PMID- 22356985
TI  - A non-photorealistic surgery simulation system.
AB  - Surgery simulation plays an important role in surgery planning, surgeon training,
      and telemedicine. A long-standing problem in this region is how to integrate
      coherent visual illustrations to deformation. In this paper, we present a new non
      photorealistic surgery simulation system that combines force visualization and
      dynamic pencil-stroke illustration. We estimate the elastic force field in real
      time and integrate it with the contact force to form a combined force map. Then,
      our rendering module is able to dynamically compute the principal directions on
      deforming organ models and apply color coded, pencil-style strokes onto the model
      for illustrating deformations. We implement these modules on GPU using NVidia's
      CUDA. Our system can faithfully and coherently reveal geometric deformation of
      organs under the force field.

PMID- 22356986
TI  - Investigating the muscle activities of performing surgical training tasks using a
      virtual simulator.
AB  - The objective of this study was to determine the muscle activities of upper
      extremities while performing fundamental surgical training tasks using a virtual
      simulator. Six subjects performed virtual cutting tasks and their muscle
      activities of upper extremities were measured. The results demonstrated a
      significant increase in muscle activities in both proximal and distal upper
      extremities, which are the common areas of occurrence of injury after prolonged
      practice. This study suggests that the upper trapezius and the extensor digitorum
      are essential prime movers to perform surgical training tasks. These muscles
      should be monitored for performance assessment in future studies.

PMID- 22356987
TI  - Computational fluid dynamics modeling of airflow inside lungs using heterogenous
      anisotropic lung tissue elastic properties.
AB  - The aim of this paper is to model the airflow inside lungs during breathing and
      its fluid-structure interaction with the lung tissues and the lung tumor using
      subject-specific elastic properties. The fluid-structure interaction technique
      simultaneously simulates flow within the airway and anisotropic deformation of
      the lung lobes. The three-dimensional (3D) lung geometry is reconstructed from
      the end-expiration 3D CT scan datasets of humans with lung cancer. The lung is
      modeled as a poro-elastic medium with anisotropic elastic property (non-linear
      Young's modulus) obtained from inverse lung elastography of 4D CT scans for the
      same patients. The predicted results include the 3D anisotropic lung deformation
      along with the airflow pattern inside the lungs. The effect is also presented of
      anisotropic elasticity on both the spatio-temporal volumetric lung displacement
      and the regional lung hysteresis.

PMID- 22356988
TI  - Telementoring for airway management between a far forward special operations
      location to a major medical center using inexpensive telemedicine solutions.
AB  - Critically ill patients in remote settings have limited access to specialized
      care. Telemedicine/telementoring can improve access to quality care, although VTC
      equipment is costly. This study showed that an inexpensive internet telecom
      software program can be effectively employed in the intubation training of a
      remote trainee.

PMID- 22356989
TI  - Using the Battlefield Telemedicine System (BTS) to train deployed medical
      personnel in complicated medical tasks - a proof of concept.
AB  - This work describes the use of Adobe Connect software along with algorithm
      software to provide the necessary audio visual communication platform for
      telementoring a complex medical procedure to novice providers located at a
      distant site.

PMID- 22356990
TI  - Real-time simulation of interaction between colon and endoscope for the
      colonoscopy simulation.
AB  - This paper proposes a novel simulation framework for the real-time deformation of
      the colon and endoscope using a skeleton-driven deformation method. Cylindrical
      lattices and a centerline are employed as the skeletons, and a mass-spring model
      is applied to the skeletons for the mechanics-based simulation. The centerline
      based collision detection and resolution algorithm is applied to simulate the
      interaction between the colon and endoscope. The proposed simulation framework is
      integrated with a colonoscopy simulation. Simulation results show that the
      proposed method allows real-time simulation (28 Hz) using the colon model
      composed of up to 241,440 meshes.

PMID- 22356991
TI  - Augmented reality visualization for guidance in neurovascular surgery.
AB  - In neurovascular surgery, and in particular surgery for arteriovenous
      malformations (AVMs), the surgeon maps pre-operative images to the patient on the
      operating table to aid in vessel localization and resection. This type of spatial
      mapping is not trivial, is time consuming, and may be prone to error. Using
      augmented reality (AR) we can register the microscope/camera image of the patient
      to pre-operative data in order to help the surgeon better understand the topology
      and locations of vessels that lie below the visible surface of the cortex. In
      this work we describe a prototype system, developed using open source software
      and built with off-the-shelf hardware, for AR visualization for AVM neurosurgery.
      Furthermore, we consider two visualization techniques, colour-coding and
      chromadepth, to enhance the depth perception of vessels.

PMID- 22356992
TI  - Development of a VR-based injection training system using a standardized patient.
AB  - We propose a VR based injection training system using Standardized Patient (SP)
      with an original haptic needle which can represent a haptic expression. SP is
      trained to realistically portray a real patient. In the proposed system, trainee
      can virtually puncture the SP using the haptic needle. In addition, the haptic
      needle can represent a haptic expression of needle insertion of the virtual
      anatomical model. By using the proposed system, trainee can feel virtual puncture
      as well as operating for real patient.

PMID- 22356993
TI  - AMILab software: medical image analysis, processing and visualization.
AB  - AMILab is a free software for image analysis, processing and visualization. It
      provides convenient visualization tools for 2D and 3D images and it is highly
      extensible through its own scripting language. We describe the main visualization
      features and the scripting language of AMILab. The software includes an automatic
      C++ wrapping system which permits fast development of new visualization tools and
      image processing algorithms.

PMID- 22356994
TI  - Generation of 3D ultrasound training volumes from freehand acquired data.
AB  - We are developing a low cost ultrasound training system running on a laptop in
      which the user scans a generic 3D curved surface representing the patient using a
      5 DoF sensor. A critical component of this system is the generation of ultrasound
      training image volumes, which need to cover a complete body region in order to
      provide a realistic scanning experience. This research attempts to develop
      stitching techniques to generate large global volumes from smaller overlapping
      volumes acquired using freehand techniques.

PMID- 22356995
TI  - Moving past normal force: capturing and classifying shear motion using 3D
      sensors.
AB  - In our previous research, we used clinical breast examination models instrumented
      with direct (normal) force sensors for training and assessment. A weakness of the
      normal force sensors is the ability to delineate, in detail, all of the
      performance measures we wish to understand. This study incorporated the use of
      newly developed shear force sensors to extend a framework for quantifying hands
      on performance.

PMID- 22356996
TI  - A study about coefficients to estimate the error in biomechanical models used to
      virtually simulate the organ behaviors.
AB  - In this paper, a set of coefficients commonly used in Medical Image to estimate
      the committed error comparing two images is presented, which, combined together,
      allow to determine the similarity between volumes. Furthermore, an analysis of
      the behavior of these coefficients is performed to determine those coefficients
      that better discriminate the fit error, proving that these are Jaccard
      coefficient and a modification of Hausdorff coefficient. In addition, the
      combination of both coefficients is applied to compare two given biomechanical
      models of the lamb liver.

PMID- 22356997
TI  - PleurAlert: an augmented chest drainage system with electronic sensing, automated
      alerts and internet connectivity.
AB  - We have enhanced a common medical device, the chest tube drainage container, with
      electronic sensing of fluid volume, automated detection of critical alarm
      conditions and the ability to automatically send alert text messages to a nurse's
      cell phone. The PleurAlert system provides a simple touch-screen interface and
      can graphically display chest tube output over time. Our design augments a device
      whose basic function dates back 50 years by adding technology to automate and
      optimize a monitoring process that can be time consuming and inconvenient for
      nurses. The system may also enhance detection of emergency conditions and speed
      response time.

PMID- 22356998
TI  - Utilization of a civilian academic center as a force multiplier in support of
      NATO special operations medicine - a pilot demonstration.
AB  - This work describes a NATO-university telemedicine collaboration established to
      perform a teleneurosurgery consult to assist a deployed soldier with a spinal
      cord injury.

PMID- 22357000
TI  - Visual tracking of laparoscopic instruments in a Hough space.
AB  - This paper describes an approach to tracking laparoscopic instruments based
      solely on visual information. The two edges of the linear instrument are
      identified as maxima within a scalable search window in the Hough space. For each
      new frame the window is moved according to the velocity of the instrument
      computed in the previous frame. The computational cost of the Hough transform is
      further reduced by considering only edge features inside a mask determined by the
      Hough search window. The technique has been successfully applied in sequences of
      a simulation task and a surgical procedure.

PMID- 22356999
TI  - Augmented environments for minimally invasive therapy: implementation barriers
      from technology to practice.
AB  - Augmented environments for medical applications have been explored and developed
      in an effort to enhance the clinician's view of anatomy and facilitate the
      performance of minimally invasive procedures. These environments must faithfully
      represent the real surgical field and require seamless integration of pre- and
      intra-operative imaging, surgical instrument tracking and display technology into
      a common framework centered around the patient. However, few image guidance
      environments have been successfully translated into clinical use. Several
      challenges that contribute to the slow progress of integrating such environments
      into clinical practice are discussed here in terms of both technical and clinical
      limitations.

PMID- 22357001
TI  - Design and evaluation of a medical teamwork training simulator using consumer
      level equipment.
AB  - Virtual environments (VE) are increasingly used for teamwork training purposes,
      e.g., for medical teams. One shortcoming is lack of support for nonverbal
      communication channels, essential for teamwork. We address this issue by using an
      inexpensive webcam to track the user's head and using that data for controlling
      avatar head movement, thereby conveying head gestures and adding a nonverbal
      communication channel. In addition, navigation and orientation within the virtual
      environment is simplified. We present the design and evaluation of a simulation
      framework based on a game engine and consumer-level hardware and the results of
      two user studies showing, among other results, an improvement in the usability of
      the VE and in the perceived quality of realism and communication within the VE by
      using head tracking avatar and view control.

PMID- 22357002
TI  - Direct haptic volume rendering in lumbar puncture simulation.
AB  - The preparation phase for surgical simulations often comprises the segmentation
      of patient data, which is needed for realistic visual and haptic rendering.
      Expert segmentation of 3D patient data sets can last from several hours to days.
      In this paper we introduce a direct haptic volume rendering approach for lumbar
      punctures. Preparation time spent for segmentation is much shorter and compared
      to our reference system nearly identical force output at the needle tip can be
      observed. The number of structures to be completely segmented by an expert is
      reduced from 11 to 3 tissues in abdominal data sets with 300 slices.

PMID- 22357003
TI  - Simulation of a human circulatory system.
AB  - This article describes a mathematically based human circulatory model. The model
      consists of lumped elements made of venous, arterial, peripheral, pulmonary vein
      and artery segments. A heart model is simulated using 4 chambers (left and right
      atriums and ventricles). The heart pump mechanism is operated by a simple piston
      based models for each of the chambers. The simulation consists of 19 (states)
      first order differential equations. and simulated with Matlab and Simulink. The
      simulation computes volume, flow rate and pressures in each segment.

PMID- 22357004
TI  - Tele-orthopaedics: United States Army European Regional Medical Command.
AB  - Telemedicine is the provision of medical care over long distances by way of
      videoconferencing and other communication technologies. Staff at Vilseck U.S.
      Army Clinic set up a 3-month pilot real-time tele-orthopaedic clinic to determine
      if it was feasible to extend Orthopaedic specialty care over long distances. A
      full time physician assistant was located at the patient site and an orthopaedic
      surgeon was located at the Landstuhl or Heidelberg site. Patients were initially
      evaluated by the PA. Complex consults were reviewed by the PA and Orthopaedic
      surgeon via telephone or VTC. Patients meeting possible indications for surgery
      were then scheduled for a VTC consult with a surgeon.

PMID- 22357006
TI  - Automated real time peg and tool detection for the FLS trainer box.
AB  - This study proposes a method that effectively tracks trocar tool and peg
      positions in real time to allow real time assessment of the peg transfer task of
      the Fundamentals of Laparoscopic Surgery (FLS). By utilizing custom code along
      with OpenCV libraries, tool and peg positions can be accurately tracked without
      altering the original setup conditions of the FLS trainer box. This is achieved
      via a series of image filtration sequences, thresholding functions, and Haar
      training methods.

PMID- 22357005
TI  - A prototype stimulator system for noninvasive Low Intensity Focused Ultrasound
      delivery.
AB  - A prototype Low Intensity Focused Ultrasound (LIFU) stimulator system was
      developed to evaluate non-invasive neuromodulation in a large animal model. We
      conducted a feasibility study on a Gottingen minipig, demonstrating reversible,
      targeted transcranial neuromodulation. The hypothalamus of the minipig was
      repeatedly stimulated with LIFU which evoked temporally correlated increases in
      both heart rate and blood pressure.

PMID- 22357007
TI  - Performance comparison of laryngoscopy and suction techniques in a hemorrhagic
      airway manikin simulator: direct laryngoscopy with Yankauer vs. Storz CMAC with
      attached suction tip.
AB  - Airway management of the hemorrhagic airway can be a difficult skill to master as
      trainee exposure to this difficult airway may be limited. In this study, we
      employed a hemorrhagic airway simulator along with a videolaryngoscope and the
      Storz Boedker-Doerges (BD) suction blade. These devices provided improved
      intubation performance in this model with respect to traditional direct
      laryngoscope (DL) and VL blades. This study shows that use of a hemorrhagic
      simulator could be an effective and valuable training tool in difficult airway
      intubation training.

PMID- 22357008
TI  - Nasotracheal intubation in a difficult airway using the Storz C-MAC
      Videolaryngoscope, the Boedeker Bougie endotracheal introducer, and the Boedeker
      curved forceps.
AB  - Airway management has multiple indications for nasotracheal intubation. In this
      study, we focus on its indication in difficult airways. This work describes a
      modified procedure of nasotracheal intubation using the new Storz CMAC(r)
      Videolaryngoscope, the malleable Boedeker Bougie and the curved Boedeker Forceps
      in the intubation of a difficult airway manikin.

PMID- 22357009
TI  - Perception of stiffness in laparoscopy - the fulcrum effect.
AB  - We explored how the perception of stiffness can be distorted in Minimally
      Invasive Surgery. We combined a mechanical simulator with a haptic device, and
      implemented linear springs at the tip of the simulated laparoscopic device. To
      explore the influence of mechanical advantage on perception, we set different
      values of the ratio between internal and external length of the tool. We found
      that a nonsymmetrical ratio causes bias in the perceived stiffness when novice
      tangential probing is compared to radial probing. In contrast, haptic experts did
      not show similar perceptual bias.

PMID- 22357010
TI  - Real-time human pose detection and tracking for tele-rehabilitation in virtual
      reality.
AB  - We present a real-time algorithm for human pose detection and tracking from
      vision-based 3D data and its application to tele-rehabilitation in virtual
      environments. We employ stereo camera(s) to capture 3D avatars of geographically
      dislocated patient and therapist in real-time, while sending the data remotely
      and displaying it in a virtual scene. A pose detection and tracking algorithm
      extracts kinematic parameters from each participant and determines pose
      similarity. The pose similarity score is used to quantify patient's performance
      and provide real-time feedback for remote rehabilitation.

PMID- 22357011
TI  - Step-based cognitive virtual surgery simulation: an innovative approach to
      surgical education.
AB  - BioDigital Systems, LLC in collaboration with New York University Langone Medical
      Center Department of Reconstructive Plastic Surgery has created a complex, real
      time, step-based simulation platform for plastic surgery education. These
      simulators combine live surgical footage, interactive 3D visualization, text
      labels, and voiceover as well as a high-yield, expert-approved testing mode to
      create a comprehensive virtual educational environment for the plastic surgery
      resident or physician.

PMID- 22357012
TI  - An experimental study on CHVE's performance evaluation.
AB  - Virtual reality-based training simulators, with collaborative capabilities, are
      known to improve the way users interact with one another while learning or
      improving skills on a given medical procedure. Performance evaluation of
      Collaborative Haptic Virtual Environments (CHVE) allows us to understand how such
      systems can work in the Internet, as well as the requirements for multisensorial
      and real-time data. This work discloses new performance evaluation results for
      the collaborative module of the CyberMed VR framework.

PMID- 22357013
TI  - Virtual reality paced serial assessment test for neuropsychological assessment of
      a military cohort.
AB  - The assessment and treatment of traumatic brain injury (TBI) has become a
      difficult challenge for the DoD medical health system. Clinical
      neuropsychologists are being asked to make statements regarding a soldier's
      functional skills, ability to return to active duty, and competence in tasks of
      community living. Given the increasing prevalence of blast injuries to the head,
      and the fact that many brain injuries may have no external marker of injury,
      there is need for researching innovative assessment methods in detecting blast
      related brain injury. To address these issues, two virtual reality-based Paced
      Auditory/Visual Serial Addition Tests (PA/VSAT) were developed that involve the
      participant being immersed in a Virtual Middle Eastern City as serial addition
      stimuli are presented. This study is an initial validation of the VRPASAT and
      VRPVSAT as assessments of neurocognitive functioning. When compared to the paper
      and-pencil version of the test, as well as the Automated Neuropsychological
      Assessment Metrics, the VRPASAT and VRPVSAT appear to have enhanced capacity for
      providing an indication of a participant's performance while immersed in a
      military relevant simulation.

PMID- 22357014
TI  - Virtual worlds are an innovative tool for medical device training in a simulated
      environment.
AB  - Medical infusion devices are an integral component within the delivery of
      healthcare management. The aim of this study was to develop a training simulation
      in the virtual world of Second Life for the management of adverse events
      associated with infusion devices. Forty nurses were subsequently recruited to
      participate within the simulation and assess its feasibility.

PMID- 22357015
TI  - Personal low-cost ultrasound training system.
AB  - To meet the challenge of making realistic training opportunities in medical
      ultrasound readily available, a PC based low cost personal ultrasound training
      system has been developed. The training experience is provided by scanning a
      generic, curved and compliant scan surface with a sham transducer, containing
      position and orientation sensors, while the PC displays both a virtual subject
      and a virtual transducer, along with an ultrasound image.

PMID- 22357016
TI  - Validation of three virtual reality Fundamentals of Laparoscopic Surgery (FLS)
      modules.
AB  - The Fundamentals of Laparoscopic Surgery (FLS) box trainer is the gold standard
      for development of laparoscopic technical skills however the scoring metrics
      require a trained proctor and do not allow for immediate feedback. The Lap
      MentorTM virtual-reality (LMVR) FLS tasks, with automated scoring metrics and
      haptic feedback, may be a suitable alternative. We determined the construct and
      concurrent validity of LMVR-FLS. Participants with a range of laparoscopic
      experience performed 3 FLS tasks on both simulators. The LMVR-FLS demonstrated
      moderate concurrent validity and evidence for construct validity. Further
      research is required to determine if skill acquisition on these modules is
      transferable to the operating room.

PMID- 22357017
TI  - A simple master-slave control mapping setup to learn robot-assisted surgery
      manipulation.
AB  - A simple, but yet effective application for learning and testing instrument
      manipulation of available (and future) master-slave control robot-assisted
      surgical systems has been created. As an example, the paper describes a simple
      mapping of da Vinci surgical system master-slave control with two haptic devices
      acts as the master control.

PMID- 22357018
TI  - The biodigital human: a web-based 3D platform for medical visualization and
      education.
AB  - NYU School of Medicine's Division of Educational Informatics in collaboration
      with BioDigital Systems LLC (New York, NY) has created a virtual human body
      dataset that is being used for visualization, education and training and is
      accessible over modern web browsers.

PMID- 22357019
TI  - Detail-on-demand visualization for lean understanding of lung abnormalities.
AB  - In some respects, the lung is an anatomical bog - having limited referential
      landmarks. Nonetheless, precise understanding of the abnormalities that inflict
      this organ is crucial to effective clinical diagnosis and treatment. However,
      wading interactively through a three-dimensional scan of the lung poses a visual
      quagmire to the radiologist, resulting in significant interpretive differences
      due to inter and intra observer variation. Despite the continuing progress in
      quantitative imaging, lack of unambiguous visualization with accurately, relevant
      cues severely hinders the clinical adoption of many computational tools. We
      address this unmet need through a lean visualization paradigm wherein information
      is presented hierarchically to provide an interactive macro-to-micro view of lung
      pathologies. At the macro level, the structural and functional information is
      summarized into a synoptic glyph that is readily interpreted and correlated to a
      priori known disease states. The glyphs are "patho-spatio-temporally" tagged to
      facilitate navigation through the level-of-detail scales, down to the micro level
      values in the image voxels, providing quantitative interpretation of tissue type
      and the confidence level in the quantitation. A novel volume compositing scheme
      is proposed to specify and guide to the optimal site for surgical lung biopsy.
      This intuitive, interactive interface for rapid and unambiguous navigation
      towards the clinical endpoint harnesses the power of bio-informatics technology
      to provide an efficient, clinically relevant and comprehensive summary of
      pulmonary disease, including precise location, spatial extent and intrinsic
      character.

PMID- 22357020
TI  - Learning Island: the development of a virtual reality system for the experiential
      training of stress management.
AB  - Psychological Stress occurs when an individual perceives that environmental
      demands tax or exceed his or her adaptive capacity. Following this view, that
      underlines the role of the situated experience of the patient in experiencing a
      stressor, the European Union funded Interstress project
      (http://www.interstress.eu) is exploring the possible use of the virtual
      simulation technology offered by SecondLife (http://www.secondlife.com) to
      administer a stress management experiential training. The structure of the
      environment and the contents of the course are described and discussed.

PMID- 22357021
TI  - Shader Lamps Virtual Patients: the physical manifestation of virtual patients.
AB  - We introduce the notion of Shader Lamps Virtual Patients (SLVP) - the combination
      of projector-based Shader Lamps Avatars and interactive virtual humans. This
      paradigm uses Shader Lamps Avatars technology to give a 3D physical presence to
      conversational virtual humans, improving their social interactivity and enabling
      them to share the physical space with the user. The paradigm scales naturally to
      multiple viewers, allowing for scenarios where an instructor and multiple
      students are involved in the training. We have developed a physical-virtual
      patient for medical students to conduct ophthalmic exams, in an interactive
      training experience. In this experience, the trainee practices multiple skills
      simultaneously, including using a surrogate optical instrument in front of a
      physical head, conversing with the patient about his fears, observing realistic
      head motion, and practicing patient safety. Here we present a prototype system
      and results from a preliminary formative evaluation of the system.

PMID- 22357022
TI  - STRIVE: Stress Resilience In Virtual Environments: a pre-deployment VR system for
      training emotional coping skills and assessing chronic and acute stress
      responses.
AB  - The incidence of posttraumatic stress disorder (PTSD) in returning OEF/OIF
      military personnel is creating a significant healthcare challenge. This has
      served to motivate research on how to better develop and disseminate evidence
      based treatments for PTSD. One emerging form of treatment for combat-related PTSD
      that has shown promise involves the delivery of exposure therapy using immersive
      Virtual Reality (VR). Initial outcomes from open clinical trials have been
      positive and fully randomized controlled trials are currently in progress to
      further validate this approach. Based on our research group's initial positive
      outcomes using VR to emotionally engage and successfully treat persons undergoing
      exposure therapy for PTSD, we have begun development in a similar VR-based
      approach to deliver stress resilience training with military service members
      prior to their initial deployment. The Stress Resilience In Virtual Environments
      (STRIVE) project aims to create a set of combat simulations (derived from our
      existing Virtual Iraq/Afghanistan exposure therapy system) that are part of a
      multi-episode narrative experience. Users can be immersed within challenging
      combat contexts and interact with virtual characters within these episodes as
      part of an experiential learning approach for training a range of
      psychoeducational and cognitive-behavioral emotional coping strategies believed
      to enhance stress resilience. The STRIVE project aims to present this approach to
      service members prior to deployment as part of a program designed to better
      prepare military personnel for the types of emotional challenges that are
      inherent in the combat environment. During these virtual training experiences
      users are monitored physiologically as part of a larger investigation into the
      biomarkers of the stress response. One such construct, Allostatic Load, is being
      directly investigated via physiological and neuro-hormonal analysis from specimen
      collections taken immediately before and after engagement in the STRIVE virtual
      experience.

PMID- 22357023
TI  - Developing effective serious games: the effect of background sound on visual
      fidelity perception with varying texture resolution.
AB  - Despite the benefits associated with virtual learning environments and serious
      games, there are open, fundamental issues regarding simulation fidelity and multi
      modal cue interaction and their effect on immersion, transfer of knowledge, and
      retention. Here we describe the results of a study that examined the effect of
      ambient (background) sound on the perception of visual fidelity (defined with
      respect to texture resolution). Results suggest that the perception of visual
      fidelity is dependent on ambient sound and more specifically, white noise can
      have detrimental effects on our perception of high quality visuals. The results
      of this study will guide future studies that will ultimately aid in developing an
      understanding of the role that fidelity, and multi-modal interactions play with
      respect to knowledge transfer and retention for users of virtual simulations and
      serious games.

PMID- 22357024
TI  - An online practice and educational networking system for technical skills:
      learning experience in expert facilitated vs. independent learning communities.
AB  - This study explored the activities of trainees learning technical skills using an
      educational networking tool with and without expert facilitation. Medical
      students (participants) were video-recorded practicing suturing and knot tying
      techniques and the resulting videos were uploaded to an educational networking
      site. Participants were then divided into two groups (one group containing an
      expert facilitator while the other group did not) and encouraged to comment on
      the videos within their group. We monitored the number of logins and comments
      posted and all participants completed an exit survey. There were no differences
      between the activities the two groups (p = 0.387). We conclude that the presence
      of an expert within collaborative Internet environments in not necessary to
      promote interactivity amongst the learners.

PMID- 22357025
TI  - Virtual skin biopsy with Gabor Domain optical coherence microscopy.
AB  - We report in-vivo volumetric optical coherence microscopy images of the skin,
      with resolution at the cellular level. With resolution of 2 MUm both laterally
      and axially, structures below the skin as deep as 1 mm may be imaged at various
      anatomic locations. Custom optical instrumentation was designed, built, and
      integrated to achieve this unprecedented optical imaging resolution, in three
      dimensions, at clinically feasible configuration and speed.

PMID- 22357026
TI  - Using anthropomorphic avatars resembling sedentary older individuals as models to
      enhance self-efficacy and adherence to physical activity: psychophysiological
      correlates.
AB  - The prevalence of obesity and associated health complications are currently at
      unprecedented levels. Physical activity in this population can improve patient
      outcomes. Virtual reality (VR) self-modeling may improve self-efficacy and
      adherence to physical activity. We conducted a comparative study of 30
      participants randomized to 3 versions of a 3D avatar-based VR intervention about
      exercise: virtual representation of the self exercising condition; virtual
      representation of other person exercising and control condition. Participants in
      the virtual representation of the self group significantly increased their levels
      of physical activity. The improvement in physical activity for participants in
      the visual representation of other person exercising was marginal. The
      improvement for the control group was not significant. However, the effect sizes
      for comparing the pre and post intervention physical activity levels were quite
      large for all three groups. We did not find any group difference in the
      improvements of physical activity levels and self-efficacy among sedentary,
      overweight or obese individuals.

PMID- 22357027
TI  - The benefits of Fundamentals of Laparoscopic Surgery (FLS) training on simulated
      arthroscopy performance.
AB  - Current theories of skill learning suggest that novices learn optimally in a
      simplified environment. This information can be incorporated in simulator
      designs. Our purpose was to assess whether basic visuospatial training is
      beneficial for performance on an arthroscopy model. One group of trainees
      practiced three visuomotor tasks while the other group was not given this
      opportunity. Both groups then performed three different surgical tasks on a
      simulated arthroscopy model. Practice with the visuomotor tasks enhanced
      performance on two of the tasks on the arthroscopy model. The basic navigational
      skills learned through practice transferred to the performance of arthroscopic
      surgery tasks and these skills should be included in the design of a
      comprehensive arthroscopy simulator.

PMID- 22357028
TI  - Modification of commercially available simulators to elicit decision making
      behavior.
AB  - In recent years, simulation training has emerged as an innovative method for
      decreasing error and teaching complex procedures. Simulation has also been a
      valuable tool for evaluating investigatory and analytic thinking. By adding a
      specific, clinically oriented modification to a commercially available simulator,
      we were able to elicit first-year emergency medicine resident perceptions,
      actions, and decisions.

PMID- 22357029
TI  - Introducing simulation technology to new faculty: do not let them play.
AB  - As part of our simulation-based curriculum design process, we require faculty
      instructors to formally examine and test the simulators prior to instructional
      use. This requirement is invaluable when using commercially available, mannequin
      based simulations. Our study shows that, when teaching a clinical examination
      using simulation, the clinical presentation of a commercial simulator should be
      defined based on the consensus of experienced clinicians instead of the
      commercial label.

PMID- 22357030
TI  - Clinical examination simulation: getting to real.
AB  - Verschuren and Hartog's six-stage methodology for design-oriented research is a
      process that is ideally suited to the development of artifacts that meet a
      desired outcome. We discuss the methodology and its relevance to simulation
      development for establishing a wide variety of realistic clinical breast
      examination models that can be used for assessment.

PMID- 22357031
TI  - A novel automated drug simulant recognition system for naturalistic real-time
      medical simulation.
AB  - The ability for a medical simulator to automatically recognize and respond to a
      "drug" injected during a training exercise offers powerful capabilities for
      objective assessment and real-time interaction. To address some of the
      limitations of available mannequin drug recognition systems, we developed a novel
      sensing system that recognizes an IV-injected agent based on an inherent property
      of the fluid. Our system uses varying concentrations of saline to represent
      different drugs and identification is made via conductivity measurement. The
      system also determines the volume administered and the time over which the dose
      is injected. Simulant solutions in IV bags (e.g., simulated Hextend or
      crystalloids) can be identified even if the bag is placed at a distance from the
      body. The system may offer advantages for field training exercises, as no
      external components need to be attached to the syringe or IV bag.

PMID- 22357032
TI  - BodyWindows: enhancing a mannequin with projective augmented reality for
      exploring anatomy, physiology and medical procedures.
AB  - Augmented reality offers the potential to radically extend and enhance the
      capabilities of physical medical simulators such as full-body mannequin trainers.
      We have developed a system that transforms the surface of a mannequin simulator
      into both a display screen and an input device. The BodyWindows system enables a
      user to open, size, and reposition multiple viewports onto the simulator body. We
      demonstrate a dynamic viewport that displays a beating heart. Similar viewports
      could be used to display real-time physiological responses to interventions the
      user applies to the mannequin, such as injection of a simulated drug. Viewport
      windows can be overlapping and show anatomy at different depths, creating the
      illusion of "cutting" multiple windows into the body to reveal structures at
      different depths from the surface. The developed low-cost interface employees an
      IR light pen and the Nintendo Wiimote. We also report experiments using the
      Microsoft Kinect computer vision sensor to provide a completely hand-gesture
      based interface.

PMID- 22357033
TI  - A simulation framework for tool tissue interactions in robotic surgery.
AB  - Robotic surgery is preferred over other traditional methods due to reduced
      complications and improved ergonomics for the operating surgeon. They are also a
      perfect platform for telesurgery. Automated surgery in which the robot is allowed
      to do various surgical tasks with minimal intervention is getting wider attention
      recently. In this paper, we introduce a simulation framework that can
      realistically simulate tool tissue interactions in robotic surgery, which can be
      used to design and test various control methodologies for automated surgical
      tasks. We present preliminary results from simulating a simple model of a
      surgical robot interacting with a volumetric model while performing a grasping
      and hold task.

PMID- 22357034
TI  - An optical tracking system for a microsurgical training simulator.
AB  - To achieve a high degree of immersion in medical training simulators, realistic
      and native user interfaces are needed. We implemented an optical tracking system
      in order to track original instruments for a microsurgical training simulator. In
      a marker-based setup, the forceps was equipped with markers. As a step towards a
      markerless tracking system, an approach with a partly coloured forceps is
      presented. Both methods were implemented and resulted in working real-time
      tracking modules.

PMID- 22357035
TI  - Using a smart wheelchair as a gaming device for floor-projected games: a mixed
      reality environment for training powered-wheelchair driving skills.
AB  - For children with a severe disability, such as can arise from cerebral palsy,
      becoming independent in mobility is a critical goal. Currently, however, driver's
      training for powered wheelchair use is labor intensive, requiring hand-over-hand
      assistance from a skilled therapist to keep the trainee safe. This paper
      describes the design of a mixed reality environment for semi-autonomous training
      of wheelchair driving skills. In this system, the wheelchair is used as the
      gaming input device, and users train driving skills by maneuvering through floor
      projected games created with a multi-projector system and a multi-camera tracking
      system. A force feedback joystick assists in steering and enhances safety.

PMID- 22357036
TI  - Virtual trainer for intra-detrusor injection of botulinum toxin to treat urinary
      incontinence.
AB  - Here we introduce a new virtual reality (VR) based simulation system for training
      the urological procedure of intra-detrusor botulinum toxin (Botox(r)) injections
      into the bladder. 6 cases with different bladder anatomy and 3 subtasks are
      included in the curriculum; this design is guided by several expert urologists
      according to clinical needs and experience. These virtual bladder models can be
      deformed by a cystoscope model or penetrated by a needle model. Data of location
      and dose per injection are collected during the training. After compared among
      various options, magnetic motion-tracking devices are chosen and integrated onto
      replicas of cystoscopic instruments as the VR interface for the specific
      operation. A web/database based learning management platform (LMP) is developed
      for online data access and validation studies of the training system.

PMID- 22357037
TI  - A transurethral catheter-based ultrasound system for multi-modal fusion.
AB  - Current methods of prostate cancer diagnosis and therapy rely on accurate imaging
      of the prostate using real-time ultrasound. Transurethral ultrasound (TUUS) may
      improve upon the current gold standard through improved 3D visualization and co
      registration (fusion) with CT and MRI. A prototype transurethral ultrasound
      (TUUS) catheter-based transducer array and system was developed, featuring 32
      elements with a diameter of 18F (6mm). A robust, multi-channel ultrasound
      transceiver was also developed to enable TUUS imaging using pulse-echo and
      frequency-based signal processing methods. The feasibility of a TUUS imaging
      system suitable for multi-modal image fusion and novel ultrasound signaling
      techniques was demonstrated.

PMID- 22357038
TI  - Assessing surgeon and novice force skill on a haptic stiffness simulator for
      laparoscopic surgery.
AB  - Though several simulators and training methods are available for basic
      laparoscopic skills, few have addressed force-based skills. In this work, we
      discuss a haptic simulator that renders virtual materials of different stiffness
      profiles to be used for haptic skills differentiation. A force-based task was
      designed on the simulator and the performance of surgeons and novices was
      analyzed. Results indicate that surgeons and novices differ in their ability to
      use the haptic device to reproduce target stiffness levels. This work provides an
      important step towards quantifying haptic skill metrics for the design of
      surgical skills training simulators.

PMID- 22357039
TI  - Haptic tasks for physical laparoscopic ("Box") trainers to differentiate surgeon
      skill.
AB  - In this work, we present four tasks, primarily testing haptic laparoscopic skill
      that can be simulated in a conventional box trainer. Results from examining
      expert surgeon and novice performance is presented as evidence that these tasks
      can be used for training haptic skills for laparoscopy in a box trainer.

PMID- 22357040
TI  - Assessment of laparoscopic surgical skill acquisition and retention.
AB  - Currently, a need exists for a more comprehensive understanding of the nature of
      laparoscopic surgical skill acquisition and decay; novel, objective metrics with
      which to assess these skills over time; and simulation-based training that
      supports rapid acquisition, longitudinal retention, and targeted retraining for
      sustainment of these critical and perishable skills. This pilot study examined
      traditional metrics of laparoscopic surgical skills training, as well as a novel
      motion tracking metric using an instrumented glove. Data were compared for
      PreTest, PostTest following training to specified proficiency levels, and ReTest
      following an 8-10 week retention period, as well as comparison to expert
      performance. Despite a small number of complete data sets (n=5 novice, n=1
      expert), these preliminary results demonstrate a lack of sensitivity of the
      current manual skills assessment metrics and demonstrate initial technical
      feasibility for the development of novel objective metrics based on instrumented
      glove motion tracking data.

PMID- 22357042
TI  - Haptic editing of MRI brain data.
AB  - Automated brain segmentation may leave errors which can be identified by
      comparing the location of the actual MRI voxels with reference to the
      reconstructed pial polygonal surface of the brain. Location of the segmentation
      errors can be marked by displaying color spots on the brain surface followed by
      its interactive editing, as we previously proposed. In this paper, a new haptic
      friction-based approach of identifying and correcting errors has been discussed.
      The user can feel as different friction the discrepancy along the reconstructed
      surface by moving a haptic proxy along it followed by rubbing the surface as if
      it is being polished. The proposed approach does not only limit its application
      in editing of medical data, but can also be successfully used for visually
      impaired group as this dynamic friction-based editing helps any novice user
      identify error prone area just by touching the surface.

PMID- 22357041
TI  - MRI skin segmentation for the virtual deformation of the breast under
      mammographic compression.
AB  - Breast Magnetic Resonance Image skin has similar intensity levels than dense
      tissue, and may produce segmentation errors if not managed correctly. In this
      work a novel skin segmentation method is presented and validated by experts,
      aimed to obtain as many pixels belonging to the real skin as possible. Segmented
      skin will be used to build a breast biomechanical model to register X-Ray Images
      with Magnetic Resonance Images in the future, using a virtually deformed Magnetic
      Resonance Image.

PMID- 22357043
TI  - Integration of surgical simulation in plastic surgery residency training.
AB  - BioDigital Systems, LLC in collaboration with New York University Langone Medical
      Center Department of Reconstructive Plastic Surgery has created an interactive,
      step-based latissimus musculocutaneous flap simulator. Preliminary testing of
      fourteen residents (PGY1-6) demonstrates that simulator training results in
      significant improvement in an objective assessment of surgical knowledge (p <
      0.0006, pre-training score: 81.0%, post-training score 92.7%). This study is the
      first in the field of plastic and reconstructive surgery to demonstrate objective
      improvement in surgical knowledge as a result of simulator training, suggesting
      the potential effectiveness of simulators for a panopoly of breast reconstruction
      options.

PMID- 22357044
TI  - Virtual simulation of mouse anatomy and procedural techniques.
AB  - Translational science requires the use of mouse models for the characterization
      of disease and evaluation of treatment therapies. However, often there is a lack
      of comprehensive training for scientists in the systemic and regional anatomy of
      the mouse that limits their ability to perform studies involving complex
      interventional procedures. We present our methodologies for the development,
      evaluation, and dissemination of an interactive 3D mouse atlas that includes
      designs for presenting emulation of procedural technique. We present the novel
      integration of super-resolution imaging techniques, depth-of-field interactive
      volume rendering of large data, and the seamless delivery of remote visualization
      and interaction to thin clients.

PMID- 22357045
TI  - System development for unrestrictive view and 4D shape acquisition in abdominal
      cavity operation using virtual space.
AB  - Laparoscopic surgery has been used for various areas of abdominal cavity.
      However, the laparoscope has limitation of its field of view and mobility. Our
      aim is to develop a new video camera system that acquires multiple viewpoints in
      the abdominal cavity. We designed a camera array that consisted of eight small
      camera modules. The camera array can change its shape so that it can be inserted
      into the abdominal cavity through trocar. Surgeon can change the viewpoint by
      switching camera output without physically moving the camera. Using eight
      camera's images, we also tried to reconstruct 3D textured shape of the surgery
      field.

PMID- 22357046
TI  - Conductometric catheter-mounted pressure sensor.
AB  - We are developing an in vivo pressure sensor that measures the change in
      conductance of a deformable electrolyte-filled catheter resulting from external
      pressure. The sensor design and materials are easily scaled and inexpensive. The
      compact, in vivo nature of the device may result in the compact instrumentation
      being unobtrusively affixed to the patient externally and removing the tethered
      to an external apparatus, the current practice. We describe our initial device
      construction and in vitro pressure measurements.

PMID- 22357047
TI  - THP-1 leukemia cancer treatment using a portable plasma device.
AB  - This research study examined the effect of non-thermal portable atmospheric air
      plasma system on leukemia cancer cells. Acute monocytic leukemia cells (THP-1)
      were exposed to atmospheric pressure non-thermal plasma. To assess death caused
      by plasma exposure, cells were subjected to trypan blue exclusion assays and a
      kill-curve and assessment of death overtime were compiled using data from the
      assays. In addition to this, DNA was harvested from treated and untreated samples
      to determine if apoptotic ladders were present. Results have indicated that non
      thermal plasma can cause cell death in THP-1 cells overtime, and the death that
      occurs corresponds directly to the amount of time that the cells were exposed to
      ionized plasma. Preliminary fluorescent imaging of the treated cells revealed
      that higher treatment doses are not only more likely to induce cellular death but
      are likely to induce necrotic death, while lower treatment doses that are capable
      of inducing death may induce apoptotic or programmed cellular death. Ideally the
      results obtained from these experiments will allow for further investigation of
      the effects of ionized non-thermal plasma on melanoma cell lines and will lead to
      an inexpensive method for treating early stage skin cancer and cancerous lesions.

PMID- 22357048
TI  - Portable plasma medical device for infection treatment.
AB  - The purpose of this study was to determine the effects of plasma treatment on
      bacteria in liquid phases. We predict that the plasma gas can penetrate the
      liquid culture media and plasma treatment will efficiently kill the bacteria at
      unique time and distance parameters. It is also hypothesized that less stringent
      plasma treatment will negatively affect the growth rate of some species of
      bacteria and possibly their pathogenicity. The bacteria were exposed to hot and
      cold plasma at various time lengths and distance parameters. Our results
      indicated that 2 minutes of hot plasma treatment with the plasma torch 5 cm away
      from the liquid culture is effective in killing/sterilizing cultures of S.
      aureus, S. pyogenes, Salmonella spp, N. meningitidis, and E. coli. Five minutes
      of cold plasma with the probe immersed 1-2 cm inside the liquid culture were
      needed to kill the bacteria. The portable nonthermal plasma system can be used
      for infection treatment and wound healing applications affected by the microbes
      studied in this research.

PMID- 22357049
TI  - 3DUI assisted lower and upper member therapy.
AB  - 3DUIs are becoming very popular among researchers, developers and users as they
      allow more immersive and interactive experiences by taking advantage of the human
      dexterity. The features offered by these interfaces outside the gaming
      environment, have allowed the development of applications in the medical area by
      enhancing the user experience and aiding the therapy process in controlled and
      monitored environments. Using mainstream videogame 3DUIs based on inertial and
      image sensors available in the market, this work presents the development of a
      virtual environment and its navigation through lower member captured gestures for
      assisting motion during therapy.

PMID- 22357050
TI  - The effects of a mobile stress management protocol on nurses working with cancer
      patients: a preliminary controlled study.
AB  - Oncology nurses face extraordinary stresses that may lead to emotional
      exhaustion, a feeling of emotional distance from patients and burnout. The
      presentation describes the preliminary results of a study to test the effects of
      an innovative 4-week 8-session self-help stress management training for oncology
      nurses supported by mobile tools (Nokia N70 smarthphone). The sample included 16
      female oncology nurses with permanent status employed in different oncology
      hospitals in Milan, Italy. The study used a between-subjects design, comparing
      the experimental condition (mobile phone stress management protocol) with a
      control group (neutral videos through mobile phones). In addition to a
      significant reduction in anxiety state at the end of each session, the
      experimental group demonstrated a significant improvement in affective change in
      terms of anxiety trait reduction and coping skills acquisition at the end of the
      protocol.

PMID- 22357051
TI  - A method to compute respiration parameters for patient-based simulators.
AB  - We propose a method to automatically tune a patient-based virtual environment
      training simulator for abdominal needle insertion. The key attributes to be
      customized in our framework are the elasticity of soft-tissues and the
      respiratory model parameters. The estimation is based on two 3D Computed
      Tomography (CT) scans of the same patient at two different time steps. Results
      are presented on four patients and show that our new method leads to better
      results than our previous studies with manually tuned parameters.

PMID- 22357052
TI  - A comparison of an integrated suction blade versus a traditional
      videolaryngoscope blade in the endotracheal intubation of a hemorrhagic cadaver
      model - a pilot study.
AB  - In this pilot study, we evaluated two types of videolaryngoscope blades
      (integrated suction vs. traditional) with the Storz CMAC videolaryngoscope in the
      intubation of a lightly embalmed hemorrhagic cadaver model. No significant
      differences were found between the devices in the success rates for the
      intubations. The study subjects indicated a preference for the integrated suction
      blade in hemorrhagic airway intubation.

PMID- 22357053
TI  - Use of a malleable bougie and curved forceps with videolaryngoscopy in airway
      management training in a cadaver model - a pilot study.
AB  - The wider angle of view of videolaryngoscopy versus standard direct laryngoscopy
      requires an assessment of the adjunctive devices used to facilitate intubation.
      In this study, subjects performed malleable bougie-assisted intubation and curved
      forceps removal of a glottic foreign body using videolaryngoscopy on a lightly
      embalmed cadaver and completed a post-procedure questionnaire. All subjects
      valued access to the malleable bougie available at their hospitals and 82% valued
      access to the curved forceps. Malleable bougie and curved forceps seem well
      suited to facilitate videolaryngoscopic airway management.

PMID- 22357054
TI  - Virtual intubation training at a remote military site.
AB  - To provide medical support to the far forward battlefield, training in advanced
      medical technologies is essential for military healthcare providers. To meet this
      challenge, the use of modern video communication technologies and novel medical
      devices can be implemented. This study demonstrates the combined use of modern
      video conferencing technology and video laryngoscopy equipment in the virtual
      laryngoscopy training of deployed military medical personnel.

PMID- 22357055
TI  - Translating surgical metrics into automated assessments.
AB  - In the effort to promote more continuous and quantitative assessment of surgical
      proficiency, there is an increased need to define and establish common surgical
      metrics. Furthermore, as various pressures such as limited duty hours and access
      to educational resources, including materials and expertise, place increased
      demands on training, the value of quantitative automated assessment becomes
      increasingly apparent. We present our methods to establish common surgical
      metrics within the otology and neurotology community and our initial efforts in
      the subsequent transfer of these metrics into objective automated assessments
      provided via a simulation environment.

PMID- 22357056
TI  - Three-dimensional micro-imaging (MUCT) based physical anatomic teaching models:
      implementation of a new learning aid for routine use in anatomy lectures.
AB  - The aim of our project is the development and implementation of MUCT based
      plastic anatomical models to make them commercially available as an anatomy
      learning tool for students at all levels. High resolution MUCT of human ossicles
      and trabecular bone was performed. After image processing, application of rapid
      prototyping and rapid manufacturing technologies, enlarged physical teaching
      models, magnified by a factor of 20, were built and provided an accurate
      representation of the human anatomy.

PMID- 22357057
TI  - A voice-based automated system for PTSD screening and monitoring.
AB  - Comprehensive evaluation of PTSD includes diagnostic interviews, self-report
      testing, and physiological reactivity measures. It is often difficult and costly
      to diagnose PTSD due to patient access and the variability in symptoms presented.
      Additionally, potential patients are often reluctant to seek help due to the
      stigma associated with the disorder. A voice-based automated system that is able
      to remotely screen individuals at high risk for PTSD and monitor their symptoms
      during treatment has the potential to make great strides in alleviating the
      barriers to cost effective PTSD assessment and progress monitoring. In this paper
      we present a voice-based automated Tele-PTSD Monitor (TPM) system currently in
      development, designed to remotely screen, and provide assistance to clinicians in
      diagnosing PTSD. The TPM system can be accessed via a Public Switched Telephone
      Network (PSTN) or the Internet. The acquired voice data is then sent to a secure
      server to invoke the PTSD Scoring Engine (PTSD-SE) where a PTSD mental health
      score is computed. If the score exceeds a predefined threshold, the system will
      notify clinicians (via email or short message service) for confirmation and/or an
      appropriate follow-up assessment and intervention. The TPM system requires only
      voice input and performs computer-based automated PTSD scoring, resulting in low
      cost and easy field-deployment. The concept of the TPM system was supported using
      a limited dataset with an average detection accuracy of up to 95.88%.

PMID- 22357058
TI  - A decision fusion strategy for polyp detection in capsule endoscopy.
AB  - Wireless capsule endoscopy (CE) is now routinely used for non-invasive diagnosis
      of small bowel diseases. But, it still requires manual assessment of the
      approximately 50,000 study images. Literature has recently investigated automated
      methods to detect and analyze various anomalies in CE images to improve reading
      efficiency and reduce variability. We propose such a computer aided diagnosis
      (CAD) approach to detect small bowel polyps. For supervised classification of
      polyps, we investigated fusing multiple statistical classifiers based on color,
      texture and edge features. The combined boosted classifier when evaluated using
      1200 CE images outperformed all individual classifiers and achieved a ~90%
      classification accuracy.

PMID- 22357062
TI  - Effects of cell storage and passage on basal and oxytocin-regulated prostaglandin
      secretion by equine endometrial epithelial and stromal cells.
AB  - Cell cultures are useful for determining the responses of specific cell types to
      various factors under controlled conditions and for obtaining a better
      understanding of in vivo physiologic processes. The aims of the present study
      were (i) to establish methodologies for isolation, culture and cryopreservation
      of equine endometrial epithelial and stromal cells; and (ii) to determine the
      effect of passage and cryopreservation on endometrial cell physiology, based on
      their basal and oxytocin (OT)-stimulated prostaglandin (PG) release. Epithelial
      and stromal cells were obtained by enzymatic digestion of equine endometrium
      collected from Days 2-5 of the estrous cycle (n = 16). Primary epithelial and
      stromal cells, as well as cryopreserved cells were stimulated with OT (10(-7)m)
      for 24 h. The concentrations of PGE(2) and PGF(2alpha) in the culture medium were
      measured by enzyme-linked immunosorbent assay (EIA). Oxytocin increased PGE(2)
      and PGF(2alpha) release by primary cultures of unfrozen epithelial cells until
      passage I (P < 0.01) and by the primary culture of unfrozen and
      cryopreserved/thawed stromal cells until passage IV (P < 0.01).
      Cryopreserved/thawed stromal cells cultured up to passage IV and unfrozen
      epithelial cells derived from passage I have physiological properties similar to
      those observed in primary culture and may be successfully used for in vitro
      studies of PG secretion.

PMID- 22357063
TI  - [Social inequalities in health: bad times for poetry].

PMID- 22357064
TI  - Clinical significance of night-to-night sleep variability in insomnia.
AB  - OBJECTIVES: To evaluate the clinical relevance of night-to-night variability of
      sleep schedules and insomnia symptoms. METHODS: The sample consisted of 455
      patients (193 men, mean age=48) seeking treatment for insomnia in a sleep
      medicine clinic. All participants received group cognitive behavioral therapy for
      insomnia (CBTI). Variability in sleep parameters was assessed using sleep diary
      data. Two composite scores were computed, a behavioral schedule composite score
      (BCS) and insomnia symptom composite score (ICS). The Insomnia Severity Index,
      the Beck Depression Inventory, and the Morningness-Eveningness Composite Scale
      were administered at baseline and post-treatment. RESULTS: Results revealed that
      greater BCS scores were significantly associated with younger age, eveningness
      chronotype, and greater depression severity (p<0.001). Both depression severity
      and eveningness chronotype independently predicted variability in sleep schedules
      (p<0.001). Finally, CBTI resulted in reduced sleep variability for all sleep
      diary variables except bedtime. Post-treatment symptom reductions in depression
      severity were greater among those with high versus low baseline BCS scores
      (p<0.001). CONCLUSIONS: Results suggest that variability in sleep schedules
      predict reduction in insomnia and depressive severity following group CBTI.
      Schedule variability may be particularly important to assess and address among
      patients with high depression symptoms and those with the evening chronotype.

PMID- 22357065
TI  - Enumeration of Mycobacterium avium subsp. paratuberculosis by quantitative real
      time PCR, culture on solid media and optical densitometry.
AB  - BACKGROUND: Different approaches are used for determining the number of
      Mycobacterium avium subsp. paratuberculosis (MAP) cells in a suspension. The
      majority of them are based upon culture (determination of CFU) or
      visual/instrumental direct counting of MAP cells. In this study, we have compared
      the culture method with a previously published F57 based quantitative real-time
      PCR (F57qPCR) method, to determine their relative abilities to count the number
      of three different MAP isolates in suspensions with the same optical densities
      (OD). McFarland turbidity standards were also compared with F57qPCR and culture,
      due to its frequent inclusion and use in MAP studies. FINDINGS: The numbers of
      MAP in two-fold serial dilutions of isolates with respective OD measurements were
      determined by F57qPCR and culture. It was found that culture provided lower MAP
      CFU counts by approximately two log10, compared to F57qPCR. The McFarland
      standards (as defined for E. coli) showed an almost perfect fit with the
      enumeration of MAP performed by F57qPCR. CONCLUSIONS: It is recommended to use
      culture and/or qPCR estimations of MAP numbers in experiments where all
      subsequent counts are performed using the same method. It is certainly not
      recommended the use of culture as the standard for qPCR experiments and vice
      versa.

PMID- 22357066
TI  - Building evidence for practice:  not without dissemination.

PMID- 22357067
TI  - Are breast milk banks a real solution yet?

PMID- 22357069
TI  - In-hospital survival skills training for type 1 diabetes: perceptions of children
      and parents.
AB  - PURPOSE: When a child is diagnosed with type 1 diabetes, parents and/or children
      must gain significant knowledge and learn specific skills to maintain health.
      Children in the United States who experience diabetic ketoacidosis (DKA) at the
      time of diagnosis typically spend 3 days in the hospital learning these life
      saving skills. The purpose of this study was to gain knowledge concerning
      children's and parents' perceptions of this hospitalization period and of the
      initial education and support received from nurses. STUDY DESIGN AND METHODS: The
      study used qualitative descriptive methods. A child interview guide and written
      parent survey were used to elicit children's and parents' perceptions. Two
      outside experts reviewed these tools. Twenty children aged 8 to 15 years along
      with 25 parents participated. Reductionistic and constructionistic steps were
      used to analyze the qualitative data. RESULTS: During this hospitalization,
      children were most disturbed by the invasiveness of the required interventions
      while parents reported significant emotional distress related to the diagnosis.
      Children and parents alike felt the Survival Skills Training they received was
      effective. Education involving demonstration and return demonstration,
      supervision of skill performance, positive feedback from nurses about skill
      performance, and reassurance for long-term quality of life were nurse behaviors
      found to be helpful. CLINICAL IMPLICATIONS: Implications for care include age
      appropriate information in a variety of formats, minimizing the invasive nature
      of the treatment, providing opportunities for demonstration/return demonstration
      of skills, providing positive support and reassurance, and delivering
      concentrated instruction related to carbohydrate counting.

PMID- 22357070
TI  - Transition to home after neonatal surgery for congenital heart disease.
AB  - PURPOSE: To ascertain the primary caregiver's postdischarge perceptions of infant
      care issues after neonatal heart surgery. STUDY DESIGN AND METHODS: Fifteen
      primary caregivers of infants who had neonatal heart surgery for complex
      congenital heart disease (CHD) participated in this study. We conducted two focus
      groups and four individual phone interviews using a structured interview guide.
      The topics included parent feeding management, infant caloric intake, parental
      acceptance of nasogastric tube, infant feeding behaviors, and issues of parenting
      stress. We audio recorded focus group sessions, made detailed notes and key
      quotes were recorded verbatim by a certified impartial focus group facilitator.
      RESULTS: Feeding problems were present in both infants who were on full oral
      feeds and infants who were dependent on supplemental feeding tubes. Mothers of
      infants with feeding problems expressed concern over infant weight gain and
      caregiver sleep deprivation, which largely contributed to parental stress.
      CLINICAL IMPLICATIONS: In this small study of infants who experienced neonatal
      surgery for complex CHD, parental stress over feeding and weight gain were
      identified as important areas to be addressed during hospitalization. Future
      studies are needed to address increased at-home parental support.

PMID- 22357072
TI  - Maternal obesity: improving pregnancy outcomes.
AB  - Approximately 30% of pregnant women are obese (body mass index [BMI] >= 30) and
      are at risk for adverse pregnancy outcomes. In this article, we review the
      literature on select obstetrical risks associated with maternal obesity and
      assess the recommended prevention and management strategies. The selected risks
      include infertility, fetal anomalies, gestational hypertensive diseases,
      gestational diabetes, intrauterine fetal death, cesarean birth, macrosomia, and
      long-term risks of adult disease for the fetus. The causes of these adverse
      outcomes include maternal body habitus, the proinflammatory state of obesity, and
      metabolic dysfunction. We also discuss how nurses, nurse practitioners, and nurse
      midwives can make a difference in the prenatal care and immediate pregnancy
      outcomes of pregnant women with obesity and influence future health for these
      women and their children.

PMID- 22357073
TI  - Treating polycystic ovary syndrome and infertility.
AB  - Between 4% and 18% of women worldwide are affected by polycystic ovary syndrome
      (PCOS) and have the hormonal imbalances that lead to the cascade of symptoms,
      including weight gain and obesity. One of the first suggested treatments for
      infertility associated with PCOS is weight reduction, which has been shown to
      increase the chance of spontaneous ovulation and menstruation. Pharmacologic
      treatment usually includes metformin alone or in conjunction with clomiphene;
      both have been shown to increase conception rates and decrease risk of
      preeclampsia once pregnancy is achieved. Limited research has been published
      about the efficacy of oral contraceptives in producing conception. If pregnancy
      still eludes women with PCOS after initial pharmacologic treatments, gonadotropin
      therapy by itself or in conjunction with assisted reproductive therapy is
      considered. These treatments come with higher expense, and increased risk, and
      require extensive counseling prior to implementation. Additional research is
      needed to better understand what risks exist for pregnant women with PCOS and for
      their newborns.

PMID- 22357075
TI  - Starting college: a critical time for weight gain.

PMID- 22357074
TI  - Does a satisfactory relationship with her mother influence when a 16-year-old
      begins to have sex?
AB  - PURPOSE: To examine aspects of the mother-daughter relationship as perceived by
      the 16-year-old (cohesion, flexibility, communication, monitoring, and
      satisfaction with time spent together) as they relate to when the daughter began
      having sex. METHODS: A secondary analysis using data from the National
      Longitudinal Survey of Youth Child (1992-2000) and Young Adult (1996-2004)
      surveys were analyzed (N = 1,592). Logistic regression models estimated reports
      of cohesion, flexibility, communication, monitoring, and satisfaction with time
      spent together with sexual initiation by age 16. All models controlled for the
      mother's sociodemographic characteristics, lack of independence due to sisters in
      the sample, and extended time away from mother. RESULTS: Girls who reported being
      satisfied with the amount of time spent with their mother were less likely to
      report early sexual initiation. In addition, these girls were three times more
      likely to report good communication and four times more likely to report high
      levels of cohesion with their mothers. Individually, in addition to satisfaction
      with time spent together, high levels of cohesion and good communication were
      also associated with lower reports of sexual initiation by age 16. CLINICAL
      IMPLICATIONS: The feeling of being satisfied with the time spent together appears
      to be a global measure of the individual dimensions of cohesion and
      communication. Efforts in delaying sexual initiation in adolescents need to be
      directed at the mother-daughter relationship. Interventions to develop these
      dimensions within the relationship during early adolescence, as compared to
      interventions when sexual activity may have already occurred, are warranted.

PMID- 22357076
TI  - Social networking principles for nurses.

PMID- 22357078
TI  - The Mobile Obstetric Maternal (MOM) Health Workers Project: improving maternal
      and newborn health in Eastern Burma.

PMID- 22357079
TI  - New guidance on the timing of medically indicated births before 39 weeks
      gestation.

PMID- 22357080
TI  - Locked plating of periprosthetic femur fractures above total knee arthroplasty.
AB  - BACKGROUND: Fractures of the femur above a total knee arthroplasty (TKA) are
      becoming increasingly common in the osteoporotic, aging populations of developed
      countries. Treatment of these fractures is complicated by the presence of a knee
      prosthesis, frequently limiting the bone available for distal fracture fixation.
      The recent application of minimally invasive surgical techniques and locked plate
      technology to this problem offers the promise of stable, fixed-angle fixation of
      small distal fracture fragments with limited surgical exposure. The purpose of
      this study is to report the clinical and radiographic outcomes of fracture
      fixation using this technique in patients with periprosthetic femur fractures
      above TKA. METHODS: Fifty-three patients presenting with periprosthetic femur
      fractures above a TKA were treated with osteosynthesis. One patient was lost to
      follow-up resulting in 52 patients with complete data. Thirty-four patients were
      treated with plate fixation and 18 patients underwent retrograde intramedullary
      nail fixation (RIMN). Using a comprehensive electronic medical record, we
      recorded data regarding patient-related demographics, nature of the fractures,
      the operative treatment, and clinical and radiographic outcomes for all patients
      treated with osteosynthesis. RESULTS: Successful fracture healing occurred in 75%
      of patients (39 of 52). Mean operating time was 91.6 +/- 6.8 minutes in the RIMN
      group and 87.4 +/- 6.4 minutes in the locked plating (LP) group (P = 0.46). Mean
      intraoperative blood loss was 182 +/- 31.6 mL in the RIMN group and 177.5 +/-
      23.4 mL in the LP group (P = 0.91). The mean time to bone union was 3.7 +/- 0.30
      months in the RIMN group and 4.0 +/- 0.27 months in the LP group (P = 0.95). The
      most common cause of treatment failure was patient death within 6 months (9
      patients [17%]); three of 18 were treated with a nail and 6 of 34 with a plate (P
      = 1.0). In the LP group, three (9%) sustained fracture nonunions, three (9%)
      sustained fracture malunions, and two (6%) sustained surgical site infections. In
      the RIMN group, one (6%) failed to unite as a result of infection and two (11%)
      developed fracture malunions. There were no significant differences between
      patients treated with LP and those treated with RIMN. CONCLUSIONS: Despite
      significant advances in surgical technique and implant design, the treatment of
      periprosthetic femur fractures above a TKA remains a challenge. LP using an
      indirect reduction technique is applicable to most patients and prosthetic
      designs and can provide similar favorable results as compared with treatment with
      a RIMN in periprosthetic femoral fractures. LEVEL OF EVIDENCE: Therapeutic Level
      III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22357081
TI  - Anterior pelvic external fixator versus subcutaneous internal fixator in the
      treatment of anterior ring pelvic fractures.
AB  - OBJECTIVES: To compare the short-term results of anterior pelvic external
      fixation (APEF) versus anterior pelvic internal fixation (APIF) applied
      subcutaneously in the context of surgical treatment of pelvic ring injuries.
      DESIGN: A single center retrospective chart review. SETTING: A level 1 trauma
      center. METHODS: A consecutive series of 48 patients who underwent surgical
      stabilization of their anterior pelvic ring (24 utilizing APIF and 24 utilizing
      APEF) by 2 surgeons at a single hospital were studied. The choice to use either
      APEF or APIF was left up to each surgeon, the indications for use are the same.
      Data collected included surgical or postoperative complications including
      infection, implant failure, reoperation, documented surgical site pain persisting
      to clinical follow-up visits, and radiographic union. Measurements on inlet and
      outlet pelvic radiographs were made immediately postoperation and at all follow
      up clinic visits to determine whether there were differences in maintaining
      pelvic fracture reduction. Statistical analysis was performed to evaluate
      significant differences between the 2 groups with regard to each of these
      variables. RESULTS: The APIF group was found to have a significantly lower
      incidence of wound complication (P < 0.05) and a lower occurrence of associated
      morbidity events as compared with the APEF group. In addition, the APIF group was
      found to have a significantly lower rate of surgical site pain persisting through
      all clinical follow-up intervals (P = 0.05). There was no difference between the
      2 groups in terms of maintenance of pelvic reduction in the early postoperative
      phase or at final follow-up. No other significant differences were observed
      between the 2 groups. CONCLUSIONS: The present study, which was based on our
      initial experience with the subcutaneous anterior pelvic fixator, demonstrated
      encouraging clinical outcomes in terms of a lower wound complication rate and
      associated morbidity, and surgical site symptoms, although maintaining equivalent
      reduction. These findings suggest that further analysis of this technique is
      warranted to determine if it can be definitively recommended for general use.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 22357082
TI  - Grand rounds from Vanderbilt University: 3-part proximal humerus fracture.

PMID- 22357083
TI  - Grand rounds from Vanderbilt University: distal femoral fracture.

PMID- 22357084
TI  - The functional consequence of syndesmotic joint malreduction at a minimum 2-year
      follow-up.
AB  - OBJECTIVE: To examine the correlation between syndesmotic malreduction and
      functional outcome. DESIGN: Prospective evaluation of bilateral computed
      tomography scans and functional outcome scores. SETTING: Level I regional trauma
      center. MATERIALS AND METHODS: From January 1, 2004, to December 31, 2006, 107 of
      681 operatively treated ankle fractures (15.7%) had associated syndesmotic
      injuries requiring reduction and fixation. All patients available at a minimum of
      2 years postindex procedure underwent clinical and radiographic examination,
      computed tomographic (CT) scanning of both ankles (injured and uninjured), and
      functional outcome scoring using the Short Form Musculoskeletal Assessment and
      Olerud/Molander questionnaires. RESULTS: Sixty-eight of 107 (63.5%) syndesmotic
      injuries in 68 patients were available for follow-up. Twenty-seven (39%) were
      malreduced (rotational or translational asymmetry) when compared with the
      contralateral uninjured syndesmotic joint. Fifteen percent of the open
      syndesmotic reductions were malreduced on postoperative CT scans, whereas 44%
      (A/B) of the closed syndesmotic reductions were malreduced on postoperative CT
      scan (P = 0.11). Patients with a malreduced syndesmosis recorded significantly
      worse functional outcome scores (P < 0.05) on both the Short Form Musculoskeletal
      Assessment and Olerud/Molander questionnaires when compared with those patients
      whose syndesmosis had healed in anatomic alignment. CONCLUSIONS: At a minimum of
      2 years follow-up, patients with malreduced syndesmotic injuries demonstrated
      significantly worse functional outcome using the Short Form Musculoskeletal
      Assessment and Olerud/Molander questionnaires. Open reduction of the syndesmosis
      resulted in a substantially lower rate of malreduction when evaluated by
      postoperative CT scan. Based on these findings, we recommend that surgeons not
      only perform a direct, open visualization of the syndesmosis during the reduction
      maneuver, but obtain a postoperative CT scan with comparison to the contralateral
      extremity as well. If the syndesmosis is found to be malreduced, consideration
      must be given to revising the osteosynthesis. LEVEL OF EVIDENCE: Prognostic Level
      II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22357085
TI  - Gunshot wounds to the acetabulum.
AB  - OBJECTIVES: To classify the fracture patterns of gunshot wounds to the
      acetabulum; identify the associated injuries and complications; determine the
      predictors of poor outcome and deep infection; and propose a treatment algorithm
      based on the results. DESIGN: Retrospective review of two trauma registry
      databases over a 13-year period. SETTING: Multicenter study. PATIENTS: Thirty
      nine gunshot wounds to the acetabulum (38 patients). INTERVENTION: Treatment
      strategy was based on infection control by treating bowel and bladder injury,
      presence/absence of intra-articular lead, pattern, and stability of the fracture.
      MAIN OUTCOME MEASUREMENTS: Merle d'Aubigne score, rate of failures, and
      complications. Multivariate logistic regression analysis to detect predictors of
      poor outcome and deep infection. RESULTS: There were 32 simple (82%) and seven
      (18%) associated fracture patterns. Bowel injuries were the most common
      associated injures. There was a 54% major complication rate. Significant
      predictors of poor outcome were high-velocity missile, involvement of the
      acetabular dome, abdominal injury, nerve injury, vascular injury, and male
      gender. Significant factors associated with deep infection were presence of a
      bowel injury with primary anastomosis of the bowel and an associated fracture
      pattern. CONCLUSIONS: The Letournel classification system can be applied to
      describe these injuries. The successful treatment of the bowel injury directly
      correlates to infection control. Diverting colostomy is associated with a
      reduction of the infection rate. Overall, gunshot wounds to the acetabulum are
      catastrophic injuries with a high complication rate and poor functional outcome.
      A multidisciplinary algorithm is proposed for treatment of these complex
      injuries. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 22357087
TI  - Propensity for hip dislocation in gait loading versus sit-to-stand maneuvers:
      implications for redefining the dome of the acetabulum needed for stability of
      the hip during activities of daily living.
AB  - INTRODUCTION: Current recommendations relating to the treatment of acetabular
      fractures are based on studies that evaluate the loading patterns associated with
      normal gait despite the fact that the forces on the acetabulum are significantly
      greater during sit-to-stand activities. We hypothesize that this increased force
      will lead to greater instability when an acetabular fracture occurs, and our goal
      was to compare cadaveric hip stability during single-leg-stance (SLS) and sit-to
      stand (STS) maneuvers using a transverse acetabular fracture model. METHODS:
      Seven fresh-frozen cadaveric hemipelvic specimens with proximal femurs were
      dissected of all soft tissues. Transverse acetabular osteotomies were created in
      5-mm increments from distal to proximal. The roof arc angle and decrease of
      articular surface area were measured after each osteotomy, and the specimens were
      tested in SLS and STS. A 1200-N load was applied and visible dislocation was
      recorded for each loading orientation. RESULTS: The average roof arc angle needed
      to dislocate in the SLS position was 46.1 degrees  in the anteroposterior, 71.9
      degrees  in the iliac oblique, and 25.2 degrees  in the obturator oblique views
      compared with 90.9 degrees  in anteroposterior, 101.4 degrees  in iliac oblique,
      and 67.3 degrees  in obturator oblique views for the STS orientation (P < 0.003
      for all radiographic views). The decrease in articular surface area needed to
      dislocate the hip was significantly less for the STS group (10.9%) than the SLS
      group (36.4%) (P = 0.003). CONCLUSIONS: There is significantly greater hip
      instability seen with STS loading of a transverse acetabular model than with
      simple SLS loading. This would suggest that some fractures previously deemed
      stable may show significant instability during common activities of daily living,
      and reassessment of nonoperative treatment may be indicated.

PMID- 22357088
TI  - Surgical management of posterior hip dislocations associated with posterior wall
      acetabular fracture:  a study with a minimum follow-up of 15 years.
AB  - OBJECTIVES: To evaluate the long-term outcome after surgical management of
      posterior hip dislocations associated with posterior wall acetabular fracture and
      to depict prognostic factors that may affect surgical results. DESIGN:
      Retrospective review. SETTING: Level I trauma center. PATIENTS AND METHODS:
      Between 1983 and 1991, 19 patients with traumatic posterior hip dislocation
      associated with posterior wall fracture of the acetabulum were retrospectively
      reviewed. The clinical criteria proposed by Merle d'Aubigne were used for the
      evaluation of the patient's clinical status. Matta's radiologic scoring system
      was used for the analysis of the radiologic data. The Brooker scoring system was
      used to assess the extent of heterotopic ossification after acetabular fracture
      surgery. RESULTS: There were 17 male patients and two female. The age range at
      the time of injury was 16 to 54 years with a mean age of 36 years. Follow-up
      ranged from 15 to 23 years (mean, 18.5 years). At final follow-up, radiographic
      outcomes were excellent in six patients (31.58%), good in 11 (57.89%), and fair
      in two (10.53%) patients. The mean clinical score was 15, ranging from 9 to 18.
      Clinical outcome was excellent in 10 cases (52.63%), good in six cases (31.58%),
      and fair in three cases (15.79%). When an anatomic reduction was achieved
      intraoperatively, excellent or good radiographic and clinical results were shown
      in 100% and 87.50% of the patients, respectively. CONCLUSION: The adequacy of
      surgical reduction will determine the long-term outcome of surgically managed
      posterior hip dislocations associated with posterior wall acetabular fracture.
      LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 22357089
TI  - Use of temporary partial intrailiac balloon occlusion for decreasing blood loss
      during open reduction and internal fixation of acetabular and pelvis fractures.
AB  - Patients with pelvic and/or acetabular fractures can sustain significant blood
      loss at the time of their injury and during surgery. We report on the technique,
      effect on blood loss, and complications with the use of temporary partial
      intrailiac balloon occlusion during open reduction and internal fixation of
      pelvic and acetabular fractures in a series of patients refusing allogeneic blood
      products for philosophical or religious reasons. An intra-arterial balloon is
      positioned in the common iliac artery immediately preoperatively, ipsilateral to
      the fracture in the interventional radiography suite. This balloon is then
      periodically inflated and deflated throughout the case by the anesthesiologist to
      mitigate operative blood loss. For anterior approaches, average blood loss was
      significantly less for those patients operated with temporary partial intrailiac
      balloon occlusion compared with those without. For posterior approaches, blood
      loss was not significantly different. One complication occurred in a patient who
      developed an arterial thrombus requiring surgical removal by the vascular surgery
      service at the conclusion of the orthopaedic surgery. He had no further sequelae.
      Although not recommended for routine use in all pelvic and acetabular fractures,
      we feel the use of temporary partial intrailiac balloon occlusion merits further
      study and may be beneficial in reducing blood loss during anterior pelvic or
      acetabular procedures in those patients who are opposed to allogeneic blood
      products and cell saver or those who cannot tolerate an anticipated massive blood
      loss.

PMID- 22357090
TI  - Central head perforation, or "cut through," caused by the helical blade of the
      proximal femoral nail antirotation.
AB  - OBJECTIVE: This study was designed to investigate the specific type and incidence
      of implant failure in patients with a proximal femur fracture treated with a
      proximal femoral nail antirotation. This device has a helical-shaped blade as a
      neck-head holding device, instead of the lag screw used in other intramedullary
      nails. The advantage of the blade is believed to originate from bone impaction
      and a larger bone-implant interface in comparison with the lag screw design, with
      consequential greater mechanical resistance to torsion in the cancellous bone.
      PATIENTS AND METHODS: This is a retrospective cohort study conducted at the state
      hospital of Winterthur, Switzerland. From December 2006 until November 2008, 210
      consecutive patients were treated with a pertrochanteric femur fracture (OTA type
      31-A1, 31-A2, and 31-A3) using a proximal femoral nail antirotation. One hundred
      and twelve patients were followed up clinically for a minimum of 12 months after
      discharge. Clinical and radiologic assessment of fracture healing and/or implant
      failure was investigated. RESULTS: We report 7 cases of implant failure with a
      "Cut Through," defined as a postoperative central perforation of the spiral blade
      into the hip joint, without any displacement of the neck-head fragment.
      CONCLUSIONS: Cut through needs to be distinguished from the well-known
      anterocranial perforation combined with a varus displacement of the neck-head
      fragment, known as "Cut Out," seen with intramedullary nails utilizing lag
      screws. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 22357091
TI  - Decisions and staging leading to definitive open management of pilon fractures: 
      where have we come from and where are we now?
AB  - Historically, the treatment and outcomes related to pilon fractures have been
      variable despite anatomical reduction and fixation. However, with the advent of
      newer implant technologies, improved surgical techniques, and the management via
      a staged protocol, results have indicated encouraging clinical outcomes with
      minimization of postoperative complications. This review focuses and outlines the
      current strategies, decision-making processes, and definitive treatment options
      regarding the notoriously difficult to treat pilon fracture. LEVEL OF EVIDENCE:
      Therapeutic Level V. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 22357092
TI  - Screw placement for acetabular fractures: which navigation modality (2
      dimensional vs. 3-dimensional) should be used? An experimental study.
AB  - OBJECTIVES: Screw navigation techniques with different image guidance [2
      dimensional (2D) vs. 3-dimensional (3D) fluoroscopy] were evaluated for
      acetabular fracture surgery. METHODS: Two-dimensional and 3D navigation images
      were analyzed for visualization of different osseous corridors: supra-acetabular,
      anterior column, posterior column, and infra-acetabular. Forty guide wires per
      group were placed in synthetic pelvis with a prefabricated soft tissue envelope
      (10 per group) using a 2D or 3D fluoroscopic navigation procedure. Duration of
      the single steps for each procedure and of cumulative fluoroscopy time was
      measured. The accuracy of guide wire placement was evaluated visually and in 3D
      cone-beam scans. RESULTS: The overall procedure time per pelvis was significantly
      reduced in the 3D group compared with the 2D group [mean +/- standard error (SE)
      (minutes): 50.11 +/- 1.38 vs. 63.42 +/- 2.32; P < 0.0001]. A trend to reduction
      in image acquisition time [mean +/- SE (minutes): 12.37 +/- 1.34 vs. 15.43 +/-
      1.03; P = not significant] and significant increase in the cumulative fluoroscopy
      time [mean +/- SE (seconds): 64 +/- 9 vs. 13 +/- 1.3; P < 0.0001) was measured in
      the 3D compared with the 2D group, caused by the 3D scan. Intra-articular
      misplacements were not observed in both the groups, but an increased accuracy
      could be achieved using the 3D image-based navigation procedure (perfect
      placement: 37 vs. 29; secure placement: 2 vs. 7; misplacement: 1 vs. 4).
      CONCLUSIONS: Both navigation procedures securely prevent an intra-articular
      penetration during drilling, but the 3D image-based navigation procedure
      increases the overall accuracy compared with the 2D image-based navigation
      technique (misplacement rates of 2.5% vs. 10%). Especially, in very narrow
      corridors (as the infra-acetabular screw path), the use of 3D navigation should
      be preferred.

PMID- 22357093
TI  - The position and number of screws influence screw perforation of the humeral head
      in modern locking plates:  a cadaver study.
AB  - OBJECTIVES: Screw perforation of the humeral head in locking plate osteosynthesis
      occurs in up to 30% of cases. The current study compared different fixation
      possibilities (eg, number and position of screws) to reduce screw perforation in
      the humeral head. METHODS: A humeral head fracture with a missing medial support
      was created in 30 fresh-frozen cadavers and fixed with a polyaxial locking plate
      (NCB PH; Zimmer, Warsaw, IN). The constructs were loaded with increasing force
      and the number of cycles until screw perforation was recorded. Four different
      fixation methods were tested: group 1 five screws with fixed angle, group 2 five
      screws in polyaxial position according to bone strength, group 3 three screws,
      and group 4 five screws with 1 as an inferomedial support screw. RESULTS: More
      screws in the humeral head significantly increased the number of cycles before
      screw perforation. An inferomedial support screw further increased the number of
      cycles. Polyaxial screw placement compared with fixed-angle placement had no
      effect on the screw perforation phenomenon. CONCLUSIONS: We recommend to position
      an inferomedial support screw, and at least 5 screws in the head fragment, when
      using a locking plate in proximal humerus fractures with disrupted medial hinge.

PMID- 22357094
TI  - The effect of movement rate and complexity on functional magnetic resonance
      signal change during pedaling.
AB  - We used functional magnetic resonance imaging (fMRI) to record human brain
      activity during slow (30 RPM), fast (60 RPM), passive (30 RPM), and variable rate
      pedaling. Ten healthy adults participated. After identifying regions of interest,
      the intensity and volume of brain activation in each region was calculated and
      compared across conditions (p < .05). Results showed that the primary sensory and
      motor cortices (S1, M1), supplementary motor area (SMA), and cerebellum (Cb) were
      active during pedaling. The intensity of activity in these areas increased with
      increasing pedaling rate and complexity. The Cb was the only brain region that
      showed significantly lower activity during passive as compared with active
      pedaling. We conclude that M1, S1, SMA, and Cb have a role in modifying
      continuous, bilateral, multijoint lower extremity movements. Much of this brain
      activity may be driven by sensory signals from the moving limbs.

PMID- 22357095
TI  - Immunohistochemical changes of nigrostriatal tyrosine hydroxylase and dopamine
      transporter in the golden hamster after a single intrastriatal injection of 6
      hydroxydopamine.
AB  - One of the most important models for analyzing the pathomorphological aspects of
      Parkinson's disease (PD) is the 6-hydroxydopamine (6-OHDA) model where lesions of
      the nigrostriatal axis are observed when 6-OHDA is intrastriatally injected.
      Despite the widespread use in rats, only few studies about the toxicity of 6-OHDA
      have been carried out in other species. In the present study, we evaluated for
      the first time the effects of a single intrastriatal injection of 6-OHDA (20 MUg
      dissolved in 2 MUl of vehicle) in the young-adult golden hamster (GH).
      Significant decreases in tyrosine hydroxylase (TH)-positive area and dopamine
      transporter (DAT)-positive area were found in the ipsilateral striatum 3 days
      after the injection. These decreases in immunoreactivity continued for 7 days and
      a recovery trend was found at days 15 and 21 post injection. On the other hand,
      no effect of injection was found on the contralateral side. In the substantia
      nigra pars compacta (SNpc), a significant decrease in the number of TH-positive
      cells appeared one week after the injection with the peak in the loss of TH
      positive immunoreactivity being recorded two weeks post-injection. On the basis
      of the results herein reported, we believe that the GH is a suitable model for
      studying the patterns of spontaneous recovery of striatal axons following the 6
      OHDA intrastriatal injection.

PMID- 22357096
TI  - Single beat 3D echocardiography for the assessment of right ventricular dimension
      and function after endurance exercise: Intraindividual comparison with magnetic
      resonance imaging.
AB  - BACKGROUND: Our study compares new single beat 3D echocardiography (sb3DE) to
      cardiovascular magnetic resonance imaging (CMR) for the measurement of right
      ventricular (RV) dimension and function immediately after a 30 km run. This is to
      validate sb3DE against the "gold standard" CMR and to bring new insights into
      acute changes of RV dimension and function after endurance exercise. METHODS: 21
      non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000,
      matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5
      Tesla) and blood tests before and immediately after each athlete ran 30 km. The
      runners were not allowed to rehydrate after the race. The order of sb3DE and CMR
      examination was randomized. RESULTS: Sb3DE for the acquisition of RV dimension
      and function was feasible in all subjects. The decrease in mean body weight and
      the significant increase in hematocrit indicated dehydration. RV dimensions
      measured by CMR were consistently larger than measured by sb3DE.Neither sb3DE nor
      CMR showed a significant difference in the RV ejection fraction before and after
      exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by
      sb3DE, this decrease of RV volumes was not significant. CONCLUSION: First, both
      methods agree well in the acquisition of systolic RV function. The dimensions of
      the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV
      volumes decrease significantly when measured by CMR compared to baseline.Second,
      endurance exercise seems not to induce acute RV dysfunction in athletes without
      rehydration.

PMID- 22357097
TI  - Incidence, risk factors, and natural course of proximal junctional kyphosis:
      surgical outcomes review of adult idiopathic scoliosis. Minimum 5 years of follow
      up.
AB  - STUDY DESIGN: A retrospective case series of surgically treated patients with
      adult scoliosis. OBJECTIVE: The purpose of this study was to evaluate the
      incidence, risk factors, and natural course of proximal junctional kyphosis (PJK)
      in a long-term follow-up of patients with adult idiopathic scoliosis undergoing
      long instrumented spinal fusion. SUMMARY OF BACKGROUND DATA: Although recent
      reports have showed the prevalence, clinical outcomes, and the possible risk
      factors of PJK, quite a few reports have showed long-term follow-up outcome.
      MATERIALS AND METHODS: This is a retrospective review of the charts and
      radiographs of 76 consecutive patients with adult scoliosis treated with long
      instrumented spinal fusion. Radiographical measurements and demographic data were
      reviewed on preoperation, immediate postoperation, 2 years postoperation, 5 years
      postoperation, and at follow-up. Postoperative Scoliosis Research Society scores
      and Oswestry Disability Index were also evaluated. Means were compared with
      Student t test. A P value of less than 0.05 with 95% confidence interval was
      considered significant. RESULTS: The mean age was 48.8 years (range, 23-75 yr)
      and the average follow-up was 7.3 years (range, 5-14 yr). PJK has been identified
      in 17 patients. The Scoliosis Research Society and Oswestry Disability Index did
      not demonstrate significant differences between PJK group and non-PJK group; 2
      patients had additional surgeries performed for local pain. Seventy-six percent
      of PJK has been identified within 3 months after surgery. Despite the fact that
      53% of total degree of PJK was progressed within 3 months after surgery, PJK
      continuously progressed to the final follow-up. Pre-existing low bone mineral
      density, posterior spinal fusion (PSF), fusion to sacrum, inappropriate global
      spine alignment, and greater sagittal vertical axis change were identified as
      significant risk factors for PJK (P = 0.04, P < 0.001, P = 0.02, P < 0.0001, and
      P = 0.01). CONCLUSION: In a long-term review of minimum 5 years, 76% of PJK
      occurred within 3 months after surgery. Pre-existing low bone mineral density,
      PSF, fusion to the sacrum, inappropriate global spine alignment, and greater
      sagittal vertical axis change were significant risk factors for PJK. Careful long
      term follow-up should be done for a patient with PJK.

PMID- 22357098
TI  - Environmental risks to public health in the United Arab Emirates: a quantitative
      assessment and strategic plan.
AB  - BACKGROUND: Environmental risks to health in the United Arab Emirates (UAE) have
      shifted rapidly from infectious to noninfectious diseases as the nation has
      developed at an unprecedented rate. In response to public concerns over newly
      emerging environmental risks, the Environment Agency-Abu Dhabi commissioned a
      multidisciplinary environmental health strategic planning project. OBJECTIVES: In
      order to develop the environmental health strategic plan, we sought to quantify
      the illnesses and premature deaths in the UAE attributable to 14 environmental
      pollutant categories, prioritize these 14 risk factors, and identify
      interventions. METHODS: We estimated the disease burden imposed by each risk
      factor using an attributable fraction approach, and we prioritized the risks
      using an empirically tested stakeholder engagement process. We then engaged
      government personnel, scientists, and other stakeholders to identify
      interventions. RESULTS: The UAE's environmental disease burden is low by global
      standards. Ambient air pollution is the leading contributor to premature
      mortality [~ 650 annual deaths; 95% confidence interval (CI): 140, 1,400]. Risk
      factors leading to > 10,000 annual health care facility visits included
      occupational exposures, indoor air pollution, drinking water contamination,
      seafood contamination, and ambient air pollution. Among the 14 risks considered,
      on average, outdoor air pollution was ranked by the stakeholders as the highest
      priority (mean rank, 1.4; interquartile range, 1-2) and indoor air pollution as
      the second-highest priority (mean rank 3.3; interquartile range, 2-4). The
      resulting strategic plan identified 216 potential interventions for reducing
      environmental risks to health. CONCLUSIONS: The strategic planning exercise
      described here provides a framework for systematically deciding how to invest
      public funds to maximize expected returns in environmental health, where returns
      are measured in terms of reductions in a population's environmental burden of
      disease.

PMID- 22357099
TI  - Regulatory properties of the intestinal microbiome effecting the development and
      treatment of diabetes.
AB  - PURPOSE OF REVIEW: The microbiome continues to demonstrate an important role in
      immune and metabolic programming. This review will focus on the mechanistic
      implications of recent findings for diabetes pathogenesis and treatment. RECENT
      FINDINGS: Multiple techniques are developing to specify the microbiome. At the
      same time, new insights have emerged into local interactions of microbial
      products with human development. New findings demonstrate that key bacteria and
      their products result in the programming of diabetes-modulating Th17 and
      regulatory T lymphocytes within and outside the intestine. The role of the
      bacterial metagenome in programming human metabolism has also revealed new
      insights. In turn, these findings suggest a framework in which the microbiome may
      be modified to change the course of diabetes. SUMMARY: The microbiome is a key
      regulator of metabolism and immunity. Specific bacteria and their secreted
      products are now known to program Th17 and regulatory T-cell development, which
      may change the course of diabetes. Bacterial genomics are demonstrating
      important, modifiable roles of bacterial gene products in metabolism. Further
      understanding of this symbiotic relationship will provide new avenues for
      intervention in diabetes.

PMID- 22357100
TI  - Prevalence of hepatitis B virus infection among blood donors at the Tamale
      Teaching Hospital, Ghana (2009).
AB  - BACKGROUND: Despite education and availability of drugs and vaccines, hepatitis B
      virus (HBV) is still the most common severe liver infection in the world
      accounting for >1 million annual deaths worldwide. Transfusion of infected blood,
      unprotected sex and mother to child transmission are 3 key transmission routes of
      HBV in Ghana. There is high incidence of blood demanding health situations in
      northern Ghana resulting from anemia, accidents, malnutrition, etc. The higher
      the demand, the higher the possibility of transmitting HBV through infected
      blood. The aim of the investigation was to estimate the prevalence of HBV in
      blood donors which will provide justification for interventions that will help
      minimize or eliminate HBV infection in Ghana. FINDINGS: We investigated the
      prevalence of HBV infection among blood donors at Tamale Teaching Hospital. The
      Wondfo HBsAg test kit was used to determine the concentration of HBsAg in 6,462
      (576 voluntary and 5,878 replacement) donors as being >=1 ng/ml. 10.79% of
      voluntary donors and 11.59% of replacement donors were HBsAg+. The 20-29 year
      group of voluntary donors was >2 times more likely to be HBsAg + than 40-60. Also
      the 20-29 year category of replacement donors was >4 times as likely to be HBsAg
      + than 50-69. CONCLUSIONS: Risk of infection was age, sex and donor type
      dependent. The 20-29 year category had the highest prevalence of HBsAg + cases,
      mostly males residing within the metropolis.

PMID- 22357102
TI  - Cytogenetic analysis of gingival epithelial cells, as related to smoking habits
      and occurrence of periodontal disease.
AB  - Periodontal disease, progressing from gingivitis to periodontitis, affects the
      majority of the world population. Its pathogenesis is related to a complex
      interaction between environmental, microbial, genetic and other host factors,
      tobacco smoking being the most important environmental risk factor. Conflicting
      results are reported in the literature regarding the effects of smoking habits on
      cytogenetic damage in exfoliated oral cells. We report herein the results of a
      study evaluating, for the first time, the frequency of micronucleated and
      binucleated cells in the gingival epithelium. There was no significant elevation
      of these cytogenetic end-points in 43 subjects as related to smoking habits
      (never-smokers, ex-smokers, and current smokers) and periodontal disease (mild,
      moderate, or severe forms of gingivitis and periodontitis). Therefore, the
      overall data emerging from the present study do not support the evidence for an
      association between smoking habits, periodontal disease and genotoxic damage in
      gingival epithelial cells.

PMID- 22357104
TI  - UN Envoy's response to estimates of global malaria mortality.

PMID- 22357103
TI  - Grip type and task goal modify reach-to-grasp performance in post-stroke
      hemiparesis.
AB  - This study investigated whether grip type and/or task goal influenced reaching
      and grasping performance in poststroke hemiparesis. Sixteen adults with
      poststroke hemiparesis and twelve healthy adults reached to and grasped a
      cylindrical object using one of two grip types (3-finger or palmar) to achieve
      one of two task goals (hold or lift). Performance of the stroke group was
      characteristic of hemiparetic limb movement during reach-to-grasp, with more
      curved handpaths and slower velocities compared with the control group. These
      effects were present regardless of grip type or task goal. Other measures of
      reaching (reach time and reach velocity at object contact) and grasping (peak
      thumb-index finger aperture during the reach and peak grip force during the
      grasp) were differentially affected by grip type, task goal, or both, despite the
      presence of hemiparesis, providing new evidence that changes in motor patterns
      after stroke may occur to compensate for stroke-related motor impairment.

PMID- 22357101
TI  - Regulation of NAD(P)H oxidases by AMPK in cardiovascular systems.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are
      ubiquitously produced in cardiovascular systems. Under physiological conditions,
      ROS/RNS function as signaling molecules that are essential in maintaining
      cardiovascular function. Aberrant concentrations of ROS/RNS have been
      demonstrated in cardiovascular diseases owing to increased production or
      decreased scavenging, which have been considered common pathways for the
      initiation and progression of cardiovascular diseases such as atherosclerosis,
      hypertension, (re)stenosis, and congestive heart failure. NAD(P)H oxidases are
      primary sources of ROS and can be induced or activated by all known
      cardiovascular risk factors. Stresses, hormones, vasoactive agents, and cytokines
      via different signaling cascades control the expression and activity of these
      enzymes and of their regulatory subunits. But the molecular mechanisms by which
      NAD(P)H oxidase is regulated in cardiovascular systems remain poorly
      characterized. Investigations by us and others suggest that adenosine
      monophosphate-activated protein kinase (AMPK), as an energy sensor and modulator,
      is highly sensitive to ROS/RNS. We have also obtained convincing evidence that
      AMPK is a physiological suppressor of NAD(P)H oxidase in multiple cardiovascular
      cell systems. In this review, we summarize our current understanding of how AMPK
      functions as a physiological repressor of NAD(P)H oxidase.

PMID- 22357105
TI  - Paediatricians oppose Health and Social Care Bill.

PMID- 22357107
TI  - Improving medication safety.

PMID- 22357106
TI  - A pharmacist-led information technology intervention for medication errors
      (PINCER): a multicentre, cluster randomised, controlled trial and cost
      effectiveness analysis.
AB  - BACKGROUND: Medication errors are common in primary care and are associated with
      considerable risk of patient harm. We tested whether a pharmacist-led,
      information technology-based intervention was more effective than simple feedback
      in reducing the number of patients at risk of measures related to hazardous
      prescribing and inadequate blood-test monitoring of medicines 6 months after the
      intervention. METHODS: In this pragmatic, cluster randomised trial general
      practices in the UK were stratified by research site and list size, and randomly
      assigned by a web-based randomisation service in block sizes of two or four to
      one of two groups. The practices were allocated to either computer-generated
      simple feedback for at-risk patients (control) or a pharmacist-led information
      technology intervention (PINCER), composed of feedback, educational outreach, and
      dedicated support. The allocation was masked to researchers and statisticians
      involved in processing and analysing the data. The allocation was not masked to
      general practices, pharmacists, patients, or researchers who visited practices to
      extract data. [corrected]. Primary outcomes were the proportions of patients at 6
      months after the intervention who had had any of three clinically important
      errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed
      to those with a history of peptic ulcer without co-prescription of a proton-pump
      inhibitor; beta blockers prescribed to those with a history of asthma; long-term
      prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics
      to those 75 years or older without assessment of urea and electrolytes in the
      preceding 15 months. The cost per error avoided was estimated by incremental cost
      effectiveness analysis. This study is registered with Controlled-Trials.com,
      number ISRCTN21785299. FINDINGS: 72 general practices with a combined list size
      of 480,942 patients were randomised. At 6 months' follow-up, patients in the
      PINCER group were significantly less likely to have been prescribed a non
      selective NSAID if they had a history of peptic ulcer without gastroprotection
      (OR 0.58, 95% CI 0.38-0.89); a beta blocker if they had asthma (0.73, 0.58-0.91);
      or an ACE inhibitor or loop diuretic without appropriate monitoring (0.51, 0.34
      0.78). PINCER has a 95% probability of being cost effective if the decision
      maker's ceiling willingness to pay reaches L75 per error avoided at 6 months.
      INTERPRETATION: The PINCER intervention is an effective method for reducing a
      range of medication errors in general practices with computerised clinical
      records. FUNDING: Patient Safety Research Portfolio, Department of Health,
      England.

PMID- 22357108
TI  - AIDA STEMI: no benefit for intracoronary abciximab.

PMID- 22357109
TI  - Intracoronary versus intravenous bolus abciximab during primary percutaneous
      coronary intervention in patients with acute ST-elevation myocardial infarction:
      a randomised trial.
AB  - BACKGROUND: Intracoronary administration of an abciximab bolus during a primary
      percutaneous coronary intervention results in a high local drug concentration,
      improved perfusion, and reduction of infarct size compared with intravenous bolus
      application. However, the safety and efficacy of intracoronary versus standard
      intravenous bolus application in patients with ST-elevation myocardial infarction
      (STEMI) undergoing this intervention has not been tested in a large-scale
      clinical trial. METHODS: The AIDA STEMI trial was a randomised, open-label,
      multicentre trial. Patients presenting with STEMI in the previous 12 h with no
      contraindications for abciximab were randomly assigned in a 1:1 ratio by a
      central web-based randomisation system to intracoronary versus intravenous
      abciximab bolus (0.25 mg/kg bodyweight) during percutaneous coronary intervention
      with a subsequent 12 h intravenous infusion 0.125 MUg/kg per min (maximum 10
      MUg/min). The primary endpoint was a composite of all-cause mortality, recurrent
      infarction, or new congestive heart failure within 90 days of randomisation.
      Secondary endpoints were the time to occurrence of the primary endpoint, each
      individual component of that endpoint, early ST-segment resolution, thrombolysis
      in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked
      central committee adjudicated the primary outcome and its components. Treatment
      allocation was not concealed from patients and investigators. This trial is
      registered with ClinicalTrials.gov, NCT00712101. FINDINGS: Between July, 2008,
      and April, 2011, 2065 patients were randomly assigned intracoronary abciximab
      (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with
      intravenous abciximab, resulted in a similar rate of the primary composite
      clinical endpoint at 90 days in 1876 analysable patients (7.0%vs 7.6%; odds ratio
      [OR] 0.91; 95% CI 0.64-1.28; p=0.58). The incidence of death (4.5%vs 3.6%; 1.24;
      0.78-1.97; p=0.36) and reinfarction (1.8%vs 1.8%; 1.0; 0.51-1.96; p=0.99) did not
      differ between the treatment groups, whereas less patients in the intracoronary
      group had new congestive heart failure (2.4%vs 4.1%; 0.57; 0.33-0.97; p=0.04).
      None of the secondary endpoints or safety measures differed significantly between
      groups. INTERPRETATION: In patients with STEMI undergoing primary percutaneous
      coronary intervention, intracoronary as compared to intravenous abciximab did not
      result in a difference in the combined endpoint of death, reinfarction, or
      congestive heart failure. Since intracoronary abciximab bolus administration is
      safe and might be related to reduced rates of congestive heart failure the
      intracoronary route might be preferred if abciximab is indicated. FUNDING: Lilly,
      Germany. University of Leipzig-Heart Centre. University of Leipzig, Clinical
      Trial Centre Leipzig, supported by the Federal Ministry of Education and Research
      (BMBF).

PMID- 22357111
TI  - Viral infections in patients with inflammatory bowel disease on
      immunosuppressants.
AB  - The use of immunosuppressant medications and biologics such as tumor necrosis
      factor alpha antagonists has revolutionized the treatment of inflammatory bowel
      disease. With increasing use of such agents, the risk of serious infections is a
      key safety concern for treated patients. Greater physician awareness about these
      potential infections is important to optimize patient outcomes through early
      recognition and potential preventive strategies. The authors present a
      comprehensive and concise review of clinically important viral infections
      associated with the inflammatory bowel disease therapy.

PMID- 22357112
TI  - Design, synthesis and evaluation of telomerase inhibitory, hTERT repressing, and
      anti-proliferation activities of symmetrical 1,8-disubstituted
      amidoanthraquinones.
AB  - A series of symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized
      and evaluated for anti-proliferation, telomerase inhibitory by TRAP assay, and
      hTERT expression by SEAP assay. All of the compounds tested, except for compounds
      3a and 3s were selected by the NCI screening system. In addition, compounds 4e
      and 4k exhibited inhibitory effects on telomerase activity. Taken together, our
      findings indicated that the analysis of cytotoxicity and telomerase inhibition
      might provide information applicable for further developing potential telomerase
      targeting strategy.

PMID- 22357113
TI  - Design, synthesis, computational and biological evaluation of some new hydrazino
      derivatives of DHA and pyranopyrazoles.
AB  - Two series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H
      pyran-2-ones (4a-4j) and pyrano[4,3-c]pyrazoles (6a-6e and 6g) were synthesized
      starting from 3-acetyl-4-chloro-6-methyl-2H-pyran-2-one (2). Estimation of
      pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side
      effects and interaction with drug-metabolizing enzymes were made for the
      synthesized compounds on the basis of prediction of activity spectra for
      substances (PASS) prediction results and their analysis by PharmaExpert software.
      COX inhibition predicted by PASS was confirmed by experimental evaluation and
      validated via docking studies. Out of all the compounds, compounds 4h, 4j, 6e, 6g
      exhibited good anti-inflammatory activity, whereas compounds 4b, 4c, 4h, 4i, 4j,
      6b, 6e, 6g showed excellent analgesic activity compared with standard drug
      Diclofenac sodium.

PMID- 22357114
TI  - Influence of susceptibility to hydrolysis and hydrophobicity of
      arylsemicarbazones on their anti-nociceptive and anti-inflammatory activities.
AB  - Benzaldehyde semicarbazone (BS) inhibited zymosan writhing response, carrageenan
      paw edema and both phases of formaldehyde nociceptive response. 2
      hydroxybenzaldehyde semicarbazone (2-OHBS) and semicarbazide inhibited
      carrageenan paw edema and the second phase of formaldehyde nociceptive response.
      2-OHBS inhibited zymosan writhing response. 3- and 4-OHBS did not show such
      activities. 2-OHBS showed the lowest LUMO energy, the highest contribution of the
      iminic carbon to LUMO energy, the highest positive charge on the iminic carbon,
      the highest negative charge on the iminic nitrogen and the highest susceptibility
      to hydrolysis. Hence semicarbazide may play important roles in 2-OHBS's
      activities. Inhibition of the first phase of formaldehyde response by BS could be
      attributed to its higher hydrophobicity and lower susceptibility to hydrolysis in
      comparison to 2-OHBS.

PMID- 22357115
TI  - 2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III)
      complexes are highly cytotoxic to glioma cells.
AB  - 2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone
      (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO(2)Ph) analogues, the
      corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and
      H2BzpNO(2)Ph) and their gallium(III) complexes were assayed for their cytotoxic
      activity against U87 (expressing wild-type p53 protein) and T98 (expressing
      mutant p53 protein) glioma cells. IC(50) values against both glioma cells and
      against the MRC5 (human fetal lung fibroblast) lineage were obtained for the
      hydrazones, but not for their gallium(III) complexes, due to their low
      solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and
      T98 cells. The therapeutic indexes (TI = IC(50MRC5)/IC(50glioma)) were 2-660 for
      T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could
      be good antitumor drug candidates to treat brain tumors.

PMID- 22357116
TI  - Evidence base for probiotic products for the pediatric population.

PMID- 22357118
TI  - Inflammatory bowel disease manifesting after surgical treatment for Hirschsprung
      disease.
AB  - Eight children developed chronic inflammatory bowel disease (IBD) 4 to 21 years
      after surgery for Hirschsprung disease. Three had trisomy 21 and 6 experienced
      chronic or recurrent enterocolitis. Four had a family history of IBD. Clinical
      presentation included chronic diarrhea, hematochezia, abscess, and fistula
      formation. Three required surgery for fistula, stricture, and small bowel
      obstruction and the other 5 were managed medically. Recognition of this condition
      may be important in the long-term follow-up of children with Hirschsprung
      disease, and patients who have carried a diagnosis of chronic enterocolitis may
      warrant further investigation looking for evidence of IBD.

PMID- 22357117
TI  - Definitions of pediatric pancreatitis and survey of present clinical practices.
AB  - OBJECTIVES: There is limited literature on acute pancreatitis (AP), acute
      recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The
      International Study Group of Pediatric Pancreatitis: In Search for a Cure
      (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic
      algorithms, investigate disease pathophysiology, and design prospective
      multicenter studies in pediatric pancreatitis. METHODS: Subcommittees were formed
      to delineate definitions of pancreatitis, and a survey was conducted to analyze
      present practice. RESULTS: AP was defined as requiring 2 of the following:
      abdominal pain compatible with AP, serum amylase and/or lipase values >=3 times
      upper limits of normal, and imaging findings of AP. ARP was defined as >=2
      distinct episodes of AP with intervening return to baseline. CP was diagnosed in
      the presence of typical abdominal pain plus characteristic imaging findings, or
      exocrine insufficiency plus imaging findings, or endocrine insufficiency plus
      imaging findings. We found that children with pancreatitis were primarily managed
      by pediatric gastroenterologists. Unless the etiology was known, initial
      investigations included serum liver enzymes, triglycerides, calcium, and
      abdominal ultrasound. Further investigations (usually for ARP and CP) included
      magnetic resonance or other imaging, sweat chloride, and genetic testing.
      Respondents' future goals for INSPPIRE included determining natural history of
      pancreatitis, developing algorithms to evaluate and manage pancreatitis, and
      validating diagnostic criteria. CONCLUSIONS: INSPPIRE represents the first
      initiative to create a multicenter approach to systematically characterize
      pancreatitis in children. Future aims include creation of patient database and
      biologic sample repository.

PMID- 22357119
TI  - Effects of freezing on the bactericidal activity of human milk.
AB  - OBJECTIVES: Storage of human milk by freezing has been recommended for long-term
      storage. The present study analyzed the bactericidal activity of human milk on
      Escherichia coli and Pseudomonas aeruginosa and determined the changes in
      bactericidal activity following freezing at -20 degrees C and -80 degrees C for 1
      month and 3 months. METHODS: Forty-eight milk samples were collected from 48
      lactating mothers. Each sample was divided into 10 aliquots. Two of the samples
      were processed immediately and the others were stored at both -20 degrees C and 
      80 degrees C until analysis after 1 month and 3 months of freezing. RESULTS: All
      of the fresh milk samples showed bactericidal activity against E coli and P
      aeruginosa. Freezing at -20 degrees C for 1 month did not cause statistically
      significant alteration in bactericidal activity (P > 0.017), whereas storage for
      3 months lowered the degree of bactericidal activity significantly (P < 0.017)
      against E coli. Bactericidal activity was protected when the samples were stored
      at -80 degrees C. There was no statistically significant difference in the
      bactericidal activity of human milk against E coli between freezing at -20
      degrees C and -80 degrees C for 1 month (P > 0.017); however, when milk was
      stored for 3 months, -80 degrees C was significantly more protective (P < 0.017).
      Freezing at -20 degrees C and -80 degrees C for 1 month and 3 months did not
      cause any significant change in bactericidal activity against P aeruginosa (P >
      0.05). CONCLUSIONS: Storage by freezing at -80 degrees C is more appropriate to
      keep bactericidal capacity of stored human milk >1 month if affordable and
      available, especially in intensive care settings.

PMID- 22357120
TI  - Incidence of peptic ulcer bleeding in the US pediatric population.
AB  - OBJECTIVES: The aim of the present study was to determine the incidence of peptic
      ulcer bleeding (PUB) in pediatric patients. METHODS: A hospital inpatient
      database, Premier Perspective, and an insurance claims database, MarketScan, were
      analyzed to estimate upper and lower limits for the annual incidence of PUB in
      the US pediatric population. RESULTS: Using data from the Premier Perspective
      database and database-specific projection methodology, the total number of cases
      of hospitalization of pediatric patients for PUB in the United States in 2008 was
      estimated to be between 378 and 652. This translated to an incidence of 0.5 to
      0.9/100,000 individuals in the pediatric population. Using data from the
      MarketScan database, the incidence of PUB in the insured pediatric population was
      estimated to be 4.4/100,000 individuals. Overall, 17.4% of insured pediatric
      patients diagnosed as having any upper gastrointestinal ulcer in 2008 were
      reported to have developed PUB. CONCLUSIONS: The estimated incidence of PUB in
      the US pediatric population in 2008 ranged from 0.5 to 4.4/100,000 individuals.
      The total number of cases of PUB in pediatric patients in the United States each
      year was thus estimated to be between 378 and 3250. Such estimates provide a
      likely lower and upper limit for the total number of cases of the condition
      annually.

PMID- 22357121
TI  - Arterioesophageal fistula after stenting for esophageal atresia.

PMID- 22357122
TI  - Duodenal hamartoma:  a rare cause of gastric outlet obstruction in children.

PMID- 22357123
TI  - Diagnosing a common rater halo effect using the polytomous Rasch model.
AB  - The 'halo effect' may be unique to different raters or common to all raters. When
      common to all raters, halo is not detectable through standard fit indices of the
      three-facet Rasch model used to account for differences in rater severities.
      Using a formulation of halo as a violation of local independence, a halo effect
      common to all raters is simulated and shown to be diagnosable through contrasts
      between two-facet stack and rack Rasch analyses. In the former, the thresholds
      are clustered and the distribution of persons is multimodal; in the latter, all
      thresholds are close together and the distribution of persons is unimodal. In the
      former, the scale is stretched, and the person separation inflated, relative to
      the latter.

PMID- 22357124
TI  - A comparison of structural equation and multidimensional Rasch modeling
      approaches to Confirmatory Factor Analysis.
AB  - This paper compares the results of applications of the Multidimensional Random
      Coefficients Multinomial Logit Model (MRCMLM) to comparable Structural Equation
      Model (SEM) applications for the purpose of conducting a Confirmatory Factor
      Analysis (CFA). We review SEM as it is applied to CFA, identify some parallels
      between the MRCMLM approach to CFA and that utilized in a standard SEM CFA, and
      illustrate the comparability of MRCMLM and SEM CFA results for three datasets.
      Results indicate that the two approaches tend to identify similar dimensional
      models as exhibiting best fit and provide comparable depictions of latent
      variable correlations, but the two procedures depict the reliability of measures
      differently.

PMID- 22357125
TI  - The Rainbow Families Scale (RFS): a measure of experiences among individuals with
      lesbian and gay parents.
AB  - According to two decades of research, parental sexual orientation does not affect
      overall child development. Researchers have not found significant differences
      between offspring of heterosexual parents and those of lesbian and gay parents in
      terms of their cognitive, psychological, or emotional adjustment. Still, there
      are gaps in the literature regarding social experiences specific to offspring of
      lesbian and gay parents. This study's objective was to construct a measure of
      those experiences. The Rainbow Families Scale (RFS) was created on the basis of
      focus group discussions (N = 9 participants), and then piloted (N = 24) and
      retested with a new sample (N = 91) to examine its psychometric properties.
      Exploratory factor analyses uncovered secondary dimensions and Rasch analytic
      procedures examined item fit, reliability, and category usage. Misfitting items
      were eliminated where necessary, yielding a psychometrically sound measurement
      tool to aid in the study of individuals with lesbian and gay parents.

PMID- 22357126
TI  - Development of an instrument for measuring  self-efficacy in cell biology.
AB  - This article describes the development of a ten-item scale to assess biology
      majors' self-efficacy towards the critical thinking and data analysis skills
      taught in an upper-division cell biology course. The original seven-item scale
      was expanded to include three additional items based on the results of item
      analysis. Evidence of reliability and validity was collected and reported for the
      revised scale. In addition, the effect of varying the number of response
      categories presented with the items was empirically examined by administering
      different versions of the instrument containing 6, 11, 21, and 101 response
      categories to randomly selected samples of students in the course. Rasch scaling
      procedures were used to analyze the results. Contrary to Bandura's recommendation
      for using the 101-point scale (0-100), the results indicated that most
      respondents used only a subset of the options in the 101-point scale and that the
      6-point and 11-point scales produced less threshold disordering for the purpose
      of assessing changes in students' self-efficacy in the context of a one-semester
      course.

PMID- 22357127
TI  - Measuring schools' efforts to partner with parents of children served under IDEA:
      scaling and standard setting for accountability reporting.
AB  - Indicator 8 of the State Performance Plan (SPP), developed under the 2004
      reauthorization of the Individuals with Disabilities Education Act (IDEA 2004,
      Public Law 108-446) requires states to collect data and report findings related
      to schools' facilitation of parent involvement. The Schools' Efforts to Partner
      with Parents Scale (SEPPS) was developed to provide states with a means to
      address this new reporting requirement. Items suggested by stakeholder groups
      were piloted with a nationally representative sample of 2,634 parents of students
      with disabilities ages 5-21 in six states. Rasch scaling was used to calibrate a
      meaningful and invariant item hierarchy. The 78 calibrated items had measurement
      reliabilities ranging from .94-.97. Using data from the pilot study, stakeholders
      established a recommended performance standard set at a meaningful point in the
      item hierarchy. Implications of the findings are discussed in relation to the
      need for rigorous metrics within state accountability systems.

PMID- 22357128
TI  - An ADL measure for spinal cord injury.
AB  - Occupational therapists do not have a comprehensive, objective method for
      measuring how persons with tetraplegia perform activities of daily living (ADL)
      in their homes and communities, because SCI ADL performance is usually determined
      in rehabilitation. The ADL Habits Survey (ADLHS) is designed specifically to
      address this knowledge gap by surveying performance on relevant and meaningful
      activities in homes and communities. After a comprehensive task analysis and
      pilot development, 30 activities were selected that emphasize a broad range of
      hand and wrist, reaching, and grasping movements in compound activities. A sample
      of 49 persons with cervical spinal cord injuries responded to items. The sample
      was predominantly male, median age was 41 years, and ASIA motor classification
      levels ranged from C2 through C8/T1 with majority concentration in C4, C5, or C6
      (68%). Each participant report was rated by an occupational therapist using a
      seven category rating scale, and the item by participant response matrix (30 X
      49) was analyzed with a Rasch model for rating scales. Results showed excellent
      participant separation (>4) and very high reliability (>.95), and both item and
      participant fit values were adequate (STANDARDIZED INFIT less than absolute value
      of 3). With only two exceptions, all participants fit the Rasch rating scale
      model, and only one item "Light housekeeping" presented significant fit issues.
      Principal Components Analysis an analysis of item residuals did not reveal
      serious threats to unidimensionality. A between group fit comparison of
      participants with more versus less movement found invariant item calibrations,
      and ANOVA of participant measures found statistically significant differences
      across ASIA motor classification levels. These ADLHS results offer occupational
      therapists a new method for measuring ADL that is potentially more sensitive to
      functional changes in tetraplegia than most instruments in common use.
      Accommodation of step disorder with a three category rating scale did not
      diminish measurement properties.

PMID- 22357129
TI  - Selecting cut scores with a composite of item types: the construct mapping
      procedure.
AB  - In this paper, we describe a new method we have developed for setting cut scores
      between levels of a test. We outline the wide variety of potential methods that
      have been used for such a process, and emphasize the need for a coherent
      conceptual framework under which the variety of methods could be understood. We
      then describe our particular method, based on an item response modeling
      framework, which uses the Wright Map, a graphical model of item and threshold
      difficulties, and a piece of computer software that provides probabilities of
      various responses for scores under consideration as cut scores. Finally, we
      describe a study we conducted for the Golden State Examination in Chemistry, in
      which we investigate the classification agreement for two groups using the
      method, and also investigate the reactions of the committee members to the
      procedure and the software, and the lessons we learned from this process.

PMID- 22357130
TI  - Real-life effectiveness of extrafine beclometasone dipropionate/formoterol in
      adults with persistent asthma according to smoking status.
AB  - BACKGROUND: The efficacy and safety of extrafine beclomethasone dipropionate 100
      MUg/formoterol 6 MUg (BDP/F HFA) pressurized metered dose inhaler (pMDI) in
      patients with moderate-to-severe persistent asthma, has been demonstrated in
      randomised controlled trials (RCTs). The aim of this prospective observational
      study was to assess real-life effectiveness in terms of asthma control in smoking
      (most of the time excluded from RCTs) and non-smoking asthmatics. METHODS: Adult
      patients with persistent asthma, in whom treatment with an inhaled
      corticosteroid/long-acting beta(2)-agonist (ICS/LABA) combination is indicated,
      were included. Pulmonary function (FEV1%pred or PEF absolute value), Asthma
      Control Questionnaire (ACQ) and asthma control according to GINA criteria were
      measured at baseline as well as 2-8 months and >8-14 months after treatment
      initiation with BDP/F HFA. RESULTS: Overall, 619 patients were enrolled by 97
      investigators. In the effectiveness cohort (N = 568), at baseline, smoking
      asthmatics (N = 123) had higher ACQ6 (p < 0.0001) and lower asthma control (p =
      0.021) than non-smoking asthmatics. Treatment with BDP/F HFA pMDI was associated
      with significant (p < 0.0001) improvements in pulmonary function (+7.1% in FEV1%
      pred), ACQ6 (-1.32) and GINA asthma control (improvement of control in 49.8% of
      patients). Importantly, the same treatment benefits were observed in former or
      current smokers compared with non-smoking asthmatics. There was a reduction in
      the dose of ICS from 489 +/- 192 MUg BDP extrafine equivalents at baseline to 265
      +/- 125 MUg after one year. The drug was well-tolerated. CONCLUSION: This
      prospective cohort study demonstrates the real-life effectiveness and safety of
      BDP/F HFA in adult asthma patients, including smokers, in normal clinical
      practice.

PMID- 22357131
TI  - Apoptosis inhibition or inflammation: the role of NAIP protein expression in
      Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node.
AB  - BACKGROUND: Inhibitors of Apoptosis (IAP) family play a critical role in
      apoptosis and inflammatory response. Neuronal Apoptosis Inhibitory Protein
      (NAIP), as a member of both IAPs and NLR families (NOD-Like Receptor), is a
      unique IAP harboring NOD (Nucleotide Oligomerization Domain) and LLR (Leucine
      Rich Repeat) motifs. Considering these motifs in NAIP, it has been suggested that
      the main function of NAIP is distinct from other members of IAPs. As a member of
      NLR, NAIP mediates the assembly of 'Inflammasome' for inflammatory caspase
      activation. Pathologic expression of NAIP has been reported not only in some
      infectious and inflammatory diseases but also in some malignancies. However,
      there is no report to elucidate NAIP expression in lymphomatic malignancies.
      METHODS: In this study, we examined NAIP protein expression in 101 Formalin-Fixed
      Paraffin-Embedded blocks including samples from 39 Hodgkin Lymphoma and 23 Non
      Hodgkin Lymphoma cases in comparison with 39 control samples (30 normal and 9
      Reactive Lymphoid Hyperplasia (RLH) lymph nodes) using semi-quantitative immuno
      flourecent Staining. RESULTS: NAIP expression was not statistically different in
      lymphoma samples neither in HL nor in NHL cases comparing to normal samples.
      However, we evaluated NAIP expression in normal and RLH lymph nodes.
      Surprisingly, we have found a statistically significant-difference between the
      NAIP expression in RLH (M.R of NAIP/GAPDH expression = 0.6365 +/- 0.017) and
      normal lymph node samples (M.R of NAIP/GAPDH expression = 0.5882 +/- 0.047) (P <
      0.01). CONCLUSIONS: These findings show that the regulation of apoptosis could
      not be the main function of NAIP in the cell, so the pathologic expression of
      NAIP is not involved in lymphoma. But, we concluded that the over expression of
      NAIP has more effective role in the inflammatory response. Also, this study
      clarifies the NAIP expression level in lymphoma which is required for IAPs
      profiling in order to be used in potential translational applications of IAPs.

PMID- 22357132
TI  - Accelerating large-scale protein structure alignments with graphics processing
      units.
AB  - BACKGROUND: Large-scale protein structure alignment, an indispensable tool to
      structural bioinformatics, poses a tremendous challenge on computational
      resources. To ensure structure alignment accuracy and efficiency, efforts have
      been made to parallelize traditional alignment algorithms in grid environments.
      However, these solutions are costly and of limited accessibility. Others trade
      alignment quality for speedup by using high-level characteristics of structure
      fragments for structure comparisons. FINDINGS: We present ppsAlign, a parallel
      protein structure Alignment framework designed and optimized to exploit the
      parallelism of Graphics Processing Units (GPUs). As a general-purpose GPU
      platform, ppsAlign could take many concurrent methods, such as TM-align and Fr-TM
      align, into the parallelized algorithm design. We evaluated ppsAlign on an NVIDIA
      Tesla C2050 GPU card, and compared it with existing software solutions running on
      an AMD dual-core CPU. We observed a 36-fold speedup over TM-align, a 65-fold
      speedup over Fr-TM-align, and a 40-fold speedup over MAMMOTH. CONCLUSIONS:
      ppsAlign is a high-performance protein structure alignment tool designed to
      tackle the computational complexity issues from protein structural data. The
      solution presented in this paper allows large-scale structure comparisons to be
      performed using massive parallel computing power of GPU.

PMID- 22357133
TI  - Maximal strength training enhances strength and functional performance in chronic
      stroke survivors.
AB  - OBJECTIVE: This study aimed to demonstrate that maximal strength training
      improves muscle strength and to assess the effect of training on function,
      aerobic status, and quality-of-life among chronic stroke survivors. DESIGN: Ten
      patients acted as their own controls for 4 wks, before an 8-week training
      intervention. Patients trained 3 days/wk, with four sets of four repetitions at
      85%-95% one repetition maximum in unilateral leg press and plantarflexion with an
      emphasis on maximal mobilization of force in the concentric phase. RESULTS: After
      training, leg press strength improved by 30.6 kg (75%) and 17.8 kg (86%);
      plantarflexion strength improved by 35.5 kg (89%) and 28.5 kg (223%) for the
      unaffected and affected limbs, respectively, significantly different from the
      control period (all P < 0.01). The 6-min walk test improved by 13.9 m (within
      training period; P = 0.01), and the Timed Up and Go test time improved by 0.6
      secs (within training period; P < 0.05). There were no significant changes in
      walking economy, peak aerobic capacity, Four-Square Step Test, or health-related
      quality-of-life after training. CONCLUSIONS: Maximal strength training improved
      muscle strength in the most affected as well as in the nonaffected leg and
      improved Timed-Up-And-Go time and 6-min walk distance but did not alter Four-Step
      Square Test time, aerobic status, or quality-of-life among chronic stroke
      survivors.

PMID- 22357134
TI  - Mcl-1 regulates the survival of adult neural precursor cells.
AB  - Since the discovery of neural precursor cells (NPCs) in the adult mammalian
      brain, there has been a lot of excitement surrounding the potential for
      regeneration in the adult brain. For instance, many studies have shown that a
      significant number of NPCs will migrate to a site of injury and differentiate
      into all of the neural lineages. However, one of the main challenges affecting
      endogenous neural regeneration is that many of the NPCs that migrate to the
      injury site ultimately undergo apoptosis. Therefore, we sought to determine
      whether myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 protein, would
      promote the survival of adult NPCs by impeding apoptosis. To do this, we first
      confirmed that Mcl-1 is endogenously expressed within the adult NPC population
      using BrdU labeling assays. Next, we conditionally deleted Mcl-1 in adult NPCs
      using cre/lox technology and expressed Cre from the NPC-specific promoter Nestin.
      In vitro, cells that had Mcl-1 conditionally deleted had a 2-fold increase in
      apoptosis when compared to controls. In vivo, we used electroporation to
      conditionally delete Mcl-1 in adult NPCs and assessed apoptosis at 72h. after
      electroporation. As in our in vitro results, there was a 2-fold increase in
      apoptosis when Mcl-1 was conditionally deleted. Finally, we found that Mcl-1 over
      expression reduced the endogenous rate of adult NPC apoptosis 2-fold in vitro.
      Collectively, these results demonstrate that Mcl-1 is crucial for the survival of
      adult NPCs and may be a promising target for future neural regeneration
      therapies.

PMID- 22357135
TI  - Current world literature.

PMID- 22357136
TI  - Enteral feeding:  Retraction.

PMID- 22357138
TI  - Indoor air pollutants and health in the United Arab Emirates.
AB  - BACKGROUND: Comprehensive global data on the health effects of indoor air
      pollutants are lacking. There are few large population-based multi-air pollutant
      health assessments. Further, little is known about indoor air health risks in the
      Middle East, especially in countries undergoing rapid economic development.
      OBJECTIVES: To provide multifactorial indoor air exposure and health data, we
      conducted a population-based study of indoor air pollution and health in the
      United Arab Emirates (UAE). METHODS: We conducted a cross-sectional study in a
      population-based sample of 628 households in the UAE. Indoor air pollutants
      [sulfur dioxide (SO2), nitrogen dioxide (NO2), hydrogen sulfide (H2S),
      formaldehyde (HCHO), carbon monoxide (CO), and particulate matter] were measured
      using passive samplers over a 7-day period. Health information was collected from
      1,590 household members via in-person interviews. RESULTS: Participants in
      households with quantified SO2, NO2, and H2S (i.e., with measured concentrations
      above the limit of quantification) were twice as likely to report doctor
      diagnosed asthma. Participants in homes with quantified SO2 were more likely to
      report wheezing symptoms {ever wheezing, prevalence odds ratio [POR] 1.79 [95%
      confidence interval (CI) 1.05, 3.05]; speech-limiting wheeze, POR 3.53 (95% CI:
      1.06, 11.74)}. NO2 and H2S were similarly associated with wheezing symptoms.
      Quantified HCHO was associated with neurologic symptoms (difficulty concentrating
      POR 1.47; 95% CI: 1.02, 2.13). Burning incense daily was associated with
      increased headaches (POR 1.87; 95% CI: 1.09, 3.21), difficulty concentrating (POR
      3.08; 95% CI: 1.70, 5.58), and forgetfulness (POR 2.68: 95% CI: 1.47, 4.89).
      CONCLUSIONS: This study provides new information regarding potential health risks
      from pollutants commonly found in indoor environments in the UAE and other
      countries. Multipollutant exposure and health assessments in cohort studies are
      needed to better characterize health effects of indoor air pollutants.

PMID- 22357139
TI  - Anti-CD22 therapy in acute lymphoblastic leukaemia.

PMID- 22357141
TI  - Tools for genome-wide strain design and construction.
AB  - Advances in DNA sequencing and synthesis technologies concurrent with the
      development of new recombinant DNA approaches have enabled the extension of
      directed evolution algorithms to the genome-scale. It is now possible to
      simultaneously map the effect of mutation(s) in each and every gene in the genome
      onto almost any screenable or selectable phenotype in less than a week. Such maps
      can be used to direct the design and construction of libraries containing
      billions of rationally designed combinatorial mutations. Such combinatorial
      libraries can now also be created and evaluated in less than a week. The review
      presents and discusses these new technologies within the context of directed
      evolution and inverse metabolic engineering.

PMID- 22357140
TI  - Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and
      relapsed acute lymphocytic leukaemia: a phase 2 study.
AB  - BACKGROUND: The outlook for patients with refractory and relapsed acute
      lymphocytic leukaemia (ALL) is poor. CD22 is highly expressed in patients with
      ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin
      calecheamicin. We did a phase 2 study to assess the efficacy of this antibody.
      METHODS: We recruited patients at the MD Anderson Cancer Center, Houston, TX,
      USA, between June, 2010, and March, 2011. Adults and children with refractory and
      relapsed ALL were eligible. Ten adults were treated before enrolment of children
      started. Patients were given 1.8 mg/m(2) inotuzumab ozogamicin intravenously over
      1 h every 3-4 weeks (the first three adults and three children received 1.3
      mg/m(2) in the first course). The primary endpoint was overall response (complete
      response or marrow complete response with no recovery of platelet count or
      incomplete recovery of neutrophil and platelet counts). Analysis was done by
      intention to treat. This study is registered, number NCT01134575. FINDINGS: 49
      patients were enrolled and treated. Median age was 36 years (range 6-80). CD22
      was expressed in more than 50% of blasts in all patients. The median number of
      courses was two (range one to five) and the median time between courses was 3
      weeks (range 3-6). Nine (18%) patients had complete response, 19 (39%) had marrow
      complete response, 19 (39%) had resistant disease, and two (4%) died within 4
      weeks of starting treatment. The overall response rate was 57% (95% CI 42-71).
      The most frequent adverse events during course one of treatment were fever (grade
      1-2 in 20 patients, grade 3-4 in nine), hypotension (grade 1-2 in 12 patients,
      grade 3 in one), and liver-related toxic effects (bilirubin: grade 1-2 in 12
      patients, grade 3 in two; raised aminotransferase concentration: grade 1-2 in 27
      patients, grade 3 in one). INTERPRETATION: Inotuzumab ozogamicin shows promise as
      a treatment for refractory and relapsed ALL. FUNDING: Pfizer.

PMID- 22357142
TI  - MECC regional initiative in pediatric palliative care: Middle Eastern course on
      pain management.
AB  - In all the major medical centers throughout the Middle East, there is a
      functioning pediatric hematology oncology department. In almost all countries,
      opioids such as morphine, oxycodone, and fentanyl are available. Pediatric
      palliative care services are still in their infancy and await further recognition
      and development. Unfortunately, there are still countries in the Middle East
      where children with cancer are diagnosed when the disease is already at stage III
      or IV, when the only option left is palliation. To decrease the incidence of late
      presentation, more effort is needed concerning public awareness, and
      concomitantly, an urgent need to develop hospital-based and community-based
      palliative and supportive care services. The initial step in this direction would
      involve more training of health care providers: Pediatricians, Pediatric
      Oncologists, Oncology Nurses, and Social Workers with updated pharmacological and
      nonpharmacological modalities of treatment.

PMID- 22357143
TI  - Pediatric oncology in Turkey.
AB  - The survival of children with cancer has increased dramatically in the last
      decades, as a result of advances in diagnosis, treatment and supportive care.
      Each year in Turkey, 2500-3000 new childhood cancer cases are expected. According
      to the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology
      Societies Registry, about 2000 new pediatric cancer cases are reported each year.
      The population in Turkey is relatively young. One fourth of the population is
      younger than 15 years of age. According to childhood mortality, cancer is the
      fourth cause of death (7.2%) after infections, cardiac deaths and accidents. The
      major cancers in children in Turkey are leukemia (31%), lymphoma (19%), central
      nervous system (CNS) neoplasms (13%), neuroblastomas (7%), bone tumors (6.1%),
      soft tissue sarcomas (6%), followed by renal tumors, germ cell tumors,
      retinoblastoma, carcinomas-epithelial neoplasms, hepatic tumors and others.
      Lymphomas rank second in frequency as in many developing countries in contrast to
      West Europe or USA, where CNS neoplasms rank second in frequency. The seven-year
      survival rate in children with malignancies in Turkey is 65.8%. The history of
      modern Pediatric Oncology in Turkey dates back to the 1970's. Pediatric Oncology
      has been accepted as a subspecialty in Turkey since 1983. Pediatric Oncologists
      are all well trained and dedicated. All costs for the diagnosis and treatment of
      children with cancer is covered by the government. Education and infrastructure
      for palliative care needs improvement.

PMID- 22357144
TI  - Pediatric oncology situation analysis (Jordan).
AB  - This article highlights the current situation of pediatric oncology in Jordan by
      reviewing the available population based data from the surveillance. Cancer among
      children aged less than 15 years make up 4 to 6% of all registered new cancer
      cases in all ages each year. The major types of cancer in females for the year
      2008 are leukemia 32.2%, central nervous system 18.8%, skeletal and soft tissue
      8.8%, lymphomas 5.5%, and sympathetic 5.5%, whereas in males, they are leukemia
      28.1%, central nervous system 18.8%, lymphomas 16.2%, skeletal and soft tissue 7%
      and sympathetic 6.3%. Children with cancer receive treatment through pediatric
      oncology wards in King Hussein Cancer Center (KHCC) and Royal Medical Services
      hospital or through pediatric departments in King Abdullah university Hospital
      and Princes Rahma hospital with full government coverage of the treatment
      expenses. Currently the pediatric palliative care program is limited to KHCC
      which provides inpatient care, and out-patients and drop-in care on a daily basis
      to provide symptom management, counseling, and other services as appropriate. The
      lack of palliative care in other hospital and pediatric home care coverage stress
      the need to develop special plan of action to initiate these services.

PMID- 22357145
TI  - Future planning to upgrade the pediatric oncology service in the Baghdad children
      welfare teaching hospital.
AB  - In Iraq; the community has suffered considerably in the past 40 years that makes
      any attempt of repair very difficult. Our hospital operates below the standard on
      all levels, the pediatric oncology unit, which has a capacity of 30 single beds,
      is occupied by double or triples. In 2010; new patients with cancer reached 366.
      Drug shortages, limitation of diagnostic facilities, lack of infection control
      and pain management have major impact on the management of children with cancer.
      Telemedicine program has an impact to improve the service; we have just ourselves
      and feelings of responsibility to keep motivation and looking forward for any
      help to continue.

PMID- 22357146
TI  - Pediatric oncology in Morocco: achievements and challenges.
AB  - Cancer in children is quickly becoming one of the leading causes of non traumatic
      death among children. In pediatric oncology, palliative care is a primary
      component of the cancer control plan. In low income countries also known as
      emerging nations or developing countries access to adequate care remains a
      challenge for most pediatric oncology patients. In Morocco the situation has
      dramatically improved in the last few years as both the government and NGOs have
      become more aware of the importance and urgency of the issue. The incidence of
      cancer in patients under 15 years of age in Morocco is estimated to be 1000 new
      cases per year and the incidence of leukemia to be 100 new cases diagnosed per
      year. Pediatric cancer patients are mostly managed by public hospitals. Thus they
      are highly influenced by the Moroccan public health system, which is now
      considering cancer management a priority. Since health cover is very limited,
      most chemotherapy drugs were purchased by local parent associations. Recently, a
      new large Moroccan NGO (ALSC) provides anti-cancer drugs to all government-run
      oncology units. Despite all the progress, Morocco has witnessed in the pediatric
      oncology field, the palliative aspect of the care is not yet organized. Pediatric
      oncology is supported by the work of the National Society of Pediatric Oncolgy.
      The opioide therapy is available. However its use is strongly limited by the
      current restrictive and obsolete legislation which represents a major barrier to
      care. Despite the latest progress, pediatric oncology in Morocco still needs to
      improve in order to achieve performances comparable to those of the developed
      world. These improvements include better survival rates, less treatment
      abandonment, developing new techniques, improving quality of life and creating
      data collection teams. In order for this action to succeed all the stakeholders
      (government, NGOs, medical societies, oncology teams) must work together and
      coordinate their efforts.

PMID- 22357147
TI  - Pediatric oncology in Pakistan.
AB  - Pediatric oncology in Pakistan has developed over last decade with substantial
      increase in the facility for treatment and number of expertise. Though large
      numbers of children still do not reach treatment center more children have now
      access to quality cancer treatment. There has been gradual improvement in
      Pediatric oncology nursing and allied services. Pediatric Palliative care in
      Pakistan is in initial phase of development. Pediatric Oncology services are
      largely supported by philanthropists. Children Cancer Hospital a project of
      Children Cancer Foundation Pakistan Trust is not only providing quality treatment
      to every child regardless of paying ability but also playing a pivotal role in
      capacity building and creating awareness about childhood cancer in Pakistan.

PMID- 22357148
TI  - Current status of pediatric hematology/oncology and palliative care in Lebanon: a
      physician's perspective.
AB  - Children with cancer suffer a lot, especially those in developing countries with
      limited health resources. Although pediatric hematology/oncology has become a
      well-developed subspecialty in Lebanon, pediatric palliative care is still
      underrecognized. The current pediatric hematology/oncology and palliative care
      services in Lebanon are reviewed in this article. We stress upon the adverse
      consequences of absence of well-defined pediatric palliative care in order for it
      to be recognized and integrated as a new discipline.

PMID- 22357149
TI  - Patient-related barriers to cancer pain management in Jordan.
AB  - Barriers to cancer pain management are prevalent among cancer patients around the
      world, which may hinder patients from receiving adequate pain treatment. However,
      no study has examined the barriers to cancer pain management among Jordanian
      cancer patients and thus this study was conducted to fill this gap. Fifty cancer
      patients completed the Barriers Questionnaire. It was found that patients held
      high level of concerns (mean of Barriers Questionnaire = 2.58, SD = 0.54). In
      addition, fear of addiction, fear of physiological and harmful effects of pain
      medications were the highest rated items which may indicate the need for
      patients' education about cancer pain and its treatment.

PMID- 22357150
TI  - Pediatric oncology palliative care in Israel.
AB  - Pediatric Oncology in Israel has developed through the last 4 decades and
      currently outcome of children with cancer in Israel is similar to what is being
      achieved by international cooperative groups. Each year 450 children with cancer
      are being diagnosed and treated in specialized pediatric oncology centers. We
      describe the health care system and specifically focus on delay in diagnosis,
      late effects, palliative care and end of life issues. Finally we describe our
      achievements and list major challenges and future goals, in further improving
      patients care.

PMID- 22357151
TI  - A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor
      X.
AB  - We previously developed a hexon-specific PEGylated adenovirus (Ad) vector by
      utilizing avidin-biotin interaction. However, the Ad vector was aggregated due to
      the multiple interactions between avidin and biotin, resulting in a reduction in
      the transduction efficiencies in the organs following systemic administration. In
      this study, we developed a new method for hexon-specific PEGylation by mixing Ad
      vectors with PEGylated blood coagulation factor X (FX) (PEG-FX). FX specifically
      binds to the hexon protein, suggesting that FX serves as an adaptor molecule for
      hexon-specific modification. Intravenous administration of the PEG-FX-associated
      Ad (PEG-FX-Ad) vector into conventional mice resulted in prolonged blood
      retention. However, the transduction efficiencies in the liver were not reduced
      by PEG-FX. On the other hand, in the warfarinized mice, the PEG-FX-Ad vectors
      exhibited a significant reduction in the liver transduction. In addition,
      incubation of the PEG-FX-Ad vector with unmodified FX resulted in dissociation of
      PEG-FX from the Ad vector, indicating that a substitution of PEG-FX with
      endogenous FX occurs in the blood following administration. This study
      demonstrates that FX can be used as an adaptor molecule for hexon-specific
      modification; however, modified FX might be substituted with endogenous FX in the
      blood.

PMID- 22357153
TI  - Rambling and trembling in response to body loading.
AB  - Various studies have suggested that postural sway is controlled by at least two
      subsystems. Rambling-Trembling analysis is a widely accepted methodology to
      dissociate the signals generated by these two hypothetical subsystems. The core
      assumption of this method is based on the equilibrium point hypothesis which
      suggests that the central nervous system preserves upright standing by
      transiently shifting the center of pressure (COP) from one equilibrium point to
      another. The trajectory generated by this shifting is referred to as rambling and
      its difference from the original COP signal is referred to as trembling. In this
      study we showed that these two components of COP are differentially affected when
      standing with external loads. Using Detrended Fluctuation analysis, we compared
      the pattern of these two signals in different configurations of body loading. Our
      findings suggest that by applying an external load, the dynamics of the trembling
      component is altered independently of the area of postural sway and also
      independently of the rambling component. The dynamics of rambling changed only
      during the backloading condition in which the postural sway area also
      substantially increased. It can be suggested that during loaded standing, the
      trembling mechanism (which is suggested to be activated by peripheral mechanisms
      and reflexes) is altered without affecting the central influence on the shifts of
      the equilibrium point.

PMID- 22357152
TI  - Ruthenium-based complex nanocarriers for cancer therapy.
AB  - A new organometallic ruthenium complex, named AziRu, along with three amphiphilic
      nucleoside-based ruthenium complexes, ToThyRu, HoThyRu and DoHuRu, incorporating
      AziRu in their skeleton, have been synthesized, stabilized in POPC phospholipid
      formulations and studied for their antineoplastic activity. Self-aggregation
      behavior of these complexes was investigated, showing that the three synthesized
      AziRu derivatives able to form liposomes and, under specific conditions,
      elongated micelles. The formulations prepared in POPC proved to be stable for
      months and showed high in vitro antiproliferative activity. The here described
      results open new scenarios in the design of innovative transition metal-based
      supramolecular systems for anticancer drugs vectorization.

PMID- 22357154
TI  - Reducing the item number to obtain same-length self-assessment scales: a
      systematic approach using result of graphical loglinear Rasch modeling.
AB  - The Revised Danish Learning Styles Inventory (R-D-LSI) (Nielsen 2005), which is
      an adaptation of Sternberg-Wagner Thinking Styles Inventory (Sternberg, 1997),
      comprises 14 subscales, each measuring a separate learning style. Of these 14
      subscales, 9 are eight items long and 5 are seven items long. For self
      assessment, self-scoring and self-interpretational purposes it is deemed prudent
      that subscales measuring comparable constructs are of the same item length.
      Consequently, in order to obtain a self-assessment version of the R-D-LSI with an
      equal number of items in each subscale, a systematic approach to item reduction
      based on results of graphical loglinear Rasch modeling (GLLRM) was designed. This
      approach was then used to reduce the number of items in the subscales of the R-D
      LSI which had an item-length of more than seven items, thereby obtaining the
      Danish Self-Assessment Learning Styles Inventory (D-SA-LSI) comprising 14
      subscales each with an item length of seven. The systematic approach to item
      reduction based on results of GLLRM will be presented and exemplified by its
      application to the R-D-LSI.

PMID- 22357155
TI  - Using Rasch modeling to measure acculturation in youth.
AB  - Ethnic differences in health outcomes are assumed to reflect levels of
      acculturation, among other factors. Health surveys frequently include language
      and social interaction items taken from existing acculturation instruments. This
      study evaluated the dimensionality of responses to typical bilinear items in
      Latino youth using Rasch modeling. Two seven-item scales measuring Anglo-Hispanic
      orientation were adapted from Marin and Gamba (1996) and Cuellar, Arnold, and
      Maldonado (1995). Most of the items fit the Rasch model. However, there were gaps
      in both the Hispanic and Anglo scales. The Anglo items were not well targeted for
      the sample because most students reported they always spoke English. The lack of
      variability found in a heterogeneous sample of Latino youth has negative
      implications for the common practice of relying on language as a measure of
      acculturation. Acculturation instruments for youth probably need more sensitive
      items to discriminate linguistic differences, or to measure other factors.

PMID- 22357156
TI  - Measurement of mothers' confidence  to care for children assisted with
      tracheostomy technology in family homes.
AB  - The purpose of this research was to develop an objective, linear measure of
      mothers' confidence to care for children assisted with tracheostomy medical
      technology in their homes. Caregiver confidence is addressed in this research for
      three technologies, namely, a) trachesotomy, b) tracheostomy and ventilator, and
      c) BiPAP/CPAP although detailed measurement results are only reported for
      tracheostomy, and its co-calibration with tracheostomy and ventilator caregiving
      items. The sample consisted of 53 mothers responding to several caregiver
      questionnaires based on a caregiving task matrix after content and clinical
      validation. A major challenge was integrating this construct with overarching
      principles already established by Functional Caregiving, a multi-level humanistic
      caregiving model for children with intellectual disabilities. Empirical analyses
      included principal components analysis, and then linear transformation of
      Tracheostomy item ratings to an objective, equal-interval scale with a Rasch
      model. Results show caregiver separation on the Tracheostomy caregiving scale was
      2.66 and reliability, .88. In general, co-calibration improved measurement
      properties without affecting mothers' caregiving confidence measures. Although
      sample size was small, measuring mothers' confidence to care for a child
      supported by complex medical technologies appears very promising.

PMID- 22357157
TI  - Comparability of item quality indices  from sparse data matrices with random and
      non-random missing data patterns.
AB  - This article summarizes a simulation study of the performance of five item
      quality indicators (the weighted and unweighted versions of the mean square and
      standardized mean square fit indices and the point-measure correlation) under
      conditions of relatively high and low amounts of missing data under both random
      and conditional patterns of missing data for testing contexts such as those
      encountered in operational administrations of a computerized adaptive
      certification or licensure examination. The results suggest that weighted fit
      indices, particularly the standardized mean square index, and the point-measure
      correlation provide the most consistent information between random and
      conditional missing data patterns and that these indices perform more comparably
      for items near the passing score than for items with extreme difficulty values.

PMID- 22357158
TI  - The influence of labels associated with anchor points of Likert-type response
      scales in survey questionnaires.
AB  - Survey questionnaires are among the most used data gathering techniques in the
      social sciences researchers' toolbox and many factors can influence respondents'
      answers on items and affect data validity. Among these factors, research has
      accumulated which demonstrates that verbal and numeric labels associated with
      item's response categories in such questionnaire may influence substantially the
      way in which respondents operate their choices within the proposed response
      format. In line with these findings, the focus of this article is to use
      Andrich's Rating scale model to illustrate what kind of influence the quantifier
      adverb "totally," used to label or emphasize extreme categories, could have on
      respondents' answers.

PMID- 22357159
TI  - Analysis of letter name knowledge using Rasch measurement.
AB  - Letter name knowledge (LNK) is a key predictor of later reading ability and has
      been emphasized strongly in recent educational policy. Studies of LNK have
      implicitly treated it as a unidimensional construct with all letters equally
      relevant to its measurement. However, some empirical research suggests that
      contextual factors can affect the measurement of LNK. In this study, we analyze
      responses from 909 children on measures of LNK using the Rasch model and its
      extensions, and consider two contextual factors: the format of assessment and the
      own-name advantage, which states that children are more likely to know letters in
      their own first names. Results indicate that both contextual factors have
      important impacts on measurement and that LNK does not meet the requirements of
      Rasch measurement even when accounting for the contextual factors. These findings
      introduce philosophical concerns for measurement of constrained skills which have
      limited content for assessment.

PMID- 22357160
TI  - Converging on the tipping point:  a diagnostic methodology for standard setting.
AB  - This article discusses the strengths and weakness of the Angoff and Bookmark
      standard setting procedures. An alternative approach that focuses on the
      strengths of these procedures and adds three diagnostic indices is presented.
      This alternative approach is applied to three standard setting data sets and the
      results are discussed.

PMID- 22357161
TI  - Leucine supplementation chronically improves muscle protein synthesis in older
      adults consuming the RDA for protein.
AB  - BACKGROUND & AIM: Protein-energy supplementation is routinely employed to combat
      muscle loss. However, success is often compromised by increased satiety, poor
      palatability, high costs and low compliance. METHODS: For 2-weeks we supplemented
      meals of older individuals with leucine (4 g/meal; 3 meals/day; days 2-14).
      Metabolic studies were performed prior to (Day 1) and following (Day 15)
      supplementation. Leucine was not provided on metabolic study days. Venous blood
      and vastus lateralis muscle biopsies were obtained during a primed constant
      infusion of L-[ring-(13)C(6)] phenylalanine. Mixed muscle fractional synthesis
      rate (FSR), body composition and markers of nutrient signaling (mTOR, 4E-BP1 and
      p70S6K1 phosphorylation) were measured before and after a low
      protein/carbohydrate simulated meal. RESULTS: The meal modestly increased FSR on
      Day 1 (postabsorptive: 0.063 +/- 0.004 vs. postprandial: 0.075 +/- 0.006%/h; p =
      0.03), however, two weeks of leucine supplementation increased postabsorptive FSR
      (p = 0.004) and the response to the meal (p = 0.01) (postabsorptive: 0.074 +/-
      0.007 vs. postprandial: 0.10 +/- 0.007%/h). Changes in FSR were mirrored by
      increased phosphorylation of mTOR, 4E-BP1 and p70S6K1 (p <= 0.1). No change in
      fat free mass was observed (p > 0.05). CONCLUSIONS: In older adults, leucine
      supplementation may improve muscle protein synthesis in response to lower protein
      meals.

PMID- 22357162
TI  - Protein-based identification of quantitative trait loci associated with malignant
      transformation in two HER2+ cellular models of breast cancer.
AB  - BACKGROUND: A contemporary view of the cancer genome reveals extensive
      rearrangement compared to normal cells. Yet how these genetic alterations
      translate into specific proteomic changes that underpin acquiring the hallmarks
      of cancer remains unresolved. The objectives of this study were to quantify
      alterations in protein expression in two HER2+ cellular models of breast cancer
      and to infer differentially regulated signaling pathways in these models
      associated with the hallmarks of cancer. RESULTS: A proteomic workflow was used
      to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and
      SKBR3) that were differentially expressed relative to a normal human mammary
      epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1)
      proteins were uniquely identified that were differentially expressed by at least
      1.5-fold. Pathway inference tools were used to interpret these proteins in terms
      of functionally enriched pathways in the tumor cell lines. We observed "protein
      ubiquitination" and "apoptosis signaling" pathways were both enriched in the two
      breast cancer models while "IGF signaling" and "cell motility" pathways were
      enriched in BT474 and "amino acid metabolism" were enriched in the SKBR3 cell
      line. CONCLUSION: While "protein ubiquitination" and "apoptosis signaling"
      pathways were common to both the cell lines, the observed patterns of protein
      expression suggest that the evasion of apoptosis in each tumorigenic cell line
      occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via
      down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared
      to 184A1.

PMID- 22357163
TI  - Factors affecting amputation-free survival rates in critical limb ischemia.

PMID- 22357164
TI  - Interpretation of genome-wide infinium methylation data from ligated DNA in
      formalin-fixed, paraffin-embedded paired tumor and normal tissue.
AB  - BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) samples are a highly
      desirable resource for epigenetic studies, but there is no suitable platform to
      assay genome-wide methylation in these widely available resources. Recently,
      Thirlwell et al. (2010) have reported a modified ligation-based DNA repair
      protocol to prepare FFPE DNA for the Infinium methylation assay. In this study,
      we have tested the accuracy of methylation data obtained with this modification
      by comparing paired fresh-frozen (FF) and FFPE colon tissue (normal and tumor)
      from colorectal cancer patients. We report locus-specific correlation and
      concordance of tumor-specific differentially methylated loci (DML), both of which
      were not previously assessed. METHODS: We used Illumina's Infinium Methylation
      27K chip for 12 pairs of FF and 12 pairs of FFPE tissue from tumor and
      surrounding healthy tissue from the resected colon of the same individual, after
      repairing the FFPE DNA using Thirlwell's modified protocol. RESULTS: For both
      tumor and normal tissue, overall correlation of beta values between all loci in
      paired FF and FFPE was comparable to previous studies. Tissue storage type (FF or
      FFPE) was found to be the most significant source of variation rather than tissue
      type (normal or tumor). We found a large number of DML between FF and FFPE DNA.
      Using ANOVA, we also identified DML in tumor compared to normal tissue in both FF
      and FFPE samples, and out of the top 50 loci in both groups only 7 were common,
      indicating poor concordance. Likewise, while looking at the correlation of
      individual loci between FFPE and FF across the patients, less than 10% of loci
      showed strong correlation (r >= 0.6). Finally, we checked the effect of the
      ligation-based modification on the Infinium chemistry for SNP genotyping on an
      independent set of samples, which also showed poor performance. CONCLUSION:
      Ligation of FFPE DNA prior to the Infinium genome-wide methylation assay may
      detect a reasonable number of loci, but the numbers of detected loci are much
      fewer than in FF samples. More importantly, the concordance of DML detected
      between FF and FFPE DNA is suboptimal, and DML from FFPE tissues should be
      interpreted with great caution.

PMID- 22357165
TI  - Clinical management of adult sickle-cell disease.
AB  - PURPOSE OF REVIEW: This review provides an overview of the clinical management of
      sickle-cell disease (SCD) with recently published findings. RECENT FINDINGS:
      Unfortunately, negative observations did not confirm the hope that therapies
      acting on nitric oxide-cyclic GMP signaling, NSAIDs or Gardos channel inhibitor
      would control SCD vaso-occlusive crises. The safety of hydroxycarbamide was
      further supported by two observational studies covering 20 years and over 2 years
      in young children. Concerning the management of chronic visceral complications of
      SCD, the STOP II trial showed the risk of discontinuing blood exchange
      transfusion for children with transcranial Doppler-assessed accelerated blood
      flow velocities. The French multicenter Etendard study found that only 25% of SCD
      patients with tricuspid regurgitation velocity (TRV) 2.5 m/s or more on
      echocardiograms had catheterization-confirmed pulmonary hypertension. However,
      elevated TRV, regardless of its cause, was associated with higher mortality.
      Finally, recent results identified new therapeutic strategies for the treatment
      and prevention of renal dysfunction, priapism and skin ulcers, but prospective
      studies are needed to confirm those findings. SUMMARY: SCD treatment relies on
      concomitant preventive and curative measures to control its acute and chronic
      manifestations. Pathophysiologic advances have enabled better management, with
      new therapeutics highly likely in the near future.

PMID- 22357166
TI  - A single-dose, 3-way crossover pharmacokinetic comparison between immediate
      release oxycodone hydrochloride with aversion technology (IRO-A, Oxecta), IRO-a
      with Niacin, and Oxycodone Hydrochloride (Roxicodone) in healthy adults under
      fasting conditions.
AB  - Snorting and intravenous use are common routes of administration for advanced
      opioid abusers. A tablet form of immediate-release oxycodone (IRO) developed
      using Aversion Technology combines immediate release (IR) oxycodone HCl with
      inactive functional excipients that are intended to discourage tampering
      associated with intranasal and intravenous abuse (IRO-A; Oxecta, Pfizer). The
      purpose of this single-dose, open-label, randomized, 3-period, 3-treatment
      crossover study was to evaluate the bioequivalence of IRO-A to the marketed
      immediate-release oxycodone HCl (IRO; Roxicodone, Xanodyne Pharmaceuticals Inc.,
      Newport, KY). IRO-A was also compared with IRO-A with niacin, a product
      previously developed containing the same functional excipients plus niacin as an
      aversive agent to discourage oral overconsumption. Healthy adults (N = 40) aged
      18-55 years received single 15-mg doses of IRO-A, IRO-A with niacin (60 mg), or
      IRO after fasting overnight. Naltrexone was administered to diminish opioid
      effects. Doses were separated by a >=7-day washout. Plasma samples taken at
      designated time points were analyzed using liquid chromatography with tandem mass
      spectrometry. Geometric mean ratios for ln-transformed parameters for IRO-A and
      IRO were 92%, 104%, and 104% for Cmax, AUClast (AUC is area under the
      concentration-time curve), and AUCinf; 90% confidence intervals were within the
      accepted 80%-125% range. IRO-A was also bioequivalent to IRO-A with niacin.
      Adverse events were mild to moderate in intensity and typical of opioid therapy
      (nausea, headache, vomiting). Flushing only occurred when the subjects received
      the IRO-A with niacin treatment (9/37 subjects). The results demonstrated that
      IRO-A is bioequivalent to IRO and IRO-A with niacin. With features designed to
      discourage tampering associated with common forms of abuse, IRO-A may provide an
      alternative to conventional immediate-release oxycodone formulations. 

PMID- 22357167
TI  - Hyperprolactinemia with aripiprazole: understanding the paradox.
AB  - Aripiprazole, due to its partial agonist activity at the D2 receptors, is often
      recommended as the drug of choice in patients who develop antipsychotic-induced
      hyperprolactinemia. We report a case of a female patient who developed
      hyperprolactinemia while on treatment with aripiprazole. This partial D2
      agonistic activity of aripiprazole could be dose related, and hence, at higher
      doses, aripiprazole by itself can have dopamine antagonistic properties and hence
      cause prolactin system abnormalities. 

PMID- 22357168
TI  - Germ cell specific expression of Vasa in rare minnow, Gobiocypris rarus.
AB  - Germ cells are set aside early with somatic cells and take roles for reproduction
      of species from one generation to the next generation. Vasa, a member of DEAD
      family is well documented as germ cell marker in the animal kingdom. Rare minnow,
      Gobiocypris rarus, is an emerging model fish in China to study development and
      toxicology, etc. A suitable germ cell marker will benefit the studies of the
      factors that may influence germ cell development. Here, we report the cloning and
      characterization of G. rarus vasa named Grvas whose protein product has the
      typical characteristics of Vasa proteins. RT-PCR results showed that Grvas is
      expressed specifically in the gonads of male and female, it is maternally
      deposited into the eggs for embryos and is continuously expressed in the embryos
      from the zygote to larvae and adult. Grvas mRNA and/or protein is restricted to
      the germ cells of ovary and testis. Temporal expression of Grvas mRNA is similar
      to that of zebrafish vasa during embryogenesis. Grvas signals are coincident with
      primordial germ cells. These results mean that a germ cell marker, Grvas is
      isolated from rare minnow and its expression is exclusively in germ cells.

PMID- 22357169
TI  - Functional characterization of the adipokinetic hormone in the pea aphid,
      Acyrthosiphon pisum.
AB  - Aphids are important plant phloem-sucking pests and detailed knowledge about the
      hormonal control of their metabolism can potentially contribute to the
      development of methods for their management. The insect metabolism is
      predominantly controlled by neuropeptides belonging to the adipokinetic
      hormone/red pigment-concentrating hormone family (AKH/RPCH). The main goal of
      this study was to obtain the sequence of AKH transcripts and analyze its
      expression in all polyphenic female forms of the pea aphid, Acyrthosiphon pisum.
      The neuropeptide is expressed in the brain of all female forms and in the ovaries
      of the both (wingless and winged) parthenogenetic forms. The form of active Acypi
      AKH decapeptide was confirmed by the LC/MS and +ESI tandem mass spectrometry. The
      highest relative amount of Acypi-AKH was recorded in winged virginoparae.
      Furthermore, a potential role of this hormone when directly applied to the aphid
      was studied as well. Interestingly, no significant increase of trehalose in the
      wingless virginoparae after application of synthetic Acypi-AKH was detected. Yet
      this treatment did affect the level of protective polyol (mannitol) and
      furthermore led to increased activity of the detoxification enzyme glutathione S
      transferase. The possible physiological function of AKH in A. pisum under the
      stress conditions is discussed.

PMID- 22357170
TI  - Comparison of safety, renal function outcomes and efficacy of laparoscopic and
      percutaneous radio frequency ablation of renal masses.
AB  - PURPOSE: With the increased incidence of low stage renal cancers, thermal
      ablation technology has emerged as a viable treatment option. Current AUA
      (American Urological Association) guidelines include thermal ablation as a
      treatment modality for select individuals. We compared the laparoscopic and
      percutaneous approach for the radio frequency ablation of renal tumors under the
      guidance of urological surgeons. MATERIALS AND METHODS: We reviewed our radio
      frequency ablation database of patients with renal masses undergoing laparoscopic
      or computerized tomography guided percutaneous radio frequency ablation with
      simultaneous peripheral fiberoptic thermometry from November 2001 to January 2011
      at a single tertiary care center. Data were collected on patient demographics,
      and surgical and clinicopathological outcomes stratified by approach. RESULTS: A
      total of 298 patients with 316 renal tumors underwent laparoscopic (122 tumors)
      or computerized tomography guided (194 tumors) radio frequency ablation. There
      were no statistically significant differences between the laparoscopic and
      computerized tomography guided radio frequency ablation groups with respect to
      patient demographics, complication rates and renal functional outcomes (p>0.05).
      The 3-year Kaplan-Meier estimation of radiographic recurrence-free probability
      was 95% for computerized tomography guided radio frequency ablation and 94% for
      laparoscopic radio frequency ablation (p=0.84). Subanalysis of the 212 (67%)
      renal cell carcinoma tumors showed a 3-year Kaplan-Meier estimation of oncologic
      recurrence-free probability (post-ablation biopsy proven viable tumor) of 94% for
      computerized tomography guided radio frequency ablation and 100% for laparoscopic
      radio frequency ablation (p=0.16). Median followup was 21 months for laparoscopic
      radio frequency ablation) and 19 months for computerized tomography guided radio
      frequency ablation. CONCLUSIONS: Laparoscopic and computerized tomography guided
      radio frequency ablation appear safe and effective with statistically equivalent
      rates of complications and recurrence.

PMID- 22357171
TI  - Editorial comment.

PMID- 22357172
TI  - Neuropsychological measures of attention and impulse control among 8-year-old
      children exposed prenatally to organochlorines.
AB  - BACKGROUND: We previously reported associations between organochlorines and
      behaviors related to attention deficit hyperactivity disorder among boys and
      girls at 8 years of age using a teacher's rating scale for a birth cohort in New
      Bedford, Massachusetts (USA). OBJECTIVES: Our goal was to corroborate these
      findings using neuropsychological measures of inattentive and impulsive
      behaviors. METHODS: We investigated the association between cord serum
      polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethylene (p,p'
      DDE) and attention and impulse control using a Continuous Performance Test (CPT)
      and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC
      III). Participants came from a prospective cohort of children born during 1993
      1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median
      (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138,
      153, and 180 (SigmaPCB4)] and p,p'-DDE were 0.19 (0.01-2.59) and 0.31 (0-14.93)
      ng/g serum, respectively. RESULTS: We detected associations between PCBs and
      neuropsychological deficits for 578 and 584 children with CPT and WISC-III
      measures, respectively, but only among boys. For example, boys with higher
      exposure to SigmaPCB4 had a higher rate of CPT errors of omission [rate ratio for
      the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI):
      0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = 
      2.0; 95% CI: -3.5, -0.4). Weaker associations were found for p,p'-DDE. For girls,
      associations were in the opposite direction for the CPT and null for the WISC
      III. CONCLUSIONS: These results support an association between organochlorines
      (mainly PCBs) and neuropsychological measures of attention among boys only. Sex
      specific effects should be considered in studies of organochlorines and
      neurodevelopment.

PMID- 22357173
TI  - Donor morbidity including biliary complications in living-donor liver
      transplantation:  single-center analysis of 827 cases.
AB  - BACKGROUND: Because of the shortage of deceased-donor livers for transplantation,
      living-donor liver transplantation (LDLT) has become an indispensible treatment
      strategy for end-stage liver disease. The critical prerequisite for LDLT is the
      maximal safety of healthy donors. METHODS: From June 1996 to November 2010, a
      total of 827 completed donor hepatectomies were performed in our center. We
      analyzed donor morbidity associated with LDLT. RESULTS: There was no donor
      mortality. No complications were observed in 744 (90.0%) donors, and 83 (10.0%)
      donors experienced complications. Wound complications were most common, occurring
      in 48 (5.8%) patients. According to a modified Clavien classification, grade I,
      grade II, grade IIIa, and grade IIIb complications were experienced in 56
      (67.5%), 2 (2.4%), 15 (18.1%), and 10 (12.0%) donors, respectively. Surgical or
      interventional management was successful in all grade IIIa and grade IIIb donors.
      The incidence of biliary complications was significantly higher in younger
      donors. Donor morbidity did not decrease below the attained level even after time
      had passed. CONCLUSIONS: This study demonstrates the safety of donor hepatectomy.
      Complications were relatively minor and easily controlled. The incidence of
      biliary complications and donor age was inversely correlated. The procedural
      experience of the surgeons was not associated with the donor complication rate.

PMID- 22357174
TI  - Proteinuria following sirolimus conversion is associated with deterioration of
      kidney function in liver transplant recipients.
AB  - BACKGROUND: The role of sirolimus (SRL) conversion in the preservation of kidney
      function in liver transplant (LT) recipients with calcineurin inhibitor (CNI)
      nephrotoxicity is unclear. METHODS: Data on 102 LT recipients with deteriorating
      kidney function after CNI exposure who were later converted to SRL were
      retrospectively reviewed. Kidney function was assessed using serum creatinine and
      estimated glomerular filtration rate (eGFR) at time of conversion and serially
      thereafter. The primary endpoint was stabilization or improvement of kidney
      function as assessed by eGFR at last recorded follow-up compared with eGFR at the
      time of conversion. RESULT: After a median (interquartile range) of 3.1 (1.6-4.5)
      years of follow-up, serum creatinine decreased from 1.9 +/- 0.8 to 1.8 +/- 0.7
      mg/dL (P=0.25) and eGFR increased from 40.8 +/- 16.7 to 44.3 +/- 20.0 mL/min
      (P=0.03). During the same time period, 24-hr urinary protein excretion increased
      from median (interquartile range) of 72 (0-155) to 382 (169-999) mg/day
      (P=0.0001). Sixty-five (64%) patients achieved the primary endpoint and 37 (36%)
      experienced deterioration in kidney function. Independent predictors of
      deterioration of kidney function after SRL conversion were development of
      proteinuria >= 1000 mg/day (odds ratio [OR]: 3.3, confidence interval [CI]: 1.1
      9.5 P=0.03), post-LT diabetes (OR: 4.2, CI: 1.6-11.1, P=0.004), and higher eGFR
      at time of conversion (OR: 1.6, CI: 1.2-2.2, P=0.003). CONCLUSION: Improvement or
      stabilization of kidney function occurred in the majority of LT recipients
      converted to SRL for CNI nephrotoxicity. Proteinuria >= 1000 mg/day, post-LT
      diabetes, and higher baseline eGFR were independent predictors of kidney function
      loss after SRL conversion.

PMID- 22357175
TI  - Staphylococcus aureus bacteremia in solid organ transplant recipients:  evidence
      for improved survival when compared with nontransplant patients.
AB  - BACKGROUND: Staphylococcus aureus bacteremia (SAB) is an important cause of
      morbidity and mortality. Herein, we describe the incidence, clinical
      characteristics, and outcomes of SAB after solid organ transplantation (SOT) and
      compare these features with non-SOT controls. METHODS: In a single-center
      retrospective study, blood cultures positive for S. aureus were obtained from
      January 1, 2000, to December 31, 2008. Chart review was performed on all SOT
      recipients with SAB. The social security death index was used to determine all
      cause mortality. RESULTS: Seventy of 2959 patients with SAB were SOT recipients
      (26 lung, 19 liver, 18 kidney, and seven heart). The overall attack rate of SAB
      in SOT was 22.9/1000 transplant patients. Early-onset SAB (<= 90 days) was more
      frequent in liver recipients (79%), when compared with kidney recipients (17%).
      All-cause 30-day and 1-year mortality rates were 6% and 28% in SOT, respectively.
      Pneumonia as a source was associated with an increased 30-day mortality (18% vs.
      2%, P = 0.04). Comparing SOT versus non-SOT controls, methicillin resistance was
      more frequent (86% vs. 52%, P < 0.0001), and duration of bacteremia was longer
      (mean 3.8 vs. 1.6 days, P < 0.01). SOT status was independently associated with
      lower risk of 30-day mortality (risk ratio [RR]: 0.37, P = 0.02). CONCLUSIONS: In
      our cohort of SOT recipients, SAB was less common than previously reported and
      surprisingly had lower 30-day mortality, when compared with non-SOT. In SOT
      recipients, pneumonia as a source of SAB in SOT is associated with an increased
      30-day mortality.

PMID- 22357176
TI  - Immunomodulatory effect of nuclear factor-kappaB inhibition by
      dehydroxymethylepoxyquinomicin in combination with donor-specific blood
      transfusion.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key molecule in alloimmune
      responses, however, its role in tolerance induction is not clear. We have
      previously reported that dehydroxymethylepoxyquinomycin (DHMEQ), a novel NF
      kappaB inhibitor, prolongs cardiac allograft survival. In this study, we
      evaluated the immunomodulatory effects of DHMEQ when combined with a donor
      specific blood transfusion (DST), and assessed whether the treatment induces
      tolerance in a mouse heart transplantation model. METHODS: DST (20*10
      splenocytes) was given intravenously at day -7. DHMEQ (30 mg/kg/day) was
      administered intraperitoneally for 14 days after DST. Graft survival and
      histology were evaluated. The underlying mechanisms of immunomodulation by DST
      and DHMEQ treatments were investigated by assessing alloimmune responses after
      transplantation. RESULTS: In fully mismatched H2-to-H2 heart transplants, DST
      alone prolonged allograft median survival time to 15 days, whereas when DST was
      combined with DHMEQ treatment, the graft median survival time was prolonged to
      39.5 days. When the donor-recipient strain combination was reversed, that is, H2
      to-H2, heart transplants were accepted (>150 days survival) in more than 60% of
      recipients treated with a DST and DHMEQ, whereas control allografts were all
      rejected within 8 days. The combined therapy markedly inhibited immune responses
      by both the direct and indirect allorecognition pathways mainly attributed to
      promotion of activation-induced cell death and Treg generation. CONCLUSIONS: Our
      results demonstrate the distinctive ability of NF-kappaB inhibition in
      combination with donor alloantigen to promote transplantation tolerance through
      multiple cellular mechanisms.

PMID- 22357177
TI  - Sirolimus-associated testicular toxicity:  detrimental but reversible.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibition has been associated
      with gonadal dysfunction. The aim of this study was to characterize the effect of
      sirolimus (SRL) on male gonadal function in an experimental model. METHODS: Male
      Wistar rats were treated with intraperitoneal administration of vehicle or SRL.
      Vehicle group was treated for 12 weeks. Rats treated with SRL were killed at 4,
      8, and 12 weeks. A group of rats was treated with SRL for 4 weeks and then
      observed during 8 weeks to analyze the possible reversibility of the effect of
      mTOR inhibition. Body and testicular weight, testosterone, follicle-stimulating
      hormone level, and luteinizing hormone level were measured and testicular
      histology was analyzed including proliferation and apoptosis analysis. RESULTS:
      Testicular weight was significantly lower in all SRL groups. After SRL withdrawal
      testicular weight had partially recovered. The expression of steroidogenic acute
      regulatory protein decreased during SRL treatment, which could explain the
      reduction of testosterone levels, because steroidogenic acute regulatory protein
      is crucial for testosterone synthesis. Spermatogenesis was blocked on the
      spermatogonial level by SRL treatment. Withdrawal of SRL treatment led to
      complete recovery. CONCLUSIONS: mTOR inhibition in healthy animals produces
      sexual hormone dysfunction, seminiferous tubule dystrophy and spermatogenesis
      blockade. Furthermore, the spermatogenesis blockade produced by SRL is
      reversible.

PMID- 22357178
TI  - Can immune cell function assay identify patients at risk of infection or
      rejection? A meta-analysis.
AB  - BACKGROUND: The Cylex ImmuKnow cell function assay (CICFA) is being considered as
      a possible tool for identification of infection and rejection in transplant
      recipients. However, the predictive capability of CICFA is still unclear.
      METHODS: Herein, we performed a meta-analysis to assess the efficacy of CICFA in
      identifying risks of infection and rejection posttransplantation. After a careful
      review of eligible studies, sensitivity, specificity, and other measures of the
      accuracy of CICFA were pooled. Summary receiver operating characteristic curves
      were used to represent the overall test performance. RESULTS: Nine studies met
      the inclusion criteria. The pooled estimates for CICFA in identification of
      infection risk were poor, with a sensitivity of 0.58 (95% confidence interval
      [CI]: 0.52-0.64), a specificity of 0.69 (95% CI: 0.66-0.70), a positive
      likelihood ratio of 2.37 (95% CI: 1.90-2.94), a negative likelihood ratio of 0.39
      (95% CI: 0.16-0.70), and a diagnostic odds ratio of 7.41 (95% CI: 3.36-16.34).
      The pooled estimates for CICFA in identifying risk of rejection were also fairly
      poor with a sensitivity of 0.43 (95% CI: 0.34-0.52), a specificity of 0.75 (95%
      CI: 0.72-0.78), a positive likelihood ratio of 1.30 (95% CI: 0.74-2.28), a
      negative likelihood ratio of 0.96 (95% CI: 0.85-1.07), and a diagnostic odds
      ratio of 1.19 (95% CI: 0.65-2.20). CONCLUSION: The current evidence suggests that
      CICFA is not able to identify individuals at risk of infection or rejection.
      Additional studies are still needed to clarify the usefulness of this test for
      identifying risks of infection and rejection in transplant recipients.

PMID- 22357179
TI  - Complement activation and prognosis in patients with type 2 diabetes and
      myocardial infarction: a report from the DIGAMI 2 trial.
AB  - OBJECTIVE: The activation of the complement system may be involved in the
      pathology of myocardial infarction (MI) and type 2 diabetes. To explore their
      potential as prognostic markers, we characterized two factors in the complement
      cascade, the end product sC5b-9 and the mannose-binding lectin-associated Ser
      protease-2 (MASP-2), in type 2 diabetic patients with suspected MI. RESEARCH
      DESIGN AND METHODS: Plasma sC5b-9 and MASP-2 were determined in patients with MI
      and type 2 diabetes (n = 397; median age 70; male 68%). The adjudicated end
      points were cardiovascular events (CVEs), including cardiovascular mortality and
      nonfatal MI or stroke. RESULTS: The median sC5b-9 was 134 MUg/L (interquartile
      range [IQR] 101-190 MUg/L) and the median MASP-2 was 333 MUg/L (IQR 235-463
      MUg/L), with no significant correlation between them. Women had higher sC5b-9
      than men (median 152 vs. 130 MUg/L; P = 0.02). Both sC5b-9 and MASP-2 were
      correlated to age and creatinine clearance, while MASP-2 was also correlated to
      BMI. During a median follow-up of 2.4 years, CVEs occurred in 141 patients (36%).
      Both sC5b-9 (hazard ratio 1.37 [95% CI 1.13-1.65]; P < 0.01) and MASP-2 (0.68
      [0.51-0.92]; P = 0.01) predicted CVEs in unadjusted analyses. After multiple
      adjustments, the predictive capacity remained for sC5b-9 (1.30 [1.02-1.66]; P =
      0.04) but not for MASP-2. CONCLUSIONS: In type 2 diabetic patients with MI, high
      levels of sC5b-9 predict future CVE. This indicates that the complement system
      may play a significant role in the pathology of the subsequent myocardial damage
      and that the pathways leading to complement activation warrant further
      exploration as potential therapeutic targets to improve the prognosis for these
      patients.

PMID- 22357180
TI  - Metabolic consequences of hepatic steatosis in overweight and obese adolescents.
AB  - OBJECTIVE: To test the hypothesis that hepatic steatosis is associated with risk
      factors for type 2 diabetes in overweight and obese youth, mediated by
      cardiorespiratory fitness. RESEARCH DESIGN AND METHODS: This was a cross
      sectional study comparing insulin sensitivity between 30 overweight and obese
      adolescents with hepatic steatosis, 68 overweight and obese adolescents without
      hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis.
      Cardiorespiratory fitness was determined by a graded maximal exercise test on a
      cycle ergometer. Secondary outcomes included presence of metabolic syndrome and
      glucose response to a 75-g oral glucose challenge. RESULTS: The presence of
      hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02)
      and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences
      in insulin sensitivity (3.5 vs. 4.5 mU ? kg(-1) ? min(-1), P = 0.03), prevalence
      of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve
      (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and
      visceral fat. The association between hepatic steatosis and insulin sensitivity
      (beta = -0.24, t = -2.29, P < 0.025), metabolic syndrome (beta = -0.54, t = -5.8,
      P < 0.001), and glucose area under the curve (beta = 0.33, t = 3.3, P < 0.001)
      was independent of visceral and whole-body adiposity. Cardiorespiratory fitness
      was not associated with hepatic steatosis, insulin sensitivity, or presence of
      metabolic syndrome. CONCLUSIONS: Hepatic steatosis is associated with type 2
      diabetes risk factors independent of cardiorespiratory fitness, whole-body
      adiposity, and visceral fat mass.

PMID- 22357181
TI  - Diabetes screening among immigrants: a population-based urban cohort study.
AB  - OBJECTIVE: To examine diabetes screening, predictors of screening, and the burden
      of undiagnosed diabetes in the immigrant population and whether these estimates
      differ by ethnicity. RESEARCH DESIGN AND METHODS: A population-based
      retrospective cohort linking administrative health data to immigration files was
      used to follow the entire diabetes-free population aged 40 years and up in
      Ontario, Canada (N = 3,484,222) for 3 years (2004-2007) to determine whether
      individuals were screened for diabetes. Multivariate regression was used to
      determine predictors of having a diabetes test. RESULTS: Screening rates were
      slightly higher in the immigrant versus the general population (76.0 and 74.4%,
      respectively; P < 0.001), with the highest rates in people born in South Asia,
      Mexico, Latin America, and the Caribbean. Immigrant seniors (age >=65 years) were
      screened less than nonimmigrant seniors. Percent yield of new diabetes subjects
      among those screened was high for certain countries of birth (South Asia, 13.0%;
      Mexico and Latin America, 12.1%; Caribbean, 9.5%) and low among others (Europe,
      Central Asia, U.S., 5.1-5.2%). The number of physician visits was the single most
      important predictor of screening, and many high-risk ethnic groups required
      numerous visits before a test was administered. The proportion of diabetes that
      remained undiagnosed was estimated to be 9.7% in the general population and 9.0%
      in immigrants. CONCLUSIONS: Overall diabetes-screening rates are high in Canada's
      universal health care setting, including among high-risk ethnic groups. Despite
      this finding, disparities in screening rates between immigrant subgroups persist
      and multiple physician visits are often required to achieve recommended screening
      levels.

PMID- 22357182
TI  - Insulin sensitivity, beta-cell function, and incretin effect in individuals with
      elevated 1-hour postload plasma glucose levels.
AB  - OBJECTIVE: Individuals with normal glucose tolerance (NGT), whose 1-h postload
      plasma glucose is >=155 mg/dL (NGT 1h-high), have an increased risk of type 2
      diabetes. The purpose of this study was to characterize their metabolic
      phenotype. RESEARCH DESIGN AND METHODS: A total of 305 nondiabetic offspring of
      type 2 diabetic patients was consecutively recruited. Insulin secretion was
      assessed using both indexes derived from oral glucose tolerance test (OGTT) and
      intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by
      hyperinsulinemic-euglycemic clamp. RESULTS: Compared with individuals with a 1-h
      postload plasma glucose <155 mg/dL (NGT 1h-low), NGT 1h-high individuals
      exhibited lower insulin sensitivity after adjustment for age, sex, and BMI.
      Insulin secretion estimated from the OGTT did not differ between the two groups
      of individuals. By contrast, compared with NGT 1h-low individuals, the acute
      insulin response during an IVGTT and the disposition index were significantly
      reduced in NGT 1h-high individuals after adjustment for age, sex, and BMI.
      Incretin effect, estimated as the ratio between total insulin responses during
      OGTT and IVGTT, was higher in NGT 1h-high individuals compared with NGT 1h-low
      individuals. CONCLUSIONS: NGT 1h-high individuals may represent an intermediate
      state of glucose intolerance between NGT and type 2 diabetes characterized by
      insulin resistance and reduced beta-cell function, the two main
      pathophysiological defects responsible for the development of type 2 diabetes.
      Postload hyperglycemia is the result of an intrinsic beta-cell defect rather than
      impaired incretin effect.

PMID- 22357183
TI  - Heart rate variability and sensorimotor polyneuropathy in type 1 diabetes.
AB  - OBJECTIVE: Reduced heart rate variability (HRV) is classically viewed as an early
      phenomenon in diabetic sensorimotor polyneuropathy (DSP). We aimed to determine
      the characteristics of HRV across the spectrum of clinical DSP in type 1
      diabetes. RESEARCH DESIGN AND METHODS: Eighty-nine diabetic subjects and 60
      healthy volunteers underwent assessment of RR interval variation (RR(var)) during
      deep breathing and clinical and electrophysiological examination. We examined the
      distribution of age-standardized RR(var) across the spectrum of clinical DSP,
      identified variables associated with RR(var) in multivariate regression, and
      compared RR(var) with validated measures of neuropathy. RESULTS: Age-standardized
      RR(var) had a significant, step-wise, inverse relationship with ordinal
      categories of increasing DSP severity (beta = -5.4, P < 0.0001) among subjects
      with diabetes. Case subjects with DSP had substantially lower age-standardized
      RR(var) compared with diabetic control subjects without DSP (beta = -5.2, P <
      0.01), although there was substantial overlap of RR(var) between diabetic case
      subjects and control subjects and the healthy volunteer cohort. In multivariate
      analysis, advanced age was independently associated with lower RR(var) in both
      healthy volunteers and diabetic subjects, whereas higher glycated hemoglobin
      A(1c) and systolic blood pressure were independently associated with lower
      RR(var) in diabetic subjects. RR(var) had a significant association with
      validated measures of large and small fiber neuropathy. CONCLUSIONS: HRV may be a
      biomarker for clinical DSP and is associated cross-sectionally with both early
      and late measures of neuropathy. The low HRV observed in some control subjects
      without DSP and in most case subjects with severe DSP may signify that HRV has
      different prognostic implications in these groups, requiring further longitudinal
      study.

PMID- 22357184
TI  - Validation of diabetic retinopathy and maculopathy diagnoses recorded in a U.K.
      primary care database.
AB  - OBJECTIVE: To describe the validity of recorded diabetic retinopathy (DR) and
      diabetic maculopathy (DMP) diagnoses, including edema (DMO) in The Health
      Improvement Network (THIN) database. RESEARCH DESIGN AND METHODS: In two
      independent computer searches, we detected 20,838 patients with diabetes aged 1
      84 years with a first DR computer Read entry in 2000-2008 and 4,064 with a first
      DMP entry. A two-step strategy was used to validate both outcomes as follows: 1)
      review of patient profiles including free-text comments from primary care
      practitioners (PCPs) (containing referral information and test results) of a
      random sample of 500 DR and all DMP computer-detected patients. We classified
      them in probable, possible, and noncase according to the diagnosis plausibility
      based on the manual review of the computerized information; and 2) review of
      questionnaires sent by PCPs and medical records in a random sample (N = 200 for
      each outcome including 36 diabetic macular edema [DMO]). Gold standard was PCPs'
      confirmation. RESULTS: After profiles review, we categorized 418 as
      probable/possible DR. In addition, 3,676 DMP were categorized as
      probable/possible (including 711 DMO). After review of information sent by PCPs,
      confirmation rates were 87.3 and 87.2%, respectively (90.3% for DMO). When we
      applied them to the whole sample of computer-detected patients, the weighted
      confirmation rate was 78.0% for DR and 78.8% for DMP (86.2% for DMO).
      CONCLUSIONS: Read codes for DR, DM, and DMO are moderately accurate in
      identifying incident case subjects of these ophthalmologic complications. The
      validity improved when incorporating PCPs' text comments to the patient's
      profile. THIN database proved to be a valuable resource to study ophthalmological
      diabetes complications.

PMID- 22357185
TI  - Safety and efficacy of once-weekly exenatide compared with insulin glargine
      titrated to target in patients with type 2 diabetes over 84 weeks.
AB  - OBJECTIVE: We recently reported that after 26 weeks, exenatide once weekly (EQW)
      resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight
      loss compared with daily insulin glargine (IG) in patients with type 2 diabetes
      who were taking metformin alone or with sulfonylurea. This 84-week extension
      study assessed the long-term safety and efficacy of EQW versus IG. RESEARCH
      DESIGN AND METHODS: This multicenter, open-label, randomized, two-arm, parallel
      trial assessed change in A1C, proportions of patients achieving A1C <7.0 and
      <=6.5%, body weight, incidence of hypoglycemia, and overall safety. RESULTS: Of
      415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered
      the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by -1.2% for
      EQW vs. -1.0% for IG (P = 0.029). The proportions of patients who achieved end
      point A1C targets <7.0 and <=6.5% were 44.6% for EQW patients vs. 36.8% for IG
      patients (P = 0.084) and 31.3% for EQW patients vs. 20.2% for IG patients (P =
      0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas
      those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus
      sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs.
      54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8%
      for EQW patients vs. 32% for IG patients (P < 0.001). Among adverse events
      occurring in >=5% of patients, diarrhea and nausea occurred more frequently (P <
      0.05) in the EQW group than in the IG group (12 vs. 6% and 15 vs. 1%,
      respectively). CONCLUSIONS: After 84 weeks, patients treated with EQW continued
      to experience better glycemic control with sustained overall weight loss and a
      lower risk of hypoglycemia than patients treated with IG.

PMID- 22357186
TI  - Arterial stiffness is increased in patients with type 1 diabetes without
      cardiovascular disease: a potential role of low-grade inflammation.
AB  - OBJECTIVE: To investigate the relationship between arterial stiffness and low
      grade inflammation in subjects with type 1 diabetes without clinical
      cardiovascular disease. RESEARCH DESIGN AND METHODS: Sixty-eight patients with
      type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated.
      Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum
      concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)
      6, and soluble fractions of tumor necrosis factor-alpha receptors 1 and 2
      (sTNFalphaR1 and sTNFalphaR2, respectively) were measured. All statistical
      analyses were stratified by sex. RESULTS: Subjects with diabetes had a higher
      aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001;
      women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after
      adjusting for cardiovascular risk factors. Men with diabetes had higher
      concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P
      = 0.002), sTNFalphaR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFalphaR2 (2,774
      vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations
      of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated
      positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008),
      whereas in women with diabetes no significant correlation was found. In men,
      multiple linear regression analysis showed that the following variables were
      associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade
      inflammation (R(2) = 0.543). In women, these variables were age, BMI, mean
      arterial pressure, and type 1 diabetes (R(2) = 0.550). CONCLUSIONS: Arterial
      stiffness assessed as aPWV is increased in patients with type 1 diabetes without
      clinical cardiovascular disease, independently of classical cardiovascular risk
      factors. In men with type 1 diabetes, low-grade inflammation is independently
      associated with arterial stiffness.

PMID- 22357187
TI  - The hyperglycemia and adverse pregnancy outcome study: associations of GDM and
      obesity with pregnancy outcomes.
AB  - OBJECTIVE: To determine associations of gestational diabetes mellitus (GDM) and
      obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse
      Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS: Participants
      underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM
      was diagnosed post hoc using International Association of Diabetes and Pregnancy
      Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were
      measured. Adverse pregnancy outcomes included birth weight, newborn percent body
      fat, and cord C-peptide >90th percentiles, primary cesarean delivery,
      preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT.
      Multiple logistic regression was used to examine associations of GDM and obesity
      with outcomes. RESULTS: Mean maternal BMI was 27.7, 13.7% were obese (BMI >=33.0
      kg/m(2)), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women,
      odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93-2.47),
      for obesity alone 1.73 (1.50-2.00), and for both GDM and obesity 3.62 (3.04
      4.32). Results for primary cesarean delivery and preeclampsia and for cord C
      peptide and newborn percent body fat >90th percentiles were similar. Odds for
      birth weight >90th percentile were progressively greater with both higher OGTT
      glucose and higher maternal BMI. There was a 339-g difference in birth weight for
      babies of obese GDM women, compared with babies of normal/underweight women
      (64.2% of all women) with normal glucose based on a composite OGTT measure of
      fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women).
      CONCLUSIONS: Both maternal GDM and obesity are independently associated with
      adverse pregnancy outcomes. Their combination has a greater impact than either
      one alone.

PMID- 22357188
TI  - Increased toll-like receptor activity in patients with metabolic syndrome.
AB  - OBJECTIVE: The metabolic syndrome (MetS) is highly prevalent and confers an
      increased risk for diabetes and cardiovascular disease (CVD). While MetS is a
      proinflammatory state, there is a paucity of data on cellular inflammation in
      MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of
      the innate immune response. RESEARCH DESIGN AND METHODS: The aim of this study
      was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD
      and control subjects since both of the receptors have been implicated in
      atherosclerosis and insulin resistance. Fasting blood was obtained for TLR
      expression and activity. RESULTS: Circulating levels of high-sensitivity C
      reactive protein, interleukin (IL)-1beta, IL-6, IL-8, and soluble tumor necrosis
      factor receptor 1 (sTNFR1) were significantly increased in MetS versus control
      subjects following adjustment for waist circumference. There was a significant
      increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after
      adjustment for waist circumference. In addition to increased nuclear factor
      kappaB nuclear binding, there was significantly increased release of IL-1beta, IL
      6, and IL-8 in MetS versus control subjects following priming of the monocytes
      with lipopolysaccharides. While both plasma free fatty acids and endotoxin were
      increased in MetS, they correlated significantly with TLR4 only. CONCLUSIONS: In
      conclusion, we make the novel observation that both TLR2 and TLR4 expression and
      activity are increased in the monocytes of patients with MetS and could
      contribute to increased risk for diabetes and CVD.

PMID- 22357189
TI  - The accuracy benefit of multiple amperometric glucose sensors in people with type
      1 diabetes.
AB  - OBJECTIVE: To improve glucose sensor accuracy in subjects with type 1 diabetes by
      using multiple sensors and to assess whether the benefit of redundancy is
      affected by intersensor distance. RESEARCH DESIGN AND METHODS: Nineteen adults
      with type 1 diabetes wore four Dexcom SEVEN PLUS subcutaneous glucose sensors
      during two 9-h studies. One pair of sensors was worn on each side of the abdomen,
      with each sensor pair placed at a predetermined distance apart and 20 cm away
      from the opposite pair. Arterialized venous blood glucose levels were measured
      every 15 min, and sensor glucose values were recorded every 5 min. Sensors were
      calibrated once at the beginning of the study. RESULTS: The use of four sensors
      significantly reduced very large errors compared with one sensor (0.4 vs. 2.6% of
      errors >=50% from reference glucose, P < 0.001) and also improved overall
      accuracy (mean absolute relative difference, 11.6 vs. 14.8%, P < 0.001). Using
      only two sensors also significantly improved very large errors and accuracy.
      Intersensor distance did not affect the function of sensor pairs. CONCLUSIONS:
      Sensor accuracy is significantly improved with the use of multiple sensors
      compared with the use of a single sensor. The benefit of redundancy is present
      even when sensors are positioned very closely together (7 mm). These findings are
      relevant to the design of an artificial pancreas device.

PMID- 22357190
TI  - The utility of ultrasound and magnetic resonance imaging versus surgery for the
      characterization of mullerian anomalies in the pediatric and adolescent
      population.
AB  - STUDY OBJECTIVE: To evaluate the utility of transabdominal ultrasound and
      magnetic resonance imaging in the evaluation of American Society for Reproductive
      Medicine (?)(ASRM)-classified mullerian anomalies compared to surgical findings
      in the pediatric and adolescent population. DESIGN: Retrospective chart review.
      SETTING: Tertiary academic center. PARTICIPANTS: Thirty-eight patients with
      mullerian anomalies seen in our pediatric and adolescent gynecology clinic were
      identified both on the basis of ICD-9 codes and having magnetic resonance imaging
      at Texas Children's Hospital between 2004 and 2009. INTERVENTIONS: None. MAIN
      OUTCOMES MEASURE: Correlation among transabdominal ultrasound and magnetic
      resonance imaging findings with surgical findings. RESULTS: Mean age was 12.2 (+/
      4.1) years. Twenty-eight patients underwent magnetic resonance imaging and
      required surgical intervention, and 88.5% demonstrated correlative consistency
      with surgical findings. Twenty-two patients underwent ultrasound, magnetic
      resonance imaging, and surgery, which revealed consistency among ultrasound and
      surgical findings (59.1%) and consistency among magnetic resonance imaging and
      surgical findings (90.9%). In ASRM diagnoses evaluated by magnetic resonance
      imaging, surgical findings correlated in 92% (Pearson 0.89). Overall, 55.2% of
      patients had a renal malformation. CONCLUSIONS: Magnetic resonance imaging is the
      gold standard imaging modality for mullerian anomalies and is an effective
      technique for noninvasive evaluation and accurate classification of the type of
      anomaly in the pediatric and adolescent population. Magnetic resonance imaging
      should be considered as an adjunct to transabdominal ultrasound to evaluate
      mullerian anomalies.

PMID- 22357191
TI  - A complete gonadal dysgenesis case with mental retardation, congenital hip
      dislocation, severe vertebra rotoscoliosis, pectus excavatus, and spina bifida
      occulta.
AB  - BACKGROUND: 46,XY, or Swyer syndrome, is a complete gonadal dysgenesis. Patients
      usually presents with primary amenorrhea with underdeveloped secondary sex
      characteristics. Phenotypes of these patients are female. In this report, a Swyer
      syndrome case is reported with novel clinical features that are classified as
      connective tissue disorders. This case and the 2 other previously reported Swyer
      syndrome cases with ascendant aortic aneurysm and diaphragmatic hernia are
      suggest that the Y chromosome has an important role in the structure of
      connective tissue. CASE: Here we report a case of a 17-year-old with clinical
      features of 46,XY complete gonadal dysgenesis including external female
      genitalia, hypoplastic uterus, hypergonadotrophic hypogonadism, incomplete
      secondary sex characterics, primary amenorrhea, and normal male karyotype. In
      addition, she had mild mental retardation, severe rotoscoliosis, pectus
      excavatus, spina bifida occulta, hip dislocation, and long, slender extremities.
      She had a rudimentary uterus and streak gonads; after giving her cyclic estrogen
      and progesterone pills, she was able to menstruate. SUMMARY AND CONCLUSION: In
      this report, a Swyer syndrome case was discussed regarding clinical features,
      especially those are not characteristic for Swyer syndrome after a review of the
      literature.

PMID- 22357192
TI  - Development of six PROMIS pediatrics proxy-report item banks.
AB  - BACKGROUND: Pediatric self-report should be considered the standard for measuring
      patient reported outcomes (PRO) among children. However, circumstances exist when
      the child is too young, cognitively impaired, or too ill to complete a PRO
      instrument and a proxy-report is needed. This paper describes the development
      process including the proxy cognitive interviews and large-field-test survey
      methods and sample characteristics employed to produce item parameters for the
      Patient Reported Outcomes Measurement Information System (PROMIS) pediatric proxy
      report item banks. METHODS: The PROMIS pediatric self-report items were converted
      into proxy-report items before undergoing cognitive interviews. These items
      covered six domains (physical function, emotional distress, social peer
      relationships, fatigue, pain interference, and asthma impact). Caregivers (n =
      25) of children ages of 5 and 17 years provided qualitative feedback on proxy
      report items to assess any major issues with these items. From May 2008 to March
      2009, the large-scale survey enrolled children ages 8-17 years to complete the
      self-report version and caregivers to complete the proxy-report version of the
      survey (n = 1548 dyads). Caregivers of children ages 5 to 7 years completed the
      proxy report survey (n = 432). In addition, caregivers completed other proxy
      instruments, PedsQLTM 4.0 Generic Core Scales Parent Proxy-Report version,
      PedsQLTM Asthma Module Parent Proxy-Report version, and KIDSCREEN Parent-Proxy
      52. RESULTS: Item content was well understood by proxies and did not require item
      revisions but some proxies clearly noted that determining an answer on behalf of
      their child was difficult for some items. Dyads and caregivers of children ages 5
      17 years old were enrolled in the large-scale testing. The majority were female
      (85%), married (70%), Caucasian (64%) and had at least a high school education
      (94%). Approximately 50% had children with a chronic health condition, primarily
      asthma, which was diagnosed or treated within 6 months prior to theinterview. The
      PROMIS proxy sample scored similar or better on the other proxy instruments
      compared to normative samples. CONCLUSIONS: The initial calibration data was
      provided by a diverse set of caregivers of children with a variety of common
      chronic illnesses and racial/ethnic backgrounds. The PROMIS pediatric proxy
      report item banks include physical function (mobility n = 23; upper extremity n =
      29), emotional distress (anxiety n = 15; depressive symptoms n = 14; anger n =
      5), social peer relationships (n = 15), fatigue (n = 34), pain interference (n =
      13), and asthma impact (n = 17).

PMID- 22357193
TI  - Implementation and evaluation of peer assessment of clinical skills for first
      year student nurses.
AB  - Enabling student nurses to learn and develop evidence-based clinical skills is
      the cornerstone of nursing education programmes. This article describes the
      implementation of a peer assessment scheme for clinical skills within a skills
      laboratory in a university school of nursing, and the link between peer
      assessment and clinical skills development. This was a qualitative evaluative
      study that used questionnaires for data collection and was undertaken on one
      cohort of students. Findings showed that nearly half of all the statements made
      by students were about the positive impact of PACS on their skills learning.
      Students identified giving and receiving peer feedback, reflection and working
      with peers in small groups as being particularly valuable in clinical skills
      learning. Increased confidence was also a dominant finding as was the value of
      repeated practice in a simulation setting on skills development. This study
      supports some of the previous literature related to use of simulation and peer
      assessment but the discussion presented in this article also highlights that the
      findings of this study contradicts other findings in the literature. What makes
      this study unique is its contribution to the literature is the link that was
      established by students between the peer-assessment process and clinical skills
      learning.

PMID- 22357194
TI  - Molecular evidence for natural killer-like cells in equine endometrial cups.
AB  - OBJECTIVES: To identify equine orthologs of major NK cell marker genes and
      utilize them to determine whether NK cells are present among the dense
      infiltration of lymphocytes that surround the endometrial cup structures of the
      horse placenta during early pregnancy. STUDY DESIGN: PCR primers were developed
      to detect the equine orthologs of NKP46, CD16, CD56, and CD94; gene expression
      was detected in RNA isolated from lymphocytes using standard 2-step reverse
      transcriptase (RT) PCR and products were cloned and sequenced. Absolute real-time
      RT-PCR was used to quantitate gene expression in total, CD3+, and CD3- peripheral
      lymphocytes, and invasive trophoblast. Lymphocytes surrounding the endometrial
      cups (ECL) of five mares in early pregnancy were isolated and NK marker gene
      expression levels were assayed by quantitative RT-PCR. MAIN OUTCOME MEASURES:
      Absolute mRNA transcript numbers were determined by performing quantitative RT
      PCR and comparing values to plasmid standards of known quantities. RESULTS: NKP46
      gene expression in peripheral CD3- lymphocytes was higher than in CD3+
      lymphocytes, CD16 levels were higher in the CD3+ population, and no significant
      differences were detected for CD56 and CD94 between the two groups. Expression of
      all four NK cell markers was significantly higher in lymphocytes isolated from
      the endometrial cups of pregnant mares compared to PBMC isolated from the same
      animal on the same day (NKP46, 14-fold higher; CD94, 8-fold higher; CD16, 20-fold
      higher; CD56, 44-fold higher). CONCLUSIONS: These data provide the first evidence
      for the expression of major NK cell markers by horse cells and an enrichment of
      NK-like cells in the equine endometrium during pregnancy.

PMID- 22357195
TI  - Prospective evaluation of multiparametric ultrasound and quantitative
      elastosonography in the differential diagnosis of benign and malignant thyroid
      nodules: preliminary experience.
AB  - PURPOSE: To assess the clinical value of quantitative elastosonography compared
      with multiparametric ultrasound in differentiating the nature of thyroid nodules.
      METHODS AND MATERIALS: Ninety-seven consecutive patients (32 males, 65 females,
      mean age, 54 years, range 20-81 years) with thyroid nodules previously detected
      at color-Doppler ultrasound (CDUS), were prospectively examined with
      elastosonography with dedicated quantitative software (Elasto-Q, Toshiba) before
      surgery. Ultrasound examination and elastosonography were evaluated by two
      investigators in consensus. US features, color-Doppler pattern, and strain ratio
      value were evaluated. Sensitivity and specificity of CDUS and sono-elastography
      were compared using X(2) test and ROC curves. RESULTS: Sensitivity and
      specificity of hypoechogenicity, irregular margins or suspicious halo features,
      CDUS blood flow pattern, and strain ratio in the diagnosis of malignant nodules
      were 56.8%, 62.2%, 54.1% and 97.3% and 71.7%, 93.3%, 28.3%, and 91.7%,
      respectively. Elastosonography was more sensitive and specific than all
      ultrasonographic features in predicting malignancy of the thyroid nodules
      (p<0.0001). According to elastosonographic features the lesions characterized by
      strain ratio >= 2 were highly likely to be of malignant nature (p<0.0001, O.R.
      396, 95%, CI: 44-3530). CONCLUSIONS: The results of the present study suggest
      that elastosonography with Q system is a valuable tool in the characterization of
      thyroid nodules and it seems to be far more accurate than CDUS. These findings as
      well as those of previous studies support its use in selecting patients who are
      candidates for surgery.

PMID- 22357196
TI  - Reply to letter to the editor: magnetic resonance as an alternative imaging
      method for the evaluation of patients with pulmonary hypertension.

PMID- 22357197
TI  - Life in (and on) the rocks.

PMID- 22357198
TI  - What history tells us. XXVII. A new life for allostery.

PMID- 22357199
TI  - Sequence periodic pattern of HERV LTRs: a matrix simulation algorithm.
AB  - Flanking regulatory long terminal repeats (LTRs) in Human endogenous retrovirus
      (HERV) is a kind of typical DNA repeat that is widespread in the human genome.
      Currently, many algorithms have been developed to detect the latent periodicity
      of a wide range of DNA repeats. However, no such attempt was made for HERV LTRs.
      The present study focused on the investigation of the possible sequence periodic
      patterns in the HERV LTRs and their regulatory mechanisms. We calculated the
      sequence periods of 5', 3' and combined LTRs in HERVs with our devised matrix
      simulation algorithm. It is interesting that 5' and 3' LTRs have the same period
      of 7, and combined LTRs have a period of 9. These results indicated that HERV
      LTRs have predominant periodic patterns. Based on the obtained sequence
      periodicity, we constructed periodic consensus sequences of 5', 3' and combined
      LTRs. As to 5' and 3' LTRs with the same period - 7, we manually scanned the
      nucleotide bases in the corresponding positions of their periodic consensus
      sequences, and found some positions have the nucleotide base unchanged, such as
      the 1st, 5th and 7th positions. These conservative nucleotide base positions
      represent critical binding sites of regulatory LTRs, and may be indicative of
      conserved regulatory mechanisms in LRT-participating regulatory networks.

PMID- 22357200
TI  - Accumulation of rare earth elements by siderophore-forming Arthrobacter luteolus
      isolated from rare earth environment of Chavara, India.
AB  - In this study, Arthrobacter luteolus, isolated from rare earth environment of
      Chavara (Quilon district, Kerala, India), were found to produce catechol-type
      siderophores. The bacterial strain accumulated rare earth elements such as
      samarium and scandium. The siderophores may play a role in the accumulation of
      rare earth elements. Catecholate siderophore and low-molecular-weight organic
      acids were found to be present in experiments with Arthrobacter luteolus. The
      influence of siderophore on the accumulation of rare earth elements by bacteria
      has been extensively discussed.

PMID- 22357201
TI  - TP53 codon 72 polymorphism in pigmentary phenotypes.
AB  - The p53 protein exerts different cellular functions, and recent findings have
      demonstrated its influence on the cascade of skin pigmentation during UV
      exposure. Among TP53 gene polymorphisms, the most studied is the G to C
      transversion in exon 4 at codon 72, which results in three distinct genotypes,
      Arg/Arg, Pro/Pro and Arg/Pro, each one encoding different p53 isoforms.
      Therefore, this study aimed to determine the relationship between TP53 codon 72
      polymorphism and skin protection against sunburn. Genomic DNA was extracted from
      peripheral blood samples and genotyping was performed by PCR and confirmed by
      restriction enzyme digestion. The genotype frequency was 50% for Arg/Arg and
      14.6% for Pro/Pro genotype. The frequency of heterozygous subjects was 35.4%. In
      our population, p53 genotypes were in Hardy-Weinberg (HW) equilibrium (X2 HM less
      than 3.84), showing a predominance of arginine allele (total Arg allele frequency
      of 68%). No significant association between p53 genotype and skin colour, hair or
      eye colour and susceptibility to sun exposure was found. However, further
      analysis demonstrated a significant association between the genotype Pro/Pro and
      blue/green eyes among participants who presented redness (P=0.016). Our findings
      indicate susceptibility to sun exposure when this phenotype (eye colour) occurs
      simultaneously with Pro/Pro genotype.

PMID- 22357202
TI  - Mitogen-activated protein kinases mediate Mycobacterium tuberculosis-induced CD44
      surface expression  in monocytes.
AB  - CD44, an adhesion molecule, has been reported to be a binding site for
      Mycobacterium tuberculosis (M. tuberculosis) in macrophages and it also mediates
      mycobacterial phagocytosis, macrophage recruitment and protective immunity
      against pulmonary tuberculosis in vivo. However, the signalling pathways that are
      involved in M. tuberculosis-induced CD44 surface expression in monocytic cells
      are currently unknown. Exposure of THP-1 human monocytes to M. tuberculosis H37Rv
      and H37Ra induced distinct, time-dependent, phosphorylation of mitogen-activated
      protein kinase kinase-1, extracellular signal regulated kinase 1/2, mitogen
      activated protein kinase kinase 3/6, p38 mitogen-activated protein kinase and c
      jun N-terminal kinases. The strains also differed in their usage of CD14 and
      human leukocyte antigen-DR (HLA-DR) receptors in mediating mitogen-activated
      protein kinase activation. M. tuberculosis H37Rv strain induced lower CD44
      surface expression and tumour necrosis factor-alpha levels, whereas H37Ra the
      reverse. Using highly specific inhibitors of mitogen-activated protein kinase
      kinase-1, p38 mitogen-activated protein kinase and c-jun N-terminal kinase, we
      report that inhibition of extracellular signal regulated kinase 1/2 and c-jun N
      terminal kinases increases, but that inhibition of p38 mitogen-activated protein
      kinase decreases M. tuberculosis-induced CD44 surface expression in THP-1 human
      monocytes.

PMID- 22357203
TI  - Aged mice have increased inflammatory monocyte concentration and altered
      expression of cell-surface functional receptors.
AB  - The expression of monocyte cell-surface receptors represents one index of immune
      dysfunction, which is common with aging. Although mouse models of aging are
      prevalent, monocyte subset assessment is rare. Our purpose was to compare cell
      receptor expression on classic (CD115+/Gr-1 high) and non-classic (CD115+/Gr-1
      low) monocytes from 80- or 20-week-old CD-1 mice. Three-colour flow cytometry was
      used to determine the concentration of monocyte subsets and their respective cell
      surface expression of TLR2, TLR4, CD80, CD86, MHC II and CD54. These receptors
      were selected because they have been previously associated with altered monocyte
      function. Data were analysed with independent t-tests; significance was set at P
      less than 0.05. Old mice had a greater concentration of both classic (258%,
      P=0.003) and non-classic (70%, P=0.026) monocytes. The classic : non-classic
      monocyte ratio doubled in old as compared with that in young mice (P=0.006),
      indicating a pro-inflammatory shift. TLR4 ( 27%, P=0.001) and CD80 ( 37%,
      P=0.004) were decreased on classic monocytes from old as compared with those from
      young mice. TLR2 ( 24%, P=0.002) and MHCII ( 21%, P=0.026) were altered on non
      classic monocytes from old as compared with those from young mice. The increased
      classic : non-classic monocyte ratio combined with changes in the cell-surface
      receptor expression on both monocyte subsets is indicative of immune dysfunction,
      which may increase age-associated disease risk.

PMID- 22357204
TI  - High prevalence of oncogenic HPV-16 in cervical smears of asymptomatic women of
      eastern Uttar Pradesh, India: a population-based study.
AB  - In developing countries like India, occurrence of Human papillomavirus (HPV) in
      cervical cancer as well as in the asymptomatic population was observed to be very
      high. Studies on HPV prevalence have been conducted in different parts of the
      country but no data were available from the eastern region of Uttar Pradesh (UP).
      The present study aimed to determine the status of HPV prevalence and its
      association with different socio-demographic factors in this population.
      Prevalence of HPV was investigated in a total of 2424 cervical scrape samples of
      asymptomatic women. Primer sets from L1 consensus region of viral genome were
      used to detect the presence of HPV, and the positive samples were genotyped by
      sequencing. Univariate binary logistic regression analysis was used to evaluate
      association of socio-demographic factors with HPV. 9.9% of the clinically
      asymptomatic women were found to be infected with HPV comprising 26 different
      genotypes. Among HPV-positive women, 80.8% showed single infection, while 15.4%
      harboured multiple infections. HPV-16 (63.7%) was the most prevalent, followed by
      HPV-31 (6.7%), HPV-6 (5.4%), HPV-81 (4.6%) and HPV-33 (4.2%). Significant
      association of HPV with non-vegetarian diet (P less than 0.05) and rural
      residential areas (P less than 0.01) were observed. High prevalence of HPV-16 in
      asymptomatic women of this population, a frequency comparable to invasive
      cervical cancers, highlights an urgent need for a therapeutic HPV vaccine
      covering HPV-16 and other high-risk types to provide protection against the
      disease.

PMID- 22357205
TI  - Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell
      lines.
AB  - Phenoxodiol is an isoflavone derivative that has been shown to elicit cytotoxic
      effects against a broad range of human cancers. We examined the effect of
      phenoxodiol on cell death pathways on the prostate cell lines LNCaP, DU145 and
      PC3, representative of different stages of prostate cancer, and its effects on
      cell death pathways in these cell lines. Cell proliferation assays demonstrated a
      significant reduction in the rate of cell proliferation after 48 h exposure to
      phenoxodiol (10 and 30 MUM). FACS analysis and 3'-end labelling indicated that
      all three prostate cancer cell lines underwent substantial levels of cell death
      48 h after treatment. Mitochondrial membrane depolarization, indicative of early
      stage cell death signalling, using JC-1 detection, was also apparent in all cell
      lines after exposure to phenoxodiol in the absence of caspase-3 activation.
      Caspase inhibition assays indicated that phenoxodiol operates through a caspase
      independent cell death pathway. These data demonstrate that phenoxodiol elicits
      anti-cancer effects in prostate cancer cell lines representative of early and
      later stages of development through an as-yet-unknown cell death mechanism. These
      data warrant the further investigation of phenoxodiol as a potential treatment
      for prostate cancer.

PMID- 22357206
TI  - Differential expression of ZFX gene in gastric cancer.
AB  - Gastric cancer accounts for 8% of the total cancer cases and 10% of total cancer
      deaths worldwide. In Iran, gastric cancer is the leading cause of national cancer
      related mortality. Most human cancers show substantial heterogeneity. The cancer
      stem cell (CSC) hypothesis has been proposed to reconcile this heterogeneity. ZFX
      encodes a member of the krueppel C2H2-type zinc-finger protein family that is
      required as a transcriptional regulator for self-renewal of stem cells. A total
      of 30 paired tissue gastric samples were examined for ZFX gene expression by
      quantitative real-time RT-PCR. Although the relative expression of the gene was
      significantly high in 47% of the examined tumour tissues, its expression was low
      in the others (53%). There was a statistically significant association between
      the ZFX gene expression and different tumour types and grades. This is the first
      report that shows ZFX was differentially expressed in gastric cancer. Of note, it
      was overexpressed in diffused-type and grade III gastric tumoural tissues. Due to
      this, ZFX may have the potential to be used as a target for therapeutic
      interventions.

PMID- 22357207
TI  - Leptin regulates proliferation and apoptosis of colorectal carcinoma through
      PI3K/Akt/mTOR signalling  pathway.
AB  - Epidemiological studies have indicated that obesity is associated with colorectal
      cancer. The obesity hormone leptin is considered as a key mediator for cancer
      development and progression. The present study aims to investigate regulatory
      effects of leptin on colorectal carcinoma. The expression of leptin and its
      receptor Ob-R was examined by immunohistochemistry in 108 Chinese patients with
      colorectal carcinoma. The results showed that leptin/Ob-R expression was
      significantly associated with T stage, TNM stage, lymph node metastasis, distant
      metastasis, differentiation and expression of p-mTOR, p-70S6 kinase, and p-Akt.
      Furthermore, the effects of leptin on proliferation and apoptosis of HCT-116
      colon carcinoma cells were determined. The results showed that leptin could
      stimulate the proliferation and inhibit the apoptosis of HCT-116 colon cells
      through the PI3K/Akt/mTOR pathway. Ly294002 (a PI3K inhibitor) and rapamycin (an
      mTOR inhibitor) could prevent the regulatory effects of leptin on the
      proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated
      PI3K/Akt/mTOR pathway. All these results indicated that leptin could regulate
      proliferation and apoptosis of colorectal carcinoma through the PI3K/Akt/ mTOR
      signalling pathway.

PMID- 22357208
TI  - Expression, purification and characterization of the interferon-inducible,
      antiviral and tumour-suppressor protein, human RNase L.
AB  - The interferon (IFN)-inducible, 2',5'-oligoadenylate (2-5A)-dependent
      ribonuclease L (RNase L) plays key role in antiviral defense of mammalian cells.
      Induction by IFN and activation by double-stranded RNA lead to 2-5A cofactor
      synthesis, which activates RNase L by causing its dimerization. Active RNase L
      degrades single-stranded viral as well as cellular RNAs causing apoptosis of
      virus-infected cells. Earlier, we had reported that expression of recombinant
      human RNase L caused RNA-degradation and cell-growth inhibition in E. coli
      without the need for exogenous 2-5A. Expression of human RNase L in E. coli
      usually leads to problems of leaky expression, low yield and degradation of the
      recombinant protein, which demands number of chromatographic steps for its
      subsequent purification thereby, compromising its biochemical activity. Here, we
      report a convenient protocol for expression of full-length, soluble and
      biochemically active recombinant human RNase L as GST-RNase L fusion protein from
      E. coli utilizing a single-step affinity purification with an appreciable yield
      of the highly purified protein. Recombinant RNase L was characterized by SDS
      PAGE, immunoblotting and MALDI-TOF analysis. A semi-quantitative agarose-gel
      based ribonuclease assay was developed for measuring its 2-5A-dependent RNase L
      activity against cellular large rRNAs as substrates. The optimized expression
      conditions minimized degradation of the protein, making it a convenient method
      for purification of RNase L, which can be utilized to study effects of various
      agents on the RNase L activity and its protein-protein interactions.

PMID- 22357209
TI  - Corticoadrenal activity in rat regulates betaine-homocysteine S-methyltransferase
      expression with opposite effects in liver and kidney.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) is an enzyme that converts
      homocysteine (Hcy) to methionine using betaine as a methyl donor. Betaine also
      acts as osmolyte in kidney medulla, protecting cells from high extracellular
      osmolarity. Hepatic BHMT expression is regulated by salt intake. Hormones,
      particularly corticosteroids, also regulate BHMT expression in rat liver. We
      investigated to know whether the corticoadrenal activity plays a role in kidney
      BHMT expression. BHMT activity in rat kidneys is several orders of magnitude
      lower than in rat livers and only restricted to the renal cortex. This study
      confirms that corticosteroids stimulate BHMT activity in the liver and, for the
      first time in an animal model, also up-regulate the BHMT gene expression.
      Besides, unlike the liver, corticosteroids in rat kidney down-regulate BHMT
      expression and activity. Given that the classical effect of adrenocortical
      activity on the kidney is associated with sodium and water re-absorption by the
      distal tubule leading to volume expansion, by promoting lesser use of betaine as
      a methyl donor, corticosteroids would preserve betaine for its other role as
      osmoprotectant against changes in the extracellular osmotic conditions. We
      conclude that corticosteroids are, at least in part, responsible for the
      inhibition of BHMT expression and activity in rat kidneys.

PMID- 22357211
TI  - Development of transgenic finger millet (Eleusine coracana (L.) Gaertn.)
      resistant to leaf blast  disease.
AB  - Finger millet plants conferring resistance to leaf blast disease have been
      developed by inserting a rice chitinase (chi11) gene through Agrobacterium
      mediated transformation. Plasmid pHyg-Chi.11 harbouring the rice chitinase gene
      under the control of maize ubiquitin promoter was introduced into finger millet
      using Agrobacterium strain LBA4404 (pSB1). Transformed plants were selected and
      regenerated on hygromycin-supplemented medium. Transient expression of transgene
      was confirmed by GUS histochemical staining. The incorporation of rice chitinase
      gene in R0 and R1 progenies was confirmed by PCR and Southern blot analyses.
      Expression of chitinase gene in finger millet was confirmed by Western blot
      analysis with a barley chitinase antibody. A leaf blast assay was also performed
      by challenging the transgenic plants with spores of Pyricularia grisea. The
      frequency of transient expression was 16.3% to 19.3%. Stable frequency was 3.5%
      to 3.9%. Southern blot analysis confirmed the integration of 3.1 kb chitinase
      gene. Western blot analysis detected the presence of 35 kDa chitinase enzyme.
      Chitinase activity ranged from 19.4 to 24.8. In segregation analysis, the
      transgenic R1 lines produced three resistant and one sensitive for hygromycin,
      confirming the normal Mendelian pattern of transgene segregation. Transgenic
      plants showed high level of resistance to leaf blast disease compared to control
      plants. This is the first study reporting the introduction of rice chitinase gene
      into finger millet for leaf blast resistance.

PMID- 22357210
TI  - Transient expression of Human papillomavirus type 16 L2 epitope fused to N- and C
      terminus of coat  protein of Potato virus X in plants.
AB  - Transient expression of foreign genes based on plant viral vectors is a suitable
      system for the production of relevant immunogens that can be used for the
      development of a new generation of vaccines against a variety of infectious
      diseases. In the present study the epitope derived from HPV-16 L2 minor capsid
      protein (amino acids 108-120) was expressed from Potato virus X (PVX)-based
      vector pGR106 as N- or C-terminal fusion with the PVX coat protein (PVX CP) in
      transgenic Nicotiana benthamiana plants. The fusion protein L2 108-120-PVX CP was
      successfully expressed in plants at a level of 170 mg/kg of fresh leaf tissue.
      The C-terminal fusion protein PVX CP- L2 108-120 was expressed using mutated
      vector sequence to avoid homologous recombination at a level of 8 mg/kg of fresh
      leaf tissue. Immunogenicity of L2 108-120-PVX CP virus-like particles was tested
      after immunization of mice by subcutaneous injection or tattoo administration. In
      animal sera the antibodies against the PVX CP and the L2 108-120 epitope were
      found after both methods of vaccine delivery.

PMID- 22357212
TI  - Molecular cytogenetic identification of a novel dwarf wheat line with
      introgressed Thinopyrum ponticum  chromatin.
AB  - Novel dwarfing germplasms and dwarfing genes are valuable for the wheat breeding.
      A novel semi-dwarf line, 31505-1, with reduced height compared with its common
      wheat parent, was derived from a cross between common wheat and Thinopyrum
      ponticum. Cytological studies demonstrated that 31505-1 contained 42 chromosomes
      and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization
      (GISH) analysis showed that 31505-1 had no large Th. ponticum chromosome
      fragments. Fluorescence in situ hybridization (FISH) results revealed the absence
      of a pAs1 hybridization band on 2DL chromosome of 31505-1. Two SSR markers
      (Xwmc41 and Xcfd168) and two STS markers (Xmag4059 and Xmag3596), which were
      located on 2D chromosome, amplified unique bands of Th. Ponticum in 31505-1.
      These revealed presence of an introgressed Th. ponticum segment in 2DL chromosome
      of dwarf line 31505-1, although the alien segment could not be detected by GISH.

PMID- 22357213
TI  - Autophagy: a double-edged sword in Alzheimer's disease.
AB  - Autophagy is a major protein degradation pathway that is essential for stress
      induced and constitutive protein turnover. Accumulated evidence has demonstrated
      that amyloid-beta (A beta) protein can be generated in autophagic vacuoles,
      promoting its extracellular deposition in neuritic plaques as the pathological
      hallmark of Alzheimer's disease (AD). The molecular machinery for A beta
      generation, including APP, APP-C99 and beta-/gamma-secretases, are all enriched
      in autophagic vacuoles. The induction of autophagy can be vividly observed in the
      brain at early stages of sporadic AD and in an AD transgenic mouse model.
      Accumulated evidence has also demonstrated a neuroprotective role of autophagy in
      mediating the degradation of aggregated proteins that are causative of various
      neurodegenerative diseases. Autophagy is thus widely regarded as an intracellular
      hub for the removal of the detrimental A beta peptides and Tau aggregates.
      Nonetheless, compelling data also reveal an unfavorable function of autophagy in
      facilitating the production of intracellular A beta. The two faces of autophagy
      on the homeostasis of A beta place it in a very unique and intriguing position in
      AD pathogenesis. This article briefly summarizes seminal discoveries that are
      shedding new light on the critical and unique roles of autophagy in AD and
      potential therapeutic approaches against autophagy-elicited AD.

PMID- 22357216
TI  - The effect of muscle fatigue on position sense in an upper limb multi-joint task.
AB  - The purpose of this study was to estimate the extent to which muscle fatigue can
      impact on the position sense in the upper limb. Twelve healthy volunteers were
      asked to do a reaching task while grasping a wooden block and match the block's
      position with a corresponding target displayed on a flat screen, without vision.
      Following that, subjects performed resistive exercises with Thera-band strips
      until fatigue was induced and then the position sense task was repeated. A
      significant change in the endpoint position was observed after fatigue, in the
      up/down direction (p <= .001). The variability of endpoint positions in up/down
      direction was also significantly increased after fatigue (p <=.03). There was no
      significant change in endpoint orientation but there was a significant fatigue *
      orientation effect on endpoint rotational variability. In a follow-up experiment,
      a group of subjects repeated the same protocol, but with a period of quiet rest
      between the two position sense tasks. In that group, there were no differences in
      endpoint position, orientation or variability. Muscle fatigue is an important
      factor that should be taken into consideration during the treatment of
      musculoskeletal injuries as well as athletic training.

PMID- 22357214
TI  - Recent advances in development of marker-free transgenic plants: regulation and
      biosafety concern.
AB  - During the efficient genetic transformation of plants with the gene of interest,
      some selectable marker genes are also used in order to identify the transgenic
      plant cells or tissues. Usually, antibiotic- or herbicide-selective agents and
      their corresponding resistance genes are used to introduce economically valuable
      genes into crop plants. From the biosafety authority and consumer viewpoints, the
      presence of selectable marker genes in released transgenic crops may be
      transferred to weeds or pathogenic microorganisms in the gastrointestinal tract
      or soil, making them resistant to treatment with herbicides or antibiotics,
      respectively. Sexual crossing also raises the problem of transgene expression
      because redundancy of transgenes in the genome may trigger homology-dependent
      gene silencing. The future potential of transgenic technologies for crop
      improvement depends greatly on our abilities to engineer stable expression of
      multiple transgenic traits in a predictable fashion and to prevent the transfer
      of undesirable transgenic material to non-transgenic crops and related species.
      Therefore, it is now essential to develop an efficient marker-free transgenic
      system. These considerations underline the development of various approaches
      designed to facilitate timely elimination of transgenes when their function is no
      longer needed. Due to the limiting number of available selectable marker genes,
      in future the stacking of transgenes will be increasingly desirable. The
      production of marker-free transgenic plants is now a critical requisite for their
      commercial deployment and also for engineering multiple and complex trait. Here
      we describe the current technologies to eliminate the selectable marker genes
      (SMG) in order to develop marker-free transgenic plants and also discuss the
      regulation and biosafety concern of genetically modified (GM) crops.

PMID- 22357217
TI  - Genetic investigation for adults with intellectual disability:  opportunities and
      challenges.
AB  - PURPOSE OF REVIEW: This review discusses diagnostic genetic assessment for adults
      with idiopathic intellectual disability, considering the potential yields and
      limitations of currently available investigations. RECENT FINDINGS: Genome-wide
      microarray analysis is now a routine diagnostic test. Estimated yields for
      clinically significant copy number variants in adults with idiopathic
      intellectual disability are at least 10%. The medical and neuropsychiatric
      phenotypes of recurrent genomic disorders are being established. Many single gene
      causes of intellectual disability have been identified, most notably for X-linked
      intellectual disability. Ascribing causality, determination of recurrence risk,
      and prognostication for rare or unique variants remain challenging. SUMMARY:
      Clinical evaluation and investigations (both nongenetic and genetic) can yield an
      aetiological diagnosis for a growing proportion of individuals with intellectual
      disability. Not all adults with intellectual disability will ever have received
      such an assessment. Genetic diagnosis can provide an explanation for lifelong
      disabling cognitive disorder, guide prognosis, and highlight medical
      comorbidities. A key outcome is clarification of recurrence risk and facilitation
      of reproductive choices. However, there are limited data on the desirability and
      acceptability of genetic diagnosis amongst adult patients with intellectual
      disability and their families, and concern that ethical principles and practices
      may be changing without scrutiny. The decision to embark on diagnostic review
      requires careful consideration for each individual.

PMID- 22357215
TI  - Embryonal cancers in Europe.
AB  - Embryonal cancers are a heterogeneous group of rare cancers which mainly occur in
      children and adolescents. The aim of the present study was to estimate the burden
      (incidence, prevalence, survival and proportion of cured) for the principal
      embryonal cancers in Europe (EU27), using population-based data from cancer
      registries (CRs) participating in RARECARE. We identified 3322 cases diagnosed
      from 1995 to 2002 (latest period for which data are available): 44%
      neuroblastoma, 35% nephroblastoma, 13% retinoblastoma and 6% hepatoblastoma. Very
      few cases of pulmonary blastoma (43 cases) and pancreatoblastoma (seven cases)
      were diagnosed. About 2000 new embryonal cancers were estimated every year in
      EU27, for an annual incidence rate of 4 per million (1.8 neuroblastoma, 1.4
      nephroblastoma, and 0.5 retinoblastoma); 91% of cases occurred in patients under
      15 years. Five-year relative survival for all embryonal cancers was 80% (99%
      retinoblastoma, 90% nephroblastoma, 71% hepatoblastoma and 68% neuroblastoma).
      Overall survival was lower in adolescents and adults than in those under 15
      years. The cure rate was estimated at 80%. Slightly less than 40,000 persons were
      estimated alive in EU27 with a diagnosis of embryonal cancer in 2008.
      Nephroblastoma was the most prevalent (18,150 cases in EU27), followed by
      neuroblastoma (12,100), retinoblastoma (5200), hepatoblastoma (2700) and
      pulmonary blastoma (614). This is the first study to delineate the embryonal
      cancer burden in Europe by age, sex and European region. Survival/cure rate is
      generally high, but there are considerable gaps in our understanding of the
      natural histories of these rare diseases particularly in adults.

PMID- 22357219
TI  - Elimination of Rhodnius prolixus in Central America.
AB  - Rhodnius prolixus is one of the main vectors of Trypanosoma cruzi, causative
      agent of Chagas disease. In Central America, it was first discovered in 1915 in
      El Salvador, from where it spread northwest to Guatemala and Mexico, and
      southeast to Nicaragua and Costa Rica, arriving also in Honduras in the late
      1950s. Indoor residual spraying (IRS) by the antimalaria services of Costa Rica
      prevented its spread southwards, and similar IRS programmes appear to have
      eliminated it from El Salvador by the late 1970s. In 1997, by resolution of the
      Ministers of Health of the seven Central American countries, a multinational
      initiative against Chagas disease (IPCA) was launched with one of the specific
      objectives being the elimination of R. prolixus from the region. As a result,
      more and more infested areas were encountered, and progressively sprayed using an
      IRS strategy already deployed against Triatoma infestans in the southern cone
      countries of South America. In 2008, Guatemala became the first of these
      countries to be formally certified as free of Chagas disease transmission due to
      R. prolixus. The other infested countries have since been similarly certified,
      and none of these has reported the presence of R. prolixus since June 2010.
      Further surveillance is required, but current evidence suggests that R. prolixus
      may now been eliminated from throughout the mesoamerican region, with a
      corresponding decline in the incidence of T. cruzi infections.

PMID- 22357218
TI  - Human induced pluripotent stem cells and neurodegenerative disease:  prospects
      for novel therapies.
AB  - PURPOSE OF REVIEW: The lack of effective treatments for various neurodegenerative
      disorders has placed huge burdens on society. We review the current status in
      applying induced pluripotent stem cell (iPSC) technology for the cellular
      therapy, drug screening, and in-vitro modeling of neurodegenerative diseases.
      RECENT FINDINGS: iPSCs are generated from somatic cells by overexpressing four
      reprogramming factors (Oct4, Sox2, Klf4, and Myc). Like human embryonic stem
      cells, iPSCs have features of self-renewal and pluripotency, and allow in-vitro
      disease modeling, drug screening, and cell replacement therapy. Disease-specific
      iPSCs were derived from patients of several neurodegenerative diseases, including
      Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and
      spinal muscular atrophy. Neurons differentiated from these iPSCs recapitulated
      the in-vivo phenotypes, providing platforms for drug screening. In the case of
      Parkinson's disease, iPSC-derived dopaminergic neurons gave positive therapeutic
      effect on a rodent Parkinson's disease model as a proof of principle in using
      iPSCs as sources of cell replacement therapy. Beyond iPSC technology, much effort
      is being made to generate neurons directly from dermal fibroblasts with neuron
      specific transcription factors, which does not require making iPSCs as an
      intermediate cell type. SUMMARY: We summarize recent progress in using iPSCs for
      modeling the progress and treatment of neurodegenerative diseases and provide
      evidence for future perspectives in this field.

PMID- 22357220
TI  - Sorafenib in combination with ionizing radiation has a greater anti-tumour
      activity in a breast cancer model.
AB  - High expression of vascular endothelial growth factor (VEGF) in patients with
      breast cancer has been associated with a poor prognosis, indicating that VEGF
      could be linked to the efficacy of chemotherapy and radiotherapy. It has also
      been suggested that radiation resistance is partly due to tumour cell production
      of angiogenic cytokines, particularly VEGF receptor (VEGFR). This evidence
      indicates that inhibition of VEGFR might enhance the radiation response.
      Sorafenib tosylate (Bay 54-9085) is an oral, small-molecule multikinase inhibitor
      of several targets including RAF/MEK/ERK MAP kinase signalling, VEGFR-2, VEGFR-3
      and platelet-derived growth factor receptor-beta. Sorafenib has shown clinical
      efficacy in treating solid tumours such as renal cell and hepatocellular
      carcinomas. However, strategies are yet to be identified to prolong and maximize
      the anticancer effect of this multikinase inhibitor. The objective of this study
      was to determine whether a combination of Sorafenib and radiation will enhance
      the treatment response in vitro and in vivo. Radio-modulating effect of Sorafenib
      was assessed by performing clonogenic assays. In addition, cell cycle analyses as
      well as annexin-V apoptosis assays were performed 24 and 48 h after treatment,
      respectively. To confirm our in-vitro results, tumour growth delay assays were
      performed. Our results showed a strong and supra-additive antitumour effect of
      radiation combined with Sorafenib in vitro (dose enhancement factor of 1.76). The
      combined therapy demonstrated a strong and significant G2/M cell cycle arrest
      (combined treatment vs. irradiated alone: P<0.0008). Moreover, annexin-V staining
      showed a significant increase in the level of apoptosis (combined treatment vs.
      irradiated alone: P<0.0004). Study of the syngeneic model demonstrated the
      superior potency of the Sorafenib combined with radiotherapy. Our results
      demonstrate that higher antitumour activity can be achieved when radiation and
      Sorafenib are combined.

PMID- 22357223
TI  - New noninvasive ultrasound techniques: can they predict liver cirrhosis?
AB  - OBJECTIVE: This study aimed to determine the threshold values and accuracy of 2
      noninvasive techniques, contrast-enhanced ultrasound with maximum-intensity
      projection (MIP) imaging and ultrasound elastography, acoustic radiation force
      impulse (ARFI), to differentiate a normal from a cirrhotic liver. MATERIALS AND
      METHODS: One hundred thirty-two patients were predicted clinically as having a
      normal liver (n = 60) or cirrhosis (n = 72). All had MIP liver vessel evaluation
      on an Acuson Sequoia and 90 of them had ARFI on an S2000 (Siemens, Mountain View,
      Calif). Two readers reviewed 4 parameters on MIP data and predicted cirrhosis (n
      = 65) or normal (n = 67) outcome. They were considered as having cirrhosis when
      more than 1 MIP parameter was positive. Acoustic radiation force impulse values
      above 1.36 m/s suggested cirrhosis. Receiver operating characteristic curve
      analysis was performed to evaluate the diagnostic accuracy of the ARFI
      measurement and to extract the optimal cutoff value in the differentiation of a
      cirrhotic liver from a noncirrhotic liver. RESULTS: Sixty-four patients (64/65,
      98.5%) with abnormal and 8 (8/59, 13.6%) with normal vessels on MIP imaging were
      clinically cirrhosis (P < 0.001). Forty-five patients (45/49, 91.8%) with
      abnormal ARFI (>= 1.36 m/s) and 6 (6/41, 14.6%) with normal ARFI (<1.36 m/s) had
      a clinical cirrhotic liver (P < 0.001). Sensitivity and specificity of MIP of
      vessel morphology to predict cirrhosis were 89% (64/72) and 98% (59/60),
      respectively. Acoustic radiation force impulse showed a sensitivity of 88%
      (45/51) and a specificity of 90% (35/39), and the area under the receiver
      operating characteristic curve was 0.932, suggesting very good accuracy. The
      combination of ARFI and MIP showed increased sensitivity and specificity to 95.8%
      and 100%. CONCLUSIONS: Liver evaluation with MIP and ARFI contributes to a
      noninvasive prediction of cirrhosis.

PMID- 22357224
TI  - Shear wave ultrasound elastography of the prostate: initial results.
AB  - PURPOSE: This prospective study was to evaluate shear wave elastography (SWE) in
      the detection of prostate cancer (PC). METHODS: Patients scheduled for a
      transrectal ultrasound (TRUS) biopsy of the prostate because of elevated prostate
      specific antigen levels or abnormal digital rectal examination result underwent a
      standard TRUS and SWE. A second TRUS examination and sextant biopsy by a second
      physician blinded to SWE results was then performed. Pathologic result was
      reviewed, and sensitivity, specificity, negative predictive value (NPV), and
      positive predictive value (PPV) were calculated. RESULTS: A total of 53 patients
      (318 sextants) participated in the study. Mean age was 64.2 years (range, 53-79
      years). A total of 26 foci of PC were detected in 11 patients (20.7%). On the
      basis of the receiver operating characteristic curve, a value of 37 kPa was used
      as the cutoff between benign and malignant. This produced a sensitivity of 96.2%
      (25/26), a specificity of 96.2% (281/292), a PPV of 69.4% (25/36), and an NPV of
      99.6% (281/282). Six (55%) of 11 false-positive samples were secondary to benign
      calcifications. The Young modulus of PC ranged from 30 to 110 kPa (mean [SD],
      58.0 [20.7] kPa). At the patient level, if a cutoff of 40 kPa was used, all PCs
      would have been detected, and the positive biopsy rate would be 11 (50%) of 22
      compared to 11 (20.8%) of 53 without SWE--a 140% increase in the positive biopsy
      rate. CONCLUSIONS: Shear wave elastography has a high sensitivity, specificity,
      PPV, and NPV for the detection of PC. With a high PPV, patients with elevated
      prostate-specific antigen levels or abnormal results in the digital rectal
      examination and negative SWE may not require biopsy. This could significantly
      reduce the negative biopsy rate in PC detection.

PMID- 22357225
TI  - Need for intraoperative ultrasound and surgical recommendation for partial
      nephrectomy: correlation with tumor imaging features and urologist practice
      patterns.
AB  - PURPOSE: This study aimed to evaluate the need for intraoperative ultrasound
      (IOUS) and recommendation for surgical approach in the resection of renal tumors
      through a survey of practicing urologists, with correlation to tumor imaging
      features and urologist practice pattern. MATERIALS AND METHODS: An institutional
      review board-approved retrospective review, compliant with the Health Insurance
      Portability and Accountability Act, of 44 renal tumors that underwent
      laparoscopic partial nephrectomy at the study institution was performed. The
      numeric component of the RENAL nephrometry score (radius [diameter], % exophytic,
      nearness [to collecting system/renal sinus], location) was calculated for each
      case using preoperative computed tomography/magnetic resonance imaging. Five
      anonymized images of each tumor were presented to 4 academic urologists with
      varying practice patterns. Reviewers independently scored each case for its need
      for IOUS, for recommendation of a surgical technique, and for the difficulty of
      the proposed surgery. RESULTS: The RENAL scores were as follows: RENAL 1 (low
      complexity, score 4-6; n = 19); RENAL 2 (moderate complexity, score 7-9; n = 23);
      RENAL 3 (high complexity, score 10-12; n = 2). The only RENAL score component
      significantly influencing need for IOUS was percentage exophytic (P = 0.00002).
      There was an inverse relationship between normalized and averaged need for IOUS
      and percentage exophytic (P < 0.0001). The predominant influence for
      recommendation of surgical method was the reviewer him/herself, with each
      reviewer's recommendations closely matching his/her practice pattern. Size and
      percentage exophytic represented the only tumor features significantly (P = 0.03)
      influencing surgical recommendation. CONCLUSIONS: There was a significant
      difference in the perceived need for IOUS and surgical recommendation when 4
      academic urologists reviewed a series of renal masses requiring resection.
      Percentage exophytic correlated inversely with need for IOUS. Urologist's
      practice pattern and tumor size and percentage exophytic were most predictive of
      surgical recommendation.

PMID- 22357246
TI  - ACR Appropriateness Criteria (r) acute onset of scrotal pain--without trauma,
      without antecedent mass.
AB  - Men or boys, who present with acute scrotal pain without prior trauma or a known
      mass, most commonly suffer from torsion of the spermatic cord; epididymitis or
      epididymoorchitis; or torsion of the testicular appendages. Less common causes of
      pain include a strangulated hernia, segmental testicular infarction, or a
      previously undiagnosed testicular tumor. Ultrasound is the study of choice to
      distinguish these disorders; it has supplanted Tc-99 m scrotal scintigraphy for
      the diagnosis of spermatic cord torsion. MRI should be used in a problem solving
      role if the ultrasound examination is inconclusive. The ACR Appropriateness
      Criteria (r) are evidence-based guidelines for specific clinical conditions that
      are reviewed every two years by a multidisciplinary expert panel. The guideline
      development and review include an extensive analysis of current medical
      literature from peer reviewed journals and the application of a well-established
      consensus methodology (modified Delphi) to rate the appropriateness of imaging
      and treatment procedures by the panel. In those instances where evidence is
      lacking or not definitive, expert opinion may be used to recommend imaging or
      treatment.

PMID- 22357247
TI  - Acute onset of scrotal pain: without trauma, without antecedent mass.

PMID- 22357249
TI  - Addition of short-term androgen deprivation therapy to dose-escalated radiation
      therapy improves failure-free survival for select men with intermediate-risk
      prostate cancer.
AB  - BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation
      therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit
      of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa)
      is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa
      with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed
      comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS)
      with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT
      with ADT (median 6 months). On Cox proportional hazard regression that adjusted
      for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard
      ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT
      classified Gleason 4 + 3 = 7 or >=50% positive cores as unfavorable disease. The
      addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease
      (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable
      disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT
      improved FFS for men with unfavorable disease and no or mild comorbidity (P =
      0.006) but did not improve FFS for men with unfavorable disease and moderate or
      severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves
      FFS for men with unfavorable IR-PrCa, especially those with no or minimal
      comorbidity.

PMID- 22357250
TI  - Preoperative PET/CT in early-stage breast cancer.
AB  - BACKGROUND: The aim of this study was to assess the diagnostic and therapeutic
      impact of preoperative positron emission tomography and computed tomography
      (PET/CT) in the initial staging of patients with early-stage breast cancer.
      PATIENTS AND METHODS: A total of 103 consecutive patients with newly diagnosed
      operable breast cancer with tumors >=2 cm were independently examined
      preoperatively with conventional assessment (mammography, breast/axillary
      ultrasound, chest X-ray and blood samples) and PET/CT with no prior knowledge of
      the other. RESULTS: PET/CT identified a primary tumor in all but three patients
      (97%). PET/CT solely detected distant metastases (ovary, bones and lung) in 6
      patients and new primary cancers (ovary, lung) in another two patients, as well
      as 12 cases of extra-axillary lymph node involvement. In 15 patients (15%), extra
      axillary malignancy was detected by PET/CT only, leading to an upgrade of initial
      staging in 14% (14/103) and ultimately a modification of planned treatment in 8%
      (8/103) of patients. CONCLUSIONS: PET/CT is a valuable tool to provide
      information on extra-axillary lymph node involvement, distant metastases and
      other occult primary cancers. Preoperative (18)F-fluorodeoxyglucose-PET/CT has a
      substantial impact on initial staging and on clinical management in patients with
      early-stage breast cancer with tumors >=2 cm.

PMID- 22357251
TI  - Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in
      patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer.
AB  - BACKGROUND: Targeted therapy options in HER2-negative breast cancer are limited.
      This open-label, multicenter phase IB dose-escalation trial was conducted to
      determine safety, tolerability, and antitumor activity of a combination of
      docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody
      targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed
      or primary refractory advanced-stage breast cancer. PATIENTS AND METHODS:
      Patients pretreated with up to four prior chemotherapy regimens received
      increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined
      with docetaxel (100 mg/m(2) q3w). Primary end points were safety and
      tolerability. Antitumor activity was evaluated according to RECIST. Clinical
      benefit was defined as complete or partial response or stable disease for >=24
      weeks. RESULTS: Thirty-one evaluable patients were treated. Most adverse events
      were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and
      diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated
      doses of adecatumumab given in combination with docetaxel were 550 mg/m(2) q3w
      and 360 mg/m(2) qw. Clinical benefit was observed in 44% of patients treated with
      q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM
      expressing tumors. CONCLUSION: Combination therapy of adecatumumab and docetaxel
      is safe, feasible, and potentially active in heavily pretreated advanced-stage
      breast cancer.

PMID- 22357252
TI  - A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous
      radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and
      carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup
      Study.
AB  - BACKGROUND: Simultaneous adjuvant platinum-based radiochemotherapy in high-risk
      cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel
      (Taxol) and platinum followed by radiotherapy may offer further advantages
      regarding toxicity. PATIENTS AND METHODS: An open-labeled randomized phase III
      trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5)
      followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous
      radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage
      IB-IIB CC after surgery. Primary objective was progression-free survival (PFS).
      RESULTS: Overall, 271 patients were randomized and 263 were eligible for
      evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2
      year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2%
      (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival
      rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4
      toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and
      neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A.
      Early treatment termination was significantly more frequent in arm-B than in arm
      A (32.1% versus 12.9%; P = 0.001). CONCLUSIONS: Sequential chemotherapy and
      radiation in high-risk CC could not show any significant survival benefit;
      however, a different toxicity profile appeared. This sequential regime may
      constitute an alternative option when contraindications for immediate
      postoperative radiation are present.

PMID- 22357253
TI  - Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors.
AB  - BACKGROUND: Imatinib is the standard of care for patients with advanced
      gastrointestinal stromal tumors (GIST). DESIGN: This article reviews recent data
      on the impact of imatinib treatment interruption and subsequent rechallenge in
      patients with advanced GIST. RESULTS: The randomized BFR14 trial showed that (i)
      interruption of imatinib after 1, 3, or 5 years of treatment in patients with
      nonprogressive GIST was associated with a high risk of progression even in
      patients with a complete response; (ii) rechallenge with imatinib restored tumor
      control in most patients, but the tumor response seldom reached that before
      treatment interruption; (iii) patients receiving continuous imatinib had a high
      rate of prolonged tumor control, which increased with longer imatinib treatment.
      The findings in the metastatic setting have important implications regarding the
      duration of adjuvant imatinib in GIST. CONCLUSIONS: Discontinuation of imatinib
      in responding patients with advanced GIST is associated with a high risk of
      progression and is therefore not recommended. Although rechallenge is a strategy
      for treating patients who relapse after stopping imatinib, suboptimal tumor
      response indicates that continuous kinase suppression is necessary to achieve the
      best clinical outcome. Three-year adjuvant imatinib is recommended for patients
      with resected 'high-risk' GIST; however, a longer duration may provide additional
      benefits.

PMID- 22357254
TI  - Activating c-KIT mutations in a subset of thymic carcinoma and response to
      different c-KIT inhibitors.
AB  - BACKGROUND: To analyze a multi-institutional series of type C thymic carcinomas
      (TCs) (including neuroendocrine tumors), focusing on the expression and mutations
      of c-KIT. MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117,
      p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT
      exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs.
      Immunohistochemical and molecular data were statistically crossed with
      clinicopathological features. RESULTS: Overall, 29 tumors (60%) expressed CD117,
      69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers
      stained all six atypical carcinoids and five poorly-differentiated thymic
      squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT
      mutation. No mutation was detected in CD117-negative tumors and carcinoids. All
      the mutations were found in poorly-differentiated thymic squamous cell carcinomas
      expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with
      these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N,
      W557R), exon 9 (E490K) and exon 17 (D820E). CONCLUSIONS: All TCs need an
      immunohistochemical screening with CD117, while c-KIT mutation analysis is
      mandatory only in CD117-positive cases, particularly when coexpressing CD5 and
      p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can
      predict efficacy with different c-KIT inhibitors.

PMID- 22357255
TI  - Phase III study of nilotinib versus best supportive care with or without a TKI in
      patients with gastrointestinal stromal tumors resistant to or intolerant of
      imatinib and sunitinib.
AB  - BACKGROUND: This phase III open-label trial investigated the efficacy of
      nilotinib in patients with advanced gastrointestinal stromal tumors following
      prior imatinib and sunitinib failure. PATIENTS AND METHODS: Patients were
      randomized 2:1 to nilotinib 400 mg b.i.d. or best supportive care (BSC; BSC
      without tyrosine kinase inhibitor, BSC+imatinib, or BSC+sunitinib). Primary
      efficacy end point was progression-free survival (PFS) based on blinded central
      radiology review (CRR). Patients progressing on BSC could cross over to
      nilotinib. RESULTS: Two hundred and forty-eight patients enrolled. Median PFS was
      similar between arms (nilotinib 109 days, BSC 111 days; P=0.56). Local
      investigator-based intent-to-treat (ITT) analysis showed a significantly longer
      median PFS with nilotinib (119 versus 70 days; P=0.0007). A trend in longer
      median overall survival (OS) was noted with nilotinib (332 versus 280 days;
      P=0.29). Post hoc subset analyses in patients with progression and only one prior
      regimen each of imatinib and sunitinib revealed a significant difference in
      median OS of >4 months in favor of nilotinib (405 versus 280 days; P=0.02).
      Nilotinib was well tolerated. CONCLUSION: In the ITT analysis, no significant
      difference in PFS was observed between treatment arms based on CRR. In the post
      hoc subset analyses, nilotinib provided significantly longer median OS.

PMID- 22357256
TI  - Clinical correlates of 'BRCAness' in triple-negative breast cancer of patients
      receiving adjuvant chemotherapy.
AB  - BACKGROUND: We have previously reported an array comparative genomic
      hybridization profile that identifies triple-negative breast cancers (TNBC), with
      BRCA1 dysfunction and a high sensitivity to intensified dose bifunctional
      alkylating agents. To determine the effect of conventional-dose chemotherapy in
      patients with this so-called BRCA1-like profile, clinical characteristics and
      survival were studied in a large group of TNBC patients. PATIENTS AND METHODS:
      DNA was isolated and BRCA1-like status was assessed in 101 patients with early
      stage TNBC receiving adjuvant cyclophosphamide-based chemotherapy. Clinical
      characteristics and survival were compared between BRCA1-like and non-BRCA1-like
      groups. Results Sixty-six tumors (65%) had a BRCA1-like profile. Patients with
      BRCA1-like tumors tended to be younger and had more often node-negative disease
      (P = 0.06 and P = 0.03, respectively). Five-year recurrence-free survival was 80%
      for the BRCA1-like group and 75% for the non-BRCA1-like group (P = 0.35). T stage
      was the only variable significantly associated with survival. CONCLUSIONS: BRCA1
      like tumors share clinical features, like young age at diagnosis and similar
      nodal status, with breast cancers in BRCA1 mutation carriers. Their prognosis is
      similar to that of non-BRCA1-like tumors when conventional-dose chemotherapy is
      administered. TNBCs that are classified as BRCA1-like may contain a defect in
      homologous recombination and could, in theory, benefit from the addition of poly
      ADP ribose polymerase inhibitors.

PMID- 22357257
TI  - A randomised trial of primary tamoxifen versus mastectomy plus adjuvant tamoxifen
      in fit elderly women with invasive breast carcinoma of high oestrogen receptor
      content: long-term results at 20 years of follow-up.
AB  - BACKGROUND: Long-term analysis of a randomised trial in Nottingham comparing
      tamoxifen versus surgery as initial treatment demonstrated that in oestrogen
      receptor (ER)-unselected cases, surgery achieved better local control, with no
      difference in overall survival. It was suggested that for patients with ER-rich
      tumours, local control and survival may be comparable. We now present long-term
      follow-up of a randomised trial designed to address this clinical scenario.
      PATIENTS AND METHODS: One hundred and fifty three fit elderly (>=70 years) women
      with clinically node-negative primary invasive breast carcinoma <5 cm of high ER
      content [histochemical (H) score >=100] were randomised 2:1 to primary tamoxifen
      (Tam) (N = 100) or mastectomy with adjuvant tamoxifen (Mx + Tam) (N = 53).
      RESULTS: With median follow-up of 78 months, there was no statistically
      significant difference in 10-year rates of regional recurrence (9.0% versus
      7.5%), metastasis (8.0% versus 13.2%), breast cancer-specific survival (89.0%
      versus 86.8%) or overall survival (64.0% versus 66.0%) between Tam and Mx + Tam;
      however, local control was inferior with Tam (local failure rates 43.0% versus
      1.9%; P < 0.001). CONCLUSION: Irrespective of the degree of ER positivity,
      surgery achieved better local control. However, there was excellent and similar
      survival in both groups. Tam could be considered in those who are 'frail', refuse
      or prefer not to initially undergo surgery.

PMID- 22357258
TI  - Nutrition can modulate the toxicity of environmental pollutants: implications in
      risk assessment and human health.
AB  - BACKGROUND: The paradigm of human risk assessment includes many variables that
      must be viewed collectively in order to improve human health and prevent chronic
      disease. The pathology of chronic diseases is complex, however, and may be
      influenced by exposure to environmental pollutants, a sedentary lifestyle, and
      poor dietary habits. Much of the emerging evidence suggests that nutrition can
      modulate the toxicity of environmental pollutants, which may alter human risks
      associated with toxicant exposures. OBJECTIVES: In this commentary, we discuss
      the basis for recommending that nutrition be considered a critical variable in
      disease outcomes associated with exposure to environmental pollutants, thus
      establishing the importance of incorporating nutrition within the context of
      cumulative risk assessment. DISCUSSION: A convincing body of research indicates
      that nutrition is a modulator of vulnerability to environmental insults; thus, it
      is timely to consider nutrition as a vital component of human risk assessment.
      Nutrition may serve as either an agonist or an antagonist (e.g., high-fat foods
      or foods rich in antioxidants, respectively) of the health impacts associated
      with exposure to environmental pollutants. Dietary practices and food choices may
      help explain the large variability observed in human risk assessment. CONCLUSION:
      We recommend that nutrition and dietary practices be incorporated into future
      environmental research and the development of risk assessment paradigms.
      Healthful nutrition interventions might be a powerful approach to reduce disease
      risks associated with many environmental toxic insults and should be considered a
      variable within the context of cumulative risk assessment and, where appropriate,
      a potential tool for subsequent risk reduction.

PMID- 22357259
TI  - Selective upregulation of lipid metabolism in skeletal muscle of foraging
      juvenile king penguins: an integrative study.
AB  - The passage from shore to marine life of juvenile penguins represents a major
      energetic challenge to fuel intense and prolonged demands for thermoregulation
      and locomotion. Some functional changes developed at this crucial step were
      investigated by comparing pre-fledging king penguins with sea-acclimatized (SA)
      juveniles (Aptenodytes patagonicus). Transcriptomic analysis of pectoralis muscle
      biopsies revealed that most genes encoding proteins involved in lipid transport
      or catabolism were upregulated, while genes involved in carbohydrate metabolism
      were mostly downregulated in SA birds. Determination of muscle enzymatic
      activities showed no changes in enzymes involved in the glycolytic pathway, but
      increased 3-hydroxyacyl-CoA dehydrogenase, an enzyme of the beta-oxidation
      pathway. The respiratory rates of isolated muscle mitochondria were much higher
      with a substrate arising from lipid metabolism (palmitoyl-L-carnitine) in SA
      juveniles than in terrestrial controls, while no difference emerged with a
      substrate arising from carbohydrate metabolism (pyruvate). In vivo, perfusion of
      a lipid emulsion induced a fourfold larger thermogenic effect in SA than in
      control juveniles. The present integrative study shows that fuel selection
      towards lipid oxidation characterizes penguin acclimatization to marine life.
      Such acclimatization may involve thyroid hormones through their nuclear beta
      receptor and nuclear coactivators.

PMID- 22357260
TI  - How host heterogeneity governs tuberculosis reinfection?
AB  - Recurrent episodes of tuberculosis (TB) can be due to relapse of latent infection
      or exogenous reinfection, and discrimination is crucial for control planning.
      Molecular genotyping of Mycobacterium tuberculosis isolates offers concrete
      opportunities to measure the relative contribution of reinfection in recurrent
      disease. Here, a mathematical model of TB transmission is fitted to data from 14
      molecular epidemiology studies, enabling the estimation of relevant
      epidemiological parameters. Meta-analysis reveals that rates of reinfection after
      successful treatment are higher than rates of new TB, raising an important
      question about the underlying mechanism. We formulate two alternative mechanisms
      within our model framework: (i) infection increases susceptibility to reinfection
      or (ii) infection affects individuals differentially, thereby recruiting high
      risk individuals to the group at risk for reinfection. The second mechanism is
      better supported by the fittings to the data, suggesting that reinfection rates
      are inflated through a population phenomenon that occurs in the presence of
      heterogeneity in individual risk of infection. As a result, rates of reinfection
      are higher when measured at the population level even though they might be lower
      at the individual level. Finally, differential host recruitment is modulated by
      transmission intensity, being less pronounced when incidence is high.

PMID- 22357261
TI  - Elbow joint adductor moment arm as an indicator of forelimb posture in extinct
      quadrupedal tetrapods.
AB  - Forelimb posture has been a controversial aspect of reconstructing locomotor
      behaviour in extinct quadrupedal tetrapods. This is partly owing to the
      qualitative and subjective nature of typical methods, which focus on bony
      articulations that are often ambiguous and unvalidated postural indicators. Here
      we outline a new, quantitatively based forelimb posture index that is applicable
      to a majority of extant tetrapods. By determining the degree of elbow joint
      adduction/abduction mobility in several tetrapods, the carpal flexor muscles were
      determined to also play a role as elbow adductors. Such adduction may play a
      major role during the stance phase in sprawling postures. This role is different
      from those of upright/sagittal and sloth-like creeping postures, which,
      respectively, depend more on elbow extensors and flexors. Our measurements of
      elbow muscle moment arms in 318 extant tetrapod skeletons (Lissamphibia,
      Synapsida and Reptilia: 33 major clades and 263 genera) revealed that sprawling,
      sagittal and creeping tetrapods, respectively, emphasize elbow adductor, extensor
      and flexor muscles. Furthermore, scansorial and non-scansorial taxa,
      respectively, emphasize flexors and extensors. Thus, forelimb postures of extinct
      tetrapods can be qualitatively classified based on our quantitative index. Using
      this method, we find that Triceratops (Ceratopsidae), Anhanguera (Pterosauria)
      and desmostylian mammals are categorized as upright/sagittally locomoting taxa.

PMID- 22357262
TI  - Female cleaner fish cooperate more with unfamiliar males.
AB  - Joint group membership is of major importance for cooperation in humans, and
      close ties or familiarity with a partner are also thought to promote cooperation
      in other animals. Here, we present the opposite pattern: female cleaner fish,
      Labroides dimidiatus, behave more cooperatively (by feeding more against their
      preference) when paired with an unfamiliar male rather than with their social
      partner. We propose that cooperation based on asymmetric punishment causes this
      reversed pattern. Males are larger than and dominant to female partners and are
      more aggressive to unfamiliar than to familiar female partners. In response,
      females behave more cooperatively with unfamiliar male partners. Our data suggest
      that in asymmetric interactions, weaker players might behave more cooperatively
      with out-group members than with in-group members to avoid harsher punishment.

PMID- 22357263
TI  - Biting off more than you can chew: sexual selection on the free amino acid
      composition of the spermatophylax in decorated crickets.
AB  - Nuptial food gifts function to enhance male fertilization success, but their
      consumption is not always beneficial to females. In decorated crickets, the
      spermatophore transferred at mating includes a gelatinous mass, the
      spermatophylax, which is consumed by females after mating. However, females often
      discard spermatophylaxes shortly after mating, whereupon they terminate sperm
      transfer. We hypothesized that females discard gifts based on their assessment of
      the gift itself, and specifically the composition of free amino acids. We tested
      this hypothesis by comparing spermatophylaxes discarded by females after mating
      with those that were destined to be fully consumed, and employed multivariate
      selection analysis to quantify the strength and form of multivariate sexual
      selection operating on the free amino acid composition of gifts. The analysis
      yielded a saddle-shaped fitness surface with two local peaks. Different amino
      acid profiles appear to elicit continued feeding on the spermatophylax either
      because they offer the same level of gustatory appeal, or because they
      differentially affect both the gustatory appeal and texture of the
      spermatophylax. We conclude that the gustatory response of females to males'
      nuptial food gifts represents an important avenue of post-copulatory mate choice,
      imposing significant sexual selection on the free amino acid composition of the
      spermatophylax.

PMID- 22357264
TI  - Drug treatment of malaria infections can reduce levels of protection transferred
      to offspring via maternal immunity.
AB  - Maternally transferred immunity can have a fundamental effect on the ability of
      offspring to deal with infection. However, levels of antibodies in adults can
      vary both quantitatively and qualitatively between individuals and during the
      course of infection. How infection dynamics and their modification by drug
      treatment might affect the protection transferred to offspring remains poorly
      understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate
      that curing dams part way through infection prior to pregnancy can alter their
      immune response, with major consequences for offspring health and survival. In
      untreated maternal infections, maternally transferred protection suppressed
      parasitaemia and reduced pup mortality by 75 per cent compared with pups from
      naive dams. However, when dams were treated with anti-malarial drugs, pups
      received fewer maternal antibodies, parasitaemia was only marginally suppressed,
      and mortality risk was 25 per cent higher than for pups from dams with full
      infections. We observed the same qualitative patterns across three different host
      strains and two parasite genotypes. This study reveals the role that within-host
      infection dynamics play in the fitness consequences of maternally transferred
      immunity. Furthermore, it highlights a potential trade-off between the health of
      mothers and offspring suggesting that anti-parasite treatment may significantly
      affect the outcome of infection in newborns.

PMID- 22357265
TI  - High relatedness in a social amoeba: the role of kin-discriminatory segregation.
AB  - A major challenge for social theory is to explain the importance of kin
      discrimination for the evolution of altruism. One way to assess the importance of
      kin discrimination is to test its effects on increasing relatedness within
      groups. The social amoeba Dictyostelium discoideum aggregates to form a fruiting
      body composed of dead stalk and live spores. Previous studies of a natural
      population showed that where D. discoideum occurs in the soil, multiple clones
      are often found in the same small soil samples. However, actual fruiting bodies
      usually contain only one clone. We here performed experiments to gauge the effect
      of kin-discriminatory segregation on increasing relatedness. We mixed co
      occurring clones from this population using a relatedness level found in small
      soil samples. We found a lower proportion of uniclonal fruiting bodies and a
      lower level of relatedness compared with natural fruiting bodies. We found that
      the amount of relatedness increase attributable to kin-discriminatory segregation
      was small. These findings suggest a relatively minor influence of kin
      discriminatory segregation on relatedness in D. discoideum. We discuss our
      results comparing with the results of previous studies, including those of wild
      clones and laboratory mutants. We ask why wild clones of D. discoideum exhibit a
      low degree of kin-discriminatory segregation, and what alternative factors might
      account for high relatedness in D. discoideum.

PMID- 22357266
TI  - Discovery of a new family of amphibians from northeast India with ancient links
      to Africa.
AB  - The limbless, primarily soil-dwelling and tropical caecilian amphibians
      (Gymnophiona) comprise the least known order of tetrapods. On the basis of
      unprecedented extensive fieldwork, we report the discovery of a previously
      overlooked, ancient lineage and radiation of caecilians from threatened habitats
      in the underexplored states of northeast India. Molecular phylogenetic analyses
      of mitogenomic and nuclear DNA sequences, and comparative cranial anatomy
      indicate an unexpected sister-group relationship with the exclusively African
      family Herpelidae. Relaxed molecular clock analyses indicate that these lineages
      diverged in the Early Cretaceous, about 140 Ma. The discovery adds a major branch
      to the amphibian tree of life and sheds light on both the evolution and
      biogeography of caecilians and the biotic history of northeast India-an area
      generally interpreted as a gateway between biodiversity hotspots rather than a
      distinct biogeographic unit with its own ancient endemics. Because of its
      distinctive morphology, inferred age and phylogenetic relationships, we recognize
      the newly discovered caecilian radiation as a new family of modern amphibians.

PMID- 22357267
TI  - Ant workers die young and colonies collapse when fed a high-protein diet.
AB  - A key determinant of the relationship between diet and longevity is the balance
      of protein and carbohydrate in the diet. Eating excess protein relative to
      carbohydrate shortens lifespan in solitary insects. Here, we investigated the
      link between high-protein diet and longevity, both at the level of individual
      ants and colonies in black garden ants, Lasius niger. We explored how lifespan
      was affected by the dietary protein-to-carbohydrate ratio and the duration of
      exposure to a high-protein diet. We show that (i) restriction to high-protein,
      low-carbohydrate diets decreased worker lifespan by up to 10-fold; (ii) reduction
      in lifespan on such diets was mainly due to elevated intake of protein rather
      than lack of carbohydrate; and (iii) only one day of exposure to a high-protein
      diet had dire consequences for workers and the colony, reducing population size
      by more than 20 per cent.

PMID- 22357268
TI  - Generic medications for you, but brand-name medications for me.
AB  - BACKGROUND: Because generic medications are less expensive than brand-name
      medications, government and private insurers have encouraged and/or mandated the
      use of generics. OBJECTIVE: This study aimed at evaluating perceptions about
      generic medications among English-speaking women of childbearing age currently
      enrolled in U.S. TennCare (Medicaid). METHODS: We recruited a convenience sample
      of patients from the waiting room of a primary care/gynecology health clinic,
      with 80% recruitment rate among those approached. We orally administered a 25
      item questionnaire to gather sociodemographic information and to assess beliefs
      regarding the efficacy, safety, cost, and preferences for personal use of generic
      medications. RESULTS: The average age of the women (n=172) was 28.8 +/- 6.4
      years, and most were white (82.0%) and currently married (58.1%). Nearly one
      fifth (19.2%) had not completed high school. Most women believed that generic
      medications were less expensive (97.6%) and better value (60.5%) than brand-name
      medications, but only 45.3% preferred to take generics themselves. About a
      quarter (23.3%) believed that brand-name medications were more effective than
      generics, whereas 13.4% believed that generics caused more side effects. Few
      women reported that their doctor (29.7%) and/or pharmacist (35.5%) had ever
      talked to them about taking generics. CONCLUSION: Awareness of the benefits of
      generics did not equal preferences for personal use of generics among this sample
      of women enrolled in U.S. TennCare. Furthermore, women reported that providers
      both physicians and pharmacists-infrequently discussed generic substitution with
      them.

PMID- 22357269
TI  - Sex determination strategies in 2012: towards a common regulatory model?
AB  - Sex determination is a complicated process involving large-scale modifications in
      gene expression affecting virtually every tissue in the body. Although the
      evolutionary origin of sex remains controversial, there is little doubt that it
      has developed as a process of optimizing metabolic control, as well as
      developmental and reproductive functions within a given setting of limited
      resources and environmental pressure. Evidence from various model organisms
      supports the view that sex determination may occur as a result of direct
      environmental induction or genetic regulation. The first process has been well
      documented in reptiles and fish, while the second is the classic case for avian
      species and mammals. Both of the latter have developed a variety of sex
      specific/sex-related genes, which ultimately form a complete chromosome pair (sex
      chromosomes/gonosomes). Interestingly, combinations of environmental and genetic
      mechanisms have been described among different classes of animals, thus rendering
      the possibility of a unidirectional continuous evolutionary process from the one
      type of mechanism to the other unlikely. On the other hand, common elements
      appear throughout the animal kingdom, with regard to a) conserved key genes and
      b) a central role of sex steroid control as a prerequisite for ultimately normal
      sex differentiation. Studies in invertebrates also indicate a role of epigenetic
      chromatin modification, particularly with regard to alternative splicing options.
      This review summarizes current evidence from research in this hot field and
      signifies the need for further study of both normal hormonal regulators of sexual
      phenotype and patterns of environmental disruption.

PMID- 22357270
TI  - Downregulation of integrin receptor-signaling genes by Epstein-Barr virus EBNA 3C
      via promoter-proximal and -distal binding elements.
AB  - Epstein-Barr virus (EBV) establishes a persistent latent infection in B
      lymphocytes and is associated with the development of numerous human tumors.
      Epstein-Barr nuclear antigen 3C (EBNA 3C) is essential for B-cell
      immortalization, has potent cell cycle deregulation capabilities, and functions
      as a regulator of both viral- and cellular-gene expression. We performed
      transcription profiling on EBNA 3C-expressing B cells and identified several
      chemokines and members of integrin receptor-signaling pathways, including CCL3,
      CCL4, CXCL10, CXCL11, ITGA4, ITGB1, ADAM28, and ADAMDEC1, as cellular target
      genes that could be repressed by the action of EBNA 3C alone. Chemotaxis assays
      demonstrated that downregulation of CXCL10 and -11 by EBNA 3C is sufficient to
      reduce the migration of cells expressing the CXCL10 and -11 receptor CXCR3. Gene
      repression by EBNA 3C was accompanied by decreased histone H3 lysine 9/14
      acetylation and increased histone H3 lysine 27 trimethylation. In an EBV-positive
      cell line expressing all latent genes, we identified binding sites for EBNA 3C at
      ITGB1 and ITGA4 and in a distal regulatory region between ADAMDEC1 and ADAM28,
      providing the first demonstration of EBNA 3C association with cellular-gene
      control regions. Our data implicate indirect mechanisms in CXCL10 and CXCL11
      repression by EBNA 3C. In summary, we have unveiled key cellular pathways
      repressed by EBNA 3C that are likely to contribute to the ability of EBV
      immortalized cells to modulate immune responses, adhesion, and B-lymphocyte
      migration to facilitate persistence in the host.

PMID- 22357271
TI  - Human CD4+ T cell response to human herpesvirus 6.
AB  - Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent
      infection for life. HHV-6 reactivation has been associated with transplant
      rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug
      induced hypersensitivity syndrome. The poor understanding of the targets and
      outcome of the cellular immune response to HHV-6 makes it difficult to outline
      the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T
      cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell
      lines generated from healthy donors. CD4(+) T cells responding to HHV-6 in
      peripheral blood were observed at frequencies below 0.1% of total T cells but
      could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC
      and T cell cultures challenged with HHV-6 preparations indicated that gamma
      interferon (IFN-gamma) and interleukin-10 (IL-10) were appropriate markers of the
      HHV-6 cellular response. Eleven CD4(+) T cell epitopes, all but one derived from
      abundant virion components, were identified. The response was highly cross
      reactive between HHV-6A and HHV-6B variants. Seven of the CD4(+) T cell epitopes
      do not share significant homologies with other known human pathogens, including
      the closely related human viruses human herpesvirus 7 (HHV-7) and human
      cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers
      generated with these epitopes were able to detect HHV-6-specific T cell
      populations. These findings provide a window into the immune response to HHV-6
      and provide a basis for tracking HHV-6 cellular immune responses.

PMID- 22357272
TI  - Epigenetic histone modification of Epstein-Barr virus BZLF1 promoter during
      latency and reactivation in Raji cells.
AB  - The Epstein-Barr virus (EBV) predominantly establishes latent infection in B
      cells, and the reactivation of the virus from latency is dependent on the
      expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits
      only low basal activity but is activated in response to chemical or biological
      inducers, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), calcium ionophores,
      or histone deacetylase (HDAC) inhibitors. In some cell lines latently infected
      with EBV, an HDAC inhibitor alone can induce BZLF1 transcription, while the
      treatment does not enhance expression in other cell lines, such as B95-8 or Raji
      cells, suggesting unknown suppressive mechanisms besides histone deacetylation in
      those cells. Here, we found the epigenetic modification of the BZLF1 promoter in
      latent Raji cells by histone H3 lysine 27 trimethylation (H3K27me3), H3K9me2/me3,
      and H4K20me3. Levels of active markers such as histone acetylation and H3K4me3
      were low in latent cells but increased upon reactivation. Treatment with 3
      deazaneplanocin A (DZNep), an inhibitor of H3K27me3 and H4K20me3, significantly
      enhanced the BZLF1 transcription in Raji cells when in combination with an HDAC
      inhibitor, trichostatin A (TSA). The knockdown of Ezh2 or Suv420h1, histone
      methyltransferases for H3K27me3 or H4K20me3, respectively, further proved the
      suppression of Zp by the methylations. Taken together, the results indicate that
      H3K27 methylation and H4K20 methylation are involved, at least partly, in the
      maintenance of latency, and histone acetylation and H3K4 methylation correlate
      with the reactivation of the virus in Raji cells.

PMID- 22357273
TI  - Herpes simplex virus 1 VP22 regulates translocation of multiple viral and
      cellular proteins and promotes neurovirulence.
AB  - Herpes simplex virus 1 (HSV-1) protein VP22, encoded by the UL49 gene, is a major
      virion tegument protein. In the present study, we showed that VP22 was required
      for efficient redistribution of viral proteins VP16, VP26, ICP0, ICP4, and ICP27
      and of cellular protein Hsc-70 to the cytoplasm of infected cells. We found that
      two dileucine motifs in VP22, at amino acids 235 and 236 and amino acids 251 and
      252, were necessary for VP22 regulation of the proper cytoplasmic localization of
      these viral and cellular proteins. The dileucine motifs were also required for
      proper cytoplasmic localization of VP22 itself and for optimal expression of
      viral proteins VP16, VP22, ICP0, UL41, and glycoprotein B. Interestingly, a
      recombinant mutant virus with alanines substituted for the dileucines at amino
      acids 251 and 252 had a 50% lethal dose (LD(50)) for neurovirulence in mice
      following intracerebral inoculation about 10(3)-fold lower than the LD(50) of the
      repaired virus. Furthermore, the replication and spread of this mutant virus in
      the brains of mice following intracerebral inoculation were significantly
      impaired relative to those of the repaired virus. The ability of VP22 to regulate
      the localization and expression of various viral and cellular proteins, as shown
      in this study, was correlated with an increase in viral replication and
      neurovirulence in the experimental murine model. Thus, HSV-1 VP22 is a
      significant neurovirulence factor in vivo.

PMID- 22357274
TI  - Closely related archaeal Haloarcula hispanica icosahedral viruses HHIV-2 and SH1
      have nonhomologous genes encoding host recognition functions.
AB  - Studies on viral capsid architectures and coat protein folds have revealed the
      evolutionary lineages of viruses branching to all three domains of life. A
      widespread group of icosahedral tailless viruses, the PRD1-adenovirus lineage,
      was the first to be established. A double beta-barrel fold for a single major
      capsid protein is characteristic of these viruses. Similar viruses carrying genes
      coding for two major capsid proteins with a more complex structure, such as
      Thermus phage P23-77 and haloarchaeal virus SH1, have been isolated. Here, we
      studied the host range, life cycle, biochemical composition, and genomic sequence
      of a new isolate, Haloarcula hispanica icosahedral virus 2 (HHIV-2), which
      resembles SH1 despite being isolated from a different location. Comparative
      analysis of these viruses revealed that their overall architectures are very
      similar except that the genes for the receptor recognition vertex complexes are
      unrelated even though these viruses infect the same hosts.

PMID- 22357275
TI  - Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2
      and CD4 in humanized mice.
AB  - While human cells express potent antiviral proteins as part of the host defense
      repertoire, viruses have evolved their own arsenal of proteins to antagonize
      them. BST2 was identified as an inhibitory cellular protein of HIV-1 replication,
      which tethers virions to the cell surface to prevent their release. On the other
      hand, the HIV-1 accessory protein, Vpu, has the ability to downregulate and
      counteract BST2. Vpu also possesses the ability to downmodulate cellular CD4 and
      SLAMF6 molecules expressed on infected cells. However, the role of Vpu in HIV-1
      infection in vivo remains unclear. Here, using a human hematopoietic stem cell
      transplanted humanized mouse model, we demonstrate that Vpu contributes to the
      efficient spread of HIV-1 in vivo during the acute phase of infection. Although
      Vpu did not affect viral cytopathicity, target cell preference, and the level of
      viral protein expression, the amount of cell-free virions in vpu-deficient HIV-1
      infected mice was profoundly lower than that in wild-type HIV-1-infected mice. We
      provide a novel insight suggesting that Vpu concomitantly downregulates BST2 and
      CD4, but not SLAMF6, from the surface of infected cells. Furthermore, we show
      evidence suggesting that BST2 and CD4 impair the production of cell-free
      infectious virions but do not associate with the efficiency of cell-to-cell HIV-1
      transmission. Taken together, our findings suggest that Vpu downmodulates BST2
      and CD4 in infected cells and augments the initial burst of HIV-1 replication in
      vivo. This is the first report demonstrating the role of Vpu in HIV-1 infection
      in an in vivo model.

PMID- 22357276
TI  - Molecular characterization of the processing of arenavirus envelope glycoprotein
      precursors by subtilisin kexin isozyme-1/site-1 protease.
AB  - A crucial step in the life cycle of arenaviruses is the biosynthesis of the
      mature fusion-active viral envelope glycoprotein (GP) that is essential for virus
      host cell attachment and entry. The maturation of the arenavirus GP precursor
      (GPC) critically depends on proteolytic processing by the cellular proprotein
      convertase (PC) subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P). Here we
      undertook a molecular characterization of the SKI-1/S1P processing of the GPCs of
      the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the
      pathogenic Lassa virus (LASV). Previous studies showed that the GPC of LASV
      undergoes processing in the endoplasmic reticulum (ER)/cis-Golgi compartment,
      whereas the LCMV GPC is cleaved in a late Golgi compartment. Herein we confirm
      these findings and provide evidence that the SKI-1/S1P recognition site RRLL,
      present in the SKI-1/S1P prodomain and LASV GPC, but not in the LCMV GPC, is
      crucial for the processing of the LASV GPC in the ER/cis-Golgi compartment. Our
      structure-function analysis revealed that the cleavage of arenavirus GPCs, but
      not cellular substrates, critically depends on the autoprocessing of SKI-1/S1P,
      suggesting differences in the processing of cellular and viral substrates.
      Deletion mutagenesis showed that the transmembrane and intracellular domains of
      SKI-1/S1P are dispensable for arenavirus GPC processing. The expression of a
      soluble form of the protease in SKI-I/S1P-deficient cells resulted in the
      efficient processing of arenavirus GPCs and rescued productive virus infection.
      However, exogenous soluble SKI-1/S1P was unable to process LCMV and LASV GPCs
      displayed at the surface of SKI-I/S1P-deficient cells, indicating that GPC
      processing occurs in an intracellular compartment. In sum, our study reveals
      important differences in the SKI-1/S1P processing of viral and cellular
      substrates.

PMID- 22357277
TI  - Roles of E4orf6 and VA I RNA in adenovirus-mediated stimulation of human
      parvovirus B19 DNA replication and structural gene expression.
AB  - Despite its very narrow tropism for erythroid progenitor cells, human parvovirus
      B19 (B19V) has recently been shown to replicate and form infectious progeny virus
      in 293 cells in the presence of early adenoviral functions provided either by
      infection with adenovirus type 5 or by addition of the pHelper plasmid encoding
      the E2a, E4orf6, and VA RNA functions. In the present study we dissected the
      individual influence of these functions on B19V genome replication and expression
      of structural proteins VP1 and VP2. We show that, in the presence of the
      constitutively expressed E1A and E1B, E4orf6 alone is able to promote B19V DNA
      replication, resulting in a concomitant increase in VP expression levels. The
      stimulatory effects of E4orf6 require the integrity of the BC box motifs, which
      target cellular proteins such as p53 and the Mre11 DNA repair complex for
      proteosomal degradation through formation of an E3 ubiquitin ligase complex with
      E1B. VA RNA also strongly induces VP expression but, in contrast to E4orf6, in a
      replication-independent manner. This stimulation could be attributed exclusively
      to the VA I RNA transcript and does not involve major activating effects at the
      level of the B19V p6 promoter, but the nucleotide residues required for the well
      defined pathway of VA I RNA mediated stimulation of translation through
      functional inactivation of protein kinase R. These data show that the cellular
      pathways regulating B19V replication may be very similar to those governing the
      productive cycle of the helper-dependent parvoviruses, the adeno-associated
      viruses.

PMID- 22357278
TI  - Limited transferrin receptor clustering allows rapid diffusion of canine
      parvovirus into clathrin endocytic structures.
AB  - Viral pathogens usurp cell surface receptors to access clathrin endocytic
      structures, yet the mechanisms of virus incorporation into these structures
      remain incompletely understood. Here we used fluorescence microscopy to directly
      visualize the association of single canine parvovirus (CPV) capsids with cellular
      transferrin receptors (TfR) on the surfaces of live feline cells and to monitor
      how these CPV-TfR complexes access endocytic structures. We found that most
      capsids associated with fewer than five TfRs and that ~25% of TfR-bound capsids
      laterally diffused into assembling clathrin-coated pits less than 30 s after
      attachment. Capsids that did not encounter a coated pit dissociated from the cell
      surface with a half-life of ~30 s. Together, our results show how CPV exploits
      the natural mechanism of TfR endocytosis to engage the clathrin endocytic pathway
      and reveal that the low affinity of capsids for feline TfRs limits the residence
      time of capsids on the cell surface and thus the efficiency of virus
      internalization.

PMID- 22357279
TI  - Virion architecture unifies globally distributed pleolipoviruses infecting
      halophilic archaea.
AB  - Our understanding of the third domain of life, Archaea, has greatly increased
      since its establishment some 20 years ago. The increasing information on archaea
      has also brought their viruses into the limelight. Today, about 100 archaeal
      viruses are known, which is a low number compared to the numbers of characterized
      bacterial or eukaryotic viruses. Here, we have performed a comparative biological
      and structural study of seven pleomorphic viruses infecting extremely halophilic
      archaea. The pleomorphic nature of this novel virion type was established by
      sedimentation analysis and cryo-electron microscopy. These nonlytic viruses form
      virions characterized by a lipid vesicle enclosing the genome, without any
      nucleoproteins. The viral lipids are unselectively acquired from host cell
      membranes. The virions contain two to three major structural proteins, which
      either are embedded in the membrane or form spikes distributed randomly on the
      external membrane surface. Thus, the most important step during virion assembly
      is most likely the interaction of the membrane proteins with the genome. The
      interaction can be driven by single-stranded or double-stranded DNA, resulting in
      the virions having similar architectures but different genome types. Based on our
      comparative study, these viruses probably form a novel group, which we define as
      pleolipoviruses.

PMID- 22357280
TI  - High-risk human papillomavirus E5 oncoprotein displays channel-forming activity
      sensitive to small-molecule inhibitors.
AB  - High-risk human papillomavirus type 16 (HPV16) is the primary causative agent of
      cervical cancer and therefore is responsible for significant morbidity and
      mortality worldwide. Cellular transformation is mediated directly by the
      expression of viral oncogenes, the least characterized of which, E5, subverts
      cellular proliferation and immune recognition processes. Despite a growing
      catalogue of E5-specific host interactions, little is understood regarding the
      molecular basis of its function. Here we describe a novel function for HPV16 E5
      as an oligomeric channel-forming protein, placing it within the virus-encoded
      "viroporin" family. The development of a novel recombinant E5 expression system
      showed that E5 formed oligomeric assemblies of a defined luminal diameter and
      stoichiometry in membranous environments and that such channels mediated
      fluorescent dye release from liposomes. Hexameric E5 channel stoichiometry was
      suggested by native PAGE studies. In lieu of high-resolution structural
      information, established de novo molecular modeling and design methods permitted
      the development of the first specific small-molecule E5 inhibitor, capable of
      both abrogating channel activity in vitro and reducing E5-mediated effects on
      cell signaling pathways. The identification of channel activity should enhance
      the future understanding of the physiological function of E5 and could represent
      an important target for antiviral intervention.

PMID- 22357281
TI  - Genetic divergence of rotavirus nonstructural protein 4 results in distinct
      serogroup-specific viroporin activity and intracellular punctate structure
      morphologies.
AB  - Nonstructural protein 4 (NSP4) viroporin activity is critical for the replication
      and assembly of serogroup A rotavirus (RVA); however, the dramatic primary
      sequence divergence of NSP4s across serogroups raises the possibility that
      viroporin activity is not a common feature among RVs. We tested for NSP4
      viroporin activity from divergent strains, including RVA (EC and Ty-1), RVB
      (IDIR), and RVC (Cowden). Canonical viroporin motifs were identified in RVA, RVB,
      and RVC NSP4s, but the arrangement of basic residues and the amphipathic alpha
      helices was substantially different between serogroups. Using Escherichia coli
      and mammalian cell expression, we showed that each NSP4 tested had viroporin
      activity, but serogroup-specific viroporin phenotypes were identified. Only
      mammalian RVA and RVC NSP4s induced BL21-pLysS E. coli cell lysis, a classical
      viroporin activity assay. In contrast, RVA, RVB, and RVC NSP4 expression was
      universally cytotoxic to E. coli and disrupted reduction-oxidation activities, as
      measured by a new redox dye assay. In mammalian cells, RVB and RVC NSP4s were
      initially localized in the endoplasmic reticulum (ER) and trafficked into
      punctate structures that were mutually exclusive with RVA NSP4. The punctate
      structures partially localized to the ER-Golgi intermediate compartment (ERGIC)
      but primarily colocalized with punctate LC3, a marker for autophagosomes. Similar
      to RVA NSP4, expression of RVB and RVC NSP4s significantly elevated cytosolic
      calcium levels, demonstrating that despite strong primary sequence divergence, RV
      NSP4 has maintained viroporin activity across serogroups A to C. These data
      suggest that elevated cytosolic calcium is a common critical process for all
      rotavirus strains.

PMID- 22357282
TI  - Emergence of distinct brome mosaic virus recombinants is determined by the
      polarity of the inoculum RNA.
AB  - Despite overwhelming interest in the impact exerted by recombination during
      evolution of RNA viruses, the relative contribution of the polarity of inoculum
      templates remains poorly understood. Here, by agroinfiltrating Nicotiana
      benthamiana leaves, we show that brome mosaic virus (BMV) replicase is competent
      to initiate positive-strand [(+)-strand] synthesis on an ectopically expressed
      RNA3 negative strand [(-) strand] and faithfully complete the replication cycle.
      Consequently, we sought to examine the role of RNA polarity in BMV recombination
      by expressing a series of replication-defective mutants of BMV RNA3 in (+) or (-)
      polarity. Temporal analysis of progeny sequences revealed that the genetic makeup
      of the primary recombinant pool is determined by the polarity of the inoculum
      template. When the polarity of the inoculum template was (+), the recombinant
      pool that accumulated during early phases of replication was a mixture of
      nonhomologous recombinants. These are longer than the inoculum template length,
      and a nascent 3' untranslated region (UTR) of wild-type (WT) RNA1 or RNA2 was
      added to the input mutant RNA3 3' UTR due to end-to-end template switching by BMV
      replicase during (-)-strand synthesis. In contrast, when the polarity of the
      inoculum was (-), the progeny contained a pool of native-length homologous
      recombinants generated by template switching of BMV replicase with a nascent UTR
      from WT RNA1 or RNA2 during (+)-strand synthesis. Repair of a point mutation
      caused by polymerase error occurred only when the polarity of the inoculum
      template was (+). These results contribute to the explanation of the functional
      role of RNA polarity in recombination mediated by copy choice mechanisms.

PMID- 22357284
TI  - Mycobacteriophage Marvin: a new singleton phage with an unusual genome
      organization.
AB  - Mycobacteriophages represent a genetically diverse group of viruses that infect
      mycobacterial hosts. Although more than 80 genomes have been sequenced, these
      still poorly represent the likely diversity of the broader population of phages
      that can infect the host, Mycobacterium smegmatis mc(2)155. We describe here a
      newly discovered phage, Marvin, which is a singleton phage, having no previously
      identified close relatives. The 65,100-bp genome contains 107 predicted protein
      coding genes arranged in a noncanonical genomic architecture in which a subset of
      the minor tail protein genes are displaced about 20 kbp from their typical
      location, situated among nonstructural genes anticipated to be expressed early in
      lytic growth. Marvin is not temperate, and stable lysogens cannot be recovered
      from infections, although the presence of a putative xis gene suggests that
      Marvin could be a relatively recent derivative of a temperate parent. The Marvin
      genome is replete with novel genes not present in other mycobacteriophage
      genomes, and although most are of unknown function, the presence of amidoligase
      and glutamine amidotransferase genes suggests intriguing possibilities for the
      interactions of Marvin with its mycobacterial hosts.

PMID- 22357283
TI  - Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) and LMP2A function
      cooperatively to promote carcinoma development in a mouse carcinogenesis model.
AB  - The Epstein-Barr virus (EBV) proteins latent membrane proteins 1 and 2 (LMP1 and
      LMP2) are frequently expressed in EBV-associated lymphoid and epithelial cancers
      and have complex effects on cell signaling and growth. The effects of these
      proteins on epithelial cell growth were assessed in vivo using transgenic mice
      driven by the keratin 14 promoter (K14). The development of papillomas and
      carcinomas was determined in the tumor initiator and promoter model using
      dimethyl benzanthracene (DMBA), followed by repeated treatments of 12-O
      tetradecanoyl phorbol 13-acetate (TPA). In these assays, LMP1 functioned as a
      weak tumor promoter and increased papilloma formation. In contrast, mice
      expressing LMP2A did not induce or promote papilloma formation. Transgenic LMP1
      mice had slightly increased development of squamous cell carcinoma; however, the
      development of carcinoma was significantly increased in the doubly transgenic
      mice expressing both LMP1 and LMP2A. DMBA treatment induces an activating
      mutation in the Harvey-ras (H-ras(61)) oncogene, and this mutation was identified
      in most papillomas and carcinomas although several papillomas and carcinomas in
      K14-LMP1 and K14-LMP1/LMP2A mice lacked the mutation. Analysis of signaling
      pathways that are known to be activated by LMP1 and/or LMP2 indicated that all
      genotypes had high levels of activated extracellular signal-regulated kinase
      (ERK) and Stat3 in carcinomas with significantly higher activation in the doubly
      transgenic carcinomas. These findings suggest that, in combination, LMP1 and LMP2
      contribute to carcinoma progression and that this may reflect the combined
      effects of the proteins on activation of multiple signaling pathways. This study
      is the first to characterize the effects of LMP2 on tumor initiation and
      promotion and to identify an effect of the combined expression of LMP1 and LMP2
      on the increase of carcinoma development.

PMID- 22357285
TI  - Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'
      (1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H imidazo[4,5-b]pyridine] (TM-25659) in
      rat plasma by liquid chromatography-tandem mass spectrometry.
AB  - TM-25659 compound, a novel TAZ modulator, is developed for the control of bone
      loss and obesity. TAZ is known to bind to a variety of transcription factors to
      control cell differentiation and organ development. A selective and sensitive
      method was developed for the determination of TM-25659 concentrations in rat
      plasma. The drug was measured by liquid chromatography-tandem mass spectrometry
      after liquid-liquid extraction with ethyl acetate. TM-25659 and the internal
      standard imipramine were separated on a Hypersil GOLD C18 column with a mixture
      of acetonitrile-ammonium formate (10 mM) (90:10, v/v) as the mobile phase. The
      ions m/z 501.2->207.2 for TM-25659 and m/z 281.0->86.0 for imipramine in multiple
      reaction monitoring mode were used for the quantitation. The calibration range
      was 0.1-100 MUg/ml with a correlation coefficient greater than 0.99. The lower
      limit of quantitation of TM-25659 in rat plasma was 0.1 MUg/ml. The percent
      recoveries of TM-25659 and imipramine were 98.6% and 95.7% from rat plasma,
      respectively. The intra- and inter-batch precisions were 3.17-15.95% and the
      relative error was 0.38-10.82%. The developed assay was successfully applied to a
      pharmacokinetic study of TM-25659 administered intravenously (10 mg/kg) to rats.

PMID- 22357286
TI  - Optimized assays for human UDP-glucuronosyltransferase (UGT) activities: altered
      alamethicin concentration and utility to screen for UGT inhibitors.
AB  - The measurement of the effect of new chemical entities on human UDP
      glucuronosyltransferase (UGT) marker activities using in vitro experimentation
      represents an important experimental approach in drug development to guide
      clinical drug-interaction study designs or support claims that no in vivo
      interaction will occur. Selective high-performance liquid chromatography-tandem
      mass spectrometry functional assays of authentic glucuronides for five major
      hepatic UGT probe substrates were developed: beta-estradiol-3-glucuronide
      (UGT1A1), trifluoperazine-N-glucuronide (UGT1A4), 5-hydroxytryptophol-O
      glucuronide (UGT1A6), propofol-O-glucuronide (UGT1A9), and zidovudine-5'
      glucuronide (UGT2B7). High analytical sensitivity permitted characterization of
      enzyme kinetic parameters at low human liver microsomal and recombinant UGT
      protein concentration (0.025 mg/ml), which led to a new recommended optimal
      universal alamethicin activation concentration of 10 MUg/ml for microsomes.
      Alamethicin was not required for recombinant UGT incubations. Apparent enzyme
      kinetic parameters, particularly for UGT1A1 and UGT1A4, were affected by
      nonspecific binding. Unbound intrinsic clearance for UGT1A9 and UGT2B7 increased
      significantly after addition of 2% bovine serum albumin, with minimal changes for
      UGT1A1, UGT1A4, and UGT1A6. Eleven potential UGT and cytochrome P450 inhibitors
      were evaluated as UGT inhibitors, resulting in observation of nonselective UGT
      inhibition by chrysin, mefenamic acid, silibinin, tangeretin, ketoconazole,
      itraconazole, ritonavir, and verapamil. The pan-cytochrome P450 inhibitor, 1
      aminobenzotriazole, minimally inhibited UGT activities and may be useful in
      reaction phenotyping of mixed UGT and cytochrome P450 substrates. These methods
      should prove useful in the routine assessments of the potential for new drug
      candidates to elicit pharmacokinetic drug interactions via inhibition of human
      UGT activities and the identification of UGT enzyme-selective chemical
      inhibitors.

PMID- 22357287
TI  - Effect of mixing on enzymatic hydrolysis of cardboard waste: saccharification
      yield and subsequent separation of the solid residue using a pressure filter.
AB  - Cellulosic wastes, from sources such as low-quality cardboard and paper, are
      regarded as potential feedstocks for bioethanol production. One pathway from
      these cellulosic materials to ethanol is saccharification (hydrolysis) followed
      by fermentation. Saccharification is commonly performed using enzymes that are
      able to cleave the cellulosic structure to smaller units, preferably to glucose
      monomers. During the hydrolysis, mixing conditions have a considerable impact on
      the performance of the enzymes. Thus mixing conditions in the hydrolysis tank can
      also influence the downstream operations and, consequently, the overall economy
      of the bioethanol process. In this experimental study, four types of impeller, at
      different hydrolysis conditions were used. The effect of mixing on the glucose
      yield and on the filtration characteristics of the hydrolysate was evaluated. It
      was shown that not only the sugar yield depended on the mixing conditions: the
      effect on the solid-liquid separation step was even more significant.

PMID- 22357288
TI  - Comprehensive analysis of step-feeding strategy to enhance biological nitrogen
      removal in alum sludge-based tidal flow constructed wetlands.
AB  - Step-feeding strategies have been extensively studied and comprehensively
      analyzed in this study for a four-stage alum sludge-based tidal flow constructed
      wetlands (AlS-TFCWs) system. Enhanced total nitrogen removal of 83% is achieved
      under high nitrogen loading rate of 19.1 g N/m(2)d. The key issues towards the
      success of a significant nitrogen removal in step-feeding TFCWs are the bed
      resting time (which provides better aeration for nitrification) and up flow
      stage/delayed input of side stream(s) (which ensure favorable environment for
      better denitrification). Simultaneous nitrification and denitrification (SND) was
      found effective in the 1st stage of the system and SND via nitrite is the main
      nitrogen conversion mechanism. The optimal influent distribution fraction for
      step-feeding purpose can be estimated from a theoretical basis, which is a
      function of the influent BCOD/TKN ratio. Therefore the influent distribution
      fraction should be adjusted according to the variety of influent characteristics,
      rather than a fixed value.

PMID- 22357289
TI  - Pretreatment of corn stover for sugar production with switchgrass-derived black
      liquor.
AB  - To improve the cost-effectiveness of biomass-to-sugar conversion, sodium
      hydroxide (NaOH) pretreatment of switchgrass was carried out at 21 degrees C
      using previously determined optimum conditions (2% NaOH (w/v), 6h), and the spent
      alkaline liquid (black liquor) was collected and used for pretreatment of corn
      stover, a feedstock exhibiting a higher susceptibility to NaOH attack, for
      improved enzymatic hydrolysis at a reduced cost. The results showed that, because
      of the high pH and the appreciable amount of carbohydrates in the black liquor,
      sugar production during enzymatic hydrolysis of corn stover pretreated with black
      liquor was comparable to that of biomass pretreated with 1% NaOH. After black
      liquor pretreatment at the best residence time (24h), the total reducing sugar,
      glucose, and xylose yields of corn stover reached 478.5, 287.7, and 145.3mg/g raw
      biomass, respectively, indicating the viability of this novel pretreatment
      technology.

PMID- 22357290
TI  - Biodegradation kinetics and mechanism of 2,4,6-tribromophenol by Bacillus sp.
      GZT: a phenomenon of xenobiotic methylation during debromination.
AB  - A strain Bacillus sp. GZT capable of debrominating and mineralizing 2,4,6
      tribromophenol (TBP) was isolated and characterized by morphological observation,
      biochemical and physiological identification as well as 16S rRNA sequence
      analysis. Biodegradation kinetics experiments demonstrated that initial TBP
      concentration had a predominant effect on degradation efficiency. Within 120h,
      the highest TBP degradation and debromination efficiencies were up to 93.2% and
      89.3%, respectively, under the optimum condition. Ten metabolic intermediates
      including five brominated compounds, three oxidative products and two cellular
      metabolites were all identified by gas chromatography-mass spectrometer, and six
      key intermediates were doubly validated by authentic standards. The proposed
      biodegradation mechanism inferred that reductive debromination as a major
      degradation pathway could simultaneously take place at ortho- and para-positions
      on TBP, while methylated debromination was also found as a minor degradation
      pathway during this process. Within 148h degradation, nearly one-third of 3mg/L
      TBP could be completely mineralized.

PMID- 22357291
TI  - Reductive dechlorination and mineralization of pentachlorophenol in biocathode
      microbial fuel cells.
AB  - Simultaneous anaerobic and aerobic degradation pathways in two-chamber, tubular
      microbial fuel cells (MFCs) facilitated pentachlorophenol (PCP) mineralization by
      a mediator-less biocathode. PCP was degraded at a rate of 0.263 +/- 0.05 mg/L-h
      (51.5 mg/g VSS-h) along with power generation of 2.5 +/- 0.03 W/m(3). Operating
      the biocathode MFC at 50 degrees C improved the PCP degradation rate to 0.523 +/-
      0.08 mg/L-h (103 mg/g VSS-h) and power production to 5.2 +/- 0.03 W/m(3). A pH of
      6.0 increased the PCP degradation rate to 0.365 +/- 0.02 mg/L-h (71.5mg/g VSS-h),
      but reduced power. While mediators were not needed, adding anthraquinone-2,6
      disulfonate increased power and PCP degradation rates. Dominant bacteria most
      similar to the anaerobic Desulfobacterium aniline, Actinomycetes and
      Streptacidiphilus, and aerobic Rhodococcus erythropolis, Amycolatopsis and
      Gordonia were found on the biocathode. These results demonstrate efficient
      degradation of PCP in biocathode MFCs and the effects of temperature, pH and
      mediators.

PMID- 22357292
TI  - Deletion of the PHO13 gene in Saccharomyces cerevisiae improves ethanol
      production from lignocellulosic hydrolysate in the presence of acetic and formic
      acids, and furfural.
AB  - For efficient bioethanol production from lignocellulosic biomass by Saccharomyces
      cerevisiae, it is necessary to improve cellular tolerance to toxic compounds
      released during the pretreatment of biomass. The gene encoding p
      nitrophenylphosphatase, PHO13, was disrupted in a recombinant xylose-fermenting
      S. cerevisiae strain, which improved ethanol production from xylose in the
      presence of three major inhibitors, acetic and formic acids, and furfural. In
      medium supplemented with 30 mM acetic acid, the ethanol yield obtained by the
      DeltaPHO13 mutant was 0.45 g-ethanol/g-xylose. Notably, the specific ethanol
      productivity of the mutant in the presence of 90 mM furfural was fourfold higher
      than that of the control strain. The PHO13-disrupted strain produced ethanol from
      rice straw hydrolysate obtained by liquid hot-water pretreatment with a greater
      than fourfold higher xylose consumption rate than the control. Together, our
      findings demonstrate that PHO13 deletion is a simple, but effective, approach for
      improving cellulosic bioethanol production by S. cerevisiae.

PMID- 22357293
TI  - Recycling of cellulases in lignocellulosic hydrolysates using alkaline elution.
AB  - The recovery of cellulases from lignin, lignocellulosic hydrolysates and
      cellulose by alkaline washes at pH 9 and 10 was examined. The effect of the pH on
      the structural stability of purified Cel7A was analyzed by circular dichroism.
      Purified Cel7A showed conformational changes at pH 9 and 10 that were reversible
      at pH 4.8. Temperature influenced the enzymatic hydrolysis of wheat straw and may
      be critical for the efficiency of cellulase recycling from wheat straw
      hydrolysates. Operation at moderate temperatures (37 degrees C) resulted in a
      rate of saccharification 19% higher than that obtained at 50 degrees  C,
      improving cellulase recycling by 49%. Over 60% of the enzyme activity on the
      synthetic substrate 4-methylumbelliferyl-beta-d-cellobioside (MUC) may be
      recovered by using a simple alkaline wash. This is thus a promising strategy for
      enzyme recycling that is simple to implement at industrial scale, economical and
      effective.

PMID- 22357294
TI  - Biomaterial film for soluble organic sorption and anti-microbial activity in
      water environment.
AB  - A cost competitive biomaterial for widespread applications in food and water
      technology is an urgent need. We report a new hydrophobic biomaterial film for
      soluble pollutant sorption and reduction of microbial load in water environment.
      Guar gum from the seeds of Cyamopsis tetragonolobus was hydrophobically modified
      following benzoyl chloride reaction in aqueous alkali. The new biopolymer
      derivative is insoluble in water and form castable films with a high degree of
      surface hydrophobicity. The film water vapor permeability was 0.233+/
      0.029gmmkPa(-1)h(-1)m(-2) and the tensile property was 38.65+/-3.66MPa. The film
      surface contact angle against water was 77.36+/-1.09 degrees . The new
      biomaterial film demonstrated strong antimicrobial contact killing against both
      gram positive and gram negative bacteria. It also act as an efficient sorbent for
      a range of water soluble organic pollutants.

PMID- 22357295
TI  - Effect of biostimulation on community level physiological profiles of
      microorganisms in field-scale biopiles composed of aged oil sludge.
AB  - Four biopiles were constructed for the bioremediation of total petroleum
      hydrocarbons (TPHs) in aged oily sludge by indigenous microorganisms. Three
      biopiles were treated with bulking agent, nutrients or their combination with the
      fourth pile serving as the control. Responses of microbial community level
      physiological profiles (CLPPs) to these biostimulation strategies were estimated,
      and variances among three layers within each biopile were evaluated. Microbial
      metabolic activity and diversity and the numbers of two species of bacteria were
      significantly enhanced by the addition of bulking agent, which also made the
      layers more homogeneous. In contrast, the application of large amounts of
      nutrients had a suppressing effect on the microbes. After 220 days, 49.62% of
      TPHs were removed from the middle layer of the bulking agent pile, whereas only
      20.44% were removed from the inner layer of the control. This study aims to
      provide experience to improve the remediation efficiency of future
      investigations.

PMID- 22357297
TI  - The difficulties of enhancing public understanding of the social determinants of
      health in the United States: a commentary on Pesce, Kpaduwa, Danis (2011).

PMID- 22357298
TI  - Effect of unequal employment status on workers' health: results from a Japanese
      national survey.
AB  - This study assesses the possibility of a period effect on Japanese workers'
      health and its association with historical changes in the work environment. We
      used multi-year national cross-sectional surveys, the Comprehensive Survey of
      Living Conditions for 2001, 2004, and 2007, and estimated the period effect on
      the health of employed workers aged 18-65 years. The prevalence of ill-health
      indicators (poor self-rated health status, subjective symptoms, and the number of
      respondents receiving consultations from medical doctors and other health
      professionals) significantly increased during this period. Deteriorating trends
      in these health indicators persisted after adjusting for age and cohort effects
      and for individual factors such as employment, marital, and child-rearing status.
      Furthermore, after adjusting for income level as an individual factor,
      deteriorating trends remained for the poor self-rated health status of male
      employees, subjective symptoms of female employees, and receiving medical
      consultations for both genders. The health status of employed workers in Japan
      deteriorated, especially from 2004 to 2007, regardless of age and cohort effects.
      After taking individual socio-economic factors and the effects of the recession
      on society into consideration, we hypothesized a posteriori that the increase in
      precarious non-regular work may be the main factor underlying this period effect
      and may be the cause of the deterioration in workers' health.

PMID- 22357299
TI  - Comparing self-rated health and self-assessed change in health in a longitudinal
      survey: which is more valid?
AB  - Self-rated health (SRH) is commonly used in longitudinal analyses as a repeated
      outcome measure. This assumes that computed changes in SRH over time truly
      represent within-individual changes in underlying health. The longitudinal
      validity of SRH, however, is threatened by ceiling effects (where people
      reporting the highest level of SRH cannot report subsequent improved health),
      insensitivity to small changes within SRH categories, reference group effects
      (where individuals assess their health changes relative to their peers) and
      stability in SRH even when change in underlying health is occurring. We assessed
      the longitudinal validity of SRH by comparing computed changes in SRH with a
      measure of self-assessed change in health (SACH). We used two waves of data (2003
      2005) from the New Zealand longitudinal Survey of Family, Income and Employment
      (SoFIE). Computed change in SRH and SACH were compared directly and also in
      regression models using an objective measure of health outcome change
      (hospitalisations within the past year). Computed change in SRH and SACH were not
      well correlated, consistent with ceiling and/or categorisation effects in SRH. In
      regression models, SACH was more strongly predictive of hospitalisation than
      computed change in SRH (worse SACH was associated with an increased odds of
      hospitalisation of 3.7 compared to 1.8 for decreased computed change in SRH).
      SACH may be affected by recall bias, but if SRH is used as a repeated outcome
      measure in longitudinal analyses, results may also be biased, if change in SRH
      does not occur in response to significant health events.

PMID- 22357300
TI  - Disciplined doctors: the electronic medical record and physicians' changing
      relationship to medical knowledge.
AB  - This study explores the effects of the electronic medical record (EMR) on the
      power of the medical profession. It is based on twenty-five in-depth interviews
      with administrators and physicians across three departments of a large, U.S.
      integrated health system, as well as ethnographic observation, all of which took
      place between September of 2009 and December of 2010. While scholarship on
      professional power has tended toward the opposite poles of professional dominance
      and deprofessionalization or proletarianization, I find that doctors'
      interactions with the EMR reconcile these perspectives by making physicians'
      professional identities consistent with their subordination to bureaucratic
      authority. After examining the electronic medical record as a disciplinary
      technology, the paper analyzes variation in the extent to which practitioners'
      professional identities are reconciled with bureaucratic subordination across the
      different departments studies.

PMID- 22357301
TI  - The ambivalence of stigma and the double-edged sword of HIV/AIDS intervention in
      Burkina Faso.
AB  - This article analyses the causes of HIV stigmatisation in Burkina Faso as
      perceived by people living with HIV/AIDS (PLHIV) and people working in AIDS
      related Community Based Organisations (CBOs). Stigmatisation continues to be a
      pressing issue when dealing with HIV/AIDS in Sub-Saharan Africa. The article is
      based on direct observation of HIV-related practices within 20 CBOs in Burkina
      Faso, as well as semi-structured interviews or focus group discussions with 72
      PLHIV and 90 professionals and volunteers working in CBOs. PLHIV were chosen by
      convenience sampling among the persons who accessed CBO services and were
      interviewed about their life quality and experience relating to HIV.
      Professionals and volunteers were interviewed about their strategies, their
      achievements, and the problems they encountered. The research was conducted in
      the course of three months fieldwork between September and November 2009. Our
      principal findings show, firstly, that moral or social stigmatisation does not in
      any simple way derive from fear, ignorance or inaccurate beliefs but that it is
      also established and continually reinforced by official campaigns addressing
      HIV/AIDS. Secondly, we show that stigmatisation is a socially complex and
      ambiguous process. Based on these empirical findings we conclude that HIV/AIDS
      need no longer be approached in AIDS intervention as a sexually acquired and
      fatal disease. When reliable access to antiretroviral drugs is in place, AIDS
      becomes a chronic condition with which one can live for many years, and this
      makes it easier to address HIV and moral or social stigmatisation by downplaying
      the current focus upon sexuality and morality.

PMID- 22357302
TI  - Marked effects of Pilates on the abdominal muscles: a longitudinal magnetic
      resonance imaging study.
AB  - PURPOSE: The study's purpose was to analyze the effects of Pilates on the volume
      of the rectus abdominis (RA), obliques, and transversus abdominis, with the last
      two considered conjointly (OT). METHODS: The volume of OT and RA were determined
      using magnetic resonance imaging in nine nonactive healthy women, before and
      after 36 wk of a standardized Pilates training program (Modern Pilates). RESULTS:
      The volume of the dominant OT was increased by 8% (P < 0.05) with training,
      whereas the nondominant OT volume remained unchanged (+2%, P = 0.58). The total
      volume of RA increased by 21% after Pilates (P < 0.05) because of a similar
      increase of dominant and nondominant RA volume (21% and 20%, respectively, P <
      0.05). Before Pilates, the volume of the OT was 8% greater in the nondominant
      compared with the dominant side (P < 0.01). This asymmetry was compensated by
      Pilates training (2%, P = 0.43). No side-to-side asymmetries in RA muscle volumes
      were observed either before (2%, P = 0.51) or after (1%, P = 0.81) Pilates.
      CONCLUSIONS: The present study reveals the existence of asymmetries in the
      muscles of the abdominal wall in nonactive healthy women. Pilates practice twice
      a week for 9 months elicits hypertrophy of the abdominal wall muscles,
      particularly of the RA, and eliminates preexisting asymmetries of the OT. Modern
      Pilates can be recommended as an effective method to reinforce the muscles of the
      abdominal wall and to compensate preexisting asymmetric developments.

PMID- 22357303
TI  - Nutritional strategies to prevent hypoglycemia at exercise in diabetic
      adolescents.
AB  - Studies on nutritional strategies to prevent exercise-induced hypoglycemia in
      adolescents with type 1 diabetes are scarce. OBJECTIVE: This study aimed to
      compare the effect of two food strategies on blood glucose (BG) during and after
      60 min of moderate-intensity exercise. METHODS: Subjects performed exercise 120
      min after breakfast in three conditions: 1) standardized breakfast + preexercise
      placebo beverage (PL), 2) standardized breakfast + preexercise CHO beverage (8 mg
      of CHO.kg of body weight.min of exercise; CHO), or 3) protein-supplemented
      breakfast (8 mg of protein.kg of body weight.min of exercise added to the
      standardized breakfast) + preexercise placebo beverage (PROT). As soon as BG
      falls <4 mmol.L or symptomatic hypoglycemia occurred during exercise, the session
      was stopped and CHO tablets were provided to correct hypoglycemia. RESULTS: Ten
      subjects (age = 14.0 +/- 1.5 yr) participated in all conditions. BG decreased by
      6.0 +/- 1.9, 1.0 +/- 3.1, and 4.6 +/- 1.9 mmol.L in PL, CHO, and PROT conditions,
      respectively (P < 0.05). The proportion of subjects reaching hypoglycemic values
      or sensations of hypoglycemia was significantly different between conditions with
      4/10, 1/10, and 0/10 in the PL, CHO, and PROT conditions (P < 0.05). CONCLUSIONS:
      The preexercise CHO beverage induced the least dramatic BG decrease during
      exercise. The PROT breakfast induced an overall similar BG drop compared to PL, a
      larger BG drop compared to CHO, but a similar rate of hypoglycemia compared to
      CHO. Our results suggest that taking CHO supplement before unplanned exercise is
      still the best strategy to prevent exercise-induced hypoglycemia in an adolescent
      population. However, a protein supplement strategy may also have some benefits in
      limiting the rate of hypoglycemia during and immediately after exercise.

PMID- 22357304
TI  - [A woman with fever and a painful hip and lower back].
AB  - A 66-year-old woman presented with fever and acute pain in her lower back and
      left hip. She used prednison for arteritis temporalis. Abdominal radiography
      revealed no signs of free intraperitoneal gas, but instead a radiolucent area
      below the spleen suggesting free retroperitoneal gas. This was confirmed by CT
      scan of the abdomen and surgery, when a diverticulitis of the colon descendens
      with retroperitoneal perforation was diagnosed.

PMID- 22357305
TI  - [A young man with parasites during surgery].
AB  - An 18-year-old man came to the Emergency Room at the Academic Hospital Paramaribo
      (Suriname) with a solitary supra-umbilical gunshot-wound. The patient was
      hypovolemic, with dropping blood pressure and rising pulse, surgery was
      indicated. After incision of the abdominal midline 1.5 l of blood drained,
      immediately followed by the appearance of 2 long thin worms. During inspection of
      the abdominal cavity a perforation of the duodenum and sigmoid and a mesenterial
      bleeding was seen and treated. Inspection of the small intestine showed presence
      of Ascaris lumbricoides (roundworm).

PMID- 22357306
TI  - ['Vascular depression': a valid diagnosis?].
AB  - The diagnosis 'vascular depression' was reintroduced to old-age psychiatry about
      10 years ago. The introduction of advanced imaging techniques has made it
      possible to link mood symptoms to vascular brain damage. In patients suffering
      from depression in which cerebrovascular damage plays an important role,
      different forms of diagnostics and treatment may be necessary. The symptom
      profiles of various depressive disorders do not differ widely, which makes it
      difficult to diagnose 'vascular depression' in daily practice. Thus, it does not
      meet the criteria of a distinct disease entity. However, the prognosis of
      patients with vascular depression is different and these patients respond less
      well to the usual therapy. Therefore, it is important to develop new treatment
      strategies for this patient group. The method of staging and profiling of
      depression in the elderly can be useful in this.

PMID- 22357307
TI  - [Non-motor symptoms of Parkinson's disease].
AB  - Parkinson's disease has traditionally been viewed as a disease with only motor
      features. Nowadays, a wide variety of non-motor symptoms and signs are also
      recognised as being characteristic of the disease. Non-motor symptoms, most
      importantly autonomic dysfunction, neuropsychiatric symptoms and sleep problems,
      are prevalent in virtually all Parkinson's disease patients and influence the
      quality of life more than the motor symptoms. Patients may visit a variety of
      health care professionals, but non-motor symptoms are often missed, because
      physicians do not explicitly ask patients about them or do not recognise them as
      being part of the disease. Knowledge of non-motor symptoms is important to avoid
      unnecessary additional testing. Specific treatment options are available, as
      described in the Dutch multidisciplinary guidelines on Parkinson's disease.

PMID- 22357310
TI  - [Sick leave and the general practitioner].
AB  - General practitioners and occupational physicians both deal with patients on sick
      leave. Sometimes they give conflicting advice and there is too little
      collaboration. Collaboration is necessary to improve care for sick workers. A
      collective training route and more focus on sick leave in guidelines for general
      practitioners, such as the guidelines from the Dutch College of General
      Practitioners, may be of help in this respect. Also, more insight into
      interdoctor variation is needed.

PMID- 22357311
TI  - [Research in palliative care; is something better than nothing?].
AB  - How strictly should we apply the rules of good clinical research, when the
      research in question is performed with terminally ill patients? Recently, a
      retrospective study into the effectiveness of radiotherapy for sialorrhoea in
      patients with a degenerative disease, such as amyotrophic lateral sclerosis, was
      published in the Nederlands Tijdschrift voor Geneeskunde(Dutch Journal of
      Medicine). This commentary defends the position that in palliative care sometimes
      having weak scientific evidence is better than having nothing. Here, the need of
      the patient and the intention of the physician are 2 ethically relevant issues
      that need to be taken into account. If there is at least some evidence to believe
      an intervention is beneficial for the patient, this is a strong reason to provide
      it. And if such intervention can only be studied in a methodologically suboptimal
      way, then it is better to have that information, albeit not perfect, than none at
      all. This is not a justification of weak studies as such. If possible, palliative
      care should be as evidence-based as all other types of medical care. However,
      when the circumstances make methodologically perfect research impossible, it is
      better to act on weak evidence than on none at all.

PMID- 22357312
TI  - [Occupational physician: doctor without care for patients?].
AB  - In the Netherlands there is a lack of collaboration between occupational and
      treating physicians. This is due to legislation dating from a century ago
      determining that treating physicians are not allowed to advise about work
      capacity and return-to-work and that occupational physicians are not allowed to
      treat patients. Recently the Dutch Health Council urged improvement of the
      collaboration for the sake of the health and work participation of patients.
      There is much scientific evidence that work is good for health and prevents
      social exclusion. An example of integrated occupational and curative care is
      presented: care delivered by a multidisciplinary team including an occupational
      physician demonstrated that patients with work disability due to chronic back
      pain returned to work 4 months earlier in a sustainable way and that they also
      functioned better in their private life. Integrated care is also important for
      society: there is a return on investment of ? 26 for every euro. The author
      pleads that occupational health care should be brought into mainstream health
      care with a work participation as a shared treatment goal.

PMID- 22357314
TI  - Clinical ethics support services: an evolving model.
AB  - Ethical issues arising in clinical practice are complex and clinicians must be
      able to manage the needs of ethically vulnerable patients and families. This
      paper describes a model for providing Clinical Ethics Support Services as a broad
      spectrum of care for management of conflict and ethically difficult situations in
      health care and describes how an ethics consultation process was transformed to a
      Holistic Care Continuum for managing the needs of ethically vulnerable patients.
      During a 4-year journey at a regional medical center, a Family Support Team
      played a central role in identification of ethically vulnerable patients/family,
      interdisciplinary connectivity, and iterative engagement in the clinical milieu.
      Concepts of professional advocacy and interdisciplinary perspectives resulted in
      a model for ethically sound patient care promoting communication among
      patients/family, staff, and professionals; clarification of interdisciplinary
      roles and responsibilities; establishment of mutually derived goals and shared
      solutions; and implementation of interventions maximizing institutional
      resources.

PMID- 22357313
TI  - Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic
      mimicry formation of tumors to accelerate metastasis.
AB  - BACKGROUND: Antiangiogenic therapy is one of the most significant advances in
      anticancer treatment. The benefits of antiangiogenic therapies of late-stage
      cancers have been investigated but are still too limited. METHODS: We used an
      ovarian cancer model to test the effect of short-term bevacizumab treatment on
      metastasis as measured by bioluminescence. Western blotting and CD34-PAS dual
      staining were performed to assess hypoxia-inducible transcription factor-1alpha
      (HIF-1alpha) expression and vasculogenic mimicry(VM) formation. Cell viability
      was examined by a CCK8 assay. RESULTS: Bevacizumab demonstrated antitumor effects
      in models of ovarian cancer, but also accelerated metastasis together, with
      marked hypoxia and VM formation in mice receiving short-term therapy. Bevacizumab
      treatment did not affect SKOV3 cell viability and the amount of VM in three
      dimensional culture. CONCLUSION: These results suggest that antiangiogenic
      therapy may potentially influence the progression of metastatic disease, which
      has been linked to the hypoxic response and VM formation.

PMID- 22357315
TI  - Evaluating health literacy in people with mental illness using the Test of
      Functional Health Literacy in Adults.
AB  - BACKGROUND: Health literacy is understudied in the mentally ill population, yet
      it is clear that a high level of health literacy is essential for successful
      management of illnesses such as schizophrenia and depression. To investigate
      health literacy in people with mental illness living in urban Australia, and to
      evaluate the relationships between medication adherence and health literacy.
      METHOD: Thirty people with schizophrenia and 30 with major depression were
      assessed with Test of Functional Health Literacy in Adults (TOFHLA). DISCUSSION:
      The level of health literacy in our mentally ill participants was comparable with
      that of the general Australian public, and considerably higher than the rates of
      health literacy reported in US studies. There appear to be national differences
      in health literacy, which limit comparison between studies undertaken in
      different countries. There was no association between health literacy and
      medication compliance. Our results suggest that poor health literacy does not
      explain medication nonadherence in people with schizophrenia or depression living
      in Australia.

PMID- 22357316
TI  - A comparative study of nozzle/diffuser micropumps with novel valves.
AB  - This study conducts an experimental study concerning the improvement of
      nozzle/diffuser micropump design using some novel no-moving-part valves. A total
      of three micropumps, including two enhancement structures having two-fin or
      obstacle structure and one conventional micro nozzle/diffuser design, are made
      and tested in this study. It is found that dramatic increase of the pressure
      drops across the designed micro nozzles/diffusers are seen when the obstacle or
      fin structure is added. The resultant maximum flow rates are 47.07 mm3/s and
      53.39 mm3/s, respectively, for the conventional micro nozzle/diffuser and the
      added two-fin structure in micro nozzle/diffuser operated at a frequency of 400
      Hz. Yet the mass flow rate for two-fin design surpasses that of conventional one
      when the frequency is below 425 Hz but the trend is reversed with a further
      increase of frequency. This is because the maximum efficiency ratio improvement
      for added two-fin is appreciably higher than the other design at a lower
      operating frequency. In the meantime, despite the efficiency ratio of the
      obstacle structure also reveals a similar trend as that of two-fin design, its
      significant pressure drop (flow resistance) had offset its superiority at low
      operating frequency, thereby leading to a lesser flow rate throughout the test
      range.

PMID- 22357317
TI  - Mechanisms of suppression and enhancement of photocurrent/conversion efficiency
      in dye-sensitized solar-cells using carotenoid and chlorophyll derivatives as
      sensitizers.
AB  - The mechanisms of suppression and enhancement of photocurrent/conversion
      efficiency (performance) in dye-sensitized solar cells, using carotenoid and
      chlorophyll derivatives as sensitizers, were compared systematically. The key
      factor to enhance the performance was found to be how to minimize interaction
      among the excited-state dye-sensitizer(s). In a set of retinoic-acid (RA) and
      carotenoic-acid (CA) sensitizers, having n conjugated double bonds, CA7 gave rise
      to the highest performance, which was reduced toward RA5 and CA13. The former was
      ascribed to the generation of triplet and the resultant singlet-triplet
      annihilation reaction, while the latter, to the intrinsic electron injection
      efficiency. In a set of shorter polyene sensitizers having different
      polarizabilities, the one with the highest polarizability (the highest trend of
      aggregate formation) exhibited the higher performance toward the lower dye
      concentration and the lower light intensity, contrary to our expectation. This is
      ascribed to a decrease in the singlet-triplet annihilation reaction. The
      performance of cosensitization, by a pair of pheophorbide sensitizers without and
      with the central metal, Mg or Zn, was enhanced by the light absorption
      (complementary rather than competitive), the transition-dipole moments
      (orthogonal rather than parallel) and by the pathways of electron injection
      (energetically independent rather than interactive).

PMID- 22357318
TI  - Benefits of combinations of vitamin A, C and E derivatives in the stability of
      cosmetic formulations.
AB  - Chemically stable ester derivatives of vitamins A, C and E have become a focus of
      interest for their role in the satisfactory results in skin aging treatments.
      Accordingly, the aim of this study was to evaluate the physical and chemical
      stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl
      tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies
      of physical stability, a Brookfield rheometer was used to determine rheological
      behavior of formulations containing the vitamins. Chemical stability was
      determined by HPLC on a Shimadzu system with UV detection. Results showed that
      formulations had pseudoplastic behavior and that vitamins did not alter their
      apparent viscosity and thixotropy. In the chemical stability studies, first-order
      reaction equations were used for determinations of the shelf-life of vitamins
      derivatives considering a remaining concentration of 85%. Combined vitamins in a
      single formulation had a slightly lower degradation rate as compared to different
      preparations containing only one of the vitamins. Considering that many cosmetic
      formulations contain vitamin combinations it is suggested that the present study
      may contribute to the development of more stable formulations containing
      liposoluble vitamins.

PMID- 22357319
TI  - Preparation and physical properties of chitosan benzoic acid derivatives using a
      phosphoryl mixed anhydride system.
AB  - Direct benzoylation of the two hydroxyl groups on chitosan was achieved using a
      phosphoryl mixed anhydride system, derived from trifluoroacetic anhydride (TFAA),
      benzoic acids (BAs), and phosphoric acid (PA). The reaction is operated as a one
      pot process under mild conditions that does not require neither an inert
      atmosphere nor dry solvents. The structures of the synthesized compounds were
      confirmed by NMR and IR spectroscopy. Solubility tests on the products revealed
      that they were soluble in organic solvents such as N,N-dimethylformamide (DMF),
      dimethylsulfoxide (DMSO), and acetone. In the meantime, a morphological study by
      scanning electron microscopy (SEM) evidently indicated that the chitosan
      benzoates underwent significant structural changes after the benzoylation.

PMID- 22357320
TI  - 2,3,5,4'- tetrahydroxystilbene-2-O-beta-D-glycoside biosynthesis by suspension
      cells cultures of Polygonum multiflorum Thunb and production enhancement by
      methyl jasmonate and salicylic acid.
AB  - Friable calli of Polygonum multiflorum Thunb have been induced in MS medium
      supplemented with 6-benzylaminopurine (6-BA) and kinetin (KT). Suspension
      cultures were initiated from friable calli by inoculating calli in liquid MS
      medium in shake flasks in the dark and 25  degrees C on an orbital shaker at 100
      rpm. The maximum dry weight (DW, 7.85 g/L) and 2,3,5,4'-tetrahydroxystilbene-2-O
      beta-D-glycoside (THSG, 56.39 mg/L) of suspension cells was obtained in MS medium
      after 16 days culture. Both methyl jasmonate (MeJA) and salicylic acid (SA) could
      increase THSG production. The most appropriate concentration of MeJA was 100
      MUmol/L in MS medium, in which concentration THSG content reached the maximum
      value of 147.79 mg/L, which represented a 162.36% increase compared to that of
      the control (56.33 mg/L). The most appropriate concentration of SA was 125
      MUmol/L in MS medium, at which concentration THSG content reached its maximum
      value of 116.43 mg/L, a 106.69% increase compared to that of the control (56.33
      mg/L).

PMID- 22357321
TI  - Synthesis and biological evaluation of 2-(3-fluoro-4-nitro phenoxy)-n
      phenylacetamide derivatives as novel potential affordable antitubercular agents.
AB  - A novel series of 2-(3-fluoro-4-nitrophenoxy)-N-phenylacetamide compounds were
      designed, synthesized and in vitro assessed for their antitubercular activities
      by a microdilution method. All the novel derivatives exerted potent or moderate
      active against M. tuberculosis H37Rv, with MIC values ranging from 4 to 64
      MUg/mL. The most potent derivative 3m showed an identical MIC value of 4 MUg/mL
      for both M. tuberculosis H37Rv and rifampin-resistant M. tuberculosis 261. It
      demonstrated no inhibitory effects against six different tumor cell lines by a
      MTT assay and had a good safety profile in a vero cell line, providing a good
      lead for subsequent optimization in search of novel affordable antitubercular
      agents.

PMID- 22357322
TI  - Structure-odor relationships of alpha-santalol derivatives with modified side
      chains.
AB  - (Z)-alpha-Santalol, which has a unique woody odor, is a main constituent of
      sandalwood essential oil. We investigated the structure-odor relationship of (Z)
      alpha-santalol and its derivatives, focusing on the relationship between the
      structure of the side chain and the odor of the compounds. Various alpha-santalol
      derivatives (aldehydes, formates, and acetates) were synthesized from (Z)- and
      (E)-alpha-santalol, which were prepared from (+)-3-bromocamphor through
      modifications of a reported synthetic route. The Z- and E-isomers of alpha
      santalols have different double-bond configurations in the side chain. Analogues
      with saturated side chains were also prepared from the corresponding alpha
      santalols, and the odors of the all the prepared compounds were evaluated. We
      found that the odors of the Z-isomers (woody) were similar to those of the
      corresponding saturated compounds, but clearly different from the odors of the
      corresponding E-isomers (odorless, fresh, or fatty). These results indicate that
      the relative configuration of the side chain with respect to the santalane frame
      plays an important role in the odor of alpha-santalol. E-configuration in the
      side chain eliminates the woody odor character of alpha-santalol and its examined
      derivatives, whereas the Z-configuration or saturation of the carbon side chain
      does not.

PMID- 22357323
TI  - Evidence for multiple routes in learning to read.
AB  - We describe a multiple-route model of reading development in which coarse-grained
      orthographic processing plays a key role in optimizing access to semantics via
      whole-word orthographic representations. This forms part of the direct
      orthographic route that gradually replaces phonological recoding during the
      initial phases of reading acquisition. The model predicts distinct developmental
      trajectories for pseudo-homophone and transposed-letter effects - two benchmark
      phenomena associated with phonological recoding and coarse-grained orthographic
      processing, respectively. Pseudo-homophone effects should decrease over the first
      years of reading acquisition, whereas transposed-letter effects should initially
      increase. These predictions were tested in a lexical decision task with 334
      children in grades 1-5, and 29 skilled adult readers. In line with the
      predictions, we found that the pseudo-homophone effect diminished as reading
      level increased, whereas the transposed-letter effect first increased and then
      diminished.

PMID- 22357324
TI  - Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells:
      an implicative role of SIRT1 in the ovary.
AB  - BACKGROUND: Resveratrol is a natural polyphenolic compound known for its
      beneficial effects on energy homeostasis, and it also has multiple properties,
      including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently,
      silent information regulator genes (Sirtuins) have been identified as targets of
      resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone
      deacetylase, is a principal modulator of pathways downstream of calorie
      restriction, and the activation of SIRT1 ameliorates glucose homeostasis and
      insulin sensitivity. To date, the presence and physiological role of SIRT1 in the
      ovary are not known. Here we found that SIRT1 was localized in granulosa cells of
      the human ovary. METHODS: The physiological roles of resveratrol and SIRT1 in the
      ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1
      expression. SIRT1 protein expression of cultured cells and luteinized human
      granulosa cells was investigated by Western blot. Rat granulosa cells were
      obtained from diethylstilbestrol treated rats. The cells were treated with
      increasing doses of resveratrol, and subsequently harvested to determine mRNA
      levels and protein levels. Cell viability was tested by MTS assay. Cellular
      apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining.
      RESULTS: SIRT1 protein was expressed in the human ovarian tissues and human
      luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent
      concentration-dependent inhibition of rat granulosa cells viability. However,
      resveratrol-induced inhibition of rat granulosa cells viability is independent of
      apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR,
      and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western
      blot analysis was consistent with the results of quantitative real-time RT-PCR
      assay. In addition, progesterone secretion was induced by the treatment of
      resveratrol. CONCLUSIONS: These results suggest a novel mechanism that
      resveratrol could enhance progesterone secretion and expression of luteinization
      related genes in the ovary, and thus provide important implications to understand
      the mechanism of luteal phase deficiency.

PMID- 22357325
TI  - Thumb strength in all types of triphalangeal thumb.
AB  - Strength is regarded as normal in patients with an opposable triphalangeal thumb.
      Our clinical impression is, however, that intrinsic musculature is probably
      affected in all forms of triphalangeal thumb. Therefore, we established the
      strength of 38 thumbs in patients with a triphalangeal thumb. Patients were
      excluded if the intrinsic musculature was enhanced or if osteotomies of the first
      metacarpal were performed. On average, strength of all thumb functions was
      significantly diminished, up to 63% for opposition strength. Strength of the
      power grip was on average 70%. As shown in this study, strength of the
      musculature of the thumb is affected in all types of triphalangeal thumb.
      Although strength of the thumb is diminished, in the investigated group it is
      apparently sufficient in daily life, as these individuals did not seek surgical
      enhancement. However, reconstructive procedures that enhance intrinsic
      musculature must be considered in all types of triphalangeal thumb.

PMID- 22357326
TI  - The prevalence of pseudoepiphyses in the metacarpals of the growing hand.
AB  - Normally the metacarpals have an epiphysis at one end--distally for the second to
      fifth and proximally for the first. Pseudoepiphyses are notches or clefts that
      occur at the non-epiphyseal ends of bones where an epiphyseal plate would be
      expected and are common incidental findings in the metacarpals of the growing
      hand. We aimed to identify the prevalence of pseudoepiphyses on serial
      radiographs of 610 healthy asymptomatic children. Pseudoepiphyses in the form of
      notches or clefts were common, identified most often in the second metacarpal
      (15.25%), fifth metacarpal (7.21%), and third metacarpal (0.49%). Complete
      pseudoepiphyses, in which the cleft extended across the full width of the
      metacarpal, were seen in the first metacarpal (1.97%) and the second metacarpal
      (1.31%). Pseudoepiphyses are a normal variant of metacarpal ossification and
      should not be confused with fractures in skeletally immature patients.

PMID- 22357327
TI  - Grip strength characteristics using force-time curves in rheumatoid hands.
AB  - The use of force-time curves in rheumatoid hands was investigated to assess peak
      force, average force, total grip time, area under the curve, and variability of
      the plateau region of the curves to identify the impact of different rheumatoid
      hand deformities on grip strength. We studied 43 patients - 10 men and 33 women -
      with established rheumatoid arthritis affecting their hands. Mean age was 61
      years and mean duration of hand involvement was 13 years. Of the 86 hands, 38 had
      no finger deformity, eight had metacarpophalangeal joint ulnar deviation without
      any additional finger deformities, 16 had swan neck deformities, and 10 had
      boutonniere deformities. Fourteen hands had a combination of deformities. The
      hands with combined deformities were the weakest, had poor grip strength (34.7 N,
      SE 8), and were able to sustain grip for only a short time (22 sec, SE 3). Swan
      neck deformity also profoundly affects the magnitude (49.8 N, SE 7) and
      sustainability of grip (15 sec, SE 2). Even when only one finger had a swan neck
      deformity the mean strength was poor at 45 N. Swan neck deformity causes greater
      loss of strength than boutonniere deformity (82.7 N, SE 15). The strongest
      rheumatoid hands were those with only ulnar deviation deformities (90.8 N, SE
      14). The area under the curve best predicted disability assessed using the
      Patient Evaluation Measure.

PMID- 22357328
TI  - Traumatic ulnar translocation of the carpus: early recognition and treatment.
AB  - This study evaluated the clinical outcomes and radiographic features of
      surgically treated traumatic ulnocarpal translocation in nine patients (ten
      cases). All ligament and fracture repairs were completed within 2 months of
      injury. Seven cases were examined at a mean of 6.5 years, and information in
      three cases was obtained from medical records at a mean of 13 months after
      injury. At final evaluation, the mean disabilities of the arm, shoulder, and hand
      score was 6 (range, 0-16), and the mean Mayo modified wrist score was 76 (range,
      40-100). Ulnocarpal translocation was evident in nine of the injured wrists, six
      of which showed arthritis, and in four of the uninjured wrists. Ulnar variance
      measured negative in nine cases and neutral in one case. Pre-existing medial
      alignment of the carpus and ulnar minus variance may predispose to traumatic
      ulnocarpal translocation. Early injury repair does not assure restoration of
      radiocarpal alignment or prevent joint deterioration; however, these changes do
      not always portend a suboptimal result.

PMID- 22357330
TI  - Don't slip up! A modified technique for assessing central slip injuries.

PMID- 22357329
TI  - Adipofascial turnover flap for the coverage of the dorsum of the thumb: an
      anatomic study and clinical application.
AB  - The purpose of this report is to show how our anatomical findings have influenced
      the design of the dorsal homodigital adipofascial turnover arterial flap to the
      thumb. Thirty-six thumbs from 18 fresh cadavers were dissected at the Fer a
      Moulin Laboratoire (Paris, France) between January 1998 and March 1999. All
      branches of the proper digital artery (PDA) were identified. During the clinical
      study, from 2002 to 2008, 12 patients with dorsal thumb skin defects were treated
      with adipofascial turnover flaps. The dorsal branches of the PDA typically emerge
      at the level of the metacarpophalangeal and interphalangeal joints, 10 mm apart
      from the joint line. Based on the anatomical study, the flap could be designed
      predictably and reliably. The main advantages of dorsal adipofascial turnover
      flaps include their simplicity; the possibility of a one stage procedure;
      avoiding the use of tissue from elsewhere on the limb/body; minimal donor-site
      deformity; and avoidance of damage to the volar digital arteries.

PMID- 22357331
TI  - Closed rupture of the extensor indicis tendon: an unusual cause of swelling over
      the dorsum of the hand.

PMID- 22357332
TI  - Bilateral exertional rhabdomyolysis of the upper limb.

PMID- 22357333
TI  - Multi-needle aponeurotomy for advanced Dupuytren's disease: a 16-month follow-up
      study (MNA 2 Study).

PMID- 22357334
TI  - Management of severe Dupuytren's contracture of the proximal interphalangeal
      joint with use of a central slip facilitation device.
AB  - Thirty-eight fingers in 27 patients with Dupuytren's contracture of the proximal
      interphalangeal joint (PIPJ) in excess of 70 degrees  were treated using a staged
      technique. The first stage involved applying a mini external fixator across the
      PIPJ for continuous extension over 6 weeks with intensive hand therapy to
      maintain mobility of the joint and help correct the deformity. Twice weekly
      during hand therapy sessions the tension of the elastic band across the mini ex
      fix was increased, allowing that full active flexion of the PIPJ against the
      elastic band could still be achieved. The second stage, 4 weeks after the
      external fixator was applied, involved an open palm technique of fasciectomy for
      the contracted cords restricting metacarpophalangeal joint movement and
      dermofasciectomy with full-thickness skin grafting over the proximal phalanx for
      bands restricting PIPJ movement. The external fixator was used to maintain active
      extension force until the graft healed. It was generally removed in the
      outpatient clinic under ring block 2 weeks after the second stage procedure. The
      patients were followed for a mean of 20.6 (6-48) months. The mean preoperative
      PIPJ deformity improved from 75 degrees  to 37 degrees  postoperatively. Overall,
      69% of results were rated as good to excellent. Only one patient reported any on
      going functional problems. There were eight cases of pin site infections and one
      case each of loose pins, osteoarthritics at the PIPJ, reflex sympathetic
      dystrophy, and disease recurrence needing PIPJ fusion. We conclude that our
      simple staged procedure is a valid alternative in the management of severe
      Dupuytren's PIPJ contracture.

PMID- 22357335
TI  - The association between oxytocin receptor gene polymorphism (OXTR) and trait
      empathy.
AB  - BACKGROUND: Oxytocin exerts well accepted effects on one of the key social
      processes: empathy. Previous researches have demonstrated that oxytocin promotes
      emotional and cognitive aspects of empathy, by exogenous administration as well
      as on gene level. However, the effect of diverse gene locus haplotypes of
      oxytocin receptor gene (OXTR) on trait empathy lacks reliable evidence. METHODS:
      Participants consisted of 101 genetically unrelated, non-clinical Chinese
      subjects (46 males and 55 females). Interpersonal Reactivity Index (IRI) was
      applied to measure the trait empathy from four dimensions: empathy concern,
      personal distress, perspective taking and fantasy. Fantasy and perspective taking
      measured cognitive aspect of empathy, while empathy concern and personal distress
      measured emotional aspect of empathy. Ten single tagging SNPs on OXTR rs2268491,
      rs1042778, rs53576, rs7632287, rs2254298, rs13316193, rs237897, rs237887,
      rs4686302, and rs2268493 were tested. RESULTS: Genotype difference in emotional
      empathy was found on rs237887 and rs4686302 whereas cognitive empathy varied on
      SNPs rs2268491 and rs2254298 between homozygous and variant carriers. For IRI
      score, there is a genotype and gender interaction on rs4686302 and rs13316193.
      LIMITATION: The sample sizes from the current study were not so optimal that
      these results should have to be interpreted with caution when amplified into a
      larger population. CONCLUSION: The findings demonstrate that natural variants of
      OXTR associated with trait empathy; specifically, individuals with certain OXTR
      genotype did perform better on trait empathy, while others did not. Our findings
      also provide genetic evidence for gender-related difference on empathy,
      indicating the popular fact that females who displayed more empathy than males
      could be likely to trace back to the genetic variants.

PMID- 22357336
TI  - Belief in the harmfulness of antidepressants: associated factors and change over
      16 years.
AB  - BACKGROUND: Negative views of psychiatric medications are a common in many
      countries and efforts have been made to improve these. Relatively little is known
      of the changes in beliefs about harmfulness of antidepressant medications.
      METHODS: A 2011 national survey of 2024 Australian adults assessed beliefs about
      the helpfulness or harmfulness of antidepressants for a person who is depressed
      or depressed/suicidal and the associations with sociodemographic characteristics,
      exposure to depression, recognition of depression, and beliefs about other
      interventions, long-term outcomes, causes, and stigmatising attitudes. Changes in
      attitudes since previous surveys (conducted in 1995 and 2003/2004) were also
      assessed. RESULTS: Approximately 20% of Australian adults believe that
      antidepressants would be harmful for a person who is depressed or
      depressed/suicidal. This group was more likely to be male, born overseas, have
      less exposure to depression, show poorer depression recognition, have less
      positive views about other standard interventions, be less pessimistic about long
      term outcomes and have greater stigmatising attitudes. Comparison with previous
      surveys showed that overall belief in the harmfulness of antidepressants for
      depression decreased between 1995 and 2003/2004 and between 1995 and 2011,
      particularly in young people and in those with a lower level of education.
      LIMITATIONS: The study did not explore the reasons for belief in harmfulness.
      CONCLUSIONS: Belief in the harmfulness of antidepressants for depression fell in
      the 16 years prior to 2011. The higher proportions of males and those from non
      English speaking backgrounds believing in harmfulness suggest that education
      about the role of antidepressants in the treatment of depression should focus on
      these groups.

PMID- 22357337
TI  - Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of
      non-suicidal elderly depressed patients.
AB  - BACKGROUND: The prefrontal cortex (PFC) is presumed to be involved in the
      pathogenesis of depression. METHODS: We determined the gene expression of 32
      markers of the pathways of the two main neurotransmitters of the PFC, gamma
      aminobutyric acid (GABA) and l-glutamic acid (glutamate), by real-time
      quantitative PCR in human postmortem anterior cingulate cortex (ACC) and
      dorsolateral PFC (DLPFC) in elderly non-suicidal patients with major depressive
      disorder (MDD) or bipolar disorder (BD). RESULTS: We found the transcript levels
      of GABA(A) receptor beta 2 (GABRB2) and post-synaptic density-95 (PSD-95) to be
      significantly decreased in the ACC in mood disorder. DLPFC mRNA expression of all
      the detected genes in the mood disorder group did not differ significantly from
      that of the non-psychiatric controls. LIMITATIONS: Several inherent and
      potentially confounding factors of a postmortem study, such as medication and
      cause of death, did not seem to affect the conclusions. The group size was
      relatively small but well documented, both clinically and neuropathologically.
      CONCLUSIONS: The observed alterations in the GABAergic and glutamatergic pathways
      indicate a diminished activity. These alterations were only present in the ACC
      and not in the DLPFC.

PMID- 22357339
TI  - Pathobiology of focal segmental glomerulosclerosis:  new developments.
AB  - PURPOSE OF REVIEW: Focal segmental glomerulosclerosis (FSGS) is a major cause of
      nephrotic syndrome and renal failure. All forms of FSGS share podocyte injury and
      depletion as central mediators. This review focuses on new insights into
      pathogenesis from study of extrinsic toxins in experimental models, permeability
      factors in human disease, and novel genetic causes. RECENT FINDINGS: Experimental
      toxin models have advanced our understanding of the threshold and dynamics of
      podocyte injury. Following initial podocyte depletion, spreading fields of
      podocyte injury through secondary mediators appear to be important in generating
      the segmental pathologic lesions. Proliferating glomerular epithelial cells are
      common in FSGS, although there are conflicting views about their identity.
      Evidence suggests potential contributions by mature parietal epithelial cells,
      facultative stem cells and podocytes. A number of novel candidate permeability
      factors that affect podocyte function and motility have been discovered in human
      FSGS and related podocytopathy minimal change disease. Exome capture has
      identified new monogenic causes of familial FSGS. Apolipoprotein L-1 (APOL1) is
      expressed in podocytes, and the prevalence of APOL1 risk alleles in patients of
      African descent with primary FSGS and HIV-associated nephropathy is high,
      implicating potential podocyte effects. SUMMARY: FSGS is caused by a complex
      interplay of inherent genetic susceptibilities and external injurious factors
      acting on podocytes. Critical levels of podocyte stress eventuate in podocyte
      depletion, segmental glomerular scarring, and glomerular epithelial cell
      hyperplasia.

PMID- 22357338
TI  - Mood disorder symptoms and elevated cardiovascular disease risk in patients with
      bipolar disorder.
AB  - OBJECTIVES: We examined the association between mood symptoms and 10-year CVD
      risk estimated by Framingham risk score in a cohort of patients with bipolar
      disorder. METHODS: Veterans with bipolar disorder and CVD risk factors (N=118)
      were recruited from outpatient VA clinics. CVD risk factor data were collected
      from electronic medical records and patient surveys, and used to calculate
      patient Framingham Scores. The relationship between mood symptoms (depressive,
      manic) and Framingham scores was examined, as was the relationship between mental
      health symptoms and individual CVD risk factors (lipids, blood pressure, weight,
      smoking, and fasting glucose). RESULTS: Mean sample age was 53 years (SD=9.9),
      17% were female, and 5% were African-American. Almost 70% were obese (BMI>=30),
      84% had hyperlipidemia, 70% were hypertensive, and 25% had diabetes. Nineteen
      percent had a Framingham score of >20%, indicative of elevated 10-year risk of
      developing CVD. After adjusting for age, gender, diabetes diagnosis, smoking
      status, and mood symptoms, patients with clinically significant depressive
      symptoms had a 6-fold increased odds of having a Framingham score of >20%
      (OR=6.1, p=0.03) while clinically significant manic symptoms were not associated
      with the Framingham score (OR=0.6, p=0.36). Depressive symptoms were also
      associated with elevated BMI, fasting glucose, and blood pressure. LIMITATIONS:
      Single-site study reliant on cross-sectional and self-reported mood measures.
      CONCLUSION: After controlling for physiologic correlates, depressive symptoms
      were associated with greater relative 10-year risk for CVD mortality among
      patients with bipolar disorder. Interventions that address self-management of
      depressive symptoms may help persons with bipolar disorder decrease CVD risk.

PMID- 22357340
TI  - Synthesis and cytotoxicity of diam(m)ineplatinum(II) complexes with 2,2
      bis(hydroxymethyl)malonate as the leaving group.
AB  - Six diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the
      leaving group were synthesized and characterized by elemental analysis, FAB-MS,
      FT-IR, (1)H and (13)C NMR along with a single crystal X-ray diffraction for a
      representative compound. All the complexes were evaluated for the cytotoxicity
      against human cancer cell lines A549/ATCC, HT-29, SGC-7901. The activity is
      related to the nature of the am(m)ine ligand. cis-[Pt(II)(1R,2R
      Diaminocyclohexane).2,2-bis(hydroxymethyl)malonate] (complex 5) exhibits the
      greatest activity among those six complexes, and is even more active than its
      parent compound oxaliplatin. LD(50) was found to be 115 mg/kg by iv
      administration to ICR mice, much larger than that of oxaliplatin (LD(50)=19
      mg/kg).

PMID- 22357341
TI  - Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as
      neuroprotective agents.
AB  - A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides
      were synthesized. The neuroprotective effects of these steroidal compounds
      against amyloid-beta(25-35) (Abeta(25-35))- and hydrogen peroxide (H(2)O(2))
      induced neurotoxicity in PC12 cells, and oxygen-glucose deprivation (OGD)-induced
      neurotoxicity in SH-SY5Y cells were evaluated. The bioassay results indicated
      that several 3beta-pregn-21-benzylidene-20-one derivatives displayed potent in
      vitro neuroprotective effects in different screening models, for example,
      compounds 2b, 3a, 3b, and 3s showing significant activities against Abeta(25-35)
      induced neurotoxicity in PC12 cells, 2b showing significant activities against
      H(2)O(2)-induced neurotoxicity in PC12 cells, and 2g, 3b, and 3e showing potent
      protection against OGD insult. The results suggested that introduction of an
      arylidene group into steroidal nucleus played an important role in
      neuroprotective activity, while the formation of epoxy group at C-5,6 could be
      also important for the neuroprotective activity in some degree. The
      pharmacological data reported here are helpful for the design of novel steroidal
      neuroprotective candidates.

PMID- 22357342
TI  - SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as MU
      opioid ligands.
AB  - 3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral MU opioid
      receptor ligands for the treatment of pruritus in dogs. In this paper, we
      describe the SAR of this class of opioid ligand, highlighting changes to the lead
      structure which led to compounds having picomolar binding affinity, selective for
      the MU receptor over delta and kappa subtypes. Some subtleties of functional
      activity will also be described.

PMID- 22357343
TI  - Prolactin and growth hormone aggregates in secretory granules: the need to
      understand the structure of the aggregate.
AB  - Prolactin and GH form reversible aggregates in the trans-Golgi lumen that become
      the dense cores of secretory granules. Aggregation is an economical means of
      sorting, because self-association removes the hormones from other possible
      pathways. Secretory granules containing different aggregates show different
      behavior, such as the reduction in stimulated release of granules containing
      R183H-GH compared with release of those containing wild-type hormone. Aggregates
      may facilitate localization of membrane proteins necessary for transport and
      exocytosis of secretory granules, and therefore understanding their properties is
      important. Three types of self-association have been characterized: dimers of
      human GH that form with Zn(2+), low-affinity self-association of human prolactin
      caused by acidic pH and Zn(2+) with macromolecular crowding, and amyloid fibers
      of prolactin. The best candidate for the form in most granules may be low
      affinity self-association because it occurs rapidly at Zn(2+) concentrations that
      are likely to be in granules and reverses rapidly in neutral pH. Amyloid may form
      in older granules. Determining differences between aggregates of wild type and
      those of R183H-GH should help to understand why granules containing the mutant
      behave differently from those containing wild-type hormone. If reversible
      aggregation of other hormones, including those that are proteolytically
      processed, is the crucial act in forming granules, rather than use of a sorting
      signal, then prohormones should form reversible aggregates in solution in
      conditions that resemble those of the trans-Golgi lumen, including macromolecular
      crowding.

PMID- 22357344
TI  - Vein Patterning 1-encoded progesterone 5beta-reductase: activity-guided
      improvement of catalytic efficiency.
AB  - Progesterone 5beta-reductases (P5betaR; EC 1.3.99.6) encoded by Vein Patterning 1
      (VEP1) genes are capable of reducing the CC double-bond of a variety of enones
      enantioselectively. Sequence and activity data of orthologous P5betaRs were used
      to define a set of residues possibly responsible for the large differences in
      enzyme activity seen between rAtSt5betaR and rDlP5betaR, recombinant forms of
      P5betaRs from Arabidopsis thaliana and Digitalis lanata, respectively. Tyrosine
      156, asparagine-205 and serine-248 were identified as hot spots in the rDlP5betaR
      responsible for its low catalytic efficiency. These positions were individually
      substituted for amino acids found in the strong rAtSt5betaR in the corresponding
      sites. Kinetic constants were determined for rDlP5betaR and its mutants as well
      as for rAtSt5betaR using progesterone and 2-cyclohexen-1-one as substrates.
      Enzyme mutants in which asparagine-205 was substituted for methionine or alanine
      showed considerably lower km and higher K(cat)/k(m) values than the wild-type
      DlP5betaR, approaching the catalytic efficiency of strong P5betaRs. The
      introduced mutations not only lead to an improved capability to reduce
      progesterone but also to altered substrate preference. Our findings provided
      structural insights into the differences seen among the natural P5betaRs with
      regard to their substrate preferences and catalytic efficiencies.

PMID- 22357345
TI  - Systematic criteria for type and screen based on procedure's probability of
      erythrocyte transfusion.
AB  - BACKGROUND: At many hospitals, the type and screen decision is guided by the
      hospital's maximum surgical blood order schedule, a document that includes for
      each scheduled (elective) surgical procedure a recommendation of whether a
      preoperative type and screen be performed. There is substantial heterogeneity in
      the scientific literature for how that decision should be made. METHODS:
      Anesthesia information management system data were retrieved from the 160,207
      scheduled noncardiac cases in adults of 1,253 procedures at a hospital. RESULTS:
      Neither assuming a Poisson distribution of mean erythrocyte units transfused, nor
      grouping rare procedures into larger groups based on their anesthesia Current
      Procedural Terminology code, was reliable. In contrast, procedures could be
      defined to have minimal estimated blood loss (less than 50 ml) based on low
      incidence of transfusion and low incidence of the hemoglobin being checked
      preoperatively. Among these procedures, when the lower 95% confidence limit for
      erythrocyte transfusion was less than 5%, type and screen was shown to be
      unnecessary. The method was useful based on including multiple differences from
      the hospital's maximum surgical blood order schedule and clinicians' test
      ordering (greater than or equal to 29% fewer type and screen). Results were the
      same with a Bayesian random effects model. CONCLUSIONS: We validated a method to
      determine procedures on the maximum surgical blood order schedule for which type
      and screen was not indicated using the estimated blood losses and incidences of
      transfusion.

PMID- 22357346
TI  - Case scenario: nerve injury after knee arthroplasty and sciatic nerve block.

PMID- 22357347
TI  - The MU-opioid receptor in cancer progression: is there a direct effect?

PMID- 22357348
TI  - Schizophrenia patients with a history of childhood trauma have a pro-inflammatory
      phenotype.
AB  - BACKGROUND: Increasing evidence indicates that childhood trauma is a risk factor
      for schizophrenia and patients with this syndrome have a pro-inflammatory
      phenotype. We tested the hypothesis that the pro-inflammatory phenotype in
      schizophrenia is associated with childhood trauma and that patients without a
      history of such trauma have a similar immune profile to healthy controls. METHOD:
      We recruited 40 schizophrenia patients and 40 controls, all of whom completed the
      Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay
      (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1beta, IL
      6, IL-8 and tumour necrosis factor (TNF)-alpha. These immune parameters were
      compared in schizophrenia with childhood trauma, schizophrenia without childhood
      trauma and healthy controls. RESULTS: Patients with childhood trauma had higher
      levels of IL-6 and TNF-alpha than patients without trauma and healthy controls,
      and TNF-alpha levels correlated with the extent of the trauma. Patients with no
      trauma had similar immune profiles to controls. CONCLUSIONS: Childhood trauma
      drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.

PMID- 22357349
TI  - The unexpected always happens.

PMID- 22357350
TI  - The value of early second trimester PAPP-A and ADAM12 in screening for pre
      eclampsia.
AB  - OBJECTIVE: To estimate the pre-eclampsia screening performance of PAPP-A
      (pregnancy-associated plasma protein-A) and ADAM12 (A Disintegrin And
      Metalloprotease 12) in the early second trimester of pregnancy. METHODS: Stored
      frozen serum samples from a previously published nested case-control study
      comprising 77 women who developed pre-eclampsia and 224 unaffected controls were
      thawed and assayed for PAPP-A and ADAM12. Levels were converted into multiple of
      the unaffected median (MoM) values. RESULTS: Neither PAPP-A or ADAM12 were
      significantly different in women who developed pre-eclamspia compared with
      unaffected controls (PAPP-A: 0.97 MoM [95% confidence interval 0.73 to 1.25],
      ADAM12: 1.01 MoM [0.91 to 1.13]). CONCLUSION: Our results do not support the use
      of PAPP-A or ADAM12 in early second trimester antenatal screening for pre
      eclampsia.

PMID- 22357351
TI  - Adding ductus venosus blood flow as a categorical variable to the Combined and
      Integrated tests in Down's syndrome screening.
AB  - Ductus venosus blood flow, expressed as a pulsatility index (DVPI) has been shown
      to improve the performance of the Combined and Integrated antenatal screening
      tests for Down's syndrome using previously published data. The use of ductus
      venosus blood flow as a categorical marker (reversed or absent end diastolic
      blood flow indicating a positive result) is less discriminatory but simpler, so
      is sometimes preferred over DVPI. For example, with the Integrated test the false
      positive rate for a 90% detection rate was 1.5% as a categorical marker compared
      with 1.1% expressed as DVPI.  We here provide the necessary algorithm and
      parameters for using ductus venosus blood flow as a categorical marker with the
      Combined and Integrated tests.

PMID- 22357353
TI  - Human resources for health care delivery in Tanzania: a multifaceted problem.
AB  - BACKGROUND: Recent years have seen an unprecedented increase in funds for
      procurement of health commodities in developing countries. A major challenge now
      is the efficient delivery of commodities and services to improve population
      health. With this in mind, we documented staffing levels and productivity in
      peripheral health facilities in southern Tanzania. METHOD: A health facility
      survey was conducted to collect data on staff employed, their main tasks,
      availability on the day of the survey, reasons for absenteeism, and experience of
      supervisory visits from District Health Teams. In-depth interview with health
      workers was done to explore their perception of work load. A time and motion
      study of nurses in the Reproductive and Child Health (RCH) clinics documented
      their time use by task. RESULTS: We found that only 14% (122/854) of the
      recommended number of nurses and 20% (90/441) of the clinical staff had been
      employed at the facilities. Furthermore, 44% of clinical staff was not available
      on the day of the survey. Various reasons were given for this. Amongst the
      clinical staff, 38% were absent because of attendance to seminar sessions, 8%
      because of long-training, 25% were on official travel and 20% were on leave. RCH
      clinic nurses were present for 7 hours a day, but only worked productively for
      57% of time present at facility. Almost two-third of facilities had received less
      than 3 visits from district health teams during the 6 months preceding the
      survey. CONCLUSION: This study documented inadequate staffing of health
      facilities, a high degree of absenteeism, low productivity of the staff who were
      present and inadequate supervision in peripheral Tanzanian health facilities. The
      implications of these findings are discussed in the context of decentralized
      health care in Tanzania.

PMID- 22357354
TI  - Facial perception bias in patients with major depression.
AB  - This study used a morphed categorical perception facial expression task to
      evaluate whether patients with depression demonstrated deficits in distinguishing
      boundaries between emotions. Forty-one patients with depression and 41 healthy
      controls took part in this study. They were administered a standardized set of
      morphed photographs of facial expressions with varying emotional intensities
      between 0% and 100% of the emotion, in 10% increments to provide a range of
      intensities from pleasant to unpleasant(e.g. happy to sad, happy to angry) and
      approach-avoidance (e.g. angry to fearful). Compared with healthy controls, the
      patients with depression demonstrated a rapid perception of sad expressions in
      happy-sad emotional continuum and demonstrated a rapid perception of angry
      expressions in angry-fearful emotional continuum. In addition, when facial
      expressions shifted from happy to angry, the depressed patients had a clear
      demarcation for the happy-angry continuum. Depressed patients had a perceptual
      bias towards unpleasant versus pleasant expressions and the hypersensitivity to
      angry facial signals might influence the interaction behaviors between depressed
      patients and others.

PMID- 22357355
TI  - Shame and guilt/self-blame as predictors of expressed emotion in family members
      of patients with schizophrenia.
AB  - Expressed emotion (EE) is a measure of the family environment reflecting the
      amount of criticism and emotional over-involvement expressed by a key relative
      towards a family member with a disorder or impairment. Patients from high EE
      homes have a poorer illness prognosis than do patients from low EE homes. Despite
      EE's well-established predictive validity, questions remain regarding why some
      family members express high levels of EE attitudes while others do not. Based on
      indirect evidence from previous research, the current study tested whether shame
      and guilt/self-blame about having a relative with schizophrenia serve as
      predictors of EE. A sample of 72 family members of patients with schizophrenia
      completed the Five Minute Speech Sample to measure EE, along with questionnaires
      assessing self-directed emotions. In line with the hypotheses, higher levels of
      both shame and guilt/self-blame about having a relative with schizophrenia
      predicted high EE. Results of the current study elucidate the EE construct and
      have implications for working with families of patients with schizophrenia.

PMID- 22357356
TI  - Depressive tendencies and pathological narcissism among psychiatric outpatients.
AB  - This study examined the relationship between components of pathological
      narcissism and types of depressive tendencies among a sample of 117 psychiatric
      outpatients. Findings revealed that depressive themes concerning dependency were
      associated with narcissistic grandiosity. Depressive tendencies concerning self
      criticism were positively associated with narcissistic vulnerability.

PMID- 22357357
TI  - Different measures of impulsivity in patients with anxiety disorders: a case
      control study.
AB  - The relationship between anxiety and impulsivity is controversial and not well
      explored. The present investigation aims to compare impulsivity, measured by
      different rating tools, in patients with anxiety disorders vs. healthy controls.
      Forty-seven subjects with different anxiety disorders and 45 matched controls
      underwent diagnostic and symptomatological evaluations by the Mini
      Neuropsychiatric Interview (M.I.N.I) Plus 5.0, Bech-Raphaelsen Depression and
      Mania Scale (BRDMS), State-Trait Anxiety Inventory (STAI), Hypomania Check List
      (HCL-32) and the Clinical Global Impression (CGI); temperamental evaluations by
      the Questionnaire for the Affective and Anxious Temperament Evaluation of
      Memphis, Pisa, Paris and San Diego-Modified (TEMPS-M), the Separation Anxiety
      Sensitivity Index (SASI), the Interpersonal Sensitivity Symptoms Inventory
      (ISSI); and psychometric and a neurocognitive evaluations of impulsivity using
      the Barratt Impulsiveness Scale (BIS-11) and the Immediate and Delayed Memory
      Task (IMT-DMT). Subjects with anxiety disorders were more impulsive than the
      controls in all the explored measures, with higher scores in symptomatological
      and, temperamental scales. Patients with anxiety disorders but without a lifetime
      history of comorbid major mood episodes had greater trait and state impulsivity
      than controls. Further investigations are needed to assess the extent to which
      impulsivity might or might not be directly related to the anxiety disorder.

PMID- 22357358
TI  - Novel small-molecular therapeutics for rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Since the introduction of biologic therapies into the
      treatment paradigm of rheumatoid arthritis (RA), there has been hope that oral
      small molecule immune modulators would be developed that would have a risk :
      benefit profile at least similar to biologic therapies, be more convenient for
      the patient and, hopefully, be less expensive. This article reviews the progress
      made in the development of these compounds over the past year. RECENT FINDINGS:
      Additional information has become available in the past year on five oral
      compounds including kinase inhibitors (tofacitinib, fostamatinib, VX-509), an S1P
      lyase inhibitor (LX 3305) and a chemokine receptor-1 antagonist (CCX354-C).
      Efficacy has been shown in phase III with tofacitinib and in phase II with
      fostamatinib and VX-509; safety was the primary endpoint of the trials of CCX354
      C and LX3305. Regarding side effects, liver test elevation and neutropenia
      occurred with tofacitinib, VX-509 and fostamatinib; lipid elevation with
      tofacitinib and VX-509; creatinine elevation and anemia with tofacitinib, and
      hypertension and diarrhea with fostamatinib. SUMMARY: Compounds that inhibit
      tyrosine kinase pathways involved in cellular signalling have been shown to be
      effective in the treatment of RA with a reasonable risk : benefit ratio. It is
      too early to tell about inhibitors of other pathways.

PMID- 22357359
TI  - Catalytic activity of baker's yeast in a mediatorless microbial fuel cell.
AB  - The catalytic activity of baker's yeast, Saccharomyces cerevisiae, as a
      biocatalyst was investigated in a mediatorless microbial fuel cell. The yeast
      cells that adhered on the anode surface were the active biocatalyst for glucose
      oxidation in a mediatorless biofuel cell, suggesting that the electron transfer
      took place through the surface confined species. The species in the anolyte
      solution including the dispersed yeast cells did not take a part in the electron
      transfer and thus in the power generation.

PMID- 22357360
TI  - Influence of polymer-surfactant aggregates on fluid flow.
AB  - This paper describes the influence of interactions of poly(ethylene oxide) (PEO)
      with cationic cetyltrimethylammonium bromide (CTAB) micelles on drag reduction.
      Since the interactions between PEO and CTAB micelles alone are weak, salicylate
      ions were used as CTAB counterions. They facilitate formation of polymer-micelle
      aggregates by screening the electrostatic repulsions between the charged
      surfactant headgroups. The influence of polymer-surfactant interactions on drag
      reduction is of biomedical engineering importance. Drag reducing additives
      introduced to blood produce beneficial effects on blood circulation, representing
      a novel way to treat cardiovascular disorders. PEO is a blood-compatible polymer.
      However, it quickly mechanically degrades when subjected to high shear stresses.
      Thus, there is a need to search for other additives able to reduce drag, which
      would be more mechanically stable, e.g. polymer-surfactant aggregates. Numerical
      simulations of the flow were performed using the CFX software. Based on the
      internal structure of the polymer-surfactant solution, a hypothesis explaining
      the reason of increase of drag reduction and decrease in dynamic viscosity with
      increasing shear rate was proposed. It was suggested that the probable reason for
      the abrupt increase in friction factor, observed when the critical Reynolds
      number was exceeded, was the disappearance of the difference in the dynamic
      viscosity.

PMID- 22357362
TI  - Atherogenesis and diabetes: focus on insulin resistance and hyperinsulinemia.

PMID- 22357361
TI  - Heart failure in acute myocardial infarction: a comparison between patients with
      or without heart failure criteria from the FAST-MI registry.
AB  - INTRODUCTION AND OBJECTIVES: To compare acute myocardial infarction patients with
      or without congestive heart failure in the French FAST-MI registry. METHODS: The
      French FAST-MI registry included 374 centers and 3059 patients over a 1-month
      period at the end of 2005, with 1-year follow-up. Among this population, patients
      with at least one congestive heart failure criterion constituted group 1 (n=1149;
      37.5%) and were compared to patients without congestive heart failure (group 2,
      n=1910; 62.5%). The congestive heart failure patients were further divided
      according to presence of both beta-blockers and antagonists of the renin
      angiotensin-aldosterone system at hospital discharge (n=511) or not (n=498), in
      order to assess the real-world clinical importance of recommended medications.
      RESULTS: Overall in-hospital and 1-year mortality rates were 3.4% and 13.2%,
      respectively. In hospital survivors, presence of congestive heart failure was
      associated with increased mortality (adjusted hazard ratio: 1.55; 95% confidence
      interval, 1.10-2.17; P=.01). Survival was higher in patients without congestive
      heart failure, compared with congestive heart failure patients receiving or not
      recommended medications (P<.001). Congestive heart failure patients receiving
      neither renin-angiotensin-aldosterone system blockers nor beta-blockers (adjusted
      hazard ratio: 1.66; 95% confidence interval, 1.08-2.55; P=.02) had a
      significantly higher risk of death than patients receiving both classes of
      medications (adjusted hazard ratio: 1.16; 95% confidence interval, 0.82-1.64; not
      statistically significant). Patients receiving only one of the recommended
      classes had an intermediate risk (adjusted hazard ratio: 1.47; 95% confidence
      interval, 1.04-2.07; P=.03). CONCLUSIONS: Patients admitted for acute myocardial
      infarction with congestive heart failure criteria are still at very high risk of
      mortality. When receiving major recommended medications, they presented with
      significantly reduced mortality rates. Additional efforts should therefore be
      made to encourage the prescription of recommended medications in acute myocardial
      infarction patients with congestive heart failure.

PMID- 22357363
TI  - A case of myelopathy, myopathy, peripheral neuropathy and subcortical grey matter
      degeneration associated with recessive compound heterozygous POLG1 mutations.
AB  - This 54year old woman presented with symptoms of sensory ataxic neuropathy, with
      cerebellar features. She developed further weakness, visual disturbances with
      diplopia, dysarthria and dysphasia. After her death at 66years, she was found to
      have compound heterozygous mutations of POLG1 gene in muscle, and Southern blot
      showed low levels of multiple deletions of mitochondrial DNA. Neuropathological
      examination showed profound dorsal column and dorsal spinocerebellar tract
      degeneration, degeneration of dorsal root ganglia and Clarke's nucleus in spinal
      cord and severe predominantly sensory peripheral neuropathy. The brain showed
      severe neuronal loss and gliosis in substantia nigra, medial posterior thalamus
      and head of caudate. Excess numbers of COX-negative fibres and "ragged-red"
      fibres were found in five skeletal muscles sampled.

PMID- 22357365
TI  - Introduction: reconsidering psychiatry in the emergency department.

PMID- 22357366
TI  - First evidence of the emergence of novel putative infectious bronchitis virus
      genotypes in Cuba.
AB  - The emergence of new infectious bronchitis virus (IBV) genotypes or serotypes
      along with the poor cross-protection observed among IBV serotypes have
      complicated the avian infectious bronchitis (IB) control programs in different
      geographic regions. In Cuba, the lack of genetic information regarding IBV and
      the increasing epidemiological importance of this virus in Cuban chicken flocks
      demand further characterization of IBV isolates. In the present work, studies of
      genetic diversity and phylogenetic relationships among recent IBV isolates from
      Cuban chicken flocks showing respiratory disorders were performed. Two putative
      genotypes genetically different to the Massachusetts genotype H120 strain used in
      the Cuban vaccination program were found in the flocks assessed. In addition, a
      potential nephropathogenic IBV isolate was found by first time in Cuba.

PMID- 22357364
TI  - Mutation spectrum and phenotypic manifestation in FSHD Greek patients.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a genetic myopathy with a
      remarkable intra- and inter-familial clinical heterogeneity. This study reports
      the clinical and genetic analysis of 133 individuals from 71 unrelated Greek
      families based on a revised clinical severity score (rCSS) index which was
      developed for clinical assessment regarding the disease progression. A high ratio
      (31/62, 50%) of probands' family members was found to be asymptomatic or
      minimally affected gene carriers of a contracted 4q allele. Moreover, a notable
      clinical variability of FSHD is reported concerning the detection of an identical
      de novo 13 b EcoRI fragment in monozygotic twins, as well as indications of
      founder effect. This is the first survey that presents data of FSHD families from
      an East Mediterranean country supporting the speculation that the prevalence of
      disease might be significantly underestimated and that synergistic factors could
      play an essential role on the progression of the disease.

PMID- 22357367
TI  - Empirical time dependence of liquid self-diffusion coefficient in porous media.
AB  - A new method of finding experimental time dependence of the self-diffusion
      coefficient D(t) for fluid in the porous media is proposed. We investigate the
      time-dependent self-diffusion coefficient D(t) of random walkers in permeable
      porous media. D(t) is measured in pulse field gradient (PFG) experiments with
      fluid-saturated porous media of randomly packed spherical glass beads. In absence
      of the specific interactions between pore walls and a fluid we show that D(t) =
      (D(0) - D(infinity))exp(-F?(D(0)t)/d) + D(infinity), where D(0) is the diffusion
      constant in a bulk fluid, D(infinity) is the asymptotical value of the diffusion
      coefficient for long diffusion times (t->infinity), d is the bead diameter and F
      is the constant characterizing the geometry (the size and shape) pores.

PMID- 22357368
TI  - Current certainties and future developments in the use of the anaesthetic
      conserving device (AnaConDa).

PMID- 22357369
TI  - Assessing sedation in PICU: clinical scales or BIS analysis?

PMID- 22357370
TI  - Microcirculation after cardiopulmonary bypass: a glance at the mesenteric mucosa.

PMID- 22357371
TI  - Argatroban anticoagulation for heparin induced thrombocytopenia in patients with
      ventricular assist devices.
AB  - BACKGROUND: Patients receiving implantation of ventricular assist devices (VAD)
      suffer a high incidence of heparin induced thrombocytopenia (HIT); the occurrence
      of this condition is associated with increased complications and worse outcomes.
      We report our experience in the management of patients who were diagnosed with
      HIT either before (HITpre) or after (HITpost) implantation of VAD with
      argatroban, a direct thrombin inhibitor. METHODS: This retrospective analysis
      assessed data of VAD patients diagnosed with HIT at Deutsches Herzzentrum Berlin
      between November 2005 and April 2009. Argatroban dose requirements,
      anticoagulation efficacy and adverse events (death, thromboembolism, bleeding)
      were recorded. Procedural success (discharge from the hospital, heart
      transplantation, or recovery of the failing heart) was also assessed. RESULTS:
      Twenty-seven patients were identified (11 HITpre, 16 HITpost). Argatroban was
      effective in obtaining adequate anticoagulation with a reduced dose regimen (0.02
      0.42 mcg/Kg/min starting dose; 0.02-1.5 mcg/Kg/min maintenance dose). We noted 5
      thromboembolic complications (18%), 6 cases of major bleeding (22%) and 5 deaths
      (18%), all cause composite adverse end point occurring in 40% of patients.
      Procedural success was obtained in 81% of patients (92% HITpre, 69% HITpost). As
      compared to historical controls of patients treated with lepirudin in the period
      2000-2005, results were significantly improved. CONCLUSION: Argatroban
      anticoagulation is feasible in patients with HIT after VAD implantation, without
      increasing bleeding risk. Its impact in terms of survival should be reviewed also
      in the light of the technological improvements of assist devices.

PMID- 22357372
TI  - Acute respiratory distress syndrome: evaluation and management.
AB  - Acute respiratory distress syndrome (ARDS) is a life-threatening condition that
      affects patients admitted in the Intensive Care Units (ICUs) under mechanical
      ventilation. ARDS is a process of non-hydrostatic pulmonary edema and hypoxemia
      associated with a variety of conditions, resulting in a direct (e.g., pneumonia)
      or indirect (e.g., sepsis) lung injury and is associated with a significant
      morbidity and mortality. A large body of clinical and basic research has focused
      in ventilatory strategies and novel pharmacological therapies but, nowadays,
      treatment is mainly supportive. Mechanical ventilation is the hallmark of the
      management of these patients. In the last decades, the recognition that
      mechanical ventilation can contribute to harming the lung has changed the goals
      of this therapy and has driven research to focus in ventilatory strategies that
      mitigate lung injury. This review emphasizes clinical aspects in the evaluation
      and management of ARDS in the ICUs and updates the latest advances in these
      therapies.

PMID- 22357374
TI  - Mobile phone communication and health system strengthening: a pilot study of
      telephonic warmline consultation in HIV care and support in South India.
AB  - INTRODUCTION: I-TECH India established a warmline pilot in the year 2008 to
      provide mobile-based technical support on clinical management to doctors caring
      for HIV patients in antiretroviral therapy (ART) centers. METHODS: Warmline was
      piloted from May to August 2008. Standardized call records were analyzed.
      Statistical analyses were performed using SPSS. RESULTS: The service was used by
      38 doctors. The study demonstrated the frequency of calls and the nature of
      questions raised by them. Of the calls, 139 were new calls (90.3%) and 15 were
      follow-up calls. The average number of calls per day was 2.6 (SD 1.6). Of the
      total number, 81% of the calls were from high-volume centers. Most of the calls
      were related to ARV toxicities, ART initiation, and the management of
      opportunistic infections (OI). CONCLUSION: The South Indian warmline pilot
      demonstrated a potential model of ongoing technical assistance to ART doctors in
      times of need. AIDS-control organizations may consider expanding this model of
      expert distance-mentoring clinical support as a resource in India and other
      countries.

PMID- 22357373
TI  - Perioperative use of prothrombin complex concentrates.
AB  - Prothrombin complex concentrates (PCCs) are purified drug products with
      hemostatic activity derived from a plasma pool. Today, PCCs contain a given and
      proportional amount of four non-activated vitamin K-dependent coagulation factors
      (II, VII, IX, and X), a variable amount of anticoagulant proteins (proteins C and
      S, and in some antithrombin) and low-dose heparin. In some countries PCC products
      contained only three clotting factors, II, IX, and X. Dosage recommendations are
      based on IU of F-IX, so that one IU of F-IX represents the activity of F-IX in 1
      mL of plasma. Reversion of the anticoagulant effect of vitamin K antagonists
      (VKAs) in cases of symptomatic overdose, active bleeding episodes, or need for
      emergency surgery is the most important indication for PCCs and this effect of
      PCCs appears to be more complete and rapid than that caused by administration of
      fresh frozen plasma. They may be considered as safe preparations if they are used
      for their approved indications at the recommended dosage with adequate
      precautions for administration, and have been shown to be effective for reversing
      the effect of VKAs. Their adequate use based on decision algorithms in the
      perioperative setting allows a rapid normalization of International Normalized
      Ratio (INR) for performing emergency surgery, minimizing bleeding risk. This
      review aims to propose two algorithms for the use of PCCs in the perioperative
      setting, one to calculate the PCCs dose to be administered in a bleeding patient
      and/or immediately before urgent surgery, based on patient's clinical status,
      prior INR and INR target and another for reversing the action of oral
      anticoagulants depending on urgency of surgery.

PMID- 22357375
TI  - Rupture of a giant aneurysm of the pulmonary artery caused by schistosomiasis.

PMID- 22357376
TI  - Brain volume reductions in medication-naive patients with schizophrenia in
      relation to intelligence quotient.
AB  - BACKGROUND: Global brain abnormalities such as brain volume loss and grey- and
      white-matter deficits are consistently reported in first-episode schizophrenia
      patients and may already be detectable in the very early stages of the illness.
      Whether these changes are dependent on medication use or related to intelligence
      quotient (IQ) is still debated. METHOD: Magnetic resonance imaging scans were
      obtained for 20 medication-naive patients with first-episode schizophrenia and 26
      matched healthy subjects. Volume measures of total brain grey and white matter,
      third and lateral ventricles and cortical thickness/surface were obtained.
      Differences between the groups were investigated, taking into account the effect
      of intelligence. RESULTS: Medication-naive patients showed statistically
      significant reductions in whole-brain volume and cerebral grey- and white-matter
      volume together with lateral ventricle enlargement compared to healthy subjects.
      IQ was significantly lower in patients compared to controls and was positively
      associated with brain and white-matter volume in the whole group. No significant
      differences in cortical thickness were found between the groups but medication
      naive patients had a significantly smaller surface in the left superior temporal
      pole, Heschl's gyrus and insula compared to controls. CONCLUSIONS: Our findings
      suggest that brain volume loss is present at illness onset, and can be explained
      by the reduced surface of the temporal and insular cortex. These abnormalities
      are not related to medication, but IQ.

PMID- 22357377
TI  - Polysaccharides from astragali radix restore chemical-induced blood vessel loss
      in zebrafish.
AB  - BACKGROUND: Astragali Radix has been used widely for the treatment of
      cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina
      in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide
      constituents of Astragali Radix (ARP) are considered as one of the major
      constituents contributing to the multiple pharmacological effects of this
      medicinal plant. The purpose of the study is to evaluate the vascular
      regenerative activities of ARPs in a chemically-induced blood vessel loss model
      in zebrafish. METHODS: Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1
      and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase
      inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood
      vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI
      withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish
      larvae were observed under the fluorescence microscope and measured
      quantitatively. The rescue effect of ARPs in the zebrafish models was validated
      by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time
      PCR. RESULTS: Two polysaccharide fractions, P4 (50000 D < molecular weight &
      diameter < 0.1 MUm) and P5 (molecular diameter > 0.1 MUm), isolated from
      Astragali Radix by ultrafiltration, produced a significant and dose-dependent
      recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down
      regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by
      treatment with P4. CONCLUSION: The present study demonstrates that P4 isolated
      from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These
      findings support the hypothesis that polysaccharides are one of the active
      constituents in Astragali Radix, contributing to its beneficial effect on
      treatment of diseases associated with a deficiency in angiogenesis.

PMID- 22357378
TI  - Suicide prevention and emergent media: surfing the opportunity.

PMID- 22357381
TI  - Post-LASIK keratectasia triggered by eye rubbing and treated with topography
      guided ablation and collagen cross-linking--a case report.
AB  - PURPOSE: To report a case of unilateral post-laser-assisted in situ
      keratomileusis (LASIK) keratectasia in a 35-year-old woman who had no known
      predisposing risk factors but who rubbed her affected eye frequently and
      vigorously in response to allergic conjunctivitis. METHODS: Case report with
      relevant literature review. RESULTS: A 35-year-old woman, with a cumulative risk
      scale score of 0 (according to the Randleman criteria), who underwent bilateral
      LASIK developed unilateral post-LASIK keratectasia 32 months later. She presented
      with a history of vigorous eye rubbing of the affected eye since about a year
      after allergic conjunctivitis. The fellow eye, which was not rubbed, remained
      normal. She complained of glare, halos, and ghost images in her affected eye. She
      underwent transepithelial topography-guided customized ablation with simultaneous
      UV-A corneal collagen cross-linking, after which she improved symptomatically and
      topographically. CONCLUSIONS: Eye rubbing could contribute to the development of
      keratectasia, even in an eye that has no subclinical features of the disease.
      When detected early, a simultaneous combined topography-guided customized
      ablation treatment and collagen cross-linking is effective in improving the
      irregular corneal contour and restoring biomechanical stability.

PMID- 22357382
TI  - Descemet stripping endothelial keratoplasty: six-month results of the first 100
      consecutive surgeries performed solo by a surgeon using 1 technique with 100%
      follow-up.
AB  - PURPOSE: To determine the outcomes and complication rates achieved by a novice
      cornea surgeon when performing Descemet stripping automated endothelial
      keratoplasty (DSAEK) while precisely following a previously described forceps
      insertion technique. METHODS: Prospective, noncomparative interventional case
      series including 100 eyes of 74 patients with endothelial decompensation. An
      institutional review board approved, prospective, DSAEK series was initiated.
      Cases included all initial patients with endothelial failure operated on by a
      single surgeon after his cornea fellowship training. The surgeon strictly adhered
      to a previously published 5-mm incision, folded forceps graft insertion
      technique. Patients were followed at 1 day, 1 week, and 1, 3, and 6 months.
      Postoperative complications (including graft dislocation, primary graft failure,
      and pupillary block), best spectacle-corrected visual acuity (BSCVA) and specular
      microscopy of central endothelial cell density at 6 months postoperatively were
      the main outcome measures. RESULTS: One hundred consecutive eyes were enrolled in
      the study, and 100% follow-up at 6 months was achieved. Postoperative
      complications included 2 graft dislocations (2%), and both grafts were attached
      successfully and cleared; 2 episodes of cystoid macular edema (2%) occurred, and
      1 eye (1%) developed areas of anterior iris synechiae to the graft. There were no
      pupillary block episodes or primary graft failures. In eyes without comorbidity
      (n=57), the mean BSCVA improved from 20/48 preoperation to 20/29 at 6 months
      after operation (P<0.001). No eyes lost vision. Mean central endothelial cell
      density decreased from 2769 cells per square millimeter preoperatively to 2308
      cells per square millimeter postoperatively at 6 months. This represented a mean
      cell loss of 16%. CONCLUSIONS: This study demonstrates that with meticulous
      attention to a standardized forceps insertion technique, excellent outcomes with
      low rates of complications, improved BSCVA, and low endothelial cell loss can be
      achieved with DSAEK surgery.

PMID- 22357383
TI  - Decreased corneal sensitivity and abnormal corneal nerves in Fuchs endothelial
      dystrophy.
AB  - PURPOSE: To determine corneal sensitivity and evaluate corneal nerves before and
      after keratoplasty for Fuchs endothelial dystrophy. METHODS: Central corneal
      sensitivity, measured by using a Cochet-Bonnet esthesiometer in 69 eyes before
      and after different keratoplasty procedures for Fuchs dystrophy, was compared
      with that of 35 age-matched normal corneas. Corneal nerves were qualitatively
      examined by confocal microscopy in 42 eyes before and after Descemet stripping
      endothelial keratoplasty (DSEK). RESULTS: Corneal sensitivity in Fuchs dystrophy
      (4.61 +/- 1.42 cm) was lower than that of age-matched controls (5.74 +/- 0.48 cm,
      P < 0.001). Sensitivity decreased by 1 month after DSEK (2.98 +/- 2.01 cm, P <
      0.001), returned to preoperative sensitivity by 24 months (4.50 +/- 1.63 cm, n =
      33, P = 0.99), but remained lower than controls at 36 months (4.50 +/- 1.48 cm, n
      = 15, P < 0.001). Sensitivity at 36 months after penetrating keratoplasty (1.46
      +/- 1.98 cm) remained decreased compared with preoperative sensitivity (P <
      0.001). Subbasal nerves appeared sparse with abnormal branching before and
      through 36 months after DSEK. Sensitivity was lower in corneas without visible
      subbasal nerves by confocal microscopy at 12 months after DSEK (P < 0.005) than
      in corneas with visible nerves. Stromal nerves were frequently tortuous and
      formed loops in Fuchs dystrophy, and this appearance persisted in some eyes at 36
      months after DSEK. CONCLUSION: Corneal sensitivity is decreased in Fuchs
      dystrophy compared with normal and remains subnormal even at 3 years after
      endothelial keratoplasty. Decreased sensitivity is likely to be related to loss
      of subbasal nerves and abnormal nerve morphology, which persist after endothelial
      keratoplasty.

PMID- 22357384
TI  - Descemet stripping automated endothelial keratoplasty after failed penetrating
      keratoplasty.
AB  - PURPOSE: To report the rate of graft dislocation, surgical anatomic success, and
      postsurgical complications associated with Descemet stripping automated
      endothelial keratoplasty (DSAEK) after previous primary failed penetrating
      keratoplasty (PK). METHODS: Institutional review board-approved, single-center,
      retrospective chart review study of 30 eyes of 30 patients with prior failed PK
      who underwent DSAEK with a minimum of 3 months follow-up. Primary outcomes
      measured included rates of anatomic success and failure, postoperative
      complications, lenticle size, visual acuity, intraocular pressure change, and a
      report of external factors that may affect success. RESULTS: Thirty eyes of 30
      patients were identified. The primary dislocation rate was 16.7%. Five primary
      DSAEKs detached; 1 was successfully rebubbled in the office, 2 had repeat
      successful DSAEKs, and 2 failed on a second attempt and had a subsequent PK.
      Despite successful anatomic attachment, 1 eye had primary graft failure, 3 that
      cleared initially failed within 6 months, and 1 that successfully cleared had
      subsequent graft rejection resulting in failure at 6 months. The 2 eyes requiring
      PK were excluded from the visual outcomes analysis, leaving 28 eyes with
      successfully attached lenticles. At 3 months postoperatively, of the 28 eyes, 19
      showed an improvement in visual acuity, 6 had no change in vision from
      preoperative data, and 1 had worsening of vision (anatomic attachment but
      endothelial failure). Two of the 28 eyes had no data at that time point.
      CONCLUSIONS: DSAEK eyes after failed PK demonstrated improved vision with a low
      complication rate in a majority of patients. The graft dislocation rate and
      postoperative complications rates are comparable with the primary DSAEK
      dislocation rates in our own published series and in the literature.

PMID- 22357385
TI  - Graft biomechanical properties after penetrating keratoplasty in keratoconus.
AB  - PURPOSE: To measure corneal graft biomechanical properties after penetrating
      keratoplasty (PKP) in a group of keratoconic eyes using the ocular response
      analyzer (ORA) and to evaluate the relationship between donor size, donor
      recipient disparity and central graft thickness (CGT), and ORA parameters.
      METHODS: This cross-sectional study was conducted on 34 eyes of 34 keratoconus
      patients who had undergone PKP. Corneal hysteresis (CH), corneal resistance
      factor (CRF), and cornea-compensated intraocular pressure were measured at least
      6 months after complete suture removal. Two groups of donor-recipient disparity
      (0.25 vs. 0.50 mm) were compared using the independent t test. Multivariate
      regression analysis was used to investigate the correlation of donor trephine
      size and CGT with ORA parameters. Factors influencing intraocular pressure
      measured with the Goldmann applanation tonometer (IOP GAT) after PKP were
      determined using multiple regression analysis. RESULTS: Mean patient age and
      follow-up period were 29.6 +/- 6.2 years and 82.4 +/- 59.6 months, respectively.
      Mean CGT, CH, and CRF were 564.7 +/- 36.9 MUm, 10.1 +/- 2.1 mm Hg, and 10.0 +/-
      2.3 mm Hg, respectively. CH and CRF had a significant positive correlation with
      donor trephine size and CGT. Significantly greater values of CH and CRF were
      observed in the 0.5-mm disparity group compared with the 0.25-mm disparity group.
      Among the studied parameters, only CH, CRF, and cornea-compensated intraocular
      pressure had a significant positive correlation with IOP GAT. CONCLUSION: Graft
      biomechanics seem to be closer to normal values with larger grafts and greater
      donor-recipient disparity. These metrics had a significant correlation with IOP
      GAT after PKP.

PMID- 22357386
TI  - Visual function changes after punctal occlusion with the treatment of short BUT
      type of dry eye.
AB  - PURPOSE: To evaluate visual function changes after punctal plug (PP) occlusion in
      patients with short breakup time of tear film (BUT) type of dry eyes. METHODS: A
      prospective comparative study was performed in 43 eyes of 43 dry eye patients
      with short BUTbreakup time of tear film receiving PP occlusion. Patients were
      divided into 2 groups as those receiving only upper or only lower occlusion.
      Functional visual acuity measurements, tear function evaluations, and
      questionnaire on satisfaction with treatment in relation to presence of epiphora
      were performed before and 1 month after PP insertion. RESULTS: Twenty eyes of 43
      eyes (46.5%) with only lower occlusion and 17 eyes of 43 eyes (39.5%) with only
      upper occlusion showed satisfactory outcomes with treatment. One of 43 eyes (2.3
      %) had epiphora. Vital staining scores and BUT values significantly improved in
      both groups after occlusion. The mean logarithm of the minimum angle of
      resolution functional visual acuity value significantly improved only in eyes
      receiving upper PP occlusion. CONCLUSION: Upper PP occlusion seems to be
      associated not only with improvement of tear stability, vital staining scores,
      and treatment-related satisfaction but also with better quality of visual
      function.

PMID- 22357387
TI  - Changes in the corneal endothelial cell density and morphology in patients with
      type 2 diabetes mellitus: a population-based study, Sankara Nethralaya Diabetic
      Retinopathy and Molecular Genetics Study (SN-DREAMS, Report 23).
AB  - PURPOSE: To study the corneal endothelial cell density and morphological features
      in type 2 diabetic patients (cases) and compare it with nondiabetic subjects
      (controls) in a population-based cross-sectional study. METHODS: Patients were
      recruited from the Sankara Nethralaya--Diabetic Retinopathy Epidemiology and
      Molecular Genetic Study, a population-based study to estimate the prevalence of
      type 2 diabetes and diabetic retinopathy in urban Chennai, South India. Corneal
      endothelial morphological features were recorded in all subjects using noncontact
      specular microscopy and central corneal thickness was measured using ultrasound
      pachymeter. RESULTS: A total of 1191 cases and 121 controls were enrolled into
      the study. The mean corneal endothelial cell density (cells/mm(2)) was lower in
      cases than in controls (2550 +/- 326 vs. 2634 +/- 256; P = 0.001). No difference
      was observed in the mean pachymetry values, hexagonality %, and coefficient of
      variation of cell size between cases and controls. Multivariate regression
      analysis, after adjusting for age, showed the mean cell density to be lesser by
      66 cells/mm(2) (95% confidence interval, 6.3-125.9) among diabetic patients
      compared with nondiabetic subjects. CONCLUSIONS: The results of this study, from
      a large population-based sample, support the earlier theories of lower
      endothelial cell counts among subjects with type 2 diabetes mellitus in
      comparison with nondiabetic controls.

PMID- 22357388
TI  - The "silent brain syndrome" creating a severe form of the "giant fornix
      syndrome".
AB  - PURPOSE: To describe the clinical course of a patient requiring ophthalmic care
      for entropion and fungal keratitis in the setting of undiagnosed enophthalmos
      after previous ventriculoperitoneal shunting consistent with silent brain
      syndrome. METHODS: Case report. RESULTS: A 33-year-old man who had a history of
      ventriculoperitoneal shunting for an encephalocele during infancy presented
      because of ocular irritation and entropion, which was presumed to be entirely due
      to a chemical injury he had sustained 2 years before. He underwent 2 upper eyelid
      entropion repairs and developed fungal aspergilloma keratitis in the
      postoperative period. He underwent 2 penetrating keratoplasties and a limbal stem
      cell transplant but had complications with reinfection of the graft, eventually
      leading to a prephthisical painful eye. During enucleation, an aspergilloma was
      found within an enlarged superior fornix. Computed tomographic scan revealed
      severe enophthalmos with air between the lids and the globe, which was consistent
      with silent brain syndrome. CONCLUSIONS: In patients with silent brain syndrome,
      the lack of apposition between the eyelids and the globe results in entropion,
      trichiasis, lagophthalmos, and ocular irritation. This can complicate entropion
      repair and the severity of infectious keratitis. We also propose that the
      enlarged fornices seen in silent brain syndrome can also serve as a reservoir for
      infection, similar to the pathogenesis seen in the giant fornix syndrome.

PMID- 22357389
TI  - Early expression of tumor necrosis factor alpha and nuclear factor kappa B after
      Descemet stripping endothelial keratoplasty in rabbits.
AB  - PURPOSE: To investigate immune rejection after Descemet stripping endothelial
      keratoplasty (DSEK) compared with that after penetrating keratoplasty (PKP) in
      New Zealand rabbit eyes and to identify the relationship between tumor necrosis
      factor alpha (TNF-alpha) and nuclear factor kappa B (NFkappaB) and evaluate their
      involvement in graft rejection. METHODS: Sixty-nine New Zealand rabbits were
      divided into 3 groups: group A comprised the control group, which did not undergo
      either of the procedures; group B underwent DSEK; and group C underwent PKP.
      Twenty-three Chinese rabbits (46 eyes) were used as donors. The corneal
      transparency, graft placement, and anterior chamber were observed for 28 days.
      Blood serum, aqueous humor, and corneal samples were obtained on days 7, 14, 21,
      and 28 after the procedures. TNF-alpha levels were measured weekly by double
      antibody enzyme-linked immunosorbent assay. NFkappaB in the cornea was checked by
      immunofluorescence. RESULTS: There were no graft rejections in group B. Group C
      showed a 50% rejection frequency with an increase in both the TNF-alpha
      concentrations and NFkappaB expression observed at 7 days and peak levels
      observed at 28 days after PKP. TNF-alpha concentrations did not differ
      significantly (P > 0.05) between groups B and A. NFkappaB expression was slightly
      increased at 7 days and returned to normal levels by day 14 after DSEK.
      CONCLUSION: Rabbits with DSEK had a lower rejection rate than rabbits with PKP.
      NFkappaB and TNF-alpha may contribute to the early rejection of corneal
      allografts.

PMID- 22357390
TI  - Pentacam-based big bubble deep anterior lamellar keratoplasty in patients with
      keratoconus.
AB  - PURPOSE: To describe the clinical results of Pentacam-based big bubble deep
      anterior lamellar keratoplasty (DALK) to achieve an intended 90% depth of initial
      lamellar trephination. METHODS: Fifty consecutive eyes of 50 patients with
      keratoconus, keratoglobus, and anterior stromal scars were included. DALK was
      performed with the big bubble technique using a 90% intended depth for initial
      lamellar trephination based on preoperative pachymetry by Pentacam. Main outcome
      measures were success of surgery, best spectacle-corrected visual acuity,
      endothelial cell count, refractive astigmatism at 12-month follow-up, and rate of
      intra- and postoperative complications. RESULTS: In 84% of the patients (n = 42),
      Pentacam-based big bubble DALK could be performed successfully. Successful big
      bubble formation could be achieved in 80% of the patients (n = 34). In case of
      macroperforation (n = 8), surgery was converted to standard penetrating
      keratoplasty representing a conversion rate of 16%. Intraoperative
      microperforation (n = 5) could be handled by an intracameral air injection at the
      end of operation with successful completion of the lamellar procedure. No
      allograft rejection was observed. Best spectacle-corrected visual acuity improved
      from 20/125 +/- 20/160 preoperatively to 20/40 +/- 20/80 at 12-month follow-up.
      Endothelial cell count was 2102 +/- 318 cells per square millimeter
      preoperatively and 1735 +/- 420 cells per square millimeter at 12-month follow
      up. Refractive astigmatism was 7.09 +/- 3.13 diopters preoperatively and
      decreased to 4.13 +/- 2.41 diopters. CONCLUSION: Pentacam-based big bubble DALK
      using a 90% intended depth of initial lamellar trephination seems to be a safe
      and effective procedure for anterior corneal stromal disorders such as
      keratoconus. We suggest that Pentacam-based depth assessment allows for reliably
      deep initial preparation and may allow more successful bubble formation in DALK
      surgery.

PMID- 22357391
TI  - Effects of subconjunctival bevacizumab on corneal neovascularization:  results of
      a prospective study.
AB  - PURPOSE: To evaluate the effect of subconjunctival bevacizumab injections in
      patients with corneal neovascularization resulting from different ocular surface
      disorders. METHODS: Prospective case series. Twelve eyes of 11 patients with
      corneal neovascularization caused by different ocular surface disorders, such as
      healed corneal ulcers, long-standing chronic inflammatory diseases, and corneal
      ischemia secondary to burn, were included. All eyes received a single
      subconjunctival injection of 2.5 mg (0.1 mL) of bevacizumab. Morphological
      changes in neovascularization were evaluated during 3 months using slit-lamp
      biomicroscopy, corneal digital photography, and computer-assisted semiautomatic
      analysis of corneal neovascularization area. RESULTS: Recession of corneal
      vessels was observed in all eyes at 1 week postinjection. The surface of the
      neovascular tree continued to decrease noticeably for 1 month and then increased
      again for the remainder of the follow-up period. The corneal neovascularization
      area amounted to 11.25 +/- 4.49% of the corneal surface preinjection, compared
      with 8.44 +/- 3.37% postinjection (P = 0.02), reflecting a mean decrease in
      corneal neovascularization of 25%. No local or systemic adverse events possibly
      related to subconjunctival bevacizumab injection were observed. CONCLUSIONS:
      Short-term results suggest that subconjunctival bevacizumab can be used safely
      and effectively for corneal neovascularization resulting from different ocular
      surface disorders, providing an additional strategy to improve success of corneal
      grafts.

PMID- 22357392
TI  - Reorientation of inverted endothelial graft during Descemet stripping automated
      endothelial keratoplasty.
AB  - We describe a technique during Descemet stripping automated endothelial
      keratoplasty for reorientation of an inverted endothelial graft. This technique
      allows the inversion to be predictably corrected with minimal manipulation and
      trauma to the endothelium, thereby reducing the risk of primary failure and
      subsequent repeat of the transplant.

PMID- 22357393
TI  - Vertical and horizontal corneal epithelial thickness profiles determined by
      ultrahigh resolution optical coherence tomography.
AB  - PURPOSE: To measure vertical and horizontal thickness profiles of the central and
      peripheral corneal epithelium and determine if daytime changes occur. METHODS:
      Forty eyes of 20 normal subjects were imaged by ultrahigh resolution spectral
      domain optical coherence tomography to profile the corneal epithelial thickness
      from the edge of Bowman layer to the central cornea across the vertical and
      horizontal meridians. Measurements were made at 10:00 AM and again at 6 and 8
      hours later. RESULTS: The baseline vertical meridional epithelial thickness was
      thinnest, 42.9 +/- 4.1 MUm, at the edge of Bowman layer in the superior region.
      It increased in thickness (P < 0.01), toward the central cornea. The central
      epithelium averaged 52.5 +/- 2.4 MUm, becoming thickest, 55.2 +/- 2.5 MUm, in the
      inferior pericentral region. It thinned toward the inferior periphery, reaching
      51.3 +/- 5.1 MUm at the edge of Bowman layer (P < 0.01). Along the horizontal
      meridian, the epithelium was thickest at the nasal side, 58.6 +/- 5.1 MUm, and
      temporal side, 59.3 +/- 6.6 MUm, near the edges of Bowman layer. It thinned
      toward the central cornea. There were no significant changes in the epithelial
      thickness at any location over 8 hours. CONCLUSIONS: Epithelial thickness varied
      over the horizontal and vertical meridians and appeared stable during the
      daytime.

PMID- 22357394
TI  - Cortical control of postural balance in patients with hemiplegic stroke.
AB  - Despite its remarkable effect on the activities of daily living, the precise
      mechanism underlying balance control after stroke remains to be elucidated. In
      this study, we investigated the cortical activation induced by postural
      perturbation in 20 patients with stroke using a 50-channel event-related
      functional near-infrared spectroscopy. A combination of brisk forward and
      backward movements of a platform without any prior cue was used as an external
      postural perturbation. Multi-participant analysis of oxygenated hemoglobin
      signals showed postural perturbation-related cortical activation in the
      prefrontal cortical areas in both hemispheres as well as the premotor and
      parietal association cortical areas in the unaffected hemisphere. Regression
      analysis using the individual Berg Balance Scale as the regressor showed a
      significant positive correlation between balance ability and the postural
      perturbation-related changes in oxygenated hemoglobin signals in the
      supplementary motor areas and prefrontal cortical areas in both hemispheres.
      Consistent with the previous findings in healthy participants, these findings
      suggest that the broad cortical network, including the prefrontal, premotor,
      supplementary motor, and parietal cortical areas in both hemispheres, was
      essential for balance control even in poststroke patients.

PMID- 22357395
TI  - A neural mechanism for aesthetic experience.
AB  - Aesthetic experience associated with viewing art has been hypothesized to depend
      on both low-level sensory processing and high-level conceptual processing. To
      test these hypotheses, we used functional MRI to evaluate the magnitude of
      activity in sensory motion processing region MT+ and in the prefrontal cortex
      while participants viewed van Gogh paintings that evoked a range of motion
      experience. In support of the sensory hypothesis of aesthetic experience and the
      conceptual hypothesis of aesthetic experience, MT+ activity was correlated to the
      degree of motion experience (but not the experience of pleasantness) and activity
      in the right anterior prefrontal cortex was associated with the experience of
      pleasantness (but not motion experience). These findings provide a neural
      mechanism for aesthetic experience that depends on sensory processing and
      conceptual processing. The techniques employed in the current study will serve as
      a framework for future studies to investigate the neural basis of aesthetic
      experience associated with other visual and nonvisual art forms such as
      sculpture, architecture, or music.

PMID- 22357396
TI  - Experimental changes in bodily self-consciousness are tuned to the frequency
      sensitivity of proprioceptive fibres.
AB  - Several lines of evidence suggest an important implication of proprioceptive
      signals in bodily self-consciousness. By manipulating proprioceptive signals
      using muscle vibration, here, we investigated whether such effects depend on the
      vibration frequency by testing three different vibratory stimuli applied at the
      lower limbs (20, 40 and 80 Hz). We thus explored whether frequency-specific
      proprioceptive interference that has been reported in postural or motor tasks
      will also be found for measures of bodily self-consciousness. Self-identification
      (questionnaires) and visuotactile integration (asking participants to make
      tactile discriminations) were quantified during synchronous and asynchronous
      stroking conditions that are known to manipulate bodily self-consciousness. We
      found that even though muscle vibrations were applied at the same body location
      in all cases, 20 Hz vibrations did not alter the magnitude of self-identification
      and visuotactile integration, whereas 40 and 80 Hz vibrations did. These
      frequency-specific effects extend earlier vibration effects on motor and postural
      tasks to bodily self-consciousness. We suggest that the observed changes in
      bodily self-consciousness are due to altered proprioceptive signals from the
      lower limbs and that these changes depend on the tuning of Ia fibres to muscle
      vibration.

PMID- 22357397
TI  - Sex differences in event-related potential components during the solution of
      complex mental rotation tasks.
AB  - The objective of the study was to evaluate the factor of sex in terms of its
      influence on event-related potential components during the solution of a complex
      mental rotation task. To evaluate the factor of sex, independent of differences
      in ability levels and hormonal changes, women and men were equalized with respect
      to general intelligence and spatial ability. In addition, all women were tested
      during the low-estrogen phase of the menstrual cycle. The event-related potential
      analysis indicated that men showed shorter P3 and longer P1 latencies, as well as
      lower N1 amplitudes. These results suggest that men devoted more time to the
      analysis of irrelevant information presented in the rotation tasks, which
      resulted in mental rotation taking place earlier in men than in women. It can be
      concluded that, even though men and women showed similar performances on complex
      rotation tasks, they differed in their solution processes.

PMID- 22357398
TI  - Unmatched perception of speed when running overground and on a treadmill.
AB  - This study compared the perception of speed between overground and treadmill
      running. Twenty-one participants ran overground around an athletic track at their
      preferred speed for 3 min, immediately followed by a 3-min treadmill run and a
      further 3-min overground run. During the treadmill run, participants were blinded
      to the speed display and were free to adjust the speed until it was perceived
      similar as their previous self-selected overground speed. A video camera was used
      to determine the average running speed during each overground run. A one-way
      ANOVA with repeated measures was used to detect differences among the three
      speeds: overground speed during session 1 (OG1), perceived overground speed on
      the treadmill (TM), and overground speed during session 2 (OG2). A significant
      difference among the three running speeds was found (P=.039). Post hoc analyses
      showed that the treadmill speed was much slower than both overground speeds but
      the overground speed did not differ between session 1 and session 2 (OG1: 3.99
      (0.78) m/s, TM: 2.73 (0.62) m/s, OG2: 3.80 (0.74) m/s). These findings confirmed
      that one's perception of speed was influenced by the treadmill on which
      individuals were unable to match their corresponding self-selected overground
      running speed. The unmatched perception of speed is likely due to the distortion
      of normal visual inputs resulting from the discrepancy between observed and
      expected optic flow. Clinicians, therapists and treadmill users should be aware
      of the different psychological demands between treadmill and overground
      locomotion when selecting gait speed.

PMID- 22357400
TI  - Procalcitonin and neopterin levels do not accurately distinguish bacterial from
      viral infections in ill-returned travellers with fever.
AB  - The diagnostic performance of procalcitonin and neopterin as markers for
      bacterial and viral causes of fever was evaluated in a cohort of 69 febrile
      travellers with known etiological agents. Our aim was to establish a decision
      rule to minimize empirical antibiotic treatment. Compared with C-reactive protein
      (CRP) and leukocyte (differential) counts, procalcitonin and neopterin had a
      disappointing diagnostic accuracy. Refraining from antibiotics in case of
      combined presence of lymphocytosis and/or CRP <=10 mg/l would result in an 85%
      reduction in unwanted antibiotic treatment in patients with viral disease but in
      adequate antibiotic coverage of all patients with bacterial disease.

PMID- 22357399
TI  - Preventive Chemotherapy and Transmission Control (PCT) databank: a tool for
      planning, implementation and monitoring of integrated preventive chemotherapy for
      control of neglected tropical diseases.
AB  - The integration of vertical control programmes of neglected tropical diseases
      (NTDs) aims to contain operational cost, simplify the application of the control
      measures and further extend the coverage of interventions. The Preventive
      Chemotherapy and Transmission Control (PCT) databank was established by the WHO
      to facilitate access and sharing of information from national programmes with
      stakeholders involved in NTD control. The PCT databank contains compilations of
      historical and current information on disease-specific epidemiological
      situations, the geographical overlapping of NTDs and progress of control
      activities in all the NTD-endemic countries. A summary of country-specific
      epidemiological maps and the progress of control activities are available from
      the online PCT databank and the Country Profiles. Annual progress of preventive
      chemotherapy interventions targeting specific NTDs is reported in the Weekly
      Epidemiological Record (WER) published annually for each disease targeted. In
      this paper, the method of data collection and compilation used to establish the
      PCT databank is explained and the key features of the online PCT databank, the
      Country Profiles and WER are presented.

PMID- 22357401
TI  - Fifty years of dengue in India.
AB  - Dengue is the most important mosquito-borne, human viral disease in many tropical
      and sub-tropical areas. In India the disease has been essentially described in
      the form of case series. We reviewed the epidemiology of dengue in India to
      improve understanding of its evolution in the last 50 years and support the
      development of effective local prevention and control measures. Early outbreak
      reports showed a classic epidemic pattern of transmission with sporadic
      outbreaks, with low to moderate numbers of cases, usually localized to urban
      centres and neighbouring regions, but occasionally spreading and causing larger
      epidemics. Trends in recent decades include: larger and more frequent outbreaks;
      geographic expansion of endemic transmission; spread of the disease from urban to
      peri-urban and rural areas; an increasing proportion of severe cases and deaths;
      and progression to hyperendemicity, particularly in large urban areas. The global
      picture of dengue in India is currently that of a largely endemic country.
      Understanding demographic differences in infection rates and severity of dengue
      has important implications for the planning and implementation of effective
      public health prevention and control measures and targeting of future vaccination
      campaigns.

PMID- 22357402
TI  - Influenza vaccination coverage among pregnant women - 29 States and New York
      City, 2009-10 season.
AB  - Because influenza can be especially severe during pregnancy, the American College
      of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on
      Immunization Practices (ACIP) recommend influenza vaccination for women who will
      be pregnant during the influenza season, regardless of trimester. During the 2009
      10 influenza season, pregnant women were at increased risk for severe disease and
      mortality from influenza A (H1N1)pdm09 (pH1N1) pandemic virus infection.
      Anticipating this risk, both the inactivated trivalent seasonal and monovalent
      pH1N1 vaccinations were recommended for pregnant women. To estimate state
      specific seasonal and pH1N1 influenza vaccination coverage among pregnant women,
      CDC analyzed data from the Pregnancy Risk Assessment Monitoring System (PRAMS).
      This report provides estimates from 29 states and New York City (NYC) for women
      who had live births during September 2009-May 2010. Median state coverage was
      47.1% for seasonal and 40.4% for pH1N1 influenza vaccination. Overall, women who
      reported that a health-care provider offered them influenza vaccination or told
      them to get it during their pregnancy were more likely to be vaccinated than
      those without an offer or recommendation (prevalence ratio [PR] = 5.2 for
      seasonal, and PR = 14.4 for pH1N1). Substantial variation across areas was
      observed for prevalence of a provider offer or recommendation during pregnancy
      and for influenza vaccination. These findings highlight the need for state
      specific strategies that optimize provider involvement to increase influenza
      vaccination of pregnant women.

PMID- 22357403
TI  - Fatal exposure to methylene chloride among bathtub refinishers - United States,
      2000-2011.
AB  - In 2010, the Michigan Fatality Assessment and Control Evaluation program
      conducted an investigation into the death of a bathtub refinisher who used a
      methylene chloride-based paint stripping product marketed for use in aircraft
      maintenance. The program identified two earlier, similar deaths in Michigan.
      Program staff members notified CDC's National Institute for Occupational Safety
      and Health (NIOSH), which in turn notified the Occupational Safety and Health
      Administration (OSHA). In addition to the three deaths, OSHA identified 10 other
      bathtub refinisher fatalities associated with methylene chloride stripping agents
      that had been investigated in nine states during 2000-2011. Each death occurred
      in a residential bathroom with inadequate ventilation. Protective equipment,
      including a respirator, either was not used or was inadequate to protect against
      methylene chloride vapor, which has been recognized as potentially fatal to
      furniture strippers and factory workers but has not been reported previously as a
      cause of death among bathtub refinishers. Worker safety agencies, public health
      agencies, methylene chloride-based stripper manufacturers, and trade
      organizations should communicate the extreme hazards of using methylene chloride
      based stripping products in bathtub refinishing to employers, workers, and
      consumers. Employers should strongly consider alternative methods of bathtub
      stripping and always ensure worker safety protections that reduce the risk for
      health hazards to acceptable levels. Employers choosing to use methylene chloride
      based stripping products must comply with OSHA's standard to limit methylene
      chloride exposures to safe levels.

PMID- 22357404
TI  - Update: Influenza activity - United States, October 2, 2011-February 11, 2012.
AB  - This report summarizes U.S. influenza activity* since the beginning of the 2011
      12 influenza season (October 2, 2011) and updates the previous report. From
      October through early January, influenza activity remained low throughout the
      United States. Activity increased slightly in early February 2012, but remains
      low. Influenza A (H1N1)pdm09 (pH1N1), influenza A (H3N2), and influenza B viruses
      all have been identified thus far this influenza season, and the majority of
      viruses in circulation are antigenically similar to strains included in the 2011
      12 vaccine.

PMID- 22357405
TI  - Executive dysfunction and memory impairment in schizoaffective disorder: a
      comparison with bipolar disorder, schizophrenia and healthy controls.
AB  - BACKGROUND: Deficits in memory and executive performance are well-established
      features of bipolar disorder and schizophrenia. By contrast, data on cognitive
      impairment in schizoaffective disorder are scarce and the findings are
      conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the
      Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and
      executive function in 45 schizophrenic patients, 26 schizomanic patients and 51
      manic bipolar patients in comparison to 65 healthy controls. The patients were
      tested when acutely ill. RESULTS: All three patient groups performed
      significantly more poorly than the controls on global measures of memory and
      executive functioning, but there were no differences among the patient groups.
      There were few differences in memory and executive function subtest scores within
      the patient groups. There were no differences in any test scores between manic
      patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic,
      schizomanic and manic patients show a broadly similar degree of executive and
      memory deficits in the acute phase of illness. Our results do not support a
      categorical differentiation across different psychotic categories with regard to
      neuropsychological deficits.

PMID- 22357406
TI  - Factors associated with early catheter-related complications in peritoneal
      dialysis.
AB  - PURPOSE: It is advocated to delay the start of peritoneal dialysis (PD) at least
      10-14 days after insertion of peritoneal catheter. The aim of this study was to
      investigate factors associated with catheter-related complications (CRC) in
      patients starting PD early (1-13 days) (ES) and late (14 days or more) (LS) after
      catheter implantation. MATERIAL/METHODS: Single center, retrospective analysis of
      CRC occurring within 14 days of follow up after peritoneal dialysis initiation in
      ES and LS group of patients. RESULTS: A total of 97 patients were analyzed.
      Seventy percent of them were ES. There were significantly more CRC in ES vs. LS
      (31% vs. 3%, p=0.01). Significantly more mechanical CRC occurred in ES than in LS
      (21% vs. 0%, p=0.01). Occurrence of infectious CRC did not differ between the
      groups. In multivariate analysis the only predictor of CRC development was the
      time elapsed between catheter insertion and beginning of PD (Odds Ratio [OR] 0.80
      95% Confidence Interval [95% CI] 0.70-0.91; p=0.001). CONCLUSIONS: Each day of
      delay of PD initiation following peritoneal catheter insertion decreases the odds
      for development of mechanical CRC.

PMID- 22357407
TI  - Psychological aspects of active surveillance.
AB  - PURPOSE OF REVIEW: Active surveillance is emerging as a serious alternative to
      radical therapy for low-risk prostate cancer. In a situation in which the
      difference in effects on disease morbidity and mortality of different treatment
      options for these malignancies is likely to be small, the quality of life and
      psychological aspects may be decisive in treatment choice. RECENT FINDINGS: The
      following three are the main issues being covered in the literature on
      psychological aspects of active surveillance. First, the process of consultation
      with the physician and treatment choice in men diagnosed with low-risk prostate
      cancer. Second, the effect of active surveillance on physical domains and
      resulting anxiety and distress, and on quality of life in general. And third, the
      possible supportive and educational interventions for patients on active
      surveillance. Observations are scarce and derived from nonrandomized studies with
      a limited follow-up after diagnosis. SUMMARY: At the moment of treatment choice,
      fear of disease progression is the main reason to reject active surveillance.
      Active surveillance may spare physical domains and does not cause much anxiety or
      distress on short term in men who choose this strategy. Once men opt for active
      surveillance, only a minority of them switch to radical treatment due to
      psychological reasons. Supportive and educational interventions should be
      considered.

PMID- 22357408
TI  - Towards a dialect-neutral assessment instrument for the language skills of
      Afrikaans-speaking children: the role of socioeconomic status.
AB  - The aims of the study were to establish whether there is a correlation between
      the socioeconomic background of Afrikaans-speaking children and their performance
      on a dialect-neutral language test, and to ascertain whether the allowance the
      test currently makes for parental education level is sufficient. The Afrikaans
      version of the Diagnostic Evaluation of Language Variation (Seymour, Roeper & de
      Villiers, 2005a ) was administered to 231 Afrikaans-speaking children age 4 ; 0
      to 9 ; 11 from various socioeconomic backgrounds. A positive correlation was
      found between the composite language scores as well as the scores for each of the
      language domains (syntax, pragmatics, semantics) and the primary female
      caregivers' highest level of education. Children with father figures present did
      not outperform those without. It appears that the original manner of
      accommodating parental education level in interpreting the children's language
      scores on the test is sufficient and need not be refined for the South African
      context.

PMID- 22357409
TI  - Proper packaging for food and no-food products to avoid injuries.
AB  - OBJECTIVES: This paper aims to present data on proper packaging for food and no
      food products to avoid injuries. METHODS: Data collection was made from the Susy
      Safe data base and the results of the literature research. RESULTS: Fatal and
      near fatal foreign bodies injuries may occur at any age, however it is a
      particular problem for infants and young children due to a variety of
      predisposing factors. Safety packaging is therefore a landmark and a model for
      accident prevention. CONCLUSIONS: Taken the lack of researches and specificity on
      this subject, it is warmly suggested that a broader and deeper exploration, both
      at customer's and public health levels, has to be made, highlighting major risks
      and complications. Packaging classes are extremely composite, therefore accuracy
      in data registry must be achieved, since from a preventive point of view it is
      basilar not only knowing the nature of the foreign body but also having
      information on its origin.

PMID- 22357410
TI  - Foreign body injuries: the urgent need for updating the field.

PMID- 22357411
TI  - Identifying factors for optimal development of health-related websites: a delphi
      study among experts and potential future users.
AB  - BACKGROUND: The Internet has become a popular medium for offering tailored and
      targeted health promotion programs to the general public. However, suboptimal
      levels of program use in the target population limit the public health impact of
      these programs. Optimizing program development is considered as one of the main
      processes to increase usage rates. OBJECTIVE: To distinguish factors potentially
      related to optimal development of health-related websites by involving both
      experts and potential users. By considering and incorporating the opinions of
      experts and potential users in the development process, involvement in the
      program is expected to increase, consequently resulting in increased
      appreciation, lower levels of attrition, and higher levels of sustained use.
      METHODS: We conducted a systematic three-round Delphi study through the Internet.
      Both national and international experts (from the fields of health promotion,
      health psychology, e-communication, and technical Web design) and potential users
      were invited via email to participate. During this study an extensive list of
      factors potentially related to optimal development of health-related websites was
      identified, by focusing on factors related to layout, general and risk
      information provision, questionnaire use, additional services, and ease of use.
      Furthermore, we assessed the extent to which experts and potential users agreed
      on the importance of these factors. Differences as well as similarities among
      experts and potentials users were deduced. RESULTS: In total, 20 of 62 contacted
      experts participated in the first round (32% response rate); 60 of 200 contacted
      experts (30% response rate) and 210 potential users (95% response rate) completed
      the second-round questionnaire, and 32 of 60 contacted experts completed the
      third round (53% response rate). Results revealed important factors consented
      upon by experts and potential users (eg, ease of use, clear structure, and
      detailed health information provision), as well as differences regarding
      important factors consented upon by experts (eg, visual aids, self-monitoring
      tool, and iterative health feedback) or by potential users only (eg, bread crumb
      navigation and prevention of receiving spam). CONCLUSIONS: This study is an
      important first step in determining the agreed-upon factors that should be taken
      into account when developing online health promotion programs. The public health
      impact of these programs will be improved by optimizing the development process
      in line with these factors.

PMID- 22357413
TI  - Aliskiren and perindopril reduce the levels of transforming growth factor-beta in
      patients with non-diabetic kidney disease.
AB  - BACKGROUND: It is highly likely that the rise in plasma prorenin and plasma renin
      during renin inhibitor treatment is induced at least as much by the fall in blood
      pressure (BP) as it is by the negative feedback of angiotensin II. This could
      potentially be harmful because high levels of renin and prorenin may stimulate
      the (pro)renin receptor, thus inducing profibrotic effects. To further understand
      this relationship, the influence of aliskiren on the urinary excretion of
      transforming growth factor-beta1 (TGF-beta1) and procollagen III N-terminal
      propeptide (PIIINP) was evaluated in patients with nondiabetic kidney diseases.
      METHODS: Aliskiren 300 mg and perindopril 10 mg, were each individually
      administered for 12 weeks separated by a placebo period in a cross-over,
      randomized, double-blinded pilot study. RESULTS: A 1,131% (P < 0.001) and 628% (P
      < 0.001) increase in plasma renin concentration was observed after the aliskiren
      and perindopril therapies, respectively, as compared to the placebo. Aliskiren
      and perindopril increased prorenin concentrations as compared to the placebo by
      100% (P < 0.01) and 52.4% (P = 0.53), respectively. The TGF-beta1 excretion was
      lower after tested therapies compared to the placebo (55.0 +/- 7.56 vs. 56.21 +/-
      8.56 vs. 85.79 +/- 14.11 pg/mg creatinine; P = 0.016); without differences
      between aliskiren and perindopril. PIIINP excretion did not differ between
      treatments. CONCLUSIONS: The study shows that both aliskiren and perindopril
      suppress TGF-beta1 in patients with chronic kidney diseases. This effect was
      observed despite significant increases in the renin and prorenin concentrations.
      Further studies involving histological assessments are required to elucidate the
      exact impact of these agents on renal fibrosis.

PMID- 22357412
TI  - Associations of noninvasive measures of arterial compliance and ankle-brachial
      index: the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: The association between measures of arterial compliance and
      peripheral arterial disease (PAD) is unclear. Early changes in arterial wall
      compliance could be a useful marker of patients at high risk for developing lower
      extremity atherosclerosis. METHODS: We used linear and logistic regression models
      on baseline data from 2,803 female and 2,558 male participants in the Multi
      Ethnic Study of Atherosclerosis (MESA) to study associations between tonometry
      derived baseline measures of arterial compliance (large artery compliance (C1)
      and small artery compliance (C2)) and the baseline ankle-brachial index (ABI), as
      well as change in the ABI over ~3 years of follow-up. RESULTS: In cross-sectional
      analyses, lower C1 and C2 values, indicating poorer arterial compliance, were
      associated with lower ABI. There were significant linear trends across strata of
      ABI, especially in C2 which ranged from 3.7 ml/mm Hg * 100 (95% confidence
      interval (CI) 3.3-4.2) in women with an ABI < 0.90 to 4.2 ml/mm Hg * 100 (95% CI
      4.1-4.3 P < 0.001) in women with ABI 1.10 - <1.40. Similar significant trends (P
      < 0.001) were seen in men. In prospective analyses, those with the lowest tertile
      of C2 values at baseline had a greater multivariable-adjusted odds for decline in
      ABI of >= 0.15 over 3 years compared to those with the highest C2 values at
      baseline (odds ratio (OR) 1.80, 95% CI 1.23-2.64). CONCLUSIONS: We observed that
      less compliant arteries were significantly associated with low ABI in cross
      sectional analysis and with greater decline in odds of ABI over time.

PMID- 22357414
TI  - Sodium intake is associated with parasympathetic tone and metabolic parameters in
      mild hypertension.
AB  - BACKGROUND: Although the impairment of parasympathetic cardiac control was
      described in hypertensives submitted to a high salt diet, the impact of this
      autonomic abnormality on metabolic and inflammation markers in patients with mild
      hypertension has not been explored. METHODS: Four hundred and ninety mild
      essential hypertensive patients (144 +/- 9/94 +/- 9 mm Hg, 49.5 +/- 13.9 years,
      67.9 % male) were studied. Dietary sodium intake was estimated by measuring 24-h
      urinary sodium excretion (UNa), and the patients were classified according to UNa
      levels as follows: low (<50 mEq/l), medium (50-99 mEq/l), and high UNa (>=100
      mEq/l). Parasympathetic tone was evaluated by assessing heart rate recovery (HRR)
      after an exercise stress test. HRR, plasma lipids, glucose metabolism, and
      inflammatory biomarkers were compared across UNa groups. RESULTS: HRR and high
      density lipoprotein (HDL)-cholesterol were progressively lower, and insulin
      (INS), homeostasis model assessment of insulin resistance (HOMAir),
      ultrasensitive-C-reactive protein (usCRP) were progressively higher across
      increasing UNa groups. In the low and medium UNa groups, HDL-cholesterol was
      higher and CRP was lower than that in high UNa (P < 0.01 and P < 0.05,
      respectively) (Dunnett post-hoc test). In the low UNa group, triglycerides (TGs),
      INS, and HOMAir were lower than that in high UNa (P < 0.05). Multiple linear
      regression analysis showed that UNa, HOMAir, and heart rate (HR) were negatively
      associated with HRR (P < 0.0001, P < 0.0001, and P = 0.001, respectively).
      CONCLUSIONS: In the essential hypertensive patients studied high sodium intake is
      associated with parasympathetic inhibition, lipid disturbances, and inflammation.
      Studies designed to assess causality between sodium intake and metabolic and
      autonomic status are needed to evaluate the relevance of controlling sodium
      intake, especially in hypertensive patients.

PMID- 22357415
TI  - Prevalence, awareness, treatment, and control of hypertension among herdsmen
      living at 4,300 m in Tibet.
AB  - BACKGROUND: Studies on blood pressure (BP) in high-altitude areas are scarce and
      the results are controversial. Tibetans live in regions at high altitudes, and
      data on the prevalence of hypertension in this population is not currently well
      known. METHODS: All Tibetans aged 40 years and older living in the township of
      Yangbajing (4,300 m) in Tibet, China were invited to participate in the 2009
      survey. BP was measured with electronic sphygmomanometers (calibrated by the
      results of a previous study). Histories of hypertension and medication use were
      collected through face-to-face interviews. Hypertension was defined as systolic
      BP (SBP) >=140 mm Hg and/or diastolic BP (DBP) >=90 mm Hg, or antihypertensive
      medication use in the past 2 weeks. RESULTS: A total of 701 adults (aged 40-89,
      42.9% male, 94.9% herdsmen) were recruited. The mean (s.d.) SBP/DBP was 146.6
      (31.3)/92.0 (15.7) mm Hg and the prevalence of hypertension was 55.9%. Of note,
      61.2% of those with hypertension had stage 2 hypertension (SBP >=160 or DBP >=100
      mm Hg). At age 70 years and older, the mean (s.d.) SBP/DBP were 182.8
      (30.9)/102.6 (13.4) mm Hg. Among those with hypertension (n = 392), only 19.9%
      were aware of their condition, 2.6% were taking medication, and only one
      participant had controlled BP. CONCLUSION: According to our survey in Yangbajing,
      Tibetan adults aged 40 years and older living at high altitudes had high BP and
      prevalence of hypertension with low awareness, treatment, and control. Future
      studies are needed to clarify the association between BP, altitude, and other
      possible causes.

PMID- 22357416
TI  - Multiple-endpoint assay provides a detailed mechanistic view of responses to
      herbicide exposure in Chlamydomonas reinhardtii.
AB  - The release of herbicides into the aquatic environment raises concerns about
      potential detrimental effects on ecologically important non-target species, such
      as unicellular algae, necessitating ecotoxicological risk assessment. Algal
      toxicity tests based on growth, a commonly assessed endpoint, are integrative,
      and hence do not provide information about underlying toxic mechanisms and
      effects. This limitation may be overcome by measuring more specific biochemical
      and physiological endpoints. In the present work, we developed and applied a
      novel multiple-endpoint assay, and analyzed the effects of the herbicides
      paraquat, diuron and norflurazon, each representing a specific mechanism of toxic
      action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints
      added to assessment of growth were pigment content, maximum and effective
      photosystem II quantum yield, ATP content, esterase and oxidative activity. All
      parameters were measured at 2, 6 and 24h of exposure, except for growth and
      pigment content, which were determined after 6 and 24h only. Effective
      concentrations causing 50% of response (EC50s) and lowest observable effect
      concentrations (LOECs) were determined for all endpoints and exposure durations
      where possible. The assay provided a detailed picture of the concentration- and
      time-dependent development of effects elicited by the analyzed herbicides, thus
      improving the understanding of the underlying toxic mechanisms. Furthermore, the
      response patterns were unique to the respective herbicide and reflected the
      different mechanisms of toxicity. The comparison of the endpoint responses and
      sensitivities revealed that several physiological and biochemical parameters
      reacted earlier or stronger to disturbances than growth. Overall, the presented
      multiple-endpoint assay constitutes a promising basis for investigating stressor
      and toxicant effects in green algae.

PMID- 22357418
TI  - What is the role of accreditation in the era of competency-based specialist
      training - a perspective from the United Kingdom.
AB  - Higher specialist training in cardiology has undergone significant reform across
      numerous countries in recent years. A number of factors have driven these
      changes, from the legal requirement to reduce working hours (i.e., the European
      Working Time Directive) to the increasing sub-specialisation within cardiology
      and the need for appropriately focussed training within these sub-specialties.
      Cardiac imaging provides a neat framework in which to examine the effect of such
      changes. Technological advances in echocardiography, nuclear cardiology, computed
      tomography and magnetic resonance imaging have seen an unprecedented increase in
      the utilisation of all techniques. The need to deliver appropriate training is
      recognised and numerous accreditation schemes exist within cardiovascular
      imaging, with the aim of demonstrating that specified levels of experience and
      expertise have been attained. However, in the United Kingdom, there has been a
      change from the traditional experience-based training scheme to a new, competency
      based training program, with regular use of workplace-based assessments to prove
      competence in a specified area or procedure. As this training model is
      implemented, it will produce a generation of trainees for whom individual
      accreditation schemes carry less value, given the competency assessment
      inherently present within their new training system. This article discusses the
      role of accreditation in the era of competency-based specialist training from a
      cardiac imaging perspective using the UK experience to highlight the challenges
      facing trainees and to encourage a debate around how best to ensure cardiac
      imaging specialists are fully competent at the end of their specific training
      programs.

PMID- 22357417
TI  - Intraleaflet haemorrhage as a mechanism of rapid progression of stenosis in
      bicuspid aortic valve.
AB  - BACKGROUND: The mechanisms are unknown why aortic stenosis (AS) progresses faster
      in patients with bicuspid aortic valve (BAV) than those with tricuspid aortic
      valve (TAV). The objective of this study is to examine whether neoangiogenesis,
      haemorrhage in the aortic valve leaflet (intraleaflet haemorrhage) and macrophage
      infiltration are involved in the mechanisms of rapid progression of AS with BAV.
      METHODS: We retrospectively examined specimens of aortic valve leaflets obtained
      from patients who had undergone aortic valve replacement for AS (AS with BAV:
      n=22, AS with TAV: n=86). The stenotic valve leaflets were examined by
      immunohistochemistry to detect vascular endothelial cells, red blood cell remnant
      and macrophage. We assessed the progression of AS by annualized changes in the
      aortic valve area (DeltaAVA: cm(2)/year) which was evaluated by serial
      echocardiography with the continuity equation. RESULTS: Neoangiogenesis,
      intraleaflet haemorrhage and macrophage infiltration were frequently observed in
      leaflets obtained from AS patients with BAV (neoangiogenesis: 82%, intraleaflet
      haemorrhage: 91%, macrophage infiltration 91%). These pathological changes were
      more severe in AS with BAV than TAV, and they were positively correlated with
      progression of AS in patients with BAV. Multivariated analysis revealed that
      bicuspid anatomy was the only factor that predicted neoangiogenesis, intraleaflet
      haemorrhage and macrophage infiltration when patients with BAV and those with TAV
      were combined. CONCLUSIONS: Neoangiogenesis, intraleaflet haemorrhage and
      macrophage infiltration are more severe in leaflets from AS with BAV than TAV and
      associated with rapid progression of AS with BAV. This pathological process may
      account for rapid progression of AS with BAV.

PMID- 22357419
TI  - Uric acid: a novel prognostic marker for cardiovascular disease.

PMID- 22357420
TI  - Cinaciguat prevents neointima formation after arterial injury by decreasing
      vascular smooth muscle cell migration and proliferation.
AB  - AIMS: Vascular smooth muscle cell (VSMC) migration, proliferation and remodeling
      of the extracellular matrix contribute to lumen loss after arterial injury
      leading to restenosis. Several studies indicated the role of the cyclic guanosine
      monophosphate signaling in neointimal formation. Cinaciguat, the novel soluble
      guanylate cyclase activator, currently being in phase IIb clinical trial, has
      been shown to exert antiplatelet and anti-remodeling effects in animal models of
      vascular pathology. In this study we investigated the effects of cinaciguat on
      post-injury arterial stenosis. METHODS AND RESULTS: Male Sprague-Dawley rats
      (n=100) underwent endothelial denudation by wire injury of the right common
      carotid artery. Cinaciguat (10mg/kg/day orally) were administered to 50 rats (1-,
      2-, 3-day and 1-, 3-week treatment time), while 50 rats received placebo. A 3
      week treatment resulted in a significantly reduced vascular stenosis (17.53 +/-
      10.84% in the treatment group vs. 43.25 +/- 30.83% in the control wire injury
      group) and neointima/media area ratio (0.45 +/- 0.32 in the treatment group vs.
      1.09 +/- 0.69 in the control wire injury group). By using quantitative real-time
      PCR, Western blot and immunohistochemistry, matrix-metallopreoteinase-9 (MMP-9)
      was found to be upregulated in the control-injured carotids over the whole follow
      up, and cinaciguat significantly decreased MMP-9 expression by 3 weeks. As
      assessed by protein immunoblot, injury-induced local decrease of soluble
      guanylate cyclase beta1 subunit could be recovered by cinaciguat. In vitro wound
      healing assay with VSMCs revealed dose-dependent antimigratory and
      antiproliferative effects of cinaciguat. Plasma level of cyclic guanosine
      monophosphate was significantly elevated after 3 weeks of treatment. CONCLUSION:
      Our results show that cinaciguat prevents injury-induced neointimal hyperplasia
      by decreasing VSMC migration and proliferation through the regulation of MMP-9.

PMID- 22357421
TI  - Ventricular fibrillation risk factors in over one thousand patients with
      accessory pathways.
AB  - BACKGROUND: Published data concerning risk factors of VF in WPW patients are
      inconsistent or contradictory. METHODS AND RESULTS: We included 1007 patient
      (pts) (mean age 35 years; 45% female) with an accessory pathway (AP) referred for
      non pharmacological treatment. Group 1 consisted of 56 pts (42M, aged 34 +/- 15
      yrs) with an AP and documented VF and Group 2-951 pts (513M, aged 35 +/- 15 yrs)
      with an AP and without VF. Univariate predictors of VF were: overt pre
      excitation, male gender, multiple AP, large AP. Multivariate predictors were:
      overt pre-excitation, male gender and MAP. The mean shortest pre-excited RR
      interval during AF was significantly shorter in Group 1: 205 +/- 27 vs. 243 +/-
      64, P=0.019. VF as an end point of the first arrhythmia episode (AVRT or AF) was
      observed in 20 pts (15M, 5F). Primary VF (no documented arrhythmia prior to
      aborted SCD) occurred in 16 pts (13M, 3F). The mean age of primary VF pts was
      significantly lower than of pts with history of AVRT or AVRT and/or AF (24.5 vs.
      36.5 vs. 38 yrs., P<0.005 and P=0.002, respectively). Age at VF occurrence shows
      a bi-modal distribution with peak occurrences in the 2-nd/3-rd and 5-th decades.
      CONCLUSION: In patients with an accessory pathway, overt pre-excitation, male
      gender and multiple AP constitute independent risk factors of VF episodes. Young
      patients in the 2-nd/3-rd and older patients in the 5-th decade might be at
      higher risk of VF occurrence.

PMID- 22357422
TI  - The elusive mechanisms of B-type natriuretic peptides rise after ventricular
      fibrillation.

PMID- 22357423
TI  - Atherosclerotic cardiovascular disease in Egyptian women: 1570 BCE-2011 CE.
AB  - BACKGROUND: Atherosclerotic cardiovascular disease is often thought of as a
      disease of modernity, a disease affecting primarily men and a disease primarily
      affecting members of affluent Western societies. METHODS: We reviewed CT scans
      for evidence of vascular calcification as a manifestation of atherosclerosis in
      ancient Egyptian female mummies and compared the results to clinical features of
      contemporary Egyptian women, who are suffering from an epidemic of
      atherosclerotic cardiovascular disease. RESULTS: The common assumption that
      atherosclerosis is strictly a modern disease which spares women, mainly affecting
      men, is not true. We report the CT examination of an ancient Egyptian woman who
      lived more than 3000 years ago, finding calcified atherosclerotic plaque in her
      systemic arteries and other abnormalities probably due to prior myocardial
      infarction. We also confirmed recent reports of a virtual epidemic of
      atherosclerotic cardiovascular disease in contemporary Egyptian women.
      CONCLUSIONS: Atherosclerosis, both ancient and contemporary, is common in women
      as well as in men, and is related to both a genetic predisposition and to
      environmental factors including diet, exercise, obesity and exposure to smoke and
      other toxins.

PMID- 22357424
TI  - Extracellular and intracellular proteases in cardiac dysfunction due to ischemia
      reperfusion injury.
AB  - Various procedures such as angioplasty, thrombolytic therapy, coronary bypass
      surgery, and cardiac transplantation are invariably associated with ischemia
      reperfusion (I/R) injury. Impaired recovery of cardiac function due to I/R injury
      is considered to be a consequence of the occurrence of both oxidative stress and
      intracellular Ca(2+)-overload in the myocardium. These changes in the ischemic
      myocardium appear to activate both extracellular and intracellular proteases
      which are responsible for the cleavage of extracellular matrix and subcellular
      structures involved in the maintenance of cardiac function. It is thus intended
      to discuss the actions of I/R injury on several proteases, with a focus on
      calpain, matrix metalloproteinases, and cathepsins as well as their role in
      inducing alterations both inside and outside the cardiomyocytes. In addition,
      modifications of subcellular organelles such as myofibrils, sarcoplasmic
      reticulum and sarcolemma as well as extracellular matrix, and the potential
      regulatory effects of endogenous inhibitors on protease activities are
      identified. Both extracellular and intracellular proteolytic activities appear to
      be imperative in determining the true extent of I/R injury and their inhibition
      seems to be of critical importance for improving the recovery of cardiac
      function. Thus, both extracellular and intracellular proteases may serve as
      potential targets for the development of cardioprotective interventions for
      reducing damage to the heart and retarding the development of contractile
      dysfunction caused by I/R injury.

PMID- 22357425
TI  - Bivalirudin has its own shelf in the cath lab, eventually.

PMID- 22357426
TI  - Troponin leak in heart failure: moving forward to arrest cardiomyocyte attrition
      and promote myocardial regeneration.

PMID- 22357427
TI  - Arterial switch repair to transposition of great arteries: so far so good.

PMID- 22357428
TI  - Avicenna (Ibn Sina) aspect of atherosclerosis.

PMID- 22357429
TI  - Surgery in chronic pancreatitis.

PMID- 22357430
TI  - Three-trocar laparoscopic cholecystectomy in patient with situs viscerum inversus
      totalis: case report and review of the literature.
AB  - Situs viscerum inversus totalis is a rare defect with a genetic predisposition,
      which can present difficulties in the management of abdominal pathology,
      especially in laparoscopic surgery (mirror-image anatomy). We report the case of
      a 52-year-old female with situs viscerum inversus totalis, known from pediatric
      age, with a medical history of colic pain in the epigastrium radiating to the
      right abdominal quadrant. Laparoscopic cholecistectomy was safely performed with
      a three trocar technique. To the best of our knowledge this is the first time
      that laparoscopic cholecistectomy by three trocars was performed in a patient
      with situs viscerum inversus. We also review the relevant literature concerning
      this issue.

PMID- 22357431
TI  - The Hall-Findlay mammaplasty pattern for skin-sparing mastectomy: case report.
AB  - We present an application of the Hall-Findlay mammaplasty skin pattern for skin
      sparing mastectomy (SSM). This is a simplified vertical reduction mammaplasty.
      Vertical reduction mammaplasty is the procedure advised for patients with
      moderator or large ptotic breasts, who wish to have a simultaneous contra-lateral
      breast reduction/mastopexy at the time of SSM for cancer or prophylactic
      mastectomy. It is particularly suitable for breast reconstruction with autologous
      tissue in the form of free transverse rectus abdominis myocutaneous (TRAM), deep
      inferior epigastric artery perforator (DIEP) and extended latissimus dorsi (ELD)
      flaps.

PMID- 22357432
TI  - Surgical management of symptomatic simple hepatic cysts.
AB  - The authors present three cases of symptomatic, large, benign, nonparasitic
      hepatic cysts. The diagnosis was determined by US and CT scan, the latter
      enabling differential diagnosis with neoplastic or hydatid cysts. All patients
      were treated with open hepatic resection. In 2 cases, laparoscopy was performed
      to enable complete diagnosis. The authors used LigaSureTM (Covidien, USA)
      instrument, avoiding bleeding complications and reducing surgery time.
      Histological examination confirmed the diagnosis of benign cysts. CT follow-up at
      6 months and 1 year demonstrated the efficacy of the surgery, with no
      recurrences.

PMID- 22357433
TI  - Lymphoepithelioma-like gastric carcinoma presenting as giant ulcer of the lesser
      curvature: case report.
AB  - Lymphoepithelioma-like gastric carcinoma (LELGC) has special clinicopathologic
      features that differentiate it from the common gastric adenocarcinoma. LELGC is a
      rare neoplasm of the stomach with an incidence of 1-4% of all gastric cancers and
      is characterized by desmoplastic stroma uniformaly infiltrated by abundant
      lymphocytes and plasma cells. LELGC is closely associated with the Epstein-Barr
      virus (EBV), with 80-100% of LELGC being EBV-positive. LELGC has a male
      predominance, occurs in elderly people and is usually located in the upper and
      middle portion of the stomach. We report a rare case of lymphoepithelioma-like
      gastric carcinoma located in the lesser curvature at the border of the gastric
      body to the pyloric antrum.

PMID- 22357434
TI  - A time bomb in the thorax: the giant ascending aortic aneurysm: case report.
AB  - We report the case of a 82-year-old woman, asymptomatic, subject to chest
      computed tomography for trauma. Then the patient underwent surgery. Before
      sternotomy, femoro-femoral bypass was starter in order to decompress the
      aneurysm; using deep hypothermia and circulatory arrest, ascending aorta and
      hemiarch replacement were performed with a Dacron graft. Post-operative course
      was uneventful.

PMID- 22357435
TI  - Retrocaval mass in patient with von Recklinghausen disease: case report.
AB  - Type I Neurofibromatosis (NF1) is an autosomal-dominant inheritable disorder,
      with an incidence of 1:3,000, and a prevalence of 1:4,000 to 5,000. Pathogenesis
      is based on mutations of the NF1 gene, a tumor suppressor gene encoding a
      cytoplasmic protein named neurofibromin that controls cellular proliferation.
      Patients affected by NF1 typically present with cutaneous neurofibromas, cafe au
      lait spots and eye involvement, but they can also be affected by various visceral
      tumors, such as neurofibromas (nodular or plexiform type), gastrointestinal
      stromal tumors or endocrine tumors, such as pheochromocytomas. Visceral
      neurofibromas are often asymptomatic but when growing in size they may present
      with pain, palpable abdominal mass, symptoms secondary to bowel obstruction or
      main vessels compression, and even gastrointestinal bleeding when mucosa or
      submucosa are involved. In these cases surgery becomes mandatory in order to
      remove all neoplastic tissue. The Authors describe a case of a young man affected
      by NF1 with associated retrocaval abdominal mass with compression and
      displacement of the inferior vena cava, thus requiring a complex surgical
      procedure.

PMID- 22357436
TI  - Serous cystadenofibroma of the fallopian tube: case report and literature review.
AB  - INTRODUCTION: Cystadenofibromas of the Fallopian tube are very rare benign tumors
      of the female genital tract. These tumours are usually asymptomatic and are found
      incidentally. CASE REPORT: We describe a Fallopian serous cystadenofibroma in a
      50 year-old woman operated for uterine leiomyoma. The histopathologic finding
      revealed a cystic lesion connected to the salpinx. The cyst was composed of
      connective stroma lined by epithelial cuboidal cells, without pleomorfism or
      detectable mitoses. Pseudopapillary structures were observed in the lumen of the
      cyst. The patient is well on follow-up. CONCLUSION: The origin of serous
      cystadenofibroma of the Fallopian tube is not clear. The tumor is considered an
      embryologic remnant rather than a proliferating neoplastic process. These tumours
      seem to have a benign course and a malignant potential has not been described.

PMID- 22357437
TI  - Masson's tumor: a soft tissue tumor simulating a tendon cyst: case report.
AB  - INTRODUCTION: Intravascular papillary endothelial hyperplasia (Masson's
      hemangioma or Masson's tumor) is a benign vascular disease with an exuberant
      endothelial proliferation in normal blood vessels. Although relatively uncommon,
      its correct diagnosis is important because it can clinically be like both benign
      lesions and malignant neoplasms. We present a case of intravascular proliferative
      endothelial hyperplasia simulating a tendon cyst both clinically and on
      ultrasound. CASE REPORT: A 74-year old Caucasian female presented with a 4-month
      history of soreness and swelling in the fourth finger of the right hand.
      Ultrasound showed an oval mass with fluid content, referred to a tendon cyst. A
      wide surgical excision was subsequently performed. The final histological
      diagnosis was Masson's tumor. DISCUSSION: The pathogenesis of intravascular
      papillary endothelial hyperplasia is still unclear but the exuberant endothelial
      cell proliferation might be stimulated by an autocrine loop of endothelial basic
      fibroblast growth factor (bFGF) secretion. There are three types of papillary
      endothelial hyperplasia: primary, or intravascular; secondary, or mixed; and
      extravascular. The main differential diagnosis is against pyogenic granuloma,
      Kaposi sarcoma, hemangioma, and angiosarcoma. CONCLUSIONS: Masson's tumor can be
      like both benign lesions and malignant neoplasms clinically and on ultrasound.
      For this reason, the right diagnosis can be made only by histology, which reveals
      a papillary growth composed of hyperplastic endothelial cells supported by
      delicate fibrous stalks entirely confined within the vascular lumen.

PMID- 22357438
TI  - Laparoscopic surgery in acute small bowel obstruction: our experience.
AB  - Small bowel obstruction (SBO) is a very common condition, in the vast majority of
      cases caused by post-operative adhesions. It often requires surgical treatment.
      Traditionally, this consisted of a laparotomy, but nowadays a laparoscopic
      approach is also possible. This study discusses 24 cases of SBO and compares them
      with literature data. Successful complete laparoscopic treatment was feasible in
      9 patients, while conversion to laparoscopically-assisted surgery or laparotomy
      was required for the others.

PMID- 22357439
TI  - Carcinoma of unknown primary (CUP); some considerations about pathogenesis and
      diagnostic strategy, particularly focusing on CUPS pertaining to the Urology.
AB  - The term "carcinoma of unknown primary" (CUP) defines a malignant condition in
      which a metastatic cancer is documented in absence of a detectable primary site.
      It occurs in about 2/6 % of cancer patients, according to various literature
      reports. The primary tumor site results indefinable because of several either
      single or associated factors, even remaining occult at autopsy in 15/25% of CUP
      patients. The metastatic spread pattern of CUP is quite unlike that expected for
      analogous known primary malignancy. For instance, the unknown prostate cancer
      often metastasizes to the lungs and liver while the its known analogous usually
      spreads to the bone. Whether certain genetic abnormalities might play a role in
      determining a CUP condition, it remains undefined. Most CUP are adenocarcinoma,
      squamous cell carcinoma, either undifferentiated or differentiated carcinoma,
      whereas less frequently may be sarcoma, melanoma or neuroendocrine tumor. As CUP
      diagnostic management is concerned, two opposite approach modalities may be
      adopted, one, named "shotgun modality", consisting in a multiplicity of
      examinations aimed at achieving the identification of the primary tumor and the
      other, a nihilistic modality, by adopting tout court a palliative therapy of the
      metastatic disease. A reasonable intermediate diagnostic strategy consists in
      undertaking some procedures with a specific target and low cost/benefit ratio.
      Selected imaging studies, serum tumor markers, immunohistochemical analyses and
      genetic- molecular examinations on biopsy material allow sometimes to reach the
      detection of primary malignancies that might be responsive to a potential
      treatments. Nevertheless, in spite of recent sophisticated -laboratory and
      imaging progress, CUP remains a strong challenge in clinical oncology.

PMID- 22357440
TI  - Diagnostic value of PET/CT is similar to that of conventional MRI and even better
      for detecting small peritoneal implants in patients with recurrent ovarian
      cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic value of 2
      (fluorine-18)-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT in comparison with MRI
      for the detection of recurrent ovarian cancer. METHODS: Forty-seven patients with
      suspected ovarian cancer recurrence after total ablative or cytoreductive
      surgery, as well as neoadjuvant or adjuvant chemotherapy, who had undergone (18)F
      FDG PET/CT imaging were recruited for the present study. All patients also
      underwent MRI within a month of (18)F-FDG PET/CT for the same purpose. Recurrent
      cancer in the abdomen and pelvis was evaluated in each of the 47 patients and
      classified as either distant metastasis or local pelvic recurrence involving the
      vaginal stump, peritoneal implants, supradiaphragmatic region, and/or abdominal
      and pelvic lymph nodes. Special attention was paid to peritoneal implants. These
      were divided into five groups according to size of the implants: less than 0.5 cm
      (group 1), 0.5-1 cm (group 2), 1-2 cm (group 3), 2-3 cm (group 4), and larger
      than 3 cm (group 5). PET/CT findings were compared with abdominopelvic MR
      findings. Statistical analysis was carried out using the Wilcoxon signed rank
      test. RESULTS: Thirty-nine of 47 patients were found to have recurrent ovarian
      cancer. Both PET/CT and MRI were negative for recurrence in six patients. Overall
      sensitivity, specificity, positive predictive value, negative predictive value,
      and diagnostic accuracy of PET/CT were 97.5, 100, 100, 87.5, and 97.8%,
      respectively, whereas those of MRI were 95, 85.7, 97.4, 75, and 93.6%,
      respectively. For the peritoneal implants in groups 2 and 3, the sensitivity,
      negative predictive value, and diagnostic accuracy values of PET/CT were
      significantly better than those of MRI (P<0.05). CONCLUSION: The present study
      revealed that PET/CT is similar to conventional MRI for the detection of
      recurrent ovarian cancer. PET/CT has greater accuracy in the detection of small
      to-medium-sized (<2 cm) peritoneal implants compared with MRI. This may affect
      surgical decision making.

PMID- 22357441
TI  - alpha-Defensins and outcome in patients with chronic heart failure.
AB  - AIM: alpha-Defensins are part of the innate immune system. Low-grade inflammation
      seems to play a crucial role in development and progression of chronic heart
      failure (CHF). The aims of the present study were to compare plasma levels of
      alpha-defensins in CHF patients and healthy controls and to examine the
      predictive ability of alpha-defensins, alone and combined with N-terminal pro
      brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality.
      METHODS AND RESULTS: In a prospective observational study lasting 2.6 years we
      examined the prognostic value of plasma alpha-defensins with respect to mortality
      in 194 CHF patients, and compared plasma levels with those of 98 age-matched
      healthy controls. alpha-Defensin levels were twice as high among CHF patients in
      New York Heart Association (NYHA) functional class III-IV than in patients in
      NYHA class I-II and healthy controls (P = 0.001). The absolute increase in risk
      of mortality for patients with alpha-defensin levels in the upper tertile vs. the
      lowest tertile was 30% (P = 0.002). After adjusting for potential confounders
      including NT-proBNP, plasma alpha-defensins remained independently associated
      with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence
      interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural
      logarithm)-transformed alpha-defensin values. The combination of high alpha
      defensins and NT-proBNP levels provided incremental prognostic information
      independent of well-known prognostic biomarkers in heart failure. CONCLUSION:
      Plasma alpha-defensins appear to have prognostic information regarding mortality
      among patients with CHF and seem to provide incremental information to
      established clinical risk markers.

PMID- 22357442
TI  - Phase II trial of galiximab (anti-CD80 monoclonal antibody) plus rituximab (CALGB
      50402): Follicular Lymphoma International Prognostic Index (FLIPI) score is
      predictive of upfront immunotherapy responsiveness.
AB  - BACKGROUND: This phase II CALGB trial evaluated the activity and safety of an
      extended induction schedule of galiximab (G) plus rituximab (R) in untreated
      follicular lymphoma (FL). PATIENTS AND METHODS: Patients with previously
      untreated FL (grades 1, 2, 3a) received 4 weekly infusions of G + R, followed by
      an additional dose every 2 months four times. International Workshop Response
      Criteria were used to evaluate response. RESULTS: Sixty-one patients were treated
      and antibody infusions were well tolerated. The overall response rate (ORR) is
      72.1% (95% confidence interval 59.2% to 82.9%): 47.6% complete response
      (CR)/unconfirmed complete response (CRu) and 24.6% partial response. At a median
      follow-up time of 4.3 years (range, 0.3-5.3 years) median progression-free
      survival (PFS) is 2.9 years. Notably, Follicular Lymphoma International
      Prognostic Index (FLIPI) correlated with ORR, CR rate, and PFS, and the low-risk
      FLIPI group (n = 12) achieved a 92% ORR, 75% CR/CRu rate, and 75% 3-year PFS.
      CONCLUSIONS: An extended induction schedule of G + R in previously untreated FL
      is well tolerated and appears particularly efficacious in those patients with low
      risk FLIPI scores. In addition, this trial served as the initial platform for
      additional CALGB 'doublet' combination regimes of rituximab plus other novel
      targeted agents.

PMID- 22357443
TI  - Elevated serum antibodies against insulin-like growth factor-binding protein-2
      allow detecting early-stage cancers: evidences from glioma and colorectal
      carcinoma studies.
AB  - BACKGROUND: Tumor-specific immunity of insulin-like growth factor-binding protein
      2 (IGFBP-2) has been reported in several cancers. We aimed to assess the role of
      serum IGFBP-2 antibodies (IGFBP-2 Abs) in early cancer detection. PATIENTS AND
      METHODS: Glioma and colorectal carcinoma (CRC) were used as models. Serum IGFBP-2
      and IGFBP-2 Abs were measured in 260 tumor patients (145 gliomas, 45 colorectal
      polyps, and 70 CRCs) and 141 controls. Receiver operating characteristic curves
      were applied. RESULTS: Serum IGFBP-2 Ab levels were significantly elevated in
      tumors (mean: 82 ng/ml, median: 17 ng/ml, range: 0-1387 ng/ml) compared with
      controls (11, 0, 0-212 ng/ml) (P < 0.0001) and higher in early than advanced
      cancers opposite of serum IGFBP-2 levels. IGFBP-2 Abs effectively discriminated
      between controls and grade II and III gliomas [area under the curve (AUC): 0.821
      0.864; 95% confidence interval (CI) = 0.762-0.936; P < 0.0001], and CRC I-II
      (AUC: 0.668; 95% CI = 0.566-0.770; P = 0.002) as well as indicative of advanced
      polyps at high risk of CRC (AUC: 0.72; 95% CI = 0.630-0.811; P < 0.0001). The
      sensitivity and specificity for diagnosing grade II-III gliomas reached 66%-84%
      and 81%. Combined serum IGFBP-2 and IGFBP-2 Abs augmented the discriminative
      power of all stage tumors (AUC: 0.823), gliomas (AUC: 0.800), and CRCs (AUC =
      0.917). CONCLUSION: Our results first demonstrate IGFBP-2 Abs for early cancer
      detection and in combination of serum IGFBP-2 for improved cancer diagnosis.

PMID- 22357444
TI  - Alcohol drinking and non-Hodgkin lymphoma risk: a systematic review and a meta
      analysis.
AB  - BACKGROUND: Whether an association between alcohol drinking and non-Hodgkin
      lymphoma (NHL) risk exists is an open question. In order to provide
      quantification of the issue, we carried out a meta-analysis of published data.
      METHODS: We identified 21 case-control and 8 cohort studies, including a total of
      18,759 NHL cases. We derived meta-analytic estimates using random-effects models,
      taking into account correlation between estimates. RESULTS: The overall relative
      risk (RR) of NHL for drinkers versus non-drinkers was 0.85 [95% confidence
      interval (CI) 0.79-0.91]. Compared with non-drinkers, the pooled RRs were 0.88
      for light (<=1 drink per day), 0.87 for moderate (1 to <4 drinks per day), and
      0.84 for heavy (>=4 drinks per day) alcohol drinking. There was no association
      for light drinkers in cohort studies, whereas for moderate and heavy drinkers,
      the RRs were similar in case-control (0.85 for moderate, 0.92 for heavy) and
      cohort (0.89 for moderate, 0.79 for heavy) studies. The inverse relation with
      alcohol consumption (drinkers versus non-drinkers) was similar in men (RR = 0.83)
      and women (RR = 0.86), but apparently stronger in studies from Asia (RR = 0.69)
      than other world areas (RR = 0.88). CONCLUSION: This meta-analysis provides
      quantitative evidence of a favourable role of alcohol drinking on NHL risk,
      though the lack of a biological explanation suggests caution in the
      interpretation of results.

PMID- 22357445
TI  - Bone matters in lung cancer.
AB  - BACKGROUND: Bone metastases are a significant and undertreated clinical problem
      in patients with advanced lung cancer. DESIGN: We reviewed the incidence of bone
      metastases and skeletal-related events (SREs) in patients with lung cancer and
      examined the burden on patients' lives and on health care systems. Available
      therapies to improve survival and lessen the impact of SREs on quality of life
      (QoL) were also investigated. RESULTS: Bone metastases are common in lung cancer;
      however, owing to short survival times, data on the incidences of SREs are
      limited. As with other cancers, the costs associated with treating SREs in lung
      cancer are substantial. Bisphosphonates reduce the frequency of SREs and improve
      measures of pain and QoL in patients with lung cancer; however, nephrotoxicity is
      a common complication of therapy. Denosumab, a recently approved bone-targeted
      therapy, is superior to zoledronic acid in increasing the time to first on-study
      SRE in patients with solid tumours, including lung cancer. Additional roles of
      bone-targeted therapies beyond the prevention of SREs are under investigation.
      CONCLUSIONS: With increasing awareness of the consequences of SREs, bone-targeted
      therapies may play a greater role in the management of patients with lung cancer,
      with the aim of delaying disease progression and preserving QoL.

PMID- 22357446
TI  - Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy
      for unresectable locally advanced adenocarcinoma of the lung: a multicenter
      feasibility study (JCOG 0402).
AB  - BACKGROUND: We conducted a feasibility study of induction chemotherapy followed
      by gefitinib and thoracic radiotherapy (TRT) for unresectable locally advanced
      adenocarcinoma of the lung. PATIENTS AND METHODS: Patients received induction
      chemotherapy with cisplatin (80 mg/m(2), days 1 and 22) and vinorelbine (25
      mg/m(2), days 1, 8, 22, and 29) followed by gefitinib (250 mg daily, beginning on
      day 43, for 1 year) and TRT (60 Gy/30 fractions, days 57-98). The primary end
      point was feasibility, which was defined as the proportion of patients who
      completed 60 Gy of TRT and received >75% of the planned dose of gefitinib without
      developing grade 2 or worse pneumonitis. RESULTS: Of the 38 enrolled patients, 23
      patients [60.5% ; 80% confidence interval (CI) 48.8-71.3] completed treatment
      without experiencing grade 2 or worse pneumonitis. During the chemoradiation
      phase, grade 3-4 alanine aminotransferase elevations were observed in 37.1% of
      the patients. The overall response rate was 73.0% . The median survival time was
      28.5 months (95% CI 22.5-38.2), and the 2-year survival rate was 65.4% .
      CONCLUSIONS: Although the results did not meet our criterion for feasibility, the
      toxicity was acceptable. This treatment warrants further evaluation among
      patients with locally advanced non-small-cell lung cancer harboring epidermal
      growth factor receptor mutations.

PMID- 22357447
TI  - Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral
      phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced
      solid tumors.
AB  - BACKGROUND: This phase I dose-escalation study investigated the maximum tolerated
      dose (MTD), safety, pharmacokinetics, pharmacodynamics (PDs), and preliminary
      antitumor activity of BGT226, a potent, oral dual phosphatidylinositol-3-kinase
      (PI3K)/mammalian target of rapamycin inhibitor. PATIENTS AND METHODS: Fifty-seven
      patients with advanced solid tumors received BGT226 2.5-125 mg/day three times
      weekly (TIW). Dose escalation was guided by an adaptive Bayesian logistic
      regression model with overdose control. Assessments included response per RECIST,
      [18F]-fluorodeoxyglucose uptake, and phosphorylated-S6 in skin and paired tumor
      samples. RESULTS: Three patients (125 mg cohort) had dose-limiting toxic effects
      (grade 3 nausea/vomiting, diarrhea). BGT226-related adverse events included
      nausea (68%), diarrhea (61%), vomiting (49%), and fatigue (19%). BGT226
      demonstrated rapid absorption, variable systemic exposure, and a median half-life
      of 6-9 h. Seventeen patients (30%) had stable disease (SD) as best response. Nine
      patients had SD for >=16 weeks. Thirty patients (53%) achieved stable metabolic
      disease as assessed by [18F]-fluorodeoxyglucose-positron emission tomography;
      however, no correlation between metabolic response and tumor shrinkage according
      to computed tomography was observed. PD changes suggested PI3K pathway inhibition
      but were inconsistent. CONCLUSIONS: The MTD of BGT226 was 125 mg/day TIW, and the
      clinically recommended dose was 100 mg/day TIW. Limited preliminary antitumor
      activity and inconsistent target inhibition were observed, potentially due to low
      systemic exposure.

PMID- 22357448
TI  - eHealth literacy: extending the digital divide to the realm of health
      information.
AB  - BACKGROUND: eHealth literacy is defined as the ability of people to use emerging
      information and communications technologies to improve or enable health and
      health care. OBJECTIVE: The goal of this study was to explore whether literacy
      disparities are diminished or enhanced in the search for health information on
      the Internet. The study focused on (1) traditional digital divide variables, such
      as sociodemographic characteristics, digital access, and digital literacy, (2)
      information search processes, and (3) the outcomes of Internet use for health
      information purposes. METHODS: We used a countrywide representative random
      digital-dial telephone household survey of the Israeli adult population (18 years
      and older, N = 4286). We measured eHealth literacy; Internet access; digital
      literacy; sociodemographic factors; perceived health; presence of chronic
      diseases; as well as health information sources, content, search strategies, and
      evaluation criteria used by consumers. RESULTS: Respondents who were highly
      eHealth literate tended to be younger and more educated than their less eHealth
      literate counterparts. They were also more active consumers of all types of
      information on the Internet, used more search strategies, and scrutinized
      information more carefully than did the less eHealth-literate respondents.
      Finally, respondents who were highly eHealth literate gained more positive
      outcomes from the information search in terms of cognitive, instrumental (self
      management of health care needs, health behaviors, and better use of health
      insurance), and interpersonal (interacting with their physician) gains.
      CONCLUSIONS: The present study documented differences between respondents high
      and low in eHealth literacy in terms of background attributes, information
      consumption, and outcomes of the information search. The association of eHealth
      literacy with background attributes indicates that the Internet reinforces
      existing social differences. The more comprehensive and sophisticated use of the
      Internet and the subsequent increased gains among the high eHealth literate
      create new inequalities in the domain of digital health information. There is a
      need to educate at-risk and needy groups (eg, chronically ill) and to design
      technology in a mode befitting more consumers.

PMID- 22357449
TI  - Role of Toll-like receptors in primary Sjogren's syndrome with a special emphasis
      on B-cell maturation within exocrine tissues.
AB  - Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ),
      all naive mature B lymphocytes need tonic signaling to stay alive. We reasoned
      that the same holds true for those B lymphocytes that proliferate in the salivary
      glands (SGs) of patients with primary Sjogren's syndrome. Based on B cell
      infiltration, 11 SGs and three tonsil samples were selected for further
      examination. Tissue sections were stained using CD20 combined with CD10, CD21,
      CD27, CD38 or IgD. They were also laser-microdissected for quantitative RT-PCR of
      transcription factors, GC-specific activation-induced cytidine deaminase (AID)
      and TLR9. Some B cell aggregates proved to be real GCs according to their
      membrane markers, whereas others were clusters of transitional type II B cells.
      These contained mRNAs for Notch-2 and Blimp-1, but not for Pax-5, Bcl-6 and AID.
      Unanticipated was the finding of mRNAs for TLR9 in these clusters of MZ B-cells,
      but not in the real GCs. Not only do TLR9 deliver sufficiency of tonic signaling
      to keep B cells alive, but they also confer autoreactive B cells with an MZ-like
      phenotype. Thus, TLRs might be targets for forthcoming biotherapies.

PMID- 22357453
TI  - Editorial: Board recognition and introduction.

PMID- 22357454
TI  - Lapatinib-induced liver injury characterized by class II HLA and Gilbert's
      syndrome genotypes.
AB  - Lapatinib is a clinically important component of the treatment for HER2-positive
      metastatic breast cancer and has an acceptable safety profile. Lapatinib
      associated Hy's Law cases have been characterized using human leukocyte antigen
      (HLA) DQA1*02:01/DRB1*07:01 and Gilbert's syndrome UGT1A1*28/*28 genotypes. The
      HLA-positive cases had higher alanine aminotransferase (ALT) elevation, whereas
      the HLA-negative cases had a higher incidence of Gilbert's syndrome. The findings
      of our study, which extend this HLA association to lapatinib-associated serious
      liver injury, emphasize the importance of Gilbert's syndrome in the
      interpretation of Hy's Law and may lead to methods for enhancing patient safety.

PMID- 22357455
TI  - Current understanding of rheumatoid arthritis therapy.
AB  - Progress in understanding the cellular and molecular mechanisms of rheumatoid
      arthritis (RA), together with the availability of new therapies, has changed the
      way we think about RA. The paradigm shift in RA therapy has been from controlling
      symptoms to controlling the disease process with the abrogation of inflammation.
      Challenges that are still unresolved include the issues in disease prevention,
      treatment specificity to restore tolerance, approaches to facilitate tissue
      repair, and treatment optimization to fit the individual patient's disease
      phenotype and comorbidity context. This review summarizes the pathogenesis
      related rationales for the current therapeutic strategies in RA and for emerging
      therapies and potential approaches to restoring immune tolerance in RA.

PMID- 22357456
TI  - Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics
      based dosing paradigms.
AB  - Crohn's disease and ulcerative colitis are chronic inflammatory disorders
      resulting from immune dysregulation. Patients who fail conventional medical
      therapy require biological treatment with monoclonal antibodies (mAbs). Although
      mAbs are highly effective for induction and maintenance of clinical remission,
      not all patients respond, and a high proportion of patients lose response over
      time. One factor associated with loss of response is immunogenicity, whereby the
      production of antidrug antibodies accelerates mAb clearance. However, other
      factors related to patient and disease characteristics also influence the
      pharmacokinetics of mAbs. These factors include gender, body size, concomitant
      use of immunosuppressive agents, disease type, serum albumin concentration, and
      the degree of systemic inflammation. Because it is important to maintain
      clinically effective concentrations to provide optimal clinical response and drug
      exposure is affected by patient factors, a better understanding of the
      pharmacology of mAbs will ultimately result in better patient care.

PMID- 22357457
TI  - Evolution of an endovenous laser ablation practice for varicose veins.
AB  - OBJECTIVE: We aimed to assess the evolution of an endovenous laser ablation
      (EVLA) practice in the management of varicose veins in a university teaching
      hospital vascular surgical unit, over five years. METHODS: This was a
      retrospective review of a prospectively collected database of patients undergoing
      EVLA for great saphenous vein incompetence and followed up for a year. For inter-
      and intragroup comparison, patients were divided into three groups: group A:
      endovenous access generally established at the perigenicular level (n = 105);
      group B: when practice changed to gain access at lowest point of demonstrable
      reflux (n = 70); and group C: when tumescence delivery changed from manual
      injections to delivery via peristaltic pump (n = 49). Outcomes including pain
      scores, time taken to return to normal functioning, quality of life (QoL), venous
      clinical severity scores (VCSS) and complication rates were evaluated. RESULTS:
      Intergroup analysis: increase in the length of vein treated and laser density
      delivered was observed over time, even as median procedure duration decreased (P
      < 0.001). An increase in sensory disturbance was noticed in group C (P = 0.047)
      while better Aberdeen Varicose Vein Questionnaire (AVVQ) (P = 0.004), SF-36((r))
      physical domains (P < 0.05) and patient satisfaction with treatment (P = 0.025)
      were recorded in the same group at 52 weeks. No significant difference was
      observed in technical failure, pain scores, return to normal functioning, VCSS
      and recurrence rates post-intervention. Intragroup analysis: QoL measures (AVVQ,
      SF-36((r)), EQ-5D) and VCSS scores demonstrated significant improvement at 12 and
      52 weeks compared with baseline (P < 0.05). CONCLUSIONS: Increase in length of
      vein treated and energy delivery seems to improve short-term outcomes; however,
      operators need to be wary of a possible concurrent increase in paraesthetic
      complications.

PMID- 22357458
TI  - Neck duplex Doppler ultrasound evaluation for assessing chronic cerebrospinal
      venous insufficiency in multiple sclerosis patients.
AB  - INTRODUCTION: Recent clinical studies have suggested a relationship between
      multiple sclerosis (MS) and the occurrence of pathological changes in the
      jugular, vertebral and azygous veins that result in abnormal blood outflow from
      the brain and the spinal cord. Together, these pathological changes have been
      designated chronic cerebrospinal venous insufficiency (CCSVI). The aim of the
      present study was to evaluate the usefulness of duplex Doppler ultrasound in the
      evaluation of central nervous system venous outflow disturbances in patients
      suffering from MS. METHODS: We examined 181 patients with MS, diagnosed on the
      basis of the McDonald criteria, and 50 healthy volunteer controls. All patients
      underwent Doppler ultrasound examination of the internal jugular veins (IJV) and
      vertebral veins (VVs). The presence of outflow disturbances and morphological
      abnormalities were evaluated. RESULTS: Pathological changes in the extracranial
      jugular veins were diagnosed in 148/181 MS patients (82%) and 7/50 control group
      volunteers (14%). The following abnormalities in the MS group were revealed: the
      presence of a reflux in the IJVs and/or VVs (54%), narrowing (54%), a complete
      block in the flow through the IJV (10%) and an abnormal postural control of the
      cerebral outflow route (25%). These particular pathologies were of statistical
      significance in the MS group compared with the control group. This study also
      revealed a correlation between the occurrence of inverted flow in patients in a
      sitting position and chronic progressive MS (P = 0.0033). CONCLUSIONS: The
      examinations undertaken indicate a possible connection between MS and CCSVI. The
      widely accessible and highly sensitive and specific Doppler ultrasound test may
      be useful for revealing, and preliminary analysis of, CCSVI pathologies.

PMID- 22357459
TI  - Ultrasound-guided foam sclerotherapy within a rolling treatment programme is an
      effective low-cost treatment for superficial venous insufficiency.
AB  - AIMS: To review the results and cost of a rolling ultrasound-guided foam
      sclerotherapy (UGFS) treatment programme for patients with chronic superficial
      venous insufficiency. METHOD: A prospective study of a rolling treatment
      programme where patients were offered unlimited follow-up at intervals of 6-8
      weeks and further (top up) UGFS when necessary, until occlusion criteria were
      met. RESULTS: A total of 213 lower limbs with complete follow-up were included in
      the study. Median (range) age was 57 (16-94) years, maximum diameter of varicose
      vein was 10 (3-18) mm, C of CEAP (clinical, aetiological, anatomical and
      pathological elements) was 4 (2-6), number of treatment sessions was one (1-4)
      and follow-up was three (1.5-33) months. Satisfactory occlusion could not be
      achieved in nine (4%) limbs. The ratio of odds (95% CI) for requiring more than
      one treatment session was 3.58 (1.46-8.77), P = 0.002 for great saphenous
      varicosity and 2.11 (1.13-3.94), P = 0.015 for age 50 or more. There were 20
      (9.3%) immediate and 63 (29.5%) delayed adverse effects. All were minor except
      for one cutaneous nerve injury, one pulmonary embolism and one infected
      haematoma. The ratio for odds (95% CI) for post-treatment skin discolouration was
      2.59 (1.14-5.87), P = 0.017 for women and 1.32 (1.02-1.71), P = 0.032 for
      increasing sclerosant volume used. Service line costing per completed treatment
      episode was L115.22 (?130.07, $188.60). CONCLUSION: UGFS in a rolling treatment
      programme is safe and can achieve high occlusion rates at a low cost. Patients
      above the age of 50 with great saphenous varicosity are likely to require more
      than one treatment session.

PMID- 22357460
TI  - Risk of breastfeeding cessation among low-income women, infants, and children: a
      discrete time survival analysis.
AB  - BACKGROUND: Women who receive services from the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC) often stop breastfeeding earlier
      than recommended. Little is known about maternal background and intrapersonal
      variables that predict the timing of breastfeeding cessation over the 12-month
      postpartum period. OBJECTIVES: The aim of this study was to identify the maternal
      background and intrapersonal predictors associated with the timing of
      breastfeeding cessation in WIC participants over the course of the 12-month
      postpartum period. METHOD: Existing longitudinal survey and administrative data
      from low-income breastfeeding WIC recipients (n = 309) were analyzed using
      discrete time survival analysis. Risk of breastfeeding cessation was the outcome,
      and self-reported items were used to derive predictor variables that corresponded
      to the background and intrapersonal variables of the Interaction Model of Client
      Health Behavior. RESULTS: Rates of breastfeeding were low (31% at 6 months and 6%
      at 12 months). In the best fitting discrete time survival analysis model, women
      who were older and of Mexican ethnicity, who had previous breastfeeding
      experience, and who had breastfeeding support from family or friends were at
      lowest risk for breastfeeding cessation at each monthly interval. DISCUSSION:
      Breastfeeding duration rates were lower than Healthy People 2020 benchmarks of
      61% at 6 months and 34% at 12 months. Clinicians and researchers can use the
      findings from this study to develop interventions that are targeted to periods of
      greatest risk of premature breastfeeding cessation to prolong breastfeeding
      duration in this vulnerable population.

PMID- 22357461
TI  - [Management of children after renal transplantation: highlights for general
      pediatricians].
AB  - The number of children undergoing successful renal transplantations has been
      increasing steadily and as a result, general pediatricians are now more likely to
      encounter children with a kidney allograft in their practice. Although the
      medical care immediately after transplantation is mostly provided by transplant
      teams, more and more outpatient care will eventually be performed at the
      patient's local community. Medical care from general pediatricians is
      particularly important, especially for children who are residing far from
      transplant centers. As these children require prolong immunosuppressive therapies
      and are susceptible to various specific clinical problems, it is imperative for
      their primary care providers and pediatricians to be knowledgeable about their
      specific needs and be competent in providing care. This article highlights the
      roles and common practice related issues that pertain to general pediatricians in
      the care of pediatric renal allograft recipients.

PMID- 22357462
TI  - [Co-morbidity of attention deficit hyperactivity disorder in children with
      epilepsy].
AB  - OBJECTIVE: To estimate the prevalence of attention deficit hyperactivity disorder
      (ADHD) in children with epilepsy, and the factors that may contribute to the
      prevalence of co-morbidity between ADHD and epilepsy. METHODS: A total of 256
      children aged 6-15 years old who were diagnosed with epilepsy were enrolled. The
      prevalence of ADHD in children with epilepsy, and the factors that may contribute
      to the development of co-morbidity between ADHD and epilepsy were explored.
      RESULTS: The systematic evaluation in 192 patients was completed. Of the 192
      children, 81 (42.2%) were diagnosed with ADHD. The earlier the epilepsy onset,
      the higher the frequency of the co-morbidity of ADHD occurring. The longer the
      period of antiepileptic medication, the higher the prevalence of the co-morbidity
      of ADHD. Epileptic children receiving a combination of antiepileptic drugs had a
      higher prevalence of ADHD. ADHD was more common in children with some specific
      types of epilepsy, such as Lannox-Gastaut syndrome and generalized tonic-clonic
      epilepsy, or epilepsy with multifocal epileptic discharges in the EEG record.
      CONCLUSIONS: ADHD occurs frequently in children with epilepsy. The factors
      associated with increased risk of ADHD include the onset age of epilepsy, the
      types of seizures or epileptic syndromes, the epileptiform EEG discharges, and
      the effects of antiepileptic drugs.

PMID- 22357463
TI  - [Risk factors and pathogen distribution in premature infants with nosocomial
      sepsis].
AB  - OBJECTIVE: To investigate the main risk factors and pathogen distribution of
      nosocomial sepsis among premature infants. METHODS: The clinical data of 3418
      hospitalized premature infants from January 2003 to December 2010 were
      retrospectively analyzed for the risk factors and pathogen distribution of
      nosocomial sepsis. RESULTS: The incidence of neonatal nosocomial sepsis was 3.10%
      (106/3418), and the median age at diagnosis of neonatal nosocomial sepsis was 19
      (4-48) days. The major pathogens of the infections among these premature infants
      included gram-positive bacteria (45.2%), especially coagulase-negative
      Staphylococcus (24.3%), and gram-negative bacteria (41.7%), especially Klebsiella
      pneumoniae (25.2%), as well as fungus (13.0%). Logistic regression analysis
      showed that the main risk factors included low birth weight, retention of central
      venous catheters, and long duration of parenteral nutrition (OR: 3.765, 3.051,
      and 2.998, respectively; P<0.05). CONCLUSIONS: Low birth weight, retention of
      central venous catheters, and long duration of parenteral nutrition are the main
      risk factors for neonatal nosocomial sepsis, whereas the leading pathogen is
      Klebsiella pneumoniae.

PMID- 22357464
TI  - [Value of radiographic assessment scale in necrotizing enterocolitis].
AB  - OBJECTIVE: This study was conducted to determine the value of the radiographic
      assessment scale in the diagnosis of neonatal necrotizing enterocolitis, and as
      measured by need for surgery. METHODS: A total of 61 neonates were classified
      into three groups according to the Bell's Staging Criteria: NECI(n=25),
      NECII(n=11) and NEC III(n=25). Data on gestational age at birth, gender, birth
      weight, clinical manifestations, treatment and prognosis of the patients were
      collected. Radiographic assessment scale scores were evaluated by a pediatric
      radiologist. RESULTS: Radiographic assessment scale scores in the NECI, NECIIand
      NEC III groups were 3.2+/-1.4, 5.3+/-1.7 and 8.9+/-1.7, respectively (P<0.05).
      The score was highest in the NEC III group and lowest in the NECIgroup. Based on
      the different therapies, the NEC III group was subdivided into operative and non
      operative groups. Radiographic assessment scale scores in the two subgroups were
      8.71+/-1.86 and 9.36+/-1.21 respectively (P>0.05). Radiographic assessment scale
      scores in neonates with intestinal perforation (9.6+/-1.1) were higher than in
      those with intestinal necrosis (6.8+/-1.8) (P<0.05). The majority of patients
      (80%) who underwent operation had radiographic assessment scale scores above 7.
      The effective rate was 96% and 64% respectively in the NECIand the NECII groups.
      Of the children in the NECIII group, the cure rate was 71% in the operative
      group, and the effective rate was 9% in the non-operative group. CONCLUSIONS: The
      radiographic assessment scale may be used to evaluate the severity of disease in
      neonates with NEC. Patients with a score on the radiographic assessment scale
      above 7 have indications for surgical intervention and have better short-term
      treatment response rates.

PMID- 22357465
TI  - [Application of regionalized critical neonatal emergency transport system].
AB  - OBJECTIVE: To study the application of the regional critical neonatal emergency
      transport system (NETS) to provide evidence for the optimization of NETS in
      Beijing. METHODS: All the transported neonates in four hospitals in Haidian
      District, Beijing, between January 2009 and September 2010 were enrolled. The
      relevant clinical information of two referral hospitals was analyzed. RESULTS:
      The top three conditions requiring transport were pre-term delivery, diseases
      requiring surgical treatment, and respiratory diseases, which accounted for
      33.1%, 18.3%, and 14.8%, respectively. Active transport was performed in 95 cases
      (66.9%) and passive transport in 47 cases (33.1%). The age distribution of the
      neonates requiring transport was as follows: <6 hrs after birth (24.1%); 6-12 hrs
      (9.3%); 12-24 hrs (25.9%); and >24 hrs (40.8%). The mean time for transport from
      the hospital to a referral ward by ambulance was 28.0+/-11.1 minutes. Diseases
      requiring emergency surgical treatment were the leading cause of death,
      accounting for 53.8% of total deaths. The mortality rate was not significantly
      different between the neonates aged <6 hrs and >=6 hrs groups. CONCLUSIONS:
      Active transport remains the main transport pattern among these four hospitals.
      Neonates requiring surgical treatment have a high mortality rate, and thus
      special attention should be paid to their transport.

PMID- 22357467
TI  - [Evaluation of heart and liver iron deposition status in patients with beta-
      thalassemia intermedia and major with MRI T2* technique].
AB  - OBJECTIVE: To study the status of iron deposition in patients with beta
      thalassemia intermedia and major in mainland China. METHODS: The status of
      transfusion and chelation was examined in 39 patients with beta-thalassemia
      intermedia or major. Serum ferritin levels were measured. MRI T2* technique was
      used to detect cardiac and hepatic iron deposition. RESULTS: Serum ferritin
      levels ranged from the minimum of 1500 ng/mL up to a maximum of 11491 ng/mL. From
      liver MRI T2* measurement, 15 cases had severe hepatic iron deposition (38%) and
      moderate deposition was found in 15 cases (38%), mild in 7 cases (18%), and
      normal in 2 cases (5%). Heart MRI T2* showed severe heart iron deposition in 7
      cases (18%), mild in 5 cases (13%), and normal in 27 cases (69%). One case had
      cardiac arrhythmia. Four cases were over 20 years of age, and presented with
      gonadal function hypoplasia. The majority of patients did not receive regular
      transfusion and they had delayed, suboptimal chelation due to financial problems.
      Serum ferritin level was closely related with timing and dosage of chelation.
      CONCLUSIONS: In patients with beta-thalassemia who do not receive early regular
      transfusion and iron chelation therapy, iron deposition may occur at an early
      age. Important organs and tissue functional lesions and related complications
      also result. Relevant agencies and family members should be aware of this trend
      and develop appropriate strategies to improve the medical condition and quality
      of life of patients with this disorder.

PMID- 22357468
TI  - [Relationship between blood lactate level and disease severity in critically ill
      children].
AB  - OBJECTIVE: To study the relationship between blood lactate level and disease
      severity in critically ill children. METHODS: The clinical data of 232 children
      who were critically ill between September and December, 2010 were retrospectively
      studied. According to blood lactate levels within 24 hrs of admission, the 232
      patients were classified into three groups: normal (n=146), high lacticemia
      (n=72) and lactic acidosis (n=14). The circulation functions, pediatric critical
      illness scores and prognosis were compared among the three groups. RESULTS: The
      degree of sepsis among the three groups was different (chi2 = 13.592, P<0.01).
      The occurrence of septic shock in the lactic acidosis group (42.9%) was
      significant compared with that in the normal (7.5%) and the high lacticemia
      groups (11.1%). The pediatric critical illness scores were different among the
      three groups (chi2 = 12.854, P<0.05). The blood lactate level was significantly
      negatively correlated with the pediatric critical illness scores (r=-0.405,
      P=0.002). The prognosis among the three groups was also varied (chi2 = 25.599,
      P<0.01). The curative rate (7.1% vs 23.3%; P<0.05) and the improvement rate
      (28.6% vs 58.2%; P<0.05) in the lactic acidosis group were significantly lower
      than in the normal group, and the mortality (28.6%) was significantly higher than
      in the normal (5.5%) and the high lacticemia groups (6.9%). CONCLUSIONS: A higher
      blood lactic acid level is associated with a more severe illness state and a
      worse prognosis.

PMID- 22357466
TI  - [Gene expression of Notch1 and Jagged1 in children with acute leukemia].
AB  - OBJECTIVE: To study the gene expression of Notch1 and Jagged1 in children with
      acute leukemia (AL) and their possible roles in the pathogenesis of AL. METHODS:
      Mononuclear cells from bone marrow or peripheral blood of 47 children with AL and
      20 controls (normal children or children with nonmalignant hematologic disease)
      were collected from February 2009 to July 2011. A two-step method to semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to
      detect the gene expression of Notch1 and Jagged1. Of the 47 children with AL,
      there were 26 cases of B-ALL, 6 cases of T-ALL and 15 cases of AML. RESULTS: The
      positive expression rate of Notch1 in the ALL and AML groups was higher than in
      the control group (P<0.05). The expression level of Notch1 in T-ALL children was
      higher than in B-ALL children (P<0.01). The positive expression rate of Jagged1
      in the ALL and AML groups was not significantly different from the control group,
      however, the expression level of Jagged1 in the ALL and AML groups was higher
      than in the control group (P<0.05). CONCLUSIONS: There are significant
      differences in the gene expression of Notch1 between children with different
      types of ALL, and a higher expression of Notch1 relates to T-ALL. The activation
      of Notch1 signal is common in children with AL. The abnormal gene expression of
      Notch1 in children with AML shows the role of Notch1 in AML. The gene expression
      of Jagged1 in children with ALL or AML is abnormal, and this needs to be
      confirmed by further research.

PMID- 22357469
TI  - [Correlation between insulin resistance and myocardial injury  in critically ill
      children].
AB  - OBJECTIVE: To study the relationship between insulin resistance and myocardial
      injury in children with critical diseases in light of the fact that such children
      usually suffer from noticeable insulin resistance and myocardial injury. METHODS:
      Sixty-three children with critical diseases who were admitted between March 2010
      and June 2011 were enrolled to comprise a case group. Fasting blood glucose,
      serum insulin, myocardial enzyme, and troponin I (CTnI) levels were measured. The
      insulin resistance index (HOMA-IR) was calculated. The children were classified
      into two groups: insulin resistance (HOMA-IR>1.0; n=30) and non-insulin
      resistance (HOMA-IR<=1.0; n=33). Thirty healthy children served as the control
      group. RESULTS: HOMA-IR, lactate dehydrogenase (LDH), aspartate
      aminotransferaseaspartate transaminase (AST), creatine kinase (CK), isoenzymes of
      creating kinase (CK-MB), alpha-hydroxybuty rate dehydrogenase (alpha-HBDH) and
      CTnI in the insulin resistance group were higher than those in the non-insulin
      resistance and the control groups (all P<0.05). The non-insulin resistance group
      also showed obviously higher levels in terms of LDH, AST, CK, CK-MB, alpha-HBDH,
      and CTnI than the control group (P<0.05). In the insulin resistance group, there
      exists a positive correlation between HOMA-IR and such indicators as LDH, CK, CK
      MB, AST, alpha-HBDH and CTnI (r=0.697, 0.739, 0.781, 0.642, 0.381, 0.792
      respectively; all P<0.05). CONCLUSIONS: Insulin resistance makes myocardial
      injury more serious; HOMA-IR can serve as a forecast indicator for the degree of
      myocardial injury.

PMID- 22357470
TI  - [Relationship between TIM-4 polymorphism and childhood asthma].
AB  - OBJECTIVE: To elucidate whether the polymorphism of asthma immune regulator gene
      TIM-4 is associated with the risk of childhood allergic asthma in the southwest
      region of China. METHODS: TIM-4 gene promoter region RS6882076 and intron
      RS4704727 were studied. PCR-RFLP was used to test the genotypes of two
      polymorphism loci among 579 cases (average 7.2 years old) of asthma and 524
      controls (average 7.6 years old) in a case-control study. RESULTS: There were
      significant differences in the frequency of gene types at RS4704727 site between
      the asthma and the control groups (P<0.01). The results of PCR-RFLP showed that
      the polyporphisms of RS6882076 and RS4704727 in TIM-4 gene were present in this
      study population. The frequency of T allele at the RS4704727 site in the asthma
      group was significantly lower than that in the control group (OR=1.603; 95%CI
      1.304-1.971; P<0.01). There were no significant differences in the frequencies of
      gene types and allele at RS6882076 site between the two groups (P>0.05).
      CONCLUSIONS: RS4704727 polymorphism of TIM-4 gene may be associated with
      childhood asthma, providing a better understanding of the pathogenesis of
      childhood asthma in the Southwest region of China.

PMID- 22357471
TI  - [Epileptiform discharges and sleep structure in children with nocturnal
      epilepsy].
AB  - OBJECTIVE: To study the epileptiform discharges and sleep structure in children
      with nocturnal epilepsy. METHODS: A total of 54 children with nocturnal epilepsy
      (NE group) between December 2009 and June 2011 were enrolled in this study using
      a cluster sampling method. Their epileptiform discharges and sleep structure were
      monitored using nocturnal 12 h-video-echoencephalography (EEG) and
      polysomnography. Meanwhile, 40 age- and gender-matched normal children were
      enrolled as the control group. RESULTS: All the 54 children in the NE group
      suffered from epileptiform discharges and a varied number of clinical seizures,
      especially at S1 and S2 states. Compared with the control group, S1 and S2 states
      had significantly higher proportions in the NE group, and S3 and  S4 states and
      REM state had significantly lower proportions (P<0.01). CONCLUSIONS: Epileptiform
      discharges and clinical seizures are more common in children with nocturnal
      epilepsy, especially during the non-rapid eye movement sleep. Meanwhile,
      remarkably disordered sleep structure also exists.

PMID- 22357472
TI  - [An epidemiological survey of febrile convulsions among pupils in the Wenzhou
      region].
AB  - OBJECTIVE: To study the prevalence and clinical features of febrile convulsion
      (FC) among pupils in the Wenzhou region, Zhejiang Province, China. METHODS: Using
      a random stratified cluster sampling method, 6406 children under 12 years from
      two primary schools of urban areas and two primary schools of rural areas were
      surveyed. RESULTS: The prevalence of FC was 3.67% (235/6406). Most children
      (75.7%) experienced their first onset of FC at 6 months to 3 years of age
      (median: 16 months). The seizures were generalized (95.3%, 224/235), with a
      duration of less than 10 minutes (86.4%, 203/235). FC was developed into epilepsy
      in 13 children (5.5%) who all suffered from complex FC. Relapses were noted in 88
      cases (37.4%), among whom 38 patients had only 1 recurrence and 50 patients had 2
      or more relapses. EEG was performed in 200 cases, among whom 12(6.0%) showed
      abnormalities. CONCLUSIONS: The prevalence of FC is 3.67% among pupils in the
      Wenzhou region. The seizures are generalized, with a short duration. A part of
      complex FC can be developed into subsequent epilepsy.

PMID- 22357473
TI  - [Clinical features of drug-induced liver injury in children].
AB  - OBJECTIVE: To study the clinical features of drug-induced liver injury in
      children. METHODS: The clinical data of the hospitalized children with drug
      induced liver injury over 5 years were retrospectively reviewed. RESULTS: Of 641
      cases of hospitalized children with liver injury, there were 64 cases (10%) of
      drug induced liver injury. Hepatocellular injury was the most common type of drug
      induced liver injury (81%). The major drugs causing drug-induced liver injury
      included chemotherapy drugs, antibiotics and anti-tuberculosis drugs. Rash (16%),
      gastrointestinal reaction (15%), fever (14%) and liver intumescence (12%) were
      common clinical symptoms. A part of patients with drug-induced liver injury (11%)
      had no symptoms and signs. CONCLUSIONS: Drug-induced liver injury is one of the
      common causes of liver damage in hospitalized children. Some children with drug
      induced liver injury have no symptoms and signs. Hepatocellular injury is a major
      type of drug-induced liver injury in children, resulting less severe liver
      damage.

PMID- 22357474
TI  - [Recruitment maneuver in the treatment of young piglets with acute lung injury].
AB  - OBJECTIVE: To study the feasibility, efficiency and any benefits of recruitment
      maneuver (RM) in the facilitation of lung repair during recovery from ALI in
      acute lung injury (ALI) model of young piglets. METHODS: The piglet model of ALI
      was established by an intravenous injection of lipopolysaccharide (LPS). Twelve
      ALI piglets were randomly divided into two groups: conventional ventilation (CON)
      and RM with low tidal volume. Arterial blood gas, dynamic lung compliance (Cdyn)
      and systematic hemodynamics were monitored during the treatment. TGF-beta1 levels
      in bronchoalveolar lavage fluid (BALF) and plasma were measured. The mRNA
      expression of TGF-beta1 in the lungs was assessed by real time PCR. Lung tissue
      was examined for morphological changes. RESULTS: No significant difference was
      observed in cardiac output and peripheral vascular resistance (PVR) between the
      two groups. The extravascular lung water index (ELWI) from 6 hrs after ALI
      inducement and the pulmonary vascular permeability index (PVPI) 8 hrs after ALI
      inducement in the RM group decreased significantly compared with the CON group.
      Cdyn in the RM group increased quickly 1 hr after ALI inducement, and there was a
      significant difference between the two groups (P<0.05). P/F (ratio of PaO2 to
      FiO2) in the RM group was significantly higher than in the CON group from 2 hrs
      after ALI inducement (P<0.05). Alveolar-to-arterial oxygen difference in the RM
      group was obviously lower compared with the CON group from 2 hrs after ALI
      inducement (P<0.05). The levels of TGF-beta1 in plasma and BALF and the mRNA
      expression of TGF-beta1 in the lung tissue were lower than in the CON group.
      Volume density of alveolar aeration in the RM group was significantly higher than
      in the CON group, and the injury score in the RM group was lower (P<0.05).
      CONCLUSIONS: RM can improve gas exchange and Cdyn in the treatment of piglets
      with ALI. RM is a safe and effective approach to alveolar recruitment and can
      alleviate ventilation induced lung injury.

PMID- 22357475
TI  - [Effects of environmental enrichment on the repair and proliferation of neurons
      in neonatal rats with hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To study the effects of environmental enrichment on neuron
      proliferation, learning and memory ability and motor ability in neonatal rats
      with hypoxic-ischemic brain damage (HIBD). METHODS: One hundred and eight 7-day
      old Sprague-Dawley rats were randomly divided into three groups: sham operation
      (CON group), HIBD and intervention group. HIBD model was prepared according to
      the classic Rice-Vannucci method. Environmental enrichment was administered for
      the rats in the intervention group after HIBD inducement. Behavioral tests (Water
      maze test, Suspension test and Slope test) were performed and the number of
      neural cells in the left hippocampus was examined 7, 14 and 28 days after
      intervention. RESULTS: The pyramid cells in the hippocampus CA1 area in the HIBD
      group were significantly less than in the CON group at 7, 14 and 28 days
      (P<0.05). The number of pyramid cells in the hippocampus CA1 area in the
      intervention group was significantly higher than in the HIBD group (P<0.01) at 7,
      14 and 28 days. The hidden platform escape latency period (EL) in the Water maze
      test was significantly more prolonged and the cross-platform number within 2
      minutes was significantly less in the HIBD and the intervention groups than in
      the CON group at all observed time points (P<0.01). The EL was significantly
      shorter and the cross-platform number within 2 minutes was significantly higher
      in the intervention group than in the HIBD group at all observed time points
      (P<0.01). The maintain time and score in the Suspension test were significantly
      lower and the time in the Slope test was significantly more prolonged in the HIBD
      and intervention groups than in the CON group at 7, 14 and 28 days (P<0.01). An
      increased maintain time and score and a decreased time in the Slope test were
      found in the intervention group compared with the HIBD group at 14 and 28 days
      (P<0.01). CONCLUSIONS: Environmental enrichment can improve motor function,
      learning and memory ability, and promote the repair and proliferation of neurons
      in neonatal rats with HIBD.

PMID- 22357476
TI  - [Clinical analysis of permanent neonatal diabetes mellitus in 10 cases].

PMID- 22357477
TI  - [Application of continuous blood purification in critically ill children].

PMID- 22357478
TI  - [Misdiagnosis analysis of childhood ovary disease in 10 cases].

PMID- 22357479
TI  - [Neonatal pituitary stalk interruption syndrome: a case report].

PMID- 22357480
TI  - [Application of stem cell transplantation in kidney diseases].
AB  - This paper summarizes the current literature on the potential therapeutic role of
      stem cell transplantation for kidney injury and repair and focuses on the choice
      of types of stem cells, the method of transplantation, and the mechanisms of stem
      cell homing to injured renal tissues and its protective effects. The application
      of umbilical cord mesenchymal stem cells (UC-MSCs) shows wide prospects, but the
      approach and optimal dose of cell transplantation are under intensive
      investigation. Signals that regulate stem cell homing to injured renal tissues
      may be related to chemokines or factors released in the target site. Several
      studies have pointed out that paracrine and endocrine of stem cells are the most
      likely mechanism of action in the injured nephron. Many questions remain
      unanswered but stem cell-based therapy is a promising new strategy for acute and
      chronic kidney diseases.

PMID- 22357482
TI  - F-box protein AFB4 plays a crucial role in plant growth, development and innate
      immunity.

PMID- 22357481
TI  - Understanding cancer stem cell heterogeneity and plasticity.
AB  - Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo.
      It has been recently realized that even mouse and human embryonic stem cells
      under the best culture conditions are heterogeneous containing pluripotent as
      well as partially committed cells. Somatic stem cells in adult organs are also
      heterogeneous, containing many subpopulations of self-renewing cells with
      distinct regenerative capacity. The differentiated progeny of adult stem cells
      also retain significant developmental plasticity that can be induced by a wide
      variety of experimental approaches. Like normal stem cells, recent data suggest
      that cancer stem cells (CSCs) similarly display significant phenotypic and
      functional heterogeneity, and that the CSC progeny can manifest diverse
      plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of
      tumor development and progression, and by comparing with normal stem cell
      development. Appreciation of cancer cell plasticity entails a revision to the
      earlier concept that only the tumorigenic subset in the tumor needs to be
      targeted. By understanding the interrelationship between CSCs and their
      differentiated progeny, we can hope to develop better therapeutic regimens that
      can prevent the emergence of tumor cell variants that are able to found a new
      tumor and distant metastases.

PMID- 22357483
TI  - Trends in mortality from cancers of the breast, colon, prostate, esophagus, and
      stomach in East Asia:  role of nutrition transition.
AB  - Although substantial nutrition transition, characterized by an increased intake
      of energy, animal fat, and red meats, has occurred during the last several
      decades in East Asia, few studies have systematically evaluated temporal trends
      in cancer incidence or mortality among populations in this area. Therefore, we
      sought to investigate this question with tremendous public health implications.
      Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and
      stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea
      (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint
      regression was used to investigate trends in mortality of these cancers. A
      remarkable increase in mortality rates of breast, colon, and prostate cancers and
      a precipitous decrease in those of esophageal and stomach cancers have been
      observed in selected countries (except breast cancer in Hong Kong) during the
      study periods. For example, the annual percentage increase in breast cancer
      mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993
      in Korea, and mortality rates for prostate cancer significantly increased by 3.2%
      (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These
      changes in cancer mortality lagged ~ 10 years behind the inception of the
      nutrition transition toward a westernized diet in selected countries or regions.
      There have been striking changes in mortality rates of breast, colon, prostate,
      esophageal, and stomach cancers in East Asia during the last several decades,
      which may be at least in part attributable to the concurrent nutrition
      transition.

PMID- 22357484
TI  - [The protein expression profiles induced by trimethyltin chloride in Vero cells].
AB  - OBJECTIVE: To explore the biomarkers and mechanism of kidney toxicity induced by
      trimethyltin chloride (TMT-Cl) through analyzing the differences of protein
      expression profiles between vero cells and vero cells exposed to TMT-Cl. METHODS:
      The differences of protein expression levels of three paired samples of vero
      cells and vero cells exposed to TMT-Cl were compared by two-dimensional gel
      electrophoresis (2-DE) and liquid chromatography-electrospray ionization-linear
      trap quadrupole (LC-ESI-LTQ). The differences of expression levels of Annexin A1
      and alpha-Tubulin proteins were validated with western blot assay, and the
      differences of mRNA expression levels of Annexin A1 and alpha-Tubulin genes were
      detected with quantitative reverse transcriptase-polymerase chain reaction (qRT
      PCR). RESULTS: Fifteen spots of differential expression in protein profiles
      between vero cells and vero cells exposed to TMT-Cl were found, and 9 of these
      spots were identified by LC-ESI-LTQ. The expression levels of 3 proteins (Annexin
      A1,similar to RAN protein and a hypothetical protein) increased and the
      expression levels of 6 proteins(growth factor receptor-bound protein 10, tubulin
      alpha 6, heterogeneous nuclear ribonucleoprotein, similar to elongation factor
      SIII p15 subunit, S-adenosylhomocysteine hydrolase and a hypothetical protein)
      reduced. The expression levels of alpha-Tubulin protein and mRNA significantly
      decreased in vero cells exposed to TMT-Cl, as compared with vero cells (P <
      0.01). The expression of Annexin A1 protein in all exposure groups was
      significantly up-regulated, the expression of Annexin A1 mRNA in the groups
      exposed to 25 and 50 umol/L TMT-Cl was significantly down-regulated, and The
      expression of Annexin A1 mRNA in the group exposed to 100 umol/L TMT-Cl was
      significantly up-regulated (P < 0.01). CONCLUSIONS: The results of present study
      suggest that 9 proteins with differential expression detected by LC-ESI-LTQ may
      be related to the kidney toxicity induced by TMT-Cl, which can serve as the
      biomarkers of early diagnosis and therapeutic effect for the kidney toxicity
      induced by TMT-Cl.

PMID- 22357485
TI  - [Relevance between single nucleotide polymorphisms in nicotinic acetylcholine
      receptor genes and DNA damage levels in coke oven workers].
AB  - OBJECTIVE: To investigate the relevance between single nucleotide polymorphisms
      (SNPs) in CHRNA3-CHRNB4-CHRNA5 gene cluster and DNA damage levels in the coke
      oven workers. METHODS: A total of 309 male subjects from a steel plant in
      Northern China were divided into high exposure group (154 workers) and low
      exposure group (155 workers) according to the concentrations of plasma
      benzoapyrene-r-7, t-8, t-9, c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts. DNA
      damage levels of peripheral blood lymphocytes were examined by comet assay.
      Allelic discrimination of SNPs in CHRNA3-CHRNB4-CHRNA5 gene cluster were detected
      using Matrix-assisted laser desorption/ionization mass spectrometry. RESULTS: The
      Olive tail moment (OTM) (1.23 +/- 1.05) of peripheral blood lymphocytes in the
      high exposure group was significantly higher than that (0.80 +/- 1.07) in the low
      exposure group (P < 0.01). In the high exposure group, OTM (1.64 +/- 0.17) of
      subjects with rs667282CC genotype was significantly higher than those (0.95 +/-
      0.13 or 1.09 +/- 0.11) of subjects with rs667282CT genotype or rs667282TT + CT
      genotype (P < 0.01); OTM (1.60 +/- 0.17) of subjects with GG genotype at
      rs12910984 site was significantly higher than those (0.92 +/- 0.13 or 1.07 +/-
      0.10) of subjects with AG genotype or AG + AA genotype (P < 0.01); OTM (1.35 +/-
      0.17 or 1.64 +/- 0.17) of the TA/TA or CG/CG diplotype carriers was significantly
      higher than that (0.89 +/- 0.13) of TA/CG diplotype carriers (P < 0.05). However,
      the relevance between genotypes of these SNPs and the DNA damage levels was not
      found in the low exposure group. CONCLUSION: The rs667282CC genotype and
      rs12910984GG genotype on CHRNA3-CHRNB4-CHRNA5 gene cluster are associated with
      increased DNA damage levels in the high PAHs exposure group.

PMID- 22357486
TI  - [Effects of puerarin on proliferation, apoptosis and Kv1.5 gene expression of
      pulmonary artery smooth muscle cells induced by hypoxia].
AB  - OBJECTIVE: To study the effects of puerarin on proliferation, apoptosis and Kv1.5
      gene expression of rat pulmonary artery smooth muscle cells (PASMCs) induced by
      hypoxia. METHODS: The rat PASMCs were divided into 5 groups: control group,
      hypoxia group, hypoxia plus puerarin (1 * 10(-5) mol/L) group, hypoxia plus
      puerarin (1 * 10(-4) mol/L) group and hypoxia plus puerarin (1 * 10(-3) mol/L)
      group, and cultured at 37 degrees C for 24 h. The proliferation of rat PASMCs was
      detected by CCK-8 assay and flow cytometry, the activity of caspase-3 was
      measured with spectrophotometric method, Kv1.5 protein was detected by western
      blot, Kv1.5 mRNA was detected by real-time PCR. RESULTS: The cell viability and
      proportion of synthesis phase in control group were 0.940 +/- 0.045 and 9.67% +/-
      1.28%, which were significantly lower than those (1.296 +/- 0.034 and 18.19% +/-
      1.19%) in hypoxia group (P < 0.05). The Caspase-3 activity, Kv 1.5 protein and Kv
      1.5 mRNA in control group were 0.1073 +/- 0.0113, 0.886 +/- 0.038 and 0.0377 +/-
      0.0031, which were significantly higher than those (0.0664 +/- 0.0049, 0.602 +/-
      0.064 and 0.0108 +/- 0.0014) in hypoxia group (P < 0.05). As compared with
      hypoxia group, the cell viability and proportion of synthesis phase in 3 hypoxia
      plus puerarin groups significantly decreased, and the Caspase-3 activity, Kv 1.5
      protein and Kv 1.5 mRNA in 3 hypoxia plus puerarin groups significantly enhanced
      (P < 0.05). CONCLUSION: Puerarin could decrease the proliferation and increase
      the apoptosis induced by hypoxia in rat PASMCs, and the up-regulated expression
      of Kv1.5 gene may be the mechanism of puerarin effects.

PMID- 22357487
TI  - [Effects of hemoperfusion on plasma concentration and histopathological changes
      in paraquat poisoning rabbits].
AB  - OBJECTIVE: To observe the effects of hemoperfusion on plasma concentration and
      histopathological changes in paraquat (PQ) poisoning rabbits. METHODS: Sixteen
      rabbits were randomly divided into exposure group (PQ group, n = 8) and
      hemoperfusion plus PQ exposure group (HPQ group, n = 8). HPQ group were given
      hemoperfusion in 45 min after exposure to PQ. The plasma PQ concentrations at
      0.5, 1.0, 1.5, 2.0, 3.0, 6.0, 12.0, 24.0, 48.0 and 72.0 hours after exposure were
      measure in 2 groups. The histopathological changes of lung, liver and kidney were
      examined, the behavior changes and the survival number of 7 days were observed.
      RESULTS: The poisoning symptoms of HPQ group were generally better than those of
      PQ group, in each group six animals survived for 7d. The plasma PQ concentrations
      at 1.0, 1.5, 2.0, 3.0, 6.0, 12.0, 24.0, 48.0, 72.0 h after exposure in HPQ group
      were significantly lower than those in PQ group (P < 0.05 or P < 0.01). In HPQ
      group, the plasma PQ peak concentration [(5.01 +/- 0.15] ug/L], area under the
      curve [(54.03 +/- 5.31) mg*h(-1)*L(-1)] and PQ half-life time [(16.29 +/- 3.26)
      h] after treatment of HP were significantly lower than those [(11.97 +/- 0.75)
      ug/L, (141.40 +/- 10.10) mg*h(-1)*L(-1) and (31.16 +/- 9.85) h] in PQ group (P <
      0.05). The apparent volume of distribution and PQ clearance rate in HPQ group
      were significantly higher than those in PQ group (P < 0.05). Congestion, edema,
      cell infiltration and other pathological changes were found in lung, liver and
      kidney in PQ group under the light microscope, which were significantly more
      severe than those in HPQ group. The pathologic scores of lung tissue, liver and
      renal tubular damage on the 1st, 3rd, 7th days after exposure in HPQ group were
      significantly lower than those in PQ group (P < 0.05). CONCLUSION: When acute PQ
      poising, rabbits appeared the quick absorption, high toxicity and long half-life
      time of PQ. The early hemoperfusion can effectively remove the toxicant in plasma
      and reduce the pathological injury in major organs, which may be beneficial for
      further treatment.

PMID- 22357488
TI  - [The experimental study of suppressing silicosis fibrosis].
AB  - OBJECTIVE: To compare the difference of effects on SiO(2)-induced alveolitis and
      early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs)
      and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this
      effects. METHODS: The Primary BM-MSCs from Wistar male young rats were cultured
      and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were
      randomly divided into 3 groups:model group (10 rats),which was administered with
      SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group
      (20 rats),which was administered with SiO(2) by the trache, the next day,injected
      with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group
      (20 rats),which was administered with SiO(2) by the trache, the next day,injected
      with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On
      the 14th and 28th days after treatment, half of the animals were sacrificed,
      respectively, and the lungs were harvested for frozen section to observe the cell
      marked by DAPI. HE staining under a fluorescent microscope, and to observe the
      pulmonary alveolitis and fibrosis by HE and Masson staining under a light
      microscope. Western blot assay was used to detect the expression of HGF in rat
      lungs. The expression levels of tumor necrosis factor-alpha (TNF-alpha) in
      pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in
      pulmonary tissues were analyzed quantitatively by sample hydrolysis method.
      RESULTS: On the 14th and 28th days after treatment, the scores of pulmonary
      alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 +/-
      0.17, 2.8 +/- 0.14 and 0.1 +/- 0.11, 1.16 +/- 0.13, which were significantly
      lower than those (1.68 +/- 0.17, 1.58 +/- 0.31 and 0.54 +/- 0.15, 1.36 +/- 0.13)
      in BM-MSCs group, also which were significantly lower those (2.36 +/- 0.17, 2.80
      +/- 0.14 and 0.64 +/- 0.09, 1.84 +/- 0.17) in model group (P < 0.05); On the 14th
      and 28th days after treatment, the TNF-alpha contents of pulmonary tissues in
      pcDNA3.1-HGF plus BM-MSCs group were 280.4 +/- 23.11 and 249.78 +/- 22.33 pg/mg,
      which were significantly lower than those (341.58 +/- 35.34, 442.29 +/- 36.76
      pg/mg and 319.51 +/- 17.84, 348.53 +/- 33.95 pg/mg) in BM-MSCs and model groups
      (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of
      pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 +/- 0.04 and 0.65
      +/- 0.05 ug/mg, which were significantly lower than those (0.63 +/- 0.04, 1.04 +/
      0.07 ug/mg and 0.72 +/- 0.60, 1.39 +/- 0.60 ug/mg) in BM-MSCs and model groups
      (P < 0.05). CONCLUSION: The effects of BM-MSCs transfected by pcDNA3.1-HGF on
      suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better
      than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary
      inflammation.

PMID- 22357489
TI  - [Comparing the therapeutic effect of lung transplantation with the therapeutic
      effect of whole lung lavage for the patients with end-stage pneumoconiosis].
AB  - OBJECTIVE: To explore the therapeutic effects of lung transplantation (LTx) and
      whole lung lavage (WLL) for patients with end-stage pneumoconiosis. METHODS: From
      June 2002 to February 2011, 5 cases with end-stage pneumoconiosis were treated
      with LTx and 12 cases with end-stage pneumoconiosis were treated with WLL. The
      clinical symptoms, pulmonary functions, pulmonary artery pressures, blood gas
      analysis, imagings of chest and survival status were retrospectively analyzed.
      RESULTS: In LTx group, the clinical symptoms (cough, sense of suppression in the
      chest), pulmonary functions and blood gas indicators were improved, pulmonary
      artery pressures decreased to normal levels, the imaging of chest showed that the
      implanted lung inflated well and was with clear lung markings. But the
      contralateral lungs without treatment appeared the progression of disease in the
      imaging of chest. In WLL group, the clinical symptoms in a half year after
      treatment were improved but the symptomatic relief rate declined with time, the
      pulmonary functions in half year after treatment were improved but decreased
      after 2 years, the pulmonary artery hypertension enhanced generally, as compared
      with that prior to WLL. The disease progression in the chest imaging examination
      was not found in a half year after WLL, but appeared in 1 ~ 2 years after WLL.
      During following-up. the mean survival times in LTx and WLL groups were 40.5 and
      21.4 months, respectively. In LTx group, one patient died of multiple organ
      dysfunctions (MODS) caused by primary graft dysfunction (PGD), one case died of
      severe infection in seven months after LTx. Up to now, other 3 cases have
      survived for 65, 41 and 29 months, respectively. In WLL group, 3 cases died of
      pulmonary infection, 2 cases died of respiratory failure, one case died of heart
      failure and one case died of encephalon vascular accident, the mean survival time
      of these 7 patients was (19.0 +/- 8.7) months. So far other 5 cases have survived
      for 7, 9, 13, 18 and 26 months, respectively. CONCLUSION: LTx has greater risk of
      death during preoperative period, but patients after LTx may have long survival
      times with good quality of life. The clinical symptoms and pulmonary functions of
      patients can be improved temporarily after WLL, but the survival time of WLL is
      inferior to that of LTx.

PMID- 22357490
TI  - [Investigating the treatment of silicosis with autologous bone marrow-derived
      mesenchymal stem cells].
AB  - OBJECTIVE: To explore the safety and curative effects of autologous bone marrow
      derived mesenchymal stem cells (BMSCs) in the treatment of silicosis. METHODS:
      The protocol was approved by the Ethics Committee of the hospital, and ten
      patients with silicosis who had given written consent were enrolled in this
      study. BMSCs isolated from 100 ml of bone marrow for each case were purified and
      cultured. In each case the 3rd generation of qualified BMSCs (5 * 10(7)) were
      intravenously administered weekly for 3 weeks. Three cases among 10 patients were
      treated with BMSCs modified by hepatocyte growth factor (HGF) gene. The clinical
      symptoms, chest films, chest CT, pulmonary functions, T cells, serum IgG and
      ceruloplasmin (CP) were observed in 6 or 9 months after treatment. RESULTS: No
      obvious sub-effect was observed in cases treated with BMSCs, the clinical
      symptoms (such as cough, sputum and chest tightness) basically disappeared in 9
      months after treatment. Pulmonary function tests showed that FVC increased from
      71.2% +/- 17.0% to 84.0% +/- 10.9% (P < 0.01) and FEV1.0 increased from 67.5% +/-
      17.7% to 80.6% +/- 14.9% (P < 0.01). The levels of serum CP and IgG significantly
      decreased (P < 0.01). Further, the chest films and CT in cases treated with
      autologous BMSCs modified by HGF gene were improved to different extent.
      CONCLUSION: Treatment with autologous BMSCs modified by HGF gene exhibit a
      beneficial effect on silicosis.

PMID- 22357491
TI  - [Polymorphisms in Fas pathway genes and risk of coal worker pneumoconiosis].
AB  - OBJECTIVE: To explore the possible association between six single nucleotide
      polymorphisms (SNPs) of Fas pathway genes and the risks of coal worker
      pneumoconiosis (GWP). METHODS: This case-control study consisted of 511 male
      patients with CWP and 530 male controls from the same coal mines. Five SNPs of
      Fas pathway genes were detected by restriction fragment length polymorphisms (PCR
      RFLP) and CASP3 (rs6948) was genotyped by quantitative real-time polymerase chain
      reaction (qRT-PCR). RESULTS: There were no differences of genotype frequencies of
      6 SNPs between cases with CWP and controls. A significant increased risk of CWP
      was found in subjects with CASP8-652DD genotype as compared to subjects with
      CASP8-652II genotype (P < 0.05), and the further stratification analysis showed
      that smoking cases with CWP stage I, long exposure time and CASP8-652DD genotype
      had high risk of CWP (P < 0.05). The analysis of gene-gene interactions indicated
      that the carriers with FAS-1377GG/CASP8-652DD, FAS-670AG/CASP8-652DD and FASL
      844CT/CASP8-652DD had the increased risk of CWP, and the carriers with FAS
      1377GA/CASP8-652ID had the reduced risk of CWP. There were no significant
      differences of exposure times among the cases with CWP stage I and 3 genotypes of
      CASP8-652. CONCLUSION: CASP8-652 6N DD genotype may play a role in CWP
      development and interact with SNPs of FAS-1377, FAS-670 and FASL-844.

PMID- 22357492
TI  - [Pathologic observation on animal model of silicosis].
AB  - OBJECTIVE: To explore the pathological changes of pulmonary fibrosis induced by
      SiO2 in rats and pigs. METHODS: The silicosis models in rats and pigs were
      established by non-exposure method. The pathologic changes in lung tissues of
      rats and pigs were observed with HE staining under a light microscopy and under a
      transmission electron microscopy (TEM), the expression of cytokines was detected
      by immunohistochemistry. RESULTS: (1) The main pathologic changes of silicosis
      models in rats and pigs included: in 7 ~ 15 days after treatment, silica dusts,
      dust cells, a lot of macrophages, lung epithelial cells, a few neutrophils,
      macrophage alveolar inflammation and nodules of stage I were found in alveolar
      space; in 30 ~ 90 days after treatment, many nodules of stage I-III or IV with
      lymphocytes infiltration were observed in respiratory bronchioles, alveoli,
      interlobular septa, the subpleural and around blood vessels and bronchi. (2) The
      expression levels of CK protein, SP-A protein, CD68, b-FGF, TNF-alpha, IL-6, TGF
      beta1, NFKappa/P50, Kappa/P65 and VEGF reduced with exposure time, but still were
      higher than those of the control. (3) The shed alveolar type I cells,
      proliferation of alveolar type II cells or macrophages and activated cellular
      function induced by silica were observed under TEM. CONCLUSION: The development
      of pulmonary fibrosis in silicosis models corresponded with the process from
      macrophages alveolar inflammation to pulmonary fibrosis.

PMID- 22357493
TI  - MicroRNAs regulate B-cell receptor signaling-induced apoptosis.
AB  - Apoptosis induced by B-cell receptor (BCR) signaling is critical for antigen
      driven selection, a process critical to tolerance and immunity. Here, we examined
      the roles of microRNAs (miRNAs) in BCR signaling-induced apoptosis using the
      widely applied WEHI-231 model. Comparison of miRNA levels in BCR-stimulated and 
      unstimulated cells revealed that 39 miRNAs were differentially expressed upon
      stimulation of the BCR. Importantly, stimulation in the presence of anti-CD40
      antibodies, which rescues cells from BCR-induced apoptosis, prevented most
      changes in miRNA expression. Ectopic expression of mir-150 and mir-181a1b1,
      miRNAs that were upregulated upon BCR stimulation, resulted in inhibition of cell
      growth. Finally, we showed that ectopic expression of mir-150, mir-181a1b1 and
      mir-17~92 sensitized cells to anti-IgM stimulation-induced growth inhibition.
      Together, these results demonstrate that miRNAs are involved in BCR signaling,
      suggesting that they may have important roles in the regulation of B cell
      mediated tolerance and immunity.

PMID- 22357494
TI  - Development of a transcription-reverse transcription concerted reaction method
      for specific detection of human enterovirus 71 from clinical specimens.
AB  - A transcription-reverse transcription (RT) concerted reaction (TRCR) method was
      developed for rapid and specific detection of EV71 from clinical specimens. This
      method was validated with EV71 strains from all of the known genotypes (genotypes
      A, B1 to B5, and C1 to C5), with detection limits of 10 to 10(3) copies, and was
      useful for identification of EV71 from throat swabs of patients with hand, foot,
      and mouth disease (HFMD).

PMID- 22357495
TI  - Rapid and sensitive detection of Mycobacterium ulcerans by use of a loop-mediated
      isothermal amplification test.
AB  - This work reports the design and evaluation of a rapid loop-mediated isothermal
      amplification test for detecting Mycobacterium ulcerans DNA based on the
      multicopy insertion sequence IS2404. The test is robust and specific with a
      detection limit equivalent to 20 copies of the target sequence (0.01 to 0.1
      genome). The test has potential for the diagnosis of Buruli ulcer under field
      conditions.

PMID- 22357496
TI  - Sensitive and rapid detection of the new Delhi metallo-beta-lactamase gene by
      loop-mediated isothermal amplification.
AB  - New Delhi metallo-beta-lactamase 1 (NDM-1), which is associated with resistance
      to carbapenem, was first reported in 2008. A sensitive and rapid molecular assay
      to detect the plasmid bla(NDM-1) in clinical isolates is needed to control its
      spread. We describe a loop-mediated isothermal amplification (LAMP) assay for the
      rapid detection of bla(NDM-1) from pure culture and sputum, urine, and fecal
      samples. Eight sets of primers were designed to recognize six or eight distinct
      sequences on target bla(NDM-1), and one set was selected as the most appropriate
      set of primers for its rapid detection. The specificity and sensitivity of the
      primers in the LAMP reactions for bla(NDM-1) detection were determined. The
      sensitivity of the LAMP assay for bla(NDM-1) detection in sputum, urine, and
      fecal samples was also tested. Two methods, namely, monitoring of turbidity and
      addition of calcein to the reaction tube, were used to determine negative and
      positive results. The results showed that target DNA was amplified and visualized
      by the two detection methods within 70 min at an isothermal temperature of 65
      degrees C. The sensitivity of LAMP, with a detection limit of 10.70 pg/MUl DNA,
      was 100-fold greater than that of PCR. Thirteen infection bacterial strains
      without bla(NDM-1) were selected for testing of specificity, and the results of
      the amplification were negative, which showed that the primers had good levels of
      specificity. The LAMP method reported here is demonstrated to be a potentially
      valuable means for the detection of bla(NDM-1) and rapid clinical diagnosis,
      being fast, simple, and low in cost.

PMID- 22357497
TI  - Clinical validation of a point-of-care multiplexed in vitro immunoassay using
      monoclonal antibodies (the MSD influenza test) in four hospitals in Vietnam.
AB  - Point-of-care (POC) diagnostic tests for influenza can considerably shorten the
      time to clinical decision making. An investigational POC test based on a
      multiplexed immunoassay was developed by Meso Scale Diagnostics, LLC (MSD), with
      the objective to make a more sensitive rapid test that can also subtype influenza
      A viruses (1977 H1, H3, and H5). Between February and November 2010, we conducted
      a prospective multicenter study at four hospitals in Vietnam and compared the
      performance of this test to that of the WHO/CDC real-time reverse transcriptase
      PCR (RT-PCR) on nasal and throat swab specimens from patients presenting with
      influenza-like illness. Five hundred sixty-three adults and children with a
      median age of 25 months were enrolled. Sensitivity and specificity of the test
      with combined results from nasal and throat swab samples were 74.0% (131/177) and
      99.7% (351/352), respectively, compared to RT-PCR. The POC test was as sensitive
      for influenza virus B as for influenza virus A (74.4% [64/86] versus 73.6%
      [67/91]). The positivity rate was associated with lower cycle threshold values (a
      marker for higher viral loads), sample type (73.6% for nasal swab versus 52.4%
      for throat swab), and younger age. A total of 210 (18.7%) out of 1,126 MSD tests
      failed, and for 34 (6%) of patients, both test samples failed (these were
      excluded from the performance analysis). Subtyping could be assessed only for
      influenza virus A/H3N2, as 1977 H1N1 was not circulating at the time and no H5N1
      infected patients were enrolled, and was successful only in 9/54 patients
      infected with H3 influenza virus who had a positive POC test result for influenza
      virus A. This novel POC test provided highly sensitive detection of influenza
      viruses A and B compared to the reported sensitivities of other rapid tests.
      However, 18.7% of tests failed for technical reasons and subtyping for H3 was
      poor. Drawbacks to the technology include the requirement for a dedicated reader
      instrument and the need for continual updating of subtyping antibodies within the
      test array.

PMID- 22357498
TI  - Rapid direct testing of susceptibility of Mycobacterium tuberculosis to isoniazid
      and rifampin on nutrient and blood agar in resource-starved settings.
AB  - In this study, we evaluated the performance of blood agar (by macroscopic growth)
      and nutrient agar (by a microcolony detection method) for drug susceptibility
      testing of Mycobacterium tuberculosis against rifampin (RIF) and isoniazid (INH),
      using 67 smear-positive sputum specimens. The direct proportion method on
      Lowenstein-Jensen (LJ) medium was used as the "gold standard." Compared with LJ
      medium, results for both media were in 100% agreement for RIF, while for INH the
      agreement levels for blood agar and nutrient agar were 98% and 95%, respectively.
      Within 2 weeks, 100% of specimens yielded results on blood agar, while 96.8% of
      specimens yielded results on nutrient agar. Our study showed that blood agar and
      nutrient agar can be used as alternative media for direct susceptibility testing
      of RIF and INH, especially in resource-poor settings.

PMID- 22357499
TI  - Development and evaluation of a PCR assay for tracking the emergence and
      dissemination of Haitian variant ctxB in Vibrio cholerae O1 strains isolated from
      Kolkata, India.
AB  - A PCR-based assay was developed to discriminate the classical, El Tor, and
      Haitian types of ctxB alleles. Our retrospective study using this newly developed
      PCR showed that Haitian ctxB first appeared in Kolkata during April 2006, and
      93.3% of strains isolated during 2011 carried the new allele. Dendrogram analysis
      showed a pulsed-field gel electrophoresis (PFGE) pattern of the new variant
      strains isolated recently that was distinct from the PFGE pattern of the strains
      carrying classical ctxB that closely matched the 2006 to 2007 variant strains.

PMID- 22357500
TI  - Performance of commercial reverse line blot assays for human papillomavirus
      genotyping.
AB  - The performance of three line blot assays (LBAs), the Linear Array HPV genotyping
      assay (LA) (Roche Diagnostics), INNO-LiPA HPV Genotyping Extra (LiPA)
      (Innogenetics), and the reverse hybridization assay (RH) (Qiagen), was evaluated
      using quantitated whole genomic human papillomavirus (HPV) plasmids (types 6, 11,
      16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, and 68b) as well as epidemiologic
      samples. In a plasmid titration series, LiPA and RH did not detect 50
      international units (IU) of HPV type 18 (HPV18) in the presence of 5 * 10(4) IU
      or more of HPV16. HPV DNA (1 to 6 types) in the plasmid challenges at 50 IU or
      genome equivalents (GE) were identified with an accuracy of 99.9% by LA, 97.3% by
      LiPA, and 95.4% by RH, with positive reproducibility of 99.8% (kappa = 0.992),
      88.2% (kappa = 0.928), and 88.1% (kappa = 0.926), respectively. Two instances of
      mistyping occurred with LiPA. Of the 120 epidemiologic samples, 76 were positive
      for high-risk types by LA, 90 by LiPA, and 69 by RH, with a positive
      reproducibility of 87.3% (kappa = 0.925), 83.9% (kappa = 0.899), and 90.2% (kappa
      = 0.942), respectively. Although the assays had good concordance in the clinical
      samples, the greater accuracy and specificity in the plasmid panel suggest that
      LA has an advantage for internationally comparable genotyping studies.

PMID- 22357501
TI  - Detection of carbapenemase producers in Enterobacteriaceae by use of a novel
      screening medium.
AB  - A Drigalski agar-based culture medium containing an ertapenem, cloxacillin, and
      zinc sulfate (Supercarba medium) was tested for screening carbapenemase-producing
      members of the family Enterobacteriaceae. OXA-48 (n = 44), NDM (n = 25), VIM or
      IMP (n = 27), and KPC producers (n = 18) were detected with a low detection
      limit. Its overall sensitivity (95.6%) was higher than those of the currently
      available ChromID ESBL (bioMerieux) and CHROMagar KPC (CHROMagar) screening
      media. The Supercarba medium provides a significant improvement for detection of
      the most common types of carbapenemase producers.

PMID- 22357502
TI  - Precaution for using nucleic acid-based methods to detect Aeromonas.

PMID- 22357503
TI  - Identification of a C2 subgenogroup strain of enterovirus 71 in a retrospective
      study in Shandong Province, China, from 1990 to 2010.

PMID- 22357504
TI  - Development of a loop-mediated isothermal amplification assay for rapid detection
      of capripoxviruses.
AB  - Sheep pox (SP), goat pox (GP), and lumpy skin disease (LSD), caused by
      capripoxviruses (CaPVs), are economically important diseases of sheep, goats, and
      cattle, respectively. Here, we report the development of a loop-mediated
      isothermal amplification (LAMP) assay for rapid detection of CaPVs. LAMP primers
      were designed to target a conserved gene encoding the poly(A) polymerase small
      subunit (VP39) of CaPVs. Hydroxynaphthol blue (HNB) was incorporated to monitor
      assay progress by color change from violet when negative to sky blue when
      positive, and results were verified by agarose gel electrophoresis. The LAMP
      assay was shown to be highly specific for CaPVs, with no apparent cross
      reactivity to other related viruses (near neighbors) or viruses that cause
      similar clinical signs (look-a-like viruses). The performance of LAMP was
      compared to that of a highly sensitive quantitative real-time PCR (qPCR) assay.
      LAMP and qPCR exhibited similar analytical sensitivities, with limits of
      detection of 3 and 8 viral genome copies, respectively. Diagnostic specificity
      was assessed on 36 negative specimens, including swabs and EDTA blood from
      control sheep, goats, and cattle. Diagnostic sensitivity was assessed on 275
      specimens, including EDTA blood, swabs, and tissues from experimentally infected
      sheep, goats, and cattle. Overall agreement on diagnostic test results between
      the two assays was 90 to 95% for specificity and 89 to 100% for sensitivity. The
      LAMP assay described in this report is simple to use, inexpensive, highly
      sensitive, and particularly well suited for the diagnosis of capripox in less
      well equipped laboratories and in rural settings where resources are limited.

PMID- 22357505
TI  - Biomedical mass spectrometry in today's and tomorrow's clinical microbiology
      laboratories.
AB  - Clinical microbiology is a conservative laboratory exercise where base
      technologies introduced in the 19th century remained essentially unaltered. High
      tech mass spectrometry (MS) has changed that. Within a few years following its
      adaptation to microbiological diagnostics, MS has been introduced, embraced, and
      broadly accepted by clinical microbiology laboratories throughout the world as an
      innovative tool for definitive bacterial species identification. Herein, we
      review the current state of the art with respect to this exciting new technology
      and discuss potential future applications.

PMID- 22357506
TI  - The first locally acquired human infection of Echinococcus multilocularis in The
      Netherlands.
AB  - In the northern part of Western Europe, Echinococcus multilocularis is primarily
      detected in and spreading among foxes. The present case marks E. multilocularis
      as an emerging pathogen for humans, as it describes the first human case of
      probably locally acquired E. multilocularis in The Netherlands, with various
      interesting clinical aspects.

PMID- 22357507
TI  - Epidemiology of Klebsiella oxytoca-associated diarrhea detected by Simmons
      citrate agar supplemented with inositol, tryptophan, and bile salts.
AB  - We studied the clinical and epidemiological characteristics of Klebsiella oxytoca
      associated diarrhea in hospitalized patients in Hong Kong. Between 1 November
      2009 and 30 April 2011, all inositol-fermenting colonies found on Simmons citrate
      agar supplemented with inositol, tryptophan, and bile salts (SCITB agar) used for
      the culturing of diarrheal stool samples were screened by a spot indole test for
      K. oxytoca. The overall sensitivity of SCITB agar plus the spot indole test
      (93.3%) for the detection of K. oxytoca in stool samples was superior to that of
      MacConkey agar (63.3%), while the specificities were 100% and 60.4%,
      respectively. The former achieved a 23-fold reduction in the workload and cost of
      subsequent standard biochemical identifications. Cytotoxin production and the
      clonality of K. oxytoca were determined by a cell culture cytotoxicity
      neutralization assay using HEp-2 cells and pulsed-field gel electrophoresis
      (PFGE), respectively. Of 5,581 stool samples from 3,537 patients, K. oxytoca was
      cultured from 117/5,581 (2.1%) stool samples from 104/3,537 (2.9%) patients.
      Seventy-six of 104 (73.1%) patients with K. oxytoca had no copathogens in their
      diarrheal stool samples. Twenty-four (31.6%) of 76 patients carried cytotoxin
      producing strains, which were significantly associated with antibiotic therapy
      after hospital admission (50% versus 21.2%; P = 0.01). Health care-associated
      diarrhea was found in 44 (42%) of 104 patients with K. oxytoca, but there was no
      epidemiological linkage suggestive of a nosocomial outbreak, and PFGE showed a
      diverse pattern. None of the patients with cytotoxin-producing K. oxytoca
      developed antibiotic-associated hemorrhagic colitis, suggesting that K. oxytoca
      can cause a mild disease manifesting as uncomplicated antibiotic-associated
      diarrhea with winter seasonality.

PMID- 22357508
TI  - Clinical and microbiologic characteristics of invasive Streptococcus pyogenes
      infections in north and south India.
AB  - The lack of epidemiologic data on invasive Streptococcus pyogenes infections in
      many developing countries is concerning, as S. pyogenes infections are commonly
      endemic in these areas. Here we present the results of the first prospective
      surveillance study of invasive Streptococcus pyogenes infections in India. Fifty
      four patients with invasive S. pyogenes infections were prospectively enrolled at
      two study sites, one in the north and one in the south of India. Sterile-site
      isolates were collected, and clinical information was documented using a
      standardized questionnaire. Available acute-phase sera were tested for their
      ability to inhibit superantigens produced by the patient's own isolate using a
      cell-based neutralizing assay. The most common clinical presentations were
      bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two
      cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis
      were identified. Characterization of the isolates revealed great heterogeneity,
      with 32 different emm subtypes and 29 different superantigen gene profiles being
      represented among the 49 sterile-site isolates. Analyses of acute-phase sera
      showed that only 20% of the cases in the north cohort had superantigen
      neutralizing activity in their sera, whereas 50% of the cases from the south site
      had neutralizing activity. The results demonstrate that there are important
      differences in both clinical presentation and strain characteristics between
      invasive S. pyogenes infections in India and invasive S. pyogenes infections in
      Western countries. The findings underscore the importance of epidemiologic
      studies on streptococcal infections in India and have direct implications for
      current vaccine developments.

PMID- 22357509
TI  - Elevation of urine trypsinogen 2 is an independent risk factor for pancreatic
      fistula after pancreaticoduodenectomy.
AB  - OBJECTIVES: Previous reports suggested that the urine trypsinogen 2 (U-TRP2) test
      might be a valuable method for the diagnosis of postoperative pancreatitis after
      pancreatic surgery. We hypothesize that the elevation of U-TRP2 level after
      pancreaticoduodenectomy (PD) could be associated with the occurrence of
      postoperative pancreatic fistula (POPF). METHODS: A total of 130 consecutive
      patients undergoing PD with duct-to-mucosa pancreaticogastrostomy were included.
      Urine samples for evaluation of U-TRP2 levels were collected prospectively. Risk
      factors for POPF were evaluated using univariate and multivariate analyses.
      RESULTS: Of 130 patients, 19 developed POPF; grade A in 14 (11%), grade B in 3
      (2%), and grade C in 1 (1%). Univariate analysis demonstrated that a
      nonobstructed main pancreatic duct, a pancreatic duct less than 3 mm, soft
      texture of the pancreatic gland, a PD with antrectomy, PD with hepatic resection,
      hyperamylasemia, and elevation of U-TRP2 levels (>50 MUg/L) were significantly
      associated with POPF (P < 0.05). By multivariate analysis, elevation of U-TRP2
      levels (odds ratio = 4.544, P = 0.029) was the only independent risk factor that
      correlated with POPF. CONCLUSIONS: Elevation of U-TRP2 level is an independent
      risk factor for POPF after PD. Elevated U-TRP2 level might be the consequence of
      the postoperative pancreatitis, and postoperative pancreatitis may play an
      important role in the pathogenic mechanism of POPF after PD.

PMID- 22357510
TI  - Isolation of more potent oncolytic paramyxovirus by bioselection.
AB  - Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented
      single-stranded RNA genome. In this report, a recombinant oncolytic NDV was
      passaged in human tumor xenografts and reisolated and characterized after two
      rounds of bioselection. Several isolates could be recovered that differed from
      the parental virus with respect to virus spread in tumor cells and the ability to
      form syncytia in human tumor cells. Three isolates were identified that
      demonstrated superior oncolytic potency compared with the parental virus as
      measured by increased oncolytic potency in confluent tumor cell monolayers, in
      tumor cell spheroids and in a mouse xenograft tumor model. The surface proteins F
      and HN were sequence analyzed and characterized for fusogenicity. The present
      study demonstrates that in vivo NDV bioselection can enable the isolation of
      novel, oncolytic NDV and thus represents a powerful methodology for the
      development of highly potent oncolytic viruses.

PMID- 22357513
TI  - [Effects of DNA polymerase beta on the genotoxicity and genetic instability
      induced by benzo(a)pyrene].
AB  - OBJECTIVE: To explore the effects of DNA polymerase beta expression level on the
      genotoxicity and genetic instability induced by benzo(a)pyrene (BaP),and provide
      experimental the basis for further study on the carcinogenic molecular mechanism
      of BaP. METHODS: Three kinds of cell lines with the identical genetic background,
      polbeta wild-type cells (polbeta+/+), polbeta null cells (polbeta-/-) and polbeta
      overexpression cells (polbeta oe) were applied as cellular models. The oxidative
      damage, genotoxicity and genetic instability induced by BaP were analyzed by
      using different methods respectively. RESULTS: Cell viability and colony forming
      ability of 3 kinds of cell lines exposed to BaP decreased with BaP. After treated
      with 5 and 20 umol/L concentration of BaP, fluorescence intensity of polbeta-/-
      cell line was significantly higher than that of other two cell lines (P < 0.05).
      When treated with 5.00 umol/L and 20.00 umol/L concentration of BaP, the SOD
      activities (76.56 +/- 2.84 and 62.78 +/- 4.28 U/mg pro) of polbeta-/- cell line
      were significantly lower than that (84.85 +/- 3.59) of control group and those
      (85.21 +/- 3.20 and 76.90 +/- 3.38 U/mg pro) of polbeta+/+ cell line. In 20.00
      umol/L BaP group. SOD activity (82.59 +/- 4.64 U/mg pro) of polbeta oe cell line
      was lower than that (88.58 +/- 6.77 U/mg pro) of control but higher than that of
      polbeta+/+ cell line (P < 0.05). In 1.25, 5.00 and 20.00 umol/L concentration BaP
      groups, the micronucleus rates of polbeta-/- cell line were much higher than
      those of polbeta+/+ cell line (P < 0.05). In 5.00 and 20.00 umol/L concentration
      BaP groups, the micronucleus rates of polbeta oe cell line were significantly
      lower than those of polbeta+/+ line (P < 0.05). In 5.00 and 20.00 umol/L
      concentration BaP groups, HPRT gene mutation frequencies (26.16 * 10(-6) and
      37.51 * 10(-6); 27.68 * 10(-6) and 38.63 * 10(-6)) in polbeta-/- cells and
      polbeta oe cells were significantly higher than those (19.76 * 10(-6) and 24.78 *
      10(-6)) of polbeta+/+ cells (P < 0.05). CONCLUSION: Polbeta could play a role in
      protecting the cells from the genotoxicity and genetic instability induced by
      BaP, and the normal expression level of polbeta was indispensable for maintaining
      genome stability.

PMID- 22357512
TI  - Overexpression of adiponectin promotes focal angiogenesis in the mouse brain
      following middle cerebral artery occlusion.
AB  - Recent studies indicate that overexpression of adiponectin (APN) could attenuate
      ischemic brain injury. However, the mechanism of APN effect remains unclear. In
      this study, we investigated the cellular mechanisms of APN action during cerebral
      ischemia. Adult mice (n=120) received an intracerebral injection of adeno
      associated viral vector carrying the APN gene (AAV-APN). The mice were subjected
      to a transient ispilateral middle cerebral artery occlusion (tMCAO) after 7-day
      AAV-APN gene transfer. Cortical atrophy volume, neurological function,
      microvessels counts, phospho-AMPK and downstream angiogenic factor vascular
      endothelial growth factor (VEGF) were examined. Overexpression of APN was
      observed in the mouse brain following AAV-APN gene transfer. Cortical atrophy
      volume was attenuated in the AAV-APN-transduced mice compared with the AAV-GFP
      and saline-treated mice (7.9 +/- 0.6%, 19.8 +/- 0.3% and 20.3 +/- 1.1%,
      respectively, P<0.05), with significant improvement in neurological function and
      an increased number of microvessels (199 +/- 5 vs 151 +/- 4 and 148 +/- 4 mm(-2),
      P<0.01). Furthermore, the expression of phospho-AMPK and VEGF were increased in
      the AAV-APN-transduced compared with the control mice (P<0.01), whereas
      inhibiting phospho-AMPK, reducing VEGF expression and attenuating the effect of
      APN on brain atrophy and angiogenesis (P<0.01). APN overexpression attenuates
      ischemia-induced brain atrophy and has improvement in neurological function. The
      consequence is related to promotion of focal angiogenesis. The AMPK signaling
      pathway has an important role in upregulating angiogenic factor VEGF.

PMID- 22357514
TI  - [The study of the differential gene expression profiles related to toxic effects
      in rats exposed to silica].
AB  - OBJECTIVE: To study the differential gene expression profiles related to toxic
      effects in rats exposed to silica. METHODS: Wistar rats exposed to SiO2 (50
      mg/ml) and 1 ml normal saline by intratracheal injection served as the exposure
      and control groups, on the 14th day after exposure all rats were executed and the
      rat lung tissues were obtained. The differential gene expression profiles in the
      lung tissues of rats exposed to silica were detected using confocal fiber beads
      gene chip technique, and the differential expression profiling data were analyzed
      using the database for annotation, visualization and integrated discovery (DAVID)
      bioinformation analysis tool. RESULTS: The results of present study indicated
      that 1567 genes with differential expression were identified in 22107 genes of
      rat lung tissues in exposure group, including 765 up-regulated genes and 802 down
      regulated genes as compared to control group. In the 461 genes related to toxic
      effects, 285 genes were up-regulated and 176 genes were down-regulated in
      exposure group. The trends of up-regulation of HMOX1 and SOD2 genes in RT-PCR
      assay were similar to those in gene chip technique. CONCLUSION: A large number of
      genes related to toxic effects in the rats with silica-induced pulmonary fibrosis
      appeared up-regulation or down-regulation. There may be a complex gene regulation
      network in the pulmonary fibrosis induced by SiO2, and the toxicological
      mechanism is an important part in the development of pulmonary fibrosis.

PMID- 22357515
TI  - [The roles of activated protein-1 and cell cycle protein in silica-induced cell
      cycle changes].
AB  - OBJECTIVE: To investigate the roles of cyclin D1 and CDK4 in the cell cycle
      changes of human embryonic lung fibroblasts (HELFs) exposed to silica. METHODS:
      HELFs were divided into 4 groups: control group, curcumin (20 umol/L for 1 h)
      group, silica (200 ug/ml for 24 h) group and curcumin plus silica group, i.e.
      after exposure to 20 umol/L curcumin for 1h, the HELFs were treated with 200
      ug/ml silica for 24 h. Western blot and Immunofluorescence assays were utilized
      to detect the expression levels of cyclin D1, CDK4 and E2F1/4. Flow cytometry was
      used to detect the cell cycle progression, the RNA transfection technique was
      used to investigate the silica-induced signal pathway and the roles of which in
      silica-induced cell cycle changes. RESULTS: The expression levels of cyclin D1
      and CDK4 significantly increased and the expression level of E2F-4 decreased
      obviously, but the expression level of E2F-1 did not significantly change in
      silica group. The proportion of G1 phase cells obviously decreased and the
      proportion of S phase cells significantly increased in silica group, as compared
      with control group (P < 0.05). When suppressing the expression of cyclin D1 or
      CDK4, the proportions of cells in G1 phase in anti-D1 plus silica group and anti
      K4 plus silica group did not obviously change, as compared with control group.
      When suppressing AP-1 activity, the cyclin D1 and CDK4 expression levels
      decreased and the E2F-4 expression level increased in curcumin plus silica group,
      as compared with silica group. CONCLUSION: The results of present suggested that
      200 ug/ml silica could induce the high expression of cyclin D1 and CDK4 and the
      low expression of E2F-4, resulting in the cell cycle changes by AP-1/cyclin D1
      pathway in HELFs.

PMID- 22357511
TI  - Intracellular transport of recombinant adeno-associated virus vectors.
AB  - Recombinant adeno-associated viral vectors (rAAVs) have been widely used for gene
      delivery in animal models, and are currently evaluated for human gene therapy
      after successful clinical trials in the treatment of inherited, degenerative or
      acquired diseases, such as Leber congenital amaurosis, Parkinson disease or heart
      failure. However, limitations in vector tropism, such as limited tissue
      specificity and insufficient transduction efficiencies of particular tissues and
      cell types, still preclude therapeutic applications in certain tissues. Wild-type
      adeno-associated viruses (AAVs) are defective viruses that require the presence
      of a helper virus to complete their life cycle. On the one hand, this unique
      property makes AAV vectors one of the safest available viral vectors for gene
      delivery. On the other, it also represents a potential obstacle because rAAV
      vectors have to overcome several biological barriers in the absence of a helper
      virus to transduce successfully a cell. Consequently, a better understanding of
      the cellular roadblocks that limit rAAV gene delivery is crucial and, during the
      last 15 years, numerous studies resulted in an expanding body of knowledge of the
      intracellular trafficking pathways of rAAV vectors. This review describes our
      current understanding of the mechanisms involved in rAAV attachment to target
      cells, endocytosis, intracellular trafficking, capsid processing, nuclear import
      and genome release with an emphasis on the most recent discoveries in the field
      and the emerging strategies used to improve the efficiency of AAV-derived
      vectors.

PMID- 22357516
TI  - [Study on mRNA expression of immune-related genes in patients with allergic
      dermatitis induced by trichloroethylene].
AB  - OBJECTIVE: To study mRNA expression of immune-related genes (Foxp3, GATA3, CTLA4
      and T-bet) in peripheral blood of the patients with allergic dermatitis induced
      by trichloroethylene (TCE). METHODS: The peripheral blood samples were collected
      from 8 healthy workers (control group) and 8 patients with allergic dermatitis
      induced by TCE (case group). Real-time quantitative PCR was applied to detect
      mRNA expression of immune-related genes (Foxp3, GATA3, CTLA4, T-bet). RESULTS:
      The mRNA expression levels of Foxp3, GATA3 and CTLA4 genes increased by 115%, 97%
      and 241% in case group, as compared with control group (P < 0.01). The mRNA
      expression level of T-bet gene decreased by 47% in case group, as compared with
      control group (P < 0.01). CONCLUSION: The mRNA expression levels of some immune
      related genes changed in patients with allergic dermatitis induced by TCE, those
      genes may play an important role in TCE-induced allergy.

PMID- 22357517
TI  - [Effects of benzo(a)pyrene on apoptosis of neuronal cells and expression of Bcl-2
      and Bax proteins in rat brain tissue].
AB  - OBJECTIVE: To observe the effects of Benzo(a)pyrene (BaP) on apoptosis of
      neuronal cells and expression of Bcl-2 and Bax proteins and to explore the
      mechanism of neurotoxicity induced by BaP in rats. METHODS: A total of 32 SD rats
      were divided randomly into 4 groups, i.e. 3 BaP (126.2, 63.1 and 31.5 ug/kg)
      groups and a solvent control (50 ug/kg olive oil) group. All rats were exposed to
      BaP or olive oil by lateral cerebral ventricle micro-injection 1 time a week for
      3 weeks. The apoptosis of neuronal cells was detected with TdT-mediated dUTP
      biotin nicked labeling (TUNEL) assay and the expression levels of Bcl-2 and Bax
      were measured with SABC immunohistochemistry in the cerebral cortex and
      hippocampus tissues of rats. RESULTS: The results of TUNEL assay showed that
      apoptosis bodies on the surface of the neurons in the cerebral cortex and
      hippocampus were clearly observed and the number of apoptosis bodies increased
      with BaP. Apoptosis indexes (AIs) of the rat cerebral cortex and hippocampus in
      high exposure group were significantly higher than those in control group (P <
      0.05 or P < 0.01). The analysis of immunohistochemistry showed that the Bcl-2
      expression levels significantly decreased, the Bax expression levels obviously
      increased and the ratio of Bcl-2 to Bax decreased in the rat cerebral cortex and
      hippocampus of medium and high exposure groups, as compared with control group (P
      < 0.05 or P < 0.01). In the rat cerebral cortex and hippocampus, there were the
      negative correlation (r = -0.927, P < 0.01; r = -0.934, P < 0.01) between AI and
      Bcl-2, the positive correlation (r = 0.858, P < 0.01; r = 0.847, P < 0.01)
      between AI and Bax and the negative correlation (r = -0.939, P < 0.01; r = 
      0.942, P < 0.01) between AI and Bcl-2/Bax. CONCLUSION: BaP could induce the
      apoptosis of neuronal cells in the rat cerebral cortex and hippocampus. Bcl-2 and
      Bax protein expression may play an important role in the apoptosis of neuronal
      cells induced by BaP.

PMID- 22357518
TI  - [The role of CYP2E1 in the protection of garlic oil's from n-hexane-induced
      neurotoxicity].
AB  - OBJECTIVE: To study the role of CYP2E1 in the protective effects and mechanism of
      garlic oil (GO) on the peripheral nerve injuries induced by n-hexane. METHODS:
      Fifty male Wistar rats were randomly divided into five groups (n = 10): the
      control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose
      GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane
      groups. All rats were treated by intragastric administration 6 times a week for
      10 weeks. The gait scores were determined every two weeks for monitoring the
      peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and
      expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined. RESULTS:
      As compared with control group, the content and activity of hepatic CYP2E1 in GO
      control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and
      activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2%
      respectively (P < 0.01). As compared with model group, the contents of hepatic
      CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1%
      respectively, the activities of hepatic CYP2E1 in low dose and high dose GO
      groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum
      2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7%
      respectively (P < 0.01). The gait scores in model, low dose and high dose GO
      groups were significantly lower than that in control group, but the gait scores
      in low dose and high dose GO groups were significantly lower than that in model
      group (P < 0.05). CONCLUSION: Garlic oil can effectively reduce the peripheral
      neurotrosis induced by n-hexane due to the decreased content and activity of
      hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

PMID- 22357519
TI  - Vascular ventricular coupling in patients with malignant phase hypertension: the
      West Birmingham malignant hypertension project.
AB  - Patients with malignant hypertension (MHT) have persistent vascular dysfunction
      and a much worse clinical prognosis than non-MHT hypertensive patients, despite
      good long-term blood pressure (BP) control. We hypothesized that abnormal
      arterial (arterial elastance (Ea); arterial elastance index (EaI)) and
      ventricular (End-systolic elastance (Ees) and End-diastolic elastance (Eed))
      elastances are present in treated MHT patients, compared with non-MHT
      hypertensive controls. Echocardiographic parameters of cardiac and vascular
      stiffness (EaI, Ees and Eed) were quantified in patients with stable MHT and
      treated 'high-risk' hypertension patients (HHT, but non-MHT). All patients had
      well-controlled BP, with a median follow-up time for MHT of 144 months. Ea was
      calculated from stroke volume and systolic BP and adjusted by body area (EaI).
      Ees was calculated using systolic and diastolic BP, stroke volume, ejection
      fraction, time intervals and estimated normalized ventricular elastance at
      arterial end diastole. Eed was calculated from Doppler parameters and the
      diastolic filling volume. Both study groups had preserved left ventricular
      contractility, with no significant differences on 3D-echocardiography (P=0.10)
      There were no significant differences in EaI (P=0.83), Ees (P=0.32), Eed (P=0.23)
      and arterial-ventricular interaction (Ees/Ea, P=0.69). In the MHT group, Eed
      positively correlated with age (r=0.56, P=0.38) and systolic BP (r=0.68,
      P=0.008). On multivariable regression analysis, MHT status was not predictive of
      the ventricular and Ea. Despite documented vascular dysfunction in patients with
      previously diagnosed stable MHT, the arterial and systolic elastances were
      similar to HHT patients, suggesting that adequate BP control in MHT patients
      allows preservation or restoration of normal arterial-ventricular coupling.

PMID- 22357520
TI  - Structural basis for telmisartan-mediated partial activation of PPAR gamma.
AB  - Telmisartan, a selective angiotensin II type 1 receptor blocker, has recently
      been shown to act as a partial agonist for peroxisome proliferator-activated
      receptor gamma (PPARgamma). To understand how telmisartan partially activates
      PPARgamma, we determined the ternary complex structure of PPARgamma, telmisartan,
      and a coactivator peptide from steroid receptor coactivator-1 at a resolution of
      2.18 A. Crystallographic analysis revealed that telmisartan exhibits an
      unexpected binding mode in which the central benzimidazole ring is engaged in a
      non-canonical--and suboptimal--hydrogen-bonding network around helix 12 (H12).
      This network differs greatly from that observed when full-agonists bind with
      PPARgamma and prompt high-coactivator recruitment through H12 stabilized by
      multiple hydrogen bonds. Binding with telmisartan results in a less stable H12
      that in turn leads to attenuated coactivator binding, thus explaining the
      mechanism of partial activation.

PMID- 22357521
TI  - Physical activity modifies the association between CYBA gene polymorphisms and
      small artery elasticity in a Chinese population.
AB  - Emerging evidence suggests that increased superoxide production is responsible
      for a significant proportion of endothelial dysfunction. The relationship between
      variants of the CYBA gene and cardiovascular diseases is currently debated. In
      the present study, we investigated the influence of CYBA polymorphisms (rs1049255
      and rs7195830) on arterial elasticity in a Chinese population. In the 2178
      participants enrolled in the GaoYou study, we measured large artery elasticity
      (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA
      polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255
      polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31+/
      0.11 vs. 5.52+/-0.06 ml mm Hg(-1) * 100; P=0.01). Further analyses revealed an
      interaction between CYBA polymorphisms and physical activity with respect to C2
      (P=0.007 for rs1049255 and P=0.038 for rs7195830). In less physically active
      participants, the AA genotype of the rs1049255 polymorphism was associated with a
      significantly lower C2 than the GG/AG genotypes (4.69+/-0.16 vs. 5.26+/-0.19 ml
      mm Hg(-1) * 100; P=0.008). In physically active participants, the GG/AG genotypes
      of rs7195830 polymorphism were correlated with higher C2 values than the AA
      genotype (5.84+/-0.08 vs. 5.08+/-0.32 ml mm Hg(-1) * 100; P=0.049). Haplotype
      analyses revealed higher C2 values in rs1049255G-rs7195830G carriers (P=0.0015).
      In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were
      associated with C2 in a Chinese population; physical activity could modify this
      genetic effect.

PMID- 22357522
TI  - Whole-body vibration training reduces arterial stiffness, blood pressure and
      sympathovagal balance in young overweight/obese women.
AB  - Obesity is associated with early cardiovascular dysfunction and reduced muscle
      strength. Whole-body vibration (WBV) training may improve arterial function and
      muscle strength. The effects of WBV training on arterial stiffness (brachial
      ankle pulse wave velocity, baPWV), wave reflection (augmentation index, AIx),
      brachial systolic blood pressure (bSBP), aortic systolic blood pressure (aSBP),
      heart rate variability, and muscle strength (one-repetition maximum, 1RM) were
      examined in 10 young (21 +/- 2 year) overweight/obese women (body mass index, BMI
      = 29.9 +/- 0.8 kg m(-2)). Participants were randomized to a 6-week WBV training
      or non-exercising control (CON) period in a crossover design. WBV training (3
      days * week) consisted of static and dynamic squats and calf raises with
      vibration intensity at 25-30 Hz and 1-2 mm amplitude (2.83-4.86 G). There were
      significant (P<0.05) decreases in baPWV (-0.9 +/- 0.3 m s(-1)), AIx (-8.0 +/- 2.2
      %), bSBP (-5.3 +/- 1.5 mm Hg), aSBP (-5.2 +/- 2.1 mm Hg), low-frequency power (
      0.13 +/- 0.05 nu) and sympathovagal balance (LF/HF, -0.42 +/- 0.16) after WBV
      training compared with CON. Significant (P<0.05) increases in high-frequency
      power (HF, 0.19 +/- 0.04 nu) and leg extension 1RM (8.2 +/- 2.3 kg) occurred
      after WBV training compared with CON. Six weeks of WBV training decreased
      systemic arterial stiffness and aSBP via improvements in wave reflection and
      sympathovagal balance in young overweight/obese normotensive women. WBV training
      may benefit arterial function and muscle strength in deconditioned individuals
      who cannot perform conventional exercise.

PMID- 22357523
TI  - Diagnostic accuracy of home vs. ambulatory blood pressure monitoring in untreated
      and treated hypertension.
AB  - Several studies with relatively small size and different design and end points
      have investigated the diagnostic ability of home blood pressure (HBP). This study
      investigated the usefulness of HBP compared with ambulatory monitoring (ABP) in
      diagnosing sustained hypertension, white coat phenomenon (WCP) and masked
      hypertension (MH) in a large sample of untreated and treated subjects using a
      blood pressure (BP) measurement protocol according to the current guidelines. A
      total of 613 subjects attending a hypertension clinic (mean age 53+/-12.4 (s.d.)
      years, men 57%, untreated 59%) had measurements of clinic BP (three visits,
      triplicate measurements per visit), HBP (6 days, duplicate morning and evening
      measurements) and awake ABP (20-min intervals) within 6 weeks. Sustained
      hypertension was diagnosed in 50% of the participants by ABP and HBP (agreement
      89%, kappa=0.79), WCP in 14 and 15%, respectively (agreement 89%, kappa=0.56) and
      MH in 16% and 15% (agreement 88%, kappa=0.52). Only 4% of the subjects (27/613)
      showed clinically significant diagnostic disagreement with BP deviation >5 mm Hg
      above the diagnostic threshold (for HBP or ABP). By taking ABP as reference, the
      sensitivity, specificity, positive and negative predictive value of HBP in
      detecting sustained hypertension were 90, 89, 89 and 90%, respectively, WCP 61,
      94, 64 and 94% and MH 60, 93, 60 and 93%. Similar diagnostic agreement was found
      in untreated and treated subjects. HBP appears to be a reliable alternative to
      ABP in the diagnosis of hypertension and the detection of WCP and MH in both
      untreated and treated subjects.

PMID- 22357524
TI  - Exaggerated blood pressure response during exercise treadmill testing: functional
      and hemodynamic features, and risk factors.
AB  - The factors which contribute to an exaggerated blood pressure response (EBPR)
      during the exercise treadmill test (ETT) are not wholly understood. The
      association between the insertion/deletion polymorphisms of the angiotensin
      converting enzyme (ACE) and M235T of the angiotensinogen with EBPR during ETT
      still remains unstudied. To identify and compare the risk factors for
      hypertension between normotensive subjects with EBPR and those who exhibit a
      normal curve of blood pressure (BP) during ETT. In a series of EBPR cases from a
      historical cohort of normotensive individuals, a univariate analysis was
      performed to estimate the association of the studied factors with BP behavior
      during ETT. Additionally, logistic multivariate regression was conducted to
      analyze the joint effects of the variables. P-values above 0.05 were considered
      statistically significant. From a total of 10,027 analyzed examinations, only 219
      met the criteria employed to define EBPR, which resulted in a prevalence of
      12.6%. For the systolic component of the BP, hyperreactive subjects displayed a
      mean age and body mass index (BMI) significantly higher than the others (P=0.002
      and <0.001, respectively). No association was observed between the polymorphisms
      cited above and EBPR. An analysis of the joint effect of variables has indicated
      that only age (P< 0.001) and BMI (P=0.001) were specifically associated with
      systolic BP during exercise. Age and BMI were the only factors that independently
      influenced EBPR during ETT.

PMID- 22357525
TI  - [Association between occupational stress and musculoskeletal disorders in lower
      extremity].
AB  - OBJECTIVE: To explore the relationship between occupational stress and
      musculoskeletal disorders in lower extremity. METHODS: The cross-sectional study
      was used to investigate 5338 workers in 13 factories and companies for prevalence
      of musculoskeletal disorders in lower extremity, working postures and
      occupational stress were investigated with questionnaires for past year.
      Perceived occupational stress was evaluated by the Chinese version of the Job
      Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) Model
      Questionnaire. Logistic regression analyses were conducted to estimate the
      associations between occupational stress and prevalence of musculoskeletal
      disorders in lower extremity. RESULTS: In the main dimensions of job strain and
      ERI model, physical demands and effort were risk factors of hip disorders, but
      job control was a protective factor of hip disorders. When job strain and ERI
      model scales were analyzed simultaneously, only physical demands were risk factor
      of hip disorders. When job strain and the effort-reward imbalance were computed
      by creating four independent categories, job strain was a risk factor of hip
      disorders, ERI was a risk factor of hip and knee disorders. The risk of imbalance
      between job strain and effort-reward the protective effect of job control
      increased with the disorder regions. According to continuous variable analysis,
      job strain by calculated with physical demands was risk factor of hip disorders,
      continuous ERI variable was risk factor of hip and knee disorders. CONCLUSION:
      Occupational stress is associated significantly with musculoskeletal disorders in
      lower extremity. The control of occupational stress and increase of job control
      should be considered for preventing the musculoskeletal disorders in lower
      extremity.

PMID- 22357526
TI  - [Gender difference of relationship between occupational stress and depressive
      symptoms].
AB  - OBJECTIVE: To explore gender difference of relationship between occupational
      stress and depressive symptoms. METHODS: The cross-sectional study was used to
      investigate 5338 workers in 13 factories and companies, the depressive symptoms
      were assessed with Epidemiologic Studies Depression Scale (CES-D) and the
      perceived occupational stress was evaluated by the Chinese version of the Job
      Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) Model
      Questionnaire. Logistic regression analyses were conducted to estimate the
      associations between occupational stress and prevalence of depressive symptoms.
      RESULTS: Prevalence of depressive symptoms was 31.8% for all subjects, 33.8% for
      males and 27.7% for females, gender difference of prevalence was significant (P <
      0.01). Psychological demands, physical demands, job control, effort,
      overcommitment and negative affectivity scores for males were significantly
      higher than those for females(P < 0.01 or 0.05), social support, reward and job
      satisfaction scores for males were significantly lower than those for females (P
      < 0.01). Psychological demands, physical demands, job control, effort,
      overcommitment and negative affectivity scores for workers with depressive
      symptoms were significantly higher than those for workers without depressive
      symptoms (P < 0.01) but job control, social support, reward, job satisfaction and
      positive affectivity scores for workers with depressive symptoms were
      significantly lower than those for without depressive symptoms (P < 0.01).
      Psychological demands, physical demands, job control, effort, overcommitment and
      negative affectivity scores for male workers with depressive symptoms were
      significantly higher than those for female counterparts (P < 0.01), but social
      support, reward, job satisfaction scores for male workers with depressive
      symptoms were significantly lower than hose for female workers with depressive
      symptoms (P < 0.01). Ratio of male workers and male workers with depressive
      symptoms with job strain and ERI > 1, high demands and low control, and high
      effort and low reward were higher than female counterparts (P < 0.01). The risk
      of depressive symptoms for female with high demands and low control was about two
      times as high as that for female workers with low demands and high control for
      psychological demands and physical demands (OR = 2.0), risk for females was
      slightly higher than that for males (OR = 2.04 and 2.17, respectively). The risk
      of depressive symptoms for workers with high efforts and low rewards was about
      two times as high as that for workers with low efforts and high rewards (OR =
      1.70). No interactive effect between gender and job strain and ERI on depressive
      symptoms were found. CONCLUSION: The gender difference of relationship between
      depressive symptom prevalence and job strain may due to the difference of
      psychosocial factors between females and males. There may be no interactive
      effect between psychosocial factors and gender on depressive symptoms.

PMID- 22357527
TI  - [Relationship between job satisfaction and occupational stress in the workers of
      a thermal power plant].
AB  - OBJECTIVE: To explore the relationship between job satisfaction and occupational
      stress in the workers of a thermal power plant. METHODS: The cluster sampling
      method was used to investigate 875 workers in a thermal power plant. The job
      satisfaction, occupational stressors, strains, personalities, meeting strategy
      and social support were measured using occupational stress instruments, job
      content questionnaire and effort-reward imbalance questionnaire. RESULTS: There
      were no significant differences of job satisfaction scores between different
      groups according to sex, educational level, marriage status, smoking and drinking
      (P > 0.05). But there were significant differences of job satisfaction scores
      between different age groups or between different service length groups (P <
      0.01). The correlation analysis revealed that job satisfaction scores were
      related positively to responsibility for persons and things, promotion
      opportunity, job control, job stabilization, rewards, mental health, positive
      affectivity, self-esteem, superior support and coworker support scores (P < 0.05
      or P < 0.01), negatively to role ambiguity and conflict, job future ambiguity,
      job demands, negative affectivity, depressive symptoms, patience, and mental
      locus of work control(P < 0.05 or P < 0.01). The results of variance analysis
      indicated that the job relationship, responsibility for persons and things,
      promotion opportunity, job control, job stabilization, reward, mental health,
      positive affectivity, self-esteem and buffer scores of the workers with high job
      satisfaction scores were significantly higher than those of workers with moderate
      and lower job satisfaction scores (P < 0.01), but the role ambiguity and
      conflict, job future ambiguity, job demands, and depressive symptoms scores and
      mental locus of work control of the workers with high job satisfaction scores
      were significantly lower than those of workers with moderate and lower job
      satisfaction scores (P < 0.05 or P < 0.01). The results of multivariate logistic
      regression analysis showed that the risk of job dissatisfaction for workers with
      low reward was about four times as high as that for workers with high reward (OR
      = 3.773), the risks of job dissatisfaction for workers with low social support
      and mental locus of external work control were about two times as high as that
      for workers with high social support or mental locus of internal work control (OR
      = 2.419 and 2.219, respectively). The daily life stress, low control strategy,
      low support strategy, low job control and negative affectivity were risk factors
      of job dissatisfaction (OR = 1.125 approximately 1.790), but the self-esteem and
      positive affectivity could reduce the risk of job dissatisfaction. CONCLUSION:
      Increasing the decision level, social support, meeting strategy and reward or
      decreasing the role conflict and ambiguity, demands and negative affectivity
      could improve worker's job satisfaction level.

PMID- 22357528
TI  - [The relationship between occupational stress and serum glycosylated hemoglobin
      A1c level].
AB  - OBJECTIVE: To explore the relationship between occupational stress and serum
      glycosylated hemoglobin A1c (HbA1c) level. METHODS: A cross-sectional
      epidemiological study was conducted in 115 dispatchers. The occupational
      stressors, personality, occupational strain and coping with stress were measured
      using Occupational Stress Instrument. Serum HbA1c levels were measured by
      stratigraphic analysis of cation exchange resin. RESULTS: Serum HbA1c level
      (6.63% +/- 1.93%) in the shiftwork group was significantly higher than that
      (5.73% +/- 1.57%) in the daily relay work group (P < 0.05). Spearman correlation
      analyses showed the positive correlation between type A behavior and serum HbA1c
      level (r = 0.221), the negative correlation between organizational commitment and
      serum HbA1c level (r = -0.218). Variance analyses revealed that serum HbA1c
      levels among high, middle and low job requirement groups and job control groups
      were significantly different (P < 0.05). There were significant differences of
      serum HbA1c levels among different type A behavior, internal control,
      susceptibility of stress and organizational commitment groups (P < 0.05).
      Stepwise regression analyses indicated that shiftwork affects obviously serum
      HbAlc level, internal control and job future were the predictors of serum HbA1c
      level (R2 = 0.082). CONCLUSION: Serum HbA1c may be a potential biomarker in field
      investigation of the effects of occupational stress.

PMID- 22357529
TI  - [Associations of GR and ACTHR gene polymorphisms with quantitative trait of
      strain].
AB  - OBJECTIVE: To explore association between GR and ACTHR gene polymorphisms and
      quantitative trait of stress in Chinese Han population. METHODS: Four polymorphic
      markers (GRA5556G, A5556G, GAGG4534/4536AAAG, promoter T-2C) in GR gene and ACTHR
      gene were genotyped with PCR-RLFP in 200 healthy Hans. ISTA6.0 and life event
      stressor questionnaire was used to assess stressors. JSS, SCL-90 and GWB
      questionnaires were used to quantify the phenotypes of stress. Blood cortical and
      ACTH levels, and nervous behavior function were measured to assess Physiological
      strain. CWAI questionnaire was used to assess work ability. Then strain was
      assessed with Structural equation modeling (SEM). RESULTS: The subjects with GR
      A5556G genotype (G/A) showed significantly higher plasma cortisol levels, higher
      psychological stress scores, lower work ability scores and lower plasma ACTH
      levels compared with the subjects with wild-type (P < 0.01). Psychological stress
      scores and plasma cortisol levels in the subjects with GR GAGG4534/4536AAAG AG
      genotype were significantly higher than those in the subjects with wild-type, but
      the reaction and action sensitivity in the subjects with GR GAGG4534/4536AAAG AG
      genotype were significantly lower than those in ones with wild-type (P < 0.01).
      The ACTH level in the subjects with ACTHR promoter T-2C T/T genotype was
      significantly lower than that in ones with C/C and C/T genotype (P < 0.01).
      Interaction of GRA5556G and GG4534/4536AAAG with plasma cortisol was positively
      associated (betas = 0.543, P < 0.01), but with SCL-90 score was negatively
      associated (betas = -0.374, P < 0.01). Interaction of GRA5556G and GGC6294G with
      plasma cortisol was correlated (betas = 0.465, P < 0.05). While GR and ACTHR gene
      variants are the risk factors for psychological strain, physiological strain and
      decreased work ability (betas are 0.62, 0.43, -0.74, respectively (P < 0.01).
      While scarce social support, job stressors, negative life stressors and dangerous
      individual characters are the risk factors for occupational strain, psychological
      strain, physiological strain and decreased work ability (P < 0.01). CONCLUSION:
      GRA5556G, GRA5556G, GAGG4534/4536AAAG and ACTHR promoter T-2C variants might be
      associated with quantitative trait of strain, and GR and ACTHR gene variants with
      stressors increased the risk for developing strain.

PMID- 22357530
TI  - [Development of China Musculoskeletal Questionnaire and item selection].
AB  - OBJECTIVE: To develop a draft questionnaire (China Musculoskeletal Questionnaire,
      CMQ) for evaluating of musculoskeletal workload and associated potential
      hazardous working conditions as well as musculoskeletal symptoms of workers in
      Sitting Posture. METHODS: Multi-methods, which include the reviewing references,
      the summarizing results of preliminary studies, the reviewing ergonomic tools,
      the consulting experts and occupational health workers and the interviewing or
      discussing with individual workers in sitting posture, were used in developing
      item pool. The experts and epidemiologists of occupational health scored the
      importance of every single item in the item pool, and then the survey and
      sampling were carried out in 325 workers of sitting posture who completed the
      questionnaire. On the basis of these data, the methods including experts scoring,
      item analysis, Cronbach's alpha analysis and factor analysis were synthetically
      used to select the reliable items which consisted of the formal questionnaire.
      RESULTS: The standard of the CMQ, which consists of 34 items on musculoskeletal
      workload and associated potentially hazardous working conditions, can be divided
      into nine indices (dynamic loads, static loads, repetitive loads, forces
      exertion, prolong time, climatic factors, vibration, position and ergonomic
      environmental factors). CONCLUSION: The CMQ possesses good content validity, and
      the items of CMQ are divergent, reliable and typical. However, the reliability
      and validity of CMQ should be validated.

PMID- 22357531
TI  - [The relationship between single nucleotide polymorphisms of JWA gene and
      susceptibility to hypertension in workers exposed to heat stress].
AB  - OBJECTIVE: To study the relationship between JWA polymorphisms and the
      susceptibility to hypertension in workers exposed to heat stress. METHODS: The
      exposure group included 158 steelworkers and rollers and 76 workers unexposed to
      heat stress served as control group. The general information was collected
      according to a questionnaire and the blood pressure was examined for all
      subjects. The polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) technique was used to analyze the site 76 in promoter and site 723 in
      the 3rd exon of JWA gene in the peripheral lymphocytes. PHASE 2.0 software was
      utilized to calculate the haploid type. RESULTS: In the exposure group, JWA76 G/G
      genotype frequencies of sub-group with normal blood pressure, sub-group with
      higher blood pressure and sub-group with hypertension were 82.35%, 69.70% and
      65.00%, respectively, there were significant differences among 3 sub-groups (P <
      0.05). JWA 76 G/G genotype frequencies decreased with blood pressure (chi2 =
      4.86, P = 0.027). The multiple logistic regression analysis showed that the
      subjects with G/C genotype were compared to the subjects with G/G genotype in the
      exposure group, the adjusted OR value was 3.67 (95%CI: 1.21 approximately 11.05)
      for the risk of hypertension and higher blood pressure. the subjects with GG/CT
      haploid type were compared to the subjects with non-GG/CT haploid type in the
      exposure group, the adjusted OR values for the risks of hypertension and higher
      blood pressure were 8.30 (1.39 approximately 49.44) and 8.55 (1.53 approximately
      47.48), respectively. CONCLUSION: The gene polymorphisms at site 76 and GG/CT
      haploid type of JWA gene were associated with hypertension in workers exposed to
      high temperature.

PMID- 22357532
TI  - [The differential expression of Stathmin in the spinal cord tissue of hens
      exposed to tri-o-cresyl phosphate].
AB  - OBJECTIVE: To screen the differently expressed proteins related to regulating the
      depolymerization of microtubules in the spinal cord of hens exposed to tri-o
      cresyl phosphate (TOCP) and to provide target protein evidence for exploring the
      mechanisms of the delayed neurotoxicology (OPIDN) induced by organophosphorus
      compounds (OPs). METHODS: Forty two Roman hens were randomly divided into three
      groups, i.e. TOCP group treated with 1000 mg/kg TOCP; intervention group treated
      with 40 mg/kg phenylmethanesulfonyl fluoride (PMSF) before 1000 mg/kg TOCP
      treatment and control group treated with tap water. Four hens in each group were
      sacrificed on the 5th and 20th days after exposure, respectively. Spinal cords
      were separated and homogenates at low temperature, and the total proteins were
      extracted. The OPIDN symptoms observed and recorded in the remaining 6 hens in
      each group. The differently expressed proteins related to regulating the
      depolymerization of microtubules were screen by two-dimensional electrophoresis
      and mass spectroscopy (MS). RESULTS: The OPIDN symptoms appeared on the 5th day
      after exposure in TOCP group, which were gradually serious with time. The results
      by two-dimensional electrophoresis and MS showed that the Stathmin expression was
      downregulated 3.4 times and 2.8 times in TOCP group, respectively, as compared
      with the control and PMSF intervention groups. However, there was no significant
      difference of the Stathmin expression between control group and PMSF intervention
      group. CONCLUSION: The Stathmin expression in the spinal cord tissues of hens
      exposed to TOCP significantly downregulated. Moreover, the downregulated Stathmin
      expression may be related to excess polymerization of microtubules and the
      mechanism of OPIDN.

PMID- 22357533
TI  - [Association between SNPs in SOD1 and noise-induced hearing loss in Chinese Han
      population].
AB  - OBJECTIVE: To observe the association between SNPs in SOD1 (rs1041740, rs2070424,
      rs10432782 and rs4998557) and noise-induced hearing loss in Chinese Han
      population. METHODS: A case-control study was used to study the effects of
      environmental risk factors on the susceptibility to noise induced hearing loss
      (NIHL) in 201 sensitive workers and 202 resistant workers. A questionnaire was
      designed to carry out an investigation, and an occupational health survey was
      used to identify the occupational risk factors. Genomic DNA was extracted from
      peripheral blood cells using standard procedures of Takara kit, and 5 ml blood
      was from each subject. SNPs were detected using standard procedures of TaqMan
      probe allele identification method. RESULTS: In SOD1 gene, the A allele of
      rs2070424 was a protective factor of NIHL, compared with the G allele (OR = 0.67,
      95%CI: 0.50 approximately 0.88). The risk with NIHL in subjects with AA genotype
      was significantly lower than that in subjects with GG genotype (OR = 0.48, 95%CI:
      0.26 approximately 0.79). After adjusting the confusion factors, OR was 0.44 and
      95%CI was 0.25 approximately 0.78. CONCLUSION: In Chinese Han population, the SNP
      of rs2070424 in SOD1 may be associated with the susceptibility to NIHL.

PMID- 22357534
TI  - [Effect of DNA polymerase beta on apoptosis and mitochondrial membrane potential
      induced by hydroquinone, a metabolite of benzene].
AB  - OBJECTIVE: To explore the effect and mechanism of DNA polymerase beta expression
      level on cell apoptosis and mitochondrial membrane potential induced by
      hydroquinone. METHODS: Polbeta wild-type cells (polbeta+/+), polbeta
      overexpressed cells (polbeta oe) and polbeta null cells (polbeta-/-) were applied
      as a model cell system, The effect of cell apoptosis and mitochondrial membrane
      potential induced by different doses of hydroquinone were analyzed by flow
      cytometry. The ROS and .OH assay kit were used to examine the cellular ROS and
      .OH level. The activity of cellular SOD and GSH-Px were tested by
      Chemiluminescence method after exposed to different concentrations of
      hydroquinone. RESULTS: With the dose of hydroquinone increased, the rate of
      apoptosis and falling of mitochondrial membrane potential (DeltaPsim) in cells
      were increased compared with the control. When compared with polbeta+/+ cells,
      the rate of apoptosis in polbeta-/- cells exposed to 20.00, 40.00, 80.00 umol/L
      hydroquinone increased and the rate of apoptosis in polbeta oe cells exposed to
      10.00, 20.00, 40.00, 80.00 umol/L hydroquinone decreased (P < 0.05). Compared
      with polbeta+/+ cells (20.60% +/- 0.57%, 37.95% +/- 0.64%, 44.50% +/- 1.27%,
      57.55% +/- 1.06%), the rate of cell which undergone mitochondrial depolarization
      in polbeta-/- cells treated with 10.00, 20.00, 40.00, 80.00 umol/L hydroquinone
      (33.60% +/- 1.55%, 46.05% +/- 1.77%, 52.75% +/- 2.05%, 75.20% +/- 0.56%)
      increased. The rate of cell which undergone mitochondrial depolarization in
      polbeta oe cells exposed to 10.00, 20.00, 40.00, 80.00 umol/L hydroquinone
      (16.05% +/- 1.20%, 29.80% +/- 1.21%, 35.15% +/- 1.06%, 53.80% +/- 0.85%)
      decreased (P < 0.05). When compared with polbeta+/+ cells, fluorescent intensity
      of polbeta-/- cells treated with different dosages of hydroquinone increased,
      while which of polbeta oe cells decreased (P < 0.05). Compared with polbeta+/+
      cells, .OH level of polbeta-/- cells treated with 20.00, 40.00 umol/L
      hydroquinone significantly enhanced, while which of polbeta oe cells decreased
      sharply (P < 0.05). Under the same concentrations of hydroquinone, the activity
      of SOD and GSH-Px were decreased most rapidly in polbeta-/- cells. The activity
      of SOD and GSH-Px in polbeta oe cells decreased slower than in the polbeta-/-
      cells. CONCLUSION: Hydroquinone could induced apoptosis by the generation of ROS
      and decrease of DeltaPsim; polbeta could protect cells from apoptosis induced by
      hydroquinone through decrease of ROS level and depolarization of mitochondria.

PMID- 22357535
TI  - Impact of erectile function and age in men with lower urinary tract symptoms on
      ejaculatory dysfunction and premature ejaculation.
AB  - Lower urinary tract symptoms (LUTSs) and ED are clearly correlated, but to date
      no correlation with ejaculatory dysfunction (EjD) has been identified. Therefore,
      this study evaluated the impact of erectile function in men with LUTS on EjD and
      premature ejaculation (PE). Erectile function, PE and EjD of 239 men (mean age,
      53.0 +/- 10.65 years), International Prostate Symptom Score (IPSS), International
      Index of Erection Function (IIEF), intravaginal ejaculatory latency time (IELT)
      and the seven-item Male Sexual Health questionnaire (MSHQ)-EjD were used to
      compare with the degree of LUTS. Ages were divided into five groups (<40, 40-49,
      50-59, 60-69 and >70 years). The IPSS categorized patients into three symptom
      groups: mild, 1-7; moderate, 8-19; and severe, >19. ED was classified into five
      categories based on IIEF-EF scores: severe (0-6), moderate (7-12), mild-to
      moderate (13-18), mild (19-24) and normal (25-30). The correlations among age,
      IIEF-EF, IELT and the MSHQ-EjD domain were studied through regression and cross
      tabulation analyses. The results revealed that aging significantly affected each
      item of the MSHQ-EjD (P<0.05). The IIEF-EF domain was also correlated with each
      question on the MSHQ-EjD (P<0.05). PE (IELT <1 min) increased in incidence as
      patients got older but was not linked to IIEF-EF (P>0.05). These results indicate
      that EjD is closely related to age and erectile function, and that PE is closely
      related to age, although PE is not related to erectile function.

PMID- 22357536
TI  - Recalibrating intellectual property rights to enhance translational research
      collaborations.
AB  - Multisectoral collaborative models for drug and therapeutic research and
      development (R&D) are emerging, requiring a recalibration of how intellectual
      property rights (IPRs) are used. Although these models appear promising, little
      study has been conducted on the optimal blend of sharing and exclusion as
      mediated through the proactive use or nonuse of IPRs. This Commentary is a call
      for a combination of theoretical and empirical analyses to build a comprehensive
      understanding of the interplay between formal IP laws, institutions that
      administer and manage IPRs, and the use of IPRs in practice to better construct
      and manage collaborations. Such analyses require outcome metrics formulated to
      measure the success of therapeutic outcomes and to capture the complexity of a
      highly networked R&D environment.

PMID- 22357537
TI  - MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented
      expansion.
AB  - Identification and treatment of abdominal aortic aneurysm (AAA) remains among the
      most prominent challenges in vascular medicine. MicroRNAs are crucial regulators
      of cardiovascular pathology and represent possible targets for the inhibition of
      AAA expansion. We identified microRNA-21 (miR-21) as a key modulator of
      proliferation and apoptosis of vascular wall smooth muscle cells during
      development of AAA in two established murine models. In both models (AAA induced
      by porcine pancreatic elastase or infusion of angiotensin II), miR-21 expression
      increased as AAA developed. Lentiviral overexpression of miR-21 induced cell
      proliferation and decreased apoptosis in the aortic wall, with protective effects
      on aneurysm expansion. miR-21 overexpression substantially decreased expression
      of the phosphatase and tensin homolog (PTEN) protein, leading to increased
      phosphorylation and activation of AKT, a component of a pro-proliferative and
      antiapoptotic pathway. Systemic injection of a locked nucleic acid-modified
      antagomir targeting miR-21 diminished the pro-proliferative impact of down
      regulated PTEN, leading to a marked increase in the size of AAA. Similar results
      were seen in mice with AAA augmented by nicotine and in human aortic tissue
      samples from patients undergoing surgical repair of AAA (with more pronounced
      effects observed in smokers). Modulation of miR-21 expression shows potential as
      a new therapeutic option to limit AAA expansion and vascular disease progression.

PMID- 22357539
TI  - The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron
      shuttle to grow at oxic-anoxic interphases.
AB  - Faecalibacterium prausnitzii is one of the most abundant bacteria in the human
      gut ecosystem and it is an important supplier of butyrate to the colonic
      epithelium. Low numbers of faecalibacteria have been associated with inflammatory
      bowel disease. Despite being extremely oxygen sensitive, F. prausnitzii is found
      adherent to the gut mucosa where oxygen diffuses from epithelial cells. This
      paradox is now explained on the basis of gas tube experiments, flavin-dependent
      reduction of 5,5'-dithiobis-2-nitrobenzoate and microbial fuel cell experiments.
      The results show that F. prausnitzii employs an extracellular electron shuttle of
      flavins and thiols to transfer electrons to oxygen. Both compounds are present in
      the healthy human gut. Our observations may have important implications for the
      treatment of patients with Crohn's disease, for example, with flavin- or
      antioxidant rich diets, and they provide a novel key insight in host-microbe
      interactions at the gut barrier.

PMID- 22357538
TI  - Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA
      damage response functions.
AB  - Breast cancer is the most common cancer in women in developed countries and has a
      well-established genetic component. Germline mutations in a network of genes
      encoding BRCA1, BRCA2, and their interacting partners confer hereditary
      susceptibility to breast cancer. Abraxas directly interacts with the BRCA1 BRCT
      (BRCA1 carboxyl-terminal) repeats and contributes to BRCA1-dependent DNA damage
      responses, making Abraxas a candidate for yet unexplained disease susceptibility.
      Here, we have screened 125 Northern Finnish breast cancer families for coding
      region and splice-site Abraxas mutations and genotyped three tagging single
      nucleotide polymorphisms within the gene from 991 unselected breast cancer cases
      and 868 female controls for common cancer-associated variants. A novel
      heterozygous alteration, c.1082G>A (Arg361Gln), that results in abrogated nuclear
      localization and DNA response activities was identified in three breast cancer
      families and in one additional familial case from an unselected breast cancer
      cohort, but not in healthy controls (P = 0.002). On the basis of its exclusive
      occurrence in familial cancers, disease cosegregation, evolutionary conservation,
      and disruption of critical BRCA1 functions, the recurrent Abraxas c.1082G>A
      mutation connects to cancer predisposition. These findings contribute to the
      concept of a BRCA-centered tumor suppressor network and provide the identity of
      Abraxas as a new breast cancer susceptibility gene.

PMID- 22357541
TI  - The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer:
      de-regulation of mitochondrial genes may be involved.
AB  - Although human papillomavirus (HPV) infection is the main causal factor for
      cervical cancer (CC), there are data suggesting that genetic factors could
      modulate the risk for CC. Sibling studies suggest that maternally inherited
      factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA)
      polymorphisms are associated to CC, HPV infection and HPV types, a case-control
      study was performed in the Mexican population. Polymorphism of mtDNA D-loop was
      investigated in 187 CC patients and 270 healthy controls. HPV was detected and
      typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed
      in a subset of 45 tumor biopsies using the expression microarray ST1.0. The
      Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95%
      confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2
      1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In
      cases, the distribution of HPV types was similar in all haplogroups but one (D1),
      in which is remarkable the absence of HPV18, a very low frequency of HPV16 and
      high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes
      (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK))
      could be involved in the increased risk conferred by the haplogroup B2, as they
      were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the
      association of mtDNA with CC and HPV infection is clear, other studies with
      higher sample size will be needed to elucidate the role of mtDNA in cervical
      carcinogenesis.

PMID- 22357542
TI  - Family history of von Hippel-Lindau disease was uncommon in Chinese patients:
      suggesting the higher frequency of de novo mutations in VHL gene in these
      patients.
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome
      caused by germline mutations in VHL tumor suppressor gene. It is characterized by
      hemangioblastoma in central nervous system and retina, renal cell carcinoma or
      cyst, pheochromocytoma, pancreatic cyst and tumor, endolymphatic-sac tumor, and
      papillary cystadenoma in epididymis and broad ligament. Here, we used PCR-direct
      sequencing and universal primer quantitative fluorescent multiplex PCR (UPQFM
      PCR) to detect VHL mutations in 16 patients clinically diagnosed with VHL
      disease. PCR-direct sequencing detected 12 germline mutations (75%, 12/16), in
      which a novel mutation of c.451A>T/p.Ile151Phe found in one proband had not been
      reported previously. UPQFM-PCR found two large deletions (12.5%, 2/16). The two
      remaining patients carried non-typical disease-causing mutations, including one
      silent mutation (c.481C>A/p.Arg161Arg) and one mutation in 3'-UTR (c.642+70C>A).
      Remarkably, 56.3% (9/16) probands did not have family history of VHL disease,
      suggesting the higher frequency of de novo mutations in Chinese patients. We also
      summarized Chinese VHL disease patients with VHL mutation findings published in
      the literature to provide information about the spectrum of VHL mutations in
      Chinese VHL disease patients.

PMID- 22357543
TI  - DAN (NBL1) specifically antagonizes BMP2 and BMP4 and modulates the actions of
      GDF9, BMP2, and BMP4 in the rat ovary.
AB  - Although differential screening-selected gene aberrative in neuroblastoma (DAN,
      official symbol NBL1) is the founding member of the DAN subfamily of bone
      morphogenetic protein (BMP) antagonists, its antagonizing targets, gene
      regulation, and physiological functions remain unclear. Using diverse cell
      expression systems, we found that the generation of bioactive DAN is likely to be
      cell type specific. Unlike other phylogenetically close members, which are
      covalently linked homodimers, DAN forms a noncovalently linked homodimer during
      folding. Purified recombinant DAN specifically blocked signaling of BMP2 and BMP4
      but not that of other ovarian-expressed transforming growth factor-beta members.
      Although widely distributed in many organs, DAN transcript level was periodically
      regulated by gonadotropins. Ovarian microdissection indicated that NBL1 (DAN)
      mRNA is mainly expressed in granulosa cells, where its transcript level is up
      regulated by the gonadotropin-driven cAMP cascade. We further investigated the
      local regulation and ovarian functions of DAN. NBL1 (DAN) mRNA expression in
      granulosa cells was up-regulated by oocyte-derived growth differentiation factor
      9 (GDF9), whereas treatment with DAN significantly reversed the inhibitory effect
      of BMP4 on follicle-stimulating hormone-induced progesterone production in
      cultured granulosa cells. Our findings suggest the DAN gradient in granulosa
      cells, established by oocyte-derived GDF9, may serve as an antagonist barrier
      that modulates the actions of theca-derived BMP4 and granulosa/theca-derived BMP2
      during folliculogenesis both spatially and temporally.

PMID- 22357544
TI  - Revealing the hidden mechanisms of smoke-induced fallopian tubal implantation.
AB  - Ectopic pregnancy (EP) is an enigmatic reproductive disorder. Although tubal EP
      is difficult to predict, several hypotheses about its etiology have been
      proposed. In retrospective case-control studies, smoking is associated with an
      increased rate of EPs in the fallopian tube. Studies of experimental animals in
      vivo and human fallopian tubal tissues in vitro have suggested mechanisms of
      fallopian tubal damage and dysfunction induced by nicotine and other smoking
      related chemicals that may explain this association. However, the pathogenesis of
      smoking-induced modulation of implantation leading to tubal EP is largely
      unknown. Because cigarette/tobacco smoke adversely affects the success of
      intrauterine implantation, there is a great need to determine how embryo
      implantation occurs in the fallopian tube in female smokers of reproductive age.

PMID- 22357545
TI  - NLRP5 mediates mitochondrial function in mouse oocytes and embryos.
AB  - Unraveling molecular pathways responsible for regulation of early embryonic
      development is crucial for our understanding of female infertility. Maternal
      determinants that control the transition from oocyte to embryo are crucial
      molecules that govern developmental competence of the newly conceived zygote. We
      describe a series of defects that are triggered by a disruption of maternal
      lethal effect gene, Nlrp5. Previous studies have shown that Nlrp5 hypomorph
      embryos fail to develop beyond the two-cell stage. Despite its importance in
      preimplantation development, the mechanism by which the embryo arrest occurs
      remains unclear. We confirmed that Nlrp5 mutant and wild-type females possess
      comparable ovarian germ pool and follicular recruitment rates. However, ovulated
      oocytes lacking Nlrp5 have abnormal mitochondrial localization and increased
      activity in order to sustain physiological ATP content. This results in an
      accumulation of reactive oxygen species and increased cellular stress causing
      mitochondrial depletion. Compromised cellular state is also accompanied by
      increased expression of cell death inducer Bax and depletion of cytochrome c.
      However, neither genetic deletion (Bax/Nlrp5 double knockout) nor mimetic
      interference (BH4 domain or Bax inhibitory peptide) were sufficient to alleviate
      embryo demise caused by depletion of Nlrp5. We therefore conclude that lack of
      Nlrp5 in oocytes triggers premature activation of the mitochondrial pool, causing
      mitochondrial damage that cannot be rescued by inactivation of Bax.

PMID- 22357548
TI  - Peritubular myoid cells from rat seminiferous tubules contain actin and myosin
      filaments distributed in two independent layers.
AB  - In the mammalian testis, peritubular myoid cells (PM cells) surround the
      seminiferous tubules (STs), express cytoskeletal markers of true smooth muscle
      cells, and participate in the contraction of the ST. It has been claimed that PM
      cells contain bundles of actin filaments distributed orthogonally in an
      intermingled mesh. Our hypothesis is that these actin filaments are not forming a
      random intermingled mesh, but are actually arranged in contractile filaments in
      independent layers. The aim of this study is to describe the organization of the
      actin cytoskeleton in PM cells from adult rat testes and its changes during
      endothelin-1-induced ST contraction. For this purpose, we isolated segments of ST
      corresponding to the stages IX-X of the spermatogenic cycle (ST segments), and
      analyzed the actin and myosin filament distribution by confocal and transmission
      electron microscopy. We found that PM cells have actin and myosin filaments
      interconnected in thick bundles (AF-MyF bundles). These AF-MyF bundles are
      distributed in two independent layers: an inner layer toward the seminiferous
      epithelium, and an outer layer toward the interstitium, with the bundles oriented
      perpendicularly and in parallel to the main ST axis, respectively. In endothelin
      1 contracted ST segments, PM cells increased their thickness and reduced their
      length in both directions, parallel and perpendicular to the main ST axis. The AF
      MyF bundles maintained the same organization in two layers, although both layers
      appeared significantly thicker. We believe that this is the first time this
      arrangement of AF-MyF bundles in two independent layers has been shown in smooth
      muscle cells, and that this organization would allow the cell to generate
      contractile force in two directions.

PMID- 22357549
TI  - In vitro transformation of mouse testis cells by oncogene transfection.
AB  - Germ cell tumors (GCTs) are unique in that they exhibit diverse biological
      characteristics and pathological features. Although several in vivo GCT models
      are available, studies on GCTs are hampered because in vivo development of GCTs
      is time consuming and prevents a detailed molecular analysis of the
      transformation process. Here we developed a novel strategy to transform mouse
      testis cells in vitro. Lentivirus-mediated transfection of dominant negative
      Trp53, Myc, and activated Hras1 into a CD9-expressing testis cells caused
      tumorigenic conversion in vitro. Although these cells resembled embryonic stem
      (ES) cells, they were aneuploid and lacked Nanog expression, which is involved in
      the maintenance of the undifferentiated state in ES cells. Euploid ES-like cells
      were produced by transfecting the Yamanaka factors (Pou5f1, Myc, Klf4, and Sox2)
      into the same cell population. Although these cells expressed Nanog, they were
      distinct from ES cells in that they expressed CD44, a cancer stem cell antigen.
      Both treatments induced similar changes in the DNA methylation patterns in
      differentially methylated regions of imprinted genes. Moreover, despite the
      differences in their phenotype and karyotype, both cell types similarly produced
      mixed GCTs on transplantation, which were composed of teratomas, seminomas, and
      embryonal carcinomas. Thus, in vitro testis cell transformation facilitates an
      analysis of the GCT formation process, and our results also suggest the close
      similarity between GCT formation and reprogramming.

PMID- 22357546
TI  - Male germline control of transposable elements.
AB  - Repetitive sequences, especially transposon-derived interspersed repetitive
      elements, account for a large fraction of the genome in most eukaryotes. Despite
      the repetitive nature, these transposable elements display quantitative and
      qualitative differences even among species of the same lineage. Although
      transposable elements contribute greatly as a driving force to the biological
      diversity during evolution, they can induce embryonic lethality and genetic
      disorders as a result of insertional mutagenesis and genomic rearrangement.
      Temporary relaxation of the epigenetic control of retrotransposons during early
      germline development opens a risky window that can allow retrotransposons to
      escape from host constraints and to propagate abundantly in the host genome.
      Because germline mutations caused by retrotransposon activation are heritable and
      thus can be deleterious to the offspring, an adaptive strategy has evolved in
      host cells, especially in the germline. In this review, we will attempt to
      summarize general defense mechanisms deployed by the eukaryotic genome, with an
      emphasis on pathways utilized by the male germline to confer retrotransposon
      silencing.

PMID- 22357547
TI  - The forkhead transcription factor, FOXP3, is required for normal pituitary
      gonadotropin expression in mice.
AB  - The hypothalamic-pituitary-gonadal axis is central to normal reproductive
      function. This pathway begins with the release of gonadotropin-releasing hormone
      in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound
      by receptors on gonadotroph cells in the anterior pituitary gland and stimulates
      the synthesis and secretion of luteinizing hormone and, to some extent, follicle
      stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads
      begin gametogenesis and the synthesis of sex hormones. In humans, mutations of
      the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as
      immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice
      with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are
      infertile. To understand why FOXP3 is required for reproductive function, we are
      investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3(sf/Y)).
      Although the gonadotroph cells appear to be intact in Foxp3(sf/Y) mice,
      luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb)
      expression are significantly decreased, demonstrating that these mice exhibit a
      hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing
      hormone is not significantly decreased in Foxp3(sf/Y) males. Treatment of
      Foxp3(sf/Y) males with a gonadotropin-releasing hormone receptor agonist does not
      rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3
      expression in the pituitary or hypothalamus, suggesting that the infertility seen
      in Foxp3(sf/Y) males is a secondary effect, possibly due to loss of FOXP3 in
      immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and
      prolactin (Prl) are significantly reduced in Foxp3(sf/Y) males, whereas the
      precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is
      increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to
      destruction of the thyroid gland by autoimmune cells. We find that Foxp3(sf/Y)
      mice have elevated expression of thyroid-stimulating hormone beta (Tshb),
      suggesting that they may suffer from thyroiditis as well. Expression of the
      pituitary transcription factors, Pitx1, Pitx2, Lhx3, and Egr1, is normal;
      however, expression of Foxl2 and Gata2 is elevated. These data are the first to
      demonstrate a defect at the pituitary level in the absence of FOXP3, which
      contributes to the infertility observed in mice with Foxp3 loss of function
      mutations.

PMID- 22357550
TI  - Regional differences in smoking, drinking, and physical activities of Chinese
      residents.
AB  - AIMS: This article aims at analyzing regional differences in smoking, drinking,
      and physical activities in China and informing cross-regional initiatives
      addressing these behaviors. METHODS: Data were extracted from available large
      scale surveys. Index of dissimilarity (ID), linear correlation, and geographical
      mapping were used to analyze regional differences in the prevalence of smoking
      (PS), smoking cessation (PSC), regular drinking (PRD), and physical activities
      (PPA). RESULTS: Significant differences existed across regions in all the
      behaviors (P < .01). IDs ranged from 0.04 to 0.42. IDs of PRD and PPA were much
      higher than IDs of PS and PSC. Linear correlation coefficients of the 4
      indicators by regions varied substantially ranging (in absolute value) from 0.031
      to 0.982. Characteristic formats of geographical distribution were found with PS,
      PSC, and PRD and PPA being in "high plateau," "low plateau," and "shifting"
      patterns, respectively. CONCLUSIONS: Distinct regional disparities in health
      behavior exist, and socioculturally and contextually competitive policies and
      interventions are needed.

PMID- 22357551
TI  - Soluble VEGFR-1 in pathophysiology of pregnancies complicated by hypertensive
      disorders: the Indian scenario.
AB  - An imbalance between angiogenic and anti-angiogenic factors has been hypothesized
      to have a major role in hypertensive disorders during pregnancy, which account
      for significant morbidity and mortality for the mother and neonate in India.
      There is a paucity of information on soluble vascular endothelial growth factor
      receptor-1 (sVEGFR-1, anti-angiogenic factor) concentrations in different
      subgroups of pregnancy-induced hypertensive (PIH) disorders particularly in
      gestational hypertension (GH) and eclampsia during pregnancy. This cross
      sectional study was conducted in order to test the above hypothesis and to get
      more insight into the role of sVEGFR-1 in these disorders. The concentrations of
      sVEGFR-1 in serum were measured from women with 22-39 weeks of gestation in the
      control (n=180) and gestationally matched hypertensive (n=360) pregnant mothers
      by ELISA. These sVEGFR-1 concentrations were found to be significantly elevated
      in the study groups as the severity of disease increases from GH to eclampsia (24
      076 pg ml(-1); 42000 pg ml(-1), P=0.0001) as compared with controls (3360 pg ml(
      1)). According to Receiver operating characteristic curve analysis, at <= 34
      weeks, the concentration cutoff, sensitivity, specificity for sVEGFR-1 in
      differentiating GH, pre-eclampsia and eclampsia were >= 7619.2 pg ml(-1), 75%,
      75%; >= 16726.6 pg ml(-1), 89.1%, 89.1%; >= 26222.8 pg ml(-1), 91.6%, 91.6%,
      respectively. The gradual upregulation of sVEGFR-1 concentrations in these groups
      may be due to its intimate involvement in the etiopathogenesis of severity of
      various hypertensive disorders by antagonizing effects of VEGF during the
      placental development. These observations indicate the clinical utility of sVEGFR
      1 in differentiating PIH disorders and also will be helpful for the evaluation of
      increased monitoring system for successful pregnancy.

PMID- 22357552
TI  - Neurological disorders and the potential role for stem cells as a therapy.
AB  - Introduction Neurological disorders are routinely characterized by loss of cells
      in response to an injury or a progressive insult. Stem cells could therefore be
      useful to treat these disorders.  Sources of data Pubmed searches of recent
      literature.  Areas of agreement Stem cells exhibit proliferative capacity making
      them ideally suited for replacing dying cells. However, instead of cell
      replacement therapy stem cell transplants frequently appear to work via
      neurotrophic factor release, immunomodulation and upregulation of endogenous stem
      cells.  Areas of controversy and areas timely for developing research Many
      questions remain with respect to the use of stem cells as a therapy, the answers
      to which will vary depending on the disorder to be treated and mode of action.
      Whereas the potential tumorigenic capability of stem cells is a concern, most
      studies do not support this notion. Further determination of the optimal cell
      type, and whether to perform allogeneic or autologous transplants warrant
      investigation before the full potential of stem cells can be realized. In
      addition, the use of stem cells to develop disease models should not be
      overlooked.

PMID- 22357555
TI  - An automated, parallel processing approach to biomolecular sample preparation.
AB  - Sample preparation for DNA and RNA assays is a prime candidate for laboratory
      automation. A novel, parallel processing device that performs the three separate
      liquid-handling functions necessary for such sample preparation-dispensing,
      pipetting, and pressurizing-is presented. The device comprises an array of fine
      nozzles connected by fluidic channels to automatically and precisely distribute
      flow between one source and an array of points. The design principles, as well as
      the experimental and computational methods used to develop the device, are
      described. Test results, including accuracy, uniformity, volume range, and
      timing, are presented. The functionality of the device is demonstrated by
      performing a solid-phase extraction of DNA with two types of microcolumns.

PMID- 22357553
TI  - Nucleocytoplasmic transport: a role for nonspecific competition in karyopherin
      nucleoporin interactions.
AB  - Nucleocytoplasmic transport occurs through the nuclear pore complex (NPC), which
      in yeast is a ~50 MDa complex consisting of ~30 different proteins. Small
      molecules can freely exchange through the NPC, but macromolecules larger than ~40
      kDa must be aided across by transport factors, most of which belong to a related
      family of proteins termed karyopherins (Kaps). These transport factors bind to
      the disordered phenylalanine-glycine (FG) repeat domains in a family of NPC
      proteins termed FG nups, and this specific binding allows the transport factors
      to cross the NPC. However, we still know little in terms of the molecular and
      kinetic details regarding how this binding translates to selective passage of
      transport factors across the NPC. Here we show that the specific interactions
      between Kaps and FG nups are strongly modulated by the presence of a cellular
      milieu whose proteins appear to act as very weak competitors that nevertheless
      collectively can reduce Kap/FG nup affinities by several orders of magnitude.
      Without such modulation, the avidities between Kaps and FG nups measured in vitro
      are too tight to be compatible with the rapid transport kinetics observed in
      vivo. We modeled the multivalent interactions between the disordered repeat
      binding sites in the FG nups and multiple cognate binding sites on Kap, showing
      that they should indeed be sensitive to even weakly binding competitors; the
      introduction of such competition reduces the availability of these binding sites,
      dramatically lowering the avidity of their specific interactions and allowing
      rapid nuclear transport.

PMID- 22357554
TI  - Target identification by chromatographic co-elution: monitoring of drug-protein
      interactions without immobilization or chemical derivatization.
AB  - Bioactive molecules typically mediate their biological effects through direct
      physical association with one or more cellular proteins. The detection of drug
      target interactions is therefore essential for the characterization of compound
      mechanism of action and off-target effects, but generic label-free approaches for
      detecting binding events in biological mixtures have remained elusive. Here, we
      report a method termed target identification by chromatographic co-elution (TICC)
      for routinely monitoring the interaction of drugs with cellular proteins under
      nearly physiological conditions in vitro based on simple liquid chromatographic
      separations of cell-free lysates. Correlative proteomic analysis of drug-bound
      protein fractions by shotgun sequencing is then performed to identify candidate
      target(s). The method is highly reproducible, does not require immobilization or
      derivatization of drug or protein, and is applicable to diverse natural products
      and synthetic compounds. The capability of TICC to detect known drug-protein
      target physical interactions (K(d) range: micromolar to nanomolar) is
      demonstrated both qualitatively and quantitatively. We subsequently used TICC to
      uncover the sterol biosynthetic enzyme Erg6p as a novel putative anti-fungal
      target. Furthermore, TICC identified Asc1 and Dak1, a core 40 S ribosomal protein
      that represses gene expression, and dihydroxyacetone kinase involved in stress
      adaptation, respectively, as novel yeast targets of a dopamine receptor agonist.

PMID- 22357556
TI  - SiLA: Basic standards for rapid integration in laboratory automation.
AB  - A standard (SiLA, Standardization in Lab Automation) that focuses on the
      connection between sample processing devices and a software system for automation
      gains acceptance. This article reports about the creation and contents of the
      first set of standard specifications developed during the first 2 years. These
      specifications-named Device Control and Data Interface Specification, Common
      Command Dictionary, and Data Capture Specification-describe how devices are
      connected to a software controlling the interplay of the devices, the command
      sets for various device classes, and the structure of result data such as data
      generated by microtiter plate readers. A section about SiLA-compliant products
      and pilot projects using SiLA-compatible devices for system integration gives an
      idea about the acceptance of the standard in the marketplace.

PMID- 22357557
TI  - Concept and validation of a fully automated photocatalytic test setup.
AB  - Photocatalytic activity can be studied by several methods, each with its own
      strengths and weaknesses. To study photocatalytic activity in an easy, user
      friendly, and realistic way, a completely new setup has been built. The setup is
      modularly constructed around Fourier transform infrared spectroscopy (FTIR)
      spectroscopy at the heart of it, resulting in great versatility. Complementary
      software has been written for automatic control of the setup and for processing
      the generated data. Two pollutants, oil and n-octane, are tested to validate the
      performance of the setup. These validation experiments confirm the usefulness and
      added value of the setup in general and of the FTIR detection methodology as
      well. It becomes clear that a system of online measurements with good
      repeatability, accuracy, and user-friendliness has been created.

PMID- 22357558
TI  - A low-cost automated streaming potential measurement system.
AB  - Surface charge characterization is important in the design and testing of
      coatings and membranes for biological and industrial applications, but commercial
      zeta potential meters are expensive and difficult to adapt to a variety of
      membrane designs. We combined inexpensive off-the-shelf components, a test mount
      fabricated with a conventional rapid prototyping system, and software written
      using a no-cost integrated development environment to implement a low-cost,
      automated streaming potential meter. Software written in Visual C# managed a USB
      data acquisition and control pod to regulate the transmembrane pressure while
      simultaneously reading transmembrane voltages from a digital multimeter with 0.1
      nV precision. The streaming potential was measured through a commercially
      available polyethersulfone membrane with repeatable results for transmembrane
      pressures between -15 and 15 kPa. The transmembrane voltages for each set of six
      pressures were linear, with R (2) values greater than 0.9995. The zeta potentials
      calculated from the measured streaming potentials are in agreement with previous
      results for the same commercial membrane previously reported in the literature.
      The material cost for the system is less than $4000.

PMID- 22357559
TI  - PSoC-based embedded design and quartz tuning fork for low-temperature measurement
      system design.
AB  - This article describes a commercial quartz tuning fork (QTF), 8 mm in height by 3
      mm in diameter, holding a two-terminal electronic component with a nominal
      frequency of 32.768 kHz and 12.5 pF typical load capacitance packed in a vacuum
      sealed metal container, which has been used as a sensor for low-temperature
      measurement with good sensitivity, repeatability, and reliability. An embedded
      readout design with the support of a programmable system on-chip (PSoC) and
      virtual instrument control program, which uses a personal computer as an
      input/output device, provides online data acquisition of the QTF frequency data,
      which will in turn provide the measurement of the low-temperature bath in which
      the QTF is immersed. The embedded PSoC readout captures the varying frequency
      signals from the QTF as a response to the measurement temperature, processes it,
      and sends the frequency value to a personal computer, where LabVIEW, a graphical
      language ("G" language), displays the data in a graphical format. The QTFs for
      low temperature (300 K to 77 K) are well studied, whereas a sensor using a PSoC
      embedded design as a readout is a novel design implementation.

PMID- 22357560
TI  - A practical method for patterning lumens through ECM hydrogels via viscous finger
      patterning.
AB  - Extracellular matrix (ECM) hydrogels with patterned lumens have been used as a
      framework to generate more physiologically relevant models of tissues, such as
      vessels and mammary ducts, for biological investigations. However, these models
      have not found widespread use in research labs or in high-throughput screening
      applications in large part because the basic methods for generating the lumen
      structures are generally cumbersome and slow. Here we present viscous finger
      patterning, a technique to generate lumens through ECM hydrogels in microchannels
      that can be accomplished using manual or automated pipetting. Passive pumping is
      used to flow culture media through an unpolymerized hydrogel, creating a lumen
      through the hydrogel that is subsequently polymerized. Viscous finger patterning
      takes advantage of viscous fingering, the fluid dynamics phenomenon where a less
      viscous fluid will flow through and displace a more viscous fluid. We have
      characterized the technique and used it to create a variety of channel geometries
      and ECM hydrogel compositions, as well as for the generation of lumens surrounded
      by multiple hydrogel layers. Because viscous finger patterning can be performed
      with automated liquid handling systems, high-throughput generation of ECM
      hydrogels with patterned lumen is enabled. The ability to rapidly and cost
      effectively create large numbers of lumens in natural polymers overcomes a
      critical barrier to the use of more physiologically relevant tissue models in a
      variety of biological studies and drug screening applications.

PMID- 22357561
TI  - Automation of cell-based drug absorption assays in 96-well format using permeable
      support systems.
AB  - Cell-based drug absorption assays, such as Caco-2 and MDCK-MDR1, are an essential
      component of lead compound ADME/Tox testing. The permeability and transport data
      they provide can determine whether a compound continues in the drug discovery
      process. Current methods typically incorporate 24-well microplates and are
      performed manually. Yet the need to generate absorption data earlier in the drug
      discovery process, on an increasing number of compounds, is driving the use of
      higher density plates. A simple, more efficient process that incorporates 96-well
      permeable supports and proper instrumentation in an automated process provides
      more reproducible data compared to manual methods. Here we demonstrate the
      ability to perform drug permeability and transport assays using Caco-2 or MDCKII
      MDR1 cells. The assay procedure was automated in a 96-well format, including cell
      seeding, media and buffer exchanges, compound dispense, and sample removal using
      simple robotic instrumentation. Cell monolayer integrity was confirmed via
      transepithelial electrical resistance and Lucifer yellow measurements. Proper
      cell function was validated by analyzing apical-to-basolateral and basolateral-to
      apical movement of rhodamine 123, a known P-glycoprotein substrate. Apparent
      permeability and efflux data demonstrate how the automated procedure provides a
      less variable method than manual processing, and delivers a more accurate
      assessment of a compound's absorption characteristics.

PMID- 22357562
TI  - A user-friendly robotic sample preparation program for fully automated biological
      sample pipetting and dilution to benefit the regulated bioanalysis.
AB  - Biological sample dilution is a rate-limiting step in bioanalytical sample
      preparation when the concentrations of samples are beyond standard curve ranges,
      especially when multiple dilution factors are needed in an analytical run. We
      have developed and validated a Microsoft Excel-based robotic sample preparation
      program (RSPP) that automatically transforms Watson worklist sample information
      (identification, sequence and dilution factor) to comma-separated value (CSV)
      files. The Freedom EVO liquid handler software imports and transforms the CSV
      files to executable worklists (.gwl files), allowing the robot to perform sample
      dilutions at variable dilution factors. The dynamic dilution range is 1- to 1000
      fold and divided into three dilution steps: 1- to 10-, 11- to 100-, and 101- to
      1000-fold. The whole process, including pipetting samples, diluting samples, and
      adding internal standard(s), is accomplished within 1 h for two racks of samples
      (96 samples/rack). This platform also supports online sample extraction (liquid
      liquid extraction, solid-phase extraction, protein precipitation, etc.) using 96
      multichannel arms. This fully automated and validated sample dilution and
      preparation process has been applied to several drug development programs. The
      results demonstrate that application of the RSPP for fully automated sample
      processing is efficient and rugged. The RSPP not only saved more than 50% of the
      time in sample pipetting and dilution but also reduced human errors. The
      generated bioanalytical data are accurate and precise; therefore, this
      application can be used in regulated bioanalysis.

PMID- 22357563
TI  - Analysis of base content in in-service oils by fourier transform infrared
      spectroscopy.
AB  - An automated FTIR method for the determination of the base content (BC(pKa)) of
      oils at rates of > 120 samples/h has been developed. The method uses a 5%
      solution of trifluoroacetic acid in 1-propanol (TFA/P) added to heptane-diluted
      oil to react with the base present and measures the nu(COO(-)) absorption of the
      TFA anion produced, with calibrations devised by gravimetrically adding 1
      methylimidazole to a heptane-TFA/P mixture. To minimize spectral interferences,
      all spectra are transformed to 2(nd) derivative spectra using a gap-segment
      algorithm. Any solvent displacement effects resulting from sample miscibility are
      spectrally accounted for by measurement of the changes in the 1-propanol overtone
      band at 1936 cm(-1). A variety of oils were analyzed for BC(0.5), expressed as
      mEq base/g oil as well as converted to base number (BN) units (mg KOH/g oil) to
      facilitate direct comparison with ASTM D2896 and ASTM D974 results for the same
      samples. Linear relationships were obtained between FTIR and D2896 and D974, with
      the ASTM methods producing higher BN values by factors of ~1.5 and ~1.3,
      respectively. Thus, the FTIR BC method correlates well with ASTM potentiometric
      procedures and, with its much higher throughput, promises to be a useful
      alternative means of rapidly determining reserve alkalinity in commercial oil
      condition monitoring laboratories.

PMID- 22357564
TI  - High-content screening data management for drug discovery in a small- to medium
      size laboratory: results of a collaborative pilot study focused on user
      expectations as indicators of effectiveness.
AB  - High-content screening (HCS) technology provides a powerful vantage point to
      approach biological problems; it allows analysis of cell parameters, including
      changes in cell or protein movement, shape, or texture. As part of a
      collaborative pilot research project to improve bioscience research data
      integration, we identified HCS data management as an area ripe for advancement. A
      primary goal was to develop an integrated data management and analysis system
      suitable for small- to medium-size HCS programs that would improve research
      productivity and increase work satisfaction. A system was developed that uses
      Labmatrix, a Web-based research data management platform, to integrate and query
      data derived from a Cellomics STORE database. Focusing on user expectations,
      several barriers to HCS productivity were identified and reduced or eliminated.
      The impact of the project on HCS research productivity was tested through a
      series of 18 lab-requested integrated data queries, 7 of which were fully
      enabled, 7 partially enabled, and 4 enabled through data export to standalone
      data analysis tools. The results are limited to one laboratory, but this pilot
      suggests that through an "implementation research" approach, a network of small-
      to medium-size laboratories involved in HCS projects could achieve greater
      productivity and satisfaction in drug discovery research.

PMID- 22357565
TI  - Process automation toward ultra-high-throughput screening of combinatorial one
      bead-one-compound (OBOC) peptide libraries.
AB  - With an aim to develop peptide-based protein capture agents that can replace
      antibodies for in vitro diagnosis, an ultra-high-throughput screening strategy
      has been investigated by automating labor-intensive, time-consuming processes
      that are the construction of peptide libraries, sorting of positive beads, and
      peptide sequencing through analysis of tandem mass spectrometry data. Although
      instruments for automation, such as peptide synthesizers and automatic bead
      sorters, have been used in some groups, the overall process has not been well
      optimized to minimize time, cost, and efforts, as well as to maximize product
      quality and performance. Herein we suggest and explore several solutions to the
      existing problems with the automation of the key processes. The overall process
      optimization has been done successfully in orchestration with the technologies
      such as rapid cleavage of peptides from beads and semiautomatic peptide
      sequencing that we have developed previously. This optimization allowed one-round
      screening, from peptide library construction to peptide sequencing, to be
      completed within 4 to 5 days. We also successfully identified a 6-mer ligand for
      carcinoembryonic antigen-cell adhesion molecule 5 (CEACAM 5) through three-round
      screenings, including one-round screening of a focused library.

PMID- 22357566
TI  - Dynex: multiplex ELISA technology.
AB  - Conventional enzyme-linked immunosorbent assay (ELISA) is a gold standard for
      screening antibodies and testing for protein or antigen presence. A significant
      limitation of this assay resides in the fact that only one analyte can be
      assessed per microplate well. Here, we describe and investigate a new technology
      consisting of an automated ELISA system in which up to 10 analytes can be
      measured within one single well, thus improving productivity, accuracy, and
      repeatability by reducing the amount of human labor required. Another strength of
      the platform is that a user can load any necessary sets/subsets of beads to
      perform required assays, with improved flexibility compared to manufactured
      loaded arrays for multiplex analysis. We also demonstrate that this system can be
      used to determine the pathogenicity (i.e., presence of Shiga toxins) and serotype
      (i.e., Escherichia coli O157) of E. coli isolates.

PMID- 22357567
TI  - Design of an automated enhanced-throughput platform for functional
      characterization of positive allosteric modulator-induced leftward shifts in
      apparent agonist potency in vitro.
AB  - Prosecution of positive allosteric modulator (PAM) targets demands a specialized
      assay toolset. Many GPCR or ion channel targets are adaptable to functional
      assays whereby PAM efficacy can be inferred from left or rightward shifts in the
      concentration-response curves of orthosteric agonist. The inherent emphasis on
      throughput and occasional paucity of radioligands for a diverse array of
      allosteric modulator targets yields a need for an enhanced throughput agonist
      potency shift assay. Here, we describe a process by which such an assay was
      automated with robust, reproducible in vitro pharmacology. In direct comparison
      with a manual CRC shift assay, the enhanced throughput automated platform
      described here delivered near identical rank orders (r(2) = 0.75) at ~4-fold
      throughput/assay iteration. Correspondingly, average cycle time/plate decreased
      from 104 to 72 minutes. We also observed reductions in assay interference
      associated with compounds exhibiting ago-allosterism, which we attribute to
      preread compound incubation periods which are more precisely time-constrained
      under automation control. By leveraging automated laboratory technology, we have
      achieved meaningful throughput with no sacrifice of precision. Rather than to be
      target-class specific, the present process was specifically designed to serve as
      a platform template for a variety of cell-based functional allosteric modulation
      assays.

PMID- 22357568
TI  - Automatic liquid handling for life science: a critical review of the current
      state of the art.
AB  - Liquid handling plays a pivotal role in life science laboratories. In experiments
      such as gene sequencing, protein crystallization, antibody testing, and drug
      screening, liquid biosamples frequently must be transferred between containers of
      varying sizes and/or dispensed onto substrates of varying types. The sample
      volumes are usually small, at the micro- or nanoliter level, and the number of
      transferred samples can be huge when investigating large-scope combinatorial
      conditions. Under these conditions, liquid handling by hand is tedious, time
      consuming, and impractical. Consequently, there is a strong demand for automated
      liquid-handling methods such as sensor-integrated robotic systems. In this
      article, we survey the current state of the art in automatic liquid handling,
      including technologies developed by both industry and research institutions. We
      focus on methods for dealing with small volumes at high throughput and point out
      challenges for future advancements.

PMID- 22357569
TI  - Fall in peptic ulcer mortality associated with increased consultant input, prompt
      surgery and use of high dependency care identified through peer-review audit.
AB  - OBJECTIVES: Patients with peptic ulceration continue to present to surgeons with
      complications of bleeding or perforation and to die under surgical care. This
      study sought to examine whether improved consultant input, timely interventions
      and perioperative care could reduce mortality from peptic ulcer. DESIGN:
      Prospective collection of peer-review mortality data using Scottish Audit of
      Surgical Mortality methodologies (http://www.SASM.org) and analysed using SPSS.
      SETTING: Secondary care; all hospitals in Scotland, UK, admitting surgical
      patients over 13 years (1994-2006). PARTICIPANTS: 42 736 patients admitted (38
      782 operative and 3954 non-operative) with peptic ulcer disease; 1952 patients
      died (1338 operative and 614 non-operative deaths) with a diagnosis of peptic
      ulcer. PRIMARY AND SECONDARY OUTCOME MEASURES: Adverse events; consultant
      presence at operation, operations performed within 2 h and high
      dependency/intensive therapy unit (HDU/ITU) use. RESULTS: Annual mortality fell
      from 251 in 1994 to 83 in 2006, proportionately greater than the reduction in
      hospital admissions with peptic ulcer. Adverse events declined over time and were
      rare for non-operative patients. Consultant surgeon presence at operation rose
      from 40.0% in 1994 to 73.4% in 2006, operations performed within 2 h of admission
      from 10.3% in 1994 to 28.1% in 2006 and HDU/ITU use from 52.7% in 1994 to 84.4%
      in 2006. Consultant involvement (p=0.005) and HDU/ITU care (p=0.026) were
      significantly associated with a reduction in operative deaths. CONCLUSION:
      Patients with complications of peptic ulceration admitted under surgical care
      should be offered consultant surgeon input, timely surgery and HDU/ITU care.

PMID- 22357570
TI  - The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality
      control data from a cross-sectional investigation into the prevalence, severity,
      genetics, immunology and environmental factors affecting asthma in adolescence in
      Peru.
AB  - OBJECTIVES: According to a large-scale international survey, Peru has one of the
      highest prevalences of asthma worldwide; however, data from this survey were
      limited to participants from urban Lima. The authors sought to characterise the
      epidemiology of asthma in Peru in two regions with disparate degrees of
      urbanisation. In this manuscript, the authors summarise the study design and
      implementation. DESIGN: A cross-sectional study. PARTICIPANTS: Using census data
      of 13-15-year-old adolescents from two communities in Peru, the authors invited a
      random sample of participants in Lima (n=725) and all adolescents in Tumbes
      (n=716) to participate in our study. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      authors asked participants to complete a questionnaire on asthma symptoms,
      environmental exposures and socio-demographics and to undergo spirometry before
      and after bronchodilator, skin allergy testing and exhaled nitric oxide testing.
      The authors obtained blood samples for haematocrit, total IgE levels, vitamin D
      levels and DNA in all participants and measured indoor particulate matter
      concentrations for 48 h in a random subset of 70-100 households at each site.
      RESULTS: Of 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of
      enrolled) completed all physical tests. 1283 (89%) performed spirometry according
      to standard guidelines, of which 86% of prebronchodilator tests and 92% of
      postbronchodilator tests were acceptable and reproducible. 92% of allergy skin
      tests had an adequate negative control. The authors collected blood from 1146
      participants (79%) and saliva samples from 148 participants (9%). Overall amounts
      of DNA obtained from blood or saliva were 25.8 MUg, with a 260/280 ratio of 1.86.
      CONCLUSIONS: This study will contribute to the characterisation of a variety of
      risk factors for asthma, including urbanisation, total IgE levels, vitamin D
      levels and candidate genes, in a resource-poor setting. The authors present data
      to support high quality of survey, allergic, spirometric and genetic data
      collected in our study.

PMID- 22357571
TI  - What proportion of patients report long-term pain after total hip or knee
      replacement for osteoarthritis? A systematic review of prospective studies in
      unselected patients.
AB  - BACKGROUND: Total hip or knee replacement is highly successful when judged by
      prosthesis-related outcomes. However, some people experience long-term pain.
      OBJECTIVES: To review published studies in representative populations with total
      hip or knee replacement for the treatment of osteoarthritis reporting proportions
      of people by pain intensity. DATA SOURCES: MEDLINE and EMBASE databases searched
      to January 2011 with no language restrictions. Citations of key articles in ISI
      Web of Science and reference lists were checked. STUDY ELIGIBILITY CRITERIA,
      PARTICIPANTS AND INTERVENTIONS: Prospective studies of consecutive, unselected
      osteoarthritis patients representative of the primary total hip or knee
      replacement population, with intensities of patient-centred pain measured after 3
      months to 5-year follow-up. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors
      screened titles and abstracts. Data extracted by one author were checked
      independently against original articles by a second. For each study, the authors
      summarised the proportions of people with different severities of pain in the
      operated joint. RESULTS: Searches identified 1308 articles of which 115 reported
      patient-centred pain outcomes. Fourteen articles describing 17 cohorts (6 with
      hip and 11 with knee replacement) presented appropriate data on pain intensity.
      The proportion of people with an unfavourable long-term pain outcome in studies
      ranged from about 7% to 23% after hip and 10% to 34% after knee replacement. In
      the best quality studies, an unfavourable pain outcome was reported in 9% or more
      of patients after hip and about 20% of patients after knee replacement.
      LIMITATIONS: Other studies reported mean values of pain outcomes. These and
      routine clinical studies are potential sources of relevant data. CONCLUSIONS AND
      IMPLICATIONS OF KEY FINDINGS: After hip and knee replacement, a significant
      proportion of people have painful joints. There is an urgent need to improve
      general awareness of this possibility and to address determinants of good and bad
      outcomes.

PMID- 22357573
TI  - Criminality in men with Klinefelter's syndrome and XYY syndrome: a cohort study.
AB  - OBJECTIVE: To investigate the criminal pattern in men between 15 and 70 years of
      age diagnosed with 47,XXY (Klinefelter's syndrome (KS)) or 47,XYY compared to the
      general population. DESIGN: Register-based cohort study comparing the incidence
      of convictions among men with KS and with 47,XYY with age- and calendar-matched
      samples of the general population. Crime was classified into eight types (sexual
      abuse, homicide, burglary, violence, traffic, drug-related, arson and 'others').
      SETTING: Denmark 1978-2006. PARTICIPANTS: All men diagnosed with KS (N=934) or
      47,XYY (N=161) at risk and their age- and calendar-time-matched controls (N=88
      979 and 15 356, respectively). RESULTS: The incidence of convictions was
      increased in men with KS (omitting traffic offenses) compared to controls with a
      HR of 1.40 (95% CI 1.23 to 1.59, p<0.001), with significant increases in sexual
      abuse, burglary, arson and 'others', but with a decreased risk of traffic and
      drug-related offenses. The incidence of convictions was significantly increased
      among men with 47,XYY compared to controls with a HR of 1.42 (95% CI 1.14 to
      1.77, p<0.005) in all crime types, except drug-related crimes and traffic.
      Adjusting for socioeconomic variables (education, fatherhood, retirement and
      cohabitation) reduced the total HR for both KS and 47,XYY to levels similar to
      controls, while some specific crime types (sexual abuse, arson, etc) remained
      increased. CONCLUSION: The overall risk of conviction (excluding traffic
      offenses) was moderately increased in men with 47,XYY or KS; however, it was
      similar to controls when adjusting for socioeconomic parameters. Convictions for
      sexual abuse, burglary, arson and 'others' were significantly increased. The
      increased risk of convictions may be partly or fully explained by the poor
      socioeconomic conditions related to the chromosome aberrations.

PMID- 22357572
TI  - Minocycline and aspirin in the treatment of bipolar depression: a protocol for a
      proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical
      trial.
AB  - INTRODUCTION: New medication classes are needed to improve treatment
      effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence
      suggests that BD is characterised by neural changes such as dendritic remodelling
      and glial and neuronal cell loss. These changes have been hypothesised to result
      from chronic inflammation. The principal aims of the proposed research is to
      evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug
      with neuroprotective and immune-modulating properties, and of aspirin, at doses
      expected to selectively inhibit cyclooxygenase 1 (COX-1). METHODS AND ANALYSIS:
      120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for
      BD (type I or II) and for a current major depressive episode will be recruited to
      take part in a randomised, double-blind, placebo-controlled, parallel-group,
      proof-of-concept clinical trial following a 2*2 design. As adjuncts to existing
      treatment, subjects will be randomised to receive one of the four treatment
      combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus
      placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline
      plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily
      and 81 mg twice daily, respectively. Antidepressant response will be evaluated by
      assessing changes in the Montgomery-Asberg Depression Rating Scale scores between
      baseline and the end of the 6-week trial. As secondary outcome measures, the anti
      inflammatory effects of minocycline and aspirin will be tested by measuring pre
      treatment and post-treatment levels of C reactive protein and inflammatory
      cytokines. ETHICS AND DISSEMINATION: Minocycline has been widely used as an
      antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a
      worldwide scale for its role as an antithrombotic and thrombolytic. The study
      progress will be overseen by a Data, Safety and Monitoring Board, which will meet
      once every 6 months. Results of the study will be published in peer-reviewed
      publications. TRIAL REGISTRATION NUMBER: Clinical Trials.gov: NCT01429272.

PMID- 22357574
TI  - Atrial resynchronization therapy: a new concept for treatment of heart failure
      with preserved ejection fraction and prevention of atrial fibrillation?

PMID- 22357575
TI  - Stroke aetiology in heart failure: towards patient-tailored prevention of stroke.

PMID- 22357577
TI  - Clinical course and predictive value of liver function tests in patients
      hospitalized for worsening heart failure with reduced ejection fraction: an
      analysis of the EVEREST trial.
AB  - AIMS: Abnormal liver function tests (LFTs) are common in ambulatory heart failure
      (HF). The aim of this study was to characterize abnormal LFTs during index
      hospitalization. METHODS AND RESULTS: A post-hoc analysis was carried out of the
      placebo group of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure
      Outcome Study with Tolvaptan) trial, which enrolled patients hospitalized for HF
      with an ejection fraction (EF) <=40% and no history of primary significant liver
      disease or acute hepatic failure. LFTs (abbreviation, cut-offs for abnormal
      values) including serum albumin (ALB, <3.3 g/dL), aspartate transaminase (AST,
      >34 IU/L), alanine transaminase (ALT, >34 IU/L), alkaline phosphatase (AP, >123
      IU/L),gamma-glutamyl transferase (GGT, >50 IU/L), and total bilirubin (T Bili,
      >1.2 mg/dL) were measured at baseline, discharge/day 7, and post-discharge. Co
      primary endpoints were all-cause mortality (ACM) and cardiovascular mortality or
      first HF hospitalization (CVM + HFH). Study participants had a mean age of 65.6
      +/-12.0 years, were mostly male, reported high prevalences of medical co
      morbidities, and were well treated with evidence-based therapies. Baseline LFT
      abnormalities were common (ALB 17%, AST 21%, ALT 21%, AP 23%, GGT 62%, and T Bili
      26%). Abnormal T Bili was the only marker to decrease substantially from baseline
      (26%) to discharge/day 7 (19%). All LFTs, except AP, improved post-discharge.
      Lower baseline ALB and elevated T Bili were associated with higher rates of ACM,
      and in-hospital decreases in ALB and increases in T Bili were associated with
      higher rates of both ACM and CVM + HFH. CONCLUSION: LFT abnormalities are common
      during hospitalization for HF in patients with reduced EF and were persistent at
      discharge. Baseline and in-hospital changes in ALB and T Bili provide additional
      prognostic value.

PMID- 22357576
TI  - Right ventricular dysfunction is associated with chronic kidney disease and
      predicts survival in patients with chronic systolic heart failure.
AB  - AIMS: Chronic kidney disease (CKD) and right ventricular (RV) dysfunction are
      important predictors of prognosis in heart failure (HF). We investigated the
      relationship between RV dysfunction and CKD in outpatients with chronic systolic
      HF, an association which remains poorly defined. METHODS AND RESULTS: Outpatients
      (n = 373) with chronic HF and left ventricular ejection fraction (LVEF) <=45%
      underwent clinical and echo-Doppler evaluations and were followed up for 31 +/-
      24 months. Tricuspid annular plane systolic excursion (TAPSE) assessed RV
      dysfunction. The estimated glomerular filtration rate (GFR) was measured by the
      simplified Modification of Diet in Renal Disease (MDRD) formula. Correlation
      analysis was used to characterize the association between TAPSE and estimated
      GFR. Odds ratios (ORs) for CKD and hazard ratios (HRs) for all-cause mortality
      were assessed using multivariable logistic or proportional hazards regression
      models. TAPSE and estimated GFR were significantly correlated (r = 0.38, P <
      0.0001). TAPSE <=14 mm was associated with elevated estimated right atrial
      pressure and N-terminal pro brain natriuretic peptide levels. TAPSE <=14 mm
      increased the odds of estimated GFR <60 mL/min/1.73 m(2), OR [95% confidence
      interval (CI)] = 2.51(1.44-4.39), P < 0.0001 and predicted all-cause mortality,
      HR (95% CI) = 1.80 (1.20-2.71) after multivariable adjustment. CONCLUSIONS: Right
      ventricular dysfunction is cross-sectionally associated with CKD and
      prospectively predicts survival in outpatients with chronic systolic HF. These
      data suggest RV dysfunction to be one of the possible mechanistic links between
      HF and CKD.

PMID- 22357578
TI  - Demographics and diagnoses at rural health camps in Nepal: cross-sectional study.
AB  - BACKGROUND: The charity 'Health Partnership Nepal' is committed to both improving
      global health care and providing medical training links between Nepal and the UK.
      This paper analyses data gathered at rural health camps. AIM: To describe the
      demographics, diagnoses and treatments offered to people attending three rural
      health camps in Nepal during 2009. Design Cross-sectional study. Setting Three
      free health care camps established within the Nuwakot district of Nepal during
      April-May 2009. Camps were staffed by doctors including GPs, nurses and medical
      students from London and Kathmandu. METHODS: Attendees had treatment sheets
      completed which recorded their demographics, diagnoses and dispensed medications.
      RESULTS: The mean age of the 1903 consecutive patients attending was 42.8 years
      (range one month to 98 years) of whom 68.6% were female and 13.7% were children.
      The majority, 82.3%, were agricultural workers. For adults (n = 1574), the most
      frequent complaints were stomach pain 20.1%, musculoskeletal pain 19.3% and
      visual acuity problems 6.1%. Stomach pain was significantly more common in women
      than men [21.2% (236/1064) versus 14.5% (65/449) P < 0.01]. For children (n =
      249), the most common diagnoses were helminthiasis 10.4%, conjunctivitis 7.6% and
      upper respiratory tract infection 7.2%. Overall, opthalmological,
      gastroenterological and rheumatological diagnoses were significantly more common
      in Nepalese than UK general practice patients. Of 1109 recorded prescriptions,
      the most common were multivitamins 23%, oral analgesics 15% and oral antibiotics
      14%. CONCLUSIONS: There is a considerable unmet disease burden within rural
      districts of Nepal particularly for stomach pain, musculoskeletal pain and visual
      acuity problems. When planning similar rurally based health camps, we recommend
      recruiting GPs and ophthalmologists.

PMID- 22357579
TI  - Heroin users' experiences of depression: a qualitative study.
AB  - BACKGROUND: Heroin users represent a challenging group of patients for GPs, with
      a high morbidity including a high prevalence of depression. Compared to other
      groups, management of 'depression' in heroin users is likely to require different
      approaches.  Aim. To examine heroin users' beliefs about connections between
      depressive symptoms and drug taking. DESIGN: Qualitative. SETTING: Primary care.
      METHODS: A total of 17 semi-structured interviews were conducted with patients
      receiving opioid substitution therapy and antidepressants. One focus group of
      service users was also interviewed. RESULTS: A wide range of thoughts and
      emotions were described as 'depression'. Adverse childhood events were viewed as
      both the cause of depression and as simultaneously placing the individual in
      social circles where drug use was common. Drug taking was thought to lead to
      depression through resultant adverse social consequences, though illicit drug use
      was also regarded as an understandable way to cope with depression. Examples of
      stigma from taking drugs were commonly described and thought a cause of
      depression; in contrast, stigmatizing effects of depression were not apparent.
      The participants often felt isolated. Beliefs about how antidepressants worked
      incorporated ideas about blocking out thoughts, stopping thoughts racing and
      keeping emotions level. Self-management techniques for treating depression were
      rarely described. CONCLUSIONS: Heroin users' experiences of depression-including
      ideas about causation, how symptoms are felt and experienced and treatment
      strategies-are overwhelmingly framed by the context of drug taking.

PMID- 22357580
TI  - Biophysics, bioenergetics and mechanistic approaches to ecology.

PMID- 22357581
TI  - Changing environments and structure--property relationships in marine
      biomaterials.
AB  - Most marine organisms make functional biomolecular materials that extend to
      varying degrees 'beyond their skins'. These materials are very diverse and
      include shells, spines, frustules, tubes, mucus trails, egg capsules and byssal
      threads, to mention a few. Because they are devoid of cells, these materials lack
      the dynamic maintenance afforded intra-organismic tissues and thus are usually
      assumed to be inherently more durable than their internalized counterparts.
      Recent advances in nanomechanics and submicron spectroscopic imaging have enabled
      the characterization of structure-property relationships in a variety of extra
      organismic materials and provided important new insights about their adaptive
      functions and stability. Some structure-property relationships in byssal threads
      are described to show how available analytical methods can reveal hitherto
      unappreciated interdependences between these materials and their prevailing
      chemical, physical and ecological environments.

PMID- 22357582
TI  - Comparative genomics in ecological physiology: toward a more nuanced
      understanding of acclimation and adaptation.
AB  - Organisms that live in variable environments must adjust their physiology to
      compensate for environmental change. Modern functional genomics technologies
      offer global top-down discovery-based tools for identifying and exploring the
      mechanistic basis by which organisms respond physiologically to a detected change
      in the environment. Given that populations and species from different niches may
      exhibit different acclimation abilities, comparative genomic approaches may offer
      more nuanced understanding of acclimation responses, and provide insight into the
      mechanistic and genomic basis of variable acclimation. The physiological genomics
      literature is large and growing, as is the comparative evolutionary genomics
      literature. Yet, expansion of physiological genomics experiments to exploit
      taxonomic variation remains relatively undeveloped. Here, recent advances in the
      emerging field of comparative physiological genomics are considered, including
      examples of plants, bees and fish, and opportunities for further development are
      outlined particularly in the context of climate change research. Elements of
      robust experimental design are discussed with emphasis on the phylogenetic
      comparative approach. Understanding how acclimation ability is partitioned among
      populations and species in nature, and knowledge of the relevant genes and
      mechanisms, will be important for characterizing and predicting the ecological
      and evolutionary consequences of human-accelerated environmental change.

PMID- 22357583
TI  - Integrating dynamic energy budget (DEB) theory with traditional bioenergetic
      models.
AB  - Dynamic energy budget (DEB) theory offers a systematic, though abstract, way to
      describe how an organism acquires and uses energy and essential elements for
      physiological processes, in addition to how physiological performance is
      influenced by environmental variables such as food density and temperature. A
      'standard' DEB model describes the performance (growth, development,
      reproduction, respiration, etc.) of all life stages of an animal (embryo to
      adult), and predicts both intraspecific and interspecific variation in
      physiological rates. This approach contrasts with a long tradition of more
      phenomenological and parameter-rich bioenergetic models that are used to make
      predictions from species-specific rate measurements. These less abstract models
      are widely used in fisheries studies; they are more readily interpretable than
      DEB models, but lack the generality of DEB models. We review the interconnections
      between the two approaches and present formulae relating the state variables and
      fluxes in the standard DEB model to measured bioenergetic rate processes. We
      illustrate this synthesis for two large fishes: Pacific bluefin tuna (Thunnus
      orientalis) and Pacific salmon (Oncorhynchus spp.). For each, we have a parameter
      sparse, full-life-cycle DEB model that requires adding only a few species
      specific features to the standard model. Both models allow powerful integration
      of knowledge derived from data restricted to certain life stages, processes and
      environments.

PMID- 22357584
TI  - Linking biomechanics and ecology through predator-prey interactions: flight
      performance of dragonflies and their prey.
AB  - Aerial predation is a highly complex, three-dimensional flight behavior that
      affects the individual fitness and population dynamics of both predator and prey.
      Most studies of predation adopt either an ecological approach in which capture or
      survival rates are quantified, or a biomechanical approach in which the physical
      interaction is studied in detail. In the present study, we show that combining
      these two approaches provides insight into the interaction between hunting
      dragonflies (Libellula cyanea) and their prey (Drosophila melanogaster) that
      neither type of study can provide on its own. We performed >2500 predation trials
      on nine dragonflies housed in an outdoor artificial habitat to identify sources
      of variability in capture success, and analyzed simultaneous predator-prey flight
      kinematics from 50 high-speed videos. The ecological approach revealed that
      capture success is affected by light intensity in some individuals but that prey
      density explains most of the variability in success rate. The biomechanical
      approach revealed that fruit flies rarely respond to approaching dragonflies with
      evasive maneuvers, and are rarely successful when they do. However, flies perform
      random turns during flight, whose characteristics differ between individuals, and
      these routine, erratic turns are responsible for more failed predation attempts
      than evasive maneuvers. By combining the two approaches, we were able to
      determine that the flies pursued by dragonflies when prey density is low fly more
      erratically, and that dragonflies are less successful at capturing them. This
      highlights the importance of considering the behavior of both participants, as
      well as their biomechanics and ecology, in developing a more integrative
      understanding of organismal interactions.

PMID- 22357585
TI  - Methodological advances in predicting flow-induced dynamics of plants using
      mechanical-engineering theory.
AB  - The modeling of fluid-structure interactions, such as flow-induced vibrations, is
      a well-developed field of mechanical engineering. Many methods exist, and it
      seems natural to apply them to model the behavior of plants, and potentially
      other cantilever-like biological structures, under flow. Overcoming this
      disciplinary divide, and the application of such models to biological systems,
      will significantly advance our understanding of ecological patterns and processes
      and improve our predictive capabilities. Nonetheless, several methodological
      issues must first be addressed, which I describe here using two practical
      examples that have strong similarities: one from agricultural sciences and the
      other from nuclear engineering. Very similar issues arise in both: individual and
      collective behavior, small and large space and time scales, porous modeling,
      standard and extreme events, trade-off between the surface of exchange and
      individual or collective risk of damage, variability, hostile environments and,
      in some aspects, evolution. The conclusion is that, although similar issues do
      exist, which need to be exploited in some detail, there is a significant gap that
      requires new developments. It is obvious that living plants grow in and adapt to
      their environment, which certainly makes plant biomechanics fundamentally
      distinct from classical mechanical engineering. Moreover, the selection processes
      in biology and in human engineering are truly different, making the issue of
      safety different as well. A thorough understanding of these similarities and
      differences is needed to work efficiently in the application of a mechanistic
      approach to ecology.

PMID- 22357586
TI  - Biomechanics meets the ecological niche: the importance of temporal data
      resolution.
AB  - The emerging field of mechanistic niche modelling aims to link the functional
      traits of organisms to their environments to predict survival, reproduction,
      distribution and abundance. This approach has great potential to increase our
      understanding of the impacts of environmental change on individuals, populations
      and communities by providing functional connections between physiological and
      ecological response to increasingly available spatial environmental data. By
      their nature, such mechanistic models are more data intensive in comparison with
      the more widely applied correlative approaches but can potentially provide more
      spatially and temporally explicit predictions, which are often needed by decision
      makers. A poorly explored issue in this context is the appropriate level of
      temporal resolution of input data required for these models, and specifically the
      error in predictions that can be incurred through the use of temporally averaged
      data. Here, we review how biomechanical principles from heat-transfer and
      metabolic theory are currently being used as foundations for mechanistic niche
      models and consider the consequences of different temporal resolutions of
      environmental data for modelling the niche of a behaviourally thermoregulating
      terrestrial lizard. We show that fine-scale temporal resolution (daily) data can
      be crucial for unbiased inference of climatic impacts on survival, growth and
      reproduction. This is especially so for species with little capacity for
      behavioural buffering, because of behavioural or habitat constraints, and for
      detecting temporal trends. However, coarser-resolution data (long-term monthly
      averages) can be appropriate for mechanistic studies of climatic constraints on
      distribution and abundance limits in thermoregulating species at broad spatial
      scales.

PMID- 22357587
TI  - Biophysics, environmental stochasticity, and the evolution of thermal safety
      margins in intertidal limpets.
AB  - As the air temperature of the Earth rises, ecological relationships within a
      community might shift, in part due to differences in the thermal physiology of
      species. Prediction of these shifts - an urgent task for ecologists - will be
      complicated if thermal tolerance itself can rapidly evolve. Here, we employ a
      mechanistic approach to predict the potential for rapid evolution of thermal
      tolerance in the intertidal limpet Lottia gigantea. Using biophysical principles
      to predict body temperature as a function of the state of the environment, and an
      environmental bootstrap procedure to predict how the environment fluctuates
      through time, we create hypothetical time-series of limpet body temperatures,
      which are in turn used as a test platform for a mechanistic evolutionary model of
      thermal tolerance. Our simulations suggest that environmentally driven stochastic
      variation of L. gigantea body temperature results in rapid evolution of a
      substantial 'safety margin': the average lethal limit is 5-7 degrees C above the
      average annual maximum temperature. This predicted safety margin approximately
      matches that found in nature, and once established is sufficient, in our
      simulations, to allow some limpet populations to survive a drastic, century-long
      increase in air temperature. By contrast, in the absence of environmental
      stochasticity, the safety margin is dramatically reduced. We suggest that the
      risk of exceeding the safety margin, rather than the absolute value of the safety
      margin, plays an underappreciated role in the evolution of thermal tolerance. Our
      predictions are based on a simple, hypothetical, allelic model that connects
      genetics to thermal physiology. To move beyond this simple model - and thereby
      potentially to predict differential evolution among populations and among species
      - will require significant advances in our ability to translate the details of
      thermal histories into physiological and population-genetic consequences.

PMID- 22357588
TI  - Integrating mechanistic organism--environment interactions into the basic theory
      of community and evolutionary ecology.
AB  - This paper presents an overview of how mechanistic knowledge of organism
      environment interactions, including biomechanical interactions of heat, mass and
      momentum transfer, can be integrated into basic theoretical population biology
      through mechanistic functional responses that quantitatively describe how
      organisms respond to their physical environment. Integrating such functional
      responses into simple community and microevolutionary models allows scaling up of
      the organism-level understanding from biomechanics both ecologically and
      temporally. For community models, Holling-type functional responses for predator
      prey interactions provide a classic example of the functional response affecting
      qualitative model dynamics, and recent efforts are expanding analogous models to
      incorporate environmental influences such as temperature. For evolutionary
      models, mechanistic functional responses dependent on the environment can serve
      as fitness functions in both quantitative genetic and game theoretic frameworks,
      especially those concerning function-valued traits. I present a novel comparison
      of a mechanistic fitness function based on thermal performance curves to a
      commonly used generic fitness function, which quantitatively differ in their
      predictions for response to environmental change. A variety of examples
      illustrate how mechanistic functional responses enhance model connections to
      biologically relevant traits and processes as well as environmental conditions
      and therefore have the potential to link theoretical and empirical studies.
      Sensitivity analysis of such models can provide biologically relevant insight
      into which parameters and processes are important to community and evolutionary
      responses to environmental change such as climate change, which can inform
      conservation management aimed at protecting response capacity. Overall, the
      distillation of detailed knowledge or organism-environment interactions into
      mechanistic functional responses in simple population biology models provides a
      framework for integrating biomechanics and ecology that allows both tractability
      and generality.

PMID- 22357589
TI  - The influence of local- and landscape-scale processes on spatial self
      organization in estuarine ecosystems.
AB  - Complexity theory proposes that spatial self-organization, the process whereby
      small-scale, localized interactions among the components of a system generate
      complex spatial structures at large spatial scales, explains the formation of
      autogenic spatial patterns in ecosystems. We question this premise by reviewing
      three estuarine ecosystems - mussel beds, mudflats and salt marshes - where self
      organization has been put forward to explain spatial patterns. Our review
      highlights that these self-organized estuarine systems are shaped by the
      combination of small-scale interactions between ecological and physical processes
      on the one hand, and large-scale physical forcing on the other. More
      specifically, local interactions generate patchiness at small spatial scales,
      whereas landscape forcing determines the shape and orientation of these patches
      in the landscape. We present a framework that illustrates how self-organized
      ecosystems are shaped by interactions between organisms and physical processes
      occurring at multiple spatial scales. Moreover, the present review of estuarine
      systems underlines that scale-dependent feedbacks are capable of explaining
      spatial patterns that are much more complex than the regular patterns to which
      they have been applied so far.

PMID- 22357590
TI  - Integrating physiological and biomechanical drivers of population growth over
      environmental gradients on coral reefs.
AB  - Coral reefs exhibit marked spatial and temporal variability, and coral reef
      organisms exhibit trade-offs in functional traits that influence demographic
      performance under different combinations of abiotic environmental conditions. In
      many systems, trait trade-offs are modelled using an energy and/or nutrient
      allocation framework. However, on coral reefs, differences in biomechanical
      vulnerability have major demographic implications, and indeed are believed to
      play an essential role in mediating species coexistence because highly
      competitive growth forms are vulnerable to physical dislodgment events that occur
      with high frequency (e.g. annual summer storms). Therefore, an integrated energy
      allocation and biomechanics framework is required to understand the effect of
      physical environmental gradients on species' demographic performance. However, on
      coral reefs, as in most ecosystems, the effects of environmental conditions on
      organisms are measured in different currencies (e.g. lipid accumulation, survival
      and number of gametes), and thus the relative contributions of these effects to
      overall capacity for population growth are not readily apparent. A comprehensive
      assessment of links between the environment and the organism, including those
      mediated by biomechanical processes, must convert environmental effects on
      individual-level performance (e.g. survival, growth and reproduction) into a
      common currency that is relevant to the capacity to contribute to population
      growth. We outline such an approach by considering the population-level
      performance of scleractinian reef corals over a hydrodynamic gradient, with a
      focus on the integrating the biomechanical determinants of size-dependent coral
      colony dislodgment as a function of flow, with the effects of flow on
      photosynthetic energy acquisition and respiration.

PMID- 22357591
TI  - Linking patterns and processes across scales: the application of scale-transition
      theory to algal dynamics on rocky shores.
AB  - Understanding how species and environments respond to global anthropogenic
      disturbances is one of the greatest challenges for contemporary ecology. The
      ability to integrate modeling, correlative and experimental approaches within
      individual research programs will be key to address large-scale, long-term
      environmental problems. Scale-transition theory (STT) enables this level of
      integration, providing a powerful framework to link ecological patterns and
      processes across spatial and temporal scales. STT predicts the large-scale (e.g.
      regional) behavior of a system on the basis of nonlinear population models
      describing local (e.g. patch-scale) dynamics and the interaction between these
      nonlinearities and spatial variation in population abundance or environmental
      conditions. Here we use STT to predict the dynamics of turf-forming algae on
      rocky shores at Capraia Island, in the northwest Mediterranean. We developed a
      model of algal turf dynamics based on density-dependent growth that included the
      effects of local interactions with canopy algae. The model was parameterized with
      field data and used to scale up the dynamics of algal turfs from the plot scale
      (20*20 cm) to the island scale (tens of km). The interaction between nonlinear
      growth and spatial variance in cover of turfing algae emerged as a key term to
      translate the local dynamics up to the island scale. The model successfully
      predicted short-term and long-term mean values of turf cover estimated
      independently from a separate experiment. These results illustrate how STT can be
      used to identify the relevant mechanisms that drive large-scale changes in
      ecological communities. We argue that STT can contribute significantly to the
      connection between biomechanics and ecology, a synthesis that is at the core of
      the emerging field of ecomechanics.

PMID- 22357592
TI  - Using tri-axial acceleration data to identify behavioral modes of free-ranging
      animals: general concepts and tools illustrated for griffon vultures.
AB  - Integrating biomechanics, behavior and ecology requires a mechanistic
      understanding of the processes producing the movement of animals. This calls for
      contemporaneous biomechanical, behavioral and environmental data along movement
      pathways. A recently formulated unifying movement ecology paradigm facilitates
      the integration of existing biomechanics, optimality, cognitive and random
      paradigms for studying movement. We focus on the use of tri-axial acceleration
      (ACC) data to identify behavioral modes of GPS-tracked free-ranging wild animals
      and demonstrate its application to study the movements of griffon vultures (Gyps
      fulvus, Hablizl 1783). In particular, we explore a selection of nonlinear and
      decision tree methods that include support vector machines, classification and
      regression trees, random forest methods and artificial neural networks and
      compare them with linear discriminant analysis (LDA) as a baseline for
      classifying behavioral modes. Using a dataset of 1035 ground-truthed ACC
      segments, we found that all methods can accurately classify behavior (80-90%)
      and, as expected, all nonlinear methods outperformed LDA. We also illustrate how
      ACC-identified behavioral modes provide the means to examine how vulture flight
      is affected by environmental factors, hence facilitating the integration of
      behavioral, biomechanical and ecological data. Our analysis of just over three
      quarters of a million GPS and ACC measurements obtained from 43 free-ranging
      vultures across 9783 vulture-days suggests that their annual breeding schedule
      might be selected primarily in response to seasonal conditions favoring rising
      air columns (thermals) and that rare long-range forays of up to 1750 km from the
      home range are performed despite potentially heavy energetic costs and a low rate
      of food intake, presumably to explore new breeding, social and long-term resource
      location opportunities.

PMID- 22357593
TI  - Roles of transport and mixing processes in kelp forest ecology.
AB  - Fluid-dynamic transport and mixing processes affect birth, death, immigration and
      emigration rates in kelp forests, and can modulate broader community
      interactions. In the most highly studied canopy-forming kelp, Macrocystis
      pyrifera (the giant kelp), models of hydrodynamic and oceanographic phenomena
      influencing spore movement provide bounds on reproduction, quantify patterns of
      local and regional propagule supply, identify scales of population connectivity,
      and establish context for agents of early life mortality. Other analyses yield
      insight into flow-mediated species interactions within kelp forests. In each
      case, advances emerge from the use of ecomechanical approaches that propagate
      physical-biological connections at the scale of the individual to higher levels
      of ecological organization. In systems where physical factors strongly influence
      population, community or ecosystem properties, such mechanics-based methods
      promote crucial progress but are just beginning to realize their full potential.

PMID- 22357594
TI  - Plankton distribution and ocean dispersal.
AB  - Plankton are small organisms that dwell in oceans, seas and bodies of fresh
      water. In this review, we discuss life in the plankton, which involves a balance
      between the behavioral capabilities of the organism and the characteristics and
      movement of the water that surrounds it. In order to consider this balance, we
      discuss how plankton interact with their environment across a range of scales -
      from the smallest viruses and bacteria to larger phytoplankton and zooplankton.
      We find that the larger scale distributions of plankton, observed in coastal
      waters, along continental shelves and in ocean basins, are highly dependent upon
      the smaller scale interactions between the individual organism and its
      environment. Further, we discuss how larger scale organism distributions may
      affect the transport and/or retention of plankton in the ocean environment. The
      research reviewed here provides a mechanistic understanding of how organism
      behavior in response to the physical environment produces planktonic
      aggregations, which has a direct impact on the way marine ecosystems function.

PMID- 22357595
TI  - Seascapes: the world of aquatic organisms as determined by their particulate
      natures.
AB  - The interactions between planktonic organisms and their aquatic environment are
      mediated by diffusive processes on the scale of millimeters and smaller. The
      uptake of nutrients and food and the release of metabolic products creates
      localized patchiness that diffusive processes homogenize. Organism size
      determines, to a large extent, the character of these interactions. This paper
      builds a framework for considering these interactions, starting with an analysis
      of the diffusive environment around individual organisms and concluding with an
      integration over a range of organism sizes to describe aggregated properties.
      Several examples show the importance of the size-based abundance of organisms and
      other particles in determining the duration, spatial extent and frequency of
      environmental cues. One implication of these results is that microbial
      chemotactic behavior does not help them to find and utilize the majority of
      nutrient releases.

PMID- 22357596
TI  - The role of structured stirring and mixing on gamete dispersal and aggregation in
      broadcast spawning.
AB  - Broadcast-spawning benthic invertebrates synchronously release sperm and eggs
      from separate locations into the surrounding flow, whereupon the process depends
      on structured stirring by the flow field (at large scales), and sperm motility
      and taxis (at small scales) to bring the gametes together. The details of the
      relevant physical and biological aspects of the problem that result in successful
      and efficient fertilization are not well understood. This review paper includes
      relevant work from both the physical and biological communities to synthesize a
      more complete understanding of the processes that govern fertilization success;
      the focus is on the role of structured stirring on the dispersal and aggregation
      of gametes. The review also includes a summary of current trends and approaches
      for numerical and experimental simulations of broadcast spawning.

PMID- 22357597
TI  - Biogenic inputs to ocean mixing.
AB  - Recent studies have evoked heated debate about whether biologically generated (or
      biogenic) fluid disturbances affect mixing in the ocean. Estimates of biogenic
      inputs have shown that their contribution to ocean mixing is of the same order as
      winds and tides. Although these estimates are intriguing, further study using
      theoretical, numerical and experimental techniques is required to obtain
      conclusive evidence of biogenic mixing in the ocean. Biogenic ocean mixing is a
      complex problem that requires detailed understanding of: (1) marine organism
      behavior and characteristics (i.e. swimming dynamics, abundance and migratory
      behavior), (2) mechanisms utilized by swimming animals that have the ability to
      mix stratified fluids (i.e. turbulence and fluid drift) and (3) knowledge of the
      physical environment to isolate contributions of marine organisms from other
      sources of mixing. In addition to summarizing prior work addressing the points
      above, observations on the effect of animal swimming mode and body morphology on
      biogenic fluid transport will also be presented. It is argued that to inform the
      debate on whether biogenic mixing can contribute to ocean mixing, our studies
      should focus on diel vertical migrators that traverse stratified waters of the
      upper pycnocline. Based on our understanding of mixing mechanisms, body
      morphologies, swimming modes and body orientation, combined with our knowledge of
      vertically migrating populations of animals, it is likely that copepods, krill
      and some species of gelatinous zooplankton and fish have the potential to be
      strong sources of biogenic mixing.

PMID- 22357598
TI  - The infinitely many genes model for the distributed genome of bacteria.
AB  - The distributed genome hypothesis states that the gene pool of a bacterial taxon
      is much more complex than that found in a single individual genome. However, the
      possible fitness advantage, why such genomic diversity is maintained, whether
      this variation is largely adaptive or neutral, and why these distinct individuals
      can coexist, remains poorly understood. Here, we present the infinitely many
      genes (IMG) model, which is a quantitative, evolutionary model for the
      distributed genome. It is based on a genealogy of individual genomes and the
      possibility of gene gain (from an unbounded reservoir of novel genes, e.g., by
      horizontal gene transfer from distant taxa) and gene loss, for example, by
      pseudogenization and deletion of genes, during reproduction. By implementing
      these mechanisms, the IMG model differs from existing concepts for the
      distributed genome, which cannot differentiate between neutral evolution and
      adaptation as drivers of the observed genomic diversity. Using the IMG model, we
      tested whether the distributed genome of 22 full genomes of picocyanobacteria
      (Prochlorococcus and Synechococcus) shows signs of adaptation or neutrality. We
      calculated the effective population size of Prochlorococcus at 1.01 * 10(11) and
      predicted 18 distinct clades for this population, only six of which have been
      isolated and cultured thus far. We predicted that the Prochlorococcus pangenome
      contains 57,792 genes and found that the evolution of the distributed genome of
      Prochlorococcus was possibly neutral, whereas that of Synechococcus and the
      combined sample shows a clear deviation from neutrality.

PMID- 22357599
TI  - Relationship between asparagine metabolism and protein concentration in soybean
      seed.
AB  - The relationship between asparagine metabolism and protein concentration was
      investigated in soybean seed. Phenotyping of a population of recombinant inbred
      lines adapted to Illinois confirmed a positive correlation between free
      asparagine levels in developing seeds and protein concentration at maturity.
      Analysis of a second population of recombinant inbred lines adapted to Ontario
      associated the elevated free asparagine trait with two of four quantitative trait
      loci determining population variation for protein concentration, including a
      major one on chromosome 20 (linkage group I) which has been reported in multiple
      populations. In the seed coat, levels of asparagine synthetase were high at 50 mg
      and progressively declined until 150 mg seed weight, suggesting that nitrogenous
      assimilates are pre-conditioned at early developmental stages to enable a high
      concentration of asparagine in the embryo. The levels of asparaginase B1 showed
      an opposite pattern, being low at 50 mg and progressively increased until 150 mg,
      coinciding with an active phase of storage reserve accumulation. In a pair of
      genetically related cultivars, ~2-fold higher levels of asparaginase B1 protein
      and activity in seed coat, were associated with high protein concentration,
      reflecting enhanced flux of nitrogen. Transcript expression analyses attributed
      this difference to a specific asparaginase gene, ASPGB1a. These results
      contribute to our understanding of the processes determining protein
      concentration in soybean seed.

PMID- 22357603
TI  - Modulating cell-cell communication with a high-throughput label-free cell assay.
AB  - A high-throughput label-free cell assay for modulating cell-cell communication is
      demonstrated with the Epic(r) system, a resonant waveguide grating sensor
      platform. Natural killer (NK) cells are known to be able to recognize abnormal
      cells (e.g., cancer cells and cells presenting intercellular adhesion molecule 1
      [ICAM1] through cell surface receptors) and kill them. In this study, the effect
      of effecter cells NK92MI on two kinds of target cells, cervical cancer cells
      (HeLa) and Chinese hamster ovarian cells overexpressing ICAM1 (CHO-ICAM1), was
      examined. Living target cells' response to NK92MI cells was monitored in real
      time and measured as wavelength shift in picometers. The authors showed that the
      detectability of target cell response is affected by multiple factors: the ratio
      of effecter cells to target cells (E/T), the interaction time of the two types of
      cells, and the target cell type. For example, with the effecter cells NK92MI and
      the same incubation time of 16 h, a minimal E/T ratio of 1 is required to detect
      HeLa cell response, whereas an E/T of 0.5 is sufficient to detect CHO-ICAM1 cell
      response. The authors confirmed that NK92MI cell-mediated target cell
      cytotoxicity results in negative optical signals and is associated with apoptosis
      mainly through caspase pathways. Distinct optical signals could be generated with
      the pretreatment of the target cells with various known pharmaceutical reagents,
      making the assay useful for discovering new chemicals that may affect cell-cell
      communications.

PMID- 22357600
TI  - The splicing regulator Rbfox2 is required for both cerebellar development and
      mature motor function.
AB  - The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing
      of many important neuronal transcripts and have been implicated in a variety of
      neurological disorders. However, their roles in brain development and function
      are not well understood, in part due to redundancy in their activities. Here we
      show that, unlike Rbfox1 deletion, the CNS-specific deletion of Rbfox2 disrupts
      cerebellar development. Genome-wide analysis of Rbfox2(-/-) brain RNA identifies
      numerous splicing changes altering proteins important both for brain development
      and mature neuronal function. To separate developmental defects from alterations
      in the physiology of mature cells, Rbfox1 and Rbfox2 were deleted from mature
      Purkinje cells, resulting in highly irregular firing. Notably, the Scn8a mRNA
      encoding the Na(v)1.6 sodium channel, a key mediator of Purkinje cell pacemaking,
      is improperly spliced in RbFox2 and Rbfox1 mutant brains, leading to highly
      reduced protein expression. Thus, Rbfox2 protein controls a post-transcriptional
      program required for proper brain development. Rbfox2 is subsequently required
      with Rbfox1 to maintain mature neuronal physiology, specifically Purkinje cell
      pacemaking, through their shared control of sodium channel transcript splicing.

PMID- 22357604
TI  - Implementing a laboratory automation system: experience of a large clinical
      laboratory.
AB  - Laboratories today face increasing pressure to automate their operations as they
      are challenged by a continuing increase in workload, need to reduce expenditure,
      and difficulties in recruitment of experienced technical staff. Was the
      implementation of a laboratory automation system (LAS) in the Clinical
      Biochemistry Laboratory at Singapore General Hospital successful? There is no
      simple answer, so the following topics comparing and contrasting pre- and post
      LAS have been explored: turnaround time (TAT), laboratory errors, and staff
      satisfaction. The benefits and limitations of LAS from the laboratory experience
      were also reviewed. The mean TAT for both stat and routine samples decreased post
      LAS (30% and 13.4%, respectively). In the 90th percentile TAT chart, a 29%
      reduction was seen in the processing of stat samples on the LAS. However, no
      significant difference in the 90th percentile TAT was observed with routine
      samples. It was surprising to note that laboratory errors increased post-LAS.
      Considerable effort was needed to overcome the initial difficulties associated
      with adjusting to a new system, new software, and new working procedures.
      Although some of the known advantages and limitations of LAS have been validated,
      the claimed benefits such as improvements in TAT, laboratory errors, and staff
      morale were not evident in the initial months.

PMID- 22357605
TI  - Optimization of the separation of NDA-derivatized methylarginines by capillary
      and microchip electrophoresis.
AB  - The methylated arginines (MAs) monomethylarginine (MMA), asymmetric
      dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) have been shown to
      be independent predictors of cardiovascular disease. This article describes
      progress regarding the development of an analytical method capable of rapidly
      analyzing MAs using capillary electrophoresis (CE) and microchip electrophoresis
      (MCE) with laser-induced fluorescence (LIF) detection. Several parameters
      including buffer composition and separation voltage were optimized to achieve an
      ideal separation. The analytes of interest were derivatized with naphthalene-2,3
      dicarboxaldehyde (NDA) to produce fluorescent 1-cyanobenz[f]isoindole (CBI)
      derivatives and then subjected to CE analysis. Baseline resolution of SDMA, ADMA,
      MMA, and arginine was achieved in less than 8 min. The limits of detection for
      SDMA, ADMA, MMA, and arginine were determined to be 15, 20, 25, and 5 nM,
      respectively, which are well below the expected plasma concentrations. The CE
      separation method was then transferred to a glass MCE device with LIF detection.
      MAs were baseline resolved in 3 min on-chip using a 14 cm separation channel with
      detection limits of approximately 10 nM for each species. To the best of the
      authors' knowledge, this is the first report of the separation of MAs by MCE.

PMID- 22357606
TI  - A mechanical biomarker of cell state in medicine.
AB  - The mechanical properties of cells have been shown to be useful markers of cell
      state by the biophysics community. Here, I highlight clinical and research
      problems that this label-free, potentially inexpensive cellular biomarker can
      address and discuss technical challenges to realize automated instruments to
      achieve robust and high-throughput mechanical measurements. Important features
      found in traditional fluorescence-based flow cytometry that can enable cytometry
      based on mechanical properties (i.e., deformability cytometry) are emphasized,
      especially the need for throughput, simple operation, multidimensional data
      visualization, and internal controls. Next-generation approaches to automate
      deformability measurements of cells are surveyed, and future directions are
      outlined that promise to bring low-cost mechanical measurements to medicine and
      biological research.

PMID- 22357608
TI  - Reservoir-based polymer drug delivery systems.
AB  - The importance of drug delivery has increased over the past decades, and
      significant advances have been made in the development of novel technologies.
      This review focuses on the use of different polymer drug delivery systems and
      their advancement toward clinical applications.

PMID- 22357607
TI  - Lens-free imaging for biological applications.
AB  - Lens-free (or lensless) imaging is emerging as a cost-effective, compact, and
      lightweight detection method that can serve numerous biological applications.
      Lens-free imaging can generate high-resolution images within a field-portable
      platform, which is ideal for affordable point-of-care devices aiming at resource
      limited settings. In this mini-review, we first describe different modes of
      operation for lens-free imaging and then highlight several recent biological
      applications of this emerging platform technology.

PMID- 22357609
TI  - Advances in wound-healing assays for probing collective cell migration.
AB  - Collective cell migration plays essential roles in a wide spectrum of biological
      processes, such as embryogenesis, tissue regeneration, and cancer metastasis.
      Numerous wound-healing assays based on mechanical, chemical, optical, and
      electrical approaches have been developed to create model "wounds" in cell
      monolayers to study the collective cell migration processes. These approaches can
      result in different microenvironments for cells to migrate and possess diverse
      assay characteristics in terms of simplicity, throughput, reproducibility, and
      multiplexability. In this review, we provide an overview of advances in wound
      healing assays and discuss their advantages and limitations in studying
      collective cell migration.

PMID- 22357610
TI  - Automated zebrafish chorion removal and single embryo placement: optimizing
      throughput of zebrafish developmental toxicity screens.
AB  - The potential of the developing zebrafish model for toxicology and drug discovery
      is limited by inefficient approaches to manipulating and chemically exposing
      zebrafish embryos-namely, manual placement of embryos into 96- or 384-well plates
      and exposure of embryos while still in the chorion, a barrier of poorly
      characterized permeability enclosing the developing embryo. We report the
      automated dechorionation of 1600 embryos at once at 4 h postfertilization (hpf)
      and placement of the dechorionated embryos into 96-well plates for exposure by 6
      hpf. The process removed >=95% of the embryos from their chorions with 2% embryo
      mortality by 24 hpf, and 2% of the embryos malformed at 120 hpf. The robotic
      embryo placement allocated 6-hpf embryos to 94.7% +/- 4.2% of the wells in
      multiple 96-well trials. The rate of embryo mortality was 2.8% (43 of 1536) from
      robotic handling, the rate of missed wells was 1.2% (18 of 1536), and the
      frequency of multipicks was <0.1%. Embryo malformations observed at 24 hpf
      occurred nearly twice as frequently from robotic handling (16 of 864; 1.9%) as
      from manual pipetting (9 of 864; 1%). There was no statistical difference between
      the success of performing the embryo placement robotically or manually.

PMID- 22357612
TI  - Global profiling of DNA methylation erasure in mouse primordial germ cells.
AB  - Epigenetic reprogramming, characterized by loss of cytosine methylation and
      histone modifications, occurs during mammalian development in primordial germ
      cells (PGCs), yet the targets and kinetics of this process are poorly
      characterized. Here we provide a map of cytosine methylation on a large portion
      of the genome in developing male and female PGCs isolated from mouse embryos. We
      show that DNA methylation erasure is global and affects genes of various
      biological functions. We also reveal complex kinetics of demethylation that are
      initiated at most genes in early PGC precursors around embryonic day 8.0-9.0. In
      addition, besides intracisternal A-particles (IAPs), we identify rare LTR-ERV1
      retroelements and single-copy sequences that resist global methylation erasure in
      PGCs as well as in preimplantation embryos. Our data provide important insights
      into the targets and dynamics of DNA methylation reprogramming in mammalian germ
      cells.

PMID- 22357613
TI  - ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in
      Arabidopsis.
AB  - The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and
      vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia
      mutated [ATM] and Rad3-related) act synergistically to maintain telomere length
      and genome stability in Arabidopsis. Inactivation of ATR, but not ATM,
      temporarily rescued severe morphological phenotypes associated with ctc1 or stn1.
      Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In
      first-generation (G1) ctc1 atr mutants, enhanced telomere attrition was modest,
      but in G2 ctc1 atr, telomeres shortened precipitously, and this loss coincided
      with a dramatic decrease in telomerase activity in G2 atr mutants. Zeocin
      treatment also triggered a reduction in telomerase activity, suggesting that the
      prolonged absence of ATR leads to a hitherto-unrecognized DNA damage response
      (DDR). Finally, our data indicate that ATR modulates DDR in CST mutants by
      limiting chromosome fusions and transcription of DNA repair genes and also by
      promoting programmed cell death in stem cells. We conclude that the absence of
      CST in Arabidopsis triggers a multifaceted ATR-dependent response to facilitate
      maintenance of critically shortened telomeres and eliminate cells with severe
      telomere dysfunction.

PMID- 22357614
TI  - Requirement of translocated lysosomal V1 H(+)-ATPase for activation of membrane
      acid sphingomyelinase and raft clustering in coronary endothelial cells.
AB  - Acid sphingomyelinase (ASM) mediates the formation of membrane raft (MR) redox
      signalosomes in a process that depends on a local acid microenvironment in
      coronary arterial endothelial cells (CAECs). However, it is not known how this
      local acid microenvironment is formed and maintained. The present study
      hypothesized that lysosomal V1 H(+)-ATPase provides a hospitable acid
      microenvironment for activation of ASM when lysosomes traffic and fuse into the
      cell membrane. Confocal microscopy showed that local pH change significantly
      affected MRs, with more fluorescent patches under low pH. Correspondingly, the
      ASM product, ceramide, increased locally in the cell membrane. Electron spin
      resonance assay showed that local pH increase significantly inhibited NADPH
      oxidase-mediated production of O(2)(-.) in CAECs. Direct confocal microscopy
      demonstrated that Fas ligand resulted in localized areas of decreased pH around
      CAEC membranes. The inhibitors of both lysosomal fusion and H(+)-ATPase
      apparently attenuated FasL-caused pH decrease. V1 H(+)-ATPase accumulation and
      activity on cell membranes were substantially suppressed by the inhibitors of
      lysosomal fusion or H(+)-ATPase. These results provide the first direct evidence
      that translocated lysosomal V1 H(+)-ATPase critically contributes to the
      formation of local acid microenvironment to facilitate activation of ASM and
      consequent MR aggregation, forming MR redox signalosomes and mediating redox
      signaling in CAECs.

PMID- 22357615
TI  - Rnd1 and Rnd3 targeting to lipid raft is required for p190 RhoGAP activation.
AB  - The Rnd proteins Rnd1, Rnd2, and Rnd3/RhoE are well known as key regulators of
      the actin cytoskeleton in various cell types, but they comprise a distinct
      subgroup of the Rho family in that they are GTP bound and constitutively active.
      Functional differences of the Rnd proteins in RhoA inhibition signaling have been
      reported in various cell types. Rnd1 and Rnd3 antagonize RhoA signaling by
      activating p190 RhoGAP, whereas Rnd2 does not. However, all the members of the
      Rnd family have been reported to bind directly to p190 RhoGAP and equally induce
      activation of p190 RhoGAP in vitro, and there is no evidence that accounts for
      the functional difference of the Rnd proteins in RhoA inhibition signaling. Here
      we report the role of the N-terminal region in signaling. Rnd1 and Rnd3, but not
      Rnd2, have a KERRA (Lys-Glu-Arg-Arg-Ala) sequence of amino acids in their N
      terminus, which functions as the lipid raft-targeting determinant. The sequence
      mediates the lipid raft targeting of p190 RhoGAP correlated with its activation.
      Overall, our results demonstrate a novel regulatory mechanism by which
      differential membrane targeting governs activities of Rnd proteins to function as
      RhoA antagonists.

PMID- 22357616
TI  - A nucleostemin-like GTPase required for normal apical and floral meristem
      development in Arabidopsis.
AB  - Mammalian nucleostemin (NS) is preferentially expressed in stem cells and acts to
      promote cell cycle progression. In plants, stem cell activities have to be
      terminated during flower development, and this process requires the activation of
      AGAMOUS (AG) gene expression. Here, a nucleostemin-like 1 gene, NSN1, is shown to
      be required for flower development in Arabidopsis. The NSN1 mRNA was found in the
      inflorescence meristem and floral primordia, and its protein was localized to the
      nucleoli. Both heterozygous and homozygous plants developed defective flowers on
      inflorescences that were eventually terminated by the formation of carpelloid
      flowers. Overexpression of NSN1 resulted in loss of apical dominance and
      formation of defective flowers. Expression of the AG gene was found to be up
      regulated in nsn1. The carpelloid flower defect of nsn1 was suppressed by the ag
      mutation in the nsn1 ag double mutant, whereas double mutants of nsn1 apetala2
      (ap2) displayed enhanced defective floral phenotypes. These results suggest that
      in the delicately balanced regulatory network, NSN1 acts to repress AG and plays
      an additive role with AP2 in floral organ specification. As a midsize nucleolar
      GTPase, NSN1 represents a new class of regulatory proteins required for flower
      development in Arabidopsis.

PMID- 22357617
TI  - Reduced expression of MECP2 affects cell commitment and maintenance in neurons by
      triggering senescence: new perspective for Rett syndrome.
AB  - MECP2 protein binds preferentially to methylated CpGs and regulates gene
      expression by causing changes in chromatin structure. The mechanism by which
      impaired MECP2 activity can induce pathological abnormalities in the nervous
      system of patients with Rett syndrome (RTT) is not clearly understood. To gain
      further insight into the role of MECP2 in human neurogenesis, we compared the
      neural differentiation process in mesenchymal stem cells (MSCs) obtained from a
      RTT patient and from healthy donors. We further analyzed neural differentiation
      in a human neuroblastoma cell line carrying a partially silenced MECP2 gene.
      Senescence and reduced expression of neural markers were observed in
      proliferating and differentiating MSCs from the RTT patient, which suggests that
      impaired activity of MECP2 protein may impair neural differentiation, as observed
      in RTT patients. Next, we used an inducible expression system to silence MECP2 in
      neuroblastoma cells before and after the induction of neural differentiation via
      retinoic acid treatment. This approach was used to test whether MECP2
      inactivation affected the cell fate of neural progenitors and/or neuronal
      differentiation and maintenance. Overall, our data suggest that neural cell fate
      and neuronal maintenance may be perturbed by senescence triggered by impaired
      MECP2 activity either before or after neural differentiation.

PMID- 22357618
TI  - MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer
      cells and targets the hedgehog pathway receptor PTCH1.
AB  - Dysexpression of microRNAs has been found in many tumors, including lung cancer.
      The hedgehog (Hh) signaling pathway plays an important role during normal
      development, and the abnormal regulation of its members has also been related to
      many tumors. However, little is known about the relationship between microRNA and
      the Hh pathway. In this paper, we report microRNA-212 (miR-212) playing a role in
      non-small cell lung cancer (NSCLC) and targeting PTCH1, a receptor of the Hh
      pathway. We found that miR-212 was up-regulated when cells were treated with
      4beta-12-O-tetradecanoylphorbol-13-acetate (TPA). We ectopically expressed miR
      212 in NSCLC cell lines to examine the influence of miR-212 overexpression. The
      results showed that overexpression of miR-212 in NSCLC cells promoted cell cycle
      progression and cell proliferation, migration, and invasion. The promoting
      effects of miR-212 on cell proliferation, migration, and invasion were partially
      reversed by the miR-212 inhibitor anti-miR-212. These results suggested that miR
      212 might have tumor-promoting properties. Potential targets of miR-212 were
      predicted, and we showed tumor suppressor PTCH1 was a functional target of miR
      212. PTCH1 may be responsible for the effect of miR-212 on cell proliferation.
      Altogether, our results indicated that miR-212 was involved in tumorigenesis, and
      the oncogenic activity of miR-212 in NSCLC cells was due, in part, to suppression
      of PTCH1.

PMID- 22357619
TI  - Centrosome misorientation mediates slowing of the cell cycle under limited
      nutrient conditions in Drosophila male germline stem cells.
AB  - Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self
      renewal and differentiation. Although asymmetric stem cell division balances
      between self-renewal and differentiation, it does not dictate how frequently
      differentiating cells must be produced. In male GSCs, asymmetric GSC division is
      achieved by stereotyped positioning of the centrosome with respect to the stem
      cell niche. Recently we showed that the centrosome orientation checkpoint
      monitors the correct centrosome orientation to ensure an asymmetric outcome of
      the GSC division. When GSC centrosomes are not correctly oriented with respect to
      the niche, GSC cell cycle is arrested/delayed until the correct centrosome
      orientation is reacquired. Here we show that induction of centrosome
      misorientation upon culture in poor nutrient conditions mediates slowing of GSC
      cell proliferation via activation of the centrosome orientation checkpoint.
      Consistently, inactivation of the centrosome orientation checkpoint leads to lack
      of cell cycle slowdown even under poor nutrient conditions. We propose that
      centrosome misorientation serves as a mediator that transduces nutrient
      information into stem cell proliferation, providing a previously unappreciated
      mechanism of stem cell regulation in response to nutrient conditions.

PMID- 22357620
TI  - Molecular basis for phosphospecific recognition of histone H3 tails by Survivin
      paralogues at inner centromeres.
AB  - Survivin, a subunit of the chromosome passenger complex (CPC), binds the N
      terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and
      localizes the complex to the inner centromeres. We used x-ray crystallography to
      determine the residues of Survivin that are important in binding phosphomodified
      histone H3. Mutation of amino acids that interact with the histone N-terminus
      lowered in vitro tail binding affinity and reduced CPC recruitment to the inner
      centromere in cells, validating our solved structures. Phylogenetic analysis
      shows that nonmammalian vertebrates have two Survivin paralogues, which we name
      class A and B. A distinguishing feature of these paralogues is an H-to-R change
      in an amino acid that interacts with the histone T3 phosphate. The binding to
      histone tails of the human class A paralogue, which has a histidine at this
      position, is sensitive to changes around physiological pH, whereas Xenopus
      Survivin class B is less so. Our data demonstrate that Survivin paralogues have
      different characteristics of phosphospecific binding to threonine-3 of histone
      H3, providing new insight into the biology of the inner centromere.

PMID- 22357621
TI  - Phosphorylation of threonine 1736 in the C-terminal tail of integrin beta4
      contributes to hemidesmosome disassembly.
AB  - During wound healing, hemidesmome disassembly enables keratinocyte migration and
      proliferation. Hemidesmosome dynamics are altered downstream of epidermal growth
      factor (EGF) receptor activation, following the phosphorylation of integrin beta4
      residues S1356 and S1364, which reduces the interaction with plectin; however,
      this event is insufficient to drive complete hemidesmome disassembly. In the
      studies reported here, we used a fluorescence resonance energy transfer-based
      assay to demonstrate that the connecting segment and carboxy-terminal tail of the
      beta4 cytoplasmic domain interact, which facilitates the formation of a binding
      platform for plectin. In addition, analysis of a beta4 mutant containing a
      phosphomimicking aspartic acid residue at T1736 in the C-tail suggests that
      phosphorylation of this residue regulates the interaction with the plectin plakin
      domain. The aspartic acid mutation of beta4 T1736 impaired hemidesmosome
      formation in junctional epidermolysis associated with pyloric atresia/beta4
      keratinocytes. Furthermore, we show that T1736 is phosphorylated downstream of
      protein kinase C and EGF receptor activation and is a substrate for protein
      kinase D1 in vitro and in cells, which requires its translocation to the plasma
      membrane and subsequent activation. In conclusion, we identify T1736 as a novel
      phosphorylation site that contributes to the regulation of hemidesmome
      disassembly, a dynamically regulated process involving the concerted
      phosphorylation of multiple beta4 residues.

PMID- 22357622
TI  - Attenuation of TGF-beta signaling suppresses premature senescence in a p21
      dependent manner and promotes oncogenic Ras-mediated metastatic transformation in
      human mammary epithelial cells.
AB  - The molecular mechanisms that drive triple-negative, basal-like breast cancer
      progression are elusive. Few molecular targets have been identified for the
      prevention or treatment of this disease. Here we developed a series of isogenic
      basal-like human mammary epithelial cells (HMECs) with altered transforming
      growth factor-beta (TGF-beta) sensitivity and different malignancy, resembling a
      full spectrum of basal-like breast carcinogenesis, and determined the molecular
      mechanisms that contribute to oncogene-induced transformation of basal-like HMECs
      when TGF-beta signaling is attenuated. We found that expression of a dominant
      negative type II receptor (DNRII) of TGF-beta abrogated autocrine TGF-beta
      signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12-induced
      senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H
      Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison
      with H-Ras-V12-transformed HMECs that spontaneously escaped H-Ras-V12-induced
      SLGA. Microarray analysis revealed that p21 was the major player mediating Ras
      induced SLGA, and attenuated or loss of p21 expression contributed to the escape
      from SLGA when autocrine TGF-beta signaling was blocked in HMECs. Furthermore,
      knockdown of p21 also suppressed H-Ras-V12-induced SLGA. Our results identify
      that autocrine TGF-beta signaling is an integral part of the cellular anti
      transformation network by suppressing the expression of a host of genes,
      including p21-regulated genes, that mediate oncogene-induced transformation in
      basal-like breast cancer.

PMID- 22357624
TI  - Negative regulation of RhoA translation and signaling by hnRNP-Q1 affects
      cellular morphogenesis.
AB  - The small GTPase RhoA has critical functions in regulating actin dynamics
      affecting cellular morphogenesis through the RhoA/Rho kinase (ROCK) signaling
      cascade. RhoA signaling controls stress fiber and focal adhesion formation and
      cell motility in fibroblasts. RhoA signaling is involved in several aspects of
      neuronal development, including neuronal migration, growth cone collapse,
      dendrite branching, and spine growth. Altered RhoA signaling is implicated in
      cancer and neurodegenerative disease and is linked to inherited intellectual
      disabilities. Although much is known about factors regulating RhoA activity
      and/or degradation, little is known about molecular mechanisms regulating RhoA
      expression and the subsequent effects on RhoA signaling. We hypothesized that
      posttranscriptional control of RhoA expression may provide a mechanism to
      regulate RhoA signaling and downstream effects on cell morphology. Here we
      uncover a cellular function for the mRNA-binding protein heterogeneous nuclear
      ribonucleoprotein (hnRNP) Q1 in the control of dendritic development and focal
      adhesion formation that involves the negative regulation of RhoA synthesis and
      signaling. We show that hnRNP-Q1 represses RhoA translation and knockdown of
      hnRNP-Q1 induced phenotypes associated with elevated RhoA protein levels and
      RhoA/ROCK signaling. These morphological changes were rescued by ROCK inhibition
      and/or RhoA knockdown. These findings further suggest that negative modulation of
      RhoA mRNA translation can provide control over downstream signaling and cellular
      morphogenesis.

PMID- 22357623
TI  - P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during
      cell proliferation.
AB  - The ataxia telangiectasia mutated- and rad3-related kinase (ATR)/Chk1 pathway is
      a sentinel of cell cycle progression. On the other hand, the Ras/mitogen
      activated protein kinase/90-kDa ribosomal S6 kinase (p90 RSK) pathway is a
      central node in cell signaling downstream of growth factors. These pathways are
      closely correlated in cell proliferation, but their interaction is largely
      unknown. Here we show that Chk1 is phosphorylated predominantly at Ser-280 and
      translocated from cytoplasm to nucleus in response to serum stimulation.
      Nonphosphorylated Chk1-Ser-280 mutation attenuates nuclear Chk1 accumulation,
      whereas the phosphomimic mutation has a reverse effect on the localization.
      Treatment with p90 RSK inhibitor impairs Chk1 phosphorylation at Ser-280 and
      accumulation at the nucleus after serum stimulation, whereas these two phenomena
      are induced by the expression of the constitutively active mutant of p90 RSK in
      serum-starved cells. In vitro analyses indicate that p90 RSK stoichiometrically
      phosphorylates Ser-280 on Chk1. Together with Chk1 phosphorylation at Ser-345 by
      ATR and its autophosphorylation at Ser-296, which are critical for checkpoint
      signaling, Chk1-Ser-280 phosphorylation is elevated in a p90 RSK-dependent manner
      after UV irradiation. In addition, Chk1 phosphorylation at Ser-345 and Ser-296
      after UV irradiation is also attenuated by the treatment with p90 RSK inhibitor
      or by Ser-280 mutation to Ala. These results suggest that p90 RSK facilitates
      nuclear Chk1 accumulation through Chk1-Ser-280 phosphorylation and that this
      pathway plays an important role in the preparation for monitoring genetic
      stability during cell proliferation.

PMID- 22357626
TI  - Patient and other factors influencing the prescribing of cardiovascular
      prevention therapy in the general practice setting with and without nurse
      assessment.
AB  - BACKGROUND: Although guidelines indicate when patients are eligible for
      antihypertensives and statins, little is known about whether general
      practitioners (GPs) follow this guidance. OBJECTIVE: To determine the factors
      influencing GPs decisions to prescribe cardiovascular prevention drugs. DESIGN OF
      STUDY: Secondary analysis of data collected on patients whose cardiovascular risk
      factors were measured as part of a controlled study comparing nurse-led risk
      assessment (four practices) with GP-led risk assessment (two practices). SETTING:
      Six general practices in the West Midlands, England. PATIENTS: Five hundred
      patients: 297 assessed by the project nurse, 203 assessed by their GP.
      MEASUREMENTS: Cardiovascular risk factor data and whether statins or
      antihypertensives were prescribed. Multivariable logistic regression models
      investigated the relationship between prescription of preventive treatments and
      cardiovascular risk factors. RESULTS: Among patients assessed by their GP, statin
      prescribing was significantly associated only with a total cholesterol
      concentration >= 7 mmol/L and antihypertensive prescribing only with blood
      pressure >= 160/100 mm Hg. Patients prescribed an antihypertensive by their GP
      were five times more likely to be prescribed a statin. Among patients assessed by
      the project nurse, statin prescribing was significantly associated with age, sex,
      and all major cardiovascular risk factors. Antihypertensive prescribing was
      associated with blood pressures >= 140/90 mm Hg and with 10-year cardiovascular
      risk. LIMITATIONS: Generalizability is limited, as this is a small analysis in
      the context of a specific cardiovascular prevention program. CONCLUSIONS: GP
      prescribing of preventive treatments appears to be largely determined by
      elevation of a single risk factor. When patients were assessed by the project
      nurse, prescribing was much more consistent with established guidelines.

PMID- 22357625
TI  - Mex3c regulates insulin-like growth factor 1 (IGF1) expression and promotes
      postnatal growth.
AB  - Insulin-like growth factor 1 (IGF1) mediates the growth-promoting activities of
      growth hormone. How Igf1 expression is regulated posttranscriptionally is
      unclear. Caenorhabditis elegans muscle excess 3 (MEX-3) is involved in cell fate
      specification during early embryonic development through regulating mRNAs
      involved in specifying cell fate. The function of its mammalian homologue, MEX3C,
      is unknown. Here we show that MEX3C deficiency in Mex3c homozygous mutant mice
      causes postnatal growth retardation and background-dependent perinatal lethality.
      Hypertrophy of chondrocytes in growth plates is significantly impaired.
      Circulating and bone local production of IGF1 are both decreased in mutant mice.
      Mex3c mRNA is strongly expressed in the testis and the brain, and highly
      expressed in resting and proliferating chondrocytes of the growth plates. MEX3C
      is able to enrich multiple mRNA species from tissue lysates, including Igf1. Igf1
      expression in bone is decreased at the protein level but not at the mRNA level,
      indicating translational/posttranslational regulation. We propose that MEX3C
      protein plays an important role in enhancing the translation of Igf1 mRNA, which
      explains the perinatal lethality and growth retardation observed in MEX3C
      deficient mice.

PMID- 22357627
TI  - Evaluation of 19 susceptibility loci of breast cancer in women of African
      ancestry.
AB  - Multiple breast cancer susceptibility loci have been identified in genome-wide
      association studies (GWAS) in populations of European and Asian ancestry using
      array chips optimized for populations of European ancestry. It is important to
      examine whether these loci are associated with breast cancer risk in women of
      African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19
      loci in a pooled case-control study of breast cancer, which included 1509 cases
      and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the
      USA; all women were of African ancestry. We found significant associations for
      three SNPs, which were in the same direction and of similar magnitude as those
      reported in previous fine-mapping studies in women of African ancestry. The
      allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P =
      0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P =
      0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04)
      for the rs3104793-C allele (16q12). Although a significant association was
      observed for an additional index SNP (rs3817198), it was in the opposite
      direction to prior GWAS studies. In conclusion, this study highlights the
      complexity of applying current GWAS findings across racial/ethnic groups, as none
      of GWAS-identified index SNPs could be replicated in women of African ancestry.
      Further fine-mapping studies in women of African ancestry will be needed to
      reveal additional and causal variants for breast cancer.

PMID- 22357628
TI  - Tcra enhancer activation by inducible transcription factors downstream of pre-TCR
      signaling.
AB  - The Tcra enhancer (Ealpha) is essential for pre-TCR-mediated activation of
      germline transcription and V(D)J recombination. Ealpha is considered an
      archetypical enhanceosome that acts through the functional synergy and
      cooperative binding of multiple transcription factors. Based on dimethylsulfate
      genomic footprinting experiments, there has been a long-standing paradox
      regarding Ealpha activation in the absence of differences in enhancer occupancy.
      Our data provide the molecular mechanism of Ealpha activation and an explanation
      of this paradox. We found that germline transcriptional activation of Tcra is
      dependent on constant phospholipase Cgamma, as well as calcineurin- and MAPK/ERK
      mediated signaling, indicating that inducible transcription factors are crucially
      involved. NFAT, AP-1, and early growth response factor 1, together with CREB
      binding protein/p300 coactivators, bind to Ealpha as part of an active
      enhanceosome assembled during pre-TCR signaling. We favor a scenario in which the
      binding of lymphoid-restricted and constitutive transcription factors to Ealpha
      prior to its activation forms a regulatory scaffold to recruit factors induced by
      pre-TCR signaling. Thus, the combinatorial assembly of tissue- and signal
      specific transcription factors dictates the Ealpha function. This mechanism for
      enhancer activation may represent a general paradigm in tissue-restricted and
      stimulus-responsive gene regulation.

PMID- 22357629
TI  - Lymphotoxin beta receptor activation on macrophages induces cross-tolerance to
      TLR4 and TLR9 ligands.
AB  - Our previous studies indicated that lymphotoxin beta receptor (LTbetaR)
      activation controls and downregulates inflammatory reactions. In this study, we
      report that LTbetaR activation on primary mouse macrophages results in induction
      of tripartite motif containing (TRIM) 30alpha, which negatively regulates NF
      kappaB activation induced by TLR signaling. LTbetaR activation results in a
      downregulation of proinflammatory cytokine and mediator expression upon TLR
      restimulation, demonstrating that LTbetaR signaling is involved in the induction
      of TLR cross-tolerance. Specific knockdown experiments using TRIM30alpha-specific
      small interfering RNA abolished the LTbetaR-dependent induction of TRIM30alpha
      and LTbetaR-mediated TLR cross-tolerance. Concordantly, LTbetaR activation on
      bone marrow-derived macrophages induced cross-tolerance to TLR4 and TLR9 ligands
      in vitro. Furthermore, we have generated cell type-specific LTbetaR-deficient
      mice with ablation of LTbetaR expression on macrophages/neutrophils
      (LTbetaR(flox/flox) * LysM-Cre). In bone marrow-derived macrophages derived from
      these mice LTbetaR-induced cross-tolerance to TLR4 and TLR9 ligands was impaired.
      Additionally, mice with a conditional ablation of LTbetaR expression on
      macrophages (LTbetaR(flox/flox) * LysM-Cre) are resistant to LTbetaR-induced TLR4
      tolerance in vivo. Collectively, our data indicate that LTbetaR activation on
      macrophages by T cell-derived lymphotoxin alpha(1)beta(2) controls
      proinflammatory responses by activation of a TRIM30alpha-controlled,
      counterregulatory signaling pathway to protect against exacerbating inflammatory
      reactions.

PMID- 22357630
TI  - Francisella tularensis inhibits the intrinsic and extrinsic pathways to delay
      constitutive apoptosis and prolong human neutrophil lifespan.
AB  - Francisella tularensis is a facultative intracellular bacterium that infects many
      cell types, including neutrophils. We demonstrated previously that F. tularensis
      inhibits NADPH oxidase assembly and activity and then escapes the phagosome to
      the cytosol, but effects on other aspects of neutrophil function are unknown.
      Neutrophils are short-lived cells that undergo constitutive apoptosis, and
      phagocytosis typically accelerates this process. We now demonstrate that F.
      tularensis significantly inhibited neutrophil apoptosis as indicated by
      morphologic analysis as well as annexin V and TUNEL staining. Thus, ~80% of
      infected neutrophils remained viable at 48 h compared with ~50% of control cells,
      and ~40% of neutrophils that ingested opsonized zymosan. In keeping with this
      finding, processing and activation of procaspases-8, -9, and -3 were markedly
      diminished and delayed. F. tularensis also significantly impaired apoptosis
      triggered by Fas crosslinking. Of note, these effects were dose dependent and
      could be conferred by either intracellular or extracellular live bacteria, but
      not by formalin-killed organisms or isolated LPS and capsule, and were not
      affected by disruption of wbtA2 or FTT1236/FTL0708-genes required for LPS O
      antigen and capsule biosynthesis. In summary, we demonstrate that F. tularensis
      profoundly impairs constitutive neutrophil apoptosis via effects on the intrinsic
      and extrinsic pathways, and thereby define a new aspect of innate immune evasion
      by this organism. As defects in neutrophil turnover prevent resolution of
      inflammation, our findings also suggest a mechanism that may in part account for
      the neutrophil accumulation, granuloma formation, and severe tissue damage that
      characterizes lethal pneumonic tularemia.

PMID- 22357632
TI  - Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation
      of T cell responses.
AB  - Galectins, a family of mammalian lectins, have emerged as key regulators of the
      immune response. We previously demonstrated that galectin (Gal)-8, from the
      tandem-repeat subgroup, exerts two well-defined effects on mouse naive peripheral
      CD4 T cells: Ag-specific costimulation and Ag-independent proliferation. These
      stimulatory signals on naive T cells have not been described for any other Gal.
      Therefore, we investigated whether Gal-1 and Gal-3, two prominent members of the
      Gal family, share the stimulatory effects exerted by Gal-8 on naive T cells. We
      found that Gal-1 costimulated Ag-specific T cell responses similarly to Gal-8, as
      evaluated in the DO11.10 TCR(OVA)-transgenic mouse model, by acting
      simultaneously on APCs and target CD4 T cells. In contrast, Gal-3 failed to
      costimulate Ag-specific T cell responses; moreover, it antagonized both Gal-1 and
      Gal-8 signals. We observed that both Gal-1 and Gal-3 were unable to induce Ag
      independent proliferation; however, when two Gal-1 molecules were covalently
      fused, the resulting chimeric protein efficiently promoted proliferation. This
      finding indicates that Gal-1 might eventually induce proliferation and, moreover,
      stresses the requirement of a tandem-repeat structure. Remarkably, a single dose
      of recombinant Gal-1 or Gal-8 administered together with a suboptimal Ag dose to
      DO11.10 mice strengthened weak responses in vivo. Taken together, these findings
      argue for the participation of Gals in the initiation of the immune response and
      allow the postulation of these lectins as enhancers of borderline Ag responses,
      thus representing potential adjuvants for vaccine formulations.

PMID- 22357631
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin induces transcriptional activity of the human
      polymorphic hs1,2 enhancer of the 3'Igh regulatory region.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant known to
      inhibit Ab secretion and Ig expression. Inhibition of Ig expression may be
      partially mediated through repression of the 3'Igh regulatory region (3'IghRR).
      TCDD inhibits mouse 3'IghRR activation and induces aryl hydrocarbon receptor
      binding to dioxin response elements within the 3'IghRR enhancers hs1,2 and hs4.
      The human hs1,2 enhancer (hu-hs1,2) is polymorphic as the result of the presence
      of one to four invariant sequences (ISs), which have been correlated with several
      autoimmune diseases. The IS also contains a dioxin response element core motif.
      Therefore, the objective was to determine whether hu-hs1,2 activity is sensitive
      to TCDD. Using a mouse B cell line (CH12.LX), we compared the effects of TCDD on
      mouse hs1,2 versus hu-hs1,2 activity. TCDD inhibited mouse hs1,2 similarly to the
      mouse 3'IghRR. In contrast, hu-hs1,2 was activated by TCDD, and antagonist
      studies supported an aryl hydrocarbon receptor-dependent activation, which was
      replicated in a human B cell line (IM-9). Absence of Pax5 binding sites is a
      major difference between the human and mouse hs1,2 sequence. Insertion of the
      high-affinity Pax5 site in hu-hs1,2 markedly blunted reporter activity but did
      not alter TCDD's effect (i.e., no shift from activation to inhibition).
      Additionally, deletional analysis demonstrated a significant IS contribution to
      hu-hs1,2 basal activity, but TCDD-induced activity was not strictly IS number
      dependent. Taken together, our results suggest that hu-hs1,2 is a significant
      target of TCDD and support species differences in hs1,2 regulation. Therefore,
      sensitivity of hu-hs1,2 to chemical-induced modulation may influence the
      occurrence and/or severity of human diseases associated with hu-hs1,2.

PMID- 22357633
TI  - Differential effects of power training versus functional task practice on
      compensation and restoration of arm function after stroke.
AB  - BACKGROUND: Improved upper-extremity (UE) movement with stroke rehabilitation may
      involve restoration of more normal or development of compensatory movement
      patterns. OBJECTIVE: The authors investigated the differential effects of
      functional task practice (FTP) and dynamic resistance training (POWER) on
      clinical function and reaching kinematics in an effort to distinguish between
      mechanisms of gains. METHODS: A total of 14 hemiparetic individuals were randomly
      assigned to 10 weeks of either FTP or POWER and then crossed over to 10 weeks of
      the alternate treatment. Treatment order A was FTP followed by POWER, whereas
      treatment order B was POWER followed by FTP. Evaluation before and after each
      treatment block included a battery of clinical evaluations and kinematics of
      paretic UE functional reach to grasp. RESULTS: Both FTP and POWER improved
      movement accuracy, as revealed by a shift toward normal, including fewer
      submovements and reduced reach-path ratio. However, active range of motion
      revealed differential treatment effects. Shoulder flexion and elbow extension
      decreased with FTP and were associated with increased trunk displacement. In
      contrast, shoulder flexion and elbow extension excursion increased with POWER and
      were associated with significantly reduced trunk displacement. Treatment order B
      (POWER followed by FTP) revealed greater overall improvements. CONCLUSION: FTP
      increases compensatory movement patterns to improve UE function. POWER leads to
      more normal movement patterns. POWER prior to FTP may enhance the benefits of
      repetitive task practice.

PMID- 22357634
TI  - A perfusion fMRI study of the neural correlates of sustained-attention and
      working-memory deficits in chronic traumatic brain injury.
AB  - BACKGROUND: Given that traumatic brain injury (TBI) results in chronic alteration
      of baseline cerebral perfusion, a perfusion functional MRI (fMRI) method that
      dissociates resting- and task-related cerebral blood flow (CBF) changes can be
      useful in noninvasively investigating the neural correlates of cognitive
      dysfunction and recovery in TBI. OBJECTIVE: The authors used continuous arterial
      spin-labeled (ASL) perfusion fMRI to characterize CBF at rest and during
      sustained-attention and working-memory tasks. METHODS: A total of 18 to 21
      individuals with moderate to severe TBI and 14 to 18 demographically matched
      healthy controls completed 3 continuous 6-minute perfusion fMRI scans (resting,
      visual sustained attention, and 2-back working memory). RESULTS: For both tasks,
      TBI participants showed worse behavioral performance than controls. Voxelwise
      neuroimaging analysis of the 2-back task found that group differences in task
      induced CBF changes were localized to bilateral superior occipital cortices and
      the left superior temporal cortex. Whereas controls deactivated these areas
      during task performance, TBI participants tended to activate these same areas.
      These regions were among those found to be disproportionately hypoperfused at
      rest after TBI. For both tasks, the control and TBI groups showed different
      patterns of correlation between performance and task-related CBF changes.
      CONCLUSIONS: ASL perfusion fMRI demonstrated differences between individuals with
      TBI and healthy controls in resting perfusion and in task-evoked CBF changes as
      well as different patterns of performance-activation correlation. These results
      are consistent with the notion that sensory/attentional modulation deficits
      contribute to higher cognitive dysfunction in TBI.

PMID- 22357636
TI  - Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome
      malformations in proprotein convertase 4 (PCSK4) null mice.
AB  - Proprotein convertase 4 (PCSK4) is a member of a family of proprotein convertases
      that convert inactive precursor proteins into their mature and active forms.
      PCSK4 is expressed by testicular germ cells and localizes to the sperm acrosome,
      suggesting roles in fertilization. Mice lacking PCSK4 exhibit a profound
      fertility defect; yet, to date, few substrates for PCSK4 are known. In this
      study, two-dimensional differential in-gel electrophoresis analysis was carried
      out in order to identify proteins that are altered in spermatozoa from PCSK4 null
      mice. Herein, we report that the sperm fertilization molecule acrosin-binding
      protein (ACRBP)/sp32, which normally undergoes processing from a 58.5 kDa
      precursor to a 27.5 kDa mature form, is not proteolytically processed in PCSK4
      null mice and thus may be a substrate for PCSK4. However, analysis of the ACRBP
      sequence did not show a strong consensus site for convertase cleavage, suggesting
      that ACRBP processing may require the activity of a yet unknown enzyme that
      itself may be a PCSK4 substrate. Further analysis of spermatozoa from the PCSK4
      null mice showed that proacrosin did not undergo autoactivation, supporting a
      role for the mature form of ACRBP in the regulation of proacrosin conversion into
      different acrosin isoforms. Finally, examination of ACRBP localization revealed a
      previously undetected morphological defect in the head/acrosomes of spermatozoa
      from PCSK4 null mice. Taken together, these results demonstrate that the
      fertility defect in the PCSK4 null mice may in part be due to altered ACRBP
      protein processing as well as abnormalities in the sperm head/acrosome.

PMID- 22357635
TI  - The ubiquitin-proteasome system meets angiogenesis.
AB  - A strict physiological balance between endogenous proangiogenic and
      antiangiogenic factors controls endothelial cell functions, such that endothelial
      cell growth is normally restrained. However, in pathologic angiogenesis, a shift
      occurs in the balance of regulators, favoring endothelial growth. Much of the
      control of angiogenic events is instigated through hypoxia-induced VEGF
      expression. The ubiquitin-proteasome system (UPS) plays a central role in fine
      tuning the functions of core proangiogenic proteins, including VEGF, VEGFR-2,
      angiogenic signaling proteins (e.g., the PLCgamma1 and PI3 kinase/AKT pathways),
      and other non-VEGF angiogenic pathways. The emerging mechanisms by which
      ubiquitin modification of angiogenic proteins control angiogenesis involve both
      proteolytic and nonproteolytic functions. Here, I review recent advances that
      link the UPS to regulation of angiogenesis and highlight the potential
      therapeutic value of the UPS in angiogenesis-associated diseases.

PMID- 22357637
TI  - Pemetrexed-induced cellulitis: a rare toxicity in non-small cell lung cancer
      treatment.
AB  - Pemetrexed is indicated for locally advanced or metastatic non-squamous non-small
      cell lung cancer as an initial treatment in combination with cisplatin or after
      prior chemotherapy as a single agent. It is generally a well-tolerated drug. The
      most common adverse reactions (incidence >= 20%) with single-agent use are
      fatigue, nausea, and anorexia. Additional common side effects when used in
      combination with cisplatin include vomiting, neutropenia, leukopenia, anemia,
      stomatitis/pharyngitis, thrombocytopenia, and constipation. Peripheral edema with
      associated erythema has rarely been described as an adverse effect. Herein, we
      report a patient with advanced non-small-cell lung cancer who experienced
      bilateral peripheral edema after pemetrexed administration. Discontinuation of
      pemetrexed and corticosteroids use completely resolved peripheral edema.

PMID- 22357638
TI  - Cost-effectiveness of fulvestrant 250 mg versus 500 mg in postmenopausal women
      with estrogen receptor-positive metastatic breast cancer and disease progression
      after antiestrogen therapy.
AB  - PURPOSE: To determine the cost-effectiveness of fulvestrant 250 mg compared to
      500 mg in postmenopausal women with estrogen receptor-positive metastatic breast
      cancer and disease progression after antiestrogen therapy. METHODS: A Markov
      model was constructed to find the incremental cost-effectiveness of fulvestrant
      250 mg monthly when compared with the 500 mg monthly in patients with progression
      after antiestrogen therapy. The model duration was 24 months. Clinical efficacy
      data inputs were derived from a phase III clinical trial demonstrating a
      statistically significant increase in progression-free survival in patients
      receiving 500 mg versus 250 mg. Cost data utilized were all relevant Ambulatory
      Payment Classification payment rates from the 2011 Medicare Outpatient
      Prospective Payment System. A Monte Carlo simulation was performed to test the
      model at various willingness to pay thresholds. RESULTS: The incremental cost
      effectiveness ratio as determined by the Markov model was US$10,972 per month of
      progression-free survival for the 500 mg dose compared with the 250 mg dose.
      Using a Monte Carlo simulation, it was found that 500 mg monthly was cost
      effective at and above the willingness to pay threshold of US$15,000 per month. A
      series of one-way sensitivity analyses showed this result is robust to
      geographical practice variations in costs of drug administration and physician
      examination. CONCLUSION: From a third party payer perspective, the value of
      fulvestrant 500 mg monthly is dependent on the willingness to pay threshold.
      Despite a labeling change for fulvestrant in September 2010, fulvestrant 250 mg
      monthly appears to be a viable option in the target population.

PMID- 22357639
TI  - Impacts of suppression on emotional responses and performance outcomes: an
      experience-sampling study in younger and older workers.
AB  - OBJECTIVES: Past studies have demonstrated that older adults used less emotional
      suppression to regulate their emotions than did younger adults, but the
      effectiveness of using this emotion regulatory strategy on psychosocial well
      being across age remains largely unexplored. The present study adopted an
      experience-sampling method to examine whether the impacts of momentary employment
      of emotional suppression on momentary positive and negative emotions and job
      performance would be different by age. METHOD: Eighty-seven Chinese insurance
      workers, aged between 18 and 61 years, participated in a 5-day sampling study.
      Their affective responses at work, momentary task performance, and sales
      productivity were recorded. RESULTS: Results showed that older workers' greater
      use of suppression at work was associated with lower intensity of negative
      emotions, whereas such association was not found among younger workers. Moreover,
      greater use of suppression over the sampling period was significantly predictive
      of sales productivity of older workers, but such a positive association was not
      shown in younger workers. DISCUSSION: These findings reveal that the use of
      suppression at work may be more effective for older workers than for younger
      workers.

PMID- 22357640
TI  - Solidarity and ambivalence: comparing two perspectives on intergenerational
      relations using longitudinal panel data.
AB  - OBJECTIVES: Research on family relations has extensively used the
      intergenerational solidarity model proposed by Bengtson and colleagues. Recently,
      the relevance of this model for explaining changes in family relations has been
      questioned, and the concept of intergenerational ambivalence has been proposed as
      a relevant addition to the model, supposedly acting as a catalyst, and thus
      serving as an explanation for changes in family relations. This study tests both
      the viability of the intergenerational solidarity model and the hypothesized
      effect of ambivalence employing longitudinal data. METHOD: We use data from 2
      waves of the Netherlands' Kinship Panel Study on parent-adult child relationships
      to estimate latent variable structural equation models. RESULTS: Affection,
      association, and support between family members are core, mutually reinforcing
      dimensions of solidarity. The hypothesis that ambivalence is a catalyst for
      change in family relations was not confirmed. Adding conflict separately revealed
      that it only affects the core solidarity dimensions but is itself, like normative
      and structural solidarity, not influenced by them. DISCUSSION: The relevance of
      the concept of intergenerational ambivalence for studying changes in family
      relations can be questioned. The viability of the intergenerational solidarity
      model is, however, confirmed. The concept of intergenerational ambivalence might
      be further explored in qualitative studies on family change.

PMID- 22357641
TI  - Personality stability is associated with better cognitive performance in
      adulthood: are the stable more able?
AB  - OBJECTIVES: Although personality is relatively stable over time, there are
      individual differences in the patterns and magnitude of change. There is some
      evidence that personality change in adulthood is related to physical health and
      longevity. The present study expanded this work to consider whether personality
      stability or change would be associated with better cognitive functioning,
      especially in later adulthood. METHOD: A total of 4,974 individuals participated
      in two waves of The Midlife in the United States Study (MIDUS) in 1994-1995 and
      2004-2005. Participants completed the MIDUS personality inventory at both times
      and the Brief Test of Adult Cognition by Telephone cognitive battery at Time 2.
      RESULTS: Multiple regression and analysis of covariance analyses showed that,
      consistent with predictions, individuals remaining stable in openness to
      experience and neuroticism had faster reaction times and better inductive
      reasoning than those who changed. Among older adults, those who remained stable
      or decreased in neuroticism had significantly faster reaction times than those
      who increased. CONCLUSIONS: As predicted, personality stability on some traits
      was associated with more adaptive cognitive performance on reasoning and reaction
      time. Personality is discussed as a possible resource for protecting against or
      minimizing age-related declines in cognition.

PMID- 22357642
TI  - Idea density measured in late life predicts subsequent cognitive trajectories:
      implications for the measurement of cognitive reserve.
AB  - OBJECTIVE: The Nun Study showed that lower linguistic ability in young adulthood,
      measured by idea density (ID), increased the risk of dementia in late life. The
      present study examined whether ID measured in late life continues to predict the
      trajectory of cognitive change. METHOD: ID was measured in 81 older adults who
      were followed longitudinally for an average of 4.3 years. Changes in global
      cognition and 4 specific neuropsychological domains (episodic memory, semantic
      memory, spatial abilities, and executive function) were examined as outcomes.
      Separate random effects models tested the effect of ID on longitudinal change in
      outcomes, adjusted for age and education. RESULTS: Lower ID was associated with
      greater subsequent decline in global cognition, semantic memory, episodic memory,
      and spatial abilities. When analysis was restricted to only participants without
      dementia at the time ID was collected, results were similar. DISCUSSION:
      Linguistic ability in young adulthood, as measured by ID, has been previously
      proposed as an index of neurocognitive development and/or cognitive reserve. The
      present study provides evidence that even when ID is measured in old age, it
      continues to be associated with subsequent cognitive decline and as such may
      continue to provide a marker of cognitive reserve.

PMID- 22357644
TI  - Nasopharyngeal biofilm-producing otopathogens in children with nonsevere
      recurrent acute otitis media.
AB  - OBJECTIVE: Bacterial biofilms have been detected in biopsies of the adenoid and
      middle ear mucosa of otitis-prone children and children with chronic middle
      otitis media. However, the invasiveness of biopsy makes it unsuitable for routine
      clinical practice, especially in pediatrics. This study aimed to investigate
      nasopharyngeal biofilm-producing otopathogens (BPOs) of nasopharyngeal swabs
      (NPS) in children with a history of nonsevere recurrent acute otitis media (RAOM)
      and healthy controls. STUDY DESIGN: A cross-sectional study with planned data
      collection. SETTING: University of Milan. SUBJECTS AND METHODS: Transoral NPS
      were taken from infants and children aged 10 months to 11 years with nonsevere
      RAOM or healthy controls without adenoid hypertrophy. Nasopharyngeal colonization
      by otopathogens was assessed by means of microbiological cultures and standard
      bacterial identification, as well as nasopharyngeal BPOs by means of
      spectrophotometric analysis. RESULTS: The study involved 113 children (56.6%
      males; median age 40 months; range, 10-132 months): 58 with a history of
      nonsevere RAOM (51.3%) and 55 controls (48.7%). Otopathogens were significantly
      more frequently detected in the RAOM group (24/58, 41.4%) than in controls (8/55,
      14.5%; P = .003); the main pathogens were respectively Haemophilus influenzae
      (12/24, 50.0%) and Streptococcus pyogenes (3/8, 37.5%). Nasopharyngeal BPOs were
      more frequently isolated in the RAOM group (17/58, 29.3%) than in controls (6/55,
      10.9%; P = .02). H influenzae (12/17, 70.6%) was confirmed as the main pathogen
      in the RAOM group. CONCLUSION: The presence of nasopharyngeal BPOs is an
      important factor favoring RAOM; it is therefore useful investigating biofilms
      even in children with nonsevere recurrences of AOM without adenoid hypertrophy.

PMID- 22357643
TI  - History of sexual assault is associated with greater declines in executive
      functioning in older adults with APOE epsilon4.
AB  - OBJECTIVES: This study examined the longitudinal association between a prior
      history of sexual assault (SA), typically in youth, and decreasing executive
      functioning (EF) in old age and whether the apolipoprotein (APOE) epsilon4 allele
      modifies this relationship. METHOD: In this longitudinal study, 846 community
      dwelling older adults at baseline completed questions about SA history and two
      tests of EF. Over the 10 years following this baseline visit, participants
      completed up to 3 follow-up cognitive assessments. Mixed-effects models first
      examined the longitudinal association between SA and EF performance. Last,
      preplanned analyses examined whether the APOE epsilon4 allele modified this
      association. RESULTS: A single SA exposure was not associated with EF declines.
      Repeated SA exposure was associated with steeper declines in both EF measures.
      For Trails B, there was a significant interaction between any SA exposure and the
      APOE epsilon4 allele, such that having either repeated or isolated SA as well as
      APOE epsilon4 was associated with faster decline. DISCUSSION: SA exposure earlier
      in life may increase risk for declines in EF 50-60 years later in old age,
      particularly in the context of the APOE epsilon4 allele. These results generally
      support a diathesis-stress model of decreased cognitive reserve.

PMID- 22357645
TI  - Prognostic value of cartilage sclerosis in laryngeal cancer treated with primary
      radiation therapy.
AB  - OBJECTIVE: In patients with laryngeal cancer, pretreatment diagnosis of cartilage
      invasion often warrants a surgical or a bimodal treatment. Controversy exists on
      whether laryngeal cartilage sclerosis on computed tomography (CT) scan is a sign
      of tumor invasion. Our objective is to evaluate locoregional, laryngectomy-free,
      disease-specific, and overall survival in patients with laryngeal cancer with or
      without laryngeal cartilage sclerosis treated with primary radiation therapy.
      STUDY DESIGN: Historical cohort study. SETTING: Tertiary referral university
      center. SUBJECTS AND METHODS: All laryngeal cancer patients treated with primary
      radiation therapy between 2002 and 2007 were included. Patients with and without
      laryngeal cartilage sclerosis on CT scan were identified. Patient, tumor, and
      treatment data were collected. Univariate and multivariate analyses were
      conducted using Kaplan-Meier survival analyses and Cox proportional-hazards
      regression. RESULTS: One hundred eleven patients were included for analysis.
      Seventy-nine patients were classified as T1 or T2, and 32 patients were
      classified as T3 or T4. Twenty-three percent of patients had any laryngeal
      cartilage sclerosis, and 77% of patients had no sclerosis. On univariate and
      multivariate analyses, there was no statistically significant difference between
      patients with or without sclerosis. Results did not vary when studying each
      cartilage separately. CONCLUSION: Laryngeal cancer patients with cartilage
      sclerosis on CT scan do not have significantly different survival than patients
      without sclerosis. Validation of these results prospectively is warranted.

PMID- 22357646
TI  - Age-related differences in patterns of increased Bordetella pertussis antibodies.
AB  - During the period 2008 to 2010, we identified 11,386 serum samples with increased
      (positive) levels of antibodies recognizing Bordetella pertussis antigens. We
      sought to characterize the distribution of positive antibody result patterns in
      relation to patient age. IgG and IgA antibodies recognizing pertussis toxin (PT)
      and filamentous hemagglutinin (FHA) were quantified using a multianalyte
      immunodetection assay. Four mutually exclusive positive result patterns were
      observed: increased FHA antibodies only, increased PT IgA but not IgG, increased
      PT IgG but not IgA, and increased PT IgG and IgA. In patients < 21 years old, the
      predominant pattern was increased PT IgG but not IgA, whereas in patients >= 21
      years old, it was increased FHA antibodies only. The proportion of positive serum
      samples exhibiting increased PT IgA but not IgG was < 20% in all age categories
      but showed a stepwise rise with age. The proportions of positive serum samples
      exhibiting increased PT IgG and IgA were similar (26 to 32%) in the age
      categories spanning 11 to 60 years of age but lower in the < 11- and > 60-year
      old groups. In 3 of 5 age categories, a significant rise in the proportion of
      positive serum samples exhibiting increased FHA antibodies only occurred in 2010.
      Patterns of positive B. pertussis antibody results varied with age. The
      predominance of increased FHA antibodies only in patients > 20 years old suggests
      that many adults thought to have B. pertussis infections actually have other
      infections that induce FHA-reactive antibodies. Similarly, the 2010 rise in the
      frequency of increased FHA antibodies only in some age groups suggests an
      increase in non-B. pertussis infections.

PMID- 22357647
TI  - Assessment of potential cross-reactivity of human endogenous matrix
      metalloproteinases with collagenase Clostridium histolyticum antibodies in human
      sera obtained from patients with Dupuytren's contracture.
AB  - Collagenase Clostridium histolyticum (CCH) contains a fixed ratio of class I (AUX
      I) and class II (AUX-II) collagenases and is used as treatment for Dupuytren's
      contracture. These two Zn-dependent enzymes, produced by the Gram-positive
      bacterium Clostridium histolyticum, are related functionally to matrix
      metalloproteinases (MMPs) which, among other functions, degrade the extracellular
      matrix. Since AUX-I and AUX-II exhibit sequence similarities to human MMPs, we
      assessed MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3
      (stromelysin 1), MMP-8 (collagenase 2), and MMP-13 (collagenase 3) for cross
      reactivity with anti-AUX-I and anti-AUX-II antibodies in patient serum. Serum
      samples from 71 subjects enrolled in a long-term clinical study (58 males and 13
      females; 63 +/- 10 years old [mean +/- standard error]) were evaluated for cross
      reactivity with the five MMPs using the two validated enzyme-linked immunosorbent
      assays (ELISAs). Inhibition cutoff points for anti-AUX-I and anti-AUX-II
      antibodies were based on assay inhibition obtained with a nonspecific protein,
      bovine gamma globulin, which was tested for each clinical sample. No MMP cross
      reactivity was found for any of the 71 clinical antibody-positive sera evaluated.
      Sequence identity assessments indicated minimal, nonmeaningful alignments of the
      MMPs and AUX-I/AUX-II. Furthermore, clinical adverse event assessments indicated
      no safety signals related to MMP inhibition. The bioanalytical results, sequence
      identity, and clinical assessments consistently did not demonstrate cross
      reactivity between CCH antidrug antibodies and endogenous human matrix
      metalloproteinases. The results presented here suggest that treatment of
      Dupuytren's contracture patients with CCH does not lead to any clinical adverse
      events associated with MMP inhibition.

PMID- 22357648
TI  - Serodiagnosis efficacy and immunogenicity of the fusion protein of Mycobacterium
      tuberculosis composed of the 10-kilodalton culture filtrate protein, ESAT-6, and
      the extracellular domain fragment of PPE68.
AB  - In order to identify immunodominant antigens of Mycobacterium tuberculosis that
      may be used in the serodiagnosis of active tuberculosis (TB), we designed an M.
      tuberculosis fusion protein consisting of CFP-10 (10-kDa culture filtrate
      protein), ESAT-6 (6-kDa early secreted antigenic target), and the extracellular
      domain fragment of PPE68 (PPE68'). Then, the coding sequences of the three
      proteins were inserted into a prokaryotic expression vector, pET-32a(+). To
      enhance the immunological response, the proteins were linked together. The fusion
      proteins with a 6 * His tag were successfully overexpressed in Escherichia coli
      BL21 and purified. The purified proteins were applied for detection of the total
      IgG titer by using an enzyme-linked immunosorbent assay (ELISA) with human sera
      from well-characterized TB cases and the control cases, and results were compared
      to those with purified protein derivative tuberculin (PPD). The ELISA results
      showed that among 140 cases of confirmed active TB and 70 control cases, CFP-10
      ESAT-6-PPE68' had a sensitivity of 73.3% and specificity of 94.3%, compared to a
      sensitivity of 66.7% and specificity of 74.3% for PPD and a sensitivity of 65%
      and specificity of 91.4% for CFP-10-ESAT-6. In addition, the fusion protein CFP
      10-ESAT-6-PPE68' stimulated a higher level of antigen-specific gamma interferon
      (IFN-gamma) release for active-TB patients than PPD and CFP-10-ESAT-6. After
      immunization of C57BL/6 mice, the findings indicated that the total IgG titers
      and the concentrations of IFN-gamma in mice immunized by CFP-10-ESAT-6-PPE68'
      were high and induced strong, long-term humoral immunity compared to results with
      PPD and CFP-10-ESAT-6. Thus, our study indicates that the fusion protein CFP-10
      ESAT-6-PPE68' may be useful as an immunodominant antigen for the serodiagnosis of
      active TB.

PMID- 22357650
TI  - Case report of the reliability 1,3-beta-D-glucan monitoring during treatment of
      peritoneal candidiasis in a child receiving continuous peritoneal dialysis.
AB  - Fungal peritonitis is an unusual but severe complication of continuous peritoneal
      dialysis. The role of 1,3-beta-D-glucan is unknown in early diagnosis and in
      treatment monitoring of peritoneal candidiasis. This case report shows the
      utility of 1,3-beta-D-glucan monitoring in management of Candida peritonitis in a
      child undergoing continuous peritoneal dialysis.

PMID- 22357649
TI  - Lactobacillus acidophilus induces cytokine and chemokine production via NF-kappaB
      and p38 mitogen-activated protein kinase signaling pathways in intestinal
      epithelial cells.
AB  - Intestinal epithelial cells can respond to certain bacteria by producing an array
      of cytokines and chemokines which are associated with host immune responses.
      Lactobacillus acidophilus NCFM is a characterized probiotic, originally isolated
      from human feces. This study aimed to test the ability of L. acidophilus NCFM to
      stimulate cytokine and chemokine production in intestinal epithelial cells and to
      elucidate the mechanisms involved in their upregulation. In experiments using
      intestinal epithelial cell lines and mouse models, we observed that L.
      acidophilus NCFM could rapidly but transiently upregulate a number of effector
      genes encoding cytokines and chemokines such as interleukin 1alpha (IL-1alpha),
      IL-1beta, CCL2, and CCL20 and that cytokines showed lower expression levels with
      L. acidophilus NCFM treatment than chemokines. Moreover, L. acidophilus NCFM
      could activate a pathogen-associated molecular pattern receptor, Toll-like
      receptor 2 (TLR2), in intestinal epithelial cell lines. The phosphorylation of NF
      kappaB p65 and p38 mitogen-activated protein kinase (MAPK) in intestinal
      epithelial cell lines was also enhanced by L. acidophilus NCFM. Furthermore,
      inhibitors of NF-kappaB (pyrrolidine dithiocarbamate [PDTC]) and p38 MAPK
      (SB203580) significantly reduced cytokine and chemokine production in the
      intestinal epithelial cell lines stimulated by L. acidophilus NCFM, suggesting
      that both NF-kappaB and p38 MAPK signaling pathways were important for the
      production of cytokines and chemokines induced by L. acidophilus NCFM.

PMID- 22357652
TI  - CD46 measles virus receptor polymorphisms influence receptor protein expression
      and primary measles vaccine responses in naive Australian children.
AB  - Despite the availability of measles vaccines, infants continue to die from
      measles. Measles vaccine responses vary between individuals, and poor
      immunogenicity is likely to preclude protection against measles. CD46 is a
      ubiquitously expressed specific receptor for vaccine strains of measles virus.
      CD46 polymorphisms have not been functionally investigated but may affect CD46
      protein expression, which in turn may mediate primary measles antibody responses
      in infants. In a cohort of children aged 12 to 14 months from Perth, Australia (n
      = 137), after their first dose of measles-mumps-rubella (MMR) vaccine, CD46
      polymorphisms were genotyped, and postvaccination measles IgG and CD46 protein
      expression before and after measles lysate stimulation of cells were measured.
      Three CD46 variants (rs7144, rs11118580, and rs2724384) were significantly
      associated with measles virus-specific IgG levels (P = 0.008, P = 0.026, and P =
      0.018, respectively). There were significant differences between CD46 rs7144
      genotypes and CD46 protein expression on T cells, as well as the downregulation
      of CD46 and T-cell frequency after measles lysate stimulation. We show that CD46
      polymorphisms were associated with primary measles antibody responses in naive
      infants. We also report the first association of a measles virus receptor
      polymorphism with functional effects on the receptor, suggesting a possible
      mechanism through which antibody responses are altered. Elucidating all of the
      interconnecting genetic factors that alter primary measles vaccine responses may
      be important for identifying children at risk of poor immunogenicity or vaccine
      failure and for the future design of vaccine strategies to help these children.

PMID- 22357651
TI  - Transcutaneous immunization with a Vibrio cholerae O1 Ogawa synthetic
      hexasaccharide conjugate following oral whole-cell cholera vaccination boosts
      vibriocidal responses and induces protective immunity in mice.
AB  - A shortcoming of currently available oral cholera vaccines is their induction of
      relatively short-term protection against cholera compared to that afforded by
      wild-type disease. We were interested in whether transcutaneous or subcutaneous
      boosting using a neoglycoconjugate vaccine made from a synthetic terminal
      hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa)
      coupled to bovine serum albumin as a carrier (CHO-BSA) could boost
      lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result
      in protective immunity following oral priming immunization with whole-cell
      cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative
      cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral
      priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in
      significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01)
      responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05)
      vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced
      by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses
      following use of CT or LT as an adjuvant were comparable. In a neonatal mouse
      challenge assay, immune serum from boosted mice was associated with 79%
      protective efficacy against death. Our results suggest that transcutaneous and
      subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination
      may be an effective strategy to prolong protective immune responses against V.
      cholerae.

PMID- 22357653
TI  - Neurodegenerative phenotypes in an A53T alpha-synuclein transgenic mouse model
      are independent of LRRK2.
AB  - Mutations in the genes encoding LRRK2 and alpha-synuclein cause autosomal
      dominant forms of familial Parkinson's disease (PD). Fibrillar forms of alpha
      synuclein are a major component of Lewy bodies, the intracytoplasmic
      proteinaceous inclusions that are a pathological hallmark of idiopathic and
      certain familial forms of PD. LRRK2 mutations cause late-onset familial PD with a
      clinical, neurochemical and, for the most part, neuropathological phenotype that
      is indistinguishable from idiopathic PD. Importantly, alpha-synuclein-positive
      Lewy bodies are the most common pathology identified in the brains of PD subjects
      harboring LRRK2 mutations. These observations may suggest that LRRK2 functions in
      a common pathway with alpha-synuclein to regulate its aggregation. To explore the
      potential pathophysiological interaction between LRRK2 and alpha-synuclein in
      vivo, we modulated LRRK2 expression in a well-established human A53T alpha
      synuclein transgenic mouse model with transgene expression driven by the
      hindbrain-selective prion protein promoter. Deletion of LRRK2 or overexpression
      of human G2019S-LRRK2 has minimal impact on the lethal neurodegenerative
      phenotype that develops in A53T alpha-synuclein transgenic mice, including
      premature lethality, pre-symptomatic behavioral deficits and human alpha
      synuclein or glial neuropathology. We also find that endogenous or human LRRK2
      and A53T alpha-synuclein do not interact together to influence the number of
      nigrostriatal dopaminergic neurons. Taken together, our data suggest that alpha
      synuclein-related pathology, which occurs predominantly in the hindbrain of this
      A53T alpha-synuclein mouse model, occurs largely independently from LRRK2
      expression. These observations fail to provide support for a pathophysiological
      interaction of LRRK2 and alpha-synuclein in vivo, at least within neurons of the
      mouse hindbrain.

PMID- 22357654
TI  - Increased mitochondrial biogenesis in muscle improves aging phenotypes in the
      mtDNA mutator mouse.
AB  - Aging is an intricate process that increases susceptibility to sarcopenia and
      cardiovascular diseases. The accumulation of mitochondrial DNA (mtDNA) mutations
      is believed to contribute to mitochondrial dysfunction, potentially shortening
      lifespan. The mtDNA mutator mouse, a mouse model with a proofreading-deficient
      mtDNA polymerase gamma, was shown to develop a premature aging phenotype,
      including sarcopenia, cardiomyopathy and decreased lifespan. This phenotype was
      associated with an accumulation of mtDNA mutations and mitochondrial dysfunction.
      We found that increased expression of peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha), a crucial regulator of mitochondrial
      biogenesis and function, in the muscle of mutator mice increased mitochondrial
      biogenesis and function and also improved the skeletal muscle and heart
      phenotypes of the mice. Deep sequencing analysis of their mtDNA showed that the
      increased mitochondrial biogenesis did not reduce the accumulation of mtDNA
      mutations but rather caused a small increase. These results indicate that
      increased muscle PGC-1alpha expression is able to improve some premature aging
      phenotypes in the mutator mice without reverting the accumulation of mtDNA
      mutations.

PMID- 22357655
TI  - Suppression of alpha-synuclein toxicity and vesicle trafficking defects by
      phosphorylation at S129 in yeast depends on genetic context.
AB  - The aggregation of alpha-synuclein (alphaSyn) is a neuropathologic hallmark of
      Parkinson's disease and other synucleinopathies. In Lewy bodies, alphaSyn is
      extensively phosphorylated, predominantly at serine 129 (S129). Recent studies in
      yeast have shown that, at toxic levels, alphaSyn disrupts Rab homeostasis,
      causing an initial endoplasmic reticulum-to-Golgi block that precedes a
      generalized trafficking collapse. However, whether alphaSyn phosphorylation
      modulates trafficking defects has not been evaluated. Here, we show that
      constitutive expression of alphaSyn in yeast impairs late-exocytic, early
      endocytic and/or recycling trafficking. Although members of the casein kinase I
      (CKI) family phosphorylate alphaSyn at S129, they attenuate alphaSyn toxicity and
      trafficking defects by an S129 phosphorylation-independent mechanism.
      Surprisingly, phosphorylation of S129 modulates alphaSyn toxicity and trafficking
      defects in a manner strictly determined by genetic background. Abnormal endosome
      morphology, increased levels of the endosome marker Rab5 and co-localization of
      mammalian CKI with alphaSyn aggregates are observed in brain sections from
      alphaSyn-overexpressing mice and human synucleinopathies. Our results contribute
      to evidence that suggests alphaSyn-induced defects in endocytosis, exocytosis
      and/or recycling of vesicles involved in these cellular processes might
      contribute to the pathogenesis of synucleinopathies.

PMID- 22357657
TI  - Dissection of a circulating and intrahepatic CD4(+)Foxp3(+) T-cell subpopulation
      in chronic hepatitis B virus (HBV) infection: a highly informative strategy for
      distinguishing chronic HBV infection states.
AB  - BACKGROUND: The definition of CD4(+)Foxp3(+) regulatory T cells (Tregs) is
      challenging as it relates to chronic hepatitis B virus (HBV) infection. Recently,
      the heterogeneity of human CD4(+)Foxp3(+) T cells has been confirmed. METHODS:
      Three circulating CD4(+)Foxp3(+) T-cell subpopulations in chronic HBV patients
      were identified, and their frequencies associated with clinical parameters were
      analyzed. Antigen specificity of Tregs was further studied. RESULTS: We found
      that circulating and intrahepatic CD4(+)CD45RA(-)Foxp3(hi)-activated Tregs
      (aTregs) were selectively increased in patients with chronic active hepatitis B
      and acute-on-chronic liver failure (ACLF) but not in asymptomatic carriers. The
      aTreg frequency was strongly correlated with HBV DNA load but not liver damage.
      In both peripheral blood mononuclear cells and livers, ACLF patients showed a
      dramatically elevated frequency of interleukin 17A-secreting CD45RA(-)Foxp3(lo)
      nonsuppressive T cells (non-Tregs), which were shown to be associated with severe
      liver damage. Interestingly, an HBV core antigen (HBcAg)-derived peptide could
      preferentially expand CD4(+)CD25(+)Foxp3(+) T cells and aTregs in HLA-DR9(+)
      chronic active hepatitis B patients, and these Tregs required ligand-specific
      reactivation for suppressor function. CONCLUSIONS: The delineation of a
      CD4(+)Foxp3(+) T-cell subpopulation is a highly informative strategy for
      distinguishing different chronic HBV infection states. HBcAg-derived peptides may
      be responsible for activation of Tregs that, in turn, specifically inhibit anti
      HBV immune response but not liver inflammation.

PMID- 22357656
TI  - Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during
      eye development.
AB  - Tissue fusion is an essential morphogenetic mechanism in development, playing a
      fundamental role in developing neural tube, palate and the optic fissure.
      Disruption of genes associated with the tissue fusion can lead to congenital
      malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For
      instance, the Pax2 transcription factor is required for optic fissure closure,
      although the mechanism of Pax2 action leading to tissue fusion remains elusive.
      This lack of information defining how transcription factors drive tissue
      morphogenesis at the cellular level is hampering new treatments options. Through
      loss- and gain-of-function analysis, we now establish that pax2 in combination
      with vax2 directly regulate the fas-associated death domain (fadd) gene. In the
      presence of fadd, cell proliferation is restricted in the developing eye through
      a caspase-dependent pathway. However, the loss of fadd results in a proliferation
      defect and concomitant activation of the necroptosis pathway through RIP1/RIP3
      activity, leading to an abnormal open fissure. Inhibition of RIP1 with the small
      molecule drug necrostatin-1 rescues the pax2 eye fusion defect, thereby
      overcoming the underlying genetic defect. Thus, fadd has an essential
      physiological function in protecting the developing optic fissure neuroepithelium
      from RIP3-dependent necroptosis. This study demonstrates the molecular
      hierarchies that regulate a cellular switch between proliferation and the
      apoptotic and necroptotic cell death pathways, which in combination drive tissue
      morphogenesis. Furthermore, our data suggest that future therapeutic strategies
      may be based on small molecule drugs that can bypass the gene defects causing
      common congenital tissue fusion defects.

PMID- 22357658
TI  - Secretome of human bronchial epithelial cells in response to the fungal pathogen
      Aspergillus fumigatus analyzed by differential in-gel electrophoresis.
AB  - BACKGROUND: For years, the analysis of innate responses to the major mold
      pathogen Aspergillus fumigatus has been restricted to specialized cells, such as
      professional phagocytes. More recently, the contribution of the airway epithelial
      barrier has been assessed and studies have shown that it was able to sense and
      react to the Aspergillus infection, for example, by producing cytokines. METHODS:
      To further explore the reaction of the respiratory epithelium to the fungus, we
      analyzed the proteome response of a human bronchial epithelial cell line to
      Aspergillus infection using difference gel electrophoresis. We studied the
      protein pattern of BEAS-2B cell culture supernatant after interaction of the
      cells with Aspergillus during a 15-hour coculture. RESULTS: We found formerly
      unknown aspects of bronchial cell behavior during Aspergillus infection:
      bronchial cells are able to develop both cellular defense mechanisms (ie,
      thioredoxin system activation) and immune reactions (ie, lysosomal degranulation
      and cathepsin activation) in response to the fungal aggression. CONCLUSIONS:
      Bronchial epithelial cells appear to be a more important effector of antifungal
      defense than expected. Degranulation of lysosomal enzymes that might be
      responsible for both fungal growth inhibition and host cell damage suggests that
      inductors/inhibitors of these pathways may be potential targets of therapeutic
      intervention.

PMID- 22357659
TI  - Polymorphisms in the gene that encodes the iron transport protein ferroportin 1
      influence susceptibility to tuberculosis.
AB  - BACKGROUND: We studied the association between iron intake and polymorphisms in
      the iron transporter gene SLC40A1 and the risk of tuberculosis. METHODS: We
      compared iron intake, the frequency of SLC40A1 mutations, and interactions among
      these variables among 98 tuberculosis patients and 125 controls in Kwazulu-Natal,
      South Africa. RESULTS: Four SLC40A1 single-nucleotide polymorphisms (SNPs) were
      associated with an increased risk of tuberculosis and 1 SNP with reduced risk. We
      also found a gene-environment interaction for 4 nonexonic SNPs and iron intake.
      CONCLUSIONS: This pilot study demonstrated an association between polymorphisms
      in SLC40A1 and tuberculosis and provided evidence of an interaction between
      dietary iron and SLC40A1.

PMID- 22357660
TI  - Ribavirin regulates hepatitis C virus replication through enhancing interferon
      stimulated genes and interleukin 8.
AB  - BACKGROUND: The manner in which ribavirin (RBV) enhances the antiviral effects of
      interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated
      whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro. METHODS:
      We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from
      patients with HCV infection who were receiving IFN-alpha therapy with or without
      RBV. We added RBV and/or IFN-alpha to a plasmid-based HCV replication system
      containing a full-length HCV genotype 1a sequence in HepG2 and Huh7 cell lines
      and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of
      ISGs and autocrine IFN-beta. RESULTS: The expression of protein kinase R and
      myxovirus resistance A mRNA was enhanced more with IFN-alpha and RBV than by IFN
      alpha alone in assays in vivo and in vitro. Such enhancement depended on
      autocrine IFN-beta being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in
      the absence of IFN-alpha. The IL-8 upregulation induced by RBV was responsible
      for the activation of activator protein 1 (AP-1). CONCLUSIONS: Ribavirin augments
      the anti-HCV effects of IFN-alpha induced by ISGs through enhancing autocrine IFN
      beta. Moreover, RBV can enhance IL-8 through activating AP-1. Improved
      understanding of ISG modulation by RBV would help to establish a means of
      eliminating HCV.

PMID- 22357661
TI  - Platelets enhance biofilm formation and resistance of endocarditis-inducing
      streptococci on the injured heart valve.
AB  - Infective endocarditis is a typical biofilm-associated infectious disease
      frequently caused by commensal streptococci, but the contribution of host factors
      in biofilm formation is unclear. We found that platelets are essential for in
      vitro biofilm formation by Streptococcus mutans or Streptococcus gordonii grown
      in human plasma. The biofilms were composed of bacterial floes embedded with
      platelet aggregates in layers, and a similar architecture was also detected in
      situ on the injured valves of a rat model of experimental endocarditis. Similar
      to planktonic cells, the streptococci in biofilms were also able to induce
      platelet aggregation, which facilitates multilayer biofilm formation. Entrapping
      of platelets directly enhances the resistance of streptococcal biofilms to
      clindamycin. Prophylactic antibiotics or aspirin can reduce but not prevent or
      abolish biofilm formation on injured heart valves. Therefore, the platelet is a
      host factor for commensal streptococci in the circulation to consolidate biofilm
      formation and protect bacteria against antibiotics.

PMID- 22357662
TI  - Intravenous ferric carboxymaltose accelerates erythropoietic recovery from
      experimental malarial anemia.
AB  - Iron restriction has been proposed as a cause of erythropoietic suppression in
      malarial anemia; however, the role of iron in malaria remains controversial,
      because it may increase parasitemia. To investigate the role of iron-restricted
      erythropoiesis, A/J mice were infected with Plasmodium chabaudi AS, treated with
      intravenous ferric carboxymaltose at different times, and compared with untreated
      controls. Iron treatment significantly increased weight and hemoglobin nadirs and
      provided enhanced reticulocytosis and faster recovery, compared with controls.
      Our findings challenge the restrictive use of iron therapy in malaria and show
      the need for trials of intravenous ferric carboxymaltose as an adjunctive
      treatment for severe malarial anemia.

PMID- 22357664
TI  - Diversity of GABAergic interneurons in layer VIa and VIb of mouse barrel cortex.
AB  - Neocortical layer VI modulates the thalamocortical transfer of information and
      has a significant impact on sensory processing. This function implicates local
      gamma-aminobutyric acidergic (GABAergic) interneurons that have only been partly
      described at the present time. Here, we characterized 85 layer VI GABAergic
      interneurons in acute slices of mouse somatosensory barrel cortex, using whole
      cell current-clamp recordings, single-cell reverse transcription-polymerase chain
      reaction, and biocytin labeling followed by Neurolucida reconstructions.
      Unsupervised clustering based on electrophysiological molecular and morphological
      properties disclosed 4 types of interneurons. The 2 major classes were fast
      spiking cells transcribing parvalbumin (PV) (51%) and adapting interneurons
      transcribing somatostatin (SOM) (26%). The third population (18%) transcribed
      neuropeptide Y (NPY) and appeared very similar to neurogliaform cells. The last
      class (5%) was constituted by well-segregated GABAergic interneurons transcribing
      vasoactive intestinal peptide (VIP). Using transgenic mice expressing GFP under
      the control of the glutamic acid decarboxylase 67k (GAD67) promoter, we
      investigated the densities of GABAergic cells immunolabeled against PV, SOM, VIP,
      and NPY through the depth of layer VI. This analysis revealed that PV and NPY
      translating interneurons concentrate in the upper and lower parts of layer VI,
      respectively. This study provides an extensive characterization of the properties
      of layer VI interneurons.

PMID- 22357663
TI  - Characterization of acute HIV-1 infection in high-risk Nigerian populations.
AB  - BACKGROUND: Acute phase of human immunodeficiency virus (HIV) infection (AHI) may
      account for a significant proportion of HIV-1 transmission. We identified and
      characterized individuals in Nigeria with AHI. METHODS: Individuals were tested
      using a combination of rapid HIV testing in mobile units and laboratory-based
      specimen pooling for nucleic acid amplification testing. Genome sequences were
      characterized. A linear segmented regression model was fit to serial viral load
      (VL) measurements to characterize early VL profiles. RESULTS: Sixteen AHIs were
      identified from 28 655 persons screened. Specimens were genotyped: 7 (43.8%) were
      CRF02_AG, 6 (37.5%) were subtype G, 1 (6.3%) was CRF06_cpx, and 2 (12.5%) were
      unique recombinant forms. No antiretroviral resistance mutations were detected.
      The mean duration of high VL burden from peak to nadir was 76 days (95%
      confidence interval [CI], 58-93 days), and the mean rate of viremic control was 
      0.66 log(10) VL per month. The mean VL at set-point was 4.5 log(10) copies/mL
      (95% CI, 3.9-5.1 log(10) copies/mL). CONCLUSIONS: This study is the first to
      characterize AHI among Nigerians identified as HIV infected before seroconversion
      who would be otherwise missed by conventional HIV testing. Infections by HIV
      subtypes in Nigeria exhibit long periods of high viral burden, which can
      contribute to increased transmissibility.

PMID- 22357665
TI  - Distinct roles of medial and lateral entorhinal cortex in spatial cognition.
AB  - It is known that the entorhinal cortex plays a crucial role in spatial cognition
      in rodents. Neuroanatomical and electrophysiological data suggest that there is a
      functional distinction between 2 subregions within the entorhinal cortex, the
      medial entorhinal cortex (MEC), and the lateral entorhinal cortex (LEC). Rats
      with MEC or LEC lesions were trained in 2 navigation tasks requiring allothetic
      (water maze task) or idiothetic (path integration) information processing and 2
      object exploration tasks allowing testing of spatial and nonspatial processing of
      intramaze objects. MEC lesions mildly affected place navigation in the water maze
      and produced a path integration deficit. They also altered the processing of
      spatial information in both exploration tasks while sparing the processing of
      nonspatial information. LEC lesions did not affect navigation abilities in both
      the water maze and the path integration tasks. They altered spatial and
      nonspatial processing in the object exploration task but not in the one-trial
      recognition task. Overall, these results indicate that the MEC is important for
      spatial processing and path integration. The LEC has some influence on both
      spatial and nonspatial processes, suggesting that the 2 kinds of information
      interact at the level of the EC.

PMID- 22357667
TI  - 99 not out and looking good: the Art of Australasian Psychiatry.

PMID- 22357668
TI  - Psychiatric gadfly: in search of Reginald Ellery.
AB  - OBJECTIVE: To explore the life and contributions of Reginald Spencer Ellery (1897
      1955), one of the most eminent psychiatrists in Australia between the wars.
      CONCLUSIONS: Ellery pioneered malariotherapy and psychoanalysis, mixed with
      leading intellectuals, including Max Harris, John and Sunday Reed, was a member
      of the Communist Party, wrote poetry and published widely on a wide range of
      topics. Ellery was talented, innovative, driven and highly energetic, managing a
      range of activities aside from his work without difficulty. While his writing
      talent was questioned by some, there is no doubting his influence on painters
      such as Albert Tucker and Sidney Nolan and his standing in the intellectual life
      of Melbourne. Ellery was uncompromising in his public stand on issues such as
      communism and psychoanalysis, but by the end of his life he was deeply
      disillusioned. Ellery's autobiography, The Cow Jumped Over the Moon, confirms the
      impression of a restless and creative mind reluctant to be constrained by
      conventional orthodoxy, the most eminent Australian psychiatrist of his time. His
      diverse achievements and talent, now largely forgotten, deserve recognition from
      a profession that is rapidly losing its links with the historical past.

PMID- 22357666
TI  - Lapatinib and obatoclax kill tumor cells through blockade of ERBB1/3/4 and
      through inhibition of BCL-XL and MCL-1.
AB  - Prior studies in breast cancer cells have shown that lapatinib and obatoclax
      interact in a greater than additive fashion to cause cell death and do so through
      a toxic form of autophagy. The present studies sought to extend our analyses to
      the central nervous system (CNS) tumor cells and to further define mechanisms of
      drug action. Lapatinib and obatoclax killed multiple CNS tumor isolates. Cells
      lacking PTEN (phosphatase and tensin homolog on chromosome 10) function were
      relatively resistant to drug combination lethality; expression of PTEN in PTEN
      null cells restored drug sensitivity, and knockdown of PTEN promoted drug
      resistance. On the basis of knockdown of ERBB1-4 (erythroblastic leukemia viral
      oncogene homolog 1-4), we discovered that the inhibition of ERBB1/3/4 receptors
      were most important for enhancing obatoclax lethality rather than ERBB2. In
      parallel, we noted in CNS tumor cells that knockdown of BCL-xL (B-cell lymphoma
      extra large)and MCL-1 (myeloid cell leukemia-1) interacted in an additive fashion
      to facilitate lapatinib lethality. Pretreatment of tumor cells with obatoclax
      enhanced the lethality of lapatinib to a greater extent than concomitant
      treatment. Treatment of animals carrying orthotopic CNS tumor isolates with
      lapatinib- and obatoclax-prolonged survival. Altogether, our data show that
      lapatinib and obatoclax therapy could be of use in the treatment of tumors
      located in the CNS.

PMID- 22357669
TI  - Cause for caution: culture, sensitivity and the World Mental Health Survey
      Initiative.
AB  - OBJECTIVE: This paper examines the cultural grounding and sensitivity in the
      concept, implementation, instrumentation and findings of the World Health
      Organization World Mental Health Survey Initiative (WHO-WMS). CONCLUSIONS: The
      WHO-WMS Initiative is managed by agencies in Boston and Geneva and covers 28
      sites in 27 nations worldwide. It uses the Composite International Diagnostic
      Instrument (CIDI) translated to make diagnoses in 150,000 people. A large body of
      potentially influential data has been produced. The Initiative assumes that
      psychopathology is universal and not culturally determined. This assumption
      cannot be safely sustained. As a result, survey findings using ethnocentrically
      Western instruments and diagnoses may be uninterpretable, yet may misdirect
      policy and treatment. There are cautions here for ethnically and linguistically
      diverse nations such as Australia and New Zealand.

PMID- 22357670
TI  - An examination of Maori tamariki (child) and taiohi (adolescent) traumatic brain
      injury within a global cultural context.
AB  - OBJECTIVE: This paper provides a pragmatic review of the literature to describe
      the size and shape of Maori tamariki (child) and taiohi (adolescent) traumatic
      brain injury (TBI) and highlight issues pertinent to psychiatrists. A review of
      the literature describing cultural aspects of international TBI research further
      contextualises these findings. METHODOLOGY: Literature searches using the words
      indigenous, ethnic, culture, native, native American, native Alaskan, native
      Hawaiian, Maori, aboriginal, traumatic brain injury, rehabilitation, paediatric,
      disparities and epidemiology were undertaken. Reference lists were also examined.
      RESULTS: The literature is adult-centric and selected papers are summarised.
      Significant gaps in the literature were found. Recent local epidemiological
      studies describe Maori tamariki and taiohi as being significantly over
      represented in TBI populations, with poorer outcomes including higher mortality
      rates. International research shows evidence of 'minority' culture being a risk
      factor for certain causes of injury and a differential rehabilitation service
      response. CONCLUSIONS: These findings are important for psychiatrists working
      with Maori. They underscore the importance of asking effectively about possible
      TBI history. Implications for future research to address literature gaps are
      evident. Kaupapa Maori rangahau (research) could be used to explore application
      of tikanga Maori (cultural lore) in prevention, rehabilitation and psychiatric
      management.

PMID- 22357671
TI  - Pathways to practice: overseas trained psychiatrists' experiences of the
      processes involved in commencing professional practice in Australasia.
AB  - OBJECTIVE: There are significant shortages in the psychiatric workforce in
      Australasia, particularly in the rural and remote regions of Australia and New
      Zealand. In response to these shortages, mental health services have recruited
      large numbers of overseas trained psychiatrists (OTP). These are specialist
      psychiatrists, trained and recognised as such in other countries. Our objective
      was to ascertain how OTPs experience the processes of commencing professional
      practice in Australasia. METHOD: OTPs were surveyed to identify the pathways to
      obtaining specialist registration and College Fellowship in Australasia and to
      explore their experiences as they engaged in this process. RESULTS: Although
      limited by a low response rate, the data does highlight a level of discontentment
      among those OTPs surveyed. The key issues identified related to the examination
      process, poor communication between different agencies (including the RANZCP),
      visa and residency related issues, medical board registration difficulties and
      notable differences between Australia and New Zealand. CONCLUSION: There is a
      negative perception among OTPs regarding the existing pathways to registration as
      specialist psychiatrists and the attainment of Fellowship. We submit that the
      RANZCP has a central and important role in resolving some of the underlying
      issues and supporting OTPs as vital and valued members of the workforce in
      Australia and New Zealand.

PMID- 22357672
TI  - The emperor's edicts stop at the village gate.
AB  - OBJECTIVE: To present an overview of policy implementation, and develop
      principles for effective policy development and implementation. METHOD: An
      overview of literature on policy implementation, and analysis of lessons from
      some recent experiences in Australian and New Zealand mental health services.
      CONCLUSIONS: Effective development and deployment of policy is much more complex
      than the commonly held, simplistic compliance model. There are principles that
      can guide effective policy development and implementation. Future areas of study
      include the policy implementation systems and change management processes in the
      health service setting.

PMID- 22357673
TI  - Establishing sensory-based approaches in mental health inpatient care: a
      multidisciplinary approach.
AB  - OBJECTIVE: To reflect upon the implementation of sensory-based approaches within
      the environment of a psychiatric inpatient unit. METHOD: A literature review on
      sensory modulation within psychiatric inpatient care, including seclusion and
      restraint reduction initiatives, was conducted. A variety of sensory-based
      principles were planned, developed and implemented over a 3-year period.
      Preliminary data regarding sensory room use and acute arousal ratings within the
      high-dependency area were analysed. RESULTS: Preliminary sensory room data showed
      a significant reduction in patient distress levels, as per consumer and clinician
      ratings, and that the majority of sensory room sessions were conducted by nursing
      staff. A significant reduction was also found for acute arousal ratings, pre to
      post, for the HDU engagement program. Several issues were uncovered throughout
      implementation of the sensory-based strategies. CONCLUSIONS: Findings indicate
      the importance of cultural change, compared with simply an environmental change,
      giving all staff and consumers the confidence to utilise a variety of sensory
      based methods during times of need. Further Australian research is required to
      explore the positive contribution sensory modulation can potentially make across
      the spectrum of psychiatric settings.

PMID- 22357674
TI  - Are psychiatric Crisis Assessment and Treatment team clinicians on the
      psychotherapy front line?
AB  - OBJECTIVE: There is limited data on the psychological interventions used by
      Crisis Assessment and Treatment (CAT) team clinicians, even though practice
      guidelines stipulate part of their role to be the provision of counselling. This
      study aimed to catalogue and categorise the range of psychotherapeutic
      interventions utilised by clinicians of a CAT team operating within a
      metropolitan area. METHODS: Self-report, episode of care data was collected
      regarding clinicians' views of the type of psychotherapeutic intervention they
      employed and details of what they discussed with patients, and location and
      duration of interventions. RESULTS: Thirty-two care episodes were catalogued. On
      average, clinicians spent 74% of their total contact time with patients engaged
      in psychological interventions. A wide range of strategies, drawn from a broad
      theoretical base, was used. Aside from general approaches aiding engagement,
      interventions could be classified into the following categories: meta-strategy
      ('treatment about the treatment'), 'critical', 'practical', specific
      psychotherapeutic (cognitive-behavioural therapy (CBT) and others), and
      supportive. CONCLUSIONS: Clinicians saw themselves as spending the majority of
      patient contact time engaged in psychological interventions drawn from a broad
      theoretical base. Observational studies of what clinicians actually do and
      empirical investigation of the efficacy thereof may have implications for
      clinician training and supervision.

PMID- 22357675
TI  - Survivors of self-inflicted stab wounds.
AB  - OBJECTIVE: There are a number of studies describing the survivors of self-incised
      wounds, but few studies have described the psychiatric condition of survivors of
      self-inflicted stab wounds. We aimed to describe the characteristics of a
      complete series of patients treated for self-inflicted stab wounds in a major
      hospital, and to compare the characteristics of patients with psychotic illness
      to those with other conditions. METHODS: A review of the files of all patients
      who had a psychiatric evaluation after presenting for treatment following
      deliberate self-harm. Stab wounds were defined as wounds made by a sharp
      instrument in which the width was less than the depth. RESULTS: There were 41
      survivors of self-inflicted stab wounds among 2119 patients assessed after
      deliberate self-harm. Of these, 15 were diagnosed with a psychotic illness and
      the remainder had other conditions, including depression, personality disorder
      and substance use disorder. There was little difference in the demographic
      features, clinical variables and in the proportion who were intoxicated between
      patients diagnosed with psychotic illness and those with other disorders. The
      patients with psychosis were more likely to have inflicted multiple stab wounds,
      to have stabbed their chest or abdomen and to have reported the intention of
      committing suicide. CONCLUSIONS: The results suggest that a significant
      proportion of patients who present for treatment after stabbing themselves suffer
      from a psychotic illness. However, there were few differences in the
      characteristics of the patients who had a diagnosis of psychosis and those with
      other disorders.

PMID- 22357676
TI  - Examining the utility of the Black Dog Institute's online Mood Assessment Program
      in clinical practice.
AB  - OBJECTIVE: To examine qualitatively the usefulness of the Mood Assessment Program
      (MAP) 12 months after an online version for patients was made available for
      access by Australian health practitioners. METHOD: The MAP requires all those
      completing it to provide their observations on its ease of completion. In mid
      2011, we also initiated a satisfaction study among current MAP referrers, with
      responses received from professionals (psychologists, general practitioners,
      psychiatrists and social workers). RESULTS: Feedback from nearly 10,000 patients
      indicated that the great majority judged the MAP as straightforward to complete.
      Only 9% of professionals surveyed offered judgments about the utility of the MAP
      and we capture their judgments. CONCLUSION: Responses supported the acceptability
      of the MAP by patients and its utility to clinicians in relation to diagnostic
      and formulation issues, as well as in advancing communication between
      practitioners and their patients. In addition, the MAP has been shown to improve
      efficiency and time management in assessing those with a mood disorder.

PMID- 22357677
TI  - Building capacity in identification and management of mood disorders: an
      Australia-Sri Lanka collaboration.
AB  - OBJECTIVE: This paper describes a collaborative capacity-building project in the
      identification and management of mood disorders, involving the Black Dog
      Institute in Sydney, Australia, and several organizations in Sri Lanka, and
      presents the qualitative evaluation findings. METHOD: The two-year project
      comprised an initial intensive educational program delivered at the Institute
      with follow-up via email and an online forum (Phase 1), and continuing
      collaboration with the eight Sri Lankan clinicians and their respective
      organizations to build awareness of mood disorders and train others in Sri Lanka
      (Phase 2). RESULTS: The eight trainees planned and executed several joint and
      separate activities during Phase 2, with an emphasis on raising awareness of mood
      disorders and health professional training. Evaluations of the local training
      activities were very positive. CONCLUSIONS: The collaborative, systematic and
      systemic approach, and the train-the-trainer model adopted, has worked well. This
      project has built capacity in mood disorders among mental health clinicians in
      Sri Lanka, including those working in primary care. It has contributed to the
      implementation of national mental health policy, strengthened local networks and
      established new connections with Australian institutions. 'North-south'
      collaborations such as this would make good investments for international bodies
      and development agencies.

PMID- 22357678
TI  - The life and music of Alexander Scriabin: megalomania revisited.
AB  - OBJECTIVE: To shed more light on the relationship between the grandiosity of the
      Russian composer Alexander Scriabin (1872-1915) and his creative output, and
      discuss its implications for psychopathology. CONCLUSIONS: Scriabin was a highly
      original composer, who brought innovations to the idiom of music. He firmly
      believed that music and philosophy were inseparable and that music was only a
      vehicle for expressing ideas and emotional states. As Scriabin was getting more
      preoccupied with mysticism and as he was developing a belief that his mission was
      to save the world through his art, his music became more esoteric. Over the last
      five years of his life, he composed relatively little, as he was working on a
      supergrandiose project that he never completed. Scriabin's grandiosity, which had
      delusional qualities, might have diminished his creativity towards the end of his
      life and contributed to his destructive fantasies. All along, his social facade
      was well preserved and he was not noted to exhibit overt psychotic behaviour,
      suggesting an encapsulated delusional megalomania. The implications of
      megalomania, especially in creative or otherwise influential individuals, are
      briefly discussed.

PMID- 22357679
TI  - What psychiatrists should know about sporadic Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: To provide psychiatrists with relevant, up to date information about
      sporadic Creutzfeldt-Jakob disease. CONCLUSIONS: A 59-year-old bookkeeper
      presented with psychiatric symptoms in the context of stressors and past history
      of depression, for which her GP prescribed sertraline and olanzapine. Following a
      further deterioration in her mental state she was referred to acute psychiatric
      services, and there found to have dementia and myoclonus, and investigations
      supported a diagnosis of probable Creutzfeldt-Jakob disease, sporadic type
      (sCJD). This paper serves to outline the emerging literature challenging the
      notion that suggests psychiatric symptoms are uncommon in the presentation of
      sCJD.

PMID- 22357680
TI  - Cognitive deficits in Indigenous patients with psychosis.

PMID- 22357681
TI  - The suicide of Adam Czerniakow.

PMID- 22357682
TI  - Drug company push polling?

PMID- 22357683
TI  - Use of mental health outcome measures in clinical practice.

PMID- 22357684
TI  - Trainees' wishes and experience of psychotherapy training: a binational survey.

PMID- 22357685
TI  - From the President.

PMID- 22357686
TI  - From the Honorary Secretary.

PMID- 22357695
TI  - Cell-free DNA as a biomarker in the context of cancer, viruses, and methylation.

PMID- 22357696
TI  - CpG methylation as a tool to characterize cell-free Kaposi sarcoma herpesvirus
      DNA.
AB  - We studied the presence of Kaposi sarcoma herpesvirus sequences in cell-free DNA
      (cfDNA) isolated from the blood of patients with AIDS-related Kaposi sarcoma (KS)
      and primary effusion lymphoma (PEL). The use of paramagnetic beads linked to
      methyl-CpG binding domain protein allowed separation of virion and cell-derived
      DNA. Only virion DNA was detected in the blood of KS patients, whereas cell
      derived DNA was detected in a patient with AIDS-related PEL. The difference in
      the origins of cfDNA in these settings may in part reflect very different
      proliferative indices in KS and PEL tumor tissue.

PMID- 22357697
TI  - Exploring the factor structure of implicit and explicit cognitions associated
      with depression.
AB  - Dual-process models of cognitive vulnerability to depression propose that
      implicit (automatic) and explicit (effortful) processes are involved in
      depression. The current study investigated the underlying structure of four
      implicit and four explicit cognitive biases associated with depression in an
      undergraduate sample (N = 355). An exploratory principal-axis factor analysis of
      implicit and explicit measures of self-esteem, dysfunctional beliefs, and memory
      for positive and negative stimuli produced a three-factor solution that was
      inconsistent with the dual process (two factor) account. Subsequent confirmatory
      factor analyses of biases exhibited by a hold-out sample also failed to support
      the hypothesized dual-process model and supported a three-factor solution.
      Overall, the results indicate that the latent structure of measures investigated
      in this study is not characterized by a clear differentiation between implicit
      and explicit cognition and that alternative models and measurement strategies
      should be investigated. 

PMID- 22357698
TI  - Improving personality facet scores with multidimensional computer adaptive
      testing: an illustration with the NEO PI-R.
AB  - Narrowly defined personality facet scores are commonly reported and used for
      making decisions in clinical and organizational settings. Although these facets
      are typically related, scoring is usually carried out for a single facet at a
      time. This method can be ineffective and time consuming when personality tests
      contain many highly correlated facets. This article investigates the possibility
      of increasing the precision of the NEO PI-R facet scores by scoring items with
      multidimensional item response theory and by efficiently administering and
      scoring items with multidimensional computer adaptive testing (MCAT). The
      increase in the precision of personality facet scores is obtained from exploiting
      the correlations between the facets. Results indicate that the NEO PI-R could be
      substantially shorter without attenuating precision when the MCAT methodology is
      used. Furthermore, the study shows that the MCAT methodology is particularly
      appropriate for constructs that have many highly correlated facets.

PMID- 22357699
TI  - The risk of cancer in people with diabetes and chronic kidney disease.
AB  - BACKGROUND: Diabetes and chronic kidney disease (CKD) are both associated with an
      increased risk of cancer but it is unclear whether diabetes complicated by CKD
      further augments an individual's cancer risk. The aim of our study was to
      determine the association of CKD [defined as an estimated glomerular filtration
      rate (eGFR) < 60 mL/min] with the overall and site-specific risks of incident
      cancers among individuals with Type 2 diabetes. METHODS: Cox proportional hazard
      regression models and competing risk analyses were used to examine the univariate
      and multivariate adjusted associations between reduced kidney function and the
      overall and site-specific risks of cancer in participants enrolled in the Action
      in Diabetes and Vascular disease: Preterax and Diamicron MR controlled evaluation
      (ADVANCE) trial. RESULTS: Over a median follow-up of 5.0 years, 700 malignant
      neoplasms occurred in the 11 140 (6.4%) participants. There was no increase in
      overall cancer risk [adjusted hazard ratio: 1.07 (95% confidence interval: 0.89
      1.29, P = 0.50)] or site-specific cancer risk for individuals with CKD (defined
      as eGFR < 60 mL/min) compared to those without CKD at baseline. These results
      were robust to multiple methods and thresholds used to estimate CKD. CONCLUSIONS:
      Mild to moderate CKD does not increase the risk of cancer in people with Type 2
      diabetes. ADVANCE is registered with ClincalTrial.gov (number NCT00145925).

PMID- 22357700
TI  - Optimizing the dialysate calcium concentration in bicarbonate haemodialysis.
AB  - BACKGROUND: There is no consensus regarding the optimal dialysate calcium
      concentration (DCa) during haemodialysis (HD). Low DCa may predispose to acute
      arrhythmias, whereas high DCa increases the long-term risk of soft tissue
      calcifications. METHODS: Twenty-two HD patients treated in four dialysis centres
      underwent two HD sessions, respectively, with 1.5 and 1.25 mmol/L total DCa.
      Calcium mass balance (CMB) was calculated from ionized calcium (iCa) in the
      dialysate and blood at the start and end of each run, using a kinetic formula to
      define the mean concentrations in the blood and dialysate and then estimating
      CMBs over the entire treatments. RESULTS: Mean blood iCa levels increased using
      1.5 DCa, whereas they remained unchanged using 1.25 DCa. Diffusive CMB positively
      correlated with the dialysate/blood iCa gradient. With 1.5 DCa, diffusive CMBs
      were strongly positive at the blood side and negative at the dialysate side,
      indicating transfer from dialysate to blood. With 1.25 DCa, despite a negative
      dialysate/blood iCa gradient, diffusive CMB was slightly positive in blood and
      negative in dialysate. The global balances based on both the convective and
      diffusive components showed a positive net transfer of Ca from dialysate to blood
      with 1.5 DCa and an approximately neutral Ca flux with 1.25 DCa. CONCLUSIONS:
      While CMB is nearly neutral when using 1.25 DCa, the use of 1.5 DCa results in a
      gain of Ca during HD. The risks associated with Ca load should be considered in
      the choice of DCa prescription for HD but need also be weighed against the risk
      of worse haemodynamic dialysis tolerance.

PMID- 22357701
TI  - Typhoid Fever and the challenge of nonmalaria febrile illness in sub-saharan
      Africa.

PMID- 22357702
TI  - Multidrug-resistant typhoid fever with neurologic findings on the Malawi
      Mozambique border.
AB  - BACKGROUND: Salmonella enterica serovar Typhi causes an estimated 22 million
      cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an
      outbreak of unexplained febrile illnesses with neurologic findings, determined to
      be typhoid fever, along the Malawi-Mozambique border. METHODS: The investigation
      included active surveillance, interviews, examinations of ill and convalescent
      persons, medical chart reviews, and laboratory testing. Classification as a
      suspected case required fever and >=1 other finding (eg, headache or abdominal
      pain); a probable case required fever and a positive rapid immunoglobulin M
      antibody test for typhoid (TUBEX TF); a confirmed case required isolation of
      Salmonella Typhi from blood or stool. Isolates underwent antimicrobial
      susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE).
      RESULTS: We identified 303 cases from 18 villages with onset during March
      November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases.
      Forty patients presented with focal neurologic abnormalities, including a
      constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and
      parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant
      to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also
      resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by
      PFGE. CONCLUSIONS: The unusual neurologic manifestations posed a diagnostic
      challenge that was resolved through rapid typhoid antibody testing in the field
      and subsequent blood culture confirmation in the Malawi national reference
      laboratory. Extending laboratory diagnostic capacity, including blood culture, to
      populations at risk for typhoid fever in Africa will improve outbreak detection,
      response, and clinical treatment.

PMID- 22357703
TI  - A large outbreak of typhoid fever associated with a high rate of intestinal
      perforation in Kasese District, Uganda, 2008-2009.
AB  - BACKGROUND: Salmonella enterica serovar Typhi (Salmonella Typhi) causes an
      estimated 22 million typhoid fever cases and 216 000 deaths annually worldwide.
      In Africa, the lack of laboratory diagnostic capacity limits the ability to
      recognize endemic typhoid fever and to detect outbreaks. We report a large
      laboratory-confirmed outbreak of typhoid fever in Uganda with a high proportion
      of intestinal perforations (IPs). METHODS: A suspected case of typhoid fever was
      defined as fever and abdominal pain in a person with either vomiting, diarrhea,
      constipation, headache, weakness, arthralgia, poor response to antimalarial
      medications, or IP. From March 4, 2009 to April 17, 2009, specimens for blood and
      stool cultures and serology were collected from suspected cases. Antimicrobial
      susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed
      on Salmonella Typhi isolates. Surgical specimens from patients with IP were
      examined. A community survey was conducted to characterize the extent of the
      outbreak. RESULTS: From December 27, 2007 to July 30, 2009, 577 cases, 289
      hospitalizations, 249 IPs, and 47 deaths from typhoid fever occurred; Salmonella
      Typhi was isolated from 27 (33%) of 81 patients. Isolates demonstrated multiple
      PFGE patterns and uniform susceptibility to ciprofloxacin. Surgical specimens
      from 30 patients were consistent with typhoid fever. Estimated typhoid fever
      incidence in the community survey was 8092 cases per 100 000 persons.
      CONCLUSIONS: This typhoid fever outbreak was detected because of an elevated
      number of IPs. Underreporting of milder illnesses and delayed and inadequate
      antimicrobial treatment contributed to the high perforation rate. Enhancing
      laboratory capacity for detection is critical to improving typhoid fever control.

PMID- 22357704
TI  - Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids
      in mice.
AB  - Postnatal intestinal ontogenesis in an animal model of diabesity may recapitulate
      morphological and transduction features of diabesity-induced intestinal dysplasia
      and its amelioration by endogenous (n-3) polyunsaturated fatty acids (PUFA).
      Proliferation, differentiation, and transduction aspects of intestinal
      ontogenesis have been studied here in obese, insulin-resistant db/db mice, in fat
      1 transgene coding for desaturation of (n-6) PUFA into (n-3) PUFA, in db/db
      crossed with fat-1 mice, and in control mice. Diabesity resulted in increased
      colonic proliferation and dedifferentiation of epithelial colonocytes and goblet
      cells, with increased colonic beta-catenin and hepatocyte nuclear factor (HNF)
      4alpha transcriptional activities accompanied by enrichment in HNF-4alpha-bound
      (n-6) PUFA. In contrast, in fat-1 mice, colonic proliferation was restrained,
      accompanied by differentiation of crypt stem cells into epithelial colonocytes
      and goblet cells and by decrease in colonic beta-catenin and HNF-4alpha
      transcriptional activities, with concomitant enrichment in HNF-4alpha-bound (n-3)
      PUFA at the expense of (n-6) PUFA. Colonic proliferation and differentiation, the
      profile of beta-catenin and HNF-4alpha-responsive genes, and the composition of
      HNF-4alpha-bound PUFA of db/db mice reverted to wild-type by introducing the fat
      1 gene into the db/db context. Suppression of intestinal HNF-4alpha activity by
      (n-3) PUFA may ameliorate diabesity-induced intestinal ontogenesis and offer an
      effective preventive modality for colorectal cancer.

PMID- 22357705
TI  - NR2F1 disrupts synergistic activation of the MTTP gene transcription by HNF
      4alpha and HNF-1alpha.
AB  - Regulation of microsomal triglyceride transfer protein (MTP) expression mainly
      occurs at the transcriptional level. We have previously shown that MTTP gene
      expression was repressed in nondifferentiated intestinal cells by nuclear
      receptor 2 family 1 (NR2F1). However, mechanisms involved in the repression of
      MTP by NR2F1 were not elucidated. Here, we show that MTP expression requires
      hepatic nuclear factor (HNF)-4alpha transcription factor. Different HNF-1
      proteins synergistically enhance MTP promoter activity along with HNF-4alpha by
      binding to different cis elements. NR2F1 does not alter individual effects of HNF
      4alpha and HNF-1 proteins on the MTTP gene promoter. However, NR2F1 suppresses
      synergistic activation of the MTP promoter by HNF-4alpha/HNF-1alpha by binding to
      a direct repeat 1 (DR1) element. This suppression is further enhanced in the
      presence of nuclear receptor corepressor 1. In short, these studies identified a
      novel mechanism of MTP repression that involves binding of NR2F1 to the DR1
      element and recruitment of corepressors. In this mechanism, NR2F1 does not affect
      activities of individual transcription factors; instead, it abrogates synergistic
      activation by HNF-4alpha and HNF-1 proteins.

PMID- 22357706
TI  - The N-terminal region of acyl-CoA synthetase 3 is essential for both the
      localization on lipid droplets and the function in fatty acid uptake.
AB  - Cytosolic lipid droplets (LDs) are storage organelles for neutral lipids derived
      from endogenous metabolism. Acyl-CoA synthetase family proteins are essential
      enzymes in this biosynthetic pathway, contributing activated fatty acids.
      Fluorescence microscopy showed that ACSL3 is localized to the endoplasmic
      reticulum (ER) and LDs, with the distribution dependent on the cell type and the
      supply of fatty acids. The N-terminus of ACSL3 was necessary and sufficient for
      targeting reporter proteins correctly, as demonstrated by subcellular
      fractionation and confocal microscopy. The N-terminal region of ACSL3 was also
      found to be functionally required for the enzyme activity. Selective
      permeabilization and in silico analysis suggest that ACSL3 assumes a hairpin
      membrane topology, with the N-terminal hydrophobic amino acids forming an
      amphipathic helix restricted to the cytosolic leaflet of the ER membrane. ACSL3
      was effectively translocated from the ER to nascent LDs when neutral lipid
      synthesis was stimulated by the external addition of fatty acids. Cellular fatty
      acid uptake was increased by overexpression and reduced by RNA interference of
      ACSL3. In conclusion, the structural organization of ACSL3 allows the fast and
      efficient movement from the ER to emerging LDs. ACSL3 not only esterifies fatty
      acids with CoA but is also involved in the cellular uptake of fatty acids,
      presumably indirectly by metabolic trapping. The unique localization of the acyl
      CoA synthetase ACSL3 on LDs suggests a function in the local synthesis of lipids.

PMID- 22357708
TI  - When I's meet: sharing subjective experience with someone from the outgroup.
AB  - Believing one shares a subjective experience with another (i.e., I-sharing)
      fosters connections among strangers and alters perceptions of the ingroup and
      outgroup. In this article, the authors ask whether I-sharing also fosters liking
      for members of a salient outgroup. Study 1 establishes that I-sharing promotes
      liking for the other sex, even among people with salient social identities. Study
      2 shows that I-sharing promotes liking for a member of the sexual orientation
      outgroup, whether it occurs before or after group memberships get revealed. Study
      3 focuses on salient race categories and looks at the effects of I-sharing versus
      value-sharing as a function of shared group membership. For those high in
      existential isolation, I-sharing trumps value-sharing, regardless of the I
      sharer's social identity. I-sharing may offer a way of improving attitudes toward
      outgroup members that still enables people to embrace their differing social
      identities.

PMID- 22357707
TI  - APOL1 allelic variants are associated with lower age of dialysis initiation and
      thereby increased dialysis vintage in African and Hispanic Americans with non
      diabetic end-stage kidney disease.
AB  - BACKGROUND: The APOL1 G1 and G2 genetic variants make a major contribution to the
      African ancestry risk for a number of common forms of non-diabetic end-stage
      kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants
      with age of dialysis initiation and dialysis vintage (defined by the time between
      dialysis initiation and sample collection) in African and Hispanic Americans,
      diabetic and non-diabetic ESKD. METHODS: We examined APOL1 genotypes in 995
      African and Hispanic American dialysis patients with diabetic and non-diabetic
      ESKD. RESULTS: The mean age of dialysis initiation for non-diabetic African
      American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier
      than those without APOL1 risk alleles (t-test, P=0.0003). Similar results were
      found in the non-diabetic Hispanic American cohort, but not in the diabetic
      cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation
      (t-test, P=0.0452), but G2 heterozygotes did not show such an effect. At the age
      of 70, 92% of individuals with two APOL1 risk alleles had already initiated
      dialysis, compared with 76% of the patients without APOL1 risk alleles. Although
      two APOL1 risk alleles are also associated with ~2 years increased in dialysis
      vintage, further analysis showed that this increase is fully explained by earlier
      age of dialysis initiation. CONCLUSIONS: Two APOL1 risk alleles significantly
      predict lower age of dialysis initiation and thereby increased dialysis vintage
      in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A
      single APOL1 G1, but not G2, risk allele also lowers the age of dialysis
      initiation, apparently consistent with gain of injury or loss of function
      mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease
      that manifests at younger ages in African ancestry populations.

PMID- 22357709
TI  - Twin and sibling attachment in a nationally representative sample.
AB  - The objective of this research was to evaluate the hypothesis that twin
      relationships are attachments, using data from a nationally representative
      sample. The results indicated that twin siblings were more likely than nontwin
      siblings to be attached to their siblings. Moreover, analyses indicated that both
      attachment theoretical and inclusive fitness perspectives are necessary for
      explaining these findings. Namely, twins were more likely to be attached than
      nontwin siblings, as expected from an attachment perspective. But identical twins
      were more likely than fraternal twins to be attached to one another, as might be
      expected from an inclusive fitness perspective. Cross-sectional analyses
      indicated that older people are less likely than younger people to use their
      sibling as an attachment figure compared to younger people and that married
      adults are less likely to use their sibling as an attachment figure than
      nonmarried people.

PMID- 22357710
TI  - A comparison of power analysis methods for evaluating effects of a predictor on
      slopes in longitudinal designs with missing data.
AB  - In many longitudinal studies, evaluating the effect of a binary or continuous
      predictor variable on the rate of change of the outcome, i.e. slope, is often of
      primary interest. Sample size determination of these studies, however, is
      complicated by the expectation that missing data will occur due to missed visits,
      early drop out, and staggered entry. Despite the availability of methods for
      assessing power in longitudinal studies with missing data, the impact on power of
      the magnitude and distribution of missing data in the study population remain
      poorly understood. As a result, simple but erroneous alterations of the sample
      size formulae for complete/balanced data are commonly applied. These 'naive'
      approaches include the average sum of squares and average number of subjects
      methods. The goal of this article is to explore in greater detail the effect of
      missing data on study power and compare the performance of naive sample size
      methods to a correct maximum likelihood-based method using both mathematical and
      simulation-based approaches. Two different longitudinal aging studies are used to
      illustrate the methods. 

PMID- 22357711
TI  - The meaning of insulin to Hispanic immigrants with type 2 diabetes and their
      families.
AB  - PURPOSE: The purpose of this study was to explore the meaning of insulin among a
      sample of Hispanic immigrants with type 2 diabetes and their family
      members/significant others. METHOD: Forty-three Hispanics with type 2 diabetes
      and their family members/significant others were recruited in the southeastern
      United States for a family-based intervention study on diabetes self-management.
      Focus groups were conducted in which participants with diabetes and family
      members were asked to describe their perceptions of insulin. The sessions were
      audiotaped and transcribed, translated from Spanish into English, and analyzed
      using standard content analysis. This article reports the findings as well as
      demographic information and hemoglobin A1C levels of participants. RESULTS: The
      meaning of insulin was described by both Hispanic immigrants with type 2 diabetes
      and their family members/significant others. Participants' perceptions were
      categorized into three major themes: (1) negative perceptions of insulin therapy,
      (2) perceived barriers to insulin therapy, and (3) positive experiences with
      insulin emerged from qualitative data. CONCLUSIONS: The Hispanic immigrants with
      diabetes and their family members/significant others in this study described
      perceptions and fears of insulin indicating a lack of understanding of the
      diabetes disease process and the progressive nature of diabetes. Strategies and
      further research are necessary to dispel negative perceptions and facilitate
      positive experiences with insulin for patients and family members/significant
      others.

PMID- 22357712
TI  - Stroke incidence in older US Hispanics: is foreign birth protective?
AB  - BACKGROUND AND PURPOSE: Although Hispanics are the fastest growing ethnic group
      in the United States, relatively little is known about stroke risk in US
      Hispanics. We compare stroke incidence and socioeconomic predictors in US- and
      foreign-born Hispanics with patterns among non-Hispanic whites. METHODS: Health
      and Retirement Study participants aged 50+ years free of stroke in 1998 (mean
      baseline age, 66.3 years) were followed through 2008 for self- or proxy-reported
      first stroke (n=15 784; 1388 events). We used discrete-time survival analysis to
      compare stroke incidence among US-born (including those who immigrated before age
      7 years) and foreign-born Hispanics with incidence in non-Hispanic whites. We
      also examined childhood and adult socioeconomic characteristics as predictors of
      stroke among Hispanics, comparing effect estimates with those for non-Hispanic
      whites. RESULTS: In age- and sex-adjusted models, US-born Hispanics had higher
      odds of stroke onset than non-Hispanic whites (OR, 1.44; 95% CI, 1.08-1.90), but
      these differences were attenuated and nonsignificant in models that controlled
      for childhood and adulthood socioeconomic factors (OR, 1.07; 95% CI, 0.80-1.42).
      In contrast, in models adjusted for all demographic and socioeconomic factors,
      foreign-born Hispanics had significantly lower stroke risk than non-Hispanic
      whites (OR, 0.58; 95% CI, 0.41-0.81). The impact of socioeconomic predictors on
      stroke did not differ between Hispanics and whites. CONCLUSIONS: In this
      longitudinal national cohort, foreign-born Hispanics had lower incidence of
      stroke incidence than non-Hispanic whites and US-born Hispanics. Findings suggest
      that foreign-born Hispanics may have a risk factor profile that protects them
      from stroke as compared with other Americans.

PMID- 22357713
TI  - Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C
      Dijon Study.
AB  - OBJECTIVE: The relation between inflammation and brain MRI findings in the
      elderly remains poorly known. We investigated the association of circulating
      interleukin-6 (IL-6) and C-reactive protein (CRP) levels with baseline and
      longitudinal white matter hyperintensities (WMH), silent brain infarction, and
      brain volumes in community-dwelling elderly free of dementia. METHODS: We
      included 1,841 participants aged 65 to 80 years from the Three City-Dijon cohort.
      Participants followed an MRI examination at baseline and after a 4-year follow-up
      (n = 1,316). IL-6 and CRP concentrations were measured at baseline from fasting
      blood samples. WMH were detected with an automatic imaging processing method and
      gray matter, hippocampal, white matter, and CSF volumes were estimated with voxel
      based morphometry. Silent brain infarctions were assessed visually and defined as
      focal lesions of >=3 mm in the absence of stroke. We used analysis of covariance
      and logistic regression to model the associations between inflammatory biomarkers
      and brain MRI findings adjusting for potential confounders. RESULTS: In cross
      sectional analyses, higher IL-6 levels were associated with higher WMH volumes (p
      < 0.01), lower gray matter (p = 0.001) and hippocampal (p = 0.01) volumes, and
      increasing CSF volumes (p = 0.002) in a dose-relationship pattern. Similar but
      weaker relations were observed for CRP. We observed no associations between
      baseline inflammatory biomarker levels and the evolution of MRI findings over 4
      years. CONCLUSIONS: IL-6, and, to a lesser degree, CRP levels were associated
      with WMH severity as well as global markers of brain atrophy. These results
      suggest that an inflammatory process may be involved in both age-associated brain
      alterations.

PMID- 22357714
TI  - Autosomal dominant tauopathy with parkinsonism and central hypoventilation.

PMID- 22357715
TI  - Lamotrigine and side effects: another headache.

PMID- 22357716
TI  - Autonomic dysfunction in chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - OBJECTIVES: Autonomic deficits in chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite
      Autonomic Severity Score (CASS) is a validated instrument for laboratory
      quantitation of autonomic failure derived from standard autonomic reflex tests.
      We characterized dysautonomia in CIDP using CASS. METHODS: Autonomic function was
      retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0
      (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3),
      cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic
      deficits was measured with Neuropathy Impairment Score (NIS). Degree of small
      fiber involvement was assessed with quantitative sensation testing.
      Thermoregulatory sweat test (TST) was available in 8 patients. RESULTS: Patients
      (25 men) were middle-aged (45.0 +/- 14.9 years) with longstanding CIDP (3.5 +/-
      4.3 years) of moderate severity (NIS, 46.5 +/- 32.7). Autonomic symptoms were
      uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%).
      Autonomic deficits (CASS >=1) were frequent (22/47; 47%) but very mild (CASS, 0.8
      +/- 0.9; CASS <=3, all cases). Deficits were predominantly sudomotor (16/47; 34%)
      and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was
      abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was
      predominantly distal and postganglionic. Somatic deficits (disease duration,
      severity, small fiber deficits) did not predict presence of autonomic deficits.
      CONCLUSION: Our data characterize the autonomic involvement in classic CIDP as
      mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at
      the distal postganglionic axon. Extensive or severe autonomic involvement (CASS
      >=4) in suspected CIDP should raise concern for an alternative diagnosis.

PMID- 22357717
TI  - CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease.
AB  - OBJECTIVE: Measures of neuronal damage/dysfunction are likely good surrogates for
      disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may
      offer utility in predicting disease progression and guiding prognostic and
      outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has
      demonstrated potential utility as a marker of neuronal injury. We here
      investigate the utility of VILIP-1 and VILIP-1/Abeta42 in predicting rates of
      cognitive decline in early AD. METHODS: Individuals with a clinical diagnosis of
      very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p
      tau181, and Abeta42 were followed longitudinally for an average of 2.6 years.
      Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes
      (CDR-SB), and global composite scores. Mixed linear models assessed the ability
      of CSF biomarker measures to predict rates of cognitive decline over time.
      RESULTS: Baseline CSF VILIP-1 and VILIP-1/Abeta42 levels predicted rates of
      future decline in CDR-SB and global composite scores over the follow-up period.
      Individuals with CSF VILIP-1 >=560 pg/mL (corresponding to the upper tercile)
      progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global
      scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85
      boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF
      tau, p-tau181, tau/Abeta42, and p-tau181/Abeta42 also predicted more rapid
      cognitive decline in CDR-SB and global scores over time. CONCLUSION: These
      findings suggest that CSF VILIP-1 and VILIP-1/Abeta42 predict rates of global
      cognitive decline similarly to tau and tau/Abeta42, and may be useful CSF
      surrogates for neurodegeneration in early AD.

PMID- 22357718
TI  - Lamotrigine and aseptic meningitis.
AB  - OBJECTIVE: The purpose of this case series is to characterize a recently
      identified association of the antiepileptic drug (AED) lamotrigine with aseptic
      meningitis based on cases reported to the Food and Drug Administration (FDA)'s
      Adverse Event Reporting System (AERS) database. METHODS: We performed a data
      mining analysis of 9 AEDs from the FDA's AERS database. We applied the multi-item
      gamma Poisson shrinker (MGPS) algorithm to the entire AERS database through
      November 2, 2009, to generate empirical Bayes geometric mean (EBGM) values with
      corresponding confidence intervals for 9 AEDs and the adverse event code
      "meningitis aseptic." The AERS database was also searched for postmarketing
      reports of aseptic meningitis associated with lamotrigine and a detailed review
      of each case was performed. RESULTS: Forty AERS cases were identified in this
      review. Findings from the AERS reports revealed CSF profiles with features of
      both bacterial as well as viral meningitis. Fifteen cases documented a positive
      rechallenge; the median time to onset of symptoms upon rechallenge was only 60
      minutes. Data mining analysis of several anticonvulsants resulted in
      disproportionate reporting solely for lamotrigine. CONCLUSION: There appears to
      be an association between lamotrigine use and aseptic meningitis. It is notable
      that nearly 40% of cases in this case series reported a positive rechallenge.
      Lamotrigine-associated aseptic meningitis should be considered in the
      differential diagnosis of culture-negative meningitis. This case series
      highlights the need for continued pharmacovigilance and the importance of
      systematic monitoring of patients treated with antiepileptic medications.

PMID- 22357719
TI  - Neural correlates of disturbed perception of verticality.
AB  - OBJECTIVE: Perception of verticality can be perturbed after cortical stroke.
      However, a relationship between lesion location and pathologic perception of
      verticality is still a matter of debate since previous studies revealed
      contradictory results. Thus, the aim of the current study was to test whether
      specific cortical lesions were associated with tilts of subjective visual
      vertical (SVV) and to determine the critical brain areas that cause such tilts in
      the case of a lesion. METHODS: SVV was systematically studied in 54 patients (22
      patients with left-sided and 32 patients with right-sided lesions) with acute
      unilateral strokes, analyzed by modern voxel-wise lesion-behavior mapping
      techniques. RESULTS: The data give evidence for an association between tilt of
      SVV and the insular cortex (IC) and inferior frontal gyrus (IFG) in both
      hemispheres. Whereas the IC seems to be the prominent structure in the left
      hemisphere, the IFG is most affected in the right hemisphere. Furthermore, other
      cortical regions such as the superior temporal gyrus (STG) and the rolandic
      operculum as well as-subcortically-the inferior occipitofrontal fascicle and the
      superior longitudinal fascicle seem to be involved in the vestibulo-cortical
      network for the perception of verticality in the roll plane. CONCLUSION: Damage
      to these regions might lead to an imbalance within the vestibular network of one
      hemisphere due to a deficit in multimodal signal processing.

PMID- 22357720
TI  - Central nervous system involvement in dengue: a study in fatal cases from a
      dengue endemic area.
AB  - OBJECTIVE: This study aimed to determine the frequency of CNS infection by dengue
      virus (DENV) in individuals with fatal outcomes. METHODS: Samples of 150
      individuals suspect of an infection disease and with fatal outcomes were
      investigated for evidence of the presence of DENV. The sampling was made up of
      150 CSF, 120 tissue samples, and 109 blood specimens. The tests used were viral
      isolation, reverse transcriptase PCR, immunohistochemistry, nonstructural 1
      antigen, and immunoglobulin M detection. RESULTS: Out of 150 studied patients, 84
      were dengue positive. Evidence of the presence of DENV was found in 41 CSF,
      showing the following neurologic diagnosis: 46.3% encephalitis, 34.1%
      meningoencephalitis, and 19.5% meningitis, giving a frequency of 48.8% of the 84
      dengue-positive cases. The major clinical manifestations observed on these
      individuals were fever, headache, mental irritability, breathless, vomiting,
      muscle pain, tiredness, abdominal pain, somnolence, restlessness, dizziness,
      cough, seizure, coma, and neck stiffness. CONCLUSION: Clinical manifestations and
      laboratory-positive results in CSF that may indicate the presence of DENV led to
      consider the invasion of CNS by DENV in these fatal cases studied, and showed
      that neurologic pathology was an important fatal complication in dengue cases.

PMID- 22357721
TI  - Predictors of maternal and child double burden of malnutrition in rural Indonesia
      and Bangladesh.
AB  - BACKGROUND: Many developing countries now face the double burden of malnutrition,
      defined as the coexistence of a stunted child and overweight mother within the
      same household. OBJECTIVE: This study sought to estimate the prevalence of the
      double burden of malnutrition and to identify associated maternal, child, and
      household characteristics in rural Indonesia and Bangladesh. DESIGN: A total of
      247,126 rural households that participated in the Indonesia Nutrition
      Surveillance System (2000-2003) and 168,317 rural households in the Bangladesh
      Nutritional Surveillance Project (2003-2006) were included in the analysis.
      Maternal and child double burden (MCDB) and its association with individual and
      household characteristics were determined by using logistic regression models.
      RESULTS: MCDB was observed in 11% and 4% of the households in rural Indonesia and
      Bangladesh, respectively. Maternal short stature [Indonesia (OR: 2.32; 95% CI:
      2.25, 2.40); Bangladesh (OR: 2.11; 95% CI: 1.96, 2.26)], and older age were
      strong predictors of MCDB. Child characteristics such as older age and being
      female were associated with an increased odds of MCDB, whereas currently being
      breastfed was protective against MCDB [Indonesia (OR: 0.84; 95% CI: 0.81, 0.84);
      Bangladesh (OR: 0.55; 95% CI: 0.52, 0.58)]. A large family size and higher weekly
      per capita household expenditure predicted MCDB [Indonesia (OR: 1.34; 95% CI:
      1.28, 1.40); Bangladesh (OR: 1.94; 95% CI: 1.77, 2.12)]. CONCLUSIONS: Double
      burden is not exclusive to urban areas. Future policies and interventions should
      address under- and overweight simultaneously in both rural and urban developing
      country settings.

PMID- 22357722
TI  - Sleep restriction leads to increased activation of brain regions sensitive to
      food stimuli.
AB  - BACKGROUND: Epidemiologic evidence shows an increase in obesity concurrent with a
      reduction in average sleep duration among Americans. Although clinical studies
      propose that restricted sleep affects hormones related to appetite, neuronal
      activity in response to food stimuli after restricted and habitual sleep has not
      been investigated. OBJECTIVE: The objective of this study was to determine the
      effects of partial sleep restriction on neuronal activation in response to food
      stimuli. DESIGN: Thirty healthy, normal-weight [BMI (in kg/m2): 22-26] men and
      women were recruited (26 completed) to participate in a 2-phase inpatient
      crossover study in which they spent either 4 h/night (restricted sleep) or 9
      h/night (habitual sleep) in bed. Each phase lasted 6 d, and functional magnetic
      resonance imaging was performed in the fasted state on day 6. RESULTS: Overall
      neuronal activity in response to food stimuli was greater after restricted sleep
      than after habitual sleep. In addition, a relative increase in brain activity in
      areas associated with reward, including the putamen, nucleus accumbens, thalamus,
      insula, and prefrontal cortex in response to food stimuli, was observed.
      CONCLUSION: The findings of this study link restricted sleep and susceptibility
      to food stimuli and are consistent with the notion that reduced sleep may lead to
      greater propensity to overeat.

PMID- 22357723
TI  - Dietary flavonoid intakes and risk of type 2 diabetes in US men and women.
AB  - BACKGROUND: Data from mechanistic studies support a beneficial effect of specific
      flavonoids on insulin sensitivity. However, few studies have evaluated the
      relation between intakes of different flavonoid subclasses and type 2 diabetes.
      OBJECTIVE: The objective was to evaluate whether dietary intakes of major
      flavonoid subclasses (ie, flavonols, flavones, flavanones, flavan-3-ols, and
      anthocyanins) are associated with the risk of type 2 diabetes in US adults.
      DESIGN: We followed up a total of 70,359 women in the Nurses' Health Study (NHS;
      1984-2008), 89,201 women in the NHS II (1991-2007), and 41,334 men in the Health
      Professionals Follow-Up Study (1986-2006) who were free of diabetes,
      cardiovascular disease, and cancer at baseline. RESULTS: During 3,645,585 person
      years of follow-up, we documented 12,611 incident cases of type 2 diabetes.
      Higher intakes of anthocyanins were significantly associated with a lower risk of
      type 2 diabetes (pooled HR for the 3 cohorts from a comparison of extreme
      quintiles: 0.85; 95% CI: 0.80, 0.91; P-trend < 0.001) after multivariate
      adjustment for age, BMI, and lifestyle and dietary factors. Consumption of
      anthocyanin-rich foods, particularly blueberries (pooled HR: 0.77 from a
      comparison of >=2 servings/wk with <1 serving/mo; 95% CI: 0.68, 0.87; P-trend <
      0.001) and apples/pears (pooled HR: 0.77 from a comparison of >=5 servings/wk
      with <1 serving/mo; 95% CI: 0.65, 0.83; P-trend < 0.001), was also associated
      with a lower risk of type 2 diabetes. No significant associations were found for
      total flavonoid intake or other flavonoid subclasses. CONCLUSION: A higher
      consumption of anthocyanins and anthocyanin-rich fruit was associated with a
      lower risk of type 2 diabetes.

PMID- 22357725
TI  - Protein supplementation lowers blood pressure in overweight adults: effect of
      dietary proteins on blood pressure (PROPRES), a randomized trial.
AB  - BACKGROUND: Dietary protein intake may help to manage blood pressure (BP) and
      prevent complications associated with elevated BP. OBJECTIVE: The objective of
      this study was to determine whether 4 wk of increased protein intake (~25%
      compared with ~15% of energy intake that isoenergetically replaces carbohydrate
      intake) lowers office and daytime BP compared with increased carbohydrate intake.
      DESIGN: A randomized, double-blind, parallel study compared consumption of 3 * 20
      g protein/d (20% pea, 20% soy, 30% egg, and 30% milk-protein isolate) with 3 * 20
      g maltodextrin/d. Protein or maltodextrin were isoenergetically substituted for a
      sugar-sweetened drink. Primary outcomes were office and daytime BP. A total of 99
      men and women [age range: 20-70 y; BMI (in kg/m2): 25-35] with untreated elevated
      BP (BP >=130/85 and <160/100 mm Hg) were randomly assigned. Ninety-four
      completers (51 subjects in the maltodextrin group, 43 subjects in the protein
      group) were included in the analyses. RESULTS: Office systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) were 4.9 +/- 1.7 mm Hg (P = 0.005) and
      2.7 +/- 1.3 mm Hg (P = 0.05) lower, respectively, in the protein group. Daytime
      SBP was 4.6 +/- 1.7 mm Hg lower in the protein group (P = 0.006), whereas daytime
      DBP did not differ between groups (P = 0.37). Urinary sodium excretion was higher
      in the maltodextrin group (P = 0.004). CONCLUSION: Increased protein intake, at
      the expense of maltodextrin, lowers BP in overweight adults with upper-range
      prehypertension and grade 1 hypertension. This trial was registered at
      www.trialregister.nl as NTR 1362.

PMID- 22357724
TI  - Infant regulation of intake: the effect of free glutamate content in infant
      formulas.
AB  - BACKGROUND: We recently discovered that infants randomly assigned to a formula
      high in free amino acids (extensive protein hydrolysate formula; ePHF) during
      infancy consumed less formula to satiation and gained less weight than did
      infants fed an isocaloric formula low in free amino acids (cow milk formula;
      CMF). OBJECTIVE: Because ePHF and CMF differ markedly in concentrations of free
      glutamate, we tested the hypothesis that the higher glutamate concentrations in
      ePHF promote satiation and satiety. DESIGN: In this counterbalanced, within
      subject study, infants <4 mo of age (n = 30) visited our laboratory for 3 sets of
      2 consecutive infant-led formula meals over 3 test days. Infants were fed 1 of 3
      isocaloric formulas during each first meal: CMF, ePHF, or CMF with added free
      glutamate to approximate concentrations in ePHF (CMF+glu). When infants signaled
      hunger again, they were fed a second meal of CMF. From these data, we calculated
      satiety ratios for each of the 3 formulas by dividing the intermeal interval by
      the amount of formula consumed during that particular first meal. RESULTS:
      Infants consumed significantly less CMF+glu (P < 0.02) and ePHF (P < 0.04) than
      CMF during the first meals. They also showed greater levels of satiety after
      consuming CMF+glu or ePHF: satiety ratios for CMF+glu (P < 0.03) and ePHF (P <
      0.05) were significantly higher than for CMF. CONCLUSION: These findings suggest
      a role of free glutamate in infant intake regulation and call into question the
      claim that formula feeding impairs infants' abilities to self regulate energy
      intake.

PMID- 22357726
TI  - Distribution models and a dated phylogeny for Chilean Oxalis species reveal
      occupation of new habitats by different lineages, not rapid adaptive radiation.
AB  - Among the World's most challenging environments for plant life is the Atacama
      Desert, an arid zone extending over 1300 km and from sea level to 2000/3000 m
      altitude along the southwestern Andean foothills. Plants there and in the
      adjacent Mediterranean zone exhibit striking adaptations, and we here address the
      question whether in a species-rich clade such adaptations arose in parallel, at
      different times, or simultaneously. Answering this type of question has been a
      major concern of evolutionary biology over the past few years, with a growing
      consensus that lineages tend to be conservative in their vegetative traits and
      niche requirements. Combined nuclear and chloroplast DNA sequences for 112
      species of Oxalidales (4900 aligned nucleotides) were used for a fossil
      calibrated phylogeny that includes 43 of the 54 species of Chilean Oxalis, and
      species distribution models (SDMs) incorporating precipitation, temperature, and
      fog, and the phylogeny were used to reconstruct ancestral habitat preferences,
      relying on likelihood and Bayesian techniques. Since uneven collecting can reduce
      the power of SDMs, we compared 3 strategies to correct for collecting effort.
      Unexpectedly, the Oxalis flora of Chile consists of 7 distant lineages that
      originated at different times prior to the last Andean uplift pulse; some had
      features preadapting them to seasonally arid or xeric conditions. Models that
      incorporated fog and a "collecting activity surface" performed best and
      identified the Mediterranean zone as a hotspot of Oxalis species as well as
      lineage diversity because it harbors a mix of ancient and young groups, including
      insufficiently arid-adapted species. There is no evidence of rapid adaptive
      radiation.

PMID- 22357727
TI  - MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a
      large model space.
AB  - Since its introduction in 2001, MrBayes has grown in popularity as a software
      package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC)
      methods. With this note, we announce the release of version 3.2, a major upgrade
      to the latest official release presented in 2003. The new version provides
      convergence diagnostics and allows multiple analyses to be run in parallel with
      convergence progress monitored on the fly. The introduction of new proposals and
      automatic optimization of tuning parameters has improved convergence for many
      problems. The new version also sports significantly faster likelihood
      calculations through streaming single-instruction-multiple-data extensions (SSE)
      and support of the BEAGLE library, allowing likelihood calculations to be
      delegated to graphics processing units (GPUs) on compatible hardware. Speedup
      factors range from around 2 with SSE code to more than 50 with BEAGLE for codon
      problems. Checkpointing across all models allows long runs to be completed even
      when an analysis is prematurely terminated. New models include relaxed clocks,
      dating, model averaging across time-reversible substitution models, and support
      for hard, negative, and partial (backbone) tree constraints. Inference of species
      trees from gene trees is supported by full incorporation of the Bayesian
      estimation of species trees (BEST) algorithms. Marginal model likelihoods for
      Bayes factor tests can be estimated accurately across the entire model space
      using the stepping stone method. The new version provides more output options
      than previously, including samples of ancestral states, site rates, site
      d(N)/d(S) rations, branch rates, and node dates. A wide range of statistics on
      tree parameters can also be output for visualization in FigTree and compatible
      software.

PMID- 22357728
TI  - NeXML: rich, extensible, and verifiable representation of comparative data and
      metadata.
AB  - In scientific research, integration and synthesis require a common understanding
      of where data come from, how much they can be trusted, and what they may be used
      for. To make such an understanding computer-accessible requires standards for
      exchanging richly annotated data. The challenges of conveying reusable data are
      particularly acute in regard to evolutionary comparative analysis, which
      comprises an ever-expanding list of data types, methods, research aims, and
      subdisciplines. To facilitate interoperability in evolutionary comparative
      analysis, we present NeXML, an XML standard (inspired by the current standard,
      NEXUS) that supports exchange of richly annotated comparative data. NeXML defines
      syntax for operational taxonomic units, character-state matrices, and
      phylogenetic trees and networks. Documents can be validated unambiguously.
      Importantly, any data element can be annotated, to an arbitrary degree of
      richness, using a system that is both flexible and rigorous. We describe how the
      use of NeXML by the TreeBASE and Phenoscape projects satisfies user needs that
      cannot be satisfied with other available file formats. By relying on XML Schema
      Definition, the design of NeXML facilitates the development and deployment of
      software for processing, transforming, and querying documents. The adoption of
      NeXML for practical use is facilitated by the availability of (1) an online
      manual with code samples and a reference to all defined elements and attributes,
      (2) programming toolkits in most of the languages used commonly in evolutionary
      informatics, and (3) input-output support in several widely used software
      applications. An active, open, community-based development process enables future
      revision and expansion of NeXML.

PMID- 22357729
TI  - Reflections on the 14th World Conference on Lung Cancer: A European Perspective.

PMID- 22357730
TI  - A new era for the systemic therapy of neuroendocrine tumors.
AB  - Carcinoids and pancreatic neuroendocrine tumors are becoming increasingly common,
      with the majority of patients presenting with either lymph node involvement or
      metastatic disease. An improved understanding of the molecular mechanisms
      involved in these tumors has implicated several pathways that have led to new
      therapeutic approaches. In this manuscript, we describe the biology of
      neuroendocrine tumors and approaches to systemic therapy. We review early data
      regarding the use of cytotoxics and several recent studies employing more
      targeted approaches that promise to change the standard of care. Specifically,
      phase III studies indicate that pharmacologic inhibition of the vascular
      endothelial growth factor pathway with sunitinib, and of the mammalian target of
      rapamycin pathway with everolimus, appears to have altered the natural history of
      these diseases. These successes set the stage for further advances in the
      management of patients with neuroendocrine tumors.

PMID- 22357732
TI  - Palliative care consultation service and palliative care unit: why do we need
      both?
AB  - BACKGROUND: Palliative care (PC) infrastructure has developed differently around
      the globe. Whereas some institutions consider the palliative care unit (PCU) a
      valuable component, others report that the sole provision of a state-of-the art
      palliative care consultation service (PCCS) suffices to adequately care for the
      severely ill and dying. OBJECTIVE: To aid institutional planning, this study
      aimed at gathering patient data to distinguish assignments of a concomitantly run
      PCU and PCCS at a large hospital and academic medical center. METHODS:
      Demographics, Eastern Cooperative Oncology Group performance status,
      symptom/problem burden, discharge modality, and team satisfaction with care for
      all 601 PCU and 851 PCCS patients treated in 2009 and 2010 were retrospectively
      analyzed. RESULTS: Patients admitted to the PCU versus those consulted by the
      PCCS: (a) had a significantly worse performance status (odds ratio [OR], 1.48);
      (b) were significantly more likely to suffer from severe symptoms and
      psychosocial problems (OR, 2.05), in particular concerning physical suffering and
      complexity of care; and (c) were significantly much more likely to die during
      hospital stay (OR, 11.03). For patients who were dying or in other challenging
      clinical situations (suffering from various severe symptoms), self-rated team
      satisfaction was significantly higher for the PCU than the PCCS. CONCLUSION: This
      study presents a direct comparison between patients in a PCU and a PCCS. Results
      strongly support the hypothesis that the coexistence of both institutions in one
      hospital contributes to the goal of ensuring optimal high-quality PC for patients
      in complex and challenging clinical situations.

PMID- 22357733
TI  - Genetic ablation of Slc4a10 alters the expression pattern of transporters
      involved in solute movement in the mouse choroid plexus.
AB  - Mutational changes of one transporter can have deleterious effects on epithelial
      function leaving the cells with the options of either compensating for the loss
      of function or dedifferentiating. Previous studies have shown that the choroid
      plexus epithelium (CPE) from mice lacking the Na(+)-dependent Cl(-)/HCO(3)(-)
      exchanger (NCBE) encoded by Slc4a10 leads to retargeting of the Na(+)/H(+)
      exchanger 1 (NHE1) from the luminal to the basolateral plasma membrane. We
      hypothesized that disruption of NCBE, the main basolateral Na(+) importer in the
      CPE, would lead to a compensatory increase in the abundance of other important
      transport proteins in this tissue. Aquaporin-1 (AQP1) abundance was 42.7% lower
      and Na,K-ATPase 36.4% lower in the CPE of Slc4a10 knockout mice, respectively.
      The NHE1 binding ezrin cytoskeleton appeared disrupted in Slc4a10 knockout mice,
      whereas no changes were observed in cellular polarization with respect to claudin
      2 and appearance of luminal surface microvilli. The renal proximal tubule
      constitutes a leaky epithelium with high transport rate similar to CPE. Here,
      Slc4a10 knockout did not affect Na,K-ATPase or AQP1 expression. CPE from AQP1
      knockout mice has a secretory defect similar to Slc4a10 mice. However, neither
      NCBE nor Na,K-ATPase expression was affected in CPE from AQP1 knockout mice. By
      contrast, the abundance of Na,K-ATPase and NBCe1 was decreased by 23 and 31.7%,
      respectively, in AQP1 knockout proximal tubules, while the NHE3 abundance was
      unchanged. In conclusion, CPE lacking NCBE seems to spare the molecular machinery
      involved in CSF secretion rather than compensate for the loss of the Na(+)
      loader. Slc4a10 knockout seems to be more deleterious to CPE than AQP1 knockout.

PMID- 22357731
TI  - A prospective study of the factors shaping antibody responses to the AS03
      adjuvanted influenza A/H1N1 vaccine in cancer outpatients.
AB  - PURPOSE: To identify the determinants of antibody responses to adjuvanted
      influenza A/H1N1/09 vaccines in a cohort of cancer outpatients. PATIENTS AND
      METHODS: Patients with cancer and controls were enrolled in a prospective single
      center field study. Two doses of AS03-adjuvanted pandemic influenza vaccine were
      administered to patients and one dose was administered to controls. Antibody
      responses were measured using hemagglutination inhibition and confirmed by
      microneutralization. Geometric mean titers (GMTs) and seroprotection rates
      (defined as GMTs >=40) were compared. RESULTS: Immunizations were safe and well
      tolerated in 197 cancer patients (lymphoma, 57; glioma, 26; lung or head and
      neck, 37; gastrointestinal, 41; breast, 36) and 138 controls. Similar
      seroprotection rates (82.3% versus 87%) and GMTs (336.9 versus 329.9) were
      achieved after two doses of adjuvanted vaccine in cancer patients and one dose in
      controls. Univariate analyses identified older age, prior immunization against
      seasonal influenza, lymphoma, CD4 count, active chemotherapy, and rituximab and
      steroid treatments as being associated with weaker antibody responses. However,
      only age and chemotherapy plus rituximab remained independent determinants of
      vaccine responses in multivariate analyses. CONCLUSIONS: Two doses of AS03
      adjuvanted influenza vaccine elicited potent antibody responses in most cancer
      patients despite ongoing chemotherapy, with the exception of rituximab-induced B
      cell depletion. Oncology patients treated in an outpatient setting benefit from
      preventive vaccination against influenza with adjuvanted vaccines.

PMID- 22357734
TI  - SGLT and GLUT: are they teammates? Focus on "Mouse SGLT3a generates proton
      activated currents but does not transport sugar".

PMID- 22357735
TI  - Real-time differential labeling of blood, interstitium, and lymphatic and single
      field analysis of vasculature dynamics in vivo.
AB  - Lymph nodes are highly organized structures specialized for efficient regulation
      of adaptive immunity. The blood and lymphatic systems within a lymph node play
      essential roles by providing functionally distinct environments for lymphocyte
      entry and egress, respectively. Direct imaging and measurement of vascular
      microenvironments by intravital multiphoton microscopy provide anatomical and
      mechanistic insights into the essential events of lymphocyte trafficking.
      Lymphocytes, blood endothelial cells, and lymphatic endothelial cells express
      sphingosine 1-phosphate receptor 1, a key G protein-coupled receptor regulating
      cellular egress and a modulator of endothelial permeability. Here we report the
      development of a differential vascular labeling (DVL) technique in which a single
      intravenous injection of a fluorescent dextran, in combination with fluorescent
      semiconductor quantum dot particles, differentially labels multiple blood and
      lymphatic compartments in a manner dependent on the size of the fluorescent
      particle used. Thus DVL allows measurement of endothelial integrity in multiple
      vascular compartments and the affects or pharmacological manipulation in vascular
      integrity. In addition, this technique allows for real-time observation of
      lymphocyte trafficking across physiological barriers differentiated by DVL. Last,
      single-field fluid movement dynamics can be derived, allowing for the
      simultaneous determination of fluid flow rates in diverse blood and lymphatic
      compartments.

PMID- 22357736
TI  - Strain waveform dependence of stress fiber reorientation in cyclically stretched
      osteoblastic cells: effects of viscoelastic compression of stress fibers.
AB  - Actin stress fibers (SFs) of cells cultured on cyclically stretched substrate
      tend to reorient in the direction in which a normal strain of substrate becomes
      zero. However, little is known about the mechanism of this reorientation. Here we
      investigated the effects of cyclic stretch waveform on SF reorientation in
      osteoblastic cells. Cells adhering to silicone membranes were subjected to cyclic
      uniaxial stretch, having one of the following waveforms with an amplitude of 8%
      for 24 h: triangular, trapezoid, bottom hold, or peak hold. SF reorientation of
      these cells was then analyzed. No preferential orientation was observed for the
      triangular and the peak-hold waveforms, whereas SFs aligned mostly in the
      direction with zero normal strain (~55 degrees ) with other waveforms, especially
      the trapezoid waveform, which had a hold time both at loaded and unloaded states.
      Viscoelastic properties of SFs were estimated in a quasi-in situ stress
      relaxation test using intact and SF-disrupted cells that maintained their shape
      on the substrate. The dynamics of tension F(SFs) acting on SFs during cyclic
      stretching were simulated using these properties. The simulation demonstrated
      that F(SFs) decreased gradually during cyclic stretching and exhibited a
      compressive value (F(SFs) < 0). The magnitude and duration time of the
      compressive forces were relatively larger in the group with a trapezoid waveform.
      The frequency of SF orientation had a significant negative correlation with the
      applied compressive forces integrated with time in a strain cycle, and the
      integrated value was largest with the trapezoid waveform. These results may
      indicate that the applied compressive forces on SFs have a significant effect on
      the stretch-induced reorientation of SFs, and that SFs realigned to avoid their
      compression. Stress relaxation of SFs might be facilitated during the holding
      period in the trapezoid waveform, and depolymerization and reorientation of SFs
      were significantly accelerated by their viscoelastic compression.

PMID- 22357737
TI  - Regulation of cell proliferation of human induced pluripotent stem cell-derived
      mesenchymal stem cells via ether-a-go-go 1 (hEAG1) potassium channel.
AB  - The successful generation of a high yield of mesenchymal stem cells (MSCs) from
      human induced pluripotent stem cells (iPSCs) may represent an unlimited cell
      source with superior therapeutic benefits for tissue regeneration to bone marrow
      (BM)-derived MSCs. We investigated whether the differential expression of ion
      channels in iPSC-MSCs was responsible for their higher proliferation capacity
      than BM-MSCs. The expression of ion channels for K(+), Na(+), Ca(2+), and Cl(-)
      was examined by RT-PCR. The electrophysiological properties of iPSC-MSCs and BM
      MSCs were then compared by patch-clamp experiments to verify their functional
      roles. Significant mRNA expression of ion channel genes including KCa1.1, KCa3.1,
      KCNH1, Kir2.1, SCN9A, CACNA1C, and Clcn3 was observed in both human iPSC-MSCs and
      BM-MSCs, whereas Kir2.2 and Kir2.3 were only detected in human iPSC-MSCs. Five
      types of currents [big-conductance Ca(2+)-activated K(+) current (BK(Ca)),
      delayed rectifier K(+) current (IK(DR)), inwardly rectifying K(+) current
      (I(Kir)), Ca(2+)-activated K(+) current (IK(Ca)), and chloride current (I(Cl))]
      were found in iPSC-MSCs (83%, 47%, 11%, 5%, and 4%, respectively) but only four
      of them (BK(Ca), IK(DR), I(Kir), and IK(Ca)) were identified in BM-MSCs (76%,
      25%, 22%, and 11%, respectively). Cell proliferation was examined with MTT or
      bromodeoxyuridine assay, and doubling times were 2.66 and 3.72 days for iPSC-MSCs
      and BM-MSCs, respectively, showing a 1.4-fold discrepancy. Blockade of IK(DR)
      with short hairpin RNA or human ether-a-go-go 1 (hEAG1) channel blockers, 4-AP
      and astemizole, significantly reduced the rate of proliferation of human iPSC
      MSCs. These treatments also decreased the rate of proliferation of human BM-MSCs
      albeit to a lesser extent. These findings demonstrate that the hEAG1 channel
      plays a crucial role in controlling the proliferation rate of human iPSC-MSCs and
      to a lesser extent in BM-MSCs.

PMID- 22357739
TI  - Consumption of vitamin D-and calcium-fortified soft white cheese lowers the
      biochemical marker of bone resorption TRAP 5b in postmenopausal women at moderate
      risk of osteoporosis fracture.
AB  - The prevention of increased bone remodeling in postmenopausal women at low 10-y
      risk of osteoporotic fractures essentially relies on reinforcement of
      environmental factors known to positively influence bone health, among which
      nutrition plays an important role. In institutionalized women in their mid
      eighties, we previously found that consumption of fortified soft plain cheese
      increased vitamin D, calcium, and protein intakes, reduced bone resorption
      biochemical markers, particularly the serum bone specific acid phosphatase
      tartrate resistant acid phosphatase, isoform 5b (TRAP 5b) that reflects
      osteoclast activity, and stimulated the serum bone anabolic factor insulin-like
      growth factor-I (IGF-I). Whether these effects occur in much younger women was
      tested in a prospective control study. Seventy-one healthy postmenopausal women
      aged 56.6 +/- 3.9 y (mean +/- SD) with low spontaneous supply of both Ca and
      vitamin D were randomized to consume daily (treated, n = 36) or not (controls, n
      = 35) two servings (2 * 100 g) of skimmed-milk, soft plain cheese for 6 wk. The
      vitamin D and Ca-fortified dairy product provided daily: 661 kJ, 2.5 MUg vitamin
      D, 400 mg calcium, and 13.8 g protein. At the end of the intervention, the
      decrease in TRAP 5b and the increase in IGF-I were greater in the treated than in
      the control group (P < 0.02). The changes in serum carboxy terminal crosslinked
      telopeptide of type I collagen did not differ significantly between the two
      groups. In conclusion, like in elderly women, consumption by healthy
      postmenopausal women of a vitamin D and calcium-fortified dairy product that also
      increases the protein intake, reduces the serum concentration of the bone
      resorption biomarker TRAP 5b. This response, combined with the increase in serum
      IGF-I, is compatible with a nutrition-induced reduction in postmenopausal bone
      loss rate.

PMID- 22357738
TI  - Differential regulation of a CLC anion channel by SPAK kinase ortholog-mediated
      multisite phosphorylation.
AB  - Shrinkage-induced inhibition of the Caenorhabditis elegans cell volume and cell
      cycle-dependent CLC anion channel CLH-3b occurs by concomitant phosphorylation of
      S742 and S747, which are located on a 175 amino acid linker domain between
      cystathionine-beta-synthase 1 (CBS1) and CBS2. Phosphorylation is mediated by the
      SPAK kinase homolog GCK-3 and is mimicked by substituting serine residues with
      glutamate. Type 1 serine/threonine protein phosphatases mediate swelling-induced
      channel dephosphorylation. S742E/S747E double mutant channels are constitutively
      inactive and cannot be activated by cell swelling. S742E and S747E mutant
      channels were fully active in the absence of GCK-3 and were inactive when
      coexpressed with the kinase. Both channels responded to cell volume changes.
      However, the S747E mutant channel activated and inactivated in response to cell
      swelling and shrinkage, respectively, much more slowly than either wild-type or
      S742E mutant channels. Slower activation and inactivation of S747E was not due to
      altered rates of dephosphorylation or dephosphorylation-dependent conformational
      changes. GCK-3 binds to the 175 amino acid inter-CBS linker domain. Coexpression
      of wild-type CLH-3b and GCK-3 with either wild-type or S742E linkers gave rise to
      similar channel activity and regulation. In contrast, coexpression with the S747E
      linker greatly enhanced basal channel activity and increased the rate of
      shrinkage-induced channel inactivation. Our findings suggest the intriguing
      possibility that the phosphorylation state of S742 in S747E mutant channels
      modulates GCK-3/channel interaction and hence channel phosphorylation. These
      results provide a foundation for further detailed studies of the role of
      multisite phosphorylation in regulating CLH-3b and GCK-3 activity.

PMID- 22357740
TI  - Marginal maternal zinc deficiency in lactating mice reduces secretory capacity
      and alters milk composition.
AB  - Dietary analysis predicts that marginal Zn deficiency is common in women of
      reproductive age. The lack of reliable biomarkers limits the capacity to assess
      Zn status and consequently understand effects of maternal Zn deficiency. We
      determined effects of marginal maternal Zn deficiency on mammary gland function,
      milk secretion, and milk composition in mice. Mice (n = 12/diet) were fed
      marginal (ZD; 15 mg Zn/kg diet) or adequate (ZA; 30 mg Zn/kg diet) Zn diets for
      30 d prior to conception through mid-lactation. Mice fed the ZD had a higher
      plasma Zn concentration (~20%; P < 0.05) but lower milk Zn concentration (~15%; P
      < 0.05) compared with mice fed the ZA. ZnT2 abundance was higher (P < 0.05) in
      mice fed the ZD compared with mice fed the ZA; no effect on ZnT4 abundance was
      detected. The Zn concentration of mammary gland mitochondria tended to be ~40%
      greater in mice fed ZD (P = 0.07); this was associated with apoptosis and lower
      milk secretion (~80%; P < 0.01). Total milk protein was ~25% higher (P < 0.05),
      although the abundance of the major milk proteins (caseins and whey acidic
      protein) was lower (P < 0.05) in mice fed the ZD. Proteomic analysis of milk
      proteins revealed an increase (P < 0.05) in four proteins in mice fed the ZD.
      These findings illustrate that marginal maternal Zn deficiency compromises
      mammary gland function and milk secretion and alters milk composition. This
      suggests that lactating women who consume inadequate Zn may not produce and/or
      secrete an adequate amount of high quality milk to provide optimal nutrition to
      their developing infant.

PMID- 22357741
TI  - Oat beta-glucan and dietary calcium and phosphorus differentially modify
      intestinal expression of proinflammatory cytokines and monocarboxylate
      transporter 1 and cecal morphology in weaned pigs.
AB  - Physiologic effects of dietary oat beta-glucan and low and high dietary calcium
      phosphorus (CaP) on intestinal morphology and gene expression related to SCFA
      absorption, mucus production, inflammation, and peptide digestion have not been
      established in weaned mammals. We therefore randomized 32 weaned pigs into 4
      equal groups that received a cornstarch-casein-based diet with low (65% of the Ca
      and P requirement) and high (125 and 115% of the Ca and P requirement,
      respectively) CaP levels and low- and high-CaP diets supplemented with 8.95% oat
      beta-glucan concentrate for 14 d. High-CaP diets downregulated duodenal
      expression of IL-1beta (P < 0.05) by 30% compared with low-CaP diets.
      Furthermore, high-CaP diets reduced (P < 0.05) cecal crypt depth by 14% compared
      with low-CaP diets. Dietary beta-glucan upregulated the expression of cecal MCT1
      (P < 0.05) by 40% and that of colonic IL-6 (P < 0.05) by 142% compared with the
      control diet. Correlation analysis indicated that cecal MCT1 (r = 0.99, P <
      0.001) and colonic IL-6 (r = 0.84, P < 0.05) expression was positively related to
      luminal butyrate and total SCFA, respectively, indicating that beta-glucan may
      partly modify gene expression via increased SCFA generation. In conclusion, beta
      glucan and CaP levels modulated the expression of selected genes and morphology
      in the postweaning period, but effects were specific to intestinal segment. The
      present results further indicate that, in addition to being essential nutrients
      for bone accretion, dietary CaP level may modify the intestinal tissue response
      in young pigs.

PMID- 22357742
TI  - High-fat and fructose intake induces insulin resistance, dyslipidemia, and liver
      steatosis and alters in vivo macrophage-to-feces reverse cholesterol transport in
      hamsters.
AB  - Reverse cholesterol transport (RCT) promotes the egress of cholesterol from
      peripheral tissues to the liver for biliary and fecal excretion. Although not
      demonstrated in vivo, RCT is thought to be impaired in patients with metabolic
      syndrome, in which liver steatosis prevalence is relatively high. Golden Syrian
      hamsters were fed a nonpurified (CON) diet and normal drinking water or a high
      fat (HF) diet containing 27% fat, 0.5% cholesterol, and 0.25% deoxycholate as
      well as 10% fructose in drinking water for 4 wk. Compared to CON, the HF diet
      induced insulin resistance and dyslipidemia, with significantly higher plasma non
      HDL-cholesterol concentrations and cholesteryl ester transfer protein activity.
      The HF diet induced severe liver steatosis, with significantly higher cholesterol
      and TG levels compared to CON. In vivo RCT was assessed by i.p. injecting 3H
      cholesterol labeled macrophages. Compared to CON, HF hamsters had significantly
      greater 3H-tracer recoveries in plasma, but not HDL. After 72 h, 3H-tracer
      recovery in HF hamsters was 318% higher in liver and 75% lower in bile (P <
      0.01), indicating that the HF diet impaired hepatic cholesterol fluxes. However,
      macrophage-derived cholesterol fecal excretion was 45% higher in HF hamsters than
      in CON hamsters. This effect was not related to intestinal cholesterol
      absorption, which was 89% higher in HF hamsters (P < 0.05), suggesting a possible
      upregulation of transintestinal cholesterol excretion. Our data indicate a
      significant increase in macrophage-derived cholesterol fecal excretion in a
      hamster model of metabolic syndrome, which may not compensate for the diet
      induced dyslipidemia and liver steatosis.

PMID- 22357743
TI  - Fermentable fiber ameliorates fermentable protein-induced changes in microbial
      ecology, but not the mucosal response, in the colon of piglets.
AB  - Dietary inclusion of fermentable carbohydrates (fCHO) is reported to reduce large
      intestinal formation of putatively toxic metabolites derived from fermentable
      proteins (fCP). However, the influence of diets high in fCP concentration on
      epithelial response and interaction with fCHO is still unclear. Thirty-two weaned
      piglets were fed 4 diets in a 2 * 2 factorial design with low fCP/low fCHO [14.5%
      crude protein (CP)/14.5% total dietary fiber (TDF)]; low fCP/high fCHO (14.8%
      CP/16.6% TDF); high fCP low fCHO (19.8% CP/14.5% TDF); and high fCP/high fCHO
      (20.1% CP/18.0% TDF) as dietary treatments. After 21-23 d, pigs were killed and
      colon digesta and tissue samples analyzed for indices of microbial ecology,
      tissue expression of genes for cell turnover, cytokines, mucus genes (MUC), and
      oxidative stress indices. Pig performance was unaffected by diet. fCP increased
      (P < 0.05) cell counts of clostridia in the Clostridium leptum group and total
      short and branched chain fatty acids, ammonia, putrescine, histamine, and
      spermidine concentrations, whereas high fCHO increased (P < 0.05) cell counts of
      clostridia in the C. leptum and C. coccoides groups, shifted the acetate to
      propionate ratio toward acetate (P < 0.05), and reduced ammonia and putrescine (P
      < 0.05). High dietary fCP increased (P < 0.05) expression of PCNA, IL1beta, IL10,
      TGFbeta, MUC1, MUC2, and MUC20, irrespective of fCHO concentration. The ratio of
      glutathione:glutathione disulfide was reduced (P < 0.05) by fCP and the
      expression of glutathione transferase was reduced by fCHO (P < 0.05). In
      conclusion, fermentable fiber ameliorates fermentable protein-induced changes in
      most measures of luminal microbial ecology but not the mucosal response in the
      large intestine of pigs.

PMID- 22357744
TI  - More evidence is needed for reformulation of fortified blended foods with whey
      protein concentrate.

PMID- 22357745
TI  - Resistant starch from high-amylose maize increases insulin sensitivity in
      overweight and obese men.
AB  - This study evaluated the effects of 2 levels of intake of high-amylose maize type
      2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with
      waist circumference >=89 (women) or >=102 cm (men). Participants received 0
      (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4
      wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end
      of each period using the insulin-modified i.v. glucose tolerance test. The
      efficacy evaluable sample included 11 men and 22 women (mean +/- SEM) age 49.5 +/
      1.6 y, with a BMI of 30.6 +/- 0.5 kg/m2 and waist circumference 105.3 +/- 1.3
      cm. A treatment main effect (P = 0.018) and a treatment * sex interaction (P =
      0.033) were present. In men, least squares geometric mean analysis for S(I) did
      not differ after intake of 15 g/d HAM-RS2 (6.90 * 10-5 pmol-1 . L-1 * min-1) and
      30 g/d HAM-RS2 (7.13 * 10-5 pmol-1 . L-1 * min-1), but both were higher than
      after the control treatment (4.66 * 10-5 pmol-1 . L-1 * min-1) (P < 0.05). In
      women, there was no difference among the treatments (overall least squares ln
      transformed mean +/- pooled SEM = 1.80 +/- 0.08; geometric mean = 6.05 * 10-5
      pmol-1 . L-1 * min-1). These results suggest that consumption of 15-30 g/d of HAM
      RS2 improves S(I) in men. Additional research is needed to understand the
      mechanisms that might account for the treatment * sex interaction observed.

PMID- 22357746
TI  - Whole grain compared with refined wheat decreases the percentage of body fat
      following a 12-week, energy-restricted dietary intervention in postmenopausal
      women.
AB  - Observational studies show inverse associations between intake of whole grain and
      adiposity and cardiovascular risk; however, only a few dietary intervention
      trials have investigated the effect of whole-grain consumption on health
      outcomes. We studied the effect of replacing refined wheat (RW) with whole-grain
      wheat (WW) for 12 wk on body weight and composition after a 2-wk run-in period of
      consumption of RW-containing food intake. In this open-label randomized trial, 79
      overweight or obese postmenopausal women were randomized to an energy-restricted
      diet (deficit of ~1250 kJ/d) with RW or WW foods providing 2 MJ/d. Body weight
      and composition, blood pressure, and concentration of circulating risk markers
      were measured at wk 0, 6, and 12. Fecal output and energy excretion were assessed
      during run-in and wk 12. Plasma alkylresorcinol analysis indicated good
      compliance with the intervention diets. Body weight decreased significantly from
      baseline in both the RW (-2.7 +/- 1.9 kg) and WW (-3.6 +/- 3.2 kg) groups, but
      the decreases did not differ between the groups (P = 0.11). The reduction in body
      fat percentage was greater in the WW group (-3.0%) than in the RW group (-2.1%)
      (P = 0.04). Serum total and LDL cholesterol increased by ~5% (P < 0.01) in the RW
      group but did not change in the WW group; hence, the changes differed between the
      groups (P = 0.02). In conclusion, consumption of whole-grain products resulted in
      a greater reduction in the percentage fat mass, whereas body weight changes did
      not differ between the RW and WW groups. Serum total and LDL cholesterol, two
      important risk factors of cardiovascular disease, increased with RW but not WW
      consumption, which may suggest a cardioprotective role for whole grain.

PMID- 22357747
TI  - Perinatal exposure to vitamin A differentially regulates chondrocyte growth and
      the expression of aggrecan and matrix metalloprotein genes in the femur of
      neonatal rats.
AB  - Vitamin A (VA) and its active form, retinoic acid (RA), are regulators of
      skeletal development. In the present study, we investigated if maternal VA intake
      during pregnancy and lactation, as well as direct oral supplementation of
      neonates with VA + RA (VARA) in early life, alters neonatal bone formation and
      chondrocyte gene expression. Offspring of dams fed 3 levels of VA (marginal,
      adequate, and supplemented) for 10 wk were studied at birth (P0) and postnatal
      day 7 (P7). One-half of the newborns received an oral supplement of VARA on P1,
      P4, and P7. Tissues were collected on P0 and 6 h after the last dose on P7. Pup
      plasma and liver retinol concentrations were increased by both maternal VA intake
      and VARA (P < 0.01). Although maternal VA did not affect bone mineralization as
      assessed by von Kossa staining, newborn femur length was increased with maternal
      VA (P < 0.05). VARA supplementation of neonates increased the length of the
      hypertrophic zone only in VA-marginal pups, close to that in neonates from VA
      adequate dams, suggesting VARA caused a catching up of growth that was limited by
      low maternal VA intake. Maternal diet did not alter type X nor type II collagen
      mRNA. However, VARA-treated pups from VA-supplemented dams had reduced mRNA for
      aggrecan, a major component of cartilage matrix, and increased mRNA for matrix
      metalloproteinase (MMP)13, which catalyzes the degradation of aggrecan and
      collagens. These results suggest that moderately high maternal VA intake combined
      with neonatal VARA supplementation can reduce the ratio of aggrecan:MMP, which
      may unfavorably alter early bone development.

PMID- 22357748
TI  - Infection and pathogenesis of Huaiyangshan virus (a novel tick-borne bunyavirus)
      in laboratory rodents.
AB  - A novel tick-borne bunyavirus (Huaiyangshan virus, HYSV), which causes
      haemorrhagic fever-like disease, has recently been reported in China. So far no
      animal experiments have been performed to study its pathogenesis. Towards
      developing an animal model for HYSV fever, newborn and adult mice and rats and
      golden hamsters were inoculated intracerebrally or intraperitoneally with HYSV.
      Newborn rats and newborn mice, especially Kunming (KM) mice, appeared highly
      susceptible. Remarkably, the KM mice that died of the HYSV infection developed
      large necrotic areas in the liver, while no obvious pathological changes were
      observed within the other organs. PCR and immunohistochemical analyses of the
      post-mortem material detected both HYSV antigen and RNA in almost all organs,
      indicating a systemic infection. Our data demonstrate that HYSV can cause a
      lethal infection of both newborn mice and newborn rats with apparent pathological
      damage of the liver. This animal model may help to understand the pathogenesis of
      the HYSV infection in humans.

PMID- 22357749
TI  - Mapping of functional region conferring nuclear localization and karyopherin
      alpha-binding activity of the C2 protein of bhendi yellow vein mosaic virus.
AB  - Bhendi yellow vein mosaic disease is caused by a complex consisting of a
      monopartite begomovirus associated with a beta-satellite. The C2 protein of
      bhendi yellow vein mosaic virus (BYVMV) is a suppressor of post-transcriptional
      gene silencing and also functions as a transcriptional activator. To explore the
      molecular mechanisms of its nuclear trafficking and self-interaction, fusion
      proteins of fluorescent proteins with wild-type or mutated constructs of BYVMV C2
      were expressed in tobacco protoplasts. Analyses revealed that the BYVMV C2
      nuclear localization signal (NLS) was located in the N terminus of the protein,
      comprising aa 17-31 of C2. NLSs are recognized by a class of soluble transport
      receptors termed karyopherins alpha and beta. The BYVMV C2 NLS was found to be
      necessary for this protein's interaction with its nuclear import mediator,
      karyopherin alpha, ensuring its nuclear localization. Nevertheless, when deleted,
      C2 was found in both the cytoplasm and the nucleus, suggesting NLS-independent
      nuclear import of this protein. Homotypic interaction of BYVMV C2 was also found,
      which correlates with the nuclear localization needed for efficient activation of
      transcription.

PMID- 22357750
TI  - Attenuation of CD4+ T-cell function by human adenovirus type 35 is mediated by
      the knob protein.
AB  - The complement-regulatory protein CD46 is the primary receptor for human
      adenovirus type 35 (HAdV-35) and can regulate human immune-cell activation.
      CD4(+) T-cells are critical for initiating and maintaining adaptive immunity
      elicited by infection or vaccination. It was reported previously that HAdV-35 can
      bind these cells and suppress their activation. The data reported here
      demonstrate that recombinant trimeric HAdV-35 knob proteins alone can induce CD46
      receptor downregulation and inhibit interleukin-2 production and proliferation of
      human CD4(+) T-cells in vitro similarly to mAbs specific to the CD46 region bound
      by HAdV-35 knobs. A mutant knob protein with increased affinity for CD46 compared
      with the wild-type knob caused equivalent effects. In contrast, a CD46-binding
      deficient mutant knob protein did not inhibit T-cell activation. Thus, the
      capacity of HAdV-35 to attenuate human CD4(+) T-cell activation depends
      predominantly on knob interactions with CD46 and can occur independently of
      infection.

PMID- 22357751
TI  - The tale of xenotropic murine leukemia virus-related virus.
AB  - In 2006, a new retrovirus was isolated from prostate cancer patient tissue. Named
      xenotropic murine leukemia virus-related virus (XMRV), this was potentially the
      third class of retrovirus to be pathogenic in humans. XMRV made a more dramatic
      impact on the wider scientific community, and indeed the media, in 2009 when it
      was reported to be present in a remarkably high proportion of patients with
      chronic fatigue syndrome as well as a significant, albeit smaller, proportion of
      healthy controls. The apparent strong link to disease and the fear of a
      previously unknown retrovirus circulating in the general population lead to a
      surge in XMRV research. Subsequent studies failed to find an association of XMRV
      with disease and, in most cases, failed to find the virus in human samples. In
      2011, the case against XMRV and human disease strengthened, ending with several
      decisive publications revealing the origin of the virus and demonstrating
      contamination of samples. In this review, we outline the passage of research on
      XMRV and its potential association with disease from its isolation to the present
      day, where we find ourselves at the end of a turbulent story.

PMID- 22357753
TI  - A systematic review on heart-rate recovery to monitor changes in training status
      in athletes.
AB  - Heart-rate recovery (HRR) has been proposed as a marker of autonomic function and
      training status in athletes. The authors performed a systematic review of studies
      that examined HRR after training. Five cross-sectional studies and 8 studies
      investigating changes over time (longitudinal) met our criteria. Three out of 5
      cross-sectional studies observed a faster HRR in trained compared with untrained
      subjects, while 2 articles showed no change as a result of training. Most
      longitudinal studies observed a corresponding increase in HRR and power output
      (training status). Although confounding factors such as age, ambient temperature,
      and the intensity and duration of the exercise period preceding HRR make it
      difficult to compare these studies, the available studies indicated that HRR was
      related to training status. Therefore, the authors conclude that HRR has the
      potential to become a valuable tool to monitor changes in training status in
      athletes and less well-trained subjects, but more studies and better
      standardization are required to match this potential.

PMID- 22357752
TI  - Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing
      five subtypes and six unclassified lineages with unique geographical
      distributions and genetic variation patterns.
AB  - In this study, we characterized full-length hepatitis C virus (HCV) genome
      sequences for 11 genotype 2 isolates. They were isolated from the sera of 11
      patients residing in Canada, of whom four had an African origin. Full-length
      genomes, each with 18-25 overlapping fragments, were obtained by PCR
      amplification. Five isolates represent the first complete genomes of subtypes 2d,
      2e, 2j, 2m and 2r, while the other six correspond to variants that do not group
      within any assigned subtypes. These sequences had lengths of 9508-9825 nt and
      each contained a single ORF encoding 3012-3106 aa. Predicted amino acids were
      carefully inspected and unique variation patterns were recognized, especially for
      a 2e isolate, QC64. Phylogenetic analysis of complete genome sequences provides
      evidence that there are a total of 16 subtypes, of which 11 have been described
      here. Co-analysis with 68 partial NS5B sequences also differentiated 18 assigned
      subtypes, 2a-2r, and eight additional lineages within genotype 2, which is
      consistent with the analysis of complete genome sequences. The data from this
      study will now allow 10 assigned subtypes and six additional lineages of HCV
      genotype 2 to have their full-length genomes defined. Further analysis with 2021
      genotype 2 sequences available in the HCV database indicated that the
      geographical distribution of these subtypes is consistent with an African origin,
      with particular subtypes having spread to Asia and the Americas.

PMID- 22357754
TI  - Special issue of child maltreatment on implementation: some key developments in
      evidence-based models for the treatment of child maltreatment.

PMID- 22357756
TI  - A core erythroid transcriptional network is repressed by a master regulator of
      myelo-lymphoid differentiation.
AB  - Two mechanisms that play important roles in cell fate decisions are control of a
      "core transcriptional network" and repression of alternative transcriptional
      programs by antagonizing transcription factors. Whether these two mechanisms
      operate together is not known. Here we report that GATA-1, SCL, and Klf1 form an
      erythroid core transcriptional network by co-occupying >300 genes. Importantly,
      we find that PU.1, a negative regulator of terminal erythroid differentiation, is
      a highly integrated component of this network. GATA-1, SCL, and Klf1 act to
      promote, whereas PU.1 represses expression of many of the core network genes.
      PU.1 also represses the genes encoding GATA-1, SCL, Klf1, and important GATA-1
      cofactors. Conversely, in addition to repressing PU.1 expression, GATA-1 also
      binds to and represses >100 PU.1 myelo-lymphoid gene targets in erythroid
      progenitors. Mathematical modeling further supports that this dual mechanism of
      repressing both the opposing upstream activator and its downstream targets
      provides a synergistic, robust mechanism for lineage specification. Taken
      together, these results amalgamate two key developmental principles, namely,
      regulation of a core transcriptional network and repression of an alternative
      transcriptional program, thereby enhancing our understanding of the mechanisms
      that establish cellular identity.

PMID- 22357757
TI  - Protein disulfide isomerase homolog PDILT is required for quality control of
      sperm membrane protein ADAM3 and male fertility [corrected].
AB  - A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein
      critical for both sperm migration from the uterus into the oviduct and sperm
      primary binding to the zona pellucida (ZP). Here we show that the testis-specific
      protein disulfide isomerase homolog (PDILT) cooperates with the testis-specific
      calreticulin-like chaperone, calsperin (CALR3), in the endoplasmic reticulum and
      plays an indispensable role in the disulfide-bond formation and folding of ADAM3.
      Pdilt(-/-) mice were male infertile because ADAM3 could not be folded properly
      and transported to the sperm surface without the PDILT/CALR3 complex. Peculiarly
      we find that not only Pdilt(-/-), but also Adam3(-/-), spermatozoa effectively
      fertilize eggs when the eggs are surrounded in cumulus oophorus. These findings
      reveal that ADAM3 requires testis-specific private chaperones to be folded
      properly and that the principle role of ADAM3 is for sperm migration into the
      oviduct but not for the fertilization event. Moreover, the importance of primary
      sperm ZP binding, which has been thought to be a critical step in mammalian
      fertilization, should be reconsidered.

PMID- 22357758
TI  - Calcium-based plasticity model explains sensitivity of synaptic changes to spike
      pattern, rate, and dendritic location.
AB  - Multiple stimulation protocols have been found to be effective in changing
      synaptic efficacy by inducing long-term potentiation or depression. In many of
      those protocols, increases in postsynaptic calcium concentration have been shown
      to play a crucial role. However, it is still unclear whether and how the dynamics
      of the postsynaptic calcium alone determine the outcome of synaptic plasticity.
      Here, we propose a calcium-based model of a synapse in which potentiation and
      depression are activated above calcium thresholds. We show that this model gives
      rise to a large diversity of spike timing-dependent plasticity curves, most of
      which have been observed experimentally in different systems. It accounts
      quantitatively for plasticity outcomes evoked by protocols involving patterns
      with variable spike timing and firing rate in hippocampus and neocortex.
      Furthermore, it allows us to predict that differences in plasticity outcomes in
      different studies are due to differences in parameters defining the calcium
      dynamics. The model provides a mechanistic understanding of how various
      stimulation protocols provoke specific synaptic changes through the dynamics of
      calcium concentration and thresholds implementing in simplified fashion protein
      signaling cascades, leading to long-term potentiation and long-term depression.
      The combination of biophysical realism and analytical tractability makes it the
      ideal candidate to study plasticity at the synapse, neuron, and network levels.

PMID- 22357759
TI  - Self-incompatibility response induced by calcium increase in sperm of the
      ascidian Ciona intestinalis.
AB  - Many hermaphroditic organisms possess a self-incompatibility system to avoid self
      fertilization. Recently, we identified the genes responsible for self-sterility
      in a hermaphroditic primitive chordate (ascidian), Ciona intestinalis: sperm-side
      polycystin 1-like receptors s-Themis-A/B and egg-side fibrinogen-like ligands on
      the vitelline coat (VC) v-Themis-A/B. Here, we investigated the sperm behavior
      and intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to self/nonself
      recognition. We found that sperm motility markedly decreased within 5 min after
      attachment to the VC of self-eggs but not after attachment to the VC of nonself
      eggs and that the apparent decrease in sperm motility was suppressed in low
      Ca(2+) seawater. High-speed video analysis revealed that sperm detached from the
      self-VC or stopped motility within 5 min after binding to the self-VC. Because s
      Themis-B contains a cation channel domain in its C terminus, we monitored sperm
      [Ca(2+)](i) by real-time [Ca(2+)](i) imaging using Fluo-8H-AM (AAT Bioquest,
      Inc.). Interestingly, we found that sperm [Ca(2+)](i) rapidly and dramatically
      increased and was maintained at a high level in the head and flagellar regions
      when sperm interacted with the self-VC but not when the sperm interacted with the
      nonself-VC. The increase in [Ca(2+)](i) was also suppressed by low-Ca(2+)
      seawater. These results indicate that the sperm self-recognition signal triggers
      [Ca(2+)](i) increase and/or Ca(2+) influx, which elicits a self-incompatibility
      response to reject self-fertilization in C. intestinalis.

PMID- 22357760
TI  - Nonovarian origins of ovarian cancer.

PMID- 22357761
TI  - Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding.
AB  - Von Willebrand factor (VWF) is a large, multimeric plasma glycoprotein that
      critically mediates hemostasis at sites of vascular injury. Very large VWF
      multimers have the greatest thrombogenic activity, which is attenuated by
      cleavage in the A2 domain by the metalloproteinase ADAMTS13. ADAMTS13 proteolysis
      requires mechanical force to expose the scissile bond and is regulated by a
      calcium-binding site within A2. In this study, we characterized the interaction
      between VWF A2 and calcium by examining the effect of calcium on VWF A2 stability
      and mechanical unfolding and refolding. Isothermal calorimetry yielded a calcium
      binding K(d) = 3.8 +/- 1.0 MUM and reversible thermal denaturation showed that 5
      mM calcium stabilized the unfolding transition from 56.7 +/- 0.1 to 69.1 +/- 0.1 
      degrees C. Using optical tweezers to apply tensile force to single domains, we
      found that calcium did not affect VWF A2 unfolding, but rather enhanced refolding
      kinetics fivefold, resulting in a 0.9 kcal/mol stabilization in the folding
      activation energy in the presence of calcium. Taken together, our data
      demonstrate that VWF binds calcium at physiologic calcium concentrations and that
      calcium stabilizes VWF A2 by accelerating refolding.

PMID- 22357762
TI  - Iterative approach to computational enzyme design.
AB  - A general approach for the computational design of enzymes to catalyze arbitrary
      reactions is a goal at the forefront of the field of protein design. Recently,
      computationally designed enzymes have been produced for three chemical reactions
      through the synthesis and screening of a large number of variants. Here, we
      present an iterative approach that has led to the development of the most
      catalytically efficient computationally designed enzyme for the Kemp elimination
      to date. Previously established computational techniques were used to generate an
      initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with
      molecular dynamics simulations (MD) and X-ray crystallography indicated that the
      inactivity might be due to bound waters and high flexibility of residues within
      the active site. This analysis guided changes to our design procedure, moved the
      design deeper into the interior of the protein, and resulted in an active Kemp
      eliminase, HG-2. The cocrystal structure of this enzyme with a transition state
      analog (TSA) revealed that the TSA was bound in the active site, interacted with
      the intended catalytic base in a catalytically relevant manner, but was flipped
      relative to the design model. MD analysis of HG-2 led to an additional point
      mutation, HG-3, that produced a further threefold improvement in activity. This
      iterative approach to computational enzyme design, including detailed MD and
      structural analysis of both active and inactive designs, promises a more complete
      understanding of the underlying principles of enzymatic catalysis and furthers
      progress toward reliably producing active enzymes.

PMID- 22357763
TI  - Resolvent positive linear operators exhibit the reduction phenomenon.
AB  - The spectral bound, s(alphaA + betaV), of a combination of a resolvent positive
      linear operator A and an operator of multiplication V, was shown by Kato to be
      convex in beta ? R. Kato's result is shown here to imply, through an elementary
      "dual convexity" lemma, that s(alphaA + betaV) is also convex in alpha > 0, and
      notably, ?s(alphaA + betaV)/?alpha <= s(A). Diffusions typically have s(A) <= 0,
      so that for diffusions with spatially heterogeneous growth or decay rates,
      greater mixing reduces growth. Models of the evolution of dispersal in particular
      have found this result when A is a Laplacian or second-order elliptic operator,
      or a nonlocal diffusion operator, implying selection for reduced dispersal. These
      cases are shown here to be part of a single, broadly general, "reduction"
      phenomenon.

PMID- 22357764
TI  - Final-ART success rates: a 10 years survey.

PMID- 22357765
TI  - Congenital heart defects and parental occupational exposure to chemicals.
AB  - BACKGROUND: Congenital heart defects (CHDs) are the most common major
      malformations in newborns. In this study we examined the associations between the
      occurrence of CHDs in children and periconceptional occupational parental
      exposures to chemicals. METHODS: In an age-matched case-control study with
      standardized data collection at c. 15 months after birth, 424 mothers and 421
      fathers of a child with CHD and 480 mothers and 477 fathers of a non-malformed
      child, filled out questionnaires on periconceptional general and job
      characteristics. A job exposure matrix, which links the information on job title
      and a description of work tasks to an expert judgement on exposure to chemicals
      in the workplace, was used. RESULTS: The overall prevalence of occupational
      exposure to chemicals was 5.0 in cases and 6.2% in controls for mothers [odds
      ratio (OR) adjusted = 0.92; 95% confidence interval (CI): 0.26-3.25], while 22.3
      and 15.9% for fathers, respectively (OR adjusted = 1.23; 95% CI: 0.39-3.91). No
      association of maternal occupational exposure to chemicals with risk of CHDs was
      found. Paternal exposure to phthalates was associated with a higher incidence of
      CHDs in general (OR adjusted = 2.08; 95% CI: 1.27-3.40). Paternal exposure to
      phthalates was associated with perimembranous ventricular septal defect (OR
      adjusted = 2.84; 95% CI: 1.37-5.92), to polychlorinated compounds with
      atrioventricular septal defect (OR adjusted = 4.22; 95% CI: 1.23-14.42) and to
      alkylphenolic compounds with coarctation of the aorta (OR adjusted = 3.85; 95%
      CI: 1.17-12.67). CONCLUSIONS: Periconceptional paternal (but not maternal)
      occupational exposure to certain chemicals is associated with an increased risk
      of CHDs in children. The results, however, must be interpreted cautiously as
      exposure probabilities are a crude measure of exposure.

PMID- 22357766
TI  - Prevalence of elevated glycated hemoglobin in women with polycystic ovary
      syndrome.
AB  - BACKGROUND: Recently, the American Diabetes Association (ADA) has included
      glycated hemoglobin A1(c) (A1C) level as a component of diagnostic criteria of
      'diabetes' or 'increased risk for diabetes'. This study was conducted to examine
      the prevalence of and risk factors for 'elevated A1C' (>=5.7%) in women with
      polycystic ovary syndrome (PCOS). METHODS: A1C was measured using an
      immunoturbidimetric assay, and was evaluated in 154 patients with PCOS and 469
      age-matched controls (match ratio of 1-3). All subjects were categorized by BMI
      (non-obese <25 kg/m(2) and obese >=25 kg/m(2)), and the prevalence of elevated
      A1C was also analyzed according to BMI. RESULTS: One-third (31.2%) of the
      patients with PCOS had elevated A1C. The prevalence of elevated A1C (>=5.7%) was
      similar in obese women with PCOS and obese controls (23.5 and 20.0%,
      respectively, P= 1.0) but non-obese women with PCOS (mean age 29.8 +/- 5.3 years)
      had a higher prevalence of elevated A1C than non-obese controls (31.2 versus
      6.6%, respectively, P< 0.001). Logistic regression analysis of all subjects
      showed that the odds that a woman has elevated A1C was 6.7 times higher if she
      has PCOS (adjusted odds ratio 6.67, 95% confidence interval 3.50-12.70).
      CONCLUSIONS: The high prevalence of elevated A1C in non-obese patients with PCOS
      and an increased risk of elevated A1C associated with PCOS suggest that PCOS
      itself may be associated with abnormal A1C status. Assessing A1C level in young,
      non-obese patients with PCOS may be a useful new approach to screening for
      diabetes.

PMID- 22357767
TI  - Diet-induced paternal obesity in the absence of diabetes diminishes the
      reproductive health of two subsequent generations of mice.
AB  - BACKGROUND: Obesity and related conditions, notably subfertility, are
      increasingly prevalent. Paternal influences are known to influence offspring
      health outcome, but the impact of paternal obesity and subfertility on the
      reproductive health of subsequent generations has been overlooked. METHODS: A
      high-fat diet (HFD) was used to induce obesity but not diabetes in male C57Bl6
      mice, which were subsequently mated to normal-weight females. First-generation
      offspring were raised on a control diet and their gametes were investigated for
      signs of subfertility. Second-generation offspring were generated from both first
      generation sexes and their gametes were similarly assessed. RESULTS: We
      demonstrate a HFD-induced paternal initiation of subfertility in both male and
      female offspring of two generations of mice. Furthermore, we have shown that
      diminished reproductive and gamete functions are transmitted through the first
      generation paternal line to both sexes of the second generation and via the first
      generation maternal line to second-generation males. Our previous findings that
      founder male obesity alters the epigenome of sperm, could provide a basis for the
      developmental programming of subfertility in subsequent generations. CONCLUSIONS:
      This is the first observation of paternal transmission of diminished reproductive
      health to future generations and could have significant implications for the
      transgenerational amplification of subfertility observed worldwide in humans.

PMID- 22357768
TI  - No evidence that assisted reproduction increases the risk of thrombosis: a Danish
      national cohort study.
AB  - BACKGROUND: Case reports have reported venous and arterial thromboses in women
      undergoing assisted reproduction. No large systematic studies on the risk of
      thrombosis have been published. The objective of our study was to investigate
      whether the risk of thrombosis is increased in women undergoing assisted
      reproduction. METHODS: A national register-based cohort study was conducted on
      all women undergoing IVF or ICSI treatment in Denmark from 1994 to 2005. Data
      were obtained from the National Patient Registry and the IVF Registry. Women with
      prior malignant or cardiovascular disease were excluded. Thrombosis occurring
      within the first 6 and 12 months after assisted reproduction was considered
      potentially related to the treatment. Thromboses during pregnancy as well as the
      pregnancy-related diagnoses were excluded from the statistical analysis. The
      incidence rates of venous and arterial thromboses were compared with previously
      published estimates of the risk of thrombosis among young Danish women. RESULTS:
      We analyzed 30 884 Danish women undergoing 75 141 treatments from 1994 to 2005.
      The mean age of the women at first treatment was 32.3 years. The delivery rate
      per cycle was 22%. The incidence rate ratio, with 95% confidence interval (CI),
      of venous thrombosis within 6 months was 0.95 (CI: 0.38-1.95). The incidence rate
      ratio of arterial thrombosis within 6 months was 0.36 (CI: 0.04-1.30).
      CONCLUSIONS: Our study showed no evidence that assisted reproduction increases
      the risk of thrombosis.

PMID- 22357769
TI  - Depleted iron stores without anaemia early in pregnancy carries increased risk of
      lower birthweight even when supplemented daily with moderate iron.
AB  - BACKGROUND: Gestational iron-deficiency anaemia has adverse pregnancy outcomes.
      Antenatal iron supplementation can be beneficial in anaemic women, but the
      effects in non-anaemic women are controversial. This observational study assessed
      the relationship of maternal iron stores (depleted or non-depleted) at
      gestational Weeks 8-12 with birthweight, in non-anaemic pregnant women following
      the guidelines of the Ministry of Health of Spain. METHODS: Healthy, non-anaemic
      pregnant women (n = 205) were studied. At the first antenatal visit, a general
      clinical assessment was conducted, and basal blood taken. Women were classified
      as having non-depleted or depleted iron stores [serum ferritin (SF) < 12 ug/l)].
      Daily antenatal iron supplements (48 mg on average) were started at 17 (range: 16
      18) weeks. Blood haemoglobin, SF and transferrin saturation (TS) were measured in
      each trimester. RESULTS: Of the study sample, 20, 54 and 66% had SF < 12 ug/l in
      the first, second and third trimesters, respectively. The prevalence of iron
      depletion (SF < 12 ug/l) and iron-deficiency (SF < 12 ug/l and TS < 16%) was
      greater during the entire pregnancy in women with initial iron depletion versus
      no depletion (81.6 and 73.7% versus 61.7 and 55.4%, respectively, in the third
      trimester, P < 0.05). Women with initial iron-depletion delivered babies weighing
      on average 192 g less than that with initial iron stores, after adjusting for
      confounding variables (P = 0.028). CONCLUSIONS: Beginning pregnancy with non
      depleted iron stores is beneficial for the maternal iron status during pregnancy
      and infant birthweight. These findings reaffirm the importance of health
      promotion to ensure that women have adequate iron stores prior to, or early in,
      pregnancy when supplemented with moderate daily iron doses.

PMID- 22357770
TI  - Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC).
AB  - BACKGROUND: Ovarian aging is associated with declining numbers and quality of
      oocytes and follicles. Oxidative stress by reactive oxygen species (ROS)
      contributes to somatic aging in general, and also has been implicated in
      reproductive aging. Telomere shortening is also involved in aging, and telomeres
      are particularly susceptible to ROS-induced damage. Previously, we have shown
      that antioxidant N-acetyl-L-cysteine (NAC) effectively rescues oocytes and
      embryos from ROS-induced telomere shortening and apoptosis in vitro. Using mice
      as models, we tested the hypothesis that reducing oxidative stress by NAC might
      prevent or delay ovarian aging in vivo. METHODS: Initially, young females were
      treated with NAC in drinking water for 2 months and the quality of fertilized
      oocytes and early embryo development were evaluated. Next, young mice 1-11/2
      months old were treated for 1 year with NAC added in drinking water, and their
      fertility was analyzed starting at 6 months, as indicated by litter size, oocyte
      number and quality. The ovaries were also examined for telomere activity and
      length and the expression of selected genes related to aging and DNA damage.
      RESULTS: Short-term treatment of mice for 2 months with NAC demonstrated that NAC
      improved the quality of fertilized oocytes and early embryo development. Mice
      treated with a long-term low concentration (0.1 mM) of NAC had increased litter
      sizes at the ages of 7-10 months compared with age-matched controls without NAC
      treatment. NAC also increased the quality of the oocytes from these older mice.
      Moreover, the expression of sirtuins was increased, telomerase activity was
      higher and telomere length was longer in the ovaries of mice treated with NAC
      compared with those of the control group. CONCLUSIONS: These data suggest that
      appropriate treatment with the antioxidant NAC postpones the process of oocyte
      aging in mice.

PMID- 22357771
TI  - Oocyte cryopreservation for age-related fertility loss.
AB  - The recent introduction of oocyte vitrification has significantly advanced the
      outcome of oocyte cryopreservation, leading to clinical results comparable to
      those achieved in IVF using fresh oocytes, as reported by experienced centres.
      This has lead to new debate, both in the professional community and in society at
      large, about the acceptability of offering this technology to reproductively
      healthy women who want to cryopreserve their oocytes against the threat of time.
      Given the many demands calling for simultaneous realization in a relatively short
      period of their lives, many women who want to have children feel to be under
      considerable pressure. The option of oocyte cryopreservation may in fact give
      them more breathing space. In this document, it is concluded that the arguments
      against allowing this application of the technology are not convincing. The
      recommendations include the need for adequate information of women interested in
      oocyte cryopreservation, also in order to avoid raising false hopes. The message
      must remain that women's best chances of having a healthy child are through
      natural reproduction at a relative early age. Centres offering this service must
      have the necessary expertise to employ oocyte cryopreservation efficiently with
      the so far non-standardized protocols. As data about long-term safety is still
      lacking, centres also have a responsibility to contribute to the collection of
      these data.

PMID- 22357772
TI  - 'Zero is not good for me': implications of infertility in Ghana.
AB  - BACKGROUND: Given the high value placed on children in sub-Saharan Africa,
      previous research suggests that infertility increases the risk of psychological
      distress and marital conflict, encourages risky sexual behavior and deprives
      infertile individuals and couples of an important source of economic and social
      capital. This paper explores the implications of infertility for women in Ghana,
      West Africa. METHODS: Semi-structured interview data collected from 107 women
      (aged 21-48 years, mean 33 years) seeking treatment in gynecological and
      obstetric clinics in Accra, Ghana, are analyzed. Based on iterative open coding
      of the interviews, the focus of the analysis is on mental health, marital
      instability, social interaction and gendered experiences. RESULTS: Infertile
      women report facing severe social stigma, marital strain and a range of mental
      health difficulties. Many women feel that they shoulder a disproportionate share
      of the blame for infertility and, by extension, face greater social consequences
      than male partners for difficulties conceiving. Women who do not self-identify as
      infertile corroborate these findings, asserting that the social consequences of
      infertility are severe, particularly for women. CONCLUSIONS: Infertility in Ghana
      has important consequences for social interactions, marital stability and mental
      health. These consequences are not perceived to be shared equally by Ghanaian
      men.

PMID- 22357773
TI  - Empty follicle syndrome: successful treatment in a recurrent case and review of
      the literature.
AB  - Empty follicle syndrome is a condition in which no oocytes are retrieved after an
      apparently adequate ovarian response to stimulation and meticulous follicular
      aspiration. It is a rare condition of obscure etiology. A patient with primary
      infertility who underwent seven assisted reproductive technique cycles is
      described. In spite of a satisfactory ovarian response, aspiration yielded no
      oocytes in four cycles and 1-4 low quality oocytes in three cycles. In the index
      treatment cycle, ovulation was triggered using GnRH agonist 40 h prior to ovum
      pickup and hCG was added 6 h after the first trigger. Eighteen oocytes were
      recovered, of which 16 were mature and were inseminated by ICSI. Two embryos were
      transferred 48 h after aspiration and nine embryos were cryopreserved. The
      patient conceived and delivered a healthy boy at 38 weeks of gestation. The
      literature is reviewed and possible etiologies and treatment options of this
      enigmatic syndrome are suggested.

PMID- 22357774
TI  - Potential role of urinary angiotensinogen in predicting antiproteinuric effects
      of angiotensin receptor blocker in non-diabetic chronic kidney disease patients:
      a preliminary report.
AB  - OBJECTIVES: Many chronic kidney disease (CKD) patients have persistent overt
      proteinuria despite angiotensin receptor blocker (ARB) treatment. This study
      investigated whether the initial difference in intrarenal renin-angiotensin
      system activity measured with urinary angiotensinogen would affect the
      antiproteinuric effects of ARB. METHODS: Between September 2005 and September
      2008, in 50 non-diabetic proteinuric CKD patients not taking renin-angiotensin
      system inhibitors, the urinary protein/creatinine ratio (P/Cr),
      angiotensinogen/creatinine ratio (AGT/Cr), plasma renin and aldosterone were
      measured before starting valsartan, and were followed for 18 months. RESULTS:
      Patients were divided into three groups according to their initial urinary
      AGT/Cr. The urinary P/Cr was lower in the low angiotensinogen group, but similar
      in the high and extremely high angiotensinogen groups (1.3+/-0.38 vs 2.0+/-0.92
      vs 2.2+/-0.78). In all groups, the urinary P/Cr was decreased most for the first
      6 months. The urinary P/Cr reduction at 6 months was greatest in the high
      angiotensinogen group (-24.2% vs -46.2% vs -16.4%). The urinary AGT/Cr was
      decreased most in the high angiotensinogen group. Renal functional deterioration
      was attenuated in the high angiotensinogen group compared with the extremely high
      angiotensinogen group. CONCLUSIONS: The antiproteinuric effects of ARB were
      different according to the initial urinary angiotensinogen levels. These results
      suggest the potential value of the initial urinary AGT/Cr for predicting the
      therapeutic effect of ARB in proteinuric non-diabetic CKD patients.

PMID- 22357775
TI  - Advances in antiplatelet therapy for acute coronary syndromes.
AB  - Admissions to emergency care centres with acute coronary syndromes remain one of
      the principal burdens on healthcare systems in the Western world. Early
      pharmacological treatment in these patients is crucial, lessening the impact on
      both morbidity and mortality, with the cornerstone of management being
      antiplatelet agents. While aspirin and clopidogrel have been the drugs of choice
      for nearly a decade, an array of newer, more potent antiplatelet agents are now
      available or in late stage development. Data are rapidly gathering suggesting
      these agents have superior anti-ischaemic properties, improving patient outcomes,
      but that for some agents increased vigilance and appropriate patient selection
      may be necessary to guard against bleeding complications. In this review, the
      authors aim to deliver an overview of the changing field of antiplatelet therapy
      and provide information about the relative risks and benefits of these newer
      agents, many of which will be entering widespread clinical use imminently.

PMID- 22357776
TI  - Streptococcus tigurinus sp. nov., isolated from blood of patients with
      endocarditis, meningitis and spondylodiscitis.
AB  - Four Gram-stain-positive, catalase-negative, coccus-shaped bacterial strains were
      isolated from multiple blood cultures of patients with endocarditis, meningitis
      and spondylodiscitis. The isolates were tentatively identified as viridans
      streptococci on the basis of phenotypic characteristics. Comparative 16S rRNA
      gene sequencing studies showed that the organisms were members of the
      Streptococcus mitis group but did not correspond to any recognized species. The
      nearest phylogenetic relative was S. mitis ATCC 49456(T), with 98.6% sequence
      similarity. The representative strain AZ_3a(T) showed less than 96.8, 97.6, 94.5
      and 95.5% similarity to the phylogenetically most closely related species by
      recA, rpoB, sodA and groEL gene sequence analysis, respectively. DNA-DNA
      hybridization analyses showed a low reassociation value of 32.2% between strain
      AZ_3a(T) and S. mitis DSM 12643(T). Reassociation values with members of other S.
      mitis group species ranged from 27.3 to 49.7%. The G+C content of the DNA was
      40.0 mol%. Based on our biochemical and molecular analyses, the isolates
      represent a novel species, for which the name Streptococcus tigurinus sp. nov. is
      proposed. The type strain is AZ_3a(T) ( = CCOS 600(T)  = DSM 24864(T)).

PMID- 22357777
TI  - Learning from near misses: from quick fixes to closing off the Swiss-cheese
      holes.
AB  - INTRODUCTION: The extent to which individuals in healthcare use near misses as
      learning opportunities remains poorly understood. Thus, an exploratory study was
      conducted to gain insight into the nature of, and contributing factors to,
      organisational learning from near misses in clinical practice. METHODS: A
      constructivist grounded theory approach was employed which included semi
      structured interviews with 24 participants (16 clinicians and 8 administrators)
      from a large teaching hospital in Canada. RESULTS: This study revealed three
      scenarios for the responses to near misses, the most common involved 'doing a
      quick fix' where clinicians recognised and corrected an error with no further
      action. The second scenario consisted of reporting near misses but not hearing
      back from management, which some participants characterised as 'going into a
      black hole'. The third scenario was 'closing off the Swiss-cheese holes', in
      which a reported near miss generated corrective action at an organisational
      level. Explanations for 'doing a quick fix' included the pervasiveness of near
      misses that cause no harm and fear associated with reporting the near miss.
      'Going into a black hole' reflected managers' focus on operational duties and
      events that harmed patients. 'Closing off the Swiss-cheese holes' occurred when
      managers perceived substantial potential for harm and preventability. Where
      learning was perceived to occur, leaders played a pivotal role in encouraging
      near-miss reporting. CONCLUSION: To optimise learning, organisations will need to
      determine which near misses are appropriate to be responded to as 'quick fixes'
      and which ones require further action at the unit and corporate levels.

PMID- 22357778
TI  - Getting doctors to clean their hands: lead the followers.
AB  - BACKGROUND: Despite ample evidence that hand hygiene (HH) can reduce nosocomial
      infections, physician compliance remains low. The authors hypothesised that
      attending physician role modelling and peer pressure among internal medicine
      teams would impact HH adherence. METHODS: Nine teams were covertly observed. Team
      member entry and exit order, and adherence to HH were recorded secretly. The mean
      HH percentage across encounters was estimated by compliance of the first person
      entering and exiting an encounter, and by the attending physician's HH
      compliance. RESULTS: 718 HH opportunities prior to contact and 744 opportunities
      after contact were observed. If the first person entering a patient encounter
      performed HH, the mean compliance of other team members was 64%, but was only 45%
      if the first person failed to perform HH (p=0.002). When the attending physician
      performed HH upon entering the patient encounter, the mean HH compliance was 66%,
      but only 42% if the attending physician did not perform HH (p<0.001). Similar
      results were seen on exiting the room. The effects of the first person were not
      driven solely by the attending physician's HH behaviour because the attending
      physician was first or second to enter 57% of the encounters and exit 44% of the
      encounters. CONCLUSIONS: If the first person entering a patient room performs HH,
      then others were more likely to perform HH too, implying that peer pressure
      impacts team member HH compliance. The attending physician's behaviour also
      influenced team members regardless of whether the attending physician was the
      first to enter or exit an encounter, implying that role modelling impacts the HH
      behaviour of learners. These findings should be used when designing HH
      improvement programmes targeting physicians.

PMID- 22357779
TI  - Cluster analysis of symptoms in pulmonary arterial hypertension: a pilot study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by elevated
      pulmonary artery pressures leading to right heart failure and death. AIMS: The
      aim of this study was to use cluster analysis to describe the symptom profile in
      PAH and differences in the health outcomes of health status, health-related
      quality of life (HRQoL) and psychological states in the cluster groups. METHODS:
      A cross-sectional descriptive design was used. A convenience sample completed a
      socio-demographic and clinical data form, a PAH Symptom Severity and Interference
      Scale, the Medical Outcomes Study Short Form (SF-36), the United States Cambridge
      Pulmonary Hypertension Outcome Review (US CAMPHOR) and the Short Form of the
      Profile of Mood States (POMS). RESULTS: Of the 151 participants, the mean age was
      53.5 +/- 15.1 with the majority female (n = 128, 85%). Fifty-eight (41%) were
      disabled and 67 (44%) were Functional Class IV. The most prevalent symptoms were
      shortness of breath with exertion (n = 149, 99%) and fatigue (n = 144, 93%).
      Three clusters emerged: Cluster 1 diffuse symptoms (n = 93), Cluster 2 severe
      cardiopulmonary symptoms (n = 32) and Cluster 3 moderate cardiopulmonary symptoms
      (n = 26). Overall, on the SF-36 the participants had poor general health, reduced
      physical function, role physical, vitality, and a low composite score for
      physical health. On the POMS the sample had limited vigor and increased fatigue.
      Cluster 2 Severe Cardiopulmonary Symptoms had worse SF-36, US CAMPHOR and POMS
      scores than the other cluster groups. CONCLUSIONS: Patients with PAH are
      experiencing a constellation of symptoms that are interfering with their life and
      emerging clusters were present.

PMID- 22357780
TI  - Caring for the radial artery post-angiogram: a pilot study on a comparison of
      three methods of compression.
AB  - BACKGROUND: A coronary angiogram, a diagnostic tool to visualize the coronary
      anatomy, has traditionally been accessed through the femoral artery. However, in
      the last 20 years, the radial artery has gained more popularity among physicians
      and patients, offering an alternative to the femoral approach. Various methods of
      applying compression to the radial puncture site have been used, but no research
      has been done to demonstrate the most effective way of achieving hemostasis while
      limiting complications and ensuring the efficient use of nursing and medical
      resources. OBJECTIVE: The purpose of this pilot study was to compare two devices
      and three methods for achieving hemostasis after a transradial angiogram while
      assessing vascular complications and time endpoints. DESIGN AND METHODS: A
      mechanical device (TerumoTM wristband) and a hydrophilic wound dressing (Clo-Sur
      P.A.D.) were used. The Terumo band was studied twice, using the current method
      and a fast-release method. RESULTS: Taking into account the small sample size of
      this pilot study (N = 25 per group), statistically significant differences (p <=
      0.005) are seen in time to discharge in the fast-release Terumo (134.0 minutes)
      and Clo-Sur P.A.D. groups (113.7 minutes), as compared with the control Terumo
      group (178.2 minutes), without increasing vascular complications.

PMID- 22357781
TI  - Factors influencing the presence of peripheral arterial disease among Thai
      patients with type 2 diabetes.
AB  - BACKGROUND: Little is known about factors predicting peripheral arterial disease
      (PAD) development in Thai type 2 diabetes patients. This study aims to identify
      factors related to PAD in type 2 diabetes and the best predictors for PAD
      development. METHODS AND RESULTS: A case-control study was conducted in which 405
      type 2 diabetes patients were recruited from four tertiary care hospitals in
      Bangkok, Thailand. Cases were type 2 diabetes patients with PAD who were compared
      to those without PAD. An ankle-brachial index (ABI) < 0.9 was used for PAD
      diagnosis. An ABI between 0.91 and 1.30 was used to define those without PAD.
      Demographic characteristics, the diabetes self-care activities score and chief
      complaints were measured. Thai type 2 diabetes patients with PAD were older
      (65.45 +/- 12.2 years), had no formal schooling, and were more likely to be a
      local vendor than those without PAD (p < 0.05). Type 2 diabetes patients with PAD
      had diabetes longer than those without PAD (p < 0.05). Hypertension, coronary
      heart disease and chronic kidney disease were significantly more common in type 2
      diabetes patients with PAD than those without PAD (p < 0.05). Age > 70 years,
      having coronary heart disease as a comorbid illness, and having a body mass index
      of 25-29.9 kg/m(2) were predictive for PAD development (all p < 0.05). These
      three variables explained 12.3% of the variance in the incidence of PAD among
      type 2 diabetes patients. The demographic and clinical factors were the best
      predictors for PAD development. CONCLUSION: Thai type 2 diabetes patients who are
      elderly, have coronary heart disease as a comorbid condition, or have a normal
      weight should be considered at risk for PAD development.

PMID- 22357782
TI  - Measuring knowledge of patients with congenital heart disease and their parents:
      validity of the 'Leuven Knowledge Questionnaire for Congenital Heart Disease'.
AB  - BACKGROUND: Patients with congenital heart disease (CHD) and their parents need
      to have sufficient knowledge on their condition, treatment, medication, and
      preventive measures. The Leuven Knowledge Questionnaire for Congenital Heart
      Disease (LKQCHD) was developed to comprehensively measure the level of knowledge
      in patients with CHD. AIMS: This study aimed to translate the LKQCHD into Chinese
      and to test its validity to be used in patients with CHD and their parents.
      METHOD: Questionnaire translation was guided by a three-step linguistic
      validation method. Evidence based on test content and on relation with other
      variables was obtained. For test content, we included five experts in CHD and
      research methods. Furthermore, the instrument was tested in 89 pairs of
      adolescents with CHD and their parents. RESULTS: We found a high item-level
      content validity index (>0.78 in all except two items), high scale-level content
      validity index (>0.90), high free-marginal multirater Kappa (>0.75), and low
      average proportion of missing values (0.49% in adolescents; 0.51% in parents),
      showing an excellent content validity. The hypothesized positive correlations
      between parental knowledge and parental educational level and between patient's
      knowledge and patient's age, as well as the hypothesis that parents have more
      knowledge than their children, were confirmed. This provides validity evidence
      based on relation with other variables. CONCLUSIONS: The Chinese version of the
      LKQCHD is valid to assess the level of knowledge in patients with CHD and their
      parents.

PMID- 22357783
TI  - Pain management after cardiac surgery: experience with a nurse-driven pain
      protocol.
AB  - OBJECTIVE: Management of post-operative pain is important for decreasing post
      operative morbidity and mortality. After evaluating our pain score database of
      patients undergoing cardiac surgery (2007-2009) we revised our pain protocol. The
      new protocol allows nurses to administer analgesic medication without consulting
      the attending physician. The setting was a medium care unit, a nursing ward with
      additional monitoring of heart rate and rhythm. We investigated the effects of
      this revised pain protocol in a prospective consecutive cohort study. METHODS: We
      evaluated 193 patients treated according to the revised protocol (RP group)
      during the first 72 hours post-cardiac surgery on the medium care unit. A visual
      analogue scale (VAS) was used as pain scoring system. These patients were
      compared with a control group (Ctrl group) consisting of 1535 patients. RESULTS:
      Patients from the RP group had a mean VAS of 2.2 compared to a mean VAS of 2.8 in
      the Ctrl group (p < 0.0001). In the Ctrl group 44% of patients with a VAS >= 4
      maintained this score for 8 hours afterwards. In contrast, in the RP group 81%
      had a reduction in VAS score within 3 hours. Using the new protocol there were no
      adverse events requiring intervention such as medication or readmission to an
      intensive care unit. CONCLUSIONS: This study shows that in post-cardiac surgery
      patients a significant reduction in VAS scores can be safely realized by a nurse
      driven protocol. Furthermore, a reduction in time to achieve an acceptable pain
      score (VAS < 4) was realized.

PMID- 22357784
TI  - Pilot testing of a self-care education intervention for patients with heart
      failure.
AB  - BACKGROUND: A key component of the structured approach to the management of
      chronic heart failure (CHF) is effective patient education. Patient education is
      a precursor to performing appropriate health-related behaviours that can decrease
      rehospitalizations. AIM: To pilot test an educational intervention and to
      determine the efficacy of a self-care manual combined with a DVD for patients
      with CHF. Outcomes of interest included heart failure-related knowledge and self
      care behaviours. METHODS: This pilot study enrolled a sample of 38 patients with
      CHF. A pre-test/post-test design was conducted to assess changes in knowledge and
      self-care abilities. Knowledge was assessed with the Dutch Heart Failure
      Knowledge Scale and self-care behaviours were assessed using the Self-Care of
      Heart Failure Index. RESULTS: Of the 38 participants 71% were male, 50% were aged
      between 65 and 74 years, and 31.6% had not completed Year 10 education. There was
      a statistically significantly difference in the pre- and post-test scores for
      knowledge (p < 0.0001). Self-care showed positive improvement between pre- and
      post-test scores; maintenance (p = 0.027), management (p < 0.0001) and confidence
      (p = 0.051). CONCLUSION: This pilot study has indicated that a patient-centred
      self-care manual combined with a DVD is beneficial and is associated with an
      improvement in patients' knowledge and self-care abilities. PRACTICE
      IMPLICATIONS: Healthcare professionals should utilize multimedia educational
      resources specifically designed to meet the learning needs of patients with CHF.

PMID- 22357785
TI  - The correlation between peri-operative hyperglycemia and mortality in cardiac
      surgery patients: a systematic review.
AB  - BACKGROUND: Hyperglycemia occurs frequently in patients undergoing cardiac
      surgery. It has been identified as a risk factor for increased peri-operative
      morbidity and mortality. AIM: To review the evidence of the correlation of peri
      operative hyperglycemia with mortality in cardiac surgery patients and to discuss
      the main results in order to provide evidence-based knowledge for the appropriate
      glycemic control. METHODS: We searched the electronic databases MEDLINE, CINAHL
      and EMBASE in June 2010. The material of our study was articles published between
      1 January 1990 and 31 May 2010, which investigated the correlation between peri
      operative hyperglycemia and in-hospital and/or 30-day cardiac surgery mortality.
      RESULTS: Out of the 16 reviewed articles in our study, 12 (75%) significantly
      associated hyperglycemia and inadequate blood glucose control with increased
      mortality. In addition, four of the reviewed articles were controlled randomized
      trials and among them only one demonstrated strong correlation between poor
      glycemic control and mortality. No study was multi-centre and the reviewed
      articles were characterized by different definitions of peri-operative
      hyperglycemia, different intensity and duration of the applied therapy and
      heterogeneity of the population. CONCLUSION: It is clear that peri-operative
      hyperglycemia is harmful for cardiac surgery patients. The significant shortage
      of randomized controlled trials, the absence of multicentre studies, the
      different definitions of peri-operative hyperglycemia, the different intensity
      and duration of the applied insulin therapy protocol and the heterogeneity of the
      studied population (diabetics and non-diabetics) are significant limitations,
      which could explain the inconsistent findings of the literature. These
      limitations indicate the need for further research.

PMID- 22357786
TI  - Work-related cardiovascular disease risk factors using a socioecological
      approach: implications for practice and research.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of mortality.
      Numerous investigations have linked occupational factors and CVD. Occupational
      factors such as overtime work have an enormous effect on the CVD risk of
      industrial workers. However, risk factors for CVD are not systematically reviewed
      in the workplace. The purpose of the paper is to review work-related risk factors
      for CVD. METHODS: A systematic review of work-related CVD risk factors was
      performed, yielding 180 articles. All articles were assessed in relation to
      inclusion and exclusion criteria, resulting in 44 articles being reviewed. The
      sole inclusion criteria was work-related environmental factors and intra/inter
      personal factors (psychosocial factors), which is based on the socioecological
      perspective. The articles were also assessed regarding the quality of each study
      using the scoring methods developed by Cesario et al. and Brown et al.
      CONCLUSION: The literature review demonstrated that work environment factors such
      as shift work, overtime work, and noise and chemical exposures; and psychosocial
      factors such as job stress, social support, and socioeconomic status cannot be
      explained or intervened by one single risk factor. Furthermore, certain
      occupational factors were shown to aggravate or attenuate other risk factors. The
      implication of these findings is to incorporate work-related environmental and
      psychosocial factors into assessment of the patient's CVD risks and intervention
      plan. Future research should also incorporate a well-defined conceptual framework
      to address the effects of work-related environmental and psychosocial factors on
      CVD among CVD patients.

PMID- 22357787
TI  - Content and distribution of discursive space in consultations between patients
      with atrial fibrillation and healthcare professionals.
AB  - AIM: To describe (i) the topics participants talk about, (ii) the use of
      discursive space in consultations between patients with atrial fibrillation (AF)
      and their nurses and physicians, and (iii) the frequencies of the ways the
      patients, nurses and physicians introduce the topics. METHODS: Data were
      collected from 23 videotaped consultations concerning patients with AF as well as
      physicians and nurses, respectively. To obtain a description of topics discussed,
      the transcripts were analysed using content analysis. The patterns of dominance
      for the respective topic and participant were explored from the framework of
      analysis that treats dominance. RESULTS: Four topics were used by both nurses and
      physicians in the consultations. These were 'pathophysiology', 'diagnostic
      procedures', 'treatment' and 'activity'. In the nurse-patient consultation an
      additional topic, 'routines related to the physician's responsibilities',
      emerged. With respect to the number of words and turns, the distribution of the
      discourse space was almost equal between the nurses and patients and unequal
      between the physicians and patients. The healthcare professionals initiated the
      topics more frequently compared to the patients, whereby the medical approach
      recommended in the guidelines for AF could be recognized. The patients were the
      dominating initiators in the topic 'activity', which refers to the adaptation of
      activities in daily life in relation to the AF. CONCLUSIONS: The medical-driven
      agenda dominates over the patient-driven agenda in consultations between
      healthcare professional and patients with AF. The patients initiated the
      conversations when discussing living with AF and were more talkative during
      conversations in nurse consultations.

PMID- 22357788
TI  - Being a close relative of a patient with a left ventricular assist device.
AB  - BACKGROUND: Every year in Sweden, between five and ten patients receive a
      mechanical heart pump due to grave heart failure. One such pump is the left
      ventricle assist device (LVAD). At home they need much support from their family.
      AIM: To investigate the close relatives' experience of their role in relation to
      patients with an LVAD. METHODS: An exploratory study using unstructured
      interviews with six close relatives of patients with an LVAD. The interviews
      consisted of one open question: 'What is it like to be the close relative of a
      patient with an LVAD?' The interviews were analysed using thematic content
      analysis. RESULTS: The time before LVAD surgery was described as a time of
      emotional ups and downs, and compared to 'being on an emotional rollercoaster
      ride'. The nearest relatives were in shock, felt anxiety and uncertainty, and
      wished to be near the patient. The time after surgery was described as a period
      in which they had to 'cope with the new situation.' During this period, the staff
      was experienced as a resource and the relatives described feelings of gratitude,
      willpower, and acceptance. The stay at home with a person with an LVAD was
      described as a 'new orientation phase' with limited freedom and the need for
      respite care. The interviewees expressed the need for support, especially once
      the patient was at home. CONCLUSION: It is important to also offer long-term
      professional support to the nearest relatives of patients with an LVAD.

PMID- 22357789
TI  - Electrical stimulation of retinal neurons in epiretinal and subretinal
      configuration using a multicapacitor array.
AB  - Electrical stimulation of retinal neurons offers the possibility of partial
      restoration of visual function. Challenges in neuroprosthetic applications are
      the long-term stability of the metal-based devices and the physiological
      activation of retinal circuitry. In this study, we demonstrate electrical
      stimulation of different classes of retinal neurons with a multicapacitor array.
      The array--insulated by an inert oxide--allows for safe stimulation with
      monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit
      retinas were interfaced in either epiretinal or subretinal configuration to the
      multicapacitor array. The evoked activity was recorded from ganglion cells that
      respond to light increments by an extracellular tungsten electrode. First, a
      monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a
      complex burst of action potentials in ganglion cells. The first action potential
      occurs within 1 ms and is attributed to direct stimulation. Within the next
      milliseconds additional spikes are evoked through bipolar cell or photoreceptor
      depolarization, as confirmed by pharmacological blockers. Second, monophasic
      epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells
      by hyperpolarization of photoreceptor terminals. These stimuli mimic the
      photoreceptor response to light increments. Third, the stimulation symmetry
      between current polarities (anodal/cathodal) and retina-array configuration
      (epi/sub) is confirmed in an experiment in which stimuli presented at different
      positions reveal the center-surround organization of the ganglion cell. A simple
      biophysical model that relies on voltage changes of cell terminals in the
      transretinal electric field above the stimulation capacitor explains our results.
      This study provides a comprehensive guide for efficient stimulation of different
      retinal neuronal classes with low-amplitude capacitive currents.

PMID- 22357791
TI  - Passive resting state and history of antagonist muscle activity shape active
      extensions in an insect limb.
AB  - Limb movements can be driven by muscle contractions, external forces, or
      intrinsic passive forces. For lightweight limbs like those of insects or small
      vertebrates, passive forces can be large enough to overcome the effects of
      gravity and may even generate limb movements in the absence of active muscle
      contractions. Understanding the sources and actions of such forces is therefore
      important in understanding motor control. We describe passive properties of the
      femur-tibia joint of the locust hind leg. The resting angle is determined
      primarily by passive properties of the relatively large extensor tibiae muscle
      and is influenced by the history of activation of the fast extensor tibiae motor
      neuron. The resting angle is therefore better described as a history-dependent
      resting state. We selectively stimulated different flexor tibiae motor neurons to
      generate a range of isometric contractions of the flexor tibiae muscle and then
      stimulated the fast extensor tibiae motor neuron to elicit active tibial
      extensions. Residual forces in the flexor muscle have only a small effect on
      subsequent active extensions, but the effect is larger for distal than for
      proximal flexor motor neurons and varies with the strength of flexor activation.
      We conclude that passive properties of a lightweight limb make substantial and
      complex contributions to the resting state of the limb that must be taken into
      account in the patterning of neuronal control signals driving its active
      movements. Low variability in the effects of the passive forces may permit the
      nervous system to accurately predict their contributions to behavior.

PMID- 22357792
TI  - Fast corrective responses are evoked by perturbations approaching the natural
      variability of posture and movement tasks.
AB  - A wealth of studies highlight the importance of rapid corrective responses during
      voluntary motor tasks. These studies used relatively large perturbations to evoke
      robust muscle activity. Thus it remains unknown whether these corrective
      responses (latency 20-100 ms) are evoked at perturbation levels approaching the
      inherent variability of voluntary control. To fill this gap, we examined
      responses for large to small perturbations applied while participants either
      performed postural or reaching tasks. To address multijoint corrective responses,
      we induced various amounts of single-joint elbow motion with scaled amounts of
      combined elbow and shoulder torques. Indeed, such perturbations are known to
      elicit a response at the unstretched shoulder muscle, which reflects an internal
      model of arm intersegmental dynamics. Significant muscle responses were observed
      during both postural control and reaching, even when perturbation-related joint
      angle, velocity, and acceleration overlapped in distribution with deviations
      encountered in unperturbed trials. The response onsets were consistent across the
      explored range of perturbation loads, with short-latency onset for the muscles
      spanning the elbow joints (20-40 ms), and long-latency for shoulder muscles
      (onset > 45 ms). In addition, the evoked activity was strongly modulated by
      perturbation magnitude. These results suggest that multijoint responses are not
      specifically engaged to counter motor errors that exceed a certain threshold.
      Instead, we suggest that these corrective processes operate continuously during
      voluntary motor control.

PMID- 22357790
TI  - Event-related potentials elicited by errors during the stop-signal task. II:
      human effector-specific error responses.
AB  - Although previous research with human and nonhuman primates has examined the
      neural correlates of performance monitoring, discrepancies in methodology have
      limited our ability to make cross-species generalizations. One major obstacle
      arises from the use of different behavioral responses and tasks across different
      primate species. Specifically, it is unknown whether performance-monitoring
      mechanisms rely on different neural circuitry in tasks requiring oculomotor vs.
      skeletomotor responses. Here, we show that the human error-related negativity
      (ERN) elicited by a saccadic eye-movement response relative to a manual response
      differs in several critical ways. The human saccadic ERN exhibits a prolonged
      duration, a broader frontomedial voltage distribution, and different neural
      source estimates than the manual ERN in exactly the same stop-signal task. The
      human saccadic error positivity (Pe) exhibited a frontomedial voltage
      distribution with estimated electrical sources in supplementary motor area and
      rostral anterior cingulate cortex for saccadic responses, whereas the manual Pe
      showed a posterior scalp distribution and potential origins in the superior
      parietal lobule. These findings constrain models of the cognitive mechanisms
      indexed by the ERN/Pe complex. Moreover, by paralleling work with nonhuman
      primates performing the same saccadic stop-signal task (Godlove et al. 2011), we
      demonstrate a cross-species homology of error event-related potentials (ERPs) and
      lay the groundwork for definitively localizing the neural sources of performance
      monitoring ERPs.

PMID- 22357794
TI  - Distinct developmental profiles in typical speech acquisition.
AB  - Three- to five-year-old children produce speech that is characterized by a high
      level of variability within and across individuals. This variability, which is
      manifest in speech movements, acoustics, and overt behaviors, can be input to
      subgroup discovery methods to identify cohesive subgroups of speakers or to
      reveal distinct developmental pathways or profiles. This investigation
      characterized three distinct groups of typically developing children and provided
      normative benchmarks for speech development. These speech development profiles,
      identified among 63 typically developing preschool-aged speakers (ages 36-59 mo),
      were derived from the children's performance on multiple measures. These profiles
      were obtained by submitting to a k-means cluster analysis of 72 measures that
      composed three levels of speech analysis: behavioral (e.g., task accuracy,
      percentage of consonants correct), acoustic (e.g., syllable duration, syllable
      stress), and kinematic (e.g., variability of movements of the upper lip, lower
      lip, and jaw). Two of the discovered group profiles were distinguished by
      measures of variability but not by phonemic accuracy; the third group of children
      was characterized by their relatively low phonemic accuracy but not by an
      increase in measures of variability. Analyses revealed that of the original 72
      measures, 8 key measures were sufficient to best distinguish the 3 profile
      groups.

PMID- 22357793
TI  - Exercise training normalizes an increased neuronal excitability of NTS-projecting
      neurons of the hypothalamic paraventricular nucleus in hypertensive rats.
AB  - Elevated sympathetic outflow and altered autonomic reflexes, including impaired
      baroreflex function, are common findings observed in hypertensive disorders.
      Although a growing body of evidence supports a contribution of preautonomic
      neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic
      control during hypertension, the precise underlying mechanisms remain unknown.
      Here, we aimed to determine whether the intrinsic excitability and repetitive
      firing properties of preautonomic PVN neurons that innervate the nucleus tractus
      solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats
      (SHR). Moreover, given that exercise training is known to improve and/or correct
      autonomic deficits in hypertensive conditions, we evaluated whether exercise is
      an efficient behavioral approach to correct altered neuronal excitability in
      hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled
      PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained
      (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased
      excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input
      output function in response to depolarizing stimuli, a hyperpolarizing shift in
      Na(+) spike threshold, and smaller hyperpolarizing afterpotentials. Importantly,
      we found exercise training in SHR rats to restore all these parameters back to
      those levels observed in WKY-S rats. In several cases, exercise evoked opposing
      effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects
      on PVN-NTS neurons are state dependent. Taken together, our results suggest that
      elevated preautonomic PVN-NTS neuronal excitability may contribute to altered
      autonomic control in SHR rats and that exercise training efficiently corrects
      these abnormalities.

PMID- 22357795
TI  - Physiological and molecular characterization of connexin hemichannels in
      zebrafish retinal horizontal cells.
AB  - Connexin channels mediate electrical synaptic transmission when assembled as cell
      to-cell pores at gap junctions and can mediate transmembrane currents when
      expressed in plasma membranes as hemichannels. They are widely expressed in the
      vertebrate retina where in electrical synapses they are critical for transmission
      of visual signals. While the roles of connexins in electrical synapses are well
      studied, the function and roles of connexin hemichannels in the nervous system
      are less well understood. Genetic deletion in zebrafish of connexin (Cx) 55.5
      alters horizontal cell feedback to cones, spectral responses, and visual
      behavior. Here, we have characterized the properties of hemichannel currents in
      zebrafish retinal horizontal cells and examined the roles of two connexin
      isoforms, Cx55.5 and Cx52.6, that are coexpressed in these cells. We report that
      zebrafish horizontal cells express hemichannel currents that conduct inward
      current at physiological negative potentials and Ca(2+) levels. Manipulation of
      Cx55.5 and Cx52.6 gene expression in horizontal cells of adult zebrafish revealed
      that both Cx55.5 and Cx52.6 contribute to hemichannel currents; however, Cx55.5
      expression is necessary for high-amplitude currents. Similarly, coexpression of
      Cx55.5 with Cx52.6 in oocytes increased hemichannel currents in a supra-additive
      manner. Taken together these results demonstrate that zebrafish horizontal cell
      hemichannel currents exhibit the functional characteristics necessary to
      contribute to synaptic feedback at the first visual synapse, that both Cx55.5 and
      Cx52.6 contribute to hemichannel currents, and that Cx55.5 may have an additional
      regulatory function enhancing the amplitude of hemichannel currents.

PMID- 22357796
TI  - Impaired crossed facilitation of the corticospinal pathway after cervical spinal
      cord injury.
AB  - In uninjured humans, it is well established that voluntary contraction of muscles
      on one side of the body can facilitate transmission in the contralateral
      corticospinal pathway. This crossed facilitatory effect may favor interlimb
      coordination and motor performance. Whether this aspect of corticospinal function
      is preserved after chronic spinal cord injury (SCI) is unknown. Here, using
      transcranial magnetic stimulation, we show in patients with chronic cervical SCI
      (C(5)-C(8)) that the size of motor evoked potentials (MEPs) in a resting
      intrinsic hand muscle remained unchanged during increasing levels of voluntary
      contraction with a contralateral distal or proximal arm muscle. In contrast, MEP
      size in a resting hand muscle was increased during the same motor tasks in
      healthy control subjects. The magnitude of voluntary electromyography was
      negatively correlated with MEP size after chronic cervical SCI and positively
      correlated in healthy control subjects. To examine the mechanisms contributing to
      MEP crossed facilitation we examined short-interval intracortical inhibition
      (SICI), interhemispheric inhibition (IHI), and motoneuronal behavior by testing F
      waves and cervicomedullary MEPs (CMEPs). During strong voluntary contractions
      SICI was unchanged after cervical SCI and decreased in healthy control subjects
      compared with rest. F-wave amplitude and persistence and CMEP size remained
      unchanged after cervical SCI and increased in healthy control subjects compared
      with rest. In addition, during strong voluntary contractions IHI was unchanged in
      cervical SCI compared with rest. Our results indicate that GABAergic
      intracortical circuits, interhemispheric glutamatergic projections between motor
      cortices, and excitability of index finger motoneurons are neural mechanisms
      underlying, at least in part, the lack of crossed corticospinal facilitation
      observed after SCI. Our data point to the spinal motoneurons as a critical site
      for modulating corticospinal transmission after chronic cervical SCI.

PMID- 22357799
TI  - Use of a goal setting intervention to increase adherence to low back pain
      rehabilitation: a randomized controlled trial.
AB  - OBJECTIVE: To examine the effects of a goal setting intervention on self
      efficacy, treatment efficacy, adherence and treatment outcome in patients
      undergoing low back pain rehabilitation. DESIGN: A mixed-model 2 (time) * 3
      (group) randomized controlled trial. SETTING: A residential rehabilitation centre
      for military personnel. SUBJECTS: UK military personnel volunteers (N = 48); mean
      age was 32.9 (SD 7.9) with a diagnosis of non-specific low back pain.
      INTERVENTIONS: Subjects were randomly assigned to either a goal setting
      experimental group (Exp, n = 16), therapist-led exercise therapy group (C1, n =
      16) or non-therapist-led exercise therapy group (C2, n = 16). Treatment duration
      for all groups was three weeks. MAIN MEASURES: Self-efficacy, treatment efficacy
      and treatment outcome were recorded before and after the treatment period.
      Adherence was rated during regularly scheduled treatment sessions using the
      Sports Injury Rehabilitation Adherence Scale (SIRAS). The Biering-Sorensen test
      was used as the primary measure of treatment outcome. RESULTS: ANCOVA results
      showed that adherence scores were significantly higher in the experimental group
      (13.70 +/- 1.58) compared with C2 (11.74 +/- 1.35), (P < 0.025). There was no
      significant difference for adherence between the experimental group and C1 (P =
      0.13). Self-efficacy was significantly higher in the experimental group compared
      to both C1 and C2 (P < 0.05), whereas no significant difference was found for
      treatment efficacy. Treatment outcome did not differ significantly between the
      experimental and two control groups. CONCLUSIONS: The findings provide partial
      support for the use of goal setting to enhance adherence in clinical
      rehabilitation.

PMID- 22357800
TI  - Patient characteristics of provider survey respondents: no evidence of
      nonresponse bias.
AB  - Surveys of physicians are an important tool to assess opinions and self-reported
      behaviors of this policy-relevant population. However, this population is
      notoriously difficult to survey and plagued with low and falling response rates.
      In order to evaluate the potential import of response rate, we examine the
      presence of nonresponse bias in a survey of physicians providing diabetes care
      that achieved a 36% response rate. Unlike other studies examining differences in
      individual characteristics for responding and nonresponding physicians, we also
      assess differences with respect to aggregate patient demographic, clinical, and
      behavioral characteristics. We are unable to demonstrate nonresponse bias, even
      with what could be construed as a relative low response rate. Nonetheless as the
      threat of nonresponse bias can never be completely assuaged, we believe that it
      should be monitored as a matter of course in physician surveys and offer a new
      dimension by which it can be evaluated.

PMID- 22357798
TI  - Nicotinic neuromodulation in auditory cortex requires MAPK activation in
      thalamocortical and intracortical circuits.
AB  - Activation of nicotinic acetylcholine receptors (nAChRs) by systemic nicotine
      enhances sensory-cognitive function and sensory-evoked cortical responses.
      Although nAChRs mediate fast neurotransmission at many synapses in the nervous
      system, nicotinic regulation of cortical processing is neuromodulatory. To
      explore potential mechanisms of nicotinic neuromodulation, we examined whether
      intracellular signal transduction involving mitogen-activated protein kinase
      (MAPK) contributes to regulation of tone-evoked responses in primary auditory
      cortex (A1) in the mouse. Systemic nicotine enhanced characteristic frequency
      (CF) tone-evoked current-source density (CSD) profiles in A1, including the
      shortest-latency (presumed thalamocortical) current sink in layer 4 and longer
      latency (presumed intracortical) sinks in layers 2-4, by increasing response
      amplitudes and decreasing response latencies. Microinjection of the MAPK kinase
      (MEK) inhibitor U0126 into the thalamus, targeting the auditory thalamocortical
      pathway, blocked the effect of nicotine on the initial (thalamocortical) CSD
      component but did not block enhancement of longer-latency (intracortical)
      responses. Conversely, microinjection of U0126 into supragranular layers of A1
      blocked nicotine's effect on intracortical, but not thalamocortical, CSD
      components. Simultaneously with enhancement of CF-evoked responses, responses to
      spectrally distant (nonCF) stimuli were reduced, implying nicotinic "sharpening"
      of frequency receptive fields, an effect also blocked by MEK inhibition.
      Consistent with these physiological results, acoustic stimulation with nicotine
      produced immunolabel for activated MAPK in A1, primarily in layer 2/3 cell
      bodies. Immunolabel was blocked by intracortical microinjection of the nAChR
      antagonist dihydro-beta-erythroidine, but not methyllycaconitine, implicating
      alpha4beta2*, but not alpha7, nAChRs. Thus activation of MAPK in functionally
      distinct forebrain circuits--thalamocortical, local intracortical, and long-range
      intracortical--underlies nicotinic neuromodulation of A1.

PMID- 22357801
TI  - Activity of ceftaroline against serotyped Streptococcus pneumoniae isolates from
      Europe and South Africa associated with community-acquired bacterial pneumonia
      (2007-08).
AB  - OBJECTIVES: To determine the activity of ceftaroline (the active metabolite of
      the prodrug ceftaroline fosamil), a new cephalosporin recently approved in the
      USA for the treatment of community-acquired bacterial pneumonia, against
      serotyped Streptococcus pneumoniae causing community-acquired bacterial pneumonia
      from Europe and South Africa. METHODS: During 2007-08, 74 centres submitted 857
      isolates of S. pneumoniae from patients with community-acquired bacterial
      pneumonia. These were re-identified and serotyped. MICs of ceftaroline and 12
      comparators were determined by CLSI broth microdilution at a central laboratory.
      RESULTS: Ceftaroline was very active against all 857 S. pneumoniae isolates
      (MIC(90) 0.12 mg/L). The MIC(50) for South African isolates was 0.06 mg/L
      compared with 0.004 or 0.008 mg/L for isolates from elsewhere. Antibiotic
      resistance was also higher in South Africa than other countries. Serotypes 3, 1,
      7 and 11 were more susceptible to ceftaroline (MIC(90) = 0.008 mg/L) and the
      reference antibiotics than the population as a whole. Ceftaroline showed a
      biphasic MIC distribution (associated with cefuroxime susceptibility), the extent
      of which differed between isolate populations. Nevertheless, the highest
      ceftaroline MIC observed was only 0.5 mg/L (two isolates: one from the UK and one
      from South Africa). CONCLUSIONS: These data from a large collection of S.
      pneumoniae isolates during 2007-08 from Europe and South Africa with varying
      serotype and antibiotic susceptibility, confirm the excellent in vitro activity
      of ceftaroline against S. pneumoniae causing community-acquired bacterial
      pneumonia in both adults and children.

PMID- 22357802
TI  - Etravirine concentrations in CSF in HIV-infected patients.
AB  - OBJECTIVES: To determine etravirine concentrations in CSF in HIV-infected
      patients. METHODS: Twelve HIV-1 adult antiretroviral-experienced patients
      receiving an etravirine-containing regimen for at least 1 month were enrolled.
      Both CSF and blood samples were taken around 12 h after the last etravirine dose.
      Liquid chromatography-tandem mass spectrometry was used to determine etravirine
      concentrations, and HIV-1 viral load was determined by real-time PCR (limit of
      detection 40 copies/mL). RESULTS: Twelve blood and 12 CSF samples were collected.
      The median CD4 count was 333 (84-765) cells/mm(3) and the median plasma HIV-1
      viral load was <40 (range <40-1777) copies/mL. The median time on etravirine was
      34 (range 4-140) weeks. The median etravirine concentration in plasma was 611.5
      (range 148-991) ng/mL. The median CSF etravirine concentration was 7.24 (range
      3.59-17.9) ng/mL; in all cases, values were above the IC(50) range (0.39-2.4
      ng/mL). The median etravirine CSF:plasma ratio was 0.01 (range 0.005-0.03). The
      CSF viral load was >40 copies/mL in one patient and plasma viral load was still
      detectable after 4 weeks of therapy. CONCLUSIONS: Etravirine achieves
      concentrations several times greater than the IC(50) range in CSF. All patients
      with undetectable plasma viral load were virologically suppressed in CSF while
      receiving an etravirine-containing regimen. Etravirine may help in controlling
      HIV-1 in CNS.

PMID- 22357797
TI  - Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons.
AB  - Adenosine has been proposed as an endogenous homeostatic sleep factor that
      accumulates during waking and inhibits wake-active neurons to promote sleep. It
      has been specifically hypothesized that adenosine decreases wakefulness and
      promotes sleep recovery by directly inhibiting wake-active neurons of the basal
      forebrain (BF), particularly BF cholinergic neurons. We previously showed that
      adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how
      adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how
      adenosine uptake and adenosine metabolism are involved in regulating
      extracellular levels of adenosine. Our experiments were conducted using whole
      cell patch-clamp recordings in mouse brain slices. We found that in BF
      cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked
      glutamatergic excitatory postsynaptic currents (EPSCs) and decreased the
      frequency of spontaneous and miniature EPSCs through presynaptic A(1) receptors.
      Thus we have demonstrated that in addition to directly inhibiting BF cholinergic
      neurons, adenosine depresses excitatory inputs to these neurons. It is therefore
      possible that both direct and indirect inhibition may synergistically contribute
      to the sleep-promoting effects of adenosine in the BF. We also found that
      blocking the influx of adenosine through the equilibrative nucleoside
      transporters or inhibiting adenosine kinase and adenosine deaminase increased
      endogenous adenosine inhibitory tone, suggesting a possible mechanism through
      which adenosine extracellular levels in the basal forebrain are regulated.

PMID- 22357803
TI  - Use of therapeutic drug monitoring to treat Elizabethkingia meningoseptica
      meningitis and bacteraemia in an adult.

PMID- 22357804
TI  - gyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin
      in clinical isolates of Mycobacterium tuberculosis.
AB  - OBJECTIVES: To compare mutations in the quinolone resistance-determining region
      of the gyrA gene and flanking sequences with the MICs of ofloxacin and
      moxifloxacin for Mycobacterium tuberculosis. METHODS: The presence of mutations
      in 177 drug-resistant M. tuberculosis isolates was determined by DNA sequencing
      and the MICs quantified by MGIT 960. RESULTS: Single nucleotide polymorphisms
      were detected at codons 94 (n = 30), 90 (n = 12), 91 (n = 3), 89 (n = 1), 88 (n =
      1) and 80 (n = 1). Four isolates with double mutations D94G plus A90V (n = 2) and
      D94G plus D94N (n = 2) reflect mixed populations. Agreement between genotypic and
      phenotypic susceptibility was high (>=97%) for both drugs. Mutant isolates had an
      MIC(50) of 8.0 mg/L and an MIC(90) of >10 mg/L for ofloxacin compared with an
      MIC(50) and MIC(90) of 2.0 mg/L for moxifloxacin. Codons 94 and 88 were linked to
      higher levels of fluoroquinolone resistance compared with codons 90, 91 and 89.
      The MIC distributions for the wild-type isolates ranged from <=0.5 to 2.0 mg/L
      for ofloxacin and from <=0.125 to 0.25 mg/L for moxifloxacin. However, 96% of the
      isolates with genetic alterations had MICs <=2.0 mg/L for moxifloxacin, which is
      within its achievable serum levels. CONCLUSIONS: This study provides quantitative
      evidence that the addition of moxifloxacin to extensively drug-resistant
      tuberculosis (XDR-TB) regimens based on a clinical breakpoint of 2.0 mg/L has
      merit. The use of moxifloxacin in the treatment of multidrug-resistant
      tuberculosis may prevent the acquisition of additional mutations and development
      of XDR-TB.

PMID- 22357805
TI  - Social determinants of health: the role of neighbourhoods, psychological factors
      and health behaviours in predicting health outcomes for the urban poor in India.
AB  - The aim of this study was to investigate the role of neighbourhoods,
      psychological characteristics and health behaviours on actual health outcomes and
      perceived health for a lower income urban Indian sample. A cross-sectional design
      was used with a community sample of 491 adults in two neighbourhoods.
      Neighbourhood and perceived stress played a role in predicitng risk of chronic
      conditions as well as perceived health. Positive emotional style was associated
      with decreased perception of poor health. Results support the importance of
      combining contextual as well as individual level characteristics in understanding
      health outcomes.

PMID- 22357806
TI  - Control of cardiovascular variability during undisturbed wake-sleep behavior in
      hypocretin-deficient mice.
AB  - The central neural mechanisms underlying differences in cardiovascular
      variability between wakefulness, non-rapid-eye-movement sleep (NREMS), and rapid
      eye-movement sleep (REMS) remain poorly understood. These mechanisms may involve
      hypocretin (HCRT)/orexin signaling. HCRT signaling is linked to wake-sleep
      states, involved in central autonomic control, and impaired in narcoleptic
      patients. Thus, we investigated whether HCRT signaling plays a role in
      controlling cardiovascular variability during spontaneous behavior in HCRT
      deficient mice. HCRT-ataxin3 transgenic mice lacking HCRT neurons (TG), knockout
      mice lacking HCRT peptides (KO), and wild-type controls (WT) were instrumented
      with electrodes for sleep recordings and a telemetric blood pressure transducer.
      Fluctuations of systolic blood pressure (SBP) and heart period (HP) during
      undisturbed wake-sleep behavior were analyzed with the sequence technique, cross
      correlation functions, and coherent averaging of SBP surges. During NREMS, all
      mice had lower SBP variability, greater baroreflex contribution to HP control at
      low frequencies, and greater amplitude of the central autonomic and baroreflex
      changes in HP associated with SBP surges than during wakefulness. During REMS,
      all mice had higher SBP variability and depressed central autonomic and
      baroreflex HP controls relative to NREMS. HP variability during REMS was higher
      than during NREMS in WT only. TG and KO also had lower amplitude of the cardiac
      baroreflex response to SBP surges during REMS than WT. These results indicate
      that chronic lack of HCRT signaling may cause subtle alterations in the control
      of HP during spontaneous behavior. Conversely, the integrity of HCRT signaling is
      not necessary for the occurrence of physiological sleep-dependent changes in SBP
      variability.

PMID- 22357807
TI  - Influence of acetaminophen consumption and exercise on Achilles tendon structural
      properties in male Wistar rats.
AB  - Chronic consumption of acetaminophen (APAP) during exercise training leads to a
      reduction in tendon stiffness and modulus compared with a placebo. We explored
      whether this effect could be due to a reduction in tendon collagen content or
      cross-linking. Ten-week-old male Wistar rats (n = 50) were divided into placebo
      or APAP groups and into sedentary or treadmill-exercised groups. APAP (200 mg/kg)
      or saline was administered once daily by oral gavage. Rats in the exercise groups
      ran on a treadmill 5 days per week for 8 wk with progression to 60 min per day,
      20 m/min, and 8 degrees  incline. After 8 wk, lyophilized Achilles tendon samples
      were assayed for the collagen-specific amino acid hydroxyproline and cross
      linking [hydroxylyslpyridinoline (HP)] content by high-performance liquid
      chromatrography. Collagen content was not influenced by exercise or APAP (P >
      0.05). Compared with placebo, tendon water content was 7% (P = 0.006, main
      effect) lower in animals consuming APAP (placebo: 54.79 +/- 0.8%, APAP: 50.89 +/-
      1.2%). HP in the Achilles tendon was 36% greater (sedentary: 141 +/- 15,
      exercise: 204 +/- 26 mmol/mol collagen) in the exercise-trained rats independent
      of drug treatment (P = 0.020, main effect). Independent of exercise, HP content
      was 33% lower (P = 0.032, main effect) in the animals consuming APAP (placebo:
      195 +/- 21, APAP: 140 +/- 19 mmol/mol collagen). Our data suggests that chronic
      consumption of APAP results in a reduction in collagen cross-linking and a loss
      of tissue water independent of chronic exercise. This reduction in cross-linking
      and water content could contribute to the decrease in tendon stiffness noted in
      humans chronically consuming APAP.

PMID- 22357808
TI  - Photo quiz. Hyperkeratotic scales over the scalp.

PMID- 22357810
TI  - Least among equals.

PMID- 22357812
TI  - US asks journals to censor bird flu studies.

PMID- 22357809
TI  - A review of the virological efficacy of the 4 World Health Organization
      recommended tenofovir-containing regimens for initial HIV therapy.
AB  - We systematically reviewed studies of the virological efficacy of the 4 new
      tenofovir (TDF)-containing regimens recommended for initial antiretroviral (ARV)
      therapy in the 2010 World Health Organization ARV Treatment Guidelines. Thirty
      three studies assessed the efficacy of 1 or more TDF-containing regimens:
      TDF/lamivudine (3TC)/nevirapine (NVP) (n = 3), TDF/ emtricitabine (FTC)/NVP (n =
      9), TDF/3TC/efavirenz (EFV) (n = 6), and TDF/FTC/EFV (n = 19). TDF/3TC/NVP was
      the least well-studied and appeared the least efficacious of the 4 regimens. In 2
      comparative studies, TDF/3TC/NVP was associated with significantly more
      virological failure than AZT/3TC/NVP; a third study was terminated prematurely
      because of early virological failure. TDF/FTC/NVP was either equivalent or
      inferior to its comparator arms. TDF/3TC/EFV was equivalent to its comparator
      arms. TDF/FTC/EFV was equivalent or superior to its comparator arms. Possible
      explanations for these findings include the greater antiviral activity of EFV
      versus NVP and longer intracellular half-life of FTC-triphosphate versus 3TC
      triphosphate. Further study of TDF/3TC/NVP is required before it is widely
      deployed for initial ARV therapy.

PMID- 22357820
TI  - The cover. Mrs Douse, chieftainess of Kitwancool.

PMID- 22357821
TI  - Smuggled wildlife products seized at US airports harbor zoonotic viruses.

PMID- 22357822
TI  - Patient-centered medical homes offer a model for better, cheaper health care.

PMID- 22357823
TI  - Collaborative effort targets 17 tropical diseases for control, elimination.

PMID- 22357824
TI  - Physician billing and cardiac stress testing patterns.

PMID- 22357825
TI  - Physician billing and cardiac stress testing patterns.

PMID- 22357826
TI  - Neuron number in children with autism.

PMID- 22357827
TI  - Marketing pharmaceuticals: a constitutional right to sell prescriber-identified
      data?

PMID- 22357828
TI  - Veterans and the Affordable Care Act.

PMID- 22357829
TI  - Do physicians need a "shopping cart" for health care services?

PMID- 22357830
TI  - A piece of my mind. Putting the "art" in "crash cart".

PMID- 22357831
TI  - Cost-effectiveness of adult vaccination strategies using pneumococcal conjugate
      vaccine compared with pneumococcal polysaccharide vaccine.
AB  - CONTEXT: The cost-effectiveness of 13-valent pneumococcal conjugate vaccine
      (PCV13) compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23)
      among US adults is unclear. OBJECTIVE: To estimate the cost-effectiveness of
      PCV13 vaccination strategies in adults. DESIGN, SETTING, AND PARTICIPANTS: A
      Markov state-transition model, lifetime time horizon, societal perspective.
      Simulations were performed in hypothetical cohorts of US 50-year-olds.
      Vaccination strategies and effectiveness estimates were developed by a Delphi
      expert panel; indirect (herd immunity) effects resulting from childhood PCV13
      vaccination were extrapolated based on observed PCV7 effects. Data sources for
      model parameters included Centers for Disease Control and Prevention Active
      Bacterial Core surveillance, National Hospital Discharge Survey and Nationwide
      Inpatient Sample data, and the National Health Interview Survey. MAIN OUTCOME
      MEASURES: Pneumococcal disease cases prevented and incremental costs per quality
      adjusted life-year (QALY) gained. RESULTS: In the base case scenario,
      administration of PCV13 as a substitute for PPSV23 in current recommendations
      (ie, vaccination at age 65 years and at younger ages if comorbidities are
      present) cost $28,900 per QALY gained compared with no vaccination and was more
      cost-effective than the currently recommended PPSV23 strategy. Routine PCV13 at
      ages 50 and 65 years cost $45,100 per QALY compared with PCV13 substituted in
      current recommendations. Adding PPSV23 at age 75 years to PCV13 at ages 50 and 65
      years gained 0.00002 QALYs, costing $496,000 per QALY gained. Results were robust
      in sensitivity analyses and alternative scenarios, except when low PCV13
      effectiveness against nonbacteremic pneumococcal pneumonia was assumed or when
      greater childhood vaccination indirect effects were modeled. In these cases,
      PPSV23 as currently recommended was favored. CONCLUSION: Overall, PCV13
      vaccination was favored compared with PPSV23, but the analysis was sensitive to
      assumptions about PCV13 effectiveness against nonbacteremic pneumococcal
      pneumonia and the magnitude of potential indirect effects from childhood PCV13 on
      pneumococcal serotype distribution.

PMID- 22357832
TI  - Association of age and sex with myocardial infarction symptom presentation and in
      hospital mortality.
AB  - CONTEXT: Women are generally older than men at hospitalization for myocardial
      infarction (MI) and also present less frequently with chest pain/discomfort.
      However, few studies have taken age into account when examining sex differences
      in clinical presentation and mortality. OBJECTIVE: To examine the relationship
      between sex and symptom presentation and between sex, symptom presentation, and
      hospital mortality, before and after accounting for age in patients hospitalized
      with MI. DESIGN, SETTING, AND PATIENTS: Observational study from the National
      Registry of Myocardial Infarction, 1994-2006, of 1,143,513 registry patients
      (481,581 women and 661,932 men). MAIN OUTCOME MEASURES: We examined predictors of
      MI presentation without chest pain and the relationship between age, sex, and
      hospital mortality. RESULTS: The proportion of MI patients who presented without
      chest pain was significantly higher for women than men (42.0% [95% CI, 41.8%
      42.1%] vs 30.7% [95% CI, 30.6%-30.8%]; P < .001). There was a significant
      interaction between age and sex with chest pain at presentation, with a larger
      sex difference in younger than older patients, which became attenuated with
      advancing age. Multivariable adjusted age-specific odds ratios (ORs) for lack of
      chest pain for women (referent, men) were younger than 45 years, 1.30 (95% CI,
      1.23-1.36); 45 to 54 years, 1.26 (95% CI, 1.22-1.30); 55 to 64 years, 1.24 (95%
      CI, 1.21-1.27); 65 to 74 years, 1.13 (95% CI, 1.11-1.15); and 75 years or older,
      1.03 (95% CI, 1.02-1.04). Two-way interaction (sex and age) on MI presentation
      without chest pain was significant (P < .001). The in-hospital mortality rate was
      14.6% for women and 10.3% for men. Younger women presenting without chest pain
      had greater hospital mortality than younger men without chest pain, and these sex
      differences decreased or even reversed with advancing age, with adjusted OR for
      age younger than 45 years, 1.18 (95% CI, 1.00-1.39); 45 to 54 years, 1.13 (95%
      CI, 1.02-1.26); 55 to 64 years, 1.02 (95% CI, 0.96-1.09); 65 to 74 years, 0.91
      (95% CI, 0.88-0.95); and 75 years or older, 0.81 (95% CI, 0.79-0.83). The 3-way
      interaction (sex, age, and chest pain) on mortality was significant (P < .001).
      CONCLUSION: In this registry of patients hospitalized with MI, women were more
      likely than men to present without chest pain and had higher mortality than men
      within the same age group, but sex differences in clinical presentation without
      chest pain and in mortality were attenuated with increasing age.

PMID- 22357833
TI  - Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus,
      acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.
AB  - CONTEXT: Vaccination with whole-cell pertussis vaccine carries an increased risk
      of febrile seizures, but whether this risk applies to the acellular pertussis
      vaccine is not known. In Denmark, acellular pertussis vaccine has been included
      in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated
      poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September
      2002. OBJECTIVE: To estimate the risk of febrile seizures and epilepsy after DTaP
      IPV-Hib vaccination given at 3, 5, and 12 months. DESIGN, SETTING, AND
      PARTICIPANTS: A population-based cohort study of 378,834 children who were born
      in Denmark between January 1, 2003, and December 31, 2008, and followed up
      through December 31, 2009; and a self-controlled case series (SCCS) study based
      on children with febrile seizures during follow-up of the cohort. MAIN OUTCOME
      MEASURES: Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4
      7 days) after each vaccination and HR of epilepsy after first vaccination in the
      cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3,
      and 4-7 days) after each vaccination in the SCCS study. RESULTS: A total of 7811
      children were diagnosed with febrile seizures before 18 months, of whom 17 were
      diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000
      person-days), 32 children after the second (1.3 per 100,000 person-days), and 201
      children after the third (8.5 per 100,000 person-days) vaccinations. Overall,
      children did not have higher risks of febrile seizures during the 0 to 7 days
      after the 3 vaccinations vs a reference cohort of children who were not within 0
      to 7 days of vaccination. However, a higher risk of febrile seizures was found on
      the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second
      (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR,
      1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9
      children were diagnosed with febrile seizures after the first (5.5 per 100,000
      person-days), 12 children after the second (5.7 per 100,000 person-days), and 27
      children after the third (13.1 per 100,000 person-days) vaccinations. The
      relative incidences from the SCCS study design were similar to the cohort study
      design. Within 7 years of follow-up, 131 unvaccinated children and 2117
      vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15
      months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000
      person-years). After vaccination, children had a lower risk of epilepsy between 3
      and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later
      in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children. CONCLUSIONS: DTaP
      IPV-Hib vaccination was associated with an increased risk of febrile seizures on
      the day of the first 2 vaccinations given at 3 and 5 months, although the
      absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an
      increased risk of epilepsy.

PMID- 22357834
TI  - Does this patient with liver disease have cirrhosis?
AB  - CONTEXT: Among adult patients with liver disease, the ability to identify those
      most likely to have cirrhosis noninvasively is challenging. OBJECTIVE: To
      identify simple clinical indicators that can exclude or detect cirrhosis in
      adults with known or suspected liver disease. DATA SOURCES: We searched MEDLINE
      and EMBASE (1966 to December 2011) and reference lists from retrieved articles,
      previous reviews, and physical examination textbooks. STUDY SELECTION: We
      retained 86 studies of adequate quality that evaluated the accuracy of clinical
      findings for identifying histologically proven cirrhosis. DATA EXTRACTION: Two
      authors independently abstracted data (sensitivity, specificity, and likelihood
      ratios [LRs]) and assessed methodological quality. Random-effects meta-analyses
      were used to calculate summary LRs across studies. RESULTS: Among the 86 studies,
      19,533 patients were included in this meta-analysis, among whom 4725 had biopsy
      proven cirrhosis (prevalence rate, 24%; 95% CI, 20%-28%). Many physical
      examination and simple laboratory tests increase the likelihood of cirrhosis,
      though the presence of ascites (LR, 7.2; 95% CI, 2.9-12), a platelet count <160 x
      10(3)/MUL (LR, 6.3; 95% CI, 4.3-8.3), spider nevi (LR, 4.3; 95% CI 2.4-6.2), or a
      combination of simple laboratory tests with the Bonacini cirrhosis discriminant
      score >7 (LR, 9.4; 95% CI, 2.6-37) are the most frequently studied, reliable, and
      informative results. For lowering the likelihood of cirrhosis, the most useful
      findings are a Lok index <0.2 (a score created from the platelet count, serum
      aspartate aminotransferase and alanine aminotransferase, and prothrombin
      international normalized ratio; LR, 0.09; 95% CI, 0.03-0.31); a platelet count
      >=160 x 10(3)/MUL (LR, 0.29; 95% CI, 0.20-0.39); or the absence of hepatomegaly
      (LR, 0.37; 95% CI, 0.24-0.51). The overall impression of the clinician was not as
      informative as the individual findings or laboratory combinations. CONCLUSIONS:
      For identifying cirrhosis, the presence of a variety of clinical findings or
      abnormalities in a combination of simple laboratory tests that reflect the
      underlying pathophysiology increase its likelihood. To exclude cirrhosis,
      combinations of normal laboratory findings are most useful.

PMID- 22357835
TI  - Patient with a rash, abdominal pain, and weight loss.

PMID- 22357836
TI  - Prevention of pneumococcal infection with vaccines: an evolving story.

PMID- 22357839
TI  - JAMA patient page. Cirrhosis.

PMID- 22357841
TI  - Nucleus of tractus solitarius astrocytes as homeostatic integrators.

PMID- 22357840
TI  - Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and
      literature review.
AB  - PURPOSE: Mutations in PIK3CA [the gene encoding the p110alpha catalytic subunit
      of phosphatidylinositide-3-kinase (PI3K)] play an important role in colorectal
      carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20
      mutations trigger different biologic effects, and that concomitant mutations in
      both exons 9 and 20 synergistically enhance tumorigenic effects. Thus, we
      hypothesized that PIK3CA exon 9 and exon 20 mutations might have differential
      effects on clinical outcome in colorectal cancer, and that concomitant PIK3CA
      exon 9 and 20 mutations might confer aggressive tumor behavior. EXPERIMENTAL
      DESIGN: We sequenced PIK3CA by pyrosequencing in 1,170 rectal and colon cancers
      in two prospective cohort studies, and found 189 (16%) PIK3CA mutated tumors.
      Mortality HR according to PIK3CA status was computed using Cox proportional
      hazards model, adjusting for clinical and molecular features, including
      microsatellite instability, CpG island methylator phenotype, LINE-1 methylation,
      and BRAF and KRAS mutations. RESULTS: Compared with PIK3CA wild-type cases,
      patients with concomitant PIK3CA mutations in exons 9 and 20 experienced
      significantly worse cancer-specific survival [log-rank P = 0.031; multivariate HR
      = 3.51; 95% confidence interval (CI): 1.28-9.62] and overall survival (log-rank P
      = 0.0008; multivariate HR = 2.68; 95% CI: 1.24-5.77). PIK3CA mutation in either
      exon 9 or 20 alone was not significantly associated with patient survival. No
      significant interaction of PIK3CA mutation with BRAF or KRAS mutation was
      observed in survival analysis. CONCLUSION: Coexistence of PIK3CA (the PI3K
      p110alpha subunit) exon 9 and 20 mutations, but not PIK3CA mutation in either
      exon 9 or 20 alone, is associated with poor prognosis of colorectal cancer
      patients.

PMID- 22357842
TI  - Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a
      role in immediate early mGluR-stimulated translation.
AB  - Fragile X syndrome is caused by the loss of fragile X mental retardation protein
      (FMRP), which represses and reversibly regulates the translation of a subset of
      mRNAs in dendrites. Protein synthesis can be rapidly stimulated by mGluR-induced
      and protein phosphatase 2a (PP2A)-mediated dephosphorylation of FMRP, which is
      coupled to the dissociation of FMRP and target mRNAs from miRNA-induced silencing
      complexes. Here, we report the rapid ubiquitination and ubiquitin proteasome
      system (UPS)-mediated degradation of FMRP in dendrites upon DHPG (3,5
      dihydroxyphenylglycine) stimulation in cultured rat neurons. Using inhibitors to
      PP2A and FMRP phosphomutants, degradation of FMRP was observed to depend on its
      prior dephosphorylation. Translational induction of an FMRP target, postsynaptic
      density-95 mRNA, required both PP2A and UPS. Thus, control of FMRP levels at the
      synapse by dephosphorylation-induced and UPS-mediated degradation provides a mode
      to regulate protein synthesis.

PMID- 22357843
TI  - Interleukin-1 receptor accessory protein organizes neuronal synaptogenesis as a
      cell adhesion molecule.
AB  - Interleukin-1 receptor accessory protein (IL-1RAcP) is the essential component of
      receptor complexes mediating immune responses to interleukin-1 family cytokines.
      IL-1RAcP in the brain exists in two isoforms, IL-1RAcP and IL-1RAcPb, differing
      only in the C-terminal region. Here, we found robust synaptogenic activities of
      IL-1RAcP in cultured cortical neurons. Knockdown of IL-1RAcP isoforms in cultured
      cortical neurons suppressed synapse formation as indicated by decreases of active
      zone protein Bassoon puncta and dendritic protrusions. IL-1RAcP recovered the
      accumulation of presynaptic Bassoon puncta, while IL-1RAcPb rescued both Bassoon
      puncta and dendritic protrusions. Consistently, the expression of IL-1RAcP in
      cortical neurons enhances the accumulation of Bassoon puncta and that of IL
      1RAcPb stimulated both Bassoon puncta accumulation and spinogenesis. IL-1RAcP
      interacted with protein tyrosine phosphatase (PTP) delta through the
      extracellular domain. Mini-exon peptides in the Ig-like domains of PTPdelta
      splice variants were critical for their efficient binding to IL-1RAcP. The
      synaptogenic activities of IL-1RAcP isoforms were diminished in cortical neurons
      from PTPdelta knock-out mice. Correspondingly, PTPdelta required IL-1RAcPb to
      induce postsynaptic differentiation. Thus, IL-1RAcPb bidirectionally regulated
      synapse formation of cortical neurons. Furthermore, the spine densities of
      cortical and hippocampal pyramidal neurons were reduced in IL-1RAcP knock-out
      mice lacking both isoforms. These results suggest that IL-1RAcP isoforms function
      as trans-synaptic cell adhesion molecules in the brain and organize synapse
      formation. Thus, IL-1RAcP represents an interesting molecular link between immune
      systems and synapse formation in the brain.

PMID- 22357844
TI  - Linking pain and the body: neural correlates of visually induced analgesia.
AB  - The visual context of seeing the body can reduce the experience of acute pain,
      producing a multisensory analgesia. Here we investigated the neural correlates of
      this "visually induced analgesia" using fMRI. We induced acute pain with an
      infrared laser while human participants looked either at their stimulated right
      hand or at another object. Behavioral results confirmed the expected analgesic
      effect of seeing the body, while fMRI results revealed an associated reduction of
      laser-induced activity in ipsilateral primary somatosensory cortex (SI) and
      contralateral operculoinsular cortex during the visual context of seeing the
      body. We further identified two known cortical networks activated by sensory
      stimulation: (1) a set of brain areas consistently activated by painful stimuli
      (the so-called "pain matrix"), and (2) an extensive set of posterior brain areas
      activated by the visual perception of the body ("visual body network").
      Connectivity analyses via psychophysiological interactions revealed that the
      visual context of seeing the body increased effective connectivity (i.e.,
      functional coupling) between posterior parietal nodes of the visual body network
      and the purported pain matrix. Increased connectivity with these posterior
      parietal nodes was seen for several pain-related regions, including somatosensory
      area SII, anterior and posterior insula, and anterior cingulate cortex. These
      findings suggest that visually induced analgesia does not involve an overall
      reduction of the cortical response elicited by laser stimulation, but is
      consequent to the interplay between the brain's pain network and a posterior
      network for body perception, resulting in modulation of the experience of pain.

PMID- 22357845
TI  - The representation of biological classes in the human brain.
AB  - Evidence of category specificity from neuroimaging in the human visual system is
      generally limited to a few relatively coarse categorical distinctions-e.g., faces
      versus bodies, or animals versus artifacts-leaving unknown the neural
      underpinnings of fine-grained category structure within these large domains. Here
      we use fMRI to explore brain activity for a set of categories within the animate
      domain, including six animal species-two each from three very different
      biological classes: primates, birds, and insects. Patterns of activity throughout
      ventral object vision cortex reflected the biological classes of the stimuli.
      Specifically, the abstract representational space-measured as dissimilarity
      matrices defined between species-specific multivariate patterns of brain activity
      correlated strongly with behavioral judgments of biological similarity of the
      same stimuli. This biological class structure was uncorrelated with structure
      measured in retinotopic visual cortex, which correlated instead with a
      dissimilarity matrix defined by a model of V1 cortex for the same stimuli.
      Additionally, analysis of the shape of the similarity space in ventral regions
      provides evidence for a continuum in the abstract representational space-with
      primates at one end and insects at the other. Further investigation into the
      cortical topography of activity that contributes to this category structure
      reveals the partial engagement of brain systems active normally for inanimate
      objects in addition to animate regions.

PMID- 22357846
TI  - Neurochemical enhancement of conscious error awareness.
AB  - How the brain monitors ongoing behavior for performance errors is a central
      question of cognitive neuroscience. Diminished awareness of performance errors
      limits the extent to which humans engage in corrective behavior and has been
      linked to loss of insight in a number of psychiatric syndromes (e.g., attention
      deficit hyperactivity disorder, drug addiction). These conditions share
      alterations in monoamine signaling that may influence the neural mechanisms
      underlying error processing, but our understanding of the neurochemical drivers
      of these processes is limited. We conducted a randomized, double-blind, placebo
      controlled, cross-over design of the influence of methylphenidate, atomoxetine,
      and citalopram on error awareness in 27 healthy participants. The error awareness
      task, a go/no-go response inhibition paradigm, was administered to assess the
      influence of monoaminergic agents on performance errors during fMRI data
      acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram,
      significantly improved the ability of healthy volunteers to consciously detect
      performance errors. Furthermore, this behavioral effect was associated with a
      strengthening of activation differences in the dorsal anterior cingulate cortex
      and inferior parietal lobe during the methylphenidate condition for errors made
      with versus without awareness. Our results have implications for the
      understanding of the neurochemical underpinnings of performance monitoring and
      for the pharmacological treatment of a range of disparate clinical conditions
      that are marked by poor awareness of errors.

PMID- 22357847
TI  - RAE-1, a novel PHR binding protein, is required for axon termination and synapse
      formation in Caenorhabditis elegans.
AB  - Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of
      Presynaptic Morphology-1) regulates axon termination and synapse formation. To
      understand the mechanism of how rpm-1 functions, we have used mass spectrometry
      to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein
      1) as an evolutionarily conserved binding partner. We define a RAE-1 binding
      region in RPM-1, and show that this binding interaction is conserved and also
      occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein
      associated with Myc). rae-1 loss of function causes similar axon and synapse
      defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4
      and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and
      that rae-1 functions downstream of rpm-1. These studies establish a novel
      postmitotic function for rae-1 in neuronal development.

PMID- 22357848
TI  - Rescue of dopamine transporter function in hypoinsulinemic rats by a D2 receptor
      ERK-dependent mechanism.
AB  - The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key
      regulator of extracellular DA. A rapidly growing literature implicates insulin as
      an important regulator of DAT function. We showed previously that amphetamine
      (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with
      the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic
      resonance imaging experiments revealed that the blood oxygenation level-dependent
      signal following acute AMPH administration in STZ-treated rats is reduced. Here,
      we report that these deficits are restored by repeated, systemic administration
      of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D(2) receptors
      indirectly by increasing extracellular DA. Supporting a role for D(2) receptors
      in mediating this "rescue," the effect was completely blocked by pre-treatment of
      STZ-treated rats with the D(2) receptor antagonist raclopride before systemic
      AMPH. D(2) receptors regulate DAT cell surface expression through ERK1/2
      signaling. In ex vivo striatal preparations, repeated AMPH injections increased
      immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not
      control rats. These data suggest that repeated exposure to AMPH can rescue, by
      activating D(2) receptors and p-ERK signaling, deficits in DAT function that
      result from hypoinsulinemia. Our data confirm the idea that disorders influencing
      insulin levels and/or signaling, such as diabetes and anorexia, can degrade DAT
      function and that insulin-independent pathways are present that may be exploited
      as potential therapeutic targets to restore normal DAT function.

PMID- 22357849
TI  - Neuronal projections from V1 to V2 in amblyopia.
AB  - The mechanism of amblyopia in children with congenital cataract is not understood
      fully, but studies in macaques have shown that geniculate synapses are lost in
      striate cortex (V1). To search for other projection abnormalities in amblyopia,
      the pathway from V1 to V2 was examined using a triple-label technique in three
      animals raised with monocular suture. [(3)H]proline was injected into one eye to
      label the ocular dominance columns. Cholera toxin B subunit conjugated to gold
      (CTB-Au) was injected into V2 to label V1 projection neurons. Alternate sections
      were processed for cytochrome oxidase (CO) and CTB-Au, or dipped for
      autoradiography. Eight fields of CTB-Au-labeled cells in V1 opposite injection
      sites were plotted in layers 2/3 or 4B. After thin stripe injection, labeled
      cells were concentrated in CO patches. Despite column shrinkage, cells in
      deprived and normal columns were equal in size and density in both layers 2/3 and
      4B. After pale or thick stripe injection, labeled cells were concentrated in
      interpatches. Only 23% of projection neurons originated from deprived columns.
      This reduction exceeded the degree of column shrinkage, a result explained by the
      fact that column shrinkage causes disproportionate loss of interpatch territory.
      These data indicate that early monocular form deprivation does not alter the
      segregation of patch and interpatch pathways to V2 stripes or cause selective
      loss or atrophy of V1 projection neurons. The effect of shrinkage of
      geniculocortical afferents in layer 4C following visual deprivation is not
      amplified further by attenuation of the amblyopic eye's projections from V1 to
      V2.

PMID- 22357850
TI  - MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation.
AB  - Milk-fat globule EGF factor-8 (MFG-E8, SED1, lactadherin) is known to mediate the
      phagocytic removal of apoptotic cells by bridging phosphatidylserine (PS)
      exposing cells and the vitronectin receptor (VR) on phagocytes. However, we show
      here that MFG-E8 can mediate phagocytosis of viable neurons during
      neuroinflammation induced by lipopolysaccharide (LPS), thereby causing neuronal
      death. In vitro, inflammatory neuronal loss is independent of apoptotic pathways,
      and is inhibited by blocking the PS/MFG-E8/VR pathway (by adding PS blocking
      antibodies, annexin V, mutant MFG-E8 unable to bind VR, or VR antagonist).
      Neuronal loss is absent in Mfge8 knock-out cultures, but restored by adding
      recombinant MFG-E8, without affecting inflammation. In vivo, LPS-induced neuronal
      loss is reduced in the striatum of Mfge8 knock-out mice or by coinjection of an
      MFG-E8 receptor (VR) inhibitor into the rat striatum. Our data show that blocking
      MFG-E8-dependent phagocytosis preserves live neurons, implying that phagocytosis
      actively contributes to neuronal death during brain inflammation.

PMID- 22357851
TI  - Phosphorylation of HSP27 by protein kinase D is essential for mediating
      neuroprotection against ischemic neuronal injury.
AB  - Heat shock protein 27 (HSP27) (or HSPB1) exerts cytoprotection against many
      cellular insults, including cerebral ischemia. We previously identified apoptosis
      signal-regulating kinase 1 (ASK1) as a critical downstream target of HSP27
      conferring the neuroprotective effects of HSP27 against neuronal ischemia.
      However, the function of HSP27 is highly influenced by posttranslational
      modification, with differential cellular effects based on phosphorylation at
      specific serine residues. The role of phosphorylation in neuronal ischemic
      neuroprotection is currently unknown. We have created transgenic mice and viral
      vectors containing HSP27 mutated at three critical serine residues (Ser15, Ser78,
      and Ser82) to either alanine (HSP27-A, nonphosphorylatable) or aspartate (HSP27
      D, phosphomimetic) residues. Under both in vitro and in vivo neuronal ischemic
      settings, overexpression of wild-type HSP27 (HSP27) and HSP27-D, but not HSP27-A,
      was neuroprotective and inhibited downstream ASK1 signaling pathways.
      Consistently, overexpressed HSP27 was phosphorylated by endogenous mechanisms
      when neurons were under ischemic stress, and single-point mutations identified
      Ser15 and Ser82 as critical for neuroprotection. Using a panel of inhibitors and
      gene knockdown approaches, we identified the upstream kinase protein kinase D
      (PKD) as the primary kinase targeting HSP27 directly for phosphorylation. PKD and
      HSP27 coimmunoprecipitated, and inhibition or knockdown of PKD abrogated the
      neuroprotective effects of HSP27 as well as the interaction with and inhibition
      of ASK1 signaling. Together, these data demonstrate that HSP27 requires PKD
      mediated phosphorylation for its suppression of ASK1 cell death signaling and
      neuroprotection against ischemic injury.

PMID- 22357853
TI  - Neutralization of soluble, synaptotoxic amyloid beta species by antibodies is
      epitope specific.
AB  - Several anti-amyloid beta (Abeta) antibodies are under evaluation for the
      treatment of Alzheimer's disease (AD). Clinical studies using the N-terminal
      directed anti-Abeta antibody bapineuzumab have demonstrated reduced brain PET
      Pittsburg-B signals, suggesting the reduction of Abeta plaques, and reduced
      levels of total and phosphorylated tau protein in the CSF of treated AD patients.
      Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated
      resolution of Abeta plaque and vascular burdens, neuritic dystrophy, and
      preservation of synaptic density in the transgenic APP mouse models. In contrast,
      few studies have evaluated the direct interaction of this antibody with
      synaptotoxic soluble Abeta species. In the current report, we demonstrated that
      3D6 binds to soluble, synaptotoxic assemblies of Abeta(1-42) and prevents
      multiple downstream functional consequences in rat hippocampal neurons including
      changes in glutamate AMPA receptor trafficking, AD-type tau phosphorylation, and
      loss of dendritic spines. In vivo, we further demonstrated that 3D6 prevents
      synaptic loss and acutely reverses the behavioral deficit in the contextual fear
      conditioning task in transgenic mouse models of AD, two endpoints thought to be
      linked to synaptotoxic soluble Abeta moieties. Importantly C-terminal anti-Abeta
      antibodies were ineffective on these endpoints. These results, taken with prior
      studies, suggest that N-terminal anti-Abeta antibodies effectively interact with
      both soluble and insoluble forms of Abeta and therefore appear particularly well
      suited for testing the Abeta hypothesis of AD.

PMID- 22357852
TI  - Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect
      of endogenous adenosine.
AB  - Endogenous adenosine is an essential protective agent against neural damage by
      various insults to the brain. However, the therapeutic potential of adenosine
      receptor-directed ligands for neuroprotection is offset by side effects in
      peripheral tissues and organs. An increase in adenosine receptor responsiveness
      to endogenous adenosine would enhance neuroprotection while avoiding the
      confounding effects of exogenous ligands. Here we report novel regulation of
      adenosine-evoked responses by a neural tissue-specific protein, neurabin.
      Neurabin attenuated adenosine A(1) receptor (A1R) signaling by assembling a
      complex between the A1R and the regulator of G-protein signaling 4 (RGS4), a
      protein known to turn off G-protein signaling. Inactivation of the neurabin gene
      enhanced A1R signaling and promoted the protective effect of adenosine against
      excitotoxic seizure and neuronal death in mice. Furthermore, administration of a
      small molecule inhibitor of RGS4 significantly attenuated seizure severity in
      mice. Notably, the dose of kainate capable of inducing an ~50% rate of death in
      wild-type (WT) mice did not affect neurabin-null mice or WT mice cotreated with
      an RGS4 inhibitor. The enhanced anti-seizure and neuroprotective effect achieved
      by disruption of the A1R/neurabin/RGS4 complex is elicited by the on-site and on
      demand release of endogenous adenosine, and does not require administration of
      A1R ligands. These data identify neurabin-RGS4 as a novel tissue-selective
      regulatory mechanism for fine-tuning adenosine receptor function in the nervous
      system. Moreover, these findings implicate the A1R/neurabin/RGS4 complex as a
      valid therapeutic target for specifically manipulating the neuroprotective
      effects of endogenous adenosine.

PMID- 22357854
TI  - Emergence of stable functional networks in long-term human
      electroencephalography.
AB  - Functional connectivity networks have become a central focus in neuroscience
      because they reveal key higher-dimensional features of normal and abnormal
      nervous system physiology. Functional networks reflect activity-based coupling
      between brain regions that may be constrained by relatively static anatomical
      connections, yet these networks appear to support tremendously dynamic behaviors.
      Within this growing field, the stability and temporal characteristics of
      functional connectivity brain networks have not been well characterized. We
      evaluated the temporal stability of spontaneous functional connectivity networks
      derived from multi-day scalp encephalogram (EEG) recordings in five healthy human
      subjects. Topological stability and graph characteristics of networks derived
      from averaged data epochs ranging from 1 s to multiple hours across different
      states of consciousness were compared. We show that, although functional networks
      are highly variable on the order of seconds, stable network templates emerge
      after as little as ~100 s of recording and persist across different states and
      frequency bands (albeit with slightly different characteristics in different
      states and frequencies). Within these network templates, the most common edges
      are markedly consistent, constituting a network "core." Although average network
      topologies persist across time, measures of global network connectivity, density
      and clustering coefficient, are state and frequency specific, with sparsest but
      most highly clustered networks seen during sleep and in the gamma frequency band.
      These findings support the notion that a core functional organization underlies
      spontaneous cortical processing and may provide a reference template on which
      unstable, transient, and rapidly adaptive long-range assemblies are overlaid in a
      frequency-dependent manner.

PMID- 22357855
TI  - Sodium-activated potassium channels are functionally coupled to persistent sodium
      currents.
AB  - We report a novel coupled system of sodium-activated potassium currents (I(KNa))
      and persistent sodium currents (I(NaP)), the components of which are widely
      distributed throughout the brain. Its existence and importance has not been
      previously recognized. Although I(KNa) was known to exist in many cell types, the
      source of Na(+) which activates I(KNa) remained a mystery. We now show in single
      membrane patches generated from the somas of rat neurons that sodium influx
      through I(NaP) is sufficient for activation of K(Na) channels, without
      substantial contribution from the transient sodium current or bulk [Na(+)](i).
      I(NaP) was found to be active at cell membrane resting potentials, a finding that
      may explain why I(KNa) can be evoked from negative holding potentials. These
      results show an unanticipated role for I(NaP) in activating a negative feedback
      system countering the excitable effects I(NaP); the interrelatedness of I(NaP)
      and I(KNa) suggests new ways neurons can tune their excitability.

PMID- 22357856
TI  - Phospholipase C-mediated suppression of dark noise enables single-photon
      detection in Drosophila photoreceptors.
AB  - Drosophila photoreceptor cells use the ubiquitous G-protein-mediated
      phospholipase C (PLC) cascade to achieve ultimate single-photon sensitivity. This
      is manifested in the single-photon responses (quantum bumps). In photoreceptor
      cells, dark activation of G(q)alpha molecules occurs spontaneously and produces
      unitary dark events (dark bumps). A high rate of spontaneous G(q)alpha activation
      and dark bump production potentially hampers single-photon detection. We found
      that in wild-type flies the in vivo rate of spontaneous G(q)alpha activation is
      very high. Nevertheless, this high rate is not manifested in a substantially high
      rate of dark bumps. Therefore, it is unclear how phototransduction suppresses
      dark bump production arising from spontaneous G(q)alpha activation, while still
      maintaining high-fidelity representation of single photons. In this study we show
      that reduced PLC catalytic activity selectively suppressed production of dark
      bumps but not light-induced bumps. Manipulations of PLC activity using PLC mutant
      flies and Ca(2+) modulations revealed that a critical level of PLC activity is
      required to induce bump production. The required minimal level of PLC activity
      selectively suppressed random production of single G(q)alpha-activated dark bumps
      despite a high rate of spontaneous G(q)alpha activation. This minimal PLC
      activity level is reliably obtained by photon-induced synchronized activation of
      several neighboring G(q)alpha molecules activating several PLC molecules, but not
      by random activation of single G(q)alpha molecules. We thus demonstrate how a G
      protein-mediated transduction system, with PLC as its target, selectively
      suppresses its intrinsic noise while preserving reliable signaling.

PMID- 22357857
TI  - Transient extracellular glutamate events in the basolateral amygdala track reward
      seeking actions.
AB  - The ability to make rapid, informed decisions about whether or not to engage in a
      sequence of actions to earn reward is essential for survival. Modeling in rodents
      has demonstrated a critical role for the basolateral amygdala (BLA) in such
      reward-seeking actions, but the precise neurochemical underpinnings are not well
      understood. Taking advantage of recent advancements in biosensor technologies, we
      made spatially discrete near-real-time extracellular recordings of the major
      excitatory transmitter, glutamate, in the BLA of rats performing a self-paced
      lever-pressing sequence task for sucrose reward. This allowed us to detect rapid
      transient fluctuations in extracellular BLA glutamate time-locked to action
      performance. These glutamate transients tended to precede lever-pressing actions
      and were markedly increased in frequency when rats were engaged in such reward
      seeking actions. Based on muscimol and tetrodotoxin microinfusions, these
      glutamate transients appeared to originate from the terminals of neurons with
      cell bodies in the orbital frontal cortex. Importantly, glutamate transient
      amplitude and frequency fluctuated with the value of the earned reward and
      positively predicted lever-pressing rate. Such novel rapid glutamate recordings
      during instrumental performance identify a role for glutamatergic signaling
      within the BLA in instrumental reward-seeking actions.

PMID- 22357858
TI  - Memory-guided sensory comparisons in the prefrontal cortex: contribution of
      putative pyramidal cells and interneurons.
AB  - Comparing two stimuli that occur at different times demands the coordination of
      bottom-up and top-down processes. It has been hypothesized that the dorsolateral
      prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays
      a key role in such tasks, contributing to both maintenance and sensory
      comparisons. We examined this hypothesis by recording from the PFC of monkeys
      comparing directions of two moving stimuli, S1 and S2, separated by a memory
      delay. We determined the contribution of the two principal cell types to these
      processes by classifying neurons into broad-spiking (BS) putative pyramidal cells
      and narrow-spiking (NS) putative local interneurons. During the delay, BS cells
      were more likely to exhibit anticipatory modulation and represent the remembered
      direction. While this representation was transient, appearing at different times
      in different neurons, it weakened when direction was not task relevant,
      suggesting its utility. During S2, both putative cell types showed comparison
      related activity modulations. These modulations were of two types, each carried
      by different neurons, which either preferred trials with stimuli moving in the
      same direction or trials with stimuli of different directions. These comparison
      effects were strongly correlated with choice, suggesting their role in circuitry
      underlying decision making. These results provide the first demonstration of
      distinct contributions made by principal cell types to memory-guided perceptual
      decisions. During sensory stimulation both cell types represent behaviorally
      relevant stimulus features contributing to comparison and decision-related
      activity. However in the absence of sensory stimulation, putative pyramidal cells
      dominated, carrying information about the elapsed time and the preceding
      direction.

PMID- 22357859
TI  - Hair bundle defects and loss of function in the vestibular end organs of mice
      lacking the receptor-like inositol lipid phosphatase PTPRQ.
AB  - Recent studies have shown that mutations in PTPRQ, a gene encoding a receptor
      like inositol lipid phosphatase, cause recessive, nonsyndromic, hereditary
      hearing loss with associated vestibular dysfunction. Although null mutations in
      Ptprq cause the loss of high-frequency auditory hair cells and deafness in mice,
      a loss of vestibular hair cells and overt behavioral defects characteristic of
      vestibular dysfunction have not been described. Hair bundle structure and
      vestibular function were therefore examined in Ptprq mutant mice. Between
      postnatal days 5 and 16, hair bundles in the extrastriolar regions of the utricle
      in Ptprq(-/-) mice become significantly longer than those in heterozygous
      controls. This increase in length (up to 50%) is accompanied by the loss and
      fusion of stereocilia. Loss and fusion of stereocilia also occurs in the striolar
      region of the utricle in Ptprq(-/-) mice, but is not accompanied by hair bundle
      elongation. These abnormalities persist until 12 months of age but are not
      accompanied by significant hair cell loss. Hair bundle defects are also observed
      in the saccule and ampullae of Ptprq(-/-) mice. At ~3 months of age, vestibular
      evoked potentials were absent from the majority (12 of 15) of Ptprq(-/-) mice
      examined, and could only be detected at high stimulus levels in the other 3
      mutants. Subtle but distinct defects in swimming behavior were detected in most
      (seven of eight) mutants tested. The results reveal a distinct phenotype in the
      vestibular system of Ptprq(-/-) mice and suggest similar hair bundle defects may
      underlie the vestibular dysfunction reported in humans with mutations in PTPRQ.

PMID- 22357860
TI  - Visuotopic cortical connectivity underlying attention revealed with white-matter
      tractography.
AB  - Visual attention selects behaviorally relevant information for detailed
      processing by resolving competition for representation among stimuli in
      retinotopically organized visual cortex. The signals that control this
      attentional biasing are thought to arise in a frontoparietal network of several
      brain regions, including posterior parietal cortex. Recent studies have revealed
      a topographic organization in the intraparietal sulcus (IPS) that mirrors the
      retinotopic organization in visual cortex, suggesting that connectivity between
      these regions might provide the mechanism by which attention acts on early
      cortical representations. Using white-matter imaging and functional MRI, we
      examined the connectivity between two topographic regions of IPS and six
      retinotopically defined areas in visual cortex. We observed a strong positive
      correlation between attention modulations in visual cortex and connectivity of
      posterior IPS, suggesting that these white-matter connections mediate the
      attention signals that resolve competition among stimuli for representation in
      visual cortex. Furthermore, we found that connectivity between IPS and V1
      consistently respects visuotopic boundaries, whereas connections to V2 and V3/VP
      disperse by 60%. This pattern is consistent with changes in receptive field size
      across regions and suggests that a primary role of posterior IPS is to code
      spatially specific visual information. In summary, we have identified white
      matter pathways that are ideally suited to carry attentional biasing signals in
      visuotopic coordinates from parietal control regions to sensory regions in
      humans. These results provide critical evidence for the biased competition theory
      of attention and specify neurobiological constraints on the functional brain
      organization of visual attention.

PMID- 22357862
TI  - Suppression of a MEF2-KLF6 survival pathway by PKA signaling promotes apoptosis
      in embryonic hippocampal neurons.
AB  - In the mammalian nervous system, regulation of transcription factor activity is a
      crucial determinant of neuronal cell survival, differentiation, and death. The
      myocyte enhancer factor 2 (MEF2) transcription factors have been implicated in
      cellular processes underlying neuronal survival and differentiation. A core
      component of the MEF2 complex is the MEF2D subunit. Recently, we reported that
      cAMP-dependent protein kinase (cAMP/PKA) signaling negatively regulates MEF2D
      function in myogenic cells. Here, we assessed whether cAMP signaling converges on
      the prosurvival role of MEF2D in Sprague Dawley rat embryonic (E18) hippocampal
      neurons. Initially, we observed that experimental induction of cAMP/PKA signaling
      promotes apoptosis in primary hippocampal neurons as indicated by TUNEL and FACS
      analysis. Luciferase reporter gene assays revealed that PKA potently represses
      MEF2D trans-activation properties in neurons. This effect was largely reversed by
      engineered neutralizing mutations of PKA phospho-acceptor sites on MEF2D
      (S121/190A). Kruppel-like factor 6 (KLF6) was identified as a key transcriptional
      target of MEF2 in hippocampal neurons, and siRNA-mediated knockdown of KLF6
      expression promotes neuronal cell death and also antagonizes the prosurvival role
      of MEF2D. These observations have important implications for understanding the
      pathways controlling cell survival and death in the mammalian nervous system.

PMID- 22357861
TI  - Dynamics of normalization underlying masking in human visual cortex.
AB  - Stimulus visibility can be reduced by other stimuli that overlap the same region
      of visual space, a process known as masking. Here we studied the neural
      mechanisms of masking in humans using source-imaged steady state visual evoked
      potentials and frequency-domain analysis over a wide range of relative stimulus
      strengths of test and mask stimuli. Test and mask stimuli were tagged with
      distinct temporal frequencies and we quantified spectral response components
      associated with the individual stimuli (self terms) and responses due to
      interaction between stimuli (intermodulation terms). In early visual cortex,
      masking alters the self terms in a manner consistent with a reduction of input
      contrast. We also identify a novel signature of masking: a robust intermodulation
      term that peaks when the test and mask stimuli have equal contrast and disappears
      when they are widely different. We fit all of our data simultaneously with family
      of a divisive gain control models that differed only in their dynamics. Models
      with either very short or very long temporal integration constants for the gain
      pool performed worse than a model with an integration time of ~30 ms. Finally,
      the absolute magnitudes of the response were controlled by the ratio of the
      stimulus contrasts, not their absolute values. This contrast-contrast invariance
      suggests that many neurons in early visual cortex code relative rather than
      absolute contrast. Together, these results provide a more complete description of
      masking within the normalization framework of contrast gain control and suggest
      that contrast normalization accomplishes multiple functional goals.

PMID- 22357863
TI  - Improved sequence learning with subthalamic nucleus deep brain stimulation:
      evidence for treatment-specific network modulation.
AB  - We used a network approach to study the effects of anti-parkinsonian treatment on
      motor sequence learning in humans. Eight Parkinson's disease (PD) patients with
      bilateral subthalamic nucleus (STN) deep brain stimulation underwent H(2)(15)O
      positron emission tomography (PET) imaging to measure regional cerebral blood
      flow (rCBF) while they performed kinematically matched sequence learning and
      movement tasks at baseline and during stimulation. Network analysis revealed a
      significant learning-related spatial covariance pattern characterized by
      consistent increases in subject expression during stimulation (p = 0.008,
      permutation test). The network was associated with increased activity in the
      lateral cerebellum, dorsal premotor cortex, and parahippocampal gyrus, with
      covarying reductions in the supplementary motor area (SMA) and orbitofrontal
      cortex. Stimulation-mediated increases in network activity correlated with
      concurrent improvement in learning performance (p < 0.02). To determine whether
      similar changes occurred during dopaminergic pharmacotherapy, we studied the
      subjects during an intravenous levodopa infusion titrated to achieve a motor
      response equivalent to stimulation. Despite consistent improvement in motor
      ratings during infusion, levodopa did not alter learning performance or network
      activity. Analysis of learning-related rCBF in network regions revealed
      improvement in baseline abnormalities with STN stimulation but not levodopa.
      These effects were most pronounced in the SMA. In this region, a consistent rCBF
      response to stimulation was observed across subjects and trials (p = 0.01),
      although the levodopa response was not significant. These findings link the
      cognitive treatment response in PD to changes in the activity of a specific
      cerebello-premotor cortical network. Selective modulation of overactive SMA-STN
      projection pathways may underlie the improvement in learning found with
      stimulation.

PMID- 22357864
TI  - An essential role for modulation of hyperpolarization-activated current in the
      development of binaural temporal precision.
AB  - In sensory circuits of the brain, developmental changes in the expression and
      modulation of voltage-gated ion channels are a common occurrence, but such
      changes are often difficult to assign to clear functional roles. We have explored
      this issue in the binaural neurons of the medial superior olive (MSO), whose
      temporal precision in detecting the coincidence of binaural inputs dictates the
      resolution of azimuthal sound localization. We show that in MSO principal neurons
      of gerbils during the first week of hearing, a hyperpolarization-activated
      current (I(h)) progressively undergoes a 13-fold increase in maximal conductance,
      a >10-fold acceleration of kinetics, and, most surprisingly, a 30 mV depolarizing
      shift in the voltage dependence of activation. This period is associated with an
      upregulation of the hyperpolarization-activated and cyclic nucleotide-gated (HCN)
      channel subunits HCN1, HCN2, and HCN4 in the MSO, but only HCN1 and HCN4 were
      expressed strongly in principal neurons. I(h) recorded in nucleated patches from
      electrophysiologically mature MSO neurons (>P18) exhibited kinetics and an
      activation range nearly identical to the I(h) found in whole-cell recordings
      before hearing onset. These results indicate that the developmental changes in
      I(h) in MSO neurons can be explained predominantly by modulation from diffusible
      intracellular factors, and not changes in channel subunit composition. The
      exceptionally large modulatory changes in I(h), together with refinements in
      synaptic properties transform the coding strategy from one of summation and
      integration to the submillisecond coincidence detection known to be required for
      transmission of sound localization cues.

PMID- 22357866
TI  - Frontal eye field neurons assess visual stability across saccades.
AB  - The image on the retina may move because the eyes move, or because something in
      the visual scene moves. The brain is not fooled by this ambiguity. Even as we
      make saccades, we are able to detect whether visual objects remain stable or
      move. Here we test whether this ability to assess visual stability across
      saccades is present at the single-neuron level in the frontal eye field (FEF), an
      area that receives both visual input and information about imminent saccades. Our
      hypothesis was that neurons in the FEF report whether a visual stimulus remains
      stable or moves as a saccade is made. Monkeys made saccades in the presence of a
      visual stimulus outside of the receptive field. In some trials, the stimulus
      remained stable, but in other trials, it moved during the saccade. In every
      trial, the stimulus occupied the center of the receptive field after the saccade,
      thus evoking a reafferent visual response. We found that many FEF neurons
      signaled, in the strength and timing of their reafferent response, whether the
      stimulus had remained stable or moved. Reafferent responses were tuned for the
      amount of stimulus translation, and, in accordance with human psychophysics,
      tuning was better (more prevalent, stronger, and quicker) for stimuli that moved
      perpendicular, rather than parallel, to the saccade. Tuning was sometimes present
      as well for nonspatial transaccadic changes (in color, size, or both). Our
      results indicate that FEF neurons evaluate visual stability during saccades and
      may be general purpose detectors of transaccadic visual change.

PMID- 22357865
TI  - Integrin beta1 signals through Arg to regulate postnatal dendritic arborization,
      synapse density, and behavior.
AB  - Integrins are heterodimeric extracellular matrix receptors that are essential for
      the proper development of the vertebrate nervous system. We report here that
      selective loss of integrin beta1 in excitatory neurons leads to reductions in the
      size and complexity of hippocampal dendritic arbors, hippocampal synapse loss,
      impaired hippocampus-dependent learning, and exaggerated psychomotor sensitivity
      to cocaine in mice. Our biochemical and genetic experiments demonstrate that the
      intracellular tail of integrin beta1 binds directly to Arg kinase and that this
      interaction stimulates activity of the Arg substrate p190RhoGAP, an inactivator
      of the RhoA GTPase. Moreover, genetic manipulations that reduce integrin beta1
      signaling through Arg recapitulate the integrin beta1 knock-out phenotype in a
      gene dose-sensitive manner. Together, these results describe a novel integrin
      beta1-Arg-p190RhoGAP pathway that regulates dendritic arbor size, promotes
      synapse maintenance, supports proper hippocampal function, and mitigates the
      behavioral consequences of cocaine exposure.

PMID- 22357868
TI  - Reward action in the initiation of smooth pursuit eye movements.
AB  - Reward has a powerful influence on motor behavior. To probe how and where reward
      systems alter motor behavior, we studied smooth pursuit eye movements in monkeys
      trained to associate the color of a visual cue with the size of the reward to be
      issued at the end of the target motion. When the tracking task presented two
      different colored targets that moved orthogonally, monkeys biased the initiation
      of pursuit toward the direction of motion of the target that led to larger
      reward. The bias was larger than expected given the modest effects of reward size
      on tracking of single targets. Experiments with three different reward sizes
      suggested that the bias afforded a given target depends mainly on the size of the
      larger reward. To analyze the effect of reward on directional learning in
      pursuit, monkeys tracked a single moving target that changed direction 250 ms
      after the onset of motion. Expectation of a larger reward led to a larger learned
      eye movement during the acquisition of the learned response and during subsequent
      probes of what had been learned, implying that reward influenced the expression
      rather than the acquisition of learning. The specific effects of reward size on
      learning and two-target stimuli imply that the site of reward modulation is at a
      level where multiple target motions compete for control of eye movement,
      downstream from sensory processing and learning and upstream from final motor
      processing.

PMID- 22357867
TI  - Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of
      neurotoxicity by FoxG1.
AB  - The methyl-CpG binding protein 2 (MeCP2) is a widely expressed protein, the
      mutations of which cause Rett syndrome. The level of MeCP2 is highest in the
      brain where it is expressed selectively in mature neurons. Its functions in
      postmitotic neurons are not known. The MeCP2 gene is alternatively spliced to
      generate two proteins with different N termini, designated as MeCP2-e1 and MeCP2
      e2. The physiological significance of these two isoforms has not been elucidated,
      and it is generally assumed they are functionally equivalent. We report that in
      cultured cerebellar granule neurons induced to die by low potassium treatment and
      in Abeta-treated cortical neurons, Mecp2-e2 expression is upregulated whereas
      expression of the Mecp2-e1 isoform is downregulated. Knockdown of Mecp2-e2
      protects neurons from death, whereas knockdown of the e1 isoform has no effect.
      Forced expression of MeCP2-e2, but not MeCP2-e1, promotes apoptosis in otherwise
      healthy neurons. We find that MeCP2-e2 interacts with the forkhead protein FoxG1,
      mutations of which also cause Rett syndrome. FoxG1 has been shown to promote
      neuronal survival and its downregulation leads to neuronal death. We find that
      elevated FoxG1 expression inhibits MeCP2-e2 neurotoxicity. MeCP2-e2 neurotoxicity
      is also inhibited by IGF-1, which prevents the neuronal death-associated
      downregulation of FoxG1 expression, and by Akt, the activation of which is
      necessary for FoxG1-mediated neuroprotection. Finally, MeCP2-e2 neurotoxicity is
      enhanced if FoxG1 expression is suppressed or in neurons cultured from FoxG1
      haplodeficient mice. Our results indicate that Mecp2-e2 promotes neuronal death
      and that this activity is normally inhibited by FoxG1. Reduced FoxG1 expression
      frees MecP2-e2 to promote neuronal death.

PMID- 22357869
TI  - Effects of axonal topology on the somatic modulation of synaptic outputs.
AB  - Depolarization of the neuronal soma augments synaptic output onto postsynaptic
      neurons via long-range, axonal cable properties. Here, we report that the range
      of this somatic influence is spatially restricted by not only axonal path length
      but also a branching-dependent decrease in axon diameter. Cell-attached
      recordings of action potentials (APs) from multiple axon branches of a rat
      hippocampal CA3 pyramidal cell revealed that an AP was broadened following a 20
      mV depolarization of the soma and reverted to a normal width during propagation
      down the axon. The narrowing of the AP depended on the distance traveled by the
      AP and on the number of axon branch points through which the AP passed. These
      findings were confirmed by optical imaging of AP-induced calcium elevations in
      presynaptic boutons, suggesting that the somatic membrane potential modifies
      synaptic outputs near the soma but not long-projection outputs. Consistent with
      this prediction, whole-cell recordings from synaptically connected neurons
      revealed that depolarization of presynaptic CA3 pyramidal cells facilitated
      synaptic transmission to nearby CA3 pyramidal cells, but not to distant pyramidal
      cells in CA3 or CA1. Therefore, axonal geometry enables the differential
      modulation of synaptic output depending on target location.

PMID- 22357870
TI  - C-terminal complexin sequence is selectively required for clamping and priming
      but not for Ca2+ triggering of synaptic exocytosis.
AB  - Complexins are small soluble proteins that bind to assembling SNARE complexes
      during synaptic vesicle exocytosis, which in turn mediates neurotransmitter
      release. Complexins are required for clamping of spontaneous "mini " release and
      for the priming and synaptotagmin-dependent Ca(2+) triggering of evoked release.
      Mammalian genomes encode four complexins that are composed of an N-terminal
      unstructured sequence that activates synaptic exocytosis, an accessory alpha
      helix that clamps exocytosis, an essential central alpha-helix that binds to
      assembling SNARE complexes and is required for all of its functions, and a long,
      apparently unstructured C-terminal sequence whose function remains unclear. Here,
      we used cultured mouse neurons to show that the C-terminal sequence of complexin
      1 is not required for its synaptotagmin-activating function but is essential for
      its priming and clamping functions. Wild-type complexin-3 did not clamp
      exocytosis but nevertheless fully primed and activated exocytosis. Strikingly,
      exchanging the complexin-1 C terminus for the complexin-3 C terminus abrogated
      clamping, whereas exchanging the complexin-3 C terminus for the complexin-1 C
      terminus enabled clamping. Analysis of point mutations in the complexin-1 C
      terminus identified two single amino-acid substitutions that impaired clamping
      without altering the activation function of complexin-1. Examination of release
      induced by stimulus trains revealed that clamping-deficient C-terminal complexin
      mutants produced a modest relative increase in delayed release. Overall, our
      results show that the relatively large C-terminal complexin-1 sequence acts in
      priming and clamping synaptic exocytosis and demonstrate that the clamping
      function is not conserved in complexin-3, presumably because of its distinct C
      terminal sequences.

PMID- 22357871
TI  - Separate prefrontal-subcortical circuits mediate different components of risk
      based decision making.
AB  - Choosing between smaller, assured rewards or larger, uncertain ones requires
      reconciliation of competing biases toward more certain or riskier options. We
      used disconnection and neuroanatomical techniques to reveal that separate, yet
      interconnected, neural pathways linking the medial prefrontal cortex (PFC), the
      basolateral amygdala (BLA), and nucleus accumbens (NAc) contribute to these
      different decision biases in rats. Disrupting communication between the BLA and
      NAc revealed that this subcortical circuit biases choice toward larger, uncertain
      rewards on a probabilistic discounting task. In contrast, disconnections between
      the BLA and PFC increased choice of the Large/Risky option. PFC-NAc
      disconnections did not affect choice but did increase choice latencies and trial
      omissions. Neuroanatomical studies confirmed that projection pathways carrying
      axons from BLA-to-PFC transverse a distinctly different route relative to PFC-to
      BLA pathways (via the ventrolateral amydalofugal pathway and ventromedial
      internal capsule, respectively). We exploited these dissociable axonal pathways
      to selectively disrupt bottom-up and top-down communication between the BLA and
      PFC. Subsequent disconnection studies revealed that disruption of top-down (but
      not bottom-up) information transfer between the medial PFC and BLA increased
      choice of the larger, riskier option, suggesting that this circuit facilitates
      tracking of actions and outcomes to temper urges for riskier rewards as they
      become less profitable. These findings provide novel insight into the dynamic
      competition between these cortical/subcortical circuits that shape our decision
      biases and underlie conflicting urges when evaluating options that vary in terms
      of potential risks and rewards.

PMID- 22357872
TI  - Spontaneous olfactory receptor neuron activity determines follower cell response
      properties.
AB  - Noisy or spontaneous activity is common in neural systems and poses a challenge
      to detecting and discriminating signals. Here we use the locust to answer
      fundamental questions about noise in the olfactory system: Where does spontaneous
      activity originate? How is this activity propagated or reduced throughout
      multiple stages of neural processing? What mechanisms favor the detection of
      signals despite the presence of spontaneous activity? We found that spontaneous
      activity long observed in the secondary projection neurons (PNs) originates
      almost entirely from the primary olfactory receptor neurons (ORNs) rather than
      from spontaneous circuit interactions in the antennal lobe, and that spontaneous
      activity in ORNs tonically depolarizes the resting membrane potentials of their
      target PNs and local neurons (LNs) and indirectly tonically depolarizes tertiary
      Kenyon cells (KCs). However, because these neurons have different response
      thresholds, in the absence of odor stimulation, ORNs and PNs display a high
      spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation
      of the olfactory network to show that discrimination of signal and noise in the
      KCs is best when threshold levels are set so that baseline activity in PNs
      persists. Our results show how the olfactory system benefits from making a signal
      detection decision after a point of maximal information convergence, e.g., after
      KCs pool inputs from many PNs.

PMID- 22357873
TI  - Homogeneous screening assay for human tankyrase.
AB  - Tankyrase, a member of human PARP protein superfamily, catalyzes a covalent post
      translational modification of substrate proteins. This modification, poly(ADP
      ribos)ylation, leads to changes in protein interactions and modifies downstream
      signaling events. Tankyrase 1 is a potential drug target due to its functions in
      telomere homeostasis and in Wnt signaling. We describe here optimization and
      application of an activity-based homogenous assay for tankyrase inhibitors in a
      high-throughput screening format. The method measures the consumption of
      substrate by the chemical conversion of the remaining NAD(+) into a stable
      fluorescent condensation product. Conditions were optimized to measure the
      enzymatic auto-modification of a recombinant catalytic fragment of tankyrase 1.
      The fluorescence assay is inexpensive, operationally easy and performs well
      according to the statistical analysis (Z'= 0.7). A validatory screen with a
      natural product library confirmed suitability of the assay for finding new
      tankyrase inhibitors. Flavone was the most potent (IC(50)=325 nM) hit from the
      natural compounds. A flavone derivative, apigenin, and isopropyl gallate showed
      potency on the micromolar range, but displayed over 30-fold selectivity for
      tankyrase over the studied isoenzymes PARP1 and PARP2. The assay is robust and
      will be useful for screening new tankyrase inhibitors.

PMID- 22357874
TI  - Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high
      throughput screen to identify compounds that modulate VHL proteostasis.
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that affects
      multiple organs. Treatment is mainly surgical, and effective systemic therapies
      are needed. We developed a cell-based screening tool to identify compounds that
      stabilize or upregulate full-length, point-mutated VHL protein. The 786-0 cell
      line was infected with full-length W117A-mutated VHL linked to a C-terminal Venus
      fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick
      drug library and was tested against proteasome inhibitors MG132 and bortezomib.
      Western blot validation and evaluation of functional readouts, including hypoxia
      inducible factor 2alpha (HIF2alpha) and glucose transporter 1 (Glut1) levels,
      were performed. We found that bortezomib, MG132, and the Prestwick compounds 8
      azaguanine, thiostrepton, and thioguanosine upregulated VHL-W117A-Venus in 786-0
      cells. 8-Azaguanine downregulated HIF2alpha levels and was augmented by the
      presence of VHL W117A. VHL p30 band intensities varied as a function of compound
      used, suggesting alternate posttranslational processing. Nuclear-cytoplasmic
      localization of VHL-W117A-Venus varied among the different compounds. In
      conclusion, a 786-0 cell line containing VHL-W117A-Venus was successfully used to
      identify compounds that upregulate VHL levels, with differential effect on VHL
      intracellular localization and posttranslational processing. Further screening
      efforts will broaden the number of pharmacophores available to develop
      therapeutic agents that will upregulate and refunctionalize mutated VHL.

PMID- 22357875
TI  - The effect of increased fetal hemoglobin on 7 common Hb A1c assay methods.

PMID- 22357876
TI  - Should I repeat my 1:2s QC rejection?
AB  - BACKGROUND: Repeating a QC that is outside 2SD from the mean (1:2s rule) appears
      to be a common practice. Although this form of repeat sampling is frowned on by
      many, the comparative power of the approach has not been formally evaluated.
      METHODS: We computed power functions mathematically and by computer simulation
      for 4 different 1:2s repeat-sampling strategies, as well as the 1:2s rule, the
      1:3s rule, and 2 common QC multirules. RESULTS: The false-rejection rates for the
      repeat-sampling strategies were similarly low to those of the 1:3s QC rule. The
      error detection rates for the repeat-sampling strategies approached those of the
      1:2s QC rule for moderate to large out-of-control error conditions. In most
      cases, the power of the repeat-sampling strategies was superior to the power of
      the QC multirules we evaluated. The increase in QC utilization rate ranged from
      4% to 13% for the repeat-sampling strategies investigated. CONCLUSIONS: The
      repeat-sampling strategies provide an effective tactic to take advantage of the
      desirable properties of both the 1:2s and 1:3s QC rules. Additionally, the power
      of the repeat-sampling strategies compares favorably with the power of 2 common
      QC multirules. These improvements come with a modest increase in the average
      number of controls tested.

PMID- 22357877
TI  - Science to practice: what do molecular biologic studies in rodent models add to
      our understanding of interventional oncologic procedures including percutaneous
      ablation by using glyceraldehyde-3-phosphate dehydrogenase antagonists?
AB  - In this basic research study, Ganapathy-Kanniappan et al advance our
      understanding of how to block the glycolytic pathway to inhibit tumor progression
      by using image guided procedures (1). This was accomplished by demonstrating
      their ability to perform molecular targeting of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in human hepatocellular carcinoma (HCC) by using
      percutaneous injection of either inhibitor--3-bromopyruvate (3-BrPA) or short
      hairpin RNA (shRNA). They take the critical step of providing further rationale
      for potentially advancing this therapy into clinical trials by demonstrating that
      GAPDH expression strongly correlates with c-jun, a proto-oncogene involved in
      liver tumorigenesis in human HCC (2).

PMID- 22357878
TI  - Tissue characterization with cardiac MR imaging: a new hope for improving the
      cardiac outlook of patients with impaired fasting glucose?

PMID- 22357879
TI  - CT as an outcome surrogate in patients with cystic fibrosis: does the effort
      justify the risks?

PMID- 22357880
TI  - The revised Atlanta classification of acute pancreatitis: its importance for the
      radiologist and its effect on treatment.
AB  - An international working group has modified the Atlanta classification for acute
      pancreatitis to update the terminology and provide simple functional clinical and
      morphologic classifications. The modifications (a) address the clinical course
      and severity of disease, (b) divide acute pancreatitis into interstitial
      edematous pancreatitis and necrotizing pancreatitis, (c) distinguish an early
      phase (1st week) and a late phase (after the 1st week), and (d) emphasize
      systemic inflammatory response syndrome and multisystem organ failure. In the 1st
      week, only clinical parameters are important for treatment planning. After the
      1st week, morphologic criteria defined on the basis of computed tomographic
      findings are combined with clinical parameters to help determine care. This
      revised classification introduces new terminology for pancreatic fluid
      collections. Depending on presence or absence of necrosis, acute collections in
      the first 4 weeks are called acute necrotic collections or acute peripancreatic
      fluid collections. Once an enhancing capsule develops, persistent acute
      peripancreatic fluid collections are referred to as pseudocysts; and acute
      necrotic collections, as walled-off necroses. All can be sterile or infected.
      Terms such as pancreatic abscess and intrapancreatic pseudocyst have been
      abandoned. The goal is for radiologists, gastroenterologists, surgeons, and
      pathologists to use the revised classifications to standardize imaging
      terminology to facilitate treatment planning and enable precise comparison of
      results among different departments and institutions.

PMID- 22357881
TI  - Critical review and state of the art in interventional oncology: benign and
      metastatic disease involving bone.
AB  - Image-guided percutaneous ablation methods have proved effective for treatment of
      benign bone tumors and for palliation of metastases involving bone and soft
      tissue sites beyond the liver and lung. Image-guided radiofrequency ablation is
      now the standard treatment for osteoid osteoma, as the procedure can be performed
      with higher rates of technical success, decreased morbidity, and lower cost than
      those obtained with open surgery. Several ablation methods have been used to
      effectively palliate focal painful metastatic disease involving bone and soft
      tissue sites beyond the liver and lung. Substantial pain reduction is possible in
      patients who have failed to achieve benefit from conventional therapies,
      including chemotherapy and external-beam radiation. Importantly, the pain
      reduction that is achieved is durable over many months of observation.

PMID- 22357882
TI  - The Bosniak renal cyst classification: 25 years later.
AB  - In the past 25 years, there have been continuous advances in the diagnosis of
      disease throughout the body owing to the introduction of new technology and the
      experience gained with its use. However, the imaging and evaluation of
      complicated cystic lesions of the kidneys frequently remains a difficult problem.
      The classification of renal cystic lesions suggested 25 years ago, now referred
      to as the Bosniak renal cyst classification, remains pertinent to the diagnosis
      and management of these difficult-to-diagnose complicated cystic masses.

PMID- 22357883
TI  - Impact of mammography detection on the course of breast cancer in women aged 40
      49 years.
AB  - PURPOSE: To analyze trends in detection method related to breast cancer stage at
      diagnosis, treatments, and outcomes over time among 40-49-year-old women.
      MATERIALS AND METHODS: i This study was institutional review board approved, with
      a waiver of informed consent, and HIPAA compliant. A longitudinal prospective
      cohort study was conducted of women aged 40-49 years who had primary breast
      cancer, during 1990-2008, and were identified and tracked by a dedicated registry
      database (n = 1977). Method of detection--patient detected (PtD), physician
      detected (PhysD), or mammography detected (MamD)--was chart abstracted. Disease
      specific survival and relapse-free survival statistics were calculated by using
      the Kaplan-Meier method for stage I-IV breast cancer. RESULTS: A significant
      increase in the percentage of MamD breast cancer over time (28%-58%) and a
      concurrent decline in patient and physician detected (Pt/PhysD) breast cancer
      (73%-42%) (Pearson x(2) = 72.72, P < .001) were observed over time from 1990 to
      2008, with an overall increase in lower-stage disease detection and a decrease in
      higher-stage disease. MamD breast cancer patients were more likely to undergo
      lumpectomy (67% vs 48% of Pt/PhysD breast cancer patients) and less likely to
      undergo modified radical mastectomy (25% vs 47% of the Pt/PhysD breast cancer
      patients) (P < .001). Uncorrected for stage, 13% of MamD breast cancer patients
      underwent surgery and chemotherapy versus 22% of Pt/PhysD breast cancer patients
      (P < .001), and 31% of MamD breast cancer patients underwent surgery, radiation
      therapy, and chemotherapy versus 59% of Pt/PhysD breast cancer patients (x(2) =
      305.13, P < .001). Analyzing invasive cancers only, 5-year relapse-free survival
      for MamD breast cancer patients was 92% versus 88% for Pt/PhysD patients (log
      rank test, 12.47; P < .001). CONCLUSION: Increased mammography-detected breast
      cancer over time coincided with lower-stage disease detection resulting in
      reduced treatment and lower rates of recurrence, adding factors to consider when
      evaluating the benefits of mammography screening of women aged 40-49 years.

PMID- 22357884
TI  - Systolic versus diastolic acquisition in myocardial perfusion MR imaging.
AB  - PURPOSE: To compare myocardial blood flow (MBF) at systole and diastole and
      determine the diagnostic accuracy of both phases in patients suspected of having
      coronary artery disease (CAD). MATERIALS AND METHODS: The study was approved by
      the regional ethics committee, and all patients gave written informed consent.
      After coronary angiography, 40 patients (27 men; mean age, 64 years +/- 8)
      underwent stress-rest perfusion magnetic resonance (MR) imaging at 1.5 T, with
      images aquired simultaneously at end systole and middiastole. Patients were
      classified as having CAD (stenosis .70%) or no significant CAD. In patients with
      CAD, myocardial segments were classified as stenosis-dependent (downstream of
      significant stenosis) or remote. MBF and myocardial perfusion reserve (MPR) were
      calculated for each segment, and mean values in each phase were compared with
      paired t tests. The diagnostic accuracy of each phase was determined with
      receiver operating characteristic (ROC) analysis. RESULTS: Twenty-one of the 40
      patients (53%) had CAD. Resting MBF was similar in both phases for patients with
      and patients without CAD (P > .05). Stress MBF was greater in diastole than
      systole in normal, remote, and stenosis-dependent segments (3.75 mL/g/min +/-
      1.50 vs 3.15 mL/g/min +/- 1.10, respectively, for normal segments; 2.75 mL/g/min
      +/- 1.20 vs 2.38 mL/g/min +/- 0.99, respectively, for remote segments; 2.49
      mL/g/min +/- 1.07 vs 2.23 mL/g/min +/- 0.90, respectively, for stenosis-dependent
      segments; P <.01). MPR was greater in diastole than systole in all segment groups
      (P < .05). The diagnostic accuracies at diastole and systole were similar (area
      under the ROC curve = 0.79 and 0.82, respectively; P = .30). CONCLUSION:
      Myocardial perfusion MR estimates of stress MBF and MPR were greater in diastole
      than systole in patients with and patients without CAD. However, both phases had
      similar diagnostic accuracy. These observations may be relevant to other dynamic
      perfusion methods, including computed tomography and echocardiography.

PMID- 22357886
TI  - Development of an intrabiliary MR imaging-monitored local agent delivery
      technique: a feasibility study in pigs.
AB  - PURPOSE: To investigate the feasibility of using magnetic resonance (MR) imaging
      to monitor intrabiliary delivery of motexafin gadolinium (MGd) into pig common
      bile duct (CBD) walls. MATERIALS AND METHODS: Animal studies were approved by the
      Institutional Animal Care and Use Committee. Initially, human cholangiocarcinoma
      cells were treated with various concentrations of MGd, a compound serving as a T1
      weighted MR imaging contrast agent, chemotherapy drug, and cell marker. These
      cells were then examined by means of confocal microscopy to confirm the
      intracellular uptake of MGd. In addition, an MGd/trypan blue mixture was locally
      infused into CBD walls of six cadaveric pigs using a microporous balloon
      catheter. CBDs of six pigs were infused with saline to serve as controls. Ex vivo
      T1-weighted MR imaging of these CBDs was performed. For in vivo technical
      validation, the microporous balloon catheter was placed in the CBD by means of a
      transcholecytic access to deliver MGd/trypan blue into CBD walls of six living
      pigs. T1-weighted images were obtained with both a surface coil and an
      intrabiliary MR imaging guidewire, and contrast-to-noise ratios of CBD walls
      before and after MGd/trypan blue infusions were compared in the two groups by
      means of paired t test, with subsequent histologic analysis to confirm the
      penetration and distribution of the MGd/trypan blue agent into CBD walls.
      RESULTS: In vitro experiments confirmed uptake of MGd by human cholangiocarcinoma
      cells. The ex vivo experiments demonstrated the penetration of MGd/trypan blue
      into the CBD walls. The in vivo experiment confirmed the uptake of MGd/trypan
      blue, showing an increased contrast-to-noise ratio for the CBD after
      administration of the mixture, compared with images obtained prior to MGd/trypan
      blue administration (11.6 +/- 4.2 [standard deviation] vs 5.7 +/- 2.8; P = .04).
      Histologic results depicted the blue dye stains and red fluorescence of MGd in
      CBD walls, confirming the imaging findings. CONCLUSION: It is feasible to use MR
      imaging to monitor the penetration of locally delivered MGd into pig CBD walls.

PMID- 22357885
TI  - Human hepatocellular carcinoma in a mouse model: assessment of tumor response to
      percutaneous ablation by using glyceraldehyde-3-phosphate dehydrogenase
      antagonists.
AB  - PURPOSE: To characterize tumor response to percutaneous injection of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antagonists in a mouse model of
      human hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Animal experiments
      were approved by the Johns Hopkins University Animal Care and Use Committee.
      Luciferase (luc) gene-expressing Hep3B tumor-bearing athymic nude mice were
      randomly divided into four groups of six mice each. Tumor-specific GAPDH
      inhibition was achieved by using percutaneous injection of GAPDH antagonists-3
      bromopyruvate (3-BrPA) or GAPDH-specific short hairpin RNA (shRNA). Tumor
      response to treatment was assessed by using bioluminescence imaging and analysis
      of GAPDH function and apoptotic markers (caspase-3, caspase-9, and positive
      staining for terminal deoxynucleotidyl transferase-mediated deoxyuridine 5
      triphospate nick end labeling). HCC samples from 34 patients were obtained from
      the Johns Hopkins tumor bank, as approved by the Institutional Review Board, for
      GAPDH expression analysis. Statistical analysis was performed by using a two
      sample t test or Spearman rank correlation coefficient. RESULTS: In vitro, 3-BrPA
      affected Hep3B cell viability (half maximal inhibitory concentration = 0.15
      mmol/L), and GAPDH shRNA suppressed (45.5%) colony formation. In vivo,
      percutaneous injection of GAPDH antagonists into luc-Hep3B tumors decreased
      bioluminescence imaging signal and viability (3-BrPA, P < .0001; GAPDH shRNA, P =
      .03). The 3-BrPA treatment primarily inhibited GAPDH activity (74.5%) compared
      with its expression (34.3%), whereas GAPDH shRNA inhibited both activity (60.6%)
      and expression (44.4%). Targeted inhibition of GAPDH by using 3-BrPA or shRNA
      induced apoptosis. HCC samples from patients demonstrated a strong correlation
      between GAPDH upregulation and the proto-oncogene c-jun expression (r = 0.543, P
      = .003). CONCLUSION: Percutaneous injection of GAPDH antagonists induces
      apoptosis and blocks Hep3B tumor progression, which demonstrates the therapeutic
      potential of targeting GAPDH in human HCC.

PMID- 22357887
TI  - Hepatic tumors: region-of-interest versus volumetric analysis for quantification
      of attenuation at CT.
AB  - PURPOSE: To evaluate the reproducibility of liver tumor attenuation measurement
      performed by using the routinely used manual region-of-interest (ROI) method and
      that of measurement performed by using a semiautomated volumetric approach at
      computed tomography (CT). MATERIALS AND METHODS: This HIPAA-compliant
      retrospective study had institutional review board approval. The requirement for
      patient informed consent was waived. Attenuation of colon cancer liver metastases
      in 208 patients was measured on portal venous phase multidetector CT images by
      using a single ROI, the average measurement in three ROIs on a single section,
      and with semiautomated segmentation of the entire tumor volume (volumetric
      attenuation) to evaluate intermethod agreement. Intraobserver and interobserver
      reproducibility were evaluated in the first 70 patients. Measurements were
      repeated after 30 days to assess intraobserver reproducibility. Differences
      between methods were tested by using repeated-measures analysis of variance.
      Intermethod, intraobserver, and interobserver agreements were tested by using
      Bland-Altman analysis and the Lin concordance correlation coefficient (rhoc). P <
      .05 was considered to indicate a significant difference. RESULTS: A total of 208
      pathologically proven colon cancer hepatic metastases larger than 20 mm in
      diameter in 100 women and 108 men (mean age, 61.6 years +/- 11.6 [standard
      deviation]; range, 28-87 years) were evaluated. Attenuation was significantly
      different between the three methods of measurement (P < .001 for all). Volumetric
      measurements had better intraobserver agreement (precision = 3.3%, rhoc = 0.996,
      P < .001) than single-ROI measurements (precision = 12.0%, rhoc = 0.947, P <
      .001) and measurements averaged over three ROIs (precision = 9.3%, rhoc = 0.965,
      P < .001). Volumetric measurements also had better interobserver agreement
      (precision = 3.6%, rhoc = 0.993, P < .001) than single-ROI measurements
      (precision = 11.3%, rhoc = 0.957, P < .001) and the average measurement in three
      ROIs (precision = 8.5%, rhoc = 0.976, P < .001). CONCLUSION: Measurements of
      hepatic tumor attenuation at multidetector CT are reproducible. An approach based
      on the evaluation of whole-lesion attenuation demonstrated better reproducibility
      than ROI measurements.

PMID- 22357888
TI  - Normal and altered three-dimensional portal venous hemodynamics in patients with
      liver cirrhosis.
AB  - PURPOSE: To compare time-resolved three-dimensional (3D) phase-contrast magnetic
      resonance (MR) imaging with three-directional velocity encoding (flow-sensitive
      four-dimensional [4D] MR imaging), with Doppler ultrasonography (US) as standard
      of reference, for investigating alterations in 3D portal venous hemodynamics in
      patients with liver cirrhosis compared with healthy age-matched control subjects
      and healthy young volunteers. MATERIAL & METHODS: This prospective study was
      approved by the local ethics committee, and written informed consent was obtained
      from all participants. Three-dimensional portal venous hemodynamics was assessed,
      employing flow-sensitive 4D MR imaging with a 3-T MR system (spatial resolution,
      approximately 2 mm(3); temporal resolution, approximately 45 msec) in 20 patients
      with hepatic cirrhosis, 20 healthy age-matched control subjects, and 21 healthy
      young volunteers. Flow characteristics were analyzed by using 3D streamlines and
      time-resolved particle traces. Quantitative analyses were performed by
      retrospectively evaluating regional peak and mean velocities, flow volume, and
      vessel area. Doppler US was used as standard of reference. Independent-sample t
      tests or Wilcoxon-Mann-Whitney tests were applied for comparing each subject
      group. Paired-sample t tests or Wilcoxon tests were applied when comparing MR
      imaging and US. RESULTS: Three-dimensional visualization of portal venous
      hemodynamics was successful, with complete visualization of the vessels in 18
      patients and 35 volunteers, with limitations in the left intrahepatic branches
      (87%, reader A; 89%, reader B). A moderate but significant correlation was
      observed between 4D MR imaging and Doppler US in nearly all maximum and mean
      velocities, flow volumes, and vessel areas (r = 0.24-0.64, P = .001-.044). With
      MR imaging, significant underestimation was observed of intrahepatic flow
      velocities and flow volumes, except vessel area, which Doppler US represented as
      even lower (P < .001 to P = .045). Six patients had collateralization with
      reopened umbilical vein, while one had flow reversal in the superior mesenteric
      vein visible at MR imaging only. CONCLUSION: Flow-sensitive 4D MR imaging may
      constitute a promising, alternative technique to Doppler US for evaluating
      hemodynamics in the portal venous system of patients with liver cirrhosis and may
      be a means of assessing pathologic changes in flow characteristics.

PMID- 22357889
TI  - Normal central zone of the prostate and central zone involvement by prostate
      cancer: clinical and MR imaging implications.
AB  - PURPOSE: To describe the anatomic features of the central zone of the prostate on
      T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) images and
      evaluate the diagnostic performance of MR imaging in detection of central zone
      involvement by prostate cancer. MATERIALS AND METHODS: The institutional review
      board waived informed consent and approved this retrospective, HIPAA-compliant
      study of 211 patients who underwent T2-weighted and DW MR imaging of the prostate
      before radical prostatectomy. Whole-mount step-section pathologic findings were
      the reference standard. Two radiologists independently recorded the visibility,
      MR signal intensity, size, and symmetry of the central zone and scored the
      likelihood of central zone involvement by cancer on T2-weighted MR images and on
      T2-weighted MR images plus apparent diffusion coefficient (ADC) maps generated
      from the DW MR images. Descriptive summary statistics were calculated for central
      zone imaging features. Sensitivity, specificity, and area under the curve were
      used to evaluate reader performance in detecting central zone involvement.
      RESULTS: For readers 1 and 2, the central zone was visible, at least partially,
      in 177 (84%) and 170 (81%) of 211 patients, respectively. The most common imaging
      appearance of the central zone was symmetric, homogeneous low signal intensity.
      Cancers involving the central zone had higher prostate-specific antigen values,
      Gleason scores, and rates of extracapsular extension and seminal vesicle invasion
      compared with cancers not involving the central zone (P < .05). Area under the
      curve, sensitivity, and specificity in detecting central zone involvement were
      0.70, 0.30, and 0.96 for reader 1 and 0.65, 0.35, and 0.93 for reader 2, and
      these values did not differ significantly between T2-weighted imaging and T2
      weighted imaging plus ADC maps. CONCLUSION: The central zone was visualized in
      most patients. Cancers involving the central zone were associated with more
      aggressive disease than those without central zone involvement.

PMID- 22357890
TI  - Preoperative detection and localization of accessory pudendal artery with
      contrast-enhanced MR angiography.
AB  - PURPOSE: To evaluate the diagnostic performance of contrast material-enhanced
      magnetic resonance (MR) angiography for preoperative detection and localization
      of accessory pudendal arteries (APAs) in patients with prostate cancer. MATERIALS
      AND METHODS: This prospective study was approved by the institutional review
      board, and informed consent was obtained. Between July 2007 and December 2010,
      127 patients underwent contrast-enhanced MR angiography following prostate MR
      imaging at 3.0 T before robot-assisted laparoscopic radical prostatectomy (RALP).
      APAs were defined as any arteries located in the periprostatic region and
      anastomosed with the common penile artery or its branches; they were then
      subclassified into lateral and apical APAs. For detecting and localizing APAs, MR
      angiograms were evaluated prospectively by one reader and retrospectively by two
      independent blinded readers. Diagnostic performance was determined on a per
      patient basis by using surgical findings as the reference standard. In addition,
      the origin of APAs identified at both surgery and contrast-enhanced MR
      angiography was determined by consensus of two retrospective readers. Interreader
      agreements were assessed by using k statistics. RESULTS: At surgery, 19 APAs
      (seven right apical, three left apical, four right lateral, and five left
      lateral) were detected in 16 patients, and 16 of these APAs were localized in 13
      patients at preoperative contrast-enhanced MR angiography. Prospectively,
      sensitivity, specificity, and accuracy of contrast-enhanced MR angiography for
      the localization of APAs were 81.3%, 93.7%, and 92.1%, while retrospectively they
      were 87.5%, 91.9%, and 91.3% for reader 2 and 75.0%, 90.1%, and 88.2% for reader
      3, respectively. Overall interreader agreement was substantial (k = 0.795). Nine
      and seven APAs originated from the obturator artery and the inferior vesical
      artery, respectively. CONCLUSION: Contrast-enhanced MR angiography can be used
      for the preoperative detection of APAs in patients with prostate cancer.

PMID- 22357891
TI  - Micro-MR imaging-based computational biomechanics demonstrates reduction in
      cortical and trabecular bone strength after renal transplantation.
AB  - PURPOSE: To examine the ability of three-dimensional micro-magnetic resonance
      (MR) imaging-based computational biomechanics to detect mechanical alterations in
      trabecular bone and cortical bone in the distal tibia of incident renal
      transplant recipients 6 months after renal transplantation and compare them with
      bone mineral density (BMD) outcomes. MATERIALS AND METHODS: The study was
      approved by the institutional review board and complied with HIPAA guidelines.
      Written informed consent was obtained from all subjects. Micro-MR imaging of
      distal tibial metaphysis was performed within 2 weeks after renal transplantation
      (baseline) and 6 months later in 49 participants (24 female; median age, 44
      years; range, 19-61 years) with a clinical 1.5-T whole-body imager using a
      modified three-dimensional fast large-angle spin-echo pulse sequence. Micro
      finite-element models for cortical bone, trabecular bone, and whole-bone section
      were generated from each image by delineating the endosteal and periosteal
      boundaries. Mechanical parameters (stiffness and failure load) were estimated
      with simulated uniaxial compression tests on the micro-finite-element models.
      Structural parameters (trabecular bone volume fraction [BV/TV, bone volume to
      total volume ratio], trabecular thickness [TbTh], and cortical thickness [CtTh])
      were computed from micro-MR images. Total hip and spine areal BMD were determined
      with dual-energy x-ray absorptiometry (DXA). Parameters obtained at the follow-up
      were compared with the baseline values by using parametric or nonparametric tests
      depending on the normality of data. RESULTS: All mechanical parameters were
      significantly lower at 6 months compared with baseline. Decreases in cortical
      bone, trabecular bone, and whole-bone stiffness were 3.7% (P = .03), 4.9% (P =
      .03), and 4.3% (P = .003), respectively. Decreases in cortical bone, trabecular
      bone, and whole-bone failure strength were 7.6% (P = .0003), 6.0% (P = .004), and
      5.6% (P = .0004), respectively. Conventional structural measures, BV/TV, TbTh,
      and CtTh, did not change significantly. Spine BMD decreased by 2.9% (P < .0001),
      while hip BMD did not change significantly at DXA. CONCLUSION: MR imaging-based
      micro-finite-element analysis suggests that stiffness and failure strength of the
      distal tibia decrease over a 6-month interval after renal transplantation.

PMID- 22357892
TI  - Multiple sclerosis: effects of cognitive rehabilitation on structural and
      functional MR imaging measures--an explorative study.
AB  - PURPOSE: To evaluate brain changes after cognitive rehabilitation in patients
      with clinically stable relapsing-remitting (RR) multiple sclerosis (MS) by using
      neuropsychologic assessment and structural and functional magnetic resonance (MR)
      imaging techniques. MATERIALS AND METHODS: The study was conducted with approval
      of the involved institutional review boards. Written informed consent was
      obtained from each participant. Twenty patients with RR MS and cognitive deficits
      at baseline were randomly assigned to undergo treatment (n = 10), which entailed
      computer-assisted cognitive rehabilitation of attention and information
      processing and executive functions, or to serve as a control subjects (n = 10)
      without cognitive rehabilitation. All patients underwent a standardized
      neuropsychologic assessment and MR imaging at baseline and after 12 weeks.
      Changes in gray matter (GM) volumes on three-dimensional T1-weighted images and
      changes in normal-appearing white matter (NAWM) architecture on diffusion
      weighted images were assessed. Changes in functional activity at functional MR
      imaging during the Stroop task and at rest were also investigated by using linear
      models. RESULTS: As compared with their performance at baseline, the patients in
      the treatment group improved at tests of attention and information processing and
      executive functions. Neither structural modifications to GM volume nor
      modifications to NAWM architecture were detected at follow-up in both groups.
      Functional MR imaging demonstrated modifications of the activity of the posterior
      cingulate cortex (PCC)/precuneus and dorsolateral prefrontal cortex (PFC) during
      the Stroop task, as well as modifications of the activity of the anterior
      cingulum, PCC and/or precuneus, left dorsolateral PFC, and right inferior
      parietal lobule at rest in the treatment group compared with the control group.
      In the treatment group, functional MR imaging changes were correlated with
      cognitive improvement (P < .0001 to .01). CONCLUSION: Rehabilitation of attention
      and information processing and executive functions in RR MS may be effected
      through enhanced recruitment of brain networks subserving the trained functions.

PMID- 22357893
TI  - Lumbar MR imaging and reporting epidemiology: do epidemiologic data in reports
      affect clinical management?
AB  - PURPOSE: To retrospectively examine the association between the inclusion of
      epidemiologic information in lumbar spine magnetic resonance (MR) imaging reports
      regarding findings in asymptomatic individuals and the rates of subsequent cross
      sectional imaging and treatments in patients with low back pain or radiculopathy
      referred for imaging by primary care providers. MATERIALS AND METHODS:
      Institutional review board approval was received for a retrospective chart
      review, with waiver of informed consent and HIPAA authorization. During 3 years,
      an epidemiologic statement was routinely but arbitrarily included in lumbar spine
      MR imaging reports. Two hundred thirty-seven reports documenting uncomplicated
      degenerative changes on initial lumbar spine MR images were identified, 71 (30%)
      of which included the statement (statement group) and 166 (70%) did not
      (nonstatement group). The rates of repeat cross-sectional imaging and treatments
      within 1 year were compared between groups by using logistic regression
      controlling for severity of MR imaging findings. RESULTS: Patients in the
      statement group were significantly less likely to receive a prescription for
      narcotics for their symptoms than patients in the nonstatement group (odds ratio
      = 0.29, P = .01). Repeat cross-sectional imaging and physical therapy referrals
      were also less common in the statement group than in the nonstatement group (odds
      ratio = 0.22 and 0.55, respectively), but these differences were not
      statistically significant (P = .14 and .06, respectively). Rates of steroid
      injections, surgical consultations, and surgeries were similar between groups.
      CONCLUSION: Patients were less likely to receive narcotics prescriptions from
      primary care providers when epidemiologic information was included in their
      lumbar spine MR imaging reports.

PMID- 22357894
TI  - Multiple sclerosis: cerebral circulation time.
AB  - PURPOSE: To assess cerebral circulation times (CCTs) in patients with multiple
      sclerosis (MS) and control subjects by using contrast material-enhanced
      ultrasonography (US) to determine whether vascular abnormalities can be detected
      in this disease. MATERIALS AND METHODS: This study was approved by the local
      ethics committee, and informed consent was obtained from all subjects. One
      hundred three patients with MS and 42 control subjects underwent extracranial and
      transcranial venous echo-color Doppler ultrasonography (US) and contrast-enhanced
      US. CCT was defined as the difference in arrival time of the US contrast agent
      bolus between the carotid artery and the internal jugular vein. The presence of
      chronic cerebrospinal venous insufficiency (CCSVI) was defined according to
      previously reported criteria for the extracranial and transcranial US techniques.
      Nonparametric statistics, including the Mann-Whitney U test and the Kruskal
      Wallis analysis of variance, were used to compare contrast-enhanced US parameters
      between groups. RESULTS: The longest and average CCTs were substantially
      prolonged in patients with MS compared with those in control subjects (median
      longest CCT in patients with MS, 6.47 seconds [range, 3.29-29.24 seconds]; that
      in control subjects, 5.54 seconds [range, 2.57-7.63 seconds]; P < .001; median
      average CCT in patients with MS, 5.76 seconds [range, 2.64-17.51 seconds]; that
      in control subjects, 5.01 seconds [range, 2.57-7.06 seconds]; P < .002). No
      correlation was found between CCTs and clinical parameters. The prevalence of
      CCSVI was higher in patients with MS than in control subjects (77% vs 28%, P <
      .0001). CCT was not significantly different between patients with MS who had
      CCSVI and patients with MS who did not (P = .182). CONCLUSION: These results
      suggest that contrast-enhanced US with CCT assessment may have a role in the
      evaluation of cerebral blood flow in patients with MS and that a vascular
      impairment could be associated with MS. The finding of a prolonged CCT at
      contrast-enhanced US does not result from outflow impairment. Further studies are
      required to verify these observations and to clarify if CCT and CCSVI have any
      physiologic and clinical relevance in MS.

PMID- 22357895
TI  - Pediatric nonlymphoblastic non-Hodgkin lymphoma: baseline, interim, and
      posttreatment PET/CT versus contrast-enhanced CT for evaluation--a prospective
      study.
AB  - PURPOSE: To prospectively examine the roles of positron emission tomography
      (PET)/computed tomography (CT) and conventional contrast material-enhanced CT at
      baseline, after two cycles of chemotherapy, and after completion of chemotherapy
      in pediatric patients with nonlymphoblastic non-Hodgkin lymphoma (NHL) who were
      treated with similar standard treatment protocols. MATERIALS AND METHODS: The
      institutional ethics committee approved the study protocol, and all patients were
      enrolled after written informed consent was obtained. Patients with
      nonlymphoblastic NHL were prospectively enrolled between January 2008 and March
      2010. Patients underwent contrast-enhanced CT and PET/CT for staging and for
      response assessment after two cycles of chemotherapy (interim) and treatment
      completion. Complete metabolic response versus no metabolic response at PET/CT
      and complete response versus no complete response at contrast-enhanced CT was
      analyzed by using Kaplan-Meier survival analysis. RESULTS: The final study
      included 34 patients with nonlymphoblastic NHL (median age, 10.5 years). Baseline
      PET/CT and contrast-enhanced CT showed concordance in depiction of 112 disease
      sites; PET/CT depicted 18 more disease sites and two fewer disease sites than
      contrast-enhanced CT (P = .0003). Disease in five of 34 patients was upstaged,
      and disease in no patient was downstaged at PET/CT. There was 100% (four of four)
      concordance between bone marrow involvement at biopsy and stage at PET/CT. The
      median length of follow-up was 20.3 months. Response at interim PET/CT and
      contrast-enhanced CT could not predict progression-free survival (PFS) (P = .083
      and .18, respectively) or overall survival (OS) (P = .159 and.08, respectively).
      Posttreatment PET/CT and contrast-enhanced CT findings could predict PFS (P =
      .036 and .002, respectively) and posttreatment contrast-enhanced CT findings
      could predict OS (P = .035); however, posttreatment PET/CT findings could not
      predict OS (P = .067). CONCLUSION: PET/CT depicts additional sites compared with
      contrast-enhanced CT and results in upstaging of disease. Either PET/CT or
      contrast-enhanced CT may be used for response assessment and prognostication in
      stage III or IV nonlymphoblastic pediatric NHL.

PMID- 22357896
TI  - Three-section expiratory CT: insufficient for trapped air assessment in patients
      with cystic fibrosis?
AB  - PURPOSE: To estimate the effect of the number of computed tomography (CT)
      sections on trapped air (TA) assessment in patients with cystic fibrosis (CF) by
      using an established scoring system and a new quantitative scoring system and to
      compare CT and pulmonary function test (PFT) estimates of TA in a cross-sectional
      and longitudinal study. MATERIALS AND METHODS: In this institutional review board
      approved pilot study, 20 subjects aged 6-20 years (12 female and eight male;
      median age, 12.6 years) contributed two expiratory CT studies (three-section
      baseline CT, volumetric follow-up CT) and two PFT studies over 2 years after
      parental informed consent was obtained. From follow-up CT studies, seven sets
      were composed: Set 1 was volumetric. Sets 2, 3, 4, and 5, had spacing of 2.4,
      4.8, 9.6, and 20.4 mm, respectively, between sections. Sets 6 and 7 contained
      five and three sections, respectively. Longitudinal follow-up was performed with
      three sections. All images were deidentified and randomized, and TA was scored
      with the Brody II system and a new quantitative system. Statistical analysis
      included the Wilcoxon signed rank test, calculation of Spearman and intraclass
      correlation coefficients, and use of three-section and linear mixed models.
      RESULTS: For the Brody II system, the intraclass correlation coefficient for set
      1 versus those for sets 2 through 7 was 0.75 versus 0.87; however, mean scores
      from sets 6 and 7 were significantly lower than the mean score from set 1 (P =
      .01 and P < .001, respectively). For the quantitative system, the number of
      sections did not affect TA assessment (intraclass correlation coefficient range,
      0.82-0.88; P > .13 for all). CT and PFT estimates were not correlated (r(s) =
      20.19 to 0.09, P = .43-.93). No change in TA over time was found for CT or PFT (P
      > .16 for all). CONCLUSION: The number of sections affected Brody II estimates,
      suggesting that three-section protocols lead to underestimation of TA assessment
      in patients with CF when using the Brody II system; CT and PFT estimates of TA
      showed no correlation and no significant change over time.

PMID- 22357897
TI  - Using radiation risk models in cancer screening simulations: important
      assumptions and effects on outcome projections.
AB  - PURPOSE: To evaluate the effect of incorporating radiation risk into
      microsimulation (first-order Monte Carlo) models for breast and lung cancer
      screening to illustrate effects of including radiation risk on patient outcome
      projections. MATERIALS AND METHODS: All data used in this study were derived from
      publicly available or deidentified human subject data. Institutional review board
      approval was not required. The challenges of incorporating radiation risk into
      simulation models are illustrated with two cancer screening models (Breast Cancer
      Model and Lung Cancer Policy Model) adapted to include radiation exposure effects
      from mammography and chest computed tomography (CT), respectively. The primary
      outcome projected by the breast model was life expectancy (LE) for BRCA1 mutation
      carriers. Digital mammographic screening beginning at ages 25, 30, 35, and 40
      years was evaluated in the context of screenings with false-positive results and
      radiation exposure effects. The primary outcome of the lung model was lung cancer
      specific mortality reduction due to annual screening, comparing two diagnostic CT
      protocols for lung nodule evaluation. The Metropolis-Hastings algorithm was used
      to estimate the mean values of the results with 95% uncertainty intervals (UIs).
      RESULTS: Without radiation exposure effects, the breast model indicated that
      annual digital mammography starting at age 25 years maximized LE (72.03 years;
      95% UI: 72.01 years, 72.05 years) and had the highest number of screenings with
      false-positive results (2.0 per woman). When radiation effects were included,
      annual digital mammography beginning at age 30 years maximized LE (71.90 years;
      95% UI: 71.87 years, 71.94 years) with a lower number of screenings with false
      positive results (1.4 per woman). For annual chest CT screening of 50-year-old
      females with no follow-up for nodules smaller than 4 mm in diameter, the lung
      model predicted lung cancer-specific mortality reduction of 21.50% (95% UI:
      20.90%, 22.10%) without radiation risk and 17.75% (95% UI: 16.97%, 18.41%) with
      radiation risk. CONCLUSION: Because including radiation exposure risk can
      influence long-term projections from simulation models, it is important to
      include these risks when conducting modeling-based assessments of diagnostic
      imaging.

PMID- 22357898
TI  - Compressive sensing could accelerate 1H MR metabolic imaging in the clinic.
AB  - PURPOSE: To retrospectively evaluate the fidelity of magnetic resonance (MR)
      spectroscopic imaging data preservation at a range of accelerations by using
      compressed sensing. MATERIALS AND METHODS: The protocols were approved by the
      institutional review board of the university, and written informed consent to
      acquire and analyze MR spectroscopic imaging data was obtained from the subjects
      prior to the acquisitions. This study was HIPAA compliant. Retrospective
      application of compressed sensing was performed on 10 clinical MR spectroscopic
      imaging data sets, yielding 600 voxels from six normal brain data sets, 163
      voxels from two brain tumor data sets, and 36 voxels from two prostate cancer
      data sets for analysis. The reconstructions were performed at acceleration
      factors of two, three, four, five, and 10 and were evaluated by using the root
      mean square error (RMSE) metric, metabolite maps (choline, creatine, N
      acetylaspartate [NAA], and/or citrate), and statistical analysis involving a
      voxelwise paired t test and one-way analysis of variance for metabolite maps and
      ratios for comparison of the accelerated reconstruction with the original case.
      RESULTS: The reconstructions showed high fidelity for accelerations up to 10 as
      determined by the low RMSE (< 0.05). Similar means of the metabolite intensities
      and hot-spot localization on metabolite maps were observed up to a factor of
      five, with lack of statistically significant differences compared with the
      original data. The metabolite ratios of choline to NAA and choline plus creatine
      to citrate did not show significant differences from the original data for up to
      an acceleration factor of five in all cases and up to that of 10 for some cases.
      CONCLUSION: A reduction of acquisition time by up to 80%, with negligible loss of
      information as evaluated with clinically relevant metrics, has been successfully
      demonstrated for hydrogen 1 MR spectroscopic imaging.

PMID- 22357899
TI  - Generalized multiple-layer appearance of the cerebral cortex with 3D FLAIR 7.0-T
      MR imaging.
AB  - To examine the multiple-layer appearance of the cerebral cortex with fluid
      attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging at 7.0 T,
      whole-brain volumetric three-dimensional (3D) magnetization prepared FLAIR images
      were acquired in 12 volunteers (0.8 3 0.8 3 0.8-mm spatial resolution). Signal
      intensity profiles were evaluated for the anterior frontal (Brodmann area [BA]
      10), posterior frontal (BA 6), parietal (BA 7), precentral (BA 4), postcentral
      (BA 3), occipital (BA 18), and calcarine (BA 17) regions. Variance of the
      normalized profile was used as the metric for the multiple-layer appearance.
      Wilcoxon signed-rank tests were performed to compare variances of the profiles
      between all areas. All cortical areas showed multiple-layered appearances, with a
      prominent hyperintense band at the external surface of the cortex, a hypointense
      band deeper in the cortex, and a hyperintense third band. The ranking from least-
      to most-pronounced layer appearance was as follows: postcentral (variance, 0.04),
      posterior frontal (variance, 0.05), calcarine (variance, 0.05), precentral
      (variance, 0.06), parietal (variance, 0.08), anterior frontal (variance, 0.10),
      and occipital (variance, 0.11). Each region was significantly different from at
      least one other region. In conclusion, a multiple-layer appearance of the
      cerebral cortex was found for all cortical regions with high-spatial-resolution
      3D FLAIR MR imaging at 7.0 T.

PMID- 22357900
TI  - Diagnostic performance of gray-scale US and elastography in solid thyroid
      nodules.
AB  - PURPOSE: To evaluate the diagnostic performance of gray-scale ultrasonography
      (US) and elastography in differentiating benign and malignant thyroid nodules.
      MATERIALS AND METHODS: This was an institutional review board-approved
      retrospective study with waiver of informed consent. A total of 703 solid thyroid
      nodules in 676 patients (mean age, 49.7 years; range, 18-79 years) were included;
      there were 556 women (mean age, 49.5 years; range, 20-74 years) and 120 men (mean
      age, 50.7 years; range, 18-79 years). Nodules with marked hypoechogenicity,
      poorly defined margins, microcalcifications, and a taller-than-wide shape were
      classified as suspicious at grayscale US. Findings at elastography were
      classified according to the Rago criteria and the Asteria criteria. The
      diagnostic performances of gray-scale US and elastography were compared. For
      comparison between the diagnostic performances of gray-scale US and the
      combination of gray-scale US and elastography, three sets of criteria were
      assigned: criteria set 1, nodules with any suspicious grayscale US feature were
      assessed as suspicious; criteria set 2, Rago criteria were added as suspicious
      features to criteria set 1; and criteria set 3, Asteria criteria were added as
      suspicious features to criteria set 1. The diagnostic performances of gray-scale
      US, elastography with Rago criteria, and elastography with Asteria criteria, and
      odds ratios (ORs) with 95% confidence intervals for predicting thyroid malignancy
      were compared using generalized estimating equation analysis. RESULTS: Of 703
      nodules, 217 were malignant and 486 were benign. Sensitivity, negative predictive
      value (NPV), and OR of gray-scale US for the 703 nodules were 91.7%, 94.7%, and
      22.1, respectively, and these values were higher than the 15.7% and 65.4%
      sensitivity, 71.7% and 79.1% NPV, and 3.7 and 2.6 ORs found for elastography with
      Rago and Asteria criteria, respectively. Specificity, positive predictive value,
      and accuracy for criteria set 1 were significantly higher than those for criteria
      sets 2 and 3 for most of the nodule subgroups that were considered. CONCLUSION:
      Elastography alone, as well as the combination of elastography and gray-scale US,
      showed inferior performance in the differentiation of malignant and benign
      thyroid nodules compared with gray-scale US features; elastography was not a
      useful tool in recommending fine-needle aspiration biopsy.

PMID- 22357901
TI  - Liver cancer: effects, safety, and cost-effectiveness of controlled-release
      oxycodone for pain control after TACE.
AB  - PURPOSE: To evaluate the analgesic effect, safety, and cost-effectiveness of
      controlled-release oxycodone (CRO) to control postoperative pain in patients with
      liver cancer who are undergoing transarterial chemoembolization. MATERIALS AND
      METHODS: This randomized, double-blind, placebo-controlled, prospective clinical
      study received institutional review board approval. After written informed
      consent was obtained, 210 patients with liver cancer were randomized into three
      groups of 70 patients. Group 1 received 20 mg of CRO, group 2 received 10 mg of
      CRO, and group 3 received a placebo at 1 hour before transarterial
      chemoembolization (T(0)) and 12 (T(12)) and 24 (T(24)) hours after T(0). Pain
      intensity on a numeric rating scale, percentage of patients with each degree of
      pain, quality of life, adverse reactions, analgesic costs, and hospital stays
      were evaluated and compared among the three groups. RESULTS: Numeric rating scale
      scores for pain intensity in group 1 and group 2 were significantly lower than
      those in group 3 at T(0-12) (P < .001); T(12-24) (P < .001); and T(24-48) (P <
      .001). When group 1 with group 2 were compared, numeric rating scale scores were
      significantly lower in group 1 than in group 2 during the period of T(0-12) (P <
      .001) but were not significantly different at T(12-24) (P = .68) and T(24-48) (P
      = .10). Analgesic cost and hospital stay were significantly lower in treated
      groups than in the placebo group. No significant difference was observed in
      quality of life and adverse events between the treated groups and the placebo
      group. CONCLUSION: CRO is effective, safe, and cost-effective in the control of
      postoperative pain after transarterial chemoembolization for patients with
      inoperable liver cancer.

PMID- 22357902
TI  - Radiofrequency ablation versus hepatic resection for the treatment of
      hepatocellular carcinomas 2 cm or smaller: a retrospective comparative study.
AB  - PURPOSE: To compare retrospectively the effects of percutaneous radiofrequency
      (RF) ablation with those of hepatic resection in the treatment of hepatocellular
      carcinoma (HCC) measuring 2 cm or smaller. MATERIALS AND METHODS: This study was
      approved by the institutional ethics committee, and all patients provided written
      informed consent before treatment. From December 2003 to December 2008, 145
      patients with a resectable HCC measuring 2 cm or smaller were studied. Sixty-six
      patients had a central HCC (located at least 3 cm from the liver capsule). As an
      initial treatment, 71 patients were treated with percutaneous RF ablation and 74
      with surgical resection. Of the patients with central HCC, 37 underwent
      percutaneous RF ablation and 29 underwent surgical resection. Survival curves
      were constructed with the Kaplan-Meier method and compared by using the log-rank
      test. The relative prognostic significance of the variables for predicting
      overall survival rates was assessed with multivariate Cox proportional hazards
      regression analysis. Complications were observed clinically when patients were
      admitted and assessed by telephone interview after patients were discharged.
      RESULTS: One death was considered to be related to treatment after surgical
      resection. Major complications occurred significantly more often in the surgical
      resection group (38 of 74 patients) than in the RF ablation group (14 of 71
      patients) (P = .009). The 1-, 3-, and 5-year overall survival rates were 98.5%,
      87.7%, and 71.9%, respectively, with RF ablation and 90.5%, 70.9%, and 62.1% with
      surgical resection (P = .048). The corresponding recurrence-free survival rates
      were 76.4%, 65.2%, and 59.8% with RF ablation and 75.6%, 56.1%, and 51.3% with
      surgical resection (P = .548). At subgroup analysis of patients with central HCC,
      1-, 3-, and 5-year overall survival rates were 96.6%, 93.0%, and 79.9% with RF
      ablation and 92.0%, 71.6%, and 61.5% with surgical resection (P = .020). The
      corresponding recurrence-free survival rates were 86.5%, 74.0%, and 67.0% with RF
      ablation and 68.0%, 40.0%, and 40.0% with surgical resection (P = .033). For
      patients with peripheral HCC, 1-, 3-, and 5-year overall survival rates were
      97.3%, 83.3%, and 65.1% with RF ablation and 87.8%, 68.4%, and 62.9% with
      surgical resection (P = .464). The corresponding recurrence-free survival rates
      were 68.7%, 59.2%, and 54.9% with RF ablation and 82.9%, 66.6%, and 52.9% with
      surgical resection (P = .351). CONCLUSION: The efficacy and safety of
      percutaneous RF ablation were better than those of surgical resection in patients
      with HCC measuring 2 cm or smaller, especially those with central HCC.

PMID- 22357904
TI  - Case 179: Hereditary hemochromatosis.

PMID- 22357905
TI  - Parturient Montes.

PMID- 22357906
TI  - Color and power Doppler US for diagnosing Carpal tunnel syndrome and determining
      its severity.

PMID- 22357907
TI  - Detection of small (<=20 mm) pancreatic adenocarcinoma: histologic grading and CT
      enhancement features.

PMID- 22357908
TI  - Utility of high-spatial-resolution gray-scale US in characterizing nonstenotic
      plaque.

PMID- 22357910
TI  - RNA binding is more critical to the suppression of silencing function of Cucumber
      mosaic virus 2b protein than nuclear localization.
AB  - Previously, we found that silencing suppression by the 2b protein and six mutants
      correlated both with their ability to bind to double-stranded (ds) small RNAs
      (sRNAs) in vitro and with their nuclear/nucleolar localization. To further
      discern the contribution to suppression activity of sRNA binding and of nuclear
      localization, we have characterized the kinetics of in vitro binding to a ds
      sRNA, a single-stranded (ss) sRNA, and a micro RNA (miRNA) of the native 2b
      protein and eight mutant variants. We have also added a nuclear export signal
      (NES) to the 2b protein and assessed how it affected subcellular distribution and
      suppressor activity. We found that in solution native protein bound ds siRNA,
      miRNA, and ss sRNA with high affinity, at protein:RNA molar ratios ~2:1. Of the
      four mutants that retained suppressor activity, three showed sRNA binding
      profiles similar to those of the native protein, whereas the remaining one bound
      ss sRNA at a 2:1 molar ratio, but both ds sRNAs with 1.5-2 times slightly lower
      affinity. Three of the four mutants lacking suppressor activity failed to bind to
      any sRNA, whereas the remaining one bound them at far higher ratios. NES-tagged
      2b protein became cytoplasmic, but suppression activity in patch assays remained
      unaffected. These results support binding to sRNAs at molar ratios at or near 2:1
      as critical to the suppressor activity of the 2b protein. They also show that
      cytoplasmically localized 2b protein retained suppressor activity, and that a
      sustained nuclear localization was not required for this function.

PMID- 22357911
TI  - Conservation of the relative tRNA composition in healthy and cancerous tissues.
AB  - Elongation in protein translation is strongly dependent on the availability of
      mature transfer RNAs (tRNAs). The relative concentrations of the tRNA
      isoacceptors determine the translation efficiency in unicellular organisms.
      However, the degree of correspondence of codons and the relevant tRNA
      isoacceptors serves as an estimator for translation efficiency in all organisms.
      In this study, we focus on the translational capacity of the human proteome. We
      show that the correspondence between the codon usage and tRNAs can be improved by
      combining experimental measurements with the genomic copy number of isoacceptor
      groups. We show that there are technologies of tRNA measurements that are useful
      for our analysis. However, fragments of tRNAs do not agree with translational
      capacity. It was shown that there is a significant increase in the absolute
      levels of tRNA genes in cancerous cells in comparison to healthy cells. However,
      we find that the relative composition of tRNA isoacceptors in healthy, cancerous,
      or transformed cells remains almost identical. This result may indicate that
      maintaining the relative tRNA composition in cancerous cells is advantageous via
      its stabilizing of the effectiveness of translation.

PMID- 22357912
TI  - Transcription regulates telomere dynamics in human cancer cells.
AB  - Telomeres are nucleoprotein structures capping the physical ends of linear
      eukaryotic chromosomes. Although largely heterochromatic, telomeres are
      transcribed into telomeric repeat-containing RNA (TERRA) molecules by RNA
      polymerase II. The functions associated with telomere transcription and TERRA
      remain ill defined. Here we show that the transcriptional activity of human
      telomeres directly regulates their movement during interphase. We find that
      chemical inhibition of global transcription dampens telomere motion, while global
      stimulation promotes it. Likewise, when DNA methyltransferase enzymes are deleted
      to augment telomere transcription, we observe increased telomere movement.
      Finally, using a cell line engineered with a unique transcriptionally inducible
      telomere, we show that transcription of one specific telomere stimulates only its
      own dynamics without overtly affecting its stability or its length. We reveal a
      new and unforeseen function for telomere transcription as a regulator of telomere
      motion, and speculate on the intriguing possibility that transcription-dependent
      telomere motion sustains the maintenance of functional and dysfunctional
      telomeres.

PMID- 22357909
TI  - Ultrastructure of synapses in the mammalian brain.
AB  - The morphology and molecular composition of synapses provide the structural basis
      for synaptic function. This article reviews the electron microscopy of excitatory
      synapses on dendritic spines, using data from rodent hippocampus, cerebral
      cortex, and cerebellar cortex. Excitatory synapses have a prominent postsynaptic
      density, in contrast with inhibitory synapses, which have less dense presynaptic
      or postsynaptic specializations and are usually found on the cell body or
      proximal dendritic shaft. Immunogold labeling shows that the presynaptic active
      zone provides a scaffold for key molecules involved in the release of
      neurotransmitter, whereas the postsynaptic density contains ligand-gated ionic
      channels, other receptors, and a complex network of signaling molecules.
      Delineating the structure and molecular organization of these axospinous synapses
      represents a crucial step toward understanding the mechanisms that underlie
      synaptic transmission and the dynamic modulation of neurotransmission associated
      with short- and long-term synaptic plasticity.

PMID- 22357913
TI  - Connecting tubule glomerular feedback mediates acute tubuloglomerular feedback
      resetting.
AB  - Tubuloglomerular feedback (TGF) and connecting tubule glomerular feedback (CTGF)
      are mechanisms that control afferent arteriole (Af-Art) tone. TGF, initiated by
      increased NaCl at the macula densa, causes Af-Art constriction. Prolonged
      activation of TGF leads to an attenuation or "resetting" of its constrictor
      effect. The mechanisms of TGF resetting remain incompletely understood. CTGF is
      initiated by increased NaCl in the connecting tubule and Na(+) entry via
      epithelial sodium channels (ENaC). Contrary to TGF, CTGF dilates the Af-Art.
      Here, we hypothesize that CTGF, in part, mediates TGF resetting. We performed
      micropuncture of individual rat nephrons while measuring stop-flow pressure
      (P(SF)), an index of glomerular filtration pressure and Af-Art tone. Increases in
      Af-Art tone cause P(SF) to decrease. TGF responses, measured as the decrease in
      P(SF) induced by switching late proximal tubule perfusion from 5 to 40 nl/min,
      were elicited before and after a 30-min period of sustained perfusion of the late
      proximal tubule at a rate of 40 nl/min designed to induce TGF resetting. TGF
      responses were 7.3 +/- 0.3 and 4.9 +/- 0.2 mmHg before and after resetting was
      induced (P < 0.001, n = 6). When CTGF was inhibited with the ENaC blocker
      benzamil (1 MUM), TGF responses were 9.5 +/- 0.3 and 8.8 +/- 0.6 mmHg (NS, n =
      6), thus resetting was abolished. In the presence of the carbonic anhydrase
      inhibitor acetazolamide (10 mM), TGF responses were 8.8 +/- 0.6 and 3.3 +/- 0.4
      mmHg before and after resetting (P < 0.001, n = 6). With both acetazolamide and
      benzamil, TGF responses were 10.4 +/- 0.2 and 8.4 +/- 0.5 mmHg (P < 0.01, n = 6),
      thus resetting was attenuated. We conclude that CTGF, in part, mediates acutely
      induced TGF resetting.

PMID- 22357914
TI  - Role of blood pressure in mediating the influence of salt intake on renin
      expression in the kidney.
AB  - The salt intake of an organism controls the number of renin-producing cells in
      the kidney by yet undefined mechanisms. This study aimed to assess a possible
      mediator role of preglomerular blood pressure in the control of renin expression
      by oral salt intake. We used wild-type (WT) mice and mice lacking angiotensin II
      type 1a receptors (AT(1a)-/-) displaying an enhanced salt sensitivity to renin
      expression. In WT kidneys, we found renin-expressing cells at the ends of all
      afferent arterioles. A low-salt diet (0.02%) led to a moderate twofold increase
      in renin-expressing cells along afferent arterioles. In AT(1a)-/- mice, lowering
      of salt content led to a 12-fold increase in renin expression. Here, the renin
      expressing cells were distributed along the preglomerular vascular tree in a
      typical distal-to-proximal distribution gradient which was most prominent at high
      salt intake and was obliterated at low salt intake by the appearance of renin
      expressing cells in proximal parts of the preglomerular vasculature. While
      lowering of salt intake produced only a small drop in blood pressure in WT mice,
      the marked reduction of systolic blood pressure in AT(1a)-/- mice was accompanied
      by the disappearance of the distribution gradient from afferent arterioles to
      arcuate arteries. Unilateral renal artery stenosis in AT(1a)-/- mice on a normal
      salt intake produced a similar distribution pattern of renin-expressing cells as
      did low salt intake. Conversely, increasing blood pressure by administration of
      the NOS inhibitor N-nitro-l-arginine methyl ester or of the adrenergic agonist
      phenylephrine in AT(1a)-/- mice kept on low salt intake produced a similar
      distribution pattern of renin-producing cells as did normal salt intake alone.
      These findings suggest that changes in preglomerular blood pressure may be an
      important mediator of the influence of salt intake on the number and distribution
      of renin-producing cells in the kidney.

PMID- 22357915
TI  - Proteomic profiling of the effect of metabolic acidosis on the apical membrane of
      the proximal convoluted tubule.
AB  - The physiological response to the onset of metabolic acidosis requires pronounced
      changes in renal gene expression. Adaptations within the proximal convoluted
      tubule support the increased extraction of plasma glutamine and the increased
      synthesis and transport of glucose and of NH(4)(+) and HCO(3)(-) ions. Many of
      these adaptations involve proteins associated with the apical membrane. To
      quantify the temporal changes in these proteins, proteomic profiling was
      performed using brush-border membrane vesicles isolated from proximal convoluted
      tubules (BBMV(PCT)) that were purified from normal and acidotic rats. This
      preparation is essentially free of contaminating apical membranes from other
      renal cortical cells. The analysis identified 298 proteins, 26% of which
      contained one or more transmembrane domains. Spectral counts were used to assess
      changes in protein abundance. The onset of acidosis produced a twofold, but
      transient, increase in the Na(+)-dependent glucose transporter and a more
      gradual, but sustained, increase (3-fold) in the Na(+)-dependent lactate
      transporter. These changes were associated with the loss of glycolytic and
      gluconeogenic enzymes that are contained in the BBMV(PCT) isolated from normal
      rats. In addition, the levels of gamma-glutamyltranspeptidase increased twofold,
      while transporters that participate in the uptake of neutral amino acids,
      including glutamine, were decreased. These changes could facilitate the
      deamidation of glutamine within the tubular lumen. Finally, pronounced increases
      were also observed in the levels of DAB2 (3-fold) and myosin 9 (7-fold), proteins
      that may participate in endocytosis of apical membrane proteins. Western blot
      analysis and accurate mass and time analyses were used to validate the spectral
      counting.

PMID- 22357916
TI  - Effects of ibuprofen treatment on the developing preterm baboon kidney.
AB  - Preterm neonates are commonly exposed postnatally to pharmacological treatments
      for a patent ductus arteriosus. Exposure of the developing kidney to nephrotoxic
      medications may adversely impact renal development. This study aimed to determine
      the effect of early postnatal ibuprofen treatment, both alone and in combination
      with a nitric oxide synthase inhibitor (NOSi), on renal development and
      morphology. Baboon neonates were delivered prematurely at 125-day (125d)
      gestation (term = 185d) and were euthanized at birth or postnatal day 6. Neonates
      were divided into four groups: 125d gestational controls (n = 8), Untreated (n =
      8), Ibuprofen (n = 6), and ibuprofen (Ibu)+NOSi (n = 4). Animals in the Ibuprofen
      and Ibu+NOSi groups received five doses of ibuprofen, with the Ibuprofen+NOSi
      animals additionally administered a NOS inhibitor (N(G)-monomethyl-l-arginine).
      There was no difference among groups in body weight, kidney weight, or glomerular
      generation number. Nephrogenic zone width was significantly reduced in the
      Ibuprofen group (123.5 +/- 7.4 MUm) compared with the 125d gestational control
      (176.1 +/- 6.9 MUm) and Untreated animals (169.7 +/- 78.8 MUm). In the Ibu+NOSi
      group, nephrogenic zone width averaged 152.7 +/- 3.9 MUm, which was not
      significantly different from any other group. Morphologically abnormal glomeruli
      were present at a range of 0.0-22.9% in the Untreated group, 0.0-6.1% in the
      Ibuprofen group, and 0.0-1.4% in the Ibu+NOSi group. In conclusion, early
      postnatal ibuprofen exposure is associated with a reduced nephrogenic zone width,
      which may suggest the early cessation of nephrogenesis following treatment.
      Ultimately, this may impact the number of nephrons formed in the preterm kidney.

PMID- 22357917
TI  - Reversal of renal dysfunction by targeted administration of VEGF into the
      stenotic kidney: a novel potential therapeutic approach.
AB  - Renal microvascular (MV) damage and loss contribute to the progression of renal
      injury in renovascular disease (RVD). Whether a targeted intervention in renal
      microcirculation could reverse renal damage is unknown. We hypothesized that
      intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal
      dysfunction and decrease renal injury in experimental RVD. Unilateral renal
      artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six
      weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were
      quantified in vivo in the stenotic kidney using multidetector computed tomography
      (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the
      stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo
      studies were repeated, and then renal MV density was quantified by 3D micro-CT,
      and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV
      density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2,
      Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS
      compared with normal controls. Remarkably, administration of VEGF at 6 wk
      normalized RBF (from 393.6 +/- 50.3 to 607.0 +/- 45.33 ml/min, P < 0.05 vs. RAS)
      and GFR (from 43.4 +/- 3.4 to 66.6 +/- 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk,
      accompanied by increased angiogenic signaling, augmented renal MV density, and
      attenuated renal scarring. This study shows promising therapeutic effects of a
      targeted renal intervention, using an established clinically relevant large
      animal model of chronic RAS. It also implies that disruption of renal MV
      integrity and function plays a pivotal role in the progression of renal injury in
      the stenotic kidney. Furthermore, it shows a high level of plasticity of renal
      microvessels to a single-dose VEGF-targeted intervention after established renal
      injury, supporting promising renoprotective effects of a novel potential
      therapeutic intervention to treat chronic RVD.

PMID- 22357918
TI  - Effects of insulin on Na and K transporters in the rat CCD.
AB  - We tested the effects of insulin (2 nM, 30-60 min) on principal cells of isolated
      split-open rat cortical collecting ducts (CCD) using whole-cell current
      measurements. Insulin addition to the superfusate of the tubules enhanced Na pump
      (ouabain-sensitive) current from 18 +/- 3 to 31 +/- 3 pA/cell in control and from
      74 +/- 9 to 126 +/- 11 pA/cell in high K-fed animals. It also more than doubled
      ROMK (tertiapin-Q-sensitive) K(+) currents in control CCD from 320 +/- 40 to 700
      +/- 80 pA/cell, although it did not affect this current in tubules from K-loaded
      rats. Insulin did not induce the appearance of amiloride-sensitive Na(+) current
      in control animals, while in high K-fed animals the currents were similar in the
      presence (140 +/- 30) and the absence (180 +/- 70 pA/cell) of insulin.
      Intraperitoneal injection of insulin plus hypertonic dextrose decreased Na
      excretion, as previously reported. However, injection of dextrose alone, or the
      nonmetabolized sugar mannose, had similar effects, suggesting that they were
      largely the result of vascular volume depletion rather than specific actions of
      the hormone. In summary, we find no evidence for acute upregulation of the
      epithelial Na channel (ENaC) by physiological concentrations of insulin in the
      mammalian CCD. However, the hormone does activate both the Na/K pump and apical
      K(+) channels and could, under some conditions, enhance renal K(+) secretion.

PMID- 22357919
TI  - The hormone melatonin stimulates renoprotective effects of "early outgrowth"
      endothelial progenitor cells in acute ischemic kidney injury.
AB  - Endothelial progenitor cells (EPCs) protect the kidney from acute ischemic
      injury. The aim of this study was to analyze whether pretreatment of murine
      "early outgrowth" EPCs (eEPCs) with the hormone melatonin increases the cells'
      renoprotective effects in the setting of murine acute ischemic renal failure.
      Male (8-12 wk old) C57Bl/6N mice were subjected to unilateral ischemia
      reperfusion injury postuninephrectomy (40 min). Postischemic animals were
      injected with either 0.5*10(6) untreated syngeneic murine eEPCs or with cells,
      pretreated with melatonin for 1 h. Injections were performed shortly after
      reperfusion of the kidney. While animals injected with untreated cells developed
      acute renal failure, eEPC pretreatment with melatonin dramatically improved
      renoprotective actions of the cells. These effects were completely reversed after
      cell pretreatment with melatonin and the MT-1/-2 antagonist luzindole. In vitro
      analysis revealed that melatonin reduced the amount of tumor growth factor-beta
      induced eEPC apoptosis/necrosis. Secretion of vascular endothelial growth factor
      by the cells was markedly stimulated by the hormone. In addition, migratory
      activity of eEPCs was enhanced by melatonin and supernatant from melatonin
      treated eEPCs stimulated migration of cultured mature endothelial cells. In
      summary, melatonin was identified as a new agonist of eEPCs in acute ischemic
      kidney injury.

PMID- 22357920
TI  - Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1
      production.
AB  - Collecting duct (CD) endothelin-1 (ET-1) is an important autocrine inhibitor of
      Na and water transport. CD ET-1 production is stimulated by extracellular fluid
      volume expansion and tubule fluid flow, suggesting a mechanism coupling CD Na
      delivery and ET-1 synthesis. A mouse cortical CD cell line, mpkCCDc14, was
      subjected to static or flow conditions for 2 h at 2 dyn/cm(2), followed by
      determination of ET-1 mRNA content. Flow with 300 mosmol/l NaCl increased ET-1
      mRNA to 65% above that observed under static conditions. Increasing perfusate
      osmolarity to 450 mosmol/l with NaCl or Na acetate increased ET-1 mRNA to ~184%
      compared with no flow, which was not observed when osmolarity was increased using
      mannitol or urea. Reducing Na concentration to 150 mosmol/l while maintaining
      total osmolarity at 300 mosmol/l with urea or mannitol decreased the flow
      response. Inhibition of epithelial Na channel (ENaC) with amiloride or benzamil
      abolished the flow response, suggesting involvement of ENaC in flow-regulated ET
      1 synthesis. Aldosterone almost doubled the flow response. Since Ca(2+) enhances
      CD ET-1 production, the involvement of plasma membrane and mitochondrial
      Na/Ca(2+) exchangers (NCX) was assessed. SEA0400 and KB-R7943, plasma membrane
      NCX inhibitors, did not affect the flow response. However, CGP37157, a
      mitochondrial NCX inhibitor, abolished the response. In summary, the current
      study indicates that increased Na delivery, leading to ENaC-mediated Na entry and
      mitochondrial NCX activity, is involved in flow-stimulated CD ET-1 synthesis.
      This constitutes the first report of either ENaC or mitochondrial NCX regulation
      of an autocrine factor in any biologic system.

PMID- 22357921
TI  - The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin
      production in mesangial cells.
AB  - Angiotensin II (ANG II) produced as result of activation of the renin-angiotensin
      system (RAS) plays a critical role in the pathogenesis of chronic kidney disease
      via its hemodynamic effects on the renal microcirculation as well as by its
      nonhemodynamic actions including the production of extracellular matrix proteins
      such as fibronectin, a multifunctional extracellular matrix protein that plays a
      major role in cell adhesion and migration as well as in the development of
      glomerulosclerosis. ETS-1 is an important transcription factor essential for
      normal kidney development and glomerular integrity. We previously showed that ANG
      II increases ETS-1 expression and is required for fibronectin production in
      mesangial cells. In these studies, we determined that ANG II induces
      phosphorylation of ETS-1 via activation of the type 1 ANG II receptor and that
      Erk1/2 and Akt/PKB phosphorylation are required for these effects. In addition,
      we characterized the role of ETS-1 on the transcriptional activation of
      fibronectin production in mesangial cells. We determined that ETS-1 directly
      activates the fibronectin promoter and by utilizing gel shift assays and
      chromatin immunoprecipitation assays identified two different ETS-1 binding sites
      that promote the transcriptional activation of fibronectin in response to ANG II.
      In addition, we identified the essential role of CREB and its coactivator p300 on
      the transcriptional activation of fibronectin by ETS-1. These studies unveil
      novel mechanisms involved in RAS-induced production of the extracellular matrix
      protein fibronectin in mesangial cells and establish the role of the
      transcription factor ETS-1 as a direct mediator of these effects.

PMID- 22357922
TI  - Modulation of spontaneous activity in the overactive bladder: the role of P2Y
      agonists.
AB  - Spinal cord transection (SCT) leads to an increase in spontaneous contractile
      activity in the isolated bladder that is reminiscent of an overactive bladder
      syndrome in patients with similar damage to the central nervous system. An
      increase in interstitial cell number in the suburothelial space between the
      urothelium and detrusor smooth muscle layer occurs in SCT bladders, and these
      cells elicit excitatory responses to purines and pyrimidines such as ATP, ADP,
      and UTP. We have investigated the hypothesis that these agents underlie the
      increase in spontaneous activity. Rats underwent lower thoracic spinal cord
      transection, and their bladder sheets or strips, with intact mucosa except where
      specified, were used for experiments. Isometric tension was recorded and
      propagating Ca(2+) and membrane potential (E(m)) waves were recorded by
      fluorescence imaging using photodiode arrays. SCT bladders were associated with
      regular spontaneous contractions (2.9 +/- 0.4/min); ADP, UTP, and UDP augmented
      the amplitude but not their frequency. With strips from such bladders, a P2Y(6)
      selective agonist (PSB0474) exerted similar effects. Fluorescence imaging of
      bladder sheets showed that ADP or UTP increased the conduction velocity of
      Ca(2+)/E(m) waves that were confined to regions of the bladder wall with an
      intact mucosa. When transverse bladder sections were used, Ca(2+)/E(m) waves
      originated in the suburothelial space and propagated to the detrusor and
      urothelium. Analysis of wave propagation showed that the suburothelial space
      exhibited properties of an electrical syncitium. These experiments are consistent
      with the hypothesis that P2Y-receptor agonists increase spontaneous contractile
      activity by augmenting functional activity of the cellular syncitium in the
      suburothelial space.

PMID- 22357923
TI  - Angiotensin AT1 receptor-associated protein Arap1 in the kidney vasculature is
      suppressed by angiotensin II.
AB  - Arap1 is a protein that interacts with angiotensin II type 1 (AT(1)) receptors
      and facilitates increased AT(1) receptor surface expression in vitro. In the
      present study, we assessed the tissue localization and regulation of Arap1 in
      vivo. Arap1 was found in various mouse organs, with the highest expression in the
      heart, kidney, aorta, and adrenal gland. Renal Arap1 protein was restricted to
      the vasculature and to glomerular mesangial cells and was absent from tubular
      epithelia. A similar localization was found in human kidneys. To test the
      hypothesis that angiotensin II may control renal Arap1 expression, mice were
      subjected to various conditions to alter the activity of the renin-angiotensin
      system. A high-salt diet (4% NaCl, 7 days) upregulated Arap1 expression in mice
      by 47% compared with controls (0.6% NaCl, P = 0.03). Renal artery stenosis (7
      days) or water restriction (48 h) suppressed Arap1 levels compared with controls
      (-64 and -62% in the clipped and contralateral kidney, respectively; and -50%
      after water restriction, P < 0.01). Angiotensin II infusion (2 MUg.kg(-1).min(
      1), 7 days) reduced Arap1 mRNA levels compared with vehicle by 29% (P < 0.01),
      whereas AT(1) antagonism (losartan, 30 mg.kg(-1).day(-1), 7 days) enhanced Arap1
      mRNA expression by 52% (P < 0.01); changes in mRNA were paralleled by Arap1
      protein abundance. Experiments with hydralazine and epithelial nitric oxide
      synthase-/- mice further suggested that Arap1 expression changed in parallel with
      angiotensin II, rather than with blood pressure per se. Similar to in vivo, Arap1
      mRNA and protein were suppressed by angiotensin II in a time- and dose-dependent
      manner in cultured mesangial cells. In summary, Arap1 is highly expressed in the
      renal vasculature, and its expression is suppressed by angiotensin II. Thus Arap1
      may serve as a local modulator of vascular AT(1) receptor function in vivo.

PMID- 22357924
TI  - A role for endothelial cells in promoting the maturation of astrocytes through
      the apelin/APJ system in mice.
AB  - Interactions between astrocytes and endothelial cells (ECs) are crucial for
      retinal vascular formation. Astrocytes induce migration and proliferation of ECs
      via their production of vascular endothelial growth factor (VEGF) and,
      conversely, ECs induce maturation of astrocytes possibly by the secretion of
      leukemia inhibitory factor (LIF). Together with the maturation of astrocytes,
      this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production
      in ECs are unclear. Here we show that apelin, a ligand for the endothelial
      receptor APJ, induces maturation of astrocytes mediated by the production of LIF
      from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis;
      however, aberrant overgrowth of endothelial networks with immature astrocyte
      overgrowth was induced. When ECs were stimulated with apelin, LIF expression was
      upregulated and intraocular injection of LIF into APJ-deficient mice suppressed
      EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in
      the maturation process of retinal angiogenesis.

PMID- 22357926
TI  - bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate
      Notch-induced overproliferation.
AB  - Drosophila larval neurogenesis is an excellent system for studying the balance
      between self-renewal and differentiation of a somatic stem cell (neuroblast).
      Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate
      precursors called GMCs or INPs. We show that E(spl)mgamma, E(spl)mbeta, E(spl)m8
      and Deadpan (Dpn), members of the basic helix-loop-helix-Orange protein family,
      are expressed in NBs but not in differentiated cells. Double mutation for the
      E(spl) complex and dpn severely affects the ability of NBs to self-renew, causing
      premature termination of proliferation. Single mutations produce only minor
      defects, which points to functional redundancy between E(spl) proteins and Dpn.
      Expression of E(spl)mgamma and m8, but not of dpn, depends on Notch signalling
      from the GMC/INP daughter to the NB. When Notch is abnormally activated in NB
      progeny cells, overproliferation defects are seen. We show that this depends on
      the abnormal induction of E(spl) genes. In fact E(spl) overexpression can partly
      mimic Notch-induced overproliferation. Therefore, E(spl) and Dpn act together to
      maintain the NB in a self-renewing state, a process in which they are assisted by
      Notch, which sustains expression of the E(spl) subset.

PMID- 22357925
TI  - A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1
      function in spinal neural precursor survival and motor axon arborization.
AB  - In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1)
      leading to prenatal death of all affected fetuses. Although the molecular roles
      of Gle1 in nuclear mRNA export and translation have been documented, no animal
      models for this disease have been reported. To elucidate the function of Gle1 in
      vertebrate development, we used the zebrafish (Danio rerio) model system. gle1
      mRNA is maternally deposited and widely expressed. Altering Gle1 using an
      insertional mutant or antisense morpholinos results in multiple defects,
      including immobility, small eyes, diminished pharyngeal arches, curved body axis,
      edema, underdeveloped intestine and cell death in the central nervous system.
      These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion
      also results in reduction of motoneurons and aberrant arborization of motor
      axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural
      precursors, not of differentiated motoneurons. Mosaic analyses further indicate
      that Gle1 activity is required extrinsically in the environment for normal motor
      axon arborization. Importantly, the zebrafish phenotypes caused by Gle1
      deficiency are only rescued by expressing wild-type human GLE1 and not by the
      disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the
      first functional characterization of Gle1 in vertebrate development and reveal
      its essential role in actively dividing cells. We propose that defective GLE1
      function in human LCCS1 results in both neurogenic and non-neurogenic defects
      linked to the apoptosis of proliferative organ precursors.

PMID- 22357928
TI  - Specialisation within the DWARF14 protein family confers distinct responses to
      karrikins and strigolactones in Arabidopsis.
AB  - Karrikins are butenolides derived from burnt vegetation that stimulate seed
      germination and enhance seedling responses to light. Strigolactones are
      endogenous butenolide hormones that regulate shoot and root architecture, and
      stimulate the branching of arbuscular mycorrhizal fungi. Thus, karrikins and
      strigolactones are structurally similar but physiologically distinct plant growth
      regulators. In Arabidopsis thaliana, responses to both classes of butenolides
      require the F-box protein MAX2, but it remains unclear how discrete responses to
      karrikins and strigolactones are achieved. In rice, the DWARF14 protein is
      required for strigolactone-dependent inhibition of shoot branching. Here, we show
      that the Arabidopsis DWARF14 orthologue, AtD14, is also necessary for normal
      strigolactone responses in seedlings and adult plants. However, the AtD14
      paralogue KARRIKIN INSENSITIVE 2 (KAI2) is specifically required for responses to
      karrikins, and not to strigolactones. Phylogenetic analysis indicates that KAI2
      is ancestral and that AtD14 functional specialisation has evolved subsequently.
      Atd14 and kai2 mutants exhibit distinct subsets of max2 phenotypes, and
      expression patterns of AtD14 and KAI2 are consistent with the capacity to respond
      to either strigolactones or karrikins at different stages of plant development.
      We propose that AtD14 and KAI2 define a class of proteins that permit the
      separate regulation of karrikin and strigolactone signalling by MAX2. Our results
      support the existence of an endogenous, butenolide-based signalling mechanism
      that is distinct from the strigolactone pathway, providing a molecular basis for
      the adaptive response of plants to smoke.

PMID- 22357929
TI  - Vimentin regulates peripheral nerve myelination.
AB  - Myelination is a complex process that requires coordinated Schwann cell-axon
      interactions during development and regeneration. Positive and negative
      regulators of myelination have been recently described, and can belong either to
      Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann
      cell and neuron cytoskeleton, the expression of which is timely and spatially
      regulated during development and regeneration. We now report that vimentin
      negatively regulates myelination, as loss of vimentin results in peripheral nerve
      hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice
      and in vitro in a myelinating co-culture system. We also show that this is due to
      a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type
      III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice
      rescues hypermyelination. Finally, we demonstrate that vimentin acts
      synergistically with TACE, a negative regulator of NRG1 type III activity, as
      shown by hypermyelination of double Vim/Tace heterozygous mice. Our results
      reveal a novel role for the intermediate filament vimentin in myelination, and
      indicate vimentin as a regulator of NRG1 type III function.

PMID- 22357927
TI  - 2-O-sulfotransferase regulates Wnt signaling, cell adhesion and cell cycle during
      zebrafish epiboly.
AB  - O-sulfotransferases modify heparan sulfate proteoglycans (HSPGs) by catalyzing
      the transfer of a sulfate to a specific position on heparan sulfate
      glycosaminoglycan (GAG) chains. Although the roles of specific HSPG modifications
      have been described in cell culture and invertebrates, little is known about
      their functions or abilities to modulate specific cell signaling pathways in
      vertebrate development. Here, we report that 2-O-sulfotransferase (2-OST) is an
      essential component of canonical Wnt signaling in zebrafish development. 2-OST
      deficient embryos have reduced GAG chain sulfation and are refractory to
      exogenous Wnt8 overexpression. Embryos in which maternally encoded 2-OST is
      knocked down have normal activation of several zygotic mesoderm, endoderm and
      ectoderm patterning genes, but have decreased deep cell adhesion and fail to
      initiate epiboly, which can be rescued by re-expression of 2-OST protein. Reduced
      cell adhesion and altered cell cycle regulation in 2-OST-deficient embryos are
      associated with decreased beta-catenin and E-cadherin protein levels at cell
      junctions, and these defects can be rescued by reactivation of the intracellular
      Wnt pathway, utilizing stabilized beta-catenin or dominant-negative Gsk3, but not
      by overexpression of Wnt8 ligand. Together, these results indicate that 2-OST
      functions within the Wnt pathway, downstream of Wnt ligand signaling and upstream
      of Gsk3beta and beta-catenin intracellular localization and function.

PMID- 22357930
TI  - The conserved transcription factor Mef2 has multiple roles in adult Drosophila
      musculature formation.
AB  - Muscle is an established paradigm for analysing the cell differentiation programs
      that underpin the production of specialised tissues during development. These
      programs are controlled by key transcription factors, and a well-studied
      regulator of muscle gene expression is the conserved transcription factor Mef2.
      In vivo, Mef2 is essential for the development of the Drosophila larval
      musculature: Mef2-null embryos have no differentiated somatic muscle. By
      contrast, a similar phenotype has not been seen in analyses of the function of
      Mef2 genes in other examples of myogenesis. These include using conditional
      mutant mice, using morpholinos in zebrafish and using hypomorphic mutants in
      Drosophila adult development. However, we show here that Mef2 is absolutely
      required for a diverse range of Drosophila adult muscle types. These include the
      dorso-longitudinal muscles (DLMs), the largest flight muscles, which are produced
      by tissue remodelling. Furthermore, we demonstrate that Mef2 has temporally
      separable functions in this remodelling and in muscle maintenance. Drosophila
      adult muscles are multi-fibre and physiologically diverse, in common with
      vertebrate skeletal muscles, but in contrast to Drosophila larval muscles. These
      results therefore establish the importance of Mef2 in multiple roles in examples
      of myogenesis that have parallels in vertebrates and are distinct from that
      occurring in Drosophila embryogenesis.

PMID- 22357931
TI  - Evolution of self-organisation in Dictyostelia by adaptation of a non-selective
      phosphodiesterase and a matrix component for regulated cAMP degradation.
AB  - Dictyostelium discoideum amoebas coordinate aggregation and morphogenesis by
      secreting cyclic adenosine monophosphate (cAMP) pulses that propagate as waves
      through fields of cells and multicellular structures. To retrace how this
      mechanism for self-organisation evolved, we studied the origin of the cAMP
      phosphodiesterase PdsA and its inhibitor PdiA, which are essential for cAMP wave
      propagation. D. discoideum and other species that use cAMP to aggregate reside in
      group 4 of the four major groups of Dictyostelia. We found that groups 1-3
      express a non-specific, low affinity orthologue of PdsA, which gained cAMP
      selectivity and increased 200-fold in affinity in group 4. A low affinity group 3
      PdsA only partially restored aggregation of a D. discoideum pdsA-null mutant, but
      was more effective at restoring fruiting body morphogenesis. Deletion of a group
      2 PdsA gene resulted in disruption of fruiting body morphogenesis, but left
      aggregation unaffected. Together, these results show that groups 1-3 use a low
      affinity PdsA for morphogenesis that is neither suited nor required for
      aggregation. PdiA belongs to a family of matrix proteins that are present in all
      Dictyostelia and consist mainly of cysteine-rich repeats. However, in its current
      form with several extensively modified repeats, PdiA is only present in group 4.
      PdiA is essential for initiating spiral cAMP waves, which, by organising large
      territories, generate the large fruiting structures that characterise group 4. We
      conclude that efficient cAMP-mediated aggregation in group 4 evolved by
      recruitment and adaptation of a non-selective phosphodiesterase and a matrix
      component into a system for regulated cAMP degradation.

PMID- 22357932
TI  - Differential regulation of node formation, nodal ciliogenesis and cilia
      positioning by Noto and Foxj1.
AB  - The mouse transcription factor Noto is expressed in the node and controls node
      morphogenesis, formation of nodal cilia and left-right asymmetry. Noto acts
      upstream of Foxj1, which regulates ciliogenesis in other mouse tissues. However,
      the significance of Foxj1 for the formation of cilia in the mouse node is
      unclear; in non-amniote species Foxj1 is required for ciliogenesis in the
      structures equivalent to the node. Here, we analyzed nodes, nodal cilia and nodal
      flow in mouse embryos in which we replaced the Noto-coding sequence with that of
      Foxj1, or in embryos that were deficient for Foxj1. We show that Foxj1 expressed
      from the Noto locus is functional and restores the formation of structurally
      normal motile cilia in the absence of Noto. However, Foxj1 is not sufficient for
      the correct positioning of cilia on the cell surface within the plane of the
      nodal epithelium, and cannot restore normal node morphology. We also show that
      Foxj1 is essential for ciliogenesis upstream of Rfx3 in the node. Thus, the
      function of Foxj1 in vertebrate organs of asymmetry is conserved, and Noto
      regulates node morphogenesis and the posterior localization of cilia on node
      cells independently of Foxj1.

PMID- 22357933
TI  - miR-125 potentiates early neural specification of human embryonic stem cells.
AB  - The role of microRNAs (miRNAs) as coordinators of stem cell fate has emerged over
      the last decade. We have used human embryonic stem cells to identify miRNAs
      involved in neural lineage commitment induced by the inhibition of TGFbeta-like
      molecule-mediated pathways. Among several candidate miRNAs expressed in the fetal
      brain, the two isoforms of miR-125 alone were detected in a time window
      compatible with a role in neural commitment in vitro. Functional analysis
      indicated that miR-125 isoforms were actively involved in the promotion of
      pluripotent cell conversion into SOX1-positive neural precursors. miR-125
      promotes neural conversion by avoiding the persistence of non-differentiated stem
      cells and repressing alternative fate choices. This was associated with the
      regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage
      commitment. Activation of miR-125 was directly responsive to the levels of
      TGFbeta-like molecules, placing miR-125 at the core of mechanisms that lead to
      the irreversible neural lineage commitment of pluripotent stem cells in response
      to external stimuli.

PMID- 22357934
TI  - Early evidence for complex social structure in Proboscidea from a late Miocene
      trackway site in the United Arab Emirates.
AB  - Many living vertebrates exhibit complex social structures, evidence for the
      antiquity of which is limited to rare and exceptional fossil finds. Living
      elephants possess a characteristic social structure that is sex-segregated and
      multi-tiered, centred around a matriarchal family and solitary or loosely
      associated groups of adult males. Although the fossil record of Proboscidea is
      extensive, the origin and evolution of social structure in this clade is
      virtually unknown. Here, we present imagery and analyses of an extensive late
      Miocene fossil trackway site from the United Arab Emirates. The site of Mleisa 1
      preserves exceptionally long trackways of a herd of at least 13 individuals of
      varying size transected by that of a single large individual, indicating the
      presence of both herding and solitary social modes. Trackway stride lengths and
      resulting body mass estimates indicate that the solitary individual was also the
      largest and therefore most likely a male. Sexual determination for the herd is
      equivocal, but the body size profile and number of individuals are commensurate
      with those of a modern elephant family unit. The Mleisa 1 trackways provide
      direct evidence for the antiquity of characteristic and complex social structure
      in Proboscidea.

PMID- 22357935
TI  - It is optimal to be optimistic about survival.
AB  - We investigate the optimal behaviour of an organism that is unable to obtain a
      reliable estimate of its mortality risk. In this case, natural selection will
      shape behaviour to be approximately optimal given the probability distribution of
      mortality risks in possible environments that the organism and its ancestors
      encountered. The mean of this distribution is the average mortality risk
      experienced by a randomly selected member of the species. We show that if an
      organism does not know the exact mortality risk, it should act as if the risk is
      less than the mean risk. This can be viewed as being optimistic. We argue that
      this effect is likely to be general.

PMID- 22357936
TI  - Mind the gap: genetic distance increases with habitat gap size in Florida scrub
      jays.
AB  - Habitat gap size has been negatively linked to movement probability in several
      species occupying fragmented landscapes. How these effects on movement behaviour
      in turn affect the genetic structure of fragmented populations at local scales is
      less well known. We tested, and confirmed, the hypothesis that genetic
      differentiation among adjacent populations of Florida scrub jays--an endangered
      bird species with poor dispersal abilities and a high degree of habitat
      specialization--increases with the width of habitat gaps separating them. This
      relationship was not an artefact of simple isolation-by-distance, as genetic
      distance was not correlated with the Euclidean distance between geographical
      centroids of the adjacent populations. Our results suggest that gap size affects
      movement behaviour even at remarkably local spatial scales, producing direct
      consequences on the genetic structure of fragmented populations. This finding
      shows that conserving genetic continuity for specialist species within fragmented
      habitat requires maintenance or restoration of preserve networks in which habitat
      gaps do not exceed a species-specific threshold distance.

PMID- 22357937
TI  - King penguin population on Macquarie Island recovers ancient DNA diversity after
      heavy exploitation in historic times.
AB  - Historically, king penguin populations on Macquarie Island have suffered greatly
      from human exploitation. Two large colonies on the island were drastically
      reduced to a single small colony as a result of harvesting for the blubber oil
      industry. However, recent conservation efforts have resulted in the king penguin
      population expanding in numbers and range to recolonize previous as well as new
      sites. Ancient DNA methods were used to estimate past genetic diversity and
      combined with studies of modern populations, we are now able to compare past
      levels of variation with extant populations on northern Macquarie Island. The
      ancient and modern populations are closely related and show a similar level of
      genetic diversity. These results suggest that the king penguin population has
      recovered past genetic diversity in just 80 years owing to conservation efforts,
      despite having seen the brink of extinction.

PMID- 22357938
TI  - On the centrality and uniqueness of species from the network perspective.
AB  - Identifying important species for maintaining ecosystem functions is a challenge
      in ecology. Since species are components of food webs, one way to conceptualize
      and quantify species importance is from a network perspective. The importance of
      a species can be quantified by measuring the centrality of its position in a food
      web, because a central node may have greater influence on others in the network.
      A species may also be important because it has a unique network position, such
      that its loss cannot be easily compensated. Therefore, for a food web to be
      robust, we hypothesize that central species must be functionally redundant in
      terms of their network position. In this paper, we test our hypothesis by
      analysing the Prince William Sound ecosystem. We found that species centrality
      and uniqueness are negatively correlated, and such an observation is also carried
      over to other food webs.

PMID- 22357939
TI  - Ambient noise increases missed detections in nestling birds.
AB  - Ambient noise can mask acoustic cues, making their detection and discrimination
      difficult for receivers. This can result in two types of error: missed
      detections, when receivers fail to respond to the appropriate cues, and false
      alarms, when they respond to inappropriate cues. Nestling birds are error-prone,
      sometimes failing to beg when parents arrive with food (committing missed
      detections) or begging in response to stimuli other than a parent's arrival
      (committing false alarms). Here, we ask whether the frequency of these errors by
      nestling tree swallows (Tachycineta bicolor) increases in the presence of noise.
      We found that nestlings exposed to noise had more missed detections than their
      unexposed counterparts. We also found that false alarms remained low overall and
      did not differ significantly between noise and quiet treatments. Our results
      suggest that nestlings living in noisy environments may be less responsive to
      their parents than nestlings in quieter environments.

PMID- 22357940
TI  - Cryptic sociality in rattlesnakes (Crotalus horridus) detected by kinship
      analysis.
AB  - Research on social behaviour has largely concentrated on birds and mammals in
      visually active, cooperatively breeding groups (although such systems are
      relatively rare) and focused much less on species that rarely interact other than
      for mating and parental care. We used microsatellite markers to characterize
      relatedness among aggregations of timber rattlesnakes (Crotalus horridus), a
      putatively solitary reptile that relies heavily on chemical cues, and found that
      juveniles and pregnant females preferentially aggregate with kin under certain
      conditions. The ability to recognize kin and enhance indirect fitness thus might
      be far more widespread than implied by studies of animals whose behaviour is
      primarily visually and/or acoustically mediated, and we predict that molecular
      markers will reveal many additional examples of 'cryptic' sociality.

PMID- 22357941
TI  - Hummingbirds have a greatly enlarged hippocampal formation.
AB  - Both field and laboratory studies demonstrate that hummingbirds (Apodiformes,
      Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal
      information that hummingbirds must retain and use daily is probably subserved by
      the hippocampal formation (HF), and therefore, hummingbirds should have a greatly
      expanded HF. Here, we compare the relative size of the HF in several hummingbird
      species with that of other birds. Our analyses reveal that the HF in hummingbirds
      is significantly larger, relative to telencephalic volume, than any bird examined
      to date. When expressed as a percentage of telencephalic volume, the hummingbird
      HF is two to five times larger than that of caching and non-caching songbirds,
      seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies
      their ability to remember the location, distribution and nectar content of
      flowers, but more detailed analyses are required to determine the extent to which
      this arises from an expansion of HF or a decrease in size of other brain regions.

PMID- 22357942
TI  - Mucolipin controls lysosome exocytosis in Dictyostelium.
AB  - Mucolipidosis type IV is a poorly understood lysosomal storage disease caused by
      alterations in the mucolipin lysosomal Ca(2+) channel. In this study, we
      generated mucolipin-knockout Dictyostelium cells, and observed that lysosome
      exocytosis was markedly increased in these cells compared with wild-type cells.
      In addition, mucolipin-knockout cells were more resistant to Ca(2+) deprivation,
      and the Ca(2+) concentration in their secretory lysosomes was decreased,
      suggesting that mucolipin transfers Ca(2+) ions from the cytosol to the lumen of
      secretory lysosomes. We speculate that mucolipin attenuates the fusogenic effect
      of local cytosolic increases in Ca(2+) by dissipating them into the lumen of
      lysosomal compartments.

PMID- 22357944
TI  - RECQL4 is essential for the transport of p53 to mitochondria in normal human
      cells in the absence of exogenous stress.
AB  - Mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome (RTS).
      A subset of RTS patients is predisposed to cancer and is sensitive to DNA
      damaging agents. The enhanced sensitivity of cells from RTS patients correlates
      with the accumulation of transcriptionally active nuclear p53. We found that in
      untreated normal human cells these two nuclear proteins, p53 and RECQL4, instead
      colocalize in the mitochondrial nucleoids. RECQL4 accumulates in mitochondria in
      all phases of the cell cycle except S phase and physically interacts with p53
      only in the absence of DNA damage. p53-RECQL4 binding leads to the masking of the
      nuclear localization signal of p53. The N-terminal 84 amino acids of RECQL4
      contain a mitochondrial localization signal, which causes the localization of
      RECQL4-p53 complex to the mitochondria. RECQL4-p53 interaction is disrupted after
      stress, allowing p53 translocation to the nucleus. In untreated normal cells
      RECQL4 optimizes de novo replication of mtDNA, which is consequently decreased in
      fibroblasts from RTS patients. Wild-type RECQL4-complemented RTS cells show
      relocalization of both RECQL4 and p53 to the mitochondria, loss of p53
      activation, restoration of de novo mtDNA replication and resistance to different
      types of DNA damage. In cells expressing Delta84 RECQL4, which cannot translocate
      to mitochondria, all the above functions are compromised. The recruitment of p53
      to the sites of de novo mtDNA replication is also regulated by RECQL4. Thus these
      findings elucidate the mechanism by which p53 is regulated by RECQL4 in
      unstressed normal cells and also delineates the mitochondrial functions of the
      helicase.

PMID- 22357943
TI  - Acute depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate impairs
      specific steps in endocytosis of the G-protein-coupled receptor.
AB  - Receptor endocytosis plays an important role in regulating the responsiveness of
      cells to specific ligands. Phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P(2)] has been shown to be crucial for endocytosis of some cell
      surface receptors, such as EGF and transferrin receptors, but its role in G
      protein-coupled receptor internalization has not been investigated. By using
      luciferase-labeled type 1 angiotensin II (AT1R), type 2C serotonin (5HT2CR) or
      beta(2) adrenergic (beta2AR) receptors and fluorescently tagged proteins (beta
      arrestin-2, plasma-membrane-targeted Venus, Rab5) we were able to follow the
      sequence of molecular interactions along the endocytic route of the receptors in
      HEK293 cells using the highly sensitive method of bioluminescence resonance
      energy transfer and confocal microscopy. To study the role of plasma membrane
      PtdIns(4,5)P(2) in receptor endocytosis, we used our previously developed
      rapamycin-inducible heterodimerization system, in which the recruitment of a 5
      phosphatase domain to the plasma membrane degrades PtdIns(4,5)P(2). Here we show
      that ligand-induced interaction of AT1, 5HT2C and beta(2)A receptors with beta
      arrestin-2 was unaffected by PtdIns(4,5)P(2) depletion. However, trafficking of
      the receptors to Rab5-positive early endosomes was completely abolished in the
      absence of PtdIns(4,5)P(2). Remarkably, removal of the receptors from the plasma
      membrane was reduced but not eliminated after PtdIns(4,5)P(2) depletion. Under
      these conditions, stimulated AT1 receptors clustered along the plasma membrane,
      but did not enter the cells. Our data suggest that in the absence of
      PtdIns(4,5)P(2), these receptors move into clathrin-coated membrane structures,
      but these are not cleaved efficiently and hence cannot reach the early endosomal
      compartment.

PMID- 22357945
TI  - Sub-diffraction imaging on standard microscopes through photobleaching microscopy
      with non-linear processing.
AB  - Visualization of organelles and molecules at nanometer resolution is
      revolutionizing the biological sciences. However, such technology is still
      limited for many cell biologists. We present here a novel approach using
      photobleaching microscopy with non-linear processing (PiMP) for sub-diffraction
      imaging. Bleaching of fluorophores both within the single-molecule regime and
      beyond allows visualization of stochastic representations of sub-populations of
      fluorophores by imaging the same region over time. Our method is based on
      enhancing the probable positions of the fluorophores underlying the images. The
      random nature of the bleached fluorophores is assessed by calculating the
      deviation of the local actual bleached fluorescence intensity to the average
      bleach expectation as given by the overall decay of intensity. Subtracting
      measured from estimated decay images yields differential images. Non-linear
      enhancement of maxima in these diffraction-limited differential images
      approximates the positions of the underlying structure. Summing many such
      processed differential images yields a super-resolution PiMP image. PiMP allows
      multi-color, three-dimensional sub-diffraction imaging of cells and tissues using
      common fluorophores and can be implemented on standard wide-field or confocal
      systems.

PMID- 22357946
TI  - VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and
      migration.
AB  - Planar cell polarity (PCP) describes the polarized orientation of cells within
      the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP
      signaling in migrating cells remain undefined. Here, the establishment of PCP
      must be coordinated with dynamic changes in cell adhesion and extracellular
      matrix (ECM) organization. During gastrulation, the membrane type-1 matrix
      metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and
      extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2)
      regulates the endocytosis and cell-surface availability of MMP14 in manner that
      is dependent on focal adhesion kinase. We demonstrate that zebrafish
      trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased
      ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of
      function convergence and extension phenotype. This study identifies a mechanism
      linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in
      migrating gastrula cells requires regulated proteolytic degradation or remodeling
      of the ECM. Our findings implicate matrix metalloproteinases as downstream
      effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2
      affects diverse morphogenetic processes.

PMID- 22357947
TI  - Molecular interactions of the physiological anti-hypertensive peptide catestatin
      with the neuronal nicotinic acetylcholine receptor.
AB  - Catestatin (CST), a chromogranin-A-derived peptide, is a potent endogenous
      inhibitor of the neuronal nicotinic acetylcholine receptor (nAChR). It exerts an
      anti-hypertensive effect by acting as a 'physiological brake' on transmitter
      release into the circulation. However, the mechanism of interaction of CST with
      nAChR is only partially understood. To unravel molecular interactions of the wild
      type human CST (CST-WT) as well as its naturally occurring variants (CST-364S and
      CST-370L, which have Gly->Ser and Pro->Leu substitutions, respectively) with the
      human alpha3beta4 nAChR, we generated a homology-modeled human alpha3beta4 nAChR
      structure and solution structures of CST peptides. Docking and molecular dynamics
      simulations showed that ~90% of interacting residues were within 15 N-terminal
      residues of CST peptides. The rank order of binding affinity of these peptides
      with nAChR was: CST-370L>CST-WT>CST-364S; the extent of occlusion of the receptor
      pore by these peptides was also in the same order. In corroboration with
      computational predictions, circular dichroism analysis revealed significant
      differences in global structures of CST peptides (e.g. the order of alpha-helical
      content was: CST-370L>CST-WT>CST-364S). Consistently, CST peptides blocked
      various stages of nAChR signal transduction, such as nicotine- or acetylcholine
      evoked inward current, rise in intracellular Ca(2+) and catecholamine secretion
      in or from neuron-differentiated PC12 cells, in the same rank order. Taken
      together, this study shows molecular interactions between human CST peptides and
      human alpha3beta4 nAChR, and demonstrates that alterations in the CST secondary
      structure lead to the gain of potency for CST-370L and loss of potency for CST
      364S. These findings have implications for understanding the nicotinic
      cholinergic signaling in humans.

PMID- 22357949
TI  - The fusion of early endosomes induces molecular-motor-driven tubule formation and
      fission.
AB  - Organelles in the endocytic pathway interact and communicate through the crucial
      mechanisms of fusion and fission. However, any specific link between fusion and
      fission has not yet been determined. To study the endosomal interactions with
      high spatial and temporal resolution, we enlarged the endosomes by two
      mechanistically different methods: by expression of the MHC-class-II-associated
      chaperone invariant chain (Ii; or CD74) or Rab5, both of which increased the
      fusion rate of early endosomes and resulted in enlarged endosomes. Fast homotypic
      fusions were studied, and immediately after the fusion a highly active and
      specific tubule formation and fission was observed. These explosive tubule
      formations following fusion seemed to be a direct effect of fusion. The tubule
      formations were dependent on microtubule interactions, and specifically
      controlled by Kif16b and dynein. Our results show that fusion of endosomes is a
      rapid process that destabilizes the membrane and instantly induces molecular
      motor-driven tubule formation and fission.

PMID- 22357948
TI  - Disruption of Kif3a in osteoblasts results in defective bone formation and
      osteopenia.
AB  - We investigated whether Kif3a in osteoblasts has a direct role in regulating
      postnatal bone formation. We conditionally deleted Kif3a in osteoblasts by
      crossing osteocalcin (Oc; also known as Bglap)-Cre with Kif3a(flox/null) mice.
      Conditional Kif3a-null mice (Kif3a(Oc-cKO)) had a 75% reduction in Kif3a
      transcripts in bone and osteoblasts. Conditional deletion of Kif3a resulted in
      the reduction of primary cilia number by 51% and length by 27% in osteoblasts.
      Kif3a(Oc-cKO) mice developed osteopenia by 6 weeks of age unlike Kif3a(flox/+)
      control mice, as evidenced by reductions in femoral bone mineral density (22%),
      trabecular bone volume (42%) and cortical thickness (17%). By contrast, Oc
      Cre;Kif3a(flox/+) and Kif3a(flox/null) heterozygous mice exhibited no skeletal
      abnormalities. Loss of bone mass in Kif3a(Oc-cKO) mice was associated with
      impaired osteoblast function in vivo, as reflected by a 54% reduction in mineral
      apposition rate and decreased expression of Runx2, osterix (also known as Sp7
      transcription factor 7; Sp7), osteocalcin and Dmp1 compared with controls.
      Immortalized osteoblasts from Kif3a(Oc-cKO) mice exhibited increased cell
      proliferation, impaired osteoblastic differentiation, and enhanced adipogenesis
      in vitro. Osteoblasts derived from Kif3a(Oc-cKO) mice also had lower basal
      cytosolic calcium levels and impaired intracellular calcium responses to fluid
      flow shear stress. Sonic hedgehog-mediated Gli2 expression and Wnt3a-mediated
      beta-catenin and Axin2 expression were also attenuated in Kif3a(Oc-cKO) bone and
      osteoblast cultures. These data indicate that selective deletion of Kif3a in
      osteoblasts disrupts primary cilia formation and/or function and impairs
      osteoblast-mediated bone formation through multiple pathways including
      intracellular calcium, hedgehog and Wnt signaling.

PMID- 22357950
TI  - Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially
      regulates receptor signalling and trafficking.
AB  - Serotonin receptors 5-HT(1A) and 5-HT(7) are highly coexpressed in brain regions
      implicated in depression. However, their functional interaction has not been
      established. In the present study we show that 5-HT(1A) and 5-HT(7) receptors
      form heterodimers both in vitro and in vivo. Foerster resonance energy transfer
      based assays revealed that, in addition to heterodimers, homodimers composed
      either of 5-HT(1A) or 5-HT(7) receptors together with monomers coexist in cells.
      The highest affinity for complex formation was obtained for the 5-HT(7)-5-HT(7)
      homodimers, followed by the 5-HT(7)-5-HT(1A) heterodimers and 5-HT(1A)-5-HT(1A)
      homodimers. Functionally, heterodimerization decreases 5-HT(1A)-receptor-mediated
      activation of G(i) protein without affecting 5-HT(7)-receptor-mediated
      signalling. Moreover, heterodimerization markedly decreases the ability of the 5
      HT(1A) receptor to activate G-protein-gated inwardly rectifying potassium
      channels in a heterologous system. The inhibitory effect on such channels was
      also preserved in hippocampal neurons, demonstrating a physiological relevance of
      heteromerization in vivo. In addition, heterodimerization is crucially involved
      in initiation of the serotonin-mediated 5-HT(1A) receptor internalization and
      also enhances the ability of the 5-HT(1A) receptor to activate the mitogen
      activated protein kinases. Finally, we found that production of 5-HT(7) receptors
      in the hippocampus continuously decreases during postnatal development,
      indicating that the relative concentration of 5-HT(1A)-5-HT(7) heterodimers and,
      consequently, their functional importance undergoes pronounced developmental
      changes.

PMID- 22357951
TI  - Kinesin-3 and dynein mediate microtubule-dependent co-transport of mRNPs and
      endosomes.
AB  - Long-distance transport of mRNAs is important in determining polarity in
      eukaryotes. Molecular motors shuttle large ribonucleoprotein complexes (mRNPs)
      containing RNA-binding proteins and associated factors along microtubules.
      However, precise mechanisms including the interplay of molecular motors and a
      potential connection to membrane trafficking remain elusive. Here, we solve the
      motor composition of transported mRNPs containing the RNA-binding protein Rrm4 of
      the pathogen Ustilago maydis. The underlying transport process determines the
      axis of polarity in infectious filaments. Plus-end-directed Kin3, a kinesin-3
      type motor, mediates anterograde transport of mRNPs and is also present in
      transport units moving retrogradely. Split dynein Dyn1-Dyn2 functions in
      retrograde movement of mRNPs. Plus-end-directed conventional kinesin Kin1 is
      indirectly involved by transporting minus-end-directed dynein back to plus ends.
      Importantly, we additionally demonstrate that Rrm4-containing mRNPs colocalise
      with the t-SNARE Yup1 on shuttling endosomes and that functional endosomes are
      essential for mRNP movement. Either loss of Kin3 or removal of its lipid-binding
      pleckstrin-homology domain abolishes Rrm4-dependent movement without preventing
      colocalisation of Rrm4 and Yup1-positive endosomes. In summary, we uncovered the
      combination of motors required for mRNP shuttling along microtubules.
      Furthermore, intimately linked co-transport of endosomes and mRNPs suggests
      vesicle hitchhiking as mode of mRNP transport.

PMID- 22357952
TI  - Association of translation factor eEF1A with defective ribosomal products
      generates a signal for aggresome formation.
AB  - Aggresome formation is initiated upon proteasome failure, and facilitates
      autophagic clearance of protein aggregates to protect cells from proteotoxicity.
      Here we demonstrate that proteasome inhibition generates a signaling event to
      trigger aggresome formation. In aggresome signaling, the cell senses a build-up
      of aberrant newly synthesized proteins. The translation elongation factor eEF1A
      associated with these species, and knockdown of this factor suppressed aggresome
      formation. We used the Legionella toxin SidI to distinguish between the function
      of eEF1A in translation and its novel function in the aggresome formation. In
      fact, although it strongly inhibited translation, this toxin had only a marginal
      effect on aggresome formation. Furthermore, SidI reduced the threshold of the
      aberrant ribosomal products for triggering aggresome formation. Therefore, eEF1A
      binds defective polypeptides released from ribosomes, which generates a signal
      that triggers aggresome formation.

PMID- 22357954
TI  - SNAREs, HOPS and regulatory lipids control the dynamics of vacuolar actin during
      homotypic fusion in S. cerevisiae.
AB  - Homotypic vacuole fusion requires SNAREs, the Rab Ypt7p, the tethering complex
      HOPS, regulatory lipids and actin. In Saccharomyces cerevisiae, actin functions
      at two stages of vacuole fusion. Pre-existing actin filaments are depolymerized
      to allow docking and assembly of the vertex ring (a microdomain enriched in
      proteins and lipids that mediate fusion). Actin is then polymerized late in the
      pathway to aid fusion. Here, we report that the fusion machinery regulates the
      accumulation of actin at the vertex ring. Using Cy3-labeled yeast actin to track
      its dynamics, we found that its vertex enrichment was abolished when actin
      monomers were stabilized by latrunculin-B, independent of the extent of
      incorporation. By contrast, stabilization of filamentous actin with
      jasplakinolide markedly augmented actin vertex enrichment. Importantly, agents
      that inhibit SNAREs, Ypt7p and HOPS inhibited the vertex enrichment of actin,
      demonstrating that the cytoskeleton and the fusion machinery are interdependently
      regulated. Actin mobilization was also inhibited by ligating ergosterol and
      PtdIns(3)P, whereas the ligation or modification of PtdIns(4,5)P(2) augmented the
      vertex enrichment of actin. The proteins and lipids that regulated actin
      mobilization to the vertex did not affect the total incorporation of Cy3-actin,
      indicating that actin mobilization and polymerization activities can be
      dissociated during membrane fusion.

PMID- 22357953
TI  - Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of
      G3BP2.
AB  - Wnt signaling is initiated upon binding of Wnt proteins to Frizzled proteins and
      their co-receptors LRP5 and 6. The signal is then propagated to several
      downstream effectors, mediated by the phosphoprotein scaffold, dishevelled. We
      report a novel role for arginine methylation in regulating Wnt3a-stimulated LRP6
      phosphorylation. G3BP2, a dishevelled-associated protein, is methylated in
      response to Wnt3a. The Wnt3a-induced LRP6 phosphorylation is attenuated by G3BP2
      knockdown, chemical inhibition of methyl transferase activity or expression of
      methylation-deficient mutants of G3BP2. Arginine methylation of G3BP2 appears to
      be a Wnt3a-sensitive 'switch' regulating LRP6 phosphorylation and canonical Wnt
      beta-catenin signaling.

PMID- 22357955
TI  - Ligand oligomerization state controls Tie2 receptor trafficking and angiopoietin
      2-specific responses.
AB  - Angiopoietin 1 (Ang1) is an activating ligand for the endothelial receptor
      tyrosine kinase Tie2, whereas Ang2 acts as a context-dependent agonist or
      antagonist that has a destabilizing effect on the vasculature. The molecular
      mechanisms responsible for the versatile functions of Ang2 are poorly understood.
      We show here that Ang2, but not Ang1, induces Tie2 translocation to the specific
      cell-matrix contact sites located at the distal end of focal adhesions. The Ang2
      specific Tie2 translocation was associated with distinct Tie2 activation and
      downstream signals which differed from those of Ang1, and led to impaired cell
      motility and weak cell-matrix adhesion. We demonstrate that the different
      oligomeric or multimeric forms of the angiopoietins induce distinct patterns of
      Tie2 trafficking; the lower oligomerization state of native Ang2 was crucial for
      the Ang2-specific Tie2 redistribution, whereas multimeric structures of Ang1 and
      Ang2 induced similar responses. The Ang2-specific Tie2 trafficking to cell-matrix
      contacts was also dependent on the cell substratum, alpha2beta1-integrin
      containing cell-matrix adhesion sites and intact microtubules. Our data indicate
      that the different subcellular trafficking of Tie2-Ang2 and Tie2-Ang1 complexes
      generates ligand-specific responses in the angiopoietin-Tie signaling pathway,
      including modulation of cell-matrix interactions.

PMID- 22357956
TI  - Reprogramming cell shape with laser nano-patterning.
AB  - Cell shape in vitro can be directed by geometrically defined micropatterned
      adhesion substrates. However conventional methods are limited by the fixed
      micropattern design, which cannot recapitulate the dynamic changes of the cell
      microenvironment. Here, we manipulate the shape of living cells in real time by
      using a tightly focused pulsed laser to introduce additional geometrically
      defined adhesion sites. The sub-micrometer resolution of the laser patterning
      allowed us to identify the critical distances between cell adhesion sites
      required for cell shape extension and contraction. This easy-to-handle method
      allows the precise control of specific actin-based structures that regulate cell
      architecture. Actin filament bundles or branched meshworks were induced,
      displaced or removed in response to specific dynamic modifications of the cell
      adhesion pattern. Isotropic branched actin meshworks could be forced to assemble
      new stress fibers locally and polarised in response to specific geometrical cues.

PMID- 22357957
TI  - Loss of Porcupine impairs convergent extension during gastrulation in zebrafish.
AB  - Porcupine (Porcn), an O-acyltransferase located in the endoplasmic reticulum
      (ER), is required for lipidation of Wnt proteins to enable their trafficking from
      the ER in mammalian cell culture. However, it is unclear whether Porcn is
      required for trafficking of all members of the Wnt family. In this study, we
      investigated the function of Porcn in zebrafish embryos. We identified two
      zebrafish homologs of porcupine, porcn and porcupine-like (porcn-l). Zebrafish
      porcn, but not porcn-l, restores secretion of Wnt proteins in porcn-deficient
      mouse L cells. Morpholino-mediated knockdown of porcn in zebrafish embryos
      impairs convergence and extension (CE) during gastrulation without changing
      embryonic patterning. Moreover, porcn interacts genetically with wnt5b and wnt11
      in regulating CE. By contrast, porcn-deficient embryos do not exhibit phenotypes
      caused by failure in canonical Wnt signaling, which is activated by several Wnt
      ligands, including Wnt3a. Furthermore, expression of genes regulated by the
      canonical Wnt signaling pathway is not perturbed in knockdown embryos relative to
      that in controls. Although the trafficking and lipidation of ectopically
      expressed zebrafish Wnt5b and mouse Wnt5a are impaired in porcn-deficient
      embryos, those of ectopically expressed Wnt3a are less or not affected. In
      addition, the secretion of Wnt5a is inhibited by less Porcn inhibitor than that
      of Wnt3a in HEK293T cells. Thus, a decrease of Porcn activity does not
      equivalently affect trafficking and lipidation of different Wnt proteins in
      zebrafish embryos and in cultured mammalian cells.

PMID- 22357958
TI  - Chronic photo-oxidative stress and subsequent MCP-1 activation as causative
      factors for age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness among
      the elderly in developed countries. Although pathogenic factors, such as
      oxidative stress, inflammation and genetics are thought to contribute to the
      development of AMD, little is known about the relationships and priorities
      between these factors. Here, we show that chronic photo-oxidative stress is an
      environmental factor involved in AMD pathogenesis. We first demonstrated that
      exposure to light induced phospholipid oxidation in the mouse retina, which was
      more prominent in aged animals. The induced oxidized phospholipids led to an
      increase in the expression of monocyte chemoattractant protein-1, which then
      resulted in macrophage accumulation, an inflammatory process. Antioxidant
      treatment prevented light-induced phospholipid oxidation and the subsequent
      increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine
      2; CCL2), which are the beginnings of the light-induced changes. Subretinal
      application of oxidized phospholipids induced choroidal neovascularization, a
      characteristic feature of wet-type AMD, which was inhibited by blocking monocyte
      chemoattractant protein-1. These findings strongly suggest that a sequential
      cascade from photic stress to inflammatory processes through phospholipid
      oxidation has an important role in AMD pathogenesis. Finally, we succeeded in
      mimicking human AMD in mice with low-level, long-term photic stress, in which
      characteristic pathological changes, including choroidal neovascularization
      formation, were observed. Therefore, we propose a consecutive pathogenic pathway
      involving photic stress, oxidation of phospholipids and chronic inflammation,
      leading to angiogenesis. These findings add to the current understanding of AMD
      pathology and suggest protection from oxidative stress or suppression of the
      subsequent inflammation as new potential therapeutic targets for AMD.

PMID- 22357959
TI  - Candesartan cilexetil improves angiotensin II type 2 receptor-mediated neurite
      outgrowth via the PI3K-Akt pathway in fructose-induced insulin-resistant rats.
AB  - We have shown previously that stimulation of the angiotensin II type 2 receptor
      (AT(2)R) results in nerve facilitation. In this study, we determined the capacity
      of candesartan to correct expression patterns characteristic of neuropathy and
      AT(2)R-mediated neurite outgrowth in the fructose-induced insulin-resistant rat,
      which is one of the human hyperinsulinemia models. Wistar rats received a 15%
      (w/v) fructose solution in their drinking water for 4 weeks (fructose-drinking
      rats [FDRs]), with or without candesartan (5 mg/kg/day). We evaluated
      physiological and behavioral parameters and performed immunohistochemical
      studies. We found that the FDR developed insulin resistance and downregulated
      both AT(2)R neuronal function and phosphorylated Akt expression in dorsal root
      ganglia (DRG) neurons. Candesartan improved neurite outgrowth in the FDR, which
      was associated with the restoration of AT(2)R and phosphorylated Akt expression.
      Furthermore, downregulation of phosphoinositide 3-kinase (PI3K) inhibited AT(2)R
      mediated neurite outgrowth in control DRG cells. PI3K activation increased AT(2)R
      mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells.
      These results suggest that the decrease of AT(2)R-mediated neurite outgrowth in
      FDRs is likely to be the result of decreased PI3K-dependent Akt activation.
      Candesartan improved AT(2)R neuronal function and Akt phosphorylation, which were
      associated with sensory nerve defects and insulin sensitivity in the FDR.

PMID- 22357960
TI  - Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant
      diabetes.
AB  - Recently, missense mutations upstream of preproinsulin's signal peptide (SP)
      cleavage site were reported to cause mutant INS gene-induced diabetes of youth
      (MIDY). Our objective was to understand the molecular pathogenesis using
      metabolic labeling and assays of proinsulin export and insulin and C-peptide
      production to examine the earliest events of insulin biosynthesis, highlighting
      molecular mechanisms underlying beta-cell failure plus a novel strategy that
      might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S
      is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin
      A(SP24)D is inefficiently cleaved at an improper site, producing two
      subpopulations of molecules. Both show impaired oxidative folding and are
      retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER
      exit of coexpressed wild-type proinsulin, accounting for its dominant-negative
      behavior. Upon increased expression of ER-oxidoreductin-1, preproinsulin-A(SP24)D
      remains blocked but oxidative folding of wild-type proinsulin improves,
      accelerating its ER export and increasing wild-type insulin production. We
      conclude that the efficiency of SP cleavage is linked to the oxidation of
      (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of
      the mutant as well as that of coexpressed wild-type proinsulin. Improving
      oxidative folding of wild-type proinsulin may provide a feasible way to rescue
      insulin production in patients with MIDY.

PMID- 22357961
TI  - Glucagon-like peptide 1 recruits microvasculature and increases glucose use in
      muscle via a nitric oxide-dependent mechanism.
AB  - Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes
      vasodilation independent of insulin. We examined the effect of GLP-1 on muscle
      microvasculature and glucose uptake. After confirming that GLP-1 potently
      stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells,
      overnight-fasted adult male rats received continuous GLP-1 infusion (30
      pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood
      volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood
      flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min
      and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely
      increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral
      blood flow. This effect persisted throughout the 120-min infusion period, leading
      to a greater than twofold increase in muscle MBF (P < 0.02). These changes were
      paralleled with increases in plasma NO levels, muscle interstitial oxygen
      saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS
      inhibition blocked GLP-1-mediated increases in muscle MBV, glucose disposal, NO
      production, and muscle insulin clearance/uptake. In conclusion, GLP-1 acutely
      recruits microvasculature and increases basal glucose uptake in muscle via a NO
      dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin
      action by expanding microvascular endothelial surface area.

PMID- 22357962
TI  - Effect of the PTPN22 and INS risk genotypes on the progression to clinical type 1
      diabetes after the initiation of beta-cell autoimmunity.
AB  - We set out to analyze the role of two major non-HLA gene polymorphisms associated
      with type 1 diabetes (T1D), PTPN22 1858C/T and insulin gene INS-23 A/T in
      progression to clinical T1D after the appearance of beta-cell autoimmunity. The
      study population comprised 249 children with HLA-associated T1D susceptibility.
      All subjects were persistently positive for at least one of the T1D-associated
      biochemically defined autoantibodies (insulin autoantibody, GAD antibody, or IA-2
      antibody), and 136 subjects presented with T1D over a median follow-up of 4.3
      years (range 0.0-12.5) after the appearance of the first autoantibody. The PTPN22
      1858T allele was strongly associated with progression to T1D after the appearance
      of the first biochemically defined beta-cell autoantibody (hazard ratio 1.68 [95%
      CI 1.09-2.60], P = 0.02 Cox regression analysis, multivariate test), and the
      effect remained similar when analyzed after the appearance of the second
      autoantibody (P = 0.013), whereas INS-23 HphI AA genotype was not associated with
      progression to clinical diabetes after the appearance of the first or second
      autoantibody (P = 0.38 and P = 0.88, respectively). The effect of the INS risk
      genotype seems to be limited to the induction and early phases of beta-cell
      autoimmunity, but the PTPN22 1858T allele instead affects the initiation and late
      progression phase of diabetes-associated autoimmunity.

PMID- 22357963
TI  - Cholecystokinin plays a novel protective role in diabetic kidney through anti
      inflammatory actions on macrophage: anti-inflammatory effect of cholecystokinin.
AB  - Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In
      this article, we show that cholecystokinin (CCK) is expressed in the kidney and
      exerts renoprotective effects through its anti-inflammatory actions. DNA
      microarray showed that CCK was upregulated in the kidney of diabetic wild-type
      (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We
      induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R(-/
      ),-2R(-/-)) mice, and furthermore, we performed a bone marrow transplantation
      study using CCK-1R(-/-) mice to determine the role of CCK-1R on macrophages in
      the diabetic kidney. Diabetic CCK-1R(-/-),-2R(-/-) mice revealed enhanced
      albuminuria and inflammation in the kidney compared with diabetic WT mice. In
      addition, diabetic WT mice with CCK-1R(-/-) bone marrow-derived cells developed
      more albuminuria than diabetic CCK-1R(-/-) mice with WT bone marrow-derived
      cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S)
      ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and
      infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S
      inhibited both expression of tumor necrosis factor-alpha and chemotaxis in
      cultured THP-1 cells. These results suggest that CCK suppresses the activation of
      macrophage and expression of proinflammatory genes in diabetic kidney. Our
      findings may provide a novel strategy of therapy for the early stage of diabetic
      nephropathy.

PMID- 22357964
TI  - Salicylate downregulates 11beta-HSD1 expression in adipose tissue in obese mice
      and in humans, mediating insulin sensitization.
AB  - Recent trials show salicylates improve glycemic control in type 2 diabetes, but
      the mechanism is poorly understood. Expression of the glucocorticoid-generating
      enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue
      is increased in vitro by proinflammatory cytokines and upregulated in obesity.
      11beta-HSD1 inhibition enhances insulin sensitivity. We hypothesized that
      salicylates downregulate 11beta-HSD1 expression, contributing to their metabolic
      efficacy. We treated diet-induced obese (DIO) 11beta-HSD1-deficient mice and
      C57Bl/6 mice with sodium salicylate for 4 weeks. Glucose tolerance was assessed
      in vivo. Tissue transcript levels were assessed by quantitative PCR and enzyme
      activity by incubation with (3)H-steroid. Two weeks' administration of salsalate
      was also investigated in a randomized double-blind placebo-controlled crossover
      study in 16 men, with measurement of liver 11beta-HSD1 activity in vivo and
      adipose tissue 11beta-HSD1 transcript levels ex vivo. In C57Bl/6 DIO mice,
      salicylate improved glucose tolerance and downregulated 11beta-HSD1 mRNA and
      activity selectively in visceral adipose. DIO 11beta-HSD1-deficient mice were
      resistant to these metabolic effects of salicylate. In men, salsalate reduced
      11beta-HSD1 expression in subcutaneous adipose, and in vitro salicylate treatment
      reduced adipocyte 11beta-HSD1 expression and induced adiponectin expression only
      in the presence of 11beta-HSD1 substrate. Reduced intra-adipose glucocorticoid
      regeneration by 11beta-HSD1 is a novel mechanism that contributes to the
      metabolic efficacy of salicylates.

PMID- 22357966
TI  - Ubiquitin and SUMO in DNA repair at a glance.

PMID- 22357965
TI  - Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes
      nitric oxide production, lowers blood pressure, and protects against
      atherosclerosis.
AB  - Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1)
      are associated with insulin resistance, diabetes, and cardiovascular disease. We
      investigated whether increasing IGFBP1 levels can prevent the development of
      these disorders. Metabolic and vascular phenotype were examined in response to
      human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous
      for deletion of insulin receptors (IR(+/-)), and ApoE(-/-) mice. Direct effects
      of human (h)IGFBP1 on nitric oxide (NO) generation and cellular signaling were
      studied in isolated vessels and in human endothelial cells. IGFBP1 circulating
      levels were markedly suppressed in dietary-induced obese mice. Overexpression of
      hIGFBP1 in obese mice reduced blood pressure, improved insulin sensitivity, and
      increased insulin-stimulated NO generation. In nonobese IR(+/-) mice,
      overexpression of hIGFBP1 reduced blood pressure and improved insulin-stimulated
      NO generation. hIGFBP1 induced vasodilatation independently of IGF and increased
      endothelial NO synthase (eNOS) activity in arterial segments ex vivo, while in
      endothelial cells, hIGFBP1 increased eNOS Ser(1177) phosphorylation via
      phosphatidylinositol 3-kinase signaling. Finally, in ApoE(-/-) mice,
      overexpression of hIGFBP1 reduced atherosclerosis. These favorable effects of
      hIGFBP1 on insulin sensitivity, blood pressure, NO production, and
      atherosclerosis suggest that increasing IGFBP1 concentration may be a novel
      approach to prevent cardiovascular disease in the setting of insulin resistance
      and diabetes.

PMID- 22357968
TI  - The role of ubiquitylation in receptor endocytosis and endosomal sorting.
AB  - Ligand-induced activation of transmembrane receptors activates intracellular
      signaling cascades that control vital cellular processes, such as cell
      proliferation, differentiation, migration and survival. Receptor signaling is
      modulated by several mechanisms to ensure that the correct biological outcome is
      achieved. One such mechanism, which negatively regulates receptor signaling,
      involves the modification of receptors with ubiquitin. This post-translational
      modification can promote receptor endocytosis and targets receptors for lysosomal
      degradation, thereby ensuring termination of receptor signaling. In this
      Commentary, we review the roles of ubiquitylation in receptor endocytosis and
      degradative endosomal sorting by drawing on the epidermal growth factor receptor
      (EGFR) as a well-studied example. Furthermore, we elaborate on the molecular
      basis of ubiquitin recognition along the endocytic pathway through compartment
      specific ubiquitin-binding proteins and highlight how endocytic sorting
      machineries control these processes. In addition, we discuss the importance of
      ubiquitin-dependent receptor endocytosis for the maintenance of cellular
      homeostasis and in the prevention of diseases such as cancer.

PMID- 22357967
TI  - Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control.
AB  - The covalent modification of proteins with ubiquitin is required for accurate
      cell division in all eukaryotes. Ubiquitylation depends on an enzymatic cascade,
      in which E3 enzymes recruit specific substrates for modification. Among ~600
      human E3s, the SCF (Skp1-cullin1-F-box) and the APC/C (anaphase-promoting
      complex/cyclosome) are known for driving the degradation of cell cycle regulators
      to accomplish irreversible cell cycle transitions. The cell cycle machinery
      reciprocally regulates the SCF and APC/C through various mechanisms, including
      the modification of these E3s or the binding of specific inhibitors. Recent
      studies have provided new insight into the intricate relationship between
      ubiquitylation and the cell division apparatus as they revealed roles for
      atypical ubiquitin chains, new mechanisms of substrate and E3 regulation, as well
      as extensive crosstalk between ubiquitylation enzymes. Here, we review these
      emerging regulatory mechanisms of ubiquitin-dependent cell cycle control and
      discuss how their manipulation might provide therapeutic benefits in the future.

PMID- 22357969
TI  - Cellular functions of the DUBs.
AB  - Ubiquitylation is a reversible post-translational modification that has emerged
      as a key regulator of most complex cellular processes. It may rival
      phosphorylation in scope and exceed it in complexity. The dynamic nature of
      ubiquitylation events is important for governing protein stability, maintaining
      ubiquitin homeostasis and controlling ubiquitin-dependent signalling pathways.
      The human genome encodes ~80 active deubiquitylating enzymes (DUBs, also referred
      to as deubiquitinases), which exhibit distinct specificity profiles towards the
      various ubiquitin chain topologies. As a result of their ability to reverse
      ubiquitylation, these enzymes control a broad range of key cellular processes. In
      this Commentary we discuss the cellular functions of DUBs, such as their role in
      governing membrane traffic and protein quality control. We highlight two key
      signalling pathways--the Wnt and transforming growth factor beta (TGF-beta)
      pathways, for which dynamic ubiquitylation has emerged as a key regulator. We
      also discuss the roles of DUBs in the nucleus, where they govern transcriptional
      activity and DNA repair pathways.

PMID- 22357970
TI  - Induction of membrane circular dorsal ruffles requires co-signalling of integrin
      ILK-complex and EGF receptor.
AB  - Integrin and receptor tyrosine kinase signalling networks cooperate to regulate
      various biological functions. The molecular details underlying the integration of
      both signalling networks remain largely uncharacterized. Here we identify a
      signalling module composed of a fibronectin-alpha5beta1-integrin-integrin-linked
      kinase (ILK) complex that, in concert with epidermal growth factor (EGF) cues,
      cooperatively controls the formation of transient actin-based circular dorsal
      ruffles (DRs) in fibroblasts. DR formation depends on the precise spatial
      activation of Src at focal adhesions by integrin and EGF receptor signals, in an
      ILK-dependent manner. In a SILAC-based phosphoproteomics screen we identified the
      tumour-suppressor Cyld as being required for DR formation induced by alpha5beta1
      integrin and EGF receptor co-signalling. Furthermore, EGF-induced Cyld tyrosine
      phosphorylation is controlled by integrin-ILK and Src as a prerequisite for DR
      formation. This study provides evidence for a novel function of integrin-ILK and
      EGF signalling crosstalk in mediating Cyld tyrosine phosphorylation and fast
      actin-based cytoskeletal rearrangements.

PMID- 22357971
TI  - The ketone body beta-hydroxybutyric acid influences agouti-related peptide
      expression via AMP-activated protein kinase in hypothalamic GT1-7 cells.
AB  - beta-Hydroxybutyric acid (BHBA) acts in the brain to influence feeding behaviour,
      but the underlying molecular mechanisms are unclear. GT1-7 hypothalamic cells
      expressing orexigenic agouti-related peptide (AGRP) were used to study the AMP
      activated protein kinase (AMPK) pathway known to integrate dietary and hormonal
      signals for food intake regulation. In a 25 mM glucose culture medium, BHBA
      increased intracellular calcium concentrations and the expression of
      monocarboxylate transporter 1 (MCT1 (SLC16A1)). Phosphorylation of AMPK-alpha
      (PRKAA1 and PRKAA2) at Thr(172) was diminished after 2 h but increased after 4 h.
      Its downstream target, the mammalian target of rapamycin, was increasingly
      phosphorylated on Ser(2448) after 2 h but not changed after 4 h of BHBA
      treatment. After 4 h, BHBA treatment also increased Agrp mRNA expression. This
      increase was prevented by preincubation with the AMPK inhibitor Compound C. The
      inhibition of MCT1 activity by p-hydroxymercuribenzoate suppressed BHBA
      stimulated AMPK phosphorylation but did not prevent BHBA-induced Agrp mRNA
      expression. This finding demonstrates that BHBA triggers the AMPK pathway
      resulting in orexigenic signalling under 25 mM glucose culture conditions. Under
      conditions of 5.5 mM glucose, however, BHBA marginally increased intracellular
      calcium but significantly decreased AMPK phosphorylation and Agrp mRNA
      expression, demonstrating that under physiological conditions BHBA reduces
      central orexigenic signalling.

PMID- 22357972
TI  - Binding kinetics redefine the antagonist pharmacology of the corticotropin
      releasing factor type 1 receptor.
AB  - Corticotropin-releasing factor (CRF) receptor antagonists are under preclinical
      and clinical investigation for stress-related disorders. In this study the impact
      of receptor-ligand binding kinetics on CRF1 receptor antagonist pharmacology was
      investigated by measuring the association rate constant (k1), dissociation rate
      constant (k-1), and kinetically derived affinity at 37 degrees C. Three aspects
      of antagonist pharmacology were reevaluated: comparative binding activity of
      advanced compounds, in vivo efficacy, and structure-activity relationships.
      Twelve lead compounds, with little previously noted difference of affinity,
      varied substantially in their kinetic binding activity with a 510-fold range of
      kinetically derived affinity (k-1/k1), 170-fold range of k-1, and 13-fold range
      of k1. The k-1 values indicated previous affinity measurements were not close to
      equilibrium, resulting in compression of the measured affinity range.
      Dissociation was exceptionally slow for three ligands (k-1 t(1/2) of 1.6-7.2 h at
      37 degrees C). Differences of binding behavior were consistent with in vivo
      pharmacodynamics (suppression of adrenocorticotropin in adrenalectomized rats).
      Ligand concentration-effect relationships correlated with their kinetically
      derived affinity. Two ligands that dissociated slowly (53 and 130 min) produced
      prolonged suppression, whereas only transient suppression was observed with a
      more rapidly dissociating ligand (16 min). Investigating the structure-activity
      relationship indicated exceptionally low values of k1, approaching 100,000-fold
      less than the diffusion-limited rate. Retrospective interpretation of medicinal
      chemistry indicates optimizing specific elements of chemical structure overcame
      kinetic barriers in the association pathway, for example, constraint of the
      pendant aromatic orthogonal to the ligand core. Collectively, these findings
      demonstrate receptor binding kinetics provide new dimensions for understanding
      and potentially advancing the pharmacology of CRF1 receptor antagonists.

PMID- 22357973
TI  - sigma-1 Receptor agonist SKF10047 inhibits glutamate release in rat cerebral
      cortex nerve endings.
AB  - sigma-1 Receptors are expressed in the brain, and their activation has been shown
      to prevent neuronal death associated with glutamate toxicity. This study
      investigates the possible mechanism and effect of [2S-(2alpha,6alpha,11R*]
      1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol
      (SKF10047), a sigma-1 receptor agonist, on endogenous glutamate release in the
      nerve terminals of rat cerebral cortex. Results show that SKF10047 inhibited the
      release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP), and
      the sigma-1 receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2
      (dimethylamino)ethylamine (BD1047) blocked this phenomenon. The effects of
      SKF10047 on the evoked glutamate release were prevented by the chelating
      extracellular Ca2+ions and the vesicular transporter inhibitor bafilomycin A1.
      However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate
      did not have any effect on the action of SKF10047. SKF10047 decreased the
      depolarization-induced increase in the cytosolic free Ca2+ concentration
      ([Ca2+](C)), but did not alter 4-AP-mediated depolarization. Furthermore, the
      effects of SKF10047 on evoked glutamate release were prevented by blocking the
      Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking the
      ryanodine receptors or the mitochondrial Na+/Ca2+ exchange. In addition,
      conventional protein kinase C (PKC) inhibitors abolished the SKF10047 effect on 4
      AP-evoked glutamate release. Western blot analyses showed that SKF10047 decreased
      the 4-AP-induced phosphorylation of PKC and PKCalpha. These results show that
      sigma-1 receptor activation inhibits glutamate release from rat cortical nerve
      terminals. This effect is linked to a decrease in [Ca2+](C) caused by Ca2+ entry
      through presynaptic voltage-dependent Ca2+ channels and the suppression of the
      PKC signaling cascade.

PMID- 22357975
TI  - The NHS reforms war: politics by any other name.

PMID- 22357974
TI  - Charge and geometry of residues in the loop 2 beta hairpin differentially affect
      agonist and ethanol sensitivity in glycine receptors.
AB  - Recent studies highlighted the importance of loop 2 of alpha1 glycine receptors
      (GlyRs) in the propagation of ligand-binding energy to the channel gate.
      Mutations that changed polarity at position 52 in the beta hairpin of loop 2
      significantly affected sensitivity to ethanol. The present study extends the
      investigation to charged residues. We found that substituting alanine with the
      negative glutamate at position 52 (A52E) significantly left-shifted the glycine
      concentration response curve and increased sensitivity to ethanol, whereas the
      negative aspartate substitution (A52D) significantly right-shifted the glycine
      EC50 but did not affect ethanol sensitivity. It is noteworthy that the uncharged
      glutamine at position 52 (A52Q) caused only a small right shift of the glycine
      EC50 while increasing ethanol sensitivity as much as A52E. In contrast, the
      shorter uncharged asparagine (A52N) caused the greatest right shift of glycine
      EC50 and reduced ethanol sensitivity to half of wild type. Collectively, these
      findings suggest that charge interactions determined by the specific geometry of
      the amino acid at position 52 (e.g., the 1-A chain length difference between
      aspartate and glutamate) play differential roles in receptor sensitivity to
      agonist and ethanol. We interpret these results in terms of a new homology model
      of GlyR based on a prokaryotic ion channel and propose that these mutations form
      salt bridges to residues across the beta hairpin (A52E-R59 and A52N-D57). We
      hypothesize that these electrostatic interactions distort loop 2, thereby
      changing agonist activation and ethanol modulation. This knowledge will help to
      define the key physical-chemical parameters that cause the actions of ethanol in
      GlyRs.

PMID- 22357976
TI  - What Mr. Lansley could have learnt from the past.

PMID- 22357977
TI  - How should medical journals deal with errors?

PMID- 22357978
TI  - Broken Britain--prophecy or fantasy? Riots and labelling theory.

PMID- 22357979
TI  - Misplaced criticism of breast screening research.

PMID- 22357980
TI  - What can quality improvement learn from evidence-based medicine?

PMID- 22357981
TI  - Jacob Lockhart Clarke's and John Hughlings Jackson's first description of
      syringomyelia.

PMID- 22357982
TI  - Behaviour and control of influenza in institutions and small societies.
AB  - A literature review was undertaken to assess the impact of influenza in enclosed
      societies. The literature spanned 120 years and included both readily accessible
      material from online keyword searches, as well as more obscure paper documents
      found through in-depth library research. Enclosed societies have been
      predominantly found in some type of institution through this period although
      noticeable similarities exist in communities isolated by distance and geography.
      We observe that no matter how isolated a community is, it is not necessarily
      insulated from infection by influenza and that even where there are no
      complicating factors, such as the age distribution or the presence of individuals
      with greater susceptibility in the enclosed population, their organization tends
      to increase influenza transmission and the risk of secondary infection. The
      collected accounts demonstrate important features of outbreaks in such societies
      and the necessity of considering them in pandemic planning: in particular, rapid
      intervention is essential for the control of influenza spread in such
      circumstances. Recent experience has shown that administration of modern
      antiviral drugs, such as neuraminidase inhibitors are effective at moderating
      outbreaks of influenza, but only in combination with other methods of control. In
      more remote communities where such drugs are not, or less, readily available, and
      medical care is limited, such outbreaks can still pose particular difficulties.
      In all cases delay in correct diagnosis, detection of an outbreak or the
      implementation of control measures can result in the majority of the enclosed
      population succumbing to the disease.

PMID- 22357983
TI  - Daniel Sutton, a forgotten 18th century clinician scientist.

PMID- 22357984
TI  - The grass isn't always greener.

PMID- 22357988
TI  - Incidental myocardial infarct on conventional nongated CT: a review of the
      spectrum of findings with gated CT and cardiac MRI correlation.
AB  - OBJECTIVE: Myocardial infarctions (MIs) are frequently evident on routine chest
      or abdominal CT, even when studies are not performed for cardiac-specific
      indications. However, the telltale signs of an MI may be easily overlooked.
      Herein, we present the spectrum of appearances of MIs, including areas of fat
      attenuation, myocardial calcifications, focal areas of wall thinning or aneurysm
      formation, and perfusion abnormalities. Thrombi, especially when present at the
      apex of the left ventricle, may also suggest an MI. CONCLUSION: The increased use
      of CT in the evaluation of patients for a variety of indications gives the
      radiologist the unique opportunity to recognize findings consistent with MI in
      patients who may not have a prior diagnosis of ischemic heart disease.

PMID- 22357989
TI  - Coronary artery calcium can predict all-cause mortality and cardiovascular events
      on low-dose CT screening for lung cancer.
AB  - OBJECTIVE: Performing coronary artery calcium (CAC) screening as part of low-dose
      CT lung cancer screening has been proposed as an efficient strategy to detect
      people with high cardiovascular risk and improve outcomes of primary prevention.
      This study aims to investigate whether CAC measured on low-dose CT in a
      population of former and current heavy smokers is an independent predictor of all
      cause mortality and cardiac events. SUBJECTS AND METHODS: We used a case-cohort
      study and included 958 subjects 50 years old or older within the screen group of
      a randomized controlled lung cancer screening trial. We used Cox proportional
      hazard models to compute hazard ratios (HRs) adjusted for traditional
      cardiovascular risk factors to predict all-cause mortality and cardiovascular
      events. RESULTS: During a median follow-up of 21.5 months, 56 deaths and 127
      cardiovascular events occurred. Compared with a CAC score of 0, multivariate
      adjusted HRs for all-cause mortality for CAC scores of 1-100, 101-1000, and more
      than 1000 were 3.00 (95% CI, 0.61-14.93), 6.13 (95% CI, 1.35-27.77), and 10.93
      (95% CI, 2.36-50.60), respectively. Multivariate-adjusted HRs for coronary events
      were 1.38 (95% CI, 0.39-4.90), 3.04 (95% CI, 0.95-9.73), and 7.77 (95% CI, 2.44
      24.75), respectively. CONCLUSION: This study shows that CAC scoring as part of
      low-dose CT lung cancer screening can be used as an independent predictor of all
      cause mortality and cardiovascular events.

PMID- 22357990
TI  - Diagnostic performance of combined noninvasive anatomic and functional assessment
      with dual-source CT and adenosine-induced stress dual-energy CT for detection of
      significant coronary stenosis.
AB  - OBJECTIVE: The purpose of our study was to prospectively evaluate the incremental
      diagnostic value of combined dual-source coronary CT angiography (CTA) and CT
      myocardial perfusion imaging (MPI) for the detection of significant coronary
      stenoses. SUBJECTS AND METHODS: Forty-five patients with known coronary artery
      disease detected by dual-source coronary CTA were investigated by adenosine
      induced stress dual-source CTA and conventional coronary angiography. Analysis
      was performed in three steps: classification of coronary stenosis severity using
      dual-source coronary CTA, identification of myocardial perfusion defects using
      rest and stress CT MPI, and reclassification of coronary stenosis severity
      according to combined dual-source coronary CTA and CT MPI. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of dual-source coronary CTA before and after CT MPI were calculated on a per
      vessel basis compared with conventional coronary angiography as the standard of
      reference. RESULTS: Dual-source coronary CTA revealed 87 significantly stenotic
      vessels in 45 patients. Conventional coronary angiography revealed significant
      stenoses in 73 vessels in 42 patients. CT MPI showed myocardial perfusion defects
      in 81 vessel territories in 43 patients. After the CT MPI analysis, dual-source
      coronary CTA identified significant stenoses in 77 coronary vessels in 42
      patients. Sensitivity, specificity, PPV, and NPV of the dual-source coronary CTA
      on a per-vessel basis before CT MPI were 91.8%, 67.7%, 73.6%, and 87.5%,
      respectively, and after CT MPI were 93.2%, 85.5%, 88.3%, and 91.4%, respectively.
      The area under the receiver operating characteristic curve increased
      significantly from 0.798 to 0.893 (p = 0.004). CONCLUSION: Combined dual-source
      coronary CTA and CT MPI provides incremental diagnostic value compared with dual
      source coronary CTA alone for the detection of significant coronary stenoses.

PMID- 22357991
TI  - Adenosine-stress dynamic myocardial perfusion imaging with second-generation dual
      source CT: comparison with conventional catheter coronary angiography and SPECT
      nuclear myocardial perfusion imaging.
AB  - OBJECTIVE: The purpose of this article is to evaluate the feasibility of
      adenosine-stress dynamic myocardial perfusion imaging (MPI) with 128-MDCT dual
      source CT for detecting myocardial ischemia in comparison with conventional
      catheter coronary angiography and nuclear MPI. SUBJECTS AND METHODS: Thirty
      patients (21 men and nine women; mean [+/- SD] age, 59.2 +/- 7.6 years)
      prospectively underwent a combined stress CT perfusion and CT angiography (CTA)
      examination. Complete time-attenuation curves of the myocardium were acquired
      with prospectively ECG-triggered axial images at two alternating positions.
      Myocardial blood flow (MBF) was quantified according to dynamic CT perfusion, and
      MBF values of normal and abnormal segments were compared. Findings on CT
      perfusion were compared with those for stress and rest SPECT. Perfusion defects
      according to CT were correlated to flow-obstructing stenosis detected on CTA and
      catheter coronary angiography. RESULTS: On stress CT perfusion, 19 patients (63%)
      and 83 of 504 segments (16%) had perfusion abnormalities. There was a significant
      difference in MBF values between normal (142.9 +/- 30.6 mL/100 mL/min) and
      hypoperfused (90.0 +/- 22.8 mL/100 mL/min) segments (p < 0.001). With nuclear MPI
      results as a comparison, the sensitivity, specificity, positive predictive value,
      and negative predictive value of CT perfusion for identifying segments with
      perfusion defects were 0.85, 0.92, 0.55, and 0.98, respectively. On a per-vessel
      basis, sensitivity, specificity, positive predictive value, and negative
      predictive value for detecting flow-obstructing stenosis were, respectively,
      1.00, 0.757, 0.541, and 1.00 for CT perfusion; 0.90, 0.514, 0.346, and 0.947 for
      CTA; and 0.90, 0.814, 0.581, and 0.966 for CT perfusion combined with CTA.
      CONCLUSION: Adenosine-stress CT perfusion detects myocardial perfusion defects in
      good correlation with nuclear MPI. CT perfusion combined with CTA improves the
      diagnostic accuracy for identifying flow-obstructing stenosis compared with CTA
      alone.

PMID- 22357992
TI  - CT of coronary heart disease: Part 1, CT of myocardial infarction, ischemia, and
      viability.
AB  - OBJECTIVE: This article reviews the CT-based approaches aimed at the assessment
      of myocardial infarction, ischemia, and viability described in the recent
      literature. CONCLUSION: Rapid advances in CT technology not only have improved
      visualization of coronary arteries but also increasingly enable noncoronary
      myocardial applications, including analysis of wall motion and the state of the
      myocardial blood supply. These advancements hold promise for eventually
      accomplishing the goal of comprehensively evaluating coronary heart disease with
      a single noninvasive modality.

PMID- 22357993
TI  - CT of coronary heart disease: Part 2, Dual-phase MDCT evaluates late symptom
      recurrence in ST-segment elevation myocardial infarction patients after
      revascularization.
AB  - OBJECTIVE: The purpose of the study was to investigate dual-phase MDCT for
      assessing obstructive lesions and the extent and severity of the subtending
      myocardium at risk in patients presenting with chest pain syndromes 9 or more
      months after having undergone revascularization for the treatment of ST-segment
      elevation myocardial infarction (STEMI). MATERIALS AND METHODS: Dual-phase 64
      MDCT was performed on 135 patients with recurring chest symptoms 9 months or more
      after revascularization (mean +/- SD, 23 +/- 11 months after index invasive
      angiogram for treatment of STEMI). Obstructive lesions (>= 50% stenosis) were
      detected by MDCT angiography and the extent of myocardium at risk was detected by
      delayed phase 3D myocardium maps. A myocardium at-risk score based on MDCT
      findings was defined as the extent of myocardium at risk governed by the coronary
      lesion and weighted by lesion severity. Results were compared with stress
      redistribution (201)Tl-SPECT and invasive angiography. RESULTS: In restenotic,
      new, progressive, and previously obstructive lesions that are not currently
      progressive, analysis of assessable segments (1966/2025, 97.1%) obtained true
      positive detection rates of 88.1%, 88.6%, 82.9%, and 100%, respectively; false
      negative detection rates were 5.3%, 1.6%, 2.9%, and 8.8%. In 124 patients (91.9%)
      in whom all segments were assessable, the MDCT-based myocardium at-risk score
      correlated with the SPECT-based summed difference score (SDS) (r = 0.841, p <
      0.001). For detecting SPECT-based SDS >= 1 and SDS > 3, areas under the receiver
      operating characteristic curve for the MDCT-based myocardium at-risk score were
      0.874 (95% CI, 0.805-0.942) and 0.938 (95% CI, 0.895-0.981), with optimal cutoff
      values of 2.68 and 5.01, respectively. CONCLUSION: Dual-phase MDCT is useful in
      detecting different patterns of obstructive lesions and the extent of myocardium
      at risk as an alternative for therapeutic planning in patients presenting with
      late symptoms after treatment for acute myocardial infarction.

PMID- 22357994
TI  - Chest radiography in the ICU: Part 1, Evaluation of airway, enteric, and pleural
      tubes.
AB  - OBJECTIVE: In this pictorial essay, we discuss and illustrate normal and aberrant
      positioning of nonvascular support and monitoring devices frequently used in
      critically ill patients, including endotracheal and tracheostomy tubes, chest
      tubes, and nasogastric and nasoenteric tubes, as well as their inherent
      complications. CONCLUSION: The radiographic evaluation of the support and
      monitoring devices used in patients in the ICU is important because the
      potentially serious complications arising from their introduction and use are
      often not clinically apparent. Familiarity with normal and abnormal radiographic
      findings is critical for the detection of these complications.

PMID- 22357995
TI  - Chest radiography in the ICU: Part 2, Evaluation of cardiovascular lines and
      other devices.
AB  - OBJECTIVE: In this pictorial essay, we discuss and illustrate normal and aberrant
      positioning of the cardiovascular support and monitoring devices frequently used
      in critically ill patients, including central venous catheters, pulmonary artery
      catheters, left atrial catheters, transvenous pacemakers, automatic implantable
      cardioverter defibrillators, intraaortic counterpulsation balloon pump, and
      ventricular assist devices, as well as their inherent complications. CONCLUSION:
      The radiographic evaluation of the support and monitoring devices used in
      patients in the ICU is important, because the potentially serious complications
      arising from their introduction and use are often not clinically apparent.
      Familiarity with normal and abnormal radiographic findings is critical for the
      detection of these complications.

PMID- 22357996
TI  - MRI steatosis grading: development and initial validation of a color mapping
      system.
AB  - OBJECTIVE: The purpose of this article is to develop and validate a chemical
      shift imaging-derived color mapping system for evaluation of liver steatosis.
      MATERIALS AND METHODS: Opposed phase MRI was evaluated for 85 subjects (51 with
      presumed nonalcoholic fatty liver disease and 34 healthy volunteers). Liver
      signal intensity loss was compared with histologic analysis for 52 subjects,
      assuming grade 0 steatosis for healthy volunteers, to determine signal-intensity
      loss threshold points differentiating steatosis grades and subsequent Spearman
      correlation. Color scale grading was then applied for 78 subjects. Interpretation
      of color maps for steatosis severity and heterogeneity was performed by three
      readers. Analyses of agreement among readers and of color map steatosis grade
      with biopsy were performed using weighted kappa values. RESULTS: The numbers of
      subjects with steatosis grades 0, 1, 2, and 3 were 41, 12, 13, and 19,
      respectively. A correlation of 0.90 was obtained using selected threshold values
      of 5.9% or less, 6-26.1%, 26.2-36.8%, and greater than 36.8% for steatosis grades
      0, 1, 2, and 3, respectively. Interobserver agreement for color map grading of
      steatosis was excellent (kappa = 0.93-0.94). Color map interpretation for all
      readers also showed excellent agreement with histologic findings for whole liver
      (kappa = 0.82-0.86) and estimated biopsy site location (kappa = 0.81-0.86;
      anterior region of right lobe). Heterogeneous steatosis on color maps was
      identified in 56-60% of subjects with nonalcoholic fatty liver disease and in 7%
      of healthy volunteers and was associated with greater disagreement between color
      map and histology grading (61-74%) compared with the whole group (37-40%).
      CONCLUSION: MRI-derived color map estimation of liver steatosis grade appears to
      be reproducible and accurate.

PMID- 22357997
TI  - Is gadoxetate disodium-enhanced MRI useful for detecting local recurrence of
      hepatocellular carcinoma after radiofrequency ablation therapy?
AB  - OBJECTIVE: The purpose of our study was to determine whether gadoxetate disodium
      enhanced MRI improves the detection of locally recurrent hepatocellular carcinoma
      (HCC) after radiofrequency ablation therapy. MATERIALS AND METHODS: Forty-two
      consecutive patients (26 men and 16 women; mean age, 70.9 years) who had
      undergone radiofrequency ablation therapy for HCC were examined by gadoxetate
      disodium-enhanced MRI. Three independent radiologists reviewed two sets of MR
      images separately. Set 1 contained unenhanced T1-weighted, T2-weighted, and
      contrast-enhanced extracellular phase images, and set 2 contained unenhanced T1
      weighted, T2-weighted, and contrast-enhanced extracellular and hepatocyte phase
      images. Diagnostic accuracies were determined by receiver operating
      characteristic (ROC) curve analysis. RESULTS: Of the 61 ablated lesions included,
      10 developed local recurrence and 51 did not. Sensitivity (60-80% and 70-80% for
      sets 1 and 2, respectively), specificity (90-98% and 92-100%), and accuracy (87
      95% and 89-97%) were not improved by adding hepatocyte phase images. Rather, mean
      area under the ROC curve (AUC) significantly decreased from 0.94 for set 1 to
      0.82 for set 2 (p = 0.046), and the AUC of the radiologist with the least
      experience significantly decreased from 0.91 to 0.75 (p = 0.037). CONCLUSION: For
      gadoxetate disodium-enhanced MRI, the detection of local recurrence of HCC after
      radiofrequency ablation therapy was not found to be improved by including
      hepatocyte phase images. Furthermore, detection may be further impaired when a
      less-experienced radiologist interprets the images.

PMID- 22357998
TI  - Diffusion-weighted MRI for locally recurrent prostate cancer after external beam
      radiotherapy.
AB  - OBJECTIVE: The objectives of our study were to establish the apparent diffusion
      coefficients (ADCs) of tumor and nontumor irradiated tissues in patients with
      suspected postradiation recurrence of prostate cancer and to determine the
      sensitivity and specificity of a combination of T2-weighted and diffusion
      weighted imaging (DWI) for detecting local recurrence. MATERIALS AND METHODS:
      Twenty-four patients with rising prostate-specific antigen levels after having
      completed radiation therapy 30-130 months earlier (median, 62 months) underwent
      endorectal T2-weighted imaging and DWI (b = 0, 100, 300, 500, and 800 s/mm(2))
      followed by transrectal ultrasound (TRUS)-guided biopsy. Images were scored
      prospectively as positive for tumor if a region of low signal intensity on T2
      weighted imaging within the prostate corresponded with a focally restricted area
      on the ADC map. A region of interest (ROI) was drawn around the suspicious lesion
      on a single slice of the ADC map and a corresponding ROI was drawn around
      presumed nontumor irradiated peripheral zone and central gland tissues on the
      opposite side of the prostate. The sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) were determined against TRUS
      guided biopsy reference standard (octant, n = 17; sextant, n = 5; two samples, n
      = 1; 12 samples, n = 1). RESULTS: Sixteen of 24 patients (66.7%) had positive
      histology findings. The median tumor ROI area was 0.37 cm(2) (quartiles, 0.30 and
      0.82 cm(2)). The sensitivity, specificity, PPV, and NPV for detecting tumor were
      93.8%, 75%, 88.2%, and 85.7%, respectively. A cutoff ADC of 1216 * 10(-6) mm(2)/s
      could predict tumor with 100% sensitivity and 96% specificity (area under the
      receiver operating characteristic curve = 0.992). CONCLUSION: An ADC derived from
      DWI is a useful adjunct to T2-weighted MRI for detecting local tumor recurrence
      larger than 0.4 cm(2) within the prostate.

PMID- 22357999
TI  - CT-based determination of maximum ureteral stone area: a predictor of spontaneous
      passage.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that the maximum
      axial area of ureteral stones is a more accurate predictor of spontaneous passage
      than the maximum axial diameter. MATERIALS AND METHODS: This study
      retrospectively reviewed 211 consecutive emergency department patients (mean age,
      48.8 years; age range, 18-88 years) with acute flank pain due to ureteral stones
      diagnosed using unenhanced CT. Measurements of maximum atrial area were obtained
      using fixed (FTM) and variable (VTM) threshold methods. For the FTM, stones were
      segmented using an attenuation threshold of 130 HU. For the VTM, stones were
      segmented using an attenuation threshold determined by one half of individual
      stone attenuation. Measurements of maximum atrial diameter were obtained using
      soft-tissue and bone window settings. Receiver operating characteristic (ROC)
      analysis was used to compare the accuracy of maximum atrial area with maximum
      atrial diameter measurements for predicting spontaneous passage. RESULTS: Fifty
      seven patients (27%) required urologic intervention. The areas under the ROC
      curve (AUC) of maximum atrial area using FTM (0.83, p = 0.013) and VTM (0.84, p =
      0.004) were larger than the AUC (0.8, p = 0.4) for maximum atrial diameter using
      bone window settings or AUC (0.79) for maximum atrial iameter using soft-tissue
      window settings. For stones with maximum atrial diameter (in soft-tissue window
      settings) > 5 mm and <= 10 mm, the accuracy of maximum atrial area using VTM (AUC
      = 0.75) and FTM (AUC = 0.74) was superior to the accuracy of maximum atrial
      diameter in soft-tissue (AUC = 0.67) and bone (AUC = 0.69) window settings (p <
      0.05) in predicting spontaneous passage. CONCLUSION: Determination of the maximum
      axial area may improve the accuracy in predicting spontaneous passage of ureteral
      stones, particularly those between 5 and 10 mm.

PMID- 22358000
TI  - Diagnostic yield of CT urography in the evaluation of young adults with
      hematuria.
AB  - OBJECTIVE: CT urography is increasingly used as the initial imaging test in
      patients with hematuria. The aim of our study was to determine the yield of CT
      urography in young adults with hematuria to see whether single phase unenhanced
      CT would have been sufficient. MATERIALS AND METHODS: We reviewed medical records
      of consecutive patients undergoing CT urography between March 2000 and July 2009
      at our tertiary medical center. Of 5400 CT urograms performed, 375 (6.9%) in 359
      patients aged 40 years or younger with hematuria were included in the study.
      Urographic findings were tabulated according to their clinical significance. CT
      images were reviewed to see whether contrast-enhanced images were necessary for
      diagnosis. RESULTS: A clinically significant source was found in 83 of 375
      examinations (22.1%), including 42 of 142 (29.6%) for gross hematuria, 29 of 181
      (16.0%) for microscopic hematuria, and 12 of 52 (23.1%) for hematuria of
      unspecified subtype. The most common clinically significant findings were renal
      or ureteral calculi (n = 73 [75.3%]); four malignancies were also detected.
      Ninety-two (94.8%) of 97 clinically significant findings were evident on
      unenhanced images. All significant findings that required contrast-enhanced
      images for diagnosis occurred in patients with predisposing medical conditions.
      CONCLUSION: A clinically significant source of hematuria was detected in 22.1% of
      CT urograms of young adults. However, an unenhanced CT alone may be sufficient in
      patients without additional predisposing medical conditions, thereby reducing
      radiation dose in this radiosensitive population.

PMID- 22358001
TI  - Mandated radiologist-performed electronic order entry: effect on CT oral contrast
      administration.
AB  - OBJECTIVE: The purpose of this study was to determine whether radiologist
      performed electronic order entry affects use of oral contrast material for CT.
      Contrast media have been classified as medications by The Joint Commission, which
      necessitates a physician order for their administration. MATERIALS AND METHODS:
      In a retrospective study, rates of use of oral and IV contrast material for
      inpatient abdominopelvic CT examinations performed 6 months before and 6 months
      after the date of implementation of computerized physician order entry were
      calculated. Radiologist perception of order entry time was assessed by survey;
      order entry time was measured for 10 blinded radiologists. Descriptive, chi
      square, and Student t test statistics were used. RESULTS: A protocol that
      normally includes oral or IV contrast administration was used for 1693 CT
      examinations (784 before and 909 after May 25, 2010). No significant change (p >
      0.05) was found in ratios of indications for CT, rates of use of IV contrast
      material, or rates of use of oral contrast material after computerized physician
      order entry was implemented. The mean perceived order entry time was 3 minutes 3
      seconds (weighted average); the actual time was 1 minute 47 seconds (range, 1:19
      2:25 minutes). The extrapolated cumulative order entry time was 26 hours 38
      minutes of physician time in the 6-month period after computerized physician
      order entry was started. Most of the survey respondents (98%, 41/42) did not
      think radiologist order entry improved patient safety, and 43% (18/42) believed
      it to be very or extremely disruptive. CONCLUSION: Mandatory radiologist
      performed electronic order entry does not negatively affect the rate of use of
      oral contrast for inpatient abdominopelvic CT, but it is potentially time
      consuming and disliked by participating radiologists.

PMID- 22358002
TI  - Variation in tube voltage for adult neck MDCT: effect on radiation dose and image
      quality.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of peak kilovoltage
      on radiation dose and image quality in adult neck MDCT. MATERIALS AND METHODS: An
      anthropomorphic phantom with metal oxide semiconductor field effect transistor
      detectors was imaged with a 64-MDCT scanner. The reference CT protocol called for
      120 kVp, and images obtained with that protocol were compared with CT images
      obtained with protocols entailing 80, 100, and 140 kVp. All imaging was performed
      with automatic tube current modulation. Organ dose and effective dose were
      determined for each protocol and compared with those obtained with the 120-kVp
      protocol. Image noise was evaluated objectively and subjectively for each
      protocol. RESULTS: The highest organ doses for all protocols were to the thyroid,
      ocular lens, skin, and mandible. The greatest reductions in organ dose were for
      the bone marrow of the cervical spine and mandible: 43% and 35% with the 100-kVp
      protocol and 63% and 53% with the 80-kVp protocol. Effective dose decreased as
      much as 9% with the 100-kVp protocol and 12% with the 80-kVp protocol. Use of the
      140-kVp protocol was associated with an increase in organ dose as high as 64% for
      bone marrow in the cervical spine and a 19% increase in effective dose. Image
      noise increased with lower peak kilovoltage. The measured noise difference was
      greatest at 80 kVp, absolute increases were less than 2.5 HU. There was no
      difference in subjective image quality among protocols. CONCLUSION: Reducing the
      voltage from 120 to 80 kVp for neck CT can result in greater than 50% reduction
      in the absorbed organ dose to the bone marrow of the cervical spine and mandible
      without impairment in subjective image quality.

PMID- 22358003
TI  - Reducing the rate of repeat imaging: import of outside images to PACS.
AB  - OBJECTIVE: Repeat imaging at the transfer of care between institutions is a
      potential source of overutilization. The purpose of this study was to assess
      whether importing images obtained at one institution to the PACS at another
      institution reduces the number of repeat imaging examinations performed, sparing
      patients unnecessary cost and radiation. MATERIALS AND METHODS: Informed consent
      was waived for this retrospective study, which included 267 patients who had
      undergone CT or MRI of the abdomen at our or another institution within 4 months
      before transarterial chemoembolization. Patients were divided into the following
      four groups based on the availability of their images from institutions other
      than ours (outside images): outside imaging performed but images not available;
      outside images available on CD or film but not imported; outside images imported
      to PACS; and no outside imaging, that is, all imaging performed at our
      institution. The rates of repeat imaging in the four groups were compared.
      RESULTS: When outside images were not available, 72% (13/18) of patients
      underwent repeat imaging; when outside images were available but not imported,
      52% (14/27); when outside images were imported to PACS, 11% (9/79); and when
      imaging was performed only at our institution, 13% (18/143). Patients whose
      outside images were imported were significantly less likely to undergo repeat
      imaging than were both groups whose outside images were not imported (p < 0.001),
      and their rate of repeat imaging was similar to that of patients who did not
      undergo outside imaging (p = 0.79). After adjustment for potential confounders,
      including age, sex, referring institution, and size and number of lesions, the
      odds that a patient whose images were imported would undergo repeat imaging were
      significantly lower than those of a patient whose outside images were not
      imported (odds ratios, 31 for images not available and 9.0 for images available
      but not imported; both p < 0.001) and were similar to those of a patient who
      underwent all imaging at our institution (odds ratio, 0.71; p = 0.51).
      CONCLUSION: Importing outside images to PACS reduces the rate of repeat imaging.

PMID- 22358004
TI  - MDCT arthrography of the shoulder with datasets of isotropic resolution:
      indications, technique, and applications.
AB  - OBJECTIVE: The purposes of this review are to summarize the indications for MDCT
      arthrography of the shoulder, highlight the features of MDCT acquisition, and
      describe the normal and abnormal MDCT arthrographic appearances of the shoulder.
      CONCLUSION: MDCT arthrography is a valid alternative for shoulder imaging of
      patients with contraindications to MRI or after failed MRI. MDCT arthrography is
      accurate for assessment of a variety of shoulder abnormalities and, with further
      validation, may become the imaging test of choice for evaluation of the
      postoperative shoulder.

PMID- 22358005
TI  - Imaging of limb salvage surgery.
AB  - OBJECTIVE: Limb salvage surgery comprises surgical techniques designed to resect
      musculoskeletal extremity tumors and subsequently reconstruct a limb with an
      acceptable oncologic, functional, and cosmetic result. Today, 70-90% of malignant
      extremity tumors are being treated with limb salvage surgery. CONCLUSION: The
      purpose of this article is to describe the operative techniques, review the
      imaging techniques, and to illustrate imaging findings related to the surgeries
      in complicated and uncomplicated cases.

PMID- 22358006
TI  - Preoperative imaging of anterior shoulder instability: diagnostic effectiveness
      of MDCT arthrography and comparison with MR arthrography and arthroscopy.
AB  - OBJECTIVE: The purpose of this article is to assess the diagnostic effectiveness
      of MDCT arthrography in the preoperative planning of anterior shoulder
      instability compared with MR arthrography and arthroscopy. SUBJECTS AND METHODS:
      Shoulder MDCT arthrography and MR arthrography examinations prospectively
      performed in 40 consecutive patients (30 male and 10 female patients; mean age,
      26 years) were independently evaluated by two musculoskeletal radiologists who
      were blinded to the arthroscopic findings, which represented the reference
      standard. Sensitivity, specificity, and agreement with arthroscopy were
      determined for osseous, cartilage, and labroligamentous injuries. RESULTS: In
      detecting glenoid rim fractures, MDCT arthrography had a sensitivity of 100%
      (12/12), a specificity of 96% (27/28), and better agreement with surgery (kappa =
      0.94) than did MR arthrography (kappa = 0.74). For the depiction of glenoid
      cartilage lesions, MDCT arthrography had a sensitivity of 82% (18/22), a
      specificity of 89% (16/18), and slightly better agreement with surgery (kappa =
      0.70) than did MR arthrography (kappa = 0.66). In identifying anterior labral
      periosteal sleeve avulsion lesions, MDCT arthrography had a sensitivity of 93%
      (26/28), a specificity of 100% (12/12), and better agreement with surgery (kappa
      = 0.89) than did MR arthrography (kappa = 0.74). For the diagnosis of humeral
      avulsion of the inferior glenohumeral ligament lesions, MDCT arthrography had a
      sensitivity and a specificity of 100% (2/2) and better agreement with surgery
      (kappa = 1) than did MR arthrography (kappa = 0.79). CONCLUSION: MDCT
      arthrography showed better accuracy than did MR arthrography in the detection of
      osseous, cartilage, and labroligamentous injuries related to anterior shoulder
      instability. Because MDCT arthrography was particularly reliable for the
      detection of glenoid rim fractures and humeral avulsion of the inferior
      glenohumeral ligament lesions, which represent crucial findings in the
      preoperative planning, this technique may beneficially affect treatment by means
      of selecting the proper surgical treatment.

PMID- 22358007
TI  - BRAF mutation analysis and sonography as adjuncts to fine-needle aspiration
      cytology of papillary thyroid carcinoma: their relationships and roles.
AB  - OBJECTIVE: The objective of our study was to evaluate the relationships between
      BRAF mutation status, sonography findings, and fine-needle aspiration cytology
      features in patients with papillary thyroid carcinoma (PTC) and to evaluate the
      diagnostic merits of BRAF mutation status and sonography findings as adjuncts to
      cytologic diagnoses. MATERIALS AND METHODS: From March 2006 through June 2008,
      clinicopathologic factors, sonography findings, cytology results, and BRAF
      mutation status were evaluated in 524 patients (437 women and 87 men) with 553
      thyroid nodules; of the 170 malignant nodules, 164 were PTCs. Clinicopathologic
      factors, sonography findings, and cytology results were correlated with BRAF
      status. The diagnostic sensitivities and specificities of sonography, cytology,
      and BRAF analysis and their combinations were compared. RESULTS: The V600E
      mutation of BRAF (BRAF(V600E)) was detected in 141 of 170 malignant thyroid
      nodules (82.9%) (140 PTCs and one follicular variant of PTC). Multiple logistic
      regression revealed that BRAF status was not associated with sonography features
      with the exception of a negative relation between BRAF(V600E) and an irregular
      shape (p = 0.004). An indeterminate cytology result was more frequent for BRAF
      negative PTC than BRAF-positive PTC (p = 0.035). By adding BRAF status to
      cytology, diagnostic sensitivity for PTC was significantly increased (94.1%) as
      compared with cytology alone (81.8%) (p < 0.001). The triple combination-that is,
      sonography, cytology, and BRAF analysis-showed higher sensitivity than BRAF plus
      cytology (98.2% vs 94.1%, respectively) (p < 0.05). CONCLUSION: The sonography
      features of PTC, other than an irregular shape, are not related to BRAF status
      and the combination of sonography and BRAF testing would increase the diagnostic
      accuracy of cytologic diagnoses of PTC.

PMID- 22358008
TI  - Technique for CT fluoroscopy-guided cervical interlaminar steroid injections.
AB  - OBJECTIVE: We describe the use of CT fluoroscopy as a guidance tool for
      performing interlaminar epidural steroid injections in the cervical spine.
      CONCLUSION: CT fluoroscopy is an alternative method to perform cervical
      interlaminar steroid injections that allows precise needle placement in the
      epidural space.

PMID- 22358009
TI  - Spectrum of malignant pleural and pericardial disease on FDG PET/CT.
AB  - OBJECTIVE: The purpose of this article is to illustrate a wide spectrum of
      malignant primary and secondary pleural and pericardial diseases imaged with
      (18)F-FDG PET/CT. CONCLUSION: A wide variety of malignant pleural and pericardial
      diseases can be detected, staged, and monitored by FDG PET/CT. Although the
      PET/CT findings are often nonspecific, the aim of this atlas is to show that the
      spectrum of pleural and pericardial disease that can be evaluated with PET/CT is
      much broader than current literature would suggest. PET/CT readers and
      oncologists should be aware of the wide variety of malignancies that can affect
      the pleura and pericardium and some of the patterns of FDG uptake that can be
      observed in these cases.

PMID- 22358011
TI  - Chemoembolization practice patterns and technical methods among interventional
      radiologists: results of an online survey.
AB  - OBJECTIVE: The objective of our study was to assess patterns of chemoembolization
      use; identify variations in application, technique, and follow-up; and recognize
      areas of practice conformity and divergence. MATERIALS AND METHODS: During August
      and September 2010, Society of Interventional Radiology (SIR) members with
      "chemoembolization expertise" were invited to participate in an anonymous online
      questionnaire. RESULTS: Two hundred sixty-eight of 1157 invited SIR members (23%)
      answered the 34-item survey. Respondents were predominantly male (93%) fellowship
      trained full-time interventional radiologists (IRs) (87%) in practice for less
      than 15 years (69%) at community hospitals (61%) in the United States (91%). IRs
      (53%) most commonly drove therapeutic decision making. Most respondents (61%)
      performed 1-5 chemoembolizations per month and preferred drug-eluting beads to
      iodized oil for unifocal (46% vs 39%, respectively) and multifocal (40% vs 30%)
      hepatocellular carcinoma (HCC), although (90)Y radioembolization was favored when
      portal vein thrombosis was present (48% vs 28%). IRs showed variability in
      recognized procedure contraindications. Most respondents agreed on
      chemotherapeutic regimen but showed variable particle embolization use (17-45%)
      during oily chemoembolization. The 100- to 300-MUm (49%) LC Beads (AngioDynamics)
      (65%) were the favored drug-eluting beads. Lobar chemoembolization was preferred.
      Treatment endpoints lacked consensus, but substasis was most desirable (56%). Up
      to 19% of respondents performed outpatient chemoembolization. Concurrent
      percutaneous ablation was infrequently used (applied in 0-25% of cases by 61-91%
      of respondents). Most (up to 74%) IRs preferred CT follow-up with the decision
      for retreatment based on CT evidence of viable disease (93%). CONCLUSION:
      Variability in chemoembolization practice exists among IRs. Continued
      investigation of treatment strategies and devices is necessary to better optimize
      and standardize transcatheter therapies for liver tumors.

PMID- 22358010
TI  - Time-resolved MR angiography of the legs at 3 T using a low dose of gadolinium:
      initial experience and contrast dynamics.
AB  - OBJECTIVE: This article describes our initial clinical experience with time
      resolved MR angiography (MRA) of the legs using the time-resolved imaging with
      stochastic trajectories (TWIST) technique with a half dose of gadolinium.
      MATERIALS AND METHODS: Thirty-four patients underwent a TWIST examination of the
      legs at 3 T. Thirty-three patients also underwent a bolus-chase MRA examination
      in the same setting. Times elapsed between the start of contrast injection and
      the appearance of contrast material (t(A)) and peak enhancement of the arteries
      in the legs (t(B)) were analyzed. The number of patients with examinations
      affected by venous contamination was determined. The differences in t(A) and t(B)
      between cases in which venous contamination was present or absent were evaluated
      using a two-tailed Student t test. RESULTS: The TWIST technique using a half dose
      of gadolinium provided diagnostic-quality images of all patients. The mean t(A)
      was 35.5 +/- 8.8 (SD) seconds (range, 17.8-60.4 seconds), and the mean t(B) was
      59.1 +/- 15.1 seconds (range, 31-98.8 seconds). Venous contamination was observed
      in bolus-chase MRA images of 52.9% of patients. The relationship between venous
      contamination and t(A) was not statistically significant (p = 0.13). The
      incidence of venous contamination was higher in patients with lower values of
      t(B) (p = 0.01). CONCLUSION: The described low-dose clinical experience with
      TWIST and the contrast dynamics information gained from this study could aid
      radiologists in planning protocols for leg MRA examinations.

PMID- 22358012
TI  - Primary and metastatic vascular neoplasms: imaging findings.
AB  - OBJECTIVE: The purpose of this article is to review the imaging findings of
      vascular tumors. CONCLUSION: Tumors of the vasculature are a pervasive disease
      entity consisting of both primary and metastatic lesions. Cross-sectional imaging
      plays a pivotal role in the diagnosis and delineation of the extent of this
      entity. Recognition of the characteristic imaging presentation of each tumor at
      CT and MRI can facilitate prompt diagnosis and accurate staging.

PMID- 22358013
TI  - Mammography and the risk of thyroid cancer.
AB  - OBJECTIVE: The purpose of this article is to discuss recent media reports that
      have suggested a link between mammography and increased incidence of thyroid
      cancer in women. Those reports have caused many requests that a thyroid shield be
      used during mammography. CONCLUSION: On the basis of a previously published study
      that investigated organ doses from mammography and of cancer risk estimates using
      the seventh Biologic Effects of Ionizing Radiation report, we contend that
      thyroid shielding during mammography is unnecessary and may increase retakes
      rather than afford radiation protection of the thyroid.

PMID- 22358014
TI  - Clinically missed cancer: how effectively can radiologists use computer-aided
      detection?
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness with
      which radiologists can use computer-aided detection (CADe) to detect cancer
      missed at screening. MATERIALS AND METHODS: An observer study was performed to
      measure the ability of radiologists to detect breast cancer on mammograms with
      and without CADe. The images in the study were from 300 analog mammographic
      examinations. In 234 cases the mammograms were read clinically as normal and free
      of cancer for at least 2 subsequent years. In the other 66 cases, cancers were
      missed clinically. In 256 cases, current and previous mammograms were available.
      Eight radiologists read the dataset and recorded a BI-RADS assessment, the
      location of the lesion, and their level of confidence that the patient should be
      recalled for diagnostic workup for each suspicious lesion. Jackknife alternative
      free-response receiver operating characteristic analysis was used. RESULTS: The
      jackknife alternative free-response receiver operating characteristic figure of
      merit was 0.641 without aid and 0.659 with aid (p = 0.06; 95% CI, -0.001 to
      0.036). The sensitivity increased 9.9% (95% CI, 3.4-19%) and the callback rate
      12.1% (95% CI, 7.3-20%) with CADe. Both increases were statistically significant
      (p < 0.001). Radiologists on average ignored 71% of correct computer prompts.
      CONCLUSION: Use of CADe can increase radiologist sensitivity 10% with a
      comparable increase in recall rate. There is potential for CADe to have a bigger
      clinical impact because radiologists failed to recognize a correct computer
      prompt in 71% of missed cancer cases [corrected].

PMID- 22358015
TI  - Diffusion-weighted imaging of breast masses: comparison of diagnostic performance
      using various apparent diffusion coefficient parameters.
AB  - OBJECTIVE: The purpose of our study was to assess the utility of the minimum
      apparent diffusion coefficient (ADC), average ADC, maximum ADC, and ADC
      difference value and to find optimum ADC parameters for differentiation between
      benign and malignant lesions in breast diffusion-weighted imaging (DWI).
      MATERIALS AND METHODS: Sixty-seven women with 75 masslike lesions (27 benign, 48
      malignant) were examined with 3-T MRI. To assess heterogeneity within the lesion,
      the difference between minimum and maximum ADCs was recorded as the ADC
      difference value. Diagnostic performances of these parameters were compared by
      receiver operating characteristic (ROC) curve analysis. RESULTS: Each ADC
      parameter showed significant differences between malignant and benign lesions.
      The optimal cutoff levels for differentiating benign versus malignant lesions
      were determined by identifying the points where the sensitivity and specificity
      were equal on the ROC curves. According to ROC analyses, the following
      sensitivities and specificities were obtained: average ADC, 75.6% and 75.6%;
      minimum ADC, 85.5% and 85.5%; maximum ADC, 63.5% and 63.5%; ADC difference value,
      70.1% and 70.1%. Minimum ADC had the largest area under the ROC curve (AUC) of
      0.93. Minimum ADC combined with the ADC difference value improved the AUC to
      0.95, with sensitivity and specificity of 89.1% and 89.1%. CONCLUSION: Minimum
      ADC may be an optimal DWI single parameter for differentiation between malignant
      and benign lesions of breast masses. Furthermore, the combination of the minimum
      ADC and ADC difference value significantly elevated diagnostic performance of
      breast DWI in comparison with average ADC.

PMID- 22358016
TI  - Mammography screening: a new estimate of number needed to screen to prevent one
      breast cancer death.
AB  - OBJECTIVE: The purpose of our study was to estimate the number of women needed to
      screen (NNS) to prevent one breast cancer death and the number needed to screen
      per life-year gained (NNS/LYG) with annual or biennial screening mammography and
      to compare NNS to the number needed to invite (NNI) to a screening trial to
      prevent one breast cancer death. MATERIALS AND METHODS: Cancer Intervention and
      Surveillance Modeling Network (CISNET) modeling results commissioned by the
      United States Preventive Services Task Force (USPSTF) for their 2009 update of
      breast cancer screening recommendations were used to estimate NNS and NNS/LYG
      with annual or biennial screening mammography. NNS values were compared with NNI
      as reported by USPSTF, which used the CISNET results to aid their 2009
      recommendation of starting age and screening interval. RESULTS: For women between
      the ages of 40 and 49 years undergoing annual screening mammography, CISNET
      modeling results estimate an NNS of 746, 39% of the NNI of 1904 estimated by
      USPSTF on the basis of randomized controlled trial (RCT) data. The NNS based on
      CISNET results for women between 50 and 59 years is 351 (26% of the NNI of 1339
      estimated by USPSTF from RCT data), for women between 60 and 69 years is 233 (62%
      of the NNI of 377 estimated by USPSTF from RCT data), and for women between 70
      and 79 years is 377. Annual screening of women between 40 and 84 years yields an
      NNS of 84 and an NNS/LYG of 5.3. Biennial screening of women ages 50-74 yields an
      NNS of 144 and an NNS/LYG of 9.1. CONCLUSION: The NNS based on CISNET modeling
      results is much smaller than the NNI based on RCT data. Eighty-four women need to
      be screened annually between 40 and 84 years to save one life from breast cancer
      and 5.3 need to be screened annually to gain 1 life-year from breast cancer.

PMID- 22358017
TI  - Mediastinal masses in children.

PMID- 22358018
TI  - Inflammatory pseudotumor: the great mimicker.
AB  - OBJECTIVE: The purpose of this review is to describe the pathophysiologic
      findings, differential diagnosis, imaging features, and management of
      inflammatory pseudotumor in various locations throughout the body. CONCLUSION:
      Inflammatory pseudotumor is a rare benign process mimicking malignant processes
      and has been found in almost every organ system. Radiologists should be familiar
      with this entity as a diagnostic consideration to avoid unnecessary surgery.

PMID- 22358019
TI  - Use of maximum slope images generated from dynamic contrast-enhanced MRI to
      detect locally recurrent prostate carcinoma after prostatectomy: a practical
      approach.
AB  - OBJECTIVE: The purpose of this article is to present the value of high-temporal
      resolution and high-spatial-resolution dynamic contrast-enhanced MRI (DCE-MRI)
      combined with the postprocessed slope images generated from the fastest rate of
      enhancement of each voxel for detecting local recurrence of prostate carcinoma
      after radical prostatectomy. METHODS AND MATERIALS: Of 125 patients, 47 patients
      with and without local recurrence confirmed by biopsy or clinical follow-up were
      identified. All patients underwent DCE-MRI with a spatial resolution of 3 mm and
      mean temporal resolution of 11.3 seconds (range, 8.4-14.0 seconds). RESULTS: In
      patients with local recurrence, the mean (+/- SD) prostate-specific antigen level
      and tumor size were 1.9 +/- 1.8 mg/dL and 10.8 +/- 5.7 mm, respectively, at the
      time of MRI. Thirty-six of 37 patients (97%) with biopsy or clinically confirmed
      local recurrence had positive MRI findings. Eight of 10 patients (80%) with
      negative recurrence had negative MRI findings. Of the 36 patients, 16 (44%) had
      time-intensity curves of rapid increase-rapid washout and 18 (50%) had rapid
      increase-plateau or slow washout. The recurrent tumor reached the peak
      enhancement within one phase following the peak enhancement of the common femoral
      artery. In patients with a negative MRI result, the mean PSA level was 0.2 +/-
      0.1 mg/dL. CONCLUSION: DCE-MRI using high temporal and spatial resolution is
      highly accurate in detecting subcentimeter local recurrences within the
      postprostatectomy bed. Combined with visual inspection of original source images
      (using the common femoral artery as a reference), the slope image is a simple and
      practical way of identifying locally recurrent prostate carcinoma.

PMID- 22358020
TI  - The epiphyseal torsion angle in MR arthrography of the hip: diagnostic utility in
      patients with femoroacetabular impingement syndrome.
AB  - OBJECTIVE: The purpose of the study was to evaluate whether patients with
      clinically suspected femoroacetabular impingement (FAI) show higher epiphyseal
      torsion angle values on MR arthrography than healthy volunteers. Another
      objective was to estimate whether patients with increased epiphyseal torsion
      angles show a higher incidence of hip abnormalities or a higher incidence of
      increased alpha angles on MR arthrography than patients with an epiphyseal
      torsion angle considered normal. MATERIALS AND METHODS: Sixty-eight consecutive
      patients with clinically suspected FAI, no history of hip surgery, and MR
      arthrography of the hip performed at our institution were included in the study
      group. The control group included 50 standard MR examinations of the hip of 25
      healthy volunteers with negative findings on a clinical impingement test.
      Epiphyseal torsion angles and alpha angles were measured independently by three
      radiologists. Furthermore, MR arthrograms were retrospectively evaluated by two
      radiologists in consensus for hip abnormalities associated with FAI. RESULTS: The
      epiphyseal torsion angles were significantly higher in the study group than the
      control group for all three readers (reader 1, p = 0.001; reader 2, p = 0.003;
      reader 3, p = 0.045). There was no statistical correlation between increased
      epiphyseal torsion angles and pathologic alpha angles (readers 1-3: p = 0.199, p
      = 0.343, p = 0.058, respectively). Patients with increased epiphyseal torsion
      angles did not show a higher incidence of labral abnormalities than patients with
      epiphyseal torsion angles considered normal (readers 1-3: p = 0.335, p = 0.383, p
      = 0.676). CONCLUSION: Patients with clinically suspected FAI show increased
      epiphyseal torsion angles compared with healthy volunteers. Values greater than
      20 degrees  should be considered pathologic. A pathologic retrotorsion of the
      femoral epiphysis may play a role in developing hip pain related to FAI and
      premature osteoarthritis.

PMID- 22358021
TI  - The utility of ultrasound elastography and MicroPure imaging in the
      differentiation of benign and malignant thyroid nodules.
AB  - OBJECTIVE: The aim of this study was to evaluate the utility of ultrasound
      elastography and MicroPure imaging in the differential diagnosis of benign and
      malignant thyroid nodules. SUBJECTS AND METHODS: A total of 74 consecutive
      patients (65 women and nine men; age range, 21-80 years; mean [+/- SD] age, 51 +/
      12.7 years) with thyroid nodules, who were referred for fine-needle aspiration
      biopsy by endocrinology or general surgery clinics, were prospectively examined
      using B-mode ultrasound, ultrasound elastography, and MicroPure imaging. The
      strain value ratio (strain index) of thyroid nodules was calculated. Patients
      with malignant or intermediate fine-needle aspiration biopsy results underwent
      thyroid surgery. RESULTS: Using MicroPure imaging, 17 of 65 benign thyroid
      nodules (26.6%) and three of nine malignant thyroid nodules (33.3%) were found to
      contain microcalcifications. The sensitivity, specificity, negative predictive
      value, positive predictive value, and the accuracy rate of MicroPure imaging were
      42.9%, 80.6%, 93.1%, 18.8%, and 77%, respectively. By using receiver operating
      characteristic analysis, the best cutoff point (2.31) was computed (area under
      the curve, 0.87; p < 0.001). The sensitivity, specificity, negative predictive
      value, positive predictive value and accuracy rate of the strain index values
      were 85.7%, 82.1%, 98.2%, 33.3%, and 82.4%, respectively, when the best cutoff
      point of 2.31 was used (p = 0.001). The p value (x = malign) was 0.96 for a
      strain index value higher than 2.31. CONCLUSION: This preliminary study indicated
      that ultrasound elastography and MicroPure imaging can be used for the
      differentiation of benign and malignant thyroid nodules.

PMID- 22358022
TI  - Rapid pediatric cardiac assessment of flow and ventricular volume with compressed
      sensing parallel imaging volumetric cine phase-contrast MRI.
AB  - OBJECTIVE: The quantification of cardiac flow and ventricular volumes is an
      essential goal of many congenital heart MRI examinations, often requiring
      acquisition of multiple 2D phase-contrast and bright-blood cine steady-state free
      precession (SSFP) planes. Scan acquisition, however, is lengthy and highly
      reliant on an imager who is well-versed in structural heart disease. Although it
      can also be lengthy, 3D time-resolved (4D) phase-contrast MRI yields global flow
      patterns and is simpler to perform. We therefore sought to accelerate 4D phase
      contrast and to determine whether equivalent flow and volume measurements could
      be extracted. MATERIALS AND METHODS: Four-dimensional phase contrast was modified
      for higher acceleration with compressed sensing. Custom software was developed to
      process 4D phase-contrast images. We studied 29 patients referred for congenital
      cardiac MRI who underwent a routine clinical protocol, including cine short-axis
      stack SSFP and 2D phase contrast, followed by contrast-enhanced 4D phase
      contrast. To compare quantitative measurements, Bland-Altman analysis, paired
      Student t tests, and F tests were used. RESULTS: Ventricular end-diastolic, end
      systolic, and stroke volumes obtained from 4D phase contrast and SSFP were well
      correlated (rho = 0.91-0.95; r(2) = 0.83-0.90), with no statistically significant
      difference. Ejection fractions were well correlated in a subpopulation that
      underwent higher-resolution compressed-sensing 4D phase contrast (rho = 0.88;
      r(2) = 0.77). Four-dimensional phase contrast and 2D phase contrast flow rates
      were also well correlated (rho = 0.90; r(2) = 0.82). Excluding ventricles with
      valvular insufficiency, cardiac outputs derived from outlet valve flow and stroke
      volumes were more consistent by 4D phase contrast than by 2D phase contrast and
      SSFP. CONCLUSION: Combined parallel imaging and compressed sensing can be applied
      to 4D phase contrast. With custom software, flow and ventricular volumes may be
      extracted with comparable accuracy to SSFP and 2D phase contrast. Furthermore,
      cardiac outputs were more consistent by 4D phase contrast.

PMID- 22358023
TI  - High-powered gas-cooled microwave ablation: shaft cooling creates an effective
      stick function without altering the ablation zone.
AB  - OBJECTIVE: The purpose of our study was to validate the ability of a new gas
      cooled microwave device to secure antennas into tissue before ablation via shaft
      cooling and to verify that such cooling does not compromise the intended
      ablation. MATERIALS AND METHODS: The force required to extract several types of
      applicators from ex vivo bovine liver before and after ablation was measured. Six
      groups were compared: cooled needle and multitined radiofrequency electrodes,
      secured and unsecured cryoprobes, and gas-cooled microwave antennas (n = 6 each).
      Ablations were next created in in vivo porcine livers for 2 and 10 minutes (n = 6
      each) using the gas-cooled microwave system at 140 W. Extraction force was again
      measured before and after ablation and compared between groups using analysis of
      variance with post hoc Student t tests. Histologic analysis of the ablation zone
      was performed to evaluate cellular necrosis along the antenna shaft. RESULTS: Ex
      vivo, the secured cryoprobe and microwave antenna required significantly more
      force to remove than unsecured radiofrequency, cryoprobe, and microwave
      applicators (p < 0.05, all comparisons). The multitined radiofrequency electrode
      and cooled radiofrequency electrode required significantly more force to remove
      after ablation than before ablation (p = 0.006 and 0.02, respectively). In vivo,
      the secured antenna required significantly more force to remove before ablation
      than after ablation at both 2 (p < 0.0001) and 10 minutes (p < 0.0001). There was
      no histologic evidence of cell preservation along the antenna shaft. CONCLUSION:
      The gas cooling used in this microwave device can effectively secure antennas
      into tissue without altering ablation shape or reducing the intended thermal
      damage.

PMID- 22358024
TI  - Augmented reality visualization with image overlay for MRI-guided intervention:
      accuracy for lumbar spinal procedures with a 1.5-T MRI system.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the accuracy
      of an augmented reality image overlay system in MRI-guided spinal injection
      procedures. MATERIALS AND METHODS: An augmented reality prototype was used in
      conjunction with a 1.5-T MRI system. A human lumbar spine phantom was used in
      which 62 targets were punctured to assess the accuracy of the system. Sixty
      anatomic targets (facet joint, disk space, and spinal canal) were punctured to
      assess how the accuracy of the system translated into practice. A visualization
      software interface was used to compare planned needle paths and final needle
      locations on coregistered CT images (standard of reference). Outcome variables
      included entry error, angle error, depth error, target error, successful access
      of anatomic targets, number of needle adjustments, and time requirements.
      RESULTS: Accuracy assessments showed entry error of 1.6 +/- 0.8 mm, angle error
      of 1.6 degrees  +/- 1.0 degrees , depth error of 0.7 +/- 0.5 mm, and target error
      of 1.9 +/- 0.9 mm. All anatomic targets (60 of 60 insertions) were successfully
      punctured, including all 20 facet joints, all 20 disks, and all 20 spinal canals.
      Four needle adjustments (6.7%) were required. Planning of a single needle path
      required an average of 55 seconds. A single needle insertion required an average
      of 1 minute 27 seconds. CONCLUSION: The augmented reality image overlay system
      evaluated facilitated accurate MRI guidance for successful spinal procedures in a
      lumbar spine model. It exhibited potential for simplifying the current practice
      of MRI-guided lumbar spinal injection procedures.

PMID- 22358025
TI  - A novel method of punctured Miller-Abbott tube placement using a guidewire under
      fluoroscopic guidance.
AB  - OBJECTIVE: The purpose of this article is to evaluate the usefulness of a new
      technique for placing Miller-Abbott tubes in patients with small-bowel
      obstruction. SUBJECTS AND METHODS: The Miller-Abbott tube was placed in 10
      patients by use of the conventional method (group A) and in 11 patients with a
      punctured Miller-Abbott tube with the use of guidewire (group B). Technical
      success was defined as insertion of the tube into the duodenum beyond the pylorus
      of the stomach in group A and into the jejunum beyond the Treitz ligament in
      group B. Clinical success was defined as intestinal decompression and relief of
      obstructive symptoms. We evaluate the correlations between the cause of
      obstruction and the end results. RESULTS: The success rate of the tube placement
      was 40% (4/10) in group A and 100% (11/11) in group B. Clinical success of tube
      placement was achieved in five of 10 patients (50.0%) in group A and in nine of
      11 patients (81.8%) in group B. Carcinomatosis was associated with significantly
      decreased clinical success rates in both groups (p = 0.038 in group A; p = 0.039
      in group B). The mean (+/- SD) procedure time for placement of the Miller-Abbott
      tube was 35.8 +/- 8.13 minutes in group A and 15.3 +/- 5.93 minutes in group B,
      with a statistically significant difference (p < 0.001). CONCLUSION: The new
      technique of placing a punctured Miller-Abbott tube with the use of a guidewire
      enables the tube to pass through the pylorus and the Treitz ligament while
      significantly reducing the procedure time, with no clinical disadvantages caused
      by the puncture site.

PMID- 22358026
TI  - Takayasu arteritis: intravascular contrast medium for MR angiography in the
      evaluation of disease activity.
AB  - OBJECTIVE: Takayasu arteritis is difficult to diagnose, and the evaluation of
      disease activity is even more challenging. Laboratory, clinical, and radiologic
      criteria are limited indicators of disease activity. Gadofosveset trisodium is a
      recently introduced intravascular contrast agent. In this study we sought to
      investigate a correlation between clinical activity and enhancement of vascular
      wall thickening in patients with Takayasu arteritis who underwent MR angiography
      with gadofosveset. SUBJECTS AND METHODS: Twenty-three consecutively registered
      patients (21 women, two men) with Takayasu arteritis underwent MR angiography of
      the supraaortic trunks, aorta, and visceral vessels. Intravascular contrast
      medium was used to correlate thickened vessel wall enhancement with clinical
      criteria of disease activity. ECG-triggered black-blood first-pass high
      resolution steady-state imaging was performed for all patients. RESULTS: Before
      MR angiography, 14 patients were considered to have active disease. Heterogeneous
      structural involvement of the vascular tree was found. Twenty of 23 patients
      (87.0%) had supraaortic trunk involvement, including 12 of the 14 patients
      (85.7%) with active disease. Seventeen of the 23 patients (73.9%) had aortic and
      visceral vessel involvement, including 12 of the 14 patients (85.7%) with active
      disease. On steady state images in the active disease group, the mean signal-to
      noise-ratio increased from 17.4 to 35.3 after gadofosveset injection (p >
      0.0001), while in the nonactive disease group it increased from 52.8 to 69.6 (p =
      0.08). A cutoff of 40% was best for differentiating active from inactive disease
      (sensitivity, 100%; specificity, 89%; positive predictive value, 92%; negative
      predictive value, 100%). CONCLUSION: Use of intravascular contrast medium
      significantly increases the effectiveness of MR angiography in differentiating
      active and inactive disease.

PMID- 22358027
TI  - Analysis by MRI of residual tumor after radiofrequency ablation for early stage
      breast cancer.
AB  - OBJECTIVE: The objective of our study was to evaluate the effectiveness of MRI in
      the detection of possible residual lesions after radiofrequency ablation (RFA) in
      the treatment of breast cancer. SUBJECTS AND METHODS: We prospectively evaluated
      14 patients who had undergone ultrasound-guided core biopsies diagnostic of
      invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then
      ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary
      treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension
      and again 3 weeks after RFA to verify the presence of possible residual lesions.
      Conventional surgical resection of the tumors was performed 1 week after RFA. The
      MRI findings were compared with histopathologic analyses to confirm the presence
      or absence of residual tumor. RESULTS: There was no residual enhancement in seven
      lesions on the postablation breast MRI scans. These findings were confirmed by
      negative histopathologic findings in the surgical specimens. The MRI scans of
      five patients showed small areas of irregular enhancement that corresponded to
      residual lesions. In the two remaining patients, we observed enhancement of
      almost the entire lesion, indicating that RFA had failed. CONCLUSION: Breast MRI
      is effective in detecting residual lesions after RFA in patients with IDC.

PMID- 22358028
TI  - The relationship of mammographic density and age: implications for breast cancer
      screening.
AB  - OBJECTIVE: Breast density is increasingly recognized as an independent risk
      factor for the development of breast cancer, because it has been shown to be
      associated with a four- to sixfold increase in a woman's risk of malignant breast
      disease. Increased breast density as identified on mammography is also known to
      decrease the diagnostic sensitivity of the examination, which is of great concern
      to women at increased risk for breast cancer. Dense tissue has generally been
      associated with younger age and premenopausal status, with the assumption that
      breast density gradually decreases after menopause. However, the actual
      proportion of older women with dense breasts is unknown. The purpose of this
      study was to examine the relationship between age and breast density,
      particularly focusing on postmenopausal women. MATERIALS AND METHODS: All
      screening mammograms completed at the New York University Langone Medical Center
      in 2008 were retrospectively reviewed. Analysis of variance and descriptive
      analyses were used to evaluate the relationship between patient age and breast
      density. RESULTS: A total of 7007 screening mammograms were performed. The median
      age of our cohort was 57 years. Within each subgroup categorized by decade of
      age, there was a normal distribution among the categories of breast density.
      There was a significant inverse relationship between age and breast density (p <
      0.001). Seventy-four percent of patients between 40 and 49 years old had dense
      breasts. This percentage decreased to 57% of women in their 50s. However, 44% of
      women in their 60s and 36% of women in their 70s had dense breasts as
      characterized on their screening mammograms. CONCLUSION: In general, we found an
      inverse relationship between patient age and mammographic breast density.
      However, there were outliers at the extremes of age. A meaningful proportion of
      young women had predominantly fatty breasts and a subset of older women had
      extremely dense breasts. Increased density renders mammography a less sensitive
      tool for early detection. Breast density should be considered when evaluating the
      potential benefit of extended imaging for breast cancer screening, especially for
      women at increased risk for the disease.

PMID- 22358029
TI  - MRI features of ovarian fibroma and fibrothecoma with histopathologic
      correlation.
AB  - OBJECTIVE: The purpose of this article is to evaluate MRI features of ovarian
      fibroma and fibrothecoma with histopathologic correlation. MATERIALS AND METHODS:
      In this retrospective study, preoperative MRI examinations of 35 women (mean age,
      49 years; range, 24-86 years) with pathologically proven ovarian fibroma (n = 25)
      or fibrothecoma (n = 10) were reviewed by two radiologists in consensus. MRI
      features, including visibility of ovaries, presence of capsule, degeneration, T1
      and T2 signal, and enhancement pattern, were recorded and correlated with
      histopathologic features. After administration of gadopentetate dimeglumine, the
      maximum percentages of enhancement of fibroma or fibrothecoma, myometrium, and,
      if present, uterine fibroids (11/35 patients) were compared. RESULTS: All
      fibromas and fibrothecomas appeared well defined, with a mean size of 6.36 * 4.81
      cm. Ipsilateral and contralateral ovaries were each seen in 89% (31/35) of
      patients. Most fibromas and fibrothecomas were isointense to hypointense compared
      with myometrium on T1-weighted (91% [32/35]) and T2-weighted (77% [27/35])
      images. Capsule was noted in 63% (22/35) and degenerative changes were noted in
      66% (23/35) of patients. Fibromas and fibrothecomas larger than 6 cm more likely
      showed capsule (p < 0.0001, Fisher exact probability test), degenerative changes
      (p = 0.003), peripheral subcapsular cystic areas (p < 0.0001), heterogeneous T2
      signal (p = 0.001), and heterogeneous enhancement (p = 0.005). At least four of
      the above five characteristics were present in 93% (14/15) of fibromas and
      fibrothecomas larger than 6 cm (p < 0.0001). The maximum percentage of
      enhancement for fibromas and fibrothecomas (63%) was significantly lower than
      those for myometrium (131%; p < 0.0001) and fibroids (103%; p < 0.0001), without
      a statistically significant difference between the maximum percentage enhancement
      of myometrium and fibroids. A maximum percentage of enhancement less than 75%
      yielded 92% positive predictive value in differentiating fibromas and
      fibrothecomas from fibroids. Fibrothecomas had a higher maximum percentage of
      enhancement than did fibromas (p = 0.01). CONCLUSION: MRI features of ovarian
      fibromas and fibrothecomas depend on size, with capsule and degenerative changes
      common with fibromas and fibrothecomas larger than 6 cm. Fibromas and
      fibrothecomas enhance less than myometrium and fibroids do, and less than 75%
      maximum percentage enhancement can help in differentiating fibromas and
      fibrothecomas from fibroids.

PMID- 22358030
TI  - False-positive lesions mimicking breast cancer on FDG PET and PET/CT.
AB  - OBJECTIVE: Incidental (18)F-FDG-avid breast lesions are commonly encountered in
      patients with cancer who undergo staging PET/CT. This pictorial essay discusses
      breast lesions that show increased FDG activity, mimicking breast cancer, with
      biopsy-confirmed benign diagnosis. CONCLUSION: Acute and chronic inflammation,
      physiologic lactation, and benign breast masses, including silicone granuloma,
      fat necrosis, fibroadenoma, and postsurgical changes, may show increased FDG
      uptake on PET/CT. These conditions can often be differentiated from malignancy by
      correlative imaging, including mammography, sonography, or MRI.

PMID- 22358031
TI  - Professionalism and disclosing errors.

PMID- 22358032
TI  - Interruptive communication.

PMID- 22358033
TI  - Biopsy of major salivary gland masses.

PMID- 22358034
TI  - Optimal guidance technique for musculoskeletal biopsies.

PMID- 22358035
TI  - Why the United States should have virtopsied Osama Bin Laden.

PMID- 22358036
TI  - Hydrocolpos or hematocolpos?

PMID- 22358037
TI  - 16 for the price of 10: effects of a ban on multi-buy alcohol.
AB  - Multi-buy is one method by which retailers discount alcoholic beverage sales. It
      is common in the UK. A Scottish ban on multi-buys had an immediate impact on
      sales. Because other methods for lowering price as a marketing tool will be used,
      the longer-term impact is unknown. Legislating a minimum price per unit of
      alcohol may have a longer lasting effect on overall alcohol consumption.

PMID- 22358038
TI  - Price discounts on alcohol in a city in Northern England.
AB  - AIMS: To describe the extent and nature of price discounts on alcohol in
      Newcastle upon Tyne, England. METHODS: An observational survey in stores licensed
      for off-sales in December 2010 to January 2011. RESULTS: A total of 2018 price
      discounts in 29 stores led to a median saving of 25% and required a median
      purchase of 20 standard UK alcohol units. Median price per standard unit was
      L0.92 (US$1.49; ?1.05) before discount and L0.68 (US$1.10; ?0.78) after discount.
      CONCLUSIONS: Restriction of price discounting should be considered as a public
      health policy.

PMID- 22358039
TI  - The EpiCanvas infectious disease weather map: an interactive visual exploration
      of temporal and spatial correlations.
AB  - Advances in surveillance science have supported public health agencies in
      tracking and responding to disease outbreaks. Increasingly, epidemiologists have
      been tasked with interpreting multiple streams of heterogeneous data arising from
      varied surveillance systems. As a result public health personnel have experienced
      an overload of plots and charts as information visualization techniques have not
      kept pace with the rapid expansion in data availability. This study sought to
      advance the science of public health surveillance data visualization by
      conceptualizing a visual paradigm that provides an 'epidemiological canvas' for
      detection, monitoring, exploration and discovery of regional infectious disease
      activity and developing a software prototype of an 'infectious disease weather
      map'. Design objectives were elucidated and the conceptual model was developed
      using cognitive task analysis with public health epidemiologists. The software
      prototype was pilot tested using retrospective data from a large, regional
      pediatric hospital, and gastrointestinal and respiratory disease outbreaks were
      re-created as a proof of concept.

PMID- 22358040
TI  - Microsatellite markers for the relictual dove tree, Davidia involucrata
      (Cornaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the dove tree,
      Davidia involucrata (Cornaceae), a Tertiary relict currently endemic to China, to
      investigate its population genetics and phylogeography. METHODS AND RESULTS:
      Using the Fast Isolation by AFLP of Sequences Containing repeats (FIASCO)
      protocol, nine polymorphic microsatellite loci were identified and screened in 44
      individuals from three wild populations of D. involucrata. The number of alleles
      per locus ranged from two to three, while the observed heterozygosity and
      expected heterozygosity ranged from 0.0000 to 0.6000 and from 0.0000 to 0.6323,
      respectively. CONCLUSIONS: These new microsatellite loci will facilitate further
      studies of the population genetics and phylogeography of D. involucrata, as well
      as of the evolutionary history of the plant and other Tertiary relicts endemic to
      East Asia.

PMID- 22358041
TI  - Differential pollinator effectiveness and importance in a milkweed (Asclepias,
      Apocynaceae) hybrid zone.
AB  - PREMISE OF THE STUDY: Exceptions to the ideal of complete reproductive isolation
      between species are commonly encountered in diverse plant, animal, and fungal
      groups, but often the causative ecological processes are poorly understood. In
      flowering plants, the outcome of hybridization depends in part on the
      effectiveness of pollinators in interspecific pollen transport. In the Asclepias
      exaltata and A. syriaca (Apocynaceae) hybrid zone in Shenandoah National Park,
      Virginia, extensive introgression has been documented. The objectives of this
      study were to (1) determine the extent of pollinator overlap among A. exaltata,
      A. syriaca, and their hybrids and (2) identify the insect taxa responsible for
      hybridization and introgression. METHODS: We observed focal plants of parental
      species and hybrids to measure visitation rate, visit duration, and per-visit
      pollinia removal and deposition, and we calculated pollinator effectiveness and
      importance. KEY RESULTS: Visitation rates varied significantly between the 2 yr
      of the study. Overall, Apis mellifera, Bombus sp., and Epargyreus clarus were the
      most important pollinators. However, Bombus sp. was the only visitor that was
      observed to both remove and insert pollinia for both parent species as well as
      hybrids. CONCLUSIONS: We conclude that Bombus may be a key agent of hybridization
      and introgression in these sympatric milkweed populations, and hybrids are
      neither preferred nor selected against by pollinators. Thus, we have identified a
      potential mechanism for how hybrids act as bridges to gene flow between A.
      exaltata and A. syriaca. These results provide insights into the breakdown of
      prezygotic isolating mechanisms.

PMID- 22358042
TI  - Population genetic analysis of Bromus tectorum (Poaceae) indicates recent range
      expansion may be facilitated by specialist genotypes.
AB  - PREMISE OF THE STUDY: The mechanisms for range expansion in invasive species
      depend on how genetic variation is structured in the introduced range. This study
      examined neutral genetic variation in the invasive annual grass Bromus tectorum
      in the Intermountain Western United States. Patterns of microsatellite (SSR)
      genotype distribution in this highly inbreeding species were used to make
      inferences about the roles of adaptively significant genetic variation, broadly
      adapted generalist genotypes, and facultative outcrossing in the recent range
      expansion of B. tectorum in this region. METHODS: We sampled 20 individuals from
      each of 96 B. tectorum populations from historically and recently invaded
      habitats throughout the region and used four polymorphic SSR markers to
      characterize each individual. KEY RESULTS: We detected 131 four-locus SSR
      genotypes; however, the 14 most common genotypes collectively accounted for 79.2%
      of the individuals. Common SSR genotypes were not randomly distributed among
      habitats. Instead, characteristic genotypes sorted into specific recently invaded
      habitats, including xeric warm and salt desert as well as mesic high-elevation
      habitats. Other SSR genotypes were common across a range of historically invaded
      habitats. We observed very few heterozygous individuals (0.58%). CONCLUSIONS:
      Broadly adapted, generalist genotypes appear to dominate historically invaded
      environments, while recently invaded salt and warm desert habitats are dominated
      by distinctive SSR genotypes that contain novel alleles. These specialist
      genotypes are not likely to have resulted from recombination; they probably
      represent more recent introductions from unknown source populations. We found
      little evidence that outcrossing plays a role in range expansion.

PMID- 22358043
TI  - Development of microsatellite markers in Byrsonima crassifolia (Malpighiaceae).
AB  - PREMISE OF THE STUDY: We developed and characterized microsatellite markers for
      Byrsonima crassifolia (Malpighiaceae), a widely distributed neotropical fruit
      tree. METHODS AND RESULTS: Eight polymorphic and two monomorphic microsatellite
      loci were identified and screened in 60 samples from four geographically
      disparate populations (Bolivia, Brazil, Mexico, and Panama). Each locus exhibited
      between two and 11 alleles. Expected heterozygosity ranged from 0 to 0.839. All
      loci amplify in the congeners B. variabilis and B. basiloba, four amplify in B.
      bucidaefolia, and seven amplify in B. variabilis, although levels of polymorphism
      have not been assessed. CONCLUSIONS: These loci will provide novel tools for
      comparing genetic diversity present in cultivated and noncultivated populations
      of B. crassifolia throughout its range, and may prove valuable in related
      species.

PMID- 22358044
TI  - Microsatellite loci for Gossypium davidsonii (Malvaceae) and other D-genome,
      Sonoran Desert endemic cotton species.
AB  - PREMISE OF THE STUDY: Microsatellite primers previously developed for
      domesticated cotton (Gossypium hirsutum; tetraploid) were screened for their
      utility in investigating genetic structure and gene flow within G. davidsonii and
      five other wild, Mexican, D-genome cotton species (all diploid). METHODS AND
      RESULTS: We screened 50 microsatellite primer pairs from the Cotton Marker
      Database, identifying 10 loci as polymorphic within G. davidsonii. In genotyping
      approximately 200 individuals from four populations, we found that the number of
      alleles per locus ranged from seven to 17, and mean observed and expected
      heterozygosity ranged from 0.145 to 0.492 and from 0.436 to 0.734, respectively.
      We genotyped six to 20 individuals from each of the remaining species, finding
      these 10 loci to cross-amplify in all cases and in most cases to be polymorphic.
      CONCLUSIONS: These markers may be useful for further investigation of population
      genetics of G. davidsonii and other wild D-genome cotton species.

PMID- 22358045
TI  - Development and characterization of polymorphic microsatellite markers in
      Cyclobalanopsis glauca (Fagaceae).
AB  - PREMISE OF THE STUDY: We isolated and characterized polymorphic microsatellite
      loci in Cyclobalanopsis glauca (Fagaceae), an evergreen broadleaved monoecious
      tree, to provide tools for analyzing parentage and mating system. METHODS AND
      RESULTS: Thirteen polymorphic microsatellite markers were developed and tested in
      three C. glauca populations. The number of alleles per locus varied from two to
      22. The observed and expected heterozygosities within populations were 0.000
      0.967 and 0.033-0.949, respectively. CONCLUSIONS: These polymorphic primers
      showed high levels of polymorphism within tested populations, and can be used in
      parentage analysis and mating system estimation of C. glauca.

PMID- 22358046
TI  - Development of nuclear microsatellite markers for the fonio, Digitaria exilis
      (Poaceae), an understudied West African cereal.
AB  - PREMISE OF THE STUDY: We developed nuclear microsatellite primers to explore the
      genetic diversity, population genetic structure, and evolutionary history of the
      fonio (Digitaria exilis), an understudied cereal cultivated in West Africa.
      METHODS AND RESULTS: We used a microsatellite-enriched library approach to
      isolate and characterize 38 nuclear primer pairs (31 di-, five tri-, and two
      tetranucleotide repeats), of which 21 were polymorphic and exhibited a clear
      pattern in 36 accessions from West Africa. The number of alleles per locus ranged
      from two to 22, with a mean of 4.71, and expected heterozygosity ranged from 0.03
      to 0.93. CONCLUSIONS: The developed set of 21 polymorphic SSR markers will
      provide tools for population and evolutionary genetics studies of the cultivated
      fonio.

PMID- 22358047
TI  - Cause for pause after a perioperative catastrophe: one, two, or three victims?

PMID- 22358048
TI  - Blood pressure during cardiopulmonary bypass: how low is too low?

PMID- 22358049
TI  - Role of cardiac reflexes in the control of heart rate: what does the
      anesthesiologist need to know?

PMID- 22358050
TI  - A matter of conscience: a call to action for system improvements involving
      epidural and spinal catheters.

PMID- 22358051
TI  - International Anesthesia Research Society Annual Meeting: then & now.

PMID- 22358052
TI  - Anesthesia dogmas and shibboleths: barriers to patient safety?

PMID- 22358053
TI  - Chronic kidney disease and postoperative morbidity associated with renal
      dysfunction after elective orthopedic surgery.

PMID- 22358054
TI  - Novel method to prevent the inadvertent retention of throat pack.

PMID- 22358055
TI  - A simple alternative method to confirm lung separation.

PMID- 22358056
TI  - Carbon dioxide capture by aminoalkyl imidazolium-based ionic liquid: a
      computational investigation.
AB  - Efficient technologies/processes for CO(2) capture are greatly desired, and ionic
      liquids are recognized as promising materials for this purpose. However, the
      mechanisms for selectively capturing CO(2) by ionic liquids are unclear. In this
      study, the interactions between CO(2) and 1-n-amino-alkyl-3-methyl-imidazolium
      tetrafluoroborate, an amino imidazolium ionic liquid (AIIL), in its CO(2)
      capturing process, are elucidated with both quantum chemistry and molecular
      dynamics approaches on the molecular level. The effects of the straight
      aminoalkyl chain length in imidazolium-based cations on CO(2) capture are
      explored, and thereby the factors governing CO(2) capture for this ionic liquid
      family, e.g., ionic liquid structure, charge distribution, intermolecular
      interactions, thermodynamic properties and absorption kinetics, are analyzed.
      Molecular dynamics simulations are used to study the diffusion of the involved
      compounds and liquid structures of the CO(2)-AIIL systems. The results show that
      the amino-alkyl chain length plays an important role in governing the absorption
      properties of AIILs, including the free energies of absorption, equilibrium
      constants, desorption temperature, absorption rate constants, diffusion
      coefficients, and organization of CO(2) around cations and anions. This study
      provides useful information about rational design of ionic liquids for efficient
      CO(2) capture.

PMID- 22358057
TI  - Increased expression of Cxcr3 and its ligands, Cxcl9 and Cxcl10, during the
      development of alopecia areata in the mouse.

PMID- 22358059
TI  - miR-196a downregulation increases the expression of type I and III collagens in
      keloid fibroblasts.
AB  - Keloids are a fibroproliferative disease due to abnormal wound healing process
      after skin injury. They are characterized by overproduction of extracellular
      matrix (ECM) such as collagens. MicroRNAs (miRNAs) are noncoding small RNAs and
      negatively regulate protein expression. Several miRNAs that have critical roles
      in tissue fibrosis and ECM metabolism have been reported. However, regulation and
      function of miRNAs in keloid remain to be explored. The purpose of this study was
      to identify miRNAs involved in keloid pathogenesis. We performed miRNA microarray
      analysis to compare miRNA expression profiles between keloid-derived fibroblasts
      (KFs) and normal fibroblasts (NFs). In all, 7 upregulated and 20 downregulated
      miRNAs were identified. Among these, we focused on miR-196a, which showed the
      highest fold change. Overexpression or knockdown of miR-196a led to a decreased
      or increased level of secreted type I/III collagens, respectively. Reporter
      analysis showed direct binding of miR-196a to the 3' untranslated region (UTR) of
      COL1A1 and COL3A1. In conclusion, we demonstrate for the first time that miRNA
      expression profile is altered in KFs compared with NFs. Downregulation of miR
      196a may be one of the mechanisms by which collagens are highly deposited in
      keloid tissues. Our findings suggest that miR-196a could be a new therapeutic
      target for keloid lesions.

PMID- 22358058
TI  - gammadelta T cells augment rejection of skin grafts by enhancing cross-priming of
      CD8 T cells to skin-derived antigen.
AB  - Gamma delta T cells (gammadelta T cells) possess innate-like properties and are
      proposed to bridge the gap between innate and adaptive immunity. In this study,
      we explored the role of gammadelta T cells in cutaneous immunity using a skin
      transplantation model. Following engraftment of skin expressing cell-associated
      model antigen (Ag) (ovalbumin) in epithelial keratinocytes, skin-resident
      gammadelta T cells enhanced graft rejection. Although the effector function of
      CD8 T cells was intact in the absence of gammadelta T cells, cross-priming of CD8
      T cell to graft-derived Ag was impaired in the absence of gammadelta T cells. The
      reduced graft rejection and graft priming of gammadelta T-cell-deficient mice was
      evident in both acutely inflamed and well-healed grafting models. Furthermore,
      expression of the CD40 activation marker on migrating dendritic cells was lower
      in TCRdelta(-/-) mice compared with wild-type mice, regardless of the presence or
      absence of inflammation associated with grafting. These results indicate that
      gammadelta T cells enhance graft priming and consequently the likelihood of a
      successful immune outcome in the context of skin graft rejection, suggesting that
      gammadelta T cells may be an important component of immunity to epithelial
      cancers or infection.

PMID- 22358060
TI  - Nicastrin mutations in French families with hidradenitis suppurativa.

PMID- 22358061
TI  - Kallikrein-related peptidase 8-dependent skin wound healing is associated with
      upregulation of kallikrein-related peptidase 6 and PAR2.
AB  - Kallikrein-related peptidase 8 (KLK8) is believed to be involved in the
      maintenance of skin homeostasis and pathogenesis of inflammatory skin diseases.
      Although previous studies have shown that KLK8 is expressed around incisional
      wounds, the exact role of KLK8 in wound healing remains obscure. In the present
      study, we compared wound healing in wild-type (WT) and Klk8 gene-disrupted
      (kallikrein-related peptidase 8 knockout, Klk8(-/-)) mouse skin. Wound healing in
      Klk8(-/-) mice was hampered with defective keratinocyte proliferation,
      differentiation, and migration in the early stages of wound healing. Compared
      with the prominent induction of Klk6 and protease-activated receptor 2 (PAR2)
      messenger RNA, and protein in WT mice after wounding, a much lower increase was
      observed in Klk8(-/-) skin. After skin wounding in WT mice, increased Klk6 was
      detected from the upper stratum spinosum to the stratum corneum. Moreover, in WT
      mice, Klk6 protein was processed. PAR2 was diffusely expressed in the cytoplasm
      of the stratum spinosum at day 7 post wounding in WT mice. These results suggest
      that Klk8 is involved in the proliferation and migration of keratinocytes through
      the upregulation and activation of Klk6 in the early stages of wound healing, and
      possibly in keratinocyte differentiation associated with the upregulation and
      activation of PAR2 in the late stages of wound healing.

PMID- 22358062
TI  - Dickkopf 1 promotes regression of hair follicles.
AB  - Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved
      in male pattern baldness. As premature catagen onset is a key characteristic of
      male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a
      catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1
      (rhDKK-1) injection into the hypodermis of mice during anagen caused premature
      onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen
      transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final
      hair follicle length, whereas DKK-1 antibody led to an increase compared with
      control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most
      upregulated in follicular keratinocytes of late anagen in depilation-induced hair
      cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt
      mediated activation of beta-catenin signaling and induces the proapoptotic
      protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken
      together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen
      transition in the hair cycle by regulating the activity of follicular
      keratinocytes.

PMID- 22358063
TI  - Collapsed (kippah) hollow silica nanoparticles.
AB  - Novel collapsed kippah-like mesoporous silica nanoparticles were synthesized
      using an O/W microemulsion system. The oil (hexadecane) can escape from the core
      while water could not enter through the surfactant filled nanopores of the soft
      shell during synthesis.

PMID- 22358064
TI  - Is the radiological community within Europe ready for audit?

PMID- 22358065
TI  - Social behavior impairment in offspring exposed to maternal seizures in utero.
AB  - Human and animal models have demonstrated that maternal seizures in utero could
      be deleterious to the development of the offspring. This study focused on the
      social behavior of offspring exposed to seizures in utero. A pilocarpine model of
      temporal lobe epilepsy was induced in female Wistar rats that were mated after
      the first spontaneous seizure. Early after birth, pups from an epileptic mother
      were reared by a control mother. To evaluate the influence of the adoption
      process, two other groups were added: rat pups from control mothers cross
      fostered with other control mothers, and rat pups reared by their birth mother.
      Animals exposed to seizures in utero showed impaired social behavior with no
      signs of anxiety-like behavior. This study demonstrated that epileptic seizures
      during pregnancy could be harmful to brain development and may increase the risk
      of developing neurodevelopmental disorders. The mechanisms underlying the
      abnormalities of social behavior are not well understood, and further studies in
      this field are warranted.

PMID- 22358066
TI  - Chronic isolation stress compromises JNK/c-Jun signaling in rat brain.
AB  - The c-Jun NH2-terminal kinases (JNKs) are important stress-responsive kinases.
      They regulate cellular activities by sequential phosphorylation and activation
      through a mitogen-activated protein kinase cascade, whereas JNKs activation is
      altered in response to various stressors. In the present study, we used
      immunoblotting to assess the effect of 21 day of social isolation as the chronic
      stressor, either sole and in combination with 2 h of acute immobilization or cold
      (4 degrees C) stress on circulating corticosterone level and phosphorylation
      status of p46 (phospho-p46/total p46) and p54 (phospho-p54/total p54) JNK
      isoforms in the cytosolic and nuclear fraction of the prefrontal cortex and
      hippocampus of male Wistar rats. Also, the phosphorylation status of JNK nuclear
      down-stream target c-Jun (p-c-Jun/c-Jun) on Ser63 was examined. Both acute
      stressors with elevated CORT levels led to increased phosphorylation status of
      cytosolic p54 JNK isoforms but not p46 JNK isoforms only in the hippocampus and
      no change in phosphorylation status of c-jun in both brain regions. Chronic
      isolation with unaltered CORT level and reduced responsiveness to novel acute
      stressors, led to unchanged or reduced phosphorylation status of p46 and p54 JNK
      isoforms in both fractions and both brain regions, whereas the decrease of c-Jun
      phosphorylation status was found only in the prefrontal cortex. Our results
      suggest that compromised JNKs activation following chronic isolation may lead to
      interruption of JNK signaling, which could be related with neuropsychiatric
      disorders such as depression or long-lasting neuronal remodeling.

PMID- 22358067
TI  - Frequent extramedullary recurrence of isolated myeloid sarcoma in the long-term
      follow-up.

PMID- 22358068
TI  - Application of autologous stem cell transplantation in various adult and
      pediatric rheumatic diseases.
AB  - In the past 15 years, more than 1,500 patients worldwide have received a
      hematopoietic stem cell transplant, mostly autologous, as treatment for a severe
      autoimmune disease (AD). A recent retrospective analysis of 900 patients showed
      that the majority had multiple sclerosis, systemic sclerosis, systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis
      (JIA; n = 65) and idiopathic cytopenic purpura. An overall 85% 5-year survival
      and 43% progression-free survival was seen, with 100-day transplant-related
      mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Around 30% of
      patients in all disease subgroups had a complete response, despite full immune
      reconstitution. In many patients, morphological improvement was documented beyond
      any predicted known effects of intense immunosuppression alone. It is hoped that
      the results of three ongoing large prospective, randomized, controlled trials
      will allow modification of the protocols to reduce the high TRM, which relates to
      regimen intensity, age of patient, and comorbidity. Multipotent mesenchymal
      stromal cells (MSCs), including autologous MSCs, have recently been tested in
      various ADs, exploiting their immune-modulating properties and apparent low acute
      toxicity. Despite encouraging small phase I/II studies, no positive data from
      randomized, prospective studies are as yet available in the peer-reviewed
      literature.

PMID- 22358069
TI  - The actions of bismuth in the treatment of Helicobacter pylori infections: an
      update.
AB  - Helicobacter pylori causes various gastric diseases, such as gastritis, peptic
      ulcerations and gastric cancer. Bismuth-based triple or quadruple therapies have
      been commonly recommended for the treatment of H. pylori infections. Up to now,
      the molecular mechanisms by which bismuth inhibits the growth of H. pylori are
      far from clear. The present concise review intends to cover the most recent
      reports and discoveries in the field of the inhibitory mechanism of bismuth
      against H. pylori as well as the bacterial protective response to drug treatment,
      which will help us to further understand the molecular mechanisms underlying the
      actions of metal-based drugs and stimulate further development of effective anti
      bacterial drugs.

PMID- 22358071
TI  - Conceptions of healthy eating among ecological farmers in Parana, Southern
      Brazil.
AB  - OBJECTIVE: To describe ecological farmers' conceptions of healthy eating.
      METHODS: Study with a qualitative approach. In January and February 2007,
      supported by a guide, in-depth interviews were conducted with 11 women and one
      man who were living in an agricultural community in Rio Branco do Sul, Southern
      Brazil. The interviewees were selected randomly from among the 20 ecological
      farming families in this municipality. RESULTS: Three analysis categories were
      identified: "awareness of healthy eating"; "purchasing power" and "healthy land".
      The significance of healthy eating for the female farmers involved the idea that
      foods should be natural, without agricultural pesticides or manufactured chemical
      products. The daily routine should include abundant consumption of fruits, greens
      and other vegetables, in addition to the basic rice, beans and meat, and the
      composition of dishes should aim towards prevention of obesity and chronic
      degenerative diseases. Care regarding natural resources in order to ensure
      production of healthy foods, food safety, environmental sustainability and the
      future of life on the planet form part of the concept of healthy eating.
      CONCLUSIONS: Knowledge, self-criticism and discernment accompanied the
      conceptions of healthy eating.

PMID- 22358070
TI  - Regulation of pregnancy maintenance and fetal survival in mice by CD27(low)
      mature NK cells.
AB  - Uterine natural killer (NK) cells are pivotal for successful mammalian
      reproduction. However, insights on functionally distinct subpopulations of
      uterine NK cells are largely elusive. Furthermore, translation of findings from
      murine into human pregnancy has been overshadowed by the limited number of mutual
      phenotypic NK cell markers. We here provide evidence that a subset of murine
      mature NK (mNK) cells present at the feto-maternal interface, identified as
      CD27(low)DX5(+)CD3(neg), is pivotal in maintaining pregnancy. This mNK subset has
      low cytotoxic capacity, produces higher amounts of interferon (IFN)-gamma, and
      expresses functional homologs of human NK cell immunoglobulin-like receptors. We
      further show that bone marrow-derived CD27(low) mNK cells are selectively
      recruited to the uterus and ameliorate the rate of fetal loss when adoptively
      transferred into alymphoid RAG2(-/-)/gammac(-/-) mice. Additionally, expression
      of CD27 is down-modulated on mNK cells upon migration to the uterus. Hence, we
      propose the existence of a regulatory mNK cell subset, which is licensed toward
      successful pregnancy maintenance at the fetomaternal interface in mice. As
      CD27(low) NK cells are also present in human decidua, the CD27(low) NK subset may
      provide a tool to foster translational research in reproduction, aiming to
      improve pregnancy outcome in humans.

PMID- 22358072
TI  - Violence among female users of healthcare units: prevalence, perspective and
      conduct of managers and professionals.
AB  - OBJECTIVE: To estimate the prevalence of violence in women who are primary
      healthcare users and to verify if these situations were detected and how they
      were tackled by these services' professionals. METHODS: Descriptive, cross
      sectional study carried out with 14 municipal women's health coordinators, 2,379
      women who are users of primary healthcare units, 75 managers and 375
      professionals, in 15 municipalities of the State of Sao Paulo (Southeastern
      Brazil), between August 2008 and May 2009. Data were collected through structured
      questionnaires and a descriptive analysis was conducted. RESULTS: A specific
      protocol for assisting women in situations of violence was mentioned in five
      municipalities. The majority (83%) of the coordinators reported that situations
      of violence among female users were detected, although 74% said this was not
      routinely investigated, which was confirmed by 72.3% of the professionals. Among
      the women, 76.5% reported having experienced some type of violence throughout
      their lives, and 56.4% said that an intimate partner was the perpetrator of that
      violence; almost 30% reported at least one episode in the 12 months prior to the
      interview; 6.5% reported looking for help at a Primary Healthcare Unit.
      CONCLUSIONS: A relevant proportion of users experienced violence in their daily
      routine, mainly perpetrated by an intimate partner. Most of the women were
      neither identified nor approached in these services and did not receive help.
      Although health managers and professionals realized the magnitude of the problem,
      they did not consider that primary care was prepared to assist these women. The
      study showed that there is no intersectoral care network to assist women in
      situation of violence.

PMID- 22358073
TI  - A multifactorial approach to sickness absenteeism among nursing staff.
AB  - OBJECTIVE: To analyze factors associated with self-reported sickness absenteeism
      among nursing workers. METHODS: Cross-sectional study with 1,509 workers from
      three public hospitals in the city of Rio de Janeiro (Southeastern Brazil) in
      2006. Absenteeism was classified in three levels: no day, a few days (1-9 days)
      and many days (> 10 days), based on the answer to a question of the work ability
      index questionnaire. The logistic regression analysis considered a conceptual
      model based on distal (socioeconomic status), intermediate I (occupational
      characteristics), intermediate II (lifestyle characteristics), and proximal
      (diseases and health conditions) determinants. RESULTS: The frequencies of
      sickness absenteeism were 20.3% and 16.6% for a few days and many days,
      respectively. Those who reported more than one job, musculoskeletal diseases and
      rated their health as poor or regular had higher odds of absenteeism. Compared to
      nurses, nursing assistants were less likely to mention a few days, and
      technicians were more likely to have many days of absence. Higher odds of
      mentioning many days of absence were observed among public servants, compared to
      contract workers (OR = 3.12; 95%CI 1.86;5.22), and among married (OR = 1.73;
      95%CI 1.14;2.63) and separated, divorced and widowed individuals (OR = 2.06,
      95%CI 1.27;3.35), compared to singles. CONCLUSIONS: Different variables were
      associated with the two forms of absenteeism, which suggests its multiple and
      complex determination related to factors from different levels that cannot be
      exclusively explained by health problems.

PMID- 22358074
TI  - Psychiatric patients' return for HIV/STI test results in mental health centers.
AB  - OBJECTIVE: To assess individual and/or health service factors associated with
      patients returning for results of HIV or sexually transmitted infection (STI)
      tests in mental health centers. METHODS: Cross-sectional national multicenter
      study among 2,080 patients randomly selected from 26 Brazilian mental health
      centers in 2007. Multilevel logistic regression was used to assess the effect of
      individual (level 1) and mental health service characteristics (level 2) on
      receipt of test results. RESULTS: The rate of returning HIV/STI test results was
      79.6%. Among health service characteristics examined, only condom distribution
      was associated with receiving HIV/STI test results, whereas several individual
      characteristics were independently associated including living in the same city
      where treatment centers are; being single; not having heard of AIDS; and not
      having been previously HIV tested. CONCLUSIONS: It is urgent to expand HIV/STI
      testing in health services which provide care for patients with potentially
      increased vulnerability to these conditions, and to promote better integration
      between mental health and health services.

PMID- 22358075
TI  - Tracking of dietary patterns from childhood to adolescence.
AB  - OBJECTIVE: To review the scientific literature on the tracking of dietary
      patterns from childhood to adolescence. METHODS: A search of the MEDLINE/PubMed,
      Lilacs and SciELO databases was performed, using the following key words:
      "tracking", "dietary patterns" and "childhood/adolescence" and their respective
      synonyms. A total of 45 abstracts were found and, after the inclusion criteria
      were applied, 13 articles were included. The tracking of dietary patterns was
      assessed by three main statistical analyses: (Pearson or Spearman) correlation
      coefficients, kappa coefficient and probability analysis. RESULTS: The tracking
      of dietary patterns ranged from weak to moderate between the childhood-childhood
      and childhood-adolescence periods. During adolescence, there appears to be no
      tracking. CONCLUSIONS: Dietary patterns in childhood may continue until
      adolescence, although such patterns may be changed or discontinued throughout
      adolescence.

PMID- 22358076
TI  - Separation of CO2-CH4 mixtures in the mesoporous MIL-100(Cr) MOF: experimental
      and modelling approaches.
AB  - Carbon dioxide is the main undesirable compound present in raw natural gas and
      biogas. Physisorption based adsorption processes such as pressure swing
      adsorption (PSA) are one of the solutions to selectively adsorb CO(2) from CH(4).
      Some hybrid crystalline porous materials that belong to the family of metal
      organic frameworks (MOFs) show larger CO(2) adsorption capacity compared to the
      usual industrial adsorbents, such as zeolites and most activated carbons, which
      makes them potentially promising for such applications. However, their
      selectivity values have been most often determined using only single gas
      adsorption measurements combined with simple macroscopic thermodynamic models or
      by means of molecular simulations based on generic forcefields. The transfer of
      this systematic approach to all MOFs, whatever their complex physico-chemical
      features, needs to be considered with caution. In contrast, direct co-adsorption
      measurements collected on these new materials are still scarce. The aim of this
      study is to perform a complete analysis of the CO(2)-CH(4) co-adsorption in the
      mesoporous MIL-100(Cr) MOF (MIL stands for Materials from Institut Lavoisier) by
      means of a synergic combination of outstanding experimental and modelling tools.
      This solid has been chosen both for its fundamental interests, given its very
      large CO(2) adsorption capacities and its complexity with a combination of
      micropores and mesopores and the existence of unsaturated accessible metal sites.
      The predictions obtained by means of Grand Canonical Monte Carlo simulations
      based on generic forcefields as well as macroscopic thermodynamic (IAST, RAST)
      models will be compared to direct the co-adsorption experimental data
      (breakthrough curve and volumetric measurements).

PMID- 22358077
TI  - Verification of a depth-integrated sample arm as a means to reduce solids
      stratification bias in urban stormwater sampling.
AB  - A new water sample collection system was developed to improve representation of
      solids entrained in urban stormwater by integrating water-quality samples from
      the entire water column, rather than a single, fixed point. The depth-integrated
      sample arm (DISA) was better able to characterize suspended-sediment
      concentration and particle size distribution compared to fixed-point methods when
      tested in a controlled laboratory environment. Median suspended-sediment
      concentrations overestimated the actual concentration by 49 and 7% when sampling
      the water column at 3- and 4-points spaced vertically throughout the water
      column, respectively. Comparatively, sampling only at the bottom of the pipe, the
      fixed-point overestimated the actual concentration by 96%. The fixed-point
      sampler also showed a coarser particle size distribution compared to the DISA
      which was better able to reproduce the average distribution of particles in the
      water column over a range of hydraulic conditions. These results emphasize the
      need for a water sample collection system that integrates the entire water
      column, rather than a single, fixed point to properly characterize the
      concentration and distribution of particles entrained in stormwater pipe flow.

PMID- 22358078
TI  - Pharmacological activity of salvinorin A, the major component of Salvia
      divinorum.
AB  - The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the
      Sage family that has been historically used for divination and shamanism by the
      Mazatecs. Today, S. divinorum has become increasingly popular as a recreational
      drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A,
      the major active component of S. divinorum, is responsible for the hallucinogenic
      effect of this plant. Here, we described the behavioral effects of salvinorin A
      in animals including the addictive, antinociception and antidepressant properties
      of the drug. The present paper also demonstrates the not well recognized (or
      unclear) mechanisms of action of salvinorin A. The last part of the paper
      presents information about the legal status of S. divinorum and its derivatives.
      Taking into account the increasing popularity and consumption of salvinorin A and
      S. divinorum today, it is important to collect all data on the pharmacological
      profile of this plant and its products.

PMID- 22358079
TI  - Role of serotonin 5-HT1B receptors in psychostimulant addiction.
AB  - Psychostimulant (cocaine, amphetamine and its derivatives)  addiction is an
      important health problem with implications in social and economic life. Although
      mesocorticolimbic dopamine system plays a crucial role in the mechanism
      responsible for the rewarding effects of these drugs, recent data also show
      involvement of the brain serotonin (5-HT) system. In the present review we
      discuss the role of 5-HT(1B) receptors in the psychostimulant addiction on the
      base of the effects of 5-HT(1B) receptor ligands on the behavioral effects of the
      psychostimulants in experimental models (sensitization, intracranial self
      stimulation, conditioned place preference, self-administration and
      extinction/reinstatement model) used to assess their addictive properties.
      Moreover, the effect of long-term treatment with psychostimulants on 5-HT(1B)
      receptors is also discussed.

PMID- 22358080
TI  - Neurogenesis in the epileptic brain: a brief overview from temporal lobe
      epilepsy.
AB  - Dentate granule cell neurogenesis persists throughout life in the hippocampus of
      mammals. Alterations in this process occur in many neurological diseases,
      including epilepsy. Among the different types of epilepsy, the most frequent is
      temporal lobe epilepsy (TLE). Therefore, a number of laboratory studies use
      animal models of TLE to observe the fate of neuronal cells after seizures.
      Hippocampal neurogenesis is very sensitive to physiological and pathological
      stimuli. Seizures, as pathological stimuli, alter both the extent and the pattern
      of neurogenesis, which is associated with cognitive function. Various alterations
      in neurogenesis are observed depending on the amount of time that has elapsed
      after the seizures. In acute seizures, neurogenesis generally increases, whereas
      in chronic epilepsy, neurogenesis decreases. Moreover, several methods currently
      used for the treatment of brain disorders such as TLE can also have significant
      impacts on cognitive functions. This review is focused on the recent findings
      regarding neurogenesis in animal models of TLE.

PMID- 22358081
TI  - Kynurenic acid and kynurenine aminotransferases in retinal aging and
      neurodegeneration.
AB  - The kynurenine aminotransferases (KATs) KAT I and KAT II are pivotal to the
      synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor
      antagonist and neuroprotectant. KAT I and II have been found in avian, rodent,
      and human retina. Expression of KAT I in Muller cell endfeet and KAT II in
      retinal ganglion cells has been documented. Developmental changes in KAT
      expression and KYNA concentration in the avian and rodent retina have also been
      found. Studies of retinal neurodegeneration have shown alterations in KYNA
      synthesis in the retina in response to retinal ganglion cell loss. In DBA/2J
      mice, a model of ocular hypertension, an age-dependent decrease of retinal KYNA
      and KATs was found. In the corpora amylacea in the human retina intensive KAT I
      and II immunoreactivity was demonstrated. In summary, these findings point to the
      potential involvement of KYNA in the mechanisms of retinal aging and
      neurodegeneration.

PMID- 22358082
TI  - Ezetimibe--a new approach in hypercholesterolemia management.
AB  - Ezetimibe is the first agent used in hypercholesterolemia treatment known to
      lower intestinal cholesterol uptake that is able to inhibit NPC1L1 transport
      proteins in the brush boarder of enterocytes and macrophages. Furthermore, it
      demonstrates anti-inflammatory and immunomodulatory properties and influences the
      expression of certain antigens. The drug is rapidly absorbed from the
      gastrointestinal tract and is then glucuronidated to form the active metabolite.
      It also undergoes extensive enterohepatic circulation. Various genetic
      polymorphisms seem to influence the pharmacokinetics of ezetimibe with different
      effects. The drug also presents a complex impact on cytochrome P450 enzymes, as
      it is a metabolism-dependent inhibitor of CYP3A4. Ezetimibe does not demonstrate
      any clinically significant interactions with statins, fibrates, mipomersen
      sodium, levothyroxine or lopinavir. However, its effect in conjunction with
      cyclosporine is not neutral. The use of this cholesterol absorption inhibitor has
      been shown to be safe and effective among patients after cardiac, renal and liver
      transplants, as well as in HIV patients.

PMID- 22358083
TI  - Effects of the noradrenergic neurotoxin DSP-4 on the expression of alpha1
      adrenoceptor subtypes after antidepressant treatment.
AB  - We have previously reported that chronic imipramine and electroconvulsive
      treatments increase the alpha(1A)-adrenoceptor (but not the alpha(1B) subtype)
      mRNA level and the receptor density in the rat cerebral cortex. Furthermore, we
      have also shown that chronic treatment with citalopram does not affect the
      expression of either the alpha(1A)- or the alpha(1B)-adrenoceptor, indicating
      that the previously observed up-regulation of alpha(1A)-adrenoceptor may depend
      on the noradrenergic component of the pharmacological mechanism of action of
      these antidepressants. Here, we report that previous noradrenergic depletion with
      DSP-4 (50 mg/kg) (a neurotoxin selective for the noradrenergic nerve terminals)
      significantly attenuated the increase of alpha(1A)-adrenoceptor mRNA induced by a
      14-day treatment with imipramine (IMI, 20 mg/kg, ip) and abolished the effect of
      electroconvulsive shock (ECS, 150 mA, 0.5 s) in the prefrontal cortex of the rat
      brain. The changes in the receptor protein expression (as reflected by its
      density) that were induced by IMI and ECS treatments were differently modulated
      by DSP-4 lesioning, and only the ECS-induced increase in alpha(1A)-adrenoceptor
      level was abolished. This study provides further evidence corroborating our
      initial hypothesis that the noradrenergic component of the action of
      antidepressant agents plays an essential role in the modulation of alpha(1A)
      adrenoceptor in the rat cerebral cortex.

PMID- 22358084
TI  - GET73 modulates rat hippocampal glutamate transmission: evidence for a functional
      interaction with mGluR5.
AB  - In the present study, the effects of the gamma-hydroxybutyrate (GHB) analog GET73
      on hippocampal glutamate transmission have been evaluated by an approach
      combining in vivo microdialysis with the in vitro evaluation of tissue slices.
      The microdialysis results indicated that local perfusion (60 min) with 10 nM -
      1mM GET73 increased extracellular glutamate levels in the CA1 region of the
      hippocampus of freely moving rats in a concentration dependent manner. In tissue
      slices from the rat hippocampus, GET73 (1 MUM - 10 MUM) did not affect L
      [(3)H]glutamate uptake, whereas treatment with 1 MUM GET73 significantly
      increased K(+)-evoked, but not spontaneous, glutamate efflux. The GHB analog did
      not affect the increase in glutamate efflux induced by 100 MUM and 300 MUM NMDA.
      In contrast, 500 nM GET73, a concentration at which it is ineffective alone,
      partially but significantly counteracted the increase in K(+)-evoked glutamate
      efflux induced by 100 MUM CHPG, an mGluR5 agonist. When 500 nM GET73 was
      coperfused with 100 MUM MPEP, it amplified the decrease in K(+)-evoked glutamate
      efflux induced by the mGluR5 antagonist. Interestingly, the increase in K(+)
      evoked glutamate efflux induced by 1 MUM GET73 was counteracted by coperfusion
      with a low (10 MUM) concentration of MPEP, which by itself is ineffective.
      Finally, 500 nM GET73 did not affect the reduction of K(+)-evoked glutamate
      efflux induced by the mGluR2/3 agonist LY379268. These findings demonstrate that
      the GHB analog GET73 significantly affects glutamate transmission in the
      hippocampus, and its profile of action differs from that of its parent compound.

PMID- 22358085
TI  - Memory-related effects of cholinergic receptor ligands in mice as measured by the
      elevated plus maze test.
AB  - The purpose of our experiments was to examine the influence of cholinergic
      receptor ligands on memory-related behavior in mice using the elevated plus maze
      (EPM) test. The EPM test allows the exploration of different memory processes
      (acquisition and consolidation), depending on the time of drug treatment. The
      time necessary for mice to move from the opened arm to the enclosed arm (i.e.,
      transfer latency, TL) was used as an index of memory. Our findings reveal that
      for both the processes of acquisition and consolidation, treatment with nicotine
      (0.035 or 0.175 mg/kg, free base, sc) shortened TL on the second day of the
      experiments (TL2), thus improving memory processes. Treatment with scopolamine
      (0.3 or 1.0 mg/kg, ip) significantly increased TL2 values, thus impairing
      cognitive processes. Moreover, we found that treatment with nicotine, at the non
      effective doses used during testing, prevented scopolamine-induced memory
      impairment by inducing a decrease in TL2 values. Next, we evaluated the influence
      of bupropion (10 or 20 mg/kg, ip), a drug currently used for smoking cessation in
      humans, on memory-related behavior induced by treatment with nicotine and
      scopolamine. An acute injection of bupropion (10 or 20 mg/kg) prior to injection
      with either nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg) significantly
      prevented nicotine-induced memory improvement or scopolamine-induced memory
      impairment. Bupropion treatment can diminish the rewarding (dependence-producing)
      effects of nicotine and also the cognitive effects that are related to addiction.
      Our studies further indicate the great involvement of the cholinergic system in
      memory processes and the potential for the development of more effective
      pharmacotherapies for memory impairment-like human disorders in which the
      cholinergic pathways have been implicated.

PMID- 22358086
TI  - Partial lesion of the dopaminergic innervation of the ventral striatum induces
      "depressive-like" behavior of rats.
AB  - Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may
      precede appearance of its motor symptoms by several years. Pathomechanisms
      underlying PD have been suggested to be responsible for the PD-related
      depression. The aim of the study was to examine the influence of a partial lesion
      of striatal dopaminergic terminals on the "depressive-like" behavior of rats in
      the forced swimming test (FS). 6-Hydroxydopamine (6-OHDA) was injected
      bilaterally into the ventro-lateral region of the caudate-putamen (CP) (3.75
      MUg/2.5 MUl/side). The locomotor activity and behavior of rats in the FS were
      measured 2 and 4 weeks after the operation. The lesion extent was analyzed by
      biochemical and immunohistochemical methods. Two weeks after the operation, the 6
      OHDA-treated rats displayed a prolonged immobility in the FS. This effect
      disappeared after 4 weeks. The locomotor activity was not influenced by 6-OHDA.
      Levels of dopamine, DOPAC and HVA were decreased in the nucleus accumbens (NAC) 2
      weeks after 6-OHDA but were not changed in the CP, frontal cortex (FCX) and
      substantia nigra (SN). No significant effect of 6-OHDA on tyrosine hydroxylase
      immunoreactivity in the CP and NAC were found. The present study indicates that a
      relatively small lesion of dopaminergic terminals in the ventral striatum, which
      does not produce any motor disturbances, may induce "depressive-like" symptoms.

PMID- 22358087
TI  - Effect of prior stress on interleukin-1beta and HPA axis responses to acute
      stress.
AB  - Interleukin-1beta (IL-1beta) level is modulated during multiple stress reactions
      both in brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis
      regulation and peripheral systems. Multiple distinct stressors induce different
      IL-1beta and HPA axis responses. The purpose of the present study was to
      determine if the effect of prior repeated restraint stress on IL-1beta levels in
      prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on
      alterations induced in HPA axis responses. Experiments were performed on male
      Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days.
      Twenty four hours after the last stress period rats were restrained for 10 min
      and decapitated at 0, 1, 2 or 3 h after cessation of stress. Control rats were
      injected ip with saline and some of experimental groups with IL-1beta receptor
      antagonist (IL-1ra). After rapid decapitation, trunk blood was collected and
      prefrontal cortex, hippocampus and hypothalamus were excised and frozen.
      Interleukin-1beta, adrenocorticotropic hormone (ACTH) and corticosterone (CORT)
      levels were determined in plasma using commercially available kits and IL-1beta
      levels in brain structures samples were analyzed by western blot procedure.
      Repeated restraint for 3 days alone did not alter resting plasma levels of IL
      1beta, and moderately augmented plasma ACTH and CORT levels and IL-1beta content
      in brain structures 24 h after the last restraint. IL-1beta antagonist abolished
      the increase in plasma levels of IL-1beta, ACTH and CORT as well as IL-1beta in
      brain structures in response to repeated stress and also reduced these changes
      induced by 10 min stress. This suggests the selectivity of IL-1beta receptors in
      central and peripheral mechanisms modulating the stress-induced HPA axis
      responses. These results indicate that repeated stress markedly increases IL
      1beta production in brain structures involved in HPA axis regulation. The present
      results support the role of brain and peripheral IL-1beta in adaptation of HPA
      response during prolonged stress.

PMID- 22358088
TI  - Imipramine counteracts corticosterone-induced enhancement of glutamatergic
      transmission and impairment of long-term potentiation in the rat frontal cortex.
AB  - The effects of corticosterone administration lasting for 7 and 21 days were
      studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of
      the hormone. In slices originating from corticosterone-treated animals, the
      amplitude of extracellular field potentials recorded in cortical layer II/III was
      increased. Corticosterone administration also resulted in an increase of the mean
      frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic
      currents (sEPSCs) in layer II/III pyramidal neurons. These effects were
      accompanied by a reduced magnitude of long-term potentiation (LTP) of field
      potentials. In a separate set of experiments, rats were treated with
      corticosterone for 21 days and additionally with a tricyclic antidepressant,
      imipramine, beginning on the eighth day of corticosterone administration. In this
      experimental group, the amplitude of field potentials, the mean frequency of
      sEPSCs and the magnitude of LTP were not different from the control, indicating
      that corticosterone-induced modifications of basal glutamatergic transmission and
      synaptic plasticity were reversed by the antidepressant.

PMID- 22358089
TI  - Investigations on gastroprotective effect of citalopram, an antidepressant drug
      against stress and pyloric ligation induced ulcers.
AB  - The present study investigates the gastroprotective effect of citalopram, an
      antidepressant drug. Gastroprotective activity of citalopram (5, 10 and 20 mg/kg,
      bid, po) was evaluated both by single and 14 days repeated pretreatment in the
      cold restraint stress (CRS) model and 14 days repeated pretreatment in pyloric
      ligation (PL) model. In addition to ulcer scoring and its histological
      assessment, levels of corticosterone, hexosamine, nitrite, PGE(2), lipid peroxide
      and microvascular permeability were also estimated. Mechanism underlying
      gastroprotective activity was further explored by investigating the involvement
      of nitric oxide (NO), sulfhydryl (SH) compounds, ATP-sensitive K(+) channels
      (K(ATP) channels) and prostaglandins (PGs). Results show that against CRS model,
      repeated pretreatment with citalopram exhibit a significant gastroprotective
      effect while single pretreatment was ineffective. In CRS model, citalopram
      repeated pretreatment, in contrast to its single pretreatment, attenuates the
      corticosterone level and also mitigates the stress-induced increase in nitrite
      level, lipid peroxidation and microvascular permeability. Additionally, the
      repeated pretreatment increases the hexosamine and PGE(2) level in CRS model.
      This gastroprotective effect of citalopram was found to be decreased with L-NAME,
      NEM, glibenclamide and indomethacin pretreatment. Thus, gastroprotective activity
      of citalopram appears to be mediated by endogenous NO, SH, PGs and K(ATP) channel
      opening. In contrast to CRS model, repeated pretreatment with citalopram was
      ineffective in reducing ulcer formation in PL model.

PMID- 22358090
TI  - Modification of local anesthetic-induced antinociception by fentanyl in rats.
AB  - In clinical practice, using the lowest doses of drugs for anesthesia or analgesia
      is the main goal. Opioid combinations with local anesthetics can be preferable
      for achieving adequate anesthesia or analgesia. The primary purpose of this study
      was to examine possible thermal antinociceptive effects of the opioid -fentanyl
      and the amide local anesthetics levobupivacaine and lidocaine when locally
      administered alone or in combination. The paw withdrawal latencies to noxious
      thermal stimuli in rats were measured to assess the antinociceptive actions of
      drugs after subcutaneous intraplantar injection into the hind paw. All drugs
      examined in this study produced dose- and time-dependent increases in the paw
      withdrawal latencies. Fentanyl is approximately 125 and 500 times more potent
      than levobupivacaine and lidocaine, respectively. At the same dose, the
      antinociceptive potency of levobupivacaine was 3.6-fold higher than that of
      lidocaine. Co-injection of the lowest doses of levobupivacaine and lidocaine
      dramatically increased the paw withdrawal latency. However, in the presence of
      fentanyl, the effects of levobupivacaine and lidocaine were different. Although
      co-injection of levobupivacaine with fentanyl both enhanced and prolonged
      antinociceptive action, the lidocaine-fentanyl combination did not significantly
      change the paw withdrawal latency. These results suggest that intraplantar co
      administration of fentanyl with levobupivacaine, but not lidocaine, may provide
      more effective antinociception without increasing the dose requirements.

PMID- 22358091
TI  - Paracetamol treatment increases telomerase activity in rat embryonic liver cells.
AB  - Although paracetamol is known to have a damaging effect, this pharmaceutical is
      widely applied to pregnant and lactating women. Despite substantial progress in
      our understanding of its hepatotoxicity, some mechanisms, particularly of its
      embryonal and developmental toxicity, are still unknown. Thus, cell culture
      assays that investigate its toxicity are of particular interest. We assessed the
      effects of acute paracetamol treatment on cell viability (LDH assay, MTT assay),
      glutathione content (GSH assay), metabolic status (albumin and urea assays) and
      telomerase activity using rat embryonic liver cells (RLC-18 cells). Incubation
      with low (6 mmol/l) and high (15 mmol/l) concentrations of toxin for 24 h leads
      to 20% and 50% cytotoxicity, respectively. Paracetamol exerted its toxicity in a
      similar pathway (depletion of GSH stores) as in adult liver cells, producing
      damage at the cellular level. Interestingly, paracetamol treatment significantly
      enhanced telomerase activity. Mechanisms involved in paracetamol-induced
      inhibition of cell senescence should be further elucidated. Telomerase activity
      in RLC-18 cells offers unique opportunities for examining basic biologic
      mechanisms. Our findings should encourage further studies to investigate a link
      between telomerase activity and toxicity, implying a role of impaired telomerase
      activity in human pathology.

PMID- 22358092
TI  - Novel I1-imidazoline S43126 enhance insulin action in PC12 cells.
AB  - The I(1)-imidazoline receptor is a novel target for drug development for
      hypertension and insulin resistance, major disorders associated with type 2
      diabetes. In the present study, we examined the effects of a novel imidazoline
      agonist S43126, on phosphorylation of protein kinase B (PKB/Akt) and
      extracellular signal-regulated kinase (ERK1/2) in PC12 cells. We further examined
      the effects of S43126 on insulin stimulated PKB and ERK phosphorylation. PC12
      cells were treated with varying doses of S43126 (10(-10) to 10(-6) M) or insulin
      (10(-10) to 10(-6) M) or combination treatment with insulin (10(-6) M) and
      varying doses of S43126 (10(-6) - 10(-11) M) for 10 min. Western blot analysis of
      treated samples showed that S43126 increased both ERK1/2 and PKB phosphorylation
      by 5 fold. Combination treatment with insulin (10(-6) M) and varying doses of
      S43126 (10(-6) - 10(-11) M) enhanced phosphorylation of PKB and ERK1/2 above the
      level of insulin alone, in a dose and time dependent manner. Treatment with siRNA
      against Nischarin (mouse homologue of I(1)-imidazoline receptor) reduced the
      phosphorylation of both ERK and PKB following combination treatments. These
      results indicate that S43126 has the potential to augment insulin action and
      should be further studied as a possible candidate drug for the treatment of
      insulin resistance states.

PMID- 22358093
TI  - Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT3
      receptor-mediated Bezold-Jarisch reflex in rats.
AB  - The Bezold-Jarisch reflex is characterized by a sudden bradycardia associated
      with hypotension induced by the activation of the vanilloid TRPV1 and serotonin 5
      HT(3) receptors. This reflex is associated with several health conditions,
      including myocardial infarction. The aim of the present study was to elucidate
      the influence of acute experimental myocardial ischemia on the reflex bradycardia
      induced by anandamide and phenylbiguanide, agonists of the TRPV1 and 5-HT(3)
      receptors, respectively. In urethane-anesthetized rats, the rapid iv injection of
      anandamide (0.6 MUmol/kg) or phenylbiguanide (0.03 MUmol/kg) decreased heart rate
      (HR) by about 7-10% of the basal values. Myocardial ischemia (MI) was induced by
      ligation of the left anterior coronary artery. The agonists were injected 5 min
      before MI (S(1)) and 10, 20 and 30 min thereafter (S(2)-S(4)). MI potentiated the
      anandamide-induced reflex bradycardia by approximately 105% at S(2) and 70% at
      S(3) but had no effect at S(4). This amplificatory effect of MI was virtually
      abolished by the TRPV1 receptor antagonist capsazepine (1 MUmol/kg) and was not
      modified by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 MUmol/kg).
      MI also amplified the reflex bradycardia elicited by phenylbiguanide by
      approximately 110, 60 and 90% (S(2), S(3) and S(4), respectively), and this
      effect was sensitive to the 5-HT(3) receptor antagonist ondansetron (3 MUmol/kg).
      In conclusion, our results suggest that acute myocardial ischemia augments the
      Bezold-Jarisch reflex induced via activation of TRPV1 and 5-HT(3) receptors
      located on sensory vagal nerves in the heart.

PMID- 22358094
TI  - Effects of two isomers of DDT and their metabolite DDE on CYP1A1 and AhR function
      in human placental cells.
AB  - The aim of this study was to investigate the actions of two isomers of DDT (p,p'
      DDT, o,p'-DDT) and DDE (p,p'-DDE, o,p'-DDE) on the human placenta. We studied the
      effects of DDT and its metabolite DDE on CYP1A1 activity and on CYP1A1 and aryl
      hydrocarbon receptor (AhR) protein expression in placental cells. We used
      explants from third-trimester human placental tissue and JEG-3 cells, which are
      first-trimester human placenta cells. The main finding of this study was that the
      activity of CYP1A1 in the human placenta, measured in terms of ethoxyresorufin-O
      deethylase (EROD) activity, was suppressed by treatment of 1, 10, and 100 ng/ml
      p,p'-DDT, o,p'-DDT, p,p'-DDE and o,p'-DDE. Immunoblot analyses indicated that
      both isomers of DDT and DDE inhibited the expression of CYP1A1 most effectively
      at 48 h and/or 72 h after the treatment. Because CYP1A1 activity is mediated by
      AhR, we evaluated the expression of AhR in placental tissue exposed to DDT and
      DDE for 1 h to 72 h. Our data showed that DDT and DDE gradually decreased the
      level of AhR protein, starting at 3 h or 24 h after the start of the experiment.
      Our results strongly support the involvement of the AhR/CYP1A1 signaling pathway
      in the mechanism of action of DDT and DDE in the human placenta.

PMID- 22358095
TI  - Cytoprotective effects of CSTMP, a novel stilbene derivative, against H2O2
      induced oxidative stress in human endothelial cells.
AB  - A novel stilbene derivative, (E)-2-(2-chlorostyryl)-3,5,6-trimethylpyrazine
      (CSTMP), was designed and synthesized based on the pharmacophores of
      tetramethylpyrazine (TMP) and resveratrol (RES). In the present study, we
      investigated the protective effects of CSTMP on vascular endothelial cells under
      oxidative stress and elucidated its molecular mechanisms. The radical scavenging
      activity of CSTMP was assessed by the DPPH test. Human Umbilical Vein Endothelial
      Cells (HUVECs) were exposed to 150 MUM hydrogen peroxide (H(2)O(2)) for 12 h,
      resulting in a decrease of cell viability assessed by the MTT assay and an
      increase of apoptotic cells assessed by the nuclear staining assay and flow
      cytometry. The activities of lactate dehydrogenase (LDH), superoxide dismutase
      (SOD) and nitric oxide synthase (NOS) and the contents of malondialdehyde (MDA),
      reduced glutathione (GSH) and nitric oxide (NO) in cells were determined by
      commercial kits. The expression levels of pro-apoptotic factor caspase-3 and anti
      apoptotic signal ERK1/2 were detected by western blot. The results showed that
      CSTMP had a moderate anti-oxidative effect against the DPPH test, which was less
      than RES. Co-incubation with CSTMP increased the cell viability, markedly reduced
      the LDH leakage from the cells and decreased the lipid peroxidation. These
      effects of CSTMP were accompanied by increasing activity of the endogenous
      antioxidant enzyme SOD, the level of GSH, the production of NO and cNOS activity.
      Moreover, CSTMP showed stronger effects on the inhibition of apoptosis, caspase-3
      expression, and the activation of phosphorylated ERK1/2 compared to RES.
      Furthermore, CSTMP could inhibit the expression of phospho-JNK and phospho-p38
      induced by H(2)O(2). These results suggest that CSTMP prevents H(2)O(2)-induced
      cell injury through anti-oxidation and anti-apoptosis via the MAPK and caspase-3
      pathways.

PMID- 22358096
TI  - Effects of bestatin on phagocytic cells in cyclophosphamide-treated mice.
AB  - The low-molecular weight dipeptide bestatin is a potent inhibitor of
      aminopeptidase N and has been demonstrated to have antitumor and immunomodulatory
      effects. The effects of bestatin on interleukin (IL)-1beta synthesis and release
      by peritoneal macrophages stimulated in vitro with lipopolysaccharide (LPS) from
      E. coli, the phagocytic and oxidative burst activity from peripheral blood
      monocytes and granulocytes and the number of blood leukocytes and blood picture
      in cyclophosphamide-treated mice were tested. Bestatin at doses of 1 and 0.1
      mg/kg was injected into cyclophosphamide-treated mice ip five times on
      alternating days or ten times at 24 h intervals. The first dose of bestatin was
      administered 24 h after a single injection of cyclophosphamide at a dose of 350
      mg/kg. It was found that bestatin administered at doses of 1 and 0.1 mg/kg five
      times on alternating days increased the synthesis and release of IL-1beta by
      resident peritoneal murine macrophages stimulated in vitro with LPS in
      cyclophosphamide-treated mice. The immunocorrecting action of bestatin on the
      picture of peripheral blood in cyclophosphamide-treated mice was primarily
      observed with young forms of neutrophilic granulocytes. The changes were observed
      irrespective of the dosage and the number of subsequent doses applied. Moreover,
      the administration of bestatin after pharmacological immunosuppression partially
      prevented the suppressive effects of cyclophosphamide on the oxidative burst
      activity of peripheral blood monocytes and stimulated the phagocytic activity of
      granulocytes.

PMID- 22358097
TI  - Effect of neuroleptics on cytochrome P450 2C11 (CYP2C11) in rat liver.
AB  - The aim of the present study was to investigate the influence of classic and
      atypical neuroleptics on the activity of cytochrome P450 2C11 (CYP2C11), measured
      as a rate of testosterone 2alpha- and 16alpha-hydroxylation. The reaction was
      studied in control liver microsomes in the presence of neuroleptics, as well as
      in the microsomes of rats treated intraperitoneally (ip) with pharmacological
      doses of the drugs (promazine, levomepromazine, thioridazine and perazine 10
      mg/kg; chlorpromazine 3 mg/kg; haloperidol 0.3 mg/kg; risperidone 0.1 mg/kg;
      sertindole 0.05 mg/kg) for one day or two weeks (twice a day), in the absence of
      the neuroleptics in vitro. The investigated neuroleptics added to control liver
      microsomes produced some inhibitory effects on CYP2C11 activity, which were
      moderate (thioridazine: K(i) = 55), modest (sertindole and perazine: K(i) = 76
      and 94 MUM, respectively) or week (promazine, levomepromazine, haloperidol and
      chlorpromazine: K(i) = 285, 280, 223 and 157 MUM, respectively). Risperidone had
      the weakest inhibitory effect on the CYP2C11 activity (K(i) = 641 MUM). One-day
      exposure of rats to the neuroleptics did not significantly change the activity of
      CYP2C11 in liver microsomes. Of the neuroleptics studied, only chronic treatment
      with levomepromazine, perazine and thioridazine diminished CYP2C11 activity;
      those effects were positively correlated with the observed decreases in the
      protein level of the enzyme. The in vivo inhibition of CYP2C11 by chronic
      treatment with the three phenothiazines suggests their influence on the enzyme
      regulation. A possible mechanism of CYP2C11 regulation by the neuroleptics and
      its pharmacological significance are discussed.

PMID- 22358098
TI  - Oleanolic acid derivative methyl 3,11-dioxoolean-12-en-28-olate targets multidrug
      resistance related to ABCB1.
AB  - Multidrug resistance (MDR) in leukemia patients is a great  incentive to the
      development of new drugs. In a search for potential multidrug resistance
      modulators we tested a group of oleanolic acid (OA) analogues modified at C-3, C
      11, C-12 and C-28 using an experimental model consisting of three human acute
      lymphoblastic leukemia cell lines (CCRF-CEM and the multidrug resistant sublines
      CCRF-VCR1000 and CCRF-ADR5000). The most effective compound, methyl 3,11
      dioxoolean-12-en-28-olate (DIOXOL) was more potent in cell viability inhibition
      than its precursor - OA, and showed similar or even higher activity in the drug
      resistant than in the wild-type cells. Resistance factor (RF) values obtained for
      CCRF-VCR1000 and CCRF-ADR-5000 cells using MTT assay were 0.7 and 0.8 (24 h of
      treatment) and after 72 h of treatment 0.9 and 1.1, respectively. Moreover, 5 MUM
      DIOXOL significantly reduced the expression of the ABCB1 gene in MDR cells by
      around 30%, and also decreased the level of P-gp protein. Compared to untreated
      control cells, DIOXOL treatment resulted in a significant P-gp decrease (30% in
      CCRF-ADR5000 and 50% in CCRF-VCR1000), that was detected by western blot and
      confirmed by flow cytometry analysis. Moreover, DIOXOL (at 10 MUM) significantly
      inhibited P-gp transport function by more than twofold comparing to control,
      untreated cells that was demonstrated using rhodamine 123-based functional test.
      The compound exhibited synergistic activity with ABCB1 substrate - adriamycin in
      CCRF-VCR1000 cells, indicating partial but significant MDR reversing ability.

PMID- 22358099
TI  - Comparison of the pharmacokinetics of paracetamol from two generic products in
      patients after total gastric resection.
AB  - Gastrectomy leads to pathophysiological changes within the alimentary tract,
      which may affect drug absorption and pharmacokinetic parameters (PK). The need to
      apply orally administered analgesics in this group of patients is often related
      with alternative application of currently available generic products. Thus, from
      the clinical point of view it is necessary to evaluate the PK of these drugs to
      confirm their equivalence. The aim of the study was therefore an analysis of the
      pharmacokinetics of paracetamol from two generic products in patients after total
      gastric resection. The research was carried out on two groups of patients after
      gastrectomy with Roux-en-Y reconstruction (n = 30; mean [SD] age, 63.0 [11.5]
      years; weight, 67.6 [13.7] kg; and height, 166.4 [9.1] cm). The patients received
      paracetamol in a single orally administered dose of 1,000 mg. Blood samples were
      collected within 6 h of drug administration. The concentration of paracetamol and
      paracetamol glucuronide in the blood plasma was marked by means of a validated
      high-pressure liquid chromatography with ultraviolet detection (HPLC-UV). The
      main PK for paracetamol in group 1 (n = 17) and 2 (n = 13) were as follows:
      C(max), 9.46 (3.66) and 12.79 (5.32) MUg/ml, respectively (p = 0.0517); AUMC(0
      t), 77.64 (30.37) and 51.01 (15.76) MUg h(2)/ml (p = 0.0046); AUC(0-inf), 41.61
      (23.52) and 30.28 (9.74) MUg h/ml (p = 0.0862); t(max), 1.68 (0.63) and 0.50
      (0.25) h (p < 0001). The obtained C(max) and AUC values in patients after
      gastrectomy were reduced in comparison with healthy subjects. Total gastrectomy
      therefore affected the pharmacokinetics of paracetamol administered in tablets.
      In our patients, we also observed significant differences between the PK of
      paracetamol and two generic preparations. These two drugs can thus be used
      interchangeably, but with caution.

PMID- 22358100
TI  - NMDA and AMPA receptors are involved in the antidepressant-like activity of
      tianeptine in the forced swim test in mice.
AB  - It is known that tianeptine exhibits antidepressant-like activity. Its influence
      on the glutamatergic system is also known, but the mechanisms involved in this
      activity remain to be established. The aim of this study was to investigate the
      involvement of the glutamate pathway in the antidepressant-like action of
      tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on
      tianeptine-induced activity in the forced swim test (FST) in mice. The
      antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly
      antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover,
      low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg,
      ip) administered together with low, ineffective doses of tianeptine (20 mg/kg,
      ip) exhibited a significant reduction of immobility time in the FST. These doses
      of the examined agents, which did have an effect in the FST, did not alter
      locomotor activity. The present study indicates that the antidepressant-like
      activity of tianeptine in the FST involves both NMDA and AMPA receptors and
      suggests that the interaction between serotonergic and glutamatergic transmission
      may play an important role in the action of tianeptine.

PMID- 22358101
TI  - Enhancement of the anti-immobility action of antidepressants by risperidone in
      the forced swimming test in mice.
AB  - The aim of the present study was to examine the effect of antidepressants (ADs)
      belonging to different pharmacological groups and risperidone (an atypical
      antipsychotic drug), given separately or jointly, on immobility time in the
      forced swimming test in male C57BL/6J mice. The antidepressants: citalopram,
      fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone
      in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time
      of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran
      (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline,
      reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and
      risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in
      the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited
      the effects induced by co-administration of ADs and risperidone. Active behavior
      in the forced swimming test was not a consequence of an increased general
      activity, since the combined treatment with ADs and risperidone failed to enhance
      the locomotor activity of mice. The obtained results indicate that a low dose of
      risperidone enhances the activity of ADs in an animal model of depression, and
      that, among other mechanisms, 5-HT(1A) receptors may play a role in these
      effects.

PMID- 22358102
TI  - Different pattern of changes in calcium binding proteins immunoreactivity in the
      medial prefrontal cortex of rats exposed to stress models of depression.
AB  - Reductions in the number and size of neurons in the medial prefrontal cortex
      (mPFC) have been documented in many post-mortem studies of depressed patients and
      animals exposed to stress. Here, we examined the effect of chronic unpredictable
      stress (CUS) and chronic mild stress (CMS) on specific populations of neurons in
      the rat mPFC. Antibodies directed against parvalbumin (PV), calbindin D-28K (CB)
      and active caspase-3 have been used to quantify the numerical density of PV
      immunoreactive (PV-ir), CB-ir and active caspase-3-ir cells, and to measure the
      relative optical density of neuropil. CUS decreased the density of CB-ir neurons
      and the optical density of CB-ir neuropil. In turn, CMS increased the densities
      of both CB-ir neurons and neuropil, while PV-ir neurons and PV-ir neuropil were
      not changed. The frequency distribution of neuronal surface areas was
      significantly different only for PV-ir neurons, and only between the control and
      CUS group. CMS reduced the density of active caspase-3-ir cells while CUS did
      not. We concluded that the mPFC reveals a different pattern of changes in neurons
      containing calcium binding proteins and active caspase-3 immunoreactivity in
      response to CUS and CMS.

PMID- 22358103
TI  - Anxiolytic-like effects of olanzapine, risperidone and fluoxetine in the elevated
      plus-maze test in rats.
AB  - In the present study was examined the effect of treatment with olanzapine or
      risperidone, given separately or in combination with fluoxetine, in the elevated
      plus-maze test (an animal model of anxiety) in male Wistar rats. The obtained
      results showed that treatment with olanzapine (1 mg/kg), risperidone (0.1 and 0.3
      mg/kg) or fluoxetine (5 and 10 mg/kg) induced an anxiolytic-like effect in the
      elevated plus-maze test. Olanzapine, risperidone and fluoxetine, tested in doses
      effective in the model of anxiolytic-like actions, did not affect motor
      coordination, while olanzapine (3 mg/kg) and risperidone (0.3 mg/kg) produced a
      significant reduction of exploratory activity in the open field test. In a
      combination study, the anxiolytic-like effect of olanzapine or risperidone was
      significantly antagonized by co-treatment with fluoxetine. Additionally, co
      treatment with olanzapine or risperidone and fluoxetine disturbed the motor
      coordination of rats in a rota-rod test. These findings indicate that olanzapine,
      risperidone and fluoxetine per se may be clinically effective in treating anxiety
      disorders, but their effects may be attenuated when they are used in combination
      with other medications.

PMID- 22358104
TI  - Effects of the histamine H3 receptor antagonist ABT-239 on acute and repeated
      nicotine locomotor responses in rats.
AB  - The addictive potential of nicotine is linked to psychomotor and cognition
      enhancing effects. Histamine (H)(3) receptor antagonism has similarly received
      attention for a role in cognition, however, the role of H(3) receptors are far
      less studied for affects on nicotine-induced locomotor responses. In the present
      study we tested whether the H(3) receptor antagonist 4-(2-{2-[(2R)-2
      methylpyrrolidinyl] ethyl}-benzofuran-5-yl) benzonitrile (ABT-239) influenced the
      psychomotor responses to acute and repeated nicotine, including sensitization and
      conditioned locomotion. ABT-239 (0.3-3 mg/kg) did not alter basal, nicotine
      evoked (0.4 mg/kg) locomotor responses, the expression of sensitization, or cue
      conditioned locomotion. However, in combination studies rats pretreated with a
      separate dose of ABT-239 (1 mg/kg) prior to nicotine (0.4 mg/kg) for 5 days and
      then challenged with nicotine (0.4 mg/kg) after a 5-day withdrawal period, showed
      significantly higher locomotor hyperactivity in comparison with the effect
      observed in nicotine-pretreated and challenged rats. Our findings implicate a
      limited role for H(3) receptors in locomotor responses to nicotine.

PMID- 22358105
TI  - Low-dose oral caffeine induces a specific form of behavioral sensitization in
      rats.
AB  - The present study assessed the effects of a low dose of orally administered
      caffeine on sensitization of open-field behavior in rats. Rats had free access to
      untreated water every day or water containing 0.2 mg/ml of caffeine every other
      day of the 14-day experiment. On alternate days discrete movements (horizontal
      and vertical) and ambulatory distance were measured in open-field activity
      monitors. Although caffeine intake significantly decreased across test sessions
      in caffeine-treated rats, the number of discrete horizontal movements
      significantly increased. These findings suggest that low doses of orally
      administered caffeine induce a specific form of behavioral sensitization in rats.

PMID- 22358106
TI  - Effects of PB190 and PB212, new sigma receptor ligands, on glucocorticoid
      receptor-mediated gene transcription in LMCAT cells.
AB  - The hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis is
      often observed in patients with major depression. It has even been implicated in
      the pathophysiology of this disease. Some antidepressant drugs (ADs) inhibit
      glucocorticoid receptor (GR) function under in vitro conditions. The sigma(1)
      receptor agonists reveal potential antidepressant activity in animals, moreover,
      igmesine is promising as an AD in humans. As already shown, sigma receptors are
      involved in stress-induced responses (e.g., conditioned fear stress in mice). The
      aim of the present study was to find out whether the new selective sigma receptor
      ligands, PB190 and PB212, are able to affect directly the endocrine system
      activity. To this end, we evaluated their influence on GR function in mouse
      fibroblast cells (L929), stably transfected with mouse mammary tumor virus
      chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). Fluvoxamine,
      a selective serotonin reuptake inhibitor, recognized as a sigma(1) receptor
      agonist was used for comparison. The obtained results showed that both PB190 and
      PB212 (potential sigma(1) receptor agonist and antagonist, respectively) like
      fluvoxamine, decreased the corticosterone-induced CAT activity in a concentration
      dependent manner. The significance of this fact remains ambiguous and requires
      further studies.

PMID- 22358107
TI  - Kynurenic acid: a new effector of valproate action?
AB  - We investigated the changes in hippocampal kynurenic acid (KYNA) concentrations
      and the amino acids involved in neuronal activity regulation following valproate
      (VPA) administration (400 mg/kg ip) in pentylenetetrazole-kindled rats (in vivo).
      We found a remarkably long-lasting increase in KYNA levels following VPA
      administration, and this effect correlated with a rise in GABA levels. No changes
      in the concentration of other analyzed amino acids were present. It is likely
      that the antiepileptic and neuroprotective properties of VPA may also be a
      consequence of an increase in the hippocampal KYNA concentration.

PMID- 22358108
TI  - Effects of simvastatin on the pharmacokinetics of diltiazem and its main
      metabolite, desacetyldiltiazem, after oral and intravenous administration in
      rats: possible role of P-glycoprotein and CYP3A4 inhibition by simvastatin.
AB  - The purpose of this study was to investigate the possible effects of
      hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, on
      the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in
      rats. HMG-CoA reductase inhibitors and diltiazem are sometimes prescribed as a
      combination therapy for the prevention or treatment of cardiovascular diseases.
      The effect of simvastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4
      activity was evaluated. Simvastatin inhibited CYP3A4 enzyme activity in a
      concentration-dependent manner with a 50% inhibition concentration (IC(50)) of
      3.0 MUM. In addition, simvastatin significantly enhanced the cellular
      accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. The
      pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined
      after oral and intravenous administration of diltiazem to rats in the presence
      and absence of simvastatin (0.3 and 1.0 mg/kg). The areas under the plasma
      concentration-time curve (AUC) and the peak concentration (C(max)) of diltiazem
      were significantly (p < 0.05, 1.0 mg/kg) increased by 45.2% and 35.2%,
      respectively, in the presence of simvastatin compared to control. Consequently,
      the absolute bioavailability (AB) values of diltiazem in the presence of
      simvastatin (1.0 mg/kg) were significantly (p < 0.05) higher (44.8%) than that of
      the control group. Moreover, the relative bioavailability (RB) of diltiazem was
      1.21- to 1.45-fold greater than that in the control group. The metabolite-parent
      AUC ratio (MR) in the presence of simvastatin (1.0 mg/kg) significantly decreased
      compared to the control group. This result implied that simvastatin effectively
      inhibited the metabolism of diltiazem. The increase in diltiazem oral
      bioavailability might be attributable to enhanced absorption in the small
      intestine via the inhibition of P-gp and to reduced first-pass metabolism of
      diltiazem via the inhibition of the CYP3A subfamily in the small intestine and/or
      in the liver rather than renal elimination of diltiazem by simvastatin.

PMID- 22358109
TI  - A generalized approach for iron catalyzed chemo- and regioselective formation of
      anti-Markovnikov acetals from styrene derivatives.
AB  - Fe(BF(4))(2).6H(2)O in the presence of pyridine-2,6-dicarboxylic acid and
      PhI(OAc)(2) can efficiently catalyze the formation of chemoselective dialkyl
      acetals from styrene derivatives with anti-Markovnikov regioselectivity in good
      to high yields under mild and benign reaction conditions.

PMID- 22358110
TI  - Lowest enthalpy polymorph of cold-compressed graphite phase.
AB  - Based on an ab initio evolutionary algorithm, a novel carbon polymorph with an
      orthorhombic Cmcm symmetry is predicted, named as C carbon, which has the lowest
      enthalpy among the previously proposed cold-compressed graphite phases.

PMID- 22358111
TI  - Radiological features of IgG4-related disease in the head, neck, and brain.
AB  - INTRODUCTION: Immunoglobulin (Ig) G4-related disease is a recently designated
      benign clinical entity histopathologically characterized by sclerosing
      inflammation and infiltration of numerous IgG4+ plasma cells that affects
      multiple organs. The purpose of this study is to characterize the imaging
      findings of patients with histopathologically proven IgG4-related disease in the
      head, neck, and brain. METHODS: A total of 17 patients (15 males, 2 females; mean
      age, 66.1 +/- 7.4 years) with histopathologically proven IgG4-related disease in
      the head, neck, and brain were identified in two hospitals between January 2004
      and December 2010. Imaging findings were retrospectively reviewed, with
      particular attention to the location and number of lesions, internal
      architecture, enhancement patterns, presence of vascular occlusion or
      compression, and changes in adjacent bones. RESULTS: The lesions, presented as
      either enlarged gland(s), or focal, localized nodules/masses, were distributed in
      the lacrimal gland (n = 7), the parotid gland (n = 14), the submandibular gland
      (n = 10), the pituitary gland (n = 2), skull base dura mater (n = 2), and the
      pterygopalatine fossa (n = 3). All lesions were well-defined and iso- to
      hypointense on T2-weighted magnetic resonance images and showed homogeneous
      enhancement. No lesion showed vascular occlusion or compression. Bones adjacent
      to the lesions showed remodeling (erosion or sclerosis) without signs of
      destruction (n = 6). Four patients had lesions involving multiple areas which
      extended along the trigeminal nerve, accompanied by expansion of neural foramina
      along their courses, with no signs of bone destruction. CONCLUSION: Sites of
      predilection for IgG4-related disease in the head, neck, and brain include the
      lacrimal, salivary, and pituitary glands. Recognition of the typical radiological
      features of IgG4-related disease, such as well-defined lesion borders, T2
      hypointensity, homogeneous and gradual enhancement pattern, absence of vascular
      occlusion or compression, and presence of bone remodeling without destruction,
      may be of help in the diagnosis of this benign clinical entity.

PMID- 22358113
TI  - Soft-templating synthesis of mesoporous graphitic carbon nitride with enhanced
      photocatalytic H2 evolution under visible light.
AB  - g-C(3)N(4) with worm-like pore and narrow pore size distribution was synthesized
      by using Pluronic P123 as soft-template. The worm-like porous g-C(3)N(4) not only
      possesses high BET surface area but also redshifts its absorbance edge up to 800
      nm, and shows photocatalytic activity even when the irradiation light lambda >
      700 nm.

PMID- 22358112
TI  - Reduction of intercellular adhesion molecule 1 may play a role in anti
      inflammatory effect of hyaluronic acid in a rat model of severe non-bacterial
      cystitis.
AB  - PURPOSE: To evaluate the impact of intercellular adhesion molecule 1 (ICAM-1) in
      hyaluronic acid (HA) therapy in rats model of severe non-bacterial cystitis.
      METHODS: Cystitis models in Sprague-Dawley female rats were produced by
      combination of intraperitoneal cyclophosphamide (CYP) with intravesical
      protamine/lipopolysaccharide (PS/LPS). HA or heparin (0.5 ml) was introduced
      intravesically to rats' bladders followed PS/LPS. Bladder tissue was prepared for
      histology including mast cell presence and measurement of ICAM-1, tumor necrosis
      factor (TNF)-alpha, and interleukin 6 (IL-6). RESULTS: Cystitis model using
      intraperitoneal CYP and intravesical SP/LPS showed serious inflammation, higher
      mast cell count with elevated ICAM-1, TNF-alpha, and IL-6 levels. After
      intravesical heparin or HA treatment, incidence of grades 3-4 bladder
      inflammation and tissue ICAM-1 level were only significantly lower in HA group (P
      = 0.017, P = 0.021, respectively), but not in heparin group (P = 0.12, P = 0.798,
      respectively). Remarkably lower level of TNF-alpha (P = 0.003) and ICAM-1 (P =
      0.006) was detected in HA-treated rats compared with heparin-treated rats.
      Inflammation grade and ICAM-1 level had strong correlation (P < 0.001). IL-6
      level after HA or heparin instillation had no difference. CONCLUSIONS:
      Intravesical administration of HA decreased the severity of bladder inflammation,
      mast cell presence, and levels of ICAM-1 and TNF-alpha in a rat model of severe
      non-bacterial cystitis; its effect was more obvious than that of heparin.
      Reduction of ICAM-1 may play a role in the anti-inflammatory effect of HA.

PMID- 22358115
TI  - Acidic gases and nitrate and sulfate particles in the atmosphere in the city of
      Guadalajara, Mexico.
AB  - Atmospheric concentrations of nitrous acid, nitric acid, nitrate and sulfate
      particles were obtained in this study from April to June 2008 in the center of
      the city of Guadalajara, while concentrations of ozone, sulfur dioxide, nitrogen
      dioxide and meteorological parameters (temperature and relative humidity), were
      acquired by the Secretaria del Medio Ambiente para el Desarrollo Sustentable del
      Estado de Jalisco (SEMADES). The results showed that nitric acid (2.7 MUg m(-3))
      was 2.7 times higher than nitrous acid (1.0 MUg m(-3)). The sulfur dioxide
      (SO(2)) concentration indicated an opposite trend to sulfate (SO(4) (2-)), with
      the average concentration of SO(2) (6.9 MUg m(-3)) higher in almost the entire
      period of study. The sulfur conversion ratio (Fs, 24.9%) and nitrogen conversion
      ratio (Fn, 6.2%), were revealed to be similar to that reported in other urban
      areas during warm seasons. It is also noted that ozone is not the main oxidizer
      of nitrogen dioxide and sulfur dioxide. This determination was made by taking
      into account the slightly positively correlation determined for Fn (r(2) = 0.084)
      and Fs (r(2) = 0.092) with ozone that perhaps suggests there are other oxidizing
      species such as the radical OH, which are playing an important role in the
      processes of atmospheric oxidation in this area.

PMID- 22358114
TI  - Comparison of hepatic and nephric total mercury concentrations between feral and
      ranch American mink (Neovison vison) from northwestern Poland.
AB  - For many years the American mink (Neovison vison) has been used in North America
      (where it originates from) as a sensitive indirect bioindicator in assessing the
      degree of mercury (Hg) contamination in terrestrial ecosystems. The aim of this
      paper was the determination of total concentrations of Hg in the liver and
      kidneys of feral and ranch mink from the Warta Mouth National Park (WMNP) and
      from farms located in northwestern Poland, for comparison with similar data on
      American mink from North America. In road-killed feral mink from the WMNP, the
      mean concentrations were 11.8 and 14.1 mg/kg dry weight in the liver and kidney,
      respectively. Mean Hg concentrations in feral mink were from 240 to 90 times
      higher in these two respective tissues than in ranch mink. The feral mink from
      northwestern Poland had concentrations of hepatic and nephric Hg similar to the
      highest concentrations that have been recorded over the past several decades in
      wild American mink from certain areas of Canada and the USA.

PMID- 22358116
TI  - Source apportionment of total suspended particulates in an arid area in
      southwestern Iran using positive matrix factorization.
AB  - The present study sough to apportion the possible sources of TSP in Ahvaz,
      southwestern Iran. A high correlation coefficient existed between measured and
      predicted values (R(2) = 0.99), indicating that the data were well modeled. Seven
      factors were resolved by the model: crustal dust (56%), road dust (7%), motor
      vehicles (8%), marine aerosol (9%), secondary aerosol (7%), metallurgical plants
      (4.5%), and finally petrochemical plants & fossil fuel combustion (8.5%). In
      contrast with crustal dust having higher relative contributions during spring and
      summer, motor vehicles had higher contributions during fall and winter. In
      addition, the latter had higher contributions during weekdays than weekends.

PMID- 22358117
TI  - Seasonal variation of polychlorinated biphenyls and organochlorine pesticide
      levels of sea and cultured farm fish in the Samsun region of Turkey.
AB  - The concentrations of selected Organochlorine (OC) pesticides (alpha-HCH, beta
      HCH, gamma-HCH, HCB, aldrin, 2,4'-DDE, 4,4'-DDE, 2,4'-DDT, 4,4'-DDT) and
      Polychlorinated Biphenyls (PCBs) (28, 70, 74, 81, 99, 101, 105, 118, 128, 138,
      153, 156, 170, 180, 183, 187) were measured in two species of cultured freshwater
      fish (rainbow trout, Oncornhychus mykiss and catfish, Silurus glanis) and two
      kinds of sea fish (mullet, Mugil cephalus and salmon, Salmo salar) between March
      2008 and June 2009 in order to evaluate the status, seasonal changes and
      potential sources of pollution in the Samsun region of Turkey. Concentrations of
      total PCBs ranged from 17.6 to 335 ng/g in rainbow trout, 1,063 to 3,234 ng/g in
      mullet, 21 to 1,887 ng/g in salmon and 108 to 1,172 ng/g lipid in catfish and
      total OC pesticide concentrations ranged from 303 to 473, 319 to 6,158, 101 to
      249 and 34 to 6,069 ng/g lipid in rainbow trout, mullet, salmon and catfish,
      respectively. It is concluded that the levels of persistent organic pollutants
      should be monitored regularly and rigorously by the appropriate government
      agency, with mandatory public reporting.

PMID- 22358118
TI  - Environmental risk presented by arsenic contamination of building and facility
      surfaces in a coking plant.
AB  - Arsenic contamination on the surface of buildings and facilities at a coking
      plant and associated health risk were studied. A total of 94 wipe samples from 56
      buildings and facilities were collected, and As concentrations were found to
      range from 0.01 to 23.90 MUg/100 cm(2). 20.2% of the samples exceeded the As
      level calculated to present health risk: 4.02 MUg/100 cm(2). Arsenic mean
      concentration was found to be highest on the surface of bricks, and coking zone
      showing the highest As risk. The findings of this study may provide clues to As
      pollution control and risk evaluation in coking plants.

PMID- 22358119
TI  - Metals in the tissues of two fish species from the rare and endemic fish nature
      reserve in the upper reaches of the Yangtze River, China.
AB  - Concentrations of copper, zinc, mercury, and arsenic were measured in the muscle,
      gill and liver tissues of Coreius heterodon and Pelteobagrus vachelli collected
      from the rare and endemic fish nature reserve in the upper reaches of the Yangtze
      River. The concentrations of copper and zinc in the tissues of these two fish
      species were higher than those of mercury and arsenic. Highest metal
      concentrations were generally found in fish samples from Yibin. The
      concentrations of copper, zinc, mercury, and arsenic in C. heterodon were higher
      than that in P. vachelli. The fish from this study area were not safe for human
      consumption.

PMID- 22358120
TI  - Internet cigarette sales and Native American sovereignty: political and public
      health contexts.
AB  - Internet cigarette vendors (ICVs) advertise low prices for tobacco products,
      subverting public health policy efforts to curtail smoking by raising prices.
      Many online retailers in the United States claim affiliation with Native American
      tribes and share in tribal tax-free status. Sales of discounted cigarettes from
      both online vendors and brick-and-mortar stores have angered non-Native retailers
      and triggered enforcement actions by state and federal governments in the United
      States concerned over lost cigarette excise tax revenue. Examination of the
      history and politics of cigarette sales on reservations and attempts to regulate
      Internet cigarette sales highlights the potential role for greater use of
      negotiated intergovernmental agreements to address reservation-based tobacco
      sales. Our review notes global parallels and explicates history and politics of
      such regulation in the United States, and offers background for collaborative
      efforts to regulate tobacco sales and decrease tobacco use.

PMID- 22358121
TI  - National trends and coding patterns in fall-related mortality among the elderly
      in the United States.
AB  - Because good information on deaths caused by a fall would be important for
      prevention policies, we analyzed the influence of coding differences on
      variability in state-level fall death rates in the elderly. We examined state
      differences in the number of cause of death codes on death certificates, death
      certifiers, completeness of E-coding, and indicators of specificity of coding. We
      found that state-specific fall mortality rates ranged from 13.9 to 140.4 in
      people aged 65 years and above. States employing a coroner to investigate injury
      deaths had 14 per cent fewer recorded fall deaths than those where a medical
      examiner conducted the investigations. Each unit increase in the median number of
      cause of death codes was associated with a 10 per cent increase in the number of
      falls. For each 1 per cent increase in the use of unspecified codes for the
      underlying cause of death, the number of falls dropped by 2 per cent. Current
      fall mortality data do not appear to identify all instances of falls. Variability
      in unintentional fall-related death rates among states may be partly explained by
      death certification coding practices. Standardization of coding and training for
      documentation of fall events and death certificate reporting could help uncover
      the actual fall mortality burden in the elderly.

PMID- 22358122
TI  - Commentary: death certificate reporting needs to be fixed.
AB  - Something is wrong with the death reporting when there is a fivefold difference
      in the reported rates of fall mortality between Alabama and Vermont, two states
      in the United States. The problem is not unique here, as even the Swedish have
      trouble with their death certificate data. We understand that some of the reason
      is poor reporting, but how do we figure out how to do it right?

PMID- 22358123
TI  - Ramosetron, dexamethasone, and their combination for the prevention of
      postoperative nausea and vomiting in women undergoing laparoscopic
      cholecystectomy.
AB  - BACKGROUND: In this randomized and controlled study, we evaluated the antiemetic
      efficacy of ramosetron combined with dexamethasone for postoperative nausea and
      vomiting (PONV) compared with that of dexamethasone or ramosetron alone in women
      who underwent laparoscopic cholecystectomy. METHODS: One hundred twenty female
      patients were randomly assigned to one of three groups to receive antiemetics as
      follows: ramosetron 0.3 mg (group R), dexamethasone 8 mg (group D), or ramosetron
      0.3 mg combined with dexamethasone 8 mg (group RD). PONV, postoperative pain
      intensity, rescue antiemetics requirement, and side effects were assessed at 0-6,
      6-12, and 12-24 h after surgery. RESULTS: The ratio of complete response (no PONV
      and no rescue antiemetic) was higher at 6-12 h in groups R and RD than in group D
      (p < 0.05) and at 12-24 h in group RD than in group D (p < 0.05). The incidence
      of nausea was lower at 6-12 h in groups R (p = 0.043) and RD (p = 0.003) compared
      to group D and at 12-24 h in group RD (p = 0.01) compared to group D. The
      severity of nausea was also significantly reduced at 6-12 h in groups R and RD
      compared to group D (p < 0.05). There were no clinically serious adverse events
      related to the studied drugs. CONCLUSION: Antiemetic efficacy of the combination
      of ramosetron 0.3 mg and dexamethasone 8 mg for PONV was most superior, with 93%
      of the patients showing complete response at 12-24 h after surgery followed by
      ramosetron alone and dexamethasone alone.

PMID- 22358124
TI  - Intramural acellular porcine dermal matrix (APDM)-assisted gastrotomy closure for
      natural orifice transluminal endoscopic surgery (NOTES).
AB  - BACKGROUND: A highly reliable and safe means of gastric closure for natural
      orifice transluminal endoscopic surgery (NOTES) has yet to be developed. The
      authors have previously described the self-approximating transluminal access
      technique (STAT) as a means for gastrotomy closure in transgastric surgery. It
      has yet to be determined whether biologic mesh can be utilized in facilitating
      gastrotomy closure via STAT. The aim of this study was to determine the
      feasibility of implanting an acellular porcine dermal matrix (LifeCell) into the
      STAT tunnel and investigate whether it will become incorporated into the
      submucosal plane of the STAT tunnel. METHODS: Five pigs underwent transgastric
      left uterine horn resection utilizing STAT. For closure, the acellular porcine
      dermal matrix was implanted within the submucosal plane, occluding the
      seromuscular incision. The mucosal incision was then closed over the matrix with
      endoscopically placed clips. Necropsy was performed after a 3 week survival
      period. Histopathological evaluation of the tunnel and matrix was performed.
      RESULTS: The matrix was successfully implanted in all five animals. Average OR
      time was 151 +/- 68 min. Average time to anchor and embed the matrix within the
      tunnel was 4 +/- 1 and 9 +/- 12 min, respectively. There was one duodenal
      perforation related to a balloon occlusion device. Postoperative course was
      unremarkable; the average weight gain at 3 weeks was 22 +/- 5 lbs. On necropsy,
      one animal had some protrusion of the matrix at the serotomy, with adhesions to
      small bowel and liver. Histopathology revealed one clinically insignificant
      microabscess but otherwise demonstrated local inflammation and fibrovascular
      ingrowth into the matrix. CONCLUSIONS: The porcine dermal matrix can be
      successfully implanted within the gastric submucosal plane and evidence of
      incorporation into the gastric wall by 3 weeks was demonstrated.

PMID- 22358126
TI  - Outcome of laparoscopic major liver resection for colorectal metastases.
AB  - BACKGROUND: Minimally invasive liver resection (MILR) for colorectal liver
      metastases (CRLM) is gaining widespread acceptance. However, data are still
      lacking on the feasibility, long- and short-term outcomes of laparoscopic major
      hepatectomy (i.e., three or more liver segments). METHODS: Between October 2002
      and December 2008, prospectively collected data of 117 patients who underwent
      major liver resection [97 open (OMLR) and 20 laparoscopic (LMLR) procedures] for
      CRLM were analyzed. Twenty patients in the LMLR group were matched with 20
      patients of the OMLR based on 13 parameters. We compared the long- and short-term
      outcomes between these two groups. RESULTS: Median duration of surgery was 257.5
      (range 75-360) min in LMLR versus 232.5 (range 120-400) min in OMLR (P = 0.228).
      Median blood loss during surgery was 550 ml in each group (range 100-4,000 vs.
      100-2,500 ml, P = 0.884). There was no statistically significant difference in
      the rate of postoperative complications (both severity and location). Median
      magnitude of tumor-free resection margin was 7.5 versus 5.5 mm in the laparoscopy
      versus open group, respectively (P = 0.651). Median disease-free survival (DFS)
      of the entire study population was 18.4 months [95% confidence interval (CI) 11.9
      50.0 months]. Median overall survival (OS) was 50.7 months (95% CI 36.2 months to
      undetermined). The estimated DFS and OS rates at 1, 2, and 5 years were
      comparable in the two groups (P = 0.637 and 0.872, respectively). CONCLUSION:
      Laparoscopic MLR for selected CRLM is feasible and might result in comparable
      oncologic outcomes as in open liver resection.

PMID- 22358127
TI  - The promise of computer-assisted auscultation in screening for structural heart
      disease and clinical teaching.
AB  - Cardiac auscultation has been the central clinical tool for the diagnosis of
      valvular and other structural heart diseases for over a century. Physicians
      acquire competence in this technique through considerable training and
      experience. In Africa, however, we face a shortage of physicians and have the
      lowest health personnel-to-population ratio in the world. One of the proposed
      solutions for tackling this crisis is the adoption of health technologies and
      product innovations to support different cadres of health workers as part of task
      shifting. Computer-assisted auscultation (CAA) uses a digital stethoscope
      combined with acoustic neural networking to provide a visual display of heart
      sounds and murmurs, and analyses the recordings to distinguish between innocent
      and pathological murmurs. In so doing, CAA may serve as an objective tool for the
      screening of structural heart disease and facilitate the teaching of cardiac
      auscultation. This article reviews potential clinical applications of CAA.

PMID- 22358129
TI  - Vibrational dynamics of acetate in D2O studied by infrared pump-probe
      spectroscopy.
AB  - Solute-solvent interactions between acetate and D(2)O were investigated by
      vibrational spectroscopic methods. The vibrational dynamics of the COO asymmetric
      stretching mode in D(2)O was observed by time-resolved infrared (IR) pump-probe
      spectroscopy. The pump-probe signal contained both decay and oscillatory
      components. The time dependence of the decay component could be explained by a
      double exponential function with time constants of 200 fs and 2.6 ps, which are
      the same for both the COO asymmetric and symmetric stretching modes. The Fourier
      spectrum of the oscillatory component contained a band around 80 cm(-1), which
      suggests that the COO asymmetric stretching mode couples to a low-frequency
      vibrational mode with a wavenumber of 80 cm(-1). Based on quantum chemistry
      calculations, we propose that a bridged complex comprising an acetate ion and one
      D(2)O molecule, in which the two oxygen atoms in the acetate anion form hydrogen
      bonds with the two deuterium atoms in D(2)O, is the most stable structure. The 80
      cm(-1) low-frequency mode was assigned to the asymmetric stretching vibration of
      the hydrogen bond in the bridged complex.

PMID- 22358130
TI  - Photocatalytic oxidation surfaces on anatase TiO2 crystals revealed by single
      particle chemiluminescence imaging.
AB  - We report a single-particle approach for studying the photocatalytic oxidation
      reaction on individual anatase TiO(2) particles. Single-particle kinetic and
      imaging analyses of the chemiluminescence (CL) emitted from the probe dye
      molecules revealed that the oxidation reactivity is not significantly dependent
      on the crystal faces.

PMID- 22358128
TI  - The medicinal leech genome encodes 21 innexin genes: different combinations are
      expressed by identified central neurons.
AB  - Gap junctional proteins are important components of signaling pathways required
      for the development and ongoing functions of all animal tissues, particularly the
      nervous system, where they function in the intracellular and extracellular
      exchange of small signaling factors and ions. In animals whose genomes have been
      sufficiently sequenced, large families of these proteins, connexins, pannexins,
      and innexins, have been found, with 25 innexins in the nematode Caenorhabditis
      elegans Starich et al. (Cell Commun Adhes 8: 311-314, 2001) and at least 37
      connexins in the zebrafish Danio rerio Cruciani and Mikalsen (Biol Chem 388:253
      264, 2009). Having recently sequenced the medicinal leech Hirudo verbana genome,
      we now report the presence of 21 innexin genes in this species, nine more than we
      had previously reported from the analysis of an EST-derived transcriptomic
      database Dykes and Macagno (Dev Genes Evol 216: 185-97, 2006); Macagno et al.
      (BMC Genomics 25:407, 2010). Gene structure analyses show that, depending on the
      leech innexin gene, they can contain from 0 to 6 introns, with closely related
      paralogs showing the same number of introns. Phylogenetic trees comparing Hirudo
      to another distantly related leech species, Helobdella robusta, shows a high
      degree of orthology, whereas comparison to other annelids shows a relatively low
      level. Comparisons with other Lophotrochozoans, Ecdyzozoans and with vertebrate
      pannexins suggest a low number (one to two) of ancestral innexin/pannexins at the
      protostome/deuterostome split. Whole-mount in situ hybridization for individual
      genes in early embryos shows that ~50% of the expressed innexins are detectable
      in multiple tissues. Expression analyses using quantitative PCR show that ~70% of
      the Hirudo innexins are expressed in the nervous system, with most of these
      detected in early development. Finally, quantitative PCR analysis of several
      identified adult neurons detects the presence of different combinations of
      innexin genes, a property that may underlie the participation of these neurons in
      different adult coupling circuits.

PMID- 22358131
TI  - Arsenic metabolism and thioarsenicals.
AB  - Arsenic has received considerable attention in the world, since it can lead to a
      multitude of toxic effects and has been recognized as a human carcinogen causing
      cancers. Here, we focus on the current state of knowledge regarding the proposed
      mechanisms of arsenic biotransformation, with a little about cellular uptake,
      toxicity and clinical utilization of arsenicals. Since pentavalent methylated
      metabolites were found in animal urine after exposure to iAs(III), methylation
      was considered to be a detoxification process, but the discovery of methylated
      trivalent intermediates and thioarsenicals in urine has diverted the view and
      gained much interest regarding arsenic biotransformation. To further investigate
      the partially understood phenomena relating to arsenic toxicity and the uses of
      arsenic as a drug, it is important to elucidate the exact pathways involved in
      metabolism of this metalloid, as the toxicity and the clinical uses of arsenic
      can be best recognized in context of its biotransformation. Thereby, in this
      perspective, we have focused on arsenic metabolic pathways including three
      proposed mechanisms: a classic pathway by Challenger in 1945, followed by a new
      metabolic pathway proposed by Hayakawa in 2005 involving arsenic-glutathione
      complexes, while the third is a new reductive methylation pathway that is
      proposed by our group involving As-protein complexes. According to previous and
      present in vivo and in vitro experiments, we conclude that the methylation
      reaction takes place with simultaneous reductive rather than stepwise oxidative
      methylation. In addition, production of pentavalent methylated arsenic
      metabolites are suggested to be as the end product of metabolism, rather than
      intermediates.

PMID- 22358133
TI  - Heat shock protein magic in antigen trafficking within dendritic cells:
      implications in antigen cross-presentation in immunity.
AB  - Dendritic cells (DCs) take up soluble- or cell-associated antigens and digest
      them, delivering fragments to the MHC class I pathway to display antigenic
      peptides to CD8(+) T cells, a process known as cross-presentation. The pathway
      requires that, in order to be degraded by proteosomes, the extracellular antigens
      must have access to the cytosol across the endosomal membranes. Although the
      cross-presentation phenomena was first identified in the 1970s, the molecular
      mechanism responsible for the translocation is still not fully understood. In
      this context, we have recently found that cytosolic heat shock protein (HSP)90
      translocates internalized antigen to the cytosol in DCs. Our results revealed the
      important role that cytosolic HSP90 plays in cross-presentation by pulling out
      endosomal antigen to the cytosol.

PMID- 22358132
TI  - Treatment response and evolution of HBV resistance during lamivudine plus
      adefovir or entecavir therapy in patients with adefovir-resistant mutants.
AB  - BACKGROUND: Here, we investigated the treatment response and evolution of HBV
      resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV)
      monotherapy in patients with ADV-resistant mutants. METHODS: Of the 53 patients
      with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV
      group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median
      24 months and range 12-67 months). RESULTS: During 24 months therapy, no
      significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200
      copies/ml, hepatitis B e antigen loss and ALT normalization between the two
      groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had
      higher rates of undetectable HBV DNA than those with the double mutant
      rtA181T/V+rtN236T at months 3-18 of therapy. No virological breakthrough occurred
      except for one patient with rtN236T resistant mutation who experienced
      virological and biochemical breakthrough after the emergence of an additional
      rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV
      monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV
      resistant mutations and virological breakthrough at months 12, 24 and 36 were
      3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly
      replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant
      mutations. CONCLUSIONS: There was no significant difference in virological
      response between the LAM+ADV and ETV groups in patients with ADV-resistant
      mutants. LAM+ADV were less effective in patients with the double mutant
      rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV
      resistant mutation was high in patients with LAM/ADV-resistant mutants treated
      with ETV monotherapy.

PMID- 22358134
TI  - Preclinical safety and efficacy of in situ REIC/Dkk-3 gene therapy for prostate
      cancer.
AB  - The preclinical safety and therapeutic efficacy of adenoviral vectors that
      express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in
      prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously
      demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we
      herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC
      administration was examined for toxicity and therapeutic effects in a
      subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra
      prostatic Ad-mREIC administration was tested for toxicity in normal mice. The
      whole-body and spleen weights, hematological and serum chemistry parameters, and
      histological evaluation of tissues from throughout the body were analyzed. Both
      experiments indicated that there was no significant difference in the examined
      parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ
      treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic
      effect was observed after Ad-hREIC treatment. Confirming this observation, the
      robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo
      subcutaneous prostate cancer model. Based on the results of these preclinical
      experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy
      to be safe and useful for the clinical treatment of prostate cancer.

PMID- 22358135
TI  - Measurements and evaluation of proximal femoral bone mineral density with dual
      energy X-ray absorptiometry.
AB  - Proximal femoral bone mineral density (BMD) can be measured by dual energy X-ray
      absorptiometry method in the neck, trochanter, intertrochanter, total and Ward's
      triangle area. Ward's triangle area of the proximal femur is a smaller area to
      measure than the others, and the position varies, depending on the status of
      inner rotation of the target leg. In this study, the measurements of the proximal
      femoral BMD in women were carried out on the neck, trochanter, intertrochanter,
      total and Ward's triangle area with the, subjects' legs turned 15 degrees toward
      the inside. The Ward's BMD were measured using Ward's cognitive method, in which
      the measured BMD were compared among age groups of 50-59, 60-69, 70-79 and 80-89
      to determine whether this process could reveal decreased femoral BMD in elderly
      women. The correlation between BMD and age was tested using the Pearson
      correlation coefficient. In all measured parts, the BMD of women age 50-59 were
      significantly higher than those of women age 80-89. The correlations between BMD
      and age were negative in all measured parts, and the most negative correlation
      was between age and Ward's BMD. The study using Ward's cognitive method showed an
      inverse correlation between Ward's BMD and age in women.

PMID- 22358136
TI  - Laparoscopic-assisted tension-free vaginal mesh: an innovative approach to
      placing synthetic mesh: transvaginally for surgical correction of pelvic organ
      prolapse.
AB  - Polypropylene mesh implants for the correction of pelvic organ prolapse (POP) are
      now available in Japan. We developed an innovative approach for correcting POP by
      placing polypropylene mesh transvaginally with laparoscopic assistance. From June
      2007 through March 2010, sixteen consecutive patients with symptomatic stage 2 or
      3 pelvic organ prolapse underwent the laparoscopic-assisted tension-free vaginal
      mesh procedure at Okayama University Hospital. All patients were evaluated before
      and at 1, 3, 6, and 12 months after surgery. Female sexual function was also
      evaluated with the Female Sexual Function Index (FSFI). The procedure was
      performed successfully without significant complications. Fifteen of 16 patients
      were considered anatomically cured (93.8%) at 12 months postoperatively. One
      patient with a recurrent stage 3 vaginal vault prolapse required sacral colpopexy
      six months postoperatively. Total FSFI scores improved significantly from 10.3 +/
      1.3 at baseline to 18.0 +/- 1.2 at 12 months after surgery. The laparoscopic
      assisted trans-vaginal mesh is a safe, effective, and simple procedure for POP
      repairs. The procedure not only restores anatomic relationships but also improves
      sexual function.

PMID- 22358137
TI  - Quantitative assessment of gait bradykinesia in Parkinson's disease using a
      portable gait rhythmogram.
AB  - To quantify gait bradykinesia during daily activity in patients with Parkinson's
      disease (PD), we measured movement-induced accelerations over more than 24h in 50
      patients with PD and 17 age-matched normal controls, using a new device, the
      portable gait rhythmogram. Acceleration values induced by various movements,
      averaged each 10 min, exhibited a gamma distribution. The mean value of the
      distribution curve was used as an index of the "amount of overall movement per
      24h". Characteristic changes were observed in both the gait cycle and gait
      acceleration. During hypokinesia, the gait cycle became either faster or slower.
      A number of patients with marked akinesia/bradykinesia showed a reduced and
      narrow range of gait acceleration, i.e., a range of floor reaction forces. The
      results suggest that assessment of the combination of changes in gait cycle and
      gait acceleration can quantitatively define the severity of gait bradykinesia.

PMID- 22358138
TI  - Preferable forms of relaxation for health promotion, and the association between
      recreational activities and self-perceived health.
AB  - Little research has been done on the association between relaxation and health.
      In the present study, by conducting a nationwide cross-sectional survey, we aimed
      to obtain scientific data on the preferable forms of relaxation for health
      promotion, and to clarify the associations between specific recreational
      activities and self-perceived mental and physical health. We selected 4,000
      households by stratified random sampling from across Japan in November 2009 and
      used the interview method to collect data (number of subjects: 2,206). The
      questionnaire contained items on sleep, recreation status, recreational
      activities, and self-perceived mental and physical health status. We obtained
      responses from 1,224 adults (response rate: 55.5%). Insufficient rest from sleep,
      short sleep duration (<6 h/day), ineffective use of free time, and less free time
      used for activities other than rest showed independent positive associations with
      poor mental and physical health. The results of the logistic regression analyses
      showed significantly low adjusted odds ratios with regard to the status of poor
      mental and physical health for outings/walking among men (0.33 [95% confidence
      interval; 0.16-0.68] and 0.49 [0.26-0.90], respectively), and for community
      activities among women (0.19 [0.04-0.79] and 0.27 [0.09-0.77], respectively).
      Relaxation for the promotion of health should include both passive relaxation
      (rest) and active relaxation (recreation). In addition, ensuring sufficient sleep
      duration is important for passive relaxation, and engaging in outings/walking for
      men and community activities for women are important for active relaxation.

PMID- 22358139
TI  - The pretreatment of maximum standardized uptake values (SUVmax) of the primary
      tumor is predictor for poor prognosis for patients with epithelial ovarian
      cancer.
AB  - The purpose of this study was to evaluate prognostic factors for epithelial
      ovarian cancer. We found that the pretreatment values of maximum standardized
      uptake (SUVmax) of the primary tumor by positron emission tomography/computed
      tomography (PET/CT), tumor marker CA125 and C-reactive protein (CRP) were
      correlated with clinical characteristics and prognosis for such patients. The
      clinical parameters and prognoses and their correlations with SUVmax of primary
      tumor, CA125 and CRP were examined for 51 patients with primary ovarian cancer.
      The SUVmax of the primary tumor had a statistically significant association with
      stage (p = 0.010) and histology (p = 0.001). CA125 was significant associated
      with stage (p = 0.011), histology (p = 0.005) and lymph node metastasis (p =
      0.025). CRP was also significantly associated with stage (p = 0.049). Disease
      free survival rates of patients exhibiting a high SUVmax, CA125 and CRP were
      significantly lower than those exhibiting a low SUVmax, CA125 and CRP levels (p =
      0.008, 0.034, and 0.037, respectively). Furthermore, overall survival rates of
      patients exhibiting a high SUVmax were significantly lower than those exhibiting
      a low SUVmax (p = 0.049).The high SUVmax of primary tumor is an important factor
      for identifying ovarian cancer patients with a predictor for poor prognosis.

PMID- 22358140
TI  - Frequent use of fresh frozen plasma is a risk factor for venous thrombosis in
      extremely low birth weight infants: a matched case-control study.
AB  - Percutaneously inserted central catheters (PICCs) are often used in neonatal
      medicine. Venous thrombosis (VT) is one of the complications associated with PICC
      use. According to some reports, fresh frozen plasma (FFP) may be a risk factor
      for VT. The purpose of this study was to determine whether FFP use is associated
      with VT in extremely low birth weight infants (ELBWIs). We performed a matched
      case-control study on risk factors for VT in ELBWIs born over a period of 5 years
      in the neonatal intensive care unit of a tertiary hospital. Controls were infants
      from the unit matched for gestational age and birth weight. We performed
      univariate analyses and created receiver operating characteristic (ROC) curves
      for the cut-off values of continuous parameters such as FFP. We also conducted
      multivariate conditional logistic regression analysis and calculated adjusted
      odds ratios and their 95% confidence intervals. Thirteen VT cases and 34 matched
      controls were examined. Using an ROC curve, FFP by day 5 > 50 mL/kg was selected
      as the cut-off value. In multivariate conditional logistic regression analysis,
      FFP by day 5 > 50 mL/kg exhibited an adjusted odds ratio of 5.88 (95% confidence
      interval: 1.12-41.81, p = 0.036). FFP by day 5 > 50 mL/kg may be a risk factor
      for VT in ELBWIs.

PMID- 22358141
TI  - Relationship between tourniquet pressure and a cross-section area of superficial
      vein of forearm.
AB  - This study investigated the appropriate tourniquet pressure (TP) and duration of
      tourniquet application for venipuncture by calculating the venous cross-section
      (VCS) area on ultrasonography. Twenty healthy volunteers without cardiovascular
      risk factors were enrolled in this study. A target vein (either a cephalic or
      median cubital vein) was selected on ultrasonography. The pneumatic tourniquet
      was inflated using a rapid cuff inflator system at setting pressure for 120 sec.
      TP strength was varied from 20 mmHg to 100 mmHg, in 20 mmHg increments. The order
      of TP was randomized. Comparisons among more than 3 groups were performed by one
      way repeated-measures ANOVA and the Bonferroni method. The VCS area increased
      rapidly until 10 sec after tourniquet inflation. The VCS area then increased
      gradually until 30 sec after tourniquet inflation. After that, the VCS area did
      not increase remarkably. The VCS area increased with TP strength up to 80 mmHg,
      but the VCS area at TP 100 mmHg decreased to less than that at TP 40 mmHg. Based
      on these results, we recommend a tourniquet pressure of 60 mmHg, and duration of
      tourniquet application is 30 to 60 sec for venipuncture.

PMID- 22358142
TI  - Giant-cell tumor of the patella.
AB  - We report a 38-year old man with a giant-cell tumor in a rare site, the patella.
      Primary patellar neoplasms are highly unusual. According to a survey by the Bone
      and Soft Tissue Tumor Committee of the Japanese Orthopaedic Association, of more
      than 2,126 giant-cell tumors of bone reported since 1972, only 22 were primary
      patellar neoplasms. We present a case of this rare entity along with its clinical
      and radiographic features. The first clinical symptom was anterior knee pain.
      Though anterior knee pain has numerous and varied causes, it is necessary to
      consider patellar bone tumors in the differential diagnosis.

PMID- 22358143
TI  - Dominant vertebral artery injury during posterior atlantoaxial transarticular
      screw fixation in a juvenile rheumatoid arthritis patient with atlantoaxial
      subluxation.
AB  - Many authors have reported on iatrogenic vertebral artery (VA) injury, but, to
      our knowledge, this is the first report of a dominant VA injury with compensatory
      blood flow from the hypoplastic VA. A 23-year-old woman with juvenile rheumatoid
      arthritis and atlantoaxial subluxation sustained injury to her dominant VA after
      occipitocervical fusion using transarticular screws. This did not result in
      lethal consequences due to compensation from her hypoplastic contralateral VA.
      Postoperative angiography, however, illustrated occlusion of the dominant left
      side, while the hypoplastic VA of the right side was enlarged. The patient
      experienced vertigo and loss of consciousness several times during
      rehabilitation. At the 4-year follow-up exam, bony fusion was observed, with no
      neurological deficits or correction loss. She had had no episodes of
      unconsciousness and no recurrence of any symptoms over the previous 3 years.

PMID- 22358144
TI  - Mortality attributable to occupational exposure in Sweden.
AB  - OBJECTIVES: The objective of this study was to estimate the mortality from
      cancer, cardiovascular, and respiratory diseases attributable to occupational
      exposure in Sweden. METHODS: Estimates were calculated for men and women
      separately, and we considered only deaths between 25-74 years of age. We
      considered cancer exposures/sites classified as I or 2a according to the
      International Agency for Research on Cancer (IARC). Acute myocardial infarction
      was the only included cardiovascular disease. Respiratory diseases comprised
      chronic obstructive pulmonary disease (COPD) asthma, pneumoconiosis and
      alveolitis. All deaths of pneumoconiosis and alveolitis were considered work
      related. Estimates were based on the Swedish mortality in 2007. RESULTS: In
      total, we estimate that there are about 800 work-related deaths per year in the
      studied causes. The majority are due to acute myocardial infarction, with 126
      deaths among women and 337 deaths among men attributable to job strain, shift
      work, exhaust gases, combustion products, or environmental tobacco smoke (ETS).
      There are 99 respiratory disease-related deaths, the vast majority from COPD
      (N=92). In total, 270 cancer deaths are estimated to be work-related. For men,
      half of the cases are attributed to asbestos exposure. CONCLUSIONS: Our results
      indicate that preventive measures to decrease occupational mortality should
      consider factors associated with myocardial infarction such as job strain, shift
      work and exhaust gases from vehicles and combustion products. Exposures to
      factors associated with COPD, such as dust, also seem important to prevent.

PMID- 22358145
TI  - Thermodynamic and structural insight into the underlying mechanisms of the
      phosphatidylcholine liposomes - casein associates co-assembly and functionality.
AB  - The combination of data obtained from isothermal mixing calorimetry and light
      scattering allowed us to reveal the relationships between the character of the
      interactions of casein (beta-casein and sodium caseinate (SCN) particles) with
      phosphatidylcholine (PC) liposomes and their specific properties, such as, the
      hydrophilic-lipophilic balance of the surface properties, the size, and the
      architecture. The size distribution diagrams, obtained by dynamic light
      scattering for the particles of pure PC, beta-casein and their complexes,
      indicated the involvement of both the protein and liposome particles in the
      complex formation at pH 5.5 and low ionic strength (0.001 M). As this took place,
      the data of the extraction of the free PC from the aqueous solutions of the
      complex particles by diethyl ether showed about 90% of the binding of the PC
      liposomes by the beta-casein particles. As a result of the interactions, the
      complex particles showed markedly higher values of their density, calculated on
      the basis of the light scattering data, as compared to the ones, which were
      inherent to the pure protein particles. The generality of the importance of such
      a structural parameter as the density of the complex (protein + PC) particles for
      their function as protectors against oxidation for the unsaturated PC was
      supported by the data obtained for the complex particles formed between SCN and
      PC liposomes at pH 5.5, 40  degrees C and the low ionic strength (0.001 M). In
      addition, the importance of both the density and the architecture of the complex
      (protein + PC) particles for their susceptibility to the proteolysis in the
      gastrointestinal tract was illustrated by the example of the proteolysis of the
      complex (beta-casein + PC) particles in the simulated gastrointestinal conditions
      in vitro.

PMID- 22358146
TI  - IgA antibodies against beta2 glycoprotein I in hemodialysis patients are an
      independent risk factor for mortality.
AB  - Cardiovascular complications are the most important cause of death in patients on
      dialysis with end-stage renal disease. Antibodies reacting with beta-glycoprotein
      I seem to play a pathogenic role in antiphospholipid syndrome and stroke and are
      involved in the origin of atherosclerosis. Here we evaluated the presence of
      anticardiolipin and anti-beta-glycoprotein I antibodies together with other
      vascular risk factors and their relationship with mortality and cardiovascular
      morbidity in a cohort of 124 hemodialysis patients prospectively followed for 2
      years. Of these, 41 patients were significantly positive for IgA anti-beta
      glycoprotein I, and the remaining had normal values. At 24 months, overall and
      cardiovascular mortality and thrombotic events were all significantly higher in
      patients with high anti-beta-glycoprotein I antibodies. Multivariate analysis
      using Cox regression modeling found that age, hypoalbuminemia, use of dialysis
      catheters, and IgA beta-glycoprotein I antibodies were independent risk factors
      for death. Thus, IgA antibodies to beta-glycoprotein I are detrimental to the
      clinical outcome of hemodialysis patients.

PMID- 22358147
TI  - Anatomic configuration affects the flow rate and diameter of porcine
      arteriovenous fistulae.
AB  - Although arteriovenous fistulae are currently the preferred form of vascular
      access, early failure is a significant problem. Since wall shear stress is
      thought to play an important role in the pathogenesis of early failure, and this
      stress varies markedly in different fistula configurations, we assessed the
      influence of configuration (curved or straight) on longitudinal changes of flow
      rate and lumen diameter in a porcine fistula model. Fistulae were created in
      eight pigs between the femoral artery and vein, with each animal having a curved
      and a straight configuration on opposite sides. Velocity measurements were
      obtained by ultrasound at the time of surgery and at intermediate time points up
      to 28 days. Quantification of both the configuration and the internal diameter of
      the fistulae was determined by CT scans. The overall rate of increased flow
      during each time interval (0 to 2 days, 2 to 7 days, and 7 to 28 days) was more
      pronounced with the curved fistulae. Moreover, the luminal diameter of curved
      fistulae had dilated more from the time of surgery to 28 days as compared to the
      straight fistulae. Thus, anatomical configuration of fistulae plays a major role
      in flow-mediated dilatation. Identifying the optimal configuration may result in
      increased diameter and consequently blood flow, and perhaps reduce the incidence
      of early failure.

PMID- 22358149
TI  - Acid induced acetylacetonato replacement in biscyclometalated iridium(III)
      complexes.
AB  - Biscyclometalated iridium(III) complexes with an ancillary acetylacetone ligand,
      Ir(L)(2)(acac), (L = 2-(benzo[b]thiophen-2-yl)pyridine (btp), 1
      phenylisoquinoline (piq), 2-phenylbenzothiazole (bt), 2-phenylpyridine (ppy),
      acac = deprotonated acetylacetone), demonstrate spectroscopic changes in their UV
      Vis absorption and luminescent emission under acidic conditions. Such changes
      were found to be the same as those observed when certain mercury salts exist in
      the systems. Because some iridium(III) complexes have sulfur-containing ligands
      (i.e., btp and bt), a question was then raised as for whether or not the
      spectroscopic changes are associated with the specific affinity of Hg(2+) to the
      sulfur atom. Extensive studies performed in this work unambiguously proved that
      the observed spectroscopic changes were solely the results of the acid induced
      departure of acac and the follow-up coordination of solvent acetonitrile to the
      iridium(III) center and that the generally anticipated Hg(2+)-S affinity and its
      effect on the photophysical properties of iridium(III) luminophores did not play
      a role.

PMID- 22358148
TI  - Urine risk factors in children with calcium kidney stones and their siblings.
AB  - Calcium nephrolithiasis in children is increasing in prevalence and tends to be
      recurrent. Although children have a lower incidence of nephrolithiasis than
      adults, its etiology in children is less well understood; hence, treatments
      targeted for adults may not be optimal in children. To better understand
      metabolic abnormalities in stone-forming children, we compared chemical
      measurements and the crystallization properties of 24-h urine collections from
      129 stone formers matched to 105 non-stone-forming siblings and 183 normal,
      healthy children with no family history of stones, all aged 6 to 17 years. The
      principal risk factor for calcium stone formation was hypercalciuria. Stone
      formers have strikingly higher calcium excretion along with high supersaturation
      for calcium oxalate and calcium phosphate, and a reduced distance between the
      upper limit of metastability and supersaturation for calcium phosphate,
      indicating increased risk of calcium phosphate crystallization. Other differences
      in urine chemistry that exist between adult stone formers and normal individuals
      such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume
      were not found in these children. Hence, hypercalciuria and a reduction in the
      gap between calcium phosphate upper limit of metastability and supersaturation
      are crucial determinants of stone risk. This highlights the importance of
      managing hypercalciuria in children with calcium stones.

PMID- 22358150
TI  - The first total synthesis of (+)-mucosin.
AB  - The first total synthesis of (+)-mucosin has been completed allowing assignment
      of the absolute stereochemistry of the natural product. A zirconium induced co
      cyclisation was utilised to install the correct stereochemistry of the four
      contiguous stereocentres around the unusual bicyclo[4.3.0]nonene core.

PMID- 22358154
TI  - Computational prediction of ionic liquid 1-octanol/water partition coefficients.
AB  - Wet 1-octanol/water partition coefficients (log K(ow)) predicted for imidazolium
      based ionic liquids using adaptive bias force-molecular dynamics (ABF-MD)
      simulations lie in excellent agreement with experimental values. These
      encouraging results suggest prospects for this computational tool in the a priori
      prediction of log K(ow) values of ionic liquids broadly with possible screening
      implications as well (e.g., prediction of CO(2)-philic ionic liquids).

PMID- 22358155
TI  - Pill burden in HIV infection: 20 years of experience.
AB  - BACKGROUND: New antiretroviral (ARV) drugs and improved formulations and
      coformulations of existing ARVs are actively promoted to diminish a patient's
      pill burden and to minimise the opportunity for mismatched dosing, although the
      effect of these advances is poorly understood. We determine how these changes
      affect the total daily pill burden (TDPB) for ARV and other drug use over a 20
      year period. METHODS: Using our in-house pharmacy database, we calculated the
      daily number and associated pill burden of oral ARV and non-ARV (prescription and
      over-the-counter) medications taken by every patient within the Southern Alberta
      Cohort (SAC) between 1990 and 2010. We compared the mean TDPB with the patients'
      sociodemographic and clinical characteristics. RESULTS: Mean TDPB for ARV
      experienced patients increased from 4.9 in 1990 to 12.1 in 1998 but decreased to
      6.7 in 2010. By 2010, new ARVs and newer formulations had decreased ARV pill
      burden by 50% over five years. In 1990, however, 95% of the TDPB consisted of
      ARVs but by 2010 it fell to 51% as non-ARV daily drugs increased from 0.2 in 1990
      to 2.6 in 2010. Variation in TDPB was attributable to four main factors:
      patient's age, risk factor, nadir CD4(+) T-cell count and duration of known HIV
      infection. CONCLUSIONS: While new ARV formulations and coformulations have
      simplified regimens, this reduction in ARV pill burden has been counterbalanced
      by increases in non-ARV drugs required for managing comorbidities. Discussions on
      merits of coformulations in decreasing ARV pill burden need to include the non
      ARV pill burden.

PMID- 22358156
TI  - Optical image hiding with silhouette removal based on the optical interference
      principle.
AB  - The earlier proposed interference-based encryption method with two phase-only
      masks (POMs), which actually is a special case of our method, is quite simple and
      does not need iterative encoding. However, it has been found recently that the
      encryption method has security problems and cannot be directly applied to image
      encryption due to the inherent silhouette problem. Several methods based on
      chaotic encryption algorithms have been proposed to remove the problem by
      postprocessing of the POMs, which increased the computation time or led to
      digital inverse computation in decryption. Here we propose a new method for image
      encryption based on optical interference and analytical algorithm that can be
      directly used for image encryption. The information of the target image is hidden
      into three POMs, and the silhouette problem that exists in the method with two
      POMs can be resolved during the generation procedure of POMs based on the
      interference principle. Simulation results are presented to verify the validity
      of the proposed approach.

PMID- 22358157
TI  - Assessment of linear semiconductor amplifiers for upgrading WDM-PONs with
      wavelength reuse.
AB  - In this work we have assessed the capacity of a linear semiconductor optical
      amplifier to compensate the fiber and component losses present in a wavelength
      division multiplexing passive optical network (WDM-PON) evolution from fiber-to
      the-building (FTTB) to fiber-to-the-home access. The evaluation measurements
      confirm that the presence of a semiconductor optical amplifier placed at the
      entry of a group of optical network units that share the same wavelength channel
      can raise the loss budget that the link can tolerate in the fiber, compensating
      for the losses of a passive splitter up to a 1:16 division rate, allowing the
      upgrade of existing WDM-PON FTTB structures to make the fiber reach the final
      user's home.

PMID- 22358158
TI  - Holographic polymer dispersed liquid crystal enhanced by introducing urethane
      trimethacrylate.
AB  - This work characterizes holographic polymer dispersed liquid crystals (HPDLC)
      composite material based on a new monomer, urethane trimethacrylate, by
      fabricating switchable diffraction grating. The highest diffraction efficiency
      achieved was 90.3%. Details of the fabrication and preliminary results of electro
      optical switching of the HPDLC diffraction gratings are presented and discussed
      based on the functionality of the monomer. These experimental results are
      explained by means of morphological scanning electron microscopy analyses.

PMID- 22358159
TI  - Projection approach to complexity reduction in tomographic alignment of extremely
      large telescopes.
AB  - We describe a complexity reduction approach intended to solve the tomographic
      alignment problem for the Thirty Meter Telescope by means of its alignment and
      phasing system (APS) with little loss of information. This approach is
      computationally efficient enough to perform detailed Monte-Carlo simulations of
      the APS on a standard PC. We present sample simulations to model error
      propagation through the system and to build a preliminary APS alignment error
      budget.

PMID- 22358160
TI  - High-efficiency holograms fixed in lithium niobate after recording using a
      digital fringe stabilization system.
AB  - We used a digital feedback control loop system to produce reproducible fixed
      volume transmission holograms of high diffraction efficiency. Different
      strategies were investigated to obtain holograms of good quality and the highest
      refractive index modulation depth. Using this control system, we were able to
      record holograms with stationary fringes. Additionally to using the stationary
      fringe recording, a double recording-fixing schedule resulted in being the most
      appropriate one to produce reproducible holograms of better characteristics. This
      strategy is discussed and compared with other already established ones.

PMID- 22358161
TI  - Rotation angle measurement based on white-light interferometry with a standard
      optical flat.
AB  - We propose a simple white-light interferometric method of measuring a one
      dimensional rotation angle with use of an optical plane parallel plate of
      standard refractive index. The phase change of the interference pattern of the
      interferometer during the rotation of the flat plate of known refractive index
      and thickness placed in one of the interferometer's arms is used for
      determination of the rotation angle. This method has been demonstrated for an
      accurate angle measurement over the angle range from 0 degrees  to 40 degrees 
      within a maximum uncertainty of 0.057 degrees .

PMID- 22358162
TI  - Thermal-structural modeling of polymer Bragg grating waveguides illuminated by a
      light emitting diode.
AB  - This study reports both analytical and numerical thermal-structural models of
      polymer Bragg grating (PBG) waveguides illuminated by a light emitting diode
      (LED). A polymethyl methacrylate (PMMA) Bragg grating (BG) waveguide is chosen as
      an analysis vehicle to explore parametric effects of incident optical powers and
      substrate materials on the thermal-structural behavior of the BG. Analytical
      models are verified by comparing analytically predicted average excess
      temperatures, and thermally induced axial strains and stresses with numerical
      predictions. A parametric study demonstrates that the PMMA substrate induces more
      adverse effects, such as higher excess temperatures, complex axial temperature
      profiles, and greater and more complicated thermally induced strains in the BG
      compared with the Si substrate.

PMID- 22358163
TI  - Mueller matrix roots depolarization parameters.
AB  - The Mueller matrix roots decomposition recently proposed by Chipman in [1] and
      its three associated families of depolarization (amplitude depolarization, phase
      depolarization, and diagonal depolarization) are explored. Degree of polarization
      maps are used to differentiate among the three families and demonstrate the unity
      between phase and diagonal depolarization, while amplitude depolarization remains
      a distinct class. Three families of depolarization are generated via the
      averaging of different forms of two nondepolarizing Mueller matrices. The
      orientation of the resulting depolarization follows the cyclic permutations of
      the Pauli spin matrices. The depolarization forms of Mueller matrices from two
      scattering measurements are analyzed with the matrix roots decomposition-a sample
      of ground glass and a graphite and wood pencil tip.

PMID- 22358164
TI  - Quantitative security evaluation of optical encryption using hybrid phase- and
      amplitude-modulated keys.
AB  - In the increasing number of system approaches published in the field of optical
      encryption, the security level of the system is evaluated by qualitative and
      empirical methods. To quantify the security of the optical system, we propose to
      use the equivalent of the key length routinely used in algorithmic encryption. We
      provide a calculation method of the number of independent keys and deduce the
      binary key length for optical data encryption. We then investigate and optimize
      the key length of the combined phase- and amplitude-modulated key encryption in
      the holographic storage environment, which is one of the promising solutions for
      the security enhancement of single- and double-random phase-encoding encryption
      and storage systems. We show that a substantial growth of the key length can be
      achieved by optimized phase and amplitude modulation compared to phase-only
      encryption. We also provide experimental confirmation of the model results.

PMID- 22358165
TI  - Improved white-light interferometry on rough surfaces by statistically
      independent speckle patterns.
AB  - White-light interferometry (WLI) on rough surfaces is based on interference from
      individual speckles. The measurement uncertainty of WLI is limited by a random
      shift of these individual interference patterns. The statistical error in each
      measurement point depends on the brightness of the corresponding speckle: a dark
      speckle yields a larger error than a bright speckle. In this paper, a novel
      method is presented to reduce the measurement uncertainty significantly: by
      sequentially switching the direction of the illumination, the camera sees several
      independent speckle patterns in sequence. From each pattern, the brightest
      speckles are selected to eventually calculate an accurate height map. This height
      map displays no outliers, and the measured surface roughness is close to the
      stylus measurements.

PMID- 22358166
TI  - Current measurement by Faraday effect on GEPOPU.
AB  - The design of an optical current sensor to be used in a pulsed power generator is
      presented. The current sensor is based on the polarization rotation by the
      Faraday effect. GEPOPU is a pulsed power generator, 110 kA, 120 ns double transit
      time, 1.5 Omega coaxial geometry, and current rise time of 50 ns. Two different
      optical geometries surrounding the conductor were tried, using Amici roof prism
      and pentaprism to go around the current once, as a way to preserve the state of
      polarization along the optical path by means of complementary reflections within
      the sensing element. We believe this to be the first time that such large and
      rapidly varying currents have been measured with this configuration. The values
      obtained for both geometries agree with the values obtained with a Rogowski coil.
      The traces obtained are completely noise-free and no significant time lag has
      been observed between the current determined from the Faraday rotation and the
      current measured using a Rogowski coil.

PMID- 22358167
TI  - Super deep 3D images from a 3D omnifocus video camera.
AB  - When using stereographic image pairs to create three-dimensional (3D) images, a
      deep depth of field in the original scene enhances the depth perception in the 3D
      image. The omnifocus video camera has no depth of field limitations and produces
      images that are in focus throughout. By installing an attachment on the omnifocus
      video camera, real-time super deep stereoscopic pairs of video images were
      obtained. The deeper depth of field creates a larger perspective image shift,
      which makes greater demands on the binocular fusion of human vision. A means of
      reducing the perspective shift without harming the depth of field was found.

PMID- 22358168
TI  - Rangeability extension of fiber-optic low-coherence measurement based on cascaded
      multistage fiber delay line.
AB  - We demonstrate a simple method to extend the measurable fiber length with a fiber
      optic low-coherence technique. This method is based on a cascaded structure of
      multistage fiber delay line laid in one arm of the low-coherence technique. By
      choosing different individual stages in the cascaded fiber delay line, the length
      of the fiber under test can be continuously measured with a different measurement
      range. The measurement range of 0.81 km and spatial resolution of 60 MUm are
      successfully realized.

PMID- 22358169
TI  - Narrow bandpass tunable terahertz filter based on photonic crystal cavity.
AB  - We have fabricated a very narrow bandpass tunable terahertz (THz) filter based on
      a one-dimensional photonic crystal cavity. Since the filter consists of silicon
      wafers and air spacers, it has a very high quality factor of about 1500. The full
      width at half maximum (FWHM) of the passband is only about 200 MHz, and the peak
      transmission is higher than -4 dB. Besides, the central frequency can be tuned
      rapidly over the entire bandgap with the length of cavity adjusted by a motorized
      linear stage. Further analytical calculations indicate that a high-Q tunable
      filter with both high peak transmission and wide tunable range is possible if
      thinner silicon layers are used.

PMID- 22358173
TI  - Space matters.

PMID- 22358174
TI  - Three-dimensional computer-assisted navigation for the placement of cannulated
      hip screws. A pilot study.
AB  - PURPOSE: Medial femoral neck fractures are common, and closed reduction and
      internal fixation by three cannulated screws is an accepted method for the
      surgical treatment. Computer navigation for screw placement may reduce
      fluoroscopy time, the number of guidewire passes and optimise screw placement.
      METHODS: In the context of a sawbone study, a computer-assisted planning and
      navigation system based on 3D-imaging for guidewire placement in the femoral neck
      was tested to improve screw placement. Three screws were inserted into 12,
      intact, femoral sawbones using the conventional technique and into 12, intact,
      femoral sawbones guided by the computer-based navigation system. Guidewire and
      subsequent screw placement in the femoral neck were evaluated. RESULTS: Use of
      the navigation system resulted in a significant reduction of the number of
      drilling attempts (p<=0.05) and achieved optimised accuracy of implant placement
      by attaining significantly better screw parallelism (p<=0.05) and significantly
      enlarged neck-width coverage by the three screws (p<=0.0001). Computer assistance
      significantly increased the number of fluoroscopic images (p<=0.001) and the
      operation time (p<=0.0001). CONCLUSIONS: Three-dimensional computer-assisted
      navigation improves accuracy of cannulated screw placement in femoral neck while
      increasing the number of fluoroscopic images and operation time. Additional
      studies including fractured sawbones and cadaver models with the goal of reducing
      operation time are indispensable before introduction of this navigation system
      into clinical practice.

PMID- 22358175
TI  - Foot loading with an ankle-foot orthosis: the accuracy of an integrated physical
      strain trainer.
AB  - PURPOSE: To investigate the value of a built-in physical strain trainer for the
      monitoring of partial weight bearing with an ankle-foot orthosis. METHODS: 12
      healthy volunteers were asked to perform three trials. Plantar peak pressure
      values from normal gait (trial one) were defined as 100% (baseline). The
      following trials were performed with the Vacoped(r) dynamic vacuum ankle orthosis
      worn in a neutral position with full weight bearing (trial two) and a restriction
      to 10% body weight (BW) (trial three), as monitored with an integrated physical
      strain trainer. Peak plantar pressure values were obtained using the pedar(r) X
      system. RESULTS: Peak pressure values were statistically significantly reduced
      wearing the Vacoped(r) shoe with full weight bearing for the hindfoot to 68% of
      the baseline (normal gait) and for the midfoot and forefoot to 83% and 60%,
      respectively. Limited weight bearing with 10% BW as controlled by physical strain
      trainer further reduced plantar peak pressure values for the hindfoot to 19%, for
      the midfoot to 43% of the baseline and the forefoot to 22% of the baseline.
      CONCLUSIONS: The Vacoped(r) vacuum ankle orthosis significantly reduces plantar
      peak pressure. The integrated physical strain trainer seems unsuitable to monitor
      a limitation to 10% BW adequately for the total foot. The concept of controlling
      partial weight bearing with the hindfoot-addressing device within the orthosis
      seems debatable but may be useful when the hindfoot in particular must be off
      loaded.

PMID- 22358176
TI  - Characteristics of patients with spinal tuberculosis: seven-year experience of a
      teaching hospital in Southwest China.
AB  - PURPOSE: The purpose of this study was to investigate the characteristics of
      patients managed for spinal tuberculosis at the orthopaedics department of a
      teaching hospital in Chongqing, China, between 2004 and 2010. METHODS: The study
      used a retrospective chart review. The epidemiology, clinical features,
      laboratory test results, imaging study findings, and treatment methods were
      recorded. RESULTS: The annual incidence of spinal tuberculosis was stable
      throughout the study period. There were 284 patients, 147 women and 137 men, with
      a mean age of 38.2 years. The majority of the lesions involved the thoracic spine
      (45.3%), followed by the lumbar spine (45.0%). Multiple level skip lesions were
      seen in 5.6% of cases. The erythrocyte sedimentation rate was normal in 26.8% of
      patients. The C-reactive protein (CRP) was normal in 30.2% of patients. Type A
      and type O were the most common blood types. Neurological involvement was seen in
      21.8% of patients. Concomitant tuberculosis of the lung was seen in 73 (25.7%).
      The patients with middle school education and above account for 60.4% (102/169)
      in rural patients and 68.7% (79/115) in urban patients. Mean time from symptom
      onset to diagnosis was 18.0 months (range, three days to 360 months), and there
      was a significant difference between the rural patients (23.0 months) and the
      urban patients (10.7 months) (p=0.001, t=-3.300). Surgical treatment was
      performed in 233 patients (82.0%). The preferred surgical procedure was radical
      anterior debridement, bone grafting and internal fixation (132 patients, 46.5%).
      There were 13 patients (4.2%) with anti-tuberculous chemotherapy drug allergy or
      toxicity, streptomycin anaphylaxis and toxicity in 12, and isoniazide anaphylaxis
      and toxicity in one. No mortality was related to spinal TB. CONCLUSION: The
      annual incidence of spinal tuberculosis remained unchanged throughout the study
      period and most of the patients did not pay much attention to the disease and
      received timely treatment. Thus, we should strengthen the census and treatment of
      spinal tuberculosis in Southwest China.

PMID- 22358177
TI  - Recent advances in transition-metal catalyzed reactions using molecular oxygen as
      the oxidant.
AB  - For green and sustainable chemistry, molecular oxygen is considered as an ideal
      oxidant due to its natural, inexpensive, and environmentally friendly
      characteristics, and therefore offers attractive academic and industrial
      prospects. This critical review introduces the recent advances over the past 5
      years in transition-metal catalyzed reactions using molecular oxygen as the
      oxidant. This review highlights the scope and limitations, as well as the
      mechanisms of these oxidation reactions (184 references).

PMID- 22358178
TI  - Confocal ultrafast pump-probe spectroscopy: a new technique to explore nanoscale
      composites.
AB  - This article is devoted to the exploration of the benefits of a new ultrafast
      confocal pump-probe technique, able to study the photophysics of different
      structured materials with nanoscale resolution. This tool offers many advantages
      over standard stationary microscopy techniques because it directly interrogates
      excited state dynamics in molecules, providing access to both radiative and non
      radiative deactivation processes at a local scale. In this paper we present a few
      different examples of its application to organic semiconductor systems. The first
      two are focussed on the study of the photophysics of phase-separated polymer
      blends: (i) a blue-emitting polyfluorene (PFO) in an inert matrix of PMMA and
      (ii) an electron donor polythiophene (P3HT) mixed with an electron acceptor
      fullerene derivative (PCBM). The experimental results on these samples
      demonstrate the capability of the technique to unveil peculiar interfacial
      dynamics at the border region between phase-segregated domains, which would be
      otherwise averaged out using conventional pump-probe spectroscopy. The third
      example is the study of the photophysics of isolated mesoscopic crystals of the
      PCBM molecule. Our ultrafast microscope could evidence the presence of two
      distinctive regions within the crystals. In particular, we could pinpoint for the
      first time areas within the crystals showing photobleaching/stimulated emission
      signals from a charge-transfer state.

PMID- 22358179
TI  - Approximately size extensive local Multireference Singles and Doubles
      Configuration Interaction.
AB  - Multi-reference Configuration Interaction (MRCI) is often used to predict the
      electronic structures and reaction energetics of small molecules with very high
      accuracy. Unfortunately, MRCI is inapplicable to large or even medium-sized
      molecules for two reasons: its computational cost scales poorly with molecule
      size and MRCI methods are not size extensive, leading to large energy errors. We
      have developed a new local (L) and approximately size extensive MRCI method that
      addresses both shortcomings. Truncating long-range electron correlation in a
      local orbital basis as well as efficient processing of two-electron integrals via
      Cholesky decomposition (CD) and integral screening reduce the computational cost
      to O(N(3)) with a small prefactor. A priori and a posteriori size extensivity
      corrections are both considered. The Multi-reference Averaged Coupled-Pair
      Functional (MRACPF) provides approximate size extensivity by modifying the energy
      functional. The very inexpensive Davidson-Silver and Pople a posteriori schemes
      also produce quite accurate corrections over a large range of molecular size.
      Employing CD-LMRACPF is slightly more expensive than using a Davidson-type
      correction, but the former gives superior results. Molecules with up to 50 heavy
      atoms can be treated with our CD-LMRACPF method thus far.

PMID- 22358180
TI  - The times have changed: molecular pathology is here to stay. A commentary on:
      analytical performance of a PCR assay for the detection of KRAS mutations (codons
      12/13 and 61) in formalin-fixed paraffin-embedded tissue samples of colorectal
      carcinoma, by Lee et al. In this issue.

PMID- 22358181
TI  - Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary
      organs.
AB  - Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases
      of mixed adenoneuroendocrine carcinoma (MANEC) have been reported. In this study,
      we characterized the neuroendocrine component of biliary MANEC. A total of 274
      cases of biliary cancer including 17 intrahepatic cholangiocarcinomas (CCs), 15
      hepatic hilar CCs without preceding hepatobiliary disease, 55 hepatic hilar CCs
      with hepatolithiasis, 49 gallbladder cancers, 53 extrahepatic CCs, and 85
      hepatocellular carcinomas were examined for a neuroendocrine component using
      immunohistochemistry with neuroendocrine markers (chromogranin A and
      synaptophysin). In the MANEC cases, in addition to a close histological
      examination, the proliferative activity and the expression of somatostatin
      receptor 2A were also evaluated. In addition to an ordinary adenocarcinoma, a
      neuroendocrine component occupying more than 30% of the entire tumor was also
      found in 4% (2/55 cases) of hepatic hilar cholangiocarcinomas with
      hepatolithiasis, 10% (5/49 cases) of gallbladder cancers, and 4% (2/53 cases) of
      extrahepatic cholangiocarcinomas, but not in the intrahepatic
      cholangiocarcinomas, hilar cholangiocarcinomas without preceding hepatobiliary
      disease, and hepatocellular carcinomas. Two cases were positive for somatostatin
      receptor 2A. The adenocarcinoma components were predominately located at the
      surface of the tumors, and the majority of stromal and vascular invasion and
      lymph node metastasis involved neuroendocrine components, showing the features of
      neuroendocrine tumor G2 or neuroendocrine carcinomas (NECs). NEC components
      showed higher proliferative activity on Ki67 immunostaining, compared to the
      adenocarcinoma components. Biliary MANECs are found in hepatic hilar
      cholangiocarcinomas with hepatolithiasis, gallbladder cancers, and extrahepatic
      cholangiocarcinomas and show a characteristic histology. Since the neuroendocrine
      component in biliary MANEC defines the prognosis, it is important to identify it
      and consider the indications for adjunctive therapy with somatostatin analogues.

PMID- 22358182
TI  - Effect of time on colony odour stability in the ant Formica exsecta.
AB  - Among social insects, maintaining a distinct colony profile allows individuals to
      distinguish easily between nest mates and non-nest mates. In ants, colony
      specific profiles can be encoded within their cuticular hydrocarbons, and these
      are influenced by both environmental and genetic factors. Using nine monogynous
      Formica exsecta ant colonies, we studied the stability of their colony-specific
      profiles at eight time points over a 4-year period. We found no significant
      directional change in any colony profile, suggesting that genetic factors are
      maintaining this stability. However, there were significant short-term effects of
      season that affected all colony profiles in the same direction. Despite these
      temporal changes, no significant change in the profile variation within colonies
      was detected: each colony's profile responded in similar manner between seasons,
      with nest mates maintaining closely similar profiles, distinct from other
      colonies. These findings imply that genetic factors may help maintain the long
      term stability of colony profile, but environmental factors can influence the
      profiles over shorter time periods. However, environmental factors do not
      contribute significantly to the maintenance of diversity among colonies, since
      all colonies were affected in a similar way.

PMID- 22358183
TI  - Transmetalation of a nucleophilic carbene fragment: from early to late transition
      metals.
AB  - Early transition metal nucleophilic carbene complexes have been used as
      stoichiometric carbene transfer agents in a transmetalation process.

PMID- 22358184
TI  - Microfluidic system for simultaneous optical measurement of platelet aggregation
      at multiple shear rates in whole blood.
AB  - Thrombosis is the pathological formation of platelet aggregates which occlude
      blood flow causing stroke and heart attack-the leading causes of death in
      developed nations. Instrumentation for diagnosing and exploring treatments for
      pathological platelet aggregation thus has the potential for major clinical
      impact. Most current thrombosis methods focus on single flow conditions, non
      occlusive platelet adhesion, or low shear rates and so are limited in their
      application to comparative studies involving multiple, pathological test
      conditions (e.g., shear rate, stenotic geometries that mimic arteries, and rapid
      platelet accumulation to occlusion). The field could benefit from a low volume,
      high throughput, short analysis time, and low cost system while minimizing sample
      handling. We report on the design, fabrication, testing, and application of a
      microfluidic device and associated optical system for simultaneous measurement of
      platelet aggregation at multiple initial shear rates within four stenotic
      channels in label-free whole blood. Following computational design, requisite
      shear rates were achieved in the device by micro- surface milling a mold and
      subsequent PDMS casting. We applied the microfluidic system to measure platelet
      aggregation in whole porcine blood for shear rates spanning physiological to
      pathological flow conditions (500-13000 s(-1)). Real-time, non-contact, label
      free, microscope-free measurements of platelet aggregation were acquired using an
      optical system comprising a 650 nm diode laser and a linear CCD. We observed
      fully occlusive platelet aggregation in less than 20 min above a threshold
      initial shear rate of 4000 s(-1), and no occlusive platelet aggregation below
      1500 s(-1) (N = 86 trials). Accumulation of thrombus was consistent between laser
      intensity, light microscopy, histology, and mass flow rate measurements. The
      amount of blood volumes producing occlusion were dependent on shear rate. Times
      to occlusion were not found to be dependent on shear rate above the threshold
      level of 4000 s(-1). This microfluidic system enables measurement of the entire
      process of occlusive platelet thrombosis in whole, unlabeled blood, in vitro, at
      multiple shear rates. Such a system may be useful as a point-of-care diagnostic
      tool for studying anti-platelet therapies in individual blood samples from high
      risk patients.

PMID- 22358186
TI  - Water-soluble Fe3O4 nanoparticles with high solubility for removal of heavy-metal
      ions from waste water.
AB  - In this contribution, we synthesized water-soluble Fe(3)O(4) nanoparticles (NPs)
      with sufficiently high solubility (28 mg mL(-1)) and stability (at least one
      month) through a hydrothermal approach, and found that they exhibited excellent
      removal ability for heavy-metal ions from waste water. For the first time, the
      water-soluble Fe(3)O(4) NPs were used as adsorbents for heavy-metals removal from
      wastewater. It is noteworthy that the adsorption ability of the water-soluble
      Fe(3)O(4) NPs for Pb(2+) and Cr(6+) is stronger than water-insoluble Fe(3)O(4)
      NPs. Furthermore, the water-soluble Fe(3)O(4) NPs exhibited relatively high
      saturation magnetization (83.4 emu g(-1)), which allowed their highly-efficient
      magnetic separation from wastewater. The most important thing is that the water
      soluble magnetite as an adsorbent can directly dissolve in water without the help
      of mechanical stirring or any extraneous forces, which may solve a key problem
      for the practical application of magnetic powders in the field of sewage
      purification. Moreover, the water-soluble Fe(3)O(4) NPs show a highly-efficient
      adsorption capacity for 10 ppm of Pb(2+) ions solution which can reach 90% within
      2 minutes.

PMID- 22358185
TI  - In silico cloning and characterization of the glycerol-3-phosphate dehydrogenase
      (GPDH) gene family in the green microalga Chlamydomonas reinhardtii.
AB  - Glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the conversion of
      dihydroxyacetone phosphate (DHAP) and NADH to glycerol-3-phosphate (G3P) and
      NAD(+). G3P is important as a precursor for glycerol and glycerolipid synthesis
      in microalgae. A GPDH enzyme has been previously purified from the green
      microalga Chlamydomonas reinhardtii, however, no genes coding for GPDH have been
      characterized before. In this study, we report the in silico characterization of
      three putative GPDH genes from C. reinhardtii: CrGPDH1, CrGPDH2, and CrGPDH3.
      These sequences showed a significant similarity to characterized GPDH genes from
      the microalgae Dunaliella salina and Dunaliella viridis. The prediction of the
      three-dimensional structure of the proteins showed the characteristic fold
      topology of GPDH enzymes. Furthermore, the phylogenetic analysis showed that the
      three CrGPDHs share the same clade with characterized GPDHs from Dunaliella
      suggesting a common evolutionary origin and a similar catalytic function. In
      addition, the K(a)/K(s) ratios of these sequences suggested that they are under
      purifying selection. Moreover, the expression analysis showed a constitutive
      expression of CrGPDH1, while CrGPDH2 and CrGPDH3 were induced in response to
      osmotic stress, suggesting a possible role for these two sequences in the
      synthesis of glycerol as a compatible solute in osmoregulation, and perhaps also
      in lipid synthesis in C. reinhardtii. This study has provided a foundation for
      further biochemical and genetic studies of the GPDH family in this model
      microalga, and also opportunities to assess the potential of these genes to
      enhance the synthesis of TAGs for biodiesel production.

PMID- 22358187
TI  - Temperature dependence of charge mobility in model discotic liquid crystals.
AB  - We address the calculation of charge carrier mobility of liquid-crystalline
      columnar semiconductors, a very promising class of materials in the field of
      organic electronics. We employ a simple coarse-grained theoretical approach and
      study in particular the temperature dependence of the mobility of the well-known
      triphenylene family of compounds, combining a molecular-level simulation for
      reproducing the structural changes and the Miller-Abrahams model for the
      evaluation of the transfer rates within the hopping regime. The effects of
      electric field, positional and energetic disorder are also considered.
      Simulations predict a low energetic disorder (~0.05 eV), slightly decreasing with
      temperature within the crystal, columnar and isotropic phases, and fluctuations
      of the square transfer integral of the order of 0.003 eV(2). The shape of the
      temperature-dependent mobility curve is however dominated by the variation of the
      transfer integral and barely affected by the disorder. Overall, this model
      reproduces semi-quantitatively all the features of experimentally measured
      mobilities, on one hand reinforcing the correctness of the hopping transport
      picture and of its interplay with system morphology, and on the other suggesting
      future applications for off-lattice modeling of organic electronics devices.

PMID- 22358189
TI  - Syndrome of inappropriate antidiuresis and cerebral salt wasting syndrome: are
      they different and does it matter?
AB  - The syndrome of inappropriate antidiudresis (SIAD) and cerebral salt wasting
      (CSW) are similar conditions with the main difference being the absence or
      presence of volume depletion. The two conditions may be indistinguishable at
      presentation, as volume status is difficult to assess, which can lead to under
      diagnosis of CSW in patients with central nervous system (CNS) disease. Carefully
      conducted studies in patients with CNS disease have indicated that CSW may be
      more common than SIAD. CSW may be differentiated from SIAD based on the
      persistence of hypouricemia and increased fractional excretion of urate following
      the correction of hyponatremia. Hyponatremia should be prevented if possible and
      treated promptly when discovered in patients with CNS disease as even mild
      hyponatremia could lead to neurological deterioration. Fluid restriction should
      not be used for the prevention or treatment of hyponatremia in hospitalized
      patients with CNS disease as it could lead to volume depletion especially if CSW
      is present. 0.9% sodium chloride may not be sufficiently hypertonic for the
      prevention of hyponatremia in hospitalized patients with CNS disease and a more
      hypertonic fluid may be required. The preferred therapy for the treatment of
      hyponatremia in patients with CNS disease is 3% sodium chloride.

PMID- 22358188
TI  - The role of genetics in drug dosing.
AB  - Renal transplantation is the optimal form of renal replacement therapy (RRT) for
      the majority of patients. Both short- and long-term graft rejection are well
      recognized complications following transplantation, and optimal immunosuppression
      is often difficult to achieve. Pharmacodynamics (PD) and pharmacokinetics (PK)
      are hard to predict in all patients, and best practice involves the use of
      standard dosing based on weight and therapeutic drug monitoring (TDM).
      Pharmacogenetics (PG) is the use of genetic screening to predict metabolic
      responses to different immunosuppressive drugs and enables more accurate
      predictions of PD and PK to be made. This has the potential to improve graft
      outcome by reducing both short- and long-term graft rejection.

PMID- 22358190
TI  - Serious and early-onset of hyponatremia in severe asphyctic newborns: questions.

PMID- 22358194
TI  - Neutralizing hospital-acquired infections.

PMID- 22358195
TI  - Tricking rats into liking cats.

PMID- 22358192
TI  - Early cardiac dysfunction in pediatric patients on maintenance dialysis and post
      kidney transplant.
AB  - BACKGROUND: Children with advanced chronic kidney disease (CKD) frequently
      develop left ventricular (LV) hypertrophy. The extent of hypertrophy that results
      in cardiac dysfunction is unknown. Systolic function, routinely determined by
      ejection fraction (EF), is usually preserved in these patients. However, a
      decrease in EF represents an advanced cardiac dysfunction. We used cardiac
      magnetic resonance (CMR) and phosphorus-31 MR spectroscopy (31P MRS) to assess
      markers of cardiac dysfunction in young CKD patients. METHODS: Ten dialysis and
      ten post-transplant patients completed the study. The outcomes were peak LV
      myocardial circumferential strain (Ecc); myocardial T2 relaxation time and full
      width at half maximum (FWHM) of T2 distribution; and phosphocreatinine/adenosine
      triphosphate (PCr/ATP) to measure muscle energy metabolism. Healthy controls were
      used for comparison. RESULTS: All patients had normal EF; nine (45%) had low Ecc.
      Ecc was lower in dialysis versus transplant (p<0.0001) patients and inversely
      correlated with LV mass index, r= -0.47, p=0.04. Patients had higher T2 (p=0.056)
      and FWHM (p=0.01) than controls. T2 levels were positively correlated with LVM
      index (r=0.46, p=0.04). PCr/ATP was lower in patients than in controls (p=0.02).
      CONCLUSION: Young patients with advanced CKD and normal EF have early cardiac
      changes. Association of these abnormalities with increased left ventricular mass
      (LVM) index suggests development of maladaptive hypertrophy.

PMID- 22358196
TI  - Stressed partners shorten lives of their mates.

PMID- 22358197
TI  - Saffron offers protection from liver cancer.

PMID- 22358200
TI  - Managing a pending IBC approval.

PMID- 22358201
TI  - Managing a pending IBC approval. Communicate with the PI.

PMID- 22358202
TI  - Managing a pending IBC approval. PI must wait.

PMID- 22358203
TI  - Managing a pending IBC approval. IBC approval not substantive.

PMID- 22358204
TI  - Managing a pending IBC approval. A word from OLAW and USDA.

PMID- 22358205
TI  - Soft thoracic subcutaneous mass in a rabbit (Oryctolagus cuniculus).

PMID- 22358207
TI  - Implementation of a PCR assay of Pasteurella pneumotropica to accurately screen
      for contaminated laboratory mice.
AB  - The authors implemented a PCR protocol to rapidly screen for Pasteurella
      pneumotropica and to accurately identify contaminated laboratory mice in a
      clinical setting. This protocol was implemented in response to a severe outbreak
      of P. pneumotropica in their animal facility. Although a sentinel program was in
      place to routinely screen for P. pneumotropica, it was inadequate for the
      identification of contaminated animals. As a result, several additional strains
      of mice were contaminated and developed clinical signs of infection. The authors
      implemented a screening method using PCR with reported primer pairs previously
      developed to identify the biotype isolates of P. pneumotropica in laboratory
      mice. Throat culture swabs were collected from live mice and placed in a
      bacterial culture. The DNA from these cultures was isolated and screened by PCR.
      This procedure enabled the authors to eliminate P. pneumotropica from several
      animal housing rooms. The assay can be easily applied in most animal facilities.

PMID- 22358209
TI  - The use of animals in live-tissue trauma training and military medical research.
AB  - Uncontrolled hemorrhage is the most common preventable cause of death for
      soldiers wounded in combat. In live-tissue trauma training (LTTT), animals
      (mostly goats and pigs) are used to train physicians and paramedical personnel in
      how to treat severe traumatic injuries, including severe blood loss. Military
      personnel insist that such realistic training is necessary and has to date saved
      countless lives of soldiers. Animal rights groups, however, argue that the
      practice is inhumane and should be replaced with alternative methods. In this
      essay, the author explains how and why animals are used for LTTT and in military
      medical research (MMR), as well as why he feels that the continued use of animals
      for LTTT and MMR is justified. The author hopes to encourage wider discussion of
      this topic within the scientific, defense and animal welfare circles, leading to
      further refinements in the welfare and protection of animals used for these
      important, though often controversial, purposes.

PMID- 22358208
TI  - Comparison of hypothalamic mRNA levels in mice euthanized by CO2 inhalation and
      focused-beam microwave irradiation.
AB  - Focused-beam microwave irradiation (FBMI) is a relatively new method for
      euthanasia of small mammals and is available to most researchers. Compared with
      CO2 inhalation, this method of euthanasia has the advantage of preserving fast
      degrading metabolites. But differences in brain RNA quantity and quality, gene
      expression and histology in mice euthanized by CO2 inhalation versus FBMI have
      not been investigated. Here the authors report that a smaller quantity of RNA was
      isolated from brains of mice euthanized by FBMI compared with those of mice
      euthanized by CO2 inhalation. They also found relative differences in the levels
      of the expression of some genes. These studies suggest that either method can be
      used for histological analysis or RNA isolation, but the authors caution against
      combining the techniques within a single study on gene expression.

PMID- 22358210
TI  - Managing an animal care program.

PMID- 22358212
TI  - Historical evolution of the Brazilian Annals of Dermatology.
AB  - In this special edition in celebration of the centennial of the Brazilian Society
      of Dermatology, the authors take a retrospective look at printed Brazilian
      dermatology from the very beginning onward, showing evidence of descriptive
      dermatology with rich discussions, illustrations and advertisements of
      medications much used at the time, such as bismuth for the treatment of syphilis,
      before the discovery of penicillin. This retrospective covers up to the current
      days, when publications in the Brazilian Annals of Dermatology have reached the
      modern era in electronics, science and layout as well.

PMID- 22358213
TI  - [Efficacy, tolerability and safety of paliperidone extended-release in the
      treatment of schizophrenia and schizoaffective disorder].
AB  - INTRODUCTION: The paper represents a systematic review on the efficacy,
      tolerability and safety of paliperidone, an antipsychotic drug recently approved
      in Italy for the treatment of schizophrenia and of schizoaffective disorder.
      METHODS: A comprehensive PubMed search using the term "paliperidone" was
      performed from January 1980 to February 2011. Papers reporting data on efficacy
      in the treatment of schizophrenia and of schizoaffective disorder were included,
      also if published as abstracts and all retrieved articles were manually searched
      for other references of interest. RESULTS: Paliperidone was found to be effective
      in short and long-term treatment of schizophrenia, as well as in the treatment of
      schizoaffective disorder. For both disorders, paliperidone showed to be effective
      in improving psychotic and affective symptoms. In the studies analyzed it was
      well tolerated and the most frequent reported adverse events were mild
      extrapyramidal symptoms and an increase in serum prolactin levels. CONCLUSIONS:
      Paliperidone has been shown to be an effective and safe medication for the
      treatment of schizophrenia and schizoaffective disorder. Further controlled
      clinical trials are needed to confirm this clinical profile in the long-term
      treatment, as well as for specific conditions such as schizophrenic patients with
      medical comorbidities.

PMID- 22358214
TI  - [Randomized trials, systematic reviews, meta-analyses: basic criteria in the
      world of scientific evidence].
AB  - Under ordinary circumstances choosing the best treatment for each individual
      patient is a challenging issue. This choice should be based on three main
      aspects: the patients' psychopathological status, the clinical experience and the
      best scientific knowledge available regarding efficacy and safety of each
      treatment. The approach that integrates these three aspects is known as Evidence
      Based Medicine (EBM). The aim of this report is to present the main
      methodological features of what constitutes an evidence base, in order to assist
      mental health professionals in the compelling world of scientific evidence. We
      describe randomized controlled trials as a tool for evaluating the efficacy and
      tolerability of treatments, systematic reviews of randomized trials, and meta
      analysis, a statistical technique that allows to calculate a weighted pooled
      estimate of treatment efficacy and tolerability. Finally we will describe two
      standardized tools for assessing quality of evidence, the CONSORT (Consolidated
      Standards for Reporting of Trials) statement and the GRADE (Grading of
      Recommendations Assessment, Development and Evaluation).

PMID- 22358216
TI  - The Elementary Pragmatic Model: a new perspective in psychotherapy.
AB  - This article describes the Elementary Pragmatic Model (EPM), that focuses on the
      interactions and changes that can occur between two parties. The model has
      undergone experimentation using the "Synthesis and Scission Sentences" procedure
      (SISCI Sentences) described in this work. To develop a new psychotherapy method
      firstly it was assessed whether the SISCI Sentences revealed differences between
      normal and disturbed subjects, and then whether some sentences derived from the
      SISCI procedure - using a specific automated program - really do have an impact
      even on non clinical subjects. Finally, we report some examples of clinical use
      of the sentences obtained with the described procedure.

PMID- 22358215
TI  - [Pharmaceutical formulations and adherence to pharmacological treatment  in
      psychiatry: the example of oral disintegrating tablet of olanzapine].
AB  - Adherence to treatment in psychiatric as in other chronic or recurrent
      conditions, is often suboptimal. A high proportion of relapses is due to non
      adherence to prescribed treatment. Adherence to treatment is a potent predictor
      of effectiveness, both in clinical trials and cohort studies, therefore is a very
      relevant area where any improving tool is looked forward. Orally Disintegrating
      Tablets (ODT) were developed with the aim to improve patient's compliance due to
      their fast oral absorption. They are particularly useful in psychiatric patients
      who often simulate drug assumption or experience difficulties in taking pills.
      ODT formulations have been developed for many antypsychotics including
      olanzapine. The ODT formulations of olanzapine show to be significantly different
      one from the other in the dissolution time, thus having a potential impact on
      compliance. In this review, the results of different studies consistently
      highlight the positive risk/benefit profile, the contribution to patient's
      compliance and their preference while using ODT formulation of olanzapine
      produced throughout the ZYDIS technology (Velotab). Moreover, the differences
      between olanzapine ODT (Velotab) and the standard formulation of olanzapine and
      other antipsychotics are described focusing on in efficacy, safety, patient
      acceptance and health economic impact. The ODT formulation of olanzapine
      (Velotab) seems to ameliorate patient's adherence thus improving
      psychiatrist/caregiver/patient alliance.

PMID- 22358217
TI  - [Italian validation of Multiple Visual Analogue Scales for Bipolarity (MVAS-BP)
      of Ahearn and Carroll].
AB  - AIM: The aim of the present study was to validate the Italian version and to
      assess the clinimetric properties of Ahearn and Carroll's Visual Analogue Scales
      for Bipolarity (MVAS-BP), a self-rating questionnaire measuring affective state.
      METHOD: MVAS-BP consist of 26 items: 1 item assesses overall mood, 2 items anger
      and 23 items are based on the Carroll model of bipolar disorder (Consummatory
      Reward, Incentive Reward, Central Pain, Psychomotor Regulation). MVAS-BP have
      been translated into Italian and administered with Kellner's Symptom
      Questionnaire (SQ), Ryff's Psychological Well-Being Scales (PWB), and Cloninger's
      Tridimensional Personality Questionnaire (TPQ) to a normative sample of 450
      people. The assessment was repeated after one month. Test-retest reliability,
      means scores, differences according to sociodemographic variables and
      correlations among the scales of MVAS-BP, SQ, PWB and TPQ were performed in order
      to assess clinimetric properties. RESULTS: Test-retest coefficients were highly
      significant. Significant sex differences were found in the scales of consummatory
      reward, central pain, psychomotor regulation and anger. MVAS-BP scales were
      significantly related with symptom and well-being scales, but with very low
      correlation coefficients, and only with one personality dimension, TPQ Harm
      Avoidance. DISCUSSION: MVAS-BP has been found to possess clinimetric properties
      and to record specific and different information from those investigated by other
      questionnaires.

PMID- 22358218
TI  - [Psychological distress and post-traumatic stress disorder (PTSD)  in young
      survivors of L'Aquila earthquake].
AB  - AIM: The aim of the study is to evaluate the presence of PTSD diagnosis,
      psychological distress and post-traumatic symptoms in a population of young
      earthquake survivors after L'Aquila earthquake. METHODS: Between April 2009 and
      January 2010, 187 young people seeking help consecutively at the Service for
      Monitoring and early Intervention against psychoLogical and mEntal suffering in
      young people (SMILE) of L'Aquila University Psychiatric Department, underwent
      clinical interview with the Semi-Structured Clinical Interview DSM-IV-I and-II
      (SCID-I and SCID-II) and psychometric evaluation with Impact Event Scale-Revised
      (IES-R) and General Health Questionnaire-12 items (GHQ-12). RESULTS: 44.2% and
      37.4% respectively, showed high and moderate levels of psychological distress.
      66.7% reported the presence of a significant post-traumatic symptoms (Post
      traumatic Syndrome) with an IES-R>28, while a diagnosis of PTSD was made in 13.8%
      of the sample. The obsessive-compulsive trait, female sex and high level of
      distress (GHQ >=20) appear to be the main risk factors for the development of
      PTSD than those who had a post-traumatic syndrome for which the displacement and
      social disruption, appear to be more associated with post-traumatic aftermaths.
      DISCUSSION: Our findings, in line with recent literature, confirm that a natural
      disaster produces an high psychological distress with long-term aftermaths. Early
      intervention for survivors of collective or individual trauma, regardless of the
      presence of a PTSD diagnosis should be a primary goal in a program of Public
      Health.

PMID- 22358219
TI  - [Stalking: old behaviour new crime. Reflections on 11 cases assessed in the
      judicial district of Bari].
AB  - Specific definitions aside, the behaviours that are generally associated with
      stalking may be classified into three categories of acts: 1) following (including
      showing up at the victim's home and workplace, maintaining surveillance, and
      setting up coincidences); 2) communicating (by telephone, mail, leaving notes,
      graffiti, gifts, e-mail, and internet); including the ordering of goods and
      services in the victim's name; 3) attacking or committing acts of violence
      (threats, direct harassment of the victim or of people close to the victim,
      damaging of personal goods, false accusations, physical or sexual violence). The
      work here presented proposes to find empirical confirmation of the data cited in
      the scientific literature with particular attention paid to the studies carried
      out by Mullen, Pathe, Purcell and Meloy who proposed a criminological diagnostic
      category for stalkers, delineating their behaviors . We go on to highlight
      patterns of behavior, as well as physical and social characteristics as
      postulated by these authors, and found in the molesters investigated in this
      study.

PMID- 22358220
TI  - Can the performance of graphene nanosheets for lithium storage in Li-ion
      batteries be predicted?
AB  - Graphene nanosheets (GNS) were prepared from graphitic oxide (GO) in two
      different ways: (a) thermal exfoliation at different temperatures; and (b) wet
      chemistry, using aqueous N(2)H(4) and KBH(4) as reducing agents. Irrespective of
      the synthetic method used, the materials exhibited a high irreversible capacity
      and strong polarization in their charge curves, when used in a Li-ion battery.
      The GNS synthesized with N(2)H(4) exhibited the best performance. Thus, at 149 mA
      g(-1) the average specific capacity delivered was ca. 600 mA h g(-1) after 100
      cycles. On the other hand, the worst performance, irrespective of rate, was that
      of GNS synthesized with KBH(4) and the thermal GNS obtained at 800  degrees C.
      The physical and chemical analyses allowed various parameters to be derived for
      correlation with the electrochemical properties. Unfortunately, no clear-cut
      correlation was apparent. A comparison with reported data revealed that no
      correlation appears to exist with physical and chemical properties that allows a
      simple strategy for tailoring an effective graphene anode to be designed.

PMID- 22358221
TI  - The epidemiology of knee injuries in children and adolescents.
AB  - BACKGROUND: Injuries in childhood and adolescence are frequent and the knee is
      one of the most common sites of injuries. This study aimed to analyze the
      epidemiology, gender distribution, age, and circumstances of knee injuries in
      childhood at a Level I Trauma Center in Austria. METHODS: All pediatric and
      adolescent trauma patients who presented in a 2-year period were recorded.
      Children managed with knee injuries were selected prospectively. Patients were
      divided into five age groups: infants (younger than 1 year); pre-school aged
      children (1-6 years); pre-pubertal school-aged children (7-10 years); early
      adolescent patients (11-14 years); and late adolescent patients (15-18 years).
      Five diagnosis-related groups were formed: extraarticular soft tissue injuries,
      intraarticular soft tissue injuries, patella disorders, fractures, and overload
      injuries. RESULTS: The study included 23,832 patients up to the age of 18 years,
      who presented with 1,199 knee injuries. There was a male predominance (m:f =
      58,6%:41.4%). Boys had a lower mean age at presentation (11.9 years) as girls
      (12.3 years). The most common accident sites were outdoors (34.8%) and sports
      facilities (32.8%). Leading injury mechanisms were falls on level surfaces
      (58.1%) and traffic accidents (13.4%). The number of knee injuries and its
      severity increased with age. Knee injuries did not occur in infants. In general,
      extraarticular soft-tissue injuries were most common and fractures were rare.
      CONCLUSION: Knee injuries in children and adolescents are rare and extraarticular
      soft-tissue injury is the most frequent type of knee trauma. The number of knee
      injuries and its severity increases with age with a male predominance. Sports
      facilities and traffic injuries are important scenes of knee trauma. Mechanisms
      and patterns evaluated in this study can serve as the basis for knee-injury
      prevention efforts in children and adolescents and may be used for necessary
      precautions. LEVEL OF EVIDENCE: IV.

PMID- 22358222
TI  - Percutaneous fixation of acetabular fractures: computer-assisted determination of
      safe zones, angles and lengths for screw insertion.
AB  - INTRODUCTION: Percutaneous retrograde screw fixation for acetabular fractures is
      a demanding procedure due to the complex anatomy of the pelvis and the varying
      narrow safe bony corridors. Limited information is available on optimal screw
      placement and the geometry of safe zones for screw insertion in the pelvis.
      METHODS: Three-dimensional reconstructions of 50 consecutive CT scans of
      polytrauma patients (35 males, 15 females) were used to introduce three virtual
      CAD bolts (representing screws) into the anterior column (superior ramus of the
      pubic bone), posterior column (the ischial bone) and the supraacetabular region,
      as performed during percutaneous screw fixation. The three-dimensional (3D)
      position of these screws was evaluated with a computer software (MIMICS) after
      virtual optimal insertion. The 3D position, the narrowest zone and the distance
      to the hip joint of the two columns and the supraacetabular region were defined.
      RESULTS: The mean maximal screw length for the three virtual screws measured
      between 107.4 and 148 +/- 18.7 mm. The narrowest zone of the pelvic bone
      (superior pubic ramus) had a width of 9.2 +/- 2.4 mm. The average distances
      between the bolts and the hip joint were 3.9 and 19.4 +/- 7.4 mm. For the
      anterior column (superior pubic ramus) screw, the mean lateral angle to the
      sagittal midline plane was 39.0 +/- 3.2 degrees  and the mean posterior angle to
      the transversal midline plane was 15.1 +/- 4.0 degrees . The mean supraacetabular
      screw angles measured 22.4 +/- 3.4 degrees  (medial), 35.3 +/- 4.6 degrees 
      (cranial) and the mean angles for the ischial screw were 12.0 +/- 5.4 degrees 
      (posterior) and 18.4 +/- 4.0 degrees  (lateral). CONCLUSIONS: The zones for safe
      screw positioning are very narrow, making percutaneous screw fixation of the
      acetabulum a challenging procedure. The predefined angles for the most frequently
      positioned percutaneous screws may aid in preoperative planning, decrease
      operative and radiation times and help to increase safe insertion of screws.

PMID- 22358223
TI  - Phosphoramidate prodrugs of (-)-beta-D-(2R,4R)-dioxolane-thymine (DOT) as potent
      anti-HIV agents.
AB  - BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) are an effective
      class of agents that has played a vital role in the treatment of HIV infections.
      (-)-beta-D-(2R,4R)-dioxolane-thymine (DOT) is a thymidine analogue that is active
      against wild-type and NRTI-resistant HIV-1 mutants. It has been shown that the
      anti-HIV activity of DOT is limited due to poor monophosphorylation. METHODS: To
      further enhance the anti-HIV activity of DOT, an extensive structure-activity
      relationship analysis of phosphoramidate prodrugs of DOT monophosphate was
      undertaken. These prodrugs were evaluated for anti-HIV activity using Hela CD4
      beta-gal reporter cells (P4-CCR5 luc cells). RESULTS: Among the synthesized
      prodrugs, the 4-bromophenyl benzyloxy l-alanyl phosphate derivative of DOT was
      the most potent, with a 50% effective concentration of 0.089 MUM corresponding to
      a 75-fold increase in activity relative to the parent nucleoside DOT with no
      increased cytotoxicity. The metabolic stability of a selected number of potent
      DOT phosphoramidates was also evaluated in simulated gastric fluid, simulated
      intestinal fluid, human plasma and liver S9 fractions. CONCLUSIONS: A series of
      new phosphoramidate prodrugs of DOT were prepared and evaluated as inhibitors of
      HIV replication in vitro. Metabolic stability studies indicated that these DOT
      phosphoramidate derivatives have the potential to show acceptable stability in
      the gastrointestinal tract, but they metabolize rapidly in the liver.

PMID- 22358224
TI  - Quantitative measurement of quantum dot uptake at the cell population level using
      microfluidic evanescent-wave-based flow cytometry.
AB  - The intracellular uptake of nanoparticles (NPs) is an important process for
      molecular and cellular labeling, drug/gene delivery and medical imaging. The vast
      majority of investigations into NP uptake have been conducted using confocal
      imaging that is limited to observation of a small number of cells. Such data may
      not yield quantitative information about the cell population due to the tiny
      sample size and the potential heterogeneity. Flow cytometry is the technique of
      choice for studying cell populations with single cell resolution. Unfortunately,
      classic flow cytometry detects fluorescence from whole cells and does not shed
      light on subcellular dynamics. In this report, we demonstrate the use of
      microfluidics-based total internal reflection fluorescence flow cytometry (TIRF
      FC) for examining initial quantum dot (QD) entry into cells and the associated
      subcellular movement at the single cell level with a rate of ~200 cells s(-1).
      Our cytometric tool allows extraction of quantitative data from a large cell
      population and reveals details about the QD transport in the periphery of the
      cell membrane (~100 nm deep into the cytosol). Our data indicate that the
      fluorescence density at the membrane vicinity decreases after initial QD dosage
      due to the decline in the density of QDs in the evanescent field and the
      transport into the cytosol is very rapid.

PMID- 22358226
TI  - Skin necrosis in patients with arterial catheters flushed with a solution
      containing heparin.

PMID- 22358227
TI  - UVA1 phototherapy: a concise and practical review.
AB  - High intensity long-wavelength ultraviolet A (340-400 nm; UVA1) lamps were
      initially developed as skin research tools; over time they have proven to be
      useful for treating a number of chronic dermatoses. UVA1 units and dosimetry are
      strikingly different from conventional UV phototherapy. The therapeutic effect of
      UVA1 is related to the fact that its long wavelength penetrates the dermis more
      deeply than UVB. UVA1 radiation induces collagenase (matrix metalloproteinase-1)
      expression, T-cell apoptosis, and depletes Langerhans and mast cells in the
      dermis. UVA1 exposure stimulates endothelial cells to undergo neovascularization.
      Ultraviolet A1 exerts significant therapeutic effects in atopic dermatitis and
      morphea; there is also evidence for its use in other skin diseases, including
      cutaneous T-cell lymphoma and mastocytosis.

PMID- 22358228
TI  - Pediatric psoriasis.
AB  - Several variants of psoriasis are seen in children, the most prevalent types
      include plaque, guttate, and psoriatic diaper rash; pustular and erythrodermic
      psoriasis are less frequently observed. Genetic susceptibility and environmental
      triggers are both involved in the development of this autoimmune disease. As well
      as improving symptoms, a treatment plan should strive to identify and eliminate
      precipitating factors. Topical medications are the first choice therapy for
      children with psoriasis. Systemic agents are used to treat more severe cases.
      Patient education and supportive care should be incorporated into the treatment
      plan.

PMID- 22358229
TI  - Two types of oxalate-bridging rare-earth-substituted Keggin-type
      phosphotungstates {[(alpha-PW11O39)RE(H2O)]2(C2O4)}(10-) and {(alpha-x
      PW10O38)RE2(C2O4)(H2O)2}(3-).
AB  - Two types of novel oxalate-bridging rare-earth-substituted Keggin-type
      phosphotungstates {[(alpha-PW(11)O(39)) RE(H(2)O)](2)(C(2)O(4))}(10-) (RE =
      Y(III) for 1, Dy(III) for 2, Ho(III) for 3 and Er(III) for 4) and {(alpha-x
      PW(10)O(38))Tm(2)(C(2)O(4))(H(2)O)(2)}(3-) for 5 have been synthesized by
      reaction of [alpha-PW(11)O(39)](7-) with RE cations and oxalate ligands in
      aqueous solution. They have been further characterized by elemental analyses, X
      ray powder diffraction (XRPD), IR spectra, thermogravimetric (TG) analysis, and
      single-crystal X-ray diffraction. The common features of 1-4 are that they all
      contain the dimeric mono-RE substituted Keggin [RE(alpha-PW(11)O(39))](2)(14-)
      subunits linked by oxalate ligands whereas 5 exhibits a one-dimensional (1D)
      chain architecture built by the unusual divacant [alpha-x-PW(10)O(38)](11-)
      polyoxoanions and oxalate ligands. Notably, 1-5 represent the first oxalate
      bridging dimers constructed by lacunary Keggin phosphotungstate-supported RE
      derivatives, and the unusual divacant [alpha-x-PW(10)O(38)](11-) fragment is
      found for the first time. Furthermore, the room-temperature solid-state
      photoluminescence of 2 has been investigated. Variable-temperature magnetic
      susceptibility measurements indicate that 2 and 4 demonstrate weak ferromagnetic
      couplings within the two adjacent RE cations bridged through oxalate ligands,
      whereas dominant antiferromagnetic interactions are observed in 3 and 5,
      respectively.

PMID- 22358231
TI  - Bioethicists must rethink the concept of death: the idea of brain death is not
      appropriate for cryopreservation.

PMID- 22358232
TI  - Genotype analysis of the human endostatin variant p.D104N in benign and malignant
      adrenocortical tumors.
AB  - OBJECTIVE: Endostatin is a potent endogenous inhibitor of angiogenesis. It is
      derived from the proteolytic cleavage of collagen XVIII, which is encoded by the
      COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism
      p.D104N impairs the activity of endostatin, resulting in a decreased ability to
      inhibit angiogenesis. This polymorphism has been previously analyzed in many
      types of cancer and has been considered a phenotype modulator in some benign and
      malignant tumors. However, these data are controversial, and different results
      have been reported for the same tumor types, such as prostate and breast cancer.
      The purpose of this study was to genotype the p.D104N variant in a cohort of
      pediatric and adult patients with adrenocortical tumors and to determine its
      possible association with the biological behavior of adrenocortical tumors.
      METHODS: DNA samples were obtained from 38 pediatric and 56 adult patients (0.6
      75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral
      blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or
      fresh frozen tissue samples were unavailable. Restriction fragment length
      polymorphism analysis was used to genotype the patients and 150 controls. The
      potential associations of the p.D104N polymorphism with clinical and
      histopathological features and oncologic outcome (age of onset, tumor size,
      malignant tumor behavior, and clinical syndrome) were analyzed. RESULTS: Both the
      patient group and the control group were in Hardy-Weinberg equilibrium. The
      frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD),
      15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3%
      and 2.0%, respectively. We did not observe any association of this variant with
      clinical or histopathological features or oncologic outcome in our cohort of
      pediatric and adult patients with adrenocortical tumors.

PMID- 22358233
TI  - Characterization of human adipose-derived stem cells and expression of
      chondrogenic genes during induction of cartilage differentiation.
AB  - OBJECTIVES: Understanding the changes in chondrogenic gene expression that are
      involved in the differentiation of human adipose-derived stem cells to
      chondrogenic cells is important prior to using this approach for cartilage
      repair. The aims of the study were to characterize human adipose-derived stem
      cells and to examine chondrogenic gene expression after one, two, and three weeks
      of induction. MATERIALS AND METHODS: Human adipose-derived stem cells at passage
      4 were evaluated by flow cytometry to examine the expression of surface markers.
      These adipose-derived stem cells were tested for adipogenic and osteogenic
      differentiation capacity. Ribonucleic acid was extracted from the cells for
      quantitative polymerase chain reaction analysis to determine the expression
      levels of chondrogenic genes after chondrogenic induction. RESULTS: Human adipose
      derived stem cells were strongly positive for the mesenchymal markers CD90, CD73,
      CD44, CD9, and histocompatibility antigen and successfully differentiated into
      adipogenic and osteogenic lineages. The human adipose-derived stem cells
      aggregated and formed a dense matrix after chondrogenic induction. The expression
      of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI,
      COMP, and ELASTIN) was significantly higher after the first week of induction.
      However, a significantly elevated expression of collagen type X was observed
      after three weeks of chondrogenic induction. CONCLUSION: Human adipose-derived
      stem cells retain stem cell characteristics after expansion in culture to passage
      4 and serve as a feasible source of cells for cartilage regeneration.
      Chondrogenesis in human adipose-derived stem cells was most prominent after one
      week of chondrogenic induction.

PMID- 22358234
TI  - Does administering albumin to postoperative gastroschisis patients improve
      outcome?
AB  - OBJECTIVES: Newborns who undergo surgery for gastroschisis correction may present
      with oliguria, anasarca, prolonged postoperative ileus, and infection. New
      postoperative therapeutic procedures were tested with the objective of improving
      postoperative outcome. PATIENTS AND METHODS: One hundred thirty-six newborns
      participated in one of two phases. Newborns in the first phase received infusions
      of large volumes of crystalloid solution and integral enteral formula, and
      newborns in the second phase received crystalloid solutions in smaller volumes,
      with albumin solution infusion when necessary and the late introduction of a semi
      elemental diet. The studied variables were serum sodium and albumin levels, the
      need for albumin solution expansion, the occurrence of anasarca, the length of
      time on parenteral nutrition, the length of time before initiating an enteral
      diet and reaching a full enteral diet, orotracheal intubation time, length of
      hospitalization, and survival rates. RESULTS: Serum sodium levels were higher in
      newborns in the second phase. There was a correlation between low serum sodium
      levels and orotracheal intubation time; additionally, low serum albumin levels
      correlated with the length of time before the initiation of an oral diet and the
      time until a full enteral diet was reached. However, the discharge weights of
      newborns in the second phase were higher than in the first phase. The other
      studied variables, including survival rates (83.4% and 92.0%, respectively), were
      similar for both phases. CONCLUSIONS: The administration of an albumin solution
      to newborns in the early postoperative period following gastroschisis repair
      increased their low serum sodium levels but did not improve the final outcome.
      The introduction of a semi-elemental diet promoted an increase in body weight at
      the time of discharge.

PMID- 22358235
TI  - Establishment of the bacterial fecal community during the first month of life in
      Brazilian newborns.
AB  - OBJECTIVE: The establishment of the intestinal microbiota in newborns is a
      critical period with possible long-term consequences for human health. In this
      research, the development of the fecal microbiota of a group of exclusively
      breastfed neonates living in low socio-economic conditions in the city of Sao
      Paulo, Brazil, during the first month of life, was studied. METHODS: Fecal
      samples were collected from ten neonates on the second, seventh, and 30(th) days
      after birth. One of the neonates underwent antibiotic therapy. Molecular
      techniques were used for analysis; DNA was extracted from the samples, and 16S
      rRNA libraries were sequenced and phylogenetically analyzed after construction. A
      real-time polymerase chain reaction (PCR) was performed on the samples taken from
      the 30(th) day to amplify DNA from Bifidobacterium sp. RESULTS: The primary
      phylogenetic groups identified in the samples were Escherichia and Clostridium.
      Staphylococcus was identified at a low rate. Bifidobacterium sp. was detected in
      all of the samples collected on the 30(th) day. In the child who received
      antibiotics, a reduction in anaerobes and Escherichia, which was associated with
      an overgrowth of Klebsiella, was observed throughout the experimental period.
      CONCLUSION: The observed pattern of Escherichia predominance and reduced
      Staphylococcus colonization is in contrast with the patterns observed in neonates
      living in developed countries.

PMID- 22358236
TI  - Is the measurement of inferior thyroid artery blood flow velocity by color-flow
      Doppler ultrasonography useful for differential diagnosis between gestational
      transient thyrotoxicosis and Graves' disease? A prospective study.
AB  - OBJECTIVE: To determine the role of peak systolic velocity, end-diastolic
      velocity and resistance indices of both the right and left inferior thyroid
      arteries measured by color-flow Doppler ultrasonography for a differential
      diagnosis between gestational transient thyrotoxicosis and Graves' disease during
      pregnancy. METHODS: The right and left inferior thyroid artery-peak systolic
      velocity, end-diastolic velocity and resistance indices of 96 patients with
      thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched
      pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant
      patients with Graves' disease) and 25 age and sex-matched healthy euthyroid
      subjects were assessed with color-flow Doppler ultrasonography. RESULTS: The
      right and left inferior thyroid artery-peak systolic and end-diastolic velocities
      in patients with gestational transient thyrotoxicosis were found to be
      significantly lower than those of pregnant patients with Graves' disease and
      higher than those of healthy euthyroid subjects. However, the right and left
      inferior thyroid artery peak systolic and end-diastolic velocities in pregnant
      patients with Graves' disease were significantly lower than those of non-pregnant
      patients with Graves' disease. The right and left inferior thyroid artery peak
      systolic and end-diastolic velocities were positively correlated with TSH
      receptor antibody levels. We found an overlap between the inferior thyroid artery
      blood flow velocities in a considerable number of patients with gestational
      transient thyrotoxicosis and pregnant patients with Graves' disease. CONCLUSIONS:
      This study suggests that the measurement of inferior thyroid artery-blood flow
      velocities with color-flow Doppler ultrasonography does not have sufficient
      sensitivity and specificity to be recommended as an initial diagnostic test for a
      differential diagnosis between gestational transient thyrotoxicosis and Graves'
      disease during pregnancy.

PMID- 22358237
TI  - Liver enzymes in patients with chronic kidney disease undergoing peritoneal
      dialysis and hemodialysis.
AB  - OBJECTIVE: The present study was designed to analyze the serum levels of
      aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the
      hematocrit in patients with chronic kidney disease who were undergoing peritoneal
      dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal
      dialysis and 40 on hemodialysis were assessed, and the patients were matched
      according to the length of time that they had been on dialysis. Blood samples
      were collected (both before and after the session for those on hemodialysis) to
      measure the enzymes and the hematocrit. RESULTS: In the samples from the patients
      who were undergoing peritoneal dialysis, the aspartate and alanine
      aminotransferase levels were slightly higher compared with the samples collected
      from the patients before the hemodialysis session and slightly lower compared
      with the samples collected after the hemodialysis session. The levels of gamma
      glutamyl transferase in the hemodialysis patients were slightly higher than the
      levels in the patients who were undergoing peritoneal dialysis. In addition, the
      levels of aminotransferases and gamma-glutamyl transferase that were collected
      before the hemodialysis session were significantly lower than the values
      collected after the session. The hematocrit levels were significantly lower in
      the patients who were on peritoneal dialysis compared with the patients on
      hemodialysis (both before and after the hemodialysis session), and the levels
      were also significantly lower before hemodialysis compared with after
      hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were
      undergoing peritoneal dialysis were slightly higher compared with the samples
      collected before the hemodialysis session, whereas the aminotransferase levels
      were slightly lower compared with the samples collected after the session. The
      hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the
      samples collected after the hemodialysis session were significantly higher than
      the samples collected before the session. Taken together, the present data
      suggest that hemodilution could alter the serum levels of liver enzymes.

PMID- 22358238
TI  - Gamma-tocotrienol modulation of senescence-associated gene expression prevents
      cellular aging in human diploid fibroblasts.
AB  - OBJECTIVE: Human diploid fibroblasts undergo a limited number of cellular
      divisions in culture and progressively reach a state of irreversible growth
      arrest, a process termed cellular aging. The beneficial effects of vitamin E in
      aging have been established, but studies to determine the mechanisms of these
      effects are ongoing. This study determined the molecular mechanism of gamma
      tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human
      diploid fibroblasts using the expression of senescence-associated genes. METHODS:
      Primary cultures of young, pre-senescent, and senescent fibroblast cells were
      incubated with gamma-tocotrienol for 24 h. The expression levels of ELN, COL1A1,
      MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time
      polymerase chain reaction. Cell cycle profiles were determined using a
      FACSCalibur Flow Cytometer. RESULTS: The cell cycle was arrested in the G(0)/G(1)
      phase, and the percentage of cells in S phase decreased with senescence. CCND1,
      RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar
      upregulation was not observed in young cells. Incubation with gamma-tocotrienol
      decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell
      populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M
      phase. gamma-Tocotrienol treatment also upregulated ELN and COL1A1 and
      downregulated MMP1 and IL6 expression in young and senescent fibroblasts.
      CONCLUSION: gamma-Tocotrienol prevented cellular aging in human diploid
      fibroblasts, which was indicated by the modulation of the cell cycle profile and
      senescence-associated gene expression.

PMID- 22358240
TI  - Classification of the severity of diabetic neuropathy: a new approach taking
      uncertainties into account using fuzzy logic.
AB  - OBJECTIVE: This study proposes a new approach that considers uncertainty in
      predicting and quantifying the presence and severity of diabetic peripheral
      neuropathy. METHODS: A rule-based fuzzy expert system was designed by four
      experts in diabetic neuropathy. The model variables were used to classify
      neuropathy in diabetic patients, defining it as mild, moderate, or severe. System
      performance was evaluated by means of the Kappa agreement measure, comparing the
      results of the model with those generated by the experts in an assessment of 50
      patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50
      other cases; the results of those clinical assessments were considered to be the
      gold standard. RESULTS: According to the Kappa analysis, the model was in
      moderate agreement with expert opinions. The ROC analysis (evaluation of
      accuracy) determined an area under the curve equal to 0.91, demonstrating very
      good consistency in classifying patients with diabetic neuropathy. CONCLUSION:
      The model efficiently classified diabetic patients with different degrees of
      neuropathy severity. In addition, the model provides a way to quantify diabetic
      neuropathy severity and allows a more accurate patient condition assessment.

PMID- 22358239
TI  - Visual acuity and retinal function in patients with Bardet-Biedl syndrome.
AB  - OBJECTIVE: Bardet-Biedl syndrome is a genetic, multisystem disorder that causes
      severe visual impairment. This condition is characterized by retinal dystrophy,
      obesity, digit anomalies, renal disease, and hypogonadism. The purpose of this
      study was to analyze visual acuity and full-field electroretinogram findings in
      patients with the Bardet-Biedl syndrome phenotype. METHODS: The visual acuity of
      a group of 23 patients (15 males) with ages ranging from 6-36 years (mean = 15.8
      +/- 6.4; median = 14.7) was assessed. Retinal function was evaluated by full
      field electroretinography, and dark-adapted thresholds were assessed. RESULTS:
      Visual acuity in the better-seeing eye was 20/40 or better in 5 patients (21.7%),
      20/50-20/150 in 13 (56.5%) patients, 20/200-20/400 in 2 (8.7%) patients and worse
      than 20/400 in one (4.3%) patient. The mean acuity in the better-seeing eye was
      0.7 +/- 0.6 logMAR (20/100, Snellen equivalent). Scotopic rod and maximal
      responses were nondetectable in 21 (91.3%) patients, and cone responses were non
      detectable in 15 (65.2%) patients. Elevated dark-adapted visual thresholds were
      observed in all 19 patients who were able to be assessed, with 10 (52.6%)
      patients having thresholds greater than 30 dB. CONCLUSIONS: In a relatively young
      cohort of patients with Bardet-Biedl syndrome, only 21% had 20/40 or better
      vision. ERG scotopic responses were absent in the majority of cases, with cone
      responses being observed in less than half of cases. These findings showed the
      early deleterious effects in retinal function and visual acuity caused by this
      condition.

PMID- 22358241
TI  - Clinical and serological manifestations associated with interferon-alpha levels
      in childhood-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset
      systemic lupus erythematosus patients, their first-degree relatives and healthy
      controls and to evaluate the associations between serum interferon alpha and
      disease activity, laboratory findings and treatment features. METHODS: We
      screened consecutive childhood-onset systemic lupus erythematosus patients in a
      longitudinal cohort at the pediatric rheumatology unit of the State University of
      Campinas between 2009 and 2010. All patients demonstrated disease onset before
      the age of 16. Disease status was assessed according to the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index (SDI).
      Interferon alpha levels were measured using an enzyme-linked immunoabsorbent
      assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus
      patients (mean age 17.33 +/- 4.50), 64 first-degree relatives (mean age 39.95 +/-
      5.66), and 57 healthy (mean age 19.30 +/- 4.97) controls. Serum interferon alpha
      levels were significantly increased in childhood-onset systemic lupus
      erythematosus patients compared to their first-degree relatives and healthy
      controls. Interferon alpha levels were significantly increased in patients with
      positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new
      malar rash and patients who were not receiving medication. Interferon alpha
      levels correlated with C3 levels and systemic lupus erythematosus Disease
      Activity Index scores. In addition, we observed an inverse correlation between
      patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a
      role in the pathogenesis of childhood-onset systemic lupus erythematosus,
      especially in cutaneous manifestations and dsDNA antibody formation. The
      observation that interferon alpha levels are increased in patients who are not
      taking medication should be investigated in longitudinal studies to determine
      whether elevated interferon alpha levels may predict systemic lupus erythematosus
      flares.

PMID- 22358242
TI  - Comparison of two peptide radiotracers for prostate carcinoma targeting.
AB  - OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate
      cancer, although successful studies using bombesin analog radiopeptides have been
      performed. Recently, a novel peptide obtained using a phage display library
      demonstrated an affinity for prostate tumor cells. The aim of this study was to
      compare the use of a bombesin analog to that of a phage display library peptide
      (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma.
      The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer,
      namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium
      tartrate buffer. Radiochemical evaluation was performed using ITLC and was
      confirmed by high-performance liquid chromatography. The coefficient partition
      was determined, and in vitro studies were performed using human prostate tumor
      cells. Biodistribution was evaluated in healthy animals at various time points
      and also in mice bearing tumors. RESULTS: The radiochemical purity of both
      radiotracers was greater than 95%. The DUP-1 tracer was more hydrophilic (log P =
      -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation
      confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1.
      The bombesin concentration in the pancreas was greater than that of DUP-1 due to
      specific gastrin-releasing peptide receptors. Bombesin internalization occurred
      for 78.32% of the total binding in tumor cells. The DUP-1 tracer showed very low
      binding to tumor cells during the in vitro evaluation, although tumor uptake for
      both tracers was similar. The tumors were primarily blocked by DUP1 and the
      bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies
      with the radiolabeled DUP-1 peptide are recommended. With further structural
      changes, this molecule could become an efficient alternative tracer for prostate
      tumor diagnosis.

PMID- 22358243
TI  - The protective effect of cilostazol on isolated rabbit femoral arteries under
      conditions of ischemia and reperfusion: the role of the nitric oxide pathway.
AB  - OBJECTIVES: The clinical significance of ischemia/reperfusion of the lower
      extremities demands further investigation to enable the development of more
      effective therapeutic alternatives. This study investigated the changes in the
      vascular reactivity of the rabbit femoral artery and nitric oxide metabolites
      under partial ischemia/ reperfusion conditions following cilostazol
      administration. METHODS: Ischemia was induced using infrarenal aortic clamping.
      The animals were randomly divided into seven groups: Control 90 minutes,
      Ischemia/Reperfusion 90/60 minutes, Control 120 minutes, Ischemia/Reperfusion
      120/90 minutes, Cilostazol, Cilostazol before Ischemia/Reperfusion 120/90
      minutes, and Ischemia 120 minutes/Cilostazol/ Reperfusion 90 minutes. Dose
      response curves for sodium nitroprusside, acetylcholine, and the calcium
      ionophore A23187 were obtained in isolated femoral arteries. The levels of
      nitrites and nitrates in the plasma and skeletal muscle were determined using
      chemiluminescence. RESULTS: Acetylcholine-and A23187-induced relaxation was
      reduced in the Ischemia/Reperfusion 120/90 group, and treatment with cilostazol
      partially prevented this ischemia/reperfusion-induced endothelium impairment.
      Only cilostazol treatment increased plasma levels of nitrites and nitrates. An
      elevation in the levels of nitrites and nitrates was observed in muscle tissues
      in the Ischemia/Reperfusion 120/90, Cilostazol/Ischemia/Reperfusion, and
      Ischemia/ Cilostazol/Reperfusion groups. CONCLUSION: Hind limb
      ischemia/reperfusion yielded an impaired endothelium-dependent relaxation of the
      femoral artery. Furthermore, cilostazol administration prior to ischemia exerted
      a protective effect on endothelium-dependent vascular reactivity under
      ischemia/reperfusion conditions.

PMID- 22358244
TI  - The detection of cysto-biliary communications during surgery for liver hydatid
      cysts: let's speak the unspoken.

PMID- 22358245
TI  - Prevalence of erectile dysfunction in chronic renal disease patients on
      conservative treatment.

PMID- 22358246
TI  - Interobserver concordance in the BI-RADS classification of breast ultrasound
      exams.

PMID- 22358247
TI  - Paroxetine-induced severe sleep bruxism successfully treated with buspirone.

PMID- 22358248
TI  - Acupuncture and exercise capacity: a case report.

PMID- 22358249
TI  - A combined minimally invasive approach for the treatment of aortoesophageal
      fistula caused by the ingestion of a chicken bone: case report and literature
      review.

PMID- 22358250
TI  - Laparoscopic repair of an incarcerated bochdalek hernia in an elderly man.

PMID- 22358251
TI  - Spectrum of excess partial molar absorptivity. Part II: a near infrared
      spectroscopic study of aqueous Na-halides.
AB  - Our earlier thermodynamic studies suggested that F(-) and Cl(-) form hydration
      shells with the hydration number 14 +/- 2 and 2.3 +/- 0.6, respectively, and
      leave the bulk H(2)O away from hydration shells unperturbed. Br(-) and I(-), on
      the other hand, form hydrogen bonds directly with the momentarily existing
      hydrogen bond network of H(2)O, and retard the degree of entropy-volume cross
      fluctuation inherent in liquid H(2)O. The effect of the latter is stronger for I(
      ) than Br(-). Here we seek additional information about this qualitative
      difference between Cl(-) and (Br(-) and I(-)) pair by near infrared (NIR)
      spectroscopy. We analyze the nu(2) + nu(3) band of H(2)O in the range 4600-5500
      cm(-1) of aqueous solutions of NaCl, NaBr and NaI, by a new approach. From
      observed absorbance, we calculate excess molar absorptivity, epsilon(E), excess
      over the additive contributions of solute and solvent. epsilon(E) thus contains
      information about the effect of inter-molecular interactions in the nu(2) + nu(3)
      spectrum. The spectrum of epsilon(E) shows three bands; two negative ones at 5263
      and 4873 cm(-1), and the positive band at 5123 cm(-1). We then define and
      calculate the excess partial molar absorptivity of each salt, epsilon(E)(salt).
      From the behaviour of epsilon(E)(salt) we suggest that the negative band at 5263
      cm(-1) represents free H(2)O without much hydrogen bonding under the influence of
      local electric field of ions. Furthermore, from a sudden change in the x(salt)
      (mole fraction of salt) dependence of epsilon(E)(salt), we suggest that there is
      an ion-pairing in x(salt) > 0.032, 0.036, and 0.04 for NaCl, NaBr and NaI
      respectively. The positive band of epsilon(E) at 5123 cm(-1) is attributed to a
      modestly organized hydrogen bond network of H(2)O (or liquid-likeness), and the
      x(salt) dependence of epsilon indicated a qualitative difference in the effect of
      Cl(-) from those of Br(-) and I(-). Namely, the values of epsilon(E)(salt) stay
      constant for Cl(-) but those for Br(-) and I(-) decrease smoothly on increasing
      the salt mole fraction. The mole fraction dependence of epsilon(E)(salt) at the
      4873 cm(-1) band, due to ice-likeness in H(2)O, shows a subtle difference between
      Cl(-) and (Br(-), I(-)) pair.

PMID- 22358252
TI  - Friction Modeling in Concentric Tube Robots.
AB  - Concentric tube robots are a novel class of continuum robots that are constructed
      by combining pre-curved elastic tubes such that the overall shape of the robot is
      a function of the relative rotations and translations of the constituent tubes.
      Frictionless kinematic and quasistatic force models for this class of robots have
      been developed that incorporate bending and twisting of the tubes. Experimental
      evaluation of these models has revealed, however, a directional dependence of
      tube rotation on robot shape that is not predicted by these models. To explain
      this behavior, this paper models the contributions of friction arising from two
      sources: the distributed forces of contact between the tubes along their length
      and the concentrated bending moments generated at discontinuities in curvature
      and at the boundaries. It is shown that while friction due to distributed forces
      is insufficient to explain the experimentally observed tube twisting, a simple
      model of frictional torque arising from concentrated moments provides a good
      match with the experimental data.

PMID- 22358254
TI  - A pediatric case of an unusual type of annular pancreas presenting with
      duodenopancreatic reflux.
AB  - Pancreatitis, a late complication of an annular pancreas (AP), results from
      coexisting pancreaticobiliary malformations including pancreas divisum (PD), and
      pancreaticobiliary maljunction (PBM). The authors report the case of a 3-year-old
      boy with an unusual type of AP in which the dorsal anlage encircled the duodenum.
      The patient developed duodenal obstruction as well as duodenopancreatic reflux
      with resulting hyperamylasemia and hyperlipasemia. This type of AP associated
      with duodenopancreatic reflux in AP has not been reported previously. The patient
      was successfully treated by duodenoduodenostomy, which, by correcting the
      duodenopancreatic reflux, prevented the later development of pancreatitis.

PMID- 22358253
TI  - Re-operation for Hirschsprung's disease: experience in 24 patients from China.
AB  - PURPOSE: The aim of this study is to review the authors' 12-year experience with
      re-operative surgery for Hirschsprung's disease (HD) including indications of re
      operation and surgical technique. METHODS: We retrospectively reviewed the data
      of 24 patients who underwent re-operation from 1998 to 2010. The type of initial
      procedure, clinical presentations, indications and details of redo surgery, and
      the functional results were analyzed. RESULTS: The primary operations performed
      on these patients included Duhamel (nine cases), Soave (12 cases), Swenson (one
      case) and Rehbein (two cases). The indications for re-operation were recurrent
      constipation due to severe anastomotic stricture (five cases), residual
      aganglionic segments (five cases) and gate syndrome after Duhamel procedure (five
      cases); fistula formation including rectocutaneous fistula (six cases),
      rectovaginal fistula (one case), complex fistula (two cases). The redo procedure
      ranged from posterior sagittal approach combined with laparotomy (seven cases),
      Soave procedure (seven cases, six conventional Soave + one transanal Soave),
      Duhamel procedure (one case), Rehbein procedure (three cases), re-using the
      stapling device (five cases), repairing the rectovaginal fistula via laparotomy
      (one case). We have followed up the patients for 7 months to 6 years (mean 2.5
      years). After re-operation, in 22 patients older than 3 years, 19 (86.4%) have
      normal or near normal bowel habits with a stool frequency of 1-5 times per day,
      two have voluntary bowel movements but occasional soiling (once or twice per
      week) and without significant incontinence, one presented rectosacral fistula due
      to careless dilatation. There were no deaths. CONCLUSION: Re-operation can work
      out the anatomical or pathological problems resulted from failed initial
      procedure and improve the patient's quality of life. Posterior sagittal approach,
      Soave and Duhamel are all safe and effective, but we still need to try our best
      to diminish the necessity of re-operation.

PMID- 22358255
TI  - Ultrafast IR spectroscopy of polymeric cytosine nucleic acids reveal the long
      lived species is due to a localised state.
AB  - The decay pathways of UV-excited cytosine polymers are investigated using
      picosecond time-resolved infrared spectroscopy. Similar yields of a non-emissive
      (1)npi* state are found in the single-stranded dC(30) polymer as in the dCMP
      monomer, but with a longer lifetime in the polymer (80 ps vs. 39 ps). A longer
      lifetime is also found in the d(CpC) dinucleotide. No evidence of excimer states
      is observed, suggesting that localised (1)npi* excited states are the most
      significant intermediates present on the picosecond timescale.

PMID- 22358256
TI  - The oxidation of natural flavonoid quercetin.
AB  - This study explains the controversies in the literature concerning the number of
      electrons involved in the oxidation of quercetin. This stems from inappropriate
      handling samples, which require strict anaerobic conditions. The redox potential
      of quercetin strongly depends on the pH and on the presence of dissociation forms
      in solution.

PMID- 22358257
TI  - Solid-phase route to Fmoc-protected cationic amino acid building blocks.
AB  - Diamino acids are commonly found in bioactive compounds, yet only few are
      commercially available as building blocks for solid-phase peptide synthesis. In
      the present work a convenient, inexpensive route to multiple-charged amino acid
      building blocks with varying degree of hydrophobicity was developed. A versatile
      solid-phase protocol leading to selectively protected amino alcohol intermediates
      was followed by oxidation to yield the desired di- or polycationic amino acid
      building blocks in gram-scale amounts. The synthetic sequence comprises loading
      of (S)-1-(p-nosyl)aziridine-2-methanol onto a freshly prepared trityl bromide
      resin, followed by ring opening with an appropriate primary amine, on-resin
      N(beta)-Boc protection of the resulting secondary amine, exchange of the N(alpha)
      protecting group, cleavage from the resin, and finally oxidation in solution to
      yield the target gamma-aza substituted building blocks having an Fmoc/Boc
      protection scheme. This strategy facilitates incorporation of multiple positive
      charges into the building blocks provided that the corresponding partially
      protected di- or polyamines are available. An array of compounds covering a wide
      variety of gamma-aza substituted analogs of simple neutral amino acids as well as
      analogs displaying high bulkiness or polycationic side chains was prepared. Two
      building blocks were incorporated into peptide sequences using microwave-assisted
      solid-phase peptide synthesis confirming their general utility.

PMID- 22358258
TI  - Optimizing human in vivo dosing and delivery of beta-alanine supplements for
      muscle carnosine synthesis.
AB  - Interest into the effects of carnosine on cellular metabolism is rapidly
      expanding. The first study to demonstrate in humans that chronic beta-alanine
      (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly
      augmented muscle carnosine concentrations (>50%) was only recently published. BA
      supplementation is potentially poised for application beyond the niche exercise
      and performance-enhancement field and into other more clinical populations. When
      examining all BA supplementation studies that directly measure muscle carnosine
      (n=8), there is a significant linear correlation between total grams of BA
      consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative
      and absolute increases in muscle carnosine. Supporting this, a recent dose
      response study demonstrated a large linear dependency (R2=0.921) based on the
      total grams of BA consumed over 8 weeks. The pre-supplementation baseline
      carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear
      to impact on subsequent carnosine synthesis from BA consumption. Once muscle
      carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow
      release BA tablet supplement has been developed showing a smaller peak plasma BA
      concentration and delayed time to peak, with no difference in the area under the
      curve compared to pure BA in solution. Further, this slow-release profile
      resulted in a reduced urinary BA loss and improved retention, while at the same
      time, eliciting minimal paraesthesia symptoms. However, our complete
      understanding of optimizing in vivo delivery and dosing of BA is still in its
      infancy. Thus, this review will clarify our current knowledge of BA
      supplementation to augment muscle carnosine as well as highlight future research
      questions on the regulatory points of control for muscle carnosine synthesis.

PMID- 22358259
TI  - Stepwise adsorption in a mesoporous metal-organic framework: experimental and
      computational analysis.
AB  - Stepwise adsorption in a metal-organic framework with both micro- and meso-pores
      is caused by adsorbates first filling the micropores, then adsorbing along the
      mesopore walls, and finally filling the mesopores.

PMID- 22358260
TI  - Multivariable passive RFID vapor sensors: roll-to-roll fabrication on a flexible
      substrate.
AB  - We demonstrate roll-to-roll (R2R) fabrication of highly selective, battery-free
      radio frequency identification (RFID) sensors on a flexible polyethylene
      terephthalate (PET) polymeric substrate. Selectivity of our developed RFID
      sensors is provided by measurements of their resonance impedance spectra,
      followed by the multivariate analysis of spectral features, and correlation of
      these spectral features to the concentrations of vapors of interest. The
      multivariate analysis of spectral features also provides the ability for the
      rejection of ambient interferences. As a demonstration of our R2R fabrication
      process, we employed polyetherurethane (PEUT) as a "classic" sensing material,
      extruded this sensing material as 25, 75, and 125-MUm thick films, and thermally
      laminated the films onto RFID inlays, rapidly producing approximately 5000 vapor
      sensors. We further tested these RFID vapor sensors for their response
      selectivity toward several model vapors such as toluene, acetone, and ethanol as
      well as water vapor as an abundant interferent. Our RFID sensing concept features
      16-bit resolution provided by the sensor reader, granting a highly desired
      independence from costly proprietary RFID memory chips with a low-resolution
      analog input. Future steps are being planned for field-testing of these sensors
      in numerous conditions.

PMID- 22358261
TI  - Optical and electrochemical properties of hydrogen-bonded phenol
      pyrrolidino[60]fullerenes.
AB  - We report the photophysical and electrochemical properties of phenol
      pyrrolidino[60]fullerenes 1 and 2, in which the phenol hydroxyl group is ortho
      and para to the pyrrolidino group, respectively, as well as those of a phenyl
      pyrrolidino[60]fullerene model compound, 3. For the ortho analog 1, the presence
      of an intramolecular hydrogen bond is supported by (1)H NMR and FTIR
      characterization. The redox potential of the phenoxyl radical-phenol couple in
      this architecture is 240 mV lower than that observed in the associated para
      compound 2. Further, the C(60) excited-state lifetime of the hydrogen-bonded
      compound 1 in benzonitrile is 260 ps, while the corresponding lifetime for 2 is
      identical to that of the model compound 3 at 1.34 ns. Addition of excess organic
      acid to a benzonitrile solution of 1 gives rise to a new species, 4, with an
      excited-state lifetime of 1.40 ns. In nonpolar aprotic solvents such as toluene,
      all three compounds have a C(60) excited-state lifetime of ~1 ns. These results
      suggest that the presence of an intramolecular H-bond in 1 poises the potential
      of phenoxyl radical-phenol redox couple at a value that it is thermodynamically
      capable of reducing the photoexcited fullerene. This is not the case for the para
      analog 2 nor is it the case for the protonated species 4. This work illustrates
      that in addition to being used as light activated electron acceptors, pyrrolidino
      fullerenes are also capable of acting as built-in proton-accepting units that
      influence the potential of an attached donor when organized in an appropriate
      molecular design.

PMID- 22358262
TI  - Improvement of motor evoked potentials monitoring is required during thoracic or
      thoracoabdominal aortic aneurysm surgery under hypothermic cardiopulmonary
      bypass.

PMID- 22358264
TI  - Intensive chemotherapy to improve outcome in patients with acute lymphoblastic
      leukemia over the age of 40: a phase II study for efficacy and feasibility by
      HOVON.

PMID- 22358265
TI  - Interfacial organic synthesis in a simple droplet-based microfluidic system.
AB  - A spherical liquid-liquid interface can be obtained by dispersing one liquid
      phase into another to form droplets, which will facilitate the two-phase
      reactions between the immiscible participating fluids. The phase transfer
      catalysts assembled at the droplet "wall" catalyze the reactions between the
      aqueous and organic phases. The study illustrates an interfacial synthetic
      approach which is ideal for the biphasic reaction by taking advantage of the
      droplet-based microdevice. The improved reaction efficiency can be attributed to
      the high surface-to-volume ratio and internal flow circulation in the droplets.

PMID- 22358266
TI  - On-pump coronary artery bypass graft surgery: biochemical, hormonal and cellular
      features.
AB  - OBJECTIVE: The authors sought to assess biochemical, hormonal and cellular
      repercussions from use of cardiopulmonary bypass (CPB) in coronary artery bypass
      graft (CABG) surgery. METHODS: Eighteen patients underwent on-pump CABG surgery.
      Mean time of CPB was 80.3 minutes. Hormonal, biochemical and cellular
      measurements were taken in some time points - preoperatively, immediately after
      coming off CPB, 24 and 48 hours postoperatively. Friedman and Wilcoxon tests were
      applied based on significance level of 5%. RESULTS: There was activation and
      significant elevation of total leukocytes and neutrophils count over CPB,
      remaining this way up to 48 hours postoperatively. Total platelets count, in
      turn, was marked by relevant reduction immediately after coming off CPB as well
      as in two postoperative time points. Serum levels of total proteins and albumin,
      immediately after coming off CPB and also in two postoperative time points, were
      significantly decreased comparing with preoperative status. There was remarkable
      reduction of total T3, free T3 and total T4 particularly up to first 24 hours
      postoperatively. CONCLUSION: In on-pump CABG surgery, inflammatory effects
      encompass activation of total leukocytes, neutrophils and platelets, reduction of
      serum level of total proteins and albumin and decreased thyroid hormones levels,
      especially within first postoperative 24 hours.

PMID- 22358267
TI  - Computed tomography in late evaluation of surgical treatment of pulmonary veins
      total anomalous connection.
AB  - OBJECTIVE: To evaluate if the findings of multislice computed tomography (MSCT)
      are associated with clinical and laboratory tests routinely used in the late
      follow-up of children undergoing surgical treatment of total anomalous pulmonary
      venous connection (TAPVC). METHODS: From January 2002 to December 2007, 12
      patients operated due to CATVP were evaluated with history, physical examination,
      chest X-ray, electrocardiogram, echocardiography and MSCT. Specific changes
      observed in each one of these tests were identified and compared with MSCT
      qualitative findings. RESULTS: Eleven patients were in functional class I (NYHA),
      three had nonspecific murmurs, and three were below the 15th percentile of weight
      and height. Two had pulmonary field abnormalities and three had a slight increase
      of the cardiac area in the X-ray examination. In the electrocardiogram, one
      patient had right ventricular overload and one had junctional rhythm. All
      echocardiograms were within the normal range, except for one patient with
      stenosis between the superior vena cava and right atrium. MSCT was completely
      normal in four patients, three had compression of the pulmonary veins and four
      had significant caliber reduction, which correlated with the other findings.
      Thus, MSCT showed a sensitivity of 87.5%, specificity of 0.75%, positive
      predictive value of 87.5%, negative predictive value of 75% and accuracy of 83.3%
      to demonstrate anatomic changes compared to changes in the physical examination
      or other additional tests. CONCLUSION: MSTC may provide valuable information and
      complement the diagnosis of possible anatomical and functional changes in the
      late follow-up of patients undergoing surgical repair of TAPVC.

PMID- 22358268
TI  - The renewed concept of the Batista operation for ischemic cardiomyopathy: maximum
      ventricular reduction.
AB  - OBJECTIVES: The reconstruction of the left ventricle (LV) is effective in the
      treatment of ischemic cardiomyopathy with large akinetic or dyskinetic areas.
      However, late survival outcomes are related to the remnant left ventricular
      cavity size, thus eliminating intracavitary patch placement provides additional
      LV reduction. The aim of this study was to analyze the results with left
      ventricular reconstruction surgery using the concept of maximum ventricular
      reduction, with systematic patch abolition. METHODS: Seventy-six consecutive
      patients with ischemic heart disease (age 30-78 years, mean 57.6 +/- 10.1),
      evolving in functional class III and IV underwent surgical ventricular
      reconstruction with no use of intracavitary patches or Teflon strips for closing
      the left ventriculotomy. RESULTS: The left ventricular end-systolic diameter
      decreased from 52.3 +/- 5.4 in the preoperative period to 45.2 +/- 6.9 mm in the
      postoperative period. LV ejection fraction increased from 34.2% +/- 10.4% to
      45.5% +/- 9.4%. Associated CABG was performed in 75/76 patients with a mean of
      2.4 grafts per patient. The 30-day mortality was 3/76 (3.9%). At an average
      follow up of 39 months, the majority of the patients (91.4%) remain in functional
      class I and II. CONCLUSION: The concept of maximizing LV reduction with
      systematic patchless reconstruction is feasible, safe and effective, the early
      and late outcomes comparing favorably to previous series reported in the medical
      literature. Additionally, the concept meets the contemporary pathophysiologic
      basis of heart failure.

PMID- 22358269
TI  - Predictors of transfusion of packed red blood cells in coronary artery bypass
      grafting surgery.
AB  - OBJECTIVES: Finding predictors of blood transfusion may facilitate the most
      efficient approach for the use of blood bank services in coronary artery bypass
      grafting procedures. The aim of this retrospective study is to identify
      preoperative and intraoperative patient characteristics predicting the need for
      blood transfusion during or after CABG in our local cardiac surgical service.
      METHODS: 435 patients undergoing isolated first-time CABG were reviewed for their
      preoperative and intraoperative variables and analyzed postoperative data.
      Patients were 255 males and 180 females, with mean age 62.01 +/- 10.13 years.
      Regression logistic analysis was used for identifying the strongest perioperative
      predictors of blood transfusion. RESULTS: Blood transfusion was used in 263
      patients (60.5%). The mean number of transfused blood products units per patient
      was 2.27 +/- 3.07 (0-23) units. The total number of transfused units of blood
      products was 983. Univariate analysis identified age >65 years, weight <70 Kg,
      body mass index <25 Kg/m2, hemoglobin <13mg/dL, hematocrit < 40% and ejection
      fraction <50%, use of cardiopulmonary bypass (CPB), not using an internal
      thoracic artery as a bypass, and multiple bypasses as significant predictors. The
      strongest predictors using multivariate analysis were hematocrit < 40% (OR 2.58;
      CI 1.62-4.15; P<0.001), CPB use (OR 2.00; CI 1.27-3.17; P=0.003) and multiple
      bypasses (OR 2.31; CI 1.31-4.08; P=0.036). CONCLUSIONS: The identification of
      these risk factors leads to better identification of patients with a greater
      probability of using blood, allocation blood bank resources and cost
      effectiveness use of blood products.

PMID- 22358270
TI  - Late outcomes of mitral repair in rheumatic patients.
AB  - INTRODUCTION AND AIMS: The long-term results after surgical repair of rheumatic
      mitral valve remain controversial in literature. Our aim was to determine the
      predictive factors which impact the long-term results after isolated rheumatic
      mitral valve repair and to evaluate the effect of those factors on reoperation
      and late mortality. METHODS: One hundred and four patients with rheumatic valve
      disease who had undergone mitral valve repair with or without tricuspid valve
      annuloplasty were included. All patients with associated procedures were
      excluded. The predictive variables for reoperation were assessed with Cox
      regression and Kaplan Meier survival curves. RESULTS: The mean follow-up time was
      63 +/- 39 months (CI 95% 36 to 74 months). The functional class III and IV was
      observed in 65.4% of all patients. The posterior ring annuloplasty was performed
      in 33 cases, comissutoromy in 21 cases, and comissurotomy with posterior ring
      annuloplasty in 50 patients. There was no operative mortality. The late mortality
      was 2.8% (three patients). The late reoperation was associated with residual
      mitral valve regurgitation after surgery (P<0.001), pulmonary hypertension at the
      pre-operative time (P<0.001), age (P<0.04) and functional class at the post
      operative time (P<0.001). We observed freedom from reoperation rates at 5 and 10
      years of 91.2 +/- 3.4% and 71.1 +/- 9.2%, respectively. CONCLUSION: Repair of
      mitral valve in rheumatic valve disease is feasible with good long-term outcomes.
      Preoperative pulmonary hypertension, residual mitral valve regurgitation after
      surgery, age and functional class are predictors of late reoperation.

PMID- 22358271
TI  - Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation
      in rheumatic mitral disease.
AB  - OBJECTIVE: To analyze the effectiveness of surgical treatment of atrial
      fibrillation (AF) using bipolar radiofrequency ablation during mitral valve
      procedures of rheumatic etiology in heart surgery. METHODS: We retrospectively
      reviewed medical registries of 53 patients submitted to atrial ablation with
      bipolar radiofrequency energy during mitral valve surgery. Thirty four (64%)
      patients were women and the age varied from 27 to 72 years old (average: 49.3 +/-
      10.7 years). Aortic and/or tricuspid procedures were also present in 36 (68%)
      patients. Average time of reported atrial fibrillation was 41 months (from 3 to
      192 months). Type of AF was classified as: paroxysmal in 8 patients, persistent
      in 3, permanent in 42. Left atrium had an average size of 52.9 +/- 8.5 mm. The
      surgeries in these series were: 47 mitral valve replacements and 6 mitral valve
      repairs. Electrocardiografic follow up was 83% complete in 14 months. Data from
      24h Holter were explored. RESULTS: Seven (13%) perioperative deaths were observed
      and survival after 14 months was 87%. Observed heart rhythm after 1 year of
      surgery was sinus rhythm in 25 (66%) patients, AF in 7 (18%), flutter in 7 (13%),
      junctional in 1 (3%). CONCLUSION: Bipolar radiofrequency ablation in patients
      submitted to mitral valve surgery of rheumatic etiology is effective in
      converting to sinus rhythm in 68% of patients after 14 months.

PMID- 22358272
TI  - Elevated plasma D-dimer and hypersensitive C-reactive protein levels may indicate
      aortic disorders.
AB  - OBJECTIVE: D-dimer and C-reactive protein are of diagnostic and predictive values
      in patients have thrombotic tendency, such as vascular thrombosis, coronary
      artery disease and aortic dissection. However, the comparative study in these
      biomarkers between the patients with acute aortic dissection and coronary artery
      disease has not been sufficiently elucidated. METHODS: Consecutive surgical
      patients for acute type A aortic dissection (20 patients), aortic aneurysm (nine
      patients) or coronary artery disease (20 patients) were selected into this study.
      Plasma from preoperative blood samples and supernatant of aortic homogenate of
      the surgical specimens were detected for D-dimer and hypersensitive C-reactive
      protein (hs-CRP). RESULTS: Plasma D-dimer and hs-CRP values in type A aortic
      dissection or aortic aneurysm were much higher than in coronary artery disease
      patients or the healthy control (for D-dimer, aortic dissection: coronary artery
      disease, 0.4344 +/- 0.2958 ug/ml vs. 0.0512 +/- 0.0845 ug/ml, P < 0.0001; aortic
      dissection: healthy control, 0.4344 +/- 0.2958 ug/ml vs. 0.1250 +/- 0.1295 ug/ml,
      P = 0.0005; aortic aneurysm: coronary artery disease, 0.4200 +/- 0.4039 ug/ml vs.
      0.0512 +/- 0.0845 ug/ml, P = 0.0013; and aortic aneurysm: healthy control, 0.4200
      +/- 0.4039 ug/ml vs. 0.1250 +/- 0.1295 ug/ml, P = 0.0068; and for hs-CRP, aortic
      dissection: coronary artery disease, 4.400+/- 3.004 mg/L vs. 1.232+/-0.601 mg/L,
      P < 0.0001; aortic dissection:healthy control, 4.400 +/- 3.004 mg/L vs. 0.790 +/-
      0.423 mg/L, P < 0.0001; aortic aneurysm: coronary artery disease, 2.314 +/- 1.399
      mg/L vs. 1.232 +/- 0.601 mg/L, P = 0.0084; aortic aneurysm: healthy control,
      2.314 +/- 1.399 mg/L vs. 0.790 +/- 0.423 mg/L, P = 0.0002; and coronary artery
      disease: healthy control, 1.232 +/- 0.601 mg/L vs. 0.790 +/- 0.423 mg/L, P =
      0.0113). Besides, there were close correlations between plasma D-dimer and hs-CRP
      in overall (Y = 4.8798X + 0.8138, r2 = 0.4497, r = 0.671, P < 0.001), aortic
      dissection (Y = 2.6298X + 1.2098, r2 = 0.5762, r = 0.759, P < 0.001), and aortic
      aneurysm (Y = 7.1341X + 1.3006, r2 = 0.4935, r = 0.7025, P = 0.048) groups rather
      than in the coronary artery disease or healthy control subjects. In addition,
      there were no significant differences between D-dimer and hs-CRP values of the
      aortic supernatant among groups except for undetectable D-dimer in the aortic
      supernatant of the coronary artery disease group. CONCLUSIONS: The patients with
      acute aortic dissection and aortic aneurysm may reflect the extensive
      inflammatory reaction and severe coagulopathies in the patients with acute type A
      aortic dissection, and thoracic aortic aneurysm in comparison to the coronary
      patients and healthy control individuals. The detections after onset in the
      patients with acute chest pain may help making a differential diagnosis between
      the aortopathies and ischemic heart disease. The scanty significance of the
      tissue biomarkers may preclude their diagnostic value in clinical practice.

PMID- 22358273
TI  - Assessment of noninvasive ventilation with two levels of positive airway pressure
      in patients after cardiac surgery.
AB  - INTRODUCTION: The application of two levels of ventilation by positive pressure
      (BiPAP(r)) associated with conventional respiratory therapy (CRT) in
      postoperative periord of cardiac surgery may contribute to reduction of pulmonary
      complications. OBJECTIVES: To evaluate the safety and compliance of preventive
      application of BiPAP(r) CRT associated with immediate postoperative myocardial
      revascularization. METHODS: 26 patients undergoing coronary artery bypass
      grafting were randomly allocated in one of the groups. Patients of the Control
      Group (CG) were treated only with conventional respiratory therapy, compared to
      BiPAP group (BG) (in addition to conventional respiratory therapy the patients
      were subjected to 30 minutes of ventilation by two levels twice a day). The
      conventional respiratory therapy was held in both groups, twice a day. All
      patients were evaluated for vital capacity, airway permeability, maximal
      respiratory pressures, oxygen saturation, heart rate, respiratory frequency,
      Volume Minute, tidal volume, systolic and diastolic blood pressure. Evaluations
      were performed during hospitalization preoperatively, immediately after
      extubation, 24h and 48h after extubation. RESULTS: In CG 61.5% of patients had
      some degree of atelectasias, in comparison to 54% of BG (P=0.691). The vital
      capacity was higher in the GB postoperatively (P<0.015). All the other
      ventilometric, gasometric, hemodynamic and manometric parameters were similar
      between groups. CONCLUSION: Coronary artery bypass grafting leads to
      deterioration of respiratory function postoperatively, and the application of
      positive pressure ventilation (BiPAP(r)) may be beneficial to restore lung
      function more quickly, especially vital capacity, safely, and well accepted by
      patients due to greater comfort with the sensation of pain during the execution
      of respiratory therapy.

PMID- 22358274
TI  - Transcutaneous electrical nerve stimulation after coronary artery bypass graft
      surgery.
AB  - INTRODUCTION: After cardiac surgery, patients have a limitation in respiratory
      muscle strength, which favors the appearing of pulmonary complications.
      OBJECTIVE: To evaluate the effectiveness of transcutaneous electrical nerve
      stimulation (TENS) on the painful process and respiratory muscle strength in
      patients undergoing coronary artery bypass graft (CABG). METHODS: The study
      included patients after on-pump CABG through sternotomy, general anesthesia,
      without being under the influence of neuromuscular blockade, with use of chest
      and mediastinal tubes, and extubation within 6 hours after the procedure and
      presenting index equal to or greater than three visual analog scale (VAS) of pain
      being on the first day after surgery. We recruited 20 patients divided into two
      groups with no predominance of sex: the control group (n = 10), who received more
      physiotherapy analgesic therapy, and TENS group received analgesic therapy,
      physiotherapy and TENS. The TENS was applied for 30 minutes, three times a day, a
      3-hour period each application. RESULTS: For the degree of pain, there was an
      average start and end, respectively, 7.0 / 1.0 for the TENS group and 7.0 / 8.0
      for the control group. For inspiratory muscle strength, - 102.5 cmH2O / - 141.17
      cm H2O to the TENS group and - 97.0 cmH2O / - 100.3 cm H2O for control. The
      expiratory muscle strength, 63cmH2O/125 cmH2O for the TENS group and 55.3
      cmH2O/53, 2 cmH2O for the control group. CONCLUSIONS: TENS has shown significant
      effectiveness in reducing pain, and the increase in respiratory muscle strength
      at first-day after CABG surgery.

PMID- 22358276
TI  - Coronary dominance patterns in hypoplastic left heart syndrome.
AB  - INTRODUCTION: Although hypoplastic left heart syndrome (HLHS) be extensively
      studied, this disease still has a high mortality rate compared to other diseases
      treated as univentricular physiology. In this way, morphological differences
      between phenotypes within the spectrum of HLHS may be risk factors and their
      identification can assist in choosing treatment between subgroups. OBJECTIVE: To
      identify the most prevalent form of coronary artery dominance in hearts with HLHS
      groups with mitral atresia (MA) and mitral stenosis (MS). METHODS: Analysis of
      coronary anatomy according to the distribution of epicardial branches and the
      pattern of dominance, classified as right, left or balanced. The control group
      was composed of nine pieces of morphologically normal hearts, the HLHS group
      consisted of 9 pieces with MA and 24 pieces with MS. For statistical analysis we
      used the x2 test. RESULTS: There were significant differences between the two
      groups in relation to coronary artery dominance (x2 = 9.298, P = 0.01). Left
      dominance was present in 75% of cases of MS, and balanced one was only observed
      in pieces with MS. The control group had right dominance in all cases (P <0.01).
      CONCLUSIONS: Left dominance is more common in HLHS than in the control group of
      normal hearts and in HLHS. The left coronary dominance is more frequent in the
      subgroup with mitral stenosis.

PMID- 22358275
TI  - SjO2/SvO2 correlation during pediatric cardiac surgery with cardiopulmonary
      bypass.
AB  - OBJECTIVES: To compare the SjO2 (cerebral oxygenation indicator) and SvO2
      (cardiac output indicator) during pediatric cardiac surgery with cardiopulmonary
      bypass (CPB). METHODS: Retrospective study. Data of SjO2 and SvO2 measured
      simultaneously at critical time periods during cardiac surgery with CPB were
      analyzed by the Spearman correlation test and Bland- Altman plot. RESULTS:
      Regression analysis of the pooled data showed poor correlation between SjO2 and
      SvO2 (r2=0.14, P=0.03) and Bland- Altman plot had a high bias (-7.9), indicating
      independency of the two variables. SjO2<50% (indicative of cerebral ischemia
      hypoxia) were observed in 50% of the measurements after rewarming during
      hypothermic CPB. CONCLUSIONS: SvO2 is not a good predictor of SjO2 during
      pediatric cardiac surgery with CPB, and low SjO2 can be undetected measuring SvO2
      only.

PMID- 22358277
TI  - Retrograde autologous priming in cardiopulmonary bypass in adult patients:
      effects on blood transfusion and hemodilution.
AB  - INTRODUCTION: Retrograde autologous priming (RAP) is a cardiopulmonary bypass
      (CPB) method, at low cost. Previous studies have shown that this method reduces
      hemodilution and blood transfusions needs through increased intra-operative
      hematocrit. OBJECTIVE: To evaluate RAP method, in relation to standard CPB
      (crystalloid priming), in adult patients. METHODS: Sixty-two patients were
      randomly allocated to two groups: 1) Group RAP (n = 27) of patients operated
      using the RAP and; 2) Control group of patients operated using CPB standard
      crystalloid method (n = 35). The RAP was performed by draining crystalloid prime
      from the arterial and venous lines, before CPB, into a collect recycling bag. The
      main parameters analyzed were: 1) CPB hemodynamic data; 2) Hematocrit and
      hemoglobin values; 3) The need for blood transfusions. RESULTS: It was observed
      statistically significant fewer transfusions during surgery and reduced CPB
      hemodilution using RAP. The CPB hemodynamic values were similar, observing a
      tendency to use lower CPB flows in the RAP group patients. CONCLUSION: This
      investigation was designed to be a small-scale pilot study to evaluate the
      effects of RAP, which were demonstrated concerning the CPB hemodilution and blood
      transfusions.

PMID- 22358278
TI  - Skeletonized internal thoracic artery is associated with lower rates of
      mediastinitis in elderly undergoing coronary artery bypass grafting surgery.
AB  - BACKGROUND AND OBJECTIVES: Mediastinitis is a serious complication of median
      sternotomy and is associated to significant morbidity and mortality. The aim of
      this study is to identify which option of harvesting internal thoracic artery
      (ITA), pedicled or skeletonized, is associated with lower rates of mediastinitis
      after coronary artery bypass grafting surgery (CABG) in elderly, in the Division
      of Cardiovascular Surgery of PROCAPE. METHODS: Retrospective study of 160 elderly
      who underwent consecutive CABG between May 2007 and June 2011. Eleven
      preoperative variables, four intraoperative variables and eight postoperative
      variables possibly involved in the development of postoperative mediastinitis
      were evaluated between two groups: CABG with skeletonized ITA (n=80) and pedicled
      ITA (n=80). Univariate and multivariate logistic regression analyses were
      applied. RESULTS: The incidence of mediastinitis was 6.8% (n=11), with a
      lethality rate of 54.5% (n=6). The skeletonized ITA group were more exposed than
      pedicled ITA group to obesity (n=12 vs. n=4; 15% vs. 5%; P=0.035) and multiple
      transfusions (n=25 vs. n=11; 31.2% vs. 13.7%; P=0.008). The pedicled ITA group
      presented a greater risk of mediastinitis after CABG than skeletonized ITA group
      (n=10 vs. n=1; 12.5% vs. 1.2%; Unadjusted OR 11.3; 95% CI 1.4 - 241.5; P=0.008).
      In multivariate analysis, this difference maintained statistically significant
      (Adjusted OR 5.2; 95% CI 1.5-495.8; P=0.012), being considered an independent
      association. CONCLUSIONS: We suggest that elderly should be considered for
      strategies to minimize risk of infection. In elderly that undergo unilateral ITA,
      the problem seems to be related to how ITA is harvested. Elderly should always be
      considered for use of skeletonized ITA.

PMID- 22358279
TI  - Risk factors for sternal wound infections and application of the STS score in
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Sternal wound infection (SWI) after coronary artery bypass graft
      (CABG) surgery is a major complication. Identifying patients at risk of SWI is
      essential for the application of preventive measures. OBJECTIVE: To identify the
      pre- and intra-operative risk factors, apply the STS risk score and determine the
      correlation between the risk score and microorganisms isolated from surgical
      wounds in a Brazilian hospital. METHODS: This is a retrospective analysis of a
      database of all CABG surgeries performed in a single institution from 2006 to
      2008. Chi-square analysis was used for categorical variables and Student's t-test
      was used for quantitative variables. Multivariate logistic regression model was
      used to identify independent risk factors for SWI. P <0.05 was considered
      significant. RESULTS: The infection rate was 7.2% (143/1975). The multiple
      regression analysis found the following risk factors: female gender (OR 2.06;
      95%CI 1.40-3.03; P<0.001), BMI>40 kg/m2 (OR 6.27, 95%CI 2.53-15.48; P<0.001),
      diabetes (OR 2.33; 95%CI 1.56-3.49; P<0.001), number of affected coronary
      arteries (OR 7.78; 95%CI 1.04-57.79; P<0.001) and use of bilateral internal
      thoracic artery (OR 3.85; 95%CI 2.10-7.07; P<0.001). Infected patients had a mean
      score of 9, whereas non-infected patients had a mean score of 7 (P<0.001). There
      was no correlation between microorganisms, scores and risk factors. CONCLUSION:
      Female gender, diabetes, BMI>40 kg/m2, number of affected coronary arteries and
      use of bilateral internal thoracic artery were associated with a higher risk of
      infection. The STS risk score can be successfully used and there was no
      correlation between microorganisms, the score and risk factors at our
      institution.

PMID- 22358280
TI  - Non Working Beating Heart: a new strategy of myocardial protection during heart
      transplant.
AB  - BACKGROUND AND OBJECTIVE: We attempt to reduce the ischemic time during
      implantation of the donor heart in the bicaval bipulmonary orthotopic position
      using normothermic beating heart and thus, facilitate the transplanted heart
      adaptation to the recipient. This study presents a small experience about a new
      strategy of myocardial protection during heart transplant. METHODS: In
      cardiopulmonary bypass, the aorta anastomosis was done first, allowing the
      coronary arteries to receive blood flow and the recovering of the beats. The rest
      of the anastomosis is performed on a beating heart in sinus rhythm. The pulmonary
      anastomosis is the last to be done. This methodology was applied in 10 subjects:
      eight males, age 16-69 (mean 32.7 years), SPAo 90-100 mmHg (mean 96 mmHg), SPAP
      25-65 mmHg (mean 46.1 mmHg), PVR 0.9 to 5.0 Wood (mean 3.17 Wood), GTP 4-13 mmHg
      (mean 7.9 mmHg), and eight male donors, age 15-48 years (mean 27.7 years), weight
      65-114 kg (mean 83.1 kg). Causes of brain coma: encephalic trauma in five
      hemorrhagic stroke in four, and brain tumor in one. RESULTS: The ischemic time
      ranged from 58-90 minutes (mean 67.6 minutes) and 8 donors were in hospitals of
      Sao Paulo and two in distant cities. All grafts assumed the cardiac output
      requiring low-dose inotropic therapy and maintained these conditions in the
      postoperative period. There were no deaths and all were discharged. The late
      evolution goes from 20 days to 10 months with one death occurred after 4 months
      due to sepsis. CONCLUSION: This method, besides reducing the ischemic time of the
      procedure, allows the donated organ to regain and maintain their beats without
      pre or after load during implantation entailing the physiological recovery of the
      graft.

PMID- 22358282
TI  - Respiratory physiotherapy and its application in preoperative period of cardiac
      surgery.
AB  - Cardiac surgical procedures change respiratory mechanics, defecting in lung
      dysfunction. The physical therapists play an important role in the preparation
      and rehabilitation of individuals who are undergoing cardiac surgery, as they
      have a large quantity of techniques. The objective was to evaluate the
      effectiveness of breathing exercises with and without the use of devices, and
      respiratory muscle training in preoperative period of cardiac surgery in reducing
      postoperative pulmonary complications. Although there are controversies as to
      which technique to use, studies show the effectiveness of preoperative
      physiotherapy in the prevention and reduction of postoperative pulmonary
      complications.

PMID- 22358281
TI  - Gene therapy for ischemic heart disease: review of clinical trials.
AB  - Severe ischemic heart disease with refractory angina, occurs in increasing
      incidence. Alternative forms of treatment, in an attempt to reduce myocardial
      ischemia and relief of symptoms has been studied. In this context, gene therapy
      is an option, for the possibility of inducing angiogenesis, establish collateral
      circulation and reperfuse ischemic myocardium. Several clinical trials have been
      conducted and, except for specific cases of adverse effects, there is indication
      of safety, feasibility and potential effectiveness of therapy. The clinical
      benefit, however, is not yet well established. In this article we review the
      clinical trials of gene therapy for patients with ischemic heart disease. The
      approach includes: (1) myocardial ischemia and angiogenesis on the
      pathophysiological aspects involved, (2) growth factors, dealing with specific
      aspects and justifying the use in cardiac patients with no option for
      conventional therapy, (3) controlled clinical trials, where a summary of the main
      studies involving gene therapy for severe ischemic heart disease is presented,
      (4) our experience, especially on preliminary results of the first gene therapy
      clinical trial in Brazil and (5) future prospects.

PMID- 22358283
TI  - Reflections on the 24 years durability of an isolate tricuspid bovine pericardium
      IMC/Braile bioprosthesis.
AB  - We were challenged by the experience of one patient reoperation for a
      bioprosthetic bovine pericardium degenerative stenosis, 24 years after
      implantation. This bioprosthesis was implanted due to tricuspid valve bacterial
      staphylococcal endocarditis after septic abortion.

PMID- 22358284
TI  - Surgical treatment of lone atrial fibrillation by mid-sternotomy Maze procedure
      under standard cardiopulmonary bypass.
AB  - The aim of article is to give a brief description to the surgical strategies for
      patients with lone atrial fibrillation without associated cardiac operations, and
      present the possible indications of on-pump Maze procedures through a mid
      sternotomy approach.

PMID- 22358285
TI  - Giant ventricular myxoma obstructing right ventricular outflow tract.
AB  - Intracardiac myxoma is predominantly located in the left atrium but their
      location in the right ventricle is quite unusual. We present a case in which
      successful excision of the tumor was done through bicameral approach.

PMID- 22358286
TI  - Coronary artery bypass graft surgery after acute myocardial infarction caused by
      thrombosis of coronary aneurysm.
AB  - The morphology of coronary aneurysm sets a predisposing factor to thrombus
      formation. However, the blood stasis caused by the change in flow may not be
      enough to cause thromboembolic events.

PMID- 22358287
TI  - Heart valve papillary fibroelastoma associated with cardioembolic cerebral
      events.
AB  - Papillary fibroelastomas of the heart valves are benign, slow-growing, rare
      tumors of the heart. This tumor represents a potential cause of systemic
      embolism, stroke, myocardial infarction and sudden death. Early diagnosis is very
      important, as surgical excision of these tumors can prevent cerebrovascular and
      cardiovascular complications. Diagnosis is usually made by transesophageal
      echocardiogram. We describe two cases of patients with papillary fibroelastomas
      causing cardioembolic cerebral events, which underwent successful surgical
      treatment. The authors present a brief review of the literature.

PMID- 22358288
TI  - Dr. Cid Nogueira: a medical pioneer of cardiac surgery in Brazil.

PMID- 22358289
TI  - Cid Nogueira.

PMID- 22358290
TI  - National impact.

PMID- 22358292
TI  - Cardiac resynchronization therapy.

PMID- 22358293
TI  - An overview of basic research articles recently published by Clinics.

PMID- 22358295
TI  - Many reasons to celebrate.

PMID- 22358294
TI  - Can we predict disease?

PMID- 22358296
TI  - Minimally invasive cardiac surgery in Brazil.

PMID- 22358297
TI  - Apology to the use of double mammary.

PMID- 22358298
TI  - Dissection of the internal thoracic artery using skeletonized technique.

PMID- 22358299
TI  - Surgical treatment of atrial fibrillation: incoherence or negligence?

PMID- 22358300
TI  - Characteristics of MDS patients seen at private practices differ significantly
      from those treated at university hospitals in Germany.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are mainly a disease of the elderly.
      Commonly, MDS patients are treated in an outpatient setting making
      hematological/oncological private practices (PP) an important backbone in the
      management of MDS patients. METHODS: To gain more insights into the
      characteristics of patients with MDS treated in hematological/oncological PP and
      to evaluate the daily diagnostic routines and classification systems used, we
      performed questionnaire-based analyses. Moreover, to investigate whether
      characteristics of MDS in PP differ from patients treated in specialized MDS
      centers in university hospitals (UH), we compared both cohorts of MDS patients.
      RESULTS: In total, 197 patients in PP and 165 patients in UH were enrolled.
      Patients in UH were significantly younger as compared to PP. Furthermore, in UH,
      a greater proportion of patients with international prognostic scoring system
      (IPSS) higher risk were found, whereas patients with IPSS lower risk were more
      frequent in PP. In addition, patients in UH had significantly lower hemoglobin
      levels and platelet counts compared to PP. CONCLUSION: Our data show that PP and
      UH are approached by different MDS patient cohorts resulting in different
      diagnostic workups of MDS patients.

PMID- 22358301
TI  - ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of
      Brazilian acute myeloid leukemia patients.
AB  - PURPOSE: Polymorphisms in the ABCB1 gene may influence P-glycoprotein (Pgp)
      expression and/or activity. Because the population in Brazil is markedly
      heterogeneous, we analyzed the relationship between ABCB1 polymorphisms and Pgp
      expression/activity in Brazilian acute myeloid leukemia (AML) patients. METHODS:
      Acute myeloid leukemia samples from 109 patients were studied. ABCB1 gene
      variants rs1128503 (C1236T) and rs1045643 (C3435T) were analyzed by PCR-RFLP
      assay. Pgp expression and Pgp activity were analyzed by flow cytometry. RESULTS:
      There was a similar distribution of Pgp expression and activity on polymorphisms
      C1236T, C1236C, and T1236T for exon 12, and C3435T, C3435C, and T3435T for exon
      26. An exception was observed in the lowest ratio of mean fluorescence intensity
      (MFI) median for Pgp expression in the TT genotype for both studied exons, and
      its correspondence to a low MFI median for Pgp activity. Pgp expression did not
      show impact on the response to remission induction therapy, but the MFI median of
      Pgp expression in the remission failure group was higher than that of the
      complete remission (CR) group of patients (p = 0.04). Overall survival (OS) was
      significantly influenced by CR (p = 0.0001). Better 5-year OS and 5-year event
      free survival rates (p = 0.04 and p = 0.007, respectively) were achieved in
      patients presenting the genetic variant CC in exon 12 followed by those
      presenting the variant CT in exon 26 (p = 0.001). CONCLUSIONS: Polymorphisms in
      the ABCB1 gene and the levels of Pgp expression could be useful to identify
      prognostic in AML patients.

PMID- 22358302
TI  - MDR1 gene C3435T polymorphism and cancer risk: a meta-analysis of 34 case-control
      studies.
AB  - BACKGROUND: P-glycoprotein, the product of the MDR1 gene, is a transmembrane
      active efflux pump for a variety of environmental toxins and xenobiotics.
      Epidemiological studies have evaluated the association between MDR1 C3435T
      polymorphism and cancer susceptibility. However, published data are still
      inconclusive. METHODS: To derive a more precise assessment of this relevance, we
      performed a meta-analysis, up to September 2010, of 5,196 cases with different
      cancer types and 6,827 controls from 34 published case-control studies. Summary
      odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for MDR1
      C3435T polymorphism and cancer were estimated using fixed- and random-effects
      models when appropriate. RESULTS: The overall results suggested that the variant
      was associated with a moderately increased cancer risk in all comparison models
      tested (OR = 1.26, 95% CI: 1.06-1.50 for TT vs. CC; OR = 1.19, 95% CI: 1.04-1.37
      for CT vs. CC; OR = 1.15, 95% CI: 1.01-1.32 for recessive model; OR = 1.21, 95%
      CI: 1.06-1.38 for domain model, and OR = 1.14, 95% CI: 1.04-1.26 for allele
      contrast). In the subgroup analysis by cancer types, significant associations
      were found in breast cancer (OR = 1.66, 95% CI: 1.24-2.21 for TT vs. CC; OR =
      1.44, 95% CI: 1.14-1.82 for recessive model; OR = 1.41, 95% CI: 1.10-1.81 for
      domain model; and OR = 1.31, 95% CI: 1.13-1.52 for allele contrast) and renal
      cancer (OR = 1.99, 95% CI: 1.37-2.90 for TT vs. CC; OR = 1.74, 95% CI: 1.25-2.42
      for domain model; OR = 1.43, 95% CI: 1.09-1.88 for recessive model; and OR =
      1.40, 95% CI: 1.17-1.68 for allele contrast). However, no significant
      associations were found in colorectal cancer, gastric cancer, and acute
      lymphoblastic leukemia for all genetic models. In the ethnicity subgroup
      analysis, a significant association with cancer among Caucasians was found under
      the dominant model, homozygote comparison, CT versus CC comparison, and allele
      comparison. CONCLUSIONS: In summary, this meta-analysis suggests that the MDR1
      C3435T polymorphism is associated with cancer susceptibility, increasing the risk
      of breast and renal cancer.

PMID- 22358303
TI  - The roles of surgery and EMA/CO chemotherapy regimen in primary refractory and
      non-refractory gestational trophoblastic neoplasia.
AB  - PURPOSE: To determine the characteristics and outcome of patients with refractory
      gestational trophoblastic neoplasia (GTN) after primary chemotherapy (CTx).
      METHODS: The outcome of low- and high-risk patients with refractory GTN (n = 14,
      37%) was compared to those with non-refractory GTN (n = 24, 63%). Methotrexate
      treatment was used for patients with low-risk disease and EMA/CO for patients
      with high-risk disease. RESULTS: Median follow-up time was 53 months (range 1-173
      months). All non-refractory patients and 11 refractory patients (79%) survived (p
      = 0.015). Factors related to resistance to primary CTx was age (p = 0.012),
      duration between causal pregnancy and initial treatment (p = 0.003), surgery (p =
      0.014), hCG level before CTx (p = 0.09) and half-life of hCG (p = 0.061). Six out
      of 10 low-risk refractory patients treated with EMA/CO regimen in the second-line
      setting had been followed by no evidence of disease. Nine of 38 (24%) patients
      underwent surgery (TAH +/- BSO) for GTN. All of the patients treated with surgery
      were in the non-refractory group, but none of refractory patients underwent
      surgery (p = 0.014). CONCLUSIONS: Surgery and EMA/CO regimen are one of the main
      factors that play a role in the management of refractory low-risk GTN.

PMID- 22358304
TI  - Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles.
AB  - The aim of this work is to prepare non-woven polypropylene (PP) textile
      functionalized with bioactive molecules in order to improve its anticoagulation
      and antibacterial properties. This paper describes the optimization of the
      grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated
      PP, the characterization of the modified substrates and the effect of these
      modifications on the in vitro biological response towards cells. Then, the
      immobilization of gentamicin (aminoglycoside antibiotic) and heparin
      (anticoagulation agent) has been carried out on the grafted samples by either
      ionic interactions or covalent linkages. Their bioactivity has been investigated
      and related to the nature of their interactions with the substrate. For
      gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction
      of 99% of the adhesion of Escherichia coli have been observed when gentamicin was
      linked by ionic interactions, allowing the release of the antibiotic. By
      contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the
      anticoagulant effect up to 35 min has been highlighted when heparin was
      covalently bonded on the substrate, by contact with the blood drop.

PMID- 22358305
TI  - Ingenol mebutate: an introduction.
AB  - The incidence of nonmelanoma skin cancer continues to increase. While surgical
      excision remains the mainstay of treatment, growing demand from patients for
      effective, tissue-sparing approaches with good cosmetic results has led to the
      development of novel therapeutic agents. Several studies have reported on the
      safety and efficacy of topical ingenol mebutate gel, a derivative of the plant
      Euphorbia peplus, in the treatment of actinic keratosis and superficial basal
      cell carcinoma. An understanding of the history, mechanism of action, and recent
      trial evidence for this emerging therapy can assist physicians in counseling
      patients on available treatment options and in selecting appropriate therapy.

PMID- 22358306
TI  - Laser management of acne scarring.
AB  - Acne scarring is often challenging to manage. Various laser treatments are
      helpful in addressing abnormal color and texture in order to improve the
      appearance of an acne scar. This paper will review the appropriate use and side
      effects of these laser treatments.

PMID- 22358307
TI  - Undergraduate education in radiology. A white paper by the European Society of
      Radiology.

PMID- 22358308
TI  - Neuropsychological performance in patients with subcortical stroke.
AB  - Vascular cognitive impairment (VCI) is characterized by cognitive compromise
      predominantly of executive dysfunction. OBJECTIVES: To assess cognitive functions
      in VCI, focusing on executive functions, to observe functional losses in relation
      to activities of daily living (ADLs) and to detect early symptoms prior to the
      onset of dementia. METHODS: We evaluated healthy subjects matched for gender,
      education and age to patients with diagnosis of subcortical vascular disease who
      had a stroke classified into three groups: 1) vascular lesions and no impairment;
      2) vascular cognitive impairment with no dementia (VCIND); 3) vascular dementia
      (VaD). RESULTS AND DISCUSSION: The performance on neuropsychological tests
      differed among groups, worsening with increased impairment level. The probable
      VaD group demonstrated impaired performance in memory, processing speed and
      verbal production, while the VCIND group showed attention deficits. CONCLUSION:
      Impairment in executive functions and difficulties in ADLs allow us to
      differentiate levels of impairment in groups of subcortical vascular disease.

PMID- 22358309
TI  - Comorbidities associated with epilepsy and headaches.
AB  - Comorbidities are often associated with chronic neurological diseases, such as
      headache and epilepsy. OBJECTIVES: To identify comorbidities associated with
      epilepsy and headaches, and to determine possible drug interactions. METHODS: A
      standardized questionnaire with information about type of epilepsy/headache,
      medical history, and medication was administered to 80 adult subjects (40 with
      epilepsy and 40 with chronic headache). RESULTS: Patients with epilepsy had an
      average of two comorbidities and those with headache of three. For both groups,
      hypertension was the most prevalent. On average, patients with epilepsy were
      taking two antiepileptic medications and those with headache were taking only one
      prophylactic medication. Regarding concomitant medications, patients with
      epilepsy were in use, on average, of one drug and patients with headache of two.
      CONCLUSIONS: Patients with chronic neurological diseases, such as epilepsy and
      headaches, have a high number of comorbidities and they use many medications.
      This may contribute to poor adherence and interactions between different
      medications.

PMID- 22358310
TI  - Frontal assessment battery in a Brazilian sample of healthy controls: normative
      data.
AB  - OBJECTIVE: To show data on the performance of healthy subjects in the Frontal
      Assessment Battery (FAB), correlating with gender, age, education, and scores in
      the Mini-Mental State Examination (MMSE). METHODS: Two hundred and seventy-five
      healthy individuals with mean age of 66.4 +/- 10.6 years-old were evaluated. Mean
      total FAB scores were established according to the educational level. RESULTS:
      Mean total FAB scores according to the educational level were 10.9 +/- 2.3, for
      one to three years; 12.8 +/- 2.7, for four to seven years; 13.8 +/- 2.2, for
      eight to 11 years; and 15.3 +/- 2.3, for 12 or more years. Total FAB scores
      correlated significantly with education (r=0.47; p<0.0001) and MMSE scores
      (r=0.39; p<0.0001). No correlation emerged between FAB scores, age, and gender.
      CONCLUSION: In this group of healthy subjects, the Brazilian version of the FAB
      proved to be influenced by the education level, but not by age and gender.

PMID- 22358311
TI  - Experimental encephalitis caused by Taenia crassiceps cysticerci in mice.
AB  - OBJECTIVES: To present the experimental model of neurocysticercosis (NCC) caused
      by Taenia crassiceps cysticerci, to describe the inflammatory process,
      susceptibility, or resistance of BALB/c and C57BL/6 mice to this infection, and
      to describe the host-parasite relationship. METHODS: The animals were
      intracranially inoculated with initial stage T. crassiceps cysticerci. They were
      euthanized at 7, 30, 60, and 90 days after the inoculation. Their encephala were
      removed for the histopathologic analysis, classification of the parasites, and
      inflammatory lesions. RESULTS: Experimental NCC was observed on both mice
      lineages. BALB/c mice presented inflammatory lesions with greater intensity,
      inducing necrosis on late stage parasites, and with an acute inflammation
      pattern, while C57BL/6 mice showed greater capability on provoking early necrosis
      in the cysticerci, which showed a chronic inflammation pattern. CONCLUSIONS: This
      experimental model induced NCC on mice with characteristic inflammation and
      lesions. C57BL/6 mice were able to induce precocious necrosis of the parasites
      presenting inflammatory lesions with lower intensity.

PMID- 22358312
TI  - Paroxysmal dystonia and neuromyelitis optica.
AB  - Paroxysmal dyskinesias (PD) are thought to be rare movement disorders. The
      overwhelming majority of reported cases are primary. Secondary PD has seen
      reported to occur in some conditions, mainly in multiple sclerosis and head
      trauma. The anatomic origin of the lesion is also rarely seen at the spinal cord.
      Our objective was to describe four patients with paroxysmal dystonia secondary to
      spinal lesions during the recovering phase of a neuromyelitis optica (NMO) bout.
      In the reviewed literature, we do not find any report of PD related to NMO.

PMID- 22358313
TI  - A differential ICT based molecular probe for multi-ions and multifunction logic
      circuits.
AB  - This paper presents anthraquinone and benzimidazole based hybrid molecular
      architect as the state of the art for multifunctional molecular logic circuits.
      The moleculator exhibits differential output behavior towards F(-), Zn(2+) and
      Cu(2+) ions to provide opportunities for elaboration of XOR, INHIBIT, XNOR, AND,
      OR, NOR, logic functions and their integrated logic functions half-adder, half
      subtractor and comparator within a single molecule. These integral logic
      functions can be reprogrammed by self-annihilation or by another additional input
      in the same cell. This single molecule behaves uniquely where different logic
      functions can be operated and reset by using different inputs and outputs.

PMID- 22358314
TI  - The effect of botulinum toxin A on fat graft survival.
AB  - BACKGROUND: Autologous fat grafting is a common procedure used in plastic surgery
      to correct soft tissue deficiency or depression deformity. However, absorption of
      grafted fat in the recipient area is unpredictable, and various methods for
      improving fat survival have been developed clinically. This study analyzed the
      changes and viability of injected fat in relation to the effects of botulinum
      neurotoxin type A (BoNTA). METHODS: Fat tissue was harvested from the pre-urinary
      bladder cavity of four Sprague-Dawley rats and processed using the Coleman
      technique. The experiment was performed on the backs of eight BALB/c-nu mice. The
      injection of free fat grafts was performed on the bilateral side of the back of
      each mouse. The one side (experimental) was treated with 0.5 ml of a free fat
      injection combined with 0.5 IU of BoNTA in 0.1 ml of saline. The other side
      (control) was treated with 0.5 ml of free fat injection combined with 0.1 ml of
      saline. The mice were killed after 9 weeks, and the injected fat grafts were
      explanted, after which the weight and volume were measured. Histologic study was
      performed with hematoxylin and eosin staining. Statistical analysis of the weight
      and volume from both sides, the histologic parameters, and cellular integrity was
      performed. CONCLUSION: A difference in the weight, volume, and histologic
      parameters of the injected fat grafts was observed. The BoNTA-treated side
      exhibited a significantly higher survival rate than the control side. The
      histologic examination of the fat grafts also demonstrated that the grade scale
      of cellular integrity was higher for the BoNTA-treated sides. Botulinum toxin A
      significantly reduces the level of fat graft resorption. Therefore, an injected
      fat graft can be used in conjunction with botulinum toxin A and offers better
      volumetric improvement. 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 at www.springer.com/00266.

PMID- 22358315
TI  - New developments in the trace analysis of organic water pollutants.
AB  - Challenging tasks, increasing demands, and new generations of powerful analytical
      instruments initiated considerable progress in aquatic environmental analysis and
      led to a considerable improvement of analytical performance during the last few
      years. The ever growing number of emerging pollutants is tackled by specific and
      highly sensitive analytical methods with detection limits of a few nanogram per
      liter and even lower. Wide-scope monitoring techniques and multiclass and
      multiresidue analysis allow for the simultaneous determination of hundreds of
      compounds. The high mass resolution capability and mass accuracy of advanced mass
      spectrometric instruments, i.e., time-of-flight (TOF) MS or Fourier transform
      (FT)-Orbitrap MS, enable combined target and non-target analysis, including the
      identification of metabolites and abiotic degradation products. This minireview
      highlights some of the most recent developments in the trace analysis of
      important organic water pollutants and focuses on some specific groups of
      emerging contaminants, i.e., pharmaceuticals, flame retardants, disinfection by
      products, surfactants, per- and polyfluorinated compounds, benzotriazoles, and
      benzothiazoles, as well as on the identification of transformation products and
      on non-target analysis. References were selected according to their exemplary and
      innovative character and to their practical relevance.

PMID- 22358318
TI  - A twelve-connected porous framework built from rare linear cadmium tricarboxylate
      pentamer.
AB  - A twelve-connected 3D metal-organic framework built from a rare linear
      Cd(5)(COOR)(12) pentamer with selective CO(2) uptake, has been prepared and
      characterized, together with a 2D framework based on a shorter linear
      Cd(3)(COOR)(6) trimer.

PMID- 22358317
TI  - Vitamin D2 from light-exposed edible mushrooms is safe, bioavailable and
      effectively supports bone growth in rats.
AB  - Widespread poor vitamin D status, a health risk for bone disease, increases the
      need for new food sources of vitamin D. Light-exposed edible mushrooms synthesize
      vitamin D(2). Bioavailability, safety, and efficacy of high levels of vitamin
      D(2) from mushrooms to support bone health was established in chronically fed
      growing rats. INTRODUCTION: Poor vitamin D status from reduced sun exposure is
      made worse by limited access to vitamin D-containing foods. Exposing white button
      mushrooms to ultraviolet B (UVB) light markedly increases their vitamin D(2)
      content, creating a new food source of vitamin D. We used a growing rat model to
      determine safety, bioavailability, and efficacy in support of bone growth by
      vitamin D(2) from UVB-exposed mushrooms. METHODS: We fed 150 weanling female rats
      one of five diets for 10 weeks, all formulated on AIN-93 G. Control diets
      contained no mushrooms either with or without vitamin D(3). Other diets contained
      2.5% and 5.0% of UVB-exposed or -unexposed mushrooms. Safety of the high levels
      of vitamin D(2) from mushrooms was assessed by animal growth and by Von Kossa
      staining for soft tissue calcification. Bioavailability was determined from
      changes in circulating levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid
      hormone (PTH). Efficacy in support of bone growth was determined from measures of
      femur bending properties, size, mineralization, and microarchitecture. RESULTS:
      Diets containing 2.5% and 5.0% light-exposed mushrooms significantly raised
      25(OH)D and suppressed PTH levels compared to control-fed rats or rats fed 5.0%
      mushroom unexposed to light. Microarchitecture and trabecular mineralization were
      only modestly higher in the light-treated mushroom-fed rats compared to the
      controls. Von Kossa staining revealed no soft tissue calcification despite very
      high plasma 25(OH)D. CONCLUSIONS: Vitamin D(2) from UVB-exposed mushrooms is
      bioavailable, safe, and functional in supporting bone growth and mineralization
      in a growing rat model without evidence of toxicity.

PMID- 22358316
TI  - QCT bone mineral density responses to 1 year of oral bisphosphonate after total
      knee replacement for knee osteoarthritis.
AB  - Bone mineral density (BMD) declined in more than half (53.7%) of post-total knee
      arthroplasty (TKA) patients (44 of the 82) after 1 year of oral bisphosphonate
      treatment, and that this decline was significant in bilateral TKA patients.
      INTRODUCTION: TKA has proven to be an extremely successful procedure in terms of
      improving ambulatory function. However, the effects of such improvements in
      ambulatory function and of bisphosphonate on axial BMD have not been established.
      The purpose of this study was to determine the effect of 1 year of oral
      bisphosphonate in postmenopausal patients that have undergone TKA and to identify
      factors related to BMD changes using lumbar spine quantitative computed
      tomography (QCT). METHODS: Eighty-two postmenopausal women that underwent primary
      TKA for knee osteoarthritis and who received once-weekly oral alendronate 70 mg
      for 12 months after TKA were enrolled. The effect of 1 year of oral
      bisphosphonate treatment post-TKA and the factors related to general lumbar spine
      BMD changes by using QCT were determined. RESULTS: Some 53.7% of patients (44 of
      the 82) experienced an average lumbar spine QCT BMD decline of -6 mg/ml (range 
      15 to -0.5 mg/ml) after 1 year of oral bisphosphonate treatment, whereas the
      remaining 38 patients (46.3%) experienced an average increase of 6.8 mg/ml (range
      0.6 to 15.7 mg/ml). Logistic and linear regression analysis showed that bilateral
      TKA was significantly related to a BMD decline (p < 0.05). Other factors, such
      as, age, body mass index, number of comorbidities, and Knee Society scores were
      not found to be significantly related to BMD response. CONCLUSIONS: BMD declined
      in more than half (53.7%) of the patients after bisphosphonate treatment, and
      that this decline was significant in bilateral TKA patients. We believe that
      reduced mobility during rehabilitation was probably responsible for these BMD
      reductions.

PMID- 22358319
TI  - Electrode kinetics at carbon electrodes and the density of electronic states.
AB  - Marcus-Hush theory relates the rate of electron transfer to the density of
      electronic states of the electrode material. Through use of a carbon
      microelectrode--for which the density of states is expected to vary as a function
      of potential--this predication is validated for graphitic materials by
      measurement of a variety of outer-sphere redox systems.

PMID- 22358320
TI  - Exploring microsolvation of the anesthetic propofol.
AB  - Propofol (2,6-diisopropylphenol) is a broadly used general anesthetic. By
      combining spectroscopic techniques such as 1- and 2-color REMPI, UV/UV hole
      burning, infrared ion-dip spectroscopy (IRIDS) obtained under cooled and isolated
      conditions with high-level ab initio calculations, detailed information on the
      molecular structure of propofol and on its interactions with water can be
      obtained. Four isomers are found for the bare propofol, while only three are
      detected for the monohydrated species and two for propofol.(H(2)O)(2). The
      isopropyl groups do not completely block the OH solvation site, but reduce
      considerably the strength of the hydrogen bonds between propofol and water. Such
      results may explain the high mobility of propofol in the GABA(A) active site,
      where it cannot form a strong hydrogen bond with the tyrosine residue.

PMID- 22358321
TI  - Water-wire catalysis in photoinduced acid-base reactions.
AB  - The pronounced ability of water to form a hyperdense hydrogen (H)-bond network
      among itself is at the heart of its exceptional properties. Due to the unique H
      bonding capability and amphoteric nature, water is not only a passive medium, but
      also behaves as an active participant in many chemical and biological reactions.
      Here, we reveal the catalytic role of a short water wire, composed of two (or
      three) water molecules, in model aqueous acid-base reactions synthesizing 7
      hydroxyquinoline derivatives. Utilizing femtosecond-resolved fluorescence
      spectroscopy, we tracked the trajectories of excited-state proton transfer and
      discovered that proton hopping along the water wire accomplishes the reaction
      more efficiently compared to the transfer occurring with bulk water clusters. Our
      finding suggests that the directionality of the proton movements along the charge
      gradient H-bond network may be a key element for long-distance proton
      translocation in biological systems, as the H-bond networks wiring acidic and
      basic sites distal to each other can provide a shortcut for a proton in searching
      a global minimum on a complex energy landscape to its destination.

PMID- 22358322
TI  - Small RNAs: Protecting a healthy circulation.

PMID- 22358323
TI  - Cell polarity: CPEB gets tight with junctions.

PMID- 22358324
TI  - Cell adhesion: FAK or talin: who goes first?

PMID- 22358330
TI  - Y-family DNA polymerases and their role in tolerance of cellular DNA damage.
AB  - The past 15 years have seen an explosion in our understanding of how cells
      replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA
      polymerases lie at the heart of this process, which is commonly known as
      translesion synthesis. This family of polymerases has unique features that enable
      them to synthesize DNA past damaged bases. However, as they exhibit low fidelity
      when copying undamaged DNA, it is essential that they are only called into play
      when they are absolutely required. Several layers of regulation ensure that this
      is achieved.

PMID- 22358331
TI  - Chromatin replication and epigenome maintenance.
AB  - Stability and function of eukaryotic genomes are closely linked to chromatin
      structure and organization. During cell division the entire genome must be
      accurately replicated and the chromatin landscape reproduced on new DNA.
      Chromatin and nuclear structure influence where and when DNA replication
      initiates, whereas the replication process itself disrupts chromatin and
      challenges established patterns of genome regulation. Specialized replication
      coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is
      a continuous process taking place throughout the cell cycle. If DNA synthesis is
      perturbed, cells can suffer loss of both genome and epigenome integrity with
      severe consequences for the organism.

PMID- 22358333
TI  - Reductive elimination pathway for homocysteine to methionine conversion in
      cobalamin-dependent methionine synthase.
AB  - Density functional theory has been applied to investigate the methyl transfer
      from methylcobalamin (MeCbl) cofactor to homocysteine (Hcy) as catalyzed by
      methionine synthase (MetH). Specifically, the S(N)2 and the reductive elimination
      pathways have been probed as the possible mechanistic pathways for the methyl
      transfer reaction. The calculations indicate that the activation barrier for the
      reductive elimination reaction (24.4 kcal mol(-1)) is almost four times higher
      than that for the S(N)2 reaction (7.3 kcal mol(-1)). This high energy demand of
      the reductive elimination pathway is rooted in the structural distortion of the
      corrin ring that is induced en route to the formation of the triangular
      transition state. Furthermore, the reductive elimination reaction demands the syn
      accommodation of the methyl group and the substrate over the upper face of the
      corrin ring, which also accounts for the high energy demand of the reaction.
      Consequently, the reductive elimination pathway for MetH-catalyzed methyl
      transfer from MeCbl to Hcy cannot be considered as one of the possible
      mechanistic routes.

PMID- 22358334
TI  - Cellular impact and selectivity of half-sandwich organorhodium(III) anticancer
      complexes and their organoiridium(III) and trichloridorhodium(III) counterparts.
AB  - Half-sandwich organorhodium(III) complexes and their trichloridorhodium(III)
      counterparts are potent anticancer agents that enhance the formation of reactive
      oxygen species and invoke a strong induction of apoptosis in leukemia cells. The
      antiproliferative activity towards human MCF-7 and HT-29 adenocarcinoma cells of
      novel nonintercalating complexes containing the 5-substituted phenanthroline
      ligands 5,6-dimethylphenanthroline, 5-chlorophenanthroline, and 5
      nitrophenanthroline (phen*) increases dramatically in the order [(eta(5)
      C(5)Me(5))IrCl(phen*)](CF(3)SO(3)) < [(eta(5)-C(5)Me(5))RhCl(phen*)](CF(3)SO(3))
      < mer-[RhCl(3)(DMSO)(phen*)] (DMSO is dimethyl sulfoxide). Improved activity was
      also achieved by attaching a cell-penetrating peptide to the dipyrido[3,2-a:2',3'
      c]phenazine (dppz) ligand of an organorhodium(III) complex. Whereas 5
      substitution led to significant improvements in the activity of the
      organoiridium(III) and trichloridorhodium(III) compounds in comparison with the
      parent phenanthroline complex, the IC(50) values of their organorhodium(III)
      counterparts remained effectively invariable. The high activities of the
      trichloridorhodium(III) complexes (IC(50) = 0.06-0.13 MUM) were accompanied by
      pronounced selectivity towards human cancer cells in comparison with immortalized
      HEK-293 cells. In contrast, [(eta(5)-C(5)Me(5))RhCl(5,6-Me(2)phen)](CF(3)SO(3))
      (phen is phenanthroline) was markedly more active towards BJAB lymphoma cells
      than ex vivo healthy leukocytes and caused an immediate decrease in cellular
      adhesion possibly associated with interactions with membrane proteins. Its dppz
      analogue invoked an initial increase in glycolysis to compensate for reduced
      respiration before inducing a delayed onset of cell death. Strong
      antimitochondrial activity with respiration impairment and release of cytochrome
      c was established for both complexes.

PMID- 22358332
TI  - PI3K signalling: the path to discovery and understanding.
AB  - Over the past two decades, our understanding of phospoinositide 3-kinases (PI3Ks)
      has progressed from the identification of an enzymatic activity associated with
      growth factors, GPCRs and certain oncogene products to a disease target in cancer
      and inflammation, with PI3K inhibitors currently in clinical trials. Elucidation
      of PI3K-dependent networks led to the discovery of the phosphoinositide-binding
      PH, PX and FYVE domains as conduits of intracellular lipid signalling, the
      determination of the molecular function of the tumour suppressor PTEN and the
      identification of AKT and mTOR protein kinases as key regulators of cell growth.
      Here we look back at the main discoveries that shaped the PI3K field.

PMID- 22358335
TI  - Cyclodextrins as growth controlling agents for enhancing the catalytic activity
      of PVP-stabilized Ru(0) nanoparticles.
AB  - Cyclodextrins act as growth controllers in the synthesis of PVP-stabilized Ru(0)
      nanoparticles, leading to enhancement of the catalytic activity in the
      hydrogenation of furfural.

PMID- 22358336
TI  - Protein-gold nanoclusters for identification of amino acids by metal ions
      modulated ratiometric fluorescence.
AB  - Here we report that the dual fluorescence emissions from protein-gold (Au)
      nanoclusters can greatly be modulated by metal ions and the resultant
      fluorescence ratiometric responses provide a novel sensory method for the
      identification of amino acids. The protein-gold (Au) nanoclusters were simply
      synthesized by the reduction of chloroauric acid with bovine serum albumin (BSA),
      which exhibit dual emissions: the blue at 425 nm from the oxides of BSA, and the
      red at 635 nm from Au nanoclusters. It has been demonstrated that different metal
      ions react with BSA-Au nanoclusters and thus greatly affect the two emissions in
      different ways by fluorescence enhancement or quenching. Interestingly, the
      addition of amino acids leads to fluorescence ratiometric changes through the
      interactions with the bound metal ions. When BSA-Au nanocluster probes modulated
      by four different metal ions were used together to construct a sensor array,
      different amino acids were clearly discriminated by the distinctive patterns of
      four ratiometric fluorescence responses. Results and methods reported here
      provide a unique strategy for the determination of amino acids.

PMID- 22358337
TI  - A comparative evaluation of the small leucine-rich proteoglycans of pathological
      human intervertebral discs.
AB  - PURPOSE: Proteoglycans are important to the functioning of the intervertebral
      disc. In addition to aggrecan there are the small leucine-rich proteoglycans
      (SLRPs). These are less common but in other locations their functions include
      collagen organisation, sequestering growth factors and stimulating inflammation.
      We have performed a comparative analysis of the SLRP core protein species present
      in intervertebral discs with various pathologies. METHODS: Eighteen
      intervertebral discs from patients with scoliosis (n = 7, 19-53 years),
      degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58
      years) were used in this study. Proteoglycans were dissociatively extracted from
      disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and
      lumican) assessed by Western blotting following deglycosylation with
      chondroitinase ABC and keratanase. RESULTS: Intact SLRP core proteins and a
      number of core protein fragments were identified in most of the discs examined.
      Biglycan and fibromodulin were the most extensively fragmented. Keratocan
      generally occurred as two bands, one representing the intact core protein, the
      other a smaller fragment. The intact core protein of lumican was detected in all
      samples with fragmentation evident in only one of the older scoliotic discs.
      Decorin was less obvious in the disc samples and showed little fragmentation.
      CONCLUSION: In this cohort of pathological intervertebral discs, fragmentation of
      certain SLRP core proteins was common, indicating that some SLRPs are extensively
      processed during the pathological process. Identification of specific SLRP
      fragments which correlate with disc pathology may not only help understand their
      aetiopathogeneses, but also provide biomarkers which can be used to monitor
      disease progression or to identify particular disc disorders.

PMID- 22358338
TI  - High-grade spondylolisthesis: gradual reduction using Magerl's external fixator
      followed by circumferential fusion technique and long-term results.
AB  - PURPOSE: To report the results of a cohort of patients treated with this
      technique high lighting radiological and functional outcomes, discussing also
      benefits arising from a gradual reduction procedure compared with other
      techniques. METHODS: We evaluated nine patients who have undergone high-grade
      listhesis reduction and circumferential fusion at our institution from 1988 to
      2006. Average length of follow-up was 11 years (5-19). Functional outcomes and
      radiological measurements were recorded and reported. RESULTS: Slip magnitude was
      reduced by an average of 2.9 grades (Meyerding classification). Slip angle
      improved by an average of 66% (p = 0.0001), lumbosacral angle by 47% (p =
      0.0002), sacral rotation by 51% (p = 0.0068) and sacral inclination by 47% (p =
      0.0055). At the latest follow-up 88.9% had achieved solid fusion. Post-operative
      10-point Visual Analogue Score (VAS) for back pain had improved by 70% (p <
      0.001) and that for leg pain by 76% (p < 0.001) compared with pre-operative
      score. Average postoperative Oswestry Disability Index for all patients was 8%
      (range 0-16%) and that for Low Back Outcome Scores was 56.6 (range 44-70). All
      components of Short Form 36 Health Survey were greater than 80%. Overall
      patients' expectations were met in 100%. CONCLUSIONS: This is an effective and
      safe technique which addresses the lumbosacral kyphosis and cosmetic deformity
      without the neurological complications which accompany other reduction and fusion
      techniques for high-grade spondylolisthesis.

PMID- 22358340
TI  - [Legal abortion: knowledge of the professionals and implications of public
      policies].

PMID- 22358339
TI  - Safety of fluoroscopy guided percutaneous access to the thoracic spine.
AB  - BACKGROUND: Fluoroscopy-guided percutaneous access to thoracic vertebrae is
      technically demanding due to the complex radiological anatomy and close proximity
      of the spinal cord, major vessels and pleural cavity. There is a trend towards
      computed tomography (CT) guidance due to a perceived reduction in the risk of
      spinal canal intrusion by instrumentation causing neurological injury. Due to
      limited access to CT guidance, there is a need for safe fluoroscopy-guided
      percutaneous access to the thoracic spine. PURPOSE: To evaluate the safety of a
      strict radio-anatomical protocol in avoiding access-related neurological
      complications due to tool misplacement in fluoroscopy-guided percutaneous
      procedures on the thoracic spine. METHOD: A combined two-surgeon prospective case
      series of 444 procedures (biopsy, vertebroplasty or kyphoplasty) covering all
      thoracic vertebral levels T1-T12. Clinical examination and routine observations
      were used to identify access-related complications including neurological,
      vascular and visceral injury using physiological parameters. RESULTS: No patient
      in our series was identified to have sustained a neurological deficit or
      deterioration of preoperative neurological status. CONCLUSION: Percutaneous
      access to the thoracic spine using fluoroscopic guidance is safe. The crucial
      step of the protocol is not to advance the tool beyond the medial pedicle wall on
      the anterior-posterior projection until the tip of the instrument has reached the
      posterior vertebral cortex on the lateral projection.

PMID- 22358341
TI  - [Women with polycystric ovary syndrome have a higher frequency of metabolic
      syndrome regardless of body mass index].
AB  - PURPOSE: To assess the prevalence of metabolic syndrome and of its defining
      criteria in women with polycystic ovary syndrome from the Brazilian Southeast,
      who were stratified according to body mass index and compared to ovulatory
      controls. METHODS: This was a cross-sectional study conducted on 332 women of
      reproductive age, who were divided into two groups: Control, consisting of 186
      women with regular menstrual cycles and ovulatory symptoms and without a
      diagnosis of polycystic ovary syndrome or other type of chronic anovulation, and
      the Polycystic ovary syndrome,Group, consisting of 146 women with a diagnosis of
      polycystic ovary syndrome (Rotterdam Consensus ASRM/ESHRE). Each group was
      stratified according to the body mass index, as follows: body mass index ( < 25
      >=25 and <30, and >= 30 kg/m2). The frequencies of metabolic syndrome and of its
      defining criteria and the clinical and hormonal characteristics (follicle
      stimulating hormone, total testosterone, dehydroepiandrostenedione sulfate) were
      analyzed. RESULTS: The frequency of metabolic syndrome was six times higher in
      the obese Polycystic ovary syndrome Group than among control women with the same
      body mass index (Control with 10.5 versus Polycystic ovary syndrome with 67.9%,
      p<0.01); twice higher in the Polycystic ovary syndrome Group with body mass index
      >= 25 and <30 kg/m2 (Control with 13.2 versus Polycystic ovary syndrome with
      22.7%, p<0.01), and three times higher in the Polycystic ovary syndrome Group
      with body mass index <25 kg/m2 (Control with 7.9 versus Polycystic ovary syndrome
      with 2.5%, p<0.01), compared to control women paired for the same body mass
      index. Regardless of the body mass index, women with polycystic ovary syndrome
      had a higher frequency of all the criteria defining metabolic syndrome.
      CONCLUSION: Women with polycystic ovary syndrome have higher frequency of
      metabolic syndrome and of its defining criteria regardless of the body mass
      index. Hyperinsulinemia and hyperandrogenism are important characteristics of the
      origin of these alterations, especially in obese women with polycystic ovary
      syndrome.

PMID- 22358342
TI  - [Importance of quality of life assessment in patients with endometriosis].
AB  - PURPOSE: The present study examined the relationship between some clinical
      variables and quality of life in a group of patients with endometriosis. METHODS:
      A total of 130 women seen at a multidisciplinary center specializing in
      gynecology endometriosis in 2008 participated in the study. This was a cross
      sectional study conducted with a convenience sample. The diagnosis of
      endometriosis was performed by biopsy according to the criteria of the American
      Society for Reproductive Medicine. The clinical and demographic data were
      collected from the patients' records. Pain intensity was assessed by a visual
      numerical scale (0-10), and data on the quality of life were collected using the
      SF-36. Data analysis consisted of descriptive and inferential statistical tests,
      Spearman correlation coefficient and Kruskal-Wallis test to compare scores
      between groups. Nonparametric tests were used for analysis because data were not
      normally distributed. RESULTS: The patients were 21 to 54 years of age or 34,
      standard diversion (SD)=6.56], 87% had a university degree, and 75% were married.
      Seventeen percent reported cases of endometriosis in the family. The average time
      of onset of symptoms was 4.5 years (SD=6.6), 63% of patients were in stage 3 or 4
      of endometriosis 36% of patients had severe or disabling dysmenorrhea and the
      average intensity of pain according to a visual numerical scale was of 5.6
      (SD=3.5). Results suggest that the staging of the disease did not determine the
      intensity of pain. The time of onset of symptoms also showed no relationship to
      pain intensity and SF-36 scores. On the other hand, the intensity of pain was
      associated with lower scores on some scales of the SF-36. CONCLUSION: Patients
      with endometriosis had lower scores of quality of life than the general
      population and lower than those of some other diseases.

PMID- 22358343
TI  - [Opinion of medical and law students of Federal University of Rio Grande do Norte
      about abortion in Brazil].
AB  - PURPOSE: To analyze and compare the knowledge and opinions of Law and Medical
      students regarding the issue of abortion in Brazil. METHODS: This was a cross
      sectional study involving 125 graduate students from the class of 2010. Of these,
      52 were medical students (MED group) and 73 law students (LAW group). A
      questionnaire was applied based on published research about the topic. Dependent
      variables were: monitoring the abortion debate, knowledge concerning situations
      where abortion is permitted under Brazilian law, opinion about situations that
      agree with extending legal permission to terminate pregnancy and prior knowledge
      of someone who has undergone induced abortion. Independent variables were: sex,
      age, household income and graduation course. STATISTICAL ANALYSIS: chi2 and
      Fisher's exact tests, with the level of significance set at 5%. RESULTS: Most
      interviewees reported monitoring the debate on abortion in Brazil (67.3% of the
      MED group and 70.2% of the LAW group, p>0.05). When assessing knowledge on the
      subject, medical students had a significantly higher percentage of correct
      answers than law students (100.0 and 87.5%, respectively; p=0.005) regarding the
      legality of abortion for pregnancies resulting from rape. Elevated percentages of
      correct responses were also recorded for both groups in relation to pregnancies
      that threaten the life of the mother (94.2 and 87.5% for MED and LAW groups,
      respectively), but without statistical significance. A significant percentage of
      respondents declared they were in favor of extending legal abortion to other
      situations, primarily in cases of anencephaly (68%), pregnancy severely harming
      the mother's physical health (42.1%) or that of the fetus in cases of severe
      congenital malformation (33.7%). CONCLUSION: Results showed a satisfactory
      knowledge on the part of law and medical school graduate students regarding the
      legality of abortion in Brazil, combined with a favorable trend towards extending
      legal permission to other situations not covered by the law. It is important to
      underscore the inclusion of this topic in the undergraduate curriculum and the
      development of inter-professional teaching strategies.

PMID- 22358344
TI  - [Effect of ipriflavone on Wistar rats and their litters].
AB  - PURPOSE: Evaluate the effects of ipriflavone during fetogenesis, since no studies
      have been conducted to assess its effect during this period. METHODS: 60 pregnant
      rats were divided randomly into four groups (n=15). G-control (1 mL of distilled
      water) and three groups treated intragastrically with ipriflavone from the 16th
      to the 20th post coitus (PC) day: G-300 (300 mg/kg), G-1,500 (1,500 mg/kg) and G
      3,000 (3,000 mg/kg). The animals were weighed, anaesthetized intraperitoneally
      with xylazine and ketamine at doses of 180 mg/kg and 10 mg/kg, respectively, and
      sacrificed by total exsanguination on the 21st day. A complete blood count was
      performed and serum cholesterol, triglycerides, AST, ALT, urea, creatinine, and
      glucose were determined in pregnant rats. After laparotomy, the liver, kidneys,
      adrenals, spleen and ovaries were removed and weighed; fetuses and placentas were
      also weighed to obtain the average weight of the litters. Four fetuses (two males
      and two females) were chosen at random for the determination of the length and
      weight of brain, liver, kidneys and lungs. STATISTICAL ANALYSIS: ANOVA followed
      by Dunnett's test. For raw data without normal distribution and homoscedasticity,
      we used the Kruskal-Wallis test followed by the Mann-Whitney test. Proportions
      were analyzed by the chi2 test (p<0.05). RESULTS: Triglyceride levels (mg/dL)
      were: Control-G (138.8+/-21.8), G-300 (211.2+/-63.9) G-1,500 (251.5+/-65.2) G
      3,000 (217.7+/-49.6); p<0.05. The body weight of fetuses (g) was: G-Control (male
      3.3+/-0.3; female 3.1+/-0.3), G-300 (male 3.4+/-0.2; female 3.1+/-0.4), G-1,500
      (male 3.5+/-0.3; female 3.2+/-0.3), G-3,000 (male 3.4+/-0.5; female 3.1+/-0.4).
      CONCLUSION: Ipriflavone did not cause maternal toxicity, but increased
      triglyceride levels and reduced hematocrit at higher doses. The body and organ
      weights of the fetuses did not change with dam treatment. There were no external
      malformations or fetal deaths.

PMID- 22358345
TI  - [Factors associated with duration of breastfeeding in children under six months].
AB  - PURPOSE: To describe the characteristics of mothers and children and to evaluate
      the factors associated with discontinuation of exclusive breastfeeding. METHODS:
      A cross-sectional study on infants under six months of age who attended the
      vaccination campaign in 2008. In the sample design, vaccination units were
      selected by drawing lots and infants were similarly selected later at each unit
      systematically. A semi-structured instrument was used for data collection,
      containing questions about children's nutrition and socio-demographic
      characteristics. We used Odds Ratio and the chi2 test for data analysis,
      accepting as the critical level p<0.05. RESULTS: The prevalence of breastfeeding
      for infants under 120 and 180 days of age was 89.5 and 85% respectively, and
      exclusive breastfeeding was 50.6 and 39.7% for infants less than 120 and 180 days
      of age, respectively. The factors most related to the abandonment of exclusive
      breastfeeding in infants under six months were maternal employment outside the
      home (OR=2.73; 95%CI=1.74-4.29) and use of pacifiers (OR=4.26; 95%CI=2.85-6.38).
      The mother being multiparous (OR=0.57; 95%CI=0.40-0.81) and receiving postpartum
      care in the public health care network (OR=0.55; 95%CI=0.39-0.79) represented
      protective factors against the practice of early cessation of breastfeeding.
      CONCLUSIONS: The prevalence of breastfeeding and exclusive breastfeeding in the
      municipality of Uberlandia is among the highest in the country and the factors
      most often associated with the practice of early weaning were maternal employment
      outside the home, offering pacifiers to the infants, receiving postpartum care in
      the private health sector, and primiparity.

PMID- 22358346
TI  - [Influence of prolonged maternal stay in maternal and perinatal outcomes of two
      series of patients with placenta previa].
AB  - PURPOSE: To compare the maternal and perinatal outcomes of patients with placenta
      previa, after the adoption of a prolonged maternal hospital stay, to those of a
      1991 series. METHODS: We performed a retrospective study comparing 108 cases of
      placenta previa hospitalized in the Maternity School Assis Chateaubriand,
      Universidade Federal do Ceara, during the period from 01/01/2006 to 12/31/2010,
      with those obtained in 1991, when 101 cases of the pathology were observed at our
      institution. The following maternal and perinatal data were collected: maternal
      age, parity, gestational age at delivery, mode of delivery, maternal stay length,
      Apgar scores at the 1st and 5th minutes, birth weight, adequacy of birth weight,
      neonatal length stay, maternal and neonatal morbidity and mortality rates
      (maternal, fetal, neonatal and perinatal). Statistical analysis was performed
      using the chi2 and Fisher's exact tests. The results were considered significant
      when p<0.05. RESULTS: In 1991, placenta previa was found in 1.13% of cases
      (101/8900). In the present study, the prevalence was 0.43% (108/24726). No
      maternal death was observed in either series. Regarding the study of 1991, the
      current patients were significantly younger, with lower parity, were hospitalized
      longer, had better Apgar scores at 1st and 5th minutes, and had longer neonatal
      hospitalization. Also, we identified reduction of fetal, neonatal and perinatal
      mortality. CONCLUSIONS: Perinatal outcomes in patients with placenta previa were
      significantly improved between 1991 and the years 2006 and 2010. However, we can
      not say whether this improvement was due to the prolonged maternal hospital stay.

PMID- 22358347
TI  - [Serum markers of inherited thrombophilia and antiphospholipid antibodies in
      pregnant women with previous history of severe pre-eclampsia].
AB  - PURPOSE: To determine the frequency and the association of serum markers for
      inherited and acquired thrombophilias in pregnant women with a history of severe
      pre-eclampsia in previous pregnancies. METHODS: Case-control study consisting of
      81 pregnant women with a history of severe pre-eclampsia in previous pregnancies
      (study group) and 32 women with no history of severe pre-eclampsia in previous
      pregnancies (control group). The presence of inherited thrombophilia and
      antiphospholipid antibodies was screened in both groups. We used the chi-square
      test with Yates correction to assess associations and calculate the relative
      risks. RESULTS: The presence of thrombophilia was detected in 60.0% of patients
      with a previous history of pre-eclampsia and in 6.0% of the control patients. A
      significant association was found between pre-eclampsia in a previous pregnancy
      and the presence of markers for hereditary thrombophilia/antiphospholipid
      antibodies (p<0.05). The relative risk to develop pre-eclampsia was found to be
      1.57 (1.34<RR<1.84) for pregnant women with antiphospholipid antibodies, 1.53
      (1.26<RR<1.86) for women with hereditary thrombophilia markers and 1.86
      (1.45<RR<2.38) considering the presence of hereditary thrombophilia and/or
      antiphospholipid antibodies. CONCLUSION: Women with serum markers for inherited
      or acquired thrombophilia showed a high relative risk to develop pre-eclampsia.

PMID- 22358348
TI  - Angina pectoris in patients with HIV/AIDS: prevalence and risk factors.
AB  - INTRODUCTION: The incidence of ischemic heart disease is higher in patients with
      HIV/AIDS. However, the frequency of angina pectoris in these patients is still
      not known. Literature about this subject is still scarce. OBJECTIVE: To evaluate
      the prevalence of angina pectoris and risk factors for coronary disease and to
      examine the association between traditional risk factors and HIV-related risk
      factors and angina pectoris. METHOD: An epidemiological cross-sectional study,
      analyzed as case-control study, involving 584 patients with HIV/AIDS. Angina
      pectoris was identified by Rose questionnaire, classified as definite or
      possible. Information regarding risk factors was obtained through a
      questionnaire, biochemical laboratory tests, medical records and anthropometric
      measures taken during consultations at AIDS treatment clinics in Pernambuco,
      Brazil, from June 2007 to February 2008. To adjust the effect of each factor in
      relation to others, multiple logistic regression was used. RESULTS: There was a
      preponderance of men (63.2%); mean ages were 39.8 years for men, 36.8 years for
      women. The prevalence of definite and possible angina were 11% and 9.4%,
      respectively, totaling 20.4%, with independent associations between angina and
      smoking (OR = 2.88; 95% CI: 1.69-4.90), obesity (OR = 1.62; 95% CI: 0.97-2.70),
      family history of heart attack (OR = 1.70; 95% CI: 1.00-2.88), low schooling (OR
      = 2.11; 95% CI: 1.24-3.59), and low monthly income (OR = 2.93; 95% CI: 1.18
      7.22), even after adjustment for age. CONCLUSION: This study suggests that angina
      pectoris is underdiagnosed, even in patients with medical monitoring, revealing
      lost opportunities in identification and prevention of cardiovascular morbidity.

PMID- 22358349
TI  - Role of hyaluronic acid and laminin as serum markers for predicting significant
      fibrosis in patients with chronic hepatitis B.
AB  - OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of
      serum HA and LN as serum markers for predicting significant fibrosis in CHB
      patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B
      and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined
      according to the Metavir scoring-system. The diagnostic performances of all
      indexes were evaluated by the receiver operating characteristic (ROC) curves.
      RESULTS: Serum HA and LN concentrations increased significantly with the stage of
      hepatic fibrosis, which showed positive correlation with the stages of liver
      fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were
      significant differences of serum HA and LN levels between F2-4 group in
      comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001),
      respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum
      HA for diagnosis of significant fibrosis, giving its sensitivity, specificity,
      PPV, NPV, LR+, LR- and AC of 84.2%, 83.3%, 90.6%, 73.5%, 5.04, 0.19 and 83.9,
      respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the
      sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9%, 80.0%, 87.2%,
      60.0%, 3.59%, 0.35% and 74.7, respectively. Combinations of HA and LN by serial
      tests showed a perfect specificity and PPV of 100%, at the same time sensitivity
      declined to 63.2% and LR+ increased to 18.9, while parallel tests revealed a good
      sensitivity of 94.7%, NPV to 86.4%, and LR- declined to 0.08. CONCLUSIONS: Serum
      HA and LN concentrations showed positive correlation with the stages of liver
      fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed
      good diagnostic performance, which would be further optimized by combination of
      the two indices. HA and LN would be clinically useful serum markers for
      predicting significant fibrosis in patients with chronic hepatitis B, when liver
      biopsy is contraindicated.

PMID- 22358350
TI  - Risk factors of renal scars in children with acute pyelonephritis.
AB  - OBJECTIVE: The aim of this study was to determine the association between
      previously documented risk factors such as recurrent pyelonephritis with the
      incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND
      METHODS: Children with acute pyelonephritis who were admitted to the Department
      of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this
      study. DMSA scans were obtained 4-6 months after the last episode of
      pyelonephritis in all patients. RESULTS: A total of 80 children with acute
      pyelonephritis were enrolled in this study. Most of them were girls (77.5%), with
      a median age of 12 months. Nearly half of the children (n = 44; 55%) had one or
      more renal scars. The distribution of gender, CRP level and leukocytosis did not
      differ significantly regarding the absence or presence of renal scars (p > 0.05).
      Most of the scars occurred in children who had presented with bilateral
      pyelonephritis (69.4% vs. 18.2%, p = 0.001). Most of the patients with renal
      scars had a positive history of vesicoureteral reflux (VUR) (75% vs.13.6%, p =
      0.001). The significant roles of recurrent pyelonephritis and presence of VUR
      were further confirmed by multivariate analysis. CONCLUSIONS: According to our
      findings, presence of VUR and recurrent pyelonephritis are independently
      associated with a higher incidence of renal scarring.

PMID- 22358351
TI  - Effects of Epstein-Barr virus on the development of dendritic cells derived from
      cord blood monocytes: an essential role for apoptosis.
AB  - OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpes virus,
      which can adapt and evade host immune defense. Dendritic cells (DCs) play a
      pivotal role in the initiation and maintenance of immune responses. This study
      investigated the effects of EBV on cord blood monocytes derived DCs (CBDC).
      METHODS: Monocytes were isolated from cord blood and cultured in medium
      containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8
      supernatant was added in monocytes culture medium for EBV infection at day 0.
      Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane
      potential (MMP) were detected by flow cytometry. The morphology was observed by
      Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor
      of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3,
      8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was
      changed in EBV-treated group. Chromatin condensation and DNA fragmentation were
      observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and
      caspase 9 activation were enhanced in the EBV-treated group. This was accompanied
      by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV
      treated group and compared to mock-infected group. CONCLUSION: These results
      suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC
      apoptosis in caspase-dependent manner with involvement of the mitochondrial
      pathway. This might help EBV to evade host immune responses to establish
      persistent infection.

PMID- 22358352
TI  - Durability of the first combined antiretroviral regimen in patients with AIDS at
      a reference center in Belo Horizonte, Brazil, from 1996 to 2005.
AB  - Finding a better first antiretroviral regimen is one of the strategies used to
      improve span and quality of life of HIV/AIDS patients. 891 patients were followed
      during 24 months or until interruption/abandonment of treatment, changing regimen
      or death. At the end of 6 months, 69% of the patients were still being treated
      with the first regimen, 54% at 12 months, 48% at 18 months and 39% at 24 months.
      AZT-3TC-EFV was the most prescribed regimen and with the lesser discontinuation.
      NNRTI regimens showed high effectiveness and durability compared to PI regimens.
      Irregular medication dispensation was the only risk factor for
      failure/interruption of treatment in multivariate analyses. Intolerance/adverse
      effects were mainly responsible for first regimen discontinuation, followed by
      abandonment/non-adherence and virologic failure. Results showed significant
      difference between causes of interruption of first HAART with higher percentage
      of intolerance/adverse effects with PI regimens and higher immunologic failure
      with NNRTI regimens. Even with the availability of more potent and tolerable
      drugs, lack of adherence to HAART and high level of adverse effects are still the
      most important barriers to prolonged success of treatment. This study adds
      relevant information about durability and effectiveness of HAART in the first
      decade of its use in Brazil.

PMID- 22358353
TI  - Epidemiological aspects of acquired immunodeficiency syndrome in older
      Brazilians: a comparative approach.
AB  - OBJECTIVES: To compare epidemiological aspects of young (15 to 49 years old) and
      older (more than 50 years old) AIDS patients. METHODS: We analyzed 511,633 AIDS
      cases notified to the Brazilian Ministry of Health in the period of 1980-2008
      looking at sex, age ranges, educational level and exposure category. Patients
      were divided into three age groups: under 15, from 15 to 49 and over 50 years
      old. Using a comparative approach, we analyzed data with regard to category of
      exposure, education (expressed in years of schooling), and sex ratio among
      younger (15-49) and older adults (over 50 years old). Time series data were log
      transformed and normalized, and the temporal trend was evaluated. RESULTS: AIDS
      incidence is increasing among people over 50 years old in Brazil, with those
      older than 50 being responsible for 9.64 % of AIDS cases. There was no
      significant difference between educational level and gender (p = 0.468), but
      there was a significant difference in exposure category with a lower proportion
      of injecting drug users amongst the older group. CONCLUSION: Based on this
      analysis over the last 10 years, the percentage of AIDS cases has increased
      almost three times among people over 50 years old when compared with the 15-49
      year-old group. Our findings suggest that public campaigns have to be specially
      targeted to the older segment of the population, aiming at heterosexual
      transmission.

PMID- 22358354
TI  - High prevalence of human bocavirus 1 in infants with lower acute respiratory
      tract disease in Argentina, 2007-2009.
AB  - Human bocavirus (HBoV) is a parvovirus whose association with respiratory disease
      is currently under investigation. OBJECTIVE: To determine HBoV prevalence in
      children with lower acute respiratory infection. METHODS: We investigated HBoV in
      433 nasopharyngeal aspirates collected in 2007-2009 from children 0 to 5 years
      old hospitalized with bronchiolitis or pneumonia in Cordoba, Argentina. RESULTS:
      The general prevalence of HBoV was 21.5% and the positive cases (HBoV+) were more
      frequent during winter and spring. The mean age of HBoV+ patients was 6.9 months,
      with 87.1% of the detections corresponding to infants less than 1 year old (among
      which the prevalence of HBoV was 26.3% in patients < 3 months of age, 22.1% in 3
      to 6 months, 25.3% in 6 to 9 months, and 18.8% in 9 to 12 months). The sequence
      analysis of the NP1 coding region of 15 isolates showed that all isolates from
      Cordoba were HBoV1 which exhibited a homology of nearly 100% both among
      themselves and with the originally discovered virus from 2005. CONCLUSION:
      Overall, our results indicate that HBoV is a significant pathogen that
      contributes to acute respiratory infection both on its own and during coinfection
      with other viruses.

PMID- 22358355
TI  - Characterization and sensitivity to antibiotics of bacteria isolated from the
      lower respiratory tract of ventilated patients hospitalized in intensive care
      units.
AB  - OBJECTIVE: This observational study described the characterization of bacteria
      isolated from the lower respiratory tract of ventilated patients hospitalized in
      intensive care units. The demonstration of isolated microorganism resistance to
      antibiotics and a time-trend analysis of infection comparing a 48-month period
      were also other objectives. METHOD: Semi-quantitative assays of 1254 samples
      taken from 741 ventilated patients were performed, while pathogens were
      identified using the Enterotube II assay and VITEK 2 Compact equipment. Bacterial
      resistance to antibiotics was assessed by the Kirby-Bauer disc diffusion method
      and time-trend analysis of infection was based on data recorded by hospital
      microbiology laboratories. RESULTS: The most prevalent isolated bacteria from the
      patient's lower respiratory tract were with Gram-negative bacteria (67.8%) mostly
      represented by: Acinetobacter spp. (25.2%), Pseudomonas spp. (18.3%) and
      Klebsiellas spp. (9.4%). Acinetobacter spp. showed moderate high to very high
      resistance to ceftriaxone (CRO), gentamicin (CN), amikacin (AK), meropenem (MRP),
      aztreonam (ATM) and piperacillin/tazobactam (TZP). Some isolates of Acinetobacter
      spp. resistant to colistin (CS) were identified in this patient population.
      Pseudomonas spp. and Klebsiella spp. were very highly resistant to
      ampicillin/sublactam (AMS) and with moderate or low resistance to CRO, ATM, MRP,
      AK, CN and TZP. A decrease in the Pseudomonas spp. prevalence rate was observed,
      whereas an increase in Acinetobacter spp. and Klebsiella spp. prevalence rates
      were observed in a 48-month period. CONCLUSION: This research corroborated that
      these nosocomial infections are a relevant medical problem in our context. The
      most prevalent bacterial infections in the lower respiratory tract of ventilated
      patients were by Acinetobacter spp., Pseudomonas spp. and Klebsiella spp. The
      panel of antibiotics used as preventive therapy was not the solution of
      infections and probably induced drug-resistance mechanisms in these isolated
      microorganisms.

PMID- 22358356
TI  - Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations
      in HBV-infected Chinese patients with persistently normal alanine
      aminotransferase and low serum HBV-DNA levels.
AB  - Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP)
      mutants in the patients with persistently normal alanine aminotransferase (ALT)
      and low serum HBV-DNA levels are unclear. The aim of this study was to determine
      HBV genotypes, precore and BCP mutations, and their association with chronic
      hepatitis and liver fibrosis in HBV-infected patients with persistently normal
      ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with
      normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real
      time PCR were included in this study. HBV genotypes were determined by real-time
      PCR. The precore and BCP mutations were detected by sequencing. All the patients
      had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%)
      were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%),
      and A1762T (6.7%). The prevalence of precore mutation was significantly higher in
      genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01).
      There was no significant difference in the prevalence of BCP mutations between
      genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that
      old age (> 40 years) and BCP mutations were independent predictors of liver
      necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver
      necroinflammation and fibrosis in patients with persistently normal ALT and low
      serum HBV-DNA levels in northeast China.

PMID- 22358357
TI  - Detection of genomic mutations in katG, inhA and rpoB genes of Mycobacterium
      tuberculosis isolates using polymerase chain reaction and multiplex allele
      specific polymerase chain reaction.
AB  - OBJECTIVE: Isoniazid (INH) and rifampin (RIF) are the most effective first line
      antibiotics against Mycobacterium tuberculosis. Mutations in several genes
      determine resistance of M. tuberculosis to INH, with the most common gene target
      of katG, and resistance to RIF is due to mutation in rpoB gene. The aim of
      present study was to assess the mutations in the regions related to RIF and INH
      resistance. METHODS: We characterized 80 clinical isolates of confirmed M.
      tuberculosis to analyze the most commonly observed INH and RIF mutations. PCR
      analysis and sequencing were used to detect mutations related to RIF and INH
      resistance. The multiplex allele-specific-PCR (MAS-PCR) was performed as a
      comparative assay and for evaluation of this method. RESULTS: The sequencing of
      the 250-bp region of katG codon 315, revealed point mutations at 5 different
      codons in 13.7% of the M. tuberculosis isolates. The sequencing of the 270-bp
      central region of the rpoB gene revealed point mutations at 7 different codons in
      12 (15%) of the M. tuberculosis isolates. The results obtained with MAS-PCR are
      in accordance with PCR-sequencing with high sensitivity and specificity for
      katG315, inhA15, and rpoB (531, 516, 526). CONCLUSION: The results of this study
      suggested that molecular techniques can be used as a rapid tool for the
      identification of drug resistance in clinical isolates of M. tuberculosis. Both
      DNA sequencing and MAS-PCR yielded high sensitivity for the detection of RIF and
      INH mutations and detecting multi-drug resistant tuberculosis cases.

PMID- 22358358
TI  - Gram-negative osteomyelitis: clinical and microbiological profile.
AB  - INTRODUCTION: Despite the growing interest in the study of Gram-negative bacilli
      (GNB) infections, very little information on osteomyelitis caused by GNB is
      available in the medical literature. OBJECTIVES AND METHODS: To assess clinical
      and microbiological features of 101 cases of osteomyelitis caused by GNB alone,
      between January 2007 and January 2009, in a reference center for the treatment of
      high complexity traumas in the city of Sao Paulo. RESULTS: Most patients were men
      (63%), with median age of 42 years, affected by chronic osteomyelitis (43%) or
      acute osteomyelitis associated to open fractures (32%), the majority on the lower
      limbs (71%). The patients were treated with antibiotics as inpatients for 40 days
      (median) and for 99 days (median) in outpatient settings. After 6 months follow
      up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and
      death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was
      isolated from 101 clinical samples. The most frequently isolated pathogens were
      Enterobacter sp. (25%), Acinetobacter baumannii (21%) e Pseudomonas aeruginosa
      (20%). Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for
      Pseudomonas aeruginosa and 60% for Acinetobacter baumannii. CONCLUSION:
      Osteomyelitis caused by GNB remains a serious therapeutic challenge, especially
      when associated to nonfermenting bacteria. We emphasize the need to consider
      these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial
      treatment can be administered since the very beginning of the therapy.

PMID- 22358359
TI  - Rational design of diagnostic and vaccination strategies for tuberculosis.
AB  - The development of diagnostic tests which can readily differentiate between
      vaccinated and tuberculosis-infected individuals is crucial for the wider
      utilization of bacillus Calmette-Guerin (BCG) as vaccine in humans and animals.
      BCG_0092 is an antigen that elicits specific delayed type hypersensitivity
      reactions similar in size and morphological aspects to that elicited by purified
      protein derivative, in both animals and humans infected with the tubercle
      bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a
      diagnostic test by using the predicted MHC class I epitopes. In addition, we
      performed a knockout of this gene by homologous recombination in the BCG vaccine
      strain to allow differentiation of vaccinated from infected individuals. For
      that, the flanking sequences of the target gene (BCG_0092)were cloned into a
      suicide vector. Spontaneous double crossovers, which result in wild type
      revertants or knockouts were selected using SacB. BCG_0092 is present only in
      members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I
      epitopes with potential for immunological diagnosis were defined, allowing the
      design of a specific diagnostic test. The strategy used to delete the (BCG_0092)
      gene from BCG was successful. The knockout genotype was confirmed by PCR and by
      Southern blot. The mutant BCG strain has the potential of inducing protection
      against tuberculosis without interfering with the diagnostic test based on the
      use of selected epitopes from BCG_0092.

PMID- 22358360
TI  - Expression of immunohistochemical markers in patients with AIDS-related lymphoma.
AB  - AIDS-related lymphomas (ARL) present high biological heterogeneity. For better
      characterization of this type of lymphoma, the objectives of the present study
      were to evaluate the expression of immunohistochemical markers of cell
      differentiation (CD10, Bcl-6, MUM-1) and determine cell origin profile according
      to Hans' classification of diffuse large B-cell lymphoma in AIDS patients. This
      study included 72 consecutive patients with ARL diagnosed at the University
      Hospital, Universidade Federal do Rio de Janeiro (UFRJ) and at the Brazilian
      Instituto Nacional de Cancer (INCA) from 2000 to 2006. The morphologic
      distribution of the lymphomas was the following: 61% were diffuse large B-cell
      lymphomas (DLBCLs), 15% were Burkitt's lymphomas, 13% were plasmablastic
      lymphomas, 10% were high-grade lymphomas and 1% was follicular lymphoma. The
      positivity for each immunohistochemical marker in DLBCLs, Burkitt's lymphoma and
      plasmablastic lymphoma was respectively: CD20, 84%, 100%, and 0; CD10, 55%, 100%,
      and 0; Bcl-6, 45%, 80%, and 0; MUM-1, 41%, 20%, and 88%. A higher positivity of
      CD20 (84% x 56%, p = 0.01) was found in DLBCL compared to non-DLBCL; in Burkitt's
      lymphomas a higher positivity of CD10 (100% x 49%, p = 0.04) and Bcl-6 (80% x
      39%, p = 0.035) were found compared to non-Burkitt's lymphomas. Germinal center
      (GC) profile was detected in 60% of DLBCLs. Our study suggests particular
      findings in ARL, as the most frequent phenotype was GC, different from HIV
      negative patients.

PMID- 22358361
TI  - In vitro activities of antifungal agents alone and in combination against
      fluconazole-susceptible and -resistant strains of Candida dubliniensis.
AB  - In the present study we used two groups of Candida dubliniensis strains: one
      containing fluconazole-susceptible clinical isolates and another containing
      fluconazole-resistant laboratory derivative from the former to examine the
      changes on susceptibility accompanying the development of resistance to
      fluconazole. Our findings confirmed the ability of C. dubliniensis isolates to
      become resistant to fluconazole and indicated that this resistance was crossed
      with ketoconazole, itraconazole, ravuconazole and terbinafine. We also tested
      combinations of terbinafine, amphotericin B, itraconazole and voriconazole
      against both groups of isolates in a checkerboard assay. Surprisingly, most
      combinations evidenced indifferent interactions, and the best synergism appeared
      when terbinafine and itraconazole were combined against the fluconazole-resistant
      group.

PMID- 22358362
TI  - Prevalence of antibodies to Borrelia burgdorferi sensu stricto in humans from a
      Cuban village.
AB  - Lyme disease has not been officially reported in Cuba. However, clinical cases
      have been serologically reported. Seroprevalence survey of Borrelia burgdorferi
      sensu stricto antibodies in humans in the country has not been conducted.
      OBJECTIVE: To estimate the prevalence of borrelial antibodies in inhabitants of a
      village with historically high level of tick infestation. METHODS: Serum
      specimens from 247 persons randomly selected from the population of the village
      were examined by IgG Western blot using B31 strain for estimating the prevalence
      of antibodies profile. RESULTS: A seroprevalence value interval (95% CI) of 0.6%
      7.2% was estimated for the studied population. The prevalent borrelial protein
      bands on immunoblots were 41, 72, 90/93, 34, 47, 60, 58, 56, 65/66 and 31 kDa in
      a decreasing order of significance. CONCLUSION: These results support the
      previous serological findings, suggesting the presence of this borreliosis in
      Cuba.

PMID- 22358363
TI  - Respiratory syncytial virus, infants and intensive therapy.
AB  - The aims of this study were to determine the presence of respiratory syncytial
      virus (RSV) and to assess the clinical features of the disease in infants with
      acute low respiratory tract infection hospitalized at pediatric intensive care
      units (PICU) of two university teaching hospitals in Sao Paulo State, Brazil.
      Nasopharyngeal secretions were tested for the RSV by the polymerase chain
      reaction. Positive and negative groups for the virus were compared in terms of
      evolution under intensive care (mechanical pulmonary ventilation, medications,
      invasive procedures, complications and case fatality). Statistical analysis was
      performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants
      were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients
      were previously healthy while 85.7% required mechanical pulmonary ventilation,
      20/21 patients presented with at least one complication, and the fatality rate
      was 14.3%. RSV positive and negative groups did not differ for the variables
      studied. Patients involved in this study were critically ill and needed multiple
      PICU resources, independently of the presence of RSV. Further studies involving
      larger cohorts are needed to assess the magnitude of the impact of RSV on the
      clinical evolution of infants admitted to the PICU in our settings.

PMID- 22358364
TI  - Tularemia and the oculoglandular syndrome of Parinaud.
AB  - An 18-year-old female came to our clinic with complaints of a tender lump just
      under her jaw on the left side and another lump in front of her left ear,
      ecchymosis around the eye and some redness in the eye at the same side. After
      administering antibiotic therapy for two days we suspected of tularemia and
      referred the patient to the Infectious Diseases Department. A serum sample was
      taken and a fine needle aspiration biopsy was performed. The patient was
      diagnosed with tularemia, the oculoglandular syndrome of Parinaud. Tularemia
      should also be kept in mind for differential diagnosis in patients with both
      ocular and glandular symptoms in endemic regions like Turkey and the appropriate
      therapy should be initiated immediately.

PMID- 22358365
TI  - Autoimmune features caused by dengue fever: a case report.
AB  - Dengue virus is the most important mosquito-borne viral disease in the world. Co
      circulation of the four types of dengue viruses and expansion of dengue epidemic
      gave rise to infection enhancement and a big expansion of clinical aspects of the
      disease. Herein we report a case of a 25-year-old white woman with dengue fever
      and numerous associated autoimmune features. Our patient had proteinuria, an
      extensive right pleural effusion, a thin pericardial effusion and ascites. She
      had a low C3 level and positive antinuclear antibody; cryoglobulins were also
      positive. The numerous autoimmune features of this patient were a diagnostic
      challenge, since she was a young woman and could be easily mistaken for a
      rheumatologic patient in a newly open disease. Dengue infection probably was a
      triggering event causing an abnormal immune response. Therefore, dengue should be
      suspected in patients with hematological disorders and autoimmune features in
      endemic regions or those who have travelled to those regions.

PMID- 22358366
TI  - Seronegative cat-scratch disease diagnosed by PCR detection of Bartonella
      henselae DNA in lymph node samples.
AB  - Cat scratch disease (CSD), the typical clinical manifestation of Bartonella
      infections usually follows a typical benign self-limited course. Nevertheless, a
      variety of unusual clinical manifestations and confusing imaging features can
      lead to misinterpretations and render the disease a diagnostic dispute. Routine
      laboratory tests exhibit varying reported sensitivity and are usually unhelpful
      in diagnosis, as serology fails in terms of specificity and/or sensitivity.
      Herein we report a case of seronegative Bartonella infection presenting as
      symptomatic suppurative lymphadenitis with abscess formation, which was
      surgically drained. Diagnosis was established by PCR analysis from lymph nodes
      samples obtained during the procedure. PCR detection of specific DNA fragments
      from lymph node biopsy provides a sensitive detection of disease. The technique
      should be considered for patients with suspected CSD and negative serology, since
      serological assays exhibit low sensitivity. In ambiguous cases, surgical
      exploration may provide tissue for diagnosis; it is well tolerated and affords
      improved recovery.

PMID- 22358367
TI  - Bacteroides fragilis endocarditis: a case report and review of literature.
AB  - Endocarditis due to Bacteroides fragilis is a rare disorder. This article
      describes a case of Bacteroides fragilis endocarditis associated with portal and
      superior mesenteric venous thrombosis in a patient without preexisting valvular
      heart disease and review the cases of endocarditis due to this anaerobic
      bacterium in medical literature since 1980.

PMID- 22358368
TI  - Molecular diagnosis and genotyping of Neisseria gonorrhoeae in urine samples from
      women at low-income communities in Rio de Janeiro, Brazil.

PMID- 22358369
TI  - Primary pneumococcal peritonitis in an immunocompetent child.

PMID- 22358370
TI  - Clinical investigation for infections caused by Enterobacteriaceae in intensive
      care unit of Anhui, China.

PMID- 22358371
TI  - Lagochilascariasis in a housecat and the potential risk for human disease.

PMID- 22358373
TI  - Identification of DNA-protein complexes using an improved, combined western
      blotting-electrophoretic mobility shift assay (WEMSA) with a fluorescence imaging
      system.
AB  - Electrophoretic Mobility Shift Assays (EMSAs) are used to detect DNA-protein
      interactions. With this type of assay it is difficult to distinguish between
      specific and non-specific DNA-protein complexes or to define which protein binds
      to the DNA. Here we describe a novel Western blot-combined EMSA (WEMSA) variant
      for a fluorescence imaging system which permits easy identification of specific
      DNA-protein-complexes. This method also allows investigation of several DNA
      protein complexes in parallel. We have identified and distinguished clearly
      between the SP1- and EGR1-DNA-protein complexes which exhibit overlapping binding
      to the GC-BOX of the mPGES-1 promoter.

PMID- 22358374
TI  - Plant regeneration and stable transformation in the floricultural plant Cleome
      spinosa, a C3 plant closely related to the C4 plant C. gynandra.
AB  - Cleome spinosa is widely used as a garden ornamental in many countries. Here we
      determined the optimal conditions for plant regeneration from different tissue
      explants grown in vitro. Induction medium containing MS salts, MS vitamins, 3%
      sucrose, 1 mg l-1 BA, 200 mg l-1 timentin, and 0.8% agar was sufficient for shoot
      regeneration of all the tissue explants examined, including leaf, hypocotyl, and
      cotyledon. Subsequently, an Agrobacterium tumefaciens-mediated method was
      developed to transform the vector pCHS, which carries the transgenes Petunia
      chalcone synthase (chs) and selection marker neomycin phosphotransferase II
      (nptII), into C. spinosa. From a total of 368 cotyledon explants, 13 putative
      transgenic lines were regenerated from selection medium supplemented with 50 mg l
      1 kanamycin and 200 mg l-1 timentin, and transferred to the greenhouse. Genomic
      PCR and Southern blot analyses revealed that the nptII transgene was present in
      all 13 transgenic plants. Similarly, when the Petunia chs transgene was used as a
      probe in Southern blot analysis, single or multiple hybridization bands were
      detected in 12 out of the 13 transgenic plants. In addition, T1 progeny assay
      from selected transformants showed that the nptII transgene can be transmitted in
      a Mendelian manner from transgenic parents into their progeny. This is the first
      report of stable transformation of the C3 dicotyledon C. spinosa, which will
      facilitate functional comparison of cell-type specific genes with counterpart C4
      dicotyledon C. gynandra using transgenic approaches.

PMID- 22358375
TI  - [Primary treatment for localized prostate cancer: evaluation of patients' quality
      of life].
AB  - BACKGROUND: Radical prostatectomy (RP) and percutaneous radiotherapy (RT) are
      viable options for the primary treatment of localized prostate cancer (PC). Given
      the comparable efficacy of both modalities quality of life (QOL) has been
      suggested as an additional decision criterion. In recent years several validated
      instruments have been introduced to assess QOL. Most of them allow for patient
      based rating of QOL. AIM: Herein, we aim to compare QOL after RP and RT in our
      own cohort of patients in Tubingen using validated questionnaires. METHODS: In
      total, 165 patients who had been treated for PC in Tubingen were enrolled. Of
      those 100 men had RP and 65 had RT. The validated QOL questionnaires EORTC QLQ
      C30 and EORTC QLQ-PR 25 were used for assessment. Statistical analyses focused on
      analyses of variance. RESULTS: Concordant to previous studies it could be shown
      that RP mainly creates voiding problems most importantly urinary incontinence but
      also erectile dysfunction. After RT, patients mainly complained about disturbed
      bowel function including diarrhea and proctitis as well as about urgency and
      frequency. RP patients had better PF2 Scale values than RT patients (p=
      0.00357143). On DI scales RT patients yielded significantly poorer values than
      the RP group (p= 0.003333). CONCLUSION: Our data comply well with those from
      other international centers. QOL is an important yet underestimated variable in
      oncological research. Our investigations underline the importance of an
      interdisciplinary approach for the successful management of PC.

PMID- 22358376
TI  - [Resection of metastases from prostate cancer].
AB  - Surgical resection of a solitary or a limited number of metastases is a
      controversy in patients with prostate cancer that is increasingly being
      discussed. The improved accuracy of the detection of local or distant recurrences
      after primary treatment using modern imaging techniques including choline PET/CT
      led to an increased demand for salvage surgical procedures. Apart from the
      resection of synchronous metastases at the time of radical prostatectomy the
      oncological efficacy of a salvage lymphadenectomy or a salvage resection of
      visceral or osseous metastases remains to be proven. Here, the available data
      covering the different clinical scenarios for the resection of metastases in
      prostate cancer and recommendations of recently published guidelines are
      reviewed.

PMID- 22358377
TI  - [Value of positron emission tomography in urological neoplasms: more form than
      substance?].
AB  - Positron emission tomography/computed tomography (PET/CT) is widely used for
      imaging urological neoplasms. This overview should help the urologist actively
      involved in oncology to assess the value of PET or PET/CT in each tumor entity.
      Besides prostate, testicular, renal, and bladder cancer less common urological
      malignancies like penile carcinoma and retroperitoneal masses are discussed.
      Differences in using PET/CT for primary diagnosis, staging, or restaging are
      outlined separately. Appropriate indications for the use in clinical practice are
      cited.

PMID- 22358378
TI  - Effect of proximal box elevation with resin composite on marginal quality of
      ceramic inlays in vitro.
AB  - OBJECTIVES: The objective of this study was to evaluate the marginal quality and
      resin-resin transition of milled CAD/CAM glass-ceramic inlays in deep proximal
      cavities with and without 3-mm proximal box elevation (PBE) using resin
      composites before and after thermomechanical loading. MATERIALS AND METHODS: MOD
      cavities with one proximal box beneath the cementoenamel junction were prepared
      in 48 extracted human third molars. Proximal boxes ending in dentin were elevated
      for 3 mm with different resin composites (RelyX Unicem, G-Cem, and Maxcem Elite
      as self-adhesive resin cements and Clearfil Majesty Posterior as restorative
      resin composite in one or three layers bonded with AdheSE) or left untreated. IPS
      Empress CAD inlays were luted with Syntac and Variolink II (n = 8). Marginal
      quality as well as the PBE-ceramic interface were analyzed under an SEM using
      epoxy resin replicas before and after thermomechanical loading (100,000 * 50 N
      and 2,500 thermocycles between +5 degrees C and +55 degrees C). RESULTS: Bonding
      glass-ceramic directly to dentin showed the highest amounts of gap-free margins
      in dentin (92%, p < 0.05). Bonded resin composite applied in three layers
      achieved 84% gap-free margins in dentin; PBE with self-adhesive resin cements
      exhibited significantly more gaps in dentin (p < 0.05). CONCLUSIONS: With a
      meticulous layering technique and bonded resin composite, PBE may be an
      alternative to ceramic bonding to dentin. Self-adhesive resin cements seem not
      suitable for this indication. CLINICAL RELEVANCE: For deep proximal boxes ending
      in dentin, a PBE may be an alternative to conventional techniques.

PMID- 22358379
TI  - The effect of zirconia sintering temperature on flexural strength, grain size,
      and contrast ratio.
AB  - OBJECTIVE: This study investigated the effect of sintering temperatures on
      flexural strength, contrast ratio, and grain size of zirconia. MATERIALS AND
      METHODS: Zirconia specimens (Ceramill ZI, Amann Girrbach) were prepared in
      partially sintered state. Subsequently, the specimens were randomly divided into
      nine groups and sintered with different final sintering temperatures: 1,300
      degrees C, 1,350 degrees C, 1,400 degrees C, 1,450 degrees C, 1,500 degrees C,
      1,550 degrees C, 1,600 degrees C, 1,650 degrees C, or 1,700 degrees C with 120
      min holding time. Three-point flexural strength (N = 198; n = 22 per group) was
      measured according to ISO 6872: 2008. The contrast ratio (N = 90; n = 10 per
      group) was measured according to ISO 2471: 2008. Grain sizes and microstructure
      of different groups were investigated (N = 9, n = 1 per group) with scanning
      electron microscope. Data were analyzed using one-way ANOVA with Scheffe test and
      Weibull statistics (p < 0.05). Pearson correlation coefficient was calculated
      between either flexural strength or contrast ratio and sintering temperatures.
      RESULTS: The highest flexural strength was observed in groups sintered between
      1,400 degrees C and 1,550 degrees C. The highest Weibull moduli were obtained for
      zirconia sintered at 1,400 degrees C and the lowest at 1,700 degrees C. The
      contrast ratio and the grain size were higher with the higher sintering
      temperature. The microstructure of the specimens sintered above 1,650 degrees C
      exhibited defects. Sintering temperatures showed a significant negative
      correlation with both the flexural strength (r = -0.313, p < 0.001) and the
      contrast ratio values (r = -0.96, p < 0.001). CONCLUSIONS: The results of this
      study showed that the increase in sintering temperature increased the contrast
      ratio, but led to a negative impact on the flexural strength. CLINICAL RELEVANCE:
      Considering the flexural strength values and Weibull moduli, the sintering
      temperature for the zirconia tested in this study should not exceed 1,550 degrees
      C.

PMID- 22358380
TI  - Expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) in human
      cholesteatoma.
AB  - Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein
      that functions as a pleiotropic regulator of many cellular processes including
      epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide
      phosphate oxidase complex which promotes formation of reactive oxygen species and
      degradation enzymes. RAC1 has been associated with rapid epithelial
      differentiation and invasive properties in human cholesteatoma. This study aimed
      to identify the presence of RAC1 in human cholesteatoma and analyze its
      functional role as a regulator of proteolysis and overgrowth. Tissue samples from
      human cholesteatoma and normal postaural skin were obtained from patients during
      otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by
      real-time RT-PCR, and localization of RAC1 expression was confirmed using
      immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of
      cholesteatoma was significantly elevated 2.94 fold on average, compared with
      normal control skin. RAC1 expression in the suprabasal and basal layer of
      cholesteatoma epithelium was stronger than normal control skin. Our results
      suggest that RAC1 can be associated with rapid epithelial differentiation and
      invasive properties of human cholesteatoma.

PMID- 22358381
TI  - The relationship between Th1/Th2 balance and 1alpha,25-dihydroxyvitamin D3 in
      patients with nasal polyposis.
AB  - We aimed to study Th1/Th2 cell balance by measuring the levels of cytokines IL-4,
      IL-10, and IFN-gamma, which play an important role in the immune response of
      patients with allergic rhinitis and/or nasal polyps, and determine the
      correlation between Th1/Th2 cell balance and 1alpha,25-dihydroxyvitamin D(3), an
      active metabolite of vitamin D. The study subjects were 60 adult patients and 40
      healthy volunteers. Subjects were separated into three groups: 30 patients
      diagnosed with nasal polyposis together with allergic rhinitis formed Group I, 30
      patients with nasal polyposis but without allergic rhinitis constituted Group II,
      and 40 healthy volunteers without nasal polyp and/or allergic rhinitis were the
      control group, or Group III. IFN-gamma, IL-4, IL-10, and total IgE levels were
      determined in the serum samples of all patients and vitamin D(3) in their plasma.
      A statistically significant difference was found between the Group I and the
      control group in their IgE, IL-4, IL-10, IFN-gamma, and vitamin D levels (p <
      0.05), while there were no such significant differences between Group II and the
      control group in these measurements (p > 0.05). Within Group I, vitamin D levels
      showed a negative correlation with IgE and IL-4 levels, and a positive
      correlation with IFN-gamma (p < 0.05). Within Group II, IgE levels showed a
      positive correlation with IL-4 and IL-10 levels (p < 0.05) and a negative
      correlation with IFN-gamma levels (p < 0.05). In this study, no significant
      relation was detected between vitamin D deficiency and nasal polyposis in the
      absence of allergic rhinitis. The study demonstrates that vitamin D is effective
      on Th1/Th2 balance in patients with allergic rhinitis and that there is a
      significant relation between vitamin D deficiency and allergy. These results are
      compatible with the possibility of an important role of vitamin D in the
      pathogenesis and degree of severity of allergic disease, and its capacity to
      control allergic disease.

PMID- 22358382
TI  - Stenting the nasopharyngeal isthmus by nasopharyngeal airway after correction of
      acquired total nasopharyngeal obstruction: surgical procedure and results.
AB  - The objective of this study is to describe a simple surgical procedure for
      management of acquired total nasopharyngeal obstruction in adults. Five patients
      were diagnosed as having complete nasopharyngeal obstruction over a 3-year
      period. Three patients previously underwent uvulopalatoplasty, while for the
      remaining two it was due to pharyngoscleroma. In all the patients, nasopharyngeal
      obstruction was at the level of the inferior edge of the soft palate. Two of the
      post-uvulopalatoplasty patients had recurrent obstruction after scar excision and
      topical application of mitomycin-C without stenting. All the patients were
      treated surgically by creation of a new anatomical nasopharyngeal isthmus and
      stenting it by nasopharyngeal airway for 6 months. All the patients experienced
      satisfactory results and good tolerability to airway placement. The
      nasopharyngeal airway can counteract the inevitable scar contraction of the new
      nasopharyngeal isthmus after surgical correction and maintain its patency.

PMID- 22358383
TI  - PLA2G4A mutants modified protective effect of tea consumption against colorectal
      cancer.
AB  - PURPOSE: The primary aim was to respectively evaluate PLA2G4A mutants modifying
      protective effect of tea consumption against colorectal cancer (CRC), colon and
      rectal cancer. METHODS: All participants were recruited from January 2006 to
      April 2008. The information about tea consumption was collected by a structured
      questionnaire. CRC patients were diagnosed based on histology. Four single
      nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic
      regression models were used for assessing the joint effects between tea
      consumption and SNPs on CRC, colon and rectal cancer. RESULTS: Three hundred
      patients with CRC and 296 controls well-matched were used in the final analyses.
      The significant individual associations between four SNPs (rs6666834, rs10911933,
      rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype
      was significantly associated with the increased risk of CRC (OR = 3.06; 95%CI =
      1.52-6.19), compared with TCAC haplotype. Drinking tea was correlated with a
      decreased risk of CRC after adjustment for covariates (OR = 0.61; 95%CI = 0.39
      0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834,
      tea drinkers with TT/CT or CC had significant lower risk of CRC (OR = 0.6, 95%CI
      = 0.36-1.00 for TT/CT; 0.38, 0.19-0.74 for CC). The joint effects between the
      remaining three SNPs and drinking tea on CRC were observed as well. Similar
      findings were observed on colon and rectal cancers. CONCLUSIONS: Tea consumption
      and haplotype of mutants in PLA2G4A gene were respectively associated with the
      risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption
      against CRC, colon and rectal cancers in Chinese population.

PMID- 22358384
TI  - Bilateral laparoscopic adrenalectomy for synchronous metastasis of colonic
      cancer.

PMID- 22358385
TI  - Resectability and outcome with anti-EGFR agents in patients with KRAS wild-type
      colorectal liver-limited metastases: a meta-analysis.
AB  - BACKGROUND: Cetuximab (C) and panitumumab (P) increase response rate and survival
      in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta
      analysis of randomised controlled trials (RCTs) to assess their effect on overall
      response rate (ORR), the rate of radical resection (R0) and survival in patients
      with liver-limited initially unresectable mCRC. MATERIALS AND METHODS: We
      searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials
      for RCTs comparing first-line chemotherapy plus or minus C or P and reporting
      data in patients with KRAS wild-type, unresectable liver-limited mCRC. Relative
      risks (RRs) with 95% confidence interval were calculated. Meta-analysis of hazard
      ratios (HRs) for progression-free and overall survival (PFS and OS) was also
      performed. RESULTS: Four RCTs involving 484 KRAS wild-type patients were
      included. Compared to chemotherapy alone, the addition of C or P significantly
      increased the ORR (RR 1.67, p = 0.0001), the R0 resection rate from 11% to 18%
      (RR 1.59, p = 0.04) and PFS (HR 0.68, p = 0.002), but not OS (p = 0.42).
      CONCLUSIONS: The addition of C and P increased the R0 resection rate by 60% and
      reduced the risk of progression by 32% in patients with mCRC and unresectable
      liver-limited disease. This combination represents one of the preferred choices
      as conversion therapy in KRAS wild-type patients with unresectable liver
      metastases.

PMID- 22358386
TI  - Spectral characteristics, DNA-binding and cytotoxicity of two functional Ru(II)
      mixed-ligand complexes.
AB  - Two functional Ru(II) mixed-ligand complexes, [Ru(phen)(2)(ttbd)](2+) (1) (ttbd =
      4-(6-propenyl-pyrido[3,2-a]phenzain-10-yl-benzene-1,2-diamine, phen = 1,10
      phenanthroline) and [Ru(bpy)(2)(ttbd)](2+) (2) (bpy = 2,2'-bipyridine), have been
      synthesized and characterized. The spectral characteristics of complexes 1 and 2
      were investigated using fluorescence spectroscopy and revealed that both
      complexes were very sensitive to solvent polarity and oxygen molecules in
      nonaqueous solvents. The binding properties of the two complexes towards calf
      thymus DNA (CT-DNA) were investigated with different spectrophotometric methods,
      viscosity measurements and quantum chemistry calculations, indicating that both
      complexes could enantioselectively bind to CT-DNA by means of intercalation, but
      with different binding strengths and discrimination. On the other hand, the
      cytotoxicity of both complexes have been evaluated by MTT assays and Giemsa
      staining experiments. The main results reveal that the hydrophobicity and surface
      area of the ancillary ligands have a significant effect on their DNA binding
      behavior and both complexes are likely to be useful for optically probing
      nonaqueous and oxygen-free environments.

PMID- 22358387
TI  - White paper on radiation protection by the European Society of Radiology.
AB  - In the past decade, the medical effective dose per caput has increased in most
      European countries because of CT; it now ranges between 0.4 and 2 mSv/year. The
      biological impact of diagnostic imaging exposure is dominated by stochastic
      effects: based on the linear-no-threshold hypothesis, the risk of cancer
      induction is estimated to increase proportionally to organ dose, reaching around
      0.5% at an effective dose of 100 mSv. The risk is higher the younger the age at
      the time of exposure, it is different for different organs, and women are more
      susceptible than men. Fluoroscopy-based imaging, above all intervention, may
      reach the dose threshold for deterministic effects, observed most often at the
      skin above around 3 Gy, and it is also the major source of occupational exposure
      in radiology. This white paper discusses the role of justification, evidence
      based referral guidelines, optimization, diagnostic reference levels, clinical
      audits and quality assurance programs. The ESR strongly supports education and
      training of the medical staff involved in imaging by ionizing radiation. It
      disseminates information regarding radiation protection, takes initiatives,
      cooperates with partners and supports projects in justification as well as
      optimization. To reach these aims, the ESR cooperates with other organizations
      involved in radiation protection.

PMID- 22358388
TI  - The hydrogen evolution reaction in a room temperature ionic liquid: mechanism and
      electrocatalyst trends.
AB  - The kinetics and mechanism of the proton reduction reaction in the room
      temperature ionic liquid 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([C(2)mim][NTf(2)]) was studied at gold,
      molybdenum, nickel, titanium and platinum electrodes. Significant differences in
      electrochemical rate constants were observed between the different metals and
      with the corresponding processes in aqueous solution. The hydrogen evolution
      mechanism was consistent at all five metals in the ionic liquid, in stark
      contrast to the known behaviour in aqueous systems.

PMID- 22358389
TI  - Assembly and disassembly of a Zn10 high-nuclearity circular helicate.
AB  - A nano-scale decanuclear Zn(II) circular helicate is synthesized without the aid
      of counteranions during the assembly process, and can be totally disassembled
      into its reactants by specific anions.

PMID- 22358390
TI  - The role of betaIII-tubulin in non-small cell lung cancer patients treated by
      taxane-based chemotherapy.
AB  - BACKGROUND: The aim of this study is to evaluate whether class III beta-tubulin
      (TUBB3) expression could predict progression-free survival or overall survival in
      relapsed non-small cell lung cancer (NSCLC) patients treated with taxene-based
      chemotherapy. METHODS: Immunohistochemistal staining was used to examine the
      expression of TUBB3 in resected lung tumor specimens obtained from 56 patients
      treated with platinum-based chemotherapy against recurrent tumors after curative
      resections. Excision repair cross-complementation group 1, breast cancer
      susceptibility gene 1, vascular endothelial growth factor, Ki-67, CD34, and p53
      were also correlated with clinical features and outcome after treatment. RESULTS:
      Of the 56 patients enrolled in the study, 29 were treated by carboplatin plus
      paclitaxel as first-line treatment, and 24 patients received docetaxel
      monotherapy as second- or third-line treatment. A positive TUBB3 expression is
      closely associated with a poor response to taxane-based chemotherapy. TUBB3
      expression was an independent prognostic factor for predicting poor progression
      free survival after docetaxel administration. However, TUBB3 expression could not
      predict outcome after carboplatin plus paclitaxel treatment. The other biomarkers
      tested were not independent prognostic factors for predicting outcome after
      taxane-based chemotherapy. CONCLUSION: TUBB3 expression is associated with
      resistance to taxane-based chemotherapy and is an independent prognostic factor
      for predicting poor progression-free survival after docetaxel treatment alone.
      TUBB3 expression may be a predictive marker for chemoresistance to docetaxel in
      NSCLC with postoperative recurrent disease.

PMID- 22358391
TI  - Porphyrin and phthalocyanine glycodendritic conjugates: synthesis, photophysical
      and photochemical properties.
AB  - Synthesis of water soluble porphyrin and phthalocyanine derivatives with,
      respectively, eight and sixteen galactose units has been carried out. The
      combined preliminary photophysical and photochemical features of the new products
      suggest that they might be promising photodynamic therapeutic agents.

PMID- 22358392
TI  - Theoretical study of two-photon absorption properties and up-conversion
      efficiency of new symmetric organic pi-conjugated molecules for photovoltaic
      devices.
AB  - Organic material with high intensity of two-photon absorption (TPA) induced
      fluorescence can be used as the frequency up-converter materials for improving
      efficiency of the solar cells. In this work, the organic molecular structures
      were designed by symmetrically grafting two elongated conjugated linkers on a
      conjugated core and then adding donor groups at both terminals. Fluorene
      derivatives as a core acceptor, phenylethynyl as the conjugated linker and
      diphenylamino or methyl-9H-carbozole as the donor end groups were selected.
      Quantum mechanical modeling techniques were applied to investigate the molecular
      electronic structure and properties. Absorption properties of these novel pi
      conjugated organic molecules were studied. The TPA cross-sections of these
      derivatives were calculated using few-states models, respectively. The effects of
      donor and acceptor groups on the TPA behaviors of these designed molecules were
      investigated. The up-conversion efficiency of designed molecules was also
      calculated.

PMID- 22358393
TI  - Antimicrobial resistance: a risk factor for infectious diseases.

PMID- 22358394
TI  - Communication of evidence-the first step toward antimicrobial resistance
      containment.

PMID- 22358395
TI  - Antimicrobial resistance in the age of noncommunicable diseases.

PMID- 22358396
TI  - [Antibacterial drug resistance in Latin America: consequences for infectious
      disease control].
AB  - Antibacterial drug resistance is a particularly significant issue in Latin
      America. This article explores antimicrobial resistance in three classes of
      clinically important bacteria: gram-positive bacteria, enterobacteria, and
      nonfermenting gram-negative bacilli. The gram-positive bacteria frequently
      responsible for infections in humans are for the most part cocci: staphylococci,
      streptococci (including pneumococci), and enterococci, in both community and
      hospital settings. This situation is no different in the Region of the Americas.
      Among the gram-positive bacteria, the causative agents of bacteremia are most
      commonly strains of coagulase-negative Staphylococcus, followed by enterococci.
      This report explores the resistance of these species to different antimicrobial
      drugs, resistance mechanisms in community and hospital strains, and new drugs for
      treating infections caused by these bacteria. In Latin America, antimicrobial
      resistance in Enterococcus strains is still a minor problem compared to the
      situation in the United States. The strains of the genus Streptococcus isolated
      from respiratory infections are still sensitive to penicillin. Furthermore, the
      resistance of enterobacteria is extremely important in the Region, particularly
      because of the broad dissemination of CTX-M extended-spectrum beta-lactamases
      (ESBL), some of which originated in Latin America. This article analyzes the
      resistance of Streptococcus pneumoniae, beta-hemolytic streptococci, and viridans
      group streptococci. Among the nonfermenting gram-negative bacilli, while
      Pseudomonas aeruginosa strains remain the leading cause of bacteremia, infections
      caused by strains of Acinetobacter spp. have proliferated extensively in some
      areas. With regard to antibiotics, several options are available for treating
      gram-positive bacterial infections. The same cannot be said for infections caused
      by enterobacteria and nonfermenting gram-negative bacilli, where options for the
      effective treatment of patients are still insufficient.

PMID- 22358397
TI  - [Frequency of enzymes associated with reduced sensitivity to beta-lactam
      antibiotics in enterobacteria isolates, Caracas, Venezuela].
AB  - OBJECTIVE: To determine the frequency of enzymatic mechanisms associated with
      reduced sensitivity to broad-spectrum beta-lactam antibiotics in enterobacteria
      isolates obtained at hospital centers in Caracas, Venezuela. METHODS: A cross
      sectional study was conducted on enterobacteria isolated from patients at eight
      hospital centers in Caracas, Venezuela, from 15 October 2009 to 15 January 2010.
      The species were identified using conventional biochemical tests, and their
      susceptibility to antimicrobial drugs was assessed by antibiogram (Kirby-Bauer
      method), using the 2010 performance standards published by the Clinical and
      Laboratory Standards Institute. Beta-lactam-resistant genes were detected using
      an enhanced polymerase chain reaction assay. RESULTS: Of 1 235 isolates, 207
      (16.8%) exhibited resistance to third- and fourth-generation cephalosporins,
      carbapenems, or both. They presented the following phenotypes: extended-spectrum
      beta-lactamase (ESBL), 93.8%; depressed AmpC, 4.3%; and carbapenemase, 1.9%.
      Further characterization of the first two phenotypes yielded the following
      breakdown of types: SHV, 36.7%; CTX-M-1 group, 22.3%; TEM, 21.7%; CTX-M-1 group
      with impermeability, 5.2%; two-enzyme combinations, 4.5%; CTX-M-2 group, 4.3%;
      PER, 3.4%; and KPC, 1.9%. The SHV type was predominant in the public hospital
      strains, whereas the CTX-M-1 group was most common in the strains from the
      private hospitals. CONCLUSIONS: Of the enzymatic mechanisms investigated, the SHV
      type was the most frequent, followed by the CTX-M-1 group and the TEM type. Also,
      a high percentage of type KPC was found. The research reported here is one of
      only a few multicenter studies that have been conducted in Venezuela to evaluate
      the frequency of this type of antimicrobial resistance mechanism, including
      phenotypical and molecular characterization. It was shown that the detection
      methods require proper interpretation of sensitivity profiles and molecular
      confirmation of the mechanism present.

PMID- 22358398
TI  - Methicillin-resistant Staphylococcus aureus DNA electrophoretic pattern: temporal
      changes in an endemic hospital environment.
AB  - OBJECTIVE: To describe the analysis of geographical and temporal distribution of
      DNA profiles determined by pulsed-field gel electrophoresis (PFGE) of methicillin
      resistant Staphylococcus aureus (MRSA) strains isolated from hospitalized
      patients in a tertiary care university hospital in Brazil. METHODS: Ninetynine
      samples of MRSA obtained from 89 patients in the period 1999-2004 were studied.
      MRSA strains were isolated from central venous catheters (33 isolates) and
      bloodstream infections (66 strains). PFGE with 20 units of SmaI restriction
      endonuclease was used for genomic typing. RESULTS: Analysis of DNA PFGE of 99
      strains of MRSA revealed 26 profiles and their respective related profiles. The
      mean time interval for detecting MRSA infection was 26 days from hospital
      admission. Forty-nine patients (57.6%) had a recent hospitalization. The DNA PFGE
      MRSA profiles were distributed in three clonal groups-I, II, and III-according to
      the period of time when the MRSA strains were isolated. DNA PFGE MRSA profiles
      were spread homogeneously through all hospital wards. CONCLUSIONS: Changes in the
      distribution of DNA PFGE MRSA profiles were largely temporal, with clonal groups
      being replaced over time, without predominance in any hospital ward or any
      specific area of the hospital.

PMID- 22358399
TI  - [Detection of rifampicin-resistant strains of Neisseria meningitidis in Uruguay].
AB  - The objective of this study was to characterize the phenotype and genotype of two
      isolates of rifampicin-resistant Neisseria meningitidis associated with two
      independent events involving transmission of severe meningococcal meningitis that
      occurred in September and October 2010 in Montevideo, Uruguay. The most recent 10
      years of data from the national antimicrobial resistance surveillance system were
      reviewed to estimate the frequency of the particular meningococcal features that
      were characterized. Rifampicin resistance was studied using the epsilometer test.
      The serotype and serosubtype of the isolates were determined by ELISA, and the
      genotype was characterized using DNA digestion with Nhel and pulse field gel
      electrophoresis. The two isolates were identical: B:2a:P1.5. In the collection of
      408 strains of N. meningitidis isolated in Uruguay in the past 10 years, the
      phenotype only appeared in two isolates, which were sensitive to rifampicin. The
      two isolates studied also shared a single pulse type, which was different from
      that of two other rifampicin-resistant isolates obtained in 2003 and 2007.
      Consequently, it was concluded that both cases of transmission were caused by a
      single rifampicin-resistant strain, which could have been an import from another
      country or else the result of a drift from serogroup C to B due to selective
      pressure exerted by vaccines administered to the population. It is essential to
      maintain and maximize surveillance. However, since this type of finding has been
      sporadic so far, unless a secondary case is identified, there is no justification
      for changing the antimicrobial drug currently being administered to contacts as
      prophylaxis.

PMID- 22358400
TI  - [Carbapenem resistance in Pseudomonas aeruginosa isolates: an example of
      interaction between different mechanisms].
AB  - OBJECTIVE: To identify the outer membrane protein absent in the resistant
      isolates and to determine both the causes of its absence in the membrane and the
      presence of other mechanisms of carbapenem resistance in clinical isolates of
      Pseudomonas aeruginosa. METHODS: Twenty isolates from an outbreak of P.
      aeruginosa previously characterized as metallo-beta-lactamase IMP-13 producers
      were studied. All the isolates exhibited equal expression of the IMP-13 enzyme,
      but only five of them were carbapenem-resistant. It was found that the five
      resistant isolates lacked a outer membrane protein. The oprD and ampC genes were
      sequenced; the outer membrane proteins were identified using matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry; the
      OprD and AmpC expressions, as well as the Mex efflux system, were assessed by
      real-time polymerase chain reaction; and finally, the contribution of reduced
      OprD to carbapenem resistance was determined. RESULTS: The absent outer membrane
      protein in group R was identified as OprD-TS; however, no variations in its
      expression were observed. The oprD gene presented mutations in the five resistant
      isolates. The production of AmpC PDC-5-type enzyme and the MexAB-OprM efflux
      system was the same in both carbapenem-sensitive and -resistant isolates. The
      contribution of the combined presence of IMP-13 and reduced OprD to increased
      resistance was examined. CONCLUSIONS: Different mechanisms contribute to
      carbapenem resistance in IMP-13-producing isolates. The possibility that these
      IMP-13-producing isolates could go undetected poses a latent risk when selecting
      mutants with added resistance mechanisms in order to enhance carbapenem
      resistance.

PMID- 22358401
TI  - [Antimicrobial susceptibility and genetic bases for resistance of infection
      causing Enterococcus strains in Cuba].
AB  - OBJECTIVE: To identify infection-causing Enterococcus species in Cuban hospitals
      and determine their susceptibility to antimicrobial drugs, as well as their
      resistance mechanisms. METHODS: A total of 687 Enterococcus isolates from 30
      Cuban hospitals in nine provinces of the country were studied over the period
      2000-2009. The species were identified using both the conventional method and the
      automatic API((r)) system. The minimum inhibitory concentration was determined
      for 13 antimicrobial drugs following the standards recommended by the Clinical
      Laboratory and Standards Institute. The polymerase chain reaction technique was
      used to characterize the genes that were resistant to aminoglycosides,
      erythromycin, tetracycline, and glucopeptides. The presence of beta-lactamase was
      determined by the chromogenic cephalosporin test. RESULTS: The most prevalent
      species were Enterococcus faecalis (82.9%) and E. faecium (12.2%). Resistance to
      glucopeptides (1.0%) was mediated by the vanA and vanB genes. The strains
      resistant to ampicillin (6%) did not produce beta-lactamases. A high percentage
      of resistance to aminoglycosides was observed. Gentamicin (31.0%) and
      streptomycin and amikacin (29.1%) were mediated by the aac(6')Ie-aph(2")Ia,
      aph(3')-IIIa, ant(6)Ia, and ant(3")(9) genes. A correlation was found between
      resistance to tetracycline (56.0%) and presence of the tet(M) (75.1%) and tet(L)
      genes (7.0%), while resistance to erythromycin (34.1%) was due to the erm(B) gene
      (70.9%). CONCLUSIONS: Resistance to vancomycin is infrequent in Cuba, as opposed
      to a high level of resistance to aminoglycosides, which may be indicative of
      treatment failures. The microbiology laboratory is a cornerstone of Enterococcus
      infection surveillance, along with ongoing monitoring of the susceptibility of
      these infections to antimicrobial drugs at a time when resistance of this
      microorganism is on the rise.

PMID- 22358402
TI  - Prevalence and antimicrobial resistance of Salmonella in chicken carcasses at
      retail in 15 Brazilian cities.
AB  - OBJECTIVE: To describe the prevalence and antimicrobial resistance of Salmonella
      spp. in frozen chicken carcasses at retail from 15 Brazilian cities. METHODS: A
      descriptive study of data from the Brazilian National Program for Monitoring the
      Prevalence of Bacterial Resistance in Chicken (PREBAF) was conducted from
      September 2004 to July 2006. The program collected chicken carcasses in 15 state
      capitals of Brazil in the five geographic regions of the country. Standardized
      methodologies were used to isolate Salmonella-spp. and identify serotypes. The
      minimal inhibitory concentration method was used to test resistance to 18
      antimicrobials. RESULTS: In 2 679 carcasses examined, the prevalence of
      Salmonella spp. was 2.7% (range 0.0%-8.9%). Sao Paulo State produced 50.6% of
      positive samples. Eighteen serotypes were identified. The most frequently
      occurring were Salmonella Enteritidis (48.8%), Salmonella Infantis (7.6%),
      Salmonella Typhimurium (7.2%), and Salmonella Heidelberg (6.4%). All 250 strains
      tested were resistant to one or more antibiotics, and 133 (53.2%) were multidrug
      resistant (>= 3 classes). S. Heidelberg was resistant to ceftriaxone (75.0%) and
      to ceftiofur(43.8%). CONCLUSIONS: The prevalence of Salmonella spp. found in this
      study was relatively low. However, there were a high proportion of multidrug
      resistant strains, including third-generation cephalosporins used to treat
      invasive salmonellosis. The results confirm the relevance of the PREBAF program.
      It is recommended that PREBAF be improved, including a timely data analysis. A
      review of permitted limits for Salmonella spp. in retail chicken in Brazil is
      also needed.

PMID- 22358403
TI  - [Serotypes and antimicrobial susceptibility patterns of Salmonella strains
      isolated from food in Cuba].
AB  - The serotypes of 178 isolates of Salmonella enterica taken from food in different
      regions of Cuba between January 2008 and December 2009 were identified, and the
      antimicrobial susceptibility pattern of 100 selected isolates was determined by
      strata sampling. A total of 20 Salmonella serotypes were identified, with a
      predominance of S. Enteritidis (23%), S. Agona (13.5%), and S. London (11.2%). Of
      all the strains, 75% were resistant or presented intermediate resistance to at
      least one of the drugs tested, in the following order: tetracycline (70.7%),
      ampicillin (22.7%), and nalidixic acid (14.7%). Ten different resistance patterns
      were identified. The most frequent patterns corresponded to strains that were
      either drug-resistant or had intermediate resistance (89.3%). Three strains
      (identified as S. Infantis, S. Derby, and S. Enteritidis) were multiresistant,
      and one of them, S. Enteritidis, was not sensitive to either nalidixic acid or
      ciprofloxacin. To control salmonellosis, the importance of maximizing integrated
      health surveillance is emphasized.

PMID- 22358404
TI  - Ecosystem approach to promoting appropriate antibiotic use for children in
      indigenous communities in Ecuador.
AB  - OBJECTIVE: To collect baseline data on infectious diseases and antibiotic use in
      two Andean indigenous communities in Ecuador in order to determine the
      feasibility and acceptability of applying an ecosystem approach to address
      associated problems. METHODS: In visits to 65 households with children under age
      5 years, environmental risk factors for infectious diseases were evaluated
      through rapid assessment. Caregivers' knowledge, attitudes, and practices related
      to antibiotic use were determined through a knowledge, practices, and coverage
      survey; antibiotic use was gleaned from inspection of medicine chests; and
      overall health of the 91 children (including nutritional status) was assessed. A
      workshop was held to share results and to craft a multicomponent intervention
      using an ecohealth framework. RESULTS: Numerous environmental risk factors were
      identified, especially related to water and sanitation. Knowledge, attitudes, and
      practices revealed use of traditional and Western medicines and serious knowledge
      gaps. Antibiotics were present in 60.9% of households in Correuco and 46.8% in La
      Posta; malnutrition rates were 22.2% in Correuco and 26.1% in La Posta; diarrheic
      episodes were experienced in the previous month by 26.7% of children in Correuco
      and 47.8% in La Posta, with antibiotics prescribed in 50.0% and 47.1% of cases,
      respectively; and acute respiratory infections were incurred by 28.9% of children
      in Correuco and 47.8% in La Posta, with antibiotics prescribed in 53.8% and 50.0%
      of cases, respectively. CONCLUSIONS: Environmental, social, and cultural factors
      must be addressed to prevent antibiotic resistance in addition to training health
      personnel. An ecosystem approach is well-suited for this goal.

PMID- 22358405
TI  - Physicians' responsibility for antibiotic use in infants from periurban Lima,
      Peru.
AB  - OBJECTIVE: To describe the use of antibiotics in Peruvian children under 1 year
      in a setting where they are available without a prescription. METHODS: Data were
      analyzed from a cohort study between September 2006 and December 2007 of 1 023
      children < 2 months old in periurban Lima, Peru, followed until they were 1 year
      old. RESULTS: Seven hundred seventy of 1 023 (75.3%) children took 2 085 courses
      of antibiotics. There were two courses per child per year (range 0-12). Higher
      rates of antibiotic use were found in children 3-6 months old (37.2%).
      Antibiotics were given to children for 8.2% of common colds, 58.6% of all
      pharyngitis, 66.0% of bronchitis, 40.7% of diarrheas, 22.8% of dermatitis, and
      12.0% of bronchial obstructions. A physician's prescription was the most common
      reason for antibiotic use (90.8%). Medication use without a prescription was
      found in 6.9% of children, and in 63.9% of them it was preceded by a physician's
      prescription. CONCLUSIONS: Infants are often exposed to antibiotics in this
      setting. Overuse of antibiotics is common for diagnoses such as pharyngitis,
      bronchitis, bronchial obstruction, and diarrhea but is typically inappropriate
      (83.1% of courses) based on the most common etiologies for this age group.
      Interventions to improve the use of antibiotics should focus on physicians, since
      a physician's prescription was the most common reason for antibiotic use.

PMID- 22358406
TI  - [Reasons for inappropriate prescribing of antibiotics in a high-complexity
      pediatric hospital].
AB  - OBJECTIVE: Determine the reasons for inappropriate prescription of antibiotics
      and identify opportunities to improve prescription of these drugs in pediatric
      patients hospitalized in intermediate and intensive care units. METHODS: A
      prospective, descriptive longitudinal study was conducted of pediatric patients
      in intermediate and intensive care units who received parenteral administration
      of antibiotics, with the exception of newborns, burn unit patients, and surgical
      prophylaxis patients. A univariate analysis and multiple logistic regression were
      performed. RESULTS: A total of 376 patients with a median of age of 50 months
      were studied (interquartile range [IQR] 14.5-127 months). Out of the total
      patients studied, 75% had one or more underlying conditions. A total of 40.6% of
      these patients had an oncologic pathology and 33.5% had neurological conditions.
      The remaining 25.9% had other underlying conditions. Antibiotic treatment was
      inappropriate in 35.6% of the patients studied (N = 134). In 73 (54.4%) of the
      134 cases, inappropriate use was due to the type of antibiotic prescribed, the
      dose administered, or the treatment period. The 61 (45.5%) remaining cases did
      not require antibiotic treatment. In the multivariate analysis, the risk factors
      for inappropriate use of antibiotics were: administration of ceftriaxone OR 2
      (95% CI, 1.3-3.7; P = 0.02); acute lower respiratory tract infection OR 1.8 (95%
      CI, 1.1-3.3; P < 0.04); onset of fever of unknown origin in hospital inpatients
      OR 5.55 (95% CI, 2.5-12; P < 0.0001); and febrile neutropenia OR 0.3 (95% CI, 0.1
      0.7; P = 0.009). CONCLUSIONS: Inappropriate use of antibiotics was less common in
      the clinical conditions that were well-characterized. Prescribing practices that
      could be improved were identified through the preparation and circulation of
      guidelines for antibiotic use in hospital inpatients.

PMID- 22358408
TI  - [Regulations governing the dispensing of medications and their effect on
      antibiotic consumption in Venezuela].
AB  - OBJECTIVE: Determine the variations in consumption trends for regulated and
      unregulated antibiotics in Venezuela in the period before (2005) and after (2006
      2008) the regulation of prescription sales was introduced. METHODS: Information
      on antibiotic consumption in Venezuela was obtained from the data provided by
      International Marketing Services. Consumption was expressed in daily doses per
      1,000 inhabitants. Analyses of variance (ANOVA) were performed, with a 95%
      confidence interval, to identify the differences between the periods studied.
      RESULTS: The regulated antibiotics with the highest consumption were
      ciprofloxacin and azithromycin. The classes of unregulated antibiotics with the
      highest consumption were penicillins and first-generation cephalosporins,
      aminoglycosides, diaminopyridine-sulfonamides, and tetracyclines. Total
      consumption in the categories of antibiotics with unregulated dispensing was
      twice as high as in the categories with regulated sales, both before and after
      introduction of the regulation. CONCLUSIONS: There were no statistically
      significant differences in antibiotic consumption with regulated or unregulated
      dispensing, either before or after the introduction of measures regulating the
      dispensing of antibiotics.

PMID- 22358407
TI  - [Restriction of antibiotic sales in pharmacies in Bogota, Colombia: a descriptive
      study].
AB  - OBJECTIVE: Describe the implementation status of a regulation prohibiting
      antibiotic sales without a medical prescription in pharmacies of Bogota,
      Colombia. METHODS: A cross-sectional descriptive study was conducted using the
      simulated purchase technique in Bogota pharmacies (drugstores). The sample of 263
      pharmacies was calculated by stratification (chain pharmacies and independent
      pharmacies) with 5% accuracy and a 2% correction factor. Simple randomization was
      assigned in each stratum. RESULTS: Out of the total pharmacies studied, 80.3% did
      not comply with the regulation established for prescription sales of antibiotics.
      In 20.1% of the cases, the dispenser asked about the patient's age, symptoms, or
      both age and symptoms in order to offer other drugs or change the antibiotic.
      There were no inquiries about a medical history of allergy to antibiotics. In
      cases in which there was the intention to sell antibiotics, the generic format
      was most commonly offered (81.2%). Some drug dispensers made inappropriate
      recommendations. The locations with the highest levels of noncompliance with the
      regulation were also those with high rates of unmet basic needs. CONCLUSIONS:
      Five years after passage of a regulation to halt the unrestricted sales of
      antibiotics, there is minimal compliance, and dispensing does not conform to the
      established parameters. Pharmacy personnel do not provide the required
      information according to their responsibilities.

PMID- 22358409
TI  - [Impact of a quality control program on antibiotic prescription in a hospital in
      Havana, Cuba].
AB  - OBJECTIVE: Demonstrate the efficacy of a quality control program on antibiotic
      prescription in Joaquin Albarran Hospital in Havana, Cuba. METHODS: An
      interventional study was conducted from 1 May 2008 to 31 March 2011. The study
      included evaluation of prescription quality, information feedback, educational
      activities, the operations of an antibiotic committee, and the preparation of
      protocols on antimicrobial drug use. A simple arithmetic graph of the time series
      was constructed, and the absolute values of the series percentages were compared.
      In order to verify the existence of a series trend, a simple linear regression
      model was applied. RESULTS: Antibiotic prescription was evaluated in 2 941
      patients. An irregular series was observed, with inappropriate use in 30.7%-48.4%
      of these patients in the first three months analyzed. The value of the regression
      slope was close to zero, although it was negative and significantly different
      from zero (beta = -0.29; P = 0.02). CONCLUSIONS: The antibiotic control program
      improved the quality of prescribing for hospital patients.

PMID- 22358410
TI  - Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less
      incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas
      aeruginosa.
AB  - OBJECTIVE: To determine whether restricting the use of ceftriaxone and
      ciprofloxacin could significantly reduce colonization and infection with
      resistant Gram-negative bacilli (r-GNB). METHODS: A two-phase prospective study
      (before/after design) was conducted in an intensive care unit in two time periods
      (2004-2006). During phase 1, there was no antibiotic restriction. During phase 2,
      use of ceftriaxone or ciprofloxacin was restricted. RESULTS: Atotal of 200
      patients were prospectively evaluated. In phase 2, the use of ceftriaxone was
      reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041),
      accompanied by a 113.8% increase in use of ampicillin-sulbactam (P =
      0.002).During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB
      (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non
      r-GNB (57.8%)](P = 0.0002). Acinetobacter spp. was isolated 13 times during phase
      1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas
      aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2
      (P = 0.0108). CONCLUSIONS: Restriction of ceftriaxone and ciprofloxacin reduced
      colonization by Acinetobacter spp. and improved the susceptibility profile of P.
      aeruginosa.

PMID- 22358411
TI  - [Frequency of nasal carriers of methicillin-resistant Staphylococcus aureus among
      health workers in Nicaraguan hospitals].
AB  - OBJECTIVE: To determine the frequency of nasal carriers of strains of methicillin
      resistant Staphylococcus aureus (MRSA) and the antimicrobial resistance pattern
      of these strains, obtained from health workers from four hospitals in Nicaragua.
      METHODS: A descriptive cross-sectional study was conducted between 1 June 2009
      and 30 September 2010. Nasal swabs were taken from health workers who voluntarily
      agreed to participate in the study, and were cultured on an oxacillin-resistant
      screening agar base (ORSAB) medium. The S. aureus isolates were identified using
      ordinary methods, and methicillin resistance was confirmed based on the presence
      of the mecA gene using the polymerase chain reaction technique. The antimicrobial
      resistance pattern was detected by the disk diffusion method. Each participant
      signed an informed consent form before the samples were taken. RESULTS: A total
      of 569 health workers participated in the study: 208 from one hospital in Leon,
      155 from two hospitals in Chinandega, and 206 from one hospital in Managua. The
      frequency of nasal MRSA carriers was 9.6% in Leon, 11.6% in Chinandega, and 6.7%
      in Managua. The MRSA resistance profile was similar in the four hospitals, and
      all the strains were sensitive to vancomycin. Of the total MRSA strains isolated,
      15% were multi-drug resistant. Erythromycin had the highest percentage of
      resistance, followed by clindamycin. CONCLUSIONS: The results of the study may be
      regarded as a warning that MRSA strains are circulating among health workers in
      the participating hospitals. The study also contributes important information
      regarding the resistance profile of MRSA strains.

PMID- 22358412
TI  - [Surveillance of resistance to antitubercular drugs in Cuba, 2000-2009].
AB  - OBJECTIVE: Determine the prevalence of resistance to antitubercular drugs in Cuba
      in the 2000-2009 decade. METHODS: A prospective longitudinal study was conducted.
      The sample group consisted of 2,285 Mycobacterium tuberculosis isolates obtained
      from throughout the country in the period from 1 January 2000 to 31 December
      2009. The proportion method was used in Lowenstein-Jensen media with the first
      line drugs: isoniazid, streptomycin, ethambutol, and rifampicin. RESULTS: In the
      new cases and patients with a history of previous treatment, resistance was 8.5%
      and 37.0%, respectively. In these case categories, multidrug resistance was 0.4%
      and 8.8%, respectively. CONCLUSIONS: This study shows low prevalence of multidrug
      resistant strains in Cuba. The results reflect the progress made by the national
      control program, which is currently working on the elimination of tuberculosis as
      a public health problem in the country.

PMID- 22358414
TI  - [Trends of bacterial resistance phenotypes in high-complexity public and private
      hospitals in Colombia].
AB  - OBJECTIVE: Describe and compare the frequency of bacterial resistance phenotypes
      of microorganisms obtained from patients in intensive care units (ICU) and other
      (non-ICU) high-complexity public and private hospital services in Colombia.
      METHODS: A retrospective observational, analytical, multicenter study was
      conducted. The records from January 2007 to December 2009 on bacterial isolates
      and bacterial resistance phenotypes of microorganisms obtained from ICU and non
      ICU patients in 79 high-complexity public and private hospitals were
      consolidated. The information was analyzed with the WHONET((r)) 5.5 (WHO)
      software, following the 2009 recommendations of the Clinical and Laboratory
      Standards Institute, and summarized on an Excel((r)) spreadsheet. A descriptive
      analysis with the calculation of proportions was performed. The trends were
      analyzed with Spearman rank correlation. RESULTS: The 2007-2009 trends for
      bacterial resistance phenotypes show increased percentages of vancomycin
      resistant Enterococcus faecium, imipenem-resistant Klebsiella pneumoniae,
      ciprofloxacin-resistant K. pneumoniae, ceftazidime-resistant Escherichia coli and
      cefotaxime-resistant Enterobacter cloacae (r = 1, P < 0.01), and reduced
      percentages of ciprofloxacin-resistant E. coli, ceftazidime-resistant K.
      pneumoniae, oxacillin-resistant Staphylococcus aureus, ceftazidime-resistant
      Pseudomonas aeruginosa, and ciprofloxacin-resistant P. aeruginosa (r = -1, P <
      0.01). CONCLUSIONS: The trend analysis presented in this study is the baseline
      for establishing a national epidemiological surveillance subsystem. The trends
      observed reveal that bacterial resistance to antimicrobial drugs in hospitals in
      Colombia is a dynamic phenomenon, with evidence of the emergence of vancomycin
      resistant E. faecium and imipenem-resistant K. pneumoniae phenotypes in the
      hospitals.

PMID- 22358413
TI  - [Capability of national reference laboratories in Latin America to detect
      emerging resistance mechanisms].
AB  - OBJECTIVE: To evaluate the capability of 17 national reference laboratories
      participating in the Latin American Quality Control Program in Bacteriology and
      Antibiotic Resistance (LA-EQAS) to detect emerging resistance mechanisms- namely:
      resistance of enterobacteria to carbapenems due to the presence of Klebsiella
      pneumoniae carbapenemase (KPC) and metallo-beta-lactamase (MBL) type IMP, and
      intermediate resistance of Staphylococcus aureus isolates to vancomycin
      (vancomycin-intermediate resistant S. aureus-VISA). METHODS: The following three
      isolates were sent to the 17 participating LA-EQAS laboratories: KPC -producing
      Klebsiella pneumoniae PAHO-161, IMP-producing Enterobacter cloacae PAHO-166, and
      S. aureus PAHO-165 with intermediate resistance to vancomycin. Performance of
      each of the following operations was evaluated: interpretation of sensitivity
      tests, detection of the resistance mechanism, and assessment of either inhibition
      halo size (disk diffusion method) or minimum inhibitory concentration (MIC).
      RESULTS: Concordance in the detection of resistance mechanisms was 76.4%, 73.3%,
      and 66.7% for the K. pneumoniae PAHO-161, E. cloacae PAHO-166, and S. aureus PAHO
      165 strains, respectively. Concordance between the inhibition areas observed by
      the participating laboratories and the ranges established by the coordinating
      laboratory was acceptable for all three isolates, at 90.8%, 92.8%, and 88.9%,
      respectively. CONCLUSIONS: Overall concordance in on the detection of KPC, MBL,
      and VISA resistance mechanisms was 72.1%. We consider the national reference
      laboratories in Latin America capable of recognizing these emerging resistance
      mechanisms and expect that maximum levels of concordance will be reached in the
      future.

PMID- 22358415
TI  - Virological surveillance and antiviral resistance of human influenza virus in
      Argentina, 2005-2008.
AB  - OBJECTIVE: To describe the virological characteristics of the influenza strains
      circulating in Argentina in 2005-2008 and to assess the prevalence of antiviral
      resistance. METHODS: On the basis of their geographical spread and prevalence,
      influenza A and B isolates grown in Madin-Darby canine kidney cells were selected
      after antigenic and genomic characterization to be analyzed for antiviral
      resistance by enzymatic assay and pyrosequencing. Amantadine susceptibility was
      evaluated by pyrosequencing for known resistance markers on 45 strains of
      influenza A. Susceptibility to oseltamivir and zanamivir was evaluated by
      enzymatic assay of 67 influenza A and 46 influenza B strains, some of which were
      further analyzed by sequencing the neuraminidase gene. RESULTS: Resistance to
      amantadine was observed only on A(H3N2) strains (29/33); all of them carried the
      mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 12
      (34.3%) of the 35 A(H1N1) strains from 2008; all of them carried the mutation
      H275Y in their neuraminidase sequence. All these viruses remained sensitive to
      zanamivir. CONCLUSIONS: This study describes a high incidence of amantadine
      resistant influenza A(H3N2) viruses since 2006 and an unprecedented increase in
      oseltamivir resistance detected only in influenza A(H1N1) viruses isolated in
      2008. Influenza A and B viruses were more sensitive to oseltamivir than to
      zanamivir, and influenza A viruses were more sensitive to both neuraminidase
      inhibitors than the influenza B viruses. The national data generated and analyzed
      in this study may help increase knowledge about influenza antiviral drug
      resistance, which is a problem of global concern.

PMID- 22358416
TI  - Prevalence and patterns of HIV transmitted drug resistance in Guatemala.
AB  - OBJECTIVE: To assess human immunodeficiency virus (HIV) diversity and the
      prevalence of transmitted drug resistance (TDR) in Guatemala. METHODS: One
      hundred forty-five antiretroviral treatment-naive patients referred to the
      Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March
      2011. Plasma HIV pol sequences were obtained and TDR was assessed with the
      Stanford algorithm and the World Health Organization (WHO) TDR surveillance
      mutation list. RESULTS: HIV subtype B was highly prevalent in Guatemala (96.6%,
      140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145)
      prevalence of subtype C viruses were found. TDR prevalence for the study period
      was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO
      TDR surveillance mutation list. Most TDR cases were associated with non
      nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low
      prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors
      was observed in the cohort (< 1% for both families). Low selection of
      antiretroviral drug resistance mutations was found, except for NNRTI-associated
      mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher
      frequencies than expected in ART-naive populations. Higher literacy was
      associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). CONCLUSIONS:
      This study represents one of the first efforts to describe HIV diversity and TDR
      prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the
      intermediate level. Most TDR cases were associated with NNRTIs. Further and
      continuous TDR surveillance is necessary to gain more indepth knowledge about TDR
      spread and trends in Guatemala and to optimize treatment outcomes in the country.

PMID- 22358417
TI  - HIV transmitted drug resistance in adult and pediatric populations in Panama.
AB  - OBJECTIVE: To investigate the prevalence of transmitted drug-resistant HIV among
      adults in Panama by using a modified World Health Organization Threshold Survey
      (WHO-TS) and to investigate rates of initial resistance among HIV-positive
      infants in Panama. METHODS: At the Gorgas Memorial Institute, 47 HIV-positive
      adults were genotyped for mutations associated with transmitted drug resistance
      (TDR) in the reverse transcriptase and protease genes of HIV-1, according to WHO
      TS guidelines, modified to include patients <= 26 years old. Prevalence rates for
      drug-resistance mutations against three classes of antiretroviral drugs
      nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside
      reverse transcriptase inhibitors (NNRTIs), and protease inhibitors-were
      calculated as low (< 5.0%), moderate (5.0%-15.0%), and high (> 15.0%). Twenty
      five infant patients were also geno-typed and prevalence rates for drug
      resistance mutations were calculated. RESULTS: TDR among Panamanian adults was
      moderate: 6 of 47 HIV-positive adults showed one or more mutations associated
      with TDR. Horizontal TDR mutations were moderate for NRTIs and NNRTIs and low for
      protease inhibitors. Vertical transmission of HIV in Panama has decreased for
      2002-2007, but vertical HIV TDR prevalence is moderate (12.0%) and is emerging as
      a problem due to incomplete antiretroviral coverage in pregnancy. CONCLUSIONS:
      The prevalence of HIV TDR indicated by this study, combined with known rates of
      HIV infection in Panama, suggests more extensive surveys are needed to identify
      risk factors associated with transmission of HIV drug resistance. Specific WHO-TS
      guidelines for monitoring vertical transmission of drug-resistant HIV should be
      established.

PMID- 22358418
TI  - Progress of implementation of the World Health Organization strategy for HIV drug
      resistance control in Latin America and the Caribbean.
AB  - By the end of 2010, Latin America and the Caribbean (LAC) achieved 63%
      antiretroviral treatment (ART) coverage. Measures to control HIV drug resistance
      (HIVDR) at the country level are recommended to maximize the efficacy and
      sustainability of ART programs. Since 2006, the Pan American Health Organization
      has supported implementation of the World Health Organization (WHO) strategy for
      HIVDR prevention and assessment through regional capacity-building activities and
      direct technical cooperation in 30 LAC countries. By 2010, 85 sites in 19
      countries reported early warning indicators, providing information about the
      extent of potential drivers of drug resistance at the ART site. In 2009, 41.9% of
      sites did not achieve the WHO target of 100% appropriate first-line
      prescriptions; 6.3% still experienced high rates (> 20%) of loss to follow-up,
      and 16.2% had low retention of patients (< 70%) on first-line prescriptions in
      the first year of treatment. Stock-outs of antiretroviral drugs occurred at 22.7%
      of sites. Haiti, Guyana, and the Mesoamerican region are planning and
      implementing WHO HIVDR monitoring surveys or threshold surveys. New HIVDR
      surveillance tools for concentrated epidemics would promote further scale-up.
      Extending the WHO HIVDR lab network in Latin America is key to strengthening
      regional lab capacity to support quality assured HIVDR surveillance. The WHO
      HIVDR control strategy is feasible and can be rolled out in LAC. Integrating
      HIVDR activities in national HIV care and treatment plans is key to ensuring the
      sustainability of this strategy.

PMID- 22358419
TI  - The Canadian Institutes of Health Research Institute of Infection and Immunity
      response to the threat of antimicrobial resistance.

PMID- 22358420
TI  - [Comparative study of clones from isolates methicillin-resistant Staphylococcus
      aureus prevalent in Argentina].

PMID- 22358421
TI  - Antimicrobial stewardship program in a developing country: the epidemiological
      barrier.

PMID- 22358422
TI  - Adaptive behaviour in children and adolescents with foetal alcohol spectrum
      disorders: a comparison with specific learning disability and typical
      development.
AB  - Foetal alcohol spectrum disorders (FASD) is a leading cause of intellectual
      disability in the western world. Children and adolescents with FASD are often
      exposed to a double burden in life, as their neurological sequelae are
      accompanied by adverse living surroundings exposing them to further environmental
      risk. In the present study, the adaptive abilities of a group of children and
      adolescents with FASD were examined using the Vineland Adaptive Behaviour Scales
      (VABS) and compared to those of a group of IQ-matched children with specific
      learning disorder (SLD) as well as with typically developing controls (CON). The
      results showed significantly different adaptive abilities among the groups:
      Children with FASD performed worse than IQ-matched children with SLD, who in turn
      performed worse than typically developing children on all domains (communication,
      daily living skills and socialization) on the VABS. Compared to the other groups,
      social skills declined with age in the FASD group. These results support previous
      studies of adaptive behaviour deficits in children with FASD and provide further
      evidence of the specificity of these deficits. On a societal level, more efforts
      and resources should be focused on recognizing and diagnosing FASD and supporting
      communication skills, daily living skills and most of all social skills across
      diagnostic groups within FASD. Without adequate intervention, adolescents and
      young adults with FASD run a great risk of marginalization and social
      maladjustment, costly not only to society but also to the lives of the many young
      people with FASD.

PMID- 22358423
TI  - Deciphering the elusive nature of sharp bone trauma using epifluorescence
      macroscopy: a comparison study multiplexing classical imaging approaches.
AB  - Characterization of sharp-force trauma on human bones can be extremely useful in
      providing information regarding the nature and context of death. Nevertheless, in
      the identification of weapons used to cause sharp-force trauma and analysis of
      bone wounds, challenging tasks still remain. Current analysis attempting to
      dissect bone wound characteristics varied quite a lot and mixed different
      criteria, thus leading sometimes to conflicting results. In this context, the aim
      of our study is to clarify qualitative aspects of cut marks induced by sharp
      weapons on human bones. For that purpose, we analyzed bone samples via an
      original approach based on bone autofluorescence with an epifluorescence
      macroscope and compared it to previous existing methods. In this study, we used
      bone sections from human clavicles on which three different kinds of lesions were
      manually implemented, using different weapons. The bone wounds were analyzed by
      three different methodologies, light microscopy, scanning electron microscopy
      (SEM), and micro-computed tomography, and were compared with epifluorescence
      macroscopy. We paid attention more significantly to the aspect of walls and floor
      of the kerf, so as to conclude on the nature and distinguish between weapons
      used. Among all technologies used in this study, the most precise and efficient
      methods were epifluorescence macroscopy and SEM. Nonetheless, epifluorescence
      macroscopy is faster, cheaper, and more accessible than SEM. More significantly,
      this technique, which has the potential to accurately document the nature of the
      damage, is nondestructive, and could thus be highly useful in forensic science as
      anthropology.

PMID- 22358424
TI  - Anxiolytic effects of repeated treatment with an essential oil from Lippia alba
      and (R)-(-)-carvone in the elevated T-maze.
AB  - Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions
      of Central and South America as a tranquilizer. The plant's anxiolytic
      properties, however, merit investigation. The present study evaluated the effects
      of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil
      (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8)
      and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype,
      on male Wistar rats (weighing 250 g at the beginning of the experiments)
      submitted to the elevated T-maze (ETM). The ETM allows the measurement of two
      defensive responses: inhibitory avoidance and one-way escape. In terms of
      psychopathology, these responses have been related to generalized anxiety and
      panic disorder, respectively. Treatment with the EO impaired ETM avoidance
      latencies, without altering escape, in a way similar to the reference drug
      diazepam (P < 0.05) (avoidance 2: control = 84.6 +/- 35.2; EO 12.5 mg/kg = 11.8
      +/- 3.8; EO 25 mg/kg = 14.6 +/- 2.7; diazepam = 7 +/- 2.1). (R)-(-)-carvone also
      significantly altered this same response (P < 0.05; avoidance 1: control = 91.9
      +/- 31.5; carvone = 11.6 +/- 1.8; diazepam = 8.1 +/- 3.3). These results were not
      due to motor changes since no significant effects were detected in an open field.
      These observations suggest that LA exerts anxiolytic-like effects on a specific
      subset of defensive behaviors that have been implicated in generalized anxiety
      disorder, and suggest that carvone is one of the constituents of LA responsible
      for its action as a tranquilizer.

PMID- 22358425
TI  - In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin
      A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot).
AB  - The current in vitro study was designed to investigate the anti-inflammatory,
      cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone
      derivative of known structure isolated from Boesenbergia rotunda. Human
      hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell
      lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL
      68) were used to evaluate the cytotoxicity of BA using the MTT assay. The
      antioxidant activity of BA was assessed by the ORAC assay and compared to
      quercetin as a standard reference antioxidant. ORAC results are reported as the
      equivalent concentration of Trolox that produces the same level of antioxidant
      activity as the sample tested at 20 ug/mL. The toxic effect of BA on different
      cell types, reported as IC50, yielded 20.22 +/- 3.15, 10.69 +/- 2.64, 20.31 +/-
      1.34, 94.10 +/- 1.19, and 9.324 +/- 0.24 ug/mL for A549, PC3, HepG2, HT-29, and
      WRL-68, respectively. BA displayed considerable antioxidant activity, when the
      results of ORAC assay were reported as Trolox equivalents. BA (20 ug/mL) and
      quercetin (5 ug/mL) were equivalent to a Trolox concentration of 11.91 +/- 0.23
      and 160.32 +/- 2.75 uM, respectively. Moreover, the anti-inflammatory activity of
      BA was significant at 12.5 to 50 uM and without any significant cytotoxicity for
      the murine macrophage cell line RAW 264.7 at 50 uM. The significant biological
      activities observed in this study indicated that BA may be one of the agents
      responsible for the reported biological activities of B. rotunda crude extract.

PMID- 22358426
TI  - Mammographic density estimation: one-to-one comparison of digital mammography and
      digital breast tomosynthesis using fully automated software.
AB  - OBJECTIVE: To compare breast density on digital mammography and digital breast
      tomosynthesis using fully automated software. METHODS: Following institutional
      approval and written informed consent from all participating women, both digital
      breast tomosynthesis (DBT) and full-field digital mammography (FFDM) were
      obtained. Breast percentage density was calculated with software on DBT and FFDM.
      RESULTS: Fifty consecutive patients (mean age, 51 years; range, 35-83 years)
      underwent both FFDM and DBT. Using a method based on the integral curve, breast
      density showed higher results on FFDM (68.1 +/- 12.1 for FFDM and 51.9 +/- 6.5
      for DBT). FFDM overestimated breast density in 16.2% (P < 0.0001). Using a method
      based on maximum entropy thresholding, breast density showed higher results on
      FFDM (68.1 +/- 12.1 for FFDM and 51.9 +/- 6.5 for DBT). FFDM overestimated breast
      density in 11.4% (P < 0.0001). There was a good correlation among BI-RADS
      categories on a four-grade scale and the density evaluated with DBT and FFDM (r =
      0.54, P < 0.01 and r = 0.44, P < 0.01). CONCLUSION: Breast density appeared to be
      significantly underestimated on digital breast tomosynthesis. KEY POINTS: Breast
      density is considered to be an independent risk factor for cancer Density can be
      assessed on full-field digital mammography and digital breast tomosynthesis
      Objective automated estimation of breast density eliminates subjectivity
      Automated estimation is more accurate than BI-RADS quantitative evaluation Breast
      density may be significantly underestimated on digital breast tomosynthesis.

PMID- 22358429
TI  - Engineering perspectives in tissue engineering.

PMID- 22358427
TI  - Accuracy and predictive features of FDG-PET/CT and CT for diagnosis of lymph node
      metastasis of T1 non-small-cell lung cancer manifesting as a subsolid nodule.
AB  - OBJECTIVES: To retrospectively evaluate the diagnostic accuracy and predictive
      features of F-18 fluorodeoxyglucose positron emission tomography/ computed
      tomography (FDG-PET/CT) and CT in lymph node (LN) staging of T1 non-small-cell
      lung cancers (NSCLCs) manifesting as subsolid nodules. METHODS: From January 2005
      to May 2011, 160 patients with pathologically proven T1 subsolid NSCLCs with LN
      staging were included in this study. Diagnostic accuracies of FDG-PET/CT and CT
      for LN staging were evaluated. Maximum standardised uptake value (SUVmax) and CT
      features of primary tumours were evaluated to investigate predictive factors for
      LN metastasis. RESULTS: LN metastases were found in nine of the 160 patients
      (5.6%). No LN metastasis was present in patients with a solid proportion <=50%.
      Sensitivity, specificity and accuracy of FDG-PET/CT for LN staging on a per
      patient basis were 11.1%, 86.1% and 81.9%; those of CT were 11.1%, 96.7% and
      91.9%. Among patients with a solid proportion >50%, there were significant
      differences in SUVmax, solid portion size, solid proportion and lesion location
      between patients with and without LN metastasis. Multivariate analysis revealed
      that higher SUVmax, a larger solid proportion and central location were
      independent predictors of LN metastasis. CONCLUSIONS: FDG-PET/CT adds little
      value to CT in the lymph node staging of T1 subsolid NSCLCs. KEY POINTS: Lymph
      node (LN) metastases are important in non-small-cell lung cancer (NSCLC). *
      Positron emission tomography (PET) helps to stage solid NSCLCs. * FDG-PET/CT adds
      little to the LN staging of T1 subsolid NSCLCs. * No LN metastasis in patients
      with a solid proportion <=50%. * LN metastasis is more common in solid and/or
      centrally sited tumours.

PMID- 22358428
TI  - Comparison of FDG-PET/CT and MR with diffusion-weighted imaging for assessing
      peritoneal carcinomatosis from gastrointestinal malignancy.
AB  - OBJECTIVES: To assess the accuracy of FDG-PET/CT and MR with diffusion-weighted
      imaging (MR-DWI) for diagnosing peritoneal carcinomatosis (PC) from
      gastrointestinal malignancies. METHODS: Thirty consecutive patients referred for
      staging of gastrointestinal malignancy underwent FDG-PET/CT and MR-DWI in this
      retrospective study. Extent of PC was characterised by dividing the peritoneal
      cavity into three sites in each patient: right and left supramesocolic areas and
      inframesocolic level (total 90 sites). Presence of PC was confirmed either by
      surgery (18/30) or by follow-up (12/30). RESULTS: PC was confirmed in 19 patients
      (19/30). At a total of 90 sites, 27 showed proven PC. On a patient-based
      analysis, sensitivity, specificity, PPV, NPV and accuracy were respectively 84%,
      73%, 84%, 73% and 80% for PET/CT and 84%, 82%, 89%, 75% and 83% for MR-DWI. On a
      site-based analysis, overall sensitivity and specificity of PET/CT (63%, 90%) and
      MR-DWI (74%, 97%) were not statistically different (P = 0.27). In the
      supramesocolic area, MR-DWI detected more sites involved than PET/CT (7/9 vs.
      4/9). The sensitivities of PET and MR were lower for subcentimetre tumour
      implants (42%, 50%). Interobserver agreement was very good for PET/CT and good
      for MR-DWI. CONCLUSIONS: FDG-PET/CT and MR-DWI showed similar high accuracy in
      diagnosing PC. Both techniques underestimated the real extent of PC because of
      decreased sensitivity for subcentimetre lesions. KEY POINTS: FDG-PET/CT and MR
      DWI showed similar high accuracy for diagnosing peritoneal carcinomatosis. * In
      the supramesocolic area, MR-DWI could be more sensitive than PET/CT. * Both
      techniques showed lower sensitivity for subcentimetre lesions. * Interobserver
      agreement was very good for PET/CT and good for MR-DWI.

PMID- 22358430
TI  - Clinical characteristics of 12 cases of appendiceal diverticulitis: a comparison
      with 378 cases of acute appendicitis.
AB  - PURPOSE: Previous authors have suggested that a diverticulum of the vermiform
      appendix has a higher risk of perforation than acute appendicitis. Therefore,
      this study compared appendiceal diverticulitis with acute appendicitis to explain
      the characteristics of appendiceal diverticulitis. METHODS: Data for this study
      came from a retrospective analysis at the Department of Surgery at Fukuoka
      Tokushukai Hospital from January 2005 to June 2008. Twelve cases of appendiceal
      diverticulitis and 378 cases of acute appendicitis were analyzed. RESULTS: The
      patients with appendiceal diverticulitis were older than those with acute
      appendicitis (42.7 +/- 15.4 vs. 29.1 +/- 17.7; p = 0.009). The white blood cell
      (WBC) level was lower (11332 +/- 4658 vs. 14236 +/- 3861; p = 0.011) and the CRP
      level was higher (8.65 +/- 8.94 vs. 4.34 +/- 6.34, p = 0.022) in those with
      appendiceal diverticulitis than in those with acute appendicitis. A preoperative
      diagnosis for appendiceal diverticulitis was made in 4 out of 12 (33.3%) by
      ultrasonography (US). The perforation rate was higher in appendiceal
      diverticulitis than that in acute appendicitis (33.3 vs. 9.8%; p = 0.009).
      CONCLUSIONS: Appendiceal diverticulitis is more likely to perforate over the
      progression of the clinical course, which would mandate appendectomy when
      appendiceal diverticulitis is detected by US, even if the patient has no severe
      abdominal pain.

PMID- 22358432
TI  - An introduction to Cytotechnology.

PMID- 22358431
TI  - Diagnostic performance of 18F-dihydroxyphenylalanine positron emission tomography
      in patients with paraganglioma: a meta-analysis.
AB  - PURPOSE: The aim of this study was to systematically review and conduct a meta
      analysis of published data about the diagnostic performance of (18)F
      dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with
      paraganglioma (PG). METHODS: A comprehensive computer literature search of
      studies published through 30 June 2011 regarding (18)F-DOPA PET or PET/computed
      tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase
      and Scopus databases. Pooled sensitivity and specificity of (18)F-DOPA PET or
      PET/CT in patients with PG on a per patient- and on a per lesion-based analysis
      were calculated. The area under the receiver-operating characteristic (ROC) curve
      was calculated to measure the accuracy of (18)F-DOPA PET or PET/CT in patients
      with PG. Furthermore, a sub-analysis taking into account the different genetic
      mutations in PG patients was also performed. RESULTS: Eleven studies comprising
      275 patients with suspected PG were included in this meta-analysis. The pooled
      sensitivity of (18)F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence
      interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on
      a per lesion-based analysis. The pooled specificity of (18)F-DOPA PET and PET/CT
      in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95%
      (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was
      0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity
      between the studies about sensitivity of (18)F-DOPA PET or PET/CT was found. A
      significant increase in sensitivity of (18)F-DOPA PET or PET/CT was observed when
      a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB)
      gene mutations was performed. CONCLUSION: In patients with suspected PG (18)F
      DOPA PET or PET/CT demonstrated high sensitivity and specificity. (18)F-DOPA PET
      or PET/CT are accurate methods in this setting. Nevertheless, possible sources of
      false-negative results should be kept in mind. Furthermore, SDHB gene mutations
      could influence (18)F-DOPA PET or PET/CT diagnostic performance.

PMID- 22358433
TI  - Cytological analysis and sorting of a human supernumerary minichromosome.
AB  - In a newborn female, an abnormal karyotype, 46,XX/47,XX,+mar/47,XX,+9, was found
      associated with several malformations. The marker chromosome was present in 70%
      of peripheral blood lymphocytes, and its size appeared to be less than half of
      the smallest chromosomes. Several differential staining methods provided no
      indication as to its origin.Chromosomes isolated from EBV-immortalized
      lymphocytes of the patient were fractionated on a FACS-440. The marker was
      resolved as a sharp peak in the region close to the chromosomal debris: its DNA
      content seemed to be close to 40% of chromosomes 21 and 22.About 580000
      minichromosomes were sorted. In order to optimize cloning conditions, a pilot
      cloning experiment was performed on a pool of sorted chromosomes 9, 10, 11 and
      12.

PMID- 22358434
TI  - Detection of chromosome variation in interphase by in situ hybridization with
      repetitive DNA probes: potential applications to cytogenetic analysis and
      mutagenicity testing.
AB  - Individual chromosomes can be identified by means of in situ hybridization with
      DNA probes for chromosome-specific repetitive sequences. The efficiency and
      sensitivity of the method are strictly dependent on the characteristics of the
      probes and the experimental conditions. Using three probes with different copy
      numbers, we demonstrated that the target chromosomes can be visualized in
      interphase when the homologous sequences are repeated at least 50 times.Possible
      applications of interphase analysis to clinical cytogenetics and mutagenicity
      testing are discussed.

PMID- 22358435
TI  - Non random distribution of lesions induced by deoxyribonuclease I in human
      chromosomes.
AB  - We studied the action of deoxyribonuclease I on human lymphocytes in order to
      determine the localization of the DNAase induced aberrations. Our results
      indicate a non-random distribution of the lesions on chromosome regions which may
      reflect a differential pattern of sensitivity to the enzyme. Furthermore we
      observed a correspondence between the preferential DNAase induced breaks and
      fragile sites that are expressed in lymphocytes maintained in medium without
      folic acid. A possible interpretation of our findings is that the accessibility
      to DNAase and/or the efficiency of the repair systems depend on the chromatin
      structure that influences also the expression of some common fragile sites.

PMID- 22358436
TI  - Localization of amplified CAD genes on rearranged chromosomes of Chinese hamster
      cells.
AB  - Chinese hamster cell lines carrying an amplified CAD region were selected from
      V79,B7 cells by their resistance to N-phosphonacetyl-L-aspartate (PALA). In one
      of the selected cell lines, SP PALA (inf1) (supR) L, an acrocentric chromosome
      with abnormally elongated q arms was identified as a marker for the PALA
      resistant phenotype. The marker chromosome carried a homogeneously staining
      region close to a telomeric nucleolar organizer region. In the same region,
      localization of amplified CAD sequences was demonstrated by in situ
      hybridization. The marker chromosome was found to undergo extensive
      rearrangements. In particular, dicentric chromosomes, occurring with an unusually
      high incidence, were found to originate from end-fusion of two homologous marker
      chromosomes.

PMID- 22358438
TI  - 7q-and loss of a polymorphism for the met oncogene in a patient with
      myelofibrosis.
AB  - The met oncogene is the normal counterpart of a chemically-induced transforming
      gene. The chromosomal localization of met is 7q21-31. In a patient with
      myelofibrosis and an interstitial deletion on 7q, we demonstrate that a Taq I
      polymorphism for the met oncogene is lost in the neoplastic cells, thus
      indicating that the deletion occuring in the long arm of chromosome 7 involves
      the met locus.

PMID- 22358437
TI  - Molecular biology of Philadelphia chromosome in chronic granulocytic leukaemia
      and acute lymphoblastic leukaemia.
AB  - In classical t(9;22) translocation, as observed in chronic granulocytic leukemia
      (CGL), a hybrid DNA unit is produced, including a rearranged PHL gene, previously
      known as bcr (breakpoint cluster region) plus the translocated c-abl gene from
      chromosome 9: a hybrid bcr-abl protein, p210 is formed, with increased tyrosine
      kinase activity. Such DNA rearrangement, with a p210 protein synthesis, is also
      found in cases of Philadelphia-positive acute lymphoblastic leukemia (ALL), but
      in apparently similar cases the bcr gene is not rearranged, and a novel p190 abl
      related protein can be found; c-abl rearrangement has also been observed.It is
      thus established that correlations between cytogenetic and molecular events can
      be found in CGL and ALL, as in other haemopoietic malignancies: translocation and
      possible rearrangement of the c-abl oncogene seem of particular importance in
      this case.

PMID- 22358439
TI  - Increased number of chromosome 7 is related to overexpression of EGF receptor
      gene in human glioblastomas.
AB  - Karyotype and nucleic acid analyses have been performed on glioblastoma-derived
      primary cell lines at early passages. Four out of five cell lines displayed a
      significant increase in copy number of epidermal growth factor (EGF) receptor
      gene, which was related to polisomy of chromosome 7, where the gene is the been
      localized. Since EGF is a potent growth factor for human glial cells, and EGF
      receptor gene is the cellular homologue of the v-erb-B oncogene, we analyzed its
      expression in the tumor cell lines. Our results show that numerical alteration of
      chromosome 7 was constantly associated with overexpression of EGF receptor gene.
      Moreover, the high level of EGF receptor specific transcripts detected in two
      cell lines suggests that deregulation of the transcriptional activity of EGF
      receptor gene also occurred in these tumor cells.

PMID- 22358440
TI  - Localization of viral transforming sequences within marker chromosomes associated
      with tumor formation and progression in a murine fibrosarcoma.
AB  - The low-metastatic RSV-transformed fibrosarcoma line B77-3T3 and its metastatic
      variant AA12, selected in vitro, have been analysed by blot and in situ
      hybridization with v-src and murine c-myc specific probes in order to detect
      molecular rearrangements underlying the transition from the low-metastatic to the
      high-metastatic phenotype. Previous cytogenetic analysis had evidenced that a
      marker chromosome of the parental tumor line (chromosome A) is replaced in the
      metastatic counterpart by a new marker chromosome (chromosome B), possibly arisen
      by duplication of a chromosome A segment, included between two C-positive regions
      (L. Doneda et al., 1985). In situ hybridization on chromosome spreads of the two
      related lines with a (3)H-labelled v-src probe showed that src sequences are
      located within the marker chromosomes A and B, and the percentage of grains over
      the AA12 marker chromosome is always double that found on the B77-3T3 marker.
      These signals were considered to identify v-src sequences as they were found to
      be slightly amplified in the metastatic variant DNA by blot hybridization with
      the v-src probe. As regards the intrachromosomal location of the signals, most
      grains were clustered near the heterochromatic bands, suggesting a possible role
      for heterochromatic sites in tumor formation and evolution. No involvement of the
      A and B marker chromosomes was shown by in situ hybridization experiments with a
      c-myc probe. However the dosage of c-myc sequences was also found to be slightly
      increased in the metastatic variant DNA.

PMID- 22358441
TI  - Activation of double-stranded RNA dependent protein kinase by ribosomal RNA
      precursors.
AB  - Two major changes in RNA metabolism occured in macrophages expressing tumoricidal
      activity: a down regulation of total RNA synthesis and an imbalanced accumulation
      of ribosomal RNA precursors with double stranded secondary structure. The aim of
      this study was to investigate a possible role of endogenous ds rRNA precursors in
      the activation of the dsRNA dependent protein kinase. Using a cell free
      transcription system purified rRNA precursors were obtained from the murine rRNA
      gene. The results indicate that rRNA precursors are potent activators of the
      dsPK. The effects are dose dependent and are not affected by treatment of rRNA
      precursors with proteinase K or RNase A. The treatment with RNase V(1), specific
      for dsRNA, completely abrogates the activity of transcripts. The results suggest
      that endogenous RNA, namely rRNA, could control dsPK activation and it can be
      speculated that dsPK activation may be involved in the control of tumoricidal
      activity by macrophages.

PMID- 22358442
TI  - c-Fos protooncogene expression in human normal peripheral blood leukocytes.
AB  - The aim of this study was to investigate the expression of c-fos protooncogene in
      normal human peripheral blood leukocytes by Northern blot analysis. Unlike
      lymphoid cells, monocytes express appreciable levels of c-fos transcripts.
      Unexpectedly, unlike HL-60 (promyelocytic)-derived granulocytes, freshly isolated
      polymorphonuclear cells (PMN) showed c-fos expression, with higher levels of
      expression then monocytes. The expression of c-fos by PMN was superinduced by
      cycloheximide. When PMN were treated with stimuli known to activate some
      functional activities of these cells (phorbol esters, inactivated streptococci,
      colony-stimulating factors, tumor necrosis factor) the expression of c-fos was
      augmented. The 'constitutive' and inducible expression of c-fos in PMN was also
      detectable after 20 hours of culture. These data show that, among the cells
      belonging to the myelo-monocytic lineage, c-fos expression is not restricted to
      monocytes-macrophages and that data obtained from established cell lines are not
      necessarily representative of fresh normal cells. c-fos expression in PMN may
      play a role in the regulation of mature circulating myelocytes.

PMID- 22358443
TI  - Interspersed repetitive L1 family is differentially transcribed during the murine
      thymus ontogeny.
AB  - Repetitive L1 family in the first LINE (Long Interspersed Element) found in
      mammals. Structural and evolutionary studies demonstrated the capability of this
      family to play a functional role and several examples of L1 transcription have
      been reported in humans and mice especially in tumor cell lines.In this paper a
      general decrease in the L1 transcription level in different murine thymoma cell
      lines transformed by different means as compared to a normal counterpart
      represented by adult thymus is shown. When the same kind of analysis has been
      performed on normal thymus at different stages of differentiation (17th day
      embryos, new born, 30th day after birth) a modulated pattern of L1 transcription
      with a peak in the new born thymus was found. Furthermore, heterogeneous L1
      transcription in all the above cases is demonstrated and its possible functional
      meaning discussed.

PMID- 22358444
TI  - Cytogenetic characterization of a mouse cell line transformed by a bacterial
      plasmid.

PMID- 22358445
TI  - Comparison between an antimetabolic assay and a cytocidal assay for in vitro
      chemosensitivity testing of human tumors.

PMID- 22358446
TI  - T-cell receptor gene rearrangements and expression in normal human large granular
      lymphocytes (LGL) and their pathological expansions.
AB  - The lineage to which normal large granular lymphocytes/natural killer (LGL/NK)
      cells belong is controversial; in fact they share some surface markers and
      functional activities with monocytes, but also with T lymphocytes. The
      relationship of LGL to the T cell lineage by analysis with the T cell receptor (T
      rec) gene has been investigated. Pure preparations of human LGL and their CD11(+)
      CD8(-) and CD11(-) CD8(+) subsets had the Tbeta gene in its unrearranged germline
      configuration. Expression of Talpha and Tbeta genes was not detectable. The
      organization of Tgamma gene, which is of particular importance because it occurs
      early in T cell ontogeny, was also found in its germline configuration.A rare
      type of lymphoproliferative disorder, termed Tgamma-LPD, is characterized by
      expansion of cells very similar to LGL for morphology, phenotype, and functional
      activity. Of 17 patients with Tgamma-LPD studied for T-rec rearrangement, 15
      displayed rearrangement of Tbeta and Tgamma loci and were CD3+ (14/15 had
      monoclonal rearrangement), while 2 cases were in germline configuration and were
      CD3-. Similarly to very small subsets of CD3+ LGL recently described, most Tgamma
      LPD cases are CD3+ and have T-rec genes rearranged. These data suggest that
      either a subset of LGL or a particular step of differentiation may be related to
      the T cell lineage; they also demonstrate that, in contrast to previous views,
      most TgammaLPD are monoclonal, presumably neoplastic, lymphoproliferative
      disorders.

PMID- 22358447
TI  - Molecular cytogenetic analysis of human breast tumors: methylation pattern of the
      HLA-DRalpha gene.

PMID- 22358448
TI  - Studies on the biology, histology and cytogenetics of two sublines of a murine
      ovarian reticular cell sarcoma : Biology of M5 and R16 murine tumor.
AB  - Two sublines of the ovarian reticular cell sarcoma M5 in C57BL mice respond
      differently to cyclophosphamide and other alkylating agents. The subline R16,
      which is resistant to cyclophosphamide, was obtained by treating M5 mice
      repeatedly with this compound and subsequently transplanting the regrowing tumor
      for 16 passages. The R16 subline shows biological characteristics perfectly
      superimposable to those of the parent line and histologically resembles an
      undifferentiated mesenchymal neoplasia with numerous atypical nuclei and
      karyokinetic figures with large necrotic areas. The cytogenetic examination of
      the distribution in the chromosomal number of R16 indicates that this subline may
      be considered a clone of the parent line with a modal class of 35 chromosomes (34
      37) versus a class of 34 (31-37) in the M5 tumor line. The presence of
      metacentric chromosomes characterizes the modal class of the two lines, 23 in the
      R16, and 25 in the M5 tumor lines.

PMID- 22358449
TI  - Cellular and genetic studies in three UV-sensitive Chinese hamster mutants.
AB  - Three UV sensitive (UV(s)) mutants (CHO43RO, CHO423PV, CHO30PV), characterized by
      different levels of reduction in their ability to perform unscheduled DNA
      synthesis (UDS), were analysed for spontaneous and UV-induced frequency of
      chromosomal aberrations and for sensitivity to alkylating agents. The baseline
      frequency of chromosomal aberrations was in the normal range, whereas after UV
      irradiation a positive correlation between the degree of UV sensitivity and the
      rate of chromosomal breakage was observed. Survival experiments after mutagen
      exposure indicated that the UV(s) clones are characterized by different levels of
      hypersensitivity to bifunctional alkylating agents whereas the sensitivity to
      monofunctional alkylating agents is in the normal range. Genetic analysis
      performed by measuring the survival after UV in hybrids produced by fusing UV(s)
      cells with wild-type or UV(s) cells belonging to the six Chinese hamster
      complementation groups, indicated that the three clones carry recessive mutations
      and belong to c.g. 2. These findings suggest that defects in the same gene may
      result in different degrees of phenotypic alterations.

PMID- 22358450
TI  - Genotoxic damage induced by doxorubicin in two human melanoma cell lines.

PMID- 22358451
TI  - Response to DNA-damaging agents in cultured cells from patients with X-linked
      duchenne muscular dystrophy phenotype: male DMD, female DMD, possible carriers.
AB  - Using blood cultures the response to gamma (gamma) radiation was examined in a
      male DMD and his mother, in a female DMD and her mother and in a normal control.
      In a series of experiments chromosome aberrations were determined after 3
      separate gamma-irradiation dose levels: 0, 150, 300 rads. The DMD patients showed
      a response to ionising radiations different from control, in fact the percentage
      of aberrations was lower than the control. In this preliminary study a slight
      difference between normal and possible carriers was also found.

PMID- 22358452
TI  - Lymphocyte clones from old subjects: growing rate and functional activity.
AB  - Old subjects exhibit a decline in circulating T cells and an impaired
      proliferative response to mitogens, plus a relative increase in cells with NK
      phenotype not associated with a concomitant increase in their cytolitic
      activity.In the present study a limiting dilution assay was used to evaluate the
      phenotype, the functional activity and the proliferative capacity of clones
      obtained from peripheral blood lymphocytes of old and young subjects. CD5+ CD8+
      clones from old people showed a significant impairment in their proliferative
      capacity and a decreased lytic activity against K562 and P815-IgG cell lines.

PMID- 22358454
TI  - Separating the wheat from the chaff.

PMID- 22358455
TI  - Redistributional consequences of early childhood intervention.
AB  - Recently, early investment in the human capital of children from socially
      disadvantaged environments has attracted a great deal of attention. Programs of
      such early intervention, aimed at children's health and well-being, are spreading
      considerably in the US and are currently being tested in several European
      countries. In a discrete version of the Mirrlees model with a parents' and a
      children's generation, we model the intra-generational and the inter-generational
      redistributional consequences of such intervention programs. It turns out that
      the parents' generation loses whenever such intervention programs are
      implemented. Furthermore, the rich part of the children's generation always
      benefits. Despite the expectation that early intervention puts the poor
      descendants in a better position, our analysis reveals that the poor among the
      children's generation may even be worse off, if the effect of early intervention
      on their productivity is not large enough.

PMID- 22358456
TI  - Problems of priority change in kidney allocation and beyond.
AB  - Standardized and transparent priority setting in medicine, desirable as it is,
      will generally exacerbate inter-temporal equity problems arising from changes in
      treatment priorities: when can it be fair that the treatment of already waiting
      patients who would have had priority under an established system should be
      postponed (withheld) for an extended period of time to advance the treatment of
      others under a reformed system? The reform of the Eurotransplant system of
      priority setting in kidney allocation (ETKAS), which is in many respects ideal,
      is a case in point. To give due weight to new medical knowledge, waiting time
      after the onset of end state renal failure should change from a priority
      enhancing to a priority-reducing factor. Since those who have gained in priority
      by waiting under the present system would be set back under the new, severe
      problems of transitional justice must be overcome when responding to advances in
      medical knowledge. The paper explores conceptually some possible ways of rule
      change and indicates their general relevance from an ethical and a practical
      point of view for future problems of medical resource allocation under
      transparent, standardized priority-setting rules.

PMID- 22358457
TI  - Molecular subgroups of medulloblastoma: an international meta-analysis of
      transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and
      Group 4 medulloblastomas.
AB  - Medulloblastoma is the most common malignant brain tumor in childhood. Molecular
      studies from several groups around the world demonstrated that medulloblastoma is
      not one disease but comprises a collection of distinct molecular subgroups.
      However, all these studies reported on different numbers of subgroups. The
      current consensus is that there are only four core subgroups, which should be
      termed WNT, SHH, Group 3 and Group 4. Based on this, we performed a meta-analysis
      of all molecular and clinical data of 550 medulloblastomas brought together from
      seven independent studies. All cases were analyzed by gene expression profiling
      and for most cases SNP or array-CGH data were available. Data are presented for
      all medulloblastomas together and for each subgroup separately. For validation
      purposes, we compared the results of this meta-analysis with another large
      medulloblastoma cohort (n = 402) for which subgroup information was obtained by
      immunohistochemistry. Results from both cohorts are highly similar and show how
      distinct the molecular subtypes are with respect to their transcriptome, DNA copy
      number aberrations, demographics, and survival. Results from these analyses will
      form the basis for prospective multi-center studies and will have an impact on
      how the different subgroups of medulloblastoma will be treated in the future.

PMID- 22358459
TI  - A myopathy-related actin mutation increases contractile function.
AB  - Nemaline myopathy (NM) is the most common congenital myopathy and is caused by
      mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3
      (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry
      ACTA1 defects and these particular mutations usually induce substitutions of
      single residues in the actin protein. Despite increasing clinical and scientific
      interest, the contractile consequences of these subtle amino acid substitutions
      remain obscure. To decipher them, in the present study, we originally recorded
      and analysed the mechanics as well as the X-ray diffraction patterns of human
      membrane-permeabilized single muscle fibres with a particular peptide
      substitution in actin, i.e. p.Phe352Ser. Results unravelled an unexpected cascade
      of molecular and cellular events. During contraction, p.Phe352Ser greatly
      enhances the strain of individual cross-bridges. Paradoxically, p.Phe352Ser also
      slightly lowers the number of cross-bridges by altering the rate of myosin head
      attachment to actin monomers. Overall, at the cell level, these divergent
      mechanisms conduct to an improved steady-state force production. Such results
      provide new surprising scientific insights and crucial information for future
      therapeutic strategies.

PMID- 22358458
TI  - Subgroup-specific alternative splicing in medulloblastoma.
AB  - Medulloblastoma comprises four distinct molecular variants: WNT, SHH, Group 3,
      and Group 4. We analyzed alternative splicing usage in 14 normal cerebellar
      samples and 103 medulloblastomas of known subgroup. Medulloblastoma samples have
      a statistically significant increase in alternative splicing as compared to
      normal fetal cerebella (2.3-times; P < 6.47E-8). Splicing patterns are distinct
      and specific between molecular subgroups. Unsupervised hierarchical clustering of
      alternative splicing events accurately assigns medulloblastomas to their correct
      subgroup. Subgroup-specific splicing and alternative promoter usage was most
      prevalent in Group 3 (19.4%) and SHH (16.2%) medulloblastomas, while observed
      less frequently in WNT (3.2%), and Group 4 (9.3%) tumors. Functional annotation
      of alternatively spliced genes reveals overrepresentation of genes important for
      neuronal development. Alternative splicing events in medulloblastoma may be
      regulated in part by the correlative expression of antisense transcripts,
      suggesting a possible mechanism affecting subgroup-specific alternative splicing.
      Our results identify additional candidate markers for medulloblastoma subgroup
      affiliation, further support the existence of distinct subgroups of the disease,
      and demonstrate an additional level of transcriptional heterogeneity between
      medulloblastoma subgroups.

PMID- 22358460
TI  - A fluorescence "turn-on" chemodosimeter for Cu2+ in aqueous solution based on the
      ion promoted oxidation.
AB  - We developed a novel method for Cu(2+) detection based on the ion promoted
      oxidation reaction. Chemodosimeter L (weak fluorescence) can be oxidized into 3
      benzothiazoly-7-N,N-diethylaminocoumarin (strong green fluorescence, coumarin 6)
      by Cu(2+) with high selectivity and sensitivity in HEPES (10 mM, pH = 7.4) buffer
      containing 50% (v/v) water-CH(3)CN solution.

PMID- 22358461
TI  - Left heart bypass support with the Rotaflow Centrifugal Pump(r) as a bridge to
      decision and recovery in an adult.
AB  - Since left heart bypass or biventricular circulatory assist with an
      extracorporeal centrifugal pump as a bridge to decision or recovery sometimes
      requires long-time support, the long-term durability of extracorporeal
      centrifugal pumps is crucial. The Rotaflow Centrifugal Pump((r)) (MAQUET
      Cardiopulmonary AG, Hirrlingen, Germany) is one of the centrifugal pumps
      available for long-term use in Japan. However, there have been few reports of
      left heart bypass or biventricular circulatory support over the mid-term. This is
      a case report of left heart bypass support with the Rotaflow Centrifugal
      Pump((r)) as a bridge to decision and recovery for an adult patient who could not
      be weaned from cardiopulmonary bypass and percutaneous cardiopulmonary support
      after cardiac surgery. We could confirm that the patient's consciousness level
      was normal; however, the patient could not be weaned from the left heart bypass
      support lasting 1 month. Therefore, the circulatory assist device was switched to
      the extracorporeal Nipro ventricular assist device (VAD). This time, left heart
      bypass support could be maintained for 30 days using a single Rotaflow
      Centrifugal Pump((r)). There were no signs of hemolysis during left heart bypass
      support. The Rotaflow Centrifugal Pump((r)) itself may be used as a device for a
      bridge to decision or recovery before using a VAD in cardiogenic shock patients.

PMID- 22358462
TI  - ESACT/JAACT Meeting 1994 Program and Abstracts.

PMID- 22358463
TI  - Assessment of heterologous membrane protein polarity in transiently transfected
      MDCK cells.
AB  - We have evaluated transient transfection of MDCK cells by the DEAE
      dextran/chloroquine method as a rapid method for study of heterologous plasma
      membrane protein polarity. Transiently transfected cells reseeded onto permeable
      supports formed confluent monolayers with normal tight junctions and normal
      distribution of endogenous apical and basolateral surface markers. Transfected
      monolayers reseeded onto opaque polycarbonate filters attained cell heights 3
      times greater than on transparent filters. Conventional and confocal
      immunofluorescence microscopy were used to assess polarity of transient
      expression of heterologous proteins previously defined in stably transfected cell
      lines as apical (DAF-CD55), basolateral (VSV-G), and nonpolarized (CD7) in
      distribution. Through each transiently expressed protein exhibited a polarity
      phenotype in most cells which resembled the stable phenotype, consistency of
      polarized localization was less than in stably transfected cells. Similar results
      were obtained by lipofection. We conclude that transient transfection of MDCK
      cells may be useful as a rapid screen, but is not sufficiently reliable for
      definitive assessment of heterologous membrane proein polarity.

PMID- 22358464
TI  - The effects of oncogene transfection on growth and antibody production of human
      mouse heterohybridomas.
AB  - Human-mouse heterohybridomas producing human monoclonal antibodies show slower
      growth rates and lower peak cell densities than murine hybridomas. In order to
      improve the growth properties we transfected a heterohybridoma cell line with
      expression plasmids containing the oncogenes v-src, c-Ha-ras and SV40largeT. The
      plasmids were transferred by electroporation. Growth promoting activities of the
      plasmids were proven in NIH3T3 cells whereby a doubling of the maximum cell
      densities of this cell type was observed. The oncogene products were analyzed by
      means of northern blotting and immunofluorescence. After transfection of c-src
      and c-ras, a heterohybridoma cell line was derived which showed improved growth
      characteristics compared to the original cell line. Although specific antibody
      production was lower, antibody concentrations which accumulated in batch culture
      were higher due to increased maximum cell densities.

PMID- 22358465
TI  - Induction of stress proteins in anoxic and hyperthermicSpodoptera frugiperda
      cells.
AB  - In this study, we compare stress protein induction in anoxic and
      hyperthermicSpodoptera frugiperda cells. Anoxia transiently induces a cluster of
      heat shock proteins at 71 and 72 kDa. This is a subset of a larger group of
      stress proteins induced by heat shock. Several heat shock proteins reported in
      this study were previously undetected inS. frugiperda. With these additional
      proteins, the stress response of hyperthermicS. frugiperda closely resembles that
      ofDrosophila melanogaster. Prior investigations of stress protein induction
      during oxygen deprivation focused on mammalian cells. In sharp contrast to these
      cells, anoxicS. frugiperda cells neither induce glucose-regulated proteins nor
      suppress the heat shock family of 71/72 kDa proteins. These findings provide
      insight into the virtually unexplored area of stress protein induction in anoxic
      insect cells. In addition, they help to explain the effects of oxygen deprivation
      on heterologous protein yield from virally infected insect cells and to develop
      an oxygenregulated promoter for stably transformed insect cells.

PMID- 22358466
TI  - Enhanced productivity of Protein C by recombinant human cells in automated fed
      batch cultures.
AB  - Recombinant human kidney cells, 293, were cultivated in serum-free fed-batch
      cultures for the production of Protein C. By coupling the feeding of concentrated
      medium to pH control based on established stoichiometric relations, the titer of
      Protein C increased by more than ten fold as compared to batch culture, even
      though the total cell concentration increased only by less than two fold. Such a
      fed-batch culture is a simple system for enhancing the productivity of mammalian
      cells in culture.

PMID- 22358467
TI  - Effects of organic pH buffers on a cell growth and an antibody production of
      human-human hybridoma HB4C5 cells in a serum-free culture.
AB  - Human-human hybridoma cells secreting a human monoclonal antibody were cultured
      in a serum-free medium containing various organic pH buffers in order to clarify
      their effects on cell growth and antibody production. Organic pH buffers having
      either one sulfonic acid and several acyclic amine moieties, or several cyclic
      amine moieties containing two amino nitrogen did not inhibit cell growth; while
      other organic buffers sulfonic acid moiety plus several cyclic amine moieties
      containing one amino nitrogen slightly decreased cell growth, but enhanced
      antibody production. Using Fujita's organic conceptual diagram, a relationship
      between the organicity and inorganicity of a pH buffer to cell growth and
      antibody production was found. pH buffers with large inorganicity and small
      organicity values were favorable for cell growth, and buffers with small
      inorganicity and large organicity values were preferred to enhance antibody
      production. Although the pH buffering range affects cell growth, its effect on
      antibody production is not clear. In conclusion, 2-morpholinoethanesulfonic acid
      (MES), 3-morpholino-propanesulfonic acid (MOPS) and 1, 2-N, N'-bis[N", N'''-di(2
      sulfonoethyl)piperazinyl]ethane (Bis-PIPES) are shown to be the most optimal of
      the buffers tested, because they enhanced antibody production without decreasing
      the cell growth among the pH buffers tested here.

PMID- 22358468
TI  - Separation of intact and damaged hepatocytes in sucrose following non-enzymatic
      liver perfusion.
AB  - This study deals with isolation of rat hepatocytes by a non-enzymatic method and
      the separation of intact and damaged cells in sucrose medium. Low speed
      centrifugation in isotonic sucrose medium of a hepatocyte suspension obtained by
      mechanical desaggregation of liver pre-perfused with EDTA solution results in the
      formation of a cell pellet which contains two different layers. A darker layer
      contains hepatocytes with intact plasma membranes. Their respiratory activity and
      xenobiotic metabolism are close to those of the cells isolated by collagenase
      perfusion. The study of distribution of lipophilic cation tetraphenylphosphonium
      (TPP(+)) indicates a predominantly mitochondrial localization of TPP(+) in the
      intact cells following non-enzymatic and collagenase isolation. Hepatocytes in
      the upper layer have damaged plasma membranes. As a result they lose the
      potential to accumulate TPP(+), and have low rates of endogenous respiration and
      biotransformation activity. Addition of exogenous NADPH restores the capability
      to metabolize xenobiotics. Washing and incubation of these hepaticytes in an
      intracellular type medium results in restoration of uncoupler-stimulated oxygen
      consumption and generation of membrane potential in the presence of a succinate
      substrate. These properties are close to those of hepatocytes permeabilized by
      digitonin treatment. Thus, the procedure allows the simultaneous isolation of
      both intact and permeabilized hepatocytes with functionally active intracellular
      structures without the use of relatively expensive chemicals such as collagenase
      and Percoll.

PMID- 22358469
TI  - Expanding the regioselective enzymatic repertoire: oxidative mono-cleavage of
      dialkenes catalyzed by Trametes hirsuta.
AB  - The first report of a biocatalytic regioselective oxidative mono-cleavage of
      dialkenes was successfully achieved employing a cell-free enzyme preparation from
      Trametes hirsuta at the expense of molecular oxygen. Selected reactions were
      performed on a preparative scale affording high to excellent conversions and
      chemoselectivities.

PMID- 22358470
TI  - Development and characterization of insect cell lines.
AB  - CONCLUSIONS: With the wide availability of insect cell culture media, it can
      generally be considered a routine process to develop new cell lines. Exceptions
      to this statement do exist, of course. Difficulties may arise when attempting to
      culture a specific cell type. For example, while there are a few cell lines from
      insect fat body and at least one from the midgut, it may not be possible to
      obtain cell lines from these tissues from all insect species due to terminal
      differentiation and other factors. Also, researchers have desired cell lines from
      certain species, such as the honey bee, for which no success has been obtained.
      As in the early days of tissue culture, it is difficult to discern why negative
      results occur. However, as more is learned about the physiology and nutrition of
      various insects and tissues, we may get clues which will help solve these
      questions.The remaining chapters in this book will provide the reader with
      exciting uses for insect cell culture. As I mentioned earlier, the baculovirus
      expression vector system has provided a stimulus to the field of insect cell
      culture not seen previously.

PMID- 22358471
TI  - New approaches to insect tissue culture.
AB  - CONCLUSION: Current methods of insect cell culture have produced a limited
      variety of cell types in an ever expanding list of insect cell lines. In
      developing midgut epithelial cell lines, we found that traditional methods in
      insect cell culture failed to provide healthy cells from mature tissues.
      Examination of mammalian cell culture literature for this particular cell type
      provided the insight required to successfully develop a cell-specific line
      (Baines et al., 1994). The potential applications for cell-specific lines from
      insects are numerous. This paper is a compilation of ideas that will hopefully
      enable other researchers to develop additional cell-specific lines.

PMID- 22358472
TI  - Insect cell physiology.

PMID- 22358473
TI  - Insect cell cultivation: growth and kinetics.

PMID- 22358474
TI  - Medium design for insect cell culture.

PMID- 22358476
TI  - Construction of baculovirus recombinants.

PMID- 22358477
TI  - Passage effect of virus infection in insect cells.

PMID- 22358475
TI  - Replication patterns and cytopathology of cells infected with baculoviruses.
AB  - CONCLUSION: In vitro studies have contributed greatly to an understanding of
      viral cytopathology, molecular biology, and pathogenesis. A model of the role of
      baculoviruses in a host-parasite relationship is developing which reveals the
      virus as gaining control of many aspects of host cell biology including control
      of the cell replication machinery (apoptotic response, macromolecular synthesis),
      the cytoskeletal structure, the nuclear membrane and intranuclear architecture.
      Baculovirus replication is a collection of independent but inter-related
      processes which work within the framework of the host cell, with the in vivo goal
      of maximizing production of progeny virions. Further molecular dissection of
      baculovirus replication should yield insight into the processes and principles of
      viral and host regulatory systems, perhaps facilitating development of new
      generations of high efficiency sub-viral expression vector systems and the
      development of genetically improved strains of virus safe for field use in
      ecologically based pest management strategies.

PMID- 22358478
TI  - Post-translational modifications in insect cells.

PMID- 22358479
TI  - Productivity of insect cells for recombinant proteins.

PMID- 22358481
TI  - Shear sensitivity of insect cells.
AB  - CONCLUSIONS: While insect cells can be easily damaged in bioreactors as a result
      of hydrodynamic forces, it is also relatively easy to prevent this damage. Of
      several possible damage mechanisms, the best understood and preventable is the
      attachment of cells to gas-liquid interfaces and the subjection of these attached
      cells to the hydro-dynamic forces and/or physical forces associated with these
      interfaces. For example, cells attached to gas bubbles in a bioreactor can be
      transported into the foam layer where they are physically removed from the cell
      suspension, or they can be killed when the gas bubble they are attached to
      ruptures at the medium-air interface at the top of the bioreactor. The easiest
      method to prevent this damage is through the use of specific surface active
      compounds, such as Pluronic F-68 or Methocel E-50 which prevent the cells from
      attaching to the gas-medium interface.

PMID- 22358482
TI  - Insect cell bioreactors.

PMID- 22358480
TI  - Chaperone and foldase coexpression in the baculovirus-insect cell expression
      system.
AB  - CONCLUSIONS: The BEVS has become widely utilized for production of recombinant
      proteins. However, protein aggregation and inefficient processing often limit
      yields, especially for secreted and membrane proteins. Since many proteins of
      pharmaceutical interest require similar posttranslational processing steps,
      engineering the folding, assembly, and secretion pathway may enhance the
      production of a wide variety of valuable complex proteins. Efforts should be
      undertaken to coexpress the relevant chaperones or foldases at low levels in
      concert with the final product to ensure the ideal folding and assembly
      environment. In the future, expression of oligosaccharide modifying enzymes and
      secretion factors may further improve secretion rates of assembled proteins and
      provide heterologous proteins with altered glycoforms. Also significant is the
      use of BEVS as an in vivo eucaryotic laboratory to study the fundamental roles of
      differnt chaperones, foldases, and secretion factors. The coexpression of
      chaperones and foldases will complement other approaches such as the development
      of alternative insect cell lines, promoters, and signal peptides to optimize the
      baculovirus-insect cell expression system for generating high yields of valuable
      proteins.

PMID- 22358483
TI  - Perfusion bioreactors for the production of recombinant proteins in insect cells.
AB  - CONCLUSION: High density perfusion culture of insect cells for the production of
      recombinant proteins has proved to be an attractive alternative to batch and fed
      batch processes. A comparison of the different production processes is summarized
      in Table 3. Internal membrane perfusion has a limited scale-up potential but
      appears to the method of choice in smaller lab-scale production systems. External
      membrane perfusion results in increased shear stress generated by pumping of
      cells and passing through microfiltration modules at high velocity. However,
      using optimized perfusion strategies this shear stress can be minimized such that
      it is tolerated by the cells. In these cases, perfusion culture has proven to be
      superior to batch production with respect to product yields and cell specific
      productivity. Although insect cells could be successfully cultivated by
      immobilization and perfusion in stationary bed bioreactors, this method has not
      yet been used in continuous processes. In fluidized bed bioreactors with
      continuous medium exchange cells showed reduced growth and protein production
      rates.For the cultivation of insect cells in batch and fedbatch processes
      numerous efforts have been made to optimize the culture medium in order to allow
      growth and production at higher cell densities. These improved media could be
      used in combination with a perfusion process, thus allowing substantially
      increased cell densities without raising the medium exchange rate. However,
      sufficient oxygen supply has to be guaranteed during fermentation in order to
      ensure optimal productivity.

PMID- 22358484
TI  - Immobilization of insect cells.

PMID- 22358485
TI  - Modelling baculovirus infection of insect cells in culture.
AB  - CONCLUSIONS: Infection of insect cells with baculovirus is a potentially
      attractive means for producing both viral insecticides and recombinant proteins.
      The continuation of mathematical modelling studies such as those reviewed in this
      paper are essential in order to realise the full potential of the system. Through
      mathematical models it is possible to predict complex behaviours such as those
      observed when infecting cells at low MOI or when propagating virus in a
      continuous culture system. A purely empirical analysis of the same phenomena is
      very difficult if not impossible.The present three models are - despite their
      complexity and the effort that has gone into developing them - all first
      generation models. They summarise, to a large extent, our present quantitative
      understanding of the interaction between baculovirus and insect cells, when
      looked upon as a black box system. The binding and initial infection processes
      are still quantitatively poorly understood and further work in this area is much
      needed. On the longer term, a second generation of models is likely to consider
      interior processes such as viral DNA and RNA accumulation in much more detail
      using a structured model of the infection cycle.

PMID- 22358486
TI  - Scale up aspects of sparged insect-cell bioreactors.
AB  - CONCLUSION: In this chapter we have attempted to evaluate the most important
      parameters which can be useful for the pur-pose of design and scale up. Insect
      cells and animal cells in general can be grown well in large vessels. However,
      none of the theories and parameters discussed in this chapter have been validated
      on a larger scale than laboratory and small pilot reactors. Selection of the most
      suitable design and scale-up method there-fore needs in particular studies in
      larger vessels. The Kolmogorov theory and the killing-volume model are in this
      respect the most promising approaches for the optimal design of large-scale
      animal-cell bioreactors.

PMID- 22358487
TI  - Oxygen gradients in small and big sparged insect-cell bioreactors.
AB  - CONCLUSIONS: It should be clear from the above that the calculations described
      here are at best rough estimations yielding order-of-magnitude values. Even
      though, the following general conclusions can be drawn. The gradients in stagnant
      layers surrounding the particles which are characteristic for animal-cell
      bioreactors are relatively small as compared to the gradients which can be
      expected in the bulk-liquid phases of the three bioreactors considered, in
      particular to the gradients in the stagnant layer surrounding the air bubbles. It
      can be concluded that under almost all circumstances gradients are likely to
      exist and can be very steep in larger vessels and in particular at high cell
      densities. The effects of gradients, however, are largely unknown; therefore
      research on the effects of gradients on specific and volumetric productivities
      and product quality seems to be an interesting area.

PMID- 22358489
TI  - Parvovirus diagnostics and vaccine production in insect cells.

PMID- 22358488
TI  - Downstream processing of insect cell cultures.

PMID- 22358490
TI  - Classical swine fever virus diagnostics and vaccine production in insect cells.

PMID- 22358492
TI  - Economics of baculovirus-insect cell production systems.
AB  - CONCLUSIONS: Commercial production of pharmaceutical proteins in baculovirus -
      insect cell systems is already a reality, and has therefore not been discussed in
      detail here. Cost-efficacy will depend on the productivity of the protein in
      culture, the dose, and the quantities required. According to the model described
      here, cost-effective production of baculoviruses for use in agriculture should
      also be feasible, assuming the commercial availability of a low-cost medium,
      together with a baculovirus with high productivity in cell culture, which is
      effective at a field application rate of 10(12) PIB ha(-1) or lower. All of these
      criteria appear to be achievable, given fairly modest advances over currently
      available technology. Given the relatively high fixed costs associated with
      production of baculoviruses on an agricultural scale in bioreactors however,
      profitability will depend on the scale of production. A substantial market
      opportunity (perhaps in the order of 1 million hectares) would be necessary in
      order to exploit the economies of scale achievable with baculovirus -insect cell
      production systems.

PMID- 22358491
TI  - Production of multidomain complement glycoproteins in insect cells.

PMID- 22358493
TI  - Safety aspects of insect cell culture.
AB  - CONCLUSIONS: The hazards posed to the environment by the accidental release of
      baculovirus expression vectors can be put into perspective by the results
      obtained from experiments in which AcNPV was released deliberately into the field
      (Bishop et al., 1992). Polyhedrin positive viruses will persist in soil and on
      leaf surfaces for periods comprising weeks and months. However, polyhedrin
      negative viruses (similar to those used as expression vectors) do not survive in
      similar situations. In consequence, accidental release of baculovirus expression
      vectors poses negligible hazard. The risk of such a release will largely depend
      on the skill of the operators. This does not take into account the hazard posed
      by the recombinant product which is being made by the virus-infected insect cell.
      Synthesis of a mammalian-specific toxin, of course, would require particularly
      careful manipulation of the virus-infected cell culture.The fact that insect cell
      lines represent an undefined risk, in terms of carriage of adventitious agents
      means that their containment should be maintained at a minimum of the European
      containment level 2. Where the tissue of origin has a high risk of infection with
      human pathogens or where cells may have been used in a virus culture laboratory
      then appropriate testing is advisable. Careful risk assessment respecting the
      scale of work and whole procedures (in addition to individual assessment of
      agents and reagents) will ensure safe working conditions for laboratory staff. If
      applied properly safety procedures will also succeed in encouraging clean,
      efficient and well documented work procedures which are synonymous with the
      economical use of time and resources and good science.

PMID- 22358494
TI  - Regulatory issues in the use of insect-cell culture.
AB  - CONCLUSION: The insect cell as host for protein production is relative new.
      Therefore few data are available. This creates a vicious circle because it makes
      the choice of insect cells as basis for a pharmaceutical process less attractive.
      There are three main issues when comparing insect-cells to "traditional" systems
      as mammalian and bacterial cells. First, since the expression vector is not
      incorporated in the cells, a virus stock similar to the cell bank system has to
      be laid down and tested. This will cost time and money. Secondly the vector is
      subject to mutation and therefore the decrease in infectivity has to be
      characterized and validated. Third, the post-translational modification of the
      protein may differ. None of the mentioned issues, however, forms an obstacle that
      can not be overcome.

PMID- 22358495
TI  - Preface.

PMID- 22358496
TI  - Abstracts of oral and poster presentation.

PMID- 22358498
TI  - Transvaginal laparo-endoscopic single-site sigmoidectomy.
AB  - We report a case of sigmoid colon resection by single-incision laparoscopic
      surgery using transvaginal access. The patient was a 54-year-old woman with early
      stage sigmoid cancer who had no previous surgery and had a body mass index of
      23.5 kg/m(2). The operative time was 270 min, and the blood loss was negligible.
      We used only transvaginal access, since no transabdominal assistance was
      required. No complications occurred. Minimal postoperative pain and a rapid
      recovery of gastrointestinal function were observed. As novel equipment is
      introduced into clinical practice, transvaginal laparoscopic procedures will most
      likely become increasingly popular in abdominal surgery. In particular, this type
      of procedure will have a more defined role in colorectal surgery. Indeed, in the
      future, it may become an alternative for natural orifice transluminal endoscopic
      surgery.

PMID- 22358497
TI  - Estrogen-dependent regulation of sodium/hydrogen exchanger-3 (NHE3) expression
      via estrogen receptor beta in proximal colon of pregnant mice.
AB  - Although constipation is very common during pregnancy, the exact mechanism is
      unknown. We hypothesized that the involvement of estrogen receptor (ER) in the
      regulation of electrolyte transporter in the colon leads to constipation. In this
      study, the intestines of normal female ICR mouse and pregnant mice were examined
      for the expression of ERalpha and ERbeta by immunohistochemistry and in situ
      hybridization. ERbeta, but not ERalpha, was expressed in surface epithelial cells
      of the proximal, but not distal, colon on pregnancy days 10, 15, and 18, but not
      day 5, and the number of ERbeta-positive cells increased significantly during
      pregnancy. Expression of NHE3, the gene that harbors estrogen response element,
      examined by immunohistochemistry and western blotting, was localized in the
      surface epithelial cells of the proximal colon and increased in parallel with
      ERbeta expression. In ovariectomized mice, NHE3 expression was only marginal and
      was up-regulated after treatment with 17beta-estradiol (E(2)), but not E(2) + ICI
      182,780 (estrogen receptor antagonist). Moreover, knock-down of ERbeta expression
      by electroporetically transfected siRNA resulted in a significant reduction of
      NHE3 expression. These results indicate that ERbeta regulates the expression of
      NHE3 in the proximal colon of pregnant mice through estrogen action, suggesting
      the involvement of increased sodium absorption by up-regulated NHE3 in
      constipation during pregnancy.

PMID- 22358500
TI  - New expectations from the well-known medicinal properties of Arctium lappa.
AB  - AMP-activated protein kinase (AMPK) serves as a major regulator of energy
      homeostasis and is activated by different glucose-lowering agents. Indeed, AMPK
      has been identified as an attractive target for the development of innovative
      molecules to treat type 2 diabetes. In this issue of Diabetologia (doi:
      10.1007/s00125-011-2366-3 ), Huang and co-workers report that arctigenin
      activates muscle uptake of glucose and inhibits hepatocyte gluconeogenesis and
      lipogenesis by reducing mitochondrial respiration and inducing AMPK activity.
      Importantly, it is reported that arctigenin improves glucose and lipid metabolism
      in ob/ob mice. Based on this evidence, Huang and co-workers suggest that
      arctigenin may represent a valuable lead compound for developing innovative
      glucose-lowering molecules. While these findings are not entirely novel and
      mechanistic investigations are needed, the results strongly support the concept
      that arctigenin deserves to be further considered because of its several
      potentially beneficial in vivo effects. In particular, the authors conclude that
      further mechanistic studies on arctigenin might provide novel insight and
      opportunities for selective modulation of subcutaneous and visceral fat mass.

PMID- 22358501
TI  - Mechanisms of olfactory signal reception and transduction : Introduction.

PMID- 22358499
TI  - Obstacles on the way to the clinical visualisation of beta cells: looking for the
      Aeneas of molecular imaging to navigate between Scylla and Charybdis.
AB  - For more than a decade, researchers have been trying to develop non-invasive
      imaging techniques for the in vivo measurement of viable pancreatic beta cells.
      However, in spite of intense research efforts, only one tracer for positron
      emission tomography (PET) imaging is currently under clinical evaluation. To many
      diabetologists it may remain unclear why the imaging world struggles to develop
      an effective method for non-invasive beta cell imaging (BCI), which could be
      useful for both research and clinical purposes. Here, we provide a concise
      overview of the obstacles and challenges encountered on the way to such BCI, in
      both native and transplanted islets. We discuss the major difficulties posed by
      the anatomical and cell biological features of pancreatic islets, as well as the
      chemical and physical limits of the main imaging modalities, with special focus
      on PET, SPECT and MRI. We conclude by indicating new avenues for future research
      in the field, based on several remarkable recent results.

PMID- 22358507
TI  - Mouse genetics 2011: meeting report.

PMID- 22358508
TI  - The shoot is important for high-affinity nitrate uptake in Egeria densa, a
      submerged vascular plant.
AB  - To understand the mechanisms of nitrate uptake by submerged vascular plants, a
      cDNA for a high-affinity nitrate transporter, NRT2, was isolated from Egeria
      densa, a submerged monocot. The deduced EdNRT2 protein was similar to the
      proteins of a conserved NRT2 group in higher plants. Real-time reverse
      transcription-PCR analysis revealed that after feeding whole plants with 0.2 mM
      nitrate, the EdNRT2 transcripts were induced in both shoots and roots within 0.5
      h, reached the maximum by 1-3 h and then decreased. The EdNRT2 transcript levels
      in shoots were comparable to those in roots. When nitrate was applied separately
      to shoots and roots, the EdNRT2 transcripts were induced only in nitrate-treated
      organs and reached the maximum levels comparable to those in organs when nitrate
      was applied to whole plants. (15)N-nitrate feeding experiments demonstrated that
      both shoots and roots are responsible for nitrate uptake and that biomass and
      (15)N content in shoots was even higher than that in roots. We concluded that
      EdNRT2 is involved in high-affinity nitrate uptake by shoots and roots of E.
      densa, that nitrate is taken up independently by shoots and roots and that shoots
      play an important role in nitrate uptake from aquatic ecosystem.

PMID- 22358509
TI  - Molecular links between mitochondrial dysfunctions and schizophrenia.
AB  - Schizophrenia is a complex neuropsychiatric disorder with both neurochemical and
      neurodevelopmental components in the pathogenesis. Growing pieces of evidence
      indicate that schizophrenia has pathological components that can be attributable
      to the abnormalities of mitochondrial function, which is supported by the recent
      finding suggesting mitochondrial roles for Disrupted-in-Schizophrenia 1 (DISC1).
      In this minireview, we briefly summarize the current understanding of the
      molecular links between mitochondrial dysfunctions and the pathogenesis of
      schizophrenia, covering recent findings from human genetics, functional genomics,
      proteomics, and molecular and cell biological approaches.

PMID- 22358510
TI  - A MAP kinase pathway is implicated in the pseudohyphal induction by hydrogen
      peroxide in Candica albicans.
AB  - Hydrogen peroxide (H(2)O(2)) functions as a ubiquitous intracellular messenger
      besides as an oxidative stress molecule. This dual role is based on the distinct
      cellular responses against different concentrations of H(2)O(2). Previously, we
      demonstrated that both low (> 1 mM) and high (4-10 mM) doses of exogenous
      H(2)O(2) induce filamentous growth with distinct cell morphology and growth rate
      in Candida albicans, suggesting the different transcription response. In this
      study, we revealed that the sub-toxic and toxic levels of H(2)O(2) indeed induced
      pseudohyphae, but not true hyphae. Supporting this, several hyphae-specific genes
      that are expressed in true hyphae induced by serum were not detected in either
      sub-toxic or toxic H(2)O(2) condition. A DNA microarray analysis was conducted to
      reveal the transcription profiles in cells treated with sub-toxic and toxic
      conditions of H(2)O(2). Under the sub-toxic condition, a small number of genes
      involved in cell proliferation and metabolism were up-regulated, whereas a large
      number of genes were up-regulated in the toxic condition where the genes required
      for growth and proliferation were selectively restricted. For pseudohyphal
      induction by sub-toxic H(2)O(2), Cek1 MAPK activating the transcription factor
      Cph1 was shown to be important. The absence of expression of several hyphae
      specific genes known to be downstream targets of Cph1-signaling pathway for true
      hyphae formation suggests that the Cek1-mediated signaling pathway is not solely
      responsible for pseudohyphal formation by subtoxic H(2)O(2) and, but instead,
      complex networking pathway may exists by the activation of different regulators.

PMID- 22358511
TI  - Moesin is a biomarker for the assessment of genotoxic carcinogens in mouse
      lymphoma.
AB  - 1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have
      been widely used in industry. To identify a specific biomarker for these
      carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells
      treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2
      DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater
      than 1.5-fold increase or decrease in intensity compared to control cells on a 2
      D gel, we focused on the candidate biomarker moesin. Western analysis using
      monoclonal rabbit anti-moesin confirmed the identity of the protein and its
      increased level of expression upon exposure to the carcinogenic compounds. Moesin
      expression also increased in cells treated with six additional genotoxic
      carcinogens, verifying that moesin could serve as a biomarker to monitor
      phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma
      cells.

PMID- 22358513
TI  - Hiroki Murakami Memorial Issue, preface by the Editors.

PMID- 22358512
TI  - A mutational study of Cnu reveals attractive forces between Cnu and H-NS.
AB  - Cnu is a small 71-amino acid protein that complexes with H-NS and binds to a
      specific sequence in the replication origin of the E. coli chromosome. To
      understand the mechanism of interaction between Cnu and H-NS, we used bacterial
      genetics to select and analyze Cnu variants that cannot complex with H-NS. Out of
      2,000 colonies, 40 Cnu variants were identified. Most variants (82.5%) had a
      single mutation, but a few variants (17.5%) had double amino acid changes. An in
      vitro assay was used to identify Cnu variants that were truly defective in H-NS
      binding. The changes in these defective variants occurred exclusively at charged
      amino acids (Asp, Glu, or Lys) on the surface of the protein. We propose that the
      attractive force that governs the Cnu-H-NS interaction is an ionic bond, unlike
      the hydrophobic interaction that is the major attractive force in most proteins.

PMID- 22358514
TI  - Memories of professor hiroki murakami.

PMID- 22358515
TI  - Changes in monoclonal antibody productivity of recombinant BHK cells immobilized
      in collagen gel particles.
AB  - Animal cell perfusion high density culture is often adopted for the production of
      biologicals in industry. In high density culture sometimes the productivity of
      biologicals has been found to be enhanced. Especially in immobilized animal cell
      culture, significant increase in the productivity has been reported. We have
      found that the specific monoclonal antibody (MAb) productivity of an immobilized
      hybridoma cell is enhanced more than double. Several examples of enhancing
      productivities have been also shown by collagen immobilized cells. Immobilized
      cells involve some different points from non-immobilized cells in high density
      culture: In immobilized culture, some cells are contacted together, resulting in
      locally much higher cell concentration more than 10(8) cells/ml. Information
      originating from a cell can be easily transduced to the others in immobilized
      culture because the distance between cells is much nearer. Here we have performed
      collagen gel immobilized culture of recombinant BHK cells which produce a human
      IgG monoclonal antibody in a protein-free medium for more than three months. In
      this high density culture a stabilized monoclonal antibody production was found
      with around 8 times higher specific monoclonal antibody productivity compared
      with that in a batch serum containing culture. No higher MAb productivity was
      observed using a conditioned medium which was obtained from the high density
      culture, indicating that no components secreted from the immobilized cells work
      for enhancing monoclonal antibody production. The MAb productivity by the non
      immobilized cells obtained by dissolving collagen using a collagenase gradually
      decreased and returned to the original level in the batch culture using a fresh
      medium. This suggests that the direct contact of the cells or a very close
      distance between the cells has something to do with the enhancement of the MAb
      productivity, and the higher productivity is kept for a while in each cell after
      they are drawn apart.

PMID- 22358516
TI  - Simulation and dynamic optimisation of animal cell culture.
AB  - In animal cell culture, there are some 25 substrates that both have a significant
      effect on the culture performance and which can be measured with relative ease. A
      detailed dynamic simulation for such a culture has been produced and an
      optimisation policy that use this model to identify ideal media conditions has
      been developed. This paper describes an extension of that work to include the
      dynamic optimisation of cultures under fed-batch operation. Two different types
      of feeding policy were considered - in the first, discrete shots of feed were
      supplied, while in the second, feed was added continuously. Both policies offered
      significant improvements in the predicted productivity of the culture - up to 30%
      that of an experimentally "optimised"batch culture.

PMID- 22358517
TI  - Current good manufacturing practice in plant automation of biological production
      processes.
AB  - The production of biologicals is subject to strict governmental regulations.
      These are drawn up in current good manufacturing practices (cGMP), a.o. by the
      U.S. Food and Drug Administration. To implement cGMP in a production facility,
      plant automation becomes an essential tool. For this purpose Manufacturing
      Execution Systems (MES) have been developed that control all operations inside a
      production facility. The introduction of these recipe-driven control systems that
      follow ISA S88 standards for batch processes has made it possible to implement
      cGMP regulations in the control strategy of biological production processes. Next
      to this, an MES offers additional features such as stock management, planning and
      routing tools, process-dependent control, implementation of software sensors and
      predictive models, application of historical data and on-line statistical
      techniques for trend analysis and detection of instrumentation failures. This
      paper focuses on the development of new production strategies in which cGMP
      guidelines are an essential part.

PMID- 22358518
TI  - Development of a bioartificial liver employing xenogeneic hepatocytes.
AB  - Liver failure is a major cause of mortality. A bioartificial liver (BAL)
      employing isolated hepatocytes can potentially provide temporary support for
      liver failure patients. We have developed a bioartificial liver by entrapping
      hepatocytes in collagen loaded in the luminal side of a hollow fiber bioreactor.
      In the first phase of development, liver-specific metabolic activities of
      biosynthesis, biotransformation and conjugation were demonstrated. Subsequently
      anhepatic rabbits were used to show that rat hepatocytes continued to function
      after the BAL was linked to the test animal. For scale-up studies, a canine liver
      failure model was developed using D-galactosamine overdose. In order to secure a
      sufficient number of hepatocytes for large animal treatment, a collagenase
      perfusion protocol was established for harvesting porcine hepatocytes at high
      yield and viability. An instrumented bioreactor system, which included dissolved
      oxygen measurement, pH control, flow rate control, an oxygenator and two hollow
      fiber bioreactors in series, was used for these studies. An improved survival of
      dogs treated with the BAL was shown over the controls. In anticipated clinical
      applications, it is desirable to have the liver-specific activities in the BAL as
      high as possible. To that end, the possibility of employing hepatocyte spheroids
      was explored. These self-assembled spheroids formed from monolayer culture
      exhibited higher liver-specific functions and remained viable longer than
      hepatocytes in a monolayer. To ease the surface requirement for large-scale
      preparation of hepatocyte spheroids, we succeeded in inducing spheroid formation
      in stirred tank bioreactors for both rat and porcine hepatocytes. These spheroids
      formed in stirred tanks were shown to be morphologically and functionally
      indistinguishable from those formed from a monolayer. Collagen entrapment of
      these spheroids resulted in sustaining their liver-specific functions at higher
      levels even longer than those of spheroids maintained in suspension. For use in
      the BAL, a mixture of spheroids and dispersed hepatocytes was used to ensure a
      proper degree of collagen gel contraction. This mixture of spheroids and
      dispersed cells entrapped in the BAL was shown to sustain the high level of liver
      specific functions. The possibility of employing such a BAL for improved clinical
      performance warrants further investigations.

PMID- 22358519
TI  - Dialysis cultures with immobilized hybridoma cells for effective production of
      monoclonal antibodies.
AB  - An industrial scale reactor concept for continuous cultivation of immobilized
      animal cells (e.g. hybridoma cells) in a radial-flow fixed bed is presented,
      where low molecular weight metabolites are removed via dialysis membrane and high
      molecular products (e.g. monoclonal antibodies) are enriched. In a new "nutrient
      split" feeding strategy concentrated medium is fed directly to the fixed bed
      unit, whereas a buffer solution is used as dialysis fluid. This feeding strategy
      was investigated in a laboratory scale reactor with hybridoma cells for
      production of monoclonal antibodies. A steady state monoclonal antibody
      concentration of 478 mg l(-1) was reached, appr. 15 times more compared to the
      concentration reached in chemostat cultures with suspended cells. Glucose and
      glutamine were used up to 98%. The experiments were described successfully with a
      kinetic model for immobilized growing cells. Conclusions were drawn for scale-up
      and design of the large scale system. ABBREVIATIONS: c(Glc) - glucose
      concentration, mmol l(-1); c(Gln) - glutamine concentration, mmol l(-1); c(Amm) -
      ammonia concentration, mmol l(-1); c(Lac) - lactate concentration, mmol l(-1);
      c(MAb) - MAb concentration, mg l(-1); D - dilution rate, d(-1); D(i) - dilution
      rate in the inner chamber of the membrane dialysis reactor, d(-1); D(0) -
      dilution rate in the outer chamber of the membrane dialysis reactor, d(-1);
      q*(FB,Glc) - volume specific glucose uptake rate related to the fixed bed volume,
      mmol l(FB) (-1) h(-1); q*(FB,Gln) - volume specific glutamine uptake rate related
      to the fixed bed volume, mmol l(FB) (-1) h(-1).

PMID- 22358520
TI  - Effects of temperature shift on cell cycle, apoptosis and nucleotide pools in CHO
      cell batch cultues.
AB  - Temperature reduction in CHO cell batch culture may be beneficial in the
      production of recombinant protein and in maintenance of viability. The effects on
      cell cycle, apoptosis and nucleotide pools were studied in cultures initiated at
      37 degrees C and temperature shifted to 30  degrees C after 48 hours. In control
      cultures maintained at 37  degrees C, viable cells continued to proliferate until
      the termination of the culture, however, temperature reduction caused a rapid
      decrease in the percent of cells in S phase and accumulation of cells in G-1.
      This was accompanied by a concurrent reduction in U ratio (UTO/UDP-GNAc),
      previously shown to be a sensitive indicator of growth rate. Culture viability
      was extended following temperature shift, as a result of delayed onset of
      apoptosis, however, once initiated, the rate and manner of cell death was similar
      to that observed at 37  degrees C. All nucleotide pools were similarly degraded
      at the time of apoptotic cell death. Temperature reduction to 30  degrees C did
      not decrease the energy charge of the cells, however, the overall rate of
      metabolism was reduced. The latter may be sufficient to extend culture viability
      via a reduction in toxic metabolites and/or limitation of nutrient deprivation.
      However, the possibility remains that the benefits of temperature reduction in
      terms of both viability and productivity are more directly associated with
      cultures spending extended time in G-1.

PMID- 22358521
TI  - Establishing apoptosis resistant cell lines for improving protein productivity of
      cell culture.
AB  - The authors established apoptosis resistant COS-1, myeloma, hybridoma, and Friend
      leukemia cell lines by genetically engineering cells, aiming at more efficient
      protein production by cell culture. COS-1 cells, which are most widely used for
      eukariotic gene expression, were transfected with human bcl-2 gene. Both bcl-2
      and mock transfected COS-1 cells were cultured at low (0.2%) serum concentration
      for 9 days. The final viable cell number of the bcl-2 transfected cells was
      ninefold of that of the mock transfectants. Both bcl-2 and mock transfectants
      were further transfected with the vector pcDNA-lambda containing SV40 ori and
      immunoglobulin lambda gene for transiently expressing lambda protein. The bcl-2
      expressing COS-1 cells produced more lambda protein than the mock transfected COS
      1 cells after 4 days posttransfection.Mouse myeloma p3-X63-Ag.8.653 cells, which
      are widely used as the partner for preparing hybridoma, and hybridoma 2E3 cells
      were transfected with human bcl-2 gene. Both bcl-2 transfected myeloma and
      hybridoma survived longer than the corresponding original cells in batch culture.
      The bcl-2 transfected 2E3 cells survived 2 to 4 four days longer in culture,
      producing 1.5- to 4-fold amount of antibody in comparison with the mock
      transfectants.Coexpression of bag-1 with bcl-2 improved survival of hybridoma 2E3
      cells more than bcl-2 expression alone. The bag-1 and bcl-2 coexpressing cells
      produced more IgG than the the cells expressing bcl-2 alone.Apoptosis of Friend
      murine erythroleukemia(F-MEL) cells was suppressed with antisense c-jun
      expression. The antisense c-jun expressing cells survived 16 days at non-growth
      state.

PMID- 22358522
TI  - Death rate in a small air-lift loop reactor of vero cells grown on solid
      microcarriers and in macroporous microcarriers.
AB  - The death rate of Vero cells grown on Cytodex-3 microcarrierswas studied as a
      function of the gas flow rate in a smallair-lift loop reactor. The death rate may
      be described byfirst-order death-rate kinetics. The first-order death
      rateconstant as calculated from the decrease in viable cells, theincrease in dead
      cells and the increase in LDH activity islinear proportional to the gas flow
      rate, with a specifichypothetical killing volume in which all cells are killed
      ofabout 2.10(-3)m(3) liquid per m(3) of air bubbles.In addition, an experiment
      was conducted in the sameair-lift reactor with Vero cells grown inside porous
      Asahimicrocarriers. The specific hypothetical killing volumecalculated from this
      experiment has a value of 3.10(-4)m(3) liquid per m(3) of air bubbles, which
      shows thatthe porous microcarriers were at least in part able to protectthe cells
      against the detrimental hydrodynamic forcesgenerated by the bubbles.

PMID- 22358523
TI  - In vitro neurotoxicity of amyloid beta-peptide cross-linked by transglutaminase.
AB  - Transglutaminase catalyzes the intermolecular cross-linking of peptides between
      Gln and Lys residues, forming an epsilon-(gamma-glutamyl) lysine bond. Amyloid
      beta-peptide, a major constituent of the deposits in Alzheimer disease, contains
      Lys16, Lys28, and Gln15 which may act as substrates of transglutaminase.
      Transglutaminase treatment of amyloid beta-peptide (1-28) and amyloid beta
      peptide (1-40) yielded cross-linked oligomers. Transglutaminase-treated Abeta
      retarded neurite extension of PC12 cells, and rat cultured neurons of hippocampus
      and septum, brain areas severely affected by Alzheimer disease, and subsequently
      caused cell death, whereas the transglutaminase-untreated counterparts did not
      show harmful effects. The transglutaminase-catalyzed oligomers of amyloid beta
      peptide and their neurotoxicity may be involved in two characteristics in
      Alzheimer disease, neuronal degeneration and formation of the insoluble deposits.
      ABBREVIATIONS: AD - Alzheimer disease, Abeta - amyloid beta-peptide, DMEM -
      Dulbecco's modified Eagle's medium, DMEM/F-12-1:1 mixture of DMEM and Ham's F-12
      medium, FCS - fetal calf serum, HS - horse serum, PAGE - polyacrylamide gel
      electrophoresis, MTT - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide, NGF - nerve growth factor, TGase - transglutaminase.

PMID- 22358524
TI  - Apoptosis and its control in cell culture systems.
AB  - Apoptosis is a form of programmed cell death which exhibits highly distinctive
      morphology. Research activity in this area has increased substantially in recent
      years, primarily due to the realisation that disregulation of apoptosis is
      involved in the development of a number of pathological conditions, including
      cancer and AIDS. However, it is now clear that apoptosis also represents the
      dominant form of cell death during the culture of industrially important cell
      lines. This review focuses on the induction of apoptosis during industrial cell
      cultures as well as the effects of the apoptosis suppresser gene bcl-2 on cell
      survival in conditions relevant to bioreaction environments. We also present new
      data which demonstrates that bcl-2 can protect cells from apoptosis induced by
      oxygen deprivation, a finding which has important implications for large scale
      and intensive cultivation of cells. We also describe experiments which suggest
      that bcl-2 can reduce the specific nutrient consumption rate of cells.

PMID- 22358525
TI  - Basal medium development for serum-free culture: a historical perspective.
AB  - The evolution of basal synthetic formulations to support mammalian cell culture
      applications has been facilitated by the contributions of many investigators.
      Definition of minimally-required nutrient categories by Harry Eagle in the 1950's
      spawned an iterative process of continuous modification and refinement of the
      exogenous environment to cultivate new cell types and to support emerging
      applications of cultured mammalian cells. Key historical elements are traced,
      leading to the development of high potency, basal nutrient formulations capable
      of sustaining serum-free proliferation and biological production. Emerging
      techniques for alimentation of fed batch and continuous perfusion bioreactors,
      using partial nutrient concentrates deduced from spent medium analysis, can
      enhance medium utilization and bioreactor productivity.

PMID- 22358526
TI  - Factors limiting the commercial application of animal cells in culture.
AB  - The application of quality control and assurance procedures to the components of
      animal cell cultures has transformed what was an art to a viable industrial
      technology. This results in the successful large scale operation of such
      cultures. However it is clear that the cost of obtaining a license to produce
      materials from animal cells in culture severely impedes the movement of products
      into the market place. It is therefore necessary to examine in more detail the
      reasons for the reluctance of the regulatory authorities to issue product
      licences and in particular to appreciate the way ethical issues influence this
      process. This paper reviews these issues and indicates a way ahead.

PMID- 22358528
TI  - Assay systems for screening food components that have anti-proliferative and anti
      invasive activity to rat ascites hepatoma cells: In vitro and ex vivo effects of
      green tea extract.
AB  - We have developed in vitro and ex vivo assay systems for screening food
      components and natural substances that suppress the proliferation and/or invasion
      of a rat ascites hepatoma cell line of AH109A and have used them to study the
      effect of green tea extract. AH109A cells were found to penetrate underneath the
      monolayer of primary cultured mesothelial cells isolated from Donryu rat
      mesentery in the presence of 10% newborn bovine serum. Green tea extract
      inhibited this AH109A penetration in a dose dependent manner and also inhibited
      AH109A proliferation in vitro dose-dependently. Green tea tannin, the major
      polyphenolic substances in green tea extract, also inhibited the proliferation
      and invasion of AH109A in vitro in a dose dependent manner. When rat serum
      obtained 0.5 h after oral intubation of green tea extract was added to the
      culture media instead of newborn bovine serum at a concentration of 10%, the
      invasion of AH109A was significantly inhibited as compared to control rat serum
      (before green tea extract intubation); the inhibitory effect lasted for 1 h and
      disappeared 3 h after oral intubation of green tea extract, but those rat sera
      showed no inhibition of AH109A proliferation. These results suggest that green
      tea extract has an inhibitory effect on the invasion of AH109A both in vitro and
      ex vivo, but on the proliferation of AH109A only in vitro, and that these assay
      systems are effective for the screening of food components which inhibit tumor
      cell proliferation and invasion.

PMID- 22358527
TI  - Enhancing effects of food components on the production of interferon beta from
      animal cells suppressed by stress hormones.
AB  - In today's 'modern' society, no one can escape from the stresses of daily life.
      Stress stimulates the secretion of stress hormones (e.g. cortisol or
      noradrenaline) which generally suppress the immune response system, thus
      rendering the body vulnerable to infectious diseases and cancer. Therefore
      finding anti-stress food components, which diminish and/or inhibit the stress
      related suppression of the immune response system would be helpful in maintaining
      and promoting the health of the human population. Here we established a screening
      system for anti-stress substances using the cultured human cell line MG-63. The
      production of interferon-beta (IFN-beta) by MG-63 cells super-induced by Poly
      (I): Poly (C) was shown to decrease in a dose dependent manner upon the addition
      of 0.01-10 MUg/ml of cortisol or noradrenaline (NA). 1,2-Diacylglycerol (DG) was
      demonstrated to abrogate this suppression. Lipid from the fermented milk, kefir,
      also inhibited the influence of cortisol. Kefiran, a polysaccharide secreted from
      L. kafiranofasiens GKL-28 diminished the cortisol or NA influenced IFN-beta
      production. But phosphatidylcholine had no significant effect in this system.
      These results suggest that DG, lipids from kefir and kefiran may be equated as
      anti-stress food component.Abbreviations DG - diacylglycerol; IFN-beta -
      interferon-beta; NA - noradrenaline; PC - phosphatidylcholine; Poly (I):Poly (C) 
      polyinosinic polycytidylic acid.

PMID- 22358529
TI  - A small variance in the antigenicity but not function of recombinant beta
      lactoglobulin purified from the culture supernatant of transformed yeast cells.
AB  - We purified recombinant bovine beta-lactoglobulin (rbeta-LG) from the culture
      supernatant of transformed yeast and investigated whether rbeta-LG maintained the
      functional ability and antigenicity of native beta-LG. Immunostaining following
      gel electrophoresis and reversed-phase high-performance liquid chromatography
      confirmed that rbeta-LG was purified homogeneously. rbeta-LG showed almost the
      same retinol-binding ability as native beta-LG purified from bovine milk.
      However, affinities of two anti-beta-LG monoclonal antibodies (mAbs) to rbeta-LG
      were different from those to native beta-LG, although three other mAbs bound
      these two proteins equally. Since our panel of five mAbs has been previously
      shown to be able to detect structural changes occurring in beta-LG, this variance
      in antigenicity can be attributed to conformational differences between rbeta-LG
      and native beta-LG. Then, we studied which step in the production and
      purification procedure was responsible for altering the antigenicity of rbeta-LG.
      Bovine milk native beta-LG was added to several steps in this procedure and
      purified in the same manner as rbeta-LG. The results suggested that incubation in
      the yeast culture had adverse effects on maintaining the antigenicity of this
      recombinant protein. We conclude from these results that even if no difference
      between the native and recombinant proteins can be detected by functional
      analysis, some subtle conformational change which can be distinguished by mAbs
      may be incorporated into the recombinant protein during its production and
      ultimately cause a different immune reaction in vivo.Abbreviations beta-LG, beta
      lactoglobulin; rbeta-LG, recombinant beta-LG; PBS, phosphate-buffered saline; PBS
      Tween, PBS containing 0.05% Tween 20; ELISA, enzyme-linked immunosorbent assay.

PMID- 22358530
TI  - Role of a putative tyrosine-O-sulfate receptor in the targeting and/or
      intracellular transport of tyrosine-sulfated proteins.
AB  - By employing the affinity gel fraction technique, we have detected a 175 kDa
      tyrosine-O-sulfate (TyrS)-binding protein in sodium choleate extracts of the
      microsomal membrane fractions of bovine liver and pancreas, as well as canine
      liver and pancreas. Western blot analysis revealed the presence of the bovine
      liver TyrS-binding protein in complexes with tyrosine-sulfated proteins both in
      vivo and in vitro, suggesting the putative role of the former being the receptor
      for the latter. Using filter-grown Madin-Darby canine kidney (MDCK) cells as a
      model, it was demonstrated that the tyrosine-sulfated proteins synthesized were
      predominantly secreted into the apical medium. The results further indicate the
      production and differential polarized secretion of different sulfated forms of
      the two major secretory proteins produced by MDCK cells, fibronectin (FN) and an
      80 kDa glycoprotein (gp 80), with their tyrosine-sulfated forms being
      predominantly secreted from the apical surface. Treatment of filter-grown MDCK
      cells with glycosylation inhibitors, swainsonine and 1-deoxymannojirimycin,
      appeared to enhance the apical secretion of tyrosine-sulfated FN and gp 80. A
      similar 175 kDa membrane-bound 'TyrS receptor', cross-reactive toward antiserum
      against the canine liver TyrS receptor, was shown to be present in MDCK cells.
      Pulse-chase experiments revealed its presence in complexes with newly synthesized
      FN and gp 80. A hypothetical model for TyrS residues serving as an apical
      targeting signal during the biosynthetic transport of tyrosine-sulfated proteins,
      as mediated by the TyrS receptor, in MDCK cells is proposed.

PMID- 22358531
TI  - Building high affinity human antibodies by altering the glycosylation on the
      light chain variable region in N-acetylglucosamine-supplemented hybridoma
      cultures.
AB  - We attempted to improve antibody affinity by varying glycosylation on the light
      chain variable region. The human hybridoma line HB4C5 produces an antibody
      reactive to lung adenocarcinoma, which possess a N-glycosylated carbohydrate
      chain on the light chain hypervariable region. It has been shown that altering
      this carbohydrate structure can be accomplished by varying the level of N
      acetylglucosamine in glucose free medium, a change in the carbohydrate chain
      could be induced which resulted in modifying antigen binding. By culturing the
      cells in media containing more than 20 mM N-acetylglucosamine, cells produced
      antibody with 10 fold improved affinity as compared with antibody produced in 20
      mM glucose-containing medium. A newly induced light chain glycoform produced in
      the N-acetylglucosamine-containing medium was shown to be responsible for this
      antigen binding enhancement. Addition of glucose in the N-acetylglucosamine
      containing media led to decreased antibody affinity and slightly inhibited
      production of a new light chain in a dose-dependent manner. Combination of 20 mM
      N-acetylglucosamine and 0.5 mM glucose gave a higher antibody production without
      the decrease of the antigen binding. These results indicate that optimization of
      N-glycosylation on the light chain, which leads to higher antigen binding, can be
      accomplished by adjusting a ratio of glucose and N-acetylglucosamine in the
      culture medium.

PMID- 22358532
TI  - The immortalisation of rat hepatocytes by transfection with SV40 sequences.
AB  - Abbreviations EGTA - ethylene bis(oxyethylenenitrilo)-tetraacetic acid; F12 -
      Ham's F12; FBS - foetal bovine serum; HBSS - Hank's balanced salt solution; HDM -
      hormonally defined medium; HEPES - 4-(2-hydroxyethyl)-1-piperazine
      ethanesulphonic acid; NBS - new born calf serum; WME - Williams' medium E.

PMID- 22358533
TI  - Bovine oviductal epithelial cells: their cell culture and applications in studies
      for reproductive biology.
AB  - Epithelial cells of the mammalian oviduct play an important role in reproductive
      and developmental events that occur there. Oviductal epithelial cells from
      several mammalian species can be isolated and cultured in serum or serum-free
      medium in vitro and cell culture of bovine oviductal epithelial cells (BOEC) has
      been described by many investigators. Cultured BOEC show a wide variety of
      secretory activities and these secretory factors may influence early embryonic
      development or sperm function. Monolayer cultures of BOEC have been widely used
      for in vitro co-culture of bovine preimplantation embryos. The use of BOEC co
      culture systems has improved embryonic development in nearly all the studies
      conducted. In addition, interaction of bovine spermatozoa with BOEC, in a similar
      manner to that observed for spermatozoa in vivo, induced specific changes in
      sperm capacitation and consequently improved the fertilizing capacity of bovine
      spermatozoa in vitro. Thus co-culture systems with BOEC may not only offer an
      excellent model for studying the mechanisms of capacitation and acrosome reaction
      of bovine spermatozoa but also provide a useful tool for the improvement of
      embryo development in vitro.

PMID- 22358534
TI  - Functional characterization of human T cells immortalized by oncogene
      transfection.
AB  - We have succeeded in immortalizing human lymphocytes derived from the peripheral
      blood of a healthy donor and of an atopic patient, and from the lymph node of a
      cancer patient by oncogene transfection (Alam et al., 1996). All immortalized
      human lymphocytes were shown to be CD3+ and CD19-, indicating that these
      immortalized human lymphocytes were all T cells. We established 317, 154 and 692
      individual immortalized human T cell lines derived from the healthy donor, the
      atopic patient and the cancer patient, respectively. The ratios of CD4+ and CD8+
      subpopulations within the set containing immortalized T cells derived from the
      healthy donor were shown to be varied depending on the combinations of
      transfected oncogenes used. However, CD8+ cells were found to be the dominant
      subpopulation of immortalized T cells derived from the atopic patient and the
      cancer patient. These immortalized T cells showed different proliferative
      responses in the presence of exogenous human IL-2 depending on their origin, and
      was consistent with the surface expression of the IL-2 receptor. Furthermore, the
      cytokine secretion patterns of these immortalized T cells stimulated with mitogen
      were investigated. The results showed that the immortalized T cells from the
      healthy donor is able to secrete various kinds of cytokines such as IL-2, IL-10,
      beta-IFN and GM-CSF. However, immortalized T cells from the cancer patient was
      shown to only secrete IL-2 and GM-CSF. These results suggest that depending on
      the origin, the immortalized T cells came from different subsets or from cells in
      different activated states. Mixed lymphocytes reactions demonstrated that these
      immortalized T cells are able to proliferate in the presence of allogenic or
      xenogenic stimulator cells, suggesting that they maintain the ability to
      recognize specific antigens on the stimulator cells and can proliferate even
      after the immortalization. Furthermore, immortalized T cells derived from the
      healthy donor and the cancer patient strongly responded to K562 cells, suggesting
      that MHC-nonrestricted killer T cells were also immortalized.Abbreviations IL-2R 
      interleukin 2 receptor; MLR - mixed lymphocyte reaction.

PMID- 22358535
TI  - Evidence that phosphatidylcholine-specific phospholipase C is a key molecule
      mediating insulin-induced enhancement of gene expression from human
      cytomegalovirus promoter in CHO cells.
AB  - The signal transduction from insulin to its receptors and Ras has been
      extensively studied, while little has been reported beyond these steps. We found
      that the expression of human interleukin 6 gene under the control of immediate
      early gene promoter of human cytomegalovirus was enhanced by insulin sitmulation
      in Chinese hamster ovary cells. The induction effect of insulin was not
      significantly affected by inhibitors or activators of conventional protein kinase
      C, cAMP dependent protein kinase and phosphoinositide -3 kinase, however, pre
      incubation of the cells with D609, a specific inhibitors of phosphatidylcholine
      specific phospholipase C completely abolished the induction effect. These results
      clearly demonstrate that phosphatidylcholine-specific phospholipase C is a key
      molecule mediating insulin-induced enhancement of hIL-6 expression from the human
      cytomegalovirus promoter in Chinese hamster ovary cells and strongly suggest that
      it plays an important role in the insulin signaling pathways.Abbreviations CHO -
      Chinese hamster ovary; hCMV promoter - immediate early gene promoter of human
      cytomegalovirus; hIL-6 - human interleukin 6; PC-PLC-phosphatidylcholine-specific
      phospholipase C; PI-3 kinase - phosphoinositide 3 kinase; PKA - cAMP dependent
      protein kinase; PKC - protein kinase C.

PMID- 22358536
TI  - Induction of auto-logous human cytotoxic T lymphocytes (CTL) from peripheral
      blood against tumor cells.

PMID- 22358537
TI  - Culture of cells from two life stages of Schistosoma mansoni.
AB  - The ability to culture continuously proliferating cell lines of various organisms
      in vitro has provided numerous advantages in experimental approaches toward the
      understanding of basic biology and disease. Although in vitro approaches are
      common in many disciplines, this methodology has proven difficult to exploit in
      the study of helminthic parasites. A major cause of parasitic disease,
      particularly in tropical countries, is the trematode Schistosoma mansoni. We have
      developed in vitro techniques that allow the long term maintenance of cell
      cultures from two stages of the life cycle of this organism, associated with its
      mammalian and the molluscan hosts. We have developed quantitative assays of cell
      survival and proliferation in our culture systems, and obtained evidence for
      limited proliferation in vitro. Although the cultures we have achieved thus far
      are useful for many kinds of experiments in vitro, development of continuously
      proliferating cell lines remains our goal.

PMID- 22358538
TI  - Cell cultures derived from early zebrafish embryos differentiate in vitro into
      neurons and astrocytes.
AB  - The zebrafish is a polular nonmammalian model for studies of neural development.
      We have derived cell cultures, initiated from blastula-stage zebrafish embryos,
      that differentiate in vitro into neurons and astrocytes. Cultures were initiated
      in basal nutrient medium supplemented with bovine insulin, trout serum, trout
      embryo extract and fetal bovine serum. After two weeks in culture the cells
      exhibited extensive neurite outgrowth and possessed elevated levels of
      acetylcholinesterase enzyme activity. Ultrastructural analysis revealed that the
      neurites possessed microtubules, synaptic vessicles and areas exhibiting growth
      cone morphology. The cultures expressed proteins recognized by antibodies to the
      neuronal and astrocyte-specific markers, neurofilament and glial fibrillary
      acidic protein (GFAP). Poly-D-lysine substrate stimulated neurite outgrowth in
      the cultures and inhibited the growth of nonneuronal cells. Medium conditioned by
      the buffalo rat liver line, BRL, promoted the growth and survival of the cells in
      culture. Mitotically active cells were identified in cultures that had undergone
      extensive differentiation. The embryo cell cultures provide an in vitro system
      for investigations of biochemical parameters influencing zebrafish neuronal cell
      growth and differentiation.

PMID- 22358540
TI  - In remembrance of professor Murakami.

PMID- 22358539
TI  - Cell suicide in starving hybridoma culture: survival-signal effect of some amino
      acids.
AB  - Two mouse hybridoma cell lines cultured in different basal media withthe iron
      rich protein-free supplement were subjected to deliberatestarvation by
      inoculation into media diluted with saline to 50% or less.In the diluted media
      the growth was markedly suppressed and a largefraction of cells died by
      apoptosis. The cells could be rescued fromapoptotic death by individual additions
      of amino acids, such as glycine,L-alanine, L-serine, L-threonine, L-proline, L
      asparagine, L-glutamine,L-histidine, D-serine, beta-alanine or taurine. Amino
      acids withhydrophobic or charged side chains were without effect. The
      apoptosispreventing activity manifested itself even in extremely diluted
      media,down to 10% of the standard medium. The activity of L-alanine in
      theprotection of cells starving in 20% medium was shown also in
      semicontinuousculture. In the presence of 2 mM L-alanine the steady-state viable
      cell density more than doubled, with respect to control, andthe apoptotic index
      dropped from 37% in the control to 16%. It wasconcluded that the apoptosis
      preventing amino acids acted as signalmolecules, rather than nutrients, and that
      the signal had a character ofa survival factor. The specificity of present
      results, obtained with twodifferent hybridomas, supports our view (Franek and
      Chladkova-Sramkova, 1995) that the membranetransport macromolecules themselves
      may play the role of therecognition elements in a signal transduction pathway
      controlling thesurvival of hybridoma cells.

PMID- 22358541
TI  - R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not
      survival or bone-resorbing function of mature osteoclasts.
AB  - R848, also known as resiquimod, acts as a ligand for toll-like receptor 7 (TLR7)
      and activates immune cells. In this study, we examined the effects of R848 on
      differentiation, survival, and bone-resorbing function of osteoclasts. R848
      inhibited osteoclast differentiation of mouse bone marrow-derived macrophages
      (BMMs) and human peripheral blood-derived monocytes induced by receptor activator
      of NF-kappaB ligand in a dose-dependent manner. In addition, it inhibited mouse
      osteoclast differentiation induced in cocultures of bone marrow cells and
      osteoblasts in the presence of dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. However,
      R848 did not affect the survival or bone-resorbing activity of mouse mature
      osteoclasts. R848 also upregulated the mRNA expression levels of interleukin (IL)
      6, IL-12, interferon (IFN)-gamma, and inducible nitric oxide synthase in mouse
      BMMs expressing TLR7. IFN-beta was consistently expressed in the BMMs and
      addition of neutralizing antibodies against IFN-beta to the cultures partially
      recovered osteoclast differentiation inhibited by R848. These results suggest
      that R848 targets osteoclast precursors and inhibits their differentiation into
      osteoclasts via TLR7.

PMID- 22358542
TI  - Clinical efficacy and safety of intravenous itraconazole in the management of
      invasive candidiasis in patients of surgery and critical care.
AB  - Although itraconazole exhibits potent activity against Candida species, there
      have been few studies examining the use of intravenous itraconazole in the
      treatment of invasive candidiasis. A nationwide multicenter clinical study was
      conducted to evaluate the efficacy and safety of intravenous itraconazole in the
      management of invasive candidiasis, including non-albicans Candida species, in
      non-neutropenic patients undergoing surgery and critical care. Between September
      2007 and August 2009, patients with proven and presumed candidiasis were enrolled
      at 22 participating institutions. Patients with presumed candidiasis had a deep
      body temperature of 37.8 degrees C or higher and were positive for serum beta-D: 
      glucan or two or more colonization sites of Candida species. The main exclusion
      criterion was severe renal impairment (creatinine clearance <30 ml/min). The
      primary efficacy analysis was based on clinical and microbiological responses 5
      10 days after the end of treatment, assessed by an independent data review
      committee. Of the 60 patients enrolled, 49 were included in the modified
      intention-to-treat population; 31 patients received a definitive diagnosis and 18
      patients a presumed diagnosis. Intravenous itraconazole was used as first-line
      therapy to treat 39 patients and as second-line therapy for 10 patients. The
      isolated species included Candida albicans (25 strains with definitive diagnosis
      and 17 with presumed diagnosis) and non-albicans species (16 and 10,
      respectively). Treatment was successful in 61.5% patients (65.5% in first-line
      and 50.0% in second-line therapy); 60% of proven invasive candidiasis (IC)
      patients were judged as successful compared with 63.2% of presumed candidiasis
      patients. Eradication rate was 63.6% for C. albicans and 71.4% for C. glabrata.
      Adverse effects occurred in 9 of 60 patients (15.0%), commonly impaired liver
      function. The clinical efficacy and safety of intravenous itraconazole were
      suggested in the management of proven and presumed candidiasis including C.
      glabrata in non-neutropenic patients. The status of intravenous itraconazole in
      the Japanese guideline warrants reconsideration.

PMID- 22358543
TI  - Prevalence of methicillin-resistant Staphylococcus aureus based on culture and
      PCR in inpatients at a tertiary care center in Tokyo, Japan.
AB  - We investigated active screening for colonization with methicillin-resistant
      Staphylococcus aureus (MRSA) on admission and weekly follow-up surveillance after
      admission to a tertiary care center (TCC) between June 2007 and 31 December 2007.
      Eleven percent (30/267) of patients were found to be positive for MRSA by
      polymerase chain reaction (PCR) and/or culture on admission; 5% (12/267) became
      positive during the TCC stay. The major primary diagnoses in MRSA-positive
      patients were pneumonia and cerebrovascular diseases. Twenty-two (52%) of 42
      patients were found to be MRSA positive by both PCR and culture, compared with 19
      (45%) of 42 who were PCR positive and culture negative. These findings suggest
      that active surveillance with PCR is highly sensitive and useful for the
      detection of MRSA colonization. To our knowledge, this is the first report of
      active surveillance of MRSA by PCR and bacterial culture in critically ill
      inpatients in Japan.

PMID- 22358544
TI  - Letter to the editor.

PMID- 22358545
TI  - Isolation, culture and characterization of a primary fibroblast cell line from
      channel catfish.
AB  - A primary cell line (designated as CCf) derived from caudal fin tissue of channel
      catfish, Ictalurus punctatus, was developed using explant techniques. The cell
      line grew fastest in media supplied with FBS and channel catfish serum. The
      duplication time of the cell line under optimal conditions was ~56 h at a plating
      density of 1.1 * 10(5) cells/ml. The cell line has been propagated continuously
      for 25 passages (1:4 dilution per passage), cryopreserved, and recovered
      successfully at different passages. The cultured cells had fibroblastic
      morphology, and synthesized fibronectin and Type I and III collagens in the
      cytoplasm. The cell line maintained the normal diploid chromosome number (58) of
      channel catfish throughout the experiment. Nucleolus organizer regions were
      located on the short arms of a pair of medium-sized submetacentrics, which is
      typical for channel catfish. This study provides a method for acquiring a cell
      line from juvenile catfish without sacrifice, and is especially useful for early
      screening of valuable fishes.

PMID- 22358546
TI  - Cystine/cysteine metabolism in cultured Sf9 cells: influence of cell physiology
      on biosynthesis, amino acid uptake and growth.
AB  - Spodoptera frugiperda (Sf9) insect cells proliferate in a cystine-free medium,
      with the same growth rate, reaching the same final cell density, as in a cystine
      containing medium, provided that the inoculum is taken from a pre-culture
      sufficiently early, at 47-53 h. With an inoculum from a 103 h culture an extended
      lag phase accompanied by cell death was observed during the first 50 h of cystine
      free culture, even though the culture had been adapted to cystine-free conditions
      for 10 passages. Cystine-free cultures seeded with a 103 h inoculum had lower
      growth rates and reached lower final cell densities than corresponding cystine
      supplied cultures. Cysteine biosynthesis occurs from methionine via the beta
      cystathionine pathway. More methionine was consumed by the cells in cystine-free
      media, and cystathionine was secreted when methionine and cystine were supplied
      in excess. The data suggest that cysteine biosynthesis is up-regulated in
      proliferating cells but down-regulated when the cells enter the stationary
      phase.In cultures supplied with cystine (10-100 mg 1(-1)), the specific uptake
      rate and total consumption of cystine, as well as the uptake of glutamate,
      glutamine and glucose increased with increasing cystine concentrations. These
      results are interpreted in view of system x (c) (-) , a concentration dependent
      amino acid transporter. Similarly, the consumption of amino acids transported by
      system L (ile, leu, val, tyr) was enhanced in cystine-containing cultures, as
      compared to cystine-free cultures. Uptake of cystine, methionine and system L
      amino acids ceases abruptly in all cultures, even before growth ceased. The
      specific growth rate starts to decline early during the growth phase, but this
      growth behaviour could not be correlated to the depletion of nutrients. We
      therefore propose that the observed growth pattern is a result of
      (auto)regulatory events that control both proliferation and metabolism.

PMID- 22358547
TI  - Yield and activity of Autographa californica multicapsid nucleopolyhedrovirus and
      Phthorimaea operculella granulosis virus in cloned and uncloned cell lines of P.
      operculella.
AB  - Three selected uncloned Pop 2, Pop 3, Pop 4 and two cloned cell lines Pop cl1A
      and Pop cl2B were derived from the original cell line established from
      Phthorimaea operculella (ORS-Pop-93). Three new non-selected cell lines ORS-Pop
      94A, ORS-Pop-94B and ORS-Pop-95 were also established from embryos of the same
      insect. Differences in morphology, growth rate and polypeptide profile were
      determined between these cell lines. All the cell lines were susceptible to the
      Autographa californica nucleopolyhedrovirus (AcMNPV). The cloned cell lines
      produced higher levels of AcMNPV (TCID-50 and PIB) than the parental cells and at
      the same rate as the Sf9 reference cell line. Substantial amounts of viral DNA
      were synthesized in the clone Pop cl 2B after infection with the granulosis virus
      of the potato tuber moth P. operculella (PTMGV) and a complete multiplication was
      obtained in the ORS-Pop-95 cell line. The comparison between Pop cell lines which
      support limited or complete replication of certain baculoviruses can offer
      insights into some of the molecular barriers which restrict the host range of
      these viruses. These cell lines with variable susceptibility to baculoviruses
      could also be used for in vitro recombinations, increasing their virus host range
      to be used for the control of this pest.

PMID- 22358548
TI  - Spermine enhances IgM productivity of human-human hybridoma HB4C5 cells and human
      peripheral blood lymphocytes.
AB  - The polyamine spermine was assessed for enhancement of IgM production by human
      human hybridoma, HB4C5 cells, under serum-free conditions. IgM production of
      HB4C5 cells was stimulated approximately 6-fold by the addition of 7.3 mM of
      spermine. The facilitating effect was observed soon after inoculation. In spite
      of suppression of cell growth, the IgM production rate was accelerated for at
      least 5 days without medium change. Moreover, laser confocal microscopic analysis
      revealed that the IgM content inside HB4C5 cells was increased by spermine
      treatment. These findings suggest that spermine enhances specific IgM
      productivity of the hybridoma line. Spermine also facilitated IgM production by
      human peripheral blood lymphocytes under serum-free conditions. This result
      implies that spermine enhances immunoglobulin production of not only specific
      hybridoma lines, but also non-specific immunoglobulin producers. Immunoglobulin
      production stimulating activity of spermine was accelerated 2-fold by the
      addition of DNA whith a chain length of about 400-7000 base pairs (bp). However,
      degraded short-chain DNA fragments (less than 200 bp) did not facilitate the
      immunoglobulin production stimulating activity of spermine.

PMID- 22358549
TI  - Expansion of human autologous cytotoxic T lymphocytes on fixed target tumor
      cells.
AB  - Human tumor specific cytotoxic T lymphocytes (CTL) were expanded on formalin
      fixed autologous target tumor cells derived from glioblastoma multiforme. Growth
      response of the CTL restimulated with the fixed target cells was larger than
      those with live target cells. The results suggest that formalin-fixed tumor cells
      will be stable sources of tumor antigen for efficient autologous CTL expansion
      and be useful for adoptive immunotherapy of tumors.

PMID- 22358550
TI  - The enhancement of growth and differentiation of rat adrenal nerve cells by the
      addition of conditioned medium from human fibroblast cultures.
AB  - The growth of rat adrenal nerve cells was remarkably enhanced by supplementing
      the cultured medium from the human fibroblast cell line, Hs 68. Maximum specific
      growth rate and length of the neurites were observed as 0.076 (1/hr) and 0.026
      mm, respectively in 20% supplement of five day old medium. In adding more than
      20% of the cultured medium both cell and neurite growth was severely decreased.
      It was interesting that the cultured medium from Hs 68 cells could play a role in
      the extension of the neurites rather than in the growth of neurite cells. It was
      also found that molecules lower than 50,000 daltons in the conditioned medium
      could improve the growth of neurite bearing cells and the extension of the
      neurites than larger molecules. The efficacy of the proteins (<50,000 MW) was
      similar to that of human nerve growth factor and much better than that of basic
      fibroblast growth factor which was mainly secreted from human fibroblast cells.

PMID- 22358551
TI  - Long-term stable production of monocyte-colony inhibition factor (M-CIF) from CHO
      microcarrier perfusion cultures.
AB  - Monocyte-colony inhibition factor (M-CIF) was produced in microcarrier perfusion
      cultures from engineered Chinese hamster ovary (CHO) cells. Three and fifteen
      liter microcarrier perfusion bioreactors equipped with internal spin filters were
      operated for over two months. Approximately 60 L and 300 L of culture filtrate
      were harvested from the 3L and 15L microcarrier perfusion bioreactors
      respectively. During the perfusion operation, cell density reached 2-6 * 10(6)
      cells/ml. Importantly, stable expression of M-CIF from the CHO cells under non
      selection condition was maintained at a level of 4-10 mg/L. Specific productivity
      was maintained at 1.8-3.4 mg/billion cells/day. The ability of the recombinant
      CHO cells to migrate from microcarrier to microcarrier under our proprietary HGS
      CHO-3 medium greatly facilitated microcarrier culture scale-up and microcarrier
      replenishment. Future directions for microcarrier perfusion system scale-up and
      process development are highlighted.

PMID- 22358552
TI  - Descriptive parameter evaluation in mammalian cell culture.
AB  - Several methods exist for assessing population growth and protein productivity in
      mammalian cell culture. These methods were critically examined here, based on
      experiments with two hybridoma cell lines. It is shown that mammalian cell
      culture parameters must be evaluated on the same basis. In batch culture mode
      most data is obtained on a cumulative basis (protein product titre, substrate
      concentration, metabolic byproduct concentration). A simple numerical integration
      technique can be employed to convert cell concentration data to a cumulative
      basis (cell-hours). The hybridoma lines used in this study included a
      nutritionally non-fastidious line producing low levels of MAb and a nutritionally
      fastidious hybridoma with high productivity. In both cases the cell-hour approach
      was the most appropriate means of expressing the relationship between protein
      productivity and cell population dynamics. The cell-hour approach could be used
      as the basis for all metabolic population parameter evaluations. This method has
      the potential to be used successfully for both prediction and optimization
      purposes.

PMID- 22358553
TI  - Effect of culture temperature on a recombinant CHO cell line producing a C
      terminal alpha-amidating enzyme.
AB  - In order to seek an efficient method for producing a recombinant protein by using
      animal cell culture, we investigated various effects of the culture temperature
      on a recombinant CHO cell line (3u-1S), producing a C-terminal alpha-amidating
      enzyme (799BglIIalpha-AE) originating from Xenopus laevis. The results revealed
      that a low culture temperature (below 37  degrees C) led to the following
      phenomena: [1] inhibited cell growth, [2] enhanced cellular productivity of the
      recombinant protein, [3] maintained high cell viability, [4] suppressed medium
      consumption, and [5] suppressed release of impurities from the cells. These
      findings indicate that a quite simple method, the culture at low temperature,
      will contribute to the total improvement of the industrial process for the
      production of the recombinant protein, 799BglIIalpha-AE.

PMID- 22358554
TI  - Transport of osmoprotective compounds in hybridoma cells exposed to hyperosmotic
      stress.
AB  - Addition of osmoprotective compounds has a positive effect on growth and
      monoclonal antibody production in hyperosmotic hybridoma cell cultures. In order
      to better understand the processes involved in the osmoprotective response,
      uptake of the osmoprotective compounds glycine betaine, proline, sarcosine and
      glycine in mouse hybridoma cell line 6H11 during exposure to hyperosmotic stress
      was studied. Hyperosmotic stress (510 mOsmol/kg) was introduced through the
      addition of NaCl (100 mM) to the growth medium, and amino acid transport activity
      was measured immediately after transfer of the cells to the hyperosmotic medium.
      The osmoprotective capability of the four osmoprotectants tested was negatively
      affected if methylaminosobutyric acid (MeAiB), a specific substrate for amino
      acid transport system A, was simultaneously included in the hyperosmotic medium
      in equimolar amounts with one of the osmoprotective compounds. This was due to
      accumulation of MeAiB in the stressed cells, giving a significant reduction in
      the concentration of the osmoprotective compound inside the cells. Furthermore,
      addition of excess meAiB gave approx. 905 reduction in the initial rate of uptake
      of glycine betaine, while 40-50% reduction in the initial rate of uptake of
      proline, glycine and sarcosine. Similarly, addition of proline, glycine or
      sarcosine also gave a significant reduction in the initial rate of glycine
      betaine uptake. These results suggest that the four osmoprotective compounds
      share, at least in part, a common, MeAiB inhibitable carrier for transport into
      osmotically stressed hybridoma cells. This carrier is probably equal to amino
      acid transport system A.

PMID- 22358555
TI  - Development of a serum-free culture medium for the large scale production of
      recombinant protein from a Chinese hamster ovary cell line.
AB  - A serum-free medium, WCM5, has been developed for the large scale propagation of
      CHO (Chinese hamster ovary) cells which express recombinant protein using
      dihydrofolate reductase as a selectable marker. WCM5 was prepared by
      supplementing Iscoves medium without lecithin, albumin or transferrin with a
      number of components which were shown to benefit growth. WCM5 medium contained 5
      mg l(-1) human recombinant insulin (Nucellin) but was otherwise protein-free. CHO
      3D11(*) cells which had been engineered to express a humanised antibody,
      CAMPATH(*)-1H, were routinely grown using serum-containing medium. From a seeding
      density of 10(5) cells ml(-1), cells grown in static culture with serum reached a
      maximal cell density of 6.5*10(5) cells ml(-1) after 6 days in culture and
      produced a maximal antibody concentration of 69 mg l(-1) after 11 days in
      culture. CHO 3D11(*) cells grown with serum were washed in serum-free medium then
      cultured in WCM5 medium. Following a period of adaptation the cell growth and
      product yield was superior to that achieved with serum-containing medium. CHO
      cells producing CAMPATH-1H grown in an 8000 l stirred bioreactor seeded with
      2*10(5) cells ml(-1) reached a maximal viable cell density of 2.16*10(6) cells
      ml(-1) after 108 h in culture and a maximal antibody concentration of 131.1 mg l(
      1) after 122 h in culture.

PMID- 22358556
TI  - The optimization of serum-free medium for the production of the scu-PA by the
      addition of algal extracts.
AB  - The addition of 2.8 MUg/ml algal extracts enhanced both scu-PA production and
      cell growth in a serum-free medium, compared to a conventional serum-free medium
      for the cultivation of recombinant CHO cells. The growth rate and scu-PA
      production were relatively lower in the serum-free medium than 5% serum
      containing medium: however, specific scu-PA production rate was higher in the
      serum-free medium due to the long-term period of cultivation (3.66*10(-4) vs.
      2.48*10(-4) IU/cell/day). Overall scu-PA production rate was also greater in an
      enforced serum-free medium as 25,000 IU/day over 50 d of perfusion cultivation.
      The conversion ratio of scu-PA to tcu-PA was greatly reduced in the serum-free
      medium during perfusion cultivation (10% compared to 20% conversion in a serum
      containing medium).

PMID- 22358557
TI  - High cell density perfusion cultures of anchorage-dependent Vero cells in a depth
      filter perfusion system.
AB  - A depth filter perfusion system (DFPS) with polypropylene fibers had been
      demonstrated to support high density cultures of anchorage-independent hybridoma
      cells. The DFPS provides advantages of high surface-to-volume ratio of 450-600
      cm(2)/cm(3), low cost set-up, easy operation and scale-up. To test the
      feasibility of using DFPS for high density cultures of anchorage-dependent cells,
      Vero cells were cultivated in the DFPS. Gelatin coating on polypropylene fibers
      in the DFPS was necessary to promote cell attachment and growth. Dissolved oxygen
      (DO) concentrations could be controlled by sparging air into the reservoir vessel
      through a filter sparger. When DO concentration was controlled above 40% of air
      saturation in the DFPS with 40 MUm pore size, the maximum cell concentration as
      estimated on specific lactate production rate, was 3.81*10(7) cells/ml of the
      total reactor volume. This viable cell concentration is approximately 18 times
      higher than that obtained in a T-flask batch culture. Taken together, the results
      obtained here showed the potential of DFPS for high-density cultures of anchorage
      dependent cells.

PMID- 22358558
TI  - Automatic quantitation of cell colonies on petri dishes by computerized image
      analysis.
AB  - Clonogenic assay is one of the most sensitive assays, widely used to evaluate the
      effects of antineoplastic agentsin vitro. A computer program was developed on an
      IBAS 2.0 Image Analysis System for automated quantiation of cell colonies and
      clone area on Petri dishes. The sensitivity of the clonogenic assay can be
      greatly increased by evaluating the mean area of the clones. The program gives an
      objective, accurate and fast evaluation of large samples. It is simple to use and
      offers a high degree of flexibility. Special algorithms and techniques have been
      implemented for good quantitation of both connected and well-separated colonies
      and to reduce the background noise and the general error rate. The principles and
      solutions presented are applicable to any other image analysis system.

PMID- 22358559
TI  - The culture of rat myeloma and rat hybridoma cells in a protein-free medium.
AB  - Y0 is a rat x rat hybridoma cell line, which does not secrete immunoglobulin,
      produced using a fusion partner derived from the Y3 (Y3,Ag.1.2.3) rat myoloma
      cell line. Y0 and Y3 have both been widely used as fusion partners in the
      production of rat x rat hybridomas. Y0 has also been used in recombinant gene
      technology. Y0 cells grown in shake flask culture, using RPMI 1640 medium with
      4mM l-glutamine and 5% foetal bovine serum, reached a maximal cell density of
      1.5*10(6) cells ml(-1) with 86% viability. Y0 cells which has been adapted to
      grow in ABC protein-free medium reached a maximal density, in shake flask
      culture, of 8.75*10(5) cells ml(-1) with 79% viability. An improved protein-free
      medium, designated W38 medium, was developed. In shake flask culture, W38 medium
      supported Y0 cell growth to a density of 2.02*10(6) cells ml(-1) with 96%
      viability. Two Y3 hybridomas, YID 13.9.4 cells and SAM 618 cells were adapted to
      growth in W38 medium. For both hybridomas, cell growth and product yield in shake
      flask culture using W38 medium was superior to that obtained with serum
      containing RPMI 1640 medium.

PMID- 22358560
TI  - Adaptation of cholesterol-requiring NS0 mouse myeloma cells to high density
      growth in a fully defined protein-free and cholesterol-free culture medium.
AB  - NS0 has been used as a fusion partner for the production of hybridomas and has
      more recently been engineered to produce recombinant protein. A protein-free
      culture medium, designated W38 medium, has previously been developed which
      supported high density growth of rat myeloma and hybridoma cell lines. NS0 cells
      failed to grow in W38 medium and in a number of protein-free culture media which
      support the growth of other myeloma cell lines. NS0 cells are derived from the NS
      1 cell line, which is known to require exogencus cholesterol. It was found that
      NS0 cells grew in W38 medium supplemented with phosphatidylcholine, cholesterol,
      and albumin and that NS0 were auxotrophic for cholesterol. Protein-free growth of
      NS0 cells was achieved by using beta-cyclodextrin to replace albumin as a lipid
      carrier. The maximal cell density reached in this protein-free medium was in
      excess of 1.5*10(6) cell ml(-1). The lipid supplements in the medium precipitated
      after a few days storage at +4 degrees C. In order to overcome this problem a
      protocol was developed which allowed NS0 cells to be adapted to cholesterol
      independent growth in W38 medium. NS0.CF (cholesterol-independent NS0 cells) were
      cultured continuously in W38 medium for several months. In shake flask culture a
      cell density of 2.4*10(6) cells ml(-1) was achieved in W38 medium compared with
      1.41*10(6) cells ml(-1) in RPMI 1640 medium containing 10% foetal bovine serum.
      NS0.CF cells readily grew in a 1 litre stirred bioreactor using W38 medium
      supplemented with Pluronic F68 reaching a density of 3.24*10(6) cells ml(-1).
      NS0.CF were cloned protein-free by limiting dilution in W38 medium, giving
      colonies in wells that were seeded at an average density of 0.32 cells per 200
      MUl. This study has demonstrated for the first time the growth of a cholesterol
      requiring mouse myeloma cell line in a completely defined protein-free medium and
      its subsequent adaptation to cholesterol-independence.

PMID- 22358561
TI  - Cell substrates and world health.

PMID- 22358562
TI  - Batch production and growth kinetics of hybridomas.
AB  - Batch cultures of mouse-mouse hybridoma cell lines were carried out and their
      growth and production kinetics investigated. Three main cell specific production
      patterns (expressed as pg IgG/cell x hour) were found, which can be used as a
      classification system for hybridoma cell lines (groups I-III). Cells showing the
      highest IgG-production at the beginning of the batch culture (during the lag and
      the onset of the log-phase) were classified as either group I and II. The
      difference was that cell lines of group II showed a second high cell specific
      production at the onset of the stationary and death phases. Cell lines of group
      III had a quite constant production of antibodies during their growth; but IgG
      secretion completely stopped after the beginning of the stationary phase. The
      implications of these three production patterns on the design of a production
      process are discussed.

PMID- 22358563
TI  - Subculture of rabbit articular chondrocytes within a collagen gel: growth and
      analysis of differentiation.
AB  - Primary cultures of rabbit articular chondrocytes have been subcultured within
      three-dimensional (3D) collagen gels. Under these conditions, the cells remained
      viable and divided, but with a lower proliferation rate than that observed in
      control monolayer cultures. Flow cytometric analysis of progression of the cells
      into the cell cycle has confirmed and extended these findings. Also the cellular
      volume was decreased in 3D-culture, being in the same range as thein vivo size of
      cartilage cells. Specific staining for proteoglycans and type II collagen
      immunolocalization on sections of gels showed the expression of differentiated
      phenotypes and revealed the accumulation of these matrix components in the
      immediate surroundings of the cells. The use of Ultroser G (a serum substitute)
      improved the conditions for 3D- culture of rabbit articular chondrocytes.

PMID- 22358564
TI  - CG Dinucleotides of class II MHC genes are mutation hot-spots.
AB  - DNA methylation of human class II genes of the Major Histocompatibility Complex
      (MHC) was correlated with gene expression and methyl-related CG -> TG and CG ->
      CA changes. It was found that cytosine methylation of the CG dinucleotides of MHC
      class II genes should be involved in generating a fraction of nucleotide
      polymorphism, rather than in controlling transcription.

PMID- 22358565
TI  - Cytotoxicity of D-penicillamine in association with several heavy metals against
      cultured rabbit articular chondrocytes.
AB  - The potentiation or antagonistic effects of Cu, Hg, Pb and Cd salts in the
      presence of a long-acting anti-rheumatic drug, D-penicillamine (D.P.) were
      studied on cultured chondrocytes. CuSO(4) (10(-4)M), HgCl(2) (10(-5)M),
      Pb(CH(3)COO)(2) (10(-3)M) and D.P. (10(-3)M) when used alone caused a small
      decrease in cell proliferation. The addition of D.P. with Cu, Hg or Pb salts
      resulted in a marked increase in the extent of growth inhibition. In contrast,
      CdCl(2) (10(-5)M) produced an important growth inhibitory effect, and D.P.
      antagonized CdCl(2) action. The CuSO(4) D.P. toxicity was probably due to
      production of H(2)O(2) in situ. To verify this hypothesis, catalase, responsible
      for H(2)O(2) metabolism was used, and was found to partially reverse the
      inhibitory effect of CuSO(4)-D.P.

PMID- 22358566
TI  - Variation of amino acid concentrations in the medium of HU beta-IFN and HU IL-2
      producing cell lines.
AB  - There are different requirements for the nutrient medium of various mammalian
      cell lines. We have determined the behaviour of the amino acid concentrations in
      the medium of two growing cell lines used for producing human interleukin 2 and
      human interferon beta constitutively. The experiments are based on a fermentation
      process with a bubble free cell culture aeration system with porous moving
      membranes, which allows production of high cell densities without foaming. We
      found interesting alterations in which the actual amino acid ratios are able to
      trigger consumption and production of a particular component depending on the
      supply of other possible replacements. Such data indicate the complicated
      biochemical network of synthesis, conversion and transport phenomena. Finally, we
      demonstrated the influence of product synthesis upon the amino acid requirements
      using as an example transformed hu IL-2- and hu beta-IFN-producing mouse L-cells.

PMID- 22358567
TI  - Establishment of Namalva cell lines which grow continuously in glutamine-free
      medium.
AB  - Glutamine has been shown to be a preferred energy source for some established
      cell lines and cancer cells in culture (Kovacevic, 1971; Kovacevic, 1972;
      Lavietes, 1974). Empirically, glutamine is the most abundant amino acid in most
      of the culture media developed. The major end product of glutamine metabolism is
      ammonia. Ammonia build up is one of the limiting factors in the proliferation of
      mammalian cells in higher density culture and is directly related to the initial
      glutamine concentration. The susceptibility of glutamine to thermodecomposition
      prevents the heat sterilization of glutamine-enriched media and this
      significantly increases the cost of medium preparation at the industrial scale.
      In an attempt to overcome these drawbacks, a population of Namalva cells capable
      of growing in glutamine-free media was established. The adapted cells were found
      to contain a higher level of glutamine synthetase activity which enable them to
      synthesize sufficient amounts of glutamine for their growth.

PMID- 22358568
TI  - Egg yolk lipoprotein, a new supplement for the growth of mammalian cells in serum
      free medium : Egg yolk lipoprotein for serum-free growth of cells.
AB  - Egg yolk lipoprotein promoted growth of a wide variety of mammalian cell lines,
      including plasma-cytomas and epithelial cell lines, in serum-free medium. The
      lipoprotein was active for cell growth when used with insulin, transferrin,
      ethanolamine and selenite. The most active lipoprotein fraction (YLP-pI7.5) was
      purified to give a single peak by chromatofocusing and gel filtration, and was
      homogeneous on a 0.35% agarose gel electrophoretogram. The lipoprotein was
      characterised as a very low density lipoprotein with a protein content of only
      1.3%. This lipoprotein had an optimal concentration of 300 MUg/ml (4 MUg
      protein/ml). It was easily separable from proteinous molecules secreted into the
      serum-free medium by the cells, since it floated on the surface of the medium
      after addition of ammonium sulfate, to precipitate protein, and centrifugation.
      An associated structure of lipid and protein seemed to be still necessary for the
      lipoprotein to exhibit a growth promoting activity.

PMID- 22358569
TI  - High cell density perfusion culture of hybridoma cells recycling high molecular
      weight components.
AB  - We have developed a high cell density and high product concentration culture
      system recycling high molecular weight components. The production of monoclonal
      antibodies in high concentration was performed by this culture system with mouse
      human hybridoma H2 and V6 cells in serum-free defined media.The concentration of
      IgG after 48 days culture of H2 cells in ITES-eRDF reached 2 mg/ml and the purity
      of IgG in culture fluid was 61%. In addition, high molecular weight components in
      serum-free media, such as transferrin or BSA, could be reduced to 5% of the
      original concentration.

PMID- 22358570
TI  - Anin vitro model for the biological evaluation of dental materials using human
      periodontal ligament cells.
AB  - Anin vitro system is described which uses human diploid cells derived from the
      periodontal ligament. It simulates the clinical situation and is suitable for
      rapid cytotoxicity screening of dental materials. It can also be adapted to study
      various factors influencing biocompatibility.

PMID- 22358571
TI  - To the editor.

PMID- 22358572
TI  - Evolution of highly repeated DNA within the genusTriturus (Amphibia, Urodela).
AB  - Highly repeated DNA is a main feature of urodele amphibian genomes. InTriturus
      this class of DNA consists of several sequence families differently arranged at
      both the molecular and the chromosomal level, showing varying degrees of
      conservation across species. Present data on highly repeated DNA inTriturus are
      here summarized and discussed with regard to the evolution and possible
      functional role of these sequences.

PMID- 22358573
TI  - Genomic organization of ribosomal DNA and related sequences inTriturus.
AB  - The ribosomal RNA genes ofTriturus vulgaris meridionalis are clustered at
      variable and often multiple chromosomal loci. The rDNA repeats exhibit only a
      limited and discrete length heterogeneity which is accounted for by the non
      transcribed spacer (NTS). Interestingly, sequences homologous to the NTS are
      clustered outside the ribosomal loci. Clones containing such 'non ribosomal
      sequences' have been isolated from a genomic library ofT. v. meridionalis and
      analyzed by restriction mapping. These sequences appear to consist mostly of
      repetitive Bam HI fragments ranging from 500 bp to 1000 bp. The Bam HI fragments
      are internally repetitious and highly homologous to each other.

PMID- 22358575
TI  - High density culture of mouse-human hybridoma cells using a perfusion culture
      apparatus with multi-settling zones to separate cells from the culture medium.
AB  - Mouse-human hybridoma X87X cells were cultivated using a novel perfusion culture
      apparatus provided with three-settling zones to separate the cells from the
      culture medium by gravitational settling. The maximum viable cell density in a
      serum-free culture medium attained 3.0*10(7) cells/ml, when the specific
      perfusion rate was set to 2.3 vol day(-1), and monoclonal antibody was
      continuously produced. These results were almost the same as those in the
      perfusion culture vessel with one settling zone and revealed that the process
      with a plurality of settling zones is a promising one for scale-up of a
      gravitation type of perfusion culture vessel.

PMID- 22358576
TI  - SSGF-I, a potent growth-promoting substance for mammalian cells from swine serum.
AB  - A small amount of swine serum markedly stimulated cell growth for high
      productivity subclones derived from a mouse human-human heterohybridoma, N12
      16.63, secreting an anti-tetanus toxoid human monoclonal antibody in a
      polyethylene glycol (PEG)-containing serum-free medium, PEG-86-1. A growth
      promoting substance, SSGF-I, was isolated from the serum by ammonium sulfate
      fractionation, Cibacron blue F3A-G affinity chromatography, DEAE-agarose ion
      exchange chromatography, and gel filtrations on Trisacryl GF 2000 and Sephacryl S
      300. SSGF-I was characterized as a low density lipoprotein (LDL) of swine serum
      by its physico-chemical properties. It promoted cell growth synergistically with
      PEG and its optimum concentration was 1 to 100MUg/ml. Human LDL was less active,
      and human or swine high density lipoprotein (HDL) and very low density
      lipoprotein (VLDL) were inactive. Based on these results, we propose an improved
      serum-free medium, PEG-86-3, which contains all the ingredients of PEG-86-1 and
      10MUg/ml SSGF-I. This medium is useful for not only high productivity
      heterohybridomas but also for a variety of lymphoid cell lines.

PMID- 22358577
TI  - The effects of ionizing radiation on the glycosaminoglycan synthesis in embryonic
      cartilage in vitro.
AB  - The effects of ionizing radiation on the glycosaminoglycan synthesis of
      cartilaginous tibiae of 6.5 day old chick embryos have been studied in vitro over
      a 3 day period. As a parameter for the glycosaminoglycan synthesis, the
      incorporation of (3)H-glucosamine is evaluated by liquid scintillation counting.
      A radiation induced inhibition ranging from 6% at 20 Gy to 68% at 200 Gy is
      observed. Light microscopical autoradiographs reveal that the secretion of the
      newly synthesized glycosaminoglycans is not affected significantly by ionizing
      radiation up to 150 Gy. Electron microscopical pictures confirm this observation
      and show that the chondrocytes in the irradiated tibiae remain viable. At 200 Gy
      most cells are necrotic. The results indicate that the radiation effects on the
      synthesis of the extracellular matrix components are determined by the damage of
      the RNA transcription.

PMID- 22358578
TI  - Flow cytometric assessment of cell viability: a multifaceted analysis.
AB  - Flow cytometry offers the possibility to simultaneously analyze, on a cell by
      cell basis, different parameters related to cell viability i.e. cell size,
      morphology and incorporation of dyes. Different types of analysis: light
      absorption of unstained/stained cells, forward angle light scattering (FALS),
      right angle light scattering (RALS) or both, cell fluorescence based on dye
      retention or dye exclusion (due to erythrosin B, ethidium bromide, fluorescein
      diacetate, rhodamine 123) were tested and compared, with the classical Trypan
      blue exclusion test, for their effectiveness in the determination of cell
      viability. Two types of cells in monolayer cultures (L929, SIRC) and a freshly
      isolated suspension of mouse splenocytes were used. For each dye, the optimal
      dose, incubation time and conditions for analysis were determined. Viability
      indications by different techniques for the three type of cell line and their
      reliability as compared with Trypan blue were analyzed.

PMID- 22358579
TI  - Establishment of cell lines from serial samples from two patients with lung
      tumours before and after chemotherapy.
AB  - Six cell lines were derived from pleural effusions of two lung cancer patients
      and established in vitro in our laboratory. Cell line AE1 was obtained from a
      small cell lung cancer (SCLC) before the patient had received any chemotherapy;
      the other lines (AE2 and AE3) were established from tumour recurrences in the
      same patient after therapy. Cell lines DG1 and DG2 were derived from specimens of
      an untreated non-small cell lung cancer (NSCLC), while cell line DG3 originated
      from pleural effusions recurring in the same patient after therapy. The results
      of the present study show that: (a) the SCLC lines AE1, AE2 and AE3 are
      heterogeneous in their biological characteristics and in their chemosensitivity
      patterns. In particular lines AE2 and AE3 are less responsive to cis-Platinum
      (DDP) and Adriamycin (ADM) than line AE1, so that they may reflect resistant
      subpopulations existing within the original tumour, selected following therapy
      with these drugs. In contrast, however, line AE1 proved more resistant to Vepesid
      (VP16) than lines AE2 and AE3. (b) The three NSCLC lines are similar in various
      biological features as well as in their chemosensitivity to DDP and Vinblastine
      (VBL).

PMID- 22358580
TI  - Generation of lymphokine activated killer cells in a new high density dialyzing
      culture apparatus.
AB  - In order to establish an efficient culture system for the generation of
      lymphokine activated killer (LAK) cells, we have developed a new device which is
      essentially based on a continuous dialyzing culture vessel. LAK cells grown in
      such a system showed higher cytotoxicity than those grown under conventional
      culture conditions. By using this new apparatus with continuous regulation of
      infused interleukin 2, nutritional medium, and pO(2) and pCO(2), yields of
      2*10(7) cells/ml were achieved and maintained for more than 21 days. These cells
      also showed a significant increase of LAK activity on a per cell basis.

PMID- 22358581
TI  - Evaluation of NK-to-target cell binding and evidence for T cell conjugates by
      flow cytometry.
AB  - A flow cytometric methodology was set up to assess the binding capability of
      peripheral blood NK and T cells to the K562 tumor cell line. Differential side
      scatter characteristics between effectors and targets were used to analyze
      conjugated and unconjugated cells. The previous labeling of NK and T cells with
      anti-Leu 11c and anti-Leu 4 monoclonal antibodies, allowed the distinction
      between unconjugated non-fluorescent and conjugated fluorescent targets and the
      percentual evaluation of bound anti-Leu 11c(+) and anti-Leu 4(+) cells.

PMID- 22358582
TI  - Stimulation of monoclonal antibody production by human-human hybridoma cells with
      an elevated concentration of potassium or sodium phosphate in serum-free medium.
AB  - Potassium or sodium phosphate was found to stimulate the production of human
      monoclonal antibody by human-human hybridoma HB4C5. The addition of 15 mM Na
      phosphate (pH 7.4) into serum-free culture medium increased the antibody
      production up to 4-fold, when seeded at cell density of 1*10(5) cells/ml in
      dishes. At the higher cell density of 5*10(5) cells/ml, K-phosphate was more
      effective than Na-phosphate, at the same concentration. In large-scale continuous
      culture, the addition of 10 mM Na-phosphate into serum-free culture medium
      stimulated antibody production by HB4C5 cells 6-fold.

PMID- 22358583
TI  - Meeting report.

PMID- 22358584
TI  - SV40 Large T antigen mutant data base.

PMID- 22358585
TI  - Prospective multicenter study of visual outcomes following three different
      treatments for macular edema associated with branch retinal vein occlusion: a
      study by the Japanese BRVO study group.
AB  - PURPOSE: To evaluate the visual outcomes of three different treatments for
      macular edema associated with a branch retinal vein occlusion. METHODS: A 1-year,
      non-randomized study was conducted at 21 ophthalmological institutes in Japan.
      All of the patients received one of three treatments: medication per-oral (PO),
      photocoagulation (PC) or pars plana vitrectomy (PPV). Retinal hemorrhage that was
      lower than that shown in reference photographs was considered an inclusion
      criteria. RESULTS: Ninety-eight patients were studied. Twenty-six (26.5%)
      patients were in the PO, 37 (37.8%) in the PC and 35 (35.7%) in the PPV group.
      The mean best-corrected visual acuity (BCVA) improved significantly after 1 year
      in all groups (P < 0.001). There was no significant difference among those groups
      in the degree of the BCVA improvement. However, the BCVA in the PPV group
      improved significantly at 6 months, significantly earlier than in the other two
      groups. The BCVA at entry in the PPV group was significantly worst among patients
      whose eyes had a BCVA of >= 0.7 at 1 year (P < 0.05). CONCLUSIONS: PPV had a
      slight advantage over PC and PO, although the improvement to the BCVA did not
      differ significantly following any of the three treatments.

PMID- 22358586
TI  - Punctal plugs for treatment of post-LASIK dry eye.
AB  - PURPOSE: To evaluate the efficacy of punctal plugs for patients with post-LASIK
      dry eye. MATERIALS AND METHODS: A prospective study was conducted on 25 eyes of
      18 patients who underwent LASIK. All eyes fulfilled the Japanese dry-eye criteria
      and had not responded to conventional treatment with artificial tears by 1 month
      postsurgery. They were randomly divided into a plug and a non-plug group. Punctal
      plugs were inserted into the superior and inferior puncta in the plug group after
      the 1-month examination. Uncorrected and best corrected visual acuity (UCVA,
      BCVA), refraction, functional visual acuity (FVA) after 10 s eye opening (FVA
      10), surface regularity index (SRI) after 10 s eye opening (SRI 10), corneal
      sensitivity, Schirmer test, fluorescein staining (FS), tear break-up time (TBUT),
      and symptoms were compared between the groups 1 and 3 months postsurgery. Changes
      in these data from 1 to 3 months were also compared between the groups. RESULTS:
      The values in SRI 10, FS, and TBUT were significantly better in the plug group at
      3 months. Changes in the values of UCVA, FVA 10, FS, TBUT, and symptoms between 1
      and 3 months improved significantly in the plug group compared with the non-plug
      group. CONCLUSION: Our results suggest that punctal occlusion for both puncta is
      effective for patients with post-LASIK dry eye that cannot be controlled by
      artificial tears alone. Punctal plugs can improve not only the symptoms and tear
      function, but also the quality of vision, for example FVA.

PMID- 22358588
TI  - Editorial.

PMID- 22358589
TI  - Japanese association for animal cell technology.

PMID- 22358587
TI  - Survey of microphthalmia in Japan.
AB  - PURPOSE: To report the current status of patients with microphthalmia based on a
      cross-sectional survey of patient hospital visits. METHODS: A questionnaire was
      sent to the departments of ophthalmology in 1,151 major Japanese hospitals to
      survey the following: the number of patients with microphthalmia who visited the
      outpatient clinics between January 2008 and December 2009; gender; age; family
      history; associated ocular anomalies; complications and systemic diseases;
      surgical treatment; vision and management. A retrospective quantitative registry
      of 1,254 microphthalmic eyes (851 patients) from 454 hospitals (39.4%) was
      compiled. RESULTS: Of the patients for whom data were available, 50% ranged in
      age from 0 to 9 years. The major ocular findings were nanophthalmos, coloboma,
      and vitreoretinal malformations. Ocular complications frequently developed,
      including cataracts, glaucoma, and retinal detachment. Surgery was performed in
      21.4% of all cases, and systemic diseases were present in 31% of all cases. The
      vision associated with microphthalmia exceeded 0.1 in about 30% of the eyes.
      Glasses and low vision aids were used by 21.6% of patients. CONCLUSIONS: Patients
      with microphthalmia often have ocular and systemic anomalies. Early assessment
      and preservation of vision and long-term complication management are needed.

PMID- 22358590
TI  - The third annual meeting of the Japanese society for alternatives to animal
      experiments (JSAAE) held at Yokohama City University, Yokohama, Japan on October
      19-20, 1989.

PMID- 22358591
TI  - Insect cell physiology.

PMID- 22358592
TI  - A new astrocytic cell line which is able to induce a blood-brain barrier property
      in cultured brain capillary endothelial cells.
AB  - Astrocytes, a member of the glial cell family in the central nervous system, are
      assumed to play a crucial role in the formation of the blood-brain barrier (BBB)
      in vertebrates. It was shown that astrocytes induce BBB-properties in brain
      capillary endothelial cells (BCEC) in vitro. We now established an astroglial
      cell line of non-tumoral origin. The cloned cell line (A7) shows a highly
      increased proliferation rate and expresses the astrocytic marker glial fibrillary
      acidic protein. Furthermore, the clone A7 expresses S-100-protein and vimentin,
      which are also expressed by primary cultured astrocytes. This cell line therefore
      shows general astrocytic features. In addition, we were able to show that A7
      cells re-induce the BBB-related marker enzyme alkaline phosphatase in BCEC, when
      these two cell types are co-cultured. Thus we have a cell line which can be
      readily cultured in large quantities, shows common astrocyte properties and is
      able to influence BCEC with respect to a BBB-related feature.

PMID- 22358594
TI  - Effects of an internal transcription unit and its orientation on retrovirus titre
      and expression.
AB  - Using the retroviral vector pMsp, constructs were produced with different coding
      sequences under the control of the Herpes simplex virus type 1 (HSV) thymidine
      kinase (tk) promoter, with the internal coding sequence in the same or reverse
      orientations with respect to long terminal repeat (LTR)-driven transcription and
      with or without an internal tk polyadenylation (polyA) signal. Following
      introduction of these constructs into ecotropic or amphotropic packaging cell
      lines by transfection or infection, it was found that, most consistently, those
      constructs in which the internal coding sequence/polyA signal component was
      inserted in the same orientation as LTR-driven transcription produced lower
      titres of virus than those in which this component was inserted in the reverse
      orientation. Also, in a construct containing a coding sequence in the same
      orientation as LTR-driven transcription, but lacking an internal polyA signal,
      virus titre was much greater than in the corresponding construct possessing the
      internal polyA signal. Additionally, although functional assays have previously
      demonstrated expression of the inserted sequences, transcription from the
      internal tk promoter was inefficient in all these constructs.

PMID- 22358593
TI  - On-line immunoanalysis of monoclonal antibodies during a continuous culture of
      hybridoma cells.
AB  - The monoclonal-antibody production of an immobilized hybridoma cell line
      cultivated in a fluidized-bed reactor was monitored on-line for nearly 900 h. The
      monoclonal antibody concentration was determined by an immuno affinity
      chromatography method (ABICAP). Antibodies directed against the product, e.g.
      IgG, were immobilized on a micro-porous gel and packed in small columns. After
      all IgG present in the sample was bound to the immobilized antibodies, unbound
      proteins were removed by rinsing the column. Elution of the bound antibodies
      followed and the antibodies were determined by fluorescence. The analytical
      procedure was automated with a robotic device to enable on-line measurements. The
      correlation between the on-line determined data and antibody concentrations
      measured by HPLC was linear.A sampling system was constructed, which was based on
      a pneumatically actuated in-line membrane valve integrated into the circulation
      loop of the reactor. Separation of the cells from the sample stream was achieved
      by a depth filter made of glass-fibre, situated outside the reactor. Rapid
      obstruction of the filter by cells or cell debris and contamination of the sample
      system was avoided by intermittent rinsing of the sample system with a chemical
      solution. The intermittent rinsing of the filter, which had a surface of 4.8
      cm(2), resulted in an operational capacity of up to 40 samples (1.0 l total
      sample volume). Both the sampling system and the analytical device functioned
      without failure during this long-term culture.The culture temperature was varied
      between 34 and 40  degrees C. Raising the temperature from 34 up to 37  degrees C
      resulted in a simultaneous increase of growth and specific antibody production
      rate. Specific metabolic rates of glucose, lactate, glutamine and ammonium stayed
      constant in this temperature range. A further enhancement of temperature up to 40
      degrees C had a negative effect on the growth rate, whereas the specific
      monoclonal antibody production rate showed a small increase. The other specific
      metabolic rates also increased in the temperature range between 38 to 40  degrees
      C.

PMID- 22358595
TI  - Comparison of different hepatocyte cell lines for use in a hybrid artificial
      liver model.
AB  - Selection of a cell line suitable for a hybrid artificial liver model employing
      cellulose porous beads (CPBs) was investigated. Hep G2 cells grown in a culture
      dish exhibited appreciably higher ureogenesis and gluconeogenesis activities than
      those grown in CPBs. SEM observation of CPBs revealed marked difference in the
      distribution of attached cells from one bead to another, and showed that almost
      all the cell-bearing micropores were completely packed with cells.With the aim of
      selecting a cell line not prone to excessive aggregation and which grows
      moderately so as not to fill up the micropores, cells of 6 cell lines, HLE, HLF,
      Hep 3B, PLC/PRF/5, Huh 7 and Hep G2, were cultivated in dishes. Hep G2, HLE, and
      HLF increased to 5 * 10(5) cells/cm(2), whereas PLC/PRF/5 grew only to 5 * 10(4),
      and Hep 3B and Huh 7 up to 2 * 10(4) cells/cm(2). The specific activities of
      ureogenesis and gluconeogenesis of Huh 7 were the highest among the lines tested 
      42- and 7-fold those of Hep G2, respectively. When the 6 cell lines were grown
      in a submerged culture with 0.6 g/l of CPBs, Huh 7 had the lowest cell
      concentration of 0.54 * 10(6) cells/ml, and the highest activities of ammonia
      consumption and urea and glucose production (1.38 MU mol NH(3), 99 nmol urea, and
      14.5 nmol glucose/10(6)cells/h). Consequently, Huh 7 is considered to be a
      suitable cell line for use in the development of an artificial liver model
      employing porous beads.

PMID- 22358596
TI  - Optimization of monoclonal antibody production: combined effects of potassium
      acetate and perfusion in a stirred tank bioreactor.
AB  - To increase the yield of monoclonal antibody in a hybridoma culture, it is
      important to optimize the combination of several factors including cell density,
      antibody productivity per cell, and the duration of the culture. Potassium
      acetate enhances the production of antibodies by cells but sometimes depresses
      cell density. The production of anti-(human B-type red blood cell surface
      antigen) antibody by Cp9B hybridoma was studied. In batch cultures, potassium
      acetate inhibited Cp9B cells growth and decreased the maximal cell density but
      the productivity of antibody per cell was increased. The balance of the two
      effects resulted in a slight decline of antibody production. In a stirred tank
      bioreactor, the inhibitory effect of potassium acetate on cell density was
      overcome by applying the perfusion technique with the attachment of a cell
      recycling apparatus to the bioreactor. In such a reactor, potassium acetate at 1
      g l(-1) did not cause a decrease in the cell density, and the antibody
      concentration in the culture supernatant was increased from 28 MUg ml(-1) to 38
      MUg ml(-1). Potassium acetate also suppressed the consumption of glucose and the
      accumulation of lactate in batch cultures, but the glucose and lactate levels
      were kept stable by applying the perfusion technique in the stirred tank
      bioreactor.

PMID- 22358598
TI  - Recombinant protein production using the Semliki Forest Virus expression system.
AB  - We report here the successful scale up of transient recombinant protein
      expression to litre scale using Semliki Forest Virus System. The expression of
      bacterial beta-galactosidase was initially compared in BHK and CHO cells and the
      conditions for optimal infection of BHK cells were identified. 10% FCS in a
      medium at pH 6.9 and infection in small volumes were found to be optimal. A high
      MOI results in an increased recombinant protein yield. Stirring does not affect
      the infection process. Finally we applied these optimal conditions to the
      production of a microsomal enzyme, human cyclooxygenase-2 in suspension spinners.
      Five independant productions at the 1 litre scale yielded reproducible
      substantial amounts of recombinant protein (16 mg microsomal protein 10(9) cells(
      1)) with an average specific activity of 3942 +/- 765 pg PGE(2) MUg(-1)
      microsomal protein 5 min(-1).

PMID- 22358597
TI  - Chinese hamster ovary cells produce sufficient recombinant insulin-like growth
      factor I to support growth in serum-free medium. Serum-free growth of IGF-I
      producing CHO cells.
AB  - Insulin-like growth factor I has similar mitogenic effects to insulin, a growth
      factor required by most cells in culture, and it can replace insulin in serum
      free formulations for some cells. Chinese Hamster Ovary cells grow well in serum
      free medium with insulin and transferrin as the only exogenous growth factors. An
      alternative approach to addition of exogenous growth factors to serum-free medium
      is transfection of host cells with growth factor-encoding genes, permitting
      autocrine growth. Taking this approach, we constructed an IGF-I heterologous gene
      driven by the cytomegalovirus promoter, introduced it into Chinese Hamster Ovary
      cells and examined the growth characteristics of Insulin-like growth factor I
      expressing clonal cells in the absence of the exogenous factor. The transfected
      cells secreted up to 500 ng/10(6) cells/day of mature Insulin-like growth factor
      I into the conditioned medium and as a result they grew autonomously in serum
      free medium containing transferrin as the only added growth factor. This growth
      stimulating effect, observed under both small and large scale culture conditions,
      was maximal since no further improvement was observed in the presence of
      exogenous insulin.

PMID- 22358599
TI  - The indirect effects of multiplicity of infection on baculovirus expressed
      proteins in insect cells: secreted and non-secreted products.
AB  - The baculovirus expression vector system was employed to produce human
      apolipoprotein E and beta-galactosidase in order to study the effect of
      multiplicity of infection on secreted and non-secreted recombinant protein
      production. Prior knowledge of the influence of other cell culture and infection
      parameters, such as the cell density at time of infection and the time of
      harvest, allowed determination of the direct and indirect influences of
      multiplicity of infection on recombinant protein synthesis and degradation in
      insect cells. Under non-limited, controlled conditions, the direct effect of
      multiplicity of infection (10(-1)-10 pfu/cell) on specific recombinant product
      yields of non-secreted beta-galactosidase was found to be insignificant. Instead,
      the observed increased in accumulated product was directly correlated to the
      total number of infected cells during the production period and therefore
      ultimately dependent on an adequate supply of nutrients. Only the timing of
      recombinant virus and protein production was influenced by, and dependent on the
      multiplicity of infection. Evidence is presented in this study that indicates the
      extremely limited predictability of post-infection cell growth at very low
      multiplicities of infection of less than 0.1 pfu/cell. Due to the inaccuracy of
      the current virus quantification techniques, combined with the sensitivity of
      post-infection cell growth at low MOI, the possibility of excessive post
      infection cell growth and subsequent nutrient limitation was found to be
      significantly increased. Finally, as an example, the degree of product stability
      and cellular and viral protein contamination at low multiplicity of infection is
      investigated for a secreted recombinant form of human apolipoprotein E.
      Comparison of human apolipoprotein E production and secretion at multiplicities
      of infection of 10(-4)-10 pfu/cell revealed increased product degradation and
      contamination with intracellular proteins at low multiplicities of infection.

PMID- 22358600
TI  - A practical short course in membrane separations in food processing.

PMID- 22358601
TI  - Preface.

PMID- 22358603
TI  - Normal rat intestinal cells IEC-18: characterization and transfection with
      immortalizing oncogenes.
AB  - IEC-18 cells, a cell line derived from the ileum of rat intestine, have the
      characteristics of normal cells since they have a contact inhibited cell growth,
      do not form colonies in soft agar and are not tumorigenic when injected in nude
      mice. IEC-18 cells were transfected with nuclear oncogenes, c-myc, v-myc and SV40
      T antigen in order to obtain immortal cell lines. Independent clones were
      isolated and characterized for the growth properties. Expression of v-myc altered
      the morphology of the cells and shortened the doubling time. A slow growth
      together with a low cloning efficiency was associated with the expression of SV40
      T antigen. No changes either in growth or in morphology were observed in c-myc
      expressing IEC-18 cells. Expression of these nuclear oncogenes did not result in
      the neoplastic transformation of the IEC-18 cells, since none of the clones lost
      the anchorage dependence or were able to form tumors in vivo. The c-myc
      containing IEC-18 cells were unable to secrete in the growth medium TGF alpha and
      exposure to TGF beta inhibited the growth rate by 30%. All these observations are
      consistent with the conclusion that the expression of nuclear oncogenes does not
      lead to the neoplastic transformation of these cells.

PMID- 22358604
TI  - A new apparatus for studying the effect of hydrostatic pressure on cells in
      culture : application to osteoblastic cells ROS 17/2.8.
AB  - Although mechanical stresses have long been recognized as an important factor in
      the regulation of bone remodeling, the mechanism underlying this effect has
      remained obscure. A number of methods have been devised to apply forces to bone
      tissues and bone-derived cells in order to investigate the biochemical results of
      mechanical stimuli. In this paper we report a method for applying a well
      controlled cyclic hydrostatic pressure on cultured ROS 17/2.8 osteoblastic
      lineage cells. This technique allows the investigation of the true frequency
      response of cells. Hydrostatic pressure with a 1 Hz frequency decreases alkaline
      phosphatase activity of confluent osteoblastic-like cells (ROS 17/2.8).

PMID- 22358605
TI  - Long-term culture of functional hepatocytes on chemically modified collagen gels.
AB  - For long-term maintenance of functional hepatocytes in primary culture, a new
      culture system with chemically modified type-I collagen gel was developed.
      Isolated hepatocytes spread as flat cells and rapidly lost their viability and
      functions when cultured on native collagen gel. In contrast, they survived for
      several weeks when cultured on collagen gels that had been modified by treatment
      with sodium-borohydride (NaBH(4)) or by digestion with pepsin, which resulted in
      destruction of crosslinking of collagen fibers and marked decrease in meachanical
      strength of the gels. These long-lived cells were round and aggregated and
      maintained high levels of various differentiated liver functions including
      albumin secretion and activities of tyrosine aminotransferase and P450. Moreover
      on collagen gels modified by treatment with NaBH(4) or pepsin, the cell showed
      less DNA synthesis in response to mitogenic stimulation than cells cultures on
      gel containing native collagen. Interestingly, crosslinking of these chemically
      modified gels with D-ribose resulted in changes in various phenotypes of
      hepatocytes cultures on them including shape, longevity, and functions expressed
      when the cells were cultured on native collagen gel, suggesting that the effect
      of modification of the collagen gel is reversible. Thus the structure of collagen
      gels, probably due to the degree of crosslinking, seems to affect the morphology,
      maintenance of differentiated functions, and growth of primary cultured
      hepatocytes.

PMID- 22358606
TI  - Death rate in a small air-lift loop reactor of vero cells grown on solid
      microcarriers and in macroporous microcarriers.
AB  - The death rate of Vero cells grown on Cytodex-3 microcarriers was studied as a
      function of the gas flow rate in a small air-lift loop reactor. The death rate
      may be described by first-order death-rate kinetics. The first-order death-rate
      constant as calculated from the decrease in viable cells, the increase in dead
      cells and the increase in LDH activity is linear proportional to the gas flow
      rate, with a specific hypothetical killing volume in which all cells are killed
      of about 2.10(-3) m(3) liquid per m(3) of air bubbles. In addition, an experiment
      was conducted in the same air-lift reactor with Vero cells grown inside porous
      Asahi microcarriers. The specific hypothetical killing volume calculated from
      this experiment has a value of 3.10(-4) m(3) liquid per m(3) of air bubbles,
      which shows that the porous microcarriers were at least in part able to protect
      the cells against the detrimental hydrodynamic forces generated by the bubbles.

PMID- 22358607
TI  - Scale up cultivation of primary human umbilical vein endothelial cells on
      microcarriers from spinner vessels to bioreactor fermentation.
AB  - Five types of dextran-based microcarriers (Dormacell(TM), Pfeifer and Langen)
      with different concentrations of dimeric DEAE anion-exchange groups (nitrogen
      contents from 1.2 up to 2.9%) were tested as growth substrates for the
      cultivation of human umbilical vein endothelial cells (HUVECs). All microcarriers
      were gelatinized before use to improve cell adhesion. The one with the highest
      DEAE-group density was found to be most suitable for HUVEC propagation reaching
      final cell densities of 8*10(5) viable cells ml(-1) (95% viability) using
      microcarrier concentrations of 3 g l(-1). Furthermore, metabolic data of
      glucose/lactate and amino acid metabolism are presented in this study. The
      concentrations of 18 amino acids were monitored throughout cultivation. A
      considerable decrease of glutamine and inverse increase of glutamate was
      observed. Cultivation with initial glucose concentration of 16.5 mmol l(-1)
      resulted in high glutamine consumption rates, whereas high glucose-supplemented
      starting culture medium (30 mmol l(-1)) gave considerably lowered rates,
      indicating altered glutamine metabolism due to different glucose feeding. The
      glucose consumption and lactate production rates increased 2.6 fold and 3.5 fold,
      respectively, due to switch over from low to high glucose supplemented cultures.
      The rate of glucose metabolism was found not to be directly related to cell
      growth, because almost identical growth rates and doubling times were obtained.
      Considering the remaining 16 amino acids measured, serine concentrations
      considerably declined and glycine as well as alanine concentrations raised
      strongly. Most amino acid values were found insignificantly altered during 14
      days of cultivation. Spinner vessel cultures served as inoculum for up scale
      propagation of HUVECs in membrane stirred 2 liter bioreactors. About 5*10(9)
      HUVECs were produced, which were used for the isolation and structural
      characterization of glycosphingolipids, cell membrane compounds, which are
      suggested to be involved in e.g. selectin-carbohydrate interaction (cell-cell
      adhesion), carcinogenesis and atherogenesis.

PMID- 22358608
TI  - The crystal violet nuclei staining technique leads to anomalous results in
      monitoring mammalian cell cultures.
AB  - Nuclear counts determined by crystal violet staining from samples of stationary
      or microcarrier cultures of hybridomas, CHO or Vero cells were consistently and
      significantly higher than cell concentrations determined by the trypan blue or
      Coulter counter methods. This difference was attributed to the presence of a
      significant proportion of binucleated cells, which are assumed to be 35% of the
      cell population in the stationary phase of Vero cultures. The proportion of such
      cells during exponential growth was variable. However, continuous sub-culture of
      these cells induced a degree of synchrony during growth which resulted in a
      cyclic variation of the difference between the cell and nuclei counting
      techniques. This data indicates that care should be taken in interpreting cell
      culture profiles based solely on crystal violet nuclei staining counts.

PMID- 22358610
TI  - "Shylock" revisited.

PMID- 22358609
TI  - Cell suicide in starving hybridoma culture: survival-signal effect of some amino
      acids.
AB  - Two mouse hybridoma cell lines cultured in different basal media with the iron
      rich protein-free supplement were subjected to deliberate starvation by
      inoculation into media diluted with saline to 50% or less. In the diluted media
      the growth was markedly suppressed and a large fraction of cells died by
      apoptosis. The cells could be rescued from apoptotic death by individual
      additions of amino acids, such as glycine, L-alanine, L-serine, L-threonine, L
      proline, L-asparagine, L-glutamine, L-histidine, D-serine, beta-alanine or
      taurine. Amino acids with hydrophobic or charged side chains were without effect.
      The apoptosis preventing activity manifested itself even in extremely diluted
      media, down to 10% of the standard medium. The activity of L-alanine in the
      protection of cells starving in 20% medium was shown also in semicontinuous
      culture. In the presence of 2 mM L-alanine the steady-state viable cell density
      more than doubled, with respect to control, and the apoptotic index dropped from
      37% in the control to 16%. It was concluded that the apoptosis-preventing amino
      acids acted as signal molecules, rather than nutrients, and that the signal had a
      character of a survival factor. The specificity of present results, obtained with
      two different hybridomas, supports our view (Franek and Chladkova-Sramkova, 1995)
      that the membrane transport macromolecules themselves may play the role of the
      recognition elements in a signal transduction pathway controlling the survival of
      hybridoma cells.

PMID- 22358611
TI  - Membranous nephropathy in Japan: analysis of the Japan Renal Biopsy Registry (J
      RBR).
AB  - Membranous nephropathy (MN) is one of the most common causes of nephrotic
      syndrome in adults. The J-RBR/J-KDR registry developed by the Japanese Society of
      Nephrology provides nationwide cohort data for epidemiological studies of MN. MN
      was present in 36.8% of 1,203 primary nephrotic syndrome patients in Japan. In
      addition, 633 (77.9%) out of 813 MN patients were referred to as "idiopathic,"
      whereas 22.1% were classified as "secondary" and involved conditions such as
      systemic lupus erythematosus, drug exposure, infections, cancer, and various
      collagen diseases. The mean age of the MN patients was 62.2 (2-88) years old,
      their mean eGFR was 76.7 (7.6-154.6) ml/min/1.73 m(2), and 63.3% had hypertension
      at the time of renal biopsy. On the basis of these findings, half of Japanese
      idiopathic MN patients have risk factors (age >60, male, or lower eGFR) for end
      stage renal failure, and 10% belong to the high-risk group (daily proteinuria of
      over 8.0 g). Further studies with high-grade evidence should resolve the natural
      history and therapeutic problems of idiopathic MN in elderly Japanese.

PMID- 22358612
TI  - Association between the rate of low-birth weight newborns and the incidence of
      end-stage renal disease in 47 prefectures in Japan.
AB  - BACKGROUND: An ecological study is a useful epidemiologic tool for public health
      surveillance and establishment of a new hypothesis. Here, we used an ecological
      study to analyze the association between birth weight and end-stage renal disease
      (ESRD). METHODS: We performed ecological regression analysis by using data
      obtained from the national database of Japan. The data include regional incidence
      of ESRD beginning maintenance dialysis therapy, regional rate of low-birth weight
      (LBW) newborn babies of all newborn babies, the average birth weight of newborns,
      the body mass index (BMI) score, the prevalence of diabetes mellitus, and the
      amount of payment for drugs, in the 47 prefectures of Japan. RESULTS: The mean
      regional rates of LBW newborn babies from 1999 to 2008 statistically correlated
      with the mean incidences of ESRD during the same time periods in each prefecture.
      The correlation coefficients between the yearly rate of LBW newborns and the
      yearly incidence of ESRD in each prefecture became higher after statistically
      considering the effects of the cost per resident for prescriptions of angiotensin
      II receptor blocker and angiotensin converting enzyme inhibitor. Furthermore, the
      final model predicting the regional incidence of ESRD by a stepwise multiple
      regression analysis consisted of the average BMI score and the rate of LBW
      newborns in each prefecture. CONCLUSION: Although this study cannot explain the
      reason for this unexpected correlation between the regional rate of LBW babies
      and the regional incidence of ESRD at the same time points, the statistically
      significant correlations shown in this study should be taken into consideration.

PMID- 22358613
TI  - A lower level of reduced albumin induces serious cardiovascular incidence among
      peritoneal dialysis patients.
AB  - BACKGROUND: Human serum albumin is composed of human mercaptoalbumin (HMA) with
      cysteine residues having reducing powers and of oxidized human non
      mercaptoalbumin. Previously, we reported that a lower HMA level is closely
      related to serious cardiovascular disease (CVD) incidence and mortality among
      hemodialysis patients. However, the relationship between HMA level and CVD
      incidence among peritoneal dialysis (PD) patients is unclear. METHODS: We
      measured the redox state of human serum albumin using high-performance liquid
      chromatography in 30 continuous ambulatory PD patients. The association between
      HMA and incidental CVD events was evaluated. RESULTS: Eight patients experienced
      symptomatic CVD events (5 patients died) at the 5-year follow-up. The
      concentration and fraction of HMA (cHMA and f(HMA), respectively) showed
      significantly lower values in patients with CVD than those without CVD (cHMA 1.58
      +/- 0.39 and 2.16 +/- 0.43 g/dL, f(HMA) 48.9 +/- 5.4 and 56.4 +/- 8.6%,
      respectively). Multiple forward stepwise regression analysis using cHMA and
      f(HMA) as the criterion variables was performed, and C-reactive protein and
      hemoglobin were adopted as significant explanatory variables in the former
      equation, whereas urea nitrogen was adopted in the latter equation. Multiple
      logistic regression analysis revealed that cHMA is a statistically, and f(HMA) is
      a marginally significant explanatory variable of CVD incidence (p = 0.0369, R = 
      0.260 and p = 0.0580, R = -0.214, respectively). CONCLUSIONS: Lower HMA level,
      which might be caused by chronic inflammation, anemia and accumulation of
      dialyzable uremic toxin(s), is closely related to serious CVD incidence among PD
      patients.

PMID- 22358614
TI  - Porcine blood cell separation by porous cellulose acetate membranes.
AB  - Leukocytes were separated from whole porcine blood using laboratory prepared
      polymeric asymmetric porous membranes from cellulose acetate (CA) and by applying
      standard blood cell separation methods: centrifugation in a Ficoll solution
      gradient and in sucrose solution concentration gradient. Leukocytes, obtained by
      different separation methods were characterised by their quantity, type,
      viability and growth ability. Membranes prepared by a wet phase inversion process
      from different cellulose acetate/acetone/water and magnesium chlorate VII
      systems, were characterised according to: permeability to deionised water,
      surface morphology and by the determination of the flux of the permeate during
      the whole porcine blood separation. Cellulose acetate membranes prepared from 300
      MUm thick cast solution (14.8 wt% of cellulose acetate, 19.9 wt% of water, 2.3
      wt% of Magnesium perchlorate, and 63.0 wt% of acetone), have separation
      characteristics comparable with the standard separation methods; in the dead-end
      mode filtration, 21.3% of leukocytes from porcine whole blood are separated. The
      leukocyte number in peripheral blood before separation was 450,000 ml(-1); the
      number passed through after was 95,000+/-6620. The main interest of the study was
      to introduce the CA membrane filters for the continus technological separation of
      the leukocyte/lymphocytes from animal (= porcine, bovine, horse..) blood.

PMID- 22358616
TI  - Effects of dissolved oxygen levels and the role of extra- and intracellular amino
      acid concentrations upon the metabolism of mammalian cell lines during batch and
      continuous cultures.
AB  - The effects of dissolved oxygen and the concentration of essential amino acids
      upon the metabolism of two mammalian cell lines (rCHO producing human active (t
      PA) and a mouse-mouse hybridoma) were investigated in batch, chemostat, and
      perfusion cultures. Intracellular amino acid concentrations were measured for
      both cell lines during repeated batch cultures and the K(S)-values for the
      essential amino acids were calculated using Monod equations via computer
      simulation. The K(S)-values were in the range of 10 mmol L(-1) and the pool of
      most intracellular amino acids remained constant at about 10-100 fold higher in
      concentration than in the medium. No significant differences were observed
      between the hybridoma and CHO cell. The specific nutrient uptake rates
      corresponded with the cell specific growth rate and the effects of reduced
      dissolved oxygen concentrations only became evident when the DO dropped below 5%
      of air saturation (critical concentration below 1%). Nevertheless, a correlation
      between nutrient concentration and specific oxygen uptake was detected.

PMID- 22358615
TI  - Incidence and potential implications of the toxic metabolite methylglyoxal in
      cell culture: A review.
AB  - Methylglyoxal is a toxic metabolite unavoidably produced in mammalian systems as
      a by-product of glycolysis. Detoxification of this compound occurs principally
      through the glyoxalase pathway, which consists of glyoxalase I and glyoxalase II,
      and requires reduced glutathione as a co-enzyme. Recently, it has been
      demonstrated that variations in glucose, glutamine and fetal bovine serum levels
      can cause significant changes in the intracellular concentration of
      methylglyoxal. More importantly, comparative studies involving wild-type Chinese
      hamster ovary cells and clones overexpressing glyoxalase I indicate that glucose
      and glutamine, within the range normally found in cell culture media, can cause
      decreased cell viability mediated solely through increased production of
      methylglyoxal. In addition, endogenously produced methylglyoxal has been shown to
      cause apoptosis in cultured HL60 cells. While the exact mechanism of the impact
      of methylglyoxal on cultured cells is unknown, methylglyoxal is a potent protein
      and nucleic acid modifying agent at physiological concentrations and under
      physiological conditions. Protein modification occurs mainly at arginine, lysine
      and cysteine residues and is believed to be an important signal for the
      degradation of senescent proteins. Modification of arginine and lysine results in
      the irreversible formation of advanced glycation endproducts, whereas
      modification of cysteine results in the formation of a highly reversible
      hemithioacetal. Methylglyoxal also forms adducts with nucleic acids, principally
      with guanyl residues. At high extracellular concentrations, it is genotoxic to
      cells grown in culture. Even at physiological concentrations (100 nM free
      methylglyoxal), methylglyoxal can modify unprotected plasmid DNA and cause gene
      mutation and abnormal gene expression.

PMID- 22358617
TI  - Thrombopoietin stimulates proliferation and megakaryocytic differentiation of
      mouse pro-B cell line BF-TE22.
AB  - We have isolated and characterized a thrombopoietin (TPO)-dependent BF-TE22 cell
      line endogenously expressing murine Mpl, which is a subclone of murine pro-B
      Ba/F3 cells. TPO stimulated the proliferation of BF-TE22 cells in a dose
      dependent manner, and also induced the expression of megakaryocyte lineage
      specific AP-51 and CD61 cell surface antigens. The results indicate that the
      murine Mpl on BF-TE22 cells can transmit both proliferation and megakaryocyte
      lineage-specific differentiation signals to cells. Furthermore, it was shown that
      IL-3 inhibits the TPO-induced differentiation signals of BF-TE22 cells. These
      results suggest that the signals mediated by IL-3 predominate over those of TPO
      in BF-TE22 cells. Thus, BF-TE22 cells will be useful for the biological and
      biochemical studies of the TPO-Mpl signal transduction mechanism.

PMID- 22358618
TI  - Effect of bcl-2 expression on hybridoma cell growth in serum-supplemented,
      protein-free and diluted media.
AB  - Two transfected hybridoma cell lines TB/C3-bcl2 (overexpressing the Bcl-2
      protein) and TB/C3-pEF (control cell line), were compared in batch suspension
      cultures using a medium supplemented either with horse serum or with a protein
      free, iron-rich supplement. The membrane intact index (percentage of cells with
      intact membranes determined by trypan blue staining) of the TB/C3-bcl2 cell line
      decreased much slower than that of the control cell line during the dying phase
      of the cultures. No significant difference in antibody, lactate and ammonia
      production as well as glucose and glutamine consumption was noted in the
      exponential phase of the experiments. Both cell lines were also compared in batch
      experiments using media diluted with saline to further investigate the effect of
      Bcl-2 under sub-optimal conditions. The Bcl-2 overexpressing cell line again
      exhibited a higher membrane intact index at increasing dilution steps.

PMID- 22358619
TI  - Development of a versatile computer integrated control system for bioprocess
      controls.
AB  - A general approach is described for the implementation of a networked multi-unit
      computer integrated control system. The use of data acquisition hardware and
      graphical programming tools alleviates tedious programming and maintains potency
      and flexibility. One application of the control system, the control of a
      mammalian cell perfusion culture based on a key nutrient glucose concentration,
      was demonstrated. The control system offers customized user interface for all
      process control parameters and allows the flexibility for continued improvement
      and implementation of new tailored functions. The temperature, pH, dissolved
      oxygen and glucose level were accurately controlled.

PMID- 22358620
TI  - Distinct volume distribution of viable and non-viable hybridoma cells: A flow
      cytometric study.
AB  - Light scattering properties of hybridoma cells were examined with flow cytometry.
      Viable and dead cells form two distinct populations. The distribution of the two
      populations changes during a batch culture. the concentration of dead cells
      measured by flow cytometry correlates well to that measured by hemacytometer. The
      distribution based on small-angle light scattering is similar to the distribution
      based on volume as measured by Elzone particle counter. It thus appears that
      viable cells form the population with a larger mean cell volume. The results also
      indicate that the volume of viable cells decreases during the cultivation while
      that of dead cells remains relatively constant.

PMID- 22358621
TI  - Production of human-mouse chimeric antibody by high cell density perfusion
      culture.
AB  - Two mouse myeloma cell lines which were transfected with chimeric mouse variable
      human constant immunoglobulin heavy and light chain genes have been cultured at
      high cell density in a settling perfusion culture vessel to produce chimeric
      antibody specific for human common acute lymphocytic leukemia antigen
      (cALLA).J558L transfectant proliferated well in a serum-free medium (ITES-eRDF)
      to a viable cell density of 3.7*10(7) cells/ml and produced chimeric antibody to
      a maximum value of 60 MUg/ml in 120 ml scale vessel. X63Ag8.653 transfectant
      reached a density of 1.9*10(7) cells/ml in 1.2 I scale vessel in serum
      supplemented medium (10% FCS-eRDF) and produced chimeric antibody which consisted
      of chimeric gamma and chimeric kappa chains to a maximum value of 5.8 MUg/ml.

PMID- 22358622
TI  - The relationship between serum and cell type on the development of rat and pig
      cultured preadipocytes.
AB  - Stromal-vascular cells from rats and pigs were isolated from adipose tissue and
      used to measure preadipocyte proliferation and differentiation. Cells from rats
      and pigs were grown in either 2.5% pig serum or 2.5% rat serum. Cells were either
      supplemented or unsupplemented with insulin after five days of growth in culture.
      In these cultures, pig fat cells developed as discrete clusters while rat fat
      cells developed as loose clusters or as individual cells. Rat cells had greater
      levels of sn-glycerol phosphate dehydrogenase activity compared to pig cells. Rat
      serum increased soluble protein in plated cells when compared to cells grown in
      pig serum. Pig serum increased glycerol phosphate dehydrogenase specific activity
      when compared to rat serum. In this system, there was no response to insulin. The
      cells grown in rat serum did not resemble adipocytes in regard to the presence of
      large lipid droplets (oil red 0 staining). These results demonstrate that rat and
      pig stromal-vascular cells in culture are morphologically different. Cells from
      both species, however, responded similarly to sera from either species showing
      that cells from rats and pigs responded to the growth and differentiation factors
      present in these sera.

PMID- 22358623
TI  - Effect of retinoic acid on the proliferation and tumorigenicity of mouse
      mastocytoma cells : Effect of retinoic acid on mastocytoma cells.
AB  - Retinoic acid (RA) inhibited the in vitro growth of the mouse mast cell tumor
      line P(815) in a dose- and time-dependent manner. The inhibition was accompanied
      by an increase in the amount of neutral intracellular mucopolysaccharides. Study
      of cell cycle kinetics showed that exposure to retinoic acid led to a slowing
      down of the cell-cycle progression possibly related to a more differentiated cell
      population disclosed by microscopy with a lower proliferative capacity. In vivo,
      delays in both tumor appearance and mouse mortality were observed after injecting
      RA into mice bearing mastocytomas. These results suggest that RA could be of
      interest in the treatment of human malignant systemic mastocytosis with
      proliferation of immature mast cells.

PMID- 22358624
TI  - Influence of amino acids on hybridoma cell viability and antibody secretion.
AB  - It is generally accepted that the phase of cell decline observed in batch culture
      of mammalian cells is related to exhaustion of medium nutrients (principally
      glucose and glutamine) and/or to waste products accumulation. In the present
      paper, we have studied the influence of glutamine on the proliferation of mouse
      hybridoma cells. We showed that repeated addition of glutamine prolonged the life
      span of the culture and significantly increased the secretion of monoclonal
      antibody. Flow cytometry analysis suggests that this effect of glutamine is
      related to a delay in cell death rather than to a stimulation of
      proliferation.Addition of glutamine and glucose failed however to prevent the
      death of the culture. Determinations of amino acid consumption in glutamine
      supplemented samples and experiments carried out with complementary sources of
      amino acids (e.g. tryptose phosphate) strongly suggest that amino acid supply is
      a critical factor governing cell growth and productivity.

PMID- 22358625
TI  - Optimization of the technique of cell migration from explants: Application to
      human synoviocytes on cryoprecipitate coating.
AB  - The explant technique, though easy to carry out, is unpredictable and thus not
      readily reproducible. Addition of cryoprecipitate, which is rich in fibronectin,
      serves to optimize this technique of cell migration from explants by improving
      adhesion.

PMID- 22358626
TI  - Initial culture conditions affect the sensitivity of HepG2 cells to excessive
      mechanical agitation.
AB  - Hepatoma cells, HepG2, grew normally on microcarriers even at a relatively high
      agitation rate if sufficient time was allowed for cell attachment and adhesion.
      However, if a high agitation rate was applied shortly after initial cell
      attachment, the growth rate was retarded. This sensitivity to mechanical
      agitation appears to be dependent on the inoculation cell density.

PMID- 22358627
TI  - Production of erythropoietin by BHK cells growing on the microcarriers trapped in
      alginate gel beads.
AB  - Baby hamster kidney (BHK) cells engineered to produce recombinant human
      erythropoietin (EPO) were cultured at high density on microcarriers entrapped by
      calcium alginate gel particles. In this system, the BHK cells proliferated not
      only on the microcarriers but also in vacant spaces in the alginate gel
      particles. These spaces contributed greatly to high-density cultivation of the
      cells and a high productivity of EPO.

PMID- 22358628
TI  - Advances in animal cell biology and technology for bioprocesses.

PMID- 22358629
TI  - Animal cell culture: Towards the 21st century.

PMID- 22358630
TI  - Are we prepared for animal cell technology in the 21st century?
AB  - Large scale animal cell culture for the production of complex therapeutic
      proteins has been a major success of the biotechnology industry. Today,
      approximately half of the $ 5 billion annual turnover of the biotechnology
      industry is based upon this technology, in many cases with reactors of more than
      10 m(3). As we look towards the 21 st century, however, we can see novel
      approaches to the production of therapeutic proteins, by means of gene and
      cellular therapies. These technologies present new engineering challenges to the
      animal cell technologist. Are we prepared to meet these challenges? The needs
      include: small-scale reactors for the preparation of autologous cell lines,
      methods for the production of viruses to be used as vectors in gene therapy,
      artificial organ and the processing of xenogenic cell lines and tissues for
      cellular implants in humans. More attention should be given to three-dimensional
      cell cultures. Mass transfer considerations need to be extended beyond just
      oxygen transfer, to include cellular communication in small systems; this is
      becoming increasingly important for the control and optimise growth and product
      formation. Apart from improvements of large-scale systems, substantial advantages
      could be gained by studying new methods for the production and delivery of
      therapeutic proteins, using small-scale cell culture systems. We should adapt
      teaching, regulatory, patent and clinical infrastructure to meet this challenge
      in a harmonious way.

PMID- 22358631
TI  - The acceptability of continuous cell lines: A personal & historical perspective.
AB  - In the 1950s, only primary cell cultures were acceptable for the production of
      human biological products. This position was challenged in the late 1960s by
      human diploid cells (HDCs), and again in the 1980s by continuous cell lines
      (CCLs). The history of the HDC controversy is reviewed and lessons from that era
      that are relevant to the use of CCLs are pointed out. It became apparent in the
      early days of recombinant DNA technology in the 1980s that CCLs were needed for
      the development of some products. CCL acceptability therefore became more urgent,
      and several attempts were made to reach a consensus on regulatory issues. In
      1986, the World Health Organization convened a Study Group to review the safety
      issues related to products derived from CCLs. The Study Group made a clear
      recommendation to pursue CCLs in product development because of the demonstrated
      capability of modern manufacturing processes to cope with contaminants. Issues
      such as acceptable levels of cellular DNA in products and the relationship of
      purity to safety are discussed in the context of the need for regulatory
      authorities, industry, and the general biomedical community to cooperate in
      addressing problems in a rational scientific manner.

PMID- 22358632
TI  - Acceptability of continuous cell lines for the production of biologicals.

PMID- 22358633
TI  - Viral validation strategy for recombinant products derived from established
      animal cell lines.
AB  - For products derived from continuous cell lines, regulatory agencies worldwide
      require that the purification process be validated for its ability to remove or
      inactivate potential contaminants such as viruses and virus-like particles. New
      guidance suggests a requirement for statistical evaluation of these studies but
      the industry has yet to develop such standards. The task of estimating excess
      capacity is also complicated by variable assays, accumulation of variability in
      clearance estimates over unit operations, dependence of clearance capacity on
      operating parameters, and expense of experiments. We propose an experimental
      strategy to determine the excess clearance capacity of a biopharmaceutical
      process and to provide statistical estimation of excess capacity in an efficient
      way. Clearance estimates and their variances are calculated for each orthogonal
      unit operation and estimates are combined to form an interval estimate of overall
      process clearance capacity. Poisson regression is suggested as an efficient
      technique for data analysis of clearance studies. We believe that this approach
      should meet regulatory guidelines in a cost effective way, while clarifying the
      roles of qualitative and quantitative components in setting requirements.

PMID- 22358634
TI  - Oxygen gradients in animal-cell bioreactors.
AB  - An estimation is made of oxygen gradients in animal-cell bioreactors, using
      straightforward engineering calculations. Three types of bioreactor are
      considered: stirred vessel, bubble column and air lift, of sizes between 0.01 and
      10 m(3). First, the gradient is estimated in the stagnant layer surrounding a
      cell (15 MUm), a microcarrier (185 MUm) with 300 cells attached to it, a
      macroporous support (1.25 mm) containing 185,00 cells and one (6 mm) containing
      4.25 million cells. It is assumed that oxygen consumption is 10(-16) mole
      O(2).cell(-1).s(-1), while mass transfer coefficients are obtained from Sherwood
      relations. Circulation and liquid-retention times of the bioreactors are compared
      with the oxygen-exhaust times of suspensions with 10(12), 10(13) and 10(14)
      cells/m(3) to estimate if oxygen gradients are likely to exist in the bulk-liquid
      phase. Finally, the gradient in the liquid film surrounding air bubbles is
      estimated using k( l )A-values obtained from empirical correlations. It is clear
      from all these estimations that in many situations severe gradients can be
      expected. The question remains, however, whether gradients should be avoided as
      much as possible, or may be tolerated to a certain extent or even created on
      purpose because of possible beneficial effects.

PMID- 22358635
TI  - Effects of ammonium ion removal on growth and MAb production of hybridoma cells.
AB  - Production of monoclonal antibody against hepatitis B surface antigen was carried
      out by perfusion culture coupled with a selective removal system for ammonium
      ion. The removal system is composed of three sub-systems namely, cell separation
      by cross-flow ceramic filter, dialysis by hollow fiber module and ion-exchange by
      zeolite A-3 packed bed column. The ammonium ion concentration in the culture
      broth was effectively maintained below the inhibitory level, and the viable cell
      density reached 2.5*10(7) cells ml(-1) which was three times that of conventional
      perfusion cultures. The monoclonal antibody accumulated to a concentration as
      high as 26.3*10(5) mIU(-1). This is already almost half of the amount producedin
      vivo. The numerical investigation of the ammonium ion removal system showed the
      possibility to improve much more the performance of this perfusion cultivation
      system.

PMID- 22358636
TI  - Microcarrier technology, present status and perspective.
AB  - Only a decade after Van Wezel introduced the first product made in microcarrier
      cultures on industrial scale at economically acceptable costs, namely Inactivated
      Polio Vaccine (IPV), interest was taken in this revolutionary type of cell growth
      system. The basic idea was to develop a culture system with equal potentials for
      control of environmental culture conditions and scaling up as the systems used in
      industrial microbiology. Although initially only positively-charged beads were
      used it soon became clear that negatively-charged or amphoteric materials such as
      proteins or amino acids polymerized to the surface were equally useful.
      Eventually numerous different types of microcarrier were developed. The second
      generation of microcarriers consisted of macroporous beads providing increased
      surface area for cell attachment and growth by external and interior space. Such
      microcarriers offer great potential for high cell densities and enhanced
      productivity for certain production systems, especially recombinant CHO-cells.
      These carriers, which not only provide possibilities for anchorage-dependent
      cells but also for cells growing suspension, can be used in homogeneous
      bioreactors as well as in fluidized or fixed-bed systems. Despite considerable in
      vestments and research on the development and improvement of microcarriers one
      question is still open: is microcarrier technology still in its infancy or is it
      full-grown and is the basic idea relized? In this paper a general overview will
      be given of the present state of microcarrier technology and also of its
      perspectives.

PMID- 22358637
TI  - Batch control system vaccines: BCSV : A new man machine interface for
      bioreactors.
AB  - The Batch Control System for Vaccines (BCSV), a new Man Machine Interface (MMI)
      for the control of cultivations in bioreactors, was developed according to SP-88.
      SP-88 is the ISA standard for Batch Control Systems. Among others, SP-88 supplied
      the concept of recipes, which organize and specify the monitoring and control
      requirements for manufacturing. Process optimisation and compliance to GMP rules
      and regulations were the main objectives for this development.The most important
      features of the BCSV interface include:  - implementation at production, pilot
      and R & D scale to assure easy transfer of knowledge and experience at the
      various stage of process development;   - independency of underlying hardware to
      ensure similar "look and feel" for different pieces of equipment;   - in-house
      development and maintenance of recipes to have maximum control over applications;
      - interactive communication between operator and BCSV during recipe execution.
      GMP compliance was assured not only by considering governing sets of GMP
      regulations, but also by taking up the interface in a overall Information &
      Automation strategy and by setting up a QA strategy for the entire life cycle of
      the system.

PMID- 22358638
TI  - Proliferation control of mammalian cells by the tumor suppressor IRF-1.
AB  - We have attempted to establish a system in which cell proliferation is controlled
      by a physiological regulator. Interferon regulatory factor 1 (IRF-1) is a
      transcription factor that recognizes a sequence which is present in the
      interferon-beta promoter as well as in the promoters of interferon-inducible
      genes. IRF-1 acts as a tumor suppressor. Constitutive overexpression of
      recombinant IRF-1 leads to inhibition of cell growth. The extent of this growth
      arrest depends on the intracellular concentration of IRF-1. In order to allow IRF
      1 expression in various mammalian cells we have established two different systems
      for conditional IRF-1 transcription and activation, respectively. In one case, an
      inducible promoter, in the other case a fusion protein composed of IRF-1 and the
      hormone-binding domain of the human estrogen receptor was used. Both systems
      allow to control gradually the growth of mammalian cell lines by adjusting the
      intracellular concentration of IRF-1 via estradiol or tetracycline in the medium.
      Despite the activity of IRF-1 as an antiproliferative agent the expression of
      certain proteins is retained. Moreover, expression of genes which are controlled
      by IRF-1 responsive promoters is enhanced.

PMID- 22358639
TI  - Protein folding in the secretory pathway of animal cells.
AB  - The exit of newly-synthesized proteins from the lumen of the endoplasmic
      reticulum (ER) is the rate-determining step in protein secretion. Only correctly
      folded and fully-assembled proteins exit the ER and progress along the secretory
      pathway. Folding and assembly in the ER are mediated by a variety of factors
      including folding catalysts and molecular chaperones. The properties of these
      factors, and the nature of their interactions with folding substrates, are
      beginning to be clarified. Little work has been done to characterize these
      processes and these factors in cell lines employed for large-scale cell culture.
      Manipulation of these process may permit improvement in yield or productivity of
      recombinant proteins by cultured animal cells.

PMID- 22358640
TI  - Erythropoietin processing in erythropoietic system and central nervous system.
AB  - We describe possible functions of carbohydrates attached to growth factors and
      strategies to examine the functions, concentrating on erythropoietin, a major
      regulator of erythropoiesis. Erythropoietin in erythropoiesis functions as an
      endocrine hormone; it is produced by kidney cells and transferred into the
      circulation to hemopoietic sites. In the brain, erythropoietin acts on neurons in
      a paracrine fashion. Comparison of glycosylation has been made between kidney and
      brain erythropoietins.

PMID- 22358642
TI  - Functional display of proteins, mutant proteins, fragments of proteins and
      peptides on the surface of filamentous (bacterio) phages: A review.
AB  - Cytoplasmic expression of complex eukaryotic proteins inEscherichia coli usually
      yields inactive protein preparations. In some cases, (part) of the biological
      activity can be recovered by rather inefficient denaturation-renaturation
      procedures. Recently, novel concepts have been developed for the expression of
      fully functional eukaryotic proteins inE. coli. Essential to the success of these
      procedures is the transport of such proteins across the inner membrane to the
      periplasmic space, allowing proper folding and the establishment of disulfide
      bonding. Subsequently, fully functional proteins can be exposed on the surface of
      filamentous (bacterio)phages, provided a system is employed that consists of a
      cloning vector (e.g. the phagemid pComb3, Barbas et al., 1991) that generates
      phage particles in the presence of a helper phage. The main advantage of surface
      display of recombinant proteins is to facilitate the screening of very large
      numbers of different molecules by simple selection methods ("panning"). In
      addition, periplasmic expression yields relatively large quantities (e.g. 1 mg l(
      1) of culture) soluble protein. In this review, the principle aspects of this
      novel expression system based on the phagemid pComb3 will be discussed. Two
      examples for functional periplasmic expression of human proteins inE. coli will
      be presented, namely i) the antigen-binding moiety (Fab fragment) of human
      immunoglobulins (IgGs) and ii) the human plasminogen activator inhibitor 1, an
      essential regulator of the plasminogen activation system. Finally, perspectives
      for the application of this system to express mutant proteins, fragments of
      proteins and peptides are indicated.

PMID- 22358643
TI  - Apoptosis and nutrition: Involvement of amino acid transport system in repression
      of hybridoma cell death.
AB  - Mouse hybridoma cells cultured on the verge of starvation-induced apoptosis, i.e.
      in a medium diluted with saline, proved to serve as a sensitive screening system
      for apoptosis-suppressing activity of nutrient medium components. Conventional
      amino acid mixtures were found to suppress the starvation-induced apoptosis,
      whereas a vitamin mixture was ineffective. (Franek F (1995) Biotechnol. Bioeng.
      45: 86-90). Recent experiments showed that suppression of apoptosis, and
      concurrent resumption of growth, could be achieved by addition of single
      substances at millimolar concentrations. The set of active substances included
      certain coded L-amino acids (glycine, alanine, serine, threonine, proline,
      asparagine, glutamine, histidine), non-coded amino acids (beta-alanine, taurine,
      4-aminobutyric acid), and a non-metabolizable analogue (2-aminoisobutyric acid).
      This finding shows that some amino acids do not act solely as nutrients, but also
      as specific signal molecules. The specificity of the effect points to the
      involvement of adaptively regulated amino acid transport systems A and N in
      maintaining the balance between triggering and suppression of starvation-induced
      apoptosis.

PMID- 22358644
TI  - Transfer and expression of the human multiple drug resistance gene as potential
      human gene therapy.
AB  - The human multiple drug resistance (MDR) gene has been used as a model for human
      gene transfer which could lead to human gene therapy. MDR is a transmembrane
      protein which pumps a number of toxic substances out of cells including several
      drugs used in cancer chemotherapy. Normal bone marrow cells express low levels of
      MDR and are particularly sensitive to the toxic effects of these drugs. There are
      two general applications of MDR gene therapy: (1) to provide drug-resistance to
      the marrow of cancer patients receiving chemotherapy, and (2) as a selectable
      marker which when co-transferred with a non-selectable gene such as the human
      beta globin gene can be used to enrich the marrow for cells containing both
      genes. We demonstrate efficient transfer and expression of the human MDR gene in
      a retroviral vector into live mice and human marrow cells including CD34(+) cells
      isolated from marrow and containing the bulk of human hematopoietic progenitors.
      MDR gene transduction corrects the sensitivity of CD34(+) cells to taxol, an MDR
      drug substrate, and enriches the marrow for MDR-transduced cells. The MDR gene
      containing retroviral supernatant used has been shown to be safe and free of
      replication-competent retrovirus. Because of the safety of the MDR retroviral
      supernatant, and efficient gene transfer into mouse and human marrow cells, a
      phase 1 clinical protocol for MDR gene transfer into cancer patients has been
      approved to evaluate MDR gene transfer and expression in human marrow.

PMID- 22358641
TI  - Monitoring of immunotherapy with cytokines or monoclonal antibodies.
AB  - Recombinant cytokines and monoclonal antibodies (mAbs) are increasingly used in
      the treatment of a number of human diseases. Monitoring of the clinical efficacy
      of these agents requires specific clinical and laboratory measurements. A number
      of these novel therapies share common side effects, ranging from fever, headache
      and general malaise to hypotension, the development of edema leading to the
      vascular leak syndrome, the occurrence of thromboembolic processes and, in severe
      cases, organ dysfunction. As an example of the pathogenesis of these side
      effects, recent data are presented which were obtained in patients receiving
      immunotherapy with high doses of the cytokine interleukin-2 as an anti-cancer
      treatment.

PMID- 22358645
TI  - Replating of bioreactor expanded human bone marrow results in extended growth of
      primitive and mature cells.
AB  - The capability to expand human bone marrow mononuclear cells (BM MNC) in high
      density perfusion culture chambers (bioreactors) has recently been developed. In
      these bioreactors, total cell colony-forming unit-granulocyte/macrophage (CFU
      GM), and long-term culture-initiating cell (LTC-IC) numbers increase
      significantly over a 14-day period. However, cell growth ceases after the 14-day
      period, possibly due to cell density limitations. Because of the remaining
      presence of early cells, it should be feasible to replate the cells and obtain
      continued expansion. In this study, we demonstrate that bioreactors generate
      cells, which upon replating into secondary bioreactors, lead to continued cell,
      CFU-GM, and LTC-IC(8) (measured after 8 weeks of secondary culture) expansion. A
      two-stage protocol, involving the replating of cells on days 9 to 12 of culture
      into new bioreators at the original seeding density, yielded greater than 50-fold
      cell expansion from BM MNC in 25 days. CFU-GM were expanded inhibitory factor
      (LIF) had no significant effect on total cells, CFU-GM, or LTC-IC(5) in this
      system. We conclude that two-stage bioreactor cultures are capable of supporting
      extended growth of human BM MNC, CFU-GM, and LTC-IC(8). The continued expansion
      of these primitive cells in the second stage of culture suggests that primitive
      cells with significant proliferative potential were generated in this system, and
      previous data on LTC-IC(5) expansion has now been extended to LTC-IC(8)
      expansion. Further optimization of culture conditions is likely to improve on the
      results obtained here, thus making perfusion bioreactor culture correspondingly
      more attractive for expanding BM MNC for BM transplantation.

PMID- 22358647
TI  - ESACT meeting overview: Back to the future.

PMID- 22358646
TI  - Ex vivo expansion of primitive hematopoietic cells for cellular therapies: An
      overview.
AB  - Sources of hematopoietic cells for bone marrow transplantation are limited by the
      supply of compatible donors, the possibility of viral infection, and autologous
      (patient) marrow that is depleted from prior chemo- or radiotherapy or has
      cancerous involvement. Anex vivo system to amplify hematopoietic progenitor cells
      could increase the number of patients eligible for autologous transplant, allow
      use of cord blood hematopoietic cells to repopulate an adult, reduce the amount
      of bone marrow and/or mobilized peripheral blood stem and progenitor cells
      required for transplantation, and reduce the time to white cell and platelet
      engraftment. The cloning of hematopoietic growth factors and the identification
      of appropriate conditions has enabled the development of successfulex vivo
      hematopoietic cell cultures. Purification systems based on the CD34 marker (which
      is expressed by the most primitive hematopoietic cells) have proven an essential
      tool for research and clinical applications. Present methods for hematopoietic
      cultures (HC) on stromal (i.e. accessory cells that support hematopoiesis) layers
      in flasks lack a well-controlled growth environment. Several bioreactor
      configurations have been investigated, and a first generation of reactors and
      cultures has reached the clinical trial stage. Our research suggests that
      perfusion conditions improve substantially the performance of hematopoietic
      reactors. We have designed and tested a perfusion bioreactor system which is
      suitable for the culture of non-adherent cells (without stromal cells) and
      readily scaleable for clinical therapies. Eliminating the stromal layer
      eliminates the need for a stromal cell donor, reduces culture time, and
      simplifies the culture system. In addition, we have compared the expansion
      characteristics of both mononuclear and CD34(+) cells, since the latter are
      frequently assumed to give a superior performance for likely transplantation
      therapies.

PMID- 22358649
TI  - Some myths and messages concerning the batch and continuous culture of animal
      cells.
AB  - lt is often assumed that continuous processes are more difficult and less
      productive than a suite of batch processes for the production of a particular
      biomolecule. This paper cites two papers which have appeared in the literature
      which propound this view and examines in detau the justification for the support
      of this contention. After reviewing those features where it is alleged that
      continuous processes are at a disadvantage, the authors of this paper conclude
      that the opposite is the case and that for suitable processes the most effective
      way of generating product is by the use of fully continuous processes. The choice
      of a particular process dependends on a variety of fixed and variable factors
      which are unique to the process. These factors are discussed and two decision
      trees are presented which are designed to facilitate the choice of the
      appropriate process technology.

PMID- 22358648
TI  - The aggregate effect of dopamine genes on dependence symptoms among cocaine
      users: cross-validation of a candidate system scoring approach.
AB  - Genome-wide studies of psychiatric conditions frequently fail to explain a
      substantial proportion of variance, and replication of individual SNP effects is
      rare. We demonstrate a selective scoring approach, in which variants from several
      genes known to directly affect the dopamine system are considered concurrently to
      explain individual differences in cocaine dependence symptoms. 273 SNPs from
      eight dopamine-related genes were tested for association with cocaine dependence
      symptoms in an initial training sample. We identified a four-SNP score that
      accounted for 0.55% of the variance in a separate testing sample (p = 0.037).
      These findings suggest that (1) limiting investigated SNPs to those located in
      genes of theoretical importance improves the chances of identifying replicable
      effects by reducing statistical penalties for multiple testing, and (2)
      considering top-associated SNPs in the aggregate can reveal replicable effects
      that are too small to be identified at the level of individual SNPs.

PMID- 22358650
TI  - Alteration of mammalian cell metabolism by dynamic nutrient feeding.
AB  - The metabolism of hybridoma cells was controlled to reduce metabolic formation in
      fed-batch cultures by dynamically feeding a salt-free nutrient concentrate. For
      this purpose, on-line oxygen uptake rate (OUR) measurement was used to estimate
      the metabolic demand of hybridoma cells and to determine the feeding rate of a
      concentrated solution of salt-free DMEM/F12 medium supplemented with other medium
      components. The ratios among glucose, glutamine and other medium components in
      the feeding nutrient concentrate were adjusted stoichiometrically to provide
      balanced nutrient conditions for cell growth. Through on-line control of the
      feeding rate of the nutrient concentrate, both glucose and glutamine
      concentrations were maintained at low levels of 0.5 and 0.2 mM respectively
      during the growth stage. The concentrations of the other essential amino acids
      were also maintained without large fluctuations. The cell metabolism was altered
      from that observed in batch cultures resulting in a significant reduction of
      lactate, ammonia and alanine production. Compared to a previously reported fed
      batch culture in which only glucose was maintained at a low level and only a
      reduced lactate production was observed, this culture has also reduced the
      production of other metabolites, such as ammonium and alanine. As a result, a
      high viable cell concentration of more than 1.0 * 10(7) cells/mL was achieved and
      sustained over an extended period. The results demonstrate an efficient nutrient
      feeding strategy for controlling cell metabolism to achieve and sustain a high
      viable cell concentration in fed-batch mammalian cell cultures in order to
      enhance the productivity.

PMID- 22358651
TI  - Hybridoma growth in a new generation hollow fibre bioreactor: antibody
      productivity and consistency.
AB  - This paper analyses the performance of MAbMax(TM)/Tricentric(TM), a new
      generation hollow fibre bioreactor, for hybridoma growth and antibody
      productivity, the down stream processing of monoclonal antibody harvests
      throughout the run and the further control of antibody quality consistency.
      Handling and process parameters were optimised using a mouse hybridoma, IgG1(K)
      secretor, and then confirmed with several other hybridomas. Cells were kept at
      optimal viability during an unusually long period of time and a continuously high
      production of antibodies was detected over several months. Foetal bovine serum
      concentration was reduced to 1?% and the effects of weaning of cells from serum
      were monitored in terms of cell metabolism and antibody productivity. Antibody
      harvests collected at regular intervals throughout the run (2 to 12 weeks) were
      purified using affinity chromatography on a recombinant protein A/G matrix and
      then analysed in terms of antigen binding properties, isoelectric forms and
      oligosaccharide structures, in order 1) to control antibody quality consistency
      as a function of time and serum concentration and 2) to compare antibody
      characteristics as a function of culture conditions, in vitro bioreactor
      cultivation versus in vivo mouse ascite cultivation.

PMID- 22358652
TI  - Investigations on oxygen limitations of adherent cells growing on macroporous
      microcarriers.
AB  - Macroporous microcarriers are commonly applied to fixed and fluidized bed
      bioreactors for the cultivation of stringent adherent cells. Several
      investigations showed that these carriers are advantageous in respect to a large
      surface area (Griffiths, 1990; Looby, 1990a).When growing a rC-127 cell line on
      Cytoline 2 (Pharmacia Biotech), no satisfactory product yield could be achieved.
      A possible limitation in the supply of nutrient components was investigated to
      explain these poor results. No significant concentration gradients could be
      detected. Nevertheless, fluorescence staining revealed a decreasing viability,
      particularly inside the macroporous structure. Therefore, oxygen transfer to and
      into the carriers was examined by means of an oxygen microprobe during the entire
      process. Additional mathematical modeling supported these results.The maximum
      penetration depth of oxygen was determined to be 300 MUm. A critical value
      influencing the oxygen uptake rate of the rC-127 cells occured at a dissolved
      oxygen concentration of 8% of air saturation. A significant mass transfer
      resistance within a laminar boundary film at the surface of the carrier could be
      detected. This boundary layer had a depth of 170 MUm. The results showed that
      even a 40% air saturation in the bulk liquid could not provide an efficient
      oxygenation of the surface biofilm during the exponential growth phase.
      Fluorescent staining reveals a poor viability of cells growing inside the carrier
      volume. Thus, oxygen supply limits the growth of rC-127 cells on macroporous
      microcarriers. Poor process performance and low product yield could be explained
      this way.

PMID- 22358653
TI  - Characterization and fed-batch culture of hybridoma overexpressing apoptosis
      suppressing gene bcl-2.
AB  - Mouse hybridoma 2E3 transfected with human bcl-2 gene survived longer with
      increasing expression level of bcl-2 when cultured in DME medium supplemented
      with 9% serum. One of the transfectants, 2E3BCMGbcl-2, overexpressed bcl-2 and
      could maintain viable cell density higher than the initial density for more than
      four days at a low 0.5% serum concentration. In comparison a mock transfectant
      2E3BCMG remained viable for only one day. However, both hybridomas died out
      within a day in serum-free medium. These results suggested that bcl-2 needed a
      small amount of some serum components to suppress apoptosis of the hybridoma.
      Overexpression of bcl-2 also suppressed apoptosis of the hybridoma induced by
      glutamine deprivation. When hybridoma 2E3BCMGbcl-2 was inoculated in DME medium
      supplemented with 9% serum and cultured for 10 d with additional 2% serum feed at
      day 4 of the culture, viable cell density increased 2-fold and antibody produced
      3-fold, in comparison with mock transfected 2E3 cultured in the same manner. The
      mock transfectant with additional feed of serum at day 4 of the culture showed no
      difference in viable cell density and antibody production. These results
      suggested that the mock transfectant committed to apoptosis before day 4 of the
      culture and the additional serum at day 4 could not reverse the commitment.

PMID- 22358655
TI  - Effects of endotoxin on proliferation of human hematopoietic cell precursors.
AB  - In examining the effects of corticosteroids on hematopoiesis in vitro, we
      observed that results were highly dependent on the lot of commercial fetal calf
      serum (FCS) utilized. We hypothesized that this variability correlated with the
      picogram (pg) level of endotoxin contaminating the FCS. Randomly obtained
      commercial lots of FCS contained 0.39 to 187 pg/ml of lipopolysaccharide (LPS).
      Standard FCS concentrations in hematopoietic precursor proliferation assays
      (granulocyte-marcrophage colony forming units [CFU-GM]) resulted in final LPS
      levels as high as 40 pg/ml. LPS (2-5 pg/ml) added to essentially endotoxin-free
      cultures, induced human mononuclear cell release of interleukin (IL)-1, IL-6 and
      granulocyte colony stimulating factor (G-CSF). Lots of FCS induced the release of
      IL-1, IL-6, and G-CSF from human mononuclear cells and the release of these
      factors correlated with the level of contaminating LPS. Human bone marrow CFU-GM
      proliferation, in response to granulocyte-macrophage colony stimulating factor
      (GM-CSF), positively correlated with the level of LPS contaminating the FCS and
      the FCS-induced release of IL-6 from mononuclear cells. CFU-GM proliferation of
      human bone marrow cluster of differentiation (CD) 34+CD14-cells were not affected
      by the presence of endotoxin. These data suggest that LPS at 2-5 pg/ml may induce
      bone marrow accessory cell release of hematopoietic growth factors, thus altering
      proliferative response of hematopoietic precursors and confounding the study of
      exogenously added cytokines to culture systems.

PMID- 22358654
TI  - A tubular segmented-flow bioreactor for the infection of insect cells with
      recombinant baculovirus.
AB  - A continuous process of insect cell (S f9) growth and baculovirus infection is
      tested with the sequential combination of a CSTR and a tubular reactor. A tubular
      infection reactor enables continuous introduction of baculovirus and therefore
      avoids the 'passage effect' observed in two-stage CSTR systems. Moreover, a
      tubular reactor can be used to test cell infection kinetics and the subsequent
      metabolism of infected insect cells. Unlike batch and CSTR culture, cells in a
      horizontally positioned tubular reactor settle due to poor mixing. We have
      overcome this problem by alternately introducing air bubbles and media and by
      maintaining a linear velocity sufficient to keep cells suspended. This article
      addresses the development of the tubular reactor and demonstrates its use as an
      infection system that complements the two-stage CSTR.

PMID- 22358656
TI  - A rapid method for evaluation of cell number and viability by flow cytometry.
AB  - A simple, rapid and reliable method has been developed for assessing the number
      and viability of cells, as well as cell size, in suspension culture by the use of
      flow cytometry. Propidium iodide exclusion is used for viability determination
      and fluorescent beads serve as an internal standard for cell enumeration. The
      main advantages of this method are its ability to handle a large number of
      samples with a high degree of precision and its specificity in detecting viable
      cells quantitatively in a heterogeneous culture of living and dead cells and
      debris. The method shows only a fraction of the variation found in the
      haemacytometer/trypan blue counting method due to its very low operator
      dependence. CHO - Chinese hamster ovary; FCS - Foetal calf serum; FS - Forward
      scatter light; MTT - 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide;
      NCS - newborn calf serum; PBS - Phosphate buffered saline; PI - Propidium iodide;
      SS - Side scatter light.

PMID- 22358657
TI  - Establishment of an abalone digestive gland cell line secreting various
      glycosidases in protein-free culture.
AB  - A cell line designated as ADG was established from an abalone digestive gland
      using ERDF medium supplemented with 8% fetal bovine serum (FBS), 8% abalone
      hemolymph, and high concentrations of NaCl, KCl, MgCl(2), MgSO(4), and CaCl(2).
      ADG cells proliferated better in protein-free medium than in FBS-supplemented
      medium. Among 9 kinds of media examined, ERDF medium was shown to be optimal for
      cell growth. ADG cells secreted 13 different kinds of glycosidases in protein
      free medium: alpha-L-fucosidase, beta-L-fucosidase, alpha-D-galactosidase, beta-D
      galactosidase, N-acetyl-alpha-D-galactosaminidase, N-acetyl-beta-D
      galactosaminidase, alpha-D-glucosidase, beta-D-glucosidase, N-acetyl-alpha-D
      glucosaminidase, N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase, beta-D
      mannosidase, beta-D-xylosidase, and 1-3 xylanase. When ADG cells were cultured in
      Grace's insect cell medium, the activity of some secreted glycosidases increased
      25-fold to 65-fold per cell as compared with control cells cultured in ERDF
      medium. ADG - abalone digestive gland; ERDF - enriched RDF; FBS - fetal bovine
      serum; L-15 - Leibovitz's L-15 media; DME - Dulbecco's modified Eagle medium; F
      12 - nutrient mixture (Ham); LDF - L-15; DME: F-12 = 10 : 7 : 3; MEM - minimum
      essential medium; RPMI - RPMI medium 1640; 199 - media 199; GIC - Grace's insect
      cell medium; pNP -p -nitrophenol.

PMID- 22358658
TI  - Lysozyme stimulates immunoglobulin production by human-human hybridoma and human
      peripheral blood lymphocytes.
AB  - Lysozyme [EC 3.2.1.17] derived from hen egg white stimulated immunoglobulin
      production by human-human hybridoma, HB4C5 cells producing human lung cancer
      specific monoclonal IgM. IgM production by HB4C5 cells was enhanced more than 13
      fold by the addition of lysozyme at 380 MUg/ml in a serum-free medium. The
      immunoglobulin production stimulating effect of lysozyme was observed immediately
      after inoculation and maintained for 5 days. Lysozyme enhanced immunoglobulin
      production by the hybridoma line without growth promotion. This enzyme also
      accelerated IgM and IgG production of human peripheral blood lymphocytes 5.3-fold
      and 2.3-fold, respectively. These results suggest that lysozyme stimulates
      immunoglobuling production of not only specific hybridoma line, but also non
      specific immunoglobulin producers. However, although the enzymatic activity of
      lysozyme was almost lost by heat-treatment at 100  degrees C for 30 min, the IPSF
      activity was retained. This fact suggests that IPSF activity of lysozyme does not
      come from its enzymatic activity or reaction products. All these findings clearly
      indicate that lysozyme has a novel function as an immunoglobulin production
      stimulating factor. GAPDH - glyceraldehyde-3-phosphate dehydrogenase; Ig -
      immunoglobulin; IPSF - immunoglobulin production stimulating factor; PBL -
      peripheral blood lymphocytes; HPLC - high-performance liquid chromatography.

PMID- 22358659
TI  - Introduction.

PMID- 22358660
TI  - Evaluation of a simple protein free medium that supports high levels of
      monoclonal antibody production.
AB  - A simple protein free medium was formulated and tested in suspension culture
      using three hybridoma cell lines. The medium, referred to as CDSS (Chemically
      Defined Serum Substitutes), consisted of the basal medium DMEM:Ham F12, 1:1, with
      HEPES (D12H), plus pluronic F68, trace elements, ferric citrate, ascorbic acid,
      and ethanolamine. No protein or lipid components were added. All three cell lines
      were weaned off serum using CDSS and a commercially available protein free medium
      PFHM-II. Data shown here indicated that normally cells took 1-7 weeks to wean off
      serum and an additional 2-7 weeks to adapt to suspension culture. After
      adaptation the cells were able to grow well in suspension culture using both
      protein free media and in the main performed better than serum containing
      controls. The stability of the three hybridoma cells for antibody production
      following freeze/thaw procedures and long term subculturing was also tested. All
      three lines were frozen using our protein free CDSS medium (containing 0.75%
      bovine serum albumin and 10% dimethyl sulfoxide) in liquid nitrogen for up to one
      year. Cells thawed from these stocks recovered well and were able to maintain
      good growth and antibody production characteristics. One line was shown to grow
      using our protein free CDSS medium in suspension culture for 12 weeks without
      loss of antibody productivity.

PMID- 22358661
TI  - Amino acid metabolism during batch culture of a murine hybridoma, AFP-27.
AB  - This paper presents batch culture data of the murine hybridoma, AFP-27, cultured
      in conventional basal media and in a nutrient-rich modified version. Expression
      of antibody was fivefold higher in the enriched formulation, with significant
      product secretion in the decline phase. Cultures were initiated at conventional
      inculation densities (1 ~ 2 * 10(5) viable cells ml(-1)) and high inoculation
      densities (1.5 ~ 1.7 * 10(6) viable cells ml(-1)). Amino acid levels have been
      reported for all cultures, with apparent differences described. Relative levels
      of intracellular amino acids are also reported, with significant accumulation of
      proline, glycine and alanine. The results have significance in the design of
      enriched media which are clearly beneficial for commercial production of
      antibodies from hybridomas.

PMID- 22358662
TI  - Carbohydrate and amino acid metabolism during batch culture of a human
      lymphoblastoid cell line, BTSN6.
AB  - This work presents data on the carbohydrate and amino acid metabolism of a
      lymphoblastoid cell line producing an IgG1 antibody. In static culture, it was
      observed that lactate levels were significantly lowered when the cells were
      cultured on galactose as a carbon source. The use of carbohydrate substitution
      may be useful in lowering lactate levels, if it is established that this
      component is toxic to the cells. In addition, carbohydrate substitution may be
      used to modify glycosylation patterns and hence pharmacokinetic properties of
      glycoproteins.The amino acids glutamine and tryptophan were shown to be limiting
      in batch culture on this medium (DR, a 1:1 mixture of DMEM and RPMI, with 4mM
      glutamine). Amino acids produced included alanine, proline and glutamate. Serine
      was consumed to exhaustion, which was followed by a depletion of extracellular
      glycine. Amino acid metabolism, specific antibody productivity and specific
      growth rate were shown to be functions of the inoculation density in stirred
      flask culture. The results have implications for the design of media for both low
      and high density antibody manufacture by these cell lines.

PMID- 22358663
TI  - Biosynthesis of protein products by animal cells. Are growth and non-growth
      associated concepts valid or useful?
AB  - The application of simple growth and non-growth associated concepts from
      microbial systems describing substrate uptake and production formation is
      considered unlikely to assist in the understanding of antibody formation and,
      hence, in maximising antibody yield. Such concepts have many significant
      limitations - notably, their strict application only to products of catabolic
      pathways and their inability to include metabolisms which either have multiple
      catabolic pathways (eg, fermentation and respiration in yeast and animal cells)
      or in which the major product of interest is predominantly anabolic in nature
      (eg. amino acid production in bacteria and antibody formation in animal cells).
      In addition, products which undergo an assembly and secretion process or a
      secretion process which allows intracellular pools of product to exist are also
      not well described by such simple relationships. In this work, inadequacies in
      the current approach to the study of the kinetics of growth of hybridoma cells
      and antibody production are described and the examples of growth ofSaccharomyces
      cerevisiae andCandida utilis, amino acid production by bacteria and antibody
      production by animal cells are used to illustrate these limitations. Having
      identified these limitations, suggestions are made as to how studies might be
      undertaken to assist our future understanding of the process of antibody
      manufacture and, subsequently, maximizing antibody yield. The process of
      characterising the metabolism of anabolic products is subject to detailed
      computer simulation of the pathways involved. It is argued that such approaches
      will assist us in understanding more fully the nature of biosynthetic products
      and how they integrate with the major energy producing pathways of the cell and
      the cell cycle. This will assist in maximising the yield of such products.

PMID- 22358664
TI  - Structured modelling of animal cells.
AB  - Recent advances in computer technology have promoted the design and use of
      detailed, computer-based models for biological systems. For many non-biological
      systems, the complexity of such simulations may be considered inappropriate and
      unwieldy, but in biological systems, and more specifically in animal cell
      culture, this level of complexity simply mimics what is only beginning to be
      understood about metabolic processs. With this in mind, we contend that complex,
      structured models are vital tools in the investigation of fundamental biological
      processes. An example of such a simulation, which describes the commercial
      production of therapeutic proteins by animal cell cultures, is considered.

PMID- 22358665
TI  - The kinetics of baculovirus adsorption to insect cells in suspension culture.
AB  - The influence of various culture parameters on the attachment of a recombinant
      baculovirus to suspended insect cells was examined under normal culture
      conditions. These parameters included cell density, multiplicity of infection,
      and composition of the cell growth medium. It was found that the fractional rate
      of virus attachment was independent of the multiplicity of infection but
      dependent on the cell density. A first order mathematical model was used to
      simulate the adsorption kinetics and predict the efficiency of virus attachment
      under the various culture conditions. This calculated efficiency of virus
      attachment was observed to decrease at high cell densities, which was attributed
      to cell clumping. It was also observed that virus attachment was more efficient
      in Sf900II serum free medium than it was in IPL-41 serum-supplemented medium.
      This effect was attributed to the protein in serum which may coat the cells and
      so inhibit adsorption. A general discussion relating the observations made in
      these experiments to the kinetics of recombinant baculovirus adsorption to
      suspended insect cells is presented.

PMID- 22358666
TI  - Biological activity and metabolic clearance of recombinant human follicle
      stimulating hormone produced in Sp2/0 myeloma cells.
AB  - Human follicle stimulating hormone is a pituitary glycoprotein that is essential
      for the maintenance of ovarian follicle development and testicular
      spermatogenesis. Like other members of the glycoprotein hormone family, it
      contains a common a subunit and a hormone specificbeta subunit. Each subunit
      contains two glycosylation sites. The specific structures of the oligosaccharides
      of human follicle stimulating hormone have been shown to influence both thein
      vitro andin vivo bioactivity. Since the carbohydrate structure of a protein
      reflects the glycosylation apparatus of the host cells in which the protein is
      expressed, we examined the isoform profiles,in vitro bioactivity and metabolic
      clearance of a preparation of purified recombinant human follicle stimulating
      hormone derived from a stable, transfected Sp2/0 myeloma cell line, and pituitary
      human follicle stimulating hormone. Isoelectric focussing and chromatofocussing
      studies of human follicle stimulating hormone preparations both showed a more
      basic isoform profile for the recombinant human follicle stimulating hormone
      compared to that of pituitary human follicle stimulating hormone. The recombinant
      human follicle stimulating hormone had a significantly higher radioreceptor
      activity compared to that of pituitary human follicle stimulating hormone,
      consistent with a greaterin vitro potency. Pharmacokinetic studies in rats
      indicated a similar terminal half life (124 min) to that of the pituitary human
      follicle stimulating hormone (119 min). Preliminary carbohydrate analysis showed
      recombinant human follicle stimulating hormone to contain high mannose and/or
      hybrid type, in addition to complex type carbohydrate chains, terminating with
      bothalpha2,3 andalpha2,6 linked sialic acids. These results demonstrate that
      recombinant human follicle stimulating hormone made in the Sp2/0 myeloma cells is
      sialylated, has a more basic isoform profile, and has a greaterin vitro
      biological potency compared to those of the pituitary human follicle stimulating
      hormone.

PMID- 22358667
TI  - Ligation of the lymphocyte homing receptor CD44 triggers T-helper and cytolytic
      functions of human T cells.
AB  - We show that antibodies to the CD44 molecule trigger proliferation of human
      CD3+/CD4+ T-cell clones. Such effect is IL2-dependent, as shown by IL2 production
      induced by anti-CD44 mAb and by inhibition of cell proliferation in the presence
      of anti-IL2 antibodies or cyclosporin A (CsA). Moreover, anti-CD44 mAb triggered
      human cytolytic CD4+ and CD8+ TCR alpha/beta+ clones, and Vdelta1 or Vdelta2 TCR
      Y/delta+ clones to lyse Fc-gamma-R+ P815 cells and to release granule trypsin
      like esterase enzymes. Anti-CD44 mAb-triggered proliferation and cytotoxicity
      were blocked by the PTK-inhibitor, genestein. In addition, ligation of the CD44
      molecule induced tyrosine phosphorylation of proteins identical, by molecular
      weight, to those phosphorylated following anti-CD3 mAb-stimulation. Notably, anti
      CD44 mAb does not induce tyrosine phosphorylation of a 21 kD protein (the
      phosphorylated zeta chain of the TcR molecular complex) typically observed upon
      anti-CD3 mAb stimulation.

PMID- 22358668
TI  - Study on the synthesis of complement components by human renal mesangial cells in
      culture. Assessment of the effect of cytokines.
AB  - Renal mesangial cell (MC) cultures are easily established and widely used. MC
      produce some complement (C) regulatory proteins. We studied whether MC synthesize
      C components (C3, C5, C8). MC cultures were established from normal portions of
      cortices of nephrectomies for renal cancer. After growing to near-confluence in
      RPMI/17% FBS and resting for 24 h in RPMI/0.5% FBS, MC were stimulated up to 72 h
      with IL-1beta or IL-6 (10, 100, 1000 U/ml). Neither C5 nor C8 were detected by
      ELISA. While C3 was present in supernatant under basal conditions (15.5-107.6
      ng/10(6) cells/24h) in different MC lines. IL-1beta up-regulated the synthesis by
      2.4-4.5 folds, whereas IL-6 did not show any effect. C3 synthetic rate was 1,76
      ng/h/10(6) cells under IL-1 stimulation versus basal rate of 0,37 ng/h/10(6)
      cells. MC production of C3, especially induced by IL-1 may have pathogenetic
      relevance in glomerulonephritis.

PMID- 22358669
TI  - Genotypic and phenotypic changes of BHK-21 cells grown in suspension cultures.
AB  - The propagation of foot-and-mouth disease virus on BHK-21 suspension cells,
      although economically convenient, may yield a scarcely immunizing antigen.
      Helpful insights were obtained by investigating a few genotypic and phenotypic
      features of the cell cultures. The appearance of polyploid populations, higher
      cell concentrations at the end of culturing, the progressive reduction of
      spreading on surfaces and an abnormal expression of the alpha5beta1 integrin were
      found to be correlated with the number of passages in suspension culture. The
      observed modifications in the normal course of the cell-cycle and in the
      expression of some surface proteins point at a possible mechanism of virus
      damages arising from defective cellular functions.

PMID- 22358670
TI  - Identification of a new surface molecule involved in the mechanism of cell to
      cell adhesion between human NK and tumor target cells.

PMID- 22358671
TI  - Cell-matrix interactions in cultured dermal fibroblasts from patients with an
      inherited connective-tissue disorder.
AB  - Indirect-immunofluorescence studies were performed on cultured dermal fibroblasts
      from patients with Pseudoxanthoma Elasticum (PXE), an inherited connective-tissue
      disorder the pathogenesis of which is still unknown. Apparent abnormalities of
      cytoskeletal structures were revealed by using phalloidin and specific antibodies
      to alfa-smooth muscle actin and to vimentin. Altered expression of intergrin
      receptors for different extracellular matrix components seems to be present in
      the pathological cells as preliminary data suggest by using antibodies against
      alfa subunits of integrins. This study was designed to test the presence of
      abnormal cell-matrix interactions responsible for the clinical features and
      involved in the pathogenesis of the PXE disease.

PMID- 22358672
TI  - Cerebellar neurones: Differentiation and modulation of sensitivity to excitotoxic
      treatment.
AB  - The neurite outgrowth and adhesion complex (NOAC), isolated from rabbit sera has
      been dissociated in its major components by reverse-phase chromatography in HPLC
      by using a C(18) column. SDS-PAGE analisys of the active fractions revealed the
      presence of three major bands of approximately 100, 70 and 50 kDa. Studies on the
      biological activity of NOAC were carried out on rat cerebellar granule cells.
      NOAC-cultured cells exhibit a marked resistance to excitotoxic stimuli carried by
      glutamate.

PMID- 22358673
TI  - Events associated with EGF - Induced DNA synthesis in primary cultures of rat
      hepatocytes.

PMID- 22358674
TI  - Refinement of a thyroid cultured cell system used in clinically relevant
      bioassays.
AB  - Thyroid cultured cells are now used worldwide in clinical bioassays of TSH and of
      thyroid autoantibodies. Having originally developed the thyroid cell cultures
      (Ambesi-Impiombato et al. 1980) from rat glands in our laboratory, we now aim to
      improve the system, moving in two directions: a) TSH-independent mutants have
      been produced and characterized, which can be used in clinical bioassays without
      "starvation" from the hormone. b) Human cultures have been attempted using our
      experience with rat cells, as well as innovative strategies. Preliminary results
      now indicate that human normal differentiated cells may be available for clinical
      studies in vitro, when species-specific differences may be critical.

PMID- 22358675
TI  - State of the foreign gene and of the genome in transgenic rice (Oryza sativa L.).
AB  - PCR with random primers (RAPD analysis) performed on the DNA of embryogenic and
      non-embryogenic suspension cultured rice and of transformed rice plants allows
      the evaluation of the extent of DNA changes in the different biological
      materials. This is thus suggested as a convenient approach, in combination with
      restriction analysis and Southerns blotting, to evaluate the integrity of the
      foreign gene, the stability of the insertion site and the stability of the whole
      genome.

PMID- 22358676
TI  - Use of established hepatoma cell lines in biotoxicology.
AB  - CONCLUSIONS: In conclusion, hepatoma cell lines displaying multiple combinations
      of bioactivating and inactivating enzymes, even if do not seem to represent liver
      specific bio-indicators of toxicity, are a polyvalent liver system, suitable to
      evaluate particular end-points.

PMID- 22358677
TI  - The cell line data base and the new catalogue: Detailed information on 2650 human
      and animal cell lines.
AB  - The Cell Line Data Base (CLDB), set up within the Interlab Project, is a
      relational database containing data on 2650 Human and animal cell lines which are
      available in labs and cell banks all over Europe. The second edition of the
      catalogue, directly generated from the database, has been produced, and will be
      published in the first months of 1993. Furthermore, the electronic catalogue is
      available for IBM-compatible personal computers and the version for MacIntosh is
      under preparation.

PMID- 22358678
TI  - Cellfile: A cell line databank for specialized catalogs.

PMID- 22358679
TI  - Cell cultures in the biocompatibility study of synthetic materials.
AB  - In vitro cytotoxicity (Neutral Red uptake, Kenacid Blue and MTT) and
      cytocompatibility (cell adhesion and proliferation) tests were applied to the
      biocompatibility study of a series of poly(ester-ether-ester) block copolymers of
      potential interest as biomaterials. Our results indicate that the copolymer
      extracts after 72 hours incubation with a 3T3 mouse fibroblast cell line do not
      induce significant toxic effects. Furthermore, human umbilical vein endothelial
      cells seeded on thin copolymer films show a normal pattern of growth. We conclude
      that thein vitro tests used are a valid instrument to evaluate the potential
      toxic action of synthetic materials on different cell compartments and that the
      tested materials seem to be promising for future applications in the field of
      biomedical devices.

PMID- 22358680
TI  - Interferon-gamma-induced differentiation of human neuroblastoma cells increases
      cellular uptake and halflife of metaiodobenzylguanidine.
AB  - Iodine labeled metaiodobenzylguanidine (MIBG) is a radiopharmaceutical employed
      for both diagnosis and metabolic radiotherapy of neuroblastoma (NB). Resistance
      to the radiotherapeutic effects of MIBG is common, due to lack of MIBG
      accumulation by NB cells. MIBG enters competent cells via the noradrenaline
      transporter; this function requires a relative cellular maturation and is missing
      in most NB cell lines. In vitro differentiation of NB cells can be achieved with
      gamma-interferon (gamma-IFN) and other agents. We have verified that gamma-IFN
      induced differentiation of NB cells is specifically associated with an increase
      in their ability to incorporate MIBG. This phenomenon is due to enhancement of
      MIBG transporter activity, according to pharmacological sensitivity and
      semiquantitative PCR-based analysis of specific MIBG transporter mRNA. New
      therapeutic strategies, based on both differentiation therapy and targeted
      radiotherapy of NB can so be devised.

PMID- 22358681
TI  - Effect of atherogenic lipoproteins on PAI-1 synthesis by endothelial cells.
AB  - Cultured human umbilical vein endothelial cells (EC) exposed to native and
      acetylated low density lipoproteins (LDL and acetyl-LDL) show an increased
      synthesis of PAI-1. Confluent EC monolayers were incubated for 16-18 hours in
      medium 199 with or without different concentrations of LDL and acetyl-LDL and PAI
      1 antigen levels were measured in conditioned medium. LDL and acetyl-LDL
      increased the release of PAI-1 by EC in a concentration-dependent manner. The
      effect was specific for PAI-1 because tissue type plasminogen activator (t-PA)
      and expression of procoagulant activity were not affected by either lipoprotein.
      The observation that native and acetyl-LDL, which are known to interact with
      different receptors on EC, exert the same stimulatory effect on PAI-1 release
      rules out the possibility of an involvement of the LDL receptor in mediating this
      effect. Experiments carried out incubating native LDL in the presence of a
      monoclonal antibody against LDL receptor and using binding-defective LDL with a
      reduced affinity for the LDL receptor (~50% with respect to normal LDL) further
      excluded an involvement of the classical LDL receptor in mediating the effect of
      the lipoproteins on PAI-1 synthesis by EC.

PMID- 22358682
TI  - Mab labelled liposomes as selective vehicles for drugs in H.I.V. infected cells.
AB  - CONCLUSION: Being able to carry zidovudine (AZT) at known concentrations into
      CD4+/CD38+ and CD14+ cells permits:  - to reduce the drug dosage and to increase
      the interval for administration (until 1 dose I.V. every week);   - to modulate
      the drug concentration into the CD4+/CD38 an CD14+ cells in relation to the "in
      vitro" determined HIV sensitiveness;   - to eliminate haematological, medullary
      and general toxicity;   - to be able to treat severely hill patients.   Further
      studies are necessary in order to:  - To find out the better phase to start the
      therapy;   - To use several drugs with different mechanisms of action in order to
      slow down as much as possible the presence of resistant viral strains.   - As for
      other drugs which are beginning to be used with artificial vehicles, futher
      studies are required to improve the selectivity and safety of LIPOAZT for the
      target cells including macrophages.

PMID- 22358683
TI  - Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis
      in human hepatoma cell line Hep G2.
AB  - The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism
      was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake
      and degradation of(125)I-LDL in a dose-dependent manner. The drug inhibited
      cholesterol synthesis and esterification without affecting cellular cholesterol
      content and bile acid synthesis; cholesterol efflux was slightly increased. These
      results show that the inhibition of cholesterol synthesis together with the
      enhanced expression of LDL receptors may partially explain the
      hypocholesterolemic activity of compound AR12456.

PMID- 22358684
TI  - Trapidil, a PDGF-receptor antagonist, inhibits human mesangial cell (HMC)
      proliferation.

PMID- 22358685
TI  - Leukemia-inhibitory factor and neuroblastoma cell lines: Study on the expression
      of this citokine and on its efficacy as differentiating agent.

PMID- 22358686
TI  - Cytosine arabinoside modulates endothelial cell proliferation in "in vitro"
      angiogenesis.

PMID- 22358687
TI  - Effectiveness of the combination DDP-AR in inducing cytotoxic effect on a human
      glioblastoma cell line.

PMID- 22358688
TI  - Lipid peroxidation in hepatoma cell lines and their sensitivity to 4
      hydroxynonenal.

PMID- 22358689
TI  - Cytotoxic effects produced on a continuous cell line by the nematocyst venom
      ofAnemonia sulcata (Cnidaria: Anthozoa). I.

PMID- 22358690
TI  - Measurement of reacting oxigen species produced by human polimorphonuclears or
      bovine alveolar macrophages exposed to clay mineral, advised to replace asbestos.

PMID- 22358691
TI  - Spontaneous transformation and immortalization of peritoneal macrophages of human
      origin.

PMID- 22358692
TI  - Vimentine and cytokeratines expression in LoVo cell clones intrinsically
      resistant to doxorubicin.

PMID- 22358693
TI  - Cell injury and death induced by free radicals in HIV-susceptible cells.

PMID- 22358694
TI  - An immunoclone database for the European scientific community.

PMID- 22358695
TI  - Monitoring of multidrug resistence in a human leukemic cell line by cytogenetic
      and molecular analysis.

PMID- 22358696
TI  - Gamma enolase expression as early marker of neuronal differentiation of murine
      neuroblastoma cells N-115.
AB  - In this study we determined the levels of gamma enolase mRNA in mouse
      neuroblastoma cell line N-115 at early period of induction of differentiation by
      serum withdrawal. The expression of gamma enolase was examined by Northern blot
      analysis of total RNA extracted from cells induced for different lengths of time.
      We found a 3-fold increase in the level of gamma enolase mRNA after 24 hours of
      induction of differentiation and higher levels were detected in cells induced for
      longer time, reaching a 10-fold increase after four days.

PMID- 22358697
TI  - Callogenesis, somatic embryogenesis and active principles from explants
      ofAesculus hippocastanum L.

PMID- 22358698
TI  - Thein utero initiation with DMN alters the complement of cytosolic glutathione S
      transferases and the phenobarbital-induced expression ofc-jun andc-myc oncogenes
      in primary neonatal rat hepatocytes.
AB  - As revealed by a novelin utero-in vitro hepatocarcinogenesis model, a single
      exposure to dimethylnitrosamine (DMN) elicited in postnatal (and fetal) primary
      rat hepatocytes (i) immunocytochemically detectable, widespread increases in
      their complement of thealpha, mu and especiallypi classes of cytosolic
      glutathione S-transferases (GST's); and (ii) changed patterns (with respect to
      controls) of the phenobarbital (PB)-evoked increases in steady state levels ofc
      jun andc-myc mRNA's. These results indicate that DMN causes both transient
      cytotoxic effects and a broad, permanent initiation in fetal proliferating
      hepatocytes.

PMID- 22358699
TI  - Use of V79-derived cell lines expressing cytochrome P-450 activity in the study
      of genotoxicity of anthraquinones.

PMID- 22358700
TI  - Use of cell cultures, nuclear and radioanalytical techniques for
      metallotoxicological studies at the JRC-Ispra.
AB  - This paper reviews the JRC-Ispra research activity on toxicological studies
      related to the environmental and occupational exposure of trace metals, as
      carried out by a combination of cell culture methodologies with nuclear and
      radioanalytical techniques.Applications concern the setting of uptake-effect
      relationships and the study of the mechanisms of toxicity of specific metals (Al,
      As, Cd, Co, Cr, Mo, Se, V), as well as the establishment of ranking of metal
      toxicity by carrying out systematic studies (screening tests).

PMID- 22358701
TI  - Tri-iodothyronine effects on Sertoli cell protein turnover in the prepubertal
      pig.
AB  - The direct effect of Tri-iodothyronine (T(3): 0.1-100 nM) on protein turnover was
      studied using primary cultures of Sertoli cells isolated from immature piglet
      testis. The results demonstrate that T(3) significantly increases protein
      synthesis without altering the protein degradation rate. These data and previous
      ones, showing the presence of specific T(3) receptors in Sertoli cell nuclei,
      indicate that T(3) plays a fundamental role in the early regulation of porcine
      Sertoli cell growth and maturation.

PMID- 22358702
TI  - Recent progresses on long-term hepatocyte primary cultures: Importance of cell
      microenvironments.

PMID- 22358703
TI  - Receptor-mediated oligodeoxynucleotides delivery by estradiol and folic acid
      polylysine conjugates.
AB  - The lack of efficient and specific delivery to target cells still limits the
      potential application of antisense oligodeoxynucleotides as therapeutic agents in
      cancer disease. We have covalently linked a polylysine chain (10,000-20,000 mW)
      to compounds as folic acid, retinoic acid, transferrin, insulin and estradiol, to
      deliver c-myb antisense oligonucleotide into tumor cells. Using these complexes
      as carriers for the oligodeoxynucleotides can be achieved an increase in their
      uptake into target cells through a natural endocytosis pathway.

PMID- 22358704
TI  - A novel way to get out of the cell.

PMID- 22358705
TI  - The alpha6beta1 integrin is a laminin receptor for developing retinal neurons.
AB  - Cultured embryionic day 6 (E6) retinal neurons respond to laminin by making use
      of integrin receptors. We have recently shown that the laminin binding integrin
      receptor alpha6beta1 is expressed in the chick retina on both retinal ganglion
      cells and other retinal neurons. Antibodies raised against a fusion protein
      containing a large fragment of the extracellular portion of the chick alpha6
      integrin subunit dramatically inhibit the interactions between E6 retinal neurons
      and laminin. These data show that alpha6beta1 functions as a laminin receptor in
      these cells. In previous work we have also shown that the levels of the mRNA for
      alpha6 decreases dramatically in retinal ganglion cells between E6 and E12. Data
      presented in this paper show that the decrease in alpha6 mRNA is not prevented by
      ablation of the optic tectum, indicating that contact with the target is not a
      major cause for this decrease.

PMID- 22358706
TI  - Intracellular targeting of the photoprotein aequorin: A new approach for
      measuring, in living cells, Ca(2+) concentrations in defined cellular
      compartments.
AB  - We here present a novel method, based on the targeting of the photoprotein
      aequorin, for measuring the concentration of Ca(2+) ions in defined cellular
      compartments of intact cells. In this contribution we will discuss the
      application to mitochondria. A chimaeric cDNA was constructed by fusing in frame
      the aequorin cDNA with that for a mitochondrial protein. The cDNA encoded a
      "mitochondrially-targeted" aequorin, composed of a typical mitochondrial
      targeting signal at the N-terminus and the photoprotein at the C-terminus. The
      cDNA, inserted in the expression vector pMT2, was co-transfected into bovine
      endothelial and HeLa cells together with the selectable plasmid pSV2-neo and
      stable transfectants, selected for high aequorin production, were analyzed. In
      subcellular fractionations, aequorin was shown to be localized in mitochondria;
      in intact cells, the first direct measurement of mitochondrial free Ca(2+),
      [Ca(2+)](m), were obtained, which showed that [Ca(2+)](m) is low at rest (<0.5
      MUM), but rapidly increases to the micromolar range upon cell stimulation [1].
      These data indicate that mitochondria "sense" very accurately the cytosolic
      Ca(2+) concentration ([Ca(2+)](i)), and after cell stimulation [Ca(2+)](m) rises
      to values capable of activating the Ca(2+)-sensitive mitochondrial
      dehydrogenases.

PMID- 22358707
TI  - Regulation of endocytosis by the small GTP-ase Rab5.
AB  - Rab5 is a small GTPase associated with the plasma membrane and the early
      endosomes. Expression of wild type rab5 and a mutant protein defective in GTP
      binding in BHK cells led to alterations in the rate of endocytosis and in the
      morphology of endocytic organelles. The results obtained suggest that rab5 is a
      rate limiting GTPase that regulate the kinetics of both lateral fusion of early
      endosomes and fusion of plasma membrane-derived endocytic vesicles with early
      endosomes.

PMID- 22358708
TI  - Production and secretion of interleukin 1 receptor antagonist in monocytes and
      keratinocytes.
AB  - IL-1 receptor antagonist (IL-1ra) is a newly described member of the IL-1 family,
      isolated from supernatants of Ig stimulated monocytes, that binds competitively
      to IL-1 receptors without stimulating target cells (1-3). Also epithelial cells
      produce IL-1ra in a form which lacks a secretory signal sequence (4).Here we have
      compared the biosynthesis and secretion of IL-1ra in monocytes and keratinocytes.
      Our data show that monocytes produce two molecular forms of IL-1ra, of 18 Kd and
      23 Kd respectively, which differ in the degree of glycosylation. Both forms are
      secreted via the "classical" endoplasmic reticulum (ER)-Golgi secretory pathway.
      By contrast keratinocytes produce IL-1ra in a molecular form of 20 Kd, which is
      not N-glycosylated: 20 Kd IL-1ra is detectable in supernatants of keratinocytes,
      although in small amounts. The presence of IL-1ra in keratinocytes cultures
      fluids is not inhibited by Brefeldin A (BFA), suggesting a possible secretion
      through the leaderless secretory pathway.

PMID- 22358709
TI  - Oxidative stress and transferrin receptor recycling.
AB  - Perturbation of the oxidative balance in biological systems plays an important
      role in numerous pathological states as well as in many physiological processes
      such as receptor activity. In order to evaluate if oxidative stress induced by
      menadione influences membrane receptor processes, a study was conducted on the
      transferrin receptor. Consequently, biochemical, biophysical and ultrastructural
      studies were carried out on different cell lines. The results obtained seem to
      indicate that oxidative stress is able of inducing a rapid and specific down
      modulation of membrane transferrin receptor due to a block of receptor recycling
      on the cell surface without affecting binding affinity.

PMID- 22358710
TI  - Interaction ofEscherichia coli cytotoxic necrotizing factor type 1 (CNF1) with
      cultured cells.
AB  - The cytotoxic necrotizing factor type 1 (CNF1) fromE. coli causes necrosis in
      rabbit skin and multinucleation in cultured cells. Cells exposed to CNF1 were
      characterized by changes in actin organization, mainly consisting in the presence
      of well-developed stress fibers and membrane ruffles. The interaction of CNF1
      with the cell cytoskeleton probably promotes the cell spreading and interferes
      with the cytokinesis, leading to the formation of giant multinucleated cells.

PMID- 22358711
TI  - Gingival fibroblasts "in vitro" and Down's Syndrome.
AB  - Gingival fibroblast cultures from four patients with Down's Syndrome (DS) and
      periodontal disease were compared with four in vitro age-matched fibroblast
      cultures of handicapped subjects (ND) also affected by periodontitis. The extra
      copy of cromosome 21 could alter growth regulation and biochemical mechanisms, so
      we examined quantitatively some DS phenotypical aspects to detect possible
      differences from those of controls. The growth properties of gingival fibroblast
      cultures from DS patients were more elevated than their ND age-matched controls.
      There were no differences in plasma membrane polarization and in neutral
      endopeptidase activity. The succinate-cytochrome C reductase activity decreases
      in DS fibroblasts compared with ND. Our results outline the difficulties to
      inusing fibroblast cultures as an in vitro system to study premature ageing
      Down's Syndrome.

PMID- 22358712
TI  - Human hepatocyte primary cultures in toxicity assessment.
AB  - Forty-two compounds of various chemical families were tested for their
      cytotoxicity and for their ability to induce DNA fragmentation and DNA repair
      synthesis in primary cultures of hepatocytes obtained from 74 human donors, and a
      comparison was carried out with data provided in the same experimental conditions
      by rat hepatocytes. The results indicate that for the majority of chemicals the
      intraspecies variability was greater than the average interspecies difference.
      Some chemicals, however, produced quite different effects in the hepatocytes of
      the two species, and this suggests that rat hepatocytes might be sometimes
      inappropriate predictor of the human response.

PMID- 22358713
TI  - Cytoskeletal modifications induced by 4-hydroxynonenal.
AB  - The antiproliferative action of 4-hydroxynonenal (HNE) could be related to an
      interaction with cytoskeletal structures. In this paper the effects exerted by
      HNE on microtubules and on microfilaments are examined by immunofluorescence. HNE
      alters cell morphology causing both the depolymerization of the microtubular
      structures and the dissolution of the stress-fibres. Taxol protects microtubules,
      preventing the depolymerizing effect of the aldehyde. The action of HNE could be
      attributed to its affinity for sulphydryl groups, which are essential in
      maintaining tubulin and actin both in the polymerized form.

PMID- 22358714
TI  - Prediction of protein folding pathways: Bovine pancreatic trypsin inhibitor.
AB  - A previous theory for the prediction of protein folding pathways [1] is applied
      to bovine pancreatic trypsin inhibitor and the resulting sequence of folding
      events shown to corroborate well with available experimental data.

PMID- 22358715
TI  - Confocal microscopy and cellular bioinformatics.
AB  - An exhaustive description of most biological data requires, besides a set of
      analytic information, an eidetic representation of the data itself. In this
      paper, two topics are presented. The first one is confocal microscopy, an
      advanced technique to produce multidimensional cellular and subcellular
      structures images. The second one is a software application, named BIOCELL, based
      on a relational database management system, developed to provide the biologist
      with an integrated tool to handle simultaneously cell biology linguistic and
      eidetic information.

PMID- 22358716
TI  - Engineering of animal and human red blood cells: State of the art.

PMID- 22358717
TI  - Biological paradigms of molecular electronics.
AB  - Biological processors of information are shown to be paradigms of Molecular
      Electronics, suggesting the main features of systems for intelligent information
      processing at molecular level.

PMID- 22358718
TI  - Images of cultured neurons: Morphological and functional information.
AB  - The in vitro culture of neuronal cells is a useful tool for studying, in a
      controlled way, neurobiological and neuropharmacological phenomena. A first step
      towards the understanding of these phenomena is described. Effects of simulated
      excitatory/inhibitory synapses, artificially positioned along the digitized image
      of neural arborizations, are presented.

PMID- 22358719
TI  - Interpretation of gascromatographic data via artificial neural networks for the
      classification of marine bacteria.
AB  - We propose a new method for classification of marine bacteria. This method uses
      gaschromatograms, which contain information of fatty acid percentage contents of
      the fresh isolate. For the interpretation of these gaschromatograms we use a
      surpervisioned artificial neural network. We present a preliminary study on this
      matter, whose first results show good convergence and classification features.

PMID- 22358720
TI  - Early detection of cell metabolism with a silicon microsensor.
AB  - A silicon microsensor (ISFET - Ion Sensitive Field Effect Transistor) has been
      used to detect the metabolism of a cell population cultured on a coverslip and
      positioned close to the sensor surface. The system output is analyzed as a
      function of cell density.

PMID- 22358721
TI  - Rat hepatocytes in single cell suspension: A still suitable system for lipid
      peroxidation studies.
AB  - The investigation of toxic compounds which need a previous metabolic activation
      often gets advantage by the employment of cell suspensions, in most of the cases
      rat hepatocytes. In particular, this model system allows the characterization of
      lipid peroxidation kinetics, the evaluation of its pathogenetic role in the
      induction of cell death and the analysis of the interaction among different
      prooxidant compounds in bringing about both oxidative damage and cytolysis.

PMID- 22358722
TI  - Cell adhesion molecules duringXenopus myogenesis.
AB  - Muscle development is characterized by several cell-recognition events such as
      the fusion of primary and secondary myoblasts and synaptogenesis. Cell surface
      adhesion receptors are probably playing an important role in determining the
      correct evolution of these processes. In this paper we examine the expression of
      three cell adhesion molecules, N-CAM, N-cadherin and EP-cadherin, duringXenopus
      larval muscle development. Their differential distribution suggests a specific
      role for each of these molecules during myogenesis. N-CAM might control the
      fusion of primary myoblasts as its expression is particularly high in these cells
      and decreases sharply in myotubes. EP-cadherin is present both in differentiated
      myotubes and myoblasts and could be involved in secondary myoblast fusion. While
      N-cadherin appears only much later during muscle differentiation.

PMID- 22358723
TI  - Functions and expression of liver N-CAM.
AB  - CONCLUSIONS: In conclusion we have shown that: (a) liver N-CAM is a functionally
      active adhesion molecule, (b) its expression during the morphogenetic processes
      occurring during Xenopus laevis metamorphosis correlates with morphological
      changes in the cell-to-cell interaction; (c) Thyroxine is not directely involved
      in the activation of the expression of liver N-CAM.

PMID- 22358725
TI  - Foreword.

PMID- 22358724
TI  - A novel GPI-anchored glycoprotein shows properties of a coohterminus truncated
      cadherin involved in cell-cell contacts of cultured human epithelial cells.
AB  - We report the characterization of a cell-cell adhesion molecule identified by
      mAbBD31 on human epithelioid cells. This glycoprotein shows cadherin features but
      appears to be truncated being devoid of the transmembrane and cytoplasmic
      domains. It is directly membrane-anchored by a GPI moiety. We propose to call
      this molecule HT-cadherin.

PMID- 22358727
TI  - Editors comment.

PMID- 22358728
TI  - A European database for animal cell lines: Graz, Austria, 2 September 1989.

PMID- 22358726
TI  - Molecular characterization of adult-colonizing Streptococcus agalactiae from an
      area-based surveillance study in Romania.
AB  - One hundred and forty-eight colonizing isolates from adult Romanian women were
      conventionally serotyped and screened for antibiotic resistance. Capsular type
      assignment by multiplex polymerase chain reaction (PCR) was performed for
      nonserotypeable isolates. Tetracycline and macrolide resistance genes (tetM,
      tetO, tetL, ermA, ermB, and mefA) including tetM gene association with
      conjugative elements of the Tn916 family were searched. Molecular typing included
      PCR screening for major surface protein antigen genes (bac, bca, alp1, alp2/3,
      alp4, and rib), mobile genetic elements (GBSi1 and IS1548), and rapid detection
      of hypervirulent clone ST-17. Genetic diversity was assessed by pulsed field gel
      electrophoresis (PFGE) analysis of SmaI macrorestriction patterns. Among the
      colonizing isolates studied, serotypes V and III predominated and high rates of
      tetracycline and macrolide resistance were observed. The tetM gene occurred in
      140 tetracycline-resistant isolates and was associated with the int-Tn916 gene in
      94 of them. Most of the isolates displayed a constitutive MLS(B) phenotype (38/46
      isolates) and harbored the ermB gene. rib, alp2/3, and alp1 were the most common
      surface protein genes detected. Either IS1548 or GBSi1 intron were detected in
      almost half of the isolates and nine serotype III isolates belonged to clone ST
      17. PFGE analysis of SmaI macrorestriction patterns, obtained from 118 isolates,
      revealed an apparent genetic diversity.

PMID- 22358729
TI  - Bovine spongiform encephalopathy - a hazard to cell culture and biologically
      based medicines.

PMID- 22358730
TI  - Agitation and aeration effects in suspension mammalian cell cultures.
AB  - Three different hybridoma cell lines, grown in serum-free media with different
      levels of Pluronic F-68, were subjected to a shear force of 0.6 N m(-2). Some
      protective effect due to the polymer was found, indicating it to be a potentially
      useful adjuvant in serum-free media. Other observations of liquid and gas effects
      at the reactor level have been included here. A discussion of the difference
      between suspension and microcarrier cultures, in relation to hydrodynamic
      effects, is included.

PMID- 22358732
TI  - The use of a transport medium (L15M15) for bulk tissue storage and retention of
      viability.
AB  - Twenty-five human or mouse tissue samples, some up to 8*4*2 cm, were immersed in
      a special transport medium (TM), L15M15, up to 7 days before being processed or
      placed in tissue culture. To test the efficacy of this medium, we concurrently
      placed pieces of the same tissues in a sterile phosphate buffered solution (PBS).
      We also tested the preservative capabilities of TM and PBS at room temperature
      and with refrigeration. Differences between TM and PBS are demonstrated, which
      are more pronounced using room temperature up to 4 days time. The tissues stored
      in TM show fewer degenerative or autolytic changes than the same tissue stored in
      PBS under identical conditions. Using regrigeration further enhanced the
      preservative qualities of TM up to 4 days, but not PBS. There were no obvious
      differences between tissues stored in TM and PBS with refrigeration after 7 days.
      We conclude that transport medium L15M15 is a useful medium for preserving tissue
      viability, especially large tissue samples, up to 4 days, especially if
      refrigerated.

PMID- 22358731
TI  - An optimized culture medium for human vascular endothelial cells from umbilical
      cord veins.
AB  - Various polypeptide growth factors, culture substrates, basal media, sera and
      further supplements were assayed for improvement of growth of human vascular
      endothelial cells from umbilical cord veins. The resulting optimized medium
      consisted of gelatinized culture substrates, a mixture (1:1) of Iscove's MDM and
      Ham's F12 basal media supplemented with 20% newborn calf serum, 500 ng/ml crude
      fibroblast growth factor, 20 ng/ml epidermal growth factor, 5 MUg/ml transferrin,
      5 MUg/ml insulin and 10 MUg/ml heparin. The medium allowed long term cultivation
      of HUVEC up to 45 generations with maximal cell densities of about 10(5) cells
      per cm(2) and a minimal doubling time of about 14 hours at low cell densities.

PMID- 22358733
TI  - Discrimination of normal and transformed cells in vitro by cytologic and
      morphologic analysis.
AB  - Malignant A-549 lung carcinoma and adenovirus-12 SV40 hybrid virus transformed
      non-tumorigenic human bronchial epithelial cells (BEAS-2B) were objectively
      discriminated from normal bronchial epithelial (BE) cells on the basis of
      Papanicolaou stained nuclear features (e.g. shape, chromatin texture,
      hyperchromasia) and nucleolar morphology (e.g. number per cell, irregular
      contours). Morphometric analysis indicated that significant differences in
      cellular morphology existed between BE, BEAS-2B, and A-549 cells. Similar
      analyses of transformed, tumorigenic cell lines demonstrated that nuclear
      features (i.e., chromatin texture, clearing of parachromatin, hyperchromasia,
      variation in thickness of the nuclear envelope, sharp indentations in the nuclear
      envelope), and nucleolar features (i.e., degree of roundness, presence of angular
      projections, number per cell) discriminated chemically and virally transformed
      cells from spontaneously transformed cells. Nuclear and nucleolar features were
      correlated with the growth rate of tumorigenic cell lines. These analytical
      approaches will be helpful in studies of the effects of various factors (e.g.
      vitamin A, phorbol ester, oncogene transfection) on cellular proliferation and/or
      differentiation.

PMID- 22358734
TI  - Rhodamine 123 as a probe of in vitro toxicity in MDCK cells.
AB  - The effect of mercuric chloride on Madin-Darby Canine Kidney (MDCK) cells grown
      in culture was assayed by the mitochondrial-specific fluorescent probe, rhodamine
      123. Treatment of cells with mercuric chloride resulted in a dissipation of
      rhodamine fluorescence from the mitochondria into the cytoplasm, followed by a
      release into the medium bathing the cells. Toxicity was assayed either by
      determining the proportion of cells with delocalized rhodamine fluorescence, or
      by measuring the rhodamine released from or retained in the cells. Quantifying
      the release or retention of rhodamine 123 is semi-automated and represents a
      highly sensitive method of using a vital fluorescent dye for in vitro toxicity
      analysis.

PMID- 22358735
TI  - Image analysis of rat satellite cell proliferation in vitro.
AB  - Myogenic cells were isolated from adult rat skeletal muscles and cultured in
      vitro. Cell proliferation was analyzed between days 1 and 14. The cell cycle
      phases were determined by examining Feulgen-stained cultures with a cell image
      processor. The nuclei were automatically analyzed by calculating 18 parameters
      relating to the texture and densitometry of chromatin and the shape of each
      nucleus. Cell cycle phases were characterized (Moustafa and Brugal, 1984). The
      recognition methods made it possible to analyse the nuclei of the myogenic cell
      populations which were either involved in each phase of the mitotic cycle, or
      left out of the cycle after fusion into myotubes.After 3 hr of culture 10% of the
      cell population was involved in the cell cycle. In the presence of foetal calf
      serum, this percentage increased until day 3 after plating. At that time, the DNA
      content of 28.2% of the cell population was higher than 3C, whereas it is 2C in
      G1 or G0 nuclei; image analysis showed that 42% of these cells were in S or G2
      phase. From day 4, the proliferation rate gradually slowed down until day 8.
      After day 8, when numerous myotubes differentiated, the percentage of S and G2
      phase cells had diminished to between 3 and 8%. The percentage of nuclei in G0
      increased when the first myotubes differentiated around day 5. Myotube nuclei
      were largely in G0. When horse serum was added to the culture medium on day 4 to
      enhance myotube differentiation, significant cell proliferation was observed
      before cell fusion.These methods of analysis give the first daily pattern of
      myogenic cell proliferation and fusion in a cell population isolated from adult
      muscles.

PMID- 22358736
TI  - Effect of cell isolation methods and drug concentration on the use of the
      Differential Staining Cytotoxicity (DiSC) assay with solid tumours.
AB  - The Differential Staining Cytotoxicity (DiSC) in vitro drug sensitivity assay has
      been tested in solid tumours obtained from surgery. Various enzyme cocktails have
      been used for disaggregating cells for times ranging from 1-72 h. Collagenase
      (0.5%) plus DNase (0.002%) was chosen as producing the best results when
      incubated for 3 h at 37 degrees C. This cocktail was also used for 24, 48 and 72
      h incubations. Cell suspensions so produced were sometimes cleaned up by
      centrifugation on a Nycodenz gradient. Breast tumours were more often
      successfully cultured (67%) compared to gastrointestinal (43%) or other tumours
      (34%). Results with 6 drugs tested in 10 or more tumours suggested that in
      general, higher drug concentrations should be used when testing solid tumours as
      opposed to leukaemias in the DiSC assay.

PMID- 22358737
TI  - Effects of retinoic acid on the growth of cultured rabbit articular chondrocytes:
      Relation with alkaline phosphatase activity and beta receptor.
AB  - The effects of retinoic acid (RA) on rabbit articular cartilage cells were
      studied for concentrations ranging from 5.10(-5) M to 10(-7) M; the treatment
      with RA over three days resulted in dose dependent inhibition of chondrocyte
      proliferation between 5.10(-5) and 10(-5) M with persistence of the inhibitory
      effect until 10(-6) M. RA until 10(-7) M induced a slight, but significant,
      enhancement of cell proliferation. This growth stimulating effect seems to be
      related to the Beta receptor system because Beta blockers, such as sotalol and DL
      propranolol, were able to suppress the stimulating action of agonist type
      isoprenaline. The activity of alkaline phosphatase (AP) was also determined. The
      highest dose of RA (5.10(-5) M) induced an increase (x 3) of AP activity, and 10(
      7) M RA decreased it (x 0.4).

PMID- 22358738
TI  - First international symposium on marine molecular biology held at the Center of
      Marine Biotechnology, University of Maryland, Baltimore, Maryland on October 9
      11, 1988.

PMID- 22358739
TI  - Cultural aspects in the management of inborn errors of metabolism.
AB  - European Health Care Systems have not yet accommodated both previous and current
      migration waves. Children from immigrant families, especially children with
      chronic conditions, are particularly affected from the shortcomings in medical
      care. One condition, phenylketonuria (PKU), is an inborn error of metabolism
      (IEM) which results in intellectual disability unless treated with a lifelong
      phenylalanine (Phe) restricted diet. In our PKU clinic, patients from families
      who previously had emmigrated from the geographic area of Turkey to Austria,
      exhibited worse blood Phe control and cognitive development than comparable
      patients from native Austrian families. Using structured and semi-structured
      interviews, questionnaires, and illness narratives, we identified language,
      psychosocial, economic, educational and cultural barriers as factors influencing
      adherence to treatment. Our findings led us to conclude that access to
      interpreter services, exploration of the socio-cultural background and of family
      ecology, as well as bi-directional communication and medical decision making
      according to the "best interest of the child" principle, may improve outcomes in
      patients requiring complex treatment and care.

PMID- 22358741
TI  - Production of monoclonal antibodies and development of an ELISA for solamargine.
AB  - The ratio of hapten and bovine serum albumin in an antigen conjugate was
      determined by matrix-assisted laser desorption/ionization mass spectrometry. A
      hybridoma secreting monoclonal antibodies against solamargine was produced by
      fusing splenocytes immunized with a solamargine-bovine serum albumin conjugate
      with HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. Extensive cross
      reaction of anti-solamargine antibodies against solasonine appeared. Aglycone of
      solamargine, solasodine cross-reacted with anti-solamargine antibodies resulting
      in a 43.8% cross-reaction. Insignificant cross-reaction appeared with tomatine
      (2.06%). The full measuring range of the assay extends from 57.5 pmol ml(-1) to
      11.5 nmol ml(-1) of solamargine.

PMID- 22358740
TI  - Clinical overview and treatment options for non-skeletal manifestations of
      mucopolysaccharidosis type IVA.
AB  - Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem
      disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations,
      including short stature, skeletal dysplasia, cervical instability, and joint
      destruction, are known to be associated with this condition. Due to the severity
      of these skeletal manifestations, the non-skeletal manifestations are frequently
      overlooked despite their significant contribution to disease progression and
      impact on quality of life. This review provides detailed information regarding
      the non-skeletal manifestations and suggests long-term assessment guidelines. The
      visual, auditory, digestive, cardiovascular, and respiratory systems are
      addressed and overall quality of life as measured by endurance and other
      functional abilities is discussed. Impairments such as corneal clouding,
      astigmatism, glaucoma, hearing loss, hernias, hepatomegaly, dental abnormalities,
      cardiac valve thickening and regurgitation, obstructive sleep apnea,
      tracheomalacia, restrictive and obstructive respiratory compromise, and muscular
      weakness are discussed. Increased awareness of these non-skeletal features is
      needed to improve patient care.

PMID- 22358742
TI  - Metabolic burden in recombinant CHO cells: effect ofdhfr gene amplification
      andlacZ expression.
AB  - Foreign protein production levels in two recombinant Chinese hamster ovary (CHO)
      cell lines were compared in cells transfected with different expression vectors.
      One vector pNL1 contained the gene for neomycin resistance (neo ( r )) and
      thelacZ gene which codes for intracellular beta-galactosidase, with both genes
      controlled by the constitutive simian virus (SV40) promoter. The other vector
      CDbetaG contained the amplifiabledhfr gene andlacZ gene, controlled by the
      constitutive SV40 and cytomegalovirus (CMV) promoters, respectively. Cell growth
      and beta-galactosidase expression were compared quantitatively after cells were
      selected in different concentrations of the neomycin analog G418 and
      methotrexate, respectively. A 62% reduction in growth rate occurred in
      recombinant CHO cells in which thelacZ anddhfr genes were highly amplified and
      expressed. In contrast, the combined effects of the unamplifiedneo ( r ) gene
      andlacZ gene expression on the growth kinetics were small. Any metabolic burden
      caused bylacZ gene expression, which was evaluated separately from the effect
      ofneo ( r ) gene expression, must be negligible, as higher expression of beta
      galactosidase (1.5*10(-6) units/cell) occurred in unamplified cells compared to
      the cells in whichlacZ was amplified by thedhfr-containing vector (3*10(-7)
      units/cell). Thus, the main factor causing severe growth reduction ("metabolic
      burden") in cells containing the amplifieddhfr gene system was not overexpression
      of beta-galactosidase butdhfr andlacZ gene co-amplification anddhfr gene
      expression.

PMID- 22358743
TI  - Functional expression of human and mouse low density lipoprotein receptors in
      hybridomas.
AB  - Though a mouse.human-human heterohybridoma, N12-16.63, secreting an antitetanus
      toxoid human monoclonal antibody grew well in a serum-free medium, its high
      producing subclone N12-69 required SSGF-I, a low density lipoprotein (LDL) from
      swine serum, or human-LDL (h-LDL) for growth. The growth-promoting action of SSGF
      I was caused by its lipid fraction, and SSGF-I could be replaced completely with
      cholesterol in the presence of bovine serum albumin (BSA). Thus, cell line N12-69
      is a cholesterol auxotroph of the heterohybridoma. N12-69 cells express both
      mouse and human LDL receptors on the cell surface in a ratio of 1:4. SSGF-I bound
      to both receptors with the same binding affinity, and h-LDL was also take up by
      the same receptors, though the affinity constant of the receptors for SSGF-I was
      1.5 times stronger than that for h-LDL. The growth of N12-69 cells was completely
      inhibited by the addition of dextran sulfate, which is known to inhibit the
      binding of LDL to LDL receptors, to an SSGF-I or h-LDL containing medium but was
      not inhibited at all when dextran sulfate was added to a serum-free medium
      supplemented with cholesterol and BSA. Furthermore, an anti-human LDL receptor
      monoclonal antibody partially inhibited the growth of N12-69 cells in an SSGF-I
      or h-LDL containing medium. These findings suggest that N12-69 cells express both
      biologically active mouse and human LDL receptors on their cell surfaces and that
      SSGF-I or h-LDL is taken up by the both receptors to be utilized as a cholesterol
      source for the growth.

PMID- 22358744
TI  - Large scale transient expression with COS cells.
AB  - We demonstrate here that transient expression with COS cells can be performed at
      the one litre scale for a period of more than 10 days. Cells grown in T225 flasks
      were transfected by electroporation, transferred into spinners, and then grown
      either in suspension or on microcarriers. A daily medium change significantly
      extented culture life and production time, compared with standard
      protocols.Concentrations of the product, the secreted fusion protein CD40-Fc,
      were comparable in microcarrier and suspension culture. Cultures were started in
      fetal calf serum containing medium and the subsequent production process was
      performed in a low protein serum free medium which allowed easy downstream
      processing. 10 litres of supernatant, collected from one transfected batch of
      cells, yielded 30 mg of purified and biologically active protein.In addition to
      developing a simplified protocol for generation of cells we also reduced the
      material (DNA, cuvettes) required for electroporation. Our results show that
      scale up of transient expression to the litre scale can be successfully acieved.
      This provides a new tool to generate milligram quantities of protein within weeks
      of gene cloning.

PMID- 22358745
TI  - Microcarrier cultivation of bovine aortic endothelial cells in spinner vessels
      and a membrane stirred bioreactor.
AB  - Primary bovine aortic endothelial cells were cultivated in serum supplemented
      medium without any additional growth factors. The anchorage dependent cells were
      propagated on Dormacell((r)) microcarriers with covalently bound dimeric DEAE
      groups at the surface of the dextrane beads. Cultivations were performed in 200
      ml spinner cultures containing 1 g l(-1) to 3 g l(-1) of microcarriers. Out of
      five types of Dormacell((r)) microcarriers with different ion exchange capacities
      ranging from 0.30 up to 0.65 meq g(-1), corresponding to nitrogen contents from
      1.2% to 2.9%, respectively, optimal attachment and growth of endothelial cells
      were obtained with beads of highest nitrogen content (2.9%). Cells were seeded
      withca. 5 viable cells per microcarrier being sufficient to achieve fully
      confluent microcarriers after 4 to 5 days. Glucose concentrations decreased from
      21 mM to uppermost half of the original concentrations. 4 mM glutamine was
      rapidly consumed and virtually exhausted after the cells reached confluency.
      Lactate concentrations raised to a maximum of 7 mM in spinner cultures, but was
      found to be reutilized in the stationary phase after glutamine limitation
      occurred. Serine was found to be the second most prominent amino acid being
      almost exhausted at confluency whereas alanine was produced in noteworthy
      amounts. Considerable decrease was determined for threonine, lysine and arginine;
      low consumption rates were observed for leucine, phenylalanine and methionine.
      All other amino acids did not alter significantly throughout cultivation. These
      data support that bovine aortic endothelial cells are capable to utilize glucose
      and glutamine as well as lactic acid (after glutamine exhaustion) as energy
      and/or carbon source. Finally, batch cultures in a 2 liter membrane stirred
      bioreactor with bubble-free aeration were performed to produce large quantities
      of endothelial cells using microcarrier concentrations of 3 g l(-1).

PMID- 22358746
TI  - The use of serum-free medium for the production of functionally active humanised
      monoclonal antibody from NS0 mouse myeloma cells engineered using glutamine
      synthetase as a selectable marker.
AB  - A protein-free growth medium (W38 medium) had previously been developed for the
      NS0 mouse myeloma cell line which is cholesterol-auxotrophic. This paper
      describes the development of a protein-free growth medium for NS0 cells
      expressing humanised monoclonal antibody using GS (glutamine synthetase) as a
      selectable marker. Several GS-engineered NS0 cell lines expressing humanised
      monoclonal antibody grew in a modification of W38 medium which maintained GS
      selection, supplemented with cholesterol, phosphatidylcholine and beta
      cyclodextrin. Further studies showed that additional glutamic acid, asparagine,
      ribonucleosides and choline chloride improved cell growth. Amino acid analysis
      identified a number of amino acids that were being depleted from the culture
      medium. NS0 cell lines 9D4 and 2H5 expressing CAMPATH-1H(*) were adapted to
      enable them to grow serum-free in the absence of cholesterol and beta
      cyclodextrin. Cholesterol-independent 9D4 (9D4.CF) cells grown in shake flask
      culture using an enriched protein-free medium (WNSD medium), supplemented with
      human recombinant insulin (Nucellin), reached a maximum cell density to
      1.86*10(6) cells ml(-1) producing 76.6 mg l(-1) of antibody. CAMPATH-1H antibody
      produced using serum-free medium was found to be functionally activein vitro in
      the Antibody Dependant Cellular Cytotoxicity (ADCC) assay.

PMID- 22358747
TI  - Use of XTT for quantitating clonogenic growth in soft agar.
AB  - The purpose of this study was to investigate the use of the tetrazolium salt.
      XTT, in a microassay for quantitation of anchorage-independent growth of cells in
      soft agar, using two human ovarian tumour cell lines (OAW 42 and OAW 28). The
      response of OAW 42 to Cis-platinum, EGF, TGF beta and insulin, and of OAW 28 to
      EGF, TGF beta and insulin were determined both by visual colony counting and use
      of the XTT assay. Drug inhibition and growth factor inhibition and stimulation
      were clearly demonstrated, with increases or decreases in visually counted colony
      numbers being paralleled by increases or decreases in optical density values
      obtained by using XTT. The XTT colorimetric assay was simple to perform and
      reproducible with low variability, and was found to be an acceptable alternative
      to visual colony counting for the quantitation of cell line response to drugs and
      growth factors under anchorage-independent growth conditions.

PMID- 22358748
TI  - Anin vitro model for chick embryonic notochords.
AB  - A two step method to obtain mesenchymal free 3.5 day old chick embryonic
      notochordsin vitro is presented. 1.) Notochords are isolated by mechanical
      microdissection from the embryos below the head and above the leg-buds. 2.) The
      dissected notochords are trypsinized to eliminate contaminating mesenchymal
      cells, while the perinotochordal sheath (PNS) is retained. After isolation and
      trypsinization, notochords are cut in standard 8mm lengths, explantedin vitro and
      incubated at 37 degrees C. Immediately before incubation and after 3 and 6 daysin
      vitro, notochords are fixed and stained to follow the morphological changes. The
      total DNA content of notochords is measured before and during maintenancein vitro
      to evaluate their metabolic activities. Results show that during thein vitro
      period, the isolated mesenchymal free notochordal fragments can conserve their
      characteristic architecture. The total DNA content measurements indicate
      proliferative activity and a high viability of the notochords in ourin vitro
      system. In the present study, an isolation andin vitro method is offered which
      might be an effective tool to study the metabolic activities of chick embryonic
      notochordsin vitro in comparison toin vivo behaviour, in order to study the
      underlying mechanism of notochord regression.

PMID- 22358749
TI  - Erratum Assessment of heterologous membrane protein polarity in transiently
      transfected MDCK cells.

PMID- 22358750
TI  - Development of human monoclonal antibodies: A review.
AB  - This article describes the current status in the development of human monoclonal
      antibodies. Over the last ten years a lot of information about the human immune
      system has emerged. Combining these with the many new (bio-)technologies it is
      plausible that the long awaited breakthrough of this technology is close. This
      paper focuses on the "classical" cell-biological methods of achieving stable,
      antibody-producing human cell lines via cell fusion methods or virus derived
      transformations of human B-lymphocytes, as well as genetic engineering methods
      e.g. DNA libraries or phage display technology. The available in vitro
      immunization methods are critically reviewed and their impact on this topic is
      discussed. Therapeutic applications for cancer treatment or passive immunization
      against infectious diseases with antibodies derived by both ways are also
      reviewed.

PMID- 22358751
TI  - Culture of cells from tissues of adult and larval sea lamprey.
AB  - Methods were developed for the culture of cells derived from tissues of the sea
      lamprey (Petromyzon marinus). Cultures were initiated from gill, liver, muscle
      and gut from larvae and newly transformed individuals and brain, heart, kidney
      and ovary from sexually mature adults. The lamprey cells were viable for up to
      six months in culture and cells from ovary, muscle, gut, gill and liver were
      propagated for multiple passages. For all cultures except liver, optimal cell
      attachment and spreading was obtained on surfaces coated with fibronectin and
      collagen. Optimal liver cell attachment was achieved on basement membrane. Cells
      synthesizing DNA were detected by precursor incorporation in five week-old
      cultures derived from adult and larval tissues. Metabolic labeling experiments
      with [(35)S]-methionine demonstrated that cultures initiated from liver and ovary
      continued to synthesize and release proteins into the medium for several weeks.
      Ultrastructural examination revealed the presence of ciliated cells in cultures
      from brain and the accumulation of lipid in epithelial cells derived from liver
      and gill.

PMID- 22358752
TI  - Production of recombinant h-AT III with mammalian cell cultures using capillary
      electrophoresis for product monitoring.
AB  - The importance of mammalian cell cultures for biotechnological production
      processes is steadily increasing, despite the high demands of these organisms on
      their culture conditions. Efforts towards a more efficient bioprocess generally
      concentrate on maximizing the culture's life time, the cell number, and the
      product concentration. Here recombinant BHK 21 c13 cells are used to produce rh
      AT III, an anticoagulant of high therapeutic value. The influence of the process
      mode (batch, repeated batch, continuous perfusion) and the process temperature
      (30 degrees C vs. 37 degrees C) on the above mentioned parameters is
      investigated. It is possible to increase the length of the culture from 140 h
      (batch) to more than 500 h (continuous perfusion culture), while concomitantly
      increasing the cell density from 0.72 10(6)/ml (batch) to 2.27 10(6)/ml (repeated
      batch) and 2.87 10(6)/ml (continuous perfusion culture). The accumulation of
      toxic metabolites, such as lactate, can be curtailed by reducing the bioreactor
      temperature from 37 degrees C to 30 degrees C during the later part of the
      exponential growth phase. Fast and reliable product monitoring became essential
      during process optimization. Capillary zone electrophoresis (CZE) in uncoated
      fused silica capillaries was studied for that purpose and compared to the
      standard ELISA. Under optimized conditions an AT III quantification could be done
      within 2 min with CZE. The detection limit was 5 MUg/ml. A relative standard
      deviation of less than 0.9% was calculated. The detection limit could be lowered
      by one order of magnitude by using a two dimensional system, where an liquid
      chromatographic (LC) system is coupled to the CZE. Concomitantly the resolution
      is improved. The two-dimensional analysis required 5 min. Membrane adsorbers (MA)
      were used as stationary phase in the LC-system, to allow the application of high
      flow rates (5-10 ml/min). The correlation between the LC-CZE analysis and the
      standard AT III-ELISA was excellent, with r(2): 0.965. Using the assay for at
      line product monitoring, it is shown, that the process temperature is of no
      consequence for the productivity whereas the process mode strongly influences
      this parameter.

PMID- 22358753
TI  - Strategies for maximizing metallothionein promoter regulated recombinant protein
      production in mammalian cell cultures.
AB  - A stably transformed BHK cell line, engineered to produce a human transferrin
      half-molecule under the control of a mouse metallothionein (MT) promoter, was
      used as a model system to develop strategies to increase inducible recombinant
      protein production. Gene expression regulated by the MT promoter is induced by
      heavy metals (e.g. Zn(+2) or Cd(+2)) in a dose dependent fashion. However, at
      high concentrations these metals are toxic to cells. Culture protocols which
      balance these counteractive effects are needed to maximize transferrin
      production. Fully induced cells produced up to 0.7 pg transferrin/cell.h, a 3
      fold increase in production over uninduced levels. Cell growth was inhibited at
      Cd(+2) dosages above 1 fmol/cell; prolinged exposure at this dosage was
      cytotoxic. Cell specific transferrin productivities decreased within 48 h
      following induction with Cd(+2) although cell-associated Cd(+2) levels remain
      high. Further addition of Cd(+2) to cultures restored cell specific transferrin
      production rates. This suggests that cell associated Cd(+2) is sequestered into a
      form which does not stimulate the MT promoter. Cd(+2) dosing regimes which
      maintained cell associated Cd(+2) concentrations between 0.2 and 0.35 fmol/cell
      ensured cell growth and high cell specific productivities which maximized final
      product titers. For routine batch culture, initial Cd(+2) loadings of 0.8
      fmol/cell gave near-maximum transferrin production levels. For extended culture,
      repeated small doses of 0.5 fmol/cell every 24 to 48 h maximized transferrin
      synthesis with this cell line.

PMID- 22358754
TI  - Improved protocols for the isolation and in-situ cryopreservation of cell
      colonies.
AB  - Stable transfection and cloning of cells often require physical separation of
      cell colonies. In order to conveniently isolate cell clones from petri dishes, we
      developed a protocol starting with a soft agar overlay of cells. This reduces the
      risk of cell diffusion between different colonies. Cells from individual colonies
      are mechanically removed, incubated with trypsin, and cell suspensions are seeded
      onto parallel microtiter plates. The cell clones on one microtiter plate can be
      cryopreserved in situ using the protocol described here which was tested for a
      variety of cell lines. Replica plates can be used for screening and further
      expansion of interesting clones. If screening can also be performed in situ,
      e.g., by immunocytochemistry, immunofluorescence, or the polymerase chain
      reaction, it is possible to perform most steps necessary in cell cloning
      experiments on microtiter plates.

PMID- 22358755
TI  - Rapid authentication of animal cell lines using pyrolysis mass spectrometry and
      auto-associative artificial neural networks.
AB  - Pyrolysis mass spectrometry (PyMS) was used to produce biochemical fingerprints
      from replicate frozen cell cultures of mouse macrophage hybridoma 2C11-12, human
      leukaemia K562, baby hamster kidney BHK 21/C13, and mouse tumour BW-O, and a
      fresh culture of Chinese hamster ovary CHO cells. The dimensionality of these
      data was reduced by the unsupervised feature extraction pattern recognition
      technique of auto-associative neural networks. The clusters observed were
      compared with the groups obtained from the more conventional statistical
      approaches of hierarchical cluster analysis. It was observed that frozen and
      fresh cell line cultures gave very different pyrolysis mass spectra. When only
      the frozen animal cells were analysed by PyMS, auto-associative artificial neural
      networks (ANNs) were employed to discriminate between them successfully.
      Furthermore, very similar classifications were observed when the same spectral
      data were analysed using hierarchical cluster analysis. We demonstrate that this
      approach can detect the contamination of cell lines with low numbers of bacteria
      and fungi; this approach could plausibly be extended for the rapid detection of
      mycoplasma infection in animal cell lines. The major advantages that PyMS offers
      over more conventional methods used to type cell lines and to screen for
      microbial infection, such as DNA fingerprinting, are its speed, sensitivity and
      the ability to analyse hundreds of samples per day. We conclude that the
      combination of PyMS and ANNs can provide a rapid and accurate discriminatory
      technique for the authentication of animal cell line cultures.

PMID- 22358756
TI  - Quantitative comparison of rat hepatocyte functions in two improved culture
      systems with or without rat liver epithelial cell line.
AB  - We quantitatively evaluated two recently-developed novel techniques for
      hepatocyte cultivation in a dish level; that is, spheroid culture and membrane
      supported collagen (CN) gel sandwich culture, in terms of cellular maintenance,
      albumin secretion and 7-ethoxycoumarin (7EC) metabolism to 7-hydroxycoumarin
      (7HC) as a marker for cytochrome P450 IA1 activity in the presence and absence of
      rat liver epithelial cell line (RLEC) during one month of culture, together with
      conventional coculture with RLEC in CN-coated dishes as a control. RLEC prevented
      spheroid loss caused by its detachment from the culture dishes often occurring in
      pure culture. CN-gel sandwich by itself improved remarkably hepatocyte
      maintenance when compared with CN-gel free systems, thereby resulting in
      enhancement of overall functional expressions as compared with CN-gel free
      systems. RLEC in CN-gel sandwhich, however, reduced cellular sustainment probably
      due to its suppression of hepatocyte growth. Although there were no significant
      differences in albumin secretion per cell among the five cultures examined, CN
      gel sandwich expressed markedly higher 7EC metabolizing activity per cell, where
      RLEC presence had a preferable influence. Consequently, membrane-supported CN-gel
      sandwich was the most superior technique for hepatocyte cultivation from the
      standpont of both cellular maintenance and its functional expressions per cell.

PMID- 22358757
TI  - Mammalian artificial chromosomes: A review.
AB  - A mammalian artificial chromosome (MAC) may be assembled through the
      juxtapposition of three kinds of DNA elements: a centromere, several DNA
      replication origins, and two telomeric repeats. The resulting structure should be
      able to carry and express one or more selected genes (transgenes), introduced for
      specific purposes. The minimal length is unknown, but may be of several Mb.Of its
      basic elements, the telomeres may present lesser problems, in view of their
      simple composition and organization. Centromeres could be an issue, given their
      many unknowns. Mammalian DNA replication origins are at present poorly
      characterized, but it is expected that at least one may be contained within the
      MAC components, especially the transgene. Their overall assembly may require a
      combination of in vivo and in vitro approaches.A promising strategy aims at
      constructing two telomeric arms of a MAC, one of which may include the transgene.
      The two novel arms could acquire a functional centromere through recombination
      with the two arms of a resident chromosome. Alternatively, if the two telomeric
      constructs are also endowed with properly placed and oriented centromeric
      sequences, a centromere may be rescued in vivo by homologous recombination with
      the external parts of the centromere of the resident chromosome. Positive
      selection for the artificial arms and counterselection against the resident arms
      should facilitate the assembly process.The assembly of such construct would not
      change the ploidy number of the host cell. After loading of a transgene, however,
      the resulting MAC may be isolated and transferred into an expression cell, where
      it may represent a novel chromosomal element. In this case untoward effects to
      the host cell may derive from an ensuing dosage effect for the transgene(s)
      rather than from the presence of a MAC per se.A MAC may contribute to a deeper
      understanding of the structural requirements for chromosomal function and
      evolution as well as the mechanism of chromatin formation. It should also help in
      the development of second generation vectors for transfer of Mb-long DNA
      sequences, as required for properly regulated mammalian gene function as well as,
      possibly, for therapy.

PMID- 22358758
TI  - Hybridomas in a bioreactor cascade: modeling and determination of growth and
      death kinetics.
AB  - Hybridomas were cultured under steady-state conditions in a series of two
      continuous stirred-tank reactors (CSTRs), using a serum-free medium. The
      substrate not completely converted in the first CSTR, was transported with the
      cells to the second one and very low growth rates, high death rates, and lysis of
      viable cells were observed in this second CSTR. These conditions are hardly
      accessible in a single vessel, because such experiments would be extremely time
      consuming and unstable due to a low viability. In contrast to what is often
      observed in literature, kinetic parameters could thus be derived without the
      neccessity for extrapolation to lower growth rates. Good agreement with
      literature averages for other hybridomas was found. Furthermore, showing that the
      reactor series is a valuable research tool for kinetic studies under extreme
      conditions, the possibility to observe cell death under stable and defined steady
      state conditions offers interesting opportunities to investigate apoptosis and
      necrosis. Additionally, a model was developed that describes hybridoma growth and
      monoclonal antibody production in the bioreactor cascade on the basis of
      glutamine metabolism. Good agreement between the model and the experiments was
      found.

PMID- 22358759
TI  - Suppressive effect of spinach extract on the formation of melanin in B16 mouse
      melanoma cells.
AB  - A non-dialyzable extract of fresh spinach leaves exhibited a strong antioxidant
      activity towards oxidation of linoleic acid and suppressed the melanin formation
      of a mouse melanoma cell line, B16 melanoma 4A5, without any significant effect
      on the proliferation of cells.

PMID- 22358760
TI  - Can macroscopic identification of large ovarian follicles be useful in
      eliminating follicles with impaired steroid function?
AB  - "In vitro" studies, commonly using porcine ovarian follicles, may generate
      inconsistent results when atretic follicles are not eliminated from the pool of
      experimental follicles. The present experiment was conducted to test the
      practical value of the macroscopie identification of large porcine follicles,
      which were assumed to be atretic. Histological observations of hematoxylin-eosin
      stained follicular sections confirmed the results of the macroscopic
      classification. The follicles classified as presumably abnormal revealed signs of
      atresia at the light microscopic level. Such follicles (type 2) showed decreased
      levels of estradiol and androgens in comparison with the healthy-looking
      follicles (type 1).Steroid analysis also revaled that practically all estradiol
      from an ovarian follicle could be detected in the follicular fluid, whereas
      androgens extracted from follicular fluid represented approximately half of the
      total amount of follicular androgens.The experimental results indicate that the
      introduced macroscopic classification could be helpful in eliminating follicles
      with an impaired steroid function.

PMID- 22358761
TI  - Increased production of recombinant hIGFBP-1 in PEG induced autofusion of Chinese
      hamster ovary (CHO) cells.
AB  - A recombinant Chinese hamster ovary (CHO) cell clone, S1, stably expressing human
      insulin-like growth factor binding protein-1 (hIGFBP-1), was treated with
      polyethylene glycol (PEG), resulting in cell fusion, in order to further enhance
      the protein expression by increasing the gene copy number and/or the amount of
      organelles important to the protein expression/-secretion. Both the fused cell
      line, Peg1, and its mother cell line, S1, were adapted to serum-free growth in
      suspension and were characterised with respect to growth and productivity. Peg1
      was easier to adapt to the serum-free suspension conditions and had a higher
      viability during the adaptation period than S1. Furthermore, Peg1 showed a stable
      productivity of hIGFBP-1 that was twice as high as that for S1 under both
      adherent and suspension conditions. A considerable difference in the specific
      productivity (up to 3-4 times) was noticed during the growth phase. PEG fusion
      experiments have earlier been studied in our laboratory with CHO cells producing
      recombinant factor VIII and our results correlates very well with the results
      obtained with the factor VIII producing cells. Surprisingly, it was possible to
      obtain high producing recombinant cell lines, which were stable for more than 4
      months.

PMID- 22358762
TI  - Stable, recombinant expression of human insulin-like growth factor binding
      protein-1 (hIGFBP-1) in Chinese hamster ovary (CHO) cells.
AB  - Stable expression of human insulin-like growth factor of binding protein-1
      (hIGFBP-1)at high levels has been achieved in Chinese hamster ovary (CHO) cells
      by co-transfection and subsequent co-amplification of expression vectors
      containing the hIGFBP-1 cDNA and a dihydrofolate reductase (DHFR) cDNA gene into
      DHFR-deficient cells. Stepwise selection of the DHFR(+) transformants in
      increasing concentrations of methotrexate (MTX) generated cells which had high
      copy numbers of the hIGFBP-1 gene (around 100 copies in cells amplified in medium
      containing 100 nM MTX). Expression of hIGFBP-1 in mixed clones was found to
      increase with increasing copy number and an apparent correlation between intra-
      and extracellular levels of hIGFBP-1 produced by these cells was observed. It was
      further observed that continuous cultivation over eight months in medium
      supplemented with 100 nM MTX increased the production of hIGFBP-1 25 times. The
      productivity did not increase further after five more months cultivation in MTX
      containing medium. A subcloning of this cell line gave clones with an even higher
      productivity. Further amplification in 500 nM or 1 uM MTX did not increase the
      hIGFBP-1 production.

PMID- 22358764
TI  - Deletion of the kappa genes from mouse hybridomas established with NS-1 myelomas.
AB  - Monoclonal antibodies (mAbs) of the IgG class produced by mouse hybridomas raised
      with NS-1 myelomas have been shown to contain two types of immunoglobulin light
      (kappa) chains derived from the myelomas and antigen-stimulated spleen
      lymphocytes, and the hybridomas produce three mAb species with light chain
      heterogeneity (Abe and Inouye, 1993). In the present study, 9 hybridoma lines
      secreting homogeneous mAbs have been isolated from 63 lines cloned from an
      established hybridoma line producing three mAbs. They secrete homogeneous mAbs
      containing light chains derived from either myeloma or spleen cells. They contain
      either kappa gene derived from the respective cells, and the other gene was
      deleted during the cultivation. The deletion frequency of the kappa gene of
      myelomas is 3 times higher than that of spleen cells, although 80-85% of
      hybridomas reach the stable state containing both kappa genes.

PMID- 22358763
TI  - Development of resting membrane potentials in differentiating murine
      neuroblastoma cells (N1E-115) evaluated by flow cytometry.
AB  - With the aid of a voltage-sensitive oxonol dye, flow cytometry was used to
      measure relative changes in resting membrane potential (V(m)) and forward angle
      light scatter (FALS) profiles of a differentiating/differentiated murine
      neuroblastoma cell line (N1E-115). Electrophysiological differentiation was
      characterized by V(m) establishment. The (V(m))-time profile was found to be seed
      cell concentration-dependent for cell densities of less than 2 * 10(4)
      cells/cm(2). At higher initial cell densities, under differentiating culture
      conditions, V(m) development commenced on day 2 and reached a steady-state on day
      12. The relative distribution of differentiated cells between low and high FALS
      has been proposed as a potential culture electrophysiological differentiation
      state index. These experiments offer a general methodology to characterize
      cultured excitable cells of nervous system origin, with respect to
      electrophysiological differentiation. This information is valuable in studies
      employing neuroblastoma cells as in vitro screening models for safety/hazard
      evaluation and/or risk assessment of therapeutical and industrial chemicals under
      development.

PMID- 22358765
TI  - Flow cytometric analysis of sialyl Lewis A antigen on human cancer cells by using
      F(ab')2MU fragments prepared from a mouse IgM monoclonal antibody.
AB  - F(ab')2 fragments, herein designated as F(ab')2MU fragments, were prepared from a
      mouse IgM monoclonal antibody specific to sialyl Lewis A antigen. The fragments
      were applied to flow cytometry to analyze the antigen on human cancer cells. The
      binding of the fragments to the antigen-positive cells was stronger than that of
      the original IgM. The non-specific binding of the IgM antibody to the antigen
      negative cells was much decreased by using the F(ab')2MU fragments. These results
      indicate that the F(ab')2MU fragments are more suitable than the original IgM
      monoclonal antibody in flow cytometric analysis.

PMID- 22358766
TI  - Proteolytic cleavage of recombinant two-chain factor VIII during cell culture
      production is mediated by protease(s) from lysed cells. The use of pulse
      labelling directly in production medium.
AB  - During the production by mammalian cells of recombinant factor VIII from which
      the B domain was deleted (rFVIII), proteolytic cleavages in the C-terminal part
      of the heavy chain were observed (Kjalke et al., 1995). By radioactive pulse
      labelling it was investigated whether the cleavages took place inside the cells
      during protein synthesis or after release in the medium. The rFVIII-producing CHO
      (Chinese hamster ovary) cells were cultured in the presence of (35)S-methionine
      and then the cell lysate and the conditioned media were immunoprecipitated and
      analyzed by electrophoresis. By pulse labelling and chasing for various time
      periods, it was shown that the cleavages only took place after secretion of the
      protein from the cells. Adding cell lysate to uncleaved rFVIII caused cleavage of
      the heavy chain, as seen by loss of binding to a monoclonal antibody specific for
      intact rFVIII, indicating that the cleavage was performed by proteinase(s)
      released from the lysed cells. By incubating intact rFVIII with the
      multicatalytic proteinase (proteasome) present in cytoplasm and nucleus of
      eukaryotic cells, loss of binding to the monoclonal antibody was observed. This
      indicates that the multicatalytic proteinase, released from lysed rFVIII
      producing cells, could be responsible for the cleavage of rFVIII. Among several
      protease inhibitors tested, only bacitracin was found to diminish the extent of
      cleavage. Phosphatidylserine also protected rFVIII against cleavage, probably by
      binding to rFVIII.

PMID- 22358767
TI  - Prolonged lidocaine metabolizing activity of primary hepatocytes with spheroid
      culture using polyurethane foam as a culture substratum.
AB  - Primary rat hepatocytes formed spheroids in the pores of polyurethane foam (PUF)
      used as a culture substratum. The hepatocytes in monolayer and spheroid
      stationary culture converted lidocaine to monoethylglycinexylidide (MEGX) which
      was N-deethylation of lidocaine. The metabolic activity of the
      hepatocytes/spheroid stationary culture system was 1.5~2.0-fold higher than that
      of monolayer culture for 10 days. The activity of albumin production and cell
      survival of hepatocytes in monolayer and spheroid cultures decrease due to
      lidocaine treatment dependend on the lidocaine concentration, but the activity
      and cell survival in PUF/spheroid stationary culture were maintained at a higher
      level than that in monolayer culture under the lidocaine treatment. We developed
      a device for an in vitro liver model, drug metabolism simulator (DMS), using a
      PUF/spheroid packed-bed module including 4.00 +/- 0.68 * 10(7) hepatocytes and
      analyzed pharmacokinetics of lidocaine in a one-compartment model. Lidocaine
      clearance and extraction ratio of hepatocytes in the DMS corresponded to 1.354 +/
      0.318 ml/min/g-liver and 0.677 +/- 0.0159/g-liver, respectively (N=4). These
      values were comparable with in vivo values, 1.930 ml/min g-liver and 0.965/g
      liver reported by Nyberg (1977). Consequently, PUF/spheroid culture maintained
      high lidocaine metabolizing activity over a long term and seems to provide a
      promising culture system as a drug metabolism simulator which will be used for
      drug screening, cytotoxicity tests and prediction of pharmacokinetics.

PMID- 22358768
TI  - Recombinant Human Albumin in Cell Culture: Evaluation of Growth-Promoting
      Potential for NRK and SCC-9 Cells In Vitro.
AB  - Serum-derived albumin has for a long time been used in cell culture media, but
      the exact role of albumin and/or impurities bound to albumin has not been
      precisely defined. In this study, recombinant human albumin was evaluated for its
      growth-promoting activity on two cell lines, NRK and SCC-9. For NRK cells, the
      recombinant human albumin was found to exert an inhibitory effect. The fact that
      fatty acid free HSA was also inhibitory while HSA fraction V was stimulatory
      suggested a role for fatty acids or some other bound moieties in growth
      stimulation by HSA fraction V. Addition of oleic acid, cholesterol,
      phosphatidylcholine, phosphatidylserine or a combination of these lipids,
      however, did not significantly improve the growth stimulating activity of either
      fatty acid free HSA or the recombinant human albumin. For SCC-9 cells, both
      recombinant human albumin and fatty acid free HSA showed slight stimulation
      (although they were not as active as HSA fraction V), suggesting that in some
      cell systems, the albumin molecule per se may promote cell growth and survival.

PMID- 22358769
TI  - Gene delivery into neuronal and glial cells by using a replication-deficient
      adenovirus vector: prospects for neurological gene therapy.
AB  - We have used a recombinant adenovirus vector (E1-) expressing beta-galactosidase
      to explore a novel mechanism with which to transfer genes into cells of the
      central nervous system (CNS). The replication-deficient adenovirus vector
      expressing beta-galactosidase (RAd35) was propagated on a permissive helper cell
      line (293 cells). High level protein expression from the human cytomegalovirus
      immediate early promoter (hCMV IE) was obtained in a target cell population of
      RAd35 infected cultured neuronal and glial cell lines. Light microscopy showed
      that over 50% of the glial cells studied expressed beta-galactosidase. Following
      retinoic acid treatment, RAd35 infected cell lines ND7/23, NG108 and NTera2,
      showed beta-galactosidase expression in up to 90% of the cells. In addition,
      these cells showed morphological evidence of differentiation into neurons. This
      pattern of beta-galactosidase expression was also observed in primary rat
      cerebella granule neuron cultures. In vivo studies were performed in Balb/c mice
      following direct intracranial injections of RAd35 into the brain. Cell sections
      showed a localised staining in the brain at the site of injection of the virus.
      Non-replicating adenovirus vectors are therefore highly efficient systems for
      delivering a transgene into brain cells. However, their broad cell tropism may
      limit their applications for genetic disorders in which a specific cell type is
      to be targeted for gene therapy. To address this problem, we have constructed
      adenovirus vectors which contain specific neuronal promoters and are currently
      assessing in vitro expression.

PMID- 22358770
TI  - Erratum; Assessment of virus infection in cultured cells using metabolic
      monitoring.

PMID- 22358771
TI  - Erratum: Degradative activities in a recombinant chinese hamster ovary cell
      culture.

PMID- 22358772
TI  - Phototoxic effect of curcumin on methicillin-resistant Staphylococcus aureus and
      L929 fibroblasts.
AB  - Photodynamic therapy has been investigated as an alternative method of killing
      pathogens in response to the multiantibiotic resistance problem. This study
      evaluated the photodynamic effect of curcumin on methicillin-resistant
      Staphylococcus aureus (MRSA) compared to susceptible S. aureus (MSSA) and L929
      fibroblasts. Suspensions of MSSA and MRSA were treated with different
      concentrations of curcumin and exposed to light-emitting diode (LED). Serial
      dilutions were obtained from each sample, and colony counts were quantified. For
      fibroblasts, the cell viability subsequent to the curcumin-mediated photodynamic
      therapy was evaluated using the MTT assay and morphological changes were assessed
      by SEM analysis. Curcumin concentrations ranging from 5.0 to 20.0 MUM in
      combination with any tested LED fluences resulted in photokilling of MSSA.
      However, only the 20.0 MUM concentration in combination with highest fluence
      resulted in photokilling of MRSA. This combination also promoted an 80% reduction
      in fibroblast cell metabolism and morphological changes were present, indicating
      that cell membrane was the main target of this phototherapy. The combination of
      curcumin with LED light caused photokilling of both S. aureus strains and may
      represent an alternative treatment for eradicating MRSA, responsible for
      significantly higher morbidity and mortality and increased healthcare costs in
      institutions and hospitals.

PMID- 22358773
TI  - Effects of platelet derived growth factor (PDGF) on fibronectin (FN) production
      by human skin and scar fibroblasts.
AB  - The fibroblast-type cell found in hypertrophic scars and keloids demonstrates an
      elevated fibronectin (FN) production, compared to the same type of cell in normal
      dermis. We wished to determine if the effects of platelet derived growth factor
      (PDGF) on FN production in these cell types would be equivalent or different.
      Cell lines were established from the dermis (reticularis) of hypertrophic scars,
      keloids, uninvolved normal skin adjacent to the lesions, including an assumed
      normal skin adjacent to a keloid (AS), and normal skin from a different uninjured
      patient (DS). Each parent tissue from which the cell lines originated was
      diagnosed histologically. Each hypertrophic scar, keloid and normal adjacent
      skin, with one exception, showed typical histologic findings confirming the
      clinical diagnosis. DS was also normal. AS, although assumed to be normal, in
      fact, demonstrated portions of nodules from the adjacent keloid. All cell lines
      were grown under standard conditions with subconfluent cells metabolically
      labeled for radioimmunoassays measuring FN at passage 3 (8 to 9 weeks in culture)
      in the absence and presence of PDGF. Significant differences in production of
      FN/cell and FN/PR/cell between two hypertrophic scars and their matched normal
      skins and for one keloid and its matched normal skin were observed. However, no
      significant difference was observed between the other keloid and AS, nor between
      the other hypertrophic scar and DS. PDGF significantly stimulated FN production
      in 2 of 4 NS cell lines, and in the AS cell line. By FN/cell values, 2 of 5 cell
      lines from the lesions were inhibited and one was increased. In terms of
      FN/PR/cell, 1 of 5 cell lines from the lesions was stimulated and the others
      showed no differences. The mixed results may be attributable to the likelihood
      that the cell lines represent mixed populations. This study demonstrates the
      importance of: 1) histological characterization of all parent tissues from which
      cell lines are derived, and 2) matching cell lines from lesions with cell lines
      from uninvolved normal dermis, in the same individual.

PMID- 22358774
TI  - Ferric cacodylate efficiently stimulates growth of rat renal glomerular
      epithelial cells in vitro.
AB  - Rat renal glomerular epithelial cells (SGE1 cell line) can be maintained and
      grown continuously in serum-free medium supplemented with insulin, iron-saturated
      transferrin (Tr), selenium, bovine serum albumin (BSA), linoleic acid, and
      epidermal growth factor (EGF). Of the growth supplements used, Tr is essential
      for proliferation of the cells. In the present study, we describe the use of a
      unique iron-chelate complex, ferric cacodylate (Fe-Cac), positively charged
      molecules in neutral buffer, that could almost replace Tr in serum-free culture.
      It even stimulated the growth of SGE1 cells more efficiently than ferric chloride
      (FeCl(3)) and other iron-chelate complexes, such as ferric nitrilotriacetate (Fe
      NTA) and ferric citrate (Fe-Cit). The growth-stimulatory activity of Fe-Cac was
      exerted at iron concentrations of more than 0.01 MUg/ml, whereas a 10-fold excess
      of iron concentration was required with FeCl(3), Fe-NTA and Fe-Cit. We observed
      that SGE1 cells grew until confluent, then formed hemicysts (domes) in serum-free
      medium containing Fe-Cac, suggesting that Fe-Cac did not merely permit cell
      growth but also supported polarization and organization of the cells into a
      functional epithelial architecture. Moreover, since the stimulatory activity of
      Fe-Cac was completely abolished by desferrioxamine, a strong iron chelator, it is
      suggested that iron is crucial for growth of SGE1 cells. When the cells were
      treated with suramin, an inhibitor of cellular pinocytosis and endocytosis of a
      large spectrum of ligands including receptor-bound growth factors, growth
      stimulatory activity of Tr was inhibited, whereas the activity of Fe-Cac was not
      affected. These results, taken together, strongly suggest that the growth
      stimulatory activity of Fe-Cac is associated with iron delivery into the cells
      through the cell membrane by diffusion, which is different from Tr receptor
      mediated endocytosis. The use of Fe-Cac for investigating iron-regulated cell
      proliferation is suggested.

PMID- 22358775
TI  - [Surgical management of persistent diarrhea].
AB  - An 82-year-old patient presented with a cervical lesion and refractory diarrhea
      of many years' standing. Surgical therapy of a medullary thyroid carcinoma had
      been performed 16 years previously. Appropriate tumor follow-up had not been
      carried out hitherto. Significantly high levels of calcitonin as well as a
      suspicious octreotide scan indicated late recurrence of the disease. Diarrhea
      ceased following redo surgery.

PMID- 22358776
TI  - [A tongue biopsy led to the diagnosis].
AB  - A 76-year-old patient in otherwise good health presented with a 2-year history of
      bilateral painless submandibular swelling and macroglossia. A standard ENT
      examination revealed no additional symptoms. Tongue biopsy led to the diagnosis
      of amyloidosis, serum immunofixation identified AL amyloidosis and a kappa light
      chain gammopathy resulting from multiple myeloma as the underlying cause.

PMID- 22358777
TI  - [I can hear you, but I don't understand you. Why is it so important to perceive
      high frequencies?].
AB  - The word personality is derived from the Latin word "persona" (mask, person);
      "per sona" means "by the sound or through the sound". In order to look through
      speech, to hear "behind the mask of a person", we have to be able to hear
      properly. Especially the frequencies between 2 kHz and 5 kHz and the overtones
      (the higher we can perceive them, the better) play a central role for decoding
      vowels, consonants and effects of emotions in voice and speech; beyond that they
      provide the perfect enjoyment of music and sound. Obviously they are also a vital
      physical necessity. High frequencies stimulate, they provoke attentiveness and
      concentration. The activity level of the reticular formation is affected by the
      influent of the sensory organs with a crucial role by the hearing sense. Hearing
      in high frequencies leads to higher metabolism, to better motility, to an
      activation of the gamma nervous system and to a better transfer of information.

PMID- 22358778
TI  - [Current status of outpatient surgery in German ENT clinics. Exemplary analysis
      of a university hospital].
AB  - AIM: German ENT clinics currently do not attach great importance to outpatient
      surgical procedures. However, up-to-date data on the proportion of outpatient
      surgeries are not yet available. MATERIALS AND METHODS: In a retrospective study,
      outpatient surgical procedures using anesthesia or sedation at a German ENT
      clinic were analyzed as an illustrative case study. RESULTS: In 2010, the
      proportion of outpatient surgeries performed under anesthesia or sedation in
      relation to the total number of surgeries performed under anesthesia or sedation
      was no more than 3.1%. Although a broad range of surgeries was offered, mainly
      adenoidectomies were carried out. DISCUSSION: In view of the increasingly limited
      financial resources in the German health care system and considering the
      situation in international health care systems, the significance of outpatient
      surgical procedures in ENT clinics is expected to increase in the future. Future
      oriented clinic organization should therefore include sufficient capacity for
      outpatient surgeries. The basic requirement is realistic cost reimbursement by
      the insurers.

PMID- 22358780
TI  - Minimally invasive posterior stabilization for treating spinal tuberculosis.
AB  - We describe a case of dorsal-lumbar vertebral tuberculosis (Pott's disease) first
      treated with antibiotic therapy, bed rest, and cast. After 2 months of treatment
      patient's symptoms worsened. Minimally invasive posterior vertebral stabilization
      was carried out, with excellent clinic and radiographic results.

PMID- 22358783
TI  - Editorial.

PMID- 22358779
TI  - Adherence to routine use of pharmacological prophylaxis of heterotopic
      ossification after total hip arthroplasty: results from an Italian multicenter,
      prospective, observational survey.
AB  - BACKGROUND: In spite of the proven efficacy of pharmacological prophylaxis of
      heterotopic ossification following total hip arthroplasty, its routine use is
      still debated, and no data are available regarding the adherence to its
      administration in clinical practice. MATERIALS AND METHODS: In this prospective,
      observational, multicenter study, 480 consecutive patients operated on for
      primary total hip arthroplasty during the year 2009 were followed
      radiographically for 12 months after surgery in order to assess the incidence of
      periprosthetic heterotopic ossification. Surgeons were free to choose whether to
      administer pharmacological prophylaxis, and were asked to keep a record of the
      duration of the prophylaxis (if used) or the reasons for not using it. To
      facilitate the statistical analysis, all of the participating centers agreed to
      use only one drug (celecoxib) that had already proven to be effective. RESULTS:
      368 patients were administered celecoxib and 112 patients did not receive any
      prophylaxis. Reported reasons for not administering celecoxib prophylaxis were
      the surgeon's opinion that prophylaxis was not needed on a routine basis (84/112
      patients, 75%), previous history of gastrointestinal bleeding (17.8%), and
      concomitant cardiorenal pathologies (7.1%). The overall incidence of heterotopic
      ossification in the celecoxib-treated patients was 23% (no cases of Brooker grade
      3 or 4 ossifications), compared to 55% in the untreated patients (Brooker grade 3
      and 4: 8.9%). Multivariate analysis showed that celecoxib prophylaxis was the
      single most important variable when predicting the occurrence of heterotopic
      ossification. CONCLUSIONS: This study confirms the efficacy and tolerability of
      celecoxib for the prophylaxis of heterotopic ossification after total hip
      arthroplasty, and shows how the surgeon's belief that routine prevention is not
      required still plays an important role in the determination of this complication,
      together with the fear of possible unwanted side effects.

PMID- 22358782
TI  - Surgical management of intra-abdominal cystic lymphangioma. Report of 20 cases.
AB  - BACKGROUND: Cystic lymphangioma (CL) is a benign rare malformation of lymphatic
      vessels. Its discovery in adults is rare. Although it can affect any organ, the
      common forms found in adults are mesenteric and/or retroperitoneal CL. This
      article was designed to study the epidemiological, diagnostic difficulties, and
      therapeutic principles of intra-abdominal cystic lymphangioma in adults. METHODS:
      We report a retrospective study from January 1998 to September 2010 concerning 20
      patients who underwent surgical removal of a CL. We were interested in
      discovering the clinical, biological, and radiological characteristics of CL. The
      localization, size, and number of cysts have been reported, as well as the
      surgical intervention used and the postoperative immediate and late
      complications. RESULTS: The median age was 46 years. Abdominal pain was the main
      symptom and was found in 15 patients (75%). Physical examination revealed an
      abdominal mass in 12 patients (60%). In four patients (20%), the cystic
      lymphangioma was incidental. Abdominal ultrasound and abdominal CT scan helped to
      highlight 22 cystic masses. CL diagnosis was established preoperatively in 13
      patients (65%). Six patients (30%) were operated with a diagnosis other than CL.
      The diagnosis was made intraoperatively in one case (5%). Only two patients (10%)
      were operated on in emergency: one due to an infected CL and the other was CL
      complicated with intracystic hemorrhage. A laparotomy in 13 cases (65%) was the
      surgical approach used, whereas 7 cases (35%) benefited from a laparoscopy. No
      conversion was noted. The majority of the patients, 18 cases (90%), received a
      total cystectomy. Only two patients (10%) had recurrences of which only one was
      reoperated. CONCLUSIONS: The diagnosis of CL often is facilitated by means of
      modern imaging; however, other diagnoses may be discussed, particularly hydatid
      disease endemic areas. If symptomatic lesions or complications arise, complete
      surgical excision, when possible without major sacrifice, seems to be the best
      therapeutic option to reduce the risk of recurrence.

PMID- 22358785
TI  - Key words index.

PMID- 22358787
TI  - Flu papers warrant full publication.

PMID- 22358788
TI  - Turing at 100.

PMID- 22358789
TI  - Over the line.

PMID- 22358790
TI  - The man behind the machine.

PMID- 22358802
TI  - Flu meeting opts for openness.

PMID- 22358803
TI  - Growing pains for children's study.

PMID- 22358804
TI  - Editor's move sparks backlash.

PMID- 22358805
TI  - Extra scrutiny for 'grandee grantees'.

PMID- 22358806
TI  - Physicists raid Tevatron for parts.

PMID- 22358807
TI  - Wild flower blooms again after 30,000 years on ice.

PMID- 22358808
TI  - Turing at 100: Legacy of a universal mind.

PMID- 22358809
TI  - Computer modelling: Brain in a box.

PMID- 22358810
TI  - Turing centenary: The dawn of computing.

PMID- 22358811
TI  - Turing centenary: Life's code script.

PMID- 22358812
TI  - Turing centenary: Is the brain a good model for machine intelligence?

PMID- 22358813
TI  - Turing centenary: Pattern formation.

PMID- 22358814
TI  - Turing centenary: The incomputable reality.

PMID- 22358815
TI  - Neuroscience: Powerful acts.

PMID- 22358819
TI  - Mutant flu: preparing for a pandemic.

PMID- 22358820
TI  - Sugar: there's more to the obesity crisis.

PMID- 22358821
TI  - Mutant flu: assessing biosecurity risks.

PMID- 22358822
TI  - Foreign drug trials: questionable use of chimpanzees.

PMID- 22358823
TI  - Sugar: fruit fructose is still healthy.

PMID- 22358824
TI  - Australia: a case for Aboriginal rangers.

PMID- 22358825
TI  - Sugar: a problem of developed countries.

PMID- 22358826
TI  - Australia: no price on cutting fire risk.

PMID- 22358827
TI  - Australia: better solutions to wildfires.

PMID- 22358828
TI  - Australia: small steps to control invasives.

PMID- 22358829
TI  - Sugar: other 'toxic' factors play a part.

PMID- 22358831
TI  - Astrophysics: First results from Planck observatory.

PMID- 22358830
TI  - Cell biology: Collagen secretion explained.

PMID- 22358832
TI  - Fluid mechanics: Mist opportunities.

PMID- 22358833
TI  - Materials science: Cell environments programmed with light.

PMID- 22358834
TI  - Quantum computing: A topological route to error correction.

PMID- 22358836
TI  - Structural biology: Muscarinic receptors become crystal clear.

PMID- 22358837
TI  - The case for open computer programs.
AB  - Scientific communication relies on evidence that cannot be entirely included in
      publications, but the rise of computational science has added a new layer of
      inaccessibility. Although it is now accepted that data should be made available
      on request, the current regulations regarding the availability of software are
      inconsistent. We argue that, with some exceptions, anything less than the release
      of source programs is intolerable for results that depend on computation. The
      vagaries of hardware, software and natural language will always ensure that exact
      reproducibility remains uncertain, but withholding code increases the chances
      that efforts to reproduce results will fail.

PMID- 22358838
TI  - Experimental demonstration of topological error correction.
AB  - Scalable quantum computing can be achieved only if quantum bits are manipulated
      in a fault-tolerant fashion. Topological error correction--a method that combines
      topological quantum computation with quantum error correction--has the highest
      known tolerable error rate for a local architecture. The technique makes use of
      cluster states with topological properties and requires only nearest-neighbour
      interactions. Here we report the experimental demonstration of topological error
      correction with an eight-photon cluster state. We show that a correlation can be
      protected against a single error on any quantum bit. Also, when all quantum bits
      are simultaneously subjected to errors with equal probability, the effective
      error rate can be significantly reduced. Our work demonstrates the viability of
      topological error correction for fault-tolerant quantum information processing.

PMID- 22358839
TI  - Ubiquitin-dependent regulation of COPII coat size and function.
AB  - Packaging of proteins from the endoplasmic reticulum into COPII vesicles is
      essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm
      in diameter, yet some must increase their size to accommodate 300-400 nm
      procollagen fibres or chylomicrons. Impaired COPII function results in collagen
      deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention
      disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we
      identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat
      formation. CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component
      SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation
      by CUL3-KLHL12 is essential for collagen export, yet less important for the
      transport of small cargo. We conclude that monoubiquitylation controls the size
      and function of a vesicle coat.

PMID- 22358840
TI  - Structural basis of highly conserved ribosome recycling in eukaryotes and
      archaea.
AB  - Ribosome-driven protein biosynthesis is comprised of four phases: initiation,
      elongation, termination and recycling. In bacteria, ribosome recycling requires
      ribosome recycling factor and elongation factor G, and several structures of
      bacterial recycling complexes have been determined. In the eukaryotic and
      archaeal kingdoms, however, recycling involves the ABC-type ATPase ABCE1 and
      little is known about its structural basis. Here we present cryo-electron
      microscopy reconstructions of eukaryotic and archaeal ribosome recycling
      complexes containing ABCE1 and the termination factor paralogue Pelota. These
      structures reveal the overall binding mode of ABCE1 to be similar to canonical
      translation factors. Moreover, the iron-sulphur cluster domain of ABCE1 interacts
      with and stabilizes Pelota in a conformation that reaches towards the peptidyl
      transferase centre, thus explaining how ABCE1 may stimulate peptide-release
      activity of canonical termination factors. Using the mechanochemical properties
      of ABCE1, a conserved mechanism in archaea and eukaryotes is suggested that
      couples translation termination to recycling, and eventually to re-initiation.

PMID- 22358841
TI  - Wetting of flexible fibre arrays.
AB  - Fibrous media are functional and versatile materials, as demonstrated by their
      ubiquity both in natural systems such as feathers and adhesive pads and in
      engineered systems from nanotextured surfaces to textile products, where they
      offer benefits in filtration, insulation, wetting and colouring. The elasticity
      and high aspect ratios of the fibres allow deformation under capillary forces,
      which cause mechanical damage, matting self-assembly or colour changes, with many
      industrial and ecological consequences. Attempts to understand these systems have
      mostly focused on the wetting of rigid fibres or on elastocapillary effects in
      planar geometries and on a fibre brush withdrawn from an infinite bath. Here we
      consider the frequently encountered case of a liquid drop deposited on a flexible
      fibre array and show that flexibility, fibre geometry and drop volume are the
      crucial parameters that are necessary to understand the various observations
      referred to above. We identify the conditions required for a drop to remain
      compact with minimal spreading or to cause a pair of elastic fibres to coalesce.
      We find that there is a critical volume of liquid, and, hence, a critical drop
      size, above which this coalescence does not occur. We also identify a drop size
      that maximizes liquid capture. For both wetting and deformation of the
      substrates, we present rules that are deduced from the geometric and material
      properties of the fibres and the volume of the drop. These ideas are applicable
      to a wide range of fibrous materials, as we illustrate with examples for
      feathers, beetle tarsi, sprays and microfabricated systems.

PMID- 22358842
TI  - Maintenance of muscle stem-cell quiescence by microRNA-489.
AB  - Among the key properties that distinguish adult mammalian stem cells from their
      more differentiated progeny is the ability of stem cells to remain in a quiescent
      state for prolonged periods of time. However, the molecular pathways for the
      maintenance of stem-cell quiescence remain elusive. Here we use adult mouse
      muscle stem cells (satellite cells) as a model system and show that the microRNA
      (miRNA) pathway is essential for the maintenance of the quiescent state.
      Satellite cells that lack a functional miRNA pathway spontaneously exit
      quiescence and enter the cell cycle. We identified quiescence-specific miRNAs in
      the satellite-cell lineage by microarray analysis. Among these, miRNA-489 (miR
      489) is highly expressed in quiescent satellite cells and is quickly
      downregulated during satellite-cell activation. Further analysis revealed that
      miR-489 functions as a regulator of satellite-cell quiescence, as it post
      transcriptionally suppresses the oncogene Dek, the protein product of which
      localizes to the more differentiated daughter cell during asymmetric division of
      satellite cells and promotes the transient proliferative expansion of myogenic
      progenitors. Our results provide evidence of the miRNA pathway in general, and of
      a specific miRNA, miR-489, in actively maintaining the quiescent state of an
      adult stem-cell population.

PMID- 22358843
TI  - Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary
      tumours.
AB  - Since its discovery in the early 1990s the deleted in colorectal cancer (DCC)
      gene, located on chromosome 18q21, has been proposed as a tumour suppressor gene
      as its loss is implicated in the majority of advanced colorectal and many other
      cancers. DCC belongs to the family of netrin 1 receptors, which function as
      dependence receptors as they control survival or apoptosis depending on ligand
      binding. However, the role of DCC as a tumour suppressor remains controversial
      because of the rarity of DCC-specific mutations and the presence of other tumour
      suppressor genes in the same chromosomal region. Here we show that in a mouse
      model of mammary carcinoma based on somatic inactivation of p53, additional loss
      of DCC promotes metastasis formation without affecting the primary tumour
      phenotype. Furthermore, we demonstrate that in cell cultures derived from p53
      deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell
      survival, providing a mechanistic basis for the enhanced metastatic capacity of
      tumour cells lacking DCC. Consistent with this idea, in vivo tumour-cell survival
      is enhanced by DCC loss. Together, our data support the function of DCC as a
      context-dependent tumour suppressor that limits survival of disseminated tumour
      cells.

PMID- 22358846
TI  - Geometry and scale in species-area relationships.
AB  - Arising from F. He & S. P. Hubbell 473, 368-371 (2011). He and Hubbell developed
      a sampling theory for the species-area relationship (SAR) and the endemics-area
      relationship (EAR). They argued that the number of extinctions after habitat loss
      is described by the EAR and that extinction rates in previous studies are
      overestimates because the EAR is always lower than the SAR. Here we show that
      their conclusion is not general and depends on the geometry of habitat
      destruction and the scale of the SAR. We also question their critique of the
      Millennium Ecosystem Assessment estimates, as those estimates are not dependent
      on the SAR only, although important uncertainties remain due to other
      methodological issues.

PMID- 22358844
TI  - Structure and dynamics of the M3 muscarinic acetylcholine receptor.
AB  - Acetylcholine, the first neurotransmitter to be identified, exerts many of its
      physiological actions via activation of a family of G-protein-coupled receptors
      (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five
      mAChR subtypes (M1-M5) share a high degree of sequence homology, they show
      pronounced differences in G-protein coupling preference and the physiological
      responses they mediate. Unfortunately, despite decades of effort, no therapeutic
      agents endowed with clear mAChR subtype selectivity have been developed to
      exploit these differences. We describe here the structure of the G(q/11)-coupled
      M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium
      and identify the binding mode for this clinically important drug. This structure,
      together with that of the G(i/o)-coupled M2 receptor, offers possibilities for
      the design of mAChR subtype-selective ligands. Importantly, the M3 receptor
      structure allows a structural comparison between two members of a mammalian GPCR
      subfamily displaying different G-protein coupling selectivities. Furthermore,
      molecular dynamics simulations suggest that tiotropium binds transiently to an
      allosteric site en route to the binding pocket of both receptors. These
      simulations offer a structural view of an allosteric binding mode for an
      orthosteric GPCR ligand and provide additional opportunities for the design of
      ligands with different affinities or binding kinetics for different mAChR
      subtypes. Our findings not only offer insights into the structure and function of
      one of the most important GPCR families, but may also facilitate the design of
      improved therapeutics targeting these critical receptors.

PMID- 22358847
TI  - Extinction and climate change.
AB  - Arising from F. He & S. P. Hubbell 473, 368-371 (2011). Statistical relationships
      between habitat area and the number of species observed (species-area
      relationships, SARs) are sometimes used to assess extinction risks following
      habitat destruction or loss of climatic suitability. He and Hubbell argue that
      the numbers of species confined to-rather than observed in-different areas
      (endemics-area relationships, EARs) should be used instead of SARs, and that SAR
      based extinction estimates in the literature are too high. We suggest that He and
      Hubbell's SAR estimates are biased, that the empirical data they use are not
      appropriate to calculate extinction risks, and that their statements about
      extinction risks from climate change do not take into account non-SAR-based
      estimates or recent observations. Species have already responded to climate
      change in a manner consistent with high future extinction risks.

PMID- 22358850
TI  - Endogenous musculoskeletal tissue regeneration.

PMID- 22358852
TI  - The chemistry of organoimido derivatives of polyoxometalates.
AB  - The chemistry of organoimido derivatives of polyoxometalates (POMs) has received
      increasing interest. In recent decades, a great development of the synthetic
      chemistry of organoimido derivatives of POMs using different imido-releasing
      reagents has taken place, particularly the novel DCC-dehydrating protocol to
      prepare organoimido derivatives of POMs was developed recently by us and co
      workers. Organoimido substituted POMs as valuable building blocks can construct
      novel nanostructured organic-inorganic hybrid molecular materials in well
      developed common organic synthesis methods, such as Pd-catalyzed carbon-carbon
      coupling and esterification. Therefore, the reactive chemistry of organoimido
      derivatives of POMs stands for the fascinating future of the chemistry of
      organoimido derivatives of POMs.

PMID- 22358849
TI  - Protease-armed bacteria in the skin.
AB  - The skin constitutes a formidable barrier against commensal and pathogenic
      bacteria, which permanently and transiently colonise the skin, respectively.
      Commensal and pathogenic species inhabiting skin both express proteases. Whereas
      proteases secreted by commensals contribute to homeostatic bacterial coexistence
      on skin, proteases from pathogenic bacteria are used as virulence factors,
      helping them colonise skin with breached integrity of the epithelial layer. From
      these initial sites of colonisation, pathogens can disseminate into deeper layers
      of skin, possibly leading to the spread of infection. Secreted bacterial
      proteases probably play an important role in this process and in the deterrence
      of innate defence mechanisms. For example, Staphylococcus aureus proteases are
      essential for changing the bacterial phenotype from adhesive to invasive by
      degrading adhesins on the bacterial cell surface. Secreted staphylococcal
      proteases mediate pathogen penetration by degrading collagen and elastin,
      essential components of connective tissue in the dermis. The activation of the
      contact system and kinin generation by Streptococcus pyogenes and S. aureus
      proteases contributes to an inflammatory reaction manifested by oedema, redness
      and pain. Kinin-enhanced vascular leakage might help bacteria escape into the
      circulation thereby causing possible systemic dissemination of the infection. The
      inflammatory reaction can also be fueled by the activation of protease-activated
      receptors on keratinocytes. Concomitantly, bacterial proteases are involved in
      degrading antimicrobial peptides, disarming the complement system and neutrophils
      and preventing the infiltration of the infected sites with immune cells by
      inactivation of chemoattractants. Together, this provides protection for
      colonising and/or invading pathogens from attack by antibacterial forces of the
      skin.

PMID- 22358853
TI  - Transient gene expression from mammalian cells - a newchapter in animal cell
      technology?A report on the First European Technology Workshop on:Current Status
      and Trends in Mammalian Transient ProteinExpression, Ittingen, Switzerland,
      October 2000.

PMID- 22358851
TI  - Alcohol-related stimuli reduce inhibitory control of behavior in drinkers.
AB  - RATIONALE: Poor behavioral control and heightened attentional bias toward alcohol
      related stimuli have independently received considerable attention in regard to
      their roles in alcohol abuse. Theoretical accounts have begun to speculate as to
      potential reciprocal interactions between these two mechanisms that might promote
      excessive alcohol consumption, yet experimental evidence is lacking. OBJECTIVES:
      The objective of the study was to integrate these two lines of research through
      the development of a novel laboratory task that examines the degree to which
      alcohol cues serve to disrupt mechanisms of behavioral control. METHODS: Fifty
      adult drinkers were recruited to perform the attentional bias-behavioral
      activation (ABBA) task. The ABBA task, an adaptation of traditional cued go/no-go
      tasks, is a reaction time model that measures the degree to which alcohol-related
      stimuli can increase behavioral activation of a drinker and reduce the ability to
      inhibit inappropriate responses. Participants also completed a novel measure of
      attentional bias, the scene inspection paradigm (SIP), that measures fixation
      time on alcohol content imbedded in complex scenes. RESULTS: As hypothesized, the
      proportion of inhibitory failures on the ABBA task was significantly higher
      following alcohol images compared to neutral images. Correlational analyses
      showed that heightened attentional bias on the SIP was associated with greater
      response activation following alcohol images on the ABBA task. CONCLUSIONS: These
      findings suggest that alcohol stimuli serve to disrupt mechanisms of behavioral
      control, and that heightened attentional bias is associated with greater
      disruption of control mechanisms following alcohol images.

PMID- 22358854
TI  - Non-GMP plasmid production for transient transfection in bioreactors.
AB  - We describe a generic plasmid purification process for producing DNA for larger
      scale transient transfection. Data on plasmid quality with regard to residual
      protein, endotoxin content and presence of different plasmid forms is given. The
      effects of contaminants and plasmid forms on expression levels of TNFRp55 and
      SEAP are discussed. Transient transfection of serum-free suspension grown
      mammalian cells represents a suitable approach to provide research quantities of
      proteins (50-100 mg) within1-2 weeks.

PMID- 22358855
TI  - Extraction of plasmid DNA using reactor scale alkaline lysis and selective
      precipitation for scalable transient transfection.
AB  - DNA extracted and purified for vaccination, gene therapy or transfection of
      cultured cells has to meet different criteria. We describe herein, a scalable
      process for the primary extraction of plasmid DNA suitable for transient
      expression of recombinant protein. We focus on the scale up of alkaline lysis for
      the extraction of plasmid DNA from Escherichia coli, and use a simple stirred
      tank reactor system to achieve this. By adding a series of three precipitations
      (including a selective precipitation step with ammonium acetate) we enrich very
      quickly the plasmid DNA content in the extract. The process has been thus far
      used to extract up to 100 mg of plasmid from 1.5 l of clarified lysate,
      corresponding to an E.coli bioreactor fermentation of 3 l.

PMID- 22358856
TI  - Calcium phosphate transfection optimization for serum-free suspension culture.
AB  - Aim of this study was to identify optimal conditions for suspension transfection
      in the absence of serum. Transfection parameters for suspension culture can be
      very different to ones in adherent cells. Most transfection protocols have been
      developed and optimizedfor adherent culture. Using green fluorescent protein
      (GFP) as reporter, FCS was eliminated from the transfection process by altering
      critical parameters and by substituting serum with albumin. Using standard
      phosphate and calcium concentrations for transfection in the absence of serum
      resulted in titers of only 1% of those observed in the presence of serum. A
      reduction of the calcium concentration from 250 mM to 100 mM, yielded a 25-fold
      increase in the expression of the recombinant protein compared to the serum-free
      standard conditions. Altering the phosphate concentration, 1.4 mM in the
      transfection buffer, did not improve the protein expression. Interestingly,
      reduction of DNA quantity by half to a concentration of 0.5 MUg per milliliter of
      culture volume resulted in a two-fold increase of protein production. Addition of
      albumin to serum-free medium protected the cells against the toxicity of the
      calcium phosphate transfection particles (CaPi) yielding higher protein
      expression. All the experiments were executed in a shaken multi-well system,
      allowing high multiplicity parameter screening to speed up optimizations. The
      culture system is inexpensive, simple and efficient, minimizing costs for labor
      and consumables.

PMID- 22358857
TI  - Effects of pCIneo and pCEP4 expression vectors on transient and stable protein
      production in human and simian cell lines.
AB  - To support and meet the demand for recombinant proteins early in the drug
      discovery process, much work has been directed toward improving the methods used
      for transient gene transfection and expression. A factor which could potentially
      affect the outcome of experiments is the choice of the expression vector.
      Conventional vectors such as pCIneo and pcDNA3 have been used frequently. Each of
      these places the gene of interest under the control of the CMV promoter. An
      interesting alternative is provided by episomal vectors. For example, the pCEP4
      vector contains the gene coding for the Epstein Barr nuclear antigen as well as
      the EBNA ori P sequence. This combination allows for the episomal replication of
      the plasmid. In preliminary experiments, we compared transient secreted placental
      alkaline phosphatase production in 8 cell lines from 3 different species using
      the pCIneo vs. pCEP4 vectors and found the utility of the pCEP4 vector to be
      limited to the human 293 EBNA cell line. In this paper, we have compared the two
      vectors in six cell lines of simian and human origin, measuring the transient
      production of secreted placental alkaline phosphatase and human hepatocyte growth
      factor. In general, the pCEP4 vector produced higher amounts of both proteins in
      transient transfections. Results were particularly pronounced in the HEK 293 and
      293 EBNA cell lines. Stable pools of cells (uncloned) expressing human hepatocyte
      growth factor were isolated using pCIneo and pCEP4 and protein production levels
      were compared to those seen in transient transfections. Stable expression with
      pCEP4 was found to produce the highest levels of human hepatocyte growth factor
      in 3 of 4 cell lines. Finally, electroporation and FuGENE(TM)6(Roche,
      Indianapolis IN) as transfection methods were compared measuring transient
      production of secreted placental alkaline phosphatase, human hepatocyte growth
      factor, and green fluorescent protein. FuGENE produced higher protein
      concentrations in less time than electroporation for all 3 proteins.

PMID- 22358858
TI  - Determining subcellular localization of novel drug targets by transient
      transfection in COS cells.
AB  - Genomics-based approaches are increasingly being used to identify disease
      associated genes that represent potential new drug targets. As a first step in
      the validation of genes of unknown function, we describe a method for rapidly
      determining the subcellular localization of the gene product. If an
      immunotherapeutic approach is being considered, it is of particular interest to
      identify targets that are either on the cell-surface or secreted. Transient
      expression in COS cells combined with immunofluorescent staining provides a semi
      high throughput method for determining the subcellular localization of multiple
      targets in parallel. COS cells are ideal for this purpose since: (i) they
      transfect easily; (ii) the high levels of expression that can be achieved
      transiently allow detection after 24 h; and (iii) the relatively large size and
      spread morphology of these cells allows the subcellular organelles to be easily
      visualized. To evaluate the system, we show prototype staining patterns for known
      cytoplasmic,secreted, Golgi-associated, endoplasmic reticulum-associated, and
      plasma membrane proteins, as well as data for novel targets. The localization of
      novel secretory and cell-surface proteins as determined by immunofluorescent
      staining, was confirmed by independent methods.

PMID- 22358859
TI  - Nonviral gene delivery: Towards artificial viruses.
AB  - Several limitations to nonviral gene delivery have been overcome. Small
      nanometric particles have been obtained by condensation ofDNA with a
      polymerizable cation followed by DNA template-directed homopolymerization of the
      vector. Targeting of specific cell types has been achieved by using
      polyethylenimine (PEI), a cationic polymer, coupled to cell ligands such as
      galactose or small RGD peptide that allows cell entry by a receptor-mediated
      endocytosis pathway. Escape of the DNA complexes from the endosomes is favored by
      the 'proton sponge' effect as a consequence of the high buffering capacity of
      PEI. The last barrier to gene delivery, i.e. the nuclear membrane, can be crossed
      at the level of the nuclear pore complexes, by using nuclear localization signal
      DNA molecule conjugates.

PMID- 22358861
TI  - Safety aspects related to recombinant protein expression from Semliki Forest
      virus vectors.
AB  - Semliki Forest virus vectors (SFV) have been developed for efficient transgene
      expression to result in high receptor yields(50-200 pmol receptor/mg protein) in
      a variety of mammalian host cells. Transfer of the SFV technology to mammalian
      cells growing in suspension cultures has made it feasible to produce hundreds of
      milligrams of receptor proteins in a short time. Large-scale production, however,
      raises the questions of the safety of handling virally infected cells for down
      stream processing. Analysis of cell culture medium and SFV-infected cells
      revealed that some infectious particles were still present. Replacement of virus
      containing medium at 2 h post-infection efficiently removed the majority of
      infectious replication-deficient SFV particles. Washes with PBS further reduced
      the number of infectious particles significantly both in the medium and
      associated with cells to levels that allowed safe handling of SFV-infected cells
      outside the cell culture facility for biochemical, pharmacological, or
      electrophysiological assays or down-stream processes in connection to receptor
      purification. Furthermore, engineering of novel temperature-sensitive mutant SFV
      vectors resulted in temperature-controlled transgene expression, which completely
      eliminates the risk of contaminating laboratory personnel.

PMID- 22358860
TI  - New applications of alphavirus-based expression vectors.
AB  - Alphaviruses are positive stranded RNA viruses that replicate to extremely high
      titers. Sindbis and Semliki Forest viral vectors are widely used tools for high
      level production of recombinant proteins. Recent studies have broadened their
      scope to vaccine production, gene therapy, and analysis of cell function. Here we
      discuss the development of non-cytopathic and inducible expression vectors which
      can be applied to bioprocess development strategies. Furthermore, a Sindbis-based
      expression cloning system has been developed that allows for the rapid
      identification of genes encoding proteins with a selected functional activity.

PMID- 22358862
TI  - Authors index.

PMID- 22358864
TI  - Introduction.

PMID- 22358865
TI  - Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres
      composite scaffold in a rabbit model.
AB  - The reconstruction of segmental bone defects remains an urgent problem in the
      orthopaedic field, and bone morphogenetic protein-2 (BMP-2) is known for its
      potent osteoinductive properties in bone regeneration. In this study, chitosan
      microspheres (CMs) were prepared and combined with absorbable collagen sponge to
      maintain controlled-release recombinant human bone morphogenetic protein-2 (rhBMP
      2). The rhBMP-2-loaded composite scaffolds were implanted into 15 mm radius
      defects of rabbits and the bone-repair ability was evaluated systematically. CMs
      were spherical in shape and had a polyporous surface, according to SEM images.
      The complex scaffold exhibited an ideal releasing profile in vitro. The micro
      computed tomographic analysis revealed that the rhBMP-2-loaded composite scaffold
      not only bridged the defects as early as 4 weeks, but also healed the defects and
      presented recanalization of the bone-marrow cavity at 12 weeks. These results
      were confirmed by x-ray. When compared with other control groups, the composite
      scaffold group remarkably enhanced new bone formation and mechanical properties,
      as evidenced by bone mineral content evaluation, histological observations and
      biomechanical testing. Moreover, the biocompatibility and appropriate degradation
      of the composite scaffold could be obtained. All of these results clearly
      demonstrated that the composite scaffold is a promising carrier of BMP-2 for the
      treatment of segmental bone defects.

PMID- 22358866
TI  - Editorial.

PMID- 22358867
TI  - Introduction.

PMID- 22358868
TI  - Haemopoietic growth factors: their role in cell development and their clinical
      use.
AB  - Mature blood cells are derived from haemopoietic stem cells which grow and
      proliferate to give rise to progenitor cells more restricted in their
      proliferation and differentiation capacity. These in turn give rise to cells
      belonging to any of the haemopoietic lineages. The haemopoietic growth factors
      interleukin 3, granulocyte-macrophage colony-stimulating factor, granulocyte
      colony stimulating factor, macrophage colony-stimulating factor and
      erythropoietin act on haemopoietic cells to promote cell survival, proliferation,
      differentiation and maturation, as well as many functions of the mature cells.
      These factors, now purified to homogeneity and molecularly cloned have recently
      become available. This has facilitated studies of their roles in cell production,
      and the range of target cells sensitive to them in vitro and in vivo in several
      species. The latter experimental data led to the first clinical trials where
      these factors have been used successfully in several clinical settings:
      erythropoietin to correct the anaemia of renal disease; granulocyte and
      granulocyte-macrophage colony-stimulating factors to accelerate haemopoietic
      regeneration after chemotherapy and bone marrow transplantation, and in other
      situations where increase in the numbers of white cells and stimulation of their
      function were required. The results to date allow optimism; the clinical use of
      growth factors not only in haematology and oncology, but in wider fields of
      medicine may well constitute a major breakthrough in the near future.

PMID- 22358869
TI  - Hematopoietic growth factor receptors.
AB  - The formation of the cellular constituents of the blood is regulated by a series
      of endogenous polypeptides with largely paracrine function. A number of these
      hematopoietic growth factors (HGF's), which include colony stimulating factors,
      interleukins, and erythropoietin, have been purified to homogeneity and cloned,
      which in turn has led to extensive investigations of their biochemical properties
      and biological effects and functions. The HGF's act on target cells by binding to
      receptors. The kinetics and, to an even larger extent, dynamics of the
      factor/receptor associations display several intriguing characteristics, most of
      which are still poorly understood. Herein, the biochemical characteristics of
      HGF's receptors as well as the binding properties, post-receptor binding events
      and receptor modulation resulting from the association of HGF's and their target
      cells are reviewed.

PMID- 22358870
TI  - The insulin-like growth factor II/mannose-6-phosphate receptor : IGF-II/Man-6-P
      receptor.
AB  - Recent evidence from molecular cloning, biochemical and immunological experiments
      has established that the cation-independent mannose-6-phosphate (Man-6-P)
      receptor and insulin-like growth factor-II (IGF-II) receptor are the same
      protein. Although the role of the IGF-II/Man-6-P receptor as a transporter of
      hydrolytic enzymes in the biogenesis of lysosomes is certain, elucidation of the
      receptor's structure has not yet provided major insights into the function of IGF
      II binding. Mutually exclusive binding of IGF-II and naturally occurring
      phosphomannosyl ligands to distinct but proximal sites on the receptor suggests
      that the IGF-II/Man-6-P receptor cannot simultaneously fulfill the functional
      requirements of both IGF-II and lysosomal enzymes. Does the receptor transduce on
      intracellular signal in order to mediate the biological effects of IGF-II? If so,
      then the receptor must interact with an effector molecule, perhaps a G protein,
      in the mechanism of IGF-II action. Further information from ligand binding and
      especially mutagenesis experiments will be needed to elucidate the potentially
      multiple functions of the IGF-II/Man-6-P receptor.

PMID- 22358871
TI  - Transforming growth factor-beta receptors.
AB  - Transforming growth factor beta (TGF-beta) binds specifically and with high
      affinity to several different cell surface proteins. Low M(r) proteins of 50,000
      and 80,000 have been termed type I and type II receptors. Intermediate sized
      binding components of 115,000-140,000 M(r) and a high binding components of
      approximately 250,000 M(r) in subunit size have been termed type III receptors.
      The high M(r) component is a proteoglycan containing the glycosaminoglycan chains
      of heparan sulfate and chondroitin sulfate and the intermediate sized components
      are its core proteins. Although almost all cells have TGF-beta receptors, binding
      of TGF-beta to the type III binding components is restricted to cells of
      fibroblastic, osteoblastic and chondroblastic origin. The physiological relevance
      of each individual binding class is unclear. However, recent data indicate that
      the type III protein does not transmit signals to inhibit cell proliferation,
      induce protein synthesis, or promote cytomorphological change and that these
      activities may be mediated through the type I receptor. The mechanism of signal
      transduction remains unknown, but it does not appear to be associated with
      tyrosine phosphorylation or phosphorylation of the 40s ribosomal protein S6.

PMID- 22358872
TI  - Transforming growth factor-betas as modulators of pericellular proteolytic
      events.
AB  - Since the discovery of transforming growth factor-beta:s an increasing number of
      different biological effects have been attributed to this group of proteins.
      Analysis of the cellular responses to TGFbeta stimulation at the molecular level
      has indicated that TGFbeta acts as an activator of transcription of several
      genes. This may in part explain the plethora of various functions that have been
      ascribed to TGFbeta. In addition to the TGFbeta family of polypeptides there is
      an increasing number of related factors, whose major roles appear to be involved
      in developmental processes. A distinct feature of TGFbeta is its ability to
      regulate pericellular proteolysis of cultured cells. As yet this property has not
      been associated with other members of this group of polypeptides. Depending on
      the target cell type TGFbeta may either increase or decrease pericellular
      proteolytic activity. Proteolytic activation of latent TGFbeta and its possible
      inhibition by TGFbeta-induced protease inhibitors could be a physiological feed
      back mechanism in the control of proteolytic activity in the vicinity of cells.

PMID- 22358873
TI  - Recent developments in the structure, function and regulation of platelet-derived
      growth factor and its receptors.
AB  - Recent evidence strongly suggests that production of platelet-derived growth
      factor (PDGF) is regulated by several mechanisms, including noncoordinate
      expression of the PDGF A- and B-chain genes, alternative transcript splicing,
      differential mRNA stability, and translational control. Considerable progress has
      also been made in our understanding of PDGF receptors. Recent studies demonstrate
      that there are two distinct PDGF receptor genes. PDGF receptors can undergo
      dimerization and it has been postulated that dimerization can lead to the
      formation of three different receptor dimers. In addition, it appears that
      dimerization is required for activation of PDGF receptors and the biological
      activity of PDGF. Although relatively little is known about the regulation of
      PDGF receptors, PDGF receptors are known to be down regulated by PDGF, and
      expression of PDGF receptors begins relatively early during embryogenesis.
      Furthermore, the binding of PDGF is regulated by cell density. Unexpectedly,
      recent evidence suggests that PDGF can localize to the nucleus, which suggests an
      intranuclear function for PDGF may exist. Together, these findings imply a
      complex and multi-leveled regulatory scheme for controlling the production of
      PDGF and its receptors.

PMID- 22358875
TI  - Adaptive fuzzy control of nutrients concentration in fed-batch culture of
      mammalian cells.
AB  - An adaptive fuzzy controller was developed to control the glucose and glutamine
      concentrations in the reactor constant at the desired level. The parameter values
      of the controller change during the cultivation according to the culture phase
      which was detected by the lactate concentration. Cultivations with different
      glucose and glutamine set point concentrations of a recombinant BHK anchorage
      dependent cell line were performed in a fed-batch reactor on-line connected with
      an HPLC system. Glucose and glutamine concentrations were satisfactorily
      controlled at each set point during all cultivation periods. Ammonia had a
      determining effect on productivity since it inhibited cell growth and protein
      specific production. Ammonia production increased with an increase of glutamine
      or a decrease of glucose set point concentrations, indicating the importance of
      glucose to glutamine ratio for the optimization of productivity in mammalian cell
      cultures.

PMID- 22358876
TI  - Reinforcing apoptosis-resistance of COS and myeloma cells by transfecting with
      bcl-2 gene.
AB  - COS, myeloma and HeLa cells, which are commonly used for protein production by
      cell culture, were transfected with human bcl-2 gene encoded on the shuttle
      vector BCMGS. Expression of human bcl-2 improved survival of cells remarkably,
      mildly, or negligibly for COS, myeloma, and HeLa, respectively. Four clones were
      obtained from the human bcl-2 expressing cell population of COS cells. They
      expressed human bcl-2 almost at the same level. The viable cell numbers were 6,
      2.5, 2.5, and 0.8 times as many for the clones #8, #5, #6, and #7, respectively,
      as for the control COS cells, when they were cultured at low (0.2%) serum
      concentration for 9 days. The bcl-2 overexpressing COS cells showed morphology
      different from that of the control COS cells in serum limited condition. When
      transfected with mouse lambda protein gene carried by an SV40-derived vector,
      clone #8 of the bcl-2 transfected COS cells continued the transient expression of
      lambda protein longer than the control COS cells.

PMID- 22358874
TI  - Heparin-binding growth factors and their receptors.
AB  - Heparin-binding growth factors modulate diverse biological activities including
      cellular proliferation, cellular differentiation, morphogenesis, and
      angiogenesis. Biochemical characterization for two members of the heparin-binding
      growth factor family, acidic and basic fibroblast growth factors, is extensive,
      while characterization of the remaining five members is forthcoming. Cell surface
      receptors have been identified for acidic and basic fibroblast growth factors,
      but little is known concerning their sites of action in vivo or the mechanisms
      involved in transducing the energy of growth factor binding to a biological
      response. An understanding of the biological basis for the diversity of the
      heparin binding growth factor family and the in vivo actions of these factors
      will prove a major challenge to future research efforts.

PMID- 22358877
TI  - Evaluation of the serum-free medium MDSS2 for the production of poliovirus on
      vero cells in bioreactors.
AB  - The serum-free medium MDSS2 (Merten et al., 1994), was used for cultivating Vero
      cells as well as for producing poliovirus (Sabin type 1) in static and in
      perfused micro-carrier cultures. At slightly different growth rates of 0.0120/h
      and 0.0106/h, respectively, static cultures in serum-containing (SCM) and serum
      free (SFM) medium produced titers of (106.75) and 10(6.67) TCID50 per 50 ul;
      signifying a specific productivity of 0.89 and 1.07 TCID50/c.Serum-free
      bioreactor cultures of Vero cells on DEAE-dextran microcarriers at 6.25 g/l
      produced cell densities of about 1.5*10(6)c/ml. After infection with virus
      (multiplicity of infection (MOI) 0.1-0.3) titers of about 6.3*10(8) TCID50/ml
      were obtained, signifying an average specific productivity of 7.1 TCID50/c.h.
      Although these values were 4 and 2 fold, respectively, higher than in classical
      resum-based production processes (Montagnon et al. Dev. biol. Stand. 1981, 47,
      55), a reference culture, for which cell growth was done in SCM and only virus
      production was done in SFM, produced 2*10(9) TCID/ml with an average specific
      virus production rate of 18.9 TCID50/c.h. The differences between the fully serum
      free and our reference process were mainly due to physiological differences of
      cells grown in SCM and SFM and also due to strongly modified consumption kinetics
      after virus infection leading to limitations of one or several essential medium
      compounds, like glucose and amino acids. Avoiding these limitations by increasing
      the residual concentration of glucose, glutamine, histidine, and SH-amino acids,
      led to specific virus production rates (of about 17.9 TCID59/c.h.) comparable to
      those found in the reference virus production process. The optimisation of the
      production of the poliovirus (Sabin 1) will be described with respect to the
      modification of the medium composition.

PMID- 22358878
TI  - Surfactant-mediated gene transfer for animal cells.
AB  - A commercially available cationic surfactant, dimethyl-dioctadecyl ammonium
      bromide (DDAB), was used for making lipid vesicles. DDAB easily dissolved in
      water at 60  degrees C and formed lipid vesicles at room temperature. The lipid
      vesicles showed very low cytotoxicity compared with other cationic surfactants.
      After the lipid vesicles were mixed with plasmid DNA solution, the solution was
      added to mammalian cells. The addition of a nonionic surfactant (Tween 80) to the
      cationic lipid vesicles at the weight ratio of 1:1 enhanced transfection
      efficiency. Adding more or less than the optimal amounts of DNA and lipid
      vesicles resulted in decreased transfection efficiency. With the optimal amounts
      of DNA (pCMVbeta) and lipid vesicles, about 90-95% of CHO-K1 and BHK-21C13 cells
      transiently expressed beta-galactosidase activity 24 h after transfection. By
      this procedure, stable transformants around 10(5) cells corresponding to 10%
      efficiency could be obtained by one batch transfection.

PMID- 22358879
TI  - Efficient and inducible production of human interleukin 6 in Chinese hamster
      ovary cells using a novel expression system.
AB  - High level and inducible production of human interleukin 6 (hIL-6) was achieved
      using a novel expression system in Chinese hamster ovary (CHO) cells. In this
      system, the transcription of hIL-6 gene under the control of PhCMV*-1 promoter
      composed of tetracycline operator sequences and a minimal promoter is activated
      by a chimeric transactivator (tTA) composed of tetracycline repressor and
      transactivating domain of VP16 protein of herpes simplex virus. The transcription
      of tTA gene, which is also under the control of PhCMV*-1 promoter, is activated
      by itself via a positive feedback cycle. The expression of both genes is further
      enhanced by potentiating the VP16 transactivating domain of tTA transactivator
      with pX protein of hepatitis B virus. In the presence of tetracycline, the tTA
      transactivators can not bind to PhCMV*-1 promoter, therefore, the expression of
      hIL-6 and tTA gene is suppressed, and the pX will not activate basal
      transcription. In the absence of tetracycline, tTA transactivators bind to PhCMV*
      1 promoter and activate efficient transcription of hIL-6 and tTA gene, and the
      transcription is further enhanced by pX via VP16 transactivating domain. Using
      this strategy, we isolated a clone (UX1) producing hIL-6 at a rate about 1425
      ng/10(6) cells/day. Furthermore, the hIL-6 production is stringently regulated by
      tetracycline. This results suggested a novel strategy to establish highly
      efficient, inducible and cell type independent recombinant protein production
      system by using an artificial promoter to recruit transactivators and
      coactivators which can synergistically activate transcription.

PMID- 22358880
TI  - Structure and expression of integrated hepatitis B virus genes in an HBs antigen
      producing human cell line (huGK-14).
AB  - A human continuous cell line (huGK-14) within a lineage of passaged cultures was
      investigated in the mode of integration and expression of hepatitis B virus (HBV)
      genes. HBV DNA was integrated in eight different sites of the cellular DNA, in
      each of which HBV genome was rearranged, fragmented, and/or partly deleted.
      Complete HBV genome that may lead to production of infectious virus particles was
      not detected in the cells nor in the culture medium. Clones of cDNA containing a
      complete coding frame for small HBs antigen protein (type adr) were obtained from
      mRNA of the cells. The cells were stable over the period of six months of
      cultivation and more than 60 population doublings in the mode of HBV integration
      and HBs mRNA expression.These results provide substantial evidence for the
      absence of an ability for the integrated DNA to create an infectious product in
      the cell; for the stable production of HBs mRNA from the cells, and suggest the
      usefulness of this cell line as a substrate for HBV vaccine production.

PMID- 22358881
TI  - Effect of hypoxia duration on the oxygen-dependent production of a recombinant
      protein, beta-galactosidase, by an animal cell line, F6D2, with a hypoxia
      inducible enhancer.
AB  - Expression of specific genes is a strategy of animal cells for adaptation to
      oxygen deficiency and the mechanism underlying the hypoxic activation of gene
      expression may be useful for efficient production of recombinant proteins by
      animal cells, because oxygen is a limiting factor in animal cell cultures. We
      prepared an animal cell line harboring the plasmid in which expression of a
      reporter gene, beta-galactosidase, is controlled by an enhancer responsible for
      the hypoxic activation of gene transcription. The purpose of this paper is to
      understand this hypoxic production of recombinant proteins quantitatively by a
      mathematical model originally developed based on the following hypotheses; 1 lacZ
      (the reporter gene) is transcribed after HIF-1 protein complex is bound to the
      hypoxic enhancer, 2. beta-galactosidase synthesis rate is limited at the
      transcription of lacZ, 3. HIF-1 is an inactive form under a normal oxygen
      concentration, 4. Oxygen works as a repressor in the synthesis of HIF-1 protein,
      5. Both beta-galactosidase and HIF-1 are decomposed according to the first order
      reaction. The effects of hypoxic duration as well as oxygen concentration on the
      beta-galactosidase production were successfully predicated by the model.

PMID- 22358882
TI  - Erythropoietin enhancer stimulates production of a recombinant protein by Chinese
      hamster ovary (CHO) cells under hypoxic condition.
AB  - Oxygen is a limiting nutrient in animal cell culture and its supply is still
      worthy of improvement for production of useful proteins with a high efficiency.
      From a different point of view, development of the system by which a high
      productivity can be maintained even under hypoxic condition as well as under
      normoxic condition may be important. A number of hypoxia-inducible genes have
      been found in eucaryotic cells and the induction in most cases, if not all, is
      due to hypoxic activation of the gene transcription. Transcription of
      erythropoietin gene is highly hypoxia-inducible and the induction is achieved by
      binding of a protein, which is widely distributed in animal cells, to a short DNA
      stretch (erythropoietin enhancer) in the 3' flanking region of erythropoietin
      gene. Using a hepatoma cell line (Hep3B) that produces the endogenous
      erythropoietin in an oxygen-dependent manner and Chinese hamster ovary cells that
      have been widely used for production of recombinant proteins, we show that, under
      hypoxic condition, the erythropoietin enhancer can activate not only the promoter
      of erythropoietin gene but also promoters of cytomegalovirus early genes and
      eucaryotic polypeptide chain elongation factor gene, both of which are very
      active in animal cells under normoxic condition.

PMID- 22358883
TI  - Oral administration of antigen does not influence the proliferation and IFN-gamma
      production of responsive CD8+ T cells but enables to establish T cell clones with
      different lymphokine production profile.
AB  - Feeding of a whole casein diet, which abolished the alpha(s1)-casein-specific
      proliferation and IFN-gamma productivity of CD(4+) T cells, did not affect the
      proliferative response of CD8(+) T cells with regard to the antigen dose
      response, cell dose response, kinetics of the proliferation and epitope
      specificity, as well as IFN-gamma production. To assess the characteristics of
      the CD8(+) T cells, we established alpha(s1)-casein-specific CD8(+) T cell clones
      from both casein-fed and control mice. The established clones produced different
      amount of IFN-gamma and IL-10, and one clone derived from the casein-fed mice
      produced a remarkable amount of IL-10. The clones from casein-fed mice produced
      considerable amounts of TGF-beta, while those from control mice produced only
      small amounts. The possible role of CD8(+) T cells in oral tolerance is
      discussed.

PMID- 22358885
TI  - Concanamycin A, a vacuolar type H(+)-ATPase inhibitor, induces cell death in
      activated CD8(+) CTL.
AB  - Concanamycin A (CMA) and concanamycin B (CMB) are specific inhibitors of vacuolar
      type H(+)-ATPase (V-ATPase). In our previous studies, intraperitoneal injection
      of CMB was shown to suppress the increase in CD8(+) CTL population, but not to
      affect CD4(+) and B220(+) populations, in mice immunized with allogeneic tumors.
      To clarify the molecular basis of the selective decrease in the CD8(+) CTL
      population by CMB, we have performed a series of in vitro experiments with use of
      CMA. Cell viability of the CD8(+) population prepared from the immunized mice was
      preferentially decreased by CMA treatment. Moreover, in the CD8(+) CTL clone, CMA
      induced a marked DNA fragmentation and nuclear condensation characteristic of
      apoptosis. Anti-CD3 or phorbol ester accelerated the CMA-induced reduction in
      cell viability of the CD8(+) CTL clone, but not CD4(+) T cell clones. However,
      this rapid cell death was not accompanied by DNA fragmentation and nuclear
      condensation. Perforin and granzyme B were unlikely to be involved in such cell
      death. Thus, our data suggest that V-ATPase activity is essential for survival of
      CD8(+) CTL especially when activated.

PMID- 22358886
TI  - Multilayer rat hepatocyte aggregates formed on expanded polytetrafluoroethylene
      surface.
AB  - Feasibility of using a macroporous membrane material, expanded
      polytetrafluoroethylene (ePTFE), for culturing hepatocytes on its surface was
      examined. Adult rat hepatocytes were attached to an ePTFE surface and cultured in
      a hormonally defined medium supplemented with or without fetal calf serum (FCS,
      10%) or bovine serum albumin (BSA, 0.03-3%). When cultured in a FCS-suplemented
      medium, hepatocytes reorganized themselves into multilayer cell aggregates on an
      ePTFE surface. The morphological characteristics of hepatocytes were influenced
      by the modification of the ePTFE surface as well as the culture medium.
      Hepatocytes cultured on a polyvinylalcohol (PVA)-coated ePTFE surface formed many
      more multilayer cell aggregates than those cultured on an uncoated ePTFE surface.
      Such highly multilayered hepatocyte aggregates were also noted when the cells
      were cultivated in a BSA-supplemented medium. On the other hand, when cultured in
      a FCS- or BSA-free medium, hepatocytes formed cell monolayers on both PVA-coated
      and uncoated ePTFE surfaces as did the cells on a collagen-coated polystyrene
      surface. The hepatocytes in the aggregates exhibited high albumin expression
      capability and low DNA synthesis rate as compared with those in monolayer
      cultures. The multilayer hepatocyte aggregates, as immobilized on a PVA-coated
      ePTFE surface in a serum-supplemented medium, are shown to be not only
      morphologically, but functionally differentiated, and will provide us a model
      system for the development of a bioreactor using hepatocytes, particularly for a
      hybrid-type artificial liver.

PMID- 22358887
TI  - Improvement of antigen binding ability of human antibodies by light chain
      shifting.
AB  - Human HB4C5 hybridoma cells produce a lung cancer-specific IgM human monoclonal
      antibody (mAb). HB4C5 human mAb cross-reacts with Candida cytochrome c (Cyt c)
      and carboxypeptidase (Cpase). Concanavalin A (ConA)-resistant variants of HB4C5
      cells loss the original light chain followed by expression of various new light
      chains at a high incidence (light chain shifting) (Tachibana et al., 1996). HTD8
      cells, one of the ConA-resistant variant subclones of HB4C5 cells, undergo the
      active light chain shifting and produce various sublines, each of which stably
      secretes new mAb consisting of a new light chain and a HB4C5 heavy chain. The new
      mAb exhibits altered antigen binding ability from that of the original antibody.
      We could expect that HTD8 cells can be used as 'a light chain stem cell line' to
      improve antigen binding ability and specificity of established human mAbs. A
      BD9D12 IgG human mAb recognizes lung cancer cells and cross-reacts with
      cytokeratin 8. Introduction of the heavy chain gene of BD9D12 mAb into HTD8 cells
      resulted in establishment of various sublines which secreted various kinds of
      hybrid antibodies consisting of different light chains derived from HTD8
      subclones which underwent light chain shifting and a common IgG heavy chain
      derived from BD9D12. These hybrid antibodies exhibited different or improved
      reactivities to Cyt, Cpase, cytokeratin 8 and various cancer cells from those of
      parental mAb, demonstrating that light chain shifting can be applied to improve
      the affinity and specificity of human mAb.

PMID- 22358888
TI  - Physical and biological studies on DNA/anti-DNA immune complex formed in vitro.
AB  - In vitro preparation of DNA/anti-DNA immune complex using monoclonal antibody and
      low molecular weight homogeneous DNA was described and the characteristics of the
      immune complex were identified. The immune complex was formed by the monoclonal
      antibody with DNA effectively at high ratios of antibody/DNA. The activation and
      binding ability of the immune complex to the complement was considerably high,
      whereas the capacity to bind red blood cells via C3b complement component
      receptor was shown relatively low. The assay of sucrose density gradient
      ultracentrifugation indicated that the sedimentation coefficient of the immune
      complex was between 10S and 23S. Studies of organ distribution and uptake of IC
      demonstrated a particular affinity to the kidney tissue. The significance of
      these results with respect to the latent pathogenicity of the immune complex was
      discussed.

PMID- 22358889
TI  - Potential molecular chaperones involved in laminin chain assembly.
AB  - To explore potential molecular chaperones involved in the intracellular assembly
      of laminin chains, bovine aortic endothelial cells were treated with a thiol
      cleavable divalent cross-linking reagent, dithio-bis-(succinimidylpropionate),
      and cellular proteins cross-linked to laminin chains were co-immunoprecipitated
      with anti-laminin antiserum. Sodium dodecylsulfate (SDS) gel electrophoresis of
      the precipitate under reducing condition showed polypeptides with estimated sizes
      of 80, 60 and 50 kDa together with laminin chains. Two dimensional
      electrophoresis, in which non-reducing and reducing SDS electrophoresis were
      combined, suggested that many molecules of these polypeptides were cross-linked
      to each laminin chain. Sepharose CL-4B beads conjugated with E8 fragment of mouse
      laminin-1 was prepared. Affinity chromatography with the beads of microsomal
      proteins from rat liver showed that Bip and HSP70 associated to laminin chains
      and dissociated upon ATP hydrolysis. Protein-disulfide isomerase also showed
      affinity to the column. GRP94 and calnexin showed strong affinity and were washed
      out only with a detergent solution. Thus, many molecular chaperones are suggested
      to be involved in the intracellular assembly of laminin chains.

PMID- 22358890
TI  - Biological response of endothelial cells and its modulation by cytokines:
      prospects for therapy and bioprocesses.
AB  - Endothelial cells are involved in important pathological situations. They could
      be the target for infectious processes as for example in Cowdriosis, an important
      disease in cattle due to the rickettsia Cowdria ruminantium prevalent in the
      south of the Sahara. They are also connected to angiogenic processes related to
      tumor invasion.Our results indicate that AIDS related Kaposi sarcoma cells may be
      of endothelial origin. We conclude from our data the mobility of those cells,
      related to the expression of the metalloproteinases (especially the 92 kD form of
      the enzyme), is an important factor in Kaposi saroma dissemination and is the
      main factor limiting the scale up of Cowdriosis vaccine production in Bovine
      Umbilical Endothelial Cell line. We showed that PMA and TNF increased the 92 kD
      Metallaproteinase and that TGFbeta, produced in an inactive form in cultures of
      Human Umbilical Vein Endothelial Cells, is a potential inhibitor of Kaposi
      sarcoma spreading, and could also be useful in improving our process for Cowdria
      ruminantium vaccine production, since it reduces the sensitivity of the cells to
      mechanical stress without affecting significantly the overall infectious process.

PMID- 22358891
TI  - Mannosylerythritol lipid induces granulocytic differentiation and inhibits the
      tyrosine phosphorylation of human myelogenous leukemia cell line K562.
AB  - Mannosylerythritol lipid (MEL), which induced granulocytic differentiation of
      human promyelocytic leukemia cell line HL60, also induced differentiation of
      human myelogenous leukemia cell line K562. MEL inhibited insulin-dependent cell
      proliferation and induced leukocyte esterase activity of K562 cells. MEL markedly
      increased the differentiation-associated characteristics in granulocytes, such as
      nitroblue tetrazolium (NBT) reducing ability, expression of Fc receptors, and
      phagocytic activity of K562 cells. The tyrosine phosphorylation in K562 cells
      inhibited by MEL. These results suggest that MEL directly down-regulates the
      tyrosine kinase activities in K562 cells to inhibit the cell proliferation and to
      induce the differentiation.

PMID- 22358892
TI  - Anti-carcinogenic activity of 6-methylsulfinylhexyl isothiocyanate-, an active
      anti-proliferative principal of wasabi (Eutrema wasabi Maxim.).
AB  - Synthetic 4-methylsulfinylhexyl isothiocyanate (MITC)(a potent inducer of phase 2
      detoxification enzymes from broccoli) and 6-MITC(a potent anti-proliferative
      principal from wasabi) slightly inhibited the induction of mouse skin tumor in a
      two-stage process of carcinogenesis (initiator, 9,10-dimethyl-1,2-benzanthracene;
      promotor,12-o-tetradecanoylphorbol-13-acetate), but the effect was not
      significant. Both compounds, however, significantly inhibited the mutation of
      skin resulting from topical applications of the carcinogens. When a murine
      hepatoma cell line, Hepa 1c1c7, was treated with 2-,4-,6- and 8-MITCs, they
      augmented the induction of its quinone reductase, one of the phase 2
      detoxification enzymes in a concentration dependent manner, and the 4- and 6
      MITCs were much more potent on the reduction of the enzyme than the 2- and 8
      MITCs. All 2-, 4-, 6- and 8-MITCs suppressed the growth of murine tumor cells,
      their suppressive activities being proportional to the length of their methyl
      residue. They were also cytotoxic to mouse peritoneal exudate macrophages which
      were not proliferating in vitro, indicating that the cellular targets of
      isothiocyanate may not be dependent upon the cell cycle. In addition, all the 2-,
      4-, 6- and 8-MITCs inhibited the production of nitric oxide (a potent radical
      carcinogen) by peritoneal macrophages.

PMID- 22358893
TI  - Immunomodulating activities of polysaccharide fractions from dried safflower
      petals.
AB  - In the course of screening for immunomodulators, we found a significant
      blastogenic activity specific for splenic B cells in the extracts of safflower
      (Carthamus tinctorius L.). Active fractions termed SF1 and SF2 were purified from
      dried petals of safflower by boiling water extraction, ethanol precipitation and
      Sepharose CL-2B column chromatography. The elution profiles of the gel filtration
      indicated that the molecular weight of SF1 and SF2 was estimated to be more than
      100 kD. Major components of SF1 and SF2 seem to be polysaccharides, and
      structural analysis of alditol acetate derivatives by GC-MS revealed some
      differences between SF1 and SF2 in the sugar component. Biological activities of
      SF1 and SF2 on B cells and macrophages were examined in comparison with
      lipopolysaccharides (LPS). SF1 and SF2 induced both the proliferation and the IgM
      production of B cells to the equivalent level as those induced by LPS. In
      macrophages, SF1 and SF2 effectively stimulated the production of NO. However,
      SF1 stimulated the production of IL-1, IL-6, and TNF as much as LPS, while SF2
      induced them only weakly or not at all. Thus, these results suggest that SF1 and
      SF2 activate B cells and macrophages in different mechanisms.

PMID- 22358894
TI  - Selective cytotoxicity of marine algae extracts to several human leukemic cell
      lines.
AB  - Extracts from 8 species of marine algae which showed selective cytotoxicity in
      our previous screening program, were further examined for cytotoxic spectra to
      five human leukemic cell lines. The extract from a red alga, Amphiroa zonata
      exhibited strong cytotoxicity to all human leukemic cell lines tested and murine
      leukemic cells L1210 at the final concentrations from 15 to 375 ug ml-(1). Then
      the cytotoxicity was not found in normal human fibroblast HDF and murine normal
      cells NIH-3T3. The active extract fraction from this alga was soluble in higher
      polar organic solvents and water and heat-stable. The extract from a brown alga
      Dilophus okamurae with weak selective cytotoxic activity to L1210 cells exhibited
      not only strong cytotoxicity to L1210, but also to human leukemic cells, HL60 and
      MOLT-4 at 50 ug ml-(1). While, the extract from a green alga, Cladophoropsis
      vaucheriaeformis with most selective cytotoxic activity, did not show
      cytotoxicity to any human leukemic cell lines tested at 50 ug ml-(1). However,
      this extract showed strong cytotoxicity to two human leukemic cell lines and NIH
      3T3 at 100 ug ml-(1). Thus, it was considered that a red alga, Amphiroa zonata
      might be suitable natural source for development of anti-cancer agents without
      side-effect.

PMID- 22358895
TI  - Inhibitory effect of serum from rats administered with coffee on the
      proliferation and invasion of rat ascites hepatoma cells.
AB  - The action of coffee on the proliferation and invasion of a rat ascites hepatoma
      cell line of AH109A was investigated using in vitro and ex vivo assay systems.
      When rats were given oral intubation of instant coffee powder solution, the sera
      of those rats had the potent inhibitory activity on both the proliferation and
      invasion of AH109A. The activity of rat serum was both time- and dose-dependent.
      The instant coffee powder also inhibited the proliferation and invasion of AH109A
      in vitro. These results indicate that coffee has anti-proliferative and anti
      invasive activity both in vitro and ex vivo. They also suggest that some anti
      proliferative and anti-invasive material(s), which may be the ingredient(s) of
      coffee or their metabolites, appear in rat serum when rats are given oral
      intubation of coffee, although a possibility that host defense systems may be
      activated by the oral intubation of coffee cannot be ruled out.

PMID- 22358896
TI  - Concentrating Autographa californica nuclear polyhedrosis virus and recombinant
      alkaline phosphatase from insect cells using a temperature-sensitive hydrogel.
AB  - Recombinant alkaline phosphatase expressed in insect cells was concentrated by a
      factor of one and half times at a separation efficiency of 54.2% using hydrogel
      ultrafiltration. Enzyme concentration was confirmed by SDS-PAGE as well as by
      spectrophotometric measurement. Wild and recombinant Autographa californica
      nuclear polyhedrosis viruses (AcNPV) were concentrated 1.4 and 1.6 times of the
      feed solution at 48.5 and 60.0% separation efficiency, respectively. Hydrogel
      ultrafiltration appears to be an attractive alternative for the concentration of
      AcNPV and recombinant proteins from insect cells.

PMID- 22358897
TI  - Enhancement of cytokine expression in transiently transfected cells by
      magnetoliposome mediated hyperthermia.
AB  - We investigated the enhancement of cytokine expression by heat treatment in
      transiently transfected glioma cells. The cells were transfected with plasmid
      bearing the interferon (IFN)-beta gene under control of the MMTV promoter, which
      is inducible by glucocorticoid (dexamethasone). Then magnetite particles (10 nm
      diameter) as intracellular heating material were incorporated to the cells as the
      form of magnetoliposome. After 5 hours of incorporation, alternative magnetic
      field (384Oe, 118kHz) was applied for intracellular heating. IFN-beta secreted in
      the medium was assayed and its concentration was compared to the extracellular
      heating induced expression, both in the presence and absence of dexamethasone.
      Higher IFN-beta concentration was detected in intracellular heating even at lower
      temperature, 39  degrees C, than 43  degrees C in extracellular heating. The IFN
      beta expression level reached in the presence of dexamethasone was about three
      times higher than in the absence of inducer. In intracellular heating of 60 min,
      the surviving cell number reduced until 20%.

PMID- 22358898
TI  - Preparation of recombinant six-histidine-tagged human LECT2, a chemotactic
      protein to neutrophils, in Escherichia coli.
AB  - LECT2 is a chemotactic protein to neutrophils. A recombinant six-histidine-tagged
      human LECT2, (His)(6)-LECT2, was expressed in E. coli using a pET21a(+) vector.
      The (His)(6)-LECT2 was purified from the soluble fraction in E. coli as a single
      band in sodium dodesyl sulfate/polyacrylamide gel electrophoresis using three
      steps of column chromatography with Ni(2+)-charged nitrilo-triacetic acid (Ni
      NTA) agarose, DEAE-Sepharose, and CM-Sepharose. The purified (His)(6)-LECT2 was
      yielded with 96 ug from the soluble fraction of 1,500 ml culture of E. coli. The
      circular dichroism spectrum of (His)(6)-LECT2 showed the folded structure, which
      is rich in beta-sheet structure and rare in alpha-helix.

PMID- 22358899
TI  - In vitro promoting activity of human interferon beta production by extracts of
      marine algae from Japan.
AB  - Two hundreds species of marine algae were investigated for in vitro promoting
      activity of human interferon beta (IFN-beta) production by poly(I:C)-induced
      human osteosarcoma cell line, MG-63. A brown alga, Sargassum hemipyllum promoted
      most its activity, showing more than 11-fold. When we attempted to partially
      purify the active substances by particular two-step chromatography, two peaks of
      active fractions were obtained. These fractioned materials exhibited the heat
      stable and non-cytotoxic characters with the molecular weight less than 3000.

PMID- 22358900
TI  - Preface.

PMID- 22358901
TI  - Improved methods for investigating the external redox potential in hybridoma cell
      culture.
AB  - Because of the interest in understanding and optimizing secretion of proteins
      from mammalian cells, reliable and more reproducible methods are needed to
      monitor the external redox potential of animal cells in suspension culture. An
      improved off-line method was established that greatly reduces the typically long
      response time of redox electrodes in cell culture media and improves the
      standardization of redox probes. In addition, the dependence of medium redox
      potential on dissolved oxygen concentrations and pH was investigated using cell
      free medium. Off-line as well as on-line redox potential measurements were then
      applied to spinner or bioreactor cultures of murine hybridoma cells. Serum
      containing or protein-free medium were used. The time dependence of the
      experimentally determined external redox potential was found to be affected not
      only by oxygen, pH, and medium composition. but to a significant extent by the
      rate of generation of reductants by hybridoma cells. The observed specific rate
      of medium reduction by generation of reductants (DeltamV h(-1) viable cell(-1))
      decreased during exponential growth while cell number increased from 2*10(5)
      viable cells ml(-1) to 3.5*10(6) viable cells ml(-1). This rate, however, was
      essentially constant at -7.3 mV h(-1)+/-3.7 mV h(-1) per 10(10) viable cells
      during growth under conditions of constant dissolved oxygen tension and constant
      pH. Using these observations, the quantity of reductants synthesized and secreted
      into the medium by viable hybridoma cells was estimated to be approximately 1.3
      mole h(-1) per 10(10) viable hybridoma cells. The time course of specific
      monoclonal antibody secretion rate did not correlate with changes in the external
      oxidation/reduction potential in either serum containing or protein-free medium.

PMID- 22358902
TI  - CHO cell growth and recombinant interferon-gamma production: Effects of BSA,
      Pluronic and lipids.
AB  - The role of bovine serum albumin in mammalian cell cultures and the possibility
      of its substitution by other components in a serum-free medium has been
      investigated. In this study, BSA was shown to be important for growth and product
      formation in CHO cells expressing recombinant human interferon-gamma. There were
      indications that its stimulating growth effect was dependent on the source of BSA
      used and probably was related to the purification procedure used for the
      production of the desired albumin fraction. Cell growth did not occur in the
      absence of BSA but at low concentration (1 mg ml(-1)) it was stimulated by the
      addition of a combination of a commercial lipid mixture plus Pluronic F68.
      However, under the latter conditions IFN-gamma production was adversely effected.
      The importance of individual lipid components was investigated using a
      statistical approach based on a Plackett-Burman design. Linoleic acid was
      identified as a positive variable for cell growth while cholesterol was
      identified as a negative variable for both cell growth and IFN-gamma production.
      When a combination of linoleic acid plus Pluronic F68 was included in the
      formulation of low BSA medium, cell growth was similar to that at high BSA
      concentration (5 mg ml(-1)) but the IFN-gamma concentration was significantly
      reduced (ca. 45%).

PMID- 22358903
TI  - Efficient membrane targeting of the chick nicotinic acetylcholine receptor alpha
      subunit in stable insect cell lines.
AB  - We have synthesised the alpha-subunit of the chick nicotinic acetylcholine
      receptor (nAChR) in stable, continuous insect (Spodoptera frugiperda) cell lines.
      A cDNA was integrated randomly into the insect cell genome under control of a
      baculovius immediate early gene promoter. Transformed cells were obtained by co
      transfection of the insect cells with pIEK1.nAChRalpha, encoding the alpha
      subunit cDNA, and pIEK1.neo, encoding the neomycin resistance gene. G-418
      resistant clones were selected and expanded into continuous cell lines
      synthesising the chick nAChR alpha-subunit. Using fluorescence microscopy and
      ligand binding studies we were able to demonstrate efficient membrane targeting
      of the receptor subunit in the insect cell plasma membrane. Stable insect cell
      lines may thus have significant advantages over transient baculovirus vectors for
      the synthesis and characterisation of heterologous receptor proteins.

PMID- 22358904
TI  - Complementation cell lines for viral vectors to be used in gene therapy.
AB  - Viral vectors provide a highly efficient method for the transfer of foreign genes
      into a variety of quiescent or dividing eukaryotic cells from many animal
      origins. While recombinant vectors derived from an increasing number of mammalian
      viruses (herpes simplex virus, autonomous and non-autonomous parvoviruses,
      poxviruses, retroviruses, adenoviruses available today, vectors based on murine
      retroviruses and human adenoviruses constitute preferential candidates for the
      delivery of marker or therapeutic genes into human somatic cells. The
      availability of such vectors has made possible the recent transition of human
      gene therapy from laboratory benches to clinical settings. Most current
      recombinant vectors have been generated by deleting essential viral genes in
      order to make space available for the introduction of passenger genes. Such
      vectors are therefore unable to replicate in the absence of these critical gene
      products and their production relies on the development of stable complementation
      cell lines providingin trans the missing viral functions. Although
      complementation (or packaging) cell lines are available for both adenovirus and
      retrovirus vectors, their respective drawbacks still limit their use to research
      applications and phase I clinical trials. The future success or failure of human
      gene therapy will therefore rely on the production of improved generations of
      packaging cell lines that can produce safer and more efficient vectors which are
      fully adapted to large scale production and clinical applications.

PMID- 22358905
TI  - Production of monoclonal antibodies and ELISA for thebaine and codeine.
AB  - The ratio of hapten and bovine serum albumin in antigen conjugate was exactly
      determined by matrix-assisted laser desorption/ionization mass spectrometry.
      Monoclonal antibodies against thebaine and codeine were produced by hybridoma
      fused with the sprenocytes immunized with thebaine- and codeine-bovine serum
      albumin conjugate and HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. No
      cross-reaction of anti-thebaine antibody against morphine was observed. Very
      small cross-reaction appeared in codeine (0.004%). The cross-reaction of anti
      codeine antibody against morphine and thebaine was 2.97 and 5.98%, respectively.
      The full measuring range of the assay extends from 60 pg mL to 1 ng mL for
      thebaine and 1 ng mL to 100 ng mL for codeine.

PMID- 22358906
TI  - Separation of growth-stimulating activity of BSA fraction V from the bulk of
      albumin using Heparin Sepharose Chromatography.
AB  - Bovine serum albumin (BSA) is a potential source of biological contamination in
      cell culture medium. The aim of this work was to attempt to replace BSA in low
      serum and serum-free medium (SFM). BSA fraction V was subjected to a variety of
      processes in order to determine if the growth promoting activity observed for NRK
      cells could be extracted from the BSA molecule. These included solvent
      extractions, diafiltration, reverse phase HPLC and affinity chromatography using
      heparin sepharose. Solvent extraction and diafiltration failed to remove the
      activity from the BSA. Affinity chromatography using heparin sepharose indicated
      that all of the activity observed with BSA was retained in the 0.5 M NaCl
      fraction and was associated with less than 3% of the original protein. The major
      protein band in the 0.5 M NaCl fraction had the same apparent molecular weight as
      albumin (as seen by SDS-PAGE and analytical reverse phase HPLC). Unlike the
      untreated BSA, the 0.5 M NaCl fraction was partially susceptible to proteolytic
      digestion and to variations in pH.

PMID- 22358907
TI  - The economic production of anti-microbial factor from human promyelocytes in low
      serum containing medium under chemostat cultivation.
AB  - It proves that a purifed Anti-Microbial Factor (AMF) from human promyelocytes has
      strong activity on Gram(-) and Gram(+) bacteria, showing 0.5 (MUg/ml) of Minimal
      Bacterical Concentration (MBC) on bothE. coli andS. aureus. For mass production
      of AMF, chemostat cultivation is recommended to accumulate cells out of the
      reactor since it is an intracellular protein and its system requires only 1%
      serum in the medium. Its production process proves to be closely growth-related.
      1.7*10(-8) (MUg/viable cell/day) of maximum specific AMF production rate is
      estimated at 0.026 h(-1) of dilution rate, maintaining 6*10(6) (viable cell/ml).
      Ca. 300 (mg/ml) of crude AMF can be obtained for 50 days of continuous
      cultivation under optimal conditions. The cell growth reaches relatively fast
      steady state.

PMID- 22358909
TI  - Introduction : Cell culture engineering V.

PMID- 22358908
TI  - Transfection of rabbit articular chondrocytes by the calcium phosphate procedure:
      Improvement of efficiency and reproducibility.
AB  - The understanding of cartilage disorders relies on the possibility of studying
      mechanisms which monitor the regulation of matrix protein genes through
      introducing efficiently and in a reproducible manner these genes, or their
      regulatory regions, into cells. To this end, we attempted to improve the
      transfection efficiency of rabbit articular chondrocytes by the calcium phosphate
      procedure. Transfection efficiencies were assessed by measuring the expression of
      the Lac Z reporter gene encoding beta-galactosidase using anin situ staining (X
      gal staining) and an enzymatic assay (beta-galactosidase assay).Results revealed
      that addition of 4 U ml(-1) of hyaluronidase before and during transfection
      increases by 2 to 4-fold the transfection efficiency of rabbit articular
      chondrocytes. Furthermore, we demonstrated that the use of a "giant" calcium
      phosphate DNA coprecipitate gives a higher transfection efficiency and much more
      reproducible results than those obtained with classical small volumes of
      precipitates.

PMID- 22358910
TI  - Engineering challenges in high density cell culture systems.
AB  - High density cell culture systems offer the advantage of production of bio
      pharmaceuticals in compact bioreactors with high volumetric production rates;
      however, these systems are difficult to design and operate. First of all, the
      cells have to be retained in the bioreactor by physical means during perfusion.
      The design of the cell retention is the key to performance of high density cell
      culture systems. Oxygenation and media design are also important for maximizing
      the cell number. In high density perfusion reactors, variable cell density, and
      hence the metabolic demand, require constant adjustment of perfusion rates. The
      use of cell specific perfusion rate (CSPR) control provides a constant
      environment to the cells resulting in consistent production. On-line measurement
      of cell density and metabolic activities can be used for the estimation of cell
      densities and the control of CSPR. Issues related to mass transfer and mixing
      become more important at high cell densities. Due to the difference in mass
      transfer coefficients for oxygen and CO(2), a significant accumulation of
      dissolved CO(2) is experienced with silicone tubing aeration. Also, mixing is
      observed to decrease at high densities. Base addition, if not properly done,
      could result in localized cell lysis and poor culture performance. Non-uniform
      mixing in reactors promotes the heterogeneity of the culture. Cell aggregation
      results in segregation of the cells within different mixing zones. This paper
      discusses these issues and makes recommendations for further development of high
      density cell culture bioreactors.

PMID- 22358911
TI  - Analysis of recombinat glycoproteins by mass spectrometry.
AB  - The advent of new technologies for analysis of biopolymers by mass spectrometry
      has revolutionised strategies for recombinant protein characterization. The
      principal recent developments have been matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry. Using these
      tools, accurate molecular mass determinations can now be obtained routinely-often
      using minute (picomole-femtomole) quantities of protein or protein fragments.
      These techniques have proved indispensible for detailed characterization of the
      post-translational modifications of recombinant proteins produced by eukaryotic
      systems. Glycosylation is arguably the most important and complex of these
      modifications and has prompted widespread use of these new techniques. In this
      mini-review article I describe recent advances in the use of mass spectrometry
      for analysis of recombinant glycoproteins.

PMID- 22358912
TI  - Development of a serum-free medium using computer-assisted factorial design and
      analysis.
AB  - Stepwise screening of media supplements using factorial design and analysis was
      employed in the development of serum-free medium for a recombinant Chinese
      hamster ovary cell line. The effects (growth and target protein production) of
      different combinations were measured at two time points to ensure adequate
      response. The results were analysed by a computer program specialized in
      factorial analysis. The formulation deduced from the previous experiment was used
      as the new basal medium for the next screening. Certain significant nutrients
      were studied again in a more 'advanced' formulation in order to analyse the
      potential synergistic effects with new media components. Compared to cells grown
      in serum-containing medium, cells adapted to the final formulation of the serum
      free medium had a comparable growth rate but a four fold increase in the active
      protein production.

PMID- 22358913
TI  - Effect of endogenous methylglyoxal on Chinese hamster ovary cells grown in
      culture.
AB  - Methylglyoxal is a ketoaldehyde that reacts readily under physiological
      conditions with biologically relevant ligands, such as amine and sulfhydryl
      groups. It is produced in mammalian cells primarily as a by-product of
      glycolysis. The level of glucose, L-glutamine and fetal bovine serum in culture
      media was found to significantly affect levels of intracellular methylglyoxal in
      Chinese hamster ovary cells. Medium with 25 mM glucose and 5 mM L-glutamine
      caused an increase in free methylglyoxal levels of 90 to 100% relative to medium
      containing 5 mM glucose and 2 mM L-glutamine. Both of these media compositions
      are representative of those found in commercially available media. Pseudomonas
      putida glyoxalase I was expressed in Chinese hamster ovary cells to enhance
      methylglyoxal detoxification. The Chinese hamster ovary cell clones showed an 80
      to 90% decrease in free methylglyoxal levels. The colony-forming ability of these
      cells was compared to wild-type Chinese hamster ovary cells under conditions
      found to cause elevated methylglyoxal levels. The wild-type cells showed a 10%
      decrease in colony-forming ability relative to the clones. This decrease was
      found to be statistically significant (P>0.99) by analysis of variance. The
      variation in colony-forming ability amongst the clones was statistically
      insignificant. More importantly, the clones shoed increased colony-forming
      ability relative to the wild-type cells under conditions of higher methylglyoxal
      production with fair to good statistical significance (P>0.75 to P>0.95). This
      result is the first quantifiable evidence that endogenously produced
      methylglyoxal can negatively affect cell function under conditions found in
      animal cell culture.

PMID- 22358914
TI  - Degradative activities in a recombinant chinese hamster ovary cell culture.
AB  - Two degradative activities were found in a recombinant Chinese hamster ovary cell
      culture. These activities became more dominant under high cell density and
      extended running time, as achieved in a semi-continous perfusion culture. The
      first, insulin degradative activity caused a growth upset in the 3rd cycle of the
      perfusion culture and shortened the length of the bioreactor process. The second
      activity, derived from the neutral pH stable sialidase, was found to affect the
      integrity of the carbohydrate structure of the recombinant protein, causing
      increase in heterogeneity in molecular weight and pI of the glycoforms. The most
      efficient way to overcome these problems may be the use of genetically altered
      'designer cells' as the production cell line.

PMID- 22358915
TI  - Dissolved carbon dioxide accumulation in a large scale and high density
      production of TGFbeta receptor with baculovirus infected Sf-9 cells.
AB  - Production of a TGFbeta receptor with high density baculovirus infected Sf-9
      cells (7*10(6)cells ml(-1)) served as a test run for a retrofitted 150 L
      microbial fermentor. The entire 110 L batch run was performed in serum free
      medium, with an addition of a concentrated amino acid and yeastolate mixture at
      the time of infection. This addition strategy has been proven effective at a
      small scale by enabling cultures to maintain maximum product yield. In the
      bioreactor however, while cellular growth was comparable to that of the smaller
      scale control, TGFbeta receptor production was three fold below the control. To
      minimize the mechanical stress, low flow rate of pure oxygen was used to control
      the dissolved oxygen at 40%. As a consequence, it seems that this aeration
      strategy involved an accumulation of dissolved carbon dioxide that in turn
      inhibited the protein production. A model has been developed that estimated the
      CO(2) partial pressure in the culture to be in the vicinity of 0.15 atm. The
      effect of dissolved CO(2) at this concentration has been assessed at smaller
      scale for TGFbeta receptor and beta-gal expression, in controlled atmosphere
      incubators.

PMID- 22358916
TI  - CO(2) in large-scale and high-density CHO cell perfusion culture.
AB  - Productivity in a CHO perfusion culture reactor was maximized when pCO(2) was
      maintained in the range of 30-76 mm Hg. Higher levels of pCO(2) (> 150 mm Hg)
      resulted in CHO cell growth inhibition and dramatic reduction in productivity. We
      measured the oxygen utilization and CO(2) production rates for CHO cells in
      perfusion culture at 5.55*10(-17) mol cell(-1) sec(-1) and 5.36*10(-17) mol cell(
      1) sec(-1) respectively. A simple method to directly measure the mass transfer
      coefficients for oxygen and carbon dioxide was also developed. For a 500 L
      bioreactor using pure oxygen sparge at 0.002 VVM from a microporous frit sparger,
      the overall apparent transfer rates (k(L)a+k(A)A) for oxygen and carbon dioxide
      were 0.07264 min(-1) and 0.002962 min(-1) respectively. Thus, while a very low
      flow rate of pure oxygen microbubbles would be adequate to meet oxygen supply
      requirements for up to 2.1*10(7) cells/mL, the low CO(2) removal efficiency would
      limit culture density to only 2.4*10(6) cells/mL. An additional model was
      developed to predict the effect of bubble size on oxygen and CO(2) transfer
      rates. If pure oxygen is used in both the headspace and sparge, then the sparging
      rate can be minimized by the use of bubbles in the size range of 2-3 mm. For
      bubbles in this size range, the ratio of oxygen supply to carbon dioxide removal
      rates is matched to the ratio of metabolic oxygen utilization and carbon dioxide
      generation rates. Using this strategy in the 500 L reactor, we predict that
      dissolved oxygen and CO(2) levels can be maintained in the range to support
      maximum productivity (40% DO, 76 mm Hg pCO(2)) for a culture at 10(7) cells/mL,
      and with a minimum sparge rate of 0.006 vessel volumes per minute.A = volumetric
      agitated gas-liquid interfacial area at the top of the liquid, 1/mB = cell broth
      bleeding rate from the vessel, L/minCER = carbon dioxide evolution rate in the
      bioreactor, mol/min[CO(2)] = dissolved CO(2) concentration in liquid, M[CO(2)](*)
      = CO(2) concentration in equilibrium with sparger gas, M[CO(2)](**) = CO(2)
      concentration in equilibrium with headspace gas, MCO(2)(1) = dissolved carbon
      dioxide molecule in water[C(T)] = total carbonic species concentration in
      bioreactor medium, M[C(T)](F) = total carbonic species concentration in feed
      medium, MD = bioreactor diameter, mD(I) = impeller diameter, mD(b) = the initial
      delivered bubble diameter, mF = fresh medium feeding rate, L/minH(L) = liquid
      height in the vessel, mk(A) = carbon dioxide transfer coefficient at liquid
      surface, m/mink (infA) (supO) = oxygen transfer coefficient at liquid surface,
      m/min.

PMID- 22358917
TI  - Assessment of virus infection in cultured cells using metabolic monitoring.
AB  - A rapid, in-process assessment of virus replication is disired to quickly
      investigate the effects of process parameters on virus infection, and to monitor
      consistency of process in routine manufacturing of viral vaccines. Live virus
      potency assays are generally based on plaque formation, cytopathic effect, or
      antigen production (TCID(50)) and can take days to weeks to complete.
      Interestingly, when infected with viruses, cultured cells undergo changes in
      cellular metabolism that can be easily measured. These phenomena appear to be
      common as they has been observed in a variety of virus-host systems, e.g., in
      insect cells infected with baculovirus, Vero cells infected with Rotavirus, MRC-5
      cells infected with Hepatitis A virus, and MRC-5 cells infected with the
      Varicella Zoster Virus (VZV). In this article, changes in glycolytic metabolism
      of MRC-5 cells as a result of CVZ infection are described. Both glucose
      consumption and lactate production in VZV infected MRC-5 cells are significantly
      elevated in comparison to uninfected cells. Based on this result, a rapid, in
      process assay to follow VZV infection has been developed. The relative increase
      in lactate production in infected cells (alpha) increases as the infection
      progresses and then plateaus as the infection peaks. This plateau correlates with
      time of peak virus titer and could be used as a harvest triggering parameter in a
      virus production process.X(u) = cell density of uninfected cellsX(i) = cell
      density of infected cellsX(T) = total cell densityL(i) = cumulative lactate
      production in infected culturesL(u) = cumulative lactate production in uninfected
      culturesq(Li) = specific lactate production of infected cellsq(Lu) = specific
      lactate production of uninfected cellsk(1), K(2) = constants.

PMID- 22358918
TI  - Homogenisation and oxygen transfer rates in large agitated and sparged animal
      cell bioreactors: Some implications for growth and production.
AB  - Because of concern for cell damage, very low agitation energy inputs have been
      used in industrial animal cell bioreactors, typical values being two orders of
      magnitude less than those found in bacterial fermentations. Aeration rates are
      also very small. As a result, such bioreactors might be both poorly mixed and
      also unable to provide the higher oxygen up-take rates demanded by more intensive
      operation. This paper reports experimental studies both of K( L ) a and of mixing
      (via pH measurements) in bioreactors up to 8 m(3) at Wellcome and of scaled down
      models of such reactors at Birmingham. Alongside these physical measurements,
      sensitivity of certain cell lines to continuously controlled dO(2) has been
      studied and the oxygen up-take rates measured in representative growth
      conditions. An analysis of characteristic times and mixing theory, together with
      other recent work showing that more vigorous agitation and aeration can be used
      especially in the presence of Pluronic F-68, indicates ways of improving their
      performance. pH gradients offer a special challenge.

PMID- 22358919
TI  - Characterization of agitation environments in 250 ml spinner vessel, 3 L, and 20
      L reactor vessels used for animal cell microcarrier culture.
AB  - Three dimensional particle tracking velocimetry (3-D PTV) was used to
      characterize the flow fields in the impeller region of three microcarrier reactor
      vessels. Three typical cell culture bioreactors were chosen: 250 ml small-scale
      spinner vessels, 3 L bench-scale reactor, and 20 L medium-scale reactor.
      Conditions studied correspond to the actual operating conditions in industrial
      setting and were determined based on the current scale-up paradigm: the
      Kolmogorov eddy length criterion. In this paper we present characterization of
      hydrodynamics on the basis of flow structures produced because of agitation. Flow
      structures were determined from 3-D mean velocity results obtained using 3-D PTV.
      Although the impellers used in 3 L and 20 L reactors were almost identical, the
      flow structures produced in the two reactors differed considerably. Results
      indicate that near geometric scale up does not necessarily amount to scale-up of
      flow patterns and indicates that intensity as well as distribution of energy may
      vary considerably during such a scale-up.

PMID- 22358920
TI  - Insights into protective effects of medium additives on animal cells under fluid
      stresses: the hydrophobic interactions.
AB  - Animal cells in suspension culture can suffer severe mechanical damage from
      bursting gas bubbles or other hydrodynamic force sources. Certain chemical
      additives in the culture media, particularly some surface-active chemicals, can
      effectively protect animal cells against such damage. Previously we proposed that
      the protective effect is associated with the adsorption of the additives in the
      cell membrane through hydrophobic binding of the surface-active molecules to the
      membrane. Adsorption of the additives to the cell membrane may lead to decreased
      hydrophobicity of the cell surface, thus eliminating cell adhesion to bubbles and
      reducing cell damage from bursting bubbles. In this study, we measured the
      hydrophobicity of two insect cell lines based on cell adhesion to hydrocarbon
      phase and its influence by surface-active chemicals, Pluronic F68, a
      methylcellulose and a polyethylene glycol. The experimental results showed strong
      support for the aforecited cell protection mechanism.

PMID- 22358921
TI  - Human diploid fibroblast growth on polystyrene microcarriers in aggregates.
AB  - Polystyrene microcarriers were prepared in four size ranges (53-63 MUm, 90-125
      MUm, 150-180 MUm and 300-355 MUm) and examined for ability to support attachment
      and growth of human diploid fibroblasts. Cells attached rapidly to the
      microcarriers and there was a direct relationship between cell attachment and
      microcarrier aggregation. Phasecontrast and scanning electron microscopic studies
      revealed that while aggregation was extensive, most of the aggregate consisted of
      void volume. Cell growth studies demonstrated that human diploid fibroblasts
      proliferated well in microcarrier aggregates, reaching densities of 2.5-3*10(6)
      cells per 2 ml dish after 6 days from an inoculum of 0.5*10(6) cells per dish.
      When cells were added to the microcarriers at higher density (up to 5*10(6) cells
      per 2-ml culture), there was little net growth but the cells remained viable over
      a 7-day period. In contrast, cells died when plated under the same conditions in
      monolayer culture. When the microcarriers were used in suspension culture, rapid
      cell attachment and rapid microcarrier aggregation also occurred. In 100-ml
      suspension culture, a cell density of 0.7*10(6) cells per ml was reached after 7
      days from an inoculum of 0.1*10(6) cells. Based on these data, we conclude that
      microcarrier aggregation is not detrimental to fibroblast growth. These data also
      indicate that small microcarriers (53-63 MUm) (previously thought to be too small
      to support the growth of diploid fibroblasts) can support fibroblast growth and
      this occurs primarily because microcarriers in this size range efficiently form
      aggregates with the cells.

PMID- 22358922
TI  - Lysis-free separation of hybridoma cells by continuous disc stack centrifugation.
AB  - The non-destructive removal of hybridoma cells from fermentation broth with an
      improved disc stack centrifuge (CSA1, Westfalia Separator AG, Oelde, Germany) was
      investigated. The centrifuge was equipped with a hydrohermetic feed system, which
      allowed a gentle, shearless acceleration of the cells inside the bowl. No
      significant cell damage was observed during the separation of hybridoma cells
      from repeated batch fermentation in 100 liter scale. In the clarified liquid
      phase there was no increase in Lactate-Dehydrogenase (LDH) activity.
      Consequently, there was no increased exposure of the product to intracellular
      components.Due to continuous operation with a periodic and automatic discharge of
      sediment, a high throughput was achieved without any considerable loss of
      product. The clarification for mammalian cells was in the range of 99% to 99.9%,
      depending on the operating conditions. The content of cell debris and other small
      particles decreased about 30 to 50%, depending on the particle load in the feed
      stream. The centrifuge was fully contained; cleaning and sterilizing in place
      possible. Therefore, the decice could be integrated easily into the fermentation
      process.

PMID- 22358923
TI  - Comparison of the production of a human monoclonal antibody against HIV-1 by
      heterohybridoma cells and recombinant CHO cells: A flow cytometric study.
AB  - The production of human monoclonal antibodies for therapeutic use is of
      increasing importance for treatment of viral infections such as AIDS. As human x
      mouse heterohybridomas rarely reach the growth rates and cell specific production
      rates of mouse hybridomas the transfection of standard cell lines, such as CHO or
      BHK, is a promising alternative. This has the additional advantage that the IgG
      subtype can be changed to suit the desired application. However, the use of a
      cell line that has not originally developed to produce antibodies, as lymphocytes
      and myeloma cells have, might have unrecognised drawbacks. This will be
      especially significant in the case of antibodies as each molecule consists of 4
      chains linked by disulphide bonds which require specific intracellular factors to
      be properly folded and processed (Heavy chain binding protein, Protein Disulfide
      Isomerase a.o.). In this study we have therefore compared two cell lines: a human
      x mouse heterohybridoma producing IAM-2F5, a human IgG(3) antibody specific for
      HIV-1 with neutralising properties and a Chinese Hamster Ovary cell transfected
      with dihydrofolate reductase and with the heavy and light chain genes of IAM-2F5
      modified to IgG(1). From each cell line three subclones were selected with low,
      medium and high specific production rates. Batch cultures were performed and the
      following cellular parameters analysed by flow cytometry; 1) total RNA content
      (translational activity); 2) total protein content; 3) cell cycle phase
      distribution; 4) concentration of light and heavy chains; 5) concentration of
      helper proteins such as BiP and PDI. The production rate of heterohybridoma cells
      was best reflected in the intracellular concentration of kappa chain, while the
      gamma chain concentration was comparable for all three subclones. In the CHO
      cells the gamma chain expression and thus gene copy number appeared to be the
      limiting factor. The GRP78/BiP concentration in CHO remained unchanged in spite
      of a 5-fold higher concentration of gamma chain in the high producing subclone.
      The PDI concentration in CHO cells was much lower compared to the heterohybridoma
      cells, irrespective of production rates.

PMID- 22358924
TI  - Super-CHO-A cell line capable of autocrine growth under fully defined protein
      free conditions.
AB  - Chinese Hamster Ovary (CHO) cells are widely used for the large scale production
      of recombinant biopharmaceuticals. Growth of the CHO-K1 cell line has been
      demonstrated in serum-free medium containing insulin, transferrin and selenium.
      In an attempt to get autocrine growth in protein-free medium, DNA coding for
      insulin and transferrin production was transfected into CHO-K1 cells. Transferrin
      was expressed well, with clones secreting approximately 1000 ng/10(6) cells/24h.
      Insulin was poorly expressed, with rates peaking at 5 ng/10(6) cells/24h.
      Characterisation of the secreted insulin indicated that the CHO cells were
      incompletely processing the insulin molecule. Site-directed mutagenesis was used
      to introduce a furin (prohormone converting enzyme) recognition sequence into the
      insulin molecule, allowing the production of active insulin. However, the levels
      were still too low to support autocrine growth. Further investigations revealed
      insulin degrading activity (presumably due to the presence of insulin degrading
      enzymes) in the cytoplasm of CHO cells. To overcome these problems insulin-like
      growth factor I (instead of insulin) was transfected into the cells. IGF-1 was
      completely processed and expressed at rates greater than 500 ng/10(6)cells/24h.
      In this paper we report autonomous growth of the transfected CHO-K1 cell line
      expressing transferrin and IGF-1 in protein-free medium without the addition of
      exogenous growth factors. Growth rates and final cell densities of these cells
      were identical to that of the parent cell line CHO-K1 growing in insulin,
      transferrin, and selenium supplemented serum-free media.

PMID- 22358925
TI  - Regulation of cell growth by IRF-1 in BHK-21 cells.
AB  - Most cell lines that are used for the production of recombinant proteins
      proliferate spontaneously at a high rate. In many types of cultivation systems
      these cells still keep growing after having reached the desired cell density.
      Further proliferation in batch cultures leads to cell death as a consequence of
      nutrient and oxygen depletion as well as to accumulation of lactate and toxic
      products. Consequently, in many technical processes, the surplus of cells is
      removed.We have established cell lines in which proliferation is controlled by a
      physiological regulator, IRF-1. IRF-1 (Interferon Regulatory Factor 1) is a
      transcriptional activator and acts as a tumor suppressor. Constitutive
      overexpression of recombinant IRF-1 leads to inhibition of cell growth. The
      extent of this growth arrest depends on the intracellular concentration of active
      IRF-1. To allow IRF-1 expression in various mammalian cells a system for
      conditional IRF-1 activation has been established. A fusion protein composed of
      IRF-1 and the hormone binding domain of the human estrogen receptor, was used.
      This system allows to control gradually the growth of several mammalian cell
      lines by adjusting the intracellular concentration of active IRF-1 via estradiol
      in the medium. We have evaluated BHK-21 cells with respect to IRF-1 mediated cell
      growth inhibition and expression of two secreted proteins. Whereas the
      productivity of proliferation inhibited cells with respect to constitutively
      transcribed IgG genes is reduced, productivity of another secreted protein which
      is controlled by an IRF-1 inducible promoter is strongly enhanced under these
      conditions.

PMID- 22358926
TI  - Controllable genetic manipulation of apoptosis of cells in culture.
AB  - Apoptosis of mammalian cell is under the control of a wide range of intracellular
      and extracellular factors-amongst them proteases, protein kinases, cytokines and
      the protein products of oncogenes and tumour suppressor genes. The c-myc proto
      oncogene encodes an essential component of the cell's proliferative machinery and
      its deregulated expression is implicated in many cancers. Under certain
      conditions, c-Myc also acts as a potent inducer of apoptosis. We have developed a
      'switchable' chimaeric c-Myc protein whose activity is dependent on the synthetic
      ligand, 4-hydroxytamoxifen. In cells expressing this switchable c-Myc,
      proliferation and apoptosis in cultured fibroblasts can be regulated by addition
      of 4-hydroxytamoxifen. We have further demonstrated the utility of a switchable
      gene transcription system for the induction of proteins with pro-apoptotic
      effect. Myc-induced apoptosis is inhibited by the action of certain cytokines or
      by expresson of exogenous proteins with anti-apoptotic potential such as Bcl-2.
      We show that inhibition of p53 using dominant negative molecules inhibits
      apoptosis induced by DNA damage but has little effect on Myc-induced apoptosis.
      Finally, we have also been able to modulate a relatively late stage in apoptosis
      using inhibitors of cysteine proteases. Our data suggest a model in which the
      integrated activities of several proteins with diverse molecular functions may
      determine whether a particular cell undergoes apoptosis but that, once the actual
      catalytic machinery is engaged, the apoptotic process is irreversible.

PMID- 22358927
TI  - Bcl-2 inhibits apoptosis and extends recombinant protein production in cells
      infected with Sindbis viral vectors.
AB  - Viruses carrying foreign genes are often used for the production of recombinant
      proteins in mammalian cells and other eukaryotic expression systems. Though high
      levels of gene expression are possible using viral vectors, the host cell
      generally responds to the infection by inducing apoptotic cell death within
      several days, abruptly ending protein production. It has recently been
      demonstrated, however, that apoptosis can be suppressed in virally infected cells
      using anti-apoptotic genes, such as bcl-2. In this study, stably transfected rat
      carcinomal cell lines, AT3-bcl2 and AT3-neo, were infected with a Sindbis virus
      carrying the gene for chloramphenicol acetyltransferase (CAT) in an effort to
      determine the effect of bcl-2 on cell viability and recombinant protein
      production. Infected AT3-bcl2 cells consistently maintained viabilities close to
      100% and a growth rate equivalent to that of uninfected cells (0.040 h(-1)). In
      contrast, the Sindbis viral vector induced apoptosis in the AT3-neo cells, which
      were all dead by three days post-infection. Though infected AT3-neo cells
      generated higher levels of heterologous protein, over 1000 mUnits per well, CAT
      activity fell to zero by two days post-infection. In contrast, chloramphenicol
      acetyltransferase was present in AT3-bcl2 cells for almost a week, reaching a
      maximum level of 580 mUnits per well. In addition, recombinant protein production
      in AT3-bcl2 cells was extended and amplified by the regular addition of virus to
      the culture medium, a process which resulted in expression for the duration of
      the cell culture process.

PMID- 22358928
TI  - Foreign protein expression from S phase specific promoters in continuous cultures
      of recombinant CHO cells.
AB  - Foreign protein expression from the commonly used SV40 promoter has been found to
      be primarily during the S-phase of the cell cycle. Simple mathematical models
      with this cell cycle phase dependent expression of foreign protein suggest that
      the specific production rate will be proportional to the cell growth rate, which
      is particularly disadvantageous in high cell density fed-batch or perfusion
      bioreactors. In this study we investigate this predicted relationship between the
      production rate and growth rate by culturing recombinant CHO cells in a
      continuous suspension bioreactor. One CHO cell line, GS-26, has been stably
      transfected with the plasmid pSVgal, which contains the E. coli lac Z gene under
      the control of the SV40 promoter. This GS-26 cell line was grown in suspension
      cultures over a range of specific growth rates in batch and continuous modes. The
      intracellular beta-galactosidase activity was assayed using a standard
      spectrophotometric method after breaking the cells open and releasing the enzyme.
      A strong growth associated relationship is found between the intracellular beta
      galactosidase content and the specific growth rate in batch and continuous
      cultures, as predicted.

PMID- 22358929
TI  - Kinetics of retroviral production from the amphotropic PsiCRIP murine producer
      cell line.
AB  - Rapidly expanding development and practice of gene therapy requires the
      availability of large quantities of high titer retroviral supernatants. One way
      to achieve high retroviral titers is through improved understanding of the
      kinetics of retroviral production and decay, and the subsequent development of
      improved cell culture methods. In the present study we investigated the effects
      of different operational modes on the retroviral production of the NIH 3T3
      fibroblast derived amphotropic murine retroviral producing cell line
      pMFG/PsiCRIP. Semi-continuous culture (exchange of 50% of medium volume daily)
      was found to promote cell growth and enhance retroviral production. The rapid
      medium exchange resulted in significantly larger amounts of high titer
      supernatants and an extended production phase as compared to the batch control
      cultures. The specific viral productivity of the pMFG/PsiCRIP cells was in the
      range of 10 to 40 infectious viruses produced per thousand producer cells per
      day. The CV-1 African Green Monkey kidney cell line was used as the infection
      target. Lowering the serum level form 20% to 10% improved retroviral production
      slightly. However, at lower serum levels (1%, 5% and 10% (v/v)) growth of the
      producer cell line, and thus retroviral production, was directly proportional to
      the serum level. The half-life of the virus at 37 degrees C was found to be 5.5
      hours. Promoting the growth of producer cell lines can improve retroviral vectors
      titers and viral production. High cell density systems that allow for rapid cell
      growth and waste product removal are likely to be used to generate high-titer
      retroviral supernatants.

PMID- 22358930
TI  - Genetic engineering of alpha2,6-sialyltransferase in recombinant CHO cells and
      its effects on the sialylation of recombinant interferon-gamma.
AB  - The CHO cell line has achieved considerable commercial importance as a vehicle
      for the production of human therapeutic proteins, but is known to lack a
      functional copy of the gene coding for alpha2,6-sialyltransferase (EC 2.4.99.1).
      The cDNA for rat alpha2,6-ST was expressed in a recombinant CHO cell line making
      interferon-gamma, using a novel in vitro amplification vector. The enzyme was
      expressed efficiently, and resulted in up to 60% of the total sialic acids on
      interferon-gamma being linked in the alpha2,6-conformation. This sialic acid
      linkage distribution was more akin to that seen in natural human glycoproteins.
      In the most successful cell clones, expression of alpha2,6-sialyltransferase
      improved the overall level of sialylation by up to 56%, and had no adverse
      effects on cell growth, IFN-gamma productivity or other aspects of IFN-gamma
      glycosylation. These experiments demonstrate how the glycosylation machinery of
      rodent cells can be genetically manipulated to replicate human tissues.

PMID- 22358931
TI  - Effect of lipids on insect cell growth and expression of recombinant proteins in
      serum-free medium.
AB  - The lipid emulsion components of a serum-free insect cell medium were varied and
      evaluated for effects on cell growth and recombinant protein expression. The
      growth of High-Five(TM) cells was significantly affected by polyol Pluronic F-68
      and Tween-80, but not by lipids. Pluronic was essential for cell growth, while
      Tween-80 was required to achieve maximum cell densities. A dose response effect
      was observed for Tween-80 with optimal cell growth at a concentration of 25 mg/l.
      Cholesterol had a minor effect on cell growth, but was essential for the
      expression of recombinant proteins. The expression of beta-galactosidase (beta
      gal) was directly affected by cholesterol with optimal expression at a
      concentration of 5.4 mg/l. Vitamin E, important as an antioxidant to stabilize
      lipids, did not directly affect recombinant protein expression. Although lipids
      were not required for cell growth, the presence of lipids were required during
      the cell growth phase in order to achieve efficient infection with baculovirus.
      These studies help to define the important components, and range of
      concentrations, for lipid emulsions which can effectively replace serum in insect
      cell culture.

PMID- 22358932
TI  - In vitro production studies with a wild-type Helicoverpa baculovirus.
AB  - The potential use of a wild-type Helicoverpa baculovirus as a biopesticide, using
      insect cell culture for its production, has been investigated. A Helicoverpa zea
      cell line was adapted to grow in suspension culture using a serum-free medium,
      SF900II and serum supplemented SF900II. The serum supplemented cells were
      infected with a wild-type nuclear polyhedrosis virus of Helicoverpa armigera
      (HaNPV), at different stages of growth, in conditioned and tresh medium, to
      determine the effect of cell density on polyhedra production. Cultures infected
      at low cell densities, produced similar yields of virus (20-40 PIB/cell),
      irrespective of medium conditions. However, in infections which occurred at high
      cell densities, there was a 16-fold improvement in cell specific yields, when the
      spent medium was renewed with fresh medium prior to infection. Results indicated
      that only 60-70% of the viable cells in a culture produced polyhedra as a result
      of infections.

PMID- 22358933
TI  - The effect of dissolved oxygen tension and the utility of oxygen uptake rate in
      insect cell culture.
AB  - Dissolved oxygen tension and oxygen uptake rate are critical parameters in animal
      cell culture. However, only scarce information of such variables is available for
      insect cell culture. In this work, the effect of dissolved oxygen tension (DOT)
      and the utility of on-line oxygen uptake rate (OUR) measurements in monitoring
      Spodoptera frugiperda (Sf9) cultures were determined. Sf9 cells were grown at
      constant dissolved oxygen tensions in the range of 0 to 30%. Sf9 metabolism was
      affected only at DOT below 10%, as no significant differences on specific growth
      rate, cell concentration, amino acid consumption/production nor carbohydrates
      consumption rates were found at DOT between 10 and 30%. The specific growth rate
      and specific oxygen uptake rate followed typical Monod kinetics with respect to
      DOT. The calculated MU(max) and [Formula: see text] max were 0.033 h(-1) and
      3.82*10(-10) mole cell(-1)h(-1), respectively, and the corresponding saturation
      constants were 1.91 and 1.57%, respectively. In all aerated cultures, lactate was
      consumed only after glucose and fructose had been exhausted. The yield of lactate
      increased with decreasing DOT. It is proposed, that an 'apparent' DOT in non
      instrumented cultures can be inferred from the lactate yield of bioreactors as a
      function of DOT. Such a concept, can be a useful and important tool for
      determining the average dissolved oxygen tension in non-instrumented cultures. It
      was shown that the dynamic behavior of OUR can be correlated with monosaccharide
      (fructose and glucose) depletion and viable cell concentration. Accordingly, OUR
      can have two important applications in insect cell culture: for on-line
      estimation of viable cells, and as a possible feed-back control variable in
      automatic strategies of nutrient addition.

PMID- 22358934
TI  - Large scale production of recombinant mouse and rat growth hormone by fed-batch
      GS-NSO cell cultures.
AB  - Investigations of biological effects of prolonged elevation of growth hormone in
      animals such as mice and rats require large amounts of mouse and rat growth
      hormone (GH) materials. As an alternative to scarce and expensive pituitary
      derived materials, both mouse and rat GH were expressed in NSO murine myeloma
      cells transfected with a vector containing the glutamine synthetase (GS) gene and
      two copies of mouse or rat GH cDNA. For optimal expression, the mouse GH vector
      also contained sequences for targeting integration by homologous recombination.
      Fed-batch culture processes for such clones were developed using a serum-free,
      glutamine-free medium and scaled up to 250 L production scale reactors.
      Concentrated solutions of proteins, amino acids and glucose were fed periodically
      to extend cell growth and culture lifetime, which led to an increase in the
      maximum viable cell concentration to 3.5*10(9) cells/L and an up to 10 fold
      increase in final mouse and rat rGH titers in comparison with batch cultures. For
      successful scale up, similar culture environmental conditions were maintained at
      different scales, and specific issues in large scale reactors such as balancing
      oxygen supply and carbon dioxide removal, were addressed. Very similar cell
      growth and protein productivity were obtained in the fed-batch cultures at
      different scales and in different production runs. The final mouse and rat rGH
      titers were approximately 580 and 240 mg/L, respectively. During fed-batch
      cultures, the cell growth stage transition was accompanied by a change in
      cellular metabolism. The specific glucose consumption rate decreased
      significantly after the transition from the growth to stationary stage, while
      lactate was produced in the exponential growth stage and became consumed in the
      stationary stage. This was roughly coincident with the beginning of ammonia and
      glutamate accumulation at the entry of cells into the stationary stage as the
      result of a reduced glutamine consumption and periodic nutrient additions.

PMID- 22358935
TI  - Ammonium ion transport-a cause of cell death.
AB  - Ammonium can be transported into the cell by ion pumps in the cytoplasmic
      membrane. Ammonia then diffuse out through the cell membrane. A futile cycle is
      created that results in cytoplasmic acidification and extracellular
      alkalinisation. Ammonium transport can be quantified by measuring the
      extracellular pH changes occurring in a cell suspension (in PBS) after addition
      of ammonium. By using this technique, in combination with specific inhibitors of
      various ion pumps, it was shown that ammonium ions are transported across the
      cytoplasmic membrane by the Na(+)K(+)2Cl(-)-cotransporter in both hybridoma and
      myeloma cells. Further, the Na(+)/H(+) exchanger, which regulates intracellular
      pH by pumping out protons, was shown to be active during ammonium exposure. The
      viability of hybridoma cells suspended in PBS and exposed to NH (inf4) (sup+) for
      only 90 min, was reduced by 11% (50% necrosis and 50% apoptosis). A control cell
      suspension did not loose viability during this time. Turning off the activity of
      the Na(+)/H(+) exchanger (by amiloride) during ammonium exposure decreased
      viability further, while inhibiting transport itself (by bumetanide) restored
      viability to the same level as for the control experiment with bumetanide alone.
      These results show that one effect of ammonia/ammonium on cell physiology is
      specifically related to the inward transport of ammonium ions by membrane bound
      ion pumps.

PMID- 22358936
TI  - Continuous, high capacity reconstitution of nutrient media from concentrated
      intermediates.
AB  - We designed an Integrated Media Preparation System (IMPS) for continuous, on-line
      preparation of cell culture media and delivery to intermediate storage vessels or
      directly to a bioreactor. Key components of the IMPS include: a high precision,
      continuous fluid mixing device; formulation-specific liquid medium concentrates;
      validated process controls and membrane filtration; and automated dispensing into
      large volume flexible plastic containers. The IMPS system is designed to produce
      sterile, single-strength liquid medium from common raw materials at a delivery
      rate of 1000-3000 liters per hour and will manufacture homogenous batches from
      several thousand liters to over 60,000 liters. Fortified nutrient media prepared
      from multi-component 50X concentrates have been demonstrated to accelerate
      bioreactor seed chains, increase product yield, and reduce the overall
      manufacturing cost of nutrient medium. A productivity matrix will analyze the
      fully-loaded costs and contrast alternative methods for media preparation against
      projected biological yield.

PMID- 22358938
TI  - Cell culture process monitoring and control-a key to process optimization.

PMID- 22358937
TI  - The growth and phenotypic expression of human osteoblasts.
AB  - The care of patients with a skeletal deficiency currently involves the use of
      bone graft or a non-biologic material such as a metal or polymer. There are
      alternate possibilities in development which involve the growth of bone cells
      (osteoblasts) on degradable polymer scaffolds. These tissue engineering
      strategies require production of the polymeric scaffold, cellular harvest
      followed by either ex vivo or in vivo growth of the cells on the scaffold, and
      exploration of the interaction between the cell and scaffold. Research into these
      strategies utilizes cells from a variety of species, but clinical applications
      will likely require human osteoblasts. This study explores the process whereby
      human osteoblasts are harvested under sterile conditions during joint replacement
      surgery from normally discarded cancellous bone, transported from the operating
      room to the lab, and grown in culture. This process is feasible, and the cells
      express their phenotype via the production of alkaline phosphatase and collagen
      in culture.

PMID- 22358939
TI  - [Vascular ultrasonography].
AB  - Vascular ultrasound plays an important role in the visual depiction of arteries,
      veins, and changes of tissue in lymphatic diseases. In the case of arteries, this
      ranges from endothelial dysfunction over measuring the increase of intima media
      thickness to the detection of stenoses, occlusion, or aneurysm. Ultrasound helps
      to differentiate in functional arterial diseases such as primary and secondary
      Raynaud's syndrome as well as arterial compression syndromes like entrapment
      syndrome of different arterial regions or the chronic exceptional compartment
      syndrome of the lower leg. Ultrasound plays a central role in the diagnosis of
      rare arterial diseases like large vessel vasculitis, arterial dissection, cystic
      adventitial degeneration, and the differentiation of vascular malformation
      especially in children, thus, permitting ultrasound-guided intervention and
      follow-up controls. In venous thrombosis, sonography is the primary imaging
      method, while follow-up controls help in the prediction of recurrent venous
      thrombosis. Ultrasound is a tool to determine the cause and severity of chronic
      venous insufficiency and allows different therapeutic procedures for the
      treatment of varicose veins to be visually monitored.

PMID- 22358940
TI  - Evaluation of the antiviral effect of new compounds by using cellular cultures.
AB  - Replication Kinetics of HIV was studied under single-growth cycle conditions in
      C8166 lymphoblastoid cells by back-titrating released and cell-associated
      infectious virus et each time point. Under these conditions HIV seemed to
      replicate faster than previously estimated. The amount cell-associated virus
      always exceeded that detectable in the medium. In these conditions the
      replication curve of HIV is completed at 24 h post infection. At lower
      multiplicity of infection, virus yield peaks at approximately 72 h post
      infection, and the virus released in the medium is negligible with respect to
      that which remains cell-associated. The method based on back-titration of virus
      in cryolysates of C8166 cells infected with HIV and treated with antiviral
      compounds has been used to evaluate HIV sensitivity to some agents. This method
      allows a precise and quick determination of the degree of activity of antiviral
      drugs.

PMID- 22358941
TI  - Microbial immunomodulators: mannoprotein constituents ofCandida albicans with
      immunomodulatory activity in lymphocyte cultures of normal, glioma-bearing and
      HIV-infected subjects.

PMID- 22358942
TI  - Synthetic immunomodulators.
AB  - CONCLUSIONS: An effective boosting of the host immunocompetence is possible
      through synthetic immunomodulators, keeping in mind that they are no panacea for
      all microbial diseases. No drug is effective on all phases or effector cells of
      the immune response and it is postulated that in a near future combined therapies
      will be attempted with antibiotics or anti-cancer agents.

PMID- 22358943
TI  - Notes on the use of in vitro systems to investigate the activity and the
      mechanism of action of antineoplastic agents.

PMID- 22358944
TI  - Individuation of subcellular targets of antitumor agents by ultrastructural
      methods.

PMID- 22358945
TI  - Liposome mediated delivery of retinoids and aromatic polyamidines: Effects on
      growth of tumor cell lines.
AB  - This paper describes the increase of antiproliferative activity toward tumor cell
      lines of liposome-delivered retinoids and aromatic polyamidines.

PMID- 22358946
TI  - Protection against acute paraquat toxicity by ambroxol.
AB  - One of the earliest biochemical effects induced by the herbicide paraquat (PQ) is
      damage to type II pneumocytes with consequent depletion of surfactant (Skillrud
      and Martin, 1984). We made a series of studies on the possible protective effect
      of drug ambroxol, which induces surfactant synthesis from alveolar type II cells
      (Post et al. 1983). The cell line A-549, exposedin vitro to PQ concentrations
      ranging from 0.5*10(-4) to 2*10(-3) M, showed a significant dose-dependent loss
      of viability. Ambroxol (10 mg/ml) pretreated cells were more resistant to PQ,
      their viability starting to decrease from a PQ concentration of 0.8*10(-3) M.
      Membrane microviscosity was measured on the same cells. Cells treated with PQ
      alone showed a reduction of membrane microviscosity which was significantly
      counteracted by ambroxol pretreatment. The curves for membrane microviscosity of
      PQ and ambroxol-plus-PQ-treated cells overlapped those for cell viability,
      indicating that the stimulation of surfactant synthesisin vitro may be a
      prerequisite for counteracting some of the precocious effects of PQ. Partial
      protection from PQ- induced mortality was also obtainedin vivo.

PMID- 22358947
TI  - Antiviral activity of cyclopentenone prostaglandins: Block of virus protein
      synthesis and induction of stress proteins in polarized monkey kidney cells.

PMID- 22358948
TI  - Effects of the association of adriamycin with the polar solvent N-methylformamide
      on human melanoma cultured cells.

PMID- 22358949
TI  - Use of monoclonal antibodies in solid tumors diagnosis-the endometrial carcinoma.

PMID- 22358950
TI  - Expression of anchorin CII mRNA by cultured chondrocytes.
AB  - The establishment of a cell culture system promoting chondrocyte differentiation
      has been utilized to better characterize phenotypic stages of chondrogenesis at
      the cellular level. Although the expression of the type II collagen gene has been
      studied during "in vitro" chondrocyte differentiation, little is known about the
      expression of the gene coding for its receptor: anchorin CII. The modulation of
      the anchorin mRNA steady state level in chick embryo chondrocytes at different
      developmental stages is described here.The anchorin mRNA level was low in
      dedifferentiated chondrocytes, progressively increased after the cell transfer
      into suspension (a condition promoting differentiation), reached its maximal
      value after 4 weeks and decreased after 5 weeks.Therefore anchorin CII mRNA
      reaches its maximum level in hypertrophic stage II chondrocytes.

PMID- 22358951
TI  - ?4 integrin expression onin vitro andin vivo metastatic variants of lewis lung
      carcinoma.
AB  - The expression of beta4, alpha6, and beta1 integrin subunits has been
      investigated on somein vitro andin vivo murine metastatic variants derived from
      Lewis lung carcinoma (3LL). By the use of monoclonal antibodies which recognizes
      different epitopes of alpha6, beta1, and beta4 subunits we demonstrate that
      alpha6 and beta1 subunits are expressed in all metastatic variants of 3LL
      irrespective of their metastatic potential, whereas beta4 subunit is expressed
      only in highly metastasizing cells of 3LL. Northern blots of different metastatic
      variants probed with beta1 and beta4 subunits demonstrate thata) significant
      amounts of beta1 mRNA were detected in all metastatic variants of 3LL;b) mRNA
      corresponding to the described entire coding sequence of beta4 subunit is
      expressed only on highly metastasizing cells of 3LL. We conclude that beta4
      subunit is specifically expressed in highly metastasizig cells of 3LL while is
      undetectable in lower metastasizing ones.

PMID- 22358952
TI  - Intracellular immunization: Expression of antibody domains in the cytoplasm and
      in the nucleus of mammalian cells.

PMID- 22358953
TI  - Alternative methods in toxicology tests: In vitro toxicity.
AB  - Toxicity testing is required for new chemicals being introduced onto the market.
      The use of animals in evaluating chemical safety is costly and time consuming.
      Furthermore, there is the ethical need to develope alternative methods to reduce
      the required number of animals. The newin vitro assays offer numerous advantages
      such as speed, reproducibility and control of test conditions, and increased
      sensitivity. Although the dermal irritation assays might be substituted by thein
      vitro tests in the near future (Duffy, 1989), much work is required to evaluate
      organ toxicity within vitro methods. We present data regarding the use of
      Balb/3T3 mice fibroblasts and primary rat hepatocytes as test systems forin vitro
      toxicity. The end-points we have analysed are total protein content, dye
      accumulation in lysosomes, reductase mytochondrial activity, intracellular
      content and leakage of enzymes into the medium.

PMID- 22358954
TI  - Methylation state of the human HLA-DRa gene in transgenic mice.
AB  - We describe the tissue-specific expression and the reconstitution of the
      canonical methylation state of the human HLA-DRa gene in transgenic mice.

PMID- 22358955
TI  - Cell metabolism measurements in culture via microelectronic biosensors.
AB  - Silicon-based H(+)-sensitive biosensors in proximity to a cell population detect
      variations in cell metabolism via local measurements of changes in pH. The
      feasibility of this approach is shown in the case of ISFET devices.

PMID- 22358956
TI  - Characterization of a subfamily of zinc finger genes expressed in human
      hematopoietic cell lines.
AB  - We isolated by low strigency screening of a human erythroleukemia cDNA library
      (K562) 45 indipendent clones hybridizing to a Kruppel-like (HF.10) zinc finger
      cDNA. The expression of 15 such cDNAs in human hematopoietic cell lines was
      investigated. Preliminary sequence analysis of the zinc finger motifs in these
      cDNAs indicate that they belong to a subclass of the Cys-Cys/His-His motif,
      showing the highest homology to the Wilm's tumor and EGR1, EGR2 cDNAs.

PMID- 22358957
TI  - Cellular internalisation of bacterial toxins.

PMID- 22358958
TI  - Cytopathological features of cell suffering and death: Role of plasma membrane
      and cytoskeleton.
AB  - Morphological and ultrastructural modifications related to the cell injury and
      leading to cell death have been investigated by using different compounds. Data
      obtained by treating various cultured cells with a quinone (menadione), a polar
      solvent (NMF) and a bacterial protein toxin (toxin B fromClostridium difficile)
      are here reported Differences seem to exist between such injuries, but changes in
      plasma membrane structure, called surface blebbing phenomenon, represent a common
      feature which can be in any case detected. Our results also allow to hypothesize
      an important role of cytoskeleton in such a process.

PMID- 22358959
TI  - Cell damage by oxygen free radicals.
AB  - The exposure of isolated and cultured cells to oxygen free radicals generated
      extracellularly or intracellularly during the metabolism of foreing compounds
      results in the development of damage that eventually lead to cell death. Multiple
      mechanisms are involved in these cytopathological processes, including direct
      attack of free radicals to macromolecules essential for cell life, as well as
      indirect activation of catabolic processes such as proteases, endonucleases and
      phospholipases. A key role in triggering these indirect events is played by
      Ca(2+) whose cytosolic concentration during oxidative stress raises well above
      the physiological limits.

PMID- 22358960
TI  - DNA and cell death.
AB  - The type of DNA damage and the role of poly (ADP-ribosyl) polymerase (ADPRP) and
      sulphated glyprotein 2 (SGP-2) in programmed cell death (apoptosis) was
      investigated in the following model systems: i) rat thymocytes treated with
      dexamethasone (DEX) eitherin vitro orin vivo; ii) human perypheral blood
      mononuclear cells (hPBMCs) exposed to oxygen free radicals (OR); iii) K562 cell
      line killed by hPBCs during spontaneous (NK) or interleukin-2 (IL-2)-induced
      (LAK) cytotoxic activity. The results suggest that ADPRP and SGP-2 are involved
      in the apoptotic process, but their role probably differs according to the type
      of cell and the inducing damage/stimulus. Moreover, no simple correlation appears
      to exist between the extent of DNA damage and cell survival or cell death.

PMID- 22358961
TI  - Effects of a 50-Hz sinusoidal magnetic field on the dielectric properties of
      chick embryo myoblasts.

PMID- 22358962
TI  - Induction of DNA double strand breaks in cultured mammalian cells exposed to
      hydrogen peroxide and histidine.
AB  - The amino acid histidine was found to increase the toxicity of H(2)O(2) in
      cultured mammalian cells. Histidine also augmented the level of DNA single strand
      breaks (SSB) detectable in cells exposed to the oxidant and, in addition,
      resulted in the appearance of DNA double strand breaks (DSB), a lesion which is
      not produced by H(2)O(2) alone.

PMID- 22358963
TI  - Human immunodeficiency virus (HIV) infection of cell cultures. An ultrastructural
      and immunocytochemical approach.

PMID- 22358964
TI  - On the mode of action ofClostridium difficile toxin A: anin vitro study.
AB  - C. difficile toxin A causes the rounding up and the formation of surface blebs in
      normal rat intestinal crypt cells (IEC-6). These phenomena, together with the
      inhibition of DNA synthesis and the cell lysis, could be the mechanisms leading
      the toxin-treated cells to death.

PMID- 22358965
TI  - Modulation of cytotoxic but not genotoxic effects by dicumarol on mitomycin C
      treated Chinese hamster cells.

PMID- 22358966
TI  - The use of isolated rat hepatocyte couplets, microscopic optical planimetry and
      quantitative microfluorimetry in hepatobiliary physiology.

PMID- 22358967
TI  - Single cell assay with an automated capillary microinjection system.
AB  - An automated capillary microinjection system with computer controlled positioning
      of the cells and of the capillary, and its applications and advantages arc
      described. About 1500 injections are possible in one hour, with high
      reproducibility. In cytoplasmic and nuclear injections more than 90% and 85% of
      the cells are successfully injected. Using FITC-Dextran at a concentration of
      0.5% as a fluorescently labelled coinjection marker, 99% of the cells can be
      retrieved in cultrue medium even 48 hours after unjection. The coordinates of the
      cells are stored in the computer and accuracy in statistical evaluation of
      experiments is improved in coparison to the manual techniques. Methods for
      preparatin and handling of glass capillaries were developed resulting in
      reproducible form and significantly reduced clogging rate. The improved
      characteristics offered by this system are demonstrated in studies leading to the
      confirmation of existence of mRNA(s) inhibiting cell proliferation. Functional
      screening by cell injections of cDNA libraries and of size fractionated mRNA
      molecules can be performed efficiently with the automated microinjection system.

PMID- 22358968
TI  - Fluorimetric approaches to the study of calcium transients in living cells.
AB  - This paper is a short review of the fluorimetric methods used to measure
      intracellular free Ca++ concetration in living cells. The availability of
      fluorescent probes has greatly contributed to the understanding of the mechanisms
      responsible for the cellular homeostasys of this second messenger. Data can be
      collected from populations of cells by spectrofluorimetry or from small groups or
      single cells by spectromicroscopy. Finally the fluorescent images can be captured
      by a high sensitivity camera, digitally processed and convert in Ca++ images of
      the cell. The technique allows recognition of differences in [Ca++]i transients
      among adjacent cells in a same field or in different regions of a cell and
      greatly contributes to the identification of the cellular mechanisms modulating
      [Ca++]i.

PMID- 22358969
TI  - Cell cycle analysis in flow cytometry: Use of BrdU labelling and side scatter for
      the detection of the different cell cycle phases.
AB  - Cell cycle analysis in flow cytometry is based on the incorporation of labelled
      precursors in DNA. The use of BrdU versus SSC, in which side scatter substitutes
      PI fluorescence, has proved to be useful also for the distinction between G2 and
      Mitotic cells. Mitoses often produce an SSC decrease due to the morphological
      changes that happen in the nucleus during this phase of cell cycle. Moreover, DNA
      accessibility to PI varies during mitosis, as well. However, most of these
      variations, detectable by flow cytometry appear to be basically dependent on the
      cell line used.

PMID- 22358970
TI  - Image analysis techniques. The problem of the quantitative evaluation of
      thechromatin ultrastructure.
AB  - The application of image analysis methods to conventional thin sections for
      electron microscopy to analyze the chromatin arrangement are quite limited. We
      developed a method which utilizes freeze-fractured samples; the results indicate
      that the method is suitable for identifying the changes in the chromatin
      arrangement which occur in physiological, experimental and pathological
      conditions. The modern era of image analysis begins in 1964, when pictures of the
      moon transmitted by Ranger 7 were processed by a computer. This processing
      improved the original picture by enhancing and restoring the image affected by
      various types of distorsion. These performances have been allowed by the third
      generation of computers having the speed and the storage capabilities required
      for practical use of image processing algorithms. Each image can be converted
      into a two-dimensional light intensity function: f (x, y), where x and y are the
      spatial coordinates and f value is proportional to the gray level of the image at
      that point. The digital image is therefore a matrix whose elements are the pixels
      (picture elements). A typical digital image can be obtained with a quality
      comparable to monochrome TV, with a 512*512 pixel array with 64 gray levels. The
      magnetic disks of commercial minicomputers are thus capable of storing some
      tenths of images which can be elaborated by the image processor, converting the
      signal into digital form. In biological images, obtained by light microscopy, the
      digitation converts the chromatic differences into gray level intensities, thus
      allowing to define the contours of the cytoplasm, of the nucleus and of the
      nucleoli. The use of a quantitative staining method for the DNA, the Feulgen
      reaction, permits to evaluate the ratio between condensed chromatin (stained) and
      euchromatin (unstained). The digitized images obtained by transmission electron
      microscopy are rich in details at high resolution. However, the application of
      image analysis techniques to these images and especially to those referring to
      nuclei, is limited by several drawbacks: i) the thin section represents only a
      small fraction of the nuclear volume entirely visible in optical microscope
      specimens; ii) the identification of nucleosomes, of the solenoid fibres and of
      the higher levels of compaction of the heterochromatin is not thinsectioned
      specimens; iii) the differences between heterochromatin and euchromatin are based
      only on their grey level but do not reveal possible variations of their
      structural organization. Therefore, the applications of image analysis to the
      nuclear content does not utilzes the high resolution power of e.m. images and
      simply quantify the areas occupied by electron-dense chromatin with respect to
      the more electron-transparent ones. This result is less significative of those
      obtainable by optical microscopy, since the electron staining is not quantitative
      as the Fulgen reaction. On the other hand, the following problems still remain
      unresolved and should be clarified only by the use of quantitative image
      analysis: ultrastructural organization of the different types of heterochromatin
      (1); relationships between gene activation, transcription and chromatin
      decondensation; chromatin arrangement transformation induced by exogenous agents.
      In order to face these problems, in the last years we applied image analysis to
      cell or tissue specimens frozen in liquid nitrogen and then fractured in order to
      expose the inner content of the nucleus (Fig. 1). The obtained metal replicas
      represent very suitable specimens for digitalized image elaboration, since the
      fibers which give rise to the chromatin domains are exposed by the fracturing and
      evidentiated by the shadowing as black dots with a clear white shadow (Fig. 2).
      Therefore, their size and shape can be quantitatively evaluated by a digital
      image processor; in this vay the structural elements of the chromatin fibres are
      also detectable inside a fractured nucleus and their relative percentage ca be
      determined in each nuclear area (Fig. 3). This type of analysis has been
      initially used for characterizing in quantitative terms the organization of the
      nucleolar, heterochromatin and euchromatin areas in isolated nuclei (2) since the
      isolation procedure increases the differences among the nuclear domains. By using
      freeze-fractured isolated nuclei and conventional image analysis procedures, we
      quantitatively described the changes induced in the chromatin superstructure by
      the intercalating dye ethidium bromide (3), by the polyanionic phospholipid
      phosphatidylserine (4) and by the chemical carcinogen diethylnitrosamine (5). In
      all these cases, the principal affected parameter has been the ratio between the
      nucleosome and dolenoid percentage in different nuclear domains. The selection of
      a given class of particles, based on their size and/or shape, allowed to
      determine the spatial localization of some components such as the nuclear matrix,
      not easily detectable with conventional staining methods (6).

PMID- 22358971
TI  - T cell differentiation in the thymus.
AB  - T lymphocytes arise in the thymus and seed to peripheral lymphoid organs as fully
      functional cells at the time of exit. In humans, the thymus begins to function
      very early in ontogeny and releases large numbers of T cells before the time of
      birth. However, the vast majority of developing thymocytes (>95%) die within the
      thymus as a result of stringent selection processes. Positive selection imposes
      self-MHC-restriction on thymocytes and dictates the MHC-restricted repertoire of
      post-thymic T cells. Negative selection results in deletion of autoreactive
      cells. Both types of selection depend on cell to cell contracts and on the
      presence of appropriate growth factors which are still largely undetermined. Cell
      to cell contacts occur between developing thymocytes and cells of the thymic
      microenvironment (accessory cells), and are mediated by several receptor/ligand
      interactions which subserve the function of establishing and stabilizing these
      contacts. Besides MHC-TCR interactions, adhesion molecules are important for
      thymocyte maturation, selection and activation, and for the export and peripheral
      homing of mature T cells produced in the thymus. Here we describe a novel
      integrin involved in thymocyte-thymic epithelial cell interactions.

PMID- 22358972
TI  - Adhesion and activation molecules expressed by human natural killer cells.
AB  - Our study concerns the expression and the regulation of adhesion and activation
      receptors on human NK cells. In particular we provide evidence on: a) the
      expression on fresh human NK cells of VLA-4, VLA-5 and VLA-6, extracellular
      matrix (ECM) receptors of integrin family capable of mediating their adhesion to
      FN and LM; b) the role of PKC on the regulation of CD16, a differentiation
      antigen associated with FcgammaR type III expressed by all NK cells, which
      mediate ADCC activity and trigger lymphokine production.

PMID- 22358973
TI  - Biochemical characterization of NK-subset specific triggering surface molecules.

PMID- 22358974
TI  - IL-2 induces the release of secondary cytokines which stimulate the cytotoxic
      activity of either NK or CD8(+) lymphocytes.

PMID- 22358975
TI  - Enhancing effect ofCandida albicans mannoproteins on the induction of a primary
      antibody response in cultures of human lymphocytes.

PMID- 22358976
TI  - A growth factor different from IL-6 promotes the growth of Epstein-Barr virus
      transformed cells at low cell density.
AB  - Interleukin-6 (IL-6) was recently described to support the growth of Epstein-Barr
      (EBV) transformed lymphocytes. However no effect was reported on cloning of EBV
      transformed lymphocytes under limiting dilution conditions. In this paper we
      demonstrate that the Supernatant of Human Endothelial Cells (HECS) contains a
      factor(s) different from IL-6 which induces high cloning efficiency of EBV
      transformed cell lines, cultured under limiting dilution conditions. Furthermore
      HECS is superior to IL-6 in all the passages of EBV lymphocytes transformation.

PMID- 22358977
TI  - Sequential activation of hormone/cytokines in the stimulation of NK cells: A new
      model of neuroendocrine-immune interaction.

PMID- 22358978
TI  - Selective modulation with liposomes containing Der. P1 labelled with monoclonal
      antibodies.

PMID- 22358979
TI  - Long-term culture of human LAK cells.

PMID- 22358980
TI  - Subpopulations of human NK (CD3-CD16+) lymphocytes identified by monoclonal
      antibodies directed to clonally distributed functional surface molecules.

PMID- 22358981
TI  - Biological inducers of haemopoietic differentiation.

PMID- 22358982
TI  - Role of interferons in cell differentiation and development.
AB  - Interferons (IFNs), besides inducing an antiviral state in uninfected cells, are
      also natural regulatory molecules. They play a key role in the regulation both of
      cell growth and differentiation, and of development. Up-or down-regulation of
      oncogenes by IFNs may be one of the mechanisms by which these molecules affect
      cell physiology. The list of IFN-inducible proteins continues to grow rapidly and
      future research should identify among these the mediators of the biological
      effects of IFNs.

PMID- 22358983
TI  - Cellular interactions and oligodendrocyte differentiation in vitro.
AB  - The aim of the present study was to understand the role of cellular interactions
      in the choice of the oligodendroglial differentiation route by bipotential
      progenitors (O-2A progenitors) of oligodendrocytes (OL) and type-2 astrocytes
      (AS). Cell populations enriched in 0-2A progenitors, obtained from mixed rat
      cortical glial cultures, were subcultured at low density in BME+10% fetal calf
      serum on a poly-L-lysine (PLL) substrate (controls) or on a substrate of purified
      type-1 AS killed by air drying (K-AS), in order to study the interactions between
      the two cell types independently of the soluble mitogen(s) secreted by type-1 AS.
      While on PLL the progenitors differentiated into type-2 AS within a week, on K-AS
      many of them differentiated into OL. However, on K-AS O-2A progenitors
      proliferated more than on PLL, and this proliferation appeared to be related to
      unknown polypeptide components of the extracellular matrix produced by type-1 AS.
      The preferential differentiation of O-2A progenitors into OL on K-AS may thus be
      partly related to the higher density achieved by the cells on this substrate.
      This hypothesis is supported by the observation that purified O-2A progenitors
      subcultured at high density on PLL largely differentiated into OL. The effect of
      cell density on lineage decision appeared to be related to the secretion of high
      molecular weight autocrine differentiation factors by O-2A lineage cells.

PMID- 22358984
TI  - Post-translational modification of spectrin induced by excitatory amino acids in
      cultured cerebellar granule cells.
AB  - We have utilized primary cultures from rat cerebellum, 95% enriched in granule
      cells, to investigate the expression of proteins of the cortical cytoskeleton and
      of the synaptic vesicles and the relationship between excitatory amino acid
      receptors activation and calcium dependent proteolysis of fodrin. Exposure of
      neuronal cell cultures to N-methyl-D-aspartate (NMDA) in the absence of Mg(2+)
      and in the presence of glycine causes the appearance of 150 kDa proteolytic
      fragment (s) of-fodrin as detected by immunoblots. The effect of NMDA on fodrin
      proteolysis is inhibited by the NMDA antagonist 2-amino-5-phosphonovalerate
      (APV), by 3 mM Mg(2+), by calpain I inhibitor and by the omission of
      extracellular calcium. The kainate, at the same concentration of NMDA, is less
      effective and no degradation of fodrin is observed after exposure of cerebellar
      neurons to quisqualate. These findings suggest that calcium/calpain I-dependent
      fodrin proteolysis is selectively associated to the functional activation of NMDA
      receptors.

PMID- 22358985
TI  - In vitro studies on the interactions between antigen-specific T line cells and
      CNS glial cells.

PMID- 22358986
TI  - Effects of triiodothyronine (T3) on differentiation of rat cortical neurons in
      primary cultures.
AB  - Some of the events which characterize neuronal terminal differentiation have been
      studied in rat cortical neurons cultured in a selective synthetic medium for a
      period which corresponds to terminal brain maturation in vivo. In particular, we
      have studied the effect of T3 on the synthesis of nuclear proteins and the
      expression of the mRNAs which encode different variants of T3 nuclear receptors
      (c erb A proteins). We have shown that: a) T3 stimulates the turnover of nuclear
      proteins, with a more evident effect on the non-histone component; b) for the
      whole lifespan of cultures the predominant form of c erb Aalpha mRNA is the
      alpha2 variant (which encodes a protein unable to bind T3); whatever the function
      of alpha2 protein this finding suggests that its predominance on alpha1 is
      settled very early during mammalian brain maturation.

PMID- 22358987
TI  - Expression of interferon genes in murine macrophages: Possible role of endogenous
      interferon in the modulation of cell differentiation.
AB  - The expression of interferon (IFN)-beta gene was studied in mouse peritoneal
      macrophages (PM) harvested from normal mice (lps ( n )) or LPS-hyporesponsive
      mice (lps ( d )). A strong direct correlation between the LPS response of PM and
      their capacity to expressing basal levels of IFN was found. The results suggest
      that the constitutive expression of IFN-beta gene can play an important role not
      only in the resistance to viral infection but also in the modulation of cell
      differentiation.

PMID- 22358988
TI  - CK-MM PGAM-MM G6PD and am biochemical markers of functional innervated cultured
      human muscle fibers.
AB  - RESULTS AND CONCLUSIONS: The biochemical analyses of the total enzymatic
      activities of CK. PGAM in innervated cultures with advanced morphological
      maturation showed a progressive increase up to 60 days after innervation, fetal
      isozyme patterns of CK-BB and PGAM-BB at early stage of innervation and almost
      complete transition of CK and PGAM from BB to MM isozymes in more advanced stage
      of innervation (Figs 1, 2). Time course of G6PD activity in parallel cultures
      showed a higher activity in early stages of myogenesis(myoblastmyotube: 121.4+/
      10 nM/min/mg prot) and in early phase of innervation (30 days after innervation:
      109.66+/-26.10 nM/min/mg prot) with a decline of activity in advanced stage of
      innervation (60 days after innervation: 82.33+/-36.55 nM/min/mg prot) A
      progressive increase of AM activity in mid (30 days after innervation: 1623.66+/
      10.96 pM/min/mg prot) and late stage of innervation (45 days after innervation:
      2150.33+/-568.27 pM/min/mg prot) in comparison with aneural (536+/-107.39
      pM/min/mg prot) was also found our study suggests these enzymes as biochemical
      markers of functional innervation of cultured human muscle fibers.

PMID- 22358990
TI  - Foreword.

PMID- 22358989
TI  - Morphological and biochemical modifications during neuroblastoma cell
      differentiation.
AB  - In order to define some distinctive criteria of differentiation, we studied the
      effects of retinoic acid (RA), gamma-interferon (gamma-IFN), cytosine arabinoside
      (ARA-C), nerve growth factor (NGF), tumor necrosis factor (TNF), and 12-0
      tetradecanoylphorbol-13 acetate (TPA) on the human neuroblastoma cell line, LAN
      5. Intracellular levels of acetylcholinesterase, neuron specific enolase,
      catecholamines, and related neurotransmitters were evaluated after 8 days of
      treatment with various inducers. Our data indicate that the most striking
      biochemical changes accompanying LAN-5 cell differentiation are a shift from a
      catecholaminergic to a cholinergic phenotype, and/or a drastic increase in the
      catecholamines levels. Moreover, small changes may be independent of thein vitro
      maturation. Thus, biochemical phenotyping, more than morphological evaluation, is
      a fruitful approach to monitor neuronal cell differentiation.

PMID- 22358991
TI  - XI National Congress of the Italian Cell Culture Association (AICC) : Rome,
      October 29-31, 1990.

PMID- 22358992
TI  - Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver
      tumor model.
AB  - PURPOSE: The purpose of this study was to study the pharmacokinetics of
      irinotecan injected intravenously, intra-arterially, or loaded onto a delivery
      platform. MATERIAL AND METHODS: Fifty-four New Zealand White rabbits with VX2
      liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either
      by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug
      eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN
      38 concentrations were measured at different time points in serum, tumor, and
      normal liver. RESULTS: Twelve milligrams of irinotecan were injected IV and IA,
      whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan
      reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1
      495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001)
      delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan
      concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan
      levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in
      parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2
      (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h;
      and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02).
      At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for
      IV, IA, and DEBIRI, respectively (P = 0.03). CONCLUSION: Compared with IV or IA,
      DEBIRI induces lower early serum levels of irinotecan, a high and prolonged
      intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h.
      Further evaluation of the clinical benefit of DEBIRI is warranted.

PMID- 22358993
TI  - Prospective evaluation of transcatheter arterial chemoembolization (TACE) with
      multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil)
      compared with TACE with epirubicin for treatment of hepatocellular carcinoma.
AB  - PURPOSE: To compare the efficacy of transcatheter arterial chemoembolization
      (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5
      furuorouracil: Multi group) with TACE using epirubicin (EP group) for
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The study design was a
      single-center, prospective, randomized controlled trial. Patients with
      unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation,
      were assigned to the Multi group or the EP group. We assessed radiographic
      response as the primary endpoint; secondary endpoints were progression-free
      survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage
      or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion;
      Grades II and III indicated significant hepatic artery damage). A total of 51
      patients were enrolled: 24 in the Multi group vs. 27 in the EP group. RESULTS: No
      significant difference in HCC patient background was found between the groups.
      Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs.
      EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and
      76%, respectively, with no significant difference. Significantly greater Grade 3
      transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery
      abnormality was observed in 34% of the Multi group and in 17.1% of the EP group
      (p = 0.019). CONCLUSION: TACE with multiple anti-cancer drugs was tolerable but
      appeared not to contribute to an increase in radiographic response or PFS, and
      caused significantly more hepatic arterial abnormalities compared with TACE with
      epirubicin alone.

PMID- 22358994
TI  - The effect of endovascular revascularization of common iliac artery occlusions on
      erectile function.
AB  - PURPOSE: To determine the incidence of erectile dysfunction in patients with
      common iliac artery (CIA) occlusive disease and the effect of revascularization
      on erectile function using the sexual health inventory for males (SHIM)
      questionnaire. METHODS: All patients (35 men; mean age 57 +/- 5 years; range 42
      67 years) were asked to recall their sexual function before and 1 month after
      iliac recanalization. Univariate and multivariate analyses were performed to
      determine variables effecting improvement of impotence. RESULTS: The incidence of
      impotence in patients with CIA occlusion was 74% (26 of 35) preoperatively.
      Overall 16 (46%) of 35 patients reported improved erectile function after iliac
      recanalization. The rate of improvement of impotence was 61.5% (16 of 26 impotent
      patients). Sixteen patients (46%), including seven with normal erectile function
      before the procedure, had no change. Three patients (8%) reported deterioration
      of their sexual function, two of whom (6%) had normal erectile function before
      the procedure. The median SHIM score increased from 14 (range 4-25) before the
      procedure to 20 (range 1-25) after the procedure (P = 0.005). The type of
      recanalization, the age of the patients, and the length of occlusion were related
      to erectile function improvement in univariate analysis. However, these factors
      were not independent factors for improvement of erectile dysfunction in
      multivariate analysis (P > 0.05). CONCLUSION: Endovascular recanalization of CIA
      occlusions clearly improves sexual function. More than half of the patients with
      erectile dysfunction who underwent endovascular recanalization of the CIA
      experienced improvement.

PMID- 22358995
TI  - Elevated CO2 interacts with herbivory to alter chlorophyll fluorescence and leaf
      temperature in Betula papyrifera and Populus tremuloides.
AB  - Herbivory can influence ecosystem productivity, but recent evidence suggests that
      damage by herbivores modulates potential productivity specific to damage type.
      Because productivity is linked to photosynthesis at the leaf level, which in turn
      is influenced by atmospheric CO(2) concentrations, we investigated how different
      herbivore damage types alter component processes of photosynthesis under ambient
      and elevated atmospheric CO(2). We examined spatial patterns in chlorophyll
      fluorescence and the temperature of leaves damaged by leaf-chewing, gall-forming,
      and leaf-folding insects in aspen trees as well as by leaf-chewing insects in
      birch trees under ambient and elevated CO(2) at the aspen free-air CO(2)
      enrichment (FACE) site in Wisconsin. Both defoliation and gall damage suppressed
      the operating efficiency of photosystem II (PhiPSII) in remaining leaf tissue,
      and the distance that damage propagated into visibly undamaged tissue was
      marginally attenuated under elevated CO(2). Elevated CO(2) increased leaf
      temperatures, which reduced the cooling effect of gall formation and freshly
      chewed leaf tissue. These results provide mechanistic insight into how different
      damage types influence the remaining, visibly undamaged leaf tissue, and suggest
      that elevated CO(2) may reduce the effects of herbivory on the primary
      photochemistry controlling photosynthesis.

PMID- 22358996
TI  - Litter quality and inflammatory response are dependent on mating strategy in a
      reptile.
AB  - Maintenance of health and the production of offspring are competing processes
      that can result in trade-offs. As vertebrates invest substantial resources in
      their immune system, it is crucial to understand the interactions between
      immunity and reproductive strategies. In the lizard Zootoca vivipara, females
      have condition- and context-dependent mating strategies. We predicted that, if
      the risk of infection is higher for polyandrous females, then polyandrous females
      should invest more in immune system while monandrous females should invest more
      in reproduction. In order to test our prediction, we captured 62 gravid females
      of known age in a natural population; we kept them until parturition to access to
      their offspring. Then, using microsatellite marker-based paternity analyses
      within litters, we determine the mating strategy of females (monandrous or
      polyandrous). Females were also challenged with PHA to estimate their
      inflammatory response. Our results show that polyandrous females have a higher
      PHA response than the monandrous females, and that monandrous females produce
      more males and more juveniles of better body condition than polyandrous females.
      The relationship between mating behaviour and immune function may have
      consequences for females and may shape the evolution of mating systems.

PMID- 22358997
TI  - Interactive influence of biotic and abiotic cues on the plasticity of preferred
      body temperatures in a predator-prey system.
AB  - The ability to modify phenotypes in response to heterogeneity of the thermal
      environment represents an important component of an ectotherm's non-genetic
      adaptive capacity. Despite considerable attention being dedicated to the study of
      thermally-induced developmental plasticity, whether or not interspecific
      interactions shape the plastic response in both a predator and its prey remains
      unknown. We tested several predictions about the joint influence of predator/prey
      scents and thermal conditions on the plasticity of preferred body temperatures (T
      (p)) in both actors of this interaction, using a dragonfly nymphs-newt larvae
      system. Dragonfly nymphs (Aeshna cyanea) and newt eggs (Ichthyosaura alpestris)
      were subjected to fluctuating cold and warm thermal regimes (7-12 and 12-22
      degrees C, respectively) and the presence/absence of a predator or prey chemical
      cues. Preferred body temperatures were measured in an aquatic thermal gradient (5
      33 degrees C) over a 24-h period. Newt T (p) increased with developmental
      temperature irrespective of the presence/absence of predator cues. In
      dragonflies, thermal reaction norms for T (p) were affected by the interaction
      between temperature and prey cues. Specifically, the presence of newt scents in
      cold regime lowered dragonfly T (p). We concluded that predator-prey interactions
      influenced thermally-induced plasticity of T (p) but not in a reciprocal fashion.
      The occurrence of frequency-dependent thermal plasticity may have broad
      implications for predator-prey population dynamics, the evolution of thermal
      biology traits, and the consequences of sustaining climate change within
      ecological communities.

PMID- 22358998
TI  - DART-Orbitrap MS: a novel mass spectrometric approach for the identification of
      phenolic compounds in propolis.
AB  - This is the first direct analysis in real-time mass spectrometry (DART-MS) study
      of propolis and a first study on the analysis of bee products using high
      resolution DART-MS (DART-HRMS). Identification of flavonoids and other phenolic
      compounds in propolis using direct analysis in real-time coupling with Orbitrap
      mass spectrometry (DART-Orbitrap MS) was performed in the negative ion mode for
      minimizing the matrix effects, while the positive ion mode was used for the
      confirmation of selected compounds. Possible elemental formulae were suggested
      for marker components. The duration of one sample analysis by DART-MS analysis
      lasted ca. 30 s, and all benefits of high-resolution mass spectrometry were used
      upon data processing using the coupling of DART with the Orbitrap mass
      spectrometer. The possibility for scanning analysis of dried propolis extract
      spots on a planar porous surface was investigated in the heated gas flow of the
      DART ion source with adjustable angle. As an independent method, the approach of
      scanning analysis is of high interest and of future potential for confirmation of
      the results obtained from liquid sample analysis. Scanning analysis is highly
      promising for further development in the bioanalytical field due to the
      convenience of the storage and transportation of dried sample spots.

PMID- 22358999
TI  - Label-free quantification using MALDI mass spectrometry: considerations and
      perspectives.
AB  - Profound knowledge of protein abundances in healthy tissues and their changes in
      disease is crucial for understanding biological processes in basic science and
      for the development of novel diagnostics and therapeutics. Mass spectrometrybased
      label-free protein quantification is used increasingly often to gain insights
      into physiological changes observed in perturbed systems. Although the soft
      ionization techniques electrospray ionization and matrix-assisted laser
      desorption/ionization have both been used for protein quantification, this
      article focuses on instrumental setups with a MALDI ion source. Beside reviewing
      current bioinformatic data-processing tools for label-free quantification and
      elaborating on the technical benefits of combining UHPLC and MALDI-MS, we outline
      the potential of state-of-the-art instruments by reporting unpublished results
      obtained from twenty-four complex biological samples. This review points out that
      the capabilities of LC-MALDI MS systems have not yet been fully utilized because
      of a lack of suitable software tools.

PMID- 22359000
TI  - Hematopoietic cell transplantation for tolerance induction.

PMID- 22359001
TI  - Stimulation of liver functions in hierarchical co-culture of bone marrow cells
      and hepatocytes.
AB  - A hierarchial co-culture, in which rat hepatocytes and non-parenchymal liver
      cells (NPLCs) were separated by a collagen layer and which was designed to mimic
      the in vivo microenvironment, was carried out with the aim of developing a module
      for bio-artificial liver support. Compared with a monolayer co-culture and
      hepatocytes cultured alone in a monolayer, higher urea synthesis activity was
      maintained for 6 d in the hierarchical co-culture. When a rat hepatoma cell line
      H4-II-E-C3, which retains the induction of tyrosine aminotransferase (TAT), was
      co-cultured in a monolayer with NPLCs, dose-dependent stimulation of TAT
      induction was observed. In a hierarchical co-culture, NPLCs further stimulated
      TAT induction in H4-II-E-C3 cells. Since peritoneal macrophages could stimulate
      TAT induction in hepatocytes in both monolayer and hierarchical co-cultures, bone
      marrow cells, which can proliferate and differentiate into macrophages in vitro,
      were investigated as a possible substitute for NPLCs. Bone marrow cells isolated
      from rat femurs were cultivated in the presence of IL-3 and macrophage colony
      stimulating factor (M-CSF), and co-cultured with hepatocytes. Urea synthesis and
      TAT induction of hepatocytes were stimulated in the co-culture. The co-culture of
      bone marrow and H4-II-E-C3 cells, both of which have proliferation ability in
      vitro, was also shown to be effective in stimulating liver functions. The
      hierarchical configuration, in which two cell types can communicate with the
      soluble factor(s) through a collagen layer, was found to be more effective than a
      monolayer in long-term co-culture.

PMID- 22359002
TI  - Growth stimulation of tumor-specific cytotoxic T lymphocytes on concanavalin a
      immobilized carrier beads.
AB  - Human tumor-specific CD4(+) cytotoxic T lymphocytes (CTL) were generated against
      duodenum papilloma cell line TGBC18TKB from HLA type-matched peripheral blood
      mononuclear cells. Concanavalin A (Con A) immobilized on carrier beads stimulated
      growth of the CTL in a long-term culture without repeated antigen stimulation,
      while soluble Con A induced death of the CTL. The CTL exhibited the target
      specific cytotoxicity in a more potent manner than those before the long-term
      culture in the presence of the immobilized Con A. Enhanced expression of the
      adhesion molecule, CD11b, was observed on the CTL. These results suggest that
      immobilized Con A will be useful for continuous growth stimulation and large
      scale expansion of CTL without tumor antigen.

PMID- 22359003
TI  - Stimulation of cell growth in the U-937 human myeloid cell line by honey royal
      jelly protein.
AB  - Royal jelly was fractionated by ion-exchange chromatography and a protein (DIII
      protein) that had growth stimulating activity to the U-937 human myeloid cell
      line was obtained. The molecular weight of the DIII protein was 58 kDa on SDS
      PAGE. The growth stimulating activity of the DIII protein was shown to be
      relatively heat and pH stable.

PMID- 22359004
TI  - The myofibroblast markers alpha-SM actin and beta-actin are differentially
      expressed in 2 and 3-D culture models of fibrotic and normal skin.
AB  - To characterize the differences between fibrotic myofibroblasts and normal
      fibroblasts, we studied two differentiation markers: alpha-smooth muscle (SM)
      actin, a specific marker of myofibroblast differentiation, and beta-actin, which
      is overexpressed in the fibrotic tissue. Experiments were performed on
      fibroblasts isolated from normal pig skin and on subcutaneous myofibroblasts
      isolated from pig radiation-induced fibrosis. Three culture models were used:
      cells in monolayers, equivalent dermis, consisting of fibroblasts embedded into a
      matrix composed of type I collagen, and in vitro reconstituted skin, in which the
      matrix and containing life fibroblasts were overlaid with keratinocytes. Samples
      were studied using immunofluorescence and western-blotting. In monolayers
      cultures, both fibrosis and normal cells expressed alpha-SM actin. Furthermore,
      similar amounts of beta-actin protein were found. In these conditions, the
      resulting alterations in the phenotypes of cells made comparison of cultured
      fibrotic and normal cells irrelevant. Under the two 3-D culture models, normal
      fibroblasts no longer expressed alpha-SM actin. They expressed beta-actin at the
      basal level. Moreover, the fibrotic myofibroblasts in both 3-D models retained
      their differentiation features, expressing alpha-SM actin and overexpressing beta
      actin. We found that this normalization was mainly related to the genomic
      programmation acquired by the cells in the tissue. Cellular motility and
      microenvironment were also involved, whereas cellular proliferation was not a
      major factor. Consequently, both three-dimensional models allowed the study of
      radiation-induced fibrosis in vitro, provided good extrapolations to in vivo
      conditions and avoided certain of culture artefacts.

PMID- 22359005
TI  - Calcium-phosphate mediated DNA transfer into HEK-293 cells in suspension: control
      of physicochemical parameters allows transfection in stirred media. Transfection
      and protein expression in mammalian cells.
AB  - This is the first report of transient transfection of suspended cells with
      purified plasmid DNA in bioreactors or spinner flasks. DNA/calcium phosphate
      complexes were pumped or injected directly into stirred cultures of the
      immortalized human embryo kidney cell line 293 (HEK-293) which had been adapted
      to growth in suspension. We identified culture conditions suitable for this
      approach and modified the protocol for the generation of precipitate complexes,
      based on our earlier work. In order to stabilize the 'DNA-vehicle'-complex in the
      culture medium, we identified pH ranges and ion-concentrations which prevent
      dissolution or aggregation of the precipitate particles. Such conditions
      maintained suspended fine particles in spinners or bioreactors for up to 6 hr.
      During that period, cells and precipitate complexes interacted sufficiently to
      allow DNA transfer and subsequent expression of recombinant protein. In a simple
      5 day batch process, with a starting density of 0.3 * 10(6) cells mL(-1), about
      0.5 mg L(-1) of a recombinant tissue plasminogen activator variant was observed.

PMID- 22359006
TI  - The use of a conventional tissue culture plate as an optically accessible
      perfusion chamber for in situ assays and for long-term cultivation of mammalian
      cells.
AB  - An alternative culture system has been developed based on a conventional tissue
      culture plate (3.5 cm diameter) which is changed into a closed perfusion chamber.
      The system can easily be scaled up from one to several chambers. The shape and
      the size of the area of cell growth may be designed to individual experimental
      demands. The whole culture chamber is optically accessible, so cell growth and
      morphology can be evaluated by light microscopy. Furthermore the cellular
      physiology can be characterised by any fluorimetric assay using a bottom type
      fluorescence reader. A peristaltic pump sustains a constant medium flow through
      the chamber thus creating true homeostasis. The use of HPLC-valves and connectors
      allows the switching between different media or assay solutions. Thus it is
      possible to perform in situ assays also measuring transient effects. A protocol
      for vitality tests using calcein-AM is worked out for an adherent cell line and
      for a suspension cell line. The lower detection limits are 7 * 10(2) cells cm(-2)
      for the adherent cells and 5 * 10(4) cells mL(-1) for the suspension cells. The
      upper limits are 1-2 * 10(5) cells cm(-2) respectively 8 * 10(6) cells mL(-1).

PMID- 22359007
TI  - Adaptation of BHK cells producing a recombinant protein to serum-free media and
      protein-free medium.
AB  - In this work a recombinant BHK21 clone producing a fusion protein with potential
      application in tumour target therapy was adapted to five different serum-free
      media (SFM) and to a protein-free medium (PFM). Only the PFM did not require a
      gradual adaptation to cell growth in the absence of serum. All tested SFM
      required a gradual adaptation (up to 35 days). For the majority of the SFM
      tested, cell specific productivity was not affected by the decrease in serum
      concentration during adaptation; however, cell growth was significantly affected
      by the serum decrease. Both cell growth and productivity were increased when PFM
      SMIF6 was used instead of the control medium. Long term measurements
      (approximately 100 days) of cell specific productivity for PFM and the two best
      SFM showed that productivity was maintained. This indicates the media capability
      to be used in long term production processes.

PMID- 22359008
TI  - Gene transfection of multicellular spheroid of hepatocytes on an artificial
      substrate.
AB  - The handling of hepatocytes, a major cell population in the liver, is an
      important technique in both liver tissue engineering and hepatology. However,
      these cells are so fragile that it has been impossible to harvest hepatocytes
      with high viability from tissue culture dishes after a period of culture in
      vitro. In this study, we employed an artificial substrate for transfection of
      multilayer hepatocytes and harvested these cells with high viability after
      transfection. Hepatocytes cultured on an amphiphilic artificial substrate form
      multilayer aggregates (spheroids) in the presence of growth factors during gene
      transfection with cation liposomes. Compared to cells cultured on a collagen
      coated plate, these spheroids are easily harvested with high viability by
      pipetting in EDTA solution. In addition, these spheroids rapidly spread on
      collagen after transfer from the artificial substrate, demonstrating that
      hepatocytes in the center of the spheroids were viable. Epidermal growth factor
      (EGF) increased the transfection efficiency into hepatocytes while hepatocyte
      growth factor (HGF) alone did not increase the efficiency. However, HGF
      synergestically increased the effect of EGF on transfection. Interestingly, this
      transfection required the process of spheroid formation because the gene was not
      transfected once the spheroid formation completed or under conditions where
      hepatocytes did not form spheroids. This method using spheroidal hepatocytes for
      in vitro transfection is promising for the development of ex vivo gene therapy.

PMID- 22359009
TI  - Erratum: Establishing apoptosis resistant cell lines for improving protein
      productivity of cell culture.
AB  - Cytotechnology 23 : 55-59, 1997.The correct version of authors list should read:
      Eiji Suzuki(1)-, Satoshi Terada(1), Hiroshi Ueda(1), Tetsuo Fujita(1), Tomoaki
      Komatsu(1), Yon Hui Kim(1), Shinichi Takayama(2), and John C. Reed(2).

PMID- 22359011
TI  - Fastin situ determination of the biomass of anchorage-dependent cells.
AB  - The lengthy and cumbersome protocol used to establish the growth kinetics
      characteristics of anchorage-dependent cells (ADC's)in situ (i.e. while the cells
      adhere on their microsupport) by Aperture Impedance Pulse Spectroscopy (AIPS) can
      be replaced by an accelerated procedure. This we have named Turbo AIPS whereby
      the same results can be obtained without actually performing the manipulations
      leading to the determination of the biomass.

PMID- 22359010
TI  - The prophylactic use of antibiotics in cell culture.
AB  - This article describes the historical development of the prophylactic use of
      antibiotics in cell culture as well as their effects on cells. The influence of
      antibiotics on cell morphology, cellular degeneration and cell death and cellular
      function is summarized. Cellular DNA as well as protein synthesis are affected
      which can lead to interference with, or even changes in, metabolic processes.
      Such effects must be considered in cell culture research. As antibiotics are used
      in multifold ways, the otherwise standardized conditions in cell culture are no
      longer comparable. The prophylactic use of antibiotics is rejected for scientific
      reasons.

PMID- 22359012
TI  - Improvement of the culture stability of non-anchorage-dependent animal cells
      grown in serum-free media through immobilization.
AB  - A murine hybridoma cell line producing a monoclonal antibody against penicillin-G
      amidase and a murine transfectoma cell line secreting a monovalent chimeric
      human/mouse Fab-antibody fragment were cultivated in three different media (serum
      containing, low protein serum-free, and iron-rich protein-free) in flask
      cultures, stirred reactors and a fixed bed reactor. In static batch cultures in
      flasks both cell lines showed similar good growth in all three media.In
      suspension in a stirred reactor, the hybridoma cell line could be cultivated
      satisfactory only in serum-containing medium. In low protein serum-free medium,
      Pluronic F68 had to be added to protect the hybridoma cells against shear stress.
      But even with this supplement only batch, not chemostat mode was possible. In
      iron-rich protein-free medium the hybridoma cells grew also in continuous
      chemostat mode, but the stability of the culture was low. The transfectoma cell
      line did not grow in stirred reactors in any of the three media.Good results with
      both cell lines were obtained in fixed bed experiments, where the cells were
      immobilized in macroporous Siran((r))-carriers. The media, which were optimized
      in flask cultures, could be used without any further adaptation in the fixed bed
      reactor. Immobilization improved the stability and reliability of cultures of non
      adherent animal cells in serum-free media tremendously compared to suspension
      cultures in stirred reactors. The volume-specific glucose uptake rate, an,
      indicator of the activity of the immobilized cells, was similar in all three
      media. Deviations in the metabolism of immobilized and suspended cells seem to be
      mainly due to low oxygen concentrations within the macroporous carriers, where
      the cells are supplied with oxygen only by diffusion.

PMID- 22359013
TI  - DNA fingerprint analysis for the detection of induced mutations in mammalian
      cells in culture.
AB  - A mutation assay in cultured mammalian cells based on the direct analysis of
      minisatellite DNA was developed. Band pattern variations reflect DNA alterations
      ranging from single base changes to complex rearrangements. By DNA fingerprinting
      a large number of autosomal loci throughout the human genome can be
      simultaneously checked, therefore minimizing the size of the samples of cell
      colonies to be scored in the absence of phenotypic selection. For the mutation
      assay chinese hamster cells (V79) were treated with Nitrosoguanidine and 14
      independent colonies were isolated and expanded. DNA fingerprints were obtained
      after digestion of the DNA extracted from each clone with bothHinfI andHae III,
      and hybridisation with both 33.15 and 33.6 probes. Twelve colonies from untreated
      cells were also analysed. Several differences in the band pattern of treated
      colonies were observed when compared with untreated cells; digestion withHae III
      and hybridisation with 33.15 probe allowed the detection of the highest frequency
      of induced variants. The results suggest that minisatellite sequences are
      hypermutable sites that can be used to monitor the mutagenic potential of
      chemical agents directly at the DNA level, without phenotypic selection.
      Moreover, with the method herein decribed, it is possible to distinguish between
      true mutations and epimutations, such as those caused by changes in DNA
      methylation.

PMID- 22359014
TI  - Lack of effect of thrombin on fibrin(ogen)-endothelial cell interaction.
AB  - In the present study we investigate the fibrin(ogen)-endothelial cell binding and
      the effect of thrombin on the endothelial cells in relation to fibrin(ogen)
      binding capacity. Endothelial cell fibrinogen binding was concentration and time
      dependent, reaching saturation at 1.4 MUM of added ligand. At equilibrium, the
      number of fibrinogen molecules bound per endothelial cell in the monolayer was
      5.8+/-0.7*10(6). When endothelial cells were activated by different
      concentrations of thrombin (0-0.1 NIH units ml(-1)), no increase in fibrinogen
      binding capacity was observed at all the thrombin concentration tested. Whereas
      disruption of endothelial cell monolayers was observed at thrombin concentrations
      higher than 0.05 NIH units ml(-1), no increase in the amount of fibrinogen bound
      was observed. Therefore, resting and thrombin-activated endothelial cells show
      the same fibrinogen binding capacity.The adhesion of endothelial cells in
      suspension on immobilized fibrinogen or fibrin was studied to ascertain whether
      the behavior of fibrin is similar to that of fibrinogen. The extent of
      endothelial cell attachment to immobilized fibrinogen and fibrin was similar
      (4275+/-130 cells cm(-2) for fibrinogen and 4350+/-235 cells cm(-2) for fibrin)
      and represent approximately 40% of the added endothelial cells. However,
      endothelial cell adhesion to immobilized fibrin was significantly faster than
      endothelial cell adhesion to immobilized fibrinogen. The maximum binding rate was
      66+/-9 and 46+/-8 cells cm(-2) min(-1) for fibrin and fibrinogen, respectively.
      Therefore, the fibrinopeptides released by thrombin from fibrinogen induce
      qualitative changes which enhance the fibrin interaction with the endothelial
      cells.

PMID- 22359015
TI  - Effect of serum type and concentration on the expression ofbeta-galactosidase in
      recombinant vaccinia virus infected HeLa S3 cells.
AB  - The effect of serum type and concentration on recombinant protein expression in
      vaccinia virus infected HeLa S3 cells was studied in both static and suspension
      culture. A model heterologous protein,beta-galactosidase (beta-gal), was used.
      Calf and horse sera in the range of 0.5-10%(v/v) were investigated. In static
      culture, the calf serum concentration did not show any significant influence on
      the beta-gal production which was almost completed within 24h postinfection (pi).
      Higher horse serum concentration, on the other hand, resulted in higher beta-gal
      concentration which continued to increase until 48 h pi. Total beta-gal
      concentrations in 0.5% calf serum at 24 h pi and 10% horse serum at 48 h pi were
      2.2+/-0.7 and 2.2+/-0.1 IU/ml, respectively. In suspension culture, both sera
      showed their respective effects on the beta-gal production similar to those
      observed in static culture, indicating that the cultivation method had little
      influence on beta-gal production. Accordingly, the use of 0.5% calf serum after
      virus infection in recommended for economical beta-gal production.

PMID- 22359016
TI  - Microcarrier culture: A different approach to granulosa cell cultivation.
AB  - Granulosa cells (GC) are steroid secreting and hormone responsive cells
      synthesizing increased amounts of progesterone (P(4)) under the influence of
      gonadotropins. Up to now these cells have been cultivated as monolayers. However,
      in this system, cells dedifferentiate early and cease to respond to stimulation.
      GC are a good model for studying hormonal regulation of ovarian cell function. In
      this study, microcarrier culture was tested for the first time to see whether it
      would be a good system in which GC would grow and give a stronger responsivity to
      gonadotropins. Cells were grown in stationary culture on microcarriers Cytodex 3
      (C3) coated with collagen and on pure gelatin beads. Only C3 cultures were
      successful. Cells proliferated better on C3 microcarriers and on day 4 of culture
      secreted more P(4) under the influence of FSH and LH than comparative monolayer
      cultures.

PMID- 22359018
TI  - List of authors and chairmen.

PMID- 22359019
TI  - Table of sessions.

PMID- 22359017
TI  - A real-time biomonitoring system to detect arsenic toxicity by valve movement in
      freshwater clam Corbicula fluminea.
AB  - Arsenic (As) is the element of greatest ecotoxicological concern in aquatic
      environments. Effective monitoring and diagnosis of As pollution via a biological
      early warning system is a great challenge for As-affected regions. The purpose of
      this study was to synthesize water chemistry-based bioavailability and valve
      daily rhythm in Corbicula fluminea to design a biomonitoring system for detecting
      waterborne As. We integrated valve daily rhythm dynamic patterns and water
      chemistry-based Hill dose-response model to build into a programmatic mechanism
      of inductance-based valvometry technique for providing a rapid and cost-effective
      dynamic detection system. A LabVIEW graphic control program in a personal
      computer was employed to demonstrate completely the functional presentation of
      the present dynamic system. We verified the simulated dissolved As concentrations
      based on the valve daily rhythm behavior with published experimental data.
      Generally, the performance of this proposed biomonitoring system demonstrates
      fairly good applicability to detect waterborne As concentrations when the field
      As concentrations are less than 1 mg L(-1). We also revealed that the detection
      times were dependent on As exposure concentrations. This biomonitoring system
      could particularly provide real-time transmitted information on the waterborne As
      activity under various aquatic environments. This parsimonious C. fluminea valve
      rhythm behavior-based real-time biomonitoring system presents a valuable effort
      to promote the automated biomonitoring and offers early warnings on potential
      ecotoxicological risks in regions with elevated As exposure concentrations.

PMID- 22359020
TI  - Studies on human urothelial cells propagated in vitro.

PMID- 22359021
TI  - Cytotechnology.

PMID- 22359022
TI  - Cytoskeleton-modulation in growth and development.

PMID- 22359023
TI  - Cellular ageing in vitro.

PMID- 22359024
TI  - Organ development and organotypic culture.

PMID- 22359025
TI  - Cellular transformation by chemicals and oncogernes gene transfer and phenotypic
      changes.

PMID- 22359026
TI  - Cultures of haemopoietic cells: principles and applications.

PMID- 22359028
TI  - Nervous system.

PMID- 22359027
TI  - Tumor cell cultures: Characterization and chemosensitivity.

PMID- 22359029
TI  - Applied skin culture models.

PMID- 22359030
TI  - Cartilage and bone culture.

PMID- 22359031
TI  - Motility and invasion.

PMID- 22359032
TI  - Reorganization of the cytoskeleton of endocrine cells in response to hormones.

PMID- 22359033
TI  - Endothelial and smooth muscle cell culture.

PMID- 22359034
TI  - Production of biologicals using large scale culture.

PMID- 22359035
TI  - In vitro pharmacotoxicology.

PMID- 22359036
TI  - Serum free media.

PMID- 22359037
TI  - Clinical cytology and physiology.

PMID- 22359040
TI  - Mass culture of mammalian cells as a national project.

PMID- 22359038
TI  - beta-1,4-Galactosyltransferase I involved in Schwann cells proliferation and
      apoptosis induced by tumor necrosis factor-alpha via the activation of MAP
      kinases signal pathways.
AB  - beta-1,4-galactosyltransferase-I (beta-1,4-GalT-I) plays a critical role in the
      initiation and maintenance of peripheral nervous system inflammatory reaction.
      However, the exact function of beta-1,4-GalT-I in the regulation of SCs
      proliferation and apoptosis remains unclear. In this study, we found that low
      concentration of tumor necrosis factor-alpha (TNF-alpha) induced SCs
      proliferation, while high concentration of TNF-alpha induced SCs apoptosis.
      Meanwhile, the expressions of beta-1,4-GalT-I, TNFR1, and TNFR2 were changed
      following. When beta-1,4-GalT I overexpression, low concentration of TNF-alpha
      induced SCs proliferation was partially repressed. Concurrently, the activity of
      ERK1/2 was decreased. While knocking down beta-1,4-GalT I expression, high
      concentration of TNF-alpha-induced SCs apoptosis was partially rescued.
      Consistent with this, the activity of P38 and JNK were decreased. We also found
      anti-TNFR2 antibody suppressed low concentration of TNF-alpha-induced SCs
      proliferation, while anti-TNFR1 antibody inhibited high concentration of TNF
      alpha-induced SCs apoptosis. Thus, present data show that beta-1,4-GalT I may
      play an important role in SCs proliferation and apoptosis induced by TNF-alpha
      via different signal pathways and TNFR.

PMID- 22359042
TI  - Introduction.

PMID- 22359041
TI  - Japanese animal cell biotechnology opens to the world.

PMID- 22359043
TI  - Establishment of vascular endothelial cell lines in a serum-free culture and the
      discovery of endothelin and a Vasoactive Intestinal Contractor (VIC).
AB  - Immortal vascular endothelial cell lines were established and utilized for the
      production of an endothelium-derived contraction factor (EDCF) in a serum-free
      medium. After the discovery of Endothelin (21 amino acid peptide, ET) as an EDCF,
      a prepro ET cDNA isolated from human tissue was used to examine the expression of
      ET and its regulation in human endothelial cells. A gene family of ET was shown
      in mouse by using prepro ET cDNA as a probe. Thus, a novel peptide, Vasoactive
      Intestinal Contractor (VIC) homologous to ET was deduced from the sequence of one
      of these genes. VIC was confirmed to induce vasocontraction as well as intestinal
      contraction. Northern blot analysis indicated that this gene was expressed in the
      intestine but not in endothelial cells. A cloning and sequencing of prepro VIC
      cDNA from mouse intestine suggest that a VIC-like peptide, as well as VIC, are co
      synthesized by cleavage from prepro VIC with 160 amino acids.

PMID- 22359044
TI  - Optimization of cell culture conditions for production of biologically active
      proteins.
AB  - We investigated the basic technology of cell culture conditions for production of
      useful substances such as cytokines, and related proteins produced by Namalwa
      cells. Namalwa cells (Klein, 1972), human B lymphoblastoid cells, were used for
      large scale production of alpha-interferon (Klein, 1979). Namalwa KJM-1, a
      subline of Namalwa cells, adapted to serum- and albumin-free medium, can grow at
      a high density above 1 * 10(7) cells/ml in suspension mode by the use of a
      perfusion culture system, Biofermenter(TM), containing a cone-type cell
      sedimentation column as cell separator (Sato, 1983).Several kinds of cytokine
      cDNA can be introduced and expressed in Namalwa KJM-1 cells (Miyaji, 1990a,b,c).
      Some of these were produced in large quantities by use of a gene amplification
      method with dhfr (Miyaji, 1990c), even though the Namalwa KJM-1 cells contained
      endogenous dhfr genes. For stable production of the target protein, Namalwa KJM-1
      cells are very useful host cells, because they have no effective endogenous
      protease activity in the conditioned medium.Using Biofermenter with micro
      silicone fibers and a dialysis system, the specific productivity of the target
      proteins was not depressed at a high cell density.

PMID- 22359045
TI  - Development of a serum-free and heat-sterilizable medium and continuous high
      density cell culture.
AB  - We tried to establish a new serum-free and heat-sterilizable medium, based on our
      serum-free medium in which many lymphoblastoid cells and hybridoma could grow as
      well as in a conventional serum-containing medium.As is well-known, L-glutamine
      (L-Gln) is one of the most heat-labile but essential components for cell growth.
      As a substitute for L-Gln, dipeptide such as Gly-L-Gln or L-Ala-L-Gln, which was
      quite stable even after autoclaving, was found to be utilizable for mammalian
      cell growth. The L-Gln dipeptide-containing serum-free medium was quite stable in
      a solution even after storing at 37 degrees C for 4 months. In the serum-free
      medium containing L-Ala-L-Gln, mouse hybridola could grow and produce more
      antibody than in RPMI 1640+10% FBS.It has been proved that BSA and transferrin,
      which are also heat-labile but essential for the growth of various cell lines,
      can be substituted by heat-stable alpha-cyclodextrin and cholesterol, and Fe
      gluconate, respectively. Insulin has also proved to be heat stable in a solution
      of Fe-gluconate. We thus established a new serum-free medium, all the components
      of which could be heat-sterilizable.Moreover, by adding EGF and BSA but without
      the adhesion factor included in FBS, the serum-free medium was found to support a
      long-term serial culture of a human diploid fibroblast.Finally, with this
      auotoclavable serum-free medium in a perfusion culture apparatus, we were able to
      continuously cultivate a human lymphoblastoid cell line. The production rate of
      IgM was found to be markedly increased by feeding the serum-free medium enriched
      by glucose, bicarbonate, L-Cys, and approtinin. The cell density reached as high
      as 2*10(8)/ml in the serum-free medium. Although the working volume in the
      reactor was only 1 1, the rate of IgM production reached 480 mg/day.The new heat
      sterilizable serum-free medium has several advantages, because L-Gln peptide is a
      heat-stable and available precursor of L-Gln.

PMID- 22359046
TI  - Effective production of anti-tetanus toxoid and anti-HBsAg human monoclonal
      antibodies by serum-free culture of hybridomas.
AB  - Two hybridoma systems, mouse.human-human (m.h-h) heterohybridoma and human-human
      (h-h) hybridoma, have been established, and hybridomas secreting anti-tetanus
      toxoid and anti-HBsAg human monoclonal antibodies (MoAbs), both having a
      neutralizing activity have been obtained. Cell-line improvement was shown to be
      an efficient method for improving the productivity in a cell culture process. Two
      kinds of serum-free media, GFS (a serum substitute)-containing media and
      polyethylene glycol (PEG)-containing media, have been established to produce
      human MoAbs. m.h-h Heterohybridomas could be cultivated for a long period by
      perfusion culture in an agitation vessel, but h-h hybridomas could not. We found
      that h-h hybridomas show growth-associated antibody production kinetics and
      established two kinds of long-term cultivation systems: continuous perfusion
      culture and semicontinuous immobilized perfusion culture. We also scaled up batch
      culture and short-term perfusion culture to 200-L and 50-L fermentors,
      respectively. Processes for large-scale purification from the culture
      supernatants of both GFS- and PEG-containing serum-free media have also been
      developed.

PMID- 22359047
TI  - "Differentiation Induction" culture of human leukemic myeloid cells stimulates
      high production of macrophage differentiation inducing factor.
AB  - A suitable procedure for the production of human monokines was defined as
      'differentiation-induction' culture. Human monocytic leukemia THP-1 cells were
      well-differentiated from nonfunctional promonocytes into macrophage-like cells by
      the induction with a combination of mezerein, retinoic acid, and aMycoplasma
      fermentans extract. The differentiated THP-1 cells secreted a high amount of
      macrophage differentiation-inducing factor (DIF) activity and concomitantly
      produced other known monokines, such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1alpha (IL-1alpha) and interleukin-1beta (IL-1beta), into the medium.
      These results suggest that other novel human monokines may also be found in the
      conditioned medium of THP-1 cells induced by the 'differentiation-induction'
      culture conditions defined in this study. Macrophage DIF was purified to
      homogeneity and NH(2)-terminal amino acid sequence analysis revealed that
      macrophage DIF is very similar or identical to human leukemia inhibitory factor
      (LIF). The cDNA encoding human LIF was isolated using the polymerase chain
      reaction, and a clone producing 3.7 MUg/10(6) cells day recombinant LIF was
      selected from Chinese hamster ovary (CHO) cells which were transfected with the
      LIF cDNA. The recombinant LIF production in CHO cells was quantified using MTT
      reduction assay with M1 cells.

PMID- 22359048
TI  - Serum-free cultivation of anchorage-dependent cells on microcarrier: Effective
      production of human macrophage colony-stimulating factor.
AB  - For the purpose of establishing a large scale production process of biologically
      active substances by cultivation of anchorage-dependent mammalian cells, basic
      studies were carried out on the following items; establishment of a new cell line
      and derivation of high productivity; construction of optimal serum-free medium;
      optimization of cultivation method using microcarrier in serum-free medium; and
      establishment of purification process. The cell line, TRC-29SF, used in this
      study was newly established from human renal carcinoma with a function of
      producing macrophage colony-stimulating factor constitutively. Improvement of M
      CSF productivity upon TRC-29SF cell line was performed by M-CSF gene
      amplification with dhfr-MTX system and by truncation of membrane-binding amino
      acid sequence by recombinant DNA technique. Two kinds of serum-free media, IPEG
      85 and IREG-89, were formulated for the growth of TRC-29SF cell and its
      transformant, respectively. A new cell-adhesion method which permits homogeneous
      attachment to microcarrier in short term was developed by equalising the
      sedimentation velocity between cells and microcarrier by addition of 7% Ficoll
      into the medium. High cell density perfusion culture of TRC-29SF cells was
      achieved by microcarrier method using IPEG-85 medium, and final cell density
      reached over 10(7) cells/ml. Based on the results obtained, long-term perfusion
      cultures were performed using Mn10-5 and Mn10-5/R600 cell lines, which were
      created by M-CSF gene transfection and amplification. We found that the
      productivity of M-CSF per cell began to decrease from the end of logarithmic
      growth phase. Long-term cultivation with high productivity was accomplished by
      perfusing medium containing 2 mM sodium butyrate. Purification process for M1-CSF
      from the culture supernatant of transformed cell line was also established.

PMID- 22359049
TI  - RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts.
AB  - The significant biological role of RNA has further highlighted the need for
      improving the accuracy, efficiency and the reach of methods for investigating RNA
      structure and function. Nuclear magnetic resonance (NMR) spectroscopy is vital to
      furthering the goals of RNA structural biology because of its distinctive
      capabilities. However, the dispersion pattern in the NMR spectra of RNA makes
      automated resonance assignment, a key step in NMR investigation of biomolecules,
      remarkably challenging. Herein we present RNA Probabilistic Assignment of Imino
      Resonance Shifts (RNA-PAIRS), a method for the automated assignment of RNA imino
      resonances with synchronized verification and correction of predicted secondary
      structure. RNA-PAIRS represents an advance in modeling the assignment paradigm
      because it seeds the probabilistic network for assignment with experimental NMR
      data, and predicted RNA secondary structure, simultaneously and from the start.
      Subsequently, RNA-PAIRS sets in motion a dynamic network that reverberates
      between predictions and experimental evidence in order to reconcile and rectify
      resonance assignments and secondary structure information. The procedure is
      halted when assignments and base-parings are deemed to be most consistent with
      observed crosspeaks. The current implementation of RNA-PAIRS uses an initial peak
      list derived from proton-nitrogen heteronuclear multiple quantum correlation
      ((1)H-(15)N 2D HMQC) and proton-proton nuclear Overhauser enhancement
      spectroscopy ((1)H-(1)H 2D NOESY) experiments. We have evaluated the performance
      of RNA-PAIRS by using it to analyze NMR datasets from 26 previously studied RNAs,
      including a 111-nucleotide complex. For moderately sized RNA molecules, and over
      a range of comparatively complex structural motifs, the average assignment
      accuracy exceeds 90%, while the average base pair prediction accuracy exceeded
      93%. RNA-PAIRS yielded accurate assignments and base pairings consistent with
      imino resonances for a majority of the NMR resonances, even when the initial
      predictions are only modestly accurate. RNA-PAIRS is available as a public web
      server at http://pine.nmrfam.wisc.edu/RNA/.

PMID- 22359050
TI  - Impact of type of thrombolytic agent on in-hospital outcomes in ST-segment
      elevation myocardial infarction patients in the Middle East.
AB  - Little is known about the impact of thrombolytic agents on in-hospital outcomes
      in the Middle East. The objective of this study was to evaluate the impact of
      thrombolytic agents on in-hospital outcomes in ST-segment elevation myocardial
      infarction (STEMI) patients in six Middle Eastern countries. Gulf Registry of
      Acute Coronary Events was a prospective, multinational, multicentre,
      observational survey of consecutive acute coronary syndrome patients admitted to
      65 hospitals in 2006 and 2007. Out of 1,765 STEMI patients admitted to hospitals
      within 12 h of symptoms onset, 25, 43, and 30% were treated with streptokinase,
      reteplase, and tenecteplase, respectively. Median age of the study cohort was 50
      (45-59) years and majority were males (89%). The overall median symptom onset-to
      presentation and median door-to-needle times were 130 min (65-240) and 45 min (30
      75), respectively. Streptokinase patients had worse GRACE risk scores compared to
      patients who received fibrin specific thrombolytics. Academic hospitals and
      cardiologists as admitting physicians were associated with the use of fibrin
      specific thrombolytics. After significant covariate adjustment, both reteplase
      [odds ratio (OR), 0.38; 95% CI: 0.18-0.79; P = 0.009] and tenecteplase (OR, 0.30;
      95% CI: 0.12-0.77; P = 0.012) were associated with lower all-cause in-hospital
      mortality compared with streptokinase. No significant differences in other in
      hospital outcomes were noted between the thrombolytic agents. In conclusion, in
      light of the study's limitations, fibrin specific agents, reteplase and
      tenecteplase, were associated with lower all-cause in-hospital mortality compared
      to the non-specific fibrin agent, streptokinase. However, the type of
      thrombolytic agent used did not influence other in-hospital outcomes.

PMID- 22359051
TI  - Down-regulation of CRMP-1 in patients with epilepsy and a rat model.
AB  - The Collapsin Response Mediator Protein-1 (CRMP-1) is a brain specific protein
      identified as a signaling molecule of Semaphorin-3A and act as axon repellent
      guidance factor in nervous system. Recent studies indicated that axon guidance
      molecules may play a role in synaptic reorganization in the adult brain and
      thereby promote epileptogenesis. This study aimed to investigate expression
      pattern of CRMP-1 in epileptogenesis. Using double immunofluorescence labeling,
      immunohistochemistry and western blot analysis, we looked into the CRMP-1
      expression in temporal neocortex from patients with temporal lobe epilepsy (TLE)
      and histological normal temporal neocortex from the controls. We also studied the
      expression pattern of CRMP-1 in hippocampus and adjacent cortex of a TLE rat
      model on 6, 24, 72 h, 1, 2 weeks, 1 month, and 2 months post-seizure, and from
      control rats. CRMP-1 was mainly expressed in the neuronal cytoplasm in the
      temporal lobe of intractable TLE patients, which was co-expressed with -2. CRMP-1
      expression was downregulated in temporal neocortical of TLE patients. In
      addition, in pilocarpine-induced animal model of epilepsy, CRMP-1 dynamically
      decreased in a range of 2 months. Thus, our results indicate that CRMP-1 may be
      involved in the development of TLE.

PMID- 22359052
TI  - Pannexin1-mediated ATP release provides signal transmission between Neuro2A
      cells.
AB  - Pannexin1 (Panx1), a protein related to the gap junction proteins of
      invertebrates, forms nonjunctional channels that open upon depolarization and in
      response to mechanical stretch and purinergic receptor stimulation. Importantly,
      ATP can be released through Panx1 channels, providing a possible role for these
      channels in non-vesicular signal transmission. In this study we expressed
      exogenous human and mouse Panx1 in the gap junction deficient Neuro2A
      neuroblastoma cell line and explored the contribution of Panx1 channels to cell
      cell communication as sites of ATP release. Electrophysiological (patch clamp)
      recordings from Panx1 transfected Neuro2A cells revealed membrane conductance
      that increased beyond 0 mV when applying voltage ramps from -60 to +100 mV;
      threshold was correlated with extracellular K+, so that at 10 mM K+, channels
      began to open at -30 mV. Evaluation of cell-cell communication using dual whole
      cell recordings from cell pairs revealed that activation of Panx1 current in one
      cell of the pair induced an inward current in the second cell after a latency of
      10-20 s. This paracrine response was amplified by an ATPase inhibitor (ARL67156,
      100 MUM) and was blocked by the ATP-degrading enzyme apyrase (6.7 U/ml), by the
      P2 receptor antagonist suramin (50 MUM) and by the Panx1 channel blocker
      carbenoxolone. These results provide additional evidence that ATP release through
      Panx1 channels can mediate nonsynaptic bidirectional intercellular communication.
      Furthermore, current potentiation by elevated K+ provides a mechanism for
      enhancement of ATP release under pathological conditions.

PMID- 22359053
TI  - High-glucose and S100B stimulate glutamate uptake in C6 glioma cells.
AB  - Diabetes mellitus is a disease associated with several changes in the central
      nervous system, including oxidative stress and abnormal glutamatergic
      neurotransmission, and the astrocytes play an essential role in these
      alterations. In vitro studies of astroglial function have been performed using
      cultures of primary astrocytes or C6 glioma cells. Herein, we investigated
      glutamate uptake, glutamine synthetase and S100B secretion in C6 glioma cells
      cultured in a high-glucose environment, as well as some parameters of oxidative
      stress and damage. C6 glioma cells, cultured in 12 mM glucose medium, exhibited
      signals of oxidative and nitrosative stress similar to those found in diabetes
      mellitus and other models of diabetic disease (decrease in glutathione, elevated
      NO, DNA damage). Interestingly, we found an increase in glutamate uptake and
      S100B secretion, and a decrease in glutamine synthetase, which might be linked to
      the altered glutamatergic communication in diabetes mellitus. Moreover, glutamate
      uptake in C6 glioma cells, like primary astrocytes, was stimulated by
      extracellular S100B. Aminoguanidine partially prevented the glial alterations
      induced by the 12 mM glucose medium. Together, these data emphasize the relevance
      of astroglia in diabetes mellitus, as well as the importance of glial parameters
      in the evaluation of diabetic disease progression and treatment.

PMID- 22359054
TI  - The acetylcholinesterase inhibitors competitively inhibited an acetyl L-carnitine
      transport through the blood-brain barrier.
AB  - We investigated the interaction of acetylcholinesterase (AChE) inhibitors with
      acetyl-L-carnitine (ALCAR) transporter at the blood-brain barrier (BBB). ALCAR
      uptake by conditionally immortalized rat brain capillary endothelial cell lines
      (TR-BBB cells), as an in vitro model of BBB, were characterized by cellular
      uptake study using [(3)H]ALCAR. In vivo brain uptake of [(3)H]ALCAR was
      determined by brain uptake index after carotid artery injection in rats. In
      results, the transport properties for [(3)H]ALCAR by TR-BBB cell were consistent
      with those of ALCAR transport by the organic cation/carnitine transporter 2
      (OCTN2). Also, OCTN2 was confirmed to be expressed in the cells. The uptake of
      [(3)H]ALCAR by TR-BBB cells was inhibited by AChE inhibitors such as donepezil,
      tacrine, galantamine and rivastigmine, which IC(50) values are 45.3, 74.0, 459
      and 800 MUM, respectively. Especially, donepezil and galantamine inhibited the
      uptake of [(3)H]ALCAR competitively, but tacrine and rivastigmine inhibited
      noncompetitively. Furthermore, [(3)H]ALCAR uptake by the rat brain was found to
      be significantly decreased by quinidine, donepezil and galantamine. Our results
      suggest that transport of AChE inhibitors such as donepezil and galantamine
      through the BBB is at least partly mediated by OCTN2 which is involved in
      transport of ALCAR.

PMID- 22359055
TI  - Plasma membrane-associated glycohydrolases activation by extracellular
      acidification due to proton exchangers.
AB  - In this paper, we show that the pH optimum for the plasma membrane (PM)
      associated activity of four glycohydrolases (conduritol B epoxide sensitive beta
      glucosidase, beta-glucosidase GBA2, beta-hexosaminidase and beta-galactosidase)
      measured on intact cells is acidic. Moreover, we show that drugs able to modify
      the efflux of protons across the PM, thus locally affecting the extracellular
      proton concentration close to the PM, are able to modulate the activities of
      these enzymes. These data strongly suggest that pH-dependent modulation of PM
      associated glycohydrolases activities could be an effective way to locally
      modulate the cell surface glycoconjugate composition.

PMID- 22359057
TI  - Optimization of the production of triabin, a novel thrombin inhibitor, in High
      FiveTM insect cells infected with a recombinant baculovirus.
AB  - The isolation of a new type of thrombin inhibitor, called triabin, from the
      saliva of the hematophagous bug Triatoma pallidipennis, has recently been
      described. In the in vitro platelet aggregation inhibition assay triabin has a
      similar potency as the thrombin inhibitor hirudin now in phase III clinical
      trials. However, in another in vitro assay using a low molecular weight substrate
      for thrombin, triabin does not inhibit thrombin completely even at 6 fold higher
      molar doses in comparison with hirudin. This means that triabin has a novel mode
      of action towards thrombin making triabin into an interesting candidate as a
      therapeutic agent. Recently it has been shown that a recombinant baculovirus can
      be efficiently used for the triabin production in insect cells and that the
      yields in adherent cultures of High FiveTM cells (approx. 20 mg l-1) were about 7
      fold higher than in adherent cultures of Sf9 cells (approx. 3 mg l- 1). To
      optimize the triabin yield from the baculovirus/insect cell expression system,
      experiments were performed with suspension adapted cultures of High FiveTM cells
      to investigate the effects of the state of the host cell, of the multiplicity of
      infection, of the cell density at the time of infection and of supplementation of
      the medium with nutrients and oxygen. Triabin yields of up to 200 mg l-1, as
      determined by an activity assay, could finally be obtained here.

PMID- 22359056
TI  - NR2B-containing NMDA receptors expression and their relationship to apoptosis in
      hippocampus of Alzheimer's disease-like rats.
AB  - Although studies have shown that excitotoxicity mediated by N-methyl-D-aspartate
      receptors (NMDARs, NR) plays a prominent role in Alzheimer's disease (AD), the
      precise expression patterns of NMDARs and their relationship to apoptosis in AD
      have not been clearly established. In this study, we used Abeta (Abeta) 1-40 and
      AlCl(3) to establish AD rat model. The behavioral changes were detected by morris
      water maze and step-down test. The hippocampal amyloid deposition and
      pathological changes were determined by congo red and hematoxylin-eosin staining.
      Immunohistochemistry was used to detect expression of NR1, NR2A and NR2B, and
      TUNEL staining was used to detect apoptosis. Results showed that water maze
      testing escape latency of AD-like rats was prolonged significantly. Reaction
      time, basal number of errors, and number of errors of step-down test were
      increased significantly; latency period of step-down test was shortened
      significantly in AD-like rats. Amyloid substance deposition and obvious damage
      changes could be seen in hippocampus of AD-like rats. These results suggested
      that AD rat model could be successfully established by Abeta1-40 and AlCl(3).
      Results also showed that expression of NR1 and NR2B were significantly increased,
      but expression of NR2A had no significant change, in AD-like rat hippocampus.
      Meanwhile, apoptotic cells were significantly increased in AD-like rat
      hippocampus, especially in CA1 subfield and followed by dentate gyrus and CA3
      subfield. These results implied that NR2B-, not NR2A-, containing NMDARs showed
      pathological high expression in AD-like rat hippocampus. This pathological high
      expression with apoptosis and selective vulnerability of hippocampus might be
      exist a specific relationship.

PMID- 22359058
TI  - Quantitative analysis of transcription and translation in gene amplified Chinese
      hamster ovary cells on the basis of a kinetic model.
AB  - The elevation of expression levels for secreted glycoproteins by gene
      amplification in mammalian cells shows a saturation behavior at high levels of
      gene amplification. At high expression levels a drop in the secretion efficiency
      for the recombinant protein occurs (Schroder and Friedl, 1997), coinciding with
      the appearance of misfolded protein in the cell. In this communication we
      investigated whether additional limitations exist at the levels of transcription
      and translation. Four Chinese hamster ovary (CHO) cell lines expressing different
      amounts of human antithrombin III (ATIII) were used as a model system. A tenfold
      increase in the ATIII cDNA copy number from the lowest to the highest producing
      cell line coincided with a 38-fold increase in ATIII mRNA levels, and an 80-fold
      increase in the amount of intracellular ATIII levels. The data was analyzed using
      a simple kinetic model. The following conclusions were derived: I. The
      transcriptional activity for the recombinant protein is not saturated. II.
      Translation itself is not saturated either, but may be downregulated as secretion
      efficiency drops. III. Two explanations for the previously reported drop in
      secretion efficiency for the recombinant protein with increasing expression level
      are possible: A. Protein degradation is an alternative fate for translated ATIII
      and the fraction of ATIII degraded after translation increases as expression
      level is increased. B. Translation is downregulated as the secretory apparatus
      becomes exhausted to maintain cell viability.

PMID- 22359059
TI  - DNA content analysis of insect cell lines by flow cytometry.
AB  - The DNA content of insect cell lines (6 lepidoptera, 1 coleoptera and 1 diptera)
      was determined by flow cytometry. The DNA profiles of the 8 cell lines tested
      were different. They were characterized by the presence of several peaks (2 to 7)
      corresponding to different ploidy levels, by differences in the fluorescence
      intensity of each peak and by the proportion of cells in each peak. Two cell
      lines (Cf124 and BmN) were constituted of 2 distinct populations of cells. The
      DNA profiles of the cell lines were stable among the passages and during the
      length of time culture. This technique was demonstrated to be useful for the
      detection of mixed cell lines and nucleopolyhedrovirus cell infection, using
      Autographa californica MNPV. The flow cytometry gives interesting results on the
      cell cycle and the ploidy level; it appears as a good tool for insect cell lines
      characterization.

PMID- 22359060
TI  - Formation of monoclonal antibody against a major ginseng component, ginsenoside
      Rb1 and its characterization.
AB  - The ratio of hapten and bovine serum albumin in an antigen conjugate was
      determined by matrix-assisted laser desorption/ionization mass spectrometry. A
      hybridoma secreting monoclonal antibody against ginsenoside Rb1 was produced by
      fusing splenocytes immunized with a ginsenoside Rb1- bovine serum albumin
      conjugate with HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. A very
      small cross-reaction appeared with ginsenoside Rc and ginsenoside Rd. The full
      measuring range of the assay extends from 20 ngml-1 to 400 ngml-1 of ginsenoside
      Rb1.

PMID- 22359061
TI  - Improvement of a cytokine (TNF-alpha) bioassay by serum-free target cell (WEHI
      164) cultivation.
AB  - The elaboration of a sensitive bioassay for assessment of tumour necrosis factor
      alpha (TNF-alpha) in a defined medium is described. The assay is based on the
      cytotoxic effect of TNF-alpha on a target cell line, the murine fibrosarcoma WEHI
      164 clone 13. Cytotoxicity was assessed by detecting the rate of tetrazolium salt
      reduction employing a spectrophotometer (ELISA-reader). A similar bioassay was
      used previously to assess TNF-alpha, though this was dependent on cell growth in
      a medium containing serum. By employing a synthetic serum replacement, the WEHI
      cells were adapted to growth in a defined medium which allowed both the
      propagation of the cell line and the assay to be performed under completely
      defined conditions. Thus, factors in serum that may influence the TNF-alpha
      assessment, such as growth factors, cytokines, soluble cytokine-receptors and
      macroglobulin, were avoided. The only protein required in this bioassay was
      insulin, while albumin was added as a carrier protein and to protect the cytokine
      against loss of biological activity during multiple freeze and thaw cycles. The
      present assay was optimised to achieve a high sensitivity and, by testing
      endogenous TNF-alpha originating from the macrophage-like cell line RAW in both
      the serum-free and serum-based assay, we found the highest sensitivity in the
      assay based on defined medium. The LC50 of recombinant mouse and human TNF-alpha
      were in the serum-free and serum-based assays considered to be 25 and 50 pg mL-1,
      respectively. The demonstration of a culture condition that enables long-term
      cultivation of target cells and a bioassay in a completely defined medium is in
      our opinion a substantial contribution to more reliable cytokine assessment.

PMID- 22359062
TI  - A microcarrier-based cell culture process for the production of a bovine
      respiratory syncytial virus vaccine.
AB  - Veterinary viral vaccines generally comprise either attenuated or chemically
      inactivated viruses which have been propagated on mammalian cell substrates or
      specific pathogen free (SPF) eggs. New generation vaccines include chemically
      inactivated virally-infected whole cell vaccines. The NM57 cell line is a bovine
      nasal turbinate persistently infected (non-lytic infection) with a strain of the
      respiratory syncytial virus (RSV). The potential of microcarrier technology for
      the cultivation in bioreactors of this anchorage dependent cell line for RSV
      vaccine production has been investigated. Both Cytodex 3 and Cultispher S
      microcarriers proved most suitable from a selection of microcarriers as growth
      substrates for this NM57 cell line. Maximum cell densities of 4.12*105 cells ml
      1and 5.52*105 cells ml-1 respectively were obtained using Cytodex 3 (3 g l-1) and
      and Cultispher S (1 g l-1) in 5 l bioreactor cultures. The fact that cell growth
      was less sensitive to agitation rate when cultured on Cultispher S microcarriers,
      and that cells were efficiently harvested from this microcarrier by an enzymatic
      method, suggested Cultispher S is suitable for further evaluation at larger
      bioreactor scales (>5 l) than that described here.

PMID- 22359063
TI  - Cell growth and protein formation on various microcarriers.
AB  - A large number of microcarriers are commercially available. The capability of
      cells to successfully proliferate on microcarriers varies with cell lines and
      media. Choosing the right microcarrier for a particular cell line is more than a
      choice of a microcarrier. It is part of an integrated process design. A detailed
      picture of cell growth and product formation will not only be essential in
      identifying the kind of microcarrier, but also in determining other parts of the
      process, such as operation mode and media. Our initial screening on thirteen
      microcarriers showed that cultures on some microcarriers reached a low cell
      density but high cell-specific productivity, and high density microcarrier
      cultures have a low specific productivity. The result is a similar product output
      per unit volume and time for these two types of cultures. An ideal culture system
      shall have increased volumetric productivity at elevated cell density. This
      requires the process goal to be incorporated as early as cell line construction
      and screening. A high output process can then be realized through high density
      culture.

PMID- 22359064
TI  - Exploration of respiratory chain of Nocardia asteroides: purification of
      succinate quinone oxidoreductase.
AB  - Nocardia asteroides is a pathogenic bacterium that causes severe pulmonary
      infections and plays a vital role in HIV development. Its electron transport
      chain containing cytochromes as electron carriers is still undiscovered.
      Information regarding cytochromes is important during drug synthesis based on
      cytochrome inhibitions. In this study we explored the electron transport of N.
      asteroides. Spectroscopic analysis of cytoplasm and membranes isolated from N.
      asteroides indicates the presence of soluble cytochrome-c, complex-II and the
      modified a(1)c(1) complex as the terminal oxidase. The molecular weight of the
      respiratory complex-II isolated and purified from the given bacterium was 103 kDa
      and was composed of three subunits, of 14, 26 and 63 kDa. Complex-II showed
      symmetrical alpha-absorption peaks at 561 nm in the reduced state. Spectral
      analysis revealed the presence of only one heme b molecule (14-kDa subunit) in
      complex-II, which was confirmed by heme staining. Heme b content was found to be
      9.5 nmol/mg in complex-II. The electron transport chain of N. asteroides showed
      the presence of soluble cytochrome-c, cytochrome-a(1)c(1) and cytochrome-b.

PMID- 22359065
TI  - Hyperpolarization of the membrane potential in cardiomyocyte tissue slices by the
      synchronization modulation electric field.
AB  - Our previous studies have shown that a specially designed, so-called
      synchronization modulation electric field can entrain active transporter Na/K
      pumps in the cell membrane. This approach was previously developed in a study of
      single cells using a voltage clamp to monitor the pump currents. We are now
      expanding our study from isolated single cells to aggregated cells in a 3
      dimensional cell matrix, through the use of a tissue slice from the rat heart.
      The slice is about 150 MUm in thickness, meaning the slices contain many cell
      layers, resulting in a simplified 3-dimensional system. A fluorescent probe was
      used to identify the membrane potential and the ionic concentration gradients
      across the cell membrane. In spite of intrinsic cell-to-cell interactions and the
      difficulty in stimulating cell aggregation in the tissue slice, the oscillating
      electric field increased the intracellular fluorescent intensity, indicating
      elevation of the cell ionic concentration and hyperpolarization of the cell
      membrane. Blockage of these changes by ouabain confirmed that the results are
      directly related to Na/K pumps. These results along with the backward modulation
      indicate that the synchronization modulation electric field can influence the
      Na/K pumps in tissue cells of a 3-dimensional matrix and therefore hyperpolarize
      the cell membrane.

PMID- 22359066
TI  - Promiscuous enantioselective (-)-gamma-lactamase activity in the Pseudomonas
      fluorescens esterase I.
AB  - A promiscuous but very enantioselective (-)-gamma-lactamase activity in the
      kinetic resolution of the Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) was
      detected in the Pseudomonas fluorescens esterase I (PFEI). The lactamase activity
      was increased 200-fold by the introduction of a point mutation and resulted as
      enantioselective as the Microbacterium sp. enzyme used industrially in this
      resolution. The structural and mechanistic determinants for the catalytic
      promiscuity and enantioselectivity were identified by molecular modeling, setting
      a ground stone to engineer further amidase-related activities from this esterase.

PMID- 22359068
TI  - Migraine and allergy: a review and clinical update.
AB  - Migraine and allergy are both common diseases. Many patients suffer from both,
      and the vast majority of patients with "sinus headache" complaints are found to
      have migraine, making migraine identification important to allergists. This
      review addresses the possibility that allergy and migraine are comorbid
      conditions, focusing on epidemiology, shared biochemical pathways, and underlying
      mechanisms. Therapeutic implications of this possible relationship have been the
      subject of several recent studies, making a review of this association timely and
      prudent.

PMID- 22359067
TI  - Clinical overview of cutaneous features in hypereosinophilic syndrome.
AB  - The hypereosinophilic syndromes (HES) are a heterogeneous group of disorders
      defined as persistent and marked blood eosinophilia of unknown origin with
      systemic organ involvement. HES is a potentially severe multisystem disease
      associated with considerable morbidity. Skin involvement and cutaneous findings
      frequently can be seen in those patients. Skin symptoms consist of angioedema;
      unusual urticarial lesions; and eczematous, therapy-resistant, pruriginous
      papules and nodules. They may be the only obvious clinical symptoms. Cutaneous
      features can give an important hint to the diagnosis of this rare and often
      severe illness. Based on advances in molecular and genetic diagnostic techniques
      and on increasing experience with characteristic clinical features and prognostic
      markers, therapy has changed radically. Current therapies include
      corticosteroids, hydroxyurea, interferon-alpha, the tyrosine kinase inhibitor
      imatinib mesylate, and (in progress) the monoclonal anti-interleukin-5
      antibodies. This article provides an overview of current concepts of disease
      classification, different skin findings, and therapy for HES.

PMID- 22359069
TI  - Application of passive sampling on assessment of concentration distribution and
      health risk of volatile organic compounds at a high-tech science park.
AB  - The objectives of this study are to investigate the volatile organic compound
      (VOC) distribution using passive samplers and to assess the resulting health
      risks in a high-tech science industrial park. With the advantages of passive
      sampling techniques, long-term and wide-area samples are collected. The results
      show TVOC concentrations in summer, fall, winter, and spring are 7.14 +/- 5.66
      ppb, 18.17 +/- 5.81 ppb, 10.30 +/- 3.54 ppb, and 14.56 +/- 4.53 ppb,
      respectively; those on weekdays and weekends are 14.36 +/- 6.80 ppb and 9.87 +/-
      4.86 ppb, respectively; and those in industrial and residential zones are 12.97
      +/- 0.39 ppb and 11.13 +/- 0.68 ppb, respectively. Based on concentration
      variations, and benzene, toluene, ethylbenzene, and xylene ratios, we can resolve
      the source origins. Health risks are assessed based on the resulting
      concentrations. In the case of non-cancer chronic effects, long-term exposure to
      these concentrations does not support there is a risk of adverse health effects.
      However, potential cancer risks of exposure to these concentrations may occur,
      especially to carbon tetrachloride and benzene. By applying this study's
      procedures, information on VOC concentration distribution, source identification,
      and health assessment can be obtained and they are applicable to similar studies.

PMID- 22359070
TI  - Differential consequences of protein kinase C activation during early and late
      hepatic ischemic preconditioning.
AB  - Activation of protein kinase C (PKC) has been implicated in the protection of
      ischemic preconditioning (IPC), but the exact role of PKC in early and late
      hepatic IPC is still unclear. The present study was conducted in order to
      investigate the differential role of PKC during early and late hepatic IPC. Rats
      were subjected to 90 min of partial hepatic ischemia followed by 3 (early IPC)
      and 24 h (late IPC) of reperfusion. IPC was induced by 10 min of ischemia
      following 10 min of reperfusion prior to sustained ischemia, and chelerythrine, a
      PKC inhibitor, was injected 10 min before IPC (5 mg/kg, i.v.). Chelerythrine
      abrogated the protection of early IPC, as indicated by increased serum
      aminotransferase activities and decreased hepatic glutathione content. While the
      IPC-treated group showed a few apoptotic cell deaths during both phases,
      chelerythrine attenuated these changes only at late IPC and limited IPC-induced
      inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1)
      overexpression. Membrane translocation of PKC-delta and -epsilon during IPC was
      blocked by chelerythrine. Our results suggest that PKC might play a differential
      role in early and late IPC; activation of PKC-delta and -epsilon prevents
      necrosis in early IPC through preservation of redox state and prevents apoptosis
      in late IPC with iNOS and HO-1 induction. Therefore, PKC represents a promising
      target for hepatocyte tolerance to ischemic injury, and understanding the
      differential role of PKC in early and late IPC is important for clinical
      application of IPC.

PMID- 22359073
TI  - Animal cells in culture are microorganisms.
AB  - Pick up any textbook with 'Microbiology' in the title and observe the scant to
      nonexistent treatment of animal cells in culture. Viruses do not suffer from such
      an exclusion. Chapters abound regaling the molecular niceties of the complex
      dances their components undergo while infecting bacteria or animal cells in
      culture. Indeed, it is normally in the latter sense only that any recognition is
      given to the existence of animal cells in culture. Such views pervade even the
      minds of those who initiate and direct activities of societies whoseraison d'etre
      is the growth and exploitation of animal cells in culture. The author of this
      editorial was appointed to a Chair in Microbiology at the University of Surrey in
      1983 and has worked on the growth and use of animal cells in culture continuously
      since 1970; he, therefore, had to reconcile his position in the university with
      his chosen calling. In this he was helped by undergraduates too numerous to
      mention who struggled mightily with essays which asked the question; are animal
      cells in culture microorganisms? What follows is a digest of their efforts and
      the views of the author.

PMID- 22359071
TI  - Inflammation, atherosclerosis, and psoriasis.
AB  - Increasing evidence supports an important role for inflammation in all phases of
      atherosclerosis, from initiation of the fatty streak to final culmination in
      acute coronary syndromes. Numerous inflammatory biomarkers including cell
      adhesion molecules, cytokines, chemokines, and acute-phase reactants such as
      fibrinogen, serum amyloid A, and C-reactive protein (CRP) have been shown to
      predict cardiovascular (CVD) events. Several prospective studies have shown a
      consistent and robust relationship between levels of high-sensitivity CRP and the
      risk of future CVD events. Toll-like receptors are pattern recognition receptors
      and members of the innate immune system that contribute to inflammation and
      appear to play key roles in atherosclerosis. Lipoprotein-associated phospholipase
      A2 may also be an independent CVD risk factor. Psoriasis has been associated with
      an increasing risk for atherosclerosis, including coronary artery disease and
      stroke. Patients with psoriasis have a 5-year shorter life expectancy, most
      frequently due to CVD. Psoriasis is associated with a chronic inflammatory state
      and with elevated levels of CRP and other inflammatory cytokines and these may
      play a causative role in the increased risk of psoriatic patients for CVD.
      Patients with psoriasis may represent an emerging risk population and patients
      with moderate to severe psoriasis should be screened and aggressively treated for
      CVD risk factors.

PMID- 22359074
TI  - Applications of cell culture for the improvement of human health.
AB  - Current applications of Cell Culture Engineering which have a major beneficial
      impact for the improvement of human health range from a great variety of vaccines
      (examples include measles, mumps, rubella, polio, and Hepatitis A) made using
      this technology to a whole new range of therapeutic proteins dependent for their
      expression on animal cell culture hosts (examples include EPO, TPA and gamma
      interferon). Novel applications "in the pipeline" include cell therapy products
      and gene therapy products.

PMID- 22359072
TI  - A cutting edge overview: psoriatic disease.
AB  - Psoriasis is a lifelong skin disease, affecting about 2% of the global
      population. Generalized involvement of the body (erythroderma), extensive
      pustular lesions, and an associated arthritis known as psoriatic arthritis (PsA)
      are severe complications of psoriasis. Genetic, immunologic, and environmental
      factors contribute to its pathogenesis. A complete understanding of the
      pathogenesis of psoriasis and psoriatic arthritis is lacking. Cytokines,
      chemokines, adhesion molecules, growth factors like NGF, neuropeptides, and T
      cell receptors all act in an integrated way to evolve into unique inflammatory
      and proliferative processes typical of psoriasis and PsA. Management of psoriasis
      requires exemplary skin care along with careful monitoring of arrays of
      comorbidities which includes arthritis and coronary artery disease. In many ways,
      psoriasis can be considered a model autoimmune disease. This statement itself is
      ironic considering that it was not recognized as immune mediated until relatively
      recently. Fortunately, the immunobiology has made enormous strides and there are
      now excellent therapeutic options for patients. In this thematic review, we have
      attempted to provide summaries of not only basic science and clinical research,
      but also an overview of future research directions.

PMID- 22359075
TI  - Chronic treatment with the phosphodiesterase type 5 inhibitors sildenafil and
      tadalafil display anxiolytic effects in Flinders Sensitive Line rats.
AB  - There are conflicting results from behavioural studies regarding whether the
      activation or inhibition of the cGMP-nitric oxide (NO) pathway induces anxiolytic
      like behaviour. Sildenafil, an inhibitor of cGMP-selective phosphodiesterase-5,
      increases anxiety acutely, but previous evidence suggests that its chronic
      administration may be anxiolytic, and could involve a cholinergic interaction. We
      used the Flinders Sensitive Line (FSL) rat, a genetic model of depression that
      presents with increased anxiety- and depression-like behaviour, to investigate
      the action of chronic treatment with the PDE5 inhibitors sildenafil or tadalafil,
      with/without atropine on social interaction behaviour, a correlate for anxiety.
      Fluoxetine was used as positive control, with validation performed using Flinders
      Resistant Line (FRL) rats. In order to relate behavioural changes to brain
      penetration, we determined the concentration of sildenafil in cortex and
      hippocampus of rats following the schedule above using LC-MS/MS. FSL rats
      displayed significantly reduced social interactive behaviour than FRL rats, while
      sildenafil, tadalafil, and fluoxetine significantly reversed these deficits.
      Atropine did not exert effects on social interactive behaviour, nor did it
      modulate the effects of sildenafil or tadalafil. Sildenafil was present in cortex
      and hippocampus regions in lower nanomolar concentrations after chronic
      treatment, in agreement with the binding to PDE5 required for pharmacological
      effects. This study emphasizes the complicated regulation of anxiety by the cGMP
      NO system, and provides supporting evidence for an anxiolytic action after the
      chronic activation of this pathway. As far as we know this is also the first
      report to formally demonstrate that sildenafil effectively crosses the blood
      brain barrier to elicit central effects.

PMID- 22359076
TI  - Stem cell therapy in treatment of different diseases.
AB  - Stem cells are undifferentiated cells with the ability of proliferation,
      regeneration, conversion to differentiated cells and producing various tissues.
      Stem cells are divided into two categories of embryonic and adult. In another
      categorization stem cells are divided to Totipotent, Multipotent and Unipotent
      cells.So far usage of stem cells in treatment of various blood diseases has been
      studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple
      myeloma and cycle cell anemia). In this paper the goal is evaluation of cell
      therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis,
      Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced
      Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular
      Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds,
      Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be
      mentioned that some disease that are the target of cell therapy are discussed in
      this article.

PMID- 22359077
TI  - Interferon-beta in pediatric multiple sclerosis patients: safety in short-term
      prescription.
AB  - None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS)
      patients have been officially approved for the pediatric patients and are
      currently used off-label in this population. In this study, we evaluated the
      effectiveness and tolerability of intramuscular interferon beta1-a (Avonex((r)))
      and subcutaneously injected interferon beta1-b (Betaferon((r))) in children with
      definite relapsing-remitting MS (RRMS). Thirteen patients aged younger than 16,
      who were recently diagnosed with definite RRMS according to the McDonald's
      criteria, were enrolled in this study. Six patients were treated with Avonex((r))
      30 MUg, intramuscularly every week, and seven patients were treated with
      Betaferon((r)) 250 MUg, subcutaneously every other day. All patients were treated
      with adult doses; initially interferon-beta was prescribed with half dose, and it
      was increased to full adult dose steadily. Eleven girls and two boys, mean (SD)
      age of 14.7 (1.9) years, were studied. Following nine months of using interferon
      beta, nine patients (69.2%) had no relapses and the remaining four, experienced
      only one relapse. The mean EDSS score was decreased significantly after the study
      period. The present study provides reasonable data for the use of interferon-beta
      in Pediatric MS due to lack of short-term complications and safety. Studies with
      larger sample size and longer follow up duration are required to shed light on
      the long term impact of the interferon-beta therapy in children.

PMID- 22359078
TI  - Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome.
AB  - Medical therapies have been widely used for premenstrual syndrome (PMS), but in
      all of them side effects are predominant. Herbal remedies rarely have side
      effects and people have more tendencies toward them than chemical therapies. In
      this study the therapeutic effect of Vitex agnus castus on women who had the PMS,
      in comparison with placebo, were investigated. In this randomized, placebo
      controlled, double-blind study, from 134 selected patients 128 women suffered
      from PMS were evaluated (active 62, placebo 66). All patients answered to a self
      assessment questionnaire about their headache, anger, irritability, depression,
      breast fullness and bloating and tympani during the premenstrual period before
      the study. Forty drops of Vitex agnus extract or matching placebo, administrated
      for 6 days before menses for 6 consecutive cycles. Patients answered the self
      assessment questionnaires after 6 menstrual cycles, again. Each item rated using
      a visual analogue scale (VAS). The mean age was 30.77 (SD=4.37) years in the
      active group and 30.89 (SD=4.02) years in the placebo group.Rank of variables had
      significantly difference in active and placebo group before and after the study
      (P<0.0001) also we noticed significant differences on the use of Vitex agnus in
      comparison with placebo (P<0.0001). Vitex agnus can be considered as an effective
      and well tolerated treatment for the relief of symptoms of mild and moderate PMS.

PMID- 22359079
TI  - Comparison of designed slippers splints with the splints available on the market
      in the treatment of hallux valgus.
AB  - Hallux valgus or the lateral deviation of the great toe is a complex disease. If
      it is not treated, it will cause the deviation of other toes. Hallux valgus is
      three times more common in females and may cause uncomfortable deformity of the
      foot, problems in putting on unsuitable and narrow toe box shoes, and pain on the
      medial side of the first metatarsophalangeal joint; therefore, patients seek
      medical services. Untreated hallux valgus may cause the hammer toe deformity of
      the second toe. In this cohort study, 30 patients referring to the Orthopedic
      Clinic of Shohada Ashayer Hospital of Khorramabad, Iran, with a complaint of
      hallux valgus were randomly divided into two groups. The splints designed by the
      researches (slippers splints) were given to the case group, and the splints on
      the market including night splints and interdigital pads were given to the
      control group. The patients were followed every three months for a year and every
      time the weight bearing anteroposterior radiography of both feet were taken and
      hallux valgus and inter-metatarsal angles were measured. The data was analyzed by
      the SPSS software using repeated measure tests. In the case group that used the
      designed splints regularly, hallux valgus angles decreased more dramatically than
      in the control group (P<0.001). This study showed that, despite controversies
      over the nonoperative treatment of hallux valgus, if hallux valgus angle in
      patient is mild to moderate, the splint can be used as a nonoperative treatment.

PMID- 22359080
TI  - Effect of posttraumatic serum thyroid hormone levels on severity and mortality of
      patients with severe traumatic brain injury.
AB  - Traumatic brain injury (TBI) is an important cause of death and disability in
      young adults ,and may lead to physical disabilities and long-term cognitive,
      behavioral psychological and social defects. There is a lack of definite result
      about the effect of thyroid hormones after traumatic brain injury in the severity
      and no data about their effect on mortality of the injury. The aim of this study
      is to evaluate the effect of thyroid hormones after traumatic brain injury in the
      severity and mortality and gain a clue in brain injury prognosis. In a
      longitudinal prospective study from February 2010 until February 2011, we checked
      serum levels of T3, T4, TSH and TBG of severely brain injured patients and
      compared the relationship of them with primary Glasgow Coma Scale (GCS) score and
      mortality of patients. Statistical analysis used SPSS 11.5 software with using
      chi-square and Fisher exact test. Serum levels of T3 and T4 were decreased after
      brain trauma but not TSH and TBG. Mortality rates were higher in patients with
      lower T4 serum levels. The head injury was more severe in whom with low T3 and
      T4. Follow a severe brain injury a secondary hypothyroidism is happened due to
      pituitary dysfunction. Also, serum level of T3 and T4 on the first day admission
      affect on primary GCS score of patients which is an indicator of severity of
      brain injury. In addition, mortality rates of severely brain injured patients
      have a high correlation with the serum level of T4 in the first day admission.

PMID- 22359081
TI  - Right bundle branch block is not a predictor of coronary artery disease.
AB  - Right bundle branch block (RBBB) is considered as an important predictor of poor
      outcome in patients with acute myocardial infarction, but the prognostic
      implication of RBBB in patients with suspected coronary artery disease (CAD) is
      unclear. Furthermore, the association between RBBB and incidence of CAD also its
      influence on the severity of stenosis in coronary arteries has not been
      established. This study was designed to assess the relationship between RBBB and
      the presence and the severity of CAD in patients with suspected CAD. The study
      population consisted of 172 patients with RBBB and 174 patients with normal
      resting electrocardiography (ECG). Severity of CAD was defined as estimated
      Gensini score according to the degree, quantity and distribution of lesions in
      angiographic study. According to our study based on angiographic investigations,
      in patients with RBBB the prevalence of CAD was 77.3 percent versus 70.1 percent
      in patients with normal resting ECG (P=0.13). Also, there was no significant
      association between the presence of RBBB and magnitude of Gensini score (OR=0.87,
      P=0.62). However, male gender and history of diabetes mellitus were associated
      with higher Gensini score (OR=3.41; 95% CI: 1.96-5.93, P<0.0001 and OR=3.22; 95%
      CI: 1.77-5.87, P<0.0001 respectively). This study suggests that although RBBB was
      associated with more severity of stenosis in left coronary system (LAD&LCX), but
      as a whole there was no association between RBBB and the presence and severity of
      CAD.

PMID- 22359082
TI  - Dust exposure and respiratory health effects in cement production.
AB  - Dust can be produced by almost all production processes in Portland cement
      factory. Dust exposure potentially can affect respiratory function. But evidence
      for respiratory effect of cement dust exposure has not been conclusive. In this
      study we assessed effect of cement dust exposure on respiratory function in a
      cement production factory. A respiratory symptoms questionnaire was completed and
      pulmonary function tests were carried out on 94 exposed and 54 non exposed
      workers at a cement factory in the east of Iran. Additionally, respirable dust
      level was determined by the gravimetric method. X-ray fluorescence (XRF)
      technique was performed to determine the silica phases and the SiO(2) contents of
      the bulk samples. The arithmetic means (AM) of personal respirable dust were
      30.18 mg/m(3) in the crushing, 27 mg/m(3) in the packing, 5.4 mg/m(3) in the
      cement mill, 5.9 mg/m(3) in the kiln and 5.48 mg/m(3) in the maintenance that
      were higher than threshold limit value (TLV) of the American Conference of
      Governmental Industrial Hygienists (ACGIH) which is 5 mg/m(3). This value in the
      unexposed group was 0.93 mg/m(3). In this study cough, sputum, wheezing and
      dyspnea were more prevalent among exposed subjects. Exposed workers compared to
      the unexposed group showed significant reduction in Forced Expiratory Volume in
      one second (FEV(1)), Forced Vital Capacity (FVC), and Forced Expiratory Flow
      between 25% and 75% of the FVC (FEF(25-75%)) (P<0.05). It can be concluded that
      in our study there was close and direct association between cement dust exposure
      and functional impairment among the cement factory workers.

PMID- 22359083
TI  - A comparison between craniofacial templates of Iranian and western populations.
AB  - Templates are very useful tools for diagnosis of malocclusions. A number of
      templates have been provided for some populations in previous years. Since
      craniofacial characteristics of different ethnic groups are not the same, each
      population needs its own norms. The aim of this study was to provide orthodontic
      craniofacial templates for 8-16 year old Iranian boys and compare dentoskeletal
      features between Iranian and western populations. 3330 boys with the age range of
      8-16 years were examined in Tehran, and 107 cases were finally chosen for the
      study and their lateral cephalograms were traced. Since there is no universal,
      consensus about the selection of one specific point or line for cephalometric
      superimposition, both the sella nasion (SN) and basion nasion (Ba-N) lines were
      chosen for this purpose. Based on both SN and Ba-N lines, a template was prepared
      for each age. Simple linear regression analysis was used to evaluate the angles
      and the multivariant regression analysis for evaluation of landmark vectors.
      Posterior cranial base, maxillary and mandibular lengths, upper and lower
      anterior facial heights (N-ANS and ANS-Me) and posterior facial height (S-Go) are
      greater in Iranian population. But anterior cranial base, height and inclination
      of the incisors and molar height are similar in two populations.

PMID- 22359084
TI  - Emotional Intelligence in a group of patients with first-episode psychosis in
      Iran.
AB  - This study was aimed to evaluate the Emotional Intelligence (EI) of a group of
      patients with first episode psychosis in Iran as compared with a healthy control
      group. A case-control design was used. EI was assessed using Persian version of
      Bar-On Emotional Quotient inventory (EQ-i) administered on 25 patients with
      history of a single psychotic episode in the last two years, as well as 64
      healthy participants. The mean (+/-SD) of EI scores of patients' and healthy
      controls' group was 319.8 (+/-40.9) and 328.8 (+/-33.3), respectively. Two
      independent sample t-test revealed no significant difference in the EI scores of
      two groups (P=0.29). In contrast with chronic schizophrenia, the patients with
      first-episode psychosis were not different from the healthy subjects in terms of
      emotional intelligence score. It might be implied that the low emotional
      intelligence of the patients with chronic psychotic disorders is an accumulative
      result of the underlying disease over time.

PMID- 22359085
TI  - Life Change Units (LCU) rating as stressors in Iranian hospitals' nurses.
AB  - Healthcare workers suffer from work-related or occupational stress. This can lead
      to severe distress, burnout or physical illness, and finally to decrease quality
      of work life and services provision. Nurses must be aware of retential stressors,
      because they add to the cumulative effect of other stressful events. Holmes and
      Rahe both found a relationship between life change unit as stressors and health
      changes. This research reported here aims to measure the life change units as
      stressors among Iranian Hospitals Nurses by LCU rating. A cross - sectional,
      descriptive and analytical study was conducted among 389 nurses working in 15
      teaching hospitals in Tehran, Iran. The respondents were asked to select each of
      54 events that cause stress ranked in order of their life change units developed
      by Holmes and Rahe as stress scale. Before beginning the main study, the
      reliability and coincidental validity was performed. All data were analyzed using
      SPSS for windows version 18, t-test, Anova statistical methods. Approximately,
      half of the nurses associated major mortgage, foreclosure of mortgage or loan.
      More than 50% of the Iranian nurses had 150-300 and more than 300 LCU rating
      which had the chance to expose to extremely serious risk to health.Iranian
      hospitals nurses suffer from stress that caused by Life Change Units
      organizational factors such as change in the financial state, change in the work
      environment and major mortgage. We recommend to Iranian nursing policy-makers to
      choose strategies to help nurses' cope effectively with workplace stressors.
      Nursing managers and / or nursing management should develop strategies to address
      and improve the quality of working conditions for nurses in the hospitals.
      Providing educational and career prospects can contribute to decrease nurses'
      occupational stress level, the maintaining their work ability.

PMID- 22359086
TI  - Dilated cardiomyopathy in two patients with xeroderma pigmentosum disease: a case
      report.
AB  - Xeroderma pigmentosum (XP), is an autosomal recessive genetic disorder of DNA
      repair in which the ability to repair damage caused by ultraviolet (UV) light is
      deficient. The oxidative stress caused by decline catalase activity as an
      antioxidant enzyme, has been illustrated in these patients. This is the first
      case report of dilated cardiomyopathy in two patients with XP, A 26 year old girl
      and her younger brother. Laboratory studies demonstrated severe vitamin D
      deficiency in both of them. Cardiac dysfunction in the presented cases with XP
      might be caused by vitamin D deficiency. But this question still remains: whether
      chronic oxidative stress can involve the heart and can be a predisposing factor
      or even an underlying factor for dilated cardiomyopathy in XP, or not. More
      studies are needed for demonstrating this hypothesis.

PMID- 22359087
TI  - Base of tongue tuberculosis: a case report.
AB  - We report a rare case of base of tongue tuberculosis following pulmonary
      tuberculosis. Patient presented to us with chief complaints of sore throat and
      pain on swallowing for period of 3 months. On examination with 70 degree
      telescope, we observed an ulcer on right side of base of tongue. The edges of the
      ulcer appeared to be undermined with whitish slough at the centre of the ulcer.
      Examination of neck showed a multiple small palpable middle deep cervical lymph
      nodes on right side of neck. Biopsy of the ulcer was taken, which showed
      granulomatous inflammation, suggestive of tuberculosis. Laboratory investigations
      revealed a raise in erythrocyte sedimentation rate, sputum for acid fast bacilli
      was strongly positive. Chest X ray was performed for patient showed multiple
      areas of consolidation. Patient was referred to chest clinic for further
      management of tuberculosis and was started on anti-tuberculous drugs. In
      conclusion tuberculosis of oral cavity is rare, but should be considered among
      one of the differential diagnosis of the oral lesions and biopsy is necessary to
      confirm the diagnosis.

PMID- 22359088
TI  - Seroepidemiological study of Rift Valley fever (RVF) in animals in Saudi Arabia.
AB  - Serological prevalence of IgG antibodies against Rift Valley fever (RVFV) virus
      was investigated in 22 major localities in five different regions of Saudi Arabia
      where vaccination against RVF virus (RVFV) is not practiced. The study excludes
      the southwestern region where a major outbreak of RVF occurred in 2000 and where
      annual vaccination of ruminants is practiced. Sheep and goat IgG-sandwich ELISA
      were used to test serum samples from sheep and goats, and bovine IgG-sandwich
      ELISA was used to test cattle sera. A nonspecies-specific, nonantibody isotype
      specific ELISA was used to test camel sera. A total of 3,480 sheep, goats, cattle
      and camels with no previous history of vaccination against RVFV were randomly
      tested. All tested animals were negative for IgG class antibodies against the
      virus except four out of 1,508 sheep and three out of 913 goats, which tested
      positive. All animals were clinically normal and no evidence was found of virus
      activity in the studied areas. It is, therefore, most likely that those rare
      positive cases, which constituted 0.002% of the total animals tested, were either
      false positives or vaccinates smuggled from the outbreak zone. The need for
      regular monitoring of animals both within the outbreak zone of 2000 and other
      parts of the kingdom is strongly emphasized.

PMID- 22359089
TI  - Prevalence of antibodies to peste des petits ruminants virus before and during
      outbreaks of the disease in Awash Fentale district, Afar, Ethiopia.
AB  - The present study was conducted to assess the seroprevalence of peste des petits
      ruminants (PPR) in sheep and goats in Awash Fentale district, Afar, Ethiopia.
      Small ruminants in the district had poor herd immunity at the first visit and
      succumb to the disease then after. The seroprevalence during the time of an
      outbreak was much higher compared with the initial levels: 7.3% and 42.6% in
      sheep and goats, respectively. The higher seroprevalence figure in goats was
      suggestive of their relative susceptibility to PPR compared with sheep.

PMID- 22359090
TI  - Evaluation of quantitative sulfur speciation in gas oils by Fourier transform ion
      cyclotron resonance mass spectrometry: validation by comprehensive two
      dimensional gas chromatography.
AB  - Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been
      applied for the quantitative speciation of sulfur containing compounds in gas oil
      (GO). For this purpose, ionization and mass spectrometric parameters have been
      studied and optimized with a set of standard compounds and GO samples.
      Comprehensive two-dimensional gas chromatography (GCxGC) was used as the
      reference method. To allow a quantitative comparison between FT-ICR MS and GCxGC
      results for GO samples, FT-ICR MS parameters were optimized and data obtained by
      both techniques were standardized. Response factors were established for two
      ionization modes: atmospheric pressure photo ionization (APPI) and electrospray
      after selective derivatization of sulfur compounds (MeESI). To test the validity
      of the developed MS methods, a third GO was analyzed and response factors were
      applied. Comparison with GCxGC results showed good agreement for sulfur families
      (deviation within 5% and 15% for MeESI and APPI data, respectively). Abundances
      of individual isomer groups match within 40% in most cases. These results
      principally demonstrate the suitability of FT-ICR MS for a quantitative analysis
      of sulfur compounds (by DBE and carbon number distribution pattern) in petroleum
      middle distillates. This approach has the potential to be extended to higher- and
      non-boiling petroleum fractions where quantitative speciation is presently not
      available.

PMID- 22359091
TI  - An assessment of computational methods for obtaining structural information of
      moderately flexible biomolecules from ion mobility spectrometry.
AB  - When utilized in conjunction with modeling, the collision cross section (Omega)
      from ion mobility spectrometry can be used to deduce the gas phase structures of
      analyte ions. Gas phase conformations are determined computationally, and their
      Omega calculated using an approximate method, the results of which are compared
      with experimental data. Though prior work has focused upon rigid small molecules
      or large biomolecules, correlation of computational and experimental Omega has
      not been thoroughly examined for analytes with intermediate conformational
      flexibility, which constitute a large fraction of the molecules studied in the
      field. Here, the computational paradigm for calculating Omega has been tested for
      the tripeptides WGY, YGW, and YWG (Y = tyrosine, W = tryptophan, G = glycine).
      Experimental data indicate that Omega(exp) (YWG) > Omega(exp) (WGY) ~ Omega(exp)
      (YGW). The energy distributions of conformations obtained from tiers of simulated
      annealing molecular dynamics (SAMD) were analyzed using a wide array of density
      functionals. These quantum mechanical energy distributions do not agree with the
      MD data, which leads to structural differences between the SAMD and DFT
      conformations. The latter structures are obtained by reoptimization of the SAMD
      geometries, and are the only suite of structures that reproduce the experimental
      trend in analyte separability. In the absence of fitting Lennard Jones potentials
      that reproduce experimental results for the Trajectory Method, the Exact Hard
      Sphere Scattering method produced numerical values that are in best agreement
      with the experimental cross sections obtained in He drift gas.

PMID- 22359092
TI  - Atmospheric pressure photoionization as a powerful tool for large-scale lipidomic
      studies.
AB  - Lipidomic studies often use liquid chromatography/electrospray ionization mass
      spectrometry (LC/ESI-MS) for separation, identification, and quantification.
      However, due to the wide structural diversity of lipids, the most apolar part of
      the lipidome is often detected with low sensitivity in ESI. Atmospheric pressure
      (APPI) can be an alternative ionization source since normal-phase solvents are
      known to enhance photoionization of these classes. In this paper, we intend to
      show the efficiency of APPI to identify different lipid classes, with a special
      interest on sphingolipids. In-source APPI fragmentation appears to be an added
      value for the structural analysis of lipids. It provides a detailed
      characterization of both the polar head and the non polar moiety of most lipid
      classes, and it makes possible the detection of all lipids in both polarities,
      which is not always possible with ESI.

PMID- 22359093
TI  - Detection of the spermicide nonoxynol-9 via GC-MS.
AB  - The spermicide nonoxynol-9 is actually a complex mixture of dozens of closely
      related amphiphilic compounds, and the chemical properties of this assortment
      significantly hamper its characterization by GC-MS. The inability to perform
      routine GC-MS testing on nonoxynol-9 has limited its evidentiary value in
      forensic casework, which relies heavily on this technique for analysis. A
      disturbing trend in sexual assault is the use of condoms by assailants, to avoid
      leaving behind DNA evidence that can connect a perpetrator to a victim. This
      observation necessitates the development of alternative methods for the analysis
      of trace evidence that can show causal links between a victim and a suspect.
      Detection of lubricants associated with sexual assault is one such way to
      establish this connection. The development of GC-MS methods that permit facile
      detection of both nonoxynol-9 alone and nonoxynol-9 extracted from other complex
      matrices that have potential as trace evidence in sexual assault is reported. A
      detection limit of 2.14 MUg of nonoxynol-9 is demonstrated, and a detailed mass
      spectral profile that elaborates on what is known of its structure is provided.

PMID- 22359094
TI  - Laser-induced thermal desorption facilitates postsource decay of peptide ions.
AB  - We investigated the thermal mechanism involved in laser desorption/ionization
      (LDI) of thermally labile molecules from the flat surfaces of amorphous Si (a-Si)
      and crystalline Si (c-Si). a-Si was selected for this study because of its
      thermal property, such as low thermal conductivity; thus, it was predicted to be
      highly susceptible to laser-induced surface heating. By virtue of lack of surface
      nanostructures, the flat surfaces offer a simple model system to focus on the
      thermal mechanism, avoiding other effects, including possible non-thermal
      contributions that can arise from the physical existence of surface
      nanostructures. For the energetics study, the internal energies of substituted
      benzylpyridinium ions produced by LDI on the bare and coated surfaces of a-Si and
      c-Si were obtained using the survival yield method. The results, including LDI
      thresholds, ion yields, and internal energies all suggested that the LDI
      mechanism would be indeed thermal, which is most likely promoted by thermal
      desorption caused by laser-induced surface heating. In addition, the LDI process
      driven by laser-induced thermal desorption (LITD) was also found to be capable of
      depositing an excessive internal energy in resulting LDI ions, which underwent a
      dissociation. It exhibited the essentially same features as in postsource decay
      (PSD) in MALDI-TOF/TOF mass spectrometry. We report that the LDI process by LITD
      offers not only a way of intact ionization but also a facile means for PSD of
      peptide ions, which this work demonstrates is well suited to peptide sequencing
      using TOF/TOF mass spectrometry.

PMID- 22359095
TI  - 23rd Sanibel Conference on mass spectrometry: from Fragmentation Mechanisms to
      Sequencing: Tandem Mass Spectrometry Based Peptide and Protein Identification.

PMID- 22359097
TI  - Decreasing radiation therapy utilization in adult patients with glioblastoma
      multiforme: a population-based analysis.
AB  - BACKGROUND: The purpose of this study was to assess what factors influence
      radiation therapy (RT) utilization in patients with glioblastoma and to ascertain
      how patterns of care have changed over time. METHODS: A total of 9103 patients
      with supratentorial glioblastoma in the Surveillance, Epidemiology, and End
      Results (SEER) database from 1973 to 2006 were analyzed. Demographic information
      was obtained, including age, sex, race, year of diagnosis, and marital status.
      Treatment characteristics included receipt of RT and surgical resection. RESULTS:
      In total, 76.8% of patients received RT, whereas 78% received resection. Patients
      of male sex, who were currently married, who were <65 years old, and who
      underwent resection were more likely to receive RT. The average annual percentage
      change in RT utilization in the years 1990-2006 was -0.41% (95% confidence
      interval [CI], -0.23 to -0.58), whereas for resection it was 0.26% (95% CI, 0.03
      to 0.50). This equates to a 6.5% decrease in RT utilization and a 4.2% increase
      in resection during this time period. Patients treated with RT had a 2-year
      overall survival of 11.4%, compared with 5.2% in those not treated with RT (P <
      .00001). Multivariate analysis showed that younger age (continuous; odds ratio
      [OR], 0.97; P < .0001), marital status (OR, 1.62; P < .0001), surgical resection
      (OR, 1.72; P < .0001), and year of diagnosis 1998-2006 compared with 1990-1997
      (OR, 0.82; P < .0001) were associated with RT utilization, whereas sex, lesion
      size, and race were not. CONCLUSIONS: SEER data show a decreasing utilization of
      RT in patients with glioblastoma from 1990 to 2006. Patients who were older, who
      were unmarried, and who underwent biopsy only were less likely to receive RT.

PMID- 22359098
TI  - Consolidated bioprocessing (CBP) of AFEXTM-pretreated corn stover for ethanol
      production using Clostridium phytofermentans at a high solids loading.
AB  - Consolidated bioprocessing (CBP) using Clostridium phytofermentans (ATCC 700394)
      on ammonia fiber expansion (AFEXTM)-treated corn stover (AFEXTM-CS) at a low
      solids loading showed promising results [Jin et al. (2011) Biotechnol Bioeng
      108(6): 1290-1297]. However, industrial relevant process requires high solids
      loading. Therefore, we studied high solids loading CBP performance on AFEXTM-CS.
      The factors potentially affecting the performance including solids loading, CBP
      products acetate and ethanol, and degradation products resulting from
      pretreatment were investigated. At 4% (w/w) glucan loading, C. phytofermentans
      performed well on AFEXTM-CS with no nutrients supplementation and reached similar
      sugar conversions as a fermentation with nutrients supplementation. A glucan
      conversion of 48.9% and a xylan conversion of 77.9% were achieved after 264 h
      with 7.0 g/L ethanol and 8.8 g/L acetate produced. Relatively high concentrations
      of acetate produced at high solids loading was found to be the major factor
      limiting the CBP performance. Degradation products in AFEXTM-CS helped enhance
      ethanol production.

PMID- 22359096
TI  - Family history and APOE-4 genetic risk in Alzheimer's disease.
AB  - Identifying risk factors for Alzheimer's disease, such as carrying the APOE-4
      allele, and understanding their contributions to disease pathophysiology or
      clinical presentation is critical for establishing and improving diagnostic and
      therapeutic strategies. A first-degree family history of Alzheimer's disease
      represents a composite risk factor, which reflects the influence of known and
      unknown susceptibility genes and perhaps non-genetic risks. There is emerging
      evidence that investigating family history risk associated effects may contribute
      to advances in Alzheimer's disease research and ultimately clinical practice.

PMID- 22359099
TI  - A prospective study of bowel preparation for colonoscopy with polyethylene glycol
      electrolyte solution versus sodium phosphate in Lynch syndrome: a randomized
      trial.
AB  - Lynch gene carriers undergo regular surveillance colonoscopies. Polyethylene
      glycol-electrolyte solution (PEG) is routinely prescribed for bowel cleansing,
      but often poorly tolerated by patients. Sodium phosphate (NaP) may be an
      alternative. Prospective and random comparison of bowel preparation with PEG and
      NaP on colon cleansing and patients' acceptance. Patients, who previously
      underwent a colonoscopy, were invited to participate and randomly assigned to
      either PEG or NaP. They were asked to fill in a questionnaire about preparation
      tolerability and future preferences. The endoscopist filled out a report about
      the quality of colon cleansing. 125 Patients were included in the study. Nine
      (7%) were excluded because of missing data. The remaining 116 patients (53 PEG
      and 63 NaP) were included in the analysis. Baseline characteristics did not
      differ between groups. Before colonoscopy 20 (38%) patients using PEG experienced
      the preparation almost intolerable, in contrast to 7(11%) of those using NaP (P =
      0.001). Eleven patients in the PEG group and 48 in the NaP group would prefer NaP
      in the future. The colonoscopy was poorly tolerated in 17% of the individuals in
      both groups (P = 0.963). The endoscopist observed a more than 75% clean colon in
      83% of patients on PEG and in 71% of patients on NaP (P = 0.076), however the
      coecum (P = 0.025) and ascending colon was cleaner after PEG. Lynch patients
      tolerated NaP better and preferred this formula for future bowel preparation.
      Colon cleansing was suboptimal with both treatments with a tendency towards a
      cleaner proximal colon with PEG.

PMID- 22359100
TI  - Neutrophil-active chemokines in in vivo imaging of neutrophil trafficking.
AB  - Chemokines are proinflammatory mediators that regulate leukocyte trafficking at
      different steps of the leukocyte recruitment cascade. Studies using new imaging
      approaches and new mouse models are giving new insights into the role of
      chemokines in neutrophil migration at sites of inflammation. Conventional rolling
      and adhesion paradigms as well as previously unappreciated functions of signaling
      pathways triggering leukocyte adhesion, intralumenal crawling and
      transendothelial migration are compiled and described here. In this review we
      will summarize recent work in this field, highlighting in vivo imaging studies
      that examine the behavior of neutrophils in response to chemokines.

PMID- 22359101
TI  - Ectoenzymes controlling leukocyte traffic.
AB  - Ectoenzymes are a diverse group of membrane proteins that have their catalytic
      sites outside the plasma membrane. Many of them are found on leukocytes and
      endothelial cells, and they are multifunctional in nature. Collectively,
      different ectoenzymes can modulate each step of leukocyte-endothelial contacts,
      as well as subsequent cell migration in tissues. Here, we review how ectoenzymes
      belonging to the oxidase, NAD-metabolizing enzyme, nucleotidase and
      peptidase/protease families regulate and fine-tune leukocyte trafficking, and how
      ectoenzymes have been targeted both in preclinical and clinical trials.

PMID- 22359102
TI  - Transport and cytotoxicity of the anticancer drug 3-bromopyruvate in the yeast
      Saccharomyces cerevisiae.
AB  - We have investigated the cytotoxicity in Saccharomyces cerevisiae of the novel
      antitumor agent 3-bromopyruvate (3-BP). 3-BP enters the yeast cells through the
      lactate/pyruvate H(+) symporter Jen1p and inhibits cell growth at minimal
      inhibitory concentration of 1.8 mM when grown on non-glucose conditions. It is
      not submitted to the efflux pumps conferring Pleiotropic Drug Resistance in
      yeast. Yeast growth is more sensitive to 3-BP than Gleevec (Imatinib
      methanesulfonate) which in contrast to 3-BP is submitted to the PDR network of
      efflux pumps. The sensitivity of yeast to 3-BP is increased considerably by
      mutations or chemical treatment by buthionine sulfoximine that decrease the
      intracellular concentration of glutathione.

PMID- 22359103
TI  - Efficacy and safety of nilotinib in Japanese patients with imatinib-resistant or 
      intolerant Ph+ CML or relapsed/refractory Ph+ ALL: a 36-month analysis of a phase
      I and II study.
AB  - Although the tyrosine kinase inhibitor (TKI) imatinib is often used as first-line
      therapy for newly diagnosed chronic myelogenous leukemia (CML), some patients
      fail to respond, or become intolerant to imatinib. Nilotinib is a potent and
      selective second-generation TKI, with confirmed efficacy and tolerability in
      patients with imatinib-resistant or -intolerant CML. A phase I/II study was
      conducted in Japanese patients with imatinib-resistant or -intolerant CML or
      relapsed/refractory Ph+ acute lymphoblastic leukemia. Thirty-four patients were
      treated with nilotinib for up to 36 months. Major cytogenetic response was
      achieved in 15/16 patients (93.8%) with chronic-phase CML within a median of
      approximately 3 months. Major molecular response was achieved in 13/16 patients
      (81.3%). These responses were sustained at the time of the most recent evaluation
      in 13 patients and 11 patients, respectively. Hematologic and cytogenetic
      responses were also observed in patients with advanced CML. The BCR-ABL mutation
      associated with the most resistance to available TKIs, T315I, was observed in
      three patients. Common adverse events included rash, nasopharyngitis, leukopenia,
      neutropenia, thrombocytopenia, nausea, headache and vomiting. Most adverse events
      resolved following nilotinib dose interruptions/reductions. These results support
      the favorable long-term efficacy and tolerability of nilotinib in Japanese
      patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid
      leukemia.

PMID- 22359104
TI  - Multiple myeloma presenting as cheek tumor.

PMID- 22359105
TI  - Adult hemophagocytic lymphohistiocytosis with severe pulmonary hypertension and a
      novel perforin gene mutation.
AB  - Adult hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly
      hyperinflammatory syndrome presenting both diagnostic and therapeutic challenges.
      HLH may be primary, due to an underlying genetic abnormality, and/or secondary to
      infection, malignancy, or rheumatologic conditions. We describe a case of HLH
      associated severe pulmonary hypertension paralleling Epstein-Barr virus (EBV)
      reactivation in a 52-year-old male in whom a novel perforin missense mutation was
      found (PRF1 1517C>T). Although intolerant of standard therapy (HLH-2004
      protocol), a 6-week course of anti-CD52 (alemtuzumab) was associated with freedom
      from-transfusion from weeks 4 to 13. However, 15 weeks after the onset of salvage
      therapy, he succumbed to polymicrobial sepsis despite treatment with prophylactic
      anti-infectives, with necropsy revealing disseminated blastomycosis and relapsed
      HLH. This case illustrates uncertainties in the relationships between pulmonary
      hypertension, a newly described PRF1 mutation, and possible pre-existing latent
      infectious risk factors (such as EBV or Blastomyces) in the pathogenesis and
      therapeutic perils of adult HLH.

PMID- 22359106
TI  - Managing risks of neoplasia in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) has been linked with a variety of intestinal and
      extraintestinal cancers. This review summarizes the latest literature with regard
      to which cancers are truly linked with IBD and which are not, the absolute and
      relative risks of these cancers, how medications commonly prescribed for IBD
      affect this risk, and finally strategies for managing these risks. Physicians and
      health professionals may find this information useful for counseling and
      educating patients as well as for improving patient care.

PMID- 22359107
TI  - Novel players in inflammatory bowel disease pathogenesis.
AB  - Technological and conceptual advances in inflammatory bowel disease research have
      uncovered new mechanisms that contribute to the pathogenesis of these disorders.
      It is becoming increasingly clear that the microbiota of the gut and the response
      of intestinal cells to that microbiota can initiate or contribute to intestinal
      inflammation. Evidence from genetic studies have identified IBD-associated genes
      implicated in autophagy and innate sensing of microbes. These genes also play key
      roles in the homeostasis of a cell type that stands at the interface of host
      microbial interaction - the Paneth cell. Here we discuss recent findings that
      underscore the importance of the microbiome, Paneth cells and autophagy in
      inflammatory bowel disease.

PMID- 22359109
TI  - Observations on the influence of glutamine, asparagine and peptone on growth and
      t-PA production of Chinese hamster ovary (CHO) cells.
AB  - When a transfected CHO cell, that produces tissue-type Plasminogen Activator, t
      PA, was transferred from a medium based on 5% Fetal Calf Serum, FCS, to a medium
      based on 0.8% casein peptone with variable glutamine and asparagine content, it
      was observed, that the growth of the cells changed from anchorage dependant to
      suspension culture giving more reproducible cultivations. In the FCS culture t-PA
      was unstable, observed as a decline in t-PA concentration after 250 h. This
      decline in t-PA concentration was not observed in the serum free culture,
      although there was a decline in productivity after 200 h. This change in
      production profile may be attributed to either no proteolytic attack from serum
      or by scavenging of proteolytic activities produced by the cells from the peptone
      peptides. Increasing amounts of glutamine/asparagine gave higher production of t
      PA in synchrony with an increasing production of ammonia/ammonium ions. Ammonia
      inhibition does not seem to be a key factor for this cell line as seen with many
      others.

PMID- 22359108
TI  - Clinical significance of programmed cell death 4 expression in malignant
      progression of human nasal inverted papillomas.
AB  - Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene that can inhibit
      tumor neoplastic transformation and progression in cultured cells and gene knock
      out mouse models. Lost or decreased PDCD4 expression has been associated with
      progression and prognosis of multiple types of human tumors. However, the
      expression and clinical significance of PDCD4 in nasal inverted papillomas (NIPs)
      has not been investigated. We compared PDCD4 expression in 64 samples of NIPs, 23
      of associated squamous cell carcinomas (SCCs), and 19 normal nasal samples at
      mRNA and protein levels by RT-PCR, western blot analysis, and
      immunohistochemistry. PDCD4 mRNA expression was reduced in 52% of NIP frozen
      samples (13/25), and the protein level was diminished in 56.3% of samples (36/64)
      as compared with 19 normal nasal samples, which expressed high levels of PDCD4
      mRNA and protein. Furthermore, altered expression of PDCD4 was associated with
      the clinicopathological features Krouse stage and dysplasia. Importantly, we
      found a strong negative correlation of PDCD4 expression and Ki-67 labeling index
      in NIPs (r=-0.6645, p<0.001). In addition, the 3 tissue-sample groups
      significantly differed in PDCD4 expression and Ki-67 labeling index. Thus, PDCD4
      expression may play a key role in pre-cancerous lesions of human NIPs and may
      help predict malignant progression from benign nasal tumors to associated SCC.

PMID- 22359110
TI  - Metabolic rates of vascular endothelial cellsin vitro.
AB  - Cultures of endothelial cells and cell lines of endothelial origin were
      maintained at confluence without medium exchange for a period of 72 h. During
      this time period the concentration of nutrients - amino acids and glucose - and
      metabolic waste products - lactate and ammonium - was determined as well as cell
      vitality and cell numbers. Metabolic rates were calculated and compared for the
      different cell lines. Surprisingly the primary cells showed significantly higher
      rates of glucose and glutamine consumption, respectively lactate production than
      the immortalized cell lines. Except for one tumorigenic cell line all cells
      showed a significant participation of transaminases in glutamine/ammonium
      metabolism. Furthermore it could be shown that in routine culture there was no
      depletion of nutrients or critical accumulation of ammonium or lactate over a
      culture period of 72 h.

PMID- 22359111
TI  - Characteristics of U-937 and HL-60 leukemia cells differentiated by spinach
      extract.
AB  - Some characteristics of U-937 and HL-60 leukemia cell lines treated with a
      fraction of non-dialyzable extract of spinach are reported. The absorbed fraction
      separated by a DEAE-Tyopearl 650 column chromatography of the non-dialyzable
      extract induced NBT reducing activity of U-937 and HL-60 cells. This fraction
      also induced substrate adhesion of U-937 cells, and the non-specific esterase
      activity of HL-60 cells. The expression of CD11b, CD11c and CD36 antigens on the
      U-937 cell surface was enhanced by the treatment with the fraction, whereas CD24
      antigen was not. The treatment of HL-60 cells with the fraction also induced the
      expression of CD11b and CD11c antigens, but CD24 and CD36 were not expressed.
      These results indicated that the non-dialyzable extract of spinach induced
      immature differentiation of U-937 and HL-60 cells into monocyte/macrophages.

PMID- 22359112
TI  - Hepatic resection versus transcatheter arterial chemoembolization for the
      treatment of hepatocellular carcinoma with portal vein tumor thrombus.
AB  - BACKGROUND: The long-term survival outcomes of hepatic resection (HR) compared
      with transcatheter arterial chemoembolization (TACE) for resectable
      hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are
      unclear. MATERIALS AND METHODS: Between December 2002 and December 2007, 201
      consecutive patients diagnosed with resectable HCC with PVTT received HR as an
      initial treatment in our center. These patients were compared with 402 case
      matched controls selected from a pool of 1798 patients (with a 1:2 ratio) who
      received TACE as an initial treatment during the study period. PVTT was
      classified to 4 types: PVTT involving the segmental branches of the portal vein
      or above (type I), PVTT extending to involve the right/left portal vein (type
      II), the main portal vein (type III), or the superior mesenteric vein (type IV).
      RESULTS: The 1-, 3-, and 5-year overall survivals for the HR and TACE groups were
      42.0%, 14.1%, and 11.1% and 37.8%, 7.3%, and 0.5%, respectively (P < .001). On
      subgroup analyses, the overall survivals for the HR group were better than the
      TACE group for type I PVTT, type II PVTT, single tumor, and tumor size >5 cm (P <
      .001, P = .002, P < .001, P < .001, respectively), but not for type III PVTT,
      type IV PVTT, multiple tumors, and tumor size <5 cm (P = .541, P = .371, P =
      .264, P = .338, P = .125, respectively). Multivariate analysis showed the type of
      PVTT and initial treatment allocation were significant prognostic factors for
      overall survival. CONCLUSIONS: Compared with TACE, HR provided survival benefits
      for patients with resectable HCC with PVTT, especially for those with a type I
      PVTT or a type II PVTT.

PMID- 22359113
TI  - Impact of carbon ion radiotherapy for unresectable osteosarcoma of the trunk.
AB  - BACKGROUND: The authors summarized the outcomes of patients with unresectable
      osteosarcoma of the trunk who received carbon ion radiotherapy (CIRT). METHODS:
      The authors performed a retrospective analysis of 78 patients who had medically
      inoperable osteosarcoma of the trunk and received treatment with CIRT between
      1996 and 2009. Tumor sites included the pelvis in 61 patients, the spine and
      paraspinal region in 15 patients, and other sites in 2 patients. The median
      applied CIRT dose was 70.4 Gray equivalent (GyE) in a total of 16 fixed fractions
      over 4 weeks. RESULTS: The minimum duration of follow-up for survivors was 14
      months. Forty-eight patients remained alive. The 5-year overall survival rate was
      33%, and the local control rate was 62%. Thirty-eight patients who had a clinical
      target volume <500 cm(3) had a 5-year overall survival rate of 46% and a 5-year
      local control rate of 88%. Except for 3 patients who experienced severe skin/soft
      tissue complications requiring skin grafts, no other severe toxicities were
      observed. Of 9 patients who were continuously disease free for >5 years, 8 were
      able to walk with or without the help of a cane, and 6 were free from pain
      killers. CONCLUSIONS: CIRT appeared to be a safe and effective modality for the
      management of unresectable osteosarcoma of the trunk, providing good local
      control and offering a survival advantage and good long-term functional results
      without unacceptable morbidity.

PMID- 22359115
TI  - Erratum.

PMID- 22359117
TI  - Transfection of cultured fish cells with exogenous DNA.
AB  - We have applied to fish cell cultures the techniques used routinely to introduce
      exogenous genes into cultured mammalian cells. Using calcium phosphate-mediated
      transfection, a plasmid containing bacterial aminoglycoside phosphotransferase
      under the influence of the simian virus 40 early promoter and polyadenylation
      signal was introduced into several fish cell lines. The plasmid was expressed in
      these cells in a stable manner, with transfection occurring at a frequency
      comparable to that seen with mammalian cells. These results suggest that plasmids
      constructed for use in mammalian cells may be used efficiently in fish systems
      without further modification and indicate that the advantages of transfection
      procedures utilized in mammalian systems can also be applied to fish.

PMID- 22359118
TI  - Growth inhibition of cartilaginous embryonic chick tibiae by ionizing radiation:
      an in vitro study.
AB  - The radiation effect on the longitudinal growth of cartilaginous tibiae of 6,5
      day old chick embryos is studied in vitro. After irradiation length is measured
      daily during the 3 days culture period and incorporation of (3)H-thymidine, (3)H
      uridine or (3)H-proline is sampled by liquid scintillation counting. Selective
      tibiae are videorecorded during the incubation period. Morphology is studied by
      light microscopy, autoradiography and electron microscopy.Growth inhibition is
      only restricted to 5% at 20 Gy up to 20% at 150 Gy. The (3)H-uridine and (3)H
      proline incorporation is only decreased by 21 and 32% at 150 Gy. (3)H-thymidine
      incorporation on the contrary shows 17% decrease at 2 Gy. Irradiation at 200 Gy
      gives a total growth arrest and stops incorporation of all used labeled compounds
      in 75% of the specimens. L.M. and E.M. show no morphological differences between
      irradiated and sham irradiated tibiae until 150 Gy. At 200 Gy however necrosis of
      the cells is observed.We conclude that longitudinal growth of cartilaginous
      tibiae in organ culture is not correlated with DNA synthesis but with cell
      hypertrophy and production of extracellular material. RNA transcription and
      synthesis of collagen fibers are radioresistant processes. This explains the
      limited influence of irradiation on the longitudinal growth.

PMID- 22359116
TI  - Media for cultivation of animal cells: an overview.
AB  - The increasing interest in products from animal cells has caused an extensive
      research effort towards development of media for cell cultivation.The basic
      components in the media used for cultivation of animal cells vary depending upon
      the characters of the cells and the cultivation method. Basic components consist
      of an energy source, nitrogen source, vitamins, fats and fatty soluble
      components, inorganic salts, nucleic acid precursors, antibiotics, oxygen, pH
      buffering systems, hormones, growth factors and serum. Extensive efforts are
      directed towards developing serum-free or chemically defined media. Among the
      serum substitutes is a long list of hormones and growth factors.

PMID- 22359119
TI  - Characterization and applications of lymphocytic clonal growth factor in human
      plasma.
AB  - Human plasma was found to contain a macromolecular protein which can grow even a
      single cell of human lymphocytic cell lines (B-lymphoblastoid cell line HO-323-3
      and T-lymphoblastoid cell line CCRF-CEM) and human-human hybridoma clones (SH-9,
      SU-1 and HB4C5) in a dish, but it has no effect on the growth of epithelial cell
      lines (lung cancer cell lines PC-8, QG-56 and QG-90). The proliferating activity
      for lymphocytic cell lines was gradually decreased at 4 or -20 degrees C and
      dramatically decreased by heating at more than 60 degrees C for 15 min. From
      human plasma, active fractions were purified by a successive application of
      Ca(2+) treatment, ammonium sulfate fractionation, DEAE-5PW column chromatography
      (FPLC) at pH 7.6. These active fractions were divided into at least three
      proteins by DEAE-5PW chromatography at pH 8.5 and chromatofocusing. These
      purified factors, named lymphocytic clonal growth factors (LCGFs), had similar
      molecular weights of about 600 K and each factor consisted of a 180 K and two 210
      K subunits associated with hydrogen bondings. By the addition of 5 MUg/ml of each
      factor into culture media, incidences of human-human hybridomas and cloning
      efficiencies of the hybridomas increased several-fold.

PMID- 22359114
TI  - Molecular analysis of a sunflower gene encoding an homologous of the B subunit of
      a CAAT binding factor.
AB  - A genomic DNA fragment containing the complete LEAFY COTYLEDON1-LIKE (HaL1L) gene
      was retrieved by chromosome walking. Its sequence was confirmed and elongated by
      screening a sunflower genomic DNA BAC Library. HaL1L, whose cDNA had already been
      sequenced and characterized, encodes a NF-YB subunit of a CCAAT box-binding
      factor (NF-Y) involved in the early stages of zygotic and somatic embryogenesis
      in the Helianthus genus. In the HaL1L 5'-flanking region, elements specific to a
      putative TATA-box promoter and two "CG isles" were identified. An investigation
      of the methylation status of these CG rich DNA regions showed that differentially
      methylated cytosines were recognizable in the DNA of embryos on the fifth day
      after pollination in comparison to leaf DNA suggesting that during plant
      development epigenetic regulation of HaL1L transcription was achieved by
      methylating cytosine residues. We also searched the HaL1L nucleotide sequence for
      cis-regulatory elements able to interact with other transcription factors (TFs)
      involved in the HaL1L regulation. Of the elements identified, one of the most
      intriguing is WUSATA, the target sequence for the WUSCHEL (WUS) TF, which may be
      part of a complex regulation network controlling embryo development. In this
      article, we show that the WUSATA target site, located in the intron of HaL1L, is
      able to bind the TF WUS. Interestingly, we found auxin and abscisic acid
      responsive motifs in the HaL1L promoter region suggesting that this gene may
      additionally by under hormonal control. Finally, the presence of a cytoplasmic
      polyadenylation signal downstream to the coding region indicates that this gene
      may also be controlled at the translation level by a temporarily making the pre
      synthesized HaL1L mRNA unavailable for protein synthesis.

PMID- 22359121
TI  - Simple manual method for making cell smears of leukapheresis and cell culture
      products: application to human LAK cell laboratories.

PMID- 22359120
TI  - Formation of multilayer rosettes in phytohemagglutinin-stimulated lymphocytes:
      correlation with chromatin condensation conformation in premature chromosome
      condensation.
AB  - We found that the formation of multilayer rosettes by transformed human blood
      lymphocytes after phytohemagglutinin (PHA) stimulation is correlated with
      conformational changes of the chromatin as seen by premature chromosome
      condensation (PCC). The frequency distribution of grades of PCC and multilayer
      rosette formation suggests that changes in chromatin are a prerequisite for
      rosette formation. Rosette formation was most pronounced for 24-h and 48-h
      cultures. Chromatin decondensation and rosette formation showed identical
      patterns. The possibility that multilayer rosette formation is directly dependent
      on conformational changes of chromatin is discussed.

PMID- 22359122
TI  - A simple freezing medium for serum-free cultured cells.
AB  - Methylcellulose was found to protect serum-free cultured cells from the
      deleterious effects of freezing and thawing. We have formulated a simple medium
      suitable for freezing serum-free cultured cells that consists of 0.1%
      methylcellulose, 10% dimethylsulfoxide, and MEM or any other serum-free culture
      medium.

PMID- 22359123
TI  - An in vitro test for measuring cytotoxicity of mercuric chloride to human kidney
      epithelial cells by specific enzyme release.
AB  - Mercuric compound toxicity is well documented in animals and man for practically
      all organs. The recent development of cell culture techniques appeared as a novel
      fruitful tool in toxicology, especially in renal toxicology. Heavy metal induced
      renal cell alterations can be evaluated by membrane permeability damages.The
      present study evaluates mercuric chloride nephrotoxic effect in human kidney
      epithelial cells by measuring the release of two specific nephrotoxicity marker
      enzymes, Gamma Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP) in the
      culture medium. Cultured kidney epithelial cells were exposed to different
      HgCl(2) concentrations (5, 10, 20, and 50 MUg). Cultures were examined after 6
      and 24 hours exposure. A good correlation between mercury dose and toxic effect,
      and exposure time and toxic effect was found. Enzymes were significantly released
      into the culture medium for 5 MUg and 10 MUg HgCl(2)/ml after 6 hours exposure;
      and after 24 hours exposure, enzymes were released for 5 MUg/ml only.It appears
      that the specific tubular enzyme release in the culture medium is a good in vitro
      test for quantification of specific tubular damage.

PMID- 22359125
TI  - Erratum.

PMID- 22359124
TI  - ETCS-UK meeting on cell culture in serum-free media (UMDS, St. Thomas' Campus 3-4
      Nov 1987).

PMID- 22359126
TI  - World Voice Day 2012.

PMID- 22359128
TI  - Reactive intracordal fibrovascular lesion.

PMID- 22359129
TI  - Endoscopic view of a frontal recess obstruction causing frontal sinusitis.

PMID- 22359131
TI  - Parotidectomy for treatment of bulimic parotid hypertrophy.

PMID- 22359132
TI  - Percutaneous injection pharyngoplasty for the treatment of a pharyngocele.

PMID- 22359133
TI  - Outcomes of endoscopic sphenopalatine artery ligation for epistaxis: a five-year
      series from a single institution.
AB  - Epistaxis is a common emergency seen by the otolaryngologist. A minority of cases
      require surgical intervention. Multiple surgical procedures have been tried in
      the past, including endoscopic ligation of the sphenopalatine artery (ELSPA),
      which is considered an effective surgical modality in the management of
      epistaxis. This study examines the outcome of 33 ELSPA procedures over a 5-year
      period. Three of 4 cases that were not controlled with ELSPA were successfully
      managed with subsequent anterior ethmoidal ligation. Failed ELSPA procedures may
      represent an incorrect choice of procedure rather than a failure of the
      procedure. High-resolution computed tomography can identify the position of the
      anterior ethmoidal artery; it may be possible to infer vulnerability to
      hemorrhage from this artery and hence target procedure selection.

PMID- 22359134
TI  - Report of a sphenoid sinus lipoma.
AB  - Sphenoid sinus opacification on computed tomography can represent a multitude of
      etiologies. Such a finding can signify an infectious, inflammatory, congenital,
      neuronal, vascular, or neoplastic mass. In this article, we describe a case of a
      lipoma of the sphenoid sinus, and we discuss the differential diagnosis and
      management of this finding.

PMID- 22359135
TI  - Atypical carcinoid (moderately differentiated neuroendocrine carcinoma) of the
      uvula.
AB  - Carcinoid (neuroendocrine) tumors of the head and neck rarely occur outside the
      larynx and, until now, none has been reported in the oral cavity. We describe
      what we believe is the first reported case of an atypical carcinoid tumor, or any
      other type of neuroendocrine carcinoma, of the uvula.

PMID- 22359136
TI  - Myxoid/round cell liposarcoma of the supraclavicular fossa.
AB  - Metastases from the tracheobronchial tree and the genitourinary and
      gastrointestinal systems are the most common malignant lesions of the
      supraclavicular fossa. Liposarcomas in this region, as primary tumors, are rarely
      encountered. In this article, we report a case of myxoid liposarcoma of the
      supraclavicular fossa with a fulminant course.

PMID- 22359137
TI  - Giant chondroma of the head and neck causing gross facial deformity.
AB  - Cartilaginous tumors in the head and neck region are rare. We report the case of
      a middle-aged man with a progressive swelling in the left cheek area who had been
      seen several times over the years at our otorhinolaryngology department. The
      progression of the swelling culminated in an extremely large tumor that grossly
      distorted the patient's face. Examination revealed that the mass had probably
      originated in the maxillary sinus; it eventually extended to the skull base,
      middle cranial fossa, and cavernous sinus. Several histologic examinations of
      biopsy specimens identified the mass as a chondroma. The unusual size and
      extension of the tumor indicated extensive surgery, but the patient refused. We
      discuss the natural history of this tumor, and we review the current literature
      on head and neck chondromas.

PMID- 22359138
TI  - Folliculosebaceous cystic hamartoma of the external auditory canal in an adult.
AB  - Folliculosebaceous cystic hamartoma (FSCH) is a cutaneous hamartoma of
      pilosebaceous origin that usually occurs on the face. We present what we believe
      is only the second reported case of FSCH of the external auditory canal, and the
      first in an adult. The patient was a 59-year-old woman who presented with a 4
      year history of a firm nodule on the left external auditory canal that had caused
      hearing loss, pruritus, and pain. The lesion was excised, and histopathologic
      examination identified infundibular cysts, hyperplasia of the sebaceous lobules,
      and a large amount of mucin, features that are consistent with FSCH. One year
      postoperatively, the patient was asymptomatic, and no evidence of recurrence was
      noted.

PMID- 22359139
TI  - A case of extranasopharyngeal angiofibroma of the ethmoid sinus: a distinct
      clinical entity at an unusual site.
AB  - Angiofibromas of the head and neck usually arise from the nasopharynx in
      adolescent boys. The term extranasopharyngeal angiofibroma (ENA) has been applied
      to vascular fibrous nodules that arise outside the nasopharynx. Because the
      clinical characteristics of ENA are not consistent with those of juvenile
      nasopharyngeal angiofibroma (JNA), diagnosis of the former can be challenging.
      Biopsy is ill advised in a patient with an ENA because it might result in brisk
      bleeding. A high index of suspicion and a methodical evaluation are essential in
      establishing the proper diagnosis and treatment. We report the rare case of a 16
      year-old girl who presented with a pinkish lobulated mass in her left nostril
      that had arisen from the anterior ethmoid sinus. The mass was removed via a
      lateral rhinotomy approach. Postoperative histopathologic analysis identified it
      as an angiofibroma. To best of our knowledge, only 9 cases of ENA arising from
      the ethmoid sinus have been previously reported in the English-language
      literature.

PMID- 22359140
TI  - Endolaryngeal lipoma: case report and literature review.
AB  - Lipomas are the most common benign tumors affecting the soft tissues. They can
      occur at any age, but they typically appear in patients older than 40 years. They
      are found equally in men and women. Lipomas are uncommon in the head and neck,
      but when they do appear there, they can arise in any location, including the
      palate, tongue, tonsil, larynx, and parotid gland. We report the case of a 63
      year-old man who presented to the emergency department with a large spindle-cell
      lipoma of the endolarynx. The patient was followed for 6 months, and he exhibited
      no snoring or breathing difficulties.

PMID- 22359141
TI  - Pertussis presenting as hoarseness in an adult.
AB  - Pertussis is a rare condition in adults. This report describes a 65-year-old man
      presenting to the otolaryngology service with hoarseness secondary to pertussis.
      He had a history of worsening cough and hoarseness occurring over several weeks.
      Laryngoscopy showed significant erythema at the medial edges of the vocal folds.
      Stroboscopy demonstrated bilateral decreased amplitude and decreased mucosal wave
      of the vocal folds. Polymerase chain reaction testing of the sputum revealed
      Bordetella pertussis. The patient was started on azithromycin, and he reported
      gradual resolution of the chest and laryngeal symptoms over the next few months.
      Pertussis, or whooping cough, is not common in the United States because of
      childhood vaccination protocols. Nevertheless, otolaryngologists need to be aware
      of this condition as a possible cause of hoarseness.

PMID- 22359142
TI  - Suboccipital malignant solitary fibrous tumor: report of a case.
AB  - Solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas usually arising in
      the pleura of the thoracic cavity. Thirty percent of SFTs present in extrapleural
      locations, and infrequently in the head and neck region. While the majority of
      SFTs are benign, aggressive variants have been described. We report a case of a
      patient with a malignant SFT arising in the suboccipital soft tissues of the
      neck. We elucidate the diagnostic and therapeutic challenges in managing this
      tumor in this unusual location.

PMID- 22359143
TI  - Ectodermal dysplasia: otolaryngologic evaluation of 23 cases.
AB  - The aim of this prospective study was to improve the quality of life of and
      reduce morbidity for patients with ectodermal dysplasia by assessing their actual
      and potential ENT pathologies, and offering methods of prevention and treatment.
      The study was conducted between 2006 and 2008 and included 23 patients diagnosed
      with ectodermal dysplasia. The major symptoms of ectodermal dysplasia were
      evaluated. Patient histories were obtained in all cases, and a complete head and
      neck examination was carried out. Of the 23 patients (11 males and 12 females,
      aged 5 to 45 years) diagnosed with ectodermal dysplasia, 22 had hypohidrotic
      ectodermal dysplasia and 1 had ectrodactyly-ectodermal dysplasia-clefting
      syndrome. In all patients diagnosed with hypohidrotic ectodermal dysplasia, the
      salivary glands were examined by ultrasonography and, when necessary, by
      scintigraphy. Hearing defects in patients with otologic problems were determined
      by audiometric examination: 39.1% of the patients had hearing loss, 43.5% had
      otitis media, and 39.1% had impacted cerumen. The most common rhinologic findings
      were saddle nose deformity in 56.5%, nasal obstruction and nasal dryness (52.2%
      each), and chronic rhinitis/rhinosinusitis (34.8%). The most common oral and
      oropharyngeal findings were difficulty chewing in 82.6% and dry mouth in 78.3%.
      All 23 patients had required dental work. Because this disorder affects several
      aspects of the body, its treatment requires a multidisciplinary approach, with
      the otolaryngologist being a vital part of the management team.

PMID- 22359144
TI  - Middle ear encephalocele: not just another chronic ear.

PMID- 22359145
TI  - Sphenopalatine artery pseudoaneurysm after endoscopic sinus surgery: a case
      report and literature review.
AB  - Previously reported cases of iatrogenic sphenopalatine artery (SPA)
      pseudoaneurysm have occurred only after trans-sphenoidal surgery for pituitary
      tumors or maxillofacial surgery. In this article, the author presents what to the
      best of her knowledge is the first reported case of an SPA pseudoaneurysm that
      developed following endoscopic sinus surgery (ESS). The patient was a 76-year-old
      woman with myelodysplastic syndrome who presented with a 6-month history of
      unilateral sinus symptoms. She underwent septoplasty and unilateral ESS, which
      included frontal recess clearance and sphenoidotomy. However, during surgery,
      severe generalized bleeding was encountered. The bleeding was arrested only after
      anterior and posterior nasal packing. After two attempts to remove the packing
      failed, angiography was obtained. It revealed an SPA pseudoaneurysm, which was
      immediately and successfully embolized. SPA pseudoaneurysm is a rare but
      significant complication of ESS, and it should be considered in patients with
      posterior epistaxis after ESS or prolonged posterior nasal packing. The
      pathogenesis may include intraoperative trauma, infection, pressure necrosis from
      packing, or a combination of these factors. Optimal management includes either
      ligation or embolization, depending on anatomic, patient, staff, and resource
      factors. The author reviews the pertinent anatomy and the pathophysiology,
      diagnosis, management, and prevention of this rare complication.

PMID- 22359146
TI  - Simultaneously improving the mechanical properties, dissolution performance, and
      hygroscopicity of ibuprofen and flurbiprofen by cocrystallization with
      nicotinamide.
AB  - PURPOSE: To be fully exploitable in both formulation and manufacturing, a drug
      cocrystal needs to demonstrate simultaneous improvement of multiple key
      pharmaceutical properties over the pure drug crystal. The present work was aimed
      at investigating such feasibility with two model profen-nicotinamide cocrystals.
      METHODS: Phase pure 1:1 ibuprofen-nicotinamide and flurbiprofen-nicotinamide
      cocrystals were prepared from solutions through rapid solvent removal using
      rotary evaporation,and characterized by DSC, PXRD, FTIR, phase solubility
      measurements, equilibrium moisture sorption analysis, dissolution testing and
      tabletability analysis. RESULTS: Temperature-composition phase diagrams
      constructed from DSC data for each profen and nicotinamide crystal revealed the
      characteristic melting point of the 1:1 cocrystal as well as the eutectic
      temperatures and compositions. Both cocrystals exhibited higher intrinsic
      dissolution rates than the corresponding profens. The cocrystals also sorbed less
      moisture and displayed considerably better tabletability than the individual
      profens and nicotinamide. CONCLUSIONS: Phase behaviors of 1:1 profen-nicotinamide
      cocrystal systems were delineated by constructing their temperature-composition
      phase diagrams. Cocrystallization with nicotinamide can simultaneously improve
      tableting behavior, hygroscopicity, and dissolution performance of ibuprofen and
      flurbiprofen. This could pave the way for further development of such cocrystal
      systems into consistent, stable, efficacious and readily manufacturable drug
      products.

PMID- 22359147
TI  - LCDs are better: psychophysical and photometric estimates of the temporal
      characteristics of CRT and LCD monitors.
AB  - Many cognitive and perceptual phenomena, such as iconic memory and temporal
      integration, require brief displays. A critical requirement is that the image not
      remain visible after its offset. It is commonly believed that liquid crystal
      displays (LCD) are unsuitable because of their poor temporal response
      characteristics relative to cathode-ray-tube (CRT) screens. Remarkably, no
      psychophysical estimates of visible persistence are available to verify this
      belief. A series of experiments in which white stimuli on a black background
      produced discernible persistence on CRT but not on LCD screens, during both dark-
      and light-adapted viewing, falsified this belief. Similar estimates using black
      stimuli on a white background produced no visible persistence on either screen.
      That said, photometric measurements are available that seem to confirm the poor
      temporal characteristics of LCD screens, but they were obtained before recent
      advances in LCD technology. Using current LCD screens, we obtained photometric
      estimates of rise time far shorter (1-6 ms) than earlier estimates (20-150 ms),
      and approaching those of CRTs (<1 ms). We conclude that LCDs are preferable to
      CRTs when visible persistence is a concern, except when black-on-white displays
      are used.

PMID- 22359148
TI  - Copper and cadmium removal from synthetic industrial wastewater using chitosan
      and nylon 6.
AB  - PURPOSE: Chitosan with nylon 6 membranes was evaluated as adsorbents to remove
      copper and cadmium ions from synthetic industrial wastewater. METHODS: Chitosan
      and nylon 6 with glutaraldehyde blend ratio with (1:1+Glu, 1:2+Glu, and 2:1+Glu)
      have been prepared and these were used as membranes to remove copper and cadmium
      ions from synthetic industrial wastewater. Characterization of the synthesized
      membrane has been done with FTIR, XRD, TGA/DTA, DSC, and SEM. Chemical parameters
      for quantities of adsorption of heavy metal contamination have been done and the
      kinetics of adsorption has also been carried out. RESULTS: The optimal pH for the
      removal of Cd(II) and Cu(II) using chitosan with nylon 6. Maximum removal of the
      metals was observed at pH 5 for both the metals. The effect of adsorbent dose
      also has a pronounced effect on the percentage of removal of the metals. Maximum
      removal of both the metals was observed at 5 g/100 ml of the adsorbent.
      CONCLUSION: Copper and cadmium recovery is parallel at all time. The percentage
      of removal of copper increased with increase in the pH from 3 to 5. In the case
      of cadmium containing wastewater, the maximum removal of metal occurred at pH 5.
      The uptake amount of Cu(2+) ions on chitosan increased rapidly with increasing
      contact time from 0 to 360 min and then reaches equilibrium after 360 min; the
      equilibrium constant for copper and cadmium ions is more or less the same for the
      adsorption reaction.

PMID- 22359149
TI  - Longitudinal associations between perceived parent-adolescent attachment
      relationship quality and generalized anxiety disorder symptoms in adolescence.
AB  - This longitudinal study examined the direction of effects between adolescents'
      generalized anxiety disorder (GAD) symptoms and perceived parent-adolescent
      attachment relationship quality, as well as the moderating role of gender and
      age. 1,313 Dutch adolescents (48.5% boys) from two age cohorts of early (n = 923,
      M(age) = 12 at W1) and middle (n = 390, M(age) = 16 at W1) adolescents completed
      questionnaires regarding their attachment relationship to parents and GAD
      symptoms in four waves. Cross-lagged path analyses demonstrated that adolescents'
      GAD symptoms and perceived father-adolescent attachment relationship quality
      bidirectionally negatively affected each other over time. For mothers,
      adolescents' GAD symptoms negatively predicted perceived mother-adolescent
      attachment relationship quality over time. The within-wave correlated residuals
      between perceived attachment relationship quality with fathers and GAD symptoms
      were stronger for boys than for girls and stronger for the cohort of middle
      adolescents than for the cohort of early adolescents. This study demonstrates
      that both the parents' and the adolescents' gender as well as the adolescents'
      age affects the relation between adolescents' GAD symptoms and perceived parent
      adolescent attachment relationship quality.

PMID- 22359150
TI  - Ubiquitous Acinetobacter species as beneficial commensals but gradually being
      emboldened with antibiotic resistance genes.
AB  - Acinetobacter spp. are ubiquitous obligate aerobic bacteria which occur mostly as
      commensals on the skin, and in soil, water and plants' rhizosphere. Though the
      species in this genus have been implicated as aetiologies in some nosocomial
      infections, their versatility covers biodegradation or dissolution leading to
      bioremediation; catalysis leading to synthesis of high molecular weight, life
      sustaining polymers; and as growth enhancers in agriculture. The challenge of
      antibiotic resistance and their mediatory genes is a cause for concern but should
      not deter the beneficial application of the bacteria especially in the synthesis
      of novel compounds that would be of relevance in overcoming some global
      ecological challenges. This review addresses important beneficial attributes of
      Acinetobacter species as well as gives some insight into emerging trends in their
      resistance to antibiotics.

PMID- 22359151
TI  - Efficacy and safety of long-term botulinum toxin treatment in craniocervical
      dystonia: a systematic review.
AB  - Botulinum neurotoxins have been shown to be a safe and effective therapeutic
      option for most forms of focal dystonia, and are now considered to provide the
      best symptomatic treatment in these disorders. However, only a few papers
      addressed the long-term efficacy and safety of repeated treatments with this
      drug. This article reviews the data from clinical trials that have assessed the
      long-term results of botulinum neurotoxin type A (BoNT-A) and type B in the
      treatment of the different forms of focal craniocervical dystonia, cervical
      dystonia (CD), blepharospasm, oromandibular, and laryngeal dystonia. Studies on
      the long-term effects of BoNT-A therapy have demonstrated that the majority of
      patients comply with this repeated treatment because they experience a positive
      and stable effect over time. It is still unclear whether in patients with focal
      dystonia the mean dose of BoNT-A changes over time. In spite of the wide spectrum
      of side effects reported to be associated with BoNT-A treatment, there is no
      evidence of specific side effects due exclusively to the long-term use of such
      drugs. The only exception to these positive long-term findings is the occurrence
      of a subgroup of patients with CD who fail to maintain a sustained response after
      the first or second effective treatment, partly owing to the development of
      neutralizing antibodies against the toxin. Longitudinal studies aimed at defining
      the risk factors for this abnormal pattern of response to botulinum toxin
      treatment are currently being conducted.

PMID- 22359152
TI  - Characterization of an antifungal compound produced by Bacillus sp. strain A(5) F
      that inhibits Sclerotinia sclerotiorum.
AB  - A potential antagonist, Bacillus sp. strain A(5) F was isolated from soybean
      rhizosphere following in vitro dual plate screening. The bacterium displayed
      strong inhibitory activity in vitro against soybean stem rot pathogen,
      Sclerotinia sclerotiorum. The culture supernatant of strain A(5) F completely
      suppressed the mycelial growth of the pathogen, indicating that suppression was
      due to the presence of antifungal compounds in the culture filtrate. The culture
      filtrate also suppressed other phytopathogenic fungi including Fusarium oxysporum
      and Macrophomina phaseolina, in vitro suggesting a broad spectrum antagonistic
      activity against fungal pathogens. Chemical extraction followed by
      chromatographic analysis resulted in two antifungal fractions. The high
      resolution-electron spin ionization-mass spectrometry (HR-ESI-MS) and Nuclear
      Magnetic Resonance (1D and 2D(1) H) spectra of these antifungal fractions
      revealed the presence of antifungal compounds, one of which showed similarity to
      bacillomycin D.

PMID- 22359153
TI  - Growth and metabolism of human tumor kidney cells on galactose and glucose.
AB  - The culture kinetics of human tumor kidney cells (TCL 598) grown on microcarriers
      are compared with media initially supplemented with either glucose alone or a
      mixture of galactose and glucose. Growth rates and maximal cell densities are
      similar, but cellular death is much slower in galactose than in glucose.
      Galactose is metabolized at a much slower specific rate than glucose. Cells grown
      in the galactose medium show a different pattern of lactate and pyruvate
      metabolism compared to cells grown in the glucose medium. Growth with galactose
      also favours oxidation of glutamine to alanine.

PMID- 22359154
TI  - Introduction : Changing frontiers in cell culture engineering: Manipulating cell
      biology to improve process technology.

PMID- 22359155
TI  - Molecular identification and antifungal susceptibilities of black Aspergillus
      isolates from otomycosis cases in Hungary.
AB  - Otomycosis, also known as fungal otitis externa, has been used to describe a
      fungal infection of the external auditory canal, but sometimes involving the
      middle ear. Many fungal species have been identified as infectious agents in
      otomycosis, with Aspergillus and Candida species being the most common. Among
      aspergilli, Aspergillus niger is the most commonly described species in the
      literature. In this study, 14 black Aspergillus strains were analyzed, which were
      isolated from otomycosis cases in Hungary between 2010 and 2011. These strains
      were identified as A. niger according to conventional morphological methods.
      Species identification was based on sequencing of part of the calmodulin gene.
      Our results indicate that instead of A. niger, A. awamori and A. tubingensis are
      the predominant species that cause ear infections in Southern Hungary. Antifungal
      susceptibility tests were carried out against four antifungal drugs: amphotericin
      B, itraconazole, ketoconazole and terbinafine. All isolates were found to exhibit
      low in vitro MIC values to amphotericin B, terbinafine and itraconazole. However,
      the examined isolates exhibited high in vitro MIC values to ketoconazole.

PMID- 22359156
TI  - Purpose in life and reduced risk of myocardial infarction among older U.S. adults
      with coronary heart disease: a two-year follow-up.
AB  - This study examined whether purpose in life was associated with myocardial
      infarction among a sample of older adults with coronary heart disease after
      adjusting for relevant sociodemographic, behavioral, biological, and
      psychological factors. Prospective data from the Health and Retirement Study-a
      nationally representative panel study of American adults over the age of 50-were
      used. Analyses were conducted on the subset of 1,546 individuals who had coronary
      heart disease at baseline. Greater baseline purpose in life was associated with
      lower odds of having a myocardial infarction during the 2-year follow-up period.
      On a six-point purpose in life measure, each unit increase was associated with a
      multivariate-adjusted odds ratio of 0.73 for myocardial infarction (95% CI, 0.57
      0.93, P = .01). The association remained significant after controlling for
      coronary heart disease severity, self-rated health, and a comprehensive set of
      possible confounds. Higher purpose in life may play an important role in
      protecting against myocardial infarction among older American adults with
      coronary heart disease.

PMID- 22359157
TI  - Overview of regulatory strategies and molecular elements in metabolic engineering
      of bacteria.
AB  - From a viewpoint of biotechnology, metabolic engineering mainly aims to change
      the natural status of a pathway in a microorganism towards the overproduction of
      certain bioproducts. The biochemical nature of a pathway implies us that changed
      pathway is often the collective results of altered behavior of the metabolic
      enzymes encoded by corresponding genes. By finely modulating the expression of
      these genes or the properties of the enzyme, we can gain efficient control on the
      pathway. In this article, we reviewed the typical methods that have been applied
      to regulate the expression of genes in metabolic engineering. These methods are
      grouped according to the operation targets in a typical gene. The transcription
      of a gene is controlled by an indispensable promoter. By utilizing promoters with
      different strengths, expected levels of expression can be easily achieved, and
      screening a promoter library may find suitable mutant promoters that can provide
      tunable expression of a gene. Auto-responsive promoter (quorum sensing (QS)-based
      or oxygen-inducible) simplifies the induction process by driving the expression
      of a gene in an automated manner. Light responsive promoter enables reversible
      and noninvasive control on gene activity, providing a promising method in
      controlling gene expression with time and space resolution in metabolic
      engineering involving complicated genetic circuits. Through directed evolution
      and/or rational design, the encoding sequences of a gene can be altered, leading
      to the possibly most profound changes in properties of a metabolic enzyme.
      Introducing an engineered riboswitch in mRNA can make it a regulatory molecule at
      the same time; ribosomal binding site is commonly engineered to be more
      attractive for a ribosome through design. Terminator of a gene will affect the
      stability of an mRNA, and intergenic region will influence the expression of many
      related genes. Improving the performance of these elements are generally the main
      activities in metabolic engineering.

PMID- 22359158
TI  - Moringa coagulant as a stabilizer for amorphous solids: Part I.
AB  - Stabilization of amorphous state is a focal area for formulators to reap benefits
      related with solubility and consequently bioavailability of poorly soluble drugs.
      In the present work, an attempt has been made to explore the potential of moringa
      coagulant as an amorphous state stabilizer by investigating its role in
      stabilization of spray-dried (amorphous) ibuprofen, meloxicam and felodipine.
      Thermal studies like glass forming ability, glass transition temperature, hot
      stage microscopy and DSC were carried out for understanding thermodynamic
      stabilization of drugs. PXRD and dissolution studies were performed to support
      contribution of moringa coagulant. Studies showed that hydrogen bonding and
      electrostatic interactions between drug and moringa coagulant are responsible for
      amorphous state stabilization as explored by ATR-FTIR and molecular docking.
      Especially, H-bonding was found to be predominant mechanism for drug
      stabilization. Therein, arginine (basic amino acid in coagulant) exhibited
      various interactions and played important role in stabilization of aforesaid
      amorphous drugs.

PMID- 22359159
TI  - Enhanced antibacterial effect of ceftriaxone sodium-loaded chitosan nanoparticles
      against intracellular Salmonella typhimurium.
AB  - The aim of the present study was to utilize chitosan (CS) nanoparticles for the
      intracellular delivery of the poorly cell-penetrating antibiotic, ceftriaxone
      sodium (CTX). In vitro characterization of (CTX-CS) nanoparticles was conducted
      leading to an optimized formula that was assessed for its biocompatibility to
      blood (hemolysis test) and cells (MTT assay). Progressively, confocal laser
      scanning microscopy (CLSM), cellular uptake (microfluorimetry), and antibacterial
      activity of the nanoparticles were investigated in two cell lines: Caco-2 and
      macrophages J774.2 pre-infected with Salmonella typhimurium. Results showed that
      the optimized formula had size 210 nm, positive zeta potential (+30 mV) and
      appreciable entrapment efficiency for CTX (45%) and included a biphasic release
      pattern. The nanoparticles were biocompatible and were internalized by cells as
      verified by CLSM whereas microfluorimetry indicated substantial cellular uptake.
      Moreover, the CTX-chitosan nanoparticles showed a significant reduction in the
      count of intracellular S. typhimurium in Caco-2 and macrophages J774.2. This
      reduction was significantly higher than that obtained in case of placebo
      nanoparticles, CTX, and CTX-chitosan solutions and might be attributed to
      enhanced endocytic uptake of the nanoaprticles and antibacterial effect of the
      chitosan polymer. In conclusion, the results provide evidence for the potential
      use of chitosan nanoparticles to enhance the intracellular delivery and
      antibacterial effect of CTX in enterocytes and macrophages.

PMID- 22359160
TI  - The genetic basis of primary aldosteronism.
AB  - Primary aldosteronism is commonly regarded as largely sporadic, but both germline
      and somatic mutations are increasingly recognized as underlying the condition.
      Three germline mutations causing familial hyperaldosteronism have been described,
      dubbed FH I (due to a CYP11B1/CYP11B2 chimera), FH II (localized to chromosome
      7p22, exact location of mutation[s] unknown to date), and FH III (reflecting a
      T158A mutation in the potassium channel subunit KCNJ5). Major contributions (FH
      I, FH III) have been by Lifton and his associates; more recently they have also
      described somatic mutations (G151R, L168R) in KCNJ5 in over a third of
      aldosterone-producing adenomas, with results confirmed, refined, and extended in
      a much larger study from Europe. These findings have sparked considerable
      interest, and over the next 12 months a number of additional reports can be
      confidently expected to throw light on both normal and abnormal adrenocortical
      zonation and the genesis of primary aldosteronism.

PMID- 22359162
TI  - In vitro test system for compounds affecting cholesterol pathway: Studies in
      primary rat liver cell cultures.
AB  - Rat liver cells derived from male and female animals in primary monolayer
      cultures were investigated for suitability as a test system for xenobiotics
      affecting the cholesterol pathway. An appropriate mode of extraction and
      separation of newly formed cholesterol and precursors is described. This system
      can be widely applied.Rat liver cells from females in oestrus cycle had a higher
      synthesis rate of cholesterol than those from males. The disadvantages related to
      the cycle phases make male rats more appropriate donor animals for the test
      system developed. The altered in vitro cholesterol synthesis is relevant to that
      in vivo.The extraction of newly synthesized cholesterol and its precursors by
      means of columns packed with large-pore kieselgur is precise and time saving. The
      modified separation by thin-layer chromatography on silica gel layers impregnated
      with silver nitrate enables direct separation from the extract and is sufficient
      to recognize cholesterol and its precursors.The method in this form is suitable
      for processing a large number of specimens e.g. for screening.

PMID- 22359163
TI  - Dexamethasone regulation of terminal differentiation in 3T3-F442A preadipocyte
      cell line.
AB  - The 3T3-F442A preadipocyte cell line was previously shown to possess specific
      glucocorticoid receptors whose number increased in the time course of
      differentiation. We have examined the effects of a three day dexamethasone
      treatment, added at confluence, on cells differentiated in the presence or
      absence of insulin. Triglyceride accumulation, polyamine content as well as
      glycerophosphate dehydrogenase and fatty acid synthetase activities were measured
      during the adipose conversion. We have also determined 2-deoxyglucose uptake in
      non-differentiated and differentiated cells. Dexamethasone was shown to decrease
      the adipose conversion by 3T3-F442A cells in the presence or absence of insulin.
      Intracellular spermidine content in differentiating cells was sensitive to
      dexamethasone and insulin in the same way as an enzymatic marker of terminal
      differentiation, glycerophosphate dehydrogenase. Dexamethasone decreases the 2
      deoxyglucose uptake in non-differentiated and differentiated cells while insulin
      increases this uptake only in differentiated cells. This work shows that
      glucocorticoids inhibit adipocyte metabolism at distinct levels and suggests that
      these hormones might play an important role in the regulation of adipose tissue
      mass.

PMID- 22359161
TI  - Technology and uses of cell cultures from the tissues and organs of bony fish.
AB  - For a wide range of purposes, primary cell cultures and/or cell lines have been
      prepared from most tissues and organs of a small fraction of the estimated 20,000
      species of bony fish. These cell cultures usually have been maintained with
      mammmalian sera. For many applications their usefulness would be enhanced by a
      more piscine and defined environment. However, the piscine equivalents of
      mammalian polypeptide growth and differentiation factors are largely unknown and
      are unlikely ever to be available commercially. In the future they might be
      obtained from the medium in which fish cells have been grown. Therefore, by being
      a potential source of fish polypeptide growth and differentiation factors, a cell
      line from a fish organ might be utilized as a Rossetta stone to decipher thein
      vitro proliferation and differentiation of other cells from this or other organs
      from the same or different species.

PMID- 22359164
TI  - Immunoglobulin production stimulating and inhibiting factors derived from human
      lung adenocarcinoma PC-8 cells : Ig production stimulating factor in PC-8 cells.
AB  - Addition of a 3 M KCl extract of a human lung adenocarcinoma PC-8 cells to the
      culture media of lymphocytes, which were isolated from normal donors and from
      lung or breast cancer patients, elevated immunoglobulin (Ig) production by 3-5
      times in the presence of pokeweed mitogen. However, addition of higher
      concentration of the extract inhibited Ig production and proliferation of
      lymphocytes. The Ig production stimulating factor (IPSF) was separated from the
      inhibiting factor, using 50% ammonium sulfate precipitation. Upon
      chromatofocusing, IPSF activity was detected mainly in the pH 4.5 fraction but
      minor activity was also detected in other pH fractions. IPSF also enhanced Ig
      production of a B-lymphoblastoid cell line transformed by Epstein-Barr virus and
      a human-human hybridoma, by more than 2-fold. This suggests that IPSF interacts
      with B-lymphocytes directly to enhance their Ig production. IPSF activity was
      also detected diversely in human lung squamous carcinoma QG56, human B
      lymphoblastoid HO-323, and a T cell line CEM.

PMID- 22359165
TI  - Polystyrene substratum for bulk culture of anchorage dependent cells.
AB  - Twisted ribbons made of polystyrene were used as a packing material for the
      cultivation of anchorage dependent cells. Normal human fibroblast cells grown on
      this support in a laboratory scale reactor reached densities of about 5-7*10(5)
      cells/ml. The cells adhered strongly to the carrier and no cell detachment was
      observed upon transfer to serum free medium. The properties of this packing
      material and its potential use are discussed.

PMID- 22359166
TI  - The usefulness of CHAPS as a non-cytotoxic stabilizing agent in purification of
      growth factors.
AB  - Among several detergents, a zwitterionic detergent, 3-[(3
      cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS), was found to be
      least cytotoxic for cultured mammalian cells. CHAPS improved the activity
      recovery and elution profile of crude and purified fibroblast growth factors
      (FGFs) during chromatographies. Diluted preparations of FGFs were stabilized by
      CHAPS against the loss during storage. Amino acid sequence analysis was not
      disturbed by CHAPS. CHAPS was removable by reversed-phase high-performance liquid
      chromatography. These results indicate that CHAPS is useful as a non-cytotoxic
      stabilizing agent in purification of various kinds of bioactive polypeptides.

PMID- 22359167
TI  - Serum-free growth medium for the cultivation of a wide spectrum of mammalian
      cells in stirred bioreactors.
AB  - A serum free medium was developed, that could be used for the large scale
      propagation of various cell lines in bioreactors. The medium is based on a 1:1
      mixture of Iscove's Modified Dulbecco's Medium and Ham's Medium F12, supplemented
      with transferrin, insulin and a BSA/oleic acid complex. Several myelomas,
      hybridomas derived from different myelomas and spleen cells, and other lymphoid
      and non-lymphoid cell lines were cultivated at growth rates comparable to those
      observed using serum-supplemented media. There was furthermore no reduction in
      the formation of products such as monoclonal antibodies or recombinant human
      interleukin-2.

PMID- 22359168
TI  - An immobilized hybridoma culture perfusion system for production of monoclonal
      antibodies.
AB  - A fixed bed perfusion system for hybridoma cell immobilization is presented. The
      system consists of a culturing vessel (300 ml total volume) in which polyurethane
      (PU) sponges in the form of small cubes of about 5 mm sides are packed. Cells are
      immobilized by physical entrapment in the foam matrix. By entrapment of the cells
      in the pores of the matrix high cell concentration can be maintained in a
      mechanically protected environment. Medium is continuously circulated by an
      airlift pump mounted in the cell-free chamber (700 ml total volume).Medium flow
      rate, feeding rate, dissolved oxygen, pH, nutrient uptake and waste product
      formation can be easily monitored and controlled. Steady state conditions are
      established with medium dilution rates of 1.0-1.5 reactor volume per day. The
      steady state is characterized by a constant cell density, constant culture volume
      and constant glucose and lactate levels. Cell-free supernatant is collected
      continuously in a cold room adjacent to the 37 degrees C culture room. Monoclonal
      antibodies (MAb) are produced at a concentration of 150-200 MUg/ml for several
      weeks. An important feature of the system is the capacity to maintain a
      population of cells after the growth phase in a non-proliferating state for
      extended time periods expressing high titers of MAb.

PMID- 22359169
TI  - Fixed bed porous glass sphere (porosphere) bioreactors for animal cells.
AB  - Process intensity of fixed bed glass sphere culture systems is increased
      considerably by replacing solid glass spheres with open pore glass spheres. This
      technique demonstrates the possibility of having a system capable of both
      volumetric and cell density scale up and being suitable for substrate attached
      and suspension cells. The yields achieved for a number of attached cell lines
      (approximately 10(7)/ml) demonstrate an increase approaching one order of
      magnitude over solid glass spheres (approximately 10(6)/ml). Also suspension
      cells were successfully entrapped in the open pore structure with similar yields.

PMID- 22359170
TI  - Purification and characterization of lymphocytic clonal growth factor (LCGF)
      derived from human-human hybridoma SH-76 cells.
AB  - Human-human hybridoma SH-76 cells were found to produce a factor that supported
      the growth of lymphocytic cells at low densities. The factor was purified from
      serum-free conditioned medium of the hybridoma cells by a successive application
      of ammonium sulfate precipitation, DEAE-Toyopearl, TSK G3000 SW and DEAE-5PW
      column chromatograph. The purified factor was a 72K single protein. The factor
      showed marked growth stimulating effect on lymphocytic cell lines, but had no
      effect on the growth of human adhesive cancer cell lines. Thus, the factor is a
      lymphocytic clonal growth factor (LCGF), as found previously in human plasma
      (Miyata, 1988). The LCGF of SH-76 cells could be produced in growth factor-free
      RPMI medium and purified easily from the conditioned medium. The factor is
      inactivated by heating at over 80 degrees C, but is much more stable than the
      LCGF in human plasma.

PMID- 22359171
TI  - The use of ciprofloxacin for the elimination of mycoplasma from naturally
      infected cell lines.
AB  - The fluoroquinolone antibiotic Ciprofloxacin, has been used to eliminate
      mycoplasma from 26 naturally infected cell lines with no evidence of remergence
      of infection and with no treatment failures.

PMID- 22359172
TI  - A new parental cell line for human x human hybridoma production.
AB  - The potential of a new HAT-sensitive human lymphoblastoid cell line TK6 TG(r).P1.
      as a fusion partner was assessed, by comparison with the established human
      parental cell line UC729.6. Both of these cell lines were fused with the
      peripheral blood mononuclear cells of a patient with B-chronic lymphocytic
      leukaemia. The hybridomas generated in these fusion experiments were analysed by
      the fluorescence activated cell sorter and karyotyping. An anti-idiotype ELISA
      assay detected the presence of the patient's characteristic idiotype bearing
      immunoglobulin in the supernatant of a number of the hybridoma cell lines
      generated in both fusions.

PMID- 22359178
TI  - Effect of dialyzate fractions of spinach on growth of human-derived cells.
AB  - Aqueous dialyzate of spinach was separated by Sephadex G-100, G-25 gel
      filtrations and DEAE-cellulose ion exchange chromatography, and the effects of
      the fractions on growth of human-derived normal and cancer cell lines were
      studied. One of the fractions (SPW2) from a Sephadex G-100 gel-filtration of
      dialyzate promoted growth of a hybridoma cell line (HB4C5). Sephadex G-25 gel
      filtration of the SPW2 fraction produced four main fractions; SPW2-1, SPW2-2,
      SPW2-3 and SPW2-4. Among them, the SPW2-1, SPW2-3 and SPW2-4 fractions promoted
      the growth of a histiocytic lymphoma cell line (U-937) and hybridoma cell lines
      (HB4C5 and SI102). Both SPW2-3 and SPW2-4 fractions inhibited the growth of a
      breast cancer cell line (MCF-7). The SPW2-3 fraction, especially, was found to
      inhibit growth of cancer cell lines such as MCF-7, a differentiated hepatoma (HuH
      7), a lung adenocarcinoma (PC-8), a lung squamous carcinoma (QG-56), and a lung
      anaplastic carcinoma (QG-90) more preferentially than that of normal cell lines.
      It was also found that a constituent of the SPW2-3 fraction caused the
      morphological alteration of U-937 cells in serum-free medium.

PMID- 22359179
TI  - Brief report: driving and young adults with ASD: parents' experiences.
AB  - A paucity of research exists regarding driving skills and individuals with Autism
      Spectrum Disorders (ASD). The current study sought to gain a better understanding
      of driving and ASD by surveying parents/caregivers of adolescents/young adults
      with ASD who were currently attempting, or had previously attempted, to learn to
      drive. Respondents included 123 parents/caregivers of adolescents/young adults
      with ASD. The results indicate that learning to drive presents a substantial
      challenge for individuals with ASD; complex driving demands (e.g., multi-tasking)
      may be particularly problematic. Respondents provided suggestions that may be
      useful to others who seek to teach these skills. The survey results offer
      guidance for next steps in the study of driving with ASD.

PMID- 22359180
TI  - On scales of measurement in Autism Spectrum Disorders (ASD) and beyond: where
      Smitty went wrong.
AB  - The author examined critically three beliefs of S.S. Stevens pertaining to his
      quadripartite system of scales of measurement: (1) There are four scales of
      measurement in common usage (2) These scales and the scientific disciplines that
      use them can be incrementally graded for levels of reliability and validity or
      accuracy such that: Nominal scale variables produce the lowest levels of
      reliability and accuracy; with successively improving levels for Ordinal, Equal
      Interval, and Equal Ratio scales; and (3) The scale upon which a variable is
      measured determines the type of statistical test that one is permitted to apply.
      It was shown that each of the three beliefs is fundamentally flawed. 

PMID- 22359182
TI  - The dual role of the context in postpeak performance decrements resulting from
      extended training.
AB  - The context's role in Pavlovian conditioning depends on the trial spacing during
      training, with massed trials revealing a function akin to that of discrete
      stimuli, and spaced trials revealing a modulatory function (Urcelay & Miller,
      Journal of Experimental Psychology. Animal Behavior Processes, 36, 268-280,
      2010). Here we examined the contextual determinants of a common but largely
      ignored effect: attenuated conditioned responding with extended reinforced
      training (i.e., a postpeak performance deficit [PPD]). Contextual sources of PPDs
      were investigated in four fear-conditioning experiments with rats. In Experiment
      1, as the number of reinforced trials increased, conditioned responding
      decreased, even when testing occurred outside the training context. Experiment 2
      revealed opposing influences of context on the PPD based on trial spacing, which
      interacted with whether testing occurred in the training context. This finding
      reconciles Experiment 1's results with previous data (Bouton, Frohardt, Sunsay,
      Waddell, & Morris, Journal of Experimental Psychology. Animal Behavior Processes,
      34, 223-236, 2008). Experiment 3 suggested that extended training with these
      parameters did not lead to habituation to conditioned or unconditioned stimuli.
      In Experiment 4, few or many massed training trials were followed orthogonally by
      context extinction or no context extinction. After many pairings, context
      extinction reduced the PPD (i.e., enhanced responding), suggesting a competitive
      role of the context. These results, together with prior data suggesting that
      context modulates expressions of the PPD, are consistent with the view that
      contexts can play two distinctly different roles.

PMID- 22359183
TI  - General practitioners' perceptions of pharmacists' new services in New Zealand.
AB  - BACKGROUND: In recent years, the pharmacy profession has moved towards more
      patient-oriented services. Some examples are medication review, screening and
      monitoring for disease, and prescribing. The new services are intended to be in
      close collaboration with general practitioners (GPs) yet little is known of how
      GPs in New Zealand perceive these new services. Objective To examine GPs'
      perceptions of pharmacists' new services. SETTING: Study was undertaken at GPs'
      practices in two localities in New Zealand. METHODS: Qualitative, face to face,
      semi-structured interviews were undertaken of 18 GPs. The cohort included GPs
      with less/more than 20 years of practice, and GPs who had experience of working
      in localities where some patients had undergone a medication review (Medicines
      Use Review, MUR) by community pharmacists. GPs were asked to share their
      perceptions about pharmacists providing some new services. Data were thematically
      analysed with constant comparison using NVivo 8 software. Using a business
      strategic planning approach, themes were further analysed and interpreted as the
      services' potential Strengths, Weaknesses, Opportunities and Threats (SWOTs).
      MAIN OUTCOMES MEASURE: GPs' perceptions of pharmacists' new services. RESULTS:
      GPs were more supportive of pharmacists' playing active roles in medication
      review and less supportive of pharmacists practising screening-monitoring and
      prescribing. Discussions Pharmacists' knowledge and skills in medication use and
      the perceived benefits of the services to patients were considered the potential
      strengths of the services. Weaknesses centred around potential patient confusion
      and harm, conflict and irritation to GPs' practice, and the potential to fragment
      patient-care. Opportunities were the possibilities of improving communication,
      and having a close collaboration and integration with GPs' practice. Apparent
      threats were the GPs' perceptions of a related, and not renumerated, increase in
      their workloads, and the perception of limited benefit to patients. CONCLUSION:
      Pharmacists should exploit their own strengths and the potential opportunities
      for these services, and reduce any weaknesses and threats. A possible strategic
      plan should include increased effective communication, piloting services, and the
      integration of some services into medical practices.

PMID- 22359184
TI  - [Evolution of the access to the kidney transplantation in France of foreign
      patients and French patients living in overseas territories].
AB  - In France, foreign patients, whether resident or not in France, can register on
      the national waiting list under administrative and financial conditions. We
      performed a retrospective analysis to evaluate the access to kidney
      transplantation on a cohort 2004-2008, using the national registry. Among the
      14,732 patients registered during this period, 15.3% are of non-French
      nationality (3.4% other European, 5.9% North African, 3.9% sub-Saharan African,
      2.9% other). Among the 84.6% of French nationality, 3.3% are living in French
      overseas territories. Compared to the 17.6-month median waiting time of the
      cohort, median waiting time differs significantly between groups, from 15.7
      months for mainland French patients to 36 months for sub-Saharan African
      patients. Despite the regular development of the allocation rules, these
      disparities in access to transplantation are mainly, but not completely,
      explained by blood group or HLA matching difficulties. After adjustment for the
      other factors known to be significantly linked to a difficult access to
      transplantation, North and sub-Saharan African patients have the worst
      difficulties. Future research should consider nonmedical factors, such as socio
      economic or socio-cultural factors, potentially relevant to avoid disparities in
      access to transplantation and should aim at developing specific interventions.

PMID- 22359185
TI  - [Clinical study of tolerance and effectiveness of a F(ab')(2) polyvalent antienom
      for African snake bites in Kindia, Guinea].
AB  - An open, pragmatic, phase IV clinical trial was undertaken to measure tolerance
      and assess the effectiveness of Antivipmyn(r) Africa, antivenom composed of
      lyophilized F(ab')(2) fragments of immunoglobulin G in field conditions. The
      study was conducted at the Institut Pasteur of Guinea (IPG) from August 2009 to
      February 2010. Two hundred twenty-eight victims of snakebites presented at the
      processing center of the IPG during this period, including one hundred fifty
      (65.8%) envenomations, mostly young men. One hundred twenty-four of them (82.7%)
      suffered from viper envenomations and 26 (17.3%) from elapid ones. All patients
      were treated by intravenous Antivipmyn(r) Africa, averaging 1.4 (+/- 1.0) vials,
      more in patients with neurotoxic envenomation than others (P < 10(-5)). Four
      patients (2.7%), showing cobralike envenomation, died shortly after their arrival
      at the IPG despite the administration of the antivenom. Ten patients showed mild
      side effects (rash or pruritus), out of which 5 (3.3%) were probably due to
      treatment. This study confirms the efficacy and safety of Antivipmyn(r) Africa.

PMID- 22359186
TI  - Proceedings of the IIIrd BELACT meeting Diepenbeek (Hasselt), Belgium March 22,
      1994.

PMID- 22359188
TI  - Simultaneous determination of six active components in traditional herbal
      medicine 'Oyaksungisan' by HPLC-DAD.
AB  - In this study, an effective high performance liquid chromatography-diode array
      detector (HPLC-DAD) method was established for simultaneous determination of six
      marker compounds, ephedrine hydrochloride, 6-gingerol, glycyrrhizin, hesperidin,
      imperatorin and ferulic acid, in a Korean traditional prescription, Oyaksungisan,
      which is used for hemiplegia, arthralgia and paralysis. The six marker compounds
      of Oyaksungisan were separated on a LUNA C18 column (S-5 MUm, 4.6 mm I.D. * 250
      mm) at a column temperature of 35 degrees C. The gradient elution was composed of
      water with 0.1% trifluoroacetic acid and methanol. The detection UV wavelengths
      were set at 207, 250, 280 and 320 nm. Calibration curves for the six compounds
      showed good linear regressions (R (2) > 0.9999). The limits of detection and
      limits of quantification were within the ranges 0.003-0.01 and 0.01-0.04 MUg/ml,
      respectively. The relative standard deviation (RSD) values of intra- and inter
      day testing were within the ranges 0.10-1.82 and 0.04-1.59%, respectively. The
      results of the recovery test were 95.05-104.27% with a RSD value of 0.11-1.85%.
      In conclusion, the simultaneous determination method developed was useful in the
      quality evaluation of Oyaksungisan.

PMID- 22359189
TI  - Evaluation of n-hexane extract of Viola betonicifolia for its
      neuropharmacological properties.
AB  - Viola betonicifolia (whole plant) has been used as a sedative and in various
      nervous disorders in Pakistani traditional medicines. The n-hexane extract of the
      whole plant of V. betonicifolia (HEVB) was investigated for neuropharmacological
      properties such as anxiolytic, muscle relaxant, sleep induction, antidepressant
      and sedative to ascertain its folk use. Anxiolytic activity was tested using the
      staircase test, while the muscle relaxing property of the extract was tested in
      various muscle relaxant paradigms, i.e. chimney test, traction test, rota rod and
      inclined plane. In anxiolytic and muscle relaxant tests, HEVB (0.3, 0.4 and 0.5
      g/kg, i.p.), diazepam (1 mg/kg, i.p.) or distilled water (10 ml/kg i.p.) were
      administered 30, 60 and 90 min before performing the tests in mice. HEVB was also
      screened for a sleep-inducing effect. The antidepressant activity was determined
      by using the forced swimming test (FST), while line crossing in a special box was
      used for locomotor activity. HEVB showed a significant (P < 0.05) dose-dependent
      anxiolytic action in the staircase test. In muscle relaxant paradigms, a dose
      dependent muscle relaxation was observed. For the phenobarbitone sleep induction
      test, HEVB notably (P < 0.05) reduced the latency time and increased the total
      sleeping duration. However, HEVB was devoid of any antidepressant activity, while
      the movements of mice were reduced significantly (P < 0.05) in locomotor
      activity. The results suggest that HEVB has anxiolytic, muscle relaxant, sleep
      inducing (sedative) activity and, thus, provides pharmacological justification
      for the use of this plant as a sedative and for the relief of various nervous
      disorders.

PMID- 22359190
TI  - Volatile profile differences and the associated Sirex noctilio activity in two
      host tree species in the Northeastern United States.
AB  - Sirex noctilio females are known to be attracted to stem sections of stressed
      pine trees for oviposition. The volatile profiles and attractiveness of Eastern
      white pine (Pinus strobus) and two chemotypes of Scots pine (P. sylvestris) were
      compared after stem injection with herbicide. In general, trap captures on
      herbicide-treated trees were higher than on controls. The high-carene chemotype
      of Scots pine captured the highest numbers of females, followed by the low-carene
      chemotype, and finally the Eastern white pine. Herbicide-treated trees of both
      species emitted larger quantities of volatiles than the controls. The herbicide
      treatment induced higher volatile emission rates in the Scots pine chemotypes
      than in white pine, although there was no difference between the two chemotypes.
      However, qualitative differences were found between the volatile profiles of the
      two species as well as between the two Scots pine chemotypes, which could account
      for the differential attractiveness of the species and chemotypes tested.

PMID- 22359191
TI  - Geriatric inflammatory bowel disease: phenotypic presentation, treatment
      patterns, nutritional status, outcomes, and comorbidity.
AB  - BACKGROUND AND AIMS: The U.S. population is aging and the burden of geriatric
      inflammatory bowel disease (IBD) patients has increased. Systematic data
      describing phenotypic presentation, treatment regimens, outcomes and
      comorbidities in elderly IBD patients is limited. We performed a retrospective
      observational study of IBD patients age >=65 followed in a 20-hospital system to
      determine patterns of phenotypic presentation, treatment, polypharmacy,
      nutritional status and comorbidity. METHODS: Data were extracted from electronic
      medical record based on ICD-9 coding/indexed terms on Crohn's disease (CD) and
      ulcerative colitis (UC) patients. RESULTS: A total of 393 geriatric IBD patients
      were identified (49.1% males; 50.9% females; 61.8% UC; 38.2% CD; 73.4 +/- 6.6
      years old). Younger age at diagnosis of CD (<=64) was associated with greater
      prevalence of small bowel surgeries (63.6%) compared with those diagnosed after
      age >=65 (20.9%) (p < 0.005). Fistulizing/penetrating disease was frequent in
      patients diagnosed with CD at a younger age (43.6% compared to 7%) (p < 0.005).
      IBD maintenance treatment included: 44% 5-ASA agents; 31.6% maintenance
      prednisone (defined as >=6 months treatment duration); 4.8% steroid
      suppositories; 5.6% 6MP/azathioprine; 1.3% methotrexate; 1.3% adalimumab; 1.3%
      infliximab; 9.4% loperamide/diphenoxylate/atropine; 0.5% had no IBD medications.
      Longer duration of CD disease correlated with vitamin B12, vitamin D and iron
      deficiency. CONCLUSION: Geriatric patients diagnosed with CD earlier in life had
      greater small bowel involvement compared with new onset geriatric CD. There is
      low utilization of immunomodulator and biologic agents in geriatric IBD patients.
      Duration of CD correlates with nutrient deficiency. Prospective studies are
      warranted in this respect.

PMID- 22359192
TI  - A nanofiber membrane maintains the quiescent phenotype of hepatic stellate cells.
AB  - BACKGROUND: Hepatic stellate cells (HSC) play a major role in the progression of
      liver fibrosis. AIM: The aim of our study was to investigate whether rat HSC
      cultured on a nanofiber membrane (NM) retain their quiescent phenotype during
      both short- and long-term culture and whether activated HSC revert to a quiescent
      form when re-cultured on NM. METHODS: Rat HSC cultured for 1 day on plastic
      plates (PP) were used as quiescent HSC, while cells cultured for 1 week on PP
      were considered to be activated HSC. Quiescent or activated HSC were subsequently
      plated on PP or NM and cultured for an additional 4 days at which time their gene
      expression, stress fiber development, and growth factor production were
      determined. For long-term culture, HSC were grown on NM for 20 days and the cells
      then replated on PP and cultured for another 10 days. RESULTS: Expression of
      marker genes for HSC activation, stress fiber development, and growth factor
      production were significantly lower in both quiescent and activated HSC cultured
      on NM than in those cultured on PP. After long-term culture on NM, activation
      marker gene expression and stress fiber development were still significantly
      lower in HSC than in PP, and HSC still retained the ability to activate when
      replated onto PP. CONCLUSIONS: HSC cultured on NM retained quiescent
      characteristics after both short- and long-term culture while activated HSC
      reverted toward a quiescent state when cultured on NM. Cultures of HSC grown on
      NM are a useful in vitro model to investigate the mechanisms of activation and
      deactivation.

PMID- 22359193
TI  - Transfection of PDCD5 effect on the biological behavior of tumor cells and
      sensitized gastric cancer cells to cisplatin-induced apoptosis.
AB  - BACKGROUND: Programmed cell death 5 (PDCD5) expression is reduced in various
      human tumor cells, and the protein concentration and nuclear translocation of
      PDCD5 is also observed during tumor cell apoptosis. AIMS: The purpose of this
      study was to investigate the differential expression of PDCD5 in six gastric cell
      lines, and to explore the changes of biological behavior mechanism underlying
      enhanced apoptosis-inducing effects of cisplatin by PDCD5 over-expression on
      gastric cancer BGC823 cells. METHODS: RT-PCR and real-time PCR were used to
      determine PDCD5 expression. BGC823/PDCD5 cells were assessed the cellular
      proliferating ability by MTT assay, soft agar cloning experiments and
      tumorigenicity in nude mice experiments in vivo. The effects of cisplatin in
      combination with PDCD5 on the proliferation and apoptosis were measured by MTT,
      Annexin-V-FITC/PI dual labeling and cell cycle analysis, respectively.
      Immunofluorescence was used to detect co-localization of p53 and PDCD5 protein to
      explore the mechanism underlying the synergistic therapeutic effect of PDCD5 with
      cisplatin (5 MUg/ml for 24 h). RESULTS: PDCD5 had the highest expression level in
      the GES1 cell among other cell lines. The growths of BGC823 cells transfected
      with PDCD5 for six (6th) or 17 (17th) days were both slower than that of BGC823
      and BGC823/Neo (P < 0.01). The stable transfection of PDCD5 demonstrated G2/M
      cell cycle arrest, increased apoptosis and nuclear translocation of PDCD5 and p53
      after cisplatin treatment. CONCLUSIONS: Stable transfection of the PDCD5 gene can
      inhibit the growth of the BGC823 cell line and notably improve apoptosis-inducing
      effects of cisplatin, indicating a novel strategy for better chemotherapeutic
      effects on gastric cancer.

PMID- 22359194
TI  - The thrombin inhibitor, argatroban, inhibits breast cancer metastasis to bone.
AB  - BACKGROUND: Breast cancer has the potential to metastasize to bone, causing
      debilitating symptoms. Although many tumor cells have thrombin-generating systems
      originating from tissue factor (TF), therapy in terms of the coagulation system
      is not well established. To elucidate the efficacy of the thrombin inhibitor,
      argatroban, on bone metastasis, we investigated TF activation and vascular
      endothelial growth factor (VEGF) secretion on treatment with thrombin and
      argatroban. METHODS: MDA-231 breast cancer cells were treated with thrombin in
      presence or absence of argatroban, and TF activity was measured in the form of
      activated factor X. Enzyme-linked immunosorbent assay (ELISA) was used to measure
      VEGF concentrations in the medium. MDA-231 cells were injected into the left
      heart ventricle of mice, and then argatroban or saline was administered
      intraperitoneally for 28 days. After 28 days, incidence of bone metastasis was
      evaluated in the limbs by radiography. RESULTS: TF activity and VEGF secretion
      were upregulated by thrombin. Argatroban inhibited the enhancement of TF activity
      and VEGF secretion induced by thrombin. In vivo analysis revealed that the number
      of metastasized limbs in the argatroban group was significantly lower compared
      with the saline group (P < 0.05). CONCLUSIONS: Thrombin not only enhances VEGF
      secretion but also has a positive feedback mechanism to reexpress TF. These
      results indicate that inhibition of thrombin is of great value in suppression of
      tumor metastasis. Argatroban is a noteworthy and useful thrombin inhibitor
      because it has already been used in the clinical setting and has antimetastatic
      effects in vivo.

PMID- 22359195
TI  - Biological characteristics of luminal subtypes in pre- and postmenopausal
      estrogen receptor-positive and HER2-negative breast cancers.
AB  - BACKGROUND: Estrogen receptor (ER)-positive and human epidermal growth factor
      receptor 2 (HER2)-negative breast cancers can be divided into luminal A and
      luminal B subtypes based on Ki67 expression levels. However, the biological
      differences in ER and progesterone receptor (PR) expression levels between these
      luminal subtypes are not clear. METHODS: We examined immunohistochemical
      expression levels of ER, PR, and Ki67 in 180 ER-positive/HER2-negative breast
      cancers while taking menopausal status into account. Breast cancers were divided
      according to ER and PR levels (H: >50%, L: <= 50%), and luminal A and B were
      classified by the Ki67 labeling index (A: Ki67 <14%, B: Ki67 >= 14%). RESULTS:
      When breast cancers were classified based on ER and PR levels, the distribution
      of pre- and postmenopausals was significantly different for luminal A (P <
      0.0001), but not for luminal B cancers. As for luminal A, ER-H/PR-L cancers were
      rare among premenopausals (8%), but frequent among postmenopausals (54%).
      Correlation between ER and PR levels among luminal A cancers was strong in
      premenopausals but weak in postmenopausals. Since crosstalk with growth factor
      signaling is unlikely in luminal A, we speculate that intratumoral estrogen
      insufficiency contributed to the characteristics of postmenopausal ER-H/PR-L
      cancers. CONCLUSION: We speculate that the biological characteristics of luminal
      A cancers are influenced by the estrogen environment, but its influence on
      luminal B cancers may be limited. We believe these considerations constitute
      useful information for a better understanding of the biology of ER-positive-HER2
      negetive breast cancers.

PMID- 22359196
TI  - Heart rate variability in neonates with hypoxic ischemic encephalopathy.
AB  - OBJECTIVE: To evaluate the changes in heart rate variability (HRV) in newborns
      with hypoxic-ischemic encephalopathy (HIE). METHODS: Twenty-two newborns (14
      boys, 8 girls) with moderate or severe HIE and 24 term neonates with similar
      gestational and postnatal age for control were included in this study. Normalized
      low and high frequency components of HRV and their ratio were evaluated for 24-h
      in newborns with HIE and control subjects. RESULTS: The newborns with hypoxic
      ischemic encephalopathy had significantly lower normalized low frequency (LFn)
      and low frequency (LF) / high frequency (HF) values and higher normalized high
      frequency (HFn) values when compared with the control babies. In addition, when
      the cases with severe HIE are compared with those of moderate HIE, decreased LFn,
      LF/HF values and also increased HFn values were present in the severe cases.
      CONCLUSIONS: HIE is associated with reduced sympathetic nervous system activity,
      and increased parasympathetic nervous system activity and these activities also
      correlate with the severity of the disease.

PMID- 22359197
TI  - Retinopathy of Prematurity in a rural Neonatal Intensive Care Unit in South India
      -a prospective study.
AB  - OBJECTIVE: To report the incidence, spectrum and treatment outcome of Retinopathy
      of Prematurity (ROP) in a rural neonatal nursery. METHODS: This Prospective,
      observational, non-randomized study was conducted in a level III Neonatal
      Intensive Care Unit (NICU) at district headquarters in South India. 118 babies
      with birth weight <=2000 g and/or period of gestation (POG) <=34 wk were included
      in the study. Eligible infants were screened with indirect ophthalmoscopy and
      wide-field digital imaging (Retcam) until retinal vascularization was complete or
      disease regressed. Early Treatment Retinopathy of Prematurity (ETROP) guidelines
      were followed for laser. RESULTS: The overall incidence of ROP was 41.5% and
      treatable ROP was 26.4% (24/91) of eyes diagnosed with ROP and 10.2% (24/236) of
      the overall eyes screened. The mean birth weights and periods of gestation with
      and without ROP were 1555.9 vs. 1672.5 g (P 0.005) and 32.2 vs. 34.6 wk,
      respectively (P<0.001). Half of the treated eyes had aggressive posterior ROP in
      Zone 1. All treated eyes had a favorable outcome. Respiratory distress syndrome,
      oxygen therapy, neonatal Jaundice and sepsis were higher in the ROP group but was
      not statistically significant. Of the overall infants screened, 68 (57.6%) were
      heavier and older than the American screening cut-off. Of these, 36.8% had some
      stage ROP and 8% required treatment. CONCLUSIONS: This is the first prospective
      ROP study from a district NICU in India and compares with previously published
      urban data. If Western-screening guidelines are used in the rural scenario, we
      risk a significant proportion of infants being missed who may require treatment.

PMID- 22359198
TI  - Are drug combinations safe in the pediatric practice?

PMID- 22359199
TI  - Human bertiellosis from north India.
AB  - A 4-y-old boy presented with a history of episodes of gripping abdominal pain and
      intermittent shedding of segments of a worm in stool, which used to actively
      change in size and shape. On the basis of measurements of the segments and
      characteristic features of the eggs, the worm was identified as Bertiella
      studeri. The characteristic morphological details of the worm, the pitfalls in
      its identification and the zoonotic potential of this rare cestodal infection are
      discussed here.

PMID- 22359200
TI  - From classical psychodynamics to evidence synthesis: the motif of repression and
      a contemporary understanding of a key mediatory mechanism in psychosis.
AB  - The stress vulnerability model has proven to be a politically important model for
      two reasons. It has provided the framework that defines a temporal and dynamic
      process whereby a person's uniquely determined biopsychosocial vulnerability to
      schizophrenia symptoms interacts with his or her capacity to manage stress and
      the amount and type of stress experienced in such a way that the person
      experiences schizophrenia symptoms. Second, the development of this framework
      promoted the notion of inherited and acquired vulnerability. Implicit was that
      vulnerability was individually determined and that there was a role for
      psychosocial factors in the development/maintenance of schizophrenia symptoms.
      This proved to be a catalyst for the development of studies implicating
      psychosocial factors in the etiology of schizophrenia symptoms. Studies derived
      from cognitive-behavioral theories have proven the most successful in identifying
      thinking patterns, emotional disturbances, and neurocognitive and defensive
      vulnerability factors inherent in the development of schizophrenia symptoms.
      Historically, within the psychoanalytic school there has been debate regarding
      the role of repressive coping mechanisms in schizophrenia development.
      Psychoanalytic theories have always appeared incapable of providing etiologic
      explanations of schizophrenia symptoms, with the possible exception of Melanie
      Klein, than other more salient psychosocial schools. Mechanisms within the
      process of repressive coping are consistent with evidence and mechanisms
      supporting the stress vulnerability models and existing cognitive-behavioral
      theories regarding development of paranoid delusions. These mechanisms are less
      consistent with social cognitive explanations of schizophrenia symptoms.

PMID- 22359201
TI  - Collagen type IV-specific tripeptides for selective adhesion of endothelial and
      smooth muscle cells.
AB  - Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs)
      in blood vessels is critically important to minimize the risk associated with
      vascular implants. Extracellular matrix (ECM) plays a key role in controlling the
      cellular balance, suggesting a promising source of cell-selective peptides. To
      obtain EC- or SMC-selective peptides, we start by highlighting sequence
      differences found among ECM molecules as enriched targets for cell-selective
      peptides. We explored the EC- or SMC-selective performance of tripeptides that
      are specifically enriched only in collagen type IV, but not in types I, II, III,
      and V. Collagen type IV was chosen since it is the major ECM in the basement
      membrane of blood vessels, which separates ECs and SMCs. Among 114 collagen type
      IV-derived tripeptides pre-screened from in silico analysis, 22 peptides (19%)
      were found to promote cell-selective adhesion, as determined by peptide array.
      One of the best performing EC-selective peptides (Cys-Ala-Gly (CAG)) was mixed
      into an electrospun fine-fiber, a vascular graft material, for practical
      application. Compared to unmodified fiber, the CAG containing fiber surface was
      found to enhance adhesion of ECs (+190%) while limiting SMCs (-20%). These
      results are not only consistent with the hypothesis of ECM as a source of cell
      selective peptides, but also suggest a new genre of EC- or SMC-selective peptides
      for tissue engineering applications. Collectively, these findings favorably
      support the screening approach used to discover new peptides for these purposes.

PMID- 22359202
TI  - Quantitative assessment of the associations between CYP1A1 polymorphisms and
      gastric cancer risk.
AB  - A great number of studies regarding the association between MspI and Ile462Val
      polymorphisms in the CYP1A1 gene and gastric cancer have been published. However,
      the results have been inconsistent. In this study, a meta-analysis was performed
      to investigate the associations. Published literature from PubMed, ISI Web of
      Science and other Chinese databases were searched for eligible publications.
      Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated
      using random or fixed effect model. Nine studies (860 cases/2183 controls) for
      CYP1A1 MspI polymorphism and nine studies (1161 cases/3273 controls) for CYP1A1
      Ile462Val polymorphism were included in this meta-analysis. MspI polymorphism was
      not associated with gastric cancer risk (dominant model, OR = 0.95, 95%CI 0.80
      1.14; recessive model, OR = 1.01, 95%CI 0.76-1.35; CC vs. TT, OR = 1.03, 95%CI
      0.76-1.41; TC vs. TT, OR = 0.95, 95%CI 0.78-1.15). Similarly, there was no
      association between Ile462Val polymorphism and gastric cancer risk (dominant
      model, OR = 0.93, 95%CI 0.79-1.10; recessive model, OR = 1.34, 95%CI 0.90-2.00;
      GG vs. AA, OR = 1.27, 95%CI 0.84-1.90; AG vs. AA, OR = 0.87, 95%CI 0.71-1.07). In
      the subgroup analysis, no significant association was found in ever smokers,
      never smokers, Asians and Caucasians. This meta-analysis suggested that there
      were no associations between CYP1A1 polymorphisms and gastric cancer.

PMID- 22359203
TI  - Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long
      term follow-up.
AB  - BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare kind of
      cancer. METHODS: In this study, the authors evaluated 52 patients with pulmonary
      LELC who had long-term follow-up. Clinical characteristics, tumor markers,
      epidermal growth factor receptor (EGFR) mutation status, treatments, and outcomes
      were analyzed. RESULTS: Pulmonary LELC mostly affected young, nonsmoking
      patients. Most patients were in early or locally advanced stages and received
      multimodality treatment. Serum levels of neuron-specific enolase and cytokeratin
      19 fragment 21-1 were elevated in 11 of 20 patients and 10 of 16 patients,
      respectively. Mutational analysis of EGFR was done in 11 patients, and all were
      wild type. The median overall survival (OS) for all the patients was not reached,
      and the 2-year and 5-year OS rate was 88% and 62%, respectively. The patients
      with early tumor stage, normal serum lactate dehydrogenase level, normal serum
      albumin level, without lymph node metastasis, and those who underwent complete
      resection had significantly better OS (P < .05); and the serum albumin level was
      an independent prognostic factor in a Cox regression model (P = .005). For all
      patients who underwent complete resection, whether or not they received adjuvant
      chemotherapy did not affect OS (P > .05); whereas, for patients with stage IIIA
      disease who underwent complete resection, adjuvant chemotherapy was correlated
      with a significantly better prognosis (P < .05). CONCLUSIONS: Pulmonary LELC
      obviously is a distinct entity of lung cancer that has a better prognosis,
      because patients with LELC can receive multimodality treatment, and LELC has
      biologic behavior similar to that of nasopharyngeal carcinoma. The current
      results indicated that future collaborative efforts are needed to determine the
      optimal treatment methods for this uncommon malignancy.

PMID- 22359204
TI  - Apoptosis in CHO cell batch cultures: examination by flow cytometry.
AB  - Chinese hamster ovary cells grown under conditions which are optimal for the
      production of a genetically engineered protein in batch culture, lose significant
      viability shortly after entering the stationary phase. This cell death was
      investigated morphologically and was found to be almost exclusively via apoptosi.
      Furthermore, cells were analyzed by flow cytometry using a fluorescent DNA end
      labeling assay to label apoptotic cells, in conjunction with cell cycle analysis
      using propidium iodide. Apoptotic cells could be detected by this method, and by
      the radioactive end-labeling of extracted DNA, on all days of culture from day 1
      to day 7; however, the degree of apoptotic cell death increased dramatically when
      the cells entered the stationary phase, rising to 50-60% of the total cell number
      at the termination of the culture. Flow cytometric analysis showed that the
      majority of cells underwent apoptosis whilst in G(1)/G(0) and formed an apoptotic
      population with high DNA FITC end-labeling and hypodiploid propidium iodide
      binding. Additionally, the ability or inability to secrete specific protein
      products did not appear to interfere with the development of the apoptotic
      population with time.

PMID- 22359205
TI  - Expression of FSH in CHO cells. II. Stimulation of hFSH expression levels by
      defined medium supplements.
AB  - A Chinese Hamster Ovary (CHO-K1) derived cell line, which expresses human
      follicle stimulating hormone (hFSH) under the control of a beta actin promoter,
      was used as a model system to study heterologous glycoprotein expression. It has
      been shown previously that specific productivities in this cell line were three
      times higher in the presence of serum than in its absence. In this paper, a
      systematic study was made of the affects of various serum components of product
      levels in order to determine if the affect of serum on FSH expression could be
      duplicated by defined medium supplements. Culture media were supplemented with
      growth factors, direct activators of secondary messengers, steroids, lipids and
      various sugars. It was shown that the components with the most stimulatory affect
      of hFSH expression were sodium butyrate, mevalonate and hydrocortisone. Although
      butyrate has been shown to elevate transcription of some genes, it was concluded
      that this could not have been the only mechanism of action, since mevalonate and
      hydrocortisone are both implicated in the lipid pathway of protein glycosylation,
      but not with transcriptional activation of the beta actin promoter. Conversely,
      actual supply of dolichol-linked oligosaccharide for glycosylation was probably
      not rate limiting, since butyrate has never been reported to affect the supply of
      this comerabolite, but glycosylation is likely to be implicated in some way.

PMID- 22359206
TI  - Strong buffering capacity of insect cells. Implications for the baculovirus
      expression system.
AB  - Insect cells are widely used for expression of a variety of different proteins by
      using the baculovirus expression system. The applicability of this system depends
      on production of proteins which have biological properties similar to their
      native counterparts. One application has been the expression of viral capsid
      proteins and their assembly into empty capsid structures to provide new viral
      immunogens which retain complex antigenic sites. An important parameter for
      efficient folding and assembly of proteins into viral procapsids may be the
      intracellular pH, particularly for acid-labile particles such as foot-and-mouth
      disease virus (FMDV). Benzoic acid was used as an effective indicator of
      intracellular pH in insect cells and 3-O-methyl glucose to measure cell volumes.
      We have determined the intracellular volume of theSpodoptera frugiperda IPLB-Sf21
      insect cells 0.50+/-0.08 pL per cell. Using the distribution of [(14)C]-benzoic
      acid, we show that the intracellular pH remains constant at pH 7.0 when the cells
      are grown in media with pH values ranging from 6.2 to 6.8 and, moreover, is not
      affected by baculovirus infection. These results suggest that insect cells are
      suitable to express and produce acid-labile structures via the baculovirus
      expression system and that assembly of proteins and viral procapsids could occur.

PMID- 22359207
TI  - The methylene blue colorimetric microassay for determining cell line response to
      growth factors.
AB  - The validity of the methylene blue colorimetric microassay for determining the
      response of monolayers of human ovarian tumour cell lines to different growth
      factors was investigated. Linearity of the relationship between cell density and
      optical density was confirmed for each cell line (r=0.989-0.999,p<0.001), and
      when initial cell density was optimised to give exponential growth over the assay
      period, differences in response to medium supplements were obvious. The response
      of target cells to growth factors, obtained using the methylene blue assay, were
      compared with, and found to parallel, previously documented responses obtained
      non-colorimetrically. Thus Mink lung epithelial cells (MLEC) were inhibited by
      TGbeta (Holleyet al., 1983), EGF had an inhibitory effect on A431 cells (Gill &
      Lazar, 1981; Barnes, 1982), and the mesothelial cell line showed a proliferative
      response to EGF and hydrocortisone (Connell and Rheinwald, 1983).The methylene
      blue colorimetric microssay was found to be a simple, reliable, sensitive method
      with low variability, for determining the response of cultured cells to growth
      factors.

PMID- 22359208
TI  - Changes in metabolism and hormone trafficking during exposure of endocrine cells
      to elevated ammonium.
AB  - Endocrine cell cultures have potential in bioprocessing, for the production of
      biologically active hormones, and in tissue engineering, for the development of
      implantable artificial tissues for long-term restoration of endocrine function.
      To optimize such systems, it is necessary to develop a thorough understanding of
      how inherently present environmental stresses, such as nutrient depletion and
      metabolite accumulation, affect the cells. This work focuses on the effects of
      the metabolite ammonium on indicators of endocrine cell metabolism and on the
      processing, storage and secretion of regulated secretory proteins. Experiments
      were conducted on recombinant insulin-producing mouse pituitary AtT-20 cells and
      mouse insulinoma betaTC3 cells. Exposure for 24-48 hours to 6 mM of exogenous
      ammonium resulted in higher rates of glucose consumption by both AtT-20 and
      betaTC3 cells, while the formation of additional ammonium generally decreased
      relative to ammonium-free controls. When betaTC3 cells were discharged of their
      intracellular insulin stores, the presence of ammonium during a subsequent
      recharge completely inhibited addition of new insulin-related peptides to the
      stores, as we had observed previously for both cell lines. There was a
      correlation between insulin-related peptides stored in betaTC3 cells during
      recharging and the amount that could be released upon secretagogue stimulation.
      Using a combination of radioimmunoassay and high performance liquid
      chromatography, we found that intracellular insulin and insulin-related peptides
      changed in the same fashion. Intracellular mechanisms that may be producing the
      observed results are discussed.

PMID- 22359209
TI  - A specific microassay for evaluating hepatic LDH activity in co-cultures of
      hepatocytes with other cells.
AB  - This study describes the development of a simple, rapid and reproducible
      microassay for determining the intracellular LDH activity of rat hepatocytes
      present in a co-culture system with other cells. The procedure involves treatment
      of cellular homogenates with an anti-LDH antiserum that specifically inhibits the
      LDH activity of rat hepatocytes. The assay is performed in 96-well plates and LDH
      activity can be measured directly in the same wells using a colorimetric method.
      The difference in LDH activity values measured before and after antiserum
      incubation reflects the LDH content of the hepatocytes in the sample. The
      advantages of this method are the small number of cells required, a reduction in
      sample handling and the possibility of differentiating LDH activity in hepatic
      and non-hepatic cells. The possible applications of this technique as a parameter
      for biochemical data and as a test for cytotoxicity studies in co-cultures are
      also discussed.

PMID- 22359210
TI  - Production of immunoglobulin A in different reactor configurations.
AB  - A murine hybridoma line (Zac3), secreting an IgA monoclonal antibody, was
      cultivated in different systems: a BALB/c mouse, a T-flask, a stirred-tank
      bioreactor and a hollow fiber reactor. These systems were characterized in terms
      of cell metabolism and performances for IgA production. Cultures in T-flask and
      batch bioreactor were found to be glutamine-limited. Ammonia and lactate were
      produced in significant amounts. IgA productivity was found to be constant and
      growth associated. Final IgA concentration was similar in both systems. In fed
      batch cultures, supplemented with glutamine and glucose, maximum viable cell
      concentration was increased by 60% and final IgA concentration by 155%. The
      hollow fiber reactor was able to produce very large amounts of IgA at very high
      concentrations, similar to the value found in ascites fluid. The productivity
      ofZac3 is similar to the values reported for IgG-producing cell lines.

PMID- 22359211
TI  - Comparison of the cytotoxic and inflammatory responses of titanium particles with
      different methods for endotoxin removal in RAW264.7 macrophages.
AB  - It is generally accepted that periprosthetic bone resorption is initiated through
      aseptic inflammation aggravated by wear particles that are generated from
      artificial joint. However, some studies have demonstrated that "endotoxin-free"
      wear particles are almost completely unable to stimulate the macrophage-mediated
      production of proinflammatory cytokines. Here, we compare the titanium particles
      with different methods of endotoxin removal. The results indicated that different
      titanium particle preparation dosages did not significantly change particle size,
      morphology, and chemical composition. But it could cause variations in the
      endotoxin concentration of titanium particles and inflammatory responses in
      RAW264.7 macrophages. The particles with higher endotoxin levels correlated with
      more extensive inflammatory responses. When testing endotoxins using the
      supernatant of particle suspensions, it would lead to false negative results
      compared with testing the particle themselves. And when using the particles
      themselves, all the particles should be removed by centrifugation to avoid
      particle interference before the absorbance value was determined. Therefore, we
      suggest that research concerning wear particles should completely describe the
      endotoxin testing process, including endotoxin removal from particles and the
      details of endotoxin testing. Moreover, future research should focus on the
      surface of wear particles (the potential role of adherent endotoxin) rather than
      the particles themselves.

PMID- 22359212
TI  - In vitro study of role of trace amount of Cu release from Cu-bearing stainless
      steel targeting for reduction of in-stent restenosis.
AB  - A novel 316L type Cu-bearing stainless steel was developed in present work,
      aiming at reducing the occurrence of the in-stent restenosis after implantations
      of coronary stents, through trace amount of Cu release from surface of the steel
      in body fluid. It was found that there was a trace amount of Cu released from the
      Cu-bearing steel in a simulated body fluid, with no cytotoxicity. All the in
      vitro experimental results proved that this Cu-bearing steel could not only
      inhibit the proliferation of vascular smooth muscle cells, reducing the formation
      of thrombosis, which are the main reasons for happening of the in-stent
      restenosis, but also promote the proliferation of vascular endothelial cells
      needed for the revascularization, showing that this novel steel is prospective to
      be a new material for manufacturing coronary stents with function of reducing the
      in-stent restenosis.

PMID- 22359213
TI  - New PMMA-based composites for preparing spacer devices in prosthetic infections.
AB  - Even though the systemic antibiotic therapy is usually applied after prosthetic
      infections surgical treatments, it is unable to reach the infection site in
      sufficient concentrations to eradicate bacteria. Delivering antibiotics locally
      with the use of custom made device (spacer or nail coating) might eradicate or
      reduce the infection and the risk of recolonization, providing a very high
      concentration of antibiotic. PMMA-based (Mendec Spine) composites with BaSO(4)
      were enriched with beta-tricalcium phosphate (Porosectan-TCP) or only a slightly
      higher BaSO(4) concentration (Porosectan-BaSO(4)) to obtain higher porosity. The
      aim of the study was to evaluate: (i) drug absorption capability and drug release
      kinetics in vitro soaking them with a combined solution of gentamicin and
      vancomycin, (ii) their in vitro and in vivo biocompatibility, and finally, (iii)
      they were tested preliminarily in an experimental model of bone infection. The
      simultaneous presence of beta-TCP and BaSO(4) resulted in the formation of a
      texture of interconnecting channels with different diameters, from a few microns
      to several hundred microns, which totally filled the material. The porosity,
      determined by microcomputed tomography, was significantly higher in both tested
      plain composites (Porosectan-TCP: +17.3%; Porosectan-BaSO(4): +7.5%) in
      comparison to control composite material (Mendec Spine). The kinetics of
      antibiotic release from composites was rapid and complete, producing high drug
      concentrations for a short period of time. Both composites showed a good level of
      biocompatibility. The osteomyelitic model confirmed that both composites, soaked
      in antibiotic solution, were able to cure bone infection. These composites could
      be useful for preparing devices for prosthetic joint infections treatment also
      allowing the use of antibiotics solution at required concentrations.

PMID- 22359214
TI  - Characterization of a neutral pectin lyase produced by Oidiodendron echinulatum
      MTCC 1356 in solid state fermentation.
AB  - A neutral pectin lyase produced by a new fungal strain Oidiodendron echinulatum
      MTCC 1356 under solid state fermentation using wheat bran as agro waste has been
      studied. The enzyme was purified by ammonium sulphate precipitation (30-60%),
      DEAE anion exchange and Sephadex G-100 column chromatographies. The SDS-PAGE and
      native PAGE revealed two bands of sizes 42 and 47 kDa. The enzyme was purified 37
      fold with specific activity of 4.5 U/mg and 2.25% yield. The K(m) and V(max)
      values determined using citrus pectin were 1.2 mg/ml and 0.36 IU/min
      respectively. The pH and temperature optima were pH 7.0 and 50  degrees C,
      respectively. The pH stability was around 5.0 for 24 h at 20  degrees C. The
      purified enzyme retained maximum activity for 30 min upto 50  degrees C. The
      activation energy for thermal denaturation of the purified enzyme was found to be
      60.0 kJ/Mol. The effects of various metal ions and protein inhibitors on enzyme
      activity have revealed total inhibition of the enzyme activity in the presence of
      Ag(+) and Cu(+) and KMnO(4) at 1 mM. The neutral pectin lyase showed retting of
      Crotalaria juncea fibre in the presence of EDTA.

PMID- 22359215
TI  - O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation and low
      MGMT-encoded protein expression as prognostic markers in glioblastoma patients
      treated with biodegradable carmustine wafer implants after initial surgery
      followed by radiotherapy with concomitant and adjuvant temozolomide.
AB  - BACKGROUND: O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation
      status was proposed as a prognostic biomarker for patients with glioblastoma.
      However, the prognostic impact of MGMT in patients with newly diagnosed
      glioblastoma who receive carmustine-releasing wafers (Gliadel) along with
      temozolomide (TMZ) is still unknown. METHODS: MGMT promoter methylation status
      and protein expression were analyzed in formalin-fixed, paraffin-embedded tumor
      specimens obtained from 111 French patients with newly diagnosed glioblastoma.
      Patients received the Gliadel wafers followed by radiotherapy plus concomitant
      and adjuvant TMZ chemotherapy while they were enrolled in a French multicenter
      prospective study. RESULTS: For the whole cohort, the median overall survival
      (OS) was 17.5 months, and the progression-free survival was 10.3 months. Patients
      with tumors that harbored MGMT methylation had a significantly longer OS compared
      with patients who had wild-type MGMT (21.7 months vs 15.1 months; P = .025).
      Similarly, patients who had low MGMT protein expression (<=15%) had a
      significantly improved OS compared with patients who had high MGMT expression
      (27.0 months vs 15.1 months; P = .021). The extent of resection was the strongest
      clinical predictor of outcome. In multivariate Cox models that were adjusted for
      sex, performance status, and extent of surgery, both MGMT methylation and protein
      expression were identified as independent prognosticators, and the finding was
      validated internally using a bootstrap resampling technique. Discrepancies were
      identified between protein expression and MGMT methylation status, thus
      suggesting that the 2 assays probably assess different biologic features.
      CONCLUSIONS: MGMT promoter methylation status and low MGMT expression both were
      identified as positive prognosticators in patients with newly diagnosed
      glioblastoma who underwent surgical resection and received Gliadel wafer implants
      followed by adjuvant radiotherapy and concomitant oral TMZ chemotherapy (the
      Stupp protocol).

PMID- 22359216
TI  - Potential mucolytic agents for mucinous ascites from pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei is a disease characterised by the accumulation of mucinous
      ascites. Thus far, cytoreductive surgery combined with hyperthermic
      intraperitoneal chemotherapy (HIPEC) has been shown to be effective at
      eradicating disease. Chemotherapy has been less effective, providing disease
      stabilization but not demonstrating significant treatment responses. Mucolytic is
      a potential class of drug that may be exploited in the chemical management of
      this disease. A variety of potential mucolytic agents are explored in this review
      providing evidence of basic biochemical evidence of its efficacy with potential
      translational application.

PMID- 22359218
TI  - Assessment of mineral phosphate-solubilizing properties and molecular
      characterization of zinc-tolerant bacteria.
AB  - Plant growth-promoting bacteria with the ability to tolerate heavy metals have
      importance both in sustainable agriculture and phytoremediation. The present
      study reports on the isolation and characterization of mineral phosphate
      solubilizing (MPS) bacteria associated with the Achyranthes aspera L. plant
      (prickly chaff, flower plant). Out of 35 bacterial isolates, 6 isolates, namely
      RS7, RP23, EPR1, RS5, RP11 and RP19, with high MPS activity were selected and
      subjected to the assessment of MPS activity under various stress conditions, viz.
      ZnSO(4) (0.30-1.5 M), NaCl and temperature. MPS activity by the selected isolates
      was observed at concentrations of as high as >1.2 M ZnSO(4). Significant
      improvement in plant growth was observed on bacterization of seeds (pearl millet)
      with all of the six selected isolates. Plant growth was measured in terms of root
      length, shoot length, fresh weight and % increase in root biomass. The molecular
      diversity among the phosphate-solubilizing bacteria was studied employing
      enterobacterial repetitive intergenic sequence-PCR (ERIC-PCR). Representative
      strains from each ERIC type were identified, on the basis of a partial sequence
      of the 16S rRNA gene, as members of the genera Pseudomonas, Citrobacter,
      Acinetobacter, Serratia, and Enterobacter. Among all the isolates, RP19 was the
      best in terms of phosphate-solubizing activity and its response to various
      stresses. The ability of RP19 and other isolates to exhibit MPS activity at high
      ZnSO(4) concentrations suggests their potential as efficient biofertilizer for
      growing plants in metal (ZnSO(4))-contaminated soil.

PMID- 22359217
TI  - Screening of drugs to counteract human papillomavirus 16 E6 repression of E
      cadherin expression.
AB  - Persistent infections with certain high-risk human papillomavirus (HPV) types
      such as 16 and 18 can result in the development of cervical cancer. Neither of
      the two prophylactic vaccines against HPV16 and 18 that are in current use have
      any therapeutic efficacy for prevalent HPV infections. Ablative therapy is widely
      used for the treatment of HPV cervical dysplasia however disease recurrence is a
      widely recognized problem. Thus there is a continuing need for therapeutic
      approaches for the treatment of HPV infections. The HPV16 E6 viral oncoprotein
      represses surface expression of the cellular adhesion molecule, E-cadherin.
      Reduced E-cadherin expression on HPV-infected keratinocytes is associated with
      lowered numbers of antigen-presenting Langerhans cells in the infected epidermis,
      potentially reducing immune surveillance for HPV. Four chemicals reported to up
      regulate E-cadherin were screened for their ability to counteract E6 repression
      of surface E-cadherin. 5-Aza-2'-deoxycytidine (AzaDC), a DNA methyltransferase
      inhibitor, and Indole-3-carbinol (I3C), reported to increase E-cadherin through a
      p21(Waf1/Cip1)-dependent mechanism, had low cytotoxicity and increased or
      restored E-cadherin expression and adhesive function in HPV16 E6 expressing
      HCT116 cells. Doxorubicin, also known to induce p21(Waf1/Cip1), increased E
      cadherin in E6 expressing cells but had some associated cytotoxicity. Tamoxifen,
      which can restore adhesive function of surface E-cadherin, was ineffective in
      counteracting E6 repression of E-cadherin. AzaDC and I3C both show potential to
      restore antigen-presenting cells to HPV infected skin by antagonizing E6
      repression of E-cadherin, thereby counteracting an important immune evasion
      mechanism of HPV16 and reinstating immune function at the infected site.

PMID- 22359219
TI  - Antibiotics production by an actinomycete isolated from the termite gut.
AB  - As well as the search for new antibiotics, a new resource or strains for the
      known antibiotics is also important. Microbial symbionts in the gut of termites
      could be regarded as one of the feasible resource for such purpose. In this
      study, antibiotic-producing actinomycetes were screened from symbionts of the
      termite gut. 16SrRNA sequence analysis for the 10 isolates revealed that they
      belong to actinomycetes such as Streptomyces sp., Kitasatospora sp., and
      Mycobacterium sp. A culture broth from one of the isolate, namely strain CA1,
      belonging to the genera Streptomyces exhibited antagonistic activity against
      actinomycetes (Micrococcus spp.), gram-positive bacteria (Bacillus spp.), and
      yeast (Candida spp.). The structures of 2 compounds isolated from the culture
      broth of the strain CA1 were identified as those of actinomycin X2 and its
      analog, D. This study is the first to report that some symbionts of the termite
      gut are antibiotic-producing actinomycetes, and suggest that the termite gut is a
      feasible resource for bioprospecting.

PMID- 22359220
TI  - Contingency blindness: location-identity binding mismatches obscure awareness of
      spatial contingencies and produce profound interference in visual working memory.
AB  - The purpose of the present study was to highlight the role of location-identity
      binding mismatches in obscuring explicit awareness of a strong contingency. In a
      spatial-priming procedure, we introduced a high likelihood of location-repeat
      trials. Experiments 1, 2a, and 2b demonstrated that participants' explicit
      awareness of this contingency was heavily influenced by the local match in
      location-identity bindings. In Experiment 3, we sought to determine why location
      identity binding mismatches produce such low levels of contingency awareness. Our
      results suggest that binding mismatches can interfere substantially with visual
      memory performance. We attribute the low levels of contingency awareness to
      participants' inability to remember the critical location-identity binding in the
      prime on a trial-to-trial basis. These results imply a close interplay between
      object files and visual working memory.

PMID- 22359221
TI  - The roles of RGD and grooved topography in the adhesion, morphology, and
      differentiation of C2C12 skeletal myoblasts.
AB  - Both chemical and topographic cues are crucial for the development of skeletal
      muscle. In this study, the relative roles of both signals in regard to cell
      adhesion, morphology, and differentiation of C2C12 skeletal myoblasts were
      investigated. Grooved polystyrene substrates containing grooves with
      approximately 900 nm in width with 600 nm ridge spans and 665 nm in depth were
      conjugated with the cell adhesion peptide arginine-glycine-aspartic acid (RGD).
      RGD conjugation significantly enhanced the adhesion, growth and differentiation
      of C2C12 cells. On the other hand, anisotropic topography primarily directed the
      direction and alignment of myoblasts and myotubes. The results in this study
      provide information regarding the relative roles of chemical and topographic cues
      in musculoskeletal myogenesis, and are of interest to applications in muscle
      tissue engineering.

PMID- 22359222
TI  - Increased FDG uptake in breast cancer is associated with prognostic factors.
AB  - PURPOSE: To evaluate the relationship between FDG uptake and prognostic factors
      of breast cancer such as hormone receptors (estrogen and progesterone),
      expression of c-erbB-2, axillary lymph node status, tumor histology, grade and
      size. MATERIALS AND METHODS: Between May 2009 and February 2011; 79 patients
      (mean age +/- SD: 52.9 +/- 13.9 years) with biopsy proven breast cancer underwent
      F-18 FDG PET/CT scanning for staging. Patients with excisional biopsy or
      neoadjuvant chemotherapy were excluded from the study. Histological types
      included were invasive ductal carcinoma (n = 68), invasive lobular carcinoma (n =
      2), and invasive ductal plus lobular mixed carcinoma (n = 9). Maximum
      standardized uptake values (SUVmax) were compared with estrogen (ER) and
      progesterone receptors (PR), expression of c-erbB-2, as well as tumor grade and
      tumor size. For the evaluation of relationship between tumor SUVmax values and
      prognosticators such as hormone receptors, tumor histologic grade, and tumor
      size, statistical analyses were performed using Student t test, Mann-Whitney U
      Test and Pearson correlation coefficient and p values of less than 0.05 were
      considered to indicate statistically significant differences. RESULTS: All
      primary breast neoplasms were detected by PET/CT scanner. The mean SUVmax values
      and breast cancer tumor sizes ranged from 2.09 to 39.0 and 0.7 to 10 cm,
      respectively. Tumors with negative ER [(n = 19); SUVmax median (min-max): 15
      (2.09-39.0)] were associated with higher SUVmax values (p = 0.01). Tumors with
      overexpression of C-erbB-2 [(n = 28); SUVmax median (min-max): 16.0 (5.0-39.0)];
      tumor grade 3 [(n = 25); SUVmax median (min-max): 15 (6.43-39)]; axillary lymph
      node involvement [(n = 60); SUVmax median (min-max): 13.61 (4.0-39.0)]; tumor
      histopathology and increased tumor size were associated with higher maximum
      standardized uptake values. However, PR did not show any relationship with SUVmax
      values. CONCLUSION: In the present report, strong relationships were detected
      between the negativity of ER, overexpression of c-erbB-2, tumor grade, tumor
      size, histopathology, axillary lymph node involvement and SUVmax values.
      Accordingly, we believe that SUVmax values obtained with (18)F-FDG PET/CT may
      provide some information about tumor biology of breast cancer.

PMID- 22359223
TI  - Simultaneous PET/MR body imaging in rats: initial experiences with an integrated
      PET/MRI scanner.
AB  - OBJECTIVE: We recently developed an integrated positron emission tomography
      (PET)/magnetic resonance imaging (MRI) (iPET/MRI) scanner for small animals,
      which had relatively large field-of-view (FOV) covering up to the size of a rat
      body. The purpose of this study was to report results of simultaneous PET/MRI of
      a rat body using this scanner with some radiotracers. METHODS: C-11-methionine
      (MET), F-18-fluorodeoxyglucose (FDG), or F-18-sodium fluoride (NaF) was injected
      as a radiotracer for PET portion in addition to gadolinium-ethoxybenzyl
      diethylenetriamine penta-acetic acid, a hepatobiliary contrast agent, for MRI
      portion. Simultaneous PET/MRI was performed in normal rats. PET, MRI, and co
      registered fusion images were evaluated regarding image quality and feasibility
      for rat imaging studies. RESULTS: MET uptake was clearly shown in the liver and
      pancreas, which was confirmed with magnetic resonance (MR) and fused PET/MR
      images. PET/MR images depicted intense FDG uptake in the brain, Harderian glands,
      and myocardium. NaF uptake was observed in all bones and joints within FOV,
      except in ribs, which was well recognized with the help of MR and fused PET/MR
      images. CONCLUSION: This study demonstrated that simultaneous PET/MRI with an
      integrated dual-modality molecular imaging scanner was a feasible technique for
      imaging studies targeting on a rat body. However, further developments including
      attenuation correction methods are required to use this technique routinely in
      rat imaging studies.

PMID- 22359224
TI  - CT tube current for attenuation map in a combined PET/CT system: obese patient
      simulated phantom study.
AB  - OBJECTIVE: The CT portion of PET/CT provides attenuation correction of the PET
      emission scan. This study was performed to evaluate how much the CT tube current
      can be lowered while still providing attenuation maps on PET images. METHODS: Two
      body phantoms (outside diameters of 300 and 500 mm) were used to investigate, and
      PET/CT acquisitions were performed with an Aquiduo PCA-7000B (Toshiba Medical
      Systems, Otawara, Japan). The CT scan was performed with the following parameters
      (120 kVp; 0.5-s rotation; 10, 20, 40, 80, 160, 200, 320, 460 mA). After the CT
      scan, PET images for (18)F-FDG (5.3 kBq/mL) were obtained for 4 min/bed position.
      The linear attenuation coefficients for (18)F-FDG in 300- and 500-mm phantoms,
      pixel values and SD of CT images, radioactivity concentration values and hot- and
      cold-sphere contrast on PET images in the 500-mm phantom were evaluated. RESULTS:
      In the 300-mm phantom, all eight tube currents gave average linear attenuation
      coefficients of approximately 0.095 cm(-1). In contrast, the average linear
      attenuation coefficients of the 500-mm phantom at 10, 20, and 40 mA were
      significantly decreased (0.081, 0.087, and 0.092 cm(-1), respectively; p < 0.05)
      as compared to 0.096 cm(-1) of the other tube currents. Further, CT pixel values
      decreased 10 and 20 mA. Thus, the background radioactivity concentration values
      at 10 and 20 mA were substantially underestimated to be 57 and 80%, respectively
      (p < 0.05); the hot-sphere contrast values at 10 and 20 mA were 0.26 and 0.29;
      the cold-sphere contrast values at 10, 20, and 40 mA were -0.33, -0.16, and 0.08.
      CONCLUSIONS: Although the linear attenuation coefficients in the 300-mm phantom
      remained the same with varying CT tube currents, the 500-mm phantom yielded
      significant differences in the range 10-40 mA. Therefore, the CT tube currents
      for attenuation correction should be adjusted over 40 mA in obese patients.

PMID- 22359225
TI  - The stress response and adolescents' adjustment: the impact of child
      maltreatment.
AB  - Experience with and management of stress has implications for adolescents'
      behavioral and socioemotional development. This study examined the relationship
      between adolescents' physiological response to an acute laboratory stressor
      (i.e., Trier Social Stress Test; TSST) and anger regulation and interpersonal
      competence in a sample of 175 low-income urban adolescents (51.8% girls).
      Findings suggested that heightened reactivity as indicated by cortisol, heart
      rate, and blood pressure was associated with increased interpersonal competence
      and anger regulation. However, these findings were context dependent such that,
      for youth high in self-reported child maltreatment, heightened reactivity was
      associated with decreased interpersonal competence and anger regulation. Results
      highlight the importance of considering how context may condition the effect of
      stress reactivity on functioning during adolescence.

PMID- 22359226
TI  - The limitations of small outcome studies.

PMID- 22359227
TI  - Epidermal growth factor receptor and K-Ras mutations and resistance of lung
      cancer to insulin-like growth factor 1 receptor tyrosine kinase inhibitors.
AB  - BACKGROUND: Most patients with nonsmall cell lung cancer (NSCLC) have responded
      poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs). The authors investigated the involvement of insulinlike growth factor 1
      receptor (IGF-1R) signaling in primary resistance to EGFR TKIs and the molecular
      determinants of resistance to IGF-1R TKIs. METHODS: Phosphorylated IGF-1R/insulin
      receptor (pIGF-1R/IR) was immunohistochemically evaluated in an NSCLC tissue
      microarray. The authors analyzed the antitumor effects of an IGF-1R TKI (PQIP or
      OSI-906), either alone or in combination with a small-molecular inhibitor
      (PD98059 or U0126) or with siRNA targeting K-Ras or mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase (MEK), in vitro and in vivo
      in NSCLC cells with variable histologic features and EGFR or K-Ras mutations.
      RESULTS: pIGF-1R/IR expression in NSCLC specimens was associated with a history
      of tobacco smoking, squamous cell carcinoma histology, mutant K-Ras, and wild
      type (WT) EGFR, all of which have been strongly associated with poor response to
      EGFR TKIs. IGF-1R TKIs exhibited significant antitumor activity in NSCLC cells
      with WT EGFR and WT K-Ras but not in those with mutations in these genes.
      Introduction of mutant K-Ras attenuated the effects of IGF-1R TKIs on NSCLC cells
      expressing WT K-Ras. Conversely, inactivation of MEK restored sensitivity to IGF
      TKIs in cells carrying mutant K-Ras. CONCLUSIONS: The mutation status of both
      EGFR and K-Ras could be a predictive marker of response to IGF-1R TKIs. Also, MEK
      antagonism can abrogate primary resistance of NSCLC cells to IGF-1R TKIs.

PMID- 22359228
TI  - Current understanding of the pathogenesis and management of chronic recurrent
      multifocal osteomyelitis.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disorder
      that primarily affects children. Its hallmark is recurring episodes of sterile
      osteomyelitis. The clinical presentation is insidious onset of bone pain with or
      without fever. Laboratory studies typically reveal nonspecific evidence of
      inflammation. Radiologic imaging and histologic appearance resemble those of
      infectious osteomyelitis. There is a strong association with inflammatory
      disorders of the skin and intestinal tract in affected individuals and their
      close relatives, suggesting a shared pathophysiology and supporting a genetic
      component to disease susceptibility. Two genetic syndromes have CRMO as a
      prominent phenotype-Majeed syndrome and deficiency of the interleukin-1 receptor
      antagonist-and suggest that interleukin-1 may be a key cytokine in disease
      pathogenesis. This review briefly summarizes the main clinical and radiologic
      aspects of the disease and then focuses on genetics and pathophysiology and
      provides an update on treatment.

PMID- 22359229
TI  - Regulation of uric acid excretion by the kidney.
AB  - It has been known for many years that the kidney plays a major role in uric acid
      homeostasis, as more than 70% of urate excretion is renal. Furthermore,
      hyperuricemia in gout is most commonly the result of relative urate
      underexcretion, as the kidney has enormous capacity for urate reabsorption. A
      clear understanding of the mechanisms of renal handling of urate has been
      hampered by the differences between humans and animal models. The power of human
      genetics and genome-wide association studies has now provided new insight into
      the molecular mechanisms of urate transport by identifying the transporters that
      have critical roles in urate transport. This review surveys the new evidence for
      a molecular model of urate transport in the renal proximal tubule and uses these
      data to refute the popular four-component model for urate transport that has long
      been in vogue. It also discusses data that help us understand the relation of
      diuretics to hyperuricemia, losartan-induced uricosuria, variations in uric acid
      levels in hyperglycemia, and the effects of dairy diets on serum urate levels. In
      the end, several of these clinical findings are explained, and the remaining gaps
      in our knowledge will become evident.

PMID- 22359230
TI  - Disentangling the emerging evidence around atypical fractures.
AB  - Atypical femur fractures are rare but a growing concern, as they are more common
      in patients who use bisphosphonates. The best radiology-based studies have had
      access to only short-term exposure data, while the studies using prescription
      databases with substantial long-term data did not have access to radiology
      reports. The interests of the patients are probably best served by reserving long
      term bisphosphonate treatment for patients who are at the highest risk of
      osteoporotic fractures and considering drug holidays after 5 years in patients at
      low risk. Recent studies have further strengthened the case for active medical or
      surgical therapy in patients with incomplete fractures, but patient numbers are
      small, and randomized controlled trials may not be forthcoming in the immediate
      future. The recommendations made to establish an international database for such
      fractures have not yet been followed, and more epidemiologic and pathophysiologic
      research is needed.

PMID- 22359231
TI  - Patterns of failure after treatment of atypical meningioma with gamma knife
      radiosurgery.
AB  - Atypical meningiomas have poor local control with emerging literature indicating
      the use of radiosurgery in treatment. The purpose of this study was to evaluate
      clinical outcomes including local control and failure pattern after Gamma Knife
      radiosurgery (GKRS) and factors that may affect these outcomes. Between 1999 and
      2008, 24 patients were treated with GKRS as either primary or salvage treatment
      for pathologically proven atypical meningiomas. Treatment failures were
      determined by serial magnetic resonance imaging. A median marginal dose of 14 Gy
      was used (range 10.5-18 Gy). Overall local control rates at 1, 2, and 5 years
      were 75, 51, and 44%, respectively. With median follow-up time of 42.5 months, 14
      of 24 patients experienced a treatment failure at time of last follow-up. Eight
      recurrences were in-field, four were marginal failures, and two were distant
      failures. Wilcoxon analysis revealed that the conformality index (CI) was a
      significant predictor of local recurrence (P = 0.04). CI did not predict for
      distant recurrences (P = 0.16). On multivariate analysis evaluating factors
      predicting progression free survival, dose >14 Gy was found to be statistically
      significant (P = 0.01). There appears to be a dose response using GKRS beyond 14
      Gy but given the suboptimal local control rates in this study, higher doses may
      still be needed to obtain better local control.

PMID- 22359232
TI  - Analysis of an incomplete binary outcome derived from frequently recorded
      longitudinal continuous data: application to daily pain evaluation.
AB  - Randomized clinical trials increasingly collect daily data, frequently using
      electronic diaries. Such data are usually summarized into an 'intermediate'
      continuous outcome (such as the mean of the daily values in a period before a
      scheduled clinic visit). These are in turn often summarized further into a binary
      outcome, for example, indicating whether the intermediate continuous outcome has
      improved by a prespecified amount from randomization. This article compares and
      contrasts statistical approaches for analyzing such binary outcomes when the
      underlying study is subject to dropout so that some of the underlying diary data
      are missing. Such analysis involves rigorous rules for the derivation of
      outcomes, a thorough data exploration for the selection of covariates, and an
      elucidation of the missingness mechanism. The investigated statistical methods
      for treatment-effect analysis are based on direct modeling and on multiple
      imputation and are applied either to the binary outcome or the intermediate
      continuous outcome or to the daily diary data. These are compared on the basis of
      criteria for inferences at prespecified times during the follow-up. We show that
      multiple-imputation methods are particularly well adapted to our context and that
      missing data imputation on the daily diary data, rather than the derived
      outcomes, makes best use of the available information. The data set, which
      motivated our investigation, comes from a placebo-controlled clinical trial to
      assess the effect on pain of a new compound.

PMID- 22359233
TI  - Flagella and bacterial pathogenicity.
AB  - As locomotive organelles, flagella allow bacteria to move toward favorable
      environments. A flagellum consists of three parts: the basal structure (rotary
      motor), the hook (universal joint), and the filament (helical propeller). For
      ages, flagella have been generally regarded as important virulence factors,
      mainly because of their motility property. However, flagella are getting
      recognized to play multiple roles with more functions besides motility and
      chemotaxis. Recent evidence has pinpointed that the bacterial flagella
      participate in many additional processes including adhesion, biofilm formation,
      virulence factor secretion, and modulation of the immune system of eukaryotic
      cells. This mini-review summarizes data from recent studies that elucidated how
      flagella, as a virulence factor, contribute to bacterial pathogenicity.

PMID- 22359234
TI  - Cloning and ontogenetic expression of the uncoupling protein 1 gene UCP1 in
      sheep.
AB  - The uncoupling protein 1 (UCP1) is an indicator of brown adipocytes and is
      involved in the control of body temperature and regulation of energy balance. It
      abundantly expresses in newborns and has important functions in adults. However,
      little information was known on UCP1 gene expression in young and adolescent
      sheep. In this study, we cloned and identified the full-length DNA and cDNA
      sequences of the ovine UCP1 gene, which were 6659 bp and 1621 bp, respectively,
      and predicted the location of the gene on chromosome 17. Forty-eight animals with
      an equal number of males and females each for both Guangling Large Tail sheep
      (GLT) and Small Tail sheep Han (STH) sheep were used to study the ontogenetic
      expression of UCP1 mRNA in eight adipose tissues by quantitative real-time
      polymerase chain reaction (PCR). The results showed that the mRNA was expressed
      in all tissues studied and at all stages from 2 to 12 months of age.
      Nevertheless, the mRNA in perirenal fat was expressed significantly higher than
      that in other tissues and lower in superficial fat than in deep deposits. The
      highest expression was observed in animals at 2 months of age and then decreased
      gradually with age. Global expression in GLT was significantly higher than that
      in STH. Interactions between tissue and breed and age also influenced the mRNA
      expression significantly. In addition, the mRNA expression was associated with
      the single nucleotide polymorphism (SNP) haplotypes detected in the cDNA of the
      gene.

PMID- 22359236
TI  - Cost effectiveness of gene expression profiling for early stage breast cancer: a
      decision-analytic model.
AB  - BACKGROUND: Gene expression profiling (GEP) is being used increasingly for risk
      stratification to identify women with lymph node-negative, estrogen receptor
      positive, early stage breast cancer who are most likely to benefit from adjuvant
      chemotherapy. The authors of this report evaluated the cost effectiveness of
      recurrence score-guided treatment using 2 commercially available GEP tests,
      Oncotype DX (Genomic Health, Redwood City, Calif) and MammaPrint (Agendia Inc.,
      Irvine, Calif), from a third-party payer's perspective. METHODS: A 10-year Markov
      model was developed to compare the costs and quality-adjusted life-years (QALYs)
      of treatment decisions guided by either Oncotype DX or MammaPrint in a
      hypothetical cohort of women with early stage, lymph node-negative, estrogen
      receptor-positive breast cancer who may experience recurrence. Outcomes included
      no recurrence, recurrence, and death. The costs considered included gene test
      costs, the costs of adjuvant chemotherapy and other chemotherapy (including
      premedication, oncology visits, and monitoring for adverse events), the cost of
      treating recurrence, costs associated with the treatment of adverse events, and
      end-of-life care costs. RESULTS: The model demonstrated that the patients who
      received the Oncotype DX test to guide treatment spent $27,882 (in US dollars)
      and gained 7.364 QALYs, whereas patients who received the MammaPrint test to
      guide treatment spent $21,598 and gained 7.461 QALYs. Sensitivity analyses
      demonstrated that the results were robust to changes in all parameters.
      CONCLUSIONS: The model suggested that MammaPrint is a more cost-effective GEP
      test compared with Oncotype DX at a threshold willingness-to-pay of $50,000 per
      QALY. Because Oncotype DX is the most frequently used GEP in clinical practice in
      the United States, the authors concluded that the current findings have
      implications for health policy, particularly health insurance reimbursement
      decisions.

PMID- 22359235
TI  - Stathmin expression and its relationship to microtubule-associated protein tau
      and outcome in breast cancer.
AB  - BACKGROUND: Microtubule-associated proteins (MAPs) endogenously regulate
      microtubule stability. Here, the prognostic value of stathmin, a destabilizing
      protein, was assessed in combination with MAP-tau, a stabilizing protein, in
      order to evaluate microtubule stabilization as a potential biomarker. METHODS:
      Stathmin and MAP-tau expression levels were measured in a breast cancer cohort (n
      = 651) using the tissue microarray format and quantitative immunofluorescence
      (AQUA) technology, then correlated with clinical and pathological characteristics
      and disease-free survival. RESULTS: Univariate Cox proportional hazard models
      indicated that high stathmin expression predicts worse overall survival (hazard
      ratio [HR] = 1.48; 95% confidence interval [CI] = 1.119-1.966; P = .0061).
      Survival analysis showed 10-year survival of 53.1% for patients with high
      stathmin expression versus 67% for low expressers (log-rank, P < .003). Cox
      multivariate analysis showed high stathmin expression was independent of age,
      menopausal status, nodal status, nuclear grade, tumor size, and estrogen
      receptor, progesterone receptor, and human epidermal growth factor receptor 2
      expression (HR = 1.19; 95% CI = 1.03-1.37; P = .01). The ratio of MAP-tau to
      stathmin expression showed a positive correlation to disease-free survival (HR =
      0.679; 95% CI = 0.517-0.891; P = .0053) with a 10-year survival of 65.4% for
      patients who had a high ratio of MAP-tau to stathmin versus 52.5% 10-year
      survival rate for those with a low ratio (log-rank, P = .0009). Cox multivariate
      analysis showed the ratio of MAP-tau to stathmin was an independent predictor of
      overall survival (HR = 0.609; 95% CI = 0.422-0.879; P = .008). CONCLUSIONS: Low
      stathmin and high MAP-tau are associated with increased microtubule stability and
      better prognosis in breast cancer.

PMID- 22359237
TI  - The influence of parental education on child mental health in Spain.
AB  - PURPOSE: To analyze the association between parental education and offspring's
      mental health in a nationally representative Spanish sample, and assess the
      contribution of other socioeconomic factors to the association. METHODS: We
      conducted a secondary analysis of data on 4- to 15-year-olds participating in the
      2006 Spanish National Health Survey. Mental health was assessed using the parent
      reported Strengths & Difficulties Questionnaire. Parents' respective educational
      levels were summarized in a single variable. Univariate and multivariate
      analyses, controlling for family-, child- and parent-related characteristics,
      were used to study the association. RESULTS: The final sample comprised 5,635
      children. A strong association between parental education and parent-reported
      child mental health was observed among 4- to 11-year-olds, with odds ratios (ORs)
      increasing as parental educational level decreased. Where both parents had a sub
      university level, maternal education showed a stronger association than did
      paternal education. Following adjustment for covariates, parental education
      continued to be the strongest risk factor for parent-reported child mental health
      problems, OR = 3.7 (95% CI 2.4-5.8) for the lowest educational level, but no
      association was found among 12- to 15-year-olds. Male sex, immigrant status,
      activity limitation, parent's poor mental health, low social support, poor family
      function, single-parent families, low family income and social class were
      associated with parent-reported child mental health problems in both age groups.
      CONCLUSIONS: Our results show that there is a strong association between parental
      education and parent-reported child mental health, and that this is indeed
      stronger than that for income and social class. Among adolescents, however, the
      effect of parental education would appear to be outweighed by other factors.

PMID- 22359239
TI  - Rapid and simultaneous detection of linear chromosome and large plasmids in
      Proteobacteria.
AB  - Bacterial genomic architectures are complex and play important roles in genome
      evolution. While most bacterial lineage genomes contain a single chromosome often
      accompanied by plasmids, more and more genomes are described as harboring a
      linear or a second chromosome. Thus, the development of bacterial genomics leads
      to the study of bacterial genome architectures. In order to avoid laborious
      techniques combining several methods, we developed an original plug-free pulsed
      field gel electrophoresis procedure, that enabled us to co-characterize
      reproducibly the presence of linear chromosomes and plasmids ranging between 30
      kb and 2000 kb in various proteobacterial lineages.

PMID- 22359238
TI  - Effect of the fungal mycotoxin patulin on the chromatin structure of fission
      yeast Schizosaccharomyces pombe.
AB  - The fungal mycotoxin patulin is produced by several molds, especially by
      Aspergillus and Penicillium. The aim of this study was to clarify whether patulin
      causes alterations in plasma membrane permeability of Schizosaccharomyces pombe
      lead to cellular shrinkage charateristic to apoptosis or increases cell size
      indicating necrosis in cells. Transmission and scanning electronmicroscopy
      revealed that lower concentrations of patulin induced cellular shrinkage and
      blebbing, higher concentration caused expansion without cellular disruption.
      Large-scale morphological changes of individual cells were followed by time lapse
      video microscopy. Patulin caused the elongation and stickiness of cells or
      rounded up their shapes. To visualize chromatin structures of S. pombe nuclei
      upon patulin treatment, protoplasts were isolated from S. pombe and subjected to
      fluorescent microscopy. Chromatin changes in the presence of 50 MUM patulin
      concentration were characterized by elongated nuclei containing sticky fibrillary
      chromatin and enlarged round shaped nuclei trapped at the fibrillary stage of
      chromatin condensation. Short (60 min) incubation of S. pombe cells in the
      presence of high (500 MUM) patulin concentration generated patches of condensed
      chromatin bodies inside the nucleus and caused nuclear expansion, with the rest
      of chromatin remaining in fibrillary form. Longer (90 min, 500 MUM) incubation
      resulted in fewer highly condensed chromatin patches and in nuclear
      fragmentation. Although, high patulin concentration increased the size of S.
      pombe size, it did not lead to necrotic explosion of cells, neither did the
      fragmented nuclei resemble apoptotic bodies that would have indicated programmed
      cell death. All these morphological changes and the high rate of cell survival
      point to rapid adaptation and mixed type of fungistatic effects.

PMID- 22359240
TI  - Impact of financial and educational interventions on maternity care: results of
      cluster randomized trials in rural China, CHIMACA.
AB  - To report on the design and basic outcomes of three interventions aimed at
      improving the use and quality of maternity care in rural China: financial
      interventions, training in clinical skills, and training in health education.
      Community-based cluster randomized trials were carried out in one central and two
      western provinces between 2007 and 2009: (1) financial interventions covered part
      of women's costs for prenatal and postnatal care, (2) training of midwives in
      clinical skills was given by local maternity care experts in two- or three-group
      training courses, (3) health education training for midwives and village doctors
      were given by local experts in health education in two- or three-group training
      courses. A survey was conducted in a stratified random sample of women who had
      been pregnant in the study period. 73% of women (n = 3,673) were interviewed
      within 1-10 months of giving birth. Outcomes were compared by the different
      intervention and control groups. Adjusted odds ratios were calculated by logistic
      regression to adjust for varying maternal characteristics. Most of the
      differences found between the groups were small and some varied between
      provinces. The financial intervention did not influence the number of visits, but
      was associated with increased caesarean sections and a decrease in many
      ultrasound tests. The clinical intervention influenced some indicators of care
      content. There was no consistent finding for the health education intervention.
      Financial and training interventions have the potential to improve maternity
      care, but better implementation is required. Unintended consequences, including
      overuse of technology, are possible.

PMID- 22359241
TI  - 'A normal delivery takes place at home': a qualitative study of the location of
      childbirth in rural Ethiopia.
AB  - To identify reasons why women who access health facilities and utilise maternal
      newborn and child health services at other times, do not necessarily deliver at
      health facilities. Forty-six semi-structured interviews were conducted with
      mothers who had recently delivered (n = 30) or were pregnant (n = 16). Thematic
      analysis of the interview data resulted in emerging trends that were critically
      addressed according to the research objective. Of the 30 delivered cases, 14 had
      given birth at a health facility, but only 3 of those had planned to do so. The
      remaining 11 had attended due to long or complicated labours. Five dominant
      themes influencing location of delivery were identified: perceptions of a normal
      delivery; motivations encouraging health facility delivery; deterrents preventing
      health facility deliveries; decision-making processes; and level of knowledge and
      health education. Understanding the socio-cultural determinants that influence
      the location of delivery has implications for service provision. Alongside timely
      health education and maximising the contact between women and healthcare
      professionals, these determinants should be actively incorporated into maternal
      newborn and child health policy and programming in ways that encourage the
      utilisation of health facilities, even for routine deliveries.

PMID- 22359242
TI  - Pregnancy 101: a call for reproductive and prenatal health education in college.
AB  - The objective of the study was to demonstrate the effectiveness of a college
      course in preconception health and prenatal development at improving reproductive
      health awareness in college students. Students enrolled in the course completed
      pretest and posttest assessments and a course evaluation. Students' self
      perception of awareness of the positive and negative factors that can affect
      pregnancy increased from 13% at the beginning of the course to 89 and 93% at the
      end of the course, respectively. Correspondingly, students' knowledge of course
      related information improved across nearly all areas assessed. The average score
      among students increased from 67 to 90% correct from pretest to posttest. Course
      evaluation results indicated that over 94% of students found the course to be
      beneficial and informative. College courses are a practical way to disseminate
      reproductive and prenatal health information. Educating college students in these
      areas has clear benefits to both individual students and society and, as such,
      merits increased attention in college curricula.

PMID- 22359243
TI  - Does health insurance continuity among low-income adults impact their children's
      insurance coverage?
AB  - Parent's insurance coverage is associated with children's insurance status, but
      little is known about whether a parent's coverage continuity affects a child's
      coverage. This study assesses the association between an adult's insurance
      continuity and the coverage status of their children. We used data from a
      subgroup of participants in the Oregon Health Care Survey, a three-wave, 30-month
      prospective cohort study (n = 559). We examined the relationship between the
      length of time an adult had health insurance coverage and whether or not all
      children in the same household were insured at the end of the study. We used a
      series of univariate and multivariate logistic regression models to identify
      significant associations and the rho correlation coefficient to assess
      collinearity. A dose response relationship was observed between continuity of
      adult coverage and the odds that all children in the household were insured.
      Among adults with continuous coverage, 91.4% reported that all children were
      insured at the end of the study period, compared to 83.7% of adults insured for
      19-27 months, 74.3% of adults insured for 10-18 months, and 70.8% of adults
      insured for fewer than 9 months. This stepwise pattern persisted in logistic
      regression models: adults with the fewest months of coverage, as compared to
      those continuously insured, reported the highest odds of having uninsured
      children (adjusted odds ratio 7.26, 95% confidence interval 2.75, 19.17).
      Parental health insurance continuity is integral to maintaining children's
      insurance coverage. Policies to promote continuous coverage for adults will
      indirectly benefit children.

PMID- 22359244
TI  - 3-O-acetyloleanolic acid induces apoptosis in human colon carcinoma HCT-116
      cells.
AB  - The cytotoxic effect of 3-O-acetyloleanolic acid, an oleanolic acid derivative
      isolated from the seeds of Vigna sinensis K., was investigated in human colon
      carcinoma HCT-116 cells. 3-O-acetyloleanolic acid dose-dependently inhibited the
      viability of HCT-116 cells. Apoptosis was characterized by detection of cell
      surface annexin V and sub-G1 apoptotic cell populations. The number of
      immunostained cells with annexin V-FITC was increased after treatment with 3-O
      acetyloleanolic acid. The sub-G1 cell population was also increased. Expression
      of TRAIL-mediated apoptosis signaling-related death receptor DR5 was increased in
      3-O-acetyloleanolic acid-treated HCT-116 cells. Activation of caspase-8 and
      caspase-3, critical mediators of extrinsic apoptosis signaling, was also
      increased by 3-O-acetyloleanolic acid. The results indicate that 3-O
      acetyloleanolic acid induces apoptosis in HCT-116 cells mediated by an extrinsic
      apoptosis signaling cascade via up-regulation of DR5.

PMID- 22359245
TI  - Use of sequential-batch fermentations to characterize the impact of mild
      hypothermic temperatures on the anaerobic stoichiometry and kinetics of
      Saccharomyces cerevisiae.
AB  - This work presents a characterization of the stoichiometry and kinetics of
      anaerobic batch growth of Saccharomyces cerevisiae at cultivation temperatures
      between 12 and 30 degrees C. To minimize the influence of the inoculum condition
      and ensure full adaptation to the cultivation temperature, the experiments were
      carried out in sequencing batch reactors. It was observed that the growth rate
      obtained in the first batch performed after each temperature shift was 10-30%
      different compared with the subsequent batches at the same temperature, which
      were much more reproducible. This indicates that the sequencing batch approach
      provides accurate and reproducible growth rate data. Data reconciliation was
      applied to the measured time patterns of substrate, biomass, carbon dioxide and
      byproducts with the constraint that the elemental conservation relations were
      satisfied, allowing to obtain consistent best estimates of all uptake and
      secretion rates. Subsequently, it was attempted to obtain an appropriate model
      description of the temperature dependency of these rates. It was found that the
      Ratkowsky model provided a better description of the temperature dependency of
      growth, uptake and secretion rates than the Arrhenius law. Most interesting was
      to find that most of the biomass-specific rates have the same temperature
      dependency, leading to a near temperature independent batch stoichiometry.

PMID- 22359246
TI  - Innate immune interferon responses to human immunodeficiency virus-1 infection.
AB  - Type I interferon (IFN) responses represent the canonical host innate immune
      response to viruses, which serves to upregulate expression of antiviral
      restriction factors and augment adaptive immune defences. There is clear evidence
      for type I IFN activity in both acute and chronic HIV-1 infection in vivo, and
      plasmacytoid dendritic cells have been identified as one important source for
      these responses, through innate immune detection of viral RNA by Toll-like
      receptor 7. In addition, new insights into the molecular mechanisms that trigger
      induction of type I IFNs suggest innate immune receptors for viral DNA may also
      mediate these responses. It is widely recognised that HIV-1 restriction factors
      share the characteristic of IFN-inducible expression, and that the virus has
      evolved to counteract these antiviral mechanisms. However, in some target cells,
      such as macrophages, IFN can still effectively restrict virus. In this context,
      HIV-1 shows the ability to evade innate immune recognition and thereby avoid
      induction of type I IFN in order to successfully establish productive infection.
      The relative importance of evasion of innate immune detection and evasion of IFN
      inducible restriction in the natural history of HIV-1 infection is not known, and
      the data suggest that type I IFN responses may play a role in both viral control
      and in the immunopathogenesis of progressive disease. Further study of the
      relationship between HIV-1 infection and type I IFN responses is required to
      unravel these issues and inform the development of novel therapeutics or vaccine
      strategies.

PMID- 22359247
TI  - Atrial fibrillation after but not before primary angioplasty for ST-segment
      elevation myocardial infarction of prognostic importance.
AB  - AIM: In patients with ST-segment elevation myocardial infarction (STEMI), it is
      uncertain whether atrial fibrillation has prognostic implications. There may be a
      difference between atrial fibrillation before and after reperfusion therapy.
      METHODS AND RESULTS: In patients with STEMI treated with primary percutaneous
      coronary intervention (PCI), ECGs were analysed before and after primary PCI. Of
      the 1623 patients with electrocardiographic data before primary PCI, 53 patients
      (3.3%) had atrial fibrillation. Patients with atrial fibrillation were older,
      were more often female, and less often had anterior MI location. Of the 1728
      patients with electrocardiographic data after primary PCI, 52 patients (3.0%) had
      atrial fibrillation. Atrial fibrillation was more common in older patients and in
      those with Killip class >1. Also patients with occlusion of the right coronary
      artery or TIMI flow 0 before primary PCI more commonly had AF after the
      procedure. Not successful reperfusion was also associated with a higher incidence
      of AF after primary PCI. Although both atrial fibrillation before and after
      primary PCI were associated with increased mortality, multivariable analyses,
      adjusting for differences in age, gender and Killip class on admission, revealed
      that atrial fibrillation after PCI (OR 3.69, 95% CI 1.87-7.29) but not before PCI
      (OR 1.86, 95% CI 0.89-3.90) was independent and statistically significantly
      associated with long-term mortality. CONCLUSION: In patients with STEMI, atrial
      fibrillation after but not before primary PCI has independent prognostic
      implications. Possibly, atrial fibrillation after the PCI is a symptom of failed
      reperfusion and a sign of heart failure.

PMID- 22359248
TI  - Long-term prognosis of patients with cardiac syndrome X: a review.
AB  - AIMS: Follow-up studies of patients with cardiac syndrome X (CSX) generally
      report good prognosis. However, some recent studies report an adverse outcome for
      women. METHODS AND RESULTS: Structured literature search and meta-analysis for
      studies regarding prognosis of cardiac syndrome X patients. We identified 85
      studies, ultimately selecting 16 for inclusion. Meta-analysis yielded a pooled
      major cardiac event percentage of 1.5% per 5 years and a pooled vascular event
      percentage of 4.8% per 5 years (n = 16 studies, n = 1694 patients). Fourteen
      studies reported upon the recurrence rate of angina pectoris: the pooled
      percentage of angina recurrence was 55% (n = 1336 patients). CONCLUSION: The
      present review of recent archival literature demonstrates an overall major
      cardiac event rate of 1.5% per 5 years. Although this is an excellent prognosis
      for CSX patients, the quality of life is impaired because of the high recurrence
      rate of angina pectoris (55%).

PMID- 22359249
TI  - Differential diagnosis of infarct-like intracranial ectopic germinomas and
      subacute lacunar infarct on susceptibility-weighted imaging.
AB  - PURPOSE: To determine the efficacy of susceptibility-weighted imaging (SWI) in
      the differential diagnosis between basal ganglia (BG) infarct-like early stage
      intracranial ectopic germinomas (IEGs) and subacute lacunar infarct (SLI).
      MATERIALS AND METHODS: Six children with early stage BG IEGs displaying an
      infarct-like episode proven by pathology and eight children with BG SLI proven by
      clinic and vascular imaging were investigated retrospectively. On SWI, the
      contrast-to-noise ratio (CNR) in abnormal signal intensity regions was calculated
      and compared between the two groups. RESULTS: For both IEGs and SLI the BG
      lesions were invisible or showed slight hyperintensity/hypointensity on T1
      weighted images and diffusion-weighted images, patchy slight hyperintensity on T2
      weighted images without mass effect, and variable enhancement on postcontrast
      magnetic resonance imaging (MRI). On SWI, obvious hypointensity in BG lesions and
      pineal gland (PG) was found in IEG patients but unremarkable in SLI patients. The
      CNRs of BG lesions and PG were significantly higher in IEG patients compared with
      those in SLI patients (P < 0.01). CONCLUSION: SWI is useful in differentiating
      IEGs from SLI when clinical symptoms and conventional MRI manifestations overlap
      in these two conditions. PG may be involved with tumor, although it is normal on
      conventional MRI in patients with IEGs.

PMID- 22359250
TI  - Psychometric validation of the Female Sexual Function Index (FSFI) in cancer
      survivors.
AB  - BACKGROUND: The Female Sexual Function Index (FSFI) is the most commonly used
      self-report instrument to measure sexual functioning among women cancer
      survivors. Despite this, the validity and reliability of the FSFI for use in
      cancer populations has not been established. METHODS: Data were combined from 3
      separate institutional review board-approved studies of the psychosexual
      adjustment of women cancer survivors conducted at Memorial Sloan-Kettering Cancer
      Center. Psychometric analysis was applied to the FSFI responses from 181 women
      comprising 4 cohorts, including survivors of: gynecologic cancer (all types; 2
      cohorts), malignancies requiring bone-marrow/stem cell transplantation, and early
      stage cervical cancer. RESULTS: A factor analysis supported the subscale
      structure of the FSFI, yielding results nearly identical to those from the
      original FSFI validation study. Internal consistency reliability was 0.94 for the
      FSFI total score and ranged from 0.85 to 0.94 for the domain scores. Corrected
      item-total correlations ranged from 0.44 to 0.79 for the total score and from
      0.62 to 0.88 for the domain scores. FSFI scores were correlated negatively with
      measures of depression, distress, and menopausal symptoms and were correlated
      positively with quality of life. FSFI scores exhibited a preliminary ability to
      discriminate between women based on whether or not they received chemotherapy
      and/or radiation. CONCLUSIONS: The FSFI demonstrated strong psychometric
      properties in this study, supporting its continued use for monitoring sexual
      function and cancer-related dysfunction among sexually active women who are
      cancer survivors.

PMID- 22359253
TI  - An action video clip database rated for familiarity in China and Germany.
AB  - Stimulus material for studying object-directed actions is needed in different
      research contexts, such as action observation, action memory, and imitation.
      Action items have been generated many times in individual laboratories across the
      world, but they are used in very few experiments. For future studies in the
      field, it would be worthwhile to have a larger set of action stimulus material
      available to a broader research community. Some smaller action databases have
      already been published, but those often focus on psycholinguistic parameters and
      static action stimuli. With this article, we introduce an action database with
      dynamic action stimuli. The database contains action descriptions of 1,754 object
      directed actions that have been rated for familiarity in Germany and in China.
      For 784 of these actions, action video clips are available. With the use of our
      database, it is possible to identify actions that differ in familiarity between
      Western and Eastern cultures. This variable may be of interest to some
      researchers in the field, since it has been shown that familiarity influences
      action information processing. Action descriptions are listed and categorized in
      tables that can be downloaded, along with the corresponding video clips, as
      supplemental material.

PMID- 22359254
TI  - Increased risk of histologically defined cancer subtypes in human
      immunodeficiency virus-infected individuals: clues for possible immunosuppression
      related or infectious etiology.
AB  - BACKGROUND: Malignancies that occur in excess among human immunodeficiency virus
      (HIV)-infected individuals may be caused by immunosuppression or infections.
      Because histologically defined cancer subtypes have not been systematically
      evaluated, their risk was assessed among people with acquired immunodeficiency
      syndrome (AIDS). METHODS: Analyses included 569,268 people with AIDS from the
      HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and
      cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were
      estimated to compare cancer risk in people with AIDS to the general population
      overall, and stratified by age, calendar period (a proxy of changing HIV
      therapies), and time since onset of AIDS (a proxy of immunosuppression). RESULTS:
      Sixteen individual cancer histologies or histology groupings manifested
      significantly elevated SIRs. Risks were most elevated for adult T cell
      leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid
      cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise
      specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma,
      bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma
      not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ
      cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic
      leukemia, and myeloid leukemias. For several of these cancer subtypes,
      significant declines in SIRs were observed across calendar periods (consistent
      with decreasing risk with improved HIV therapies) or increase in SIRs with time
      since onset of AIDS (ie, prolonged immunosuppression). CONCLUSIONS: The elevated
      risk of certain cancer subtypes in people with AIDS may point to an etiologic
      role of immunosuppression or infection. Future studies are needed to further
      investigate these associations and evaluate candidate infectious agents.

PMID- 22359256
TI  - Gaining momentum in the long, uphill battle to "get to zero".
AB  - I am truly privileged to be addressing you for the first time in the Journal of
      Healthcare Risk Management. I'm looking forward to getting to know you and
      working with you. I want to learn more about all the great ways that each of you
      has been making a difference in keeping our patients safe and building trust in
      our healthcare systems. As you know, the ASHRM Board is completely committed to
      finding solutions through the empowerment of our members. We believe in you. In
      that spirit, we are coming up with new ways to fund research and make critical
      connections that will fuel ideas.

PMID- 22359257
TI  - The changing face of healthcare.
AB  - There seems to be a theme in many publications, books, and media channels lately,
      and that theme is change. There are changes in global markets, economic factors,
      and healthcare reform, to name a few, and change.gov is a government Web site.
      Much discussion has taken place in the past year or so about embracing change,
      leading change, and overcoming change through resilience. As I look forward into
      2012, I am indeed thinking about change.

PMID- 22359255
TI  - Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell
      function within 2 weeks after gastric bypass in non-diabetic subjects.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in
      secretion of gastrointestinal hormones and glucose metabolism. We present a
      detailed analysis of the early hormone changes after RYGB in response to three
      different oral test meals designed to provide this information without causing
      side effects (such as dumping). METHODS: We examined eight obese non-diabetic
      patients before and within 2 weeks after RYGB. On separate days, oral glucose
      tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid
      mixed meal test (200 mL 300 kcal) were performed. We measured fasting and
      postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon
      like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP),
      glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK),
      total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP),
      amylin, leptin, free fatty acids (FFA), and registered postprandial dumping.
      Insulin sensitivity was measured by homeostasis model assessment of insulin
      resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were
      significantly decreased and FFA was elevated postoperatively. Insulin sensitivity
      increased after surgery. The postprandial response increased for C-peptide, GLP
      1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased
      for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP,
      amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ
      before and after the operation or between the tests. CONCLUSIONS: Within 2 weeks
      after RYGB, we found an increase in insulin secretion and insulin sensitivity.
      Responses of appetite-regulating intestinal hormones changed dramatically, all in
      the direction of reducing hunger.

PMID- 22359258
TI  - Successful risk assessment may not always lead to successful risk control: A
      systematic literature review of risk control after root cause analysis.
AB  - Root cause analysis is perhaps the most widely used tool in healthcare risk
      management, but does it actually lead to successful risk control? Are there
      categories of risk control that are more likely to be effective? And do
      healthcare risk managers have the tools they need to support the risk control
      process? This systematic review examines how the healthcare sector translates
      risk analysis to risk control action plans and examines how to do better. It
      suggests that the hierarchy of risk controls should inform risk control action
      planning and that new tools should be developed to improve the risk control
      process.

PMID- 22359259
TI  - Nurse staffing and skill mix patterns: Are there differences in outcomes?
AB  - The purpose of this study was to examine the impact on patient outcomes of nurse
      staffing and registered nurse (RN) skill mix patterns used by medical-surgical
      units in California hospitals after enactment of nurse-to-patient staffing ratio
      laws, and determine if there are differences in patient outcomes for conditions
      that are considered sensitive to nursing care. Results from this study
      demonstrated an association between total nursing hours per patient day (NHPPD)
      and two outcomes: urinary tract infections (UTI) and length of stay (LOS). A
      stronger association was observed between the RN proportions of the total nursing
      hours of care and the same outcomes. The higher the total NHPPD and RN
      proportion, the lower the LOS and the lower the odds of hospitalized patients'
      developing UTI.

PMID- 22359260
TI  - Perioperative dental injury at a tertiary care health system: An eight-year audit
      of 816,690 anesthetics.
AB  - Among all complications of airway management, dental injury is the most common
      cause of patient complaints with medicolegal consequences. Over an 8-year period,
      data on dental injury were collected within a large university hospital system
      that included community, tertiary, and quaternary care centers. Patient
      characteristics were compared among all patients receiving anesthesia care using
      billing data collected from the same period. Of the 816,690 patients who received
      anesthesia care, there were 360 dental injuries, giving an overall incidence of
      1:2,269 (0.044%). Patients receiving general anesthesia were at an increased risk
      for dental injuries, with an incidence of 1:1,754 (0.057%) compared with patients
      receiving monitored anesthesia care in whom the incidence was 1:12,500 (0.008%).
      Patients in the age group 18 to 65 years had a higher incidence of dental
      injuries of 1:1,818 (0.055%) compared with pediatric patients, who had an
      incidence of 1:7,692 (0.013%). Emergency procedures were not associated with an
      increased risk of dental injury in the 816,690 cases. However, of the 360
      patients who sustained a dental injury, emergency procedures were associated with
      a higher incidence of injuring multiple teeth.

PMID- 22359261
TI  - Using prospective hazard analysis to assess an active shooter emergency
      operations plan.
AB  - Most risk management activity in the healthcare sector is retrospective, based on
      learning from experience. This is feasible where the risks are routine, but
      emergency operations plans (EOP) guide the response to events that are both high
      risk and rare. Under these circumstances, it is important to get the response
      right the first time, but learning from experience is usually not an option. This
      case study presents the rationale for taking a proactive approach to improving
      healthcare organizations' EOP. It demonstrates how the Prospective Hazard
      Analysis (PHA) Toolkit can drive organizational learning and argues that this
      toolkit may lead to more efficient improvement than drills and exercises.

PMID- 22359262
TI  - Medical malpractice. Davis v. Wooster Orthopedics & Sports Medicine, Inc.

PMID- 22359264
TI  - Production of laccase from Trametes trogii TEM H2: a newly isolated white-rot
      fungus by air sampling.
AB  - This work represents the first report of isolation of potential laccase producers
      by air sampling using media supplemented with 2,2-azinobis (3
      ethylbenzothiazoline-6-sulfonate) and guaiacol for laccase production and
      secretion indicators. Nine fungal isolates showed positive reactions with 2,2
      azinobis (3-ethylbenzothiazoline-6-sulfonate) and guaiacol. The isolate named TEM
      H2 exhibited the largest and intensive oxidation zones with 2,2-azinobis (3
      ethylbenzothiazoline-6-sulfonate) (85 mm) and guaiacol (66 mm) and therefore it
      was selected for detailed investigations. The strain was identified as Trametes
      trogii TEM H2 due to the morphological characteristics and the comparison of
      internal transcribed spacer ribosomal DNA gene sequences. The laccase production
      was screened in different liquid cultures. The best laccase production medium was
      determined as soluble starch yeast extract medium in which laccase production was
      reached to a maximum level (989.6 U l(-1) ) on the 8(th) day of cultivation.
      Effects of different initial pH values on laccase production were tested. Optimum
      pH value for laccase production in soluble starch yeast extract medium was
      determined as pH 3.0 with 15425.0 U l(-1) laccase production at 12(th) day of
      cultivation. In addition, effects of eight inducers (veratryl alcohol, ferulic
      acid, 1-Hydroxybenzotriazole, syringic acid, 2,2-azinobis (3-ethylbenzothiazoline
      6-sulfonate), 1 mmol l(-1) CuSO(4) , 3% ethanol, guaiacol) were examined. Only
      cultures with 2,5-xylidine exhibited 1.9 fold increase in laccase activity
      reaching to 28890.0 U l(-1).

PMID- 22359263
TI  - NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with
      myxoid/round cell liposarcoma.
AB  - BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common
      liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of
      all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients
      with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen
      (also known as cancer germ cell antigen) that has been successfully targeted in
      vaccine trials and in adoptive T-cell therapy trials for the treatment of several
      solid tumors. METHODS: The authors investigated the feasibility of targeting NY
      ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression
      in tumors using immunohistochemistry and quantitative reverse transcriptase
      polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO
      1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A
      search of the University of Washington Sarcoma Tissue Bank identified paraffin
      embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was
      observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was
      homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such
      patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By
      using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid
      liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS:
      The current results establish NY-ESO-1 as an important target antigen for the
      treatment of patients with MRCL.

PMID- 22359265
TI  - Efficacy of two insecticides for protecting loblolly pines (Pinus taeda L.) from
      subcortical beetles (Coleoptera: Curculionidae and Cerambycidae).
AB  - BACKGROUND: Tests were conducted on two insecticides (carbaryl and bifenthrin)
      for excluding subcortical beetles (Coleoptera: Curculionidae and Cerambycidae)
      from loblolly pine trees (Pinus taeda L.). Two trap designs (single- and double
      pane windows) and two trapping heights (1.5 and 4 m) were also evaluated for
      maximizing beetle catches. RESULTS: In July 2009, 15 loblolly pine trees were
      double girdled and were either left unsprayed or sprayed with carbaryl or
      bifenthrin. A total of 28 473 bark beetles were caught in window traps, including
      Ips avulsus Eichoff, I. grandicollis (Eichhoff), I. calligraphus (Germar) and
      Dendroctonus terebrans (Olivier). Both insecticides significantly reduced
      colonization of the trees by bark and woodboring beetles by 300-400%, with no
      differences in efficacy observed between the two insecticides. About 59% more I.
      avulsus were caught in double- than in single-pane window traps, with no
      differences for any other species. Traps at 4 m caught more I. avulsus and I.
      grandicollis (290 and 153% respectively), while traps at 1.5 m caught more D.
      terebrans (215%). CONCLUSIONS: Either bifenthrin or carbaryl can be used to
      exclude subcortical beetles from loblolly pine trees. Trapping data reflect known
      vertical partitioning on the bole by these insects. Double-pane traps were
      slightly more effective than single-pane traps in catching subcortical beetles.

PMID- 22359267
TI  - Model misspecification and robustness in causal inference: comparing matching
      with doubly robust estimation.
AB  - In this paper, we compare the robustness properties of a matching estimator with
      a doubly robust estimator. We describe the robustness properties of matching and
      subclassification estimators by showing how misspecification of the propensity
      score model can result in the consistent estimation of an average causal effect.
      The propensity scores are covariate scores, which are a class of functions that
      removes bias due to all observed covariates. When matching on a parametric model
      (e.g., a propensity or a prognostic score), the matching estimator is robust to
      model misspecifications if the misspecified model belongs to the class of
      covariate scores. The implication is that there are multiple possibilities for
      the matching estimator in contrast to the doubly robust estimator in which the
      researcher has two chances to make reliable inference. In simulations, we compare
      the finite sample properties of the matching estimator with a simple inverse
      probability weighting estimator and a doubly robust estimator. For the
      misspecifications in our study, the mean square error of the matching estimator
      is smaller than the mean square error of both the simple inverse probability
      weighting estimator and the doubly robust estimators.

PMID- 22359266
TI  - 2,5-Piperazinedione inhibits quorum sensing-dependent factor production in
      Pseudomonas aeruginosa PAO1.
AB  - The effects of 2,5-piperazinedione in reducing the production of quorum sensing
      (QS)-dependent factors in Pseudomonas aeruginosa PAO1 were assessed both in vitro
      and in vivo. 2,5-Piperazinedione exhibited a 69% reduction in the azocasein
      degrading proteolytic activity and a 48% reduction in the elastolytic activity of
      PAO1. Further, it showed 85% and 96% reduction in the production of pyocyanin and
      extracellular polymeric substances (EPS) of PAO1, respectively. In the swimming
      inhibition assay, 2,5-piperazinedione-treated PAO1 cells exhibited poor swimming
      motility in swim agar medium. In the in vivo analysis, an enhanced survival of
      PAO1-preinfected Caenorhabditis elegans was observed after treatment with 2,5
      piperazinedione. Regarding the mode of action, in the molecular docking analysis,
      2,5-piperazinedione interacts with the amino acid residue of the LasR receptor
      protein required for binding the natural ligand N -3-oxododecanoyl-l-homoserine
      lactone (3-oxo-C12-HSL). This demonstrates the probability of 2,5-piperazinedione
      to interfere with the binding process of 3-oxo-C12-HSL to its receptor protein.
      Thus, the findings of the present study reveal the potential of 2,5
      piperazinedione in reducing the QS-dependent phenotypic features of PAO1.

PMID- 22359268
TI  - Catalytic generation of arynes and trapping by nucleophilic addition and
      iodination.
AB  - A fair exchange: in the title reaction, alkynyllithium serves as an initiator for
      benzyne generation through an iodine-lithium exchange. When performed in the
      presence of stoichiometric amounts of a nucleophile, the generated benzyne
      undergoes attack by lithio nucleophiles to generate aryllithium, which is then
      iodinated by iodoalkyne to give the iodoarenes 1.

PMID- 22359269
TI  - Tricin inhibits proliferation of human hepatic stellate cells in vitro by
      blocking tyrosine phosphorylation of PDGF receptor and its signaling pathways.
AB  - 4',5,7-Trihydroxy-3',5'-dimethoxyflavone (Tricin), a naturally occurring flavone,
      has anti-inflammatory potential and exhibits diverse biological activities
      including antigrowth activity in several human cancer cell lines and cancer
      chemopreventive effects in the gastrointestinal tract of mice. The present study
      aimed to investigate the biological actions of tricin on hepatic stellate cells
      (HSCs) in vitro, exploring its potential as a treatment of liver fibrosis, since
      HSC proliferation is closely related to the progression of hepatic fibrogenesis
      in chronic liver diseases leading to irreversible liver cirrhosis and
      hepatocellular carcinoma. Tricin inhibited platelet-derived growth factor (PDGF)
      BB-induced cell proliferation by blocking cell cycle progression and cell
      migration in the human HSC line LI90 and culture-activated HSCs. It also reduced
      the phosphorylation of PDGF receptor beta and the downstream signaling molecules
      ERK1/2 and Akt, which might be due to its tyrosine kinase inhibitor properties
      rather than inhibition of the direct binding between PDGF-BB and its receptor.
      Our findings suggest that tricin might be beneficial in HSC-targeting therapeutic
      or chemopreventive applications for hepatic fibrosis.

PMID- 22359270
TI  - Optimization of indigo production by a newly isolated Pseudomonas sp. QM.
AB  - Optimization of indigo production process from indole using a newly isolated
      phenol-degrading bacterial strain was performed by Plackett-Burman design and
      response surface methodology. The strain designated as QM was identified as
      Pseudomonas sp. according to 16S rDNA analysis. Spectrum analysis of indole
      biotransformation products revealed the presence of indigo and a by-product
      indirubin. To improve indigo yield, Plackett-Burman design was used to select
      significant factors from 8 viriables. Then response surface methodology based on
      a 2(3) central composite design was used to further optimize the transformation
      process. Under the optimal conditons, strain QM can produce 27.20 mg/l indigo
      after 24 h cultivation at 30  degrees C, which was 151.3% higher than that from
      the initial conversion condition. The results indicated that Pseudomonas sp. QM
      should be a potential candidate for indigo industial production.

PMID- 22359271
TI  - Orthopaedic case of the month: Ossified calf mass in a 32-year-old woman.

PMID- 22359272
TI  - Simultaneous anterior and posterior synovectomies for treating diffuse pigmented
      villonodular synovitis.
AB  - BACKGROUND: The current treatment methods for diffuse intraarticular or
      extraarticular type pigmented villonodular synovitis (PVNS) include arthroscopic
      synovectomy or staged anterior and posterior open synovectomies. However, it is
      unclear whether simultaneous anterior and posterior synovectomies achieve local
      control and recovery of function. QUESTIONS/PURPOSES: We therefore determined the
      recurrence rate and function in patients with diffuse PVNS treated with anterior
      and posterior synovectomies and adjuvant radiotherapy. METHODS: We
      retrospectively reviewed all 19 patients with diffuse PVNS involving the knee
      treated with anterior and posterior synovectomies and adjuvant radiotherapy
      between January 2001 and November 2007. From the records, we determined local
      recurrence and Tegner-Lysholm scores. The minimum followup was 42 months (median,
      98 months; range, 42-143 months). RESULTS: Postoperative MRI revealed residual
      tumor in five of the 19 patients, although three had no disease progression
      during followup and had knee scores of 86 to 90. Two patients had recurrences at
      6 and 9 months with knee scores of 88 at 42 months and 90 at 68 months. The mean
      Tegner-Lysholm knee score improved from 59 to 93 points. Mean maximum extension
      and flexion angles improved from 11 degrees  to 2 degrees  and from 76 degrees 
      to 127 degrees , respectively. CONCLUSIONS: Compared with the literature,
      simultaneous anterior and posterior synovectomies associated with postoperative
      radiotherapy provided rates of residual or recurrent tumor and knee function
      recovery comparable to that with staged synovectomies reported in the literature.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 22359273
TI  - Arterial pharmacokinetics of red wine polyphenols: implications for novel
      endovascular therapies targeting restenosis.
AB  - Drug-eluting stents (DESs) are endovascular devices that provide controlled
      release of compounds to interfere with restenosis, an adverse outcome of
      angioplasty characterized by thickening of the arterial wall. Accumulating
      evidence suggests that arterial pharmacokinetics determine the biological effect
      and potential toxicity of stent-based therapeutics. The aim of this study was to
      examine how drug polarity, drug load, and protein binding influence release from
      a polymer film and distribution within arterial tissue. The transport and safety
      profile of resveratrol (RESV) and quercetin (QUER), two red wine polyphenols
      known to interfere with events in the pathogenesis of restenosis, were compared
      with paclitaxel (Taxol), a lipophilic drug used in DES. In bovine arteries, RESV
      showed considerable protein binding and arterial kinetics that were found to
      mimick Taxol. In contrast, the less lipophilic QUER showed limited tissue
      distribution. Measured diffusivity of RESV and QUER was coupled with a novel
      computational method for assessment of biphasic drug release kinetics and
      arterial drug retention profiles. Modeling revealed that drugs associated with
      high- and low-protein-binding affinity result in markedly distinct arterial drug
      profiles. These data underscore the importance of arterial partitioning and
      propagation of drug within arterial tissue in the rational design of DES
      coatings.

PMID- 22359274
TI  - Confocal Raman microspectroscopic study of folate receptor-targeted delivery of 6
      mercaptopurine-embedded gold nanoparticles in a single cell.
AB  - We investigate the cellular uptake behaviors and efficacy of folate-coated gold
      nanoparticles (AuNPs) for the targeted drug delivery system in human cancer
      cells. Folate-conjugated AuNPs embedded with a purine analogue cancer drug of 6
      mercaptopurine (6MP) were assembled via a 1-ethyl-3-[3-dimethylaminopropyl]
      carbodiimide hydrochloride (EDC) coupling reaction between the amino group of 4
      aminobenzenethiol (ABT) and the carboxyl group of folic acid. The assembly of
      folate and 6MP on AuNPs has been examined by absorption spectroscopy,
      transmission electron microscopy (TEM), and confocal Raman spectroscopy. The
      internalization of the conjugated AuNPs inside the folate receptor-positive HeLa
      and KB cells was checked by TEM and dark-field microscopy (DFM) combined with
      label-free confocal spectroscopy over the depth variable z at a micrometer
      resolution. DFM live cell imaging of folate-conjugated AuNPs in HeLa cells
      indicated that the targeted AuNPs appeared to attach on the cell surfaces and
      enter into the cell with an hour. The cell viability was also compared to
      estimate the efficacy of folate-conjugated AuNP delivery systems. Folate receptor
      targeted AuNP systems appeared to decrease cancer cell viability both in vitro
      and in vivo more than did the use of the 6MP-coated AuNPs drug without any
      targeting systems.

PMID- 22359276
TI  - Interleaved practice enhances skill learning and the functional connectivity of
      fronto-parietal networks.
AB  - Practice of tasks in an interleaved order generally induces superior learning
      compared with practicing in a repetitive order, a phenomenon known as the
      contextual-interference (CI) effect. Increased neural activity during interleaved
      over repetitive practice has been associated with the beneficial effects of CI.
      Here, we used psychophysiological interaction (PPI) analysis to investigate
      whether the neural connectivity of the dorsal premotor (PM) and the dorsolateral
      prefrontal (DLPFC) cortices changes when motor sequences are acquired through
      interleaved practice. Sixteen adults practiced a serial reaction time task where
      a set of three 4-element sequences were arranged in a repetitive or in an
      interleaved order on 2 successive days. On Day 5, participants were tested with
      practiced sequences to evaluate retention. A within-subjects design was used so
      that participants practiced sequences in the other condition (repetitive or
      interleaved) 2-4 weeks later. Functional magnetic resonance images were acquired
      during practice and retention. On Day 2 of practice, there was greater inter
      regional functional connectivity in the interleaved compared with the repetitive
      condition for both PM-seeded and DLPFC-seeded connectivity. The increased
      functional connectivity between both seeded regions and sensorimotor cortical
      areas correlated with the benefit of interleaved practice during later retention.
      During retention, a significant PPI effect was found in DLPFC-seeded
      connectivity, with increased DLPFC-supplementary motor area connectivity
      correlated with the benefits of interleaved practice. These data suggest that
      interleaved practice benefits learning by enhancing coordination of sensorimotor
      cortical regions, and superior performance of sequences learned under CI is
      characterized by increased functional connectivity in frontal cortex.

PMID- 22359277
TI  - Detection and differentiation of inflammatory versus fibromatous Crohn's disease
      strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and
      transabdominal ultrasound versus endoscopic/histologic evaluation.
AB  - BACKGROUND: Differentiation between inflammatory and fibromatous strictures in
      Crohn's disease (CD) is difficult but crucial for therapeutic decisions. The aim
      of this study was to assess the best noninvasive imaging method for the detection
      and differentiation of inflammatory and fibromatous stenoses in CD in comparison
      to endoscopic and histologic evaluation. METHODS: Patients with suspected CD
      strictures were included. According to a formalized endoscopic and histologic
      protocol, strictures were classified as inflammatory, mixed, and fibrostenotic.
      Strictures were further analyzed using fluorine 18-labeled fluoro-2-deoxy-D
      glucose ((18) FDG) / positron emission tomography (PET) low-dose computed
      tomography (CT), magnetic resonance (MR) enteroclysis and transabdominal
      ultrasound using standardized scoring systems. RESULTS: Thirty patients with 37
      strictures were evaluated (inflamed n = 22; mixed n = 12, fibromatous n = 3).
      (18) FDG-PET/CT detected 81%, MR-enteroclysis 81%, and ultrasound 68% of the
      strictures. Correct differentiation rates of strictures were 57% for MRE, 53% for
      (18) FDG-PET/CT, and 40% for ultrasound. Differences of detection rates and
      differentiation rates were not statistically significant. When combining
      transabdominal ultrasound with (18) FDG-PET/CT or MR-enteroclysis all strictures
      that required invasive treatment were detected. CONCLUSIONS: Detection rates of
      the strictures were not significantly different between (18) FDG-PET/CT, MR
      enteroclysis, and ultrasound. Despite good stricture detection rates relating to
      our gold standard, (18) FDG-PET/CT nor MR-enteroclysis nor ultrasound can
      accurately differentiate inflamed from fibrotic strictures. A combination of MR
      enteroclysis and ultrasound as well as a combination of (18) FDG-PET/CT and
      ultrasound resulted in a 100% detection rate of strictures requiring surgery or
      endoscopic dilation therapy, suggesting the combination of these methods as an
      alternative to endoscopy at least in the group of patients not able to perform an
      adequate bowel preparation.

PMID- 22359275
TI  - Motor learning relies on integrated sensory inputs in ADHD, but over-selectively
      on proprioception in autism spectrum conditions.
AB  - The brain builds an association between action and sensory feedback to predict
      the sensory consequence of self-generated motor commands. This internal model of
      action is central to our ability to adapt movements and may also play a role in
      our ability to learn from observing others. Recently, we reported that the
      spatial generalization patterns that accompany adaptation of reaching movements
      were distinct in children with autism spectrum disorder (ASD) as compared with
      typically developing (TD) children. To test whether the generalization patterns
      are specific to ASD, here, we compared the patterns of adaptation with those in
      children with attention deficit hyperactivity disorder (ADHD). Consistent with
      our previous observations, we found that in ASD, the motor memory showed greater
      than normal generalization in proprioceptive coordinates compared with both TD
      children and children with ADHD; children with ASD also showed slower rates of
      adaptation compared with both control groups. Children with ADHD did not show
      this excessive generalization to the proprioceptive target, but they did show
      excessive variability in the speed of movements with an increase in the
      exponential distribution of responses (tau) as compared with both TD children and
      children with ASD. The results suggest that slower rate of adaptation and
      anomalous bias towards proprioceptive feedback during motor learning are
      characteristics of autism, whereas increased variability in execution is a
      characteristic of ADHD.

PMID- 22359278
TI  - Using food to reduce H. pylori-associated inflammation.
AB  - Inflammation is widely recognized as a risk factor for gastric H. pylori
      associated disease and disruption of this process provides a potential target for
      intervention. Using an in vitro system, broccoli sprouts, manuka honey and omega
      3 oil, singly and in combination, were screened for their ability to limit H.
      pylori-associated inflammation. Each food significantly attenuated the release of
      IL-8 by H. pylori-infected cells, although the magnitude of this effect was
      variable. Only broccoli sprouts (0.125 mg/mL, w/v) were able to inhibit IL-8
      release in response to TNFalpha, suggesting it acted by a different mechanism to
      the other two foods. The combination of manuka honey (1.25%, v/v) with omega-3
      oil (0.006%, v/v) failed further to reduce IL-8 levels below those observed with
      honey alone, but the same concentrations of omega-3 oil and manuka honey
      independently enhanced the antiinflammatory effect of the isothiocyanate-rich
      broccoli sprouts. The results suggest that in the future certain foods may find
      increased clinical use as a non-antimicrobial approach for reducing the
      inflammation that is a major risk factor for H. pylori-associated disease,
      notably gastric cancer.

PMID- 22359279
TI  - Low b-value diffusion-weighted imaging: emerging applications in the body.
AB  - Thanks to recent advances in magnetic resonance imaging technology, it has become
      possible to perform intravoxel incoherent motion (IVIM) diffusion-weighted
      imaging (DWI) in any part of the body. Extracranial applications of DWI are
      currently under active investigation, especially for oncological imaging.
      However, the use of non-quantitative low b-value (10-100 s/mm(2)) DWI in the body
      is still a relatively unexplored field, and its potential is not fully
      recognized. Non-quantitative low b-value DWI may especially be useful for the
      evaluation of structures that have an inherently low signal at high b-value DWI,
      including (but not limited to) the liver, heart, and small bowel. This article
      will review and discuss the basic principles and potential applications of
      nonquantitative low b-value DWI in the body.

PMID- 22359281
TI  - MR enterography: relationship between intestinal fold pattern and the clinical
      presentation of adult celiac disease.
AB  - PURPOSE: To correlate the clinical presentation of adult celiac disease with
      various intestinal fold patterns using MR-enterography. MATERIALS AND METHODS:
      Fifty-four consecutive adult celiac patients (34 female, 20 male, 18 to 62 years)
      were studied by MR-enterography. Two radiologists blinded to the patients'
      clinical history evaluated in consensus MR studies, classifying the intestinal
      fold pattern into four categories: (a) no fold abnormalities, (b) isolated loss
      of folds in the duodenum, (c) jejunization of ileum, and (d) jejuno-ileal fold
      pattern reversal. Patients presented with the varying clinical forms of Celiac
      disease, classified as: (i) typical disease, (ii) atypical disease, and (iii)
      silent form. RESULTS: Twenty-three patients showed no intestinal fold
      abnormalities; 11 patients had isolated loss of duodenal folds; 9 patients showed
      jejunization of ileum and 11 had jejuno-ileal fold pattern reversal. 18/23 (78%)
      patients with MRI normal fold pattern had the silent clinical form of Celiac
      disease (Sensitivity 78%; specificity 100%; PPV = 1, NPV = 0.78); 9/11 (82%)
      patients with the isolated loss of duodenal folds had the atypical clinical form
      (sensitivity 82%; and specificity 100%; PPV = 1; NPV = 0.82). All 20 patients
      with the jejunization of ileum and jejuno-ileal fold pattern reversal had typical
      celiac disease (sensitivity and specificity of 100%; PPV and NPV = 1).
      CONCLUSION: MR-enterography findings in patients with celiac disease,
      demonstrates good correlation between MR findings and clinical severity.

PMID- 22359280
TI  - Identification of the HSPB4/TLR2/NF-kappaB axis in macrophage as a therapeutic
      target for sterile inflammation of the cornea.
AB  - Sterile inflammation underlies many diseases of the cornea including serious
      chemical burns and the common dry eye syndrome. In search for therapeutic targets
      for corneal inflammation, we defined the kinetics of neutrophil infiltration in a
      model of sterile injury to the cornea and identified molecular and cellular
      mechanisms triggering inflammatory responses. Neutrophil infiltration occurred in
      two phases: a small initial phase (Phase I) that began within 15 min after
      injury, and a larger second phase (Phase II) that peaked at 24-48 h. Temporal
      analysis suggested that the neuropeptide secretoneurin initiated Phase I without
      involvement of resident macrophages. Phase II was initiated by the small heat
      shock protein HSPB4 that was released from injured keratocytes and that activated
      resident macrophages via the TLR2/NF-kappaB pathway. The Phase II inflammation
      was responsible for vision-threatening opacity and was markedly suppressed by
      different means of inhibition of the HSPB4/TLR2/NF-kappaB axis: in mice lacking
      HSPB4 or TLR2, by antibodies to HSPB4 or by TNF-alpha stimulated gene/protein 6
      that CD44-dependently inhibits the TLR2/NF-kappaB pathway. Therefore, our data
      identified the HSPB4/TLR2/NF-kappaB axis in macrophages as an effective target
      for therapy of corneal inflammation.

PMID- 22359283
TI  - The use of high-solids loadings in biomass pretreatment--a review.
AB  - The use of high-solids loadings (>= 15% solids, w/w) in the unit operations of
      lignocellulose conversion processes potentially offers many advantages over lower
      solids loadings, including increased sugar and ethanol concentrations and
      decreased production and capital costs. Since the term lignocellulosic materials
      refers to a wide range of feedstocks (agricultural and forestry residues,
      distillery by-products, and dedicated energy crops like grasses), the term
      "solids loading" here is defined by the amount of dry material that enters the
      process divided by the total mass of material and water added to the material.
      The goal of this study is to provide a consolidated review of studies using a
      high-solids pretreatment step in the conversion process. Included in this review
      is a brief discussion of the limitations, such as the lack of available water to
      promote mass transfer, increased substrate viscosity, and increased concentration
      of inhibitors produced affecting pretreatment, as well as descriptions and
      findings of pretreatment studies performed at high solids, the latest reactor
      designs developed for pretreatment at bench- and pilot-scales to address some of
      the limitations, and high-solids pretreatment operations that have been scaled-up
      and incorporated into demonstration facilities.

PMID- 22359282
TI  - Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization,
      and neuronal morphology.
AB  - In a neuronal overexpression screen focused on kinases and phosphatases, one
      "hit" was the dual specificity tyrosine phosphorylation-regulated kinase (Dyrk4),
      which increased the number of dendritic branches in hippocampal neurons.
      Overexpression of various Dyrk family members in primary neurons significantly
      changed neuronal morphology. Dyrk1A decreased axon growth, Dyrk3 and Dyrk4
      increased dendritic branching, and Dyrk2 decreased both axon and dendrite growth
      and branching. Kinase-deficient mutants revealed that most of these effects
      depend on kinase activity. Because doublecortin (DCX), a microtubule-binding
      protein, regulates cytoskeletal dynamics and neuronal morphogenesis, we
      investigated the possibility that DCX is a target of Dyrks. We found that
      overexpression of Dyrk2 and Dyrk3, but not Dyrk1A or Dyrk4, can change DCX
      phosphorylation status. Mutation of a consensus phosphorylation site for Dyrk
      kinases at Serine 306 (Ser306) in DCX indicated that this is one target site for
      Dyrk2 and Dyrk3. Overexpression of Dyrk2 restored altered DCX distribution in the
      growth cones of dendrites and axons, and partially reversed the morphological
      effects of DCX overexpression; some of these effects were abrogated by mutation
      of Ser306 to alanine. These studies implicate Dyrks in the regulation of
      cytoskeletal organization and process outgrowth in neurons, and suggest that DCX
      is one relevant Dyrk target.

PMID- 22359284
TI  - Epigenetic markers of early tumor development.
AB  - Cancer patients' outcome and survival depends on the early diagnosis of malignant
      lesions. Several investigation methods used for the prevention and early
      detection strategies have specific limitations. More recently, epigenetic changes
      have been considered one of the most promising tools for the early diagnosis of
      cancer. Some of these epigenetic alterations including promoter hypermethylation
      of genes like P16INK4a, BRCA1, BRCA2, ERalpha and RARbeta2, APC, and RASSF1A have
      been associated with early stages of mammary gland tumorigenesis and have been
      suggested to be included in the models that evaluate individual breast cancer
      risk. In lung cancer, P16INK4a and MGMT gene hypermethylation was observed in
      sputum years before clinical manifestation of the squamous cell carcinoma among
      smokers. Loss of GSTP1 function by DNA hypermethylation together with changes in
      the methylation levels of repetitive elements like LINE-1 and Sat2 was reported
      in prostatic preneoplastic lesions. Also, DNA hypermethylation for hMLH1 and MGMT
      DNA repair genes was reported in precursor lesions to colorectal cancer. These
      epigenetic alterations may be influenced by factors such as xenoestrogens,
      folate, and multivitamins. Detection of these changes may help determining cancer
      susceptibility and early diagnosis.

PMID- 22359285
TI  - Epigenetics of solid cancer stem cells.
AB  - Epigenetics is an emerging science that can help to explain carcinogenesis. The
      possibility that carcinogenesis may originate in a stem cell process was proposed
      recently. Stem cells are generated and contribute to tumor formation during the
      process of tumor development. This chapter focuses on the role of epigenetics and
      genetics in stem cell formation, different theories about the origin of cancer
      stem cells (CSCs), and epigenetic mechanisms that occur in solid CSCs. Potential
      applications of knowledge gained through this field and future prospects for
      cancer treatment also are discussed.

PMID- 22359286
TI  - DNA methylation and histone modifications in breast cancer.
AB  - Breast cancer is caused by progressive genetic alterations and epigenetic changes
      that trigger tumor development. Among the epigenetic alterations descried in
      breast cancer, DNA promoter methylation has been extensively studied and observed
      in genes involved in several critical signaling pathways that initiate and
      promote breast tumorigenesis. In addition to DNA hypermethylation, global
      methylation levels have been observed to decrease with breast cancer progression.
      In close connection with DNA methylation changes, histone modifications,
      especially the acetylation and methylation of histone lysines, play an essential
      role in the nucleosomes remodeling and gene expression regulation in breast
      cancer.

PMID- 22359287
TI  - DNA methylation changes in prostate cancer.
AB  - Epigenetic alterations contribute significantly to the development and
      progression of prostate cancer, the most prevalent malignant tumor in males of
      Western industrialized countries. Here, we review recent research on DNA
      methylation alterations in this cancer type. Hypermethylation of several genes
      including GSTP1 is well known to occur in a consistent and apparently coordinate
      fashion during the transition from intraepithelial neoplasia to frank carcinoma.
      These hypermethylation events have shown promise as biomarkers for detection of
      prostate carcinoma. Many other individual genes have been shown to undergo
      hypermethylation, which is typically associated with diminished expression. These
      investigations indicate additional candidates for biomarkers; in particular,
      hypermethylation events associated with progression can be employed to identify
      more aggressive cases. In addition, some of genes silenced by aberrant
      methylation in prostate have been shown to exhibit properties of tumor
      suppressors, revealing insights into mechanisms of carcinogenesis. Whereas most
      studies in the past have used candidate gene approaches, new techniques allowing
      genome-wide screening for altered methylation are increasingly employed in
      prostate cancer research and have already yielded encouraging results.

PMID- 22359289
TI  - Epigenetics of bladder cancer.
AB  - Epigenetic changes are closely associated with tumor development and prognosis of
      bladder cancer, and its detection in specimens (tissue/body fluid) may be
      feasible and more sensitive than conventional methods. Additionally, the
      epigenetic changes are interesting from a clinical point of view because it may
      be possible to reverse epigenetic changes and restore the gene function.
      Epigenetic markers might therefore be more useful than conventional molecular
      markers for the detection, prediction of prognosis, and treatment of bladder
      cancer.

PMID- 22359290
TI  - Epigenetics in myeloid malignancies.
AB  - Myeloid hematological malignancies are among the epigenetically best
      characterized neoplasms. The comparatively low number of recurring balanced and
      unbalanced chromosomal abnormalities as well as common genetic mutations has
      enabled scientists to relate epigenetic states to these. The ease of accessing
      malignant cells through bone marrow aspiration has certainly contributed to the
      fast expansion of knowledge. Even so, the clinical and pathogenetic relevance of
      epigenetic changes is still not known, and the field will certainly evolve very
      fast with the development of new analytic techniques. The first example of
      successful epigenetic therapy is seen in myeloid malignancies, in the high-risk
      myelodysplastic syndromes (MDS) which are routinely treated with the
      demethylating agent azacytidine.This chapter will concentrate on describing the
      epigenetic changes in acute myeloid leukemia (AML), chronic myeloid leukemia
      (CML) and MDS. An overview of clinical relevance and epigenetic therapeutic
      approaches is also made.

PMID- 22359291
TI  - The epigenetics of brain tumors.
AB  - Glioblastoma, medulloblastoma, and ependymoma represent molecularly and
      clinically diverse forms of adult and pediatric brain tumors. While each tumor
      displays genetic, transcriptional, and cytogenetic heterogeneity, the epigenome
      of these tumors has only recently emerged as a major field of interest. Here, we
      describe advances in our understanding of the epigenetics of brain tumors,
      focusing on DNA methylation, histone modifications, and microRNA deregulation
      which contribute to the pathogenesis of these diseases.

PMID- 22359292
TI  - DNA methylation changes in cervical cancers.
AB  - Cervical carcinoma is one of the major causes of death in women worldwide. It is
      difficult to foresee a dramatic increase in cure rate even with the most optimal
      combination of cytotoxic drugs, surgery, and radiation; therefore, testing of
      molecular targeted therapies against this malignancy is highly desirable.
      Cervical cancer is a multistep process with accumulation of genetic and
      epigenetic alterations in regulatory genes, leading to activation of oncogenes
      and inactivation or loss of tumor suppressor genes (TSGs). In the last decade, in
      addition to genetic alterations, epigenetic inactivation of TSGs by promoter
      hypermethylation has been recognized as an important and alternative mechanism in
      tumorigenesis. In cervical cancer, epigenetic alterations can affect the
      expression of papillomavirus as well as host genes in relation to stages
      representing the multistep process of carcinogenesis. Here we discuss these
      epigenetic alterations in cervical cancer focusing on DNA methylation.

PMID- 22359293
TI  - Epigenetics of colon cancer.
AB  - Accumulation of genetic and epigenetic alterations transforms normal colonic
      epithelial cells to adenocarcinoma cells. Genetic alterations include mutations
      in tumor suppressor genes and oncogenes, whereas epigenetic mechanisms are
      defined as heritable alterations in gene expression that is independent of
      changes in the primary DNA sequence. Role of epigenetic mechanisms in development
      and maintenance of organ- and tissue-specific gene expression is now realized.
      Disturbances in epigenetic landscape can lead to malignant cellular makeover, and
      these heritable changes are maintained through various cycles of cell division
      that renders cells to have discrete identity with similar genetic information.
      Epigenetic alterations in colorectal cancer (CRC) that transform colonic
      epithelial cells into adenocarcinoma cells include aberrant DNA methylation,
      chromatin modifications, and noncoding RNAs, especially microRNA expression. CpG
      island DNA methylation and aberrant methylation of genes drive the initiation and
      progression of CRC. Histone modifications impinge on chromatin structure and gene
      expression and thus play an important role in gene silencing in CRC. DNA
      hypermethylation also leads to downregulation and inappropriate expression of
      certain microRNAs that act like tumor suppressor genes. Determining the causes
      and roles of epigenetic instability in CRC pathogenesis will lead to effective
      prevention and therapeutic strategies for patients with CRC. Epigenetic drugs
      that underscore the reversible nature of epigenetic events have led the
      possibility of epigenetic therapy as a treatment option in CRC.

PMID- 22359288
TI  - DNA methylation in promoter region as biomarkers in prostate cancer.
AB  - The prostate gland is the most common site of cancer and the second leading cause
      of cancer death in American men. Recent emerging molecular biological
      technologies help us to know that epigenetic alterations such as DNA methylation
      within the regulatory (promoter) regions of genes are associated with
      transcriptional silencing in cancer. Promoter hypermethylation of critical
      pathway genes could be potential biomarkers and therapeutic targets for prostate
      cancer. In this chapter, we updated current information on methylated genes
      associated with the development and progression of prostate cancer. Over 40 genes
      have been investigated for methylation in promoter region in prostate cancer.
      These methylated genes are involved in critical pathways, such as DNA repair,
      metabolism, and invasion/metastasis. The role of hypermethylated genes in
      regulation of critical pathways in prostate cancer is discussed. These findings
      may provide new information of the pathogenesis, the exciting potential to be
      predictive and to provide personalized treatment of prostate cancer. Indeed, some
      epigenetic alterations in prostate tumors are being translated into clinical
      practice for therapeutic use.

PMID- 22359295
TI  - Epigenome and DNA methylation in oral squamous cell carcinoma.
AB  - Epigenetics studies and defines inherited changes in gene expression that are not
      encoded in the DNA sequence. The most studied epigenetic change in mammalian DNA
      is cytosine methylation in CpG dinucleotide areas. The other main group in
      epigenetic changes includes the posttranslational modifications of histones,
      mainly phosphorylation, deacetylation changes, and in the ubiquitinylation
      status. Oral squamous cell carcinoma is the most common malignancy of the oral
      cavity, and epigenetic changes are very common, as described in this chapter.
      Alterations in the DNA methylation status resulting from exposure to
      environmental stress agents have been documented even before birth. Although many
      epigenetic markers are potentially reversible, the mechanism still remains
      unclear and many epigenetic changes persist across cell lines and the life of the
      organism.

PMID- 22359294
TI  - Promoter methylation in head and neck tumorigenesis.
AB  - In addition to genetic alterations of gains and losses, epigenetic events of
      promoter methylation appear to further undermine a destabilized genomic
      repertoire in squamous head and neck carcinoma (HNSCC). This chapter provides an
      overview of frequently methylated tumor suppressor genes in benign head and neck
      papillomas, primary HNSCC tumors, and HNSCC cell lines and their relevance as
      epigenetic markers in head and neck tumorigenesis.

PMID- 22359296
TI  - Clinical implications of epigenetic alterations in human thoracic malignancies:
      epigenetic alterations in lung cancer.
AB  - Besides known genetic aberrations, epigenetic alterations have emerged as common
      hallmarks of many cancer types, including lung cancer. Epigenetics is a process
      involved in gene regulation, mediated via DNA methylation, histone modification,
      chromatin remodeling, and functional noncoding RNAs, which influences the
      accessibility of the underlying DNA to transcriptional regulatory factors that
      activate or repress expression. Studies have shown that epigenetic dysregulation
      is associated with multiple steps during carcinogenesis. Since epigenetic therapy
      is now in clinical use in hematopoietic diseases and undergoing trials for lung
      cancer, a better understanding of epigenetic abnormalities is desired. Recent
      technologies for high-throughput genome-wide analyses for epigenetic
      modifications are promising and potent tools for understanding the global
      dysregulation of cancer epigenetics. In this chapter, studies of epigenetic
      abnormality and its clinical implication in lung cancers are discussed.

PMID- 22359297
TI  - The role of microRNAs in the management of liver cancer.
AB  - Four major components of epigenetic regulation are promoter methylation, histone
      modification, chromatin conformation changes, and altered expression of noncoding
      RNAs, especially microRNAs (miRNAs). MiRNAs are noncoding RNAs of single-stranded
      RNA molecules consisting of ~22 nucleotides that regulate gene expression at the
      posttranscriptional level. MiRNAs are endogenous and potentially can regulate
      every aspect of cellular activity, including development and proliferation,
      differentiation, metabolism, viral infection, epigenetic modulation, apoptotic
      cell death, and tumor genesis. Recent studies provide evidence that miRNAs are
      abundant in the liver and affect a diverse spectrum of liver functions. MiRNA
      expression and deregulation of miRNAs may be a major pathogenetic factor in many
      liver diseases. Although global downregulation is a common trait in human
      malignancies, including viral hepatitis, hepatocellular carcinoma, and polycystic
      liver diseases, specific miRNAs are upregulated in cancer and offer new
      diagnostic and therapeutic strategies to manage liver diseases. Here, the current
      status of the role of miRNAs in liver cancer is discussed along with areas for
      future research.

PMID- 22359298
TI  - Epigenetics in ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological cancer. Due to few early symptoms
      and a lack of early detection strategies, most patients are diagnosed with
      advanced-stage disease. Most of these patients, although initially responsive,
      eventually develop drug resistance. In this chapter, epigenetic changes in
      ovarian cancer are described. Various epigenetic changes including CpG island
      methylation and histone modification have been identified in ovarian cancer.
      These aberrations are associated with distinct disease subtypes and present in
      circulating serum of ovarian cancer patients. Several epigenetic changes have
      shown promise for their diagnostic, prognostic, and predictive capacity but still
      need further validation.In contrast to DNA mutations and deletions, epigenetic
      modifications are potentially reversible by epigenetic therapies. Promising
      preclinical studies show epigenetic drugs to enhance gene re-expression and drug
      sensitivity in ovarian cancer cell lines and animal models.

PMID- 22359300
TI  - Detection and analysis of DNA methylation by pyrosequencing.
AB  - Pyrosequencing is a "sequencing by synthesis" technique which can be used to
      quantify DNA methylation at specific CpG sites within the target region of
      interest. Biotin labelled polymerase chain reaction (PCR) products form the
      template for base-pair nucleotide incorporation causing a light emitting cascade
      reaction resulting in the formation of a pyrogram and the calculation of the
      percentage methylation for each site. Prior to pyrosequencing, it is essential to
      bisulphite-convert the DNA sample and then perform locus-specific PCR for the
      region of interest. One of the PCR primers needs to be biotinylated and a
      separate sequencing primer is required for the pyrosequencing itself.

PMID- 22359301
TI  - Screening for miRNA expression changes using quantitative PCR (Q-PCR).
AB  - In this section, we describe the use of Applied Biosystems TaqMan Array microRNA
      Card Set 3.0 to identify miRNA expression in a given RNA sample. This array set
      includes an array "A" and an array "B" which each have 384 wells that contain
      specific forward, reverse, and probe oligoinucleotides for measuring the
      expression of individual miRNAs during a Real-Time PCR (Q-PCR) reaction. Array
      "A" includes assays for profiling the comparatively higher expressed and better
      characterized miRNAs. Presently there are 1,048 mature miRNAs annotated in
      miRBase (release 16). The relatively small amount of miRNAs in comparison to
      protein-coding genes makes this format a viable option for measuring genome-wide
      miRNA expression changes. The Applied Biosystems TaqMan miRNA array set 3.0,
      which includes two separate arrays, can profile 754 miRNAs.

PMID- 22359302
TI  - Genome-wide methylation analysis.
AB  - The disruption and alteration of genomic methylation patterns is a hallmark of
      cancer and other disease states. Understanding and characterizing genome-wide
      methylation will have a profound effect on our understanding of tumorigenesis and
      provide novel avenues for therapy. This chapter serves to describe techniques
      that examine genome-wide methylation patterns including luminometric methylation
      assay, restriction landmark genome scanning, and the cytosine extension assay,
      which utilize methylation-sensitive restriction enzymes. Additional techniques
      such as nucleotide separation assays (nearest neighbor analysis and high
      performance capillary electrophoresis) and the infinium methylation assay are
      discussed. These techniques allow for the determination of changes in global
      methylation levels, as well as regional changes in methylation throughout the
      genome.

PMID- 22359299
TI  - DNA methylation in pancreatic cancer: protocols for the isolation of DNA and
      bisulfite modification.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor and still remains
      a challenge for its lack of effective therapeutic strategies, which is due to the
      late diagnosis of this disease. Methylation markers might improve early detection
      and surveillance of PDAC. Furthermore, analysis of hypermethylation in the tumor
      tissue might help to identify new targets for therapeutic intervention and
      improve the understanding of the pathophysiological changes occurring in
      pancreatic cancer. Methylation specific PCR is the method of choice if a small
      number of genes will be tested in a larger set of patient samples. After DNA
      isolation by standard procedure, the DNA is then modified using sodium bisulfite.
      This DNA can then be used in qualitative and quantitative PCR assays.

PMID- 22359303
TI  - Microarray for epigenetic changes: gene expression arrays.
AB  - Microarrays can be used to examine changes involving all aspects of the
      epigenetic interactions. As the relationship between DNA methylation, histone
      modifications, and gene expression is elucidated, an important aspect to
      investigate is how the epigenetic status regulates the cell through differential
      expression of genes. This can provide data from work including experimental drug
      investigations from cell line models, or more directly patient comparison data.

PMID- 22359304
TI  - Detecting DNA methylation using the methylated CpG island amplification and
      microarray technique.
AB  - Methylated CpG island amplification and microarray (MCAM) is a two-color array
      technique that quantifies DNA methylation by hybridizing equimolar amounts of
      treated vs. control cell-line DNA to an array platform. Sample preparation,
      hybridization, and scanning are performed over 1 week, but multiple samples can
      be prepared simultaneously, allowing for high-throughput processing and data
      acquisition. One microarray slide is required for each sample assayed, with a
      control sample hybridized with each test sample.

PMID- 22359305
TI  - Nutrigenomics: implications for breast and colon cancer prevention.
AB  - Nutrigenomics refers to the interaction between one's diet and his/her genes.
      These interactions can markedly influence digestion, absorption, and the
      elimination of bioactive food components, as well as influence their site of
      actions/molecular targets. Nutrigenomics comprises nutrigenetics, epigenetics,
      and transcriptomics, coupled with other "omic," such as proteomics and
      metabolomics, that apparently account for the wide variability in cancer risk
      among individuals with similar dietary habits. Multiple food components including
      essential nutrients, phytochemical, zoochemicals, fungochemical, and
      bacterochemicals have been implicated in cancer risk and tumor behavior,
      admittedly with mixed results. Such findings suggest that not all individuals
      respond identically to a diet. This chapter highlights the influence of single
      nucleotide polymorphism, copy number, epigenetic events, and transcriptomic
      homeostasis as factors influencing the response to food components and ultimately
      health, including cancer risk. Both breast and colorectal cancers are reviewed as
      examples about how nutrigenomics may influence the response to dietary intakes.
      As the concept that "one size fits all" comes to an end and personalized
      approaches surface, additional research data will be required to identify those
      who will benefit most from dietary change and any who might be placed at risk
      because of an adjustment.

PMID- 22359306
TI  - Dietary and lifestyle factors of DNA methylation.
AB  - Lifestyle factors, such as diet, smoking, physical activity, and body weight
      management, are known to constitute the majority of cancer causes. Epigenetics
      has been widely proposed as a main mechanism that mediates the reversible effects
      of dietary and lifestyle factors on carcinogenesis. This chapter reviews human
      studies on potential dietary and lifestyle determinants of DNA methylation. Apart
      from a few prospective investigations and interventions of limited size and
      duration, evidence mostly comes from cross-sectional observational studies and
      supports some associations. Studies to date suggest that certain dietary
      components may alter genomic and gene-specific DNA methylation levels in systemic
      and target tissues, affecting genomic stability and transcription of tumor
      suppressors and oncogenes. Most data and supportive evidence exist for folate, a
      key nutritional factor in one-carbon metabolism that supplies the methyl units
      for DNA methylation. Other candidate bioactive food components include alcohol
      and other key nutritional factors of one-carbon metabolism, polyphenols and
      flavonoids in green tea, phytoestrogen, and lycopene. Some data also support a
      link of DNA methylation with physical activity and energy balance. Effects of
      dietary and lifestyle exposures on DNA methylation may be additionally modified
      by common genetic variants, environmental carcinogens, and infectious agents, an
      aspect that remains largely unexplored. In addition, growing literature supports
      that the environmental conditions during critical developmental stages may
      influence later risk of metabolic disorders in part through persistent
      programming of DNA methylation. Further research of these modifiable determinants
      of DNA methylation will improve our understanding of cancer etiology and may
      present certain DNA methylation markers as attractive surrogate endpoints for
      prevention research. Considering the plasticity of epigenetic marks and
      correlated nature of lifestyle factors, more longitudinal studies of healthy
      individuals of varying age, sex, and ethnic groups are warranted, ideally with
      comprehensive data collection on various lifestyle factors.

PMID- 22359307
TI  - Diet, epigenetics, and cancer.
AB  - Cancer encompasses a highly heterogeneous group of diseases. It has been thought
      that transition from promotion to progression in carcinogenesis may be driven
      primarily by epigenetic abnormalities. Diet is known to play crucial roles in
      cancer etiology and has an important role in epigenetics. Current knowledge in
      the interrelationship among cancer, nutrition and epigenetics is reviewed.

PMID- 22359308
TI  - Role of epigenetics in cancer health disparities.
AB  - Cancer disparities in incidence and death rates exist among various racial and
      ethnic groups. These disparities are thought to be due to socioeconomic status,
      culture, diet, stress, the environment, and biology. Biological functions, such
      as epigenetic processes, are affected by all these causal factors and extend
      throughout the life course. Epigenetic processes, in particular DNA methylation,
      may play a role in the induction of phenotypes with increased cancer risk due to
      exposure to these multiple factors. DNA methylation is known to cause changes in
      gene expression of key regulatory genes in cancer. There are limited studies in
      which epigenetic changes have been explored to address cancer disparities in
      various racial and ethnic populations. These few studies have reported
      significant epigenetic differences in various racial and ethnic groups that could
      account for the differences seen in tumor initiation, progression,
      aggressiveness, and outcome of these cancers. Genes differentially methylated
      among these racially and ethnically diverse populations were involved in
      important cellular functions, such as tumor growth, tumor suppression, hormone
      receptors, and genes involved in tumor metastasis. Epigenetic research with the
      advancement in technology has helped identify biomarkers, therapeutic targets,
      and understand cancer causation in the general population. Unfortunately, these
      advances in technology have not been applied to explore the basis for cancer
      health disparities. More research in epigenetics is needed that will enhance our
      understanding of the determinants of cancer across various diverse populations
      and ultimately reduce cancer health disparities.

PMID- 22359310
TI  - Epigenetic epidemiology for cancer risk: harnessing germline epigenetic
      variation.
AB  - Genetic epidemiology aims to use the natural variation in the genome, namely
      single nucleotide polymorphisms and copy number variants to look for associations
      between particular genotypes and disease risk or prognosis. Recent work is now
      aiming to look further into the genome at the natural variation present in the
      epigenome, in DNA methylation as well as histone modifications, which both
      regulate gene expression. Epigenetic epidemiology aims to address the same
      questions about disease risk and prognosis using the normal epigenetic
      variability. Some examples of rare "epimutations" that can be detected in
      peripheral blood DNA have been reported in the genes MLH1, MSH2 and IGF2. Other
      studies have reported increased cancer risk with skewed distributions of the
      normal pattern in cancer cases compared to controls, showing the promise of
      harnessing the normal variation in the epigenome. However, some confounding
      factors need to be considered including the relationship between the epigenome
      and increasing age and tissue heterogeneity. Future studies using genome-wide
      approaches will likely find many more novel epigenetic biomarkers for cancer risk
      and prognosis.

PMID- 22359311
TI  - Epigenetic biomarkers in cancer epidemiology.
AB  - Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify
      people at high risk for developing cancer. In cancer epidemiology, epigenetic
      biomarkers offer advantages over other types of biomarkers because they are
      expressed against a person's genetic background and environmental exposure, and
      because epigenetic events occur early in cancer development. This chapter
      describes epigenetic biomarkers that are being used to study the epidemiology of
      different types of cancer. Because epigenetic alterations can be reversed by
      chemicals and activate gene expression, epigenetic biomarkers potentially have
      numerous clinical applications in cancer intervention and treatment and
      significant implications in public health. This review discusses cancer
      biomarkers, the characteristics of an ideal biomarker for cancer, and
      technologies for biomarker detection.

PMID- 22359312
TI  - A convenient synthesis and a NMR study of the diammoniate of diborane.
AB  - DADB synthesis: The diammoniate of diborane (DADB) was synthesized in a new
      metathesis reaction between the diammoniate of monochloroborane and potassium
      borohydride in liquid ammonia. (1)H and (11)B NMR spectra of DADB are reported.
      The stability in THF was examined by variable-temperature (11)B NMR spectroscopy.

PMID- 22359314
TI  - A multicenter study of pandemic influenza A (H1N1) infection in patients with
      solid tumors in 3 countries: early therapy improves outcomes.
AB  - BACKGROUND: Pandemic influenza A (hereafter 2009/H1N1) caused significant
      morbidity and mortality during the 2009 pandemia. Patients with chronic medical
      conditions and immunosuppressive diseases had a greater risk of complications.
      However, data regarding the characteristics and outcome of 2009/H1N1 infection in
      patients with solid tumors are nonexistent. Herein, the authors describe a series
      of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer
      hospitals worldwide. METHODS: The authors retrospectively reviewed the records of
      patients with solid organ malignancies and 2009/H1N1 from The University of Texas
      M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer
      Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman,
      Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease
      characteristics, and outcome were extracted. RESULTS: In total, 115 cases were
      identified during the pandemic influenza among the 3 institutions. High rates of
      hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients
      who developed pneumonia and those who died were moderately to severely
      immunocompromised (P = .001 and P = .006, respectively). A multivariate competing
      risk analysis demonstrated that a delay >48 hours in starting antiviral therapy
      was associated significantly with an increased risk of developing pneumonia (P =
      .013). CONCLUSIONS: The 2009/H1N1 pandemic caused severe illness in
      immunocompromised patients with cancer who had solid tumors, and heavily
      immunosuppressed patients were at greater risk of developing pneumonia and death.
      Early initiation of antiviral therapy is crucial in this patient population to
      decrease morbidity and probably mortality.

PMID- 22359313
TI  - Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in
      children and young adults: preliminary results from the prospective, multicenter
      study NPC-2003-GPOH/DCOG.
AB  - BACKGROUND: The authors report preliminary results from a prospective multicenter
      study (Nasopharyngeal Carcinoma [NPC] 2003 German Society of Pediatric Oncology
      and Hematology/German Children's Oncology Group [NPC-2003-GPOH/DCOG]). METHODS:
      From 2003 to 2010, 45 patients (ages 8-20 years), including 1 patient with stage
      II NPC and 44 patients with stage III/IV NPC, were recruited to the study. The
      patient with stage II disease received radiotherapy (59.4 grays [Gy]). The
      patients with stage III/IV disease received 3 courses of neoadjuvant chemotherapy
      with cisplatin, 5-fluorouracil, and folinic acid. The cumulative irradiation dose
      was 54 Gy in 5 patients, who achieved complete remission after neoadjuvant
      chemotherapy, and 59.4 Gy in the remaining 40 patients. All patients received
      concomitant cisplatin during the first week and last week of irradiation. After
      irradiation, all patients received interferon beta for 6 months. Tumor response
      was evaluated by magnetic resonance imaging studies and positron emission
      tomography scans. RESULTS: After the completion of treatment, 43 of 45 patients
      were in complete remission. In 2 patients, only a partial response was achieved,
      followed by distant metastases (1 patient) or local progression and distant
      metastases (1 patient), 6 months and 10 months after diagnosis, respectively.
      Another patient developed a solitary pelvic bone metastasis 21 months after
      diagnosis. After a median follow-up of 30 months (range, 6-95 months), the event
      free survival rate was 92.4%, and the overall survival was 97.1%. Acute toxicity
      consisted mainly of leucopenia, mucositis, and nausea; and late toxicity
      consisted of hearing loss and hypothyroidism. CONCLUSIONS: Combined therapy with
      neoadjuvant chemotherapy, radiochemotherapy, and interferon beta was well
      tolerated and resulted in a very good outcome that was superior to the outcomes
      of published results from all other pediatric NPC study groups.

PMID- 22359309
TI  - Multifactorial etiology of gastric cancer.
AB  - The prevalence of gastric cancer is associated with several factors including
      geographical location, diet, and genetic background of the host. However, it is
      evident that infection with Helicobacter pylori (H. pylori) is crucial for the
      development of the disease. Virulence of the bacteria is also important in
      modulating the risk of the disease. After infection, H. pylori gains access to
      the gastric mucosa and triggers the production of cytokines that promote
      recruitment of inflammatory cells, probably involved in tissue damage. Once the
      infection is established, a cascade of inflammatory steps associated with changes
      in the gastric epithelia that may lead to cancer is triggered. H. pylori-induced
      gastritis and H. pylori-associated gastric cancer have been the focus of
      extensive research aiming to discover the underlying mechanisms of gastric tissue
      damage. This research has led to the association of host genetic components with
      the risk of the disease. Among these is the presence of single nucleotide
      polymorphisms (SNPs) in several genes, including cytokine genes, which are able
      to differentially modulate the production of inflammatory cytokines and then
      modulate the risk of gastric cancer. Interestingly, the frequency of some of
      these SNPs is different among populations and may serve as a predictive factor
      for gastric cancer risk within that specific population. However, the role played
      by other genetic modifications should not be minimized. Methylation of gene
      promoters has been recognized as a major mechanism of gene expression regulation
      without changing the primary structure of the DNA. Most DNA methylation occurs in
      cytosine residues in CpG dinucleotide, but it can also be found in other DNA
      bases. DNA methyltransferases add methyl groups to the CpG dinucleotide, and when
      this methylation level is too high, the gene expression is turned off. In H.
      pylori infection as well as in gastric cancer, hypermethylation of promoters of
      genes involved in cell cycle control, metabolism of essential nutrients, and
      production of inflammatory mediators, among others, has been described.
      Interestingly, DNA changes like SNPs or mutations can create CpG sites in
      sequences where transcription factors normally sit, affecting transcription.In
      this chapter, we review the literature about the role of SNPs and methylation on
      H. pylori infection and gastric cancer, with big emphasis to the H. pylori role
      in the development of the disease due to the strong association between both.

PMID- 22359315
TI  - Sensitive and high-throughput isolation of rare cells from peripheral blood with
      ensemble-decision aliquot ranking.

PMID- 22359316
TI  - Interpersonal psychotherapy: evaluation, support, triage.
AB  - Depression is highly prevalent and debilitating among medically ill patients. As
      high as one third of the primary practise patients screen positive for depression
      symptoms and over half of the patients diagnosed with major depressive disorder
      are treated in primary care. However, current primary care service arrangements
      do not efficiently triage patients who screen positive for depression into
      appropriate treatments that reflect their individual needs and preferences. In
      this paper, we describe a tool that aims to fill the gap between screening the
      patients for depression and triaging them to appropriate care. This is a three
      session adaptation of interpersonal psychotherapy: ipt; evaluation, support,
      triage (IPT-EST). We first outline IPT-EST procedures that aim to provide
      structure and content to primary care practitioners who identify patients with
      positive depression symptoms, thus assisting the practitioners to explore the
      patients' psychosocial triggers of depression, give basic strategies to manage
      these interpersonal stressors and provide decisions tools about triaging patients
      with severe/persistent depression into appropriate treatment.

PMID- 22359317
TI  - Purification and characterization of a highly thermostable esterase from the
      actinobacterium Geodermatophilus obscurus strain G20.
AB  - Intracellular thermostable esterase produced by the extremophilic
      Geodermatophilus obscurus G20 was purified to homogeneity by a heat treatment,
      followed by an anion-exchange chromatography, and then characterized. The
      molecular weight of the purified enzyme determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) was shown to be approximatively 55
      kDa. The enzyme showed an optimal activity between pH 8.0 and 9.0 and was stable
      in the pH range 7.0-10.0. Moreover, it is highly thermostable, with a residual
      activity greater than 90% after incubation at 80  degrees C for more than 10 h.
      The enzyme showed preference for esters of p -nitrophenol with short chain fatty
      acid. When the p -nitrophenyl acetate (C2) was used as substrate, the Michaelis
      Menten constant (K(m) ) and maximum velocity for the reaction (V(max) ) of
      esterase were 400 MUM and 2500 U/mg protein, respectively. The effect of
      phenylmethanesulphonyl fluoride (PMSF), a serine-specific inhibitor, on the
      enzyme activity suggested that the thermostable esterase belong to the serine
      hydrolase group. Because of its high thermostability, activity at alkaline pH,
      tolerance to methanol and various metal ions and specificity for short chain
      fatty acids, this enzyme showed high potential for use in biocatalysis. ((c) 2012
      WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

PMID- 22359318
TI  - Comparative analysis of Campylobacter lari cytolethal distending toxin (CDT)
      effect on HeLa cells.
AB  - We aimed to clarify if Campylobacter lari exerts a cytolethal distending toxin
      (CDT) effect on HeLa cells. Campylobacter cell lysates (CCLys) from C. jejuni 81
      176 and urease-positive thermophilic Campylobacter (UPTC) CF89-12 and UPTC
      NCTC12893 isolates were shown to exert a CDT effect on HeLa cells with
      morphological changes examined by Giemsa staining and microscopy. However,
      Campylobacter lari JCM2530(T) isolate showed no effect. In addition,
      Campylobacter cell culture supernatant wash gave low or absent toxic effects with
      both C. jejuni and C. lari organisms. When western blot analysis was carried out
      to clarify if there was a CDTB effect in the CCLys and soluble fractions from
      Campylobacter isolates, which had a CDT effect on HeLa cells or did not have any
      effect, anti-recombinant CjCDTB antibodies identified an immunoreactively
      positive signal at around approximately 25 kDa on all the C. lari isolates
      examined, as well as the C. jejuni 81116 strain. Thus, all the Campylobacter
      isolates including those without any CDT effect were shown to express CDTB at the
      translational level.

PMID- 22359319
TI  - The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic
      variant and risk of pancreatic cancer.
AB  - BACKGROUND: Antitumor T lymphocytes play an essential part in immune surveillance
      of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a
      negative regulator of T cell activation and proliferation and therefore
      influences immune surveillance of carcinogenesis of pancreas. Thus, this study
      examined the association between functional CTLA-4 49G-to-A (49G>A) single
      nucleotide polymorphism and pancreatic cancer risk. METHODS: Genotypes were
      determined in 368 patients with pancreatic cancer and 926 controls, and odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic
      regression. RESULTS: A significant increased risk of pancreatic cancer was found
      to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared
      with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA
      carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 * 10(-5) ) or 2.54 (95% CI = 1.67
      3.87, P = 1.36 * 10(-5) ), respectively. In stratified analyses, the association
      was more pronounced in GA and AA carriers aged <=60 years (OR = 3.10, 95% CI =
      2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92,
      95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes
      (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG
      carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA
      genotype and smoking plus drinking was also evident in intensifying risk of
      pancreatic cancer (P(interaction) = 5.64 * 10(-12) ). CONCLUSIONS: These results
      suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to
      developing pancreatic cancer, alone and in a gene-environment interaction manner.

PMID- 22359320
TI  - Multiple imputation for left-censored biomarker data based on Gibbs sampling
      method.
AB  - Biomarkers, increasingly used in biomedical studies for the diagnosis and
      prognosis of acute and chronic diseases, provide insight into the effectiveness
      of treatments and potential pathways that can be used to guide future treatment
      targets. The measurement of these markers is often limited by the sensitivity of
      the given assay, resulting in data that are censored either at the lower or at
      the upper limit of detection. For the Genetic and Inflammatory Markers of Sepsis
      (GenIMS) study, many different biomarkers were measured to examine the effect of
      different pathways on the development of sepsis. In this study, the left
      censoring of several important inflammatory markers has led to the need for
      statistical methods that can incorporate this censoring into any analysis of the
      biomarker data. This paper focuses on the development of multiple imputation
      methods for the inclusion of multiple left-censored biomarkers in a logistic
      regression analysis. We assume a multivariate normal distribution to account for
      the correlations between biomarkers and use the Gibbs sampler for the estimation
      of the distributional parameters and the imputation of the censored markers. We
      evaluate and compare the proposed methods with some simple imputation methods
      through simulation. We use a data set of inflammatory and coagulation markers
      from the GenIMS study for illustration.

PMID- 22359321
TI  - Probing intermolecular hydrogen bonding in sibenadet hydrochloride polymorphs by
      high-resolution (1) H double-quantum solid-state NMR spectroscopy.
AB  - Molecular packing in two polymorphs of sibenadet hydrochloride (AR-C68397AA,
      ViozanTM) is investigated using a combined experimental (1) H double-quantum (DQ)
      solid-state magic-angle spinning nuclear magnetic resonance and computational
      (gauge including projected augmented wave calculation of chemical shifts)
      approach. For Form I, NH-NH and NH-OH (1) H DQ peaks are observed corresponding
      to nearest distances of 2.62 and 2.87 A, respectively, for the intermolecular
      hydrogen-bonding arrangement in the single-crystal X-ray diffraction structure.
      The same (1) H DQ peaks at the same (1) H chemical shifts are observed for Form
      II, for which there is no single-crystal diffraction structure, indicating the
      same intermolecular hydrogen-bonding arrangement of the benzothiazolone moieties
      as in Form I. (1) H DQ build-up (as a function of the DQ recoupling time) curves
      are presented for the resolved NH-NH and NH-OH DQ peaks for the two polymorphs.
      For Form I, the ratio of the maximum intensity for the NH-OH and NH-NH DQ peaks
      is in excellent agreement with the ratio of the summed squares of the H-H dipolar
      couplings, as determined using H-H distances from the crystal structure up to 4
      A. Small differences in the (1) H DQ build-up behaviour for the two polymorphs
      are attributed to differences in the longer-range NH-OH distances associated with
      different inter-layer arrangements.

PMID- 22359322
TI  - Estimating survival of dental fillings on the basis of interval-censored data and
      multi-state models.
AB  - We aim to compare the life expectancy of a filling in a primary tooth between two
      types of treatments. We define the probabilities that a dental filling survives
      without complication until the permanent tooth erupts from beneath (exfoliation).
      We relate the time to exfoliation of the tooth to the age of the child and the
      time to failure of the filling to the duration since the treatment. We followed
      up fillings at repeated examinations where information is collected regarding the
      filling and the tooth. Several fillings can be placed in the same mouth, possibly
      by the same dentist. To deal with all these particularities, we propose to use a
      parametric four-state model with three random effects to take into account the
      hierarchical cluster structure. For inference, right and interval censoring as
      well as left truncation have to be dealt with. With the proposed approach, we can
      conclude that the estimated probability that a filling survives without
      complication until exfoliation is larger for one treatment than for the other,
      for all ages of the child at the time of treatment.

PMID- 22359323
TI  - Improved sample preparation of glyphosate and methylphosphonic acid by EPA method
      6800A and time-of-flight mass spectrometry using novel solid-phase extraction.
AB  - The employment of chemical weapons by rogue states and/or terrorist organizations
      is an ongoing concern in the United States. The quantitative analysis of nerve
      agents must be rapid and reliable for use in the private and public sectors.
      Current methods describe a tedious and time-consuming derivatization for gas
      chromatography-mass spectrometry and liquid chromatography in tandem with mass
      spectrometry. Two solid-phase extraction (SPE) techniques for the analysis of
      glyphosate and methylphosphonic acid are described with the utilization of
      isotopically enriched analytes for quantitation via atmospheric pressure chemical
      ionization-quadrupole time-of-flight mass spectrometry (APCI-Q-TOF-MS) that does
      not require derivatization. Solid-phase extraction-isotope dilution mass
      spectrometry (SPE-IDMS) involves pre-equilibration of a naturally occurring
      sample with an isotopically enriched standard. The second extraction method, i
      Spike, involves loading an isotopically enriched standard onto the SPE column
      before the naturally occurring sample. The sample and the spike are then co
      eluted from the column enabling precise and accurate quantitation via IDMS. The
      SPE methods in conjunction with IDMS eliminate concerns of incomplete elution,
      matrix and sorbent effects, and MS drift. For accurate quantitation with IDMS,
      the isotopic contribution of all atoms in the target molecule must be
      statistically taken into account. This paper describes two newly developed sample
      preparation techniques for the analysis of nerve agent surrogates in drinking
      water as well as statistical probability analysis for proper molecular IDMS. The
      methods described in this paper demonstrate accurate molecular IDMS using APCI-Q
      TOF-MS with limits of quantitation as low as 0.400 mg/kg for glyphosate and 0.031
      mg/kg for methylphosphonic acid.

PMID- 22359324
TI  - Molecular imaging of drug-eluting coronary stents: method development,
      optimization and selected applications.
AB  - A molecular imaging application was developed to characterize the drug
      distribution on CYPHER(r) and NEVOTM Drug-eluting Stents using MALDI Qq-ToF
      analytical methodology. The coating matrix, laser energy, laser frequency,
      spatial resolution (related to rastering speed) and mass spectrometer parameters
      were optimized to analyze drug distribution in both durable and biodegradable
      polymer matrices. The developed method was extended to generate data from stents
      explanted from porcine coronary arteries. Due to the method's intrinsic
      specificity, it offers a significant advantage over other techniques in that it
      allows low-level detection of the target molecule without biological
      interferences from the blood or tissue. The method is also capable of detecting
      drug-related degradation products both from the finished stent product and from
      explanted stents.

PMID- 22359325
TI  - Formation of oligomeric alkenylperoxides during the oxidation of unsaturated
      fatty acids: an electrospray ionization tandem mass spectrometry study.
AB  - This study reports the identification of oligomeric alkenylperoxides by
      electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry
      (ESI-MS(2)), during the oxidation of oleic, linoleic and linolenic acids with
      Fenton's (Fe(2+)/H(2)O(2)) and Fe(2+)/O(2) systems. The reactions were followed
      by ferrous oxidation-xylenol orange method together with GC-MS and GC-FID,
      allowing to observe that both oxidation systems are different in terms of
      hydroperoxide evolution, probably due to the presence of different intermediate
      reactive species: perferryl ion and OH(.) radical responsible for the
      decomposition of lipid hydroperoxides and formation of new compounds. The
      analysis of ESI-MS in the negative mode, obtained after oxidation of each fatty
      acid, confirmed the presence of the monomeric oxidation products together with
      other compounds at high mass region above m/z 550. These new ions were attributed
      to oligomeric structures, identified by the fragmentation pathways observed in
      the tandem mass spectra.

PMID- 22359326
TI  - Charge and substituent effects on the stability of porphyrin/G-quadruplex
      adducts.
AB  - The adduct ions of two tetramolecular G-quadruplexes formed from the d(TGGGGT)
      and d(TTGGGGGT) single strands with a group of cationic porphyrins, with
      different charges and substituents, and one neutral porphyrin, were investigated
      by ESI-MS and ESI-MS/MS in the negative ion mode. Formation of [Q +
      nNH(4)(+)+P(p+)-(z + n + p)H(+)](z-) adduct ions (where Q = quadruplex, n =
      number of quartets minus 1, P = porphyrin and p(+) = 0,1,2,3,4) indicates that
      the porphyrins are bound outside the quadruplexes providing an additional
      stabilization to those structures. The fragmentation pathways of the [Q +
      nNH(4)(+)+P(p+)-(z + n + p)H(+)](z-) adduct ions depend on the number of positive
      charges (p(+)) of the porphyrins and on the overall complex charge (z(-)), but do
      not show a significant dependence on the type of the substituent groups in the
      porphyrins. Formation of the 'unfilled' ions [Q + P(p+)-(z + p)H(+)](z-)
      predominates for porphyrins with a higher number of positive charges. Strand
      separation with the formation of [T + P(p+)-(z-2 + p)H(+)]((z-2)-) and (SS
      2H(+))(2-) ions, where T = [d(TG(4)T)](3) and [d(T(2)G(5)T)](3) and SS =
      d(TG(4)T) and d(T(2)G(5)T) is only observed for the complexes with a higher
      overall negative charge. Porphyrin loss with the formation of [Q + nNH(4)(+)-(z +
      n)H(+)](z-) ions occurs predominantly for the neutral and monocharged porphyrins.
      The predominant formation of the 'unfilled' ions, [Q + P(p+)-(z + n)H(+)](z-),
      for porphyrins with a higher number of charges shows that these porphyrins can
      prevent strand separation and preserve, at least partially, the quadruplex
      structure.

PMID- 22359327
TI  - Mass spectrometric characterization of phosphorylated peptides using MALDI in
      source decay via redox reactions.
AB  - Matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) has been
      used for characterization of a phosphorylated peptides and proteins because
      labile phosphate group is not lost during the MALDI-ISD process. The conventional
      MALDI-ISD is initiated by the hydrogen transfer from reducing matrix molecules to
      peptide backbone, leading to c'- and z'-series ions. In contrast, when an
      oxidizing chemical 5-nitrosalicylic acid (5-NSA) is served as the MALDI-ISD
      matrix, a- and x-series ions are specifically generated by hydrogen abstraction
      from peptide backbone to matrix molecule. The 5-NSA provides useful complementary
      information to the conventional MALDI-ISD for the analysis of amino acid
      sequencing and site localization of phosphorylation in peptides. The MALDI-ISD
      with reducing and oxidizing matrix could be a useful method for the de novo
      peptide sequencing.

PMID- 22359329
TI  - Identification and structural characterization of the synthetic cannabinoid 3-(1
      adamantoyl)-1-pentylindole as an additive in 'herbal incense'.
AB  - Since the end of 2010, more than 20 synthetic cannabimimetics have been
      identified in 'Spice' products, demonstrating the enormous dynamic in this field.
      In an effort to cope with the problem, many countries have already undertaken
      legal measures by putting some of these compounds under control. Nevertheless,
      once a number of compounds were scheduled, they were soon replaced by other
      synthetic cannabinoids. In this article, we report the identification of a new-
      and due to its substitution pattern rather uncommon--cannabimimetic found in
      several 'herbal incense' products. The GC-EI mass spectrum first led to
      misidentification as the alpha-methyl-derivative of JWH-250. However, since both
      substances show different retention indices, thin-layer chromatography was used
      to isolate the unknown compound. After application of nuclear magnetic resonance
      spectroscopy, high-resolution MS and GC-MS/MS techniques, the compound was
      identified as 3-(1-adamantoyl)-1-pentylindole, a derivative of JWH-018 carrying
      an adamantoyl moiety instead of a naphthoyl group. This finding supports that the
      listing of synthetic cannabinoids as prohibited substances triggers the
      appearance of compounds with uncommon substituents. Moreover, it emphasizes the
      necessity of being aware of the risk of misidentification when using techniques
      sometimes providing only limited structural information like GC-MS.

PMID- 22359328
TI  - Evaluation of protein quantification using standard peptides containing single
      conservative amino acid replacements.
AB  - Structural analogs are evaluated as peptide internal standards for protein
      quantification with liquid chromatography-multiple reaction monitoring mass
      spectrometry (LC-MRM); specifically, single conservative amino acid replacements
      (SCAR) are performed to create tagged standards that differ by the addition or
      subtraction of a single methylene group in one amino acid side chain. Because the
      performance of stable isotope-labeled standards (SIS) has been shown to be
      superior to structural analogs, differences in both development and quantitative
      performance between assays based on SIS and SCAR peptides are explored. To
      establish an assay using the structural analogs, analysis of endogenous, SCAR and
      SIS peptides was performed to examine their ion signal, fragmentation patterns
      and response in LC-MRM. Performance of SCAR and SIS peptides was compared for
      quantification of epidermal growth factor receptor from lung cancer cell lysates
      and immunoglobulin M in the serum of multiple myeloma patients.

PMID- 22359330
TI  - Gas-flow assisted ion transfer for mass spectrometry.
AB  - Methods and devices that use gas flows to collect ions and transfer them over
      long distances for mass spectrometric analysis have been developed. Gas flows
      derived from the ionization source itself or provided by means of additional
      pumping were used to generate a laminar flow inside cylindrical tube.
      Hydrodynamic simulations and experimental tests demonstrate that laminar flow can
      transfer ions over long distance. The typical angular discrimination effects
      encountered when sampling ions from ambient ionization sources are minimized, and
      the sampling of relatively large surface areas is demonstrated with desorption
      electrospray ionization (DESI). Ion transfer over 6 m has been achieved and its
      application to multiplexed chemical analysis is demonstrated on samples at
      locations remote from the mass spectrometer.

PMID- 22359331
TI  - Gas-phase doubly charged complexes of cyclic peptides with copper in +1, +2 and
      +3 formal oxidation states: formation, structures and electron capture
      dissociation.
AB  - Copper complexes with a cyclic D-His-beta-Ala-L-His-L-Lys and all-L-His-beta-Ala
      His-Lys peptides were generated by electrospray which were doubly charged ions
      that had different formal oxidation states of Cu(I), Cu(II) and Cu(III) and
      different protonation states of the peptide ligands. Electron capture
      dissociation showed no substantial differences between the D-His and L-His
      complexes. All complexes underwent peptide cross-ring cleavages upon electron
      capture. The modes of ring cleavage depended on the formal oxidation state of the
      Cu ion and peptide protonation. Density functional theory (DFT) calculations,
      using the B3LYP with an effective core potential at Cu and M06-2X functionals,
      identified several precursor ion structures in which the Cu ion was
      threecoordinated to pentacoordinated by the His and Lys side-chain groups and the
      peptide amide or enolimine groups. The electronic structure of the formally
      Cu(III) complexes pointed to an effective Cu(I) oxidation state with the other
      charge residing in the peptide ligand. The relative energies of isomeric
      complexes of the [Cu(c-HAHK + H)](2+) and [Cu(c-HAHK - H)](2+) type with closed
      electronic shells followed similar orders when treated by the B3LYP and M06-2X
      functionals. Large differences between relative energies calculated by these
      methods were obtained for open-shell complexes of the [Cu(c-HAHK)](2+) type.
      Charge reduction resulted in lowering the coordination numbers for some Cu
      complexes that depended on the singlet or triplet spin state being formed. For
      [Cu(c-HAHK - H)](2+) complexes, solution H/D exchange involved only the N-H
      protons, resulting in the exchange of up to seven protons, as established by
      ultra-high mass resolution measurements. Contrasting the experiments, DFT
      calculations found the lowest energy structures for the gas-phase ions that were
      deprotonated at the peptide C(alpha) positions.

PMID- 22359332
TI  - Observation of dimethylaminoethyl methacrylate-myoglobin binding reaction using
      laser spray mass spectrometry.
AB  - Covalent bonds are often created by a reaction between chemicals and protein
      before causing various adverse effects in a cell. Dimethylaminoethyl methacrylate
      (DMAEMA), which has moderate toxicity, causes skin inflammation and throat
      irritation. For this study, we investigated a reaction mechanism between
      myoglobin and (DMAEMA) using a new analytical tool developed at our laboratory:
      laser spray mass spectrometry technique. It was found that initially DMAEMA was
      added to the amino group of protein by the Michael addition mechanism; the added
      DMAEMA was hydrolyzed to methacrylic acid using an autocatalytic system. The
      results of this study indicate the feasibility of the laser spray technique in
      analyses of reaction dynamics.

PMID- 22359333
TI  - The use of mass defect in modern mass spectrometry.
AB  - Mass defect is defined as the difference between a compound's exact mass and its
      nominal mass. This concept has been increasingly used in mass spectrometry over
      the years, mainly due to the growing use of high resolution mass spectrometers
      capable of exact mass measurements in many application areas in analytical and
      bioanalytical chemistry. This article is meant as an introduction to the
      different uses of mass defect in applications using modern MS instrumentation.
      Visualizing complex mass spectra may be simplified with the concept of Kendrick
      mass by plotting nominal mass as a function of Kendrick mass defect, based on
      hydrocarbons subunits, as well as slight variations on this theme. Mass defect
      filtering of complex MS data has been used for selectively detecting compounds of
      interest, including drugs and their metabolites or endogenous compounds such as
      peptides and small molecule metabolites. Several strategies have been applied for
      labeling analytes with reagents containing unique mass defect features, thus
      shifting molecules into a less noisy area in the mass spectrum, thus increasing
      their detectability, especially in the area of proteomics. All these concepts
      will be covered to introduce the interested reader to the plethora of
      possibilities of mass defect analysis of high resolution mass spectra.

PMID- 22359334
TI  - Sucrose cryo-protection facilitates imaging of whole eye sections by MALDI mass
      spectrometry.
AB  - Sucrose is used as a cryo-preservation agent on large mammalian eyes post
      formalin fixation and is shown to reduce freezing artefacts allowing the
      collection of 12-um thick sections from these large aqueous samples. The
      suitability of this technique for use in MALDI imaging experiments is
      demonstrated by the acquisition of the first images of lipid distributions within
      whole sagittal porcine eye sections.

PMID- 22359335
TI  - Detection and quantitation of a pheomelanin component in melanin pigments using
      pyrolysis-gas chromatography/tandem mass spectrometry system with multiple
      reaction monitoring mode.
AB  - Here, we describe the reliable method for the detection and quantitation of a
      pheomelanin component in melanin pigments. Synthetic melanins with various
      contents of pheomelanin-type structural units were thermally degraded, and the
      multiple reaction monitoring mode was applied to detect the pheomelanin markers
      in the pyrolysates by GC/MS/MS. The method allowed the specific detection and
      quantitation of a pheomelanin component in melanin with the incorporation of
      pheomelanin-type units as low as 0.05%. Considering highly universal character of
      the pheomelanin markers, the method could be applied for structural studies of
      natural melanin pigments being mixtures of eumelanin and pheomelanin.

PMID- 22359336
TI  - Qualitative-(semi)quantitative data acquisition of artemisinin and its
      metabolites in rat plasma using an LTQ/Orbitrap mass spectrometer.
AB  - Artemisinin (QHS) is one of the first-line antimalarials, and autoinduction of
      CYP-mediated metabolism can result in its reduced exposure. To better understand
      the autoinduction of QHS, we evaluated the pharmacokinetics of QHS and its phase
      I metabolites in rats using an liquid chromatography-high resolution mass
      spectrometry (LC-HRMS) method. The LC separation was improved, allowing the
      separation of QHS and its metabolites from their diastereomers, and seven
      metabolites of QHS with relatively high exposure were identified in rat plasma,
      including deoxyartemisinin (DQHS), three monoyhydroxylated plus deoxyl
      metabolites (M1-M3) and three monohydroxylated metabolites (M4-M6). For
      detection, a high-resolution LTQ/Orbitrap mass spectrometer with an electrospray
      ionization (ESI) inlet in the positive ion mode was used. High-resolution
      extracted ion chromatograms for each analyte were obtained by processing the full
      scan MS dataset with 10 ppm mass tolerance. The plasma samples were pretreated by
      protein precipitation with acetonitrile. The standard curve was linear (r(2) >
      0.99) over the QHS and DQHS concentration range of 5.0-200.0 ng/ml in 50 ul of
      plasma, which offered sufficient sensitivity and accuracy for the determination
      of QHS and its metabolites. A 3-day validation approach was used for absolute
      quantitation of QHS and DQHS. The other six metabolites of QHS were
      semiquantified based on the calibration curve of QHS. The present method was
      applied to the pharmacokinetic study of QHS in rats after a single oral
      administration. The data shown here also suggest that this type of mass analyzer
      will be capable of a quantitative-qualitative workflow.

PMID- 22359337
TI  - New cathinone-derived designer drugs 3-bromomethcathinone and 3
      fluoromethcathinone: studies on their metabolism in rat urine and human liver
      microsomes using GC-MS and LC-high-resolution MS and their detectability in
      urine.
AB  - 3-Bromomethcathinone (3-BMC) and 3-Fluoromethcathinone (3-FMC) are two new
      designer drugs, which were seized in Israel during 2009 and had also appeared on
      the illicit drug market in Germany. These two compounds were sold via the
      Internet as so-called "bath salts" or "plant feeders." The aim of the present
      study was to identify for the first time the 3-BMC and 3-FMC Phase I and II
      metabolites in rat urine and human liver microsomes using GC-MS and LC-high
      resolution MS (HR-MS) and to test for their detectability by established urine
      screening approaches using GC-MS or LC-MS. Furthermore, the human cytochrome-P450
      (CYP) isoenzymes responsible for the main metabolic steps were studied to
      highlight possible risks of consumption due to drug-drug interaction or genetic
      variations. For the first aim, rat urine samples were extracted after and without
      enzymatic cleavage of conjugates. The metabolites were separated and identified
      by GC-MS and by LC-HR-MS. The main metabolic steps were N-demethylation,
      reduction of the keto group to the corresponding alcohol, hydroxylation of the
      aromatic system and combinations of these steps. The elemental composition of the
      metabolites identified by GC-MS could be confirmed by LC-HR-MS. Furthermore,
      corresponding Phase II metabolites were identified using the LC-HR-MS approach.
      For both compounds, detection in rat urine was possible within the authors'
      systematic toxicological analysis using both GC-MS and LC-MS(n) after a suspected
      recreational users dose. Following CYP enzyme kinetic studies, CYP2B6 was the
      most relevant enzyme for both the N-demethylation of 3-BMC and 3-FMC after in
      vitro-in vivo extrapolation.

PMID- 22359338
TI  - On the inter-instrument and the inter-laboratory transferability of a tandem mass
      spectral reference library. 3. Focus on ion trap and upfront CID.
AB  - Mass spectral libraries represent versatile tools for the identification of small
      bioorganic molecules. Libraries based on electron impact spectra are rated robust
      and transferable. Tandem mass spectral libraries are often considered to work
      properly only on the instrument that has been used to build the library. An
      exception from that rule is the 'Wiley Registry of Tandem Mass Spectral Data,
      MSforID'. In various studies with data sets from different kinds of tandem mass
      spectrometric instruments, the outstanding sensitivity and robustness of this
      tandem mass spectral library search approach was demonstrated. The instrumental
      platforms tested, however, mainly included various tandem-in-space instruments.
      Herein, the results of a multicenter study with a focus on upfront and tandem-in
      time fragmentation are presented. Five laboratories participated and provided
      fragment ion mass spectra from the following types of mass spectrometers: time-of
      flight (TOF), quadrupole-hexapole-TOF, linear ion trap (LIT), 3-D ion trap and
      LIT-Orbitrap. A total number of 1231 fragment ion mass spectra were collected
      from 20 test compounds (amiloride, buphenin, cinchocaine, cyclizine, desipramine,
      dihydroergotamine, dyxirazine, dosulepin, ergotamine, ethambutol, etofylline,
      mefruside, metoclopramide, phenazone, phentermine, phenytoin, sulfamethoxazole,
      sulfamoxole, sulthiame and tetracycline) on seven electrospray ionization
      instruments using 18 different instrumental configurations for fragmentation. For
      1222 spectra (99.3%), the correct compound was retrieved as the best matching
      compound. Classified matches (matches with 'relative average match probability'
      >40.0) were obtained for 1207 spectra (98.1%). This high percentage of correct
      identifications clearly supports the hypothesis that the tandem mass spectral
      library approach tested is a robust and universal identification tool.

PMID- 22359339
TI  - Allelic variation within the putative autism spectrum disorder risk gene homeobox
      A1 and cerebellar maturation in typically developing children and adolescents.
AB  - Homeobox A1 (HOXA1) has been proposed as a candidate gene for autism spectrum
      disorder (ASD) as it regulates embryological patterning of hind-brain structures
      implicated in autism neurobiology. In line with this notion, a nonsynonymous
      single nucleotide polymorphism within a highly conserved domain of HOXA1--A218G
      (rs10951154)--has been linked to both ASD risk, and cross-sectional differences
      in superior posterior lobar cerebellar anatomy in late adulthood. Despite
      evidence for early onset and developmentally dynamic cerebellar involvement in
      ASD, little is known of the relationship between A218G genotype and maturation of
      the cerebellum over early development. We addressed this issue using 296
      longitudinally acquired structural magnetic resonance imaging brain scans from
      116 healthy individuals between 5 and 23 years of age. Mixed models were used to
      compare the relationship between age and semi-automated measures of cerebellar
      volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total
      cerebellar volume increased between ages of 5 and 23 years in both groups.
      However, this was accelerated in the Gcar relative to the AA group (Genotype-by
      age interaction term, P = 0.03), and driven by genotype-dependent differences in
      the rate of bilateral superior posterior lobar volume change with age (P =
      0.002). Resultantly, although superior posterior lobar volume did not differ
      significantly between genotype groups at age 5 (P = 0.9), by age 23 it was 12%
      greater in Gcar than AA (P = 0.002). Our results suggest that common genetic
      variation within this putative ASD risk gene has the capacity to modify the
      development of cerebellar systems implicated in ASD neurobiology.

PMID- 22359340
TI  - High thrombin concentrations in fibrin sealants induce apoptosis in human
      keratinocytes.
AB  - Over the last century many studies have been performed to assess the impact of
      fibrin sealant (FS) components on cells. Because of the noncovalent bonding of
      thrombin to fibrin during fibrin clot formation, we wanted to further evaluate
      the impact of fibrin bound thrombin on cell viability. Initially, we quantified
      the activity of thrombin in three different, commercially available FS. This
      information was used to prepare fibrin clots covering a range of thrombin
      concentrations from 4 to 820 IU mL(-1), but which were identical with respect to
      all other constituents. Although these fibrin clots did not differ in their three
      dimensional structure, clots prepared with highly concentrated thrombin (820 IU
      mL(-1)) failed to support adhesion and spreading of primary human keratinocytes
      (NHEK). The number of attached cells was also significantly reduced on high
      thrombin activity clots. We hypothesized that these observations are not only the
      consequence of decreased proliferation but of apoptotic mechanisms, since the
      expression of cleaved caspase 3 and 7 was strongly enhanced on fibrin clots with
      high thrombin activity. This was accompanied by an induction of expression of
      Trail-R2 which is a receptor known to mediate apoptosis signals. Blocking of
      thrombin activity by hirudin led to an improvement of cell morphology and to an
      increase in number of attached cells. In addition, the induction of caspase 3 and
      7 was also reduced. Thus, here we report for the first time that fibrin bound
      thrombin does not only decrease proliferation (as already published by others),
      it also does induce NHEK apoptosis when present at high concentrations.

PMID- 22359341
TI  - Auditory stroop and absolute pitch: an fMRI study.
AB  - To date, the underlying cognitive and neural mechanisms of absolute pitch (AP)
      have remained elusive. In the present fMRI study, we investigated verbal and
      tonal perception and working memory in musicians with and without absolute pitch.
      Stimuli were sine wave tones and syllables (names of the scale tones) presented
      simultaneously. Participants listened to sequences of five stimuli, and then
      rehearsed internally either the syllables or the tones. Finally participants
      indicated whether a test stimulus had been presented during the sequence. For an
      auditory stroop task, half of the tonal sequences were congruent (frequencies of
      tones corresponded to syllables which were the names of the scale tones) and half
      were incongruent (frequencies of tones did not correspond to syllables). Results
      indicate that first, verbal and tonal perception overlap strongly in the left
      superior temporal gyrus/sulcus (STG/STS) in AP musicians only. Second, AP is
      associated with the categorical perception of tones. Third, the left STG/STS is
      activated in AP musicians only for the detection of verbal-tonal incongruencies
      in the auditory stroop task. Finally, verbal labelling of tones in AP musicians
      seems to be automatic. Overall, a unique feature of AP appears to be the
      similarity between verbal and tonal perception.

PMID- 22359343
TI  - Adenovirus-mediated RNA interference targeting FOXM1 transcription factor
      suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma.
AB  - BACKGROUND: The Forkhead Box M1 (FOXM1) transcription factor, which regulates the
      expression of genes essential for cell proliferation and transformation, is
      implicated in tumorigenesis and tumor progression. FOXM1 has attracted much
      attention as a potential target for the prevention and/or therapeutic
      intervention in human carcinomas. METHODS: The levels of FOXM1 expression in
      clinical tissue specimens and cell lines of human malignant nasopharyngeal
      carcinoma (NPC) were measured. Knockdown of FOXM1 expression was performed by
      small interfering RNA in NPC cells. An adenovirus vector (named AdFOXM1shRNA) was
      constructed to express a short hairpin RNA specific to FOXM1. The efficacy of
      AdFOXM1shRNA for tumor gene therapy in NPC cells and an in vivo NPC grafting
      model was assessed. RESULTS: A strong expression of FOXM1 was observed in
      clinical tissue specimens and cell lines of human NPC. Knockdown of FOXM1
      expression by FOXM1 specific small interfering RNA diminished the NPC cell
      proliferation. The infection of AdFOXM1shRNA in NPC cells resulted in the
      knockdown of FOXM1 mRNA and protein levels, correlated with the reduction of
      proliferation and anchorage-independent growth of the cancer cells. The growth of
      NPC tumors was significantly suppressed when inoculated mice were injected with
      AdFOXM1shRNA in the tumor. CONCLUSIONS: Together, our results suggest that FOXM1
      is a potential therapeutic target for NPC and AdFOXM1shRNA may be an additional
      gene therapeutic intervention to be evaluated in future treatment strategies for
      patients with NPC.

PMID- 22359342
TI  - Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K
      RAS-induced cellular senescence.
AB  - Expression of oncogenic K-RAS in primary cells elicits oncogene-induced cellular
      senescence (OIS), a form of growth arrest that potently opposes tumourigenesis.
      This effect has been largely attributed to transcriptional mechanisms that depend
      on the p53 tumour suppressor protein. The PML tumour suppressor was initially
      identified as a component of the PML-RARalpha oncoprotein of acute promyelocytic
      leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K-RAS
      in vivo and in vitro. We demonstrate here that oncogenic K-RAS induces PML
      protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the
      absence of p53. Under these circumstances, PML mRNA is selectively associated to
      polysomes. Importantly, we find that the PML 5' untranslated mRNA region plays a
      key role in mediating PML protein upregulation and that its presence is essential
      for an efficient OIS response. These findings demonstrate that upregulation of
      PML translation plays a central role in oncogenic K-RAS-induced OIS. Thus,
      selective translation initiation plays a critical role in tumour suppression with
      important therapeutic implications for the treatment of solid tumours and APL.

PMID- 22359344
TI  - Risk factors for onset of persistent respiratory symptoms in children with cystic
      fibrosis.
AB  - OBJECTIVES: To characterize the onset of persistent signs and symptoms of cystic
      fibrosis (CF) lung disease and identify characteristics that predict onset. STUDY
      DESIGN: Patients in the Epidemiologic Study of CF who were <4 years of age at
      enrollment and had >=2 years of follow-up were included. We defined persistence
      as a sign or symptom that was present during two consecutive encounters separated
      by 60-365 days, and persistent clubbing as >=50% of encounters with clubbing
      within 365 days. Predictors were assessed in a Cox proportional hazards model for
      age at first occurrence of each symptom. RESULTS: Each sign or symptom met the
      criterion of persistence in a substantial proportion of patients during a follow
      up period of 7 +/- 3 years (mean +/- SD; range 2-12). Risk factors that predicted
      earlier onset of signs and symptoms included pancreatic enzyme use, Pseudomonas
      aeruginosa infection, and prior diagnosis of asthma. Other risk factors had
      variable effects on signs and symptoms. CONCLUSIONS: Signs and symptoms of lung
      disease begin early in CF. Risk factors previously reported for lower forced
      expiratory volume in 1 sec are also associated with earlier onset of persistent
      signs and symptoms of CF lung disease, but their impact varies.

PMID- 22359345
TI  - CBF measurements using multidelay pseudocontinuous and velocity-selective
      arterial spin labeling in patients with long arterial transit delays: comparison
      with xenon CT CBF.
AB  - PURPOSE: To test the theory that velocity-selective arterial spin labeling
      (VSASL) is insensitive to transit delay. MATERIALS AND METHODS: Cerebral blood
      flow (CBF) was measured in ten Moyamoya disease patients using xenon computed
      tomography (xeCT) and magnetic resonance imaging (MRI), which included multiple
      pseudo-continuous ASL (pcASL) with different postlabel delays, VSASL, and dynamic
      susceptibility contrast (DSC) imaging. Correlation coefficient, root-mean-square
      difference, mean CBF error between ASL, and gold-standard xeCT CBF measurements
      as well the dependence of this error on transit delay (TD) as estimated by DSC
      time-to-peak of the residue function (Tmax) were determined. RESULTS: For pcASL
      with different postlabel delay time (PLD), CBF measurement with short PLD (1.5-2
      sec) had the strongest correlations with xeCT; VSASL had a lower but still
      significant correlation with a mean coefficient of 0.55. We noted the
      theoretically predicted dependence of CBF error on Tmax and on PLD for pcASL;
      VSASL CBF measurements had the least dependence of the error on TD. We also noted
      effects suggesting that the location of the label decay (blood vs. tissue)
      impacted the measurement, which was worse for pcASL than for VSASL. CONCLUSION:
      We conclude that VSASL is less sensitive to TD than conventional ASL techniques
      and holds promise for CBF measurements in cerebrovascular diseases with slow
      flow.

PMID- 22359346
TI  - Surgical resection for non-familial adenomatous polyposis-related intra-abdominal
      fibromatosis.
AB  - BACKGROUND: Intra-abdominal fibromatosis (IAF) in the context of familial
      adenomatosis polyposis (FAP) is associated with significant morbidity and high
      recurrence rates after surgical resection. Non-surgical treatments are therefore
      advocated. This study explored outcomes in patients with IAF not associated with
      FAP who underwent surgical resection. METHODS: Data were analysed from a
      prospectively collected database at a sarcoma tertiary referral centre. RESULTS:
      From 2001 to 2011, 15 patients without FAP underwent primary curative surgical
      resection of IAF. Their median (range) age was 42 (19-64) years. Median tumour
      size was 18 (8.5-25) cm and weight 1306 (236-2228) g. Complete macroscopic
      clearance was obtained in all patients. There were no deaths in hospital or
      within 30 days and only one patient developed a major complication. Median follow
      up was 40 (6-119) months. During follow-up two patients developed a recurrence
      after a disease-free interval of 12 and 16 months. CONCLUSION: In contrast to FAP
      associated IAF, non-FAP-associated IAF has a very low recurrence rate after
      surgical resection. Surgical resection is therefore advocated as first-line
      treatment in patients with non-FAP-associated IAF when resection can be performed
      with low morbidity.

PMID- 22359347
TI  - Regioselective cycloaddition of 3-azetidinones and 3-oxetanones with alkynes
      through nickel-catalysed carbon-carbon bond activation.
AB  - Get in the ring! The first examples of transition-metal-catalysed C-C bond
      activation of 3-azetidinones and 3-oxetanones are reported. In the presence of a
      nickel catalyst and alkynes, a regioselective and high-yielding [4+2]
      cycloaddition occurs, leading to the formation of pyridinones, pyranones and
      eventually 4,5-disubstituted 3-hydroxypyridines (see scheme).

PMID- 22359348
TI  - Use of complementary medications among older adults with cancer.
AB  - BACKGROUND: Little is known about complementary medication use among older adults
      with cancer, particularly those who are receiving chemotherapy. The objective of
      this study was to evaluate the prevalence of complementary medication use and to
      identify the factors associated with its use among older adults with cancer.
      METHODS: The prevalence of complementary medication use (defined as herbal
      agents, minerals, or other dietary supplements, excluding vitamins) was evaluated
      in a cohort of adults aged >=65 years who were about to start chemotherapy for
      their cancer. The associations between complementary medication use and patient
      characteristics (sociodemographics; comorbidities; and functional, nutritional,
      psychological, and cognitive status), medication use (number of medications and
      concurrent vitamin use), and cancer characteristics (type and stage) were
      analyzed. RESULTS: The cohort included 545 patients (mean age, 73 years; range,
      65-91 years; 52% women) with cancer (61% stage IV). Seventeen percent of these
      patients (N = 93) reported using >=1 complementary medication; the mean number of
      complementary medications among users was 2 (range, 1-10 medications).
      Complementary medication use was associated with 1) earlier cancer stage (29% had
      stage I-II disease vs 17% with stage III-IV disease; odds ratio [OR], 2.05; 95%
      confidence interval [CI], 1.21-3.49) and 2) less impairment with instrumental
      activities of daily living (OR, 1.39; 95% CI, 1.12-1.73). CONCLUSIONS:
      Complementary medication use was reported by 17% of older adults with cancer and
      was more common among those who had less advanced disease (i.e., those receiving
      adjuvant, potentially curative treatment) and higher functional status. Further
      studies are needed to determine the association between complementary medication
      use and cancer outcomes among older adults.

PMID- 22359350
TI  - Right-hemispheric processing of non-linguistic word features: implications for
      mapping language recovery after stroke.
AB  - Verbal stimuli often induce right-hemispheric activation in patients with aphasia
      after left-hemispheric stroke. This right-hemispheric activation is commonly
      attributed to functional reorganization within the language system. Yet previous
      evidence suggests that functional activation in right-hemispheric homologues of
      classic left-hemispheric language areas may partly be due to processing
      nonlinguistic perceptual features of verbal stimuli. We used functional MRI
      (fMRI) to clarify the role of the right hemisphere in the perception of
      nonlinguistic word features in healthy individuals. Participants made perceptual,
      semantic, or phonological decisions on the same set of auditorily and visually
      presented word stimuli. Perceptual decisions required judgements about stimulus
      inherent changes in font size (visual modality) or fundamental frequency contour
      (auditory modality). The semantic judgement required subjects to decide whether a
      stimulus is natural or man-made; the phonologic decision required a decision on
      whether a stimulus contains two or three syllables. Compared to phonologic or
      semantic decision, nonlinguistic perceptual decisions resulted in a stronger
      right-hemispheric activation. Specifically, the right inferior frontal gyrus
      (IFG), an area previously suggested to support language recovery after left
      hemispheric stroke, displayed modality-independent activation during perceptual
      processing of word stimuli. Our findings indicate that activation of the right
      hemisphere during language tasks may, in some instances, be driven by a
      "nonlinguistic perceptual processing" mode that focuses on nonlinguistic word
      features. This raises the possibility that stronger activation of right inferior
      frontal areas during language tasks in aphasic patients with left-hemispheric
      stroke may at least partially reflect increased attentional focus on
      nonlinguistic perceptual aspects of language.

PMID- 22359349
TI  - Reversal of experimental ethanol-induced liver steatosis by borage oil.
AB  - The aim of study was to evaluate the hepatoprotective effect of borage oil
      containing predominantly gamma-linolenic acid in rats with alcoholic
      steatohepatitis. Liver of ethanol-treated animals was characterized by fatty and
      hydropic dystrophies. Liver triglyceride contents and activitiies of serum marker
      enzymes were significantly increased. Ethanol increased nicotinamide adenine
      dinucleotide phosphate hydrogen (NADPH)-induced chemiluminescence and the
      contents of liver thiobarbituric acid reactive substances (TBARS). The reduced
      glutathione content in the liver was decreased. Ethanol enhanced liver microsomal
      cytochrome P-450 (CYP450) content, aniline p-hydroxylase and amydopyrine-N
      demethylase activities. The treatment with borage oil improved the liver
      morphology, decreased triglyceride contents and normalized serum marker enzyme
      activities. Borage oil developed an antioxidant effect in ethanol-treated rats.
      The treatment with this compound decreased NADPH-induced chemiluminescence and
      the content of lipid peroxidation products. Borage oil normalized CYP450 content
      compared with the ethanol-treated group. CYPI450 2E1 isoform is a main source of
      free oxygen radicals in the liver of ethanol-treated rats and we propose that the
      antioxidant effect of borage oil is realized via the normalization of CYP450
      content and activities of CYP450-related microsomal oxidases, as borage oil can
      improve the lipid surrounding of CYP450. In our opinion, the hepatoprotection by
      borage oil in alcoholic steatosis is connected with its antioxidant properties.

PMID- 22359351
TI  - Differential selectivity of efflux transporter inhibitors in Caco-2 and MDCK-MDR1
      monolayers: a strategy to assess the interaction of a new chemical entity with P
      gp, BCRP, and MRP2.
AB  - Determining the interaction of a molecule with membrane transporters is
      challenging because of overlapping substrate and inhibitor specificities and
      coexpression of multiple transporters. Caco-2 and MDCK-MDR1 cells were used to
      evaluate the selectivity of zosuquidar (LY335979), fumitremorgin C (FTC), and
      MK571 as inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein
      (BCRP), and multidrug resistance-associated protein 2 (MRP2), respectively.
      Although these compounds are commonly used as transporter inhibitors, the
      concentrations at which they selectively inhibit P-gp, BCRP, and MRP2 have not
      been definitively assessed. In Caco-2 cells, which express P-gp, BCRP, and MRP2,
      FTC (1 uM) selectively inhibited the efflux of BCRP substrates estrone-3-sulfate
      and genistein; however, at 10 uM, FTC partially inhibited the efflux of P-gp
      substrates paclitaxel and digoxin. MK571 (50 uM), commonly used to inhibit MRP2,
      inhibited the efflux of P-gp and BCRP probe substrates in Caco-2 cells. In MDCK
      MDR1 cells, which express human P-gp but not BCRP or MRP2, MK571 (50 uM) and FTC
      (10 uM) did not inhibit paclitaxel and digoxin efflux. Using Caco-2 cell
      monolayers, selected probe substrates, and optimized concentrations of LY335979
      (3 uM) and FTC (1 uM), we propose a strategy to evaluate the interaction of a
      molecule with P-gp, BCRP, and MRP2.

PMID- 22359352
TI  - Optimizing resource allocation for breast cancer prevention and care among Hong
      Kong Chinese women.
AB  - BACKGROUND: Recommendations about funding of interventions through the full
      spectrum of the disease often have been made in isolation. The authors of this
      report optimized budgetary allocations by comparing cost-effectiveness data for
      different preventive and management strategies throughout the disease course for
      breast cancer in Hong Kong (HK) Chinese women. METHODS: Nesting a state
      transition Markov model within a generalized cost-effectiveness analytic
      framework, costs and quality-adjusted life-years (QALYs) were compared to
      estimate average cost-effectiveness ratios for the following interventions at the
      population level: biennial mass mammography (ages 40-69 years or ages 40-79
      years), reduced waiting time for postoperative radiotherapy (by 15% or by 25%),
      adjuvant endocrine therapy (either upfront aromatase inhibitor [AI] therapy or
      sequentially with tamoxifen followed by AI) in postmenopausal women with estrogen
      receptor-positive disease, targeted immunotherapy in those with tumors that over
      express human epidermal growth factor receptor 2, and enhanced palliative
      services (either at home or as an inpatient). Usual care for eligible patients in
      the public sector was the comparator. RESULTS: In descending order, the optimal
      allocation of additional resources for breast cancer would be the following: a
      25% reduction in waiting time for postoperative radiotherapy (in US dollars:
      $5000 per QALY); enhanced, home-based palliative care ($7105 per QALY); adjuvant,
      sequential endocrine therapy ($17,963 per QALY); targeted immunotherapy ($62,092
      per QALY); and mass mammography screening of women ages 40 to 69 years ($72,576
      per QALY). CONCLUSIONS: Given the lower disease risk and different age profiles
      of patients in HK Chinese, among other newly emergent and emerging economies with
      similar transitioning epidemiologic profiles, the current findings provided
      direct evidence to support policy decisions that may be dissimilar to current
      Western practice.

PMID- 22359353
TI  - Interoceptive awareness enhances neural activity during empathy.
AB  - Empathy is a multicomponent function that includes sensorimotor, affective, and
      cognitive components. Although especially the affective component may implicate
      interoception and interoceptive awareness, the impact of interoception on empathy
      has never been evaluated behaviorally or neurophysiologically. Here, we tested
      how a preceding period of interoceptive awareness impacts and modulates neural
      activity during subsequent empathy. We used functional magnetic resonance imaging
      (fMRI) and measured the sequential interaction between interoception and empathy
      using fMRI in 18 healthy subjects. We found that the preceding interoceptive
      awareness period significantly enhanced neural activity during empathy in
      bilateral anterior insula and various cortical midline regions. The enhancement
      of neural activity during empathy in both interoceptive and empathy networks by
      preceding interoceptive awareness suggests a close relationship between
      interoception and empathy; thereby, interoception seems to be implicated to
      yielding empathy.

PMID- 22359354
TI  - Bayesian decision theoretic two-stage design in phase II clinical trials with
      survival endpoint.
AB  - In this paper, we consider two-stage designs with failure-time endpoints in
      single-arm phase II trials. We propose designs in which stopping rules are
      constructed by comparing the Bayes risk of stopping at stage I with the expected
      Bayes risk of continuing to stage II using both the observed data in stage I and
      the predicted survival data in stage II. Terminal decision rules are constructed
      by comparing the posterior expected loss of a rejection decision versus an
      acceptance decision. Simple threshold loss functions are applied to time-to-event
      data modeled either parametrically or nonparametrically, and the cost parameters
      in the loss structure are calibrated to obtain desired type I error and power. We
      ran simulation studies to evaluate design properties including types I and II
      errors, probability of early stopping, expected sample size, and expected trial
      duration and compared them with the Simon two-stage designs and a design, which
      is an extension of the Simon's designs with time-to-event endpoints. An example
      based on a recently conducted phase II sarcoma trial illustrates the method.

PMID- 22359355
TI  - Identification of a novel agarolytic gamma -Proteobacterium Microbulbifer
      maritimus and characterization of its agarase.
AB  - The phenotypic and agar degrading features of an unidentified marine bacteria was
      investigated. The strain was Gram-negative, obligatory aerobic and non motile. On
      the basis of several morphological features and a phylogenetic analysis of the
      genes coding for the 16S rDNA, this strain was identified as Microbulbifer
      maritimus. On solid agar medium, this isolate produced extracellular agarase
      which causes agar liquefaction around the colonies. An extracellular agarase was
      purified by ammonium sulfate precipitation, gel filtration and ion-exchange
      chromatography on DEAE-cellulose. The purified protein migrated as a single band
      on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it had a
      molecular mass of 75.2 kDa. The enzyme exhibited maximal activity at pH 7.5. The
      kinetic parameters of the enzyme were K(m) = 3 +/- 0.19 mM, K(cat) = 160 +/- 10
      S(-1) and K(cat) /K(m) = 53 +/- 10 S(-1) . mM(-1) .

PMID- 22359356
TI  - Design of tenofovir-UC781 combination microbicide vaginal gels.
AB  - Tenofovir (TFV) is a proven microbicide when administered topically as a vaginal
      gel. To improve its efficacy, TFV was combined with the nonnucleoside reverse
      transcriptase inhibitor UC781 in a vaginal gel. Mixture design of experiments
      theory was used to define a range of gel compositions with varying rheological
      properties and to assess in vitro drug release and tissue retention. Experiments
      and computations led to the specification of three different gels referred to as
      a spreading gel (SG), an intermediate spreading gel (ISG), and a bolus gel (BG).
      These three gels, all containing 1.0% TFV and 0.1% micronized UC781, were
      evaluated for in vitro release, in vitro tissue retention and safety, and in vivo
      pharmacokinetics in the rabbit. There were some differences in in vitro release
      rates of UC781 (the higher the gel viscosity, the slower the release rate) across
      gels, while release of TFV was independent of gel type. In an organotypic human
      vaginal-ectocervical (VEC) tissue model, the amounts of tissue-associated TFV and
      UC781 were several orders of magnitude higher than their in vitro half-maximal
      inhibitory concentration. There were no differences in VEC tissue concentrations
      of TFV or UC781 between the SG, ISG, and BG. All three gels were well tolerated
      in the VEC model as assessed by tissue viability, electrical resistance,
      histology, and cytokine (interleukin-8 and interleukin-1 beta) release. The local
      vaginal tissue concentrations in rabbits following a single dose or seven once
      daily doses were variable and generally lower than those found in the VEC tissue
      model. The approach described herein provides a rational schema to design and
      evaluate vaginal gels for use as microbicides.

PMID- 22359357
TI  - Treatment of an elderly patient with hepatocellular carcinoma: counseling from
      the patient's point of view.

PMID- 22359358
TI  - Covalent vectored binding of functional proteins by bifunctional crosslinking at
      silicone interfaces.
AB  - In the daily clinical routine, numerous synthetic medical devices are implanted
      in the human body, either temporarily or permanently. The synthetic material most
      often implanted is polydimethylsiloxane (silicone). Numerous studies have
      demonstrated that silicone is encompassed in a connective tissue capsule by the
      body, preventing integration into the surrounding tissue. This can result in
      complications. The aim of our study was to develop a simple procedure to
      functionalize the silicone surface, thereby positively affecting the material's
      biocompatibility. By combining a silanization with the use of ester activation, a
      reactive amino group is generated, which can bind any free carboxyl group.
      Directional crosslinking of a near-infrared-conjugated fluorophore antibody to
      the activated silicone surface could be demonstrated on a dose-dependent basis.
      The redox reaction at a silicone surface coated with an HRP-conjugated antibody
      caused by the addition of NBT/BCIP could be shown. Covering the silicone discs
      with an anti-FAS-antibody coating followed by a coincubation with FAS-sensitive T
      cells allowed highly significant detection of caspase-3. In summary, our
      crosslinking procedure enables the stable binding of proteins without the loss of
      biological function. Through this process, silicones could be endowed with new
      functions which could improve their biocompatibility.

PMID- 22359360
TI  - Constant and steady transgene expression of interferon-gamma by optimization of
      plasmid construct for safe and effective interferon-gamma gene therapy.
AB  - BACKGROUND: Hydrodynamic injection of pmCMV(enh) -hEF-1(prom) -muIFN-gamma, a
      plasmid DNA (pDNA) expressing murine interferon (IFN)-gamma with a murine
      cytomegalovirus (mCMV) enhancer and a human elongation factor (EF)-1 promoter,
      has been proven effective for the treatment of cancer and atopic dermatitis in
      mice. However, the initial peak of IFN-gamma soon after injection was quite high
      compared to the steady level for subsequent periods, which could cause unwanted
      adverse effects. Therefore, in the present study, aiming to optimize the
      efficacy/side-effect ratio of IFN-gamma gene transfer, we have developed plasmid
      vectors encoding murine IFN-gamma under the control of different combinations of
      promoter and enhancer sequences. METHODS: The promoter and enhancer sequence of
      pmCMV(enh) -hEF-1(prom) -huIFN-gamma, a prototype plasmid expressing human IFN
      gamma, was replaced or deleted to obtain various pDNAs. To assess the transgene
      expression profile, each pDNA was delivered to mice by hydrodynamic injection and
      the serum IFN-gamma concentration was measured periodically. On the basis of the
      results obtained, murine IFN-gamma expressing pDNAs were constructed and the body
      weight change was monitored as an indicator of adverse effects. RESULTS: The
      prototype pmCMV(enh) -hEF-1(prom) -huIFN-gamma showed a high but declining
      concentration of IFN-gamma. Those containing hROSA26 promoter expressed the
      transgene in a more constant manner with no initial high concentrations and
      scarcely reduced the body weight. CONCLUSIONS: These results indicate that
      hROSA26 promoter, irrespective of the presence and type of enhancers, is suitable
      for achieving constant and steady level of transgene expression and effective in
      avoiding the body weight loss caused by high concentrations of IFN-gamma.

PMID- 22359359
TI  - Incidence of brain metastases as a first site of recurrence among women with
      triple receptor-negative breast cancer.
AB  - BACKGROUND: This retrospective study sought to define the incidence of brain
      metastases as a first site of recurrence among women with triple receptor
      negative breast cancer (TNBC). METHODS: A total of 2448 patients with stage I
      through III TNBC who were diagnosed between 1990 and 2010 were identified. We
      computed the cumulative incidence of developing brain metastases as a first site
      of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to
      determine factors that could predict for the development of brain metastases as a
      first site of recurrence. The Kaplan-Meier product limit method was used to
      compute survival following a diagnosis of brain metastases. RESULTS: At a median
      follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a
      first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95%
      confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%),
      respectively. Among patients with stage I, II, and III disease, the 2-year
      cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P
      < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients
      with stage I, II, and III disease, respectively (P < .0001). In the multivariable
      model, patients with stage III disease had a significant increase in the risk of
      developing brain metastases as a first site of recurrence (hazards ratio = 3.51;
      95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those
      with stage II disease had a nonsignificant increased risk of developing brain
      metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92
      2.81; P = .10) compared with patients with stage I disease. Median survival
      following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months).
      CONCLUSIONS: Patients with nonmetastatic TNBC have a high early incidence of
      developing brain metastases as a first site of recurrence, which is associated
      with subsequent poor survival. Patients with stage III TNBC in particular would
      be an ideal cohort in which to research preventive strategies.

PMID- 22359362
TI  - Analytical approaches for monitoring exposure to organophosphorus and carbamate
      agents through analysis of protein adducts.
AB  - Appropriate treatment of a poisoned patient requires knowing the identity of the
      poison. This review summarizes the methods for identifying poisoning by
      organophosphorus and carbamate poisons. Mass spectrometry methods identify the
      poison from the adducts they form with proteins in blood. The most sensitive
      method uses potassium fluoride to release the organophosphorus agent from its
      covalent binding to serine 198 of human butyrylcholinesterase. The released
      poison is identified by gas chromatography-mass spectrometry. The drawback of
      this method is that it does not detect exposure to agents such as soman, because
      butyrylcholinesterase adducts with these agents age to a non-reactivatable form.
      A method that detects both aged and non-aged organophosphylated adducts as well
      as carbamate adducts is one that digests butyrylcholinesterase with a protease
      and analyzes the modified peptide by mass spectrometry. This method does not
      distinguish between poisons that have the same mass after reaction with
      butyrylcholinesterase--for example, between exposure to chlorpyrifos oxon and
      paraoxon. Albumin forms a stable, covalent bond with organophosphates on tyrosine
      411. The rate of reaction with albumin is much slower than with
      butyrylcholinesterase, but albumin adducts persist for a longer time in the
      circulation; they do not age; and they do not release the organophosphate when a
      patient is treated with an oxime.

PMID- 22359361
TI  - Augmented generalized estimating equations for improving efficiency and validity
      of estimation in cluster randomized trials by leveraging cluster-level and
      individual-level covariates.
AB  - Recent methodological advances in covariate adjustment in randomized clinical
      trials have used semiparametric theory to improve efficiency of inferences by
      incorporating baseline covariates; these methods have focused on independent
      outcomes. We modify one of these approaches, augmentation of standard estimators,
      for use within cluster randomized trials in which treatments are assigned to
      groups of individuals, thereby inducing correlation. We demonstrate the potential
      for imbalance correction and efficiency improvement through consideration of both
      cluster-level covariates and individual-level covariates. To improve small-sample
      estimation, we consider several variance adjustments. We evaluate this approach
      for continuous and binary outcomes through simulation and apply it to data from a
      cluster randomized trial of a community behavioral intervention related to HIV
      prevention in Tanzania.

PMID- 22359363
TI  - Coke formation and carbon atom economy of methanol-to-olefins reaction.
AB  - The methanol-to-olefins (MTO) process is becoming the most important non
      petrochemical route for the production of light olefins from coal or natural gas.
      Maximizing the generation of the target products, ethene and propene, and
      minimizing the production of byproducts and coke, are major considerations in the
      efficient utilization of the carbon resource of methanol. In the present work,
      the heterogeneous catalytic conversion of methanol was evaluated by performing
      simultaneous measurements of the volatile products generated in the gas phase and
      the confined coke deposition in the catalyst phase. Real-time and complete
      reaction profiles were plotted to allow the comparison of carbon atom economy of
      methanol conversion over the catalyst SAPO-34 at varied reaction temperatures.
      The difference in carbon atom economy was closely related with the coke formation
      in the SAPO-34 catalyst. The confined coke compounds were determined. A new type
      of confined organics was found, and these accounted for the quick deactivation
      and low carbon atom economy under low-reaction-temperature conditions. Based on
      the carbon atom economy evaluation and coke species determination, optimized
      operating conditions for the MTO process are suggested; these conditions
      guarantee high conversion efficiency of methanol.

PMID- 22359364
TI  - A more accurate profile of Achyrocline satureioides hypocholesterolemic activity.
AB  - The aim of this study was to investigate the effect of the aqueous extract (AE)
      of Achyrocline satureioides on serum lipid profile, liver oxidative profile and
      Na(+),K(+)-ATPase activity of rats submitted to a hyperlipidic diet. The animals
      were divided into four groups: control (C), AE 10% (A(10)), hyperlipidic (H) and
      hyperlipidic/AE 10% (HA(10)). In serum, we measured the levels of total
      cholesterol (TC), high-density lipoprotein, very-low-density lipoprotein, low
      density lipoprotein (LDL) and triglyceride (TG). In liver homogenates, we
      measured the thiobarbituric acid reactive substances, the carbonyl proteins, the
      non-protein thiols (NPSHs) and the activity of superoxide dismutase, catalase
      (CAT) and Na(+),K(+)-ATPase. We observed a significant increase in the TC and LDL
      levels in the H group. A. satureioides prevented these effects, decreased the TG
      levels in the HA(10) group and increased the NPSH levels in the A(10) and HA(10)
      groups. The H group showed an increase in the carbonyl protein level and a
      decrease in CAT and Na(+),K(+)-ATPase activities. With the use of this model,
      results show that increased levels of lipids are related to a redox imbalance in
      the liver, which is also related to the inhibition of Na(+),K(+)-ATPase activity,
      and that chronic administration of the AE of A. satureioides is capable of
      changing this profile.

PMID- 22359365
TI  - Methods for registration of magnetic resonance images of ex vivo prostate
      specimens with histology.
AB  - PURPOSE: To evaluate two methods of scanning and tissue processing to achieve
      accurate magnetic resonance (MR)-histologic correlation in human prostate
      specimens. MATERIALS AND METHODS: Two prostates had acrylic paint markers
      injected to define the plane of imaging and serve as internal fiducials. Each was
      placed on a polycarbonate plane-finder device (PFD), which was adjusted to align
      the imaging and cutting planes. Three prostates were aligned by use of a plane
      finder key (PFK), a polycarbonate plate that locks the specimen in a cylindrical
      carrier. Markers were injected for registration analysis. Prostates were imaged,
      then sectioned. Imaging software was used to create registration maps of the MR
      and histology images. Measurements between control points were made and compared.
      RESULTS: Accurate correlation was achieved between MR and histologic images. The
      mean displacement (MD) between the corresponding registration points using the
      PFD technique ranged from 1.11-1.38 mm for each section. The MD for all sections
      was 1.24 mm. The MD using the PFK technique ranged from 0.79-1.01 mm for each
      section, and the MD across all sections for the PFK was 0.92 mm. CONCLUSION: We
      describe two methods that can achieve accurate, reproducible correlation between
      MR imaging and histologic sections in human prostatectomy specimens.

PMID- 22359366
TI  - Statistical optimization of medium components for production of extracellular
      chitinase by Basidiobolus ranarum: a novel biocontrol agent against plant
      pathogenic fungi.
AB  - The influence of concentration of medium components such as colloidal chitin,
      lactose, malt extract, yeast extract, and peptone on the chitinase production
      from Basidiobolous ranarum at the flask level were studied by using statistical
      tool Central Composite Design (CCD) and analysed by Response Surface Methodology
      (RSM). The results revealed that colloidal chitin, malt extract and peptone had
      significant effect (P < 0.01) on the chitinase production at their individual
      levels. The polynomial equation of the model developed incorporates 3 linear, 3
      quadratic and 5 interactive terms. Maximum chitinase production of 3.47 U ml(-1)
      was achieved with 1.5% colloidal chitin, 0.125% lactose, 0.025% malt extract and
      0.075% peptone. After optimization, chitinase activity was increased by 7.71
      fold. A second order polynomial equation was found to be useful for the
      development of efficient bioprocess for chitinase production. To screen the
      biotechnological potential of this enzyme, degradation of fungal mycelia by
      ammonium sulphate precipitate of the same was studied for several pathogenic
      fungi-in vitro which showed promising results particularly against Rhizoctonia
      solani and Fusarium solani. This study provides the first evidence showing the
      effectiveness of RSM for the development of a robust statistical model for the
      chitinase production by Basidiobolus and for its application in the biocontrol of
      phytopathogenic fungi.

PMID- 22359367
TI  - Diffusion-weighted MRI as an adjunct to mammography in women under 50 years of
      age: an initial study.
AB  - PURPOSE: To evaluate diffusion-weighted magnetic resonance (DW) imaging as an
      adjunct to mammography for the detection of small invasive breast cancer.
      MATERIALS AND METHODS: Institutional review board standards were followed for
      this retrospective study. We performed both breast DW imaging and mammography on
      25 women under 50 years of age with pathologically proven T1 breast cancer and on
      21 healthy women under 50 years of age. Four offsite radiologists blind to the
      clinical information independently interpreted the mammograms and DW images and
      then classified their confidence level regarding the presence of breast cancer.
      The composite area under receiver operating characteristic curve (AUC), of
      mammography alone, DW imaging alone, and the combination of DW imaging and
      mammography (DWI/Cal) were calculated. RESULTS: The AUC of composite ROC curves
      of mammography, DW imaging, DWI/Cal combination, was 0.79 (95% CI, 0.72-0.87),
      0.86 (95% CI, 0.84-0.87), and 0.96 (95% CI, 0.92-1.00), respectively. CONCLUSION:
      DW imaging may be a useful adjunct to mammography in the detection of small
      invasive breast cancer in women under 50 years of age.

PMID- 22359368
TI  - Parthenolide inhibits the LPS-induced secretion of IL-6 and TNF-alpha and NF
      kappaB nuclear translocation in BV-2 microglia.
AB  - Feverfew (Tanacetum parthenium [L.] Sch. Bip. [Asteraceae]) is a popular herbal
      treatment used to prevent and treat headache and migraine. Parthenolide (PTN),
      the sesquiterpene lactonic derivative that is the plant's major component, might
      be one of the ingredients that act on mediators of inflammation. In the present
      study, in cultured lipopolysaccharide (LPS)-stimulated BV-2 microglia
      pretreatment with PTN caused a dose-dependent reduction of interleukin-6 (IL-6)
      secretion (29% by 200 nm, p < 0.001; 45% by 1 um, p < 0.001; 98% by 5 um, p <
      0.001); at 5 um, the highest concentration tested, it also reduced the secretion
      of TNF-alpha (54%, p < 0.001). Western blotting analysis on separate cytoplasmic
      and nuclear extracts showed that PTN strongly reduced the translocation of
      nuclear factor (NF)-kappaB to the cell nucleus. The reduction of microglial
      activation by inhibition of proinflammatory agents may help attenuate the onset
      and intensity of acute migraine attacks. These in vitro results provide an
      additional explanation for the efficacy of orally administered T. parthenium as
      an antimigraine agent.

PMID- 22359370
TI  - Synthesis and properties of 4,5,6-triphospha[3]radialene.
AB  - [3]Radialenes: 4,5,6-tris(2,4,6-tri-tert-butylphenyl)phospha[3]radialene has been
      synthesized. The compound can be easily handled in air under ambient conditions,
      despite the [3]radialene moiety containing P=C bonds, and exhibits red-shifted
      absorption as well as high electron-accepting ability. The unique electronic
      properties are brought about by the synergistic effect of the [3]radialene
      framework and the phosphorus substitution.

PMID- 22359369
TI  - Mood disorders in inflammatory bowel disease: relation to diagnosis, disease
      activity, perceived stress, and other factors.
AB  - BACKGROUND: Anxiety and depression are common in patients with inflammatory bowel
      disease (IBD); however, the factors associated with mood disorders in patients
      with ulcerative colitis (UC) and Crohn's disease (CD) are poorly defined.
      METHODS: In all, 103 patients with UC, 101 with CD, and 124 healthy controls
      completed the Hospital Anxiety and Depression Scale (HADS). Disease activity was
      defined both from symptom scores and in UC endoscopically, and in CD by fecal
      calprotectin and/or serum C-reactive protein. Multivariate regression analyses
      were used to identify factors associated with anxiety and depression. RESULTS: In
      both UC and CD, anxiety (HADS-A) and depression (HADS-D) scores were higher than
      in controls (HADS-A: 8.5 +/- 4.1 [mean +/- SD], 8.6 +/- 3.9, 3.2 +/- 1.8, P <
      0.001; and HADS-D: 4.1 +/- 3.3, 4.7 +/- 3.3, 1.7 +/- 1.4, P < 0.001,
      respectively). There were no differences in the prevalence of mild, moderate, and
      severe anxiety and depression in UC and CD. In UC, anxiety scores were associated
      with perceived stress and a new diagnosis of IBD; depression was associated with
      stress, inpatient status, and active disease. In CD, anxiety was associated with
      perceived stress, abdominal pain, and lower socioeconomic status, and depression
      with perceived stress and increasing age. CONCLUSIONS: Anxiety and depression are
      common in IBD. Perceived stress is associated with mood disturbances in both UC
      and CD, but the other associated factors differ in the two diseases.
      Gastroenterologists should look for mood disorders in IBD and consider stress
      management and psychotherapy in affected patients.

PMID- 22359371
TI  - Long-chain alkanes and ent-labdane-type diterpenes from Gymnosperma glutinosum
      with cytotoxic activity against the murine lymphoma L5178Y-R.
AB  - The antitumor potential of Gymnosperma glutinosum was previously reported using
      the in vitro and in vivo L5178Y-R lymphoma murine model. The present study was
      carried out to isolate and identify the cytotoxic compounds present in the
      Gymnosperma glutinosum leaf hexane extract. Gymnosperma glutinosum was collected
      in the semi-arid region of Escobedo, State of Nuevo Leon, Mexico, but it is
      commonly found in northeastern Mexico; it is traditionally used as a treatment
      for diarrhea, ulcers and rheumatism. G. glutinosum leaves were extracted with
      hexane and further fractioned and subfractioned over silica gel by gradient
      elution with hexane, chloroform, ethyl acetate and methanol. The cytotoxicity of
      fractions and subfractions was assessed in vitro against L5178Y-R lymphoma cells.
      Structure elucidation of the active compounds was determined by spectroscopic
      methods. Fractions and subfractions showed significant (p < 0.05) and
      concentration-dependent 20% to 56% cytotoxicity against L5178Y-R cells at
      concentrations ranging from 7.8 ug/mL to 500 ug/mL. The bioassay-guided
      fractionation of the hexane extract resulted in the isolation and identification
      of the alkane hentriacontane and the diterpene ent-labd-7-en-13S,14R,15-triol as
      the metabolites responsible for the activity.

PMID- 22359372
TI  - The organization of intrinsic brain activity differs between genders: a resting
      state fMRI study in a large cohort of young healthy subjects.
AB  - OBJECTIVES: To investigate, using resting state (RS) functional MRI (fMRI),
      gender-related differences of functional connectivity (FC) and functional network
      connectivity (FNC) of the human brain. EXPERIMENTAL DESIGN: One-hundred and four
      young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent
      a 10-min RS fMRI acquisition. Independent component analysis (ICA) and
      statistical parametric mapping were used to assess gender-related differences in
      RSNs, with and without correction for regional gray matter (GM) volume. The
      relationships among all RSNs was also assessed using a FNC method. PRINCIPAL
      OBSERVATIONS: For all networks, significant between-group differences of RS
      activity were found. Between-group comparisons of RSNs changed when adjusting for
      GM volume, as follows: (1) there was only marginal effect on the analysis of
      sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a
      significantly increased difference when cognitive networks (apart from one
      related to attention) were considered. Compared with women, men experienced
      increased FC in parietal and occipital regions in most RSNs, whereas women
      experienced a higher RS FC in frontal and temporal regions, and in the
      cerebellum. When compared to women, increased FNC was found in men between
      several cognitive and sensory networks, whereas women showed an increased FNC
      only between attention and right working-memory networks. CONCLUSIONS: The
      organization of intrinsic FC and FNC differ between genders. The detected
      differences could contribute to the understanding of the known between-gender
      variation in task-related recruitments, and the patterns of abnormalities
      detected in neurologic and psychiatric diseases with a gender prevalence.

PMID- 22359373
TI  - Automated tractography of the cingulate bundle in Alzheimer's disease: a
      multicenter DTI study.
AB  - PURPOSE: To evaluate the feasibility of multicenter tractography of the cingulate
      bundle (CB) in Alzheimer's disease (AD). MATERIALS AND METHODS: Automated
      deterministic tractography of the CB was applied to scans of 45 patients with
      probable AD and 58 healthy controls (HC) acquired with Siemens Sonata (1.5T; 60
      gradients), Trio (3T; 61 gradients), and Avanto (1.5T; 30 gradients). Diagnosis
      and center effects on the tracking indices fractional anisotropy (FA), mean
      diffusivity (MD), track density, and volume were estimated with analysis of
      variance. RESULTS: The multicenter coefficients of variance (CVs) in HC and AD
      patients were 7% and 7% for FA, 10% and 8% for MD, 18% and 20% for density, and
      21% and 21% for volume. Multicenter and single-center CVs were within a similar
      range. Significant center effects declined in the order MD > FA > density >
      volume. After adjustment for center and age, the AD group showed significantly
      higher MD (P < 0.001) and lower FA (P < 0.05) as compared with the HC group.
      CONCLUSION: Despite strong center effects, we detected significantly altered
      microstructural integrity of the CB in AD patients. Diffusion-tensor imaging
      indices of the CB as obtained by automated tractography might qualify as a
      biologically sustained surrogate marker for diagnostic and monitoring purposes in
      multicenter AD trials.

PMID- 22359374
TI  - Attachment models affect brain responses in areas related to emotions and empathy
      in nulliparous women.
AB  - BACKGROUND: The attachment model, as assessed by means of the Adult Attachment
      Interview (AAI), is crucial for understanding emotion regulation and feelings of
      security in human interactions as well as for the construction of the caregiving
      system. The caregiving system is a set of representations about affiliative
      behaviors, guided by sensitivity and empathy, and is fully mature in young
      adulthood. Here, we examine how different attachment models influence brain
      responses in areas related to empathy and emotions in young-adult subjects with
      secure and dismissing attachment models. METHODS: By means of AAI, we selected 11
      nulliparous young-adult females with a secure model and 12 with a dismissing
      model. Subjects underwent functional magnetic resonance, whereas imitating or
      observing and empathizing with infant facial expressions. Subjects were tested
      for alexithymia and reflective functioning. RESULTS: Dismissing subjects
      activated motor, mirror, and limbic brain areas to a significantly greater
      extent, but deactivated the medial orbitofrontal cortex (mOFC) and the perigenual
      anterior cingulated cortex (pACC). During emotional faces, increased activity in
      dismissing women was seen in the right temporal pole. Furthermore, greater
      alexithymia was correlated with greater activity in the entorhinal cortex and
      greater deactivation in the pACC/mOFC. CONCLUSIONS: These findings provide
      evidence of how the attachment model influences brain responses during a task
      eliciting attachment. In particular, hyperactivation of limbic and mirror areas
      may reflect emotional dysregulation of infantile experiences of rejection and
      lack of protection, whereas increased deactivation of fronto-medial areas may be
      the expression of the inhibition of attachment behaviors, which is a typical
      aspect of dismissing attachment.

PMID- 22359378
TI  - Anti-TNFs for prevention of postoperative recurrence of Crohn's disease: a broken
      record?

PMID- 22359379
TI  - Hydroxycinnamate conjugates as potential monolignol replacements: in vitro
      lignification and cell wall studies with rosmarinic acid.
AB  - The plasticity of lignin biosynthesis should permit the inclusion of new
      compatible phenolic monomers, such as rosmarinic acid (RA) and analogous catechol
      derivatives, into cell-wall lignins that are consequently less recalcitrant to
      biomass processing. In vitro lignin polymerization experiments revealed that RA
      readily underwent peroxidase-catalyzed copolymerization with monolignols and
      lignin oligomers to form polymers with new benzodioxane inter-unit linkages.
      Incorporation of RA permitted extensive depolymerization of synthetic lignins by
      mild alkaline hydrolysis, presumably by cleavage of ester intra-unit linkages
      within RA. Copolymerization of RA with monolignols into maize cell walls by in
      situ peroxidases significantly enhanced alkaline lignin extractability and
      promoted subsequent cell wall saccharification by fungal enzymes. Incorporating
      RA also improved cell wall saccharification by fungal enzymes and by rumen
      microflora even without alkaline pretreatments, possibly by modulating lignin
      hydrophobicity and/or limiting cell wall cross-linking. Consequently, we
      anticipate that bioengineering approaches for partial monolignol substitution
      with RA and analogous plant hydroxycinnamates would permit more efficient
      utilization of plant fiber for biofuels or livestock production.

PMID- 22359380
TI  - Is liver transplantation feasible in patients coinfected with human
      immunodeficiency virus and hepatitis C virus?

PMID- 22359381
TI  - Oxidative-mechanical stress signals stem cell niche mediated Lrp5 osteogenesis in
      eNOS(-/-)  null mice.
AB  - Calcific aortic valve disease (CAVD) is the most common indication for valve
      surgery in the USA. This study hypothesizes that CAVD develops secondary to
      Wnt3a/Lrp5 activation via oxidative-mechanical stress in eNOS null mice. eNOS(-/
      ) mice were tested with experimental diets including a control (n=20),
      cholesterol (n=20), cholesterol + Atorvastatin (n=20). After 23 weeks the mice
      were tested for the development of aortic stenosis by Echo, Histology, MicroCT,
      and RTPCR for bone markers. In vitro studies measured Wnt3a secretion from aortic
      valve endothelial cells and confirmed oxidative stress via eNOS activity. Anion
      exchange chromatography was performed to isolate the mitogenic protein.
      Myofibroblast cells were tested to induce bone formation. Cholesterol treated
      eNOS mice develop severe stenosis with an increase in Wnt3a, Lrp5, Runx2
      (threefold increase (P<0.0001) in the bicuspid versus tricuspid aortic valves.
      Secretion of Wnt3a from aortic valve endothelium in the presence of abnormal
      oxidative stress was correlated with diminished eNOS enzymatic activity and
      tissue nitrite levels. Initial characterization of the architecture for a stem
      cell nice was determined by protein isolation using anion-exchange chromatography
      and cell proliferation via thymidine incorporation. Osteoblastogenesis in the
      myofibroblast cell occurred via Lrp5 receptor upregulation in the presence of
      osteogenic media. Targeting the Wnt3a/Lrp5 pathway in valve calcification and
      activation of osteogenesis is via an oxidative-mechanical stress in CAVD. These
      findings provide a foundation for treating this disease process by targeting the
      cross talk mechanism in a resident stem cell niche.

PMID- 22359382
TI  - Normal reference ranges of inferior vena cava doppler indices from 14 to 40 weeks
      of gestation.
AB  - OBJECTIVE: To establish normal reference ranges of inferior vena cava (IVC)
      Doppler velocities in normal singleton pregnancies from 14 to 40 weeks. METHODS:
      A prospective descriptive study was conducted on normal singleton pregnancies
      with confirmed gestational age. The sonographic measurements of IVC Doppler
      indices, including preload index, peak velocity index for vein, and pulsatility
      index for vein, were determined by experienced sonographers. RESULTS: A total of
      645 measurements were performed, ranging from 12 to 30 measurements available for
      each gestational week. The relationship between gestational age and IVC Doppler
      indices was not linear. The best-fitted regression equations for the indices are
      as follows: [Formula: see text] [Formula: see text] [Formula: see text] (GA =
      gestational age in week) All IVC Doppler indices rapidly declined from 14 to 20
      weeks of gestation and then they were relatively constant or slightly decreased
      throughout the rest of pregnancy. The tables of normal reference ranges were
      constructed. CONCLUSIONS: Normal reference ranges of IVC Doppler indices for each
      gestational week from 14 to 40 weeks were constructed. This normative data may be
      a useful noninvasive tool in evaluation of fetal cardiac function.

PMID- 22359384
TI  - L1 penalized continuation ratio models for ordinal response prediction using high
      dimensional datasets.
AB  - Health status and outcomes are frequently measured on an ordinal scale. For high
      throughput genomic datasets, the common approach to analyzing ordinal response
      data has been to break the problem into one or more dichotomous response
      analyses. This dichotomous response approach does not make use of all available
      data and therefore leads to loss of power and increases the number of type I
      errors. Herein we describe an innovative frequentist approach that combines two
      statistical techniques, L(1) penalization and continuation ratio models, for
      modeling an ordinal response using gene expression microarray data. We conducted
      a simulation study to assess the performance of two computational approaches and
      two model selection criteria for fitting frequentist L(1) penalized continuation
      ratio models. Moreover, we empirically compared the approaches using three
      application datasets, each of which seeks to classify an ordinal class using
      microarray gene expression data as the predictor variables. We conclude that the
      L(1) penalized constrained continuation ratio model is a useful approach for
      modeling an ordinal response for datasets where the number of covariates (p)
      exceeds the sample size (n) and the decision of whether to use Akaike Information
      Criterion (AIC) or Bayesian Information Criterion (BIC) for selecting the final
      model should depend upon the similarities between the pathologies underlying the
      disease states to be classified.

PMID- 22359383
TI  - Cutaneous and inflammatory response to long-term percutaneous implants of sphere
      templated porous/solid poly(HEMA) and silicone in mice.
AB  - This study investigates mouse cutaneous responses to long-term percutaneously
      implanted rods surrounded by sphere-templated porous biomaterials engineered to
      mimic medical devices surrounded by a porous cuff. We hypothesized that
      keratinocytes would migrate through the pores and stop, permigrate, or
      marsupialize along the porous/solid interface. Porous/solid-core poly(2
      hydroxyethyl methacrylate) [poly(HEMA)] and silicone rods were implanted in mice
      for 14 days, and for 1, 3, and 6 months. Implants with surrounding tissue were
      analyzed (immuno)histochemically by light microscopy. Poly(HEMA)/skin implants
      yielded better morphologic data than silicone implants. Keratinocytes at the
      poly(HEMA) interface migrated in two different directions. "Ventral"
      keratinocytes contiguous with the dermal-epidermal junction migrated into the
      outermost pores, forming an integrated collar surrounding the rods. "Dorsal"
      keratinocytes appearing to emanate from the differentiated epithelial layer,
      extended upward along and into the exterior portion of the rod, forming an
      integrated sheath. Leukocytes persisted in poly(HEMA) and silicone pores for the
      duration of the study. Vascular and collagen networks within the poly(HEMA) pores
      matured as a function of time up to 3-months implantation. Nerves were not
      observed within the pores. Poly(HEMA) underwent morphological changes by 6 months
      of implantation. Marsupialization, foreign body encapsulation, and infection were
      not observed in any implants.

PMID- 22359385
TI  - Callosal fiber length and interhemispheric connectivity in adults with autism:
      brain overgrowth and underconnectivity.
AB  - Typical adults show an inverse relation between callosal fiber length and degree
      of interhemispheric connectivity. This has been hypothesized to be a consequence
      of the influence of conduction delays and cellular costs during development on
      axonal pruning, both of which increase with fiber length. Autism spectrum
      disorder (ASD) provides a test of this hypothesis: Children with ASD are known to
      have enlarged brains; thus, adults with ASD should show reductions in
      interhemispheric connectivity proportional to their degree of brain overgrowth
      during development. This prediction was tested by assessing the relation between
      both the size and structure of the corpus callosum and callosal fiber length,
      adjusting for intracranial volume, which is thought to reflect maximum brain size
      achieved during development. Using tractography to estimate the length of
      callosal fibers emanating from all areas of cortex, and through which region of
      the corpus callosum they pass, we show that adults with ASD show an inverse
      relation between callosal fiber length, adjusted for intracranial volume, and
      callosum size, and a positive relation between adjusted callosal fiber length and
      radial diffusivity. The results provide support for the hypothesized impact of
      fiber length during development.

PMID- 22359386
TI  - Photostability of antidotal oxime HI-6, impact on drug development.
AB  - HI-6 exhibits superior efficacy in the therapy of intoxication by different
      highly toxic organophosphorus nerve agents. Therefore HI-6 is a promising
      candidate for the development of new antidotes against nerve agents. For ethical
      and safety reasons antidotes containing HI-6 should get marketing authorization.
      Active pharmaceutical ingredients of medicinal products have to fulfil regulatory
      conditions in terms of purity and stability. Photostability is an essential
      parameter in this testing strategy. HI-6 was tested under conditions of ICH Q1B
      'Photostability testing of new drug substances and products'. The data showed a
      marked degradation of HI-6 after exposure to daylight. The mechanism of
      degradation could be detected as photoisomerism. The light burden dependent rate
      of photoisomerism was followed quantitatively. Based on these quantitative
      results on the amount of light induced isomeric product a pharmacological
      qualification was made. A standardized in vitro test showed a decreased ability
      of light exposed HI-6 to reactivate sarin- and paraoxon-inhibited human
      acetylcholinesterase. These results have an impact on the further development of
      antidotes containing HI-6, as light protection will probably be necessary during
      handling, packaging, storage and application.

PMID- 22359387
TI  - Glenoid bone lesions: comparison between 3D VIBE images in MR arthrography and
      nonarthrographic MSCT.
AB  - PURPOSE: To evaluate the feasibility of using a fat-suppressed 3D volumetric
      interpolated breath-hold examination (VIBE) sequence in magnetic resonance (MR)
      arthrography as a substitute for nonarthrographic multislice computed tomography
      (MSCT) in detecting glenoid bone lesions. MATERIALS AND METHODS: Fat-suppressed
      3D VIBE MR arthrography and MSCT were performed in 56 patients (46 male, 10
      female; age range, 14-51 years; mean age, 26 years). Based on the results of
      MSCT, the sensitivity and specificity of fat-suppressed 3D VIBE images for
      detection of bony Bankart lesion and glenoid bone loss were determined.
      Statistical significance of the percentages of glenoid bone loss between these
      two methods was calculated. RESULTS: Bony Bankart lesions were noted in 23
      (41.1%) of 56 glenohumeral joints, and glenoid bone loss was found in 40 (71.4%)
      of 56 patients at nonarthrographic MSCT. Compared with MSCT, the sensitivity and
      specificity of fat-suppressed 3D VIBE images in detecting bony Bankart lesions
      were 95.7%-100% and 93.9%-97.0%, respectively (kappa value = 0.926), and those in
      predicting glenoid bone loss were 95.0% and 93.8%, respectively. For
      quantification of glenoid bone loss, there was a high correlation between fat
      suppressed 3D VIBE and MSCT (r = 0.921, P < 0.001). CONCLUSION: Fat-suppressed 3D
      VIBE MR arthrography is a promising substitute for MSCT as a reliable method for
      evaluating bony Bankart lesion and glenoid bone loss.

PMID- 22359389
TI  - Spiked gold beads as substrates for single-particle SERS.
AB  - We introduce a new family of spiked particles resulting from the growth of high
      aspect ratio gold nanorods. Upon spike growth, elongated beads are obtained with
      sizes above 300 nm. Interestingly, and in contrast to smooth particles of the
      same size, these spiked-particles are not only able to sustain localized surface
      plasmon resonances and consequently enhance Raman signals, but are also big
      enough to be recognized by standard confocal optical microscopy. These spiked
      beads have been engineered into thin films to test their surface-enhanced Raman
      scattering (SERS) enhancing efficiency as a function of the particle density.
      Such films provide a high level of portability and easiness of use for "in-field"
      optical ultrasensitive analysis.

PMID- 22359388
TI  - Comfrey: a clinical overview.
AB  - Comfrey has a centuries-old tradition as a medicinal plant. Today, multiple
      randomized controlled trials have demonstrated the efficacy and safety of comfrey
      preparations for the topical treatment of pain, inflammation and swelling of
      muscles and joints in degenerative arthritis, acute myalgia in the back, sprains,
      contusions and strains after sports injuries and accidents, also in children aged
      3 or 4 and over. This paper provides information on clinical trials and non
      interventional studies published on comfrey to date and further literature,
      substantiating the fact that topical comfrey preparations are a valuable therapy
      option for the treatment of painful muscle and joint complaints.

PMID- 22359390
TI  - The first molecular level monitoring of carbohydrate conversion to 5
      hydroxymethylfurfural in ionic liquids. B2O3--an efficient dual-function metal
      free promoter for environmentally benign applications.
AB  - The mechanistic nature of the conversion of carbohydrates to the sustainable
      platform chemical 5-hydroxymethylfurfural (5-HMF) was revealed at the molecular
      level. A detailed study of the key sugar units involved in the biomass conversion
      process has shown that the simple dissolution of fructose in the ionic liquid 1
      butyl-3-methylimidazolium chloride significantly changes the anomeric composition
      and favors the formation of the open fructoketose form. A special NMR approach
      was developed for the determination of molecular structures and monitoring of
      chemical reactions directly in ionic liquids. The transformation of glucose to 5
      HMF has been followed in situ through the detection of intermediate species. A
      new environmentally benign, easily available, metal-free promoter with a dual
      functionality (B(2)O(3)) was developed for carbohydrate conversion to 5-HMF.

PMID- 22359391
TI  - Magnetization spoiling in radial FLASH contrast-enhanced MR digital subtraction
      angiography.
AB  - PURPOSE: To increase the in-plane spatial resolution and image update rates of 2D
      magnetic resonance (MR) digital subtraction angiography (DSA) pulse sequences to
      0.57 * 0.57 mm and 6 frames/sec, respectively, for intracranial vascular disease
      applications by developing a radial FLASH protocol and to characterize a new
      artifact, not previously described in the literature, which arises in the
      presence of such pulse sequences. MATERIALS AND METHODS: The pulse sequence was
      optimized and artifacts were characterized using simulation and phantom studies.
      With Institutional Review Board (IRB) approval, the pulse sequence was used to
      acquire time-resolved images from healthy human volunteers and patients with x
      ray DSA-confirmed intracranial vascular disease. RESULTS: Artifacts were shown to
      derive from inhomogeneous spoiling due to the nature of radial waveforms.
      Gradient spoiling strategies were proposed to eliminate the observed artifact by
      balancing gradient moments across TR intervals. The resulting radial 2D MR DSA
      sequence (2.6 sec temporal footprint, 6 frames/sec with sliding window factor 16,
      0.57 * 0.57 mm in-plane) demonstrated small vessel detail and corroborated x-ray
      DSA findings in intracranial vascular imaging studies. CONCLUSION: Appropriate
      gradient spoiling in radial 2D MR DSA pulse sequences improves intracranial
      vascular depiction by eliminating circular banding artifacts. The proposed pulse
      sequence may provide a useful addition to clinically applied 2D MR DSA scans.

PMID- 22359392
TI  - A novel multi-kinase inhibitor pazopanib suppresses growth of synovial sarcoma
      cells through inhibition of the PI3K-AKT pathway.
AB  - Synovial sarcoma is an aggressive soft tissue sarcoma with only a modest response
      to conventional cytotoxic agents. In the present study, we evaluated the
      potential antitumor effects of a novel anti-angiogenesis agent, pazopanib,
      against synovial sarcoma cells. We found that pazopanib directly inhibited the
      growth of synovial sarcoma cells by inducing G1 arrest. Multiplex analyses
      revealed that the PI3K-AKT pathway was highly suppressed in pazopanib-sensitive
      synovial sarcoma cells. Furthermore, administration of pazopanib highly
      suppressed the tumor growth in a xenograft model. Taken together, these results
      suggest pazopanib as a possible agent against synovial sarcoma and may warrant
      further clinical studies.

PMID- 22359393
TI  - Biocompatibility and resorption of a radiopaque premixed calcium phosphate
      cement.
AB  - Calcium phosphate cements (CPC) are used as bone void filler in various
      orthopedic indications; however, there are some major drawbacks regarding mixing,
      transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a
      premixed calcium phosphate cement (pCPC), some of these difficulties can be
      overcome. In the treatment of vertebral fractures the handling characteristics
      need to be excellent including a high radio-opacity for optimal control during
      injection. The aim of this study is to evaluate a radiopaque pCPC regarding its
      resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were
      injected into a O 4-mm drilled femur defect in rabbits. The rabbits were
      sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated
      using histology, electron microscopy, and immunohistochemical analysis. Signs of
      inflammation were evaluated both locally and systemically. The results showed a
      higher bone formation in the pCPC compared to the water-based CPC after 2 weeks
      by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in
      both groups. Both materials were considered to have a high biocompatibility since
      no marked immunological response was induced and extensive bone ingrowth was
      observed. The conclusion from the study was that pCPC with ZrO(2) radiopacifier
      is a promising alternative regarding bone replacement material and may be
      suggested for treatment of, for example, vertebral fractures based on its high
      biocompatibility, fast bone ingrowth, and good handling properties.

PMID- 22359394
TI  - A new twist on amide solvolysis.

PMID- 22359395
TI  - Detection of myo-inositol trispyrophosphate in equine urine and plasma by
      hydrophillic interaction chromatography-tandem mass spectrometry.
AB  - Myo-inositol trispyrophosphate (ITPP) is a new drug capable of increasing the
      amount of oxygen in hypoxic tissues. Studies have shown that administration of
      ITPP increases the maximal exercise capacity in normal mice as well as mice with
      severe heart failure. The properties of ITPP make it an ideal candidate as a
      doping agent to enhance performance in racehorses. While there have been
      speculations in the horseracing industry that the covert use of ITPP is already
      widespread, no reported method exists for the detection of ITPP in equine
      biological samples. ITPP is a difficult-to-detect drug due to its hydrophilic
      nature; the complexity of equine biological matrices also adds to the problem.
      This paper describes for the first time a method for the detection and
      confirmation of ITPP in equine urine and plasma. ITPP was isolated from the
      sample matrices by solid-phase extraction and the extract was analyzed by
      hydrophilic interaction chromatography-tandem mass spectrometry. ITPP could be
      detected at low ppb levels in both fortified equine plasma and urine with good
      precision, fast instrumental turnaround time, and negligible matrix
      interferences. To our knowledge, this is the first report of a validated method
      for the detection and unequivocal confirmation of low levels of ITPP in any
      biological fluid.

PMID- 22359396
TI  - Can propranolol be a viable option for the treatment of small-for-size syndrome?

PMID- 22359397
TI  - Neural substrates of the self-memory system: new insights from a meta-analysis.
AB  - The self has been the topic of philosophical inquiry for centuries.
      Neuropsychological data suggest that the declarative self can be fractionated
      into three functionally independent systems processing personal information at
      several levels of abstraction, including episodic memories of one's own life
      (episodic autobiographical memory, EAM), semantic knowledge of facts about one's
      own life (semantic autobiographical memory, SAM), and semantic summary
      representations of one's personal identity (conceptual self, CS). Our proposal
      here was to present a comprehensive description of the neural networks
      underpinning self-representations. To this aim, we performed three meta-analyses,
      one each for EAM, SAM, and CS, using the activation likelihood estimation (ALE)
      method. We expected a shift from posterior to anterior structures associated with
      the incrementally increasing level of abstraction of self-representations. The
      key finding was that EAM predominantly activates posterior and limbic regions
      including hippocampus. SAM is associated with anterior activations and also
      posterior and limbic activations in a lesser degree than EAM. CS mainly recruits
      medial prefrontal structures. Interestingly, medial prefrontal cortex is
      activated irrespective of the level of abstraction, but a more caudal part is
      recruited during CS, while SAM and EAM activate more rostral portions. To
      conclude, in line with the previous proposals, our results corroborate the idea
      that the declarative self is not monolithic but a multidimensional construct
      comprising distinct representations at different levels of abstraction.

PMID- 22359398
TI  - Seeking Huntington disease biomarkers by multimodal, cross-sectional basal
      ganglia imaging.
AB  - Neurodegeneration of the striatum in Huntington disease (HD) is characterized by
      loss of medium-spiny neurons, huntingtin nuclear inclusions, reactive gliosis,
      and iron accumulation. Neuroimaging allows in vivo detection of the macro- and
      micro-structural changes that occur from presymptomatic stages of the disease
      (preHD). The aim of our study was to evaluate the reliability of multimodal
      imaging as an in vivo biomarker of vulnerability and development of the disease
      and to characterize macro- and micro-structural changes in subcortical nuclei in
      HD. Macrostructure (T1-weighted images), microstructure (diffusion tensor
      imaging), and iron content (R 2* relaxometry) of subcortical nuclei and medial
      temporal lobe structures were evaluated by a 3 T scanner in 17 preHD carriers, 12
      early-stage patients and 29 matched controls. We observed a volume reduction and
      microstructural changes in the basal ganglia (caudate, putamen, and globus
      pallidus) and iron accumulation in the globus pallidus in both preHD and
      symptomatic subjects; all these features were significantly more pronounced in
      patients, in whom degeneration extended to the other subcortical nuclei (i.e.,
      thalamus and accumbens). Mean diffusivity (MD) was the most powerful predictor in
      models explaining more than 50% of the variability in HD development in the
      caudate, putamen, and thalamus. These findings suggest that the measurement of MD
      may further enhance the well-known predictive value of striatal volume to assess
      disease progression as it is highly sensitive to tissue microimpairment.
      Multimodal imaging may detect brain changes even in preHD stages.

PMID- 22359399
TI  - Response to biologic therapy in Crohn's disease is improved with early treatment:
      an analysis of health claims data.
AB  - BACKGROUND: Anti-tumor necrosis factor (TNF) therapy is an important treatment
      option for management of active Crohn's disease (CD) and is labeled for use after
      failure of conventional therapy (step-up). However, there is debate on the
      introduction of anti-TNF agents earlier in the treatment strategy (top-down) to
      potentially improve clinical outcomes. The aim of this study was to determine if
      a top-down approach with anti-TNF therapy is associated with improved outcomes
      for patients with active CD. METHODS: Claims data were from adult patients with
      CD with continuous enrollment in the same health plan for >= 6 months prior to
      the initial diagnostic claim for CD, >= 12 months after their initial anti-TNF
      claim, and with >= 1 anti-TNF claims after their initial diagnosis for CD.
      RESULTS: Three patient groups were identified: The Step-Up group used 5
      aminosalicylates and/or corticosteroids prior to anti-TNF; the immunosuppression
      (IS)-to-TNF inhibitor group used IS prior to anti-TNF therapy; the Early-TNF
      group initiated anti-TNF therapy within 30 days of the first prescription for CD.
      Response to anti-TNF therapy was determined up to 24 months following anti-TNF
      initiation by concomitant corticosteroid use, CD surgery, anti-TNF dose
      escalation, and anti-TNF discontinuation/switch. A top-down approach to anti-TNF
      therapy was associated with a lower risk of concomitant corticosteroid use, anti
      TNF dose escalation, discontinuation/switch of anti-TNF, and CD-related surgery
      compared with the step-up and IS-to-TNF therapy approaches. CONCLUSIONS: These
      "real-world" data show that a top-down approach to anti-TNF therapy in CD is
      associated with reductions in loss of response and fewer surgeries than
      conventional step-wise management.

PMID- 22359400
TI  - Modeling hospital length of stay by Coxian phase-type regression with
      heterogeneity.
AB  - Hospital length of stay (LOS) is an important measure of healthcare utilization
      and is generally positively skewed and heterogeneous. We fit a Coxian phase-type
      distribution to LOS and identify the hidden states of the underlying latent
      homogeneous Markov model. We demonstrate that selecting an appropriate number of
      phases and a regression model for hazard rates can account for some heterogeneity
      in LOS. Reversible jump MCMC method enables us to dynamically uncover the hidden
      stochastic Markov structure. A classification method is used to assign patients
      to different LOS groups. The methodology is illustrated with application to
      hospital admissions for acute myocardial infarction in the 2003 Nationwide
      Inpatient Sample from the Healthcare Utilization Project.

PMID- 22359401
TI  - Criteria and scheduling of quality control of B-mode and doppler ultrasonography
      equipment.
AB  - Periodic quality control (QC) for ultrasound scanners checks their overall
      performance, reducing the risk of inaccurate diagnoses. Data from routine annual
      QC activity were analyzed to optimize the scheduling and the criteria of further
      QC programs. Among all the ultrasound scanners (68 transducers) in use at the
      Regional Medical Department of the Aosta Valley, which are currently tested,
      48.6% showed problems, mainly (35.3%) related to defects detectable by physical
      and mechanical inspection. Nearly two-thirds of these problems impacted QC
      parameters. Failures were significantly related to the workload and to the
      "technological level" of the equipment. QC scheduling should therefore include a
      daily/weekly physical inspection in addition to a more complete, objective and
      software algorithms-based test, the frequency of which should be tailored on the
      basis of the equipment characteristics. (c) 2012 Wiley Periodicals, Inc. J Clin
      Ultrasound, 2012.

PMID- 22359402
TI  - Concordance and consistency of answers to the self-delivered ESPAD questionnaire
      on use of psychoactive substances.
AB  - Considering the prevalence of drug use in Italy, it is crucial to develop a
      reproducible screening test. Test-retest reliability and internal consistency are
      important indicators of a measurement's temporal stability and are a necessary
      condition for validity. The aim of the study was to assess the consistency and
      concordance of the European School Survey Project on Alcohol and Other Drugs
      (ESPAD) questionnaire; participating students completed the questionnaire twice,
      with a three-week interval. To verify the concordance for variables relating to
      use of alcohol, cigarettes and illicit drugs, the original ordinal variables as
      well as the same dichotomically recodified variables were used. Data analysis was
      done using Kappa and weighted Kappa. The method proposed by Lipsitz was used to
      evaluate the influence of gender and age on concordance. Questions about drug
      use, examined in ordinal form, show a good test-retest concordance and an
      excellent concordance for answers relating to the use of cigarettes, alcohol and
      cannabis. Regarding the effect of age adjusted for gender, 15-year-old subjects
      showed a lower concordance than 19-year-olds. ESPAD is a tool with a good
      reproducibility. Results focus on the effect of gender and age covariates on the
      concordance of answers regarding drug use and suggest the importance of examining
      the concordance in relation to the covariate levels.

PMID- 22359403
TI  - Comprehension of wh-questions precedes their production in typical development
      and autism spectrum disorders.
AB  - Children with autism spectrum disorders (ASD) rarely produce wh-questions (e.g.
      "What hit the book?") in naturalistic speech. It is unclear if this is due to
      social-pragmatic difficulties, or if grammatical deficits are also involved. If
      grammar is impaired, production of wh-questions by rote memorization might
      precede comprehension of similar forms. In a longitudinal study, 15 children with
      ASD and 18 initially language-matched typically developing (TD) toddlers were
      visited in their homes at 4-month intervals across a 3-year period. The wh
      question task was presented via intermodal preferential looking. Silent "hitting"
      events (e.g. an apple hitting a flower) were followed by test trials in which the
      apple and flower were juxtaposed on the screen. During test trials, subject-wh-
      and object-wh-question audios were sequentially presented (e.g. "What hit the
      flower?" or "What did the apple hit?"). Control audios were also presented (e.g.
      "Where's the apple/flower?"). Children's eye movements were coded off-line, frame
      by frame. To show reliable comprehension, children should look longer to the
      named item (i.e. apple or flower) during the "where" questions but less at the
      named item during the subject-wh and object-wh-questions. To compare
      comprehension to production, we coded 30-min spontaneous speech samples drawn
      from mother-child interactions at each visit. Results indicated that
      comprehension of subject- and object-wh-questions was delayed in children with
      ASD compared with age-matched TD children, but not when matched on overall
      language levels. Additionally, both groups comprehended wh-questions before
      producing similar forms, indicating that development occurred in a similar
      manner. This paper discusses the implications of our findings for language
      acquisition in ASD.

PMID- 22359404
TI  - Quality assessment of spontaneous triggered adverse event reports received by the
      Food and Drug Administration.
AB  - PURPOSE: The Food and Drug Administration (FDA) conducted a quality assessment of
      the Adverse Drug Events Spontaneous Triggered Event Reporting (ASTER) pilot
      study, which represented the FDA's first experience with the receipt of
      electronic health record (EHR)-triggered adverse event reports. The EHR-triggered
      adverse event reports from ASTER were evaluated for their utility in conducting
      FDA's pharmacovigilance work. FDA is sharing these findings to assist others who
      are pursuing the use of patient EHR data for electronic adverse event
      identification and reporting. METHODS: ASTER pilot study reports were identified
      from the FDA Adverse Event Reporting System database, then reviewed and assessed.
      RESULTS: Demographic and other objective data that can be easily derived from
      EHRs were both present in the submitted reports and relevant to the reported
      adverse drug event (ADE), but other data, such as an informative description of
      the ADE, dates that support a temporal relationship between the product and the
      event, and relevant laboratory data, were often either conflicting or lacking.
      Most of the ADEs captured in the ASTER pilot and reported to FDA are known events
      (i.e. included in product labeling) for the suspect drugs. CONCLUSION: Triggered
      adverse event reporting from patient EHRs is a potentially valuable source of
      postmarketing safety information, especially for known adverse events. Attention
      to quality is needed to ensure that the data generated from EHR-triggered ADE
      reporting systems are relevant to the reported adverse events so that the FDA and
      others engaged in pharmacovigilance can fully utilize these reports.

PMID- 22359405
TI  - Extracts from Radix Astragali and Radix Rehmanniae promote keratinocyte
      proliferation by regulating expression of growth factor receptors.
AB  - Chinese herbal medicine has long been used as a treatment for wounds. However,
      the underlying cellular and molecular mechanisms remain largely unknown. In this
      study it was shown that the proliferation of keratinocytes, which is known to
      play an important role in wound healing as the major cell type in the epidermis,
      was promoted by three herbal extracts/natural compounds: NF3 (an extract from the
      mixture of Radix Astragali (RA) and Radix Rehmanniae (RR) in the ratio of 2:1),
      stachyose (an isolated compound from Radix Rehmanniae) and extract P2-2 (a sub
      fraction from the extract of Radix Astragali). The effect of the herbal
      extracts/natural compounds on the growth of keratinocytes was not influenced by a
      high glucose level, a condition similar to diabetic patients who usually suffer
      from diabetic foot ulcers. Real time RT-PCR results showed that the expression of
      epidermal growth factor (EGF) receptor, but not transforming growth factor-beta
      (TGF-beta) receptor, was up-regulated by NF3. Moreover, treatments with the EGF
      receptor kinase inhibitor AG1478 and the MEK inhibitor U0126 resulted in the
      diminishment of the effect of the three herbal extracts/natural compounds on
      keratinocyte proliferation, indicating that EGF receptor might have a significant
      role in this action. This study has further elucidated the molecular mechanism
      under which herbal extracts/natural compounds exert their effects on the wound
      healing process.

PMID- 22359406
TI  - Expectations and violations: delineating the neural network of proactive
      inhibitory control.
AB  - The ability to stop a prepared response (reactive inhibition) appears to depend
      on the degree to which stopping is expected (proactive inhibition). Functional
      MRI studies have shown that activation during proactive and reactive inhibition
      overlaps, suggesting that the whole neural network for reactive inhibition
      becomes already activated in anticipation of stopping. However, these studies
      measured proactive inhibition as the effect of stop-signal probability on
      activation during go trials. Therefore, activation could reflect expectation of a
      stop-signal (evoked by the stop-signal probability cue), but also violation of
      this expectation because stop-signals do not occur on go trials. We addressed
      this problem, using a stop-signal task in which the stop-signal probability cue
      and the go-signal were separated in time. Hence, we could separate activation
      during the cue, reflecting expectation of the stop-signal, from activation during
      the go-signal, reflecting expectation of the stop-signal or violation of that
      expectation. During the cue, the striatum, the supplementary motor complex (SMC),
      and the midbrain activated. During the go-signal, the right inferior parietal
      cortex (IPC) and the right inferior frontal cortex (IFC) activated. These
      findings suggest that the neural network previously associated with proactive
      inhibition can be subdivided into two components. One component, including the
      striatum, the SMC, and the midbrain, activated during the cue, implicating this
      network in proactive inhibition. Another component, consisting of the right IPC
      and the right IFC, activated during the go-signal. Rather than being involved in
      proactive inhibition, this network appears to be involved in processes associated
      with violation of expectations.

PMID- 22359407
TI  - The potential of case management for people with dementia: a commentary.
AB  - BACKGROUND: A recent review of studies of case management in dementia argues that
      lack of evidence of cost-effectiveness should discourage the use of this approach
      to care. We argue that that this is too conservative a stance, given the urgent
      need throughout the world to improve the quality of care for people with dementia
      and their caregivers. We propose a research agenda on case management for people
      with dementia. METHOD: A critical comparison was made of the studies identified
      in two systematic reviews of trials of case management for dementia, with
      selective inclusion of non-trial studies and economic evaluations. RESULTS: Our
      interpretation of the literature leads us to four provisional conclusions. First,
      studies with long follow-up periods tend to show delayed relocation of people
      with dementia to care homes. Second, the quality of life of people with dementia
      and their caregivers may also influence the likelihood of relocation. Third,
      different understandings of what constitutes case management make interpretation
      of studies difficult. Fourth, we agree that the population most likely to benefit
      from case management needs to be characterised. Earlier intervention may be more
      beneficial than intervening when the condition has progressed and the
      individual's situation is highly complex. However, this runs counter to some
      definitions of case management as an administrative, professional, and systemic
      focus on people with high needs and where expensive support is accessed or in
      prospect. CONCLUSIONS: More work needs to be carried out in a more focused way in
      order to establish the value of case management for people with dementia. Since
      care home residence is such a sizeable contributor to the costs of dementia care,
      studies need to be long enough to capture possible postponed relocation. However,
      case management studies with shorter follow-up periods can still contribute to
      our understanding, since they can demonstrate improved quality of life. Future
      research should be built around a common, agreed definition of types of case
      management.

PMID- 22359408
TI  - An amine-functionalized titanium metal-organic framework photocatalyst with
      visible-light-induced activity for CO2 reduction.
AB  - Let your light shine: the photocatalytic reduction of carbon dioxide to the
      formate anion under visible light irradiation is for the first time realized over
      a photoactive Ti-containing metal-organic framework, NH(2)-MIL-125(Ti), which is
      fabricated by a facile substitution of ligands in the UV-responsive MIL-125(Ti)
      material.

PMID- 22359409
TI  - Comprehensive care for sickle cell disease immigrant patients: a reproducible
      model achieving high adherence to minimum standards of care.
AB  - BACKGROUND: Comprehensive care and advances in clinical investigations have
      reduced morbidity and mortality in sickle cell disease (SCD), but only a minority
      of children with SCD has access to comprehensive care. In Europe the majority of
      patients with SCD are immigrants who present barriers in accessing the health
      system; therefore, new evidence-based models of comprehensive care are needed to
      ensure that all SCD patients receive high-quality care, overcoming patient- and
      health system-related barriers. We wanted to verify if addressing the specific
      needs of immigrant patients contributes to improving adherence. PROCEDURES:
      Linguistic, cultural, social issues were considered in organizing comprehensive
      care in 2006. Hospital's records were used to determine access from 2006 to 2010
      and to compare adherence before and after 2006. RESULTS: Ninety-four patients
      with SCD were enrolled in comprehensive care; 94% were first generation
      immigrants (81% African). Age at diagnosis was higher for children born abroad
      vs. children born in Italy (66.08 vs 25.36 months, P < 0.005). Since 2006,
      children were seen at least once a year, with 100% adherence to follow-up
      appointments. Coverage increased from 26% to 97% for flu vaccination, from 80% to
      92% for pneumococcus immunization, from 27% to 100% for Transcranial Doppler
      (TCD) screening (P < 0.001). Emergency Department access/patient/year and
      inpatient admissions/patient/year decreased from 2.3 to 0.98 and from 0.30 to
      0.25, respectively (P < 0.001). CONCLUSIONS: Comprehensive care can be delivered
      to vulnerable groups obtaining high adherence if linguistic, cultural, social
      issues are addressed. This model may merit assessment in other communities where
      immigrants represent the majority of patients.

PMID- 22359411
TI  - Probing the effect of molecular orientation on the intensity of chemical
      enhancement using graphene-enhanced Raman spectroscopy.
AB  - A rational approach to investigate the effect of molecular orientation on the
      intensity of chemical enhancement using graphene-enhanced Raman spectroscopy
      (GERS) is developed. A planar molecule, copper phthalocyanine (CuPc), is used as
      probe molecule. Annealing allows the CuPc molecule in a Langmuir-Blodgett film to
      change orientation from upstanding to lying down. The UV-visible absorption
      spectra prove the change of the molecular orientation, as well as the variation
      of the interaction between the CuPc molecule and graphene. The Raman spectra of
      the molecule in the two different orientations are compared and analyzed. The
      results show that chemical enhancement is highly sensitive to the molecular
      orientation. The different molecular orientations induce different magnitudes of
      the interaction between the molecule and graphene. The stronger the interaction,
      the more the Raman signal is enhanced. Furthermore, the sensitivity of GERS to
      molecular orientation is promising to determine the orientation of the molecule
      on graphene. Based on this molecular orientation sensitive Raman enhancement,
      quantitative calculation of the magnitude of the chemical enhancement is
      implemented for a series of Pc derivatives. It shows that the magnitude of the
      chemical enhancement can be used to evaluate the degree of interaction between
      the molecules and graphene. Moreover, an understanding of the chemical
      enhancement in GERS is promoted and the effect of molecular orientation on the
      intensity of chemical enhancement is explained.

PMID- 22359410
TI  - Healing of intestinal inflammation by IL-22.
AB  - An interleukin (IL)-10 family cytokine, IL-22 is characterized by several unique
      biological properties, including 1) the target restricted to innate cells; 2) the
      distinct expression pattern between large and small intestines; 3) alteration of
      the cellular source depending on several factors; 4) the dual abilities to serve
      as protective versus proinflammatory mediators in inflammatory responses; and 5)
      the close association with some major inflammatory bowel disease (IBD)
      susceptibility genes. The major functions of IL-22 in the intestine are the
      stimulation of epithelial cells to produce a wide variety of antibacterial
      proteins, the reinforcement of mucus barrier through stimulation of mucin 1
      production under intestinal inflammatory conditions, and the enhancement of
      epithelial regeneration with goblet cell restitution. Through these beneficial
      functions, IL-22 contributes to the improvement of some types of experimental
      chronic colitis, which are mediated by T helper (Th)1 or Th2 responses. Most
      important, studies using both loss-of-function and gain-of-function approaches
      have clearly demonstrated the ability of IL-22 to promote intestinal wound
      healing from acute intestinal injury. These findings highlight IL-22 as an
      attractive and promising target for future IBD therapy. Alternatively, the
      enormous progress in the field of IL-22 biology has also suggested more
      complicated mechanisms with the IL-22 pathway than previously predicted. This
      review article briefly summarizes previous and current knowledge on IL-22
      particularly associated with intestinal inflammation.

PMID- 22359412
TI  - Formation of an endoplasmic reticulum ring associated with acetylated
      microtubules in the angiosperm preprophase band.
AB  - We investigated the organization of the cortical endoplasmic reticulum (ER) in
      prophase cells of the angiosperms Zea mays, Triticum turgidum, and Vigna
      sinensis. In both symmetrically and asymmetrically dividing protodermal leaf
      cells, cortical ER was enriched in the preprophase band and colocalized there
      with microtubules, forming a ring-like structure (ER ring). In contrast, ER ring
      was absent from prophase root-tip cells of the same plants, suggesting that ER
      ring formation in the preprophase band is organ specific. Immunolabeling of the
      protodermal leaf cells revealed the presence of acetylated microtubules, which
      are more stable than the nonacetylated ones. In contrast, neither this post
      translational modification of tubulin nor an accumulation of ER in the
      preprophase band was detected in root-tip cells. Experimentally delaying the
      maturation/disassembly of the microtubule ring of the preprophase band by taxol
      or cyclopiazonic acid treatment led to the appearance of ER ring and acetylated
      microtubules in the preprophase band. Together, our data show that in dividing
      cells of angiosperms, an ER ring associated with acetylated microtubules forms in
      the preprophase band.

PMID- 22359413
TI  - Sonographic appearance of nontraumatic tear of flexor carpi radialis muscle-a
      case report.
AB  - We present an unusual case of a man with a nontraumatic tear of the flexor carpi
      radialis muscle after a regular swimming exercise, without known precipitation
      factors. The muscle tear was diagnosed by ultrasonography, which showed a cystic
      mass with increased peripheral vascularity, and was confirmed by magnetic
      resonance imaging. After conservative treatment, follow-up ultrasonography showed
      resolution of the hematoma. The patient was able to continue swimming without
      pain or limitation of function.

PMID- 22359416
TI  - Preferences for the normative basis of health care priority setting: some
      evidence from two countries.
AB  - The present paper concerns the criteria people would prefer for prioritising
      health programmes. It differs from most empirical studies as subjects were not
      asked about their personal preferences for programmes per se. Rather, they were
      asked about the principles that should guide the choice of programmes. Four
      different principles were framed as arguments for alternative programmes. The
      results from population surveys in Australia and Norway suggest that people are
      least supportive of the principle that decision makers should follow the stated
      preferences of the public. Rather, respondents expressed more support for
      decisions based upon health maximisation, equality and urgency.

PMID- 22359417
TI  - Economic burden of motorcycle accidents in Northern Ghana.

PMID- 22359418
TI  - Economic burden of motorcycle accidents in Northern Ghana.
AB  - BACKGROUND: Motorcycles are the most popular means of transportation in northern
      Ghana, and their accidents are major causes of out-patient attendance and
      admissions in the Bolgatanga Municipality. OBJECTIVE: This paper estimates the
      economic burden of motorcycle accidents in the Bolgatanga Municipality in
      Northern Ghana. DESIGN: Retrospective cross-sectional cost study. METHODS: Data
      were collected from Drivers and Vehicle Licensing Authority, the Police, health
      facilities and motorcycle accident victims. Both quantitative and qualitative
      approaches were used for data collection. Cost analysis was based on the standard
      road accident cost conceptual framework. RESULTS: Ninety-eight percent of
      vehicles registered in the municipality in 2004 - 2008 were motorcycles. The
      motorcycles were significantly more than the cars registered. The economic burden
      of motorcycle accidents was estimated to be about US$1.2 million, of which, 52%
      were accident-related costs (i.e. property damage and administration) and 48%
      casualty-related costs (i.e. medical costs, out-of-pocket expenses, lost labour
      outputs, intangible costs and funeral expenses). Most motorcycle accident victims
      were in their productive ages and were males. Only a third of the motorcycles
      were insured. Majority of the riders (71%) did not possess valid driving license
      and would want to avoid the police. Main motorcycle injuries were head injuries,
      fractures, lacerations and contusions. Majority of the accidents were caused by
      lack of formal motorcycle riding training, abuse of alcohol, unrestrained animals
      and donkey carts. CONCLUSION: Motorcycle accidents could be reduced through law
      enforcement, continuous mass education and helmet use.

PMID- 22359419
TI  - Antiplasmodial activity of extracts of Tridax procumbens and Phyllanthus amarus
      in in vitro Plasmodium falciparum culture systems.
AB  - BACKGROUND: Aqueous extracts of Tridax procumbens (TP) (Compositae) and
      Phyllanthus amarus (PA) (Euphorbiaceae) are used in traditional medicine in Ghana
      to treat malaria. Previous studies have demonstrated the anti-trypanosoma, anti
      bacterial and anti-HIV effects of TP and PA. OBJECTIVE: To assess the
      antiplasmodial activity of extracts of TP and PA. METHOD: Aqueous extracts of TP
      and PA were prepared. A portion of each was freeze-dried and the remaining
      extracted sequentially with ethyl acetate and chloroform. Ethanolic extracts were
      also prepared. The antiplasmodial activity of the extracts was assessed with the
      3H-hypoxanthine assay using chloroquine-resistant (Dd2) Plasmodium falciparum
      parasites. Chloroquine was used as the reference drug. The modified tetrazolium
      based colorimetric assay was also used to evaluate the red blood cell (RBC)
      protective/antiplasmodial activities and cytotoxicities of the extracts. RESULTS:
      Results showed that TP and PA have antiplasmodial activities. The aqueous and
      ethanolic extracts of PA were the most active, yielding EC50 values of 34.9 ug/ml
      and 31.2 ug/ml, respectively in the tetrazolium-based assay. The TP and PA
      produced and IC50 values of 24.8 ug/ml and 11.7 ug/ml, respectively in the
      hypoxanthine assay. Protection of human RBCs against P. falciparum damage by the
      extracts highly correlated with their antiplasmodial activities. None of the
      extracts, within the concentration range (1.9-500 ug/ml) studied produced any
      overt toxicity to human RBCs. CONCLUSION: The results indicate that both PA and
      TP have activities against chloroquine-resistant P. falciparum (Dd2) parasites.
      The antiplasmodial principles extracted into water and ethanol but not chloroform
      or ethyl acetate.

PMID- 22359420
TI  - Analysis of lung function tests at a teaching hospital.
AB  - OBJECTIVE: To report on the proportions of restrictive, obstructive and combined
      types of respiratory diseases in patients referred to respiratory units at the
      Korle Bu Teaching Hospital. METHOD: This was a retrospective study of lung
      function test (LFT) data on patients who were referred from clinics both in and
      outside KBTH. A spirometer was used to assess various lung volume parameters.
      RESULTS: One quarter of total subjects (25.5%) had obstructive, 14.8% restrictive
      and 11.7% exhibited combined forms of respiratory disease. The rest showed none
      of the above conditions and were classified as normal. We also found differences
      in proportions of the disorders for subjects in different age and weight
      categories. Whereas obstructive respiratory disease occurred more in obese
      patients, and patients who were 35 years and above, restrictive and combined
      respiratory diseases occurred more in underweight patients, and patients below
      age 35 years. The respiratory diseases suggested in our study were found not to
      be sex-dependent. CONCLUSION: Our study indicates that obstructive lung disease
      was the most predominant respiratory lung ailment among patients referred to the
      respiratory units of Korle Bu Teaching Hospital.

PMID- 22359421
TI  - Renal status of children with sickle cell disease in Accra, Ghana.
AB  - INTRODUCTION: In West Africa, the prevalence of sickle cell disease (SCD) is 2%.
      The disease adversely affects growth, development and organ function including
      the kidneys. There is however a dearth of information about the renal status of
      SCD children in Ghana. OBJECTIVES: To assess the renal status of children with
      SCD in steady state. DESIGN: A cross-sectional case-control study. SETTING:
      Paediatric Sickle Cell Clinic, Korle Bu Teaching Hospital, Accra. PARTICIPANTS:
      Cases-357 SCD cases and 70 of their HbAA siblings as controls. METHODS:
      Documentation of their socio-demographic data, clinical data and dipstick
      urinalysis findings, and renal ultrasonography on selected participants. RESULTS:
      The mean [SD] age was 7.18 [3.15]yrs for cases and 5.16[3.28]yrs for controls.
      The genotypes were Hb SS (76.7%), Hb SC (21.8 %), and Hb Sbetathal (1.4%).
      Urinalysis showed leucocyturia in 12.6% versus 5.7% (chi2=62.5 and the p=0.000)),
      isolated proteinuria in 2.8% versus 1.43% (chi2=10.01 and p=0.001) haematuria in
      2.6% versus 0% (chi2=9.233, p=0.002) and nitrites in 2.2% versus 1.4%
      (chi2=16.3,p=0.02) of cases and controls respectively. The youngest SCD case with
      proteinuria was 2 yrs. old. Proteinuria prevalence increased with age, ,
      occurring in 5.7% of cases aged 9-11yrs. and 20.6% of cases aged 12 yrs. Two
      thirds of the proteinuria cases were aged 9-12 yrs., of whom 50% were aged 12
      yrs. Renal ultrasound findings were normal in all those examined. CONCLUSION:
      Urinary abnormalities suggesting nephropathy occur early in SCD patients in
      Ghana. Routine dipstick screening at clinic visits countrywide would help early
      detection and prompt intervention to limit renal impairment.

PMID- 22359422
TI  - The metabolic syndrome among patients with cardiovascular disease in Accra,
      Ghana.
AB  - BACKGROUND: There is evidence linking the Metabolic Syndrome with an increased
      risk of developing cardiovascular disease, previously thought to be rare in
      Africa but now a major public health concern. OBJECTIVES: To determine the
      frequency of occurrence of the Metabolic Syndrome among patients presenting with
      cardiovascular disease at the Korle Bu Teaching Hospital, Ghana. METHODS: This
      was a case-control study of 100 consecutive cardiovascular disease patients and
      100 age- and sex- matched controls who underwent an interview and physical
      examination. Anthropometric measurements and fasting blood samples for plasma
      glucose and lipids were taken. The National Cholesterol Education Programme:
      Adult Treatment Panel III criteria were used for the diagnosis of the Metabolic
      Syndrome. RESULTS: The prevalence of Metabolic Syndrome among cases and controls
      was 54% and 18% respectively, with the prevalence increasing with advancing age.
      Hypertension and central obesity were the two components with the highest
      frequency among individuals with Metabolic Syndrome. The Metabolic Syndrome was
      associated with the development of cardiovascular disease (OR=5.35, 95% CI: 2.81
      10.18, p=0.0001), with the odds ratio increasing with the number of components
      present. CONCLUSION: The Metabolic Syndrome is prevalent among cardiovascular
      disease patients attending the Korle Bu Teaching Hospital, with a significant
      association between the number of components of the Metabolic Syndrome present
      and the probability of developing a cardiovascular disease. A policy to institute
      routine screening in clinical practice and provision of appropriate interventions
      for Metabolic Syndrome components among Ghanaian adults is needed.

PMID- 22359423
TI  - The medico-legal prerequisite for initiating quarantine and isolation practices
      in public health emergency management in hospitals in Ghana.
AB  - Hospitals and other health facilities in Ghana do not appear to have standardized
      practices for quarantine and isolation in public health emergency management.
      This paper reviews the legislative framework governing the medico-legal
      prerequisites for initiating quarantine and isolation procedures as articulated
      in the Infectious Disease Act (Cap 78) 1908 amended, 1935, the Quarantine Act
      (Cap 77) 1915 amended, 1938, the Emergency Powers Act of 1994, (Act 472), and the
      National Disaster Management Act, 1996, (Act 517) in consonance with the 1992
      Constitution of Ghana. The findings provide that (1) The legislative framework
      outlines systematic standards and protocols to be followed in the committal of
      person or persons in quarantine and isolation during public health emergencies.
      (2) These standards and protocols consider as imperative, the creation of
      standardized national templates for the initiation of quarantine and isolation
      measures. (3) The non-compliance of the standards and protocols renders
      vulnerable medical facilities and hospitals with their personnel to the threat of
      medical malpractice suits and breach of professional ethics. This paper provides
      suggestions to hospital administrators and medical personnel of how to develop
      administrative templates in compliance with the law in managing public health
      emergencies. It also provides examples of such templates for possible adoption by
      hospitals and other health administrators.

PMID- 22359424
TI  - Huge abdominal mass secondary to a transverse vaginal septum and cervical
      dysgenesis.
AB  - Transverse vaginal septum is a rare occurrence. When it co-exists with cervical
      dysgenesis, it is even rarer. Primary amenorrhea with cyclic pain is one
      manifestation in post-pubertal women. A case of transverse vaginal septum with
      vaginal atresia and cervical dysgenesis is presented. Presentation as a huge
      abdominal mass and severe anaemia posed diagnostic challenges. A two-staged
      management is described as well as variation in management of the septum. The
      involvement of the patient in her follow up is also stressed.

PMID- 22359425
TI  - Retrocaval ureter: two case reports.
AB  - Retrocaval ureter also referred to as pre-ureteral vena cava is a rare congenital
      anomaly with the ureter passing posterior to the inferior vena cava. Though it is
      a congenital anomaly, patients do not normally present with symptoms until the
      3rd and 4th decades of life from a resulting hydronephrosis. We present the first
      two cases to be reported in Ghana; a 36-year-old male and a 40-year-old female
      both with right flank pains and associated right hydronephrosis. Diagnoses were
      confirmed with retrograde ureteropyelogram and both had an open surgical repair
      of the anomaly.

PMID- 22359426
TI  - Cytotoxic chalcones and antioxidants from the fruits of a Syzygium samarangense
      (Wax Jambu).
AB  - Bioassay-guided fractionation of the methanolic extracts of the pulp and seeds of
      the fruits of Syzygium samarangense Merr. & Perry (Blume) led to the
      identification of four cytotoxic compounds and eight antioxidants on the basis of
      HPLC-PDA analysis, MS, and various NMR spectroscopic techniques. Three C
      methylated chalcones, 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone (1),
      2',4'-dihydroxy-3'-methyl-6'-methoxychalcone (stercurensin, 2), and 2',4'
      dihydroxy-6'-methoxychalcone (cardamonin, 3), were isolated and displayed
      cytotoxic activity (IC(50) = 10, 35, and 35 MUM, respectively) against the SW-480
      human colon cancer cell line. Also a number of known antioxidants were obtained
      including six quercetin glycosides: reynoutrin (4), hyperin (5), myricitrin (6),
      quercitrin (7), quercetin (9), and guaijaverin (10), one flavanone: (S)
      pinocembrin (8), and two phenolic acids: gallic acid (11) and ellagic acid (12).

PMID- 22359427
TI  - In search of function for hypothetical proteins encoded by genes of SA-JA
      pathways in Oryza sativa by in silico comparison and structural modeling.
AB  - Knowledge of rice genome brings new dimensions to the management of abiotic
      stresses; however, gene sequences in the rice genome are yet to be assigned
      structure and function. Hydrogen peroxide, salicylates and jasmonates act as
      signal molecules in plants employing common machinery to manage abiotic stress.
      The present work is primarily focused to assign a structurefunction relationship
      by modeling of the hypothetical proteins of SA-JA signaling pathway known in
      Arabidopsis thaliana and compare them with corresponding proteins in rice in
      silico. Thirteen known gene sequences with their encoded proteins for SA/JA
      pathway in model plant A. thaliana were obtained and similar gene sequences from
      rice were retrieved at NCBI. Five rice gene sequences Os09g0392100, Os03g0233200,
      OsJ_33269, OsJ_23610 and Os01g0194300 resulted in hypothetical protein products
      with unknown structure and function. Modeling and comparison of 5 proteins from
      rice and Arabidopsis showed 73 - 98% identity with acceptable RMSD values of 0.6 
      1.7 upon superimposition. Results suggest conserved nature of these proteins
      during evolution. The hypothetical protein from rice contains similar functional
      protein domain as that in A. thaliana and therefore are likely to perform similar
      functions in rice. There is a cross talk between the genes in SA/JA pathway
      wherein Os09g0392100 or EDS1, Os03g0233200 or PR5, OsJ_33269 or PAD4 and
      OsJ_23610 or SFD-1 activates the pathway and Os01g0194300 or NPR1 inhibit the
      pathway. Further investigation through wet-lab experiments are in progress to
      look into suppression/activation of the genes of SAJA signaling in rice plants
      exposed to abiotic stress.

PMID- 22359428
TI  - Accommodation of profound sequence differences at the interfaces of eubacterial
      RNA polymerase multi-protein assembly.
AB  - Evolutionarily divergent proteins have been shown to change their interacting
      partners. RNA polymerase assembly is one of the rare cases which retain its
      component proteins in the course of evolution. This ubiquitous molecular
      assembly, involved in transcription, consists of four core subunits (alpha, beta,
      betaprime, and omega), which assemble to form the core enzyme. Remarkably, the
      orientation of the four subunits in the complex is conserved from prokaryotes to
      eukaryotes although their sequence similarity is low. We have studied how the
      sequence divergence of the core subunits of RNA polymerase is accommodated in the
      formation of the multi-molecular assembly, with special reference to eubacterial
      species. Analysis of domain composition and order of the core subunits in >85
      eubacterial species indicates complete conservation. However, sequence analysis
      indicates that interface residues of alpha and omega subunits are more divergent
      than those of beta, betaprime, and sigma70 subunits. Although beta and betaprime
      are generally well-conserved, residues involved in interaction with divergent
      subunits are not conserved. Insertions/deletions are also observed near
      interacting regions even in case of the most conserved subunits, beta and
      betaprime. Homology modelling of three divergent RNA polymerase complexes, from
      Helicobacter pylori, Mycoplasma pulmonis and Onion yellows phytoplasma, indicates
      that insertions/deletions can be accommodated near the interface as they
      generally occur at the periphery. Evaluation of the modeled interfaces indicates
      that they are physico-chemically similar to that of the template interfaces in
      Thermus thermophilus, indicating that nature has evolved to retain the obligate
      complex in spite of substantial substitutions and insertions/deletions.

PMID- 22359429
TI  - In vitro and In silico studies on inhibitory effects of curcumin on multi drug
      resistance associated protein (MRP1) in retinoblastoma cells.
AB  - Multi Drug Resistance (MDR) is one of the major causes of chemotherapy failure in
      human malignancies. Curcumin, the active constituent of Curcuma longa is a proven
      anticancer agent potentially modulating the expression and function of these MDR
      proteins. In this study, we attempted to test curcumin for its potential to
      inhibit the expression and function of multidrug resistance associated protein 1
      (MRP1) in retinoblastoma (RB) cell lines through western blot, RT-PCR and
      functional assays. In silico analysis were also performed to understand the
      molecular interactions conferred by curucmin on MRP1 in RB cells. Western blot
      and RTPCR analysis did not show any correlation of MRP1 expression with increase
      in concentration of curcumin. However, inhibitory effect of curcumin on MRP1
      function was observed as a decrease in the efflux of fluorescent substrate.
      Moreover, Curcumin did not affect 8-azido-ATP-biotin binding to MRP1 and it also
      showed inhibition of ATP-hydrolysis stimulated by quercetin, which is indicative
      of curcumin's interaction with the substrate binding site of MRP1. Furthermore,
      homology modelling and docking simulation studies of MRP1 also provided deeper
      insights into the molecular interactions, thereby inferring the potential binding
      mode of curcumin into the substrate binding site of MRP1.

PMID- 22359430
TI  - Clustering of PubMed abstracts using nearer terms of the domain.
AB  - Literature search is a process in which external developers provide alternative
      representations for efficient data mining of biomedical literature such as
      ranking search results, displaying summarized knowledge of semantics and
      clustering results into topics. In clustering search results, prominent
      vocabularies, such as GO (Gene Ontology), MeSH(Medical Subject Headings) and
      frequent terms extracted from retrieved PubMed abstracts have been used as topics
      for grouping. In this study, we have proposed FNeTD (Frequent Nearer Terms of the
      Domain) method for PubMed abstracts clustering. This is achieved through a two
      step process viz; i) identifying frequent words or phrases in the abstracts
      through the frequent multi-word extraction algorithm and ii) identifying nearer
      terms of the domain from the extracted frequent phrases using the nearest
      neighbors search. The efficiency of the clustering of PubMed abstracts using
      nearer terms of the domain was measured using F-score. The present study suggests
      that nearer terms of the domain can be used for clustering the search results.

PMID- 22359432
TI  - A classification scoring schema to validate protein interactors.
AB  - Hypothetical protein [HP] annotation poses a great challenge especially when the
      protein is putatively linked or mapped to another protein. With protein
      interaction networks (PIN) prevailing, many visualizers still remain unsupported
      to the HP annotation. Through this work, we propose a six-point classification
      system to validate protein interactions based on diverse features. The HP data
      set was used as a training data-set to find putative functional interaction
      partners to the remaining proteins that are waiting to be interacting. A Total
      Reliability Score (TRS) was calculated based on the six-point classification
      which was evaluated using machine learning algorithm on a single node. We found
      that multilayer perceptron of neural network yielded 81.08% of accuracy in
      modelling TRS whereas feature selection algorithms confirmed that all
      classification features are implementable. Furthermore statistical results using
      variance and co-variance analyses confirmed the usefulness of these
      classification metrics. It has been evaluated that of all the classification
      features, subcellular location (sorting signals) makes higher impact in
      predicting the function of HPs.

PMID- 22359431
TI  - Analysis of human collagen sequences.
AB  - The extracellular matrix is fast emerging as important component mediating cell
      cell interactions, along with its established role as a scaffold for cell
      support. Collagen, being the principal component of extracellular matrix, has
      been implicated in a number of pathological conditions. However, collagens are
      complex protein structures belonging to a large family consisting of 28 members
      in humans; hence, there exists a lack of in depth information about their
      structural features. Annotating and appreciating the functions of these proteins
      is possible with the help of the numerous biocomputational tools that are
      currently available. This study reports a comparative analysis and
      characterization of the alpha-1 chain of human collagen sequences. Physico
      chemical, secondary structural, functional and phylogenetic classification was
      carried out, based on which, collagens 12, 14 and 20, which belong to the FACIT
      collagen family, have been identified as potential players in diseased
      conditions, owing to certain atypical properties such as very high aliphatic
      index, low percentage of glycine and proline residues and their proximity in
      evolutionary history. These collagen molecules might be important candidates to
      be investigated further for their role in skeletal disorders.

PMID- 22359433
TI  - BiodEnz:A database of biodegrading enzymes.
AB  - Azo dyes, which re characterized by azo bonds, are a predominant class of
      colorants used in tattooing, cosmetics, foods, textile and consumer products.
      Laccases (EC 1.10.3.2), lignin peroxidases (EC 1.11.1.14) , Azo reductases (EC
      1.7.1.6) of different micro organisms are mainly useful for the development of
      biodegradation systems as they catalyse reductive cleavage of azo groups (-N=N-)
      . Laccases have very broad substrate specificity with respect to the electron
      donor and is capable of oxidizing phenols and aromatic amines. Azoreductase
      belongs to the family of oxidoreductases, acting on other nitrogenous compounds
      as donors with NAD+ or NADP+ as acceptor. Lignin peroxidase enzymes are highly
      non-specific and are well reported to decolourize various dyes We have developed
      BiodEnz database by collecting information like strains that produce particular
      enzymes, azo dyes that are degraded , substrate specificity, molecular weight,
      the optimum temperature and pH, sequence data of the above enzymes ,as the most
      effective inoculants used for bioremediation are able to degrade dyes over a
      broad concentration range, tolerate a range of environmental conditions of
      temperature, pH, and activity of the enzymes. The database can be searched by
      using a user friendly web interface. AVAILABILITY: The database is available for
      free at http://www.biodenzdatabase.in.

PMID- 22359434
TI  - The capsicum transcriptome DB: a "hot" tool for genomic research.
AB  - Chili pepper (Capsicum annuum) is an economically important crop with no
      available public genome sequence. We describe a genomic resource to facilitate
      Capsicum annuum research. A collection of Expressed Sequence Tags (ESTs) derived
      from five C. annuum organs (root, stem, leaf, flower and fruit) were sequenced
      using the Sanger method and multiple leaf transcriptomes were deeply sampled
      using with GS-pyrosequencing. A hybrid assembly of 1,324,516 raw reads yielded
      32,314 high quality contigs as validated by coverage and identity analysis with
      existing pepper sequences. Overall, 75.5% of the contigs had significant sequence
      similarity to entries in nucleic acid and protein databases; 23% of the sequences
      have not been previously reported for C. annuum and expand sequence resources for
      this species. A MySQL database and a user-friendly Web interface were constructed
      with search-tools that permit queries of the ESTs including sequence, functional
      annotation, Gene Ontology classification, metabolic pathways, and assembly
      information. The Capsicum Transcriptome DB is free available from
      http://www.bioingenios.ira.cinvestav.mx:81/Joomla/

PMID- 22359436
TI  - The protection role of heat shock protein 70 (HSP-70) in the testes of cadmium
      exposed rats.
AB  - Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate
      several proteins involved in DNA repair systems while at the same time creating
      an oxidative stress that can result in additional DNA lesions. The testis and the
      lung are the target organs for cadmium carcinogenesis. Increased production of
      oxidants in vivo can cause damage to intracellular macromolecules such as DNA,
      proteins and lipids, which in turn lead to oxidative injury. So, this
      investigation aimed to evaluate the protective role of L-Carnitine through up
      regulation of HSPs against DNA damage induced by cadmium chloride. The current
      study was carried out on forty adult male rats, each with average weight 220
      250g., were divided into 4 equal groups. 1(st) group was received saline solution
      (0.5 ml/100 g body weight) and kept as control. 2(nd) group was received 500mg /
      kg body weight L-Carnitine intraperitoneally (IP). 3(rd) group was administered
      1.2 mg cadmium chloride IP. 4(th) group was received both cadmium chloride and L
      Carnitine simultaneously. The comet assay parameters showed significantly
      increased HSP70 and DNA damage in testis cells after 10 and 56 days in the third
      group. Meanwhile, HSP70 showed significantly decreased levels after 10 days and
      56 days in the fourth group after L-Carnitine treatment simultaneously with
      cadmium chloride. The results of the present study demonstrate a damaging effect
      of cadmium chloride on DNA of the testis cells (with low stress response). This
      damaging effect increases the synthesis of HSP70 that upregulated by L-Carnitine
      treatment and showed ameliorative effect of the cells for recovery.

PMID- 22359435
TI  - Therapeutic application of natural inhibitors against snake venom phospholipase
      A(2).
AB  - Natural inhibitors occupy an important place in the potential to neutralize the
      toxic effects caused by snake venom proteins and enzymes. It has been well
      recognized for several years that animal sera, some of the plant and marine
      extracts are the most potent in neutralizing snake venom phospholipase A(2)
      (svPLA(2)). The implication of this review to update the latest research work
      which has been accomplished with svPLA(2) inhibitors from various natural sources
      like animal, marine organisms presents a compilation of research in this field
      over the past decade and revisiting the previous research report including those
      found in plants. In addition to that the bioactive compounds/inhibitor molecules
      from diverse sources like aristolochic alkaloid, flavonoids and neoflavonoids
      from plants, hydrocarbones -2, 4 dimethyl hexane, 2 methylnonane, and 2, 6
      dimethyl heptane obtained from traditional medicinal plants Tragia involucrata
      (Euphorbiaceae) member of natural products involved for the inhibitory potential
      of phospholipase A(2) (PLA(2)) enzymes in vitro and also decrease both oedema
      induced by snake venom as well as human synovial fluid PLA(2). Besides marine
      natural products that inhibit PLA(2) are manoalide and its derivatives such as
      scalaradial and related compounds, pseudopterosins and vidalols, tetracylne from
      synthetic chemicals etc. There is an overview of the role of PLA(2) in
      inflammation that provides a rationale for seeking inhibitors of PLA(2) as anti
      inflammatory agents. However, more studies should be considered to evaluate
      antivenom efficiency of sera and other agents against a variety of snake venoms
      found in various parts of the world. The implications of these new groups of
      svPLA(2) toxin inhibitors in the context of our current understanding of snake
      biology as well as in the development of new novel antivenoms therapeutics agents
      in the efficient treatment of snake envenomations are discussed.

PMID- 22359437
TI  - Analysis of expressed sequence tags (ESTs) from cocoa (Theobroma cacao L) upon
      infection with Phytophthora megakarya.
AB  - Phytophthora megakarya, the causative agent of cacao black pod disease in West
      African countries causes an extensive loss of yield. In this study we have
      analyzed 4 libraries of ESTs derived from Phytophthora megakarya infected cocoa
      leaf and pod tissues. Totally 6379 redundant sequences were retrieved from ESTtik
      database and EST processing was performed using seqclean tool. Clustering and
      assembling using CAP3 generated 3333 non-redundant (907 contigs and 2426
      singletons) sequences. The primary sequence analysis of 3333 non-redundant
      sequences showed that the GC percentage was 42.7 and the sequence length ranged
      from 101 - 2576 nucleotides. Further, functional analysis (Blast, Interproscan,
      Gene ontology and KEGG search) were executed and 1230 orthologous genes were
      annotated. Totally 272 enzymes corresponding to 114 metabolic pathways were
      identified. Functional annotation revealed that most of the sequences are related
      to molecular function, stress response and biological processes. The annotated
      enzymes are aldehyde dehydrogenase (E.C: 1.2.1.3), catalase (E.C: 1.11.1.6),
      acetyl-CoA C-acetyltransferase (E.C: 2.3.1.9), threonine ammonia-lyase (E.C:
      4.3.1.19), acetolactate synthase (E.C: 2.2.1.6), O-methyltransferase (E.C:
      2.1.1.68) which play an important role in amino acid biosynthesis and phenyl
      propanoid biosynthesis. All this information was stored in MySQL database
      management system to be used in future for reconstruction of biotic stress
      response pathway in cocoa.

PMID- 22359438
TI  - Motif mining: an assessment and perspective for amyloid fibril prediction tool.
AB  - Amyloid fibril forming regions in protein sequences are associated with a number
      of diseases. Experimental evidences compel in favor of the hypothesis that short
      motif regions are responsible for its amyloidogenic behavior. Thus, identifying
      these short peptides is critical in understanding the cause of diseases
      associated with aggregation of proteins and developing sequencetargeted anti
      aggregation drugs. Owing to the constraints of wet lab molecular techniques for
      the identification of amyloid fibril forming targets, computational methods are
      implemented to offer better and affordable in silico predictions. The present
      study takes into consideration an assessment and perspective of the recent tools
      available for predicting a peptide status: amyloidogenic or non-amyloidogenic. To
      the best of our knowledge, the existing review articles on amyloidogenic
      prediction tools have not touched upon their effectiveness in terms of true
      positive rates or false positive rates. In this work, we compare few tools such
      as Aggrescan, Amylpred and FoldAmyloid to evaluate the performance of their
      predictability based on the experimentally proved data in terms of specificity,
      sensitivity, Matthews Correlation Coefficient and Balanced accuracy. As evident
      from the results, a significant reduction of sensitivity associated with a gain
      in specificity is noted in all the tools considered under the present study.

PMID- 22359439
TI  - Identification of miRNAs in C. roseus and their potential targets.
AB  - MicroRNAs are small (20-22 nucleotides) none coding, regulatory RNAs, whose
      pivotal role in gene expression has been associated in number of diseases,
      therefore prediction of miRNA is an essential yet challenging field. In this
      study miRNAs of C. roseus are predicted along with their possible target genes. A
      total of 19,899 ESTs were downloaded from dbEST database and processed and
      trimmed through SeqClean. Nine sequences were trashed and 31 sequences were
      trimmed by the program and the resulting sequences were submitted to Repeatmasker
      and TGICL for clustering and assembly. This contig database was now used to find
      the putative miRNAs by performing a local BLAST with the miRNAs of B. rapa
      retrieved from miRBase. The targets were scanned by hybridizing screened ESTs
      with the UTRs of human using miRanda software. Finally, 7 putative miRNAs were
      found to hybridize with the various targets of signal transduction and apoptosis
      that may play significant role in preventing diseases like Leukemia, Arthritis
      and Alzheimer.

PMID- 22359440
TI  - Homology modeling, active site prediction, and targeting the anti hypertension
      activity through molecular docking on endothelin - B receptor domain.
AB  - In cardiovascular system, activation of Endothelin receptors causes
      vasoconstriction which leads to Pulmonary Arterial Hypertension (PAH). Endothelin
      receptor antagonism has emerged as an important therapeutic strategy in pulmonary
      arterial hypertension. Bosentan is intended to affect vasoconstriction,
      hypertrophic and fibrotic effects by blocking the actions of receptors ET(A) and
      ET(B). In this study we identified the action of Bosentan on endothelin B
      receptor using docking studies with homology modeled endothelin B receptor.
      Through the modeled protein, the flexible Docking study was performed with
      Bosentan and its derivatives with theoretically predicted active sites. The
      results indicated that amino acid ARG82, ARG84 and HIS197 present in endothelin B
      receptor are core important for binding activities and these residues are having
      strong hydrogen bond interactions with Bosentan. We have investigated the
      Bosentan and its derivatives interactions and scoring parameters using gold
      docking package. Among the docked compounds, one of the Bosentan derivatives
      BD(6) shows better interaction than Bosentan with endothelin B receptor. Our
      results may be helpful for further investigations in both in vivo and in vitro
      conditions.

PMID- 22359441
TI  - Design of a peptide for immunodetection of IgA antigliadin antibody for the
      purpose of screening of celiac disease.
AB  - Celiac disease (CD) is gluten induced enteropathy which requires jejunal biopsy
      for diagnosis. To select the patients for endoscopoic procedure some serologic
      tests are popular in clinical practice for screening of CD. Although gliadin is
      one of the key immuno activator of the disease; serological screening by immuno
      detection of gliadin is not recommended. In this context we have designed a
      peptide using tools of computational biology keeping molecular pathogenesis of
      the disease into consideration such that antigliadin antibody detection based
      sensitive and specific cost effective tool for screening of celiac disease can be
      developed. The designed peptide QPFPEP interacts in a stable manner with dimeric
      immunoglobin A1 molecule and its parent peptide QPFPQP are sequentially present
      in maximum number of gliadin epitopes. This hexapeptide is predicted to interact
      with dimeric IgA1, which increases in the biofluids of the CD patients.
      ABBREVIATIONS: CD - Celiac disease, TT - Tissue transglutamase, IgA -
      Immunoglobulin A, AGA - antigliadin antibody, Immunoglobulin G - IgG.

PMID- 22359442
TI  - Sequence similarity based identification of abiotic stress responsive genes in
      chickpea.
AB  - Chickpea (Cicer arietinum L.) is an important food legume crop, particularly for
      the arid regions including Indian subcontinent. Considering the detrimental
      effect of drought, temperature and salt stress on crop yield, efforts have been
      initiated in the direction of developing improved varieties and designing
      alternate strategies to sustain chickpea production in adverse environmental
      conditions. Identification of genes that confer abiotic stress tolerance in
      plants remains a challenge in contemporary plant breeding. The present study
      focused on the identification of abiotic stress responsive genes in chickpea
      based on sequence similarity approach exploiting known abiotic stress responsive
      genes from model crops or other plant species. Ten abiotic stress responsive
      genes identified in other plants were partially amplified from eight chickpea
      genotypes and their presence in chickpea was confirmed after sequencing the PCR
      products. These genes have been functionally validated and reported to play
      significant role in stress response in model plants like Arabidopsis, rice and
      other legume crops. Chickpea EST sequences available at NCBI EST database were
      used for the identification of abiotic stress responsive genes. A total of 8,536
      unique coding long sequences were used for identification of chickpea homologues
      of these abiotic stress responsive genes by sequence similarity search (BLASTN
      and BLASTX). These genes can be further explored towards achieving the goal of
      developing superior chickpea varieties providing improved yields under stress
      conditions using modern molecular breeding approaches.

PMID- 22359443
TI  - In silico identification of miRNAs and their targets from the expressed sequence
      tags of Raphanus sativus.
AB  - MicroRNAs (miRNAs) are a novel growing family of endogenous, small, non- coding,
      single-stranded RNA molecules directly involved in regulating gene expression at
      the posttranscriptional level. High conservation of miRNAs in plant provides the
      foundation for identification of new miRNAs in other plant species through
      homology alignment. Here, previous known plant miRNAs were BLASTed against the
      Expressed Sequence Tag (EST) database of Raphanus sativus, and according to a
      series of filtering criteria, a total of 48 miRNAs belonging to 9 miRNA families
      were identified, and 16 potential target genes of them were subsequently
      predicted, most of which seemed to encode transcription factors or enzymes
      participating in regulation of development, growth and other physiological
      processes. Overall, our findings lay the foundation for further researches of
      miRNAs function in R.sativus.

PMID- 22359444
TI  - Ectomychorrizal DB: a symbiotic association database.
AB  - Ectomycorrhizal (ECM) fungal species, a "Symbiotic" relationship between tress
      and fungi in forest has a great ecological and economic importance. Here is an
      attempt to describe database named "EctomycorrhizalDB", addressing ECM diversity
      of Central Himalaya (Kumaun region), with special emphasis on their
      characterization, physical properties and morphological features along with
      specifications. This database would help the scientific community to draw a
      better understanding of the environmental factors that affects species diversity.
      AVAILABILITY: The database is available for free at
      http://www.kubic.nic.in/ectomychorhiza.

PMID- 22359445
TI  - Geno viewer, a SAM/BAM viewer tool.
AB  - The ever evolving Next Generation Sequencing technology is calling for new and
      innovative ways of data processing and visualization. Following a detailed survey
      of the current needs of researchers and service providers, the authors have
      developed GenoViewer: a highly user-friendly, easy-to-operate SAM/BAM viewer and
      aligner tool. GenoViewer enables fast and efficient NGS assembly browsing,
      analysis and read mapping. It is highly customized, making it suitable for a wide
      range of NGS related tasks. Due to its relatively simple architecture, it is easy
      to add specialised visualization functionalities, facilitating further customised
      data analysis. The software's source code is freely available; it is open for
      project and task-specific modifications. AVAILABILITY: The database is available
      for free at http://www.genoviewer.com/

PMID- 22359446
TI  - A structure-similarity-based software for the cardiovascular toxicity prediction
      of traditional chinese medicine.
AB  - Although natural medicines are generally considered to be safer than synthetic
      medicines, some reports on toxicity of many herb drugs, for example Traditional
      Chinese Medicine (TCM), attract more and more common public attention recently.
      The reasons for these cardiovascular toxic effects are not always satisfactory.
      Not all these clinical symptoms can be observed regularly. Cardiovascular
      toxicity concern is one of the hindrances for TCM to enter international markets.
      Therefore, we create web-based software for people to evaluate TCM cardiovascular
      toxicity. The software, TCM Cardiovascular Toxicity Prediction (TCMCardioTox), is
      based on structure similarity search algorithm
      (http://rcdd.sysu.edu.cn:8080/home.aspx). When a user enter a TCM name, the
      system interprets the name as a number of active component structures, and
      computes the structure similarities of the components against a number of known
      toxiphores. If one of the similarity is greater than a given similarity
      threshold, the TCM will be reported as an alert TCM for medical uses.

PMID- 22359447
TI  - Correlation between radioactivity and chemotherapeutics of the (111)In-VNB
      liposome in pharmacokinetics and biodistribution in rats.
AB  - BACKGROUND: The combination of a radioisotope with a chemotherapeutic agent in a
      liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal
      vinorelbine, [(111)In-VNB-liposome]) has been reported to show better therapeutic
      efficiency in tumor growth suppression. Nevertheless, the challenge remains as to
      whether this therapeutic effect is attributable to the combination of a
      radioisotope with chemotherapeutics. The goal of this study was to investigate
      the pharmacokinetics, biodistribution, and correlation of Indium-111
      radioactivity and vinorelbine concentration in the (111)In-VNB-liposome. METHODS:
      The VNB-liposome and (111)In-VNB-liposome were administered to rats. Blood,
      liver, and spleen tissue were collected to determine the distribution profile of
      the (111)In-VNB-liposome. A liquid chromatography tandem mass spectrometry system
      and gamma counter were used to analyze the concentration of vinorelbine and
      radioactivity of Indium-111. RESULTS: High uptake of the (111)In-VNB-liposome in
      the liver and spleen demonstrated the properties of a nanosized drug delivery
      system. Linear regression showed a good correlation (r = 0.97) between Indium-111
      radioactivity and vinorelbine concentration in the plasma of rats administered
      the (111)In-VNB-liposome. CONCLUSION: A significant positive correlation between
      the pharmacokinetics and biodistribution of (111)Indium radioactivity and
      vinorelbine in blood, spleen, and liver was found following administration of the
      (111)In-VNB-liposome. The liposome efficiently encapsulated both vinorelbine and
      Indium-111, and showed a similar concentration-radioactivity time profile,
      indicating the correlation between chemotherapy and radiotherapy could be
      identical in the liposomal formulation.

PMID- 22359448
TI  - Biscarbamate cross-linked polyethylenimine derivative with low molecular weight,
      low cytotoxicity, and high efficiency for gene delivery.
AB  - Polyethylenimine (PEI), especially PEI 25 kDa, has been widely studied for
      delivery of nucleic acid drugs both in vitro and in vivo. However, it lacks
      degradable linkages and is too toxic for therapeutic applications. Hence, low
      molecular-weight PEI has been explored as an alternative to PEI 25 kDa. To reduce
      cytotoxicity and increase transfection efficiency, we designed and synthesized a
      novel small-molecular-weight PEI derivative (PEI-Et, Mn: 1220, Mw: 2895) with
      ethylene biscarbamate linkages. PEI-Et carried the ability to condense plasmid
      DNA (pDNA) into nanoparticles. Gel retardation assay showed complete condensation
      of pDNA at w/w ratios that exceeded three. The particle size of polymer/pDNA
      complexes was between 130 nm and 180 nm and zeta potential was 5-10 mV, which
      were appropriate for cell endocytosis. The morphology of PEI-Et/pDNA complexes
      observed by atomic force microscopy (AFM) was spherically shaped with diameters
      of 110-190 nm. The transfection efficiency of polymer/pDNA complexes as
      determined with the luciferase activity assay as well as fluorescence-activated
      cell-sorting analysis (FACS) was higher than commercially available PEI 25 kDa
      and Lipofectamine 2000 in various cell lines. Also, the polymer exhibited
      significantly lower cytotoxicity compared to PEI 25 kDa at the same concentration
      in three cell lines. Therefore, our results indicated that the PEI-Et would be a
      promising candidate for safe and efficient gene delivery in gene therapy.

PMID- 22359449
TI  - Self-microemulsifying drug-delivery system for improved oral bioavailability of
      probucol: preparation and evaluation.
AB  - The objective of our investigation was to design a self-microemulsifying drug
      delivery system (SMEDDS) to improve the bioavailability of probucol. SMEDDS was
      composed of probucol, olive oil, Lauroglycol FCC, Cremophor EL, Tween-80, and PEG
      400. Droplet sizes were determined. In vitro release was investigated.
      Pharmacokinetics and bioavailability of probucol suspension, oil solution, and
      SMEDDS were evaluated and compared in rats. Plasma drug concentration was
      determined by high-performance liquid chromatography. After administration of
      probucol suspension, plasma drug concentration was very low. Relative
      bioavailability of SMEDDS was dramatically enhanced in an average of 2.15- and
      10.22-fold that of oil solution and suspension, respectively. It was concluded
      that bioavailability of probucol was enhanced greatly by SMEDDS. Improved
      solubility and lymphatic transport may contribute to the enhancement of
      bioavailability.

PMID- 22359451
TI  - Evaluation of the increase in permeability of the blood-brain barrier during
      tumor progression after pulsed focused ultrasound.
AB  - PURPOSE: The purpose of this study was to evaluate the permeability of the blood
      brain barrier after sonication by pulsed high-intensity focused ultrasound and to
      determine if such an approach increases the tumor:ipsilateral brain permeability
      ratio. MATERIALS AND METHODS: F98 glioma-bearing Fischer 344 rats were injected
      intravenously with Evans blue with or without blood-tumor barrier disruption
      induced by transcranial pulsed high-intensity focused ultrasound. Sonication was
      applied at a frequency of 1 MHz with a 5% duty cycle and a repetition frequency
      of 1 Hz. The permeability of the blood-brain barrier was assessed by the
      extravasation of Evans blue. Contrast-enhanced magnetic resonance images were
      used to monitor the gadolinium deposition path associated with transcranial
      pulsed high-intensity focused ultrasound, and the influencing size and location
      was also investigated. In addition, whole brain histological analysis was
      performed. The results were compared by two-tailed unpaired t-test. RESULTS: The
      accumulation of Evans blue in brains and the tumor:ipsilateral brain permeability
      ratio of Evans blue were significantly increased after pulsed high-intensity
      focused ultrasound exposure. Evans blue injection followed by sonication showed
      an increase in the tumor:ipsilateral brain ratio of the target tumors (9.14:1) of
      about 2.23-fold compared with the control tumors (x4.09) on day 6 after tumor
      implantation. Magnetic resonance images showed that pulsed high-intensity focused
      ultrasound locally enhances the permeability of the blood-tumor barrier in the
      glioma-bearing rats. CONCLUSION: This method could allow enhanced synergistic
      effects with respect to other brain tumor treatment regimens.

PMID- 22359450
TI  - Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and
      multidrug-resistant cancer.
AB  - BACKGROUND: Delivery of a high concentration of anticancer drugs specifically to
      cancer cells remains the biggest challenge for the treatment of multidrug
      resistant cancer. Poloxamers and D-alpha-Tocopheryl polyethylene glycol 1000
      succinate (TPGS) are known inhibitors of P-glycoprotein (P-gp). Mixed micelles
      prepared from Poloxamer 407 and TPGS may increase the therapeutic efficacy of the
      drug by delivering high concentrations inside the cells and inhibiting P-gp.
      Gambogic acid (GA) is a naturally derived novel anticancer agent, but poor
      solubility and toxic side effects limit its use. In this study, we have developed
      Poloxamer 407 and TPGS mixed micelle-encapsulating GA for the treatment of breast
      and multidrug-resistant cancer. METHODS: GA-loaded Poloxamer 407/TPGS mixed
      micelles were prepared using a thin film hydration method, and their
      physicochemical properties were characterized. Cellular accumulation and
      cytotoxicity of the GA-loaded Poloxamer 407/TPGS mixed micelles were studied in
      breast cancer cells, MCF-7 cells, and multidrug-resistant NCI/ADR-RES cells.
      RESULTS: The diameter of GA-loaded Poloxamer 407/TPGS mixed micelles was about
      17.4 +/- 0.5 nm and the zeta potential -13.57 mV. The entrapment efficiency of GA
      was 93.1% +/- 0.5% and drug loading was about 9.38% +/- 0.29%. Differential
      scanning calorimetry and X-ray powder diffraction studies confirmed that GA is
      encapsulated by the polymers. The in vitro release studies showed that mixed
      micelles sustained the release of GA for more than 4 days. Results from cellular
      uptake studies indicated that GA-loaded Poloxamer 407/TPGS mixed micelles had
      increased cellular uptake of GA in NCI/ADR-RES cells. Cytotoxicity of GA-loaded
      Poloxamer 407/TPGS mixed micelles was found to be 2.9 times higher in multidrug
      resistant NCI/ADR-RES cells, and 1.6 times higher in MCF-7 cells, as compared
      with unencapsulated GA. CONCLUSION: This study suggests that Poloxamer 407/TPGS
      mixed micelles can be used as a delivery system for GA to treat breast and
      multidrug-resistant cancer.

PMID- 22359452
TI  - Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug
      encapsulation.
AB  - BACKGROUND: Development of anticancer drugs is challenging. Indeed, much research
      effort has been spent in the development of new drugs to improve clinical
      outcomes with minimal toxicity. We have previously reported that a formulation of
      lipid gold porphyrin nanoparticles reduced systemic drug toxicity when compared
      with free gold porphyrin. In this study, we investigated the delivery and
      treatment efficiency of PEG surface-modified lipid nanoparticles as a carrier
      platform. METHODS: We encapsulated antitumor drugs into PEG-modified lipid
      nanoparticles and these were characterized by size, zeta potential, and
      encapsulation efficiency. The delivery efficiency into tumor tissue was evaluated
      using a biodistribution study. To evaluate antitumor efficacy, gold porphyrin or
      camptothecin (a DNA topoisomerase I inhibitor) were encapsulated and compared
      using an in vivo neuroblastoma (N2A) model. RESULTS: We showed that drug
      encapsulation into PEG-modified lipid nanoparticles enhanced the preferential
      uptake in tumor tissue. Furthermore, higher tumor killing efficiency was observed
      in response to treatment with PEG-modified lipid nanoparticles encapsulating gold
      porphyrin or camptothecin when compared with free gold porphyrin or free
      camptothecin. The in vivo antitumor effect was further confirmed by study of
      tumor inhibition and positive apoptosis activity. Surface modification of
      lipophilic nanoparticles with PEG increased the efficiency of drug delivery into
      tumor tissue and subsequently more effective antitumor activity. CONCLUSION: This
      specific design of a chemotherapeutic agent using nanotechnology is important in
      the development of a safe and effective drug in cancer therapy.

PMID- 22359453
TI  - Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in
      the localized treatment of intraperitoneally grown human ovarian tumor xenograft.
AB  - Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising
      results clinically; however, high locoregional concentration of the drug could
      lead to adverse side effects. In this study, IP administration was coupled with a
      folate receptor-targeted (FRT) liposomal system, in an attempt to achieve
      intracellular delivery of the Pt-based drug carboplatin in order to increase
      therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of
      FRT carboplatin liposomes was compared with the activity of free drug and
      nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian
      cancer cells as the model. Significant reduction in cell viability was observed
      with FRT liposomes, which, compared with the free drug, provided an approximately
      twofold increase in carboplatin potency. The increase in drug potency was
      correlated with significantly higher cellular accumulation of Pt resulting from
      FRT liposomal delivery. Further evaluation was conducted in mice bearing
      intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior
      survival rate (five out of six animals) was achieved in animals treated with FRT
      carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and
      following a schedule of twice-weekly administration for 3 weeks. In contrast, no
      survivors were observed in the free drug or NT carboplatin liposome groups. The
      presence of cancer cells in lung and liver tissues was observed in the saline,
      free carboplatin, and NT carboplatin liposome groups. However, there was no sign
      of cancer cells or drug-related toxicity detected in tissues from the animals
      treated with FRT carboplatin liposomes. The results of this study have
      demonstrated for the first time that the approach of coupling IP administration
      with FRT liposomal delivery could provide significantly improved therapeutic
      efficacy of carboplatin in the treatment of metastatic ovarian cancer.

PMID- 22359454
TI  - Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for
      repair of infected wounds: an in vitro and in vivo study.
AB  - BACKGROUND: The purpose of this study was to develop novel sandwich-structured
      nanofibrous membranes to provide sustained-release delivery of vancomycin,
      gentamicin, and lidocaine for repair of infected wounds. METHODS: To prepare the
      biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and
      various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were
      first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into
      sandwich-structured membranes with PLGA/collagen as the surface layers and
      PLGA/drugs as the core. An elution method and a high-pressure liquid
      chromatography assay were used to characterize in vivo and in vitro drug release
      from the membranes. In addition, repair of infected wounds in rats was studied.
      Histological examination of epithelialization and granulation at the wound site
      was also performed. RESULTS: The biodegradable nanofibrous membranes released
      large amounts of vancomycin and gentamicin (well above the minimum inhibition
      concentration) and lidocaine in vivo for more than 3 weeks. A bacterial
      inhibition test was carried out to determine the relative activity of the
      antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous
      membranes were functionally active in treating infected wounds, and were very
      effective as accelerators in early-stage wound healing. CONCLUSION: Using the
      electrospinning technique, we will be able to manufacture biodegradable,
      biomimetic, nanofibrous, extracellular membranes for long-term delivery of
      various drugs.

PMID- 22359455
TI  - Generation of THz frequency using PANDA ring resonator for THz imaging.
AB  - In this study, we have generated terahertz (THz) frequency by a novel design of
      microring resonators for medical applications. The dense wavelength-division
      multiplexing can be generated and obtained by using a Gaussian pulse propagating
      within a modified PANDA ring resonator and an add/drop filter system. Our results
      show that the THz frequency region can be obtained between 40-50 THz. This area
      of frequency provides a reliable frequency band for THz pulsed imaging.

PMID- 22359456
TI  - Effect of magnetic nanoparticles on apoptosis and cell cycle induced by wogonin
      in Raji cells.
AB  - Traditional Chinese medicine is gradually becoming a new source of anticancer
      drugs. One such example is wogonin, which is cytotoxic to various cancer cell
      lines in vitro. However, due to its low water solubility, wogonin is restricted
      to clinical administration. Recently, the application of drug-coated magnetic
      nanoparticles (MNPs) to increase water solubility of the drug and to enhance its
      chemotherapeutic efficiency has attracted much attention. In this study, wogonin
      was conjugated with the drug delivery system of MNPs by mechanical absorption
      polymerization to fabricate wogonin-loaded MNPs. It was demonstrated that MNPs
      could strengthen wogonin-induced cell inhibition, apoptosis, and cell cycle
      arrest in Raji cells by methylthiazol tetrazolium assay, flow cytometer assay,
      and nuclear 4',6-diamidino-2-phenylindole staining. Furthermore, the molecular
      mechanisms of these phenomena were explored by western blot, in which the protein
      levels of caspase 8 and caspase 3 were increased significantly while those of
      survivin and cyclin E were decreased significantly in wogonin-MNPs group. These
      findings suggest that the combination of wogonin and MNPs provides a promising
      strategy for lymphoma therapy.

PMID- 22359457
TI  - Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by
      macrophages.
AB  - The assessment of macrophage response to nanoparticles is a central component in
      the evaluation of new nanoparticle designs for future in vivo application. This
      work investigates which feature, nanoparticle size or charge, is more predictive
      of non-specific uptake of nanoparticles by macrophages. This was investigated by
      synthesizing a library of polymer-coated iron oxide micelles, spanning a range of
      30-100 nm in diameter and -23 mV to +9 mV, and measuring internalization into
      macrophages in vitro. Nanoparticle size and charge both contributed towards non
      specific uptake, but within the ranges investigated, size appears to be a more
      dominant predictor of uptake. Based on these results, a protease-responsive
      nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)
      cleavable polymeric corona. These nanoparticles are able to respond to MMP-9
      activity through the shedding of 10-20 nm of hydrodynamic diameter. This MMP-9
      triggered decrease in nanoparticle size also led to up to a six-fold decrease in
      nanoparticle internalization by macrophages and is observable by T(2)-weighted
      magnetic resonance imaging. These findings guide the design of imaging or
      therapeutic nanoparticles for in vivo targeting of macrophage activity in
      pathologic states.

PMID- 22359458
TI  - Impact of heat treatment on size, structure, and bioactivity of elemental
      selenium nanoparticles.
AB  - BACKGROUND: Elemental selenium nanoparticles have emerged as a novel selenium
      source with the advantage of reduced risk of selenium toxicity. The present work
      investigated whether heat treatment affects the size, structure, and bioactivity
      of selenium nanoparticles. METHODS AND RESULTS: After a one-hour incubation of
      solution containing 80 nm selenium particles in a 90 degrees C water bath, the
      nanoparticles aggregated into larger 110 nm particles and nanorods (290 nm * 70
      nm), leading to significantly reduced bioavailability and phase II enzyme
      induction in selenium-deficient mice. When a solution containing 40 nm selenium
      nanoparticles was treated under the same conditions, the nanoparticles aggregated
      into larger 72 nm particles but did not transform into nanorods, demonstrating
      that the thermostability of selenium nanoparticles is size-dependent, smaller
      selenium nanoparticles being more resistant than larger selenium nanoparticles to
      transformation into nanorods during heat treatment. CONCLUSION: The present
      results suggest that temperature and duration of the heat process, as well as the
      original nanoparticle size, should be carefully selected when a solution
      containing selenium nanoparticles is added to functional foods.

PMID- 22359459
TI  - Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for
      cellular attachment and entry of hepatitis B virus.
AB  - Overexpression of squamous cell carcinoma antigen 1 (SCCA1) in hepatitis G2
      (HepG2) and Chinese hamster ovary cells can increase hepatitis B virus (HBV)
      binding capacity by interacting with the preS1 domain of the HBV surface antigen.
      However, the magnitude of increase in binding capacity was higher by several
      orders in the former, indicating the existence of additional factor(s) produced
      by HepG2 cells, which facilitates HBV attachment. Ferritin light chain (FTL) was
      identified as the sole high hit candidate by screening human liver cDNA library
      using a bacterial two-hybrid system with either preS or SCCA1 as the bait.
      Subsequent in vitro protein-protein interaction assays confirmed the binding
      activity of FTL to both preS and SCCA1, as well as the formation of triple
      complex preS-FTL-SCCA1, and narrowed down the binding sites on FTL. In vitro
      overexpression of FTL could further enhance HBV attachment in both HepG2 and
      Chinese hamster ovary cells, which were already overexpressing SCCA1.
      Importantly, in vivo co-expression of human FTL and SCCA1 in mouse liver by means
      of tailvein hydrodynamic injection increased serum levels of HBV surface antigen
      transiently 24 hours post challenge with HBV-positive human sera, and a large
      amount of HBV core antigen-positive hepatocytes around blood vessels could be
      identified by immunohistochemical staining 48 hours post challenge. The data
      strongly suggest that FTL and SCCA1 may serve as coreceptors in HBV cellular
      attachment and virus entry into hepatocytes.

PMID- 22359460
TI  - Surface decoration by Spirulina polysaccharide enhances the cellular uptake and
      anticancer efficacy of selenium nanoparticles.
AB  - A simple and solution-phase method for functionalization of selenium
      nanoparticles (SeNPs) with Spirulina polysaccharides (SPS) has been developed in
      the present study. The cellular uptake and anticancer activity of SPS-SeNPs were
      also evaluated. Monodisperse and homogeneous spherical SPS-SeNPs with diameters
      ranging from 20 nm to 50 nm were achieved under optimized conditions, which were
      stable in the solution phase for at least 3 months. SPS surface decoration
      significantly enhanced the cellular uptake and cytotoxicity of SeNPs toward
      several human cancer cell lines. A375 human melanoma cells were found extremely
      susceptible to SPS-SeNPs with half maximal (50%) inhibitory concentration value
      of 7.94 MUM. Investigation of the underlying mechanisms revealed that SPS-SeNPs
      inhibited cancer cell growth through induction of apoptosis, as evidenced by an
      increase in sub-G(1) cell population, deoxyribonucleic acid fragmentation,
      chromatin condensation, and phosphatidylserine translocation. Results suggest
      that the strategy to use SPS as a surface decorator could be an effective way to
      enhance the cellular uptake and anticancer efficacy of nanomaterials. SPS-SeNPs
      may be a potential candidate for further evaluation as a chemopreventive and
      chemotherapeutic agent against human cancers.

PMID- 22359462
TI  - Extended scope physiotherapy roles for orthopedic outpatients: an update
      systematic review of the literature.
AB  - PURPOSE: This systematic review updates one conducted in 2008 into extended scope
      practice (ESP) in physiotherapy in orthopedics. METHODS: A comprehensive open
      ended search was conducted using electronic library data-bases and Google Scholar
      to identify any primary study design reporting on physiotherapists working in ESP
      roles within orthopedic settings. Studies were allocated to the National Health
      and Medical Research Council hierarchy of evidence, although only studies in
      levels I, II, or III_1 were critically appraised using a purpose-built critical
      appraisal tool. Information was extracted on the country of origin, ESP tasks,
      relevant training, patient types, health, process, and cost measures. RESULTS:
      1071 studies were identified, and twelve were included in the review (including
      diagnostic and evaluative research). The hierarchy of evidence ranged from II to
      IV, from which only two diagnostic studies met the criteria for critical
      appraisal. ESP tasks included injection therapy, removing k-wires, and requesting
      investigations. The education of ESP physiotherapists varied widely, and included
      formal and informal training. The positive outcomes of ESP initiatives were
      reported, in diagnostic ability, reduced costs and waiting times, and improved
      health outcomes. CONCLUSION: Despite the positive results, the generally low
      level of evidence and the range of outcome measures reported, constrained clear
      conclusions regarding the health, process, and cost implications of ESP
      physiotherapy roles in orthopedic settings. The need for formalized, widely
      recognized training was highlighted, to give ESP physiotherapy roles credibility.

PMID- 22359463
TI  - Health expenditure comparison of extended-release metoprolol succinate and
      immediate-release metoprolol tartarate.
AB  - BACKGROUND: Metoprolol, a selective beta-1 blocker, is available in two different
      salt forms in the market - metoprolol succinate (MS) and metoprolol tartarate
      (MT). Both the formulations are Food and Drug Administration approved for the
      treatment of hypertension. Several studies have shown similar efficacies between
      the two salts; however, they differ in their pharmacokinetic properties and are
      therefore priced differently. The primary objective of this study was to compare
      the overall health care expenditures of hypertensive patients on MT and MS to see
      if the price difference in the two preparations is offset by savings in overall
      expenditure. METHODS: Two cohorts of patients using MT and MS were selected from
      the 2008 Medical Expenditure Panel Survey. Propensity score matching technique
      was used to balance the cohorts on various parameters such as demographic
      information, insurance status, and comorbidity score. Patients using MT were
      matched to patients using MS on the logit of propensity score using calipers of
      width equal to 0.2 of the standard deviation of the logit of the propensity
      score. Multiple regression analysis was carried out to examine the association
      between health expenditure and type of metoprolol salt, adjusting for other
      covariates. RESULTS: A total of 742 patients were found to use metoprolol (MT
      388, MS-354). After propensity score matching, a total of 582 patients were left
      in the sample for final analysis (291 patients in each cohort). The average
      annual health care expenditure was slightly higher in the MT cohort; however,
      after adjusting for covariates in a multivariate analysis, the difference was
      found to be statistically insignificant (P = 0.23). CONCLUSION: Both the products
      of metoprolol were found to have similar average annual total health care
      expenditure; however, MS once a day has higher out-of-pocket cost.

PMID- 22359461
TI  - Bone integration capability of nanopolymorphic crystalline hydroxyapatite coated
      on titanium implants.
AB  - The mechanism by which hydroxyapatite (HA)-coated titanium promotes bone-implant
      integration is largely unknown. Furthermore, refining the fabrication of nano
      structured HA to the level applicable to the mass production process for titanium
      implants is challenging. This study reports successful creation of
      nanopolymorphic crystalline HA on microroughened titanium surfaces using a
      combination of flame spray and low-temperature calcination and tests its
      biological capability to enhance bone-implant integration. Sandblasted
      microroughened titanium implants and sandblasted + HA-coated titanium implants
      were subjected to biomechanical and histomorphometric analyses in a rat model.
      The HA was 55% crystallized and consisted of nanoscale needle-like architectures
      developed in various diameters, lengths, and orientations, which resulted in a
      70% increase in surface area compared to noncoated microroughened surfaces. The
      HA was free from impurity contaminants, with a calcium/phosphorus ratio of 1.66
      being equivalent to that of stoichiometric HA. As compared to microroughened
      implants, HA-coated implants increased the strength of bone-implant integration
      consistently at both early and late stages of healing. HA-coated implants showed
      an increased percentage of bone-implant contact and bone volume within 50 MUm
      proximity of the implant surface, as well as a remarkably reduced percentage of
      soft tissue intervention between bone and the implant surface. In contrast, bone
      volume outside the 50 MUm border was lower around HA-coated implants. Thus, this
      study demonstrated that the addition of pure nanopolymorphic crystalline HA to
      microroughened titanium not only accelerates but also enhances the level of bone
      implant integration and identified the specific tissue morphogenesis parameters
      modulated by HA coating. In particular, the nanocrystalline HA was proven to be
      drastic in increasing osteoconductivity and inhibiting soft tissue infiltration,
      but the effect was limited to the immediate microenvironment surrounding the
      implant.

PMID- 22359464
TI  - Are Toll-like receptor gene polymorphisms associated with prostate cancer?
AB  - The suggestion that there is a connection between chronic intraprostatic
      inflammation and prostate cancer was declared some years ago. As Toll-like
      receptors (TLRs) are the key players in the processes of chronic intraprostatic
      inflammation, there is a hypothesis that TLR gene polymorphisms may be associated
      with prostate cancer risk. Although a number of comprehensive studies have been
      conducted on large samples in various countries, reliable connections between
      these single nucleotide polymorphisms and prostate cancer risk, stage, grade,
      aggressiveness, ability to metastasize, and mortality have not been detected.
      Results have also varied slightly in different populations. The data obtained
      regarding the absence of connection between the polymorphisms of the genes
      encoding interleukin-1 receptor-associated kinases (IRAK1 and IRAK4) and prostate
      cancer risk might indicate a lack of association between inherited variation in
      the TLR signaling pathway and prostate cancer risk. It is possible to consider
      that polymorphisms of genes encoding TLRs and proteins of the TLR pathway also do
      not play a major role in the etiology and pathogenesis of prostate cancer.
      Feasibly, it would be better to focus research on associations between TLR single
      nucleotide polymorphisms and cancer risk in other infection-related cancer types.

PMID- 22359465
TI  - Reproductive health options among HIV-infected persons in the low-income Niger
      Delta of Nigeria.
AB  - BACKGROUND: With the advent and widespread use of highly active antiretroviral
      therapy for the treatment of human immunodeficiency virus (HIV), persons living
      with HIV/acquired immune deficiency syndrome (AIDS) are living good quality,
      longer, and healthier lives. Many couples affected by HIV, both serodiscordant
      and seroconcordant, are beginning to consider options for safer reproduction. The
      aim of this study was to assess the reproductive health concerns among persons
      living with HIV/AIDS in the Niger Delta of Nigeria. METHODS AND RESULTS: The
      subjects were aged 18-58 (mean 41.25 +/- 11.50) years, with 88 males (45.1%) and
      107 females (54.9). Of the 195 subjects studied, 111 (56.9%) indicated a desire
      to have children. The main reasons for wanting to procreate included ensuring
      lineage continuity and posterity (52.3%), securing relationships (27.0%), and
      pressure from relatives to reproduce (20.7%). Single subjects were more inclined
      to have children (76.3%) compared with married (51.5%), widowed (18.2%), and
      separated/divorced subjects (11.1%, P = 0.03). Of the 111 subjects who indicated
      their desire to have children, women were more inclined to have children (64.5%)
      than men (47.7%). The major concern among the 84 (43.1%) subjects not desiring
      more children were the fear of infecting a serodiscordant partner and baby
      (57.1%), fear of dying and leaving behind orphans (28.6%), and fear that they may
      become too ill and unable to support the child financially (14.3%). Persons with
      no formal education were more likely to have children irrespective of their
      positive HIV status (66.7%) than persons educated to tertiary education level
      (37.0%, P = 0.01). Of 111 subjects who desired to have children, only 58% had
      attended reproductive health counseling with HIV counselors. Reasons for not
      seeking advice were anticipated negative reactions and discrimination from
      counselors. A significant number of subjects were only aware of some of the
      reproductive health options available to reduce the risk of infecting their
      partners and/or baby, such as artificial vaginal insemination, intrauterine
      insemination, cesarean section, avoidance of breast feeding, and offering
      prenatal pre-exposure prophylaxis to the fetus. They were unaware of other
      options, such as sperm washing, in vitro fertilization, and intracytoplasmic
      sperm injection. Of the 43.1% not anticipating more children, 36.9% were
      anticipating adoption. CONCLUSION: Our study has shown that a significant number
      of HIV-infected persons in the Niger Delta of Nigeria desire to have children
      irrespective of their positive serostatus. There is the need to support the
      sexual and reproductive rights of HIV-infected individuals. Additional training
      needs to be offered to HIV counselors on evidence-based best and affordable
      practices regarding reproductive health issues among persons living with HIV.
      Policies that support availability and accessibility to relevant reproductive and
      sexual health services, including contraception and procreation, need to be
      developed. Public enlightenment programs on HIV are needed to reduce the
      stigmatization that HIV-infected persons face from family members and their
      communities.

PMID- 22359466
TI  - Nortriptyline versus fluoxetine in the treatment of major depressive disorder: a
      six-month, double-blind clinical trial.
AB  - BACKGROUND: Depression is a common psychiatric disorder worldwide, including in
      Iran, and is estimated to affect 10%-15% of the population. Antidepressant drugs
      can have multiple side effects, so a good choice of drug is important for
      successful treatment. This study compared the efficacy of nortriptyline with that
      of fluoxetine in the treatment of patients with major depressive disorder and
      assessed related factors, including age, gender, and level of education. METHODS:
      The study was a double-blind, randomized clinical trial with a six-month follow
      up period. Participants were 120 patients aged 15-60 years with a diagnosis of
      major depressive disorder based on a psychiatry interview and the Beck depression
      rating scale, which were performed at the beginning, middle, and end of the
      study. The patients were treated with nortriptyline or fluoxetine. The paired t
      test, independent t-test, and the k chi-square test were used to analyze the
      data. RESULTS: Twenty-three patients dropped out and 97 remained in the trial.
      Before intervention, the mean depression score was 32.85 +/- 6.23 in the
      nortriptyline group and 33.12 +/- 6.50 in the fluoxetine group. The results of
      the independent t-test showed a significant difference between depression score
      means before and after treatment in both groups. Changes at the end of the trial
      compared with baseline scores were 13.4 +/- 4.68 and 16.96 +/- 4.96 for
      nortriptyline and fluoxetine, respectively. Paired t-testing showed a significant
      difference in the mean depression score for both the nortriptyline and fluoxetine
      groups. Age, gender, and level of education had no significant effects on the
      outcome of treatment in the two groups. CONCLUSION: The present study suggests
      that both nortriptyline and fluoxetine were effective in the treatment of
      depression, but that fluoxetine was more effective than nortriptyline after 3 and
      6 months of treatment.

PMID- 22359467
TI  - The evolution of humor from male aggression.
AB  - The response to seeing a man riding a unicycle was reported to be consistently
      related to the viewer's sex and stage of physical development. To see if this
      observation was universal, observations of responses were collected from 23 male
      and 9 female unicyclists aged 15-69 years, with 2-40 years cycling experience
      across four continents. With two exceptions among men, the findings were the same
      as those originally reported: children showed interest and curiosity, young girls
      showed little interest, while adult women showed a kindly, concerned, praising
      response. By contrast, boys showed physical aggression, which became more verbal,
      merging in the later teens to the snide, aggressive, stereotyped humorous
      response shown by adult males, which became less frequent in elderly men. The
      universality of the response across different individuals, environments, and
      dates of observation suggests an endogenous mechanism, and the association with
      masculine development relates this to androgen. The theoretical consequences are
      discussed. It is concluded that humor develops from aggression in males and is
      evolutionarily related to sexual selection.

PMID- 22359468
TI  - The Protective Effect of Quercetin-3-O-beta-D-Glucuronopyranoside on Ethanol
      induced Damage in Cultured Feline Esophageal Epithelial Cells.
AB  - Quercetin-3-O-beta-D-glucuronopyranoside (QGC) is a flavonoid glucoside extracted
      from Rumex Aquaticus Herba. We aimed to explore its protective effect against
      ethanol-induced cell damage and the mechanism involved in the effect in feline
      esophageal epithelial cells (EEC). Cell viability was tested and 2',7'
      dichlorofluorescin diacetate assay was used to detect intracellular H(2)O(2)
      production. Western blotting analysis was performed to investigate MAPK
      activation and interleukin 6 (IL-6) expression. Exposure of cells to 10% ethanol
      time-dependently decreased cell viability. Notably, exposure to ethanol for 30
      min decreased cell viability to 43.4%. When cells were incubated with 50 uM QGC
      for 12 h prior to and during ethanol treatment, cell viability was increased to
      65%. QGC also inhibited the H(2)O(2) production and activation of ERK 1/2 induced
      by ethanol. Pretreatment of cells with the NADPH oxidase inhibitor, diphenylene
      iodonium, also inhibited the ethanol-induced ERK 1/2 activation. Treatment of
      cells with ethanol for 30 or 60 min in the absence or presence of QGC exhibited
      no changes in the IL-6 expression or release compared to control. Taken together,
      the data indicate that the cytoprotective effect of QGC against ethanol-induced
      cell damage may involve inhibition of ROS generation and downstream activation of
      the ERK 1/2 in feline EEC.

PMID- 22359469
TI  - Chronic Opium Treatment Can Differentially Induce Brain and Liver Cells Apoptosis
      in Diabetic and Non-diabetic Male and Female Rats.
AB  - It has been shown that some opium derivatives promote cell death via apoptosis.
      This study was designed to examine the influence of opium addiction on brain and
      liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats.
      This experimental study was performed on normal, opium-addicted, diabetic and
      diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL
      and DNA fragmentation assays. Results of this study showed that apoptosis in
      opium-addicted and diabetic opium-addicted brain and liver cells were
      significantly higher than the both normal and diabetic rats. In addition, we
      found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted
      male rats were significantly higher than opium-addicted and diabetic opium
      addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic
      opium-addicted female rats were significantly higher than opium-addicted and
      diabetic opium-addicted male. Overall, these results indicate that opium probably
      plays an important role in brain and liver cells apoptosis, therefore, leading
      neurotoxicity and hepatotoxicity. These findings also in away possibly means that
      male brain cells are more susceptible than female and interestingly liver of
      females are more sensitive than males in induction of apoptosis by opium.

PMID- 22359470
TI  - The Protective Effect of Black Ginseng Against Transient Focal Ischemia-induced
      Neuronal Damage in Rats.
AB  - Black ginseng (BG) has been widely used as herbal treatment for improving
      physiological function. In order to investigate the neuroprotective action of
      this herbal medicine, we examined the influence of BG on the learning and memory
      of rats using the Morris water maze, and we studied the effects of BG on the
      central cholinergic system and neural nitric oxide synthesis in the hippocampus
      of rats with neuronal and cognitive impairment. After middle cerebral artery
      occlusion was applied for 2h, the rats were administered BG (100 or 400 mgkg(-1),
      p.o.) daily for 2 weeks, followed by training and performance of the Morris water
      maze test. The rats with ischemic insults showed impaired learning and memory on
      the tasks. Treatment with BG produced improvement in the escape latency to find
      the platform. Further, the BG groups showed a reduced loss of cholinergic
      immunoreactivity and nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPH-d)-positive neurons in the hippocampus compared to that of the ISC group.
      These results demonstrated that BG has a protective effect against ischemia
      induced neuronal and cognitive impairment. Our results suggest that BG might be
      useful for the treatment of vascular dementia.

PMID- 22359471
TI  - Vasorelaxing Activity of Ulmus davidiana Ethanol Extracts in Rats: Activation of
      Endothelial Nitric Oxide Synthase.
AB  - Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree
      widespread in northeast Asia. It is traditionally used for anticancer and anti
      inflammatory therapy. The present study investigated the effect of an ethanol
      extract of UD on vascular tension and its underlying mechanism in rats. The dried
      root bark of UD was ground and extracted with 80% ethanol. The prepared UD
      extract was used in further analysis. The effect of UD on the cell viability,
      vasoreactivity and hemodynamics were investigated using propidium iodide staining
      in cultured cells, isometric tension recording and blood pressure analysis,
      respectively. Low dose of UD (10~100ug/ml) did not affect endothelial cell
      viability, but high dose of UD reduced cell viability. UD induced vasorelaxation
      in the range of 0.1~10ug/ml with an ED(50) value of 2ug/ml. UD-induced
      vasorelaxation was completely abolished by removal of the endothelium or by pre
      treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited
      calcium influx induced by phenylephrine and high K(+) and also completely
      abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100
      mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner.
      Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in
      anesthetized rats. However, UD-induced hypotensive actions were minimized in L
      NAME-treated rats. Taken together, out results showed that UD induced
      vasorelaxation and has antihypertensive properties, which may be due the
      activation of nitric oxide synthase in endothelium.

PMID- 22359472
TI  - 4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High
      Concentrations of Glucose in Human Gingival Fibroblasts.
AB  - High glucose leads to physio/pathological alterations in diabetes patients. We
      investigated collagen production in human gingival cells that were cultured in
      high concentrations of glucose. Collagen synthesis and secretion were increased
      when the cells were exposed to high concentrations of glucose. We examined
      endoplasmic reticulum (ER) stress response because glucose metabolism is related
      to ER functional status. An ER stress response including the expression of
      glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol
      requiring enzyme alpha (IRE-1alpha) and phosphoreukaryotic initiation factor
      alpha (p-eIF-2alpha) was activated in the presence of high glucose. Activating
      transcription factor 4 (ATF-4), a downstream protein of p-eIF-2alpha as well as a
      transcription factor for collagen, was also phosphorylated and translocalized
      into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response
      and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest
      that high concentrations of glucose-induced collagen are linked to ER stress and
      the associated phosphorylation and nuclear translocation of ATF-4.

PMID- 22359473
TI  - The Neuroprotective Potential of Cyanidin-3-glucoside Fraction Extracted from
      Mulberry Following Oxygen-glucose Deprivation.
AB  - In this study, cyanidin-3-glucoside (C3G) fraction extracted from the mulberry
      fruit (Morus alba L.) was investigated for its neuroprotective effects against
      oxygen-glucose deprivation (OGD) and glutamate-induced cell death in rat primary
      cortical neurons. Cell membrane damage and mitochondrial function were assessed
      by LDH release and MTT reduction assays, respectively. A time-course study of OGD
      induced cell death of primary cortical neurons at 7 days in vitro (DIV) indicated
      that neuronal death was OGD duration-dependent. It was also demonstrated that OGD
      for 3.5 h resulted in approximately 50% cell death, as determined by the LDH
      release assay. Treatments with mulberry C3G fraction prevented membrane damage
      and preserved the mitochondrial function of the primary cortical neurons exposed
      to OGD for 3.5 h in a concentration-dependent manner. Glutamate-induced cell
      death was more pronounced in DIV-9 and DIV-11 cells than that in DIV-7 neurons,
      and an application of 50uM glutamate was shown to induce approximately 40% cell
      death in DIV-9 neurons. Interestingly, treatment with mulberry C3G fraction did
      not provide a protective effect against glutamate-induced cell death in primary
      cortical neurons. On the other hand, treatment with mulberry C3G fraction
      maintained the mitochondrial membrane potential (MMP) in primary cortical neurons
      exposed to OGD as assessed by the intensity of rhodamine-123 fluorescence. These
      results therefore suggest that the neuroprotective effects of mulberry C3G
      fraction are mediated by the maintenance of the MMP and mitochondrial function
      but not by attenuating glutamate-induced excitotoxicity in rat primary cortical
      neurons.

PMID- 22359474
TI  - Inhibition of Inducible Nitric Oxide Synthase Attenuates Monosodium Urate-induced
      Inflammation in Mice.
AB  - The present study elucidated the effect of the selective inducible nitric oxide
      synthase (iNOS) inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) on monosodium
      urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10
      mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg)
      into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot
      thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling
      in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly
      suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO)
      metabolites and gene expression and protein level of iNOS in feet were increased
      by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was
      observed in nitrotyrosine level. MSU increased the gene expression of tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta and L-NIL pretreatment
      suppressed MSU-induced cytokines expression. The mRNA levels of superoxide
      dismutase and glutathione peroxidase1 were increased by MSU and L-NIL
      pretreatment normalized the gene expression. Phosphorylation of extracellular
      signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by
      L-NIL pretreatment. The mRNA levels of iNOS, TNF-alpha, and IL-1beta were
      increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal
      osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner.
      This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice
      feet suggesting that iNOS might be involved in MSU-induced inflammation.

PMID- 22359475
TI  - A Computational Model of the Temperature-dependent Changes in Firing Patterns in
      Aplysia Neurons.
AB  - We performed experiments using Aplysia neurons to identify the mechanism
      underlying the changes in the firing patterns in response to temperature changes.
      When the temperature was gradually increased from 11C to 31C the firing patterns
      changed sequentially from the silent state to beating, doublets, beating-chaos,
      bursting-chaos, square-wave bursting, and bursting-oscillation patterns. When the
      temperature was decreased over the same temperature range, these sequential
      changes in the firing patterns reappeared in reverse order. To simulate this
      entire range of spiking patterns we modified nonlinear differential equations
      that Chay and Lee made using temperature-dependent scaling factors. To refine the
      equations, we also analyzed the spike pattern changes in the presence of
      potassium channel blockers. Based on the solutions of these equations and
      potassium channel blocker experiments, we found that, as temperature increases,
      the maximum value of the potassium channel relaxation time constant, tau(n)(t)
      increases, but the maximum value of the probabilities of openings for activation
      of the potassium channels, n(t) decreases. Accordingly, the voltage-dependent
      potassium current is likely to play a leading role in the temperature-dependent
      changes in the firing patterns in Aplysia neurons.

PMID- 22359476
TI  - Role of regulators of g-protein signaling 4 in ca signaling in mouse pancreatic
      acinar cells.
AB  - Regulators of G-protein signaling (RGS) proteins are regulators of Ca(2+)
      signaling that accelerate the GTPase activity of the G-protein alpha-subunit.
      RGS1, RGS2, RGS4, and RGS16 are expressed in the pancreas, and RGS2 regulates G
      protein coupled receptor (GPCR)-induced Ca(2+) oscillations. However, the role of
      RGS4 in Ca(2+) signaling in pancreatic acinar cells is unknown. In this study, we
      investigated the mechanism of GPCR-induced Ca(2+) signaling in pancreatic acinar
      cells derived from RGS4(-/-) mice. RGS4(-/-) acinar cells showed an enhanced
      stimulus intensity response to a muscarinic receptor agonist in pancreatic acinar
      cells. Moreover, deletion of RGS4 increased the frequency of Ca(2+) oscillations.
      RGS4(-/-) cells also showed increased expression of sarco/endoplasmic reticulum
      Ca(2+) ATPase type 2. However, there were no significant alterations, such as
      Ca(2+) signaling in treated high dose of agonist and its related amylase
      secretion activity, in acinar cells from RGS4(-/-) mice. These results indicate
      that RGS4 protein regulates Ca(2+) signaling in mouse pancreatic acinar cells.

PMID- 22359477
TI  - Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression
      of Cocaine-induced Behavioral Sensitization in Rats.
AB  - Repeated administration of psychostimulants such as cocaine leads to the
      development of behavioral sensitization. Extracellular signal-Regulated Kinase
      (ERK), an enzyme important for long-term neuronal plasticity, has been implicated
      in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site
      mediating the expression of behavioral sensitization by drugs of abuse, the
      precise role of ERK activation in this site has not been determined. In this
      study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single
      bilateral microinjections of PD98059 (0.5 or 2.0u g/side), or U0126 (0.1 or
      1.0ug/side), into this site dose-dependently inhibited the expression of cocaine
      induced behavioral sensitization when measured at day 7 following 6 consecutive
      daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle
      or PD98059 alone produced no different locomotor activity compared to saline
      control. Further, microinjection of PD98059 (2.0u g/side) in the NAcc
      specifically lowered cocaine-induced increase of ERK phosphorylation levels in
      this site, while unaffecting p-38 protein levels. These results indicate that ERK
      activation in the NAcc is necessary for the expression of cocaine-induced
      behavioral sensitization, and further suggest that repeated cocaine evokes
      neuronal plasticity involving ERK pathway in this site leading to long-lasting
      behavioral changes.

PMID- 22359479
TI  - Nitric Oxide-mediated Relaxation by High K in Human Gastric Longitudinal Smooth
      Muscle.
AB  - This study was designed to elucidate high-K(+)induced response of circular and
      longitudinal smooth muscle from human gastric corpus using isometric contraction.
      Contraction from circular and longitudinal muscle stripes of gastric corpus
      greater curvature and lesser curvature were compared. Circular smooth muscle from
      corpus greater curvature showed high K(+) (50 mM)-induced tonic contraction. On
      the contrary, however, longitudinal smooth muscle strips showed high K(+) (50 mM)
      induced sustained relaxation. To find out the reason for the discrepancy we
      tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA
      inhibitor, and KT5823, PKG inhibitor, did not affect high K(+)-induced
      relaxation. K(+) channel blockers like tetraethylammonium (TEA), apamin (APA),
      glibenclamide (Glib) and barium (Ba(2+)) also had no effect. However, N(G)-nitro
      L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an
      inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage
      dependent K(+) channel (K(V)) blocker, inhibited high K(+)-induced relaxation,
      hence reversing to tonic contraction. High K(+)-induced relaxation was observed
      in gastric corpus of human stomach, but only in the longitudinal muscles from
      greater curvature not lesser curvature. L-NNA, ODQ and K(V) channel blocker
      sensitive high K(+)-induced relaxation in longitudinal muscle of higher portion
      of corpus was also observed. These results suggest that longitudinal smooth
      muscle from greater curvature of gastric corpus produced high K(+)-induced
      relaxation which was activated by NO/sGC pathway and by K(V) channel dependent
      mechanism.

PMID- 22359478
TI  - Cigarette Smoke Extract-induced Reduction in Migration and Contraction in Normal
      Human Bronchial Smooth Muscle Cells.
AB  - The proliferation, migration, cytokine release, and contraction of airway smooth
      muscle cells are key events in the airway remodeling process that occur in lung
      disease such as asthma, chronic obstruction pulmonary disease, and cancer. These
      events can be modulated by a number of factors, including cigarette smoke extract
      (CSE). CSE-induced alterations in the viability, migration, and contractile
      abilities of normal human airway cells remain unclear. This study investigated
      the effect of CSE on cell viability, migration, tumor necrosis factor (TNF)-alpha
      secretion, and contraction in normal human bronchial smooth muscle cells
      (HBSMCs). Treatment of HBSMCs with 10% CSE induced cell death, and the death was
      accompanied by the generation of reactive oxygen species (ROS). CSE-induced cell
      death was reduced by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition,
      CSE reduced the migration ability of HBSMCs by 75%. The combination of NAC with
      CSE blocked the CSE-induced reduction of cell migration. However, CSE had no
      effect on TNF-alpha secretion and NF-kappaB activation. CSE induced an increase
      in intracellular Ca(2+) concentration in 64% of HBSMCs. CSE reduced the
      contractile ability of HBSMCs, and the ability was enhanced by NAC treatment.
      These results demonstrate that CSE treatment induces cell death and reduces
      migration and contraction by increasing ROS generation in normal HBSMCs. These
      results suggest that CSE may induce airway change through cell death and
      reduction in migration and contraction of normal HBSMCs.

PMID- 22359480
TI  - Spontaneous Oscillatory Rhythm in Retinal Activities of Two Retinal Degeneration
      (rd1 and rd10) Mice.
AB  - Previously, we reported that besides retinal ganglion cell (RGC) spike, there is
      ~ 10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal
      degeneration model, rd1 mice. The more recently identified rd10 mice have a later
      onset and slower rate of photoreceptor degeneration than the rd1 mice, providing
      more therapeutic potential. In this study, before adapting rd10 mice as a new
      animal model for our electrical stimulation study, we investigated electrical
      characteristics of rd10 mice. From the raw waveform of recording using 8*8
      microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP
      were isolated by using different filter setting. Fourier transform was performed
      for detection of frequency of bursting RGC spikes and oscillatory field potential
      (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always
      phase-locked with the OFP and this phase-locking property is preserved regardless
      of postnatal ages. However, in rd10 mice, there is a strong phase-locking
      tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first
      peak of OFP (~5 Hz) across different age groups. But this phase-locking property
      is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and
      rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5
      Hz), we expect different response patterns to electrical stimulus between rd1 and
      rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina,
      first we might define selection criteria for responding rd10 ganglion cells to
      electrical stimulus.

PMID- 22359481
TI  - Cytotoxicities and Quantitative Structure Activity Relationships of B13
      Sulfonamides in HT-29 and A549 Cells.
AB  - B13 analogues are being considered as therapeutic agents for cancer cells, since
      B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer
      cells. B13 sulfonamides are assumed to have biological activity similar to B13,
      since they are made by bioisosterically substituting the carboxyl moiety of B13
      with sulfone group. Twenty B13 sulfonamides were evaluated for their in vitro
      cytotoxicities against human colon cancer HT-29 and lung cancer A549 cell lines
      using MTT assays. Replacement of the amide group with a sulfonamide group
      increased cytotoxicity in both cancer cell lines. The sulfonamides with long
      alkyl chains exhibited activities two to three times more potent than that of B13
      and compound (15) had the most potent activity with IC(50) values of 27 and
      28.7uM for HT-29 and A549, respectively. The comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used
      to carry out QSAR molecular modeling of these compounds. The predictive CoMSIA
      models for HT-29 and A549 gave cross-validated q2 values of 0.703 and 0.830,
      respectively. From graphical analysis of these models, we suppose that the
      stereochemistry of 1,3-propandiol is not important for activity and that
      introduction of a sulfonamide group and long alkyl chains into B13 can increase
      cytotoxicity.

PMID- 22359482
TI  - Alteration of Ryanodine-receptors in Cultured Rat Aortic Smooth Muscle Cells.
AB  - Vascular smooth muscle cells can obtain a proliferative function in environments
      such as atherosclerosis in vivo or primary culture in vitro. Proliferation of
      vascular smooth muscle cells is accompanied by changes in ryanodine receptors
      (RyRs). In several studies, the cytosolic Ca(2+) response to caffeine is
      decreased during smooth muscle cell culture. Although caffeine is commonly used
      to investigate RyR function because it is difficult to measure Ca(2+) release
      from the sarcoplasmic reticulum (SR) directly, caffeine has additional off-target
      effects, including blocking inositol trisphosphate receptors and store-operated
      Ca(2+) entry. Using freshly dissociated rat aortic smooth muscle cells (RASMCs)
      and cultured RASMCs, we sought to provide direct evidence for the operation of
      RyRs through the Ca(2+)- induced Ca(2+)-release pathway by directly measuring
      Ca(2+) release from SR in permeabilized cells. An additional goal was to
      elucidate alterations of RyRs that occurred during culture. Perfusion of
      permeabilized, freshly dissociated RASMCs with Ca(2+) stimulated Ca(2+) release
      from the SR. Caffeine and ryanodine also induced Ca(2+) release from the SR in
      dissociated RASMCs. In contrast, ryanodine, caffeine and Ca(2+) failed to trigger
      Ca(2+) release in cultured RASMCs. These results are consistent with results
      obtained by immunocytochemistry, which showed that RyRs were expressed in
      dissociated RASMCs, but not in cultured RASMCs. This study is the first to
      demonstrate Ca(2+) release from the SR by cytosolic Ca(2+) elevation in vascular
      smooth muscle cells, and also supports previous studies on the alterations of
      RyRs in vascular smooth muscle cells associated with culture.

PMID- 22359483
TI  - c-Fos Expression in the Nucleus of the Solitary Tract in Response to Salt
      Stimulation in Rats.
AB  - Salt signals in tongue are relayed to the nucleus of the solitary tract (NST).
      This signaling is very important to determine whether to swallow salt-related
      nutrition or not and suggests some implications in discrimination of salt
      concentration. Salt concentration-dependent electrical responses in the chorda
      tympani and the NST were well reported. But salt concentration-dependency and
      spatial distribution of c-Fos in the NST were not well established. In the
      present study, NaCl signaling in the NST was studied in urethane-anesthetized
      rats. The c-Fos immunoreactivity in the six different NST areas along the rostral
      caudal axis and six subregions in each of bilateral NST were compared between
      applications of distilled water and different concentrations of NaCl to the
      tongue of experimental animals. From this study, salt stimulation with high
      concentration (1.0 M NaCl) induced significantly higher c-Fos expression in
      intermediate NST and dorsal-medial and dorsal-middle subregions of the NST
      compared to distilled water stimulation. The result represents the specific
      spatial distribution of salt taste perception in the NST.

PMID- 22359484
TI  - Abdominal multiple splenosis mimicking liver and colon tumors: a case report and
      review of the literature.
AB  - Splenosis is not an uncommon disease. However, it is often misdiagnosed as
      malignant tumors, and then the patients underwent unnecessary operations.
      Unfortunately, it is very difficult to diagnose it prior to operation. We report
      a rare case of a 49-year-old female patient with liver and colon splenosis,
      misdiagnosed as liver and colon tumors, and summarize experience how to diagnose
      it preoperatively according to literatures. We come to conclusion that in
      patients who ever underwent splenectomy especially owning to trauma, and were
      found mass in abdomen, clinicians must consider the existence of splenosis, and
      take some measures, such as scintigraphy with (99m) Tc labelled heat-denatured
      erythrocyte rather than biopsy, to diagnose it correctly to prevent unnecessary
      operations.

PMID- 22359485
TI  - Effects of a sliding plate on morphology of the epiphyseal plate in goat distal
      femur.
AB  - The aim of this study was to observe the effects of a sliding plate on the
      morphology of the epiphyseal plate in goat distal femur. Eighteen premature
      female goats were divided randomly into sliding plate, regular plate and control
      groups. Radiographic analysis and histological staining were performed to
      evaluate the development of epiphyseal plate at 4 and 8 weeks after surgery. In
      the sliding plate group, the plate extended accordingly as the epiphyseal plate
      grows, and the epiphyseal morphology was kept essential normal. However, the
      phenomenon of the epiphyseal growth retardation and premature closure were very
      common in the regular plate group. In addition, the sliding plate group exhibited
      more normal histologic features and Safranin O staining compared to the regular
      plate group. Our results suggest that the sliding plate can provide reliable
      internal fixation of epiphyseal fracture without inhibiting epiphyseal growth.

PMID- 22359486
TI  - Effect of bone morphogenetic protein-2 on proliferation and apoptosis of gastric
      cancer cells.
AB  - OBJECTIVE: To investigate the effects of bone morphogenetic protein-2 (BMP-2) on
      the proliferation, differentiation and apoptosis of normal human gastric mucosal
      cells and gastric cancer cells. METHODS: Poorly differentiated gastric cancer
      BGC823 cells, moderately differentiated gastric cancer cells and normal human
      gastric mucosal epithelial GES-1 cells were independently treated with
      recombinant human BMP-2 or its inhibitor Noggin. MTT assay was performed to
      detect the proliferation, flow cytometry done to measure the cell cycle and
      apoptosis and immunohistochemistry carried out to determine the expression of
      cyclin-dependent kinase 4 (CDK4). RESULTS: BMP-2 exerted inhibitory effect on the
      growth of all types of cells and the inhibition become more evident with the
      increase of BMP-2 dose. After treatment with 200 ng/ml BMP-2, cancer cells
      arrested in G1 phase and those in S phase reduced. Gastric cancer cells had
      higher CDK4 expression than GES-1 cells. BMP-2 decreased CDK-4 expression in
      cancer cells but had no influence in GES-1 cells. Noggin conferred promotive
      effect on the growth of 3 types of cells. In 2 types of cancer cells, treatment
      with 2000 ng/ml Noggin significantly increased the proportion of cells in S phase
      but reduced that in G1 phase. However, Noggin did not affect the cell cycle of
      GES-1 cells. The CDK4 expression was markedly increased in 2 types of cancer
      cells but that of GES-1 remained unchanged after treatment with 2000 ng/ml
      Noggin. CONCLUSIONS: BMP-2 may inhibit the proliferation of both normal and
      malignant gastric epithelial cells, down-regulate CDK4 expression in gastric
      cancer cells and arrest gastric cancer cells in G1-phase in cell cycle. Through
      antagonizing BMP-2, Noggin, may accelerate the proliferation of gastric cancer
      cells. Thus, the abnormality of BMP signaling pathway may play an important role
      in the pathogenesis of gastric cancer.

PMID- 22359487
TI  - On the effect of thermodynamic equilibrium on the assembly efficiency of complex
      multi-layered virus-like particles (VLP): the case of rotavirus VLP.
AB  - Previous studies have reported the production of malformed virus-like-particles
      (VLP) in recombinant host systems. Here we computationally investigate the case
      of a large triple-layered rotavirus VLP (RLP). In vitro assembly, disassembly and
      reassembly data provides strong evidence of microscopic reversibility of RLP
      assembly. Light scattering experimental data also evidences a slow and reversible
      assembly untypical of kinetic traps, thus further strengthening the fidelity of a
      thermodynamically controlled assembly. In silico analysis further reveals that
      under favourable conditions particles distribution is dominated by structural
      subunits and completely built icosahedra, while other intermediates are present
      only at residual concentrations. Except for harshly unfavourable conditions,
      assembly yield is maximised when proteins are provided in the same VLP protein
      mass composition. The assembly yield decreases abruptly due to thermodynamic
      equilibrium when the VLP protein mass composition is not obeyed. The latter
      effect is more pronounced the higher the Gibbs free energy of subunit association
      is and the more complex the particle is. Overall this study shows that the
      correct formation of complex multi-layered VLPs is restricted to a narrow range
      of association energies and protein concentrations, thus the choice of the host
      system is critical for successful assembly. Likewise, the dynamic control of
      intracellular protein expression rates becomes very important to minimize wasted
      proteins.

PMID- 22359488
TI  - Dynamic energy landscapes of riboswitches help interpret conformational
      rearrangements and function.
AB  - Riboswitches are RNAs that modulate gene expression by ligand-induced
      conformational changes. However, the way in which sequence dictates alternative
      folding pathways of gene regulation remains unclear. In this study, we compute
      energy landscapes, which describe the accessible secondary structures for a range
      of sequence lengths, to analyze the transcriptional process as a given sequence
      elongates to full length. In line with experimental evidence, we find that most
      riboswitch landscapes can be characterized by three broad classes as a function
      of sequence length in terms of the distribution and barrier type of the
      conformational clusters: low-barrier landscape with an ensemble of different
      conformations in equilibrium before encountering a substrate; barrier-free
      landscape in which a direct, dominant "downhill" pathway to the minimum free
      energy structure is apparent; and a barrier-dominated landscape with two isolated
      conformational states, each associated with a different biological function.
      Sharing concepts with the "new view" of protein folding energy landscapes, we
      term the three sequence ranges above as the sensing, downhill folding, and
      functional windows, respectively. We find that these energy landscape patterns
      are conserved in various riboswitch classes, though the order of the windows may
      vary. In fact, the order of the three windows suggests either kinetic or
      thermodynamic control of ligand binding. These findings help understand
      riboswitch structure/function relationships and open new avenues to riboswitch
      design.

PMID- 22359489
TI  - A race between tumor immunoescape and genome maintenance selects for optimum
      levels of (epi)genetic instability.
AB  - The human immune system functions to provide continuous body-wide surveillance to
      detect and eliminate foreign agents such as bacteria and viruses as well as the
      body's own cells that undergo malignant transformation. To counteract this
      surveillance, tumor cells evolve mechanisms to evade elimination by the immune
      system; this tumor immunoescape leads to continuous tumor expansion, albeit
      potentially with a different composition of the tumor cell population
      ("immunoediting"). Tumor immunoescape and immunoediting are products of an
      evolutionary process and are hence driven by mutation and selection. Higher
      mutation rates allow cells to more rapidly acquire new phenotypes that help evade
      the immune system, but also harbor the risk of an inability to maintain essential
      genome structure and functions, thereby leading to an error catastrophe. In this
      paper, we designed a novel mathematical framework, based upon the quasispecies
      model, to study the effects of tumor immunoediting and the evolution of
      (epi)genetic instability on the abundance of tumor and immune system cells. We
      found that there exists an optimum number of tumor variants and an optimum
      magnitude of mutation rates that maximize tumor progression despite an active
      immune response. Our findings provide insights into the dynamics of tumorigenesis
      during immune system attacks and help guide the choice of treatment strategies
      that best inhibit diverse tumor cell populations.

PMID- 22359490
TI  - Joint analysis of multiple metagenomic samples.
AB  - The availability of metagenomic sequencing data, generated by sequencing DNA
      pooled from multiple microbes living jointly, has increased sharply in the last
      few years with developments in sequencing technology. Characterizing the contents
      of metagenomic samples is a challenging task, which has been extensively
      attempted by both supervised and unsupervised techniques, each with its own
      limitations. Common to practically all the methods is the processing of single
      samples only; when multiple samples are sequenced, each is analyzed separately
      and the results are combined. In this paper we propose to perform a combined
      analysis of a set of samples in order to obtain a better characterization of each
      of the samples, and provide two applications of this principle. First, we use an
      unsupervised probabilistic mixture model to infer hidden components shared across
      metagenomic samples. We incorporate the model in a novel framework for studying
      association of microbial sequence elements with phenotypes, analogous to the
      genome-wide association studies performed on human genomes: We demonstrate that
      stratification may result in false discoveries of such associations, and that the
      components inferred by the model can be used to correct for this stratification.
      Second, we propose a novel read clustering (also termed "binning") algorithm
      which operates on multiple samples simultaneously, leveraging on the assumption
      that the different samples contain the same microbial species, possibly in
      different proportions. We show that integrating information across multiple
      samples yields more precise binning on each of the samples. Moreover, for both
      applications we demonstrate that given a fixed depth of coverage, the average per
      sample performance generally increases with the number of sequenced samples as
      long as the per-sample coverage is high enough.

PMID- 22359491
TI  - Branch mode selection during early lung development.
AB  - Many organs of higher organisms, such as the vascular system, lung, kidney,
      pancreas, liver and glands, are heavily branched structures. The branching
      process during lung development has been studied in great detail and is
      remarkably stereotyped. The branched tree is generated by the sequential, non
      random use of three geometrically simple modes of branching (domain branching,
      planar and orthogonal bifurcation). While many regulatory components and local
      interactions have been defined an integrated understanding of the regulatory
      network that controls the branching process is lacking. We have developed a
      deterministic, spatio-temporal differential-equation based model of the core
      signaling network that governs lung branching morphogenesis. The model focuses on
      the two key signaling factors that have been identified in experiments,
      fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH
      receptor patched (Ptc). We show that the reported biochemical interactions give
      rise to a Schnakenberg-type Turing patterning mechanisms that allows us to
      reproduce experimental observations in wildtype and mutant mice. The kinetic
      parameters as well as the domain shape are based on experimental data where
      available. The developed model is robust to small absolute and large relative
      changes in the parameter values. At the same time there is a strong regulatory
      potential in that the switching between branching modes can be achieved by
      targeted changes in the parameter values. We note that the sequence of different
      branching events may also be the result of different growth speeds: fast growth
      triggers lateral branching while slow growth favours bifurcations in our model.
      We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that
      correspond to the observed branching modes.

PMID- 22359492
TI  - Modeling cortisol dynamics in the neuro-endocrine axis distinguishes normal,
      depression, and post-traumatic stress disorder (PTSD) in humans.
AB  - Cortisol, secreted in the adrenal cortex in response to stress, is an informative
      biomarker that distinguishes anxiety disorders such as major depression and post
      traumatic stress disorder (PTSD) from normal subjects. Yehuda et al. proposed a
      hypothesis that, in humans, the hypersensitive hypothalamus-pituitary-adrenal
      (HPA) axis is responsible for the occurrence of differing levels of cortisol in
      anxiety disorders. Specifically, PTSD subjects have lower cortisol levels during
      the late subjective night in comparison to normal subjects, and this was assumed
      to occur due to strong negative feedback loops in the HPA axis. In the present
      work, to address this hypothesis, we modeled the cortisol dynamics using
      nonlinear ordinary differential equations and estimated the kinetic parameters of
      the model to fit the experimental data of three categories, namely, normal,
      depressed, and PTSD human subjects. We concatenated the subjects (n = 3) in each
      category and created a model subject (n = 1) without considering the patient-to
      patient variability in each case. The parameters of the model for the three
      categories were simultaneously obtained through global optimization. Bifurcation
      analysis carried out with the optimized parameters exhibited two supercritical
      Hopf points and, for the choice of parameters, the oscillations were found to be
      circadian in nature. The fitted kinetic parameters indicate that PTSD subjects
      have a strong negative feedback loop and, as a result, the predicted oscillating
      cortisol levels are extremely low at the nadir in contrast to normal subjects,
      albeit within the endocrinologic range. We also simulated the phenotypes for each
      of the categories and, as observed in the clinical data of PTSD patients, the
      simulated cortisol levels are consistently low at the nadir, and correspondingly
      the negative feedback was found to be extremely strong. These results from the
      model support the hypothesis that high stress intensity and strong negative
      feedback loop may cause hypersensitive neuro-endocrine axis that results in
      hypocortisolemia in PTSD.

PMID- 22359493
TI  - DOGS: reaction-driven de novo design of bioactive compounds.
AB  - We present a computational method for the reaction-based de novo design of drug
      like molecules. The software DOGS (Design of Genuine Structures) features a
      ligand-based strategy for automated 'in silico' assembly of potentially novel
      bioactive compounds. The quality of the designed compounds is assessed by a graph
      kernel method measuring their similarity to known bioactive reference ligands in
      terms of structural and pharmacophoric features. We implemented a deterministic
      compound construction procedure that explicitly considers compound
      synthesizability, based on a compilation of 25'144 readily available synthetic
      building blocks and 58 established reaction principles. This enables the software
      to suggest a synthesis route for each designed compound. Two prospective case
      studies are presented together with details on the algorithm and its
      implementation. De novo designed ligand candidates for the human histamine H4
      receptor and gamma-secretase were synthesized as suggested by the software. The
      computational approach proved to be suitable for scaffold-hopping from known
      ligands to novel chemotypes, and for generating bioactive molecules with drug
      like properties.

PMID- 22359494
TI  - Paradoxical evidence integration in rapid decision processes.
AB  - Decisions about noisy stimuli require evidence integration over time.
      Traditionally, evidence integration and decision making are described as a one
      stage process: a decision is made when evidence for the presence of a stimulus
      crosses a threshold. Here, we show that one-stage models cannot explain
      psychophysical experiments on feature fusion, where two visual stimuli are
      presented in rapid succession. Paradoxically, the second stimulus biases
      decisions more strongly than the first one, contrary to predictions of one-stage
      models and intuition. We present a two-stage model where sensory information is
      integrated and buffered before it is fed into a drift diffusion process. The
      model is tested in a series of psychophysical experiments and explains both
      accuracy and reaction time distributions.

PMID- 22359495
TI  - On the Use of Gene Ontology Annotations to Assess Functional Similarity among
      Orthologs and Paralogs: A Short Report.
AB  - A recent paper (Nehrt et al., PLoS Comput. Biol. 7:e1002073, 2011) has proposed a
      metric for the "functional similarity" between two genes that uses only the Gene
      Ontology (GO) annotations directly derived from published experimental results.
      Applying this metric, the authors concluded that paralogous genes within the
      mouse genome or the human genome are more functionally similar on average than
      orthologous genes between these genomes, an unexpected result with broad
      implications if true. We suggest, based on both theoretical and empirical
      considerations, that this proposed metric should not be interpreted as a
      functional similarity, and therefore cannot be used to support any conclusions
      about the "ortholog conjecture" (or, more properly, the "ortholog functional
      conservation hypothesis"). First, we reexamine the case studies presented by
      Nehrt et al. as examples of orthologs with divergent functions, and come to a
      very different conclusion: they actually exemplify how GO annotations for
      orthologous genes provide complementary information about conserved biological
      functions. We then show that there is a global ascertainment bias in the
      experiment-based GO annotations for human and mouse genes: particular types of
      experiments tend to be performed in different model organisms. We conclude that
      the reported statistical differences in annotations between pairs of orthologous
      genes do not reflect differences in biological function, but rather
      complementarity in experimental approaches. Our results underscore two general
      considerations for researchers proposing novel types of analysis based on the GO:
      1) that GO annotations are often incomplete, potentially in a biased manner, and
      subject to an "open world assumption" (absence of an annotation does not imply
      absence of a function), and 2) that conclusions drawn from a novel, large-scale
      GO analysis should whenever possible be supported by careful, in-depth
      examination of examples, to help ensure the conclusions have a justifiable
      biological basis.

PMID- 22359496
TI  - Noise and robustness in phyllotaxis.
AB  - A striking feature of vascular plants is the regular arrangement of lateral
      organs on the stem, known as phyllotaxis. The most common phyllotactic patterns
      can be described using spirals, numbers from the Fibonacci sequence and the
      golden angle. This rich mathematical structure, along with the experimental
      reproduction of phyllotactic spirals in physical systems, has led to a view of
      phyllotaxis focusing on regularity. However all organisms are affected by natural
      stochastic variability, raising questions about the effect of this variability on
      phyllotaxis and the achievement of such regular patterns. Here we address these
      questions theoretically using a dynamical system of interacting sources of
      inhibitory field. Previous work has shown that phyllotaxis can emerge
      deterministically from the self-organization of such sources and that inhibition
      is primarily mediated by the depletion of the plant hormone auxin through
      polarized transport. We incorporated stochasticity in the model and found three
      main classes of defects in spiral phyllotaxis--the reversal of the handedness of
      spirals, the concomitant initiation of organs and the occurrence of distichous
      angles--and we investigated whether a secondary inhibitory field filters out
      defects. Our results are consistent with available experimental data and yield a
      prediction of the main source of stochasticity during organogenesis. Our model
      can be related to cellular parameters and thus provides a framework for the
      analysis of phyllotactic mutants at both cellular and tissular levels. We propose
      that secondary fields associated with organogenesis, such as other biochemical
      signals or mechanical forces, are important for the robustness of phyllotaxis.
      More generally, our work sheds light on how a target pattern can be achieved
      within a noisy background.

PMID- 22359497
TI  - The role of conserved waters in conformational transitions of Q61H K-ras.
AB  - To investigate the stability and functional role of long-residence water
      molecules in the Q61H variant of the signaling protein K-ras, we analyzed all
      available Ras crystal structures and conformers derived from a series of
      independent explicit solvent molecular dynamics (MD) simulations totaling 1.76
      us. We show that the protein samples a different region of phase space in the
      presence and absence of several crystallographically conserved and buried water
      molecules. The dynamics of these waters is coupled with the local as well as the
      global motions of the protein, in contrast to less buried waters whose exchange
      with bulk is only loosely coupled with the motion of loops in their vicinity.
      Aided by two novel reaction coordinates involving the distance (d) between the
      C(alpha) atoms of G60 at switch 2 and G10 at the P-loop and the N-C(alpha)-C-O
      dihedral (xi) of G60, we further show that three water molecules located in
      lobe1, at the interface between the lobes and at lobe2, are involved in the
      relative motion of residues at the two lobes of Q61H K-ras. Moreover, a d/xi plot
      classifies the available Ras x-ray structures and MD-derived K-ras conformers
      into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free
      conformational states. The population of these states and the transition between
      them is modulated by water-mediated correlated motions involving the functionally
      critical switch 2, P-loop and helix 3. These results suggest that water molecules
      act as allosteric ligands to induce a population shift among distinct switch 2
      conformations that differ in effector recognition.

PMID- 22359498
TI  - Five questions about viral trafficking in neurons.

PMID- 22359499
TI  - Mycobacterium tuberculosis ClpP1 and ClpP2 function together in protein
      degradation and are required for viability in vitro and during infection.
AB  - In most bacteria, Clp protease is a conserved, non-essential serine protease that
      regulates the response to various stresses. Mycobacteria, including Mycobacterium
      tuberculosis (Mtb) and Mycobacterium smegmatis, unlike most well studied
      prokaryotes, encode two ClpP homologs, ClpP1 and ClpP2, in a single operon. Here
      we demonstrate that the two proteins form a mixed complex (ClpP1P2) in
      mycobacteria. Using two different approaches, promoter replacement, and a novel
      system of inducible protein degradation, leading to inducible expression of clpP1
      and clpP2, we demonstrate that both genes are essential for growth and that a
      marked depletion of either one results in rapid bacterial death. ClpP1P2 protease
      appears important in degrading missense and prematurely terminated peptides, as
      partial depletion of ClpP2 reduced growth specifically in the presence of
      antibiotics that increase errors in translation. We further show that the ClpP1P2
      protease is required for the degradation of proteins tagged with the SsrA motif,
      a tag co-translationally added to incomplete protein products. Using active site
      mutants of ClpP1 and ClpP2, we show that the activity of each subunit is required
      for proteolysis, for normal growth of Mtb in vitro and during infection of mice.
      These observations suggest that the Clp protease plays an unusual and essential
      role in Mtb and may serve as an ideal target for antimycobacterial therapy.

PMID- 22359500
TI  - Mechanisms of pathogenesis, infective dose and virulence in human parasites.
AB  - The number of pathogens that are required to infect a host, termed infective
      dose, varies dramatically across pathogen species. It has recently been predicted
      that infective dose will depend upon the mode of action of the molecules that
      pathogens use to facilitate their infection. Specifically, pathogens which use
      locally acting molecules will require a lower infective dose than pathogens that
      use distantly acting molecules. Furthermore, it has also been predicted that
      pathogens with distantly acting immune modulators may be more virulent because
      they have a large number of cells in the inoculums, which will cause more harm to
      host cells. We formally test these predictions for the first time using data on
      43 different human pathogens from a range of taxonomic groups with diverse life
      histories. We found that pathogens using local action do have lower infective
      doses, but are not less virulent than those using distant action. Instead, we
      found that virulence was negatively correlated with infective dose, and higher in
      pathogens infecting wounded skin, compared with those ingested or inhaled. More
      generally, our results show that broad-scale comparative analyses can explain
      variation in parasite traits such as infective dose and virulence, whilst
      highlighting the importance of mechanistic details.

PMID- 22359502
TI  - Portrait of Candida albicans adherence regulators.
AB  - Cell-substrate adherence is a fundamental property of microorganisms that enables
      them to exist in biofilms. Our study focuses on adherence of the fungal pathogen
      Candida albicans to one substrate, silicone, that is relevant to device
      associated infection. We conducted a mutant screen with a quantitative flow-cell
      assay to identify thirty transcription factors that are required for adherence.
      We then combined nanoString gene expression profiling with functional analysis to
      elucidate relationships among these transcription factors, with two major goals:
      to extend our understanding of transcription factors previously known to govern
      adherence or biofilm formation, and to gain insight into the many transcription
      factors we identified that were relatively uncharacterized, particularly in the
      context of adherence or cell surface biogenesis. With regard to the first goal,
      we have discovered a role for biofilm regulator Bcr1 in adherence, and found that
      biofilm regulator Ace2 is a major functional target of chromatin remodeling
      factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a
      new connection between them. With regard to the second goal, our findings reveal
      existence of a large regulatory network that connects eleven adherence
      regulators, the zinc-response regulator Zap1, and approximately one quarter of
      the predicted cell surface protein genes in this organism. This limited yet
      sensitive glimpse of mutant gene expression changes had thus defined one of the
      broadest cell surface regulatory networks in C. albicans.

PMID- 22359501
TI  - Concerted actions of a thermo-labile regulator and a unique intergenic RNA
      thermosensor control Yersinia virulence.
AB  - Expression of all Yersinia pathogenicity factors encoded on the virulence
      plasmid, including the yop effector and the ysc type III secretion genes, is
      controlled by the transcriptional activator LcrF in response to temperature.
      Here, we show that a protein- and RNA-dependent hierarchy of thermosensors induce
      LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is
      modest and mediated by the thermo-sensitive modulator YmoA, which represses
      transcription from a single promoter located far upstream of the yscW-lcrF operon
      at moderate temperatures. The transcriptional response is complemented by a
      second layer of temperature-control induced by a unique cis-acting RNA element
      located within the intergenic region of the yscW-lcrF transcript. Structure
      probing demonstrated that this region forms a secondary structure composed of two
      stemloops at 25 degrees C. The second hairpin sequesters the lcrF ribosomal
      binding site by a stretch of four uracils. Opening of this structure was favored
      at 37 degrees C and permitted ribosome binding at host body temperature. Our
      study further provides experimental evidence for the biological relevance of an
      RNA thermometer in an animal model. Following oral infections in mice, we found
      that two different Y. pseudotuberculosis patient isolates expressing a stabilized
      thermometer variant were strongly reduced in their ability to disseminate into
      the Peyer's patches, liver and spleen and have fully lost their lethality.
      Intriguingly, Yersinia strains with a destabilized version of the thermosensor
      were attenuated or exhibited a similar, but not a higher mortality. This
      illustrates that the RNA thermometer is the decisive control element providing
      just the appropriate amounts of LcrF protein for optimal infection efficiency.

PMID- 22359503
TI  - Behavioral and immune responses to infection require Galphaq- RhoA signaling in
      C. elegans.
AB  - Following pathogen infection the hosts' nervous and immune systems react with
      coordinated responses to the danger. A key question is how the neuronal and
      immune responses to pathogens are coordinated, are there common signaling
      pathways used by both responses? Using C. elegans we show that infection by
      pathogenic strains of M. nematophilum, but not exposure to avirulent strains,
      triggers behavioral and immune responses both of which require a conserved
      Galphaq-RhoGEF Trio-Rho signaling pathway. Upon infection signaling by the
      Galphaq pathway within cholinergic motorneurons is necessary and sufficient to
      increase release of the neurotransmitter acetylcholine and increase locomotion
      rates and these behavioral changes result in C. elegans leaving lawns of M.
      nematophilum. In the immune response to infection signaling by the Galphaq
      pathway within rectal epithelial cells is necessary and sufficient to cause
      changes in cell morphology resulting in tail swelling that limits the infection.
      These Galphaq mediated behavioral and immune responses to infection are separate,
      act in a cell autonomous fashion and activation of this pathway in the
      appropriate cells can trigger these responses in the absence of infection. Within
      the rectal epithelium the Galphaq signaling pathway cooperates with a Ras
      signaling pathway to activate a Raf-ERK-MAPK pathway to trigger the cell
      morphology changes, whereas in motorneurons Galphaq signaling triggers behavioral
      responses independent of Ras signaling. Thus, a conserved Galphaq pathway
      cooperates with cell specific factors in the nervous and immune systems to
      produce appropriate responses to pathogen. Thus, our data suggests that ligands
      for Gq coupled receptors are likely to be part of the signals generated in
      response to M. nematophilum infection.

PMID- 22359504
TI  - Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination
      within the vector during tick-to-mammal transmission.
AB  - While the roles of rpoS(Bb) and RpoS-dependent genes have been studied
      extensively within the mammal, the contribution of the RpoS regulon to the tick
      phase of the Borrelia burgdorferi enzootic cycle has not been examined. Herein,
      we demonstrate that RpoS-dependent gene expression is prerequisite for the
      transmission of spirochetes by feeding nymphs. RpoS-deficient organisms are
      confined to the midgut lumen where they transform into an unusual morphotype
      (round bodies) during the later stages of the blood meal. We show that round body
      formation is rapidly reversible, and in vitro appears to be attributable, in
      part, to reduced levels of Coenzyme A disulfide reductase, which among other
      functions, provides NAD+ for glycolysis. Our data suggest that spirochetes
      default to an RpoS-independent program for round body formation upon sensing that
      the energetics for transmission are unfavorable.

PMID- 22359505
TI  - FOXO3 regulates CD8 T cell memory by T cell-intrinsic mechanisms.
AB  - CD8 T cell responses have three phases: expansion, contraction, and memory.
      Dynamic alterations in proliferation and apoptotic rates control CD8 T cell
      numbers at each phase, which in turn dictate the magnitude of CD8 T cell memory.
      Identification of signaling pathways that control CD8 T cell memory is
      incomplete. The PI3K/Akt signaling pathway controls cell growth in many cell
      types by modulating the activity of FOXO transcription factors. But the role of
      FOXOs in regulating CD8 T cell memory remains unknown. We show that
      phosphorylation of Akt, FOXO and mTOR in CD8 T cells occurs in a dynamic fashion
      in vivo during an acute viral infection. To elucidate the potentially dynamic
      role for FOXO3 in regulating homeostasis of activated CD8 T cells in lymphoid and
      non-lymphoid organs, we infected global and T cell-specific FOXO3-deficient mice
      with Lymphocytic Choriomeningitis Virus (LCMV). We found that FOXO3 deficiency
      induced a marked increase in the expansion of effector CD8 T cells,
      preferentially in the spleen, by T cell-intrinsic mechanisms. Mechanistically,
      the enhanced accumulation of proliferating CD8 T cells in FOXO3-deficient mice
      was not attributed to an augmented rate of cell division, but instead was linked
      to a reduction in cellular apoptosis. These data suggested that FOXO3 might
      inhibit accumulation of growth factor-deprived proliferating CD8 T cells by
      reducing their viability. By virtue of greater accumulation of memory precursor
      effector cells during expansion, the numbers of memory CD8 T cells were
      strikingly increased in the spleens of both global and T cell-specific FOXO3
      deficient mice. The augmented CD8 T cell memory was durable, and FOXO3 deficiency
      did not perturb any of the qualitative attributes of memory T cells. In summary,
      we have identified FOXO3 as a critical regulator of CD8 T cell memory, and
      therapeutic modulation of FOXO3 might enhance vaccine-induced protective immunity
      against intracellular pathogens.

PMID- 22359506
TI  - Introgression of ivermectin resistance genes into a susceptible Haemonchus
      contortus strain by multiple backcrossing.
AB  - Anthelmintic drug resistance in livestock parasites is already widespread and in
      recent years there has been an increasing level of anthelmintic drug selection
      pressure applied to parasitic nematode populations in humans leading to concerns
      regarding the emergence of resistance. However, most parasitic nematodes,
      particularly those of humans, are difficult experimental subjects making
      mechanistic studies of drug resistance extremely difficult. The small ruminant
      parasitic nematode Haemonchus contortus is a more amenable model system to study
      many aspects of parasite biology and investigate the basic mechanisms and
      genetics of anthelmintic drug resistance. Here we report the successful
      introgression of ivermectin resistance genes from two independent ivermectin
      resistant strains, MHco4(WRS) and MHco10(CAVR), into the susceptible genome
      reference strain MHco3(ISE) using a backcrossing approach. A panel of
      microsatellite markers were used to monitor the procedure. We demonstrated that
      after four rounds of backcrossing, worms that were phenotypically resistant to
      ivermectin had a similar genetic background to the susceptible reference strain
      based on the bulk genotyping with 18 microsatellite loci and individual
      genotyping with a sub-panel of 9 microsatellite loci. In addition, a single
      marker, Hcms8a20, showed evidence of genetic linkage to an ivermectin resistance
      conferring locus providing a starting point for more detailed studies of this
      genomic region to identify the causal mutation(s). This work presents a novel
      genetic approach to study anthelmintic resistance and provides a "proof-of
      concept" of the use of forward genetics in an important model strongylid parasite
      of relevance to human hookworms. The resulting strains provide valuable resources
      for candidate gene studies, whole genome approaches and for further genetic
      analysis to identify ivermectin resistance loci.

PMID- 22359507
TI  - Efficient capture of infected neutrophils by dendritic cells in the skin inhibits
      the early anti-leishmania response.
AB  - Neutrophils and dendritic cells (DCs) converge at localized sites of acute
      inflammation in the skin following pathogen deposition by the bites of arthropod
      vectors or by needle injection. Prior studies in mice have shown that neutrophils
      are the predominant recruited and infected cells during the earliest stage of
      Leishmania major infection in the skin, and that neutrophil depletion promotes
      host resistance to sand fly transmitted infection. How the massive influx of
      neutrophils aimed at wound repair and sterilization might modulate the function
      of DCs in the skin has not been previously addressed. The infected neutrophils
      recovered from the skin expressed elevated apoptotic markers compared to
      uninfected neutrophils, and were preferentially captured by dermal DCs when
      injected back into the mouse ear dermis. Following challenge with L. major
      directly, the majority of the infected DCs recovered from the skin at 24 hr
      stained positive for neutrophil markers, indicating that they acquired their
      parasites via uptake of infected neutrophils. When infected, dermal DCs were
      recovered from neutrophil depleted mice, their expression of activation markers
      was markedly enhanced, as was their capacity to present Leishmania antigens ex
      vivo. Neutrophil depletion also enhanced the priming of L. major specific CD4(+)
      T cells in vivo. The findings suggest that following their rapid uptake by
      neutrophils in the skin, L. major exploits the immunosuppressive effects
      associated with the apoptotic cell clearance function of DCs to inhibit the
      development of acquired resistance until the acute neutrophilic response is
      resolved.

PMID- 22359508
TI  - A Co-Opted DEAD-Box RNA helicase enhances tombusvirus plus-strand synthesis.
AB  - Replication of plus-strand RNA viruses depends on recruited host factors that aid
      several critical steps during replication. In this paper, we show that an
      essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly
      affects replication of Tomato bushy stunt virus (TBSV). To separate the role of
      Ded1p in viral protein translation from its putative replication function, we
      utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro
      data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral
      replicase. We also find that Ded1p is a component of the tombusvirus replicase
      complex and Ded1p binds to the 3'-end of the viral minus-stranded RNA. The data
      obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p
      unwinds local structures at the 3'-end of the TBSV (-)RNA, rendering the RNA
      compatible for initiation of (+)-strand synthesis. Interestingly, we find that
      Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host
      factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis.
      Altogether, the two host factors enhance TBSV replication synergistically by
      interacting with the viral (-)RNA and the replication proteins. In addition, we
      have developed an in vitro assay for Flock house virus (FHV), a small RNA virus
      of insects, that also demonstrated positive effect on FHV replicase activity by
      the added Ded1p helicase. Thus, two small RNA viruses, which do not code for
      their own helicases, seems to recruit a host RNA helicase to aid their
      replication in infected cells.

PMID- 22359509
TI  - Plasmacytoid dendritic cells sequester high prion titres at early stages of prion
      infection.
AB  - In most transmissible spongiform encephalopathies prions accumulate in the
      lymphoreticular system (LRS) long before they are detectable in the central
      nervous system. While a considerable body of evidence showed that B lymphocytes
      and follicular dendritic cells play a major role in prion colonization of
      lymphoid organs, the contribution of various other cell types, including antigen
      presenting cells, to the accumulation and the spread of prions in the LRS are not
      well understood. A comprehensive study to compare prion titers of candidate cell
      types has not been performed to date, mainly due to limitations in the scope of
      animal bioassays where prohibitively large numbers of mice would be required to
      obtain sufficiently accurate data. By taking advantage of quantitative in vitro
      prion determination and magnetic-activated cell sorting, we studied the kinetics
      of prion accumulation in various splenic cell types at early stages of prion
      infection. Robust estimates for infectious titers were obtained by statistical
      modelling using a generalized linear model. Whilst prions were detectable in B
      and T lymphocytes and in antigen-presenting cells like dendritic cells and
      macrophages, highest infectious titers were determined in two cell types that
      have previously not been associated with prion pathogenesis, plasmacytoid
      dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK
      cells were more than twice, and pDCs about seven-fold, as infectious as
      lymphocytes respectively. This result was unexpected since, in accordance to
      previous reports prion protein, an obligate requirement for prion replication,
      was undetectable in pDCs. This underscores the importance of prion sequestration
      and dissemination by antigen-presenting cells which are among the first cells of
      the immune system to encounter pathogens. We furthermore report the first
      evidence for a release of prions from lymphocytes and DCs of scrapie-infected
      mice ex vivo, a process that is associated with a release of exosome-like
      membrane vesicles.

PMID- 22359510
TI  - Positive selection for new disease mutations in the human germline: evidence from
      the heritable cancer syndrome multiple endocrine neoplasia type 2B.
AB  - Multiple endocrine neoplasia type 2B (MEN2B) is a highly aggressive thyroid
      cancer syndrome. Since almost all sporadic cases are caused by the same
      nucleotide substitution in the RET proto-oncogene, the calculated disease
      incidence is 100-200 times greater than would be expected based on the genome
      average mutation frequency. In order to determine whether this increased
      incidence is due to an elevated mutation rate at this position (true mutation hot
      spot) or a selective advantage conferred on mutated spermatogonial stem cells, we
      studied the spatial distribution of the mutation in 14 human testes. In donors
      aged 36-68, mutations were clustered with small regions of each testis having
      mutation frequencies several orders of magnitude greater than the rest of the
      testis. In donors aged 19-23 mutations were almost non-existent, demonstrating
      that clusters in middle-aged donors grew during adulthood. Computational analysis
      showed that germline selection is the only plausible explanation. Testes of men
      aged 75-80 were heterogeneous with some like middle-aged and others like younger
      testes. Incorporating data on age-dependent death of spermatogonial stem cells
      explains the results from all age groups. Germline selection also explains
      MEN2B's male mutation bias and paternal age effect. Our discovery focuses
      attention on MEN2B as a model for understanding the genetic and biochemical basis
      of germline selection. Since RET function in mouse spermatogonial stem cells has
      been extensively studied, we are able to suggest that the MEN2B mutation provides
      a selective advantage by altering the PI3K/AKT and SFK signaling pathways.
      Mutations that are preferred in the germline but reduce the fitness of offspring
      increase the population's mutational load. Our approach is useful for studying
      other disease mutations with similar characteristics and could uncover additional
      germline selection pathways or identify true mutation hot spots.

PMID- 22359511
TI  - Genomic restructuring in the Tasmanian devil facial tumour: chromosome painting
      and gene mapping provide clues to evolution of a transmissible tumour.
AB  - Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that
      threatens the world's largest marsupial carnivore, the Tasmanian devil, with
      extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild
      devil numbers, and intense research efforts to understand and contain the disease
      have since demonstrated that the tumour is a clonal cell line transmitted by
      allograft. We used chromosome painting and gene mapping to deconstruct the DFTD
      karyotype and determine the chromosome and gene rearrangements involved in
      carcinogenesis. Chromosome painting on three different DFTD tumour strains
      determined the origins of marker chromosomes and provided a general overview of
      the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence
      in situ hybridisation provided a finer level of resolution of genome
      rearrangements in DFTD strains. Our findings demonstrate that only limited
      regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD.
      Regions rearranged in DFTD are also highly rearranged between different
      marsupials. Differences between strains are limited, reflecting the unusually
      stable nature of DFTD. Finally, our detailed maps of both the devil and tumour
      karyotypes provide a physical framework for future genomic investigations into
      DFTD.

PMID- 22359513
TI  - Computational prediction and molecular characterization of an oomycete effector
      and the cognate Arabidopsis resistance gene.
AB  - Hyaloperonospora arabidopsidis (Hpa) is an obligate biotroph oomycete pathogen of
      the model plant Arabidopsis thaliana and contains a large set of effector
      proteins that are translocated to the host to exert virulence functions or
      trigger immune responses. These effectors are characterized by conserved amino
      terminal translocation sequences and highly divergent carboxyl-terminal
      functional domains. The availability of the Hpa genome sequence allowed the
      computational prediction of effectors and the development of effector delivery
      systems enabled validation of the predicted effectors in Arabidopsis. In this
      study, we identified a novel effector ATR39-1 by computational methods, which was
      found to trigger a resistance response in the Arabidopsis ecotype Weiningen (Wei
      0). The allelic variant of this effector, ATR39-2, is not recognized, and two
      amino acid residues were identified and shown to be critical for this loss of
      recognition. The resistance protein responsible for recognition of the ATR39-1
      effector in Arabidopsis is RPP39 and was identified by map-based cloning. RPP39
      is a member of the CC-NBS-LRR family of resistance proteins and requires the
      signaling gene NDR1 for full activity. Recognition of ATR39-1 in Wei-0 does not
      inhibit growth of Hpa strains expressing the effector, suggesting complex
      mechanisms of pathogen evasion of recognition, and is similar to what has been
      shown in several other cases of plant-oomycete interactions. Identification of
      this resistance gene/effector pair adds to our knowledge of plant resistance
      mechanisms and provides the basis for further functional analyses.

PMID- 22359514
TI  - A strong deletion bias in nonallelic gene conversion.
AB  - Gene conversion is the unidirectional transfer of genetic information between
      orthologous (allelic) or paralogous (nonallelic) genomic segments. Though a
      number of studies have examined nucleotide replacements, little is known about
      length difference mutations produced by gene conversion. Here, we investigate
      insertions and deletions produced by nonallelic gene conversion in 338 Drosophila
      and 10,149 primate paralogs. Using a direct phylogenetic approach, we identify
      179 insertions and 614 deletions in Drosophila paralogs, and 132 insertions and
      455 deletions in primate paralogs. Thus, nonallelic gene conversion is strongly
      deletion-biased in both lineages, with almost 3.5 times as many conversion
      induced deletions as insertions. In primates, the deletion bias is considerably
      stronger for long indels and, in both lineages, the per-site rate of gene
      conversion is orders of magnitudes higher than that of ordinary mutation. Due to
      this high rate, deletion-biased nonallelic gene conversion plays a key role in
      genome size evolution, leading to the cooperative shrinkage and eventual
      disappearance of selectively neutral paralogs.

PMID- 22359516
TI  - Discovery of a modified tetrapolar sexual cycle in Cryptococcus amylolentus and
      the evolution of MAT in the Cryptococcus species complex.
AB  - Sexual reproduction in fungi is governed by a specialized genomic region called
      the mating-type locus (MAT). The human fungal pathogenic and basidiomycetous
      yeast Cryptococcus neoformans has evolved a bipolar mating system (a, alpha) in
      which the MAT locus is unusually large (>100 kb) and encodes >20 genes including
      homeodomain (HD) and pheromone/receptor (P/R) genes. To understand how this
      unique bipolar mating system evolved, we investigated MAT in the closely related
      species Tsuchiyaea wingfieldii and Cryptococcus amylolentus and discovered two
      physically unlinked loci encoding the HD and P/R genes. Interestingly, the HD (B)
      locus sex-specific region is restricted (~2 kb) and encodes two linked and
      divergently oriented homeodomain genes in contrast to the solo HD genes
      (SXI1alpha, SXI2a) of C. neoformans and Cryptococcus gattii. The P/R (A) locus
      contains the pheromone and pheromone receptor genes but has expanded considerably
      compared to other outgroup species (Cryptococcus heveanensis) and is linked to
      many of the genes also found in the MAT locus of the pathogenic Cryptococcus
      species. Our discovery of a heterothallic sexual cycle for C. amylolentus allowed
      us to establish the biological roles of the sex-determining regions. Matings
      between two strains of opposite mating-types (A1B1*A2B2) produced dikaryotic
      hyphae with fused clamp connections, basidia, and basidiospores. Genotyping
      progeny using markers linked and unlinked to MAT revealed that meiosis and
      uniparental mitochondrial inheritance occur during the sexual cycle of C.
      amylolentus. The sexual cycle is tetrapolar and produces fertile progeny of four
      mating-types (A1B1, A1B2, A2B1, and A2B2), but a high proportion of progeny are
      infertile, and fertility is biased towards one parental mating-type (A1B1). Our
      studies reveal insights into the plasticity and transitions in both mechanisms of
      sex determination (bipolar versus tetrapolar) and sexual reproduction
      (outcrossing versus inbreeding) with implications for similar evolutionary
      transitions and processes in fungi, plants, and animals.

PMID- 22359515
TI  - Repression of a potassium channel by nuclear hormone receptor and TGF-beta
      signaling modulates insulin signaling in Caenorhabditis elegans.
AB  - Transforming growth factor beta (TGF-beta) signaling acts through Smad proteins
      to play fundamental roles in cell proliferation, differentiation, apoptosis, and
      metabolism. The Receptor associated Smads (R-Smads) interact with DNA and other
      nuclear proteins to regulate target gene transcription. Here, we demonstrate that
      the Caenorhabditis elegans R-Smad DAF-8 partners with the nuclear hormone
      receptor NHR-69, a C. elegans ortholog of mammalian hepatocyte nuclear factor
      4alpha HNF4alpha), to repress the exp-2 potassium channel gene and increase
      insulin secretion. We find that NHR-69 associates with DAF-8 both in vivo and in
      vitro. Functionally, daf-8 nhr-69 double mutants show defects in neuropeptide
      secretion and phenotypes consistent with reduced insulin signaling such as
      increased expression of the sod-3 and gst-10 genes and a longer life span.
      Expression of the exp-2 gene, encoding a voltage-gated potassium channel, is
      synergistically increased in daf-8 nhr-69 mutants compared to single mutants and
      wild-type worms. In turn, exp-2 acts selectively in the ASI neurons to repress
      the secretion of the insulin-like peptide DAF-28. Importantly, exp-2 mutation
      shortens the long life span of daf-8 nhr-69 double mutants, demonstrating that
      exp-2 is required downstream of DAF-8 and NHR-69. Finally, animals over
      expressing NHR-69 specifically in DAF-28-secreting ASI neurons exhibit a
      lethargic, hypoglycemic phenotype that is rescued by exogenous glucose. We
      propose a model whereby DAF-8/R-Smad and NHR-69 negatively regulate the
      transcription of exp-2 to promote neuronal DAF-28 secretion, thus demonstrating a
      physiological crosstalk between TGF-beta and HNF4alpha-like signaling in C.
      elegans. NHR-69 and DAF-8 dependent regulation of exp-2 and DAF-28 also provides
      a novel molecular mechanism that contributes to the previously recognized link
      between insulin and TGF-beta signaling in C. elegans.

PMID- 22359517
TI  - The origin and nature of tightly clustered BTG1 deletions in precursor B-cell
      acute lymphoblastic leukemia support a model of multiclonal evolution.
AB  - Recurrent submicroscopic deletions in genes affecting key cellular pathways are a
      hallmark of pediatric acute lymphoblastic leukemia (ALL). To gain more insight
      into the mechanism underlying these deletions, we have studied the occurrence and
      nature of abnormalities in one of these genes, the B-cell translocation gene 1
      (BTG1), in a large cohort of pediatric ALL cases. BTG1 was found to be
      exclusively affected by genomic deletions, which were detected in 65 out of 722 B
      cell precursor ALL (BCP-ALL) patient samples (9%), but not in 109 T-ALL cases.
      Eight different deletion sizes were identified, which all clustered at the
      telomeric site in a hotspot region within the second (and last) exon of the BTG1
      gene, resulting in the expression of truncated BTG1 read-through transcripts. The
      presence of V(D)J recombination signal sequences at both sites of virtually all
      deletions strongly suggests illegitimate RAG1/RAG2-mediated recombination as the
      responsible mechanism. Moreover, high levels of histone H3 lysine 4
      trimethylation (H3K4me3), which is known to tether the RAG enzyme complex to DNA,
      were found within the BTG1 gene body in BCP-ALL cells, but not T-ALL cells. BTG1
      deletions were rarely found in hyperdiploid BCP-ALLs, but were predominant in
      other cytogenetic subgroups, including the ETV6-RUNX1 and BCR-ABL1 positive BCP
      ALL subgroups. Through sensitive PCR-based screening, we identified multiple
      additional BTG1 deletions at the subclonal level in BCP-ALL, with equal
      cytogenetic distribution which, in some cases, grew out into the major clone at
      relapse. Taken together, our results indicate that BTG1 deletions may act as
      "drivers" of leukemogenesis in specific BCP-ALL subgroups, in which they can
      arise independently in multiple subclones at sites that are prone to aberrant
      RAG1/RAG2-mediated recombination events. These findings provide further evidence
      for a complex and multiclonal evolution of ALL.

PMID- 22359518
TI  - The retrohoming of linear group II intron RNAs in Drosophila melanogaster occurs
      by both DNA ligase 4-dependent and -independent mechanisms.
AB  - Mobile group II introns are bacterial retrotransposons that are thought to have
      invaded early eukaryotes and evolved into introns and retroelements in higher
      organisms. In bacteria, group II introns typically retrohome via full reverse
      splicing of an excised intron lariat RNA into a DNA site, where it is reverse
      transcribed by the intron-encoded protein. Recently, we showed that linear group
      II intron RNAs, which can result from hydrolytic splicing or debranching of
      lariat RNAs, can retrohome in eukaryotes by performing only the first step of
      reverse splicing, ligating their 3' end to the downstream DNA exon. Reverse
      transcription then yields an intron cDNA, whose free end is linked to the
      upstream DNA exon by an error-prone process that yields junctions similar to
      those formed by non-homologous end joining (NHEJ). Here, by using Drosophila
      melanogaster NHEJ mutants, we show that linear intron RNA retrohoming occurs by
      major Lig4-dependent and minor Lig4-independent mechanisms, which appear to be
      related to classical and alternate NHEJ, respectively. The DNA repair polymerase
      theta plays a crucial role in both pathways. Surprisingly, however, mutations in
      Ku70, which functions in capping chromosome ends during NHEJ, have only moderate,
      possibly indirect effects, suggesting that both Lig4 and the alternate end
      joining ligase act in some retrohoming events independently of Ku. Another
      potential Lig4-independent mechanism, reverse transcriptase template switching
      from the intron RNA to the upstream exon DNA, occurs in vitro, but gives
      junctions differing from the majority in vivo. Our results show that group II
      introns can utilize cellular NHEJ enzymes for retromobility in higher organisms,
      possibly exploiting mechanisms that contribute to retrotransposition and mitigate
      DNA damage by resident retrotransposons. Additionally, our results reveal novel
      activities of group II intron reverse transcriptases, with implications for
      retrohoming mechanisms and potential biotechnological applications.

PMID- 22359519
TI  - Upsetting the dogma: germline selection in human males.

PMID- 22359520
TI  - What part of the total care consumed by type 2 diabetes patients is directly
      related to diabetes? Implications for disease management programs.
AB  - BACKGROUND: Disease management programs (DMP) aim at improving coordination and
      quality of care and reducing healthcare costs for specific chronic diseases. This
      paper investigates to what extent total healthcare utilization of type 2 diabetes
      patients is actually related to diabetes and its implications for diabetes
      management programs. RESEARCH DESIGN AND METHODS: Healthcare utilization for
      diabetes patients was analyzed using 2008 self-reported data (n=316) and data
      from electronic medical records (EMR) (n=9023), and divided whether or not care
      was described in the Dutch type 2 diabetes multidisciplinary healthcare standard.
      RESULTS: On average 4.3 different disciplines of healthcare providers were
      involved in the care for diabetes patients. Ninety-six percent contacted a GP
      practice and 63% an ophthalmologist, 24% an internist, 32% a physiotherapist and
      23% a dietician. Diabetes patients had on average 9.3 contacts with GP-practice
      of which 53% were included in the healthcare standard. Only a limited part of
      total healthcare utilization of diabetes patients was included in the healthcare
      standard and therefore theoretically included in DMPs. CONCLUSION: Organizing the
      care for diabetics in a DMP might harm the coordination and quality of all
      healthcare for diabetics. DMPs should be integrated in the overall organization
      of care.

PMID- 22359522
TI  - Reviewing the evidence on case management: lessons for successful implementation.

PMID- 22359521
TI  - Impact on continuity of care of decentralized versus partly centralized mental
      health care in Northern Norway.
AB  - BACKGROUND: The issue of continuity of care is central in contemporary
      psychiatric services research. In Norway, inpatient admissions are mainly to take
      place locally, in a system of small bed-units that represent an alternative to
      traditional central psychiatric hospitals. This type of organization may be
      advantageous for accessibility and cooperation, but has been given little
      scientific attention. AIMS: To study whether inpatients' utilization of
      outpatient services differ between an area with a decentralized care model in
      comparison to an adjacent area with a partly centralized model. METHOD: The study
      was based on data from a one-year registered prevalence sample, drawing on
      routinely sampled data supplemented with data from medical records. Service
      utilization for 247 inpatients was analyzed. The results were controlled for
      diagnosis, demographic variables, type of service system, localization of
      inpatient admissions, and length of hospitalization. RESULTS: Most inpatients in
      the area with the decentralized care model also utilized outpatient
      consultations, whereas a considerable number of inpatients in the area with a
      partly centralized model did not enter outpatient care at all. Type of service
      system, localization of inpatient admission, and length of hospitalization
      predicted inpatients' utilization of outpatient consultations. The results are
      discussed in the light of systems integration, particularly management
      arrangements and clinical bridging over the transitional phase from inpatient to
      outpatient care. CONCLUSION: Inpatients' utilization of outpatient services
      differed between an area with a decentralized care model in comparison to an
      adjacent area with a partly centralized care model. In the areas studied,
      extensive decentralization of the psychiatric services positively affected
      coordination of inpatient and outpatient services for people with severe
      psychiatric disorders. Small, local-bed units may therefore represent a
      favourable alternative to traditional central psychiatric hospitals.

PMID- 22359512
TI  - Genome-wide association study identifies novel loci associated with circulating
      phospho- and sphingolipid concentrations.
AB  - Phospho- and sphingolipids are crucial cellular and intracellular compounds.
      These lipids are required for active transport, a number of enzymatic processes,
      membrane formation, and cell signalling. Disruption of their metabolism leads to
      several diseases, with diverse neurological, psychiatric, and metabolic
      consequences. A large number of phospholipid and sphingolipid species can be
      detected and measured in human plasma. We conducted a meta-analysis of five
      European family-based genome-wide association studies (N = 4034) on plasma levels
      of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20
      lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE
      based plasmalogens (PLPE), as well as their proportions in each major class. This
      effort yielded 25 genome-wide significant loci for phospholipids (smallest P
      value = 9.88*10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10*10(
      57)). After a correction for multiple comparisons (P-value<2.2*10(-9)), we
      observed four novel loci significantly associated with phospholipids (PAQR9,
      AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up
      to 3.1% of the variance. Further analysis of the top findings with respect to
      within class molar proportions uncovered three additional loci for phospholipids
      (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid
      elongation/saturation processes or fatty acid specific turnover mechanisms. Among
      those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2,
      CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid
      and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1,
      APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses,
      associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and
      type 2 diabetes, and APOA1 and coronary artery disease were observed. In
      conclusion, our study identified nine novel phospho- and sphingolipid loci,
      substantially increasing our knowledge of the genetic basis for these traits.

PMID- 22359523
TI  - An overview of the national immunization policy making process: the role of the
      Korea expert committee on immunization practices.
AB  - The need for evidence-based decision making in immunization programs has
      increased due to the presence of multiple health priorities, limited human
      resources, expensive vaccines, and limited funds. Countries should establish a
      group of national experts to advise their Ministries of Health. So far, many
      nations have formed their own National Immunization Technical Advisory Groups
      (NITAGs). In the Republic of Korea, the Korea Expert Committee on Immunization
      Practices (KECIP), established by law in the early 1990s, has made many important
      technical recommendations to contribute to the decline in vaccine preventable
      diseases and currently functions as a NITAG. It includes 13 core members and 2
      non-core members, including a chairperson. Core members usually come from
      affiliated organizations in internal medicine, pediatrics, obstetrics,
      microbiology, preventive medicine, nursing and a representative from a consumer
      group, all of whom serve two year terms. Non-core members comprise two government
      officials belonging to the Korea Centers for Disease Control and Prevention
      (KCDC) and the Korea Food and Drug Administration. Meetings are held as needed,
      but at least twice a year, and sub-committees are formed as a resource for
      gathering, analyzing, and preparing information for the KECIP meetings. Once the
      sub-committees or the KCDC review the available data, the KECIP members discuss
      each issue in depth and develop recommendations, usually by a consensus in the
      meeting. The KECIP publishes national guidelines and immunization schedules that
      are updated regularly. KECIP's role is essentially consultative and the
      implementation of their recommendations may depend on the budget or current laws.

PMID- 22359524
TI  - The genes associated with gonadotropin-releasing hormone-dependent precocious
      puberty.
AB  - Human puberty is a complex, coordinated biological process with multiple levels
      of regulations. The timing of puberty varies greatly in children and is
      influenced by both environmental and genetic factors. The key genes of pubertal
      onset, KISS1, GPR54, GNRH1 and GNRHR, may be major causal factors underlying
      gonadotropin-releasing hormone-dependent precocious puberty (GDPP). Two gain-of
      function mutations in KISS1 and GPR54 have been identified recently as genetic
      causes of GDPP. GNRH1 and GNRHR are also gene candidates for GDPP; however no
      mutations have been identified in these genes. Presently potential genetic causes
      like LIN28B continues to appear; many areas of research await exploration in this
      context. In this review, I focus primarily on the genetic causes of GDPP.

PMID- 22359525
TI  - Comparison of the accuracy of neutrophil CD64 and C-reactive protein as a single
      test for the early detection of neonatal sepsis.
AB  - PURPOSE: Early identification of neonatal sepsis is a global issue because of
      limitations in diagnostic procedures. The objective of this study was to compare
      the diagnostic accuracy of neutrophil CD64 and C-reactive protein (CRP) as a
      single test for the early detection of neonatal sepsis. METHODS: A prospective
      study enrolled newborns with documented sepsis (n=11), clinical sepsis (n=12) and
      control newborns (n=14). CRP, neutrophil CD64, complete blood counts and blood
      culture were taken at the time of the suspected sepsis for the documented or
      clinical group and at the time of venipuncture for laboratory tests in control
      newborns. Neutrophil CD64 was analyzed by flow cytometry. RESULTS: CD64 was
      significantly elevated in the groups with documented or clinical sepsis, whereas
      CRP was not significantly increased compared with controls. For documented
      sepsis, CD64 and CRP had a sensitivity of 91% and 9%, a specificity of 83% and
      83%, a positive predictive value of 83% and 33% and a negative predictive value
      of 91% and 50%, respectively, with a cutoff value of 3.0 mg/dL for CD64 and 1.0
      mg/dL for CRP. The area under the receiver-operating characteristic curves for
      CD64 index and CRP were 0.955 and 0.527 (P<0.01), respectively. CONCLUSION: These
      preliminary data show that diagnostic accuracy of CD64 is superior to CRP when
      measured at the time of suspected sepsis, which implies that CD64 is a more
      reliable marker for the early identification of neonatal sepsis as a single
      determination compared with CRP.

PMID- 22359526
TI  - Transforming growth factor beta receptor II polymorphisms are associated with
      Kawasaki disease.
AB  - PURPOSE: Transforming growth factor beta receptor 2 (TGFBR2) is a tumor
      suppressor gene that plays a role in the differentiation of striated cells and
      remodeling of coronary arteries. Single nucleotide polymorphisms (SNPs) of this
      gene are associated with Marfan syndrome and sudden death in patients with
      coronary artery disease. Cardiovascular remodeling and T cell activation of
      TGFBR2 gene suggest that the TGFBR2 gene SNPs are related to the pathogenesis of
      Kawasaki disease (KD) and coronary artery lesion (CAL). METHODS: The subjects
      were 105 patients with KD and 500 healthy adults as controls. Mean age of KD
      group was 32 months age and 26.6% of those had CAL. We selected TGFBR2 gene SNPs
      from serum and performed direct sequencing. RESULTS: The sequences of the eleven
      SNPs in the TGFBR2 gene were compared between the KD group and controls. Three
      SNPs (rs1495592, rs6550004, rs795430) were associated with development of KD
      (P=0.019, P=0.026, P=0.016, respectively). One SNP (rs1495592) was associated
      with CAL in KD group (P=0.022). CONCLUSION: Eleven SNPs in TGFBR2 gene were
      identified at that time the genome wide association. But, with the change of the
      data base, only six SNPs remained associated with the TGFBR2 gene. One of the six
      SNPs (rs6550004) was associated with development of KD. One SNP associated with
      CAL (rs1495592) was disassociated from the TGFBR2 gene. The other five SNPs were
      not functionally identified, but these SNPs are notable because the data base is
      changing. Further studies involving larger group of patients with KD are needed.

PMID- 22359527
TI  - Partial anomalous pulmonary venous connection with intact atrial septum in a
      child with ventricular septal defect: a case report.
AB  - Partial anomalous pulmonary vein connection (PAPVC) is a rare congenital abnormal
      cardiac defect involving the pulmonary veins draining into the right atrium (RA)
      directly or indirectly by venous connection. Ninety percent of PAPVCs are
      accompanied by atrial septal defect (ASD). To our knowledge, there is no previous
      report of PAPVC with ventricular septal defect (VSD) without ASD in Korea, and in
      this paper, we report the first such case. A 2-day-old girl was admitted into the
      Chonnam National University Hospital for evaluation of a cardiac murmur. An
      echocardiogram revealed perimembranous VSD without ASD. She underwent patch
      closure of the VSD at 5 months of age. Although the VSD was completely closed,
      she had persistent cardiomegaly with right ventricular volume overload, as
      revealed by echocardiography. Three years later, cardiac catheterization and
      chest computed tomography revealed a PAPVC, with the right upper pulmonary vein
      draining into the right SVC. Therefore, correction of the PAPVC was surgically
      performed at 3 years of age. We conclude that it is important to suspect PAPVC in
      patients with right ventricular volume overload, but without ASD.

PMID- 22359528
TI  - PHACE association with intracranial, oropharyngeal hemangiomas, and an atypical
      patent ductus arteriosus arising from the tortuous left subclavian artery in a
      premature infant.
AB  - PHACE association is a rare neurocutaneous condition in which facial hemangiomas
      associate with a spectrum of posterior fossa malformations, arterial
      cerebrovascular anomalies, cardiovascular anomalies, and eye anomalies. We
      reported a case of PHACE association in a premature infant showing facial,
      intracranial, and oropharyngeal hemangiomas with evidence of the Dandy-Walker
      variant and complicated cardiovascular anomalies, including a right-sided aortic
      arch and an atypical patent ductus arteriosus arising from a tortuous left
      subclavian artery. To our knowledge, intracranial hemangiomas are rare in PHACE
      association, and a concomitant oropharyngeal hemangioma has not been previously
      reported in the PHACE association literature. In infants presenting with large,
      plaque-like facial hemangiomas, it is important to conduct active cardiovascular
      and neurological evaluations. Special attention should be given to the
      laryngoscopic examination to search for additional hemangiomas in the airway.

PMID- 22359529
TI  - A 40-50kDa Glycoprotein Associated with Mucus is Identified as alpha-1-Acid
      Glycoprotein in Carcinoma of the Stomach.
AB  - BACKGROUND AND AIM: Secreted gastric mucins are large O-glycosylated proteins of
      crude mucus gels which are aberrantly expressed in malignancy. An albumin
      associated 55-65kDa glycoprotein was previously shown in mucus gels in gastric
      cancer. The aim of this study was to investigate its expression and
      identification in human gastric tissue. METHODS: Mucins were purified from crude
      mucus scrapings of 16 partial and 11 total resections and a rabbit polyclonal
      antibody was raised to the 55-65kDa glycoprotein. The location and expression of
      the glycoprotein was examined in normal gastric mucosa (n=20), intestinal
      metaplasia (n=18) and gastric cancer (n=27) tissue by immunohistochemistry.
      Mucins were analyzed by isoelectric focusing (IEF) on 2-D polyacrylamide gels.
      Identification of the 40-50kDa glycoprotein was by MALDI-TOF MS technique. Plasma
      levels were examined by Western blotting. RESULTS: Extensive SDS-PAGE analysis
      gave a PAS positive glycoprotein in the 40-50kDa range, in patients with gastric
      cancer but not normals. It was expressed in parietal and columnar cells of normal
      gastric tissue and intestinal metaplasia respectively, and in 22 of 27 gastric
      cancer specimens. In 2-D PAGE stained with Coomassie Blue there were 3 spots
      positively identified as alpha-1-acid glycoprotein (AGP) by MALDI-TOF MS
      technique. PAS staining revealed a single bright spot in the same position but
      could not be identified. Preliminary measurements showed slightly higher levels
      of AGP in plasma of patients with gastric carcinoma. CONCLUSION: AGP levels are
      increased in gastric tissue and in the plasma of those with carcinoma of the
      stomach.

PMID- 22359530
TI  - A quick, cost-free method of purification of DNA fragments from agarose gel.
AB  - In this short communication we report a quick, cost-free method of purification
      of DNA fragments from agarose gel. Unlike those procedures that involve
      commercial kits, this method uses glass wool or absorbent cotton to filter
      agarose gel during a quick spinning-down of DNA, thus significantly simplifying
      the routine practice of many molecular biologists and decreasing the cost.

PMID- 22359531
TI  - Prostatic metastasis of pulmonary large cell neuroendocrine carcinoma.
AB  - Lung cancer metastases to the prostate are uncommon, and are usually found
      incidentally during autopsy. This case report describes a 77-year-old man with a
      large cell neuroendocrine carcinoma (LCNEC) of the lung and metastases from this
      primary cancer in the prostate. During the follow-up after the chemotherapy
      performed for pulmonary LCNEC, pelvic computed tomography revealed a prostatic
      tumor and prostatic needle biopsy was performed. Histologically, the tumor was
      identified as LCNEC, forming a tissue architecture closely resembling the
      previously diagnosed lung cancer. The tumor cells were immunohistochemically
      positive for thyroid transcription factor-1. These findings led to a diagnosis of
      prostatic metastasis of pulmonary LCNEC.

PMID- 22359534
TI  - Comparison of marine spatial planning methods in Madagascar demonstrates value of
      alternative approaches.
AB  - The Government of Madagascar plans to increase marine protected area coverage by
      over one million hectares. To assist this process, we compare four methods for
      marine spatial planning of Madagascar's west coast. Input data for each method
      was drawn from the same variables: fishing pressure, exposure to climate change,
      and biodiversity (habitats, species distributions, biological richness, and
      biodiversity value). The first method compares visual color classifications of
      primary variables, the second uses binary combinations of these variables to
      produce a categorical classification of management actions, the third is a target
      based optimization using Marxan, and the fourth is conservation ranking with
      Zonation. We present results from each method, and compare the latter three
      approaches for spatial coverage, biodiversity representation, fishing cost and
      persistence probability. All results included large areas in the north, central,
      and southern parts of western Madagascar. Achieving 30% representation targets
      with Marxan required twice the fish catch loss than the categorical method. The
      categorical classification and Zonation do not consider targets for conservation
      features. However, when we reduced Marxan targets to 16.3%, matching the
      representation level of the "strict protection" class of the categorical result,
      the methods show similar catch losses. The management category portfolio has
      complete coverage, and presents several management recommendations including
      strict protection. Zonation produces rapid conservation rankings across large,
      diverse datasets. Marxan is useful for identifying strict protected areas that
      meet representation targets, and minimize exposure probabilities for conservation
      features at low economic cost. We show that methods based on Zonation and a
      simple combination of variables can produce results comparable to Marxan for
      species representation and catch losses, demonstrating the value of comparing
      alternative approaches during initial stages of the planning process. Choosing an
      appropriate approach ultimately depends on scientific and political factors
      including representation targets, likelihood of adoption, and persistence goals.

PMID- 22359533
TI  - Decoding the distribution of glycan receptors for human-adapted influenza A
      viruses in ferret respiratory tract.
AB  - Ferrets are widely used as animal models for studying influenza A viral
      pathogenesis and transmissibility. Human-adapted influenza A viruses primarily
      target the upper respiratory tract in humans (infection of the lower respiratory
      tract is observed less frequently), while in ferrets, upon intranasal inoculation
      both upper and lower respiratory tract are targeted. Viral tropism is governed by
      distribution of complex sialylated glycan receptors in various cells/tissues of
      the host that are specifically recognized by influenza A virus hemagglutinin
      (HA), a glycoprotein on viral surface. It is generally known that upper
      respiratory tract of humans and ferrets predominantly express alpha2->6
      sialylated glycan receptors. However much less is known about the fine structure
      of these glycan receptors and their distribution in different regions of the
      ferret respiratory tract. In this study, we characterize distribution of glycan
      receptors going beyond terminal sialic acid linkage in the cranial and caudal
      regions of the ferret trachea (upper respiratory tract) and lung hilar region
      (lower respiratory tract) by multiplexing use of various plant lectins and human
      adapted HAs to stain these tissue sections. Our findings show that the sialylated
      glycan receptors recognized by human-adapted HAs are predominantly distributed in
      submucosal gland of lung hilar region as a part of O-linked glycans. Our study
      has implications in understanding influenza A viral pathogenesis in ferrets and
      also in employing ferrets as animal models for developing therapeutic strategies
      against influenza.

PMID- 22359532
TI  - Serum vitamin D levels are not predictive of the progression of chronic liver
      disease in hepatitis C patients with advanced fibrosis.
AB  - In animal models and human cross-sectional studies, vitamin D deficiency has been
      associated with liver disease progression. Vitamin D supplementation has been
      suggested as a treatment to prevent disease progression. We sought to evaluate
      the role of vitamin D levels in predicting chronic liver disease development. We
      conducted a nested case-control study of vitamin D levels in subjects with
      (cases) and without (controls) liver histologic progression or clinical
      decompensation over the course of the HALT-C Trial. Vitamin D levels were
      measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were
      included. No difference in baseline vitamin D levels were found between cases and
      controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in
      cases and controls over time (P = 0.0005), however, there was no difference in
      the level of decline (P = 0.37). Among study subjects with diabetes mellitius,
      baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3
      ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black
      case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08)
      No difference in vitamin D levels was found between patients with and without
      progression of hepatitis C-associated liver disease over 4 years. Our data do not
      suggest any role for vitamin D supplementation in patients with advanced chronic
      hepatitis C and raise the possibility that higher vitamin D levels may be
      associated with disease progression.

PMID- 22359535
TI  - Large-scale model-based assessment of deer-vehicle collision risk.
AB  - Ungulates, in particular the Central European roe deer Capreolus capreolus and
      the North American white-tailed deer Odocoileus virginianus, are economically and
      ecologically important. The two species are risk factors for deer-vehicle
      collisions and as browsers of palatable trees have implications for forest
      regeneration. However, no large-scale management systems for ungulates have been
      implemented, mainly because of the high efforts and costs associated with
      attempts to estimate population sizes of free-living ungulates living in a
      complex landscape. Attempts to directly estimate population sizes of deer are
      problematic owing to poor data quality and lack of spatial representation on
      larger scales. We used data on >74,000 deer-vehicle collisions observed in 2006
      and 2009 in Bavaria, Germany, to model the local risk of deer-vehicle collisions
      and to investigate the relationship between deer-vehicle collisions and both
      environmental conditions and browsing intensities. An innovative modelling
      approach for the number of deer-vehicle collisions, which allows nonlinear
      environment-deer relationships and assessment of spatial heterogeneity, was the
      basis for estimating the local risk of collisions for specific road types on the
      scale of Bavarian municipalities. Based on this risk model, we propose a new
      "deer-vehicle collision index" for deer management. We show that the risk of deer
      vehicle collisions is positively correlated to browsing intensity and to harvest
      numbers. Overall, our results demonstrate that the number of deer-vehicle
      collisions can be predicted with high precision on the scale of municipalities.
      In the densely populated and intensively used landscapes of Central Europe and
      North America, a model-based risk assessment for deer-vehicle collisions provides
      a cost-efficient instrument for deer management on the landscape scale. The
      measures derived from our model provide valuable information for planning road
      protection and defining hunting quota. Open-source software implementing the
      model can be used to transfer our modelling approach to wildlife-vehicle
      collisions elsewhere.

PMID- 22359537
TI  - Circulating and PBMC Lp-PLA2 associate differently with oxidative stress and
      subclinical inflammation in nonobese women (menopausal status).
AB  - BACKGROUND: This study aimed to determine the association of lipoprotein
      associated phospholipase A(2) (Lp-PLA(2)) activity in circulation and peripheral
      blood mononuclear cells (PBMCs) with inflammatory and oxidative stress markers in
      nonobese women and according to menopausal status. Lp-PLA(2) activity, a marker
      for cardiovascular risk is associated with inflammation and oxidative stress.
      METHODOLOGY/PRINCIPAL FINDINGS: Eighty postmenopausal women (53.0+/-4.05 yr) and
      96 premenopausal women (39.7+/-9.25 yr) participated in this study. Lp-PLA(2)
      activities, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta
      in plasma as well as in PBMCs were measured. Plasma ox-LDL was also measured.
      Postmenopausal women demonstrated higher circulating levels of ox-LDL and IL-6,
      as well as IL-6, TNF-alpha, and IL-1beta in PBMCs, than premenopausal women. In
      both groups, plasma Lp-PLA(2) activity positively correlated with Lp-PLA(2)
      activity in PBMCs and plasma ox-LDL. In premenopausal women, Lp-PLA(2) activities
      in plasma and PBMCs positively correlated with IL-6, TNF-alpha, and IL-1beta in
      PBMCs. In postmenopausal women, plasma ox-LDL positively correlated with PBMC
      cytokine production. In subgroup analysis of postmenopausal women according to
      plasma ox-LDL level (median level: 48.715 U/L), a significant increase in Lp
      PLA(2) activity in the plasma but not the PBMCs was found in the high ox-LDL
      subgroup. Plasma Lp-PLA(2) activity positively correlated with unstimulated PBMC
      Lp-PLA(2) activity in the low ox-LDL subgroup (r = 0.627, P<0.001), whereas in
      the high ox-LDL circulating Lp-PLA(2) activity positively correlated with plasma
      ox-LDL (r = 0.390, P = 0.014) but not with Lp-PLA(2) activity in PBMCs.
      CONCLUSIONS/SIGNIFICANCE: The lack of relation between circulating Lp-PLA(2)
      activity and Lp-PLA(2) activity in PBMCs was found in postmenopausal women with
      high ox-LDL. This may indicate other sources of circulating Lp-PLA(2) activity
      except PBMC in postmenopausal women with high ox-LDL. We also demonstrated that
      circulating Lp-PLA(2) and PBMC secreted Lp-PLA(2) associate differently with
      markers of oxidative stress and sub clinical inflammation in nonobese women,
      particularly according to the menopausal states.

PMID- 22359538
TI  - Rheotaxis in larval zebrafish is mediated by lateral line mechanosensory hair
      cells.
AB  - The lateral line sensory system, found in fish and amphibians, is used in prey
      detection, predator avoidance and schooling behavior. This system includes cell
      clusters, called superficial neuromasts, located on the surface of head and trunk
      of developing larvae. Mechanosensory hair cells in the center of each neuromast
      respond to disturbances in the water and convey information to the brain via the
      lateral line ganglia. The convenient location of mechanosensory hair cells on the
      body surface has made the lateral line a valuable system in which to study hair
      cell damage and regeneration. One way to measure hair cell survival and recovery
      is to assay behaviors that depend on their function. We built a system in which
      orientation against constant water flow, positive rheotaxis, can be
      quantitatively assessed. We found that zebrafish larvae perform positive
      rheotaxis and that, similar to adult fish, larvae use both visual and lateral
      line input to perform this behavior. Disruption or damage of hair cells in the
      absence of vision leads to a marked decrease in rheotaxis that recovers upon hair
      cell repair or regeneration.

PMID- 22359536
TI  - Characterization of a large group of individuals with huntington disease and
      their relatives enrolled in the COHORT study.
AB  - BACKGROUND: Careful characterization of the phenotype and genotype of Huntington
      disease (HD) can foster better understanding of the condition. METHODS: We
      conducted a cohort study in the United States, Canada, and Australia of members
      of families affected by HD. We collected demographic and clinical data, conducted
      the Unified Huntington's Disease Rating Scale and Mini-Mental State Examination,
      and determined Huntingtin trinucleotide CAG repeat length. We report primarily on
      cross-sectional baseline data from this recently completed prospective,
      longitudinal, observational study. RESULTS: As of December 31, 2009, 2,318
      individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis
      groups. Three groups had expanded CAG alleles (36 repeats or more): individuals
      with clinically diagnosed HD [n = 930], and clinically unaffected first-degree
      relatives who had previously pursued [n = 248] or not pursued [n = 112]
      predictive DNA testing. Three groups lacked expanded alleles: first-degree
      relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic
      testing, and spouses and caregivers [n = 430]. Baseline mean performance differed
      across groups in all motor, behavioral, cognitive, and functional measures
      (p<0.001). Clinically unaffected individuals with expanded alleles weighed less
      (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the
      Mini Mental State Examination; p = 0.008) than individuals without expanded
      alleles. The frequency of "high normal" repeat lengths (27 to 35) was 2.5% and
      repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.
      CONCLUSION: Baseline analysis of COHORT study participants revealed differences
      that emerge prior to clinical diagnosis. Longitudinal investigation of this
      cohort will further characterize the natural history of HD and genetic and
      biological modifiers. TRIAL REGISTRATION: Clinicaltrials.gov NCT00313495.

PMID- 22359539
TI  - Functional characterization of cultured keratinocytes after acute cutaneous burn
      injury.
AB  - BACKGROUND: In addition to forming the epithelial barrier against the outside
      environment keratinocytes are immunologically active cells. In the treatment of
      severely burned skin, cryoconserved keratinocyte allografts gain in importance.
      It has been proposed that these allografts accelerate wound healing also due to
      the expression of a favourable--keratinocyte-derived--cytokine and growth factor
      milieu. METHODS: In this study the morphology and cytokine expression profile of
      keratinocytes from skin after acute burn injury was compared to non-burned skin.
      Skin samples were obtained from patients after severe burn injury and healthy
      controls. Cells were cultured and secretion of selected inflammatory mediators
      was quantified using Bioplex Immunoassays. Immunohistochemistry was performed to
      analyse further functional and morphologic parameters. RESULTS: Histology
      revealed increased terminal differentiation of keratinocytes (CK10, CK11) in
      allografts from non-burned skin compared to a higher portion of proliferative
      cells (CK5, vimentin) in acute burn injury. Increased levels of IL-1alpha, IL-2,
      IL-4, IL-10, IFN-gamma and TNFalpha could be detected in culture media of burn
      injury skin cultures. Both culture groups contained large amounts of IL-1RA. IL-6
      and GM-CSF were increased during the first 15 days of culture of burned skin
      compared to control skin. Levels of VEGF, FGF-basic, TGF-beta und G-CSF were high
      in both but not significantly different. Cryoconservation led to a diminished
      mediator synthesis except for higher levels of intracellular IL-1alpha and IL
      1beta. CONCLUSION: Skin allografts from non-burned skin show a different
      secretion pattern of keratinocyte-derived cytokines and inflammatory mediators
      compared to keratinocytes after burn injury. As these secreted molecules exert
      auto- and paracrine effects and subsequently contribute to healing and barrier
      restoration after acute burn injury therapies affecting this specific
      cytokine/growth factor micromilieu could be beneficial in burned patients.

PMID- 22359541
TI  - Fungal melanins differ in planar stacking distances.
AB  - Melanins are notoriously difficult to study because they are amorphous, insoluble
      and often associated with other biological materials. Consequently, there is a
      dearth of structural techniques to study this enigmatic pigment. Current models
      of melanin structure envision the stacking of planar structures. X ray
      diffraction has historically been used to deduce stacking parameters. In this
      study we used X ray diffraction to analyze melanins derived from Cryptococcus
      neoformans, Aspergillus niger, Wangiella dermatitides and Coprinus comatus.
      Analysis of melanin in melanized C. neoformans encapsulated cells was precluded
      by the fortuitous finding that the capsular polysaccharide had a diffraction
      spectrum that was similar to that of isolated melanin. The capsular
      polysaccharide spectrum was dominated by a broad non-Bragg feature consistent
      with origin from a repeating structural motif that may arise from inter-molecular
      interactions and/or possibly gel organization. Hence, we isolated melanin from
      each fungal species and compared diffraction parameters. The results show that
      the inferred stacking distances of fungal melanins differ from that reported for
      synthetic melanin and neuromelanin, occupying intermediate position between these
      other melanins. These results suggest that all melanins have a fundamental
      diffracting unit composed of planar graphitic assemblies that can differ in
      stacking distance. The stacking peak appears to be a distinguishing universal
      feature of melanins that may be of use in characterizing these enigmatic
      pigments.

PMID- 22359540
TI  - Structural organization of DNA in chlorella viruses.
AB  - Chlorella viruses have icosahedral capsids with an internal membrane enclosing
      their large dsDNA genomes and associated proteins. Their genomes are packaged in
      the particles with a predicted DNA density of ca. 0.2 bp nm(-3). Occasionally
      infection of an algal cell by an individual particle fails and the viral DNA is
      dynamically ejected from the capsid. This shows that the release of the DNA
      generates a force, which can aid in the transfer of the genome into the host in a
      successful infection. Imaging of ejected viral DNA indicates that it is
      intimately associated with proteins in a periodic fashion. The bulk of the
      protein particles detected by atomic force microscopy have a size of ~60 kDa and
      two proteins (A278L and A282L) of about this size are among 6 basic putative DNA
      binding proteins found in a proteomic analysis of DNA binding proteins packaged
      in the virion. A combination of fluorescence images of ejected DNA and a
      bioinformatics analysis of the DNA reveal periodic patterns in the viral DNA. The
      periodic distribution of GC rich regions in the genome provides potential binding
      sites for basic proteins. This DNA/protein aggregation could be responsible for
      the periodic concentration of fluorescently labeled DNA observed in ejected viral
      DNA. Collectively the data indicate that the large chlorella viruses have a DNA
      packaging strategy that differs from bacteriophages; it involves proteins and
      share similarities to that of chromatin structure in eukaryotes.

PMID- 22359542
TI  - Protein kinase C iota regulates pancreatic acinar-to-ductal metaplasia.
AB  - Pancreatic acinar-to-ductal metaplasia (ADM) is associated with an increased risk
      of pancreatic cancer and is considered a precursor of pancreatic ductal
      adenocarcinoma. Transgenic expression of transforming growth factor alpha (TGF
      alpha) or K-ras(G12D) in mouse pancreatic epithelium induces ADM in vivo. Protein
      kinase C iota (PKCiota) is highly expressed in human pancreatic cancer and is
      required for the transformed growth and tumorigenesis of pancreatic cancer cells.
      In this study, PKCiota expression was assessed in a mouse model of K-ras(G12D)
      induced pancreatic ADM and pancreatic cancer. The ability of K-ras(G12D) to
      induce pancreatic ADM in explant culture, and the requirement for PKCiota, was
      investigated. PKCiota is elevated in human and mouse pancreatic ADM and
      intraepithelial neoplastic lesions in vivo. We demonstrate that K-ras(G12D) is
      sufficient to induce pancreatic ADM in explant culture, exhibiting many of the
      same morphologic and biochemical alterations observed in TGF-alpha-induced ADM,
      including a dependence on Notch activation. PKCiota is highly expressed in both
      TGF-alpha- and K-ras(G12D)-induced pancreatic ADM and inhibition of PKCiota
      significantly reduces TGF-alpha- and K-ras(G12D)-mediated ADM. Inhibition of
      PKCiota suppresses K-ras(G12D)-induced MMP-7 expression and Notch activation, and
      exogenous MMP-7 restores K-ras(G12D)-mediated ADM in PKCiota-depleted cells,
      implicating a K-ras(G12D)-PKCiota-MMP-7 signaling axis that likely induces ADM
      through Notch activation. Our results indicate that PKCiota is an early marker of
      pancreatic neoplasia and suggest that PKCiota is a potential downstream target of
      K-ras(G12D) in pancreatic ductal metaplasia in vivo.

PMID- 22359543
TI  - Improved control of tuberculosis and activation of macrophages in mice lacking
      protein kinase R.
AB  - Host factors that microbial pathogens exploit for their propagation are potential
      targets for therapeuic countermeasures. No host enzyme has been identified whose
      genetic absence benefits the intact mammalian host in vivo during infection with
      Mycobacterium tuberculosis (Mtb), the leading cause of death from bacterial
      infection. Here, we report that the dsRNA-dependent protein kinase (PKR) is such
      an enzyme. PKR-deficient mice contained fewer viable Mtb and showed less
      pulmonary pathology than wild type mice. We identified two potential mechanisms
      for the protective effect of PKR deficiency: increased apoptosis of macrophages
      in response to Mtb and enhanced activation of macrophages in response to IFN
      gamma. The restraining effect of PKR on macrophage activation was explained by
      its mediation of a previously unrecognized ability of IFN-gamma to induce low
      levels of the macrophage deactivating factor interleukin 10 (IL10). These
      observations suggest that PKR inhibitors may prove useful as an adjunctive
      treatment for tuberculosis.

PMID- 22359544
TI  - Investigations on transgenerational epigenetic response down the male line in F2
      pigs.
AB  - We investigated the nutritional effects on carcass traits, gene expression and
      DNA methylation in a three generation Large White pig feeding experiment. A group
      of experimental (E) F0 boars were fed a standard diet supplemented with high
      amounts of methylating micronutrients whereas a control group (C) of F0 boars
      received a standard diet. These differentially fed F0 boars sired F1 boars which
      then sired 60 F2 pigs. Carcass traits were compared between 36 F2 descendants of
      E F0 boars and 24 F2 descendants of C F0 boars. The two F2 offspring groups
      differed with respect to backfat percentage (P = 0.03) and tended to differ with
      respect to adipose tissue (P = 0.09), fat thickness at the 10(th) rib (P = 0.08)
      and at the croup (P = 0.09) as well as percentages of shoulder (P = 0.07).
      Offspring from the experimental F0 boars had a higher percentage of shoulder and
      were leaner compared to the control group. Gene expression profiles showed
      significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2
      offspring for 79, 64 and 53 genes for muscle, liver and kidney RNA, respectively.
      We found that in liver and muscle respective pathways of lipid metabolism and
      metabolic pathway were over-represented for the differentially expressed genes
      between these groups. A DNA methylation analysis in promoters of differentially
      expressed genes indicated a significant difference in DNA methylation at the IYD
      gene. If these responses on carcass traits, gene expression and DNA methylation
      withstand verification and can indeed be attributed to transgenerational
      epigenetic inheritance, it would open up pioneering application in pork
      production and would have implications for human health.

PMID- 22359545
TI  - Protection from intracellular oxidative stress by cytoglobin in normal and
      cancerous oesophageal cells.
AB  - Cytoglobin is an intracellular globin of unknown function that is expressed
      mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin
      include buffering of intracellular oxygen and detoxification of reactive oxygen
      species. Previous work in our laboratory has demonstrated that cytoglobin affords
      protection from oxidant-induced DNA damage when over expressed in vitro, but the
      importance of this in more physiologically relevant models of disease is unknown.
      Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its
      expression is strongly down-regulated in non-cancerous oesophageal biopsies from
      patients with TOC compared with normal biopsies. Therefore, oesophageal cells
      provide an ideal experimental model to test our hypothesis that downregulation of
      cytoglobin expression sensitises cells to the damaging effects of reactive oxygen
      species, particularly oxidative DNA damage, and that this could potentially
      contribute to the TOC phenotype. In the current study, we tested this hypothesis
      by manipulating cytoglobin expression in both normal and oesophageal cancer cell
      lines, which have normal physiological and no expression of cytoglobin
      respectively. Our results show that, in agreement with previous findings, over
      expression of cytoglobin in cancer cell lines afforded protection from chemically
      induced oxidative stress but this was only observed at non-physiological
      concentrations of cytoglobin. In addition, down regulation of cytoglobin in
      normal oesophageal cells had no effect on their sensitivity to oxidative stress
      as assessed by a number of end points. We therefore conclude that normal
      physiological concentrations of cytoglobin do not offer cytoprotection from
      reactive oxygen species, at least in the current experimental model.

PMID- 22359546
TI  - Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human
      fibroblasts.
AB  - Coenzyme Q(10) (CoQ(10)) is a potent lipophilic antioxidant in cell membranes and
      a carrier of electrons in the mitochondrial respiratory chain. We previously
      characterized the effects of varying severities of CoQ(10) deficiency on ROS
      production and mitochondrial bioenergetics in cells harboring genetic defects of
      CoQ(10) biosynthesis. We observed a unimodal distribution of ROS production with
      CoQ(10) deficiency: cells with <20% of CoQ(10) and 50-70% of CoQ(10) did not
      generate excess ROS while cells with 30-45% of CoQ(10) showed increased ROS
      production and lipid peroxidation. Because our previous studies were limited to a
      small number of mutant cell lines with heterogeneous molecular defects, here, we
      treated 5 control and 2 mildly CoQ(10) deficient fibroblasts with varying doses
      of 4-nitrobenzoate (4-NB), an analog of 4-hydroxybenzoate (4-HB) and inhibitor of
      4-para-hydroxybenzoate:polyprenyl transferase (COQ2) to induce a range of CoQ(10)
      deficiencies. Our results support the concept that the degree of CoQ(10)
      deficiency in cells dictates the extent of ATP synthesis defects and ROS
      production and that 40-50% residual CoQ(10) produces maximal oxidative stress and
      cell death.

PMID- 22359547
TI  - Transcriptional profiling of disease-induced host responses in bovine
      tuberculosis and the identification of potential diagnostic biomarkers.
AB  - Bovine tuberculosis (bTb) remains a major and economically important disease of
      livestock. Improved ante-mortem diagnostic tools would help to underpin novel
      control strategies. The definition of biomarkers correlating with disease
      progression could have impact on the rational design of novel diagnostic
      approaches for bTb. We have used a murine bTb model to identify promising
      candidates in the host transcriptome post-infection. RNA from in vitro-stimulated
      splenocytes and lung cells from BALB/c mice infected aerogenically with
      Mycobacterium bovis were probed with high-density microarrays to identify
      possible biomarkers of disease. In antigen-stimulated splenocytes we found
      statistically significant differential regulation of 1109 genes early (3 days)
      after infection and 1134 at a later time-point post-infection (14 days). 618 of
      these genes were modulated at both time points. In lung cells, 282 genes were
      significantly modulated post-infection. Amongst the most strongly up-regulated
      genes were: granzyme A, granzyme B, cxcl9, interleukin-22, and ccr6. The
      expression of 14 out of the most up-regulated genes identified in the murine
      studies was evaluated using in vitro with antigen-stimulated PBMC from uninfected
      and naturally infected cattle. We show that the expression of cxcl9, cxcl10,
      granzyme A and interleukin-22 was significantly increased in PBMC from infected
      cattle compared to naive animals following PPD stimulation in vitro. Thus, murine
      transcriptome analysis can be used to predict immunological responses in cattle
      allowing the prioritisation of CXCLl9, CXCL10, Granzyme A and IL-22 as potential
      additional readout systems for the ante-mortem diagnosis of bovine tuberculosis.

PMID- 22359548
TI  - Exon-specific QTLs skew the inferred distribution of expression QTLs detected
      using gene expression array data.
AB  - Mapping of expression quantitative trait loci (eQTLs) is an important technique
      for studying how genetic variation affects gene regulation in natural
      populations. In a previous study using Illumina expression data from human
      lymphoblastoid cell lines, we reported that cis-eQTLs are especially enriched
      around transcription start sites (TSSs) and immediately upstream of transcription
      end sites (TESs). In this paper, we revisit the distribution of eQTLs using
      additional data from Affymetrix exon arrays and from RNA sequencing. We confirm
      that most eQTLs lie close to the target genes; that transcribed regions are
      generally enriched for eQTLs; that eQTLs are more abundant in exons than introns;
      and that the peak density of eQTLs occurs at the TSS. However, we find that the
      intriguing TES peak is greatly reduced or absent in the Affymetrix and RNA-seq
      data. Instead our data suggest that the TES peak observed in the Illumina data is
      mainly due to exon-specific QTLs that affect 3' untranslated regions, where most
      of the Illumina probes are positioned. Nonetheless, we do observe an overall
      enrichment of eQTLs in exons versus introns in all three data sets, consistent
      with an important role for exonic sequences in gene regulation.

PMID- 22359550
TI  - Balanced input allows optimal encoding in a stochastic binary neural network
      model: an analytical study.
AB  - Recent neurophysiological experiments have demonstrated a remarkable effect of
      attention on the underlying neural activity that suggests for the first time that
      information encoding is indeed actively influenced by attention. Single cell
      recordings show that attention reduces both the neural variability and
      correlations in the attended condition with respect to the non-attended one. This
      reduction of variability and redundancy enhances the information associated with
      the detection and further processing of the attended stimulus. Beyond the
      attentional paradigm, the local activity in a neural circuit can be modulated in
      a number of ways, leading to the general question of understanding how the
      activity of such circuits is sensitive to these relatively small modulations.
      Here, using an analytically tractable neural network model, we demonstrate how
      this enhancement of information emerges when excitatory and inhibitory synaptic
      currents are balanced. In particular, we show that the network encoding
      sensitivity--as measured by the Fisher information--is maximized at the exact
      balance. Furthermore, we find a similar result for a more realistic spiking
      neural network model. As the regime of balanced inputs has been experimentally
      observed, these results suggest that this regime is functionally important from
      an information encoding standpoint.

PMID- 22359549
TI  - Mesenchymal stem cells lack efficacy in the treatment of experimental autoimmune
      neuritis despite in vitro inhibition of T-cell proliferation.
AB  - Mesenchymal stem cells have been demonstrated to ameliorate experimental
      autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, prompting
      clinical trials in multiple sclerosis which are currently ongoing. An important
      question is whether this therapeutic effect generalises to other autoimmune
      neurological diseases. We performed two trials of efficacy of MSCs in
      experimental autoimmune neuritis (EAN) in Lewis (LEW/Han (M)Hsd) rats, a model of
      human autoimmune inflammatory neuropathies. No differences between the groups
      were found in clinical, histological or electrophysiological outcome measures.
      This was despite the ability of mesenchymal stem cells to inhibit proliferation
      of CD4+ T-cells in vitro. Therefore the efficacy of MSCs observed in autoimmune
      CNS demyelination models do not necessarily generalise to the treatment of other
      forms of neurological autoimmunity.

PMID- 22359551
TI  - Evolution of resistance to Aurora kinase B inhibitors in leukaemia cells.
AB  - Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical
      trials for the treatment of haematological and solid malignancies. However,
      knowledge of the molecular factors that influence sensitivity and resistance
      remains limited. Herein, we developed and characterised an in vitro leukaemia
      model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute
      lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 uM
      ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA
      damaging agents, but were hypersensitive to an Aurora kinase A inhibitor.
      Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a
      G160E amino acid substitution. Molecular modelling of drug binding in Aurora B
      containing this mutation suggested that resistance is mediated by the glutamate
      substitution preventing formation of an active drug-binding motif. Progression of
      resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived
      sequentially from CEM/AKB4 in 8 and 16 uM ZM447439 respectively, was mediated by
      additional defects. These defects were independent of Aurora B and multi-drug
      resistance pathways and are associated with reduced apoptosis mostly likely due
      to reduced inhibition of the catalytic activity of aurora kinase B in the
      presence of drug. Our findings are important in the context of the use of these
      new targeted agents in treatment regimes against leukaemia and suggest resistance
      to therapy may arise through multiple independent mechanisms.

PMID- 22359552
TI  - Small fragment homologous replacement: evaluation of factors influencing
      modification efficiency in an eukaryotic assay system.
AB  - Homologous Replacement is used to modify specific gene sequences of chromosomal
      DNA in a process referred to as "Small Fragment Homologous Replacement", where
      DNA fragments replace genomic target resulting in specific sequence changes. To
      optimize the efficiency of this process, we developed a reporter based assay
      system where the replacement frequency is quantified by cytofluorimetric analysis
      following restoration of a stably integrated mutated eGFP gene in the genome of
      SV-40 immortalized mouse embryonic fibroblasts (MEF-SV-40). To obtain the highest
      correction frequency with this system, several parameters were considered:
      fragment synthesis and concentration, cell cycle phase and methylation status of
      both fragment and recipient genome. In addition, different drugs were employed to
      test their ability to improve technique efficiency. SFHR-mediated genomic
      modification resulted to be stably transmitted for several cell generations and
      confirmed at transcript and genomic levels. Modification efficiency was estimated
      in a range of 0.01-0.5%, further increasing when PARP-1 repair pathway was
      inhibited. In this study, for the first time SFHR efficiency issue was
      systematically approached and in part addressed, therefore opening new potential
      therapeutic ex-vivo applications.

PMID- 22359553
TI  - Influence of contact definitions in assessment of the relative importance of
      social settings in disease transmission risk.
AB  - BACKGROUND: Realistic models of disease transmission incorporating complex
      population heterogeneities require input from quantitative population mixing
      studies. We use contact diaries to assess the relative importance of social
      settings in respiratory pathogen spread using three measures of person contact
      hours (PCH) as proxies for transmission risk with an aim to inform bipartite
      network models of respiratory pathogen transmission. METHODS AND FINDINGS: Our
      survey examines the contact behaviour for a convenience sample of 65 adults, with
      each encounter classified as occurring in a work, retail, home, social, travel or
      "other" setting. The diary design allows for extraction of PCH-interaction
      (cumulative time in face-face conversational or touch interaction with contacts)-
      analogous to the contact measure used in several existing surveys--as well as PCH
      setting (product of time spent in setting and number of people present) and PCH
      reach (product of time spent in setting and number of people in close proximity).
      Heterogeneities in day-dependent distribution of risk across settings are
      analysed using partitioning and cluster analyses and compared between days and
      contact measures. Although home is typically the highest-risk setting when PCH
      measures isolate two-way interactions, its relative importance compared to social
      and work settings may reduce when adopting a more inclusive contact measure that
      considers the number and duration of potential exposure events. CONCLUSIONS:
      Heterogeneities in location-dependent contact behaviour as measured by contact
      diary studies depend on the adopted contact definition. We find that contact
      measures isolating face-face conversational or touch interactions suggest that
      contact in the home dominates, whereas more inclusive contact measures indicate
      that home and work settings may be of higher importance. In the absence of
      definitive knowledge of the contact required to facilitate transmission of
      various respiratory pathogens, it is important for surveys to consider
      alternative contact measures.

PMID- 22359554
TI  - The rationality of prejudices.
AB  - We model an N-player repeated prisoner's dilemma in which players are given
      traits (e.g., height, age, wealth) which, we assume, affect their behavior. The
      relationship between traits and behavior is unknown to other players. We then
      analyze the performance of "prejudiced" strategies--strategies that draw
      inferences based on the observation of some or all of these traits, and
      extrapolate the inferred behavior to other carriers of these traits. Such
      prejudiced strategies have the advantage of learning rapidly, and hence of being
      well adapted to rapidly changing conditions that might result, for example, from
      high migration or birth rates. We find that they perform remarkably well, and
      even systematically outperform both Tit-For-Tat and ALLD when the population
      changes rapidly.

PMID- 22359555
TI  - Genome-wide association study identified a narrow chromosome 1 region associated
      with chicken growth traits.
AB  - Chicken growth traits are important economic traits in broilers. A large number
      of studies are available on finding genetic factors affecting chicken growth.
      However, most of these studies identified chromosome regions containing putative
      quantitative trait loci and finding causal mutations is still a challenge. In
      this genome-wide association study (GWAS), we identified a narrow 1.5 Mb region
      (173.5-175 Mb) of chicken (Gallus gallus) chromosome (GGA) 1 to be strongly
      associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth
      traits included aggregate body weight (BW) at 0-90 d of age measured weekly,
      biweekly average daily gains (ADG) derived from weekly body weight, and breast
      muscle weight (BMW), leg muscle weight (LMW) and wing weight (WW) at 90 d of age.
      Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant
      effects for all growth traits in this study, including a SNP at 8.9 Kb upstream
      of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for
      WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP
      in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3
      FOXO1A region contained two microRNA genes that could bind to messenger
      ribonucleic acid (mRNA) of IGF1, FOXO1A and KPNA3. It was further indicated that
      the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42
      d.

PMID- 22359556
TI  - The role of actin turnover in retrograde actin network flow in neuronal growth
      cones.
AB  - The balance of actin filament polymerization and depolymerization maintains a
      steady state network treadmill in neuronal growth cones essential for motility
      and guidance. Here we have investigated the connection between depolymerization
      and treadmilling dynamics. We show that polymerization-competent barbed ends are
      concentrated at the leading edge and depolymerization is distributed throughout
      the peripheral domain. We found a high-to-low G-actin gradient between peripheral
      and central domains. Inhibiting turnover with jasplakinolide collapsed this
      gradient and lowered leading edge barbed end density. Ultrastructural analysis
      showed dramatic reduction of leading edge actin filament density and filament
      accumulation in central regions. Live cell imaging revealed that the leading edge
      retracted even as retrograde actin flow rate decreased exponentially. Inhibition
      of myosin II activity before jasplakinolide treatment lowered baseline retrograde
      flow rates and prevented leading edge retraction. Myosin II activity
      preferentially affected filopodial bundle disassembly distinct from the global
      effects of jasplakinolide on network turnover. We propose that growth cone
      retraction following turnover inhibition resulted from the persistence of myosin
      II contractility even as leading edge assembly rates decreased. The buildup of
      actin filaments in central regions combined with monomer depletion and reduced
      polymerization from barbed ends suggests a mechanism for the observed exponential
      decay in actin retrograde flow. Our results show that growth cone motility is
      critically dependent on continuous disassembly of the peripheral actin network.

PMID- 22359557
TI  - The response of vocal fold fibroblasts and mesenchymal stromal cells to
      vibration.
AB  - Illumination of cellular changes caused by mechanical forces present within the
      laryngeal microenvironment may well guide strategies for tissue engineering the
      vocal fold lamina propria. The purpose of this study was to compare the response
      of human vocal fold fibroblasts (hVFF) and bone marrow mesenchymal stem cells (BM
      MSC) to vibratory stimulus. In order to study these effects, a bioreactor capable
      of vibrating two cell seeded substrates was developed. The cell seeded substrates
      contact each other as a result of the sinusoidal frequency, producing a motion
      similar to the movement of true vocal folds. Utilizing this bioreactor, hVFF and
      BM-MSC were subjected to 200 Hz vibration and 20% strain for 8 hours.
      Immunohistochemistry (Ki-67 and TUNEL) was performed to examine cell
      proliferation and apoptosis respectively, while semi-quantitative RT-PCR was used
      to assess extracellular matrix related gene expression. HVFF significantly
      proliferated (p = 0.011) when subjected to 200 Hz vibration and 20% strain, while
      BM-MSC did not (p = 1.0). A statistically significant increase in apoptosis of BM
      MSC (p = 0.0402) was observed under the experimental conditions; however high
      cell viability (96%) was maintained. HVFF did not have significantly altered
      apoptosis (p = 0.7849) when subjected to vibration and strain. Semi-quantitative
      RT-PCR results show no significant differences in expression levels of collagen I
      (BM-MSC p = 0.1951, hVFF p = v0.3629), fibronectin (BM-MSC p = 0.1951, hVFF p =
      0.2513), and TGF-beta1 (BM-MSC p = 0.2534, hVFF p = 0.6029) between vibratory and
      static conditions in either cell type. Finally, smooth muscle actin mRNA was not
      present in either vibrated or static samples, indicating that no myofibroblast
      differentiation occurred for either cell type. Together, these results
      demonstrate that BM-MSC may be a suitable alternative to hVFF for vocal fold
      tissue engineering. Further investigation into a larger number of gene markers,
      protein levels, increased number of donors and vibratory conditions are
      warranted.

PMID- 22359558
TI  - Activation of H+-ATPase of the plasma membrane of Saccharomyces cerevisiae by
      glucose: the role of sphingolipid and lateral enzyme mobility.
AB  - Activation of the plasma membrane H(+)-ATPase of the yeast Saccharomyces
      cerevisiae by glucose is a complex process that has not yet been completely
      elucidated. This study aimed to shed light on the role of lipids and the lateral
      mobility of the enzyme complex during its activation by glucose. The significance
      of H(+)-ATPase oligomerization for the activation of H(+)-ATPase by glucose was
      shown using the strains lcb1-100 and erg6, with the disturbed synthesis of
      sphyngolipid and ergosterol, respectively. Experiments with GFP-fused H(+)-ATPase
      showed a decrease in fluorescence anisotropy during the course of glucose
      activation, suggesting structural reorganization of the molecular domains. An
      immunogold assay showed that the incubation with glucose results in the spatial
      redistribution of ATPase complexes in the plasma membrane. The data suggest that
      (1) to be activated by glucose, H(+)-ATPase is supposed to be in an oligomeric
      state, and (2) glucose activation is accompanied by the spatial movements of H(+)
      ATPase clusters in the PM.

PMID- 22359559
TI  - Transgenic potatoes for potato cyst nematode control can replace pesticide use
      without impact on soil quality.
AB  - Current and future global crop yields depend upon soil quality to which soil
      organisms make an important contribution. The European Union seeks to protect
      European soils and their biodiversity for instance by amending its Directive on
      pesticide usage. This poses a challenge for control of Globodera pallida (a
      potato cyst nematode) for which both natural resistance and rotational control
      are inadequate. One approach of high potential is transgenically based
      resistance. This work demonstrates the potential in the field of a new transgenic
      trait for control of G. pallida that suppresses root invasion. It also
      investigates its impact and that of a second transgenic trait on the non-target
      soil nematode community. We establish that a peptide that disrupts chemoreception
      of nematodes without a lethal effect provides resistance to G. pallida in both a
      containment and a field trial when precisely targeted under control of a root tip
      specific promoter. In addition we combine DNA barcoding and quantitative PCR to
      recognise nematode genera from soil samples without microscope-based observation
      and use the method for nematode faunal analysis. This approach establishes that
      the peptide and a cysteine proteinase inhibitor that offer distinct bases for
      transgenic plant resistance to G. pallida do so without impact on the non-target
      nematode soil community.

PMID- 22359560
TI  - Characterization of the poly-T variant in the TOMM40 gene in diverse populations.
AB  - We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T,
      rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of
      Alzheimer's disease and with cognitive performance in elderly. Three allele
      groups were defined for rs10524523, hereafter '523', based on the number of 'T'
      residues: 'Short' (S, T<=19), 'Long' (L, 20<=T<=29) and 'Very Long' (VL, T>=30).
      Homopolymers, particularly long homopolymers like '523', are difficult to
      genotype because 'slippage' occurs during PCR-amplification. We initially
      genotyped this locus by PCR-amplification followed by Sanger-sequencing. However,
      we recognized the need to develop a higher-throughput genotyping method that is
      also accurate and reliable. Here we describe a new '523' genotyping assay that is
      simple and inexpensive to perform in a standard molecular genetics laboratory.
      The assay is based on the detection of differences in PCR-fragment length using
      capillary electrophoresis. We discuss technical problems, solutions, and the
      steps taken for validation. We employed the novel assay to investigate the '523'
      allele frequencies in different ethnicities. Whites and Hispanics have similar
      frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, respectively).
      In African-Americans, the frequency of the L-allele (0.10) is similar to Whites
      and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele
      is concomitantly less frequent (0.25). The allele frequencies determined using
      the new methodology are compared to previous reports for Ghanaian, Japanese,
      Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between
      TOMM40-'523' and APOE alleles. In Whites and Hispanics, consistent with previous
      reports, the L is primarily linked to epsilon4, while the majority of the VL and
      S are linked to epsilon3. Interestingly, in African-Americans, Ghanaians and
      Japanese, there is an increased frequency of the '523'S-APOEepsilon4 haplotype.
      These data may be used as references for '523' allele and '523'-APOE haplotype
      frequencies in diverse populations for the design of research studies and
      clinical trials.

PMID- 22359561
TI  - Plasma proteomic profiling in HIV-1 infected methamphetamine abusers.
AB  - We wanted to determine whether methamphetamine use affects a subset of plasma
      proteins in HIV-infected persons. Plasma samples from two visits were identified
      for subjects from four groups: HIV+, ongoing, persistent METH use; HIV+, short
      term METH abstinent; HIV+, long term METH abstinence; HIV negative, no history of
      METH use. Among 390 proteins identified, 28 showed significant changes in
      expression in the HIV+/persistent METH+ group over the two visits, which were not
      attributable to HIV itself. These proteins were involved in complement,
      coagulation pathways and oxidative stress. Continuous METH use is an unstable
      condition, altering levels of a number of plasma proteins.

PMID- 22359562
TI  - When does diversity trump ability (and vice versa) in group decision making? A
      simulation study.
AB  - It is often unclear which factor plays a more critical role in determining a
      group's performance: the diversity among members of the group or their individual
      abilities. In this study, we addressed this "diversity vs. ability" issue in a
      decision-making task. We conducted three simulation studies in which we
      manipulated agents' individual ability (or accuracy, in the context of our
      investigation) and group diversity by varying (1) the heuristics agents used to
      search task-relevant information (i.e., cues); (2) the size of their groups; (3)
      how much they had learned about a good cue search order; and (4) the magnitude of
      errors in the information they searched. In each study, we found that a
      manipulation reducing agents' individual accuracy simultaneously increased their
      group's diversity, leading to a conflict between the two. These conflicts enabled
      us to identify certain conditions under which diversity trumps individual
      accuracy, and vice versa. Specifically, we found that individual accuracy is more
      important in task environments in which cues differ greatly in the quality of
      their information, and diversity matters more when such differences are
      relatively small. Changing the size of a group and the amount of learning by an
      agent had a limited impact on this general effect of task environment.
      Furthermore, we found that a group achieves its highest accuracy when there is an
      intermediate amount of errors in the cue information, regardless of the
      environment and the heuristic used, an effect that we believe has not been
      previously reported and warrants further investigation.

PMID- 22359563
TI  - Hostility, physical aggression and trait anger as predictors for suicidal
      behavior in Chinese adolescents: a school-based study.
AB  - PURPOSE: This study explored the extent to which trait aggression is associated
      with suicidal behavior in a nationwide school-based sample of adolescents.
      METHODS: A nationwide sample of 14,537 high school students in urban areas of
      China was recruited. Information concerning suicide ideation, plans, attempts,
      trait aggression and other risk factors was collected by a self-reported
      questionnaire. Multivariate regression analyses were employed to predict suicidal
      behavior. RESULTS: Approximately 18.5% of students reported suicide ideation,
      8.7% reported suicide plans, and 4.1% reported attempts during the past one year.
      Hostility and trait anger had a significant positive association with suicidal
      ideation. Hostility and physical aggression were positively related to suicide
      plans. Hostility had a positive correlation with suicide attempts, while trait
      anger was inversely associated with suicide attempts. CONCLUSIONS: This study
      suggests that hostility, physical aggression and trait anger may be able to be
      used to predict suicidal behavior among adolescents. Suicide prevention programs
      should target at attenuating the severity of hostility, anger and physical
      aggression. But teachers and parents should also give close attention to students
      with low trait anger.

PMID- 22359564
TI  - Identification of lipases involved in PBAN stimulated pheromone production in
      Bombyx mori using the DGE and RNAi approaches.
AB  - BACKGROUND: Pheromone biosynthesis activating neuropeptide (PBAN) is a
      neurohormone that regulates sex pheromone synthesis in female moths. Bombyx mori
      is a model organism that has been used to explore the signal transduction pattern
      of PBAN, which is mediated by a G-protein coupled receptor (GPCR). Although
      significant progress has been made in elucidating PBAN-regulated lipolysis that
      releases the precursor of the sex pheromone, little is known about the molecular
      components involved in this step. To better elucidate the molecular mechanisms of
      PBAN-stimulated lipolysis of cytoplasmic lipid droplets (LDs), the associated
      lipase genes involved in PBAN- regulated sex pheromone biosynthesis were
      identified using digital gene expression (DGE) and subsequent RNA interference
      (RNAi). RESULTS: Three DGE libraries were constructed from pheromone glands (PGs)
      at different developed stages, namely, 72 hours before eclosion (-72 h), new
      emergence (0 h) and 72 h after eclosion (72 h), to investigate the gene
      expression profiles during PG development. The DGE evaluated over 5.6 million
      clean tags in each PG sample and revealed numerous genes that were differentially
      expressed at these stages. Most importantly, seven lipases were found to be
      richly expressed during the key stage of sex pheromone synthesis and release (new
      emergence). RNAi-mediated knockdown confirmed for the first time that four of
      these seven lipases play important roles in sex pheromone synthesis. CONCLUSION:
      This study has identified four lipases directly involved in PBAN-stimulated sex
      pheromone biosynthesis, which improve our understanding of the lipases involved
      in releasing bombykol precursors from triacylglycerols (TAGs) within the
      cytoplasmic LDs.

PMID- 22359566
TI  - Blood pressure modifies retinal susceptibility to intraocular pressure elevation.
AB  - Primary open angle glaucoma affects more than 67 million people. Elevated
      intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient
      availability by decreasing ocular perfusion pressure (OPP). An interaction
      between arterial blood pressure and IOP determines OPP; but the exact
      contribution that these factors have for retinal function is not fully
      understood. Here we sought to determine how acute modifications of arterial
      pressure will affect the susceptibility of neuronal function and blood flow to
      IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (~60
      mmHg, sodium nitroprusside infusion), moderate (~100 mmHg, saline), or high
      levels (~160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5-10 per
      group) were subjected to IOP challenge (10-120 mmHg, 5 mmHg steps every 3
      minutes). Electroretinograms were measured at each IOP step to assess bipolar
      cell (b-wave) and inner retinal function (scotopic threshold response or STR).
      Ocular blood flow was measured using laser-Doppler flowmetry in groups with
      similar MAP level and the same IOP challenge protocol. Both b-wave and STR
      amplitudes decreased with IOP elevation. Retinal function was less susceptible to
      IOP challenge when MAP was high, whereas the converse was true for low MAP.
      Consistent with the effects on retinal function, higher IOP was needed to
      attenuated ocular blood flow in animals with higher MAP. The susceptibility of
      retinal function to IOP challenge can be ameliorated by acute high BP, and
      exacerbated by low BP. This is partially mediated by modifications in ocular
      blood flow.

PMID- 22359567
TI  - A comprehensive overview of medical error in hospitals using incident-reporting
      systems, patient complaints and chart review of inpatient deaths.
AB  - BACKGROUND: Incident reporting systems (IRS) are used to identify medical errors
      in order to learn from mistakes and improve patient safety in hospitals. However,
      IRS contain only a small fraction of occurring incidents. A more comprehensive
      overview of medical error in hospitals may be obtained by combining information
      from multiple sources. The WHO has developed the International Classification for
      Patient Safety (ICPS) in order to enable comparison of incident reports from
      different sources and institutions. METHODS: The aim of this paper was to provide
      a more comprehensive overview of medical error in hospitals using a combination
      of different information sources. Incident reports collected from IRS, patient
      complaints and retrospective chart review in an academic acute care hospital were
      classified using the ICPS. The main outcome measures were distribution of
      incidents over the thirteen categories of the ICPS classifier "Incident type",
      described as odds ratios (OR) and proportional similarity indices (PSI). RESULTS:
      A total of 1012 incidents resulted in 1282 classified items. Large differences
      between data from IRS and patient complaints (PSI = 0.32) and from IRS and
      retrospective chart review (PSI = 0.31) were mainly attributable to behaviour (OR
      = 6.08), clinical administration (OR = 5.14), clinical process (OR = 6.73) and
      resources (OR = 2.06). CONCLUSIONS: IRS do not capture all incidents in hospitals
      and should be combined with complementary information about diagnostic error and
      delayed treatment from patient complaints and retrospective chart review. Since
      incidents that are not recorded in IRS do not lead to remedial and preventive
      action in response to IRS reports, healthcare centres that have access to
      different incident detection methods should harness information from all sources
      to improve patient safety.

PMID- 22359565
TI  - Trends in notifiable infectious diseases in China: implications for surveillance
      and population health policy.
AB  - This study aimed to analyse trends in notifiable infectious diseases in China, in
      their historical context. Both English and Chinese literature was searched and
      diseases were categorised according to the type of disease or transmission route.
      Temporal trends of morbidity and mortality rates were calculated for eight major
      infectious diseases types. Strong government commitment to public health
      responses and improvements in quality of life has led to the eradication or
      containment of a wide range of infectious diseases in China. The overall
      infectious diseases burden experienced a dramatic drop during 1975-1995, but
      since then, it reverted and maintained a gradual upward trend to date. Most
      notifiable diseases are contained at a low endemic level; however, local small
      scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re
      emerged since the 1990s and has become prevalent in the country. Sexually
      transmitted infections are in a rapid, exponential growth phase, spreading from
      core groups to the general population. Together human immunodeficiency virus
      (HIV), they account for 39% of all death cases due to infectious diseases in
      China in 2008. Zoonotic infections, such as severe acute respiratory syndrome
      (SARS), rabies and influenza, pose constant threats to Chinese residents and
      remain the most deadly disease type among the infected individuals. Therefore,
      second-generation surveillance of behavioural risks or vectors associated with
      pathogen transmission should be scaled up. It is necessary to implement public
      health interventions that target HIV and relevant coinfections, address
      transmission associated with highly mobile populations, and reduce the risk of
      cross-species transmission of zoonotic pathogens.

PMID- 22359568
TI  - Tetrahydrodipicolinate N-succinyltransferase and dihydrodipicolinate synthase
      from Pseudomonas aeruginosa: structure analysis and gene deletion.
AB  - The diaminopimelic acid pathway of lysine biosynthesis has been suggested to
      provide attractive targets for the development of novel antibacterial drugs. Here
      we report the characterization of two enzymes from this pathway in the human
      pathogen Pseudomonas aeruginosa, utilizing structural biology, biochemistry and
      genetics. We show that tetrahydrodipicolinate N-succinyltransferase (DapD) from
      P. aeruginosa is specific for the L-stereoisomer of the amino substrate L-2
      aminopimelate, and its D-enantiomer acts as a weak inhibitor. The crystal
      structures of this enzyme with L-2-aminopimelate and D-2-aminopimelate,
      respectively, reveal that both compounds bind at the same site of the enzyme.
      Comparison of the binding interactions of these ligands in the enzyme active site
      suggests misalignment of the amino group of D-2-aminopimelate for nucleophilic
      attack on the succinate moiety of the co-substrate succinyl-CoA as the structural
      basis of specificity and inhibition. P. aeruginosa mutants where the dapA gene
      had been deleted were viable and able to grow in a mouse lung infection model,
      suggesting that DapA is not an optimal target for drug development against this
      organism. Structure-based sequence alignments, based on the DapA crystal
      structure determined to 1.6 A resolution revealed the presence of two homologues,
      PA0223 and PA4188, in P. aeruginosa that could substitute for DapA in the P.
      aeruginosa PAO1DeltadapA mutant. In vitro experiments using recombinant PA0223
      protein could however not detect any DapA activity.

PMID- 22359569
TI  - Genome-wide identification, evolutionary expansion, and expression profile of
      homeodomain-leucine zipper gene family in poplar (Populus trichocarpa).
AB  - BACKGROUND: Homeodomain-leucine zipper (HD-ZIP) proteins are plant-specific
      transcriptional factors known to play crucial roles in plant development.
      Although sequence phylogeny analysis of Populus HD-ZIPs was carried out in a
      previous study, no systematic analysis incorporating genome organization, gene
      structure, and expression compendium has been conducted in model tree species
      Populus thus far. PRINCIPAL FINDINGS: In this study, a comprehensive analysis of
      Populus HD-ZIP gene family was performed. Sixty-three full-length HD-ZIP genes
      were found in Populus genome. These Populus HD-ZIP genes were phylogenetically
      clustered into four distinct subfamilies (HD-ZIP I-IV) and predominately
      distributed across 17 linkage groups (LG). Fifty genes from 25 Populus paralogous
      pairs were located in the duplicated blocks of Populus genome and then
      preferentially retained during the sequential evolutionary courses. Genomic
      organization analyses indicated that purifying selection has played a pivotal
      role in the retention and maintenance of Populus HD-ZIP gene family. Microarray
      analysis has shown that 21 Populus paralogous pairs have been differentially
      expressed across different tissues and under various stresses, with five
      paralogous pairs showing nearly identical expression patterns, 13 paralogous
      pairs being partially redundant and three paralogous pairs diversifying
      significantly. Quantitative real-time RT-PCR (qRT-PCR) analysis performed on 16
      selected Populus HD-ZIP genes in different tissues and under both drought and
      salinity stresses confirms their tissue-specific and stress-inducible expression
      patterns. CONCLUSIONS: Genomic organizations indicated that segmental
      duplications contributed significantly to the expansion of Populus HD-ZIP gene
      family. Exon/intron organization and conserved motif composition of Populus HD
      ZIPs are highly conservative in the same subfamily, suggesting the members in the
      same subfamilies may also have conservative functionalities. Microarray and qRT
      PCR analyses showed that 89% (56 out of 63) of Populus HD-ZIPs were duplicate
      genes that might have been retained by substantial subfunctionalization. Taken
      together, these observations may lay the foundation for future functional
      analysis of Populus HD-ZIP genes to unravel their biological roles.

PMID- 22359570
TI  - Identification of transcription factors regulating CTNNAL1 expression in human
      bronchial epithelial cells.
AB  - Adhesion molecules play important roles in airway hyperresponsiveness or airway
      inflammation. Our previous study indicated catenin alpha-like 1 (CTNNAL1), an
      alpha-catenin-related protein, was downregulated in asthma patients and animal
      model. In this study, we observed that the expression of CTNNAL1 was increased in
      lung tissue of the ozone-stressed Balb/c mice model and in acute ozone stressed
      human bronchial epithelial cells (HBEC). In order to identify the possible DNA
      binding proteins regulating the transcription of CTNNAL1 gene in HBEC, we
      designed 8 oligo- nucleotide probes corresponding to various regions of the
      CTNNAL1 promoter in electrophoretic mobility shift assays (EMSA). We detected 5
      putative transcription factors binding sites within CTNNAL1 promoter region that
      can recruit LEF-1, AP-2alpha and CREB respectively by EMSA and antibody
      supershift assay. Chromatin immunoprecipitation (ChIP) assay verified that AP-2
      alpha and LEF-1 could be recruited to the CTNNAL1 promoter. Therefore we further
      analyzed the functions of putative AP-2 and LEF-1 sites within CTNNAL1 promoter
      by site-directed mutagenesis of those sites within pGL3/FR/luc. We observed a
      reduction in human CTNNAL1 promoter activity of mutants of both AP-2alpha and LEF
      1 sites. Pre-treatment with ASOs targeting LEF-1and AP-2alpha yielded significant
      reduction of ozone-stress-induced CTNNAL1 expression. The activation of AP-2alpha
      and LEF-1, followed by CTNNAL1 expression, showed a correlation during a 16-hour
      time course. Our data suggest that a robust transcriptional CTNNAL1 up-regulation
      occurs during acute ozone-induced stress and is mediated at least in part by
      ozone-induced recruitments of LEF-1 and AP-2alpha to the human CTNNAL1 promoter.

PMID- 22359571
TI  - Morphine suppresses IFN signaling pathway and enhances AIDS virus infection.
AB  - BACKGROUND: Opioids exert a profound influence on immunomodulation and enhance
      HIV infection and replication. However, the mechanism(s) of their action remains
      to be determined. We thus investigated the impact of morphine on the
      intracellular innate antiviral immunity. METHODOLOGY/PRINCIPAL FINDINGS: Seven
      day-cultured macrophages were infected with equal amounts of cell-free HIV Bal or
      SIV Delta(B670) for 2 h at 37 degrees C after 24 h of treatment with or without
      morphine. Effect of morphine on HIV/SIV infection and replication was evaluated
      by HIV/SIV RT activity assay and indirect immunofluorescence for HIV p24 or SIV
      p28 antigen. The mRNA expression of cellular factors suppressed or induced by
      morphine treatment was analyzed by the real-time RT-PCR. We demonstrated that
      morphine treatment of human blood monocyte-derived macrophages significantly
      inhibited the expression of interferons (IFN-alpha, IFN-beta and IFN-lambda) and
      IFN-inducible genes (APOBEC3C/3F/3G and 3H). The further experiments showed that
      morphine suppressed the expression of several key elements (RIG-I and IRF-7) in
      IFN signaling pathway. In addition, morphine treatment induced the expression of
      suppressor of cytokine signaling protein-1, 2, 3 (SOCS-1, 2, 3) and protein
      inhibitors of activated STAT-1, 3, X, Y (PIAS-1, 3, X, Y), the key negative
      regulators of IFN signaling pathway. CONCLUSIONS: These findings indicate that
      morphine impairs intracellular innate antiviral mechanism(s) in macrophages,
      contributing to cell susceptibility to AIDS virus infection.

PMID- 22359572
TI  - Dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through
      inhibition of Akt/GSK-3beta and mTOR signaling pathways.
AB  - The traditional Chinese medicine component dehydrocostuslactone (DHC) isolated
      from Saussurea costus (Falc.) Lipschitz, has been shown to have anti-cancer
      activity. Angiogenesis is an essential process in the growth and progression of
      cancer. In this study, we demonstrated, for the first time, the anti-angiogenic
      mechanism of action of DHC to be via the induction of cell cycle progression at
      the G0/G1 phase due to abrogation of the Akt/glycogen synthase kinase-3beta (GSK
      3beta)/cyclin D1 and mTOR signaling pathway. First, we demonstrated that DHC has
      an anti-angiogenic effect in the matrigel-plug nude mice model and an inhibitory
      effect on human umbilical vein endothelial cell (HUVEC) proliferation and
      capillary-like tube formation in vitro. DHC caused G0/G1 cell cycle arrest, which
      was associated with the down-regulation of cyclin D1 expression, leading to the
      suppression of retinoblastoma protein phosphorylation and subsequent inhibition
      of cyclin A and cdk2 expression. With respect to the molecular mechanisms
      underlying the DHC-induced cyclin D1 down-regulation, this study demonstrated
      that DHC significantly inhibits Akt expression, resulting in the suppression of
      GSK-3beta phosphorylation and mTOR expression. These effects are capable of
      regulating cyclin D1 degradation, but they were significantly reversed by
      constitutively active myristoylated (myr)-Akt. Furthermore, the abrogation of
      tube formation induced by DHC was also reversed by overexpression of Akt. And the
      co-treatment with LiCl and DHC significantly reversed the growth inhibition
      induced by DHC. Taken together, our study has identified Akt/GSK-3beta and mTOR
      as important targets of DHC and has thus highlighted its potential application in
      angiogenesis-related diseases, such as cancer.

PMID- 22359573
TI  - Probing high affinity sequences of DNA aptamer against VEGF165.
AB  - Vascular endothelial growth factor (VEGF(165)) is a potent angiogenic mitogen
      commonly overexpressed in cancerous cells. It contains two main binding domains,
      the receptor-binding domain (RBD) and the heparin-binding domain (HBD). This
      study attempted to identify the specific sequences of the VEa5 DNA aptamer that
      exhibit high binding affinity towards the VEGF(165) protein by truncating the
      original VEa5 aptamer into different segments. Using surface plasmon resonance
      (SPR) spectroscopy for binding affinity analysis, one of the truncated aptamers
      showed a >200-fold increase in the binding affinity for HBD. This truncated
      aptamer also exhibited high specificity to HBD with negligible binding affinity
      for VEGF(121), an isoform of VEGF lacking HBD. Exposing colorectal cancer cells
      to the truncated aptamer sequence further confirmed the binding affinity and
      specificity of the aptamer to the target VEGF(165) protein. Hence, our approach
      of aptamer truncation can potentially be useful in identifying high affinity
      aptamer sequences for the biological molecules and targeting them as antagonist
      for cancer cell detection.

PMID- 22359574
TI  - Curcumin enhances neurogenesis and cognition in aged rats: implications for
      transcriptional interactions related to growth and synaptic plasticity.
AB  - BACKGROUND: Curcumin has been demonstrated to have many neuroprotective
      properties, including improvement of cognition in humans and neurogenesis in
      animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We
      assessed behavioural performance and hippocampal cell proliferation in aged rats
      after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and
      spatial memory, as well as dentate gyrate cell proliferation as compared to
      control diet rats. We also investigated underlying mechanistic pathways that
      might link curcumin treatment to increased cognition and neurogenesis via exon
      array analysis of cortical and hippocampal mRNA transcription. The results
      revealed a transcriptional network interaction of genes involved in
      neurotransmission, neuronal development, signal transduction, and metabolism in
      response to the curcumin treatment. CONCLUSIONS: The results suggest a
      neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment
      in aged rats, which may be due to its diverse effects on genes related to growth
      and plasticity.

PMID- 22359575
TI  - The functions of myosin II and myosin V homologs in tip growth and septation in
      Aspergillus nidulans.
AB  - Because of the industrial and medical importance of members of the fungal genus
      Aspergillus, there is considerable interest in the functions of cytoskeletal
      components in growth and secretion in these organisms. We have analyzed the
      genome of Aspergillus nidulans and found that there are two previously unstudied
      myosin genes, a myosin II homolog, myoB (product = MyoB) and a myosin V homolog,
      myoE (product = MyoE). Deletions of either cause significant growth defects. MyoB
      localizes in strings that coalesce into contractile rings at forming septa. It is
      critical for septation and normal deposition of chitin but not for hyphal
      extension. MyoE localizes to the Spitzenkorper and to moving puncta in the
      cytoplasm. Time-lapse imaging of SynA, a v-SNARE, reveals that in myoE deletion
      strains vesicles no longer localize to the Spitzenkorper. Tip morphology is
      slightly abnormal and branching occurs more frequently than in controls. Tip
      extension is slower than in controls, but because hyphal diameter is greater,
      growth (increase in volume/time) is only slightly reduced. Concentration of
      vesicles into the Spitzenkorper before incorporation into the plasma membrane is,
      thus, not required for hyphal growth but facilitates faster tip extension and a
      more normal hyphal shape.

PMID- 22359576
TI  - AMP-activated protein kinase plays an important evolutionary conserved role in
      the regulation of glucose metabolism in fish skeletal muscle cells.
AB  - AMPK, a master metabolic switch, mediates the observed increase of glucose uptake
      in locomotory muscle of mammals during exercise. AMPK is activated by changes in
      the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile
      activity but also by AICAR and metformin, compounds that increase glucose
      transport in mammalian muscle cells. However, the possible role of AMPK in the
      regulation of glucose metabolism in skeletal muscle has not been investigated in
      other vertebrates, including fish. In this study, we investigated the effects of
      AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout
      GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes
      regulating glucose disposal and PGC1alpha in trout myotubes derived from a
      primary muscle cell culture. We show that AICAR and metformin significantly
      stimulated glucose uptake (1.6 and 1.3 fold, respectively) and that Compound C
      completely abrogated the stimulatory effects of the AMPK activators on glucose
      uptake. The combination of insulin and AMPK activators did not result in additive
      nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes
      to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold,
      respectively). We also provide evidence suggesting that stimulation of glucose
      uptake by AMPK activators in trout myotubes may take place, at least in part, by
      increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR
      increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6
      phosphofructokinase, pyruvate kinase and citrate synthase) and mitochondrial
      biogenesis (PGC-1alpha) and did not affect glycogen content or glycogen synthase
      mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time
      in non-mammalian vertebrates, suggesting a potentially important role of AMPK in
      stimulating glucose uptake and utilization in the skeletal muscle of fish.

PMID- 22359577
TI  - CXCR4 expression in prostate cancer progenitor cells.
AB  - Tumor progenitor cells represent a population of drug-resistant cells that can
      survive conventional chemotherapy and lead to tumor relapse. However, little is
      known of the role of tumor progenitors in prostate cancer metastasis. The studies
      reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor
      dissemination, plays a role in the maintenance of prostate cancer stem-like
      cells. The CXCL4/CXCR12 pathway is activated in the CD44(+)/CD133(+) prostate
      progenitor population and affects differentiation potential, cell adhesion,
      clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies
      in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which
      targets prostate cancer stem-like cells, and the conventional chemotherapeutic
      drug Taxotere, which targets the bulk tumor, is significantly more effective in
      eradicating tumors as compared to monotherapy.

PMID- 22359578
TI  - Shape and compliance of endothelial cells after shear stress in vitro or from
      different aortic regions: scanning ion conductance microscopy study.
AB  - OBJECTIVE: To measure the elongation and compliance of endothelial cells
      subjected to different patterns of shear stress in vitro, and to compare these
      parameters with the elongation and compliance of endothelial cells from different
      regions of the intact aorta. MATERIALS AND METHODS: Porcine aortic endothelial
      cells were cultured for 6 days under static conditions or on an orbital shaker.
      The shaker generated a wave of medium, inducing pulsatile shear stress with a
      preferred orientation at the edge of the well or steadier shear stress with
      changing orientation at its centre. The topography and compliance of these cells
      and cells from the inner and outer curvature of ex vivo porcine aortic arches
      were measured by scanning ion conductance microscopy (SICM). RESULTS: Cells
      cultured under oriented shear stress were more elongated and less compliant than
      cells grown under static conditions or under shear stress with no preferred
      orientation. Cells from the outer curvature of the aorta were more elongated and
      less compliant than cells from the inner curvature. CONCLUSION: The elongation
      and compliance of cultured endothelial cells vary according to the pattern of
      applied shear stress, and are inversely correlated. A similar inverse correlation
      occurs in the aortic arch, with variation between regions thought to experience
      different haemodynamic stresses.

PMID- 22359579
TI  - RNA-seq reveals novel transcriptome of genes and their isoforms in human
      pulmonary microvascular endothelial cells treated with thrombin.
AB  - The dysregulation of vascular endothelial cells by thrombin has been implicated
      in the development of a number of pathologic disorders such as inflammatory
      conditions, cancer, diabetes, coronary heart disease. However, transcriptional
      regulation of vascular endothelial cells by thrombin is not completely
      understood. In the present study, Illumina RNA-seq was used to profile the
      transcriptome in human pulmonary microvascular endothelial cells (HMVEC-L)
      treated with thrombin for 6 h to gain insight into thrombin's direct effects on
      the endothelial function. Out of 100 million total reads from a paired end
      sequencing assay, 91-94% of the reads were aligned to over 16,000 genes in the
      reference human genome. Thrombin upregulated 150 known genes and 480 known
      isoforms, and downregulated 2,190 known genes and 3,574 known isoforms by at
      least 2 fold. Of note, thrombin upregulated 1,775 previously unknown isoforms and
      downregulated 12,202 previously unknown isoforms by at least 2 fold. Many genes
      displayed isoform specific differential expression levels and different usage of
      transcriptional start sites after the thrombin treatment. The cross comparisons
      between our RNA-seq data and those of DNA microarray analysis of either 6 h
      thrombin treated HUVEC or 5 h TNFalpha treated HMVEC have provided a significant
      overlapping list of differentially expressed genes, supporting the robust utility
      of our dataset. Further in-depth follow-up analysis of the transcriptional
      regulation reported in this study may shed light on molecular pathogenic
      mechanisms underlying thrombin mediated endothelial dysfunction in various
      diseases and provide new leads of potential therapeutic targets.

PMID- 22359580
TI  - Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis.
AB  - Inflammatory Bowel Disease--comprised of Crohn's Disease and Ulcerative Colitis
      (UC)--is a complex, multi-factorial inflammatory disorder of the gastrointestinal
      tract. In this study we have explored the utility of naturally occurring
      circulating miRNAs as potential blood-based biomarkers for non-invasive
      prediction of UC incidences. Whole genome maps of circulating miRNAs in micro
      vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed
      from a cohort of 20 UC patients and 20 normal individuals. Through Significance
      Analysis of Microarrays, a signature of 31 differentially expressed platelet
      derived miRNAs has been identified and biomarker performance estimated through a
      non-probabilistic binary linear classification using Support Vector Machines.
      Through this approach, classifier measurements reveal a predictive score of 92.8%
      accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients
      from normal individuals. Additionally, the platelet-derived biomarker signature
      can be validated at 88% accuracy through qPCR assays, and a majority of the
      miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated
      intensity based clusters. Analysis of predicted targets of these biomarkers
      reveal an enrichment of pathways associated with cytoskeleton assembly,
      transport, membrane permeability and regulation of transcription factors engaged
      in a variety of regulatory cascades that are consistent with a cell-mediated
      immune response model of intestinal inflammation. Interestingly, comparison of
      the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide
      association studies identifies a physical linkage between hsa-miR-941 and a UC
      susceptibility loci located on Chr 20. Taken together, analysis of these
      expression maps outlines a promising catalog of novel platelet-derived miRNA
      biomarkers of clinical utility and provides insight into the potential biological
      function of these candidates in disease pathogenesis.

PMID- 22359581
TI  - Th17-related genes and celiac disease susceptibility.
AB  - Th17 cells are known to be involved in several autoimmune or inflammatory
      diseases. In celiac disease (CD), recent studies suggest an implication of those
      cells in disease pathogenesis. We aimed at studying the role of genes relevant
      for the Th17 immune response in CD susceptibility. A total of 101 single
      nucleotide polymorphisms (SNPs), mainly selected to cover most of the variability
      present in 16 Th17-related genes (IL23R, RORC, IL6R, IL17A, IL17F, CCR6, IL6,
      JAK2, TNFSF15, IL23A, IL22, STAT3, TBX21, SOCS3, IL12RB1 and IL17RA), were
      genotyped in 735 CD patients and 549 ethnically matched healthy controls. Case
      control comparisons for each SNP and for the haplotypes resulting from the SNPs
      studied in each gene were performed using chi-square tests. Gene-gene
      interactions were also evaluated following different methodological approaches.
      No significant results emerged after performing the appropriate statistical
      corrections. Our results seem to discard a relevant role of Th17 cells on CD
      risk.

PMID- 22359582
TI  - The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm
      determinants in Escherichia coli.
AB  - Bacteria are often found in multicellular communities known as biofilms, which
      constitute a resistance form against environmental stresses. Extracellular
      adhesion and cell aggregation factors, responsible for bacterial biofilm
      formation and maintenance, are tightly regulated in response to physiological and
      environmental cues. We show that, in Escherichia coli, inactivation of genes
      belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs
      production of curli fibers and cellulose, important components of the bacterial
      biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus
      preventing production of the biofilm master regulator CsgD protein. Supplementing
      growth media with exogenous uracil, which can be converted to UMP through the
      pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli
      production. In addition, however, exogenous uracil triggers cellulose production,
      particularly in strains defective in either carB or pyrB genes, which encode
      enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results
      indicate the existence of tight and complex links between pyrimidine metabolism
      and curli/cellulose production: transcription of the csgDEFG operon responds to
      pyrimidine nucleotide availability, while cellulose production is triggered by
      exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate
      that perturbations in the UMP biosynthetic pathways allow the bacterial cell to
      sense signals such as starvation, nucleic acids degradation, and availability of
      exogenous pyrimidines, and to adapt the production of the extracellular matrix to
      the changing environmental conditions.

PMID- 22359583
TI  - The genome sequence of Polymorphum gilvum SL003B-26A1(T) reveals its genetic
      basis for crude oil degradation and adaptation to the saline soil.
AB  - Polymorphum gilvum SL003B-26A1(T) is the type strain of a novel species in the
      recently published novel genus Polymorphum isolated from saline soil contaminated
      with crude oil. It is capable of using crude oil as the sole carbon and energy
      source and can adapt to saline soil at a temperature of 45 degrees C. The
      Polymorphum gilvum genome provides a genetic basis for understanding how the
      strain could degrade crude oil and adapt to a saline environment. Genome analysis
      revealed the versatility of the strain for emulsifying crude oil, metabolizing
      aromatic compounds (a characteristic specific to the Polymorphum gilvum genome in
      comparison with other known genomes of oil-degrading bacteria), as well as
      possibly metabolizing n-alkanes through the LadA pathway. In addition, COG
      analysis revealed Polymorphum gilvum SL003B-26A1(T) has significantly higher
      abundances of the proteins responsible for cell motility, lipid transport and
      metabolism, and secondary metabolite biosynthesis, transport and catabolism than
      the average levels found in all other genomes sequenced thus far, but lower
      abundances of the proteins responsible for carbohydrate transport and metabolism,
      defense mechanisms, and translation than the average levels. These traits support
      the adaptability of Polymorphum gilvum to a crude oil-contaminated saline
      environment. The Polymorphum gilvum genome could serve as a platform for further
      study of oil-degrading microorganisms for bioremediation and microbial-enhanced
      oil recovery in harsh saline environments.

PMID- 22359584
TI  - Defining components of the beta-catenin destruction complex and exploring its
      regulation and mechanisms of action during development.
AB  - BACKGROUND: A subset of signaling pathways play exceptionally important roles in
      embryonic and post-embryonic development, and mis-regulation of these pathways
      occurs in most human cancers. One such pathway is the Wnt pathway. The primary
      mechanism keeping Wnt signaling off in the absence of ligand is regulated
      proteasomal destruction of the canonical Wnt effector betacatenin (or its fly
      homolog Armadillo). A substantial body of evidence indicates that SCF(betaTrCP)
      mediates betacat destruction, however, an essential role for Roc1 has not been
      demonstrated in this process, as would be predicted. In addition, other E3
      ligases have also been proposed to destroy betacat, suggesting that betacat
      destruction may be regulated differently in different tissues.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we used cultured Drosophila cells, human
      colon cancer cells, and Drosophila embryos and larvae to explore the machinery
      that targets Armadillo for destruction. Using RNAi in Drosophila S2 cells to
      examine which SCF components are essential for Armadillo destruction, we find
      that Roc1/Roc1a is essential for regulating Armadillo stability, and that in
      these cells the only F-box protein playing a detectable role is Slimb. Second, we
      find that while embryonic and larval Drosophila tissues use the same destruction
      complex proteins, the response of these tissues to destruction complex
      inactivation differs, with Armadillo levels more elevated in embryos. We provide
      evidence consistent with the possibility that this is due to differences in
      armadillo mRNA levels. Third, we find that there is no correlation between the
      ability of different APC2 mutant proteins to negatively regulate Armadillo
      levels, and their recently described function in positively-regulating Wnt
      signaling. Finally, we demonstrate that APC proteins lacking the N-terminal
      Armadillo-repeat domain cannot restore Armadillo destruction but retain residual
      function in negatively-regulating Wnt signaling. CONCLUSIONS/SIGNIFICANCE: We use
      these data to refine our model for how Wnt signaling is regulated during normal
      development.

PMID- 22359585
TI  - A high-throughput screen identifies a new natural product with broad-spectrum
      antibacterial activity.
AB  - Due to the inexorable invasion of our hospitals and communities by drug-resistant
      bacteria, there is a pressing need for novel antibacterial agents. Here we report
      the development of a sensitive and robust but low-tech and inexpensive high
      throughput metabolic screen for novel antibiotics. This screen is based on a
      colorimetric assay of pH that identifies inhibitors of bacterial sugar
      fermentation. After validation of the method, we screened over 39,000 crude
      extracts derived from organisms that grow in the diverse ecosystems of Costa Rica
      and identified 49 with reproducible antibacterial effects. An extract from an
      endophytic fungus was further characterized, and this led to the discovery of
      three novel natural products. One of these, which we named mirandamycin, has
      broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas
      aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and
      Mycobacterium tuberculosis. This demonstrates the power of simple high throughput
      screens for rapid identification of new antibacterial agents from environmental
      samples.

PMID- 22359586
TI  - Impact of the herbal medicine Sophora flavescens on the oral pharmacokinetics of
      indinavir in rats: the involvement of CYP3A and P-glycoprotein.
AB  - Sophora flavescens is a Chinese medicinal herb used for the treatment of
      gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral
      hepatitis. In this study the herb-drug interactions between S. flavescens and
      indinavir, a protease inhibitor for HIV treatment, were evaluated in rats.
      Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg,
      p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a
      dose-dependent decrease of plasma indinavir concentrations, with 55%-83% decrease
      in AUC(0-infinity) and 38%-78% reduction in C(max). The CL (Clearance)/F
      (fraction of dose available in the systemic circulation) increased up to 7.4-fold
      in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased
      indinavir concentrations, while the ethyl acetate fraction of Sophora extract had
      no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir
      in faeces was increased after Sophora treatment. Compared to the controls,
      multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp
      in the small intestine and liver. In addition, Sophora treatment increased
      intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2
      expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by
      Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats.
      All available data demonstrated that Sophora flavescens reduced plasma indinavir
      concentration after multiple concomitant doses, possibly through hepatic CYP3A
      activity and induction of intestinal and hepatic P-gp. The animal study would be
      useful for predicting potential interactions between natural products and oral
      pharmaceutics and understanding the mechanisms prior to human studies. Results in
      the current study suggest that patients using indinavir might be cautioned in the
      use of S. flavescens extract or Sophora-derived products.

PMID- 22359587
TI  - Mitochondria express alpha7 nicotinic acetylcholine receptors to regulate Ca2+
      accumulation and cytochrome c release: study on isolated mitochondria.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that
      mediate synaptic transmission in the muscle and autonomic ganglia and regulate
      transmitter release in the brain. The nAChRs composed of alpha7 subunits are also
      expressed in non-excitable cells to regulate cell survival and proliferation. Up
      to now, functional alpha7 nAChRs were found exclusively on the cell plasma
      membrane. Here we show that they are expressed in mitochondria and regulate early
      pro-apoptotic events like cytochrome c release. The binding of alpha7-specific
      antibody with mouse liver mitochondria was revealed by electron microscopy. Outer
      membranes of mitochondria from the wild-type and beta2-/- but not alpha7-/- mice
      bound alpha7 nAChR-specific antibody and toxins: FITC-labeled alpha-cobratoxin or
      Alexa 555-labeled alpha-bungarotoxin. alpha7 nAChR agonists (1 uM acetylcholine,
      10 uM choline or 30 nM PNU-282987) impaired intramitochondrial Ca(2+)
      accumulation and significantly decreased cytochrome c release stimulated with
      either 90 uM CaCl(2) or 0.5 mM H(2)O(2). alpha7-specific antagonist
      methyllicaconitine (50 nM) did not affect Ca(2+) accumulation in mitochondria but
      attenuated the effects of agonists on cytochrome c release. Inhibitor of voltage
      dependent anion channel (VDAC) 4,4'-diisothio-cyano-2,2'-stilbene disulfonic acid
      (0.5 uM) decreased cytochrome c release stimulated with apoptogens similarly to
      alpha7 nAChR agonists, and VDAC was co-captured with the alpha7 nAChR from
      mitochondria outer membrane preparation in both direct and reverse sandwich
      ELISA. It is concluded that alpha7 nAChRs are expressed in mitochondria outer
      membrane to regulate the VDAC-mediated Ca(2+) transport and mitochondrial
      permeability transition.

PMID- 22359588
TI  - Anti-arthritic effects of magnolol in human interleukin 1beta-stimulated
      fibroblast-like synoviocytes and in a rat arthritis model.
AB  - Fibroblast-like synoviocytes (FLS) play an important role in the pathologic
      processes of destructive arthritis by producing a number of catabolic cytokines
      and metalloproteinases (MMPs). The expression of these mediators is controlled at
      the transcriptional level. The purposes of this study were to evaluate the anti
      arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol), the major
      bioactive component of the bark of Magnolia officinalis, by examining its
      inhibitory effects on inflammatory mediator secretion and the NF-kappaB and AP-1
      activation pathways and to investigate its therapeutic effects on the development
      of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was
      tested on interleukin (IL)-1beta-stimulated FLS by measuring levels of IL-6,
      cyclooxygenase-2, prostaglandin E(2), and matrix metalloproteinases (MMPs) by
      ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1beta-stimulated
      cytokine expression were performed using Western blots, reporter gene assay,
      electrophoretic mobility shift assay, and confocal microscope analysis. The in
      vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium
      butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1beta
      (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5
      25 ug/mL). In clarifying the mechanisms involved, magnolol was found to inhibit
      the IL-1beta-induced activation of the IKK/IkappaB/NF-kappaB and MAPKs pathways
      by suppressing the nuclear translocation and DNA binding activity of both
      transcription factors. In the animal model, magnolol (100 mg/kg) significantly
      inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate
      that magnolol inhibits the development of arthritis, suggesting that it might
      provide a new therapeutic approach to inflammatory arthritis diseases.

PMID- 22359589
TI  - Actin filament attachments for sustained motility in vitro are maintained by
      filament bundling.
AB  - We reconstructed cellular motility in vitro from individual proteins to
      investigate how actin filaments are organized at the leading edge. Using total
      internal reflection fluorescence microscopy of actin filaments, we tested how
      profilin, Arp2/3, and capping protein (CP) function together to propel thin glass
      nanofibers or beads coated with N-WASP WCA domains. Thin nanofibers produced wide
      comet tails that showed more structural variation in actin filament organization
      than did bead substrates. During sustained motility, physiological concentrations
      of Mg(2+) generated actin filament bundles that processively attached to the
      nanofiber. Reduction of total Mg(2+) abolished particle motility and actin
      attachment to the particle surface without affecting actin polymerization, Arp2/3
      nucleation, or filament capping. Analysis of similar motility of microspheres
      showed that loss of filament bundling did not affect actin shell formation or
      symmetry breaking but eliminated sustained attachments between the comet tail and
      the particle surface. Addition of Mg(2+), Lys-Lys(2+), or fascin restored both
      comet tail attachment and sustained particle motility in low Mg(2+) buffers. TIRF
      microscopic analysis of filaments captured by WCA-coated beads in the absence of
      Arp2/3, profilin, and CP showed that filament bundling by polycation or fascin
      addition increased barbed end capture by WCA domains. We propose a model in which
      CP directs barbed ends toward the leading edge and polycation-induced filament
      bundling sustains processive barbed end attachment to the leading edge.

PMID- 22359590
TI  - Decidual-secreted factors alter invasive trophoblast membrane and secreted
      proteins implying a role for decidual cell regulation of placentation.
AB  - Inadequate or inappropriate implantation and placentation during the
      establishment of human pregnancy is thought to lead to first trimester
      miscarriage, placental insufficiency and other obstetric complications. To create
      the placental blood supply, specialized cells, the 'extravillous trophoblast'
      (EVT) invade through the differentiated uterine endometrium (the decidua) to
      engraft and remodel uterine spiral arteries. We hypothesized that decidual
      factors would regulate EVT function by altering the production of EVT membrane
      and secreted factors. We used a proteomics approach to identify EVT membrane and
      secreted proteins regulated by decidual cell factors. Human endometrial stromal
      cells were decidualized in vitro by treatment with estradiol (10(-8) M),
      medroxyprogesterone acetate (10(-7) M) and cAMP (0.5 mM) for 14 days. Conditioned
      media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM)
      of treatment. Isolated primary EVT cultured on MatrigelTM were treated with media
      control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated
      for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before
      trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14
      not previously known to be expressed in the placenta and 12 which had previously
      been associated with diseases of pregnancy including preeclampsia. Profilin 1,
      lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1
      (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was
      validated by immunhistochemistry. Decidual CM regulation in vitro was validated
      by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non
      decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate.
      Here, non-decidualized factors induced protease expression by EVT suggesting that
      non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a
      pro-inflammatory condition. Overall, we have demonstrated the potential of a
      proteomics approach to identify novel proteins expressed by EVT and to uncover
      the mechanisms leading to disease states.

PMID- 22359592
TI  - Mirror, mirror on the wall, how does my brain recognize my image at all?
AB  - For decades researchers have used mirrors to study self-recognition. However,
      attempts to identify neural processes underlying this ability have used
      photographs instead. Here we used event related potentials (ERPs) to compare self
      face recognition in photographs versus mirrors and found distinct neural
      signatures. Measures of visual self-recognition are therefore not independent of
      the medium employed.

PMID- 22359591
TI  - No differential regulation of dopamine transporter (DAT) and vesicular monoamine
      transporter 2 (VMAT2) binding in a primate model of Parkinson disease.
AB  - Radioligands for DAT and VMAT2 are widely used presynaptic markers for assessing
      dopamine (DA) nerve terminals in Parkinson disease (PD). Previous in vivo imaging
      and postmortem studies suggest that these transporter sites may be regulated as
      the numbers of nigrostriatal neurons change in pathologic conditions. To
      investigate this issue, we used in vitro quantitative autoradioradiography to
      measure striatal DAT and VMAT2 specific binding in postmortem brain from 14
      monkeys after unilateral internal carotid artery infusion of 1-Methyl-4-Phenyl
      1,2,3,6-tetrahydropyridine (MPTP) with doses varying from 0 to 0.31 mg/kg.
      Quantitative estimates of the number of tyrosine hydroxylase (TH)-immunoreactive
      (ir) neurons in substantia nigra (SN) were determined with unbiased stereology,
      and quantitative autoradiography was used to measure DAT and VMAT2 striatal
      specific binding. Striatal VMAT2 and DAT binding correlated with striatal DA
      (r(s) = 0.83, r(s) = 0.80, respectively, both with n = 14, p<0.001) but only with
      nigra TH-ir cells when nigral cell loss was 50% or less (r = 0.93, n = 8, p =
      0.001 and r = 0.91, n = 8, p = 0.002 respectively). Reduction of VMAT2 and DAT
      striatal specific binding sites strongly correlated with each other (r = 0.93, n
      = 14, p<0.0005). These similar changes in DAT and VMAT2 binding sites in the
      striatal terminal fields of the surviving nigrostriatal neurons demonstrate that
      there is no differential regulation of these two sites at 2 months after MPTP
      infusion.

PMID- 22359593
TI  - Co-immunization with multimeric scaffolds and DNA rapidly induces potent
      autologous HIV-1 neutralizing antibodies and CD8+ T cells.
AB  - To obtain proof of concept for HIV vaccines, we generated recombinant multimeric
      particles displaying the HIV-1 Envelope (Env) third hypervariable region (V3) as
      an N-terminal fusion protein on the E2 subunit of the pyruvate dehydrogenase
      complex of Geobacillus stearothermophilus. The E2 scaffold self-assembles into a
      60-mer core that is 24 nm in diameter, with a molecular weight of 1.5 MDa,
      similar to a virus like particle with up to 60 copies of a heterologous protein
      accessible on the surface. Env(V3)-E2 multimers were tested alone and in
      combination with Env(gp160) DNA in mice and rabbits. Following two or more co
      immunizations with Env(V3)-E2 and Env gp160 DNA, all 18 rabbits developed potent
      autologous neutralizing antibodies specific for V3 in six weeks. These
      neutralizing antibodies were sustained for 16 weeks without boosting, and
      comparable responses were obtained when lipopolysaccharide, a contaminant from
      expression in E. coli, was removed. Co-immunizations of Env(V3)-E2 and DNA
      expressing gp160 elicited moderate CD8-specific responses and Env-specific
      antibodies in mice. Co-immunization with DNA and E2 was superior to individual or
      sequential vaccination with these components in eliciting both neutralizing
      antibodies in rabbits and CD8(+) T cell responses in mice. Co-immunization with
      DNA and multimeric E2 scaffolds appears to offer a highly effective means of
      eliciting rapid, specific, and sustained immune responses that may be a useful
      approach for other vaccine targets.

PMID- 22359595
TI  - Endothelial microparticles (EMP) for the assessment of endothelial function: an
      in vitro and in vivo study on possible interference of plasma lipids.
AB  - BACKGROUND: Circulating endothelial microparticles (EMP) reflect the condition of
      the endothelium and are of increasing interest in cardiovascular and inflammatory
      diseases. Recently, increased numbers of EMP following oral fat intake, possibly
      due to acute endothelial injury, have been reported. On the other hand, the
      direct interference of lipids with the detection of EMP has been suggested. This
      study aimed to investigate the effect of lipid-rich solutions, commonly
      administered in clinical practice, on the detection, both in vitro and in vivo,
      of EMP. METHODS: For the in vitro assessment, several lipid-rich solutions were
      added to whole blood of healthy subjects (n = 8) and patients with coronary heart
      disease (n = 5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow
      cytometry. For the in vivo study, healthy volunteers were evaluated on 3
      different study-days: baseline evaluation, following lipid infusion and after a
      NaCl infusion. EMP quantification, lipid measurements and peripheral arterial
      tonometry were performed on each day. RESULTS: Both in vitro addition and in vivo
      administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from
      272.6 to 90.6/ul PPP, respectively, p = 0.001 and p = 0.012). The EMP number
      correlated inversely with the concentration of triglycerides, both in vitro and
      in vivo (r = -0.707 and -0.589, p<0.001 and p = 0.021, respectively). The
      validity of EMP as a marker of endothelial function is supported by their inverse
      relationship with the reactive hyperemia index (r = -0.758, p = 0.011). This
      inverse relation was confounded by the intravenous administration of lipids.
      CONCLUSION: The confounding effect of high circulating levels of lipids, commonly
      found in patients that receive intravenous lipid-based solutions, should be taken
      into account when flow cytometry is used to quantify EMP.

PMID- 22359594
TI  - Calcineurin inhibitors suppress cytokine production from memory T cells and
      differentiation of naive T cells into cytokine-producing mature T cells.
AB  - T cells have been classified as belonging to the Th1 or Th2 subsets according to
      the production of defining cytokines such as IFN-gamma and IL-4. The discovery of
      the Th17 lineage and regulatory T cells shifted the simple concept of the Th1/Th2
      balance into a 4-way mechanistic pathway of local and systemic immunological
      activity. Clinically, the blockage of cytokine signals or non-specific
      suppression of cytokine predominance by immunosuppressants is the first-line
      treatment for inflammatory T cell-mediated disorders. Cyclosporine A (CsA) and
      Tacrolimus (Tac) are commonly used immunosuppressants for the treatment of
      autoimmune disease, psoriasis, and atopic disorders. Many studies have shown that
      these compounds suppress the activation of the calcium-dependent phosphatase
      calcineurin, thereby inhibiting T-cell activation. Although CsA and Tac are
      frequently utilized, their pharmacological mechanisms have not yet been fully
      elucidated.In the present study, we focused on the effects of CsA and Tac on
      cytokine secretion from purified human memory CD4(+)T cells and the
      differentiation of naive T cells into cytokine-producing memory T cells. CsA or
      Tac significantly inhibited IFN-gamma, IL-4, and IL-17 production from memory T
      cells. These compounds also inhibited T cell differentiation into the Th1, Th2,
      and Th17 subsets, even when used at a low concentration. This study provided
      critical information regarding the clinical efficacies of CsA and Tac as
      immunosuppressants.

PMID- 22359596
TI  - Metabolite profiling of Alzheimer's disease cerebrospinal fluid.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive loss of cognitive functions. Today the diagnosis of AD relies on
      clinical evaluations and is only late in the disease. Biomarkers for early
      detection of the underlying neuropathological changes are still lacking and the
      biochemical pathways leading to the disease are still not completely understood.
      The aim of this study was to identify the metabolic changes resulting from the
      disease phenotype by a thorough and systematic metabolite profiling approach. For
      this purpose CSF samples from 79 AD patients and 51 healthy controls were
      analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC
      MS/MS) in conjunction with univariate and multivariate statistical analyses. In
      total 343 different analytes have been identified. Significant changes in the
      metabolite profile of AD patients compared to healthy controls have been
      identified. Increased cortisol levels seemed to be related to the progression of
      AD and have been detected in more severe forms of AD. Increased cysteine
      associated with decreased uridine was the best paired combination to identify
      light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of
      patients, sensitivity and specificity above 80% were obtained for several
      combinations of three to five metabolites, including cortisol and various amino
      acids, in addition to cysteine and uridine.

PMID- 22359597
TI  - Impact of macrophage inflammatory protein-1alpha deficiency on atherosclerotic
      lesion formation, hepatic steatosis, and adipose tissue expansion.
AB  - Macrophage inflammatory protein-1alpha (CCL3) plays a well-known role in
      infectious and viral diseases; however, its contribution to atherosclerotic
      lesion formation and lipid metabolism has not been determined. Low density
      lipoprotein receptor deficient (LDLR(-/-)) mice were transplanted with bone
      marrow from CCL3(-/-) or C57BL/6 wild type donors. After 6 and 12 weeks on
      western diet (WD), recipients of CCL3(-/-) marrow demonstrated lower plasma
      cholesterol and triglyceride concentrations compared to recipients of C57BL/6
      marrow. Atherosclerotic lesion area was significantly lower in female CCL3(-/-)
      recipients after 6 weeks and in male CCL3(-/-) recipients after 12 weeks of WD
      feeding (P<0.05). Surprisingly, male CCL3(-/-) recipients had a 50% decrease in
      adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were
      also significantly lower. These results were specific to CCL3, as LDLR(-/-)
      recipients of monocyte chemoattractant protein(-/-) (CCL2) marrow were not
      protected from the metabolic consequences of high fat feeding. Despite these
      improvements in LDLR(-/-) recipients of CCL3(-/-) marrow in the bone marrow
      transplantation (BMT) model, double knockout mice, globally deficient in both
      proteins, did not have decreased body weight, plasma lipids, or atherosclerosis
      compared with LDLR(-/-) controls. Finally, there were no differences in myeloid
      progenitors or leukocyte populations, indicating that changes in body weight and
      plasma lipids in CCL3(-/-) recipients was not due to differences in
      hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid
      metabolism in hyperlipidemic mice following hematopoietic reconstitution.

PMID- 22359598
TI  - ER stress negatively modulates the expression of the miR-199a/214 cluster to
      regulates tumor survival and progression in human hepatocellular cancer.
AB  - BACKGROUND: Recent studies have emphasized causative links between microRNAs
      (miRNAs) deregulation and tumor development. In hepatocellular carcinoma (HCC),
      more and more miRNAs were identified as diagnostic and prognostic cancer
      biomarkers, as well as additional therapeutic tools. This study aimed to
      investigate the functional significance and regulatory mechanism of the miR
      199a2/214 cluster in HCC progression. METHODS AND FINDINGS: In this study, we
      showed that miR-214, as well as miR-199a-3p and miR-199a-5p levels were
      significantly reduced in the majority of examined 23 HCC tissues and HepG2 and
      SMMC-7721 cell lines, compared with their nontumor counterparts. To further
      explore the role of miR-214 in hepatocarcinogenesis, we disclosed that the ER
      stress-induced pro-survival factor XBP-1 is a target of miR-214 by using western
      blot assay and luciferase reporter assay. Re-expression of miR-214 in HCC cell
      lines (HepG2 and SMMC-7721) inhibited proliferation and induced apoptosis.
      Furthermore, ectopic expression of miR-214 dramatically suppressed the ability of
      HCC cells to form colonies in vitro and to develop tumors in a subcutaneous
      xenotransplantation model of the BALB/c athymic nude mice. Moreover,
      reintroduction of XBP-1s attenuated miR-214-mediated suppression of HCC cells
      proliferation, colony and tumor formation. To further understand the mechanism of
      the miR-199a/214 cluster down-expression in HCC, we found that thapsigargin (TG)
      and tunicamycin (TM) or hypoxia-induced unfolded protein response (UPR)
      suppresses the expression of the miR-199a/214 cluster in HCC cells. By promoter
      analysis of the miR-199a2/214 gene, we conjectured NFkappaB as a potential
      negative regulator. We further found that UPR and LPS-induced NFkappaB activation
      suppressed miR-199a2/214 transcription, and this suppression was reversed by
      NFkappaB inhibition in HCC cells. CONCLUSIONS: Our study suggest that modulation
      of miR-214 levels may provide a new therapeutic approach for cancer treatment and
      revealed that UPR may offer a new explanation for why the miR-199a/214 cluster
      were down-regulated in the progression in HCC.

PMID- 22359599
TI  - Risk factors of household transmission of pandemic (H1N1) 2009 among patients
      treated with antivirals: a prospective study at a primary clinic in Japan.
AB  - BACKGROUND: Household transmission of influenza can affect the daily lives of
      patients and their families and be a trigger for community transmission, thus it
      is necessary to take precautions to prevent household transmission. We aimed to
      determine the risks of household transmission of pandemic (H1N1) 2009 influenza
      virus from an index patient who visited a primary clinic and was treated with
      antiviral drugs. METHODS: We followed up all the patients who were diagnosed with
      influenza A by rapid diagnostic test with a questionnaire or interview from July
      2009 to April 2010. Secondary cases were defined as patients visiting the clinic
      or other clinics and being positive for influenza A by rapid diagnostic test
      within 7 days of onset of an index patient. Logistic regression analysis was used
      to explore the association between household transmission and the studied
      variables. RESULTS: We recruited 591 index patients and 1629 household contacts.
      The crude secondary attack rate was 7.3% [95% confidence interval (CI): 6.1-8.7].
      Age of index patients (0-6 years old: odds ratio 2.56; 95% CI: 1.31-4.01; 7-12
      years old: 2.44, 1.31-3.72; 30-39 years old 3.88; 2.09-5.21; 40 years old or more
      2.76; 1.17-4.53) and number of household members with five or more (3.09, 2.11
      4.07), medication started >=48 hours from the onset of fever (2.38, 1.17-3.87)
      were significantly associated with household transmission. CONCLUSIONS: Household
      transmission was associated with index patients aged <=12 years old and adults
      >=30 years with children, with more than five persons in the household, and
      medication initiated >=48 hours from the onset of fever among the population, in
      which, antiviral treatment was given to all patients. We need to warn patients at
      high risk of household transmission to take additional precautions.

PMID- 22359600
TI  - Identifying insects with incomplete DNA barcode libraries, African fruit flies
      (Diptera: Tephritidae) as a test case.
AB  - We propose a general working strategy to deal with incomplete reference libraries
      in the DNA barcoding identification of species. Considering that (1) queries with
      a large genetic distance with their best DNA barcode match are more likely to be
      misidentified and (2) imposing a distance threshold profitably reduces
      identification errors, we modelled relationships between identification
      performances and distance thresholds in four DNA barcode libraries of Diptera (n
      = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602
      DNA barcodes). In all cases, more restrictive distance thresholds produced a
      gradual increase in the proportion of true negatives, a gradual decrease of false
      positives and more abrupt variations in the proportions of true positives and
      false negatives. More restrictive distance thresholds improved precision, yet
      negatively affected accuracy due to the higher proportions of queries discarded
      (viz. having a distance query-best match above the threshold). Using a simple
      linear regression we calculated an ad hoc distance threshold for the tephritid
      library producing an estimated relative identification error <0.05. According to
      the expectations, when we used this threshold for the identification of 188
      independently collected tephritids, less than 5% of queries with a distance query
      best match below the threshold were misidentified. Ad hoc thresholds can be
      calculated for each particular reference library of DNA barcodes and should be
      used as cut-off mark defining whether we can proceed identifying the query with a
      known estimated error probability (e.g. 5%) or whether we should discard the
      query and consider alternative/complementary identification methods.

PMID- 22359601
TI  - Genetic and biochemical characterization of the cell wall hydrolase activity of
      the major secreted protein of Lactobacillus rhamnosus GG.
AB  - Lactobacillus rhamnosus GG (LGG) produces two major secreted proteins, designated
      here Msp1 (LGG_00324 or p75) and Msp2 (LGG_00031 or p40), which have been
      reported to promote the survival and growth of intestinal epithelial cells.
      Intriguingly, although each of these proteins shares homology with cell wall
      hydrolases, a physiological function that correlates with such an enzymatic
      activity remained to be substantiated in LGG. To investigate the bacterial
      function, we constructed knock-out mutants in the corresponding genes aiming to
      establish a genotype to phenotype relation. Microscopic examination of the msp1
      mutant showed the presence of rather long and overly extended cell chains, which
      suggests that normal daughter cell separation is hampered. Subsequent observation
      of the LGG wild-type cells by immunofluorescence microscopy revealed that the
      Msp1 protein accumulates at the septum of exponential-phase cells. The cell wall
      hydrolyzing activity of the Msp1 protein was confirmed by zymogram analysis.
      Subsequent analysis by RP-HPLC and mass spectrometry of the digestion products of
      LGG peptidoglycan (PG) by Msp1 indicated that the Msp1 protein has D-glutamyl-L
      lysyl endopeptidase activity. Immunofluorescence microscopy and the failure to
      construct a knock-out mutant suggest an indispensable role for Msp2 in priming
      septum formation in LGG.

PMID- 22359602
TI  - Palphax6 expression in postmitotic neurons mediates the growth of axons in
      response to SFRP1.
AB  - During development, the mechanisms that specify neuronal subclasses are coupled
      to those that determine their axonal response to guidance cues. Pax6 is a
      homedomain transcription factor required for the specification of a variety of
      neural precursors. After cell cycle exit, Pax6 expression is often shut down in
      the precursor progeny and most postmitotic neurons no longer express detectable
      levels of the protein. There are however exceptions and high Pax6 protein levels
      are found, for example, in postmitotic retinal ganglion cells (RGCs),
      dopaminergic neurons of the olfactory bulb and the limbic system in the
      telencephalon. The function of Pax6 in these differentiating neurons remains
      mostly elusive. Here, we demonstrate that Pax6 mediates the response of growing
      axons to SFRP1, a secreted molecule expressed in several Pax6-positive forebrain
      territories. Forced expression of Pax6 in cultured postmitotic cortical neurons,
      which do not normally express Pax6, was sufficient to increment axonal length.
      Growth was blocked by the addition of anti-SFRP1 antibodies, whereas exogenously
      added SFRP1 increased axonal growth of Pax6-transfected neurons but not that of
      control or untransfected cortical neurons. In the reverse scenario, shRNA
      mediated knock-down of Pax6 in mouse retinal explants specifically abolished RGCs
      axonal growth induced by SFRP1, but had no effect on RGCs differentiation and it
      did not modify the effect of Shh or Netrin on axon growth. Taken together these
      results demonstrate that expression of Pax6 is necessary and sufficient to render
      postmitotic neurons competent to respond to SFRP1. These results reveal a novel
      and unexpected function of Pax6 in postmitotic neurons and situate Pax6 and SFRP1
      as pair regulators of axonal connectivity.

PMID- 22359603
TI  - The orphan nuclear receptor LRH-1 and ERalpha activate GREB1 expression to induce
      breast cancer cell proliferation.
AB  - BACKGROUND: Liver Receptor Homolog 1 (LRH-1, NR5A2) is an orphan nuclear receptor
      that is over-expressed in cancers in tissues such as the breast, colon and
      pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis
      and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell
      cycle progression. High LRH-1 expression is demonstrated in breast cancers,
      positively correlating with ERalpha status and aromatase activity. LRH-1
      dependent cellular mechanisms in breast cancer epithelial cells are poorly
      defined. Hence in the present study we investigated the actions of LRH-1 in
      estrogen receptor alpha (ERalpha) positive breast cancer cells. RESULTS: The
      study aimed to investigate LRH-1 dependent mechanisms that promote breast cancer
      proliferation. We identified that LRH-1 regulated the expression of Growth
      Regulation by Estrogen in Breast Cancer 1 (GREB1) in MCF-7 and MDA-MB-231 cells.
      Over-expression of LRH-1 increased GREB1 mRNA levels while knockdown of LRH-1
      reduced its expression. GREB1 is a well characterised ERalpha target gene, with
      three estrogen response elements (ERE) located on its promoter. Chromatin
      immunoprecipitation studies provided evidence of the co-localisation of LRH-1 and
      ERalpha at all three EREs. With electrophoretic mobility shift assays, we
      demonstrated direct binding of LRH-1 to EREs located on GREB1 and Trefoil Factor
      1 (TFF1, pS2) promoters. LRH-1 and ERalpha co-operatively activated transcription
      of ERE luciferase reporter constructs suggesting an overlap in regulation of
      target genes in breast cancer cells. Over-expression of LRH-1 resulted in an
      increase in cell proliferation. This effect was more pronounced with estradiol
      treatment. In the presence of ICI 182,780, an ERalpha antagonist, LRH-1 still
      induced proliferation. CONCLUSIONS: We conclude that in ER-positive breast cancer
      cells, LRH-1 promotes cell proliferation by enhancing ERalpha mediated
      transcription of target genes such as GREB-1. Collectively these findings
      indicate the importance of LRH-1 in the progression of hormone-dependent breast
      cancer and implicate LRH-1 as a potential avenue for drug development.

PMID- 22359604
TI  - Reciprocal effects of litter from exotic and congeneric native plant species via
      soil nutrients.
AB  - Invasive exotic plant species are often expected to benefit exclusively from
      legacy effects of their litter inputs on soil processes and nutrient
      availability. However, there are relatively few experimental tests determining
      how litter of exotic plants affects their own growth conditions compared to
      congeneric native plant species. Here, we test how the legacy of litter from
      three exotic plant species affects their own performance in comparison to their
      congeneric natives that co-occur in the invaded habitat. We also analyzed litter
      effects on soil processes. In all three comparisons, soil with litter from exotic
      plant species had the highest respiration rates. In two out of the three exotic
      native species comparisons, soil with litter from exotic plant species had higher
      inorganic nitrogen concentrations than their native congener, which was likely
      due to higher initial litter quality of the exotics. When litter from an exotic
      plant species had a positive effect on itself, it also had a positive effect on
      its native congener. We conclude that exotic plant species develop a legacy
      effect in soil from the invaded range through their litter inputs. This litter
      legacy effect results in altered soil processes that can promote both the exotic
      plant species and their native congener.

PMID- 22359605
TI  - Comparative genomics of 2009 seasonal plague (Yersinia pestis) in New Mexico.
AB  - Plague disease caused by the gram-negative bacterium Yersinia pestis routinely
      affects animals and occasionally humans, in the western United States. The
      strains native to the North American continent are thought to be derived from a
      single introduction in the late 19(th) century. The degree to which these
      isolates have diverged genetically since their introduction is not clear, and new
      genomic markers to assay the diversity of North American plague are highly
      desired. To assay genetic diversity of plague isolates within confined geographic
      areas, draft genome sequences were generated by 454 pyrosequencing from nine
      environmental and clinical plague isolates. In silico assemblies of Variable
      Number Tandem Repeat (VNTR) loci were compared to laboratory-generated profiles
      for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels)
      were compared to previously sequenced Y. pestis isolates. The resulting panel of
      mutations allowed clustering of the strains and tracing of the most likely
      evolutionary trajectory of the plague strains. The sequences also allowed the
      identification of new putative SNPs that differentiate the 2009 isolates from
      previously sequenced plague strains and from each other. In addition, new
      insertion points for the abundant insertion sequences (IS) of Y. pestis are
      present that allow additional discrimination of strains; several of these new
      insertions potentially inactivate genes implicated in virulence. These sequences
      enable whole-genome phylogenetic analysis and allow the unbiased comparison of
      closely related isolates of a genetically monomorphic pathogen.

PMID- 22359606
TI  - A high-resolution shape fitting and simulation demonstrated equatorial cell
      surface softening during cytokinesis and its promotive role in cytokinesis.
AB  - Different models for animal cell cytokinesis posit that the stiffness of the
      equatorial cortex is either increased or decreased relative to the stiffness of
      the polar cortex. A recent work has suggested that the critical cytokinesis
      signaling complex centralspindlin may reduce the stiffness of the equatorial
      cortex by inactivating the small GTPase Rac. To determine if such a reduction
      occurs and if it depends on centralspindlin, we devised a method to estimate
      cortical bending stiffness with high spatio-temporal resolution from in vivo cell
      shapes. Using the early Caenorhabditis elegans embryo as a model, we show that
      the stiffness of the equatorial cell surface is reduced during cytokinesis,
      whereas the stiffness of the polar cell surface remains stiff. The equatorial
      reduction of stiffness was compromised in cells with a mutation in the gene
      encoding the ZEN-4/kinesin-6 subunit of centralspindlin. Theoretical modeling
      showed that the absence of the equatorial reduction of stiffness could explain
      the arrest of furrow ingression in the mutant. By contrast, the equatorial
      reduction of stiffness was sufficient to generate a cleavage furrow even without
      the constriction force of the contractile ring. In this regime, the contractile
      ring had a supportive contribution to furrow ingression. We conclude that
      stiffness is reduced around the equator in a centralspindlin-dependent manner. In
      addition, computational modeling suggests that proper regulation of stiffness
      could be sufficient for cleavage furrow ingression.

PMID- 22359607
TI  - Transgenerational effects of parental larval diet on offspring development time,
      adult body size and pathogen resistance in Drosophila melanogaster.
AB  - Environmental conditions experienced by parents are increasingly recognized to
      affect offspring performance. We set out to investigate the effect of parental
      larval diet on offspring development time, adult body size and adult resistance
      to the bacterium Serratia marcescens in Drosophila melanogaster. Flies for the
      parental generation were raised on either poor or standard diet and then mated in
      the four possible sex-by-parental diet crosses. Females that were raised on poor
      food produced larger offspring than females that were raised on standard food.
      Furthermore, male progeny sired by fathers that were raised on poor food were
      larger than male progeny sired by males raised on standard food. Development
      times were shortest for offspring whose one parent (mother or the father) was
      raised on standard and the other parent on poor food and longest for offspring
      whose parents both were raised on poor food. No evidence for transgenerational
      effects of parental diet on offspring disease resistance was found. Although
      paternal effects have been previously demonstrated in D. melanogaster, no earlier
      studies have investigated male-mediated transgenerational effects of diet in this
      species. The results highlight the importance of not only considering the
      relative contribution each parental sex has on progeny performance but also the
      combined effects that the two sexes may have on offspring performance.

PMID- 22359609
TI  - A built-in mechanism to mitigate the spread of insect-resistance and herbicide
      tolerance transgenes into weedy rice populations.
AB  - BACKGROUND: The major challenge of cultivating genetically modified (GM) rice
      (Oryza sativa) at the commercial scale is to prevent the spread of transgenes
      from GM cultivated rice to its coexisting weedy rice (O. sativa f. spontanea).
      The strategic development of GM rice with a built-in control mechanism can
      mitigate transgene spread in weedy rice populations. METHODOLOGY/PRINCIPAL
      FINDINGS: An RNAi cassette suppressing the expression of the bentazon detoxifying
      enzyme CYP81A6 was constructed into the T-DNA which contained two tightly linked
      transgenes expressing the Bt insecticidal protein Cry1Ab and the glyphosate
      tolerant 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), respectively. GM
      rice plants developed from this T-DNA were resistant to lepidopteran pests and
      tolerant to glyphosate, but sensitive to bentazon. The application of bentazon of
      2000 mg/L at the rate of 40 mL/m(2), which is approximately the recommended dose
      for the field application to control common rice weeds, killed all F(2) plants
      containing the transgenes generated from the Crop-weed hybrids between a GM rice
      line (CGH-13) and two weedy rice strains (PI-63 and PI-1401).
      CONCLUSIONS/SIGNIFICANCE: Weedy rice plants containing transgenes from GM rice
      through gene flow can be selectively killed by the spray of bentazon when a non
      GM rice variety is cultivated alternately in a few-year interval. The built-in
      control mechanism in combination of cropping management is likely to mitigate the
      spread of transgenes into weedy rice populations.

PMID- 22359608
TI  - Transcriptome analysis and SNP development can resolve population differentiation
      of Streblospio benedicti, a developmentally dimorphic marine annelid.
AB  - Next-generation sequencing technology is now frequently being used to develop
      genomic tools for non-model organisms, which are generally important for
      advancing studies of evolutionary ecology. One such species, the marine annelid
      Streblospio benedicti, is an ideal system to study the evolutionary consequences
      of larval life history mode because the species displays a rare offspring
      dimorphism termed poecilogony, where females can produce either many small
      offspring or a few large ones. To further develop S. benedicti as a model system
      for studies of life history evolution, we apply 454 sequencing to characterize
      the transcriptome for embryos, larvae, and juveniles of this species, for which
      no genomic resources are currently available. Here we performed a de novo
      alignment of 336,715 reads generated by a quarter GS-FLX (Roche 454) run, which
      produced 7,222 contigs. We developed a novel approach for evaluating the site
      frequency spectrum across the transcriptome to identify potential signatures of
      selection. We also developed 84 novel single nucleotide polymorphism (SNP)
      markers for this species that are used to distinguish coastal populations of S.
      benedicti. We validated the SNPs by genotyping individuals of different
      developmental modes using the BeadXPress Golden Gate assay (Illumina). This
      allowed us to evaluate markers that may be associated with life-history mode.

PMID- 22359610
TI  - Glucose enhances leptin signaling through modulation of AMPK activity.
AB  - Leptin exerts its action by binding to and activating the long form of leptin
      receptors (LEPRb). LEPRb activates JAK2 that subsequently phosphorylates and
      activates STAT3. The JAK2/STAT3 pathway is required for leptin control of energy
      balance and body weight. Defects in leptin signaling lead to leptin resistance, a
      primary risk factor for obesity. Body weight is also regulated by nutrients,
      including glucose. Defects in glucose sensing also contribute to obesity. Here we
      report crosstalk between leptin and glucose. Glucose starvation blocked the
      ability of leptin to stimulate tyrosyl phosphorylation and activation of JAK2 and
      STAT3 in a variety of cell types. Glucose dose-dependently enhanced leptin
      signaling. In contrast, glucose did not enhance growth hormone-stimulated
      phosphorylation of JAK2 and STAT5. Glucose starvation or 2-deoxyglucose-induced
      inhibition of glycolysis activated AMPK and inhibited leptin signaling;
      pharmacological inhibition of AMPK restored the ability of leptin to stimulate
      STAT3 phosphorylation. Conversely, pharmacological activation of AMPK was
      sufficient to inhibit leptin signaling and to block the ability of glucose to
      enhance leptin signaling. These results suggest that glucose and/or its
      metabolites play a permissive role in leptin signaling, and that glucose enhances
      leptin sensitivity at least in part by attenuating the ability of AMPK to inhibit
      leptin signaling.

PMID- 22359611
TI  - Statin use and the presence of microalbuminuria. Results from the ERICABEL trial:
      a non-interventional epidemiological cohort study.
AB  - BACKGROUND: Microalbuminuria (MAU) is considered as a predictor or marker of
      cardiovascular and renal events. Statins are widely prescribed to reduce
      cardiovascular risk and to slow down progression of kidney disease. But statins
      may also generate tubular MAU. The current observational study evaluated the
      impact of statin use on the interpretation of MAU as a predictor or marker of
      cardiovascular or renal disease. METHODOLOGY/PRINCIPAL FINDINGS: We used cross
      sectional data of ERICABEL, a cohort with 1,076 hypertensive patients. MAU was
      defined as albuminuria >=20 mg/l. A propensity score was created to correct for
      "bias by indication" to receive a statin. As expected, subjects using statins vs.
      no statins had more cardiovascular risk factors, pointing to bias by indication.
      Statin users were more likely to have MAU (OR: 2.01, 95%CI: 1.34-3.01). The
      association between statin use and MAU remained significant after adjusting for
      the propensity to receive a statin based on cardiovascular risk factors (OR:
      1.82, 95%CI: 1.14-2.91). Next to statin use, only diabetes (OR: 1.92, 95%CI: 1.00
      3.66) and smoking (OR: 1.49, 95%CI: 0.99-2.26) were associated with MAU.
      CONCLUSIONS: Use of statins is independently associated with MAU, even after
      adjusting for bias by indication to receive a statin. In the hypothesis that this
      MAU is of tubular origin, statin use can result in incorrect labeling of subjects
      as having a predictor or marker of cardiovascular or renal risk. In addition,
      statin use affected the association of established cardiovascular risk factors
      with MAU, blurring the interpretation of multivariable analyses.

PMID- 22359613
TI  - Prescriptions of traditional Chinese medicine are specific to cancer types and
      adjustable to temperature changes.
AB  - Targeted cancer therapies, with specific molecular targets, ameliorate the side
      effect issue of radiation and chemotherapy and also point to the development of
      personalized medicine. Combination of drugs targeting multiple pathways of
      carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM)
      has been tailoring herbal mixtures for individualized healthcare for two thousand
      years. A systematic study of the patterns of TCM formulas and herbs prescribed to
      cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types
      of cancer in Taiwan in 2007, a year's worth of collection from the National
      Health Insurance reimbursement database (Taiwan). We found that a TCM cancer
      prescription consists on average of two formulas and four herbs. We show that the
      percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's
      law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a
      larger Zipf's exponent than those to malignant cancers. Furthermore, we show that
      TCM prescriptions, via weighted combination of formulas and herbs, are specific
      to not only the malignancy of neoplasms but also the sites of origins of
      malignant cancers. From the effects of formulas and natures of herbs that were
      heavily prescribed to cancers, that cancers are a 'warm and stagnant' syndrome in
      TCM can be proposed, suggesting anti-inflammatory regimens for better prevention
      and treatment of cancers. We show that TCM incorporated relevant formulas to the
      prescriptions to cancer patients with a secondary morbidity. We compared TCM
      prescriptions made in different seasons and identified temperatures as the
      environmental factor that correlates with changes in TCM prescriptions in Taiwan.
      Lung cancer patients were among the patients whose prescriptions were adjusted
      when temperatures drop. The findings of our study provide insight to TCM cancer
      treatment, helping dialogue between modern western medicine and TCM for better
      cancer care.

PMID- 22359612
TI  - The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and
      deactivation gating.
AB  - Human ether-a-go-go-related gene (hERG) K(+) channels have unusual gating
      kinetics. Characterised by slow activation/deactivation but rapid
      inactivation/recovery from inactivation, the unique gating kinetics underlie the
      central role hERG channels play in cardiac repolarisation. The slow activation
      and deactivation kinetics are regulated in part by the S4-S5 linker, which
      couples movement of the voltage sensor domain to opening of the activation gate
      at the distal end of the inner helix of the pore domain. It has also been
      suggested that cytosolic domains may interact with the S4-S5 linker to regulate
      activation and deactivation kinetics. Here, we show that the solution structure
      of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic
      helix. The effects of mutations at the majority of residues in the S4-S5 linker
      of hERG were consistent with the previously identified role in coupling voltage
      sensor movement to the activation gate. However, mutations to Ser543, Tyr545,
      Gly546 and Ala548 had more complex phenotypes indicating that these residues are
      involved in additional interactions. We propose a model in which the S4-S5
      linker, in addition to coupling VSD movement to the activation gate, also
      contributes to interactions that stabilise the closed state and a separate set of
      interactions that stabilise the open state. The S4-S5 linker therefore acts as a
      signal integrator and plays a crucial role in the slow deactivation kinetics of
      the channel.

PMID- 22359614
TI  - Adaptive models for gene networks.
AB  - Biological systems are often treated as time-invariant by computational models
      that use fixed parameter values. In this study, we demonstrate that the behavior
      of the p53-MDM2 gene network in individual cells can be tracked using adaptive
      filtering algorithms and the resulting time-variant models can approximate
      experimental measurements more accurately than time-invariant models. Adaptive
      models with time-variant parameters can help reduce modeling complexity and can
      more realistically represent biological systems.

PMID- 22359615
TI  - HIV-1 subtype D infections among Caucasians from Northwestern Poland-
      phylogenetic and clinical analysis.
AB  - BACKGROUND: HIV-1 subtype D infections, which are associated with a faster rate
      of progression and lymphocyte CD4 decline, cognitive deficit and higher
      mortality, have rarely been found in native Europeans. In Northwestern Poland,
      however, infections with this subtype had been identified. This study aimed to
      analyze the sequence and clinical data for patients with subtype D using
      molecular phylogeography and identify transmission clusters and ancestry, as well
      as drug resistance, baseline HIV tropism and antiretroviral treatment efficacy.
      METHODS: Phylogenetic analyses of local HIV-1 subtype D sequences were performed,
      with time to the most recent common ancestor inferred using bayesian modeling.
      Sequence and drug resistance data were linked with the clinical and
      epidemiological information. RESULTS: Subtype D was found in 24 non-immigrant
      Caucasian, heterosexually infected patients (75% of females, median age at
      diagnosis of 49.5 years; IQR: 29-56 years). Partial pol sequences clustered
      monophyletically with the clades of Ugandan origin and no evidence of
      transmission from other European countries was found. Time to the most common
      recent ancestor was 1989.24 (95% HPD: 1968.83-1994.46). Baseline drug resistance
      to nucleoside reverse transcriptase inhibitors was observed in 54.5% of cases
      (mutations: M41L, K103N, T215S/D) with evidence of clustering, no baseline
      integrase or protease resistance and infrequent non-R5 tropism (13.6%). Virologic
      failure was observed in 60% of cases and was associated with poor adherence
      (p<0.001) and subsequent development of drug resistance (p = 0.008, OR: 20
      (95%CI: 1.7-290). CONCLUSIONS: Local subtype D represented an independently
      transmitted network with probably single index case, high frequency of primary
      drug resistance and evidence of transmission clusters.

PMID- 22359616
TI  - Rapid detection of carbapenem resistance in Acinetobacter baumannii using matrix
      assisted laser desorption ionization-time of flight mass spectrometry.
AB  - Rapid detection of carbapenem-resistant Acinetobacter baumannii strains is
      critical and will benefit patient care by optimizing antibiotic therapies and
      preventing outbreaks. Herein we describe the development and successful
      application of a mass spectrometry profile generated by matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF) that utilized the imipenem
      antibiotic for the detection of carbapenem resistance in a large series of A.
      baumannii clinical isolates from France and Algeria. A total of 106 A. baumannii
      strains including 63 well-characterized carbapenemase-producing and 43 non
      carbapenemase-producing strains, as well as 43 control strains (7 carbapenem
      resistant and 36 carbapenem-sensitive strains) were studied. After an incubation
      of bacteria with imipenem for up to 4 h, the mixture was centrifuged and the
      supernatant analyzed by MALDI-TOF MS. The presence and absence of peaks
      representing imipenem and its natural metabolite was analyzed. The result was
      interpreted as positive for carbapenemase production if the specific peak for
      imipenem at 300.0 m/z disappeared during the incubation time and if the peak of
      the natural metabolite at 254.0 m/z increased as measured by the area under the
      curves leading to a ratio between the peak for imipenem and its metabolite being
      <0.5. This assay, which was applied to the large series of A. baumannii clinical
      isolates, showed a sensitivity of 100.0% and a specificity of 100.0%. Our study
      is the first to demonstrate that this quick and simple assay can be used as a
      routine tool as a point-of-care method for the identification of A. baumannii
      carbapenemase-producers in an effort to prevent outbreaks and the spread of
      uncontrollable superbugs.

PMID- 22359617
TI  - Collective motion of cells mediates segregation and pattern formation in co
      cultures.
AB  - Pattern formation by segregation of cell types is an important process during
      embryonic development. We show that an experimentally yet unexplored mechanism
      based on collective motility of segregating cells enhances the effects of known
      pattern formation mechanisms such as differential adhesion, mechanochemical
      interactions or cell migration directed by morphogens. To study in vitro cell
      segregation we use time-lapse videomicroscopy and quantitative analysis of the
      main features of the motion of individual cells or groups. Our observations have
      been extensive, typically involving the investigation of the development of
      patterns containing up to 200,000 cells. By either comparing keratocyte types
      with different collective motility characteristics or increasing cells'
      directional persistence by the inhibition of Rac1 GTP-ase we demonstrate that
      enhanced collective cell motility results in faster cell segregation leading to
      the formation of more extensive patterns. The growth of the characteristic scale
      of patterns generally follows an algebraic scaling law with exponent values up to
      0.74 in the presence of collective motion, compared to significantly smaller
      exponents in case of diffusive motion.

PMID- 22359618
TI  - Human alpha defensin 5 expression in the human kidney and urinary tract.
AB  - BACKGROUND: The mechanisms that maintain sterility in the urinary tract are
      incompletely understood. Recent studies have implicated the importance of
      antimicrobial peptides (AMP) in protecting the urinary tract from infection.
      Here, we characterize the expression and relevance of the AMP human alpha
      defensin 5 (HD5) in the human kidney and urinary tract in normal and infected
      subjects. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA isolated from human kidney,
      ureter, and bladder tissue, we performed quantitative real-time PCR to show that
      DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary
      tract. With pyelonephritis, DEFA5 expression significantly increased in the
      kidney. Using immunoblot analysis, HD5 production also increased with
      pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and
      ureter. In the kidney, HD5 was primarily produced in the distal nephron and
      collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely
      detected in non-infected human urine samples while mean urinary HD5 production
      increased with E.coli urinary tract infection. CONCLUSIONS/SIGNIFICANCE: DEFA5 is
      expressed throughout the urinary tract in non-infected subjects. Specifically,
      HD5 is expressed throughout the urothelium of the lower urinary tract and in the
      collecting tubules of the kidney. With infection, HD5 expression increases in the
      kidney and levels become detectable in the urine. To our knowledge, our findings
      represent the first to quantitate HD5 expression and production in the human
      kidney. Moreover, this is the first report to detect the presence of HD5 in
      infected urine samples. Our results suggest that HD5 may have an important role
      in maintaining urinary tract sterility.

PMID- 22359619
TI  - Hemagglutinin from the H5N1 virus activates Janus kinase 3 to dysregulate innate
      immunity.
AB  - Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in
      humans. There are no effective vaccines or antiviral therapies currently
      available to control fatal outbreaks due in part to the lack of understanding of
      virus-mediated immunopathology. In our study, we used hemagglutinin (HA) of H5N1
      virus to investigate the related signaling pathways and their relationship to
      dysregulated innate immune reaction. We found the HA of H5N1 avian influenza
      triggered an abnormal innate immune signalling in the pulmonary epithelial cells,
      through an unusual process involving activation of Janus kinase 3 (JAK3) that is
      exclusively associated with gammac chain and is essential for signaling via all
      gammac cytokine receptors. By using a selective JAK3 inhibitor and JAK3 knockout
      mice, we have, for the first time, demonstrated the ability to target active JAK3
      to counteract injury to the lungs and protect immunocytes from acute
      hypercytokinemia -induced destruction following the challenge of H5N1 HA in vitro
      and in vivo. On the basis of the present data, it appears that the efficacy of
      selective JAK3 inhibition is likely based on its ability to block multiple
      cytokines and protect against a superinflammatory response to pathogen-associated
      molecular patterns (PAMPs) attack. Our findings highlight the potential value of
      selective JAK3 inhibitor in treating the fatal immunopathology caused by H5N1
      challenge.

PMID- 22359620
TI  - Specific and sensitive hydrolysis probe-based real-time PCR detection of
      epidermal growth factor receptor variant III in oral squamous cell carcinoma.
AB  - BACKGROUND: The tumor-specific EGFR deletion mutant, EGFRvIII, is characterised
      by ligand-independent constitutive signalling. Tumors expressing EGFRvIII are
      resistant to current EGFR-targeted therapy. The frequency of EGFRvIII in head and
      neck squamous cell carcinoma (HNSCC) is disputed and may vary by specific sub
      site. The purpose of this study was to measure the occurrence of EGFRvIII
      mutations in a specific HNSCC subsite, oral squamous cell carcinoma (OSCC), using
      a novel real-time PCR assay. METHODOLOGY: Pre-treatment Formalin Fixed Paraffin
      Embedded (FFPE) cancer specimens from 50 OSCC patients were evaluated for the
      presence of EGFRvIII using a novel hydrolysis probe-based real-time PCR assay.
      EGFR protein expression in tumor samples was quantified using fluorescent
      immunohistochemistry (IHC) and AQUA(r) technology. PRINCIPAL FINDINGS: We
      detected EGFRvIII in a single OSCC patient in our cohort (2%). We confirmed the
      validity of our detection technique in an independent cohort of glioblastoma
      patients. We also compared the sensitivity and specificity of our novel real-time
      EGFRvIII detection assay to conventional RT-PCR and direct sequencing. Our assay
      can specifically detect EGFRvIII and can discriminate against wild-type EGFR in
      FFPE tumor samples. AQUAnalysis(r) revealed that the presence of EGFRvIII
      transcript is associated with very high EGFR protein expression (98(th)
      percentile). Contrary to previous reports, only 44% of OSCC over-expressed EGFR
      in our study. CONCLUSION AND SIGNIFICANCE: Our results suggest that the EGFRvIII
      mutation is rare in OSCC and corroborate previous reports of EGFRvIII expression
      only in tumors with extreme over-expression of EGFR. We conclude that EGFRvIII
      specific therapies may not be ideally suited as first-line treatment in OSCC.
      Furthermore, highly specific and sensitive methods, such as the real-time RT-PCR
      assay and AQUAnalysis(r) described here, will provide accurate assessment of EGFR
      mutation frequency and EGFR expression, and will facilitate the selection of
      optimal tailored therapies for OSCC patients.

PMID- 22359621
TI  - Reduced quantitative ultrasound bone mineral density in HIV-infected patients on
      antiretroviral therapy in Senegal.
AB  - BACKGROUND: Bone status in HIV-infected patients on antiretroviral treatment
      (ART) is poorly documented in resource-limited settings. We compared bone mineral
      density between HIV-infected patients and control subjects from Dakar, Senegal.
      METHODS: A total of 207 (134 women and 73 men) HIV-infected patients from an
      observational cohort in Dakar (ANRS 1215) and 207 age- and sex-matched controls
      from the general population were enrolled. Bone mineral density was assessed by
      quantitative ultrasound (QUS) at the calcaneus, an alternative to the reference
      method (i.e. dual X-absorptiometry), often not available in resource-limited
      countries. RESULTS: Mean age was 47.0 (+/-8.5) years. Patients had received ART
      for a median duration of 8.8 years; 45% received a protease inhibitor and 27%
      tenofovir; 84% had undetectable viral load. Patients had lower body mass index
      (BMI) than controls (23 versus 26 kg/m(2), P<0.001). In unadjusted analysis, QUS
      bone mineral density was lower in HIV-infected patients than in controls
      (difference: -0.36 standard deviation, 95% confidence interval (CI): -0.59;-0.12,
      P = 0.003). Adjusting for BMI, physical activity, smoking and calcium intake
      attenuated the difference (-0.27, CI: -0.53;-0.002, P = 0.05). Differences in BMI
      between patients and controls explained a third of the difference in QUS bone
      mineral density. Among patients, BMI was independently associated with QUS bone
      mineral density (P<0.001). An association between undetectable viral load and QUS
      bone density was also suggested (beta = 0.48, CI: 0.02;0.93; P = 0.04). No
      association between protease inhibitor or tenofovir use and QUS bone mineral
      density was found. CONCLUSION: Senegalese HIV-infected patients had reduced QUS
      bone mineral density in comparison with control subjects, in part related to
      their lower BMI. Further investigation is needed to clarify the clinical
      significance of these observations.

PMID- 22359622
TI  - A novel approach to determining violence risk in schizophrenia: developing a
      stepped strategy in 13,806 discharged patients.
AB  - Clinical guidelines recommend that violence risk be assessed in schizophrenia.
      Current approaches are resource-intensive as they employ detailed clinical
      assessments of dangerousness for most patients. An alternative approach would be
      to first screen out patients at very low risk of future violence prior to more
      costly and time-consuming assessments. In order to implement such a stepped
      strategy, we developed a simple tool to screen out individuals with schizophrenia
      at very low risk of violent offending. We merged high quality Swedish national
      registers containing information on psychiatric diagnoses, socio-demographic
      factors, and violent crime. A cohort of 13,806 individuals with hospital
      discharge diagnoses of schizophrenia was identified and followed for up to 33
      years for violent crime. Cox regression was used to determine risk factors for
      violent crime and construct the screening tool, the predictive validity of which
      was measured using four outcome statistics. The instrument was calibrated on
      6,903 participants and cross-validated using three independent replication
      samples of 2,301 participants each. Regression analyses resulted in a tool
      composed of five items: male sex, previous criminal conviction, young age at
      assessment, comorbid alcohol abuse, and comorbid drug abuse. At 5 years after
      discharge, the instrument had a negative predictive value of 0.99 (95% CI = 0.98
      0.99), meaning that very few individuals who the tool screened out (n = 2,359 out
      of original sample of 6,903) were subsequently convicted of a violent offence.
      Screening out patients who are at very low risk of violence prior to more
      detailed clinical assessment may assist the risk assessment process in
      schizophrenia.

PMID- 22359623
TI  - Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in
      non-thyroid cancer cells.
AB  - BACKGROUND: This study was designed to explore the therapeutic potential of
      suppressing MAP kinase and PI3K/Akt pathways and histone deacetylase (HDAC) to
      induce the expression of sodium/iodide symporter (NIS) and radioiodine uptake in
      non-thyroid cancer cells. METHODS: We tested the effects of the MEK inhibitor
      RDEA119, the Akt inhibitor perifosine, and the HDAC inhibitor SAHA on NIS
      expression in thirteen human cancer cell lines derived from melanoma, hepatic
      carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, and brain
      cancers. We also examined radioiodine uptake and histone acetylation at the NIS
      promoter in selected cells. RESULTS: Overall, the three inhibitors could induce
      NIS expression, to various extents, in melanoma and all the epithelial carcinoma
      derived cells but not in brain cancer-derived cells. SAHA was most effective and
      its effect could be significantly enhanced by RDEA119 and perifosine. The
      expression of NIS, at both mRNA and protein levels, was most robust in the
      melanoma cell M14, hepatic carcinoma cell HepG2, and the gastric carcinoma cell
      MKN-7 cell. Radioiodine uptake was correspondingly induced, accompanied by robust
      increase in histone acetylation at the NIS promoter, in these cells when treated
      with the three inhibitors. CONCLUSIONS: This is the first demonstration that
      simultaneously suppressing the MAP kinase and PI3K/Akt pathways and HDAC could
      induce robust NIS expression and radioiodine uptake in certain non-thyroid human
      cancer cells, providing novel therapeutic implications for adjunct radioiodine
      treatment of these cancers.

PMID- 22359624
TI  - Roles of major facilitator superfamily transporters in phosphate response in
      Drosophila.
AB  - The major facilitator superfamily (MFS) transporter Pho84 and the type III
      transporter Pho89 are responsible for metabolic effects of inorganic phosphate in
      yeast. While the Pho89 ortholog Pit1 was also shown to be involved in phosphate
      activated MAPK in mammalian cells, it is currently unknown, whether orthologs of
      Pho84 have a role in phosphate-sensing in metazoan species. We show here that the
      activation of MAPK by phosphate observed in mammals is conserved in Drosophila
      cells, and used this assay to characterize the roles of putative phosphate
      transporters. Surprisingly, while we found that RNAi-mediated knockdown of the
      fly Pho89 ortholog dPit had little effect on the activation of MAPK in Drosophila
      S2R+ cells by phosphate, two Pho84/SLC17A1-9 MFS orthologs (MFS10 and MFS13)
      specifically inhibited this response. Further, using a Xenopus oocyte assay, we
      show that MSF13 mediates uptake of [(33)P]-orthophosphate in a sodium-dependent
      fashion. Consistent with a role in phosphate physiology, MSF13 is expressed
      highest in the Drosophila crop, midgut, Malpighian tubule, and hindgut.
      Altogether, our findings provide the first evidence that Pho84 orthologs mediate
      cellular effects of phosphate in metazoan cells. Finally, while phosphate is
      essential for Drosophila larval development, loss of MFS13 activity is compatible
      with viability indicating redundancy at the levels of the transporters.

PMID- 22359625
TI  - Liver and muscle in morbid obesity: the interplay of fatty liver and insulin
      resistance.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a
      manifestation of overnutrition. The muscle is a central player in the adaptation
      to energy overload, and there is an association between fatty-muscle and -liver.
      We aimed to correlate muscle morphology, mitochondrial function and insulin
      signaling with NAFLD severity in morbid obese patients. METHODS: Liver and
      deltoid muscle biopsies were collected during bariatric surgery in NAFLD
      patients. NAFLD Activity Score and Younossi's classification for nonalcoholic
      steatohepatitis (NASH) were applied to liver histology. Muscle evaluation
      included morphology studies, respiratory chain complex I to IV enzyme assays, and
      analysis of the insulin signaling cascade. A healthy lean control group was
      included for muscle morphology and mitochondrial function analyses. RESULTS:
      Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular
      lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001),
      progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010).
      There was a trend to an association between IMCL and decreased Akt
      phosphorylation (p = 0.059), despite no association with insulin resistance. In
      turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated
      with decreased Akt phosphoryation. Citrate synthase activity was lower in obese
      patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities
      were higher, compared with controls. Finally, in obese patients, complex I
      activity increased with progressive steatosis (p = 0.049) and with a trend with
      fibrosis severity (p = 0.056). CONCLUSIONS: In morbid obese patients, presence of
      IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction
      does not appear to be a major driving force contributing to muscle fat
      accumulation, insulin resistance or liver disease. Importantly, insulin
      resistance in muscle might occur at a late point in the insulin signaling cascade
      and be associated with IMCL and NAFLD severity.

PMID- 22359626
TI  - Genome-wide RNAi screen in IFN-gamma-treated human macrophages identifies genes
      mediating resistance to the intracellular pathogen Francisella tularensis.
AB  - Interferon-gamma (IFN-gamma) inhibits intracellular replication of Francisella
      tularensis in human monocyte-derived macrophages (HMDM) and in mice, but the
      mechanisms of this protective effect are poorly characterized. We used genome
      wide RNA interference (RNAi) screening in the human macrophage cell line THP-1 to
      identify genes that mediate the beneficial effects of IFN-gamma on F. tularensis
      infection. A primary screen identified ~200 replicated candidate genes. These
      were prioritized according to mRNA expression in IFN-gamma-primed and F.
      tularensis-challenged macrophages. A panel of 20 top hits was further assessed by
      re-testing using individual shRNAs or siRNAs in THP-1 cells, HMDMs and primary
      human lung macrophages. Six of eight validated genes tested were also found to
      confer resistance to Listeria monocytogenes infection, suggesting a broadly
      shared host gene program for intracellular pathogens. The F. tularensis-validated
      hits included 'druggable' targets such as TNFRSF9, which encodes CD137. Treating
      HMDM with a blocking antibody to CD137 confirmed a beneficial role of CD137 in
      macrophage clearance of F. tularensis. These studies reveal a number of important
      mediators of IFN-gamma activated host defense against intracellular pathogens,
      and implicate CD137 as a potential therapeutic target and regulator of macrophage
      interactions with Francisella tularensis.

PMID- 22359628
TI  - A policy-driven large scale ecological restoration: quantifying ecosystem
      services changes in the Loess Plateau of China.
AB  - As one of the key tools for regulating human-ecosystem relations, environmental
      conservation policies can promote ecological rehabilitation across a variety of
      spatiotemporal scales. However, quantifying the ecological effects of such
      policies at the regional level is difficult. A case study was conducted at the
      regional level in the ecologically vulnerable region of the Loess Plateau, China,
      through the use of several methods including the Universal Soil Loss Equation
      (USLE), hydrological modeling and multivariate analysis. An assessment of the
      changes over the period of 2000-2008 in four key ecosystem services was
      undertaken to determine the effects of the Chinese government's ecological
      rehabilitation initiatives implemented in 1999. These ecosystem services included
      water regulation, soil conservation, carbon sequestration and grain production.
      Significant conversions of farmland to woodland and grassland were found to have
      resulted in enhanced soil conservation and carbon sequestration, but decreased
      regional water yield under a warming and drying climate trend. The total grain
      production increased in spite of a significant decline in farmland acreage. These
      trends have been attributed to the strong socioeconomic incentives embedded in
      the ecological rehabilitation policy. Although some positive policy results have
      been achieved over the last decade, large uncertainty remains regarding long-term
      policy effects on the sustainability of ecological rehabilitation performance and
      ecosystem service enhancement. To reduce such uncertainty, this study calls for
      an adaptive management approach to regional ecological rehabilitation policy to
      be adopted, with a focus on the dynamic interactions between people and their
      environments in a changing world.

PMID- 22359627
TI  - Site specific effects of zoledronic acid during tibial and mandibular fracture
      repair.
AB  - Numerous factors can affect skeletal regeneration, including the extent of bone
      injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates
      are anticatabolic agents that have been widely used to treat a variety of
      metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate
      (N-BP), is the most potent bisphosphonate among the clinically approved
      bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have
      been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis
      does not occur in long bones. The aim of this study was to compare the effects of
      zoledronate on long bone and cranial bone regeneration using a previously
      established model of non-stabilized tibial fractures and a new model of
      mandibular fracture repair. Contrary to tibial fractures, which heal mainly
      through endochondral ossification, mandibular fractures healed via endochondral
      and intramembranous ossification with a lesser degree of endochondral
      ossification compared to tibial fractures. In the tibia, ZA reduced callus and
      cartilage formation during the early stages of repair. In parallel, we found a
      delay in cartilage hypertrophy and a decrease in angiogenesis during the soft
      callus phase of repair. During later stages of repair, ZA delayed callus,
      cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and
      bone remodeling in correlation with a decrease in osteoclast number during the
      soft and hard callus phases of repair. These results reveal a more profound
      impact of ZA on cartilage and bone remodeling in the mandible compared to the
      tibia. This may predispose mandible bone to adverse effects of ZA in disease
      conditions. These results also imply that therapeutic effects of ZA may need to
      be optimized using time and dose-specific treatments in cranial versus long
      bones.

PMID- 22359629
TI  - Deciphering the preference and predicting the viability of circular permutations
      in proteins.
AB  - Circular permutation (CP) refers to situations in which the termini of a protein
      are relocated to other positions in the structure. CP occurs naturally and has
      been artificially created to study protein function, stability and folding.
      Recently CP is increasingly applied to engineer enzyme structure and function,
      and to create bifunctional fusion proteins unachievable by tandem fusion. CP is a
      complicated and expensive technique. An intrinsic difficulty in its application
      lies in the fact that not every position in a protein is amenable for creating a
      viable permutant. To examine the preferences of CP and develop CP viability
      prediction methods, we carried out comprehensive analyses of the sequence,
      structural, and dynamical properties of known CP sites using a variety of
      statistics and simulation methods, such as the bootstrap aggregating, permutation
      test and molecular dynamics simulations. CP particularly favors Gly, Pro, Asp and
      Asn. Positions preferred by CP lie within coils, loops, turns, and at residues
      that are exposed to solvent, weakly hydrogen-bonded, environmentally unpacked, or
      flexible. Disfavored positions include Cys, bulky hydrophobic residues, and
      residues located within helices or near the protein's core. These results
      fostered the development of an effective viable CP site prediction system, which
      combined four machine learning methods, e.g., artificial neural networks, the
      support vector machine, a random forest, and a hierarchical feature integration
      procedure developed in this work. As assessed by using the hydrofolate reductase
      dataset as the independent evaluation dataset, this prediction system achieved an
      AUC of 0.9. Large-scale predictions have been performed for nine thousand
      representative protein structures; several new potential applications of CP were
      thus identified. Many unreported preferences of CP are revealed in this study.
      The developed system is the best CP viability prediction method currently
      available. This work will facilitate the application of CP in research and
      biotechnology.

PMID- 22359630
TI  - Decreased circulating endothelial progenitor cell levels and function in patients
      with nonalcoholic fatty liver disease.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is associated with advanced
      atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence
      suggests that injured endothelial monolayer is regenerated by circulating bone
      marrow derived-endothelial progenitor cells (EPCs), and levels of circulating
      EPCs reflect vascular repair capacity. However, the relation between NAFLD and
      EPC remains unclear. Here, we tested the hypothesis that patients with
      nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial
      progenitor cell (EPC) levels and attenuated EPC function. METHODS AND RESULTS: A
      total of 312 consecutive patients undergoing elective coronary angiography
      because of suspected coronary artery disease were screened and received
      examinations of abdominal ultrasonography between July 2009 and November 2010.
      Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and
      sex-matched controls without NAFLD were enrolled. Flow cytometry with
      quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and
      CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating
      EPC numbers. The adhesive function, and migration, and tube formation capacities
      of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD
      had a significantly higher incidence of metabolic syndrome, previous myocardial
      infarction, hyperuricemia, and higher waist circumference, body mass index,
      fasting glucose and triglyceride levels. In addition, patients with NAFLD had
      significantly decreased circulating EPC levels (all P<0.05), attenuated EPC
      functions, and enhanced systemic inflammation compared to controls. Multivariate
      logistic regression analysis showed that circulating EPC level (CD34(+)KDR(+)
      [cells/10(5) events]) was an independent reverse predictor of NAFLD (Odds ratio:
      0.78; 95% confidence interval: 0.69-0.89, P<0.001). CONCLUSIONS: NAFLD patients
      have decreased circulating EPC numbers and functions than those without NAFLD,
      which may be one of the mechanisms to explain atherosclerotic disease progression
      and enhanced cardiovascular risk in patients with NAFLD.

PMID- 22359631
TI  - Treatment- and population-dependent activity patterns of behavioral and
      expression QTLs.
AB  - Genetic control of gene expression and higher-order phenotypes is almost
      invariably dependent on environment and experimental conditions. We use two
      families of recombinant inbred strains of mice (LXS and BXD) to study treatment-
      and genotype-dependent control of hippocampal gene expression and behavioral
      phenotypes. We analyzed responses to all combinations of two experimental
      perturbations, ethanol and restraint stress, in both families, allowing for
      comparisons across 8 combinations of treatment and population. We introduce the
      concept of QTL activity patterns to characterize how associations between genomic
      loci and traits vary across treatments. We identified several significant
      behavioral QTLs and many expression QTLs (eQTLs). The behavioral QTLs are highly
      dependent on treatment and population. We classified eQTLs into three groups: cis
      eQTLs (expression variation that maps to within 5 Mb of the cognate gene),
      syntenic trans-eQTLs (the gene and the QTL are on the same chromosome but not
      within 5 Mb), and non-syntenic trans-eQTLs (the gene and the QTL are on different
      chromosomes). We found that most non-syntenic trans-eQTLs were treatment-specific
      whereas both classes of syntenic eQTLs were more conserved across treatments. We
      also found there was a correlation between regions along the genome enriched for
      eQTLs and SNPs that were conserved across the LXS and BXD families. Genes with
      eQTLs that co-localized with the behavioral QTLs and displayed similar QTL
      activity patterns were identified as potential candidate genes associated with
      the phenotypes, yielding identification of novel genes as well as genes that have
      been previously associated with responses to ethanol.

PMID- 22359632
TI  - Effect of biocontrol agent Pseudomonas fluorescens 2P24 on soil fungal community
      in cucumber rhizosphere using T-RFLP and DGGE.
AB  - Fungi and fungal community play important roles in the soil ecosystem, and the
      diversity of fungal community could act as natural antagonists of various plant
      pathogens. Biological control is a promising method to protect plants as chemical
      pesticides may cause environment pollution. Pseudomonas fluorescens 2P24 had
      strong inhibitory on Rastonia solanacearum, Fusarium oxysporum and Rhizoctonia
      solani, etc., and was isolated from the wheat rhizosphere take-all decline soils
      in Shandong province, China. However, its potential effect on soil fungal
      community was still unknown. In this study, the gfp-labeled P. fluorescens 2P24
      was inoculated into cucumber rhizosphere, and the survival of 2P24 was monitored
      weekly. The amount decreased from 10(8) to 10(5) CFU/g dry soils. The effect of
      2P24 on soil fungal community in cucumber rhizosphere was investigated using T
      RFLP and DGGE. In T-RFLP analysis, principle component analysis showed that the
      soil fungal community was greatly influenced at first, digested with restriction
      enzyme Hinf I and Taq I. However, there was little difference as digested by
      different enzymes. DGGE results demonstrated that the soil fungal community was
      greatly shocked at the beginning, but it recovered slowly with the decline of P.
      fluorescens 2P24. Four weeks later, there was little difference between the
      treatment and control. Generally speaking, the effect of P. fluorescens 2P24 on
      soil fungal community in cucumber rhizosphere was just transient.

PMID- 22359633
TI  - L-cysteine administration attenuates pancreatic fibrosis induced by TNBS in rats
      by inhibiting the activation of pancreatic stellate cell.
AB  - BACKGROUND AND AIMS: Recent studies have shown that activated pancreatic stellate
      cells (PSCs) play a major role in pancreatic fibrogenesis. We aimed to study the
      effect of L-cysteine administration on fibrosis in chronic pancreatitis (CP)
      induced by trinitrobenzene sulfonic acid (TNBS) in rats and on the function of
      cultured PSCs. METHODS: CP was induced by TNBS infusion into rat pancreatic
      ducts. L-cysteine was administrated for the duration of the experiment.
      Histological analysis and the contents of hydroxyproline were used to evaluate
      pancreatic damage and fibrosis. Immunohistochemical analysis of alpha-SMA in the
      pancreas was performed to detect the activation of PSCs in vivo. The collagen
      deposition related proteins and cytokines were determined by western blot
      analysis. DNA synthesis of cultured PSCs was evaluated by BrdU incorporation. We
      also evaluated the effect of L-cysteine on the cell cycle and cell activation by
      flow cytometry and immunocytochemistry. The expression of PDGFRbeta, TGFbetaRII,
      collagen 1alpha1 and alpha-SMA of PSCs treated with different concentrations of L
      cysteine was determined by western blot. Parameters of oxidant stress were
      evaluated in vitro and in vivo. Nrf2, NQO1, HO-1, IL-1beta expression were
      evaluated in pancreas tissues by qRT-PCR. RESULTS: The inhibition of pancreatic
      fibrosis by L-cysteine was confirmed by histological observation and
      hydroxyproline assay. alpha-SMA, TIMP1, IL-1beta and TGF-beta1 production
      decreased compared with the untreated group along with an increase in MMP2
      production. L-cysteine suppressed the proliferation and extracellular matrix
      production of PSCs through down-regulating of PDGFRbeta and TGFbetaRII.
      Concentrations of MDA+4-HNE were decreased by L-cysteine administration along
      with an increase in GSH levels both in tissues and cells. In addition, L-cysteine
      increased the mRNA expression of Nrf2, NQO1 and HO-1 and reduced the expression
      of IL-1beta in L-cysteine treated group when compared with control group.
      CONCLUSION: L-cysteine treatment attenuated pancreatic fibrosis in chronic
      pancreatitis in rats.

PMID- 22359634
TI  - Increased prevalence of metabolic syndrome in patients with acne inversa.
AB  - BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a
      common chronic inflammatory skin disease, localized in the axillary, inguinal and
      perianal skin areas that causes painful, fistulating sinuses with malodorous
      purulence and scars. Several chronic inflammatory diseases are associated with
      the metabolic syndrome and its consequences including arteriosclerosis, coronary
      heart disease, myocardial infraction, and stroke. So far, the association of AI
      with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS:
      A hospital-based case-control study in 80 AI patients and 100 age- and sex
      matched control participants was carried out. The prevalence of central obesity
      (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL
      cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI
      patients was significantly higher than in controls. Furthermore, the metabolic
      syndrome, previously defined as the presence of at least three of the five
      alterations listed above, was more common in those patients compared to controls
      (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96;
      P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic
      alterations than controls with metabolic syndrome. Interestingly, there was no
      correlation between the severity or duration of the disease and the levels of
      respective parameters or the number of criteria defining the metabolic syndrome.
      Rather, the metabolic syndrome was observed in a disproportionately high
      percentage of young AI patients. CONCLUSIONS: This study shows for the first time
      that AI patients have a high prevalence of the metabolic syndrome and all of its
      criteria. It further suggests that the inflammation present in AI patients does
      not have a major impact on the development of metabolic alterations. Instead,
      evidence is given for a role of metabolic alterations in the development of AI.
      We recommend monitoring of AI patients in order to correct their modifiable
      cardiovascular risk factors.

PMID- 22359635
TI  - Maternal health status correlates with nest success of leatherback sea turtles
      (Dermochelys coriacea) from Florida.
AB  - Of the seven sea turtle species, the critically endangered leatherback sea turtle
      (Dermochelys coriacea) exhibits the lowest and most variable nest success (i.e.,
      hatching success and emergence success) for reasons that remain largely unknown.
      In an attempt to identify or rule out causes of low reproductive success in this
      species, we established the largest sample size (n = 60-70 for most values) of
      baseline blood parameters (protein electrophoresis, hematology, plasma
      biochemistry) for this species to date. Hematologic, protein electrophoretic and
      biochemical values are important tools that can provide information regarding the
      physiological condition of an individual and population health as a whole. It has
      been proposed that the health of nesting individuals affects their reproductive
      output. In order to establish correlations with low reproductive success in
      leatherback sea turtles from Florida, we compared maternal health indices to
      hatching success and emergence success of their nests. As expected, hatching
      success (median = 57.4%) and emergence success (median = 49.1%) in Floridian
      leatherbacks were low during the study period (2007-2008 nesting seasons), a
      trend common in most nesting leatherback populations (average global hatching
      success = ~50%). One protein electrophoretic value (gamma globulin protein) and
      one hematologic value (red blood cell count) significantly correlated with
      hatching success and emergence success. Several maternal biochemical parameters
      correlated with hatching success and/or emergence success including alkaline
      phosphatase activity, blood urea nitrogen, calcium, calcium:phosphorus ratio,
      carbon dioxide, cholesterol, creatinine, and phosphorus. Our results suggest that
      in leatherbacks, physiological parameters correlate with hatching success and
      emergence success of their nests. We conclude that long-term and comparative
      studies are needed to determine if certain individuals produce nests with lower
      hatching success and emergence success than others, and if those individuals with
      evidence of chronic suboptimal health have lower reproductive success.

PMID- 22359636
TI  - ATP-independent cooperative binding of yeast Isw1a to bare and nucleosomal DNA.
AB  - Among chromatin remodeling factors, the ISWI family displays a nucleosome
      enhanced ATPase activity coupled to DNA translocation. While these enzymes are
      known to bind to DNA, their activity has not been fully characterized. Here we
      use TEM imaging and single molecule manipulation to investigate the interaction
      between DNA and yeast Isw1a. We show that Isw1a displays a highly cooperative ATP
      independent binding to and bridging between DNA segments. Under appropriate
      tension, rare single nucleation events can sometimes be observed and loop DNA
      with a regular step. These nucleation events are often followed by binding of
      successive complexes bridging between nearby DNA segments in a zipper-like
      fashion, as confirmed by TEM observations. On nucleosomal substrates, we show
      that the specific ATP-dependent remodeling activity occurs in the context of
      cooperative Isw1a complexes bridging extranucleosomal DNA. Our results are
      interpreted in the context of the recently published partial structure of Isw1a
      and support its acting as a "protein ruler" (with possibly more than one tick).

PMID- 22359637
TI  - Nonadhesive culture system as a model of rapid sphere formation with cancer stem
      cell properties.
AB  - BACKGROUND: Cancer stem cells (CSCs) play an important role in tumor initiation,
      progression, and metastasis and are responsible for high therapeutic failure
      rates. Identification and characterization of CSC are crucial for facilitating
      the monitoring, therapy, or prevention of cancer. Great efforts have been paid to
      develop a more effective methodology. Nevertheless, the ideal model for CSC
      research is still evolving. In this study, we created a nonadhesive culture
      system to enrich CSCs from human oral squamous cell carcinoma cell lines with
      sphere formation and to characterize their CSC properties further. METHODS: A
      nonadhesive culture system was designed to generate spheres from the SAS and OECM
      1 cell lines. A subsequent investigation of their CSC properties, including
      stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor
      initiation capacity in vivo, was also performed. RESULTS: Spheres were formed
      cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved
      that these spheres expressed putative stem cell markers and exhibited
      chemoradiotherapeutic resistance, in addition to tumor-initiating and self
      renewal capabilities. CONCLUSIONS: Using this nonadhesive culture system, we
      successfully established a rapid and cost-effective model that exhibits the
      characteristics of CSCs and can be used in cancer research.

PMID- 22359638
TI  - Surveillance of Schistosoma japonicum infection in domestic ruminants in the
      Dongting Lake region, Hunan province, China.
AB  - BACKGROUND: Schistosomiasis japonica is prevalent in Asian countries and it
      remains a major public health problem in China. The major endemic foci are the
      marsh and lake regions of southern China, particularly the Dongting Lake region
      bordering Hunan and Hubei provinces, and the Poyang Lake region in Jiangxi
      province. Domestic ruminants, especially bovines, have long been considered to
      play a major role in the transmission of Schistosoma japonicum to humans. METHODS
      AND FINDINGS: A miracidial hatching technique was used to investigate the
      prevalence of S. japonicum infections in domestic ruminants and field feces
      collected from two towns located to the south and east of Dongting Lake, Hunan
      province, between 2005 and 2010. The overall prevalence of infection was not
      significantly reduced from 4.93% in 2005 to 3.64% in 2008, after which it was
      maintained at this level. Bovines comprised 23.5-58.2% of the total infected
      ruminants, while goats comprised 41.8-76.5%. Infection rates in cattle and goats
      were significantly higher than those found in buffalo in most study years. The
      prevalence in buffalo younger than three years was significantly higher than that
      in those aged over three years. All the positive field samples of feces were
      derived from bovines in Nandashan. In Matang Town, 61.22% of the positive field
      feces were from bovines, while the rest were from goats. The positive rates for
      field feces were approximately the same in April and November/October.
      CONCLUSIONS: The present study found that bovines and goats are major sources of
      S. japonicum infection in the Dongting lake region and there was age-related
      resistance in buffalo. Both bovines and goats should be treated equally when
      controlling S. japonicum infections in the Dongting lake region. It is essential
      to conduct an additional mass treatment in late March or early April, in addition
      to the original treatment scheme.

PMID- 22359639
TI  - The neuronal correlates of digits backward are revealed by voxel-based
      morphometry and resting-state functional connectivity analyses.
AB  - Digits backward (DB) is a widely used neuropsychological measure that is believed
      to be a simple and effective index of the capacity of the verbal working memory.
      However, its neural correlates remain elusive. The aim of this study is to
      investigate the neural correlates of DB in 299 healthy young adults by combining
      voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC)
      analyses. The VBM analysis showed positive correlations between the DB scores and
      the gray matter volumes in the right anterior superior temporal gyrus (STG), the
      right posterior STG, the left inferior frontal gyrus and the left Rolandic
      operculum, which are four critical areas in the auditory phonological loop of the
      verbal working memory. Voxel-based correlation analysis was then performed
      between the positive rsFCs of these four clusters and the DB scores. We found
      that the DB scores were positively correlated with the rsFCs within the salience
      network (SN), that is, between the right anterior STG, the dorsal anterior
      cingulate cortex and the right fronto-insular cortex. We also found that the DB
      scores were negatively correlated with the rsFC within an anti-correlation
      network of the SN, between the right posterior STG and the left posterior insula.
      Our findings suggest that DB performance is related to the structural and
      functional organizations of the brain areas that are involved in the auditory
      phonological loop and the SN.

PMID- 22359640
TI  - Social, environmental and psychological factors associated with objective
      physical activity levels in the over 65s.
AB  - OBJECTIVE: To assess physical activity levels objectively using accelerometers in
      community dwelling over 65 s and to examine associations with health, social,
      environmental and psychological factors. DESIGN: Cross sectional survey. SETTING:
      17 general practices in Scotland, United Kingdom. PARTICIPANTS: Random sampling
      of over 65 s registered with the practices in four strata young-old (65-80
      years), old-old (over 80 years), more affluent and less affluent groups. MAIN
      OUTCOME MEASURES: Accelerometry counts of activity per day. Associations between
      activity and Theory of Planned Behaviour variables, the physical environment,
      health, wellbeing and demographic variables were examined with multiple
      regression analysis and multilevel modelling. RESULTS: 547 older people (mean
      (SD) age 79(8) years, 54% female) were analysed representing 94% of those
      surveyed. Accelerometry counts were highest in the affluent younger group,
      followed by the deprived younger group, with lowest levels in the deprived over
      80 s group. Multiple regression analysis showed that lower age, higher perceived
      behavioural control, the physical function subscale of SF-36, and having someone
      nearby to turn to were all independently associated with higher physical activity
      levels (R(2) = 0.32). In addition, hours of sunshine were independently
      significantly associated with greater physical activity in a multilevel model.
      CONCLUSIONS: Other than age and hours of sunlight, the variables identified are
      modifiable, and provide a strong basis for the future development of novel
      multidimensional interventions aimed at increasing activity participation in
      later life.

PMID- 22359642
TI  - The effects of low levels of dystrophin on mouse muscle function and pathology.
AB  - Duchenne muscular dystrophy (DMD) is a severe progressive muscular disorder
      caused by reading frame disrupting mutations in the DMD gene, preventing the
      synthesis of functional dystrophin. As dystrophin provides muscle fiber stability
      during contractions, dystrophin negative fibers are prone to exercise-induced
      damage. Upon exhaustion of the regenerative capacity, fibers will be replaced by
      fibrotic and fat tissue resulting in a progressive loss of function eventually
      leading to death in the early thirties. With several promising approaches for the
      treatment of DMD aiming at dystrophin restoration in clinical trials, there is an
      increasing need to determine more precisely which dystrophin levels are
      sufficient to restore muscle fiber integrity, protect against muscle damage and
      improve muscle function.To address this we generated a new mouse model (mdx
      Xist(Deltahs)) with varying, low dystrophin levels (3-47%, mean 22.7%, stdev
      12.1, n = 24) due to skewed X-inactivation. Longitudinal sections revealed that
      within individual fibers, some nuclei did and some did not express dystrophin,
      resulting in a random, mosaic pattern of dystrophin expression within fibers.Mdx
      Xist(Deltahs), mdx and wild type females underwent a 12 week functional test
      regime consisting of different tests to assess muscle function at base line, or
      after chronic treadmill running exercise. Overall, mdx-Xist(Deltahs) mice with 3
      14% dystrophin outperformed mdx mice in the functional tests. Improved
      histopathology was observed in mice with 15-29% dystrophin and these levels also
      resulted in normalized expression of pro-inflammatory biomarker genes, while for
      other parameters >30% of dystrophin was needed. Chronic exercise clearly worsened
      pathology, which needed dystrophin levels >20% for protection. Based on these
      findings, we conclude that while even dystrophin levels below 15% can improve
      pathology and performance, levels of >20% are needed to fully protect muscle
      fibers from exercise-induced damage.

PMID- 22359641
TI  - Widespread mRNA association with cytoskeletal motor proteins and identification
      and dynamics of myosin-associated mRNAs in S. cerevisiae.
AB  - Programmed mRNA localization to specific subcellular compartments for localized
      translation is a fundamental mechanism of post-transcriptional regulation that
      affects many, and possibly all, mRNAs in eukaryotes. We describe here a
      systematic approach to identify the RNA cargoes associated with the cytoskeletal
      motor proteins of Saccharomyces cerevisiae in combination with live-cell 3D super
      localization microscopy of endogenously tagged mRNAs. Our analysis identified
      widespread association of mRNAs with cytoskeletal motor proteins, including
      association of Myo3 with mRNAs encoding key regulators of actin branching and
      endocytosis such as WASP and WIP. Using conventional fluorescence microscopy and
      expression of MS2-tagged mRNAs from endogenous loci, we observed a strong bias
      for actin patch nucleator mRNAs to localize to the cell cortex and the actin
      patch in a Myo3- and F-actin dependent manner. Use of a double-helix point spread
      function (DH-PSF) microscope allowed super-localization measurements of single
      mRNPs at a spatial precision of 25 nm in x and y and 50 nm in z in live cells
      with 50 ms exposure times, allowing quantitative profiling of mRNP dynamics. The
      actin patch mRNA exhibited distinct and characteristic diffusion coefficients
      when compared to a control mRNA. In addition, disruption of F-actin significantly
      expanded the 3D confinement radius of an actin patch nucleator mRNA, providing a
      quantitative assessment of the contribution of the actin cytoskeleton to mRNP
      dynamic localization. Our results provide evidence for specific association of
      mRNAs with cytoskeletal motor proteins in yeast, suggest that different mRNPs
      have distinct and characteristic dynamics, and lend insight into the mechanism of
      actin patch nucleator mRNA localization to actin patches.

PMID- 22359643
TI  - Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human
      malaria, Plasmodium falciparum.
AB  - BACKGROUND: Plasmodium falciparum, the causative agent of human malaria,
      expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a
      free amino acid pool used by the intraerythrocytic stage of the parasite for
      proteins synthesis, growth and development. These exopeptidases are potential
      targets for the development of a new class of anti-malaria drugs.
      METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of
      recombinant forms of these two malaria aminopeptidases we used a new library
      consisting of 61 fluorogenic substrates derived both from natural and unnatural
      amino acids. We obtained a detailed substrate fingerprint for recombinant forms
      of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance,
      capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP
      has narrower substrate specificity and preferentially cleaves bulky, hydrophobic
      amino acids. The substrate library was also exploited to profile the activity of
      the native aminopeptidases in soluble cell lysates of P. falciparum malaria.
      CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are
      responsible for majority of the aminopeptidase activity in these extracts. These
      studies provide specific substrate and mechanistic information important for
      understanding the function of these aminopeptidases and could be exploited in the
      design of new inhibitors to specifically target these for anti-malaria treatment.

PMID- 22359644
TI  - IRE1/bZIP60-mediated unfolded protein response plays distinct roles in plant
      immunity and abiotic stress responses.
AB  - Endoplasmic reticulum (ER)-mediated protein secretion and quality control have
      been shown to play an important role in immune responses in both animals and
      plants. In mammals, the ER membrane-located IRE1 kinase/endoribonuclease, a key
      regulator of unfolded protein response (UPR), is required for plasma cell
      development to accommodate massive secretion of immunoglobulins. Plant cells can
      secrete the so-called pathogenesis-related (PR) proteins with antimicrobial
      activities upon pathogen challenge. However, whether IRE1 plays any role in plant
      immunity is not known. Arabidopsis thaliana has two copies of IRE1, IRE1a and
      IRE1b. Here, we show that both IRE1a and IRE1b are transcriptionally induced
      during chemically-induced ER stress, bacterial pathogen infection and treatment
      with the immune signal salicylic acid (SA). However, we found that IRE1a plays a
      predominant role in the secretion of PR proteins upon SA treatment. Consequently,
      the ire1a mutant plants show enhanced susceptibility to a bacterial pathogen and
      are deficient in establishing systemic acquired resistance (SAR), whereas ire1b
      is unaffected in these responses. We further demonstrate that the immune
      deficiency in ire1a is due to a defect in SA- and pathogen-triggered, IRE1
      mediated cytoplasmic splicing of the bZIP60 mRNA, which encodes a transcription
      factor involved in the expression of UPR-responsive genes. Consistently, IRE1a is
      preferentially required for bZIP60 splicing upon pathogen infection, while IRE1b
      plays a major role in bZIP60 processing upon Tunicamycin (Tm)-induced stress. We
      also show that SA-dependent induction of UPR-responsive genes is altered in the
      bzip60 mutant resulting in a moderate susceptibility to a bacterial pathogen.
      These results indicate that the IRE1/bZIP60 branch of UPR is a part of the plant
      response to pathogens for which the two Arabidopsis IRE1 isoforms play only
      partially overlapping roles and that IRE1 has both bZIP60-dependent and bZIP60
      independent functions in plant immunity.

PMID- 22359645
TI  - Lack of renal 11 beta-hydroxysteroid dehydrogenase type 2 at birth, a targeted
      temporal window for neonatal glucocorticoid action in human and mice.
AB  - BACKGROUND: Glucocorticoid hormones play a major role in fetal organ maturation.
      Yet, excessive glucocorticoid exposure in utero can result in a variety of
      detrimental effects, such as growth retardation and increased susceptibility to
      the development of hypertension. To protect the fetus, maternal glucocorticoids
      are metabolized into inactive compounds by placental 11beta-hydroxysteroid
      dehydrogenase type2 (11betaHSD2). This enzyme is also expressed in the kidney,
      where it prevents illicit occupation of the mineralocorticoid receptor by
      glucocorticoids. We investigated the role of renal 11betaHSD2 in the control of
      neonatal glucocorticoid metabolism in the human and mouse. METHODS: Cortisol (F)
      and cortisone (E) concentrations were measured in maternal plasma, umbilical cord
      blood and human newborn urine using HPLC. 11betaHSD2 activity was indirectly
      assessed by comparing the F/E ratio between maternal and neonatal plasma
      (placental activity) and between plasma and urine in newborns (renal activity).
      Direct measurement of renal 11betaHSD2 activity was subsequently evaluated in
      mice at various developmental stages. Renal 11betaHSD2 mRNA and protein
      expression were analyzed by quantitative RT-PCR and immunohistochemistry during
      the perinatal period in both species. RESULTS: We demonstrate that, at variance
      with placental 11betaHSD2 activity, renal 11betaHSD2 activity is weak in newborn
      human and mouse and correlates with low renal mRNA levels and absence of
      detectable 11betaHSD2 protein. CONCLUSIONS: We provide evidence for a weak or
      absent expression of neonatal renal 11betaHSD2 that is conserved among species.
      This temporal and tissue-specific 11betaHSD2 expression could represent a
      physiological window for glucocorticoid action yet may constitute an important
      predictive factor for adverse outcomes of glucocorticoid excess through fetal
      programming.

PMID- 22359646
TI  - S phase entry of neural progenitor cells correlates with increased blood flow in
      the young subventricular zone.
AB  - The postnatal subventricular zone (SVZ) contains proliferating neural progenitor
      cells in close proximity to blood vessels. Insults and drug treatments acutely
      stimulate cell proliferation in the SVZ, which was assessed by labeling cells
      entering S phase. Although G1-to-S progression is metabolically demanding on a
      minute-to-hour time scale, it remains unknown whether increased SVZ cell
      proliferation is accompanied by a local hemodynamic response. This neurovascular
      coupling provides energy substrates to active neuronal assemblies. Transcardial
      dye perfusion revealed the presence of capillaries throughout the SVZ that
      constrict upon applications of the thromboxane A(2) receptor agonist U-46119 in
      acute brain slice preparations. We then monitored in vivo blood flow using laser
      Doppler flowmetry via a microprobe located either in the SVZ or a mature network.
      U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and
      the striatum, which are near the ventricle. A 1-hour ventricular injection of
      epidermal and basic fibroblast growth factor (EGF and bFGF) significantly
      increased the percentage of Sox2 transcription factor-positive cells in S phase
      1.5 hours post-injection. This increase was accompanied by a sustained rise in
      blood flow in the SVZ but not in the striatum. Direct growth factor injections
      into the cortex did not alter local blood flow, ruling out direct effects on
      capillaries. These findings suggest that an acute increase in the number of G1-to
      S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may
      provide energy and nutrient for cell cycle progression.

PMID- 22359647
TI  - Trafficking of high avidity HER-2/neu-specific T cells into HER-2/neu-expressing
      tumors after depletion of effector/memory-like regulatory T cells.
AB  - BACKGROUND: Cancer vaccines are designed to activate and enhance cancer-antigen
      targeted T cells that are suppressed through multiple mechanisms of immune
      tolerance in cancer-bearing hosts. T regulatory cell (Treg) suppression of tumor
      specific T cells is one barrier to effective immunization. A second mechanism is
      the deletion of high avidity tumor-specific T cells, which leaves a less
      effective low avidity tumor specific T cell repertoire available for activation
      by vaccines. Treg depleting agents including low dose cyclophosphamide (Cy) and
      antibodies that deplete CD25-expressing Tregs have been used with limited success
      to enhance the potency of tumor-specific vaccines. In addition, few studies have
      evaluated mechanisms that activate low avidity cancer antigen-specific T cells.
      Therefore, we developed high and low avidity HER-2/neu-specific TCR transgenic
      mouse colonies specific for the same HER-2/neu epitope to define the tolerance
      mechanisms that specifically affect high versus low avidity tumor-specific T
      cells. METHODOLOGY/PRINCIPAL FINDINGS: High and low avidity CD8(+) T cell
      receptor (TCR) transgenic mice specific for the breast cancer antigen HER-2/neu
      (neu) were developed to provide a purified source of naive, tumor-specific T
      cells that can be used to study tolerance mechanisms. Adoptive transfer studies
      into tolerant FVB/N-derived HER-2/neu transgenic (neu-N) mice demonstrated that
      high avidity, but not low avidity, neu-specific T cells are inhibited by Tregs as
      the dominant tolerizing mechanism. High avidity T cells persisted, produced
      IFNgamma, trafficked into tumors, and lysed tumors after adoptive transfer into
      mice treated with a neu-specific vaccine and low dose Cy to deplete Tregs.
      Analysis of Treg subsets revealed a Cy-sensitive CD4(+)Foxp3(+)CD25(low) tumor
      seeking migratory phenotype, characteristic of effector/memory Tregs, and capable
      of high avidity T cell suppression. CONCLUSION/SIGNIFICANCE: Depletion of
      CD25(low) Tregs allows activation of tumor-clearing high avidity T cells. Thus,
      the development of agents that specifically deplete Treg subsets should translate
      into more effective immunotherapies while avoiding autoimmunity.

PMID- 22359648
TI  - Acute exposure of apigenin induces hepatotoxicity in Swiss mice.
AB  - Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in
      different diseases including cancer. Toxicity of Apigenin is however, least
      explored, and reports are scanty in literature. This warrants dose-specific
      evaluation of toxicity in vivo. In the present study, Apigenin was administered
      intraperitoneally to Swiss mice at doses of 25, 50, 100 and 200 mg/kg. Serum
      levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and
      alkaline phosphatase (ALP) were measured along with the examination of liver
      histology, reactive oxygen species (ROS) in blood, lipid peroxidation (LPO),
      glutathione level, superoxide dismutase activity, catalase activity, glutathione
      S-transferase activity and gene expression in liver tissue. Increase in ALT, AST,
      ALP, ROS, ratio of oxidized to reduced glutathione (GSSG/GSH) and LPO, altered
      enzyme activities along with damaged histoarchitecture in the liver of 100 or 200
      mg/kg Apigenin treated animals were found. Microarray analysis revealed the
      differential expression of genes that correspond to different biologically
      relevant pathways including oxidative stress and apoptosis. In conclusion, these
      results suggested the oxidative stress induced liver damage which may be due to
      the regulation of multiple genes by Apigenin at higher doses in Swiss mice.

PMID- 22359649
TI  - Novel information on the epitope of an inverse agonist monoclonal antibody
      provides insight into the structure of the TSH receptor.
AB  - The TSH receptor (TSHR) comprises an extracellular leucine-rich domain (LRD)
      linked by a hinge region to the transmembrane domain (TMD). Insight into the
      orientation of these components to each other is required for understanding how
      ligands activate the receptor. We previously identified residue E251 at the LRD
      hinge junction as contributing to coupling TSH binding with receptor activation.
      However, a single residue cannot stabilize the LRD-hinge unit. Therefore, based
      on the LRD crystal structure we selected for study four other potential LRD-hinge
      interface charged residues. Alanine substitutions of individual residues K244,
      E247, K250 and R255 (as well as previously known E251A) did not affect TSH
      binding or function. However, the cumulative mutation of these residues in
      varying permutations, primarily K250A and R255A when associated with E251A,
      partially uncoupled TSH binding and function. These data suggest that these three
      residues, spatially very close to each other at the LRD base, interact with the
      hinge region. Unexpectedly and most important, monoclonal antibody CS-17, a TSHR
      inverse agonist whose epitope straddles the LRD-hinge, was found to interact with
      residues K244 and E247 at the base of the convex LRD surface. These observations,
      together with the functional data, exclude residues K244 and E247 from the TSHR
      LRD-hinge interface. Further, for CS-17 accessibility to K244 and E247, the
      concave surface of the TSHR LRD must be tilted forwards towards the hinge region
      and plasma membrane. Overall, these data provide insight into the mechanism by
      which ligands either activate the TSHR or suppress its constitutive activity.

PMID- 22359650
TI  - Control of tissue growth and cell transformation by the Salvador/Warts/Hippo
      pathway.
AB  - The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth
      that is frequently subverted in human cancer. The key oncoprotein of the SWH
      pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP
      promotes tissue growth and transformation of cultured cells by interacting with
      transcriptional regulatory proteins via its WW domains, or, in the case of the
      TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a
      putative transactivation domain in its C-terminus that is necessary to stimulate
      transcription factors in vitro, but its requirement for YAP function has not been
      investigated in detail. Interestingly, whilst the WW domains and TEAD-binding
      domain are highly conserved in the Drosophila melanogaster YAP orthologue,
      Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To
      investigate this apparent conundrum, we assessed the functional roles of the YAP
      and Yorkie C-termini. We found that these regions were not required for Yorkie's
      ability to drive tissue growth in vivo, or YAP's ability to promote anchorage
      independent growth or resistance to contact inhibition. However, the YAP
      transactivation domain was required for YAP's ability to induce cell migration
      and invasion. Moreover, a role for the YAP transactivation domain in cell
      transformation was uncovered when the YAP WW domains were mutated together with
      the transactivation domain. This shows that YAP can promote cell transformation
      in a flexible manner, presumably by contacting transcriptional regulatory
      proteins either via its WW domains or its transactivation domain.

PMID- 22359652
TI  - Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone
      and agonist-induced contraction in rat resistance arteries.
AB  - BACKGROUND: Bile acids (BAs) regulate cardiovascular function via diverse
      mechanisms. Although in both health and disease serum glycine-conjugated BAs are
      more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT), a
      key determinant of systemic vascular resistance (SVR), have not been examined.
      METHODOLOGY/PRINCIPAL FINDINGS: Fourth-order mesenteric arteries (170-250 um)
      isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to
      develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 uM),
      a glycine-conjugated major secondary BA, induced reversible, concentration
      dependent reduction of MT that was similar in endothelium-intact and -denuded
      arteries. DCG reduced the myogenic response to stepwise increase in pressure (20
      to 100 mmHg). Neither atropine nor the combination of L-NAME (a NOS inhibitor)
      plus indomethacin altered DCG-mediated reduction of MT. K(+) channel blockade
      with glibenclamide (K(ATP)), 4-aminopyradine (K(V)), BaCl(2) (K(IR)) or
      tetraethylammonium (TEA, K(Ca)) were also ineffective. In Fluo-2-loaded arteries,
      DCG markedly reduced vascular smooth muscle cell (VSM) Ca(2+) fluorescence
      (~50%). In arteries incubated with DCG, physiological salt solution (PSS) with
      high Ca(2+) (4 mM) restored myogenic response. DCG reduced vascular tone and VSM
      cytoplasmic Ca(2+) responses (~50%) of phenylephrine (PE)- and Ang II-treated
      arteries, but did not affect KCl-induced vasoconstriction. CONCLUSION: In rat
      mesenteric resistance arteries DCG reduces pressure- and agonist-induced
      vasoconstriction and VSM cytoplasmic Ca(2+) responses, independent of muscarinic
      receptor, NO or K(+) channel activation. We conclude that BAs alter vasomotor
      responses, an effect favoring reduced SVR. These findings are likely pertinent to
      vascular dysfunction in cirrhosis and other conditions associated with elevated
      serum BAs.

PMID- 22359653
TI  - Dopamine modulates the rest period length without perturbation of its power law
      distribution in Drosophila melanogaster.
AB  - We analyzed the effects of dopamine signaling on the temporal organization of
      rest and activity in Drosophila melanogaster. Locomotor behaviors were recorded
      using a video-monitoring system, and the amounts of movements were quantified by
      using an image processing program. We, first, confirmed that rest bout durations
      followed long-tailed (i.e., power-law) distributions, whereas activity bout
      durations did not with a strict method described by Clauset et al. We also
      studied the effects of circadian rhythm and ambient temperature on rest bouts and
      activity bouts. The fraction of activity significantly increased during
      subjective day and at high temperature, but the power-law exponent of the rest
      bout distribution was not affected. The reduction in rest was realized by
      reduction in long rest bouts. The distribution of activity bouts did not change
      drastically under the above mentioned conditions. We then assessed the effects of
      dopamine. The distribution of rest bouts became less long-tailed and the time
      spent in activity significantly increased after the augmentation of dopamine
      signaling. Administration of a dopamine biosynthesis inhibitor yielded the
      opposite effects. However, the distribution of activity bouts did not contribute
      to the changes. These results suggest that the modulation of locomotor behavior
      by dopamine is predominantly controlled by changing the duration of rest bouts,
      rather than the duration of activity bouts.

PMID- 22359651
TI  - Transcriptional activity and nuclear localization of Cabut, the Drosophila
      ortholog of vertebrate TGF-beta-inducible early-response gene (TIEG) proteins.
AB  - BACKGROUND: Cabut (Cbt) is a C(2)H(2)-class zinc finger transcription factor
      involved in embryonic dorsal closure, epithelial regeneration and other
      developmental processes in Drosophila melanogaster. Cbt orthologs have been
      identified in other Drosophila species and insects as well as in vertebrates.
      Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins
      encoded by the TGF-beta-inducible early-response genes (TIEGs), which belong to
      Sp1-like/Kruppel-like family of transcription factors. Several functional domains
      involved in transcriptional control and subcellular localization have been
      identified in the vertebrate TIEGs. However, little is known of whether these
      domains and functions are also conserved in the Cbt protein.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine the transcriptional regulatory
      activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays
      in S2 cells and showed that Cbt is a transcriptional repressor and able to
      regulate its own expression. Truncated forms of Cbt were then generated to
      identify its functional domains. This analysis revealed a sequence similar to the
      mSin3A-interacting repressor domain found in vertebrate TIEGs, although located
      in a different part of the Cbt protein. Using beta-Galactosidase and eGFP fusion
      proteins, we also showed that Cbt contains the bipartite nuclear localization
      signal (NLS) previously identified in TIEG proteins, although it is non
      functional in insect cells. Instead, a monopartite NLS, located at the amino
      terminus of the protein and conserved across insects, is functional in Drosophila
      S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction
      and immunohistochemical assays suggested that Cbt nuclear import is mediated by
      Importin-alpha2. CONCLUSIONS/SIGNIFICANCE: Our results constitute the first
      characterization of the molecular mechanisms of Cbt-mediated transcriptional
      control as well as of Cbt nuclear import, and demonstrate the existence of
      similarities and differences in both aspects of Cbt function between the insect
      and the vertebrate TIEG proteins.

PMID- 22359654
TI  - A highly conserved, small LTR retrotransposon that preferentially targets genes
      in grass genomes.
AB  - LTR retrotransposons are often the most abundant components of plant genomes and
      can impact gene and genome evolution. Most reported LTR retrotransposons are
      large elements (>4 kb) and are most often found in heterochromatic (gene poor)
      regions. We report the smallest LTR retrotransposon found to date, only 292 bp.
      The element is found in rice, maize, sorghum and other grass genomes, which
      indicates that it was present in the ancestor of grass species, at least 50-80
      MYA. Estimated insertion times, comparisons between sequenced rice lines, and
      mRNA data indicate that this element may still be active in some genomes. Unlike
      other LTR retrotransposons, the small LTR retrotransposons (SMARTs) are
      distributed throughout the genomes and are often located within or near genes
      with insertion patterns similar to MITEs (miniature inverted repeat transposable
      elements). Our data suggests that insertions of SMARTs into or near genes can, in
      a few instances, alter both gene structures and gene expression. Further evidence
      for a role in regulating gene expression, SMART-specific small RNAs (sRNAs) were
      identified that may be involved in gene regulation. Thus, SMARTs may have played
      an important role in genome evolution and genic innovation and may provide a
      valuable tool for gene tagging systems in grass.

PMID- 22359655
TI  - A measure of the promiscuity of proteins and characteristics of residues in the
      vicinity of the catalytic site that regulate promiscuity.
AB  - Promiscuity, the basis for the evolution of new functions through 'tinkering' of
      residues in the vicinity of the catalytic site, is yet to be quantitatively
      defined. We present a computational method Promiscuity Indices Estimator
      (PROMISE)--based on signatures derived from the spatial and electrostatic
      properties of the catalytic residues, to estimate the promiscuity (PromIndex) of
      proteins with known active site residues and 3D structure. PromIndex reflects the
      number of different active site signatures that have congruent matches in close
      proximity of its native catalytic site, the quality of the matches and difference
      in the enzymatic activity. Promiscuity in proteins is observed to follow a
      lognormal distribution (MU = 0.28, sigma = 1.1 reduced chi-square = 3.0E-5). The
      PROMISE predicted promiscuous functions in any protein can serve as the starting
      point for directed evolution experiments. PROMISE ranks carboxypeptidase A and
      ribonuclease A amongst the more promiscuous proteins. We have also investigated
      the properties of the residues in the vicinity of the catalytic site that
      regulates its promiscuity. Linear regression establishes a weak correlation
      (R(2)~0.1) between certain properties of the residues (charge, polar, etc) in the
      neighborhood of the catalytic residues and PromIndex. A stronger relationship
      states that most proteins with high promiscuity have high percentages of charged
      and polar residues within a radius of 3 A of the catalytic site, which is
      validated using one-tailed hypothesis tests (P-values~0.05). Since it is known
      that these characteristics are key factors in catalysis, their relationship with
      the promiscuity index cross validates the methodology of PROMISE.

PMID- 22359656
TI  - A novel cold-regulated cold shock domain containing protein from scallop Chlamys
      farreri with nucleic acid-binding activity.
AB  - BACKGROUND: The cold shock domain (CSD) containing proteins (CSDPs) are one group
      of the evolutionarily conserved nucleic acid-binding proteins widely distributed
      in bacteria, plants, animals, and involved in various cellular processes,
      including adaptation to low temperature, cellular growth, nutrient stress and
      stationary phase. METHODOLOGY: The cDNA of a novel CSDP was cloned from Zhikong
      scallop Chlamys farreri (designated as CfCSP) by expressed sequence tag (EST)
      analysis and rapid amplification of cDNA ends (RACE) approach. The full length
      cDNA of CfCSP was of 1735 bp containing a 927 bp open reading frame which encoded
      an N-terminal CSD with conserved nucleic acids binding motif and a C-terminal
      domain with four Arg-Gly-Gly (RGG) repeats. The CSD of CfCSP shared high homology
      with the CSDs from other CSDPs in vertebrate, invertebrate and bacteria. The mRNA
      transcripts of CfCSP were mainly detected in the tissue of adductor and also
      marginally detectable in gill, hepatopancreas, hemocytes, kidney, mantle and
      gonad of healthy scallop. The relative expression level of CfCSP was up-regulated
      significantly in adductor and hemocytes at 1 h and 24 h respectively after low
      temperature treatment (P<0.05). The recombinant CfCSP protein (rCfCSP) could bind
      ssDNA and in vitro transcribed mRNA, but it could not bind dsDNA. BX04, a cold
      sensitive Escherichia coli CSP quadruple-deletion mutant, was used to examine the
      cold adaptation ability of CfCSP. After incubation at 17 degrees C for 120 h, the
      strain of BX04 containing the vector pINIII showed growth defect and failed to
      form colonies, while strain containing pINIII-CSPA or pINIII-CfCSP grew
      vigorously, indicating that CfCSP shared a similar function with E. coli CSPs for
      the cold adaptation. CONCLUSIONS: These results suggest that CfCSP is a novel
      eukaryotic cold-regulated nucleic acid-binding protein and may function as an RNA
      chaperone in vivo during the cold adaptation process.

PMID- 22359657
TI  - The two different isoforms of the RSC chromatin remodeling complex play distinct
      roles in DNA damage responses.
AB  - The RSC chromatin remodeling complex has been implicated in contributing to DNA
      double-strand break (DSB) repair in a number of studies. Both survival and levels
      of H2A phosphorylation in response to damage are reduced in the absence of RSC.
      Importantly, there is evidence for two isoforms of this complex, defined by the
      presence of either Rsc1 or Rsc2. Here, we investigated whether the two isoforms
      of RSC provide distinct contributions to DNA damage responses. First, we
      established that the two isoforms of RSC differ in the presence of Rsc1 or Rsc2
      but otherwise have the same subunit composition. We found that both rsc1 and rsc2
      mutant strains have intact DNA damage-induced checkpoint activity and
      transcriptional induction. In addition, both strains show reduced non-homologous
      end joining activity and have a similar spectrum of DSB repair junctions,
      suggesting perhaps that the two complexes provide the same functions. However,
      the hypersensitivity of a rsc1 strain cannot be complemented with an extra copy
      of RSC2, and likewise, the hypersensitivity of the rsc2 strain remains unchanged
      when an additional copy of RSC1 is present, indicating that the two proteins are
      unable to functionally compensate for one another in DNA damage responses. Rsc1,
      but not Rsc2, is required for nucleosome sliding flanking a DNA DSB.
      Interestingly, while swapping the domains from Rsc1 into the Rsc2 protein does
      not compromise hypersensitivity to DNA damage suggesting they are functionally
      interchangeable, the BAH domain from Rsc1 confers upon Rsc2 the ability to
      remodel chromatin at a DNA break. These data demonstrate that, despite the
      similarity between Rsc1 and Rsc2, the two different isoforms of RSC provide
      distinct functions in DNA damage responses, and that at least part of the
      functional specificity is dictated by the BAH domains.

PMID- 22359658
TI  - Recognition of anesthetic barbiturates by a protein binding site: a high
      resolution structural analysis.
AB  - Barbiturates potentiate GABA actions at the GABA(A) receptor and act as central
      nervous system depressants that can induce effects ranging from sedation to
      general anesthesia. No structural information has been available about how
      barbiturates are recognized by their protein targets. For this reason, we tested
      whether these drugs were able to bind specifically to horse spleen apoferritin, a
      model protein that has previously been shown to bind many anesthetic agents with
      affinities that are closely correlated with anesthetic potency. Thiopental,
      pentobarbital, and phenobarbital were all found to bind to apoferritin with
      affinities ranging from 10-500 uM, approximately matching the concentrations
      required to produce anesthetic and GABAergic responses. X-ray crystal structures
      were determined for the complexes of apoferritin with thiopental and
      pentobarbital at resolutions of 1.9 and 2.0 A, respectively. These structures
      reveal that the barbiturates bind to a cavity in the apoferritin shell that also
      binds haloalkanes, halogenated ethers, and propofol. Unlike these other general
      anesthetics, however, which rely entirely upon van der Waals interactions and the
      hydrophobic effect for recognition, the barbiturates are recognized in the
      apoferritin site using a mixture of both polar and nonpolar interactions. These
      results suggest that any protein binding site that is able to recognize and
      respond to the chemically and structurally diverse set of compounds used as
      general anesthetics is likely to include a versatile mixture of both polar and
      hydrophobic elements.

PMID- 22359659
TI  - Changes in temperature have opposing effects on current amplitude in alpha7 and
      alpha4beta2 nicotinic acetylcholine receptors.
AB  - We have examined the effect of temperature on the electrophysiological properties
      of three neuronal nicotinic acetylcholine receptor (NACHR) subtypes: the rapidly
      desensitizing homomeric alpha7 nAChR, the more slowly desensitizing heteromeric
      alpha4beta2 nAChR and on alpha7 nAChRs containing a transmembrane mutation
      (L247T) that results in dramatically reduced desensitization. In all cases, the
      functional properties of receptors expressed in Xenopus oocytes at room
      temperature (RT; 21 degrees C) were compared to those recorded at either
      physiological temperature (37 degrees C) or at lower temperature (4 degrees C).
      Alterations in temperature had dramatically differing effects on the amplitude of
      whole-cell responses detected with these three nAChR subtypes. Compared to
      responses at RT, the amplitude of agonist-evoked responses with alpha4beta2
      nAChRs was increased at high temperature (125+/-9%, n = 6, P<0.01) and reduced at
      low temperature (47+/-5%, n = 6, P<0.01), whereas the amplitude of alpha7
      responses was reduced at high temperature (27+/-7%, n = 11, P<0.001) and
      increased at low temperatures (224+/-16%, n = 10, P<0.001). In contrast to the
      effects of temperature on alpha4beta2 and wild type alpha7 nAChRs, the amplitude
      of alpha7 nAChRs containing the L247T mutation was unaffected by changes in
      temperature. In addition, changes in temperature had little or no effect on
      current amplitude when alpha7 nAChRs were activated by the largely non
      desensitizing allosteric agonist 4BP-TQS. Despite these differing effects of
      temperature on the amplitude of agonist-evoked responses in different nAChRs,
      changes in temperature had a consistent effect on the rate of receptor
      desensitization on all subtypes examined. In all cases, higher temperature
      resulted in increased rates of desensitization. Thus, it appears that the
      differing effects of temperature on the amplitudes of whole-cell responses cannot
      be explained by temperature-induced changes in receptor desensitization rates.

PMID- 22359660
TI  - The effects of warming-shifted plant phenology on ecosystem carbon exchange are
      regulated by precipitation in a semi-arid grassland.
AB  - BACKGROUND: The longer growing season under climate warming has served as a
      crucial mechanism for the enhancement of terrestrial carbon (C) sink over the
      past decades. A better understanding of this mechanism is critical for projection
      of changes in C cycling of terrestrial ecosystems. METHODOLOGY/PRINCIPAL
      FINDINGS: A 4-year field experiment with day and night warming was conducted to
      examine the responses of plant phenology and their influences on plant coverage
      and ecosystem C cycling in a temperate steppe in northern China. Greater
      phenological responses were observed under night than day warming. Both day and
      night warming prolonged the growing season by advancing phenology of early
      blooming species but without changing that of late-blooming species. However, no
      warming response of vegetation coverage was found for any of the eight species.
      The variances in species-level coverage and ecosystem C fluxes under different
      treatments were positively dependent upon the accumulated precipitation within
      phenological duration but not the length of phenological duration.
      CONCLUSIONS/SIGNIFICANCE: These plants' phenology is more sensitive to night than
      day warming, and the warming effects on ecosystem C exchange via shifting plant
      phenology could be mediated by precipitation patterns in semi-arid grasslands.

PMID- 22359661
TI  - A stochastic step model of replicative senescence explains ROS production rate in
      ageing cell populations.
AB  - Increases in cellular Reactive Oxygen Species (ROS) concentration with age have
      been observed repeatedly in mammalian tissues. Concomitant increases in the
      proportion of replicatively senescent cells in ageing mammalian tissues have also
      been observed. Populations of mitotic human fibroblasts cultured in vitro,
      undergoing transition from proliferation competence to replicative senescence are
      useful models of ageing human tissues. Similar exponential increases in ROS with
      age have been observed in this model system. Tracking individual cells in
      dividing populations is difficult, and so the vast majority of observations have
      been cross-sectional, at the population level, rather than longitudinal
      observations of individual cells.One possible explanation for these observations
      is an exponential increase in ROS in individual fibroblasts with time (e.g.
      resulting from a vicious cycle between cellular ROS and damage). However, we
      demonstrate an alternative, simple hypothesis, equally consistent with these
      observations which does not depend on any gradual increase in ROS concentration:
      the Stochastic Step Model of Replicative Senescence (SSMRS). We also demonstrate
      that, consistent with the SSMRS, neither proliferation-competent human
      fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts
      passaged beyond the Hayflick limit, display high ROS concentrations. We conclude
      that longitudinal studies of single cells and their lineages are now required for
      testing hypotheses about roles and mechanisms of ROS increase during replicative
      senescence.

PMID- 22359662
TI  - IL-17 mediated inflammation promotes tumor growth and progression in the skin.
AB  - The mechanism for inflammation associated tumor development is a central issue
      for tumor biology and immunology and remains to be fully elucidated. Although IL
      17 is implicated in association with inflammation mediated carcinogenesis,
      mechanisms are largely elusive. In the current studies, we showed that IL-17
      receptor-A gene deficient (IL-17R-/-) mice were resistant to chemical carcinogen
      induced cutaneous carcinogenesis, a well-established inflammation associated
      tumor model in the skin. The deficiency in IL-17R increased the infiltration of
      CD8+ T cells whereas it inhibited the infiltration of CD11b+ myeloid cells and
      development of myeloid derived suppressor cells. Inflammation induced skin
      hyperplasia and production of pro-tumor inflammatory molecules were inhibited in
      IL-17R-/- mice. We found that pre-existing inflammation in the skin increased the
      susceptibility to tumor growth, which was associated with increased development
      of tumor specific IL-17 producing T cells. This inflammation induced
      susceptibility to tumor growth was abrogated in IL-17R-/- mice. Finally,
      neutralizing IL-17 in mice that had already developed chemical carcinogen induced
      skin tumors could inhibit inflammation mediated tumor progression at late stages.
      These results demonstrate that IL-17 mediated inflammation is an important
      mechanism for inflammation mediated promotion of tumor development. The study has
      major implications for targeting IL-17 in prevention and treatment of tumors.

PMID- 22359663
TI  - ARF1 and GBF1 generate a PI4P-enriched environment supportive of hepatitis C
      virus replication.
AB  - Cellular levels of phosphatidylinositol 4-phosphate (PI4P) have been shown to be
      upregulated during RNA replication of several viruses, including the HCV replicon
      model. However, whether PI4P is required in an infectious HCV model remains
      unknown. Moreover, it is not established whether the host transport machinery is
      sequestered by the generation of PI4P during HCV infection. Here we found that
      PI4P was enriched in HCV replication complexes when Huh7.5.1 cells were infected
      with JFH1. HCV replication was inhibited upon overexpression of the PI4P
      phosphatase Sac1. The PI4P kinase PI4KIIIbeta was also found to be required for
      HCV replication. Moreover, the vesicular transport proteins ARF1 and GBF1
      colocalized with PI4KIIIbeta and were both required for HCV replication. During
      authentic HCV infection, PI4P plays an integral role in virus replication.

PMID- 22359664
TI  - A novel protein kinase-like domain in a selenoprotein, widespread in the tree of
      life.
AB  - Selenoproteins serve important functions in many organisms, usually providing
      essential oxidoreductase enzymatic activity, often for defense against toxic
      xenobiotic substances. Most eukaryotic genomes possess a small number of these
      proteins, usually not more than 20. Selenoproteins belong to various structural
      classes, often related to oxidoreductase function, yet a few of them are
      completely uncharacterised.Here, the structural and functional prediction for the
      uncharacterised selenoprotein O (SELO) is presented. Using bioinformatics tools,
      we predict that SELO protein adopts a three-dimensional fold similar to protein
      kinases. Furthermore, we argue that despite the lack of conservation of the
      "classic" catalytic aspartate residue of the archetypical His-Arg-Asp motif, SELO
      kinases might have retained catalytic phosphotransferase activity, albeit with an
      atypical active site. Lastly, the role of the selenocysteine residue is
      considered and the possibility of an oxidoreductase-regulated kinase function for
      SELO is discussed.The novel kinase prediction is discussed in the context of
      functional data on SELO orthologues in model organisms, FMP40 a.k.a.YPL222W
      (yeast), and ydiU (bacteria). Expression data from bacteria and yeast suggest a
      role in oxidative stress response. Analysis of genomic neighbourhoods of SELO
      homologues in the three domains of life points toward a role in regulation of ABC
      transport, in oxidative stress response, or in basic metabolism regulation. Among
      bacteria possessing SELO homologues, there is a significant over-representation
      of aquatic organisms, also of aerobic ones. The selenocysteine residue in SELO
      proteins occurs only in few members of this protein family, including proteins
      from Metazoa, and few small eukaryotes (Ostreococcus, stramenopiles). It is also
      demonstrated that enterobacterial mchC proteins involved in maturation of
      bactericidal antibiotics, microcins, form a distant subfamily of the SELO
      proteins.The new protein structural domain, with a putative kinase function
      assigned, expands the known kinome and deserves experimental determination of its
      biological role within the cell-signaling network.

PMID- 22359665
TI  - Comorbidity patterns in patients with chronic diseases in general practice.
AB  - INTRODUCTION: Healthcare management is oriented toward single diseases, yet
      multimorbidity is nevertheless the rule and there is a tendency for certain
      diseases to occur in clusters. This study sought to identify comorbidity patterns
      in patients with chronic diseases, by reference to number of comorbidities, age
      and sex, in a population receiving medical care from 129 general practitioners in
      Spain, in 2007. METHODS: A cross-sectional study was conducted in a health-area
      setting of the Madrid Autonomous Region (Comunidad Autonoma), covering a
      population of 198,670 individuals aged over 14 years. Multiple correspondences
      were analyzed to identify the clustering patterns of the conditions targeted.
      RESULTS: Forty-two percent (95% confidence interval [CI]: 41.8-42.2) of the
      registered population had at least one chronic condition. In all, 24.5% (95% CI:
      24.3-24.6) of the population presented with multimorbidity. In the correspondence
      analysis, 98.3% of the total information was accounted for by three dimensions.
      The following four, age- and sex-related comorbidity patterns were identified:
      pattern B, showing a high comorbidity rate; pattern C, showing a low comorbidity
      rate; and two patterns, A and D, showing intermediate comorbidity rates.
      CONCLUSIONS: Four comorbidity patterns could be identified which grouped diseases
      as follows: one showing diseases with a high comorbidity burden; one showing
      diseases with a low comorbidity burden; and two showing diseases with an
      intermediate comorbidity burden.

PMID- 22359666
TI  - Altered bone development and an increase in FGF-23 expression in Enpp1(-/-) mice.
AB  - Nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) is required for the
      conversion of extracellular ATP into inorganic pyrophosphate (PP(i)), a
      recognised inhibitor of hydroxyapatite (HA) crystal formation. A detailed
      phenotypic assessment of a mouse model lacking NPP1 (Enpp1(-/-)) was completed to
      determine the role of NPP1 in skeletal and soft tissue mineralization in juvenile
      and adult mice. Histopathological assessment of Enpp1(-/-) mice at 22 weeks of
      age revealed calcification in the aorta and kidney and ectopic cartilage
      formation in the joints and spine. Radiographic assessment of the hind-limb
      showed hyper-mineralization in the talocrural joint and hypo-mineralization in
      the femur and tibia. MicroCT analysis of the tibia and femur disclosed altered
      trabecular architecture and bone geometry at 6 and 22 weeks of age in Enpp1(-/-)
      mice. Trabecular number, trabecular bone volume, structure model index,
      trabecular and cortical thickness were all significantly reduced in tibiae and
      femurs from Enpp1(-/-) mice (P<0.05). Bone stiffness as determined by 3-point
      bending was significantly reduced in Enpp1(-/-) tibiae and femurs from 22-week
      old mice (P<0.05). Circulating phosphate and calcium levels were reduced (P<0.05)
      in the Enpp1(-/-) null mice. Plasma levels of osteocalcin were significantly
      decreased at 6 weeks of age (P<0.05) in Enpp1(-/-) mice, with no differences
      noted at 22 weeks of age. Plasma levels of CTx (RatlapsTM) and the phosphaturic
      hormone FGF-23 were significantly increased in the Enpp1(-/-) mice at 22 weeks of
      age (P<0.05). Fgf-23 messenger RNA expression in cavarial osteoblasts was
      increased 12-fold in Enpp1(-/-) mice compared to controls. These results indicate
      that Enpp1(-/-) mice are characterized by severe disruption to the architecture
      and mineralization of long-bones, dysregulation of calcium/phosphate homeostasis
      and changes in Fgf-23 expression. We conclude that NPP1 is essential for normal
      bone development and control of physiological bone mineralization.

PMID- 22359667
TI  - C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.
AB  - The planar cell polarity (PCP) pathway is highly conserved from Drosophila to
      humans and a PCP-like pathway has recently been described in the nematode
      Caenorhabditis elegans. The developmental function of this pathway is to
      coordinate the orientation of cells or structures within the plane of an
      epithelium or to organize cell-cell intercalation required for correct
      morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans
      ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two
      alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean
      life span up to 40%. Consistent with the longevity phenotype vang-1 animals also
      show enhanced resistance to thermal- and oxidative stress and decreased
      lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced
      brood size, decreased ovulation rate and prolonged reproductive span, which are
      also related to gerontogenes. The germline, but not the intestine or neurons,
      seems to be the primary site of vang-1 function. Life span extension in vang-1
      mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO
      transcription factor. RNAi against the phase II detoxification transcription
      factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by
      gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first
      time that a key player of the PCP pathway is shown to be involved in the
      insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

PMID- 22359668
TI  - Targeting lysophosphatidic acid signaling retards culture-associated senescence
      of human marrow stromal cells.
AB  - Marrow stromal cells (MSCs) isolated from mesenchymal tissues can propagate in
      vitro to some extent and differentiate into various tissue lineages to be used
      for cell-based therapies. Cellular senescence, which occurs readily in continual
      MSC culture, leads to loss of these characteristic properties, representing one
      of the major limitations to achieving the potential of MSCs. In this study, we
      investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite
      in membrane phospholipid synthesis, on the senescence program of human MSCs. We
      show that MSCs preferentially express the LPA receptor subtype 1, and an
      abrogation of the receptor engagement with the antagonistic compound Ki16425
      attenuates senescence induction in continually propagated human MSCs. This anti
      aging effect of Ki16425 results in extended rounds of cellular proliferation,
      increased clonogenic potential, and retained plasticity for osteogenic and
      adipogenic differentiation. Expressions of p16(Ink4a), Rb, p53, and p21(Cip1),
      which have been associated with cellular senescence, were all reduced in human
      MSCs by the pharmacological inhibition of LPA signaling. Disruption of this
      signaling pathway was accompanied by morphological changes such as cell thinning
      and elongation as well as actin filament deformation through decreased
      phosphorylation of focal adhesion kinase. Prevention of LPA receptor engagement
      also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently
      the entry into a quiescent state, G(0) phase, of the cell cycle. Collectively,
      these results highlight the potential of pharmacological intervention against LPA
      signaling for blunting senescence-associated loss of function characteristic of
      human MSCs.

PMID- 22359669
TI  - Activation of a helper and not regulatory human CD4+ T cell response by oncolytic
      H-1 parvovirus.
AB  - BACKGROUND: H-1 parvovirus (H-1 PV), a rodent autonomous oncolytic parvovirus,
      has emerged as a novel class of promising anticancer agents, because of its
      ability to selectively find and destroy malignant cells. However, to probe H-1 PV
      multimodal antitumor potential one of the major prerequisites is to decipher H-1
      PV direct interplay with human immune system, and so prevent any risk of
      impairment. METHODOLOGY/PRINCIPAL FINDINGS: Non activated peripheral blood
      mononuclear cells (PBMCs) are not sensitive to H-1 PV cytotoxic effect. However,
      the virus impairs both activated PBMC proliferation ability and viability. This
      effect is related to H-1 PV infection as evidenced by Western blotting detection
      of H-1 PV main protein NS1. However, TCID50 experiments did not allow newly
      generated virions to be detected. Moreover, flow cytometry has shown that H-1 PV
      preferentially targets B lymphocytes. Despite seeming harmful at first sight, H-1
      PV seems to affect very few NK cells and CD8+ T lymphocytes and, above all,
      clearly does not affect human neutrophils and one of the major CD4+ T lymphocyte
      subpopulation. Very interestingly, flow cytometry analysis and ELISA assays
      proved that it even activates human CD4+ T cells by increasing activation marker
      expression (CD69 and CD30) and both effective Th1 and Th2 cytokine secretion (IL
      2, IFN-gamma and IL-4). In addition, H-1 PV action does not come with any sign of
      immunosuppressive side effect. Finally, we have shown the efficiency of H-1 PV on
      xenotransplanted human nasopharyngeal carcinoma, in a SCID mouse model
      reconstituted with human PBMC. CONCLUSIONS/SIGNIFICANCE: Our results show for the
      first time that a wild-type oncolytic virus impairs some immune cell
      subpopulations while directly activating a Helper CD4+ T cell response. Thus, our
      data open numerous gripping perspectives of investigation and strongly argue for
      the use of H-1 PV as an anticancer treatment.

PMID- 22359670
TI  - Predicting the current and future potential distributions of lymphatic filariasis
      in Africa using maximum entropy ecological niche modelling.
AB  - Modelling the spatial distributions of human parasite species is crucial to
      understanding the environmental determinants of infection as well as for guiding
      the planning of control programmes. Here, we use ecological niche modelling to
      map the current potential distribution of the macroparasitic disease, lymphatic
      filariasis (LF), in Africa, and to estimate how future changes in climate and
      population could affect its spread and burden across the continent. We used 508
      community-specific infection presence data collated from the published literature
      in conjunction with five predictive environmental/climatic and demographic
      variables, and a maximum entropy niche modelling method to construct the first
      ecological niche maps describing potential distribution and burden of LF in
      Africa. We also ran the best-fit model against climate projections made by the
      HADCM3 and CCCMA models for 2050 under A2a and B2a scenarios to simulate the
      likely distribution of LF under future climate and population changes. We predict
      a broad geographic distribution of LF in Africa extending from the west to the
      east across the middle region of the continent, with high probabilities of
      occurrence in the Western Africa compared to large areas of medium probability
      interspersed with smaller areas of high probability in Central and Eastern Africa
      and in Madagascar. We uncovered complex relationships between predictor
      ecological niche variables and the probability of LF occurrence. We show for the
      first time that predicted climate change and population growth will expand both
      the range and risk of LF infection (and ultimately disease) in an endemic region.
      We estimate that populations at risk to LF may range from 543 and 804 million
      currently, and that this could rise to between 1.65 to 1.86 billion in the future
      depending on the climate scenario used and thresholds applied to signify
      infection presence.

PMID- 22359671
TI  - Lack of functional selectin ligand interactions compromises long term tumor
      protection by CD8+ T cells.
AB  - Central memory CD8(+) T cells expressing the adhesion molecule CD62L (L-selectin)
      are potent mediators of anti-cancer immunity due to their ability to proliferate
      extensively upon antigen re-stimulation. The interaction of selectin with its
      ligands mediates leukocyte rolling along high endothelial venules. Mice deficient
      in alpha(1,3) Fucosyltransferase IV and VII (FtDKO) lack functional L, P and E
      selectin ligands. Thus, we addressed whether the lack of selectin ligand
      interactions alters tumor protection by CD8(+) T cells in FtDKO mice. Listeria
      monocytogenes-OVA (LM-OVA) infection evoked potent OVA-specific CD8(+) T cells
      that proliferated and contracted at similar kinetics and phenotype in FtDKO and
      wild-type mice. Additionally, OVA-specific CD8(+) T cells in both mouse strains
      exhibited similar phenotypic differentiation, in vivo cytolytic activity and IFN
      gamma expression. However, FtDKO mice succumbed to B16-OVA tumors significantly
      earlier than wild-type mice. In contrast, FtDKO mice evoked strong recall memory
      CD8(+) T cell responses and protection to systemic LM-OVA re-challenge. The
      diminished tumor protection in FtDKO mice was not related to defective antigen
      presentation by dendritic cells or reduced proliferation of antigen-specific
      CD8(+) T cells. However, WT or FtDKO OVA-specific CD8(+) T cells showed
      significantly reduced ability to traffic to lymph nodes upon adoptive transfer
      into naive FtDKO recipients. Furthermore, FtDKO OVA-specific CD8(+) T cells
      displayed poor ability to infiltrate tumors growing in WT mice. These results
      reveal that selectin ligand expression on host endothelium as well CD8(+) T cells
      may be important for their efficient and continued extravasation into peripheral
      tumors.

PMID- 22359672
TI  - Elevated cerebral spinal fluid cytokine levels in boys with cerebral
      adrenoleukodystrophy correlates with MRI severity.
AB  - BACKGROUND: X-linked adrenoleukodystrophy (ALD) is a metabolic, peroxisomal
      disease that results from a mutation in the ABCD1 gene. The most severe course of
      ALD progression is the cerebral inflammatory and demyelinating form of the
      disease, cALD. To date there is very little information on the cytokine mediators
      in the cerebral spinal fluid (CSF) of these boys. METHODOLOGY/PRINCIPAL FINDINGS:
      Measurement of 23 different cytokines was performed on CSF and serum of boys with
      cerebral ALD and patients without ALD. Significant elevations in CSF IL-8 (29.3+/
      2.2 vs 12.8+/-1.1 pg/ml, p = 0.0001), IL-1ra (166+/-30 vs 8.6+/-6.5 pg/ml, p =
      0.005), MCP-1 (610+/-47 vs 328+/-34 pg/ml, p = 0.002), and MIP-1b (14.2+/-1.3 vs
      2.0+/-1.4 pg/ml, p<0.0001) were found in boys with cALD versus the control group.
      The only serum cytokine showing an elevation in the ALD group was SDF-1 (2124+/
      155 vs 1175+/-125 pg/ml, p = 0.0001). The CSF cytokines of IL-8 and MCP-1b
      correlated with the Loes MRI severity score (p = 0.04 and p = 0.008
      respectively), as well as the serum SDF-1 level (p = 0.002). Finally, CSF total
      protein was also significantly elevated in boys with cALD and correlated with
      both IL-8, MCP-1b (p = 0.0001 for both), as well as Loes MRI severity score (p =
      0.0007). CONCLUSIONS/SIGNIFICANCE: IL-8, IL-1ra, MCP-1, MIP-1b and CSF total
      protein were significantly elevated in patients with cALD; IL-8, MCP-1b, and CSF
      total protein levels correlated with disease severity determined by MRI. This is
      the largest report of CSF cytokine levels in cALD to date, and identification of
      these key cytokines will provide further insight into disease progression and
      perhaps lead to improved targeted therapies.

PMID- 22359673
TI  - Predatory functional response and prey choice identify predation differences
      between native/invasive and parasitised/unparasitised crayfish.
AB  - BACKGROUND: Invasive predators may change the structure of invaded communities
      through predation and competition with native species. In Europe, the invasive
      signal crayfish Pacifastacus leniusculus is excluding the native white clawed
      crayfish Austropotamobius pallipes. METHODOLOGY AND PRINCIPAL FINDINGS: This
      study compared the predatory functional responses and prey choice of native and
      invasive crayfish and measured impacts of parasitism on the predatory strength of
      the native species. Invasive crayfish showed a higher (>10%) prey (Gammarus
      pulex) intake rate than (size matched) natives, reflecting a shorter (16%) prey
      handling time. The native crayfish also showed greater selection for crustacean
      prey over molluscs and bloodworm, whereas the invasive species was a more
      generalist predator. A. pallipes parasitised by the microsporidian parasite
      Thelohania contejeani showed a 30% reduction in prey intake. We suggest that this
      results from parasite-induced muscle damage, and this is supported by a reduced
      (38%) attack rate and increased (30%) prey handling time. CONCLUSIONS AND
      SIGNIFICANCE: Our results indicate that the per capita (i.e., functional
      response) difference between the species may contribute to success of the invader
      and extinction of the native species, as well as decreased biodiversity and
      biomass in invaded rivers. In addition, the reduced predatory strength of
      parasitized natives may impair their competitive abilities, facilitating
      exclusion by the invader.

PMID- 22359674
TI  - A biphasic and brain-region selective down-regulation of cyclic adenosine
      monophosphate concentrations supports object recognition in the rat.
AB  - BACKGROUND: We aimed to further understand the relationship between cAMP
      concentration and mnesic performance. METHODS AND FINDINGS: Rats were injected
      with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p.), rolipram (PDE4 inhibitor, 0.3
      mg/kg, i.p.) and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p.) before
      testing in the object recognition paradigm. Cyclic AMP concentrations were
      measured in brain structures linked to episodic-like memory (i.e. hippocampus,
      prefrontal and perirhinal cortices) before or after either the sample or the
      testing phase. Except in the hippocampus of rolipram treated-rats, all treatment
      increased cAMP levels in each brain sub-region studied before the sample phase.
      After the sample phase, cAMP levels were significantly increased in hippocampus
      (1.8 fold), prefrontal (1.3 fold) and perirhinal (1.3 fold) cortices from
      controls rat while decreased in prefrontal cortex (~0.83 to 0.62 fold) from drug
      treated rats (except for milrinone+RS 67333 treatment). After the testing phase,
      cAMP concentrations were still increased in both the hippocampus (2.76 fold) and
      the perirhinal cortex (2.1 fold) from controls animals. Minor increase were
      reported in hippocampus and perirhinal cortex from both rolipram (respectively,
      1.44 fold and 1.70 fold) and milrinone (respectively 1.46 fold and 1.56 fold)
      treated rat. Following the paradigm, cAMP levels were significantly lower in the
      hippocampus, prefrontal and perirhinal cortices from drug-treated rat when
      compared to controls animals, however, only drug-treated rats spent longer time
      exploring the novel object during the testing phase (inter-phase interval of 4
      h). CONCLUSIONS: Our results strongly suggest that a "pre-sample" early increase
      in cAMP levels followed by a specific lowering of cAMP concentrations in each
      brain sub-region linked to the object recognition paradigm support learning
      efficacy after a middle-term delay.

PMID- 22359675
TI  - Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate
      induced apoptotic cell death.
AB  - Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables,
      decreases viability of cancer cells by causing apoptosis but the mechanism of
      cell death is not fully understood. The present study was undertaken to determine
      the role of Bcl-2 family proteins in BITC-induced apoptosis using MDA-MB-231
      (breast), MCF-7 (breast), and HCT-116 (colon) human cancer cells. The B-cell
      lymphoma 2 interacting mediator of cell death (Bim) protein was dispensable for
      proapoptotic response to BITC in MCF-7 and MDA-MB-231 cells as judged by RNA
      interference studies. Instead, the BITC-treated MCF-7 and MDA-MB-231 cells
      exhibited upregulation of p53 upregulated modulator of apoptosis (PUMA) protein.
      The BITC-mediated induction of PUMA was relatively more pronounced in MCF-7 cells
      due to the presence of wild-type p53 compared with MDA-MB-231 with mutant p53.
      The BITC-induced apoptosis was partially but significantly attenuated by RNA
      interference of PUMA in MCF-7 cells. The PUMA knockout variant of HCT-116 cells
      exhibited significant resistance towards BITC-induced apoptosis compared with
      wild-type HCT-116 cells. Attenuation of BITC-induced apoptosis in PUMA knockout
      HCT-116 cells was accompanied by enhanced G2/M phase cell cycle arrest due to
      induction of p21 and down regulation of cyclin-dependent kinase 1 protein. The
      BITC treatment caused a decrease in protein levels of Bcl-xL (MCF-7 and MDA-MB
      231 cells) and Bcl-2 (MCF-7 cells). Ectopic expression of Bcl-xL in MCF-7 and MDA
      MB-231 cells and that of Bcl-2 in MCF-7 cells conferred protection against
      proapoptotic response to BITC. Interestingly, the BITC-treated MDA-MB-231 cells
      exhibited induction of Bcl-2 protein expression, and RNA interference of Bcl-2 in
      this cell line resulted in augmentation of BITC-induced apoptosis. The BITC
      mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with
      the induction of PUMA protein in the tumor. In conclusion, the results of the
      present study indicate that Bim-independent apoptosis by BITC in cancer cells is
      mediated by PUMA.

PMID- 22359676
TI  - Antifibrinolytic role of a bee venom serine protease inhibitor that acts as a
      plasmin inhibitor.
AB  - Bee venom is a rich source of pharmacologically active substances. In this study,
      we identified a bumblebee (Bombus ignitus) venom Kunitz-type serine protease
      inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable
      inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In
      contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an
      antifibrinolytic agent; however, this inhibitory ability was two-fold weaker than
      that of aprotinin. The fibrin(ogen)olytic activities of B. ignitus venom serine
      protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI
      targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel
      mechanism by which bumblebee venom affects the hemostatic system through the
      antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated
      fibrin(ogen)olytic activities, raising interest in Bi-KTI and Bi-VSP as potential
      clinical agents.

PMID- 22359677
TI  - Insights into the transposable mobilome of Paracoccus spp. (Alphaproteobacteria).
AB  - Several trap plasmids (enabling positive selection of transposition events) were
      used to identify a pool of functional transposable elements (TEs) residing in
      bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25
      strains representing 20 species of this genus led to the capture and
      characterization of (i) 37 insertion sequences (ISs) representing 9 IS families
      (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite
      transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family)
      containing two predicted genetic modules, involved in the arginine deiminase
      pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite
      transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance
      and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g.
      Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to
      contain strong promoters able to drive transcription of genes placed downstream
      of the target site of transposition. Through the application of trap plasmid
      pCM132TC, containing a promoterless tetracycline resistance reporter gene, we
      identified five ways in which transposition can supply promoters to
      transcriptionally silent genes. Besides highlighting the diversity and specific
      features of several TEs, the analyses performed in this study have provided novel
      and interesting information on (i) the dynamics of the process of transposition
      (e.g. the unusually high frequency of transposition of TnPpa1) and (ii)
      structural changes in DNA mediated by transposition (e.g. the generation of large
      deletions in the recipient molecule upon transposition of ISPve1 of the IS21
      family). We also demonstrated the great potential of TEs and transposition in the
      generation of diverse phenotypes as well as in the natural amplification and
      dissemination of genetic information (of adaptative value) by horizontal gene
      transfer, which is considered the driving force of bacterial evolution.

PMID- 22359678
TI  - Intercellular transport of Oct4 in mammalian cells: a basic principle to expand a
      stem cell niche?
AB  - BACKGROUND: The octamer-binding transcription factor 4 (Oct4) was originally
      described as a marker of embryonic stem cells. Recently, the role of Oct4 as a
      key regulator in pluripotency was shown by its ability to reprogram somatic cells
      in vitro, either alone or in concert with other factors. While artificial
      induction of pluripotency using transcription factors is possible in mammalian
      cell culture, it remains unknown whether a potential natural transfer mechanism
      might be of functional relevance in vivo. The stem cell based regeneration of
      deer antlers is a unique model for rapid and complete tissue regeneration in
      mammals and therefore most suitable to study such mechanisms. Here, the transfer
      of pluripotency factors from resident stem cell niche cells to differentiated
      cells could recruit more stem cells and start rapid tissue regeneration.
      METHODOLOGY/PRINCIPAL FINDINGS: We report on the ability of STRO-1(+) deer
      antlerogenic mesenchymal stem cells (DaMSCs) to transport Oct4 via direct cell-to
      cell connections. Upon cultivation in stem cell expansion medium, we observed
      nuclear Oct4 expression in nearly all cells. A number of these cells exhibit Oct4
      expression not only in the nucleus, but also with perinuclear localisation and
      within far-ranging intercellular connections. Furthermore, many cells showed
      intercellular connections containing both F-actin and alpha-tubulin and through
      which transport could be observed. To proof that intercellular Oct4-transfer has
      functional consequences in recipient cells we used a co-culture approach with
      STRO-1(+) DaMSCs and a murine embryonic fibroblast indicator cell line (Oct4-GFP
      MEF). In this cell line a reporter gene (GFP) under the control of an Oct4
      responsive element is only expressed in the presence of Oct4. GFP expression in
      Oct4-GFP cells started after 24 hours of co-culture providing evidence of Oct4
      transfer from STRO-1(+) DaMSCs to Oct4-GFP MEF target cells. CONCLUSIONS: Our
      findings indicate a possible mechanism for the expansion of a resident stem cell
      niche by induction of pluripotency in surrounding non-niche cells via transfer of
      transcription factors through intercellular connections. This provides a new
      approach to explain the rapid annual antler regrowth.

PMID- 22359679
TI  - Genome organization, phylogenies, expression patterns, and three-dimensional
      protein models of two acetylcholinesterase genes from the red flour beetle.
AB  - Since the report of a paralogous acetylcholinesterase (AChE, EC3.1.1.7) gene in
      the greenbug (Schizaphis graminum) in 2002, two different AChE genes (Ace1 and
      Ace2) have been identified in each of at least 27 insect species. However, the
      gene models of Ace1 and Ace2, and their molecular properties have not yet been
      comprehensively analyzed in any insect species. In this study, we sequenced the
      full-length cDNAs, computationally predicted the corresponding three-dimensional
      protein models, and profiled developmental stage and tissue-specific expression
      patterns of two Ace genes from the red flour beetle (Tribolium castaneum; TcAce1
      and TcAce2), a globally distributed major pest of stored grain products and an
      emerging model organism. TcAce1 and TcAce2 encode 648 and 604 amino acid
      residues, respectively, and have conserved motifs including a choline-binding
      site, a catalytic triad, and an acyl pocket. Phylogenetic analysis show that both
      TcAce genes are grouped into two insect Ace clusters and TcAce1 is completely
      diverged from TcAce2, suggesting that these two genes evolve from their
      corresponding Ace gene lineages in insect species. In addition, TcAce1 is located
      on chromosome 5, whereas TcAce2 is located on chromosome 2. Reverse transcription
      polymerase chain reaction (PCR) and quantitative real-time PCR analyses indicate
      that both genes are virtually transcribed in all the developmental stages and
      predominately expressed in the insect brain. Our computational analyses suggest
      that the TcAce1 protein is a robust acetylcholine (ACh) hydrolase and has
      susceptibility to sulfhydryl agents whereas the TcAce2 protein is not a
      catalytically efficient ACh hydrolase.

PMID- 22359680
TI  - Fin-tail coordination during escape and predatory behavior in larval zebrafish.
AB  - Larval zebrafish innately perform a suite of behaviors that are tightly linked to
      their evolutionary past, notably escape from threatening stimuli and pursuit and
      capture of prey. These behaviors have been carefully examined in the past, but
      mostly with regard to the movements of the trunk and tail of the larvae. Here, we
      employ kinematics analyses to describe the movements of the pectoral fins during
      escape and predatory behavior. In accord with previous studies, we find roles for
      the pectoral fins in slow swimming and immediately after striking prey. We find
      novel roles for the pectoral fins in long-latency, but not in short-latency C
      bends. We also observe fin movements that occur during orienting J-turns and S
      starts that drive high-velocity predatory strikes. Finally, we find that the use
      of pectoral fins following a predatory strike is scaled to the velocity of the
      strike, supporting a role for the fins in braking. The implications of these
      results for central control of coordinated movements are discussed, and we hope
      that these results will provide baselines for future analyses of cross-body
      coordination using mutants, morphants, and transgenic approaches.

PMID- 22359681
TI  - Fluctuating environments, sexual selection and the evolution of flexible mate
      choice in birds.
AB  - Environmentally-induced fluctuation in the form and strength of natural selection
      can drive the evolution of morphology, physiology, and behavior. Here we test the
      idea that fluctuating climatic conditions may also influence the process of
      sexual selection by inducing unexpected reversals in the relative quality or
      sexual attractiveness of potential breeding partners. Although this phenomenon,
      known as 'ecological cross-over', has been documented in a variety of species, it
      remains unclear the extent to which it has driven the evolution of major
      interspecific differences in reproductive behavior. We show that after
      controlling for potentially influential life history and demographic variables,
      there are significant positive associations between the variability and
      predictability of annual climatic cycles and the prevalence of infidelity and
      divorce within populations of a taxonomically diverse array of socially
      monogamous birds. Our results are consistent with the hypothesis that
      environmental factors have shaped the evolution of reproductive flexibility and
      suggest that in the absence of severe time constraints, secondary mate choice
      behaviors can help prevent, correct, or minimize the negative consequences of
      ecological cross-overs. Our findings also illustrate how a basic evolutionary
      process like sexual selection is susceptible to the increasing variability and
      unpredictability of climatic conditions that is resulting from climate change.

PMID- 22359682
TI  - Removal of hepatitis C virus-infected cells by a zymogenized bacterial toxin.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and
      has become a global health threat. No HCV vaccine is currently available and
      treatment with antiviral therapy is associated with adverse side effects.
      Moreover, there is no preventive therapy for recurrent hepatitis C post liver
      transplantation. The NS3 serine protease is necessary for HCV replication and
      represents a prime target for developing anti HCV therapies. Recently we
      described a therapeutic approach for eradication of HCV infected cells that is
      based on protein delivery of two NS3 protease-activatable recombinant toxins we
      named "zymoxins". These toxins were inactivated by fusion to rationally designed
      inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3
      protease is present, the inhibitory peptide is removed resulting in re-activation
      of cytotoxic activity. The zymoxins we described suffered from two limitations:
      they required high levels of protease for activation and had basal activities in
      the un-activated form that resulted in a narrow potential therapeutic window.
      Here, we present a solution that overcame the major limitations of the "first
      generation zymoxins" by converting MazF ribonuclease, the toxic component of the
      E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin
      that is introduced to cells by means of gene delivery. We constructed an
      expression cassette that encodes for a single polypeptide that incorporates both
      the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3
      cleavable linker. While covalently paired to its inhibitor, the ribonuclease is
      well tolerated when expressed in naive, healthy cells. In contrast, activating
      proteolysis that is induced by even low levels of NS3, results in an eradication
      of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a
      valuable tool in eradicating cells infected by intracellular pathogens that
      express intracellular proteases.

PMID- 22359683
TI  - Fourier transform infrared spectroscopic imaging and multivariate regression for
      prediction of proteoglycan content of articular cartilage.
AB  - Fourier Transform Infrared (FT-IR) spectroscopic imaging has been earlier applied
      for the spatial estimation of the collagen and the proteoglycan (PG) contents of
      articular cartilage (AC). However, earlier studies have been limited to the use
      of univariate analysis techniques. Current analysis methods lack the needed
      specificity for collagen and PGs. The aim of the present study was to evaluate
      the suitability of partial least squares regression (PLSR) and principal
      component regression (PCR) methods for the analysis of the PG content of AC.
      Multivariate regression models were compared with earlier used univariate methods
      and tested with a sample material consisting of healthy and enzymatically
      degraded steer AC. Chondroitinase ABC enzyme was used to increase the variation
      in PG content levels as compared to intact AC. Digital densitometric measurements
      of Safranin O-stained sections provided the reference for PG content. The results
      showed that multivariate regression models predict PG content of AC significantly
      better than earlier used absorbance spectrum (i.e. the area of carbohydrate
      region with or without amide I normalization) or second derivative spectrum
      univariate parameters. Increased molecular specificity favours the use of
      multivariate regression models, but they require more knowledge of chemometric
      analysis and extended laboratory resources for gathering reference data for
      establishing the models. When true molecular specificity is required, the
      multivariate models should be used.

PMID- 22359685
TI  - The VersaJet for Breast-Reduction Surgery: Operator Beware.
AB  - BACKGROUND: Modern techniques for breast-reduction surgery depend on large
      surface de-epithelialization. The current gold standard technique involves the
      use of a scalpel for sharp debridement and is a time-consuming process that is
      labor-intensive and often requires an assistant to stabilize the breast. Surgeons
      who perform breast-reduction surgery continue to search for instruments and
      innovations that may reduce the time and effort required for successful de
      epithelialization. One such innovation is the use of the VersaJet Hydrosurgery
      system. The purpose of this article is to highlight an important complication
      that may result from the use of this device. METHODS: The authors describe their
      experience with the VersaJet Hydrosurgery System in reduction mammoplasty of 28
      breasts. RESULTS: The authors experienced several complications characterized by
      the formation of epithelial inclusion cysts requiring reoperation. CONCLUSION:
      The VersaJet Hydrosurgery system may lead to quicker speeds of de
      epithelialization as compared with traditional methods but poses a risk of
      epidermal cyst formation.

PMID- 22359684
TI  - Upregulation of UCP2 by adiponectin: the involvement of mitochondrial superoxide
      and hnRNP K.
AB  - BACKGROUND: The adipocyte-derived hormone adiponectin elicits protective
      functions against fatty liver diseases and hepatic injuries at least in part by
      stimulating the expression of a mitochondrial inner membrane transporter,
      uncoupling protein 2 (UCP2). The present study was designed to investigate the
      cellular and molecular mechanisms underlying adiponectin-induced UCP2 expression.
      METHODOLOGY/PRINCIPAL FINDINGS: Mice were treated with adiponectin and/or
      different drug inhibitors. Parenchymal (PCs) and nonparenchymal (NPCs) cells were
      fractionated from the liver tissues for mitochondria isolation, Western blotting
      and quantitative PCR analysis. Mitochondrial superoxide production was monitored
      by MitoSOX staining and flow cytometry analysis. Compared to control mice, the
      expression of UCP2 was significantly lower in NPCs, but not PCs of adiponectin
      knockout mice (AKO). Both chronic and acute treatment with adiponectin
      selectively increased the mRNA and protein abundance of UCP2 in NPCs, especially
      in the enriched endothelial cell fractions. The transcription inhibitor
      actinomycin D could not block adiponectin-induced UCP2 expression, whereas the
      protein synthesis inhibitor cycloheximide inhibited the elevation of UCP2 protein
      but not its mRNA levels. Mitochondrial content of heterogeneous nuclear
      ribonucleoprotein K (hnRNP K), a nucleic acid binding protein involved in
      regulating mRNA transportation and stabilization, was significantly enhanced by
      adiponectin, which also evoked a transient elevation of mitochondrial superoxide.
      Rotenone, an inhibitor of mitochondrial respiratory complex I, abolished
      adiponectin-induced superoxide production, hnRNP K recruitment and UCP2
      expression. CONCLUSIONS/SIGNIFICANCE: Mitochondrial superoxide production
      stimulated by adiponectin serves as a trigger to initiate the translocation of
      hnRNP K, which in turn promotes UCP2 expressions in liver.

PMID- 22359686
TI  - A classification system in the massive weight loss patient based on skin lesions
      and activity of daily living.
AB  - OBJECTIVE: Massive weight loss patients frequently have recalcitrant skin rashes
      and/or infections in the abdominal region and interference with activities of
      daily living (ADL) due to the redundant abdominal tissues. MATERIALS AND METHODS:
      A classification of these functional problems is described on the basis of the
      authors' experience with 75 consecutive massive weight loss patients undergoing
      surgery between March 2006 and August 2010. Patients are classified in 3 types.
      Type I: Chronic skin problems confined to the lower abdomen under the pannus
      and/or the skin folds of redundant pannus (+/- posterior lower torso). Type II:
      Chronic skin problems around the navel and/or under a secondary pannus in the
      mid/upper abdomen in addition to those observed in type I. Type III: Abdominal
      pannus and/or secondary roll in the abdomen with no chronic skin problems. These
      3 types are further categorized on the basis of the abdominal pannus size and
      associated ADL interference by the subtypes: (A) those with a small pannus and no
      ADL interference (B) for the large excessive pannus and ADL interference.
      RESULTS: Fifty-two patients (70%) were classified as type I. Fifteen patients
      (20%) were type II. Only 8 patients (10%) had no skin problems. Overall
      complication rate was 21%. Mean follow-up was 13.3 months postoperatively.
      CONCLUSIONS: The classification system is proposed to provide a practical method
      by which to categorize massive weight loss patients based upon the presence and
      location of skin problems and ADL interference. Surgical guidelines to address
      these functional requirements are presented on the basis of the classification
      system.

PMID- 22359687
TI  - A Contractile Network of Interstitial Cells of Cajal in the Supratarsal Mueller's
      Smooth Muscle Fibers With Sparse Sympathetic Innervation.
AB  - BACKGROUND: We previously reported that the supratarsal Mueller's muscle is
      innervated by both sympathetic efferent fibers and trigeminal proprioceptive
      afferent fibers, which function as mechanoreceptors-inducing reflexive
      contractions of both the levator and frontalis muscles. Controversy still
      persists regarding the role of the mechanoreceptors in Mueller's muscle;
      therefore, we clinically and histologically investigated Mueller's muscle.
      METHODS: We evaluated the role of phenylephrine administration into the upper
      fornix in contraction of Mueller's smooth muscle fibers and how intraoperative
      stretching of Mueller's muscle alters the degree of eyelid retraction in 20
      patients with aponeurotic blepharoptosis. In addition, we stained Mueller's
      muscle in 7 cadavers with antibodies against alpha-smooth muscle actin, S100,
      tyrosine hydroxylase, c-kit, and connexin 43. RESULTS: Maximal eyelid retraction
      occurred approximately 3.8 minutes after administration of phenylephrine and
      prolonged eyelid retraction for at least 20 minutes after administration.
      Intraoperative stretching of Mueller's muscle increased eyelid retraction due to
      its reflexive contraction. The tyrosine hydroxylase antibody sparsely stained
      postganglionic sympathetic nerve fibers, whereas the S100 and c-kit antibodies
      densely stained the interstitial cells of Cajal (ICCs) among Mueller's smooth
      muscle fibers. A connexin 43 antibody failed to stain Mueller's muscle.
      CONCLUSIONS: A contractile network of ICCs may mediate neurotransmission within
      Mueller's multiunit smooth muscle fibers that are sparsely innervated by
      postganglionic sympathetic fibers. Interstitial cells of Cajal may also serve as
      mechanoreceptors that reflexively contract Mueller's smooth muscle fibers,
      forming intimate associations with intramuscular trigeminal proprioceptive fibers
      to induce reflexive contraction of the levator and frontalis muscles.

PMID- 22359688
TI  - Intraorbital wooden foreign body.

PMID- 22359689
TI  - Field epidemiology in Africa.

PMID- 22359690
TI  - The genesis and evolution of the African Field Epidemiology Network.
AB  - In an effort to contain the frequently devastating epidemics in sub-Saharan
      Africa, the World Health Organization (WHO) Regional Office for Africa launched
      the Integrated Disease Surveillance and Response (IDSR) strategy in an effort to
      strengthen surveillance and response. However, 36 sub-Saharan African countries
      have been described as experiencing a human resource crisis by the WHO. Given
      this human resource situation, the challenge remains for these countries to
      achieve, among others, the health-related Millennium Development Goals (MDGs).
      This paper describes the process through which the African Field Epidemiology
      Network (AFENET) was developed, as well as how AFENET has contributed to
      addressing the public health workforce crisis, and the development of human
      resource capacity to implement IDSR in Africa. AFENET was established between
      2005 and 2006 as a network of Field Epidemiology Training Programs (FETPs) and
      Field Epidemiology and Laboratory Training Programs (FELTPs) in Africa. This
      resulted from an expressed need to develop a network that would advocate for the
      unique needs of African FETPs and FELTPs, provide service to its membership, and
      through which programs could develop joint projects to address the public health
      needs of their countries. A total of eight new programs have been developed in
      sub-Saharan Africa since 2006. Programs established after 2006 represent over 70%
      of current FETP and FELTP enrolment in Africa. In addition to growth in
      membership and programs, AFENET has recorded significant growth in external
      partnerships. Beginning with USAID, CDC and WHO in 2004-2006, a total of at least
      26 partners have been added by 2011. Drawing from lessons learnt, AFENET is now a
      resource that can be relied upon to expand public health capacity in Africa in an
      efficient and practical manner. National, regional and global health actors can
      leverage it to meet health-related targets at all levels. The AFENET story is one
      that continues to be driven by a clearly recognized need within Africa to develop
      a network that would serve public health systems development, looking beyond the
      founders, and using the existing capacity of the founders and partners to help
      other countries build capacity for IDSR and the International Health Regulations
      (IHR, 2005).

PMID- 22359691
TI  - The African Field Epidemiology Network--networking for effective field
      epidemiology capacity building and service delivery.
AB  - Networks are a catalyst for promoting common goals and objectives of their
      membership. Public Health networks in Africa are crucial, because of the severe
      resource limitations that nations face in dealing with priority public health
      problems. For a long time, networks have existed on the continent and globally,
      but many of these are disease-specific with a narrow scope. The African Field
      Epidemiology Network (AFENET) is a public health network established in 2005 as a
      non-profit networking alliance of Field Epidemiology and Laboratory Training
      Programs (FELTPs) and Field Epidemiology Training Programs (FETPs) in Africa.
      AFENET is dedicated to helping ministries of health in Africa build strong,
      effective and sustainable programs and capacity to improve public health systems
      by partnering with global public health experts. The Network's goal is to
      strengthen field epidemiology and public health laboratory capacity to contribute
      effectively to addressing epidemics and other major public health problems in
      Africa. AFENET currently networks 12 FELTPs and FETPs in sub-Saharan Africa with
      operations in 20 countries. AFENET has a unique tripartite working relationship
      with government technocrats from human health and animal sectors, academicians
      from partner universities, and development partners, presenting the Network with
      a distinct vantage point. Through the Network, African nations are making strides
      in strengthening their health systems. Members are able to: leverage resources to
      support field epidemiology and public health laboratory training and service
      delivery notably in the area of outbreak investigation and response as well as
      disease surveillance; by-pass government bureaucracies that often hinder and
      frustrate development partners; and consolidate efforts of different partners
      channelled through the FELTPs by networking graduates through alumni associations
      and calling on them to offer technical support in various public health
      capacities as the need arises. AFENET presents a bridging platform between
      governments and the private sector, allowing for continuity of health
      interventions at the national and regional level while offering free exit and
      entry for existing and new partners respectively. AFENET has established itself
      as a versatile networking model that is highly responsive to members' needs.
      Based on the successes recorded in AFENET's first 5 years, we envision that the
      Network's membership will continue to expand as new training programs are
      established. The lessons learned will be useful in initiating new programs and
      building sustainability frameworks for FETPs and FELTPs in Africa. AFENET will
      continue to play a role in coordinating, advocacy, and building capacity for
      epidemic disease preparedness and response.

PMID- 22359692
TI  - Central African Field Epidemiology and Laboratory Training Program: building and
      strengthening regional workforce capacity in public health.
AB  - The Central African Field Epidemiology and Laboratory Training Program (CAFELTP)
      is a 2-year public health leadership capacity building training program. It was
      established in October 2010 to enhance capacity for applied epidemiology and
      public health laboratory services in three countries: Cameroon, Central African
      Republic, and the Democratic Republic of Congo. The aim of the program is to
      develop a trained public health workforce to assure that acute public health
      events are detected, investigated, and responded to quickly and effectively. The
      program consists of 25% didactic and 75% practical training (field based
      activities). Although the program is still in its infancy, the residents have
      already responded to six outbreak investigations in the region, evaluated 18
      public health surveillance systems and public health programs, and completed 18
      management projects. Through these various activities, information is shared to
      understand similarities and differences in the region leading to new and
      innovative approaches in public health. The program provides opportunities for
      regional and international networking in field epidemiology and laboratory
      activities, and is particularly beneficial for countries that may not have the
      immediate resources to host an individual country program. Several of the
      trainees from the first cohort already hold leadership positions within the
      ministries of health and national laboratories, and will return to their
      assignments better equipped to face the public health challenges in the region.
      They bring with them knowledge, practical training, and experiences gained
      through the program to shape the future of the public health landscape in their
      countries.

PMID- 22359693
TI  - The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening
      public health systems and building human resource capacity.
AB  - The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a
      comprehensive two-year competency-based training and service program designed to
      build sustainable public health expertise and capacity. Established in 2009, the
      program is a partnership between the Ethiopian Federal Ministry of Health, the
      Ethiopian Health and Nutrition Research Institute, Addis Ababa University School
      of Public Health, the Ethiopian Public Health Association and the US Centers of
      Disease Control and Prevention. Residents of the program spend about 25% of their
      time undergoing didactic training and the 75% in the field working at program
      field bases established with the MOH and Regional Health Bureaus investigating
      disease outbreaks, improving disease surveillance, responding to public health
      emergencies, using health data to make recommendations and undertaking other
      field Epidemiology related activities on setting health policy. Residents from
      the first 2 cohorts of the program have conducted more than 42 outbreaks
      investigations, 27analyses of surveillance data, evaluations of 11 surveillance
      systems, had28oral and poster presentation abstracts accepted at 10 scientific
      conferences and submitted 8 manuscripts of which 2are already published. The
      EFELTP has provided valuable opportunities to improve epidemiology and laboratory
      capacity building in Ethiopia. While the program is relatively young, positive
      and significant impacts are assisting the country better detect and respond to
      epidemics and address diseases of major public health significance.

PMID- 22359694
TI  - One Health concept for strengthening public health surveillance and response
      through Field Epidemiology and Laboratory Training in Ghana.
AB  - The lack of highly trained field epidemiologists in the public health system in
      Ghana has been known since the 1970s when the Planning Unit was established in
      the Ghana Ministry of Health. When the Public Health School was started in 1994,
      the decision was taken to develop a 1 academic-year general MPH course. The
      persisting need for well-trained epidemiologists to support the public health
      surveillance, outbreak investigation and response system made the development of
      the Field Epidemiology and Laboratory Training Programme (FELTP) a national
      priority. The School of Public health and the Ministry of Health therefore
      requested the technical and financial assistance of the United States Centers for
      Disease Control and Prevention (CDC) in organizing the Programme. The
      collaboration started by organizing short courses in disease outbreak
      investigations and response for serving Ghana Health Service staff. The success
      of the short courses led to development of the FELTP. By October 2007, the new
      FELTP curriculum for the award of a Masters of Philosophy in Applied Epidemiology
      and Disease Control was approved by the Academic Board of the University of Ghana
      and the programme started that academic year. Since then five cohorts of 37
      residents have been enrolled in the two tracks of the programme. They consist of
      12 physicians, 12 veterinarians and 13 laboratory scientists. The first two
      cohorts of 13 residents have graduated. The third cohort of seven has submitted
      dissertations and is awaiting the results. The fourth cohort has started the
      second year of field placement while the fifth cohort has just started the first
      semester. The field activities of the graduates have included disease outbreak
      investigations and response, evaluation of disease surveillance systems at the
      national level and analysis of datasets on diseases at the regional level. The
      residents have made a total of 25 oral presentations and 39 poster presentations
      at various regional and global scientific conferences. The Ghana FELTP (GFELTP)
      has promoted the introduction of the One Health concept into FELTP. It hosted the
      first USAID-supported workshop in West Africa to further integrate and strengthen
      collaboration of the animal and human health sectors in the FETP model. GFELTP
      has also taken the lead in hosting the first AFENET Center for Training in Public
      Health Leadership and Management, through which the short course on Management
      for Improving Public Health Interventions was developed for AFENET member
      countries. The GFELTP pre-tested the Integrated Avian Influenza Outbreak and
      Pandemic Influenza course in preparation for introducing the materials into the
      curriculum of other FELTP in the network. The leadership positions to which the
      graduates of the program have been appointed in the human and animal Public
      Health Services, improvement in disease surveillance, outbreak investigation and
      response along with the testimony of the health authorities about their
      appreciation of the outputs of the graduates at various fora, is a strong
      indication that the GFELTP is meeting its objectives.

PMID- 22359695
TI  - The Rwanda Field Epidemiology and Laboratory Training Program: training skilled
      disease detectives.
AB  - Rwanda still suffers from communicable diseases which frequently lead to
      epidemics. In addition to other health workforce needs, Rwanda also lacks a
      public health workforce that can operate multi-disease surveillance and response
      systems at the national and sub-national levels.In 2009 and 2010 the Rwanda
      Ministry of Health and its partners from the Government of Rwanda (GOR) as well
      as the United States (US) Centers for Disease Control and Prevention, the African
      Field Epidemiology Network, and other partners embarked on a series of activities
      to develop a public health workforce that would be trained to operate disease
      surveillance and response systems at the national and district levels. The Rwanda
      Field Epidemiology and Laboratory Training Program (RFELTP) is a 2-year public
      health leadership development training program that provides applied epidemiology
      and public health laboratory training while the trainees provide public health
      service to the Ministry of Health. RFELTP is hosted at the National University of
      Rwanda School of Public Health for the didactic training. RFELTP is funded by
      GOR, the US Presidents Emergency Plan for AIDS Relief and the World Bank; it is
      managed by a multi-sectoral steering committee headed by the Minister of Health.
      The first RFELTP cohort has 15 residents who were recruited from key health
      programs in GOR. Over the first year of implementation, these 15 residents have
      conducted a variety of field investigations and responded to several outbreaks.
      RFELTP has also trained 145 frontline health workers through its two-week applied
      short courses. In the future, RFELTP plans to develop a veterinary track to
      address public health issues at the animal-human interface.

PMID- 22359696
TI  - Public health systems strengthening in Africa: the role of South Africa Field
      Epidemiology and Laboratory Training Programme.
AB  - The South Africa Field Epidemiology and Laboratory Training Programme (SAFELTP)
      was created in 2006 after recognizing the need to build and sustain the country's
      human resource capacity in field (applied) epidemiology and public health
      practice. The programme was formed as a collaboration between the South Africa
      Department of Health (DoH), the National Institute for Communicable Diseases
      (NICD), the National Health Laboratory Services (NHLS), the US Centers for
      Disease Control and Prevention (CDC) and the University of Pretoria. The primary
      goal of the programme was to produce field-trained epidemiologists equipped with
      knowledge and practical skills to effectively and efficiently address the public
      health priorities of South Africa. SAFELTP is a 2-year full-time training,
      consisting of a combination of classroom-based instruction (30%) and mentored
      field work (70%). The training places emphasis on public health surveillance,
      investigation of disease epidemics, public health laboratory practice and
      communication of epidemiologic information, among other aspects of epidemiology
      research. At completion, residents are awarded a Master of Public Health (MPH)
      degree from the University of Pretoria. Since its inception in 2006, 48 residents
      have enrolled onto the programme and 30 (62%) of them have completed the
      training. Over the past 5 years, the residents have conducted more than 92
      outbreak investigations, 47 surveillance evaluations, 19 planned studies,
      analyzed 37 large databases and presented more than 56 papers at local and
      international conferences. In recognition of the high-quality work, at least five
      SAFELTP residents have received awards at various international scientific
      conferences during the 5 years. In conclusion, the South Africa FELTP is now
      fully established and making valuable contributions to the country's public
      health system, albeit with innumerable challenges.

PMID- 22359697
TI  - The Tanzania Field Epidemiology and Laboratory Training Program: building and
      transforming the public health workforce.
AB  - The Tanzania Field Epidemiology and Laboratory Training Program (TFELTP) was
      established in 2008 as a partnership among the Ministry of Health and Social
      Welfare (MOHSW), Muhimbili University of Health and Allied Sciences, National
      Institute for Medical Research, and local and international partners. TFELTP was
      established to strengthen the capacity of MOHSW to conduct public health
      surveillance and response, manage national disease control and prevention
      programs, and to enhance public health laboratory support for surveillance,
      diagnosis, treatment and disease monitoring. TFELTP is a 2-year full-time
      training program with approximately 25% time spent in class, and 75% in the
      field. TFELTP offers two tracks leading to an MSc degree in either Applied
      Epidemiology or, Epidemiology and Laboratory Management. Since 2008, the program
      has enrolled a total of 33 trainees (23 males, 10 females). Of these, 11 were
      enrolled in 2008 and 100% graduated in 2010. All 11 graduates of cohort 1 are
      currently employed in public health positions within the country. Demand for the
      program as measured by the number of applicants has grown from 28 in 2008 to 56
      in 2011. While training the public health leaders of the country, TFELTP has also
      provided essential service to the country in responding to high-profile disease
      outbreaks, and evaluating and improving its public health surveillance systems
      and diseases control programs. TFELTP was involved in the country assessment of
      the revised International Health Regulations (IHR) core capabilities, development
      of the Tanzania IHR plan, and incorporation of IHR into the revised Tanzania
      Integrated Disease Surveillance and Response (IDSR) guidelines. TFELTP is
      training a competent core group of public health leaders for Tanzania, as well as
      providing much needed service to the MOHSW in the areas of routine surveillance,
      outbreak detection and response, and disease program management. However, the
      immediate challenges that the program must address include development of a full
      range of in-country teaching capacity for the program, as well as a career path
      for graduates.

PMID- 22359698
TI  - The West Africa Field Epidemiology and Laboratory Training Program, a strategy to
      improve disease surveillance and epidemic control in West Africa.
AB  - The West Africa Field Epidemiology and Laboratory Training Program (WA-FELTP)
      which was established in September 2007, is an inter-country, competency-based,
      in-service and post -graduate training program in applied epidemiology and public
      health that builds the capacity to strengthen the surveillance and response
      system as well as epidemic control in the French-speaking countries where they
      are implemented. The overall purpose is to provide epidemiological and public
      health laboratory services to the public health systems at national, provincial,
      district and local levels. The program includes four countries: Burkina Faso,
      Mali, Niger, and Togo with an overarching goal to progressively cover all French
      speaking countries in West Africa through a phased-in approach. WA-FELTP's 2-
      year Master's program was launched in 2010 with 12 residents, three from each
      country, and consists of medical and veterinary doctors, pharmacists, and
      laboratory scientists. The training comprises 25% didactic sessions and 75%
      practical in-the-field mentored training. During the practical training,
      residents rovide service to their respective ministries of health and ministries
      of animal resources by contributing to outbreak investigations and activities
      that help to improve national surveillance systems at national, regional,
      district and local levels. The pressing challenges that the program must address
      consist of the lack of funds to support the second cohort of trainees, though
      trainee selection was completed, inadequate funds to support staff compensation,
      and shortage of funds to support trainees' participation in critical activities
      in field epidemiology practice, and a need to develop a 5-year plan for
      sustainability.

PMID- 22359699
TI  - Two decades of post-graduate training in applied public health: the experience
      and challenges of the Uganda Public Health School Without Walls.
AB  - The objective of this work is to describe the experience of the Uganda Public
      Health School Without Walls (PHSWOW) in training public health professionals at
      post-graduate level to offer leadership in planning, delivery of health services
      and research within a decentralized health system. As one of the constituents of
      the Makerere University College of Health Sciences, the Uganda PHSWOW has the
      vision of becoming a Centre of Excellence, providing leadership in public health
      and the mission of promoting the attainment of better health of the people in
      Uganda and beyond through public health training, research and community service.
      Key to the successes of the program are the 238 program graduates, most of whom
      have remained in-country to serve at district and national levels of service
      delivery. Collaborations have been established with government, private, non
      governmental and international institutions leading to increased health service
      provision and research for the improvement of health status of populations and
      influence on public policy. There is still a lot to do in diversifying the skills
      mix of graduates and contributing to an ambitious increment from 0.4 to 4.7
      public health professionals per 10,000 population; as is currently the case in
      high-middle income countries. Currently, the Uganda PHSWOW has exceeded the
      proposed output for FETPs of training 3 to 5 graduates per 1 million population
      suggested by some authors, however the output is still inadequate. More also
      needs to be done to promote a culture of publication in an effort to translate
      public health evidence into policy and practice.

PMID- 22359700
TI  - Strengthening field epidemiology in Africa: the Zimbabwe Field Epidemiology
      Training Program.
AB  - The Zimbabwe Masters in Public Health Program is a 2-year competency based
      training that consists of classroom teaching (30%) and on the job field training
      (70%). The MPH program was created in 1993 with the aim of assisting the Ministry
      of Health and Child Welfare create a permanent capacity to recruit, train, and
      employ public health practitioners to sustain the public health infrastructure.
      The MPH program is operated from two sites: the DCM at the College of Health
      Sciences, of University of Zimbabwe (UZ) and the Health Studies Office (HSO) in
      MOHCW. The HSO in the MOHCW oversees the operation of field training in
      collaboration with approved Field Supervisors at the training sites. MOHCW
      provides field training sites through its eight provincial medical directorates.
      In addition the health directorates of the major cities in the country are
      designated field training sites. Since 1993, the program has had 18 Cohorts
      trained of which three are part-time. The part-time program was initiated in 2008
      with an intake of 10 trainees. Since 2003, the full time program has experienced
      an increase in intake with the highest intake recorded being 16 trainees in 2003.
      The average intake from 2003 - 2011 has been 12 trainees. A total of 169 trainees
      have been enrolled in the last 19 years. Of the 143 trainees enrolled by 2009,
      136 (95%) have graduated. The part-time program has had one cohort graduating
      with 5 out 10 successfully completing the course. Since the launch of the
      program, the majority of the graduates have filled most of the key public health
      positions and even so the positions in most of the nongovernmental organisations.

PMID- 22359701
TI  - Paradigm shift: contribution of field epidemiology training in advancing the "One
      Health" approach to strengthen disease surveillance and outbreak investigations
      in Africa.
AB  - The occurrence of major zoonotic disease outbreaks in Sub-Saharan Africa has had
      a significant impact on the already constrained public health systems. This has,
      as a result, justified the need to identify creative strategies to address
      threats from emerging and re-emerging infectious diseases at the human-animal
      environmental interface, and implement robust multi-disease public health
      surveillance systems that will enhance early detection and response.
      Additionally, enhanced reporting and timely investigation of all suspected
      notifiable infectious disease threats within the health system is vital. Field
      epidemiology and laboratory training programs (FELTPs) have made significant
      contributions to public health systems for more than 10 years by producing highly
      skilled field epidemiologists. These epidemiologists have not only improved
      disease surveillance and response to outbreaks, but also improved management of
      health systems. Furthermore, the FETPs/FELTPs have laid an excellent foundation
      that brings clinicians, veterinarians, and environmental health professionals
      drawn from different governmental sectors, to work with a common purpose of
      disease control and prevention. The emergence of the One Health approach in the
      last decade has coincided with the present, paradigm, shift that calls for multi
      sectoral and cross-sectoral collaboration towards disease surveillance,
      detection, reporting and timely response. The positive impact from the
      integration of FETP/FELTP and the One Health approach by selected programs in
      Africa has demonstrated the importance of multi-sectoral collaboration in
      addressing threats from infectious and non- infectious causes to man, animals and
      the environment.

PMID- 22359702
TI  - Public health laboratory systems development in East Africa through training in
      laboratory management and field epidemiology.
AB  - Laboratories are integral to the delivery of quality health care and for public
      health functions; however laboratory systems and services are often neglected in
      resource-poor settings such as the East African region. In order to sustainably
      strengthen national laboratory systems in resource-poor countries, there is a
      need to train laboratory personnel to work in clinical as well as public health
      laboratories. In 2004,Kenya, Uganda, Tanzania, and South Sudan began training
      public health laboratory workers jointly with field epidemiologists in the Kenya
      Field Epidemiology and Laboratory Training Program (FELTP), and later through the
      Tanzania FELTP, as a strategy to strengthen public health laboratories. These
      programs train laboratory epidemiologists through a two-year public health
      leadership development course, and also offer various types of short course
      training for frontline staff. The FELTP laboratory graduates in Kenya, Tanzania,
      Uganda, and South Sudan are working in their respective countries to strengthen
      public health laboratory systems while the short course participants provide a
      pool of frontline implementers with the capacity to support the lower tiers of
      health systems, as well as serve as surge capacity for the regions and the
      national level. Through training competent public health laboratory workers, the
      East African ministries of health, in collaboration with other regional partners
      and stakeholders are now engaged in developing and implementing a holistic
      approach that will guarantee an overall strengthening of the health system by
      using well-trained public health laboratory leaders to drive the process.
      Strengthening public health laboratory medicine in East Africa is critical to
      improve health-care systems. The experience with the FELTP model in East Africa
      is a step in the right direction towards ensuring a stronger role for the
      laboratory in public health.

PMID- 22359703
TI  - Continuity of care and quality of care - inseparable twin.

PMID- 22359704
TI  - Delirium in the elderly: a review.
AB  - Delirium is a common disorder, often under diagnosed and mismanaged. It is
      becoming more prevalent, because of the ageing population. In this clinical
      review, we summarise the definition, diagnosis and management of delirium.

PMID- 22359705
TI  - Clinical characteristics of childhood guillain-barre syndrome.
AB  - OBJECTIVES: To find the incidence, clinical pattern and outcome of Guillain-Barre
      syndrome in the Sultanate of Oman in children less than 15 years of age. METHODS:
      All children under fifteen years with acute flaccid paralysis were admitted to
      identify the underlying cause. The diagnosis of Gullain Barre syndrome was made
      by clinical criteria, cerebrospinal fluid findings and nerve conduction studies.
      Intravenous immunoglobulins were given to all and two needed plasmapharesis.
      RESULTS: Sixty-one children were diagnosed as Guillan-Barre syndrome and
      constituted 20% of cases of acute flaccid paralysis. Males 39 (63.9%) outnumbered
      females (36.1%).The annual incidence below 15 years was 0.45/100,000. Cranial
      nerves were involved in 31 (50.8%) children. Albumino-cytological dissociation in
      cerebrospinal fluid was seen in 42/45(93.3%) cases. Acute relapse was seen in six
      (9.8%) cases. Eleven children (18.3%) needed ventilation. Complete recovery was
      seen in 45 to 310 days (mean 69.1 days). Three children (4.9%) were left with
      minimal residual deficit. There was no mortality. CONCLUSIONS: Guillain Barre
      syndrome is a serious disease, although recovery is the rule in children. The
      disease is associated with very low mortality and long term morbidity.
      Immunoglobulins have reduced the duration of hospital stay and the total time
      needed for recovery.

PMID- 22359706
TI  - Management of penile fracture.
AB  - OBJECTIVES: To study clinical features and treatment of patients diagnosed with
      fractured penis. METHODS: All patients diagnosed with penis fracture from March
      2000-March 2007 were retrospectively studied. No invasive investigation was used
      for diagnosis. RESULTS: Surgical intervention was done in 52 patients while 5
      patients were managed conservatively. The constant finding recorded in all cases
      was that penis fracture occurred in erect penises. Most fractures were observed
      in the 16-30 years age group (50.88%). Left lateral tear was present in 53.84%
      cases. One patient had gangrene of penile skin after surgery. CONCLUSION: Penis
      Fracture is not so uncommon as reported. A trauma to erect penis is mandatory for
      fracture to occur. Surgical intervention is the preferred mode of treatment.

PMID- 22359707
TI  - Laparoscopic assisted two port open appendicectomy.
AB  - OBJECTIVES: The laparoscopic appendicectomy can be performed using one to several
      ports. We present our experience of two port laparoscopic assisted open
      appendicectomy. The objective was to assess the results retrospectively in terms
      of complications and its limitations. METHODS: Between years 1998-2007, a two
      port laparoscopic assisted appendectomy was attempted in 2380 adult patients with
      suspected appendicitis. The patients with localized or generalized peritonitis
      were included. The appendicectomy was performed via an assisted two port method
      using 10 mm umbilical optical port and another 10 mm port in right iliac fossa.
      The children aged 12 and below and pregnant patients were excluded. All patients
      had their laparoscopic appendicectomy within 48 hours of admission. RESULTS: Two
      port laparoscopic assisted appendicectomy was successful in 86.9% of cases. Acute
      appendicitis was the cause of acute abdomen in 88.9% of the patients. The
      accessory port was required in 8.5% of patients to complete the appendicectomy
      and the conversion rate to open was 4.6%. The mean operation time was 25 minutes
      and the mean hospital stay was 1.5 days. The port site infection was seen in 14,
      bleeding in 20, parietal wall abscess in three cases and intra-abdominal
      abscesses in 4 patients. CONCLUSION: This approach is simple, can be converted to
      total intracorporeal by inserting accessory port or to open appendicectomy when
      required and has advantage of full laparoscopy of abdomen. It has its limitations
      in cases of extreme obesity, thick mesentery, gangrenous appendix, very large and
      thick appendix, and difficulty in finding the appendix, control of bleeding,
      division of adhesions and to deal with other associated pathology. Cost was
      minimized by using non-disposable port. The overall morbidity was low. There were
      no specific complications related to this technique and incidence of port site
      infection was similar to other approaches of laparoscopic appendicectomy.

PMID- 22359708
TI  - Hemoglobin A1c in Muscat, Oman - A 3 year study.
AB  - BACKGROUND: Glycosylated Hemoglobin (HbA1c) reflects the average blood glucose
      level during the previous 2-3 months. HbA1c is used as marker for long term blood
      glucose control in diabetic patients. In this retrospective study, the prevalence
      of diabetic control was evaluated from HbA1c tests of diabetic patients over a
      period of 3 years (January 2005-December 2007) from Muscat Region, Sultanate of
      Oman. Blood samples from a total number of 7442 patients were analysed at Al
      Nahdha Hospital Laboratory received from different Primary Health Care Centers
      and Hospitals of Muscat region as this hospital was the referral hospital for
      HbA1c testing. METHODS: The method used for the estimation of HbA1c was
      Turbidimetric inhibition immunoassay and the test was carried out in Hitachi 902
      an automated chemistry analyzer. RESULTS: The results show that only 22.8% of
      patients had good glycemic control and 77.2% had bad glycemic control.
      CONCLUSION: Diabetic patients should be informed of the fact that maintaining
      HbA1c below 7% will minimize their risk of developing the complications.

PMID- 22359709
TI  - Susceptibilities of common bacterial isolates from oman to old and new
      antibiotics.
AB  - OBJECTIVES: The purpose of this study is to compare the antimicrobial activity of
      linezolid and tigecycline with other commonly used antibiotics against a variety
      of clinical isolates at Royal Hospital, Muscat. METHODS: Clinically-significant
      bacterial isolates in Royal hospital during the period from 1st of March to 30th
      of June 2007 were collected, stored and finally tested to determine their
      susceptibility to different antibiotics by broth microdilution (microscan
      panels). RESULTS: Two hundred ten bacterial strains were collected and tested
      including Staphylococcus aureus (29), Group B beta-haemolytic Streptococcus (10),
      Streptococcus pneumoniae (15), Enterococcus spp. (16), Haemophilus spp. (15),
      Escherichia coli (26), Klebsiella spp. (26), Enterobacter spp. (25), Serratia
      spp. (10), Acinetobacter baumannii (17) and Pseudomonas aeruginosa (21). All
      strains except P. aeuginosa were susceptible to tigecycline. All gram-positive
      strains were susceptible to linezolid. Meropenem and piperacillin-tazobactam
      showed good activity against most organisms tested including P. aeruginosa and
      Acinetobacter baumannii. Levofloxacin showed 100% activity against K. pneumoniae
      and 61% activity against E. coli. The activity of 3rd generation cephalosporins
      against E.coli and K.pneumoniae ranged from 76% to 100%. CONCLUSION: Tigecycline
      and linezolid showed excellent activity against microorganisms in their relevant
      spectrum of activity. However, they should be used wisely and judiciously.

PMID- 22359710
TI  - Strategic approach to improving maternal survival in oman.
AB  - THIS STUDY OF MATERNAL MORTALITY IN OMAN TRIES TO ANSWER THE QUESTION: Is the
      Fifth Millennium Development Goal achievable in Oman or not? In Oman, Maternal
      Mortality Ratio currently stands at 22.9/100,000, a reduction of 38.9% from its
      37.5/100,000 in 2002. This figure suggests that much needs to be done to
      accelerate progress towards the achievement of the Fifth Millennium Development
      Goal. Characteristics of 135 Omani women who died during pregnancy, labour or
      puerperium during the period 1990-2005 were studied. Data related to maternal
      health in Oman were also scrutinized, e.g. age of first marriage, ante-natal,
      natal and post-natal care, birth spacing, fertility and perinatal mortality. The
      study calls for accelerated efforts and renewed commitment to maternal health and
      recommends a framework for national strategic directions to scale up access to
      essential interventions to reduce maternal mortality in Oman and move closer to
      the achievement of the Fifth Millennium Development Goal.

PMID- 22359711
TI  - Gastrointestinal bleeding in tetralogy of fallot.
AB  - This article reports an uncommon cause of gastrointestinal bleeding in a young
      male with uncorrected Tetralogy of Fallot (TOF). This is the first reported
      instance of gastrointestinal stromal tumor (GIST) causing bleeding in a patient
      with uncorrected TOF. A 32-year-old Caucasian male with severe developmental
      delay and uncorrected TOF presented with black tarry stools. On admission, the
      patient was hypotensive and tachycardic. He was successfully resuscitated with
      fluids and blood transfusion. Upper gastrointestinal endoscopy was performed and
      biopsy revealed GIST. It is interesting to note that the patient survived till
      this age without any medical or surgical treatment. This case presents GIST as a
      cause of gastrointestinal bleeding in uncorrected TOF. Cytogenetic analysis
      revealed deletion of short arm of chromosome 18. This case illustrates that
      tyrosine kinase inhibitor may be an acceptable alternative therapy to surgical
      resection.

PMID- 22359712
TI  - Non-hodgkin lymphoma mimicking polymyalgia rheumatica in a young patient.
AB  - Congenital nasal pyriform aperture stenosis (CNPAS) is a recently defined
      clinical entity that causes airway obstruction in the neonate as a result of
      narrowing of the nasal pyriform aperture. The pyriform aperture is the narrowest,
      most anterior portion of the nasal airway, and a slight decrease in its cross
      sectional area will significantly increase the nasal airway resistance. This
      entity should be kept in the differential diagnosis of any neonate or infant with
      signs and symptoms of upper air way obstruction. The CNPAS presents with symptoms
      of nasal airway obstruction, which are often characterized by episodic apnea and
      cyclic cynosis.

PMID- 22359713
TI  - Congenital nasal pyriform aperture stenosis: first case report in oman.
AB  - Congenital nasal pyriform aperture stenosis (CNPAS) is a recently defined
      clinical entity that causes airway obstruction in the neonate as a result of
      narrowing of the nasal pyriform aperture. The pyriform aperture is the narrowest,
      most anterior portion of the nasal airway, and a slight decrease in its cross
      sectional area will significantly increase the nasal airway resistance. This
      entity should be kept in the differential diagnosis of any neonate or infant with
      signs and symptoms of upper air way obstruction. The CNPAS presents with symptoms
      of nasal airway obstruction, which are often characterized by episodic apnea and
      cyclic cynosis.

PMID- 22359714
TI  - Recurrent cervical stenosis - a troublesome clinical entity.
AB  - Cervical is a troublesome clinical problem. It usually follows surgery on cervix;
      also seen with endometrial and cervical malignancies. There is a high recurrence
      rate after the traditional treatment which is cervical dilatation. Various other
      treatment options have been tired. We report a case of recurrent cervical
      stenosis successfully treated with a different technique.

PMID- 22359715
TI  - Glucose Galactose Malabsorption complicated with Rickets and Nephrogenic Diabetes
      Insipidus.
AB  - Congenital Glucose Galactose malabsorption (CGGM) is a rare disorder with limited
      data from the Arab world. We report the first case of CGGM in Oman.B.S.A two
      years old female who presented with chronic osmotic diarrhea since birth with
      hypernatraemic dehydration. B.S was found to have Glucose Galactose Malabsorption
      based on clinical trial of ORS and elemental formula. Symptoms resolved on
      introduction of Carbohydrate free formula. The patient developed many
      complications while on TPN including rickets and nephrogenic diabetes insipidus.
      These complications have not been reported earlier in CGGM.

PMID- 22359716
TI  - Thrombosis of bioprosthetic right atrioventicular valve in a patient with
      ?complex congenital heart disease clinical images.

PMID- 22359717
TI  - Early recognition and management of pulmonary arterial hypertension: a case for
      profiling.

PMID- 22359718
TI  - The establishment and roles of the Medical Education Department in the faculty of
      Medicine, King Abdul Aziz University, Jeddah Saudi Arabia.
AB  - Medical Education departments oversee the process of medical education in medical
      schools and provide many educational services to support, evaluate and thus
      enhance the educational role of the medical school. Its roles revolve around
      research, teaching and providing educational support in areas of curriculum
      development and assessment. This paper provides a brief summary on the emergence
      of different medical education centers/units/departments around the world from a
      historical perspective. Special attention will be given to the process followed
      in establishing the Medical Education Department (MED) in King Abdul Aziz
      University (KAU). This paper also explores the roles that are currently played
      within the department with a reflection on documented roles of the medical
      education departments worldwide. Special emphasis will be given to explore the
      current challenges faced by KAU MED and proposed suggestions to improve these
      challenges will also be addressed.

PMID- 22359719
TI  - Suppression of mycobacterium tuberculosis induced reactive oxygen species and
      tumor necrosis factor-alpha activity in human monocytes of systemic lupus
      erythematosus patients by reduced glutathione.
AB  - OBJECTIVES: The etiology and pathogenesis of systemic lupus erythematosus remains
      unknown, evidence exists for the involvement of mycobacterial antigen. This study
      is aimed to determine the effect of Mycobacterium tuberculosis on clinical course
      of SLE patients and the role of ROS and TNF-alpha in the pathogenesis of
      tuberculosis associated SLE patients. METHODS: This study was done on 100
      patients divided into SLE group (n=30), TB group (n=30), SLE-TB group (n=30) and
      control group (n=10). All patients underwent clinical, biochemical and
      immunological evaluation by employing techniques such as SDS-PAGE, direct binding
      and competition ELISA, PBMC and cell culture. RESULTS: Fever, arthritis, skin
      rash, photosensitivity were more common in both SLE and SLE-TB group. Reduced
      glutathione showed amelioration of ROS and TNF-alpha induced action, which in
      turn, subsequently suppressed the immune-bindings observed in monocytes of TB and
      SLE patients cultured without glutathione. CONCLUSION: Data shows that SLE
      patients are more susceptible to developing Mycobacterium tuberculosis, as ROS
      and TNF-alpha in SLE patients could activate the replication of mycobacterial
      Ag85B (30 kDa) after bacilli infection.

PMID- 22359720
TI  - Public knowledge, attitude and practice of complementary and alternative medicine
      in riyadh region, saudi arabia.
AB  - OBJECTIVES: Complementary and alternative medicine (CAM) is well established
      worldwide. The present work is aimed at studying the knowledge, attitude and
      practice of CAM by the people of Riyadh region, Saudi Arabia. METHODS: A cross
      sectional descriptive household survey study of the people living in Riyadh city,
      as well as the surrounding governorates. A multistage random sample was taken
      from 1(st) January to the end of March 2010, with a total number of 518
      participants. Data were collected using a pre-designed questionnaire through
      direct interview. The data was collected based on socio-demography, as well as
      knowledge, attitude and practice of CAM. RESULTS: Participants were nearly sex
      matched, consisting of approximately 70% Saudi and 30% non-Saudis. About 89% of
      the participants had some knowledge of CAM. Mass media e.g. (T.V., newspapers and
      radio) and family, relatives and friends represented the main sources of CAM
      knowledge, (46.5% and 46.3% respectively). Nearly 85% of participants or one of
      their family members has used some form of CAM before, and the most common users
      of CAM practices were females, housewives, and illiterate subjects (or those who
      could just read and write), as well as participants aged 60 years and above.
      Medical herbs (58.89%), prayer (54%), honey and bee products (54%), hijama
      (35.71%) and cauterization or medical massage therapy (22%) were the commonly
      used CAM practices. Most participants agreed that there are needs for; CAM
      practices (93.8%), regulations for CAM (94.9%), health education (96.6%),
      specialized centers (94.8%) and CAM clinics (92.7%). While only 8.3% of
      participants usually discussed CAM with their physicians. CONCLUSION: There is a
      high prevalence and increased public interest in CAM use in the Riyadh region.
      There is a positive attitude towards CAM, yet most participants are reluctant to
      share and discuss CAM information with their physicians.

PMID- 22359721
TI  - Effects of Losartan vs. Enalapril on the Markers of Metabolic Syndrome.
AB  - OBJECTIVE: To compare the effects of losartan and enalapril on the markers of
      metabolic syndrome. METHODS: One hundred and twenty six newly diagnosed
      hypertensive patients having other markers of metabolic syndrome participated in
      this study. The study was performed in the department of pharmacology, college of
      medicine at Ibn-Sina Teaching Hospital in Mosul city, Iraq, during the period
      between December 2007 and June 2009. The patients were divided into 2 main
      groups: 1) Losartan group: consisted of 60 patients, and 2) enalapril group:
      Consisted of 66 patients. Waist circumference, weight, Body mass index, blood
      pressure, serum glucose concentration, triglyceride and HDL-cholestrol were
      measured before and after administration of therapy. The effects of therapy were
      assessed by statistically comparing the results before and after the drug
      administration. RESULTS: Comparison of waist circumference, blood pressure, FSG,
      triglycerides of the patients before drug administration (baseline data), with
      those of the controls showed a significant elevation, while HDL-cholesterol
      showed a significant reduction. A significant reduction of waist circumference,
      BP, FSG and a significant elevation of HDL-cholesterol were also noted after
      therapy with both losartan and enalapril. CONCLUSION: Both losartan and enalapril
      produced a significant reduction of markers of metabolic syndrome and may be
      regarded as effective drugs for treatment of hypertension in patients with
      markers of metabolic syndrome.

PMID- 22359722
TI  - Asymptomatic bacteriuria in antenatal patients in ilorin, Nigeria.
AB  - OBJECTIVE: To determine the prevalence of asymptomatic bacteriuria, bacteriology
      and sensitivity pattern in Ilorin using the gold standard of urine culture.
      METHODS: A prospective study was carried out from 1st July to 31st October 2007,
      at the University of Ilorin Teaching Hospital (UITH) on 125 consenting
      asymptomatic pregnant women. A structured proforma was used to collect
      information from the women and a midstream urine specimen collected for
      bacteriological culture. RESULTS: Of the 125 pregnant women, 50 had bacteriuria
      on urine culture giving a prevalence of 40%. The mean age of the women was 28.5
      years with a standard deviation of 4.95. The age ranged between 14 and 40 years.
      Staphylococcus aureus was the commonest pathogen isolated (72%), followed by
      Proteus spp (14%). Most of the organisms showed good sensitivity to
      Nitrofurantoin and gentamicin. CONCLUSION: The prevalence of asymptomatic
      bacteriuria in Ilorin is high and routine urine culture is advocated for all
      pregnant women at booking.

PMID- 22359723
TI  - Extent of subclinical pulmonary involvement in childhood onset systemic lupus
      erythematosus in the sultanate of oman.
AB  - OBJECTIVES: The aim of this study was to investigate the frequency of pulmonary
      function abnormalities in clinically asymptomatic children with Systemic Lupus
      Erythematosus and to determine the relationship of these abnormalities to
      clinical, laboratory, and immunological parameters as well as to disease
      activity. METHODS: Forty-two children with childhood onset Systemic Lupus
      Erythematosus were included in this study. Demographic, clinical, laboratory and
      immunological parameters, as well as disease activity were assessed. Pulmonary
      function tests (PFT) were performed routinely to screen for subclinical lung
      disease. RESULTS: Out of the 42 children, 19% (n=8) had clinical evidence of
      pulmonary involvement. The patients with no clinical evidence of pulmonary
      involvement (n=34) represent the study cohort. From our cohort of patients with
      no clinical evidence of pulmonary involvement 79% (n=27) had PFT abnormality;
      including 62% (n=21) had reduced FVC, 71% (n=24) had reduced FEV1, and 67% (n=12)
      had reduced DLCO. Similarly, 56% (n=15) had a restrictive PFT pattern, and 2.6%
      (n=2) had an obstructive PFT pattern, while 33% (n=7) had an isolated impairment
      of diffusion capacity. Due to small sample size; it was not possible to find a
      statistically significant difference between the cohort of asymptomatic SLE
      patients with abnormal PFT findings (n=27) and those with normal PFT findings
      (n=7) in terms of clinical, laboratory, immunological or disease activity index
      score. CONCLUSION: Subclinical lung disease, as demonstrated by abnormal PFT in
      patients with normal radiographs, may be common but should be interpreted with
      caution as an early sign of lung disease. Although PFT studies do not correlate
      well with pulmonary symptoms in patients with childhood onset SLE, they
      nevertheless provide objective quantification of the type and severity of the
      functional lesions.

PMID- 22359724
TI  - Concentrations of Serum Zinc, Hemoglobin and Ferritin among Pregnant Women and
      their Effects on Birth Outcomes in Kashan, Iran.
AB  - OBJECTIVES: Zinc and Iron are essential micronutrients in fetus growth and
      development. The aim of this study was to assess the relationship of maternal
      serum Zinc, Hemoglobin and Ferritin levels with their newborns weight, height and
      head circumference. METHODS: This cross sectional-analytical study carried out
      among pregnant women referred to Naghavi Polyclinic, Kashan, Iran from November
      2009 to October 2010. One hundred and twenty-nine pregnant women in the third
      trimester were selected and anthropometric factors of their newborns (weight,
      height and head circumference) and their relation to serum Zn, Hemoglobin and
      Ferritin concentrations were assessed. RESULTS: Serum Hemoglobin deficiency
      (<11g/dl), serum Ferritin deficiency (<12 ug/L) and serum Zn deficiency (<66
      ug/dl) were present in 11 (8.5%), 9 (7%) and 9 (7%) women, respectively. The
      proportion of newborns with birth weight of 2500-2999 g was greater among mothers
      with lower Hemoglobin (<11 g/dl) compared to mothers with normal Hemoglobin (>=11
      g/dl; p=0.04). Multiple regression analysis showed that among biochemical
      characteristics of pregnant women, serum Hemoglobin levels were positively
      correlated with low birth weight (beta=0.26; p=0.04). But serum Zn and Ferritin
      levels were not significantly associated with weight, height and head
      circumference. CONCLUSION: Low maternal serum hemoglobin levels are associated
      with low birth weight and does not have any association with birth height or head
      circumference; but there was no significant association between maternal serum
      zinc and Ferritin levels with weight, height and head circumference.

PMID- 22359725
TI  - Glucose-6-Phosphate Dehydrogenase Deficiency among Male Blood Donors in Sana'a
      City, Yemen.
AB  - OBJECTIVES: To determine the prevalence of Glucose-6-phosphate dehydrogenase (G-6
      PD) deficiency among Yemeni people from different regions of the country living
      in the capital city, Sana'a, giving an indication of its overall prevalence in
      Yemen. METHODS: A cross-sectional study was conducted among Yemeni male blood
      donors attending the Department of Blood Bank at the National Centre of the
      Public Health Laboratories in the capital city, Sana'a, Yemen. Fluorescent spot
      method was used for screening, spectrophotometeric estimation of G-6-PD activity
      and separation by electrophoresis was done to determine the G-6-PD phenotype.
      RESULTS: Of the total 508 male blood donors recruited into the study, 36 were G-6
      PD deficient, giving a likely G-6-PD deficiency prevalence of 7.1%. None of these
      deficient donors had history of anemia or jaundice. Thirty-five of these
      deficient cases (97.2%) showed severe G-6-PD deficiency class II (<10% of normal
      activity), and their phenotyping presumptively revealed a G-6-PD-Mediterranean
      variant. CONCLUSION: The results showed a significant presence of G-6-PD
      deficiency with predominance of a severe G-6-PD deficiency type in these blood
      donors in Sana'a City, which could represent an important health problem through
      occurrence of hemolytic anemia under oxidative stress. A larger sample size is
      needed to determine the overall prevalence of G-6-PD deficiency, and should be
      extended to include DNA analysis to identify its variants in Yemen.

PMID- 22359727
TI  - Fetal amelia: a case report.
AB  - Congenital limb defects are rare fetal anomalies with a birth prevalence of 0.55
      per 1,000. Amelia is an extremely rare birth defect marked by the complete
      absence of one or more limbs. We report a case of fetal amelia, ultrasound
      findings, manifestations and the fetal outcome.

PMID- 22359726
TI  - Trends in waist circumference and central obesity in adults, northern iran.
AB  - OBJECTIVES: The main aim of this study is to determine the central obesity trends
      during the period from 2006 to 2010 among 15-65 years old people in Northern
      Iran. METHODS: This was a population-based cross-sectional study conducted on
      6466 subjects who had been chosen by a multi stage cluster random sampling within
      five steps. The subjects were randomly chosen from 325 clusters and each cluster
      included 20 cases. Central obesity was defined as waist circumference 3102 cm and
      388 cm in men and women, respectively. RESULTS: Compared to 2010, the mean waist
      circumference in 2006 changed from 87.2 cm to 88.1 cm in men (p=0.237), and from
      90.3 cm to 88.6 cm in women (p=0.045). The comparison between 2006 and 2010
      revealed that the prevalence of central obesity slightly decreased, 6.8% and 2.4%
      in urban women and men, respectively. Generally, the mean of waist circumference
      significantly decreased in urban women (by 0.069 cm in each year; p=0.020);
      however, the decrease of waist circumference in urban men was not significant
      (0.006 cm decrease each year; p=0.915). CONCLUSION: The prevalence of central
      obesity declined among both males and females in the urban area; however, there
      was an attenuated increasing trend in the rural area. The disparity of trends
      between the two regions should be considered for further study.

PMID- 22359728
TI  - Light chain deposition disease presenting as cholestatic jaundice: a case report.
AB  - Light-chain deposition disease (LCDD) is characterized by tissue deposition of
      the immunoglobulin light chains in multiple organs. These deposits appear similar
      to amyloid on routine sections, but differ in their staining properties and
      ultrastructural appearance. The deposits of LCCD are non -Congophilic and do not
      exhibit a fibrillar ultrastructure; while, the proteinaceous substance seen in
      primary amyloidosis is Congo red positive and fibrillar. One of the most common
      organs to be involved in LCDD is the kidney. Earlier reports on cases of LCDD
      have mostly shown simultaneous liver and renal involvement, there are very few
      cases in the literature describing LCDD of the liver without renal involvement.
      This report describes a patient who presented with severe cholestatic jaundice
      and liver cell failure with normal renal function.

PMID- 22359729
TI  - A novel v- silicone vestibular stent: preventing vestibular stenosis and
      preserving nasal valves.
AB  - This report presents a novel style of placing nasal stents. Patients undergoing
      surgical procedures in the region of nasal vestibule and nasal valves are at risk
      of developing vestibular stenosis and lifelong problems with the external and
      internal nasal valves; sequels of the repair. The objective of the report is to
      demonstrate a simple and successful method of an inverted V- Stent placement to
      prevent potential complication of vestibular stenosis and nasal valve compromise
      later in life. Following a fall on a sharp edge of a metallic bed, a sixteen
      month old child with a deep lacerated nasal wound extending from the collumellar
      base toward the tip of the nose underwent surgical exploration and repair of the
      nasal vestibule and nasal cavity. A soft silicone stent fashioned as inverted V
      was placed bilaterally. The child made a remarkable recovery with no evidence of
      vestibular stenosis or nasal valve abnormalities. In patients with nasal trauma
      involving the nasal vestibule and internal and external nasal valves stent
      placement avoids sequels, adhesions, contractures, synechia vestibular stenosis
      and fibrosis involving these anatomical structures. The advantages of the
      described V- stents over the traditional readymade ridged nasal stents, tubing's
      and composite aural grafts are: a) technical simplicity of use, b) safety, c)
      less morbidity, d) more comfortable, and e) economical. To our knowledge, this is
      the first report of such a stent for prevention of vestibular stenosis and
      preserving nasal valves.

PMID- 22359730
TI  - The Use of Total Cervical Occlusion along with McDonald Cerclage in Patients with
      Recurrent Miscarriage or Preterm Deliveries.
AB  - OBJECTIVES: To study the fetal outcome with the use of McDonald cerclage and
      total cervical occlusion in women with recurrent mid-trimester miscarriages or
      preterm deliveries, as well as complications of total cervical occlusion in the
      women. METHODS: Prospective descriptive observational study on patients with two
      or more mid-trimester miscarriages, deliveries before 36 weeks, or patients who
      have experienced failure of transvaginal cerclage. RESULTS: Twenty-six women were
      studied. Of these, 92% delivered at term. Two women delivered at 33 and 35 weeks,
      respectively. There was one neonatal death. Take home baby rate was 96.2%. There
      was no serious maternal morbidity among the patients. CONCLUSION: The addition of
      external cervical OS occlusion to McDonald cerclage could improve fetal outcome
      in women with recurrent mid-trimester miscarriages and preterm deliveries.

PMID- 22359731
TI  - Under representation of women in surgery in Nigeria: by choice or by design?
AB  - BACKGROUND: Female Doctors' lack of interest in surgical careers has raised much
      concern in recent times. An understanding of the factors responsible for this
      lack of interest and evolving attitude is needed. The aim of this report was to
      determine the local factors that may be responsible and the most likely surgical
      specialty female doctors would prefer. METHODS: This is a cross sectional study
      involving all female (consultant and resident) doctors in one teaching hospital.
      Information was obtained using a structured questionnaire which determined what
      formed the respondent's choice of present specialty. It also included the likely
      local factors that might have some bearings on the interest of female doctors in
      surgery. Data obtained were analyzed using SPSS version 11.5. RESULTS: There were
      a total of 105 respondents. The age range was 26 - 63 years (mean: 26.88+2.19).
      The factors that were considered as deterrents to female doctor choice of
      surgical career were: a) the impact on their time for family and other social
      engagements 29 (27.6%); b) heavy work load 22 (21%); c) involvement of a lot of
      physical effort 18 (17.1%); d) lack of women in surgery 9 (8.6%); and e) lack of
      role models 4 (3.8%). Twenty three (21.9%) considered all the above factors. The
      subspecialty preferred by most female was plastic and reconstructive surgery,
      followed by Pediatric surgery. CONCLUSION: The rigorous requirements of the
      training and practice of surgery deterred female doctors' interest in choosing
      and sustaining a surgical career. To maintain surgery as a premier career choice,
      female doctors should find surgery to be professionally and personally rewarding.

PMID- 22359732
TI  - Sneaky pancreatic head mass.

PMID- 22359733
TI  - Evidence Based Surgery: How Difficult is the Implication in Routine Practice?
AB  - Surgery as a discipline has perhaps been slower than other specialties to embrace
      evidence based principles. Today, surgeons all over Asia are prepared to
      challenge the dogma of yesterday. Surgical science which rests on a strong
      foundation of laboratory and clinical research can now be broadened to include
      the armamentarium of evidence based practice to advance surgical knowledge. The
      sheer volume of easily accessed information creates a new challenge. This article
      discusses keeping up with new information and finding the best available answers
      to specific questions amidst all the other information.

PMID- 22359734
TI  - DNA replication fading as proliferating cells advance in their commitment to
      terminal differentiation.
AB  - Terminal differentiation is the process by which cycling cells stop proliferating
      to start new specific functions. It involves dramatic changes in chromatin
      organization as well as gene expression. In the present report we used cell flow
      cytometry and genome wide DNA combing to investigate DNA replication during
      murine erythroleukemia-induced terminal cell differentiation. The results
      obtained indicated that the rate of replication fork movement slows down and the
      inter-origin distance becomes shorter during the precommitment and commitment
      periods before cells stop proliferating and accumulate in G1. We propose this is
      a general feature caused by the progressive heterochromatinization that
      characterizes terminal cell differentiation.

PMID- 22359735
TI  - Cell-Sized confinement in microspheres accelerates the reaction of gene
      expression.
AB  - Cell-sized water-in-oil droplet covered by a lipid layer was used to understand
      how lipid membranes affect biochemical systems in living cells. Here, we report a
      remarkable acceleration of gene expression in a cell-sized water-in-oil droplet
      entrapping a cell-free translation system to synthesize GFP (green fluorescent
      protein). The production rate of GFP (V(GFP)) in each droplet remained almost
      constant at least for on the order of a day, which implies 0(th)-order reaction
      kinetics. Interestingly, V(GFP) was inversely proportional to radius of droplets
      (R) when R is under 50 MUm, and V(GFP) in droplets with R ~ 10 MUm was more than
      10 times higher than that in the bulk. The acceleration rates of GFP production
      in cell-sized droplets strongly depended on the lipid types. These results
      demonstrate that the membrane surface has the significant effect to facilitate
      protein production, especially when the scale of confinement is on the order of
      cell-size.

PMID- 22359736
TI  - Spatio-temporal dynamics of a fish spawning aggregation and its fishery in the
      Gulf of California.
AB  - We engaged in cooperative research with fishers and stakeholders to characterize
      the fine-scale, spatio-temporal characteristics of spawning behavior in an
      aggregating marine fish (Cynoscion othonopterus: Sciaenidae) and coincident
      activities of its commercial fishery in the Upper Gulf of California.
      Approximately 1.5-1.8 million fish are harvested annually from spawning
      aggregations of C. othonopterus during 21-25 days of fishing and within an area
      of 1,149 km(2) of a biosphere reserve. Spawning and fishing are synchronized on a
      semi-lunar cycle, with peaks in both occurring 5 to 2 days before the new and
      full moon, and fishing intensity and catch are highest at the spawning grounds
      within a no-take reserve. Results of this study demonstrate the benefits of
      combining GPS data loggers, fisheries data, biological surveys, and cooperative
      research with fishers to produce spatio-temporally explicit information relevant
      to the science and management of fish spawning aggregations and the spatial
      planning of marine reserves.

PMID- 22359737
TI  - The prevalence of atopic dermatitis, asthma, and allergic rhinitis and the
      comorbidity of allergic diseases in children.
AB  - OBJECTIVES: Childhood allergic diseases are a major concern because they lead to
      a heavy economic burden and poor quality of life. The purpose of this study was
      to investigate the prevalence of childhood atopic dermatitis, asthma, allergic
      rhinitis, and the comorbidity of allergic diseases in Seoul, Korea. METHODS: We
      conducted a cross-sectional survey between May and October 2010 to evaluate the
      prevalence of childhood allergic diseases, including atopic dermatitis, asthma,
      and allergic rhinitis, using a questionnaire from the International Study of
      Asthma and Allergies in Childhood group. Each questionnaire was completed by the
      parent or guardian of a child. RESULTS: In the 31,201 children studied, the
      prevalence of atopic dermatitis symptoms in the past 12 months was 19.3% in
      children 0 to 3 years of age, 19.7% in children 4 to 6 years of age, 16.7% in
      children 7 to 9 years of age, and 14.5% in children 10 to 13 years of age (p for
      trend < 0.001). The prevalence of asthma in these age groups was 16.5%, 9.8%,
      6.5%, and 5.4%, respectively (p for trend < 0.001). The prevalence of allergic
      rhinitis in these age groups was 28.5%, 38.0%, 38.5%, and 35.9%, respectively (p
      for trend = 0.043). The percentage of subjects with both atopic dermatitis and
      asthma, both asthma and allergic rhinitis, or both atopic dermatitis and allergic
      rhinitis was 2.5%, 4.7%, and 8.7%, respectively. The prevalence of comorbid
      allergic diseases decreased with age (p for trend < 0.001). CONCLUSIONS: Our
      study revealed that the prevalence of some allergic diseases, such as atopic
      dermatitis and asthma, was relatively high in very young children and that all of
      the principal allergic diseases in children often co-exist.

PMID- 22359739
TI  - Proteoglycans: complex diversity in structure and functions.

PMID- 22359738
TI  - In Memoriam of John T. Shepherd, MD, DSc.

PMID- 22359740
TI  - Fluorodeoxyglucose positron emission tomography in Richardson's syndrome and
      progressive supranuclear palsy-parkinsonism.
AB  - BACKGROUND: We hypothesized that postural instability and cognitive decline in
      patients with Richardson's syndrome could be a consequence of reduced thalamic
      and frontal metabolism. Severe Parkinsonian signs in patients with progressive
      supranuclear palsy-parkinsonism may be reflected by alterations in putaminal
      metabolism. METHODS: Eleven patients with Richardson's syndrome, 8 patients with
      progressive supranuclear palsy-parkinsonism, 12 with Parkinson's disease, and 10
      controls underwent clinical assessment and fluorodeoxyglucose positron emission
      tomography (PET). RESULTS: Richardson's syndrome patients showed pronounced
      thalamic hypometabolism, and patients with progressive supranuclear palsy
      parkinsonism pronounced putaminal hypometabolism, compared to all other
      investigated groups. The putamen/thalamus uptake ratio differentiated progressive
      supranuclear palsy-parkinsonism from Richardson's syndrome (area under the curve
      5 0.86) and from Parkinson's disease (area under the curve 5 0.80) with
      acceptable accuracy. Frontal hypometabolism was predominantly found in
      Richardson's syndrome patients. CONCLUSIONS: Richardson's syndrome, progressive
      supranuclear palsy-parkinsonism and Parkinson's disease showed different
      metabolic patterns in fluorodeoxyglucose PET.

PMID- 22359741
TI  - Innovative orientations.

PMID- 22359742
TI  - Retraction notice to "Nef from SIVmac239 decreases proliferation and migration of
      adenoid-cystic carcinoma cells and inhibits angiogenesis" [OO 47 (2011) 847-854].

PMID- 22359743
TI  - The theme of emotion.

PMID- 22359744
TI  - Slow growth. But healthcare spending still doubles inflation rate.

PMID- 22359745
TI  - Equalizing pay. Battle erupts over MedPAC's backing of cuts.

PMID- 22359746
TI  - Thomson Reuters 100 Top Hospitals: 15 Top Health Systems.

PMID- 22359747
TI  - Push for 'repeal and replace' continues.

PMID- 22359748
TI  - Decision day on docket for ACA challenges.

PMID- 22359749
TI  - Congressional inaction sets up automatic cuts.

PMID- 22359750
TI  - Taxing, challenging times for non-profits.

PMID- 22359751
TI  - A takeover skirmish and acquisition flourish.

PMID- 22359752
TI  - Struggling economy delivers hits to bottom line.

PMID- 22359753
TI  - Cheers, qualms over value-based purchasing.

PMID- 22359754
TI  - Year-long uncertainty over doc-pay fix.

PMID- 22359755
TI  - Feds offer some relief as ACA rollout continues.

PMID- 22359756
TI  - IT incentive money starts flowing to providers.

PMID- 22359757
TI  - Unsettling news on disaster preparedness.

PMID- 22359758
TI  - Nursing homes cope with deep payment cut.

PMID- 22359759
TI  - Most profitable critical-access hospitals. Ranked by net income from the CMS
      Hospital Cost Report released June 30.

PMID- 22359760
TI  - Firing blanks. CBO says experiments fail to cut Medicare spending; providers not
      ready to give up.
AB  - The results are in, and it's bad news for saving money in care coordination and
      disease management, according to the Congressional Budget Office, which found
      demonstration projects in those areas didn't save Medicare money. Randy Brown,
      left, of Mathematica Policy Research, says it's not surprising since it's hard to
      save money on a very sick population with chronic problems.

PMID- 22359761
TI  - Lifting Medicaid barriers. States work to upgrade IT to meet 2014 deadline.

PMID- 22359762
TI  - Some states reluctant. Little known on federal exchange plans.

PMID- 22359763
TI  - Duel over discounts. Pharma, providers at odds over 'orphan drugs'.

PMID- 22359764
TI  - Largest academic medical centers. Ranked by total number of residents and interns
      based on Medicare cost report information, 2010.

PMID- 22359765
TI  - Thorny patch. Short-term doc fix leaves long-term question.

PMID- 22359766
TI  - Essentially astute ... but experts say benefit flexibility may cause trouble.

PMID- 22359767
TI  - Most frequently billed Medicare DRGs. Ranked by 2010 Medicare patient discharges.

PMID- 22359768
TI  - Mending the pay patch. Effort looks to war savings for SGR replacement.

PMID- 22359769
TI  - Taking aim at ACA. GOP vows to rev up offense as Obama hints at easing defense of
      reform.

PMID- 22359770
TI  - Avoiding the penalty box. New rules on readmissions push hospitals, post-acute
      providers into closer collaboration.

PMID- 22359771
TI  - Largest healthcare services mergers/acquisitions in 2011. Completed or pending
      U.S. transactions ranked by the deal's price.

PMID- 22359772
TI  - CBO projects rise in spending. Cuts, changes needed to prevent 'substantial
      harm'.

PMID- 22359773
TI  - Health benefits feedback. Suggestions to HHS include flexibility, clarity.

PMID- 22359774
TI  - Largest professional liability carriers. Ranked by direct premiums written for
      medical professional liability in the U.S. in 2010.

PMID- 22359782
TI  - Bibliography of secondary sources on the history of dermatology: I. Journal
      articles in English supplemented through 2010.

PMID- 22359783
TI  - Bibliography of secondary sources on the history of dermatology: III. Books,
      monographs, and chapters in English supplemented through 2010.

PMID- 22359784
TI  - Clarifications regarding veterinary school accreditation.

PMID- 22359785
TI  - Ovariectomy during early pregnancy.

PMID- 22359786
TI  - Corrections regarding hyperkalemia pathophysiology.

PMID- 22359787
TI  - Question about fish oil dosages.

PMID- 22359788
TI  - Use of dexmedetomidine and ketamine in combination with opioids.

PMID- 22359789
TI  - Veterinary school class size and job outlook.

PMID- 22359790
TI  - Use of dexmedetomidine and ketamine in combination with opioids.

PMID- 22359791
TI  - Administrative simplification: adoption of standards for health care electronic
      funds transfers (EFTs) and remittance advice. Interim final rule with comment
      period.
AB  - This interim final rule with comment period implements parts of section 1104 of
      the Affordable Care Act which requires the adoption of a standard for electronic
      funds transfers (EFT). It defines EFT and explains how the adopted standards
      support and facilitate health care EFT transmissions.

PMID- 22359792
TI  - Vocational rehabilitation and employment program--changes to subsistence
      allowance. Final rule.
AB  - This document adopts as final, without change, the interim final rule amending
      regulations of the Department of Veterans Affairs (VA) to reflect changes made by
      the Post-9/11 Veterans Educational Assistance Improvements Act of 2010, effective
      August 1, 2011, that affect payment of vocational rehabilitation benefits for
      certain service-disabled veterans. Pursuant to these changes, a veteran, who is
      eligible for a subsistence allowance under chapter 31 of title 38, United States
      Code, and educational assistance under chapter 33 of title 38, United States
      Code, may participate in a rehabilitation program under chapter 31 and elect to
      receive a payment equal in amount to an applicable military housing allowance
      payable under title 37, United States Code, instead of the regular subsistence
      allowance under chapter 31. In addition, payments of subsistence allowances
      during periods between school terms are discontinued, and payments during periods
      of temporary school closings are modified.

PMID- 22359793
TI  - Medicare program; Medicare Advantage and prescription drug benefit programs:
      negotiated pricing and remaining revisions; prescription drug benefit program:
      payments to sponsors of retiree prescription drug plans. Final rule.
AB  - This final rule implements and finalizes provisions regarding the reporting of
      gross covered retiree plan-related prescription drug costs (gross retiree costs)
      and retained rebates by Retiree Drug Subsidy (RDS) sponsors; and the scope of our
      waiver authority under the Social Security Act (the Act).

PMID- 22359794
TI  - Amendments to regulations regarding eligibility for a Medicare prescription drug
      subsidy. Final rule.
AB  - This final rule adopts, without change, the interim final rule with request for
      comments we published in the Federal Register on December 29, 2010. The interim
      final rule incorporated changes to the Medicare prescription drug coverage low
      income subsidy (Extra Help) program made by the Patient Protection and Affordable
      Care Act (Affordable Care Act) enacted in March 2010. Under our interpretation of
      section 3304 of the Affordable Care Act, if the death of a beneficiary's spouse
      would decrease or eliminate the subsidy provided by the Extra Help program, we
      will extend the effective period of eligibility for the most recent determination
      or redetermination until one year after the month following the month we are
      notified of the death of the spouse. The effective date of this provision was
      January 1, 2011. We also revised our regulations to incorporate changes made by
      the Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) which
      affect the way we account for income and resources when determining eligibility
      for the Extra Help program. The statute provides that we no longer count the
      value of any life insurance policy as a resource for Extra Help effective on and
      after January 1, 2010. As of that date, we also no longer count as income the
      help a beneficiary receives when someone else provides food and shelter, or pays
      household bills for food, mortgage, rent, electricity, water, property taxes, or
      heating fuel or gas. These revisions updated our rules to reflect these statutory
      changes.

PMID- 22359795
TI  - A depiction of male same-sex seduction in Ambrogio Lorenzetti's "Effects of Bad
      Government" fresco.

PMID- 22359796
TI  - Nutrition standards in the National School Lunch and School Breakfast Programs.
      Final rule.
AB  - This final rule updates the meal patterns and nutrition standards for the
      National School Lunch and School Breakfast Programs to align them with the
      Dietary Guidelines for Americans. This rule requires most schools to increase the
      availability of fruits, vegetables, whole grains, and fat-free and low-fat fluid
      milk in school meals; reduce the levels of sodium, saturated fat and trans fat in
      meals; and meet the nutrition needs of school children within their calorie
      requirements. These improvements to the school meal programs, largely based on
      recommendations made by the Institute of Medicine of the National Academies, are
      expected to enhance the diet and health of school children, and help mitigate the
      childhood obesity trend.

PMID- 22359797
TI  - The virtues of childhood sexual abuse and marital infidelity in Marie-Jeanne
      Roland's "Memoires particuliers"(1795).

PMID- 22359798
TI  - Sexual Assault Prevention and Response (SAPR) Program. Interim final rule.
AB  - This part implements Department of Defense (DoD) policy and assigns
      responsibilities for the SAPR Program on prevention, response, and oversight to
      sexual assault. It is DoD policy to establish a culture free of sexual assault by
      providing an environment of prevention, education and training, response
      capability, victim support, reporting procedures, and accountability that
      enhances the safety and well being of all persons covered by the regulation.

PMID- 22359799
TI  - Replotting the ethnographic romance: revolutionary Frenchmen in the Pacific, 1768
      1804.

PMID- 22359800
TI  - Dental conditions. Final rule.
AB  - The Department of Veterans Affairs (VA) adopts as a final rule the proposal to
      amend its adjudication regulations regarding service connection of dental
      conditions for treatment purposes. This amendment clarifies that principles
      governing determinations by VA's Veterans Benefits Administration (VBA) for
      service connection of dental conditions for the purpose of establishing
      eligibility for dental treatment by VA's Veterans Health Administration (VHA),
      apply only when VHA requests information or a rating from VBA for those purposes.
      This amendment also clarifies existing regulatory provisions and reflects the
      respective responsibilities of VHA and VBA in determinations concerning
      eligibility for dental treatment.

PMID- 22359801
TI  - Where else but Greenwich Village? Love, lust, and the emergence of the American
      Civil Liberties Union's sexual rights agenda, 1920-1931.

PMID- 22359802
TI  - Further amendments to general regulations of the Food and Drug Administration to
      incorporate tobacco products. Final rule.
AB  - The Food and Drug Administration (FDA) is amending certain of its general
      regulations to include tobacco products, where appropriate, in light of FDA's
      authority to regulate these products under the Family Smoking Prevention and
      Tobacco Control Act (Tobacco Control Act). With these amendments, tobacco
      products are subject to the same general requirements that apply to other FDA
      regulated products.

PMID- 22359803
TI  - Sex and the ordinary Cuban: Cuban physicians, eugenics, and marital sexuality,
      1933-1958.

PMID- 22359804
TI  - Exceptions or alternatives to labeling requirements for products held by the
      Strategic National Stockpile. Final rule.
AB  - The Food and Drug Administration (FDA) is adopting as a final rule, without
      change, the interim final rule that issued regulations permitting FDA Center
      Directors to grant exceptions or alternatives to certain regulatory labeling
      requirements applicable to human drugs, biological products, or medical devices
      that are or will be included in the Strategic National Stockpile (SNS). FDA is
      taking this action to complete the rulemaking initiated with the interim final
      rule.

PMID- 22359805
TI  - Guidelines for determining probability of causation under the Energy Employees
      Occupational Illness Compensation Program Act of 2000; revision of guidelines on
      non-radiogenic cancers. Final rule.
AB  - In a notice of proposed rulemaking published in the Federal Register on March 21,
      2011, the Department of Health and Human Services (HHS) proposed to treat chronic
      lymphocytic leukemia (CLL) as a radiogenic cancer under the Energy Employees
      Occupational Illness Compensation Program Act of 2000 (EEOICPA) (76 FR 15268).
      Under this final rule, CLL will be treated as being potentially caused by
      radiation and hence as potentially compensable under EEOICPA. HHS reverses its
      decision to exclude CLL from such treatment.

PMID- 22359806
TI  - Schedule for rating disabilities; AL amyloidosis (primary amyloidosis). Final
      rule.
AB  - The Department of Veterans Affairs (VA) is amending its Schedule for Rating
      Disabilities by updating the schedule of ratings for the hemic and lymphatic
      systems to include AL amyloidosis. This regulatory action is necessary to add AL
      amyloidosis as one of the disease conditions and establish criteria for
      disability evaluation to fully implement the decision by the Secretary of
      Veterans Affairs to grant presumptive service connection based on herbicide
      exposure for this disease. The intended effects are to provide consistency in
      disability ratings and to ease tracking of AL amyloidosis for statistical
      analysis.

PMID- 22359808
TI  - Veterinarians pivotal in responsible animal ownership.

PMID- 22359807
TI  - The importance of veterinary behavioural medicine in veterinary practice.

PMID- 22359809
TI  - Changes in the workplace for 2012.

PMID- 22359812
TI  - Important areas to be addressed.

PMID- 22359814
TI  - New American Association of Colleges of Nursing data show significant enrollment
      increases in baccalaureate, master's, and doctoral nursing degree programs.

PMID- 22359815
TI  - [Memoirs of the late Prof. Tamotsu Takimoto].

PMID- 22359816
TI  - [Memoirs of the late Prof. Vinci Mizuhira].

PMID- 22359817
TI  - [Memoirs of the late Prof. Ryosuke Miyauchi].

PMID- 22359818
TI  - Clinical techniques of performing suctioning tasks and of positioning the high
      volume evacuation (HVE) attachment and inlet when assisting a dentist. A guide
      for dental assistants: part 2.
AB  - When assisting a dentist, an assistant may need to hold the high volume
      evacuation (HVE) attachment and use it to suction aerosols produced by the
      dentist's tools, particularly the high speed handpiece or the cavitron. The main
      objective of suctioning is to hold the inlet of the HVE attachment close enough
      to the source of aerosols to evacuate those aerosols, while avoiding suctioning
      of the patient's intra-oral soft tissues, and avoiding contact of the HVE
      attachment with the handpiece, cavitron or other instrument that the dentist is
      using. In general, assisting a dentist with suctioning is a somewhat complex
      skill that may require months of experience before an assistant develops an
      intuition for suctioning. This is the second part of a two-part article, and
      focuses on how to position the HVE suction inlet at various locations intra
      orally and on how to maintain and clean the dental office suction pipes.

PMID- 22359819
TI  - Limit the spread of contamination.

PMID- 22359820
TI  - Integrity, service and excellence: the experiences of USAF dental assistant
      instructors.

PMID- 22359821
TI  - Nursing across borders.

PMID- 22359822
TI  - The Institute of Medicine Report: The Future of Nursing: what it means to the
      APRN.

PMID- 22359823
TI  - Millennial nurses in the workplace.

PMID- 22359824
TI  - Committing to a new approach to policymaking.

PMID- 22359825
TI  - In my backyard.

PMID- 22359826
TI  - Influence your practice: pray!

PMID- 22359827
TI  - Hope yields health: offering whole person care.

PMID- 22359828
TI  - Historically informed nursing.

PMID- 22359829
TI  - Caring for familiar strangers.

PMID- 22359830
TI  - Motivational interviewing: helping patients move toward change.
AB  - Motivational Interviewing (MI) is a valuable tool for nurses to help patients
      address behavior change. MI has been found effective for helping patients with
      multiple chronic conditions, adherence issues, and lifestyle issues change their
      health behaviors. For Christian nurses, MI is consistent with biblical principles
      and can be seen as a form of ministry. This article overviews the process of MI,
      stages of change, and offers direction for further learning.

PMID- 22359831
TI  - When tragedy is our own.
AB  - How do members of a nursing uint and a healthcare center find their way through
      the tragic loss of a friend and colleague? This article shares how the hospital
      "family" came together to offer support and empathy to one another, and how God
      revealed himself amidst the loss.

PMID- 22359832
TI  - Helping human trafficking victims in our backyard.
AB  - Human trafficking is the fastest growing criminal enterprise in the world.
      Healthcare professionals are uniquely positioned to discover individuals who are
      trafficked and intervene. This article describes the problem, discusses red flags
      to watch for, common ailments in victims, screening questions if trafficking is
      suspected, and proactive steps to take in your workplace to deal with human
      trafficking.

PMID- 22359833
TI  - Knitting an amazing nurse.
AB  - How are faith and spirituality integrated into nursing? This article explores how
      personal faith can be either imbricated or isolated with nursing practice and
      education.

PMID- 22359834
TI  - No time to fear: new nurse assists patients following Joplin tornado. Interview
      by Sandy Painter.
AB  - A new nurse is interviewed after working with patients following the May 22, 2011
      Joplin, Missouri, Tornado.

PMID- 22359835
TI  - Hospital outreach to support faith community nursing.
AB  - A Faith Community Nurse (FCN) Program was initiated by a Magnet hospital and
      developed through collaboration between hospital departments and a university
      nurse educator. This article describes the program's development and activities
      that offer FCNs networking, free continuing education, and are an extension of
      the hospital's mission and values.

PMID- 22359836
TI  - Faith-based cognitive behavioral therapy: easing depression in the elderly with
      cognitive decline.
AB  - Minimizing depression in residential aged care facilities is a formidable
      challenge but doing so may improve quality of life and protect against dementia.
      A pilot project with residents with cognitive decline and concurrent depression
      tested the suitability of a faith-based cognitive behavioral therapy (CBT)
      intervention in reducing participant levels of depression, offering promising
      results.

PMID- 22359837
TI  - Recipe for health: impacting diabetes in African Americans through faith-based
      edcuation.
AB  - The Recipe For Health educational initiative was designed to increase knowledge
      of diabetes prevention and management for African Americans (AAs) in rural
      Alabama. By providing culturally competent information, training, and skill
      building activities to lay leaders in faith-based settings who teach church
      members, Recipe For Health can create a ripple effect of diabetes knowledge that
      could lower disease complications in the AA population.

PMID- 22359838
TI  - God's dominion over death.
AB  - This article briefly overviews the criteria for and physiological process of
      death, contrasting physical death with biblical passages revealing how God
      interceded in this universal process when Jesus was on earth.

PMID- 22359839
TI  - How do I care for those who are isolated?

PMID- 22359840
TI  - What do you want me to do for you?

PMID- 22359841
TI  - Preparing for nursing ministry.

PMID- 22359842
TI  - Neurosyphilis and organic psychosis.
AB  - Neurosyphilis is a Central Nervous System infection that can manifest as a
      psychiatric condition. Although neurosyphilis is not widely considered in the
      differential when patients present with psychiatric symptoms, routine Rapid
      Plasma Reagin (RPR) screening is indicated when assessing new-onset psychiatric
      illness. This case report will illustrate the usefulness of RPR testing for
      patients admitted to inpatient or outpatient psychiatric treatment.

PMID- 22359843
TI  - Practical nurses' health and safety in nursing homes.
AB  - PURPOSE: Practical nurses (PNs) rated their general and emotional health and
      their employers' attention to their health and safety. These components were
      examined in relationship to work setting and intention to leave for the purpose
      of exploring workforce issues involving these important care providers of frail
      elders. DESIGN/METHODS: A relicensure survey mailed to all PNs in one rural state
      included the Minimum Data Set for nurse workforce supply plus questions from the
      Health and Retirement Survey. Data were analyzed using Kruskal-Wallis
      nonparametric ANOVA, t-test, and chi-square tests. RESULTS: Of the state's
      working PNs, 813 responded, (71%) and 34% (n=269) reported nursing home
      employment. Overall, age and work role were not significantly associated with
      self-rated general health (p=0.14 and p=0.12). Males reported poorer general
      (p=0.09) and emotional (p=0.004) health. PNs working in nursing homes rated their
      general and emotional health lower than PNs in other settings (p<0.001). Of the
      PNs in nursing homes, 28% reported they were likely to leave their position
      within one year, versus 19% in other work settings (p=0.003). PNs with higher
      evaluations of their employer safety practices were less likely to leave.
      IMPLICATIONS: Understanding PNs perceived general/emotional health and
      perceptions of workplace health/safety efforts can inform interventions to reduce
      turnover.

PMID- 22359845
TI  - Asthma education information source preferences and their relationship to asthma
      knowledge.
AB  - This study recounts the findings from a year-long survey of Brooklyn residents.
      Survey respondents were questioned about their knowledge of asthma signs,
      triggers, symptoms and their attitudes and beliefs about asthma. If they had
      asthma or were responsible for a child or adult who had asthma they were asked
      questions to determine how well that asthma was controlled. They were also
      questioned about their preferred sources of asthma information. Descriptive and
      inferential statistics indicate that the survey respondents (mostly African
      American, middle aged, females) were generally knowledgeable about asthma,
      although they shared some misconceptions about asthma treatments and triggers.
      They showed a marked preference for obtaining their asthma information from
      traditional Western medicine providers rather than friends, family members,
      alternative or complimentary medicine providers or spiritual leaders. This
      information is useful in guiding investments of time and resources for asthma
      education programs addressing such audiences. It is also useful for planning
      health care education programs for a variety of disorders, including high blood
      pressure and diabetes.

PMID- 22359844
TI  - Health disparity: time delay in the treatment of breast cancer in Louisiana.
AB  - Previous studies have suggested that breast cancer patients with a delay of three
      months or more in initiating radiotherapy after breast conservative surgery, have
      increased recurrence and lower survival than those without treatment delay. In
      this study, the inequalities in receiving radiation on time after surgery were
      identified in five areas--patient's age at diagnosis, race, size of the facility
      where the patient received treatment, teaching status of the facilities and
      geographical location where the patient received treatment. All patients studied
      were female patients. Women younger than 50 years of age, of the black race,
      receiving treatment in a teaching hospital, and who were treated by surgeons in
      southeast and central Louisiana were more likely to experience delay in receiving
      radiotherapy after breast conservative surgery than their counterparts. Patient's
      insurance status, marital status and SES did not have any influence on treatment
      delay. Also, the surgeon's practice age at diagnosis, the surgeon's medical
      school, facility ownership status and Commission on Cancer approval status did
      not show significant effect.

PMID- 22359846
TI  - Evaluation of cross-disciplinary training on the co-occurrence of domestic
      violence and child victimization: overcoming barriers to collaboration.
AB  - The co-occurrence of child abuse and domestic violence has gained increasing
      attention over the last several years. As a result, there have been a number of
      efforts around the country to cross-train domestic violence and child welfare
      workers. Many of these initiatives are based on recommendations derived from
      prior research which emphasizes the importance of cross training child welfare
      workers, domestic violence advocates, and others in order to enhance interagency
      collaborations and ultimately improve the handling of co-occurrence cases. Using
      a survey design and two samples of child protective service (CPS) workers were
      drawn, this paper evaluates the effectiveness of a statewide initiative to
      improve inter-agency collaboration through a series of cross-disciplinary
      trainings. Special attention is also given to the identification of barriers and
      their potential role in shaping collaboration. While this study did not find
      significant changes in CPS workers' knowledge, attitudes, or self-reported levels
      of collaboration overall as a result of the training, collaboration was found to
      be related to increased knowledge and positive attitudes toward collaboration
      post training. The findings further demonstrate that efforts to cross-train staff
      can change the way CPS workers view the presence of some barriers to
      collaboration. Implications for future research and strategies for enhancing
      inter-agency collaboration in co-occurrence cases are discussed.

PMID- 22359847
TI  - HIPAA and what it means to you.

PMID- 22359848
TI  - Older inpatients stranded by cuts.

PMID- 22359849
TI  - "It's your responsibility to report patient safety concerns".

PMID- 22359850
TI  - Words strong but action vague in PM plan.

PMID- 22359851
TI  - "Skateboards will be needed to deliver hourly ward rounds".

PMID- 22359852
TI  - 'Focus on the values of nursing to boost care--not checklists".

PMID- 22359853
TI  - Engaging staff with intentional rounding.
AB  - This article describes the introduction of intentional rounding on a busy medical
      assessment unit and how staff engagement and understanding of the process is
      essential to its successful rollout. Staff's reaction to the implementation is
      highlighted and the benefits to care delivery discussed.

PMID- 22359854
TI  - Do ward sisters have influence over care?
AB  - The role of the ward sister has changed significantly since modern nursing began
      in the 19th century. This article looks at the history of the ward sister,
      explores the impact of political and professional changes on the role and
      discusses how ward sisters can help maintain the quality of care in today's NHS.

PMID- 22359855
TI  - Preparing injectable medicines safely.
AB  - Risks to patients are greater when injectable medicines are prepared in clinical
      areas (wards, theatres, clinics or even patients' homes), rather than provided in
      ready-to-use form. This article describes the risks involved in preparing
      injectable medicines in such areas and outlines key principles to ensure they are
      prepared safely. It also suggests that high-risk injectable medicines be provided
      in ready-to-use form, either in house, by pharmacy or by pharmaceutical
      companies.

PMID- 22359856
TI  - Moving on up.

PMID- 22359858
TI  - A decade of change, a century of need.

PMID- 22359857
TI  - Stick to your New Year's resolutions.

PMID- 22359859
TI  - Laryngeal transplant. The University of California Davis nursing experience.

PMID- 22359860
TI  - A need for health care reform. Cancer care costs and the patient perspective.

PMID- 22359861
TI  - [Influence of natural complex compounds with hipolipidemic activity on expression
      of bacteria virulence factors].
AB  - Natural complex compounds with hipolipidemic activity, having considerable
      inhibitory effect on expression of bacteria virulence factors were isolated.
      Inhibitory properties of the compounds with respect to pyocyanine and protease
      formation, as well as their influence on the quorum sensing mechanism in
      Chromobacterium violacium were shown.

PMID- 22359862
TI  - [Investigation of ampicillin effect on morphological and mechanical properties of
      Escherichia coli and Bacillus cereus cells with atomic force microscopy].
AB  - The effect of subbacteriostatic concentrations of ampicillin on morphological and
      mechanical properties of gramnegative and grampositive cells of Escherichia coli
      K12 TG1 and Bacillus cereus IP 5832 respectively was studied with atomic force
      microscopy. Significant heterogeneity of the bacterial populations was shown by
      the character of the response to the antibiotic effect. The common feature was
      increase of the cell size likely due to the effect of the inner osmotic pressure
      on the lowered cell wall strength. In the E. coli population there were besides
      observed anomalous elongated cells with signs of septation disorder, as well as
      their structurs, lacking the cytoplasmic liquid fraction. In the B. cereus the
      inner osmotic pressure mainly enlarged the cell cross section, changing the cell
      shape from rod to sphere, that was accompanied by significant impairment of the
      surface structure with liberation of the peptidoglycane fragments to the medium.
      The particular features of the E. coli K12 TG1 and B. cereus IP 5832 respond to
      the ampicillin effect were attributed to the differences in the structure of
      their cell wall, also due to specific properties of the peptidoglycane synthesis
      and three-dimensional organization.

PMID- 22359863
TI  - [Investigation of luromarin efficacy on mice with experimental tick-borne
      encephalitis].
AB  - Oral use of Luromarin, extracted from sea algae Zostera asiatica, was efficient
      in protection of mice from lethal infection induced by highly pathogenic strain
      of TBE virus, by extending their average lifespan. Luromarin demonstrated
      potentiating action in combination with ribavirin and cycloferon.

PMID- 22359864
TI  - [In vitro induction of transmissive resistance to tetracycline, chloramphenicol
      and ampicillin chloramphenicol in Vibrio cholera non-O1/non-O139 serogroups
      isolated within 1990-2005].
AB  - Inducible character of resistance to tetracycline, chloramphenicol and ampicillin
      was investigated in 20 strains of Vibrio cholera non-O1/non-O139 serogroups
      isolated from inhabitants of Uzbekistan in 1990 (10 strains, ctx+) and in 2001 (5
      strains, ctx-) and from inhabitants of Kalmykiya within 2003-2005 (5 strains, ctx
      ). Eight of the 20 isolates showed not only capacity for induction of the
      antibiotic resistance, but also its possible self transfer to Escherichia coli
      and reverse crosses in El Tor V. cholerae P-5879. It was shown that the effect of
      the antibacterial on the isolates phenotypic susceptibility could increase the
      resistance markers expression, when the genomes contained sites responsible for
      their expression, that required constant bacteriological control of the treatment
      efficacy and the use of the isolates antibioticograms for early replace of the
      inefficient drug by the efficient one. The prevalence of V. cholerae O1 and non
      O1/non-O13 serogroups with multiple resistance to the antibacterial and the
      genetic potency for the antibiotic resistance development in the pathogen made
      difficult the choice of efficient drugs for prophylaxis and treatment of diseases
      caused by V. cholerae.

PMID- 22359865
TI  - [Efficacy and tolerance of rezonizate in complex with fluoroquinolones or
      mycobutin on a model of experimental murine tuberculosis].
AB  - The efficacy of rezonizate, a novel antituberculosis drug, in combination with
      fluoroquinolones or mycobutin was studied in experiments on mice infected with
      Mycobacterium tuberculosis. By the pathomorphological and microbiological
      criteria, the highest therapeutic effect was observed when rezonizate was used in
      combination with levofloxacin, the lowest effect was produced by rezonizate
      combination with gatifloxacin.

PMID- 22359866
TI  - [Antiulcerous efficacy of reamberin at the background of the stress ulcerogenic
      factor action].
AB  - The effect of reamberin on morphofunctional changes in the small intestine mucous
      membrane due to stress ulcerogenesis was studied. Normalization of the lipid
      modifications in the tissue structure, evident of the drug antiulcerous
      properties, was observed.

PMID- 22359867
TI  - [Rapid determination of ceftriaxone in mixed saliva of practically healthy
      subjects and patients with infectious and somatic pathologies].
AB  - A method for spectroscopic determination of ceftriaxone in saliva of healthy
      subjects and patients with upper respiratory tract infections was developed. The
      concentration range is 1-50 mcg/ml. The method is express and simple, and can be
      used to determine ceftriaxone in clinical tests and pharmacokinetic studies.
      Possible determination of ceftriaxone in aqueous solutions was demonstrated which
      is useful in analysis of drugs.

PMID- 22359868
TI  - [Improvement of herpetic stomatitis therapy in patients with chronic
      tonsillitis].
AB  - To determine the clinicopathogenetic efficacy of cycloferon liniment in combined
      therapy of herpetic stomatitis, 60 patients with herpetic stomatitis and chronic
      tonsillitis were examined and treated. It was shown that the use of cycloferon
      liniment in the combined therapy of herpetic stomatitis in the patients with
      chronic tonsillitis allowed to lower the infection load in the parodontal
      recesses and the local inflammation, to normalize the immunity indices and to
      reduce the level of the endogenous intoxication, that provided acceleration of
      the recuperation processes and decreased the frequency of stomatitis backsets.

PMID- 22359869
TI  - [Combined management of colon cancer local recurrences with using intraabdominal
      chemotherapy].
AB  - The efficacy of intraabdominal chemotherapy in management of local recurrences of
      colon cancer was studied. Intraabdominal intraoperative and early postoperative
      chemotherapy made it possible to prolong of the recurrenceless term and to
      improve the life quality of the patients with local recurrences of colon cancer.
      There was observed a tendency to increase the five-year survival.

PMID- 22359870
TI  - [Experience with empirical treatment of severe acute respiratory syndrome due to
      coronavirus, genotype IV].
AB  - Foreign experience with empirical management of severe acute respiratory syndrome
      (SARS) due to coronavirus, genotype IV is described. It is indicated that the
      data on the efficacy of ribavirin with respect to SARS in the patients are
      contradictory. The efficacy of two chemotherapeutics, i. e. lopinavir and
      ritonavir used in the SARS foci is confirmed. The drugs are at present applicable
      all over the world in retrovirus therapy of HIV infected subjects. The search for
      efficient Russian unspecific medicines for control of SARS is actual.

PMID- 22359871
TI  - [Ceftaroline fosamil, a broad spectrum cephalosporin antibiotic for the treatment
      of community-acquired pneumonia and complicated skin and skin structure
      infections].

PMID- 22359872
TI  - [Chronologic annotation on the development of allergology and clinical immunology
      in Croatia].
AB  - This issue of Acta Medica Croatica is dedicated to historical development and
      role of allergology and clinical immunology in Croatia. Also listed are the names
      of experts who have historically marked allergology and contributed to its
      development. Understanding the origin of allergies as immune phenomena occurred
      in Croatia simultaneously to many other European countries. The origin and
      development of institutions established in the early 1920s constituted the
      backbone of a solid vertical line, crucial for the development of allergology and
      immunology in Croatia during the past century. Interest of allergology experts
      from various medical specialties has resulted in the establishment of Allergy
      Section at the Croatian Medical Association in 1952, now Croatian Society of
      Allergology and Clinical Immunology of the Croatian Medical Association. It
      turned out that the work of institutions and physicians, as well as cooperation
      with the Croatian Immunological Society and other scientific institutions during
      the second half of the 20th century provided solid foundation for contemporary
      research, design and development of allergy subspecialty centers and units at
      various medical institutions all over Croatia. Members of the Croatian Society of
      Allergology and Clinical Immunology have played an important role in educating
      new generations of physicians and in the organization of numerous research
      projects, symposia, congresses and seminars. Continuous, scientific and
      professional work has resulted in active Society membership in the European
      Academy of Clinical Immunology and Allergology.

PMID- 22359873
TI  - [Atopic dermatitis in children and adults].
AB  - Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease
      characterized by itching and typical clinical features, depending on patient age.
      It is often associated with other atopic diseases such as asthma or allergic
      rhinitis, resulting from the complex etiology and pathogenesis. It occurs more
      frequently in people with genetic predisposition for atopic diseases. The
      intensity and extent of skin lesions (Scoring of Atopic Dermatitis, SCORAD Index)
      vary significantly among AD patients, depending on whether it is acute or
      chronic, and there are variations in laboratory parameters, especially immune. In
      the future, it will be necessary to reach consensus on the new criteria for
      defining AD instead of the old ones (brought by Hanifin and Rajka 31 years ago).
      What is needed is effective and safe treatment, and control of the early stages
      of AD as well as maintaining AD remission. The new therapeutic approach in AD has
      greatly improved the quality of life of AD patients. As the prevalence of the
      disease continues to increase, we emphasize the importance of prevention, prompt
      recognition and optimal treatment of the many patients with AD.

PMID- 22359874
TI  - [Atopy patch test--when is it useful?].
AB  - The aim of the article is to introduce the atopy patch test (APT) as a model of
      cellular immunity reaction. APT is epicutaneous test performed with food and
      aeroallergens, and represents a good model for T lymphocyte hypersensitivity. It
      is compared with skin prick test (SPT). Its value is supported by the fact that
      atopic dermatitis is the result of complex immune interactions and involves both
      Coombs and Gell reactions type IV and I. In this review, we shortly discuss the
      etiopathogenesis of atopic dermatitis, distinction of extrinsic and intrinsic
      issues, and compare the value of APT with SPT and IgE determination. APT includes
      epicutaneous application of type I allergens known to elicit IgE mediated
      reactions, followed by evaluation of eczematous skin reaction after 48 and 72
      hours. The limitations of ATP include the lack of test standardization, but there
      also are comparative advantages over SPT and specific IgE determination. We also
      briefly discuss the most important food and aeroallergens. APT has been
      recognized as a diagnostic tool in the evaluation of food allergy and
      aeroallergens such as house dust mite, pollen and animal dander. APT is a useful
      diagnostic procedure in patients with atopic dermatitis allergic to inhalant
      allergens and in children with food allergy younger than 2 years. The sensitivity
      and specificity of the test greatly depend on the allergen tested and patient
      age.

PMID- 22359875
TI  - [Photoallergic drug reactions].
AB  - Drug-induced hypersensitivity reactions include phototoxic and photoallergic
      reactions. Photoallergic reactions, which develop as cell-mediated immune
      responses to a light-activated compound, are described in this review article.
      The main topics include photobiology, list of common drugs inducing photoallergic
      reactions, immune response, clinical features, diagnostic and therapeutic
      approach. Photoallergic drug reactions can be avoided in most cases if the
      potential photoallergens are known and appropriate photoprotection is used.

PMID- 22359876
TI  - [Allergologic emergencies in dermatology--diagnostic and therapeutic procedures].
AB  - Emergencies in allergology and clinical immunology are quite common and pose a
      public health problem in Croatia and worldwide. Allergic reactions ranging from
      mild symptoms such as pruritus to generalized skin eruptions, gastrointestinal
      and respiratory symptoms to anaphylaxis with cardiovascular emergencies are very
      common. Reaction develops to inhalant substances, food and food ingredients,
      various foreign substances (blood, latex, etc.) and many other well known
      antigens and drugs which are frequent causes of anaphylactic reactions, asthma,
      generalized urticaria, angioedema. There are 35 different skin reactions induced
      by drugs through immune complexes, complement mediated reactions and direct
      histamine liberation (by opiates or dextran) and modulators of arachidonic acid
      metabolism (such as NSAID). Along with painful infiltrates, insect venom allergy
      manifests with disseminated exanthema and angioedema. Current diagnostic methods,
      especially therapeutic procedures for emergencies in concordance with the
      international consensus of the European Allergy White Paper, require the same
      procedure in clinical practice. Many patients with different allergic skin
      diseases are treated inappropriately, some are tested in active phase of the
      disease, during anti-allergic therapy, and some are administered corticosteroids
      and antihistamines longer than necessary. Sometimes, the treatment of emergencies
      requires a person experienced in intensive care medicine. However, any physician
      might be responsible for the treatment of acute symptoms in his office, and thus
      has to know the modalities and relevant drugs and treatment essentials.
      Anaphylactic reactions are rare, but every physician should be prepared for the
      worst. Due knowledge of the correct management should be a must for all of us.
      The most common emergencies require emergency treatment and diagnostic procedures
      upon disease regression.

PMID- 22359877
TI  - [Increasing incidence of angioedema without urticaria--clinical features].
AB  - The causes of angioedema (AE), a self-limited, localized swelling of subcutaneous
      tissue or mucosa unaccompanied by urticaria, are diverse. The commonly applied
      label of "allergic" is frequently wrong and standard anti-allergic therapy can be
      ineffective. Types of AE could be categorized according to mediators which
      mediate vascular leakage: bradykinin AE (hereditary, acquired, angiotensin
      converting enzyme inhibitor (ACEi)-related), histamine AE (allergic etiology),
      and various mediators mediated AE (pseudoallergic reaction to non-steroidal anti
      inflammatory drugs). Idiopathic AE is a poorly understood syndrome. The growing
      relevance of AE without urticaria has been highlighted; angioedema is the most
      common cause of hospital admission among all acute allergic diseases. The
      diagnosis of AE is based on the presence of family history (hereditary), absence
      of family history with the onset during or after the fourth decade of life
      (acquired C1lnh deficiency), and treatment with ACEi (ACEi-related angioedema).
      About 0.1%-0.7% of patients taking ACEi develop angioedema as a well-documented
      but still frequently unrecognized side effect of drugs. Laboratory diagnosis is
      enabled by measuring serum levels of C1lnh antigen or C1lnh function. Type 1
      (hereditary angioedema (HAE) was diagnosed when both antigenic and functional
      levels of C1lnh were below 50% of normal, and type 2 when functional levels of
      C1lnh were low, along with antigenic levels normal or higher. ACEi-related AE is
      diagnosed when AE recurs during therapy and disappears upon withdrawal. Symptoms
      may appear several years after therapy introduction. Severe acute attacks should
      be treated with C1lnh concentrate and icatibant, a selective and specific
      antagonist of bradykinin B2 receptors. Prophylaxis with attenuated androgens
      (danazol, stanazolol, oxandrolone) is effective in preventing symptom
      development.

PMID- 22359878
TI  - [Asthma phenotypes and disorder of the immune system homeostasis].
AB  - Many regulatory pathways involved in the pre- and post-IgE synthesis signaling
      have been elucidated and effects of numerous mediators included in allergic
      cascade understood; however, asthma remains a clinical and scientific problem.
      Immune system is being confused by modern civilization, producing complex
      interaction among epigenetic regulation, variable extrinsic factors and various
      combinations of paired effects, i.e. genes, antigens and life periods. It is
      therefore necessary to answer the question of how to ensure an adequate level of
      necessary immune stimuli at the time of intensive immune system development until
      age 6. Advances in immunology have enabled full asthma control but not cure in a
      great proportion of patients. Therefore, researchers have focused on particular
      features of specific inflammatory asthma subtypes, i.e. eosinophilic,
      neutrophilic, mixed and asthma without inflammatory cells. Therapeutic response
      to inhalant and systemic corticosteroids in a particular subtype is also
      investigated. The Global Initiative for Asthma Guidelines, developed by the group
      of experts and regularly updated with new scientific concepts, are available in
      clinical routine. The guidelines provide a useful framework for the choice of
      drugs and dosage, but they cannot replace clinician's evaluation in individual
      approach to patient. However, current conditions still cannot ensure personalized
      asthma therapy.

PMID- 22359879
TI  - [Reactions to insect stings and bites].
AB  - Reaction to insect sting and bite may be local, such as erythema, edema and
      pruritus, or systemic, such as anaphylactic reaction. Diagnosis can be made by
      patient history, clinical picture, skin testing, total and specific IgE level,
      and provocation test. Local reactions are treated with cold compresses, topical
      corticosteroids and oral antihistamines. Oral and intramuscular antihistamines
      and corticosteroids are used for the treatment of mild systemic reactions, and in
      severe reaction epinephrine injections are added. Hyposensitization is indicated
      in patients with severe systemic reaction, positive skin tests and high level of
      specific IgE antibodies.

PMID- 22359880
TI  - [Allergic diseases and smoking].
AB  - Cigarette smoking is a major risk to the overall burden of disease in developed
      countries. Smoking influences disease development, disease outcome and
      therapeutic success. Cigarettes with low tar, which do less harm, do not exist,
      nor there is a safe level of smoking. Passive smoking is involuntary inhalation
      of tobacco smoke. Environmental tobacco smoke is the second most common cause of
      carcinogen exposure. Passive smoking, whether prenatal or postnatal in children,
      increases the likelihood of asthma, similar as in adults. Active smoking
      increases total immunoglobulin E (IgE) level and inflammatory cell infiltration,
      especially eosinophils. Tobacco smoking increases bronchial hyperreactivity.
      Clinical picture of asthma in smokers is more severe in terms of symptoms, with
      more frequent exacerbations and invasive intubation with increased mortality rate
      than in asthmatics nonsmokers. Smokers have a higher prevalence of allergic
      rhinitis and atopic dermatitis.

PMID- 22359881
TI  - [Epidemiology of allergic diseases].
AB  - The article gives a critical review of the main epidemiological features of
      allergic diseases, their frequency, distribution and etiologic background as well
      as the possibilities of prevention and control, based on current literature.
      Statistical data for Croatia, collected by the Croatian National Institute of
      Public Health, are used to present actual epidemiological situation in Croatia.
      Basic descriptive epidemiological methods were used to express age and sex
      distribution, etc. In comments and review of preventive measures, our own
      epidemiological experiences and experience acquired on creating the national
      programs of health measures were used. The genesis of allergies usually implies
      the influence of various potent environmental allergens such as proteins or
      smaller molecules attached to proteins (haptens) through repeat or continuous
      exposure by contact, alimentary or respiratory route, and parenteral route as
      most efficient (mucous membrane exposure is similar to parenteral exposure). In
      addition, almost all substances from our environment may, under certain
      circumstances, become allergens and produce allergic reaction. Individual
      constitution that is inherited also plays a role. Allergic diseases are present
      all over the world, however, with variable frequency. Response to an allergen is
      generally the same, causing distinct allergic diseases like urticaria,
      anaphylactic shock, asthma, etc., while the main allergens can be different. It
      is estimated that 30%-40% of all people have some type or manifestation of
      allergy. According to our Institute data, in Croatia hospitalization was mostly
      required for allergic urticaria and allergic asthma, followed by Quincke's edema.
      Optimal treatment and appropriate healthcare structure are essential for
      efficient control and prevention of allergic diseases. The main direct elements
      are as follows: well organized emergency service for anaphylactic and other
      severe conditions; health education expected from all levels of healthcare
      system; allergology outpatient services available; and sufficient hospital
      capacities. An indirect yet important element is optimal drug prescribing and
      usage practice. Other specific public health measures include: pollen air
      concentration monitoring by public health institutes; information on particular
      allergen presence and intensity via public media; and control of potential
      allergen emission into the environment, especially air. People will, as always,
      find ways to adapt themselves and cope with allergies, with medical profession
      helping them by identifying the reasons causing allergic diseases and developing
      successful measures of treatment, prevention and control.

PMID- 22359882
TI  - [Food hypersensitivity in children].
AB  - Food hypersensitivity affects children and adults with an increasing prevalence,
      and is therefore an important public health problem in the majority of developed
      countries. Moreover, self-reported reactions to food are of several times higher
      prevalence, compared to hypersensitivity diagnosed following well established
      evidence-based diagnostic guidelines. In children, allergic food reactions are
      more common compared to non-allergic food hypersensitivity reactions, and 90% of
      them are caused with only 8 food allergens: cow's milk, soya, egg, fish,
      shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge
      tests with the potentially offending food allergens. Concerning other, more
      conservative diagnostic procedures, negative serology and negative skin-prick
      tests can exclude IgE-mediated food allergy, but positive tests, due to high rate
      of false positive reactions are not sufficient for diagnosis. Strict dietary
      avoidance of incriminated allergens is the only well established management
      strategy. However, this should be applied only if food allergy is well documented
      - following the exposition tests. Introducing elimination diet in a paediatric
      population, particularly with the elimination of multiple foods, could cause
      inappropriate growth and disturb organ maturation. Concerning allergy prevention,
      avoidance of allergens is not efficacious either during pregnancy and lactation
      or weaning period, and is therefore, not recommended neither as a population
      preventive measure, nor in children at risk.

PMID- 22359883
TI  - [Allergic rhinitis in children].
AB  - Allergic rhinitis is the most prevalent form of chronic rhinitis in children. It
      is driven by allergic inflammation and is commonly associated with other atopic
      diseases such as asthma and atopic eczema. The main allergens are primarily
      aeroallergens: house dust mite, and tree, grass and weed pollen. It is, however,
      not exceptional to experience symptoms of allergic rhinoconjunctivitis in
      conjunction with food allergy and oral food allergy syndrome, especially in
      infants and toddlers. Allergic rhinitis is often associated with allergic asthma,
      either preceding it, or developing later and making it more difficult to treat.
      The mainstay of treatment is exposure prophylaxis, antihistamines, leukotriene
      antagonists and intranasal corticosteroids. Allergic rhinitis is one of the prime
      indications for specific allergen immunotherapy, which may have a preventive
      effect on the development of asthma. Allergic rhinitis associated with
      intermittent or mild persistent asthma may be a good indication for concomitant
      combination treatment with antihistamines and leukotriene antagonists. Intranasal
      corticosteroids should not be withheld in more severe forms. Shortterm (up to 3
      months) use of intranasal corticosteroids has not been associated with any
      significant local or systemic side effects.

PMID- 22359884
TI  - [Asthma in children].
AB  - Asthma is the most common chronic disease in childhood characterized by chronic
      bronchial inflammation of variable intensity accompanied by spontaneous or drug
      reversible airflow obstruction. The onset of asthma, clinical presentation and
      response to therapy are influenced by numerous genetic and environmental factors.
      Asthma in childhood is characterized by its heterogeneity in terms of possible
      etiology, degree of inflammation and airway obstruction, lung function as well as
      the natural course of disease that may persist and continue to adulthood.
      Protective factors linked to early life experiences have also been delineated
      which may impact the development of asthma. Pathophysiological mechanisms of
      allergic reaction as an excessive inflammation driven by T-helper-2 (Th2)
      immunity, offer poor understanding of the heterogeneity of clinical disease. A
      recently introduced approach defines asthma as a syndrome that comprises of
      several subtypes or endotypes based on entirely novel pathways to disease. Timely
      diagnosis and adequate treatment are necessary to prevent irreversible airway
      remodeling and consequent decrease in pulmonary function.

PMID- 22359885
TI  - [Rhinitis in adults].
AB  - Rhinitis is a very common disorder caused by inflammation or irritation of nasal
      mucosa. Dominant symptoms are nasal obstruction; however, in some patients, runny
      nose, excessive sneezing or nasal itch may be the most bothersome symptoms. The
      most common causes of nasal inflammation are viral infections and allergic
      response to airborne allergens. Response to irritants may cause similar symptoms,
      although signs of inflammation may not always be present. Viral rhinitis is
      lasting up to 10 days and it is part of the common cold syndrome. In short-lived
      rhinitis, lasting for 7 to 10 days, sometimes it is not easy to differentiate
      between the potential causes of the disorder, if general symptoms of infection
      like fever and malaise are not present. In long-living rhinitis, it is important
      to differentiate between infectious, allergic, non-allergic non-infectious
      rhinitis, and chronic rhinosinusitis. Itch and ocular symptoms are more common in
      allergic rhinitis, while other symptoms like nasal obstruction, rhinorrhea and
      sneezing may affect patients with allergic and non-allergic rhinitis. Patients
      with allergic rhinitis often have symptoms after exposure to irritants,
      temperature and humidity changes, like patients with non-allergic rhinitis, and
      such exposure may sometimes cause more severe symptoms than exposure to
      allergens. Sensitivity to a non-specific trigger is usually called non-specific
      nasal hyperreactivity. Allergic rhinitis occurs due to immunoglobulin E (IgE)
      interaction with allergen in contact with nasal mucosa in a sensitized patient.
      Sensitization to certain airborne allergen, like pollens, dust, molds, animal
      dander, etc. usually occurs in families with allergy background, which is helpful
      in making diagnosis in patients who have rhinitis in a certain period of the
      year, or aggravation of nasal symptoms occurs in the environment typical of
      certain allergen. The diagnosis is clinically confirmed by proving sensitivity to
      certain allergen on skin prick test, and by proving specific antibody IgE in
      patient serum. Allergic rhinitis is categorized according to sensitivity to
      allergens that occur seasonally, like pollens, or to allergens that are present
      all year round, like house dust mite, molds and animal dander, into seasonal and
      perennial allergic rhinitis. Allergy to pollens causes the same mechanism of
      inflammation in response to allergens, which is the result of allergen binding to
      specific IgE antibody; however, patients with pollen allergy usually complain
      more of sneezing and runny nose, whereas patients with allergy to perennial
      allergens more often complain of obstruction, with the episodes of sneezing and
      runny nose occurring only when exposed to higher concentrations of allergens
      (house cleaning, around pets). Treatment includes avoidance of allergens, medical
      treatment and immunotherapy (allergy vaccines, tablets with allergens). Avoidance
      of allergens means reduction of environmental allergen load to the respiratory
      system including workplace, which is not easy to accomplish. Medical treatment is
      usually necessary to control symptoms, and it includes antihistamines, nasal or
      in tablets, and nasal glucocorticoids (steroids). Antihistamines should be second
      generation, which do not cause sedation, and such treatment shows more efficacy
      on runny nose, sneezing and nasal itch than on nasal stuffiness. Nasal steroids
      are more potent in improving nasal patency than antihistamines, and are at least
      as potent in the control of all other nasal and ocular symptoms. Nasal patency
      may be improved by nasal or oral decongestants, but such treatment should be
      reduced to as short period as possible, since after several days of using nasal
      decongestants rebound congestion may occur and patients will need nasal
      decongestants to improve nasal airways even when allergens are not around
      anymore.

PMID- 22359886
TI  - [Management of allergic diseases].
AB  - Treatment of allergic diseases is based on the direct impact of the three main
      target areas: mast cell stabilization, preventing the release of mediators, and
      specific immune response. It is essential to prevent exposure to the causative
      allergen. Treatment is applied systemically or topically. Local treatment is
      preferred in many allergic skin diseases and asthma, when it is effective.
      Associated inflammatory components must also be treated, especially in the
      treatment of asthma, and not just with symptomatic agents. There is also anti
      inflammatory and symptomatic treatment. Corticosteroids and antihistamines are
      the most commonly used drugs. Some subchapters list the benefits of individual
      drugs for organ systems, by their generic names. Mast cell stabilizers, beta
      agonists, antihistamines, leukotriene antagonists, quinine antagonists,
      immunotherapy and omalizumab (anti-IgE antibody) are essential in the treatment
      of allergy.

PMID- 22359887
TI  - [The role of immunotherapy in the prevention of allergic diseases].
AB  - Immunotherapy through repeated administration of allergens and augmentation of
      doses (hyposensibilization) with the purpose of decreasing the severity of type I
      allergic reactions or even its complete elimination is known already for a longer
      period of time. This type of therapy is especially beneficial in allergies to
      Hymenoptera venom, allergic rhinoconjunctivitis, allergic asthma and is
      implemented in patients with previously proven allergy to appropriate allergens
      (insects, pollen, house dust mite, pet dander and other). The most common form of
      therapy is subcutaneous immunotherapy which includes a series of injections
      containing specific allergens (allergy vaccines) with increasingly larger doses
      administered subcutaneously during a period of 3-5 years. There are also other
      forms of immunotherapy (for instance sublingual immunotherapy) although these are
      less effective. Repetition of the hyposensibilization procedure leads to further
      reduction in severity of allergy disease in the majority of patients. The
      efficacy of immunotherapy is also proven by a lower risk of allergic rhinitis
      patients developing asthma as well as by prevention of new sensibilizations.

PMID- 22359888
TI  - [Diagnostic criteria for occupational allergic diseases].
AB  - Exposure to allergens at workplace is more frequent nowadays. The most common
      occupational allergic diseases with proven association of the disease and
      occupational exposure determining damage to function and/or morphology and
      confirming the disease by diagnostic workup are occupational allergic rhinitis,
      occupational asthma, allergic alveolitis and allergic contact dermatitis. This
      paper describes diagnostic algorithms of differential diagnosis to confirm the
      diagnosis of occupational disease and to take measures for preserving functional
      capacity of the employees.

PMID- 22359889
TI  - [Epidemiological characteristics of thyroid cancer in Dalmatia, Croatia].
AB  - OBJECTIVES: To determine epidemiological characteristics of thyroid carcinoma in
      Dalmatia, and to compare the incidence rate in Dalmatia with that in Croatia.
      STUDY DESIGN: Retrospective epidemiological study. SUBJECTS AND METHODS:
      Epidemiological indicators of thyroid carcinoma were compared between Dalmatia
      and Croatia as a whole, while some epidemiological indicators were compared with
      the characteristics of persons suffering from thyroid carcinoma in Croatia. The
      study included 651 persons suffering from and/or operated for thyroid carcinoma
      in Dalmatia between 1997 and 2006. Data were obtained from case histories,
      including the results of histopathologic analysis. The area of Dalmatia includes
      Zadar, Sibenik-Knin, Split-Dalmatia and Dubrovnik-Neretva counties (overall
      861,060 inhabitants, surface 11,960 square kilometers). RESULTS: The incidence of
      thyroid carcinoma in Dalmatia ranged from 5.2 (1997) to 10.2 per 100,000
      inhabitants (2006). The mean age adjusted incidence rate of thyroid cancer in the
      last 10 years was 8.1 in Croatia and 9.32 per 100,000 inhabitants in Dalmatia.
      All incidence rates observed (Europe and world-age standardized rates, crude
      incidence, incidence based on research) showed a rising trend and were
      significantly higher in Dalmatia than in Croatia. According to sex structure, in
      both study areas thyroid cancer affected predominantly women, who had four times
      more chances of falling ill. In Dalmatia, in the overall sample, women accounted
      for 81.4% of all patients. In Dalmatia, papillary thyroid carcinoma was diagnosed
      in 80.0% of the overall sample. The median age of newly diagnosed thyroid cancer
      patients was 50 in Dalmatia. There was no statistically significant sex
      difference in the prevalence of histologic types of thyroid carcinoma in Dalmatia
      (P=0.318). In both sexes, papillary carcinoma was the most common type, followed
      by follicular, medullary and anaplastic thyroid carcinomas. CONCLUSION: The
      incidence rate of thyroid cancer showed a rising trend and was significantly
      higher in Dalmatia than in Croatia. Epidemiological characteristics of thyroid
      gland carcinoma in Dalmatia were consistent with the reported characteristics of
      this carcinoma in iodine-sufficient areas: papillary carcinoma was prevalent and
      the papillary to follicular carcinoma ratio was 6.4:1.

PMID- 22359890
TI  - [Histologic assessment of tissue healing of hyaline cartilage by use of
      semiquantitative evaluation scale].
AB  - INTRODUCTION: Articular cartilage is an avascular and aneural tissue lacking
      lymph drainage, hence its inability of spontaneous repair following injury. Thus,
      it offers an interesting model for scientific research. A number of methods have
      been suggested to enhance cartilage repair, but none has yet produced significant
      success. The possible application of the aforementioned methods has brought about
      the necessity to evaluate their results. The objective of this study was to
      analyze results of a study of the effects of the use of TGF-beta gene transduced
      bone marrow clot on articular cartilage defects using ICRS visual histological
      assessment scale. METHODS: The research was conducted on 28 skeletally mature
      sheep that were randomly assigned to four groups and surgically inflicted femoral
      chondral defects. The articular surfaces were then treated with TGF-beta1 gene
      transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP
      group), untransduced bone marrow clot (BM group) or left untreated (NC group).
      The analysis was performed by visual examination of cartilage samples and results
      were obtained using ICRS visual histological assessment scale. The results were
      subsequently subjected to statistical assessment using Kruskal-Wallis and Mann
      Whitney tests. RESULTS: Kruskal-Wallis test yielded statistically significant
      difference with respect to cell distribution. Mann-Whitney test showed
      statistically significant difference between TGF and NC groups (P = 0.002), as
      well as between BM and NC groups (P = 0.002 with Bonferroni correction).
      DISCUSSION: Twenty-six of the twenty-eight samples were subjected to histologic
      and subsequent statistical analysis; two were discarded due to faulty histology
      technique. Our results indicated a level of certainty as to the positive effect
      of TGF-beta1 gene transduced bone marrow clot in restoration of articular
      cartilage defects. However, additional research is necessary in the field. One of
      the significant drawbacks on histologic assessment of cartilage samples were the
      errors in histologic preparation, for which some samples had to be discarded and
      significantly impaired the analytical quality of the others. Defects of
      structures surrounding the articular cartilage, e.g., subchondral bone or
      connective tissue, might also impair the quality of histologic analysis.
      Additional analyses, i.e. polarizing microscopy should be performed to determine
      the degree of integration of the newly formed tissue with the surrounding
      cartilage. The semiquantitative ICRS scale, although of great practical value,
      has limitations as to the objectivity of the assessment, taking into account the
      analytical ability of the evaluator, as well as the accuracy of semiquantitative
      analysis in comparison to the methods of quantitative analysis. CONCLUSION:
      Overall results of histologic analysis indicated that the application of TGF
      beta1 gene transduced bone marrow clot could have measurable clinical effects on
      articular cartilage repair. The ICRS visual histological assessment scale is a
      valuable analytical method for cartilage repair evaluation. In this respect,
      further analyses of the method value would be of great importance.

PMID- 22359891
TI  - [Virologic and epidemiological characteristics of non-polio infection in Croatia
      over a ten-year period (2000-2009)].
AB  - AIM: The aim of the present study was to show the virologic and epidemiological
      characteristics of non-polio enterovirus (NPEV) infection over a ten-year period
      in Croatia. METHODS: During the 2000-2009 period, the Laboratory for
      Enteroviruses, Croatian Public Health Institute analyzed 2754 clinical samples
      collected from 1880 patients with a clinical picture of enteroviral infection.
      The diagnosis of enteroviral infection was confirmed by virus isolation in cell
      culture. Viruses were typed using indirect immunofluorescence and/or
      neutralization assay. RESULTS: NPEV was proven in 394 (21%) of 1880 patients.
      Males were more commonly infected than females, at a ratio of 1.8:1, while the
      number of infected cases was highest among preschoolers and schoolchildren.
      Patients with isolated NPEV were most frequently diagnosed with aseptic
      meningitis (234/394; 59.4%). Infections were most commonly caused by echoviruses
      (218/394; 55.3%), followed by Coxsackie B (126/394; 32.0%) and Coxsackie A
      (31/394; 7.9%) viruses, rarely by echovirus 22 - parechovirus 1 (16/394; 4.1%)
      and enterovirus 71 (3/394; 0.8%). In most cases, echoviruses of the following
      serotypes were proven: 6, 9, 11, 13, 14, 18 and 30 (45/218, 21%; 14/218, 6.4%;
      18/218, 8.3%; 15/218, 6.9%; 11/218, 5.0%; 55/218, 25.2% and 42/218, 19.3%), while
      serotypes 2, 3, 4, 5, 7, 12, 20, 21,25 and 26 were evidenced in a minority of
      patients or individual cases. Coxsackie B5 was the predominant serotype among
      Coxsackie B viruses (50/126, 40%), while Coxsackie A9 was most common Coxsackie A
      virus (26/31, 84%). Coxsackie B5 and B4 viruses were continually detected during
      the study period and appeared more frequently every four to five years. The most
      common echovirus isolate was echovirus 18, detected continually between 2000 and
      the outbreak year of 2006. Echovirus 6 and echovirus 30 were also isolated
      continually with peaks in 2002 and 2008, or 2002, 2006 and 2008. CONCLUSION: The
      results of this study pointed to a specific pattern of the occurrence of certain
      NPEV serotypes in Croatia. The epidemic pattern (echovirus 18 and Coxsackie 81)
      was characterized by peaks with an elevated number of isolations in given years.
      Contrary to this, endemic viruses were isolated in similar counts every year
      (Coxsackie B3), or manifested milder epidemic peaks every few years (echoviruses
      30 and 6, Coxsackie B4 and B5). Data on NPEV infections, given their serotype and
      specific pattern of occurrence, contribute significantly to prompt diagnostic,
      clinical and epidemiological response to NPEV infections.

PMID- 22359892
TI  - [Lower levels of HDL2 cholesterol are associated with microalbuminuria in
      patients with type 1 diabetes].
AB  - OBJECTIVE: Lipoproteins may contribute to diabetic nephropathy. Although elevated
      total HDL cholesterol levels have been shown to protect from coronary artery
      disease and nephropathy in many studies, HDL can be subdivided into at least two
      major subclasses, which are thought to differ in the ability to protect against
      atherosclerosis. The objective of this study was to determine the relationship
      between serum lipids and HDL subclasses with albuminuria in patients with type 1
      diabetes. METHODS: We analyzed lipid profiles of 259 patients with type 1
      diabetes and normal thyroid function. Patients were classified as
      normoalbuminuric (albumin excretion rate < 30 mg/24 h, n = 215) and
      microalbuminuric (albumin excretion rate 30-300 mg/24 h, n = 44) in at least two
      urine collections. None showed signs of adrenal, thyroid, renal or cardiovascular
      disease, or received drugs, apart from insulin, that could attenuate glucose
      metabolism, serum lipids or renal function. Total, LDL, HDL, HDL2, HDL3, VLDL
      cholesterol and triglycerides were measured by an enzymatic colorimetric method
      and urinary albumin concentration was determined by an immunoturbidimetric assay.
      RESULTS: Patients with microalbuminuria had higher levels of total cholesterol
      (5.07 vs. 5.02 mmol/L, Mann Whitney=6874, P = 0.666), LDL cholesterol (2.81 vs.
      2.80 mmol/L, Mann Whitney = 6964, P = 0.778), VLDL cholesterol (0.57 vs. 0.48
      mmol/L, Mann Whitney = 6268, P = 0.151) and triglycerides (1.27 vs. 1.08 mmol/L,
      Mann Whitney = 6283, P = 0.158), and lower levels of HDL cholesterol (1.68 vs.
      1.73 mmol/L, Mann Whitney = 6501, P = 0.293) and HDL3 cholesterol (1.15 vs. 1.16
      mmol/L, Mann Whitney = 6991, P = 0.812); however, these differences were not
      statistically significant. In contrast, HDL2 cholesterol levels were
      significantly lower in those who had microalbuminuria compared with those who had
      normoalbuminuria (0.50 vs. 0.57 mmol/L, Mann Whitney = 5600, P = 0.01).
      CONCLUSIONS: Microalbuminuria is the earliest clinical indicator of diabetic
      nephropathy. Clustering of coronary artery disease with nephropathy has been
      shown previously in patients with type 1 diabetes. Specific effects of HDL
      subclasses on cardiovascular disease have also been observed, i.e. a protective
      effect of large HDL subfractions (HDL2) and an increased risk for small HDL
      particles (HDL3). Results of the present study showed that lower levels of HDL2
      cholesterol were associated with microalbuminuria in patients with type 1
      diabetes. Whether higher HDL2 cholesterol levels may be protective against the
      development of microalbuminuria in patients with type 1 diabetes can only be
      determined in long-term studies.

PMID- 22359893
TI  - [Leprosy--today forgotten in Croatia?].
AB  - Leprosy is an infectious skin disease caused by Mycobacterium leprae, which
      predominantly affects the skin, peripheral nerves and mucous membrane of the
      upper respiratory tract and oral cavity. In spite of today's efficient treatment,
      leprosy represents a public health problem in some countries of the world. It is
      estimated that 12 to 15 million patients are currently affected in the world.
      Leprosy ravaged across Europe, including Croatia, for centuries, so this paper
      provides a few historical facts on leprosy in Croatia. In 1956, the last case of
      leprosy was recorded in Blizna, a small village near Trogir, which was considered
      an endemic region in the Republic of Croatia. Although there is no indigenous
      leprosy nowadays in Croatia, there is a possibility of the disease re-emergence
      from tourists or crew members from large vessels, or from the infected persons
      returning to Croatia from abroad. Therefore, Croatian physicians, especially
      dermatovenereologists, must be familiar with the basics of the disease;
      therefore, this article points out the clinical picture, classification and basic
      principles of pathogenesis and treatment of the disease.

PMID- 22359894
TI  - [Clinico-epidemiological analysis of choroidal melanoma in Split Area, Croatia].
AB  - Choroidal melanoma is the most common primary intraocular malignant tumour in
      adults. The aim of the study was to examine epidemiological characteristics of
      choroidal melanoma in Split-Dalmatia County from 1990 to 2009. In this
      retrospective study, data on 46 patients from medical documentation of the
      University Department of Ophthalmology, Split University Hospital Center, were
      analyzed. According to 2001 census, the Split-Dalmatia County population was
      467,676 inhabitants. The incidence of choroidal melanoma was 0.49 per 100,000
      inhabitants, which is somewhere in the middle of the incidence between south and
      north Europe. Choroidal melanoma most commonly appeared in the 7th decade of
      life. The average dimensions of choroidal melanoma (basis x height) were 13.4 x
      8.0 mm. Histopathologic findings according to Callender classification showed the
      following types of melanoma: epithelioid cell type 8%, spindle cell type 40%, and
      mixed type 52%. The most common forms of therapy were enucleation 47.8% and
      brachytherapy 28.3%, which means that patients presented relatively late when
      choroidal melanoma advanced in size. The Split-Dalmatia County has 1/10 of the
      Croatian population, so it could be supposed that approximately 25 new cases of
      malignant melanoma of the choroid are discovered annually in Croatia. For early
      detection of the disease, regular and complete checkups are necessary, especially
      in presbyopic population. Study results enabled better evaluation of the disease
      and better planning of ophthalmologic service in the treatment of this serious
      eye disease.

PMID- 22359895
TI  - [Epidemiological characteristics of acute lymphoblastic leukemia in children from
      Tuzla Canton].
AB  - This study was undertaken to determine epidemiological characteristics of acute
      lymphoblastic leukemia (ALL) in children aged 0-14 years from Tuzla Canton,
      during a 13-year period (1995-2007). This retrospective study analyzed patient
      medical records from University Department of Pediatrics, Tuzla University
      Clinical Center, as well as documentation of other medical facilities providing
      additional diagnostic and therapeutic treatment to these patients. Records on the
      population of children during the study period were obtained from Federal
      Department of Statistics. ALL was diagnosed in 41 children, 27 (66.0%) male and
      14 (34.1%) female. The mean incidence rate for both sexes was 3.3/100,000 (2.3
      4.4). It was higher in boys (4.2/100,000) than in girls (2.3/100,000). The
      highest incidence rate was recorded in 2002 (7.6/100,000). Study results provided
      reliable insight into the epidemiological characteristics of ALL in children from
      Tuzla Canton and proved useful for planning a pediatric health care program in
      the area.

PMID- 22359896
TI  - [Secondary (AA) amyloidosis in Crohn's disease].
AB  - Amyloidosis is a clinical entity that results from deposition of an extracellular
      protein material that causes disruption in normal architecture and impairs
      function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but
      serious complication that occurs in the context of cancer, chronic inflammation
      and chronic infectious diseases, including inflammatory bowel disease, mainly
      long-standing Crohn's disease. Renal failure is the most common clinical
      presentation of AA, ranging from nephrotic syndrome and impaired renal function
      to renal failure, with a potential for high morbidity. The incidence of the
      association of secondary amyloidosis in patients with Crohn's disease has been
      reported to be 0.5%-8%. We present a case of a 39-year-old male patient diagnosed
      with Crohn's disease at age 21 and submitted to right hemicolectomy because of
      ileus 17 years before. Thereafter, he was treated with corticosteroids for 15
      years and with azathioprine for a short period; in the last three years he was on
      therapy with mesalazine alone. He was hospitalized due to worsening clinical
      condition and re-evaluation of the underlying disease. Physical examination
      revealed marked peripheral edema in both lower extremities. Endoscopic and
      radiographic examinations confirmed the underlying disease activity. Laboratory
      tests showed an increase of inflammatory reactants, anemia, hypocalcemia, and
      severe hypoalbuminemia and hypoproteinemia. He had proteinuria over 24 g/L and
      creatinine clearance of 66 mL/min, falling within second grade of chronic kidney
      disease. Renal biopsy was performed for evaluation of renal insufficiency with
      nephrotic range proteinuria. Congo red staining showed the presence of
      characteristic amyloid deposition; deposits immunoreacted with the antibody
      against amyloid A protein, confirming the diagnosis of secondary amyloidosis. The
      patient was suggested active induction treatment with corticosteroids and
      azathioprine to achieve remission of Crohn's disease, thereafter treatment with
      infliximab, but he did not consent with this therapy at that time. Studies with
      infliximab have demonstrated a decrease in SAA circulating levels and
      proteinuria, as well as stabilization of renal function. Amyloidosis is
      frequently described as a major cause of death in patients with Crohn's disease,
      with long-term mortality between 40% and 60%. Various therapeutic attempts such
      as azathioprine, colchicine, dimethyl sulfoxide, infliximab, and elemental diets
      have been tried but there is no definite treatment for secondary amyloidosis in
      Crohn's disease. Kidney transplantation may offer the best prospects for patients
      with Crohn's disease who develop amyloidosis and end-stage renal failure.

PMID- 22359897
TI  - [Ileus caused by metastasis of cutaneous malignant melanoma: case report].
AB  - In this case report we describe rare metastatic appearance of cutaneous malignant
      melanoma ( MM) in small intestine followed by clinical appearance of acute
      surgical abdomen. A 42-year old women operated in our hospital in April 2009. due
      to unusual naevus on her right arm. Pathologicaly it was MM grossly 1.5 cm,
      microscopically Breslow 11 mm, Clark's level IV (T4), number of mitosis 1.4 per
      mm2, without ulcerations. She was sent to continue treatment at the National
      Referal Center for Melanoma in KB "S. milosrdnice" Zagreb, Croatia. A month later
      wider excision (3 cm free margin) and sentinel lymph node biopsy (SLNB) was made
      there followed by axillary lymphadenectomy due to positive axillary finding. She
      received six cycles of chemotherapy. She arrived in our hospital in May 2010,
      under clinical picture of small intestine ileus and acute surgical abdomen. After
      preparation she was operated the same day. The cause of ileus was metastasis of
      MM in the small interstine. We made intestinal resection with termino-terminal
      anastomosis. The patient was released to home care ten days after operation
      without any complication. This case report demonstrates rarely described case of
      MM metastasis in the small intestine found causing ileus.

PMID- 22359898
TI  - [Resuscitation by direct heart massage in the history of surgery and anesthesia
      of Bjelovar hospital].
AB  - This historical review presents cases of direct heart massage in patients with
      intraoperative cardiac arrest performed at Department of Surgery, Bjelovar
      General Hospital. Out of five cases recorded in the 1960-1970 period,
      resuscitation proved successful in two patients, but one patients living normal
      life free from any subsequent complications. The patient critical general
      condition, comorbidities and anesthesiology incidents as the possible causes of
      cardiac arrest are discussed, and the staffing and logistic problems encountered
      in a small-town hospital are presented.

PMID- 22359899
TI  - [Kidney transplantation].

PMID- 22359900
TI  - [Preparation of highly HLA-sensitized patient for heart transplantation: first
      documented case in Croatia].
AB  - The presence of human leukocyte antigen (HLA) poses a significant therapeutic
      challenge in solid organ transplantation. Sensitized patients (panel reactive
      antibody, PRA > 10%) receiving a heart transplant are at an increased risk of
      developing several clinical syndromes that influence short-term, and possibly
      also long-term patient survival. We present a case of immune system modulation in
      a highly sensitized patient awaiting heart transplantation. To our knowledge,
      this is the first case of desensitization therapy in solid organ transplantation
      done in Croatia. The patient with decompensated primary dilated cardiomyopathy
      received left ventricular assist device as a bridge to heart transplantation. Pre
      transplantation evaluation revealed the presence of fungal pneumonia and high
      sensitization to HLA antibodies (PRA 97%). Desensitization protocol consisted of
      mycophenolate mofetil, tacrolimus, intravenous immune globulin and preoperative
      plasmapheresis along with previously initiated antifungal therapy. We withheld
      the application of rituximab until after resolution of pneumonia, but our
      protocol lowered PRA to 6% even without it. Unfortunately, during the next
      several weeks, a suitable donor was not found and our patient died form
      multiorgan failure. Avoidance of allosensitization by early referral to
      transplantation center, early transplantation, and avoidance of transfusions are
      very important when treating a potential transplant recipient. In this way,
      waiting time to transplantation, development of posttransplantation complications
      and mortality are reduced.

PMID- 22359901
TI  - [Lymphocele and renal transplantation].
AB  - Lymphoceles are a well-known surgical complication of kidney transplantation. We
      retrospectively analyzed patients with lymphoceles among our renal transplant
      recipients. During the last 39 years, we performed 922 renal transplantations.
      Lymphoceles were diagnosed and treated in 45 (4.9%) patients. We used the
      following methods: percutaneous drainage with instillation of povidone-iodide in
      36 (80%), percutaneous drainage with instillation of tetracycline in one (2.2%),
      percutaneous aspiration in four (8.9%) and surgical treatment in four (8.9%)
      patients. In all four (8.9%) patients with relapse, secondary procedure was
      successful. In total, open surgery was done in five (11.1%) and laparoscopy in
      four (8.9%) patients. Percutaneous drainage of lymphoceles, with or without the
      instillation of a sclerosant, is the first-line treatment. Laparoscopic
      fenestration of lymphoceles has become an alternative to percutaneous drainage,
      especially in case of post-drainage relapse.

PMID- 22359902
TI  - [Outcome of renal transplantation after tacrolimus switch to cyclosporine].
AB  - Calcineurin inhibitors play the key role in current immunosuppressive therapy in
      transplantation medicine. We present our experience with tacrolimus as
      immunosuppressive therapy and the reasons for replacing tacrolimus with
      cyclosporine in some patients. We monitored graft function, serum lipid levels,
      and blood glucose concentration before and after immunosuppressant switch. The
      most common reason for change of immunosuppressive therapy was insulin dependent
      hyperglycemia; calcineurin inhibitor nephrotoxicity was the reason for switching
      immunosuppressive therapy in a small number of patients; and in one patient, the
      reason for immunosuppressive therapy switching was BK virus infection. Blood
      glucose normalized soon after the introduction of cyclosporine in the treatment.
      Monitoring of laboratory tests before and after immunosuppressive therapy
      switching showed the graft function to have remained unchanged.

PMID- 22359903
TI  - [Outcome of renal transplantation in patients with chronic virus hepatitis].
AB  - The objective is to present results of renal transplantation in patients with end
      stage renal disease and chronic virus C/B hepatitis. We retrospectively reviewed
      outcome of transplantation in patients having received renal allograft from 1985
      to 2009 at Zagreb University Hospital Center: graft function, graft and patient
      survival, hepatic function, and complications of transplantation, i.e. episodes
      of acute rejection, manifestation of diabetes mellitus, and proteinuria. There
      were 91 patients, 50 men and 41 women, mean age 40.9. Patients were previously
      treated with dialysis for 7.8 years, with the mean follow-up after
      transplantation of 7.3 years. The most frequent diagnoses of end-stage renal
      disease were chronic glomerulonephritis, reflux nephropathy, tubulointerstitial
      nephritis, renal hypoplasia/aplasia, and polycystic renal disease. Good graft
      function (creatinine 200 micromol/L) was recorded in 59.5% of patients. One-year,
      5-year and 10-year graft survival was 93%, 64% and 39%, and 1-year, 5-year and 10
      year patient survival after transplantation was 98%, 72% and 42%, respectively.
      Normal values of liver chemistry (AST, ALT) were found in 59.5% and elevated
      values in 40.5% of patients. Episodes of acute rejection occurred in 56% of
      patients. Proteinuria was recorded in 27%, diabetes mellitus in 18% and elevated
      blood pressure in 66% of patients. Patients with chronic C/B virus hepatitis
      having undergone renal transplantation had worse graft function and worse graft
      and patient survival than patients without chronic hepatitis. The most common
      causes of death were cardiovascular diseases, cerebrovascular diseases and
      cirrhosis hepatitis.

PMID- 22359904
TI  - [The history of kidney transplantation at Susak hospital].
AB  - Kidney transplantation is the most efficient method of renal replacement therapy.
      Development of kidney transplantation occurred in the second part of the 20th
      century. At Susak hospital, the first experimental surgical acts on animal models
      started in 1996. The first kidney transplantation from living related donor at
      Susak hospital was performed on January 31, 1971. One year later, first
      transplantation from cadaveric donor was performed. In the last 40 years,
      development of transplantation medicine in Rijeka and Croatia was successful and
      Rijeka has become one of the top transplantation centers in Croatia today. Since
      2007, Department of Urology has become Referral Center for Kidney Transplantation
      of the Croatian Ministry of Health and Social Welfare.

PMID- 22359905
TI  - [Post-transplant erythrocytosis].
AB  - Post-transplant erythrocytosis is defined as an increase in hematocrit above 55%.
      It occurs in 10%-15% of renal transplant recipients, most commonly from 8 to 24
      months after transplantation. Twenty-five percent of patients experience
      spontaneous remission within 2 years, while 75% develop symptoms and signs of
      hyperviscosity (headache, hypertension, plethora). The etiology is multifactorial
      and includes erythropoietin, renin-angiotensin system (RAS) and IGF-1 as the main
      factors. RAS inhibition with either ACE inhibitors or angiotensin receptor
      blockers is efficient therapy which decreases hematocrit in 90% of patients
      within 2 to 6 weeks, thus decreasing the incidence of fatal complications (like
      pulmonary embolism and stroke).

PMID- 22359906
TI  - [Disorders of hemostasis in chronic renal failure and renal transplantation].
AB  - The presence of end-stage renal disease (ESRD) has been associated with profound
      clinical effects on hemostasis ranging from thrombosis to bleeding complications.
      The pathogenesis of uremic bleeding is multifactorial. It has been attributed to
      platelet dysfunction, the most important feature, particularly platelet-platelet
      and platelet-vessel wall interactions. Renal replacement therapy has helped
      reduce bleeding episodes, but the risk of morbidity and mortality due to
      hemorrhage persists. Abnormalities of blood coagulation and fibrinolysis
      predispose uremic patients to hypercoagulable state carrying the risk of
      atherosclerotic cardiovascular disease and thrombotic complications such as
      thrombosis of the vascular access wall. There are differences in the measurement
      of various hemostatic parameters in patients with ESRD concerning treatment with
      either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).
      Hemostatic disturbances are overlapped by changes in the coagulation/fibrinolytic
      system after renal transplantation (RT). Despite the etiology, renal transplant
      patients are at an increased risk of thromboembolic events as a consequence of
      prothrombotic clotting and fibrinolytic abnormalities. This hypercoagulable state
      is to a large extent associated with immunosuppressive drugs. This review will
      give a summary of views on hemostasis in patients with ESRD and after RT.

PMID- 22359907
TI  - [Chronic liver diseases in patients with chronic kidney disease].
AB  - The morphological and functional integrity of the liver is vital to human health
      in general as well as to patients with renal disease. Any chronic liver disease
      will eventually lead to liver insufficiency. Liver enzymes are routinely measured
      to assess liver function in patients with or without renal failure. The use of
      standard reference values of aminotransferases to help detect liver disease is
      less useful in patients on chronic dialysis therapy. Some investigators have
      suggested that, to increase the sensitivity of liver function tests among
      dialysis patients, lower "normal" values of aminotransferases should be adopted.
      Liver biopsy may be helpful for assessing the activity and severity of liver
      disease, especially in chronic viral liver diseases. The most widely used scores
      are Ishak (6-point scale) and METAVIR (4-point scale). The most important chronic
      liver diseases associated with chronic renal disease are hepatitis B and C.
      Several types of renal disease have been recognized: mixed cryoglobulinemia,
      membranoproliferative glomerulonephritis, membranous nephropathy and
      polyarteritis nodosa. In any patient first ever diagnosed with any of the
      mentioned features, serologic and molecular tests for hepatitis B and/or C should
      be done. There is limited information on the treatment of HBV-associated renal
      diseases. Nonrandomized studies suggest that antiviral therapy may be beneficial
      in patients with glomerular disease or vasculitis due to HBV. According to
      Croatian National Guidelines for Hepatitis B and C, treatment with antiviral drug
      is recommended for patients with chronic renal disease, especially those on the
      waiting list for kidney transplantation. Decision on the type and duration of
      treatment is based on the level of viremia and biochemical and histological
      activity of liver disease. Several antiviral drugs are currently used for
      hepatitis B: pegylated interferon alpha-2a and nucleot(z)id analogues. The choice
      of analogues is based on their genetic barrier and resistance. The probability to
      develop resistance is much higher in prolonged treatment, more than 1 year. To
      avoid it, regular check-ups are mandatory. First check-up is recommended after 12
      weeks of treatment to detect the possible primary resistance to treatment.
      Similar approach is used in patients with hepatitis C. Today's standard of care
      is treatment with a combination of pegylated interferon alpha and ribavirin.
      Serum concentration of both drugs rises in patients with impaired renal function.
      The dosage should be corrected according to the glomerular filtration rate.
      Treatment with pegylated interferon alpha is not recommended in patients with
      glomerular filtration rate less than 15 mL/min and ribavirin less than 50 mL/min.
      Recent evidence suggest that nonalcoholic fatty liver disease is associated with
      an increased prevalence and incidence of chronic renal disease. Current treatment
      recommendations for nonalcoholic fatty liver disease are limited to weight
      reduction and treatment of any component of the metabolic syndrome. Liver
      cirrhosis is the terminal stage of any chronic liver disease. Mortality differs
      according to the stage of cirrhosis evaluated with Child-Turcotte-Pugh score. The
      worst prognosis have patients with grade C cirrhosis, which should be borne in
      mind when evaluating patients with terminal renal disease for treatment with
      kidney transplantation.

PMID- 22359908
TI  - [Association between viral infections and post-transplant malignancies in renal
      transplant recipients].
AB  - Immunosuppressive treatment is associated with an increased incidence of
      different malignant diseases. The etiology of posttransplant malignancies is
      multifactorial and includes decreased immune response to different viral
      infections, inappropriate removal of damaged cells, and impaired ability to
      repair DNA. EBV, HHV-8, Merkel cell virus, hepatitis B virus, hepatitis C virus
      and BK virus are all considered to be involved in the etiology of post-transplant
      malignancies. CMV has been considered as a potential causative factor in the
      development of colon cancer. However, current knowledge is mainly based on case
      reports. Further studies are needed to establish the causative role of different
      viruses in the etiology and pathogenesis of different malignant diseases in renal
      transplant population.

PMID- 22359909
TI  - [Novel immunosuppressive drugs in renal transplantation].
AB  - The major targets of novel immunosuppressive protocols are decreased toxicity and
      improved graft and patient survival. Over the last decade, several drugs have
      been demonstrated to have potential beneficial effect in transplantation. Most of
      these agents are currently in phase II or III of clinical studies.

PMID- 22359910
TI  - [Malignant disease in potential renal transplant recipients--diagnostic and
      therapeutic chalenge].
AB  - Renal transplantation is the treatment of choice for many patients with end-stage
      renal disease. There are a few generally accepted contraindications to
      transplantation: active infection, malignancy, substance abuse or non-adherence
      to therapy, chronic illness with life expectancy of less than one year, and
      poorly controlled psychosis. Potential renal transplant candidates must undergo
      thorough screening for exclusion of malignant diseases, with an individual
      approach to each patient. Patients with a history of malignancy might be placed
      on the waiting list for renal transplantation after a waiting period, which
      depends on the type of tumor and individual patient characteristics, and there
      are no signs of tumor. This group of patients require careful surveillance during
      the waiting time, as well as after transplantation.

PMID- 22359911
TI  - [Evolution of arteriovenous fistula between renal artery and vein in renal
      allograft after percutaneous nephrostomy in a renal transplant recipient].
AB  - Percutaneous urologic intervention has been accepted as a standard method to
      identify the etiology of graft dysfunction, or for treatment of urinary
      obstruction. Although ultrasound-guided procedure is a relatively safe method,
      arteriovenous fistula (AVF) is an important complication that is sometimes
      encountered. In this report, we present a renal transplant patient in whom an AVF
      and renal vein pseudoaneurysm after percutaneous nephrostomy were diagnosed.
      Surgical approach was not indicated for preservation of renal function. A 50-year
      old man was admitted with obstructive uropathy 11 months after cadaveric renal
      transplantation. Percutaneous nephrostomy was performed under ultrasound
      guidance. Doppler sonography and angiography revealed an AVF between the main
      renal artery for lower pole of the graft and renal vein, with formation of a
      venous pseudoaneurysm. Careful monitoring during the next 7 years after
      iatrogenic AVF and venous pseudoaneurysm formation resulted in preservation of
      renal graft function and improvement of the patient's quality of life.
      Radiological interventional procedure with vascular graft-stent placement was
      indicated because of rapid pseudoaneurysm enlargement and high risk of its
      rupture. Interventional endovascular graft-stent placement is a safe procedure
      for exclusion of renal allograft and AVF from circulation without indication for
      open surgery in high-risk transplanted patients. According to our opinion,
      radiological interventional or surgical procedure in transplanted patients with
      AVF and pseudoaneurysm should be considered as the treatment of choice only in
      patients who have clinical symptoms or rapid growth of AVF with a high risk of
      pseudoaneurysm rupture.

PMID- 22359913
TI  - [Yes, for life!].

PMID- 22359912
TI  - [Anderson-Fabry disease and renal transplantation].
AB  - Anderson-Fabry disease is a rare disease associated with progressive accumulation
      of globotriaosylceramide in visceral organs and vascular endothelium. The disease
      primarily affects male patients. It has long been considered that females are
      asymptomatic carriers of Anderson-Fabry disease. However, recent results
      demonstrated a significant proportion of symptomatic affected females. We present
      our experience in the treatment of patients with Anderson-Fabry disease having
      received allograft from deceased donor, as well as follow-up of patients having
      received allograft from donor with unrecognized Anderson-Fabry disease.

PMID- 22359914
TI  - [Explantation-transplantation program at Zagreb University Hospital Center--how
      to increase the number of organ donors?].

PMID- 22359915
TI  - [Study of proteomic profile of Danio rerio embryos using one-dimensional
      electrophoresis and mass spectrometry].
AB  - In the present study, a proteomic technology combining one-dimensional gel
      electrophoresis (1DE) with subsequent mass spectrometry (MALDI-TOF-PMF) has been
      successfully applied for revelation of changes in the protein profile of
      zebrafish (Danio rerio) 52 hpf embryos. Prior to 1DE separation of zebrafish
      embryonic proteins, the procedure for obtaining embryos homogenate was optimized
      by ultrasonic treatment. A total of 84 proteins, including 15 vitellogenins, were
      identified. It was shown that growing ofzebrafish embryos in the medium with
      doxorubicin (DOX) stimulated Caspase-3 induction and promoted the disappearance
      of cardiac troponins, both these findings being consistent with literature data
      on doxorubicin-induced cardiotoxicity. The 1DE-based proteomic mapping approach
      proposed herein enabled not only to identify proteins but also to register those
      changes in embryos' proteomic profile that were caused by doxorubicin.

PMID- 22359916
TI  - [Changes in fatty acid composition in the brain and liver in aging mice of high
      cancer risk AKR strain and effect of savory essential oil administration on
      leukemic process].
AB  - Age-related alterations of fatty acid composition in liver and brain of AKR mice
      was investigated. The effect of savory essential oil (Satureja hortensis L.),
      added with drinking water on fatty acid composition in these organs and the
      processes of lipid peroxidation in erythrocytes were estimated. It was found that
      during aging the percentage of saturated fatty acids and polyunsaturated fatty
      acids decreased while monounsaturated fatty acids increased. The development of
      leukemia was accompanied by the increase of saturated and polyunsaturated fatty
      acids percentage and a decrease of monounsaturated fatty acids amount. In the
      liver aging caused the increase in the percentage of saturated fatty acids, the
      decrease of monounsaturated fatty acids, while the amount of polyunsaturated
      fatty acids was not changed. Leukemia (after 8 month) was accompanied by the
      increase of percentage of monounsaturated fatty acids and the decrease in the
      amount of oleinic and docosohexaenic acids. The intake of savory essential oil
      was accompanied by intensification of polyunsaturated fatty acids synthesis in
      mice liver and reduction of lipid peroxidation products content.

PMID- 22359917
TI  - [Comparative characteristics of glucose metabolism in the liver of rats under
      acute alcohol and morphine intoxication].
AB  - The comparative analysis effect of acute alcohol and morphine intoxications on
      rats on hepatic glycolysis and pentose phosphate pathway was done. The dose
      dependent inhibitory effect of ethanol on activity of limiting enzymes of these
      metabolic ways, as well as anaerobic reorientation of glucose metabolism was
      recognised with the increase of the dose of the intake alcohol. Morfine (10
      mg/kg) activated enymes of glycolysis and pentose phosphate pathway, but in
      contrast to ethanol it did not influence these parameters at the dose 20 or 40
      mg/kg.

PMID- 22359918
TI  - [Do electrostatic interactions determine glycation of hyaluronidase derivatives
      with N-acethylhexosamines?].
AB  - Glycation of native hyaluronidase and its chondroitin sulfate modified form was
      studied with N-acethylglucosamine, N-acethylgalactosamine and their mixture, as
      well as hyaluronan fragments (n = 0-4) and their mixture. The modified form of
      hyaluronidase exhibited higher inactivation than native enzyme. The chondroitin
      sulfate modification of hyaluronidase altered its surface electrostatic
      potential, but this effect was not crucial for inactivation of hyaluronidase
      derivatives. The observed picture of the glycation action on hyaluronidase
      derivatives was opposite for glycation with mono- and di-saccharides. Such
      results give us the informative enzyme test for in vivo system in order to
      determine the dominant type of glycation agents in bloodstream and its origin.

PMID- 22359919
TI  - [Effect of water on silica gel adsorption of blood plasma components].
AB  - In this work, the study of properties of silica gel as an adsorbent for
      plasmasorption has been performed. Investigations have been realized of the
      effect of silica gel preliminary treatment conditions and a period of plasma with
      silica gel contact on plasmasorption characteristics of human blood plasma
      components, such as protein, triglycerides, cholesterol (high-density and low
      density one). The results obtained can be used for variation of silica gel
      adsorption properties, in situ at the adsorbent preparation process. For
      explanation of the experimental concentration and kinetic (temporal)
      characteristics of plasmasorption, the model of silica gel grains charging at the
      hydration was used.

PMID- 22359920
TI  - [Disfunction of membrane-receptor system of blood cells in children with diabetes
      mellitus of type I and II].
AB  - When metabolic failure in children and adolescents with diabetes, are violations
      of the structural and functional properties of membrane - the receptor apparatus
      of cells, accompanied by a decrease in ATP levels, inhibition of activity of
      membrane-bound enzyme Na+, K(+)-ATPase, a sharp decrease in insulin binding
      receptor activity and decrease glucose uptake by cells that indicates a decline
      in cell sensitivity to insulin. Diabetes in children and adolescents occurs with
      lipid disorders, activation of the processes of lipid peroxidation, manifested
      increasing concentrations of both primary and secondary products of lipid
      peroxidation, changes in structural and functional properties of erythrocyte
      membranes, as well as disturbances in the antioxidant defense system. Changes in
      the studied indexes depend on the type of diabetes and duration of the disease.
      Imbalance in the system LPO-AOD in the background shows the development of
      dyslipidemia, oxidative stress, particularly pronounced in type 2 diabetes.

PMID- 22359921
TI  - [Phenotype characteristics of humoral immunity parameters in patients with
      chronic generalized periodontitis with different blood groups].
AB  - Interrelationships between parameters of humoral immunity with AB0 blood groups
      have been investigated. The highest content of IgA to transglutaminase was found
      in A(II) patients, while the lowest content was found in AB(IV) patients. The
      blood content on anti-gliadin IgA was higher in healthy donors. The oral liquid
      of periodontic patients contained anti-gliadin IgA and IgB lacking in healthy
      donors. It have been found that 47% of healthy people and 52.7% of patients are
      infcted with Helicobacter pylori. In the group of periodontic patients A(II)
      individually predominated; they were characterized by the presence of antibodies
      to H. pylori in the oral liquid, these antibodies were absent in healthy donors.
      The pepsinogen level was higher in blood of periodontic patients than in healthy
      donors. B(III) patients had the lowest level of blood pepsinogen.

PMID- 22359922
TI  - [Blood serum phospholipids in patients with tonsillitis under combinated alcohol
      bacterial influence].
AB  - Blood serum phospholipids were investigated in alcohol abusing patients with
      tonsillitis. Most significant changes in phospholipids spectrum (low relative
      content of lysophospholipids and higher phosphatidylholine and
      phosphatidyletanolamin) in alcohol abusing patients with tonsillitis were
      observed, compared with alcohol abusers. This may be attributed to the prevailing
      influence of bacterial infection.

PMID- 22359923
TI  - [State of antioxidant system in patients with multiple sclerosis during therapy].
AB  - Activity of erytrocyte glutationperoxidase (GP), glutationreductase (GR),
      glutationtransferase (GT), glucose-6-phosphatdehydrogenase (G6PDH), catalase and
      superoxiddysmutase (SOD), and also, the level of malonic dialdehyde (MDA) and
      total antioxidant activity of blood serum were studied in patients with different
      types of multiple sclerosis. Investigation of peripherical blood was carried out
      on first day of treatment and after standard therapy of copaxone. All MS patients
      had high level of MDA and activity of GP in erythrocytes in comparison with a
      control group. Other antioxidant enzymes of erythrocytes and total antioxidant
      activity of blood serum exhibited weak positive dynamics in patients with a
      relapsing remittance of multiple sclerosis (RRMS). Decrease of activity of
      antioxidant system in patients with secondary progression multiple sclerosis
      (SPMS) was more pronounced and remained unchanged after the treatment. This is
      consistent with the more severe clinical course of thise disease.

PMID- 22359924
TI  - [The increase of bioavailability and anti-inflammatory effect of indomethacin
      loaded into phospholipid nanoparticles].
AB  - The ultrafine formulation on the base of plant phosphatidylcholine and
      antiinflammatory remedy indomethacin with nanoparticles less than 50 nm was
      obtained. Drug bioavailability after its peroral administration to rats was more
      than 2 fold higher as compared with free indomethacin. Increased antiinflammatory
      activity of indomethacin in phospholipids nanoparticles as compared with its free
      form was shown in two models of inflammation - adjuvant arthritis in rats and
      conconavalin A induced edema in mice. The increased bioavailability of
      indomethacin after administration of its phospholipid formulation allows to
      decrease a dose for achievement of therapeutic effect, that reduces risks of
      occurrence of collateral displays.

PMID- 22359926
TI  - [From molecules and genes to functional systems].
AB  - The advantages of system approach in understanding of functions of the whole
      organism are polemically substantiated. Modem analytical investigations in the
      field of molecular-cellular biology are critically viewed. It is shown that the
      results of analytical researches should be considered as components of different
      functional systems of the organism.

PMID- 22359925
TI  - [The diagnostic value of RNA oncomarkers in evaluation of malignant breast
      tumors].
AB  - The levels of the RNA oncomarkers, telomerase (hTERT), cytokeratin-19 (CK-19) and
      mammaglobin (MAM) have been investigated in capillary blood of female patients
      with mammary ductal carcinoma. The study revealed overexpression of all three
      factors in patients with this pathology. This overexpression was not found in
      healthy donors and female patients with mammary fibroadenoma. Levels of the RNA
      oncomarkers return to the normal level within 10 days after successful tumor
      resection. These results have been used for the development of diagnostic kits,
      which may be applicable for differential diagnostics, screening and postoperation
      monitoring of patients with malignant breast tumors

PMID- 22359927
TI  - [Role of genetic peculiarities in resistance of the body to detrimental impacts
      and protective effects of adaptation].
AB  - Review summarizes results of studies performed in two rat strains, August and
      Wistar, on the role of genetically determined peculiarities of the stress system
      (system managing the stress response to detrimental impacts) and of stress
      limiting systems (systems restricting activation of the stress system and,
      therefore, detrimental effects of the stress reaction) in the mechanism of
      resistance to detrimental factors and the effectiveness of adaptation defence
      against these factors. A concept is substantiated on the dependence of resistance
      to stress impacts and factors possessing a distinct stress component (emotions,
      detrimental impacts, myocardial infarction, etc.) on genetically predetermined,
      innate peculiarities of stress-limiting systems. This concept also implies a
      dependence of protective effects of adaptation to environmental factors on
      genetically determined changes in activities of stress-limiting systems during
      adaptation. Higher activity of these systems (August rats) is associated with
      higher resistance to detrimental factors whereas lower innate activity of these
      systems (Wistar rats) is associated with lower resistance. In the process of
      adaptation to environmental factors, the resistance decreases in rats with higher
      innate resistance (August rats); in animals with lower resistance (Wistar rats),
      adaptation effectively increases resistance to damages. The key factor is changes
      in activities of stress-limiting systems during development of adaptation. In
      rats with higher innate activity of these systems (August rats), adaptation
      reduces ("wearing out") of this activity in combination with declining resistance
      to damage in adapted rats. In rats with lower innate resistance of stress
      limiting systems (Wistar rats), adaptation increases both the activity of these
      systems and the resistance to detrimental factors.

PMID- 22359928
TI  - [Pathogenesis of adhesions formation after intraabdominal operations].
AB  - The article describes the pathogenesis of adhesions formation after
      intraabdominal operations. Described predisposing factors leading of which is
      mechanical trauma, resulting from the use of surgical instruments, rough
      manipulations during surgery, damage to the mesothelium by dry gauze etc, which
      cause the adhesions. The pathogenesis of adhesions formation after intraabdominal
      surgery is presented in outline form, which described the changes occurring in
      the body starting with combination of predisposing factors and ending with the
      development of adhesions with blood vessels by 7-12 days after surgery. At the
      genetic level predisposition to adhesions formation and development of adhesive
      disease is treated as a manifestation of rapid acetylation phenotype, in which
      the intensity of fibrin formation exceeds normal rate of its catabolism. Thus,
      according to modem concepts, adhesive disease is a separate nosologic unit that
      dictates the necessity of its detailed study, development and introduction new
      universal methods of preventing the adhesions formation after intraabdominal
      operations.

PMID- 22359929
TI  - [The pathogenesis factors of intraoperative hemolysis in cardiac surgery].
AB  - As shown in various studies, hemolysis is revealed in all extracorporeal circuits
      showing the increasing levels of plasma-free hemoglobin (PfHb) during and after
      cardiopulmonary bypass (CPB). The pathogenesis factors and mechanisms of
      intraoperative hemolysis are observed in this article. The role of mechanical
      blood trauma, oxygen free radical generation, activation of complement,
      preoperative defects erythrocytes, infusion preparations and other medicaments in
      postperfusion hemolysis are discussed. Along with the complete red blood cell
      (RBC) destruction (hemolysis), RBCs can also be damaged on a sublethal level,
      resulting in altered rheological properties, decreased microcirculation and organ
      dysfunction caused by hypoxia. The severity of the consequences of RBC damage,
      the high incidence of this complication and the lack of interventional strategies
      in cases of suspected or confirmed RBC damage are considered, there may be a need
      for a treatment algorithm for this phenomenon.

PMID- 22359930
TI  - [Proteomic analysis of the hematopoietic stem cell niche: focus on osteoblasts].
AB  - Methods of proteomics were used to show the influence of parathyroid hormone
      (PTH, fragment 1-34) on osteoblasts as a major component of the hematopoietic
      stem cell niche. It was found that a number of proteins are changing in response
      to PTH treatment for 4, 8 and 32 hours. The experimental work-flow has been
      optimised for the systematic identification of protein level changes upon
      cellular exposure to different environments.

PMID- 22359931
TI  - [Pathological changes in heart activity of mdx mice and future prospects of mdx
      model in cardioimmunulogy].
AB  - Dystrophin is a protein linking the cytoskeleton to a complex of transmembrane
      proteins that interact with the extracellular matrix. The fragility of the
      cardiomyocyte cell membrane resulting from the lack of dystrophin is thought to
      cause an excessive susceptibility to mechanical stress. Based on surface ECC we
      demonstrate the differences of cardiac phenotype in young (2- to 3-mo-old) and
      aged (over 1,5 years) dystrophin-deficient mdx mouse and normal mouse with the
      same genetic background. It was shown that main alterations in the mdx
      electrocardiogram concern primarily ventricular conduction velocity (QRS complex
      duration) and time of ventricular repolarization (QT interval) duration).The
      issue under discussion is whether dystrophin deficient mdx model can be used in
      research studies in cardioimmunology.

PMID- 22359932
TI  - [The role of innate immunity system in the course of adenomyosis].
AB  - The investigation of leukocytic elastase (LE) and alpha1-proteinase inhibitor
      (alpha1-PI) from patients with different stage adenomyosis and in control group
      was found activation innate immunity system in all the patients with adenomyosis.
      The degree of LE activity is a prevalence rate of adenomyosis. The degree of
      alpha1-PI activity is correlated with antiproteolytic potential that blocks the
      effects shown by LE. It can lead the prognose of disease and timely treatment.

PMID- 22359933
TI  - [Endotoxinemia and systemic inflammation in pathogenesis of chronic heart
      failure].
AB  - Large intestine microbiocenosis, levels of endotoxinemia, tumor necrosis factor
      alpha, C-reactive protein, sE-selectin, matrix metalloproteinase-9 (MMP) and
      tissue inhibitor of metalloproteinases-4 (TIMP) in chronic heart failure (CHF)
      patients was studied. Association of dysbiosis and endotoxinemia levels increase,
      systemic inflammation activation and an imbalance of MMP-TIMP system with
      progression of CHF has been shown. It can be a reason of a myocardium
      extracellular matrix structure disturbance and heart remodeling at CHF.

PMID- 22359934
TI  - [Investigation of the role of Zn2+ and zinc-containing proteins in the
      pathogenesis of bone inflammmation (the case of periodontitis)].
AB  - The levels of Ag, Al, Bi, Co, Cr, Fe, Mo, Si in osseous tissue of periodontium of
      domestic cats decreased in case of periodontitis in comparision with those of a
      healthy animals. At the same time the level of Zn increased dramatically. The
      level of tagged [14C] glycine in protein of bones of periodontium increased
      twofold and [35S] methionine 1,54 times which is explained by the fact of
      predominance of I type collagen in which one third of amino acids is represented
      by glycine while sulfur-containing amino acids are virtually absent. The latter
      are contained in non-collagenous proteins of bones of periodontium contributing
      for its metabolism. The difference in tagged aminoacids inclusion in bones of
      periodontium is mainly provoked by redistribution of the collagen and non
      collagenous proteins.

PMID- 22359935
TI  - [Analgesic effects of cannabinoids on central pain syndrome].
AB  - It was shown that cannabinoids anandamide, HU210 and WIN 55,212-2 inhibit both
      spontaneous episodes of pain and mechanical allodynia in rats with central pain
      syndrome caused by disturbance of inhibitory processes in the dorsal horns of
      lumbar spinal cord. The analgesic effect is most pronounced in the intrathecal
      route of administration. The intensity of analgesic actions of cannabinoids on
      the central pain syndrome in rats, depending on the drug is as follows: HU210 >
      WIN 55,212-2 > anandamide.

PMID- 22359936
TI  - [Cold pathology and experimental therapy of deep hypothermia].
AB  - A complete cold paralysis of respiration and thermoregulation occurs in rats at
      the temperature in the brain 16.6 +/- 0.3 and in the rectum 15.2 +/- 0.3 degrees
      C. Under the conditions of room temperature 18-19 degrees C, the respiration
      never restores, and the animals die. This is believed [6] to be the result of
      calcium ion Ca2+ accumulation in the cells of respiration and thermoregulation
      centers. After the arrest of respiration the animals were injected with the
      solution of disodium salt of ethylenediaminetetraacetic acid (Na2EDTA), which
      binds calcium ions in the blood and facilitates their removal from the cell
      (explanations in the text). In 7-9 min after the injection the calcium content in
      the blood decreased and the respiration began to restore at the temperature of
      the cold paralysis. Thermoregulation was also restored. All the test animals
      survived. All the control animals, which were not injected with Na2EDTA, died.

PMID- 22359937
TI  - [Features of the cerebral and ocular blood flow in patients with different
      clinical course of myopia].
AB  - A total of 3 groups of patients aged 16-32 years: 1st-30 patients (60 eyes)--with
      a stationary myopia of 6.5 to 9.0 D and normal intraocular pressure (IOP); 2nd-23
      patients (46 eyes)--with a high degree of progressive myopia and glaucoma with
      normalized intraocular pressure during instillation azopta included 2 subgroups:
      subgroup A--14 patients (28 eyes) - with ischemic variant of glaucoma; subgroup B
      -9 patients (18 eyes)--with dyscirculatory variant of glaucoma; 3rd group
      (control)--10 somatically healthy individuals of similar age. Results of color
      Doppler mapping of the main arteries of the brain and the eyeball revealed
      features: the predominance of the ability of middle cerebral arteries to
      vasoconstriction combined with reduced blood flow in central retinal artery and
      short posterior ciliary arteries and cause ischemica variant of glaucoma, slowing
      blood flow in the vertebrobasilar basin combined with a reduction of venous
      outflow of the of the eyeball and is accompanied by the development of glaucoma
      in dyscirculatory variant in patients with myopia of high degree.

PMID- 22359938
TI  - [Role of heat shock proteins in the mechanism of cardioprotective effect of
      transient hyperthermia and delayed preconditioning].
AB  - This review article focuses on discussing the role of the heat shock proteins
      (HSP) in myocardial protection against ischemia-reperfusion injury. In the
      present time, it has also been recognized that HSP may responsible for the
      increase in cardiac tolerance to ischemia-reperfusion after heat shock or after
      delayed ischemic preconditioning. The enhancement of the HSP expression in
      transgenic mice promotes an elevation of cardiac resistance to ischemia
      reperfusion. The same effect is induced by transfection of the HSP genes. It has
      been established that deletion of the HSP70.1 and HSP70.3 genes abolishes a
      cardioprotective effect of delayed preconditioning. The mechanism by which HSP
      protect the heart against ischemia-reperfusion remains obscure. It has been
      proposed that HSP protect the heart via refolding proteins, an increase in 5'
      nucleotidase activity, an improvement of Ca(2+)-pump function in sarcoplasmic
      reticulum during ischemia-reperfusion.

PMID- 22359939
TI  - [Stem cells technologies in the treatment of burns].
AB  - Effective treatment of bums is one of effective in present medicine. Using
      cellular technology is one of the perspective directions for restoration of the
      integrity of the skin after burn injury an overview of the commercial
      preparations, presented at the European and American markets, and technologies
      developed by leading institutions in Russia.

PMID- 22359940
TI  - [A new method of quantitative estimation of mutant allele in mitochondrial
      genome].
AB  - A new original method of quantitative estimation of heteroplasmy levels in
      mitochondrial genome is necessary for determination cut-of values mutant allele
      in tissues, associated with the emergence and development of pathologies in human
      organism. This method is based on pyrosequencing of short DNA fragments. It is
      characterized by high accuracy and good reproducibility and helps to find out
      crucial differences in the level of heteroplasmy of mitochondrial genome in
      various organs and tissue fragments from the same individual.

PMID- 22359941
TI  - [Development of current smallpox vaccines].
AB  - The review gives data on the history of smallpox vaccination and shows the high
      topicality of designing the current safe vaccines against orthopoxviruses. Four
      generations of live smallpox, protein subunit, and DNA vaccines are considered.
      Analysis of the data published leads to the conclusion that it is promising to
      use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass
      primary immunization with possible further revaccination with classical live
      vaccine.

PMID- 22359943
TI  - [Comparative study of the differential susceptibility of different cell lines to
      pandemic H1N1v influenza viruses and avian influenza, swine influenza, and human
      influenza viruses].
AB  - The proliferation characteristics of influenza viruses of different origin were
      tested in various human and animal cell cultures. Pandemic H1N1v influenza and
      swine influenza viruses were shown to have a low infectious activity in virtually
      all the test lines. In spite of this, the replication of this group of viruses
      may be detected by de novo NP synthesis. These viruses are able to activate
      programmed cell death. Moreover, a low inoculative virus dose exerts a
      stimulating effect on cell proliferation in both suspension and monolayer cell
      lines.

PMID- 22359942
TI  - [The generation and characteristics of reassortant influenza A virus with H5
      hemagglutinin and other genes from the apathogenic virus H6N2].
AB  - The experimental reassortant vaccine strain VN-gull (H5N2) containing H5
      hemagglutinin (HA) with a removed polybasic site in the connecting peptide and
      other genes from the apathogenic H6N2 virus A/gull/Moscow/3100/2006 (gull/M) was
      obtained using a two-step protocol. At Step 1, the reassortant with HA of
      A/Vietnam/1203/04-PR8/ CDC-RG and other genes from cold-adapted A/Leningrad/17/47
      (VN-Len) viruses was generated due to selection with antibody to H2N2 at 26
      degrees C. At Step 2, the reassortant VN-gull was obtained by replacing all genes
      from Len with those from gull/M due to selection with antibody to H6N2 at 39
      degrees C. The reassortant VN-Len was apathogenic and the reassortant VN-gull was
      weakly virulent in mice. Both gave rise to specific antibodies and 4 weeks after
      single inoculation they provided complete protection against further challenge
      with highly pathogenic HSN1 virus A/chicken/Kurgan/3/05 (H5N1) (Ku-Len). The
      chickens infected with live VN-gull virus showed neither clinical symptoms, nor
      fecal virus excretion; nevertheless, they gave rise to antibodies and were
      protected from the further challenge with A/chicken/Kurgan/3/2005. The high
      yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains
      for the production of inactivated and live vaccines against H5N1 viruses.

PMID- 22359944
TI  - [Preclinical studies of live intranasal H5N1 influenza vaccine with the deleted
      HS1 gene].
AB  - The paper gives the results of evaluating the efficiency of deINS1 pandemic H5N1
      vaccine candidate VN1203delNS1 which was constructed by reverse genetics on the
      basis of influenza virus strain A/Vietnam/1203/04. The safety, immunogenicity and
      cross-protection of the vaccine strain against different H5N1 virus clades were
      demonstrated in mouse and macaque models. The results showed the possibility of
      designing a new-generation replication-deficient intranasal influenza vaccine, by
      applying an approach to deleting the NS1 pathogenicity factor, an antagonist of
      the interferon system.

PMID- 22359945
TI  - [Antiviral activity of Ingavirin on an animal model for experimental disseminated
      adenovirus infection].
AB  - Adenoviruses constitute a clinically important family of human pathogens. Due to
      their wide tissue tropism, adenoviruses are able to induce different diseases
      from moderate respiratory disorders to fatal outcomes in patients with
      immunodeficiencies. The authors present the results of a trial of the antiviral
      activity of the new drug Ingavirin [2-(imidazole-4-yl-ethanamide) pentandioic-1,5
      acid] against human adenovirus type 5 on an animal model. Ingavirin is shown to
      decrease an adenoviral infectious titer in the liver and lung of neonatal Syrian
      hamsters (by approximately 1 log10 TCID50 as compared to the control) and to
      reduce the sizes of liver inflammation foci by 2-fold. Furthermore, it also
      decreases the count of virus-infected cells detectable by morphological analysis.
      Hepatocytes from Ingavirin-treated animals appear intact unlike strongly
      vacuolized cells from the animals given placebo. The findings make it possible to
      regard Ingavirin as a promising agent of the combination therapy of human
      adenovirus disease.

PMID- 22359946
TI  - [Enhancing the immunogenicity of inactivated polio vaccines with chitosan used as
      an adjuvant].
AB  - Addition of chitosan to inactivated trivalent polio vaccine or inactivated
      preparations of attenuated poliomyelitis viruses (Sabin strains) significantly
      increases immunogenicity of these inactivated poliomyelitis virus preparations.
      High neutralizing antibody titers are detected after two immunizations of mice
      and a single immunization of rats, as well as when the antigen dose was reduced
      by 4 times. Addition of chitosan as an adjuvant significantly induces cellular
      immunity.

PMID- 22359947
TI  - [Comparative estimation of the indicators of interferon, immune, and cytokine
      states in the comprehensive study of patients with herpesvirus infections].
AB  - The paper provides the data of a comparative analysis of the indicators of immune
      and interferon states and cytokine profile and the results of virological studies
      in patients with different (acute and chronic) forms of mixed herpesvirus
      infection (with virus simplex herpes types 1 and 2, Epstein-Barr virus, human
      herpesvirus type 6, and others). Pronounced changes were found in immune
      responses in such patients. There were decreases in IFN-alpha and IFN-gamma
      values in 36 and 13%, respectively; 51% of the subjects showed a reduction in
      both IFN-alpha and IFN-gamma along with the high titers of antibodies to viruses
      of the Herpesviridae family and their infectious activity. There were changes in
      the cytokine profile, activation of IFN-alpha, IL-2, IL-8, IL-10, and IL-18 gene
      expression, and suppression of IL-2 gene transcription in the majority of the
      patients. Determination of IFN susceptibility revealed that 86% of the subjects
      responded to IFN-alpha therapy and only 11% of cases did to IFN-gamma one.

PMID- 22359948
TI  - [Molecular genetic echovirus 9 variants identified in patients with aseptic
      meningitis in Russia in 2007-2009].
AB  - In 2009 echovirus 9 caused a higher seasonal incidence of enterovirus infection
      (EVI) and its several outbreaks in a number of regions of Russia. Analysis of the
      partial VP1 coding region differentiated 4 phylogenetic lineages of echoviruses 9
      variants identified in patients with aseptic meningitis and EVI in 2007-2009. One
      variant of echovirus 9 was most commonly encountered in 2009. Echoviruses 9
      identified in different areas, which had a high (98.2-100%) homology of
      nucleotide sequences of the partial VP1 coding region, varied in the amino acid
      sequences within the B-C loop.

PMID- 22359949
TI  - [The epidemiological, epizootological, and etiological characteristics of the
      2006-2007 outbreak of hemorrhagic fever with renal syndrome in the Tambov
      Region].
AB  - The findings suggest that there are natural foci of hantavirus infection in the
      Tambov Region. There is evidence that Dobrava/Belgrade hantavirus (DOB-Aa) was a
      leading etiological agent in the outbreak of the disease in the winter of 2006
      2007. Epidemiological analysis showed that the outbreak of hemorrhagic fever with
      renal syndrome (HFRS) afflicted the region during November to April, by reaching
      its peak in January (52.2%). Among the patients with HFRS, rural dwellers were
      91%. People were infected with the virus mainly by taking care of domestic
      animals (97.2%). The reservoir of the virus and the source of its human infection
      in the outbreak was a field mouse, its western subspecies Apodemus agrarius
      agrarius, which was absolutely dominated among all the virus carriers.

PMID- 22359950
TI  - [Multipotent mesenchymal stem cells of desquamated endometrium: isolation,
      characterization and use as feeder layer for maintenance of human embryonic stem
      cell lines].
AB  - In this study, we characterize new multipotent human mesenchymal stem cell (MSC)
      lines derived from desquamated (shedding) endometrium in menstrual blood. The
      isolated endometrial MSC (eMSC) is an adhesive to plastic heterogeneous
      population composed mainly of endometrial glandular and stromal cells. The
      established cell lines meet the criteria of the International Society for
      Cellular Therapy for defining multipotent human MSC of any origin. The eMSCs have
      positive expression of CD73, CD90, CD105, CD13, CD29, CD44 markers and the
      absence of expression of the hematopoietic cell surface antigens CD19, CD34,
      CD45, CD117, CD130 and HLA-DR (class II). Multipotency of the established eMSC is
      confirmed by their ability to differentiate into other mesodermal cell types such
      as osteocytes and adipocytes. Besides, the isolated eMSC lines partially (over
      50%) express the pluripotency marker SSEA-4, but do not express Oct-4.
      Immunofluorescent analysis of the derived cells revealed the expression of the
      neural precursor markers nestin and beta-III-tubulin. This suggests a neural
      predisposition of the established eMSC. These cells are characterized by high
      rate of cell proliferation (doubling time 22-23 h) and high cloning efficiency
      (about 60%). In vitro the eMSCs undergo more than 45 population doublings
      revealing normal karyotype without karyotipic abnormalilies. We demonstrate, that
      the mititotically inactivated eMSCs are perfect feeder cells for human embryonic
      stem cell lines (hESC) C612 and C910. The eMSC being a feeder culture maintain
      the pluripotent status of the hESC, which is revealed by the expression of Oct-4,
      alkaline phosphatase and SSEA-4. When co-culturing, hESC retain their morphology,
      proliferative rate for more than 40 passages and capability for spontaneous
      differentiation into embryoid bodies comprising the three embryonic germ layers.
      Thus, an easy and non-invasive extraction of the eMSC in menstrual blood, their
      multipotency and high proliferative activity in vitro without karyotypic
      abnormalities demonstrate the potential of use of these stem cells in
      regenerative medicine. Using the derived eMSCs as the feeder culture eliminates
      the risks associated with animal cells while transferring hESC to clinical
      setting.

PMID- 22359951
TI  - [The interaction between CDX2 transcription factor and DDX5 RNA helicase].
AB  - Previously, our results of a two-hybrid screening essay allowed us to recognize
      p68 (DDX5) as a possible partner of CDX2. The recent part of research was carried
      out to confirm this interaction. We show the co-localization of these proteins in
      the nuclei of colon carcinoma cell line and of epithelium of villi. By means of
      GST-pulldown we reveal DDX5 as a part of a complex with CDX2. During the
      investigation of the effect of DDX5-CDX2 interaction upon beta-catenin-mediated
      transcription regulation we note that in each of three investigated cell lines
      Cdx2 acts as an activator of luciferase expression. In T98G and U20S cell lines
      we observe a partial decline of beta-catenin transcription enhancing effect while
      interacting with CDX2. In the cell systems studied, DDX5 acts as a weak repressor
      both solely and together with CDX2 and beta-catenin. Concerning the influence
      upon D1 cyclin promoter, we find that, depending on environment, CDX2 may either
      decline its transcription (U20S line) or raise it (T98G). Besides, PDGF reduces
      CDX2 activity both in activation and repression. When DDX5 and CDX2 are
      transfected in T98G cells together, the repressing activity of DDX5 is leveled
      with activation by Cdx2. In both cell lines the native DDX5 acts as a weak
      repressor of D1 cycline; PDGF treatment does no significant effect on its
      activity.

PMID- 22359952
TI  - [Generation of rat induced pluripotent stem cells: the analysis of reprogramming
      and culturing media].
AB  - The rat represents very important, superior in many respects to the mous, animal
      model for studying pharmacology, physiology, ageing, cardiovascular etc. However,
      numerous attempts to derive rat ES cells necessary to carry out loss-of-gene
      function studies have not been successful thus far. Therefore rat induct
      pluripotent stem cells (or riPS) should provide a notable alternative to ES cell,
      allowing to study gene functions in this valuable animal model. Here we report an
      improved lentivirus-based riPS derivation protocol that makes use of small
      inhibitors of MEK and GSK3. We show that the excision of proviruses does not
      affect neither karyotype and pluripotency state of these cells. Also, we propose
      genetic tool for an improvement of the quality of riPS cells in culture. These
      data may prompt further iPS-based gene targeting in rat as well as the
      development iPS-based gene therapies, using this animal model.

PMID- 22359953
TI  - [Genetic manipulation and studying of differentiation properties of rat induced
      pluripotent stem cells].
AB  - Induced pluripotent stem (iPS) cells are derived from somatic cells reprogrammed
      to the pluripotent state by the induced expression of defined transcription
      factors, achieved for the first time by the seminal work of Takahashi and
      Yamanaka. This new type of pluripotent cells has offered new exciting options in
      regenerative medicine allowing the replacement of cells and organs with the
      patient's own cells thereby avoiding immunological complications. In order to
      develop such technologies in approved animal models, iPS cells were also
      generated from rodents. Of course, the most important model for studying of
      different diseases is rat. In this study, we present a method suitable for rat
      iPS cells genetic modification by stable transfection and show necessary
      conditions for the first stages of direct differentiation.

PMID- 22359954
TI  - [Composite materials based on chitosan and montmorillonite: prospects for use as
      a matrix for stem and regenerative cell cultivation].
AB  - This paper examines the structural and mechanical properties of composite
      materials based on chitosan and micro- and nanoparticles of Na-montmorillonite
      and possibility of application for cultivation and targeted delivery of
      mesenchymal stem cells and regenerative cells. It's have been shown by addition
      of Na-montmorillonite biomaterial acquires stability of structural and mechanical
      properties in the sterilization process the handling of liquid media in cell
      culture. In vitro studies using dermal fibroblasts and adipose tissue mesenchymal
      stem cells demonstrated that this material has a set of properties to ensure
      matrix biocompatibility.

PMID- 22359955
TI  - [Potential role of presenilin 1 in regulation of synaptic function].
AB  - One of the earliest neuropathological symptoms of Alzheimer's disease is the loss
      of synapses, which preceed the formation of amyloidosis and neurodegeneration.
      Although most cases of early-onset familial Alzheimer's disease are caused by
      mutations in the presenilin 1 (PS1) gene, the functions of PS1 and its role in
      synaptic disfunction are not yet completely understood. In this paper we analysed
      of the intracellular and extracellular distribution of PS1 in the cultures of
      mouse cortical embryonic neurons. We found that PS1 is concentrated on the
      surface of the growth cone and at neurite contact sites. PS1 was also found in
      synapses where it is co-localized with synaptophysin. Independent evidense of
      involvement of PS1 in synaptic function we obtained by transfection of neurons
      with GFP-PS1 cDNA. GFP was colocalized with synaptophysin in transfected
      cultures. GFP-immunoprecepitates from transfected neurons contained processed N
      cadherin. This result presents an additional proof of involvment PS1 in synapse
      formation. To evaluate the role of PS1 inactivation in the synaptic functions, we
      compare synaptic density in neuronal cell cultures from PS1 knockout mice PS1 (-/
      ) and wild type mice PS1 (+/+). Our results clearly show that PS1 (-/-) displayed
      a low number of morphological synapses in comparing with wild type culture PS1
      (+/+). In summary, our results indicate a role of PS1 in synaptic function.

PMID- 22359956
TI  - [Ultrastructure of coronary microvessels in conditions of heart reperfusion
      following prolonged ischemia while applying various methods of artificial
      hypothermia].
AB  - It has been found out that in children with Roger's disease corrected in the
      conditions of two fundamentally different procedures of anesthetic management,
      myocardial reperfusion after cardiac arrest under artificial hypothermic
      circulation is accompanied by obstruction of more than 30% of coronary bed
      microvessels with hydropic endothelial cells or their cystiform fragments. The
      content of necrotic cells increases, while the "working" cells demonstrate a
      decrease in myocropinocytotic transport characteristics. Circulatory arrest under
      perfusionless hypothermia and immersion reperfusion do not result in a dramatic
      change of general morphology of microvessels as compared to the control group,
      while a heterogenic response of the structures responsible for transendothelial
      transfer of macromolecules provides the basis for recovery of the endothelium
      structure and function, as a patient's temperature reaches a standard value.

PMID- 22359957
TI  - [Effect of formaldehyde in low concentrations on the proliferation and
      organization of the cytoskeleton of cultured cells].
AB  - 3-4% (1.07-1.42 M) formaldehyde is one of the most popular and well-known organs,
      tissues and cells fixer. In this manuscript we have shown that formaldehyde in
      concentrations of up to 60 microM (0.0002%) does not have any negative effect on
      the viability of cell lines A431, HEK293 and primary rat fibroblasts, but it is
      also increases the proliferative activity of A431. The influence on A431 cells
      might be explained by the activation of epidermal growth factor receptors as a
      result of their interaction with formaldehyde.

PMID- 22359958
TI  - [Immuno- and histochemistry characteristics of morula and test cells in three
      ascidian species].
AB  - One of the hypotheses suggests that test cells play a part in a larval tunic
      formation like morula cells in adult ascidians. It was shown that the antibodies
      against morula cell proteins of 26 and 48 kDa of the ascidian Styela rustica
      react on the paraffin sections with both the granules of morula cells and test
      cells of ascidians S. rustica and Boltenia echinata. Among the test cell proteins
      of S. rustica SDS-electrophoresis revealed at least 5 major proteins but no one
      with the molecular mass of 26 and 48 kDa and none of them react with the
      antibodies. At the same time AB26 bind the proteins with similar molecular masses
      in blood cells and in the probe containing test cells--27 and 28 kDa,
      correspondingly,--of ascidian Molgula citrina. Comparative histochemical analysis
      of morula and test cells of these three ascidian species was carried out. There
      are a lot of acid polysaccharides combined with proteins in test cells whereas
      morula cells contain mainly positively charged proteins. Thus it could be
      supposed that degree of manifestation of antigens might be different in the
      conditions of immunoblot and immunohistochemical analysis. The hypothesis of the
      similarity in morula and test cells functions and their interrelationship is
      discussed.

PMID- 22359959
TI  - Berwick's push for accountable care helped the ESRD program.

PMID- 22359960
TI  - Referrals needed to impact survival.

PMID- 22359961
TI  - The QIP: will it improve dialysis care? An overview.
AB  - The Centers for Medicare & Medicaid Services End-Stage Renal Disease Quality
      Incentive Program is a pay-for-performance initiative that imposes dialysis
      payment reductions of up to 2% for suboptimal quality. In payment years 2012 and
      2013 the methodology is simple, a point system based on performance in dialysis
      adequacy and anemia. In payment year 2014 (performance period begins Jan. 1,
      2012) the QIP changes substantially, with a methodology that more closely
      resembles the Medicare Hospital Inpatient Value-Based Purchasing Program.
      Succeeding with the QIP will require both providing high quality care for a wider
      variety of measures, and a clear and complete understanding of the program
      structure and the new scoring methodology. In this review we discuss the QIP,
      with a comprehensive explanation of measures and scoring procedure.

PMID- 22359962
TI  - Tackling pay-for-performance: current and future challenges.

PMID- 22359964
TI  - Nurses in the trenches.

PMID- 22359963
TI  - Perpetuating sub-optimal care: CMS, QIPs, and the hemoglobin myth.
AB  - As the new Centers for Medicare & Medicaid Services' Quality Incentive Program
      takes effect, the implications are enormous for dialysis patients. Contrary to
      its intention, the Quality Incentive Program, with its upper hemoglobin limit,
      may well stifle innovative practice-based research and practical approaches to
      anemia management. An opportunity to move away from an excessive preoccupation
      with ESAs to substantially improve patient outcomes, and to do so at a much lower
      cost, may well be lost to patients, providers, and CMS as a result.

PMID- 22359965
TI  - A timely practice; a nurse-driven telemetry discontinuation protocol.

PMID- 22359966
TI  - Covert crime at work.

PMID- 22359967
TI  - Military sexual trauma.
AB  - Nurses' awareness of MST as a specific type of sexual assault within the military
      culture and sensitivity to the physical and psychological symptoms are important
      aspects of care. Nurses must treat the physical and emotional components of
      sexual assault in all settings; however, referral to the veterans administration
      programs and resources is key for the woman veteran to receive the specialized
      care developed by the healthcare system. Women veterans who have PTSD from MST
      and combat exposure are prone to depression, suicide and substance use/abuse.
      Nurses must not fear asking the woman if she is having suicidal thoughts or has a
      plan and intent to follow through with the plan. MST and PTSD may result in
      internalized anger, shame, self-blame, helplessness, hopelessness and
      powerlessness. Patient safety is of utmost importance. Assessing Patients for
      Sexual Violence, A Guide for Health Care Providers (2009) is a useful resource
      for nurses. The National Center for PTSD (2009) newsletter on the topic of MST
      includes a list of research studies. The work of Benedict (2007) and Corbett
      (2007) provide additional personal accounts of women soldiers who were in the
      Middle East conflicts. The nurse's referral to specialized services to treat MST
      and PTSD with evidence-based therapies is a crucial first step in the resiliency
      and well-being of these brave women who have served in all branches of the U.S.
      military.

PMID- 22359968
TI  - Your voice, your association: benefits of district participation in a
      professional association.

PMID- 22359969
TI  - Learned helplessness, hardiness, and risk-taking. Factors related to prescriptive
      practice among nurse practitioners.

PMID- 22359970
TI  - Health care costs.

PMID- 22359971
TI  - Heart of the matter.

PMID- 22359972
TI  - What's new in prenatal diagnosis in 2012?

PMID- 22359973
TI  - Asthma triggers on the Cheyenne River Indian Reservation in western South Dakota:
      the Breathing Relief Education and Tribal Health Empowerment (BREATHE) Study.
AB  - BACKGROUND: The purpose of this article is to better understand asthma triggers
      and possible causes of exacerbations among BREATHE participants on the Cheyenne
      River Indian Reservation in western South Dakota. METHODS: To qualify for
      enrollment, participants had to have physician-diagnosed asthma, be uncontrolled
      and have persistent symptoms. Participants were asked to identify their top two
      asthma triggers throughout their one-year enrollment during initial visits and
      subsequent phone follow-ups. In addition, participant's medical records were
      reviewed for visits to the emergency department (ED) to demonstrate asthma
      exacerbations. RESULTS: In 2008, 127 interviews were conducted with 45 enrolled
      participants for a total of 254 results. Overall, the three most common self
      reported triggers were cold air, dust and smoke and these comprised nearly half
      (48.4 percent) of all reports. Dust was reported in 16.5 percent of interviews
      and ranked among the top four for every season. Smoke (12.6 percent) and cold air
      (19.3 percent) were leaders in all seasons except summer, but humid air, pollens
      and strong odors were unique to summer. Exercise/activity ranked high during the
      winter and spring, but was reported less in summer and fall. There was no
      identifiable trend in ER visits by season. CONCLUSION: People with asthma living
      on the Cheyenne River Indian Reservation or other locations with similar
      community and geographic demographics are most likely to suffer an asthma
      exacerbation from exposure to cold air, dust, smoke and exercise/activity. Asthma
      education is necessary on all levels, but information on avoidance and control of
      these most common reported triggers is especially important.

PMID- 22359974
TI  - Interprofessional education: we are all in this together.

PMID- 22359975
TI  - Quality focus: quality measurement 2.0.

PMID- 22359976
TI  - DAKOTACARE update: provider quality data ... it really matters.

PMID- 22359977
TI  - Evidence-based evaluation and current practice of non-operative treatment
      strategies for lumbar stenosis.
AB  - OBJECTIVE: A number of non-operative treatment protocols have been proposed in
      the literature for lumbar stenosis. However, the available primary research
      describes inadequately the employed protocol. This causes difficulties in
      distinguishing which interventions are more effective in reducing symptoms.
      METHODS: We reviewed existing studies in order to promote the construction of an
      evidence-based strategy for non-operative treatment rehabilitation of lumbar
      stenosis patients. Randomized controlled trials describing insufficiently the non
      operative treatment rehabilitation protocols were excluded since the results may
      not direct this review towards a favorable treatment plan. RESULTS: A protocol
      has been outlined to inform the clinician and to elucidate the effectiveness of
      non-operative treatment through randomized controlled trials. The results of this
      study indicate that a comprehensive exercise and manual therapy protocol is more
      effective in reducing symptoms than a less intensive exercise program.
      CONCLUSIONS: A comprehensive non-operative treatment comprising of flexion
      exercises, manual therapy and treadmill exercises appears to be more beneficial
      in reducing symptoms than a less vigorous program comprising of flexion
      exercises, treadmill training and home exercise.

PMID- 22359978
TI  - Effect of short-term standard therapeutic regimens on neuropeptide Y and adipose
      tissue hormones in overweight insulin-resistant women with polycystic ovary
      syndrome.
AB  - AIM: The study was aimed at elucidating the influence of a 3-month treatment with
      routine therapeutic regimens--oral hormonal contraceptives (OHC) with
      antiandrogenic activity (a standard combination of ethynil estradiol 35 microg
      plus cyproterone acetate 2 mg) in combination with insulin sensitizing agents-
      metformin (Group I) and rosiglitazone (Group II) on adipose tissue hormones and
      hypothalamic neuropeptide Y (NPY) in women with polycystic ovary syndrome.
      PATIENTS AND METHODS: The study included 66 overweight insulin resistant women
      with PCOS according to the recent ESHRE-ASRM criteria randomized into 2 age
      matched therapeutic groups. RESULTS: Significant decrease of leptin (P < 0.01; P
      = 0.001, resp.), resistin (P < 0.01; P < 0.01, resp.), tumour necrosis factor
      alpha (TNF alpha) (P = 0.001; P < 0.001, resp.), and NPY (P < 0.05; P < 0.001,
      resp.) was observed in both groups after treatment. These findings were in
      parallel with a significant decrease in the anthropometric parameters of body
      weight in the metformin group only. No significant changes in hormonal
      characteristics of the groups were found except for a significant decrease in
      androstenedione and DHEA-S (P < 0.05) in the metformin group and in 17-OH
      progesterone (P < 0.05) in the rosiglitazone group. HDL-cholesterol rose and
      diastolic blood pressure fell significantly (P < 0.05) in the metformin group.
      CONCLUSION: Our data suggest beneficial effects of the treatment on potential
      cardiovascular risk in insulin resistant PCOS women.

PMID- 22359979
TI  - Adherence to bisphosphonate therapy in postmenopausal osteoporotic women.
AB  - INTRODUCTION: Osteoporosis is a metabolic bone disease caused by a decrease in
      the bone mineral density. It is a major public health threat as it weakens bones,
      especially those in the wrist, spine, or hip, and causes them to break easily.
      AIM: The study aimed to find how strictly postmenopausal women with osteoporosis
      adhere to a long-term therapy with bisphosphonates. PATIENTS AND METHODS: The
      study was conducted over a 24-month period. It included a total of 341 randomized
      patients with postmenopausal osteoporosis; the diagnosis was made on the basis of
      clinical and radiological evidence and a DXA T-score of the axial skeleton and
      the left hip less than -2.5 SD. Therapy included per os administration of
      alendonate 70 mg once a week or 50 mg of ibandronate once a month. RESULTS: The
      patient medication persistence at the end of month 12 was 86.80%, and at the end
      of month 24 month - 58.94%. The medication possession ratio (MPR) in the
      bisphosphonate therapy at 6, 12, 18, and 24 months varied from 0.93 to 1.00. This
      suggests that there was a very good patient medication adherence of the study
      subjects to the 24-month treatment with bisphosphonates. The patient medication
      persistence dropped significantly at the end of month 12. CONCLUSION: Compliance
      of patients with antiresorptive therapy depends on the specific socio-economic
      conditions and the attending physician's behaviour. Very rarely, treatment is
      discontinued because of adverse effects exerted by the drugs or because patients
      may not be convinced that they have osteoporosis.

PMID- 22359980
TI  - Immune response and immunologic memory in medical personnel vaccinated with
      hepatitis B vaccine.
AB  - The occupation-related nature of Hepatitis B viral infection in medical personnel
      has been well documented in a lot of studies. The only reliable way of prevention
      of this infection is immunisation with hepatitis B vaccine. AIM: To follow-up the
      primary immune response after immunisation with recombinant vaccine and its
      duration in adult immunocompetent subjects. MATERIALS AND METHODS: One hundred
      sixty-five health-care workers working at St. George University Hospital, Plovdiv
      in 2009/2010 were included in the study and allocated to two groups. Group 1 (N1
      = 70) was followed up for the primary immune response after immunization; group 2
      (N2 = 95) was with documented immunization in 1998/1999 (n = 81) and in 1994/1995
      (n = 14). Tests based on ELISA for quantitative determination of anti-HBs in
      mIU/ml were used. The measurement were performed at the National Reference
      Laboratory of Viral Hepatitis at the NCIPD, Sofia. Descriptive statistics, non
      parametric and parametric tests, qualitative correlation were used to analyse
      data. RESULTS: Group 1 mean age was 40.3 +/- 2.6 years; anti-HBs concentration of
      > or = 10 mIU/ ml was found in 92.8%. No association between the immune response
      and the commonly involved factors such as gender, age, overweight, smoking, etc.,
      was found. In group 2, anti-HBs concentration of > or = 10 mIU/ml was found in
      77.9%: it was in 75.3% in those immunized 10 years before, and in 92.9% in those
      immunized 15 years before (t = 0.24, p > 0.05). A booster dose of the vaccine was
      received by 15/21 subjects from group 2 (those immunized 10 years before that)
      with anti-HBs < 10 mIU/ml. After the booster, 9/15 produced anti-HBs in
      protective concentrations (anamnestic immune response). The actual level of
      seroprotection among the immunized more than 10 years ago was 92%. CONCLUSION:
      This study and the documentation of the primary postvaccinal immunity in high
      risk medical personnel will help specify if additional hepatitis B vaccine shots
      are needed.

PMID- 22359981
TI  - Fetopathological aspects of holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a congenital central nervous system malformation
      estimated to occur in 1/250 conceptuses and 1/10,000 live births. While the
      severe forms, which are incompatible with life, are easier to detect in the
      prenatal period, the milder forms can remain unrecognised. As this can have
      serious consequences for the pregnancy and malformation carriers it is of crucial
      importance to find ways of timely detection of this pathological condition. The
      present study AIMED at finding an association of holoprosencephaly with facial
      dysmorphia and anomalies of visceral organs that would alert the physician to be
      very careful in making the prenatal diagnosis, which may require termination of
      pregnancy by medical indications. MATERIAL AND METHODS: The study included 15
      fetuses diagnosed with holoprosencephaly out of 2095 cases analysed post-mortem
      in the Fetopathology Clinic at the Centre for Maternity and Neonatology in the
      town of Tunisia over a period of 3 years (Oct. 2006 - Oct. 2009). The fetuses
      were analysed macro- and microscopically. RESULTS: All forms of holoprosencephaly
      include elements of facial dysmorphism with the facial phenotypes of cyclopia,
      cebocephaly and ethmocephaly. It can be associated with specific internal organs
      anomalies, the hydrocephaly being the most common anomaly of the central nervous
      system. Our study suggested that holoprosencephaly can be correlated with
      craniofacial anomalies affecting the midfacial and medium craniovisceral
      structures. CONCLUSION: The anatomical variations of HPE and the phenotypic
      facial correlations require a systematic and targeted study of central nervous
      system.

PMID- 22359982
TI  - Biomarker profile of minor physical anomalies in schizophrenia patients.
AB  - AIM: The aim of this study was to determine the frequency and topographical
      distribution of minor physical anomalies (MPAs) in schizophrenia patients and
      control subjects, and the ability of the items of the Waldrop scale to predict
      the patient-control status. MATERIAL AND METHODS: 128 schizophrenic patients (66
      men, 62 women) and 103 normal controls (49 men, 54 women) were evaluated for MPAs
      with a modified version of the Waldrop scale. RESULTS: Compared with controls,
      schizophrenia patients showed a higher incidence of almost all studied MPAs,
      differences being statistically significant for 12 items: fine electric hair,
      abnormal hair whorls, epicanthus, adherent ear-lobes, lower edges of the ears
      extending backward/upward, malformed ears, asymmetrical ears, high/arched palate,
      furrowed tongue, smooth/rough spots on the tongue, III toe > or = II toe, big gap
      between I and II toe. Some anomalies occurred with almost equal frequency in
      schizophrenic patients and controls, while others were more than 10 times more
      common in patients (odds ratio: 0.62 - 10.55). The distribution frequency of MPAs
      in schizophrenia tended to increase in the cranial direction. Nine predictor MPA
      biomarkers successfully distinguished 81.10% of patients, 81.55% of controls, and
      81.30% of all examined subjects. CONCLUSIONS: The elevated incidence of MPA
      biomarkers in schizophrenia patients implies impaired neurodevelopment that
      increases the risk for the development of schizophrenia. The pattern of changes
      in the morphological characteristics suggests they may be a random outcome of a
      general neurodevelopmental defect or may reflect different neurodevelopmental
      defects that allow better characterization of schizophrenia patients subgroups.

PMID- 22359983
TI  - Assessment of body composition of male patients with type 2 diabetes by
      bioelectrical impedance analysis.
AB  - INTRODUCTION: Type 2 diabetes is a metabolic disorder and as such should affect
      the components of body composition of diabetics. The changes it induces in
      patients complement the anthropological characteristics of this disease. The AIM
      of the present study was to assess the effect type 2 diabetes has on some of the
      body composition components in male diabetics. MATERIAL AND METHODS: The study
      included 169 male patients with type 2 diabetes. All patients (ethnical
      Bulgarian) were allocated into two age groups: group 1--patients aged 40-60 years
      and group 2--patients aged 61-80 years. Direct measurements of parameters were
      performed with a Tanita body composition analyser. The bioimpedance parameters we
      measured were body fat percentage (%BF), total body water percentage (%TBW),
      muscle mass (MM), bone mass (BM), and visceral fat (VF). The derived parameters
      were total body fat (TBF) (kg), active body mass (ABM) (kg), active body mass
      percentage. RESULTS: Body composition of male diabetics aged 40-60 years: %BF, VF
      and TBF were statistically significantly higher in diabetics than in healthy
      controls. Body composition of male diabetic patients aged 61-80 years: BM and VF
      were significantly higher in diabetic patients than in controls. %BF and MM did
      not have a high statistical significance. Inter-age comparison of body
      composition in male diabetics: we found that %BF, %TBW, MM and BM tend to be
      higher in 40-60-year-olds. Visceral fat was increased in the 61-80-year-olds, the
      difference reaching high statistical significance. CONCLUSION: Bioimpedance
      analysis (BIA) of body composition showed the total body fat in male diabetics of
      both age groups to be greater than that in controls. TBF was greater in the
      younger age group at the expense of the subcutaneous fat, while in the more
      elderly patients it was the visceral fat that was increased, which makes their
      body composition correlate rather adversely with the prognosis, course and
      outcome of the disease. The relative percentage of active body mass was greater
      in the healthy individuals than in diabetic patients. This parameter was higher
      in the younger age group of diabetic patients than in the more elderly patients;
      this finding is probably due to the longer duration of the disease and also to
      aging changes such as osteoporosis, muscle atrophy and decreased quantities of
      body water.

PMID- 22359984
TI  - Sensitizing effect of tacrine on M-cholinergic receptors in gastric smooth muscle
      of rats.
AB  - AIM: To find if tacrine exerts a sensitizing effect on the cholinergic receptors
      of gastric smooth muscles, and study some of the mechanisms inducing it and
      measure the relative intensity of tacrine's effects on contractile activity.
      MATERIAL AND METHODS: Isometric recording of the mechanical activity of gastric
      smooth muscle preparations; determination of acetyl-cholinesterase activity in
      smooth-muscle tissue homogenates using Ellman's method. RESULTS: We found that
      the threshold concentration for tacrine not reducing the acetylcholinesterase
      activity and not having an effect on the smooth muscle preparations was 1 x 10(
      8) mol/l. This concentration, however, significantly increased the acetylcholine
      induced contraction compared with the controls, after the smooth-muscle tissue
      was incubated for 60 or 100 min. Treating smooth-muscle preparations with tacrine
      in a concentration of 5 x 10(-6) mol/l triggered a contraction induced by the
      drug's anti-cholinesterase activity. A secondary contraction was induced after
      38.6 +/- 5.6 min. There was no secondary contraction after the control
      acetylcholine-induced effect. Atropine (1 x 10(-6) mol/l) inhibits this effect.
      Preliminary treatment of smooth muscle preparations with hexamethonium (1 x 10(
      6) mol/l) did not change significantly the intensity of the first phase of
      tacrine-induced contraction and shifted in time the appearance of the second
      contractile phase. CONCLUSION: Tacrine has a sensitizing effect on M-cholinergic
      receptors; it occurs after a long incubation of the gastric smooth muscles with
      the drug and is manifested as a secondary contraction which is shifted in time
      and is significantly inhibited by atropine.

PMID- 22359985
TI  - Simultaneous thin-layer chromatography-densitometric analysis of sibutramine and
      citalopram.
AB  - Due the presence of sibutramine and citalopram in a number of drugs,
      neurotransmitter reuptake inhibitors. Sibutramine reduces the reuptake of
      serotonin, norepinephrine, and dopamine; citalopram is an antidepressant drug of
      the selective serotonin reuptake inhibitor. The thin-layer chromatography
      densitometric behavior of some centrally acting serotonin reuptake inhibitors has
      been studied. The proposed analytical method is suitable for qualitative and
      quantitative analysis of sibutramine and citalopram.

PMID- 22359987
TI  - The TMA legislative agenda--how does it happen?

PMID- 22359986
TI  - Prevalence and risk factors for low back pain in industrial workers.
AB  - OBJECTIVES: The aim of the present study was to determine the prevalence of low
      back pain (LBP) in industrial workers, check for possible LBP related risk
      factors and investigate the associations between physical activity and severity
      of low back pain. METHODS: We conducted a cross-sectional study among 430 workers
      of an industrial company over the previous 12 months. The industrial workers were
      given questionnaires and assigned to two groups: (1) with low back pain, (2)
      without low back pain. Group 1 was then divided into three subgroups according to
      the answer to question (a) LBP without irradiation, called mild cases, (b) LBP
      with irradiation above the knee, called moderate cases, LBP with the irradiation
      below the knee, called severe cases. RESULTS: LBP was found in 61.6% of workers.
      The prevalence of LBP was significantly associated with physical activity (p =
      0.03). There was a significant difference between frequent physical activity and
      severity of LBP (p = 0.01). Work-related physical factors showed strong
      associations with LBP. The main risk factors for low back pain among production
      workers were extreme trunk flexion (OR = 3.5, 95% CI 1.7-7.3), as well as lifting
      of loads (OR = 3.5, 95% CI 1.9-6.2), pushing or pulling heavy loads (OR = 3.5,
      95% CI 1.9-6.2) and exposure to whole body vibration (OR = 1.7, 95% CI 1.0 -3.0).
      CONCLUSION: Daily life conditions, job-related factors are associated with the
      occurrence of low back pain. These results suggest that individuals with LBP
      should avoid nonspecific physical activities to reduce pain and improve
      psychological health.

PMID- 22359988
TI  - "Standards of care": a second opinion.

PMID- 22359989
TI  - How do I find out my eprescribing status?

PMID- 22359990
TI  - Commissioner John Dreyzehner: emphasizing "health" over "health care".

PMID- 22359991
TI  - Health reform in 2012: what you should know.

PMID- 22359992
TI  - Choosing the right technology support for your practice.

PMID- 22359993
TI  - Carcinoma of unknown primary: check the liver... thanks to TTF-1.
AB  - Carcinoma of unknown primary (CUP) is not uncommon and poses both diagnostic and
      therapeutic challenges. Recent developments in immunohistochemical (IHS) stains
      in diagnostic pathology help resolve many of these clinical dilemmas. Antibodies
      against Thyroid Transcription Factor (TTF-1), a relatively new and organ specific
      marker that stains lung and thyroid malignancies, are commonly included in the
      first battery of stains when dealing with a CUP. The usual pattern of staining
      for TTF-1 is purely nuclear. However, it was recently noticed that TTF-1 stains
      the mitochondria of benign hepatocytes and tumor cells in hepatocellular
      carcinoma. We would like to report two cases where the clue to the hepatic origin
      of CUP was the presence of cytoplasmic staining for TTF-1. Description of both
      cases with pertinent literature review will be offered. Two patients were seen at
      the James H. Quillen Veterans Administration Medical Center (VAMC), where one had
      a right chest wall mass with previous history of prostatic carcinoma and the
      other was found to have a lytic rib lesion with a previous history of lung
      squamous cell carcinoma. FNA and core biopsies were performed on both lesions
      where the initial pathological interpretations were nonsmall cell carcinoma. IHS
      revealed positivity for cytokeratin-7 and granular cytoplasmic staining for TTF
      1. Further workup using stains for Alpha Fetoprotein, Hepatocyte Paraffin (Hep
      Par 1) and CEA confirmed the diagnosis of metastatic hepatocellular carcinoma
      (HCC). Paying attention to cytoplasmic staining for TTF-1 in any CUP should
      prompt further pathological and clinical evaluation to rule out hepatocellular
      carcinoma.

PMID- 22359994
TI  - Music therapy to promote movement from isolation to community in homeless
      veterans.
AB  - The U.S. Department of Veterans Affairs' Operation Stand Down has done much to
      address homeless needs among veterans. Gaining client trust is central to the
      effectiveness of the program. Music therapy has been found beneficial in moving
      individuals from isolation to community. We report our experience with
      participatory music therapy in Operation Stand Down and offer this as a
      legitimate intervention to enhance client participation.

PMID- 22359995
TI  - Put on your armor!

PMID- 22359996
TI  - History for the future (of nursing).

PMID- 22359997
TI  - "To help a million sick, you must kill a few nurses": nurses' occupational
      health, 1890-1914.
AB  - Although nursing is recognized today as a serious occupational health risk,
      nursing historians have neglected the theme of occupational health and individual
      nurses' experience of illness. This article uses the local history of three case
      study institutions to set nurses' health in a national context of political,
      social, and cultural issues, and suggests a relationship between nurses' health
      and the professionalization of nursing. The institutions approached the problem
      differently for good reasons, but the failure to adopt a coherent and consistent
      policy worked to the detriment of nurses' health. However, the conclusion that
      occupational health was somehow neglected by contemporary actors was,
      nevertheless, erroneous and facilitated omission of the subject from historical
      studies concentrating on professional projects and the wider politics of nursing.
      This article shows that occupational health issues were inexorably connected to
      these nursing debates and cannot be understood without reference to professional
      projects.

PMID- 22359998
TI  - "Who would know better than the girls in white?" Nurses as experts in postwar
      magazine advertising, 1945-1950.
AB  - American advertising in the period immediately following the Second World War
      portrayed nurses as trusted advisers and capable professionals and frequently
      pictured them performing skilled work, including dispensing medicine and
      assisting in surgery. Advertisements published in a range of magazines whose
      target audiences varied by gender, race, age, and class show that nurses in
      postwar advertisements embodied two broad categories of representation: (a)
      medical authority, scientific progress, and hospital cleanliness; and (b)
      feminine expertise, especially in female and family health. Typically portrayed
      as young white women--although older nurses were occasionally depicted and black
      nurses appeared in advertisements intended for black audiences-nurses were
      especially prominent in advertisements for menstrual and beauty products, as well
      as products related to children's health. Although previous scholarly
      examinations of nurses in postwar mass media have emphasized their portrayal as
      hypersexual and incompetent, this investigation posits postwar advertising as a
      forum that emphasized nurses' professionalism, as well as complex expectations
      surrounding women's professional and domestic roles.

PMID- 22359999
TI  - Maternal expectations: new mothers, nurses, and breastfeeding.
AB  - By the middle of the 20th century, breastfeeding rates had fallen to less than
      20% in some areas of the United States. Despite these grim statistics, many
      mothers continued to seek information, advice, and the experience of
      breastfeeding their infants. This article explores the role that nurses played in
      these women's struggles to breastfeed in the years between the end of World War
      II and the 1970s. The role of the nurse in shaping the meaning and experience of
      breastfeeding in America has been an important, albeit often overlooked, part of
      the history of infant feeding. In addition to exploring the ways in which
      hospital policies and structures shaped nurses' relationships with breastfeeding
      mothers, this article looks at how different maternal ideologies influenced the
      nature of these (mostly) same-sex interactions. This article argues that the
      ideas about, and experiences with, motherhood had important implications for how
      nurses and mothers approached the practice of breastfeeding in the hospital.

PMID- 22360000
TI  - Community mental health nursing in Alberta, Canada: an oral history.
AB  - Community mental health nurses had a central role in the construction of new
      rehabilitative practices and community mental health services in the 1960s and
      1970s. The purpose of this article is, first, to explore how nurses understood
      and created their new role and identity in the turbulent context of
      deinstitutionalization. The development of after care services for patients
      discharged from Alberta Hospital in Ponoka (AH-Ponoka), a large mental
      institution in Calgary, in the Canadian province of Alberta, will be used as a
      case study. I specifically focus on the establishment of outpatient services in a
      new psychiatric department at Foothills General Hospital in Calgary. Second, I
      examine how deinstitutionalization itself shaped community mental health nurses'
      work. Oral history interviews with nurses and other mental health professionals,
      who had a central role in this transformation process, provide a unique lens
      through which to explore this social change. The article concludes that new
      rehabilitative, community-based mental health services can better be understood
      as a transformation of former institutional practices rather than as a definite
      break with them.

PMID- 22360002
TI  - China confidential: methodological and ethical challenges in global nursing
      historiography.
AB  - As the history of nursing as a field of scholarship expands its global
      consciousness, it seems timely to join other scholars of international history in
      rethinking conventional approaches to historiography. The lament by mission
      scholars at the invisibility of nurses and indigenous workers in historical
      mission records coincides with calls by China scholars to reconsider traditional
      reliance on English-language data generation and interpretation for an English
      speaking audience. In a similar way, nursing scholars are challenging historians
      of nursing to find ways to build a body of scholarship and a cadre of scholars
      that can open up new linguistic and cultural space for vibrant discussion and
      dialogue. Drawing on Sonya Grypma's research on the role of missionary nurses in
      the development of modern nursing in China and based on a series of interviews by
      the authors in China of participants with ties to a former Canadian mission
      hospital, we explore methodological and ethical challenges in global nursing
      historiography. By offering insights gleaned from our early attempts to capture
      voices not included in conventional mission records, we hope to stimulate more
      dialogue about conceptual and structural issues central to a "new" global nursing
      historiography.

PMID- 22360001
TI  - "Time enough! Or not enough time!" An oral history investigation of some British
      and Australian community nurses' responses to demands for "efficiency" in health
      care, 1960-2000.
AB  - Oral history methodology was used to investigate the perspectives of retired
      British district nurses and Australian domiciliary nurses who had practiced
      between 1960 and 2000. Interviews yielded insights into the dramatic changes in
      community nursing practice during the last four decades of the 20th century.
      Massive changes in health care and government-led drives for greater efficiency
      meant moving from practice governed by "experiential time" (in which perception
      of time depends on the quality of experience) to practice governed by "measured
      time" (in which experience itself is molded by the measurement of time). Nurses
      recognized that the quality of their working lives and their relationships with
      families had been altered by the social, cultural, and political changes,
      including the drive for professional recognition in nursing itself, soaring
      economic costs of health care and push for deinstitutionalization of care.
      Community nurses faced several dilemmas as they grappled with the demands for
      efficiency created by these changes.

PMID- 22360004
TI  - Registration of clinical trials--a regional perspective.

PMID- 22360003
TI  - Historical thinking and the shaping of nursing identity.
AB  - Nursing history was a core component of nurse training programs as early as 1907,
      when American Adelaide Nutting published her three-volume history. However, it
      had all but disappeared by the end of the 20th century, supplanted by other
      subjects. The University of Ottawa Nursing History Research Unit developed two
      online nursing history courses, in English and French, respectively, which proved
      popular and prompted substantial interest in the reintroduction of nursing
      history to our curriculum. This article presents findings of a study that
      examined the concept of "historical thinking"-what it is, how it develops, and
      what it contributes to practice-based professions-based on student postings in
      these courses. Analysis suggests that primary sources and critical appraisal
      skills are keys to the formation of historical thinking, and that these courses
      fostered a strong sense of professional identity among participants who often
      lamented lack of previous exposure to nursing history. Online nursing history
      courses can capitalize on e-learning technologies, and fit crowded curricula and
      student learning styles, while extending the reach of historians beyond
      traditional university walls.

PMID- 22360005
TI  - Knowledge, attitudes and practices about leishmaniasis among cutaneous
      leishmaniasis patients in Aleppo, Syrian Arab Republic.
AB  - Cutaneous leishmaniasis (CL) is endemic in Aleppo and yet the knowledge,
      attitudes and practices (KAP) of CL patients in Aleppo has never been studied. We
      conducted a KAP study among 70 CL patients attending 4 clinics in Aleppo.
      Participants were interviewed at recruitment and then at the end of treatment to
      ascertain their views on access to treatment and the quality of care provided.
      The mean age of respondents was 32.3 (SD 12.4) years and 59% were female. Most
      respondents referred to the disease as "one-year sore", linked it to insect bites
      and believed it was not contagious. Most believed it was preventable by the use
      of bednets and insecticides and knew the treatment mode. Only 26 (37%)
      respondents completed the second part of the questionnaire after treatment. Most
      of these (80%) rated the quality of care as acceptable or better. Assessment f
      the quality as "bad" correlated with failure to complete follow-up.

PMID- 22360006
TI  - Factors associated with the spread of dengue fever in Jeddah Governorate, Saudi
      Arabia.
AB  - Dengue fever resurged sharply in Jeddah in 2004 and rose to 1308 cases in 2006.
      This case-control study determined factors potentiating the spread of the disease
      to provide an epidemiological baseline to help dengue control. All (650)
      suspected cases of dengue in Jeddah in 2007 were eligible for inclusion. Cases
      were those confirmed with dengue by laboratory investigations (n = 244) and
      controls those confirmed negative (n = 406). Of these, 129 cases and 240 controls
      could be contacted and were included in the study. Variables found significant in
      the bivariate analysis were included in a logistic regression analysis. The
      presence of stagnant water in indoor drainage holes (OR = 4.9), indoor larvae (OR
      = 2.2), nearby construction sites (OR = 2.2), and older age (OR = 1.2) were
      independent determinants of dengue infection (P<0.01 for all). Face-to-face
      health education significantly decreased the risk of dengue infection. Efforts
      are needed to control the modifiable factors identified in this study with
      emphasis on health education.

PMID- 22360007
TI  - A distinct autosomal recessive ocular anomaly in Chaharborj, Islamic Republic of
      Iran.
AB  - In Chaharborj, a village in north-eastern ofthe Islamic Republic of Iran, a high
      prevalence of congenital blindness (1.1%) has been reported. The clinical
      findings have not been fully described. We therefore assessed the clinical
      aspects of this condition in a case series of 20 congenitally blind patients and
      24 of their parents. All patients had been blind since birth. There was anterior
      segment dysgenesis and retinal non-attachment in all patients. There were no
      systemic anomalies. Histopathologically, there was iridocorneal adhesion, normal
      angle structure and retinal dysplasia. No significant difference was found in the
      frequency of different HLA class I alleles compared with the general population.
      The anomaly causing congenital blindness in these patients has components of both
      anterior and posterior segment dysgenesis. It appears to be a distinct entity
      with an autosomal recessive pattern of inheritance.

PMID- 22360008
TI  - Early outcomes of pandemic influenza (H1N1) 2009 surveillance in Abu Dhabi
      Emirate, May-August 2009.
AB  - Soon after the initial detection of cases of pandemic H1N1 infection in Mexico, a
      new H1N1 surveillance system was set up in Abu Dhabi Emirate in May 2009. This
      paper reports on the outbreak from May to August 2009. A total of 356 cases were
      confirmed from 20 May 2009 to 16 August 2009. The incidence of confirmed H1N1
      cases was 18.5 per 100 000. Their ages ranged from <1 month to 62 years, with a
      median age of 20 years. The incidence was 18.6 per 100 000 among both males and
      females. The incidence among United Arab Emirates nationals was higher than
      expatriates (66.6 versus 5.2 per 100 000). No death attributable to H1N1 was
      reported. A low-grade H1N1 infection evolved in the Emirate with an incidence
      lower than some other countries, possibly because of the pandemic being in the
      early stages, perhaps coupled with under-reporting.

PMID- 22360009
TI  - Isolation and screening of methicillin-resistant Staphylococcus aureus from
      health care workers in Libyan hospitals.
AB  - This is the largest Libyan study to date to investigate the prevalence and
      antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus
      (MRSA) among health care workers in Tripoli, Libya. A total of 569 doctors and
      nurses from 4 main hospitals were screened for MRSA with specimens collected from
      the anterior nares. Isolates from 109 of the 569 subjects (19%) were confirmed as
      MRSA by polymerase chain reaction assay; the majority (98/109) were from a
      general hospital. Antimicrobial resistance patterns tested by disk diffusion were
      as follows: erythromycin (74%), ciprofloxacin (77%), clindamycin (20%),
      trimethoprim/sulfamethoxazole (50%), quinuprisin/dalfopristin (19%), vancomycin
      (12%) and mupirocin (5%). Eighteen isolates exhibited macrolide-lincosamide
      streptogramin B resistance (MLSB): 6 were MLSBi and 12 were MLSBc. The results
      provide evidence that Libyan health care workers could serve as MRSA carriers and
      play a role in the dissemination of MRSA to the public and other workers.

PMID- 22360010
TI  - Pediculosis capitis among primary-school children in Mafraq Governorate, Jordan.
AB  - Pediculosis capitis (head lice infestation) is a worldwide public health concern
      affecting mostly primary-school children. In a cross-sectional study in
      2009/2010, the prevalence of pediculosis capitis and some risk factors for
      infestation were investigated among 1550 randomly selected primary-school
      children in Mafraq governorate, Jordan. The prevalence of pediculosis capitis was
      26.6%. There were significant differences in the prevalence between girls (34.7%)
      and boys (19.6%), rural (31.2%) and urban (23.5%) residents, and history of
      infestation in the previous year (57.4%) versus no history (11.5%), as well as
      between children of different ages, family size and income (P<0.001). Longer hair
      length, lack of bathing facilities, low frequency of hair-washing and bathing,
      and sharing of articles (e.g. combs, scarves) were significantly associated with
      infestation (P<0.001). The prevalence of infestation was higher than reported in
      previous studies in Jordan (< 14%). Programmes are needed to increase awareness
      of pediculosis capitis and the importance of good personal hygiene.

PMID- 22360011
TI  - Survey of skin disorders in newborns: clinical observation in an Egyptian medical
      centre nursery.
AB  - The frequency of neonatal skin disorders has not been well studied in Egypt. Our
      aim was to address patterns of dermatological changes in a sample of Egyptian
      newborns. In a descriptive prospective cohort study 600 newborns in Sohag
      University hospital nursery were dermatologically examined within the first 5
      days of birth. Skin disorders were detected in 240 neonates (40.0%). Birthmarks
      were found in 100 neonates (16.7%), mainly melanocytic type (mongolian spots in
      11.7% and congenital melanocytic naevi in 2.7%). Fungal skin infections,
      including oral moniliasis, fungal infection in the napkin area or candidal
      intertrigo, were detected in 13.3% and bacterial infections in 1.3% of neonates.
      Comparisons with other studies worldwide indicated a higher rate of fungal
      infections and lower rate of birthmarks in our study. Routine neonatal
      dermatological evaluation is recommended, especially in view of the high rate of
      fungal skin infections.

PMID- 22360012
TI  - [Reasons for using emergency departments of major hospitals in Greater Tunis].
AB  - Tunisia, similar to many countries, has a problem of overcrowding of the
      emergency departments (ED). This study aimed to analyse the reasons for using
      EDs, and to describe the seriousness of the attendees' condition and their
      itinerary before their arrival at ED. This cross-sectional study in 2009 was
      conducted in ED of 4 hospitals in GreaterTunis and targeted 1058 patients of both
      sexes, aged 18 years, with stratification according to time of day of
      presentation to ED (morning, afternoon and evening). Information was recorded on
      the sociodemographic characteristics of the study participants, reasons for
      choosing ED, time of and reason for consultation, diagnosis and severity of
      illness. Over half the patients (52.5%) were male and the mean age was 46.0 (SD
      18.1) years. The main reasons for choosing the ED were: speed (54.0%) and ease of
      access (47.7%) of ER and occurrence of an acute episode (26.4%). Patients with
      serious illness accounted for only 6.3% of those interviewed. Implementation of
      good practices and better coordination between public and private services and
      the ED are needed to reduce unnecessary visits to ED.

PMID- 22360013
TI  - Sensitivity and specificity of ultrasound in the diagnosis of acute appendicitis.
AB  - The aim of this study was to evaluate the sensitivity and specificity of
      ultrasound in the diagnosis of acute appendicitis at Al-Shefa hospital, Gaza
      Strip, Palestine. Patients who had appendicitis diagnosed by ultrasound over the
      study period (n = 180) underwent surgical excision of the appendix. The negative
      appendectomy rate was low, with only 4.4% (8/180) false positives. A
      significantly higher false diagnosis rate (false negatives + false positives) was
      obtained in female patients than in males: 38.5% versus 6.2%. A high proportion
      of falsely diagnosed cases had abnormal weight (overweight or obese) (82.1%). The
      overall sensitivity and specificity of ultrasound, using surgical outcome as the
      gold standard, were 84.8% and 83.3% respectively, and the positive and negative
      predictive values were 93.3% and 66.7% respectively. Sensitivity and specificity
      were higher in males (95.7% and 88.2% respectively) than females (84.6% and 71.4%
      respectively).

PMID- 22360014
TI  - Management of the use of public health pesticides in the face of the increasing
      burden of vector-borne diseases in the Eastern Mediterranean region.
AB  - The Eastern Mediterranean Region of the World Health Organization is facing an
      increasing burden of vector-borne diseases. Progress in controlling these
      diseases is compromised by the limited number of vector control interventions,
      most of which rely on the use of pesticides. Seventeen countries of the Region
      participated in a global survey that aimed to map and document registration and
      management practices for public health pesticides. This paper aims to draw the
      attention of policy- and decision-makers to the challenges the Region is facing
      in managing public health pesticides properly to control disease vectors and,
      based on the outcome of the survey, recommends a set of actions to guide national
      policy and to strengthen national capacity for the sound management and judicious
      use of public health pesticides.

PMID- 22360015
TI  - Efficacy of constitutional support to enhance access to essential medicines as a
      human right to health in the Eastern Mediterranean region.
AB  - Access to essential medicines is an element of the international agreements on
      the human right to health. This review summarizes the current situation
      concerning access to medicines in the Eastern Mediterranean Region (EMR) by
      examining the policies, constitutional provisions and other legal instruments of
      the Member States. The constitutions of 18 out of 22 EMR countries enshrine
      health as a human right (8 countries have a duty statement, 5 have a programmatic
      statement and 5 specify entitlement); only 4 EMR countries do not enshrine health
      as a human right in a clause in their constitution. More than half the countries
      (i.e. 12) have an official national medicines policy, 4 have a draft policy and 6
      have no national medicines policy. A total of 11 countries operate an essential
      medicines list. Realization of this right to health necessitates that duty
      bearers take all necessary legislative measures to respect, protect and fulfil
      this right.

PMID- 22360016
TI  - [Pharmacoepidemiolgy: regulatory basis, methodological approaches and scope].
AB  - Pharmacoepidemiology is a discipline that studies the use of drugs and evaluation
      of their beneficial or adverse effects on large populations. It requires
      compliance with laws and maintaining a regulatory approach in order to ensure
      confidentiality and protection of personal data. It also requires good knowledge
      of drugs and diseases and the use of the different available data sources.
      Pharmacoepidemiology incorporates epidemiological methods (cohort, case-control
      and cross-sectional studies) where the exposure is drug intake. These methods
      must be applied at the conception of the pharmacoepidemiological study in order
      to minimize the effect of bias hich can lead to false conclusions. This paper
      reviews the regulatory basis, methodological approaches and scope of
      pharmacoepidemiology.

PMID- 22360017
TI  - Birthing in the Arab region: translating research into practice.
AB  - The Choices and Challenges in Changing Childbirth research network is a regional
      collaboration among 4 countries in the Arab region, namely Egypt, Lebanon,
      Palestine and Syrian Arab Republic, providing evidence of childbirth practices
      and identifying areas amenable to change. Studies that have been conducted in the
      region pinpoint problems in the quality of maternity services and a lack of
      women's involvement in the process of maternity care. The network aims to change
      childbirth practices by selecting research areas most likely to influence
      practices, by supportingthe process of obtaining regionally relevant evidence of
      a high standard and by assigning importance to dissemination and networking
      activities. This paper draws on the experience of the network in selecting
      strategies to approach different challenges and discusses the barriers facing
      this process.

PMID- 22360018
TI  - Should HBV or HCV positive surgeons refrain from operating.

PMID- 22360019
TI  - The relationship between exertional chest pain/dyspnoea--heart rate in patients
      with coronary artery disease using Exercise ToleranceTest.
AB  - OBJECTIVES: To observe the relationship between chest pain/dyspnoea-heart rate
      during exertion in patients with angiographically proved Coronary artery disease
      compared to patients having negative Exercise Tolerance Test in a private and
      public sector hospital. METHODS: This is an observational two centre study from
      Karachi in which 150 patients referred for Exercise ToleranceTest (ETT) at
      Ziauddin University Hospital, Clifton campus and National Institute of
      Cardiovascular Diseases Karachi were included. The period of study extended from
      September 2008 to March 2010. All patients performed a maximal progressive
      exercise on Bruce protocol. Age, Body Mass Index, target heart rate and risk
      factors of Coronary artery disease were noted for each patient. The resting heart
      rate and resting systolic Blood Pressure (BP) were noted. The maximum systolic
      BP, maximum heart rate, total exercise time and Multiples of resting oxygen
      consumption (METS) were recorded at the end of exercise. The chest pain and
      dyspnoea score were plotted against maximum heart rate. RESULTS: Out of 136, 51
      were ETT positive and 76 were ETT negative. The ETT positive were older in age,
      had lesser maximal heart rate, lesser total exercise time and lesser METS than
      ETT negative. Out of 51 ETT positive patients, 20 had chronotropic incompetence.
      CONCLUSION: In patients having positive ETT and referred for angiography, the
      chest pain-heart rate relationship correlated well with number of vessel disease.
      The dyspnoea-heart rate relationship was not different in the two groups.

PMID- 22360020
TI  - Effect of hyperventilation on electroencephalographic activity.
AB  - OBJECTIVE: To observe the effect of voluntary hyperventilation on
      electroencephalographic activity during routine EEG recording on patients
      referred to a tertiary care hospital. METHODS: This was an observational study
      conducted at Neurophysiology Lab, Department of Neurology at Liaquat National
      Hospital, Karachi from May 2007 to September 2007. Data of 326 patients was
      collected prospectively and analyzed by SPSS version 10.0. At least 3 minutes
      voluntary hyperventilation was performed by the subjects. All those patients who
      were able to perform voluntary hyperventilation adequately were included in the
      study. RESULTS: Of 326 recordings, 256 (78.8%) were normal and 69 (21.2%) were
      abnormal. Focal epileptiform discharges were identified in 8.6% and generalized
      in 8.3% of subjects. Physiological slowing was found in 31 records. Out of 55
      epileptics, 3 had discharges only during HV and 9 had increase in epileptiform
      discharges. CONCLUSION: Hyperventilation has significant effect on background
      rhythm during EEG recording. It is a useful activation method utilized to
      increase the yield of EEG.

PMID- 22360021
TI  - To assess the levels of zinc in serum and changes in the lens of diabetic and
      senile cataract patients.
AB  - OBJECTIVE: To assess the levels of zinc in serum and changes in the lens of
      diabetic and senile cataract patients METHODS: A comparative cross sectional
      study was done at LRBT (Layton Rehmatullah Benevolent Trust) free eye hospital
      Mandra from July 2010 to August 2010. Twenty Type 2 diabetic patients with
      cataracts and 20 patients without diabetes of senile cataract were included in
      the study. Glucose levels were determined by glucose oxidase method and zinc
      levels measured by colorimeteric method (RANDOX). RESULTS: The statistical
      analysis showed a statistically significant decrease in zinc levels in diabetic
      patients with cataract when compared to individuals with senile cataract (P
      <0.05). In senile lenses multilayering of cells, wrinkling of the lens capsule,
      and apoptotic cell death were seen, but in diabetic lenses number of cells
      decreased and cells were smaller as compared to senile lenses. The results were
      not statistically significant P >0.05. CONCLUSION: Our findings in this study
      show a relationship between zinc deficiency and increased occurrence of cataract
      among people with diabetes.

PMID- 22360022
TI  - Accuracy of intra-operative frozen section in the diagnosis of ovarian tumours.
AB  - OBJECTIVES: To compare frozen-section results with definitive histopathological
      results of ovarian tumours diagnosed intra operatively at the Zonguldak Maternity
      Hospital, Zonguldak, Turkey. METHODS: The definitive histopathological results of
      278 patients who underwent surgery between January 2002 and December 2008 for
      ovarian masses and on whom frozen sectioning was performed were evaluated
      retrospectively. After exclusion of 12 patients for whom a definitive result
      could not be obtained from frozen sections, the results of 266 patients' frozen
      sections were compared with those from permanent sections. RESULTS: Data of 266
      patients was analyzed. The results of frozen sections were 235 (88.3%) benign, 11
      (4.2%) borderline and 20 (7.5%) malignant. The sensitivity was 100% for the
      benign tumours, 77.8% for the borderline tumours and 71.4% for the malignant
      tumours. The specificity of frozen section was 83.8%, 98.4% and 100% for the
      benign, borderline and malignant tumours, respectively. CONCLUSIONS: Frozen
      sections have adequate sensitivity and specificity at the Zonguldak Maternity
      Hospital, Turkey, and can be safely used to guide the intraoperative management
      of ovarian masses. False-positive and -negative ratios are low.

PMID- 22360023
TI  - Foreign body in the upper airway and oesophagus: a seven years study from Iran.
AB  - OBJECTIVE: To determine the frequency of foreign body, its location and clinical
      symptoms in patients with symptoms or positive history of foreign body swallowing
      and to assess the role of endoscopy in the management of foreign body removal.
      METHODS: All patients referred to the Ear, Nose, Throat emergency ward of a
      general hospital in Kerman-Iran with a positive history of swallowing foreign
      body and presence of clinical symptoms and/or a suspicious radiological findings
      in favour of esophages foreign body in the period between April, 2001 and
      September, 2008 were evaluated. Patients undergoing esophagoscopy were 160. Data
      was analyzed by t test and spearman correlation coefficient. RESULTS: Among 160
      participants in this study, 82 (51.3%) were male .The patients' mean age was 36
      +/- 21.7 years. Among all the participating patients, 39 (24.4%) were below 18
      years age. There was no history of foreign body being swallowed in 37 cases. A
      total number of 123 cases had foreign bodies, the most commonly found foreign
      body was bone which was found in 46 patients (37.4%). While, the most common
      object swallowed in children was coin. Symptoms in all age groups was pain and
      audinophagia and second was dysphagia. Most of foreign bodies were stuck in the
      pharynx (50.6%) and the commonest place was 5cm below the cricopharyngeals
      junction (33%). There was no significant difference in the location of foreign
      bodies in males and females. The period between swallowing foreign body and
      referring to the hospital was less than a day in 115 cases (72%). There was no
      significant difference between the time taken to refer to the hospital and
      patients' sex, location and type of foreign body (P>0.05). The mentioned gap
      increased with age r = 0.21 p = 0.007. CONCLUSION: The most common foreign body
      found in adults was bone and in children it was a coin. The most frequent site
      where the foreign body was lodged was 5cm below the cricopharyngcal junction.

PMID- 22360024
TI  - PRECEDE educational model for controlling iron-deficiency anaemia in Talesh,
      Iran.
AB  - OBJECTIVES: To determine the effect of applying the PRECEDE educational model as
      a framework for controlling iron defiency anaemia (IDA) among high school girl
      students. METHODS: This Quasi-experimental study was conducted between April and
      July 2009 at Isfahan, Iran. Using a simple random sampling technique, a total of
      72 students were selected and divided in two intervention and control groups.
      Data gathering tools were questionnaire and laboratory tests (Hb, Hct, and
      Ferritin). After using the Precede educational model, (model for, Planning health
      education & health promotion programme and policies) results were analyzed with
      SPSS software and appropriate statistical tests (Independent-Sample T test and
      Chi- Square). RESULTS: After education, the mean scores of awareness and attitude
      as predisposing factors, applying of educational resources and participation in
      educational programmes such as enabling factors, encouragement of parents,
      teachers and friends as reinforcing factors had a significant increase in the
      intervention group compared with control group (p < 0/001). Also, in terms of
      blood indices there was a significant difference between the two groups, before
      and after educational programme (p < 0/001). CONCLUSION: Results of this study
      indicate positive effect of model base educations especially PRECEDE model in
      preventive health cares such as IDA prevention. Therefore, using of health
      education models for planning and implementing educational programmes is
      recommended.

PMID- 22360025
TI  - Effects of Nigella sativa and albendazole alone and in combination in Toxocara
      canis infected mice.
AB  - OBJECTIVE: Nigella sativa extract has been used in the Middle East as a
      traditional medicine for several complaints. We aimed to evaluate the
      biochemical, histopathological and hematologic changes in Toxocara canis-infected
      mice after treatment with Nigella sativa extract, albendazole or a combination of
      both. METHODS: This comparative study was conducted between June and July 2008 at
      the Itarran University Saniturla Turkey. Sixty healthy adult BALB/c male mice
      were randomly divided into six groups (D0-D5). Mice in groups D1-D5 received 500
      embryonated T. canis eggs via esophageal tube. Groups DO and D1 served as a non
      infected sham group and an infected control group, respectively. Groups D2 and D3
      received 100 and 200 mg/kg N. sativa extract (NSE), respectively. Group D4
      received 100 mg/kg albendazole. Group D5 received the combination dose (100+100
      mg/kg NSE+albendazole). RESULTS: Treatment with N. sativa of both doses or the
      combination dose of N. sativa and albendazole reduced the degree of inflammation
      and necrosis, lead to a reduction in the percentage of eosinophils and decreased
      the elevated liver enzyme levels. CONCLUSION: These results indicate that N.
      sativa has a potent effect in protection against organ damage induced by T. canis
      infection.

PMID- 22360026
TI  - The role of computed tomography for identifying mechanical bowel obstruction in a
      Pakistani population.
AB  - OBJECTIVE: To retrospectively review our experience of CT scan in cases with a
      final diagnosis of surgically confirmed mechanical bowel obstruction. METHODS: It
      is a retrospective analytical study, done from 2003 to 2008. All adult patients
      having undergone laparotomy in addition to a preoperative abdominal CT scan over
      a 5 year period were identified through the medical records and their case notes
      reviewed. Taking surgery to be the gold standard for diagnosing mechanical bowel
      obstruction, we compared results of the CT with operative findings to determine
      the sensitivity, specificity, positive and negative predictive values of CT
      scans. The data was analyzed using SPSS version 16.0. RESULTS: A total of 271
      patient records were reviewed. The mean age was 46 +/- 19 years and (64%) were
      men. Mechanical intestinal obstruction was found in 104 patients on laparotomy
      and CT scan had diagnosed 97 of these. The sensitivity and specificity was 93%
      respectively. CT scanning correctly identified the cause of the obstruction in 72
      (74%) cases. The common reasons for bowel obstruction identified by surgery were
      adhesions 29 (40%), neoplasm 12 (17 %) and hernias 7 (10%). CONCLUSION: CT scans
      are reliable at diagnosing intestinal obstruction with a high sensitivity and
      specificity but they are not as accurate at defining the etiology of the
      obstruction.

PMID- 22360027
TI  - Outcome of trimodality protocol for invasive bladder cancer patients at Karachi,
      Pakistan.
AB  - OBJECTIVES: To evaluate the outcomes of patients with muscle invasive bladder
      cancer managed by trimodality protocol with assessment of factors that may
      predict treatment response, risk of recurrences and survival of such patients in
      our population. METHODS: A prospective, single arm study was conducted between
      July 2006 and December 2009 at the Sindh Institute of Urology and Transplantion,
      Karachi. One hundred and sixteen patients with muscle invasive bladder cancer T2
      T3N0M0 were treated with concurrent chemoradiation (total dose 6500 cGy) after
      maximal transurethral resection. Complete response was defined as no tumour seen
      on check cystoscopy and biopsy. The disease control and overall survival were
      determined by Kaplan and Meier method and statistical inferences with the log
      rank test. Cox regression analysis was used to find different prognostic factors.
      RESULTS: At the median follow up of 36 months (14-43), out of total 116,
      62(51.6%) surviving patients the bladder was functioning well, while 18(15%) had
      local recurrence; in 9 patients superficial tumour recurred and required further
      transurethral resection and intravesical drug therapy and nine patients who had
      muscle invasive recurrence; underwent radical cystectomies. Concurrent
      chemoradiation was well tolerated. The overall survival at 3 years was 54%.
      Initial complete response, primary tumour stage and absence of hydronephrosis
      were the most important prognostic factors for survival (all p=<0.0001).
      CONCLUSION: Trimodality treatment was found to be an effective therapy in
      patients with invasive bladder cancer and complete TURBT, tumour stage and no
      hydronephrosis at time of presentation were found important prognostic factors
      for treatment response, disease free and over all survival rates.

PMID- 22360028
TI  - Would pulsed radiofrequency applied to different anatomical regions have
      effective results for chronic pain treatment?
AB  - OBJECTIVE: To observe the effect of Pulsed radiofrequency on patients presenting
      with complaints of chronic pain. METHODS: It was a retrospective cross sectional
      study which included patients with chronic pain who did not respond to
      conventional treatment.The study was conducted at the Pain Management Centre,
      Dicle University, Diyarbakir, Turkey from October 2008 to September 2010. The
      applications of Pulsed radiofrequency (PRF) were made under the guidance of C-arm
      fluoroscopy, local anaesthesia, and sedoanalgesia. The intervention types applied
      consisted of sacroiliac intraarticular, heel, sciatic nerve and impar ganglion
      Pulsed radiofrequency. Visual Analogue Scale (VAS) was used for pain
      assessment.Sacroiliac intraarticular PRF was applied to nine patients, impar
      ganglion PRF to eight patients, heel PRF to four patients and sciatic nerve PRF
      was applied to three patients. RESULTS: The mean age of the patients was 41.3 +/-
      16.9 (range 15-77) years, 15 (62.5%) were females. The mean follow-up period was
      8.5 +/- 5.4 months. A minimum 50% decrease was determined in the VAS scores of 16
      (66.7%) patients compared to the initial values. The patients who had > or = 50%
      decrease in their VAS scores in the sacroiliac group was 55.6. This value was
      75.0, 75.0 and 66.7 in the impar, heel and sciatic nerve groups respectively. No
      early- or late-term complications were observed in any of the patients.
      CONCLUSIONS: P Pulsed Radiofrequency implementation was found to be an effective
      and safe method for chronic pain treatment in our centre.

PMID- 22360029
TI  - DREEM on: validation of the Dundee Ready Education Environment Measure in
      Pakistan.
AB  - OBJECTIVES: To validate DREEM in medical education environment of Punjab,
      Pakistan. METHODS: The DREEM questionnaire was anonymously collected from Final
      year Baccalaureate of Medicine; Baccalaureate of Surgery students in the private
      and public medical colleges affiliated with the University of Health Sciences,
      Lahore. Data was analyzed using Principal Component Analysis with Varimax
      Rotation. RESULTS: The response rate was 84.14 %. The average DREEM score was
      125. Confirmatory and Exploratory Factor Analysis was applied under the
      conditions of eigenvalues >1 and loadings > or = 0.3. In CONFIRMATORY FACTOR
      ANALYSIS, Five components were extracted accounting for 40.10% of variance and in
      EXPLORATORY FACTOR ANALYSIS, Ten components were extracted accounting for 52.33%
      of variance. Total 50 items had internal consistency reliability of 0.91
      (Cronbach's Alpha). The value of Spearman-Brown was 0.868 showing the reliability
      of the analysis. In both analyses the subscales produced were sensible but the
      mismatch from the original was largely due to the English-Pakistan contextual and
      cultural differences. CONCLUSION: DREEM is a generic instrument that will do well
      with regional modifications to suit individual, contextual and cultural settings.

PMID- 22360030
TI  - Ameliorating effects of dexpanthenol in cerebral ischaemia reperfusion induced
      injury in rat brain.
AB  - OBJECTIVE: To study the attenuating effect of Dexpanthenol (Dxp) provitamin B5 on
      neuronal damage after cerebral ischaemia/reperfusion. METHODS: This was a
      randomized, controlled experimental study conducted at the Islamic Azad
      University, Tabriz, Iran, from April to September 2008. Male wistar rats were
      divided into 4 groups randomly (n=13): 1- sham group, Group 2 :two hours
      occlusion of middle cerebral artery (MCA) and 24 hours reperfusion. Group 3: two
      hours occlusion of MCA and 24 hours reperfusion + Dxp (250mg/kg) since 3 days
      before ischaemia. Group 4: two hours occlusion of MCA and 24 hours reperfusion
      which had received Dxp (500mg/kg) since 3 days before ischaemia. Glutathione
      (GSH) and malondialdehyde (MDA) levels were studied in brain tissue and numbers
      of cornu ammonis (CA1 and CA3) pyramidal neurons were studied with light
      microscopy. RESULTS: The GSH levels were significantly higher in groups 3 and 4
      as compared with group 2. In group 3 and group 4 animals, the MDA levels were
      significantly lower than in group 2 (P < 0.05). Numbers of CA1 and CA3 neurons
      were completely normal in appearance in the group 1. The surviving neurons in the
      CA1 and CA3 subfield were markedly decreased in number, in group 2 (P < 0.05).
      CONCLUSION: Our pathologic and biochemical study has proven positive effect of
      Dxp on protection of cerebral tissue after I/R. The present findings correlate
      with previous studies on the protective effects of Dxp against cell and tissue
      injury by I/R.

PMID- 22360031
TI  - Efficacy of valve replacement surgery in patients with severe pulmonary
      hypertension.
AB  - OBJECTIVES: To evaluate the safety of valve replacement surgery in rheumatic
      heart disease patients with severe pulmonary hypertension (SPH); defined as
      pulmonary artery systolic pressure (PASP > or = 60 mmHg) on patients operated for
      valve replacement at Tabba Heart Institute, Karachi. METHOD: From July 2005 to
      September 2007, total of 112 patients underwent valve replacement (AVR, MVR,
      AVR+MVR) at our institution. We retrospectively examined the patients with SPH.
      RESULTS: The male:female ratio was 8:16, age range 18 to 70 years. Data was
      entered in SPSS version 16. Student t test was used for analyzing the qualitative
      data and chi-square for the quantitative data. Each case was reviewed on its
      merit and patient safety maintained by the cardiology and anaesthesia team.
      Twenty four patients had SPH (range; 60 to 120 mmHg, mean 77.38). Fifteen
      underwent MVR; AVR one and 7 had AVR+MVR and one MVR + CABG. Three bioprosthetic
      and 21 mechanical prostheses were implanted. LVEF ranged from 47% to 75 %. Left
      atrium size ranged from 35 mm to 160mm. Out of 24 patients 10 patients had giant
      left atria (>6.5 cm). Four patients had dilated RV (range; 17mm to 31 mm). We
      observed no operative mortality, one patient developed post-operative pulmonary
      hypertensive crisis and one developed acute renal failure. The incidence of post
      op atrial fibrillation was 12.5%. All patients were NYHA class IV pre-operatively
      and NYHA class I or II post-operatively. There were no neurological or pulmonary
      complications in our series and none of the patients had re-exploration for
      bleeding. CONCLUSION: Cardiac surgery can be successfully performed with an
      acceptable morbidity and very low mortality in patients with long standing
      valvular disease and SPH.

PMID- 22360032
TI  - Tremors and its determinants: a 7-years study at a secondary care hospital.
AB  - OBJECTIVE: To evaluate the cause, frequency and determinants of tremors at
      secondary care settings. METHODS: A hospital based cross-sectional study for
      seven years (2002-2009) was carried out at Sindh Govt. Hospital (SGH) Liaqatabad
      No.10, Karachi. Sample size was 403 and sampling technique was Convenience
      sampling. A data collection form was designed and all essential variables were
      recorded regarding age, gender, residence, complaints and their duration,
      education status, profession, co-morbid and investigations performed. The results
      were analyzed using SPSS 16.0. RESULTS: Out of 403 patients 247 (61.5%) were
      males and 156 (38.5 %) were females. The mean age of the patients was 55.9 +/-
      14.2 years. The male to female ratio was 2: 1.6. Enhanced physiological tremor
      was the most frequent diagnosis. Among whom, females of 40-60 years were mostly
      affected. Essential tremors were mainly coarse in amplitude, whereas commonest
      fine tremors were diagnosed as Enhanced Physiological tremor. CONCLUSION:
      Evaluation of patients with tremors showed males to be more affected with
      essential tremors being the commonest encountered. Orthostatic tremor was rare.
      Essential tremors were diagnosed by exclusion.

PMID- 22360033
TI  - Magnesium deficiency in heart failure patients with diabetes mellitus.
AB  - OBJECTIVE: To assess the serum magnesium level in heart failure patients with
      diabetes mellitus. METHODS: A case-control study was conducted at Basic Medical
      Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, in
      collaboration with National Institute of Cardiovascular Diseases (NICVD),
      Karachi, from April 2003 to December 2003. The study included 45 diagnosed cases
      of heart failure with diabetes mellitus, between the age group 35-65 years. Serum
      magnesium and glucose levels were estimated and compared by using the student "t"
      test and p value (<0.01, <0.05, <0.001) were used to analyze the statistical
      significance. RESULTS: Out of 45 cases of heart failure, 15 were diabetic. Of
      these, eleven (73.3%) had low serum magnesium (<1.8 mg/dl), one (6.7%) was within
      normal range (1.8-2.0 mg/dl) and three (20%) were in the high level range(>2.0
      mg/dl). CONCLUSION: The study showed low serum magnesium level in heart failure
      patients with diabetes mellitus.

PMID- 22360034
TI  - Evolution of foetal echocardiography as a screening tool for prenatal diagnosis
      of congenital heart disease.
AB  - Congenital cardiac anomalies are the most common anomalies, with an estimated
      incidence of about 4-13 per 1000 live births. Proper perinatal and neonatal
      management is dependent upon accurate prenatal diagnosis. Approximately 10% of
      foetuses with cardiac abnormalities have identified risk factors; hence, most of
      the anomalies occur in pregnancies without prenatal risk factors. Foetal
      echocardiography allows for prenatal diagnosis of congenital heart disease and
      serves as a routine screening tool for congenital heart defects. Advanced
      technology, has not only allowed more accurate and early detection of cardiac
      abnormalities but has also improved the care and outcome of selected foetuses
      with severe cardiac malformations or arrhythmias. It can also identify patients
      for in-utero cardiac interventions. Prenatal diagnosis of congenital heart
      disease has allowed for better counseling and preparation of families regarding
      the expected prenatal development of the foetus as well as the anticipated
      postnatal management strategy and prognosis.

PMID- 22360035
TI  - An incidental solitary fibrous tumour in the retroperitoneum, coexisting with
      ipsilateral atrophic kidney.
AB  - Solitary fibrous tumour (SFT) is a relatively uncommon spindle-cell neoplasm that
      most commonly arises in the pleura, but which may also arise from other serosal
      surfaces outside the pleura. However, SFT is now known to affect various serosal
      surfaces including pericardium, peritoneum, retroperitoneum nasal and paranasal
      sinuses, thyroid, cavernous sinus or pituitary fossa. The histologic features of
      this lesion may create diagnostic confusion with a variety of other spindle-cell
      tumours. To the best our knowledge, no cases with SFT have been previously noted
      in the retroperitoneum coexisting with atrophic kidney. Herein, we report the
      unique association of a solitary fibrous tumour in the retroperitoneum coexisting
      with ipsilateral atrophic kidney in a 60-year-old man and define histopatological
      findings of this tumour.

PMID- 22360036
TI  - Insulinoma--a deceptive endocrine tumour.
AB  - Insulinoma is a deceptive endocrine tumour that can easily mislead even an astute
      clinician because of its bizarre and nonspecific symptom complex. A 45 year old
      woman presented with altered behaviour, seizures and spells of coma and was being
      treated as a case of hysterical neurosis. Biochemical and radiological
      investigations revealed fasting hypoglycaemia, endogenous hyperinsulinism, and a
      pancreatic parenchymal lesion. Removal of the pancreatic lesion resulted in
      abrupt restoration of euglycaemia and complete disappearance of patients'
      symptoms.

PMID- 22360037
TI  - Ovarian cancer during pregnancy.
AB  - The frequency of cancer during pregnancy is approximately 1 per 1000 live births.
      This rate may increase as more women postpone childbirth until later in life,
      when cancer becomes more frequent. Pregnancy affects management of the cancer,
      and the cancer affects the management of pregnancy. The most common malignancies,
      in order of frequency, are breast cancer, leukaemia and lymphomas as a group,
      melanoma, gynaecologic cancers, and bone tumours. Ovarian tumours are found in
      about 1 in 1000 pregnancies and 3-6% of these are malignant. Thus, ovarian cancer
      occurs in approximately 1 in 12,500-25,000 pregnancies. Here, we report a case of
      ovarian mucinous carcinoma that was diagnosed at 22 weeks of gestation. After
      conservative surgery, she was given three cycles of carboplatin chemotherapy. She
      delivered at 33 weeks of gestation and after undergoing surgery she was given six
      cycles of paclitaxel and carboplatin chemotherapy. The patient is now being
      followed by the oncology department with no evidence of disease.

PMID- 22360038
TI  - Axillary ectopic carcinoma of breast.
AB  - Carcinoma in ectopic breast tissue is rare. This is a case report of a 70-year
      old postmenopausal female, who presented with a painless mass in right axilla,
      diagnosed as invasive ductal carcinoma of ectopic breast tissue an excisional
      biopsy. Postoperatively she was put on tamoxifen, and remained well 10 months
      after surgery.

PMID- 22360039
TI  - Vesicocutaneous fistula.
AB  - Vesicocutaneous fistula, a very distressing condition has a tremendous impact on
      the quality of life of the patient. We report the case of a 30 years old woman ,
      who had caesarean hysterectomy after her third emergency caesarean section . She
      later developed abdominal wound infection which required resuturing. Since then
      she had been suffering from recurrent urinary tract infections and urinary leak
      through the abdominal wound during micturition. Urine analysis, urine culture,
      intravenous urogram, (IVU), voiding cystourethrogram (VCU), cystoscopy, and
      sinogram done in our institution revealed communication between urinary bladder
      and cutaneous opening in left edge of abdominal scar. Bladder was catheterized
      for 03 weeks and aseptic dressing on abdominal defect was done for the same
      duration. Antibiotics were also advised. Full recovery was achieved.

PMID- 22360040
TI  - Fracture dislocation of the lateral condyle and medial epicondyle of the humerus
      associated with complete radial nerve transection.
AB  - The combination of lateral condyle and medial epicondyle fractures of the humerus
      and a radial nerve transection is extremely rare. We could not find a similar
      case in the literature. Hereby we report such a case. An eight-year old female
      fell down while playing. She had wrist, thumb and fingers drop associated with
      hypoaesthesia over the first web space indicating radial nerve palsy. Plain X-ray
      of the left elbow showed fracture of the lateral condyle and avulsed fracture of
      the medial epicondyle. The Lateral condyle fracture was fixed with 2 screws and
      the medial epicondyle fracture was fixed with 2 K wires. The radial nerve was
      completely transected which was repaired primarily through a lateral approach.
      Six months later, the patient had full recovery of the wrist and elbow functions
      without any deformity.

PMID- 22360042
TI  - B-cell lymphoma of the brainstem with central neurogenic hyperventilation.
AB  - Non-Hodgkin's lymphoma of the brainstem is a rare entity. Central Neurogenic
      Hyperventilation (CNH), an associated manifestation of this disease, is an even
      rarer event. We report a case of an immunocompetent individual who presented to
      us with tachypnea and facial nerve palsy. Neuroimaging showed a Cerebellopontine
      angle tumour which on histopathology showed feature consistent with a Non
      Hodgkin's B-Cell Lymphoma. The patient went on to develop severe respiratory
      alkalosis with findings consistent with CNH. Chemotherapy with Methotrexate was
      started and high dose Dexamethasone was added to the regimen a month later.
      Radiologically, the tumour size decreased by 50% but the patient's clinical
      condition deteriorated. He eventually expired due to cardiopulmonary arrest. Some
      common clinical presentations of this disease and various diagnostic modalities
      and treatment options available to such patients are discussed.

PMID- 22360041
TI  - Cutaneous squamous cell carcinoma associated with proliferation of osteoclast
      like giant cells.
AB  - Proliferation of osteoclast-like giant cells in a cutaneous squamous cell
      carcinoma is a rare phenomenon and so far only four cases have been reported. In
      previous reports, osteoclast-like giant cells were admixed with sarcomatoid
      component of squamous cell carcinoma and it is therefore debatable if the
      osteoclast-like giant cells represent a reactive phenomenon or a part of the
      malignant tumour. A case of cutaneous squamous cell carcinoma associated with
      osteoclast-like giant cells is reported. However, sarcomatous component of
      squamous cell carcinoma was not identified in this case. Morphologically, the
      osteloclast-like giant cells appeared to be benign. The localization of the
      squamous cell carcinoma and the osteoclastic-like giant cells were separate from
      one another. Immunohistochemically, squamous cell carcinoma was positive for high
      molecular weight cytokeratin, cytokeratin-5 and p63, whereas the osteloclast-like
      giant cells were positive for histiocyte marker CD68 and vimentin and negative
      for epithelial markers supporting a reactive nature of osteoclast-like giant
      cells to the cutaneous malignancy.

PMID- 22360043
TI  - Raised CA125 serum level in tubercular peritonitis.
AB  - A 24-year old woman was admitted with a history of fever and pelvic pain. ESR and
      CA125 serum level were high and PPD test was negative. Ultra sound and CT
      evaluation detected free fluid in abdominopelvic cavity. Laparotomy showed
      fibrinous strands adhering to and fibrotic sac surrounding the components of
      abdominal cavity. Opening the sac, grey miliary nodules were spotted and
      pathologic examination revealed multiple granulomatous lesions. Diagnosed with
      TBP, patient underwent specific antibiotic therapy and her condition improved
      significantly following treatment. As laboratory findings and image analysis may
      be misleading in diagnosis of TBP, diagnostic approach of laparotomy and
      subsequent pathologic examination is of vital value--particularly in
      premenopausal female patients to preserve fertility.

PMID- 22360044
TI  - Respiratory dyskinesia--an under-recognized side-effect of neuroleptic
      medications.
AB  - Respiratory dyskinesia is an under-recognized side effect of neuroleptic
      administration. There are only few studies that have addressed the prevalence of
      respiratory dyskinesia in patients with tardive dyskinesia. Our case report
      highlights the need to regularly examine patients on antipsychotics for any
      evidence of dyskinetic movements including respiratory musculature. Since RD is
      underrecognized and misdiagnosed, early detection can improve long term prognosis
      as treatment options are few and usually of only limited effect. A 62-year-old
      Asian male, retired civil engineer, had more than 20 years history of depressive
      illness, developed antidepressant induced hypomania, and was given risperidone
      upto 1 mg per day. He developed extrapyrmidal side effects as tremors, rigidity
      and later dyskinetic movements of lips with shortness of breathing, dyspnoea,
      grunting or gasping. He was referred to the pulmonologist who got the neccessary
      medical work up done, which was normal. A diagnosis of respiratory dyskinesia was
      made. Respiratory dyskinesia is an under-recognised and distressing condition
      that clinicians need to be aware of when treating patients with anti-psychotic
      medications. And also there is a need to regularly examine patients on
      antipsychotics for any evidence of dyskinetic movements including respiratory
      musculature for early diagnosis and better outcome. This case report also is
      worth reading for professionals of other specialties also because of the
      presentation of this patient, it can be easily misdiagnosed and result in poor
      outcome.

PMID- 22360045
TI  - Medical marijuana: can we think about it?

PMID- 22360046
TI  - Use of traditional Chinese medication for post-stroke recovery.

PMID- 22360047
TI  - Assessment of frequency of diarrhoea in relation to drinking water among
      residents of Nurpur Shahan, Pakistan.
AB  - OBJECTIVES: To determine the source of drinking water and to assess its
      relationship with the frequency of diarrhoea among households of Nurpur Shahan.
      METHODS: A cross-sectional descriptive study was carried out in January 2010 with
      a preformed questionnaire. Systematic random sampling was used to collect data.
      Participants' consent was obtained and confidentiality was maintained during the
      survey and during analysis. Households were evaluated for the frequency of
      diarrhoea in relation to their water source, its purification, and availability
      of sanitation facilities. All collected data was analyzed using SPSS 10.0.
      RESULTS: Of the 107 households surveyed, 2.8% used wells, 63% used tap water and
      32.7% used hand pumps, whereas only 0.9% consumed store-bought water as their
      major source of drinking water. The difference in the frequency of diarrhoea
      between those households who purified their water and those that did not was just
      1%. The relationship between the source of drinking water and the frequency of
      diarrhoea was not statistically significant (p = 0.319). Surprisingly households
      with no disposal facilities only had a 20% frequency of diarrhoea; this was found
      to be statistically significant (p = 0.023). CONCLUSIONS: This study contradicts
      the general conception that water supply is responsible for diarrhoea in the
      locality of Nurpur Shahan; it was found that the statistical difference between
      diarrhoea resulting from purified and non purified water was very small (p
      value=0.587). Rather, improper sanitation and poor personal hygiene seem largely
      responsible for diarrhoea in this rural Islamabad community.

PMID- 22360048
TI  - White coat hypertension is not a benign entity: a cross-sectional study at a
      tertiary care hospital in Pakistan.
AB  - OBJECTIVES: To determine the frequency of White Coat Hypertension in patients
      undergoing ambulatory blood pressure monitoring at a tertiary care center and to
      compare ambulatory blood pressure profiles of normotensives, white coat
      hypertensives and hypertensives. METHODS: A descriptive cross-sectional study was
      conducted which included all adult patients undergoing ambulatory blood pressure
      monitoring over a 3-year period. Those patients with incomplete data, less than
      85% successful BP readings and inadequate number of daytime and nighttime
      readings were excluded from the study. The data on ambulatory blood pressure
      monitoring comprised of demographics, blood pressure, pulse pressure and mean
      arterial pressure readings at every 30 minutes interval and also a graphical
      representation of patients' 24-hour blood pressure recording. SPSS was used for
      data analysis. Chi-square test and analysis of variance (ANOVA) was used for
      qualitative and quantitative variables respectively. RESULTS: A total of 277
      patients with a mean age of 48.98 +/- 17.52 years were included. There were 189
      (58%) males included in the study. Out of the total, 46 (16.6%) patients had
      White Coat Hypertension, 59 (21.3%) were Normotensive and 172 (62.1%) had
      Hypertension. The mean age of Normotensives was 40.80 +/- 14.11 years, White Coat
      Hypertensives was 37.72 +/- 14.58 years and Hypertensives was 54.80 +/- 16.76
      years (p <0.001). The overall average Systolic Blood Pressure in Normotensives
      was 118.69 +/- 6.61mm Hg in White Coat Hypertensives 120.57 +/- 6.71 mmHg and in
      Hypertensives it was 131.18 +/- 13.14mm Hg (p<0.001). The overall systolic load
      in Normotensives was 12.98 +/- 15.21, White Coat Hypertensives 15.86 +/- 14.12
      and Hypertensives 41.71 +/- 28.21 (p value<0.001). The Mean Arterial Pressure in
      Normotensives was 90.17 +/- 5.02 mm Hg, in White Coat Hypertensives 90.17 +/-
      5.08 mmHg and in Hypertensives it was 96.08 +/- 9.21mm Hg (p <0.001). The average
      Pulse Pressure in Normotensives was 43.56 +/- 6.29, White Coat Hypertensives
      46.20 +/- 6.49 and in Hypertensives it was 54.65 +/- 12.86 (p <0.001).
      CONCLUSION: Our study has shown a frequency of White Coat Hypertension, which is
      similar to many populations globally. All parameters of hypertension are more
      prevalent in this group compared to normotensives, which signifies that White
      Coat Hypertension is not a benign entity in our population and it needs to be
      closely followed for development of Hypertension and other cardiovascular
      complications.

PMID- 22360049
TI  - Scalpel safety and new scalpel blade remover.
AB  - Percutaneous injuries to surgical staff carry a reciprocal risk for patients,
      with potential for infection transmission from provider to patient. The operating
      room is the highest-risk setting for this mode of transmission because open
      wounds are susceptible to contamination, and injury to the hands of surgical
      staff resulting in bleeding is not uncommon. The traditional scalpel (surgical
      knife) has been extensively used in surgery for a number of years and would be
      the most widely used surgical instrument in the world at present. A conventional
      surgical scalpel comprises a reusable, sterile handle having a tang at one end on
      which a replaceable slotted blade is mounted. The handle is intended to be used
      repeatedly, but the blade is normally discarded after each instance of use.
      Removal devices are designed to protect the user and downstream staff from
      accidental injury when removing a scalpel blade from a reusable handle. Passing
      tray and single-handed scalpel blade remover. It is a primary object of the
      present invention (Patent No. 62851- 40294) to reduce or substantially eliminate
      the risk of changing scalpel blades. It is a further object of the present
      invention to simplify the removal of a scalpel blade from its handle.

PMID- 22360050
TI  - Mucoepidermoid carcinoma of the base of tongue.
AB  - Mucoepidermoid carcinomas are thought to arise from the reserve cells of salivary
      gland ducts. Minor salivary glands are located all around the oral cavity and
      base of the tongue; however few cases of MEC of the base of the tongue have been
      reported in literature and no guidelines are available for its management. Here
      we would like to present the case of a 71 year old male with mucoepidermoid
      carcinoma of the base of the tongue successfully treated with surgical excision
      and neck dissection. Regular clinical follow up showed no signs of recurrence at
      9 months post excision.

PMID- 22360051
TI  - Patient exploitation.

PMID- 22360052
TI  - Acne and dairy products.

PMID- 22360053
TI  - Medical professionalism and social media: the responsibility of military medical
      personnel.

PMID- 22360054
TI  - A novel application of stellate ganglion block: preliminary observations for the
      treatment of post-traumatic stress disorder.

PMID- 22360055
TI  - Risk factors for medical disability in U.S. enlisted Marines: fiscal years 2001
      to 2009.
AB  - OBJECTIVE: To assess factors associated with medical disability in the U.S.
      Marine Corps. METHODS: Case-control study enrolling 11,554 medical disability
      cases of U.S. enlisted Marines referred to the Physical Evaluation Board fiscal
      year 2001 to 2009 and 42,216 controls frequency matched to cases in a 4:1 ratio
      on year of accession into the service were analyzed utilizing bivariate and
      multivariate logistic regression analysis. RESULTS: Increased age and body mass
      index at accession were associated with higher odds of medical disability.
      Females (odds ratio adjusted [OR(adj)] = 1.3, 95% confidence interval [CI] = 1.2
      1.3) have higher odds of disability than males. "Healthy Warrior Effect" was
      observed in that those who deployed (OR(adj) = 0.48, 95% CI = 0.46-0.50) had
      decreased odds of medical disability than those who did not deploy. Medical
      waivers at accession (OR(adj) = 1.12, 95% CI = 1.01-1.23) increased the odds of
      medical disability. CONCLUSIONS: Continued surveillance of the disability
      evaluation system is needed to help develop preventive measures and to help
      policy makers establish evidence-based policies on accession, deployment, and
      retention standards over the lifecycle of service members.

PMID- 22360056
TI  - Sports medicine training room clinic model for the military.
AB  - A transition from traditional problem-based clinics to the Sports Medicine and
      Reconditioning Team (SMART) clinic model was completed by January 2009 at Marine
      Corps Base Camp Lejeune. The SMART clinic model allows for more patients to be
      seen and enhances coordinated care between providers. The objective of this
      research is to show the advantages of implementing a training room team approach
      for the care of musculoskeletal injuries in active duty members by comparing the
      number of patients seen, the number of limited duty (LIMDU) periods, the number
      of physical evaluation boards (PEBs), and the percentage of orthopedic referrals.
      Electronic medical records for patients seen at sports medicine clinics between
      January 1, 2007 and December 31, 2010 were reviewed. Naval Hospital Camp Lejeune
      provided a database of patients placed on LIMDU and PEB from 2007 through 2010.
      Fifty-eight and twenty-four percent more encounters occurred in 2009 and 2010,
      respectively, than that in 2007. The percentage of LIMDU referred for PEB in 2010
      was reduced to 9% compared to that in 2007. In conclusion, the SMART clinic model
      allows for more patients to be seen and a reduction in the percentage of patients
      recommended for PEB from LIMDU.

PMID- 22360057
TI  - Theoretically-driven infrastructure for supporting health care teams training at
      a military treatment facility.
AB  - Designated a Department of Defense Team Resource Center (TRC) in 2008, Naval
      Medical Center Portsmouth (NMCP) currently hosts three tri-service health care
      teams training courses annually. Each consists of didactic learning coupled with
      simulation-based training exercises to provide an interactive educational
      experience for health care professionals. Simulated cases are developed to
      reinforce specific teamwork skills and behaviors, and to incorporate a variety of
      technologies including standardized patients, manikins, and virtual reality. The
      course is also the foundation of a research program designed to explore
      applications of modeling and simulation for enhanced team training in health
      care. The TRC has adopted two theoretical frameworks for evaluating training
      efficacy and outcomes, and has used these frameworks to guide a systematic
      reconfiguration of the infrastructure supporting health care teams training at
      NMCP.

PMID- 22360058
TI  - An alternative approach to the Army Physical Fitness Test two-mile run using
      critical velocity and isoperformance curves.
AB  - The purpose of this study was to evaluate the use of critical velocity (CV) and
      isoperformance curves as an alternative to the Army Physical Fitness Test (APFT)
      two-mile running test. Seventy-eight men and women (mean +/- SE; age: 22.1 +/-
      0.34 years; VO2(MAX): 46.1 +/- 0.82 mL/kg/min) volunteered to participate in this
      study. A VO2(MAX) test and four treadmill running bouts to exhaustion at varying
      intensities were completed. The relationship between total distance and time-to
      exhaustion was tracked for each exhaustive run to determine CV and anaerobic
      running capacity. A VO2(MAX) prediction equation (Coefficient of determination:
      0.805; Standard error of the estimate: 3.2377 mL/kg/min) was developed using
      these variables. Isoperformance curves were constructed for men and women to
      correspond with two-mile run times from APFT standards. Individual CV and
      anaerobic running capacity values were plotted and compared to isoperformance
      curves for APFT 2-mile run scores. Fifty-four individuals were determined to
      receive passing scores from this assessment. Physiological profiles identified
      from this procedure can be used to assess specific aerobic or anaerobic training
      needs. With the use of time-to-exhaustion as opposed to a time-trial format used
      in the two-mile run test, pacing strategies may be limited. The combination of
      variables from the CV test and isoperformance curves provides an alternative to
      standardized time-trial testing.

PMID- 22360059
TI  - Influence of fatigue and load carriage on mechanical loading during walking.
AB  - Load carriage and muscular fatigue are two major stressors experienced by
      military recruits during basic training. The purpose of this study was to assess
      the influences of load carriage and muscular fatigue on ground reaction forces
      and ground reaction loading rates during walking. Eighteen healthy males
      performed the following tasks in order: unloaded and unfatigued walking, loaded
      and unfatigued walking, fatiguing exercise, loaded and fatigued walking, and
      unloaded and fatigued walking. The fatiguing exercise consisted of a series of
      metered step-ups and heel raises with a 16-kg rucksack. Loaded walking tasks were
      performed with a 32-kg rucksack. Two-way repeated measures analysis of variances
      were used to determine the effects of fatigue and load carriage on ground
      reaction forces and loading rates. Muscular fatigue has a significant influence
      on peak vertical ground reaction force and loading rate (p < 0.01). Load carriage
      has a significant influence on peak ground reaction forces and loading rates (p <
      0.001). As both muscular fatigue and load carriage lead to large increases of
      ground reaction forces and loading rates, the high incidence of lower extremity
      overuse injuries in the military may be associated with muscular fatigue and load
      carriage.

PMID- 22360060
TI  - Blisters on the battlefield: the prevalence of and factors associated with foot
      friction blisters during Operation Iraqi Freedom I.
AB  - BACKGROUND: Foot friction blisters in military personnel lessen a soldier's
      mobility, concentration, and critical decision-making skills. OBJECTIVE: To
      determine the prevalence of and factors associated with friction blisters during
      deployment in all military personnel who nonurgently presented to the 28th Combat
      Support Hospital. METHODS: A cross-sectional survey was performed at the 28th
      Combat Support Hospital. Statistical tests used included descriptive statistics,
      chi-square tests, and logistic regression for nominal data. RESULTS: The response
      rate was 97% with 872 surveys completed. Blister prevalence was 33% (95%
      confidence interval [CI] = 30.0-36.4). Eleven percent of these sought treatment
      (p < 0.001). Factors increasing the risk of developing blisters include female
      sex (prevalence ratio [PR] = 1.55, 95% CI = 1.27-1.91), wearing boots not broken
      in (PR = 1.52, CI = 1.26-1.85), longer than 6 months in theater (PR = 1.33, CI =
      1.09-1.63), and history of prior blisters (PR = 2.08, CI = 1.69-2.56).
      CONCLUSIONS: The prevalence of foot friction blisters was 33% during a 12-month
      block of Operation Iraqi Freedom I. Of these, 11% required medical care. The
      group most likely to develop blisters is women, ages 26 to 34, who are unable to
      break in their boots and have a past history of blisters.

PMID- 22360061
TI  - Visual symptoms and G-induced loss of consciousness in 594 Chinese Air Force
      aircrew--a questionnaire survey.
AB  - A questionnaire survey was performed for the first time to assess the prevalence
      of visual symptoms and G-induced loss of consciousness (G-LOC) due to +Gz
      exposure in the Chinese Air Force (CAF) to determine the effectiveness of current
      G tolerance training. Responses were received from 594 individuals. Among them,
      302 reported at least one episode of some sort of symptoms related to +Gz,
      including 110 (18.5%) with visual blurring, 231 (38.9%) with greyout, 111 (18.7%)
      with blackout, and 49 (8.2%) with G-LOC. Incidences were most common in aircrew
      with 250-1,000 flying hours (53.6%) and were more prevalent in those with fewer
      on type flying hours (p < 0.001). The most common situation was reported between
      +5 and 5.9 Gz. The results indicate a fairly high prevalence of visual symptoms
      and G-LOC among Chinese Air Force aircrew. There remains considerable scope for
      +Gz education, particularly in the early centrifuge training and selection of
      rational physical exercises.

PMID- 22360062
TI  - CT severity spectrum of penetrating eye injuries from blasts.
AB  - Penetrating eye trauma from blasts can result in a vast spectrum of ocular
      injuries. Several cases of orbital trauma are reviewed, all of which occurred
      during combat operations and treated in an Air Force Theater Hospital. Computed
      tomography was used as the primary imaging modality and proved crucial in
      determining the extent of ocular injury. This report focuses on factors we
      believe affect globe salvageability, reviews imaging modalities in theater, and
      briefly discusses management in theater and aeromedical evacuation after initial
      injury.

PMID- 22360063
TI  - Ultrasound triage of ocular blast injury in the military emergency department.
AB  - INTRODUCTION: Ultrasound (US) provides rapid effective assessment of the globe.
      In Afghanistan, ocular blast injuries are common. We present a case series
      demonstrating the value of US in this context. METHODS: 29 patients with
      suspected blast eye injury had both computed tomography (CT) of the head and
      ocular US as part of their standard care in a military hospital in Afghanistan.
      The US images were assessed by blinded consultants (emergency department and
      radiology) and compared with the CT reports. RESULTS: 18 patients had an
      intraocular injury on either CT or US. CT identified 11 injuries. US detected 18,
      including all 11 detected by CT. Inter-rater agreement was high (28/29).
      DISCUSSION: This series suggests that US may be as good as CT at detecting ocular
      blast injuries. However, inability to follow up local national patients meant
      that the clinical relevance of these findings cannot be quantified. US is likely
      to have a role on deployed operations in triaging possible ocular injuries.
      CONCLUSIONS: US is an easy, cheap alternative to CT for the assessment of blast
      injury to the eye. It appears to have identified all injuries detected by CT in
      this series and can be accurately interpreted by emergency physicians.

PMID- 22360064
TI  - The ANAM lacks utility as a diagnostic or screening tool for concussion more than
      10 days following injury.
AB  - Congress has mandated that the Department of Defense perform screening for
      concussion, or mild traumatic brain injury, on all service members redeploying
      from Iraq and Afghanistan. However, the retrospective diagnosis of concussion is
      complicated by the subjective nature of the complaints, overlap of symptoms with
      other conditions, and the normally rapid recovery of neurocognitive function
      following a concussive event. One diagnostic and screening test in current use by
      the Department of Defense is the Automated Neuropsychological Assessment Metrics
      (ANAM). A team of researchers deployed to Iraq between January and April 2009 to
      test the validity of the ANAM for the diagnosis of concussion in the combat
      environment. Performance by concussed participants on all six ANAM subtests was
      compared with that of controls. The ANAM appears to have no utility as an
      individual diagnostic or population screening tool for the detection of
      neurocognitive dysfunction from a single, uncomplicated concussion when
      administered 10 or more days following injury. Further studies are required to
      determine the modalities providing optimal sensitivity and specificity for use as
      diagnostic or screening tests beyond the first 72-hour acute postinjury period.

PMID- 22360065
TI  - The parenting cycle of deployment.
AB  - Parents of dependent children comprise approximately 42% of Active Duty and
      National Guard/Reserve military members serving in Operation Iraqi
      Freedom/Operation Enduring Freedom. Recent estimates indicate that more than two
      million children have experienced parental deployment since the terrorist attacks
      on September 11, 2001. This article seeks to characterize the impact of the
      deployment life cycle on parenting roles among service members and at-home
      partners/caregivers of dependent children. Specifically, a new conceptual
      framework is presented for considering the ways in which parenting and co
      parenting processes are affected by the demands and transitions inherent in
      contemporary deployment to a war zone. Although the phase-based emotional cycle
      of deployment continues to offer an instructive description of the broad
      challenges faced by military couples, a parenting cycle of deployment model
      shifts the perspective to the critical and largely ignored processes of parenting
      in the context of deployment and war, and to the realities faced by parents
      serving in the U.S. military. Implications for prevention, intervention, and
      future research related to military families are addressed.

PMID- 22360066
TI  - Problems with veteran-family communication during operation enduring
      freedom/operation Iraqi freedom military deployment.
AB  - Twenty Reserve component (Army and Marines) and Army National Guard male veterans
      of Operational Enduring Freedom/Operation Iraqi Freedom discuss their deployment
      and postdeployment family reintegration experiences. A Grounded Theory approach
      is used to highlight some of the ways in which family miscommunication during
      deployment can occur. Communication with civilian family members is affected by
      the needs of operational security, technical problems with communication tools,
      miscommunication between family members, or because veterans have "nothing new to
      say" to family back home. These communication difficulties may lead to an initial
      gulf of understanding between veterans and family members that can cause family
      strain during postdeployment family reintegration. We end with a discussion of
      veteran family reintegration difficulties.

PMID- 22360067
TI  - Veteran status and alcohol use in men in the United States.
AB  - OBJECTIVE: This study sought to compare patterns of alcohol use between male
      veterans and nonveterans. METHODS: Data came from the 2004 Behavioral Risk Factor
      Surveillance System, a U.S. national telephone survey using stratified random
      sampling. Outcomes were 30-day alcohol use, binge drinking (5+ drinks on one
      occasion), and heavy drinking (2+ drinks per day). Age-stratified weighted
      regression analyses compared men who were veterans (n = 36,874) to those who were
      not (n = 77,056), and veterans who used Veterans Health Administration (VHA)
      services in the past year (n = 7,606) to veterans who did not, adjusting for
      potential confounders. RESULTS: Veterans aged 41 to 60 were less likely to binge
      drink (adjusted odds ratio [AOR] = 0.8) and veterans aged 61 to 70 were more
      likely to drink heavily compared to same-age men without military experience (AOR
      = 1.7). There were no significant differences in binge or heavy drinking for
      other age groups. Among veterans aged 51 to 60, those who used VHA services were
      more likely to report binge drinking than those who did not (AOR = 1.4).
      CONCLUSIONS: Male veterans generally have similar patterns of alcohol use as men
      without a history of military service, but the elevated alcohol use of specific
      groups of veterans merits concern.

PMID- 22360068
TI  - The need for reform of human subjects protections in military health research.
AB  - A number of factors currently hinder the ability of researchers to conduct
      military-funded research studies successfully in a timely fashion, including low
      risk, psychosocial and behavioral, multisite studies. Our experiences and a
      review of the literature highlight examples of delays and wide variations in
      military and civilian Institutional Review Board (IRB) approvals. This article
      describes the specific experiences from a program of research over a 15-year
      period, required documents unrelated to protection of human subjects, onsite
      study principal investigators, examples from other research, and participant
      recruitment. Concern is raised about significant resources committed to nonstudy
      interventions, some described as "training," which fall outside of IRB review and
      its human subject protections. A broad initiative for evidenced-based research,
      particularly psychosocial and behavioral research, could become marginalized with
      limited resources redirected to technology-focused quick fixes and data
      collection during training. Possible solutions and initiatives are proposed that
      emphasize the need to reform IRB oversight and associated paperwork that is
      required to undertake military research.

PMID- 22360069
TI  - Good interventions that few use: uptake of insect bite precautions in a group of
      Canadian Forces personnel deployed to Kabul, Afghanistan.
AB  - We evaluated use of interventions to prevent insect bites in Canadian personnel
      deployed to Kabul, Afghanistan. Data were collected through a self-report written
      survey. The response rate was 92%, and intervention uptake was 11% applied
      repellent that day, 21% slept under a bednet their last sleep, and 78% wore
      insecticide-treated clothing. Two associations were usually evident in
      multivariate analyses: persons perceiving risk of exposure as high were more
      likely to use bednets and repellent, and individuals reminded to use an
      intervention had higher odds of doing so. However, even if perception of exposure
      risk was high and reminders were received, the use of bednets (60%) and repellent
      (40%) was relatively low. Hence, on the one hand, increased uptake of
      interventions through targeted messaging might be possible. On the other hand,
      effectiveness of these interventions might be substantially constrained because
      of nonuse, even in a motivated and informed population.

PMID- 22360070
TI  - Development of hydrolysis probe-based real-time PCR for identification of
      virulent gene targets of Burkholderia pseudomallei and B. mallei--a retrospective
      study on archival cases of service members with melioidosis and glanders.
AB  - Burkholderia pseudomallei and B. mallei are two highly pathogenic bacteria
      responsible for melioidosis and glanders, respectively. Our laboratory developed
      hydrolysis probe-based real-time polymerase chain reaction assays targeting type
      three secretion system (TTS) and transposase family protein (TFP) of B.
      pseudomallei and B. malli, respectively. The assays were validated for target
      specificity, amplification sensitivity, and reproducibility. A bacterial DNA
      panel, composed of B. pseudomallei (13 strains), B. mallei (11 strains),
      Burkholderia species close neighbors (5 strains), and other bacterial species (17
      strains), was prepared for specificity testing. Reference DNAs from B.
      pseudomallei and B. mallei bacterial cultures were used as controls for
      amplification, limit of detection, and reproducibility testing. The two TaqMan
      assays, Bp-TTS 1 and Bm-TFP, were optimized and applied in a retrospective study
      of archived cases from the Armed Forces Institute of Pathology. We tested 10
      formalin-fixed paraffin-embedded blocks originally from autopsy specimens of
      patients who died of melioidosis or glanders during or after overseas tours in
      1960s. Polymerase chain reaction results confirmed that DNA samples from formalin
      fixed paraffin-embedded blocks of eight patients with melioidosis were positive
      for Bp-TTS 1 target and two patients with glanders were positive for Bm-TFP
      target.

PMID- 22360071
TI  - Fluid resuscitation using the intraosseous route: infusion with lactated Ringer's
      and hetastarch.
AB  - OBJECTIVE: The effectiveness of the intraosseous (IO) route for fluid
      resuscitation remains uncertain. This study compares IO infusion rates and
      estimated volume expansion using clinically relevant infusion pressures with
      lactated Ringer's (LR) and hetastarch (HES). METHODS: IO needles were placed in
      the sternum or tibia for infusion of HES and LR in 8 Yorkshire pigs. Pressures
      were recorded at variable flow rates and linear regression used to identify flow
      rates at 100 and 400 mm Hg. Volume expansion was calculated for a 10-minute
      infusion. RESULTS: Mean LR flow rates (mL x min(-1)) were 24/111 (tibia--100/400
      mm Hg) and 8/34 (sternum--100/400 mm Hg). The HES flow rates (mL x min(-1)) of
      10/44 (tibia--100/400 mm Hg) and 6/26 (sternum--100/400 mm Hg) were significantly
      lower or -40% (p < 0.01) of the LR flow rates into the tibia and -70% (p < 0.05)
      into the sternum. Mean volume expansion (mL) for a 10-min infusion of LR was
      estimated to be 80/369 (tibia--100/400 mm Hg) and 27/112 (sternum--100/400 mm
      Hg). In comparison, HES volume expansion was -20% higher for the tibia (p > 0.05)
      and 110% to 120% higher for the sternum (p < 0.05). CONCLUSION: HES flow rates
      are lower than LR flow rates in the sternum and tibia of swine. Sternal infusion
      of HES is likely to provide greater estimated intravascular volume expansion than
      LR despite the lower infusion rates.

PMID- 22360072
TI  - Breastfeeding practices in military families: a 12-month prospective population
      based study in the national capital region.
AB  - Breastfeeding practices in military families have not been widely investigated.
      The objective of this study was to measure the prevalence and duration of
      breastfeeding among uniformed families and identify factors associated with
      breastfeeding. We conducted a prospective study of 253 mothers of new infants
      from July to December 2004. Initial information gathered included demographic
      data, feeding choices, and intended duration of breastfeeding. Follow-up surveys
      were conducted until 12 months postpartum. 51% of mothers were breastfeeding at 6
      months and 25% at 1 year. Mothers on active duty were equally likely to
      breastfeed than non-active duty mothers. Officer mothers were 3 times more likely
      to breastfeed compared to enlisted mothers (p = 0.005). Mothers with higher
      education were twice as likely to breastfeed longer (p = 0.015). Families
      participating in Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) were 2.5 times less likely to breastfed at 1 year (p < 0.001). Our
      study shows a higher percentage of women initiating and maintaining breastfeeding
      compared to national data, but still less than current American Academy of
      Pediatrics guidelines. Our study suggests that to improve breastfeeding rates
      among uniformed families, more attention may need to be directed to younger,
      enlisted mothers and those families in a lower socioeconomic status or receiving
      WIC assistance.

PMID- 22360073
TI  - Knowledge, opinions, and practices of infant sleep position among parents.
AB  - This study's objective was to assess the knowledge, opinions, and practices of
      infants' sleep positions and their association with demographics. A cross
      sectional descriptive design was used to survey a convenience sample of military
      beneficiary parents being seen at a military treatment facility in the United
      States. A 19-item investigator-designed questionnaire was adapted using the "Safe
      Sleep Survey" developed by Indiana Perinatal Network. A sample of 161 parents
      responded. Forty percent were fully aware of the safe sleep facts for infants;
      85% believed supine position was the safest; and 69% of those who believed supine
      position to be the safest also practiced their belief. Major reasons for
      nonsupine sleeping positions were for infant preference, comfort, and fear of
      choking; whereas supine position was for safety reasons. Parents' opinions of
      safe position and their practices (p < 0.001) were significantly associated,
      whereas knowledge on infant safe sleep facts (p = 0.611) was not. The results
      indicate that there is still a need for education. However, merely providing
      information to increase knowledge alone is not enough to change behavior, as
      attitude was an important factor for the behavior. Theory-based intervention
      associated with change in behavior will have an impact on parents' attitudes.

PMID- 22360075
TI  - Swallowed by the dragon.

PMID- 22360074
TI  - An unusual presentation of inflammatory bowel disease.
AB  - Erythema nodosum (EN) is an infrequent but well-described extraintestinal
      manifestation of inflammatory bowel disease (IBD). We report a case of a
      previously healthy 8-year-old girl who presented to her primary care manager with
      a chief complaint of EN and was later found to have Crohn's disease. This article
      reviews the causes of EN, the significance of EN in IBD, and the recommended
      diagnostic approach to IBD in children.

PMID- 22360076
TI  - Correction of a severely rotated maxillary central incisor with the Whip device.
AB  - The following case report presents an appliance named Whip device used for the
      correction of severe rotations of anterior teeth in pre-adolescent patient. A 9
      year-old boy with a severe 90 degrees rotation of upper left central incisor was
      treated with a Whip appliance. After 3 months of treatment, the position of the
      upper left central incisor was orthodontically corrected.

PMID- 22360077
TI  - The treatment of an impacted mandibular canine: case report.
AB  - The treatment of a patient with an impacted lower canine. After surgical exposure
      of the tooth, extrusion was performed with a removable appliance and followed by
      fixed orthodontics. In radiographic assessment, no resorption was observed either
      on canine or on the neighboring premolar root.

PMID- 22360078
TI  - Emergency orthodontic care.
AB  - Orthodontic appliances or parts of orthodontic appliances have caused problems
      from less severe like discomfort, ulcers and irritation of lips or cheeks to most
      severe problems like swallowing or aspiration of appliances or its parts. The
      type of appliances that have caused problems and their clinical management are
      discussed. Suggestions are made to try and avoid the problems that were
      encountered in the literature in patients undergoing orthodontic treatment.

PMID- 22360079
TI  - Assessing skeletal relationships using the cervical vertebral curvature.
AB  - The aim of this study was to determine any association amongst the cervical
      vertebral morphology and the various sagittal and vertical facial patterns. The
      results of this study demonstrate a relationship between the cervical vertebral
      morphology and the skeletal facial patterns. This may be of some assistance to an
      orthodontist to diagnose a skeletal malocclusion at a glance just by looking at
      the patient's cervical vertebral curvature.

PMID- 22360080
TI  - Is lower incisor inclination a good parameter to estimate alveolar bone level? A
      cone-beam CT evaluation.
AB  - This study verified whether an IMPA above the normative value could be a sign of
      reduced lower incisor labial bone height. Such association, which could improve
      the quality of treatment planning, was not confirmed. A cone-beam CT is still
      recommended when a more precise diagnosis is needed.

PMID- 22360081
TI  - Early treatment of class III malocclusion with Petit facemask therapy.
AB  - Class III malocclusion with retrusive maxilla can be orthopedically corrected in
      the deciduous or mixed dentition, with reverse pull headgear in combination with
      or without rapid maxillary expansion. The advantage of expansion in these
      patients is to correct the posterior cross bite, and disarticulate the maxilla.
      This is a case report of successful treatment of developing skeletal class III
      malocclusion using Petit facemask without maxillary expansion. A 10-year-old girl
      presented with concave facial profile and decreased lower facial height. She had
      bilateral class III molar and canine relationships with reverse overjet of 3 mm
      and over bite of 6 mm. The treatment objective was to correct the skeletal class
      III to achieve a more harmonious facial profile. Patient was treated with Petit
      facemask, by applying a force directed at angle of 30 degrees to occlusal plane
      for a period of 4 months. The intra-oral appliance used was an acrylic cap splint
      without expansion. The post treatment results showed a significant improvement in
      facial profile with class I molar relationship and no change in treatment time
      when compared with patients treated by facemask therapy and maxillary expansion.

PMID- 22360082
TI  - Guiding atypical facial growth back to normal. Part 1: Understanding facial
      growth.
AB  - Many practitioners find the complexity of facial growth overwhelming and thus
      merely observe and accept the clinical features of atypical growth and do not
      comprehend the long-term consequences. Facial growth and development is a
      strictly controlled biological process. Normal growth involves ongoing bone
      remodeling and positional displacement. Atypical growth begins when this
      biological balance is disturbed With the understanding of these processes,
      clinicians can adequately assess patients and determine the causes of these
      atypical facial growth patterns and design effective treatment plans. This is the
      first of a series of articles which addresses normal facial growth, atypical
      facial growth, patient assessment, causes of atypical facial growth, and guiding
      facial growth back to normal.

PMID- 22360083
TI  - Stainless hooks to bond lower lingual retainer.
AB  - We introduced a simple and economical technique for precise placement of lower
      lingual retainers. Two stainless steel hooks made of 0.6mm wire are placed
      interdentally in the embrasure area between canine and lateral incisor
      bilaterally to lock the retainer wire in the correct position. Etch, rinse and
      dry the enamel surfaces with the retainer passively in place, then bond the
      retainer with light-cured adhesive. Hooks are simple to fabricate and eliminate
      the need for a transfer tray.

PMID- 22360084
TI  - A modified uprighting spring for use in edgewise system.
AB  - One of the most powerful mechanics for 2nd order correction is uprighting spring.
      Unfortunately, the vertical tube for inserting the uprighting spring is not
      included in the majority of commercially available edgewise bracket systems. This
      article presents a simple method for inserting the uprighting spring in the
      horizontal slot of the bracket.

PMID- 22360085
TI  - Case finishing: is it all about bracket prescription?

PMID- 22360086
TI  - Why straight teeth?

PMID- 22360087
TI  - Social media & you.

PMID- 22360089
TI  - Action on staff sickness needed as NHS fails to meet reduction target.

PMID- 22360088
TI  - Staff sickness requires a balanced approach.

PMID- 22360090
TI  - Learn from Mid Staffs and set safe staffing levels, say patients.

PMID- 22360091
TI  - Call for clearer picture of patient health on admission to hospital.

PMID- 22360092
TI  - It's not all bad news: how the Care campaign challenges are being met.

PMID- 22360093
TI  - Health on the inside.
AB  - Prison nurses at HMP High Down in Surrey have recruited healthcare
      representatives from the inmates to improve uptake of screening and vaccinations.
      The scheme has boosted representatives' confidence and developed skills they hope
      to use after they are released.

PMID- 22360094
TI  - Constrained by impossible ideals.
AB  - The nursing profession is rife with impossible ideals that nurses struggle to
      reconcile, argues the author. The result is a widespread sense of victimisation
      and powerlessness.

PMID- 22360095
TI  - Environmental health.
AB  - A nurse-led project to improve the physical environment of the dementia unit at
      King's College Hospital is almost complete. Even small changes in design and
      decor have made a huge difference to patients and staff.

PMID- 22360096
TI  - An introduction to diagnosis and management of headache.
AB  - Headache is a common, painful event that can be acute and/or chronic in nature.
      This article aims to give readers an insight into the condition by covering
      issues related to classification, diagnosis and management. The article
      highlights the importance of establishing whether headache is a secondary symptom
      of another disease process or a primary condition. Classification of headache and
      effective history taking are essential to this process. Headache associated with
      withdrawal from pain medication is also discussed. The different management
      strategies available, and how chronic conditions are best treated in a specialist
      centre, are considered. The goal of headache management is for patients and
      healthcare professionals to work together to minimise pain and improve quality of
      life.

PMID- 22360097
TI  - An alternative treatment approach to mitral regurgitation.
AB  - This article aims to increase knowledge and understanding of mitral valve
      regurgitation to assist nurses in providing effective patient care and support
      the treatment options available. It focuses on the MitraClip, a procedure to
      repair the mitral valve using a percutaneous approach.

PMID- 22360098
TI  - An overview of cardiovascular disease risk assessment.
AB  - Cardiovascular disease (CVD) risk assessment is being undertaken in the UK as a
      result of a national drive to reduce premature mortality and the economic burden
      of vascular disease. This article focuses on ways in which primary care teams can
      implement a systematic approach to CVD risk assessment. A systematic approach to
      CVD risk assessment includes identification of the target population, the
      collection of information and data to calculate a CVD risk score, and management
      of the results. Primary care teams can work successfully with lifestyle teams and
      public health to provide a comprehensive service.

PMID- 22360099
TI  - Mental health in older people.

PMID- 22360100
TI  - University challenge.

PMID- 22360101
TI  - Looking at the bigger picture.

PMID- 22360102
TI  - A divine set of skills.

PMID- 22360103
TI  - The gift of giving: nurse philanthropy.

PMID- 22360104
TI  - The relationship of the hospital-acquired injurious fall rates with the quality
      profile of a hospital's care delivery and nursing staff patterns.
AB  - Fall occurrence during hospital stays is a well-recognized nursing-sensitive
      outcome indicator. This study was intended to determine the unique contributions
      of three inpatient satisfaction measures on the hospital-acquired injurious fall
      rates. Study results demonstrated the higher the inpatient satisfaction levels
      with the quietness of hospital environment, the lower the injurious fall rates.
      The physical environment (quietness) of the acute inpatient care settings was a
      significant and meaningful determinant of the prevalence of injurious falls.
      Additionally, more total nursing personnel FTEs per 1,000 discharges and a higher
      percentage of RN FTEs by total nursing personnel FTEs would not result in better
      patient outcomes.

PMID- 22360105
TI  - Internationally educated nurse hiring: geographic distribution, community, and
      hospital characteristics.
AB  - As the largest importer of internationally educated nurses (IENs), the United
      States is considered to be the epicenter of global nurse migration. The purposes
      of this study were to examine the geographic distribution of IEN hiring and
      determine associations between community and hospital characteristics and IEN
      hiring. More community characteristics than hospital characteristics were
      strongly associated with IEN hiring which suggest perceived community needs and
      receptivity to lENs could be an important consideration in hospital
      administrators' decisions to hire IENs. These findings suggest that as the U.S.
      population ages and becomes increasingly diverse, the demand for IENs is likely
      to grow. Nurse leaders and faculty may face challenges with regard to the ethical
      recruitment of IENs from low-income countries, incorporation of IENs into U.S.
      health care organizations, and continued development of a diverse U.S.-educated
      nursing workforce. This study expands understanding of the demand side of IEN
      employment in U.S. hospitals by providing the first in-depth examination of the
      community and hospital factors related to hospitals' IEN hiring.

PMID- 22360106
TI  - Estimating the time involved in managing the 'unoccupied bed:' a time and motion
      study.
AB  - Occupied bed days are often used as a demand indicator when calculating the
      number of nurses required to provide safe care. However, such calculations fail
      to take into account the amount of nursing time consumed by the "unoccupied bed."
      This study used direct observation time-and-motion methods to estimate the time
      and costs associated with a bed that is unoccupied. The average time taken to
      complete all of the activities associated with a bed that was unoccupied due to
      an internal transfer was 8.65 minutes, for a patient discharge 26.27 minutes, and
      for a patient admission 37.7 minutes. An average daily cost for activities
      surrounding these patient movements was approximately $386/day (AUD) in
      registered/enrolled nursing salaries alone. The unoccupied bed is not resource
      neutral and time associated with its maintenance should be considered when
      calculating nursing requirements to provide safe care.

PMID- 22360107
TI  - Crisis management: the activities of nurse managers in Turkey.
AB  - Crisis management is the process of preventing the organization from getting into
      a crisis and taking the organization out of the situation with minimum costs and
      losses in sudden crisis situations. A descriptive study design was used to
      determine the activities of nurse managers regarding crisis management. The most
      common type of crisis encountered at hospitals was natural disasters such as
      earthquakes. To cope with stress regarding crises, 71.6% of nurse managers stated
      they leave the resolution of crises to the top management, 64.7% noted they
      increase the number of the staff members, and 58.1% said they ignore crises. It
      was concluded nurse managers were partially prepared for crises or crisis
      management. Activities of nurse managers for more efficient crisis management in
      hospitals can be restructured according to the results and suggestions of the
      research. Crises can be coped with, turned into opportunities, and negative
      effects of crises can be minimized.

PMID- 22360108
TI  - Making the most of the recession.

PMID- 22360109
TI  - Evolving career paths.

PMID- 22360110
TI  - Health care reform: current updates and future initiatives for ambulatory care
      nursing.
AB  - While the signing of the Patient Protection and Affordable Care Act was a
      historical event marking the beginning of health care reform in the United
      States, it signaled the start of a golden age for ambulatory care nursing.
      Ambulatory care RNs are well-positioned to fully participate in health care
      reform initiatives. RNs are well-positioned to lead, facilitate, and/or
      participate in all patient care medical homes' and accountable care
      organizations' quality and safety initiatives through enhanced use of major
      ambulatory care RN role dimensions such as advocacy, telehealth, patient
      education, care coordination and transitional care, and community outreach. RNs
      are also well-positioned to provide patient-centered care, coordinate care, and
      manage transitions across ambulatory care settings. For the golden age of
      ambulatory care nursing to become a reality, initiatives surrounding
      competencies, education modules, and leadership must be addressed immediately.

PMID- 22360111
TI  - The importance of philanthropy in nursing: an interview with Darlene Curley, MS,
      RN. Interview by Donna M Nickitas.

PMID- 22360112
TI  - Engaging patients and families in ehealth.
AB  - National Health IT Week, which ran from September 11-16, 2011, served as a time
      to highlight the importance of efficient information systems that protect the
      privacy and security of personal health information while improving the delivery
      of health care in the United States. During the week, the health IT community
      came together to raise national awareness regarding the consistent breakthroughs
      and hard work industry professionals, providers, and consumers have put forward
      to ensure they are moving toward the common goal of advancing the future of
      health care through private and secure health IT. Two events during the week (the
      Consumer Health IT Summit and the launch of the HealthlT.gov web site) brought
      home a theme increasingly seen as important to improving our health care system-
      patients participation in their care. Nurses will need to work with patients so
      they understand the importance of their participation as a partner in their care,
      instead of playing a passive role. One way we can do that is to encourage our
      patients to actively use technology to manage their own health care and to share
      information with their health care providers.

PMID- 22360113
TI  - Impact of social media on dental practices.

PMID- 22360114
TI  - Paul Feuerstein, DMD, discusses the newest trends in technology for 2012.

PMID- 22360115
TI  - Anton Woolf, Argen Corporation.

PMID- 22360116
TI  - Implant cementation: clinical problems and solutions.

PMID- 22360117
TI  - Aesthetic denture rehabilitation.

PMID- 22360118
TI  - Canal preparation: single-file shaping technique.

PMID- 22360119
TI  - Bioceramics, part I: the clinician's viewpoint.

PMID- 22360120
TI  - "The simplified concept": predictable posterior composites.

PMID- 22360121
TI  - Conservative contact repairs for patients.

PMID- 22360122
TI  - Achieving natural aesthetics in Class IV restorations.

PMID- 22360123
TI  - Conquering a difficult case.

PMID- 22360124
TI  - An alternative approach to cosmetic space closure.

PMID- 22360125
TI  - A better quality of life with implant-retained overdentures.

PMID- 22360126
TI  - Uncovering the tooth: the diode laser to uncover teeth, brackets and implants.

PMID- 22360127
TI  - ACCEPTED: final revisions to telemedicine standards.

PMID- 22360128
TI  - Leadership standard clarified to address behaviors that undermine a safety
      culture.

PMID- 22360129
TI  - Revisions to 2012 decision rules for Contingent Accreditation. Changes cover
      fraud and abuse and organizations new to accreditation.

PMID- 22360130
TI  - APPROVED: updated medication selection criteria for hospitals.

PMID- 22360131
TI  - Standards changes in response to California law for organizations performing CT
      scans. Revisions effective July 2012.

PMID- 22360132
TI  - Joint Commission promotes improved, patient-centered care for LGBT patients.

PMID- 22360133
TI  - Sensitization profiles in polysensitized patients from a restricted geographical
      area: further lessons from multiplexed component resolved diagnosis.
AB  - BACKGROUND: The micro-array techniques for the detection of specific IgE has
      improved the diagnostic procedures for allergic diseases. This method also allows
      to define sensitisation profiles from an epidemiological point of view. We
      studied the sensitisation pattern in a population of polysensitized patients with
      respiratory allergy, living in a restricted geographical area in the north-west
      Italy. METHODS: Consecutive patients with asthma/rhinitis, living in the province
      of Cuneo, and having at least two positive skin prick test for non related
      aeroallergens were studied by a microarray (Phadia, Milan Italy) which allowed to
      detect specific IgE against 103 different allergen components. RESULTS: The 70
      patients included had specific IgE towards a mean of 4.3 allergens/patient (range
      2-12 allergens). Concerning pollens, 63 (90%) had specific IgE to at least one
      genuine grass pollen allergen, 32 (45.7%) had Ole e 1 specific IgE antibodies,
      although olive tree is not present in the area. A relevant percentage of
      sensitisation to mite was found (47,1%). True co-sensitisation to grass-pollen
      allergens/Bet v 1/Ole e 1 was observed in 15 individuals (21.4%). Prup 1,
      resulted to be a sensitising allergen in 23 patients (32.85%), 4 of whom were co
      sensitised to Prup 3 and/or Art v 3. CONCLUSION: A detailed knowledge of the
      sensitisation pattern may have relevant implications for the prescription of
      specific immunotherapy. Moreover, sensitisation to PR-10 (or profilin),
      frequently associated to oral allergy syndrome, in some cases could hide the
      sensitisation to LTPs which are clinically more relevant.

PMID- 22360134
TI  - Efficacy and safety of sublingual immunotherapy with grass monomeric allergoid:
      comparison between two different treatment regimens.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid
      proved to be well tolerated, safe and effective in patients with respiratory
      allergy. Standard administration regimens are expected to require a long time
      before clinical benefit can be appreciated. We investigated whether pre-seasonal
      and perennial regimens differently affect the clinical efficacy of grass pollen
      SLIT. METHODS: Adult patients with allergic rhino-conjunctivitis with/without
      mild intermittent asthma due to grass pollen were included into this open
      prospective study and randomised to receive SLIT with a continuous regimen (Group
      1: 1,000 AU/week for the entire study period) or a pre-seasonal regimen (Group 2:
      5,000 AU/week for 10 weeks/year for 2 years), or on demand drug therapy alone
      (Group 3) for two years. At entry (November 2005), at the end of the first and
      second pollen season, a Visual Analogue Scale (VAS) was used to assess patients'
      well-being. Symptom score and drug consumption were evaluated during the seasons.
      Methacholine challenge was performed at study entry and conclusion. Adverse
      events were recorded along the whole study duration. RESULTS: Thirty-two patients
      were divided into Group 1 (n = 10), Group 2 (n = 11) and Group 3 (n = 11). A
      significant VAS improvement was observed in both SLIT groups, after the first and
      second pollen season, compared to baseline and to Group 3 (p < 0.05). Less
      symptoms and need for medications resulted during the second season (p < 0.05).
      No relevant variations in bronchial hyper-reactivity have been observed between
      the three groups. Only 2 patients experienced local or mild reactions in SLIT
      groups. CONCLUSION: Both pre-seasonal and continuous regimen of SLIT with
      monomeric allergoid turned out effective and safe, suggesting that a pre-seasonal
      course with 5,000 AU/week for 10 weeks may represent a convenient option in
      patients with grass pollen allergic rhinitis with/without mild intermittent
      asthma. Further research is urgently needed to consolidate these preliminary
      evidences.

PMID- 22360135
TI  - Are anti-Phl p 12 IgE levels predictive of oral allergy syndrome in profilin
      hypersensitive patients?
AB  - BACKGROUND: In birch pollen-allergic patients the occurrence of clinically
      relevant crossreactivity to plant-derived foods is clearly related with the level
      of birch-specific IgE. In profilin-hypersensitive patients this has not been
      investigated so far. OBJECTIVE: To investigate whether the levels of profilin IgE
      are predictive of the development of food allergy in hypersensitive patients.
      METHODS: IgE specific for Phl p 12, the grass pollen profilin, were measured in
      37 subjects monosensitized to profilin with (n = 11) or without (n = 26) oral
      allergy syndrome (OAS) following the ingestion of plant-derived foods. RESULTS:
      Patients without a history of OAS showed higher levels of IgE specific for Phl p
      12 than patients with OAS (median 4.74 [range 0.7-41.6] KU/L vs 2.14 [range 0.32
      10.2] KU/L, respectively) although the difference did not reach statistical
      significance (p = 0.07). CONCLUSION: Factors causing the onset of OAS in profilin
      hypersensitive patients remain presently unclear.

PMID- 22360136
TI  - The Piemonte Regional Allergy Network: a model of healthcare organization.
AB  - The Allergology Hospital Network and Regional Register for Severe Allergic
      Reactions (Regional Observatory) is the Piemonte Health Authority new challenge.
      It satisfied the need to promote and monitor the best practice among a variegated
      pool of specialists and to define both state of the art and evolution of
      efficiency and efficacy of standard working process. Harmonization in clinical
      daily activities and report of severe allergic reactions notified to Regional
      Observatory, had been gained by mean of a customized Information Technology (IT)
      solution. The overall target is to ensure a correct diagnostic treatment to
      patients with severe allergic reactions preventing possible future reactions.
      Statistics data as a whole, provide basilar epidemiological information to
      allocate both economical and human resources and to fulfill the rising of health
      diseases. Piemonte Allergology Medical Network with the Regional Register are an
      Italian unique and innovative project. It would represent a benchmark for other
      medical branches.

PMID- 22360137
TI  - Molecular allergology in practice: an unusual case of LTP allergy.
AB  - The authors describe an unusual case of LTP allergy. A 35 years old patient
      presented repeated episodes of angiooedema after food intake and complained 10
      years ago of contact urticaria and rhinoconjunctivitis when exposed to cannabis
      leaves and to marijuana smoke. The suspected responsible foods, such as wheat
      flour in bread, are known to contain LTR Oral syndrome occurred after ingestion
      of walnuts. Cutaneous tests confirmed immediate responses to several flours and
      nuts and also to cannabis leaf and flower. A few months later he had similar
      accidents following peach ingestion and drinking of beer and several wines which
      all induced positive skin tests. Serological investigations using ImmunoCAP and
      ISAC microarray confirmed IgE positivity for n Pru p3, r Cor a 8 and n Art v3. It
      was assumed that sensitization to LTP, the major allergen of cannabis, was
      responsible of the primary sensitization and induced further LTP food allergies.

PMID- 22360138
TI  - Transfer of IgE-mediated hypersensitivity with autologous stem cell
      transplantation.
AB  - In this paper, the transfer of IgE-mediated food allergy by means of autologous
      stem cell transplantation in a 24-years old male patient is reported.

PMID- 22360139
TI  - Determination of secondary structure populations in disordered states of proteins
      using nuclear magnetic resonance chemical shifts.
AB  - One of the major open challenges in structural biology is to achieve effective
      descriptions of disordered states of proteins. This problem is difficult because
      these states are conformationally highly heterogeneous and cannot be represented
      as single structures, and therefore it is necessary to characterize their
      conformational properties in terms of probability distributions. Here we show
      that it is possible to obtain highly quantitative information about particularly
      important types of probability distributions, the populations of secondary
      structure elements (alpha-helix, beta-strand, random coil, and polyproline II),
      by using the information provided by backbone chemical shifts. The application of
      this approach to mammalian prions indicates that for these proteins a key role in
      molecular recognition is played by disordered regions characterized by highly
      conserved polyproline II populations. We also determine the secondary structure
      populations of a range of other disordered proteins that are medically relevant,
      including p53, alpha-synuclein, and the Abeta peptide, as well as an oligomeric
      form of alphaB-crystallin. Because chemical shifts are the nuclear magnetic
      resonance parameters that can be measured under the widest variety of conditions,
      our approach can be used to obtain detailed information about secondary structure
      populations for a vast range of different protein states.

PMID- 22360140
TI  - Experience of aging in patients with rheumatic disease: a comparison with the
      general population.
AB  - OBJECTIVES: Self-perceptions of aging have been shown to predict mental and
      physical health and even longevity. This study examined the aging perceptions of
      patients with rheumatic disease and compared them with the general Dutch
      population. METHODS: Consecutive patients visiting a rheumatology clinic
      completed the Personal Experience of Aging Scale (PEAS) subscales: physical
      decline, social loss, continuous growth, and two sentence stems from the SELE
      instrument (What I like/do not like about getting older ...) as qualitative
      measures of the subjective experience of aging. A representative sample from the
      general Dutch population between 40 and 85 years was used as a comparison group.
      Participants included in this study were 208 patients with a rheumatic disease
      and 975 persons from the Dutch Aging Survey (DAS). RESULTS: Both quantitative and
      qualitative data showed that patients perceived aging more strongly as physical
      decline. These negative experiences did not extend to social and psychological
      domains of aging. Age-group comparisons revealed that patients in middle
      adulthood experienced physical aging similar to older people without a rheumatic
      disease. CONCLUSION: The negative experience of aging in patients is limited to
      the physical domain and does not extend to other domains of life. The negative
      experience of physical aging even in middle-aged groups warrants further studies
      on its effects on mental and physical health outcomes and health behavior in
      patients with rheumatic disease.

PMID- 22360141
TI  - Flexible, all-organic chemiresistor for detecting chemically aggressive vapors.
AB  - Chemiresistors made of thin films of single-walled carbon nanotube (CNT) bundles
      on cellulosics (paper and cloth) can detect aggressive oxidizing vapors such as
      nitrogen dioxide and chlorine at 250 and 500 ppb, respectively, at room
      temperature in ambient air without the aid of a vapor concentrator. Inkjet
      printed films of CNTs on 100% acid-free paper are significantly more robust than
      dip-coated films on plastic substrates. Performance attributes include low sensor
      to-sensor variation, spontaneous signal recovery, negligible baseline drift, and
      the ability to bend the sensors to a crease without loss of sensor performance.

PMID- 22360142
TI  - Molecular characterisation of the causative agents of Cryptococcosis in patients
      of a tertiary healthcare facility in the state of Amazonas-Brazil.
AB  - As there are four major molecular types of Cryptococcus neoformans (VNI, VNII,
      VNIII and VNIV) and four molecular types of Cryptococcus gattii (VGI, VGII, VGIII
      and VGIV), it is important to identify the specific groups causing cryptococcosis
      in different geographical regions. Here, we investigated the molecular types of
      57 cryptococcal isolates from patients in a tertiary care hospital in the state
      of Amazonas, Brazil, between 2006 and 2010. The isolates were characterised by
      PCR fingerprinting using the M13 minisatellite and confirmed by URA5-RFLP
      analysis, and the presence of specific genes from the mating type locus (MATalpha
      and MATa) of these species was analysed by PCR. Most of the patients were male
      (66.7%), between 16 and 30 years of age (51.7%), and HIV-positive (75.0%). Most
      isolates were collected from cerebrospinal fluid samples (71.7%). Most of the C.
      neoformans isolates (n=40) were characterised as members of the VNI molecular
      group (n=39), a unique isolate was characterised as VNII whereas all isolates of
      C. gattii (n=17) were members of the VGII molecular group. With regard to mating
      types, 55 isolates were type 'alpha', and only two were type 'a'. This study
      revealed the prevalence of the VNI molecular group and provides the first
      reported observation of the VNII molecular group in the northern region of
      Brazil.

PMID- 22360143
TI  - Does working memory change with age? The interactions of concurrent articulation
      with the effects of word length and acoustic confusion.
AB  - The effects of acoustic confusion (phonological similarity), word length, and
      concurrent articulation (articulatory suppression) are cited as support for
      Working Memory's phonological loop component (e.g., Baddeley, 2000 , Psychonomic
      Bulletin and Review, 7, 544). Research has focused on younger adults, with no
      studies examining whether concurrent articulation reduces the word length and
      acoustic confusion effects among older adults. In the current study, younger and
      older adults were given lists of similar and dissimilar letters (Experiment 1) or
      long and short words (Experiment 2) for immediate serial reconstruction of order.
      Items were presented visually or auditorily, with or without concurrent
      articulation. As expected, younger and older adults demonstrated effects of
      acoustic confusion, word length, and concurrent articulation. Further, concurrent
      articulation reduced the effects of acoustic confusion and word length equally
      for younger and older adults. This suggests that age-related differences occur in
      overall performance, but do not reflect an age-related deficiency in the
      functioning of the phonological loop component of working memory.

PMID- 22360145
TI  - Keratocystic odontogenic tumors and Carnoy's solution: results and complications
      assessment.
AB  - OBJECTIVE: Keratocystic odontogenic tumors (KOTs) can be treated with Carnoy's
      solution, although this treatment modality is not free from complications. It is
      important to verify the incidence of complications after the use of Carnoy's
      solution and compare these with the literature. MATERIALS AND METHODS: This study
      verified the effects of a complementary treatment for KOTs and assessed the
      incidence of such complications as recurrence, infection, sequestrum formation,
      mandibular fracture, dehiscence, and neuropathy. RESULTS: Twenty-two KOTs treated
      with Carnoy's solution combined with peripheral ostectomy were included, and the
      follow-up period varied from 12 to 78months with a mean of 42.9months.
      Complications included recurrence (4.5%), dehiscence (22.7%), infection (4.5%),
      and paresthesia (18.2%). No difference was found among lesions associated (9.1%)
      or not (0%) with nevoid basal cell carcinoma syndrome (P>0.05). Dehiscence was
      influenced by marsupialization (P<0.05), and paresthesia was observed exclusively
      in cases of mandibular canal fenestration (P<0.01). CONCLUSIONS: Complementary
      treatment with Carnoy's solution and peripheral ostectomy appear to provide
      efficient treatment for KOTs. Complications originating from the use of the
      solution are less frequent and less serious than complications associated with
      cryotherapy. Neuropathy seems to be related to direct contact between the
      solution and the epineurium.

PMID- 22360146
TI  - Anthelmintic drug residues in beef: UPLC-MS/MS method validation, European retail
      beef survey, and associated exposure and risk assessments.
AB  - Anthelmintic drugs are widely used to control parasitic infections in cattle. The
      ProSafeBeef project addressed the need for data on the exposure of European
      consumers of beef to potentially harmful drug residues. A novel analytical method
      based on matrix solid-phase dispersive extraction and ultra-performance liquid
      chromatography-tandem mass spectrometry was validated for 37 anthelmintic drugs
      and metabolites in muscle (assay decision limits, CCalpha, = 0.15-10.2 ug kg-1).
      Seven European countries (France, Spain, Slovenia, Ireland, Italy, Belgium and
      Portugal) participated in a survey of retail beef purchased in local shops. Of
      1061 beef samples analysed, 26 (2.45%) contained detectable residues of
      anthelmintic drugs (0.2-171 ug kg-1), none above its European Union maximum
      residue limit (MRL) or action level. Residues detected included closantel,
      levamisole, doramectin, eprinomectin, moxidectin, ivermectin, albendazole and
      rafoxanide. In a risk assessment applied to mean residue concentrations across
      all samples, observed residues accounted for less than 0.1% of the MRL for each
      compound. An exposure assessment based on the consumption of meat at the 99th
      percentile of consumption of adults in 14 European countries demonstrated that
      beef accounted for less than 0.02% of the acceptable daily intake for each
      compound in each country. This study is the first of its kind to apply such a
      risk-based approach to an extensive multi-residue survey of veterinary drug
      residues in food. It has demonstrated that the risk of exposure of the European
      consumer to anthelmintic drug residues in beef is negligible, indicating that
      regulation and monitoring is having the desired effect of limiting residues to
      non-hazardous concentrations.

PMID- 22360147
TI  - Environmental estrogen-induced alterations of male aggression and dominance
      hierarchies in fish: a mechanistic analysis.
AB  - Environmental estrogens have been shown to affect aspects of fish behavior that
      could potentially impact on wild populations, but the physiological mechanisms
      underpinning these effects are unknown. Using small colonies of zebrafish (Danio
      rerio), we evaluated the impacts of estrogen exposure on the aggression of
      dominant males, the associated implications for their social status and
      reproductive success, and their signaling mechanisms. The aggression of dominant
      males exposed to 17alpha-ethinylestradiol (EE(2); 10 ng/L nominal) was reduced
      significantly, and half of these fish subsequently lost their dominance,
      behavioral changes that were reflected in their reproductive success. Plasma
      androgen and the expression of genes involved in sex steroid production/signaling
      (cyp19a1b, cyp17, hsd11b2, hsd17b3, ar) and aggression (avplrv1b, tph1b, htr1a,
      sst1, sstr1, th, slc6a3, ar) were higher in control dominant versus subordinate
      males, but suppressed by EE(2) exposure, such that the differences between the
      social ranks were not retained. The expression levels of avpl (brain), which
      promotes aggression and dominance, and ar and cyp17 (gonad) were elevated in
      nonexposed males paired with EE(2)-exposed males. Our findings illustrate that
      disruptions of behaviors affecting social hierarchy, and in turn breeding
      outcome, as a consequence of exposure to an environmental estrogen are signaled
      through complex interconnecting gonadal and neurological control mechanisms that
      generally conform with those established in mammalian models. The extensive
      molecular, genetic, physiological, and behavioral toolbox now available for the
      zebrafish makes this species an attractive model for integrated analyses of
      chemical effects spanning behavior to molecular effect mechanisms.

PMID- 22360149
TI  - Early postmenopausal bone loss and what to do about it.
AB  - The pattern of lifelong changes in bone mass in women characterized in several
      publications generally shows that peak adult bone mass is achieved at about the
      end of adolescence or later, and begins to decline as menopause approaches.
      Uncertainties remain regarding the exact age at which peak bone mass is reached
      and when it starts to decline. The data indicate that the onset of rapid bone
      loss in healthy women begins at about two years before the last menses and is
      complete at about four to five years after the last menses. The bone loss at the
      spine, total body, and femoral neck over these years is equal to about one T
      score and is largely irreversible after it occurs. This presentation examines the
      data on these questions and focuses on the perimenopausal pattern of rapid bone
      loss and the implications for identifying and managing the later-life risk of
      fracture.

PMID- 22360150
TI  - Finding a VOICE for UK clinical pharmacology.
AB  - At a James Black Conference held in Oxford on 20-22 June 2011, a group of senior
      clinical pharmacologists and their junior colleagues, other medical specialists,
      and pharmacists discussed an agenda for UK clinical pharmacology for the next 5
      years, addressing the following broad questions. How should UK clinical
      pharmacology be further developed and delivered as a discipline in universities,
      the NHS, pharmaceutical companies, and regulatory authorities? How should
      teaching and training in UK clinical pharmacology and therapeutics be delivered
      and assessed? What topics should be priorities for research in UK academic
      clinical pharmacology? How should clinical pharmacology contribute to UK drugs
      policy? How should pharmacology and clinical pharmacology be further integrated,
      to the benefit of both? Numerous recommendations emerged, under the collective
      acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and
      Emissaries. VISIBILITY: The visibility of the discipline needs to be increased.
      This could be done, for example, by increased activities in acute general
      medicine/toxicology, through activities of Medicines and Therapeutics Committees,
      participation in grand rounds, teaching and training, and monitoring therapeutic
      interventions, and by offering bolt-on training for other specialists (for
      example, short courses, MSc courses, and training programmes). OUTREACH: Methods
      of increasing outreach include roadshows in schools/medical schools, national
      special study modules, public education, press coverage, and social marketing.
      INTEGRATION: Closer collaborations with pharmacologists, clinical pharmacists,
      other prescribers, and pharmaceutical companies (e.g. through joint training
      programmes) are desirable. COVERAGE: Attention to neglected areas, such as
      general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and
      immunology. EMISSARIES: Trainees to spread the word.

PMID- 22360151
TI  - Conformational free energy modeling of druglike molecules by metadynamics in the
      WHIM space.
AB  - Protein-ligand affinities can be significantly influenced not only by the
      interaction itself but also by conformational equilibrium of both binding
      partners, free ligand and free protein. Identification of important
      conformational families of a ligand and prediction of their thermodynamics is
      important for efficient ligand design. Here we report conformational free energy
      modeling of nine small-molecule drugs in explicitly modeled water by metadynamics
      with a bias potential applied in the space of weighted holistic invariant
      molecular (WHIM) descriptors. Application of metadynamics enhances conformational
      sampling compared to unbiased molecular dynamics simulation and allows to predict
      relative free energies of key conformations. Selected free energy minima and one
      example of transition state were tested by a series of unbiased molecular
      dynamics simulation. Comparison of free energy surfaces of free and target-bound
      Imatinib provides an estimate of free energy penalty of conformational change
      induced by its binding to the target.

PMID- 22360153
TI  - Two brief measures of executive function in the prediction of driving ability
      after acquired brain injury.
AB  - The question of fitness to drive following acquired brain injury is commonly
      encountered in rehabilitation settings. Pre-driving assessments are usually
      performed prior to on-road assessments, but there is no uniformity as to the
      instruments employed. Neuropsychological tests are often employed to assess
      different functional domains. One domain that has been suggested to be critical
      to driving is executive functioning. The present study examined the utility of
      the Frontal Assessment Battery (FAB) and the Trail Making Test Part B (TMTB) in
      predicting on-road driving performance after stroke or traumatic brain injury.
      While the TMTB has previously been demonstrated to be useful in this regard, the
      FAB has never been examined for this purpose. Participants were 76 patients
      referred for driving assessment after diagnosis of stroke or traumatic brain
      injury. Results indicated that scores on the TMTB, but not the FAB, were
      significantly predictive of on-road driving performance (p < .05). A cutoff score
      of 90 seconds or greater on the TMTB correctly identified 77% of those failing on
      road evaluation. Implications and limitations are discussed.

PMID- 22360152
TI  - A randomized trial of dalteparin compared with ibuprofen for the treatment of
      superficial thrombophlebitis.
AB  - BACKGROUND: Superficial thrombophlebitis can produce pain and result in a deep
      vein thrombosis (DVT) if not treated. Conservative therapies including
      prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been
      standard care. Recently, studies have been published reporting efficacy and
      safety of low-molecular-weight heparin for the treatment of superficial
      thrombophlebitis. However, there are few comparative trials to conservative
      therapy. We studied the effectiveness and safety of treatment with dalteparin
      compared with ibuprofen in patients with confirmed superficial thrombophlebitis.
      METHODS: Consecutive patients were randomized to receive daily dalteparin vs.
      ibuprofen three times daily for up to 14 days. The primary outcome measure was
      the incidence of extension of thrombus or new symptomatic venous thromboembolism
      during the 14-day and 3-month follow-up period. The secondary outcome was a
      reduction in pain. The outcome measure of safety was the incidence of major and
      minor bleeding. RESULTS: Of 302 consecutive patients screened, 72 were enrolled.
      Four patients receiving ibuprofen compared with no patients receiving dalteparin
      had thrombus extension at 14 days (P = 0.05), however, there was no difference in
      thrombus extension at 3 months. Both treatments significantly reduced pain. There
      were no episodes of major or minor bleeding during the treatment period.
      CONCLUSIONS: Dalteparin is superior to the NSAID ibuprofen in preventing
      extension of superficial thrombophlebitis during the 14-day treatment period with
      similar relief of pain and no increase in bleeding. However, questions concerning
      the optimal treatment duration should be explored in future trials.

PMID- 22360154
TI  - Hippocampus versus entorhinal cortex decoupling by an NR2 subunit-specific block
      of NMDA receptors in a rat in vitro model of temporal lobe epilepsy.
AB  - The role of N-methyl-D-aspartate receptors (NMDARs) in the generation and
      maintenance of epileptic seizures has been widely investigated, however, little
      is known of possible separate roles played by NMDARs that contain different NR2
      subunits. A better comprehension of how distinct NMDARs subtypes participate in
      seizure generation and/or diffusion may lead to the development of more targeted
      pharmacologic strategies to treat epilepsy. Therefore, we have performed an
      electrophysiologic investigation using a multielectrode array device, on slices
      comprising entorhinal cortex (EC) and hippocampus, continuously perfused in a
      Mg(2+) -free medium, with added 4-aminopiridine (4AP; 10-15 MUm). Two separate
      rhythmic patterns of interictal-like activity were generated in EC and
      hippocampus, with EC seizures entrained to those in CA3, so that a significant
      degree of cross-correlation occurred. Perfusion with the NR2A-containing NMDAR
      antagonist [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4
      tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077; 50 nm) or Zn(2+)
      (200 nm), did not affect the rate of interictal-like events in EC and
      hippocampus; however, it significantly reduced their cross-correlation, causing a
      substantial decoupling of the two rhythm generators. The same effect was observed
      with (alphaR,betaS)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1
      piperidinepropanol maleate (Ro25-6981; 1 MUm), when coapplied with a subthreshold
      dose of NVP-AAM077. Our results suggest that NR2 subunits may be crucial in
      entraining cortical networks, leading to recruitment of wider range oscillations
      during epilepsy. Therefore, a pharmacologic strategy directed onto NR2 subunits
      may help to limit seizure diffusion and recruitment of potentially entrained
      oscillatory networks.

PMID- 22360155
TI  - Real-space observation of skyrmion lattice in helimagnet MnSi thin samples.
AB  - Observing and characterizing the spin distributions on a nanometer scale are of
      vital importance for understanding nanomagnetism and its application to
      spintronics. The magnetic structure in MnSi thin samples prepared from a bulk,
      which undergoes a transition from a helix to a skyrmion lattice, was investigated
      by in situ observation using Lorentz microscopy. Stripe domains were observed at
      zero applied field below 22.5 K. A skyrmion lattice with 6-fold symmetry in real
      space appeared when a field of 0.18 T was applied normal to the film plane. The
      lattice constant was estimated to be 18 nm, almost identical to the helical
      period. In comparison with the marginally stable skyrmion phase in a bulk sample,
      the skyrmion phase was stable over a wide range of temperatures and magnetic
      fields in the thin samples.

PMID- 22360156
TI  - Longer-acting and highly potent chimaeric inhibitors of excessive exocytosis
      created with domains from botulinum neurotoxin A and B.
AB  - Various human neurogenic hyper-excitability disorders are successfully treated
      with type A or B BoNT (botulinum neurotoxin). The BoNT/A complex is widely used
      because of its longer-lasting benefits; also, autonomic side-effects are more
      often reported for BoNT/B. To establish if this distinct effect of BoNT/B could
      be exploited therapeutically, BoNT/A was modified so that it would bind the more
      abundant BoNT/B acceptor in rodents while retaining its desirable persistent
      action. The advantageous protease and translocation domain of BoNT/A were
      recombinantly combined with the acceptor-binding moiety of type B [H(C)/B (C
      terminal half of BoNT/B heavy chain)], creating the chimaera AB. This purified
      protein bound the BoNT/B acceptor, displayed enhanced capability relative to type
      A for intraneuronally delivering its protease, cleaved SNAP-25 (synaptosome
      associated protein of 25 kDa) and induced a more prolonged neuromuscular
      paralysis than BoNT/A in mice. The BA chimaera, generated by substituting H(C)/A
      (C-terminal half of BoNT/A heavy chain) into BoNT/B, exhibited an extremely high
      specific activity, delivered the BoNT/B protease via the BoNT/A acceptor into
      neurons, or fibroblast-like synoviocytes that lack SNAP-25, cleaving the
      requisite isoforms of VAMP (vesicle-associated membrane protein). Both chimaeras
      inhibited neurotransmission in murine bladder smooth muscle. BA has the unique
      ability to reduce exocytosis from non-neuronal cells expressing the BoNT/A
      acceptor and utilising VAMP, but not SNAP-25, in exocytosis.

PMID- 22360157
TI  - Obtaining consensus about patient-centred professionalism in community nursing:
      nominal group work activity with professionals and the public.
AB  - AIM:   To report on the development of a ranked thematic list encompassing the
      positive and challenging exemplars of patient-centred professionalism in
      community nursing. BACKGROUND:   There has been little research exploring what
      'patient-centred professionalism' means to those working within the healthcare
      settings. Consensus methods, such as those developed through Nominal Group Work,
      can help establish the extent of agreement on a particular issue whilst
      overcoming some of the problems associated with group decision-making. DESIGN:  
      Mixed methods studying through consultation workshops. METHOD:   The study took
      place in South-west Wales, UK between October 2009-September 2010. Thirty-four
      participants consisting of community nurses (9), newly qualifying nurses (13),
      nursing stakeholders (6) and members of the public (6) took part in the study. An
      adapted Nominal Group Work approach was used in five individual consultation
      workshops: two with community nurses, one with newly qualifying nurses, one with
      stakeholders and one with members of the public followed by a mixed-group Forum
      event. RESULTS:   Each of the five workshops resulted in the production of
      approximately ten positive and ten challenging exemplars of patient-centred
      professionalism. The thematization of these exemplars allowed the development of
      eight broad themes. The Forum event then provided a mechanism for ranking the
      importance of these themes. The patient, community nurse as a person and nursing
      ethos were ranked as the most important themes by study participants.
      CONCLUSIONS:   The adapted Nominal Group Work approach was a useful method to
      allow the development of a ranked thematic list that illustrated the important
      positive and challenging exemplars of patient-centred professionalism in
      community nursing.

PMID- 22360158
TI  - Theoretical study of near-edge X-ray absorption fine structure spectra of metal
      phthalocyanines at C and N K-edges.
AB  - The inner shell excitation of CuPc, NiPc, and H(2)Pc phthalocyanines at both C
      and N K-edges has been investigated theoretically by density functional theory
      calculations. The selected molecules allow one to study the effect on the spectra
      of the presence and the nature of the atom in the central cavity of the
      macrocycle. The individual characteristics of the spectra can be rationalized in
      terms of the position of the unequivalent C and N atomic sites, showing that
      sensible changes are present in the spectral features deriving from the N atoms
      directly bound to the atom at the center of the Pc macrocycle. The minor
      variations present in the spectral C 1s profiles of the phthalocyanines reflect
      the little perturbation experienced by the peripheral atomic sites.

PMID- 22360159
TI  - Complications of hysteroscopic Essure((r))  sterilisation: report on 4306
      procedures performed in a single centre.
AB  - OBJECTIVE: To analyse the short-, medium- and long-term complications in women
      undergoing hysteroscopic tubal sterilisation with the Essure((r)) device. DESIGN:
      Retrospective 7-year study. SETTING: Office hysteroscopic unit in a teaching
      hospital. SAMPLE: A total of 4306 women whoe underwent the Essure((r))
      sterilisation procedure from 2003 to 2010. METHODS: Data on the success of the
      procedure and complications arising from outpatient hysteroscopic sterilisation
      using the Essure((r)) system were collected from consecutive women undergoing the
      procedure over a 7-year period. MAIN OUTCOME MEASURES: Placement rate, successful
      bilateral tubal occlusion, perioperative adverse events, early postoperative
      (during the first 3 months of follow-up) and late complications (after the
      initial 3 months of follow-up). RESULTS: A total of 4108 (96.8%) women completed
      the standard 3-month follow-up protocol. Only 534 (13%) women had undergone the
      procedure within the previous year. There were 115 (out of 4306; 2.7%) recorded
      complications, none of which resulted in the need for hospitalisation or
      discharge later than 2 hours after the procedure. Vasovagal syncope was the most
      frequently encountered adverse event, occurring in 85 (2.0%) of 4306 cases. In 19
      cases, one device was expelled, with most expulsions (14 out of 19) being
      detected before or during the 3-month follow-up. CONCLUSIONS: Outpatient
      hysteroscopic sterilisation using the Essure((r)) system is safe, with a low rate
      of complications.

PMID- 22360161
TI  - Communication: angle-resolved thermal dissociative sticking of CH4 on Pt(111):
      further indication that rotation is a spectator to the gas-surface reaction
      dynamics.
AB  - Effusive molecular beam measurements of angle-resolved thermal dissociative
      sticking coefficients for CH(4) impinging on a Pt(111) surface, at a temperature
      of 700 K, are reported and compared to theoretical predictions. The reactivity
      falls off steeply as the molecular angle of incidence increases away from the
      surface normal. Successful modeling of the thermal dissociative sticking
      behavior, consistent with existent CH(4) supersonic molecular beam experiments
      involving rotationally cold molecules, required that rotation be treated as a
      spectator degree of freedom.

PMID- 22360160
TI  - Insulin-induced microvascular recruitment in skin and muscle are related and both
      are associated with whole-body glucose uptake.
AB  - OBJECTIVE: Insulin-induced capillary recruitment is considered a determinant of
      insulin-mediated glucose uptake. Insulin action on the microvasculature has been
      assessed in skin; however, there is concern as to whether the vascular responses
      observed in skin reflect those in the muscle. We hypothesized that insulin
      induced capillary recruitment in skin would correlate with microvascular
      recruitment in muscle in a group of subjects displaying a wide variation in
      insulin sensitivity. METHODS: Capillary recruitment in skin was assessed using
      capillary videomicroscopy, and skeletal muscle microvascular recruitment (i.e.,
      increase in MBV) was studied using CEU in healthy volunteers (n = 18, mean age:
      30.6 +/- 11.1 years). Both microvascular measurements were performed during
      saline infusion, and during a hyperinsulinemic euglycemic clamp. RESULTS: During
      hyperinsulinemia, capillary recruitment in skin was augmented from 58.1 +/- 18.2%
      to 81.0 +/- 23.9% (p < 0.0001). Hyperinsulinemia increased MBV in muscle from
      7.00 (2.66-17.67) to 10.06 (2.70-41.81) units (p = 0.003). Insulin's vascular
      effect in skin and muscle was correlated (r = 0.57). Insulin's microvascular
      effects in skin and muscle showed comparable strong correlations with insulin
      mediated glucose uptake (r = 0.73 and 0.68, respectively). CONCLUSIONS: Insulin
      augmented capillary recruitment in skin parallels insulin-mediated microvascular
      recruitment in muscle and both are related to insulin-mediated glucose uptake.

PMID- 22360162
TI  - Communication: thermodynamics of condensed matter with strong pressure-energy
      correlations.
AB  - We show that for any liquid or solid with strong correlation between its NVT
      virial and potential-energy equilibrium fluctuations, the temperature is a
      product of a function of excess entropy per particle and a function of density, T
      = f(s)h(rho). This implies that (1) the system's isomorphs (curves in the phase
      diagram of invariant structure and dynamics) are described by h(rho)/T = Const.,
      (2) the density-scaling exponent is a function of density only, and (3) a
      Gruneisen-type equation of state applies for the configurational degrees of
      freedom. For strongly correlating atomic systems one has h(rho) =
      ?(n)C(n)rho(n/3) in which the only non-zero terms are those appearing in the pair
      potential expanded as nu(r) = ?(n)nu(n)r(-n). Molecular dynamics simulations of
      Lennard-Jones type systems confirm the theory.

PMID- 22360163
TI  - Accurate thermochemistry from a parameterized coupled-cluster singles and doubles
      model and a local pair natural orbital based implementation for applications to
      larger systems.
AB  - We have recently introduced a parameterized coupled-cluster singles and doubles
      model (pCCSD(alpha, beta)) that consists of a bivariate parameterization of the
      CCSD equations and is inspired by the coupled electron pair approximations. In
      our previous work, it was demonstrated that the pCCSD(-1, 1) method is an
      improvement over CCSD for the calculation of geometries, harmonic frequencies,
      and potential energy surfaces for single bond-breaking. In this paper, we find
      suitable pCCSD parameters for applications in reaction thermochemistry and
      thermochemical kinetics. The motivation is to develop an accurate and economical
      methodology that, when coupled with a robust local correlation framework based on
      localized pair natural orbitals, is suitable for large-scale thermochemical
      applications for sizeable molecular systems. It is demonstrated that the original
      pCCSD(-1, 1) method and several other pCCSD methods are a significant improvement
      upon the standard CCSD approach and that these methods often approach the
      accuracy of CCSD(T) for the calculation of reaction energies and barrier heights.
      We also show that a local version of the pCCSD methodology, implemented within
      the local pair natural orbital (LPNO) based CCSD code in ORCA, is sufficiently
      accurate for wide-scale chemical applications. The LPNO based methodology allows
      us for routine applications to intermediate sized (20-100 atoms) molecular
      systems and is a significantly more accurate alternative to MP2 and density
      functional theory for the prediction of reaction energies and barrier heights.

PMID- 22360164
TI  - Revised self-consistent continuum solvation in electronic-structure calculations.
AB  - The solvation model proposed by Fattebert and Gygi [J. Comput. Chem. 23, 662
      (2002)] and Scherlis et al. [J. Chem. Phys. 124, 074103 (2006)] is reformulated,
      overcoming some of the numerical limitations encountered and extending its range
      of applicability. We first recast the problem in terms of induced polarization
      charges that act as a direct mapping of the self-consistent continuum dielectric;
      this allows to define a functional form for the dielectric that is well behaved
      both in the high-density region of the nuclear charges and in the low-density
      region where the electronic wavefunctions decay into the solvent. Second, we
      outline an iterative procedure to solve the Poisson equation for the quantum
      fragment embedded in the solvent that does not require multigrid algorithms, is
      trivially parallel, and can be applied to any Bravais crystallographic system.
      Last, we capture some of the non-electrostatic or cavitation terms via a combined
      use of the quantum volume and quantum surface [M. Cococcioni, F. Mauri, G. Ceder,
      and N. Marzari, Phys. Rev. Lett. 94, 145501 (2005)] of the solute. The resulting
      self-consistent continuum solvation model provides a very effective and compact
      fit of computational and experimental data, whereby the static dielectric
      constant of the solvent and one parameter allow to fit the electrostatic energy
      provided by the polarizable continuum model with a mean absolute error of 0.3
      kcal/mol on a set of 240 neutral solutes. Two parameters allow to fit
      experimental solvation energies on the same set with a mean absolute error of 1.3
      kcal/mol. A detailed analysis of these results, broken down along different
      classes of chemical compounds, shows that several classes of organic compounds
      display very high accuracy, with solvation energies in error of 0.3-0.4 kcal/mol,
      whereby larger discrepancies are mostly limited to self-dissociating species and
      strong hydrogen-bond-forming compounds.

PMID- 22360165
TI  - A neural network potential-energy surface for the water dimer based on
      environment-dependent atomic energies and charges.
AB  - Understanding the unique properties of water still represents a significant
      challenge for theory and experiment. Computer simulations by molecular dynamics
      require a reliable description of the atomic interactions, and in recent decades
      countless water potentials have been reported in the literature. Still, most of
      these potentials contain significant approximations, for instance a frozen
      internal structure of the individual water monomers. Artificial neural networks
      (NNs) offer a promising way for the construction of very accurate potential
      energy surfaces taking all degrees of freedom explicitly into account. These
      potentials are based on electronic structure calculations for representative
      configurations, which are then interpolated to a continuous energy surface that
      can be evaluated many orders of magnitude faster. We present a full-dimensional
      NN potential for the water dimer as a first step towards the construction of a NN
      potential for liquid water. This many-body potential is based on environment
      dependent atomic energy contributions, and long-range electrostatic interactions
      are incorporated employing environment-dependent atomic charges. We show that the
      potential and derived properties like vibrational frequencies are in excellent
      agreement with the underlying reference density-functional theory calculations.

PMID- 22360166
TI  - Coherent control and time-dependent density functional theory: towards creation
      of wave packets by ultrashort laser pulses.
AB  - Explicitly time-dependent density functional theory (TDDFT) is a formally exact
      theory, which can treat very large systems. However, in practice it is used
      almost exclusively in the adiabatic approximation and with standard ground state
      functionals. Therefore, if combined with coherent control theory, it is not clear
      which control tasks can be achieved reliably, and how this depends on the
      functionals. In this paper, we continue earlier work in order to establish rules
      that answer these questions. Specifically, we look at the creation of wave
      packets by ultrashort laser pulses that contain several excited states. We find
      that (i) adiabatic TDDFT only works if the system is not driven too far from the
      ground state, (ii) the permanent dipole moments involved should not differ too
      much, and (iii) these results are independent of the functional used.
      Additionally, we find an artifact that produces fluence-dependent excitation
      energies.

PMID- 22360167
TI  - Transient-time correlation function applied to mixed shear and elongational
      flows.
AB  - The transient-time correlation function (TTCF) method is used to calculate the
      nonlinear response of a homogeneous atomic fluid close to equilibrium. The TTCF
      response of the pressure tensor subjected to a time-independent planar mixed flow
      of shear and elongation is compared to directly averaged non-equilibrium
      molecular dynamics (NEMD) simulations. We discuss the consequence of noise in
      simulations with a small rate of deformation. The generalized viscosity for
      planar mixed flow is also calculated with TTCF. We find that for small rates of
      deformation, TTCF is far more efficient than direct averages of NEMD simulations.
      Therefore, TTCF can be applied to fluids with deformation rates which are much
      smaller than those commonly used in NEMD simulations. Ultimately, TTCF applied to
      molecular systems is amenable to direct comparison between NEMD simulations and
      experiments and so in principle can be used to study the rheology of polymer
      melts in industrial processes.

PMID- 22360168
TI  - Critical lines for an unequal size of molecules in a binary gas-liquid mixture
      around the van Laar point using the combination of the Tompa model and the van
      der Waals equation.
AB  - We combine the modified Tompa model with the van der Waals equation to study
      critical lines for an unequal size of molecules in a binary gas-liquid mixture
      around the van Laar point. The van Laar point is coined by Meijer and it is the
      only point at which the mathematical double point curve is stable. It is the
      intersection of the tricritical point and the double critical end point. We
      calculate the critical lines as a function of chi(1) and chi(2), the density of
      type I molecules and the density of type II molecules for various values of the
      system parameters; hence the global phase diagrams are presented and discussed in
      the density-density plane. We also investigate the connectivity of critical lines
      at the van Laar point and its vicinity and discuss these connections according to
      the Scott and van Konynenburg classifications. It is also found that the critical
      lines and phase behavior are extremely sensitive to small modifications in the
      system parameters.

PMID- 22360169
TI  - Calculations of nonlinear response properties using the intermediate state
      representation and the algebraic-diagrammatic construction polarization
      propagator approach: two-photon absorption spectra.
AB  - An earlier proposed approach to molecular response functions based on the
      intermediate state representation (ISR) of polarization propagator and algebraic
      diagrammatic construction (ADC) approximations is for the first time employed for
      calculations of nonlinear response properties. The two-photon absorption (TPA)
      spectra are considered. The hierarchy of the first- and second-order ADC/ISR
      computational schemes, ADC(1), ADC(2), ADC(2)-x, and ADC(3/2), is tested in
      applications to H(2)O, HF, and C(2)H(4) (ethylene). The calculated TPA spectra
      are compared with the results of coupled cluster (CC) models and time-dependent
      density-functional theory (TDDFT) calculations, using the results of the CC3
      model as benchmarks. As a more realistic example, the TPA spectrum of C(8)H(10)
      (octatetraene) is calculated using the ADC(2)-x and ADC(2) methods. The results
      are compared with the results of TDDFT method and earlier calculations, as well
      as to the available experimental data. A prominent feature of octatetraene and
      other polyene molecules is the existence of low-lying excited states with
      increased double excitation character. We demonstrate that the two-photon
      absorption involving such states can be adequately studied using the ADC(2)-x
      scheme, explicitly accounting for interaction of doubly excited configurations.
      Observed peaks in the experimental TPA spectrum of octatetraene are assigned
      based on our calculations.

PMID- 22360171
TI  - An excited state paired interacting orbital method.
AB  - A new method for analyzing and visualizing the molecular excited states, named
      "excited state paired interacting orbital (EPIO)," is proposed. The method is
      based both on the paired interacting orbital (PIO) proposed by Fujimoto and Fukui
      [J. Chem. Phys. 60, 572 (1974)] and the natural transition orbital (NTO) by
      Martin [J. Chem. Phys. 118, 4775 (2003)]. Within the PIO method, orbital
      interactions between the two fragmented molecules are represented practically
      only by a few pairs of fragment orbitals. The NTO method is a means of finding a
      compact orbital representation for the electronic transitions in the excited
      states. With the method, electronic transitions are expressed by a few particle
      hole orbital pairs and a clear picture on the electronic transitions is obtained.
      EPIO method is designed to have both properties of the preceding two methods:
      electronic transitions in composite molecular systems can be expressed with a few
      pairs of EPIOs which are constructed with fragmented molecular orbitals (MOs).
      Excited state characters, such as charge transfer and local excitations, are
      analyzed by using EPIOs with their generation probabilities. Thus, the present
      method gives us clear information on the composition of MOs which play an
      important role in the molecular excitation processes, e.g., optical processes.

PMID- 22360170
TI  - Markov processes follow from the principle of maximum caliber.
AB  - Markov models are widely used to describe stochastic dynamics. Here, we show that
      Markov models follow directly from the dynamical principle of maximum caliber
      (Max Cal). Max Cal is a method of deriving dynamical models based on maximizing
      the path entropy subject to dynamical constraints. We give three different cases.
      First, we show that if constraints (or data) are given in the form of singlet
      statistics (average occupation probabilities), then maximizing the caliber
      predicts a time-independent process that is modeled by identical, independently
      distributed random variables. Second, we show that if constraints are given in
      the form of sequential pairwise statistics, then maximizing the caliber dictates
      that the kinetic process will be Markovian with a uniform initial distribution.
      Third, if the initial distribution is known and is not uniform we show that the
      only process that maximizes the path entropy is still the Markov process. We give
      an example of how Max Cal can be used to discriminate between different dynamical
      models given data.

PMID- 22360172
TI  - Vibronic coupling simulations for linear and nonlinear optical processes:
      simulation results.
AB  - A vibronic coupling model based on time-dependent wavepacket approach is applied
      to simulate linear optical processes, such as one-photon absorbance and resonance
      Raman scattering, and nonlinear optical processes, such as two-photon absorbance
      and resonance hyper-Raman scattering, on a series of small molecules. Simulations
      employing both the long-range corrected approach in density functional theory and
      coupled cluster are compared and also examined based on available experimental
      data. Although many of the small molecules are prone to anharmonicity in their
      potential energy surfaces, the harmonic approach performs adequately. A detailed
      discussion of the non-Condon effects is illustrated by the molecules presented in
      this work. Linear and nonlinear Raman scattering simulations allow for the
      quantification of interference between the Franck-Condon and Herzberg-Teller
      terms for different molecules.

PMID- 22360173
TI  - Vibronic coupling simulations for linear and nonlinear optical processes: theory.
AB  - A comprehensive vibronic coupling model based on the time-dependent wavepacket
      approach is derived to simulate linear optical processes, such as one-photon
      absorbance and resonance Raman scattering, and nonlinear optical processes, such
      as two-photon absorbance and resonance hyper-Raman scattering. This approach is
      particularly well suited for combination with first-principles calculations.
      Expressions for the Franck-Condon terms, and non-Condon effects via the Herzberg
      Teller coupling approach in the independent-mode displaced harmonic oscillator
      model are presented. The significance of each contribution to the different
      spectral types is discussed briefly.

PMID- 22360174
TI  - Density functional theory guided Monte Carlo simulations: application to melting
      of Na13.
AB  - We present a density functional theory (DFT) based Monte Carlo simulation method
      in which a simple energy function gets fitted on-the-fly to DFT energies and
      gradients. The fitness of the energy function gets tested periodically using the
      classical importance function technique [R. Iftimie, D. Salahub, D. Wei, and J.
      Schofield, J. Chem. Phys. 113, 4852 (2000)]. The function is updated to fit the
      DFT energies and gradients of the most recent structures visited whenever it
      fails to achieve a preset accuracy. In this way, we effectively break down the
      problem of fitting the entire potential energy surface (PES) into many easier
      problems, which are to fit small local regions of the PES. We used the scaled
      Morse potential empirical function to guide a DFT Monte Carlo simulation of
      Na(13) at various temperatures. The use of empirical function guide produced a
      computational speed-up of about 7 in our test system without affecting the
      quality of the results.

PMID- 22360175
TI  - First-order phase transitions in repulsive rigid k-mers on two-dimensional
      lattices.
AB  - In a previous paper [F. Roma, A. J. Ramirez-Pastor, and J. L. Riccardo, Phys.
      Rev. B 72, 035444 (2005)], the critical behavior of repulsive rigid rods of
      length k (k-mers) on a square lattice at half coverage has been studied by using
      Monte Carlo (MC) simulations. The obtained results indicated that (1) the phase
      transition occurring in the system is a second-order phase transition for all
      adsorbate sizes k; and (2) the universality class of the transition changes from
      2D Ising-type for monomers (k = 1) to an unknown universality class for k >= 2.
      In the present work, we revisit our previous results together with further
      numerical evidences, resulting from new extensive MC simulations based on an
      efficient exchange algorithm and using high-performance computational
      capabilities. In contrast to our previous conclusions (1) and (2), the new
      numerical calculations clearly support the occurrence of a first-order phase
      transition for k >= 2. In addition, a similar scenario was found for k-mers
      adsorbed on the triangular lattice at coverage k/(2k+1).

PMID- 22360176
TI  - Survival of interacting Brownian particles in crowded one-dimensional
      environment.
AB  - We investigate a diffusive motion of a system of interacting Brownian particles
      in quasi-one-dimensional micropores. In particular, we consider a semi-infinite
      1D geometry with a partially absorbing boundary and the hard-core inter-particle
      interaction. Due to the absorbing boundary the number of particles in the pore
      gradually decreases. We present the exact analytical solution of the problem. Our
      procedure merely requires the knowledge of the corresponding single-particle
      problem. First, we calculate the simultaneous probability density of having still
      a definite number (N - k) of surviving particles at definite coordinates.
      Focusing on an arbitrary tagged particle, we derive the exact probability density
      of its coordinate. Second, we present a complete probabilistic description of the
      emerging escape process. The survival probabilities for the individual particles
      are calculated, the first and the second moments of the exit times are discussed.
      Generally speaking, although the original inter-particle interaction possesses a
      point-like character, it induces entropic repulsive forces which, e.g., push the
      leftmost (rightmost) particle towards (opposite) the absorbing boundary thereby
      accelerating (decelerating) its escape. More importantly, as compared to the
      reference problem for the non-interacting particles, the interaction changes the
      dynamical exponents which characterize the long-time asymptotic dynamics.
      Interesting new insights emerge after we interpret our model in terms of (a)
      diffusion of a single particle in a N-dimensional space, and (b) order statistics
      defined on a system of N-independent, identically distributed random variables.

PMID- 22360177
TI  - Far-from-equilibrium processes without net thermal exchange via energy sorting.
AB  - Many important processes at the microscale require far-from-equilibrium
      conditions to occur, as in the functioning of mesoscopic bioreactors, nanoscopic
      rotors, and nanoscale mass conveyors. Achieving such conditions, however, is
      typically based on energy inputs that strongly affect the thermal properties of
      the environment and the controllability of the system itself. Here, we present a
      general class of far-from-equilibrium processes that suppress the net thermal
      exchange with the environment by maintaining the Maxwell-Boltzmann velocity
      distribution intact. This new phenomenon, referred to as ghost equilibrium,
      results from the statistical cancellation of superheated and subcooled
      nonequilibrated degrees of freedom that are autonomously generated through a
      microscale energy sorting process. We provide general conditions to observe this
      phenomenon and study its implications for manipulating energy at the microscale.
      The results are applied explicitly to two mechanistically different cases, an
      ensemble of rotational dipoles and a gas of trapped particles, which encompass a
      great variety of common situations involving both rotational and translational
      degrees of freedom.

PMID- 22360178
TI  - A generalized gradient approximation for exchange derived from the model
      potential of van Leeuwen and Baerends.
AB  - The common way to obtain energies from Kohn-Sham exchange potentials is by using
      the Levy-Perdew virial relation. For potentials that are not functional
      derivatives (i.e., nearly all model exchange potentials in existence), this
      approach leads to energy expressions that lack translational and rotational
      invariance. We propose a method for constructing potential-based energy
      functionals that are free from these artifacts. It relies on the same line
      integration technique that gives rise to the Levy-Perdew relation, but uses
      density scaling instead of coordinate scaling. The method is applicable to any
      exchange or correlation potential that depends on the density explicitly, and
      correctly recovers the parent energy functional from a functional derivative. To
      illustrate our approach we develop a properly invariant generalized gradient
      approximation for exchange starting from the model potential of van Leeuwen and
      Baerends.

PMID- 22360179
TI  - State-to-state reaction probabilities within the quantum transition state
      framework.
AB  - Rigorous quantum dynamics calculations of reaction rates and initial state
      selected reaction probabilities of polyatomic reactions can be efficiently
      performed within the quantum transition state concept employing flux correlation
      functions and wave packet propagation utilizing the multi-configurational time
      dependent Hartree approach. Here, analytical formulas and a numerical scheme
      extending this approach to the calculation of state-to-state reaction
      probabilities are presented. The formulas derived facilitate the use of three
      different dividing surfaces: two dividing surfaces located in the product and
      reactant asymptotic region facilitate full state resolution while a third
      dividing surface placed in the transition state region can be used to define an
      additional flux operator. The eigenstates of the corresponding thermal flux
      operator then correspond to vibrational states of the activated complex.
      Transforming these states to reactant and product coordinates and propagating
      them into the respective asymptotic region, the full scattering matrix can be
      obtained. To illustrate the new approach, test calculations study the D +
      H(2)(nu, j) -> HD(nu', j') + H reaction for J = 0.

PMID- 22360180
TI  - Electromagnetically induced transparency spectroscopy.
AB  - We propose a method based on the electromagnetically induced transparency (EIT)
      phenomenon for the detection of molecules which exist as a small minority in the
      presence of a majority of absorbers. The EIT effect we employ effectively
      eliminates the absorption of the majority species in the spectral region where it
      overlaps with the absorption of the minority species. The method can also be used
      to enhance local-modes transitions which overlap spectrally with a background of
      other local-modes transitions of the same molecule. The general theory is applied
      to the case of sparse and congested background spectra within the same molecule
      and to the recording of the spectra of isotopomers (of chlorine and methanol)
      that are in minority relative to other isotopomers which constitute the majority
      of molecules present.

PMID- 22360181
TI  - Gas-phase structures of neutral silicon clusters.
AB  - Vibrational spectra of neutral silicon clusters Si(n), in the size range of n = 6
      10 and for n = 15, have been measured in the gas phase by two fundamentally
      different IR spectroscopic methods. Silicon clusters composed of 8, 9, and 15
      atoms have been studied by IR multiple photon dissociation spectroscopy of a
      cluster-xenon complex, while clusters containing 6, 7, 9, and 10 atoms have been
      studied by a tunable IR-UV two-color ionization scheme. Comparison of both
      methods is possible for the Si(9) cluster. By using density functional theory, an
      identification of the experimentally observed neutral cluster structures is
      possible, and the effect of charge on the structure of neutrals and cations,
      which have been previously studied via IR multiple photon dissociation, can be
      investigated. Whereas the structures of small clusters are based on bipyramidal
      motifs, a trigonal prism as central unit is found in larger clusters. Bond
      weakening due to the loss of an electron leads to a major structural change
      between neutral and cationic Si(8).

PMID- 22360182
TI  - Absorption by DNA single strands of adenine isolated in vacuo: the role of
      multiple chromophores.
AB  - The degree of electronic coupling between DNA bases is a topic being up for much
      debate. Here we report on the intrinsic electronic properties of isolated DNA
      strands in vacuo free of solvent, which is a good starting point for high-level
      excited states calculations. Action spectra of DNA single strands of adenine
      reveal sign of exciton coupling between stacked bases from blueshifted absorption
      bands (~3 nm) relative to that of the dAMP mononucleotide (one adenine base). The
      bands are blueshifted by about 10 nm compared to those of solvated strands, which
      is a shift similar to that for the adenine molecule and the dAMP mononucleotide.
      Desolvation has little effect on the bandwidth, which implies that inhomogenous
      broadening of the absorption bands in aqueous solution is of minor importance
      compared to, e.g., conformational disorder. Finally, at high photon energies,
      internal conversion competes with electron detachment since dissociation of the
      bare photoexcited ions on the microsecond time scale is measured.

PMID- 22360183
TI  - New determination of the adiabatic ionization potential of the BaOH radical from
      laser photoionization-molecular beam experiments and ab initio calculations.
AB  - The adiabatic ionization potential of the BaOH radical, as generated in a laser
      vaporization-supersonic expansion source has been determined by laser
      photoionization experiments to be (4.55 +/- 0.03) eV. This value supports the
      three lowest out of seven previous experimental estimates, the former ranging
      from 4.35 to 4.62 eV. The present result is compared to ab initio calculations,
      as performed using both quantum chemistry at different levels of theory and
      density functional theory, and trying several effective core potentials and their
      accompanying basis sets for Ba. The most satisfactory agreement is obtained for
      either the adiabatic or vertical ionization potentials that derive from post
      Hartree-Fock [MP2 and CCSD(T)] treatments of electron correlation, along with
      consideration of relativistic effects and extensive basis sets for Ba, in both
      BaOH and BaOH(+). Such conclusions extend to the results of related calculations
      on the Ba-OH dissociation energies of BaOH and BaOH(+), which were performed to
      help in calibrating the present computational study. Bonding in BaOH/BaOH(+), as
      well as possible sources of discrepancy with previous experimental determinations
      of the BaOH adiabatic ionization potential are discussed.

PMID- 22360184
TI  - B1(1)Pi state of KCs: high-resolution spectroscopy and description of low-lying
      energy levels.
AB  - The diode laser induced B(1)(1)Pi -> X(1)Sigma(+) fluorescence spectra of the KCs
      molecule were recorded by Fourier-transform spectrometer with resolution of 0.03
      cm(-1). Buffer gas Ar was used to facilitate appearance of rotation relaxation
      lines in the spectra, thus enlarging the B(1)(1)Pi dataset, allowing one to
      determine the Lambda-splitting constants and to reveal numerous local
      perturbations. A dataset was systematically obtained for B(1)(1)Pi vibrational
      levels nu(') ? [0; 5] nonuniformly covering rotational levels with J(') ? [7;
      233]. For nu(') ? [0; 3], the less-perturbed data of f-components were included
      in the fit. A pointwise potential energy curve (PEC) based on the inverted
      perturbation approach, as well as the Dunham coefficients, was obtained and
      compared with ab initio calculations; in particular, the energy of the PEC's
      minimum T(e) = 14,044.918(6) cm(-1) was determined. Both approaches allowed us to
      reproduce the vast majority of data used in the fit with accuracy of 0.02 cm(-1).
      Tentative molecular constants for several vibrational levels of the near lying
      C(3)(1)Sigma(+) state were estimated.

PMID- 22360185
TI  - Electronic spectroscopy of jet-cooled YbNH3.
AB  - We report the first spectroscopic study of a complex consisting of a rare earth
      atom in combination with ammonia. Using two-color resonance-enhanced multiphoton
      ionization (REMPI) spectroscopy, the lowest energy electronic transition of
      YbNH(3) has been found in the near-infrared. The spectrum arises from a spin
      forbidden transition between the (1)A(1) ground electronic state and the lowest
      (3)E excited electronic state. The transition is metal centered and approximately
      correlates with the Yb 6s6p (3)P <- 6s(2) (1)S transition. The observation of
      clear spin-orbit structure in the spectrum confirms the C(3v) symmetry of
      YbNH(3). Vibrational structure is also observed in the REMPI spectrum, which is
      dominated by excitation of the Yb-N stretching vibration.

PMID- 22360186
TI  - Molecular geometry of OC...AgI determined by broadband rotational spectroscopy
      and ab initio calculations.
AB  - Pure rotational spectra of the ground vibrational states of six isotopologues of
      OC...AgI have been measured by chirped-pulse Fourier transform microwave
      spectroscopy. The spectra are assigned to determine the rotational constant,
      B(0), centrifugal distortion constant, D(J), and nuclear quadrupole coupling
      constant of the iodine atom, chi(aa)(I). The complex is linear. Isotopic
      substitutions at the silver, carbon, and oxygen atoms allow bond lengths to be
      established by the r(0), r(s), and r(m)((1)) methods of structure determination.
      The length of the C-O bond, r(CO), in the r(0) geometry for OC...AgI is 0.008 A
      shorter than that found in the free CO molecule. The length of the Ag-I bond,
      r(AgI), is 0.013 A shorter than in free AgI. chi(aa)(I) is determined to be 
      769.84(22) MHz for OC...(107)AgI implying an ionic character of 0.66 for the
      metal halide bond. Attachment of carbon monoxide to the isolated AgI molecule
      results in an increase of the ionic character of AgI of 0.12. The molecular
      structure and spectroscopic parameters determined from the experimental data are
      presented alongside the results of calculations at the explicitly correlated
      coupled-cluster singles, doubles and perturbative triples level. Vibrational
      frequencies, the electric dipole moment, the nuclear quadrupole coupling
      constant, and the dissociation energy of the molecule have been calculated.

PMID- 22360187
TI  - Photoelectron spectroscopy of 1-nitropropane and 1-nitrobutane anions.
AB  - We present low-energy velocity map photoelectron imaging results for bare and Ar
      solvated 1-nitropropane and 1-nitrobutane anions. We report the adiabatic
      electron affinity of 1-nitropropane as (223 +/- 6) meV and that of 1-nitrobutane
      as (240 +/- 6 meV). The vertical detachment energies of these two species are
      found to be (0.92 +/- 0.05) and (0.88 +/- 0.05) eV, respectively. The
      photoelectron spectra are discussed in the framework of Franck-Condon simulations
      based on density functional theory. We observe unusual resonances in the
      photoelectron spectra of both ions under study, whose kinetic energy is
      independent of the photon energy of the detaching radiation. We discuss possible
      origins of these resonances as rescattering phenomena, consistent with the
      experimental photoelectron angular distributions.

PMID- 22360188
TI  - The Jahn-Teller effect in CH3Cl+(X2E): a combined high-resolution experimental
      measurement and ab initio theoretical study.
AB  - The energy levels of CH(3)Cl(+)X(2)E showing strong spin-vibronic coupling effect
      (Jahn-Teller effect) have been measured up to 3500 cm(-1) above the ground
      vibrational state using one-photon zero-kinetic energy photoelectron and mass
      analyzed threshold ionization spectroscopic method. Theoretical calculations have
      been also performed to calculate the spin-vibronic energy levels using a diabatic
      model and ab initio adiabatic potential energy surfaces (PESs). In the
      theoretical calculations the diabatic potential energy surfaces are expanded by
      the Taylor expansions up to the fourth-order including the multimode vibronic
      interactions. The calculated spin-orbit energy splitting (224.6 cm(-1)) for the
      ground vibrational state is in good agreement with the experimental data (219 +/-
      3 cm(-1)), which indicates that the Jahn-Teller and the spin-orbit coupling have
      been properly described in the theoretical model near the zero-point energy
      level. Based on the assignments predicted by the theoretical calculations, the
      experimentally measured energy levels were fitted to those from the diabatic
      model by optimizing the main spectroscopic parameters. The PESs from the ab
      initio calculations at the level of CASPT2/vq(t)z were thus compared with those
      calculated from the experimentally determined spectroscopic parameters. The
      theoretical diagonal elements in the diabatic potential matrix are in good
      agreement with those determined using the experimental data, however, the
      theoretical off-diagonal elements appreciably deviate from those determined using
      the experimental data for geometric points far away from the conical
      intersections. It is also concluded that the JT effect in CH(3)Cl(+) mainly
      arises from the linear coupling and the mode coupling between the CH(3) deform
      (upsilon(5)) and CH(3) rock (upsilon(6)) vibrations. The mode couplings between
      the symmetric C-Cl stretching vibration upsilon(3) with upsilon(5) and upsilon(6)
      are also important to understand the spin-vibronic structure of the molecule.

PMID- 22360189
TI  - Structure and properties of metal-exchanged zeolites studied using gradient
      corrected and hybrid functionals. I. Structure and energetics.
AB  - The structural and energetic properties of purely siliceous, proton-, and Cu- and
      Co-exchanged chabazite have been studied using periodic density-functional (DFT)
      calculations with both conventional gradient-corrected exchange-correlation
      functionals and hybrid functionals mixing exact (i.e., Hartree-Fock) and DFT
      exchange. Spin-polarized and fixed-moment calculations have been performed to
      determine the equilibrium and excited spin-configurations of the metal-exchanged
      chabazites. For the purely siliceous chabazite, hybrid functionals predict a
      slightly more accurate cell volume and lattice geometry. For isolated Al/Si
      substitution sites, gradient-corrected functionals predict that the lattice
      distortion induced by the substitution preserves the local tetrahedral symmetry,
      whereas hybrid functionals lead to a distorted Al coordination with two short and
      two long Al-O bonds. Hybrid functionals yield a stronger cation-framework binding
      that conventional functionals in metal-exchanged zeolites, they favor shorter
      cation-oxygen bonds and eventually also a higher coordination of the cation. Both
      types of functionals predict the same spin in the ground-state. The structural
      optimization of the excited spin-states shows that the formation of a high-spin
      configuration leads to a strong lattice relaxation and a weaker cation-framework
      bonding. For both Cu- and Co-exchanged chabazite, the prediction of a preferred
      location of the cation in a six-membered ring of the zeolite agrees with
      experiment, but the energy differences between possible cation locations and the
      lattice distortion induced by the Al/Si substitution and the bonding of the
      cation depends quite significantly on the choice of the functional. All
      functionals predict similar energy differences for excited spin states. Spin
      excitations are shown to be accompanied by significant changes in the cation
      coordination, which are more pronounced with hybrid functionals. The consequences
      of electronic spectra and chemical reactivity are analyzed in the following
      papers.

PMID- 22360190
TI  - Structure and properties of metal-exchanged zeolites studied using gradient
      corrected and hybrid functionals. II. Electronic structure and photoluminescence
      spectra.
AB  - The influence of the choice of the exchange-correlation functional (semilocal
      gradient corrected or hybrid functionals) on the electronic properties of metal
      exchanged zeolites has been investigated for Cu- and Co-exchanged chabazite. The
      admixture of exact exchange in hybrid functionals increases the fundamental gap
      of purely siliceous chabazite, leading to better agreement with experiment and
      many-body perturbation theory for close-packed SiO(2) polymorphs where detailed
      experimental information is available. For the metal-exchanged chabazite the
      increased exchange splitting strongly influences the position of the cation
      states relative to the framework bands-in general, gradient-corrected functionals
      locate the occupied cation states close to the valence-band maximum of the
      framework, while hybrid functionals shift the occupied cation states to larger
      binding energies and the empty states to higher energies within the fundamental
      gap. The photoluminescence spectra have been analyzed using fixed-moment total
      energy calculations for excited spin states in structurally relaxed and frozen
      geometries. The geometrical relaxation of the excited states leads to large
      differences in excitation and emission energies which are more pronounced in
      calculations using hybrid functionals. Due to the stronger relaxation effects
      calculated with hybrid functionals, the large differences in the electronic
      spectra calculated with both types of functionals are not fully reflected in the
      photoluminescence spectra.

PMID- 22360191
TI  - Structure and properties of metal-exchanged zeolites studied using gradient
      corrected and hybrid functionals. III. Energetics and vibrational spectroscopy of
      adsorbates.
AB  - The influence of the exchange-correlation functional (semilocal gradient
      corrected or hybrid functional) on density-functional studies of the adsorption
      of CO and NO in Cu- and Co-exchanged chabazite has been investigated, extending
      the studies of the structural and electronic properties of these materials [F.
      Goltl and J. Hafner, J. Chem. Phys. 136, 064501 (2012); 136, 064502 (2012)] and
      including for comparison carbonyls and nitrosyls of Cu and Co. Hybrid functionals
      predict much lower adsorption energies than conventional semilocal functionals,
      in better agreement with experiment as far as data are available for comparison.
      The calculated adsorption energies show a strong linear correlation with the
      stability of the cation sites. For Cu(I)-chabazite the calculated adsorption
      energies span almost the interval between the adsorption energies calculated for
      pure neutral and positively charged Cu-carbonyls and nitrosyls. For divalent
      Cu(II) and Co(II) the adsorption energies at cations in chabazite are much lower
      than the metal-molecule binding energies in the free carbonyls or nitrosyls,
      especially for the most stable cation location in a six-membered ring of the
      chabazite structure. For the stretching modes of adsorbed CO only hybrid
      functionals reproduce the blueshift of the frequency reported for all Cu(I)- and
      Co(II)-zeolites. For Cu(II)-chabazite both types of functionals predict a
      blueshift, the larger value calculated with hybrid functionals being in better
      agreement with observation. For NO adsorbed on Cu(I)-chabazite all functionals
      produce a redshift, the smaller value derived with hybrid functionals being in
      better agreement with experiment. For NO adsorbed in Cu(II)- and Co(II)-chabazite
      gradient-corrected functionals produce the best agreement with experiment for
      cations located in a six-membered ring. Semilocal functionals tend to
      underestimate the frequencies, while hybrid functionals tend to overestimate. The
      decisive factors determining the influence of the functionals are the larger HOMO
      LUMO gap and the larger bandgap of the zeolite host, as well as the larger
      exchange-splitting of the cation eigenstates predicted with hybrid functionals.
      For Co(II)-chabazite the tendency to overestimate the exchange-splitting and to
      stabilize a high-spin state lead to better results with semilocal functionals.
      Finally, a comprehensive discussion of the influence of the exchange-correlation
      functional on the physico-chemical properties of these complex systems, based all
      three papers of this series is presented.

PMID- 22360192
TI  - Analysis of time resolved femtosecond and femtosecond/picosecond coherent anti
      Stokes Raman spectroscopy: application to toluene and Rhodamine 6G.
AB  - The third-order polarization for coherent anti-Stokes Raman scattering (CARS)
      from a pure state is described by 48 terms in perturbation theory, but only 4
      terms satisfy the rotating wave approximation. They are represented by Feynman
      dual time-line diagrams and four-wave mixing energy level diagrams. In time
      resolved (tr) fs and fs/ps CARS from the ground vibrational state, one resonant
      diagram, which is the typical CARS term, with three field interactions-pump,
      Stokes, followed by probe-on the ket is dominant. Using the separable, displaced
      harmonic oscillators approximation, an analytic result is obtained for the four
      time correlation function in the CARS third-order polarization. Dlott's
      phenomenological expression for off-resonance CARS from the ground vibrational
      state is derived using a three-state model. We calculated the tr fs and fs/ps
      CARS for toluene and Rhodamine 6G (R6G), initially in the ground vibrational
      state, to compare with experimental results. The observed vibrational features
      and major peaks for both tr fs and fs/ps CARS, from off-resonance (for toluene)
      to resonance (for R6G) pump wavelengths, can be well reproduced by the
      calculations. The connections between fs/ps CARS, fs stimulated Raman
      spectroscopy, and impulsive stimulated scattering for toluene and R6G are
      discussed.

PMID- 22360193
TI  - Selective probe of the morphology and local vibrations at carbon nanoasperities.
AB  - We introduce a way to selectively probe local vibration modes at nanostructured
      asperities such as tips of carbon nanohorns. Our observations benefit from signal
      amplification in surface-enhanced Raman scattering (SERS) at sites near a silver
      surface. We observe nanohorn tip vibration modes in the range 200-500 cm(-1),
      which are obscured in regular Raman spectra. Ab initio density functional
      calculations assign modes in this frequency range to local vibrations at the
      nanohorn cap resembling the radial breathing mode of fullerenes. Careful
      interpretation of our SERS spectra indicates presence of caps with 5 or 6
      pentagons, which are chemically the most active sites. Changes in the peak
      intensities and frequencies with time indicate that exposure to laser irradiation
      may cause structural rearrangements at the cap.

PMID- 22360194
TI  - Elucidation of spin echo small angle neutron scattering correlation functions
      through model studies.
AB  - Several single-modal Debye correlation functions to approximate part of the
      overall Debey correlation function of liquids are closely examined for
      elucidating their behavior in the corresponding spin echo small angle neutron
      scattering (SESANS) correlation functions. We find that the maximum length scale
      of a Debye correlation function is identical to that of its SESANS correlation
      function. For discrete Debye correlation functions, the peak of SESANS
      correlation function emerges at their first discrete point, whereas for
      continuous Debye correlation functions with greater width, the peak position
      shifts to a greater value. In both cases, the intensity and shape of the peak of
      the SESANS correlation function are determined by the width of the Debye
      correlation functions. Furthermore, we mimic the intramolecular and
      intermolecular Debye correlation functions of liquids composed of interacting
      particles based on a simple model to elucidate their competition in the SESANS
      correlation function. Our calculations show that the first local minimum of a
      SESANS correlation function can be negative and positive. By adjusting the
      spatial distribution of the intermolecular Debye function in the model, the
      calculated SESANS spectra exhibit the profile consistent with that of hard-sphere
      and sticky-hard-sphere liquids predicted by more sophisticated liquid state
      theory and computer simulation.

PMID- 22360195
TI  - First principles analysis of the initial oxidation of Si(001) and Si(111)
      surfaces terminated with H and CH3.
AB  - Transition state analyses have been carried out within a density functional
      theory setting to explain and quantify the distinctly different ways in which
      hydrogen and methyl terminations serve to protect silicon surfaces from the
      earliest onset of oxidation. We find that oxidation occurs via direct
      dissociative adsorption, without any energy barrier, on Si(111) and reconstructed
      Si(001) that have been hydrogen terminated; oxidation initiates with a barrier of
      only 0.05 eV on unreconstructed Si(001). The commonly measured protection
      afforded by hydrogen is shown to derive from a coverage-dependent dissociation
      rate combined with barriers to the hopping of adsorbed oxygen atoms. Methyl
      termination, in contrast, offers an additional level of protection because oxygen
      must first undergo interactions with these ligands in a three-step process with
      significant energy barriers: adsorption of O(2) into a C-H bond to form a C-O-O-H
      intermediate; decomposition of C-O-O-H into C-O-H and C=O intermediates; and,
      finally, hopping of oxygen atoms from ligands to the substrate.

PMID- 22360196
TI  - Dynamics and efficiency of a self-propelled, diffusiophoretic swimmer.
AB  - Active diffusiophoresis-swimming through interaction with a self-generated,
      neutral, solute gradient-is a paradigm for autonomous motion at the micrometer
      scale. We study this propulsion mechanism within a linear response theory. First,
      we consider several aspects relating to the dynamics of the swimming particle. We
      extend established analytical formulae to describe small swimmers, which interact
      with their environment on a finite lengthscale. Solute convection is also taken
      into account. Modeling of the chemical reaction reveals a coupling between the
      angular distribution of reactivity on the swimmer and the concentration field.
      This effect, which we term "reaction induced concentration distortion," strongly
      influences the particle speed. Building on these insights, we employ
      irreversible, linear thermodynamics to formulate an energy balance. This approach
      highlights the importance of solute convection for a consistent treatment of the
      energetics. The efficiency of swimming is calculated numerically and approximated
      analytically. Finally, we define an efficiency of transport for swimmers which
      are moving in random directions. It is shown that this efficiency scales as the
      inverse of the macroscopic distance over which transport is to occur.

PMID- 22360197
TI  - Time-resolved simultaneous polarized and depolarized light scattering system with
      high sensitivity to optical anisotropy: application to phase separation of an
      optically isotropic liquid mixture.
AB  - Depolarized light scattering is widely used to probe the spatial correlation of
      optical anisotropy in crystals, liquid crystals, and viscoelastic materials under
      stress, and a powerful means to study a non-equilibrium pattern evolution process
      of such a system. To follow the temporal change in the diagonal and off-diagonal
      contributions of the dielectric tensor, it is highly desirable to measure two
      dimensional (2D) polarized (HH: horizontally transmitted, horizontally received)
      and depolarized (VH: vertically transmitted, horizontally received) scattering
      patterns simultaneously in a time-resolved manner. We develop a light scattering
      system with a video-rate time resolution as well as very high sensitivity to
      optical anisotropy. To detect extremely weak VH scattering from a sample without
      suffering from residual birefringence of the optical system itself and leakage of
      strong HH scattering signals, we use an objective lens specially designed for
      polarizing microscopy and Glan-laser prisms, respectively. This system enables us
      to experimentally elucidate the origin of VH scattering: we use the ratio of the
      VH and HH scattering intensity as a fingerprint for whether a 2D VH scattering
      pattern is caused by (i) optical anisotropy (intrinsic birefringence) or merely
      by (ii) spatial inhomogeneity of optically isotropic materials. We verify the
      validity of this method for a process of phase separation in a binary mixture of
      isotropic liquids. The simultaneous HH and VH measurement allows us to directly
      estimate the ratio of VH and HH scattering intensity accurately. The careful
      comparison of this ratio with a simple theory unambiguously demonstrates that the
      2D VH scattering pattern is caused by the scattering angle dependence of the
      diffraction efficiency of light with the two polarization directions. That is,
      the origin of VH scattering is due to geometrical effects of the inhomogeneous
      distribution of the refractive index and not due to optical birefringence, as it
      should be for the optically isotropic sample. This method using the ratio of VH
      and HH scattering intensity may be widely used for distinguishing the two types
      of origins for a VH scattering pattern in an unambiguous manner.

PMID- 22360198
TI  - Mechanism of OH radical hydration: a comparative computational study of liquid
      and supercritical solvent.
AB  - Flexible models of the radical and water molecules including short-range
      interaction of hydrogen atoms have been employed in molecular dynamic simulation
      to understand mechanism of (?)OH hydration in aqueous systems of technological
      importance. A key role of H-bond connectivity patterns of water molecules has
      been identified. The behavior of (?)OH(aq) strongly depends on water density and
      correlates with topological changes in the hydrogen-bonded structure of water
      driven by thermodynamic conditions. Liquid and supercritical water above the
      critical density exhibit the radical localization in cavities existing in the
      solvent structure. A change of mechanism has been found at supercritical
      conditions below the critical density. Instead of cavity localization, we have
      identified accumulation of water molecules around (?)OH associated with the
      formation of a strong H-donor bond and diminution of non-homogeneity in the
      solvent structure. For all the systems investigated, the computed hydration
      number and the internal energy of hydration Delta(h)U showed approximately linear
      decrease with decreasing density of the solvent but a degree of radical-water
      hydrogen bonding exhibited non-monotonic dependence on density. The increase in
      the number of radical-water H-acceptor bonds is associated with diminution of
      extended nets of four-bonded water molecules in compressed solution at ~473 K. Up
      to 473 K, the isobaric heat of hydration in compressed liquid water remains
      constant and equal to -40 +/- 1 kJ mol(-1).

PMID- 22360199
TI  - Spontaneous tunneling and near-infrared-induced interconversion between the amino
      hydroxy conformers of cytosine.
AB  - Spontaneous and near-infrared/infrared (NIR/IR)-induced interconversions between
      two amino-hydroxy conformers of monomeric cytosine have been investigated for the
      compound isolated in a low-temperature argon matrix. Combined use of a laser
      source (which provides narrowband NIR radiation) and a broadband NIR/IR source of
      excitation light allowed a detailed investigation of mutual conversions of the
      two conformers in question. The experiments carried out within the current work
      demonstrated that upon broadband NIR/IR irradiation (with the IR source of FTIR
      spectrometer) the population ratio of the two amino-hydroxy conformers changes
      towards a ratio corresponding to a photostationary state. Evolution of the
      conformer population ratio towards the photostationary ratio occurred independent
      of the initial ratio of conformers, which could be prepared by a population shift
      (in favor of one of the forms) induced by narrowband NIR excitation. Moreover,
      spontaneous tunneling conversion of the higher-energy conformer into a lower
      energy form was observed for cytosine isolated in a low-temperature argon matrix
      kept in the dark. This process is slow and occurs on a time scale of days. The
      tunneling process, studied for matrix-isolated cytosine, clearly follows a
      dispersive type of kinetics rather than the classical monoexponential kinetics.

PMID- 22360200
TI  - Deep ultraviolet and visible crystalloluminescence of sodium chloride.
AB  - A protocol has been developed for production of intense crystalloluminescence
      (XTL) from sodium chloride in aqueous solution by selective doping with
      transition metal salts (Ag(+), Cu(2+), and Dy(3+)). The method was used to record
      complete, fully dispersed deep UV-visible (200-650 nm) XTL spectra of sodium
      chloride for the first time. The results show conclusively that the emissions are
      due to dopant cations in the NaCl lattice, with no evidence for emission directly
      from NaCl, e.g., by triboluminescence resulting from crystalline fracture. The UV
      components of the XTL spectrum are attributed to single cation substituents
      (Ag(+) and Cu(+)), and a strong visible component (~415 nm) of the XTL is
      attributed to emission from silver-pair centers, (Ag(+))(2). The nature of the
      electronic transitions of the dopant cations is discussed. The results suggest
      that the timescale for transformation of a cluster to the crystalline phase is
      rapid, with efficient relaxation to the lowest excited electronic states of the
      dopant cation. This transformation is followed by photoemission of the cation in
      the nascent crystal.

PMID- 22360201
TI  - Dynamics near a liquid-liquid phase transition in a non-tetrahedral liquid: the
      case of gallium.
AB  - We use molecular simulation to analyze liquid dynamics in the vicinity of the
      liquid-liquid phase transition (LLPT) recently discovered in the modified
      embedded-atom model for elemental gallium. For this purpose we analyze the
      diffusive behavior in terms of the mean-squared displacement and self
      intermediate scattering functions for two systems obtained by cooling the stable
      liquid through the LLPT at different cooling rates. The results show a pronounced
      heterogeneity of the dynamics upon the onset of the LLPT. Furthermore, it is
      found that this heterogeneity is closely correlated to the structural properties
      of the 9-fold coordinated high-density and 8-fold coordinated low-density liquid
      forms involved in the transition, showing a mixture of domains with very
      different diffusion time scales. The dynamics of the low-density liquid is found
      to be much more sluggish than that of the high-density form. Analysis of the
      energetics suggests that the origin of this difference is rooted in the fact that
      the cohesion in the former is significantly stronger than that in the latter.

PMID- 22360202
TI  - Commensurate-incommensurate transition of 4He adsorbed on a single C60 molecule.
AB  - Path-integral Monte Carlo calculations have been performed to study (4)He
      adsorption on a single C(60) molecule. Helium corrugations on the fullerene
      molecular surface are incorporated with the (4)He-C(60) interaction described by
      the sum of all (4)He-C interatomic pair potentials. Radial density distributions
      show a layer-by-layer growth of (4)He with the first adlayer being located at a
      distance of ~6.3 A from the center of the C(60) molecule. The monolayer shows
      different quantum states as the number of (4)He adatoms N varies. For N = 32, we
      find a commensurate solid, with each of the 32 adsorption sites on the molecular
      surface being occupied by a single (4)He atom. Various domain-wall structures are
      observed as more (4)He atoms are added and the first layer crystallizes into an
      incommensurate solid when it is completely filled. This commensurate
      incommensurate transition of the helium monolayer is found to be accompanied by
      re-entrant superfluid response at a low temperature of 0.31 K with the
      superfluidity being totally quenched at N = 32, 44, and 48. Finally, the
      different quantum states observed in the helium monolayer around C(60) are
      compared with phase diagrams proposed for the corresponding layer on a graphite
      surface.

PMID- 22360203
TI  - Emerging dynamics in surfactant-based liquid mixtures: octanoic acid/bis(2
      ethylhexyl) amine systems.
AB  - This work focuses on the dynamic phenomena emerging in self-assembled transient
      intermolecular networks formed when two different surfactants are mixed. In
      particular, the relaxation processes in liquid mixtures composed by bis(2
      ethylhexyl)amine (BEEA) and octanoic acid (OA) in the whole composition range has
      been investigated by dielectric spectroscopy and Brillouin spectroscopy. A
      thorough analysis of all the experimental data consistently suggests that, mainly
      driven by acid-base interactions arising when the two surfactants are mixed,
      supra-molecular aggregates formation causes the slowing down of molecular
      dynamics. This, in turn, reflects to longer-range relaxations. These changes have
      been found to be composition-dependent, involving strong departures of the
      mixture physico-chemical properties from an ideal behaviour, and reflecting the
      structural and dynamical features of local structures. In particular, the
      peculiar dynamic processes occurring in these local inter-molecular structures,
      have been found to be the factors responsible for the observed and quite
      surprising increase of direct-current conductivity which occurs when two
      different (and pretty non-conductive) surfactants are mixed. The discovery can be
      used not only to design novel materials for application purposes but also to shed
      more light on the basic principles regulating charge migration in structured
      liquid systems.

PMID- 22360204
TI  - Density functional theory study of CO2 capture with transition metal oxides and
      hydroxides.
AB  - We have used density functional theory (DFT) employing several different exchange
      correlation functionals (PW91, PBE, PBEsol, TPSS, and revTPSS) coupled with
      lattice dynamics calculations to compute the thermodynamics of CO(2)
      absorption/desorption reactions for selected transition metal oxides, (TMO), and
      hydroxides, TM(OH)(2), where TM = Mn, Ni, Zn, and Cd. The van't Hoff plots, which
      describe the reaction equilibrium as a function of the partial pressures of CO(2)
      and H(2)O as well as temperature, were computed from DFT total energies,
      complemented by the free energy contribution of solids and gases from lattice
      dynamics and statistical mechanics, respectively. We find that the PBEsol
      functional calculations are generally in better agreement with experimental phase
      equilibrium data compared with the other functionals we tested. In contrast, the
      formation enthalpies of the compounds are better computed with the TPSS and
      revTPSS functionals. The PBEsol functional gives better equilibrium properties
      due to a partial cancellation of errors in the enthalpies of formation. We have
      identified all CO(2) capture reactions that lie on the Gibbs free energy convex
      hull as a function of temperature and the partial pressures of CO(2) and H(2)O
      for all TMO and TM(OH)(2) systems studied here.

PMID- 22360205
TI  - How Peclet number affects microstructure and transient cluster aggregation in
      sedimenting colloidal suspensions.
AB  - We study how varying the Peclet number (Pe) affects the steady state
      sedimentation of colloidal particles that interact through short-ranged
      attractions. By employing a hybrid molecular dynamics simulation method we
      demonstrate that the average sedimentation velocity changes from a non-monotonic
      dependence on packing fraction phi at low Pe numbers, to a monotonic decrease
      with phi at higher Pe numbers. At low Pe number the pair correlation functions
      are close to their equilibrium values, but as the Pe number increases, important
      deviations from equilibrium forms are observed. Although the attractive forces we
      employ are not strong enough to form permanent clusters, they do induce transient
      clusters whose behaviour is also affected by Pe number. In particular, clusters
      are more likely to fragment and less likely to aggregate at larger Pe numbers,
      and the probability of finding larger clusters decreases with increasing Pe
      number. Interestingly, the lifetime of the clusters is more or less independent
      of Pe number in the range we study. Instead, the change in cluster distribution
      occurs because larger clusters are less likely to form with increasing Pe number.
      These results illustrate some of the subtleties that occur in the crossover from
      equilibrium like to purely non-equilibrium behaviour as the balance between
      convective and thermal forces changes.

PMID- 22360206
TI  - Correlations in liquid water for the TIP3P-Ewald, TIP4P-2005, TIP5P-Ewald, and
      SWM4-NDP models.
AB  - Water is one of the simplest molecules in existence, but also one of the most
      important in biological and engineered systems. However, understanding the
      structure and dynamics of liquid water remains a major scientific challenge.
      Molecular dynamics simulations of liquid water were performed using the water
      models TIP3P-Ewald, TIP4P-2005, TIP5P-Ewald, and SWM4-NDP to calculate the radial
      distribution functions (RDFs), the relative angular distributions, and the excess
      enthalpies, entropies, and free energies. In addition, lower-order approximations
      to the entropy were considered, identifying the fourth-order approximation as an
      excellent estimate of the full entropy. The second-order and third-order
      approximations are ~20% larger and smaller than the true entropy, respectively.
      All four models perform very well in predicting the radial distribution
      functions, with the TIP5P-Ewald model providing the best match to the
      experimental data. The models also perform well in predicting the excess entropy,
      enthalpy, and free energy of liquid water. The TIP4P-2005 and SWM4-NDP models are
      more accurate than the TIP3P-Ewald and TIP5P-Ewald models in this respect.
      However, the relative angular distribution functions of the four water models
      reveal notable differences. The TIP5P-Ewald model demonstrates an increased
      preference for water molecules to act both as tetrahedral hydrogen bond donors
      and acceptors, whereas the SWM4-NDP model demonstrates an increased preference
      for water molecules to act as planar hydrogen bond acceptors. These differences
      are not uncovered by analysis of the RDFs or the commonly employed tetrahedral
      order parameter. However, they are expected to be very important when considering
      water molecules around solutes and are thus a key consideration in modelling
      solvent entropy.

PMID- 22360207
TI  - A model electronic Hamiltonian to study low-lying electronic states of
      [Fe(bpy)3]2+ in aqueous solution.
AB  - A simple model electronic Hamiltonian to describe the potential energy surfaces
      of several low-lying d-d states of the [Fe(bpy)(3)](2+) complex is developed for
      use in molecular dynamics (MD) simulation studies. On the basis of a method
      proposed previously for first-row transition metal ions in aqueous solution, the
      model Hamiltonian is constructed using density functional theory calculations for
      the lowest singlet and quintet states. MD simulations are then carried out for
      the two spin states in aqueous solution in order to examine the performance of
      the model Hamiltonian. The simulation results indicate that the present model
      electronic Hamiltonian reasonably describes the potential energy surfaces of the
      two spin states of the aqueous [Fe(bpy)(3)](2+) system, while retaining
      sufficient simplicity for application in simulation studies on excited state
      dynamics.

PMID- 22360208
TI  - Aqueous solutions of divalent chlorides: ions hydration shell and water
      structure.
AB  - By combining neutron diffraction and Monte Carlo simulations, we have determined
      the microscopic structure of the hydration ions shell in aqueous solutions of
      MgCl(2) and CaCl(2), along with the radial distribution functions of the solvent.
      In particular the hydration shell of the cations, show cation specific symmetry,
      due to the strong and directional interaction of ions and water oxygens. The ions
      and their hydration shells likely form molecular moieties and bring clear
      signatures in the water-water radial distribution functions. Apart from these
      signatures, the influence of divalent salts on the microscopic structure of water
      is similar to that of previously investigated monovalent solutes, and it is
      visible as a shift of the second peak of the oxygen-oxygen radial distribution
      function, caused by distortion of the hydrogen bond network of water.

PMID- 22360209
TI  - The role of surface defects in multi-exciton generation of lead selenide and
      silicon semiconductor quantum dots.
AB  - Multi-exciton generation (MEG), the creation of more than one electron-hole pair
      per photon absorbed, occurs for excitation energies greater than twice the
      bandgap (E(g)). Imperfections on the surface of quantum dots, in the form of
      atomic vacancies or incomplete surface passivation, lead to less than ideal
      efficiencies for MEG in semiconductor quantum dots. The energetic onset for MEG
      is computed with and without surface defects for nanocrystals, Pb(4)Se(4), Si(7),
      and Si(7)H(2). Modeling the correlated motion of two electrons across the bandgap
      requires a theoretical approach that incorporates many-body effects, such as post
      Hartree-Fock quantum chemical methods. We use symmetry-adapted cluster with
      configuration interaction to study the excited states of nanocrystals and to
      determine the energetic threshold of MEG. Under laboratory conditions, lead
      selenide nanocrystals produce multi-excitons at excitation energies of 3 E(g),
      which is attributed to the large dielectric constant, small Coulomb interaction,
      and surface defects. In the absence of surface defects the MEG threshold is
      computed to be 2.6 E(g). For lead selenide nanocrystals with non-bonding selenium
      valence electrons, Pb(3)Se(4), the MEG threshold increases to 2.9 E(g).
      Experimental evidence of MEG in passivated silicon quantum dots places the onset
      of MEG at 2.4 E(g). Our calculations show that the lowest multi-exciton state has
      an excitation energy of 2.5 E(g), and surface passivation enhances the optical
      activity of MEG. However, incomplete surface passivation resulting in a neutral
      radical on the surface drives the MEG threshold to 4.4 E(g). Investigating the
      mechanism of MEG at the atomistic level provides explanations for experimental
      discrepancies and suggests ideal materials for photovoltaic conversion.

PMID- 22360210
TI  - Mesoscopic analysis of Gibbs' criterion for sessile nanodroplets on trapezoidal
      substrates.
AB  - By taking into account precursor films accompanying nanodroplets on trapezoidal
      substrates we show that on a mesoscopic level of description one does not observe
      the phenomenon of liquid-gas-substrate contact line pinning at substrate edges.
      This phenomenon is present in a macroscopic description and leads to non-unique
      contact angles which can take values within a range determined by the so-called
      Gibbs' criterion. Upon increasing the volume of the nanodroplet the apparent
      contact angle evaluated within the mesoscopic approach changes continuously
      between two limiting values fulfilling Gibbs' criterion, while the contact line
      moves smoothly across the edge of the trapezoidal substrate. The spatial extent
      of the range of positions of the contact line, corresponding to the variations of
      the contact angle between the values given by Gibbs' criterion, is of the order
      of ten fluid particle diameters.

PMID- 22360212
TI  - Electronic states and the influence of oxygen addition on the optical absorption
      behaviour of manganese phthalocyanine.
AB  - The effects of electronic states and air exposure on the spectroscopic properties
      of manganese phthalocyanine (MnPc) have been examined. The observed features of
      the Q-band in the absorption spectra can be explained by intrinsic electronic
      properties of MnPc, i.e., the formation of singly charged molecules by charge
      transfer excitations. However, the reaction of MnPc with atmospheric molecular
      oxygen leads to deviations in peak intensities but does not change the
      fundamental characteristics of the spectra. Nevertheless, the reaction with
      oxygen changes the spin state from S = 3/2 to S = 1/2. X-ray diffraction
      measurements also indicate a slow diffusion process of the oxygen into the MnPc
      crystal. We discuss both influences to explain the behaviour of MnPc in various
      spectroscopic methods (EELS, ellipsometry, PES). Furthermore, we support the
      experimental investigations by detailed ab-initio calculations of spectroscopic
      properties using methods of the density functional theory framework.

PMID- 22360211
TI  - Activation of water on the TiO2 (110) surface: the case of Ti adatoms.
AB  - Using first-principles calculations we have studied the reactions of water over
      Ti adatoms on the (110) surface of rutile TiO(2). Our results provide fundamental
      insights into the microscopic mechanisms that drive this reaction at the atomic
      level and assess the possibility of using this system to activate the water
      dissociation reaction. In particular, we show that a single water molecule
      dissociates exothermically with a small energy barrier of 0.17 eV. After
      dissociation, both H(+) and OH(-) ions bind strongly to the Ti adatom, which
      serves as an effective reactive center on the TiO(2) surface. Finally, clustering
      of Ti adatoms does not improve the redox activity of the system and results in a
      slightly higher energy barrier for water dissociation.

PMID- 22360213
TI  - Local structural models of complex oxygen- and hydroxyl-rich GaP/InP(001)
      surfaces.
AB  - We perform density-functional theory calculations on model surfaces to
      investigate the interplay between the morphology, electronic structure, and
      chemistry of oxygen- and hydroxyl-rich surfaces of InP(001) and GaP(001). Four
      dominant local oxygen topologies are identified based on the coordination
      environment: M-O-M and M-O-P bridges for the oxygen-decorated surface; and M-[OH]
      M bridges and atop M-OH structures for the hydroxyl-decorated surface (M = In,
      Ga). Unique signatures in the electronic structure are linked to each of the bond
      topologies, defining a map to structural models that can be used to aid the
      interpretation of experimental probes of native oxide morphology. The M-O-M
      bridge can create a trap for hole carriers upon imposition of strain or chemical
      modification of the bonding environment of the M atoms, which may contribute to
      the observed photocorrosion of GaP/InP-based electrodes in photoelectrochemical
      cells. Our results suggest that a simplified model incorporating the dominant
      local bond topologies within an oxygen adlayer should reproduce the essential
      chemistry of complex oxygen-rich InP(001) or GaP(001) surfaces, representing a
      significant advantage from a modeling standpoint.

PMID- 22360214
TI  - Graphene nanodots with intrinsically magnetic protrusions.
AB  - The three step auf bau of a triangular polyaromatic protrusion attached to a
      larger parent hexagonal shaped graphene nanodot (GND) is described and the
      dichotomy between intrinsic protrusion localized magnetism and parent extended
      zigzag edge magnetism is explored using ab initio density functional theory
      calculations of spin and charge distributions and geometry. Comparison of a three
      ring with a ten-ring protrusion-GND establishes a pattern for the magnetization
      of GNDs with larger protrusions and different morphology. The magnetism of the
      isolated protrusions arises from the mismatch in numbers of sublattice (alternant
      hydrocarbon) carbon atoms. In the parent, the sublattices are equivalent
      providing a singlet ground state and the magnetization appears only on long
      zigzag edges due to exchange interactions operating in a regime of reduced
      coulombic interactions. We demonstrate that a small protrusion can quench the
      magnetism of the edge to which it is attached. Concomitantly, the adjacent edges
      exhibit a small magnetic enhancement, while the remote edges are unperturbed.
      With size the protrusion can dominate its edge and exert control over the
      magnetization of other edges. Different multiplicities of the parent moiety were
      not found. These calculations provide guidance in understanding how the magnetism
      changes with system shape and in designing nanodots with a specific
      magnetization.

PMID- 22360215
TI  - Iron-phthalocyanine molecular junction with high spin filter efficiency and
      negative differential resistance.
AB  - We investigate the spin transport properties of iron-phthalocyanine (FePc)
      molecule sandwiched between two N-doped graphene nanoribbons (GNRs) based on the
      density functional theory and nonequilibrium Green's function methods. Our
      calculated results clearly reveal that the FePc molecular junction has high spin
      filter efficiency as well as negative differential resistance (NDR). The zero
      bias conductance through FePc molecule is dominated by the spin-down electrons,
      and the observed NDR originates from the bias-dependent effective coupling
      between the FePc molecular orbitals and the narrow density of states of
      electrodes. The remarkable high spin-filter efficiency and NDR are robust
      regardless of the edge shape and the width of GNRs, and the N-doping site in
      GNRs. These predictions indicate that FePc junction holds great promise in
      molecular electronics and spintronics applications.

PMID- 22360216
TI  - Functionality in single-molecule devices: model calculations and applications of
      the inelastic electron tunneling signal in molecular junctions.
AB  - We analyze how functionality could be obtained within single-molecule devices by
      using a combination of non-equilibrium Green's functions and ab initio
      calculations to study the inelastic transport properties of single-molecule
      junctions. First, we apply a full non-equilibrium Green's function technique to a
      model system with electron-vibration coupling. We show that the features in the
      inelastic electron tunneling spectra (IETS) of the molecular junctions are
      virtually independent of the nature of the molecule-lead contacts. Since the
      contacts are not easily reproducible from one device to another, this is a very
      useful property. The IETS signal is much more robust versus modifications at the
      contacts and hence can be used to build functional nanodevices. Second, we
      consider a realistic model of a organic conjugated molecule. We use ab initio
      calculations to study how the vibronic properties of the molecule can be
      controlled by an external electric field which acts as a gate voltage. The
      control, through the gate voltage, of the vibron frequencies and (more
      importantly) of the electron-vibron coupling enables the construction of
      functionality: nonlinear amplification and/or switching is obtained from the IETS
      signal within a single-molecule device.

PMID- 22360217
TI  - Numerical approaches to determine the interface tension of curved interfaces from
      free energy calculations.
AB  - A recently proposed method to obtain the surface free energy sigma(R) of
      spherical droplets and bubbles of fluids, using a thermodynamic analysis of two
      phase coexistence in finite boxes at fixed total density, is reconsidered and
      extended. Building on a comprehensive review of the basic thermodynamic theory,
      it is shown that from this analysis one can extract both the equimolar radius
      R(e) as well as the radius R(s) of the surface of tension. Hence the free energy
      barrier that needs to be overcome in nucleation events where critical droplets
      and bubbles are formed can be reliably estimated for the range of radii that is
      of physical interest. It is found that the conventional theory of nucleation,
      where the interface tension of planar liquid-vapor interfaces is used to predict
      nucleation barriers, leads to a significant overestimation, and this failure is
      particularly large for bubbles. Furthermore, different routes to estimate the
      effective radius-dependent Tolman length delta(R(s)) from simulations in the
      canonical ensemble are discussed. Thus we obtain an instructive exemplification
      of the basic quantities and relations of the thermodynamic theory of metastable
      droplets/bubbles using simulations. However, the simulation results for
      delta(R(s)) employing a truncated Lennard-Jones system suffer to some extent from
      unexplained finite size effects, while no such finite size effects are found in
      corresponding density functional calculations. The numerical results are
      compatible with the expectation that delta(R(s) -> infinity) is slightly negative
      and of the order of one tenth of a Lennard-Jones diameter, but much larger
      systems need to be simulated to allow more precise estimates of delta(R(s) ->
      infinity).

PMID- 22360218
TI  - How to impose stick boundary conditions in coarse-grained hydrodynamics of
      Brownian colloids and semi-flexible fiber rheology.
AB  - Long-range hydrodynamics between colloidal particles or fibers is modelled by the
      fluid particle model. Two methods are considered to impose the fluid boundary
      conditions at colloidal surfaces. In the first method radial and transverse
      friction forces between particle and solvent are applied such that the correct
      friction and torque follows for moving or rotating particles. The force
      coefficients are calculated analytically and checked by numerical simulation. In
      the second method a collision rule is used between colloidal particle and solvent
      particle that imposes the stick boundary conditions exactly. The collision rule
      comprises a generalisation of the Lowe-Anderson thermostat to radial and
      transverse velocity differences.

PMID- 22360219
TI  - Lattice cluster theory of associating polymers. I. Solutions of linear telechelic
      polymer chains.
AB  - The lattice cluster theory (LCT) for the thermodynamics of a wide array of
      polymer systems has been developed by using an analogy to Mayer's virial
      expansions for non-ideal gases. However, the high-temperature expansion inherent
      to the LCT has heretofore precluded its application to systems exhibiting strong,
      specific "sticky" interactions. The present paper describes a reformulation of
      the LCT necessary to treat systems with both weak and strong, "sticky"
      interactions. This initial study concerns solutions of linear telechelic chains
      (with stickers at the chain ends) as the self-assembling system. The main idea
      behind this extension of the LCT lies in the extraction of terms associated with
      the strong interactions from the cluster expansion. The generalized LCT for
      sticky systems reduces to the quasi-chemical theory of hydrogen bonding of
      Panyioutou and Sanchez when correlation corrections are neglected in the LCT. A
      diagrammatic representation is employed to facilitate the evaluation of the
      corrections to the zeroth-order approximation from short range correlations.

PMID- 22360220
TI  - Lattice cluster theory of associating polymers. II. Enthalpy and entropy of self
      assembly and Flory-Huggins interaction parameter chi for solutions of telechelic
      molecules.
AB  - The lattice cluster theory for solutions of telechelic polymer chains, developed
      in paper I, is applied to determine the enthalpy Deltah(p) and entropy Deltas(p)
      of self-assembly of linear telechelics and to evaluate the Flory-Huggins (FH)
      interaction parameter chi governing the phase behavior of these systems.
      Particular focus is placed on examining how these interaction variables depend on
      the composition of the solution, temperature, van der Waals and local "sticky"
      interaction energies, and the length of the individual telechelic chains. The FH
      interaction parameter chi is found to exhibit an entropy-enthalpy compensation
      effect between the "entropic" and "enthalpic" portions as either the composition
      or mass of the telechelic species is varied, providing unique theoretical
      insights into this commonly reported, yet, enigmatic phenomenon.

PMID- 22360221
TI  - The role of structure in the nonlinear mechanics of cross-linked semiflexible
      polymer networks.
AB  - The microstructural basis of the characteristic nonlinear mechanics of biopolymer
      networks remains unclear. We present a 3D network model of realistic, cross
      linked semiflexible fibers to study strain-stiffening and the effect of fiber
      volume-occupancy. We identify two structural parameters, namely, network
      connectivity and fiber entanglements, that fully govern the nonlinear response
      from small to large strains. The results also reveal distinct deformation
      mechanisms at different length scales and, in particular, the contributions of
      heterogeneity at short length scales.

PMID- 22360222
TI  - Folding of small origamis.
AB  - A model that preserves the known thermodynamic properties of double stranded DNA
      is introduced to study the formation of more complex DNA constructions, such as
      small origamis or Holliday junctions. We show that the thermodynamic behaviour of
      these complex DNA constructions is not only given by their sequence but also by
      their topology.

PMID- 22360223
TI  - Kinetic pathways to peptide aggregation on surfaces: the effects of beta-sheet
      propensity and surface attraction.
AB  - Mechanisms of peptide aggregation on hydrophobic surfaces are explored using
      molecular dynamics simulations with a coarse-grained peptide representation.
      Systems of peptides are studied with varying degrees of backbone rigidity (a
      measure of beta-sheet propensity) and degrees of attraction between their
      hydrophobic residues and the surface. Multiple pathways for aggregation are
      observed, depending on the surface attraction and peptide beta-sheet propensity.
      For the case of a single-layered beta-sheet fibril forming on the surface (a
      dominant structure seen in all simulations), three mechanisms are observed: (a) a
      condensation-ordering transition where a bulk-formed amorphous aggregate binds to
      the surface and subsequently rearranges to form a fibril; (b) the initial
      formation of a single-layered fibril in the bulk depositing flat on the surface;
      and (c) peptides binding individually to the surface and nucleating fibril
      formation by individual peptide deposition. Peptides with a stiffer chiral
      backbone prefer mechanism (b) over (a), and stronger surface attractions prefer
      mechanism (c) over (a) and (b). Our model is compared to various similar
      experimental systems, and an agreement was found in terms of the surface
      increasing the degree of fibrillar aggregation, with the directions of fibrillar
      growth matching the crystallographic symmetry of the surface. Our simulations
      provide details of aggregate growth mechanisms on scales inaccessible to either
      experiment or atomistic simulations.

PMID- 22360224
TI  - Non-Hermitian exciton dynamics in a photosynthetic unit system.
AB  - The non-Hermitian quantum dynamics of excitonic energy transfer in photosynthetic
      systems is investigated using a dissipative two-level dimer model. The approach
      is based on Green's function formalism which permits consideration of decoherence
      and intersite transfer processes on comparable terms. The results indicate a
      combination of coherent and incoherent behavior at higher temperatures with the
      possibility of exceptional points occurring at the coherent-incoherent crossover
      regime at critical temperatures. When each dimer site is coupled equally to the
      environmental sources of dissipation, the excitonic wavepacket evolves with time
      with a coherent component, which can be attributed to the indistinguishability of
      the sources of dissipation. The time evolution characteristics of the B850 Bchls
      dimer system is analysed using typical parameter estimates in photosynthetic
      systems, and the quantum brachistochrone passage times are obtained for a range
      of parameters.

PMID- 22360225
TI  - Polymer translocation in solid-state nanopores: dependence of scaling behavior on
      pore dimensions and applied voltage.
AB  - We investigate unforced and forced translocation of a Rouse polymer (in the
      absence of hydrodynamic interactions) through a silicon nitride nanopore by three
      dimensional Langevin dynamics simulations, as a function of pore dimensions and
      applied voltage. Our nanopore model consists of an atomistically detailed
      nanopore constructed using the crystal structure of beta-Si(3)N(4). We also use
      realistic parameters in our simulation models rather than traditional
      dimensionless quantities. When the polymer length is much larger than the pore
      length, we find the translocation time versus chain length scales as tau ~
      N(2+nu) for the unforced case and as tau ~ N((1+2nu)/(1+nu)) for the forced case.
      Our results agree with theoretical predictions which indicate that memory effects
      and tension on the polymer chain play an important role during the translocation
      process. We also find that the scaling exponents are highly dependent on the
      applied voltage (force). When the length of the polymer is on the order of the
      length of the pore, we do not find a continuous scaling law, but rather scaling
      exponents that increase as the length of the polymer increases. Finally, we
      investigate the scaling behavior of translocation time versus applied voltage for
      different polymer and pore lengths. For long pores, we obtain the theoretical
      scaling law of tau ~ 1/V(alpha), where alpha ? 1 for all voltages and polymer
      lengths. For short pores, we find that alpha decreases for very large voltages
      and/or small polymer lengths, indicating that the value of alpha = 1 is not
      universal. The results of our simulations are discussed in the context of
      experimental measurements made under different conditions and with differing pore
      geometries.

PMID- 22360226
TI  - Unzipping and binding of small interfering RNA with single walled carbon
      nanotube: a platform for small interfering RNA delivery.
AB  - In an effort to design efficient platform for siRNA delivery, we combine all atom
      classical and quantum simulations to study the binding of small interfering RNA
      (siRNA) by pristine single wall carbon nanotube (SWCNT). Our results show that
      siRNA strongly binds to SWCNT surface via unzipping its base-pairs and the
      propensity of unzipping increases with the increase in the diameter of the
      SWCNTs. The unzipping and subsequent wrapping events are initiated and driven by
      van der Waals interactions between the aromatic rings of siRNA nucleobases and
      the SWCNT surface. However, molecular dynamics (MD) simulations of double strand
      DNA (dsDNA) of the same sequence show that the dsDNA undergoes much less
      unzipping and wrapping on the SWCNT in the simulation time scale of 70 ns. This
      interesting difference is due to smaller interaction energy of thymidine of dsDNA
      with the SWCNT compared to that of uridine of siRNA, as calculated by dispersion
      corrected density functional theory (DFT) methods. After the optimal binding of
      siRNA to SWCNT, the complex is very stable which serves as one of the major
      mechanisms of siRNA delivery for biomedical applications. Since siRNA has to
      undergo unwinding process with the effect of RNA-induced silencing complex, our
      proposed delivery mechanism by SWCNT possesses potential advantages in achieving
      RNA interference.

PMID- 22360228
TI  - Communication: variational many-body expansion: accounting for exchange
      repulsion, charge delocalization, and dispersion in the fragment-based explicit
      polarization method.
AB  - A fragment-based variational many-body (VMB) expansion method is described to
      directly account for exchange repulsion, charge delocalization (charge transfer)
      and dispersion interactions in the explicit polarization (X-Pol) method. The
      present VMB/X-Pol approach differs from other fragment molecular orbital (FMO)
      techniques in two major aspects. First, the wave function for the monomeric
      system is variationally optimized using standard X-Pol method, as opposed to the
      iterative update procedure adopted in FMO. Second, the mutual polarizations in
      the dimeric terms are also variationally determined, whereas single-point energy
      calculations of the individual dimers embedded in a static monomer field are used
      in FMO. The second-order (two-body) VMB (VMB2) expansion method is illustrated on
      a series of water hexamer complexes and one decamer cluster, making use of
      Hartree-Fock theory, MP2, and the PBE1 and M06 density functionals to represent
      the monomer and dimer fragments. The computed binding energies are within 2
      kcal/mol of the corresponding results from fully delocalized calculations. Energy
      decomposition analyses reveal specific dimeric contributions to exchange
      repulsion, charge delocalization, and dispersion. Since the wave functions for
      one-body and all two-body terms are variationally optimized in VMB2 and X-Pol, it
      is straightforward to obtain analytic gradient without the additional coupled
      perturbed Hartree-Fock step. Thus, the method can be useful for molecular
      dynamics simulations.

PMID- 22360229
TI  - Communication: translational Brownian motion for particles of arbitrary shape.
AB  - A single Brownian particle of arbitrary shape is considered. The time-dependent
      translational mean square displacement W(t) of a reference point at this particle
      is evaluated from the Smoluchowski equation. It is shown that at times larger
      than the characteristic time scale of the rotational Brownian relaxation, the
      slope of W(t) becomes independent of the choice of a reference point. Moreover,
      it is proved that in the long-time limit, the slope of W(t) is determined
      uniquely by the trace of the translational-translational mobility matrix MU(tt)
      evaluated with respect to the hydrodynamic center of mobility. The result is
      applicable to dynamic light scattering measurements, which indeed are performed
      in the long-time limit.

PMID- 22360230
TI  - Unraveling rotation-vibration mixing in highly fluxional molecules using
      diffusion Monte Carlo: applications to H3+ and H3O+.
AB  - A thorough examination of the use of fixed-node diffusion Monte Carlo for the
      study of rotation-vibration mixing in systems that undergo large amplitude
      vibrational motions is reported. Using H(3)(+) as a model system, the overall
      accuracy of the method is tested by comparing the results of these calculations
      with those from converged variational calculations. The effects of the presence
      of a large amplitude inversion mode on rotation-vibration mixing are considered
      by comparing the H(3)(+) results with those for H(3)O(+). Finally, analysis of
      the results of the fixed-node diffusion Monte Carlo calculations performed in
      different nodal regions is found to provide clear indications of when some of the
      methodology's underlying assumptions are breaking down as well as provide
      physical insights into the form of the rotation-vibration coupling that is most
      likely responsible.

PMID- 22360231
TI  - Bi-fidelity fitting and optimization.
AB  - A common feature in computations of chemical and physical properties is the
      investigation of phenomena at different levels of computational accuracy. Less
      accurate computations are used to provide a relatively quick understanding of the
      behavior of a system and allow a researcher to focus on regions of initial
      conditions and parameter space where interesting phenomena are likely to occur.
      These inexpensive calculations are often discarded when more accurate
      calculations are performed. This paper demonstrates how computations at different
      levels of accuracy can be simultaneously incorporated to study chemical and
      physical phenomena with less overall computational effort than the most expensive
      level of computation. A smaller set of computationally expensive calculations is
      needed because the set of expensive calculations is correlated with the larger
      set of less expensive calculations. We present two applications. First, we
      demonstrate how potential energy surfaces can be fit by simultaneously using
      results from two different levels of accuracy in electronic structure
      calculations. In the second application, we study the optical response of
      metallic nanostructures. The optical response is generated with calculations at
      two different grid resolutions, and we demonstrate how using these two levels of
      computation in a correlated fashion can more efficiently optimize the response.

PMID- 22360232
TI  - A generalized solid-state nudged elastic band method.
AB  - A generalized solid-state nudged elastic band (G-SSNEB) method is presented for
      determining reaction pathways of solid-solid transformations involving both
      atomic and unit-cell degrees of freedom. We combine atomic and cell degrees of
      freedom into a unified description of the crystal structure so that calculated
      reaction paths are insensitive to the choice of periodic cell. For the rock-salt
      to wurtzite transition in CdSe, we demonstrate that the method is robust for
      mechanisms dominated either by atomic motion or by unit-cell deformation;
      notably, the lowest-energy transition mechanism found by our G-SSNEB changes with
      cell size from a concerted transformation of the cell coordinates in small cells
      to a nucleation event in large cells. The method is efficient and can be applied
      to systems in which the force and stress tensor are calculated using density
      functional theory.

PMID- 22360233
TI  - A rare event sampling method for diffusion Monte Carlo using smart darting.
AB  - We identify a set of multidimensional potential energy surfaces sufficiently
      complex to cause both the classical parallel tempering and the guided or unguided
      diffusion Monte Carlo methods to converge too inefficiently for practical
      applications. The mathematical model is constructed as a linear combination of
      decoupled Double Wells [(DDW)(n)]. We show that the set (DDW)(n) provides a
      serious test for new methods aimed at addressing rare event sampling in
      stochastic simulations. Unlike the typical numerical tests used in these cases,
      the thermodynamics and the quantum dynamics for (DDW)(n) can be solved
      deterministically. We use the potential energy set (DDW)(n) to explore and
      identify methods that can enhance the diffusion Monte Carlo algorithm. We
      demonstrate that the smart darting method succeeds at reducing quasiergodicity
      for n ? 100 using just 1 * 10(6) moves in classical simulations (DDW)(n).
      Finally, we prove that smart darting, when incorporated into the regular or the
      guided diffusion Monte Carlo algorithm, drastically improves its convergence. The
      new method promises to significantly extend the range of systems computationally
      tractable by the diffusion Monte Carlo algorithm.

PMID- 22360234
TI  - Efficient simultaneous reverse Monte Carlo modeling of pair-distribution
      functions and extended x-ray-absorption fine structure spectra of crystalline
      disordered materials.
AB  - An efficient implementation of simultaneous reverse Monte Carlo (RMC) modeling of
      pair distribution function (PDF) and EXAFS spectra is reported. This
      implementation is an extension of the technique established by Krayzman et al.
      [J. Appl. Cryst. 42, 867 (2009)] in the sense that it enables simultaneous real
      space fitting of x-ray PDF with accurate treatment of Q-dependence of the
      scattering cross-sections and EXAFS with multiple photoelectron scattering
      included. The extension also allows for atom swaps during EXAFS fits thereby
      enabling modeling the effects of chemical disorder, such as migrating atoms and
      vacancies. Significant acceleration of EXAFS computation is achieved via
      discretization of effective path lengths and subsequent reduction of operation
      counts. The validity and accuracy of the approach is illustrated on small atomic
      clusters and on 5500-9000 atom models of bcc-Fe and alpha-Fe(2)O(3). The accuracy
      gains of combined simultaneous EXAFS and PDF fits are pointed out against PDF
      only and EXAFS-only RMC fits. Our modeling approach may be widely used in PDF and
      EXAFS based investigations of disordered materials.

PMID- 22360235
TI  - Approaching the bulk limit with finite cluster calculations using local
      increments: the case of LiH.
AB  - Finite-cluster calculations employing high-level wavefunction-based ab initio
      methods and extended atomic-orbital basis sets are used to determine local energy
      increments for bulk LiH. It is shown that these increments can be converged with
      respect to cluster size and point-charge embedding so as to yield bulk cohesive
      energies with an accuracy of better than 1 mE(h), both at the Hartree-Fock and at
      correlated levels. Instrumental for the efficiency of the scheme is the
      introduction of non-orthogonal orbitals, at an intermediate stage.

PMID- 22360236
TI  - Electronic states of cyclophanes with small bridges.
AB  - Electronic absorption and magnetic circular dichroism were recorded for five
      cyclophanes with ethano bridges: [2.2]paracyclophane, (1,2,4)[2.2.2]cyclophane,
      (1,2,4;1,2,5)[2.2.2]cyclophane, (1,2,3,4,5,6)(1,2,3,4,5,6)cyclophane, and trans
      [2.2]metacyclophane. Spectral and structural analyses were based on geometry
      optimization and calculations of transition energies, carried out using density
      functional theory methods. The assignments have been proposed for several
      electronic transitions observed in the region below 52,000 cm(-1). The
      observation of transitions which should be forbidden in the high D(2h) symmetry
      [2.2]paracyclophane suggests a twisted ground state structure of D(2) symmetry,
      although the former structure with large amplitude vibrations at room temperature
      cannot be excluded. The PBE0 functional turned out to appropriately reproduce the
      inter-ring distances and electronic transition energies.

PMID- 22360237
TI  - Scattering resonances in slow NH3-He collisions.
AB  - We theoretically study slow collisions of NH(3) molecules with He atoms, where we
      focus in particular on the observation of scattering resonances. We calculate
      state-to-state integral and differential cross sections for collision energies
      ranging from 10(-4) cm(-1) to 130 cm(-1), using fully converged quantum close
      coupling calculations. To describe the interaction between the NH(3) molecules
      and the He atoms, we present a four-dimensional potential energy surface, based
      on an accurate fit of 4180 ab initio points. Prior to collision, we consider the
      ammonia molecules to be in their antisymmetric umbrella state with angular
      momentum j = 1 and projection k = 1, which is a suitable state for Stark
      deceleration. We find pronounced shape and Feshbach resonances, especially for
      inelastic collisions into the symmetric umbrella state with j = k = 1. We analyze
      the observed resonant structures in detail by looking at scattering
      wavefunctions, phase shifts, and lifetimes. Finally, we discuss the prospects for
      observing the predicted scattering resonances in future crossed molecular beam
      experiments with a Stark-decelerated NH(3) beam.

PMID- 22360238
TI  - B80 and B101-103 clusters: remarkable stability of the core-shell structures
      established by validated density functionals.
AB  - Prompted by the very recent claim that the volleyball-shaped B(80) fullerene [X.
      Wang, Phys. Rev. B 82, 153409 (2010)] is lower in energy than the B(80) buckyball
      [N. G. Szwacki, A. Sadrzadeh, and B. I. Yakobson, Phys. Rev. Lett. 98, 166804
      (2007)] and core-shell structure [J. Zhao, L. Wang, F. Li, and Z. Chen, J. Phys.
      Chem. A 114, 9969 (2010)], and inspired by the most recent finding of another
      core-shell isomer as the lowest energy B(80) isomer [S. De, A. Willand, M.
      Amsler, P. Pochet, L. Genovese, and S. Goedecher, Phys. Rev. Lett. 106, 225502
      (2011)], we carefully evaluated the performance of the density functional methods
      in the energetics of boron clusters and confirmed that the core-shell
      construction (stuffed fullerene) is thermodynamically the most favorable
      structural pattern for B(80). Our global minimum search showed that both B(101)
      and B(103) also prefer a core-shell structure and that B(103) can reach the
      complete core-shell configuration. We called for great attention to the
      theoretical community when using density functionals to investigate boron-related
      nanomaterials.

PMID- 22360239
TI  - A femtosecond velocity map imaging study on B-band predissociation in CH3I. II.
      The 2(0)1 and 3(0)1 vibronic levels.
AB  - Femtosecond time-resolved velocity map imaging experiments are reported on
      several vibronic levels of the second absorption band (B-band) of CH(3)I,
      including vibrational excitation in the nu(2) and nu(3) modes of the bound
      (3)R(1)(E) Rydberg state. Specific predissociation lifetimes have been determined
      for the 2(0)(1) and 3(0)(1) vibronic levels from measurements of time-resolved
      I*((2)P(1/2)) and CH(3) fragment images, parent decay, and photoelectron images
      obtained through both resonant and non-resonant multiphoton ionization. The
      results are compared with our previously reported predissociation lifetime
      measurements for the band origin 0(0) (0) [Gitzinger et al., J. Chem. Phys. 132,
      234313 (2010)]. The result, previously reported in the literature, where
      vibrational excitation to the C-I stretching mode (nu(3)) of the CH(3)I
      (3)R(1)(E) Rydberg state yields a predissociation lifetime about four times
      slower than that corresponding to the vibrationless state, whereas
      predissociation is twice faster if the vibrational excitation is to the umbrella
      mode (nu(2)), is confirmed in the present experiments. In addition to the
      specific vibrational state lifetimes, which were found to be 0.85 +/- 0.04 ps and
      4.34 +/- 0.13 ps for the 2(0)(1) and 3(0)(1) vibronic levels, respectively, the
      time evolution of the fragment anisotropy and the vibrational activity of the
      CH(3) fragment are presented. Additional striking results found in the present
      work are the evidence of ground state I((2)P(3/2)) fragment production when
      excitation is produced specifically to the 3(0)(1) vibronic level, which is
      attributed to predissociation via the A-band (1)Q(1) potential energy surface,
      and the indication of a fast adiabatic photodissociation process through the
      repulsive A-band (3)A(1)(4E) state, after direct absorption to this state,
      competing with absorption to the 3(0)(1) vibronic level of the (3)R(1)(E) Rydberg
      state of the B-band.

PMID- 22360240
TI  - Structure and dynamics of the electronically excited C 1 and D 0+ states of ArXe
      from high-resolution vacuum ultraviolet spectra.
AB  - Vacuum ultraviolet spectra of the C 1 <- X 0(+) and D 0(+) <- X 0(+) band systems
      of ArXe have been recorded at high resolution. Analysis of the rotational
      structure of the spectra of several isotopomers, and in the case of Ar(129)Xe and
      Ar(131)Xe also of the hyperfine structure, has led to the derivation of a
      complete set of spectroscopic parameters for the C 1 and D 0(+) states. The
      rovibrational energy level structure of the C 1 state reveals strong homogeneous
      perturbations with neighboring Omega = 1 electronic states. The analysis of
      isotopic shifts led to a reassignment of the vibrational structure of the C 1
      state. The observation of electronically excited Xe fragments following
      excitation to the C state rotational levels of f parity indicates that the C
      state is predissociated by the electronic state of 0(-) symmetry associated with
      the Ar((1)S(0)) + Xe(6s(')[1/2](0) (o)) dissociation limit. The observed
      predissociation dynamics differ both qualitatively and quantitatively from the
      behavior reported in previous investigations. An adiabatic two-state coupling
      model has been derived which accounts for the irregularities observed in the
      rovibronic and hyperfine level structure of the C 1 state. The model predicts the
      existence of a second state of Omega = 1 symmetry, supporting several
      tunneling/predissociation resonances located ~200 cm(-1) above the C 1 state.

PMID- 22360241
TI  - Recoil frame photoelectron angular distributions of BF3: a sensitive probe of the
      shape resonance in the F 1s continuum.
AB  - Recoil frame photoelectron angular distributions (RFPADs) of BF(3) molecules are
      presented over the energy region of the shape resonance in the F 1s continuum.
      Time-dependent density functional theory calculations are also given to
      understand the shape resonance dynamics. The RFPADs have been compared with the
      theoretical calculations. It is found that the RFPADs calculated by the localized
      core-hole model are in better agreement with the experimental, compared with
      those by the delocalized core hole. Dipole matrix elements and dipole prepared
      continuum wavefunctions show that the shape resonance in the F 1s ionization
      continuum of BF(3) is induced by p-partial waves as previously reported by
      Swanson et al. [J. Chem. Phys. 75, 619 (1981)]. However, due to the couplings
      with the other partial waves the feature characteristic of the p-partial waves
      has not been observed in the RFPADs.

PMID- 22360242
TI  - A fresh look at dense hydrogen under pressure. I. an introduction to the problem,
      and an index probing equalization of H-H distances.
AB  - In the first of a series of four papers on hydrogen under pressure, and its
      transitions from an initiating molecular state, we begin by defining carefully
      the problem, and setting the distance scale of interactions of protons and
      electrons in molecular aggregates of the first of the elements. Following a
      review of the experimental situation, in particular the phase diagram of
      hydrogen, in as much as it is known, and the behavior of its vibrons and rotons,
      we move onto the setting up of a numerical laboratory for probing the underlying
      physics and chemistry of interactions in hydrogen as the pressure increases. The
      laboratory consists of the preferred static structures emerging from calculations
      on the system in the range of 1 atm to 500 GPa, those of Pickard and Needs. The
      intermolecular (inter-pair) H...H separations naturally decrease with increasing
      pressure, first rapidly so, then more slowly. The intramolecular (intra-pair) H-H
      distances vary over a much smaller scale (0.05 A) as the pressure increases,
      first decreasing, then increasing, and finally decreasing. We define an
      equalization function to gauge the approach to equality of the first neighbor and
      shortest next neighbor H (proton) separations in this numerical laboratory. And
      we find that metallization is likely to occur before bond equalization.

PMID- 22360243
TI  - A fresh look at dense hydrogen under pressure. II. Chemical and physical models
      aiding our understanding of evolving H-H separations.
AB  - In order to explain the intricate dance of intramolecular (intra-proton-pair) H-H
      separations observed in a numerical laboratory of calculationally preferred
      static hydrogen structures under pressure, we examine two effects through
      discrete molecular models. The first effect, we call it physical, is of simple
      confinement. We review a salient model already in the literature, that of LeSar
      and Herschbach, of a hydrogen molecule in a spheroidal cavity. As a complement,
      we also study a hydrogen molecule confined along a line between two helium atoms.
      As the size of the cavity/confining distance decreases (a surrogate for
      increasing pressure), in both models the equilibrium proton separation decreases
      and the force constant of the stretching vibration increases. The second effect,
      which is an orbital or chemical factor, emerges from the electronic structure of
      the known molecular transition metal complexes of dihydrogen. In these the H-H
      bond is significantly elongated (and the vibron much decreased in frequency) as a
      result of depopulation of the sigma(g) bonding molecular orbital of H(2), and
      population of the antibonding sigma(u)* MO. The general phenomenon, long known in
      chemistry, is analyzed through a specific molecular model of three hydrogen
      molecules interacting in a ring, a motif found in some candidate structures for
      dense hydrogen.

PMID- 22360244
TI  - A fresh look at dense hydrogen under pressure. III. Two competing effects and the
      resulting intra-molecular H-H separation in solid hydrogen under pressure.
AB  - A preliminary discussion of the general problem of localization of wave
      functions, and the way it is approached in theoretical condensed matter physics
      (Wannier functions) and theoretical chemistry (localized or fragment orbitals) is
      followed by an application of the ideas of Paper II in this series to the
      structures of hydrogen as they evolve under increasing pressure. The idea that
      emerges is that of simultaneously operative physical (reduction of available
      space by an increasingly stiff wall of neighboring molecules) and chemical
      (depopulation of the sigma(g) bonding molecular orbital of H(2), and population
      of the antibonding sigma(u)* MO) factors. The two effects work in the same
      direction of reducing the intermolecular separation as the pressure increases,
      but compete, working in opposite directions, in their effect on the
      intramolecular (nearest neighbor, intra-pair) distance. We examine the population
      of sigma(g) and sigma(u)* MOs in our numerical laboratory, as well as the total
      electron transfer (small), and polarization (moderate, where allowed by symmetry)
      of the component H(2) molecules. From a molecular model of two interacting H(2)
      molecules we find a linear relationship between the electron transfer from
      sigma(g) to sigma(u)* of a hydrogen molecular fragment and the intramolecular H-H
      separation, and that, in turn, allows us to estimate the expected bond lengths in
      H(2) under pressure if the first effect (that of simple confinement) was absent.
      In essence, the intramolecular H-H separations under pressure are much shorter
      than they would be, were there no physical/confinement effect. We then use this
      knowledge to understand how the separate E and PV terms contribute to hydrogen
      phase changes with increasing pressure.

PMID- 22360245
TI  - A fresh look at dense hydrogen under pressure. IV. Two structural models on the
      road from paired to monatomic hydrogen, via a possible non-crystalline phase.
AB  - In this paper, we examine the transition from a molecular to monatomic solid in
      hydrogen over a wide pressure range. This is achieved by setting up two models in
      which a single parameter delta allows the evolution from a molecular structure to
      a monatomic one of high coordination. Both models are based on a cubic Bravais
      lattice with eight atoms in the unit cell; one belongs to space group Pa3, the
      other to space group R3m. In Pa3 one moves from effective 1-coordination, a
      molecule, to a simple cubic 6-coordinated structure but through a very special
      point (the golden mean is involved) of 7-coordination. In R3m, the evolution is
      from 1 to 4 and then to 3 to 6-coordinate. If one studies the enthalpy as a
      function of pressure as these two structures evolve (delta increases), one sees
      the expected stabilization of minima with increased coordination (moving from 1
      to 6 to 7 in the Pa3 structure, for instance). Interestingly, at some specific
      pressures, there are in both structures relatively large regions of phase space
      where the enthalpy remains roughly the same. Although the structures studied are
      always higher in enthalpy than the computationally best structures for solid
      hydrogen - those emerging from the Pickard and Needs or McMahon and Ceperley
      numerical laboratories - this result is suggestive of the possibility of a
      microscopically non-crystalline or "soft" phase of hydrogen at elevated
      pressures, one in which there is a substantial range of roughly equi-enthalpic
      geometries available to the system. A scaling argument for potential dynamic
      stabilization of such a phase is presented.

PMID- 22360246
TI  - The structure of liquid N-methyl pyrrolidone probed by x-ray scattering and
      molecular simulations.
AB  - The structural properties of liquid N-methyl pyrrolidone have been investigated
      by combining energy dispersive x-ray diffraction experiments and molecular
      dynamics simulations with generalized AMBER force field. A very good agreement
      between theoretical and experimental diffraction patterns was achieved. The
      analysis of the radial distribution functions shows that the methyl-carbonyl H
      bond network observed in the crystal structure is partly preserved in the liquid
      structure.

PMID- 22360247
TI  - Two-point approximation to the Kramers problem with coloured noise.
AB  - We present a method, founded on previous renewal approaches as the classical
      Wilemski-Fixman approximation, to describe the escape dynamics from a potential
      well of a particle subject to non-Markovian fluctuations. In particular, we show
      how to provide an approximated expression for the distribution of escape times if
      the system is governed by a generalized Langevin equation (GLE). While we show
      that the method could apply to any friction kernel in the GLE, we focus here on
      the case of power-law kernels, for which extensive literature has appeared in the
      last years. The method presented (termed as two-point approximation) is able to
      fit the distribution of escape times adequately for low potential barriers, even
      if conditions are far from Markovian. In addition, it confirms that non
      exponential decays arise when a power-law friction kernel is considered (in
      agreement with related works published recently), which questions the existence
      of a characteristic reaction rate in such situations.

PMID- 22360248
TI  - Microscopic probing of the size dependence in hydrophobic solvation.
AB  - We report small angle x-ray scattering data demonstrating the direct experimental
      microscopic observation of the small-to-large crossover behavior of hydrophobic
      effects in hydrophobic solvation. By increasing the side chain length of
      amphiphilic tetraalkyl-ammonium (C(n)H(2n+1))(4)N(+) (R(4)N(+)) cations in
      aqueous solution we observe diffraction peaks indicating association between
      cations at a solute size between 4.4 and 5 A, which show temperature dependence
      dominated by hydrophobic attraction. Using O K-edge x-ray absorption we show that
      small solutes affect hydrogen bonding in water similar to a temperature decrease,
      while large solutes affect water similar to a temperature increase. Molecular
      dynamics simulations support, and provide further insight into, the origin of the
      experimental observations.

PMID- 22360249
TI  - Rotational dynamics of benzene and water in an ionic liquid explored via
      molecular dynamics simulations and NMR T1 measurements.
AB  - The rotational dynamics of benzene and water in the ionic liquid (IL) 1-butyl-3
      methylimidazolium chloride are studied using molecular dynamics (MD) simulation
      and NMR T(1) measurements. MD trajectories based on an effective potential are
      used to calculate the (2)H NMR relaxation time, T(1) via Fourier transform of the
      relevant rotational time correlation function, C(2R)(t). To compensate for the
      lack of polarization in the standard fixed-charge modeling of the IL, an
      effective ionic charge, which is smaller than the elementary charge is employed.
      The simulation results are in closest agreement with NMR experiments with respect
      to the temperature and Larmor frequency dependencies of T(1) when an effective
      charge of +/-0.5e is used for the anion and the cation, respectively. The
      computed C(2R)(t) of both solutes shows a bi-modal nature, comprised of an
      initial non-diffusive ps relaxation plus a long-time ns tail extending to the
      diffusive regime. Due to the latter component, the solute dynamics is not under
      the motional narrowing condition with respect to the prevalent Larmor frequency.
      It is shown that the diffusive tail of the C(2R)(t) is most important to
      understand frequency and temperature dependencies of T(1) in ILs. On the other
      hand, the effect of the initial ps relaxation is an increase of T(1) by a
      constant factor. This is equivalent to an "effective" reduction of the
      quadrupolar coupling constant (QCC). Thus, in the NMR T(1) analysis, the
      rotational time correlation function can be modeled analytically in the form of
      aexp (-t/tau) (Lipari-Szabo model), where the constant a, the Lipari-Szabo
      factor, contains the integrated contribution of the short-time relaxation and tau
      represents the relaxation time of the exponential (diffusive) tail. The Debye
      model is a special case of the Lipari-Szabo model with a = 1, and turns out to be
      inappropriate to represent benzene and water dynamics in ILs since a is as small
      as 0.1. The use of the Debye model would result in an underestimation of the QCC
      by a factor of 2-3 as a compensation for the neglect of the Lipari-Szabo factor.

PMID- 22360250
TI  - Molecular dynamics approach to water structure of H(II) mesophase of monoolein.
AB  - The goal of the present work is to study theoretically the structure of water
      inside the water cylinder of the inverse hexagonal mesophase (H(II)) of glyceryl
      monooleate (monoolein, GMO), using the method of molecular dynamics. To simplify
      the computational model, a fixed structure of the GMO tube is maintained. The non
      standard cylindrical geometry of the system required the development and
      application of a novel method for obtaining the starting distribution of water
      molecules. A predictor-corrector schema is employed for generation of the initial
      density of water. Molecular dynamics calculations are performed at constant
      volume and temperature (NVT ensemble) with 1D periodic boundary conditions
      applied. During the simulations the lipid structure is kept fixed, while the
      dynamics of water is unrestrained. Distribution of hydrogen bonds and density as
      well as radial distribution of water molecules across the water cylinder show the
      presence of water structure deep in the cylinder (about 6 A below the GMO heads).
      The obtained results may help understanding the role of water structure in the
      processes of insertion of external molecules inside the GMO/water system. The
      present work has a semi-quantitative character and it should be considered as the
      initial stage of more comprehensive future theoretical studies.

PMID- 22360251
TI  - Crystal nucleation and the solid-liquid interfacial free energy.
AB  - We present the results of molecular dynamics simulation of crystal nucleation in
      a supercooled Lennard-Jones liquid. Temperature and baric dependences of the
      nucleation rate, the Zeldovich factor, nucleus size diffusion coefficient, the
      radius, and the pressure in a critical crystal nucleus are defined in computer
      simulation. The data obtained have been used in the framework of classical
      nucleation theory to calculate the effective surface energy of crystal nuclei
      gamma(e). It is shown that the value of gamma(e) at T = const exceeds the value
      of the interfacial free energy at a flat crystal-liquid interface gamma(infinity)
      and gamma(e) < gamma(infinity) at p = const.

PMID- 22360252
TI  - Theory and simulations of quantum glass forming liquids.
AB  - A comprehensive microscopic dynamical theory is presented for the description of
      quantum fluids as they transform into glasses. The theory is based on a quantum
      extension of mode-coupling theory. Novel effects are predicted, such as reentrant
      behavior of dynamical relaxation times. These predictions are supported by path
      integral ring polymer molecular dynamics simulations. The simulations provide
      detailed insight into the factors that govern slow dynamics in glassy quantum
      fluids. Connection to other recent work on both quantum glasses as well as
      quantum optimization problems is presented.

PMID- 22360253
TI  - Kinetic criteria of glass formation and the pressure dependence of the glass
      transition temperature.
AB  - An overview on different attempts of formulation of kinetic criteria of glass
      formation is given. It is analyzed which of the characteristic time scales-time
      of observation, time of relaxation, and time of change of external parameters
      have to be employed to appropriately develop such criteria. Based on this
      analysis, a general model-independent kinetic criterion for glass formation is
      formulated. As a first consequence, it is shown that it is not-as often claimed
      the Deborah number which governs glass formation. Based on this general kinetic
      criterion for glass formation, general expressions for the dependence of the
      glass transition temperature on pressure (and vice versa) are obtained being
      essentially ratios of the partial derivatives of the appropriate relaxation times
      with respect to pressure and temperature, respectively. Employing, as examples,
      further two different (free volume and entropy based) models for the description
      of viscous flow and relaxation, respectively, relations similar but, in general,
      not identical to the classical Ehrenfest relations describing second-order
      equilibrium phase transitions are obtained. In this way, it can be explained why
      one of the Ehrenfest's relations is usually fulfilled in glass transition and the
      other not and why the Prigogine-Defay ratio in glass transition is not equal to
      one as this is the case with Ehrenfest's ratio in second-order equilibrium phase
      transitions.

PMID- 22360254
TI  - Quantitative interpretation of the very fast electronic relaxation of most Ln3+
      ions in dissolved complexes.
AB  - In a reference frame rigidly bound to the complex, we consider two Hamiltonians
      possibly at the origin of the very fast electronic relaxation of the paramagnetic
      lanthanide Ln(3+) ions (Ln = Ce to Nd, Tb to Yb), namely the mean (static) ligand
      field Hamiltonian and the transient ligand-field Hamiltonian. In the laboratory
      frame, the bombardment of the complex by solvent molecules causes its Brownian
      rotation and its vibration-distorsion dynamics governing the fluctuations of the
      static and transient terms, respectively. These fluctuations are at the origin of
      electronic relaxation. The electronic relaxation of a Ln(3+) ion is defined by
      the decays of the time correlation functions (TCFs) of the longitudinal and
      transverse components of the total angular momentum J of its ground multiplet.
      The Brownian rotation of the complex and its vibration-distorsion dynamics are
      simulated by random walks, which enable us to compute the TCFs from first
      principles. It is shown that the electronic relaxation is governed mainly by the
      magnitude of the transient ligand-field, and not by its particular expression.
      The range of expected values of this ligand-field together with the lower limit
      of relaxation time enforced by the values of the vibration-distortion correlation
      time in liquids give rise to effective electronic relaxation times which are in
      satisfactory overall agreement with the experimental data. In particular, these
      considerations explain why the electronic relaxation times vary little with the
      coordinating ligand and are practically independent of the external field
      magnitude.

PMID- 22360255
TI  - Viscosity of liquid mixtures: the Vesovic-Wakeham method for chain molecules.
AB  - New expressions for the viscosity of liquid mixtures, consisting of chain-like
      molecules, are derived by means of Enskog-type analysis. The molecules of the
      fluid are modelled as chains of equally sized, tangentially joined, and rigid
      spheres. It is assumed that the collision dynamics in such a fluid can be
      approximated by instantaneous collisions. We determine the molecular size
      parameters from the viscosity of each pure species and show how the different
      effective parameters can be evaluated by extending the Vesovic-Wakeham (VW)
      method. We propose and implement a number of thermodynamically consistent mixing
      rules, taking advantage of SAFT-type analysis, in order to develop the VW method
      for chain molecules. The predictions of the VW-chain model have been compared in
      the first instance with experimental viscosity data for octane-dodecane and
      methane-decane mixtures, thus, illustrating that the resulting VW-chain model is
      capable of accurately representing the viscosity of real liquid mixtures.

PMID- 22360256
TI  - Experimental evidence for excess entropy discontinuities in glass-forming
      solutions.
AB  - Glass transition temperatures T(g) are investigated in aqueous binary and multi
      component solutions consisting of citric acid, calcium nitrate (Ca(NO(3))(2)),
      malonic acid, raffinose, and ammonium bisulfate (NH(4)HSO(4)) using a
      differential scanning calorimeter. Based on measured glass transition
      temperatures of binary aqueous mixtures and fitted binary coefficients, the T(g)
      of multi-component systems can be predicted using mixing rules. However, the
      experimentally observed T(g) in multi-component solutions show considerable
      deviations from two theoretical approaches considered. The deviations from these
      predictions are explained in terms of the molar excess mixing entropy difference
      between the supercooled liquid and glassy state at T(g). The multi-component
      mixtures involve contributions to these excess mixing entropies that the mixing
      rules do not take into account.

PMID- 22360257
TI  - Pt on graphene monolayers supported on a Ni(111) substrate: relativistic density
      functional calculations.
AB  - The structural, energetic, and magnetic properties of Pt atoms and dimers
      adsorbed on a Ni-supported graphene layer have been investigated using density
      functional calculations, including the influence of dispersion forces and of spin
      orbit coupling. Dispersion forces are found to be essential to stabilize a
      chemisorbed graphene layer on the Ni(111) surface. The presence of the Ni
      substrate leads not only to a stronger interaction of Pt atoms and dimers with
      graphene but also to a locally increased binding between graphene and the
      substrate and a complex reconstruction of the adlayer. The stronger binding of
      the dimer also stabilizes a flat adsorption geometry in contrast to the upright
      geometry on a free-standing graphene layer. These effects are further enhanced by
      dispersion corrections. Isolated Pt adatoms and flat dimers are found to be non
      magnetic, while an upright Pt dimer has strongly anisotropic spin and orbital
      moments. For the clean C/Ni(111) system, we calculate an in-plane magnetic
      anisotropy, which is also conserved in the presence of isolated Pt adatoms.
      Surprisingly, upright Pt-dimers induce a re-orientation of the easy magnetic axis
      to a direction perpendicular to the surface, in analogy to Pt(2) on a free
      standing graphene layer and to the axial anisotropy of a gas-phase Pt(2) dimer.

PMID- 22360258
TI  - Excluded volume effects in macromolecular forces and ion-interface interactions.
AB  - A charged Yukawa liquid confined in a slit nanopore is studied in order to
      understand excluded volume effects in the interaction force between the pore
      walls. A previously developed self-consistent scheme [S. Buyukdagli, C. V. Achim,
      and T. Ala-Nissila, J. Stat. Mech. 2011, P05033] and a new simpler variational
      procedure that self-consistently couple image forces, surface charge induced
      electric field, and pore modified core interactions are used to this aim. For
      neutral pores, it is shown that with increasing pore size, the theory predicts a
      transition of the interplate pressure from an attractive to a strongly repulsive
      regime associated with an ionic packing state, an effect observed in previous
      Monte Carlo simulations for hard core charges. We also establish the mean-field
      theory of the model and show that for dielectrically homogeneous pores, the mean
      field regime of the interaction between the walls corresponds to large pores of
      size d > 4 A. The role of the range of core interactions in the ionic rejection
      and interplate pressure is thoroughly analyzed. We show that the physics of the
      system can be split into two screening regimes. The ionic packing effect takes
      place in the regime of moderately screened core interactions characterized with
      the bare screening parameter of the Yukawa potential b ? 3/l(B), where l(B) is
      the Bjerrum length. In the second regime of strongly screened core interactions b
      ? 3/l(B), solvation forces associated with these interactions positively
      contribute to the ionic rejection driven by electrostatic forces and enhance the
      magnitude of the attractive pressure. For weakly charged pores without a
      dielectric discontinuity, core interactions make a net repulsive contribution to
      the interplate force and also result in oscillatory pressure curves, whereas for
      intermediate surface charges, these interactions exclusively strengthen the
      external pressure, thereby reducing the magnitude of the net repulsive interplate
      force. The pronounced dependence of the interplate pressure and ionic partition
      coefficients on the magnitude and the range of core interactions indicates
      excluded volume effects as an important ion specificity and a non-negligible
      ingredient for the stability of macromolecules in electrolyte solutions.

PMID- 22360259
TI  - Phase segregation of a symmetric diblock copolymer in constrained space with a
      square-pillar array.
AB  - In this study, we apply a self-consistent field theory of polymers to study the
      structures of a symmetric diblock copolymer in parallel substrates filled with
      square-pillar arrays in which the substrates and pillars exhibit a weak
      preference for one block of the copolymer. Three classes of structures, i.e.,
      lamellae, perpendicular cylinders, and bicontinuous structures, are achieved by
      varying the polymer film thickness, the pillar pitch (the distance between two
      centers of the nearest neighboring pillars), the gap and rotation of the pillars.
      Because of the confinement along horizontal directions imposed by the pillar
      array, eight novel types of perpendicular lamellar structures and eight novel
      types of cylindrical structures with various shapes and distributions occur. In
      the hybridization states of the parallel and perpendicular lamellar structures,
      several novel bicontinuous structures such as the double-cylinder network, pseudo
      lamellae, and perforated lamellar structure are also found. By comparing the free
      energies of the various possible structures, the antisymmetric parallel lamellae
      are observed to be stable with the larger pillar gap at a certain film thickness.
      The structural transformations between the alternating cylindrical structures
      (alternating cross-shaped, square-shaped, and octagonal perpendicular cylinders)
      and parallel lamellae with increasing film thickness or pillar gap are well
      explained by the modified strong separation theory. Our results indicate that
      array confinement can be an effective method to prepare novel polymeric
      nanopattern structures.

PMID- 22360260
TI  - Effects of bending and torsion rigidity on deformation and breakage of flexible
      fibers: a direct simulation study.
AB  - To understand the various mechanisms of fiber deformation of flexible fiber
      suspensions, we carry out a direct simulation study to analyze the effect of
      fiber rigidity on fiber motion in simple shear flow. Such a study may be used to
      investigate the critical parameters controlling the breakage of flexible fibers
      during processing. We model the fiber as a series of rigid spheres connected by
      stiff springs. The stretching, bending, and torsional rigidities are determined
      by Young's modulus and shear modulus to realistically model the fiber rigidity.
      The model correctly predicts the orbit period of fiber rotation, T gamma, as well
      as the trend of critical flow strength, eta gamma/E, versus fiber aspect ratio,
      r(p), at which breakage occurs in simple shear flow.

PMID- 22360261
TI  - Self-propelled motion of a fluid droplet under chemical reaction.
AB  - We study self-propelled dynamics of a droplet due to a Marangoni effect and
      chemical reactions in a binary fluid with a dilute third component of chemical
      product which affects the interfacial energy of a droplet. The equation for the
      migration velocity of the center of mass of a droplet is derived in the limit of
      an infinitesimally thin interface. We found that there is a bifurcation from a
      motionless state to a propagating state of droplet by changing the strength of
      the Marangoni effect.

PMID- 22360263
TI  - Far-infrared spectroscopy on free-standing protein films under defined
      temperature and hydration control.
AB  - The functionality of proteins is governed by their dynamics. We have performed a
      systematic investigation on four different proteins in the far-infrared spectral
      region under control of the two external parameters that have the strongest
      influence on the dynamics, namely temperature and hydration. The absorption
      measurements covering the frequency range from 40 cm(-1) to 690 cm(-1) (1-20 THz)
      close the gap between the well-studied mid-infrared and the recent THz
      investigations. By preparing the proteins as free-standing films, we achieve
      unprecedented reproducibility. Besides a featureless slope in the THz range, we
      can identify absorption peaks characteristic for each protein and others common
      to several proteins. We fit the spectra to extract the peak positions and suggest
      assignments for them. The far-infrared absorption spectra of all proteins are
      basically independent on hydration. By a detailed analysis of the sorption
      isotherms this can be explained by the low absorption of biological water, which
      resembles more the behavior of ice than that of liquid water.

PMID- 22360262
TI  - Electron stimulated desorption of anions from native and brominated single
      stranded oligonucleotide trimers.
AB  - We measured the low energy electron stimulated desorption (ESD) of anions from
      thin films of native (TXT) and bromine monosubstituted (TBrXT) oligonucleotide
      trimers deposited on a gold surface (T = thymidine, X = T, deoxycytidine (C),
      deoxyadenosine (A) or deoxyguanosine (G), Br = bromine). The desorption of H(-),
      CH(3)(-)/NH(-), O(-)/NH(2)(-), OH(-), CN(-), and Br(-) was induced by 0 to 20 eV
      electrons. Dissociative electron attachment, below 12 eV, and dipolar
      dissociation, above 12 eV, are responsible for the formation of these anions. The
      comparison of the results obtained for the native and brominated trimers suggests
      that the main pathways of TBrXT degradation correspond to the release of the
      hydride and bromide anions. Significantly, the presence of bromine in
      oligonucleotide trimers blocks the electron-induced degradation of nuclobases as
      evidenced by a dramatic decrease in CN(-) desorption. An increase in the yields
      of OH(-) is also observed. The debromination yield of particular oligonucleotides
      diminishes in the following order: BrdU > BrdA > BrdG > BrdC. Based on these
      results, 5-bromo-2(')-deoxyuridine appears to be the best radiosensitizer among
      the studied bromonucleosides.

PMID- 22360264
TI  - Note: the role of external electric fields in enhancing ion mobility, drift
      velocity, and drift-diffusion rates in aqueous electrolyte solutions [J. Chem.
      Phys. 134, 114504 (2011)].
AB  - The effect of external electric fields on enhancing ion mobility, drift velocity,
      and drift diffusion as a function of solution concentration has been investigated
      using molecular dynamics simulations. Our results show that the unusual nonlinear
      behavior observed when the solution concentration matches seawater is also
      observed when the concentration is reduced to half of that value. These results
      are of significance in designing processes for desalinating seawater using
      electro-deionization in which the concentration would decrease during salt
      removal, and for purification of brackish waters which also have lower salt
      content.

PMID- 22360266
TI  - DoGeNetS: using optimisation to discriminate regulatory network topologies based
      on gene expression data.
AB  - Gene regulatory networks (GRNs) determine the dynamics of gene expression.
      Interest often focuses on the topological structure of a GRN while numerical
      parameters (e.g. decay rates) are unknown and less important. For larger GRNs,
      inference of structure from gene expression data is prohibitively difficult.
      Models are often proposed based on integrative interpretation of multiple sources
      of information. We have developed DoGeNetS (Discrimination of Gene Network
      Structures), a method to directly assess candidate models of GRN structure
      against a target gene expression data set. The transsys language serves to model
      GRN structures. Numeric parameters are optimised to approximate the target data.
      Multiple restarts of optimisation yield score sets that provide a basis to
      statistically discriminate candidate models according to their potential to
      explain the target data. We demonstrate discrimination power of the DoGeNetS
      method by relating structural divergence to divergence between gene expression
      data sets. Known models are used to generate target expression data, and a set of
      candidate models with a defined structural divergence to the true model is
      produced. Structural divergence and divergence of expression profiles after
      optimisation are strongly correlated. We further show that discrimination is
      possible at noise levels exceeding those typical of contemporary microarray data.
      DoGeNetS is capable of discriminating the best GRN structure from among a small
      number of candidates. p values indicate whether differences in divergence of
      expression are significant. Although this study uses single gene knockouts, the
      DoGeNetS method can be adapted to simulate a virtually unlimited range of
      experimental conditions. [Includes supplementary material].

PMID- 22360267
TI  - Optimal ratio of scaffold complex to free Fus3 to maximise the accumulation of
      phosphorylated Fus3 in yeast pheromone signalling pathway.
AB  - In this study, the author considers the design rule of the intracellular
      signalling pathway. In yeast pheromone signalling pathway, scaffold Ste5 tethers
      the components of signalling pathway, Ste11, Ste7 and Fus3. Even though scaffold
      complex is independently produced before stimuli, excessively expressed Fus3 as
      compared with scaffold exists in cytoplasm as free kinase. How the ratio of
      scaffold complex to the free Fus3 is determined is not clear yet. First, the
      contribution of free Fus3 to signal transduction is theoretically shown by using
      a simplified model of pheromone signalling pathway. Next, the optimum expression
      levels of Ste5, Ste11, Ste7 and Fus3 are systematically explored by using the
      detailed model and genetic algorithm under the constraint that the total
      expression level of these four genes is limited. Excessive expression of Fus3 is
      advantageous for the efficient signalling without stall of the signal
      transduction. The result suggests that the component of signalling pathway is
      optimally expressed to maximise the accumulation of phosphorylated Fus3 at a
      fixed time point under the constraint that the total gene expression is limited.
      The proposed model provides further insight into the signalling network from the
      point of view of not only its function but also its optimality.

PMID- 22360268
TI  - Network-based analysis of complex diseases.
AB  - Complex diseases are commonly believed to be caused by the breakdown of several
      correlated genes rather than individual genes. The availability of genome-wide
      data of high-throughput experiments provides us with new opportunity to explore
      this hypothesis by analysing the disease-related biomolecular networks, which are
      expected to bridge genotypes and disease phenotypes and further reveal the
      biological mechanisms of complex diseases. In this study, the authors review the
      existing network biology efforts to study complex diseases, such as breast
      cancer, diabetes and Alzheimer's disease, using high-throughput data and
      computational tools. Specifically, the authors categorise these existing methods
      into several classes based on the research topics, that is, disease genes,
      dysfunctional pathways, network signatures and drug-target networks. The authors
      also summarise the pros and cons of those methods from both computation and
      application perspectives, and further discuss research trends and future topics
      of this promising field.

PMID- 22360270
TI  - When will we ever learn? A case in support of a new relationship with remote
      living Australians.

PMID- 22360269
TI  - MEF2 is regulated by CaMKIIdelta2 and a HDAC4-HDAC5 heterodimer in vascular
      smooth muscle cells.
AB  - VSMCs (vascular smooth muscle cells) dedifferentiate from the contractile to the
      synthetic phenotype in response to acute vascular diseases such as restenosis and
      chronic vascular diseases such as atherosclerosis, and contribute to growth of
      the neointima. We demonstrated previously that balloon catheter injury of rat
      carotid arteries resulted in increased expression of CaMKII (Ca(2+)/calmodulin
      dependent protein kinase) IIdelta(2) in the medial wall and the expanding
      neointima [House and Singer (2008) Arterioscler. Thromb. Vasc. Biol. 28, 441
      447]. These findings led us to hypothesize that increased expression of
      CaMKIIdelta(2) is a positive mediator of synthetic VSMCs. HDAC (histone
      deacetylase) 4 and HDAC5 function as transcriptional co-repressors and are
      regulated in a CaMKII-dependent manner. In the present paper, we report that
      endogenous HDAC4 and HDAC5 in VSMCs are activated in a Ca(2+)- and CaMKIIdelta(2)
      dependent manner. We show further that AngII (angiotensin II)- and PDGF (platelet
      derived growth factor)-dependent phosphorylation of HDAC4 and HDAC5 is reduced
      when CaMKIIdelta(2) expression is suppressed or CaMKIIdelta(2) activity is
      attenuated. The transcriptional activator MEF2 (myocyte-enhancer factor 2) is an
      important determinant of VSMC phenotype and is regulated in an HDAC-dependent
      manner. In the present paper, we report that stimulation of VSMCs with ionomycin
      or AngII potentiates MEF2's ability to bind DNA and increases the expression of
      established MEF2 target genes Nur77 (nuclear receptor 77) (NR4A1) and MCP1
      (monocyte chemotactic protein 1) (CCL2). Suppression of CaMKIIdelta(2) attenuates
      increased MEF2 DNA-binding activity and up-regulation of Nur77 and MCP1. Finally,
      we show that HDAC5 is regulated by HDAC4 in VSMCs. Suppression of HDAC4
      expression and activity prevents AngII- and PDGF-dependent phosphorylation of
      HDAC5. Taken together, these results illustrate a mechanism by which
      CaMKIIdelta(2) mediates MEF2-dependent gene transcription in VSMCs through
      regulation of HDAC4 and HDAC5.

PMID- 22360271
TI  - A novel familial variation of the thyroid hormone receptor beta gene (I276N)
      associated with resistance to thyroid hormone.

PMID- 22360272
TI  - General intellectual impairment in chronic right hemisphere damaged patients with
      anosognosia: a group study.
AB  - The study evaluates the possible relations between cognitive impairment,
      persisting anosognosia for hemiplegia and peripersonal neglect. Thirty eight
      chronic right hemisphere stroke patients were divided in three age- and education
      matched groups: A (n = 13) patients with left hemiparesis, peripersonal neglect,
      and anosognosia for hemiplegia; B (n = 12) patients with left hemiparesis and
      peripersonal neglect, and C (n = 13) patients with left hemiparesis only. We used
      MMSE and WAIS Verbal IQ and verbal subtests to assess cognitive impairment in
      patients, in order to avoid a bias due to visuospatial deficit, which is common
      in patients with neglect. VIQ, Information, Digit Span and Vocabulary WAIS
      subtests as well as MMSE were found to be significantly lower in group A versus
      group B. No difference was found in any test between groups B and C, indicating a
      general worse cognition in patients compared to those without anosognosia for
      hemiplegia. Patients with anosognosia for hemiplegia also showed larger brain
      lesions and, more frequently, frontal, parietal, temporal and basal ganglia
      involvement, particularly if they had low verbal IQ, indicating a relationship
      between cognitive impairment, persisting anosognosia for hemiplegia and large
      right hemisphere lesions.

PMID- 22360273
TI  - Nutraceuticals and botanicals: overview and perspectives.
AB  - The discovery, development and marketing of food supplements, nutraceuticals and
      related products are currently the fastest growing segments of the food industry.
      Functional foods can be considered part or borderline to these products and may
      be defined as foods or food ingredients that have additional health or
      physiological benefits over and above the normal nutritional value they provide.
      This trend is driven by several factors, mainly due to the current consumer
      perceptions: the first and dominant being 'Natural is good', and other secondary,
      such as the increasing cost of many pharmaceuticals and their negative secondary
      effects, the insistent marketing campaign, the increasing perception of the need
      of a healthy diet and its importance in the health and homeostasis organism
      conditions. However, the central point is that nutraceuticals, botanicals and
      other herbal remedies, including the entry of new functional foods, are important
      because of their acceptance as the novel and modern forms to benefit of natural
      substances. Due to the rapid expansion in this area, the development of several
      aspects is considered as it could influence the future of the market of these
      products negatively: an imbalance existing between the increasing number of
      claims and products on the one hand, the development of policies to regulate
      their application and safety on the other, rapid and valuable controls to check
      the composition, including the plant extracts or adulteration to improve
      efficacy, like the presence of synthetic drugs. It is interesting to see that,
      from the negative factors reported by the market analysts, a change in consumers
      preferences is absent. The functional properties of many plant extracts, in
      particular, are being investigated for potential use as novel nutraceuticals and
      functional foods. Although the availability of scientific data is rapidly
      improving, the central aspect concerns the validation of these products. The
      first step of this crucial aspect is the security of the composition, obtained by
      the useful and adapted analytical approach. On the other hand, in the first
      instance, security is assured by the millenary use as food of the great majority
      of these plants. The importance and the novelty of functional food are inherent
      in the possibility to renew the secure use of plants to maintain healthiness of
      man in novel forms of use adapted to modern times. The market of 'other
      substances', after the emergence of the first period of enthusiastic explosion,
      is entering into the maturation period, with three important arguments to face:
      (a) security in composition, production and sale, avoiding easy conversions or
      convenient approaches and favouring competence and professionalism, (b)
      definition of influence of metabolic aspects, including scientific validation and
      (c) regulatory aspects, e.g. the claims definition and relative influences. The
      last aspect seams to be in primis the most crucial and fundamental to the future
      of all the sectors. The role of European Food and Safety Authority (EFSA) in the
      EU market must be considered and consequences if negative decisions on 'other
      substances' claim will be adopted in each country's legislation.

PMID- 22360274
TI  - What should be in a self-management programme for people with early dementia?
AB  - OBJECTIVES: First, to use participative research methods to obtain views from
      people with dementia and carers about their experiences and the interventions
      that they consider can assist in facilitating independence and quality of life
      post diagnosis. Second, to use these views to identify priority topics for a
      potential self-management programme. Third, to explore the relevance of the
      identified topics with a consultation group of people with dementia and their
      carers, thus informing the creation of a draft self-management programme. METHOD:
      A series of individual and dyad interviews were conducted with people with
      dementia and family carers to explore their experiences post diagnosis and obtain
      views of how quality life can be maintained while living with dementia. A further
      group of people with dementia and carers then met over six successive weeks to
      explore and provide feedback on the topic areas generated out of the initial
      interviews and add to the content. RESULTS: Data generated from the individual
      interviews identified a number of themes for a potential self-management group
      which were then validated through consultation. Optimum modes of delivery of a
      self-management programme were also indicated. CONCLUSIONS: A draft programme has
      been constructed building upon the framework of identified priorities. The
      process and outputs from the consultation also indicated the significant
      ramifications of such a programme for services.

PMID- 22360275
TI  - Encoding and recognition after traumatic brain injury: neuropsychological and
      functional magnetic resonance imaging findings.
AB  - Although impairment of episodic memory is common after traumatic brain injury
      (TBI), the complex nature of human memory suggests the need to study more than
      recall alone. For this reason, we are presenting an extension with additional
      analyses of persons reported in a previous publication ( Russell, Arenth,
      Scanlon, Kessler, & Ricker, 2011 ). We examined both the encoding and recognition
      components of an episodic memory paradigm containing both word and letter string
      blocks using functional magnetic resonance imaging (fMRI) and neuropsychological
      testing. This paradigm was completed by 12 persons with complicated mild,
      moderate, or severe TBI and 12 matched uninjured controls. Comparisons were made
      between groups and stimulus types. While task behavioral performance was not
      significantly different between groups, imaging results showed greater activation
      for the TBI group during the encoding portion of the task, while the control
      group exhibited more activation on the recognition portion. Observed areas of
      activation suggest that the TBI group may have used a less effective, but more
      automatic verbal strategy for encoding the nonpronounceable letter strings, while
      controls may have opted for more of a recognition-focused strategy. Group
      differences in California Verbal Learning Test-Second Edition (CVLT-II)
      performance supported these ideas, and further neuropsychological testing also
      suggested limitations in executive functioning in the TBI group that may have
      influenced performance. Implications for intervention are discussed.

PMID- 22360276
TI  - Glycopolypeptides with a redox-triggered helix-to-coil transition.
AB  - Conformation-switchable glycopolypeptides were prepared by the living
      polymerization of glycosylated L-cysteine-N-carboxyanhydride (glyco-C NCA)
      monomers. These new monomers were prepared in high yield by coupling of alkene
      terminated C-linked glycosides of D-galactose or D-glucose to L-cysteine using
      thiol-ene "click" chemistry, followed by their conversion to the corresponding
      glyco-C NCAs. The resulting glycopolypeptides were found to be water-soluble and
      alpha-helical in solution. Aqueous oxidation of the side-chain thioether linkages
      in these polymers to sulfone groups resulted in disruption of the alpha-helical
      conformations without loss of water solubility. The ability to switch chain
      conformation and remain water-soluble is unprecedented in synthetic polymers, and
      allows new capabilities to control presentation of sugar functionality in subtly
      different contexts.

PMID- 22360277
TI  - Lupane-type pentacyclic triterpenes in Langmuir monolayers: a synchrotron
      radiation scattering study.
AB  - Lupane-type pentacyclic triterpenes (lupeol, betulin, and betulinic acid) are
      natural products isolated from various plant sources. The terpenes exhibit a vast
      spectrum of biological activity and are applied in therapies for different
      diseases, among which the anticancer, anti-HIV, antihypercholesteremic, and
      antiinflammatory are the most promising. These chemicals possess amphiphilic
      structure and were proved to interact strongly with biomembranes, which can be
      the key stage in their mechanism of action. In our studies, we applied Langmuir
      monolayers as versatile models of biomembranes. It turned out that the three
      investigated terpenes are capable of stable monolayer formation; however, these
      monolayers differ profoundly regarding their physicochemical characteristics. In
      our research, we applied the Langmuir technique (surface pressure-mean molecular
      area (pi-A) isotherm registration) coupled with Brewster angle microscopy (BAM),
      but the main focus was on the synchrotron radiation scattering method, grazing
      incidence X-ray diffraction (GIXD), which provides information on the amphiphilic
      molecule ordering in the angstrom scale. It was proved that all the investigated
      terpenes form crystalline phases in their monolayers. In the case of lupeol, only
      the closely packed upright phase was observed, whereas for betulin and betulinic
      acid, the phase situation was more complex. Betulinic acid molecules can be
      organized in an upright phase, which is crystalline, and in a tilted phase, which
      is amorphous. The betulin film is a conglomerate of an upright crystalline
      monolayer phase, tilted amorphous monolayer phase, and a crystalline tilted
      bilayer. In our paper, we discuss the factors leading to the formation of the
      observed phases and the implications of our results to the therapeutic
      applications of the native lupane-type triterpenes.

PMID- 22360278
TI  - Professional editors or scientist editors? Both perspectives have value.

PMID- 22360279
TI  - Nitric oxide regulation of cyclic di-GMP synthesis and hydrolysis in Shewanella
      woodyi.
AB  - Although several reports have documented nitric oxide (NO) regulation of biofilm
      formation, the molecular basis of this phenomenon is unknown. In many bacteria,
      an H-NOX (heme-nitric oxide/oxygen-binding) gene is found near a diguanylate
      cyclase (DGC) gene. H-NOX domains are conserved hemoproteins that are known NO
      sensors. It is widely recognized that cyclic di-GMP (c-di-GMP) is a ubiquitous
      bacterial signaling molecule that regulates the transition between motility and
      biofilm. Therefore, NO may influence biofilm formation through H-NOX regulation
      of DGC, thus providing a molecular-level explanation for NO regulation of biofilm
      formation. This work demonstrates that, indeed, NO-bound H-NOX negatively affects
      biofilm formation by directly regulating c-di-GMP turnover in Shewanella woodyi
      strain MS32. Exposure of wild-type S. woodyi to a nanomolar level of NO resulted
      in the formation of thinner biofilms, and less intracellular c-di-GMP, than in
      the absence of NO. Also, a mutant strain in the gene encoding SwH-NOX showed a
      decreased level of biofilm formation (and a decreased amount of intracellular c
      di-GMP) with no change observed upon NO addition. Furthermore, using purified
      proteins, it was demonstrated that SwH-NOX and SwDGC are binding partners. SwDGC
      is a dual-functioning DGC; it has diguanylate cyclase and phosphodiesterase
      activities. These data indicate that NO-bound SwH-NOX enhances c-di-GMP
      degradation, but not synthesis, by SwDGC. These results support the biofilm
      growth data and indicate that S. woodyi senses nanomolar NO with an H-NOX domain
      and that SwH-NOX regulates SwDGC activity, resulting in a reduction in c-di-GMP
      concentration and a decreased level of biofilm growth in the presence of NO.
      These data provide a detailed molecular mechanism for NO regulation of c-di-GMP
      signaling and biofilm formation.

PMID- 22360280
TI  - Application of phylogenetic microarray analysis to discriminate sources of fecal
      pollution.
AB  - Conventional methods for fecal source tracking typically use single biomarkers to
      systematically identify or exclude sources. High-throughput DNA sequence analysis
      can potentially identify all sources of microbial contaminants in a single test
      by measuring the total diversity of fecal microbial communities. In this study,
      we used phylogenetic microarray analysis to determine the comprehensive suite of
      bacteria that define major sources of fecal contamination in coastal California.
      Fecal wastes were collected from 42 different populations of humans, birds, cows,
      horses, elk, and pinnipeds. We characterized bacterial community composition
      using a DNA microarray that probes for 16S rRNA genes of 59,316 different
      bacterial taxa. Cluster analysis revealed strong differences in community
      composition among fecal wastes from human, birds, pinnipeds, and grazers.
      Actinobacteria, Bacilli, and many Gammaproteobacteria taxa discriminated birds
      from mammalian sources. Diverse families within the Clostridia and Bacteroidetes
      taxa discriminated human wastes, grazers, and pinnipeds from each other. We found
      1058 different bacterial taxa that were unique to either human, grazing mammal,
      or bird fecal wastes. These OTUs can serve as specific identifier taxa for these
      sources in environmental waters. Two field tests in marine waters demonstrate the
      capacity of phylogenetic microarray analysis to track multiple sources with one
      test.

PMID- 22360282
TI  - Structural and spectroscopic study of the LiRb molecule beyond the Born
      Oppenheimer approximation.
AB  - Adiabatic and diabatic potential energy curves and the permanent and transition
      dipole moments of the low-lying electronic states of the LiRb molecule
      dissociating into Rb(5s, 5p, 4d, 6s, 6p, 5d, 7s, 6d) + Li(2s, 2p) have been
      investigated. The molecular calculations are performed with an ab initio approach
      based on nonempirical pseudopotentials for Rb(+) and Li(+) cores, parametrized l
      dependent core polarization potentials and full configuration interaction
      calculations. The derived spectroscopic constants (R(e), D(e), T(e), omega(e),
      omega(e)x(e), and B(e)) of the ground state and lower excited states are in good
      agreement with the available theoretical works. However, the 8-10(1)Sigma(+), 8
      10(3)Sigma(+), 6(1,3)Pi, and 3(1,3)Delta excited states are studied for the first
      time. In addition, to the potential energy, accurate permanent and transition
      dipole moments have been determined for a wide interval of internuclear
      distances. The permanent dipole moment of LiRb has revealed ionic characters both
      relating to electron transfer and yielding Li(-)Rb(+) and Li(+)Rb(-)
      arrangements. The diabatic potential energy for the (1,3)Sigma(+), (1,3)Pi, and
      (1,3)Delta symmetries has been performed for this molecule for the first time.
      The diabatization method is based on variational effective Hamiltonian theory and
      effective metric, where the adiabatic and diabatic states are connected by an
      appropriate unitary transformation.

PMID- 22360283
TI  - Functional analysis of an anaerobic m-xylene-degrading enrichment culture using
      protein-based stable isotope probing.
AB  - A sulfate-reducing consortium maintained for several years in the laboratory with
      m-xylene as sole source of carbon and energy was characterized by terminal
      restriction fragment length polymorphism (T-RFLP) fingerprinting of PCR-amplified
      16S rRNA genes and stable isotope probing of proteins (Protein-SIP). During
      growth upon m-xylene or methyl-labeled m-xylene (1,3-dimethyl-(13)C(2)-benzene),
      a phylotype affiliated to the family Desulfobacteriaceae became most abundant. A
      second dominant phylotype was affiliated to the phylum Epsilonproteobacteria. In
      cultures grown with methyl-labeled m-xylene, 331 proteins were identified by LC
      MS/MS analysis. These proteins were either not (13)C-labeled (23%) or showed a
      (13)C-incorporation of 19-22 atom% (13)C (77%), the latter demonstrating that
      methyl groups of m-xylene were assimilated. (13)C-labeled proteins were involved
      in anaerobic m-xylene biodegradation, in sulfate reduction, in the Wood-Ljungdahl
      pathway, and in general housekeeping functions. Thirty-eight percent of the
      labeled proteins were affiliated to Deltaproteobacteria. Probably due to a lack
      of sequence data from Epsilonproteobacteria, only 14 proteins were assigned to
      this phylum. Our data suggest that m-xylene is assimilated by the
      Desulfobacteriaceae phylotype, whereas the role of the Epsilonproteobacterium in
      the consortium remained unclear.

PMID- 22360284
TI  - Synthesis, photophysical, photochemical, and computational studies of coumarin
      labeled nicotinamide derivatives.
AB  - The syntheses and photophysical/photochemical properties of two amide-tethered
      coumarin-labeled nicotinamides are described. Photochemical studies of 6-bromo-7
      hydroxycoumarin-4-ylmethylnicotinamide (BHC-nicotinamide) revealed an unexpected
      solvent effect. This result is rationalized by computational studies of the
      different protonation states using TD-DFT with the M06L/6-311+G** method with
      implicit and explicit solvation models. Molecular orbital energies responsible
      for the lambda(max) excitation show that the functionalization of the coumarin
      ring results in a strong red-shift from 330 to 370 nm when the pH of solution is
      increased from 3.06 to 8.07. From this MO analysis, a model for solvent
      interactions has been proposed. The BHC-nicotinamide proved to be photochemically
      stable, which is also interpreted in terms of NBO calculations. The results
      provide a set of principles for the rational design of either photostable
      labeling reagents or photolabile cage compounds.

PMID- 22360285
TI  - Relationship between TWIST expression and epithelial-mesenchymal transition of
      oesophageal squamous cell carcinoma.
AB  - We have investigated mRNA and protein expression of TWIST, Vimentin and E
      cadherin in ESCC (oesophageal squamous cell carcinoma) and explored their
      relationship with tumour's infiltration and metastasis. RT-PCR (reverse
      transcriptase-PCR) was used to evaluate mRNA expression of TWIST, E-cadherin and
      Vimentin in 40 cases of ESCC. The protein expression of the genes was examined by
      immunohistochemical staining in each specimen. Expression of TWIST, E-cadherin
      and Vimentin mRNA and protein with clinicopathologic parameters were analysed.
      mRNAs of TWIST, Vimentin and E-cadherin were expressed in 75, 55 and 35%
      respectively of ESCC, i.e. significantly different from that in normal
      oesophageal mucosa (15, 0 and 85% respectively; P<0.01). In ESCC with LN (lymph
      node) metastasis, expression of TWIST and Vimentin mRNA, but not E-cadherin mRNA
      was significantly higher (100 and 83%) than in ESCC without LN metastasis (64 and
      43%, P=0.018) respectively. Levels of mRNA expression of the 3 genes followed
      similar patterns to their above-mentioned frequencies. Protein expression of
      TWIST, E-cadherin and Vimentin were observed in 70, 35 and 50% respectively of
      ESCC, which were significantly different from normal mucosa (15, 80 and 0%;
      P<0.001). In ESCC with LN metastasis, protein expression of TWIST and Vimentin,
      but not E-cadherin, were significantly higher (100 and 75%) than in ESCC without
      LN metastasis (61 and 39%). Protein expression of TWIST was positively correlated
      with Vimentin (r=0.327, P=0.039), but negatively correlated with E-cadherin (r= 
      0.633, P=0.000). Thus, both mRNAs and proteins of TWIST and Vimentin were
      significantly overexpressed in ESCC, especially ESCC with LN metastasis. The mRNA
      and protein of E-cadherin were down-regulated in ESCC. These results suggest
      potential roles of TWIST as the promoter of tumour invasion and metastasis
      associated with down-regulation of E-cadherin.

PMID- 22360286
TI  - A chemically-responsive nanojunction within a silver nanowire.
AB  - The formation of a nanometer-scale chemically responsive junction (CRJ) within a
      silver nanowire is described. A silver nanowire was first prepared on glass using
      the lithographically patterned nanowire electrodeposition method. A 1-5 nm gap
      was formed in this wire by electromigration. Finally, this gap was reconnected by
      applying a voltage ramp to the nanowire resulting in the formation of a
      resistive, ohmic CRJ. Exposure of this CRJ-containing nanowire to ammonia (NH(3))
      induced a rapid (<30 s) and reversible resistance change that was as large as
      DeltaR/R(0) = (+)138% in 7% NH(3) and observable down to 500 ppm NH(3). Exposure
      to water vapor produced a weaker resistance increase of DeltaR/R(0,H(2)O) = (+)10
      15% (for 2.3% water) while nitrogen dioxide (NO(2)) exposure induced a stronger
      concentration-normalized resistance decrease of DeltaR/R(0,NO(2)) = (-)10-15%
      (for 500 ppm NO(2)). The proposed mechanism of the resistance response for a CRJ,
      supported by temperature-dependent measurements of the conductivity for CRJs and
      density functional theory calculations, is that semiconducting p-type Ag(x)O is
      formed within the CRJ and the binding of molecules to this Ag(x)O modulates its
      electrical resistance.

PMID- 22360287
TI  - Isolation of Cunninghamella blakesleeana in an immunodepressed patient.

PMID- 22360288
TI  - The care dependency scale for measuring basic human needs: an international
      comparison.
AB  - AIM: To report a study conducted to compare the utility of the care dependency
      scale across four countries. BACKGROUND: The care dependency scale provides a
      framework for assessing the needs of institutionalized patients for nursing care.
      Henderson's components of nursing care have been used to specify the variable
      aspects of the concept of care dependency and to develop the care dependency
      scale items. DESIGN: The study used a cross-cultural survey design. METHOD:
      Patients were recruited from four different countries: Japan, The Netherlands,
      Poland and Turkey. In each of the participating countries, basic human needs were
      assessed by nurses using a translated version of the original Dutch care
      dependency scale. Psychometric properties in terms of reliability and validity of
      the care dependency scale have been assessed using Cronbach's alpha, Guttman's
      lambda-2, inter-item correlation and principal components analysis. Data were
      collected in 2008 and 2009. RESULTS: High internal consistency values were
      demonstrated. Principal component analysis confirmed the one-factor model
      reported in earlier studies. CONCLUSION: Outcomes confirm Henderson's idea that
      human needs are fundamental appearing in every patient-nurse relationship,
      independent of the patient's age, the type of care setting and/or cultural
      background. The psychometric characteristics of the care dependency scale make
      this instrument very useful for comparative research across countries.

PMID- 22360289
TI  - Molecular modeling on pyrimidine-urea inhibitors of TNF-alpha production: an
      integrated approach using a combination of molecular docking, classification
      techniques, and 3D-QSAR CoMSIA.
AB  - Molecular docking, classification techniques, and 3D-QSAR CoMSIA were combined in
      a multistep framework with the ultimate goal of identifying potent pyrimidine
      urea inhibitors of TNF-alpha production. Using the crystal structure of p38alpha,
      all the compounds were docked into the enzyme active site. The docking pose of
      each compound was subsequently used in a receptor-based alignment for the
      generation of the CoMSIA fields. "Active" and "inactive" compounds were used to
      build a Random Tree classification model using the docking score and the CoMSIA
      fields as input parameters. Domain of applicability indicated the compounds for
      which activity estimations can be accepted with confidence. For the active
      compounds, a 3D-QSAR CoMSIA model was subsequently built to accurately estimate
      the IC(50) values. This novel multistep framework gives insight into the
      structural characteristics that affect the binding and the inhibitory activity of
      these analogues on p38alpha MAP kinase, and it can be extended to other classes
      of small-molecule inhibitors. In addition, the simplicity of the proposed
      approach provides expansion to its applicability such as in virtual screening
      procedures.

PMID- 22360291
TI  - Research priorities in biomarkers and surrogate end-points.
AB  - Ideal tests of the effects of therapeutic interventions measure the desired
      outcomes; however, the desired outcomes are not always easily measured or may be
      long-term objectives. Biomarkers and surrogate end-points are often cheaper and
      easier to measure and can be measured over a shorter time span. They can be used
      in screening, diagnosing, staging, and monitoring diseases, in monitoring
      responses to interventions, and in various aspects of drug discovery and
      development. They can be extrinsic to the body or intrinsic, and can relate to
      any point in the pharmacological chain, at the molecular, cellular, tissue, or
      organ level. Problems arise when the relation between the pathophysiology of the
      disease and the mechanism of action of the intervention is not properly
      understood; when adverse effects obviate therapeutic effects; when confounding
      factors, such as other drugs, alter the surrogate independently of the final end
      point; when a biomarker persists after resolution of the disease; and when the
      concentration-effect curves for the effects of an intervention on the primary
      outcome and the surrogate are different. Use of biomarkers may also be hindered
      by poor reproducibility of measurement techniques. Challenges for clinical
      pharmacologists are to devise biomarker tests that are reliable, reproducible,
      sensitive, and specific, and surrogate end-points that are associated with the
      clinical outcomes of concern and useful. A robust taxonomy is needed of the
      relations that link the pathophysiology of disease, the mechanisms of action of
      interventions and their adverse effects, the desired clinical outcomes, and the
      surrogate end-points that predict them.

PMID- 22360290
TI  - Immune responses induced by heterologous boosting of recombinant bacillus
      Calmette-Guerin with Ag85B-ESAT6 fusion protein in levamisole-based adjuvant.
AB  - In the present study, we evaluated the effectiveness of a levamisole-based
      adjuvant (ADL) to enhance the ability of the Ag85B-ESAT6 fusion protein to boost
      immune responses after primary vaccination with recombinant bacillus Calmette
      Guerin (rBCG) in Balb/c mice. The results were compared with that of the control
      adjuvant formulation of dimethyl dioctadecylammonium bromide (DDA) and
      monophosphoryl lipid A (MPL), which has previously been shown to induce T-helper
      type 1 (Th1)-biased responses. Enzyme-linked immunospot (ELISPOT) assay with
      Ag85B and ESAT6 derived peptides corresponding to CD4+ and CD8+ T cell restricted
      epitopes and cell surface immunostaining indicated that Ag85B-ESAT6/ADL
      predominantly triggered activation of CD4+ T cells. Functional CD8+ T cells with
      interferon (IFN)-gamma production or cytotoxicity were undetectable all
      vaccinated mice. The ADL adjuvant modified T-helper (Th) subtypes by up
      regulating multiple signature cytokines. Furthermore, profiles of the
      immunoglobulin G (IgG) subtypes indicated ADL enhanced the secretion of Th1
      associated IgG2a antibodies and decreased the yield of Th2-associated IgG1
      subtype. These observations suggest that the ADL adjuvant formulated with a
      protein booster may induce Th1-biased cellular and humoral immune responses to
      primary vaccination with a live attenuated bacterial TB vaccine.

PMID- 22360292
TI  - Evaluating care pathways for community psychiatry in England: a qualitative
      study.
AB  - OBJECTIVES: In view of forthcoming 'payment by results' (PbR) for mental health,
      increasing number of National Health Service (NHS) Trusts are reorganizing their
      community services for working age adults to create care pathways. However,
      research base for the care pathways model in mental health is limited. Our NHS
      Foundation Trust was one of the first to introduce care pathways for community
      psychiatry in the UK. We have carried out a qualitative study to evaluate how
      this model works out in practice, including its impact on quality of patient
      care, mental health professionals and primary care. METHODS: We interviewed
      doctors, multidisciplinary staff and Trusts managers (19 in total). Transcripts
      of recorded interviews were coded and analysed thematically using a grounded
      theory approach. RESULTS: Overall, despite teething problems, working in pathways
      was generally seen as a positive change. It led to more focused interventions
      being offered, and practitioners being held to account over clear standards of
      care. It is more cost-effective and allows for active case management and clear
      clinical leadership. It is recovery focused and encourages social inclusion. The
      arbitrary time frame, strict criteria and thresholds for different teams can
      create issues. Improved communication, flexible and patient-centred approach,
      staff supervision, and increasing support to primary care were felt to be central
      to this model working efficiently and effectively. CONCLUSIONS: Introduction of
      care pathways is an important step towards effective implementation of PbR for
      mental health. Our study would inform future research into care pathways,
      facilitate organizational learning and help to improve effectiveness of services.

PMID- 22360293
TI  - Potential therapeutic effects of oral bisphosphonates on the intestine.
AB  - Bisphosphonates are the principal drugs prescribed for the prevention of
      osteoporotic fractures. They are bone specific but poorly absorbed. In oral
      formulations, almost 99% of the administered dose remains within the intestinal
      tract and reaches the small and large bowel. Although the nitrogen-containing
      bisphosphonates can irritate the distal esophageal/gastric mucosa, they improve
      drug-induced colitis in animal models and exhibit antitumor properties on
      intestinal cells in vitro. Several recent epidemiological studies provide
      evidence of a reduced risk of colorectal cancer in osteoporotic patients treated
      with oral bisphosphonates, notably alendronate. In this review, we will explore
      the possible mechanisms of action underlying these effects and raise the question
      of whether these agents might be used in the chemoprophylaxis against colorectal
      cancer.

PMID- 22360294
TI  - A brief history on the oscillating roles of thalamus and cortex in absence
      seizures.
AB  - This review summarizes the findings obtained over the past 70 years on the
      fundamental mechanisms underlying generalized spike-wave (SW) discharges
      associated with absence seizures. Thalamus and cerebral cortex are the brain
      areas that have attracted most of the attention from both clinical and
      experimental researchers. However, these studies have often favored either one or
      the other structure in playing a major role, thus leading to conflicting
      interpretations. Beginning with Jasper and Penfield's topistic view of absence
      seizures as the result of abnormal functions in the so-called centrencephalon, we
      witness the naissance of a broader concept that considered both thalamus and
      cortex as equal players in the process of SW discharge generation. Furthermore,
      we discuss how recent studies have identified fine changes in cortical and
      thalamic excitability that may account for the expression of absence seizures in
      naturally occurring genetic rodent models and knockout mice. The end of this
      fascinating tale is presumably far from being written. However, I can confidently
      conclude that in the unfolding of this "novel," we have discovered several
      molecular, cellular, and pharmacologic mechanisms that govern forebrain
      excitability, and thus consciousness, during the awake state and sleep.

PMID- 22360295
TI  - Role of outer membrane c-type cytochromes MtrC and OmcA in Shewanella oneidensis
      MR-1 cell production, accumulation, and detachment during respiration on
      hematite.
AB  - The iron-reducing bacterium Shewanella oneidensis MR-1 has the capacity to
      contribute to iron cycling over the long term by respiring on crystalline iron
      oxides such as hematite when poorly crystalline phases are depleted. The ability
      of outer membrane cytochromes OmcA and MtrC of MR-1 to bind to and transfer
      electrons to hematite has led to the suggestion that they function as terminal
      reductases when this mineral is used as a respiratory substrate. Differences in
      their redox behavior and hematite-binding properties, however, indicate that they
      play different roles in the electron transfer reaction. Here, we investigated how
      these differences in cytochrome behavior with respect to hematite affected
      biofilm development when the mineral served as terminal electron acceptor (TEA).
      Upon attachment to hematite, cells of the wild-type (WT) strain as well as those
      of a DeltaomcA mutant but not those of a DeltamtrC mutant replicated and
      accumulated on the mineral surface. The results indicate that MtrC but not OmcA
      is required for growth when this mineral serves as TEA. While an OmcA deficiency
      did not impede cell replication and accumulation on hematite prior to achievement
      of a maximum surface cell density comparable to that established by WT cells,
      OmcA was required for efficient electron transfer and cell attachment to hematite
      once maximum surface cell density was achieved. OmcA may therefore play a role in
      overcoming barriers to electron transfer and cell attachment to hematite imposed
      by reductive dissolution of the mineral surface from cell respiration associated
      with achievement of high surface cell densities.

PMID- 22360296
TI  - Predictors and consequences of perceived lack of choice in becoming an informal
      caregiver.
AB  - OBJECTIVES: Using data from a national sample of informal caregivers to older
      adults, we identify predictors of lack of choice and the consequences of lack of
      choice in taking on the caregiving role. METHODS: A national telephone survey
      with 1397 caregivers was carried out to assess whether respondents had a choice
      in taking on the caregiving role, their demographic characteristics, the nature
      and duration of their caregiving experience, and its impact on their physical and
      psychological well-being. We compare caregivers who felt they had no choice in
      taking on the caregiving role to those who did. RESULTS: In total, 44% of
      caregivers reported a lack of choice in taking on the caregiving role. Highly
      educated, older caregivers caring for a younger care recipient with emotional or
      behavioral problems were most likely to report that they had no choice in taking
      on the caregiving role. Lack of choice is associated with higher levels of
      emotional stress, physical strain, and negative health impacts, after controlling
      for multiple confounds including level of care provided, relationship type,
      primary health condition of the care recipient, and demographic characteristics.
      CONCLUSION: Lack of choice is an independent risk factor for the negative effects
      of caregiving, and clinicians should be vigilant to lack of choice as a marker of
      caregiver distress.

PMID- 22360297
TI  - Use of serum biomarkers to predict cerebral hypoxia after severe traumatic brain
      injury.
AB  - The management of severe traumatic brain injury (TBI) focuses on prevention and
      treatment of secondary insults such as cerebral hypoxia (CH). There are a number
      of biomarkers that are thought to play a part in secondary injury following
      severe TBI. This study evaluates the association between S100beta, neuron
      specific enolase (NSE), and glial fibrillary acidic protein (GFAP), detected in
      the serum of severe TBI patients and CH as measured by brain tissue oxygen
      partial pressure (Pbo(2)). Patients with severe TBI were prospectively enrolled.
      Pressure times time (PTD; mm Hg*h), measuring the depth and duration of CH, was
      calculated for 12-h periods for episodes of moderate (Pbo(2) < 20 mm Hg) and
      severe (Pbo(2) < 15 mm Hg) CH, and compared to serum levels of S100beta, NSE, and
      GFAP drawn prior to periods of monitoring. An adjusted mixed model analysis was
      applied as was receiver operating characteristic (ROC) curve analysis. Of 76
      patients enrolled, 24 had Pbo(2) monitoring. One hundred and thirty serum samples
      were matched with 12-h periods of monitoring. Significant associations were found
      in adjusted analyses between increasing serum levels of S100beta
      (coefficient=0.57, 0.56; p<0.001), NSE (coefficient=0.48, 0.52; p<0.001), and
      GFAP (coefficient=0.29, 0.30; p=0.003 and 0.002), and increasing PTD of moderate
      (Pbo(2)<20 mm Hg) and severe (Pbo(2)<15 mm Hg) CH. AUCs for the prediction of
      moderate and severe CH were 0.62 and 0.66 for S100beta, 0.55 and 0.71 for NSE,
      and 0.50 and 0.62 for GFAP, respectively. Specificities were between 76% and 90%
      for S100beta and NSE. S100beta, NSE, and GFAP demonstrate promise as candidate
      serum markers of impending CH. The fact that these biomarker elevations occur
      prior to the onset of clinical manifestations suggests that we may be able to
      predict imminent events following TBI. Given the morbidity of CH, early
      intervention and prevention may have a significant impact on outcomes and help
      guide decisions about the timing of interventions.

PMID- 22360298
TI  - Effect of the inclination of a maxillary central incisor on periodontal stress:
      finite element analysis.
AB  - OBJECTIVE: To determine the effect of labiolingual inclination of a maxillary
      central incisor on the magnitude and distribution of stresses within the
      periodontal space. MATERIALS AND METHODS: Five three-dimensional finite element
      models of a right maxillary central incisor were created with 0 degrees , 10
      degrees , 20 degrees , 30 degrees , and 40 degrees  inclination. Each incisor
      model was subjected to a 1 N lingual-directed force and 6-12 N.mm countertipping
      moment on the labial surface. The stress level within the periodontal ligament
      was calculated in terms of maximum principal stresses. RESULTS: With increased
      inclination, compressive stresses tended to increase whereas tensile stresses
      tended to decrease. The location where compressive stress was prevalent changed
      from the midroot area to the apical area on the lingual side, while the area
      where tensile stresses were predominant changed from the midroot area to the
      cervical area on the labial side. CONCLUSION: There are more compressive stresses
      concentrated at the apex of incisors with a high degree of inclination than in
      incisors that are more upright. This may be associated with the higher clinical
      incidence of apical root resorption found in inclined maxillary central incisors.

PMID- 22360300
TI  - Rheological study of physical cross-linked quaternized cellulose hydrogels
      induced by beta-glycerophosphate.
AB  - As a weak base, beta-glycerophosphate (beta-GP) was used to spontaneously
      initiate gelation of quaternized cellulose (QC) solutions at body temperature.
      The QC/beta-GP solutions are flowable below or at room temperature but gel
      rapidly under physiological conditions. In order to clarify the sol-gel
      transition process of the QC/beta-GP systems, the complex was investigated by
      dynamic viscoelastic measurements. The shear storage modulus (G') and loss
      modulus (G") as a function of (1) concentration of beta-GP (c(beta-GP)), (2)
      concentration of QC (c(QC)), (3) degree of substitution (DS; i.e., the average
      number of substituted hydroxyl groups in the anhydroglucose unit) of QC, (4)
      viscosity-average molecular weight (M(eta)) of QC, and (5) solvent medium were
      studied by the oscillatory rheology. The sol-gel transition temperature of
      QC/beta-GP solutions decreased with an increase of c(QC) and c(beta-GP), the
      M(eta) of QC, and a decrease of the DS of QC and pH of the solvent. The sol-gel
      transition temperature and time could be easily controlled by adjusting the
      concentrations of QC and beta-GP, M(eta) and DS of QC, and the solvent medium.
      Gels formed after heating were irreversible; i.e., after cooling to lower
      temperature they could not be dissolved to become liquid again. The aggregation
      and entanglement of QC chains, electrostatic interaction, and hydrogen bonding
      between QC and beta-GP were the main factors responsible for the irreversible sol
      gel transition behavior of QC/beta-GP systems.

PMID- 22360301
TI  - Induction of pH sensitivity on the fluorescence lifetime of quantum dots by NIR
      fluorescent dyes.
AB  - Modulation of the fluorescence lifetime (FLT) of CdTeSe/ZnS quantum dots (QDs) by
      near-IR (NIR) organic chromophores represents a new strategy for generating
      reproducible pH-sensing nanomaterials. The hybrid construct transfers the pH
      sensitivity of photolabile NIR cyanine dyes to highly emissive and long-lifetime
      pH-insensitive QDs, thereby inducing a reproducible FLT change from 29 ns at pH
      >7 to 12 ns at pH <5. This approach provides an unparalleled large dynamic FLT
      range for pH sensing at NIR wavelengths.

PMID- 22360302
TI  - Heterogeneity of intracellular polymer storage states in enhanced biological
      phosphorus removal (EBPR)--observation and modeling.
AB  - A number of agent-based models (ABMs) for biological wastewater treatment
      processes have been developed, but their skill in predicting heterogeneity of
      intracellular storage states has not been tested against observations due to the
      lack of analytical methods for measuring single-cell intracellular properties.
      Further, several mechanisms can produce and maintain heterogeneity (e.g.,
      different histories, uneven division) and their relative importance has not been
      explored. This article presents an ABM for the enhanced biological phosphorus
      removal (EBPR) treatment process that resolves heterogeneity in three
      intracellular polymer storage compounds (i.e., polyphosphate,
      polyhydroxybutyrate, and glycogen) in three functional microbial populations
      (i.e., polyphosphate-accumulating, glycogen-accumulating, and ordinary
      heterotrophic organisms). Model predicted distributions were compared to those
      based on single-cell estimates obtained using a Raman microscopy method for a
      laboratory-scale sequencing batch reactor (SBR) system. The model can reproduce
      many features of the observed heterogeneity. Two methods for introducing
      heterogeneity were evaluated. First, biological variability in individual cell
      behavior was simulated by randomizing model parameters (e.g., maximum acetate
      uptake rate) at division. This method produced the best fit to the data. An
      optimization algorithm was used to determine the best variability (i.e.,
      coefficient of variance) for each parameter, which suggests large variability in
      acetate uptake. Second, biological variability in individual cell states was
      simulated by randomizing state variables (e.g., internal nutrient) at division,
      which was not able to maintain heterogeneity because the memory in the internal
      states is too short. These results demonstrate the ability of ABM to predict
      heterogeneity and provide insights into the factors that contribute to it.
      Comparison of the ABM with an equivalent population-level model illustrates the
      effect of accounting for the heterogeneity in models.

PMID- 22360303
TI  - High-throughput generation of micropatterns of dye-containing capsules embedded
      in transparent elastomeric monoliths by inkjet printing.
AB  - We report the high-throughput fabrication of transparent elastomeric monoliths
      containing customized micropatterns of microcapsules, which might be used as
      highly flexible identity tags, sensor elements, and photochromic, photonic, or
      phononic systems. High-throughput replication molding of microsphere monolayers
      used as sacrificial primary templates via negative secondary replicas and
      positive tertiary replicas yielded elastomeric specimens containing dense
      hexagonal arrays of open spherical microcavities. In a subsequent inkjet printing
      step, some of the open-spherical microcavities were filled with functional
      materials such as dyes. The subsequent addition of an elastomeric cover layer led
      to encapsulation of the dyes trapped in the printed microcavities, while empty
      microcavities were filled with elastomer and vanished.

PMID- 22360304
TI  - Clarifying the mechanism of reverse structuring during electrodeposition in
      magnetic gradient fields.
AB  - Deviating from the common expectation, magnetoelectrochemical structuring during
      deposition of diamagnetic ions was demonstrated, very recently. To achieve this,
      electrochemically inert paramagnetic ions have to be added to the electrolyte and
      the deposition has to be performed in a magnetic gradient field. A reverse
      structuring occurs, yielding thinner deposits near high gradient regions. In this
      paper we aim to clarify the mechanism of this reverse structuring.
      Potentiodynamic and potentiostatic investigations were performed, including
      measurements of the deposited mass with an electrochemical quartz crystal
      microbalance (EQCM). The convection of the electrolyte was studied in situ by
      astigmatism particle tracking velocimetry (APTV). It was revealed that during the
      reverse structuring a convection is induced in the electrolyte, which is directed
      away from the working electrode in regions of high magnetic gradients. Due to
      this additional convection, the overall deposition rate is increased, whereby it
      is locally reduced in regions of high magnetic gradients. The mechanism for
      reverse structuring is discussed in detail. Also, the influence of all relevant
      magnetic forces is addressed.

PMID- 22360305
TI  - Aureocin A70 production is disseminated amongst genetically unrelated
      Staphylococcus aureus involved in bovine mastitis.
AB  - AIMS:   The main aim of this study was to analyse the genetic relationship
      amongst 46 Staphylococcus aureus Bac(+) strains isolated in Brazil from 12
      geographically distant dairy herds, including 34 isolates that produce the
      antimicrobial peptide aureocin A70. METHODS AND RESULTS:   The comparison of 46
      Staph. aureus Bac(+) strains was performed by pulsed-field gel electrophoresis
      (PFGE). Thirteen different pulsotypes were identified, and the subtype A(1) was
      the most prevalent one. Nine strains belong to pulsotype F, the second most
      prevalent and mostly confined to a single herd. The PFGE patterns of the 34
      Staph. aureus aureocin A70-producers, isolated in Brazil, were also compared with
      those of strains isolated from bovine mastitis cases in Argentina and revealed
      that these strains are not genetically related. CONCLUSIONS: Although a previous
      study has suggested that a prevalent pulsotype of aureocin A70-producer Staph.
      aureus involved in bovine mastitis is disseminated in Argentina, this does not
      occur in Brazil. Additionally, it was possible to demonstrate that closely
      related staphylococcal strains can produce distinct staphylococcins. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study corroborates the hypothesis of horizontal
      gene transfer of aureocin A70 genes amongst distinct staphylococcal strains
      involved in bovine mastitis, giving them a selective advantage when colonizing
      the mammary glands.

PMID- 22360307
TI  - Synthetic polymer nanoparticles conjugated with FimH(A) from E. coli pili to
      emulate the bacterial mode of epithelial internalization.
AB  - Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic 
      Escherichia coli  type 1 pilus adhesin FimH(A) through amidation chemistry to
      enable bladder epithelial cell binding and internalization of the nanoparticles
      in vitro.

PMID- 22360308
TI  - Intramolecular ipso-halocyclization of 4-(p-unsubstituted-aryl)-1-alkynes leading
      to spiro[4,5]trienones: scope, application, and mechanistic investigations.
AB  - A new, general method for the synthesis of spiro[4,5]trienones is described by
      the intramolecular ipso-halocyclization of 4-(p-unsubstituted-aryl)-1-alkynes. In
      the presence of halide electrophiles, a variety of 4-(p-unsubstituted-aryl)-1
      alkynes underwent the intramolecular ipso-halocyclization with water smoothly,
      affording the corresponding halo-substituted spiro[4,5]trienones in moderate to
      good yields. The obtained spiro[4,5]trienones can be applied in constructing the
      azaquaternary tricyclic skeleton via Pd-catalyzed Heck reaction. Notably, the
      prepared spiro[4,5]trienones and azaquaternary tricycles are of importance in the
      areas of pharmaceuticals and agrochemicals. The mechanism of the intramolecular
      ipso-halocyclization reaction is also discussed according to the (18)O-labeling
      experiments and DFT calculations.

PMID- 22360310
TI  - Health, lifestyle, belief and knowledge differences between two ethnic groups
      with specific reference to tobacco, diet and physical activity.
AB  - AIMS:   To compare physical activity levels, body mass index, habitual diet,
      tobacco use and prevalence of non-communicable disease between the two ethnic
      groups and to identify predictors for differences between groups. BACKGROUND:  
      Tobacco use, poor diet and physical inactivity are major lifestyle risk factors
      for chronic cardiovascular diseases, certain cancers, diabetes and chronic lung
      diseases. There are higher risk and incidence of these diseases in some ethnic
      groups, for example Asians have higher incidence of diabetes. DESIGN:   Cross
      sectional survey. METHODS:   Cross sectional survey of Asians of Indian descent
      and white British adults conducted between October-December 2009. Main outcome
      variables were lifestyle behaviours and BMI. Self-reported disease diagnosis was
      also collected. In a regression analysis, predictors of outcome variables were
      demographic variables and beliefs/attitudes/knowledge towards lifestyle
      behaviours. RESULTS/FINDINGS:   Body mass index, tobacco use and non-communicable
      disease (except diabetes) were lower in Indians. Indians reported lower physical
      activity levels and greater salt use than Whites. Tobacco use was higher in
      Whites, but knowledge, attitudes and beliefs were similar between Whites and
      Indians. CONCLUSION:   Health risk behaviour and morbidity are different between
      the two ethnic groups. Gender, age, educational level, beliefs, attitudes and
      knowledge do not explain these differences. Health promotion that aims to improve
      knowledge will probably not work and innovative methods are needed to improve
      health in high risk groups.

PMID- 22360309
TI  - Multivalent binding and facilitated diffusion account for the formation of the
      Grb2-Sos1 signaling complex in a cooperative manner.
AB  - Despite its key role in driving cellular growth and proliferation through
      receptor tyrosine kinase (RTK) signaling, the Grb2-Sos1 macromolecular
      interaction remains poorly understood in mechanistic terms. Herein, using an
      array of biophysical methods, we provide evidence that although the Grb2 adaptor
      can potentially bind to all four PXpsiPXR motifs (designated herein S1-S4)
      located within the Sos1 guanine nucleotide exchange factor, the formation of the
      Grb2-Sos1 signaling complex occurs with a 2:1 stoichiometry. Strikingly, such
      bivalent binding appears to be driven by the association of the Grb2 homodimer to
      only two of four potential PXpsiPXR motifs within Sos1 at any one time. Of
      particular interest is the observation that of a possible six pairwise
      combinations in which S1-S4 motifs may act in concert for the docking of the Grb2
      homodimer through bivalent binding, only S1 and S3, S1 and S4, S2 and S4, and S3
      and S4 do so, while pairwise combinations of sites S1 and S2 and sites S2 and S3
      appear to afford only monovalent binding. This salient observation implicates the
      role of local physical constraints in fine-tuning the conformational
      heterogeneity of the Grb2-Sos1 signaling complex. Importantly, the presence of
      multiple binding sites within Sos1 appears to provide a physical route for Grb2
      to hop in a flip-flop manner from one site to the next through facilitated
      diffusion, and such rapid exchange forms the basis of positive cooperativity
      driving the bivalent binding of Grb2 to Sos1 with high affinity. Collectively,
      our study sheds new light on the assembly of a key macromolecular signaling
      complex central to cellular machinery in health and disease.

PMID- 22360311
TI  - Tripartilactam, a cyclobutane-bearing tricyclic lactam from a Streptomyces sp. in
      a dung beetle's brood ball.
AB  - Tripartilactam, a structurally unprecedented cyclobutane-bearing tricyclic lactam
      metabolite, was discovered from Streptomyces sp. isolated from a brood ball of
      the dung beetle, Copris tripartitus. The structure of this compound was
      elucidated by the combination of NMR, MS, UV, and IR spectroscopy and multistep
      chemical derivatization. Tripartilactam was evaluated as a Na(+)/K(+) ATPase
      inhibitor (IC(50) = 16.6 MUg/mL).

PMID- 22360312
TI  - Effect of nitric oxide on the daunorubicin efflux mechanism in K562 cells.
AB  - NO (nitric oxide) donating drugs have been investigated for their important role
      in the sensitization of neoplastic cells to chemotherapy drugs. The goal of this
      work was to investigate the involvement of NO in the resistance of K562 cells to
      DNR (daunorubicin). Only simultaneous addition of DNR and SNAP (S-nitroso-N
      acetyl-dl-penicillamine) caused significant cell death by apoptosis. Combination
      of the compounds decreased Bcl-2 and survivin, and increased Bax and active
      caspase 3 expression. Fluorescence microscope and cytometric analysis showed that
      DNR and SNAP together caused DNR intracellular accumulation in K562 cells. RT-PCR
      (reverse transcription-PCR) analysis showed that DNR and SNAP, alone or in
      association, produced significant decreases in lrp expression. abcc1 gene
      expression was unaffected by the presence of SNAP, but when treated with DNR
      there was a small reduction that was intensified by DNR and SNAP in combination.
      The transport mechanism involved in the resistance to DNR in K562 cells involves
      ABCC1 and LRP (lung resistance protein) resistance proteins. DNR and SNAP
      inhibition of the expression of these proteins occurs by distinct mechanisms, and
      this disrupts the K562 resistance to DNR.

PMID- 22360315
TI  - Phenotyping of Staphylococcus aureus reveals a new virulent ST398 lineage.
AB  - Staphylococcus aureus sequence type (ST)398, which is commonly found as a
      colonization strain in pig farming, is emerging more frequently as the cause of
      human infections. In this study, we analysed ST398 of porcine and human origin at
      the genetic, protein and immunogenic levels. Although genetic analysis of the
      genes encoding the major virulence factors revealed the presence of the same
      genes in all strains studied, the results demonstrated spa type crossing
      alterations in adhesion abilities in addition to a strongly enhanced lysis
      activity directly linked to impaired clearance attributable to polymorphonuclear
      leukocytes (PMNs). This change in virulence pattern indicates high heterogenicity
      in the ST398 pool that is not based on a different genetic make-up, but probably
      on variations in the genetic regulation systems. These modifications, which are
      tightly connected to pathogenicity, cannot be detected by conventional diagnostic
      methods.

PMID- 22360313
TI  - Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with
      centrotemporal spikes.
AB  - PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS), the most common
      childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic
      influence. Despite its signature electroencephalographic pattern and distinct
      focal motor seizure semiology, little is known about the underlying brain
      anatomic alteration and the corresponding cognitive consequences. Given the motor
      manifestations of seizures in BECTS, we hypothesize that anatomic networks in
      BECTS involve a distributed corticostriatal circuit. METHODS: We investigated
      volumetric differences and shape deformities of caudate, putamen, pallidum, and
      thalamus in a group of children with new- and recent-onset BECTS (N =  3)
      compared to healthy controls (N = 54). We correlated specific subcortical volumes
      in BECTS that were significantly different from those in healthy controls with
      performances in executive function. KEY FINDINGS: Children with BECTS
      demonstrated significantly hypertrophied putamen, which was selective among the
      subcortical regions examined. Shape analysis showed dorsoventral elongation of
      the left caudate and bilateral putamen, with subnuclei expansion in ventral and
      dorsal striatum. Larger putamen volumes were linked to better cognitive
      performances on two complementary executive function tests. SIGNIFICANCE:
      Children with BECTS showed aberrant volume and shape in subcortical regions that
      are critical for both motor processing and executive function. It is of
      importance to note that the hypertrophy appears to be cognitively adaptive, as
      enlargement was associated with improved cognitive performances. The anatomic
      abnormalities and their cognitive effects are evident in a group of children with
      new- and recent-onset epilepsy, suggesting that the structural brain anomalies
      occurred before the diagnosis of epilepsy.

PMID- 22360314
TI  - Up-regulation of miR-210 by vascular endothelial growth factor in ex vivo
      expanded CD34+ cells enhances cell-mediated angiogenesis.
AB  - Ex vivo culture has been proposed as a means to augment and repair autologous
      cells in patients with chronic diseases, but the mechanisms governing improvement
      in cell function are not well understood. Although microRNAs (miRs) are
      increasingly appreciated as key regulators of cellular function, a role for these
      factors in CD34+ cell-mediated angiogenesis has not been elucidated. Vascular
      endothelial growth factor (VEGF) was previously shown to induce expression of
      certain miRs associated with angiogenesis in endothelial cells and promote
      survival and number of vascular colony forming units of haematopoietic stem cells
      (HSCs). We sought to evaluate the role of VEGF in expansion and angiogenic
      function of CD34+ cells and to identify specific miRs associated with angiogenic
      properties of expanded cells. Umbilical cord blood CD34+ cells were effectively
      expanded (18- to 22-fold) in culture medium containing stem cell factor (SCF),
      Flt-3 ligand (Flt-3), thrombopoietin (TPO) and interleukin-6 (IL-6) with
      (postEX/+VEGF) and without VEGF (postEX/noVEGF). Tube formation in matrigel assay
      and tissue perfusion/capillary density in mice ischaemic hindlimb were
      significantly improved by postEX/+VEGF cells compared with fresh CD34+ and
      postEX/noVEGF cells. MiR-210 expression was significantly up-regulated in
      postEX/+VEGF cells. MiR-210 inhibitor abrogated and 210 mimic recapitulated the
      pro-angiogenic effects by treatment of postEX/+VEGF and postEX/noVEGF cells
      respectively. Collectively, these observations highlight a critical role for VEGF
      in enhancing the angiogenic property of expanded cells, and identify miR-210 as a
      potential therapeutic target to enhance CD34+ stem cell function for the
      treatment of ischaemic vascular disease.

PMID- 22360316
TI  - Aerosol-based efficient delivery of clarithromycin, a macrolide antimicrobial
      agent, to lung epithelial lining fluid and alveolar macrophages for treatment of
      respiratory infections.
AB  - BACKGROUND: Macrolide antimicrobial agents are generally given by the oral route
      for the treatment of respiratory infections caused by pathogenic microorganisms
      infected in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs).
      However, because macrolides distribute to many different tissues via the blood
      after oral administration, systemic side effects are frequently induced. In
      contrast with oral administration, aerosolization may be an efficient method for
      delivering macrolides directly to ELF and AMs. In this study, the efficacy of
      aerosol-based delivery of clarithromycin (CAM), as a model macrolide, for the
      treatment of respiratory infections was evaluated by comparison with oral
      administration. METHOD: The aerosol formulation of CAM (0.2 mg/kg) was
      administered to rat lungs using a Liquid MicroSprayer((r)). The oral formulation
      of CAM (50 mg/kg) was used for comparison. Time courses of concentrations of CAM
      in ELF and AMs following administration were obtained, and then the
      bioavailability (BA) was calculated. In addition, the area under the
      concentrations of CAM in ELF and AMs-time curve/minimum inhibitory concentration
      at which 90% of isolates ratio [area under the curve (AUC/MIC(90))] were
      calculated to estimate the antibacterial effects in ELF and AMs. RESULTS: The BA
      of CAM in ELF and AMs following administration of aerosol formulation were
      markedly greater than that following administration of oral formulation. This
      indicates that the aerosol formulation is more effective in delivering CAM to ELF
      and AMs, compared with the oral formulation, despite a low dose. The AUC/MIC(90)
      of CAM in ELF and AMs were markedly higher than the effective values. This
      indicates that the aerosol formulation could be useful for the treatment of
      respiratory infections caused by pathogenic microorganisms infected in ELF and
      AMs. CONCLUSIONS: This study suggests that aerosol formulation of macrolides is
      an effective pulmonary drug delivery system for the treatment of respiratory
      infections.

PMID- 22360317
TI  - Delivery and safety of inhaled interferon-gamma in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Inhaled interferon-gamma aerosol (aINF-gamma) may be effective
      treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and
      delivery of aIFN-gamma (100 MUg 3 times/week) in 10 IPF patients using the I-neb
      (Philips Respironics, Parsippany, NJ). METHODS: IFN-gamma activity in the aerosol
      was confirmed by viral inhibition. Ten patients with an average age of 68
      diagnosed with IPF (American Thoracic Society/European Respiratory Society
      consensus guidelines) were enrolled. In vivo deposition was measured via a gamma
      camera. The nebulizer recorded patient adherence to therapy. Pulmonary function
      tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing
      capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at
      baseline, and every 12-14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the
      middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were
      analyzed for chemokines and cytokines, including INF-gamma. RESULTS: All 10
      patients tolerated 80 weeks of inhaled IFN-gamma well, with no systemic side
      effects. True adherence with aerosol treatment averaged 96.7 +/- 4.81% (+/- SEM).
      In vivo lung deposition averaged 65.4 +/- 4.8MUg and oropharyngeal deposition
      12.6 +/- 3.0 MUg. BAL IFN-gamma increased 60-fold and profibrotic cytokines (FGP
      2, Flt-3 ligand, IL-5) were significantly decreased; IFN-gamma plasma levels were
      unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that
      the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min
      walk was unchanged. CONCLUSIONS: IFN-gamma is safe in IPF and can be effectively
      delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal
      of pretherapy PFT decline may define an end-point for future clinical trials.

PMID- 22360318
TI  - New insights into hepatosplenic candidosis, a manifestation of chronic
      disseminated candidosis.
AB  - Chronic disseminated candidosis, often referred to as hepatosplenic candidosis
      (HSC), is an infection due to Candida spp. that mainly involves the liver and
      spleen. HSC occurs mostly in patients after profound and prolonged neutropenia,
      which is more often seen in patients with acute haematological malignancies. The
      incidence of HSC ranges from 3% to 29% in patients suffering from Acute
      Leukaemia. However, it is now seen less frequently with the widespread use of
      antifungal agents as prophylaxis or as preemptive therapy. Early and adequate
      diagnosis and treatment of HSC are crucial, as treatment delays can negatively
      affect the prognosis of the underlying condition. The pathogenesis is not well
      understood, but it is believed that it may be due to an unbalanced adaptive
      immune response that leads to an exacerbated inflammatory reaction, resulting in
      an Immune Reconstitution Inflammatory Syndrome. In this context, new therapeutic
      approaches such as the use of adjuvant high-dose corticosteroids have been shown
      beneficial. This article will focus on the clinical, diagnostic and therapeutic
      aspects of HSC and provide an accurate review of recent pathophysiological data.

PMID- 22360319
TI  - Adverse drug reactions.
AB  - Our ability to understand fully the characteristics of clinically important
      adverse drug reactions is hindered by a lack of emphasis on biological
      mechanisms, patient susceptibility factors and long-term outcomes. Assessment of
      drug safety needs to move beyond industry and regulatory perspectives, towards a
      greater focus on evidence-based preventive and management strategies that will
      allow patients and physicians to deal with adverse drug reactions at the bedside.
      This would ideally involve close collaboration between clinical pharmacologists
      and pharmacoepidemiologists skilled at interrogating the increasingly
      sophisticated electronic healthcare databases. In light of the myriad safety
      scares that are constantly emerging, patients and physicians would be best served
      by a centrally funded independent network of rapid-response drug safety
      researchers who can use techniques of teleoanalysis to describe fully the
      magnitude of risk, the potential biological mechanisms and patients'
      susceptibility factors.

PMID- 22360320
TI  - Obesity inequality in Malaysia: decomposing differences by gender and ethnicity
      using quantile regression.
AB  - OBJECTIVE: Obesity prevalence is unequally distributed across gender and ethnic
      group in Malaysia. In this paper, we examine the role of socioeconomic inequality
      in explaining these disparities. DESIGN: The body mass index (BMI) distributions
      of Malays and Chinese, the two largest ethnic groups in Malaysia, are estimated
      through the use of quantile regression. The differences in the BMI distributions
      are then decomposed into two parts: attributable to differences in socioeconomic
      endowments and attributable to differences in responses to endowments. RESULTS:
      For both males and females, the BMI distribution of Malays is shifted toward the
      right of the distribution of Chinese, i.e., Malays exhibit higher obesity rates.
      In the lower 75% of the distribution, differences in socioeconomic endowments
      explain none of this difference. At the 90th percentile, differences in
      socioeconomic endowments account for no more than 30% of the difference in BMI
      between ethnic groups. CONCLUSIONS: Our results demonstrate that the higher
      levels of income and education that accrue with economic development will likely
      not eliminate obesity inequality. This leads us to conclude that reduction of
      obesity inequality, as well the overall level of obesity, requires increased
      efforts to alter the lifestyle behaviors of Malaysians.

PMID- 22360321
TI  - Differentiation of subgroups of monosymptomatic enuresis according to prepulse
      inhibition of the startle reflex.
AB  - AIM: Monosymptomatic enuresis (ME) is a common disorder in children with serious
      social and psychological consequences. Treatment is usually initiated with
      desamino-arginine vasopressin (dDAVP) and/or alarm therapy as first-line
      treatment and imipramine as second-line. All treatments have proven efficacy, but
      are not successful with all patients. Therefore, a differentiation into subgroups
      according to treatment efficacy would be beneficial. METHODS: A group of patients
      resistant to first-line treatment was treated with imipramine and compared with
      matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse
      inhibition (PPI) to acoustic startle reflexes was measured in all patients.
      RESULTS: In a group of 23 nonresponders, the median PPI was 72% (range 43-94%)
      compared with the matched dDAVP/alarm - responders with a median PPI of 26%
      (range 0-61%) (p < 0.0001). The response rate to imipramine was 87%. CONCLUSION:
      The presented data provide evidence that PPI allows to identify two subgroups of
      ME. The results offer further insight into (at least) two different
      pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition
      with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns,
      that can be influenced by imipramine.

PMID- 22360322
TI  - New regulation mechanisms of osteoclast differentiation.
AB  - Osteoclasts play a crucial role in both physiological and pathological bone
      resorption. It is, thus, of compelling importance to understand the molecular
      mechanisms of osteoclast regulation. Because receptor activator of nuclear factor
      kappaB ligand (RANKL) is the key cytokine that induces osteoclast
      differentiation, we have focused on the investigation of RANKL signaling and
      RANKL-expressing cells. Here, we summarize the recent advances in the
      understanding of osteoclastogenic signaling and the cells that express RANKL in
      the context of osteoimmunology. The scope of osteoimmunology has been extended to
      now encompass a wide range of molecular and cellular interactions, and its
      framework provides a scientific basis for future therapeutic approaches to
      diseases related to the bone and/or immune systems.

PMID- 22360323
TI  - Molecular dynamics simulation of pyrene solubilized in a sodium dodecyl sulfate
      micelle.
AB  - In the present work, the structural and dynamical aspects of the solubilization
      process of pyrene within a sodium dodecyl sulfate micelle were studied using
      molecular dynamics simulations. Our results showed that free pyrene as the
      fluorescence probe can be spontaneously solubilized into the micelle and prefers
      to be located in the hydrophobic core region. As the local concentration of
      pyrene increased, two molecular probes could enter into the core hydrophobic
      region and the excited dimer of pyrene molecules was formed, showing a stacking
      mode of pi-pi conjugation. Since the pi-pi stacking interaction between the two
      pyrene molecules was very weak,  formation of the excimer was a dynamic process
      with the two pyrene molecules alternately separating and associating with each
      other. In this case, the two pyrene molecules were found to be mainly distributed
      in the palisade layer of the micelle due to the balance between the weak pi-pi
      stacking interaction and the hydrophobic interaction of probe molecules with the
      surfactant tails.

PMID- 22360326
TI  - Effect of continuous education for evidence-based medicine practice on knowledge,
      attitudes and skills of medical students.
AB  - OBJECTIVE: To assess the effect of the integration of evidence-based medicine
      (EBM) in a medical curriculum using small-group discussions with case scenario
      and problem-based learning on the knowledge, attitudes and skills of medical
      students. METHOD: A quasi-experimental study was conducted in a medical school in
      southern Thailand during 2008-2009. EBM practice was begun before the completion
      of the fourth year using case scenario and continued through the fifth year using
      learner-centred, problem-based self-practice. Knowledge improvement was measured
      by summative assessment using pre- and post-tests after small-group discussions
      with a case scenario. Attitudes and skills were measured by self-rating
      assessments: before initiation of the course (T0) and after the course at week 1,
      5, 13, 25 and 37 (T1, T2, T3, T4 and T5), respectively. Data were analyzed using
      paired t-test and linear mixed-effects model fitted by maximum likelihood.
      RESULTS: One hundred fourteen students took the course, with a mean age of 22.1
      years. Before and after knowledge scores showed a significant improvement (4.93
      versus 7.43). The proportion of students who achieved the highest knowledge
      scores was higher (4% at pre-test versus 54% at post-test). Both self-rated
      attitudes and skills after EBM practice increased dramatically from the
      initiation of the course (T0; P < 0.001). Compared with T1, significantly lower
      scores of attitudes and skills were observed at T2 and T3, but both were higher
      at T4 assessment. CONCLUSIONS: Continuous EBM education through small-group
      discussion and learner-centred, problem-based self-practice can be a useful way
      to improve a medical student's knowledge, attitudes and skills.

PMID- 22360327
TI  - The rise of cosmetic dermatology in the new medical model.

PMID- 22360328
TI  - Decrease in nicotinamide adenine dinucleotide dehydrogenase is related to skin
      pigmentation.
AB  - Skin pigmentation is caused by various physical and chemical factors. It might
      also be influenced by changes in the physiological function of skin with aging.
      Nicotinamide adenine dinucleotide (NADH) dehydrogenase is an enzyme related to
      the mitochondrial electron transport system and plays a key role in cellular
      energy production. It has been reported that the functional decrease in this
      system causes Parkinson's disease. Another study reports that the amount of NADH
      dehydrogenase in heart and skeletal muscle decreases with aging. A similar
      decrease in the skin would probably affect its physiological function. However,
      no reports have examined the age-related change in levels of NADH dehydrogenase
      in human skin. In this study, we investigated this change and its effect on skin
      pigmentation using cultured human epidermal keratinocytes. The mRNA expression of
      NDUFA1, NDUFB7, and NDUFS2, subunits of NADH dehydrogenase, and its activity were
      significantly decreased in late passage keratinocytes compared to early passage
      cells. Conversely, the mRNA expression of melanocyte-stimulating cytokines,
      interleukin-1 alpha and endothelin 1, was increased in late passage cells. On the
      other hand, the inhibition of NADH dehydrogenase upregulated the mRNA expression
      of melanocyte-stimulating cytokines. Moreover, the level of NDUFB7 mRNA was lower
      in pigmented than in nonpigmented regions of skin in vivo. These results suggest
      the decrease in NADH dehydrogenase with aging to be involved in skin
      pigmentation.

PMID- 22360329
TI  - Baseline sebum IL-1alpha is higher than expected in afro-textured hair: a risk
      factor for hair loss?
AB  - OBJECTIVE: To investigate changes in sebum cytokines in response to hair
      cosmetics. Design and setting  A prospective study at a University hospital.
      METHODS: We used a novel method for scalp surface sebum collection
      (Sebutape((r))) on three visits, sequentially a week apart, to investigate
      changes in six cytokines in 36 healthy women before and after shampoo and
      compared various chemical treatments (ammonium thioglycolate, "lye" sodium
      hydroxide and "no-lye" guanidine hydroxide relaxers) performed by a professional
      hairdresser. RESULTS:   Significant levels detected were IL-1 alpha (IL-1alpha)
      and IL-1 receptor antagonist (IL-1ra), which were higher in untreated scalp vs.
      forehead: P < 0.001. Baseline levels of scalp sebum IL-1alpha were 18 times
      higher than IL-1ra. The levels of IL-1alpha decreased uniformly after shampoo
      (visit 1) and various chemical treatments (both crown and vertex all P < 0.001 -
      visit 2) but increased on follow-up at visit 3. Decreases in IL-1ra mimicked IL
      1alpha at the vertex [after shampoo (P = 0.018) and visit 3 (P = 0.014)], but not
      on the crown, a finding which may suggest site-specific scalp predisposition to
      inflammation. The ratio of IL-1ra/IL-1alpha increased in all groups after all
      chemical treatments and on follow-up (all P < 0.001) but was surprisingly not
      significantly different from natural hair that underwent shampoo. LIMITATIONS:  
      A wider cytokine panel may reveal response differences in treatment groups.
      CONCLUSIONS:   Baseline inflammatory scalp cytokines are higher than expected and
      reduce with shampooing. Scrutiny of the influence of hair moisturizer
      formulations and shampoo intervals and studies investigating pro-fibrotic
      cytokines are required. This may elucidate the predilection of afro-textured hair
      to scarring alopecia.

PMID- 22360330
TI  - Effect of cosmetic ingredients as anticellulite agents: synergistic action of
      actives with in vitro and in vivo efficacy.
AB  - BACKGROUND: The pathophysiology of cellulite involves changes in the subcutaneous
      adipose layer and the extracellular matrix (ECM) that supports it together with
      overlying dermal layer. Cellular mechanisms governing cellulite are not fully
      understood. However, it is accepted that changes include enhanced lipogenesis,
      decreased lipolysis, and increased lipid storage within the adipocytes as well as
      changes in the dermal architecture. AIM: In our studies the ability of cosmetic
      agents Furcellaria lumbricalis, Fucus vesiculosus, retinoid, conjugated linoleic
      acid (CLA), and a glaucine mixture to stimulate in vitro 1) lipolysis in human
      adipocytes and 2) production of pro-collagen I by fibroblasts was investigated in
      vitro. The ability of these ingredients to improve cellulite condition in vivo
      was also determined. PATIENTS/METHODS: Mature adipocytes and 'aged' fibroblasts
      were used for in vitro studies. The assessment of cellulite in vivo was performed
      by dermatological grading and ultrasound measurements. RESULTS: Mature adipocytes
      treated with combined actives resulted in a significant synergistic increase in
      free glycerol release. On "aged" fibroblasts, combined treatment of F.
      vesiculosus and F. lumbricalis stimulated pro-collagen I production. CLA
      increased pro-collagen I production, but the glaucine mixture had no effect. The
      clinical study demonstrated a significant improvement in cellulite grading by a
      dermatologist after 8 and 12 weeks vs. vehicle, and ultrasound imaging showed a
      significant decrease in fat thickness compared with placebo after 12 weeks.
      CONCLUSIONS: Our studies revealed a potent cocktail of ingredients that when
      combined together can act in vitro to markedly improve lipolysis mechanisms and
      by way of stimulating pro-collagen I can also have an effect on the surrounding
      extracellular matrix. The in vitro actions of the ingredients were translated in
      vivo, where a clinical improvement of cellulite condition was observed.

PMID- 22360331
TI  - Nail damage from gel polish manicure.
AB  - Manicures can result in nail damage via instrumentation, nail polish, nail polish
      removers, and artificial nails. We report nail weakness, brittleness, and
      thinning in five subjects after the application of a new manicure system called
      gel polish and removal with acetone and manual peeling. All subjects complained
      that the polish was very difficult to remove and that their nails became much
      thinner after the procedure. Pseudoleukonychia and onychoschizia lamellina were
      noted on examination. One subject underwent ultrasound and reflectance confocal
      microscopy (RCM) measurements of nail plate before and after the gel polish
      application, which showed thinned nail plate (0.063 vs. 0.050 cm and 0.059 vs.
      0.030 cm, respectively). Overall, we call attention to the adverse effects of gel
      polish manicures in five subjects. In addition, our case illustrates potential
      utility of ultrasound and RCM in measuring nail plate thickness.

PMID- 22360332
TI  - Topically applied L-carnitine effectively reduces sebum secretion in human skin.
AB  - BACKGROUND:   Oily skin condition is caused by an excessive sebaceous gland
      activity, resulting in an overproduction of sebum, giving the skin an undesired
      shiny, oily appearance. AIMS:   To identify an active substance that reduces
      sebum production in human sebaceous glands by regulating fat metabolism in a
      natural way. PATIENTS/METHODS:   The effects of L-carnitine on beta-oxidation and
      intracellular lipid content were investigated in vitro using the human sebaceous
      cell line SZ95. Penetration experiments utilizing pig skin as a model system were
      performed with a cosmetic formulation containing radioactively labeled L
      carnitine. To determine the in vivo effects, a vehicle-controlled, randomized
      study was carried out using a cosmetic formulation containing 2%l-carnitine for 3
      weeks. Sebum production was investigated utilizing the lipid-absorbent
      Sebutape((r)). RESULTS:   SZ95 cells treated with 0.5% or 1% L-carnitine
      demonstrated a significant concentration-dependent increase in beta-oxidation
      compared to control cells. Following the treatment with L-carnitine,
      intracellular lipid concentrations decreased significantly in a dose-dependent
      manner compared with untreated control cells. In skin penetration experiments,
      topically applied L-carnitine reached the dermis. In addition, topical in vivo
      application of a formulation containing 2% L-carnitine for 3 weeks significantly
      decreased the sebum secretion rate compared to the treatment with vehicle.
      CONCLUSIONS:   Our results show that the treatment of human sebocytes with L
      carnitine significantly augments beta-oxidation and significantly decreases
      intracellular lipid content in human sebocytes. Topically applied L-carnitine is
      bioavailable and leads to a significant sebum reduction in vivo. In conclusion, L
      carnitine represents a valuable compound, produced naturally within the body, for
      the topical treatment of oily skin in humans.

PMID- 22360333
TI  - Clinical and instrumental assessment of the effects of a new product based on
      hydroxypropyl chitosan and potassium azeloyl diglycinate in the management of
      rosacea.
AB  - BACKGROUND:   Rosacea is a chronic inflammatory skin disease affecting mostly
      facial skin. Its origin is multifactorial. Important steps in its treatment are
      avoidance of any triggering factor and control of skin inflammation. AIM:   To
      assess the benefit of topical applications of a new product (P-3075).
      PATIENTS/METHODS:   A randomized, multicenter, double-blind, placebo-controlled,
      parallel-group, pilot study was carried out to evaluate the efficacy and
      tolerability of a cream (P-3075) based on 5% potassium azeloyl diglycinate (PAD,
      Azeloglicina((r))) and 1% hydroxypropyl chitosan (HPCH). Forty-two patients
      (rosacea stages I and II) were enrolled and randomized, 28 in the P-3075 group
      and 14 in the placebo group. They were asked to apply the cream twice daily for 4
      weeks. The main assessments were the objective quantification of erythema and
      skin hydration using the Mexameter((r)) and Corneometer((r)) devices,
      respectively. Clinical signs and symptoms were evaluated on a four-point scale.
      RESULTS:   The P-3075 cream applied for 28 days was effective in skin protection
      by reducing erythema, evaluated both instrumentally and clinically. In addition,
      the clinical assessments of other symptoms such as flushing, stinging, and
      burning supported the beneficial effect of the P-3075 cream. CONCLUSIONS:   The
      anti-inflammatory and moisturizing effects of potassium azeloyl diglycinate
      combined with the protective properties of HPCH allow the new product to be a
      good candidate for controlling signs and symptoms of rosacea.

PMID- 22360334
TI  - Advances in the use of botulinum neurotoxins in facial esthetics.
AB  - AIM:   To present the latest findings and future developments in the cosmetic use
      of botulinum neurotoxin. METHODS:   Review of recent literature and new
      scientific developments. RESULTS:   Botulinum neurotoxin type A preparations
      onabotulinumtoxinA (BOTOX((r)) Cosmetic/Vistabel((r)), Allergan Inc.) and
      abobotulinumtoxinA (Dysport((r)) /Azzalure((r)) /Reloxin((r)) , Ipsen Pharma,)
      have been used for many years and are effective and well tolerated for facial
      esthetic procedures. However, advances are continually made in the esthetics
      field. New formulations that may exhibit reduced antigenicity are becoming
      available, such as incobotulinumtoxinA (Xeomin((r)) /Xeomeen((r))
      /Bocouture((r)); formerly known as NT 201, Merz Pharma), which is a botulinum
      neurotoxin type A free from complexing proteins. In addition, lower facial
      procedures using botulinum toxin combined with fillers are becoming increasingly
      popular. Injection techniques and patterns are also evolving, with the aim of
      creating a more natural result and avoiding a "frozen" appearance. Moreover, the
      diversity of individuals requesting esthetic procedures is increasing, with
      growing interest from men and patients with a variety of skin types and colors.
      CONCLUSIONS:   The uses of botulinum toxins for facial esthetics procedures
      continue to expand, with new techniques and formulations. The availability of
      products such as incobotulinumtoxinA may reduce the risk of neutralizing antibody
      development while maintaining the good efficacy and safety of existing
      formulations.

PMID- 22360335
TI  - Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and
      cosmeceuticals.
AB  - The market for cosmeceuticals continues with significant annual growth, but today
      consumers are more aware of nutritional products that contribute to both skin
      health and disease prevention. In the last 10 years, pharmacists, chemists,
      nutritionists, and physicians have been working together to develop new
      nutritional applications to satisfy people's needs and demands. As a recent
      result of convergence phenomenon between cosmetics and food industries,
      nutricosmetics is a blurry area unfamiliar to many consumers and sometimes even
      to foods and cosmetics experts. Characterized by oral supplementation of
      nutrients, nutricosmetics are also known as "beauty pills,""beauty from within,"
      and even "oral cosmetics." The major claim is the antiaging effect, reducing
      wrinkles by fighting free radicals generated by solar radiation. Among the
      ingredients used in nutricosmetics, antioxidants represent the most crucial. The
      best-known antioxidants are carotenoids (beta-carotene, lycopene, lutein,
      zeaxanthin, and astaxanthin) and polyphenols (anthocyanidins, catechins,
      flavonoids, tannins, and procyanidins). This study presents an overview about the
      concept of nutricosmetics and gives us information about the difference between
      nutricosmetics, nutraceuticals, and cosmeceuticals. The article also discusses
      about carotenoids and polyphenols, two classes of ingredients often employed in
      such products.

PMID- 22360336
TI  - Cutaneous oxidative stress.
AB  - The earliest known microfossil records suggest that microorganisms existed on the
      earth approximately 3.8 billion years ago. Not only did sunlight drive this
      evolutionary process, but it also allowed photosynthetic organisms to elaborate
      oxygen and fundamentally change the earth's atmosphere and subsequent evolution.
      Paradoxically, however, an atmosphere of 20% oxygen offers aerobic organisms both
      benefits and some key challenges, particularly, to the external integument. This
      mini-review summarizes almost 40 years of research and provides a "60 000-foot"
      perspective on cutaneous oxidative stress. Topics reviewed include the following:
      What are free radicals and reactive oxygen species? Where do they come from? What
      is their chemistry? What are their roles and/or impact on the skin? What
      antioxidant defenses are available to mitigate oxidative stress.

PMID- 22360337
TI  - A single-blinded comparative study between the use of glycolic acid 70% peel and
      the use of topical nanosome vitamin C iontophoresis in the treatment of melasma.
AB  - BACKGROUND:   Melasma is a common pigmentary disorder. Despite the availability
      of a wide range of skin-lightening treatments, melasma of skin remains a
      therapeutic challenge. OBJECTIVE:   The aim of this study was to evaluate the
      efficacy and safety of nanosome vitamin C iontophoresis and to compare the
      therapeutic effects of nanosome vitamin C iontophoresis vs. glycolic acid peel
      70% in the treatment of melasma in Egyptian women. METHODS:   This study included
      14 patients of melasma with skin type IV-V taken for a right-left comparison
      study of six sessions. Glycolic acid 70% peel was applied on the right side,
      whereas nanosome vitamin C was applied by iontophoresis on the other side. The
      results are evaluated using the melasma area and severity index score and with
      photographs at baseline and after six sessions. Also the photographs were
      evaluated by two single-blinded physicians before and after sessions. RESULTS:  
      Both sides were improved, but the side treated with nanosome vitamin C showed
      better results. Side effects were few and transient. CONCLUSION:   We concluded
      that nanosome vitamin C is a new, safe and effective, easy and painless method in
      the treatment of melasma.

PMID- 22360338
TI  - In the shadow of the wrinkle: theories.
AB  - As time passes, wrinkles typically appear. These skin depressions that become
      deeper and deeper draw more and more coarser lines on almost all the visible
      parts of aging individual's skin. They are indeed the most obvious and maybe
      disliked signs of skin aging, and thus, preventing and treating them are a major
      topic for dermo-cosmetic laboratories. However, the cause and occurrence
      mechanism of these simplistic looking lines are not yet fully understood.
      Wrinkling is thought to be a complex biophysical process resulting from repeated
      strains on a progressively, structurally and biochemistry altered aging skin with
      impaired mechanical properties. Focus is made on the specific histological
      features of the wrinkle compared to the surrounding aging skin. The numerous age
      related changes in human skin that are supposed to be involved in wrinkling are
      briefly reviewed, and the current theories on wrinkle formation linked to these
      changes are also discussed.

PMID- 22360339
TI  - In the shadow of the wrinkle: experimental models.
AB  - Research on aging has run for decades, and knowledge on the biologic process of
      skin chronological and photoaging is still increasing thanks to read across
      results generated between human, animal, and in vitro studies. However, wrinkles
      should not be considered to result only from the aging process. There are few
      reports on specific wrinkle histological features compared to the surrounding
      skin, and there is thus a need in really wrinkling skin animal and in vitro
      models. UV-irradiated Hr mouse is a good model because it develops wrinkles.
      Nevertheless, as mouse skin is somehow different from human skin, the innovative
      model of wrinkling human skin xenograft on SCID mice seems to be really
      promising. Concerning in vitro and ex vivo models, although there have been
      considerable advances in reconstructing realistic aged skins, there is still a
      lack of in vitro wrinkling skin model, and unfortunately, this gap will probably
      be difficult to fill.

PMID- 22360340
TI  - Facile and rapid synthesis of highly porous wirelike TiO2 as anodes for lithium
      ion batteries.
AB  - Highly porous wirelike TiO(2) nanostructures have been synthesized by a simple
      two-step process. The morphological and structural characterizations reveal that
      the TiO(2) wires typically have diameters from 0.4 to 2 MUm, and lengths from 2
      to 20 MUm. The TiO(2) wires are highly porous and comprise of interconnected
      nanocrystals with diameters of 8 +/- 2 nm resulting in a high specific surface
      area of 252 m(2) g(-1). The effects of experimental parameters on the structure
      and morphology of the porous wirelike TiO(2) have been investigated and the
      possible formation processes of these porous nanostructures are discussed.
      Galvanostatic charge/discharge tests indicate that the porous wirelike TiO(2)
      samples exhibit stable reversible lithium ion storage capacities of 167.1 +/-
      0.7, 152.1 +/- 0.8, 139.7 +/- 0.3, and 116.1 +/- 1.1 mA h g(-1) at 0.5, 1, 2, and
      5 C rates, respectively. Such improved performance could be ascribed to their
      unique porous and 1D nanostructures facilitating better electrolyte penetration,
      higher diffusion rate of electrons and lithium ion, and variation of accommodated
      volumes during the charge/discharge cycles.

PMID- 22360342
TI  - NanoSIMS study of organic matter associated with soil aggregates: advantages,
      limitations, and combination with STXM.
AB  - Direct observations of processes occurring at the mineral-organic interface are
      increasingly seen as relevant for the cycling of both natural soil organic matter
      and organic contaminants in soils and sediments. Advanced analytical tools with
      the capability to visualize and characterize organic matter at the submicrometer
      scale, such as Nano Secondary Ion Mass Spectrometry (NanoSIMS) and Scanning
      Transmission X-ray Microscopy (STXM) coupled to Near Edge X-ray Absorption Fine
      Structure Spectroscopy (NEXAFS), may be combined to locate and characterize
      mineral-associated organic matter. Taking advantage of samples collected from a
      decadal (15)N litter labeling experiment in a temperate forest, we demonstrate
      the potential of NanoSIMS to image intact soil particles and to detect spots of
      isotopic enrichment even at low levels of (15)N application. We show how
      microsites of isotopic enrichment detected by NanoSIMS can be speciated by STXM
      NEXAFS performed on the same particle. Finally, by showing how (15)N enrichment
      at one microsite could be linked to the presence of microbial metabolites, we
      emphasize the potential of this combined imaging and spectroscopic approach to
      link microenvironment with geochemical process and/or location with ecological
      function.

PMID- 22360343
TI  - Adherence to a cardiac rehabilitation home program model of care: a comparison to
      a well-established traditional on-site supervised program.
AB  - Despite the proven benefits of cardiac rehabilitation (CR), adherence to programs
      remains suboptimal. To improve adherence, alternative models of care, such as
      using home programs (HP), have been recommended. Little information exists,
      however, about its effect on adherence in real-world settings. Therefore, this
      study's primary objective was to compare adherence of patients in an HP and
      traditional on-site program (TP) model of CR. The secondary objective was to
      compare their clinical and demographic profiles and changes in cardiovascular
      fitness. We implemented a retrospective review of 200 consecutively enrolled
      patients who chose either a TP or HP model. Profile data was collected at intake
      assessment. Adherence, defined as attendance to prescheduled contacts or on-site
      visits in each respective cohort, served as a primary outcome measure. Secondary
      outcomes included completion of program and cardiopulmonary fitness levels at 6
      months. We found that the HP cohort had patients who were significantly younger,
      male (significantly moreso than female), were more geographically removed from
      the on-site centre, were employed, and (or) had greater cardiopulmonary fitness
      at initiation. Similar mean attendance (p = 0.21) and completion rates (p = 0.22)
      were seen between models. Both groups attained similar gains in cardiovascular
      fitness (p = 0.79). Analysis of adherence shows the HP to be a suitable option
      for patients who face barriers for TP-CR participation.

PMID- 22360344
TI  - Energy expenditure and dietary intake during high-volume and low-volume training
      periods among male endurance athletes.
AB  - The primary purpose of this study was to examine dietary intake in endurance
      trained athletes during a week of high-volume and a week of low-volume training
      while measuring exercise energy expenditure (EEE), resting metabolic rate (RMR),
      and nonexercise activity thermogenesis (NEAT). In addition, compliance with
      current American College of Sports Medicine/American Dietetic Association
      nutrition and performance recommendations for macronutrients was evaluated.
      Energy expenditure and dietary intake were measured in 15 male endurance athletes
      during 2 nonconsecutive weeks resembling a high-volume and a low-volume training
      period. Anthropometric measurements were taken and percentage body fat was
      determined at the beginning and end of each week of training. Total daily energy
      expenditure (TDEE) was calculated by summing RMR, NEAT, and EEE. Dietary intake
      was assessed with an online food-frequency questionnaire completed at the end of
      each week of data collection. Despite significant differences between TDEE and
      energy intake, no difference in body composition between the beginning and end of
      either week of training was observed, suggesting underreporting of caloric
      intake. Further, no changes in total caloric intake or macronutrient intake
      occurred even though TDEE increased significantly during the high-volume
      training. Reported carbohydrate intake (4.5 g.kg(-1)) and fiber intake (25 g.day(
      1)) were below recommendations, whereas fat intake (1.3 g.kg(-1)) was slightly
      above recommendations. In summary, no short-term dietary adjustments occurred in
      response to differences in training regimen. Because these athletes were
      generally consuming a Western diet, they may have required some support to
      achieve desirable intakes for health and performance.

PMID- 22360345
TI  - Omega-3 improves glucose tolerance but increases lipid peroxidation and DNA
      damage in hepatocytes of fructose-fed rats.
AB  - The high consumption of fructose is linked to the increase in various
      characteristics of the metabolic syndrome. Fish oil is beneficial for the
      treatment of these comorbidities, such as insulin resistance, dyslipidemia, and
      hepatic steatosis. The objective of this study was to evaluate the consequences
      of the administration of fish oil concomitant to fructose ingestion during the
      experiment (45 days) and during the final 15 days in high-fructose-fed rats. Male
      Wistar rats were divided into 5 groups: control; those receiving 10% fish oil
      (FO); those receiving 60% fructose (Fr); those receiving 60% fructose and 10%
      fish oil for 45 days (FrFO); and those receiving fructose plus soybean oil for 30
      days and fish oil for the final 15 days of the study (FrFO15). There was an
      increase in triacylglycerol, serum total cholesterol, and hepatic volume in the
      Fr group. The FO and FrFO groups experienced an increase in lipid peroxidation
      and a decrease in serum reduced glutathione. The FrFO group suffered greater
      hepatic injury, with increased alanine aminotransferase levels and DNA damage.
      Marked n-3 incorporation occurred in the groups receiving fish oil, favoring a
      better response to the oral glucose tolerance test. Fructose induced
      comorbidities of the metabolic syndrome, and the use of fish oil promoted a
      better glucose tolerance, although it was accompanied by more hepatocyte damage.

PMID- 22360346
TI  - Theoretical and experimental investigations of circular dichroism and absolute
      configuration determination of chiral anthracene photodimers.
AB  - Substituted anthracenes photodimerize to stereoisomeric [4 + 4] cyclodimers, some
      of which are inherently chiral. Recent supramolecular photochirogenic studies
      enabled the efficient preparation of specific stereoisomers, the absolute
      configurations of which should reflect the chiral environment of supramolecular
      host or scaffold employed but have not been determined, hindering detailed
      mechanistic elucidation and further host/scaffold design. In this study, we
      performed the combined experimental and state-of-the-art theoretical analyses of
      the circular dichroism spectra of chiral cyclodimers of 2-anthracenecarboxylic
      and 2,6-anthracenedicarboxylic acids to reveal the configurational and molecular
      orbital origin of the Cotton effects observed, and unambiguously determined the
      absolute configurations of these chiral cyclodimers. The present results allow us
      to directly correlate the enantiotopic face-selectivity upon
      photocyclodimerization with the absolute configuration of the cyclodimer derived
      therefrom and also to precisely elucidate the chiral arrangement of two
      cyclodimerizing anthracenes.

PMID- 22360347
TI  - A novel PCR-based approach for the detection and classification of potential
      cellulolytic fungal strains isolated from museum items and surrounding indoor
      environment.
AB  - AIMS: To develop a novel PCR-based method able to detect potential cellulolytic
      filamentous fungi and to classify them exploiting the amplification of the
      cellobiohydrolase gene (cbh-I) and its polymorphism. METHODS AND RESULTS: A mixed
      approach including the combination of (i) fungal cultivation and isolation, (ii)
      classification of fungal isolates through the amplification of the cbh gene using
      a fluorescently labelled primer (f-CBH-PCR) and (iii) final fungal identification
      based on amplification and sequencing of the ITS1-5.8S rDNA-ITS2 region of the
      selected fungal strains was developed. By this approach, it was possible to
      screen 77 fungal strains belonging to 14 genera and 26 species. CONCLUSIONS: The
      f-CBH-PCR permitted the discrimination of fungal species, producing typical f-CBH
      profiles. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the cbh gene was
      used as a preliminary classification tool able to differentiate among themselves
      the fungal members isolated from indoor museum items and surrounding environment.
      Such mixed approach consented the fast identification of all isolated fungal
      strains. The f-CBH-PCR method demonstrated its discrimination power, and it can
      be considered as a new molecular system suitable for the classification of fungal
      strains isolated from different environments.

PMID- 22360348
TI  - The relationships of social support, uncertainty, self-efficacy, and commitment
      to prenatal psychosocial adaptation.
AB  - AIMS: To report a study of the relations of prenatal psychosocial adaptation,
      social support, demographic and obstetric characteristics, uncertainty,
      information-seeking behaviour, motherhood normalization, self-efficacy, and
      commitment to pregnancy. BACKGROUND: Prenatal psychosocial assessment is
      recommended to identify psychosocial risk factors early to prevent psychiatric
      morbidities of mothers and children. However, knowledge on psychosocial
      adaptation and its explanatory variables is inconclusive. DESIGN: This study was
      non-experimental, with a cross-sectional, correlational, prospective design.
      METHODS: The study investigated Hong Kong Chinese women during late pregnancy.
      Convenience sampling methods were used, with 550 women recruited from the low
      risk clinics of three public hospitals. Data was collected between January-April
      2007. A self-reported questionnaire was used, consisting of a number of
      measurements derived from an integrated framework of the Life Transition Theory
      and Theory of Uncertainty in Illness. Explanatory variables of psychosocial
      adaptation were identified using a structural equation modelling programme.
      RESULTS: The four explanatory variables of the psychosocial adaptation were
      social support, uncertainty, self-efficacy, and commitment to pregnancy. In the
      established model, which had good fit indices, greater psychosocial adaptation
      was associated with higher social support, higher self-efficacy, higher
      commitment to pregnancy, and lower uncertainty. CONCLUSION: The findings give
      clinicians and midwives guidance in the aspects to focus on when providing
      psychosocial assessment in routine prenatal screening. Since there are
      insufficient reliable screening tools to assist that assessment, midwives should
      receive adequate training, and effective screening instruments have to be
      identified. The explanatory role of uncertainty found in this study should
      encourage inquiries into the relationship between uncertainty and psychosocial
      adaptation in pregnancy.

PMID- 22360349
TI  - Evidence for modulatory sites at the lipid-protein interface of the human
      multidrug transporter P-glycoprotein.
AB  - The human multidrug transporter P-glycoprotein (Pgp or ABCB1) sets up
      pharmacological barriers to many clinically important drugs, a therapeutic remedy
      for which has yet to be formulated. For the rational design of mechanism-based
      inhibitors (or modulators), it is necessary to map the potential sites for
      modulator interaction and understand their modes of communication with the other
      functional domains of Pgp. In this study, combining directed mutagenesis with
      homology modeling, we provide evidence of two modulator-specific sites at the
      lipid protein interface of Pgp. Targeting 21 variant positions in the COOH
      terminal transmembrane (TM) regions, we find residues M948 (in TM11) and F983,
      M986, V988, and Q990 (all four in TM12) critically involved in substrate-site
      modulation by a thioxanthene-based allosteric modulator cis-(Z)-flupentixol.
      Interestingly, for ATP-site modulation by the same modulator, only two (M948 and
      Q990) of those four residues appear indispensable, together with two additional
      residues, T837 and I864 in TM9 and TM10, respectively, suggesting independent
      modes of communication linking the allosteric site with the substrate binding and
      ATPase domains. None of the seven residues identified prove to be critical for
      modulation of the substrate or ATP sites by Pgp modulators that are transported
      by the pump, such as cyclosporin A or verapamil, indicating their specificity for
      cis-(Z)-flupentixol. On the other hand, ATP-site modulation by verapamil proves
      to be highly sensitive to replacement at positions F716 (in TM7) and I765 (in
      TM8), and to a more moderate extent at I764 and L772 (both in TM8). Homology
      modeling based on the known crystal structures of the bacterial multidrug
      transporter SAV1866 and the mouse Pgp homologue maps the identified residues
      primarily at the lipid-protein interface of Pgp, in two spatially distinct
      modulator-specific clusters. The two modulatory sites demonstrate negative
      synergism in influencing ATP hydrolysis, consolidating their spatial
      distinctness. Because Pgp is known to recruit drug molecules directly from the
      lipid bilayer, identification of modulatory sites at the lipid-protein interface
      and at the same time outside the conventional central drug binding cavity is
      mechanistically revealing.

PMID- 22360350
TI  - Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and
      alkyl halides.
AB  - Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed
      reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with
      alkyl iodides or benzylic chlorides. A wide variety of functional groups are
      tolerated by this process, including common nitrogen protecting groups and C-B
      bonds. Even hindered ketones flanked by tertiary and secondary centers can be
      formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2)
      intermediate with the carboxylic acid derivative.

PMID- 22360352
TI  - Focal and generalized EEG paroxysms in childhood absence epilepsy: topographic
      associations and distinctive behaviors during the first cycle of non-REM sleep.
AB  - PURPOSE:   To better understand the nature of the focal spike-wave discharges
      (FSWDs) and focally led generalized spike-wave discharges (GSWDs) in typical
      childhood absence epilepsy (CAE) and by implication their nosologic and taxonomic
      significance. METHODS:   Twenty-four abnormal video-electroencephalography (EEG)
      studies from 13 consecutive children with CAE and good response to appropriate
      antiepileptic drugs (AEDs) were analyzed. We studied the association between the
      topography of absence onset and the ictal automatisms, and the topographic
      correlation between FSWDs and GSWDs and their respective behavior during
      hyperventilation and the different states of phasic and nonphasic non-rapid eye
      movement (NREM) sleep. GSWDs were considered as of "focal" onset if a lead-in
      could be visibly recognized at a paper speed of 60 mm/s, and were classified by
      their topography. KEY FINDINGS:   (1) Multifocal absences occurred in 10
      children; anterior onset was noted in 81 absences (73.6%) from 12 children and
      posterior in 18 (16.4%) from 7 children; there was no association between
      topography of absence onset and ictal automatisms; (2) FSWDs occurred in 85% of
      children and were multifocal in 73% of them; 85% of FSWDs were anterior and 14%
      posterior; (3) there was good topographic association between FSWDs and the
      leading spike of GSWDs of "focal" onset in all children with FSWDs; (4) both
      FSWDs and GSWDs increased during hyperventilation; (5) FSWDs occurred mainly
      during noncyclical NREM sleep and during periods of reduced vigilance of cyclical
      NREM sleep, whereas GSWDs occurred during the periods of enhanced vigilance of
      NREM sleep; GSWDs occurred significantly more frequently than FSWDs at the
      transition from reduced to enhanced vigilance of NREM sleep. SIGNIFICANCE:   Our
      findings suggest that in CAE focal EEG paroxysms reflect a system of multifocal
      nonlocalizing electrically unstable cortical areas that under the facilitatory
      influence of exogenous or endogenous factors like sleep instability can foster a
      corticothalamic response of sufficient strength to generate 3-Hz GSWDs that are
      conditionally sustainable and potentially ictal. FSWDs can be viewed as
      incomplete forms of the GSWDs; together they define the EEG identity of
      idiopathic "generalized" epileptogenesis.

PMID- 22360353
TI  - A bacterial-fungal metaproteomic analysis enlightens an intriguing multicomponent
      interaction in the rhizosphere of Lactuca sativa.
AB  - Fusarium oxysporum MSA 35 [wild-type (WT) strain] is an antagonistic isolate that
      protects plants against pathogenic Fusaria. This strain lives in association with
      ectosymbiotic bacteria. When cured of the prokaryotic symbionts [cured (CU)
      form], the fungus is pathogenic, causing wilt symptoms similar to those of F.
      oxysporum f.sp. lactucae. The aim of this study was to understand if and how the
      host plant Lactuca sativa contributes to the expression of the
      antagonistic/pathogenic behaviors of MSA 35 strains. A time-course comparative
      analysis of the proteomic profiles of WT and CU strains was performed. Fungal
      proteins expressed during the early stages of plant-fungus interaction were
      involved in stress defense, energy metabolism, and virulence and were equally
      induced in both strains. In the late phase of the interkingdom interaction, only
      CU strain continued the production of virulence- and energy-related proteins. The
      expression analysis of lettuce genes coding for proteins involved in resistance
      related processes corroborated proteomic data by showing that, at the beginning
      of the interaction, both fungi are perceived by the plant as pathogen. On the
      contrary, after 8 days, only the CU strain is able to induce plant gene
      expression. For the first time, it was demonstrated that an antagonistic F.
      oxysporum behaves initially as pathogen, showing an interesting similarity with
      other beneficial organisms such as mychorrizae.

PMID- 22360354
TI  - Recognition and sensing of biologically relevant anions in alcohol and mixed
      alcohol-aqueous solutions using charge neutral cleft-like glycol-derived pyridyl
      amidothiourea receptors.
AB  - In this paper, the synthesis and the spectroscopic investigation of new
      colorimetric receptors for anions 3-6, possessing a glycol chain at the 4
      position of the pyridyl ring, and 1 and 2, which lack such a chain, and the X-ray
      crystal structure of 2 is presented. Structures 3-6 are able to bind to anions in
      competitive media, such as alcohol or in a mixture of methanol and water, where
      the anion recognition gives rise to changes in the absorption spectra, which is
      red-shifted, in 1:1 or 1:2 (sensor/anion) stoichiometry. The anion recognition
      for 1 and 2 was also investigated in organic solvents and in a 4:1 mixture of
      DMSO/H(2)O. The binding of 1 to anions such as acetate, phosphate, and fluoride
      was also evaluated using (1)H NMR in DMSO-d(6).

PMID- 22360355
TI  - Medication errors.
AB  - Medication errors cause substantial harm to patients. We need good methods for
      counting errors, and we need to know how errors defined in different ways and
      ascertained by different methods are related to the harm that patients suffer. As
      errors arise within the complex and poorly designed systems of hospital and
      primary care, analysis of the factors that lead to error, for example by failure
      mode and effects analysis, may encourage better designs and reduce harms. There
      is almost no information on the best ways to train prescribers to be safe or to
      design effective computerized decision support to help them, although both are
      important in reducing medication errors and should be investigated. We also need
      to know how best to provide patients with the data they need to be part of
      initiatives for safer prescribing.

PMID- 22360356
TI  - Palladium nanoshell catalysts synthesis on highly ordered pyrolytic graphite for
      oxygen reduction reaction.
AB  - A novel approach for the synthesis of palladium (Pd) nanoshells on highly ordered
      pyrolytic graphite (HOPG) surfaces for the oxygen reduction reaction (ORR) is
      described. Magnetron sputtering deposition was used to synthesize Pd thin films
      and nanoshells of different thicknesses on HOPG surfaces. Electrospun polymer
      fibers mats of poly(ethylene) oxide (PEO) were used as templates for the Pd
      nanoshells formation. The palladium thicknesses between 25 and 95 nm were
      deposited by magnetron sputtering. Scanning electron microscopy and energy
      dispersive X-ray fluorescence spectroscopy were used to study the morphology and
      composition of the Pd nanoshells. Electrocatalytic activity toward the ORR and
      methanol tolerance in oxygen saturated 0.5 M H(2)SO(4) solution was determined.
      Palladium nanoshells presented higher electrocatalytic activity toward ORR than
      Pd thin films of similar electrodes thicknesses and geometric area. Since
      palladium has higher methanol tolerance than platinum, the Pd nanoshells are
      promising electrode materials for direct methanol fuel cells (DMFC).

PMID- 22360357
TI  - Vitamin D: an essential component for skeletal health.
AB  - Vitamin D deficiency is increasing worldwide. Ultraviolet rays are supposed to
      provide humans over 80% of our vitamin D requirement; the rest is received
      through diet and supplements. In addition to enhancing calcium absorption from
      the intestine and mineralization of the osteoid tissue, vitamin D has many other
      physiological effects, including neuromodulation, improving muscle strength and
      coordination, insulin release, immunity and prevention of infections, and
      curtailing cancer. Whether the increased incidence of vitamin D deficiency is
      related to increased incidences of nonskeletal disorders remains to be
      determined. Serum levels of 25-hydroxyvitamin [25(OH)D] above 30 ng/mL indicate
      vitamin D sufficiency. An additional 1,000 IU of vitamin D/day is sufficient for
      most lighter-skinned individuals, whereas an extra 2,000 IU/day is needed by the
      elderly and dark-skinned individuals to maintain normal 25(OH)D levels.
      Additional research is needed to clarify the relationship between vitamin D and
      the nonskeletal systems, nonclassic functions, and targets of vitamin D.

PMID- 22360358
TI  - Bloodstream infections as a marker of community-acquired sepsis severity. Results
      from the Portuguese community-acquired sepsis study (SACiUCI study).
AB  - The impact of bloodstream infection (BSI) on admission to hospital on the outcome
      of patients with community-acquired sepsis (CAS) admitted to intensive-care units
      (ICU) is largely unknown. We selected 803 adult patients consecutively admitted
      with CAS to one of 17 Portuguese ICU, in whom blood cultures were collected
      before initiation of antibiotic therapy during a 12-month period. A BSI was
      identified on hospital admission in 160 (19.9%) patients. Those with and without
      BSI had similar mean Simplified Acute Physiology Score (SAPS) II and age. The
      presence of BSI was independently associated with mortality in ICU (adjusted odds
      ratio 1.86; 95% confidence interval 1.20-2.89; p 0.005). On the 4th day in ICU,
      patients with BSI were found to be significantly more dependent on vasopressor
      support (p 0.002) but not on ventilatory support. Cumulative ICU mortality was
      significantly higher in BSI patients from the 9th day onwards. A seasonal
      variation of BSI isolates was noted: gram-negative BSI were more common in the
      summer, whereas in the winter, gram-positive infections were more frequent (p
      0.024), without mortality differences.

PMID- 22360359
TI  - Crystallization of new samarium polyborates.
AB  - Rare earth borates are important due to their excellent properties, especially
      for optics. Here, we report the hydrothermal synthesis and structural
      determination by single-crystal X-ray diffraction of two new samarium polyborates
      with layered structures, being constituted by hexaborate chains. These hexaborate
      chains are connected by samarium polyhedra, forming dense sheets that further
      interact with each other by hydrogen bonding via isolated boric acid between
      these sheets. The third phase possesses a three-dimensional framework structure.
      The thermal stability of selective samples has been studied. The crystallization
      of samarium borate depends highly on the experimental conditions. Three samarium
      polyborates have been crystallized in very similar experimental conditions,
      clearly indicating that new lanthanide borate compounds with tailored structures
      may be prepared in the future by careful choice of physicochemical conditions.

PMID- 22360360
TI  - Differential expression of Kv1.3 and Kv1.5 voltage-dependent K+ channels in human
      skeletal muscle sarcomas.
AB  - Because Kv1.3 and Kv1.5 K(+) channels are remodeled during tumorigenesis and
      participate in skeletal muscle proliferation, we analyzed their expression in
      human skeletal muscle sarcomas. Aggressive alveolar rhabdomyosarcoma (ARMS) and
      embryonal rhabdomyosarcoma (ERMS) were studied. Kv1.5 expression was moderate in
      adult muscle and low in ERMS, whereas it was notable in ARMS and embryonic
      samples. Kv1.3 expression showed no major differences between RMS and healthy
      samples. We found a correlation of Kv1.3 and Kv1.5 expression with the tumor
      malignancy.

PMID- 22360361
TI  - Peritoneal carcinomatosis: cytoreductive surgery and HIPEC--overview and basics.
AB  - Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous
      form of cancer that had been generally regarded as a sign of systemic tumor
      disease and as a terminal condition. The multimodal treatment approach for
      patients with peritoneal carcinomatosis, which had been conceived and developed,
      consists of what is known as cytoreductive surgery, followed by hyperthermic
      intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed
      intraoperatively and the histopathological differentiation, patients who undergo
      cytoreductive surgery and HIPEC have a significant survival benefit. Mean
      increases in the survival period ranging from six months to up to four years have
      now been reported. In view of the substantial logistic effort and the extent of
      the surgery involved, this treatment approach represents a major challenge both
      for patients and for surgical oncologists, as well as for the members of the
      overall interdisciplinary structure required, which includes oncology,
      anesthesiology and intensive care, psycho-oncology, and patient management. The
      surgical procedures alone may take 8-14 hr. The present paper provides an
      overview of the basis for the approach and the use of specialized classifications
      and quantitative prognostic indicators.

PMID- 22360362
TI  - Maintenance bevacizumab is associated with increased hemoglobin in patients with
      advanced, nonsquamous, non-small cell lung cancer.
AB  - We retrospectively analyzed hematologic parameters in 22 patients with advanced,
      nonsquamous, NSCLC undergoing VEGF inhibition on a phase II clinical trial of
      bevacizumab, carboplatin, and gemcitabine. We also examined TTP in relation to
      hemoglobin changes. Median hemoglobin increased significantly from a 12.9 g/dL
      pretreatment to 13.8 g/dL (p =.01) after the second cycle of maintenance
      bevacizumab until the first off cycle measurement. There was no difference in TTP
      in patients who achieved a rise in hemoglobin compared with patients who did not
      (median 238 days vs. 268 days, p =.38.) Maintenance bevacizumab is associated
      with increased hemoglobin in advanced, nonsquamous, NSCLC patients.

PMID- 22360364
TI  - Angiogenesis inhibition using an oncolytic herpes simplex virus expressing
      endostatin in a murine lung cancer model.
AB  - Herpes-mediated viral oncolysis alone is not sufficient to completely eradicate
      tumors. In this study we used a replication conditional, endostatin-expressing
      herpes simplex virus-1 mutant (HSV-Endo) in a murine lung cancer model. We
      hypothesized that the anti-angiogenic action of endostatin would improve upon the
      oncolytic effect of HSV-1. HSV-Endo was evaluated in a pulmonary metastases and
      orthotopic flank model, where there was significantly less tumor burden and
      reduced microvessel density compared to a control virus. Endostatin expression
      appears to improve the anti-tumor effect of HSV-1 in a lung cancer model.

PMID- 22360363
TI  - Permanent implantation of iodine-125 seeds as a salvage therapy for recurrent
      head and neck carcinoma after radiotherapy.
AB  - Seventeen patients with head and neck recurrent carcinoma underwent (125)I seed
      implantation under CT or ultrasound guidance. The actuarial D90 of the (125)I
      seeds implanted was 90-160 Gy (median, 126 Gy). Median follow-up was 10 months
      (range, 3-48 months). The median local control time was 16 months; the 1- and 2
      year local control rates were 66.5% and 49.9%, respectively. The 1- and 2-year
      survival rates were 51.3% and 38.5%, respectively (median, 16 months). None of
      the patients experienced grade 4 toxicity. (125)I seed implantation was a
      feasible and effective salvage treatment for patients with recurrent head and
      neck cancers.

PMID- 22360365
TI  - Microleakage of IPS empress 2 inlay restorations luted with self-adhesive resin
      cements.
AB  - OBJECTIVE: To assess the microleakage of three self-adhesive and one etch-and
      rinse resin cements when luting IPS Empress 2 (Ivoclar Vivadent, Liechtenstein)
      all-ceramic inlay restorations to the prepared cavities in extracted human
      molars. METHODS: The cylindrical Class V cavities were prepared on the buccal
      surfaces of 40 extracted human third molars using diamond burs. The IPS Empress 2
      ceramic inlays were placed with Multilink Sprint (Ivoclar Vivadent), RelyX Unicem
      (3M ESPE, USA), G-Cem (GC, Japan), or Variolink II (Ivoclar Vivadent) as the
      control group. After storage in distilled water at 37 degrees C for 24 hours,
      samples were subjected to 1000 thermal cycles between baths of 5 degrees C and 55
      degrees C, with a dwell time of 30 seconds. The microleakage scores were examined
      on the occlusal and gingival margins at 30* magnification after each sample was
      stained with 0.5% basic fuchsin and sectioned into three parts using a thin
      diamond blade (Isomet, Buehler, USA) (n=40). The extent of microleakage on both
      occlusal and gingival margins of the restorations was scored and recorded. The
      microleakage data were analyzed using Kruskall-Wallis and Mann-Whitney U-tests.
      RESULTS: Statistically significant differences were observed between the groups
      in both margins according to the Kruskall-Wallis and Mann-Whitney U-tests
      (p<0.05). Microleakage scores on the occlusal margins were Variolink II < RelyX
      Unicem < G-Cem = Multilink Sprint. Microleakage scores on the gingival margins
      are Variolink II = RelyX Unicem < G-Cem < Multilink Sprint. CONCLUSION: Self
      adhesive resin cements displayed higher microleakage scores on the occlusal
      margins, whereas on the gingival margins RelyX Unicem showed comparable
      microleakage results with the control samples.

PMID- 22360366
TI  - Shear bond strength of composite to deep dentin after treatment with two
      different collagen cross-linking agents at varying time intervals.
AB  - OBJECTIVE: This in vitro study evaluated the shear bond strength of composite
      resin to deep dentin using a total etch adhesive after treatment with two
      collagen cross-linking agents at varying time intervals. MATERIALS AND METHODS:
      Thirty freshly extracted human maxillary central incisors were sectioned
      longitudinally into equal mesial and distal halves (n=60). The proximal deep
      dentin was exposed, maintaining a remaining dentin thickness (RDT) of
      approximately 1 mm. The specimens were randomly divided into three groups based
      on the surface treatment of dentin prior to bonding as follows: group I (n=12,
      control): no prior dentin surface treatment; group II (n=24): dentin surface
      pretreated with 10% sodium ascorbate; and group III (n=24): dentin surface
      pretreated with 6.5% proanthocyanidin. Groups II and III were further subdivided
      into two subgroups of 12 specimens each, based on the pretreatment time of five
      minutes (subgroup A) and 10 minutes (subgroup B). Shear bond strength of the
      specimens was tested with a universal testing machine, and the data were
      statistically analyzed. RESULTS: Significantly higher shear bond strength to deep
      dentin was observed in teeth treated with 10% sodium ascorbate (group II) and
      6.5% proanthocyanidin (group III) compared to the control group (group I). Among
      the collagen cross-linkers used, specimens treated with proanthocyanidin showed
      significantly higher shear bond strength values than those treated with sodium
      ascorbate. No significant difference was observed between the five-minute and 10
      minute pretreatment times in groups II and III. CONCLUSION: It can be concluded
      that dentin surface pretreatment with both 10% sodium ascorbate and 6.5%
      proanthocyanidin resulted in significant improvement in bond strength of resin
      composite to deep dentin.

PMID- 22360368
TI  - Eye movements reveal no immediate "WOW" ("which one's weird") effect in autism
      spectrum disorder.
AB  - Autism spectrum disorder (ASD) and typically developed (TD) adult participants
      viewed pairs of scenes for a simple "spot the difference" (STD) and a complex
      "which one's weird" (WOW) task. There were no group differences in the STD task.
      In the WOW task, the ASD group took longer to respond manually and to begin
      fixating the target "weird" region. Additionally, as indexed by the first
      fixation duration into the target region, the ASD group failed to "pick up"
      immediately on what was "weird". The findings are discussed with reference to the
      complex information processing theory of ASD (Minshew & Goldstein,  1998 ).

PMID- 22360367
TI  - Adhesion of indirect MOD resin composite inlays luted with self-adhesive and self
      etching resin cements.
AB  - This study investigated the effect of loading on the bond strength to dentin and
      microleakage of MOD indirect composite restorations bonded with self-adhesive and
      self-etching resin cements with or without acid etching of the proximal enamel
      margins. Class II MOD cavities were prepared in 48 molar teeth into dentin and
      divided into three groups of 16 teeth. Impressions were taken and indirect
      composite inlays fabricated (Estenia C & B). The enamel margins of the proximal
      boxes of half the specimens were phosphoric acid etched, and the inlays were
      cemented with one of three cements (Panavia F 2.0, SA Cement, or Rely X Unicem).
      After luting, eight teeth in each cement group were mechanically loaded at 2.5
      cycles/s for 250,000 cycles. Unloaded teeth acted as controls. Teeth were stored
      in Rhodamine B solution for 24 hours, sectioned buccolingually at the proximal
      boxes to examine microleakage using confocal microscopy, and further sectioned
      for MUTBS testing of the resin-dentin interface. Analysis of variance was
      performed to assess the effect of loading and acid etching on microleakage and
      bond strength. Acid etching had no effect on microleakage. No significant
      difference in the dentin bond strengths between the three cements existed after
      loading. Panavia F 2.0 exhibited a significant reduction in bond strength. With
      regard to microleakage at the proximal boxes, loading had no effect on dye
      penetration at the cavity floor. However, at the axial walls, loading had a
      significant deleterious effect on Panavia F 2.0. No difference in microleakage
      existed between the three cements at both sites before and after loading. In
      conclusion, the two tested self-adhesive cements exhibited similar bond strengths
      before and after loading to the self-etching resin cement. Loading reduced dentin
      bond strengths and increased microleakage at the resin-dentin interface. However,
      acid etching of the enamel margins had no significant effect on microleakage in
      the approximal regions of the bonded inlays.

PMID- 22360369
TI  - X-ray absorption fine structure evidence for amorphous zinc sulfide as a major
      zinc species in suspended matter from the Seine River downstream of Paris, Ile-de
      France, France.
AB  - Zinc is one of the most widespread trace metals (TMs) in Earth surface
      environments and is the most concentrated TM in the downstream section of the
      Seine River (France) due to significant anthropogenic input from the Paris
      conurbation. In order to better identify the sources and cycling processes of Zn
      in this River basin, we investigated seasonal and spatial variations of Zn
      speciation in suspended particulate matter (SPM) in the oxic water column of the
      Seine River from upstream to downstream of Paris using synchrotron-based extend X
      ray absorption fine structure (EXAFS) spectroscopy at the Zn K-edge. First
      neighbor contributions to the EXAFS were analyzed in SPM samples, dried and
      stored under a dry nitrogen atmosphere or under an ambient oxygenated atmosphere.
      We found a sulfur first coordination environment around Zn (in the form of
      amorphous zinc sulfide) in the raw SPM samples stored under dry nitrogen vs an
      oxygen first coordination environment around Zn in the samples stored in an
      oxygenated atmosphere. These findings are supported by scanning electron
      microscopy and energy dispersive X-ray spectrometry observations. Linear
      combination fitting of the EXAFS data for SPM samples, using a large set of EXAFS
      spectra of Zn model compounds, indicates dramatic changes in the Zn speciation
      from upstream to downstream of Paris, with amorphous ZnS particles becoming
      dominant dowstream. In contrast, Zn species associated with calcite (either
      adsorbed or incorporated in the structure) are dominant upstream. Other Zn
      species representing about half of the Zn pool in the SPM consist of Zn-sorbed on
      iron oxyhydroxides (ferrihydrite and goethite) and, to a lesser extent, Zn-Al
      layered double hydroxides, Zn incorporated in dioctahedral layers of clay
      minerals and Zn sorbed to amorphous silica. Our results highlight the importance
      of preserving the oxidation state in TM speciation studies when sampling
      suspended matter, even in an oxic water column.

PMID- 22360371
TI  - Water-soluble nanodiamond.
AB  - Reduction of the graphenic edges of annealed nanodiamond by sodium in liquid
      ammonia leads to a nanodiamond salt that reacts with either alkyl or aryl halides
      by electron transfer to yield radical anions that dissociate spontaneously into
      free radicals and halide. The free radicals were observed to add readily to the
      aromatic rings of the annealed nanodiamond. Nanodiamonds functionalized by phenyl
      radicals were sulfonated in oleum, and the resulting sulfonic acid was converted
      to the sodium salt by treatment with sodium hydroxide. The solubility of the salt
      in water was determined to be 248 mg/L. Nanodiamond functionalized by carboxylic
      acid groups could be prepared by reacting 5-bromovaleric acid with the annealed
      nanodiamond salt. The solubility of the sodium carboxylate in water was found to
      be 160 mg/L.

PMID- 22360372
TI  - Control of the evolution of iron peroxide intermediate in superoxide reductase
      from Desulfoarculus baarsii. Involvement of lysine 48 in protonation.
AB  - Superoxide reductase is a nonheme iron metalloenzyme that detoxifies superoxide
      anion radicals O(2)(*-) in some microorganisms. Its catalytic mechanism was
      previously proposed to involve a single ferric iron (hydro)peroxo intermediate,
      which is protonated to form the reaction product H(2)O(2). Here, we show by pulse
      radiolysis that the mutation of the well-conserved lysine 48 into isoleucine in
      the SOR from  Desulfoarculus baarsii  dramatically affects its reaction with
      O(2)(*-). Although the first reaction intermediate and its decay are not affected
      by the mutation, H(2)O(2) is no longer the reaction product. In addition, in
      contrast to the wild-type SOR, the lysine mutant catalyzes a two-electron
      oxidation of an olefin into epoxide in the presence of H(2)O(2), suggesting the
      formation of iron-oxo intermediate species in this mutant. In agreement with the
      recent X-ray structures of the peroxide intermediates trapped in a SOR crystal,
      these data support the involvement of lysine 48 in the specific protonation of
      the proximal oxygen of the peroxide intermediate to generate H(2)O(2), thus
      avoiding formation of iron-oxo species, as is observed in cytochrome P450. In
      addition, we proposed that the first reaction intermediate observed by pulse
      radiolysis is a ferrous-iron superoxo species, in agreement with TD-DFT
      calculations of the absorption spectrum of this intermediate. A new reaction
      scheme for the catalytical mechanism of SOR with O(2)(*-) is presented in which
      ferrous iron-superoxo and ferric hydroperoxide species are reaction
      intermediates, and the lysine 48 plays a key role in the control of the evolution
      of iron peroxide intermediate to form H(2)O(2).

PMID- 22360370
TI  - Predictors of severe outcomes associated with Clostridium difficile infection in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: The increasing incidence of Clostridium difficile (C. difficile)
      infection (CDI) among patients with inflammatory bowel disease is well
      recognised. However, most studies have focused on demonstrating that CDI is
      associated with adverse outcomes in IBD patients. Few have attempted to identify
      predictors of severe outcomes associated with CDI among IBD patients. AIM: To
      identify clinical and laboratory factors that predict severe outcomes associated
      with CDI in IBD patients. METHODS: From a multi-institution EMR database, we
      identified all hospitalised patients with at least one diagnosis code for C.
      difficile from among those with a diagnosis of Crohn's disease or ulcerative
      colitis. Our primary outcome was time to total colectomy or death with follow-up
      censored at 180 days after CDI. Cox proportional hazards models were used to
      identify predictors of the primary outcome from among demographic, disease
      related, laboratory and medication variables. RESULTS: A total of 294 patients
      with CDI-IBD were included in our study. Of these, 58 patients (20%) met our
      primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate
      analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34-24.56), haemoglobin below 9
      g/dL (HR 5.29, 95% CI 1.58-17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI
      1.04-3.79) were independent predictors of our primary outcome. Examining
      laboratory parameters as continuous variables or shortening our primary outcome
      to include events within 90 days yielded similar results. CONCLUSION: Serum
      albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5
      mg/dL were independent predictors of severe outcomes in hospitalised IBD patients
      with Clostridium difficile infection.

PMID- 22360373
TI  - Nutrition and prevalence of undernutrition assessed by different diagnostic
      criteria in nursing homes for elderly people.
AB  - BACKGROUND: Undernutrition is the state produced by the intake of insufficient
      energy, macronutrients or micronutrients. The present study aimed to assess the
      prevalence of undernutrition using 10 different diagnostic criteria described in
      the literature and to assess its association with energy intake in an
      institutionalised elderly population. METHODS: The cross-sectional study included
      213 subjects, aged 65-96 years (135 women and 78 men), who lived in seven nursing
      homes in the province of Murcia, on the Mediterranean coast of Spain. Dietary
      intake and anthropometric and biochemical parameters were assessed, and 10
      different diagnostic criteria, taken from studies of elderly subjects similar to
      our population, were applied. RESULTS: The mean dietary intakes appeared to cover
      the recommended dietary intake for a Spanish elderly population. However, only
      58.2% of the studied subjects consumed 100% of the recommended dietary intake and
      15.5% of the subjects had an energy intake below 80% of the recommended dietary
      intake. Depending on the criteria used for the diagnosis, the proportion of
      patients with undernutrition varied between 2% and 57%. When the relationship
      between undernourishment, as defined by the different methods and intake
      deficiency, was assessed, a statistically significant relationship was only found
      for five of the 10 diagnostic criteria assessed. CONCLUSIONS:   Research needs to
      focus on the development and evaluation of specific nutritional assessment tools
      for application to older people aiming to improve the detection of those
      suffering (or who are at risk of suffering) undernutrition.

PMID- 22360375
TI  - Effective use of mass spectrometry for glycan and glycopeptide structural
      analysis.
AB  - Most proteins are glycosylated. Mass spectrometry methods are used for mapping
      glycoprotein glycosylation and detailed glycan structural determination. This
      technology enables precise characterization of recombinant glycoproteins in the
      pharmaceutical industry and academic biomedicine.

PMID- 22360376
TI  - Alternatives to the carcinogenicity bioassay for toxicity prediction: are we
      there yet?
AB  - INTRODUCTION: For decades, traditional toxicology has been the ultimate source of
      information on the carcinogenic potential of chemicals; however, with increasing
      demand on regulation of chemicals and decreasing resources for testing,
      opportunities to accept 'alternative' approaches have dramatically expanded. The
      need for tools able to identify carcinogens in shorter times and at a lower cost
      in terms of animal lives and money is still an open issue, and the present
      strategies and regulations for carcinogenicity prescreening do not adequately
      protect human health. AREAS COVERED: This paper briefly summarizes the theories
      on the early steps of carcinogenesis and presents alternative detection methods
      for carcinogens based on genetic toxicology, structure-activity relationships and
      cell transformation assays. EXPERT OPINION: There is evidence that the
      combination of Salmonella and structural alerts for the DNA-reactive carcinogens,
      and in vitro cell transformation assays for nongenotoxic carcinogens, permits the
      identification of a very large proportion of carcinogens. If implemented, this
      alternative strategy could improve considerably the protection of human health.

PMID- 22360378
TI  - Application of a computational model of vagus nerve stimulation.
AB  - OBJECTIVES: The most widely used and studied neurostimulation procedure for
      medically refractory epilepsy is vagus nerve stimulation (VNS) Therapy. The goal
      of this study was to develop a computational model for improved understanding of
      the anatomy and neurophysiology of the vagus nerve as it pertains to the
      principles of electrical stimulation, aiming to provide clinicians with a
      systematic and rational understanding of VNS Therapy. MATERIALS AND METHODS:
      Computational modeling allows the study of electrical stimulation of peripheral
      nerves. We used finite element electric field models of the vagus nerve with VNS
      Therapy electrodes to calculate the voltage field for several output currents and
      studied the effects of two programmable parameters (output current and pulse
      width) on optimal fiber activation. RESULTS: The mathematical models correlated
      well with strength-duration curves constructed from actual patient data. In
      addition, digital constructs of chronic versus acute implant models demonstrated
      that at a given pulse width and current combination, presence of a 110-MUm
      fibrotic tissue can decrease fiber activation by 50%. Based on our findings, a
      range of output current settings between 0.75 and 1.75 mA with pulse width
      settings of 250 or 500 MUs may result in optimal stimulation. CONCLUSIONS: The
      modeling illustrates how to achieve full or nearly full activation of the
      myelinated fibers of the vagus nerve through output current and pulse width
      settings. This knowledge will enable clinicians to apply these principles for
      optimal vagus nerve activation and proceed to adjust duty cycle and frequency to
      achieve effectiveness.

PMID- 22360377
TI  - Monitoring drug therapy.
AB  - Drug development has improved over recent decades, with refinements in analytical
      techniques, population pharmacokinetic-pharmacodynamic (PK-PD) modelling and
      simulation, and new biomarkers of efficacy and tolerability. Yet this progress
      has not yielded improvements in individualization of treatment and monitoring,
      owing to various obstacles: monitoring is complex and demanding, many monitoring
      procedures have been instituted without critical assessment of the underlying
      evidence and rationale, controlled clinical trials are sparse, monitoring
      procedures are poorly validated and both drug manufacturers and regulatory
      authorities take insufficient account of the importance of monitoring. Drug
      concentration and effect data should be increasingly collected, analyzed,
      aggregated and disseminated in forms suitable for prescribers, along with
      efficient monitoring tools and evidence-based recommendations regarding their
      best use. PK-PD observations should be collected for both novel and established
      critical drugs and applied to observational data, in order to establish whether
      monitoring would be suitable. Methods for aggregating PK-PD data in systematic
      reviews should be devised. Observational and intervention studies to evaluate
      monitoring procedures are needed. Miniaturized monitoring tests for delivery at
      the point of care should be developed and harnessed to closed-loop regulated drug
      delivery systems. Intelligent devices would enable unprecedented precision in the
      application of critical treatments, i.e. those with life-saving efficacy, narrow
      therapeutic margins and high interpatient variability. Pharmaceutical companies,
      regulatory agencies and academic clinical pharmacologists share the
      responsibility of leading such developments, in order to ensure that patients
      obtain the greatest benefit and suffer the least harm from their medicines.

PMID- 22360379
TI  - Using post-bronchodilator FEV1 is better than pre-bronchodilator FEV1 in
      evaluation of COPD severity.
AB  - BACKGROUND: The current standards for the diagnosis and treatment of patients
      with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) criteria based on post-bronchodilator spirometric values. However,
      clinical evidence for using the post-bronchodilator FEV1 in the severity
      classification has not been fully investigated. METHODS: Patients with COPD were
      enrolled and followed up prospectively between October 2006 and January 2011. We
      compared the observed 3-year risk of all causes and respiratory mortality with
      the risk predicted by the pre- and post-bronchodilator percent predicted FEV1.
      Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance
      status and severe AECOPD (acute exacerbation) were also compared between the two
      groups. The different severity classifications of COPD, measured according the
      GOLD guidelines by post- and pre-bronchodilator percent predicted FEV1 were
      compared for prediction of mortality. RESULTS: There were 35 deaths among the 300
      COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator
      percent predicted FEV1 was a significant independent predictor of mortality but
      pre-bronchodilator percent predicted FEV1 was not (p = 0.008 vs 0.126) and it was
      more strongly correlated with all studied predictors of outcome than the pre
      bronchodilator percent predicted FEV1. Kaplan-Meier analysis showed that the
      discrimination ability to predict mortality from the GOLD criteria using post
      bronchodilator percent predicted FEV1 (p = 0.009) was better than using pre
      bronchodilator percent predicted FEV1 (p = 0.131). CONCLUSIONS: The post
      bronchodilator percent predicted FEV1 is better than the pre-bronchodilator
      percent predicted FEV1 in the evaluation of the severity of disease in COPD
      patients and is more accurate in predicting the risk of death by the GOLD
      classification.

PMID- 22360380
TI  - Impact of COPD exacerbations on osteoporosis assessed by chest CT scan.
AB  - BACKGROUND: COPD pathology involves not only the lungs but also extrapulmonary
      abnormalities. Osteoporosis is one of the most important abnormalities because it
      may cause vertebral compression fractures and deteriorate pulmonary function.
      COPD patients have many risk factors for osteoporosis, such as low BMI, decreased
      activity, systemic inflammation, and use of corticosteroids. Some of these
      factors have been shown to deteriorate with COPD exacerbations. We previously
      demonstrated the correlation between emphysema and osteoporosis and between
      emphysema progression and COPD exacerbations. Thus, the hypothesis that
      exacerbation causes osteoporosis progression in COPD patients was investigated.
      METHODS: Forty-two COPD patients not on osteoporosis treatment for over 2 years
      were recruited. During follow-up, exacerbations had been prospectively recorded.
      Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and
      the annual change in BMD was calculated. The change was compared between patients
      with and without a history of exacerbations. RESULTS: The decrease in thoracic
      vertebral BMD was greater in patients with than in those without a history of
      exacerbations (median DeltaBMD mg/ml.year: -3.78 versus -0.30, p = 0.02).
      Moreover, multivariate regression analysis showed that exacerbations and baseline
      PaO2 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and
      R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking
      status, and airflow limitation. CONCLUSIONS: This is the first longitudinal study
      to demonstrate that COPD exacerbations are independently associated with
      osteoporosis progression. Osteoporosis progression should be evaluated in COPD
      patients, especially in those with a history of frequent exacerbations.

PMID- 22360381
TI  - Anemia is a mortality predictor in hospitalized patients for COPD exacerbation.
AB  - BACKGROUND: Anemia is a recognized prognostic factor in many chronic illnesses,
      but there is limited information about its impact on outcomes in patients
      hospitalized for acute COPD exacerbation (AECOPD). AIM: To investigate whether
      anemia exerts an effect on mortality in patients admitted for AECOPD after one
      year of follow-up. Methods. From November 2007 to November 2009 we recruited 117
      patients who required hospitalization due to an AECOPD. Clinical, functional and
      laboratory parameters on admission were prospectively assessed. Patients were
      followed up during one year. Mortality and days-to-death were collected. RESULTS:
      Mean age 72 (SD +/- 9); FEV1 37.4 (SD +/- 12); mortality after 1 year was 22.2%.
      Mean survival: 339 days. Comparing patients who died to those who survived we
      found significant differences (p < 0,000) in hemoglobin (Hb) (12.4 vs 13.8 mg/dl)
      and hematocrit (Ht) (38 vs 41%). Anemia (Hb < 13 g.dl-1) prevalence was 33%.
      Those who died had experienced 3.5 exacerbations in previous year vs 1.5
      exacerbations in the case of the survivors (p = 0.000). Lung function and
      nutritional status were similar, except for percentage of muscle mass (%) (35 vs
      39%; p = 0.015) and albumin (33 vs 37 mg/dl; p = 0.039). These variables were
      included in a Multivariate Cox Proportional Hazards Model; anemia and previous
      exacerbations resulted as independent factors for mortality. Mortality risk for
      patients with anemia was 5.9(CI: 1.9-19); for patients with > 1 exacerbation in
      the previous year was 5.9(CI: 1.3-26.5). CONCLUSION: Anemia and previous
      exacerbations were independent predictors of mortality after one year in patients
      hospitalized for AECOPD.

PMID- 22360382
TI  - Inaccuracy of estimating peak work rate from six-minute walk distance in patients
      with COPD.
AB  - INTRODUCTION: The cardiopulmonary exercise test (CPET) and the 6-minute walk test
      (6MWT) are used to prescribe the appropriate training load for cycling and
      walking exercise in patients with chronic obstructive pulmonary disease (COPD).
      The primary aims were: (i) to compare estimated peak work rate (Wpeak(estimated))
      derived from six existing Wpeak regression equations with actual peak work rate
      (Wpeak(actual)); and (ii) to derive a new Wpeak regression equation using six
      minute walk distance (6MWD) and conventional outcome measures in COPD patients.
      METHODS: In 2906 patients with COPD, existing Wpeak regression equations were
      used to estimate Wpeak using 6MWD and a new equation was derived after a stepwise
      multiple regression analysis. RESULTS: The 6 existing Wpeak regression equations
      were inaccurate to predict Wpeak(actual) in 82% of the COPD patients. The new
      Wpeak regression equation differed less between Wpeak(estimated) and
      Wpeak(actual) compared to existing models. Still, in 74% of COPD patients
      Wpeak(estimated) and Wpeak(actual) differed more than (+/-) 5 watts. CONCLUSION:
      In conclusion, estimating peak work load from 6MWD in COPD is inaccurate. We
      recommend assessment of Wpeak using CPET during pre-rehabilitation assessment in
      addition to 6MWT.

PMID- 22360384
TI  - Therapist adherence to interpersonal vs. supportive therapy for social anxiety
      disorder.
AB  - We assessed therapist adherence to interpersonal therapy (IPT) and supportive
      therapy (ST) in a controlled trial for social anxiety disorder. Raters blindly
      scored n = 133 videotapes from 53 participants using the Collaborative Study
      Psychotherapy Rating Scale (CSPRS). Results reveal statistical differences across
      groups, but higher than expected overlap. Greater use of IPT in beginning
      sessions predicted better outcome in both therapies. Suboptimal adherence may be
      due to the crossed design in which the same therapists delivered both IPT and ST.
      Since switching between different approaches is a clinical reality for
      integrative psychotherapists, these findings may have important clinical
      implications.

PMID- 22360383
TI  - Sildenafil for chronic obstructive pulmonary disease: a randomized crossover
      trial.
AB  - RATIONALE: Pulmonary hypertension with exercise is common in chronic obstructive
      pulmonary disease (COPD) and may contribute to exercise limitation in this
      disease. We aimed to determine the effects of treatment with sildenafil on
      exercise capacity in patients with COPD and emphysema. METHODS: We performed a
      randomized, double-blind, placebo-controlled 2-period crossover trial of
      sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without
      pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil
      (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or
      sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen
      consumption at peak exercise. RESULTS: Sildenafil had no effect on 6-minute walk
      distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2
      to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected
      difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p =
      0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02),
      worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse
      events were more frequent while receiving sildenafil (p = 0.005). CONCLUSIONS:
      Routine sildenafil administration did not have a beneficial effect on exercise
      capacity in patients with COPD and emphysema without pulmonary hypertension.
      Sildenafil significantly worsened gas exchange at rest and quality of life.
      (clinicaltrials.gov NCT00104637).

PMID- 22360385
TI  - Peroxynitrite mediates disruption of Ca2+ homeostasis by carbon monoxide via Ca2+
      ATPase degradation.
AB  - AIM: Sublethal carbon monoxide poisoning causes prolonged neurological damage
      involving oxidative stress. Given the central role of Ca(2+) homeostasis and its
      vulnerability to stress, we investigated whether CO disrupts neuronal Ca(2+)
      homeostasis. RESULTS: Cytosolic Ca(2+) transients evoked by muscarine in SH-SY5Y
      cells were prolonged by CO (applied via the donor CORM-2), and capacitative
      Ca(2+) entry (CCE) was dramatically enhanced. Ca(2+) store mobilization by
      cyclopiazonic acid was similarly augmented, as was the subsequent CCE, and that
      evoked by thapsigargin. Ca(2+) rises evoked by depolarization were also enhanced
      by CO, and Ca(2+) levels often did not recover in its presence. CO increased
      intracellular nitric oxide (NO) and all effects of CO were prevented by
      inhibiting NO formation. However, NO donors did not mimic the effects of CO. The
      antioxidant ascorbic acid inhibited effects of CO on Ca(2+) signaling, as did the
      peroxynitrite scavenger, FeTPPS, and CO increased peroxynitrite formation.
      Finally, CO caused significant loss of plasma membrane Ca(2+)ATPase (PMCA)
      protein, detected by Western blot, and this was also observed in brain tissue of
      rats exposed to CO in vivo. INNOVATION: The cellular basis of CO-induced
      neurotoxicity is currently unknown. Our findings provide the first data to
      suggest signaling pathways through which CO causes neurological damage, thereby
      opening up potential targets for therapeutic intervention. CONCLUSION: CO
      stimulates formation of NO and reactive oxygen species which, via peroxynitrite
      formation, inhibit Ca(2+) extrusion via PMCA, leading to disruption of Ca(2+)
      signaling. We propose this contributes to the neurological damage associated with
      CO toxicity.

PMID- 22360386
TI  - Human louse-transmitted infectious diseases.
AB  - Several of the infectious diseases associated with human lice are life
      threatening, including epidemic typhus, relapsing fever, and trench fever, which
      are caused by Rickettsia prowazekii, Borrelia recurrentis, and Bartonella
      quintana, respectively. Although these diseases have been known for several
      centuries, they remain a major public health concern in populations living in
      poor-hygiene conditions because of war, social disruption, severe poverty, or
      gaps in public health management. Poor-hygiene conditions favour a higher
      prevalence of body lice, which are the main vectors for these diseases. Trench
      fever has been reported in both developing and developed countries in populations
      living in poor conditions, such as homeless individuals. In contrast, outbreaks
      of epidemic typhus and epidemic relapsing fever have occurred in jails and
      refugee camps in developing countries. However, reports of a significantly high
      seroprevalence for epidemic typhus and epidemic relapsing fever in the homeless
      populations of developed countries suggest that these populations remain at high
      risk for outbreaks of these diseases. Additionally, experimental laboratory
      studies have demonstrated that the body louse can transmit other emerging or re
      emerging pathogens, such as Acinetobacter baumannii and Yersinia pestis.
      Therefore, a strict survey of louse-borne diseases and the implementation of
      efficient delousing strategies in these populations should be public health
      priorities.

PMID- 22360387
TI  - Investigation of rifampicin resistance mechanisms in Brucella abortus using MS
      driven comparative proteomics.
AB  - Mutations in the rpoB gene have already been shown to contribute to rifampicin
      resistance in many bacterial strains including Brucella species. Resistance
      against this antibiotic easily occurs and resistant strains have already been
      detected in human samples. We here present the first research project that
      combines proteomic, genomic, and microbiological analysis to investigate
      rifampicin resistance in an in vitro developed rifampicin resistant strain of
      Brucella abortus 2308. In silico analysis of the rpoB gene was performed and
      several antibiotics used in the therapy of Brucellosis were used for cross
      resistance testing. The proteomic profiles were examined and compared using MS
      driven comparative proteomics. The resistant strain contained an already
      described mutation in the rpoB gene, V154F. A correlation between rifampicin
      resistance and reduced susceptibility on trimethoprim/sulfamethoxazole was
      detected by E-test and supported by the proteomics results. Using 12 836 MS/MS
      spectra we identified 6753 peptides corresponding to 456 proteins. The resistant
      strain presented 39 differentially regulated proteins most of which are involved
      in various metabolic pathways. Results from our research suggest that rifampicin
      resistance in Brucella mostly involves mutations in the rpoB gene, excitation of
      several metabolic processes, and perhaps the use of the already existing
      secretion mechanisms at a more efficient level.

PMID- 22360388
TI  - Palladium-catalyzed regio- and stereoselective hydrosilylation of electron
      deficient alkynes.
AB  - Highly regio- and stereoselective hydrosilylation applicable to a broad range of
      electron-deficient alkynes has been established using palladium catalysis. The
      synthetic utility of the method has been demonstrated by further transformations
      of alpha-silylalkenes, particularly Hiyama coupling and stereoinverting
      iododesilylation followed by Suzuki-Miyaura coupling, which enables
      stereodivergent syntheses of alpha-arylenoates.

PMID- 22360390
TI  - Not behind the horizon anymore: interprofessional education and collaborative
      practice in Japan.

PMID- 22360391
TI  - "They come with multiple morbidities": a qualitative assessment of pharmacist
      prescribing.
AB  - This paper presents qualitative findings from a larger sequential mixed methods
      study which sought to provide an in-depth understanding of pharmacist prescribing
      from the perspective of pharmacist prescribers, medical colleagues and key
      stakeholders in Northern Ireland. Transcriptions were analyzed using thematic
      analysis as the interviews progressed and emergent themes were identified and
      coded (along with supporting quotes) independently and by consensus of the
      research team. Three major themes emerged in relation to pharmacist prescribing:
      the effect on patient care; challenges facing pharmacist prescribers and the
      importance of the interprofessional team (where two or more different professions
      with varied, yet complementary experience work together with a common purpose).
      Pharmacist prescribing may have the potential to reduce the medication burden for
      patients (as reported by pharmacists) as pharmacists tend to provide a more
      comprehensive medication review than doctors; the additional time for
      consultations made this possible. Further research is required on how
      interprofessional team working can be maximized in the context of pharmacist
      prescribing, particularly in relation to the management of multi-morbidity.

PMID- 22360389
TI  - Temporal requirements of heat shock factor-1 for longevity assurance.
AB  - Reducing the activity of the insulin/IGF-1 signaling pathway (IIS) modifies
      development, elevates stress resistance, protects from toxic protein aggregation
      (proteotoxicity), and extends lifespan (LS) of worms, flies, and mice. In the
      nematode Caenorhabditis elegans, LS extension by IIS reduction is entirely
      dependent upon the activity of the transcription factors DAF-16 and the heat
      shock factor-1 (HSF-1). While DAF-16 determines LS exclusively during early
      adulthood, it is required for proteotoxicity protection also during late
      adulthood. In contrast, HSF-1 protects from proteotoxicity during larval
      development. Despite the critical requirement for HSF-1 for LS extension, the
      temporal requirements for this transcription factor as a LS determinant are
      unknown. To establish the temporal requirements of HSF-1 for longevity assurance,
      we conditionally knocked down hsf-1 during larval development and adulthood of C.
      elegans and found that unlike daf-16, hsf-1 is foremost required for LS
      determination during early larval development, required for a lesser extent
      during early adulthood and has small effect on longevity also during late
      adulthood. Our findings indicate that early developmental events affect LS and
      suggest that HSF-1 sets during development of the conditions that enable DAF-16
      to promote longevity during reproductive adulthood. This study proposes a novel
      link between HSF-1 and the longevity functions of the IIS.

PMID- 22360392
TI  - Partnership working in services for children: use of the common assessment
      framework.
AB  - Transformation in the structure and delivery of services for children and young
      people in the UK Children Act (Department for Education & Skills, 2004. The
      Children Act. London: HMSO) initiated new alliances between statutory, public and
      voluntary agencies. Traditional relationships and notions of partnership have
      been extended, necessitating an innovative approach to dialogue and multiple
      perspectives. Hudson's assertion that although the "rhetoric on partnering
      remains strong, the real policy thrust is now about choice and contestability"
      (2006, Journal of Integrated Care, 14(1), 13-21) exemplifies the dynamic policy
      context around notions of partnership and the rationale for collaborative
      advantage. This paper explores the experiences of practitioners working in a
      relatively new multi-agency context--the common assessment framework (CAF).
      Envisaged as a standardized approach to the assessment of need and as a tool to
      facilitate integrated working, the CAF is utilized by practitioners in the UK to
      improve outcomes for children and young people. We present data from a study that
      employed an interpretative phenomenological analysis approach and gathered semi
      structured interviews with 20 practitioners. Interviews drew upon their
      experiences of interprofessional working in which diversity, partnership working,
      and competing aims and objectives emerged as significant themes. The insights
      that were gained are discussed in terms of their potential impact on service
      delivery in the UK and their contribution toward responsive practice across
      dynamic professional boundaries.

PMID- 22360398
TI  - Cross-linked hybrid nanofiltration membrane with antibiofouling properties and
      self-assembled layered morphology.
AB  - A new siloxane monomer, 3-(3-(diethoxy(2-(5-(4-(10-ethoxy-4-hydroxy-2,2-dimethyl
      11-oxa-2-ammonio-6-aza-10-silatridecan-10-yl)phenyl)-1,3,4-oxadi azol-2
      ylthio)ethyl)silyl)propylamino)-2-hydroxy-N,N,N-trimethylpropan-1-aminium
      chloride (OA), was synthesized by reported 3-((4-(5-(2-((3-aminopropyl)
      diethoxysilyl)ethylthio)-1,3,4-oxadiazol-2-yl)phenyl) diethoxysilyl)propan-1
      amine (APDSMO) and glycidyltrimethylammonium chloride (GDTMAC) by epoxide ring
      opening reaction. OA-poly(vinyl alcohol) (PVA) hybrid antibiofouling nanofilter
      (NF) membranes were prepared by acid-catalyzed sol-gel followed by formal cross
      linking. Membranes showed wormlike arrangement and self-assembled layered
      morphology with varying OA content. Hybrid NF membrane, especially OA-6, showed
      low surface roughness, high hydrophilic nature, low biofouling, high cross
      linking density, thermal and mechanical stablility, solvent- and chlorine
      tolerant nature, along with good permeability and salt rejection. Prepared OA-6
      hybrid NF membrane can be used efficiently for desalting and purification of
      water with about 2.0 g/L salt content (groundwater in major part of India). The
      described method provides novel route for producing antibiofouling membranes of
      diversified applications.

PMID- 22360397
TI  - Application of optical imaging and spectroscopy to radiation biology.
AB  - Optical imaging and spectroscopy is a diverse field that has been of critical
      importance in a wide range of areas in radiation research. It is capable of
      spanning a wide range of spatial and temporal scales, and has the sensitivity and
      specificity needed for molecular and functional imaging. This review will
      describe the basic principles of optical imaging and spectroscopy, highlighting a
      few relevant applications to radiation research.

PMID- 22360399
TI  - Current status of immunosuppressive agents for solid organ transplantation in
      children.
AB  - Immunosuppression after organ transplantation is complex and ever evolving. Over
      the past two decades, newer immunosuppressive agents have been introduced with an
      aim to provide better patient and graft survival. Improved therapeutic strategies
      have been developed offering the option to use combinations of drugs with non
      overlapping toxicities. There are, however, only a few clinical studies with
      robust data to rationalize the use of these agents in children. This review will
      discuss the newer immunosuppressive agents used for solid organ transplant, their
      current status in post-transplant management and prevention of allograft
      rejection.

PMID- 22360400
TI  - Successful resolution of inflammation and increased regulatory T cells in
      sirolimus-treated post-transplant allograft hepatitis.
AB  - This retrospective case series reviews our center's experience with sirolimus and
      a CNI as alternative therapy for the treatment of PTAH. It also characterizes
      regulatory T cells (Tregs) in PTAH. LT recipients with PTAH who had received or
      were receiving treatment with sirolimus were retrospectively identified (n = 12).
      Liver enzymes, immunohistochemistry, and histology were compared in all 12
      patients. Immunophenotyping for Tregs in peripheral blood mononuclear cells was
      performed on LT recipients with PTAH on conventional therapy with CNI,
      azathioprine +/- prednisone (CT) (n = 11), recipients with PTAH on sirolimus, CNI
      +/- prednisone (n = 8), recipients without PTAH (n = 25), and pre-transplant
      patients (n = 5). Severity of necro-inflammatory changes markedly improved with
      sirolimus. Treg frequency and number were significantly lower in recipients with
      PTAH on CT compared to (i) those on sirolimus (p = 0.002 and p = 0.01,
      respectively), and (ii) recipients without PTAH (p = 0.07 and p = 0.009,
      respectively). Treg frequency was significantly higher in recipients with PTAH on
      sirolimus compared to recipients without PTAH under CNI therapy (p = 0.027).
      Sirolimus in addition to a CNI is successful in reversing inflammation in LT
      recipients with PTAH. This is associated with significantly higher circulating
      Tregs.

PMID- 22360401
TI  - Changes in natural killer cell subsets in pediatric liver transplant recipients.
AB  - NK cells are important in the immune response against tumors and virally infected
      cells. A balance between inhibitory and activating receptors controls the
      effector functions of NK cells. We examined the fate of circulating NK cells and
      the expression of the NK cell-activating receptors in pediatric liver transplant
      recipients. Blood specimens were collected from 38 pediatric liver transplant
      recipients before transplant, and at one wk, one, three, six, and nine months,
      and one yr post-transplant. PBMCs were isolated and analyzed for the levels of NK
      cell activation receptors NKp30, NKp46, and NKG2D in the CD56(dim) CD16(+) and
      CD56(bright) CD16(+/-) subsets of NK cells. We demonstrated that there is a
      significant decrease in the percentage of circulating NK cells post-transplant
      (pretransplant 7.69 +/- 1.54 vs. one wk post-transplant 1.73 +/- 0.44) in
      pediatric liver transplant recipients. Interestingly, NKp30 expression is
      significantly increased, while NKp46 and NKG2D levels remain stable on the NK
      cells that persist at one wk post-transplant. These data indicate that the
      numbers and subsets of circulating NK cells are altered in children after liver
      transplantation.

PMID- 22360402
TI  - Pediatric en bloc kidney transplantation into pediatric recipients: the French
      experience.
AB  - Chronic shortage of available donor organs has led to re-evaluation of the use of
      en bloc kidney transplants. Although excellent results have been reported in
      adult patients, experience in pediatric patients remains limited because of
      potential early complications and poor long-term graft outcome. We report 14
      pediatric en bloc renal transplantations into 14 pediatric recipients, performed
      between 1990 and 2007 in France. We retrospectively analyzed demographic data,
      postoperative complications, and graft function with a median follow-up of five
      yr. Donor age ranged from four to 54 months. Complications were vascular graft
      thrombosis in four patients, leading to graft loss in two cases, and to excellent
      long-term graft function in the two others. Two hemorrhagic complications
      resulted in death in one case and in graft loss in the other. Six acute rejection
      episodes occurred in four patients. Median glomerular filtration rate at three
      months, one, five, and 10 yr was 90.8, 106, 87.8, and 66.1 mL/1.73 m(2) /min. We
      believe that en bloc transplantation may be an option for children with end-stage
      kidney disease.

PMID- 22360403
TI  - Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable
      pediatric liver transplant recipients.
AB  - Pharmacokinetic monitoring of CNI is unsatisfactory, because at comparable CNI
      blood concentrations frequency and severity of adverse effects vary considerably
      among individual patients. Determining the RGE of NFAT-regulated genes in
      leukocytes is a new pharmacodynamic approach to measure directly the functional
      consequences of calcineurin inhibition in T-lymphocytes. We compared clinical
      outcome parameters and RGE of activated T-cells after pLtx. We measured
      prospectively RGE of NFAT regulated genes in 33 pLTX recipients in the
      maintenance period after pLTX. CsA-treated patients with recurrent infections had
      significantly lower RGE rates (27%) than children without recurrent infections
      (50%; p = 0.04), whereas pharmacokinetic parameters of CsA and the concomitant
      immunosuppressive therapy were comparable between both groups. In patients on
      tacrolimus-based IS therapy NFAT RGE was only slightly reduced (90%).
      Pharmacodynamic monitoring of CsA by measurement of RGE in T-lymphocytes has the
      potential to identify over-immunosuppressed pediatric liver transplant recipients
      on a CsA-based IS therapy, while in children on low-dose tacrolimus therapy, RGE
      measurement does not provide additional clinically useful information.

PMID- 22360404
TI  - Pediatric liver transplantation for fibropolycystic liver disease.
AB  - Fibropolycystic liver disease includes CHF, Caroli's syndrome, and Caroli's
      disease. Patients with Caroli's disease and Caroli's syndrome have an increased
      risk of recurrent cholangitis, intrahepatic calculi, biliary cirrhosis, and
      cholangiocarcinoma. The aim of this study was to examine the post-transplantation
      outcomes of children with fibropolycystic liver disease. Of the 158 children
      transplanted at Seoul National University Hospital, there were four patients with
      Caroli's syndrome, two patients with CHF, and one patient with Caroli's disease.
      One patient underwent combined liver/kidney transplantation. Associated renal
      manifestations included ARPKD in three children and nephronophthisis in one
      child. The indications for LT were recurrent cholangitis, decompensated
      cirrhosis, and refractory complications of portal hypertension. Both graft and
      patient survival rates were 100% at a median follow-up period of two yr after LT.
      Three children with growth failure achieved catch-up growth after LT. In three
      patients with ARPKD, mean serum creatinine levels increased from 0.53 mg/dL at
      the time of LT to 0.91 mg/dL at the last follow-up (p = 0.01). LT is an excellent
      option for children with complications from fibropolycystic liver disease. Renal
      function should be monitored cautiously after LT in the patients with ARPKD.

PMID- 22360405
TI  - Gilbert's syndrome--a frequent cause of unconjugated hyperbilirubinemia in
      children after orthotopic liver transplantation.
AB  - Gilbert's syndrome is one major cause for unconjugated hyperbilirubinemia in
      healthy individuals with the prevalence being approximately 3.2-8.6%. It is
      caused by a mutation in the promoter region of the UGT1A1-gene with a prolonged
      TAA-repeat coding for the enzyme bilirubin UDP-glucuronosyltransferase (A(TA)(7)
      TAA allele). After OLT, Gilbert's disease of the transplanted liver can cause
      unconjugated hyperbilirubinemia. Therefore, we looked for the presence of
      A(TA)(7) TAA alleles in pediatric liver transplant recipients with unconjugated
      hyperbilirubinemia. Laboratory results of 106 pediatric liver transplant
      recipients (aged 0-17 yr) were evaluated for elevated total bilirubin over 2.0
      mg/dL (conjugated bilirubin <30%). In these patients, DNA of the liver graft was
      extracted from paraffin-embedded liver biopsy samples formerly taken for
      diagnostic reasons. The DNA was analyzed for A(TA)(7) TAA alleles in the promoter
      region of the UGT1A1-gene. In 4 of 106 pediatric liver transplant recipients we
      found unconjugated hyperbilirubinemia with total bilirubin above 2.0 mg/dL
      (conjugated bilirubin <30%). The analysis of the promoter region of the UGT1A1
      gene of the liver grafts showed three homozygous A(TA)(7) TAA alleles (homozygous
      Gilbert's syndrome) and one heterozygous A(TA)(7) TAA allele (heterozygous
      Gilbert's syndrome). This study shows that pediatric liver transplant recipients
      with unconjugated hyperbilirubinemia are very likely to have received a liver
      graft from a donor with Gilbert's syndrome.

PMID- 22360406
TI  - Geochemical and strontium isotope characterization of produced waters from
      Marcellus Shale natural gas extraction.
AB  - Extraction of natural gas by hydraulic fracturing of the Middle Devonian
      Marcellus Shale, a major gas-bearing unit in the Appalachian Basin, results in
      significant quantities of produced water containing high total dissolved solids
      (TDS). We carried out a strontium (Sr) isotope investigation to determine the
      utility of Sr isotopes in identifying and quantifying the interaction of
      Marcellus Formation produced waters with other waters in the Appalachian Basin in
      the event of an accidental release, and to provide information about the source
      of the dissolved solids. Strontium isotopic ratios of Marcellus produced waters
      collected over a geographic range of ~375 km from southwestern to northeastern
      Pennsylvania define a relatively narrow set of values (epsilon(Sr)(SW) = +13.8 to
      +41.6, where epsilon(Sr) (SW) is the deviation of the (87)Sr/(86)Sr ratio from
      that of seawater in parts per 10(4)); this isotopic range falls above that of
      Middle Devonian seawater, and is distinct from most western Pennsylvania acid
      mine drainage and Upper Devonian Venango Group oil and gas brines. The uniformity
      of the isotope ratios suggests a basin-wide source of dissolved solids with a
      component that is more radiogenic than seawater. Mixing models indicate that Sr
      isotope ratios can be used to sensitively differentiate between Marcellus
      Formation produced water and other potential sources of TDS into ground or
      surface waters.

PMID- 22360407
TI  - Electronic spectra and excited states of neptunyl and its [NpO2Cl4]2- complex.
AB  - Electronic states and spectra of NpO(2)(2+) and NpO(2)Cl(4)(2-) with a Np 5f(1)
      ground-state configuration, related to low-lying 5f-5f and ligand-to-metal charge
      transfer (CT) transitions, are investigated, using restricted-active-space
      perturbation theory (RASPT2) with spin-orbit coupling. Restrictions on the
      antibonding orbital occupations have little influence on the 5f-5f transition
      energies, but an important impact on the CT states with an open bonding orbital
      shell. The present calculations provide significant improvement over previous
      literature results. The assignment of the experimental electronic spectra of
      Cs(2)NpO(2)Cl(4) is refined, based on our calculations of NpO(2)Cl(4)(2-).
      Assignments on the basis of bare NpO(2)(2+) are less reliable, since the
      equatorial Cl ligands perturb the excited-state energies considerably. Calculated
      changes of the Np-O bond lengths are in agreement with the observed short
      symmetric-stretching progressions in the f-f spectra and longer progressions in
      the CT spectra of neptunyl. A possible luminescence spectrum of the lowest
      quartet CT state is predicted.

PMID- 22360408
TI  - [Abstracts of the German Society of Dermatology Compact. February 24-25, 2012.
      Berlin, Germany].

PMID- 22360410
TI  - Foaming and foam stability for mixed polymer-surfactant solutions: effects of
      surfactant type and polymer charge.
AB  - Solutions of surfactant-polymer mixtures often exhibit different foaming
      properties, compared to the solutions of the individual components, due to the
      strong tendency for formation of polymer-surfactant complexes in the bulk and on
      the surface of the mixed solutions. A generally shared view in the literature is
      that electrostatic interactions govern the formation of these complexes, for
      example between anionic surfactants and cationic polymers. In this study we
      combine foam tests with model experiments to evaluate and explain the effect of
      several polymer-surfactant mixtures on the foaminess and foam stability of the
      respective solutions. Anionic, cationic, and nonionic surfactants (SDS, C(12)TAB,
      and C(12)EO(23)) were studied to clarify the role of surfactant charge. Highly
      hydrophilic cationic and nonionic polymers (polyvinylamine and
      polyvinylformamide, respectivey) were chosen to eliminate the (more trivial)
      effect of direct hydrophobic interactions between the surfactant tails and the
      hydrophobic regions on the polymer chains. Our experiments showed clearly that
      the presence of opposite charges is not a necessary condition for boosting the
      foaminess and foam stability in the surfactant-polymer mixtures studied. Clear
      foam boosting (synergistic) effects were observed in the mixtures of cationic
      surfactant and cationic polymer, cationic surfactant and nonionic polymer, and
      anionic surfactant and nonionic polymer. The mixtures of anionic surfactant and
      cationic polymer showed improved foam stability, however, the foaminess was
      strongly reduced, as compared to the surfactant solutions without polymer. No
      significant synergistic or antagonistic effects were observed for the mixture of
      nonionic surfactant (with low critical micelle concentration) and nonionic
      polymer. The results from the model experiments allowed us to explain the
      observed trends by the different adsorption dynamics and complex formation
      pattern in the systems studied.

PMID- 22360412
TI  - Systematic review: faecal transplantation for the treatment of Clostridium
      difficile-associated disease.
AB  - BACKGROUND: Management of recurrent Clostridium difficile-associated disease
      (CDAD), particularly in elderly patients, remains clinically challenging. Faecal
      transplantation (FT) may restore normal microbiota and break the cycle of
      recurrent CDAD. AIM: To critically appraise the clinical research evidence on the
      safety and effectiveness of FT compared with standard care in the treatment of
      patients with CDAD. METHODS: A comprehensive literature search was conducted by a
      research librarian to identify relevant studies published between 2000 and 2011.
      The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS
      Previews and Web of Science were searched using the following Medical Subject
      Headings (MeSH) terms and keywords, alone or in combination: Clostridium
      infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon
      flora/gastrointestinal/nasogastric
      tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion.
      Methodological quality of the included case series studies was assessed in terms
      of patient selection criteria, consecutive recruitment, prospective data
      collection, reporting of lost to follow-up, and follow-up rates. RESULTS: No
      controlled studies were found. Based on the weak evidence from seven full-text
      case series studies of 124 patients with recurrent/refractory CDAD, FT appears to
      be a safe and effective procedure. In most cases (83%) symptoms improved
      immediately after the first FT procedure, and some patients stayed diarrhoea free
      for several months or years. CONCLUSIONS: Although these results appear to be
      promising, the treatment effects of faecal transplantation cannot be determined
      definitively in the absence of a control group. Results from randomised
      controlled trials that compare faecal transplantation to oral vancomycin without
      or with a taper regimen will help to better define the role of faecal
      transplantation in the management of recurrent CDAD.

PMID- 22360411
TI  - Coronary artery wall imaging in mice using osmium tetroxide and micro-computed
      tomography (micro-CT).
AB  - The high spatial resolution of micro-computed tomography (micro-CT) is ideal for
      3D imaging of coronary arteries in intact mouse heart specimens. Previously,
      micro-CT of mouse heart specimens utilized intravascular contrast agents that
      hardened within the vessel lumen and allowed a vascular cast to be made. However,
      for mouse coronary artery disease models, it is highly desirable to image
      coronary artery walls and highlight plaques. For this purpose, we describe an ex
      vivo contrast-enhanced micro-CT imaging technique based on tissue staining with
      osmium tetroxide (OsO(4) ) solution. As a tissue-staining contrast agent, OsO(4)
      is retained in the vessel wall and surrounding tissue during the fixation process
      and cleared from the vessel lumens. Its high X-ray attenuation makes the artery
      wall visible in CT. Additionally, since OsO(4) preferentially binds to lipids, it
      highlights lipid deposition in the artery wall. We performed micro-CT of heart
      specimens of 5- to 25-week-old C57BL/6 wild-type mice and 5- to 13-week-old
      apolipoprotein E knockout (apoE(-/-) ) mice at 10 MUm resolution. The results
      show that walls of coronary arteries as small as 45 MUm in diameter are visible
      using a table-top micro-CT scanner. Similar image clarity was achieved with
      1/2000th the scan time using a synchrotron CT scanner. In 13-week-old apoE mice,
      lipid-rich plaques are visible in the aorta. Our study shows that the combination
      of OsO(4) and micro-CT permits the visualization of the coronary artery wall in
      intact mouse hearts.

PMID- 22360413
TI  - Rh(I)-catalyzed asymmetric synthesis of 3-substituted isoindolinones through CO
      gas-free aminocarbonylation.
AB  - A highly efficient and accessible synthesis of chiral 3-substituted isoindolinone
      frameworks is described. The synthesis involved the Rh(I)-catalyzed asymmetric
      arylation of boronic acids to 2-halobenzaldimines and the subsequent Rh(I)
      catalyzed intramolecular aminocarbonylation of the resulting 2-halobenzylamines
      using an aldehyde as the carbonyl source. The method tolerates a variety of
      functional groups, yielding isoindolinone derivatives in moderate to high yields
      with high ee-values. In addition, two Rh(I)-catalyzed transformations could be
      efficiently accomplished in a one-pot sequence to give chiral isoindolinones by
      the simple addition of a ligand and an aldehyde after the Rh(I)-catalyzed
      asymmetric arylation.

PMID- 22360414
TI  - Trans-alpha-xylosidase and trans-beta-galactosidase activities, widespread in
      plants, modify and stabilize xyloglucan structures.
AB  - Cell-wall components are hydrolysed by numerous plant glycosidase and glycanase
      activities. We investigated whether plant enzymes also modify xyloglucan
      structures by transglycosidase activities. Diverse angiosperm extracts exhibited
      transglycosidase activities that progressively transferred single sugar residues
      between xyloglucan heptasaccharide (XXXG or its reduced form, XXXGol) molecules,
      at 16 MUM and above, creating octa- to decasaccharides plus smaller products. We
      measured remarkably high transglycosylation:hydrolysis ratios under optimized
      conditions. To identify the transferred monosaccharide(s), we devised a dual
      labelling strategy in which a neutral radiolabelled oligosaccharide (donor
      substrate) reacted with an amino-labelled non-radioactive oligosaccharide
      (acceptor substrate), generating radioactive cationic products. For example, 37
      MUM [Xyl-3H]XXXG plus 1 mM XXLG-NH2 generated 3H-labelled cations, demonstrating
      xylosyl transfer, which exceeded xylosyl hydrolysis 1.6- to 7.3-fold, implying
      the presence of enzymes that favour transglycosylation. The transferred xylose
      residues remained alpha-linked but were relatively resistant to hydrolysis by
      plant enzymes. Driselase digestion of the products released a trisaccharide
      (alpha-[3H]xylosyl-isoprimeverose), indicating that a new xyloglucan repeat unit
      had been formed. In similar assays, [Gal-3H]XXLG and [Gal-3H]XLLG (but not [Fuc
      3H]XXFG) yielded radioactive cations. Thus plants exhibit trans-alpha-xylosidase
      and trans-beta-galactosidase (but not trans-alpha-fucosidase) activities that
      graft sugar residues from one xyloglucan oligosaccharide to another.
      Reconstructing xyloglucan oligosaccharides in this way may alter oligosaccharin
      activities or increase their longevity in vivo. Trans-alpha-xylosidase activity
      also transferred xylose residues from xyloglucan oligosaccharides to long-chain
      hemicelluloses (xyloglucan, water-soluble cellulose acetate, mixed-linkage beta
      glucan, glucomannan and arabinoxylan). With xyloglucan as acceptor substrate,
      such an activity potentially affects the polysaccharide's suitability as a
      substrate for xyloglucan endotransglucosylase action and thereby modulates cell
      expansion. We conclude that certain proteins annotated as glycosidases can
      function as transglycosidases.

PMID- 22360415
TI  - Cost analysis of metallic ureteral stents with 12 months of follow-up.
AB  - BACKGROUND AND PURPOSE: The metallic ureteral stent was first developed for
      patients with ureteral obstruction related to malignant disease, but it can be
      used in all patients needing chronic indwelling ureteral stents, including those
      with benign disease. The traditional method of polymer stent management often
      necessitates multiple exchanges per year depending on patient and logistical
      factors. This has significant direct financial cost and likely a negative effect
      on patients' overall health. The objective was to analyze and compare the costs
      associated with chronic indwelling metal and silicone-based ureteral stents.
      PATIENTS AND METHODS: A prospective database of patients undergoing metal stent
      placement from February 2008 to June 2010 was reviewed. Mean charges for a single
      traditional nonmetal and metal stent insertion were calculated. Charges were
      based on direct hospital charges related to stent cost and surgery. Cost data
      were based on the fiscal year 2010 cost for polymer or metal stent insertions.
      RESULTS: Twenty-one patients underwent metal stent placement at our institution.
      Of these, three traditional stent placements were omitted from analysis because
      of bundled charges for ureteroscopy at the same setting. Mean charges per single
      traditional and metal stent placement were $6072.75 and $9469.50, respectively.
      The estimated annual charges for traditional stents (3-6 exchanges) would be
      $18,218.25 to $36,436.50. Compared with metal stents, this is a potential
      financial savings of 48% to 74%. The mean direct cost to patients was 21.6% and
      25.4% of the charges for metal and polymer stents, respectively. No patient
      needed early discontinuation of his or her metal stent because of lower urinary
      tract symptoms or gross hematuria. CONCLUSIONS: Metal stents are well tolerated
      by patients with ureteral obstruction of various etiologies and provide a
      significant financial benefit compared with polymer ureteral stents. For patients
      who are not fit for surgical intervention regarding their ureteral occlusive
      disease, the metal Resonance stent is a financially advantageous and well
      tolerated option.

PMID- 22360416
TI  - Knowledge and attitudes of Polish university students toward organ donation and
      transplantation.
AB  - Although the number of patients needing organ transplantation systematically
      increases, recent years have seen a considerable shortage of donors. The level of
      knowledge and attitudes toward donation are critical factors in achieving the
      required balance between supply and demand. This pilot study assessed the
      knowledge, opinions, and behaviors related to organ donation and transplantation
      among 625 students representing eight different fields of study from the
      University of Rzeszow in south-eastern Poland. Although the participants provided
      evidence of knowledge about human organ donation and transplantation, they were
      aware of the main organs of the human body for potential transplants, and
      generally showed positive attitudes; only 24% of the subjects indicated their
      willingness to register as a donor; only 3% stated that they had already
      registered and had a donor card. The findings suggest that good intentions do not
      translate into action and that Poland needs to develop a nation-wide, up-to-date,
      and youth-oriented health education program that builds on favorable attitudes
      toward organ donation and transplantation.

PMID- 22360418
TI  - Research priorities in pharmacokinetics.
AB  - An opinion is expressed on the past, present and future roles of pharmacokinetic
      pharmacodynamic research in the context of UK clinical pharmacology. On the basis
      of its current constitution, it seems unlikely that this area of research will be
      driven from within academic clinical pharmacology in the UK. Therefore, in order
      to bring its expertise and experience to bear effectively on the evolving
      emphasis on translational medicine and modelling and simulation, this community
      would need to reach out beyond its current preoccupations to increase
      interactions with the next generation of pharmacokineticists and
      pharmacometricians.

PMID- 22360417
TI  - Examination of glycan profiles from IgG-depleted human immunoglobulins
      facilitated by microscale affinity chromatography.
AB  - Among the most important proteins involved in disease and healing processes are
      the immunoglobulins (Igs). Although many of the Igs have been studied through
      proteomics, aside from IgG, immunoglobulin carbohydrates have not been
      extensively characterized in different states of health. It seems valuable to
      develop techniques that permit an understanding of changes in the structures and
      abundances of Ig glycans in the context of disease onset and progression. We have
      devised a strategy for characterization of the glycans for the Ig classes other
      than IgG (i.e., A, D, E, and M) that contain kappa light chains that requires
      only a few microliters of biological material. First, we designed a microcolumn
      containing recombinant Protein L that was immobilized on macroporous silica
      particles. A similarly designed Protein G microcolumn was utilized to first
      perform an online depletion of the IgG from the sample, human blood serum, and
      thereby facilitate enrichment of the other Igs. Even though only 3 MUL of serum
      was used in these analyses, we were able to recover a significantly enriched
      fraction of non-IgG immunoglobulins. The enrichment properties of the Protein L
      column were characterized using a highly sensitive label-free quantitative
      proteomics LC-MS/MS approach, and the glycomic profiles of enriched
      immunoglobulins were measured by MALDI-TOF MS. As a proof of principle, a
      comparative study was conducted using blood serum from a small group of lung
      cancer patients and a group of age-matched cancer-free individuals to demonstrate
      that the method is suitable for investigation of glycosylation changes in
      disease. The results were in agreement with a glycomic investigation of whole
      blood serum from a much larger lung cancer cohort.

PMID- 22360419
TI  - Refractory pemphigoid gestationis postpartum.

PMID- 22360420
TI  - Proteomic analysis identifies dysfunction in cellular transport, energy, and
      protein metabolism in different brain regions of atypical frontotemporal lobar
      degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) is an umbrella term for a heterogeneous
      group of young-onset dementias of uncertain prevalence and incidence worldwide.
      Atypical cases of FTLD with fused in sarcoma inclusions (aFTLD-U) have been
      described recently, but their molecular characterization is still due. Using
      shotgun mass spectrometry, we identified a total of 107 differentially expressed
      proteins in the prefrontal cortex, cerebellum and occipital lobe from aFTLD-U
      patients compared to controls. These proteins are involved in a range of
      biological pathways such as cellular transport in the prefrontal cortex, energy
      metabolism in the cerebellum, and protein metabolism in the occipital lobe. In
      addition, they were validated by selective reaction monitoring (SRM). Comparison
      of the aFTLD-U proteomic findings with similar studies of Alzheimer's disease and
      schizophrenia led to identification of proteins that may be related to dementias
      and psychoses, respectively. Further studies of aFTLD-U and other FTLD subtypes
      are warranted, although this will require intensive biobanking efforts.

PMID- 22360421
TI  - Therapist directives: use and outcomes in China.
AB  - We examined relationships among the use of therapist directives, client
      implementation of directives, and outcome for 43 Chinese therapists and their 96
      Chinese clients at a university counseling center in mid-China. The results
      showed that most directives reported by both therapists and clients asked clients
      to act on or think about intrapersonal or interpersonal issues. Chinese
      therapists reported giving fewer, but clients reported receiving a similar number
      of directives than was found in Scheel et al.'s (1999) American sample. Client
      rated fit, difficulty, and therapist influence did not predict client
      implementation directly, nor did implementation predict client-rated outcome
      directly. Instead, quantity and acceptability of directives interacted in
      influencing client implementation and use of directives facilitated client-rated
      outcome through strengthening working alliance.

PMID- 22360422
TI  - Parity in patients with chronic inflammatory arthritides childless at time of
      diagnosis.
AB  - OBJECTIVE: To assess parity in women with chronic inflammatory arthritides (CIA)
      childless at time of diagnosis. METHODS: Patients were selected from the
      Norwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) registry. Each
      patient was matched by year of birth with 100 reference women from the Norwegian
      Population Registry. Data linkage for patients and references with the Medical
      Birth Registry of Norway (MBRN) identified all offspring until time of linkage
      (October 2007). Patients and corresponding references childless at the time of
      diagnosis were included in the analyses. Kaplan-Meier curves visualized the
      proportion of childless women and were compared by a log rank test. RESULTS: In
      all, 156 rheumatoid arthritis (RA), 107 other chronic arthritides (OCA), and 75
      juvenile idiopathic arthritis (JIA) patients were childless at time of diagnosis.
      At the time of data linkage, the proportions (%) of childless RA/OCA/JIA patients
      versus references were 61.5/62.6/57.3 versus 46.9/42.9/41.0, respectively, all
      differences statistically significant. The log rank test showed lower parity in
      all diagnostic groups compared with references (p < 0.001 for RA and OCA and p =
      0.002 for JIA). No difference in parity was observed between RA and OCA patients,
      but both diagnostic groups had lower parity than JIA patients (p = 0.001).
      Disease characteristics were similar between childless and fertile patients.
      CONCLUSIONS: Reduced parity was observed in all diagnostic groups compared with
      references. RA and OCA patients had lower parity than JIA patients, indicating
      that having the disease as a young adult may influence parity more than having
      the disease in childhood.

PMID- 22360423
TI  - Evaluation of the detection of Mycobacterium tuberculosis with metabolic activity
      in culture-negative human clinical samples.
AB  - Mycobacterium tuberculosis is assumed to remain in a quiescent state during
      latent infection, being unable to grow in culture. The aim of this study was to
      evaluate the detection of viable but non-cultivable bacilli with metabolic
      activity in human clinical samples using a procedure that is independent of the
      immunological status of the patient. The study was performed on 66 human clinical
      samples, from patients subjected to routine diagnosis to rule out a mycobacterial
      infection. Specimens from pulmonary and extra-pulmonary origins were verified to
      contain human DNA before testing for M. tuberculosis DNA, rRNA and transient RNA
      by real-time quantitative PCR. Clinical records of 55 patients were also
      reviewed. We were able to detect viable but non-cultivable bacilli with a
      metabolic activity in both pulmonary and extra-pulmonary samples. Mycobacterium
      tuberculosis RNA was detected in the majority of culture-positive samples whereas
      it was detected in one-third of culture-negative samples, 20% of them showed
      metabolic activity. Amplifications of the ftsZ gene and particularly of the main
      promoter of the ribosomal operon rrnA, namely PCL1, seem to be good targets to
      detect active bacilli putatively involved in latent infection. Moreover, this
      last target would provide information on the basal metabolic activity of the
      bacilli detected.

PMID- 22360424
TI  - High false-negative rate of anti-HCV among Egyptian patients on regular
      hemodialysis.
AB  - Routine serological testing for hepatitis C virus (HCV) infection among
      hemodialysis (HD) patients is currently recommended. A dilemma existed on the
      value of serology because some investigators reported a high rate of false
      negative serologic testing. In this study, we aimed to detect the false-negative
      rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative
      for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA
      by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step,
      the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk
      factors for HCV infection, as well as clinical and biochemical indicators of
      liver disease, were compared between false-negative and true-negative anti-HCV HD
      patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood
      transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus
      were not identified as risk factors for HCV infection. The frequency of false
      negative results had a linear relation to the prevalence of HCV infection in the
      HD units. Timely identification of HCV within dialysis units is needed in order
      to lower the risk of HCV spread within the HD units. The high false-negative rate
      of anti-HCV among HD patients in our study justifies testing of a large scale of
      patients for precious assessment of effectiveness of nucleic acid amplification
      technology testing in screening HD patient.

PMID- 22360425
TI  - Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human
      macrophages.
AB  - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a
      highly evolved human pathogen characterized by its formidable cell wall. Many
      unique lipids and glycolipids from the Mtb cell wall are thought to be virulence
      factors that mediate host-pathogen interactions. An intriguing example is
      Sulfolipid-1 (SL-1), a sulfated glycolipid that has been implicated in Mtb
      pathogenesis, although no direct role for SL-1 in virulence has been established.
      Previously, we described the biochemical activity of the sulfotransferase Stf0
      that initiates SL-1 biosynthesis. Here we show that a stf0-deletion mutant
      exhibits augmented survival in human but not murine macrophages, suggesting that
      SL-1 negatively regulates the intracellular growth of Mtb in a species-specific
      manner. Furthermore, we demonstrate that SL-1 plays a role in mediating the
      susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite
      being dispensable for maintaining overall cell envelope integrity. Thus, we
      hypothesize that the species-specific phenotype of the stf0 mutant is reflective
      of differences in antimycobacterial effector mechanisms of macrophages.

PMID- 22360426
TI  - Liver transplantation for a patient with homocystinuria.
AB  - A 24-yr-old man was diagnosed with HCU during neonatal screening and remained on
      a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary
      methionine restriction for more than 10 yr. He had normal mental development,
      marfanoid appearance, myopia because of lens dislocation, and recurrent ankle
      subluxation during adolescence. Thereafter, he was a poor adherent to the
      conventional diet-restrictive therapy, and LT was considered when he developed
      hypertension and multiple infarctions over the right cerebellum early in the
      second decade of his life despite taking aspirin as a prophylaxis from 17 yr of
      age. In November 2009, he received a deceased whole LT from a blood group
      compatible donor. Along with the success of the transplantation, he was
      completely disease free without dietary or nutritional control. To the best of
      our knowledge, this is the first case of LT intended to cure HCU, and with
      promising results. This case provides an insight into the role of LT for this
      congenital metabolic disease, for which the decision should be made by judging
      between the severity of the disease and the risk of the operation, as well as the
      life quality of the patient.

PMID- 22360427
TI  - Bacteriogenic Fe(III) (oxyhydr)oxides characterized by synchrotron microprobe
      coupled with spatially resolved phylogenetic analysis.
AB  - Ubiquitous presence of microbes in aquatic systems and their inherent ability of
      biomineralization make them extremely important agents in the geochemical cycling
      of inorganic elements. However, the detailed mechanisms of environmental
      biomineralization (e.g., the actual reaction rates, the temporal and spatial
      dynamics of these processes) are largely unknown, because there are few adequate
      analytical techniques to observe the biogenic oxidation/reduction reactions in
      situ. Here, we report a novel technical approach to characterize specific
      biominerals associated with a target microbe on high spatial resolution. The
      technique was developed by combining directly in situ phylogenetic analysis,
      fluorescence in situ hybridization (FISH), with a synchrotron microprobe method,
      micro X-ray absorption fine structure spectroscopy (MU-XAFS), and was applied to
      iron mineral deposition by iron(II)-oxidizing bacteria (IOB) in environmental
      samples. In situ visualization of microbes revealed that in natural iron mats,
      Betaproteobacteria dominated by IOB were dominantly localized within 10 MUm of
      the surface. Furthermore, in situ chemical speciation by the synchrotron
      microprobe suggested that the Fe local structure at the IOB accumulating parts
      was dominantly composed of short-ordered Fe-O(6) linkage, which is not observed
      in bulk iron mat samples. The present study indicates that coupled XAFS-FISH
      could be a potential technique to provide direct information on specific biogenic
      reaction mediated by target microorganism.

PMID- 22360428
TI  - Behavior of pH-sensitive core shell particles at the air-water interface.
AB  - In this article, the adsorption of latex core-responsive polymer-shell
      nanoparticles at the air-water interface is investigated using a Langmuir trough.
      Phase transition isotherms are used to explore their responsive behavior at the
      interface as a function of changes in the pH of the subphase. By adjusting the pH
      of the water prior to particle deposition, we probe the effect of the stabilizing
      polymer wetting by the water subphase on the stability of these particles at the
      air-water interface. In addition, by initially compressing a stable film of
      adsorbed particles and then subsequently changing the pH of the subphase we study
      desorption of these particles into the water phase.

PMID- 22360429
TI  - The novel multi-target iron chelating-radical scavenging compound M30 possesses
      beneficial effects on major hallmarks of Alzheimer's disease.
AB  - AIMS: The aim of the present study was to evaluate the therapeutic effect of the
      novel neuroprotective multi-target nontoxic, lipophilic, brain permeable
      monoamine oxidase inhibitor and iron chelating-radical scavenging drug, M30, on
      the neuropathology and deficits of spatial learning and memory in amyloid
      precursor protein (APP) and presenilin 1 (PS1) double-transgenic (Tg) Alzheimer's
      disease (AD) mice. RESULTS: Here, we report that systemic treatment of APP/PS1 Tg
      mice with M30 for 9 months, significantly attenuated cognitive impairments in a
      variety of tasks of spatial learning and memory retention, working memory,
      learning abilities, anxiety levels, and memory for novel food and nesting
      behavior. Furthermore, we found that M30 reduced cerebral iron accumulation
      accompanied by a marked decrease in several AD-like phenotypes, including
      cerebral APP levels, amyloid beta (Abeta) levels and plaques, phospho-APP and
      phospho-tau. Signaling studies revealed that M30 markedly downregulated the
      levels of phosphorylated cyclin-dependent kinase 5 and increased protein kinase B
      and glycogen synthase kinase 3beta phosphorylation. INNOVATION: Accumulation and
      deposition of brain iron is central to various neuropathological processes in AD,
      including oxidative stress, amyloid deposition, and tau phosphorylation. Thus,
      the concept of iron chelation holds considerable promise as a therapeutic
      strategy for AD pathogenesis. Here, for the first time, we demonstrated that,
      when systemically administered to APP/PS1 Tg mice, our novel multifunctional iron
      chelating/radical scavenging compound, M30, effectively reduced Abeta
      accumulation and tau phosphorylation, and attenuated memory deficits.
      CONCLUSIONS: These findings suggest that M30 is a potential therapeutic agent for
      the prevention and treatment of AD.

PMID- 22360430
TI  - Overnight glucose infusion suppresses renal ammoniagenesis and reduces
      hyperammonaemia induced by a simulated bleed in cirrhotic patients.
AB  - BACKGROUND: A simulated upper gastrointestinal (UGI) bleed in cirrhotic patients
      has been shown to induce hyperammonaemia. The kidney was the site of this
      exaggerated ammoniagenesis with alanine as substrate. Administration of alanine
      to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but
      resulted in increased ammoniagenesis. We hypothesise that reduced hepatic
      glycogen stores result in hyperglucagonaemia which may drive increased renal
      gluconeogenesis and therefore alanine uptake and renal ammoniagenesis. AIM: To
      determine whether an overnight glucose infusion lowers renal ammoniagenesis by
      reducing hyperglucagonaemia and renal ammoniagenesis. METHODS: Patients with
      decompensated cirrhosis were studied in a cross-over design. An UGI bleed was
      simulated via intragastric administration of an amino acids mixture mimicking the
      haemoglobin molecule after a 12-h overnight fast (F-group) or after a 12-h
      treatment with 20% glucose solution (G-group). RESULTS: Before the simulated
      bleed the glucagon levels were 21 (15-31) pmol/L in the F-group and 15 (9-21)
      pmol/L in the G-group (P < 0.01). After the simulated bleed, arterial ammonia
      levels increased in both groups [F-group: 73-118 MUmol/L (P = 0.01); G-group 64
      87 MUmol/L (P = 0.01)]. The enhancement of hyperammonaemia was significantly
      higher in the F-group (45 [19-71] MUmol/L) compared with the G-group (23 [13-39]
      MUmol/L) (P = 0.01). The difference in renal ammoniagenesis during the simulated
      bleed in the F-group was 399 (260-655) nmol/kg/bwt/min and was significantly
      higher than in the G-group 313 (1-498) nmol/kg/bwt/min (P = 0.05). CONCLUSIONS:
      Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates
      ammonia levels. These observations have implications for the development of
      nutritional strategies in hyperammonaemic patients.

PMID- 22360431
TI  - A series of octanuclear-nickel(II) complexes supported by thiacalix[4]arenes.
AB  - A series of discrete complexes, [Ni(8)(BTC4A)(2)(MU(6)-CO(3))(2)(MU
      CH(3)COO)(4)(dma)(4)].H(2)O (1), [Ni(8)(BTC4A)(2)(MU(6)-CO(3))(2)(MU-Cl)(2)(MU
      HCOO)(2)(dma)(4)].2DMF.2CH(3)CN (2), [Ni(8)(PTC4A)(2) (MU(6)-CO(3))(2)(MU
      CH(3)COO)(4)(dma)(4)].DMF (3), and [Ni(8)(PTC4A)(2)(MU(6)-CO(3))(2)(MU-OH)(MU
      HCOO)(3) (dma)(4)] (4) (p-tert-butylthiacalix[4]arene = H(4)BTC4A, p
      phenylthiacalix[4]arene = H(4)PTC4A, dma = dimethylamine, and DMF = N,N'
      dimethylformamide), have been prepared under solvothermal conditions and
      structurally characterized by single-crystal X-ray diffraction analyses, powder
      XRD, and IR spectroscopy. These four complexes are stacked by dumbbell-like
      building blocks with one chairlike octanuclear-nickel(II) core, which is capped
      by two thiacalix[4]arene molecules and connected by two in situ generated
      carbonato anions and different auxiliary anions. This work implied that not only
      the solvent molecules but also the upper-rim groups of thiacalix[4]arenes have
      significant effects on the self-assembly of the dumbbell-like building blocks.
      The magnetic properties of complexes 1-4 were examined, indicating strong
      antiferromagnetic interactions between the nickel(II) ions in the temperature
      range of 50-300 K.

PMID- 22360432
TI  - Under what conditions would people be willing to make a living organ donation?
AB  - The aim was to examine the factors involved in people's willingness to make a
      living organ donation. A convenience sample of 200 people in southern France
      rated willingness to be a living donor in 48 scenarios consisting of all
      combinations of five factors: recipient's identity (close family member and city
      resident); donor's surgical risk (little and some); donor's possible long-term
      health consequences (none, some lessening over time, and durable); transplant
      success ("generally durably successful" and "durably successful one time out of
      two"); and likelihood of other donors (subject is one of the rare compatible
      donors or one among others). Cluster analyses showed the existence of three
      distinct organ donation philosophies. For the largest cluster (49% of
      participants), willingness to donate was very high to a family member, but low to
      a city resident. For the second cluster (37%), willingness was high to family,
      but also moderately high to a city resident. For the third cluster (14%),
      willingness was always low. Thus, most participants judged themselves ready to
      make a living organ donation to a family member and many even to a stranger.

PMID- 22360433
TI  - Packing a pinch: functional implications of chela shapes in scorpions using
      finite element analysis.
AB  - Scorpions depend on their pedipalps for prey capture, defense, mating and sensing
      their environment. Some species additionally use their pedipalps for burrowing or
      climbing. Because the pincers or chelae at the end of the pedipalps vary widely
      in shape, they have been used as part of a suite of characters to delimit
      ecomorphotypes. We here evaluate the influence of the different chela cuticular
      shapes on their performance under natural loading conditions. Chelae of 20
      species, representing seven families and spanning most of the range of chela
      morphologies, were assigned to clusters based on chela shape parameters using
      hierarchical cluster analysis. Several clusters were identified corresponding
      approximately to described scorpion ecomorphotypes. Finite element models of the
      chela cuticulae were constructed from CT scans and loaded with estimated pinch
      forces based on in vivo force measurements. Chela shape clusters differed
      significantly in mean Von Mises stress and strain energy. Normalized FEA showed
      that chela shape significantly influenced Von Mises stress and strain energy in
      the chela cuticula, with Von Mises stress varying up to an order of magnitude and
      strain energy up to two orders of magnitude. More elongate, high-aspect ratio
      chela forms showed significantly higher mean stress compared with more robust low
      aspect ratio forms. This suggests that elongate chelae are at a higher risk of
      failure when operating near the maximum pinch force. Phylogenetic independent
      contrasts (PIC) were calculated based on a partly resolved phylogram with branch
      lengths based on an alignment of the 12S, 16S and CO1 mitochondrial genes. PIC
      showed that cuticular stress and strain in the chela were correlated with several
      shape parameters, such as aspect ratio, movable finger length, and chela height,
      independently of phylogenetic history. Our results indicate that slender chela
      morphologies may be less suitable for high-force functions such as burrowing and
      defense. Further implications of these findings for the ecology and evolution of
      the different chela morphologies are discussed.

PMID- 22360434
TI  - Streptococcal pharyngitis leading to corneal ulceration.
AB  - PURPOSE: To report a patient with a history of exposure keratopathy who presented
      with bilateral bacterial keratitis associated with streptococcal pharyngitis and
      use of bilevel positive airway pressure (BiPAP). DESIGN: Case report. METHODS:
      Pulsed-field gel electrophoresis of patient isolates from ocular and pharyngeal
      cultures. RESULTS: Ocular and oropharyngeal cultures from a 24-month-old child
      with a history of cerebral palsy on BiPAP at night revealed the same strain of
      Streptococcus pyogenes. CONCLUSIONS: Use of mechanical ventilation, such as
      BiPAP, may precipitate inoculation of eye with respiratory or oropharyngeal
      pathogens. To the authors' knowledge this is the first report demonstrating the
      association between concurrent streptococcal pharygitis, keratitis, and use of
      BiPAP.

PMID- 22360435
TI  - Uveitis treatment trials--a cross-study perspective.

PMID- 22360436
TI  - Metal-assisted Lossen rearrangement.
AB  - A new reaction mechanism for the Lossen rearrangement of hydroxamic acids
      catalyzed by basic salts is presented. It is shown that the rearrangement
      proceeds in metal complexes of deprotonated hydroxamic acids. The deprotonation
      can occur either at the oxygen atom (observed for the zinc complexes) or at the
      nitrogen atom (observed for the potassium complexes). Both anionic forms are
      characterized by infrared multiphoton dissociation spectroscopy. The
      rearrangements proceed from the reactive N-deprotonated metal hydroxamates and
      lead to metal carbamates. The mechanism is elucidated by computational chemistry,
      mass-spectrometric studies, and preparative experiments.

PMID- 22360437
TI  - Editorial comment for Sharib et al.

PMID- 22360438
TI  - Pregnancy and a rare MTHFR haplotype.

PMID- 22360439
TI  - The effect of hemodialysis ultrafiltration on changes in whole blood viscosity.
AB  - Increased whole blood viscosity (WBV) can be injurious to the vascular
      endothelium and increase the risk of atherothrombotic events. This study examined
      the effect of hemodialysis ultrafiltration (UF) on WBV, with a focus on high vs.
      low-volume UF patients. In stable hemodialysis patients, blood was drawn for
      hematocrit (Hct) and WBV at the start, midpoint, and at the end of dialysis. For
      analysis, patients were divided into high UF (>=2700 mL) or low UF (<2700 mL)
      groups. A total of 59 patients completed the study. Mean Hct increased during
      dialysis in both groups. The intradialytic increase in Hct was significantly
      greater in the high vs. the low UF group (3.2% vs. 1.28%, P = 0.01), with a
      significantly higher end-dialysis Hct in the high UF group (40.5% vs. 38%, P =
      0.02). At the end of dialysis, both high shear rate WBV (P < 0.01) and low shear
      rate WBV (P < 0.01) were significantly higher in the high UF compared with the
      low UF group. There was an approximately two-fold greater increase in high shear
      rate (P < 0.01) and low shear rate (P = 0.01) WBV during dialysis in high vs. low
      UF groups. The increase in high shear rate WBV during dialysis was significantly
      correlated with an increase in Hct (R(2) = 0.63, P < 0.01). We found that
      hemodialysis UF causes a surge in WBV. The surge was of greater magnitude in high
      than in low UF patients.

PMID- 22360440
TI  - Xanthohumol impairs autophagosome maturation through direct inhibition of valosin
      containing protein.
AB  - Autophagy is a bulk, nonspecific protein degradation pathway that is involved in
      the pathogenesis of cancer and neurodegenerative disease. Here, we observed that
      xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and
      beer, modulates autophagy. By using XN-immobilized beads, valosin-containing
      protein (VCP) was identified as a XN-binding protein. VCP has been reported to be
      an essential protein for autophagosome maturation. Using an in vitro pull down
      assay, we showed that XN bound directly to the N domain, which is known to
      mediate cofactor and substrate binding to VCP. These data indicated that XN
      inhibited the function of VCP, thereby allowing the impairment of autophagosome
      maturation and resulting in the accumulation of microtubule-associated protein 1
      light chain 3-II (LC3-II). This is the first report demonstrating XN as a VCP
      inhibitor that binds directly to the N domain of VCP. Our finding that XN bound
      to and inactivated VCP not only reveals the molecular mechanism of XN-modulated
      autophagy but may also explain how XN exhibits various biological activities that
      have been reported previously.

PMID- 22360441
TI  - Susceptibility to ankylosing spondylitis but not disease outcome is influenced by
      the level of HLA-B27 expression, which shows moderate variability over time.
AB  - OBJECTIVE: Previous reports have highlighted the relevance of HLA-B27 expression
      in the pathogenesis of ankylosing spondylitis (AS). The aim of the current study
      was to estimate the level of HLA-B27 expression on the cell surface of ex vivo
      monocytes and lymphocytes by a quantitative method and to correlate this with AS
      disease susceptibility, disease clinical indexes, and the occurrence of acute
      anterior uveitis (AAU). METHOD: We recruited 32 B27-positive patients with AS and
      32 B27-positive healthy normal controls (NCs) for evaluation at different time
      points. The expression of HLA-B27 molecules was quantified by flow cytometry on
      ex vivo peripheral blood mononuclear cells (PBMCs). Patients were also evaluated
      by scores on the Bath AS disease activity (BASDAI), functional (BASFI), and
      metrology (BASMI) indexes. RESULTS: The expression of HLA-B27 molecules was
      significantly higher in patients with AS than in B27-matched controls in the case
      of both monocytes [219K (IQR 174K-308K) vs. 137K (IQR 96K-170K), p < 0.0001] and
      lymphocytes [82K (IQR 58K-118K) vs. 54K (IQR 44K-61K), p < 0.0001]; AS only vs.
      AS with AAU: p = 0.744 in monocytes and p = 0.701 in lymphocytes. Comparisons
      with metrology and functional indexes were also not significant (BASMI: r = 0.05,
      p = 0.77; BASFI: r = -0.09, p = 0.67). The overexpression of HLA-B27 molecules
      was stable after 1 week of follow-up. At 3 years follow-up, the variability was
      moderate and did not correlate with variations in disease activity (BASDAI: r = 
      0.01, p = 0.92 ns). CONCLUSIONS: The level of HLA-B27 expression in PBMCs
      correlates with the susceptibility to AS but not with the disease outcome, nor
      with the occurrence of extra-articular manifestations such as AAU.

PMID- 22360442
TI  - Efficient dechlorination of carbon tetrachloride by hydrophobic green rust
      intercalated with dodecanoate anions.
AB  - The reductive dechlorination of carbon tetrachloride (CT) by Fe(II)-Fe(III)
      hydroxide (green rust) intercalated with dodecanoate,
      Fe(II)(4)Fe(III)(2)(OH)(12)(C(12)H(23)O(2))(2) . yH(2)O (designated GR(C12)), at
      pH ~ 8 and at room temperature was investigated. CT at concentration levels
      similar to those found in heavily contaminated groundwater close to polluted
      industrial sites (14-988 MUM) was reduced mainly to the fully dechlorinated
      products carbon monoxide (CO, yields >54%) and formic acid (HCOOH, yields >6%).
      Minor formation of chloroform (CF), the only chlorinated degradation product, was
      also detected (yields <6.3%). Reactions carried out with excess GR followed
      pseudo first-order kinetics with respect to CT with rate constants ranging from
      6.5 * 10(-2) to 0.47 h(-1). These rate constants are comparable to those measured
      for CT dechlorinations mediated by zerovalent iron. Reduction of the highest
      concentration of CT (1.4 mM) proceeds until 56% of the Fe(II) sites of GR(C12)
      was consumed. This reaction ceased after 10 h due to surface passivation of
      GR(C12).

PMID- 22360443
TI  - Fall Risk Index predicts functional decline regardless of fall experiences among
      community-dwelling elderly.
AB  - AIM: The 21-item Fall Risk Index (FRI-21) has been used to detect elderly persons
      at risk for falls. The aim of this longitudinal study was to evaluate the FRI-21
      as a predictor of decline in basic activities of daily living (BADL) among
      Japanese community-dwelling elderly persons independent of fall risk. METHODS:
      The study population consisted of 518 elderly participants aged 65 years and
      older who were BADL independent at baseline in Tosa, Japan. We examined risk
      factors for BADL decline from 2008 to 2009 by multiple logistic regression
      analysis on the FRI-21 and other functional status measures in all participants.
      We carried out the same analysis in selected participants who had no experience
      of falls to remove the effect of falls. RESULTS: A total of 45 of 518
      participants showed decline in BADL within 1 year. Multivariate logistic
      regression analysis showed that age (odds ratio [OR] 1.13, 95% confidence
      interval [CI] 1.05-1.20), FRI-21 >= 10 (OR 3.81, 95% CI 1.49-9.27), intellectual
      activity dependence (OR 3.25, 95% CI 1.42-7.44) and history of osteoarthropathy
      (OR 3.17, 95% CI 1.40-7.21) were significant independent risk factors for BADL
      decline within 1 year. FRI-21 >= 10 and intellectual activity dependence (<= 3)
      remained significant predictors, even in selected non-fallers. CONCLUSION: FRI-21
      >= 10 and intellectual activity dependence were significant predictive factors of
      BADL decline, regardless of fall experience, after adjustment for confounding
      variables. The FRI-21 is a brief, useful tool not only for predicting falls, but
      also future decline in functional ability in community-dwelling elderly persons.

PMID- 22360445
TI  - Synthesis and characterization of Th2N2(NH) isomorphous to Th2N3.
AB  - Using a new, low-temperature, fluoride-based process, thorium nitride imide of
      the chemical formula Th(2)N(2)(NH) was synthesized from thorium dioxide via an
      ammonium thorium fluoride intermediate. The resulting product phase was
      characterized by powder X-ray diffraction (XRD) analysis and was found to be
      crystallographically similar to Th(2)N(3). Its unit cell was hexagonal with a
      space group of P3m1 and lattice parameters of a = b = 3.886(1) and c = 6.185(2)
      A. The presence of -NH in the nitride phase was verified by Fourier transform
      infrared spectroscopy (FTIR). Total energy calculations performed using all
      electron scalar relativistic density functional theory (DFT) showed that the
      hydrogen atom in the Th(2)N(2)(NH) prefers to bond with nitrogen atoms occupying
      1a Wyckoff positions of the unit cell. Lattice fringe disruptions observed in
      nanoparticle areas of the nitride species by high-resolution transmission
      electron microscopic (HRTEM) images also displayed some evidence for the presence
      of -NH group. As ThO(2) was identified as an impurity, possible reaction
      mechanisms involving its formation are discussed.

PMID- 22360444
TI  - (Thio)ureido anion receptors based on a 1,3-alternate
      oxacalix[2]arene[2]pyrimidine scaffold.
AB  - In pursuit of highly preorganized macrocyclic host molecules for the complexation
      of anions, a series of oxacalix[2]arene[2]pyrimidine-based bis(thio)ureido
      receptors were synthesized and fully characterized. The pincer-like 1,3-alternate
      conformation of the oxacalix[4]arene scaffold, essential for an efficient host
      guest interaction, was visualized by single-crystal X-ray analysis and supported
      by variable-temperature NMR studies. The anion binding properties of the
      receptors were evaluated via (1)H NMR titration experiments, showing
      intermolecular interactions with H(2)PO(4)(-), AcO(-), BzO(-), and Cl(-) ions.
      The host molecule bearing 4-nitrophenyl substituents on the bisurea binding
      pocket showed association constants in the range of 200-400 M(-1) in the strongly
      competitive solvent mixture of DMSO/0.5% H(2)O.

PMID- 22360447
TI  - Prediction of drug concentration-time data in humans from animals: a comparison
      of three methods.
AB  - The main objective of this work is to evaluate three methods to predict
      concentration-time data of drugs in humans in a multi-compartment system using
      animal pharmacokinetic parameters following intravenous administration. The
      prediction of concentration-time data in humans in a multi-compartment system was
      based on two proposed methods of Mordenti. The third method was based on the
      assumption that all drugs follow a single-compartment system. Ten drugs from the
      literature were chosen that were described by two-compartment model in both human
      and animals. Two-compartment model parameters (CL, V(c), V(ss), V(beta), alpha,
      A, beta and B) of at least 3 animals were scaled to humans and then were used to
      predict plasma concentrations-time data in humans. Allometrically scaled
      pharmacokinetic parameters from animals were also used to predict human profile
      using one-compartment model as a comparison. The results indicated that in a
      multi-compartment system, application of pharmacokinetic constants provided
      better prediction of concentration-time data in humans than the assumption that
      all drugs follow a single-compartment model. Both the proposed methods of
      Mordenti provided almost similar concentration-time profiles for most of the
      drugs. For some drugs, predicted alpha values were substantially higher than the
      observed values. This prediction error in alpha resulted in under-prediction of
      drug concentrations in distribution phase. In order to reduce the prediction
      error in alpha, Waijma's method for the prediction of alpha was modified which
      resulted in an improved prediction of concentration-time data in humans. Overall,
      Mordenti's proposed 2 methods and where necessary by modifying Waijma's method
      for the prediction of alpha can be used for reasonably accurate prediction of
      concentration-time data of drugs in humans.

PMID- 22360446
TI  - Evaluation of the Xpert Flu test and comparison with in-house real-time RT-PCR
      assays for detection of influenza virus from 2008 to 2011 in Marseille, France.
AB  - Rapid documentation of respiratory specimens can have an impact on the management
      of patients and their relatives in terms of preventive and curative measures. We
      compared the results of the Xpert((r)) Flu assay (Cepheid) with three real-time
      RT-PCR assays using 127 nasopharyngeal samples, of which 75 were positive for
      influenza A (with 52 identified as A/H1N1-2009) and 52 were positive for
      influenza B. The Xpert((r)) Flu assay presented a quasi-absence of non
      interpretable tests, and showed sensitivity and specificity of 100% and 100% for
      Flu A, 98.4% and 100% for A/H1N1-2009, and 80.7% and 100% for Flu B.

PMID- 22360448
TI  - Rosuvastatin suppresses the liver microsomal CYP2C11 and CYP2C6 expression in
      male Wistar rats.
AB  - The aim was to investigate whether rosuvastatin affect rat cytochrome P450 (CYP)
      2C11 and CYP2C6. CYP2C11 and CYP2C6 are considered as counterparts of human
      CYP2C9, which metabolizes many drugs including S-warfarin, diclofenac or
      ibuprofen. The male Wistar rats were fed standard laboratory diet (STD) or high
      cholesterol diet (HCD, 1% of cholesterol, 10% of lard fat) for 21 days.
      Rosuvastatin administration in STD (0.03% w/w) resulted in decreased mRNA
      expression of CYP2C11 as well as of CYP2C6 (here significant) and in a
      significant decrease of the respective protein expression as well as of the
      enzyme activity of both CYP2C forms. When rosuvastatin was administered in the
      HCD, the mRNA expression of both CYP2C forms was significantly lowered; the
      protein and activity parameters did not show significant changes. These results
      suggest that CYP2C11 as well as CYP2C6 expression and activity are negatively
      affected by rosuvastatin and may be modulated by high cholesterol high fat diet.
      Therefore, it should be taken into consideration that drugs metabolized by CYP2C9
      in human could interact with rosuvastatin, as it has been already suggested for
      warfarin (rosuvastatin has increased its anticoagulant effect in human), and for
      telmisartan, sildenafil and glimepiride.

PMID- 22360449
TI  - Coverage of hospital-based cataract surgery and barriers to the uptake of surgery
      among cataract blind persons in nigeria: the Nigeria National Blindness and
      Visual Impairment Survey.
AB  - PURPOSE: To determine cataract surgical coverage, and barriers to modern cataract
      surgery in Nigeria. METHODS: Multistage stratified cluster random sampling was
      used to identify a nationally representative sample of 15,027 persons aged 40+
      years. All underwent visual acuity testing, frequency doubling technology visual
      field testing, autorefraction, and measurement of best corrected vision if <6/12
      in one or both eyes. An ophthalmologist examined the anterior segment and fundus
      through an undilated pupil for all participants. Participants were examined by a
      second ophthalmologist using a slit lamp and dilated fundus examination using a
      90 diopter condensing lens if vision was <6/12 in one or both eyes, there were
      optic disc changes suggestive of glaucoma, and 1 in 7 participants regardless of
      findings. All those who had undergone cataract surgery were asked where and when
      this had taken place. Individuals who were severely visually impaired or blind
      from unoperated cataract were asked to explain why they had not undergone
      surgery. RESULTS: A total of 13,591 participants were examined (response rate
      89.9%). Prevalence of cataract surgery was 1.6% (95% confidence interval 1.4
      1.8), significantly higher among those aged >=70 years. Cataract surgical
      coverage (persons) in Nigeria was 38.3%. Coverage was 1.7 times higher among
      males than females. Coverage was only 9.1% among women in the South-South
      geopolitical zone. Over one third of those who were cataract blind said they
      could not afford surgery (36%). CONCLUSIONS: Cataract surgical coverage in
      Nigeria was among the lowest in the world. Urgent initiatives are necessary to
      improve surgical output and access to surgery.

PMID- 22360450
TI  - Integrating pharmacology and clinical pharmacology in pharmaceutical companies.
AB  - Integration of clinical and preclinical pharmacology in pharmaceutical companies
      could be improved by several key recommendations: Companies should ensure that
      there is an adequate pool of trained clinical pharmacologists and preclinical
      pharmacologists. Training should include topics that allow clinical
      pharmacologists to be cognizant of the methods, issues and challenges faced by
      the preclinical pharmacologists and vice versa. Companies should incentivize such
      integration internally by aligning objectives and metrics/incentives. In academic
      medicine and the NHS there should be support for involvement of clinical
      pharmacologists in basic academic research and industrial R & D and new ways of
      facilitating and incentivizing preclinical pharmacologists and clinical
      pharmacologists to move between these various environments should be sought.

PMID- 22360451
TI  - Ieodoglucomides A and B from a marine-derived bacterium Bacillus licheniformis.
AB  - Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino
      acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine
      derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2
      was determined by deploying coupling constants, Marfey's and Mosher's methods,
      and literature reviews. Compounds 1 and 2 displayed moderate in vitro
      antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic
      activity against lung cancer and stomach cancer cell lines with GI(50) values of
      25.18 and 17.78 MUg/mL, respectively.

PMID- 22360452
TI  - Testosterone, oestradiol and insulin sensitivity in men.

PMID- 22360453
TI  - Cosmopolitanism of microbial eukaryotes in the global deep seas.
AB  - Deep sea environments cover more than 65% of the earth's surface and fulfil a
      range of ecosystem functions, yet they are also amongst the least known habitats
      on earth. Whilst the discovery of key geological processes, combined with
      technological developments, has focused interest onto geologically active areas
      such as hydrothermal vents, most abyssal biodiversity remains to be discovered
      (Danovaro et al. 2010). However, as for terrestrial reservoirs of biodiversity,
      the world's largest biome is under threat from anthropogenic activities ranging
      from environmental change to the exploitation of minerals and rare-earth elements
      (Kato et al. 2011). It is therefore important to understand the magnitude, nature
      and composition of deep sea biological communities to inform us of levels of
      local adaptation, functionality and resilience with respect to future
      environmental perturbation. In this issue of Molecular Ecology, Bik et al.
      utilize 454 Roche metagenetic environmental sequencing to assess microbial
      metazoan community composition and phylogenetic identity across deep sea depth
      gradients and between ocean basins. The analyses suggest that although the
      majority of microbial eukaryotic taxa are regionally restricted, a small
      percentage might maintain cosmopolitan deep sea distributions, and an even
      smaller fraction appear to be eurybathic (live across depth gradients).

PMID- 22360454
TI  - Out in the cold--how big and how old? Genetic fingerprinting reveals long-lived
      individuals withstand climatic oscillations in the arctic-alpine.
AB  - In long-lived, clonally reproducing species, assessing organism size is a
      nontrivial endeavour because each genetically distinct entity (genet) may
      comprise multiple modular units (ramets). Attributes of clonally reproducing
      populations, such as genet size, longevity and clonal diversity (the number of
      genets in a population), have significant implications for the persistence of
      populations over time. In the context of climate change, population persistence
      contributes to community stability and ecosystem resilience. Do clonal
      individuals persist through periods of climatic oscillations? Are clonal
      populations composed of a few large and persistent clones, or do they include
      clones of different sizes and ages? In this issue, de Witte et al. (2012) present
      an exciting analysis of clonal diversity and genet longevity in populations of
      four arctic-alpine plant species with contrasting life histories: Carex curvula,
      Dryas octopetala, Salix herbacea and Vaccinium uliginosum. Using amplified
      fragment length polymorphism (AFLP) data, the authors demonstrate that genet size
      ranged from a few centimetres to 18 metres and age estimates for the largest
      genets ranged from 500 to 4900 years. These data reveal that clonally reproducing
      populations include individuals that have outlived significant changes in
      climate. Despite the longevity of some individuals, clonal diversity within
      populations was high, with most individuals existing as small, relatively young
      genets. Long-lived individuals, together with high numbers of younger plants,
      ensure repeated recruitment and population persistence over time. This study
      represents a novel and timely contribution to a growing body of work aimed at
      understanding population persistence in changing climates.

PMID- 22360455
TI  - Vineyard and fermentation studies to elucidate the origin of 1,8-cineole in
      Australian red wine.
AB  - Preliminary investigations revealed that the proximity of  Eucalyptus  trees to
      grapevines can directly influence the concentration of the aroma compound 1,8
      cineole present in the corresponding red wines. For two different vineyards, the
      closer the grapevines were to the trees, the greater was the amount of 1,8
      cineole in the wines elaborated from those grapes. This led us to carry out
      further studies to quantify the levels of 1,8-cineole found in grape berries,
      leaves, and stems at set distances from  Eucalyptus  trees over multiple
      vintages. Generally, the highest concentration of 1,8-cineole was found in the
      grapevine leaves, followed by grape stems and then grapes. In each sample type,
      we observed greater concentrations of 1,8-cineole in samples closer to the trees.
      Various fermentation treatments carried out with Shiraz grapes showed that matter
      other than grapes (MOG, e.g.,  Eucalyptus  or grape leaves) could contribute
      significant amounts of 1,8-cineole to the finished wines. These studies confirmed
      that vineyard position and winemaking conditions can determine the 1,8-cineole
      concentration in red wine. The fermentation study also showed for the first time
      that the concentration of rotundone in red wine can be strongly influenced by
      grapevine leaves and stems in the ferment.

PMID- 22360456
TI  - Polyelectrolyte adsorption: electrostatic mechanisms and nonmonotonic responses
      to salt addition.
AB  - The main question addressed in this work is as follows: Under pure
      electrosorption conditions, that is, disregarding nonelectrostatic effects, how
      does the net adsorption of a polyelectrolyte at an oppositely charged surface
      respond to the addition of simple salt? Previous simulations and mean-field
      calculations have suggested that the polymers will desorb. However, we will
      demonstrate that an increased adsorption also is possible, even for pure
      electrosorption, at low and intermediate levels of salt. As this is a correlation
      driven effect, mean field approaches will fail to capture it. Using simulations,
      one will in general need to simulate large systems and relatively long polymers.
      Also important is the presence of a proper bulk solution, with a finite and well
      defined polyelectrolyte concentration. We have performed a theoretical study of
      polyelectrolyte adsorption, assuming screened Coulomb interactions between
      monomers; that is, the salt is implicit. This work focuses on the effects from
      ionic screening and polymer length. Specifically, the adsorption at a weakly
      charged colloidal particle, with a diameter of 200 nm, is monitored for various
      salt concentrations, in the presence of highly charged chains. Using simulations,
      we investigate polymers with two different degrees of polymerization: 40 and 160,
      respectively. These simulations are complemented by predictions from classical
      polymer density functional theory, utilizing a recently developed correlation
      correction (Forsman, J.; Nordholm, S. Langmuir, in press). The agreement with
      corresponding simulations is semiquantitative, and because the calculations run
      many orders of magnitude faster than the simulations, longer and more realistic
      polymers could be studied with this approach. However, switching off the
      correlation-correction leads to a mean-field theory, which fails to even
      qualitatively reproduce the simulated response to screening.

PMID- 22360457
TI  - Being at risk for cardiovascular disease: perceptions and preventive behavior in
      people with and without a known genetic predisposition.
AB  - This study compares and explains differences in perceptions of cardiovascular
      disease (CVD) risk and preventive behaviors in people with and without a known
      genetic predisposition to CVD. A cross-sectional study using two samples was
      performed. The first sample (genetic predisposition; n = 51) consisted of
      individuals recently diagnosed with familial hypercholesterolemia (FH) through
      DNA testing. The second sample (no genetic predisposition; n = 49) was recruited
      among patients with CVD-risk profiles based on family history of CVD, cholesterol
      levels, and blood pressure, registered at general practices. Participants filled
      out a postal questionnaire asking about their perceived risk, causal attributions
      (i.e. genetic and lifestyle), and about perceived efficacy and adoption of
      preventive behavior (i.e. medication adherence and adoption of a healthy diet and
      being sufficiently active). Perceived comparative risk, genetic attributions of
      CVD, and perceived efficacy of medication were higher in the "genetic
      predisposition" sample than in the "no genetic predisposition" sample. The
      samples did not differ on lifestyle attributions, efficacy of a healthy
      lifestyle, or preventive behavior. Individual differences in perceived risk,
      genetic attributions, perceived efficacy of medication, and adoption of a healthy
      lifestyle were best explained by family history of CVD. Our findings suggest that
      in people diagnosed with a single gene disorder characterized by a family disease
      history such as FH, family disease history may be more important than DNA
      information in explaining perceptions of and responses to risk.

PMID- 22360458
TI  - Study of the three-dimensional orientation of the labrum: its relations with the
      osseous acetabular rim.
AB  - Understanding the three-dimensional orientation of the coxo-femoral joint remains
      a challenge as an accurate three-dimensional orientation ensure an efficient
      bipedal gait and posture. The quantification of the orientation of the acetabulum
      can be performed using the three-dimensional axis perpendicular to the plane that
      passes along the edge of the acetabular rim. However, the acetabular rim is not
      regular as an important indentation in the anterior rim was observed. An
      innovative cadaver study of the labrum was developed to shed light on the proper
      quantification of the three-dimensional orientation of the acetabulum.
      Dissections on 17 non-embalmed corpses were performed. Our results suggest that
      the acetabular rim is better represented by an anterior plane and a posterior
      plane rather than a single plane along the entire rim as it is currently assumed.
      The development of the socket from the Y-shaped cartilage was suggested to
      explain the different orientations in these anterior and posterior planes. The
      labrum forms a plane that takes an orientation in between the anterior and
      posterior parts of the acetabular rim, filling up inequalities of the bony rim.
      The vectors V(L) , V(A2)  and V(P) , representing the three-dimensional
      orientation of the labrum, the anterior rim and the posterior rim, are situated
      in a unique plane that appears biomechanically dependent. The three-dimensional
      orientation of the acetabulum is a fundamental parameter to understand the hip
      joint mechanism. Important applications for hip surgery and rehabilitation, as
      well as for physical anthropology, were discussed.

PMID- 22360459
TI  - Barbed compared with standard suture: effects on cellular composition and
      proliferation of the healing wound in the ovine uterus.
AB  - OBJECTIVE: To compare cellular composition (fibroblasts vs. smooth muscle cells)
      and proliferation in uterine healing wounds after application of barbed compared
      with standard suture in a sheep model. DESIGN: Randomized trial (Canadian Task
      Force classification I) using each animal as its own control. SETTING: Certified
      animal research facility. Population or sample. 23 non-pregnant ewes. METHODS: A
      myometrial incision was created with the harmonic scalpel in each horn of the
      bicornuate uterus. The incisions were randomly allocated to be closed using
      either polyglactin 210 (Vicryl(r)) or barbed suture. Three months later, uterine
      tissues were collected, fixed and used for determination of cellular composition
      and proliferation using histochemistry (Masson trichrome staining) and
      immunohistochemistry (staining of smooth muscle cell actin and Ki67, a marker of
      proliferating cells) followed by image analysis. MAIN OUTCOME MEASURES:
      Evaluation and comparison of the cellular composition and proliferation of
      uterine wounds after application of barbed vs. standard suture. RESULTS: The
      ratio between connective tissue elements and smooth muscle cells, expression of
      smooth muscle cell actin and labeling index were similar in wounds after
      application of barbed compared with standard suture, but were different (p <
      0.0001-0.05) in wounds than in non-wounded areas in uterus. CONCLUSION: Both
      barbed and standard sutures had similar effects on cellular composition and
      proliferation of uterine wounds in an animal model.

PMID- 22360460
TI  - Similar outcomes of catheters implanted by nephrologists and surgeons: analysis
      of the Brazilian peritoneal dialysis multicentric study.
AB  - A good catheter implantation technique is important to allow for effective
      peritoneal access function and long-term technique survival. Studies regarding
      results obtained by nephrologists in comparison with surgeons have been limited
      to small single-center experiences. Thus, the objective of this study was to
      explore the impact of the peritoneal dialysis (PD) catheter insertion operator on
      early catheter complications and on technique survival in a large national
      multicentric cohort study (Brazilian Peritoneal Dialysis Multicentric Study,
      BRAZPD). Adult incident patients recruited in the BRAZPD from December 2004 to
      October 2007 having undergone first PD catheter implantation were included in the
      analysis. Mechanical and infectious early complication rates were defined as time
      to the first event occurring up to 3 months after catheter insertion and adjusted
      for comorbidities. Valid data of 736 patients (mean age of 59 +/- 16 years old,
      52% women, 61% white) were analyzed. Mechanical (HR 0.99 [CI 0.56-1.76]; p =
      0.98) and infectious (HR 0.63 [CI 0.32-1.23]; p = 0.17) early complication rates
      were similar between groups. Long-term catheter survival was also similar between
      groups. Early complications rates and catheter survival were similar between
      groups defined by operator profile (nephrologist or surgeon), supporting the role
      of interventional nephrology in the placement of PD catheters.

PMID- 22360461
TI  - Copper-catalyzed asymmetric oxidation of sulfides.
AB  - Copper-catalyzed asymmetric sulfoxidation of aryl benzyl and aryl alkyl sulfides,
      using aqueous hydrogen peroxide as the oxidant, has been investigated. A
      relationship between the steric effects of the sulfide substituents and the
      enantioselectivity of the oxidation has been observed, with up to 93% ee for 2
      naphthylmethyl phenyl sulfoxide, in modest yield in this instance (up to 30%).
      The influence of variation of solvent and ligand structure was examined, and the
      optimized conditions were then used to oxidize a number of aryl alkyl and aryl
      benzyl sulfides, producing sulfoxides in excellent yields in most cases (up to
      92%), and good enantiopurities in certain cases (up to 84% ee).

PMID- 22360462
TI  - The neuroprotection of hydrogen sulfide against MPTP-induced dopaminergic neuron
      degeneration involves uncoupling protein 2 rather than ATP-sensitive potassium
      channels.
AB  - AIMS: Hydrogen sulfide (H(2)S), a novel gaseous mediator, has been recognized to
      protect neurons from overexcitation by enhancing the activity of the adenosine
      triphosphate-sensitive potassium (K-ATP) channel. However, no direct evidence
      supports that the K-ATP channel contributes to the neuroprotective effect of
      H(2)S in neurodegeneration. Herein, wild-type and Kir6.2 knockout (Kir6.2(-/-))
      mice were used to establish the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) mouse model of Parkinson's disease (PD) so as to investigate the
      involvement of K-ATP channels in the neuroprotection of H(2)S. RESULTS: Systemic
      administration of sodium hydrosulfide (NaHS) (an H(2)S donor, 5.6 mg/kg/day) for
      7 days rescued MPTP-induced loss of dopaminergic (DA) neurons in substantia nigra
      compacta of both Kir6.2(+/+) and Kir6.2(-/-) mice. Consistently, NaHS (100 MUM)
      protected primary mesencephalic neurons against 1-methyl-4-phenylpyridinium
      (MPP(+))-induced cytotoxicity in both genotypes. We further found that deficiency
      of mitochondrial uncoupling protein 2 (UCP2), which reduces reactive oxygen
      species (ROS) production and functions as upstream to the K-ATP channel in
      determining vulnerability of DA neurons, abolished the protective effects of
      H(2)S against either DA neuron degeneration in the PD mouse model or MPP(+)
      induced injury in primary mesencephalic neurons. Rationally, UCP2 evokes mild
      uncoupling, which in turn diminishes ROS accumulation in DA neurons. Furthermore,
      H(2)S exerted neuroprotective effect via enhancing UCP2-mediated antioxidation
      and subsequently suppressing ROS-triggered endoplasmic reticulum stress as well
      as ultimately inhibiting caspase 12-induced neuronal apoptosis. INNOVATION AND
      CONCLUSION: H(2)S protects DA neurons against degeneration in a UCP2 rather than
      Kir6.2/K-ATP channel-dependent mechanism, which will give us an insight into the
      potential of H(2)S in terms of opening up new therapeutic avenues for PD.

PMID- 22360465
TI  - Miniaturization in biotechnology: speeding up the development of bioprocesses.
AB  - The use of miniaturized devices for fastening bioprocess development, even up to
      production scale, has expanded rapidly, a feature clearly noticeable in recent
      years. This matter was reviewed in a recent past, but several developments have
      occurred since. These will be addressed in the present work, which will provide
      some insight on the use of microfluidic /microstructured reactors and of micro
      scale downstream processing as well, therefore broadening the scope of the
      review.

PMID- 22360464
TI  - Recent progress in the development of anthrax vaccines.
AB  - Bacillus anthracis is the etiological agent of anthrax. Although anthrax is
      primarily an epizootic disease; humans are at risk for contracting anthrax. The
      potential use of B. anthracis spores as biowarfare agent has led to immense
      attention. Prolonged vaccination schedule of current anthrax vaccine and variable
      protection conferred; often leading to failure of therapy. This highlights the
      need for alternative anthrax countermeasures. A number of approaches are being
      investigated to substitute or supplement the existing anthrax vaccines. These
      relied on expression of Protective antigen (PA), the key protective immunogen; in
      bacterial or plant systems; or utilization of attenuated strains of B. anthracis
      for immunization. Few studies have established potential of domain IV of PA for
      immunization. Other targets including the spore, capsule, S-layer and anthrax
      toxin components have been investigated for imparting protective immunity. It has
      been shown that co-immunization of PA with domain I of lethal factor that binds
      PA resulted in higher antibody responses. Of the epitope based vaccines, the loop
      neutralizing determinant, in particular; elicited robust neutralizing antibody
      response and conferred 97% protection upon challenge. DNA vaccination resulted in
      varying degree of protection and seems a promising approach. Additionally, the
      applicability of monoclonal and therapeutic antibodies in the treatment of
      anthrax has also been demonstrated. The recent progress in the direction of
      anthrax prophylaxis has been evaluated in this review.

PMID- 22360466
TI  - The offer of chemistry to targeted therapy in cancer.
AB  - Cancer therapy is facing the big challenge of destroying selectively tumour cells
      without harming the normal tissues. Chemotherapy was trying from the beginning to
      kill malignant cells because of their proliferative activity since normal cells
      are in general quiescent. Meanwhile side effects were produced due to the
      destruction of some normal cells that need regular proliferation. The discovery
      of biomarkers led to the identification of molecular targets within tumour cells
      in order to kill them selectively. Chemistry followed the progress of biomarkers
      biotechnology by the production of target specific antagonists which were the
      subject of many patents. Meanwhile novel problems of tumour resistance appeared
      and made the battle against cancer a non stop development of new strategies and
      new weapons. As a consequence, paralleled activities of patenting biomarkers and
      chemical antagonists are continuously generated. The offer of chemistry does not
      actually limit the efficiency of Targeted therapy but the identification of
      biomarkers is still missing the exclusive specificity to tumour cells.

PMID- 22360467
TI  - Recent achievements on siderophore production and application.
AB  - Iron is the most abundant chemical element on Earth but its most common oxidation
      state is Fe(III) which presents a very low solubility under physiological
      conditions. During evolution, micro-organisms have developed sound strategies to
      acquire iron from both the environment and superior organisms, including direct
      uptake of iron ions from exogenous iron/heme sources and the synthesis of
      specialized Fe(III) chelators called siderophores. The present review paper aims
      at presenting and discussing the latest achievements in siderophore isolation and
      production, as well as novel applications of these molecules in therapies against
      iron-related diseases and in vaccines, and their application as antimicrobial
      agents and biosensors.

PMID- 22360468
TI  - Native and heterologous production of bacteriocins from gram-positive
      microorganisms.
AB  - In nature, microorganisms can present several mechanisms for setting
      intercommunication and defense. One of these mechanisms is related to the
      production of bacteriocins, which are peptides with antimicrobial activity.
      Bacteriocins can be found in Gram-positive and Gram-negative bacteria.
      Nevertheless, bacteriocins produced by Gram-positive bacteria are of particular
      interest due to the industrial use of several strains that belong to this group,
      especially lactic acid bacteria (LAB), which have the status of generally
      recognized as safe (GRAS) microorganisms. In this work, we will review recent
      tendencies in the field of invention and state of art related to bacteriocin
      production by Gram-positive microorganism. Hundred-eight patents related to Gram
      positive bacteriocin producers have been disclosed since 1965, from which 57% are
      related bacteriocins derived from Lactococcus, Lactobacillus, Streptococcus, and
      Pediococcus strains. Surprisingly, patents regarding heterologous bacteriocins
      production were mainly presented just in the last decade. Although the major
      application of bacteriocins is concerned to food industry to control spoilage and
      foodborne bacteria, during the last years bacteriocin applications have been
      displacing to the diagnosis and treatment of cancer, and plant disease resistance
      and growth promotion.

PMID- 22360469
TI  - Recent patents on alphavirus protein expression and vector production.
AB  - Alphaviruses contain a single-strand RNA genome that can be modified to express
      heterologous genes at high levels. Alphavirus vectors can be packaged within
      viral particles (VPs) or used as DNA/RNA layered systems. The broad tropism and
      high expression levels of alphavirus vectors have made them very attractive for
      applications like recombinant protein expression, vaccination or gene therapy.
      Expression mediated by alphavirus vectors is generally transient due to induction
      of apoptosis. However, during the last years several non-cytopathic mutations
      have been identified within the replicase sequence of different alphaviruses,
      allowing prolonged protein expression in culture cells. Some of these mutants,
      which have been patented, have allowed the generation of stable cell lines able
      to express recombinant proteins for extended periods of time in a constitutive or
      inducible manner. Production of alphavirus VPs usually requires cotransfection of
      cells with vector and helper RNAs providing viral structural proteins in trans.
      During this process full-length wild type (wt) genomes can be generated through
      recombination between different RNAs. Several new strategies to reduce wt virus
      generation during packaging, optimize VP production, increase packaging capacity,
      and provide VPs with specific targeting have been recently patented. Finally,
      hybrid vectors between alphavirus and other types of viruses have led to a number
      of patents with applications in vaccination, cancer therapy or retrovirus
      production.

PMID- 22360470
TI  - In vitro propagation of Cichorium intybus L. and quantification of enhanced
      secondary metabolite (esculin).
AB  - In this report, rapid and effective shoot as well as root regeneration system
      through direct multiplication was successfully developed for Cichorium intybus L.
      Furthermore, the effect of exogenous growth regulators (TDZ and IAA) at different
      concentrations on the regulation process of the plant was also studied. Enhanced
      production of esculin in developed C. intybus L. was evaluated using leaf
      extract. Only on the expense of 20 days, regeneration was seen and very low dose
      of TDZ was seen to be more effective. When 0.02 mg/L of TDZ was combined with
      1.5mg/L of IAA, nearly 100% of explants produced shoots with the highest number
      of regenerated shoots (85.37). With further increase in concentration (>= 0.05
      mg/L), the number of shoots per explants get decreased. A lower NAA to IBA ratio
      (1.0mg/L of IBA and 0.5mg/L of NAA) seemed to be more effective for root
      generation and considered to be the most effective combination among the tried
      groups. IBA was more effective in root development than NAA, but both were
      comparatively effective. On quantitative analysis by RP-HPLC, the 76.23% of
      Esculin were found in leaf extract of the in vitro developed C. intybus L. This
      amount was 26.77% higher than normal grown plants.

PMID- 22360471
TI  - Can strict volume control be the key for treatment and prevention of posterior
      reversible encephalopathy syndrome in hemodialysis patients?
AB  - Posterior reversible encephalopathy syndrome (PRES) is a rare but if diagnosed
      late an irreversible disease. The majority of the patients present with severe
      hypertension, and effective blood pressure control is the mainstay of therapy. In
      this case report, we present three cases with PRES, treated successfully with
      strict volume control policy and propose that strict volume control policy may be
      a key element for the treatment of PRES.

PMID- 22360472
TI  - Geographical patterns of parasite infracommunities in the rough scad, Trachurus
      lathami Nichols, in the Southwestern Atlantic ocean.
AB  - We assessed temporal variability in parasite infections of rough scad (Trachurus
      lathami) in 3 samples from Miramar (MI) in 2008, separated by periods of 1 mo,
      and 2 samples from Villa Gesell (VG), 1 each in 2008 and 2009 (Buenos Aires
      Province, Argentina), respectively. A sample was also obtained from Cabo Frio
      (CF) (Brazil) in 2009 to compare differences in parasite communities between fish
      from this locality and each Argentinean locality. All rough scad were parasitized
      by at least 1 of 27 parasite species. Similarity-based multivariate analysis
      revealed significant differences between localities, but temporal homogeneity in
      each Argentinean locality. Overall, prevalence and abundance of parasite species
      were most similar between samples from MI and VG, while the greatest differences
      occurred between samples from MI and CF. A canonical analysis of principal
      coordinates showed significant differences among samples. Grillotia
      carvajalregorum was the most important species in determining the position of
      Argentinean samples, especially those from MI, while Ectenurus virgulus ,
      Raphidascaris sp., and Hysterothylacium sp. were the most important species
      related to fish from CF. The parasite assemblage of T. lathami showed a notable
      temporal persistence within the same locality and a high variability at the
      spatial scale, suggesting the existence of 3 independent stocks of T. lathami in
      South Atlantic waters.

PMID- 22360474
TI  - Minimally invasive heminephrectomy: feasibility and outcomes.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) has become a well
      established treatment for patients with selected renal malignancies. As the
      skills of urologic laparoscopic surgeons have increased, more complex and larger
      tumors are now being approached in this manner. Laparoscopic heminephrectomy
      (LHN), defined as the resection of >30% of a kidney, is described in this
      article. Standardized nephrometry scoring is used to grade tumor complexity;
      complications, renal function, and perioperative outcomes are discussed. PATIENTS
      AND METHODS: One hundred forty-five patients underwent minimally invasive partial
      nephrectomy. Parameters studied included patient demographics, tumor
      characteristics, operative time, estimated blood loss (EBL), length of stay
      (LOS), clamp time, change in renal function over time, and complication rate
      using the Clavien system. RESULTS: Twenty-four patients underwent LHN. Patients
      who had LHN performed had significantly larger tumors (4.7 vs 2.6 cm, P=0.05)
      with higher nephrometry scoring (6.6 vs 5.0, P=0.007). On univariate analysis,
      both operative (176.0 vs 151.6 min, P=0.036) and clamp time (29.3 vs 21.9 min,
      P=0.003) were significantly increased. There was no difference in LOS, EBL,
      change of renal function over time, or complications. CONCLUSIONS: LHN is
      efficacious and feasible. Although both operative and clamp times were
      significantly increased, there was no significant impact on LOS, EBL, change in
      renal function over time, or complication rate.

PMID- 22360473
TI  - Reactivators of acetylcholinesterase inhibited by organophosphorus nerve agents.
AB  - Since the September 11, 2001, terrorist attacks in the United States, the specter
      of a chemical threat against civilian populations has renewed research interest
      in chemical warfare agents, their mechanisms of action, and treatments that
      reverse their effects. In this Account, we focus specifically on organophosphorus
      nerve agents (OPNAs). Although some OPNAs are used as pest control, the most
      toxic chemicals in this class are used as chemical warfare agents in armed
      conflicts. The acute toxicity of OPNAs results from the irreversible inhibition
      of acetylcholinesterase (AChE, EC 3.1.1.7) via the formation of a covalent P-O
      bond at the serine hydroxyl group in the enzyme active site. AChE breaks down the
      neurotransmitter acetylcholine at neuronal synapses and neuromuscular junctions.
      The irreversible inhibition of AChE causes the neurotransmitter to accumulate in
      the synaptic cleft, leading to overstimulation of cholinergic receptors,
      seizures, respiratory arrest, and death.  The current treatment for OPNA
      poisoning combines an antimuscarinic drug (e.g., atropine), an anticonvulsant
      drug (e.g., diazepam), and an AChE reactivator of the pyridinium aldoxime family
      (pralidoxime, trimedoxime, obidoxime, HI-6, HLo-7). Because of their high
      nucleophilicity, oximes can displace the phosphyl group from the catalytic
      serine, thus restoring the enzyme's catalytic activity. During 50 years of
      research in the reactivator field, researchers have synthesized and tested
      numerous structural modifications of monopyridinium oximes and bispyridinium
      oximes. In the past decade, medicinal chemists have focused their research on the
      more efficient bispyridinium reactivators, but all known reactivators have
      several drawbacks. First, due to their permanent positive charge, they do not
      cross the blood-brain barrier (BBB) efficiently and do not readily reactivate
      AChE in the central nervous system. Second, no single oxime is efficient against
      a wide variety of OPNAs. Third, oximes cannot reactivate "aged" AChE.  This
      Account summarizes recent strategies for the development of AChE reactivators
      capable of crossing the BBB. The use of nanoparticulate transport and inhibition
      of P-glycoprotein efflux pumps improves BBB transport of these AChE reactivators.
      Chemical modifications that increased the lipophilicity of the pyridinium
      aldoximes, the addition of a fluorine atom and the replacement of a pyridyl ring
      with a dihydropyridyl moiety, enhances BBB permeability. The glycosylation of
      pyridine aldoximes facilitates increased BBB penetration via the GLUT-1 transport
      system. The development of novel uncharged reactivators that can move efficiently
      across the BBB represents one of the most promising of these new strategies.

PMID- 22360475
TI  - The global role of kidney transplantation.

PMID- 22360476
TI  - Rhabdomyolysis after a regular exercise session in a patient with Graves'
      disease.

PMID- 22360477
TI  - Aliskiren for reninoma.

PMID- 22360478
TI  - Editorial: pharmacotherapeutic implications of host-pathogen interactions:
      emerging concepts.
AB  - Although the parasitology belongs to one of the longest established disciplines,
      the recent methodical advances led to the substantial broadening of the
      possibilities for the detection and treatment of parasitic diseases. However, the
      exact mechanisms involved in the parasite establishment and survival are
      frequently unclear and only recently uncovered. At the cellular level, the
      emerging mechanisms, discussed in this journal issue, include the newly
      recognized role of mast cells in the host defense against bacterial pathogens,
      and the role of granulocytes in the host defense against helminths. At the
      protein level, we discuss here the emerging role of protein tyrosine phosphatases
      as both targets and tools of nonmetazoan pathogens and viruses. At the level of
      small signaling molecules, we attempt here to highlight the role of reactive
      oxygen species as molecules involved both in the host defense, but also produced
      by some human pathogens and commensals. Scientometric analysis of the fields
      covered by this journal issue is provided.

PMID- 22360480
TI  - Mast cells as critical effectors of host immune defense against Gram-negative
      bacteria.
AB  - Mast cells are best known as central effector cells in IgE-mediated type I
      allergic diseases including asthma and hay fever. An increasing amount of
      evidence, however, has demonstrated that mast cells are sentinel cells playing a
      critical role in host defense against invading microbes. Mast cells are located
      immediately beneath the epithelial surfaces exposed to the outer environment,
      such as genitourinary and gastrointestinal tracts, skin, and airways. This review
      discusses recent studies on the critical roles of mast cells in host defense
      against Gram-negative bacterial infection. Mast cells are equipped with multiple
      receptors detecting the invading Gram-negative bacteria in both direct (opsonin
      independent) and indirect (opsonin-dependent) mechanisms. The former includes
      Toll-like receptors (TLRs), CD48, and nucleotide-binding oligomerization (NOD)
      proteins, while the latter includes Fcgamma receptors (FcgammaRs) and complement
      receptors. In addition to the detecting systems, mast cells are also armed with
      versatile tools to combat and kill Gram-negative bacteria. In response to the
      recognition of the Gram-negative bacterial infection, mast cells secrete various
      types of mediators which either regulate host immune system or directly attack
      the bacteria. Mast cells can also phagocytize and subsequently display the
      bacterial antigens on their cell surfaces. Moreover, recent findings have
      revealed the formation of extra-cellular traps by mast cells. Finally this review
      will especially focus on recent findings on LPS signaling in mast cells, both the
      functional outcome and the molecular mechanisms.

PMID- 22360481
TI  - Leishmaniasis: prevention, parasite detection and treatment.
AB  - Leishmaniasis remains a public health problem worldwide, affecting approximately
      12 million people in 88 countries; 50 000 die of it each year. The disease is
      caused by Leishmania, obligate intracellular vector-borne parasites. In spite of
      its huge health impact on the populations in vast areas, leishmaniasis is one of
      the most neglected diseases. No safe and effective vaccine currently exists
      against any form of human leishmaniasis. The spectrum and efficacy of available
      antileishmanial drugs are also limited. First part of this review discusses the
      approaches used for the vaccination against leishmaniasis that are based on the
      pathogen and includes virulent or attenuated parasites, parasites of related
      nonpathogenic species, whole killed parasites, parasites' subunits, DNA vaccines,
      and vaccines based on the saliva or saliva components of transmitting
      phlebotomine vector. Second part describes parasite detection and quantification
      using microscopy assays, cell cultures, immunodetection, and DNA-based methods,
      and shows a progress in the development and application of these techniques. In
      the third part, first-line and alternative drugs used to treat leishmaniasis are
      characterized, and pre-clinical research of a range of natural and synthetic
      compounds studied for the leishmanicidal activity is described. The review also
      suggests that the application of novel strategies based on advances in genetics,
      genomics, advanced delivery systems, and high throughput screenings for
      leishmanicidal compounds would lead to improvement of prevention and treatment of
      this disease.

PMID- 22360479
TI  - Inflammatory responses to respiratory syncytial virus (RSV) infection and the
      development of immunomodulatory pharmacotherapeutics.
AB  - Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a
      major respiratory pathogen of infants and children and an emerging pathogen of
      the elderly. Current management of RSV disease includes monoclonal antibody
      prophylaxis for infants identified as high risk and supportive care for those
      with active infection; there is no vaccine, although several are under study. In
      this manuscript, we review published findings from human autopsy studies, as well
      as experiments that focus on human clinical samples and mouse models of acute
      pneumovirus infection that elucidate basic principles of disease pathogenesis.
      Consideration of these data suggests that the inflammatory responses to RSV and
      related pneumoviral pathogens can be strong, persistent, and beyond the control
      of conventional antiviral and anti-inflammatory therapies, and can have profound
      negative consequences to the host. From this perspective, we consider the case
      for specific immunomodulatory strategies that may have the potential to alleviate
      some of the more serious sequelae of this disease.

PMID- 22360482
TI  - Redox regulation in malaria: current concepts and pharmacotherapeutic
      implications.
AB  - Malaria imposes a serious threat to human and becomes more prevalent due to the
      emergence of drug resistant parasite. Understanding of the underlying mechanism
      of drug resistance and identification of novel drug targets are key effective
      processes for the management of malaria. Malaria parasite is highly susceptible
      to oxidative stress but lives in a pro-oxidant rich environment containing oxygen
      and iron, which produce a large amount of reactive oxygen species. Management of
      oxidative stress in malaria parasite is tightly regulated through active redox
      and antioxidant defense systems. The elevation of oxidative stress as a result of
      inhibition of any component of this defense system leads to redox imbalance and
      ultimately parasite death. Therefore, redox system plays an indispensable role
      for the survival of parasite within the host. Identification of key molecules,
      which disrupt parasite redox balance by altering key redox reactions and promote
      oxidative stress in parasites, would be an effective approach to develop novel
      antimalarial drugs. During the last few decades, contributions by researchers
      around the globe provide even better understanding of redox biology of malaria
      parasite. Here, in this review, we are highlighting the knowledge gathered so far
      regarding the essential redox-active processes and their components in malaria
      parasite to overcome elevated oxidative insults. We have also given maximum
      efforts to enlist currently used redox-active antimalarials, their mode of action
      and pharmacotherapeutic implications.

PMID- 22360485
TI  - Finding the smoking gun: protein tyrosine phosphatases as tools and targets of
      unicellular microorganisms and viruses.
AB  - Protein tyrosine phosphatases (PTPs) are increasingly recognized as important
      effectors of host-pathogen interactions. Since Guan and Dixon reported in 1990
      that phosphatase YopH serves as an essential virulence determinant of Yersinia,
      the field shifted significantly forward, and dozens of PTPs were identified in
      various microorganisms and even in viruses. The discovery of extensive tyrosine
      signaling networks in non-metazoan organisms refuted the moth-eaten paradigm
      claiming that these organisms rely exclusively on phosphoserine/phosphothreonine
      signaling. Similarly to humans, phosphotyrosine signaling is thought to comprise
      a small fraction of total protein phosphorylation, but plays a disproportionately
      important role in cell-cycle control, differentiation, and invasiveness. Here we
      summarize the state-of-art knowledge on PTPs of important non-metazoan pathogens
      (Listeria monocytogenes, Staphylococcus aureus, Porphyromonas gingivalis,
      Caulobacter crescentus, Yersinia, Synechocystis, Leishmania, Plasmodium
      falciparum, Entamoeba histolytica, etc.), and focus also at the microbial
      proteins affecting directly or indirectly the PTPs of the host (Mycobacterium
      tuberculosis MTSA-10, Bacillus anthracis anthrax toxin, streptococcal beta
      protein, Helicobacter pylori CagA and VacA, Leishmania GP63 and EF-1alpha,
      Plasmodium hemozoin, etc.). This is the first review summarizing the knowledge on
      biological activity and pharmacological inhibition of non-metazoan PTPs, with the
      emphasis of those important in host-pathogen interactions. Targeting of numerous
      non-metazoan PTPs is simplified by the fact that they act either as
      ectophosphatases or are secreted outside of the pathogen. Interfering with
      tyrosine phosphorylation represents a powerful pharmacologic approach, and even
      though the PTP inhibitors are difficult to develop, lifting the fog of
      phosphatase inhibition is of the great market potential and further clinical
      impact.

PMID- 22360483
TI  - Current advances in detection and treatment of babesiosis.
AB  - Babesiosis is a disease with a world-wide distribution affecting many species of
      mammals principally cattle and man. The major impact occurs in the cattle
      industry where bovine babesiosis has had a huge economic effect due to loss of
      meat and beef production of infected animals and death. Nowadays to those costs
      there must be added the high cost of tick control, disease detection, prevention
      and treatment. In almost a century and a quarter since the first report of the
      disease, the truth is: there is no a safe and efficient vaccine available, there
      are limited chemotherapeutic choices and few low-cost, reliable and fast
      detection methods. Detection and treatment of babesiosis are important tools to
      control babesiosis. Microscopy detection methods are still the cheapest and
      fastest methods used to identify Babesia parasites although their sensitivity and
      specificity are limited. Newer immunological methods are being developed and they
      offer faster, more sensitive and more specific options to conventional methods,
      although the direct immunological diagnoses of parasite antigens in host tissues
      are still missing. Detection methods based on nucleic acid identification and
      their amplification are the most sensitive and reliable techniques available
      today; importantly, most of those methodologies were developed before the
      genomics and bioinformatics era, which leaves ample room for optimization. For
      years, babesiosis treatment has been based on the use of very few drugs like
      imidocarb or diminazene aceturate. Recently, several pharmacological compounds
      were developed and evaluated, offering new options to control the disease. With
      the complete sequence of the Babesia bovis genome and the B. bigemina genome
      project in progress, the post-genomic era brings a new light on the development
      of diagnosis methods and new chemotherapy targets. In this review, we will
      present the current advances in detection and treatment of babesiosis in cattle
      and other animals, with additional reference to several apicomplexan parasites.

PMID- 22360484
TI  - Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic
      implications.
AB  - The resident prokaryotic microbiota of the mammalian intestine influences diverse
      homeostatic functions, including regulation of cellular growth, maintenance of
      barrier function, and modulation of immune responses. However, it is unknown how
      commensal prokaryotic organisms mechanistically influence eukaryotic signaling
      networks. Recent data has demonstrated that gut epithelia contacted by enteric
      commensal bacteria rapidly generate reactive oxygen species (ROS). While the
      induced generation of ROS via stimulation of formyl peptide receptors is a
      cardinal feature of the cellular response of phagocytes to pathogenic or
      commensal bacteria, evidence is accumulating that ROS are also similarly elicited
      in other cell types, including intestinal epithelia, in response to microbial
      signals. Additionally, ROS have been shown to serve as critical second messengers
      in multiple signal transduction pathways stimulated by proinflammatory cytokines
      and growth factors. This physiologically-generated ROS is known to participate in
      cellular signaling via the rapid and transient oxidative inactivation of a
      defined class of sensor proteins bearing oxidant-sensitive thiol groups. These
      proteins include tyrosine phosphatases that serve as regulators of MAP kinase
      pathways, cytoskeletal dynamics, as well as components involved in control of
      ubiquitination-mediated NF-kappaB activation. Consistently, microbial-elicited
      ROS has been shown to mediate increased cellular proliferation and motility and
      to modulate innate immune signaling. These results demonstrate how enteric
      microbiota influence regulatory networks of the mammalian intestinal epithelia.
      We hypothesize that many of the known effects of the normal microbiota on
      intestinal physiology, and potential beneficial effects of candidate probiotic
      bacteria, may be at least partially mediated by this ROS-dependent mechanism.

PMID- 22360487
TI  - Non-alcoholic steatohepatitis: what can we learn from animal models?
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of
      abnormal liver function and correlates with central adiposity, obesity, insulin
      resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological
      spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis
      (NASH), advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. Though
      NAFLD and NASH are becoming a major public health problem, ethical constraints on
      obtaining human liver tissue limit the interpretability of the data and the
      ability to delineate cause and effect from complex, interactive disease
      pathogenic pathways. Animal models of NASH can provide critical information
      leading to identify potential drug targets and to understand their molecular
      mechanisms, and are platforms for compound screening in drug development and for
      the assessment of novel therapeutic strategies. This review is aimed to offer an
      updated overview of the nutritional, genetic and pharmacologic animal models of
      NASH. Though the information derived from these models has clear relevance for
      the comprehension of the molecular basis of human disease, most of them fail to
      reproduce the full spectrum of liver pathology and the metabolic context that
      characterizes human NASH. Consequently, it is necessary to establish animal
      models that can best mimic the actual etiology, progression, and pathogenesis of
      the disease, and prove effectiveness for examining and selecting compounds with
      potential therapeutic benefit in NASH.

PMID- 22360488
TI  - Update on the slow delayed rectifier potassium current (I(Ks)): role in
      modulating cardiac function.
AB  - The slow delayed rectifier current (I(Ks)) is the slow component of cardiac
      delayed rectifier current and is critical for the late phase repolarization of
      cardiac action potential. This current is also an important target for
      Sympathetic Nervous System (SNS) to regulate the cardiac electivity to
      accommodate to heart rate alterations in response to exercise or emotional stress
      and can be up-regulated by beta- adrenergic or other signal molecules. I(Ks)
      channel is originated by the co-assembly of pore-forming KCNQ1 alpha-subunit and
      accessory KCNE1 beta-subunit. Mutations in any subunit can bring about severe
      long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and
      sudden death. This review summarizes the normal physiological functions and
      molecular basis of I(Ks) channels, as well as illustrates up-to-date development
      on its blockers and activators. Therefore, the current extensive survey should
      generate fundamental understanding of the role of I(Ks) channel in modulating
      cardiac function and donate some instructions to the progression of I(Ks)
      blockers and activators as potential antiarrhythmic agents or pharmacological
      tools to determine the physiological and pathological function of I(Ks).

PMID- 22360489
TI  - Stability of gold nanorods passivated with amphiphilic ligands.
AB  - The stability of gold nanorods (NRs) coated with amphiphilic ligands (ALs) was
      investigated. NRs coated with cetyltrimethylammonium bromide (CTAB) were ligand
      exchanged with polyoxyethylene [10] cetyl ether (Brij56), Oligofectamine (OF),
      and phosphatidylserine (PS). An aggregation index based on the longitudinal
      surface plasmon resonance peak broadening was used to measure stability of the NR
      ALs under different conditions including the number of washes, pH, ionic
      concentration, and temperature. The aggregation index was also used to measure
      the stability of the NR-ALs under ultrafast laser irradiation and in the presence
      of proteins commonly used in cell culture. Differences in NR-AL stability were
      found, which were due to differences in the physical and chemical properties of
      the ALs. Apart from the charge on the AL headgroup, we suggest the Gibbs free
      energy of passivation (DeltaG(p)) and enthalpy of passivation (DeltaH(p)) of the
      AL could potentially aid in the selection of amphiphiles that can effectively
      passivate NRs for stability and optimize their properties and desired biological
      impact.

PMID- 22360490
TI  - Production of human lactoferrin in animal milk.
AB  - Genetic constructs containing the human lactoferrin (hLf) gene were created
      within a joint program of Russian and Belorussian scientists. Using these
      constructs, transgenic mice were bred (the maximum hLf concentration in their
      milk was 160 g/L), and transgenic goats were also generated (up to 10 g/L hLf in
      their milk). Experimental goatherds that produced hLf in their milk were also
      bred, and the recombinant hLf was found to be identical to the natural protein in
      its physical and chemical properties. These properties included electrophoretic
      mobility, isoelectric point, recognition by polyclonal and monoclonal antibodies,
      circular dichroic spectra, interaction with natural ligands (DNA,
      lipopolysaccharides, and heparin), the binding of iron ions, the sequence of the
      7 terminal amino acids, and its biological activity. The latter was assessed by
      the agglutination of Micrococcus luteus protoplasts, bactericidal activity
      against Escherichia coli and Listeria monocytogenes , and fungicidal activity
      against Candida albicans . We also demonstrated a significant increase in the
      activity of antibiotics when used in combination with Lf.

PMID- 22360491
TI  - CMC-modified cellulose biointerface for antibody conjugation.
AB  - In this Article, we present a new strategy for preparing an antihemoglobin
      biointerface on cellulose. The preparation method is based on functionalization
      of the cellulose surface by the irreversible adsorption of CMC, followed by
      covalent linking of antibodies to CMC. This would provide the means for
      affordable and stable cellulose-based biointerfaces for immunoassays. The
      preparation and characterization of the biointerface were studied on Langmuir
      Schaefer cellulose model surfaces in real time using the quartz crystal
      microbalance with dissipation and surface plasmon resonance techniques. The
      stable attachment of antihemoglobin to adsorbed CMC was achieved, and a linear
      calibration of hemoglobin was obtained. CMC modification was also observed to
      prevent nonspecific protein adsorption. The antihemoglobin-CMC surface
      regenerated well, enabling repeated immunodetection cycles of hemoglobin on the
      same surface.

PMID- 22360492
TI  - Host sensitization of Tb3+ ions in tribarium lanthanide borates Ba3Ln (BO3)3 (Ln
      = Lu and Gd).
AB  - The vacuum-ultraviolet (VUV) spectroscopic properties of undoped and Tb(3+)-doped
      borates Ba(3)Ln(BO(3))(3) (Ln = Lu and Gd) with different crystal structures were
      investigated by using synchrotron radiation. Ba(3)Lu(BO(3))(3) (BLB) crystallizes
      in a hexagonal structure, whereas Ba(3)Gd(BO(3))(3) (BGB) crystallizes in a
      trigonal structure. The maximum host absorption for BLB and BGB was found to
      locate at ~179 and ~195 nm, respectively. Upon host excitation, BLB exhibits an
      intrinsic broad UV emission centered at 339 nm, which is attributed to the
      recombination of self-trapped excitons that may presumably be associated with
      band-gap excitations or molecular transitions within the BO(3)(3-) group. In
      contrast to BLB, no broad emission but line emission ascribed to a Gd(3+)(6)P(J)
      (8)S(7/2) transition was observed in the emission spectrum of BGB. Upon doping of
      Tb(3+) ions into the hosts of BLB and BGB, an efficient energy transfer from the
      host excitations to Tb(3+) via host/Gd(3+) emission was observed, showing that
      host sensitization of Tb(3+) occurs in these rare-earth borates.

PMID- 22360493
TI  - Benefits of active participation of family physicians in geriatric consultations.
AB  - BACKGROUND: Geriatric consultation services are generally beneficial in improving
      the health and well-being of the elderly. We prospectively studied whether the
      active participation of family physicians (FPs) in the process of geriatric
      consultation would improve implementation rates and benefit the health care of
      the elderly. METHODS: We carried out a comparative prospective intervention study
      in three urban academic family medicine clinics. Patients in the control clinics
      were evaluated by the consultant geriatrician, and a summary of the findings and
      recommendations were presented to the FP in a brief meeting. In the intervention
      clinic, the referring FP joined the geriatrician throughout the geriatric
      assessment. The percentage of implementation of suggested recommendations was
      evaluated. Information regarding the utilization of health services was provided
      from computerized data. RESULTS: Of the 212 patients included in the study, 107
      were in the intervention group and 105 were controls. The overall rate of
      implementation was significantly higher for patients in the intervention group
      (329/445; 73.9%) than for patients in the control group (232/387; 59.9%), P <
      0.0001. In the year after the geriatric assessment, those in the intervention
      group visited the FP less often. CONCLUSIONS: A model co-consultation actively
      involving the FP in the process of assessment of the older patient by the
      geriatrician improves the degree of implementation of recommendations without an
      increase in related heath care utilization and costs. This model should be
      further developed and studied.

PMID- 22360486
TI  - Granulocytes in helminth infection -- who is calling the shots?
AB  - Helminths are parasitic organisms that can be broadly described as "worms" due to
      their elongated body plan, but which otherwise differ in shape, development,
      migratory routes and the predilection site of the adults and larvae. They are
      divided into three major groups: trematodes (flukes), which are leaf-shaped,
      hermaphroditic (except for blood flukes) flatworms with oral and ventral suckers;
      cestodes (tapeworms), which are segmented, hermaphroditic flatworms that inhabit
      the intestinal lumen; and nematodes (roundworms), which are dioecious,
      cylindrical parasites that inhabit intestinal and peripheral tissue sites.
      Helminths exhibit a sublime co-evolution with the host's immune system that has
      enabled them to successfully colonize almost all multicellular species present in
      every geographical environment, including over two billion humans. In the face of
      this challenge, the host immune system has evolved to strike a delicate balance
      between attempts to neutralize the infectious assault versus limitation of damage
      to host tissues. Among the most important cell types during helminthic invasion
      are granulocytes: eosinophils, neutrophils and basophils. Depending on the
      specific context, these leukocytes may have pivotal roles in host protection,
      immunopathology, or facilitation of helminth establishment. This review provides
      an overview of the function of granulocytes in helminthic infections.

PMID- 22360494
TI  - Parsing the components of the psychomotor syndrome in schizophrenia.
AB  - OBJECTIVE: Catatonia, extrapyramidal signs, psychomotor slowing, and (motoric)
      neurological soft signs are well-known psychomotor symptoms in schizophrenia.
      This study aims at investigating the interrelations between these symptoms. In
      addition, associations between psychomotor symptoms, clinical symptoms, and
      cognitive functioning will be studied. METHOD: An extensive test battery
      containing psychomotor (Bush Francis Catatonia Rating Scale; St Hans Rating
      Scale; Salpetriere Retardation Rating Scale; Neurological Evaluation Scale) and
      clinical (Positive and Negative Syndrome Scale; Calgary Depression Scale) rating
      scales as well as instrumental psychomotor tests (Line Copying Task; Finger
      Tapping Task) and cognitive tasks (Symbol Digit Substitution Test; Stroop Colour
      Word Test; Continuous Performance Test; Letter Number Sequencing) was
      administered to a sample of 124 patients with schizophrenia or schizoaffective
      disorder. RESULTS: Correlational analyses showed that two clusters emerge from
      our data: first, a psychomotor poverty cluster referring to the interrelations
      between catatonia, parkinsonism, psychomotor slowing, and negative symptoms;
      second, a cluster containing motoric neurological soft signs, which were found to
      be correlated with cognitive functioning. CONCLUSION: Psychomotor abnormalities
      are highly prevalent phenomena in schizophrenia that have to be considered as a
      heterogeneous construct. However, longitudinal and neurobiological research is
      needed to further explore the precise nature of the interrelations found in this
      study.

PMID- 22360495
TI  - Impact of the 2005 smoke-free policy in Italy on prevalence, cessation and
      intensity of smoking in the overall population and by educational group.
AB  - AIMS: To estimate the immediate as well as the longer-term impact of the 2005
      smoke-free law on smoking prevalence, cessation and intensity both in the overall
      population and separately by educational level. DESIGN: Interrupted time-series
      analyses of 11 cross-sectional nationally representative surveys. SETTING: Italy,
      1999-2010. PARTICIPANTS: Adults aged 20-64 years. MEASUREMENTS: For each year we
      computed the prevalence of current smoking, the quit ratio and the mean number of
      cigarettes smoked per day. All measures were standardized by age. Segmented
      linear regression analyses were performed for each smoking variable separately by
      sex. FINDINGS: Among males, smoking prevalence decreased by 2.6% (P = 0.002) and
      smoking cessation increased by 3.3% (P = 0.006) shortly after the ban, but both
      measures tended to return to pre-ban values in the following years. This occurred
      among both highly and low-educated males. Among low-educated females, the ban was
      followed by a 1.6% decrease (P = 0.120) in smoking prevalence and a 4.5% increase
      in quit ratios (P < 0.001). However, these favourable trends reversed over the
      following years. Among highly educated females, trends in smoking prevalence and
      cessation were not altered by the ban. Among both males and females, long-term
      trends in the daily number of cigarettes, which were already declining well
      before the implementation of the policy, changed to a minor extent. CONCLUSION:
      The impact of the Italian smoke-free policy on smoking and inequalities in
      smoking was short-term. Smoke-free policies may not achieve the secondary effect
      of reducing smoking prevalence in the long term, and they may have limited
      effects on inequalities in smoking.

PMID- 22360496
TI  - Contesting conventional periodontal wisdom: implications for periodontal
      classifications.
AB  - This paper examines the common approach used to classify periodontal diseases and
      how this obstructs our understanding of the disease process. We address the
      implications of including etiological and pathogenesis-related considerations in
      the classifications of complex diseases like periodontitis and argue that the
      number of periodontal entities in a classification system ought to be determined
      by well-documented differences in the management of each entity. We finally
      discuss how an ecosocial theory of disease distribution can be helpful to
      understand the determinants of the distribution of disease in the population.

PMID- 22360497
TI  - Wnt/beta-catenin signaling participates in cementoblast/osteoblast
      differentiation of dental follicle cells.
AB  - Dental follicle cells (DFCs) are reported to contain stem cells. The canonical
      Wnt signaling pathway plays an important role in stem cell self-renewal and tooth
      development through beta-catenin expression. The objective of this study was to
      investigate whether Wnt/beta-catenin signaling pathway participates in the
      cementoblast/osteoblast differentiation of rat DFCs. Immunohistochemistry was
      used to compare the expression of beta-catenin in rat mandibular first molars
      from postnatal days 1-13. The effects of Wnt/beta-catenin signaling on DFCs in
      vitro were examined by lithium chloride (LiCl) treatment by immunofluorescence,
      cell counting, dual-luciferase reporter assays, western blotting, and alkaline
      phosphatase activity analysis. beta-Catenin expression was absent in the dental
      follicles on days 1 and 3 in vivo. It then progressively increased from days 5 to
      13. In vitro studies of the DFCs showed that LiCl stimulation caused beta
      catenin, which was mainly located in the cell membrane and cytoplasm of DFCs, to
      be immediately transferred to the nucleus and led to the inhibition of
      proliferation at 12 and 24 hr. LiCl treatment also downregulated the levels of
      phosphorylated-beta-catenin, while upregulating the levels of total beta-catenin,
      nuclear beta-catenin, osteocalcin, runt-related transcription factor 2, and
      collagen type I. In addition, LiCl enhanced the beta-catenin/T-cell factor
      luciferase activity and alkaline phosphatase activity. These results suggest that
      Wnt/beta-catenin signaling pathway positively regulates the
      cementoblast/osteoblast differentiation of the DFCs.

PMID- 22360498
TI  - Lipase-catalyzed incorporation of different Fatty acids into tripalmitin-enriched
      triacylglycerols: effect of reaction parameters.
AB  - Tripalmitin-enriched triacylglycerols were concentrated from palm stearin by
      acetone fractionation and as the substrate reacted with a mixture of equimolar
      quantities of fatty acids (C8:0-C18:3). The incorporation degree and acyl
      migration level of the fatty acids and acylglycerols composition were
      investigated, providing helpful information for the production of human milk fat
      substitutes. Higher incorporation degrees of the fatty acids were obtained with
      lipase PS IM, Lipozyme TL IM, and Lipozyme RM IM followed by porcine pancreatic
      lipase and Novozym 435-catalyzed acidolysis. During reactions catalyzed by
      Lipozyme TL IM, Lipozyme RM IM, and lipase PS IM, incorporation degrees of C12:0,
      C14:0, C18:1, and C18:2 were higher than those of other fatty acids at operated
      variables (molar ratio, temperature, and time), and the triacylglycerols content
      reached the highest (82.09%) via Lipozyme RM IM-catalyzed acidolysis. On the
      basis of significantly different levels of acyl migration to the sn-2 position,
      lipases were in the order of lipase PS IM < Lipozyme TL IM < Lipozyme RM IM.

PMID- 22360499
TI  - Engineering the interface between glucose oxidase and nanoparticles.
AB  - The behavior of glucose oxidase (GOx) on gold nanoparticles (NPs) was
      investigated as a function of (1) NP surface chemistry, (2) stabilizing protein
      additives, and (3) protein microenvironment. GOx secondary structure and
      unfolding was probed by circular dichroism (CD) spectroscopy and fluorescence,
      and GOx enzymatic activity was measured by a colorimetric assay. We also examined
      the activity and structure of GOx after displacement from the NP surface.
      Generally, GOx behavior was negatively impacted by conjugation to the NP, and
      conjugation conditions could vary the influence of the NP. Surface chemistry and
      protein microenvironment could improve behavior, but addition of stabilizing
      proteins negatively influenced activity. After displacement from the NPs, GOx
      tended to remain unfolded, indicating that the interactions with the NP were
      irreversible.

PMID- 22360500
TI  - Comparison of the palindrome vs. step-tip tunneled hemodialysis catheter: a
      prospective randomized trial.
AB  - Numerous designs for tunneled hemodialysis catheter have been developed in an
      effort to improve catheter function and survival. In this prospective randomized
      controlled study, 97 patients were randomized into the palindrome catheter group
      (PC, n = 47) and step-tip catheter group (SC, n = 50). Demographic
      characteristics were not different between the two groups. The effective blood
      flow rates at different pump speeds were comparable between the two groups. The
      recirculation was low within acceptable range in both types of catheter, and
      hemodialysis adequacy was not different between the two groups. However, when
      arterial and venous blood lines were reversed, while the recirculation was
      significantly increased in SC, it was not increased at all in PC. The catheter
      dysfunction-free survival rate was significantly higher in PC than in SC (78.9%
      vs. 54.4% at 2 months, p = 0.008). The overall catheter survival rate was also
      higher in PC than in SC (90.6% vs. 68.8% at 2 months, p = 0.015). We conclude
      that both catheters are equally effective on the adequate hemodialysis and low
      recirculation. However, the PCs have advantages over the SCs in terms of lower
      catheter dysfunction rate, lower recirculation with reversed blood lines, higher
      short-term catheter survival rate.

PMID- 22360501
TI  - Phenothiazinyl rhodanylidene merocyanines for dye-sensitized solar cells.
AB  - Phenothiazinyl rhodanylidene acetic acid merocyanine dyes with variable
      substitution pattern on the peripheral benzene ring were synthesized in good to
      excellent yields by Knoevenagel condensation of the corresponding phenothiazinyl
      aldehydes and rhodanine-N-acetic acid. The electronic properties were
      investigated by cyclic voltammetry, absorption, and fluorescence spectroscopy.
      Electron releasing substitution leads to an appreciable lowering of the oxidation
      potential, bathochromic shift of the absorption band, and minimization of the
      emission quantum yield. Not least as a consequence of these properties, the
      compounds are interesting for use as chromophores in dye-sensitized solar cells
      (DSSC). DSSCs were constructed and successfully tested by determining the
      characteristic parameters such as incident-photon-to-electron conversion
      efficiency (IPCE), fill factor (FF), and overall efficiency.

PMID- 22360502
TI  - Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer.
AB  - Papillary thyroid carcinoma (PTC) has long been diagnosed based on its unique
      nuclear features (PTC-N); however, significant observer discrepancies have been
      reported in the diagnosis of encapsulated follicular patterned lesions (EnFPLs),
      because the threshold of PTC-N is subjective. An equivocal PTC-N may often occur
      in non-invasive EnFPLs and benign/malignant disagreements often create serious
      problems for patients' treatment. This review collects recent publications
      focusing on the so-called encapsulated follicular variant of papillary thyroid
      carcinoma (EnFVPTC) and tries to emphasize problems in the histopathological
      diagnosis of this spectrum of tumors, which covers encapsulated common-type PTC
      (EncPTC), EnFVPTC, well-differentiated tumor of uncertain malignant potential
      (WDT-UMP), follicular adenoma (FA) with equivocal PTC-N and minimally invasive
      follicular carcinoma (mFTC). We propose that EnFVPTC and other EnFPLs with
      equivocal PTC-N should be classified into a unified category of borderline
      malignancy, such as well-differentiated tumor of uncertain behavior (WDT-UB),
      based on their homogeneous excellent outcome. It is suggested that the unified
      nomenclature of these lesions may be helpful to reduce significant observer
      disagreements in diagnosis, because complete agreement in the diagnosis of an
      EncPTC, EnFVPTC or FA by all pathologists may be not possible for this
      problematic group of tumors. In conclusion, a malignant diagnosis of EnFVPTC
      should not be used to cover this spectrum of tumors until uncertainty about the
      nature of this lesion is settled, whether it is benign, precancerous or
      malignant.

PMID- 22360503
TI  - Clinical implications of N-cadherin expression in gastric cancer.
AB  - Neo-expression of N-cadherin in cancer cells is regarded as a significant event
      in tumor progression via epithelial-mesenchymal transition (EMT). No reports have
      detailed the clinical impact of N-cadherin expression in gastric cancer. We
      retrospectively examined the co-expression of N-cadherin and E-cadherin in human
      gastric carcinoma and analyzed the clinicopathological significance of N-cadherin
      expression. One hundred and forty-six gastric cancer patients who received
      curative gastrectomy were enrolled. E-cadherin and N-cadherin immunoreactivity in
      cancer tissue was evaluated by the avidin-biotin-peroxidase complex technique.
      The correlation between N-cadherin and E-cadherin expression and
      clinicopathological parameters were analyzed. N-cadherin-positive and -negative
      expression were found in 31 and 115 patients, respectively. N-cadherin expression
      positively correlated with hematogenous recurrence (P < 0.01) and negatively
      correlated with patients' postoperative outcomes (P < 0.05). Moreover, only in
      the E-cadherin-preserved group was prognostic significance found according to N
      cadherin expression (P < 0.01). We could not show a significant relationship
      between N-cadherin expression and EMT in gastric cancer. However, neo N-cadherin
      expression significantly affected patient's survival in gastric cancer.
      Therefore, we concluded that neo N-cadherin expression may be a useful prognostic
      marker independent of E-cadherin expression.

PMID- 22360504
TI  - Breast cancer resistance protein expression is associated with early recurrence
      and decreased survival in resectable pancreatic cancer patients.
AB  - The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even
      after complete resection, with most recurrences occurring within 1-2 years
      postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters
      have been demonstrated to play major roles in multidrug resistance (MDR) of
      cancers. In this study, we evaluated the expression statuses and the clinical
      significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and
      breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by
      immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35
      (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases,
      respectively. The expression statuses of the MDR-related proteins were positively
      correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2
      (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion.
      MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047).
      High BCRP expression in PDAC was a significant prognostic factor for early tumor
      recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR
      related proteins are frequently expressed in PDAC, and high BCRP expression is a
      significant independent predictor for early recurrence and poor survival.
      Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in
      identifying a subgroup of patients with a poor prognosis.

PMID- 22360505
TI  - DEK overexpression is correlated with the clinical features of breast cancer.
AB  - To investigate the clinicopathological significance of DEK overexpression in
      breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of
      intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of
      invasive ductal carcinoma of the breast, were selected from the Department of
      Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK,
      estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had
      higher positivity in DCIS, compared with the adjacent normal breast tissues.
      Also, DEK protein was strongly positive in invasive ductal carcinoma of the
      breast on immunohistochemistry, which was significantly higher than normal breast
      tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast
      showed positive staining for DEK protein. Additionally, DEK overexpression was
      significantly correlated with the increased proliferating index of Ki-67. For the
      histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but
      significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a
      strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%)
      compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%)
      (P<0.05). And DEK protein showed higher expression level in < 3 years disease
      free survival breast cancers than it did in >= 3 years disease free survival
      cases (P<0.05). However, no statistically difference was found among DEK
      expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK
      overexpression appears to be associated with breast cancer progression and DEK
      may potentially be used as a breast cancer biomarker for the early diagnosis,
      prognostic evaluation and therapeutic target for breast cancer.

PMID- 22360506
TI  - Global histone modification pattern associated with recurrence and disease-free
      survival in non-small cell lung cancer patients.
AB  - Global histone modification patterns are presumed to establish epigenetic
      patterns of gene expression and determine the biology of the cell. In the present
      study, the global modification status of histone H3 and H4 was evaluated in 408
      non-small cell lung cancer (NSCLC) tissues by immunostaining. NSCLC showed
      variable staining scores for each antibody. Clinicopathological analyses
      demonstrated a positive correlation between weak nuclear staining for H3K9Ac (P <
      0.001), H3K9TriMe (P= 0.001), H4K16Ac (P < 0.001) and tumor recurrence except
      H4K20 TriMe (P= 0.201). Staining scores of four different antibodies were not
      correlated with other clinicopathologic variables. Patients were further
      clustered according to histone modification patterns: acetylation dominant,
      methylation dominant, co-dominant and modification-negative. The acetylation
      dominant group (P= 0.009) and co-dominant group exhibited less frequent lymph
      node metastasis (P= 0.050), recurrence (P= 0.002) and distant metastasis (P=
      0.010). The acetylation-dominant group showed better prognosis in survival
      analysis (P < 0.001, log-rank), whereas methylation-dominant and modification
      negative status was associated with poor prognosis. In conclusion, our data
      suggest that global histone H3 and H4 modification patterns are potential markers
      of tumor recurrence and disease-free survival in NSCLC patients.

PMID- 22360507
TI  - Trends in prostate needle biopsy diagnosis. A ten year experience of a medical
      center in Taiwan.
AB  - Prostate cancer has seen a rapid rise in Taiwanese men. The current study was
      undertaken to evaluate trends of the disease diagnosed on prostate needle biopsy
      during a ten-year period at the Department of Pathology, Taipei Veterans General
      Hospital. The study included 8236 men who underwent a total of 9995 prostate
      needle biopsies at this institute from 1994 to 2003. Pathologic features
      pertinent to diagnosis of cancer were reviewed and compared for cases diagnosed
      before and after 1999. There were statistically significant increases of the
      overall cancer detection rate (from 17.6% to 19.9%), proportion of cases with a
      Gleason score <= 6 (from 16.6% to 40.9%) and focal adenocarcinoma (from 3.0% to
      12.8%) in the latter 5 years. The incidence of high-grade prostatic
      intraepithelial neoplasia (HGPIN) increased from 0.1% to 1.5%. Patients with
      HGPIN had a significantly higher risk for subsequent cancer discovered on repeat
      biopsy than did those with a primary benign diagnosis (29.9% versus 13.7%).
      Despite a relatively lower incidence of cancer and HGPIN in Taiwanese men
      compared with that reported in Western studies, in recent years we have found an
      increase of relevant diagnoses, especially cancer of limited extent and lower
      grade, which may represent the progress in prostate cancer diagnosis.

PMID- 22360508
TI  - Malignant transformation of exophytic Schneiderian papilloma of the nasal cavity.
AB  - Schneiderian papilloma (SP) is classified into three types: inverted, oncocytic,
      and exophytic. Malignant transformation occurs in 10% of SP; most are inverted
      and oncocytic types. Malignant transformation of polypoid exophytic SP is
      exceptional; only two cases have been reported in the English literature. A 58
      year-old man consulted our hospital because of nasal obstruction. Nasal endoscopy
      and imaging modalities showed a polyp in the right nasal cavity. Biopsy findings
      showed compatibility with SP. However, since fludeoxyglucose positron emission
      tomography (FDG-PET) showed signals, polypectomy was performed. Grossly, the
      polyp was reddish white and measured 2 cm. Histologically, the polyp consisted of
      a non-invasive squamous cell carcinoma (SCC) component (70%), a mature squamous
      component (20%), and Schneiderian epithelium (10%). Vague koilocytosis was
      present in the SCC component. The three components were arranged in an exophytic
      papillary pattern. Immunohistochemically, the non-invasive SCC component was
      positive for cytokeratins (AE1/3, CAM5.2, CK5/6), p63, p53, and Ki67 (labeling
      50%). The mature squamous component was positive for cytokeratins (AE1/3, CAM5.2
      and CK5/6), p63, and Ki67 (labeling 6%). The Schneiderian component was positive
      for cytokeratins (AE1/3, CAM5.2, and CK5/6), p63, and Ki-67 (labeling 4%). The
      tumor was HPV negative in the three components. The polyp was diagnosed as
      exophytic Schneiderian carcinoma arising from exophytic SP. The patient is now
      free from tumor 4 years after the operation.

PMID- 22360509
TI  - Phyllodes tumor of the prostate.
AB  - In this report, we describe a case of phyllodes tumor of the prostate with a high
      value of prostate-specific antigen (PSA). A 47-year-old man with symptoms of
      hematospermia presented with a steadily elevated serum PSA value of 60.76 ng/mL
      (normal range, < 4 ng/mL). A needle biopsy revealed atypical stromal cells
      without any evidence of malignancy. After radical prostatectomy, the tumor
      measured 2.9 cm in diameter and consisted of a single nodule composed of
      irregular, elongated epithelial ducts and atypical stromal cells with enlarged,
      occasionally multinucleated, pleomorphic, or hyperchromatic nuclei.
      Immunohistochemistry showed that the atypical stromal cells were positive for
      vimentin, androgen receptor, estrogen receptor, progesterone, and 5alpha
      reductase, but negative for MIB-1, PSA, SMA, p53, desmin, CD34, c-kit, CD10, S
      100, and EGFR. Excess PSA might be secreted by hyperplastic luminal cells driven
      by 5alpha-reductase-positive stromal and epithelial cells. Array-comparative
      genomic hybridization (array CGH) for genomic alterations revealed a gain of
      11p13, which includes the WT1 gene, and a loss of 1p36.23 and 12p12.1. After
      surgery, the serum PSA value rapidly decreased to within the normal range; no
      recurrence or distant metastasis was noted after 2 years of follow up.

PMID- 22360510
TI  - Unilateral glomerulocystic kidney disease associated with tuberous sclerosis
      complex in a neonate.
AB  - We report a case of glomerular cystic kidney disease (GCKD) associated with
      tuberous sclerosis complex (TSC) in a neonate. The patient displayed progressive
      abdominal enlargement attributed to GCKD associated with TSC. After birth, the
      right kidney was resected because it compressed his liver and right lung, and
      possible malignancy could not be excluded. Macroscopically, the resected kidney
      was markedly enlarged, and histologically the kidney had numerous glomerular
      cysts accompanied by papillary epithelial growth. Notably, a small area of normal
      parenchyma was observed at the lower pole. The epithelial cells of the cysts
      displaying a papillary growth pattern were positive for mTOR, phosphorylated
      mTOR, and phosphorylated S6 ribosomal protein (p-S6). The morphologically
      noncystic, normal-looking tubular epithelium was also positive for p-S6. These
      results imply that one more molecular event might be necessary for cyst formation
      in GCKD associated with TSC, in addition to the activation of mTOR signaling.

PMID- 22360511
TI  - Two cases of ovarian clear cell adenocarcinoma producing estradiol.

PMID- 22360513
TI  - The roles of clinical pharmacologists in formulating medicines policy locally.
AB  - Specialists in Clinical Pharmacology and Therapeutics (CPT) can add value in day
      to-day NHS activities in several ways. They provide a breadth of expertise that
      is not organ-based or disease-specific and that is based on an intimate knowledge
      and understanding of the effectiveness, safety and cost-effectiveness of
      pharmacological interventions. More than any other professional group, they can
      address the growing need for undergraduate and postgraduate teaching to be based
      on 'thoughtful therapeutics', not just the mechanics of prescribing. CPT
      specialists can and do take the lead in making local and national policy
      decisions relating to drug usage and they should be involved in local
      commissioning decisions. Because of the breadth of experience embraced by CPT,
      many clinical pharmacologists have taken on local and national senior clinical
      leadership roles. CPT needs to demonstrate to the NHS, and in particular to
      trainees, that a CPT post in the NHS is a legitimate and rewarding career path,
      where they can use their hard earned CPT skills and expertise to the benefit of
      the NHS as a whole.

PMID- 22360514
TI  - A critical appraisal of the functional evolution of P2Y12 antagonists as
      antiplatelet drugs.
AB  - P2Y12 receptor mediated inhibition of platelet aggregation is one of the most
      explored and exploited pathways in antiplatelet drug therapy to prevent ischemic
      events in patients undergoing percutaneous coronary intervention (PCI) for the
      treatment of the acute coronary syndrome (ACS). Ticlopidine, Clopidogrel,
      Prasugrel, Ticagrelor, Cangrelor and Elinogrel are the P2Y12 inhibitors that act
      as antiplatelet drugs. In this review, the features of these drugs and the
      factors reported to be responsible for drug resistance or drug ineffectiveness
      were described. The features like drug metabolism, reversible or irreversible
      binding of drugs to their target protein and the mode of administration were
      observed to evolve along with the antiplatelet drugs. These features also include
      the drug-drug interactions, the pharmacogenetics and pharmacodynamics of P2Y12
      inhibitors. We attempted to critically analyze how the desirable features were
      met by the P2Y12 inhibitors in the course of time. This review provides an
      overview of the evolution of P2Y12 inhibitors and may guide the researchers to
      develop better antiplatelet drugs in the future.

PMID- 22360515
TI  - The performance advantage of a high resting metabolic rate in juvenile salmon is
      habitat dependent.
AB  - 1. Basal levels of metabolism vary significantly among individuals in many taxa,
      but the effects of this on fitness are generally unknown. Resting metabolic rate
      (RMR) in juvenile salmon and trout is positively related to dominance status and
      ability to obtain a feeding territory, but it is not clear how this translates
      into performance in natural conditions. 2. The relationships between RMR,
      dominance, territoriality and growth rates of yearling Atlantic salmon Salmo
      salar were examined in relation to predictability in food supply and habitat
      complexity, using replicate sections of a large-scale controlled semi-natural
      stream. 3. Estimated RMR was a strong predictor of dominance, and under
      conditions of a predictable food supply in a structurally simple habitat, high
      estimated RMR fish obtained the best feeding territories and grew faster. 4. When
      the spatial distribution of food was made less predictable, dominant (high
      estimated RMR) fish were still able to occupy the most profitable feeding
      locations by periodically moving location to track the changes in food
      availability, but RMR was no longer a predictor of growth rate. Moreover, when a
      less predictable food supply was combined with a visually more complex (and
      realistic) habitat, fish were unable to track changes in food availability, grew
      more slowly and exhibited greater site fidelity, and there were no relationships
      between estimated RMR and quality of occupied territory or growth rate. 5. The
      relative benefit of RMR is thus context dependent, depending on both habitat
      complexity and the predictability of the food supply. Higher habitat complexity
      and lower food predictability decrease the performance advantages associated with
      a high RMR.

PMID- 22360517
TI  - Molecular phylogenetics of Floridosentis ward, 1953 (Acanthocephala:
      Neoechinorhynchidae) parasites of mullets (Osteichthyes) from Mexico, using 28S
      rDNA sequences.
AB  - Species of Floridosentis (Acanthocephala) are common parasites of mullets (Mugil
      spp., Mugilidae) found in tropical marine and brackish water in the Americas.
      Floridosentis includes 2 species distributed in Mexico, i.e., Floridosentis
      pacifica, restricted to the Pacific Ocean near Salina Cruz, Oaxaca, and
      Floridosentis mugilis, distributed along the coast of the Pacific Ocean and the
      Gulf of Mexico. We sampled 18 populations of F. mugilis and F. pacifica (12 from
      the Pacific and 6 from the Gulf of Mexico) and sequenced a fragment of the rDNA
      large subunit to evaluate phylogenetic relationships of populations of
      Floridosentis spp. from Mexico. Species identification of museum specimens of F.
      mugilis from the Pacific Ocean was confirmed by examination of morphology traits.
      Phylogenetic trees inferred with maximum parsimony, maximum likelihood, and
      Bayesian inference indicate that Floridosentis is monophyletic comprising of 2
      major well-supported clades, the first clade corresponding to F. mugilis from the
      Gulf of Mexico, and the second to F. pacifica from the Pacific Ocean. Genetic
      divergence between species ranged from 7.68 to 8.60%. Intraspecific divergence
      ranged from 0.14 to 0.86% for F. mugilis and from 1.72 to 4.49% for F. pacifica.
      Data obtained from diagnostic characters indicate that specimens from the Pacific
      Ocean in Mexico have differences in some traits among locations. These results
      are consistent with the phylogenetic hypothesis, indicating that F. pacifica is
      distributed in the Pacific Ocean in Mexico with 3 major lineages.

PMID- 22360518
TI  - A clinical comparison of penetrating and blunt traumatic brain injuries.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of injury death and
      long-term disability in the USA. It commonly results from blunt (closed) or
      penetrating trauma. The majority of civilian TBI is caused by falls or motor
      vehicle collisions, whereas military TBI mainly results from explosions. Although
      penetrating injuries are less common than closed injuries in the civilian
      population, they are far more lethal. Unfortunately, the pathophysiologic
      differences between penetrating and closed TBI remain poorly understood due to
      the lack of studies on the subject. Many studies on the prognostic factors of
      mortality and functional outcome after TBI exclude penetrating brain injuries
      from their series because they are believed to have a different pathophysiology.
      METHODS: 125 Articles regarding brain injury were reviewed and summarized for
      this report. RESULTS: Despite the absence of a clear delineation between
      penetrating and blunt TBI, the current guidelines for penetrating TBI suggest
      defaulting to management strategies used for closed TBI with limited supportive
      evidence. Thus, injuries that appear to have different pathophysiologies and
      outcomes are managed equally and perhaps not optimally. CONCLUSION: In view of
      the incomplete understanding of the impact of mechanism of injury on TBI
      outcomes, as demonstrated in the current review, new research studies are
      required to improve evidence-based TBI guidelines tailored especially for
      penetrating injuries.

PMID- 22360519
TI  - A cognitive behaviour therapy (CBT) programme for anxiety following moderate
      severe traumatic brain injury (TBI): two case studies.
AB  - BACKGROUND: CBT is a potentially effective treatment for anxiety disorders
      following TBI; however, empirical evidence has mainly come from clients with mild
      TBI. This paper describes a CBT-based anxiety treatment programme adapted for
      clients with more severe injuries. Two case studies are provided to illustrate
      the implementation of the programme, as a step toward larger scale testing of the
      programme's feasibility. METHODS AND PROCEDURES: A manualised adapted CBT
      treatment manual was used to deliver CBT in a standardised manner to two clients,
      one with severe and one with moderate TBI. Outcome was evaluated using a single
      subject design with repeated measures of anxiety, mood and coping style at pre-
      and post-CBT. RESULTS: The two clients demonstrated positive treatment response
      on either a measure of anxiety or a continuous measure of distress. Although
      neither demonstrated a clinically significant change according to the primary
      outcome measure (Hospital Anxiety and Depression Scale), they showed significant
      change in at least one corroborated measure of anxiety. CONCLUSIONS: This study
      suggests the potential utility of the adapted CBT programme for clients with
      moderate-severe TBI. Limitations of the single case studies were discussed, while
      noting how they would be addressed in a follow-up randomised controlled trial.

PMID- 22360520
TI  - Lifetime history of traumatic brain injury among persons with substance use
      disorders.
AB  - OBJECTIVE: Determine (a) if there are sub-groups of individuals with substance
      use disorders distinguished by their pattern of sustaining traumatic brain injury
      (TBI) over the lifetime and (b) whether sub-group membership affects current
      functioning. DESIGN: Secondary analysis. SETTINGS: Outpatient substance abuse
      treatment programme and state prison. PARTICIPANTS: Two hundred and fifty-seven
      participants with lifetime histories of both TBI and substance used disorder
      drawn from two previous studies of (a) persons in substance abuse treatment and
      (b) prison inmates. MAIN OUTCOME MEASURES: Ohio State University TBI
      Identification Method, speed of information processing, working memory,
      disinhibition, cognitive complaints, sociopathy and substance use disorder
      severity. RESULTS: Seven clusters of lifetime history of TBI were characterized
      by the severity of injuries, age at occurrence and presence of a period of time
      when multiple mild injuries were incurred, often receiving no medical attention.
      Cluster membership contributed to the prediction of cognitive performance (i.e.
      processing speed), self-reported cognitive problems and alcohol and other drug
      severity. CONCLUSIONS: In addition to injury severity, age at injury and periods
      of repeated injury may be distinguishing aspects of a lifetime history of TBI for
      persons with substance use disorders. Results suggest that clinicians would
      benefit from knowledge of a person's full history of TBI.

PMID- 22360522
TI  - Upper-limb virtual rehabilitation for traumatic brain injury: a preliminary
      within-group evaluation of the elements system.
AB  - AIM: The aim of this study was to assess the efficacy of the Elements virtual
      reality (VR) system for rehabilitation of upper-limb function in patients with
      traumatic brain injury (TBI). METHODS: Using a within-group design, patients were
      tested three times, each 4 weeks apart: Pre-intervention 1 and 2 and Post
      intervention. During intervention, participants received 12 1-hour training
      sessions over 4 weeks in addition to their usual care. Five males and four
      females aged 18-48 years with severe TBI were recruited. The Elements system
      consisted of a 100-cm tabletop LCD, camera tracking system, tangible user
      interfaces (i.e. graspable objects of basic shape) and software. The system
      provided two modes of interaction with augmented feedback: goal-directed and
      exploratory. Upper-limb performance was assessed using system-rated measures
      (movement speed, accuracy and efficiency) and standardized tests. RESULTS:
      Planned comparisons revealed little change in performance over the pre-test
      period apart from an increase in movement speed. There were significant training
      effects, with large effect sizes on all measures except the nuts-and-bolts task.
      CONCLUSIONS: These preliminary findings support the results of an early case
      study of the Elements system, further demonstrating that VR training is a viable
      adjunct to conventional physical therapy in facilitating motor learning in
      patients with TBI.

PMID- 22360521
TI  - Mild traumatic brain injury (MTBI) leads to spatial learning deficits.
AB  - PRIMARY OBJECTIVE: The aim of this study was to investigate the effect of mild
      and severe TBI on young male Wistar rats' spatial learning. RESEARCH DESIGN:
      Randomized repeated measure experimental design was used to examine spatial
      learning in three independent animal groups. METHODS AND PROCEDURES: Twenty-four
      (severe n = 9, mild n = 8, sham n = 7) male rats were included in the study.
      Animals received controlled mild (1.5 mm), severe (2.5 mm) cortical impact injury
      or sham surgery. Spatial learning was assessed daily using a modified Morris
      water maze test, 20 days post-trauma, for 5 consecutive days. Percentage time
      travelled within each quadrant and escape latency were calculated. All animals'
      hippocampal brain regions were examined post-injury using neuron (MAP2) and pre
      synaptic protein (Synaptophysin) biomarkers. MAIN OUTCOMES AND RESULTS: It took
      the animals with mild injury until day 3 to reach the platform; and animals with
      mild and severe injury spent significantly less time in the target quadrant than
      the sham. The hippocampal neuron numbers differed proportionately between animals
      with severe and mild injury, but the percentage of synaptophysin density was
      significantly less in the dentate gyrus of both animals with mild and severe
      injury than sham group. CONCLUSION: Persistent spatial learning deficits exist
      after mild TBI; these deficits appear equivalent to deficits exhibited after a
      more severe injury.

PMID- 22360523
TI  - Advancing the health and quality-of-life of girls and women after traumatic brain
      injury: workshop summary and recommendations.
AB  - PURPOSE: To disseminate findings from an international workshop regarding
      priority issues for girls' and women's health and quality-of-life after
      sustaining a traumatic brain injury (TBI). METHODS: A workshop was held prior to
      the American Congress of Rehabilitation Medicine Conference 2010. The purpose of
      the workshop was to highlight the unique health issues experienced by women after
      a TBI, to identify research, education and policy gaps and to develop strategies
      to promote women's health. Presentations by researchers and consumers as well as
      large group discussions formed the basis of the recommendations. RESULTS: Twenty
      researchers, clinicians, consumers and community agency personnel attended from
      five countries. Significant gaps in service provision in the community were
      identified as were unique issues for the short- and long-term effects on
      maturation and ageing, reproductive and sexual health, mental health and life
      satisfaction. The workshop led to the development of an international task force
      and recommendations for future directions. CONCLUSION: Women and girls experience
      unique outcomes after a TBI. The workshop identified research, policy, education
      and service priorities for the promotion of health and quality-of-life within
      this population.

PMID- 22360524
TI  - Health-related quality-of-life after traumatic brain injury: a 2-year follow-up
      study in Wuhan, China.
AB  - OBJECTIVE: To assess health-related quality-of-life (HRQoL) 2 years after
      traumatic brain injury (TBI) among a group of Chinese. METHODS: A total of 358
      adult patients with moderate-to-severe TBI based on Glasgow Coma Scale score were
      recruited in a large trauma centre in Wuhan, China during May 2005 to April 2008.
      They were followed up for 2 years and the Medical Outcome Short Form 36 was used
      to measure HRQoL. RESULTS: After a 2-year follow-up, there were 312 (87.2%)
      survivors. All domains of HRQoL had the lowest scores at discharge, greatly
      improved over the first 6 months and showed continued improvement. Patients with
      TBI still had significantly lower scores in every domain than the reference group
      2 years after discharge. Female patients had lower MCS scores than the males (OR
      = 1.8, 95% CI: 1.1-2.9). Patients older than 30 had lower scores in PCS (OR =
      1.7, 95% CI: 1.1-2.6). Patients with severe TBI had lower scores in both PCS (OR
      = 1.9, 95% CI: 1.2-3.1) and MCS (OR = 1.6, 95% CI: 1.0-2.6) compared with those
      with moderate TBI. CONCLUSIONS: HRQoL of a group of Chinese patients with TBI
      improved during 2 years after discharge. Age, sex and severity of TBI were
      significantly associated with physical or mental HRQoL after discharge.

PMID- 22360525
TI  - Disorders of consciousness: preliminary data supports added value of extended
      behavioural assessment.
AB  - BACKGROUND: The use of validated behavioural assessment scales in assessment of
      patients with Disorders of Consciousness (DOC) is well established. However,
      there is little evidence to guide decisions on total time spent in behavioural
      assessment. OBJECTIVE: To assess whether brief behavioural assessment was as
      effective as extended behavioural assessment in detecting non-vegetative
      behaviours. METHODS: Consecutive patients with suspected DOC were assessed with
      two standardized instruments: Coma Recovery Scale Revised (CRS-R) and Sensory
      Modality Assessment and Rehabilitation Technique (SMART). Assessors were blinded
      to results from the other scale at the point of assessment. Two administrations
      of CRS-R together took 50-60 minutes ('brief' assessment). One complete SMART
      assessment took 600 minutes ('extended' assessment). Patients were classified as
      being in a vegetative state (VS) or minimally conscious state (MCS)/emerged from
      minimally conscious state (EMCS), following brief and extended assessment.
      RESULTS: Ten patients were assessed. Brief and extended assessment yielded the
      same diagnostic category (VS or MCS) for six patients and different categories
      for four, with extended assessment detecting higher level behaviours.
      CONCLUSIONS: Brief behavioural assessment was not as effective as extended
      assessment in detecting non-vegetative behaviours. Total time spent in
      behavioural assessment is likely important. Further studies and clearer clinical
      guidance are needed.

PMID- 22360526
TI  - Importance of an intact dura in management of compound elevated fractures; a
      short series and literature review.
AB  - PURPOSE: To describe compound elevated fractures (CEFs) of the skull vault, with
      radiological pictures, management problems and prognosticative factors. METHOD:
      The authors describe three cases of CEFs of the cranium, their mode of injury,
      clinical findings, radiological images and management problems. The authors have
      reviewed the existing literature regarding epidemiological data, neurological
      status, dural breech, methods of management and final outcome, in respect of
      CEFs. RESULTS: The first case had no dural breech, the second case had completely
      shattered dura, with extruding brain matter from the wound, while the third case
      had an elevated bone flap in consequence to large extradural haematoma. The
      patients with intact dura had relatively favourable outcome, when compared to
      patients with shattered dura. Three cases are added to the existing 10 such cases
      described in English literature. The major cause of unfavourable outcome remains
      sepsis and the presence of intact dura places these cases in the relatively safe
      category, regarding infective complications. CONCLUSION: The authors attempt at
      highlighting the importance of intact dura with such an injury. The review of
      literature supports favourable outcomes in patients having no dural breech.

PMID- 22360528
TI  - Antarctic DNA moving forward: genomic plasticity and biotechnological potential.
AB  - Antarctica is the coldest, driest, and windiest continent, where only cold
      adapted organisms survive. It has been frequently cited as a pristine place, but
      it has a highly diverse microbial community that is continually seeded by
      nonindigenous microorganisms. In addition to the intromission of 'alien'
      microorganisms, global warming strongly affects microbial Antarctic communities,
      changing the genes (qualitatively and quantitatively) potentially available for
      horizontal gene transfer. Several mobile genetic elements have been described in
      Antarctic bacteria (including plasmids, transposons, integrons, and genomic
      islands), and the data support that they are actively involved in bacterial
      evolution in the Antarctic environment. In addition, this environment is a
      genomic source for the identification of novel molecules, and many investigators
      have used culture-dependent and culture-independent approaches to identify cold
      adapted proteins. Some of them are described in this review. We also describe
      studies for the design of new recombinant technologies for the production of
      'difficult' proteins.

PMID- 22360529
TI  - De novo reestablishment of gap junctional intercellular communications during
      reprogramming to pluripotency and differentiation.
AB  - Gap junctional intercellular communication (GJIC) has been described in embryonic
      stem cells (ESCs) and various somatic cells. GJIC has been implicated in the
      regulation of cell proliferation, self-renewal, and differentiation. Recently, a
      new type of pluripotent stem cells was generated by direct reprogramming of
      somatic cells. Here, for the first time, we show that during reprogramming events
      GJIC is re-established upon reaching complete reprogramming. The opposite process
      of cell differentiation from the pluripotent state leads to the disruption of
      GJIC between pluripotent and differentiated cell subsets. However, GJIC is
      subsequently re-established de novo within each differentiated cell type in
      vitro, forming communication compartments within a histotype. Our results provide
      the important evidence that reestablisment of functional gap junctions to the
      level similar to human ESCs is an additional physiological characteristic of
      somatic cell reprogramming to the pluripotent state and differentiation to the
      specific cell type.

PMID- 22360530
TI  - Diepoxide-triggered conformational transition of silk fibroin: formation of
      hydrogels.
AB  - Silk fibroin hydrogels with tunable properties could be obtained from aqueous
      fibroin solutions (4.2 w/v %) in a short period of time. This was achieved by the
      addition of ethylene glycol diglycidyl ether (EGDE) into the reaction solution.
      Introduction of EGDE cross-links between the fibroin molecules decreases the
      mobility of the chains, which triggers the conformational transition from random
      coil to beta-sheet structure and hence fibroin gelation. Dynamic rheological
      measurements conducted at 50  degrees C show the formation of strong to weak
      hydrogels depending on the pH of the reaction solution. Although EGDE attacks the
      amino groups of fibroin and forms interstrand cross-links, beta-sheets acting as
      physical cross-links dominate the elasticity of the hydrogels. Mechanical
      response of low-modulus fibroin hydrogels formed above pH 9.7 is highly nonlinear
      with strong strain hardening behavior (700%) arising from the alignment of the
      crystallizable amino acid segments.

PMID- 22360531
TI  - Preparation and characterization of low dispersity anionic multiresponsive core
      shell polymer nanoparticles.
AB  - We prepared anionic multistimuli responsive core-shell polymer nanoparticles with
      very low size dispersity. By using either acrylic acid (AA) or methacrylic acid
      (MA) as a comonomer in the poly(N-isopropyl acrylamide) (PNIPAM) shell, we are
      able to change the distribution of negative charges in the nanoparticle shell.
      The particle size, volume phase transition temperature, and aggregation state can
      be modulated using temperature, pH, or ionic strength, providing a very versatile
      platform for applications in sensors, medical diagnostics, environmental
      remediation, etc. The nanoparticles have a glassy poly(methyl methacrylate)
      (PMMA) core of ca. 40 nm radius and a cross-linked PNIPAM anionic shell with
      either AA or MA comonomers. The particles, p(N-AA) and p(MA-N), respectively,
      have the same total charge but different charge distributions. While the p(MA-N)
      particles have the negative charges preferentially distributed toward the inner
      shell, in the case of the p(N-AA) particles the charge extends more to the
      particle outer shell. The volume phase transition temperature (T(VPT)) of the
      particles is affected by the charge distribution and can be fine-tuned by
      controlling the electrostatic repulsion on the particle shell (using pH and ionic
      strength). By suppressing the particle charge we can also induce temperature
      driven particle aggregation.

PMID- 22360532
TI  - The ecology of viruses that infect eukaryotic algae.
AB  - Because viruses of eukaryotic algae are incredibly diverse, sweeping
      generalizations about their ecology are rare. These obligate parasites infect a
      range of algae and their diversity can be illustrated by considering that
      isolates range from small particles with ssRNA genomes to much larger particles
      with 560 kb dsDNA genomes. Molecular research has also provided clues about the
      extent of their diversity especially considering that genetic signatures of algal
      viruses in the environment rarely match cultivated viruses. One general concept
      in algal virus ecology that has emerged is that algal viruses are very host
      specific and most infect only certain strains of their hosts; with the exception
      of viruses of brown algae, evidence for interspecies infectivity is lacking.
      Although some host-virus systems behave with boom-bust oscillations, complex
      patterns of intraspecies infectivity can lead to host-virus coexistence
      obfuscating the role of viruses in host population dynamics. Within the framework
      of population dynamics, host density dependence is an important phenomenon that
      influences virus abundances in nature. Variable burst sizes of different viruses
      also influence their abundances and permit speculations about different life
      strategies, but as exceptions are common in algal virus ecology, life strategy
      generalizations may not be broadly applicable. Gaps in knowledge of virus
      seasonality and persistence are beginning to close and investigations of
      environmental reservoirs and virus resilience may answer questions about virus
      inter-annual recurrences. Studies of algal mortality have shown that viruses are
      often important agents of mortality reinforcing notions about their ecological
      relevance, while observations of the surprising ways viruses interact with their
      hosts highlight the immaturity of our understanding. Considering that just two
      decades ago algal viruses were hardly acknowledged, recent progress affords the
      optimistic perspective that future studies will provide keys to unlocking our
      understanding of algal virus ecology specifically, and aquatic ecosystems
      generally.

PMID- 22360533
TI  - Chalcone-benzoxaborole hybrid molecules as potent antitrypanosomal agents.
AB  - We report the novel chalcone-benzoxaborole hybrids and their structure-activity
      relationship against Trypanosoma brucei  parasites. The 4-NH(2) derivative 29 and
      3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH(2)
      3-OMe compound 49 showed an IC(50) of 0.010 MUg/mL and resulted in 100% survival
      and zero parasitemia in a murine infection model, which represents one of the
      most potent compounds discovered to date from the benzoxaborole class that
      inhibit  T. brucei  growth.

PMID- 22360534
TI  - Misconceptions predict dropout and poor adherence prospectively among newly
      admitted first-time methadone maintenance treatment clients in Guangzhou, China.
AB  - AIMS: To investigate the incidence of dropout and the prevalence of poor
      adherence among newly admitted first-time clients of methadone maintenance
      treatment (MMT) clinics, and the associations between MMT-related misconceptions
      and these two treatment outcomes. DESIGN: A cohort study (maximum follow-up
      period = 17.6 months) was conducted. SETTING: Three of the nine MMT clinics in
      Guangzhou, China participated in the study. PARTICIPANTS: The sample included 158
      newly admitted first-time MMT clients. MEASUREMENTS: Information collected
      included background characteristics, history of drug use, MMT-related
      misconceptions, dropout during the entire study period and poor adherence within
      the first 6 months since admission to MMT. FINDINGS: Of all newly admitted MMT
      clients, 98.2% possessed at least one and 50.6% possessed all four types of MMT
      related misconception; 51.3% had dropped out before the completion of the study
      [95% confidence interval (CI): 43.5-59.1%] and 62% exhibited poor adherence
      within the first 6 months since admission (95% CI: 54.2-69.6%). Adjusting for
      significant background variables, the number of misconceived responses predicted
      significantly both dropout [hazard ratio (HR) = 3.80 for two to three
      misconceived items, HR = 7.13 for four misconceived items, with zero to one
      misconceived item being the reference] and poor adherence within the first 6
      months [relative risk (RR) = 4.13 for two to three misconceived items; RR = 4.40
      for four misconceived items, with zero to one misconceived item being the
      reference. CONCLUSIONS: Among opiate addicts in China prescribed methadone
      maintenance therapy for the first time, misconceptions about this medication are
      prevalent and are associated with poor adherence to the medication regimen and a
      high a rate of dropout from the treatment programme.

PMID- 22360535
TI  - Neural network application in Japanese sign language: distinction of similar
      Yubimoji gestures.
AB  - In a previous paper, the authors built a neural network model to recognize
      Japanese sign language syllabary or yubimoji. One of the problems encountered in
      that study was the accurate digital representation and distinction of similar
      yubimoji gestures, i.e. gestures with the same finger flexure positions but with
      different hand/finger orientations. This study focuses on these yubimoji
      gestures. Using data from a glove interface with bend sensors and accelerometers,
      a neural network was built, trained and tested. The network performed well and
      good results were obtained.

PMID- 22360536
TI  - Provision of medicines information: the example of the British National
      Formulary.
AB  - A national war formulary, published during the Second World War, was succeeded by
      hardback books called British National Formularies (BNFs), which were produced by
      the British Medical Association and the Royal Pharmaceutical Society about every
      3 years until 1976. In 1981 a greatly revised and improved softback version was
      published and it has been revised and published twice a year since. It has
      acquired a reputation for being reliable, relevant and up to date. In 2005 the
      BNF for Children (BNFC) appeared and it has been revised and published every year
      since. Both BNFs have been used extensively in training prescribers and
      dispensers, they have supported increasing numbers of 'non-medical' prescribers
      and overseas use has grown. The current challenge is to provide the BNF data
      electronically, as three examples show. First, the contents of the BNF and BNFC
      are available digitally at BNF.org and BNFC.org, and via mobile devices, which
      require internet access, or as a download, which does not. Secondly,
      FormularyComplete is a system that enables hospitals, regions, or even countries
      to create their own formularies, by adding information on costs, local policies
      and drug availability to an intranet version of the BNF, a data source that
      cannot be modified. Thirdly, the BNF is working with others to provide the BNF
      data as computer-readable content, to support electronic prescribing and
      medicines management. Whatever systems are used, the information on drugs must be
      reliable and, ideally, all prescribers and dispensers in the UK should be guided
      by the same data source.

PMID- 22360537
TI  - Acute effects of thymoquinone on the pregnant rat and embryo-fetal development.
AB  - The effect of a single intraperitoneal (i.p.) injection of thymoquinone (TQ) on
      the pregnant rat and embryo-fetal development was investigated. Pregnant female
      Wistar rats received 15, 35, and 50 mg/kg body weight of TQ i.p. on day 11 or 14
      of gestation, and on day 18 of gestation they were sacrificed and laparotomized.
      Results showed that TQ induces maternal and embryonic toxicities in a dose- and
      time-dependent manner. With a dose of 50 mg/kg, treated rats experienced a
      significant decrease in maternal body weight and complete fetal resorption when
      the dose was given on day 11 of gestation. On the other hand, 46.2% of implants
      were resorbed and the viable fetuses showed no TQ-related malformations when the
      dose was given on day 14 of gestation. At a lower TQ dose of 35 mg/kg, maternal
      and embryonic toxicities were observed only when it was given on day 11 of
      gestation. The dose of 15 mg/kg was considered to be a dose with no observed
      adverse effect level for maternal and embryo-fetal toxicities when it was given
      day 11 or 14 of gestation. Based on the results of this study, TQ, at doses of 50
      and 35 mg/kg, has a potentially disruptive effect on embryonic development during
      the second trimester of rat pregnancy.

PMID- 22360538
TI  - Cervical leiomyomas in pregnancy: report of 17 cases.
AB  - AIM: To analyse the management strategies and delivery outcomes of women with
      cervical leiomyomas in pregnancy. METHODS: We retrospectively analysed the
      pregnancy outcomes of 17 women with cervical leiomyomas. The outcome measures
      assessed included the volume of blood loss at delivery, need for blood
      transfusion, intra- and post-operative complications and length of hospital stay.
      RESULTS: The mean diameter of the leiomyomas was 10.4 +/- 7.2 cm, with a range of
      3-30 cm. The mean blood loss was 697 +/- 394 mL (range of 350-4200 mL). Six women
      (35.3%) required a blood transfusion. The mean duration of stay in hospital after
      delivery was 7.9 +/- 3.9 days (range 4-20 days). There were three cases of severe
      haemorrhage or infection post-operation necessitating hysterectomy, and all of
      the leiomyomas in these cases were more than 20 cm in diameter. There was a
      positive correlation between the blood loss volume and the size of leiomyomas
      (correlation coefficient 0.638, P < 0.01). CONCLUSIONS: The dimensions of
      cervical leiomyomas influences post-partum blood loss. Large cervical leiomyomas
      appear associated with adverse outcomes. When the leiomyomas are relatively
      small, an experienced practitioner could consider myomectomy during a caesarean
      delivery.

PMID- 22360539
TI  - Lattice dynamics of beta-V2O5: Raman spectroscopic insight into the atomistic
      structure of a high-pressure vanadium pentoxide polymorph.
AB  - We report here the Raman spectrum and lattice dynamics study of a well
      crystallized beta-V(2)O(5) material prepared via a high-temperature/high-pressure
      (HT/HP) route, using alpha-V(2)O(5) as the precursor. Periodic quantum-chemical
      density functional theory calculations show good agreement with the experimental
      results and allow one to assign the observed spectral features to specific
      vibrational modes in the beta-V(2)O(5) polymorph. Key structure-spectrum
      relationships are extracted from comparative analysis of the vibrational states
      of the beta-V(2)O(5) and alpha-V(2)O(5) structures, and spectral patterns
      specific to the basic units of the two V(2)O(5) phases are proposed for the first
      time. Such results open the way for the use of Raman spectroscopy for the
      structural characterization of vanadium oxide-based host lattices of interest in
      the field of lithium batteries and help us to greatly understand the atomistic
      mechanism involved in the alpha-to-beta phase transition of vanadium pentoxide.

PMID- 22360540
TI  - Overview of the [corrected] travoprost /timolol BAK-free fixed combination.
AB  - INTRODUCTION: Glaucoma is the second leading cause of blindness globally,
      representing a significant public health concern. More than 60 million people are
      affected by glaucoma worldwide; as this population ages, the number is expected
      to increase. Glaucoma is a collection of heterogeneous diseases sharing common
      clinical characteristics. The goal of treatment is to prevent significant visual
      dysfunction through reduction of intraocular pressure (IOP). AREAS COVERED: This
      is a review of the current literature about combination therapeutic regimens for
      the reduction of IOP, focusing on the risk : benefit profile of a fixed
      combination therapy using travoprost and timolol. EXPERT OPINION: Since the debut
      of prostaglandin analogues in the 1990s, only modest innovation has occurred in
      glaucoma pharmacology. A growing body of research has established that the
      preservative benzalkonium chloride (BAK) might not be the benign contributor
      expected of excipient ingredients. Thus, BAK-free treatments were developed, with
      the goal of IOP reduction without furthering ocular surface disease symptoms. The
      BAK-free travoprost/timolol combination represents an important addition to
      glaucoma medication options and may fill an unmet need in this therapeutic arena.

PMID- 22360541
TI  - Insulin resistance at diagnosis in Japanese children with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Insulin resistance at diagnosis was investigated in Japanese children
      with type 2 diabetes mellitus (T2DM). METHODS: A total of 160 children with T2DM
      were divided into groups on the basis of percent overweight at time of diagnosis:
      group A (n = 28), <20%; group B (n = 55), 20-39%; group C (n = 37), 40-59%; group
      D (n = 40), >= 60%. Indicators of insulin resistance at diagnosis were compared
      among the four patient groups, and also between the children with T2DM and the
      201 age-matched normal Japanese children. RESULTS: There were no significant
      differences in plasma glucose (PG) levels among the four patient groups. The mean
      concentration of fasting plasma immunoreactive insulin (IRI) was significantly
      higher in group D than in groups A and B (39.2 uU/mL vs 16.2 uU/mL and 24.1
      uU/mL, P < 0.05, respectively). The mean homeostasis model assessment (HOMA-R)
      was significantly higher in group D than in all the other three groups (17.6 vs
      7.8, 10.8 and 12.7, P < 0.05, respectively). The indicators HOMA-R and fasting
      IRI were significantly higher in each diabetes group, even in non-obese group A,
      than in normal children (P < 0.01, respectively). CONCLUSIONS: Japanese children
      with T2DM had insulin resistance at diagnosis regardless of percent overweight,
      and the degree of insulin resistance gradually increased with rise in percent
      overweight.

PMID- 22360542
TI  - Antenatal neurodevelopmental defects in ornithine transcarbamylase deficiency.

PMID- 22360543
TI  - Early and mid-term clinical outcome of emergency PCI in patients with STEMI due
      to unprotected left main coronary artery disease.
AB  - OBJECTIVES: Evaluation of acute and mid-term outcomes of patients with ST
      elevation myocardial infarction (STEMI) undergoing emergency PCI due to
      unprotected left main coronary artery (ULMCA) disease. BACKGROUND: STEMI patients
      due to ULMCA disease represent a rare, high risk group. Percutaneous coronary
      intervention (PCI) may be the preferred strategy of myocardial revascularization
      but there are few data about this topic. METHODS: We analyzed 30-day and mid-term
      mortality of 58 patients with STEMI and ULMCA disease as culprit lesion treated
      in our centre by emergency PCI between 2000 to 2010. RESULTS: Mean age was 67.3
      +/- 11.5 years. Thirty (51.7%) patients had cardiogenic shock on admission. PCI
      success was achieved in 54 patients (93.1%). Mean follow-up was 15.8 +/- 10.9
      months (median 14, range 6-45). Thirty-day and mid-term mortality rates were
      39.7% and 44%. Backward binary logistic regression model identified cardiogenic
      shock at presentation (OR 12.6, 95% CI 2.97-53.6, P < 0.001), age >=75 years (OR
      5.9, 95% CI 1.3-26.5, P = 0.019) and post-PCI TIMI flow grade <3 (OR 2.9, 95% CI
      1.8-5.7 P = 0.02) as independent predictors of 30-day mortality. Cox proportional
      hazard ratio (HR) identified shock at presentation (HR 5.2, 95% CI 1.8-14.3, P <
      0.002), age >=75 years (HR 3.9, 95% CI 1.8-8.7, P < 0.001), post-PCI TIMI flow
      grade <3 (HR 4.9, 95% CI 1.6-14.6; P < 0.005) as independent predictors of mid
      term mortality. CONCLUSIONS: In patients with STEMI and ULMCA as culprit lesion,
      emergency PCI is a valuable therapeutic strategy. Early and mid-term survival
      depends on cardiogenic shock, advanced age, and PCI failure. Patients surviving
      the first month have good mid-term prognosis.

PMID- 22360544
TI  - Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes
      and intradialytic hypotension: a case-control study.
AB  - Amyloid fibrils can affect vascular structure through deposition and by causing
      nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients
      with amyloidosis are prone to development of hypotension. Hypotension may also
      affect the maturation of arteriovenous fistula (AVF) and may set the stage for
      formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects
      of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a
      case-control study which included 20 hemodialysis patients with amyloidosis and
      20 hemodialysis patients without amyloidosis as control group. All patients
      underwent Doppler ultrasound of AVF. A thorough fistula history and baseline
      laboratory values along with episodes of intradialytic hypotension and blood
      pressure measurements were recorded. There was no difference between the groups
      regarding age, gender, body mass index, presence of comorbidities, hypertension,
      and drug use. Systolic and diastolic blood pressures were similar (119 +/- 28/75
      +/- 17 and 120 +/- 14/75 +/- 10 mmHg for patients with and without amyloidosis,
      respectively). Intradialytic hypotension episodes were also similar. Patients
      with amyloidosis had significantly lower serum albumin and higher C-reactive
      protein values compared to control hemodialysis patients. AVF sites and total
      number of created fistulas were similar in both groups. Flow rates of current
      functional AVFs were not different between the groups (1084 +/- 875 and 845 +/-
      466 mL/minute for patients with and without amyloidosis, respectively, p:0.67).
      Patency duration of first AVF was not different between the groups. Clinical
      fistula outcomes and rate of intradialytic hypotension episodes were not
      significantly different between patients with and without secondary systemic
      amyloidosis.

PMID- 22360545
TI  - Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies
      for therapeutic intervention.
AB  - Protein misassembly into aggregate structures, including cross-beta-sheet amyloid
      fibrils, is linked to diseases characterized by the degeneration of post-mitotic
      tissue. While amyloid fibril deposition in the extracellular space certainly
      disrupts cellular and tissue architecture late in the course of amyloid diseases,
      strong genetic, pathological and pharmacologic evidence suggests that the process
      of amyloid fibril formation itself, known as amyloidogenesis, likely causes these
      maladies. It seems that the formation of oligomeric aggregates during the
      amyloidogenesis process causes the proteotoxicity and cytotoxicity characteristic
      of these disorders. Herein, we review what is known about the genetics,
      biochemistry and pathology of familial amyloidosis of Finnish type (FAF) or
      gelsolin amyloidosis. Briefly, autosomal dominant D187N or D187Y mutations
      compromise Ca(2+) binding in domain 2 of gelsolin, allowing domain 2 to sample
      unfolded conformations. When domain 2 is unfolded, gelsolin is subject to
      aberrant furin endoproteolysis as it passes through the Golgi on its way to the
      extracellular space. The resulting C-terminal 68 kDa fragment (C68) is
      susceptible to extracellular endoproteolytic events, possibly mediated by a
      matrix metalloprotease, affording 8 and 5 kDa amyloidogenic fragments of
      gelsolin. These amyloidogenic fragments deposit systemically, causing a variety
      of symptoms including corneal lattice dystrophy and neurodegeneration. The first
      murine model of the disease recapitulates the aberrant processing of mutant
      plasma gelsolin, amyloid deposition, and the degenerative phenotype. We use what
      we have learned from our biochemical studies, as well as insight from mouse and
      human pathology to propose therapeutic strategies that may halt the progression
      of FAF.

PMID- 22360548
TI  - Intraatrial reentrant circuit in a patient with isomerism of the left atrial
      appendages and atrioventricular septal defect.
AB  - An intraatrial reentrant circuit was identified using an electroanatomical
      mapping system and evaluation of postpacing intervals in a patient with isomerism
      of the left atrial appendages and atrioventricular septal defect. Intraatrial
      reentrant tachycardia was eliminated on the basis of our interpretation of the
      reentry circuit being dependent on a new anatomical obstacle consisting of a
      right-sided atrioventricular annulus and atrial septation patch. We must consider
      the possibility of arrhythmogenic obstacles changing, as a patient grows, long
      after congenital heart disease surgery.

PMID- 22360547
TI  - Sequential allylic C-H amination/vinylic C-H arylation: a strategy for unnatural
      amino acid synthesis from alpha-olefins.
AB  - Tandem reaction sequences that selectively convert multiple C-H bonds of abundant
      hydrocarbon feedstocks to functionalized materials enable rapid buildup of
      molecular complexity in an economical way. A tandem C-H amination/vinylic C-H
      arylation reaction sequence is described under Pd(II)/sulfoxide-catalysis that
      furnishes a wide range of alpha- and beta-homophenylalanine precursors from
      commodity alpha-olefins and readily available aryl boronic acids. General routes
      to enantiopure amino acid esters and densely functionalized homophenylalanine
      derivatives are demonstrated.

PMID- 22360546
TI  - Annual research review: embracing not erasing contextual variability in
      children's behavior--theory and utility in the selection and use of methods and
      informants in developmental psychopathology.
AB  - This paper examines the selection and use of multiple methods and informants for
      the assessment of disruptive behavior syndromes and attention
      deficit/hyperactivity disorder, providing a critical discussion of (a) the
      bidirectional linkages between theoretical models of childhood psychopathology
      and current assessment techniques; and (b) current knowledge concerning the
      utility of different methods and informants for key clinical goals. There is
      growing recognition that children's behavior varies meaningfully across
      situations, and evidence indicates that these differences, in combination with
      informants' unique perspectives, are at least partly responsible for inter-rater
      discrepancies in reports of symptomatology. Such data suggest that we should
      embrace this contextual variability as clinically meaningful information, moving
      away from models of psychopathology as generalized traits that manifest uniformly
      across situations and settings, and toward theoretical conceptualizations that
      explicitly incorporate contextual features, such as considering clinical
      syndromes identified by different informants to be discrete phenomena. We
      highlight different approaches to measurement that embrace contextual variability
      in children's behavior and describe how the use of such tools and techniques may
      yield significant gains clinically (e.g., for treatment planning and monitoring).
      The continued development of a variety of feasible, contextually sensitive
      methods for assessing children's behavior will allow us to determine further the
      validity of incorporating contextual features into models of developmental
      psychopathology and nosological frameworks.

PMID- 22360550
TI  - Characterization of Fasciola samples by ITS of rDNA sequences revealed the
      existence of Fasciola hepatica and Fasciola gigantica in Yunnan Province, China.
AB  - On mainland China, liver flukes of Fasciola spp. (Digenea: Fasciolidae) can cause
      serious acute and chronic morbidity in numerous species of mammals such as sheep,
      goats, cattle, and humans. The objective of the present study was to examine the
      taxonomic identity of Fasciola species in Yunnan province by sequences of the
      first and second internal transcribed spacers (ITS-1 and ITS-2) of nuclear
      ribosomal DNA (rDNA). The ITS rDNA was amplified from 10 samples representing
      Fasciola species in cattle from 2 geographical locations in Yunnan Province, by
      polymerase chain reaction (PCR), and the products were sequenced directly. The
      lengths of the ITS-1 and ITS-2 sequences were 422 and 361-362 base pairs,
      respectively, for all samples sequenced. Using ITS sequences, 2 Fasciola species
      were revealed, namely Fasciola hepatica and Fasciola gigantica. This is the first
      demonstration of F. gigantica in cattle in Yunnan Province, China using a
      molecular approach; our findings have implications for studying the population
      genetic characterization of the Chinese Fasciola species and for the prevention
      and control of Fasciola spp. in this province.

PMID- 22360551
TI  - Proton dynamics in cancer.

PMID- 22360552
TI  - NHE-1: a promising target for novel anti-cancer therapeutics.
AB  - Among the many factors involved in the maintenance of homeostatic growth is the
      tight regulation of cellular pH. Intracellular pH of normal cells is maintained
      within a physiological range thanks to the activity of a number of pH regulators
      that respond to the acidbase shifts associated with normal cellular metabolic
      processes. Interestingly, there is a preponderance of evidence that dysregulation
      of intracellular pH is associated with processes that favor cell transformation
      such as cell cycle progression, enhanced proliferation, insensitivity to growth
      inhibitory stimuli, resistance to apoptosis, genomic instability and
      angiogenesis. Among the strategies employed by the cells to regulate
      intracellular pH, the Na+/H+ exchanger 1 (NHE1) protein from the Na+/H+ exchanger
      (NHE) family has been directly associated with cellular transformation, invasion
      and metastasis. These observations have heightened the interest in NHE1 as a
      promising novel drug target for more effective and selective anti-cancer
      therapeutics. Here we present a review of the basic biology of this remarkable
      protein and present evidence to support targeting NHE1 as a potential anti-cancer
      strategy.

PMID- 22360553
TI  - A rationale for the use of proton pump inhibitors as antineoplastic agents.
AB  - It is becoming increasingly acknowledged that tumorigenesis is not simply
      characterized by the accumulation of rapidly proliferating, genetically mutated
      cells. Microenvironmental biophysical factors like hypoxia and acidity
      dramatically condition cancer cells and act as selective forces for malignant
      cells, adapting through metabolic reprogramming towards aerobic glycolysis.
      Avoiding intracellular accumulation of lactic acid and protons, otherwise
      detrimental to cell survival is crucial for malignant cells to maintain cellular
      pH homeostasis. As a consequence of the upregulated expression and/or function of
      several pH-regulating systems, cancer cells display an alkaline intracellular pH
      (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins,
      proton pumps play an important role in both drug-resistance and metastatic
      spread, thus representing a suitable therapeutic target. Proton pump inhibitors
      (PPI) have been reported as cytotoxic drugs active against several human tumor
      cells and preclinical data have prompted the investigation of PPI as anticancer
      agents in humans. This review will update the current knowledge on the antitumor
      activities of PPI and their potential applications.

PMID- 22360554
TI  - Intracellular proton pumps as targets in chemotherapy: V-ATPases and cancer.
AB  - Cancer cells show a metabolic shift that makes them overproduce protons; this has
      the potential to disturb the cellular acid-base homeostasis. However, these cells
      show cytoplasmic alkalinisation, increased acid extrusion and endosome-dependent
      drug resistance. Vacuolar type ATPases (V-ATPases), together with other
      transporters, are responsible to a great extent for these symptoms. These multi
      subunit proton pumps are involved in the control of cytosolic pH and the
      generation of proton gradients (positive inside) across endocellular membrane
      systems like Golgi, endosomes or lysosomes. In addition, in tumours, they have
      been shown to play an important role in the acidification of the intercellular
      medium. This importance makes them an attractive target to control tumour cell
      proliferation. In the present review we present the major characteristics of this
      kind of proton pumps and we provide some recent insights on their in vivo
      regulation. Also, we review some of the consequences that V-ATPase inhibition
      carries for the tumour cell, such as cell cycle arrest or cell death, and provide
      a brief summary of the studies related to cancer made recently with commercially
      available inhibitors. In the light of recent knowledge on the regulation of this
      proton pump, some new approaches to impair V-ATPase function are also suggested.

PMID- 22360555
TI  - Translational research of photodynamic therapy with acridine orange which targets
      cancer acidity.
AB  - During the past 20 years, we have found that acridine orange (AO) selectively
      accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal
      effects against sarcoma cells in vitro after illumination of the tumor cells with
      visible light or irradiation of the cells with low-dose X-rays. Based on the data
      obtained from basic research, we have employed reduction surgery followed by
      photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with
      musculoskeletal sarcomas, in an attempt to maintain excellent limb function in
      the patients. We have obtained good local control rates and remarkably better
      limb functions with this approach as compared to the results obtained with the
      conventional wide resection surgery. Our basic research demonstrated that AO
      accumulates densely in intracellular acidic vesicles, especially lysosomes, in an
      acidity-dependent manner. In cancer cells that proliferate under hypoxic
      conditions or with Warburg's effect, active glycolysis produces an enormous
      number of protons, which are released by the cells via proton pumps into the
      extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid.
      Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO
      shows marked and prolonged accumulation in the acidic lysosomes of cancer cells.
      Photon energy excites the AO resulting in the production of activated oxygen
      species, which oxidize the fatty acids of the lysosomal membrane, resulting in
      the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer
      cells. Based on these observations, we conclude that AO-PDT & RDT target acidic
      vesicles, especially the lysosomes, in cancer cells, to exhibit selective anti
      cancer cell activity. Therefore, it is suggested that AO excited by photon energy
      has excellent potential as an anticancer "Magic Bullet".

PMID- 22360556
TI  - Resveratrol in cancer: cellular and mitochondrial consequences of proton
      transport inhibition.
AB  - Transformed cells suffer several changes leading to the increase of protective
      mechanisms and show a metabolic profile in accordance with higher proliferative
      capacity. In these mechanisms, changes in mitochondrial activity cause a higher
      glycolytic metabolism in detriment of oxidative phosphorylation. In these
      changes, H+-ATPase regulation seems to be importantly involved. During the last
      years, polyphenols and specially the stilbene resveratrol and related members of
      its family have been studied because they are able to affect tumour cell growth
      and cancer progression. Among the different effects induced by resveratrol,
      inhibition of H+-ATPase seems to be one important mechanism in its effect on
      cancer progression. Further, an ectopic H+-ATPase located in the outer surface of
      plasma membrane has been recently involved in cancer progression and
      angiogenesis. In this article we review the latest findings about resveratrol
      inhibition of H+-ATPase and its importance in tumour cell growth and cancer
      progression.

PMID- 22360557
TI  - Physiology, pharmacology and pathophysiology of the pH regulatory transport
      proteins NHE1 and NBCn1: similarities, differences, and implications for cancer
      therapy.
AB  - The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+,HCO3-
      cotransporter NBCn1 (SLC4A7) are coexpressed in a wide range of tissues. Under
      normal physiological conditions these transporters play an ostensibly similar
      role, namely that of net acid extrusion after cellular acidification. In
      addition, they have been implicated in multiple other cellular processes,
      including regulation of transepithelial transport, cell volume, cell
      death/survival balance, and cell motility. In spite of their apparent functional
      similarity, the two transporters also serve distinctly different functions and
      are differentially regulated. Here, we provide an update on the basic structure,
      function, regulation, physiology and pharmacology of NHE1 and NBCn1, with
      particular focus on the factors responsible for their functional similarities and
      differences. Finally, we highlight recent findings implicating these transporters
      in cancer development, and discuss issues relating to NHE1 and NBCn1 as potential
      targets in cancer treatment.

PMID- 22360558
TI  - Multiple biological activities of lactic acid in cancer: influences on tumor
      growth, angiogenesis and metastasis.
AB  - High rate of glycolysis is a metabolic hallmark of cancer. While anaerobic
      glycolysis promotes energy production under hypoxia, aerobic glycolysis, the
      Warburg effect, offers a proliferative advantage through redirecting carbohydrate
      fluxes from energy production to biosynthetic pathways. To fulfill tumor cell
      needs, the glycolytic switch is associated with elevated glucose uptake and
      lactic acid release. Altered glucose metabolism is the basis of positron emission
      tomography using the glucose analogue tracer [18F]- fluorodeoxyglucose, a widely
      used clinical application for tumor diagnosis and monitoring. On the other hand,
      high levels of lactate have been associated with poor clinical outcome in several
      types of human cancers. Although lactic acid was initially considered merely as
      an indicator of the glycolytic flux, many evidences originally from the study of
      normal tissue physiology and more recently transposed to the tumor situation
      indicate that lactic acid, i.e. the lactate anion and protons, directly
      contributes to tumor growth and progression. Here, we briefly review the current
      knowledge pertaining to lactic acidosis and metastasis, lactate shuttles, the
      influence of lactate on redox homeostasis, lactate signaling and lactate-induced
      angiogenesis in the cancer context. The monocarboxylate transporters MCT1 and
      MCT4 have now been confirmed as prominent facilitators of lactate exchanges
      between cancer cells with different metabolic behaviors and between cancer and
      stromal cells. We therefore address the function and regulation of MCTs,
      highlighting MCT1 as a novel anticancer target. MCT1 inhibition allows to
      simultaneously disrupt metabolic cooperativity and angiogenesis in cancer with a
      same agent, opening a new path for novel anticancer therapies.

PMID- 22360559
TI  - Inhibition of V-ATPase and carbonic anhydrases as interference strategy with
      tumor acidification processes.
AB  - Two of the key proteins involved in tumor acidification are the V-ATPase and the
      tumor-associated carbonic anhydrases (CAs), such as CA IX and XII. Although there
      are many chemical classes of V-ATPase inhibitors, most of them are toxic for
      mammals and their potential use as antitumor drugs is limited. The proton pump
      inhibitors (PPIs), a class of antiulcer agents in clinical use for more than 30
      years, have been proven to be useful in modulating tumor acidification,
      presumably by inactivating V-ATPase, through modification of Cys residues
      essential for the catalytic activity of the ATPase. This mechanism of action has
      yet to be demonstrated, but several recent clinical trials showed the efficacity
      of this approach for inhibiting the growth of tumors and their re-sensitivization
      to anticancer drugs such as cisplatin, or doxorubicin. Further studies are anyhow
      warranted to better understand the role of PPIs in the management of cancer. The
      monoclonal antibodies (mAbs) girentuximab, and its 124I -radiolabelled variant
      targeting CA IX are in advanced clinical trials both for the treatment and
      imaging of hypoxic tumors overexpressing CA IX. Small molecule CA IX inhibitors,
      of sulfonamide and coumarin type are in advanced preclinical evaluation, both for
      imaging and treatment of solid tumors and metastases in which CA IX/XII are
      present. As cancer is still a big clinical problem and most of the hypoxic tumors
      do not respond to classical anticancer drugs or to radiotherapy, the development
      of alternative anticancer approaches, such as interference with tumor
      acidification through inhibition of VATPase and CAs, represents an interesting
      avenue for future research.

PMID- 22360560
TI  - Acid-extrusion from tissue: the interplay between membrane transporters and pH
      buffers.
AB  - The acid-base balance of cells is related to the concentration of free H+ ions.
      These are highly reactive, and their intracellular concentration must be
      regulated to avoid detrimental effects to the cell. H+ ion dynamics are
      influenced by binding to chelator substances ('buffering'), and by the
      production, diffusion and membrane-transport of free H+ ions or of the H+-bound
      chelators. Intracellular pH (pHi) regulation aims to balance this system of
      diffusion-reaction-transport processes at a favourable steady-state pHi. The
      ability of cells to regulate pHi may set a limit to tissue growth and can be
      subject to selection pressures. Cancer cells have been postulated to respond
      favourably to such selection pressures by evolving a better means of pHi
      regulation. A particularly important feature of tumour pHi regulation is acid
      extrusion, which involves H+-extrusion and HCO3--uptake by membrane-bound
      transporter-proteins. Extracellular CO2/HCO3- buffer facilitates these membrane
      transport processes. As a mobile pH-buffer, CO2/HCO3- protects the extracellular
      space from excessive acidification that could otherwise inhibit further acid
      extrusion. CO2/HCO3- also provides substrate for HCO3--transporters. However, the
      inherently slow reaction kinetics of CO2/HCO3- can be rate-limiting for acid
      extrusion. To circumvent this, cells can express extracellular-facing carbonic
      anhydrase enzymes to accelerate the attainment of equilibrium between CO2, HCO3-
      and H+. The acid-extrusion apparatus has been proposed as a target for anti
      cancer therapy. The major targets include H+ pumps, Na+/H+ exchangers and
      carbonic anhydrases. The effectiveness of such therapy will depend on the correct
      identification of rate-limiting steps in pHi regulation in a specific type of
      cancer.

PMID- 22360561
TI  - Bifunctional PAMAM dendrimer conjugates of folic acid and methotrexate with
      defined ratio.
AB  - Our group previously developed a multifunctional, targeted cancer therapeutic
      based on Generation 5 (G5) polyamidoamine (PAMAM) dendrimers. In those studies we
      conjugated the targeting molecule folic acid (FA) and the chemotherapeutic drug
      methotrexate (MTX) sequentially. This complex macromolecule was shown to
      selectively bind and kill KB tumor cells that overexpress folate receptor (FR) in
      vitro and in vivo. However, the multistep conjugation strategy employed in the
      synthesis of the molecule resulted in heterogeneous populations having differing
      numbers and ratios of the functionally antagonistic FA and MTX. This led to
      inconsistent and sometimes biologically inactive batches of molecules, especially
      during large-scale synthesis. We here resolved this issue by using a novel
      triazine scaffold approach that reduces the number of dendrimer conjugation steps
      required and allows for the synthesis of G5 conjugates with defined ratios of FA
      and MTX. Although an unoccupied gamma-glutamyl carboxylate of FA has been
      previously suggested to be nonessential for FR binding, the functional
      requirement of an open alpha-carboxylate still remains unclear. In an attempt to
      also address this question, we have synthesized isomeric FA dendrimer conjugates
      (alpha-carboxyl or gamma-carboxyl linked). Competitive binding studies revealed
      that both linkages have virtually identical affinity toward FR on KB cells. Our
      studies show that a novel bifunctional triazine-based conjugate G5-Triazine
      gammaMTX-alphaFA with identical numbers of FA and MTX binds to FR through a
      polyvalent interaction and induces cytotoxicity in KB cells through FR-mediated
      cellular internalization, inducing higher toxicity as compared to conjugates
      synthesized by the multistep strategy. This work serves as a proof of concept for
      the development of bifunctional dendrimer conjugates that require a defined ratio
      of two functional molecules.

PMID- 22360562
TI  - Intramedullary recurrence of germinoma in the spinal cord 15 years after complete
      remission of a pineal lesion.
AB  - The authors present a case of germinoma that was initially found in the pineal
      region and recurred 15 years later in the intramedullary cervical spinal cord
      after intensive chemo- and radiotherapy and diagnosis of complete remission.  
      This 28-year-old man initially presented with seizures. Hydrocephalus and a
      pineal tumor were found on radiological examination, and partial resection of the
      tumor was performed. Histological diagnosis showed a pure germinoma. Following
      surgery, the patient received a combination of chemo- and radiotherapy, and a
      complete remission was shown. However, after 15 years of follow-up, he presented
      with gait disturbances. Spinal MRI showed an intramedullary mass lesion in the
      cervical spinal cord. The cervical lesion was biopsied, and histological
      examination again revealed a pure germinoma.   With germinomas, the possibility
      of a drop metastasis from an intracranial lesion to the spinal cord must be
      considered during follow-up. However, in the present case, analysis of a CSF
      sample showed no abnormalities as in previously published cases. In recent years,
      multidisciplinary treatments have demonstrated good event-free survival rates in
      cases of pure germinomas, but long-term outcomes over the decades are not fully
      known. Continual follow-up of such cases is recommended even after complete
      remission has been achieved.

PMID- 22360563
TI  - Spinal and paraspinal giant cervical cavernous malformation with postpartum
      presentation.
AB  - Cavernous malformations (CMs) are found throughout the CNS but are relatively
      uncommon in the spine. In this report, the authors describe a giant CM with the
      imaging appearance of an aggressive, invasive, expansive tumor in the cervical
      spine. The intradural extramedullary portion of the tumor originated from a
      cervical nerve root; histologically, the lesion was identified as an intraneural
      CM. Most of the tumor extended into the paraspinal tissues. The tumor was also
      epidural, intraosseous, and osteolytic and had completely encased cervical nerve
      roots, peripheral nerves, branches of the brachial plexus, and the vertebral
      artery on the right side. It became symptomatic during the puerperal period.
      Gross-total resection was achieved using staged operative procedures, complex
      dural reconstruction, spinal fixation, and fusion. Clinical, radiographic, and
      histological details, as well as a discussion of the relevant literature, are
      provided.

PMID- 22360564
TI  - Symposium on zwitterionic surfactants: preface.

PMID- 22360566
TI  - An Australian perspective.
AB  - Discussing the future of UK clinical pharmacology, eight Australasian clinical
      pharmacologists emphasized the need to make the discipline 'indispensable' in key
      areas. The visibility of clinical pharmacology in Australasia has been improved
      by working with the Consumers' Health Forum in Australia in the construction of
      the national Policy on Quality Use of Medicines and, later, of the formal
      National Medicines Policy. Our expertise in clinical pharmacology, combined with
      the Health Forum's political skills, proved a potent force for launching these
      policies. A second example was the construction of the national prescribing
      curriculum in partnership with the National Prescribing Service. This is being
      used in all medical schools with senior students. At a local level we found that
      taking over clinical toxicology services (that other clinicians wanted to
      jettison) provided a stimulus to clinical research and later the formation of a
      productive subgroup to study the special problems of envenomation. Fourthly, we
      note that no clinical pharmacology unit in UK is designated as a WHO
      collaborating centre. Considerable difference can be made to national problems
      with medicines by clinical pharmacologists willing to work for periods within
      developing countries. This has given a greater profile to several groups in
      Australia. The principle of stepping out of conventional settings and actively
      seeking collaboration with other groups beyond our discipline has enhanced the
      profile of the discipline in Australasia and could do the same in the UK.

PMID- 22360565
TI  - Rapid assembly of a library of lipophilic iminosugars via the thiol-ene reaction
      yields promising pharmacological chaperones for the treatment of Gaucher disease.
AB  - A highly divergent route to lipophilic iminosugars that utilizes the thiol-ene
      reaction was developed to enable the rapid synthesis of a collection of 16
      dideoxyiminoxylitols bearing various different lipophilic substituents. Enzyme
      kinetic analyses revealed that a number of these products are potent, low
      nanomolar inhibitors of human glucocerebrosidase that stabilize the enzyme to
      thermal denaturation by up to 20 K. Cell based assays conducted on Gaucher
      disease patient derived fibroblasts demonstrated that administration of the
      compounds can increase lysosomal glucocerebrosidase activity levels by
      therapeutically relevant amounts, as much as 3.2-fold in cells homozygous for the
      p.N370S mutation and 1.4-fold in cells homozygous for the p.L444P mutation.
      Several compounds elicited this increase in enzyme activity over a relatively
      wide dosage range. The data assembled here illustrate how the lipophilic moiety
      common to many glucocerebrosidase inhibitors might be used to optimize a lead
      compound's ability to chaperone the protein in cellulo. The flexibility of this
      synthetic strategy makes it an attractive approach to the rapid optimization of
      glycosidase inhibitor potency and pharmacokinetic behavior.

PMID- 22360567
TI  - The development of satisfaction with service-related choices for disabled young
      people with degenerative conditions: evidence from parents' accounts.
AB  - Satisfaction with service-related choices has not received much research
      attention, especially beyond medical/health-related decisions. This paper reports
      findings from an analysis of parents' accounts of making service-related choices
      with, or on behalf of, a disabled son or daughter with a degenerative condition.
      It focuses particularly on factors and processes, which contribute to parents'
      satisfaction. This is particularly interesting given that sub-optimal outcomes or
      negative consequences are often experienced following a service-related choice
      being implemented. The data reported here were collected as part of a larger,
      longitudinal study (the Choice and Change project) of service users' experiences
      of choice-making, including the outcomes and consequences of those choices.
      Parents of disabled young people with degenerative conditions formed part of this
      sample. The accounts of 14 of these parents, collected over three interviews
      during a two and a half-year period, all of whom expressed satisfaction with the
      medium- to long-term outcomes of a service-related choice, were selected for
      specific analyses to understand what underlies satisfaction with service-related
      choices. Clarity of the desired outcome for the young person supported effective
      decision-making and led parents to feel confident that the best possible choice
      was being made. Evidence of desired outcomes being attained were used by parents
      to 'trade off' the negative consequences of a choice. These included the
      considerable demands placed on parents' personal, financial and practical
      resources to operationalise a choice, and the emotional impact incurred by
      significant changes such as the loss of the carer role. The passage of time was
      important in allowing evidence of positive outcomes to emerge, psychological or
      emotional adjustments to be made, and for parents to develop trust in new service
      providers. The findings suggest that practitioners can have an important role in
      both practical and emotional support for parents' choice-making for, or with,
      their disabled son/daughter.

PMID- 22360568
TI  - Magnetosomes eliminate intracellular reactive oxygen species in Magnetospirillum
      gryphiswaldense MSR-1.
AB  - Magnetotactic bacteria synthesize magnetic particles called magnetosomes that
      cause them to orient to their external magnetic fields. However, the
      physiological significance and other possible functions of these magnetosomes
      have not been explored in detail. In this study, we have investigated the
      biological functions of magnetosomes with respect to their ability to scavenge
      reactive oxygen species (ROS) in Magnetospirillum gryphiswaldense MSR-1. To
      assess the changes in ROS levels under different conditions, cells were cultured
      under aerobic or micro-aerobic conditions in medium containing high and low
      amounts of iron. To ensure that the observed results were not due to nonspecific
      interactions, reactions were carried out using a mutant deficient in synthesizing
      magnetite (mamO-deficient mutant), its complementary strain or the wild-type MSR
      1. We observed that the levels of intercellular ROS under micro-aerobic
      conditions with high-iron medium were much higher when the non-synthetic Fe(3)
      O(4)  crystals mutant Mu21-415 was employed for the assay, compared with the wild
      type or complementary strain, or when conditions were aerobic with low-iron
      medium. These results indicated that magnetosomes function in the scavenging of
      intracellular ROS. Furthermore, we have demonstrated that the magnetosomes
      exhibit peroxidase-like properties, by using the earlier reported in vitro
      horseradish peroxidase assay for artificial magnetic nanoparticles. In addition
      to possessing peroxidase-like activity, the magnetosomes also exhibited a more
      enzymatic kinetic response, suggesting that proteins on the membranes of the
      magnetosomes likely contribute to the enzymatic activity. This is the first study
      to demonstrate that magnetosomes play an important role in decreasing or
      eliminating ROS.

PMID- 22360569
TI  - Electrochemical, computational, and photophysical characterization of new
      luminescent dirhenium-pyridazine complexes containing bridging OR or SR anions.
AB  - A series of [Re(2)(MU-ER)(2)(CO)(6)(MU-pydz)] complexes have been synthesized (E
      = S, R = C(6)H(5), 2; E = O, R = C(6)F(5), 3; C(6)H(5), 4;  CH(3), and 5; H, 6),
      starting either from [Re(CO)(5)O(3)SCF(3)] (for 2 and 4), [Re(2)(MU
      OR)(3)(CO)(6)](-) (for 3 and 5), or [Re(4)(MU(3)-OH)(4)(CO)(12)] (for 6). Single
      crystal diffractometric analysis showed that the two MU-phenolato derivatives (3
      and 4) possess an idealized C(2) symmetry, while the MU-benzenethiolato
      derivative (2) is asymmetrical, because of the different conformation adopted by
      the phenyl groups. A combined density functional and time-dependent density
      functional study of the geometry and electronic structure of the complexes showed
      that the lowest unoccupied molecular orbital (LUMO) and LUMO+1 are the two lowest
      lying pi* orbitals of pyridazine, whereas the highest occupied molecular orbitals
      (HOMOs) are mainly constituted by the "t(2g)" set of the Re atoms, with a strong
      Re-(MU-E) pi* character. The absorption spectra have been satisfactorily
      simulated, by computing the lowest singlet excitation energies. All the complexes
      exhibit one reversible monoelectronic reduction centered on the pyridazine ligand
      (ranging from -1.35 V to -1.53 V vs Fc(+)|Fc). The benzenethiolato derivative 2
      exhibits one reversible two-electron oxidation (at 0.47 V), whereas the OR
      derivatives show two close monoelectronic oxidation peaks (ranging from 0.85 V to
      1.35 V for the first peak). The thioderivative 2 exhibits a very small
      electrochemical energy gap (1.9 eV, vs 2.38-2.70 eV for the OR derivatives), and
      it does not show any photoluminescence. The complexes containing OR ligands show
      from moderate to poor photoluminescence, in the range of 608-708 nm, with quantum
      yields decreasing (ranging from 5.5% to 0.07%) and lifetimes decreasing (ranging
      from 550 ns to 9 ns) (3 > 4 > 6 ~ 5) with increasing emission wavelength. The
      best emitting properties, which are closely comparable to those of the dichloro
      complex (1), are exhibited by the pentafluorophenolato derivative (3).

PMID- 22360570
TI  - The PP1 binding code: a molecular-lego strategy that governs specificity.
AB  - Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly
      200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are
      ubiquitously expressed but show an exceptional diversity in brain, testis and
      white blood cells. The binding of PIPs is mainly mediated by short motifs that
      dock to surface grooves of PP1. Although PIPs often contain variants of the same
      PP1 binding motifs, they differ in the number and combination of docking sites.
      This molecular-lego strategy for binding to PP1 creates holoenzymes with unique
      properties. The PP1 binding code can be described as specific, universal,
      degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference
      with substrate recruitment or access to the active site. In addition, some PIPs
      have a subcellular targeting domain that promotes dephosphorylation by increasing
      the local concentration of PP1. The diversity of the PP1 interactome and the
      properties of the PP1 binding code account for the exquisite specificity of PP1
      in vivo.

PMID- 22360571
TI  - The branching pattern of the middle cerebral artery: is the intermediate trunk
      real or not? An anatomical study correlating with simple angiography.
AB  - OBJECT: The branching structure of the middle cerebral artery (MCA) remains a
      debated issue. In this study the authors aimed to describe this branching
      structure in detail. METHODS: Twenty-seven fresh, human brains (54 hemispheres)
      obtained from routine autopsies were used. The cerebral arteries were first
      filled with colored latex and contrast agent, followed by fixation with
      formaldehyde. All dissections were done under a microscope. During examination,
      the trunk structures of the MCA and their relations with cortical branches were
      demonstrated. Lateral radiographs of the same hemispheres were then obtained and
      comparisons were made. Angles between the MCA trunks were measured on 3D CT
      cerebral angiography images in 25 patients (50 hemispheres), and their
      correlations with the angles obtained in the cadaver brains were evaluated.
      RESULTS: A new classification was made in relation to the terminology of the
      intermediate trunk, which is still a subject of debate. The intermediate trunk
      was present in 61% of cadavers and originated from a superior trunk in 55% and
      from an inferior trunk in 45%. Cortical branches supplying the motor cortex
      (precentral, central, and postcentral arteries) significantly originated from the
      intermediate trunk, and the diameter of the intermediate trunk significantly
      increased when it originated from the superior trunk. In measurements of the
      angles between the superior and intermediate trunks, it was found that the
      intermediate trunk had significant dominance in supplying the motor cortex as the
      angle increased. The intermediate trunk was classified into 3 types based on the
      angle values and the distance to the bifurcation point as Group A
      (pseudotrifurcation type), Group B (proximal type), and Group C (distal type).
      Group A trunks were seemingly closer to the trifurcation structure that has been
      reported on in the literature and was seen in 15%. Group B trunks were the most
      common type (55%), and Group C trunks were characterized as the farthest from the
      bifurcation point. Group C trunks also had the smallest diameter and fewest
      cortical branches. Similarities were found between the angles in cadaver
      specimens and on 3D CT cerebral angiography images. Beyond the separation point
      of the MCA, trunk structures always included the superior trunk and inferior
      trunk, and sometimes the intermediate trunk. CONCLUSIONS: Interrelations of these
      vascular structures and their influences on the cortical branches originating
      from them are clinically important. The information presented in this study will
      ensure reliable diagnostic approaches and safer surgical interventions,
      particularly with MCA selective angiography.

PMID- 22360572
TI  - Staged resection of large vestibular schwannomas.
AB  - OBJECT: Staged resection of large vestibular schwannomas (VSs) has been proposed
      as a strategy to improve facial nerve outcomes and morbidity. The authors report
      their experience with 2-stage resections of large VSs and analyze the
      indications, facial nerve outcomes, surgical results, and complications. The
      authors compare these results with those of a similar cohort of patients who
      underwent a single-stage resection. METHODS: A retrospective review of all
      patients (age > 18 years) who underwent surgery from 2002 to 2010 for large (>= 3
      cm) VSs at the authors' institution with a minimum of 6 months follow-up was
      undertaken. A first-stage retrosigmoid approach (without meatal drilling) was
      performed to remove the cerebellopontine angle portion of the tumor and to
      decompress the brainstem. A decision to stage the operation was made
      intraoperatively if there was cerebellar or brainstem edema, excessive tumor
      adherence to the facial nerve or brainstem, a poorly stimulating facial nerve, or
      a thinned or splayed facial nerve. A second-stage translabyrinthine approach was
      performed at a later date to remove the remaining tumor. The single-stage
      resection consisted of a retrosigmoid approach with meatal drilling. Patient
      charts were evaluated for tumor size, extent of resection, tumor recurrence,
      House-Brackmann facial nerve function grade, and complications. RESULTS: Twenty
      eight and 19 patients underwent 2- or single-stage resection of a large VS,
      respectively. The average tumor size was 3.9 cm (range 3.2-7 cm) in the 2-stage
      group and 3.9 cm (range 3.1-5 cm) in the single-stage group. The mean follow-up
      was 36 +/- 19 months in the 2-stage group versus 24 +/- 14 months in the single
      stage group. Gross-total or near-total resection was achieved in 27 (96.4%) of 28
      patients in the 2-stage group and 15 (79%) of 19 patients in the single-stage
      group (p < 0.01). Anatomical facial nerve preservation was achieved in all but 1
      patient (94.7%), and there were no recurrences on follow-up imaging in the 2
      stage group. Good facial nerve functional outcome (House-Brackmann Grades I and
      II) at last follow-up was achieved in 23 (82%) of 28 patients in the 2-stage
      group and 10 (53%) of 19 patients in the single-stage group (p < 0.01).
      Cerebrospinal fluid leak-related complications (intracranial hypotension, blood
      patch, and lumboperitoneal shunt for pseudomeningocele) were more common in the 2
      stage group. There were no postoperative strokes, hemorrhages, or deaths in
      either group. CONCLUSIONS: The authors' results suggest that staged resection of
      large VSs may potentially achieve better facial nerve outcomes. There does not
      appear to be added neurological morbidity with staged resections.

PMID- 22360573
TI  - Pituitary adenoma identification.

PMID- 22360574
TI  - Indocyanine green fluorescence endoscopy for visual differentiation of pituitary
      tumor from surrounding structures.
AB  - OBJECT: As demonstrated by histological and neuroimaging studies, pituitary
      adenomas have a capillary vascular density that differs significantly from that
      of surrounding structures. The authors hypothesized that intraoperative
      indocyanine green (ICG) fluorescence endoscopy could be used to visually
      differentiate tumor from surrounding tissues, including normal pituitary gland
      and dura. METHODS: After institutional review board approval, 16 patients
      undergoing endoscopic transsphenoidal surgery for benign pituitary lesions were
      prospectively enrolled in the study. A standard endoscopic endonasal approach to
      the sella was completed. Each patient then underwent endoscopic examination of
      the sellar dura and then the exposed pituitary adenoma after ICG bolus injection
      (12.5-25 mg). This examination was performed using a custom endoscope with a near
      infrared light source and excitation wavelength filter. RESULTS: The authors
      successfully recorded ICG fluorescence from sellar dura, pituitary, and
      surrounding structures in 12 of 16 patients enrolled. There were 3 technical
      failures of intraoperative ICG endoscopy, and 1 patient was excluded following
      discovery of a dye cross-allergy. A standard dose of 25 mg of ICG in 10 ml of
      aqueous solution optimized visualization of sellar region microvasculature within
      45 seconds of peripheral bolus injection. Adenoma was less fluorescent than
      normal pituitary gland. Dural invasion by tumor was identifiable by a marked
      increase in fluorescence compared with native dura. The ICG endoscopic
      examination added 15-20 minutes of operative time under general anesthesia. There
      were no complications that resulted from use of ICG or the fluorescent light
      source. CONCLUSIONS: Indocyanine green fluorescence endoscopy shows promise as an
      intraoperative modality to visually distinguish pituitary tumors from normal
      tissue and to visually identify areas of dural invasion, thereby facilitating
      complete tumor resection and minimizing injury to surrounding structures. These
      results support the continued development of fluorescence endoscopic resection
      techniques.

PMID- 22360575
TI  - Treatment of acute bronchitis with EPs 7630: randomized, controlled trial in
      children and adolescents.
AB  - BACKGROUND: The aim of this trial was to investigate the efficacy and
      tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides, in
      children and adolescents suffering from acute bronchitis, outside the strict
      indication for antibiotics. METHODS: A total of 220 patients with acute
      bronchitis were randomized and given either verum containing EPs 7630 (1-6
      years/>6-12 years/>12-18 years: 3 * 10/3 * 20/3 * 30 drops/day) or matching
      placebo for 7 days. The main outcome measure was the change in the total score of
      bronchitis-specific symptoms (BSS) from day 0 to day 7. RESULTS: The decrease in
      the BSS total score was significantly higher for EPs 7630 compared to placebo
      (change day 0-day 7: 4.4 +/- 1.6 vs 2.9 +/- 1.4 points; P < 0.0001). Improvements
      were most pronounced for 'coughing' and 'rales at auscultation'. Tolerability was
      similarly good in both groups. CONCLUSIONS: EPs 7630 proved to be an efficacious
      and well-tolerated option for the treatment of acute bronchitis in children and
      adolescents outside the strict indication for antibiotics.

PMID- 22360576
TI  - Hydroxycarbamide alters erythroid gene expression in children with sickle cell
      anaemia.
AB  - Sickle cell anaemia (SCA) is a severe debilitating haematological disorder
      associated with a high degree of morbidity and mortality. The level of fetal
      haemoglobin (HbF) is well-recognized as a critical laboratory parameter: lower
      HbF is associated with a higher risk of vaso-occlusive complications, organ
      damage, and early death. Hydroxycarbamide treatment can induce HbF, improve
      laboratory parameters, and ameliorate clinical complications of SCA but its
      mechanisms of action remain incompletely defined and the HbF response is highly
      variable. To identify pathways of hydroxycarbamide activity, we performed
      microarray expression analyses of early reticulocyte RNA obtained from children
      with SCA enrolled in the HydroxyUrea Study of Long-term Effects (NCT00305175) and
      examined the effects of hydroxycarbamide exposure in vivo. Hydroxycarbamide
      affected a large number of erythroid genes, with significant decreases in the
      expression of genes involved in translation, ribosome assembly and chromosome
      organization, presumably reflecting the daily cytotoxic pulses of
      hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes
      associated with HbF including BCL11A, a key regulator of baseline HbF levels.
      Together, these data indicate that hydroxycarbamide treatment for SCA leads to
      substantial changes in erythroid gene expression, including BCL11A and other
      potential signalling pathways associated with HbF induction.

PMID- 22360577
TI  - Lung transplantation in patients with coal workers' pneumoconiosis.
AB  - Patients with coal workers' pneumoconiosis (CWP) can develop chronic respiratory
      failure and require lung transplantation. A retrospective review was performed of
      the 712 referrals and 143 patients undergoing unilateral or bilateral lung
      transplantation at the University of Kentucky Medical Center between January 1999
      and July 2009. Twenty-one of the 712 referrals (3%) had a diagnosis of CWP with
      eight patients eventually undergoing lung transplant (six single, two bilateral).
      The mean age of the cohort was 53 +/- 5 (mean +/- SD) yr (range 45-59). There was
      no increased risk of perioperative or postoperative complications. Six patients
      (75%) remain alive after a mean follow-up of 1013 +/- 857 d with the two deaths
      attributable to sepsis 683 and 145 d after transplant, respectively. There were
      no pulmonary complications because of the native lung in patients after a single
      lung transplant, with otherwise good clinical outcomes seen after lung
      transplantation.

PMID- 22360578
TI  - An improved procedure for low-temperature embedding of high-pressure frozen and
      freeze-substituted plant tissues resulting in excellent structural preservation
      and contrast.
AB  - Here we describe refinements in the processing of high-pressure frozen samples of
      delicate plant tissues for immuno-electron microscopy. These involve: shortened
      freeze-substitution schedules, lower temperatures during processing and
      polymerisation, the avoidance of temperature fluctuations and the optimisation of
      heat transfer from the specimens using small disposable aluminium containers. The
      application of these modifications leads to very good structural preservation and
      selective membrane contrast. As a result, the versatility of the method is
      increased since not only immuno-electron microscopical studies can be performed
      but often the quality is also quite suitable for structural investigations.

PMID- 22360579
TI  - Growth of isotropic domains as a mechanism of dynamic diffraction grating
      recording in low molecular liquid-crystalline derivatives of azobenzene.
AB  - In this paper, we propose and explain the mechanism of dynamic molecular motions
      and isotropic domain formation during the diffraction grating recording in low
      molecular liquid-crystalline azobenzene derivatives. The photochromic molecules
      of 4-heptyl-4'-methoxyazobenzene, showing nematic liquid-crystalline properties
      close to the room temperature (from T = 34  degrees C), are used. A one
      dimensional model of the grating formation is formulated based on in vivo
      polarized microscope observations. Formation and growth of the isotropic domains
      induced by the sinusoidally modulated Gaussian light intensity distribution is
      proposed as the mechanism and is used for experimental data fitting. The
      influence of the recording light intensity, grating period, and temperature on
      the domain growth rate factor is checked.

PMID- 22360580
TI  - Perspectives of immunization program managers on 2009-10 H1N1 vaccination in the
      United States: a national survey.
AB  - In June and July 2010, we conducted a national internet-based survey of 64 city,
      state, and territorial immunization program managers (IPMs) to assess their
      experiences in managing the 2009-10 H1N1 influenza vaccination campaign. Fifty
      four (84%) of the managers or individuals responsible for an immunization program
      responded to the survey. To manage the campaign, 76% indicated their health
      department activated an incident command system (ICS) and 49% used an emergency
      operations center (EOC). Forty percent indicated they shared the leadership of
      the campaign with their state-level emergency preparedness program. The managers'
      perceptions of the helpfulness of the emergency preparedness staff was higher
      when they had collaborated with the emergency preparedness program on actual or
      simulated mass vaccination events within the previous 2 years. Fifty-seven
      percent found their pandemic influenza plan helpful, and those programs that
      mandated that vaccine providers enter data into their jurisdiction's immunization
      information system (IIS) were more likely than those who did not mandate data
      entry to rate their IIS as valuable for facilitating registration of
      nontraditional providers (42% vs. 25%, p<0.05) and tracking recalled influenza
      vaccine (50% vs. 38%, p<0.05). Results suggest that ICS and EOC structures,
      pandemic influenza plans, collaborations with emergency preparedness partners
      during nonemergencies, and expanded use of IIS can enhance immunization programs'
      ability to successfully manage a large-scale vaccination campaign. Maintaining
      the close working relationships developed between state-level immunization and
      emergency preparedness programs during the H1N1 influenza vaccination campaign
      will be especially important as states prepare for budget cuts in the coming
      years.

PMID- 22360582
TI  - The impact of arteriovenous fistula creation in pulmonary hypertension:
      measurement of pulmonary pressures by right heart catheterization in a patient
      with respiratory failure following arteriovenous fistula creation.
AB  - Pulmonary hypertension (PHT) is frequent in patients receiving hemodialysis (HD)
      and carries a high mortality. While it has been suggested that arteriovenous
      fistulae (AVF) may exacerbate PHT in HD patients, it has also been observed that
      creating AVF in patients with chronic lung disease and normal renal function may
      lead to improved exercise tolerance. Most of the observations regarding HD
      patients using echocardiography demonstrated that temporary closure of AVF
      improved pulmonary pressures. We present the case of a 45-year-old patient with
      chronic obstructive pulmonary disease on HD who experienced respiratory failure
      following AVF formation and underwent right heart catheterization. Severe PHT was
      diagnosed but transient occlusion of the fistula failed to improve the PHT. This
      case supports the theory that fistula creation does not exacerbate pre-existing
      PHT and that AVF can be the access of choice in patients with known chronic lung
      disease and pulmonary hypertension.

PMID- 22360583
TI  - Phototherapy causes a transient DNA damage in jaundiced newborns.
AB  - In this study, we aimed to clarify the following questions: 1) Does phototherapy
      (PT) cause genotoxicity in full-term newborn babies undergoing PT as a result of
      neonatal jaundice?, 2) if genotoxic effect occurs, is there any relationship
      between the duration of PT and genotoxicity?, and 3) is genotoxic effect
      temporary or not? The frequency of sister chromatid exchange (SCE) was determined
      in jaundiced newborns before, during, and after phototherapy, then determined
      again in childhood (approximately 3.5 years old). Mean frequency of SCE of 22
      full-term jaundiced babies significantly increased during the PT procedure and in
      every single day, compared to the previous day, in comparison to the pre-PT basal
      value (6.20 +/- 0.57;); mean SCE frequencies at 24, 48, 72, and 96 hours were
      7.75 +/- 0.40, 8.16 +/- 0.47, 8.50 +/- 0.40, and 9.36 +/- 0.55, respectively (all
      P-values <0.01). In childhood, no significant difference was found between the
      mean SCE value (4.9 +/- 0.9) of 20 of 22 children, who received PT in the
      neonatal period, and the mean SCE value (4.7 +/- 0.6) of 20 coevaluated healthy
      children (P = 0.40). This study demonstrates that the negative effect of PT on
      SCE is a temporary effect.

PMID- 22360584
TI  - Novel intramolecular photocyclization of alpha-arylthiophene derivatives.
AB  - Photoirradiation of alpha-arylthiophene derivatives linked with an alkene moiety
      through a three-atom spacer gave unprecedented cyclobutene-fused
      perhydrothiapentalene-type compounds in high yields, but neither [2 + 2] nor [4 +
      2] cycloaddition products. The reaction afforded a single diastereomer in many
      cases. The chemical structure and relative configuration of a typical product
      were unambiguously determined by X-ray crystallographic analysis.

PMID- 22360585
TI  - Photoinduced RNA interference.
AB  - Because RNA interference (RNAi) can be applied to any gene, this technique has
      been widely used for studying gene functions. In addition, many researchers are
      attempting to use RNAi technology in RNAi-based therapies. However, several
      challenging and controversial issues have arisen during the widespread
      application of RNAi including target gene specificity, target cell specificity,
      and spatiotemporal control of gene silencing. To address these issues, several
      groups have utilized photochemistry to control the RNA release, both spatially
      and temporally. In this Account, we focus on recent studies using photocleavable
      protecting groups, photosensitizers, Hand gold nanoparticles for photoinduced
      RNAi. In 2005 the first report of photoinduced RNAi used a caged short
      interfering RNA (siRNA), an siRNA carrying a photocleavable protecting group.
      Caging groups block the bioactivities of target molecules, but allow for complete
      recovery of these functions via photoactivation. However, some RNAi activity can
      occur in these caged siRNAs, so it will be necessary to decrease this "leakage"
      and raise the RNAi activity restored after irradiation. This technique also uses
      UV light around 350 nm, which is cytotoxic, but in the near future we expect that
      it will be possible to use visible and near-infrared light We also examine the
      application of photochemical internalization (PCI) to RNAi technology, which
      involves a combination of photosensitizers and light. Instead of inducing RNAi
      using light, the strategy behind this method was to enhance RNAi using RNA
      carriers. Many wellknown RNA carriers deliver siRNAs into cells by endocytosis.
      The siRNAs are trapped in endocytic vesicles and have to be released into the
      cytoplasm in order to express their activity. To achieve the endosomal escape of
      siRNAs, PCI technology employed photosensitizers to generate light-dependent
      reactive oxygen species (ROS) that disrupted the endocytic vesicles. In most
      studies, RNAi-mediated knockdown of the target gene was detected even without
      PCI. Recently, a polymer capable of trapping the siRNA in endocytic vesicles
      controlled RNAi almost entirely by light. CLIP-RNAi uses photosensitizing carrier
      proteins that can be activated over a wide range of visible light wavelengths.
      With this method RNA carrier/siRNA complexes are completely trapped within
      endosomes, and RNAi is controlled strictly by light. Such precise, light
      dependent control will open up new possibilities for cellular and molecular
      biology and therapy. Most recently, gold nanoparticles (AuNPs) conjugated to
      siRNA have provided temporal and spatial control of RNAi. The light-dependent
      melting of AuNPs accompanied by a shape transformation induces the release of
      thiolated siRNAs from AuNPs. In this method, the unique optical properties of the
      AuNP enable deep penetration of the excitation light into tissues at nearinfrared
      wavelengths. The development of photoinduced RNAi technology will lead to novel
      insights into gene functions and selective drug delivery, and many other
      scientific fields will continue to influence its progress.

PMID- 22360586
TI  - Successful reduction of a high defibrillation threshold by a combined
      implantation of a subcutaneous array and azygos vein lead.
AB  - A 72-year-old man with nonischemic cardiomyopathy was referred because his
      implantable cardioverter defibrillator had failed to terminate spontaneous
      ventricular fibrillation (VF). Defibrillation threshold (DFT) testing confirmed
      that 830-V shocks failed to defibrillate VF despite optimization of the biphasic
      waveform and reversal of shock polarity. The placement of a new right ventricular
      lead and the addition of a subcutaneous array failed to defibrillate VF at 830 V.
      The combination of a subcutaneous array and azygos vein coil successfully
      defibrillated VF. The mechanism for successful DFT reduction was likely greater
      current supplied to the posterior basal left ventricle by the azygos vein lead.

PMID- 22360587
TI  - Symplocin A, a linear peptide from the Bahamian cyanobacterium Symploca sp.
      Configurational analysis of N,N-dimethylamino acids by chiral-phase HPLC of
      naphthacyl esters.
AB  - The absolute stereostructures of the components of symplocin A (3), a new N,N
      dimethyl-terminated peptide from the Bahamian cyanobacterium Symploca sp., were
      assigned from spectroscopic analysis, including MS, 2D NMR, and Marfey's
      analysis. The complete absolute configuration of symplocin A, including the
      unexpected D-configurations of the terminal N,N-dimethylisoleucine and valic acid
      residues, was assigned by chiral-phase HPLC of the corresponding 2-naphthacyl
      esters, a highly sensitive, complementary strategy for assignment of N-blocked
      peptide residues where Marfey's method is ineffectual or other methods fall
      short. Symplocin A exhibited potent activity as an inhibitor of cathepsin E
      (IC(50) 300 pM).

PMID- 22360588
TI  - Egg dispersal in the acanthocephalan Acanthocephalus dirus: field data.
AB  - Among acanthocephalans, eggs are typically dispersed in the feces of definitive
      hosts. A recent laboratory-based study provided support for the hypothesis that
      some female acanthocephalans (Acanthocephalus dirus) carry eggs into the
      environment prior to dispersal. Here, we examined the potential occurrence of
      this relationship under natural conditions. Using 6 field surveys, we searched
      the sediment of a local stream to determine whether the bodies of A. dirus
      females could be located. We recovered the bodies of 24 intact A. dirus
      individuals from the stream sediment, of which 5 were mature females. All 5 of
      the mature females contained mature eggs, with 1 female carrying approximately
      10,000. These results are consistent with the interpretation that eggs can be
      dispersed from the bodies of female A. dirus in nature. We also found that there
      was significant variation in the number of mature eggs present in the females,
      with 4 of the 5 females carrying fewer than 400 mature eggs. In addition, we
      recovered approximately 20,000 mature eggs from a fecal pellet that had been
      expelled from a fish. We propose that eggs may be dispersed both in the feces of
      definitive hosts and from the bodies of expelled female A. dirus under natural
      conditions.

PMID- 22360589
TI  - Decision-making around moving on from full-time education: the roles and
      experiences of parents of disabled young people with degenerative conditions.
AB  - Little is known about the decision-making processes that take place within
      families when a disabled young person is moving on from full-time education and,
      particularly, parents' roles and experiences. This paper reports the analysis of
      data collected from a subsample of parents (representing seventeen families)
      participating in the Choice and Change Project who had discussed choices
      associated with their child leaving full-time education. (The Choice and Change
      Project is a longitudinal, qualitative study of choice-making by four different
      groups of service users including disabled young people with degenerative
      conditions and their parents.) The data were collected from parents during up to
      three semi-structured interviews conducted over a thirty-month period.
      Descriptive theories of decision-making informed the analysis. Parents differed
      in the extent to which they were actively involved in making choices about the
      'destination' of their child after leaving full-time education. To some extent,
      the ability of the young person to make choices themselves influenced this.
      Parents who were assuming responsibility for making choices stressed the
      importance of having relevant information and felt professionals had a key role
      to play in supporting access to information. Parents used a number of criteria to
      guide their choice-making, including distance from home, perceived quality of the
      environment and staff and the young person's responses to the setting. Much of
      the information needed to make a choice required a visit to all the possible
      options. Ensuring such visits were positive and useful experiences for themselves
      and their child could be very difficult; support to achieve these visits was
      highly valued but not routinely provided. The study also highlights the lack of
      recognition given to the significant amount of work that many parents undertake
      to ensure that a choice is realised, and also to the emotional journey parents
      take when making or assisting in such decisions.

PMID- 22360590
TI  - Microvascular changes in late-life schizophrenia and mood disorders:
      stereological assessment of capillary diameters in anterior cingulate cortex.
AB  - AIMS: Previous neuroimaging reports described morphological and functional
      abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood
      disorders. In earlier neuropathological studies, microvascular changes that could
      affect brain perfusion in these disorders have rarely been studied. Here, we
      analysed morphological parameters of capillaries in this area in elderly cases
      affected by these psychiatric disorders. METHODS: We analysed microvessel
      diameters in the dorsal and subgenual parts of the ACC in eight patients with
      schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with
      sporadic major depression, and seven age- and gender-matched control cases on
      sections stained with modified Gallyas silver impregnation using a stereological
      counting approach. All individuals were drug-naive or had received psychotropic
      medication for less than 6 months, and had no history of substance abuse.
      Statistical analysis included Kruskal-Wallis group comparisons with Bonferroni
      correction as well as multivariate regression models. RESULTS: Mean capillary
      diameter was significantly decreased in the dorsal and subgenual parts of areas
      24 in bipolar and unipolar depression cases, both in layers III and V, whereas
      schizophrenia patients were comparable with controls. These differences persisted
      when controlling for age, local neuronal densities, and cortical thickness. In
      addition, cortical thickness was significantly smaller in both layers in
      schizophrenia patients. CONCLUSIONS: Our findings indicate that capillary
      diameters in bipolar and unipolar depression but not in schizophrenia are reduced
      in ACC. The significance of these findings is discussed in the light of the
      cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood
      disorders.

PMID- 22360591
TI  - Time courses of attentional modulation in neural amplification and
      synchronization measured with steady-state visual-evoked potentials.
AB  - Endogenous attention modulates the amplitude and phase coherence of steady-state
      visual-evoked potentials (SSVEPs). In efforts to decipher the neural mechanisms
      of attentional modulation, we compared the time course of attentional modulation
      of SSVEP amplitude (thought to reflect the magnitude of neural population
      activity) and phase coherence (thought to reflect neural response
      synchronization). We presented two stimuli flickering at different frequencies in
      the left and right visual hemifields and asked observers to shift their attention
      to either stimulus. Our results demonstrated that attention increased SSVEP phase
      coherence earlier than it increased SSVEP amplitude, with a positive correlation
      between the attentional modulations of SSVEP phase coherence and amplitude.
      Furthermore, the behavioral dynamics of attention shifts were more closely
      associated with changes in phase coherence than with changes in amplitude. These
      results are consistent with the possibility that attention increases neural
      response synchronization, which in turn leads to increased neural population
      activity.

PMID- 22360592
TI  - The nature of affective priming in music and speech.
AB  - The phenomenon of affective priming has caught scientific interest for over 30
      years, yet the nature of the affective priming effect remains elusive. This study
      investigated the underlying mechanism of cross-modal affective priming and the
      influence of affective incongruence in music and speech on negativities in the
      N400 time-window. In Experiment 1, participants judged the valence of affective
      targets (affective categorization). We found that music and speech targets were
      evaluated faster when preceded by affectively congruent visual word primes, and
      vice versa. This affective priming effect was accompanied by a significantly
      larger N400-like effect following incongruent targets. In this experiment, both
      spreading of activation and response competition could underlie the affective
      priming effect. In Experiment 2, participants categorized the same affective
      targets based on nonaffective characteristics. However, as prime valence was
      irrelevant to the response dimension, affective priming effects could no longer
      be attributable to response competition. In Experiment 2, affective priming
      effects were observed neither at the behavioral nor electrophysiological level.
      The results of this study indicate that both affective music and speech prosody
      can prime the processing of visual words with emotional connotations, and vice
      versa. Affective incongruence seems to be associated with N400-like effects
      during evaluative categorization. The present data further suggest a role of
      response competition during the affective categorization of music, prosody, and
      words with emotional connotations.

PMID- 22360593
TI  - Voice and emotion processing in the human neonatal brain.
AB  - Although the voice-sensitive neural system emerges very early in development, it
      has yet to be demonstrated whether the neonatal brain is sensitive to voice
      perception. We measured the EEG mismatch response (MMR) elicited by emotionally
      spoken syllables "dada" along with correspondingly synthesized nonvocal sounds,
      whose fundamental frequency contours were matched, in 98 full-term newborns aged
      1-5 days. In Experiment 1, happy syllables relative to nonvocal sounds elicited
      an MMR lateralized to the right hemisphere. In Experiment 2, fearful syllables
      elicited stronger amplitudes than happy or neutral syllables, and this response
      had no sex differences. In Experiment 3, angry versus happy syllables elicited an
      MMR, although their corresponding nonvocal sounds did not. Here, we show that
      affective discrimination is selectively driven by voice processing per se rather
      than low-level acoustical features and that the cerebral specialization for human
      voice and emotion processing emerges over the right hemisphere during the first
      days of life.

PMID- 22360594
TI  - Action-sound coincidences suppress evoked responses of the human auditory cortex
      in EEG and MEG.
AB  - The N1 auditory ERP and its magnetic counterpart (N1[m]) are suppressed when
      elicited by self-induced sounds. Because the N1(m) is a correlate of auditory
      event detection, this N1 suppression effect is generally interpreted as a
      reflection of the workings of an internal forward model: The forward model
      captures the contingency (causal relationship) between the action and the sound,
      and this is used to cancel the predictable sensory reafference when the action is
      initiated. In this study, we demonstrated in three experiments using a novel
      coincidence paradigm that actual contingency between actions and sounds is not a
      necessary condition for N1 suppression. Participants performed time interval
      production tasks: They pressed a key to set the boundaries of time intervals.
      Concurrently, but independently of keypresses, a sequence of pure tones with
      random onset-to-onset intervals was presented. Tones coinciding with keypresses
      elicited suppressed N1(m) and P2(m), suggesting that action-stimulus contiguity
      (temporal proximity) is sufficient to suppress sensory processing related to the
      detection of auditory events.

PMID- 22360595
TI  - Neuronal correlates of perception, imagery, and memory for familiar tunes.
AB  - We used fMRI to investigate the neuronal correlates of encoding and recognizing
      heard and imagined melodies. Ten participants were shown lyrics of familiar
      verbal tunes; they either heard the tune along with the lyrics, or they had to
      imagine it. In a subsequent surprise recognition test, they had to identify the
      titles of tunes that they had heard or imagined earlier. The functional data
      showed substantial overlap during melody perception and imagery, including
      secondary auditory areas. During imagery compared with perception, an extended
      network including pFC, SMA, intraparietal sulcus, and cerebellum showed increased
      activity, in line with the increased processing demands of imagery. Functional
      connectivity of anterior right temporal cortex with frontal areas was increased
      during imagery compared with perception, indicating that these areas form an
      imagery-related network. Activity in right superior temporal gyrus and pFC was
      correlated with the subjective rating of imagery vividness. Similar to the
      encoding phase, the recognition task recruited overlapping areas, including
      inferior frontal cortex associated with memory retrieval, as well as left middle
      temporal gyrus. The results present new evidence for the cortical network
      underlying goal-directed auditory imagery, with a prominent role of the right pFC
      both for the subjective impression of imagery vividness and for on-line mental
      monitoring of imagery-related activity in auditory areas.

PMID- 22360596
TI  - Public understanding of drug therapy.
AB  - Knowing some basic principles about medicines would help patients to understand
      drug therapy and to help and encourage them to use it well. These principles
      relate to the categories and names of drugs, their different uses, how they reach
      the site of action (absorption, distribution, fate), how they produce their
      effects, both beneficial and harmful, the time courses of drug actions, how the
      pattern and intensity of the effects of a drug depend on dose and timing, drug
      interactions, how drug effects are demonstrated and investigated and sources of
      information and their trustworthiness. These basic principles are an essential
      part of health literacy and understanding them would enable individuals to
      comprehend better the information that they are likely to receive about medicines
      that they will take. Different populations need different types of education. For
      schoolchildren, the principles could fit into biology and domestic science
      teaching, starting in the later years of primary school or early in secondary
      school. A teaching package would also be needed for their teachers. For adults,
      web-based learning seems the most practical option. Web-based programmes could be
      supported by the NHS and professional bodies and through public libraries and
      local community health services. Specific groups for targeting could include
      young mothers and carers of chronically ill people. For retired people, one could
      envisage special programmes, perhaps in collaboration with the University of the
      Third Age. Conversations between patients and professionals would then become
      more effective and help shared decision making.

PMID- 22360597
TI  - Pseudomonas putida growing at low temperature shows increased levels of CrcZ and
      CrcY sRNAs, leading to reduced Crc-dependent catabolite repression.
AB  - The Crc protein of Pseudomonas inhibits the expression of genes involved in the
      transport and assimilation of a number of non-preferred carbon sources when
      preferred substrates are available, thus coordinating carbon metabolism. Crc acts
      by binding to target mRNAs, inhibiting their translation. In Pseudomonas putida,
      the amount of free Crc available is controlled by two sRNAs, CrcY and CrcZ, which
      bind to and sequester Crc. The levels of these sRNAs vary according to metabolic
      conditions. Pseudomonas putida grows optimally at 30 degrees C, but can also
      thrive at 10 degrees C. The present work shows that when cells grow exponentially
      at 10 degrees C, the repressive effect of Crc on many genes is significantly
      reduced compared with that seen at 30 degrees C. Total Crc levels were similar at
      both temperatures, but those of CrcZ and CrcY were significantly higher at 10
      degrees C. Therefore, Crc-mediated repression may, at least in part, be reduced
      at 10 degrees C because the fraction of Crc protein sequestered by CrcZ and CrcY
      is larger, reducing the amount of free Crc available to bind its targets. This
      may help P. putida to face cold stress. The results reported might help
      understanding the behaviour of this bacterium in bioremediation or
      rhizoremediation strategies at low temperatures.

PMID- 22360598
TI  - The signaling mechanism of ambient pH sensing and adaptation in yeast and fungi.
AB  - The four protein complexes termed endosomal sorting complexes required for
      transport (ESCRT) are key mediators of multivesicular body sorting/formation,
      retroviral budding and cell abscission, which share a membrane deformation
      process with the same topological change: vesicles budding away from the
      cytoplasm. Independent studies of the signal transduction pathways that mediate
      ambient pH sensing and adaptation in yeast and fungi revealed that these pathways
      share a conserved signaling mechanism that utilizes ESCRT complexes for its
      activation. This pathway in Saccharomyces cerevisiae, termed the Rim101 pathway,
      consists of both a sensing complex, which senses ambient alkaline pH, and a
      proteolytic complex, which proteolyzes and thereby activates the key
      transcription factor Rim101. Since the proteolytic complex is thought to be
      formed and activated on a platform of a multimerized ESCRT-III component Snf7,
      the organization, regulation and function of this pathway are dependent on the
      function of ESCRT complexes.

PMID- 22360601
TI  - ERES (ER exit sites) and the "secretory unit concept".
AB  - The higher plant Golgi apparatus consists of hundreds of individual Golgi stacks
      which move along the cortical ER, propelled by the actomysin system. Anterograde
      and retrograde transport between the endoplasmic reticulum (ER) and the plant
      Golgi occurs over a narrow interface (around 500 nm) and is generally considered
      to be mediated by COP-coated vesicles. Previously, ER exit sites (ERES) have been
      identified on the basis of to localization of transiently expressed COPII-coat
      proteins. As a consequence it has been held that ERES in higher plants are
      intimately associated with Golgi stacks, and that both move together as an
      integrated structure: the "secretory unit". Using a new COPII marker, as well as
      YFP-SEC24 (a bona fide COPII coat protein), we have made observations on tobacco
      leaf epidermis at high resolution in the CLSM. Our data clearly shows that COPII
      fluorescence is associated with the Golgi stacks rather than the surface of the
      ER and probably represents the temporary accumulation of COPII vesicles in the
      Golgi matrix prior to fusion with the cis-Golgi cisternae. We have calculated the
      numbers of COPII vesicles which would be required to provide a typical Golgi
      associated COPII-fluorescent signal as being much less than 20. We have discussed
      the consequences of this and question the continued usage of the term "secretory
      unit".

PMID- 22360600
TI  - Structural, EPR, and Mossbauer characterization of (MU-alkoxo)(MU
      carboxylato)diiron(II,III) model complexes for the active sites of mixed-valent
      diiron enzymes.
AB  - To obtain structural and spectroscopic models for the diiron(II,III) centers in
      the active sites of diiron enzymes, the (MU-alkoxo)(MU-carboxylato)diiron(II,III)
      complexes [Fe(II)Fe(III)(N-Et-HPTB)(O(2)CPh)(NCCH(3))(2)](ClO(4))(3) (1) and
      [Fe(II)Fe(III)(N-Et-HPTB)(O(2)CPh)(Cl)(HOCH(3))](ClO(4))(2) (2) (N-Et-HPTB =
      N,N,N',N'-tetrakis(2-(1-ethyl-benzimidazolylmethyl))-2-hydroxy-1,3
      diaminopropane) have been prepared and characterized by X-ray crystallography, UV
      visible absorption, EPR, and Mossbauer spectroscopies. Fe1-Fe2 separations are
      3.60 and 3.63 A, and Fe1-O1-Fe2 bond angles are 128.0 degrees  and 129.4 degrees 
      for 1 and 2, respectively. Mossbauer and EPR studies of 1 show that the Fe(III)
      (S(A) = 5/2) and Fe(II) (S(B) = 2) sites are antiferromagnetically coupled to
      yield a ground state with S = 1/2 (g= 1.75, 1.88, 1.96); Mossbauer analysis of
      solid 1 yields J = 22.5 +/- 2 cm(-1) for the exchange coupling constant (H =
      JS(A).S(B) convention). In addition to the S = 1/2 ground-state spectrum of 1,
      the EPR signal for the S = 3/2 excited state of the spin ladder can also be
      observed, the first time such a signal has been detected for an
      antiferromagnetically coupled diiron(II,III) complex. The anisotropy of the
      (57)Fe magnetic hyperfine interactions at the Fe(III) site is larger than
      normally observed in mononuclear complexes and arises from admixing S > 1/2
      excited states into the S = 1/2 ground state by zero-field splittings at the two
      Fe sites. Analysis of the "D/J" mixing has allowed us to extract the zero-field
      splitting parameters, local g values, and magnetic hyperfine structural
      parameters for the individual Fe sites. The methodology developed and followed in
      this analysis is presented in detail. The spin Hamiltonian parameters of 1 are
      related to the molecular structure with the help of DFT calculations. Contrary to
      what was assumed in previous studies, our analysis demonstrates that the
      deviations of the g values from the free electron value (g = 2) for the
      antiferromagnetically coupled diiron(II,III) core in complex 1 are predominantly
      determined by the anisotropy of the effective g values of the ferrous ion and
      only to a lesser extent by the admixture of excited states into ground-state ZFS
      terms (D/J mixing). The results for 1 are discussed in the context of the data
      available for diiron(II,III) clusters in proteins and synthetic diiron(II,III)
      complexes.

PMID- 22360603
TI  - Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related
      portal hypertension after liver transplantation.
AB  - This is a single center retrospective review of 19 consecutive liver transplant
      (LT) patients with hepatitis C virus (HCV)-related graft recurrent hepatitis who
      underwent transjugular intrahepatic portosystemic shunt (TIPS) at a median
      interval of 21 months (range: 5-50) from LT. Indications were refractory ascites
      in 11 patients (57.9%), hydrothorax in six (31.6%), and both in two (10.5%). TIPS
      was successful in 94.7% of cases (18/19) with only one procedure-related
      mortality (5.3%) owing to sepsis on day 35. At a median follow-up of 23 months
      (range: one month-nine yr), TIPS allowed for symptoms resolution in 16 patients
      (84.2%), with ascites resolving in all cases and hydrothorax persisting in 2.
      Post-TIPS patient survival at six months, one yr, and three yr was 84.2%, 73.7%,
      and 56.8%, respectively. We compared these results with a control group of 29
      patients with HCV recurrence but without unresponsive ascites or hydrothorax.
      Patients in the control group had better survival than patients undergoing TIPS
      placement. However, survival of TIPS patients with a MELD score lower than or
      equal to 12 was similar to that of the control group. We conclude that TIPS may
      be used to treat complications secondary to HCV.

PMID- 22360602
TI  - Final results of the phase II study of rabbit anti-thymocyte globulin,
      ciclosporin, methylprednisone, and granulocyte colony-stimulating factor in
      patients with aplastic anaemia and myelodysplastic syndrome.
AB  - This report describes the final results of a Phase II clinical trial
      investigating the efficacy of rabbit antithymocyte globulin (rATG), ciclosporin,
      steroids, and granulocyte colony-stimulating factor (GCSF) in patients with
      untreated aplastic anaemia (AA), or low to intermediate-risk and hypocellular
      myelodysplastic syndrome (MDS). We treated 24 patients each with AA and MDS with
      rATG (3.5 mg/kg/d * 5; reduced to 2.5 mg/kg/d * 5 in patients with MDS >= 55
      years), ciclosporin (5 mg/kg orally daily * 6 months), steroids (1 mg/kg daily,
      tapered off over 1 month), and GCSF. The overall response rate in AA patients was
      64% compared to 25% in MDS patients. The median time to response was 3 months in
      AA patients and 4 months in MDS patients. Pretreatment clinical characteristics,
      such as age, sex, blood counts, cellularity, cytogenetics, or HLA-DR15 status,
      did not predict for response. Response to therapy, however, predicted for
      improved overall survival (OS), with a 3-year OS of 89% vs. 43% in responders
      versus non-responders, respectively (P < 0.001). Infusion reactions occurred in
      about half the patients and were manageable. Myelosuppression, elevation in liver
      enzymes, and infections were common. The early mortality in MDS patients was 13%
      vs. 0% in AA patients.

PMID- 22360604
TI  - Enantioselective total synthesis of (S)-bisoranjidiol, an axially chiral
      bisanthraquinone.
AB  - The first enantioselective total synthesis of the bisanthraquinone (S)
      bisoranjidiol and an unnatural regioisomer has been accomplished. Key features of
      the synthesis include the asymmetric oxidative biaryl coupling of a hindered 8
      substituted 2-naphthol, selective para-quinone formation, and regioselective
      tandem Diels-Alder/aromatization reactions.

PMID- 22360605
TI  - Civil society perspectives on negative biomedical HIV prevention trial results
      and implications for future trials.
AB  - Community engagement is crucial to ongoing development and testing of sorely
      needed new biomedical HIV prevention technologies. Yet, negative trial results
      raise significant challenges for community engagement in HIV prevention trials,
      including the early termination of the Cellulose Sulfate microbicide trial and
      two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to
      explore the perspectives and experiences of civil society organization (CSO)
      representatives regarding negative HIV prevention trial results and perceived
      implications for future trials. We conducted in-depth interviews with 14
      respondents from a broad range of South African and international CSOs, and
      analyzed data using thematic analysis. CSO representatives reported
      disappointment in response to negative trial results, but acknowledged such
      outcomes as inherent to clinical research. Respondents indicated that in theory
      negative trial results seem likely to impact on willingness to participate in
      future trials, but that in practice people in South Africa have continued to
      volunteer. Negative trial results were described as having contributed to
      improving ethical standards, and to a re-evaluation of the scientific agenda.
      Such negative results were identified as potentially impacting on funding for
      trials and engagement activities. Our findings indicate that trial closures may
      be used constructively to support opportunities for reflection and renewed
      vigilance in strategies for stakeholder engagement, communicating trial outcomes,
      and building research literacy among communities; however, these strategies
      require sustained resources for community engagement and capacity-building.

PMID- 22360606
TI  - Antidiabetic effects of natural plant extracts via inhibition of carbohydrate
      hydrolysis enzymes with emphasis on pancreatic alpha amylase.
AB  - INTRODUCTION: The increasing prevalence of type 2 diabetes mellitus and the
      negative clinical outcomes observed with the commercially available anti-diabetic
      drugs have led to the investigation of new therapeutic approaches focused on
      controlling postprandrial glucose levels. The use of carbohydrate digestive
      enzyme inhibitors from natural resources could be a possible strategy to block
      dietary carbohydrate absorption with less adverse effects than synthetic drugs.
      AREAS COVERED: This review covers the latest evidence regarding in vitro and in
      vivo studies in relation to pancreatic alpha-amylase inhibitors of plant origin,
      and presents bioactive compounds of phenolic nature that exhibit anti-amylase
      activity. EXPERT OPINION: Pancreatic alpha-amylase inhibitors from traditional
      plant extracts are a promising tool for diabetes treatment. Many studies have
      confirmed the alpha-amylase inhibitory activity of plants and their bioactive
      compounds in vitro, but few studies corroborate these findings in rodents and
      very few in humans. Thus, despite some encouraging results, more research is
      required for developing a valuable anti-diabetic therapy using pancreatic alpha
      amylase inhibitors of plant origin.

PMID- 22360607
TI  - Site specific interaction of the polyphenol EGCG with the SEVI amyloid precursor
      peptide PAP(248-286).
AB  - Recently, a 39 amino acid peptide fragment from prostatic acid phosphatase has
      been isolated from seminal fluid that can enhance infectivity of the HIV virus by
      up to 4-5 orders of magnitude. PAP(248-286) is effective in enhancing HIV
      infectivity only when it is aggregated into amyloid fibers termed SEVI. The
      polyphenol EGCG (epigallocatechin-3-gallate) has been shown to disrupt both SEVI
      formation and HIV promotion by SEVI, but the mechanism by which it accomplishes
      this task is unknown. Here, we show that EGCG interacts specifically with the
      side chains of monomeric PAP(248-286) in two regions (K251-R257 and N269-I277) of
      primarily charged residues, particularly lysine. The specificity of interaction
      to these two sites is contrary to previous studies on the interaction of EGCG
      with other amyloidogenic proteins, which showed the nonspecific interaction of
      EGCG with exposed backbone sites of unfolded amyloidogenic proteins. This
      interaction is specific to EGCG as the related gallocatechin (GC) molecule, which
      shows greatly decreased antiamyloid activity, exhibits minimal interaction with
      monomeric PAP(248-286). The EGCG binding was shown to occur in two steps, with
      the initial formation of a weakly bound complex followed by a pH dependent
      formation of a tightly bound complex. Experiments in which the lysine residues of
      PAP(248-286) have been chemically modified suggest the tightly bound complex is
      created by Schiff-base formation with lysine residues. The results of this study
      could aid in the development of small molecule inhibitors of SEVI and other
      amyloid proteins.

PMID- 22360608
TI  - Molecular and morphological evidence for the Holarctic distribution of Urogonimus
      macrostomus (Rudolphi, 1803) Monticelli, 1888 (Digenea: Leucochloridiidae).
AB  - Species of Urogonimus Monticelli, 1888 (Leucochloridiidae Poche, 1907) are
      difficult to distinguish using adult morphology, and their taxonomy has been
      repeatedly subjected to revision. Some Nearctic species have been regarded as
      synonymous with the Palearctic type species Urogonimus macrostomus (Rudolphi,
      1803) Monticelli, 1888. This implies that U. macrostomus is present in the
      Nearctic, but there is no additional evidence for this putative distribution. We
      collected trematodes morphologically indistinguishable from U. macrostomus from a
      house sparrow (Passer domesticus) in Edmonton, Alberta, Canada. Sequences 2958 bp
      in total length from the small and large subunits of ribosomal DNA from 2
      specimens were 99.8-100% identical to those of U. macrostomus in the Ukraine and
      Japan. In light of the lack of morphological differences and small degree of
      genetic variation, we consider the specimens we collected to be conspecific with
      U. macrostomus in the Palearctic, and the Holarctic range of the species is thus
      supported. Sequences from a more rapidly evolving gene, cytochrome c oxidase 1,
      were obtained to aid future study of this and related species.

PMID- 22360609
TI  - Applications of nano-baskets in drug development: high solubility and low
      toxicity.
AB  - The importance of calixarene nanobaskets in drug development and controlling
      their toxicity comes back to their ability to encapsulate the drug species and
      biological compounds. New complexes show improved physical characteristics, such
      as more solubility in water and enhanced chemical properties, including less
      toxicity in biological systems. Moreover, the covalent bonding, inclusion
      encapsulation, and induction activities of calixarenes lead to improving the
      activity of drug molecules. This review article deals with the importance of
      calixarene-based drugs and illustrates their potentials in drug development and
      toxicity control. The main aim and novelty of this study was to introduce the
      role and the action of calixarene scaffolds and their conjugated upper and lower
      rims as well as their binding mechanism in biomedical systems. The main aspects
      of this approach are classified in four categories and are discussed according to
      the results of recent researches.

PMID- 22360610
TI  - Mechanisms mediating propofol protection of pulmonary epithelial cells against
      lipopolysaccharide-induced cell death.
AB  - Propofol (2,6-diisopropylphenol) is an anaesthetic agent with anti-oxidant
      properties. The aim of the present study was to determine whether propofol can
      protect pulmonary epithelial (A549) cells against lipopolysaccharide (LPS)
      induced cell death and, if so, the mechanisms involved. The effects of LPS alone
      and in combination with propofol on A549 cell death were investigated. Cell
      viability was determined using the colourimetric 3-(4,5-dimethyl-2 thiazoyl)-2,5
      diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic A549 cells were detected
      by flow cytometry, as propidium iodide-negative and annexin-V-positive cells, and
      terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end
      labelling (TUNEL). Mitochondrial membrane potential (MMP), caspase 9 activity,
      Ca(2+)  concentrations and reactive oxygen species (ROS) were analysed by
      immunofluorescent methods. Aconitase 2 (ACO2), microtubule-associated light chain
      3 (LC3) and beclin-1 levels were evaluated using reverse transcription-polymerase
      chain reaction and/or western blot analysis. Exposure of A549 cells to 1-50
      MUg/mL LPS for 3-24 h resulted in the concentration- and time-dependent induction
      of cell death. Cell apoptosis accounted for approximately 77% of cell death
      induced by LPS. Propofol (5-150 MUmol/L) concentration-dependently inhibited LPS
      induced A549 cell death. This protective effect of propofol was accompanied by
      prevention of LPS-induced mitochondrial dysfunction (reductions in MMP, ACO2
      expression and ATP) and was associated with the inhibition of LPS-induced
      activation of apoptotic signals (caspase 9 activity, ROS overproduction and
      Ca(2+)  accumulation). In addition, propofol blocked LPS-induced overexpression
      of the autophagy-associated proteins LC3 and beclin-1. The data indicate that
      propofol protects A549 cells against LPS-induced apoptosis, and probably
      autophagy, by blocking LPS-induced activation of ROS/caspase 9 pathways and
      upregulation of LC3 and beclin-1, respectively.

PMID- 22360611
TI  - Ablation of atrial fibrillation using an irrigated-tip catheter: open or closed?

PMID- 22360612
TI  - Split catheters in children on chronic hemodialysis: a single-center experience.
AB  - Tunneled central venous catheters (CVCs) play an increasing role as vascular
      access for chronic hemodialysis (HD) in children, but limited data exist about
      the optimal CVC choice. We analyzed the outcome, efficacy, and complications of
      tunneled CVCs, placed in our unit in the last 3 years. Nineteen 10 F Split-Cath
      CVCs (two separate catheters fused along their length) were placed in 10
      children, median age 9.19 years (range 2.15-13.31) and body weight (BW) between
      10 and 40 kg. CVCs survival at 1, 3, 6, and 12 months was 94%, 77%, 51%, and 34%,
      respectively. Catheter survival was higher in children with BW > 20 kg than in
      smaller patients. Median survival was higher than that of 11 Quinton Permcath
      CVCs, placed in five children in the preceding 2 years (280 vs. 45 days, P <
      0.05). Median blood flow rate and indices of HD adequacy were higher in children
      with lower BW (<20 kg vs. 20-30 kg vs. >30 kg) than in those with higher BW.
      Incidence of exit site and bloodstream infections was 2.32 and 0.66/1000 CVC
      days, respectively. One case of hemothorax due to subclavian artery puncture
      occurred during CVC placement. In conclusion, Split-Cath 10 F CVC allows for
      effective dialysis in children undergoing HD, particularly those between 10 and
      30 kg BW. Catheter survival is acceptable, but could be improved in small
      children.

PMID- 22360613
TI  - Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing
      breast cancer cells, from thermophilic Aspergillus terreus.
AB  - Breast cancer cells express ABCG2 transporters, which mediate multidrug
      resistance. Discovering a novel compound that can suppress ABCG2 expression and
      restore drug sensitivity could be the key to improving breast cancer
      therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as
      well as 12 other known compounds, was isolated from Aspergillus terreus. The
      structure of the new isolate was determined by spectroscopic methods. Among these
      isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7
      cells. Treatment with terrein (2) significantly suppressed growth of ABCG2
      expressing breast cancer cells. This suppressive effect was achieved by inducing
      apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling
      pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the
      side-population phenotype.

PMID- 22360614
TI  - Quantitative structure-activity relationship studies on Na+,K(+)-ATPase
      inhibitors.

PMID- 22360615
TI  - Home care in England: markets in the context of under-funding.
AB  - This paper traces developments in English home care services over two decades
      from the early 1990s. This longer-term perspective is used to show how factors
      shaping the broader restructuring of the English welfare state have impacted on
      home care services in particular. The two most salient features of these policies
      have been public sector funding constraints and extensive marketisation. Despite
      demographic trends, home care services have been deeply affected by the
      structural underfunding of long-term care services in general. The sector has
      been further shaped by the creation first of a 'mixed economy' of supply, with
      local authorities purchasing services from external providers instead of their
      own in-house services; and by the more recent introduction of a 'mixed economy'
      of purchasing, as greater emphasis is placed on individual choice and
      personalisation. The outcomes of these dual pressures are an increasingly
      residual publicly funded home care service and a growing role for private funding
      and supply. These outcomes have potentially damaging consequences for the quality
      of both public and private home care.

PMID- 22360617
TI  - The role of chromatin in Plasmodium gene expression.
AB  - The malaria parasite Plasmodium falciparum dynamically regulates transcription of
      the majority of its genes during its intraerythrocytic developmental cycle.
      Chromatin is an important contributor to this tight regulation of gene
      expression. P. falciparum appears to utilize most of the mechanisms of chromatin
      creation and modification found in other eukaryotes, although it occasionally
      uses them in surprising ways. Much of the P. falciparum genome is maintained in a
      euchromatic state, potentially permissive for transcription and heterochromatin
      appears to have a specialized role limited to silencing islands of genes involved
      in redundant host-parasite interactions. P. falciparum histones share canonical
      modifications with other eukaryotes but also have unique modifications of unknown
      function including hyperacetylations of two alternative histones possibly
      involved in gene regulation. Much of our knowledge of chromatin regulation of
      gene expression in P. falciparum derives from the study of virulence genes that
      are subject to chromatin regulatory mechanisms ranging from histone modifications
      and nucleosomal occupancy to non-protein-coding RNAs and subnuclear architecture.
      These mechanisms will be discussed along with other characterized components of
      P. falciparum chromatin.

PMID- 22360618
TI  - Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of
      the head and neck.
AB  - Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population and
      have the potential to suppress immune responses via diverse mechanisms. In recent
      studies, a new subset of MDSC was identified by the markers CD14(+) and HLA-DR(-)
      in the peripheral blood from cancer patients. In this study, we investigated the
      proportions and characteristics of CD14(+) HLA-DR(-) cells in patients with
      squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage
      of CD14(+) HLA-DR(-) cells was significantly elevated in patients relative to
      healthy donors and the sorted CD14(+) HLA-DR(-) cells were able to suppress
      effectively both the proliferation and IFN-gamma production of anti-CD3/anti-CD28
      stimulated T cells, suggesting that CD14(+) HLA-DR(-) cells in patients with
      SCCHN contribute to the immune suppressive status. Furthermore, CD14(+) HLA-DR(-)
      cells revealed a higher level of CD86 and PD-L1 expression and transforming
      growth factor (TGF)-beta production than CD14(+) HLA-DR(+) cells. Addition of
      anti-CD86 mAb, anti-PD-L1 mAb and anti-TGF-beta mAb partially restored T-cell
      proliferation and IFN-gamma production, respectively, indicating that the
      suppressive effects of CD14(+) HLA-DR(-) cells appear to be mediated by various
      molecules, including coinhibitory molecules and cytokines. Our data suggest that
      CD14(+) HLA-DR(-) cells act as potent immunosuppressive cells and particularly
      contribute to tumor escape from the host immune system in patients with SCCHN.

PMID- 22360619
TI  - Synthesis, structural, and magnetic characterization of linear and bent geometry
      cobalt(II) and nickel(II) amido complexes: evidence of very large spin-orbit
      coupling effects in rigorously linear coordinated Co2+.
AB  - The complexes M(II){N(H)Ar(Pr(i)(6))}(2) (M = Co, 1 or Ni, 2; Ar(Pr(i)(6)) =
      C(6)H(3)-2,6(C(6)H(2)-2,4,6-Pr(i)(3))(2)), which have rigorously linear, N-M-N =
      180 degrees , metal coordination, and M(II){N(H)Ar(Me(6))}(2) (M = Co, 3 or Ni,
      4; Ar(Me(6)) = C(6)H(3)-2,6(C(6)H(2)-2,4,6-Me(3))(2)), which have bent, N-Co-N =
      144.1(4) degrees , and N-Ni-N = 154.60(14) degrees , metal coordination, were
      synthesized and characterized to study the effects of the metal coordination
      geometries on their magnetic properties. The magnetometry studies show that the
      linear cobalt(II) species 1 has a very high ambient temperature moment of about
      6.2 MU(B) (cf. spin only value = 3.87 MU(B)) whereas the bent cobalt species 3
      had a lower MU(B) value of about 4.7 MU(B). In contrast, both the linear and the
      bent nickel complexes 2 and 4 have magnetic moments near 3.0 MU(B) at ambient
      temperatures, which is close to the spin only value of 2.83 MU(B). The studies
      suggest that in the linear cobalt species 1 there is a very strong enhanced spin
      orbital coupling which leads to magnetic moments that broach the free ion value
      of 6.63 MU(B) probably as a result of the relatively weak ligand field and its
      rigorously linear coordination. For the linear nickel species 2, however, the
      expected strong first order orbital angular momentum contribution does not occur
      (cf. free ion value 5.6 MU(B)) possibly because of pi bonding effects involving
      the nitrogen p orbitals and the d(xz) and d(yz) orbitals (whose degeneracy is
      lifted in the C(2h) local symmetry of the Ni{N(H)C(ipso)}(2) array) which quench
      the orbital angular momentum.

PMID- 22360620
TI  - UK medicines policy: the role of clinical pharmacologists.
AB  - Clinical pharmacologists are the only medical specialists whose training focuses
      specifically on the safe, effective and cost-effective use of medicines,
      underpinned by an understanding of drug discovery, drug regulation, pharmacology,
      translational medicine and the performance of clinical trials. This unique
      perspective has allowed them to provide expertise and leadership in medicines
      regulation, medicines policy, health technology assessment and drug pricing.
      Clinical pharmacologists assisted in the creation of the Committee on Safety of
      Medicines (now the Commission on Human Medicines), the Yellow Card Scheme, the
      National Institute of Health and Clinical Excellence (NICE) and related
      organizations in Scotland and Wales, and contributed to clinical guidelines
      (through the Scottish Intercollegiate Guidelines Network) and the British
      National Formulary. Their research work has contributed substantially, through
      translational medicine and therapeutics, to the development of new medicines and,
      as a result, creation of health and wealth in the UK. Their work in medicines
      policy has served to protect patients from harms associated with the use of
      medicines. A reduction in the number of able junior doctors attracted to a career
      in clinical pharmacology, a reduction in the number of training posts, and an
      ageing population of academic trainers, puts the future of the specialty, and its
      contribution to patient safety and UK wealth creation, at substantial risk.
      Urgent measures are needed to convince the NHS and government that these
      essential skills should be protected and nurtured.

PMID- 22360621
TI  - The brain in vivo expresses the 2',3'-cAMP-adenosine pathway.
AB  - Although multiple biochemical pathways produce adenosine, studies suggest that
      the 2',3'-cAMP-adenosine pathway (2',3'-cAMP->2'-AMP/3'-AMP->adenosine)
      contributes to adenosine production in some cells/tissues/organs. To determine
      whether the 2',3'-cAMP-adenosine pathway exists in vivo in the brain, we
      delivered to the brain (gray matter and white matter separately) via the inflow
      perfusate of a microdialysis probe either 2',3'-cAMP, 3',5'-cAMP, 2'-AMP, 3'-AMP,
      or 5'-AMP and measured the recovered metabolites in the microdialysis outflow
      perfusate with mass spectrometry. In both gray and white matter, 2',3'-cAMP
      increased 2'-AMP, 3'-AMP and adenosine, and 3',5'-cAMP increased 5'-AMP and
      adenosine. In both brain regions, 2'-AMP, 3-AMP and 5'-AMP were converted to
      adenosine. Microdialysis experiments in 2',3'-cyclic nucleotide-3'
      phosphodiesterase (CNPase) wild-type mice demonstrated that traumatic brain
      injury (controlled cortical impact model) activated the brain 2',3'-cAMP
      adenosine pathway; similar experiments in CNPase knockout mice indicated that
      CNPase was involved in the metabolism of endogenous 2',3'-cAMP to 2'-AMP and to
      adenosine. In CSF from traumatic brain injury patients, 2',3'-cAMP was
      significantly increased in the initial 12 h after injury and strongly correlated
      with CSF levels of 2'-AMP, 3'-AMP, adenosine and inosine. We conclude that in
      vivo, 2',3'-cAMP is converted to 2'-AMP/3'-AMP, and these AMPs are metabolized to
      adenosine. This pathway exists endogenously in both mice and humans.

PMID- 22360622
TI  - Enhanced shape-selective recognition of anion guests through complexation-induced
      organization of porphyrin hosts.
AB  - We present a fortuitous discovery of enhanced shape-selective recognition of
      anion guests that stems from a complexation-induced conformational change in
      porphyrin hosts upon anion binding. Porphyrin hosts reported here exist in a
      conformation that is not favorable to guest binding. Anions that bind strongly
      are those that can induce a conformational change in the host to allow guest
      binding. Furthermore, guests that mimic the shape of the newly formed pocket bind
      the strongest.

PMID- 22360624
TI  - The superior temporal sulcus differentiates communicative and noncommunicative
      auditory signals.
AB  - Processing the vocalizations of conspecifics is critical for adaptive social
      interaction. A species-specific voice-selective region has been identified in the
      right STS that responds more strongly to human vocal sounds compared with a
      variety of nonvocal sounds. However, the STS also activates in response to a wide
      range of signals used in communication, such as eye gaze, biological motion, and
      speech. These findings raise the possibility that the voice-selective region of
      the STS may be especially sensitive to vocal sounds that are communicative,
      rather than to all human vocal sounds. Using fMRI, we demonstrate that the voice
      selective region of the STS responds more strongly to communicative vocal sounds
      (such as speech and laughter) compared with noncommunicative vocal sounds (such
      as coughing and sneezing). The implications of these results for understanding
      the role of the STS in voice processing and in disorders of social communication,
      such as autism spectrum disorder, are discussed.

PMID- 22360623
TI  - Strategic allocation of attention reduces temporally predictable stimulus
      conflict.
AB  - Humans are able to continuously monitor environmental situations and adjust their
      behavioral strategies to optimize performance. Here we investigate the behavioral
      and brain adjustments that occur when conflicting stimulus elements are, or are
      not, temporally predictable. ERPs were collected while manual response variants
      of the Stroop task were performed in which the SOAs between the relevant color
      and irrelevant word stimulus components were either randomly intermixed or held
      constant within each experimental run. Results indicated that the size of both
      the neural and behavioral effects of stimulus incongruency varied with the
      temporal arrangement of the stimulus components, such that the random-SOA
      arrangements produced the greatest incongruency effects at the earliest
      irrelevant first SOA (-200 msec) and the constant-SOA arrangements produced the
      greatest effects with simultaneous presentation. These differences in conflict
      processing were accompanied by rapid (~150 msec) modulations of the sensory ERPs
      to the irrelevant distractor components when they occurred consistently first.
      These effects suggest that individuals are able to strategically allocate
      attention in time to mitigate the influence of a temporally predictable
      distractor. As these adjustments are instantiated by the participants without
      instruction, they reveal a form of rapid strategic learning for dealing with
      temporally predictable stimulus incongruency.

PMID- 22360625
TI  - Large-scale cortical network properties predict future sound-to-word learning
      success.
AB  - The human brain possesses a remarkable capacity to interpret and recall novel
      sounds as spoken language. These linguistic abilities arise from complex
      processing spanning a widely distributed cortical network and are characterized
      by marked individual variation. Recently, graph theoretical analysis has
      facilitated the exploration of how such aspects of large-scale brain functional
      organization may underlie cognitive performance. Brain functional networks are
      known to possess small-world topologies characterized by efficient global and
      local information transfer, but whether these properties relate to language
      learning abilities remains unknown. Here we applied graph theory to construct
      large-scale cortical functional networks from cerebral hemodynamic (fMRI)
      responses acquired during an auditory pitch discrimination task and found that
      such network properties were associated with participants' future success in
      learning words of an artificial spoken language. Successful learners possessed
      networks with reduced local efficiency but increased global efficiency relative
      to less successful learners and had a more cost-efficient network organization.
      Regionally, successful and less successful learners exhibited differences in
      these network properties spanning bilateral prefrontal, parietal, and right
      temporal cortex, overlapping a core network of auditory language areas. These
      results suggest that efficient cortical network organization is associated with
      sound-to-word learning abilities among healthy, younger adults.

PMID- 22360626
TI  - The relationship between self-efficacy and positive aspects of caregiving in
      Alzheimer's disease caregivers.
AB  - OBJECTIVES: Positive aspects of the caregiving experience may buffer caregivers
      from the many negative psychological and physical consequences of caregiving.
      Understanding what factors relate to the recognition of positive aspects of
      caregiving is important for the enhancement of caregiver well-being. Self
      efficacy is a potentially modifiable psychological construct that has been
      associated with positive thinking, improved control of negative affect, and
      enhanced motivation. METHODS: This study examined the relationship between
      positive aspects of caregiving and self-efficacy among 57 family members caring
      for a loved one with Alzheimer's disease. Participant data was gathered through
      individual interviews conducted as a part of a larger randomized controlled trial
      of a caregiver intervention. RESULTS: We found that self-efficacy accounted for a
      significant percentage of the variance in positive aspects of caregiving after
      controlling for other factors commonly associated with positive aspects of
      caregiving including caregiver demographics, care recipient neuropsychiatric
      symptoms, and caregiver depression. CONCLUSIONS: Our results suggest that high
      self-efficacy relates to caregivers' perception of positive aspects of the
      caregiving experience.

PMID- 22360628
TI  - Integrating pharmacology and clinical pharmacology in universities.
AB  - Continuing development of safe and effective new medicines is critically
      important for global health, social prosperity and the economy. The drug
      discovery-development pipeline depends critically on close partnerships between
      scientists and clinicians and on educational programmes that ensure that the
      pharmacological workforce, in its broadest sense, is fit for purpose. Here I
      consider factors that have influenced the development of basic and clinical
      pharmacology in UK universities over the past 40 years and discuss ways in which
      basic pharmacologists, clinical pharmacologists and scientists from different
      disciplines can work together effectively, while retaining their professional
      identities and fostering developments in their disciplines. Specifically, I
      propose the establishment of Institutes of Drug Discovery and Development, whose
      activities could include development and implementation of a translational
      pharmacology research strategy, drawing on the collective expertise of the
      membership and the university as whole; provision of a forum for regular seminars
      and symposia to promote the discipline, encourage collaboration and develop a
      cohesive community; provision of a research advisory service, covering, for
      example, data management, applications for ethics permission, clinical trials
      design, statistics and regulatory affairs; liaison with potential funders and
      leadership of major funding bids, including funding for doctoral training;
      provision of advice on intellectual property protection and the commercialization
      of research; liaison with corporate partners to facilitate collaboration,
      knowledge transfer and effective translation; and leadership of undergraduate and
      postgraduate education in basic and clinical pharmacology and related sciences
      for medical and science students, including continuing professional development
      and transferable skills.

PMID- 22360627
TI  - Tissue factor-positive monocytes in children with sickle cell disease:
      correlation with biomarkers of haemolysis.
AB  - Tissue Factor (TF) initiates thrombin generation, and whole blood TF (WBTF) is
      elevated in sickle cell disease (SCD). We sought to identify the presence of TF
      positive monocytes in SCD and their relationship with the other coagulation
      markers including WBTF, microparticle-associated TF, thrombin-antithrombin (TAT)
      complexes and D-dimer. Whether major SCD-related pathobiological processes,
      including haemolysis, inflammation and endothelial activation, contribute to the
      coagulation abnormalities was also studied. The cohort comprised children with
      SCD (18 HbSS, 12 HbSC, mean age 3.6 years). We demonstrated elevated levels of TF
      positive monocytes in HbSS, which correlated with WBTF, TAT and D-dimer (P = 0.02
      to P = 0.0003). While TF-positive monocytes, WBTF, TAT and D-dimer correlated
      with several biomarkers of haemolysis, inflammation and endothelial activation in
      univariate analyses, in multiple regression models the haemolytic markers
      (reticulocytes and lactate dehydrogenase) contributed exclusively to the
      association with all four coagulant markers evaluated. The demonstration that
      haemolysis is the predominant operative pathology in the associated perturbations
      of coagulation in HbSS at a young age provides additional evidence for the early
      use of therapeutic agents, such as hydroxycarbamide to reduce the haemolytic
      component of this disease.

PMID- 22360629
TI  - IDH mutation detection in formalin-fixed paraffin-embedded gliomas using
      multiplex PCR and single-base extension.
AB  - Isocitrate dehydrogenase (IDH) genes are mutated in a significant portion of
      gliomas, myeloid leukemias and chondroid neoplasms. In gliomas, IDH mutations are
      prognostic, as those tumors with the mutation are associated with a proneural
      subclass and have longer survival compared with those without the mutation. We
      developed a simple, PCR-based SNaPshot(r) assay (Life Technologies, Carlsbad, CA,
      USA) to detect IDH1/2 mutations. This protocol combines a single, multiplexed PCR
      reaction using gene specific primers followed by a single, multiplexed SNaPshot
      reaction and detection by capillary electrophoresis. In a blinded study of 32
      paraffin-embedded glioma specimens previously screened for IDH mutations by a
      PCR/direct sequencing method, concordance of our IDH SNaPshot test with
      sequencing was 100%. We performed the assay on an additional 57 specimens
      submitted for diagnostic IDH mutation evaluation. Data analysis was much faster
      and easier to perform than analysis of the sequencing data, and results could be
      obtained in 1 day from DNA extraction to analysis. Furthermore, we could readily
      identify a mixture of 5% mutant allele vs. 95% wild-type allele in our SNaPshot
      assay, in comparison to approximately 20% mutant allele in our PCR-sequencing
      assay. Our assay represents a fast, sensitive, straightforward method of reliably
      detecting common mutations of IDH genes in glial neoplasms, or other tumors.

PMID- 22360631
TI  - Possible harmful effect of implantable cardioverter-defibrillator (ICD) lead
      placement on tricuspid valve function.

PMID- 22360635
TI  - Processing and utilization of palm date fruits for edible applications.
AB  - The date palm tree (Phoenix dactylifra L., family: Palmaceae) is perhaps the
      oldest and most important fruit crop in the Middle East and North Africa. From
      this region, the tree spread to other parts of the world and is cultivated in
      some parts of USA. About 6-7 Million tons of date fruits, belonging to a large
      variety of cultivars with different characteristics, are produced annually. The
      date fruit is mainly composed of sugars (invert sugars and/or sucrose) and fiber
      and, as such, can find a wide range of applications. However, processing
      applications of the date fruits are limited and new possibilities need to be
      exploited. This paper reviews the state-of-art knowledge on the compositional and
      technological aspects and patents pertinent to the processing and utilization of
      date fruits.

PMID- 22360636
TI  - Frequency of antibodies to Toxoplasma gondii in stray dogs of Oaxaca, Mexico.
AB  - We studied the frequency of antibodies against Toxoplasma gondii in stray dogs in
      the city of Oaxaca, Mexico through the evaluation of 154 sera by indirect ELISA.
      A frequency of 61.7% was found; it was higher in males (45 of 65, 69.2%) than in
      females (49 of 89, 55.0%), although this difference was not statistically
      significant. An increase in frequency was observed with age, the lowest being
      among animals younger than 1 yr (4 of 20, 20.0%) and the highest in dogs older
      than 7 yr (21 of 25, 84.0%). This is the first study in dogs of this region of
      Mexico and revealed high T. gondii transmission and evidence of early exposure in
      animals that are in close contact with contaminated water or raw meat, or both.
      Further studies are needed in order to understand the role of T. gondii infection
      in public health.

PMID- 22360637
TI  - Hydrogels for protein delivery.

PMID- 22360638
TI  - Plant genes involved in harbouring symbiotic rhizobia or pathogenic nematodes.
AB  - The establishment and development of plant-microorganism interactions involve
      impressive transcriptomic reprogramming of target plant genes. The symbiont
      (Sinorhizobium meliloti) and the root knot-nematode pathogen (Meloidogyne
      incognita) induce the formation of new root organs, the nodule and the gall,
      respectively. Using laser-assisted microdissection, we specifically monitored, at
      the cell level, Medicago gene expression in nodule zone II cells, which are
      preparing to receive rhizobia, and in gall giant and surrounding cells, which
      play an essential role in nematode feeding and constitute the typical root
      swollen structure, respectively. We revealed an important reprogramming of
      hormone pathways and C1 metabolism in both interactions, which may play key roles
      in nodule and gall neoformation, rhizobia endocytosis and nematode feeding.
      Common functions targeted by rhizobia and nematodes were mainly down-regulated,
      whereas the specificity of the interaction appeared to involve up-regulated
      genes. Our transcriptomic results provide powerful datasets to unravel the
      mechanisms involved in the accommodation of rhizobia and root-knot nematodes.
      Moreover, they raise the question of host specificity and the evolution of plant
      infection mechanisms by a symbiont and a pathogen.

PMID- 22360639
TI  - Cycloartane and friedelane triterpenoids from the leaves of Caloncoba glauca and
      their evaluation for inhibition of 11beta-hydroxysteroid dehydrogenases.
AB  - Five new triterpenoids, caloncobic acids A and B (1 and 2), caloncobalactones A
      and B (3 and 4), and glaucalactone (5), along with the known compounds
      3beta,21beta-dihydroxy-30-nor-(D:A)-friedo-olean-20(29)-en-27-oic acid (6) and
      acetyltrichadenic acid B (7), were isolated from the leaves of Caloncoba glauca.
      The structures of 1-5 were elucidated using spectroscopic methods. Compounds 1-7
      were evaluated for their inhibitory activities against two isozymes of 11beta
      hydroxysteroid dehydrogenase (11beta-HSD1 and 11beta-HSD2). Compounds 1 and 2
      exhibited strong inhibitory activities against mouse (EC(50) 132 and 13 nM) and
      human (EC(50) 105 and 72 nM) 11beta-HSD1.

PMID- 22360640
TI  - Solid-state NMR studies of form I of atorvastatin calcium.
AB  - Solid-state (13)C, (19)F, and (15)N magic angle spinning NMR studies of Form I of
      atorvastatin calcium are reported, including chemical shift tensors of all
      resolvable carbon sites and fluorine sites. The complete (13)C and (19)F chemical
      shift assignments are given based on an extensive analysis of (13)C-(1)H HETCOR
      and (13)C-(19)F HETCOR results. The solid-state NMR data indicate that the
      asymmetric unit of this material contains two atorvastatin molecules. A possible
      structure of Form I of atorvastatin calcium (ATC-I), derived from solid-state NMR
      data and density functional theory calculations of various structures, is
      proposed for this important active pharmaceutical ingredient (API).

PMID- 22360641
TI  - Uranium and thorium hydride complexes as multielectron reductants: a combined
      neutron diffraction and quantum chemical study.
AB  - The unusual uranium reaction system in which uranium(4+) and uranium(3+) hydrides
      interconvert by formal bimetallic reductive elimination and oxidative addition
      reactions, [(C(5)Me(5))(2)UH(2)](2) (1) ? [(C(5)Me(5))(2)UH](2) (2) + H(2), was
      studied by employing multiconfigurational quantum chemical and density functional
      theory methods. 1 can act as a formal four-electron reductant, releasing H(2) gas
      as the byproduct of four H(2)/H(-) redox couples. The calculated structures for
      both reactants and products are in good agreement with the X-ray diffraction data
      on 2 and 1 and the neutron diffraction data on 1 obtained under H(2) pressure as
      part of this study. The interconversion of the uranium(4+) and uranium(3+)
      hydride species was calculated to be near thermoneutral (~-2 kcal/mol).
      Comparison with the unknown thorium analogue, [(C(5)Me(5))(2)ThH](2), shows that
      the thorium(4+) to thorium(3+) hydride interconversion reaction is endothermic by
      26 kcal/mol.

PMID- 22360643
TI  - Association between obesity and asthma in Japanese preschool children.
AB  - Obesity may increase the risk of subsequent asthma. We have previously reported
      that there is a clear association between obesity and asthma in Japanese school
      aged children. To evaluate whether a similar association exists in younger
      children, a nationwide cross-sectional questionnaire-based survey was performed
      focusing on children aged 4-5 yr. A child who had experienced wheezing during the
      past 12 months and had ever been diagnosed with asthma by a physician was defined
      as having current asthma. Overweight and underweight were defined as BMI >=90th
      percentile and <=10th percentile, respectively, according to the reference values
      for Japanese children from 1978 to 1981. After excluding 2547 children because of
      incomplete data, 34,699 children were analyzed. Current asthma was significantly
      more prevalent in overweight children compared with underweight and normal weight
      children (13.2% for overweight vs. 10.5% for underweight and 11.1% for normal
      weight; both p < 0.001). Even after adjusting for other variables, such as
      gender, other coexisting allergic diseases, and parental history of asthma, there
      was an association between overweight and current asthma (adjusted odds ratio:
      1.23, 95% CI: 1.10-1.38, p < 0.001). Even in preschool children, obesity is
      already associated with asthma, and there was no gender effect on this
      association. Physicians should consider the impact of obesity when managing
      asthma in younger children.

PMID- 22360642
TI  - Neural mechanisms mediating contingent capture of attention by affective stimuli.
AB  - Attention is attracted exogenously by physically salient stimuli, but this effect
      can be dampened by endogenous attention settings, a phenomenon called "contingent
      capture." Emotionally salient stimuli are also thought to exert a strong
      exogenous influence on attention, especially in anxious individuals, but whether
      and how top-down attention can ameliorate bottom-up capture by affective stimuli
      is currently unknown. Here, we paired a novel spatial cueing task with fMRI to
      investigate contingent capture as a function of the affective salience of bottom
      up cues (face stimuli) and individual differences in trait anxiety. In the
      absence of top-down cues, exogenous stimuli validly cueing targets facilitated
      attention in low-anxious participants, regardless of affective salience. However,
      although high-anxious participants exhibited similar facilitation following
      neutral exogenous cues, this facilitation was completely absent following
      affectively negative exogenous cues. Critically, these effects were contingent on
      endogenous attentional settings, such that explicit top-down cues presented
      before the appearance of exogenous stimuli removed anxious individuals'
      sensitivity to affectively salient stimuli. fMRI analyses revealed a network of
      brain regions underlying this variability in affective contingent capture across
      individuals, including the fusiform face area (FFA), posterior ventrolateral
      frontal cortex, and SMA. Importantly, activation in the posterior ventrolateral
      frontal cortex and the SMA fully mediated the effects observed in FFA,
      demonstrating a critical role for these frontal regions in mediating attentional
      orienting and interference resolution processes when engaged by affectively
      salient stimuli.

PMID- 22360644
TI  - Increase in circulating endothelial progenitor cells predicts response in
      patients with advanced non-small-cell lung cancer.
AB  - Previous reports have shown that circulating endothelial progenitor cells (CEPs)
      are released in response to cytotoxic chemotherapy. We investigate the
      relationship between the kinetics of CEPs during one cycle of chemotherapy and
      the response to cytotoxic chemotherapy and prognostic impacts. Previously
      untreated patients (n = 38) receiving cytotoxic chemotherapy for non-small-cell
      lung cancer were included. Blood sampling was carried out on day 1, day 8, and
      just before the second cycle of chemotherapy. The mononuclear cell fraction was
      analyzed for CEPs by FACS analysis. We evaluated the relationship between the
      kinetics of CEPs, each independent clinicopathological variable, the response to
      chemotherapy, and the risk factors associated with prognosis. On the eighth day
      after chemotherapy, a significant decrease in CEPs was observed. In contrast, CEP
      counts before the second cycle of chemotherapy were significantly increased. The
      high percentage change in CEPs between day 1 and before the second cycle of
      chemotherapy is an independent predictive factor for response to chemotherapy.
      However, the change in CEP levels did not predict progression-free survival.
      These findings indicate that the late release of CEPs is a common phenomenon
      after chemotherapeutic treatment. The correlation with clinical response to
      chemotherapy provides further support for the biologic relevance of these cells
      in patients' prognosis and highlights the potential use of CEPs as therapeutic
      targets.

PMID- 22360645
TI  - Phosphate removal model: an observational study of low-flux dialyzers in
      conventional hemodialysis therapy.
AB  - Precise assessing phosphate removal by hemodialysis (HD) is important to improve
      phosphate control in patients on maintenance HD. We reported a simple noninvasive
      model to estimate phosphate removal within a 4-hour HD. One hundred sixty-five
      patients who underwent HD 4 hours per session using low-flux dialyzers made of
      polysulfone (1.2 m(2)) or triacetate (1.3 m(2)) were enrolled. Blood flows varied
      from 180 to 300 mL/min. Effluent dialysate samples were collected during the 4
      hour HD treatment to measure the total phosphate removal. Predialysis levels of
      serum phosphate, potassium, hematocrit, intact parathyroid hormone, total carbon
      dioxide (TCO(2)), alkaline phosphatase, clinical and dialysis characteristics
      were obtained. One hundred thirty-five observations were randomly selected for
      model building and the remaining 30 for model validation. Total amount of
      phosphate removal within the 4-hour HD was mostly 15-30 mmol. A primary model
      (model 1) predicting total phosphate removal was Tpo(4)  = 79.6 * C(45) (mmol/L) 
      0.023 * age (years) + 0.065 * weight (kg) - 0.12 * TCO(2) (mmol/L) + 0.05 *
      clearance (mL/min) - 3.44, where C(45) was phosphate concentration in spent
      dialysate measured at the 45 minute of HD and clearance was phosphate clearance
      of dialyzer in vitro conditions offered by manufacturer's data sheet. Since the
      parameter TCO(2) needed serum sample for measurement, we further derived a
      noninvasive model (model 2):Tpo(4)  = 80.3 * C(45)  - 0.024 * age + 0.07 * weight
      + 0.06 * clearance - 8.14. Coefficient of determination, root mean square error,
      and residual plots showed the appropriateness of two models. Model validation
      further suggested good and similar predictive ability of them. This study derived
      a noninvasive model to predict phosphate removal. It applies to patients treated
      by 4-hour HD under similar conditions.

PMID- 22360646
TI  - Sale of raw milk in northern Italy: food safety implications and comparison of
      different analytical methodologies for detection of foodborne pathogens.
AB  - The safety of raw milk sold in Northern Italy was investigated in relation to
      hygiene quality parameters and presence of Salmonella spp., Listeria
      monocytogenes, thermotolerant Campylobacter, and Verocytotoxin producing
      Escherichia coli O157:H7. The performance of different analytical methods used
      official culture method (ISO), modified Bacteriological Analytical Manual
      cultural method (mBAM), and polymerase chain reaction (PCR)-was evaluated. The
      presence of Mycobacterium avium subsp. paratuberculosis (Map) was investigated
      only by PCR. All samples met regulations for alkaline phosphatase and inhibitory
      substance, while 18% and 44.8% of samples collected from vending machines had,
      respectively, somatic cell count (SCC) >300,000/mL and total bacterial count
      (TBC) >50,000 CFU/mL. The correlation between hygienic quality parameters in
      samples collected from bulk tank and vending machines showed a significant
      increase of TBC in vending machines meaning that raw milk was mishandled during
      distribution and sale. All pathogens investigated were detected in raw milk sold
      at vending machines; a total of five samples (5%) had at least one pathogen, of
      which two were detected by PCR and three by mBAM. None of the samples was
      positive by cultural ISO methods. Even if the comparison of analytical methods
      showed that none performs significantly better than the others, testing a higher
      volume of milk (25 versus 210 mL) affects significantly the detection rate of
      pathogens. Three samples (3%) were positive for Map, suggesting that raw milk is
      a significant source of Map exposure for consumers. The observed TBC increase and
      the detection of several pathogenic bacteria pose questions on the safety of raw
      milk; the use of ISO seems inefficient in detecting a low contamination level of
      pathogens in milk and consequently not appropriate as official method for
      testing. In order to ensure consumer's safety, a new approach for the raw milk
      chain is required.

PMID- 22360647
TI  - Highly selective indium mediated allylation of unprotected pentosylamines.
AB  - A straightforward functionalization of D-pentoses is reported, which affords
      homoallylaminopolyols in two steps and uses ion exchange chromatography as the
      only purification operation. The key indium-mediated allylation is effected on
      unprotected glycosylamines and occurs with good to excellent syn stereoselection.
      Validation of the synthetic utility of the method was exemplified by a 3-step
      synthesis of an optically active 1,2,3,6-tetrahydropyridine from D-xylose.

PMID- 22360648
TI  - Association of MBL2 gene exon 1 variants with autoimmune thyroid disease in
      Brazilian patients.
AB  - We investigated the association between MBL2 gene exon 1 functional polymorphisms
      and autoimmune thyroid disease (AITD) in 163 Brazilian patients (87 with
      Hashimoto thyroiditis, HT; 76 with Graves' disease) and 214 healthy controls.
      Individuals carrying MBL2 O allele are at higher risk of developing AITD (OR =
      1.58, 95% CI: 1.11-2.26; P-value = 0.009) and HT (OR = 1.67, 95% CI: 1.09-2.55; P
      value = 0.013) as suggesting a possible role for mannose-binding lectin in
      influencing disease susceptibility.

PMID- 22360649
TI  - Usability of a new electronic assistive device for community-dwelling persons
      with mild dementia.
AB  - OBJECTIVE: To evaluate a newly developed integrated digital prosthetic, the
      COGKNOW Day Navigator (CDN), to support persons with mild dementia in their daily
      lives, with memory, social contacts, daily activities and safety. METHODS: A user
      participatory method was applied in the development process, which consisted of
      three iterative 1-year cycles with field tests in Amsterdam, Belfast and Lulea.
      In the successive cycles 16, 14 and 12 persons with dementia and their carers
      participated. Data on usability were collected by means of interviews,
      observations, questionnaires, logging and diaries. The CDN prototype consists of
      a touch screen, a mobile device, sensors and actuators. RESULTS: The evaluation
      showed that persons with dementia and carers valued the CDN overall as user
      friendly and useful. Conclusions regarding the effectiveness of the system in
      daily life were limited due to insufficient duration of the testing period caused
      by delays in development and some instability of the final prototype. CONCLUSION:
      With the suggested adaptations, the CDN is expected to be a useful tool for
      supporting community-dwelling persons with mild dementia and their carers.

PMID- 22360651
TI  - Development and delivery of clinical pharmacology in regulatory agencies.
AB  - Medicines regulation is based on a foundation of science, policy and judgement.
      It operates within several frameworks (scientific, legal and public health),
      which are interdependent. While safety, quality and efficacy remain the criteria
      by which medicines are assessed, the benefit-to-harm balance for any medicine or
      medical device is of paramount importance. While the regulator was hitherto the
      gatekeeper who allowed a medicine on to the market, payers now require, in
      addition, assessment of cost and clinical effectiveness before use. As regulatory
      frameworks develop, several changes will occur, as follows: (i) formal benefit
      harm assessment will become an integral part of submission for marketing
      authorizations; (ii) there will be greater use of surveillance for adverse
      reactions to new medicines using methods other than voluntary reporting; (iii)
      risk management plans will become benefit-risk management plans; (iv) life-saving
      medicines will be approved earlier; and (v) regulation and health technology
      assessment will take place simultaneously. Clinical pharmacologists will play
      important roles in these developments.

PMID- 22360652
TI  - The potential of the internet.
AB  - The internet and the World Wide Web have changed the ways that we function. As
      technologies grow and adapt, there is a huge potential for the internet to affect
      drug research and development, as well as many other aspects of clinical
      pharmacology. We review some of the areas of interest to date and discuss some of
      the potential areas in which internet-based technology can be exploited.
      Information retrieval from the web by health-care professionals is common, and
      bringing evidence-based medicine to the bedside affects the care of patients. As
      a primary research tool the web can provide a vast array of information in
      generating new ideas or exploring previous research findings. This has
      facilitated systematic reviewing, for example. The content of the web has become
      a subject of research in its own right. The web is also widely used as a research
      facilitator, including enhancement of communication between collaborators,
      provision of online research tools (such as questionnaires, management of large
      scale multicentre trials, registration of clinical trials) and distribution of
      information. Problems include information overload, ignorance of early data that
      are not indexed in databases, difficulties in keeping web sites up to date and
      assessing the validity of information retrieved. Some web-based activities are
      viewed with suspicion, including analysis by pharmaceutical companies of drug
      information to facilitate direct-to-consumer advertising of novel
      pharmaceuticals. Use of these technologies will continue to expand in often
      unexpected ways. Clinical pharmacologists must embrace internet technology and
      include it as a key priority in their research agenda.

PMID- 22360653
TI  - Imaging diagnosis--nasofrontal suture exostosis in a horse.
AB  - A 14-year-old Quarter Horse had chronic facial swelling and a more recent history
      of progressive bilateral epiphora. Radiographic findings were compatible with
      exostosis of the nasofrontal suture. Computed tomography (CT) of the head,
      including CT dacryorhinocystography, confirmed the diagnosis and allowed
      presurgical planning of resection of the exostosis, which resulted in resolution
      of the clinical signs.

PMID- 22360654
TI  - Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in nodular
      lymphocyte-predominant Hodgkin lymphoma.
AB  - The pathological background in nodular lymphocyte predominant Hodgkin lymphoma
      (NLPHL) consists of lymphocytes and histocytes. This study analysed the
      peripheral blood absolute lymphocyte count/absolute monocyte count ratio at
      diagnosis (ALC/AMC-DX) on the impact of survival in NLPHL. One hundred and three
      consecutive NLPHL patients that were followed at Mayo Clinic from 1974 to 2010
      were included in the study. Receiver operating characteristic and area under the
      curve were used for ALC/AMC-DX cut-off value analysis and proportional-hazards
      models were used to compare survival based on the ALC/AMC-DX ratio. With a median
      follow-up of 8.9 years (range: 0.3-31 years), an ALC/AMC-DX >=2.1 was the best
      cut-off value for survival with an area under the curve of 0.82, a sensitivity of
      70% and specificity of 84%. After adjusting for the International Prognostic
      Score (IPS), ALC/AMC-DX remained an independent prognostic factor for overall
      survival [Hazard Ratio (HR), 0.33, 95% confidence interval (CI), 0.15-0.71%, P <
      0.004]; lymphoma-specific survival (HR, 0.05; 95%CI, 0.01-0.68%, P < 0.002);
      progression-free survival (HR, 0.30; 95%CI, 0.14-0.60%, P < 0.006), and time to
      progression (HR, 0.06, 95%CI, 0.04-0.30%, P < 0.004). ALC/AMC-DX is a low cost,
      already standarized, biomarker to predict clinical outcomes in NLPHL.

PMID- 22360656
TI  - Determinants of the shape of emotion intensity profiles.
AB  - It has been shown that variability in the shape of emotion intensity profiles can
      be described in terms of three functional features, namely steepness at onset,
      skewness and number of peaks. However, it remains unclear which factors account
      for variability in each of these features. In the present study participants were
      asked to report intensity profiles of positive and negative emotions on a daily
      basis. Information was further collected regarding potential determinants of the
      functional features of the intensity profiles at three levels: trait-, episode-,
      and moment-determinants. Regarding steepness at onset, it was found for positive
      and negative emotions that intensity profiles have an especially explosive start
      when the eliciting stimulus is important, when the stimulus is still present
      during the beginning of the episode, and, in case of positive emotions, when the
      participant is an extravert. Concerning skewness, it was found for positive and
      negative emotions that profiles reach their peak more often towards the end when
      the eliciting stimulus is important, when the stimulus is absent during the
      beginning of the episode but present towards the end, and, in case of negative
      emotions, when the stimulus is uncontrollable. Regarding the number of peaks, it
      was found that profiles more often have multiple peaks when the eliciting
      stimulus is absent during the middle of the emotional episode.

PMID- 22360657
TI  - Variant ventricular tachycardia.

PMID- 22360658
TI  - Androgen deprivation causes truncation of the C-terminal region of androgen
      receptor in human prostate cancer LNCaP cells.
AB  - The androgen receptor (AR) acts as a ligand-dependent transcription factor,
      whereas mutant AR lacking the C-terminal ligand-binding domain functions in a
      ligand-independent manner. In the present study we report that the C-terminal
      truncated AR, which we named AR-NH1 (the N-terminal fragment of AR cleaved in the
      neighborhood of helix 1 of the ligand-binding domain), is produced in LNCaP
      prostatic carcinoma cells. The AR-NH1 of ~90 kDa was observed in an androgen
      independent LNCaP subline and was further accumulated by the proteasome inhibitor
      MG132. MG132 treatment caused the accumulation of AR-NH1 even in parent LNCaP
      cells. AR-NH1 was produced in the absence of ligand or in the presence of the AR
      antagonist bicalutamide, whereas AR agonists suppressed its production. AR-NH1
      was detected with different AR antibodies recognizing amino acid residues 1-20
      and 300-316 and was also generated from exogenous AR. Both siRNA-mediated AR
      knockdown and treatment with a serine protease inhibitor (4-(2-aminoethyl)
      benzenesulfonyl fluoride) reduced AR-NH1 levels. According to the predicted
      cleavage site (between amino acid residues 660-685) and its nuclear localization,
      it is assumed that AR-NH1 functions as a constitutively active transcription
      factor. These data suggest that AR-NH1 is produced under hormone therapy and
      contributes to the development of castration-resistant prostate cancer due to its
      ligand-independent transcriptional activity.

PMID- 22360659
TI  - Salt induced lamellar to bicontinuous cubic phase transitions in cationic
      nanoparticles.
AB  - The development of improved methods to allow the low energy production of cubic
      phase forming nanoparticles (cubosomes) is highly desired. The lamellar to
      hexagonal and cubic phase change of these lipid nanoparticles has previously been
      induced via the lowering of pH and the addition of calcium ions to anionic lipid
      nanoparticles. We have developed a method to produce low polydispersity cubosomes
      without the requirement of high energy input such as shear, sonication or
      homogenization under physiological conditions. We have found that the simple
      addition of phosphate buffered saline solution to aqueous dispersions of cationic
      liposome vesicles made with phytantriol results in the spontaneous formation of
      cubosomes after vortex mixing. This finding demonstrates the potential of
      utilizing this technique to incorporate shear and temperature sensitive compounds
      into cubosomes under extremely mild conditions for biomedical and
      nanotechnological applications.

PMID- 22360660
TI  - Time is glucose, can't miss gestational diabetes.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse
      perinatal outcomes, if not treated. International guidelines recommend screening
      "all or high-risk women" at the initial prenatal visit, when a fasting plasma
      glucose (FPG) between 92 and 126 mg/dL is diagnostic for GDM. However, glucose
      testing may be affected by a great pre-analytical variability (usually
      overlooked), due to, for example, kind of sample (serum/plasma), temperature of
      storage, time between blood draw and centrifugation (in-tube glycolysis), and use
      of a glycolysis inhibitor. So GDM may be easily missed. We aimed to evaluate the
      potential characteristics of this important issue. SUBJECTS AND METHODS: FPG was
      tested by both "routine" and "gold standard" protocols in 60 women at the first
      trimester of gestation, presenting for GDM screening. "Routine" blood plasma was
      collected in a tube with sodium fluoride, kept at room temperature, centrifuged,
      and tested 30-45 min after blood draw. "Gold standard" was a specimen from the
      same blood sample that was centrifuged within 5 min and tested together with the
      "routine" specimen. RESULTS: In the "routine" protocol, 10 mg/dL on average was
      lost for each determination. Thirteen cases of GDM and two of overt diabetes (FPG
      >126 mg/dL) were missed in this preliminary series. CONCLUSIONS: The risk for GDM
      underdiagnosis in the first half of pregnancy appears to be actual and wide. A
      closer collaboration between clinicians and pathologists is critical, allowing a
      stricter adherence to the laboratory guidelines to be ensured.

PMID- 22360661
TI  - Configurational reassignment and improved preparation of the competitive IL-6
      receptor antagonist 20R,21R-epoxyresibufogenin-3-formate.
AB  - 20R,21R-Epoxyresibufogenin-3-formate (1) and 20S,21S-epoxyresibufogenin-3-formate
      (2) were synthesized from commercial resibufogenin (3) using known procedures.
      The major product (1) was dextrorotatory, as was the major product from the
      reported synthesis of epoxyresibufogenin-3-formate; however, the literature (+)
      compound was assigned the 20S,21S-configuration on the basis of NMR data. We have
      now unequivocally determined, using single-crystal X-ray structure analyses of
      the major and minor products of the synthesis and of their derivatives, that the
      major product from the synthesis was (+)-20R,21R-epoxyresibufogenin-3-formate
      (1). Our minor synthetic product was determined to have the (-)-20S,21S
      configuration (2). The (+)-20R,21R-compound 1 has been found to have high
      affinity for the IL-6 receptor and to act as an IL-6 antagonist. A greatly
      improved synthesis of 1 was achieved through oxidation of preformed resibufogenin
      3-formate. This has enabled us to prepare, from the very expensive commercial
      resibufogenin, considerably larger quantities of 1, the only known nonpeptide
      small-molecule IL-6 antagonist.

PMID- 22360662
TI  - Water oxidation catalysis: influence of anionic ligands upon the redox properties
      and catalytic performance of mononuclear ruthenium complexes.
AB  - Aiming at highly efficient molecular catalysts for water oxidation, a mononuclear
      ruthenium complex Ru(II)(hqc)(pic)(3) (1; H(2)hqc = 8-hydroxyquinoline-2
      carboxylic acid and pic = 4-picoline) containing negatively charged carboxylate
      and phenolate donor groups has been designed and synthesized. As a comparison,
      two reference complexes, Ru(II)(pdc)(pic)(3) (2; H(2)pdc = 2,6-pyridine
      dicarboxylic acid) and Ru(II)(tpy)(pic)(3) (3; tpy = 2,2':6',2"-terpyridine),
      have also been prepared. All three complexes are fully characterized by NMR, mass
      spectrometry (MS), and X-ray crystallography. Complex 1 showed a high efficiency
      toward catalytic water oxidation either driven by chemical oxidant (Ce(IV) in a
      pH 1 solution) with a initial turnover number of 0.32 s(-1), which is several
      orders of magnitude higher than that of related mononuclear ruthenium catalysts
      reported in the literature, or driven by visible light in a three-component
      system with [Ru(bpy)(3)](2+) types of photosensitizers. Electrospray ionization
      MS results revealed that at the Ru(III) state complex 1 undergoes ligand exchange
      of 4-picoline with water, forming the authentic water oxidation catalyst in situ.
      Density functional theory (DFT) was employed to explain how anionic ligands (hqc
      and pdc) facilitate the 4-picoline dissociation compared with a neutral ligand
      (tpy). Electrochemical measurements show that complex 1 has a much lower
      E(Ru(III)/Ru(II)) than that of reference complex 2 because of the introduction of
      a phenolate ligand. DFT was further used to study the influence of anionic
      ligands upon the redox properties of mononuclear aquaruthenium species, which are
      postulated to be involved in the catalysis cycle of water oxidation.

PMID- 22360663
TI  - Cost-effectiveness of using an extensively hydrolysed formula compared to an
      amino acid formula as first-line treatment for cow milk allergy in the UK.
AB  - OBJECTIVE:   To estimate the cost-effectiveness of using an extensively
      hydrolysed formula (eHF; Nutramigen) compared with an amino acid formula (AAF;
      Neocate) as first-line treatment for cow milk allergy (CMA) in the UK, from the
      perspective of the National Health Service (NHS). METHOD:   A decision model was
      constructed depicting the treatment paths and associated resource use
      attributable to first-line management of CMA with the two formulae. The model was
      based on the case records of 145 AAF-treated infants and 150 matched eHF-treated
      patients from The Health Improvement Network (THIN) database [a nationally
      representative database of patients registered with general practitioners (GPs)
      in the UK]. The model estimated the costs and consequences of patient management
      over 12 months following their initial GP visit for CMA. RESULTS:   Patients
      presenting with a combination of gastrointestinal symptoms and eczema accounted
      for 44% of all patients in both groups. Those with gastrointestinal symptoms
      alone and eczema alone accounted for up to a further 39% and 13%, respectively.
      Those with urticaria and faltering growth accounted for <5% and <=6% of all
      patients, respectively. Patients' age and weight at presentation was a mean 2.6
      2.8 months and 4.4 kg, respectively. It took a mean 2.2 months to start a formula
      after initially seeing a GP. Time to symptom resolution following the start of
      treatment was 1.2 months in both groups; hence, the mean number of symptom-free
      months during the 12 months following the initial GP visit was estimated to be
      8.6 months in both groups. Patients treated with an eHF had a mean 13.1 GP visits
      over the 12 months compared to 17.5 visits made by AAF-treated patients (p <
      0.001). The NHS cost of managing a CMA infant over the first 12 months following
      initial presentation to a GP was estimated to be L1853 and L3161 for an eHF
      treated and AAF-treated patient, respectively. CONCLUSION:   Starting treatment
      for CMA with an eHF was the cost-effective option, as there were no significant
      differences in clinical outcomes between the two groups. A prospective,
      randomized controlled trial would allow a definitive confirmation of these
      findings.

PMID- 22360664
TI  - Photolytic and radiolytic oxidation of humic acid.
AB  - The reactions of Br(2)(-), Br, HO and N(3) with Aldrich humic acid (AHA) were
      investigated. The Br/Br(2)(-) radicals were obtained in flash-photolysis
      experiments (lambda(exc) = 266 nm) performed with NaS(2)O(8) solutions in the
      presence of bromide ions. HO and N(3) radicals were generated by pulse radiolysis
      of N(2)O-saturated solutions. From the combination of a bilinear analysis and
      computer simulations of the absorbance traces, it was possible to obtain
      information on the rate constants for the reactions of Br(2)(-), Br, HO and N(3)
      with AHA and on the intermediate species involved in the mechanism. Evidence for
      the participation of phenoxyl radicals (lambda(max) = 410 nm) is given.

PMID- 22360665
TI  - Risk factors for alcohol-related problems among victims of partner violence.
AB  - Despite the high prevalence of alcohol-related problems and disorders among women
      who experience intimate partner violence (IPV), factors related to current
      alcohol use are understudied. We examined current risk factors for alcohol
      related problems among 143 substance-using, IPV-exposed women recruited from an
      urban community from 2007 to 2010. Posttraumatic stress disorder (PTSD) symptom
      severity was associated with alcohol-related problems and a positive alcohol
      screen; physical IPV severity was related to alcohol dependence. Post hoc
      analyses revealed that PTSD symptom severity mediated relationships between
      physical IPV severity and hazardous, harmful, and dependent drinking. Focusing on
      managing PTSD symptoms and physical IPV in community-based interventions may halt
      the progression from alcohol use to dependence.

PMID- 22360666
TI  - Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and
      antioxidant status in diabetic rats.
AB  - Diabetes mellitus, which is associated with oxidative damage, has a significant
      impact on health, quality of life, and life expectancy. An ethanol extract of 
      Gymnema sylvestre  leaf was examined in vitro and in vivo to investigate the role
      of antioxidants in diabetic rats. The extract exhibited strong antioxidant
      activity in the assays, including TBA (56%), SOD-like (92%), and ABTS (54%).
      Blood glucose levels in the diabetic rats fed G. sylvestre extract decreased to
      normal levels. The presence of the antihyperglycemic compounds gymnemagenin and
      gymnemic acids in G. sylvestre extract was detected by LC/MS analysis. Lipid
      peroxidation levels were decreased by 31.7% in serum, 9.9% in liver, and 9.1% in
      kidney in the diabetic rats fed the extract. Feeding G. sylvestre extract to the
      diabetic rats decreased the activity of glutathione peroxidase in cytosolic liver
      and glutamate pyruvate transaminase in serum to normal levels.

PMID- 22360667
TI  - Editorial: a new era for medicinal chemistry.

PMID- 22360668
TI  - Two possibilities how to increase the efficacy of antidotal treatment of nerve
      agent poisonings.
AB  - Highly toxic organophosphorus inhibitors of acetylcholinesterase referred as
      nerve agents are considered to be among the most dangerous chemical warfare
      agents. The oximes represent very important part of medical countermeasures of
      nerve agent poisonings. They are used to reactivate the nerve agent-inhibited
      acetylcholinesterase. Despite long-term research activities, there is no single,
      broad-spectrum oxime suitable for the antidotal treatment of poisoning with all
      organophosphorus agents. There are two approaches how to increase and broaden the
      effectiveness of antidotal treatment of poisoning with nerve agents - to develop
      new structural analogues of currently available oximes and/or to combine
      currently available or newly developed oximes. The review describes the
      evaluation of the potency of newly developed oximes (especially the oxime K203)
      or combinations of oximes to reactivate nerve agent-inhibited
      acetylcholinesterase and to counteract the acute toxicity of nerve agents in
      comparison with single commonly used oxime (obidoxime, trimedoxime or HI-6).

PMID- 22360669
TI  - Efficacy of gemifloxacin for the treatment of experimental Staphylococcus aureus
      keratitis.
AB  - PURPOSE: The objective of the present study was to evaluate the effectiveness of
      topically applied gemifloxacin for the treatment of experimental Staphylococcus
      aureus keratitis in a rabbit model. METHODS: Rabbit corneas were intrastromally
      injected with ~100 colony-forming units (CFU) of S. aureus ATCC25923. Eight hours
      (early treatment) or 16 h (late treatment) after the injection, 1 topical drop of
      balanced salt solution (BSS), gemifloxacin ophthalmic solution (0.5%),
      levofloxacin ophthalmic solution (0.5%), or gatifloxacin eye gel (0.3%) was
      applied to each eye every 15 min for 5 doses and then, every 30 min for 14 doses.
      The eyes were examined both before and after treatment. The corneas were
      harvested from treated and untreated rabbits for the quantitation of bacteria and
      histological observation. RESULTS: In the early-treatment groups, all 3
      fluoroquinolones significantly lowered the clinical severity of infection and the
      median erosion area of the cornea compared with the BSS control (P=0.000). In the
      late-treatment groups, gemifloxacin and levofloxacin did not cause a significant
      reduction in clinical scores compared with the BSS control (P=0.107 and 0.531,
      respectively), but the gatifloxacin caused a significant reduction in clinical
      scores compared with the BSS control (P=0.011). The median erosion area
      significantly decreased with treatment with gemifloxacin, gatifloxacin, and
      levofloxacin in both early- and late-treatment groups, when compared with the
      control group (P<=0.022). In the early-treatment groups, the gemifloxacin,
      gatifloxacin, and levofloxacin groups had significantly lower CFU recovered from
      the corneas compared with the control group (P<0.01), while in the late-treatment
      groups, levofloxacin failed to reduce the CFU recovered from the corneas compared
      with the control group (P=0.695). The minimal inhibitory concentrations for
      gemifloxacin, gatifloxacin, and levofloxacin against S. aureus ATCC25923 were
      0.0625, 0.0625, and 0.125 mg/L, respectively. CONCLUSIONS: Gemifloxacin, similar
      to gatifloxacin and levofloxacin, can significantly lower the clinical severity
      and CFU per cornea observed in S. aureus keratitis when early treatment is
      implemented. Significantly, gemifloxacin showed a significant efficacy
      improvement in reducing the bacterial load recovered from the corneas in the late
      treatment experiment.

PMID- 22360670
TI  - Pivotal role of anthranilate dioxygenase genes in the adaptation of Burkholderia
      multivorans ATCC 17616 in soil.
AB  - In our recent screen for soil-induced genes, the expression of andA operon
      (andAcAdAbAa) for anthranilate catabolism in Burkholderia multivorans ATCC 17616
      was found to increase dramatically in a soil sample (Nishiyama et al., Environ
      Microbiol 12: 2539, 2010). The operon was preceded by andR encoding a putative
      transcriptional regulator for the andA operon. In this study, the andA promoter
      was induced by tryptophan and anthranilate in an andR-dependent manner. The andA
      promoter in a deletion mutant lacking tryptophan dioxygenase (one of enzymes for
      the catabolism of tryptophan to anthranilate) did not respond to tryptophan,
      indicating that not tryptophan but anthranilate is the effector of AndR. Although
      both anthranilate and tryptophan were under the detection levels in the soil
      sample, andA promoter showed higher activity in the soil sample than in a
      laboratory medium. Such induction required andR and was moderately dependent on
      the ferric uptake regulator (Fur). The proliferation ability of andAc mutant in
      the sterile soil was low compared with the co-incubated wild-type cells. These
      findings suggested that in the soil environment, anthranilate dioxygenase genes
      are induced by AndR and Fur, and play a pivotal role in the proliferation in the
      soil environment.

PMID- 22360671
TI  - 'She might have what I have got': the potential utility of vignettes as an
      indirect measure of awareness in early-stage dementia.
AB  - OBJECTIVES: In early-stage dementia, awareness at the meta-representational level
      involving a person's appraisal of his/her own condition and its implications has
      usually been assessed by interview, but contextual factors may influence
      responding. We examined the utility of an indirect, vignette-based method of
      eliciting awareness. METHOD: Three vignettes describing early-stage dementia,
      established dementia and healthy ageing were used to elicit views of the problem
      and the kinds of advice that might be helpful for the characters depicted.
      Responses were obtained from 91 people with early-stage Alzheimer's, vascular or
      mixed dementia, 87 carers and 80 older controls. For the participants with
      dementia, awareness was assessed in separate in-depth interviews and rated on a
      five-point scale for comparison purposes. RESULTS: Participants with dementia
      were often able to correctly identify the problems described in the vignettes,
      although scoring lower than carers or controls. Participants with dementia were
      also able to offer advice for those depicted, although to a lesser extent than
      carers or controls. Ability to offer advice was greater where MMSE scores were
      higher. For participants with dementia, vignette scores were moderately
      correlated with ratings derived from interviews, and those showing limited or no
      awareness offered fewer items of advice than those showing some or good
      awareness. In addition, 29% of participants with dementia spontaneously pointed
      out similarities between their own condition and that of the person depicted.
      CONCLUSIONS: The vignette method may be useful where resources preclude the use
      of in-depth interviews, and may supplement in-depth interviews as part of a multi
      dimensional assessment of awareness.

PMID- 22360673
TI  - Synthesis of a liphagal-frondosin C hybrid and speculation on the biosynthesis of
      the frondosins.
AB  - A hypothesis for the biosynthesis of the frondosins A-E is presented. Synthesis
      of a liphagal-frondosin C hybrid molecule has been achieved, with the frondosin C
      6-7-5-6 ring system being constructed by a photochemical process that follows an
      intramolecular Paterno-Buchi reaction/fragmentation pathway.

PMID- 22360674
TI  - Developing and delivering clinical pharmacology in pharmaceutical companies.
AB  - The challenges of developing new medicines are well known. Effective application
      of clinical pharmacology expertise is vital to the successful evaluation of
      potential new medicines. In drug development, this depends on effective
      integration of diverse skills. Many of these are currently in short supply, but
      through innovative partnerships between industry and academia there is an
      opportunity to reinvigorate the discipline by nurturing these key skills to the
      benefit of both partners. Specific areas of focus should be experimental
      medicine, modelling and simulation, and translational skills.

PMID- 22360675
TI  - L carnitine in hemodialysis patients.
AB  - Carnitine, 3-hydroxy-4-trimethylaminobutyrate, a small, water soluble molecule
      that is essential for mitochondrial fatty acid oxidation, is significantly
      reduced in hemodialysis patients. Uremia-induced carnitine deficiency, which is
      magnified by dialysis, is associated with symptoms or clinical problems such as
      anemia hyporesponsive to erythropoietin, cardiovascular diseases, and muscle
      weakness. This review examines studies dealing with the different clinical
      aspects of chronic renal failure patients in which carnitine deficiency may play
      a role and has also examined the studies, which have evaluated the effect of
      carnitine deficiency treatment. The reports reviewed in this study, including
      those more recent from our laboratory, have provided data suggesting that chronic
      renal failure and particularly hemodialysis patients can benefit from carnitine
      treatment in particular for renal anemia, insulin sensitivity, and protein
      catabolism. On the other hand, the heterogeneous clinical response to carnitine
      therapy in dialysis patients, reported by other studies, and the lack of large
      scale randomized trials are the rationale for the reluctance regarding a
      widespread use of carnitine supplements in dialysis patients. Well-designed
      randomized clinical trials are therefore required to fully address the
      potentially important carnitine treatment in dialysis patients.

PMID- 22360676
TI  - A critical review of the development of face recognition: experience is less
      important than previously believed.
AB  - Historically, it has been argued that face individuation develops very slowly,
      not reaching adult levels until adolescence, with experience being the driving
      force behind this protracted improvement. Here, we challenge this view based on
      extensive review of behavioural and neural findings. Results demonstrate
      qualitative presence of all key phenomena related to face individuation (encoding
      of novel faces, holistic processing effects, face-space effects, face-selective
      responses in neuroimaging) at the earliest ages tested, typically 3-5 years of
      age and in many cases even infancy. Results further argue for quantitative
      maturity by early childhood, based on an increasing number of behavioural studies
      that have avoided the common methodological problem of restriction of range, as
      well as event-related potential (ERP), but not functional magnetic resonance
      imaging (fMRI) studies. We raise a new possibility that could account for the
      discrepant fMRI findings-namely, the use of adult-sized head coils on child-sized
      heads. We review genetic and innate contributions to face individuation (twin
      studies, neonates, visually deprived monkeys, critical periods, perceptual
      narrowing). We conclude that the role of experience in the development of the
      mechanisms of face identification has been overestimated. The emerging picture is
      that the mechanisms supporting face individuation are mature early, consistent
      with the social needs of children for reliable person identification in everyday
      life, and are also driven to an important extent by our evolutionary history.

PMID- 22360677
TI  - Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S
      ICD: design and rationale of the EFFORTLESS S-ICD Registry.
AB  - BACKGROUND: Leads in and on the heart of the transvenous implantable cardioverter
      defibrillator (ICD) form the Achilles' heel of this system due to potential for
      peri- and postimplant complications. The S-ICD is a newer generation of the ICD
      that does not require leads on the heart or in the vasculature. We present the
      rationale and study design of the Evaluation oF FactORs ImpacTing CLinical
      Outcome and Cost EffectiveneSS of the S-ICD (EFFORTLESS S-ICD) Registry which was
      designed to evaluate the long-term performance of the S-ICD including patient
      quality of life and long-term resource utilization. METHODS: The Registry is an
      observational, nonrandomized, standard of care evaluation to be conducted at
      approximately 50 investigational centers in Europe and New Zealand where the S
      ICD is approved for use and distribution. Clinical Registry endpoints include
      perioperative (30 days postimplant) complication-free rate, 360-day complication
      free rate, and percentage of inappropriate shocks for atrial fibrillation and
      supraventricular ventricular tachyarrhythmia. Other endpoints include patient
      reported outcomes (e.g., quality of life) and hospital personnel implant and
      follow-up experience with the S-ICD system. CONCLUSIONS: Results from EFFORTLESS
      will build on and expand the initial published experience with the S-ICD, which
      demonstrated that the device successfully and consistently detects and treats
      episodes of sustained ventricular tachyarrhythmias. The Registry will also
      evaluate the patients' perspective of how it is to live with an S-ICD as compared
      to a contemporary transvenous system and track the experience of implanting
      physicians and personnel performing patient follow-up with a completely
      subcutaneous system.

PMID- 22360678
TI  - Free graft foreskin anoplasty.
AB  - AIM: Reconstruction of a stenotic anal canal and repair of a stenotic perineal
      colostomy using a free graft foreskin. METHOD: The use of free graft foreskin
      anoplasty was described by Freeman for the treatment of mucosal prolapse in
      pediatric patients. The original surgical technique was modified and employed in
      two adult patients for the reconstruction of the anal region. RESULTS: The graft,
      in both cases, took well with a satisfactory functional and morphological
      recovery of the anal canal. CONCLUSION: Free graft foreskin anoplasty, has proved
      to be an effective solution to stenosis in the anal canal following major local
      surgery.

PMID- 22360679
TI  - Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase
      and allogeneic hematopoietic stem cell transplantation.
AB  - We conducted a retrospective Japan-Korea multicenter study to better elucidate
      the clinicopathologic features and therapeutic modalities for aggressive natural
      killer cell leukemia (ANKL). A total of 34 patients were analyzed. The median age
      of the patients was 40 years. Among the patients in the study, four had a history
      of Epstein-Barr virus-related disorders. Three types of ANKL cells were
      categorized according to their morphological features. Leukemic cells were below
      20% in both peripheral blood and bone marrow of 11 patients. The clinical
      characteristics and prognoses of these 11 patients did not differ significantly
      from those of the others. As an initial therapy, l-asparaginase chemotherapy
      resulted in a better response. A total of six patients received allogeneic
      hematopoietic stem cell transplantation (HSCT) and two received autologous HSCT,
      with all in non-complete remission (CR). After HSCT, four with allogeneic and one
      with autologous HSCT reached CR. Median survival of all patients was 51 days.
      Median survival for the patients with and without HSCT were 266 and 36 days,
      respectively. A total of two patients with allogeneic HSCT were alive and in CR.
      All patients without HSCT died of ANKL. The use of L-asparaginase was indicated
      as a factor for longer survival (HR 0.33, 95% confidence interval; 0.13-0.83, P =
      0.02). Early diagnosis of ANKL, l-asparaginase-based chemotherapy and allogeneic
      HSCT might lead to improved patient outcomes.

PMID- 22360680
TI  - Porphyrin-cellulose nanocrystals: a photobactericidal material that exhibits
      broad spectrum antimicrobial activity.
AB  - Towards our overall objectives of developing potent antimicrobial materials to
      combat the escalating threat to human health posed by the transmission of surface
      adhering pathogenic bacteria, we have investigated the photobactericidal activity
      of cellulose nanocrystals that have been modified with a porphyrin-derived
      photosensitizer (PS). The ability of these previously synthesized porphyrin
      cellulose-nanocrystals (CNC-Por (1)) to mediate bacterial photodynamic
      inactivation was investigated as a function of bacterial strain, incubation time
      and illumination time. Despite forming an insoluble suspension, CNC-Por (1)
      showed excellent efficacy toward the photodynamic inactivation of Acinetobacter
      baumannii, multidrug-resistant Acinetobacter baumannii (MDRAB) and methicillin
      resistant Staphylococcus aureus (MRSA), with the best results achieving 5-6 log
      units reduction in colony forming units (CFUs) upon illumination with visible
      light (400-700 nm; 118 J cm(-2)). CNC-Por (1) mediated the inactivation of
      Pseudomonas aeruginosa, although at reduced activity (2-3 log units reduction).
      Confocal laser scanning microscopy of CNC-Por (1) after incubation with A.
      baumannii or S. aureus suggested a lack of internalization of the PS. Research
      into alternative materials such as CNC-Por (1) may lead to their application in
      hospitals and healthcare-related industries wherein novel materials with the
      capability of reducing the rates of transmission of a wide range of bacteria,
      particularly antibiotic resistant strains, are desired.

PMID- 22360681
TI  - Isolation and preliminary characterization of amino acid substitution mutations
      that increase the activity of the osmoregulated ProP protein of Salmonella
      enterica serovar Typhimurium.
AB  - In Enterobacteriaceae, the ProP protein, which takes up proline and glycine
      betaine, is subject to a post-translational control mechanism that increases its
      activity at high osmolarity. In order to investigate the osmoregulatory mechanism
      of the Salmonella enterica ProP, we devised a positive selection for mutations
      that conferred increased activity on this protein at low osmolarity. The
      selection involved the isolation of mutations in a proline auxotroph that
      resulted in increased accumulation of proline via the ProP system in the presence
      of glycine betaine, which is a competitive inhibitor of proline uptake by this
      permease. This selection was performed by first-year undergraduates in two
      semesters of a research-based laboratory course. The students generated sixteen
      mutations resulting in six different single amino acids substitutions. They
      determined the effects of the mutations on the growth rates of the cells in media
      of high and low osmolarity in the presence of low concentrations of proline or
      glycine betaine. Furthermore, they identified the mutations by DNA sequencing and
      displayed the mutated amino acids on a putative three-dimensional structure of
      the protein. This analysis suggested that all six amino acid substitutions are
      residues in trans-membrane helices that have been proposed to contribute to the
      formation of the transport pore, and, thus, may affect the substrate binding site
      of the protein.

PMID- 22360682
TI  - Lack of association between TLR4 rs4986790 polymorphism and risk of
      cardiovascular disease in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with
      increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates
      the innate immune response via NF-kB pathway and mitogen-activated protein kinase
      signaling, leading to expression of proinflammatory cytokines and chemokines. The
      G allele of TLR4 rs4986790 (+896A>G, Asp299Gly) gene polymorphism has been
      implicated in reduction of risk of atherosclerosis. In this study, 1481 RA
      patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were
      genotyped for the rs4986790 TLR4 variant to determine the influence of this
      variant in the risk of CV events in these patients. Also, HLA-DRB1 status was
      determined using molecular based methods. Moreover, potential influence of
      rs4986790 variant in the development of subclinical atherosclerosis was assessed
      in a subgroup of RA patients with no history of CV events by the measurement of
      surrogate markers of subclinical atherosclerosis. No statistically significant
      differences in allele or genotype frequencies for the rs4986790 variant between
      RA patients who experienced CV events or not were found. Likewise, no significant
      association between this gene variant and any of the surrogate markers of
      subclinical atherosclerosis was found. In summary, results in our study do not
      support the hypothesis that the rs4986790 (+896A>G, Asp299Gly) TLR4 variant may
      influence predisposition for subclinical atherosclerosis and clinically evident
      CV disease in RA patients.

PMID- 22360684
TI  - Preliminary evaluation of serial (18) FDG-PET/CT to assess response to toceranib
      phosphate therapy in canine cancer.
AB  - Palladia(TM)  (toceranib phosphate-Pfizer Animal Health) is a novel orally
      administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of
      canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor
      growth, progression, and metastasis. Toceranib's targets include vascular
      endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth
      factor receptor, and kit. Positron Emission Tomography/Computed Tomography
      (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to
      antineoplastic therapy in human patients. In this study, serial PET/CT imaging
      with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to
      toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing
      dogs underwent tumor assessment using both standard RECIST criteria and PET/CT
      prior to and at a median of 5 weeks postinitiation of toceranib treatment.
      Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with
      subsequent modifications based on observed toxicity. Treatment was continued in
      patients achieving stable disease with acceptable drug tolerance. One dog was
      maintained on drug despite dose modification due to toxicity; measurable clinical
      and image-based responses were seen after 10 weeks of therapy. All others had
      stable or progressive disease based on clinical restaging and PET/CT at first
      recheck. . Due to discordance with anatomic and metabolic imaging, further
      studies are needed to investigate the role of molecular imaging in assessment of
      drug response and identify other potential molecular targets of toceranib.

PMID- 22360685
TI  - Protection of CDC25 phosphatases against oxidative stress in breast cancer cells:
      evaluation of the implication of the thioredoxin system.
AB  - Reactive oxygen species regulate protein functionality. Cell cycle CDC25
      phosphatases are targets of such oxidative regulation in vitro. We sought to
      evaluate if a thioredoxin (trx)-dependent redox regulation of CDC25 exists in
      cancer cells. For that purpose, we used MCF7 and MDA-MB 231 breast cancer cells,
      which express trx1 differentially, together with two trx/thioredoxin reductase
      (trxR) inhibitors, Auranofin and Acrolein. Auranofin could induce a full trxR
      inhibition associated with ROS production in both cell lines. Acrolein could
      provoke similar effects only in MDA-MB 231 cells with a low trx1 expression.
      Simultaneous trx1 oxidation and trxR inactivation occurred only in the presence
      of Acrolein and resulted in a G2-M cell cycle arrest, without full CDC25
      inhibition in MDA-MB 231 cells. Our data suggest that the maintenance of CDC25
      activity does not fully rely on the trx system in breast cancer cells, even in
      the presence of a major oxidative stress.

PMID- 22360686
TI  - Antimicrobial metabolites from the Paracel Islands sponge Agelas mauritiana.
AB  - Four new alkaloids, (-)-8'-oxo-agelasine D (2), ageloxime B (3), (+)-2-oxo
      agelasidine C (4), and 4-bromo-N-(butoxymethyl)-1H-pyrrole-2-carboxamide (5), and
      the known compound (-)-ageloxime D (1) were isolated from the marine sponge
      Agelas mauritiana. Their chemical structures were established on the basis of
      spectroscopic analysis. Compounds 1 and 3 both showed antifungal activity against
      Cryptococcus neoformans and antileishmanial activity against Leishmania donovani
      in vitro. Compound 3 also exhibited antibacterial activity against Staphylococcus
      aureus and methicillin-resistant S. aureusin vitro.

PMID- 22360687
TI  - Management of autoimmune diseases after haematopoietic stem cell transplantation.
AB  - Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) is an
      option for the treatment of malignant and non-malignant diseases, including the
      severe autoimmune diseases. Intriguingly, the 'new' autoimmunity developing after
      transplantation is a constantly recognized phenomenon, which has to be
      differentiated from original disease relapse, toxicity, infection and graft
      versus-host disease. The reported autoimmune diseases occurring in this setting
      are mainly antibody-associated and organ-specific, with scarce evidence in
      support for specific treatment options. This review focuses on current concepts
      on the pathogenesis, the available data on incidence, risk factors,
      manifestations and treatment of post-HSCT autoimmune diseases.

PMID- 22360688
TI  - Investigation of in situ oxalate formation from 2,3-pyrazinedicarboxylate under
      hydrothermal conditions using nuclear magnetic resonance spectroscopy.
AB  - We have investigated the assembly of a two-dimensional coordination polymer,
      Nd(2)(C(6)H(2)N(2)O(4))(2)(C(2)O(4))(H(2)O)(2), that has been prepared from the
      hydrothermal reaction of Nd(NO(3))(3).6H(2)O and 2,3-pyrazinedicarboxylic acid
      (H(2)pzdc). In situ oxalate formation as observed in this system has been been
      investigated using (1)H and (13)C nuclear magnetic resonance spectroscopy, and a
      pathway for C(2)O(4)(2-) anion formation under hydrothermal conditions has been
      elucidated. The oxalate ligands found in
      Nd(2)(C(6)H(2)N(2)O(4))(2)(C(2)O(4))(H(2)O)(2) result from the oxidation of
      H(2)pzdc, which proceeds through intermediates, such as 2-pyrazinecarboxylic acid
      (2-pzca), 2-hydroxyacetamide, 3-amino-2-hydroxy-3-oxopropanoic acid, 2
      hydroxymalonic acid, 2-oxoacetic acid (glyoxylic acid), and glycolic acid. The
      species are generated through a ring-opening that occurs via cleavage of the C-N
      bond of the pyrazine ring, followed by hydrolysis/oxidation of the resulting
      species.

PMID- 22360690
TI  - Preparational effects on the excitation energy transfer in the FMO complex.
AB  - Using numerically exact path integral Monte Carlo simulations, the excitation
      energy transfer in the Fenna-Matthews-Olson (FMO) complex is determined at room
      temperature. The employed system and environment parameters are based on
      previously reported atomistic simulations. When starting with excitations
      localized at specific chromophores, no coherence features can be observed. In
      contrast, when starting with delocalized excitations, traces of coherent motion
      become apparent. On the one hand, as experimental findings account for much
      stronger quantum coherent motion, these results suggest a reevaluation of the
      underlying spectral densities. On the other hand, the results emphasize that the
      initial preparation of the excitonic system needs to be taken into account
      carefully when attempting to reproduce the respective experiments.

PMID- 22360689
TI  - From basic to clinical neuropharmacology: targetophilia or pharmacodynamics?
AB  - Historically, much drug discovery and development in psychopharmacology tended to
      be empirical. However, over the last 20 years it has primarily been target
      oriented, with synthesis and selection of compounds designed to act at a specific
      neurochemical site. Such compounds are then examined in functional animal models
      of disease. There is little evidence that this approach (which we call
      'targetophilia') has enhanced the discovery process and some indications that it
      may have retarded it. A major problem is the weakness of many animal models in
      mimicking the disease and the lack of appropriate biochemical markers of drug
      action in animals and patients. In this review we argue that preclinical studies
      should be conducted as if they were clinical studies in design, analysis, and
      reporting, and that clinical pharmacologists should be involved at the earliest
      stages, to help ensure that animal models reflect as closely as possible the
      clinical disease. In addition, their familiarity with pharmacokinetic
      pharmacodynamic integration (PK-PD) would help ensure that appropriate dosing and
      drug measurement techniques are applied to the discovery process, thereby
      producing results with relevance to therapeutics. Better integration of
      experimental and clinical pharmacologists early in the discovery process would
      allow observations in animals and patients to be quickly exchanged between the
      two disciplines. This non-linear approach to discovery used to be the way
      research proceeded, and it resulted in productivity that has never been bettered.
      It also follows that occasionally 'look-see' studies, a proven technique for drug
      discovery, deserve to be reintroduced.

PMID- 22360693
TI  - Allergic diseases and respiratory symptoms in urban and rural children in Grodno
      Region (Belarus).
AB  - BACKGROUND: Because of the unknown frequency of asthma and other common allergic
      diseases in children living in Belarus, we conducted a population-based
      respiratory health survey. The objective of the study was to estimate the
      prevalence of allergic diseases and major allergic symptoms in children of the
      Grodno Region (Western Belarus) and to examine their familial and environmental
      correlates. METHODS: The cross-sectional study was conducted in 2010 and included
      2606 urban and 2422 rural children aged 6-16 years. Physician-diagnosed
      respiratory diseases and symptoms were ascertained using the ISAAC questionnaire
      completed by the parents. Both family and environmental factors were examined for
      their association with respiratory health outcomes including asthma and spastic
      bronchitis. Descriptive statistics and multiple logistic regression analysis were
      used to test associations. RESULTS: The prevalence of asthma, atopic eczema and
      allergic rhinitis was 1.39%, 10.25%, and 3.84%, respectively. Spastic bronchitis
      was reported for 6.74% of children. Chronic respiratory symptoms occurring in the
      past 12 months and suggestive of asthma included chest wheeze (9.71%) attacks of
      dyspnea at rest (1.77%), symptoms of hay fever (2.45%) attacks of sneezing and
      nasal congestion without a cold (6.78%), and recurrent itchy rash (13.48%). All
      diseases except for asthma and spastic bronchitis as well as symptoms of hay
      fever, congested nose and itchy rash were more frequent in urban than in rural
      children (p < 0.05). Results of multivariate logistic analysis confirmed
      associations (p < 0.05) between asthma and parental asthma (OR = 4.82) and
      dampness in home (OR = 2.12) after adjustment for age, gender and place of
      residence. Spastic bronchitis in children who did not have a concurrent diagnosis
      of asthma was related (p < 0.05) to parental asthma (OR = 2.18), dampness in the
      home (OR = 1.68) and less use of coal-based heating (OR = 0.64). Allergic
      rhinitis and atopic eczema were associated (p < 0.05) with parental asthma (OR =
      5.07 and OR = 1.91, respectively), dampness (OR = 2.33 and OR = 1.51,
      respectively), lower parental education (OR = 0.74 and OR = 0.68, respectively)
      and household density (OR = 0.84 and OR = 0.92), respectively. CONCLUSIONS: The
      findings show a low prevalence of allergic diseases and symptoms in children of
      Western Belarus, following similar East-West gradients described in the
      literature. All allergic disorders except asthma were less frequent in the rural
      population. A very low prevalence of childhood asthma and the possibility of
      underdiagosis of the disease in the surveyed population deserve further
      investigation.

PMID- 22360692
TI  - Heat-shock proteins attenuate SERCA inactivation by the anti-apoptotic protein
      Bcl-2: possible implications for the ER Ca2+-mediated apoptosis.
AB  - We have demonstrated previously that Bcl-2 and Bcl-2Delta21, a C-terminally
      truncated Bcl-2 sequence, inactivate SERCA (sarcoplasmic/endoplasmic reticulum
      Ca(2+)-ATPase) 1 in isolated SR (sarcoplasmic reticulum), accompanied by a
      translocation from CRDs (caveolae-related domains) of the SR. In the present
      study, we obtained evidence for the interaction of Bcl-2 with SERCA2b in C2C12
      myoblasts and HEK (human embryonic kidney)-293 cells. Bcl-2 and SERCA2b co
      immunoprecipitated from lysate and microsomal fractions of Bcl-2-overexpressing
      cells. However, Bcl-2 overexpression resulted only in a slight translocation from
      the CRDs and no significant SERCA inactivation. In isolated HEK-293 cell
      microsomes, incubation with Bcl-2Delta21 afforded SERCA2b inactivation and some
      translocation. HSP (heat-shock protein) 70, HSP90, HSP27 and alpha-crystallin
      attenuated Bcl-2Delta21-dependent SERCA2b inactivation. An in vitro mechanistic
      study with the SERCA1 isoform shows that HSP70 (i) protects SERCA1 from the
      inactivation by Bcl-2Delta21, (ii) inhibits SERCA1 translocation from CRD
      fractions, and (iii) prevents the Bcl-2Delta21-dependent loss of FITC labelling.
      Our data demonstrate that the mechanism of SERCA inactivation by Bcl-2
      established in vitro for the SERCA1 isoform can be extended to the main
      housekeeping SERCA2b isoform, and that functional interactions of SERCA2b and Bcl
      2 in the cell may be modulated by HSP70 and other chaperones and stress-regulated
      proteins.

PMID- 22360694
TI  - Risk factors for smoking in rural women.
AB  - BACKGROUND: This study examined the association between social, demographic, and
      psychologic factors and smoking status among Appalachian Ohio women. A secondary
      aim examined whether specific factors could be identified and segmented for
      future tailored treatment of tobacco dependence. METHODS: A cross-sectional
      survey (n=570) obtained information about social, demographic, and psychologic
      factors and smoking. Logistic regression described associations between these
      characteristics and smoking status. Chi-square automatic interaction detection
      (CHAID) analyses identified subgroups at risk for smoking. RESULTS: Fifty-two
      percent never smoked, with 20.5% and 27.5% categorized as former and current
      smokers, respectively. Women with low adult socioeconomic position (SEP) were
      more likely to smoke (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.74
      5.34) compared to high SEP women. Other factors associated with current smoking
      included age 31-50 (OR 2.30, 95% CI 1.22-4.33), age 18-30 (OR 3.29, 95% CI 1.72
      5.34), Center for Epidemiologic Studies Depression scale (CES-D) score>=16 (OR
      1.99, 95% CI 1.31-3.05), and first pregnancy at age<20 (OR 1.74, 95% CI 1.14
      2.66). The prevalence of smoking was 50% among those with four or more risk
      factors compared to 10% for those reporting no risk factors. CHAID analyses
      identified low adult SEP and depressive symptoms as the combination of risk
      factors most strongly associated with smoking; 49.3% of women in this subgroup
      currently smoked. CONCLUSIONS: Low SEP in adulthood, maternal circumstances, and
      depressive symptoms are associated with current smoking. Tailored cessation
      interventions that address these risk factors should be developed and further
      evaluated in an attempt to reduce disparities in smoking prevalence among this
      vulnerable group of women.

PMID- 22360695
TI  - Risk of breast cancer mortality among women cohabiting with same sex partners:
      findings from the National Health Interview Survey, 1997-2003.
AB  - BACKGROUND: Lesbians and bisexual women are more likely than other women to
      evidence a unique mix of common breast cancer risk factors. It is not known if
      this results in greater breast cancer mortality risk. We investigate possible
      sexual orientation-related differences in risk for fatal breast cancer in a large
      representative U.S. sample of married and cohabiting women. METHODS: Between 1997
      and 2003, the National Health Interview Survey (NHIS) interviewed married or
      cohabiting female participants, aged 18-80 years inclusively, who reported either
      a male (n=136,174) or female (n=693) coresidential relationship partner. These
      records are linked to the National Death Index to provide information on
      mortality status as of December 31, 2006. Employing these data, we estimated the
      age-adjusted relative risk (RR) and its 95% confidence interval (CI) for
      mortality attributed to breast cancer using a Cox proportional hazard model.
      RESULTS: Women in same-sex couples, compared to women in different-sex
      relationships, had greater age-adjusted risk for fatal breast cancer (RR=3.2, CI
      1.01-10.21) but did not differ in their overall risk for mortality. CONCLUSIONS:
      Our findings provide tentative support that sexual orientation is differentially
      linked to risk of fatal breast cancer. These findings underscore the need to
      investigate further breast cancer morbidity and mortality risk among women with
      minority sexual orientation.

PMID- 22360696
TI  - Cost burden and treatment patterns associated with management of heavy menstrual
      bleeding.
AB  - OBJECTIVES: This study evaluated the healthcare resource use, work productivity
      loss, costs, and treatment patterns associated with newly diagnosed idiopathic
      heavy menstrual bleeding (HMB) using a large employer database. METHODS: Medical
      and pharmacy claims (1998-2009) from 55 self-insured U.S. companies were
      analyzed. Women aged 18-52 years with >=2 HMB claims (ICD-9 626.2, 627.0) and
      continuously enrolled for >=6 months before the first claim were matched 1:1 with
      controls. Exclusion criteria were cancer, pregnancy, and infertility; HMB-related
      uterine conditions; endometrial ablation; hysterectomy; anticoagulant
      medications; and other known HMB causes. All-cause healthcare resource use and
      costs were compared between the HMB and control cohorts using statistical methods
      accounting for matched study design. Treatment patterns were examined for HMB
      subjects. RESULTS: HMB and control cohorts (n=29,842 in both) were matched and
      balanced in baseline characteristics and costs. During follow-up, HMB subjects
      had significantly higher all-cause resource use than did control subjects:
      hospitalization incidence rate ratio (IRR)=2.70 (95% confidence interval [CI]
      2.62-2.79); emergency room visits IRR=1.35 (95% CI 1.31-1.38); outpatient visits
      IRR=1.29 (95% CI 1.29-1.30). Average annualized all-cause costs were also higher
      for HMB subjects than controls (mean difference $2,607, p<0.001). Costs
      associated with HMB claims represented 50% ($1,313) of the all-cause cost
      difference. Of HMB subjects, 63.2% underwent surgical treatment as initial
      therapy. CONCLUSIONS: In this large matched-cohort study, an idiopathic diagnosis
      of HMB was associated with high rates of surgical intervention and increased
      healthcare resource use and costs.

PMID- 22360698
TI  - Effects of home, outside leisure, social, and peer activity on psychological
      health among Japanese family caregivers.
AB  - OBJECTIVE: Previous research has indicated that informal caregivers' personal
      activities are disrupted by their caregiving role, leading to psychological
      stress and lower life satisfaction. However, the extent to which engagement in
      personal activities affects caregivers' psychological health remains unclear.
      This study examines the relationship between different types and frequencies of
      activities and both positive and negative parameters of the psychological health
      of caregivers. METHODS: A mail survey was conducted with 727 family caregivers of
      older persons using adult day-care services in the Tokyo metropolitan area.
      Perceived caregiver burden, care satisfaction, life satisfaction, and depression
      were used as psychological health outcomes. Engagement in home, outside leisure,
      social, and peer activities, as well as caregiver and care-recipient
      characteristics and caregiving situations, were assessed using a multivariate
      regression analysis. RESULTS: Engagement in home activities was related to lower
      scores on burden and depression and greater care satisfaction after controlling
      for care needs and caregiver characteristics, and social and peer activities were
      associated with greater life satisfaction. More frequent engagement was also
      associated with better psychological health, but a moderate involvement in home
      activities was most strongly associated with better care satisfaction. The amount
      of outside leisure activity was not significantly related to any of the outcomes.
      CONCLUSION: This study shows that activity type and frequency are associated with
      caregivers' psychological health, extending previous findings and providing
      practical implications for the support of family caregivers through programs to
      improve their participation in specific types of activities.

PMID- 22360699
TI  - Bacterial adhesion, intracellular survival and cytokine induction upon
      stimulation of mononuclear cells with planktonic or biofilm phase Staphylococcus
      epidermidis.
AB  - Staphylococcus epidermidis is a leading cause of hospital-acquired and biofilm
      associated infections. Interactions of peripheral blood mononuclear cells (PBMCs)
      and monocyte-derived macrophages with planktonic or biofilm phase S. epidermidis
      cells were studied. Biofilm phase bacteria exhibited higher attachment, as well
      as, a 10-fold higher intracellular survival in monocyte-derived macrophages than
      their planktonic counterparts. Stimulation of PBMCs and monocyte-derived
      macrophages was performed with live or formalin-fixed bacterial cells.
      Supernatant concentration of selected cytokines was measured by Luminex((r)) 
      xMAP(TM)  technology at different time points. As compared to planktonic phase,
      biofilm phase bacteria elicited lower amounts of proinflammatory cytokines and
      Th1 response cytokines, such as TNFalpha, IL-12p40, IL-12p70 and IFN-gamma,
      whereas they enhanced production of IL-8, GM-CSF and IL-13. This phenomenon was
      independent of formalin pretreatment. Taken together, these results may
      contribute to interpretation of observed silent course of biofilm-associated
      infections.

PMID- 22360697
TI  - Role stress, role reward, and mental health in a multiethnic sample of midlife
      women: results from the Study of Women's Health Across the Nation (SWAN).
AB  - BACKGROUND: Little is known about the independent associations of reward and
      stress within specific roles with multiple measures of mental health in an
      ethnically diverse community sample of midlife women. The objective of this study
      is to examine if (1) role reward (within each role and across roles) contributes
      directly to mental health and buffers the negative impact of role stress and (2)
      associations among role occupancy, role stress, and role reward and mental health
      vary by race/ethnicity. METHODS: With separate logistic regression analysis, we
      investigated cross-sectional relationships between role stress and role reward
      with presence/absence of high depressive symptoms (Center for Epidemiologic
      Studies Depression Scale [CES-D>=16]), anxiety symptoms (feeling tense or
      nervous, irritable or grouchy, fearful for no reason, and heart pounding or
      racing total score>=4), or low social functioning (bottom 25th percentile of the
      Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in
      the third visit of the Study of Women's Health Across the Nation (SWAN), a
      longitudinal population-based study of menopause. RESULTS: High reward across
      roles attenuated the negative impact of role stress on social functioning but not
      on anxiety or depression. High reward marriage buffered the impact of marital
      stress on depression, and high reward mothering buffered the effect of maternal
      stress on depression and social functioning. Compared to Caucasians, Hispanics
      and Chinese with high stress across roles had better social functioning, and
      African American mothers had lower odds of high depressive symptoms. CONCLUSIONS:
      Role reward buffers the negative impact of stress on social functioning and
      depression, but not on anxiety. Minorities may respond to role stress by seeking
      social support.

PMID- 22360700
TI  - The roles of clinical pharmacologists in UK universities.
AB  - Clinical pharmacologists in universities play major roles in research and
      teaching and provide important contributions to National Health Service (NHS)
      activities, such as work for research ethics, drug and therapeutics, and clinical
      governance committees. Their research extends from preclinical studies using
      drugs to understand physiology and the mechanisms of disease to large-scale
      clinical trials and population studies. This work is truly translational, with a
      focus on drugs and medicines and an emphasis on efficacy and safety. The lack of
      an organ base has allowed clinical pharmacologists to follow their interests
      wherever they lead, but their visibility has been hampered by successive earlier
      versions of the General Medical Council's Tomorrow's Doctors document, which
      undermined some of the necessary scientific underpinning of medical practice and
      reduced the time clinical pharmacologists had to interact with medical students
      and recently qualified doctors at the point of choosing their careers. Additional
      problems have arisen from the stifling effect of the European Union Clinical
      Trials Directive, and its UK interpretation, on clinical research. For future
      success, clinical pharmacologists need to embrace translational research, use
      recent changes to Tomorrow's Doctors, linked to the creation of safe prescribing
      skills, to spend more face-to-face time with their students, fight for a
      simplification and proportionate regulation of research, and persuade doctors,
      health service planners and the government of the importance of clinical
      pharmacology for UK clinical research, the NHS, patient safety and creation of
      health and wealth.

PMID- 22360701
TI  - Native chemical ligation at glutamine.
AB  - The desulfurization reaction introduced by Yan and Dawson as a postnative
      chemical ligation step greatly expanded the scope of ligation chemistry beyond
      Xaa-Cys (Xaa is any amino acid) by making ligation at Xaa-Phe, Xaa-Val, Xaa-Lys,
      Xaa-Leu, Xaa-Thr, and Xaa-Pro junctions accessible in the synthesis of functional
      proteins. A new ligation site based on Xaa-Gln utilizing gamma-mercaptoglutamine
      is reported, and several examples on the efficiency of ligation coupled with
      desulfurization are provided.

PMID- 22360702
TI  - Chemical and functional characterization of Italian propolis obtained by
      different harvesting methods.
AB  - The composition and antioxidant activity of Italian poplar propolis obtained
      using three harvesting methods and extracted with different solvents were
      evaluated. Waxes, balsams, and resins contents were determined. Flavones and
      flavonols, flavanones and dihydroflavonols, and total phenolics were also
      analyzed. To characterize the phenolic composition, the presence of 15 compounds
      was verified through HPLC-MS/MS. The antioxidant activity was evaluated through
      1,1-diphenyl-2-picrylhydrazyl radical and reducing power assays. The ability of
      propolis to inhibit lipid oxidation was monitored by analyzing hydroperoxide and
      TBARS formation in lipids incorporated into an oil-in-water (O/W) emulsion.
      Acetone shows the highest extraction capacity. Wedge propolis has the highest
      concentration of active phenolic compounds (TP = 359.1 +/- 16.3 GAEs/g; TFF =
      5.83 +/- 0.42%; TFD = 7.34 +/- 1.8%) and seems to be the most promising for
      obtaining high-value propolis more suitable to prepare high-quality dietary
      supplements (TBARS = 0.012 +/- 0.009 mmol std/g; RP = 0.77 +/- 0.07 TEs/g).

PMID- 22360703
TI  - Dilator venotomy technique for placement of hemodialysis catheter following
      recanalization of occluded central vein.
AB  - Recanalization of occluded central veins for insertion of hemodialysis catheter
      is a particular attractive option in patients who are catheter dependent for
      hemodialysis, as it delays exhaustion of conventional venous accesses. Literature
      detailing techniques for catheter placement in recanalized veins remain sparse.
      We hereby describe a safe and economical technique of using dilator venotomy to
      allow catheter placement following successful recanalization.

PMID- 22360704
TI  - Referral proformas improve compliance to national colorectal 2-week wait targets:
      does this affect cancer detection rates?
AB  - AIM: To facilitate implementation of National Institute for Health and Clinical
      Excellence (NICE) guidelines for urgent colorectal cancer referral, local cancer
      networks have promoted the use of standardized proformas in primary care. This
      clinical audit assessed use of the proforma within the Thames Valley Cancer
      Network (TVCN) to see whether increased proforma use was associated with higher
      compliance to NICE guidelines and higher cancer detection rates. METHOD: All 2
      week wait referrals for lower bowel cancer to the six Acute NHS Trusts in the
      TVCN received during the month of June 2010 were identified, anonymized and
      analysed in relation to colorectal cancer detection rates. RESULTS: Of the 586
      referrals audited, proforma usage varied significantly across the six Acute NHS
      Trusts from 18% to 96%. Referral letters from primary care had NICE compliance
      ranging from 30 to 50%. In those which received a referral protocol, 50-90% were
      NICE compliant. Proforma use was associated with higher cancer detection rates (P
      = 0.03). CONCLUSION: These results have wide-ranging implications since they
      suggest that the adoption of a simple proforma in primary care can improve the
      effectiveness of referral for suspected cancer.

PMID- 22360705
TI  - Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced
      Parkinson's disease.
AB  - BACKGROUND: Infusion of levodopa/carbidopa intestinal gel (Duodopa ; Abbott) was
      introduced in Sweden in 1991 as an experimental treatment in advanced Parkinson's
      disease and obtained EU approval in 2004. There is compelling evidence for short
      term use of this treatment; however, long-term data are scarce. METHODS: A
      retrospective review of medical records was performed. The primary objective was
      to assess the duration of treatment for all Swedish patients starting long-term
      levodopa/carbidopa gel therapy between January 1991 and June 2008. Secondary aims
      were to study demographics, treatment with anti-Parkinson's disease drugs and
      other concomitant medications, and reasons for discontinuation of
      levodopa/carbidopa gel. RESULTS: Of 150 identified patients, 135 were included in
      the study. On average, patients were 49 years at diagnosis of Parkinson's disease
      and 63 years when infusion therapy was initiated. The median treatment time on
      infusion was 3.4 years (range, 0-16 years). The restricted mean treatment time
      was nearly 8 years; 81 patients were still on treatment at the end of the study.
      Levodopa was used as monotherapy in a majority of patients. Dosage of the drug
      was stable over time. Thirty-one patients discontinued infusion prior to the
      cutoff date and 23 patients died. Device-related problems were the most common
      reason for discontinuation. Patients were more likely to discontinue infusion
      therapy before 2000. The year of infusion initiation was significantly earlier in
      the dropout group compared with a matched group of continuing patients.
      CONCLUSIONS: Levodopa/carbidopa intestinal gel infusion is a long-term treatment
      alternative in patients with advanced Parkinson's disease.

PMID- 22360706
TI  - Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549
      cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.
AB  - AIMS: Reactive oxygen species (ROS) are involved in the pathogenesis of many
      inflammatory diseases such as chronic obstructive pulmonary disease (COPD). They
      can alter the expression of genes involved in cellular damage by activating
      transcription factors, including the NF-kappaB and the activator protein 1 (AP
      1). Phosphodiesterase type 4 (PDE4) inhibitors have anti-inflammatory and
      antioxidant effects, as described in in vivo and in vitro COPD models. This study
      analysed the effects of piclamilast, a selective PDE4 inhibitor, on modulating
      the global gene expression profile in A549 cells exposed to H(2)O(2). MAIN
      METHODS: Changes in gene expression were analysed using high-density Affymetrix
      microarrays and validated by RT-PCR. Cell proliferation was studied using BrdU
      incorporation. Apoptosis was assessed by flow cytometry using annexin V
      fluorescein isothiocyanate. C-Jun phosphorylation and AP-1 activation were
      determined by ELISA and luciferase assay, respectively. KEY FINDINGS: Our results
      indicate that H(2)O(2) modified the expression of several genes related to
      apoptosis, cell cycle control and cell signalling, including IL8, FAS, HIG2,
      CXCL2, CDKN25 and JUNB. Piclamilast pre-treatment significantly inhibited the
      changes in 23 genes via mechanisms involving AP-1 activation and c-Jun
      phosphorylation at Ser63. Functional experiments confirmed our results,
      suggesting new targets related to the antioxidant properties of PDE4 inhibitors.
      SIGNIFICANCE: This is the first study to demonstrate antioxidant effects of a
      selective PDE4 inhibitor at the global gene expression level, and the results
      support the importance of AP-1 as a key regulator of the expression of genes
      involved in the inflammatory response of epithelial cells to oxidative damage.

PMID- 22360707
TI  - Restoring primacy in amnesic free recall: evidence for the recency theory of
      primacy.
AB  - Primacy and recency effects at immediate recall are thought to reflect the
      independent functioning of a long-term memory store (primacy) and a short-term
      memory store (recency). Key evidence for this theory comes from amnesic patients
      who show severe long-term memory storage deficits, coupled with profoundly
      attenuated primacy. Here we challenge this dominant dual-store theory of
      immediate recall by demonstrating that attenuated primacy in amnesic patients can
      reflect abnormal working memory rehearsal processes. D.A., a patient with severe
      amnesia, presented with profoundly attenuated primacy when using her preferred
      atypical noncumulative rehearsal strategy. In contrast, despite her severe
      amnesia, she showed normal primacy when her rehearsal was matched with that of
      controls via an externalized cumulative rehearsal schedule. Our data are in
      keeping with the "recency theory of primacy" and suggest that primacy at
      immediate recall is dependent upon medial temporal lobe involvement in cumulative
      rehearsal rather than long-term memory storage.

PMID- 22360708
TI  - Transesophageal evaluation of asymptomatic Wolff-Parkinson-White syndrome.
AB  - BACKGROUND: Risk stratification for Wolff-Parkinson-White (WPW) by intracardiac
      electrophysiology study (ICEPS) carries risks related to catheterization. We
      describe an alternative approach by using transesophageal electrophysiology study
      (TEEPS). METHODS: The pediatric electrophysiology database was reviewed for
      patients with WPW and no documented clinical supraventricular tachycardia (SVT)
      who underwent risk stratification by TEEPS from October 2005 to November 2010. Of
      those who underwent subsequent ICEPS, only those with data available to compare
      accessory pathway (AP) conduction during ICEPS and TEEPS were included. RESULTS:
      Of 65 patients who underwent TEEPS, 42 were found to have an indication for
      ablation. The most common indication for ICEPS was inducible SVT, which was
      induced in 67% of patients. Of 42 patients who underwent subsequent ICEPS, 23 had
      sufficient data for comparison of AP conduction between ICEPS and TEEPS. There
      was no difference between the baseline minimum 1:1 antegrade conduction through
      the accessory pathway found at TEEPS versus ICEPS (312 +/- 51 ms vs 316 +/- 66
      ms, P = 0.5). There was no significant difference between the baseline antegrade
      AP-effective refractory period found at TEEPS versus ICEPS (308 +/- 34 ms vs 297
      +/- 37 ms, P = 0.07). There were no complications related to TEEPS or ICEPS.
      CONCLUSION: TEEPS is a safe and feasible alternative to ICEPS for risk
      stratification in patients with asymptomatic WPW and should be considered before
      ICEPS and ablation.

PMID- 22360709
TI  - An exploration of participant experience of a communication training program for
      people with traumatic brain injury and their communication partners.
AB  - PURPOSE: To investigate the experiences of participants who attended
      communication training programs for people with traumatic brain injury (TBI) and
      their everyday communication partners (CP) as part of a non-randomised controlled
      trial. METHOD: The participants were people with TBI and their CP, who were
      family members or carers of the people with TBI. Twenty-six participants (13
      participants with TBI and 13 CP) completed the JOINT program, which involved
      participants with TBI and CP attending the program together. Fourteen
      participants with TBI completed the TBI SOLO training program, which did not
      involve the participation of a CP. Semi-structured videotaped interviews were
      completed by all participants at the end of the training. Using a six-step
      generic analysis procedure, data were categorised into topics and then subtopics
      to identify conceptually discrete units. RESULTS: Participants described
      improvements in communication skills, the impact of improved communication
      skills, valuable components of the programs and components that needed changes.
      CONCLUSION: The accounts of participants provided additional evidence for the
      effectiveness of the training programs, assisted with identifying helpful
      components of the training and demonstrated the usefulness of a qualitative
      research methodology as part of evaluating the outcomes of the clinical trial.

PMID- 22360712
TI  - Caffeic acid and ferulic acid inhibit UVA-induced matrix metalloproteinase-1
      through regulation of antioxidant defense system in keratinocyte HaCaT cells.
AB  - Ultraviolet A (UVA) plays a vital role in the pathogenesis of premature skin
      aging through keratinocyte cytotoxicity and degradation of collagen, a main
      component of the extracellular matrix providing structural support. Oxidative
      stress caused by UVA irradiation can mediate induction of matrix metalloprotease
      1 (MMP-1), a major enzyme responsible for collagen damage. Protection against UV
      mediated disturbance of antioxidant defense system has been proposed as a
      possible mechanism by which botanical compounds slow down skin aging process.
      This study therefore aimed to assess inhibitory effects of caffeic acid (CA) and
      ferulic acid (FA), powerful plant-based phenolic antioxidants, on UVA-induced
      cytotoxicity and MMP-1 activity and mRNA level through modulation of antioxidant
      defense mechanism in immortalized human keratinocyte (HaCaT) cells. Pretreatment
      of the cells with CA or FA prior to UVA irradiation inhibited cytotoxicity,
      induction of MMP-1 activity and mRNA and oxidant formation. Moreover, CA and FA
      were able to up-regulate glutathione (GSH) content, gamma-glutamate cysteine
      ligase (gamma-GCL) mRNA as well as activities and mRNA expression of catalase and
      glutathione peroxidase (GPx) in irradiated cells. In conclusion, CA and FA
      provided protective effects on UVA-mediated MMP-1 induction in HaCaT cells
      possibly through restoration of antioxidant defense system at the cellular and
      molecular level.

PMID- 22360713
TI  - Two anatomic resources of canine pelvic limb muscles based on CT and MRI.
AB  - Advances in magnetic resonance (MR) imaging and three-dimensional (3D) modeling
      software provide the tools necessary to create sophisticated, interactive
      anatomic resources that can assist in the interpretation of MR images of
      extremities, and learning the structure and function of limb musculature.
      Modeling provides advantages over dissection or consultation of print atlases
      because of the associated speed, flexibility, 3D nature, and elimination of
      superimposed arrows and labels. Our goals were to create a diagnostic atlas of
      pelvic limb muscles that will facilitate interpretation of MR images of patients
      with muscle injury and to create a 3D model of the canine pelvic limb musculature
      to facilitate anatomic learning. To create these resources, we used structural
      segmentation of MR images, a process that groups image pixels into anatomically
      meaningful regions. The Diagnostic Atlas is an interactive, multiplanar, web
      based MR atlas of the canine pelvic limb musculature that was created by manually
      segmenting clinically analogous MR sequences. Higher resolution volumetric MR and
      computed tomography (CT) data were segmented into separately labeled volumes of
      data and then transformed into a multilayered 3D computer model. The 3D Model
      serves as a resource for students of gross anatomy, encouraging integrative
      learning with its highly interactive and selective display capabilities. For
      clinicians, the 3D Model also serves to bridge the gap between topographic and
      tomographic anatomy, displaying both formats alongside, or even superimposed over
      each other. Both projects are hosted on an open-access website,
      http://3dvetanatomy.ncsu.edu/

PMID- 22360715
TI  - Direct observation of nanoparticle superlattice formation by using liquid cell
      transmission electron microscopy.
AB  - Direct imaging of nanoparticle solutions by liquid phase transmission electron
      microscopy has enabled unique in situ studies of nanoparticle motion and growth.
      In the present work, we report on real-time formation of two-dimensional
      nanoparticle arrays in the very low diffusive limit, where nanoparticles are
      mainly driven by capillary forces and solvent fluctuations. We find that
      superlattice formation appears to be segregated into multiple regimes. Initially,
      the solvent front drags the nanoparticles, condensing them into an amorphous
      agglomerate. Subsequently, the nanoparticle crystallization into an array is
      driven by local fluctuations. Following the crystallization event, superlattice
      growth can also occur via the addition of individual nanoparticles drawn from
      outlying regions by different solvent fronts. The dragging mechanism is
      consistent with simulations based on a coarse-grained lattice gas model at the
      same limit.

PMID- 22360714
TI  - Pharmacoeconomics.
AB  - Pharmacoeconomics is an essential component of health technology assessment and
      the appraisal of medicines for use by UK National Health Service (NHS) patients.
      As a comparatively young discipline, its methods continue to evolve. Priority
      research areas for development include methods for synthesizing indirect
      comparisons when head-to-head trials have not been performed, synthesizing
      qualitative evidence (for example, stakeholder views), addressing the limitations
      of the EQ-5D tool for assessing quality of life, including benefits not captured
      in quality-adjusted life years (QALYs), ways of assessing valuation methods (for
      determining utility scores), extrapolation of costs and benefits beyond those
      observed in trials, early estimation of cost-effectiveness (including mechanism
      based economic evaluation), methods for incorporating the impact of non-adherence
      and the role of behavioural economics in influencing patients and prescribers.

PMID- 22360716
TI  - Factors associated with perceived health in elderly medical inpatients: a
      particular focus on personal coping recourses.
AB  - AIM: We wanted to unveil associations between perceived health and physical
      health, function in activity of daily living, anxiety, depression and coping
      resources in terms of sense of coherence (SOC) in elderly (>=65 years) in
      hospital patients without cognitive impairment. METHOD: In a cross-sectional
      study, we evaluated 217 hospitalized elderly patients with an age range 65-95
      (mean 77.9) years. Perceived health was rated on a four-point scale. Physical
      health was measured with the Charlson index; functional status was rated using
      the Lawton and Brody's scale for self-maintaining and instrumental activities of
      daily living; and, anxiety and depression were rated using the Hospital Anxiety
      and Depression scale. Finally, the 13-item version of the SOC scale was used to
      assess coping, and cognitive state was assessed using the Mini-mental State
      Examination. RESULTS: In all, 40% of the patients reported good perceived health.
      In an adjusted logistic regression analysis, the main outcome good perceived
      health was associated with increasing age: odds ratio (OR) 1.06 (95% CI 1.01
      1.11); good physical health: OR 2.49 (95% CI 1.22-5.07); and, medium high and
      high SOC: OR 2.48 (95% CI 1.20-5.13), and OR 2.43 (95% CI 1.11-5.28),
      respectively. Explained variance was 22.2%. CONCLUSION: Good coping resources and
      low severity of co-morbid disorders are the two most important factors that
      explain why elderly inpatients rate their health as good. Since coping may be
      equally important as poor physical health for perception of health, coping should
      be recognized and measured in clinical practice.

PMID- 22360717
TI  - Chronic myeloid leukemia and risk of second malignancy in two eras of treatment.

PMID- 22360718
TI  - Staphylococcus aureus meningitis: barriers to treatment.

PMID- 22360719
TI  - Immunoglobulin G4-positive plasmablastic lymphoma.

PMID- 22360720
TI  - Leukemic transformation in patients with myelodysplastic syndromes after
      treatment with granulocyte colony-stimulating factor.

PMID- 22360722
TI  - Ir(I)/HCl catalyzed head-to-tail homocoupling reactions of vinylsilanes.
AB  - Novel homocoupling reactions of vinylsilanes, catalyzed by a mixture of Ir(I) and
      HCl, were developed. This process leads to exclusive formation of head-to-tail
      vinylsilane dimers in high yields at room temperature. Synthetic attributes of
      transformations of the resulting head-to-tail vinylsilane dimers and
      polymerization of bis(vinylsilane) were investigated.

PMID- 22360721
TI  - Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice.
AB  - The importance of PDHK (pyruvate dehydrogenase kinase) 2 and 4 in regulation of
      the PDH complex (pyruvate dehydrogenase complex) was assessed in single- and
      double-knockout mice. PDHK2 deficiency caused higher PDH complex activity and
      lower blood glucose levels in the fed, but not the fasted, state. PDHK4
      deficiency caused similar effects, but only after fasting. Double deficiency
      intensified these effects in both the fed and fasted states. PDHK2 deficiency had
      no effect on glucose tolerance, PDHK4 deficiency produced only a modest effect,
      but double deficiency caused a marked improvement and also induced lower insulin
      levels and increased insulin sensitivity. In spite of these beneficial effects,
      the double-knockout mice were more sensitive than wild-type and single-knockout
      mice to long-term fasting, succumbing to hypoglycaemia, ketoacidosis and
      hypothermia. Stable isotope flux analysis indicated that hypoglycaemia was due to
      a reduced rate of gluconeogenesis and that slightly more glucose was converted
      into ketone bodies in the double-knockout mice. The findings establish that PDHK2
      is more important in the fed state, PDHK4 is more important in the fasted state,
      and survival during long-term fasting depends upon regulation of the PDH complex
      by both PDHK2 and PDHK4.

PMID- 22360723
TI  - Right-to-left shunts as a cause of juxtacortical spots in patients with migraine.
AB  - BACKGROUNDS: Juxtacortical spots on fluid-attenuated inversion recovery (FLAIR)
      images can be frequently detected in patients with migraine. However, the origins
      of the cerebral lesions (including juxtacortical spots on FLAIR images) found in
      the previous studies are not known. We sought to investigate the association
      between juxtacortical spots on FLAIR images and right-to-left shunt (RLS) in
      migraine patients. METHODS: Juxtacortical spots on FLAIR images were arbitrarily
      defined as small areas of hyperintensities in the juxtacortex and cortico
      subcortical junction. The presence of RLS was examined by a transcranial Dopper
      (TCD) with the agitated saline test. The degree of RLS was categorized into four
      grades according to the number of microemboli: no shunt, <10 microbubbles (MB),
      >10 MB single spots pattern, and >10 MB shower/curtain pattern. We compared the
      results for migraine patients (n = 49) with those for healthy controls (n = 49).
      RESULTS: Juxtacortical spots on FLAIR images occurred in 38/98 subjects; of them,
      27/49 (55.1%) had migraines and 11/49 (22.2%) were healthy controls (P = 0.002).
      The independent factors associated with juxtacortical spots on FLAIR images were
      female, migraine patients, and RLS by multivariate analysis. In migraine
      patients, RLS was independently associated with juxtacortical spots on FLAIR
      images. CONCLUSION: Our results suggest that juxtacortical spots on FLAIR images
      were frequently found in migraine patients and might be associated with the
      presence of RLS in those patients. Further studies are needed to assess whether
      juxtacortical spots have clinical implications in patients with migraine.

PMID- 22360724
TI  - A prediction rule for food challenge outcome in children.
AB  - BACKGROUND: In children with food-related symptoms, a food challenge is
      considered as the gold standard to diagnose allergy. If food allergy could be
      predicted by patient history and/or diagnostic tests, the number of time
      consuming and sometimes risky food challenges could be decreased. We aimed to
      determine questionnaire and test-based characteristics, to predict the food
      challenge outcome (FCO) in children referred to a tertiary centre for the
      evaluation of food-related symptoms. METHODS: Pre-challenge standardized
      questionnaires, skin prick tests (SPT), and specific IgE levels (sIgE) were
      obtained in patients that underwent a food challenge in our hospital in 2009.
      Characteristics of patients with positive and negative FCO were compared, and uni
      and multivariate associations between predictors and FCO were calculated. Based
      on the multivariate model, a risk score was developed to predict the FCO.
      RESULTS: One hundred and twenty-nine challenges were analyzed, 41.9% had a
      positive outcome. Median age of both groups was 4.9 yrs (range 2.8-8.3). Patients
      with a positive FCO reacted faster with symptoms after allergen ingestion and had
      higher sIgE levels compared to children with negative FCO. A clinical risk score
      was developed based on the index food, 'time between allergen ingestion and
      complaints' and sIgE levels (range 0-10). The prognostic capacity of this model
      (AUC) was excellent (0.90). The very high- and low-risk groups (24% of patients)
      are both predicted excellent without misclassification. CONCLUSION: Positive FCO
      can be predicted by the index food, time between allergen ingestion and
      development of symptoms, and the sIgE level.

PMID- 22360725
TI  - Role of the N-terminal domain of the chaperone ClpX in the recognition and
      degradation of lambda phage protein O.
AB  - The ClpXP ATPase-protease complex is a key element of the protein quality control
      machinery in the cell. ClpX consists of a zinc-binding domain (ZBD) that forms
      dimers and a AAA(+) domain that arranges into a hexamer in an ATP-dependent
      manner. Here, we report the binding site of the ClpX substrate lambda phage
      protein O (lambdaO) on ZBD(2) in ClpX using NMR and mutagenesis analysis. lambdaO
      protein was found to interact with a hydrophobic patch on the larger surface of
      ZBD(2). The affinity of lambdaO toward ZBD(2) was investigated using a
      quantitative optical biosensor method of dual polarization interferometry. The
      data suggest overlapping binding sites of lambdaO and the ClpX cofactor SspB on
      the ZBD(2). Interestingly, a single key mutation in ZBD was found to enhance the
      ClpXP-dependent degradation of lambdaO.

PMID- 22360726
TI  - Loss of capture due to hyperkalemia: is that the whole story?

PMID- 22360727
TI  - Accent on communication: the impact of regional and foreign accent on
      comprehension in adults with aphasia.
AB  - PURPOSE: This study explored whether an unfamiliar non-native accent, differing
      in both segmental and prosodic features was more difficult for individuals with
      aphasia to understand than an unfamiliar native accent, which differed in
      segmental features only. METHOD: Comprehension, which was determined by accuracy
      judgments on true/false sentences, and speed of response were assessed in the
      following three conditions: a familiar Southern Standard British English (SSBE)
      accent, an unfamiliar native Grimsby accent, and an unfamiliar non-native Chinese
      accent. Thirty-four English speaking adults (17 people with and 17 people without
      aphasia) served as listeners for this study. RESULTS: All listeners made
      significantly more errors in the unfamiliar non-native accent, although this
      difficulty was more marked for those with aphasia. While there was no affect of
      speaker accent on the response times of listeners with aphasia, listeners without
      aphasia were significantly slower with the unfamiliar non-native accent.
      CONCLUSION: The results indicate that non-native accented speech affects
      comprehension even on simple tasks in ideal listening conditions. The findings
      suggest that speaker accent, especially accents varying in both segmental and
      prosodic features, can be a barrier to successful interactions between non-native
      accented speakers and native listeners, particularly those with aphasia.

PMID- 22360728
TI  - Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase
      2 under mild hypoxia.
AB  - The function and survival of eukaryotic cells depends on a constant and
      sufficient oxygen supply. Cells recognize and respond to hypoxia by accumulation
      of the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of an
      oxygen-sensitive HIF-1alpha and a constitutive HIF-1beta subunit. Besides
      physiology, HIF-1 induction is involved in major pathological processes such as
      cardiovascular disease, inflammation and cancer, which are associated with the
      formation of reactive oxygen species (ROS). ROS have been reported to affect HIF
      1 activity but the role for ROS in regulating HIF-1 has not been definitely
      settled. In order to shed light on the redox-regulation of HIF-1 by ROS, we
      studied the impact of exogenous ROS treatment (H(2)O(2)) on HIF-1alpha and HIF-1
      regulatory protein prolyl hydroxylase 2 (PHD2) in the human osteosarcoma cell
      line U2OS. At early reaction periods, H(2)O(2) induced HIF-1alpha but at
      prolonged observation phases the opposite occurred. Herein, modulation of PHD
      activity appeared to be the key element, because knockdown and inhibition of the
      PHD2 prevented reduction of HIF-1alpha. However, H(2)O(2) treatment constantly
      suppressed HIF-1 transactivation at all time-points. Our data indicate a dual
      redox regulation of HIF-1alpha protein amount with a constant suppression of HIF
      1 target gene expression by ROS.

PMID- 22360729
TI  - PAI-1, progress in understanding the clinical problem and its aetiology.
AB  - Plasminogen activator inhibitor-1 (PAI-1, also known as SERPINE1) is a member of
      the serine protease inhibitor (SERPIN) superfamily and is the primary
      physiological regulator of urokinase-type plasminogen activator (uPA) and tissue
      type plasminogen activator (tPA) activity. Although the principal function of PAI
      1 is the inhibition of fibrinolysis, PAI-1 possesses pleiotropic functions
      besides haemostasis. In the quarter century since its discovery, a number of
      studies have focused on improving our understanding of PAI-1 functions in vivo
      and in vitro. The use of Serpine1-deficient mice has particularly enhanced our
      understanding of the functions of PAI-1 in various physiological and
      pathophysiological conditions. In this review, the results of recent studies on
      PAI-1 and its role in clinical conditions are discussed.

PMID- 22360730
TI  - Diagnosis of Borrelia-associated uveitis in two horses.
AB  - Borrelia burgdorferi, the etiologic agent of Lyme disease is a tick born
      spirochetal infection. Clinical signs of Lyme borreliosis are uncommon in horses,
      but when present they are often vague and nonspecific. In horses, Lyme
      borreliosis has been implicated in musculoskeletal, neurological, reproductive,
      and ocular disorders, including uveitis, but definitive diagnosis can be
      challenging as the causative agent is rarely isolated and serologic tests can be
      unreliable and do not confirm active disease. Here, we report two cases of equine
      uveitis associated with B. burgdorferi based on the identification of spirochetes
      within ocular fluids and confirmed with PCR testing. The two cases illustrate
      some of the challenges encountered in the recognition and diagnosis of equine
      Lyme borreliosis. Although only one of many possible causes of equine uveitis,
      Lyme disease should be considered a differential diagnosis, especially in endemic
      areas. Given the possibility for false negative results of serum tests during
      uveitis associated with B. burgdorferi and the failure of such tests to confirm
      active infection, a combination of cytologic assessment, antibody, and/or PCR
      testing of ocular fluids may be worthwhile if the clinical suspicion for Lyme
      uveitis is high.

PMID- 22360731
TI  - Immune thrombocytopenic purpura following anti-rabies vaccines.

PMID- 22360732
TI  - Developing and delivering clinical toxicology in the UK National Health Service.
AB  - Clinical toxicology concerns the investigation, diagnosis and management of
      suspected poisoning. It is an important discipline because of the frequency of
      suspected poisoning, including drug overdose. In the UK, most episodes are
      managed by nonspecialists, with support provided online or by telephone from the
      National Poisons Information Service. Leadership and clinical support for this is
      provided by a small number of clinical toxicologists, who are almost invariably
      accredited specialists in clinical pharmacology and therapeutics. Priorities for
      maintaining and enhancing clinical toxicology as a subspeciality in the UK
      include: 1 Maintaining funding for poisons centres. This is essential in spite of
      current budgetary pressures. 2 Formal training in the discipline. The 1 year
      optional training module in clinical toxicology approved in 2011 as part of the
      clinical pharmacology and therapeutics curriculum represents important progress,
      but funding for appropriate programmes and accreditation for trainees from other
      relevant disciplines is needed. Arrangements for registration and revalidation
      are also required. 3 An improved evidence base for management of poisoning.
      Priority areas include continued surveillance of the epidemiology and outcomes of
      poisoning, including syndromic surveillance, more rapid characterization of the
      human toxicity of newly introduced medicines and better clinical evidence on use
      of antidotes and other treatments; for example, acetylcysteine and lipid emulsion
      therapy.

PMID- 22360734
TI  - Patient and proxy measurement of quality of life among general hospital in
      patients with dementia.
AB  - BACKGROUND: We aimed to investigate quality of life ratings among people with
      varying severity of dementia and their carers, recruited in general hospital.
      METHOD: We recruited 109 people with dementia, and their proxies (carers), from
      psychiatric referrals of inpatients in two general hospitals in England. From
      patients, we gathered data on quality of life (QoL-AD and EQ5-D) and depressive
      symptoms, and from proxies we gathered data on patient quality of life (Proxy QoL
      AD and EQ5-D), severity of dementia, activities of daily living, physical illness
      and depressive symptoms, and on carer stress. RESULTS: Completion rates for both
      measures were progressively lower with increasing dementia severity. Patients
      rated their quality of life more highly than proxies on Qol-AD (patients=32.2,
      CI=30.7-33.7, proxies=24.7, CI=23.8-26.0, p<0.001) and on EQ5D (patients=0.71,
      CI=0.64-0.77, proxies=0.30, CI=0.22-0.38, p<0.001). For proxy EQ5D, impaired
      instrumental ADLs (p=0.003) and more severe dementia (p=0.019) were associated
      with ratings, while for proxy QoL-AD, only more severe dementia (p=0.039) was
      associated with ratings. Lower patient EQ-5D scores were independently associated
      only with carer stress (p=0.01). Lower patient QoL-AD scores were associated with
      patient depression (p=0.001), impaired activities of daily living (p=0.02) and
      proxy psychiatric symptoms (p=0.002). CONCLUSIONS: Among patients with moderate
      to severe dementia in general hospital, proxy measures of quality of life are the
      only practical option. Patients and proxies appear to have very different
      concepts of quality of life in dementia.

PMID- 22360736
TI  - Molecular and morphological characterization of a poorly known marine ciliate,
      Myoschiston duplicatum precht 1935: implications for phylogenetic relationships
      between three morphologically similar genera -- Zoothamnium, Myoschiston, and
      Zoothamnopsis (Ciliophora, Peritrichia, Zoothamniidae).
AB  - We studied the morphology and molecular phylogeny of Myoschiston duplicatum, a
      peritrich ciliate that has been recorded as an epibiont of crustaceans, but which
      we also identified on marine algae from Korea. The important morphological
      characteristics revealed by silver staining of Myoschiston species have not been
      described because they are rarely collected. Using morphological methods, we
      redescribed the type species of the genus, Myoschiston duplicatum, and provided
      an improved diagnosis of Myoschiston. In addition, the coding regions for nuclear
      small subunit (SSU) rRNA and internal transcribed spacer 1-5.8S-internal
      transcribed spacer 2 sequences were sequenced. Phylogenetic analyses that
      included available SSU rDNA sequences of peritrichs from GenBank strongly
      supported a position of M. duplicatum within the family Zoothamniidae. In
      addition, phylogenetic analyses were performed with single datasets (ITS1-5.8S
      ITS2) and combined datasets (SSU rDNA + ITS1-5.8S-ITS2) to explore further the
      phylogenetic relationship in the family Zoothamniidae between the three
      morphologically similar genera-Zoothamnium, Myoschiston, and Zoothamnopsis.

PMID- 22360737
TI  - Pharmacoepidemiology.
AB  - Current concerns over the safety of medicines once they have been marketed mean
      that pharmacoepidemiology is of increasing importance. There are three main areas
      in which further research is needed. 1 To improve the methods used to make causal
      inference of effects of medicines and to raise the quality of the reporting and
      critical appraisal tools, so that the strengths and weaknesses of the new methods
      can be judged. 2 To apply the methods in areas where randomized trials cannot
      easily be done, such as in pregnancy. 3 To use electronic health records as fully
      as possible, using linkage between different databases, ensuring the data are of
      as high quality as possible. Public health and public perceptions mean that much
      of pharmacoepidemiology must be done using non-industry funding sources.

PMID- 22360738
TI  - Cyclopropanations of olefin-containing natural products for simultaneous arming
      and structure activity studies.
AB  - Cyclopropanations of alkene-containing natural products that proceed under mild
      conditions are reported for simultaneous arming and structure-activity
      relationship studies. An alkynyl diazo ester under Rh(II) catalysis is employed
      for cyclopropanations of electron-rich olefins while an alkynyl sulfonium ylide
      is used for electron-poor olefins. This approach enables simultaneous natural
      product derivatization for SAR studies and arming (i.e., via alkyne attachment)
      for subsequent conjugation with reporter tags (e.g., biotin, fluorophores,
      photoaffinity labels) for mechanism of action studies including cellular target
      identification and proteome profiling experiments.

PMID- 22360739
TI  - Effect of prostaglandin duration on outcomes in transposition of the great
      arteries with intact ventricular septum.
AB  - OBJECTIVE: To study the effects of duration of preoperative prostaglandin E1
      (PGE) exposure on perioperative outcomes of the arterial switch operation in
      patients with transposition of the great arteries with an intact ventricular
      septum. DESIGN: Retrospective chart review. SETTING: Pediatric cardiac intensive
      care unit in a tertiary care children's hospital. PATIENTS: All patients with
      transposition of the great arteries with an intact ventricular septum from 1995
      to 2008. OUTCOME MEASURES: Inotropic score was calculated for all patients in the
      first 5 postoperative days and maximum inotropic score was recorded. Length of
      postoperative mechanical ventilation, fluid balance, mechanical ventilation time,
      as well as intensive care unit and hospital stay were recorded for all patients.
      RESULTS: Study population included 59 patients, 41 (69%) underwent balloon atrial
      septostomy. PGE was used in 52 patients, median exposure of 59 hours, range 0 to
      272 hours. Longer preoperative PGE exposure was associated with longer
      preoperative mechanical ventilation (P < .001). There was no association between
      preoperative PGE duration and cardiopulmonary bypass time, cross-clamp time, or
      total hospital stay. Patients with longer preoperative PGE exposure had a lower
      postoperative inotrope score (10 vs. 15 P = .02). CONCLUSION: Greater
      preoperative PGE exposure was associated with prolonged preoperative mechanical
      ventilation. Longer PGE exposure was associated with lower postoperative inotrope
      requirements. Aggressive efforts to avoid or shorten PGE infusion duration may
      not be warranted in this population.

PMID- 22360740
TI  - The role of trust in the use of health infomediaries among university students.
AB  - PURPOSE: This study identifies, through the extended technology acceptance model,
      the relationships among trust, information quality (IQ) and intention, as well as
      various trust levels, as they influence the behavior intention to use health
      infomediaries. METHOD: Our survey was conducted with university undergraduate
      students in March 2008. There were 274 usable responses. The survey instrument
      consisted of questions regarding demographics; information relevance,
      understandability, reliability, adequacy and usefulness; trust and behavior
      intention. Respondents were divided into two groups: a high-trust group and a low
      trust group. RESULTS: The results suggest that in the case of the high-trust
      group, trust has positive mediation effects of information relevance and
      information reliability on behavior intention. The positive mediation effects of
      information adequacy and information usefulness on behavior intention were also
      identified in the case of the low-trust group. CONCLUSION: This study expands the
      understanding of health infomediary users, including aspects of trust and IQ. It
      also suggests that an effective strategy should aim at understanding the
      conceptual difference between high and low trust and the differential mechanisms
      by which high-trust and low-trust consumer groups affect the adoption of health
      infomediaries.

PMID- 22360741
TI  - Syndromic surveillance models using Web data: the case of scarlet fever in the
      UK.
AB  - Recent research has shown the potential of Web queries as a source for syndromic
      surveillance, and existing studies show that these queries can be used as a basis
      for estimation and prediction of the development of a syndromic disease, such as
      influenza, using log linear (logit) statistical models. Two alternative models
      are applied to the relationship between cases and Web queries in this paper. We
      examine the applicability of using statistical methods to relate search engine
      queries with scarlet fever cases in the UK, taking advantage of tools to acquire
      the appropriate data from Google, and using an alternative statistical method
      based on gamma distributions. The results show that using logit models, the
      Pearson correlation factor between Web queries and the data obtained from the
      official agencies must be over 0.90, otherwise the prediction of the peak and the
      spread of the distributions gives significant deviations. In this paper, we
      describe the gamma distribution model and show that we can obtain better results
      in all cases using gamma transformations, and especially in those with a smaller
      correlation factor.

PMID- 22360742
TI  - The oligomer plasticity of the small heat-shock protein Lo18 from Oenococcus oeni
      influences its role in both membrane stabilization and protein protection.
AB  - The ability of the small Hsp (heat-shock protein) Lo18 from Oenococcus oeni to
      modulate the membrane fluidity of liposomes or to reduce the thermal aggregation
      of proteins was studied as a function of the pH in the range 5-9. We have
      determined by size-exclusion chromatography and analytical ultracentrifugation
      that Lo18 assembles essentially as a 16-mer at acidic pH. Its quaternary
      structure evolves to a mixture of lower molecular mass oligomers probably in
      dynamic equilibrium when the pH increases. The best Lo18 activities are observed
      at pH 7 when the particle distribution contains a major proportion of dodecamers.
      At basic pH, particles corresponding to a dimer prevail and are thought to be the
      building blocks leading to oligomerization of Lo18. At acidic pH, the dimers are
      organized in a double-ring of stacked octamers to form the 16-mer as shown by the
      low-resolution structure determined by electron microscopy. Experiments performed
      with a modified protein (A123S) shown to preferentially form dimers confirm these
      results. The alpha-crystallin domain of Methanococcus jannaschii Hsp16.5, taken
      as a model of the Lo18 counterpart, fits with the electron microscopy envelope of
      Lo18.

PMID- 22360743
TI  - Macroporous and monolithic anode based on polyaniline hybridized three
      dimensional graphene for high-performance microbial fuel cells.
AB  - Microbial fuel cell (MFC) is of great interest as a promising green energy source
      to harvest electricity from various organic matters. However, low bacterial
      loading capacity and low extracellular electron transfer efficiency between the
      bacteria and the anode often limit the practical applications of MFC. In this
      work, a macroporous and monolithic MFC anode based on polyaniline hybridized
      three-dimensional (3D) graphene is demonstrated. It outperforms the planar carbon
      electrode because of its abilities to three-dimensionally interface with
      bacterial biofilm, facilitate electron transfer, and provide multiplexed and
      highly conductive pathways. This study adds a new dimension to the MFC anode
      design as well as to the emerging graphene applications.

PMID- 22360744
TI  - Stampidine as a promising antiretroviral drug candidate for pre-exposure
      prophylaxis against sexually transmitted HIV/AIDS.
AB  - INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an evolving new approach to
      prevention of sexually transmitted HIV-1 that employs antiretroviral (ARV) agents
      prior to potential HIV-1 exposure in an attempt to reduce the likelihood of HIV-1
      infection postexposure. The identification of new ARV agents with potent activity
      against multidrug-resistant HIV remains an unmet and urgent challenge in the
      field of PrEP. AREAS COVERED: This article reviews the preclinical and early
      clinical activity and safety profile of stampidine, a novel antiretroviral (ARV)
      drug candidate that exhibits remarkable subnanomolar to low nanomolar in vitro
      antiretroviral potency against genotypically and phenotypically nucleoside
      reverse transcriptase inhibitor (NRTI)-resistant primary clinical HIV isolates,
      non-nucleoside RT-resistant HIV-1 isolates. Stampidine has a favorable
      pharmacokinetic profile in mice, rats, dogs and cats with 25 or 50 mg/kg
      tolerable dose levels yielding micromolar plasma concentrations that are 1000
      fold higher than its in vitro IC(50) value against HIV. Stampidine has a
      favorable, safety profile in mice, rats, dogs and cats and it showed significant
      in vivo ARV activity in HIV-infected Hu-PBL-SCID mice as well as FIV-infected
      domestic cats. Furthermore, it did not cause any maternal toxicity, developmental
      toxicity or teratogenicity in rabbits treated at 10 - 40 mg/kg/day dose levels.
      In a recently completed first-in-human Phase I clinical trial, stampidine did not
      cause dose-limiting toxicity at single dose levels ranging from 5 to 25 mg/kg.
      EXPERT OPINION: The favorable safety and activity profile of stampidine warrants
      its further development as a promising next-generation PrEP candidate to prevent
      the sexual transmission of HIV-1. The discovery of stampidine as a potent
      antiretroviral agent represents a significant step forward in the development of
      effective therapeutic as well as preventive strategies against HIV/AIDS.

PMID- 22360745
TI  - Self-medication of regular headache: a community pharmacy-based survey.
AB  - BACKGROUND: This observational community pharmacy-based study aimed to
      investigate headache characteristics and medication use of persons with regular
      headache presenting for self-medication. METHODS: Participants (n = 1205)
      completed (i) a questionnaire to assess current headache medication and previous
      physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine
      Disability Assessment questionnaire. RESULTS: Forty-four percentage of the study
      population (n = 528) did not have a physician diagnosis of their headache, and
      225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly
      used acute headache drugs were paracetamol (used by 62% of the study population),
      NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician
      diagnosed with migraine used prophylactic migraine medication, and 25% used
      triptans. About 24% of our sample (n = 292) chronically overused acute
      medication, which was combination analgesic overuse (n = 166), simple analgesic
      overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid
      overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute
      headache treatments. CONCLUSIONS: This study identified underdiagnosis of
      migraine, low use of migraine prophylaxis and triptans, and high prevalence of
      medication overuse amongst subjects seeking self-medication for regular headache.
      Community pharmacists have a strategic position in education and referral of
      these self-medicating headache patients.

PMID- 22360746
TI  - Spectroscopic and photophysical properties of dUTP and internally DNA bound
      fluorophores for optimized signal detection in biological formats.
AB  - Efficient signal generation in DNA-based assays requires understanding of the
      influence of fluorophore's interactions on the spectroscopic properties. The
      resulting changes in fluorescence intensity, quantum yield, emission anisotropy,
      and fluorescence lifetime provide straightforward tools for the study of
      molecular dynamics and interaction between labels and nucleic acids. Searching
      for bright fluorescent reporters for rolling circle amplification (RCA) as
      efficient signal enhancement strategy for biological formats, we investigated the
      spectroscopic properties of seven dyes: cyanines, rhodamines, and BODIPYs. They
      spectrally resemble Cy3, the most frequently used fluorophore in biodetection
      formats, and are measured in six samples (free dye, dye-dUTP, internally labeled
      ssDNA and dsDNA-single- and triple-labeled) using steady-state and time-resolved
      fluorometry. Special emphasis was dedicated to characterizing the nature of the
      interaction of these fluorophores differing in dye class, charge, and rigidity.
      Our results suggest dye charge and structure as main factors governing the dye's
      interactions, with DY-555 and Cy3B presenting the best candidates for our
      envisaged signal amplification strategy. This label comparison underlines the
      importance of a proper understanding of structure-property relations and dye
      biomolecule interactions for reporter choice and presents a road map towards the
      design and interpretation of experiments using these labels on DNA of known
      sequence.

PMID- 22360748
TI  - Xenotransplantation: the near future.

PMID- 22360747
TI  - Beneficial effect of Bradycardia Tachycardia Response (BTR) algorithm on VT
      detection in the presence of rate smoothing.
AB  - INTRODUCTION: Rate smoothing algorithms, while known to help prevent ventricular
      tachyarrhythmias in some patients, have been shown to result in underdetection of
      ventricular tachycardia (VT) due to interaction between bradycardia pacing and
      tachycardia detection parameters. A new algorithm named Bradycardia Tachycardia
      Response (BTR) has been developed in order to prevent rate smoothing-induced
      underdetection. The efficacy of BTR is not known. The aim of this study was to
      assess the effectiveness of BTR in preventing VT underdetection due to rate
      smoothing. METHODS AND RESULTS: Two ICD models (TELIGEN and VITALITY AVT, Boston
      Scientific, St. Paul, MN, USA) bearing identical rate smoothing algorithms were
      connected to a VT simulator. Devices were programmed similarly except for the BTR
      feature that exists in TELIGEN only. The detection performance of both devices
      was tested using varying combinations of AV delay, rate smoothing down, and upper
      rate limit and compared between the two models. VT underdetection (delay or
      nondetection) occurred during pacing in 62% of the VT episodes with VITALITY AVT.
      In TELIGEN, all simulated VT episodes were detected appropriately as soon as
      their rates exceeded the programmed VT detection rate. Detection tended to be
      affected by higher upper rate, longer AV delays, and more aggressive rate
      smoothing. CONCLUSION: The BTR algorithm effectively counteracts VT detection
      delay caused by the interaction of rate smoothing with VT detection parameters,
      thus enabling safe use of the rate smoothing feature.

PMID- 22360751
TI  - Differences in human and porcine platelet oligosaccharides may influence
      phagocytosis by liver sinusoidal cells in vitro.
AB  - BACKGROUND: Acute thrombocytopenia was revealed as a limiting factor to porcine
      liver xenotransplantation from in vitro and in vivo studies using porcine liver
      in human and baboon transplant models. The asialoglycoprotein receptor 1 (ASGR1)
      on liver sinusoidal endothelial cells (LSEC) and macrophage antigen complex-1
      (Mac-1) on Kupffer cells (KC) mediate platelet phagocytosis and have carbohydrate
      binding sites that recognize galactose and N-acetyl glucosamine in the beta
      conformation. Analysis of these receptor carbohydrate-binding domains and surface
      carbohydrates on human and porcine platelets may shed light on the mechanism of
      xenotransplantation-induced thrombocytopenia. METHODS: An amino acid sequence
      comparison of human and porcine ASGR1 lectin-binding domains was performed. Using
      fluorescent labeled-lectins, human platelets, domestic and alpha1,3
      galactosyltransferase knockout/human decay accelerating factor, porcine platelets
      were characterized by flow cytometry and lectin blot analyses. After
      desialylation, human and porcine platelets were examined by flow cytometry to
      determine whether sialic acid capping of galactose and N-acetyl glucosamine
      oligosaccharides in the beta conformation was a factor. Further, desialylated
      human platelets were studied on primary porcine liver sinusoidal cells with
      regard to binding and phagocytosis. RESULTS: Human platelets have four times more
      exposed galactose beta1-4 N-acetyl glucosamine (Galbeta) and N-acetyl glucosamine
      beta1-4 N-acetyl glucosamine (betaGlcNAc) than fresh porcine platelets. Galbeta
      and betaGlcNAc moieties on porcine platelets were not masked by sialic acid.
      Removal of sialic acid from human platelets increased binding and phagocytosis by
      LSEC and KC. CONCLUSIONS: Differences between human and porcine ASGR1 and Mac-1,
      in combination with a significantly higher number of galactose and N-acetyl
      glucosamine-containing oligosaccharides on human platelets contribute, in part,
      to platelet loss seen in porcine liver xenotransplantation.

PMID- 22360750
TI  - T-cell-mediated immunological barriers to xenotransplantation.
AB  - Xenotransplantion remains the most viable option for significant expansion of the
      donor organ pool in clinical transplantation. With the advent of nuclear transfer
      technologies, the production of transgenic swine has become a possibility. These
      animals have allowed transplant investigators to overcome humoral mechanisms of
      hyperacute xenograft rejection in experimental pig-to-non-human primate models.
      However, other immunologic barriers preclude long-term acceptance of xenografts.
      This review article focuses on a major feature of xenogeneic rejection:
      xenogeneic T cell responses. Evidence obtained from both small and large animal
      models, particularly those using either islet cells or kidneys, have demonstrated
      that T cell responses play a major role in xenogeneic rejection, and that
      immunosuppression alone is likely incapable of completely suppressing these
      responses. Additionally, both the direct and indirect pathway of antigen
      presentation appear to be involved in these anti donor processes. Enhanced
      understanding of (i) CD47 and its role in transduced xeno-bone marrow (ii) CD39
      and its role in coagulation dysregulation and (iii) thymic transplantation have
      provided us with encouraging results. Presently, experiments evaluating the
      possibility of xenogeneic tolerance are underway.

PMID- 22360752
TI  - Human TNF-related apoptosis-inducing ligand-expressing dendritic cells from
      transgenic pigs attenuate human xenogeneic T cell responses.
AB  - BACKGROUND: Efficient and precise techniques for the genetic modification of pigs
      facilitate the generation of tailored donor animals for xenotransplantation.
      Numerous transgenic pig lines exist with the focus on inhibition of the
      complement system and of humoral immune responses. In addition, immune cell-based
      responses need to be controlled to prevent pig-to-primate xenograft rejection.
      Expression of human (hu) TNF-related apoptosis-inducing ligand (TRAIL) on porcine
      cells has the potential to ameliorate human T cell responses. METHODS: We
      generated transgenic pigs expressing human tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (huTRAIL) under the control of either the mouse H2K(b)
      promoter or a CMV enhancer/chicken beta-actin (CAG) promoter, the latter one (CAG
      huTRAIL) on a GGTA1 knockout/huCD46 transgenic background. The biological
      activity of huTRAIL was demonstrated by its apoptosis-inducing effect on Jurkat
      lymphoma cells. To clarify whether huTRAIL affects also primary immune cells and
      whether its effects depend on the presence of co-stimulatory molecules, we
      exposed human peripheral blood mononuclear cells (PBMC) or isolated T cells to
      huTRAIL-expressing porcine fibroblasts or dendritic cells in vitro. RESULTS: H2Kb
      huTRAIL transgenic pigs express huTRAIL mainly in the spleen and secondary
      lymphoid tissues. The CAG-huTRAIL construct facilitated huTRAIL expression in
      multiple organs, the level being at least one order of magnitude higher than in
      H2Kb-huTRAIL transgenic pigs. Incubation with huTRAIL-expressing H2Kb-huTRAIL
      transgenic porcine dendritic cells decreased human T cell proliferation
      significantly without any signs of apoptosis. In spite of the high transgene
      expression level, CAG-huTRAIL transgenic fibroblasts did not affect proliferation
      of human PBMC, independent of their activation state. CONCLUSIONS: These results
      suggest huTRAIL expression on porcine dendritic cells as a possible strategy to
      attenuate T cell responses against pig-to-primate xenografts.

PMID- 22360753
TI  - Porcine alanine transaminase after liver allo-and xenotransplantation.
AB  - Aspartate transaminase (AST) and alanine transaminase (ALT) are measured
      following liver transplantation as indicators of hepatocellular injury. During a
      series of orthotopic liver allo-and xenotransplants, we observed that there was
      an increase in AST in all cases. The anticipated concomitant rise in ALT did not
      occur when a wild-type (WT) pig was the source of the liver graft, but did occur
      when a baboon or a genetically engineered (alpha1,3-galactosyltransferase gene
      knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience
      of Galalpha1,3Gal in GTKO pig livers may render pig hepatocytes similar to human
      and baboon hepatocytes in their response to hepatocellular injury. Reviewing the
      literature, after WT pig liver allotransplantation or xenotransplantation, in the
      majority of reports, although changes in AST were reported, no mention was made
      of changes in ALT, suggesting that there was no change in ALT. However, Ramirez
      et al. reported two cases of liver xenotransplants from hCD55 pigs, following
      which there were increases in both AST and ALT, suggesting that it is not simply
      the cience of expression of Galalpha1,3Gal that is the cause. We acknowledge that
      our observation is based on a small number of experiments, but we believe it is
      worth recording.

PMID- 22360756
TI  - Xenotransplantation literature update, November-December 2011.

PMID- 22360757
TI  - [M(rac-N-benzyl Asp)(H2O)] (M = Co, Ni): noncentrosymmetric coordination
      polymeric chains with racemic chiral ligands.
AB  - The hydrothermal reaction of fumaric acid, benzylamine, and metal salts yielded
      M[(rac-N-benzyl-Asp)(H(2)O)] (M = Co, Ni), 1 and 2, and Ni[(rac-N-benzyl
      Asp)(H(2)O)(3)].H(2)O 3. Under mild hydrothermal conditions, Michael addition of
      benzylamine to fumaric acid led to the formation of a racemic mixture of N-benzyl
      aspartic acid enantiomers. The noncentrosymmetric structures of 1 and 2 consist
      of one-dimensional polymeric chains in which metal cations are bridged by d- and
      l-N-benzyl aspartate anions alternating along the chain. The centrosymmetric
      structure of 3 is composed of discrete Ni[(rac-N-benzyl-Asp)(H(2)O)(3)] units
      that are connected by hydrogen bonds into layers. The single layers are
      homochiral but are hydrogen bonded to similar homochiral layers that contain the
      N-benzyl aspartate with the opposite handedness. Compounds 1 and 2 showed second
      harmonic generation (SHG), and their magnetic and thermodynamic properties are
      described.

PMID- 22360754
TI  - The effect of Gal expression on pig cells on the human T-cell xenoresponse.
AB  - BACKGROUND:   Lack of Gal expression on pig cells is associated with a reduced
      primate humoral immune response as well as a reduction in cytokine production by
      human cells in vitro. We investigated whether lack of Gal expression is
      associated with reduced human T-cell response in vitro. METHODS:   Peripheral
      blood mononuclear cells (PBMCs) were obtained from healthy humans and naive
      baboons. Human CD4+ and CD8+ T cells were isolated. Porcine aortic endothelial
      cells (pAECs) were isolated from wild-type (WT) and alpha1,3
      galactosyltransferase gene-knockout (GTKO) pigs. WT pAECs were treated with alpha
      galactosidase, reducing Gal expression. Swine leukocyte antigen (SLA) class I and
      II expression on pAECs was measured, as was T-cell proliferation and cytokine
      production in response to pAECs. RESULTS: Reduced Gal expression on WT pAECs
      after alpha-galactosidase treatment was associated with reduced human PBMC
      proliferation (P<0.005). SLA class I and II expression on WT and GTKO pAECs was
      comparable. Human CD4+ and CD8+ T-cell proliferation was less against GTKO pAECs
      before (P<0.001) and after (P<0.01 and P<0.05, respectively) activation. Human
      and baboon PBMC proliferation was less against GTKO pAECs before (P<0.05) and
      after (P<0.01 and P<0.05, respectively) activation. Human PBMCs produced a
      comparable cytokine/chemokine response to WT and GTKO pAECs. However, there was
      less production of IFN-gamma/TNF-alpha by CD4+ and IFN-gamma/granzyme B/IP-10 by
      CD8+ T cells in response to GTKO pAECs. CONCLUSIONS:   The absence of Gal on pig
      cells is associated with reduced human T-cell proliferation (and possibly
      selected cytokine production). Adaptive primate T-cell responses are likely to be
      reduced in GTKO xenograft recipients.

PMID- 22360759
TI  - Widespread cortical morphologic changes in juvenile myoclonic epilepsy: evidence
      from structural MRI.
AB  - PURPOSE: Atypical morphology of the surface of the cerebral cortex may be related
      to abnormal cortical folding (gyrification) and therefore may indicate underlying
      malformations of cortical development (MCDs). Using magnetic resonance imaging
      (MRI)-based analysis, we examined cortical morphology in patients with juvenile
      myoclonic epilepsy (JME). METHODS: MRI data was collected for 24 patients with
      JME and 40 demographically matched healthy controls. FreeSurfer, an automated
      cortical surface reconstruction method, was applied to compare cortical
      morphology between patients and controls. Areas of anomalous cortical morphology
      were defined as regions of interest (ROIs) to contrast regional cortical
      parameters, such as surface area, average thickness, and mean curvature between
      patients and controls. KEY FINDINGS: In patients with JME, changes to cortical
      morphology were detected in several regions. In the left hemisphere, these were
      in insular and cingulate cortices, occipital pole, and middle temporal and
      fusiform gyri. In the right hemisphere, changes were detected in insular cortex,
      inferior temporal gyrus, and precuneus. Further analysis of ROIs revealed that
      these changes are related to differences in surface area rather than average
      cortical thickness. In addition, mean curvature abnormalities were detected in
      the insula bilaterally, the left cingulate cortex, and right inferior temporal
      gyrus. SIGNIFICANCE: The morphologic findings in this study suggest that
      structural abnormalities in JME extend beyond mesial frontal lobe regions of the
      brain. These may be indicative of areas of subtle cortical folding abnormality
      related to early disruption of cortical development.

PMID- 22360758
TI  - The enolization chemistry of a thioester-dependent racemase: the 1.4 A crystal
      structure of a reaction intermediate complex characterized by detailed QM/MM
      calculations.
AB  - In the active site of the bacterial alpha-methylacyl-CoA racemase of 
      Mycobacterium tuberculosis  (MCR), the chirality of the 2-methyl branched C2-atom
      is interconverted between (S) and (R) isomers. Protein crystallographic data and
      quantum mechanics/molecular mechanics (QM/MM) computational approaches show that
      this interconversion is achieved via a planar enolate intermediate. The crystal
      structure, at 1.4 A, visualizes the mode of binding of a reaction intermediate
      analogue, 2-methylacetoacetyl-CoA, in a well-defined planar enolate form. The
      computational studies confirm that in the conversion from (S) to (R), first a
      proton is abstracted by Ndelta1 (His126), and subsequently the planar enolate
      form is reprotonated by Odelta2 (Asp156). The calculations also show that the
      negatively charged thioester oxygen of the enolate intermediate is stabilized by
      an oxyanion hole formed by N (Asp127), as well as by the side chain atoms of the
      catalytic residues, Asp156 and His126, both being protonated simultaneously, at
      the intermediate stage of the catalytic cycle. The computational analysis also
      reveals that the conversion of the (S)- to (R)- chirality is achieved by a
      movement of 1.7 A of the chiral C2-carbon, with smaller shifts (approximately 1
      A) of the carbon atom of the 2-methyl group, the C3-atom of the fatty acid tail,
      and the C1-carbon and O1-oxygen atoms of the thioester moiety.

PMID- 22360760
TI  - Fluorescent in situ hybridization with arbitrarily amplified DNA fragments
      differentiates carrot (Daucus carota L.) chromosomes.
AB  - Carrot (Daucus carota L.) chromosomes are small and poorly differentiated in size
      and morphology. Here we demonstrate that fluorescent in situ hybridization (FISH)
      signals derived from arbitrary PCR probes can be used for chromosome
      identification in carrot. To prepare probes, we searched for nonpolymorphic
      products abundantly amplified with arbitrary decamer primers in a group of
      accessions representing carrot genetic diversity. As a result, 13 fragments
      ranging in size from 517 to 1758 bp were selected, sequenced, and used as probes
      for fluorescent in situ hybridization. Four of these probes produced clear and
      reproducible hybridization signals. The sequences showed similarity to a number
      of carrot BAC-end sequences, indicating their repetitive character. Three of them
      were similar to internal portions of gypsy and copia LTR retrotransposons
      previously identified in plants. Hybridization signals for the four probes were
      observed as dotted tracks on chromosomes, differing in distribution and
      intensity. Generally, they were present in pericentromeric and (or) interstitial
      localizations on chromosome arms. The use of the four probes allowed
      discrimination of chromosome pairs and construction of more detailed karyotypes
      and idiograms of carrot.

PMID- 22360761
TI  - Remembering the past and imagining the future: examining the consequences of
      mental time travel on memory.
AB  - Cognitive, neuropsychological, and neuroimaging evidence suggests that
      remembering the past and imagining the future rely on overlapping processes in
      episodic memory. The three experiments reported here examine the consequences of
      remembering the past and imagining the future on the accessibility of other
      information in memory. Participants first studied events associated with a
      specific context and then either (a) retrieved past autobiographical events
      associated with that same context or (b) imagined future autobiographical events
      associated with that same context. Replicating and extending evidence of
      retrieval-induced forgetting, remembering autobiographical events from the past
      caused participants to forget the related studied events. However, imagining
      future autobiographical events failed to cause participants to forget the related
      studied events. These results suggest an important difference in the memorial
      consequences of remembering and imagining.

PMID- 22360762
TI  - Reflections on giving bad news.
AB  - Death in the emergency department (ED) is fairly common. Giving bad news can be
      difficult, but it is a skill that is vitally important for the emergency
      physician. In the past it may have been difficult to find good resources on the
      subject, but now there are many reviews and guidelines; the SPIKES and GRIEV_ING
      protocols are two such guidelines. Furthermore, giving bad news is now taught in
      medical school and residency. This reflection is about giving the news of the
      death of a family member over the telephone. Little literature addresses giving
      bad news over the telephone.

PMID- 22360763
TI  - Assessment of consecutive neurolytic celiac plexus block (NCPB) technique
      outcomes in the management of refractory visceral cancer pain.
AB  - OBJECTIVE: The objective of this study was to assess outcomes and safety of
      consecutive neurolytic celiac plexus block (NCPB) technique. DESIGN:
      Retrospective clinical data analysis. SETTING: The study was conducted in three
      pain departments and academic medical center. PATIENTS: The subject of this study
      was 12 patients with terminal visceral (mostly pancreatic) cancer who failed
      conservative measures. INTERVENTIONS: Twelve celiac plexus alcohol neurolytic
      procedures were performed for pain control after a positive diagnostic block.
      MATERIALS AND METHODS: Twelve patients with terminal visceral (mostly pancreatic)
      cancer who failed conservative measures were managed by consecutive NCPB guided
      by computed tomography at the pain department of Beijing Xuanwu Hospital between
      January 2005 and June 2010. The present study evaluated the efficacy of
      consecutive NCPB technique with regard to pain relief, as well as its adverse
      effects and complications. RESULTS: The efficacy of consecutive NCPB technique
      with regard to pain relief was observed by a marked decrease in the visual analog
      score and in opioid consumption, with preprocedural mean values dropping from
      (8.7+/-1.0) and (155+/-56)mg/day of morphine to (1.8+/-1.1) and (0)mg/day at the
      first postprocedural visit, respectively. These results persisted during the 6
      month follow-up period or until death. Minor adverse effects (moderate diarrhea
      and mild hypotension) were frequent (N=3, and N=4, respectively), and severe
      complications occurred in one patient with a transient paraparesis (N=1). No
      procedure-related mortality was observed. CONCLUSIONS: The consecutive NCPB
      technique can provide analgesia and the alleviation of the secondary undesirable
      effects of analgesic drugs resulting from the decrease of morphine consumption in
      patients with upper abdominal malignancies. In the subject group, the reliability
      of its analgesic effect is high, with lower rate of severe complications.

PMID- 22360764
TI  - Canine eyelid granular cell tumor: a report of eight cases.
AB  - To describe a previously unreported neoplasm of the medial canthus and eyelid in
      dogs. Clinical and pathologic features of granular cell tumors in the dog were
      reviewed. Granular cell tumors, arising from the medial canthal eyelid of eight
      dogs, were identified from the archives of the Comparative Ocular Pathology
      Laboratory of Wisconsin (COPLOW). The affected dogs ranged in age from 5 to 12
      years (mean of 9.25 years). Follow-up information was available for seven of the
      eight cases. The clinical presentation included swollen hyperemic lids (4/8),
      ulcerated skin overlying the mass (2/8), and red conjunctiva (7/8). All eight of
      the cases had firm masses extending from the palpebral conjunctiva to the eyelid
      margin at the medial canthus. Histologically, the tissue was composed of a highly
      collagenous neoplastic growth. The neoplastic cells were oval to strap-like cells
      with an oval bland appearing nucleus and abundant amounts of granular cytoplasm
      with very distinct cell boundaries. These granular cells were embedded in a dense
      collagen matrix. A PAS stain faintly highlighted the granular appearance of the
      neoplastic cells, which is a defining characteristic of this tumor. There was no
      recurrence in the seven cases available for follow-up. Canine granular cell
      tumors of the medial canthus present clinically and histologically as a benign
      neoplasm. Granular cell tumors have a characteristic histological appearance.
      Granular cell tumors should be on the differential list for nodules of the medial
      canthus in dogs.

PMID- 22360765
TI  - The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301
      loaded PLGA microsphere) on short-term memory impairment in rats with transient
      global cerebral ischemia.
AB  - The purpose of this study was to prepare the ONO-1301 loaded poly(lactide-co
      glycolide) microsphere (ONO-1301 PLGA MS) and to evaluate neuroprotective effects
      for short-term memory by a single subcutaneous injection of ONO-1301 PLGA MS on
      repeated induction of cerebral ischemia (2 * 10-min with a 1-min interval) in
      rat. Drug release profiles from ONO-1301 PLGA MS in vitro and in vivo were
      evaluated. The extent of ischemic injury was assessed behaviourally using the
      passive avoidance test and histopathologically by evaluating hippocampal CA1
      pyramidal damage on day 42 after ischemia. Experiments in vitro showed that the
      release of ONO-1301 from ONO-1301 PLGA MS was sustained for approximately 3 weeks
      with maintenance of steady plasma levels. The neuroprotective effect was shown by
      treatment with ONO-1301 PLGA MS from 2 days after induction of ischemia
      behaviourally and histopathologically. These results suggest that ONO-1301 PLGA
      MS can limit short-term learning injury following global cerebral ischemia.

PMID- 22360767
TI  - Infrared photodissociation spectroscopy of mononuclear iron carbonyl anions.
AB  - The infrared photodissociation spectroscopy of mass-selected mononuclear iron
      carbonyl anions Fe(CO)(n)(-) (n = 2-8) were studied in the carbonyl stretching
      frequency region. The FeCO(-) anion does not fragment when excited with infrared
      light. Only a single IR active band was observed for the Fe(CO)(2)(-) and
      Fe(CO)(3)(-) anions, consistent with theoretical predictions that these complexes
      have linear D(infinityh) and planar D(3h) symmetry, respectively. The Fe(CO)(4)(
      ) anion is the most intense peak in the mass spectra and was characterized to
      have a completed coordination sphere with high stability. Anion clusters larger
      than n = 4 were determined to involve a Fe(CO)(4)(-) core anion that is
      progressively solvated by external CO molecules. Three CO stretching vibrational
      fundamentals were observed for the Fe(CO)(4)(-) core anion, indicating that the
      Fe(CO)(4)(-) anion has a C(3v) structure. All the carbonyl stretching frequencies
      of the Fe(CO)(n)(-) anion complexes are red-shifted with respect to those of the
      corresponding neutrals.

PMID- 22360766
TI  - Noninvasive assessment of liver fibrosis in adult patients following the Fontan
      procedure.
AB  - OBJECTIVE:   Recent data indicate that patients after the Fontan procedure are at
      risk for significant liver dysfunction; however, the prevalence and extent of
      liver disease in the Fontan population remains unknown. Furthermore, limited data
      exist in regard to screening for liver disease in adult Fontan patients. We
      sought to determine the prevalence of liver disease in adult patients following
      the Fontan procedure using computed tomography (CT) and serum biomarkers of liver
      fibrosis. DESIGN:   Adult Fontan patients underwent screening for liver disease
      as part of their annual evaluation. Screening consisted of laboratory evaluation
      and dual-phase liver CT scan. Laboratory evaluation included analysis of liver
      function, viral hepatitis serologies, and FibroSURE panel (LabCorp), a test that
      analyzes the results of serum biomarkers to provide a quantitative surrogate
      marker for liver fibrosis. RESULTS:   Sixteen patients, mean age 30.3 (range 20
      41) years, were enrolled in the study. Mean length of follow-up from time of
      Fontan palliation was 20.5 (range 11-33) years. No patients had serologic
      evidence of viral hepatitis or synthetic liver dysfunction. Twelve patients (75%)
      had abnormal FibroSURE scores, seven (44%) had elevated FibroSURE scores
      predictive of Metavir fibrosis stage F2 or greater on liver biopsy, and one (6%)
      had a FibroSURE score predictive of cirrhosis on biopsy. All 16 patients had
      abnormal radiologic liver findings identified on CT, including heterogeneous
      enhancement in 11 (69%), varices in six (38%), and liver nodules in five patients
      (31%). Length of time since Fontan surgery correlated significantly with an
      elevated FibroSURE score (P = .05) and having more CT scan abnormalities (P =
      .04). CONCLUSIONS:   Liver fibrosis detected by serum biomarkers and dual phase
      CT scan is common in adult patients following the Fontan procedure. Further
      studies are needed to determine the long-term clinical significance of these
      findings.

PMID- 22360768
TI  - Synthesis of functionalized dioxa-aza[7]helicenes using palladium catalyzed
      arylations.
AB  - Despite the recent reports on transition-metal catalyzed cycloisomerization
      strategies toward helicenes, the amount of palladium catalyzed routes remains
      rather scarce. Within this letter the successful preparation and characterization
      of novel dioxa-aza[7]helicenes using palladium mediated coupling reactions is
      presented.

PMID- 22360769
TI  - Comparison of random forest and Pipeline Pilot Naive Bayes in prospective QSAR
      predictions.
AB  - Random forest is currently considered one of the best QSAR methods available in
      terms of accuracy of prediction. However, it is computationally intensive. Naive
      Bayes is a simple, robust classification method. The Laplacian-modified Naive
      Bayes implementation is the preferred QSAR method in the widely used commercial
      chemoinformatics platform Pipeline Pilot. We made a comparison of the ability of
      Pipeline Pilot Naive Bayes (PLPNB) and random forest to make accurate predictions
      on 18 large, diverse in-house QSAR data sets. These include on-target and ADME
      related activities. These data sets were set up as classification problems with
      either binary or multicategory activities. We used a time-split method of
      dividing training and test sets, as we feel this is a realistic way of simulating
      prospective prediction. PLPNB is computationally efficient. However, random
      forest predictions are at least as good and in many cases significantly better
      than those of PLPNB on our data sets. PLPNB performs better with ECFP4 and ECFP6
      descriptors, which are native to Pipeline Pilot, and more poorly with other
      descriptors we tried.

PMID- 22360771
TI  - Enhanced flagging and improved clinical sensitivity on the new DxH 300(TM)
      Coulter((r)) cellular analysis system.
AB  - INTRODUCTION:  The Beckman Coulter DxH 300TM is a hematology analyzer that
      performs a CBC and 3-part WBC differential and incorporates new electronic,
      algorithm and mechanical design. METHODS:  This instrument was compared with the
      predicate analyzer (Coulter((r)) A(c) .Tdiff2) and the larger format Coulter
      LH780 analyzer. Of interest were flagging rates, clinical sensitivity, and
      accuracy of the WBC in the presence of interfering particles. The total sample
      set (n = 404) consisted of morphologically normal and hematologically abnormal
      patients. RESULTS: Correlation of the DxH 300 with A(c) .Tdiff2TM showed good
      agreement with all directly measured parameters. When compared with the LH780,
      WBC and platelets (PLT) counts showed good agreement with small biases.
      Importantly in the low range (PLT <50 * 10(9) /L), there was a small positive
      bias of only 2 * 10(9) /L PLT. Interfering particles did not affect the DxH 300
      WBC count (P > 0.05) with strong correlations to the LH780 (r(2) values >0.95).
      Importantly, overall and specific flagging rates as well as false-negative and
      false-positive rates were significantly reduced on the DxH 300 compared with the
      A(c) .Tdiff2 (27% and 41% reduction, respectively, P < 0.001). CONCLUSIONS:  The
      DxH 300 offers significant improvement over the predicate Coulter analyzer in
      flagging rates and improved correlation with larger format analyzers for WBC and
      PLT counts. Reduced false negatives and false positives significantly improved
      sensitivity and specificity compared to the predicate analyzer. The 28%
      improvement in flagging efficiency together with numerous software and data
      handling enhancements should translate into reduced need to perform follow-up
      analysis on a significant number of samples.

PMID- 22360770
TI  - Improving access to health care for malaria in Africa: a review of literature on
      what attracts patients.
AB  - BACKGROUND: Increasing access to health care services is considered central to
      improving the health of populations. Existing reviews to understand factors
      affecting access to health care have focused on attributes of patients and their
      communities that act as 'barriers' to access, such as education level, financial
      and cultural factors. This review addresses the need to learn about provider
      characteristics that encourage patients to attend their health services. METHODS:
      This literature review aims to describe research that has identified
      characteristics that clients are looking for in the providers they approach for
      their health care needs, specifically for malaria in Africa. Keywords of
      'malaria' and 'treatment seek*' or 'health seek*' and 'Africa' were searched for
      in the following databases: Web of Science, IBSS and Medline. Reviews of each
      paper were undertaken by two members of the team. Factors attracting patients
      according to each paper were listed and the strength of evidence was assessed by
      evaluating the methods used and the richness of descriptions of findings.
      RESULTS: A total of 97 papers fulfilled the inclusion criteria and were included
      in the review. The review of these papers identified several characteristics that
      were reported to attract patients to providers of all types, including lower cost
      of services, close proximity to patients, positive manner of providers, medicines
      that patients believe will cure them, and timeliness of services. Additional
      categories of factors were noted to attract patients to either higher or lower
      level providers. The strength of evidence reviewed varied, with limitations
      observed in the use of methods utilizing pre-defined questions and the uncritical
      use of concepts such as 'quality', 'costs' and 'access'. Although most papers
      (90%) were published since the year 2000, most categories of attributes had been
      described in earlier papers. CONCLUSION: This paper argues that improving access
      to services requires attention to factors that will attract patients, and
      recommends that public services are improved in the specific aspects identified
      in this review. It also argues that research into access should expand its lens
      to consider provider characteristics more broadly, especially using methods that
      enable open responses. Access must be reconceptualized beyond the notion of
      barriers to consider attributes of attraction if patients are to receive quality
      care quickly.

PMID- 22360772
TI  - Galvanic vestibular stimulation improves the results of vestibular
      rehabilitation.
AB  - Here, we present findings from a three-step investigation of the effect of
      galvanic vestibular stimulation (GVS) in normal subjects and in subjects
      undergoing vestibular rehabilitation (VR). In an initial study, we examined the
      body sway of 10 normal subjects after one minute of 2 mA GVS. The effect of the
      stimulation lasted for at least 20 minutes in all subjects and up to two hours in
      70% of the subjects. We then compared a group of patients who received
      conventional VR (40 patients) with a group that received a combination of VR and
      GVS. Results suggest a significant improvement in the second group. Finally, we
      attempted to establish the optimal number of GVS sessions and to rule out a
      placebo effect. Fifteen patients received "systematic" GVS: five sessions, once a
      week. Five patients received "nonsystematic" galvanic stimulation in a sham
      protocol, which included two stimulations of the clavicle. These data were
      analyzed with Fisher's exact test and indicated that the best results were
      obtained after three sessions of GVS and no placebo effect was observed.

PMID- 22360773
TI  - Highly luminescent half-lantern cyclometalated platinum(II) complex: synthesis,
      structure, luminescence studies, and reactivity.
AB  - The half-lantern compound [{Pt(bzq)(MU-C(7)H(4)NS(2)-kappaN,S)}(2)].Me(2)CO (1)
      was obtained by reaction of equimolar amounts of potassium 2
      mercaptobenzothiazolate (KC(7)H(4)NS(2)) and [Pt(bzq)(NCMe)(2)]ClO(4). The
      Pt(II)...Pt(II) separation in the neutral complex [{Pt(bzq)(MU-C(7)H(4)NS(2)
      kappaN,S)}(2)] is 2.910 (2) A, this being among the shortest observed in half
      lantern divalent platinum complexes. Within the complex, the benzo[h]quinoline
      (bzq) groups lie in close proximity with most C...C distances being between 3.3
      and 3.7 A, which is indicative of significant pi-pi interactions. The reaction of
      1 with halogens X(2) (X(2) = Cl(2), Br(2), or I(2)) proceeds with a two-electron
      oxidation to give the corresponding dihalodiplatinum(III) complexes [{Pt(bzq)(MU
      C(7)H(4)NS(2)-kappaN,S)X}(2)] (X = Cl 2, Br 3, I 4). Their X-ray structures
      confirm the retention of the half-lantern structure and the coordination mode of
      the bzq and the bridging ligand MU-C(7)H(4)NS(2)-kappaN,S. The Pt-Pt distances
      (Pt-Pt = 2.6420(3) A 2, 2.6435(4) A 3, 2.6690(3) A 4) are shorter than that in 1
      because of the Pt-Pt bond formation. Time dependent-density functional theory (TD
      DFT) studies performed on 1 show a formal bond order of 0 between the metal
      atoms, with the 6p(z) contribution diminishing the antibonding character of the
      highest occupied molecular orbital (HOMO) and being responsible for an attractive
      intermetallic interaction. A shortening of the Pt-Pt distance from 2.959 A in the
      ground state S(0) to 2.760 A in the optimized first excited state (T(1)) is
      consistent with an increase in the Pt-Pt bond order to 0.5. In agreement with TD
      DFT calculations, the intense, structureless, red emission of 1 in the solid
      state and in solution can be mainly attributed to triplet metal-metal-to-ligand
      charge transfer ((3)MMLCT) [dsigma*(Pt-Pt) -> pi*(bzq)] excited states. The high
      quantum yields of this emission measured in toluene (44%) and solid state (62%)
      at room temperature indicate that 1 is a very efficient and stable (3)MMLCT
      emitter, even in solution. The high luminescence quantum yield of its red
      emission, added to its neutral character and the thermal stability of 1, make it
      a potential compound to be incorporated as phosphorescent dopant in multilayer
      organic light-emitting devices (OLEDs).

PMID- 22360774
TI  - Pharmacovigilance.
AB  - Adverse drug reactions are the fifth most frequent cause of deaths in developed
      countries, effectively a global epidemic. However, progress in ameliorating the
      problem has been slow. Pharmacovigilance currently operates without clear
      objectives in relation to individual decisions, with no protocol (although risk
      management plans are a great step forward), with obscure materials and methods
      used for making decisions, with very limited reasoning and discussion, and little
      or no follow up and audit of the results. Problems include under-reporting, poor
      quality reports, underuse of the latest communications technology and suboptimal
      individual feedback to reporters. Assessment of causality is poor, impeding
      decision-making. After signal detection, more active measures to assess the risk
      to public health are needed. Other essential factors include precision about the
      ways in which data are prepared and transformed into databases, the recognition
      of secondary effects, which may be more obvious than the primary effect, but not
      so easy to link causally, and cognisance of all kinds of interactions. Areas that
      should be developed include pharmacoepidemiology, knowledge finding (through data
      mining), and communication and systems technology. The general way forward seems
      clear: a rigorous way of documenting all the steps, from getting reports of harms
      into regulatory databases to assessing their effects on public health, is
      essential and should be publicly reviewed for weaknesses. In turn, matters would
      be much improved by input on benefit/harm perceptions from patient groups,
      influencing decisions about what should be the true targets for regulatory and
      pharmacovigilance activities, avoiding second guessing by regulators.

PMID- 22360775
TI  - The impact of silent vascular brain burden in cognitive impairment in Parkinson's
      disease.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) detected by magnetic
      resonance imaging (MRI) of the brain are associated with dementia and cognitive
      impairment in the general population and in Alzheimer's disease. Their effect in
      cognitive decline and dementia associated with Parkinson's disease (PD) is still
      unclear. METHODS: We studied the relationship between WMHs and cognitive state in
      111 patients with PD classified as cognitively normal (n = 39), with a mild
      cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional
      and follow-up study. Cognitive state was evaluated with a comprehensive
      neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted
      MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No
      differences in WMHs were found between the three groups in the cross-sectional
      study. A negative correlation was observed between semantic fluency and the
      subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re
      evaluated after a mean follow-up of 30 months, three patients converted into MCI
      and 5 into dementia. Progression of periventricular WMHs was associated with an
      increased conversion to dementia. A marginal association between the increase in
      total WMHs burden and worsening in the Mini Mental State Examination was
      encountered. CONCLUSIONS: White matter hyperintensities do not influence the
      cognitive status of patients with PD. Frontal WMHs have a negative impact on
      semantic fluency. Brain vascular burden may have an effect on cognitive
      impairment in patients with PD as WMHs increase overtime might increase the risk
      of conversion to dementia. This finding needs further confirmation in larger
      prospective studies.

PMID- 22360776
TI  - Proteogenic amino acids: chiral and racemic crystal packings and stabilities.
AB  - Crystal structures of chiral and racemic proteogenic amino acids are compared,
      over a database of 40 crystal structures and 20 chiral-racemic pairs. Wallach's
      rule does not apply. Solubility data show that the racemates tend to be slightly
      more stable than their chiral counterparts. Lattice energies are calculated by
      semiempirical PIXEL methods and by several ab initio methods, which also yield
      molecular energies. Results, especially molecular energies, are sensitive to
      small structural differences and therefore depend on the crystal structure
      accuracy. Surface effects in crystals of zwitterionic molecules require special
      attention. Energy differences between chiral and racemic crystals are typically
      around 10 kJ mol(-1), roughly the limit of our calculations. These suggest,
      however, that crystal stability tends to increase with decreasing crystal
      density, a result possibly related to the strong directionality of hydrogen
      bonds. The analysis of interaction energies between molecules related by specific
      symmetry operations shows that stabilization in homochiral crystal structures
      comes mainly from formation of screw-symmetric ribbons, whereas racemic crystal
      structures preferentially exhibit strongly stabilizing centrosymmetric dimers.

PMID- 22360777
TI  - DNA damage products (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines as potential
      biomarkers in human urine for atherosclerosis.
AB  - We hypothesized that DNA damage products (5'R)-8,5'-cyclo-2'-deoxyadenosine (R
      cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) may be well-suited biomarkers
      of risk and diagnosis for atherosclerosis. We tested this hypothesis by measuring
      the levels of R-cdA and S-cdA and another product, 8-hydroxy-2'-deoxyguanosine (8
      OH-dG), in urine of atherosclerosis patients and healthy individuals using liquid
      chromatography-tandem mass spectrometry with isotope dilution. We showed the
      presence of these products at significantly greater concentrations in urine of
      atherosclerosis patients than in that of healthy individuals. Our data suggest
      that R-cdA and S-cdA can be accurately and reproducibly measured in human urine
      as potential biomarkers of risk and diagnosis for atherosclerosis.

PMID- 22360778
TI  - Paratesticular extrarenal Wilms' tumor.

PMID- 22360779
TI  - Interaction of angiogenically stimulated intermediate CD163+
      monocytes/macrophages with soft hydrophobic poly(n-butyl acrylate) networks with
      elastic moduli matched to that of human arteries.
AB  - The cell population of peripheral blood monocytes/macrophages (MO) is
      heterogeneous: The majority of the MO are CD14++ CD16- and named "classical" (=
      MO1). Furthermore, two other subpopulations were described: CD14++ CD16+
      ("intermediate" = MO2) and CD14+ CD16++ ("non-classical" = MO3). It is reported
      that MO2 possess anti-inflammatory properties and express the MO lineage marker
      CD163. On a hydrophilic neutrally charged acrylamide-based hydrogel human
      intermediate (CD14++ CD16+ ), angiogenically stimulated CD163++
      monocytes/macrophages (aMO2) maintained a proangiogenic and noninflammatory
      status for at least 14 days. Here, we explored whether this aMO2 subset adhered
      to hydrophobic poly(n-butyl acrylate) networks (cPnBA) and also remained in its
      proangiogenic and noninflammatory status. Because substrate elasticity can impact
      adherence, morphology, and function of cells, cPnBAs with different Young's
      modulus (250 and 1100 kPa) were investigated, whereby their elasticity was
      tailored by variation of the cross-linker content and matched to the elasticity
      of human arteries. The cPnBAs exhibited similar surface properties (e.g., surface
      roughness), which were maintained after ethylene oxide sterilization and exposure
      in serum-free cell culture medium for 18 h at 37 degrees C. aMO2 were seeded on
      cPnBA samples (1.7 * 10(5) cells/1.33 cm(2) ) in Dulbecco's modified Eagle medium
      (DMEM high glucose) supplemented with vascular endothelial growth factor 165
      (VEGF-A(165) , 10 ng/mL) and fetal calf serum (10 vol%) for 3 and 72 h. On both
      polymeric samples (n = 3 each), the numbers of adherent cells per unit area were
      significantly higher (P < 0.01; cPnBA0250: 3 h 13 +/- 5 cells/mm(2) , 72 h 234 +/
      106 cells/mm(2) ; cPnBA1100: 3 h 14 +/- 3 cells/mm(2) , 72 h 198 +/- 113
      cells/mm(2) ) compared to control cultures (glass, 3 h: 6 +/- 3 cells/mm(2) , 72
      h: 130 +/- 83 cells/mm(2) ) and showed a typically spread morphology. The mRNA
      expression profile of the aMO2 was not influenced by the substrate elasticity. In
      the supernatant of aMO2 on cPnBA0250, significantly less VEGF-A(165) product was
      found than expected based on the mRNA level measured (P < 0.01). Tests with
      recombinant VEGF-A(165) then demonstrated that significantly more VEGF-A(165) was
      adhered on cPnBA0250 than on cPnBA1100 (P < 0.01). Seeded on cPnBA, aMO2
      unaffected by the elastic moduli of both substrates-seemed to remain in their
      subset status and secreted VEGF-A(165) without release of proinflammatory
      cytokines. These in vitro results might indicate that this MO subset can be used
      as cellular delivery system for proangiogenic and noninflammatory mediators to
      support the endothelialization of cPnBA.

PMID- 22360780
TI  - The first mitochondrial genome for the wasp superfamily Platygastroidea: the egg
      parasitoid Trissolcus basalis.
AB  - The nearly complete mitochondrial (mt) genome of an egg parasitoid, Trissolcus
      basalis (Wollaston), was sequenced using both 454 and Illumina next-generation
      sequencing technologies. A portion of the noncoding region remained unsequenced,
      possibly owing to the presence of repeats. The sequenced portion of the genome is
      15,768 bp and has a high A+T content (84.2%), as is typical for hymenopteran mt
      genomes. A total of 36 of the 37 genes normally present in animal mt genomes were
      located. The one exception was trnR; a truncated version of this gene is present
      between trnS(1) and nd5, but it is unclear whether this gene fragment could code
      for the entire trnR gene. The mt gene arrangement of T. basalis is different from
      other Proctotrupomorpha mt genomes, with a number of trn genes in different
      positions. However, no shared derived gene rearrangements were identified in the
      present study. Bayesian analyses of mt genomes from 29 hymenopteran taxa and
      seven other orders of holometabolous insects support some uncontroversial
      evolutionary relationships, but indicate that much higher levels of taxonomic
      sampling are necessary for the resolution of family and superfamily
      relationships.

PMID- 22360781
TI  - Bilateral uveal metastasis of a subcutaneous fibrosarcoma in a cat.
AB  - A 6-year-old neutered male domestic short-haired cat was presented to the
      Comparative Ophthalmology service at Michigan State University with a 3-week
      history of decreased appetite and redness of the left eye. The left forelimb had
      been removed 15 months previously because of the presence of a subcutaneous
      fibrosarcoma. In the left globe, a large iridal mass was associated with
      increased intraocular pressure and retinal detachment. A smaller mass involving
      the right iris was also present. Imaging revealed a 2-cm mass in the left
      caudodorsal lung lobe, and abdominal ultrasound showed multifocal bilateral renal
      masses. Aspirates of these masses were nondiagnostic. The left globe was removed
      for palliative reasons, and histopathology showed that fibrosarcoma was
      infiltrating the iris, choroid, and optic nerve. Despite systemic chemotherapy
      with doxorubicin, the animal died 4 months after initial presentation.
      Histopathology confirmed highly angioinvasive metastatic fibrosarcoma also in the
      right uveal tract, the lungs, and both kidneys.

PMID- 22360782
TI  - Give sorrow words.

PMID- 22360783
TI  - Clean nanotube unzipping by abrupt thermal expansion of molecular nitrogen:
      graphene nanoribbons with atomically smooth edges.
AB  - We report a novel physicochemical route to produce highly crystalline nitrogen
      doped graphene nanoribbons. The technique consists of an abrupt N(2) gas
      expansion within the hollow core of nitrogen-doped multiwalled carbon nanotubes
      (CN(x)-MWNTs) when exposed to a fast thermal shock. The multiwalled nanotube
      unzipping mechanism is rationalized using molecular dynamics and density
      functional theory simulations, which highlight the importance of open-ended
      nanotubes in promoting the efficient introduction of N(2) molecules by capillary
      action within tubes and surface defects, thus triggering an efficient and
      atomically smooth unzipping. The so-produced nanoribbons could be few-layered
      (from graphene bilayer onward) and could exhibit both crystalline zigzag and
      armchair edges. In contrast to methods developed previously, our technique
      presents various advantages: (1) the tubes are not heavily oxidized; (2) the
      method yields sharp atomic edges within the resulting nanoribbons; (3) the
      technique could be scaled up for the bulk production of crystalline nanoribbons
      from available MWNT sources; and (4) this route could eventually be used to unzip
      other types of carbon nanotubes or intercalated layered materials such as BN,
      MoS(2), WS(2), etc.

PMID- 22360784
TI  - White matter microstructural changes of thalamocortical networks in
      photosensitivity and idiopathic generalized epilepsy.
AB  - PURPOSE: Photosensitivity or photoparoxysmal response (PPR) is an
      electroencephalography trait that is highly associated with idiopathic
      generalized epilepsies (IGEs) and characterized by changes in cortical
      excitability in response to photic stimulation. Studying functional and
      structural changes of PPR might provide important insights into the pathogenesis
      of IGE. Recent studies revealed a functional network consisting of occipital,
      parietal, and precentral areas that might be implicated in PPR. Herein, we
      investigate the microstructural changes associated with PPR. METHODS: Twelve
      healthy subjects with PPR, nine patients with IGE and PPR (IGE-PPR group), and 18
      healthy controls were studied with diffusion magnetic resonance imaging. Tract
      based spatial statistics were used to test for regional differences in fractional
      anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity
      between groups. KEY FINDINGS: Subjects with PPR exhibited higher FA in the right
      precentral juxtacortical white matter and higher MD in lateral occipital areas
      relative to controls. Patients with IGE-patients showed additional increases in
      regional FA in the thalamus and juxtacortical precentral and parietal areas. Both
      subjects with PPR and patients with IGE-PPR presented axial and radial
      diffusivity changes in the occipital regions. SIGNIFICANCE: Our results show that
      PPR is associated with subcortical microstructural changes in precentral,
      parietal, and occipital regions. The coexistence of PPR and IGE is associated
      with white matter abnormalities in the thalamus and precuneus. PPR and epilepsy
      share similar functional and structural networks in widespread cortical and
      subcortical areas.

PMID- 22360785
TI  - Gait and risk of falls associated with frontal cognitive functions at different
      stages of Alzheimer's disease.
AB  - The decline in frontal cognitive functions contributes to alterations of gait and
      increases the risk of falls in patients with dementia, a category which included
      Alzheimer's disease (AD). The objective of the present study was to compare the
      gait parameters and the risk of falls among patients at different stages of AD,
      and to relate these variables with cognitive functions. This is a cross-sectional
      study with 23 patients with mild and moderate AD. The Clinical Dementia Rating
      was used to classify the dementia severity. The kinematic parameters of gait
      (cadence, stride length, and stride speed) were analyzed under two conditions:
      (a) single task (free gait) and (b) dual task (walking and counting down). The
      risk of falls was evaluated using the Timed Up-and-Go test. The frontal cognitive
      functions were evaluated using the Frontal Assessment Battery (FAB), the Clock
      Drawing Test (CDT) and the Symbol Search Subtest. The patients who were at the
      moderate stage suffered reduced performance in their stride length and stride
      speed in the single task and had made more counting errors in the dual task and
      still had a higher fall risk. Both the mild and the moderate patients exhibited
      significant decreases in stride length, stride speed and cadence in the dual
      task. Was detected a significant correlation between CDT, FAB, and stride speed
      in the dual task condition. We also found a significant correlation between
      subtest Similarities, FAB and cadence in the dual task condition. The dual task
      produced changes in the kinematic parameters of gait for the mild and moderate AD
      patients and the gait alterations are related to frontal cognitive functions,
      particularly executive functions.

PMID- 22360786
TI  - Density functional theory and ab initio studies of the structure and energetics
      of digallium tetraoxide, Ga2O4, in the gas phase.
AB  - A systematic investigation on the neutral and anionic digallium tetraoxide,
      Ga(2)O(4) has been carried out by using density functional theory (DFT), second
      order Moller-Plesset perturbation theory (MP2), and the coupled cluster approach
      with single and double substitutions and a perturbative treatment of the triple
      excitations [CCSD(T)]. The geometry of neutral Ga(2)O(4) has been proposed
      earlier, from an experimental study, to adopt a D(2d) symmetry (J. Phys. Chem.
      1979, 83, 656). However, the current research reveals that, out of the several
      isomers considered for neutral and anionic digallium tetraoxide, the (3)B(1u) and
      (2)B(3g) of the planar D(2h) geometry (7a-D(2h)) are the lowest-energy states for
      Ga(2)O(4) and Ga(2)O(4)(-). Our computations rule out the D(2d) geometry (3
      D(2d)) as a viable contender for neutral Ga(2)O(4). The (3)B(2) (3-D(2d)) state
      is located above the (3)B(1u) (7-D(2h)) state by at least 4.26 eV. The energies
      of the low lying states, geometrical parameters, and energetic features (VEDE,
      AEDE, and AEA) are reported. The AEA of Ga(2)O(4) is calculated to be 3.94 eV
      (B3LYP), 3.24 eV (MP2), 3.42 eV [CCSD(T)//B3LYP], and 3.38 eV [CCSD(T)//MP2],
      respectively. In addition, the dissociation energy, D(e), for the process
      Ga(2)O(4) ((3)B(1u)) -> 2GaO(2) ((2)A(2)) is 3.59 eV (B3LYP), 5.08 eV (MP2), 4.82
      eV [CCSD(T)//B3LYP], and 4.80 eV [CCSD(T)//MP2]. The results obtained in this
      work are critically analyzed, discussed, and compared with those of the analogous
      metal oxides.

PMID- 22360787
TI  - Does anticoagulation in Eisenmenger syndrome impact long-term survival?
AB  - OBJECTIVE: To determine the impact of anticoagulation on survival in Eisenmenger
      syndrome. BACKGROUND: The use of anticoagulation for primary prevention of
      adverse events in patients with Eisenmenger syndrome has been proposed but not
      studied. Strong arguments have been made both for and against anticoagulation
      based on the known risk of hemoptysis and pulmonary vascular thrombosis. DESIGN
      AND SETTING: Retrospective cohort study at a tertiary referral hospital. PATIENTS
      AND INTERVENTIONS:   One hundred forty-four patients with established Eisenmenger
      physiology all underwent initial laboratory, echocardiographic, and
      catheterization evaluation after initial referral. We retrospectively identified
      patients who were started on anticoagulation (AC) and compared them to patients
      who did not receive anticoagulation therapy (non-AC). Baseline variables were
      compared between groups, as well as between survivors and nonsurvivors. Analyses
      of prognostic factors and survival were done using Cox and Kaplan-Meier methods.
      OUTCOME MEASURES: The primary outcome was death since time of baseline
      evaluation. RESULTS: We identified 48 anticoagulated and 44 non-anticoagulated
      patients with Eisenmenger physiology (oxygen saturation 82 +/- 9%, PaO(2) 48 +/-
      8 mm Hg, hemoglobin 18.6 +/- 4 g/dL). More atrial septal defect patients were in
      the AC group, but there were no other baseline differences in clinical,
      functional, or hemodynamic data. After mean follow-up of 7 +/- 5.4 years (range 1
      31), 11 patients died in the AC and 10 died in the non-AC group. There was no
      survival difference between groups (log rank test = 1.78; P is not significant).
      For the entire cohort, mortality was significantly associated with New York Heart
      Association class 3-4 (hazard ratio = 4.2), evidence of right heart failure
      (hazard ratio = 13.6), and a mean corpuscular volume <80 fL (hazard ratio = 3.8).
      Use of anticoagulation did not impact survival. Bleeding complications occurred
      in seven (16%) of AC patients, including two fatalities. CONCLUSIONS:
      Anticoagulation had no impact on long-term survival in this limited study. These
      data may be useful in considering future studies addressing this question.

PMID- 22360788
TI  - Provider and clinic-level correlates of deferring antiretroviral therapy for
      people who inject drugs: a survey of North American HIV providers.
AB  - BACKGROUND: Injection drug users (IDUs) face numerous obstacles to receiving
      optimal HIV care, and have been shown to underutilize antiretroviral therapy
      (ART). We sought to estimate the degree to which providers of HIV care defer
      initiation of ART because of injection drug use and to identify clinic and
      provider-level factors associated with resistance to prescribing ART to IDUs.
      METHODS: We administered an Internet-based survey to 662 regular prescribers of
      ART in the United States and Canada. Questionnaire items assessed characteristics
      of providers' personal demographics and training, site of clinical practice and
      attitudes about drug use. Respondents then rated whether they would likely
      prescribe or defer ART for hypothetical patients in a series of scenarios
      involving varying levels of drug use and HIV disease stage. RESULTS: Survey
      responses were received from 43% of providers invited by email and direct mail,
      and 8.5% of providers invited by direct mail only. Overall, 24.2% of providers
      reported that they would defer ART for an HIV-infected patient with a CD4+ cell
      count of 200 cells/mm3 if the patient actively injected drugs, and 52.4% would
      defer ART if the patient injected daily. Physicians were more likely than non
      physician providers to defer ART if a patient injected drugs (adjusted odds ratio
      2.6, 95% CI 1.4-4.9). Other predictors of deferring ART for active IDUs were
      having fewer years of experience in HIV care, regularly caring for fewer than 20
      HIV-infected patients, and working at a clinic serving a population with low
      prevalence of injection drug use. Likelihood of deferring ART was directly
      proportional to both CD4+ cell count and increased frequency of injecting.
      CONCLUSIONS: Many providers of HIV care defer initiation of antiretroviral
      therapy for patients who inject drugs, even in the setting of advanced
      immunologic suppression. Providers with more experience of treating HIV, those in
      high injection drug use prevalence areas and non-physician providers may be more
      willing to prescribe ART despite on-going injection drug use. Because of
      limitations, including low response rate and use of a convenience sample, these
      findings may not be generalizable to all HIV care providers in North America.

PMID- 22360789
TI  - Remembering and diagnosing clients: does experience matter?
AB  - Experienced mental health clinicians often do not outperform novices in
      diagnostic decision making. In this paper we look for an explanation of this
      phenomenon by testing differences in memory processes. In two studies we aimed to
      look at differences in accuracy of diagnoses in relation to free recall of client
      information between mental health clinicians with different levels of experience.
      Clinicians were presented with two cases, and were asked afterwards, either
      directly (Study 1) or after 1 week (Study 2), to give the appropriate diagnoses
      and to write down what they remembered of the cases. We found in Study 1 that the
      accuracy of the diagnoses was the same for all levels of experience, as was the
      amount of details recalled. Very experienced clinicians did remember more higher
      order concepts, that is, abstractions from the presented information. In Study 2
      we found that the very experienced clinicians were less accurate in their
      diagnoses and remembered fewer details than the novices. In response to these
      findings we further discuss their implications for psychodiagnostic practice.

PMID- 22360790
TI  - Improving classical substructure-based virtual screening to handle extrapolation
      challenges.
AB  - Target-oriented substructure-based virtual screening (sSBVS) of molecules is a
      promising approach in drug discovery. Yet, there are doubts whether sSBVS is
      suitable also for extrapolation, that is, for detecting molecules that are very
      different from those used for training. Herein, we evaluate the predictive power
      of classic virtual screening methods, namely, similarity searching using Tanimoto
      coefficient (MTC) and Naive Bayes (NB). As could be expected, these classic
      methods perform better in interpolation than in extrapolation tasks.
      Consequently, to enhance the predictive ability for extrapolation tasks, we
      introduce the Shadow approach, in which inclusion relations between substructures
      are considered, as opposed to the classic sSBVS methods that assume independence
      between substructures. Specifically, we discard contributions from substructures
      included in ("shaded" by) others which are, in turn, included in the molecule of
      interest. Indeed, the Shadow classifier significantly outperforms both MTC
      (pValue = 3.1 * 10(-16)) and NB (pValue = 3.5 * 10(-9)) in detecting hits sharing
      low similarity with the training active molecules.

PMID- 22360791
TI  - An interview with the authors of Did AIM-HIGH aim too low. Interview by Jinghong
      Xu.

PMID- 22360793
TI  - Synthesis of mono- and bisadducts of thieno-o-quinodimethane with C60 for
      efficient polymer solar cells.
AB  - A series of mono- and bisadducts of thieno-o-quinodimethane with C(60) (TOQC) was
      efficiently prepared through the Diels-Alder reaction of pristine or solubilizing
      side-chain-substituted 2,3-bis(chloromethyl)thiophene with C(60). The pristine
      TOQC bisadduct (bis-TOQC) shows much higher performance than the side-chain
      substituted TOQC bisadducts in polymer solar cells, while the situation is
      inverse for the TOQC monoadducts. The best power conversion efficiency of 5.1%
      was achieved from the bis-TOQC:P3HT solar cells under simulated AM1.5G
      irradiation (86 mW/cm(2)).

PMID- 22360794
TI  - Aging and consumer decision making.
AB  - Research on consumer decision making and aging is especially important for
      fostering a better understanding of ways to maintain consumer satisfaction and
      high decision quality across the life span. We provide a review of extant
      research on the effects of normal aging on cognition and decision processes and
      how these age-related processes are influenced by task environment,
      meaningfulness of the task, and consumer expertise. We consider how research
      centered on these topics generates insights about changes in consumption
      decisions that occur with aging and identify a number of gaps and directions for
      future research.

PMID- 22360795
TI  - Pain questionnaire development focusing on cross-cultural equivalence to the
      original questionnaire: the Japanese version of the Short-Form McGill Pain
      Questionnaire.
AB  - OBJECTIVES: The present study aimed to develop a Japanese version of the Short
      Form McGill Pain Questionnaire (SF-MPQ-J) that focuses on cross-culturally
      equivalence to the original English version and to test its reliability and
      validity. DESIGN: Cross-sectional design. METHOD: In study 1, SF-MPQ was
      translated and adapted into Japanese. It included construction of response scales
      equivalent to the original using a variation of the Thurstone method of equal
      appearing intervals. A total of 147 undergraduate students and 44 pain patients
      participated in the development of the Japanese response scales. To measure the
      equivalence of pain descriptors, 62 pain patients in four diagnostic groups were
      asked to choose pain descriptors that described their pain. In study 2, chronic
      pain patients (N=126) completed the SF-MPQ-J, the Long-Form McGill Pain
      Questionnaire Japanese version (LF-MPQ-J), and the 11-point numerical rating
      scale of pain intensity. Correlation analysis examined the construct validity of
      the SF-MPQ-J. RESULTS: The results from study 1 were used to develop SF-MPQ-J,
      which is linguistically equivalent to the original questionnaire. Response scales
      from SF-MPQ-J represented the original scale values. All pain descriptors, except
      one, were used by >33% in at least one of the four diagnostic groups. Study 2
      exhibited adequate internal consistency and test-retest reliability, with the
      construct validity of SF-MPQ-J comparable to the original. CONCLUSION: These
      findings suggested that SF-MPQ-J is reliable, valid, and cross-culturally
      equivalent to the original questionnaire. Researchers might consider using this
      scale in multicenter, multi-ethnical trials or cross-cultural studies that
      include Japanese-speaking patients.

PMID- 22360796
TI  - The lipid alterations in the stratum corneum of dogs with atopic dermatitis are
      alleviated by topical application of a sphingolipid-containing emulsion.
AB  - BACKGROUND: Atopic dermatitis (AD) results from an altered skin barrier
      associated with defects in the lipid composition of the skin. Dogs with AD
      present similar clinical symptoms to humans, and may be a useful model for
      investigations into AD. AIM: To analyse the changes occurring in the lipids of
      the stratum corneum (SC) of dogs with AE after 3 weeks of topical treatment with
      an emulsion containing ceramides, free fatty acids (FFAs) and cholesterol (skin
      lipid complex; SLC). METHODS: Nonlesional SC was collected by tape stripping from
      control and treated areas. Free and protein-bound lipids were purified, and the
      various classes were isolated by column chromatography, analysed by thin-layer
      chromatography and assayed. RESULTS: Ceramides, FFA and cholesterol were all
      found to be lower in the skin of untreated dogs with AD than in normal dogs, and
      the topical treatment resulted in significantly increased values for ceramides.
      Conversely, only trace amounts of glucosylceramides were present in normal SC,
      but a high concentration (27 MUg per mg protein) was detected in canine atopic
      SC, which disappeared after treatment with SLC. There was a heterogeneous
      distribution of all of the lipids in the different layers of canine atopic SC,
      which was more pronounced for protein-bound than for free lipids. Following
      topical treatment, the protein-bound lipid content normalized. CONCLUSIONS:
      Topical treatment with SLC resulted in a significant improvement of the lipid
      biosynthesis of keratinocytes in atopic dogs, thereby potentially enabling the
      formation of a tighter epidermal barrier.

PMID- 22360797
TI  - Chemical constituents of the hemiparasitic plant Phoradendron brachystachyum DC
      Nutt (Viscaceae).
AB  - Phoradendron brachystachyum is a hemiparasitic plant widely distributed in Mexico
      that belongs to the Viscaceae family. It has been commonly used in folk medicine
      as a substitute for the European mistletoe. In this chemical study, morolic acid
      was isolated as the major component (47.54% of the total composition of acetone
      extract) of this plant. In addition, 19 known compounds were identified: beta
      sitosteryl and stigmasteryl linoleates, beta-sitosterol, stigmasterol,
      triacontanol, squalene, alpha- and beta-amyrin, lupeol, lupenone, betulin
      aldehyde, betulon aldehyde, oleanolic aldehyde, betulinic acid, betulonic acid,
      moronic acid, morolic acid, oleanolic acid, flavonoids acacetin and acacetin 7
      methyl ether. There have been no previous reports in the literature on the
      chemical composition of this potential natural source of hypoglycaemic and
      antihypertensive compounds.

PMID- 22360798
TI  - Environmental and health impacts of Canada's bitumen industry: in search of
      answers.

PMID- 22360799
TI  - A high blood level in the air trap reduces microemboli during hemodialysis.
AB  - Previous studies have demonstrated the presence of air microemboli in the
      dialysis circuit and in the venous circulation of the patients during
      hemodialysis. In vitro studies indicate that a high blood level in the venous air
      trap reduces the extent of microbubble formation. The purpose of this study was
      to examine whether air microbubbles can be detected in the patient's access and
      if so, whether the degree of microbubble formation can be altered by changing the
      blood level in the venous air trap. This was a randomized, double-blinded,
      interventional study of 20 chronic hemodialysis patients. The patients were
      assigned to hemodialysis with either an elevated or a low blood level in the air
      trap. The investigator and the patient were blinded to the settings. The numbers
      of microbubbles were measured at the site of the arteriovenous (AV) access for 2
      min with the aid of an ultrasonic Doppler device. The blood level in the air trap
      was then altered to the opposite setting and a new measurement was carried out
      after an equilibration period of 30 min. Median (range) for the number of
      microbubbles measured with the high air trap level and the low air trap level in
      AV access was 2.5 (0-80) compared with 17.5 (0-77), respectively (P = 0.044). The
      degree of microbubble formation in hemodialysis patients with AV access was
      reduced significantly if the blood level in the air trap was kept high. The
      exposure of potentially harmful air microbubbles was thereby significantly
      reduced. This measure can be performed with no additional healthcare cost.

PMID- 22360801
TI  - Host risk factors for the development of multiple non-melanoma skin cancers.
AB  - Non-melanoma skin cancer (NMSC) is the most common cancer in the US, and having
      multiple lesions conveys substantial cost and morbidity for the individual
      involved. Although there are data available on risk factors for NMSC, there are
      currently few studies that identify specific risk factors for development of
      multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men
      (Health Professionals Follow-up Study) and women (Nurses' Health Study). Compared
      with individuals with a single NMSC, having greater number of sunburns was a risk
      factor for developing >= 2 NMSCs [>= 10 sunburns, cumulative relative risk (RR) =
      1.21, 95% confidence interval (CI): 1.07-1.36] and a higher risk of developing >=
      11 NMSCs (>=10 sunburns, RR = 2.33, 95% CI: 1.57-3.46). Inability-to-tan was
      associated with risk of developing >= 2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18
      1.40) and a higher risk of developing >= 11 NMSCs (RR = 1.91, 95% CI: 1.50-2.43).
      Men had an increased risk of developing >= 2 NMSCs (cumulative RR = 1.53, 95% CI:
      1.40-1.66). Risk of developing 2-4, 5-10 and >=11 NMSCs increased with age. Other
      risk factors for developing >= 2 NMSCs included red natural hair colour
      (cumulative RR = 1.23, 95% CI: 1.07-1.42), family history of melanoma (cumulative
      RR = 1.15, 95% CI: 1.03-1.28), and having >= 6 nevi on the left arm (cumulative
      RR = 1.22, 95% CI: 1.07-1.40). In conclusion, physicians caring for individuals
      with incident NMSCs may consider paying special attention to those at highest
      risk for developing additional tumours, especially males and those with a history
      of >= 10 lifetime sunburns, by performing routine full skin examinations and
      counselling for aggressive photoprotection.

PMID- 22360803
TI  - The trouble with men.

PMID- 22360804
TI  - En bloc transurethral resection of bladder lesions: a trick to retrieve specimens
      up to 4.5 cm.
AB  - The present technique maintains the integrity of voluminous lesions during
      extraction. Pathological analysis is consequently improved and a proper
      evaluation of the surgical margins is also possible. Papillary lesions of up to
      4.5 cm are amenable to en bloc resection and extraction, while solid lesions
      comply less well with the urethra and sometimes are very difficult to extract.
      Nevertheless, the main limitation of the technique remains that lesions
      originating from the bladder neck are not amenable to en bloc resection,while
      particular attention should be paid during resection of lesions involving the
      ureteric orifice to avoid ureteric stripping.

PMID- 22360800
TI  - Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids:
      importance of the mitochondrial function.
AB  - Insulin resistance condition is associated to the development of several
      syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome.
      Although the factors linking insulin resistance to these syndromes are not
      precisely defined yet, evidence suggests that the elevated plasma free fatty acid
      (FFA) level plays an important role in the development of skeletal muscle insulin
      resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and
      myocytes to physiological concentrations of saturated fatty acids is associated
      with insulin resistance condition. Several mechanisms have been postulated to
      account for fatty acids-induced muscle insulin resistance, including Randle
      cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we
      reviewed experimental evidence supporting the involvement of each of these
      propositions in the development of skeletal muscle insulin resistance induced by
      saturated fatty acids and propose an integrative model placing mitochondrial
      dysfunction as an important and common factor to the other mechanisms.

PMID- 22360806
TI  - New treatment paradigm for prostate cancer: abarelix initiation therapy for
      immediate testosterone suppression followed by a luteinizing hormone-releasing
      hormone agonist.

PMID- 22360807
TI  - Coronary stent management in elective genitourinary surgery.

PMID- 22360810
TI  - Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for
      lipogenesis in hypoxic melanoma cells.
AB  - The tricarboxylic acid (TCA) cycle is the central hub of oxidative metabolism,
      running in the classic forward direction to provide carbon for biosynthesis and
      reducing agents for generation of ATP. Our metabolic tracer studies in melanoma
      cells showed that in hypoxic conditions the TCA cycle is largely disconnected
      from glycolysis. By studying the TCA branch point metabolites, acetyl CoA and
      citrate, as well as the metabolic endpoint glutamine and fatty acids, we
      developed a comprehensive picture of the rewiring of the TCA cycle that occurs in
      hypoxia. Hypoxic tumor cells maintain proliferation by running the TCA cycle in
      reverse. The source of carbon for acetyl CoA, citrate, and fatty acids switches
      from glucose in normoxia to glutamine in hypoxia. This hypoxic flux from
      glutamine into fatty acids is mediated by reductive carboxylation. This reductive
      carboxylation is catalyzed by two isocitrate dehydrogenases, IDH1 and IDH2. Their
      combined action is necessary and sufficient to effect the reverse TCA flux and
      maintain cellular viability.

PMID- 22360811
TI  - Rhodium-catalyzed C-H bond activation/[4 + 2] annulation/aromatization cascade to
      produce phenol, naphthol, phenanthrenol, and triphenylenol derivatives.
AB  - It has been established that a cationic rhodium(I)/dppp complex catalyzes the
      aldehyde C-H bond activation/[4 + 2] annulation/aromatization cascade to produce
      phenol, naphthol, phenanthrenol, and triphenylenol derivatives from readily
      available conjugated alkynyl aldehydes and alkynes.

PMID- 22360812
TI  - Estimating age-specific influenza-related hospitalization rates during the
      pandemic (H1N1) 2009 in Davidson Co, TN.
AB  - BACKGROUND: In April 2009, a pandemic caused by a novel influenza strain, the
      A(H1N1)pdm09 virus, started. Few age-specific estimates of hospitalizations
      associated with the first year of circulation of the pandemic virus are
      available. OBJECTIVES: To estimate age-specific hospitalization rates associated
      with laboratory-confirmed A(H1N1)pdm09 virus in Davidson County, TN, from May
      2009 to March 2010. PATIENTS/METHODS: Two separate strategies were applied:
      capture-recapture and surveillance-sampling methods. For the capture-recapture
      estimates, we linked data collected via two independent prospective population
      based surveillance systems: The Influenza Vaccine Effectiveness Network (Flu-VE)
      tested consenting county patients hospitalized with respiratory symptoms at
      selected hospitals using real-time reverse transcriptase polymerase chain
      reaction (rRT-PCR); the Emerging Infections Program identified county patients
      with positive influenza tests in all area hospitals. For the surveillance
      sampling estimates, we applied the age-specific proportions of influenza-positive
      patients (from Flu-VE) to the number of acute respiratory illness
      hospitalizations obtained from the Tennessee Hospital Discharge Data system.
      RESULTS: With capture-recapture, we estimated 0.89 (95% CI, 0.72-1.49), 0.62
      (0.42-1.11), 1.78 (0.99-3.63), and 0.76 (0.50-1.76) hospitalizations per 1000
      residents aged < 5, 5-17, 18-49, and >= 50 years, respectively. Surveillance
      sampling estimated rates were 0.78 (0.46-1.22), 0.32 (0.14-0.69), 0.99 (0.64
      1.52), and 1.43 (0.80-2.48) hospitalizations per 1000 residents aged <5, 5-17, 18
      49, and >= 50 years, respectively. In all age-groups combined, we estimated
      approximately 1 influenza-related hospitalization per 1000 residents.
      CONCLUSIONS: Two independent methods provided consistent results on the burden of
      pandemic virus in Davidson County and suggested that the overall incidence of
      A(H1N1)pdm09-associated hospitalization was 1 per 1000 county residents.

PMID- 22360813
TI  - Effects of acute and chronic inflammation on proteins involved in duodenal iron
      absorption in mice: a time-course study.
AB  - In order to understand better the molecular mechanisms involved in the
      pathogenesis of anaemia of inflammation, we carried out a time-course study on
      the effects of turpentine-induced acute and chronic inflammation on duodenal
      proteins involved in Fe absorption in mice. Expression levels of these proteins
      and hepatic hepcidin and serum Fe levels were determined in inflamed mice. In
      acutely inflamed mice, significantly increased expression of ferritin was the
      earliest change observed, followed by decreased divalent metal transporter 1
      expression in the duodenum and increased hepcidin expression in the liver.
      Ferroportin expression increased subsequently, despite high levels of hepcidin.
      Hypoferraemia, which developed at early time periods studied, was followed by
      increased serum Fe levels at later points. The present results thus show that
      acute inflammation induced several changes in the expression of proteins involved
      in duodenal Fe absorption, contributing to the development of hypoferraemia.
      Resolution of inflammation caused attenuation of many of these effects. Effects
      in chronically inflamed mice were less consistent. The present results also
      suggest that inflammation-induced increases in ferritin appeared to override the
      effects of hepcidin on the expression levels of ferroportin in enterocytes.

PMID- 22360814
TI  - Controlled synthesis of Pd-Pt alloy hollow nanostructures with enhanced catalytic
      activities for oxygen reduction.
AB  - Pd-Pt alloy nanocrystals (NCs) with hollow structures such as nanocages with
      porous walls and dendritic hollow structures and Pd@Pt core-shell dendritic NCs
      could be selectively synthesized by a galvanic replacement method with uniform Pd
      octahedral and cubic NCs as sacrificial templates. Fine control over the degree
      of galvanic replacement of Pd with Pt allowed the production of Pd-Pt NCs with
      distinctly different morphologies. The synthesized hollow NCs exhibited
      considerably enhanced oxygen reduction activities compared to those of Pd@Pt core
      shell NCs and a commercial Pt/C catalyst, and their electrocatalytic activities
      were highly dependent on their morphologies. The Pd-Pt nanocages prepared from
      octahedral Pd NC templates exhibited the largest improvement in catalytic
      performance. We expect that the present work will provide a promising strategy
      for the development of efficient oxygen reduction electrocatalysts and can also
      be extended to the preparation of other hybrid or hetero-nanostructures with
      desirable morphologies and functions.

PMID- 22360815
TI  - Cotard's syndrome with glioblastoma multiforme.
AB  - OBJECTIVE: Brain tumors are classically associated with neurological and/or
      psychiatric symptomatology. Behavioral or cognitive disorders can underlie
      delirium, personality changes, psychotic reactions, and mood disorders. METHOD:
      To illustrate this, we report the case of a 60-year-old male patient confronted
      with an inoperable glioblastoma multiforme on the splenium of the corpus
      callosum, of poor prognosis, treated by concomitant radiochemotherapy with
      temozolomide, who developed psychotic depression with Cotard's syndrome. Clinical
      manifestations of this syndrome with untoward consequences in terms of prognosis
      are classically characterized by intense moral suffering, indignity and
      pessimistic fixations, suicidal ideations, and a nihilistic delusion relating to
      one's own body. RESULTS: Nevertheless, this association between Cotard's syndrome
      and glioblastoma has been seldom described. To our knowledge, this is the first
      time that this has been described as a complication of this particular tumor
      location. Some neuropsychopathological hypotheses are proposed, which involve
      medical, iatrogenic, and psychogenesis issues. SIGNIFICANCE OF RESULTS: This case
      report points to the necessary collaboration between psychiatrists, neuro
      oncologists and radiation oncologists in improving the patient's management and
      quality of life.

PMID- 22360816
TI  - Electrocardiographic predictors of out-of-hospital sudden cardiac arrest in
      patients with coronary artery disease.
AB  - Sudden cardiac arrest (SCA), due mainly to coronary artery disease (CAD), is a
      leading cause of death. To identify electrocardiographic and clinical differences
      between patients with CAD with and without SCA, 87 victims of SCA with CAD were
      compared with 131 patients with CAD without SCA. Patients' latest routine
      electrocardiograms and clinical variables were compared. Patients with CAD with
      and without previous myocardial infarctions (MIs) were included. Patients with
      SCA had a higher incidence of echocardiographic evidence of left ventricular
      hypertrophy and/or heart failure than controls. The median left ventricular
      ejection fractions for patients with SCA with and without previous MIs were 0.30
      (interquartile range 0.24 to 0.41) and 0.41 (interquartile range 0.25 to 0.56).
      The median time between the last electrocardiographic assessment and SCA was 59
      days (interquartile range 29 to 137). Regarding electrocardiographic
      characteristics, in patients with and without previous MIs, QRS width (odds ratio
      1.032, 95% confidence interval 1.012 to 1.053, p = 0.002, and odds ratio 1.035,
      95% confidence interval 1.015 to 1.056, p = 0.001) was the only significant
      predictor of SCA. In conclusion, in patients with CAD, regardless of a previous
      MI, a longer QRS width and echocardiographic parameters consistent with heart
      failure are associated with SCA, even in patients with ischemic cardiomyopathy
      currently not eligible for an implantable cardioverter-defibrillator.

PMID- 22360817
TI  - Congenital long QT 3 in the pediatric population.
AB  - There is insufficient knowledge concerning long-QT (LQT) 3 in the pediatric
      population to determine whether recommendations for more aggressive therapy in
      these patients are appropriate. An international multicenter review of 43
      children with cardiac sodium channel (SCN5A) mutations and clinical
      manifestations of LQT syndrome without overlap of other SCN5A syndromes was
      undertaken to describe the clinical characteristics of LQT3 in children. Patients
      were aged 7.6 +/- 5.9 years at presentation and were followed for 4.7 +/- 3.9
      years. There was significant intrasubject corrected QT interval (QTc) variability
      on serial electrocardiography. Forty-two percent presented with severe symptoms
      or arrhythmia and exhibited longer QTc intervals compared to asymptomatic
      patients. None of the 14 patients who underwent primary prevention implantable
      cardioverter-defibrillator (ICD) implantation received appropriate shocks in 41
      patient-years of follow-up, while 2 of 6 patients who underwent secondary
      prevention ICD implantation received appropriate shocks in 30 patient-years of
      follow-up. Half of patients who underwent ICD implantation experienced
      inappropriate shocks or ICD-related complications. Mexiletine significantly
      shortened the QTc interval, and QTc shortening was greater in patients with
      longer pretreated QTc intervals. Two ICD patients with frequent appropriate ICD
      shocks showed immediate clinical improvement, with elimination of appropriate ICD
      shocks after mexiletine loading. In conclusion, severe symptoms are common in
      children with LQT3 and are associated with longer QTc intervals. ICD implantation
      is associated with significant morbidity. Mexiletine shortens the QTc interval,
      and it may be beneficial.

PMID- 22360818
TI  - Comparison of baseline predictors of prognosis in pulmonary arterial hypertension
      in patients surviving <=2 years and those surviving >=5 years after baseline
      right-sided cardiac catheterization.
AB  - Idiopathic pulmonary arterial hypertension (PAH) is usually associated with a
      poor outcome but the prognosis with other forms of PAH is not well-described.
      Advances in therapy have furthered clouded the disease course. We sought to
      determine the baseline indicators of prognosis in patients with PAH. We reviewed
      the records of patients with PAH followed up at our institution to identify those
      who died within 2 years (reduced survival group; n = 21) and those who survived
      >5 years (long survival group; n = 60). The groups were compared for prognostic
      significance of the baseline clinical parameters. The reduced survival group were
      older (p = 0.001) and more likely to have scleroderma-associated PAH (p = 0.01),
      have pericardial effusion (p = 0.01), have a shorter 6-minute walk test (6MWT)
      distance (p = 0.001), to require oxygen during 6MWT (p = 0.02), have a worse
      World Health Organization functional class (p <0.001), and have greater serum
      brain natriuretic peptide levels (p = 0.01). Regression analysis showed age,
      World Health Organization functional class, 6MWT distance, the need for oxygen
      during the 6MWT, and renal disease to be independently associated with a poor
      prognosis. In conclusion, age, PAH etiology, World Health Organization functional
      class, pericardial effusion, 6MWT distance, the need for oxygen during the 6MWT,
      and brain natriuretic peptide are predictors of prognosis in patients PAH
      receiving specific therapy and might help identify a group that could benefit
      from aggressive upfront therapy.

PMID- 22360819
TI  - CHADS2 and CHA2DS2-VASc risk factors to predict first cardiovascular
      hospitalization among atrial fibrillation/atrial flutter patients.
AB  - Limited data exist concerning risk factors for cardiovascular (CV)
      hospitalization in patients with atrial fibrillation (AF) or atrial flutter
      (AFL). The aim of this retrospective cohort evaluation was to assess whether
      patient characteristics and risk factors, including CHADS(2) (congestive heart
      failure, hypertension, age >=75 years, type 2 diabetes, and previous stroke or
      transient ischemic attack [doubled]) and CHA(2)DS(2)-VASc (congestive heart
      failure; hypertension; age >=75 years [doubled]; type 2 diabetes; previous
      stroke, transient ischemic attack, or thromboembolism [doubled]; vascular
      disease; age 65 to 75 years; and sex category) scores, identified patients with
      AF or AFL at risk for CV hospitalization. Claims data (January 2003 to June 2009)
      were evaluated to identify patients aged >=40 years with >=1 inpatient or >=2
      (within 30 days of each other) outpatient diagnoses of AF or AFL and an absence
      of diagnosis codes related to cardiac surgery within 30 days of AF or AFL
      diagnosis. Risk factors for first CV hospitalization in the 2-year period after
      diagnosis were assessed using univariate and multivariate analyses. Overall,
      377,808 patients (mean age 73.9 +/- 12.1 years) were identified, of whom 128,048
      had CV hospitalizations. CHADS(2) and CHA(2)DS(2)-VASc scores were the top 2
      predictors of first CV hospitalization after AF or AFL diagnosis. Hospitalization
      risk was increased 2.3- to 2.7-fold in patients with CHADS(2) scores of 6 and
      approximately 3.0-fold in patients with CHA(2)DS(2)-VASc scores of 9 compared to
      patients with a score of 0. These increases were maintained essentially unchanged
      throughout the 2-year follow-up period. In conclusion, CHADS(2) and CHA(2)DS(2)
      VASc scores were predictive of first CV hospitalization in patients with AF or
      AFL and may be helpful in identifying "at-risk" patients and guiding therapy.

PMID- 22360820
TI  - Comparison of lipid-modifying efficacy of rosuvastatin versus atorvastatin in
      patients with acute coronary syndrome (from the LUNAR study).
AB  - Patients with acute coronary syndrome are recommended for early aggressive low
      density lipoprotein (LDL) cholesterol-lowering therapy. The LUNAR study compared
      the efficacy of rosuvastatin with that of atorvastatin in decreasing LDL
      cholesterol in patients with acute coronary syndrome. Adult patients with
      coronary artery disease who were hospitalized for an acute coronary syndrome
      within 48 hours of first symptoms were randomized (n = 825) to an open-label,
      once-daily treatment with rosuvastatin 20 mg (RSV20), rosuvastatin 40 mg (RSV40),
      or atorvastatin 80 mg (ATV80) for 12 weeks. Patients were evaluated at weeks 2,
      6, and 12. The primary end point was treatment efficacy in lowering LDL
      cholesterol averaged over 6 to 12 weeks. Changes in other lipoproteins, including
      high-density lipoprotein (HDL) cholesterol, and safety were evaluated. Analysis
      of covariance was used to compare least squares mean differences between each
      rosuvastatin treatment arm and the atorvastatin arm. The efficacy of RSV40 in
      lowering LDL cholesterol was significantly greater than that of ATV80 (46.8% vs
      42.7% decrease, p = 0.02). LDL cholesterol lowering by RSV20 was similar to that
      by ATV80. Increases in HDL cholesterol were significantly greater with RSV40
      (11.9%, p <0.001) and RSV20 (9.7%, p <0.01) than with ATV80 (5.6%). RSV40 was
      also significantly more effective than ATV80 in improving most other secondary
      efficacy variables, whereas the effects of RSV20 on these parameters were
      generally similar to those of ATV80. All 3 treatments were generally well
      tolerated over 12 weeks. In conclusion, results from the LUNAR study show that
      RSV40 more effectively decreased LDL cholesterol, increased HDL cholesterol, and
      improved other blood lipid parameters than ATV80 in patients with acute coronary
      syndrome.

PMID- 22360821
TI  - Transcriptionally-active high-risk human papillomavirus is rare in oral cavity
      and laryngeal/hypopharyngeal squamous cell carcinomas--a tissue microarray study
      utilizing E6/E7 mRNA in situ hybridization.
AB  - AIMS: Human papillomavirus is well established in oropharyngeal squamous cell
      carcinoma as both causative and prognostic, but its significance in non
      oropharyngeal tumours is unclear. In particular, the significance of finding
      viral DNA is not known. We sought to evaluate nonoropharyngeal squamous cell
      carcinomas for transcriptionally-active human papillomavirus and to compare this
      with the presence of viral DNA. METHODS: We evaluated an 87 patient tissue
      microarray cohort of oral cavity and laryngeal/hypopharyngeal squamous cell
      carcinomas for high risk human papillomavirus DNA and E6 and E7 mRNA transcripts
      by in situ hybridization, and for p16 expression by immunohistochemistry.
      RESULTS: We found only two of the 73 (2.7%) evaluable cases to harbour
      transcriptionally-active human papillomavirus. Both of these tumours were from
      the larynx, one was positive for human papillomavirus DNA by in situ
      hybridization, and both were extensively positive for p16. All oral cavity and
      hypopharyngeal tumours were negative for human papillomavirus. CONCLUSIONS:
      Transcriptionally-active human papillomavirus appears to be rare in laryngeal,
      hypopharyngeal, and oral cavity squamous cell carcinomas. As such, it appears
      unlikely to be a 'driver' or to be clinically significant in most established
      tumours.

PMID- 22360822
TI  - Focal epilepsies in adult patients attending two epilepsy centers: classification
      of drug-resistance, assessment of risk factors, and usefulness of "new"
      antiepileptic drugs.
AB  - PURPOSE: To classify the grade of antiepileptic drug (AED) resistance in a cohort
      of patients with focal epilepsies, to recognize the risk factors for AED
      resistance, and to estimate the helpfulness of "new-generation" AEDs. METHODS: We
      included 1,155 adults with focal epilepsies who were observed consecutively after
      1990 and followed regularly at two epilepsy centers. We systematically collected
      the clinical, diagnostic, and therapeutic data using a custom-written database.
      We classified the patients as seizure-free or AED resistant according to the
      International League Against Epilepsy (ILAE) criteria, and we evaluated the risk
      factors associated with AED resistance using logistic regression analysis. We
      further grouped AED-resistant patients in different grades (I, II, and III)
      according to the number of AEDs already tried as proposed by Perucca. KEY
      FINDINGS: AED resistance occurred in 57.8% of the 729 patients with symptomatic
      focal epilepsies and was positively associated with electroencephalography (EEG)
      abnormalities, seizure type, and the presence of mesial temporal sclerosis. Among
      426 patients without detectable causes, the percentage of AED resistance was
      significantly lower (39.2%) and correlated with EEG abnormalities and psychiatric
      symptoms. Among AED-resistant patients, the majority (64.6%) had tried three or
      more AEDs, which fit the more severe grade III proposed by Perucca. Among seizure
      free patients, more than one-half (57%) needed to try two or more AEDs before
      reaching seizure control (14.9% needed three or more AEDs). Furthermore, among
      seizure-free patients who could be previously classified as resistant to two or
      more AEDs, 52.2% reached seizure freedom while receiving treatment with "new
      generation" AEDs. SIGNIFICANCE: The ILAE classification of AED resistance, as
      well the graded classification proposed by Perucca, was easily exploitable in our
      patients, although these classifications systems appear to have a limited value
      in predicting seizure outcome. Actually, a small but not negligible percentage of
      patients reached seizure freedom after trying several AEDs (including "new"
      AEDs), suggesting repeated trials may be necessary for seizure control.

PMID- 22360823
TI  - Infection by Leishmania amazonensis in mice: a potential model for chronic
      hypoxia.
AB  - Hypoxia is a common feature of injured and infected tissues. Hypoxia inducible
      factors 1alpha and 2alpha (HIF-1alpha, HIF-2alpha) are heterodimeric
      transcription factors mediating the cellular responses to hypoxia and also the
      vascular endothelial growth factor (VEGF). VEGF is a cytokine which can be
      induced by hypoxia, whose pathogenic mechanisms are still unclear and which is
      the subject of debate. Murine cutaneous lesions during Leishmania amazonensis
      parasite infection are chronic, although they are small and self-controlled in
      C57BL/6 mice and severe in BALB/c mice. In the present study we examined the
      presence of hypoxia, HIF-1alpha, HIF-2alpha and VEGF during the course of
      infection in both mouse strains. Hypoxia was detected in lesions from BALB/c mice
      by pimonidazole marking, which occurred earlier than in lesions from C57Bl/6
      mice. The lesions in the BALB/c mice showed HIF-1alpha and HIF-2alpha expression
      in the cytoplasm of macrophages and failed to promote any VEGF expression, while
      lesions in the C57BL/6 mice showed HIF-2alpha nuclear accumulation and subsequent
      VEGF expression. In conclusion, the animal models of leishmaniasis demonstrated a
      diversity of patterns of expression, cell localization and activity of the main
      transducers of hypoxia and may be useful models for studying the pathogenic
      mechanisms of HIF-1alpha and HIF-2alpha during chronic hypoxic diseases.

PMID- 22360824
TI  - Uncommon acquired Gerbode defect following extensive bicuspid aortic valve
      endocarditis.
AB  - Gerbode defect is a rare type of left ventricle to right atrium shunt. It is
      usually congenital in origin, but acquired cases are also described, mainly
      following infective endocarditis, valve replacement, trauma or acute myocardial
      infarction. We report a case of a 50-year-old man who suffered an extensive and
      complex infective endocarditis involving a bicuspid aortic valve, the mitral
      aortic intervalvular fibrosa and the anterior leaflet of the mitral valve. After
      dual valve replacement and annular reconstruction, a shunt between the left
      ventricle and the right atrium--Gerbode defect, and a severe leak of the mitral
      prosthesis were detected. Reintervention was performed with successful shunt
      closure with an autologous pericardial patch and paravalvular leak correction. No
      major complications occurred denying the immediate post-surgery period and the
      follow-up at the first year was uneventful.

PMID- 22360825
TI  - Report on the 3'rd scientific meeting of the "Verein zur Forderung des
      Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in
      Motzen, Germany, Nov. 4'th - Nov. 6'th, 2011.
AB  - From November 4th- 6th 2011, the 3rd NEUROWIND e.V. meeting was held in Motzen,
      Brandenburg, Germany. Like in the previous years, the meeting provided an
      excellent platform for scientific exchange and the presentation of innovative
      projects for young colleagues in the fields of neurovascular research,
      neuroinflammation and neurodegeneration. As kick-off to the scientific sessions,
      Reinhard Hohlfeld, Head of the Institute for Clinical Neuroimmunology in Munich,
      gave an illustrious overview on the many fascinations of neuroimmunologic
      research. A particular highlight on the second day of the meeting was the award
      of the 1'st NEUROWIND e.V. prize for young academics in the field of experimental
      neurology. This award is posted for young colleagues under the age of 35 with a
      significant achievement in the field of neurovascular research, neuroinflammation
      or neurodegeneration and comprises an amount of 20.000 Euro, founded by Merck
      Serono GmbH, Darmstadt. Germany. The first prize was awarded to Ivana Nikic from
      Martin Kerschensteiner's group in Munich for her brilliant work on a reversible
      form of axon damage in experimental autoimmune encephalomyelitis and multiple
      sclerosis, published in Nature Medicine in 2011. This first prize award ceremony
      was a great incentive for the next call for proposals now upcoming in 2012.

PMID- 22360826
TI  - Computational fluid dynamics analysis to determine shear stresses and rates in a
      centrifugal left ventricular assist device.
AB  - Axial flow left ventricular assist devices (LVADs) are a significant improvement
      in mechanical circulatory support. However, patients with these devices
      experience degradation of large von Willebrand factor (vWF) multimers, which is
      associated with bleeding and may be caused by high shear stresses within the
      LVAD. In this study, we used computational fluid mechanics to determine the wall
      shear stresses, shear rates, and residence times in a centrifugal LVAD and assess
      the impact on these variables caused by changing impeller speed and changing from
      a shrouded to a semi-open impeller. In both LVAD types, shear rates were well
      over 10,000/s in several regions. This is high enough to degrade vWF, but it is
      unclear if residence times, which were below 5ms in high-shear regions, are long
      enough to allow vWF cleavage. Additionally, wall shear stresses were below the
      threshold stress of 10Pa only in the outlet tube so it is feasible to
      endothelialize this region to enhance its biocompatibility.

PMID- 22360827
TI  - Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice.
AB  - Proinflammatory cytokines are primary mediators of bone loss in estrogen
      deficiency. This study determined whether alpha-1 antitrypsin (AAT), a
      multifunctional protein with proteinase inhibitor and anti-inflammatory
      activities, mitigates bone loss induced by estrogen deficiency. Mice were either
      sham-operated or ovariectomized and injected with either AAT or phosphate
      buffered saline (PBS). Ovariectomy resulted in decreased wet uterus weight,
      significant bone loss, increased serum leptin concentrations, and higher body
      weight compared to sham. AAT injection increased tibial trabecular bone
      volume/total volume and trabecular thickness compared to PBS injection in
      ovariectomized mice. Ovariectomized mice with AAT treatment had higher uterus
      weight, lower serum osteocalcin levels, fewer bone marrow tartrate-resistant acid
      phosphatase-positive osteoclasts, and less expression of calcitonin receptor in
      bone than that in PBS-injected mice. These data demonstrate that AAT mitigates
      ovariectomy-induced bone loss in mice possibly through inhibiting osteoclast
      activity and bone resorption.

PMID- 22360828
TI  - Switching methadone: a 10-year experience of 345 patients in an acute palliative
      care unit.
AB  - BACKGROUND: The aim of this study was to retrospectively review the chart of
      cancer patients switched to methadone for unfavorable response to the previous
      opioid. METHODS: Retrospective reviewed consecutive medical records of patients
      undergoing opioid switching to methadone were evaluated. Patients who were
      switched from different opioids to methadone, because of poor pain relief in the
      presence of adverse effects limiting further dose increases despite symptomatic
      treatment, were selected. After the initial oral dose, the subsequent doses were
      flexible and were changed timely to fit the patients' needs in an attempt to find
      the best balance between pain and opioid-related symptoms. RESULTS: Three hundred
      forty-five patients underwent switching to methadone. Twenty-seven patients were
      not considered feasible for analysis. Only one patient required the use of
      naloxone for the occurrence of bradypnea. A total of 77.4% substitutions for
      methadone were considered successful. The median time to achieve daily dose
      stabilization in patients successfully switched was 3 days. Fifty-one
      substitutions failed. For all previous opioids, no significant differences
      between initial conversion ratios and ratios achieved after stabilization were
      found (P = 0.42). No significant correlation between the previous opioid dose and
      the final conversion ratio was found (P = 0.19). CONCLUSIONS: Switching to
      methadone from different opioids, using an initial fixed ratio followed by a
      flexible dosing, according to the clinical need, is highly effective and safe
      when performed in an acute pain relief and palliative care unit. Further studies
      should assess this approach in other settings.

PMID- 22360829
TI  - Self-rated health in centenarians: a nation-wide cross-sectional Greek study.
AB  - Self-rated health (SRH) is an inclusive measure of public health that is
      correlated with quality of life and subsequent mortality. Extensive literature
      has identified multiple determinants of SRH in different populations. However,
      such studies on centenarians are scarce and parsimonious. Our objective is to
      identify SRH determinants in centenarians. This is a nationwide cross-sectional
      study on 400 Greek centenarians that was carried out between 2007 and 2010. SRH
      was evaluated by a simple question with a 5-point scale. Three categories of SRH
      were formed (very good/good/poor), which served as the dependent variable in
      multinomial regression models. Various sociodemographic, disease-related,
      lifestyle and psychosocial variables were assessed as candidate determinants of
      SRH. According to our results, SRH ratings among centenarians were better than
      that expected according to previous studies showing worse SRH ratings with
      increasing age in Greece. The 22.4% of the variance in SRH among centenarians was
      predicted by gender, habitat region and status, financial problems, disease
      presence and autonomy. Among lifestyle and psychosocial variables, obesity, good
      relationships with children, lack of feelings of loneliness, high optimism,
      adaptability and an internal health locus of control profile were independently
      associated with good SRH. These results indicate that SRH in individuals of
      extreme longevity were related to specific personal psychosocial factors that
      contribute to healthy aging and thus support the biopsychosocial model of health
      promotion.

PMID- 22360830
TI  - Paid caregiver motivation, work conditions, and falls among senior clients.
AB  - The purpose of this study was to determine the motivation of paid non-familial
      caregivers of seniors, understand more about their work conditions, and identify
      any links to negative outcomes among their senior clients. Ninety-eight paid
      caregivers (eighty-five female and thirteen male), recruited from multiple sites
      (i.e. senior centers, shopping malls, local parks, lobbies of senior apartments,
      caregiver agency meetings) completed face-to-face questionnaires and semi
      structured interviews. We found that 60.7% of participants chose to become a
      caregiver because they enjoyed being with seniors while 31.7% were unable to
      obtain other work, and 8.2% stated it was a prerequisite to a different health
      related occupation. Caregivers stated that the most challenging conditions of
      their work were physical lifting (24.5%), behavioral and psychological symptoms
      of dementia (24.5%), senior depression/mood changes (18.4%), attachment with
      impending death (8.2%), missing injuries to client (5.1%), lack of sleep (4.1%),
      and lack of connection with outside world (3.1%). Caregivers who reported that
      the best part of their job was the salary, flexible hours, and ease of work were
      significantly more likely to have clients who fell and fractured a bone than
      those who enjoyed being with seniors (job characteristics, 62.5% vs. senior
      enjoyment, 25.6%; p<0.004). We concluded that in pursuing their occupation, paid
      caregivers are motivated commonly by their love of seniors and also by their lack
      of other job opportunities. Paid caregivers frequently face challenging work
      conditions. When seeking a caregiver for a senior, motivation of the caregiver
      should be considered when hiring.

PMID- 22360831
TI  - [Update in interleukin-1 inhibition].

PMID- 22360832
TI  - [Management of antiphospholipid syndrome].
AB  - The prevention of thrombosis in the antiphospholipid syndrome (APS) remains
      controversial. The purpose of this review is to provide updated recommendations.
      There is evidence that patients at risk of thrombosis are those with "a pattern
      of high risk antiphospholipid antibodies (aPL)" (presence of a lupus
      anticoagulant [LA], association of several aPL, or persistent aCL at a medium or
      high level), or those with associated systemic lupus erythematosus (SLE). The
      prescription of aspirin in primary prevention is recommended in SLE patients with
      positive LA or persistent aCL at a significant level. Secondary prevention is
      based on a very prolonged anticoagulation. An INR around 2.5 seems to be
      sufficient in patients with venous APS. In case of arterial events, the attitude
      is debated. We propose to maintain a target INR between 3 and 3.5. The possible
      occurrence of relapse despite anticoagulation in the therapeutic target may lead
      to the addition of aspirin. The development of new anti-thrombotic agents might
      change the management of APS in the coming years.

PMID- 22360833
TI  - A novel antioxidant phenanthrenoid dimer from Juncus acutus L.
AB  - A novel phenanthrenoid symmetrical dimer 8,8'-bidehydrojuncusol [1,1',6,6'
      tetramethyl-5,5'-divinyl-8,8'-biphenanthrene-2,2',7,7'-tetraol], a related
      phenanthrenoid monomer, a phenolic chromone, and five flavonoids derivatives have
      been isolated from the halophyte Juncus acutus L., Juncaceae. The structure of
      the dimeric phenanthrenoid was determined on the basis of spectroscopic analyses,
      including 2D NMR spectroscopy, and by spectral correlations. The new dimer and
      the other isolated compounds bearing four phenolic hydroxy groups showed the
      significant in vitro antioxidant activity comparable with that of ascorbic acid
      using 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonate] (ABTS) radical cation
      decolourisation assay. On the basis of the results from an in vitro anti
      inflammatory assay using lipopolysaccharide-stimulated RAW264.7 macrophage cells
      linked with immunoblot analysis, it was found that dimerisation of
      dehydrojuncusol [1,6-dimethyl-5-vinyl-8-phenanthrene-2,7-diol] molecule nearly
      nullified its inhibitory effect on the expression of the pro-inflammatory
      inducible nitric oxide synthase (iNOS) protein.

PMID- 22360834
TI  - Method for characterizing viscoelasticity of human gluteal tissue.
AB  - Characterizing compressive transient large deformation properties of biological
      tissue is becoming increasingly important in impact biomechanics and
      rehabilitation engineering, which includes devices interfacing with the human
      body and virtual surgical guidance simulation. Individual mechanical in vivo
      behaviour, specifically of human gluteal adipose and passive skeletal muscle
      tissue compressed with finite strain, has, however, been sparsely characterised.
      Employing a combined experimental and numerical approach, a method is presented
      to investigate the time-dependent properties of in vivo gluteal adipose and
      passive skeletal muscle tissue. Specifically, displacement-controlled ramp-and
      hold indentation relaxation tests were performed and documented with magnetic
      resonance imaging. A time domain quasi-linear viscoelasticity (QLV) formulation
      with Prony series valid for finite strains was used in conjunction with a
      hyperelastic model formulation for soft tissue constitutive model parameter
      identification and calibration of the relaxation test data. A finite element
      model of the indentation region was employed. Strong non-linear elastic but
      linear viscoelastic tissue material behaviour at finite strains was apparent for
      both adipose and passive skeletal muscle mechanical properties with orthogonal
      skin and transversal muscle fibre loading. Using a force-equilibrium assumption,
      the employed material model was well suited to fit the experimental data and
      derive viscoelastic model parameters by inverse finite element parameter
      estimation. An individual characterisation of in vivo gluteal adipose and muscle
      tissue could thus be established. Initial shear moduli were calculated from the
      long-term parameters for human gluteal skin/fat: G(infinity,S/F)=1850 Pa and for
      cross-fibre gluteal muscle tissue: G(infinity,M)=881 Pa. Instantaneous shear
      moduli were found at the employed ramp speed: G(0,S/F)=1920 Pa and G(0,M)=1032
      Pa.

PMID- 22360835
TI  - Estimation of the forces generated by the thigh muscles for transtibial amputee
      gait.
AB  - The forces generated by the muscles with origin on the human femur play a major
      role in transtibial amputee gait, as they are the most effective of the means
      that the body can use for propulsion. By estimating the forces generated by the
      thigh muscles of transtibial amputees, and comparing them to the forces generated
      by the thigh muscles of normal subjects, it is possible to better estimate the
      energy output needed from prosthetic devices. The purpose of this paper is to
      obtain the forces generated by the thigh muscles of transtibial amputees and
      compare these with forces obtained from the same muscles in the case of normal
      subjects. Two transtibial amputees and four normal subjects similar in size to
      the amputees were investigated. Level ground walking was chosen as the movement
      to be studied, since it is a common activity that most amputees engage in.
      Inverse dynamics and a muscle recruitment algorithm (developed by AnyBody
      Technology((r))) were used for generating the muscle activation patterns and for
      computing the muscle forces. The muscle forces were estimated as two sums: one
      for all posterior muscles and one for the anterior muscles, based on the position
      of the muscles of the thigh relative to the frontal plane of the human body. The
      results showed that a significantly higher force is generated by the posterior
      muscles of the amputees during walking, leading to a general increase of the
      metabolic cost necessary for one step.

PMID- 22360836
TI  - Kawasaki disease in Greek children: a retrospective study.
AB  - BACKGROUND: The studies of series of children with Kawasaki disease (KD) in Greek
      children are limited. OBJECTIVES: To evaluate the epidemiology, clinical
      manifestations, laboratory findings, course and outcome of complete KD in Greek
      children. METHODS: Patients with complete KD who were discharged from our
      hospital and followed up routinely between 2004 and 2011 were included in the
      study. The relevant data were collected using a standardized form. RESULTS: There
      were 49 children (27 boys, 22 girls), mean age: 2.14 years. A seasonal peak of
      the disease during spring and summer months was detected. Changes of the
      extremities and cervical adenopathy were the least commonly met criteria for the
      complete KD diagnosis. The mean time of starting treatment was 6.5 days from the
      disease onset. The majority of patients, 42/49, responded well to a single
      infusion of intravenous immunoglobulin (IVIG), while 7/49 patients who had
      persistent fever despite initial therapy with IVIG needed additional treatment
      with either a second dose of IVIG(5), intravenous pulse of methyl prednisolone(1)
      or infliximab(1). Coronary artery abnormalities were detected
      echocardiographically in 17/49 patients. Most of them (15/17) developed transient
      dilatations which resolved by the 8(th) week of disease onset while only 2
      patients, despite early onset of treatment, developed coronary artery aneurysms
      which required coronary artery bypass grafts at a later stage. CONCLUSIONS: Major
      epidemiologic features of KD detected among Greek children are similar to those
      reported in other populations. This study also demonstrates that significant
      cardiac complications may still occur following the disease even if it is
      diagnosed and treated early.

PMID- 22360837
TI  - Prospective intra-patient evaluation of a shoulder retraction device for
      radiotherapy in head and neck cancer.
AB  - Irradiation of tumors in the larynx and pharynx is often technically challenging
      in patients with a short neck or high shoulders. Shoulder retraction devices can
      sometimes resolve this problem and allow irradiation via lateral beam directions.
      This study aimed to measure the proportion of patients who would benefit from
      such an approach and to quantify the magnitude of the benefit obtained. Twenty
      patients were studied. Simulator images were obtained before and after
      intervention. The additional exposure of the cervical spine was measured. Patient
      comfort and acceptability were assessed with a questionnaire. Improvement of
      exposure of the cervical spine was observed in 80% of patients. In 20%, there was
      either no difference or the position was worse. Shoulder retraction exposed a
      mean of 8.4-10.2 mm more of the cervical spine. Patients in general reported the
      device as comfortable. The use of a shoulder retraction device produced
      clinically significant improvements in exposure of the tissues of the cervical
      spine and neck and should be considered in patients being irradiated for tumors
      arising in the larynx or hypopharynx.

PMID- 22360839
TI  - The mechanics of left ventricular dysfunction in patients with Churg-Strauss
      syndrome.
AB  - BACKGROUND: Heart is frequently involved in Churg-Strauss syndrome (CSS).
      However, the mechanics of left ventricular (LV) dysfunction in CSS has not been
      studied. OBJECTIVE: To assess the mechanics of LV function and to characterize
      the contribution of longitudinal, circumferential and rotational deformation to
      LV dysfunction in CSS. METHODS: We enrolled 22 CSS patients (eight males, mean
      age 43.2 +/- 9.5 years) in remission of their disease and 22 sex- and age-matched
      healthy subjects. All patients underwent conventional and two-dimensional speckle
      tracking echocardiography. Global longitudinal, circumferential and rotational
      deformation parameters were calculated. RESULTS: CSS subjects demonstrated lower
      LV ejection fraction (EF) than controls (56.6 +/- 15.0% vs 63.8 +/- 3.4%; P <
      0.05). When compared to those with LVEF >= 50% (n = 14), CSS patients with LVEF <
      50% (n = 7) had decreased global peak-systolic longitudinal and circumferential
      strain/strain rate (all P < 0.001) and tended to have lower global peak-systolic
      radial strain (P = 0.05). There were no differences between these two subgroups
      in global peak-systolic radial strain rate and LV twist/torsion. When comparing
      individual systolic and diastolic parameters early diastolic longitudinal and
      circumferential strain rate demonstrated the highest correlation with
      corresponding global longitudinal and circumferential peak-systolic strain/strain
      rate (r < -0.80, P < 0.001 for all correlations). CONCLUSIONS: In CSS LV systolic
      dysfunction strongly correlates with longitudinal and circumferential, but not
      radial or rotational systolic components, indicating that impaired LV systolic
      function may result predominantly from impaired contraction of inner and middle,
      but not outer myocardial fiber layers. The spatial correspondence between
      systolic and diastolic deformation parameters suggests the similar impact of
      pathologic process on systolic and diastolic function in CSS.

PMID- 22360840
TI  - Carbon nanotubes induce growth enhancement of tobacco cells.
AB  - Carbon nanotubes have shown promise as regulators of seed germination and plant
      growth. Here, we demonstrate that multiwalled carbon nanotubes (MWCNTs) have the
      ability to enhance the growth of tobacco cell culture (55-64% increase over
      control) in a wide range of concentrations (5-500 MUg/mL). Activated carbon (AC)
      stimulated cell growth (16% increase) only at low concentrations (5 MUg/mL) while
      dramatically inhibited the cellular growth at higher concentrations (100-500
      MUg/mL). We found a correlation between the activation of cells growth exposed to
      MWCNTs and the upregulation of genes involved in cell division/cell wall
      formation and water transport. The expression of the tobacco aquaporin (NtPIP1)
      gene, as well as production of the NtPIP1 protein, significantly increased in
      cells exposed to MWCNTs compared to control cells or those exposed to AC. The
      expression of marker genes for cell division (CycB) and cell wall extension
      (NtLRX1) was also up-regulated in cells exposed to MWCNTs compared to control
      cells or those exposed to activated carbon only.

PMID- 22360841
TI  - Patient-centered care in chronic disease management: a thematic analysis of the
      literature in family medicine.
AB  - OBJECTIVE: The objective was to provide a synthesis of the results of the
      research and discourse lines on main dimensions of patient-centered care in the
      context of chronic disease management in family medicine, building on Stewart et
      al.'s model. METHODS: We developed search strategies for the Medline, Embase, and
      Cochrane databases, from 1980 to April 2009. All articles addressing patient
      centered care in the context of chronic disease management in family medicine
      were included. A thematic analysis was performed using mixed codification, based
      on Stewart's model of patient-centered care. RESULTS: Thirty-two articles were
      included. Six major themes emerged: (1) starting from the patient's situation;
      (2) legitimizing the illness experience; (3) acknowledging the patient's
      expertise; (4) offering realistic hope; (5) developing an ongoing partnership;
      (6) providing advocacy for the patient in the health care system. CONCLUSION: The
      context of chronic disease management brings forward new dimensions of patient
      centered care such as legitimizing the illness experience, acknowledging patient
      expertise, offering hope and providing advocacy. PRACTICE IMPLICATIONS: Chronic
      disease management calls for the adaptation of the family physician's role to
      patients' fluctuating needs. Literature also suggests the involvement of the
      family physician in care transitions as a component of patient-centered care.

PMID- 22360842
TI  - Molecular identification of Anisakis spp. from fishes collected in the Tyrrhenian
      Sea (NW Mediterranean).
AB  - The accurate identification of anisakid nematodes at any life cycle stage is
      important both to deepen the knowledge on their taxonomy, ecology, epidemiology
      and for diagnosis and control, as larval stages cause a clinical disease in
      humans known as anisakidosis. With the aim to investigate the presence of
      anisakid larvae, specimens of horse mackerel, Trachurus trachurus (Linnaeus,
      1758), silver scabbardfish, Lepidopus caudatus (Euphrasen, 1788), European
      anchovy, Engraulis encrasicolus (Linnaeus, 1758) and opah fish, Lampris guttatus
      (Brunnich, 1788), were collected by trawling at depths ranging from 50 to 400 m.
      A molecular approach based on restriction profiles obtained after digestion of
      the nuclear ribosomal ITS region was used to identify Anisakis spp. larvae
      recovered in fish samples. Restriction profiles showed three banding patterns,
      corresponding to Anisakis pegreffii, Anisakis physeteris and to heterozygote
      pattern between A. pegreffii and Anisakis simplex s.s. Specimens showing the
      heterozygote restriction pattern were also analyzed by sequencing of the entire
      ITS region, to confirm the heterozygote status.

PMID- 22360843
TI  - Epidemic protection zones: centred on cases or based on connectivity?
AB  - When an exotic infectious disease invades a susceptible environment, protection
      zones are enforced. Historically, such zones have been shaped as circles of equal
      radius (ER), centred on the location of infected premises. Because the ER policy
      seems to assume that epidemic dissemination is driven by a similar number of
      secondary cases generated per primary case, it does not consider whether local
      features, such as connectivity, influence epidemic dispersal. Here we explored
      the efficacy of ER protection zones. By generating a geographically explicit
      scenario that mimicked an actual epidemic, we created protection zones of
      different geometry, comparing the cost-benefit estimates of ER protection zones
      to a set of alternatives, which considered a pre-existing connecting network (CN)
      - the road network. The hypothesis of similar number of cases per ER circle was
      not substantiated: the number of units at risk per circle differed up to four
      times among ER circles. Findings also showed that even a small area (of <115
      km(2) ) revealed network properties. Because the CN policy required 20% less area
      to be protected than the ER policy, and the CN-based protection zone included a
      23.8% greater density of units at risk/km(2)  than the ER-based alternative,
      findings supported the view that protection zones are likely to be less costly
      and more effective if they consider connecting structures, such as road, railroad
      and/or river networks. The analysis of local geographical factors (contacts,
      vectors and connectivity) may optimize the efficacy of control measures against
      epidemics.

PMID- 22360844
TI  - First-trimester maternal serum vitamin D and mode of delivery.
AB  - Low maternal vitamin D levels have been associated with adverse pregnancy
      outcome. A recent study has suggested that low maternal vitamin D levels at the
      time of delivery are also associated with an almost fourfold increase in
      caesarean section risk. The aim of the present study was to investigate whether
      there is a difference in maternal serum 25-hydroxyvitamin D (25(OH)D) levels at
      11-13 weeks' gestation according to the mode of delivery. Maternal serum 25(OH)D
      levels were measured at 11-13 weeks' gestation in 995 singleton pregnancies
      resulting in the birth of phenotypically normal neonates at term. The measured
      25(OH)D levels were adjusted for maternal age, BMI, racial origin, smoking,
      method of conception and season of blood testing, and the adjusted levels
      (multiple of the median; MoM) were compared between those who subsequently
      delivered vaginally and those that delivered by caesarean section. Delivery was
      vaginal in 79.6 % of cases, by emergency caesarean section in 11.6 % and by
      elective caesarean section in 8.8 %. The median 25(OH)D level in our population
      was 46.82 (interquartile range (IQR) 27.75-70.13) nmol/l. The adjusted maternal
      median 25(OH)D levels in the emergency and elective caesarean section groups
      (0.99, IQR 0.71-1.46 MoM and 0.96, IQR 0.73-1.27 MoM, respectively) were not
      significantly different from the vaginal delivery group (0.99, IQR 0.71-1.33 MoM;
      P = 0.53 and P = 0.81, respectively). First-trimester maternal serum 25(OH)D
      levels are similar between women who subsequently have a vaginal delivery and
      those who deliver by elective or emergency caesarean section.

PMID- 22360845
TI  - Influence of family carers on haemodialyzed patients' adherence to dietary and
      fluid restrictions: an observational study.
AB  - AIM:   To determine the influence of a family carer on haemodialyzed
      patients''adherence'. BACKGROUND:   There is extensive evidence showing that
      successful treatment of patients with end-stage renal disease is directly related
      to patients''adherence'. The parameters indicative of a good adherence are
      potassium and phosphate serum levels and the interdialytic weight gain.
      Haemodialyzed patients may have scarce adherence to food and fluid intake
      restrictions, and medications schedule. DESIGN:   Case-control study carried out
      in a haemodialysis centre in Italy. DATA SOURCES:   The data were collected
      during 2010. METHODS:   A total of 72 subjects with end-stage renal disease
      participated in the study. The subjects assisted by a family carer were
      identified as cases (n = 36), whereas those who did not have a family carer, as
      controls (n = 36). All subjects were followed up (4 months) and checked up
      regarding interdialytic weight gain, and serum levels of potassium and phosphate.
      Important differences in potassium and phosphate serum level and interdialytic
      weight gain between the two groups were evaluated separately using a repeated
      measures anova test. RESULTS:   Participants in the case group showed
      significantly lower phosphate and potassium serum levels and a lower
      interdialytic weight gain during follow-up when compared to controls.
      CONCLUSIONS:   The presence of a family carer improves patients' adherence,
      particularly as far as phosphate levels are concerned, since phosphate intake
      plays a fundamental role in avoiding long-term complications in end-stage renal
      disease patients.

PMID- 22360846
TI  - The effect of vitamin B supplementation on homocysteine metabolism and clinical
      state of patients with chronic epilepsy treated with carbamazepine and valproic
      acid.
AB  - PURPOSE: To investigate the influence of vitamin B supplementation on the plasma
      total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical
      state of patients with chronic epilepsy. METHODS: Beck Depression Inventory (BDI)
      scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year
      of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2).
      RESULTS: Eighty-one patients participated in the study: 51 patients with chronic
      epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30
      patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was
      significantly higher in G1 than G2 (p=0.0001) with no significant differences in
      s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1
      patients (p=0.00002) after 1 year of supplementation and increased in G2 after 1
      year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in
      G1 decreased significantly after 1 year of supplementation (p=0.0001) and
      increased significantly in VPA-treated G2 patients after 1 year of AED therapy
      (p=0.02). The number of hyperhomocysteinemic patients significantly decreased in
      G1 after vitamin B supplementation (p=0.01) and increased in G2 (p=0.002). We
      also observed improved BDI scores and reduced seizure frequency in patients with
      chronic epilepsy. CONCLUSIONS: These data support the hypothesis that AEDs play a
      major role in hyperhomocysteinemia development in patients with epilepsy. Adding
      folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the
      risk of hyperhomocysteinemia.

PMID- 22360847
TI  - Discussing study limitations in reports of biomedical studies- the need for more
      transparency.
AB  - Unbiased and frank discussion of study limitations by authors represents a
      crucial part of the scientific discourse and progress. In today's culture of
      publishing many authors or scientific teams probably balance 'utter honesty' when
      discussing limitations of their research with the risk of being unable to publish
      their work. Currently, too few papers in the medical literature frankly discuss
      how limitations could have affected the study findings and interpretations. The
      goals of this commentary are to review how limitations are currently acknowledged
      in the medical literature, to discuss the implications of limitations in
      biomedical studies, and to make suggestions as to how to openly discuss
      limitations for scientists submitting their papers to journals. This commentary
      was developed through discussion and logical arguments by the authors who are
      doing research in the area of hedging (use of language to express uncertainty)
      and who have extensive experience as authors and editors of biomedical papers. We
      strongly encourage authors to report on all potentially important limitations
      that may have affected the quality and interpretation of the evidence being
      presented. This will not only benefit science but also offers incentives for
      authors: If not all important limitations are acknowledged readers and reviewers
      of scientific articles may perceive that the authors were unaware of them.
      Authors should take advantage of their content knowledge and familiarity with the
      study to prevent misinterpretations of the limitations by reviewers and readers.
      Articles discussing limitations help shape the future research agenda and are
      likely to be cited because they have informed the design and conduct of future
      studies. Instead of perceiving acknowledgment of limitations negatively, authors,
      reviewers and editors should recognize the potential of a frank and unbiased
      discussion of study limitations that should not jeopardize acceptance of
      manuscripts.

PMID- 22360848
TI  - Pulsed radiofrequency treatment for radicular pain: where do we stand and where
      to go?

PMID- 22360849
TI  - Simultaneous determination of L-cysteine and L-tyrosine using Au
      nanoparticles/poly-eriochrome black T film modified glassy carbon electrode.
AB  - A novel Au-nanoparticles/poly-eriochrome black T film modified glassy carbon
      electrode (AuNPs/PEBT/GCE) was constructed for the simultaneous determination of
      l-cysteine (L-Cys) and l-tyrosine (L-Tyr) by differential pulse voltammetry.
      Fourier transform infrared spectra and electrochemical impedance spectroscopy
      indicate that the PEBT film was successfully polymerized on the surface of GCE
      and the film efficiently decreased the charge transfer resistance value of
      electrode and improved the electron transfer kinetic between analytes and
      electrode. The scanning electron microscope image shows that the immobilized
      AuNPs were spherical in shape and enhanced the electrical conductivity of PEBT
      film. In addition, PEBT film increased the oxidation currents of analytes four
      times when compared to bare GCE, and the AuNPs separated the oxidation potentials
      of L-Cys and L-Tyr by 488 mV while bare GCE failed to resolve them. The
      amperometry results exhibit that the electrocatalytic currents increased linearly
      with L-Cys concentrations in the range 0.05-100 MUM (r=0.9981), and the detection
      limits of L-Cys and L-Tyr were 8 nM and 10 nM (S/N=3), respectively. With high
      sensitivity and selectivity, the proposed electrochemical sensor provides a
      simple method for simultaneous determination of L-Cys and L-Tyr.

PMID- 22360850
TI  - A gathering of minds: expanding understanding of the origins of biological
      diversity and the evolution of developmental mechanisms.
AB  - This paper is a short report on the 2012 Society of Integrative and Comparative
      Biology Annual Meeting. Charleston, South Carolina, USA. 3-7 January 2012
      (abstracts freely available at http://www.sicb.org/meetings/2012/).

PMID- 22360851
TI  - Ghrelin modulates testicular germ cells apoptosis and proliferation in adult
      normal rats.
AB  - Under normal condition in the most mammals, spermatogenesis is closely associated
      with the balance between germ cells proliferation and apoptosis. The present
      study was designed to determine the effects of ghrelin treatment on in vivo
      quality and quantity expression of apoptosis and proliferation specific indices
      in rat testicular germ cells. Twenty eight adult normal rats were subdivided into
      equal control and treatment groups. Treatment group received 3 nmol of ghrelin as
      subcutaneous injection for 30 consecutive days or vehicle to the control animals.
      The rats from each group (n=7) were killed on days 10 and 30 and their testes
      were taken for immunocytochemical evaluation and caspase-3 assay.
      Immunohistochemical analysis indicated that the accumulations of Bax and PCNA
      peptides are generally more prominent in spermatocytes and spermatogonia of both
      groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax
      increased (P<0.01) in the ghrelin-treated group on day 10, while despite of 30%
      increment in the Bax level of spermatocytes in the treated rats on day 30,
      however, it was not statistically significant. During the experimental period,
      only a few spermatogonia represented Bax expression and the changes of Bax
      immunolabling cells were negligible upon ghrelin treatment. Likewise, there were
      immunostaining cells against Bcl-2 in each germ cell neither in the control nor
      in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at
      increase of Bax level in the spermatocytes and therefore may stimulate apoptosis
      in these germ cells. In contrast, ghrelin administration significantly suppressed
      proliferation-associated peptide PCNA in the spermatocytes as well as
      spermatogonia (P<0.05). Whereas, caspase-3 activity did not show any marked
      alteration during the experiment in both groups (P>0.05). Upstream of Bax
      substance parallel to down-regulation of PCNA demonstrate that ghrelin may
      prevent massive accumulation of germ cells during normal spermatogenesis. These
      observations also indicate that ghrelin may be considered as a modulator of
      spermatogenesis in normal adult rats and could be potentially implicated for
      abnormal spermatogenesis in some testicular germ cell tumors.

PMID- 22360852
TI  - Triiodothyronine stimulates cystatin C production in bone cells.
AB  - Thyroid hormones increase cystatin C levels in vivo. To study whether 3,3',5
      triiodo-l-thyronine (T(3)) stimulates the production of cystatin C in vitro, we
      used a T(3)-responsive osteoblastic cell line (PyMS) which can be kept in serum
      free culture. We compared the effects of T(3) on cystatin C mRNA expression (by
      Northern) and on protein release (by Western and ELISA) with those of
      dexamethasone (dex). Triiodothyronine increased cystatin C mRNA expression and
      cystatin C accumulation in culture media in a dose- and time-dependent manner,
      1.5-fold at 1 nmol/l after 4d; dex (100 nmol/l) was more potent and increased
      cystatin C accumulation 3-fold after 4d. Triiodothyronine but not dex stimulated
      glucose uptake. Our in vitro findings explain in vivo observations.
      Triiodothyronine-induced increase in the production of cystatin C may be related
      to an increased cell metabolism and proteolysis control demand.

PMID- 22360853
TI  - Seahorses - a source of traditional medicine.
AB  - Wild marine organisms have been used in the discovery and development of
      traditional and allopathic medical treatments for a long time. Seahorses, a
      syngnathidae fish, are one of the important candidate organisms which have been
      used in Chinese traditional medicine from time immemorial. It is believed that
      seahorses have the potential to cure infertility, baldness, asthma and arthritis.
      An authentic research work on the biomedical validation of seahorses proved that
      they have the ability to cure arthritis and its associated inflammation. A
      Cathepsin-derived peptide from the seahorse species of Hippocampus kuda proved to
      be effective in chondrocyte cells and its associated impaired arthritis
      inflammation. Apart from this, seahorses have a putative free radical scavenging
      effect in controlling the ageing process. More authentic research is needed in
      order to validate the biomedical potential. This article highlights the role of
      seahorses' value in traditional medicine and their biomedical properties.

PMID- 22360854
TI  - ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original
      biochemistry and cell biological properties.
AB  - S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone
      selected ABCG2-overexpressing cells and are widely used in in vitro studies of
      multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were
      established to investigate whether the MDR phenotype and cell biological
      properties were maintained in vivo. Our results showed that the proliferation,
      cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in
      cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells).
      Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2
      substrates such as mitoxantrone and topotecan, but remained sensitive to the non
      ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143
      potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results
      suggest that S1-M1-80 cell xenografts in nude mice retain their original
      cytological characteristics at 9 weeks. Thus, this model could serve as a good
      system for further investigation of ABCG2-mediated MDR.

PMID- 22360855
TI  - Expression of miR-125b in the new, highly invasive glioma stem cell and
      progenitor cell line SU3.
AB  - MicroRNA (miR)-125b has been shown to play a potential role in the development of
      glioma stem cells. However, the relationship between miRNA and glioma stem cells
      is still elusive. This study was designed to elucidate this potential
      relationship. We established a highly invasive glioma stem cell and progenitor
      (GSCP) cell line SU3. SU3 cell suspensions were injected into nude mice brains in
      situ, and the invasiveness of graft tumors was analyzed using hematoxylin and
      eosin staining as well as immunohistochemistry. Real-time polymerase chain
      reaction (PCR) was used to measure the expression levels of miR-125b in SU3 and
      other cells. In vitro, SU3 cells expressed CD133 and nestin as well as
      differentiation markers glial fibrillary acidic protein (GFAP) and beta-tubulin
      III, which were consistent with the characteristics of glioma stem cells. Scratch
      assays indicated that the migration ability of SU3 cells was stronger than that
      of U251 stem cells (U251s). In vivo, SU3 cells invaded into each part of the
      mouse brain from the caudate nucleus in a diffuse pattern and highly expressed
      invasive and proliferative cell markers matrix metalloprotease 2 (MMP2), MMP9,
      and Ki-67. Real-time PCR results revealed that the levels of miR-125b and MMP9
      were significantly higher in SU3 and SU2, also a highly invasive GSCP cell line
      we established before, than in U251s. High expression of miR-125b both in newly
      established GSCPs, SU3, and long-term cultured GSCPs, SU2 suggests that miR-125b
      exhibits oncogene-like behavior. This behavior should be considered in further
      studies of miR-125b in cancer stem cells. Furthermore, MMP9, which plays a role
      in cancer stem cell invasion, may be a target gene of miR-125b.

PMID- 22360857
TI  - Relative susceptibility and transcriptional response of nitrogen cycling bacteria
      to quantum dots.
AB  - Little is known about the potential impacts of accidental or incidental releases
      of manufactured nanomaterials to microbial ecosystem services (e.g., nutrient
      cycling). Here, quantum dots (QDs) coated with cationic polyethylenimine (PEI)
      were more toxic to pure cultures of nitrogen-cycling bacteria than QDs coated
      with anionic polymaleic anhydride-alt-1-octadecene (PMAO). Nitrifying bacteria
      (i.e., Nitrosomonas europaea) were much more susceptible than nitrogen fixing
      (i.e., Azotobacter vinelandii, Rhizobium etli, and Azospirillum lipoferum) and
      denitrifying bacteria (i.e., Pseudomonas stutzeri). Antibacterial activity was
      mainly exerted by the QDs rather than by their organic coating or their released
      QD components (e.g., Cd and Zn), which under the near-neutral pH tested (to
      minimize QD weathering) were released into the bacterial growth media at lower
      levels than their minimum inhibitory concentrations. Sublethal exposure to QDs
      stimulated the expression of genes associated with nitrogen cycling. QD-PEI (10
      nM) induced three types of nitrogenase genes (nif, anf, and vnf) in A.
      vinelandii, and one ammonia monooxygenase gene (amoA) in N. europaea was up
      regulated upon exposure to 1 nM QD-PEI. We previously reported up-regulation of
      denitrification genes in P. stutzeri exposed to low concentrations of QD-PEI. (1)
      Whether this surprising stimulation of nitrogen cycling activities reflects the
      need to generate more energy to overcome toxicity (in the case of nitrification
      or denitrification) or to synthesize organic nitrogen to repair or replace
      damaged proteins (in the case of nitrogen fixation) remains to be determined.

PMID- 22360856
TI  - Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern
      China. Deletion of genomic DNA, which occurs during the complex pathogenesis
      process for NPC, represents a pivotal mechanism in the inactivation of tumor
      suppressor genes (TSGs). In many circumstances, loss of TSGs can be detected as
      diagnostic and prognostic markers in cancer. The short arm of chromosome 3 (3p)
      is a frequently deleted chromosomal region in NPC, with 3p21.1-21.2 and 3p25.2
      26.1 being the most frequently deleted minimal regions. In recent years, our
      research group and others have focused on the identification and characterization
      of novel target TSGs at 3p, such as RASSF1A, BLU, RBMS3, and CHL1, in the
      development and progression of NPC. In this review, we summarize recent findings
      of TSGs at 3p and discuss some of these genes in detail. A better understanding
      of TSGs at 3p will significantly improve our understanding of NPC pathogenesis,
      diagnosis, and treatment.

PMID- 22360858
TI  - Reducing expression of GluN1(0XX) subunit splice variants of the NMDA receptor
      interferes with spatial reference memory.
AB  - The GluN1 subunit of the N-methyl-D-aspartate (NMDA) receptor shows age-related
      changes in its expression pattern, some of which correlate with spatial memory
      performance in mice. Aged C57BL/6 mice show an age-related increase in mRNA
      expression of GluN1 subunit splice variants that lack the N terminal splice
      cassette, GluN1(0XX) (GluN1-a). This increase in expression is associated with
      good performance in reference and working memory tasks. The present study was
      undertaken to determine if GluN1(0XX) splice variants are required for good
      performance in reference memory tasks in young mice. Mice were bilaterally
      injected with either siRNA specific for GluN1(0XX) splice variants, control siRNA
      or vehicle alone into ventro-lateral orbital cortices. A fourth group of mice did
      not receive any injections. Starting five days post-injection, mice were tested
      for their performance in spatial reference memory, associative memory and
      cognitive flexibility tasks over four days in the Morris water maze. There was a
      10-19% reduction in mRNA expression for GluN1(0XX) splice variants within the
      ventro-lateral orbital cortices in mice following GluN1(0XX) siRNA treatment.
      Declines in performance within the first half of reference memory testing were
      seen in the mice receiving siRNA against the GluN1(0XX) splice variants, as
      compared to the mice injected with control siRNA, vehicle and/or no treatment.
      These results suggest a role for the GluN1(0XX) splice variants in orbital
      regions for early acquisition and/or consolidation of spatial reference memory.

PMID- 22360859
TI  - Sp1 is involved in regulation of cystathionine gamma-lyase gene expression and
      biological function by PI3K/Akt pathway in human hepatocellular carcinoma cell
      lines.
AB  - Hydrogen sulfide (H(2)S) has been found to play an important role as a novel
      gasotransmitter involved in many biological processes. The regulatory role of
      endogenous H(2)S-producing enzyme on cancer cell survival is complex and unclear.
      According to the data that cystathionine gamma-lyase (CSE) gene, catalyzed H(2)S
      production in trans-sulfuration pathway, was upregulated in Akt stably
      transformed mouse embryonic fibroblast cells, the mechanisms that elevated CSE
      expression by PI3K/Akt signaling pathway and its biological functions in cell
      survival were studied. In the present study, firstly, the results showed that
      PI3K/Akt positively correlated with CSE expression levels in human hepatocellular
      carcinoma cell lines. CSE expression was decreased by the PI3K inhibitor or Akt
      deletion, while upregulated with the activating of Akt. Based on dual-luciferase
      reporter assay, the -592/+139 gene fragment represented the CSE core promoter,
      and the PI3K/Akt pathway regulated CSE expression on transcriptional level. Sp1
      was the critical transcription factor in regulation of CSE expression via the
      mutation of transcription factor binding sites on the promoter. Furthermore, we
      proved that Sp1 could directly bind to CSE promoter by ChIP assay. In addition,
      we explored that the endogenous H(2)S production was connected with the regulated
      CSE expression, and CSE/H(2)S promoted human hepatocellular carcinoma cell
      proliferation via cell cycle progression regulation. In summary, we have, for the
      first time, demonstrated that PI3K/Akt pathway regulates the CSE expression via
      Sp1, which is particularly important to understand the effect of PI3K/Akt and CSE
      on the tumorigenesis.

PMID- 22360860
TI  - Intra- and interobserver reproducibility of left ventricular mechanical
      dyssynchrony assessment by real time three-dimensional echocardiography.
AB  - BACKGROUND: Real time three-dimensional (3D) echocardiography allows the
      assessment of left ventricular (LV) mechanical dyssynchrony and may be useful in
      predicting response to cardiac resynchronization therapy. However,
      reproducibility of 3D dyssynchrony in past reports varied widely. We evaluated
      intra- and interobserver reproducibility of parameters of LV mechanical
      dyssynchrony by 3D echocardiography and explored the impact of image quality as a
      possible source of variability. METHODS: LV volumes and ejection fraction (LV EF)
      were measured by 3D echocardiography in 90 subjects. LV mechanical dyssynchrony
      was calculated as the standard deviation of the time-to-minimum segmental volume
      (Tmsv) over 16 (SDI16) and 12 (SDI12) segments and as the maximum time-difference
      in Tmsv over 16 (Dif16), 12 (Dif12), and 2 (DifS-L) segments. Opposing wall delay
      in peak myocardial systolic velocity (S-L delay) by tissue Doppler imaging (TDI)
      was also evaluated. RESULTS: Feasibility of 3D measurements was 88.9%. Intra- and
      interobserver intraclass correlation coefficients were excellent for LV volumes,
      LV EF, and S-L delay (all >= 0.90), very good for SDI16 (0.83 and 0.85), moderate
      to good for SDI12, Dif16, Dif12, and DifS-L (0.51-0.81). No systematic bias was
      present between readings for 3D dyssynchrony, but limits of agreement resulted
      fairly large for most parameters with the exception of SDI16, which showed
      reproducibility slightly lower than TDI. Suboptimal image quality was a
      significant source of variability in 3D-dyssynchrony assessment. CONCLUSIONS: The
      3D assessment of LV volumes and dyssynchrony was feasible in our community-based
      cohort. SDI16 was the most reproducible among 3D-dyssynchrony parameters and the
      least affected by image quality.

PMID- 22360861
TI  - Interdisciplinary approach to the demography of Jamaica.
AB  - BACKGROUND: The trans-Atlantic slave trade dramatically changed the demographic
      makeup of the New World, with varying regions of the African coast exploited
      differently over roughly a 400 year period. When compared to the discrete
      mitochondrial haplotype distribution of historically appropriate source
      populations, the unique distribution within a specific source population can
      prove insightful in estimating the contribution of each population. Here, we
      analyzed the first hypervariable region of mitochondrial DNA in a sample from the
      Caribbean island of Jamaica and compared it to aggregated populations in Africa
      divided according to historiographically defined segments of the continent's
      coastline. The results from these admixture procedures were then compared to the
      wealth of historic knowledge surrounding the disembarkation of Africans on the
      island. RESULTS: In line with previous findings, the matriline of Jamaica is
      almost entirely of West African descent. Results from the admixture analyses
      suggest modern Jamaicans share a closer affinity with groups from the Gold Coast
      and Bight of Benin despite high mortality, low fecundity, and waning regional
      importation. The slaves from the Bight of Biafra and West-central Africa were
      imported in great numbers; however, the results suggest a deficit in expected
      maternal contribution from those regions. CONCLUSIONS: When considering the
      demographic pressures imposed by chattel slavery on Jamaica during the slave era,
      the results seem incongruous. Ethnolinguistic and ethnographic evidence, however,
      may explain the apparent non-random levels of genetic perseverance. The
      application of genetics may prove useful in answering difficult demographic
      questions left by historically voiceless groups.

PMID- 22360862
TI  - Wholegrain oat-based cereals have prebiotic potential and low glycaemic index.
AB  - Population studies show a positive association between increased dietary intake
      of wholegrains and reduced risk of cardiometabolic disorders. Consumption of
      wholegrain food has been associated with lower blood glucose and therefore may
      contribute to a low-glycaemic load diet. The ability to mediate a prebiotic
      modulation of gut microbiota has recently been suggested to have an inverse
      correlation with risk of cardiometabolic disease. To date very little work has
      been carried out on the functionality of wholegrain breakfast cereals in terms of
      glycaemic response or impact on gut microbiota. An investigation into identifying
      wholegrain-based breakfast cereals demonstrating both low glycaemic index (GI)
      and prebiotic attributes was performed. After in vitro digestion, cereal samples
      were supplemented to pH-controlled anaerobic batch cultures of the human faecal
      microbiota. Total bacteria populations increased significantly (P < 0.05) in all
      treated cultures, and the fermentation of a wholegrain oat cluster cereal was
      associated with proliferation of the Bifidobacterium genus (P = 0.02). Smaller,
      but significant increases in the Bifidobacterium genus were observed for a
      further four oat-based cereals. Significant increases in the Lactobacillus
      Enterococcus group were observed for granola (P = 0.01), 100 % wholegrain
      aggregate (P = 0.04) and 70 % wholegrain loops (P = 0.01). Cereals demonstrating
      prebiotic potential were selected for GI determination in twelve healthy
      subjects. The wholegrain oat aggregate cereal achieved the lowest GI value (40),
      three other cereals ranged between 44 and 74, with instant porridge resulting in
      a GI value similar to the standard glucose control. The present study suggests
      that wholegrain oat-based breakfast cereals may be prebiotics and have the
      potential to have low GI.

PMID- 22360863
TI  - Malignant paraganglioma of the mesentery: a case report and review of literature.
AB  - Paragangliomas represent only 10% of chromaffin tissue tumors and those arising
      from the mesentery seem to be a rare occurrence. We report a case of a 55 year
      old man in whom an abdominal mass was discovered fortuitously by ultrasonography
      during a routine health exam. He presented occasional heart palpitations and
      diaphoresis as well as a well-demarcated mass upon abdominal physical
      examination. CT scan revealed a solid polylobulated mass in the right lower
      quadrant. Exploration laparotomy revealed a voluminous multi-nodular tumoral
      mass, which contained hemorrhagic spots. Histopathological studies confirmed the
      presence of a paraganglioma. The excision of the mass as well as the surrounding
      intestine and mesentery also revealed two lymphatic metastases, the first among
      14 documented cases to be described concerning mesenteric paragangliomas. One
      year follow up and CT scan revealed neither recurrence nor the presence of
      distant metastases.

PMID- 22360864
TI  - How old is cancer?

PMID- 22360865
TI  - Review of reported complications associated with the Pipeline Embolization
      Device.

PMID- 22360866
TI  - Echoes from the anatomic theatre of Padua: Casserius and Fabricius antagonism.

PMID- 22360867
TI  - Population-based data: the impact on glioma treatment for elderly patients.

PMID- 22360868
TI  - Aberrations of chromosomes 9 and 22 in acute lymphoblastic leukemia cases
      detected by ES-fluorescence in situ hybridization.
AB  - A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL
      fusion in the breakpoint region of the derivative chromosome 22. The aim of this
      study was to evaluate the importance of atypical fluorescence in situ
      hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic
      leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL
      (294 tests), including 139 childhood and 69 adult cases by FISH technique using
      BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL
      cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m
      BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of
      both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene
      amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies
      of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL
      cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell
      clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of
      Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy
      9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and
      coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and
      polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns
      for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However,
      monosomy 9 and ABL gene amplification were highly specific for childhood T cell
      acute lymphoblastic leukemia (T-ALL) patients. Our report presents the
      correlation between atypical FISH signal patterns and clinical findings of a
      large group of ALL cases.

PMID- 22360869
TI  - Detection of oligoclonal IgG kappa and IgG lambda bands in cerebrospinal fluid
      and serum with HevyliteTM antibodies. comparison with the free light chain
      oligoclonal pattern.
AB  - BACKGROUND: Oligoclonal IgG bands in cerebrospinal fluid that are absent in serum
      indicate intrathecal IgG synthesis and are a sensitive marker of CNS inflammatory
      diseases, in particular multiple sclerosis. It may be of interest to determine
      whether these bands are predominantly IgGkappa or IgGlambda. METHODS: We have
      used HevyliteTM antibodies and developed a technique for detection of oligoclonal
      IgGkappa and IgGlambda bands by means of isoelectric focusing followed by
      immunoblotting. The same technique was used for oligoclonal free kappa and free
      lambda detection. Among several techniques tested, affinity immunoblotting
      appears to be the most sensitive; it can detect less than 1 ng of IgGkappa or
      IgGlambda paraprotein. We compared oligoclonal IgG profiles with those of
      oligoclonal IgGkappa and IgGlambda. There was good agreement concerning the
      presence or absence of intrathecal synthesis. We observed the ratios between
      oligoclonal IgGkappa and IgGlambda bands, and they did not always match the
      ratios between free kappa and free lambda bands. We were also able to detect
      antigen-specific CSF-restricted oligoclonal IgGkappa and IgGlambda bands in
      neuroborreliosis. It remains to be determined subsequently by a clinically
      oriented prospective study, whether predominant IgGkappa/IgGlambda or free
      kappa/free lambda can be observed more frequently in particular diseases with
      oligoclonal IgG synthesis. DISCUSSION: Very sensitive detection of oligoclonal
      IgGkappa and IgGlambda bands in cerebrospinal fluid with Hevylite antibodies is
      feasible; detection of antigen-specific IgGkappa or IgGlambda is possible as
      well. In particular situations, e.g. when difficulties arise in distinguishing
      between oligoclonal and monoclonal pattern, the test may be of considerable
      clinical value.

PMID- 22360870
TI  - Number and sex ratio of children and impact of parental diabetes in individuals
      with Type 1 diabetes.
AB  - OBJECTIVE: To assess the number and sex ratio of children in individuals with
      Type 1 diabetes mellitus and the influence of parental diabetes on age at onset
      of Type 1 diabetes in our cohort. METHODS: In a cross-sectional study in a German
      region comprising 350,000 inhabitants, 697 subjects with Type 1 diabetes (364
      women, 333 men) underwent a standardized assessment regarding the number and sex
      of their children and the family history of diabetes. RESULTS: Compared with 1.36
      children per woman in the German background population, the total fertility rate
      in the calendar year of 2010 in our female cohort with Type 1 diabetes (age 18-49
      years) was 0.88. Men with Type 1 diabetes had a fertility rate of 0.65. More men
      (51.1%) than women (35.7%; P < 0.0001) were childless. Twenty per cent of all
      women aged 41-45 years in the background population were childless compared with
      36.2% of all women and 52% of all men in this specific age group from our cohort.
      The sex ratio of female vs. male offspring of individuals with Type 1 diabetes
      did not differ significantly from the expected 1:1 ratio. Maternal Type 1 or Type
      2 diabetes increased the age at onset of Type 1 diabetes from 22.9 +/- 13.7 (no
      maternal diabetes) to 28.6 +/- 16.8 and 30.1 +/- 15.1 years (p < 0.0001),
      respectively. CONCLUSIONS: Compared with the German reference population,
      individuals with Type 1 diabetes had significantly fewer children and were more
      often childless. The sex ratio female vs. male offspring of women and men with
      Type 1 diabetes was unaffected. Maternal history of Type 1 and Type 2 diabetes
      was associated with a significant later onset of Type 1 diabetes.

PMID- 22360871
TI  - Epilepsy care and mental health care for people with epilepsy: California Health
      Interview Survey, 2005.
AB  - INTRODUCTION: Epilepsy, which requires complex care, can be further complicated
      by comorbid mental illness. Evidence indicates deficiencies exist in the care
      received for both epilepsy-related care and for mental health care in people with
      epilepsy. Evidence indicates there are deficiencies in both these areas for
      people with epilepsy. Our objective was to evaluate treatment gaps in epilepsy
      and mental health care among California adults with epilepsy and to compare the
      mental health services and treatment received by people with epilepsy to that of
      the general population. METHODS: We conducted multivariate analyses of data from
      the 2005 California Health Interview Survey (N = 43,020), which included data
      from 604 adult participants who said they had been told they had epilepsy, to
      examine comparisons of interest. RESULTS: Twenty-seven percent of California
      adults with epilepsy who had had at least 1 seizure in the past 3 months had not
      seen a neurologist or epilepsy specialist in the past year. Of respondents with
      psychological distress and epilepsy, 84% perceived a need for mental health care
      in the past year, but only 57% had seen a mental health provider during that
      time. Of respondents without epilepsy but with psychological distress, 77%
      perceived a need for mental health care in the past year, but only 32% had seen a
      mental health provider during that time. CONCLUSION: California adults with
      epilepsy appear to have substantial unmet needs in both epilepsy care and mental
      health care. Adults with epilepsy and psychological distress appeared to have
      received more mental health treatment than psychologically distressed adults
      without epilepsy. Efforts should be made to improve access to quality epilepsy
      care that includes assessment and treatment of mental health disorders.

PMID- 22360873
TI  - Evaluation of a telephone-based physical activity promotion program for
      disadvantaged older adults.
AB  - BACKGROUND: Lack of adequate physical activity among older adults has been widely
      documented. Although interventions aimed at increasing physical activity that are
      based on behavioral strategies and theories have been shown to increase activity
      levels among older adults, little is known about responses to these interventions
      in different population segments. COMMUNITY CONTEXT: The Physical Activity for a
      Lifetime of Success (PALS) program attempted to translate a telephone-based,
      motivational support program for physical activity, Active Choices, for use by a
      low-income, ethnically diverse population of older adults living in southeast
      Seattle. This article describes the evaluation of PALS at the end of the 5-year
      program. METHODS: Evaluation data included a data set of participant physical
      activity assessments; internal study documents; and interviews with key PALS
      stakeholders, participants, volunteers, and people eligible for PALS who declined
      to enroll when invited. OUTCOME: PALS demonstrated improved physical activity
      levels among the sedentary older adults who participated in the program, but the
      PALS model did not appeal widely to a diverse, low-income target population.
      Extensive recruitment efforts resulted in a low number of participants, and
      attempts to recruit peer volunteers were largely unsuccessful. INTERPRETATION:
      Considering the resources required to engage both participants and volunteers,
      PALS does not appear to be a sustainable model for delivering support for
      physical activity to community-dwelling minority and low-income older adults.

PMID- 22360872
TI  - The food environment and student weight status, Los Angeles County, 2008-2009.
AB  - INTRODUCTION: One factor believed to affect overweight status is the food
      environment, or the distribution of outlets that serve healthful or unhealthful
      foods in residential areas, workplaces, and schools. Few studies have
      investigated the association between the food environment and the prevalence of
      overweight among children and adolescents. The objective of this study was to
      investigate the association between the distribution of corner stores and fast
      food restaurants around Los Angeles County public schools and the prevalence of
      overweight among students. METHODS: Hierarchical linear models were used to
      assess the association between the presence of corner stores or fast food
      restaurants within a half-mile of Los Angeles County schools (N = 1,694) and
      overweight prevalence among students in grades 5, 7, and 9. RESULTS: The presence
      of corner stores and fast food restaurants varied significantly by schools'
      racial/ethnic composition, Title 1 eligibility, and rural/suburban vs urban
      location. After adjustment for other factors, overweight prevalence was 1.6
      percentage points higher at majority-Latino schools that had at least 1 corner
      store within a half-mile than at majority-Latino schools that did not have a
      corner store within a half-mile. The association between corner stores and
      overweight prevalence varied significantly between majority-Latino schools and
      schools that were majority-white or that had no racial/ethnic majority. The
      presence of fast food restaurants within a half-mile of schools was not
      associated with overweight prevalence among students. CONCLUSION: This study
      underscores the importance of interventions that seek to improve the
      healthfulness of corner store inventories and of student purchases.

PMID- 22360874
TI  - Calculating reach of evidence-based weight loss and memory improvement
      interventions among older adults attending Arkansas senior centers, 2008-2011.
AB  - INTRODUCTION: Older adults could benefit from public health interventions that
      address the health conditions they face. However, translation of evidence-based
      interventions into the community has been slow. We implemented 2 evidence-based
      interventions delivered by lay health educators in Arkansas senior centers from
      2008 to 2011: a behavioral weight loss intervention and a memory improvement
      intervention. The objective of this study was to measure the ability of these
      programs to reach and serve the growing population of older Americans. We report
      on differences in program enrollment by age, sex, race, and ethnicity and suggest
      how our approach to calculating the reach of the 2 interventions can guide future
      research and program development. METHODS: We defined the reach of the 2
      interventions as the proportion of people who needed the intervention and
      responded to initial recruitment efforts but who did not enroll compared with the
      proportion of people who needed the intervention and actually enrolled in the
      program. To calculate these proportions, we used Reach, Efficacy/Effectiveness,
      Adoption, Implementation, and Maintenance framework formulas. We defined need as
      the prevalence of obesity (body mass index in kg/m2 >=30) and the level of
      concern about memory problems among older adults aged 60 years or older. Our
      target population was 2,198 people aged 60 years or older who attend 15 senior
      centers in Arkansas. RESULTS: More than half of our target population responded
      to recruitment efforts for the behavioral weight loss intervention (61.9%) and
      for the memory improvement intervention (58.1%), yielding an overall response
      rate of 59.7%. More than one-third (35.6%) of the target population enrolled in
      the behavioral weight loss intervention, and 22.8% enrolled in the memory
      improvement intervention, for an overall reach for the 2 programs of 27.9%.
      CONCLUSION: The reach of 2 evidence-based interventions designed for older adults
      that targeted specific health conditions and that were delivered in senior
      centers by community members was high. Our approach to calculating reach in
      applied settings can guide future research and program development.

PMID- 22360875
TI  - ParentChecker: a computer program for automated inference of missing parental
      genotype calls and linkage phase correction.
AB  - BACKGROUND: Accurate genetic maps are the cornerstones of genetic discovery, but
      their construction can be hampered by missing parental genotype information.
      Inference of parental haplotypes and correction of phase errors can be done
      manually on a one by one basis with the aide of current software tools, but this
      is tedious and time consuming for the high marker density datasets currently
      being generated for many crop species. Tools that help automate the process of
      inferring parental genotypes can greatly speed the process of map building. We
      developed a software tool that infers and outputs missing parental genotype
      information based on observed patterns of segregation in mapping populations.
      When phases are correctly inferred, they can be fed back to the mapping software
      to quickly improve marker order and placement on genetic maps. RESULTS:
      ParentChecker is a user-friendly tool that uses the segregation patterns of
      progeny to infer missing genotype information of parental lines that have been
      used to construct a mapping population. It can also be used to automate
      correction of linkage phase errors in genotypic data that are in ABH format.
      CONCLUSION: ParentChecker efficiently improves genetic mapping datasets for cases
      where parental information is incomplete by automating the process of inferring
      missing genotypes of inbred mapping populations and can also be used to correct
      linkage phase errors in ABH formatted datasets.

PMID- 22360876
TI  - Developing and delivering clinical pharmacology in the UK National Health
      Service.
AB  - Clinical pharmacologists are active in the delivery of general and specialist
      medical services across the UK. They also make major contributions, both locally
      and nationally, to medicines management and appraisal in the National Health
      Service. Most are also heavily involved in the organization and delivery of
      teaching and training of a range of healthcare professionals, both undergraduates
      and postgraduates. In the past, these contributions may not have been fully
      recognized, perhaps in part because the discipline is small. However, the British
      Pharmacological Society, particularly through its Clinical Section, is committed
      to initiatives to ensure that all clinical pharmacologists (whatever their
      background, training or subsequent working environment) can work together to
      improve patient care, nationally and internationally. Effective engagement with
      universities, the National Health Service and pharmaceutical companies will be
      vital if these initiatives are to have sustained benefits and improve health
      outcomes for patients.

PMID- 22360877
TI  - Random mating and reproductive compatibility among Argentinean and southern
      Brazilian populations of Anastrepha fraterculus (Diptera: Tephritidae).
AB  - As a prerequisite for area-wide application of the sterile insect technique in an
      area encompassing northern Argentina and southern Brazil, prezygotic and
      postzygotic reproductive compatibility among three geographically distant
      populations in the area was tested. In field cages, sexually mature adults of
      each population were found to be sexually compatible, mating duration was not
      affected by fly origin and there was no clear evidence of spatial partition of
      mating location. In the laboratory, homotypic and heterotypic crosses for all
      possible combinations displayed similar levels of fertility and yielded F1 adults
      without distortion of the sex ratio. Finally, F1 hybrid and parental adults
      produced equally viable F2 eggs. Put together, our results and those from earlier
      studies suggest that a large area, ranging from Buenos Aires to the surroundings
      of Sao Paulo, could be managed using a single A. fraterculus mass-reared strain.
      At the northern margin of this area, two A. fraterculus morphotypes appear to
      coexist in sympatry. We delineate future research to further delimit the
      distribution of the aff1 morphotype (Argentina-southern Brazil) and to gain
      insight into evolutionary patterns producing divergence and radiation of tropical
      fruit fly species. 

PMID- 22360879
TI  - Dabigatran efficacy-safety assessment for stroke prevention in patients with
      atrial fibrillation.

PMID- 22360878
TI  - Down-regulation of the transcription factor snail in the placentas of patients
      with preeclampsia and in a rat model of preeclampsia.
AB  - BACKGROUND: Placental malfunction in preeclampsia is believed to be a consequence
      of aberrant differentiation of trophoblast lineages and changes in utero
      placental oxygenation. The transcription factor Snail, a master regulator
      molecule of epithelial-mesenchymal transition in embryonic development and in
      cancer, is shown to be involved in trophoblast differentiation as well. Moreover,
      Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined
      the expression of Snail and its downstream target, e-cadherin, in human normal
      term, preterm and preeclamptic placentas, and in pregnant rats that developed
      preeclampsia-like symptoms in the response to a 20-fold increase in sodium
      intake. METHODS: Western blotting analysis was used for comparative expression of
      Snail and e- cadherin in total protein extracts. Placental cells expressing Snail
      and e-cadherin were identified by immunohistochemical double-labeling technique.
      RESULTS: The levels of Snail protein were decreased in human preeclamptic
      placentas by 30% (p < 0.01) compared to normal term, and in the rat model by 40%
      (p < 0.001) compared to control placentas. In preterm placentas, the levels of
      Snail expression varied, yet there was a strong trend toward statistical
      significance between preterm and preeclamptic placentas. In humans, e-cadherin
      protein level was 30% higher in preeclamptic (p < 0.05) placentas and similarly,
      but not significantly (p = 0.1), high in the preterm placentas compared to normal
      term. In the rat model of preeclampsia, e-cadherin was increased by 60% (p <
      0.01). Immunohistochemical examination of human placentas demonstrated Snail
      positive staining in the nuclei of the villous trophoblasts and mesenchymal cells
      and in the invasive trophoblasts of the decidua. In the rat placenta, the
      majority of Snail positive cells were spongiotrophoblasts of the junctional zone,
      while in the labyrinth, Snail-positive sinusoidal giant trophoblasts cells were
      found in some focal areas located close to the junctional zone. CONCLUSION: We
      demonstrated that human preeclampsia and the salt-induced rat model of
      preeclampsia are associated with the reduced levels of Snail protein in placenta.
      Down-regulation of the transcription factor Snail in placental progenitor cell
      lineages, either by intrinsic defects and/or by extrinsic and maternal factors,
      may affect normal placenta development and function and thus contribute to the
      pathology of preeclampsia.

PMID- 22360880
TI  - Dementia early diagnosis: triggers, supports and constraints affecting the
      decision to engage with the health care system.
AB  - OBJECTIVES: There is very often a lengthy delay between first noticing symptoms
      of dementia and making first contact with Health Care Professionals (HCPs). This
      article identifies influences on the decision to contact HCPs for the first time.
      METHOD: Qualitative thematic analysis of 20 case studies of carer experience.
      Participants were carers of people who attended Memory Clinic services. RESULTS:
      Key themes emerging were: triggers, supports and constraints. The analysis draws
      out the social nature of the decision to engage with the health care system,
      considering the negotiations that occur and the areas that are contested.
      CONCLUSIONS: Constraints generate delays at several points during the journey
      from first noticing something may be amiss to making first contact with an HCP.
      Supports and Triggers legitimise carer's actions to contact HCPs for the first
      time.

PMID- 22360881
TI  - How does BAFF activate B cells in patients with autoimmune diseases?

PMID- 22360883
TI  - The dual probiotic and antibiotic nature of Bdellovibrio bacteriovorus.
AB  - Bdellovibrio bacteriovorus is a predatory bacterium which attacks and consumes
      other bacterial strains, including the well known pathogens E. coli O157 : H7,
      Salmonella typhimurium and Helicobacter pylori. This remarkable activity has been
      the focus of research for nearly five decades, with exciting practical
      applications to medical, agriculture and farming practices recently being
      published. This article reviews many of the exciting steps research into this
      bacterium, and similar bacteria, has taken, focusing primarily on their use as
      both an antibiotic to remove harmful and pathogenic bacteria and as a probiotic
      to help curb and control the bacterial populations within the intestinal tract.
      Owing to the unique and dual nature of this bacterium, this review proposes the
      use of "amphibiotic" to describe these bacteria and their activities.

PMID- 22360882
TI  - Rewiring carbon catabolite repression for microbial cell factory.
AB  - Carbon catabolite repression (CCR) is a key regulatory system found in most
      microorganisms that ensures preferential utilization of energy-efficient carbon
      sources. CCR helps microorganisms obtain a proper balance between their metabolic
      capacity and the maximum sugar uptake capability. It also constrains the
      deregulated utilization of a preferred cognate substrate, enabling microorganisms
      to survive and dominate in natural environments. On the other side of the same
      coin lies the tenacious bottleneck in microbial production of bioproducts that
      employs a combination of carbon sources in varied proportion, such as
      lignocellulose-derived sugar mixtures. Preferential sugar uptake combined with
      the transcriptional and/or enzymatic exclusion of less preferred sugars turns out
      one of the major barriers in increasing the yield and productivity of
      fermentation process. Accumulation of the unused substrate also complicates the
      downstream processes used to extract the desired product. To overcome this
      difficulty and to develop tailor-made strains for specific metabolic engineering
      goals, quantitative and systemic understanding of the molecular interaction map
      behind CCR is a prerequisite. Here we comparatively review the universal and
      strain-specific features of CCR circuitry and discuss the recent efforts in
      developing synthetic cell factories devoid of CCR particularly for lignocellulose
      based biorefinery.

PMID- 22360884
TI  - RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction.
AB  - In asthma, T helper 2 (T(H)2)-type cytokines such as interleukin (IL)-4, IL-5,
      and IL-13 are produced by activated CD4(+) T cells. Dendritic cells played an
      important role in determining the fate of naive T cells into either T(H)1 or
      T(H)2 cells. We determined whether RG-II regulates the T(H)1/T(H)2 immune
      response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4
      production but increased interferon- gamma production, and inhibited GATA-3 gene
      expression. RG-II also inhibited asthmatic reactions including an increase in the
      number of eosinophils in bronchoalveolar lavage fluid, an increase in
      inflammatory cell infiltration in lung tissues, airway luminal narrowing, and
      airway hyperresponsiveness. This study provides evidence that RG-II plays a
      critical role in ameliorating the pathogenic process of asthmatic inflammation in
      mice. These findings provide new insights into the immunotherapeutic role of RG
      II in terms of its effects in a murine model of asthma.

PMID- 22360885
TI  - CopA3 peptide from Copris tripartitus induces apoptosis in human leukemia cells
      via a caspase-independent pathway.
AB  - Our previous study demonstrated that CopA3, a disulfide dimer of the coprisin
      peptide analogue (LLCIALRKK), has antibacterial activity. In this study, we
      assessed whether CopA3 caused cellular toxicity in various mammalian cell lines.
      CopA3 selectively caused a marked decrease in cell viability in Jurkat T, U937,
      and AML-2 cells (human leukemia cells), but was not cytotoxic to Caki or Hela
      cells. Fragmentation of DNA, a marker of apoptosis, was also confirmed in the
      leukemia cell lines, but not in the other cells. CopA3-induced apoptosis in
      leukemia cells was mediated by apoptosis inducing factor (AIF), indicating
      induction of a caspase-independent signaling pathway.

PMID- 22360886
TI  - Purification and characterization of a thermostable glutamate dehydrogenase from
      a thermophilic bacterium isolated from a sterilization drying oven.
AB  - Glutamate dehydrogenase from axenic bacterial cultures of a new microorganism,
      called GWE1, isolated from the interior of a sterilization drying oven, was
      purified by anion-exchange and molecular-exclusion liquid chromatography. The
      apparent molecular mass of the native enzyme was 250.5 kDa and was shown to be an
      hexamer with similar subunits of molecular mass 40.5 kDa. For glutamate
      oxidation, the enzyme showed an optimal pH and temperature of 8.0 and 70 degrees
      C, respectively. In contrast to other glutamate dehydrogenases isolated from
      bacteria, the enzyme isolated in this study can use both NAD(+) and NADP(+) as
      electron acceptors, displaying more affinity for NADP(+) than for NAD(+). No
      activity was detected with NADH or NADPH, 2-oxoglutarate and ammonia. The enzyme
      was exceptionally thermostable, maintaining more than 70% of activity after
      incubating at 100(o)C for more than five hours suggesting being one of the most
      thermoestable enzymes reported in the family of dehydrogenases.

PMID- 22360887
TI  - Isolation and characterization of three maize aquaporin genes, ZmNIP2;1, ZmNIP2;4
      and ZmTIP4;4 involved in urea transport.
AB  - Urea-based nitrogen fertilizer was widely utilized in maize production, but
      transporters involved in urea uptake, translocation and cellular homeostasis have
      not been identified. Here, we isolated three maize aquapoin genes, ZmNIP2;1,
      ZmNIP2;4 and ZmTIP4;4, from a cDNA library by heterogeneous complementation of a
      urea uptake-defective yeast. ZmNIP2;1 and ZmNIP2;4 belonged to the nodulin 26
      like intrinsic proteins (NIPs) localized at plasma membrane, and ZmTIP4;4
      belonged to the tonoplast intrinsic protein (TIPs) at vacuolar membrane.
      Quantitative RT-PCR revealed that ZmNIP2;1 was expressed constitutively in
      various organs while ZmNIP2;4 and ZmTIP4;4 transcripts were abundant in
      reproductive organs and roots. Expression of ZmTIP4;4 was significantly increased
      in roots and expanded leaves under nitrogen starvation, while those of ZmNIP2;1
      and ZmNIP2;4 remained unaffected. Functions of maize aquapoin genes in urea
      transport together with their distinct expression manners suggested that they
      might play diverse roles on urea uptake and translocation, or equilibrating urea
      concentration across tonoplast.

PMID- 22360888
TI  - Functional study of Villin 2 protein expressed in longissimus dorsi muscle of
      Korean native cattle in different growth stages.
AB  - The aim of this study was to investigate protein profiles related to the
      induction of adipogenesis within the bovine longissimus dorsi muscle (BLDM) by
      proteomic analysis. We analyzed BLDM proteins at different growth stages to
      clarify the physiological mechanisms of marbled muscle development in 20 head of
      Korean native cattle (11 month: 10 head, 17 month: 10 head). BLDM proteins were
      analyzed by two-dimensional electrophoresis and image analysis. Villin 2 was
      specifically identified by mass spectrometry and a protein search engine. Villin
      2 protein expression in BLDM decreased during the fat development stage in test
      steers. In a Western blot cell culture study of spontaneously immortal bovine
      muscle fibroblasts, the abundance of Villin 2 was shown to be down-regulated
      during differentiation into muscle. In 3T3-L1 mouse embryonic fibroblasts, Villin
      2 was decreased during differentiation into adipocytes. The results suggest that
      Villin 2 may be related to the induction of transdifferentiation and adipogenesis
      in bovine longissimus dorsi muscle.

PMID- 22360889
TI  - Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated
      murine macrophages.
AB  - Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In
      this study, we investigated whether protopine derived from Hypecoum erectum L
      could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine
      macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO),
      cyclooxygenase-2 (COX-2), and prostaglandin E(2) (PGE(2)) production by LPS
      stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw
      264.7 cells with protopine reduced the production of pro-inflammatory cytokines.
      These inhibitory effects were caused by blocking phosphorylation of mitogen
      activated protein kinases (MAP kinases) and also blocking activation of a nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB).

PMID- 22360890
TI  - Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative
      modification of neurofilament-L protection by histidyl dipeptides.
AB  - Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound
      derived from dopamine metabolism and is capable of causing dopaminergic
      neurodegeneration. Oxidative modification of neurofilament proteins has been
      implicated in the pathogenesis of neurodegenerative disorders. In this study,
      oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory
      effects of histidyl dipeptides on NF-L modification were investigated. When NF-L
      was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in
      a time-dependent manner. We also found that the generation of hydroxyl radicals
      (*OH) was linear with respect to the concentrations of salsolinol as a function
      of incubation time. NF-L exposure to salsolinol produced losses of glutamate,
      lysine and proline residues. These results suggest that the aggregation of NF-L
      by salsolinol may be due to oxidative damage resulting from free radicals.
      Carnosine, histidyl dipeptide, is involved in many cellular defense processes,
      including free radical detoxification. Carnosine, and anserine were shown to
      significantly prevent salsolinol- mediated NF-L aggregation. Both compounds also
      inhibited the generation of *OH induced by salsolinol. The results indicated that
      carnosine and related compounds may prevent salsolinol-mediated NF-L modification
      via free radical scavenging.

PMID- 22360891
TI  - GoBean: a Java GUI application for visual exploration of GO term enrichments.
AB  - We have developed a biologist-friendly, Java GUI application (GoBean) for GO term
      enrichment analysis. It was designed to be a comprehensive and flexible GUI tool
      for GO term enrichment analysis, combining the merits of other programs and
      incorporating extensive graphic exploration of enrichment results. An intuitive
      user interface with multiple panels allows for extensive visual scrutiny of
      analysis results. The program includes many essential and useful features, such
      as enrichment analysis algorithms, multiple test correction methods, and
      versatile filtering of enriched GO terms for more focused analyses. A unique
      graphic interface reflecting the GO tree structure was devised to facilitate
      comparisons of multiple GO analysis results, which can provide valuable insights
      for biological interpretation. Additional features to enhance user convenience
      include built in ID conversion, evidence code-based gene-GO association
      filtering, set operations of gene lists and enriched GO terms, and user -provided
      data files. It is available at http://neon.gachon.ac.kr/GoBean/.

PMID- 22360892
TI  - Cloning and characterization of polyA- RNA transcripts encoded by activated B1
      like retrotransposons in mouse erythroleukemia MEL cells exposed to methylation
      inhibitors.
AB  - We have previously identified a DNA silent region located downstream of the 3'
      end of the beta(major) globin gene (designated B1-559) that contains a B1
      retrotransposon, consensus binding sites for erythroid specific transcription
      factors and shares the capacity to act as promoter in hematopoietic cells
      interacting with beta-globin gene LCR sequences in vitro. In this study, we have
      cloned four new non-polyA RNA transcripts being detected upon blockade of murine
      erythroleukemia (MEL) cell differentiation to erythroid maturation by methylation
      inhibitors and demonstrated that two of them share high structural homology with
      sequences of B1 element found within the B1-559 region. Although it is not clear
      yet whether and how these RNAs interfere with induction of erythroid maturation,
      these data provide evidence for the first time showing that methylation
      inhibitors can activate silent repetitive DNA sequences in MEL cells and may have
      implications in cancer chemotherapy using demethylating drugs as antineoplastic
      agents.

PMID- 22360893
TI  - How should training of graduates in clinical pharmacology and therapeutics be
      delivered and assessed?
AB  - The UK postgraduate curriculum in clinical pharmacology and therapeutics (CPT)
      incorporates the common competencies required of all physicians and shows how
      trainees from other specialties, including primary care, can train in CPT.
      Various models of training and assessment are possible. Evolution of the current
      system to meet new challenges would maintain an established tradition, with a
      ready source of training funds. However, this would require greater input from
      all consultants in CPT, including the training and assessment of trainees. A
      joint venture with the Faculty of Pharmaceutical Medicine would have the
      advantage, if the Faculty agreed, of introducing ready-made curriculum modules
      and assessment tools that have been accepted by the General Medical Council.
      However, extra modules relevant to CPT would have to be constructed to complement
      the common areas already in the pharmaceutical medicine curriculum, and there
      would be a perceived loss of the independence that clinical pharmacologists
      currently enjoy when making decisions about manufacturers' products. Abandoning
      externally approved training in CPT would allow the specialty to devise its own
      training and assessment in the necessary skills. Critically, however, this would
      impair the status of the specialty and would incur loss of financial support from
      postgraduate Deaneries. To attract high-calibre trainees, we must completely
      define CPT training and assessment structures. Most clinical pharmacologists seem
      to prefer to allow the current structures to evolve under external guidance.
      However, this will not succeed unless all trained clinical pharmacologists
      contribute to development of both the curriculum and specific assessment tools,
      and open their teaching and assessment skills to scrutiny.

PMID- 22360894
TI  - Mitochondrial basis of the anti-arrhythmic action of lidocaine and modulation by
      the n-6 to n-3 PUFA ratio of cardiac phospholipids.
AB  - The aim of this study was to evaluate the involvement of mitochondria in the
      mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing
      either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular
      mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused
      according to the working mode using a medium with or without lidocaine 5 MUm.
      They were then subjected to local ischemia (20 min) and reperfusion (30 min).
      Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of
      cardiac phospholipids. Reperfusing the ischemic area favored the incidence of
      severe arrhythmias. Lidocaine treatment abolished almost completely reperfusion
      arrhythmias in the FO group, but did not display anti-arrhythmic properties in
      the SSO group. As it was indicated by measurements of the mitochondrial function,
      lidocaine seemed to favor mitochondrial calcium retention in the FO group, which
      might prevent cytosolic calcium spikes and reperfusion arrhythmias. In the SSO
      group, the resistance to lidocaine was associated with an aggravation of cellular
      damages. The mitochondrial calcium retention capacities were saturated, and
      lidocaine was unable to increase them, making the drug inefficient in preventing
      reperfusion arrhythmias. 

PMID- 22360895
TI  - Antiadhesive activity of the biosurfactant pseudofactin II secreted by the Arctic
      bacterium Pseudomonas fluorescens BD5.
AB  - BACKGROUND: Pseudofactin II is a recently identified biosurfactant secreted by
      Pseudomonas fluorescens BD5, the strain obtained from freshwater from the Arctic
      Archipelago of Svalbard. Pseudofactin II is a novel compound identified as cyclic
      lipopeptide with a palmitic acid connected to the terminal amino group of eighth
      amino acid in peptide moiety. The C-terminal carboxylic group of the last amino
      acid forms a lactone with the hydroxyl of Thr3. Adhesion is the first stage of
      biofilm formation and the best moment for the action of antiadhesive and anti
      biofilm compounds. Adsorption of biosurfactants to a surface e.g. glass,
      polystyrene, silicone modifies its hydrophobicity, interfering with the microbial
      adhesion and desorption processes. In this study the role and applications of
      pseudofactin II as a antiadhesive compound has been investigated from medicinal
      and therapeutic perspectives. RESULTS: Pseudofactin II lowered the adhesion to
      three types of surfaces (glass, polystyrene and silicone) of bacterial strains of
      five species: Escherichia coli, Enterococcus faecalis, Enterococcus hirae,
      Staphylococcus epidermidis, Proteus mirabilis and two Candida albicans strains.
      Pretreatment of a polystyrene surface with 0.5 mg/ml pseudofactin II inhibited
      bacterial adhesion by 36-90% and that of C. albicans by 92-99%. The same
      concentration of pseudofactin II dislodged 26-70% of preexisting biofilms grown
      on previously untreated surfaces. Pseudofactin II also caused a marked inhibition
      of the initial adhesion of E. faecalis, E. coli, E. hirae and C. albicans strains
      to silicone urethral catheters. The highest concentration tested (0.5 mg/ml)
      caused a total growth inhibition of S. epidermidis, partial (18-37%) inhibition
      of other bacteria and 8-9% inhibition of C. albicans growth. CONCLUSION:
      Pseudofactin II showed antiadhesive activity against several pathogenic
      microorganisms which are potential biofilm formers on catheters, implants and
      internal prostheses. Up to 99% prevention could be achieved by 0.5 mg/ml
      pseudofactin II. In addition, pseudofactin II dispersed preformed biofilms.
      Pseudofactin II can be used as a disinfectant or surface coating agent against
      microbial colonization of different surfaces, e.g. implants or urethral
      catheters.

PMID- 22360896
TI  - Mode of inheritance of increased host acceptance in a seed beetle.
AB  - Colonization of a novel plant by herbivorous insects is frequently accompanied by
      genetic changes that progressively improve larval or adult performance on the new
      host. This study examined the genetic basis of adaptation to a marginal host
      (lentil) by the seed beetle Callosobruchus maculatus (F.). Quasi-natural
      selection in the laboratory rapidly increased the tendency to oviposit on lentil.
      The mode of inheritance of this increase in host acceptance was determined from
      crosses between three lentil-adapted lines and a line maintained on the ancestral
      host, mung bean. In each set of crosses, females from the lentil lines laid two
      to three times more eggs on lentil than did females from the mung-bean line.
      Hybrid females consistently displayed an intermediate level of host acceptance,
      which did not differ between reciprocal crosses. Alleles promoting greater
      oviposition on lentil thus were inherited additively, with no evidence of sex
      linkage or cytoplasmic effects. In a time-course study, hybrid females initially
      resembled the parent from the mung-bean line, as few eggs were laid on lentil
      during the first 24 h. However, oviposition rates on lentil after 72 h were
      closer to the rate observed in the lentil-line parent. Inferences about
      additivity vs. dominance in genes affecting oviposition may, therefore, depend on
      experimental protocol. Comparison with earlier work suggests that inheritance
      patterns observed in crosses between recently derived selection lines (as in this
      study) may differ from those obtained in crosses between long-divergent
      geographic populations. 

PMID- 22360897
TI  - Left atrial appendage aneurysm with paroxysmal atrial fibrillation.
AB  - Aneurysm of the left atrial appendage is extremely rare, and afflicted patients
      most commonly present with atrial tachyarrhythmia or thromboembolism. For these
      patients, resection of the aneurysm is the recommended and preferred therapy. We
      present the case of a 57-year-old woman who was found incidentally to have a
      large aneurysm of the left atrial appendage presenting as atrial fibrillation.
      After surgical intervention with resection of the aneurysm and a Cox maze III
      procedure, the patient recovered and was discharged in sinus rhythm.

PMID- 22360898
TI  - Noninvasive evaluation of coronary artery bypass grafts with 16-slice
      multidetector computed tomography.
AB  - BACKGROUND: The aim of this study was to investigate the diagnostic accuracy of
      16-slice multislice, multidetector computed tomography (MDCT) angiography for the
      evaluation of grafts in patients with coronary artery bypass grafting (CABG).
      METHODS: Fifty-eight consecutive patients with CABG who underwent both MDCT and
      conventional invasive coronary angiography were included. The median time
      interval between the 2 procedures was 10 days (range, 1-32 days). The
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of MDCT for the detection of occluded grafts were
      calculated. The accuracy of MDCT angiography for detecting significant stenoses
      in patent grafts and the evaluability of proximal and distal anastomoses were
      also investigated. RESULTS: Optimal diagnostic images could not be obtained for
      only 3 (2%) of 153 grafts. Evaluation of the remaining 150 grafts revealed values
      for sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the MDCT
      angiography procedure for the diagnosis of occluded grafts of 87%, 97%, 94%, 93%,
      and 92%, respectively. All of the proximal anastomoses were optimally visualized.
      In 4 (8%) of 50 patent arterial grafts, however, the distal anastomotic region
      could not be evaluated because of motion and surgical-clip artifacts. The
      accuracy of MDCT angiography for the detection of significant stenotic lesions
      was relatively low (the sensitivity, specificity, PPV, and NPV were 67%, 98%,
      50%, and 99%, respectively). The number of significant lesions was insufficient
      to reach a reliable conclusion, however. CONCLUSION: Our study showed that MDCT
      angiography with 16-slice systems has acceptable diagnostic performance for the
      evaluation of coronary artery bypass graft patency.

PMID- 22360899
TI  - Midterm outcomes of simultaneous hybrid coronary artery revascularization for
      left main coronary artery disease.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility, safety,
      and midterm outcomes of a simultaneous hybrid revascularization strategy for left
      main coronary artery disease (LMCAD), compared with conventional off-pump
      coronary artery bypass grafting (OPCAB). METHODS: We compared the in-hospital and
      midterm outcomes of a simultaneous hybrid revascularization strategy (minimally
      invasive direct coronary bypass grafting of the left anterior descending coronary
      artery [LAD] and percutaneous intervention to non-LAD lesions) in 20 patients
      with LMCAD in an enhanced operating room. These patients were matched by
      propensity score to a group of 20 control patients who underwent standard OPCAB
      between September 2007 and December 2009. RESULTS: All baseline clinical
      characteristics of the 2 groups were similar. All of the patients in the 2 groups
      underwent surgery uneventfully without conversion to on-pump coronary artery
      bypass grafting. Compared with OPCAB, the patients in the hybrid group had
      shorter lengths of stay in the intensive care unit (34.8 +/- 37.6 hours versus
      50.7 +/- 34.5 hours, P = .01). Transfusion requirements were reduced in the
      hybrid patients compared with the OPCAB patients (5% versus 40%, P = .01). The 2
      groups did not differ with respect to the occurrence of other important
      morbidities. During the mean (+/-SD) follow-up of 18.5 +/- 9.8 months, the group
      of patients who underwent the simultaneous hybrid procedure experienced an
      incidence of major adverse cardiac or cerebrovascular events that was similar to
      that of the OPCAB control group (100% versus 90%, respectively; P = .31).
      CONCLUSIONS: The midterm follow-up indicated that the simultaneous hybrid
      revascularization procedure for LMCAD is feasible, safe, and effective. These
      promising early findings warrant further prospective investigations.

PMID- 22360900
TI  - Midterm results of axilloaxillary cardiopulmonary bypass.
AB  - BACKGROUND: Total axilloaxillary cardiopulmonary bypass (CPB) is an alternative
      peripheral cannulation technique that has the advantages of antegrade flow during
      CPB, monohemispherical brain perfusion in case of circulatory arrest, and
      achieving excellent decompression of the heart during sternotomy. The results of
      this strategy, particularly beyond the immediately postoperative period, are not
      well known. METHODS: Eleven patients with huge aortic aneurysms (>80 mm) and/or
      acute-subacute ascending aorta dissections underwent surgery with totally
      axilloaxillary CPB. Short- and midterm outcomes, including survival and
      complications relating to axilloaxillary cannulation, were reported. RESULTS: All
      attempts at axillary artery cannulation were successful. Ten of the 11 axillary
      vein cannulation attempts were successful, and the target pump flow was achieved
      via the axillary vein alone. Postoperatively, clinical examinations revealed no
      cases of arm ischemia or compartment syndrome. Three patients (27.3%) experienced
      ipsilateral brachial plexus neuropathy that produced right hand weakness. The
      neuropathy was transient in 2 patients, and the symptoms resolved completely.
      Hospital death occurred in 1 (9.1%) of the 11 patients. The mean (+/-SD) follow
      up time was 956 +/- 292 days. One of the survivors died on postoperative day 105
      from subacute graft infection and sepsis. The right arms of all 9 of the living
      patients were examined physically and by Doppler ultrasonography. We found a
      chronic recanalized thrombotic change in the subclavian vein in 1 patient
      (11.1%), who had no complaints. CONCLUSIONS: Axilloaxillary CPB is an alternative
      technique that can be used under certain conditions. Adding axillary venous
      cannulation to axillary artery cannulation at least does not increase the risk of
      a procedure that uses the axillary artery alone, either in the early or mid term.

PMID- 22360901
TI  - Efficacy of cut-and-sew box isolation of the posterior left atrium for treatment
      of atrial fibrillation-long-term follow-up after a modified maze procedure.
AB  - BACKGROUND: Box isolation of the posterior left atrium is one surgical or
      catheter ablative approach for treating atrial fibrillation (AF). In such cases,
      incomplete transmurality or recovery of pulmonary vein conduction after the
      application of various ablative techniques is considered the main reason for the
      recurrence of postprocedural arrhythmia. The use of solely cut-and-sew box
      isolation does not have these disadvantages and therefore demonstrates maximum
      efficacy for this therapeutic approach. METHODS: We treated 15 patients with both
      an indication for open heart surgery and AF (2 paroxysmal, 6 short persistent
      [<12 months], and 7 long persistent [>12 months] cases) with a solely cut-and-sew
      box lesion. These patients were then retrospectively followed up over the long
      term with respect to the end point of freedom of atrial tachyarrhythmias >30
      seconds. RESULTS: The median follow-up duration was 42 months (range, 32-84
      months). Five (63%) of 8 patients with preoperative paroxysmal or short
      persistent AF had no arrhythmia recurrence, whereas arrhythmia recurrence was
      documented in all 7 patients with preoperative long persistent AF. CONCLUSIONS:
      Despite reliable transmural isolation with cut-and-sew lesions, we observed long
      term arrhythmia recurrence in patients who had preoperative paroxysmal or short
      persistent AF, suggesting that therapy approaches that are more complex than box
      isolation might be needed for selected patients to achieve long-term stable sinus
      rhythm, despite the initially paroxysmal or short persistent character of the
      arrhythmia. A high rate of recurrence in patients with severe structural heart
      disease and preoperative long persistent AF might indicate that, in general,
      isolation of the left posterior atrium alone is not an adequate therapeutic
      approach for these patients.

PMID- 22360902
TI  - Endovascular approach to treat aortic pseudoaneurysms: could it be a safe
      alternative?
AB  - Aortic pseudoaneurysm is a rare complication after blunt chest trauma or cardiac
      surgical procedures and can occur at the site of cannulation or root vent
      insertion on the ascending aorta. These pseudoaneurysms have the potential to
      expand, erode, and rupture, and detecting this condition before complications
      occur is the key to successful management. We had replaced the mitral valve with
      a 31-mm bioprosthesis in an 82-year-old patient and repaired an ascending aorta
      aneurysm, but a computed tomography scan on postoperative day 18 revealed a
      pseudoaneurysm at the site of the previous aortic cannulation. Because of the
      patient's advanced age and multiple comorbidities, we sealed off the neck of the
      pseudoaneurysm with a 12-mm Amplatzer Vascular Plug in the interventional
      cardiology suite instead of subjecting her to a surgical repair involving redo
      sternotomy and a period of circulatory arrest. Deployment of the Amplatzer plug
      effectively shut off flow into the pseudoaneurysm, and the patient recovered
      well. Although the optimal management strategy for aortic pseudoaneurysms is a
      matter of controversy, endovascular interventions may be a safer alternative to
      surgery for patients with multiple comorbidities.

PMID- 22360903
TI  - Staged procedures versus primary repair for tetralogy of Fallot and small left
      ventricle.
AB  - INTRODUCTION: This study was conducted to address whether staged surgical
      intervention or primary repair would be preferred for treating patients with
      tetralogy of Fallot and small left ventricle. METHODS: We retrospectively
      assessed 28 patients with tetralogy of Fallot and small left ventricle at the
      Chinese PLA 208th Hospital, Changchun, between January 2005 and December 2008. Of
      this cohort, 11 patients had undergone a systemic-to-pulmonary arterial shunt
      with a polytetrafluoroethylene interposition graft (off pump), followed by
      ancillary repair procedures as a surgically staged group; the remaining 17
      patients underwent primary intracardiac repair via cardiopulmonary bypass. The
      oxygen level as measured by pulse oximetry (SpO2), the McGoon ratio, and the left
      ventricular end-diastolic volume index (LVEDVI) were measured before shunt
      procedures and at 6 to 18 months afterwards. All data were analyzed statistically
      with the paired Student t test. The 2 groups were compared with respect to LVEDVI
      values and McGoon indices at baseline by the independent t test. RESULTS: None of
      the patients died as a direct result of the surgery, but 1 fatality due to
      pneumonia occurred 4 months after shunting. Mean postshunt values for SpO2, the
      McGoon ratio, and the LVEDVI increased significantly from 76.8% +/- 9.0% to 87.5%
      +/- 2.4% (P < .01), from 1.42 +/- 0.27 to 1.62 +/- 0.32 (P < .05), and from 20.1
      +/- 7.0 mL/m2 to 34.3 +/- 7.4 mL/m2 (P < .01), respectively. Nine patients were
      fully repaired within the 6- to 18-month time frame after shunting, while 1
      patient awaited definitive surgery for pulmonary hypoplasia. In the primary
      repair group, in which the increases the LVEDVI and McGoon ratio were
      comparatively higher, 1 patient died of hypoxemia. CONCLUSION: A LVEDVI 20 mL/m2
      may be an indication for primary repair in patients with tetralogy of Fallot.
      With values <20 mL/m2, staged procedures (i.e., shunt with a
      polytetrafluoroethylene interposition graft) can promote left ventricle
      development and allow safe transition to the final repair.

PMID- 22360904
TI  - Transapical versus conventional aortic valve replacement--a propensity-matched
      comparison.
AB  - INTRODUCTION: The goal of this study was to compare the short- and long-term
      outcomes after aortic valve (AV) surgery carried out via standard
      sternotomy/partial sternotomy versus transapical transcatheter AV implantation
      (taTAVI). PATIENTS AND METHODS: All 336 patients who underwent taTAVI between
      2006 and 2010 were compared with 4533 patients who underwent conventional AV
      replacement (AVR) operations between 2001 and 2010. Using propensity score
      matching, we identified and consecutively compared 2 very similar groups of 167
      patients each. The focus was on periprocedural complications and long-term
      survival. RESULTS: The 30-day mortality rate was 10.8% and 8.4% (P = .56) for the
      conventional AVR patients and the TAVI patients, respectively. The percentages of
      postoperative pacemaker implantations (15.0% versus 6.0%, P = .017) and cases of
      renal failure requiring dialysis (25.7% versus 12.6%, P = .004) were higher in
      the TAVI group. Kaplan-Meier curves diverged after half a year in favor of
      conventional surgery. The estimated 3-year survival rates were 53.5% +/- 5.7%
      (TAVI) and 66.7% +/- 0.2% (conventional AVR). CONCLUSION: Our study shows that
      even with all the latest successes in catheter-based AV implantation, the
      conventional surgical approach is still a very good treatment option with
      excellent long-term results, even for older, high-risk patients.

PMID- 22360906
TI  - Thoracic compartment syndrome: a case report.
AB  - Thoracic compartment syndrome has been observed after trauma and after
      mediastinal and cardiac procedures; however, an adult respiratory distress
      syndrome (ARDS)-like presentation has not been described as a part of thoracic
      compartment syndrome. We describe the case of an obese patient who underwent
      coronary artery bypass (his third such procedure) and hiatal hernia reduction
      during the same operation, followed by transmyocardial laser revascularization
      and full chest closure the next day. The patient was hypoxic after chest closure.
      Two days later, his peak airway pressure increased, and his cardiac and urine
      outputs decreased. Chest radiography findings suggested ARDS without hemodynamic
      instability. After we reopened the sternal incisions, the patient's symptoms
      reversed. Although our patient initially appeared to have ARDS, we believe the
      organ-volume displacement that occurred during the lengthy dual operation
      produced a thoracic and abdominal compartment syndrome that responded to
      decompression of the chest.

PMID- 22360905
TI  - Efficiency of antibacterial suture material in cardiac surgery: a double-blind
      randomized prospective study.
AB  - OBJECTIVE: Postoperative surgical site infections (SSI) still greatly affect
      mortality and morbidity in cardiovascular surgery. SSI may be related to the
      suture material. In this prospective, randomized, controlled, and double-blinded
      study, the effect of antibacterial suture material on SSI in cardiac surgical
      patients was investigated. METHODS: We randomly allocated 510 patients into 2
      groups. Antibacterial suture materials were used for wound closure in 170
      patients (triclosan-coated suture group), and routine suture materials were used
      in 340 patients (noncoated suture group). All patients were evaluated for SSI on
      days 10, 20, and 30 following cardiac surgery. RESULTS: Preoperative risk factors
      and laboratory findings were comparable for the 2 groups. Sternal infection
      occurred in 4 (2.4%) of the patients in the triclosan-coated suture group and in
      3.5% of the noncoated suture group (P > .05). Leg wound infection occurred in 5
      (3.5%) of the patients in the triclosan-coated suture group and in 3.8% of the
      noncoated suture group (P > .05). Only diabetes mellitus was an independent
      predictor of SSI. CONCLUSION: Both noncoated and triclosan-coated suture
      materials are safe. Larger studies may be needed to show the benefit and cost
      effectiveness, if any, of triclosan-coated materials over noncoated materials.

PMID- 22360907
TI  - Epicardial cysts: report of two rare cases.
AB  - Epicardial cysts originating directly from the epicardium are seen very rarely.
      Complete surgical excision is recommended when these cysts are detected. If cysts
      compress surrounding vital structures, cardiopulmonary bypass (CPB) should also
      be considered. We report herein 2 cases of multiloculated epicardial cysts, both
      of which were successfully excised, 1 with CPB.

PMID- 22360908
TI  - Hybrid coronary revascularization for the treatment of left main coronary artery
      disease in high-risk patients.
AB  - OBJECTIVE: Hybrid coronary revascularization is an alternative for treatment for
      high-risk patients with coronary artery disease. We evaluated the efficacy of
      staged hybrid coronary revascularization for the treatment of unprotected left
      main coronary artery disease in high-risk patients. METHODS: Patients with left
      main or proximal left anterior descending coronary artery stenosis who are not
      good candidates for percutaneous coronary intervention and who had suitable
      lesions in the right coronary and circumflex arteries were considered for staged
      hybrid therapy if they had poor left ventricular functions (ejection fraction
      <0.40) and comorbid illnesses. From January 2008 through December 2010, 11
      patients (8 men, 3 women; mean age: 66.1 +/- 9.1 years) were treated with off
      pump coronary artery bypass grafting combined with staged percutaneous coronary
      intervention. Nine patients had left main coronary artery stenosis together with
      circumflex or right coronary artery stenosis, and 2 patients had proximal left
      anterior descending artery stenosis and right coronary artery stenosis. RESULTS:
      After off-pump coronary artery bypass grafting, procedure-related complications
      did not occur, and there was no in-hospital death. Coronary re-angiography after
      a median of 16 days revealed patent and functioning left internal mammarian
      artery grafts in all patients. Applying subsequent percutaneous transluminal
      coronary angioplasty and occasional stenting (n = 14), a total of 14 lesions were
      treated successfully. Procedure related complications did not occur. All patients
      remained angina-free, and no stress electrocardiographic changes were recorded.
      CONCLUSION: Our preliminary results indicate that a "staged hybrid" approach to
      the treatment of left main coronary artery disease in high-risk patients is safe
      and effective. Hybrid coronary revascularization enables complete
      revascularization and may be an alternative method of treating left main coronary
      artery disease in selected high-risk patients.

PMID- 22360909
TI  - Shortness of breath: pulmonary embolism, ischemic heart failure, or both? The
      role of concomitant surgery.
AB  - We present a case of a patient who underwent successful concomitant surgical
      management of his massive pulmonary embolism and severe multivessel coronary
      disease. His presentation with shortness of breath prompted a comprehensive
      evaluation, which revealed both problems. This experience emphasizes the
      importance of considering both problems, because treating one but not the other
      could be catastrophic.

PMID- 22360910
TI  - Tricuspid valve papillary fibroelastoma: a rare tumor with a diagnostic dilemma.
AB  - Papillary fibroelastoma is a rare primary tumor of the heart valves. This lesion
      can occur on any of the valves or endothelial surface of the heart and has been
      detected by echocardiography, by cardiac catheterization, during open heart
      operations for other conditions, and at autopsy. Because of the potential for
      comorbidities, this tumor should be removed. We present the case of an elderly
      man with a diagnosis of severe mitral valve regurgitation and moderate tricuspid
      valve regurgitation who was suspected to have a tricuspid valve vegetation.
      Mitral valve replacement, tricuspid valve repair, and excision of the lesion were
      performed successfully. A histologic examination of the vegetation confirmed it
      to be a papillary fibroelastoma. We present this case to emphasize the rarity of
      this tumor and the importance of a correct diagnosis to avoid delaying its prompt
      and definitive management.

PMID- 22360911
TI  - Episodic circulatory collapse caused by intermittent prosthetic aortic valve
      dysfunction.
AB  - An 80-year-old woman with a 20-mm Medtronic Hall (tilting-disc) aortic prosthesis
      presented with episodes of chest pain associated with circulatory collapse and
      subsequent rapid spontaneous recovery. A computed tomography angiogram
      demonstrated no evidence of aortic dissection, pulmonary embolus, or coronary
      artery disease. A transthoracic echocardiogram demonstrated a well-functioning
      prosthetic aortic valve. After another inpatient episode, auscultation
      demonstrated an intermittent absence of the prosthetic second heart sound. A
      transesophageal echocardiography examination revealed that the aortic valve was
      intermittently sticking in the open position. During the emergency replacement,
      the existing valve was noted to have pannus and overlying thrombus, which are
      rare in this type of valve but can lead to dramatic circulatory collapse when
      present. This case demonstrates how a diagnosis of intermittent valve dysfunction
      can prove elusive. It is important, as part of the assessment of mechanical
      valves, to perform regular, careful auscultation and echocardiographic
      examination, with emphasis on recording in Doppler or M-mode through the valve at
      slow sweep speeds for a prolonged period in order to maximize the chance of
      diagnosing episodic valve dysfunction.

PMID- 22360912
TI  - Nursing students' willingness to blow the whistle.
AB  - BACKGROUND AND PURPOSE: Whistleblowing in the nursing profession is a complex
      dilemma. If nurses decide to do nothing to stop a colleague's or management's
      harmful conduct, they may be violating their basic professional commitment to
      promote and protect patients' health. Whistleblowing is also complex given that
      the act might have negative consequences for the whistleblower as well as the
      wrong doer. This study aims to answer three questions, and suggests some lines
      for further research on this topic as well as ways for integrating it in the
      nursing curriculum: Are nursing students willing to take action to stop
      misconduct in order to protect a patient's interest? Are they willing to report
      the misconduct to authorities within an organization and/or outside of it? Are
      they willing to report a colleague's wrongdoing as well as that of a manager?
      SUBJECT AND METHODS: Eighty two nursing students in Israel were presented with a
      questionnaire containing two vignettes, and required to make a decision that
      involved whistleblowing. One vignette described a case of misconduct of a
      colleague, and the other a misconduct of a manager. RESULTS: The findings
      indicate that the students considered acts that are detrimental to the patient to
      be very serious. The participants gave high and similar scores to their own
      willingness to take action to change the situation for both vignettes. The score
      of the internal index was found to be significantly higher than the external
      index. DISCUSSION: The participants' desire to correct a colleague's or
      superior's misconduct was coupled with a progressive retraction as the circle of
      disclosure widened. The retraction may reflect the respondents' concerns that
      external exposure could have negative consequences for the wrong-doer, the
      healthcare organization and/or the individuals who receive its services.

PMID- 22360913
TI  - Ultra-high-performance liquid chromatography-quadrupole/time of flight mass
      spectrometry based chemical profiling approach to rapidly reveal chemical
      transformation of sulfur-fumigated medicinal herbs, a case study on white
      ginseng.
AB  - Sulfur-fumigation may induce chemical transformation of medicinal herbs.
      Development of rapid method to reveal potential sulfur-fumigation induced
      chemical transformation of herbs is a very important issue for efficacy and
      safety of herb application. In present study, a new strategy was proposed to
      rapidly reveal chemical transformation of sulfur-fumigated herbs by ultra-high
      performance liquid chromatography-quadrupole/time of flight mass spectrometry
      (UHPLC-QTOF-MS/MS) based chemical profiling approach. The non-fumigated herb was
      water-wetted and further treated with burning sulfur to get sulfur-fumigated
      herb. Then the chemical fingerprints of both non-fumigated and sulfur-fumigated
      samples were compared by UHPLC-QTOF-MS/MS analysis. The identities of all
      detected peaks, in particular those newly generated in sulfur-fumigated samples
      were confirmed by comparing the mass spectra and retention times of peaks with
      that of reference compounds, and/or tentatively assigned by matching empirical
      molecular formula with that of published compounds, and/or elucidating quasi
      molecular ions and fragment ions referring to available literature information.
      The identification could be rationalized through deducing possible reactions
      involved in the generation of these newly detected compounds. The proposed
      strategy was extensively investigated in the case of white ginseng. Total 82
      components were detected in non-fumigated and sulfur-fumigated white ginseng
      samples, among them 35 sulfur-containing compounds detected only in sulfur
      fumigated white ginseng and its decoction were assigned to be sulfate or sulfite
      derivatives of original ginsenosides, and were deduced to be generated via
      reactions of esterification, addition, hydrolysis and dehydration during sulfur
      fumigation and decocting of white ginseng. The established approach was applied
      to discriminate sulfur-fumigated white ginseng among commercial samples from
      America, Canada, and Hong Kong SAR, Macau SAR and Mainland of China, which
      indicated that the proposed approach is rapid and specific, and should also be
      useful for investigation of potential chemical transformation of other sulfur
      fumigated medicinal herbs.

PMID- 22360914
TI  - Optimization of the liquid chromatography enantioseparation of chiral acidic
      compounds using cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral
      selector and polar organic mobile phases.
AB  - The LC enantioseparation of chiral acidic and zwitterionic drugs selected as
      model compounds was optimized using chlorine containing cellulose based chiral
      stationary phases and polar organic mobile phases. The main solvent of the mobile
      phase was acetonitrile, the temperature was settled at 25 degrees C and a
      stationary phase with cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral
      selector (3-Cl-4-Me-PC) was selected. In the screening step, the nature and
      concentration of both acidic and basic additives were found to have a significant
      effect on retention, selectivity and resolution. Acetic acid (AcA) was selected
      as acidic additive for the optimization step since it could lead to the
      enantioseparation of more acidic compounds than trifluoroacetic acid (TFA) and
      formic acid (FA), while among the three basic additives tested, diethylamine
      (DEA) most often gave better results with respect to enantioresolution and
      selectivity than butylamine (BuA) and triethylamine (TEA). The optimization was
      performed using a central composite face-centered design with two factors, namely
      the concentration of acetic acid (0.1-0.3%) and the concentration of DEA (0.01
      0.1%) in the mobile phase. On the basis of the results obtained in the screening
      and optimization steps, a strategy for the rapid development of methods for the
      enantioseparation of acidic or neutral compounds was proposed.

PMID- 22360915
TI  - Concurrent prophylactic placement of inferior vena cava filter in gastric bypass
      and adjustable banding operations in the Bariatric Outcomes Longitudinal
      Database.
AB  - INTRODUCTION: Postoperative pulmonary embolism (PE) is a leading cause of
      morbidity and mortality after bariatric surgery. However, the concurrent
      prophylactic placement of an inferior vena cava filter (CPIVCF) in patients
      undergoing bariatric operations remains controversial. This study used the
      Bariatric Outcomes Longitudinal Database (BOLD) to establish associated
      characters and determine outcomes of CPIVCF for patients undergoing Roux-en-Y
      gastric bypass (GB) and adjustable gastric banding (AB) surgeries. METHODS: We
      analyzed BOLD, a database of bariatric surgery patient information. GB and AB
      operations were categorized into open and laparoscopic approaches. Univariate
      logistic regressions were used to compare between non-CPIVCF and concurrent
      CPIVCF groups. Significant variables (P < .05) were subsequently input into
      multivariate regression models: CPIVCF was retained in each model. RESULTS: A
      total of 322 CPIVCFs (0.33%) were identified from 97,218 GB and AB operations
      performed between 2007 and 2010 in this retrospective registry study. Significant
      differences were identified in male gender (21.1% vs 31.4%; P < .001),
      preoperative body mass index (BMI; 44.5 +/- 6.6 vs 45.3 +/- 7; P < .001), and
      African-American race (10.5% vs 18%; P < .001) between non-CPIVCF and CPIVCF
      groups. The CPIVCF group had more patients with previous nonbariatric surgery
      (50% vs 43.6%; P = .02), a history of venous thromboembolism (VTE; 21.4% vs 3.1%;
      P < .001), impairment of functional status (7.8% vs 3.1%; P < .001), lower
      extremity edema (47.2% vs 27.1%; P < .001), obesity hypoventilation syndrome
      (7.1% vs 2.1%; P < .001), obstructive sleep apnea syndrome (58.1% vs 43.3%; P <
      .001), and pulmonary hypertension (13% vs 4.1%; P < .001). Patients in the CPIVCF
      group were more likely to receive GB than gastric banding (77% vs 58.1%; P <
      .001) and an open surgical approach (21.4% vs 4.8%; P < .001). Operative duration
      was longer in the CPIVCF group (119 +/- 67 vs 89 +/- 52 minutes; P < .001). The
      CPIVCF group also had a longer length of hospital stay (3 +/- 2 vs 2 +/- 6 days;
      P = .048), was associated with higher incidence of deep venous thrombosis (DVT;
      0.93% vs 0.12%; P < .001), and had a higher mortality (0.31% vs 0.03%; P = .003)
      from PE and indeterminate causes. In multivariate analysis, male gender, African
      American race, previous nonbariatric surgery, a high BMI, obesity hypoventilation
      syndrome, history of VTE, lower extremity edema, and pulmonary hypertension were
      preoperative factors associated with CPIVCF. CONCLUSIONS: CPIVCF was associated
      with specific clinical features, increased health care resource utilization, and
      a higher mortality in patients undergoing bariatric operations. Although selected
      patient characteristics influence surgeons to perform CPIVCF, this study was
      unable to establish an outcome benefit for CPIVCF.

PMID- 22360917
TI  - Ectopic liver masquerading as a floating intracaval mass.
AB  - Ectopic liver is defined as liver parenchyma situated outside the liver proper
      with no connection to native hepatic tissue. This rare developmental anomaly is
      most commonly described as an attachment to the gallbladder with an incidence
      <0.3%, but it has been reported in other locations within the abdomen and
      thorax.(2-4) Most cases are found incidentally in asymptomatic patients, but
      ectopic liver has been known to cause visceral or vascular obstruction.(4,5)
      Herein we present a unique case of ectopic liver attached by a thin stalk
      seemingly floating in the suprahepatic inferior vena cava.

PMID- 22360918
TI  - Ultrasound-guided percutaneous endovascular aneurysm repair success is predicted
      by access vessel diameter.
AB  - OBJECTIVE: Ultrasound scan-guided access allows for direct visualization of the
      access artery during percutaneous endovascular aortic aneurysm repair. We
      hypothesized that the use of ultrasound scan guidance allowed us to safely
      increase the utilization of percutaneous endovascular aortic aneurysm repair to
      almost all patients and decrease access complications. METHODS: A retrospective
      chart review of all elective endovascular aortic aneurysm repairs, both abdominal
      and descending thoracic, from 2005 to 2010 was performed. Patients were
      identified using International Classification of Disease, 9th Revision, Clinical
      Modification Codes and stratified based on access type: percutaneous vs cut-down.
      We examined the success rate of percutaneous access and the cause of failure.
      Sheath size was large (18-24 F) or small (12-16 F). Minimum access vessel
      diameter was also measured. Outcomes were wound complications (infections or
      clinically significant hematomas that delayed discharge or required transfusion),
      operative and incision time, length of stay, and discharge disposition.
      Predictors of percutaneous failure were identified. RESULTS: One hundred sixty
      eight patients (296 arteries) had percutaneous access endovascular aneurysm
      repair (P-EVAR) whereas 131 patients (226 arteries) had femoral cutdown access
      EVAR. Ultrasound scan-guided access was introduced in 2007. P-EVAR increased from
      zero cases in 2005 to 92.3% of all elective cases in 2010. The success rate with
      percutaneous access was 96%. Failures requiring open surgical repair of the
      artery included seven for hemorrhage and six for flow-limiting stenosis or
      occlusion of the femoral artery. P-EVAR had fewer wound complications (0.7% vs
      7.4%; P = .001), shorter operative time (153.3 vs 201.5 minutes; P < .001), and
      larger minimal access vessel diameter (6.7 mm vs 6.1 mm; P < .01). Patients with
      failed percutaneous access had smaller minimal access vessel diameters when
      compared to successful P-EVAR (4.9 mm vs 6.8 mm; P < .001). More failures
      occurred in small sheaths than large ones (7.4% vs 1.9%; P = .02). Access vessel
      diameter <5 mm is predictive of percutaneous failure (16.7% of vessels <5 mm
      failed vs 2.4% of vessels >= 5 mm failed; P < .001; odds ratio, 7.3; 95%
      confidence interval, 1.58-33.8; P = .01). CONCLUSIONS: Ultrasound scan-guided P
      EVAR can be performed in the vast majority of patients with a high success rate,
      shorter operative times, and fewer wound complications. Access vessel diameters
      <5 mm are at greater risk for percutaneous failure and should be treated
      selectively.

PMID- 22360919
TI  - Comparing patient outcomes between multiple ipsilateral iliac artery stents and
      isolated iliac artery stents.
AB  - OBJECTIVE: Endovascular stents are accepted therapy for iliac artery stenoses and
      occlusions. Surgery is the recommended therapy for patients with severe iliac
      artery disease, including those with the combination of ipsilateral common iliac
      artery (CIA) and external iliac artery (EIA) stenoses/occlusions. This study
      compared patient outcomes, including late open conversion rates, for combined
      ipsilateral CIA and EIA stenting vs CIA or EIA stents alone. METHODS: Between
      1998 and 2010, 588 patients underwent iliac artery stenting at two institutions.
      Patient comorbidities and outcomes were retrospectively reviewed, and analyses
      were performed using multivariate regression and Kaplan-Meier methods. RESULTS:
      There were 436 extremities with CIA stents, 195 with EIA stents, and 157 with CIA
      and EIA stents. The groups did not differ significantly in demographics,
      comorbidities, or treatment indications. During follow-up, 183 patients died, 95
      underwent an endovascular reintervention, and 48 required late open conversion.
      For patients in the CIA or EIA stent group, the mean +/- standard error survival
      was 5.3 +/- 0.3 years, secondary endovascular intervention-free survival was 7.4
      +/- 0.6 years, late open conversion-free survival was 9.8 +/- 0.4 years, and
      amputation-free survival was 7.6 +/- 0.4 years. In the CIA and EIA stent group,
      survival was 6.1 +/- 0.6 years, secondary endovascular intervention-free survival
      was 7.2 +/- 0.6 years, late open conversion-free survival was 9.0 +/- 1.1 years,
      and amputation-free survival was 8.4 +/- 0.5 years. Survival, reintervention-free
      survival, late open conversion-free survival, and amputation-free survival were
      all similar between patient groups (all P > .05). CIA and EIA stenting in
      combination was not a predictor of death, reintervention, late open conversion,
      or amputation. CONCLUSIONS: Outcomes are similar for patients with CIA or EIA
      stents and for those with combined ipsilateral CIA and EIA stents. Late open
      conversions for iliac artery stent failure are uncommon and not influenced by the
      location or extent of prior iliac artery stent placement. Endovascular therapy
      for aortoiliac disease should be extended to consider selected patients with
      ipsilateral CIA and EIA stenoses/occlusions.

PMID- 22360920
TI  - Cardiovascular risk and combined oral contraceptives: clinical decisions in
      settings of uncertainty.
AB  - Although generally safe, combined oral contraceptives (COCs) are associated with
      risks, including an estimated 2-fold increased relative risk of cardiovascular
      events. For most women taking COCs for contraception, absolute cardiovascular
      risks are very low, and the overall risks of COCs are outweighed by the risks of
      unwanted pregnancy. Nonetheless, risks of COCs may be excessive in some women,
      and both the American College of Obstetricians (ACOG) and the World Health
      Organization (WHO) have offered contraindications for COC use. Complicating this
      issue, COCs are commonly used for reasons other than contraception (eg,
      polycystic ovary syndrome, which is associated with subfertility and
      cardiovascular risk factors). Thus, in some clinical scenarios, ACOG and WHO
      guidelines may offer incomplete guidance regarding whether COC use would be
      associated with an unacceptable risk-benefit ratio. We propose that
      cardiovascular risk calculators may be helpful in some patients, as an adjunct to
      ACOG and WHO guidelines, by allowing physicians to estimate the attributable risk
      of COC-related cardiovascular events.

PMID- 22360921
TI  - The adipokine apelin and human uterine contractility.
AB  - OBJECTIVE: Obesity is an increasing problem in obstetric practice. Apelin,
      secreted by adipocytes, is present in increased serum concentrations in an obese
      state. Our group has previously highlighted that the adipokines leptin and
      ghrelin have a potential role in metabolic modulation of uterine contractility in
      obese women. The aim of this study was to evaluate the effects of apelin on human
      uterine contractility in vitro. STUDY DESIGN: Biopsies of human myometrium were
      obtained at elective cesarean section. Myometrial strips suspended under
      isometric conditions, undergoing spontaneous and oxytocin-induced contractions,
      were exposed to cumulative additions of apelin in the concentration range of 1
      nmol/L to 1 MUmol/L. Control experiments were performed simultaneously. RESULTS:
      Apelin exerted an inhibitory effect on spontaneous and oxytocin induced
      contractions in human myometrium. The mean maximal inhibition values were 36.8 +/
      6.4% for spontaneous (n = 6; P = .002) and 30.4 +/- 4.6% for oxytocin-induced
      contractions (n = 6; P < .0001). CONCLUSION: Apelin inhibits human uterine
      contractility in vitro, raising the possibility that such metabolic modulation
      may play a physiological role in obese parturients.

PMID- 22360922
TI  - A novel training model for the loop electrosurgical excision procedure: an
      innovative replica helped workshop participants improve their LEEP.
AB  - We wanted to evaluate the feasibility and effect of a hands-on loop
      electrosurgical excision procedure (LEEP) 2.5-day intensive surgical skills
      workshop, using a novel training model on porcine tissue. Hands-on simulation
      based training was conducted to emphasize colposcopy, local anesthesia, uterine
      cervix and vulva punch biopsy, LEEP, and complication management. Performance of
      51 participants' technical skills was assessed before and after training
      completion. LEEP performance was significantly better after completion of the
      training (P < .001). Before and after training mean scores (SD) of 18.0 (3.5) and
      23.4 (2.1) were assessed. Multivariate analysis revealed that the training
      effects were independent of previous surgical expertise. The LEEP workshop was
      feasible and effective and we recommend implementing hands-on LEEP training into
      gynecology training programs.

PMID- 22360923
TI  - FGF23/Klotho axis: phosphorus, mineral metabolism and beyond.
AB  - In this work we summarizes the steps that allowed the identification of the
      fibroblast growth factor (FGF) 23/Klotho axis as the principal regulator of
      phosphate homeostasis, exerting actions on intestine, bone, parathyroid glands,
      and kidney. We review the not fully understood mechanisms of action of this axis
      on the regulation of mineral homeostasis and, in addition, we discuss its
      potential role in the pathophysiology of chronic kidney disease and the
      associated complications. We also reflect the actual tendency to consider the
      components of this system as better predictors of the pathological conditions
      frequently associated to mineral disorders, and review some recent studies
      linking these components to cardiovascular disease even in population without
      mineral disorders. Finally, we consider the numerous processes in which Klotho is
      involved, including anti-ageing and mineral control processes, independently of
      its functions as obligated-coreceptor for FGF23.

PMID- 22360924
TI  - The impact of luteal phase support on endometrial estrogen and progesterone
      receptor expression: a randomized control trial.
AB  - BACKGROUND: To assess the impact of luteal phase support on the expression of
      estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the
      endometrium of oocyte donors undergoing controlled ovarian hyperstimulation
      (COH). METHODS: A prospective, randomized study was conducted in women undergoing
      controlled ovarian hyperstimulation for oocyte donation. Participants were
      randomized to receive no luteal support, vaginal progesterone alone, or vaginal
      progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies
      were obtained at 4 time points in the luteal phase and evaluated by tissue
      microarray for expression of ER alpha and PR-B. RESULTS: One-hundred and eight
      endometrial tissue samples were obtained from 12 patients. No differences were
      found in expression of ER alpha and PR-B among all the specimens with the
      exception of one sample value. CONCLUSIONS: The administration of progesterone
      during the luteal phase of COH for oocyte donor cycles, either with or without
      estrogen, does not significantly affect the endometrial expression of ER alpha
      and PR.

PMID- 22360925
TI  - Lipoprotein composition in HNF1A-MODY: differentiating between HNF1A-MODY and
      type 2 diabetes.
AB  - INTRODUCTION: The young-onset diabetes seen in HNF1A-MODY is often misdiagnosed
      as Type 2 diabetes. Type 2 diabetes, unlike HNF1A-MODY, is associated with
      insulin resistance and a characteristic dyslipidaemia. We aimed to compare the
      lipid profiles in HNF1A-MODY, Type 2 diabetes and control subjects and to
      determine if lipids can be used to aid the differential diagnosis of diabetes sub
      type. METHODS: 1) 14 subjects in each group (HNF1A-MODY, Type 2 diabetes and
      controls) were matched for gender and BMI. Fasting lipid profiles and HDL lipid
      constituents were compared in the 3 groups. 2) HDL-cholesterol was assessed in a
      further 267 patients with HNF1A-MODY and 297 patients with a diagnosis of Type 2
      diabetes to determine its discriminative value. RESULTS: 1) In HNF1A-MODY
      subjects, plasma-triglycerides were lower (1.36 vs. 1.93 mmol/l, p = 0.07) and
      plasma-HDL-cholesterol was higher than in subjects with Type 2 diabetes (1.47 vs.
      1.15 mmol/l, p = 0.0008), but was similar to controls. Furthermore, in the
      isolated HDL; HDL-phospholipid and HDL-cholesterol ester content were higher in
      HNF1A-MODY, than in Type 2 diabetes (1.59 vs. 1.33 mmol/L, p = 0.04 and 1.10 vs.
      0.83 mmol/L, p = 0.019, respectively), but were similar to controls (1.59 vs.
      1.45 mmol/L, p = 0.35 and 1.10 vs. 1.21 mmol/L, p = 0.19, respectively). 2) A
      plasma-HDL-cholesterol > 1.12 mmol/L was 75% sensitive and 64% specific (ROC AUC
      = 0.76) at discriminating HNF1A-MODY from Type 2 diabetes. CONCLUSION: The plasma
      lipid profiles of HNF1A-MODY and the lipid constituents of HDL are similar to non
      diabetic controls. However, HDL-cholesterol was higher in HNF1A-MODY than in Type
      2 diabetes and could be used as a biomarker to aid in the identification of
      patients with HNF1A-MODY.

PMID- 22360926
TI  - Remembering two among us.

PMID- 22360927
TI  - Characteristics of HIV-infected mothers associated with increased risk of poor
      mother-infant interactions and infant outcomes.
AB  - INTRODUCTION: The current study aimed to investigate the relationship between
      individual and familial characteristics of HIV-infected mothers and their
      psychological health as it relates to parenting as well as their parenting
      beliefs/abilities. METHOD: A descriptive correlational design was used. Seventeen
      HIV-infected mothers and their infants were recruited from a university clinic in
      Alabama. Assessments were gathered at the infant's pediatric clinic appointments
      (approximately 6 weeks after delivery) and included a demographic questionnaire,
      the Beck Depression Inventory-II, the Maternal Confidence Questionnaire, the
      Parenting Stress Index-Short Form, and the Questionnaire About Physical Contact.
      RESULTS: Dysfunctional parent-child interactions significantly correlated with
      maternal confidence, parent stress, and overall feeling about physical contact.
      Difficult child temperament correlated with overall and current feelings of
      physical contact and parent stress. Significant correlations were found between
      parent distress, parent stress, and maternal depression. DISCUSSION: Beyond the
      need to assist HIV-infected mothers with stress and depression, an intervention
      is needed to facilitate optimal parent-child interactions and improve both child
      psychosocial and cognitive outcomes.

PMID- 22360928
TI  - Uptake of the human papillomavirus vaccine: a review of the literature and report
      of a quality assurance project.
AB  - PURPOSE: The aims of this study were to review predictors of knowledge about
      human papillomavirus (HPV), HPV vaccine, and factors related to HPV vaccine
      uptake and report a quality assurance project that evaluated HPV vaccine uptake
      and three-dose completion rates. METHODS: The setting was a small private urban
      pediatric practice. Chart review was used to describe HPV vaccine uptake and dose
      completion rates in 2007. The convenience sample included 189 girls aged 12 to 21
      years with HPV vaccine uptake. RESULTS: During 2007, 153 girls aged 12 to 17
      years and 42 girls aged 18 to 21 years were seen at well-child care visits. HPV
      vaccine uptake was 72% (n = 110) for the younger group and 79% (n = 33) for the
      older group. There was no significant difference in HPV vaccine uptake by group.
      One quarter (24%, n = 46) received the HPV vaccine dose at an episodic visit. The
      dose completion rate was 64% (n = 120). DISCUSSION: HPV vaccine uptake and dose
      completion rates were higher than rates reported by the Centers for Disease
      Control and Prevention. Effective strategies are needed to promote HPV vaccine
      uptake and dose completion.

PMID- 22360929
TI  - Interpersonal violence: secondary analysis of the keep your children/yourself
      safe and secure (KySS) data.
AB  - INTRODUCTION: The purpose of the secondary analysis was to determine agreement of
      parents and children to the interpersonal violence (IPV) items on the Keep Your
      Children/Yourself Safe and Secure (KySS) survey to assess mental health concerns.
      METHODS: A comparative, descriptive design was used to determine the level of
      agreement between parent/child dyads on the 15 attitude/knowledge and worry items
      related to IPV (n = 563 dyads). RESULTS: Single mother/son and 10- to 12-year
      olds had less agreement than other dyad combinations and child age groups. Six of
      the 10 knowledge/attitude items had significant differences, including
      multigenerational occurrence of sexual abuse, the effect of harsh parenting,
      witnessing domestic violence, and incidence of physical abuse. The least
      agreement was on sexual abuse, incidence of physical abuse, and outcome of strict
      parenting (p < .001). Parents had greater worry about the parent-child
      relationship than did the children (p < .001). DISCUSSION: Parents and clinicians
      may not realize how different their understanding of IPV is from that of
      children. Identifying items of least agreement can inform parents and clinicians
      in targeting violence education and prevention.

PMID- 22360930
TI  - Screening for depression and help-seeking in postpartum women during well-baby
      pediatric visits: an integrated review.
AB  - PURPOSE: The purposes of this integrated review are to examine the literature on
      screening for depression and help-seeking behaviors by postpartum women during
      pediatric well-baby visits; to identify gaps in the literature relating to
      depression and help-seeking behaviors; and to discuss implications for practice
      and future research. METHOD: An extensive search of primary source documents was
      conducted in Academic Search Premier, CINAHL, MEDLINE, Mental Measurements
      Yearbook, PsycINFO, PsycARTICLES, and Women's Studies International using the key
      words postpartum, postpartum depression (PPD), help seeking, and pediatric
      setting or pediatrician. Thirty-five articles relevant to help seeking, PPD, and
      screening in the pediatric setting were included in this review. Research studies
      included both quantitative and qualitative articles. RESULTS: PPD affects 10% to
      15% of all women after birth. Postpartum women generally do not seek help for
      depression. Untreated PPD has significant adverse affects on parenting, maternal
      bonding, and the infant's emotional and behavioral development. Interaction with
      the woman's obstetric provider ends shortly after the baby's birth. However,
      interactions with the pediatric office are initiated and continue throughout the
      infant's first two years of life. DISCUSSION: Early recognition of PPD and
      appropriate treatment are imperative for positive maternal-infant outcomes. A
      majority of women do not seek help for depression from any source. Because
      mothers have routine interactions with pediatric office staff during the first
      few years after giving birth, pediatric nurse practitioners and pediatricians
      have the perfect opportunity to screen and educate women regarding symptoms,
      treatment, and available resources for PPD.

PMID- 22360931
TI  - The experiences of school-age children with a tracheostomy.
AB  - PURPOSE: The purpose of this study was to explore the school-age child's
      perspective about living with a tracheostomy. DESIGN AND METHODS: A qualitative
      design using phenomenological methods was used to describe and interpret the
      lived experiences of school-age children with a tracheostomy. RESULTS: The
      perceptions of five children were explored, and three themes emerged: "I'm the
      only one," "friends are helpful," and "just tell them." CONCLUSIONS: Data
      indicated that encouraging friendships with other children enhances the well
      being of the child with a tracheostomy. In addition, data suggested that when
      schoolmates understand the experiences of children with tracheostomies, they are
      supportive of the child. Nurse practitioners are in a unique position to assist
      the child with a tracheostomy in the development of peer networks.

PMID- 22360932
TI  - A primary care healthy choices intervention program for overweight and obese
      school-age children and their parents.
AB  - INTRODUCTION: The escalating crisis of childhood overweight and obesity creates
      an urgent demand for evidence-based interventions that can be used by primary
      care providers. Therefore, the purpose of this study was to test the feasibility,
      acceptability, and preliminary efficacy of a theory-based Healthy Choices
      Intervention (HCI) Program with fifteen 9-12 year old overweight and obese
      children and their parents in a primary care setting. METHODS: A 1-group, 7-week
      pre-/posttest study design was used. Outcome measures included: body mass index
      (BMI) percentile, physical activity and nutrition knowledge, beliefs, choices and
      behaviors, anxiety, depression, self-concept, and social competence. RESULTS:
      Children and parents found the HCI to be useful and informative. Positive effects
      of the HCI for the children included decreased BMI percentile, increased
      knowledge, beliefs, choices and behaviors, and self-control. Positive effects of
      the intervention for the parents included increased knowledge, beliefs,
      behaviors, and decreased anxiety. DISCUSSION: This study provides evidence to
      support the feasibility, acceptability, and preliminary effects of the HCI with
      overweight and obese school-age children and their parents within a primary care
      setting.

PMID- 22360933
TI  - Antipsychotic medication prescribing trends in children and adolescents.
AB  - The Food and Drug Administration has approved the use of antipsychotic
      medications in some children and adolescents with severe emotional and behavioral
      disorders. However, recent national data show a dramatic rise in off-label and
      Food and Drug Administration-approved uses of these medications. Of particular
      note is a twofold to fivefold increase in the use of antipsychotic medications in
      preschool children, despite little information on their long-term effects. This
      article describes the trend in pediatric antipsychotic medication use, possible
      explanations for the increase, implications for children's health, and
      recommendations for pediatric providers who work with parents of children and
      adolescents who seek or receive antipsychotic medication treatments.

PMID- 22360934
TI  - Blepharoptosis: assessment and management.

PMID- 22360935
TI  - Chemicals in daily life: emerging evidence on the impact on child health.

PMID- 22360936
TI  - The Analgesia Nociception Index: a pilot study to evaluation of a new pain
      parameter during labor.
AB  - BACKGROUND: Objective pain assessment that is not subject to influences from
      either cultural or comprehension issues is desirable. Analysis of heart rate
      variability has been proposed as a potential method. This pilot study aimed to
      assess the performance of the PhysioDolorisTM analgesia monitor which calculates
      an Analgesia Nociception Index derived from heart rate variability. It was
      compared with visual analogical pain scores. METHODS: Forty-five parturients who
      requested epidural analgesia were recruited. Simultaneous couplets of pain scores
      and Analgesia Nociception Index values were recorded every 5 min regardless of
      the presence or absence of uterine contractions. The relationship between indices
      was characterized, and a cut-off value of Analgesia Nociception Index
      corresponding to a visual analogical score >30 (range 0-100) was used to
      determine the positive and negative predictive value of the Analgesia Nociception
      Index. RESULTS: There was a negative linear relationship between visual
      analogical pain scores and Analgesia Nociception Index values regardless of the
      presence of uterine contractions (regression coefficient +/- SEM=-0.18 +/- 0.032
      for entire dataset). Uterine contraction significantly reduced the Analgesia
      Nociception Index (P<0.0001). Using a visual analogical pain score >30 to define
      a painful sensation, the lower 95% confidence limit for the Analgesia Nociception
      Index score was 49. CONCLUSION: The Analgesia Nociception Index has an inverse
      linear relationship with visual analogical pain scores. Further studies are
      necessary to confirm the results of this pilot study and to look at the influence
      of epidural analgesia on the Analgesia Nociception Index.

PMID- 22360937
TI  - Developmental toxicity evaluation of three hexabromocyclododecane
      diastereoisomers on zebrafish embryos.
AB  - Structural dissimilarities of hexabromocyclododecane diastereoisomers could raise
      substantial differences in physicochemical, biological and toxicological
      properties. In order to fully assess the environmental safety and health risk of
      hexabromocyclododecanes (HBCDs), zebrafish embryos were used to evaluate the
      developmental toxicity of individual HBCD diastereoisomers (alpha-HBCD, beta-HBCD
      and gamma-HBCD). Four-hour post-fertilization (hpf) zebrafish embryos were
      exposed to different concentrations of HBCD diastereoisomers (0, 0.01, 0.1 and
      1.0 mg/l) until 120 hpf. The results showed that exposure to HBCDs can affect the
      development of zebrafish embryos/larvae in a dose-dependent and
      diastereoselective manner. The diastereoisomers alpha-, beta- and gamma-HBCD at
      0.01 mg/l had little effect on the development of zebrafish embryos except that
      exposure to 0.01 mg/l gamma-HBCD significantly delayed hatching (P<0.05). At
      0.1mg/l, alpha-HBCD resulted in depressed heart rate of larvae (96 hpf) and
      delayed hatching, whereas beta- and gamma-HBCD both caused significant hatching
      delay and growth inhibition (P<0.05). In addition, a remarkable and significant
      increase in mortality and malformation rate was noted at 0.1 mg/l gamma-HBCD
      exposure groups (P<0.05). At 1.0 mg/l, alpha-, beta- and gamma-HBCD significantly
      affected all of the endpoints monitored (P<0.05). Additionally, HBCD
      diastereoisomers could induce the generation of reactive oxygen species (ROS) and
      the activities of caspase-3 and caspase-9 in a dose-dependent manner. The results
      indicated that HBCD diastereoisomers could cause developmental toxicity to
      zebrafish embryos through inducing apoptosis by ROS formation. The overall
      results showed a good agreement confirming that the order of developmental
      toxicity of HBCD diastereoisomers in zebrafish is gamma-HBCD>beta-HBCD>alpha
      HBCD.

PMID- 22360938
TI  - Identification and characterization of zebrafish SULT1 ST9, SULT3 ST4, and SULT3
      ST5.
AB  - By searching the GenBank database, we identified sequences encoding three new
      zebrafish cytosolic sulfotransferases (SULTs). These three new zebrafish SULTs,
      designated SULT1 ST9, SULT3 ST4, and SULT3 ST5, were cloned, expressed, purified,
      and characterized. SULT1 ST9 appeared to be mostly involved in the metabolism and
      detoxification of xenobiotics such as beta-naphthol, beta-naphthylamine, caffeic
      acid and gallic acid. SULT3 ST4 showed strong activity toward endogenous
      compounds such as dehydroepiandrosterone (DHEA), pregnenolone, and 17beta
      estradiol. SULT3 ST5 showed weaker, but significant, activities toward endogenous
      compounds such as DHEA and corticosterone, as well as xenobiotics including
      mestranol, beta-naphthylamine, beta-naphthol, and butylated hydroxyl anisole
      (BHA). pH-dependency and kinetic constants of these three enzymes were determined
      with DHEA, beta-naphthol, and 17beta-estradiol as substrates. Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed to examine the
      expression of these three new zebrafish SULTs at different developmental stages
      during embryogenesis, through larval development, and on to maturity.

PMID- 22360939
TI  - In vivo studies on inhibition and recovery of B-esterase activities in
      Biomphalaria glabrata exposed to azinphos-methyl: analysis of enzyme, substrate
      and tissue dependence.
AB  - Cholinesterases and carboxylesterases belong to the group of B-esterases, the
      serine superfamily of esterases that are inhibited by organophosphorus compounds.
      It is now generally accepted that before using the B-esterases as biomarkers of
      exposure to organophosphorus and carbamates in a given species, the biochemical
      characteristics of these enzymes should be carefully studied. In this study, the
      enzyme/s and the tissue/s to be selected as sensitive biomarkers of
      organophosphorus exposition in the freshwater gastropod Biomphalaria glabrata
      were investigated. Firstly, the substrate dependence of cholinesterase and
      carboxylesterase activities in whole organism soft tissue and in different
      tissues of the snail (head-foot, pulmonary region, digestive gland, and gonads)
      was analyzed. Measurements of cholinesterase activity were performed using three
      substrates: acetylthiocholine (AcSCh), propionylthiocholine (PrSCh), and
      butyrylthiocholine (BuSCh). Carboxylesterase activity was determined using four
      different substrates: 1-naphthyl acetate (1-NA), 2-naphthyl acetate (2-NA), p
      nitrophenyl acetate (p-NPA), and p-nitrophenyl butyrate (p-NPB). Regardless of
      the tissue analyzed, the highest specific activity was obtained when using AcSCh,
      followed by PrSCh. Cholinesterase activity measured with BuSCh was very low in
      all cases. On the other hand, the highest cholinesterase activity was measured in
      head-foot and in pulmonary region, representing in the case of AcSCh hydrolysis
      196% and 180% of the activity measured in whole organism soft tissue,
      respectively. In contrast, AcSCh hydrolysis in digestive gland and gonads was 28%
      and 50% of that measured in whole organism soft tissue. Regarding
      carboxylesterase activity, although all tissues hydrolyzed the four substrates
      assayed, substrate preferences varied among tissues. In particular, digestive
      glands showed higher carboxylesterase activity than the other tissues (299%, 359%
      and 137% of whole organism soft tissue activity) when measured with 1-NA, 2-NA
      and p-NPA as substrates, respectively. In contrast, with p-NPB as substrate, the
      highest carboxylesterase activity was observed in pulmonary region. Exposure of
      the snails for 48 h to azinphos-methyl concentrations in the range of 0.05-2.5 mg
      L-1 resulted in different degrees of inhibition of cholinesterase and
      carboxylesterase activities, depending on the enzyme, pesticide concentration,
      the substrate, and the tissue analyzed. In general, carboxylesterase activity
      measured with p-NPA and p-NPB was much more sensitive to azinphos-methyl
      inhibition than cholinesterase activity. The results also showed that while B
      esterase activities in whole organism soft tissue and pulmonary region recovered
      completely within 14 days, carboxylesterase activity in digestive glands remained
      highly inhibited. On the whole, the results of the present study emphasize how
      important it is to characterize and measure cholinesterase and carboxylesterase
      activities jointly to make a proper assessment of the impact of organophosphorus
      pesticides in non-target species.

PMID- 22360940
TI  - Differences in sexual development in inbred and outbred zebrafish (Danio rerio)
      and implications for chemical testing.
AB  - Outbred laboratory animal strains used in ecotoxicology are intended to represent
      wild populations. However, breeding history may vary considerably between
      strains, driving differences in genetic variation and phenotypes used for
      assessing effects of chemical exposure. We compared a range of phenotypic
      endpoints in zebrafish from four different "breeding treatments" comprising a
      Wild Indian Karyotype (WIK) zebrafish strain and a WIK/Wild strain with three
      levels of inbreeding (F(IT)=n, n+0.25, n+0.375) in a new Fish Sexual Development
      Test (FSDT). There were no differences between treatments in terms of egg
      viability, hatch success or fry survival. However, compared with WIKs, WIK/Wild
      hybrids were significantly larger in size, with more advanced gonadal (germ cell)
      development at the end of the test (63 days post fertilisation). Increasing the
      levels of inbreeding in the related WIK/Wild lines did not affect body size, but
      there was a significant male-bias (72%) in the most inbred line (F(IT)=n+0.375).
      Conversely, in the reference WIK strain there was a significant female-bias in
      the population (80% females). Overall, our results support the use of outbred
      zebrafish strains in the FSDT, where one of the core endpoints is sex ratio.
      Despite increased variance (and reduced statistical power) for some endpoints,
      WIK/Wild outbreds (F(IT)=n) met all acceptance criteria for controls in this
      test, whereas WIKs failed to comply with tolerance limits for sex ratio (30-70%
      females). Sexual development was also more advanced in WIK/Wild outbreds (cf.
      WIKs), providing greater scope for detection of developmental reproductive
      toxicity following chemical exposure.

PMID- 22360942
TI  - Quantitative methods for the analysis of zoosporic fungi.
AB  - Quantitative estimations of zoosporic fungi in the environment have historically
      received little attention, primarily due to methodological challenges and their
      complex life cycles. Conventional methods for quantitative analysis of zoosporic
      fungi to date have mainly relied on direct observation and baiting techniques,
      with subsequent fungal identification in the laboratory using morphological
      characteristics. Although these methods are still fundamentally useful, there has
      been an increasing preference for quantitative microscopic methods based on
      staining with fluorescent dyes, as well as the use of hybridization probes. More
      recently however PCR based methods for profiling and quantification (semi- and
      absolute) have proven to be rapid and accurate diagnostic tools for assessing
      zoosporic fungal assemblages in environmental samples. Further application of
      next generation sequencing technologies will however not only advance our
      quantitative understanding of zoosporic fungal ecology, but also their function
      through the analysis of their genomes and gene expression as resources and
      databases expand in the future. Nevertheless, it is still necessary to complement
      these molecular-based approaches with cultivation-based methods in order to gain
      a fuller quantitative understanding of the ecological and physiological roles of
      zoosporic fungi.

PMID- 22360941
TI  - Development of liposome gel based formulations for intravaginal delivery of the
      recombinant HIV-1 envelope protein CN54gp140.
AB  - Mucosally-administered vaccine strategies are widely investigated as a promising
      means of preventing HIV infection. This study describes the development of
      liposomal gel formulations, and novel lyophilised variants, comprising HIV-1
      envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged
      or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean
      vesicle diameter, polydispersity, morphology, zeta potential and antigen
      encapsulation efficiency before being incorporated into hydroxyethyl cellulose
      (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid
      dosage form for practical vaginal application. The lyophilised liposome-HEC rods
      were evaluated for moisture content and redispersibility in simulated vaginal
      fluid. Since these rods are designed to revert to gel form following intravaginal
      application, mucoadhesive, mechanical (compressibility and hardness) and
      rheological properties of the reformed gels were evaluated. The liposomes
      exhibited good encapsulation efficiency and the gels demonstrated suitable
      mucoadhesive strength. The freeze-dried liposome-HEC formulations represent a
      novel formulation strategy that could offer potential as stable and practical
      dosage form.

PMID- 22360943
TI  - Is possible to prevent the post-pericardiotomy syndrome?
AB  - The post-pericardiotomy syndrome (PPS) is not uncommon following cardiac surgery
      and may be a cause of severe complications (cardiac tamponade, large pleural
      effusion), hospital stay prolongation, and readmissions. The estimated incidence
      of the syndrome has a relatively wide range affecting from 10 to 40% of patients,
      depending on the adopted diagnostic criteria, institution, and type of cardiac
      surgery. On this basis, there is a need for standardized criteria for
      epidemiological and clinical purposes. These criteria should be adopted in future
      clinical trials and studies on the PPS as well. Such criteria should include both
      clinical and instrumental findings considering the spectrum of pleuropericardial
      involvement of the syndrome. In any case, pharmacologic preventive strategies are
      worthy of further investigation. At present, data from 2 RCTs enrolling a total
      of 471 patients, have shown that colchicine was associated with a reduced risk of
      PPS (OR=0.38 95% CI 0.22 to 0.65). Available evidence suggests that colchicine
      0.5-1.0mg/day is effective for reducing recurrences of pericarditis and at the
      same doses is efficacious to prevent the PPS.

PMID- 22360944
TI  - Effects of percutaneous coronary intervention and stenting with different drug
      eluting coatings and platforms on endothelial damage and inflammation.

PMID- 22360946
TI  - A Poiseuille-based coronary angiographic index for prediction of fractional flow
      reserve.
AB  - BACKGROUND: Coronary revascularization is commonly based on the angiographic
      finding of percent diameter stenosis (%DS) >50 while lesion length (LL), which
      contributes to flow-limitation according to Poiseuille's equation, is
      disregarded. Fractional flow reserve (FFR) is superior to assessment of %DS for
      identifying flow-limiting lesions, but the technology is invasive and relatively
      expensive. We developed a Poiseuille-based angiographic index, incorporating both
      minimal lumen diameter (MLD) and LL, for improved assessment of the hemodynamic
      significance of intermediate coronary lesions. The present study was designed to
      test the hypothesis that the Poiseuille-based angiographic index correlated
      better with FFR measurements than angiographic assessment of %DS. METHODS: We
      performed quantitative coronary angiography (QCA) and FFR measurements in 46
      intermediate coronary lesions in 41 symptomatic patients referred for diagnostic
      coronary angiography. From QCA we determined LL, MLD and %DS and calculated an
      angiographic index, the LL/MLD(4) ratio. RESULTS: Mean LL was 14.2 +/- 7.8
      (range: 4.3-38.8) mm, MLD 1.4 +/- 0.4 (range: 0.6-2.3) mm, %DS 46 +/- 12 (range:
      25-74) and FFR 0.85 +/- 0.09 (range: 0.55-1.00). Fractional flow reserve
      correlated inversely with %DS (R=-0.39, p=0.008) and with the LL/MLD(4) ratio (R=
      0.66, p<0.0001). An FFR cut-off value of 0.80 corresponded with a LL/MLD(4) ratio
      of 12 (p=0.003) but not with a %DS of 50 (p=NS). A LL/MLD(4) ratio <= 12 had a
      specificity of 94% and negative predictive value of 82% for excluding
      hemodynamically significant lesions with FFR (>= 0.80). CONCLUSIONS: The
      LL/MLD(4) ratio was superior to standard angiographic measurement of %DS for
      exclusion of hemodynamically significant coronary lesions.

PMID- 22360945
TI  - Incidence and predictors of coronary stent thrombosis: evidence from an
      international collaborative meta-analysis including 30 studies, 221,066 patients,
      and 4276 thromboses.
AB  - BACKGROUND: Stent thrombosis remains among the most feared complications of
      percutaneous coronary intervention (PCI) with stenting. However, data on its
      incidence and predictors are sparse and conflicting. We thus aimed to perform a
      collaborative systematic review on incidence and predictors of stent thrombosis.
      METHODS: PubMed was systematically searched for eligible studies from the drug
      eluting stent (DES) era (1/2002-12/2010). Studies were selected if including >=
      2000 patients undergoing stenting or reporting on >= 25 thromboses. Study
      features, patient characteristics, and incidence of stent thrombosis were
      abstracted and pooled, when appropriate, with random-effect methods (point
      estimate [95% confidence intervals]), and consistency of predictors was formally
      appraised. RESULTS: A total of 30 studies were identified (221,066 patients, 4276
      thromboses), with DES used in 87%. After a median of 22 months, definite,
      probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with
      acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%;
      0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for
      studies reporting only on DES. From a total of 47 candidate variables,
      definite/probable stent thrombosis was more commonly and consistently predicted
      by early antiplatelet therapy discontinuation, extent of coronary disease, and
      stent number/length, with acute coronary syndrome at admission, diabetes, smoking
      status, and bifurcation/ostial disease also proving frequent predictors, but less
      consistently. CONCLUSIONS: Despite numerous possible risk factors, the most
      common and consistent predictors of stent thrombosis are early antiplatelet
      therapy discontinuation, extent of coronary disease, and stent number/length.

PMID- 22360947
TI  - Poor sleep quality and reduced cognitive function in persons with heart failure.

PMID- 22360948
TI  - The cardioprotective effects of erythropoietin in myocardial ischemic injury via
      upregulation of SDF-1 by JAK2/STAT3.

PMID- 22360949
TI  - Atorvastatin therapy reduces serum uric acid levels: a meta-analysis of
      randomized controlled trials.

PMID- 22360950
TI  - Left ventricular glomangioma.

PMID- 22360951
TI  - A potential skin substitute constructed with hEGF gene modified HaCaT cells for
      treatment of burn wounds in a rat model.
AB  - This study aimed to investigate the feasibility of using an immortal keratinocyte
      cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a
      skin substitute to treat burn wounds. The skin equivalent was constructed with
      human EGF (hEGF) gene modified HaCaT cells obtained through stable gene
      transfection; these were applied to full thickness burn wounds in a rat model.
      The results showed that the hEGF gene modified HaCaT cells produced more than
      390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-beta1 as
      keratinocyte differentiation markers were elevated in the hEGF gene modified
      HaCaT cells which were shown to be non-tumorigenic. The skin equivalent
      constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal
      morphogenesis with a thick and compact epidermis. Wound healing was accelerated
      noticeably when applied with this skin substitute seeded with hEGF gene modified
      HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene
      might be promising seed cells for construction of genetically modified skin
      substitute which can effectively secrete hEGF to accelerate wound repair and
      regeneration.

PMID- 22360952
TI  - Association between depression, patient scar assessment and burn-specific health
      in hospitalized burn patients.
AB  - BACKGROUND: Depression is one of the most common psychological problems arising
      after a burn, but its relationship with patient scar assessment and burn-specific
      health are poorly understood. The aim of this study was to identify the incidence
      of in-hospital symptoms of depression, compare level of patient scar assessment,
      and burn-specific health by depression cutoff point, and identify the
      relationship between depression and these variables. METHODS: In a cross
      sectional descriptive study, 113 burn patients from two inpatient burn centers
      were divided into two groups based on the cutoff point of the Korean Center for
      Epidemiologic Studies Depression Scale (Korean CES-D): >=25 or <25. Patient Scar
      Assessment Scale and Korean Burn-Specific Health Scale-Brief (BSHS-B-K) were used
      to identify associations with depression. RESULTS: Incidence of severe, definite
      depression as assessed by a score of 25 or above on the Korean CES-D was
      approximately 50% on an average at 60.9 days after injury. Burn patients with the
      Korean CES-D>=25 had significantly higher total mean patient scar assessment
      scores (43.34+/-11.49 vs. 36.84+/-9.56, t=3.265, p=.001), and lower burn-specific
      health subscale scores compared to patients with Korean CES-D<25. Depression was
      positively correlated with all subscales of the Patient Scar Assessment, ranging
      from r=.196 to .335 except scar color. Depression was significantly correlated
      with all subscales of the BSHS-B-K, range from r=-.320 to -.725. CONCLUSION:
      Results indicate that incidence of symptoms of depression is relatively high, and
      depressed burn patients report worse burn scar or sensation and lower levels of
      burn-specific health. Early, timely recognition and management of depression in
      these patients are warranted.

PMID- 22360953
TI  - Management of 2nd-degree facial burns using the Versajet((r)) hydrosurgery system
      and xenograft: a prospective evaluation of 20 cases.
AB  - INTRODUCTION: There is no single therapeutic scheme for the management of
      intermediary 2nd-degree facial burns, which can cause problems because of their
      uncertain course. It is preferable to obtain optimal healing of the face in order
      to avoid functional or cosmetic sequelae. Some practitioners recommend early
      excision (first week) of these burns, whereas others prefer to wait and perform
      surgery later (after 2 weeks). The practice in our burns unit is early surgery
      (from the first week) associated with hydrosurgical excision and application of a
      biosynthetic dressing (xenograft). A prospective follow-up of 20 cases was
      carried out to evaluate the efficacy of our protocol. PATIENTS AND METHODS: The
      prospective evaluation was performed with follow-up at 2 weeks and 3, 6 and 12
      months. The patients included had intermediary 2nd-degree burns on at least 15%
      of the face and no life-threatening prognosis. The mean age in our series was
      40.5 years (16-72), the mean percentage of burn surface area was 27.75% and the
      mean percentage of facial burn was 60.75%. Early excision was performed (day 5
      10) using the Versajet((r)) system, which allows tangential water-dissection.
      Porcine xenograft (E-Z Derm((r))) was applied immediately afterwards. Patients
      whose healing process was not complete at 2 weeks were then scheduled to receive
      a thin autograft. Patients were followed up 2 weeks, 3, 6 and 12 months after
      discharge. RESULTS: Excision was performed at a mean 7.6 days, and mean initial
      healing time was 13.4 days. In three cases, a full-thickness skin graft was used,
      whereas healing occurred in the other patients without further grafts. Two
      patients had functional sequelae (ectropion) corrected later by repair surgery.
      The course of healing for the other patients proceeded normally. DISCUSSION:
      There is no consensus about the management of intermediate depth 2nd-degree
      facial burns. We chose to perform early surgery using the Versajet((r)) system,
      which allows fine, precise excision, leaving nearly all of the healthy tissue in
      place. The Versajet((r)) is particularly adapted to facial contours and is
      clearly more efficacious than the customary dermatomes. The use of a xenograft
      may augment facial healing while reducing the number of dressings and lessening
      patient discomfort. Our protocol provides the advantages of early management
      (limitation of functional sequelae, reduced hospitalization time), while avoiding
      too extensive or deep an excision through use of the Versajet((r)).

PMID- 22360954
TI  - Effects of Ligustrazine on pulmonary damage in rats following scald injury.
AB  - Organ protection is a routine therapy in severe burn/scald injuries, and damage
      mechanisms following early scald injury was not been fully elucidated. Our aim
      was to verify the beneficial effects of Ligustrazine on pulmonary damage
      associated with scald injury. Lewis rats were subjected to 30% total body surface
      area (TBSA) scald injury, and were randomly divided into a burn control (S group)
      and an Ligustrazine-treated group (L group). Lung malondialdehyde (MDA) and
      superoxide dismutase (SOD) levels were determined and the lungs were examined
      histologically with immunohistochemistry (IHC) as well for the MHC class I chain
      related antigen A (MICA) and Bcl-2 at 24, 48 and 72h after the injury. The
      expression of spleen HLA-DR was detected by immunohistochemistry analysis.
      Selectins and adhesion molecules in lungs and serum as well as pulmonary
      interleukins were also detected. The lung injury degree was represented as
      wet/dry (W/D) values and alveolar thickness. Ligustrazine decreased MDA levels
      and ameliorated the down-regulation of SOD activity. MICA was up-regulated after
      the scald, and this up-regulation was greatly diminished by Ligustrazine. Bcl-2
      was up-regulated after the scald, especially in the L group. The spleen HLA-DR
      expression demonstrated the immunoregulatory effects of Ligustrazine, which
      effectively protected pulmonary tissues from scald-induced injury. Our results
      demonstrated that pulmonay damage associated with autoimmunity and oxidant attack
      occurred after severe scald. Ligustrazine exhibits significant protective effects
      on these effects.

PMID- 22360955
TI  - Post-burn non-emergent hair in the male moustache area.

PMID- 22360956
TI  - Microvessel networks [corrected] pre-formed in artificial clinical grade dermal
      substitutes in vitro using cells from haematopoietic tissues.
AB  - Forming a microcirculation is critical for vascularisation of artificial skin
      substitutes. One strategy to improve speed of grafting is to pre-form
      microvascular networks in the substitute before applying to a wound. For clinical
      application, this requires sufficient functional endothelial cell numbers. In
      vitro endothelial colony forming cells (ECFCs) derived cells were expanded from
      cord and adult blood donations and co-cultured with human dermal fibroblasts or
      bone marrow mesenchymal stem/stromal cells to form microvascular networks in the
      presence or absence of dermal substitutes which are in clinical use. The number
      of endothelial cells generated ranged from 1.03*10(9) to 2.18*10(11) from 10
      adult blood donations and 1*10(12) to 1.76*10(13) from 6 cord blood units after
      50 days in culture. Two adult donations failed to generate ECFCs. Both cord and
      adult blood cells formed 2D microvascular networks in vitro, although there was a
      significant difference in the functional capacity of adult and cord blood ECFCs.
      While co-culture of the latter within dermal substitutes Matriderm or Integra
      demonstrated the formation of 3D microvascular networks penetrating 100MUm,
      enhanced expansion, while maintaining functional capacity, of adult blood cells
      is required for fully pre-vascularising the clinical grade acellular dermal
      substitutes used here prior to applying these to burns.

PMID- 22360957
TI  - MicroRNA profiling in denatured dermis of deep burn patients.
AB  - BACKGROUND: Denatured dermis is a part of the dermis in deep burn wound and has
      the ability to restore normal morphology and function. Skin grafting with the
      preservation of denatured dermis is a new kind of surgical procedure and has
      reported satisfactory clinical effects, such as lessened scar contracture and a
      better restoration of the appearance and function. However, the underlying
      mechanism of the recovery of denatured dermal function remains unclear. MicroRNAs
      (miRNAs) are a new class of regulatory noncoding single-stranded RNAs, which play
      a key role in normal development and physiology, as well as in disease
      development. This study analysed the profile of miRNAs in denatured dermis from
      patients and further investigated the possible roles of miRNAs played in the
      functional recovery of denatured dermis by prediction of the potential target
      genes of differentially expressed miRNAs. METHODS: The denatured dermis and
      paired normal skin were collected and analysed by miRNA array. The miRNA
      profiling results were validated by real-time reverse transcriptase polymerase
      chain reaction (RT-PCR), and bioinformatics' analysis was employed to further
      predict the miRNA targets. RESULTS: A total of 66 miRNAs were differentially
      expressed in denatured dermis compared with those in normal skin, among which 34
      were down-regulated while 32 are up-regulated. The most significantly up
      regulated miRNA was miR-663, and the most significantly down-regulated one was
      miR-203. Differentially expressed miRNAs were predicted to be related with
      several signalling pathways in wound healing. CONCLUSION: The differential miRNA
      expression identified in this study supplies experimental basis for further
      understanding the mechanisms of functional recovery of the denatured dermis.

PMID- 22360959
TI  - Suicidal burn in Hong Kong.
AB  - The aim of our study is to review our experience in the management of patients
      who sustained burns associated with suicidal attempts over a 10-year period. In
      particular, we look into the outcome and incidence of self-harm/suicide after
      discharge among the survivors. Thirty-one patients with median age 36 years,
      ranging from 10 to 74, were included. Twenty-three (74%) were males and eight
      (26%) were females. Nearly three quarters (74%) of our patients had a known
      history of psychiatric illness: 11 had known history of substance abuse; 3 of
      them had drug-induced psychosis; 6 had schizophrenia; 5 had depression; 4 had
      personality disorders; 1 had pathological gambling and another one had adjustment
      disorder. Relationship problems and work/financial difficulties were the
      commonest reason for the suicidal attempts. Self-inflicted flame burn was the
      most frequent (39%; 12 patients) method of burning. Six patients (19%) died. The
      remaining 25 patients healed and were discharged. Seventeen patients required ICU
      care. The median length of stay in ICU was 7 days. The overall median length of
      stay was 35 days. The median follow up time for those survived is 63 months. Only
      4 of these patients had further suicidal/parasuicidal attempts. Despite the high
      mortality, once these patients survived the initial injury, they are unlikely to
      commit suicide again. Thus, we believe that aggressive resuscitation should
      therefore be advocated for all suicidal burn patients.

PMID- 22360958
TI  - Three components of education in burn care: surgical education, inter
      professional education, and mentorship.
AB  - Education in burn care can be divided into three main components: surgical
      education, inter-professional education, e.g. critical care education and
      mentorship. To date these components have been used in varying degrees in most
      health institutions and to even lesser extent in burn care. The aim of this paper
      is to highlight each component and how these have been utilized in other fields
      to develop teams and foster education, and how they can be translated for burn
      teams. These ideas are not novel; however, this paper aims to shed light on how
      these concepts can be implemented in burn care, thus not only improving
      education, but also enabling recruitment and retention of health care providers
      in this field.

PMID- 22360960
TI  - Reconstruction of extensive upper extremity defects using pre-expanded oblique
      perforator-based paraumbilical flaps.
AB  - The pedicled paraumbilical flap is a reliable tissue transfer for hand and
      forearm reconstruction. However, its size, pedicle length and/or thickness limit
      its application in resurfacing of extensive defects of the upper limb. To conquer
      those limitations, this flap was pre-expanded for 10-24 weeks prior to transfer
      in 25 patients and used as a pedicle flap to cover upper extremity defects.
      Extensive defects of upper limb were reconstructed by the pre-expanded
      paraumbilical flaps. The flaps ranged in size from 10 cm * 8 cm to 30 cm * 14 cm.
      The donor sites were closed directly in all cases. All flaps survived, but two
      had partial flap necrosis due to venous congestion or infection. With pre
      transfer expansion, a large, well-perfused abdominal pedicle flap can be raised
      and transferred based on the paraumbilical perforators. This pre-expanded flap
      might be useful in the patients who have the extensive upper limb defects and
      sufficient time to allow tissue expansion.

PMID- 22360961
TI  - Cryopreserved human skin allografts: viability and delay of rejection in severely
      burned patients.

PMID- 22360962
TI  - Madecassoside suppresses migration of fibroblasts from keloids: involvement of
      p38 kinase and PI3K signaling pathways.
AB  - Keloid is a specific skin scar that expands beyond the boundaries of the original
      injury as it heals. The invasive nature of keloid and notable migratory activity
      of fibroblasts are a hallmark, which distinguishes keloids from other common
      scars. Madecassoside, a triterpenoid saponin occurring in Centella asiatica
      herbs, possesses unique pharmacological properties to enhance wound-healing and
      diminish keloid formation. However, the effects of madecassoside on the formation
      of keloid scars have been poorly understood. Here, we focused on the potential of
      madecassoside on the migration of keloid-derived fibroblasts (KFs) and its
      mechanism. Primary KF, originating from human earlobe keloids, were purified and
      cultured, and then treated with madecassoside (10, 30, and 100MUM). In both
      transwell migration assays and scratch-wound-closure assays, KF migration was
      considerably suppressed by madecassoside pretreatment. Furthermore, KFs treated
      with madecassoside showed decreased F-actin filaments, as revealed by fluorescein
      isothiocyanate (FITC)-phalloidin staining and confocal microscopy. By Western
      blot analysis, madecassoside was shown to remarkably attenuate the
      phosphorylation of cofilin, p38 MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT
      signaling, but only exhibited a minor effect on MMP-13 and little effect on
      ERK1/2 phosphorylation. It was concluded that madecassoside could be of great use
      in the treatment and/or prevention of hypertrophic scars and keloids.

PMID- 22360963
TI  - Molecular epidemiologic analysis of Staphylococcus aureus isolated from four burn
      centers.
AB  - Staphylococcus aureus has been a major cause of hospital-acquired infections.
      Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since 1980s as an
      epidemiologic problem in hospitals. This old pathogen brings a new challenge to
      all physicians and bacteriologists. Hence, effective measures of MRSA control are
      in critical need. S. aureus or MRSA is one of the leading causes of infection
      among burn centers, resulting in a number of poor outcomes and even death. The
      present study performed a molecular epidemiologic analysis of S. aureus isolated
      from four burn centers in the southeast of China. A total of 85 isolates were
      collected, and molecular characters were determined for further investigation. In
      this study, the prevalent clone of MRSA among four burn centers was found to be
      SCCmec III (spa-type t030, agr I), which is resistant to 4 kinds of
      antimicrobials including erythromycin, clindamycin, kanamycin and mupirocin.
      Discrepancy between mecA detection and conventional tests used for MRSA
      identification was observed unintentionally. Our data demonstrated that the
      overall prevalence rate of MRSA was 55.3%, and drugs such as
      sulfamethoxazole/trimethoprim, linezolid and fusidic acid are efficient
      antibiotic options for treating S. aureus or MRSA infections among four burn
      centers studied in present investigation.

PMID- 22360964
TI  - Resurfacing large skin defects of the face and neck with expanded subclavicular
      flaps pedicled by the thoracic branch of the supraclavicular artery.
AB  - BACKGROUND: Supraclavicular flaps had been widely used as pedicled flaps to
      reconstruct face and neck defects. However, the size of this traditional flap was
      limited even after expansion. In this study, we present a flap pedicled by the
      thoracic branch of supraclavicular artery (TBSA). The flap is located at the
      subclavicular region, and has the advantage of large dimension, matching colour
      and thin thickness. METHODS: In this series, 24 patients with ages ranging
      between 3 and 49 years (30 flaps with six patients in bilateral fashion) were
      treated in the authors' institution. RESULTS: The maximum size of the flap was 25
      cm * 25 cm, whereas the minimum size was 15 cm * 10 cm. The average size of the
      flaps was 241.1 +/- 95.7 cm(2). Twenty-six flaps (86.7%) survived completely.
      Total flap loss was seen in one patient (3.3%) and was treated with reverse
      harvesting skin graft. Partial flap necrosis occurred in three flaps (10.0%).
      Through a mean time of 10-month follow-up, the colour and the texture of the
      flaps matched with the recipient area. No conspicuous flap contracture was
      observed. CONCLUSION: This expanded subclavicular flap pedicled by the TBSA has
      proved to be a promising method with satisfactory outcome and high success rate.

PMID- 22360965
TI  - How should teaching of undergraduates in clinical pharmacology and therapeutics
      be delivered and assessed?
AB  - Clinical pharmacology and therapeutics is the academic discipline that informs
      rational prescribing of medicines. There is accumulating evidence that a
      significant minority of prescriptions in the UK National Health Service contain
      errors. This comes at a time when the approach to and success of undergraduate
      education in this area has been called into question. Various stakeholders are
      now in agreement that this challenging area of undergraduate education needs to
      be strengthened. The principles that should form the basis of future educational
      strategy include greater visibility of clinical pharmacology and therapeutics in
      the curriculum, clear learning outcomes that are consistent with national
      guidance, strong and enthusiastic leadership, a student formulary, opportunities
      to practice prescribing, a robust assessment of prescribing competencies and
      external quality control. Important new developments in the UK are Prescribe, a
      repository of e-learning materials to support education in clinical pharmacology
      and prescribing, and the Prescribing Skills Assessment, a national online
      assessment designed to allow medical students to demonstrate that they have
      achieved the core competencies required to begin postgraduate training.

PMID- 22360966
TI  - Identification and phenology of Hyalesthes obsoletus (Hemiptera: Auchenorrhyncha:
      Cixiidae) nymphal instars.
AB  - Urtica dioica and Convolvulus arvensis are the main host plants of Hyalesthes
      obsoletus and play an important role in the epidemiology of Bois noir of
      grapevines. The earliest survey, which was carried out to compare the phenology
      of nymphal instars on U. dioica and C. arvensis, had highlighted some problems in
      the identification of the instars. Therefore, the correct identification of
      nymphs to species and instar level became a preliminary aim of this research.
      Adults and nymphs attributable to H. obsoletus were collected during 2008-2010 in
      three flatland vineyard habitats of northern Italy on U. dioica, C. arvensis and
      Artemisia verlotorum. Nymphs and morphologically identified adults of H.
      obsoletus were submitted to molecular identification. Morphometric and
      morphological studies were carried out on nymphs collected in the field or
      obtained in laboratory rearings. Molecular methods not only confirmed the
      identity of adults, but also allowed the assignment of the nymphs to this
      species. Morphometric and morphological characteristics (e.g. body and head
      thoracic lengths, number of thoracic pits) showed the existence of five nymphal
      instars. Morphometric differences between newly hatched and older first-instar
      nymphs were observed. A key to distinguish the five instars was proposed. Evident
      differences between H. obsoletus nymphs studied here and elsewhere were
      identified. According to differences in adult-flight period, an earlier phenology
      of nymphs on C. arvensis than on U. dioica was observed. In particular, the
      typical overwintering instar was the second on U. dioica and the third on C.
      arvensis. 

PMID- 22360967
TI  - The proto-oncogene Ret is required for male foetal germ cell survival.
AB  - The spermatogenic and oogenic lineages originate from bipotential primordial germ
      cells in response to signalling in the foetal testis or ovary, respectively. The
      signals required for male germ cell commitment and their entry into mitotic
      arrest remain largely unknown. Recent data show that the ligand GDNF is up
      regulated in the foetal testis indicating that it may be involved in male germ
      cell development. In this study genetic analysis of GDNF-RET signalling shows
      that RET is required for germ cell survival. Affected germ cells in Ret-/- mice
      lose expression of key germ cell markers, abnormally express cell cycle markers
      and undergo apoptosis. Surprisingly, a similar phenotype was not detected in Gdnf
      /- mice indicating that either redundancy with a Gdnf related gene might
      compensate for its loss, or that RET operates in a GDNF independent manner in
      mouse foetal germ cells. Either way, this study identifies the proto-oncogene RET
      as a novel component of the foetal male germ cell development pathway.

PMID- 22360968
TI  - F3/Contactin acts as a modulator of neurogenesis during cerebral cortex
      development.
AB  - The expression of the cell recognition molecule F3/Contactin (CNTN1) is generally
      associated with the functions of post-mitotic neurons. In the embryonic cortex,
      however, we find it expressed by proliferating ventricular zone (VZ) precursors.
      In contrast to previous findings in the developing cerebellum, F3/Contactin
      transgenic overexpression in the early cortical VZ promotes proliferation and
      expands the precursor pool at the expense of neurogenesis. At later stages, when
      F3/Contactin levels subside, however, neurogenesis resumes, suggesting that
      F3/Contactin expression in the VZ is inversely related to neurogenesis and plays
      a role in a feedback control mechanism, regulating the orderly progression of
      cortical development. The modified F3/Contactin profile therefore results in
      delayed corticogenesis, as judged by downregulation in upper and lower layer
      marker expression and by BrdU birth dating, indicating that, in this transgenic
      model, increased F3/Contactin levels counteract neuronal precursor commitment.
      These effects also occur in primary cultures and are reproduced by addition of an
      F3/Fc fusion protein to wild type cultures. Together, these data indicate a
      completely novel function for F3/Contactin. Parallel changes in the generation of
      the Notch Intracellular Domain and in the expression of the Hes-1 transcription
      factor indicate that activation of the Notch pathway plays a role in this
      phenotype, consistent with previous in vitro reports that F3/Contactin is a
      Notch1 ligand.

PMID- 22360969
TI  - Broad reach and targeted recruitment using Facebook for an online survey of young
      adult substance use.
AB  - BACKGROUND: Studies of tobacco use and other health behaviors have reported great
      challenges in recruiting young adults. Social media is widely used by young
      adults in the United States and represents a potentially fast, affordable method
      of recruiting study participants for survey research. OBJECTIVE: The present
      study examined Facebook as a mechanism to reach and survey young adults about
      tobacco and other substance use. METHODS: Participants were cigarette users, age
      18-25 years old, living throughout the United States and recruited through
      Facebook to complete a survey about tobacco and other substance use. Paid
      advertising using Facebook's Ad program over 13 months from 2010 Feb 28 to 2011
      Apr 4 targeted by age (18-25), location (United States or California), language
      (English), and tobacco- and/or marijuana-related keywords. Facebook approved all
      ads. RESULTS: The campaign used 20 ads, which generated 28,683,151 impressions,
      yielding 14,808 clicks (0.7% of targeted Facebook members), at an overall cost of
      $6,628.24. The average cost per click on an ad was $0.45. The success of
      individual ads varied widely. There was a rise in both clicks and impressions as
      the campaign grew. However, the peak for clicks was 3 months before the peak for
      ad impressions. Of the 69,937,080 accounts for those age 18-25 in the United
      States, Facebook estimated that 2.8% (n = 1,980,240) were reached through tobacco
      and marijuana keywords. Our campaign yielded 5237 signed consents (35.4% of
      clicks), of which 3093 (59%) met criteria, and 1548 (50% of those who met
      criteria) completed the survey. The final cost per valid completed survey was
      $4.28. The majority of completed surveys came from whites (69%) and males (72%).
      The sample averaged 8.9 cigarettes per day (SD 7.5), 3.8 years of smoking (SD
      2.9), with a median of 1 lifetime quit attempts; 48% did not intend to quit
      smoking in the next 6 months. CONCLUSIONS: Despite wide variety in the success of
      individual ads and potential concerns about sample representativeness, Facebook
      was a useful, cost-effective recruitment source for young-adult smokers to
      complete a survey about the use of tobacco and other substances. The current
      findings support Facebook as a viable recruitment option for assessment of health
      behavior in young adults.

PMID- 22360970
TI  - Differential effects of dietary supplements on metabolomic profile of smokers
      versus non-smokers.
AB  - BACKGROUND: Cigarette smoking is well-known to associate with accelerated skin
      aging as well as cardiovascular disease and lung cancer, in large part due to
      oxidative stress. Because metabolites are downstream of genetic variation, as
      well as transcriptional changes and post-translational modifications of proteins,
      they are the most proximal reporters of disease states or reversal of disease
      states. METHODS: In this study, we explore the potential effects of commonly
      available oral supplements (containing antioxidants, vitamins and omega-3 fatty
      acids) on the metabolomes of smokers (n = 11) compared to non-smokers (n = 17).
      At baseline and after 12 weeks of supplementation, metabolomic analysis was
      performed on serum by liquid and gas chromatography with mass spectroscopy (LC-MS
      and GC-MS). Furthermore, clinical parameters of skin aging, including cutometry
      as assessed by three dermatologist raters blinded to subjects' age and smoking
      status, were measured. RESULTS: Long-chain fatty acids, including palmitate and
      oleate, decreased in smokers by 0.76-fold (P = 0.0045) and 0.72-fold (P =
      0.0112), respectively. These changes were not observed in non-smokers.
      Furthermore, age and smoking status showed increased glow (P = 0.004) and a
      decrease in fine wrinkling (P = 0.038). Cutometry showed an increase in skin
      elasticity in smokers (P = 0.049) but not in non-smokers. Complexion analysis
      software (VISIA) revealed decreases in the number of ultraviolet spots (P =
      0.031), and cutometry showed increased elasticity (P = 0.05) in smokers but not
      non-smokers. CONCLUSIONS: Additional future work may shed light on the specific
      mechanisms by which long-chain fatty acids can lead to increased glow, improved
      elasticity measures and decreased fine wrinkling in smokers' skin. Our study
      provides a novel, medicine-focused application of available metabolomic
      technology to identify changes in sera of human subjects with oxidative stress,
      and suggests that oral supplementation (in particular, commonly available
      antioxidants, vitamins and omega-3 fatty acids) affects these individuals in a
      way that is unique (compared to non-smokers) on a broad level.

PMID- 22360972
TI  - Lymphatic malformations of the head and neck-current concepts in management.
AB  - Lymphatic malformations of the head and neck, also known as lymphangiomas or
      cystic hygromas, are a diverse group of lesions. They can be small and
      superficial or large and extensive, and management can be a challenge. Surgically
      they can be difficult to remove completely because of their poorly defined
      borders and the potential for damaging neighbouring structures. We review the
      dilemmas posed in diagnosis and treatment, and discuss the contemporary
      management of these interesting entities including sclerotherapy, which is
      gaining popularity.

PMID- 22360971
TI  - The expression and activity of beta-catenin in the thalamus and its projections
      to the cerebral cortex in the mouse embryo.
AB  - BACKGROUND: The mammalian thalamus relays sensory information from the periphery
      to the cerebral cortex for cognitive processing via the thalamocortical tract.
      The thalamocortical tract forms during embryonic development controlled by
      mechanisms that are not fully understood. beta-catenin is a nuclear and cytosolic
      protein that transduces signals from secreted signaling molecules to regulate
      both cell motility via the cytoskeleton and gene expression in the nucleus. In
      this study we tested whether beta-catenin is likely to play a role in
      thalamocortical connectivity by examining its expression and activity in
      developing thalamic neurons and their axons. RESULTS: At embryonic day (E)15.5,
      the time when thalamocortical axonal projections are forming, we found that the
      thalamus is a site of particularly high beta-catenin mRNA and protein expression.
      As well as being expressed at high levels in thalamic cell bodies, beta-catenin
      protein is enriched in the axons and growth cones of thalamic axons and its
      growth cone concentration is sensitive to Netrin-1. Using mice carrying the beta
      catenin reporter BAT-gal we find high levels of reporter activity in the
      thalamus. Further, Netrin-1 induces BAT-gal reporter expression and upregulates
      levels of endogenous transcripts encoding beta-actin and L1 proteins in cultured
      thalamic cells. We found that beta-catenin mRNA is enriched in thalamic axons and
      its 3'UTR is phylogenetically conserved and is able to direct heterologous mRNAs
      along the thalamic axon, where they can be translated. CONCLUSION: We provide
      evidence that beta-catenin protein is likely to be an important player in
      thalamocortcial development. It is abundant both in the nucleus and in the growth
      cones of post-mitotic thalamic cells during the development of thalamocortical
      connectivity and beta-catenin mRNA is targeted to thalamic axons and growth cones
      where it could potentially be translated. beta-catenin is involved in transducing
      the Netrin-1 signal to thalamic cells suggesting a mechanism by which Netrin-1
      guides thalamocortical development.

PMID- 22360973
TI  - Reducing the risk of retained throat packs after surgery.

PMID- 22360974
TI  - Impact of tactile dysfunction on upper-limb motor performance in children with
      unilateral cerebral palsy.
AB  - OBJECTIVE: To determine the relationship between tactile function and upper-limb
      function in children with unilateral cerebral palsy (CP). DESIGN: Cross-sectional
      study. SETTING: Assessments were performed in community or hospital venues or in
      participants' homes. PARTICIPANTS: Recruitment information was sent to 253
      possible participants with unilateral CP (aged 8-18 y), and N=52 participated
      (median age [interquartile range], 12 y [9-14 y]; Gross Motor Functional
      Classification System level I=34; II=18; Manual Abilities Classification Scale
      level I=36; II=16). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Tactile
      assessment included 1 test of registration, 5 tests for spatial perception, and 1
      test for texture perception. Upper-limb motor function was assessed using 2
      unimanual tests, the Melbourne Unilateral Upper Limb Assessment (MUUL) and Jebsen
      Taylor Test of Hand Function (JTTHF), and 1 bimanual test, the Assisting Hand
      Assessment (AHA). RESULTS: Tactile registration and all tests of spatial
      perception were moderately related to the MUUL, JTTHF, and AHA (P<.001). Texture
      perception was not related to upper-limb motor function. Regression analysis
      showed that single point localization, a unilateral tactile spatial perception
      test, contributed most strongly to unimanual capacity (29% explained variance in
      MUUL and 26% explained variance in JTTHF), whereas double simultaneous, a
      bilateral tactile spatial perception test, contributed most strongly to bimanual
      performance (33% for the AHA). CONCLUSIONS: Spatial tactile deficits account for
      approximately 30% of the variance in upper-limb motor function in children with
      unilateral CP. This emphasizes the need for routine tactile assessment and
      targeted treatment of tactile spatial deficits in this population.

PMID- 22360975
TI  - Most essential wheeled mobility skills for daily life: an international survey
      among paralympic wheelchair athletes with spinal cord injury.
AB  - OBJECTIVES: To create a hierarchical list of the most essential wheeled mobility
      (WM) skills for everyday life of wheelchair users with a spinal cord injury
      (SCI), and to compare perceptions of WM gained during and after clinical
      rehabilitation. DESIGN: Cross-sectional study using survey questionnaires.
      SETTING: The Beijing Paralympic games, at the international zone of the Olympic
      village and in different sports venues. PARTICIPANTS: A sample of men (N=49) and
      women (N=30) elite manual wheelchair user athletes with SCI (paraplegia, n=64;
      tetraplegia, n=15). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: A survey
      with 24 predefined skills was distributed during the Beijing Paralympic games.
      Respondents were asked to rate the essentiality of each skill (1, not essential;
      5, extremely essential); to state where, when, and with whom they have learned to
      perform each skill; and to mark the level of WM, which they gained during and
      after clinical rehabilitation, on 3 different WM visual analog scales (scores 1
      10). RESULTS: Rated as the most essential skill was transfer into and out of a
      car (mean +/- SD, 4.7+/-0.7). Rated as the least essential skill was the 1-handed
      wheelie (mean +/- SD, 1.9+/-1.3). Of the respondents, 57% have learned the most
      essential skills in clinical rehabilitation, while 40% claimed to have learned
      those skills afterward in a community setting. Three percent have never learned
      to perform the most essential skills. Of the very essential skills, 40% were self
      taught. Mean score +/- SD for the extent to which WM skills were gained in
      rehabilitation was 5.4+/-2.5. CONCLUSIONS: The main survey outcome is a sorted
      list of WM skills according to their essentiality for daily life of hand-rim
      wheelchair users with SCI. It is recommended to incorporate the skills that were
      graded as very essential and extremely essential during inpatient rehabilitation
      and in postrehabilitation WM workshops.

PMID- 22360976
TI  - Functional motor preservation below the level of injury in subjects with American
      Spinal Injury Association Impairment Scale grade A spinal cord injuries.
AB  - OBJECTIVE: To assess how frequently subjects with spinal cord injuries (SCIs)
      classified as American Spinal Injury Association Impairment Scale (AIS) grade A
      have substantial preserved motor function below the neurologic level of injury,
      despite having no preserved sensory or motor function at the S4-5 spinal cord
      segment. DESIGN: Analysis of the European Multicenter Study about Spinal Cord
      Injury database to determine how frequently subjects assessed as AIS A would have
      been AIS D based on motor scores alone (ie, had scores of >=3 in at least half of
      the International Standards for Neurological Classification of Spinal Cord Injury
      [ISNCSCI] key muscles below the neurologic level of injury, despite having no
      sacral sparing). SETTING: Eighteen European centers. PARTICIPANTS: Individuals
      with traumatic SCI at any level (total of 2557 assessments). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: ISNCSCI assessments. RESULTS: Over the first
      year after SCI (with assessments at approximately 1, 4, 12, 24, and 48wk) and for
      all rostrocaudal levels of injury, only 3.2% of AIS A assessments were found to
      meet the AIS D motor score criteria. The percentage was highest for lumbar
      (16.3%) and lower thoracic (4.4%) SCI. No trends were observed across time
      points. CONCLUSIONS: These results suggest that the low frequency of individuals
      with an AIS A classification and high levels of motor function are not a
      significant concern in subject recruitment for clinical trials, unless the level
      of SCI is within the lumbar cord.

PMID- 22360977
TI  - Transcription factor E3, a major regulator of mast cell-mediated allergic
      response.
AB  - BACKGROUND: Microphthalmia transcription factor, an MiT transcription family
      member closely related to transcription factor E3 (TFE3), is essential for mast
      cell development and survival. TFE3 was previously reported to play a role in the
      functions of B and T cells; however, its role in mast cells has not yet been
      explored. OBJECTIVE: We sought to explore the role played by TFE3 in mast cell
      function. METHODS: Mast cell numbers were evaluated by using toluidine blue
      staining. FACS analysis was used to determine percentages of Kit and FcepsilonRI
      double-positive cells in the peritoneum of wild-type (WT) and TFE3 knockout
      (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in
      immunologically activated cultured mast cells derived from either knockout or WT
      mice. In vivo plasma histamine levels were measured after immunologic triggering
      of these mice. RESULTS: No significant differences in mast cell numbers between
      WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However,
      TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and
      FcepsilonRI(+) peritoneal and cultured mast cells. Surface expression levels of
      FcepsilonRI in TFE3(-/-) peritoneal mast cells was significantly lower than in
      control cells. Cultured mast cells derived from TFE3(-/-) mice showed a marked
      decrease in degranulation and mediator secretion. In vivo experiments showed that
      the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was
      substantially less than that seen in WT mice. CONCLUSION: TFE3 is a novel
      regulator of mast cell functions and as such could emerge as a new target for the
      manipulation of allergic diseases.

PMID- 22360978
TI  - Filaggrin mutations increase the risk for persistent dry skin and eczema
      independent of sensitization.

PMID- 22360980
TI  - The nanoscale phase distinguishing of PCL-PB-PCL blended in epoxy resin by
      tapping mode atomic force microscopy.
AB  - In this work, we investigated the bulk phase distinguishing of the poly(epsilon
      caprolactone)-polybutadiene-poly(epsilon-caprolactone) (PCL-PB-PCL) triblock
      copolymer blended in epoxy resin by tapping mode atomic force microscopy (TM
      AFM). We found that at a set-point amplitude ratio (rsp) less than or equal to
      0.85, a clear phase contrast could be obtained using a probe with a force
      constant of 40 N/m. When rsp was decreased to 0.1 or less, the measured size of
      the PB-rich domain relatively shrank; however, the height images of the PB-rich
      domain would take reverse (translating from the original light to dark) at rsp =
      0.85. Force-probe measurements were carried out on the phase-separated regions by
      TM-AFM. According to the phase shift angle vs. rsp curve, it could be concluded
      that the different force exerting on the epoxy matrix or on the PB-rich domain
      might result in the height and phase image reversion. Furthermore, the
      indentation depth vs. rsp plot showed that with large tapping force (lower rsp),
      the indentation depth for the PB-rich domain was nearly identical for the epoxy
      resin matrix.

PMID- 22360979
TI  - Increased serum CRH levels with decreased skin CRHR-1 gene expression in
      psoriasis and atopic dermatitis.

PMID- 22360981
TI  - Robotic transaxillary thyroidectomy: an examination of the first one hundred
      cases.
AB  - BACKGROUND: The influence of minimally invasive options has led to the
      application of new evolving techniques in thyroid surgery to eliminate visible
      neck scars. Here, we describe one author's experience with transaxillary robotic
      thyroidectomy and examine the effect of experience on determining the learning
      curve and improvements over time in operative performance. STUDY DESIGN: With IRB
      approval, a prospective analysis of our surgical experience was performed. All
      patients underwent robotic transaxillary thyroidectomy by a single surgeon
      between September 2009 and June 2011. Principal outcomes measures included length
      of hospital stay, incidence of complications, and effect of obesity on outcomes.
      RESULTS: One hundred consecutive operations were performed on 91 patients. Sixty
      nine hemithyroidectomy, 22 total or near-total thyroidectomy, and 9 completion
      thyroidectomy procedures were performed. Of patients who underwent
      hemithyroidectomy, 21.7% were discharged within 4 hours; the remaining patients
      were discharged within 23 hours. Mean operative time for hemithyroidectomy was
      108.1 +/- 60.5 minutes, and for total or near-total thyroidectomy, mean operative
      time was 118.1 +/- 51.3 minutes. Mean robot docking time was 9.1 +/- 2.2 minutes
      for all cases. Obesity contributed to prolonged total operative time. Improvement
      in the length of time to perform components of the procedure was noted after 45
      cases. Two cases required conversion to a cervical approach. There were no
      instances of permanent vocal cord palsy on postoperative laryngoscopy.
      CONCLUSIONS: Here we report the largest experience of robotic gasless thyroid
      surgery in the United States. This novel technique provides excellent cosmetic
      results and can be performed as an outpatient procedure in selected group of
      patients. It is feasible and safe, however, has a lengthy learning curve.

PMID- 22360983
TI  - Predictable closure of the abdominoperineal resection defect: a novel two-team
      approach.
AB  - BACKGROUND: Primary closure of the perineum at the time of abdominoperineal
      resection (APR) is seldom successful. Several factors are known to adversely
      affect healing, including neoadjuvant chemoradiation, tension, contamination, and
      fluid collection. This study evaluates a 2-team approach for resection and
      routine perineal closure in a single stage. STUDY DESIGN: After tumor resection,
      the abdominal and perineal closures are performed simultaneously by 2 separate
      teams. A competent closure of the perineal defect is achieved with bilateral V-to
      Y inferior gluteal artery perforator fasciocutaneous flaps (BIGAP) mobilizing
      buttock skin, fat, and gluteal muscle fascia for inset into the defect. No muscle
      is elevated with the flaps and no attempt is made to obliterate the deepest
      aspects of the pelvic defect. RESULTS: Beginning in August 2010, 18 consecutive
      patients who underwent APR for distal rectal (n = 14) and anal carcinoma (n = 4)
      were included in the study. All patients had received neoadjuvant chemoradiation
      therapy. Primary healing was achieved in 16 of 18 patients with a completely
      tension-free closure. One patient required debridement and secondary closure.
      Another patient had an unresectable tumor, which invaded the flap closure. Minor
      healing problems were seen in 7 patients. CONCLUSIONS: BIGAP flaps provide
      sufficient tissue to predictably provide primary closure of the perineal defect.
      Perineal wound healing morbidity is dramatically reduced compared with primary
      simple closure of this defect. Early results indicate that this method of
      perineal closure offers a straightforward and predictable method that is
      comparable in efficacy to other methods using pedicled flaps for perineal
      closure.

PMID- 22360982
TI  - Ex vivo interleukin-12-priming during CD8(+) T cell activation dramatically
      improves adoptive T cell transfer antitumor efficacy in a lymphodepleted host.
AB  - BACKGROUND: Clinical application of adoptive T cell therapy has been hindered by
      an inability to generate adequate numbers of nontolerized, functionally active,
      tumor-specific T cells, which can persist in vivo. In order to address this, we
      evaluated the impact of interleukin (IL)-12 signaling during tumor-specific
      CD8(+) T cell priming in terms of persistence and antitumor efficacy using an
      established B16 melanoma tumor adoptive therapy model. STUDY DESIGN: B6 mice were
      injected subcutaneously with B16 melanoma tumor cells. On day 12 of tumor growth,
      mice were preconditioned with cyclophosphamide (4mg dose, intraperitoneally), and
      1 day later were treated by adoptive transfer of tumor-specific pmel-1 CD8(+) T
      cells primed ex vivo 3 days earlier with both IL-12 and antigen (hGP100(25-33)
      peptide) or antigen only. Tumors were measured biweekly, and infused donor T
      cells were analyzed for persistence, localization to the tumor, phenotype, and
      effector function. RESULTS: Adoptive transfer of tumor-specific CD8(+) T cells
      primed with IL-12 was significantly more effective in reducing tumor burden in
      mice preconditioned with cyclophosphamide compared with transfer of T cells
      primed without IL-12. This enhanced antitumor response was associated with
      increased frequencies of infused T cells in the periphery and tumor as well as
      elevated expression of effector molecules including granzyme B and interferon
      gamma (IFNgamma). CONCLUSIONS: Our findings demonstrate that ex vivo priming of
      tumor-specific CD8(+) T cells with IL-12 dramatically improves their in vivo
      persistence and therapeutic ability on transfer to tumor-bearing mice. These
      findings can be directly applied as novel clinical trial strategies.

PMID- 22360984
TI  - Fabrication of biomimetic high performance antireflective and antifogging film by
      spin-coating.
AB  - In this paper, we report a facile way to fabricate biomimetic high performance
      optical hybrid films with excellent antireflective and antifogging properties by
      one-step spin-coating the mixture of mesoporous SiO(2) particles and SiO(2) sol.
      The production process of the films is easy, low-cost, and time-efficient.
      Mesoporous SiO(2) particles containing surfactants disperse in SiO(2) sol stably
      without any chemical modification, which decrease the effective refractive index
      and increase the transmittance of the films. In addition, such films possess
      superhydrophilic properties and exhibit high performance antifogging properties.
      Due to the good film forming performance of SiO(2) sol, mesoporous SiO(2)
      particles are embedded in the films and impart the films high mechanical
      stability and durability. The surface morphology of the films can maintain well
      after repeated friction, and the performances of antireflective and antifogging
      also do not change as well.

PMID- 22360985
TI  - Correlation of macroscopic aggregation behavior and microscopic adhesion
      properties of bacteria strains using a dimensionless Tabor's parameter.
AB  - Macroscopic adhesion-aggregation, floc formation, and subsequent transportation
      of microorganisms in porous media are closely related to the microscopic behavior
      and properties of individual cells. The classical Tabor's parameter in colloidal
      science is modified to correlate the macroscopic aggregation and microscopic
      adhesion properties of microorganisms. Seven bacterial strains relevant to
      wastewater treatment and bioremediation were characterized in terms of their
      macroscopic aggregation index (AI) using an optical method, and their microscopic
      coupled adhesion and deformation properties using atomic force microscopy (AFM).
      Single cells were indented to measure the range and magnitude of the repulsive
      attractive intersurface forces, elastic modulus, thickness and density of the
      cellular surface substances (CSS). The strong correlation suggests that cost and
      time effective microscopic AFM characterization is capable of making reliable
      prediction of macroscopic behavior.

PMID- 22360986
TI  - Good publishing practice.

PMID- 22360987
TI  - Systematic reviews identify important methodological flaws in stroke
      rehabilitation therapy primary studies: review of reviews.
AB  - OBJECTIVE: A "review of reviews" was undertaken to assess methodological issues
      in studies evaluating nondrug rehabilitation interventions in stroke patients.
      STUDY DESIGN AND SETTING: MEDLINE, CINAHL, PsycINFO, and the Cochrane Database of
      Systematic Reviews were searched from January 2000 to January 2008 within the
      stroke rehabilitation setting. Electronic searches were supplemented by reviews
      of reference lists and citations identified by experts. Eligible studies were
      systematic reviews; excluded citations were narrative reviews or reviews of
      reviews. Review characteristics and criteria for assessing methodological quality
      of primary studies within them were extracted. RESULTS: The search yielded 949
      English-language citations. We included a final set of 38 systematic reviews.
      Cochrane reviews, which have a standardized methodology, were generally of higher
      methodological quality than non-Cochrane reviews. Most systematic reviews used
      standardized quality assessment criteria for primary studies, but not all were
      comprehensive. Reviews showed that primary studies had problems with
      randomization, allocation concealment, and blinding. Baseline comparability,
      adverse events, and co-intervention or contamination were not consistently
      assessed. Blinding of patients and providers was often not feasible and was not
      evaluated as a source of bias. CONCLUSIONS: The eligible systematic reviews
      identified important methodological flaws in the evaluated primary studies,
      suggesting the need for improvement of research methods and reporting.

PMID- 22360988
TI  - Studies of stroke rehabilitation therapies should report blinding and rationalize
      use of outcome measurement instruments.
AB  - OBJECTIVE: To review the reporting of key design features in studies of stroke
      rehabilitation therapies. STUDY DESIGN AND SETTING: We used purposive sampling to
      examine English-language, human-subject, comparative studies focusing on stroke
      rehabilitation therapy provided the effect of therapy was evaluated in at least
      one of the following six outcome domains: ambulation, cognition, quality of life,
      daily activities, dysphagia, or communication. We searched MEDLINE(r), CINAHL(r),
      PsycINFO(r), and the Cochrane Database of Systematic Reviews (date range: January
      2000 through late-January 2008) and extracted data from included studies using
      standardized forms. We depicted the extracted data in tables and summarized the
      findings qualitatively in the text. RESULTS: We retrieved 1,674 citations in the
      literature search and extracted data from 99 studies. Authors' reporting of key
      design features in stroke rehabilitation studies was lacking in four areas, that
      is, the background of persons delivering therapy, timing of therapy, subjects'
      receipt of prior or concomitant treatment, and psychometric properties of outcome
      measurement instruments. CONCLUSIONS: Except for four areas, reporting of key
      design features in studies of stroke rehabilitation therapies was quite
      comprehensive. Researchers should pay particular attention to reporting blinding,
      and they should rationalize the number of outcome measurement instruments used in
      their studies.

PMID- 22360989
TI  - Development of a patient-reported outcome measure for the foot affected by
      rheumatoid arthritis.
AB  - OBJECTIVE: To develop an idiographic and nomothetic patient-reported outcome
      measure (PROM) for the assessment and evaluation of patients with feet affected
      by rheumatoid arthritis (RA). STUDY DESIGN AND SETTING: The development of the
      Salford Rheumatoid Arthritis Foot Evaluation (SAFE) Instrument PROM was divided
      into four stages: establishment of the PROM's conceptual basis and content
      generation, following a descriptive phenomenological study; clinimetric
      instrument development; instrument pretesting, involving expert reviews and
      cognitive interviews; and demonstration of instrument measurement properties,
      including convergent validity and test-retest reliability of the nomothetic
      scale. RESULTS: A total of 123 items were initially generated for the SAFE, with
      25 of them clinimetrically selected for nomothetic scale (SAFE-Part A) and 80
      items initially included in the idiographic scale (SAFE-Part B). The pretesting
      strategy proved effective for improving and refining the SAFE, with the final
      draft consisting of 19 items in Part A and 42 items in Part B. The SAFE-Part A
      has strong evidence for convergent validity and test-retest reliability.
      CONCLUSION: The SAFE features a nomothetic and idiographic assessment strategy
      that, with further development, will prove to be a valuable tool for clinicians
      involved in managing the foot health problems associated with RA.

PMID- 22360990
TI  - The development of a postoperative morbidity score to assess total morbidity
      burden after cardiac surgery.
AB  - OBJECTIVE: To develop a tool for identifying and quantifying morbidity following
      cardiac surgery (cardiac postoperative morbidity score [C-POMS]). STUDY DESIGN
      AND SETTING: Morbidity was prospectively assessed in 450 cardiac surgery patients
      on postoperative days 1, 3, 5, 8, and 15 using POMS criteria (nine postoperative
      morbidity domains in general surgical patients) and cardiac-specific variables
      (from expert panel). Other morbidities were noted as free text and included if
      prevalence was more than 5%, missingness less than 5%, and mean expert-rated
      severity-importance index score more than 8. Construct validity was assessed by
      expert panel review, Cronbach's alpha (internal consistency), and linear
      regression (predictive ability of C-POMS for length of stay [LOS]). RESULTS: A 13
      domain model was derived. Internal consistency (>0.7) on D3-D15 permits use as a
      summative score of total morbidity burden. Mean C-POMS scores were 3.4 (D3), 2.6
      (D5), 3.4 (D8), and 3.8 (D15). Patient LOS was 4.6 days (P=0.012), 5.3 days
      (P=0.001), and 7.6 days (P=0.135) longer in patients with C-POMS-defined
      morbidity on D3, D5, D8, and D15, respectively, than in those without. For every
      unit increase in C-POMS summary score, subsequent LOS increased by 1.7 (D3), 2.2
      (D5), 4.5 (D8), and 6.2 (D15) days (all P=0.000). CONCLUSION: C-POMS is the first
      validated tool for identifying total morbidity burden after cardiac surgery.
      However, further external validation is warranted.

PMID- 22360991
TI  - The "Spirit 8" successfully captured spiritual well-being in African palliative
      care: factor and Rasch analysis.
AB  - OBJECTIVE: To describe the dimensionality of a measure of spiritual well-being
      (SWB) (the "Spirit 8") in palliative care (PC) patients in South Africa and
      Uganda, and to determine SWB in this population. STUDY DESIGN AND SETTING: A
      cross-sectional survey was conducted using the Missoula Vitas Quality of Life
      Index (MVQOLI). Translated questionnaires were administered to consecutively
      recruited patients. Factor analysis and Rasch analysis were used to examine the
      dimensionality of eight items from the Well-being and Transcendent subscales. The
      resulting measure (the "Spirit 8") was used to determine levels of SWB. RESULTS:
      Two hundred eighty-five patients recruited; mean age 40.1; 197 (69.1%) female;
      primary diagnosis HIV (80.7%), cancer (17.9%). Internal consistency of the eight
      item scale was alpha=0.73; Well-being factor alpha=0.69, Transcendence factor
      alpha=0.68. Rasch analysis suggested unidimensionality. Mean SWB score was 26.01
      (standard deviation 5.68). Spiritual distress was present in 21.4-57.9%.
      Attending the Ugandan service, HIV and younger age were associated with poorer
      SWB scores. CONCLUSION: The Spirit 8 is a brief, psychometrically robust,
      unidimensional measure of SWB for use in South African and Ugandan PC research.
      Further research testing the Spirit 8 and examining the SWB of PC patients in
      South Africa and Uganda is needed to improve spiritual care.

PMID- 22360992
TI  - Higher-order chromatin structure: bridging physics and biology.
AB  - Advances in microscopy and genomic techniques have provided new insight into
      spatial chromatin organization inside of the nucleus. In particular, chromosome
      conformation capture data has highlighted the relevance of polymer physics for
      high-order chromatin organization. In this context, we review basic polymer
      states, discuss how an appropriate polymer model can be determined from
      experimental data, and examine the success and limitations of various polymer
      models of higher-order interphase chromatin organization. By taking into account
      topological constraints acting on the chromatin fiber, recently developed polymer
      models of interphase chromatin can reproduce the observed scaling of distances
      between genomic loci, chromosomal territories, and probabilities of contacts
      between loci measured by chromosome conformation capture methods. Polymer models
      provide a framework for the interpretation of experimental data as ensembles of
      conformations rather than collections of loops, and will be crucial for
      untangling functional implications of chromosomal organization.

PMID- 22360994
TI  - Changes in the pore network structure of Hanford sediment after reaction with
      caustic tank wastes.
AB  - At the former nuclear weapon production site in Hanford, WA, caustic radioactive
      tank waste leaks into subsurface sediments and causes dissolution of quartz and
      aluminosilicate minerals, and precipitation of sodalite and cancrinite. This work
      examines changes in pore structure due to these reactions in a previously
      conducted column experiment. The column was sectioned and 2D images of the pore
      space were generated using backscattered electron microscopy and energy
      dispersive X-ray spectroscopy. A pre-precipitation scenario was created by
      digitally removing mineral matter identified as secondary precipitates. Porosity,
      determined by segmenting the images to distinguish pore space from mineral
      matter, was up to 0.11 less after reaction. Erosion-dilation analysis was used to
      compute pore and throat size distributions. Images with precipitation had more
      small and fewer large pores. Precipitation decreased throat sizes and the
      abundance of large throats. These findings agree with previous findings based on
      3D X-ray CMT imaging, observing decreased porosity, clogging of small throats,
      and little change in large throats. However, 2D imaging found an increase in
      small pores, mainly in intragranular regions or below the resolution of the 3D
      images. Also, an increase in large pores observed via 3D imaging was not observed
      in the 2D analysis. Changes in flow conducting throats that are the key
      permeability-controlling features were observed in both methods.

PMID- 22360993
TI  - The biology of personalized cancer medicine: facing individual complexities
      underlying hallmark capabilities.
AB  - It is a time of great promise and expectation for the applications of knowledge
      about mechanisms of cancer toward more effective and enduring therapies for human
      disease. Conceptualizations such as the hallmarks of cancer are providing an
      organizing principle with which to distill and rationalize the abject
      complexities of cancer phenotypes and genotypes across the spectrum of the human
      disease. A countervailing reality, however, involves the variable and often
      transitory responses to most mechanism-based targeted therapies, returning full
      circle to the complexity, arguing that the unique biology and genetics of a
      patient's tumor will in the future necessarily need to be incorporated into the
      decisions about optimal treatment strategies, the frontier of personalized cancer
      medicine. This perspective highlights considerations, metrics, and methods that
      may prove instrumental in charting the landscape of evaluating individual tumors
      so to better inform diagnosis, prognosis, and therapy. Integral to the
      consideration is remarkable heterogeneity and variability, evidently embedded in
      cancer cells, but likely also in the cell types composing the supportive and
      interactive stroma of the tumor microenvironment (e.g., leukocytes and
      fibroblasts), whose diversity in form, regulation, function, and abundance may
      prove to rival that of the cancer cells themselves. By comprehensively
      interrogating both parenchyma and stroma of patients' cancers with a suite of
      parametric tools, the promise of mechanism-based therapy may truly be realized.

PMID- 22360995
TI  - Inhibition of corneal inflammation following keratoplasty by birch leaf extract.
AB  - The objective of this study was to determine the effect of birch leaf (Betula
      pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat
      model. T cells were stimulated in vitro in the presence of BPE. Proliferation,
      activation phenotype and the number of apoptotic/necrotic cells in cell culture
      were analyzed by flow cytometry. Corneal transplantation was performed between
      Fisher and Lewis rats. Recipient rats were either treated with cyclosporine A at
      a low dosage (Low-dose CsA=LDCsA) or received LDCsA in combination with BPE
      (2*1ml/day). Clinical signs for corneal inflammation and rejection time points
      were determined. Infiltrating leukocytes were analyzed histologically. BPE
      specifically inhibited T cell proliferation in vitro by inducing apoptosis. The
      phenotype was not affected. In vivo, BPE significantly delayed the onset of
      corneal opacification (p<0.05). The amount of infiltrating CD45(+) leukocytes and
      CD4(+) T cells (p<0.001) was significantly reduced by BPE, whereas infiltration
      of CD163(+) macrophages was not significantly different between the two groups.
      BPE selectively induces apoptosis of activated T cells. Accordingly, BPE
      treatment significantly reduces infiltrating T cells and subsequent corneal
      opacification following keratoplasty. Our findings suggest BPE as a promising
      anti-inflammatory drug to treat corneal inflammation.

PMID- 22360997
TI  - Identification of mealybug pest species (Hemiptera: Pseudococcidae) in Egypt and
      France, using a DNA barcoding approach.
AB  - Pseudococcidae (mealybugs) is a large taxonomic group, including a number of
      agronomic pests. Taxonomic identification of mealybug species is a recurrent
      problem and represents a major barrier to the establishment of adequate pest
      management strategies. We combined molecular analysis of three DNA markers (28S
      D2, cytochrome oxidase I and internal transcribed spacer 2) with morphological
      examination, for the identification of 176 specimens collected from 40 mealybug
      populations infesting various crops and ornamental plants in Egypt and France.
      This combination of DNA and morphological analyses led to the identification of
      17 species: seven in Egypt (Planococcus citri (Risso), Planococcus ficus
      (Signoret), Maconellicoccus hirsutus (Green), Ferrisia virgata (Cockerell),
      Phenacoccus solenopsis Tinsley, Phenacoccus parvus Morrison and Saccharicoccus
      sacchari (Cockerell)) and 11 in France (Planococcus citri, Pseudococcus viburni
      Signoret, Pseudococcus longispinus (Targioni-Tozzetti), Pseudococcus comstocki
      (Kuwana), Rhizoecus amorphophalli Betrem, Trionymus bambusae (Green),
      Balanococcus diminutus (Leonardi), Phenacoccus madeirensis Green, Planococcus
      vovae (Nasonov), Dysmicoccus brevipes (Cockerell) and Phenacoccus aceris
      Signoret), Pl. citri being found in both countries. We also found genetic
      variation between populations considered to belong to the same species,
      justifying further investigation of the possible occurrence of complexes of
      cryptic taxa. 

PMID- 22360996
TI  - Determinants of left ventricular mass in patients on hemodialysis: Frequent
      Hemodialysis Network (FHN) Trials.
AB  - BACKGROUND: An increase in left ventricular mass (LVM) is associated with
      mortality and cardiovascular morbidity in patients with end-stage renal disease.
      METHODS AND RESULTS: The Frequent Hemodialysis Network (FHN) Daily Trial
      randomized 245 patients to 12 months of 6 times per week daily in-center
      hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87
      patients to 12 months of 6 times per week nocturnal hemodialysis or conventional
      hemodialysis. The main cardiac secondary outcome was change in LVM. In each
      trial, we examined whether several predefined baseline demographic or clinical
      factors as well as change in volume removal, blood pressure, or solute clearance
      influenced the effect of frequent hemodialysis on LVM. In the Daily Trial,
      frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI,
      5.0-21.3 g; P=0.002), LVM index (6.9 g/m(2); 95% CI, 2.4-11.3 g/m(2); P=0.003),
      and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%-12.6; P=0.02).
      Similar trends were noted in the Nocturnal Trial but did not reach statistical
      significance. In the Daily Trial, a more pronounced effect of frequent
      hemodialysis on LVM was evident among patients with left ventricular hypertrophy
      at baseline. Changes in LVM were associated with changes in blood pressure
      (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001)
      and were not significantly associated with changes in other parameters.
      CONCLUSIONS: Frequent in-center hemodialysis reduces LVM. The benefit of frequent
      hemodialysis on LVM may be mediated by salutary effects on blood pressure.
      Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00264758.

PMID- 22360998
TI  - The identification and oxidative stress response of a zeta class glutathione S
      transferase (GSTZ1) gene from Apis cerana cerana.
AB  - Glutathione-S-transferases (GSTs) play an important role in protecting organisms
      against the toxicity of reactive oxygen species (ROS). However, no information is
      available for GSTs in the Chinese honey bee (Apis cerana cerana). In this study,
      we isolated and characterized a zeta class GST gene (AccGSTZ1) from the Chinese
      honey bee. This gene is present in a single copy and harbors five exons. The
      deduced amino acid sequence of AccGSTZ1 shared high sequence identity with
      homologous proteins and contained the highly conserved features of this gene
      family. The temporal and spatial expression profiles of AccGSTZ1 showed that
      AccGSTZ1 was highly expressed in fourth instar larvae during development, and the
      mRNA level of AccGSTZ1 was higher in the epidermis than that in other tissues.
      The expression pattern under oxidative stress revealed that AccGSTZ1
      transcription was significantly upregulated by external factors, such as
      temperature challenges and H(2)O(2) treatment. The characterization of the
      purified protein revealed that AccGSTZ1 had low glutathione-conjugating activity,
      but the recombinant AccGSTZ1 protein displayed high antioxidant activity under
      oxidative stress. These data suggest that AccGSTZ1 is an oxidative stress
      inducible antioxidant enzyme that plays an important role in the protection
      against oxidative stress and may be of critical importance for the survival of
      the honey bees.

PMID- 22360999
TI  - Photoperiodic regulation of cold tolerance and expression levels of regucalcin
      gene in Drosophila montana.
AB  - Temperature-induced plasticity of cold tolerance has been reported in many insect
      species, but cold tolerance can also be affected by changes in day (or night)
      length. In the present study we elucidate the direct and indirect effects of
      photoperiod on the cold tolerance of females of two Drosophila montana strains-
      one which possesses a robust photoperiodic diapause and another which does not.
      In the diapause-strain the time needed for recovery from chill coma showed a
      positive correlation with day length, but diapause itself played only a minor
      role in photoperiodic acclimation. The strain that was not able to enter to
      diapause as a response to day length also lacked photoperiodic cold acclimation
      ability indicating that this strain has deficiencies in its photoperiodic time
      measurement system. In the diapause-strain, the expression level of regucalcin
      gene was more than two times higher in diapausing than in non-diapausing females
      maintained in a single photoperiod, but day length per se did not cause
      significant changes in expression levels of this gene in either of the strains.
      In the non-diapausing strain this gene showed no expression changes in any
      comparison. Overall, the study shows that a decrease in day length can induce
      cold acclimation in D. montana, while changes in regucalcin expression are linked
      with photoperiodic diapause.

PMID- 22361000
TI  - Disease severity declines over time after a wild boar population has been
      affected by classical swine fever--legend or actual epidemiological process?
AB  - Classical swine fever (CSF) is a severe multi-systemic disease that can affect
      both domestic pigs and wild boar. Past outbreaks in European wild boar involved
      high-virulent CSF virus (CSFV) strains and were mostly self-limiting. In these
      cases, morbidity and mortality rates were high in the affected regions. In
      contrast, endemic infections have been observed in several European wild boar
      populations in recent decades. Morbidity and mortality rates were much lower
      despite the fact that outbreaks were still detected via diseased or fallen
      animals. The virus strains involved were mostly classified as genotype 2.3
      strains of moderate virulence causing age-dependent disease outcomes. The
      mechanisms leading to the establishment and perpetuation of endemicity are still
      not fully understood, but the factor "moderate virulence" seems to be of
      considerable importance. In this study, we aim to clarify whether the perception
      of declined 'CSF severity' could hypothetically reflect the adaptation of an
      initially high-virulent virus or whether this might be better explained as a
      misinterpretation of observations. A mechanistic eco-epidemiological model was
      employed to follow up a highly virulent strain of CSFV introduced into large
      connected wild boar populations. In the model, the virulence of the CSF virus is
      represented by case mortality and life expectancy after lethal infection.
      Allowing for small stochastic variation, these two characteristics of the virus
      are passed on with every new simulated infection that occurs. Model analysis
      revealed a decrease from high to moderate case mortality within a few years of
      simulated perpetuation of the virus. The resulting mortality corresponded to the
      level where the population average of the infectious period and the basic
      reproduction number of the disease were maximal. This shift in virulence was
      sufficient to prolong virus circulation considerably beyond the epidemic phase of
      the simulated outbreaks. Alternative mechanistic explanations for the decrease in
      disease severity in a CSF-affected wild boar population were evaluated in the
      light of the simulation experiments and the available epidemiological or
      virological evidence. In conclusion, the current virus isolates of subgroup 2.3
      might be the ideally adapted variants of the CSF virus for long-term perpetuation
      in wildlife and indeed may have evolved (once) during past outbreaks in large
      populations. A repeated perception of a declining severity of disease pattern
      during the course of a CSF outbreak, however, favours the explanation based on
      monitoring and detection biases rather than repeated observation of selection
      against highly virulent virus during the time of virus perpetuation.

PMID- 22361001
TI  - Development of biodegradable scaffolds based on magnetically guided assembly of
      magnetic sugar particles.
AB  - Biodegradable scaffolds with controlled pore layout and porosity have great
      significance in tissue engineering for cell penetration, tissue ingrowth,
      vascularization, and nutrient delivery. Porogen leaching has been commonly used
      to control pore size, pore structure and porosity in the scaffold. In this paper
      we focus on the use/development of two magnetically guided porogen assembly
      methods using magnetic sugar particles (MSPs) for scaffold fabrication. First, a
      patterning device is utilized to align MSPs following designed templates. Then a
      magnetic sheet film is fabricated by mixing poly(vinyl alcohol, PVA) and NdFeB
      powder for steering the MSPs. After poly(l-lactide-co-E-caprolactone) (PLCL)
      casting and removal of the sugar template, a scaffold with spherical pores is
      obtained. The surface and the inner structure of the scaffolds are evaluated
      using light and electron micrographs showing their interconnection of pores, pore
      wall morphology and porosity. Single layer scaffolds with the size of 8mm in
      width and 10mm in length were constructed with controllable pore diameters in the
      ranges of 105-150 MUm, 250-300 MUm and 425-500 MUm.

PMID- 22361002
TI  - Inhibition by fatty acids during fermentation of pre-treated waste activated
      sludge.
AB  - Fermentation of waste activated sludge produces volatile fatty acids (VFAs),
      which can be used as the carbon sources for numerous biological processes.
      However, product inhibition can limit extent of fermentation to VFAs. In this
      study, product inhibition during fermentation of waste activated sludge pre
      treated by a thermal hydrolysis process (THP-WAS) was investigated. Product
      inhibition was confirmed as spiking reactors with high levels of a mix of VFAs
      prevented fermentation taking place. Various inhibition models were trialled and
      it was found that a threshold model (based on thermodynamics) provided the best
      fit between model and data. This is the first time that threshold type inhibition
      has been shown for a mixed substrate, mixed population system. Batch
      fermentations carried out with THP-WAS of different dilutions were used to
      evaluate the impact of different organic loadings. The threshold VFA
      concentration for the systems studied was determined to be 17+/-1gCOD(VFA)L(-1).
      Inhibition was shown to be due to the presence of a combination of VFAs
      containing 2-6 carbon atoms each. When evaluated individually, by spiking
      individual VFAs, all VFAs except for acetate had the same impact at this
      threshold; acetate being approximately 50% as inhibitory as the other organic
      acids (COD basis). Based on this, a weighted model could be proposed to better
      represent the data. Strategies to improve overall yield could be increased
      production of acetate, or dilution to below the inhibitory level.

PMID- 22361003
TI  - An evaluation of the feasibility, cost and value of information of a multicentre
      randomised controlled trial of intravenous immunoglobulin for sepsis (severe
      sepsis and septic shock): incorporating a systematic review, meta-analysis and
      value of information analysis.
AB  - BACKGROUND: Sepsis is a syndrome characterised by a systemic inflammatory
      response to infection that leads to rapid acute organ failure and potentially
      rapid decline to death. Intravenous immunoglobulin (IVIG), a blood product
      derived from human donor blood, has been proposed as an adjuvant therapy for
      sepsis. OBJECTIVES: To describe current practice in the management of adult
      patients severely ill with sepsis (severe sepsis or septic shock) in the UK; to
      assess the clinical effectiveness of IVIG for severe sepsis and septic shock and
      to obtain the appropriate inputs for the relative efficacy parameters, and the
      key uncertainties associated with these parameters, required to populate the
      decision model; to develop a decision-analytic model structure and identify key
      parameter inputs consistent with the decision problem and relevant to an NHS
      setting; and to populate the decision model and determine the cost-effectiveness
      of IVIG and to estimate the value of additional primary research. DATA SOURCES:
      Existing literature on IVIG and severe sepsis. Existing case-mix and outcome data
      on critical care admissions. Survey data on management of admissions with severe
      sepsis. Databases searched for clinical effectiveness were Cochrane Infectious
      Diseases Group Specialized Trials Register, the Cochrane Trials Register, MEDLINE
      and EMBASE. Dates searched were 1 January 2002 to 2 October 2009 to update
      previous Cochrane review. Databases searched for cost-effectiveness were NHS
      Economic Evaluation Database (NHS EED) to 2 October 2009, MEDLINE, MEDLINE In
      Process & Other Non-Indexed Citations and EMBASE to 20 October 2009. REVIEW
      METHODS: Systematic literature searching with data extraction, descriptive
      analysis and clinical effectiveness and cost-effectiveness modelling of IVIG in
      severe sepsis. Additional primary data analysis. Expected value of information
      (EVI) analysis. RESULTS: Our meta-analysis, the first to simultaneously allow for
      type of IVIG (IVIG or immunoglobulin M-enriched polyclonal IVIG), choice of
      control (no treatment or albumin), study quality/publication bias and other
      potential covariates, indicated that the treatment effect of IVIG on mortality
      for patients with severe sepsis is borderline significant with a large degree of
      heterogeneity in treatment effect between individual studies. Modelling indicated
      that there were issues with bias associated with trial methodology, publication
      and small-study effects with the current evidence. The large degree of
      heterogeneity in treatment effects between studies, however, could be explained
      (best-fitting model) by a measure of study quality (i.e. use of albumin as
      control - as an indicator of proper blinding to treatment as a proxy for study
      quality - associated with decreased effect) and duration of IVIG therapy (longer
      duration associated with increased effect). In-depth discussion within the Expert
      Group on duration of IVIG therapy, with daily dose and total dose also clearly
      inter-related, indicated no clear clinical rationale for this association and
      exposed a lack of evidence on the understanding of the mechanism of action of
      IVIG in severe sepsis. Although the EVI analyses suggested substantial expected
      net benefit from a large, multicentre randomised controlled trial (RCT)
      evaluating the clinical effectiveness of IVIG, the remaining uncertainties around
      the design of such a study mean that we are unable to recommend it at this time.
      LIMITATIONS: As has been identified in previous meta-analyses, there are issues
      with the methodological quality of the available evidence. CONCLUSIONS: Although
      the results highlight the value for money obtained in conducting further primary
      research in this area, the biggest limitation for such research regards the
      uncertainties over the mechanism of action of IVIG and the heterogeneous nature
      of severe sepsis. Resolving these would allow for better definition of the
      plausibility of the effectiveness scenarios presented and, consequently, a better
      understanding of the cost-effectiveness of this treatment. This information would
      also inform the design of future, primary evaluative research. Our
      recommendations for future research focus on filling the knowledge gaps to inform
      a future multicentre RCT prior to recommending its immediate design and conduct.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 22361004
TI  - Biologic failure of a ligament advanced reinforcement system artificial ligament
      in anterior cruciate ligament reconstruction: a report of serious knee synovitis.
AB  - A ligament advanced reinforcement system (LARS) artificial ligament has been
      proposed for use in anterior cruciate ligament reconstruction in some cases, and
      an emerging body of reports has shown its success in the short term. However,
      there are great concerns about the potential risks of complications, which might
      prevent its extensive use. We report a rare case of serious synovitis 3 years
      postoperatively in a 26-year-old man who underwent LARS artificial ligament
      reconstruction. During revision arthroscopy, we observed a large amount of
      synovial hyperplasia in the knee joint, containing a large amount of hemosiderin
      deposition. In addition, the femoral tunnel was placed too anteriorly, and the
      ligament was ruptured near the tibial tunnel. Histologically, there was thick
      fibrous scar tissue around the graft, and poorly organized fibrous scar tissue
      infiltrated into the graft fibers, which could cause loss of structural integrity
      of the ligament and eventual graft failure. Collectively, our findings might
      arouse further in-depth research on the development of artificial ligament.

PMID- 22361005
TI  - Long term antibiotic therapy may be an effective treatment for children co-morbid
      with Lyme disease and autism spectrum disorder.
AB  - Patients diagnosed with Lyme disease share many of the same physical
      manifestations as those diagnosed with an Autism Spectrum Disorder (ASD). In this
      study four male children (ages 26-55 months) who have an ASD diagnosis and one
      male child (age -O meets state and federal requirements for providing a
      comprehensive, ongoing assessment of a child with an ASD [33]. The SAP-O form
      measures children's abilities using observational, authentic assessment
      procedures in the domains of joint attention, symbol use, mutual regulation, and
      self regulation via observations of specific behaviors in familiar settings [33].
      The five children tested positive for Lyme disease and their SAP-O score was
      evaluated before and after 6 months of antibiotic therapy. Each child was
      prescribed 200mg of amoxicillin three times per day and three of the five
      children were prescribed an additional 50mg of Azithromycin once per day. All of
      the children's scores on the SAP-O assessment improved after 6 months of
      antibiotic therapy. The assessors also reported anecdotal data of improved
      speech, eye contact, sleep behaviors, and a reduction of repetitive behaviors.

PMID- 22361006
TI  - The National CT Colonography Trial: assessment of accuracy in participants 65
      years of age and older.
AB  - PURPOSE: To conduct post-hoc analysis of National CT Colonography Trial data and
      compare the sensitivity and specificity of computed tomographic (CT) colonography
      in participants younger than 65 years with those in participants aged 65 years
      and older. MATERIALS AND METHODS: Of 2600 asymptomatic participants recruited at
      15 centers for the trial, 497 were 65 years of age or older. Approval of this
      HIPAA-compliant study was obtained from the institutional review board of each
      site, and informed consent was obtained from each subject. Radiologists certified
      in CT colonography reported lesions 5 mm in diameter or larger. Screening
      detection of large (>=10-mm) histologically confirmed colorectal neoplasia was
      the primary end point; screening detection of smaller (6-9-mm) colorectal
      neoplasia was a secondary end point. The differences in sensitivity and
      specificity of CT colonography in the two age cohorts (age < 65 years and age >=
      65 years) were estimated with bootstrap confidence intervals (CIs). RESULTS:
      Complete data were available for 477 participants 65 years of age or older (among
      2531 evaluable participants). Prevalence of adenomas 1 cm or larger for the older
      participants versus the younger participants was 6.9% (33 of 477) versus 3.7% (76
      of 2054) (P < .004). For large neoplasms, mean estimates for CT colonography
      sensitivity and specificity among the older cohort were 0.82 (95% CI: 0.644,
      0.944) and 0.83 (95% CI: 0.779, 0.883), respectively. For large neoplasms in the
      younger group, CT colonography sensitivity and specificity were 0.92 (95% CI:
      0.837, 0.967) and 0.86 (95% CI: 0.816, 0.899), respectively. Per-polyp
      sensitivity for large neoplasms for the older and younger populations was 0.75
      (95% CI: 0.578, 0.869) and 0.84 (95% CI: 0.717, 0.924), respectively. For the
      older and younger groups, per-participant sensitivity was 0.72 (95% CI: 0.565,
      0.854) and 0.81 (95% CI: 0.745, 0.882) for detecting adenomas 6 mm in diameter or
      larger. CONCLUSION: For most measures of diagnostic performance and in most
      subsets, the difference between senior-aged participants and those younger than
      65 years was not statistically significant.

PMID- 22361007
TI  - An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides
      in human macrophages.
AB  - Cytosolic pathogen- and damage-associated molecular patterns are sensed by
      pattern recognition receptors, including members of the nucleotide-binding domain
      and leucine-rich repeat-containing gene family (NLR), which cause inflammasome
      assembly and caspase-1 activation to promote maturation and release of the
      inflammatory cytokines interleukin-1beta (IL-1beta) and IL-18 and induction of
      pyroptosis. However, the contribution of most of the NLRs to innate immunity,
      host defense, and inflammasome activation and their specific agonists are still
      unknown. Here we describe identification and characterization of an NLRP7
      inflammasome in human macrophages, which is induced in response to microbial
      acylated lipopeptides. Activation of NLRP7 promoted ASC-dependent caspase-1
      activation, IL-1beta and IL-18 maturation, and restriction of intracellular
      bacterial replication, but not caspase-1-independent secretion of the
      proinflammatory cytokines IL-6 and tumor necrosis factor-alpha. Our study
      therefore increases our currently limited understanding of NLR activation,
      inflammasome assembly, and maturation of IL-1beta and IL-18 in human macrophages.

PMID- 22361008
TI  - A proactive smoking cessation intervention in postpartum women.
AB  - OBJECTIVE: to analyse the efficacy of a proactive intervention during the
      postpartum period to prevent a relapse in recent quitters and to promote progress
      in the behavioural process of change in smokers. DESIGN: randomised controlled
      trial designed for women at the end of the pregnancy using a proactive
      intervention. Motivational Interviewing (MI) and relapse prevention served as
      principles for the programme. In the intervention group, four telephone
      supporting sessions were performed in weeks 3, 6, 9 and 12. For the control group
      only two check calls in weeks 3 and 12. SETTING: women who attended the
      University Clinical Hospital 'Lozano Blesa' of Zaragoza (Spain) to give birth
      between January 2009 and March 2010. The intervention began after delivery,
      lasted for 3 months, and finished with a visit to validate abstinence
      biochemically. FINDINGS: a total of 2,044 women were studied, 30.6% (n=626)
      smoked before pregnancy; 65.8% (n=412) of them agreed to participate. The results
      for recent quitters by self-report showed that the probability of remaining
      abstinent after 12 weeks was 74% for the intervention group and 37% for the
      control group. Only the half of the sample attended the visit at 3 months to
      confirm the abstinence biochemically. For smokers, 90.7% of the intervention
      group said that they would be ready to try to quit in the following 6 months, vs.
      18.3% for the control group. CONCLUSIONS AND IMPLICATIONS FOR THE PRACTICE: a
      proactive intervention in the postpartum period may reduce the probability of
      relapse in recent quitters and helps female smokers to make progress in the
      behavioural process of change. Such interventions should be included
      systematically in mother-child health services.

PMID- 22361009
TI  - Maternal depression and physical health problems in early pregnancy: findings of
      an Australian nulliparous pregnancy cohort study.
AB  - OBJECTIVE: to investigate the relationship between physical health problems and
      depressive symptoms in early pregnancy. DESIGN: baseline questionnaire,
      prospective pregnancy cohort study. SETTING: six metropolitan public maternity
      hospitals in Victoria, Australia. PARTICIPANTS: 1507 nulliparous women recruited
      in early pregnancy. FINDINGS: nine per cent of women (131/1500) scored >= 13 on
      the EPDS indicating probable clinical depression in early pregnancy (mean
      gestation=15 weeks). The five most commonly reported physical health problems
      were as follows: exhaustion (86.9%), morning sickness (64.3%), back pain (45.6%),
      constipation (43.5%) and severe headaches or migraines (29.5%). Women scoring >=
      13 on the EPDS reported a mean of six physical health problems compared with a
      mean of 3.5 among women scoring <13 on the EPDS. Women reporting five or more
      physical health problems had a three-fold increase in likelihood of reporting
      depressive symptoms (Adj OR=3.13, 95% CI 2.14-4.58) after adjusting for socio
      demographic factors, including maternal age. CONCLUSIONS: the findings from this
      large multi-centre study show that women experiencing a greater number of
      physical health problems are at increased risk of reporting depressive symptoms
      in early pregnancy. IMPLICATIONS FOR PRACTICE: early detection and support for
      women experiencing physical and psychological health problems in pregnancy is an
      important aspect of antenatal care. The extent of co-morbid physical and
      psychological health problems underlines the need for comprehensive primary
      health care as an integral component of antenatal care.

PMID- 22361012
TI  - Graphical representation of QT rate correction formulae: an aid facilitating the
      use of a given formula and providing a visual comparison of the impact of
      different formulae.
AB  - The QT interval on the electrocardiogram is an increasingly important
      measurement, especially in relation to drug action and interaction. The QT
      interval varies inversely as the heart rate and numerous rate correction formulae
      have been proposed. It is difficult to compare the effect of applying different
      formulae at different heart rates and for different measured QT intervals. A
      simple graphical display of the results from different formulae is proposed. This
      display is dependent on the concept of the absolute correction factor. This
      graphical presentation is useful (a) in comparing the effect of the application
      of different formulae and (b) in directly reading the correction produced by any
      individual formula.

PMID- 22361013
TI  - Corneal changes following short-term rigid contact lens wear.
AB  - PURPOSE: The aim of this cross-over study was to investigate the changes in
      corneal thickness, anterior and posterior corneal topography, corneal refractive
      power and ocular wavefront aberrations, following the short term use of rigid
      contact lenses. METHOD: Fourteen participants wore 4 different types of contact
      lenses (RGP lenses of 9.5mm and 10.5mm diameter, and for comparison a PMMA lens
      of 9.5mm diameter and a soft silicone hydrogel lens) on 4 different days for a
      period of 8h on each day. Measures were collected before and after contact lens
      wear and additionally on a baseline day. RESULTS: Anterior corneal curvature
      generally showed a flattening with both of the RGP lenses and a steepening with
      the PMMA lens. A significant negative correlation was found between the change in
      corneal swelling and central and peripheral posterior corneal curvature (all p <=
      0.001). RGP contact lenses caused a significant decrease in corneal refractive
      power (hyperopic shift) of approximately 0.5D. The PMMA contact lenses caused the
      greatest corneal swelling in both the central (27.92 +/- 15.49 MUm, p<0.001) and
      peripheral (17.78 +/- 12.11 MUm, p=0.001) corneal regions, a significant
      flattening of the posterior cornea and an increase in ocular aberrations (all p
      <= 0.05). CONCLUSION: The corneal swelling associated with RGP lenses was
      relatively minor, but there was slight central corneal flattening and a
      clinically significant hyperopic change in corneal refractive power after the
      first day of lens wear. The PMMA contact lenses resulted in significant corneal
      swelling and reduced optical performance of the cornea.

PMID- 22361010
TI  - Is inhibition of kinase activity the only therapeutic strategy for LRRK2
      associated Parkinson's disease?
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of
      familial Parkinson's disease (PD). Variation around the LRRK2 locus also
      contributes to the risk of sporadic PD. The LRRK2 protein contains a central
      catalytic region, and pathogenic mutations cluster in the Ras of complex protein
      C terminus of Ras of complex protein (mutations N1437H, R1441G/C and Y1699C) and
      kinase (G2019S and I2020T) domains. Much attention has been focused on the kinase
      domain, because kinase-dead versions of mutant LRRK2 are less toxic than kinase
      active versions of the same proteins. Furthermore, kinase inhibitors may be able
      to mimic this effect in mouse models, although the currently tested inhibitors
      are not completely specific. In this review, we discuss the recent progress in
      the development of specific LRRK2 kinase inhibitors. We also discuss non-kinase
      based therapeutic strategies for LRRK2-associated PD as it is possible that
      different approaches may be needed for different mutations.

PMID- 22361011
TI  - Bioinformatic identification of cassava miRNAs differentially expressed in
      response to infection by Xanthomonas axonopodis pv. manihotis.
AB  - BACKGROUND: microRNAs (miRNAs) are short RNA molecules that control gene
      expression by silencing complementary mRNA. They play a crucial role in stress
      response in plants, including biotic stress. Some miRNAs are known to respond to
      bacterial infection in Arabidopsis thaliana but it is currently unknown whether
      these responses are conserved in other plants and whether novel species-specific
      miRNAs could have a role in defense. RESULTS: This work addresses the role of
      miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis
      (Xam) interaction. Next-generation sequencing was used for analyzing small RNA
      libraries from cassava tissue infected and non-infected with Xam. A full
      repertoire of cassava miRNAs was characterized, which included 56 conserved
      families and 12 novel cassava-specific families. Endogenous targets were
      predicted in the cassava genome for many miRNA families. Some miRNA families'
      expression was increased in response to bacterial infection, including miRNAs
      known to mediate defense by targeting auxin-responding factors as well as some
      cassava-specific miRNAs. Some bacteria-repressed miRNAs included families
      involved in copper regulation as well as families targeting disease resistance
      genes. Putative transcription factor binding sites (TFBS) were identified in the
      MIRNA genes promoter region and compared to promoter regions in miRNA target
      genes and protein coding genes, revealing differences between MIRNA gene
      transcriptional regulation and other genes. CONCLUSIONS: Taken together these
      results suggest that miRNAs in cassava play a role in defense against Xam, and
      that the mechanism is similar to what's known in Arabidopsis and involves some of
      the same families.

PMID- 22361016
TI  - Radioactive cesium isotope ratios as a tool for determining dispersal and re
      dispersal mechanisms downwind from the Nevada Nuclear Security Site.
AB  - Fractionation of the two longer-lived radioactive cesium isotopes ((135)Cs and
      (137)Cs) produced by above ground nuclear tests have been measured and used to
      clarify the dispersal mechanisms of cesium deposited in the area between the
      Nevada Nuclear Security Site and Lake Mead in the southwestern United States.
      Fractionation of these isotopes is due to the 135-decay chain requiring several
      days to completely decay to (135)Cs, and the 137-decay chain less than one hour
      decay to (137)Cs. Since the Cs precursors are gases, iodine and xenon, the
      (135)Cs plume was deposited farther downwind than the (137)Cs plume. Sediment
      core samples were obtained from the Las Vegas arm of Lake Mead, sub-sampled and
      analyzed for (135)Cs/(137)Cs ratios by thermal ionization mass spectrometry. The
      layers proved to have nearly identical highly fractionated isotope ratios. This
      information is consistent with a model where the cesium was initially deposited
      onto the land area draining into Lake Mead and the composite from all of the
      above ground shots subsequently washed onto Lake Mead by high intensity rain and
      wind storms producing a layering of Cs activity, where each layer is a portion of
      the composite.

PMID- 22361014
TI  - Carcinoma of endocrine organs: results of the RARECARE project.
AB  - The rarity or the asymptomatic character of endocrine tumours results in a lack
      of epidemiological studies on their incidence and survival patterns. The aim of
      this study was to describe the incidence, prevalence and survival of endocrine
      tumours using a large database, which includes cancer patients diagnosed from
      1978 to 2002, registered in 89 population-based cancer registries (CRs) with
      follow-up until 31st December 2003. These data give an unique overview of the
      burden of endocrine carcinomas in Europe. A list of tumour entities based on the
      third International Classification of Diseases for Oncology was provided by the
      project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594
      cases of endocrine carcinomas were analysed in this study. Incidence rates
      increased with age and were highest in patients 65 years of age or older. In
      2003, more than 315,000 persons in the EU (27 countries) were alive with a past
      diagnosis of a carcinoma of endocrine organs. The incidence of pituitary
      carcinoma equalled four per 1,000,000 person years and showed the strongest
      decline in survival with increasing age. Thyroid cancer showed the highest crude
      incidence rates (four per 100,000 person years) and was the only entity with a
      gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the
      rarest endocrine entity with two new cases per 10,000,000 person years. For
      adrenal carcinoma, the most remarkable observations were a higher survival for
      women compared to men (40% compared to 32%, respectively) and a particularly low
      relative survival of 24% in patients 65 years of age or older. More high quality
      studies on rare cancers, with additional information, e.g. on stage and
      therapeutic approach, are needed and may be of help in partly explaining the
      observed variation in survival.

PMID- 22361017
TI  - Prediction of the (137)Cs activity concentration in the atmospheric surface layer
      of the Chernobyl exclusion zone.
AB  - The time series of the 10-day average (137)Cs volumetric activity concentration
      in the lower atmosphere measured from 1987 to 1991 in the town of Pripyat, close
      to the Chernobyl nuclear power plant, was used to construct a model to predict
      the airborne activity concentration inside the 30-km exclusion zone. For that
      purpose, individual components of the observed time series were separated by
      regression analysis and the Group Method of Data Handling. The measured data in
      Pripyat were divided in two periods. The long-term prediction by the model
      established using the measured data of the first period, has been validated with
      the data in the second period with good agreement. The behaviour of the model
      parameters depending on the length of the periods was also analysed, and the
      first period of 4.5 y was shown as sufficient for estimating the parameters.
      Further increase in the length will not significantly enhance the model
      parameters and the predictive power.

PMID- 22361018
TI  - Trajectories of trauma symptoms and resilience in deployed U.S. military service
      members: prospective cohort study.
AB  - BACKGROUND: Most previous attempts to determine the psychological cost of
      military deployment have been limited by reliance on convenience samples, lack of
      pre-deployment data or confidentiality and cross-sectional designs. AIMS: This
      study addressed these limitations using a population-based, prospective cohort of
      U.S. military personnel deployed in support of the operations in Iraq and
      Afghanistan. METHOD: The sample consisted of U.S. military service members in all
      branches including active duty, reserve and national guard who deployed once (n =
      3393) or multiple times (n = 4394). Self-reported symptoms of post-traumatic
      stress were obtained prior to deployment and at two follow-ups spaced 3 years
      apart. Data were examined for longitudinal trajectories using latent growth
      mixture modelling. RESULTS: Each analysis revealed remarkably similar post
      traumatic stress trajectories across time. The most common pattern was low-stable
      post-traumatic stress or resilience (83.1% single deployers, 84.9% multiple
      deployers), moderate-improving (8.0%, 8.5%), then worsening-chronic post
      traumatic stress (6.7%, 4.5%), high-stable (2.2% single deployers only) and high
      improving (2.2% multiple deployers only). Covariates associated with each
      trajectory were identified. CONCLUSIONS: The final models exhibited similar types
      of trajectories for single and multiple deployers; most notably, the stable
      trajectory of low post-traumatic stress preto post-deployment, or resilience, was
      exceptionally high. Several factors predicting trajectories were identified,
      which we hope will assist in future research aimed at decreasing the risk of post
      traumatic stress disorder among deployers.

PMID- 22361019
TI  - Migration and autism spectrum disorder: population-based study.
AB  - BACKGROUND: Migration has been implicated as a risk factor for autism, but
      evidence is limited and inconsistent. AIMS: To investigate the relationship
      between parental migration status and risk of autism spectrum disorder, taking
      into consideration the importance of region of origin, timing of migration and
      possible discrepancies in associations between autism subtypes. METHOD: Record
      linkage study within the total child population of Stockholm County between 2001
      and 2007. Individuals with high- and low-functioning autism were defined as
      having autism spectrum disorder with and without comorbid intellectual
      disability, and ascertained via health and habilitation service registers.
      RESULTS: In total, 4952 individuals with autism spectrum disorder were
      identified, comprising 2855 children with high-functioning autism and 2097
      children with low-functioning autism. Children of migrant parents were at
      increased risk of low-functioning autism (odds ratio (OR) = 1.5, 95% CI 1.3-1.7);
      this risk was highest when parents migrated from regions with a low human
      development index, and peaked when migration occurred around pregnancy (OR = 2.3,
      95% CI 1.7-3.0). A decreased risk of high-functioning autism was observed in
      children of migrant parents, regardless of area of origin or timing of migration.
      Parental age, income or obstetric complications did not fully explain any of
      these associations. CONCLUSIONS: Environmental factors associated with migration
      may contribute to the development of autism presenting with comorbid intellectual
      disability, especially when acting in utero. High- and low-functioning autism may
      have partly different aetiologies, and should be studied separately.

PMID- 22361020
TI  - Functional magnetic resonance imaging correlates of memory encoding in relation
      to achieving remission in first-episode schizophrenia.
AB  - BACKGROUND: Previous studies in schizophrenia have shown a strong relationship
      between memory deficits and a poor clinical outcome. However, no previous study
      has identified the functional neural correlates of memory encoding in relation to
      remission. AIMS: To determine whether functional magnetic resonance imaging
      (fMRI) activation patterns differed between individuals that later achieved
      remission v. those who did not. METHOD: Forty-two participants with first-episode
      schizophrenia were divided into two groups after 1 year of treatment as per the
      2005 remission in schizophrenia consensus definition. We then examined fMRI
      activation using three contrasts (associative v. item-oriented strategy,
      semantically unrelated v. related image pairs, and successful v. unsuccessful
      memory encoding) among 15 participants who had achieved remission (remitted
      group), 27 who had not (non-remitted group) and 31 healthy controls (control
      group). RESULTS: Participants in the non-remitted group displayed a positive
      activation in the posterior cingulate compared with those in the remitted group
      when encoding related images; no significant differences between the two groups
      were identified for the other contrasts. From the behavioural data, compared with
      the remitted and control groups, the non-remitted group demonstrated an inability
      to encode related images and displayed worse recognition memory overall.
      CONCLUSIONS: This is the first study to identify differential neural activation
      between individuals with first-episode schizophrenia that later achieved
      remission v. those who did not. The behavioural and functional results together
      add to the growing evidence relating a poor clinical outcome in schizophrenia to
      memory-related deficits.

PMID- 22361021
TI  - Costs and outcomes of an intervention programme for offenders with personality
      disorders.
AB  - BACKGROUND: The dangerous severe personality disorder programme was developed in
      high secure prisons and hospitals at great expense to identify and treat the most
      dangerous offenders with personality disorders. AIMS: To evaluate whether the
      long-term costs of the programme are greater or less than the long-term outcomes.
      METHOD: We used a Markov decision model with a cost-effectiveness analysis to
      determine the incremental cost of the programme per serious offence prevented and
      a cost-offset analysis to consider whether monetary benefits were greater than
      costs. RESULTS: Costs were consistently higher for the intervention programme and
      the cost per serious offence prevented was over L2 million, although there was
      some evidence that adjustments to the programme could lead to similar
      interventions becoming cost-effective. CONCLUSIONS: Little evidence was found to
      support the cost-effectiveness of the intervention programme for offenders with
      personality disorders, although delivery of the programme in a lower-cost prison
      would probably yield greater benefits than costs. There are frequent calls for
      mentally disordered offenders to be detained in secure hospitals rather than
      prisons; however, if reoffending remains the outcome of interest for policy
      makers, it is likely that the costs of detention in hospital will remain greater
      than the benefits for dangerous offenders with a personality disorder.

PMID- 22361022
TI  - [Prevalence of obesity and cardiovascular risk in the general population of a
      health area in Extremadura (Spain): the Hermex study].
AB  - INTRODUCTION AND OBJECTIVES: To estimate the prevalence of obesity and its
      associated cardiovascular risk in the general population of a health area in
      Extremadura. MATERIALS AND METHODS: A cross-sectional study on a random
      population sample aged 25-79 years from the Don Benito-Villanueva (Badajoz)
      health area. Risk factors and cardiovascular disease were examined.
      Anthropometric and blood pressure measurements were collected, and a blood sample
      was taken. Obese subjects were categorized into different risk levels as proposed
      by the Spanish Society for the Study of Obesity, and the influence of obesity on
      estimation of the risk of ischemic heart disease was studied using the Framingham
      function, as adapted for Spain. RESULTS: A total of 2833 of the 3521 subjects
      screened (80.5%) participated in the study. Mean age was 51.2 years (SD 14.7),
      and 46.5% were males. Male subjects had a greater prevalence of overweight and
      obesity (46.2% and 37.7% respectively) as compared to females (37.7% and 32.6%)
      (p<0.005 and p<0.05 respectively). Only 10% of obese subjects had no increased
      cardiovascular risk. Obesity was associated to an 8-fold increase in the presence
      of a high risk for ischemic heart disease in females (p<0.001), as compared to a
      1.4-fold increase in males (p=0.095). CONCLUSIONS: Obesity is highly prevalent
      and affects, together with overweight, 74.1% of the population in an Extremadura
      health area. A vast majority of obese subjects have an increased cardiovascular
      risk, which is very marked for ischemic heart disease in females.

PMID- 22361023
TI  - Decreased expression of the glial water channel aquaporin-4 in the
      intrahippocampal kainic acid model of epileptogenesis.
AB  - Recent evidence suggests that astrocytes may be a potential new target for the
      treatment of epilepsy. The glial water channel aquaporin-4 (AQP4) is expressed in
      astrocytes, and along with the inwardly-rectifying K(+) channel K(ir)4.1 is
      thought to underlie the reuptake of H(2)O and K(+) into glial cells during neural
      activity. Previous studies have demonstrated increased seizure duration and
      slowed potassium kinetics in AQP4(-/-) mice, and redistribution of AQP4 in
      hippocampal specimens from patients with chronic epilepsy. However, the
      regulation and role of AQP4 during epileptogenesis remain to be defined. In this
      study, we examined the expression of AQP4 and other glial molecules (GFAP,
      K(ir)4.1, glutamine synthetase) in the intrahippocampal kainic acid (KA) model of
      epilepsy and compared behavioral and histologic outcomes in wild-type mice vs.
      AQP4(-/-) mice. Marked and prolonged reduction in AQP4 immunoreactivity on both
      astrocytic fine processes and endfeet was observed following KA status
      epilepticus in multiple hippocampal layers. In addition, AQP4(-/-) mice had more
      spontaneous recurrent seizures than wild-type mice during the first week after KA
      SE as assessed by chronic video-EEG monitoring and blinded EEG analysis. While
      both genotypes exhibited similar reactive astrocytic changes, granule cell
      dispersion and CA1 pyramidal neuron loss, there were an increased number of
      fluorojade-positive cells early after KA SE in AQP4(-/-) mice. These results
      indicate a marked reduction of AQP4 following KA SE and suggest that
      dysregulation of water and potassium homeostasis occurs during early
      epileptogenesis. Restoration of astrocytic water and ion homeostasis may
      represent a novel therapeutic strategy.

PMID- 22361025
TI  - Inactivation of Salmonella on whole cantaloupe by application of an antimicrobial
      coating containing chitosan and allyl isothiocyanate.
AB  - This study investigated the antimicrobial effect of a chitosan coating+allyl
      isothiocyanate (AIT) and nisin against Salmonella on whole fresh cantaloupes.
      Cantaloupes were inoculated with a cocktail of three Salmonella strains and
      treated with chitosan, chitosan+AIT, chitosan+nisin, and chitosan+AIT+nisin
      coatings. With AIT concentrations increasing from 10 to 60 MUl/ml, the
      antibacterial effects of coating treatments against Salmonella increased.
      Chitosan coatings with 60 MUl/ml AIT (chitosan+60AIT) reduced more than 5 log10
      CFU/cm2 of Salmonella. The addition of nisin to the chitosan-AIT coating
      synergistically increased the antibacterial effect; coatings with nisin (25 mg/ml
      or 25,000 IU/ml)+30 MUl/ml AIT resulted in a 4.8 log10 reduction of Salmonella.
      The chitosan+60AIT coating significantly (p<0.05) reduced populations of native
      bacteria on cantaloupes to ca. 2 log10 CFU/cm2 during the first 6 days and
      populations remained unchanged through day 14 at 10  degrees C. The same coating
      treatment completely inactivated mold and yeast on cantaloupe at day 1 and no
      regrowth occurred even up to 14 days of storage. Scanning electron microscopy
      revealed that cell membrane damage and leakage of intercellular components
      occurred as a result of the chitosan-AIT coating treatments. No visual changes in
      overall appearance and color of cantaloupe rind and flesh due to coating
      treatments were observed. These results indicate that the application of an
      antimicrobial coating may be an effective method for decontamination of
      cantaloupes.

PMID- 22361024
TI  - The lateral thoracic nerve and the cutaneous maximus muscle--a novel in vivo
      model system for nerve degeneration and regeneration studies.
AB  - We report a novel in vivo mouse model system to study regeneration of injured
      motor nerve and spatiotemporal pattern of denervation in experimental nerve
      diseases. The lateral thoracic nerve (LTN), as a pure motor nerve, innervates the
      cutaneous maximus muscle (CMM) by some of the shortest and the longest motor
      nerve fibers in the mouse body. Its branches and nerve terminals can be imaged in
      whole mount preparations. Here we describe the branching pattern of the LTN and
      its innervation of the CMM, and characterize degeneration and regeneration over
      time after a LTN crush by morphological and electrophysiological analyses. We
      demonstrate the utility of this model in a well-established neurotoxicity
      paradigm and in a genetic disease model of the peripheral neuropathy.
      Furthermore, this system enables punch biopsies that allow repeated and multi
      location examinations for LTN regeneration and CMM reinnervation over time. The
      presence of the LTN and the CMM in a variety of species and its easy
      accessibility suggests that this in vivo model system offers considerable promise
      for future nerve degeneration and regeneration research.

PMID- 22361026
TI  - [Corticosteroids and diabetes mellitus].
AB  - During corticosteroid prescriptions, diabetes mellitus may be completely
      deregulated or may be revealed as such. Predisposition to diabetes mellitus could
      be because of latent beta Langerhans cell deregulation or because enhancement of
      tissue sensitivity by glucocorticosteroids. However, epidemiologic data
      concerning predisposing factors and frequency of cortico-induced diabetes are not
      well known. Detection, treatment and prevention are the same as for type II
      diabetes. Glycemia should be monitored throughout long-term treatments.

PMID- 22361027
TI  - [Cardiovascular risks of corticosteroids].
AB  - Prolonged use of glucocorticoids is associated with an increase in cardiovascular
      morbidity and mortality: hypertension and atheroma mainly. Severe cardiovascular
      complications of pulse corticosteroids are related to underlying comobidities and
      require some precautions. There are probably individual factors of complications
      associated with polymorphisms of the glucocorticoid receptor. Without clearly
      established recommendations concerning prevention of cardiovascular risk,
      screening and treatment of risk factors during treatment is the best prevention
      possible. Screening and treatment of cardiovascular complications require a just
      prescription and appropriate surveillance.

PMID- 22361028
TI  - [A case of giant cell arteritis [correction of arthritis] diagnosed with 18FDG
      positron emission tomography].

PMID- 22361029
TI  - [Anti-inflammatory and immunosuppressive properties of corticosteroids].
AB  - Glucocorticoids exhibit anti-inflammatory, anti-allergic and immunosuppressive
      properties, which contribute to their beneficial therapeutic effects. The
      biological effects of their interaction with their soluble receptor have been
      investigated as well as their inhibitory effects on several proteins implicated
      in the inflammatory process and on the tissular steps of inflammation. In
      addition, glucocorticoids exert multiple inhibitory effects both on
      immunocompetent cells (mainly T-lymphocytes) and on cytokines. Their role on Th17
      lymphocytes and regulatory T cells has been recently studied and could represent
      new mechanisms of action of these drugs.

PMID- 22361031
TI  - Encapsulation of P-glycoprotein inhibitors by polymeric micelles can reduce their
      pharmacokinetic interactions with doxorubicin.
AB  - Co-administration of P-glycoprotein (P-gp) inhibitors such as cyclosporine A
      (CyA) and its analogue valspodar with doxorubicin (DOX) can result in diminished
      clearance of DOX, leading to accentuated toxicity. The purpose of this study was
      to evaluate whether the effect of these P-gp inhibitors on the pharmacokinetics
      of DOX can be avoided through their encapsulation in polymeric micelles.
      Cyclosporine A or valspodar was physically encapsulated in methoxypoly(ethylene
      oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) micelles using co-solvent
      evaporation method. The commercially available DOX was administered as a single
      dose of 5mg/kg intravenously to Sprague-Dawley rats either alone or 30min
      following a single intravenous dose (10mg/kg) of either CyA or valspodar as part
      of conventional or polymeric micellar formulation. Co-administration of DOX with
      either Sandimmune(r) or valspodar in the conventional Cremophor EL-based
      formulation was associated with greater than 50% reduction in DOX clearance (CL).
      Although there was nearly 40% reduction in the CL of DOX with the polymeric
      micellar formulation of CyA, there was only 6% reduction in CL of DOX upon co
      administration with the polymeric micellar formulation of valspodar. In
      conclusion, encapsulation of cyclosporines, particularly valspodar, in polymeric
      micelles was shown to reduce their effects on the pharmacokinetics of DOX in rat.

PMID- 22361032
TI  - Molecular detection of Torque teno sus virus from tissues samples of sick pigs in
      China.
AB  - In the present study, Torque teno sus virus (TTSuV) was detected from different
      tissues, stool and serum samples of 25 sick pigs. The total prevalence of TTSuV1
      and TTSuV2 were 64% (16/25) and 28% (7/25), 24% (6/25) were co-infected with both
      TTSuV1 and TTSuV2. The prevalence of TTSuV infection in spleen is a slightly
      higher, with positive rates of 52% (13/25) for TTSuV1 and 24% (6/25) for TTSuV2.
      Phylogenetic analysis of TTSuV1 showed that 21 isolates were distributed into two
      clusters (genotype TTSuV1a and TTSuV1b), with genotype TTSuV1b was the dominant
      genotype. Phylogenetic analysis of TTSuV2 showed that the nine isolates shared
      80.9-99.2% nucleotide homology with each other, and were distributed in different
      genotypes (TTSuV2a-TTSuV2f). TTSuV2d was the most prevalent genotype in this
      study, which contained five Spanish strains and nine Chinese strains, and shared
      94.2-96.8% homology.

PMID- 22361030
TI  - Structure of the Vibrio cholerae Type IVb Pilus and stability comparison with the
      Neisseria gonorrhoeae type IVa pilus.
AB  - Type IV pili are multifunctional filaments displayed on many bacterial pathogens.
      Members of the Type IVa pilus subclass are found on a diverse group of human
      pathogens, whereas Type IVb pili are found almost exclusively on enteric
      bacteria. The Type IVa and IVb subclasses are distinguished by differences in the
      pilin subunits, including the fold of the globular domain. To understand the
      implications of the distinct pilin folds, we compared the stabilities of pilin
      subunits and pilus filaments for the Type IVa GC pilus from Neisseria gonorrhoeae
      and the Type IVb toxin-coregulated pilus (TCP) from Vibrio cholerae. We show that
      while recombinant TCP pilin is more stable than GC pilin, the GC pili are more
      resistant to proteolysis, heat and chemical denaturation than TCP, remaining
      intact in 8 M urea. To understand these differences, we determined the TCP
      structure by electron microscopy and three-dimensional image reconstruction. TCP
      have an architecture similar to that of GC pili, with subunits arranged in a
      right-handed 1-start helix and related by an 8.4-A axial rise and a 96.8 degrees 
      azimuthal rotation. However, the TCP subunits are not as tightly packed as GC
      pilins, and the distinct Type IVb pilin fold exposes a segment of the alpha
      helical core of TCP. Hydrophobic interactions dominate for both pilus subtypes,
      but base stacking by aromatic residues conserved among the Type IVa pilins may
      contribute to GC pilus stability. The extraordinary stability of GC pili may
      represent an adaptation of the Type IVa pili to harsh environments and the need
      to retract against external forces.

PMID- 22361034
TI  - A new formula for rapid assessment of pericardial effusion volume by computed
      tomography.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate a new formula for
      the rapid assessment of pericardial effusion (PE) volume by computed tomography.
      MATERIALS AND METHODS: Twenty computed tomographic scans positive for PE were
      reviewed by two observers. Diameters of PE were measured at four locations.
      Additionally, PE volume was assessed by volumetry. The correlation between PE
      diameters and volume was evaluated, and a linear equation was derived for each
      diameter location. To test validity and reliability of the measurements,
      intraclass correlation and Bland-Altman analysis were performed. RESULTS: Good
      validity was expressed by strong correlations between diameter measurements at
      all four locations and PE volume (all R values >0.80 and P values <.0001).
      Intraclass correlation (all coefficients >0.75) and Bland-Altman analysis
      revealed good interobserver and intraobserver reliability of diameter
      measurements. The best values were observed for apical diameter measurements. The
      following linear equation was derived for apical diameter measurements: PE volume
      = 296 (mL/cm) * apical diameter (cm) - 32 mL. CONCLUSIONS: PE volume can rapidly
      be assessed by apical PE diameter measurement using the simplified formula PE
      volume = 0.3 (L/cm) * apical diameter (cm).

PMID- 22361033
TI  - Assessing hepatomegaly: automated volumetric analysis of the liver.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to define volumetric
      nomograms for identifying hepatomegaly and to retrospectively evaluate the
      performance of radiologists in assessing hepatomegaly. MATERIALS AND METHODS:
      Livers were automatically segmented from 148 abdominal contrast-enhanced computed
      tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by
      visual inspection and/or linear liver height by radiologists). Quantified liver
      volumes were compared to manual measurements using volume overlap and error.
      Liver volumes were normalized to body surface area, from which hepatomegaly
      nomograms were defined (H scores) by analyzing the distribution of liver sizes in
      the healthy population. H scores were validated against consensus reports. The
      performance of radiologists in diagnosing hepatomegaly was retrospectively
      evaluated. RESULTS: The automated segmentation of livers was robust, with volume
      overlap and error of 96.2% and 2.2%, respectively. There were no significant
      differences (P > .10) between manual and automated segmentation for either the
      normal or the hepatomegaly subgroup. The average volumes of normal and enlarged
      livers were 1.51 +/- 0.25 and 2.32 +/- 0.75 L, respectively. One-way analysis of
      variance found that body surface area (P = .004) and gender (P = .02), but not
      age, significantly affected normal liver volume. No significant effects were
      observed for two-way and three-way interactions among the three variables (P >
      .18). H-score cutoffs of 0.92 and 1.08 L/m2 were used to define mild and massive
      hepatomegaly (95% confidence interval, +/- 0.02 L/m2). Using the H score as the
      reference standard, the sensitivity of radiologists in detecting all, mild, and
      massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity,
      respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31).
      The area under the receiver-operating characteristic curve of the H-score
      criterion for hepatomegaly detection was 0.98. CONCLUSIONS: Nomograms for the
      identification and grading of hepatomegaly from automatic volumetric liver
      assessment normalized to body surface area (H scores) are introduced. H scores
      match well with clinical interpretations for hepatomegaly and may improve
      hepatomegaly detection compared with height measurements or visual inspection,
      commonly used in current clinical practice.

PMID- 22361035
TI  - Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats
      by inhibiting protein oxidation and nitric oxide end products.
AB  - Chronic hyperglycemia in diabetes leads to free radicals overproduction, which
      contributes to the development of diabetic nephropathy. The present study
      investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae
      family, on renal impairment and oxidative stress in alloxan-induced diabetic
      rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg
      kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3
      weeks. Diabetic renal injury was associated with hyperglycemia, increased serum
      creatinine, urea and uric acid levels. This nephropathophysiology was associated
      with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced
      oxidation protein products (AOPP) levels and a decrease in glutathione (GSH)
      levels. In addition, hyperglycemia increased the activities of antioxidant
      enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione
      peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively
      ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative
      stress. Histological studies also supported the experimental findings. The
      results suggested that Ac might act as a beneficial agent against renal
      dysfunctions developed in alloxan-induced diabetes.

PMID- 22361036
TI  - Clinicopathologic features of the mixed epithelial and mesenchymal type
      metaplastic breast carcinoma with myoepithelial differentiation in a subset of
      six cases.
AB  - Metaplastic carcinoma (MC) of the breast, consisting of epithelial and mixed
      epithelial-mesenchymal tumors, are extremely rare human neoplasms. They are
      mostly detected between the 5th and 7th decade and have an unfavorable prognosis.
      Therefore, it is of utmost important to find out the behavior and also the
      immunohistochemical (IHC) profile of these tumors. In the current study, the aim
      was to examine 6 cases of MC with detailed clinico-pathological variables of
      cancer, follow-up and IHC profile of several antigens. The following
      immunohistochemical markers were used: MNF116, vimentin, CD10, smooth muscle
      actin (SMA), estrogen/progesterone receptors and HER-2/neu. The mean age was 39.1
      the mean size was 3.3 cm. 83% of the cases had spindle cell sarcoma-like areas.
      Two of six cases also had a chondrosarcoma-like component. The epithelial
      component was invasive ductal carcinoma in all. MNF116, vimentin, CD10, and SMA
      expressions were as follows: mesenchymal cells: 33%, 100%, 50%, 83%, epithelial
      cells: 100%, 50%, 33%, 0%. All were triple negative. 66.6% presented with the
      axillary lymph node metastases. The mean follow-up period was 51 months, 50% died
      of the disease. Two had distant metastases to the lung. Our series which only
      included mixed epithelial-mesenchymal type metaplastic carcinoma of the breast
      showed myoepithelial differentiation with a worse prognosis.

PMID- 22361037
TI  - Aberrant pattern of the cytokeratin 7/cytokeratin 20 immunophenotype in
      colorectal adenocarcinomas with BRAF mutations.
AB  - Cytokeratin 7 (CK7) and 20 (CK20) are used for the differential diagnosis of
      metastases from colorectal carcinomas (CRC), which are usually CK7-/CK20+, and
      other tumors. In our study, we performed immunohistochemical staining with CK7
      and CK20 in 52 randomly selected cases of CRC and analyzed microsatellite
      instability status and BRAF mutations to identify those factors that may
      determine the changing pattern of CK7/CK20 immunophenotype in these tumors. CK7
      was negative in all microsatellite stable tumors (MSS), but all carcinomas
      presenting microsatellite instability (MSI) and BRAF mutations were diffusely
      positive for this marker. CK20 was diffusely expressed in 79.06% of MSS tumors.
      Regarding MSI, in case with no BRAF mutations, a progressive decrease in CK20
      expression was noted, and in BRAF-mutated adenocarcinomas, no expression of CK20
      was observed. It seems that in case of MSI located on the proximal colon, which
      also presents BRAF mutations, CK20/CK7 may present a changing immunophenotype
      pattern, which may complicate the differential diagnosis of metastatic tumors.
      This is the first reported study of the relationship between CK20/CK7
      immunophenotype, BRAF mutations and microsatellite status in CRC.

PMID- 22361038
TI  - Molecular and morphological characterization of mealybugs (Hemiptera:
      Pseudococcidae) from Chilean vineyards.
AB  - Mealybugs are major pests of grapevines worldwide. They cause economic losses by
      lowering the cosmetic value of fruits, reducing yields, transmitting viruses and
      resulting in the quarantine or rejection of produce in international trade.
      Knowledge of the species present in a vineyard is important for the adjustment of
      management strategies. We surveyed and accurately characterized the mealybugs
      infesting vineyards in one of the main production areas of Chile; 164 mealybugs
      were sampled from 26 vineyards in four regions of Chile and identified by DNA
      sequencing for two markers (cytochrome oxidase I and internal transcribed spacer
      2) and morphological examination. Pseudococcus viburni (Signoret) was the most
      common species, followed by Pseudococcus meridionalis Prado and Pseudococcus
      cribata Gonzalez. Molecular variability at the COI and ITS2 loci was observed in
      both P. viburni and P. cribata. A comparison of haplotypes of P. viburni
      worldwide provides support for a recent hypothesis that this species is native to
      South America, a finding with direct consequences for management. Neither
      Pseudococcus longispinus (Targioni & Tozzetti) nor Planococcus ficus Signoret
      were found. 

PMID- 22361039
TI  - Relationship between treatment delay and final infarct size in STEMI patients
      treated with abciximab and primary PCI.
AB  - BACKGROUND: Studies on the impact of time to treatment on myocardial infarct size
      have yielded conflicting results. In this study of ST-Elevation Myocardial
      Infarction (STEMI) treated with primary percutaneous coronary intervention (PCI),
      we set out to investigate the relationship between the time from First Medical
      Contact (FMC) to the demonstration of an open infarct related artery (IRA) and
      final scar size.Between February 2006 and September 2007, 89 STEMI patients
      treated with primary PCI were studied with contrast enhanced magnetic resonance
      imaging (ceMRI) 4 to 8 weeks after the infarction. Spearman correlation was
      computed for health care delay time (defined as time from FMC to PCI) and
      myocardial injury. Multiple linear regression was used to determine covariates
      independently associated with infarct size. RESULTS: An occluded artery
      (Thrombolysis In Myocardial Infarction, TIMI flow 0-1 at initial angiogram) was
      seen in 56 patients (63%). The median FMC-to-patent artery was 89 minutes. There
      was a weak correlation between time from FMC-to-patent IRA and infarct size, r =
      0.27, p = 0.01. In multiple regression analyses, LAD as the IRA, smoking and an
      occluded vessel at the first angiogram, but not delay time, correlated with
      infarct size. CONCLUSIONS: In patients with STEMI treated with primary PCI we
      found a weak correlation between health care delay time and infarct size. Other
      factors like anterior infarction, a patent artery pre-PCI and effects of
      reperfusion injury may have had greater influence on infarct size than time-to
      treatment per se.

PMID- 22361040
TI  - The expression and prognostic significance of hepatoma-derived growth factor in
      oral cancer.
AB  - Hepatoma-derived growth factor (HDGF) participates in oncogenic progression and
      represents a prognostic factor in several types of cancer. This study aimed to
      elucidate the role of HDGF during oral carcinogenesis. HDGF expression and the
      tumorigenic behaviors in human oral cell lines were investigated by
      immunoblotting, invasion and colony formation assays. Recombinant adenovirus
      vectors were employed to modulate the HDGF level in oral cancer cells.
      Immunohistochemical analysis using tissue microarray (TMA) consisting of
      surgically resected samples from 95 oral cancer patients was performed to
      delineate the correlation between HDGF expression and clinic-pathological
      parameters. HDGF expression was higher in malignant oral cancer cells than benign
      ones. Adenovirus-mediated HDGF overexpression and knockdown demonstrated the
      cellular HDGF level regulated the tumorigenic behaviors of oral cancer cells.
      Immunohistochemical analysis revealed increased HDGF expression in the nucleus
      and cytoplasm in oral cancer tissues. The nuclear HDGF expression was
      significantly correlated with tumor stage (P=0.004) and grade (P=0.013) while the
      cytoplasmic HDGF expression was associated with tumor necrosis (P=0.002). Kaplan
      Meier analysis revealed that patients with high nuclear HDGF expression had
      significantly worse 5-year disease-specific survival (P=0.0069), metastasis-free
      survival (P=0.0168), and local recurrence-free survival (P=0.0047). Multivariate
      analysis indicated that the nuclear HDGF labeling index was an independent
      prognostic factor for disease-specific and local recurrence-free survival. HDGF
      overexpression contributes to the oncogenic processes in oral cancer cells and
      constitutes a novel prognostic factor for survival outcome of oral cancer
      patients.

PMID- 22361041
TI  - Management of chronic pain in a patient with autosomal dominant polycystic kidney
      disease by sequential celiac plexus blockade, radiofrequency ablation, and spinal
      cord stimulation.
AB  - Chronic pain frequently is associated with autosomal dominant polycystic kidney
      disease and is a significant cause of morbidity. The classic approach to treat
      pain in patients with this disease starts with nonpharmacologic therapy and
      progresses to high-dose opioid therapy and more invasive procedures, including
      surgery. We present the case of a 43-year-old white woman presenting in our
      clinic with poorly controlled chronic left flank and epigastric pain secondary to
      autosomal dominant polycystic kidney disease despite high-dose opioids and
      multiple cyst decompression procedures. After temporarily successful management
      with celiac plexus neurolysis and intercostal nerve radiofrequency ablations for
      years, the next more permanent step was dorsal column neurostimulation, affording
      excellent analgesia with significantly improved quality of life to this day.

PMID- 22361042
TI  - The US Food and Drug Administration's Risk Evaluation and Mitigation Strategy
      (REMS) program in practice: does it really inform patients and limit risk?

PMID- 22361043
TI  - Survival in patients treated by long-term dialysis compared with the general
      population.
AB  - BACKGROUND: Relative survival, a methodology previously used in epidemiologic
      studies of cancer, compares the observed survival of a patient cohort with
      expected survival derived from general population life tables. We examined
      relative survival in patients treated by long-term dialysis in the Italian
      Dialysis and Transplantation Registry in order to determine the prognosis of
      dialysis patients. STUDY DESIGN: Cohort study drawn from a registry. SETTING &
      PARTICIPANTS: Patients enrolled in the Italian Dialysis and Transplantation
      Registry. FACTORS: Sex, age, primary kidney disease, renal replacement therapy
      modality, and main comorbid conditions. OUTCOMES: Death from any cause.
      MEASUREMENTS: Relative survival ratio (the ratio of observed survival in the
      population of interest to the survival expected given the age- and period
      specific mortality of the general population) and excess mortality rate
      (difference between observed and expected mortality rates). RESULTS: In January
      2000 to December 2008, a total of 27,642 patients were included. The 5-year
      relative survival estimate was 55.6% (95% CI, 54.7%-56.5%). The excess mortality
      rate showed a peak at 3 months (21 deaths/100 patient-years), then decreased,
      becoming constant from the end of year 1 to year 8, with leveling off at about 10
      deaths/100 patient-years. Older age, systemic diseases, and diabetes showed the
      strongest association with excess mortality. Peritoneal dialysis was associated
      with a lower relative excess risk in only the first year of treatment.
      LIMITATIONS: The patient cohort comprises about half the Italian patients
      beginning dialysis therapy in the period. CONCLUSIONS: This study highlights the
      applicability of relative survival methods in dialysis patients. This measure
      allows estimation of disease prognosis and severity comparisons among chronic
      diseases. The excess mortality rate appears to be a more sensitive and
      informative measure than the simple proportion of survivors.

PMID- 22361044
TI  - Antimicrobial and physicochemical properties of experimental light curing
      composites with alkali-substituted calcium phosphate fillers.
AB  - OBJECTIVE: The antimicrobial and physicochemical properties of experimental light
      curing composites prepared with fillers made of mechanically activated alkali
      substituted calcium phosphates like CaKPO(4), CaNaPO(4) or Ca(2)KNa(PO(4))(2)
      were compared with a commercial silane-modified cristobalite filler. METHODS: The
      antimicrobial properties were tested using Streptococcus mutans, Staphylococcus
      aureus and a clinically isolated plaque mixture. The potential for reducing
      bacteria growth on modified composites was determined using the proliferation
      reagent WST-1, which enables the measurement of metabolic activity and therefore
      the colonization with living bacteria. Investigated material properties included
      the degree of conversion and a test of flexural strength. RESULTS: All alkali
      substituted composites provide a changed, mainly basic micro-milieu leading to a
      reduction of bacteria population with respect to the non-modified composite of
      about 25-70% with a flexural strength of cured composites in the range of 55-77
      MPa complying with the clinical standard and a degree of conversion of 44-66%.
      SIGNIFICANCE: This study suggests that the modified composites increase
      antimicrobial properties while basic composite characteristics are not influenced
      by the filler.

PMID- 22361045
TI  - [Increase in creatine phosphokinase and a suicide attempt during isotretinoin
      treatment].

PMID- 22361046
TI  - [Lactobezoar in clinical onset of diabetes mellitus type 1 with coeliac disease].

PMID- 22361047
TI  - [Are we prepared for a disaster? Spanish multicentre study].
AB  - INTRODUCTION: Paediatric Emergency Departments (PED) should have written disaster
      plans, to ensure a rapid and efficient response. OBJECTIVES: 1) to determine if
      Spanish PED have written disaster plans, 2) to describe the characteristics of
      these plans, and 3) if paediatric victims were included in them. MATERIAL AND
      METHODS: Descriptive multicentre study based on questionnaires sent to physicians
      in charge of different Spanish PED. The structured survey included questions
      about external emergency plans (EEP) and internal emergency plans (IEP). RESULTS:
      Twenty-five out of 44 surveys were replied. Eighteen PED had an EEP, most of them
      had been written 10 years ago and were reviewed every 3 years or more. In 11/18
      PED, the EEP was well-known by health care providers. Drills were never performed
      in 13/18 PED. Twenty-one PED had an IEP, most of them had been written 8 years
      ago and were reviewed every 3 years or more. In 13/21 PED, IEP was well-known by
      health care providers but drills were never performed in 12/21 PED. IEP included
      evacuation plans (22), fire emergency plans (19), bomb threat plan (13) and flood
      plans (9). Nine PED have paediatric-specific disaster plans and in 7 PED,
      disaster plans included adult and paediatric victims. Children were not included
      In 1 EEP and in 5 IEP. CONCLUSIONS: Most of PED have written disaster plans, but
      these plans are old, unknown by health care providers and almost half of them do
      not include paediatric victims. It is necessary to improve disaster planning in
      Spanish PED.

PMID- 22361048
TI  - [Percutaneous approach of a coronary fistulae with vascular plug].

PMID- 22361050
TI  - Influence of N deficiency and salinity on metal (Pb, Zn and Cu) accumulation and
      tolerance by Rhizophora stylosa in relation to root anatomy and permeability.
AB  - Effects of N deficiency and salinity on root anatomy, permeability and metal (Pb,
      Zn and Cu) translocation and tolerance were investigated using mangrove seedlings
      of Rhizophora stylosa. The results showed that salt could directly reduce radial
      oxygen loss (ROL) by stimulation of lignification within exodermis. N deficiency,
      oppositely, would reduce lignification. Such an alteration in root permeability
      may also influence metal tolerance by plants. The data indicated that a moderate
      salinity could stimulate a lignified exodermis that delayed the entry of metals
      into the roots and thereby contributed to a higher metal tolerance, while N
      deficiency would aggravate metal toxicity. The results from sand pot trail
      further confirmed this issue. This study provides a barrier property of the
      exodermis in dealing with environments. The plasticity of root anatomy is likely
      an adaptive strategy to regulate the fluxes of gases, nutrients and toxins at
      root-soil interface.

PMID- 22361049
TI  - Microglial TIR-domain-containing adapter-inducing interferon-beta (TRIF)
      deficiency promotes retinal ganglion cell survival and axon regeneration via
      nuclear factor-kappaB.
AB  - BACKGROUND: TIR-domain-containing adapter-inducing interferon-beta (TRIF) is the
      sole downstream adaptor of Toll-like receptor (TLR)3, which is one of the major
      signaling pathways in immune cells leading to neuroinflammation in the central
      nervous system. Overexpression of TRIF may lead to activation of inflammatory
      responses, and contribute to pathophysiological progression in both acute and
      chronic neurodegenerative retinal diseases. In the present study, was aimed to
      elucidate the contributions of TRIF to optic nerve (ON) regeneration and retinal
      ganglion cell (RGC) survival following injury to the ON, a widely studied model
      of central nervous system injury and of degenerative diseases such as glaucoma.
      METHODS: We used retrograde labeling with a fluorochrome, hydroxystilbamidine
      (Fluorogold) to evaluate RGC survival, and immunostaining with growth-associated
      protein-43 to evaluate axon regeneration in an ON crush model. Changes in
      microglial cytokines following RGC injury was examined with ELISA and real-time
      PCR. In vivo studies were carried out in wild-type and trif-/- mice. A Transwell
      co-culture system and migration test were used to mimic the crosstalk between
      microglia and RGCs. TRIF-associated downstream adaptors were determined by
      western blotting. RESULTS: Compared with wild-type (WT) mice, TRIF knockout (KO)
      mice displayed a robust ability to regenerate axons 3 or 7 days after nerve
      injury. In addition, RGC survival was considerably higher in trif-/- than in WT
      mice. ON lesion induced less microglial activation in trif-/- than in WT mice.
      and more WT microglia distorted and migrated toward the foramen opticum. In the
      transwell system, few trif-/- microglia migrated through the membrane when
      stimulated by the performed lesion on RGC axons in a transwell system.
      Inactivation of microglial cells in trif-/- mice was associated with reduced
      production of inflammatory cytokines, as detected with real-time RT-PCR and
      ELISA. Furthermore western blot analysis showed that activation of known
      downstream effectors of TRIF, including TBK1, IKKepsilon and NF-kappaB, were
      significantly inhibited by TRIF deficiency. CONCLUSION: Our results indicate that
      TRIF deficiency promotes ON axon regeneration by attenuating microglial
      activation and consequently reducing the release of harmful cytokines via NF
      kappaB inactivation.

PMID- 22361051
TI  - Rapid recovery of stem increment in Norway spruce at reduced SO2 levels in the
      Harz Mountains, Germany.
AB  - Tree-ring width of Picea abies was studied along an altitudinal gradient in the
      Harz Mountains, Germany, in an area heavily affected by SO(2)-related forest
      decline in the second half of the 20th century. Spruce trees of exposed high
      elevation forests had earlier been shown to have reduced radial growth at high
      atmospheric SO(2) levels. After the recent reduction of the SO(2) load due to
      clean air acts, we tested the hypothesis that stem growth recovered rapidly from
      the SO(2) impact. Our results from two formerly damaged high-elevation spruce
      stands support this hypothesis suggesting that the former SO(2)-related spruce
      decline was primarily due to foliar damage and not to soil acidification, as the
      deacidification of the (still acidic) soil would cause a slow growth response.
      Increasing temperatures and deposited N accumulated in the topsoil are likely
      additional growth-promoting factors of spruce at high elevations after the
      shortfall of SO(2) pollution.

PMID- 22361052
TI  - Stream habitat structure influences macroinvertebrate response to pesticides.
AB  - Agricultural pesticides continue to impair surface water ecosystems, although
      there are few assessments of interactions with other modifications such as fine
      sediment and physical alteration for flood drainage. We, therefore, surveyed
      pesticide contamination and macroinvertebrates in 14 streams along a gradient of
      expected pesticide exposure using a paired-reach approach to differentiate
      effects between physically modified and less modified sites. Apparent pesticides
      effects on the relative abundance of SPEcies At Risk (SPEAR) were increased at
      sites with degraded habitats primarily due to the absence of species with
      specific preferences for hard substrates. Our findings highlight the importance
      of physical habitat degradation in the assessment and mitigation of pesticide
      risk in agricultural streams.

PMID- 22361053
TI  - Analysis of quaternary ammonium compounds in urban stormwater samples.
AB  - A method for benzalkonium analysis has been developed to measure benzalkonium
      concentration in dissolved and particulate fractions from urban runoff samples.
      The analysis was performed by liquid chromatography coupled with mass
      spectrometry (LC-MS/MS). The dissolved matrix was extracted by Solid Phase
      Extraction (SPE), with cationic exchange and the particles by microwave
      extraction with acidified methanol. Recovery percentages were closed to 100% for
      benzalkonium C12 and C14. The protocol was applied to roof runoff samples
      collected after a roof demossing treatment, and to separative stormwater samples
      from a 200 ha catchment. The results illustrate an important contamination of the
      roof runoff, with a maximum concentration close to 27 mg/L during the first rain.
      The benzalkonium concentration (sum of C12 and C14) stayed high (up to 1 mg/L)
      even 5 months after the treatment. Benzalkonium concentration measured in
      stormwaters was low (0.2 MUg/L) but with contaminated suspended solids (up to 80
      MUg/g).

PMID- 22361054
TI  - Calibration and field performance of triolein embedded acetate membranes for
      passive sampling persistent organic pollutants in water.
AB  - Triolein embedded cellulose acetate membrane (TECAM) passive samplers provide
      potentially powerful tool for monitoring time weighted average concentrations
      (C(TWA)) of trace hydrophobic organic contaminants in water. To study the field
      performance of TECAM, exchange kinetics of chemicals between water and TECAM were
      studied at different temperature and water flow rates. Results showed that the
      uptake rate constant (k(u)) in TECAM was less sensitive to temperature variation
      than the SPMD and Chemcatcher. The k(u) in TECAM was sensitive to even a slight
      change of the flow rate, which required the field calibration using performance
      reference compounds (PRCs). To estimate C(TWA) by TECAM, both empirical model and
      WBL model were compared in laboratory conditions, and only small differences were
      observed between the predicted and measured k(u). Field validation was conducted
      to test the sampler performance alongside spot sampling. A good agreement of
      water concentration was obtained by the two sampling techniques.

PMID- 22361055
TI  - Toxicity of copper nanoparticles and CuCl2 salt to Enchytraeus albidus worms:
      survival, reproduction and avoidance responses.
AB  - Environmental effects of copper nanoparticles are little studied in terrestrial
      ecosystems. In the present article, the toxicity of copper nanoparticles (Cu-NP)
      on the enchytraeid Enchytraeus albidus is compared to the toxicity of a copper
      salt (CuCl(2)). The effect parameters studied were survival, reproductive output
      and avoidance behaviour. The results show that Cu-NP were more toxic to E.
      albidus than the same concentrations of the CuCl(2)-salt. The physic-chemical
      analysis of the particles indicated that only a small fraction was released as
      ions. Hence, the results indicated a nanoparticle-specific effect - lower
      reproductive output and higher avoidance. This was observed as 2-8 fold
      (significant) lower ECx values for Cu-NP (EC(50-reprod) = 95 mg Cu/kg; EC(50
      avoid) = 241 mg Cu/kg) exposed organisms compared to CuCl(2) (EC(50)(-)(reprod) =
      251 mg Cu/kg; EC(50-avoid) = 475 mg Cu/kg) exposed organisms. These results
      corroborate with a nanoparticle-specific effect.

PMID- 22361056
TI  - Effects of Tween 80 on the removal, sorption and biodegradation of pyrene by
      Klebsiella oxytoca PYR-1.
AB  - The sorption and biodegradation of pyrene by Klebsiella oxytoca PYR-1 (PYR-1) in
      the presence of nonionic surfactant Tween 80 were investigated toward a better
      understanding that how surfactants can affect biodegradation of hydrophobic
      organic compounds. The results indicated that Tween 80 can promote the removal,
      sorption and biodegradation of pyrene depending on the surfactant concentration,
      of which the most significant promotion of biodegradation was achieved at
      critical micelle concentration of Tween 80 with an improvement of 22.4%. A highly
      positive correlation (P<0.0001) was observed between the biodegradation and
      sorption of pyrene with the presence of Tween 80. Biosorption experiments showed
      the same trends as biodegradation and further illustrated the improved
      biodegradation of pyrene was mainly due to surfactant-facilitated sorption. The
      regularly changes of cell surface hydrophobicity suggested formation of more
      hydrophobic surface caused by surfactant sorption lead to stimulation of pyrene
      sorption.

PMID- 22361057
TI  - Column leaching of chromium and nickel from a contaminated soil using EDTA and
      citric acid.
AB  - This study investigates the column leaching of a soil contaminated mainly with Cr
      and Ni by using two chelants: citric acid (biodegradable) and EDTA (non
      biodegradable) followed with water rinse. The chelants lead to Cr and Ni
      leaching, in addition to major elements (Ca, Fe, Mg, Al, Mn and Zn) showing the
      dissolution of soil mineral constituents. EDTA leaches more major elements and Ni
      than citric acid related to the respective stability of metal-chelant complexes;
      citric acid leaches more Cr than EDTA, certainly because of a substitution
      reaction with Cr(VI). In the case of alternating chelant/water applications,
      leaching occurs during the chelant applications, but also during water
      applications. In the case of chelant/water applications followed by continuous
      water application, both Cr and Ni leach over time. This increased mobility could
      be due to the residual chelant present in soil as well as to the
      dissolution/mobilization of mineral or organic soil fractions.

PMID- 22361058
TI  - Proteomics to predict hepatitis C therapy outcome: where do we stand?

PMID- 22361059
TI  - Predictive scores for hepatocellular carcinoma development in chronic hepatitis B
      virus infection: "does one size fit all?".

PMID- 22361060
TI  - Role of autophagy in NOD2-induced inflammation in Crohn's disease.

PMID- 22361061
TI  - Influence of temperature on ischemic brain: basic and clinical principles.
AB  - In the last decades, the interest in the association between body temperature and
      stroke outcome has reemerged, and the use of animal models has made it possible
      to know the underlying pathogenic mechanisms involved, most of them with pending
      confirmation in human clinics. In this work, we will review the effects of
      hyperthermia and hypothermia and its pathogenesis on ischemic stroke, and the
      evidence of the efficacy and safety of anti-hyperthermic and hypothermic
      treatments. We will describe how treatment of hyperthermia on ischemic stroke
      patients, improves patient comfort and outcome, both in the short and the long
      term, but new clinical studies are needed in this field. Despite the theoretical
      and experimental bases in favor of hypothermia for the treatment of brain
      ischemia, there is no definitive clinical evidence that has proved its benefits,
      so far. With current knowledge, an objective of a body temperature between 35.5
      and 36.5  degrees C seems an optimal therapeutic target for both hyperthermic and
      normothermic patients.

PMID- 22361062
TI  - Vatalanib decrease the positive interaction of VEGF receptor-2 and P2X2/3
      receptor in chronic constriction injury rats.
AB  - Neuropathic pain can arise from a lesion affecting the peripheral nervous system.
      Selective P2X(3) and P2X(2/3) receptors' antagonists effectively reduce
      neuropathic pain. VEGF inhibitors are effective for pain relief. The present
      study investigated the effects of Vatalanib (VEGF receptor-2 (VEGFR-2) inhibitor)
      on the neuropathic pain to address the interaction of VEGFR-2 and P2X(2/3)
      receptor in dorsal root ganglia of chronic constriction injury (CCI) rats.
      Neuropathic pain symptoms following CCI are similar to most peripheral lesions as
      assessed by the Neuropathic Pain Symptom Inventory. Sprague-Dawley rats were
      randomly divided into sham group, CCI group and CCI rats treated with Vatalanib
      group. Mechanical withdrawal threshold and thermal withdrawal latency were
      measured. Co-expression of VEGFR-2 and P2X(2) or P2X(3) in L4-6 dorsal root
      ganglia (DRG) was detected by double-label immunofluorescence. The modulation
      effect of VEGF on P2X(2/3) receptor agonist-activated currents in freshly
      isolated DRG neurons of rats both of sham and CCI rats was recorded by whole-cell
      patch-clamp technique. The mechanical withdrawal threshold (MWT) and thermal
      withdrawal latency (TWL) in CCI group were lower than those in sham group
      (p<0.05). MWT and TWL in CCI rats treated with Vatalanib group were increased
      compared with those in CCI group (p<0.05). VEGFR-2 and P2X(2) or P2X(3) receptors
      were co-expressed in the cytoplasm and surface membranes of DRG. The co
      expression of VEGFR-2 and P2X(2) or P2X(3) receptor in CCI group exhibited more
      intense staining than those in sham group and CCI rats treated with Vatalanib
      group, respectively. VEGF enhanced the amplitude of ATP and alpha,beta-meATP 
      activated currents of both sham and CCI rats. Increment effects of VEGF on ATP
      and alpha,beta-meATP -activated currents in CCI rats were higher than those in
      sham rats. Both ATP (100 MUM) and alpha,beta-meATP (10 MUM)- activated currents
      enhanced by VEGF ( 1nM) were significantly blocked by Vatalanib (1 MUM, an
      inhibitor of VEGF receptors). The stain values of VEGFR-2, P2X(2) and P2X(3)
      protein expression in L4/5 DRG of CCI treated with Vatalanib group were
      significantly decreased compared with those in CCI group (p<0.01). Vatalanib can
      alleviate chronic neuropathic pain by decreasing the activation of VEGF on VEGFR
      2 and the positive interaction between the up-regulated VEGFR-2 and P2X(2/3)
      receptors in the neuropathic pain signaling.

PMID- 22361063
TI  - [Lung abscess and necrotizing pneumonia: chest tube insertion or surgery?].
AB  - Lung abscesses and necrotizing pneumonia are rare complications of community
      acquired pneumonia since the advent of antibiotics. Their management leans first
      of all on the antibiotic treatment adapted on the informed germs. However, in 11
      to 20% of the cases of lung abscesses, this treatment is insufficient, and
      drainage, either endoscopic or percutaneous, must be envisaged. In first
      intention, we shall go to less invasive techniques: endoscopic or percutaneous
      radio-controlled. In case of failure of these techniques, a percutaneous surgical
      drainage by minithoracotomy will be performed. In the necrotizing pneumonia,
      because of the joint obstruction of the bronchus and blood vessels corresponding
      to a lung segment, the systemic antibiotic treatment will be poor effective. In
      case of failure of this one we shall propose, a percutaneous surgical drainage,
      especially if the necrosis limits itself to a single lobe. The surgical treatment
      will be reserved: in the failures of the strategy of surgical drainage, in the
      necroses extending in several lobes.

PMID- 22361064
TI  - [Thoracic surgery in tuberculosis and non-tuberculous mycobacterial diseases].
AB  - Tuberculosis and non-tuberculous mycobacteria are common indications of pleural
      and mediastinal surgery on a diagnostic intend. However, parenchymatous resection
      on a curative intend has been proven to benefit to patients with multiresistant
      tuberculosis in adjunction with prolonged antibiotic treatment. Furthermore,
      tuberculosis sequelae, i.e. destroyed lung, Aspergillus-infected cavitary
      tuberculosis, and related hemoptysis are eradicated by a surgical management
      after careful medical preparation. Finally, surgical resection of localized
      Mycobacterium avium and M. xenopii infections is associated with a high rate of
      sputum conversion and a low morbidity.

PMID- 22361065
TI  - [Non-tumoral vascular disorders of the lung in the adulthood].
AB  - Non-tumoral vascular disorders of the lung are multiple, even if cases diagnosed
      in the adulthood are rare. They include congenital or acquired conditions, which
      related symptoms, if present, are non specific. This explains why their diagnosis
      is challenging and usually delayed. Surgery is the cornerstone of their
      treatment, although interventional radiology represents currently a less invasive
      alternative option for some of them.

PMID- 22361066
TI  - [Tracheobronchial and pulmonary parenchymatous congenital abnormalities requiring
      surgical treatment in adults].
AB  - Most tracheobronchial and parenchymatous congenital abnormalities of the
      respiratory system are diagnosed in early life. However, some lesions may be
      initially silent and diagnosed only in adulthood. These cases included congenital
      abnormalies of the tracheobronchial tract (tracheal and/or bronchial stenosis,
      bronchogenic cysts, bronchial atresia, oesotracheal fistula, oesobronchial
      fistula, and tracheal diverticulum), and lung parenchyma itself (pulmonary
      sequestration, congenital cystic adenomatoid malformation, lobar emphysema, lobar
      or lung hypoplasia). To avoid dreadful complications, these rare cases deserve
      surgical management, and must be known by chest physicians and surgeons.

PMID- 22361067
TI  - [Lung volume reduction surgery for emphysema and bullous pulmonary emphysema].
AB  - The improvement of respiratory symptoms for emphysematous patients by surgery is
      a concept that has evolved over time. Initially used for giant bullae, this
      surgery was then applied to patients with diffuse microbullous emphysema. The
      physiological and pathological concepts underlying these surgical procedures are
      the same in both cases: improve respiratory performance by reducing the high
      intrapleural pressure. The functional benefit of lung volume reduction surgery
      (LVRS) in the severe diffuse emphysema has been validated by the National
      Emphysema Treatment Trial (NETT) and the later studies which allowed to identify
      prognostic factors. The quality of the clinical, morphological and functional
      data made it possible to develop recommendations now widely used in current
      practice. Surgery for giant bullae occurring on little or moderately
      emphysematous lung is often a simpler approach but also requires specialised
      support to optimize its results.

PMID- 22361068
TI  - Evaluation of methane production and macronutrient degradation in the anaerobic
      co-digestion of algae biomass residue and lipid waste.
AB  - Algae biomass residue was co-digested with lipid-rich fat, oil, and grease waste
      (FOG) to evaluate the effect on methane yield and macronutrient degradation. Co
      digestion of algae biomass residue and FOG, each at 50% of the organic loading,
      allowed for an increased loading rate up to 3g VS/Ld, resulting in a specific
      methane yield of 0.54 L CH(4)/g VSd and a volumetric reactor productivity of 1.62
      L CH(4)/Ld. Lipids were the key contributor to methane yields, accounting for 68
      83% of the total methane potential. Co-digestion with algae biomass residue
      fractions of 33%, 50%, and 67% all maintained lipid degradations of at least 60%
      when the organic loading rate was increased to 3g VS/Ld, while synergetic effects
      on carbohydrate and protein degradation were less evident with increased loading.

PMID- 22361069
TI  - Membrane extraction for detoxification of biomass hydrolysates.
AB  - Membrane extraction was used for the removal of sulfuric acid, acetic acid, 5
      hydroxymethyl furfural and furfural from corn stover hydrolyzed with dilute
      sulfuric acid. Microporous polypropylene hollow fiber membranes were used. The
      organic extractant consisted of 15% Alamine 336 in: octanol, a 50:50 mixture of
      oleyl alcohol:octanol or oleyl alcohol. Rapid removal of sulfuric acid, 5
      hydroxymethyl and furfural was observed. The rate of acetic acid removal
      decreased as the pH of the hydrolysate increased. Regeneration of the organic
      extractant was achieved by back extraction into an aqueous phase containing NaOH
      and ethanol. A cleaning protocol consisting of flushing the hydrolysate
      compartment with NaOH and the organic phase compartment with pure organic phase
      enabled regeneration and reuse of the module. Ethanol yields from hydrolysates
      detoxified by membrane extraction using 15% Alamine 336 in oleyl alcohol were
      about 10% higher than those from hydrolysates detoxified using ammonium hydroxide
      treatment.

PMID- 22361070
TI  - A comprehensive life cycle assessment (LCA) of Jatropha biodiesel production in
      India.
AB  - A life cycle approach was adopted for energy, green house gas (GHG) emissions and
      renewability assessment for production of 1ton of Jatropha biodiesel. Allocation
      and displacement approaches were applied for life cycle inventory, process energy
      and process GHG emission attribution to co-products. The results of process
      energy and GHG emission analyses revealed that the amount of process energy
      consumption and GHG emission in the individual stages of the life cycle
      assessment (LCA) were a strong function of co-product handling and irrigation.
      The GHG emission reduction with respect to petroleum diesel for generating 1GJ
      energy varied from 40% to 107% and NER values from 1.4 to 8.0 depending upon the
      methodology used for energy and emission distribution between product and co
      products as well as irrigation applied. However, GHG emission reduction values of
      54 and 40 and NER (net energy ratio) values of 1.7 and 1.4 for irrigated and rain
      fed scenarios, respectively indicate the eco-friendly nature and renewability of
      biodiesel even in the worst scenario where total life cycle inventory (LCI),
      process energy and GHG emission were allocated to biodiesel only.

PMID- 22361071
TI  - Application of air-cathode pipe reactor to simultaneously suppress sulphate
      reduction and accelerate COD oxidation in synthetic wastewater.
AB  - While bio-corrosion causes severe damage to sewer pipeline, removal of organics
      in wastewater treatment plants consume substantial energy and is costly.
      Accepting the electrons from degrading organics by sulphate will produce sulphide
      - the culprit of corrosion. In this experiment, electrodes were tested for its
      ability to reduce sulphide formation by transferring electrons to outside the
      water. Two bench-scale pipe reactors, one with and the other without electrodes
      were fed with acetate based synthetic wastewater (800 mg/l COD) and sulphate (39
      mg/l). In all cases, electrodes were found to suppress sulphate reduction; for
      low sulphate feed, the average reduction was 2 compared to 4 mg/l and for high
      sulphate feed it was 20 compared to 68 mg/l. In addition electrodes assisted
      higher COD removal; the average removal during low sulphate feed was 200 compared
      to 300 mg/l, but during high sulphate feed they were 300 compared to 450 mg/l.

PMID- 22361072
TI  - Enzyme-assisted extraction of lipids directly from the culture of the oleaginous
      yeast Rhodosporidium toruloides.
AB  - Lipids produced by oleaginous microorganisms are a potential feedstock for
      biodiesel production and chemical synthesis. Yet, the costs of microbial lipids
      remain high, partially because the lipid recovery process is tedious and costly.
      In the present study, enzyme-assisted extraction of lipids from the culture of
      the yeast Rhodosporidium toruloides was carried out. With a heat pre-treatment
      with microwave, enzymatic treatment with the recombinant beta-1,3-glucomannanase,
      plMAN5C, and extraction with ethyl acetate, 96.6% of the total lipids were
      extracted from R. toruloides cells at room temperature and atmospheric pressure
      directly from the culture without dewatering. Therefore, this process could
      significantly reduce energy consumption and costs for lipids extraction from the
      yeast.

PMID- 22361073
TI  - Enhanced growth and lipid production of microalgae under mixotrophic culture
      condition: effect of light intensity, glucose concentration and fed-batch
      cultivation.
AB  - Microalgae capable of accumulating high lipid content were screened in
      photoautotrophic, heterotrophic and mixotrophic cultures. The biomass and lipid
      production of all tested strains in mixotrophic culture were notably enhanced in
      comparison with photoautotrophic and heterotrophic cultures. Among the tested
      strains, marine Chlorella sp. and Nannochloropsis sp. were ideal candidates for
      biodiesel production because of their high lipid production. The influence of
      light intensity and initial glucose concentration on growth and lipid content of
      both strains were investigated. Although increasing light intensity and initial
      glucose concentration enhanced the growth of both strains, it reduced their lipid
      content. To produce a high amount of biomass with high lipid content, a fed-batch
      cultivation with stepwise increasing light intensity was performed. The lipid
      production by this strategy was approximately twice that of conventional batch
      cultivation. The main fatty acid compositions of the two microalgae were C16-C18
      (>80%) which are appropriate for biodiesel production.

PMID- 22361074
TI  - Treatment of saline wastewater by a sequencing batch reactor with emphasis on
      aerobic granule formation.
AB  - The formation and characteristics of aerobic granules in a sequencing batch
      reactor (SBR), designed to treat saline wastewater, have been investigated in
      this study. Granule structure was determined using scanning electron microscope
      (SEM), and polymerase chain reaction (PCR). Granules formed in the reactors were
      grouped into light brown granules and black granules that looked 'fluffy'. The
      first group was more dense than the second group and consequently had a higher
      settling velocity. The densities of the first and the second group were 0.056 and
      0.035 g/ml, respectively. While the corresponding settling velocity were 1.35 and
      0.97 cm/s, respectively. The kinetic coefficients K(s), k(d), k and Y in saline
      substrate (10 g NaCl/l) were estimated to be 195 mg s COD/l, 0.025 g VSS/g VSS d,
      2.29 g s COD/g VSS d and 0.45 mg VSS/mg s COD, respectively. Analysis of granules
      using 16S rDNA sequences showed that the dominant microbial species was
      Klebsiella oxitoca. Minerals and the protozoan community in saline substrate
      facilitated the formation of granules. It was concluded that the fluffy granules
      are a variation of the light brown granules which are resistant to salt.

PMID- 22361075
TI  - Simultaneous saccharification and co-fermentation (SSCF) of AFEX(TM) pretreated
      corn stover for ethanol production using commercial enzymes and Saccharomyces
      cerevisiae 424A(LNH-ST).
AB  - Xylose consumption by Saccharomyces cerevisiae 424A(LNH-ST) during simultaneous
      saccharification and co-fermentation (SSCF) of AFEX(TM) pretreated switchgrass
      was inhibited by unhydrolyzed solids. Such inhibitory effects were not found in
      unhydrolyzed solids from AFEX(TM) pretreated corn stover (AFEX(TM)-CS). However,
      the xylose consumption was still unsatisfactory during 6h pre-hydrolysis SSCF. By
      extending the pre-hydrolysis time to 24h or longer, the xylose consumption was
      improved significantly. In order to better understand the reasons for such
      improvement, the hydrolysate slurries after 6h pre-hydrolysis and 24h pre
      hydrolysis were studied and compared. We found that the glucose concentration
      after pre-hydrolysis was the critical factor that determined cell viability and
      hence xylose consumption during SSCF. Low temperature (30 degrees C) and ethanol
      inhibition were shown to be the factors limiting hydrolysis rate and hence
      productivity during SSCF.

PMID- 22361076
TI  - Hierarchical organization of gamma and theta oscillatory dynamics in
      schizophrenia.
AB  - BACKGROUND: Schizophrenia patients have deficits across a broad range of
      important cognitive and clinical domains. Synchronization of oscillations in the
      gamma frequency range (~40 Hz) is associated with many normal cognitive functions
      and underlies at least some of the deficits observed in schizophrenia patients.
      Recent studies have demonstrated that gamma oscillations are modulated by the
      phase of theta waves, and this cross-frequency coupling indicates that a complex
      and hierarchical organization governs neural oscillatory dynamics. The aims of
      the present study were to determine if schizophrenia patients have abnormalities
      in the amplitude, synchrony, and cross-frequency coupling of gamma and theta
      oscillations in response to gamma-frequency steady-state stimulation and if
      abnormal neural oscillatory dynamics are associated with cognitive deficits in
      schizophrenia. METHODS: Schizophrenia patients (n = 234) and healthy control
      subjects (n = 188) underwent electroencephalography testing in response to 40-Hz
      auditory steady-state stimulation. Cognitive functions were assessed with a
      battery of neuropsychological tests. RESULTS: Schizophrenia patients had
      significantly reduced gamma intertrial phase coherence, increased theta
      amplitude, and intact cross-frequency coupling relative to healthy control
      subjects. In schizophrenia patients, increased theta amplitude was associated
      with poor verbal memory performance. CONCLUSIONS: Results suggest that
      schizophrenia patients have specific alterations in both gamma and theta
      oscillations, but these deficits occur in the context of an intact hierarchical
      organization of their cross-frequency modulation in response to 40-Hz steady
      state stimulation. Cortical oscillatory dynamics may be useful for understanding
      the neural mechanisms that underlie the disparate cognitive and functional
      impairments of schizophrenia.

PMID- 22361078
TI  - Presence of atrial fibrillation is independently associated with adverse outcomes
      in patients hospitalized with heart failure: an analysis of get with the
      guidelines-heart failure.
AB  - BACKGROUND: It is unclear if the presence of atrial fibrillation (AF) on
      admission is associated with worse in-hospital outcomes in patients hospitalized
      with heart failure (HF). This study evaluated the clinical characteristics,
      management, length of stay, and mortality of HF patients with and without AF.
      METHODS AND RESULTS: We studied 99 810 patients from 255 sites admitted with HF
      enrolled in Get With The Guidelines-Heart Failure between January 1, 2005, and
      December 31, 2010. Patients with AF on admission were compared with patients in
      sinus rhythm. A total of 31 355 (31.4%) HF patients presented with AF, of which
      6701 (21.3%) were newly diagnosed. Patients in AF were older (77+/-12 versus 70+/
      15, P<0.001) and were more likely to have history of stroke and valvular heart
      disease. AF patients had higher B-type natriuretic peptide levels and ejection
      fraction (42+/-17% versus 39+/-17%, P<0.001). AF patients were more likely to be
      hospitalized >4 days (48.8% versus 41.5%, P<0.001), discharged to a facility
      other than home (28.5% versus 19.7%, P<0.001), and had higher hospital mortality
      rate (4.0% versus 2.6%, P<0.001). AF, particularly newly diagnosed, was
      independently associated with adverse outcomes (adjusted odds ratios and 95%
      confidence intervals for mortality 1.17, 1.05-1.29, P=0.0029, and 1.29, 1.10
      1.52, P=0.0023 for AF and newly diagnosed AF, respectively). CONCLUSIONS: In
      patients hospitalized with HF, AF is present in one-third and is independently
      associated with adverse hospital outcomes and longer length of stay. Whether
      prompt restoration of sinus rhythm would improve outcomes in patients
      hospitalized with HF and new-onset or paroxysmal AF is unclear and requires
      further study.

PMID- 22361077
TI  - T lymphocytes and vascular inflammation contribute to stress-dependent
      hypertension.
AB  - BACKGROUND: Psychological stress is a significant risk factor for hypertension
      and also directly affects the immune system. We have previously reported that T
      lymphocytes are essential for development of hypertension and that the central
      nervous system contributes to peripheral T-lymphocyte activation and vascular
      inflammation in this disease; however, the role of T-cell activation in stress
      related hypertension remains unclear. METHODS: Wild-type and T-cell-deficient
      (RAG-1(-/-)) mice were subjected to daily episodes of stress and blood pressure
      was measured. Circulating T-cell activation markers and vascular infiltration of
      immune cells were analyzed, as were stress hormone levels and gene expression
      changes in the brain. The effects angiotensin II infusion in the presence of
      chronic stress was also studied. RESULTS: Repeated daily stress contributed to
      acute elevations in blood pressure that were associated with increased activation
      of circulating T cells and increased vascular infiltration of T cells. Repeated
      stress increased blood pressure in wild-type but not RAG-1(-/-) mice. Adoptive
      transfer of T cells to RAG-1(-/-) mice restored blood pressure elevation in
      response to stress. Stress-related hypertension and vascular infiltration of T
      cells was markedly enhanced by angiotensin II. Moreover, angiotensin II-infused
      mice exposed to chronic stress exhibited greater blood pressure reactivity to an
      episode of acute stress. CONCLUSIONS: These data demonstrate that stress
      dependent hypertension triggers an inflammatory response that raises blood
      pressure at baseline and augments the hypertension caused by angiotensin II.
      These data provide insight as to how psychological stress contributes to
      hypertension.

PMID- 22361079
TI  - Multiple biomarkers for risk prediction in chronic heart failure.
AB  - BACKGROUND: Prior studies have suggested using a panel of biomarkers that measure
      diverse biological processes as a prognostic tool in chronic heart failure.
      Whether this approach improves risk prediction beyond clinical evaluation is
      unknown. METHODS AND RESULTS: In a multicenter cohort of 1513 chronic systolic
      heart failure patients, we measured a contemporary biomarker panel consisting of
      high-sensitivity C-reactive protein, myeloperoxidase, B-type natriuretic peptide,
      soluble fms-like tyrosine kinase receptor-1, troponin I, soluble toll-like
      receptor-2, creatinine, and uric acid. From this panel, we calculated a
      parsimonious multimarker score and assessed its performance in predicting risk of
      death, cardiac transplantation, or ventricular assist device placement in
      comparison to an established clinical risk score, the Seattle Heart Failure Model
      (SHFM). During a median follow-up of 2.5 years, there were 317 outcomes: 187
      patients died; 99 were transplanted; and 31 had a ventricular assist device
      placed. In unadjusted Cox models, patients in the highest tertile of the
      multimarker score had a 13.7-fold increased risk of adverse outcomes compared
      with the lowest tertile (95% confidence interval, 8.75-21.5). These effects were
      independent of the SHFM (adjusted hazard ratio, 6.80; 95% confidence interval,
      4.18-11.1). Addition of the multimarker score to the SHFM led to a significantly
      improved area under the receiver operating characteristic curve of 0.803 versus
      0.756 (P=0.003) and appropriately reclassified a significant number of patients
      who had the outcome into a higher risk category (net reclassification
      improvement, 25.2%; 95% confidence interval, 14.2-36.2%; P<0.001). CONCLUSIONS:
      In ambulatory chronic heart failure patients, a score derived from multiple
      biomarkers integrating diverse biological pathways substantially improves
      prediction of adverse events beyond current metrics.

PMID- 22361080
TI  - Phase II study to assess the efficacy of hypofractionated stereotactic
      radiotherapy in patients with large cavernous sinus hemangiomas.
AB  - PURPOSE: Cavernous sinus hemangioma is a rare vascular tumor. The direct
      microsurgical approach usually results in massive hemorrhage. Although
      radiosurgery plays an important role in managing cavernous sinus hemangiomas as a
      treatment alternative to microsurgery, the potential for increased toxicity with
      single-session treatment of large tumors is a concern. The purpose of this study
      was to assess the efficacy of hypofractionated stereotactic radiotherapy in
      patients with large cavernous sinus hemangiomas. METHODS: Fourteen patients with
      large (volume >20 cm(3)) cavernous sinus hemangiomas were enrolled in a
      prospective Phase II study between December 2007 and December 2010. The
      hypofractionated stereotactic radiotherapy dose was 21 Gy delivered in 3
      fractions. RESULTS: After a mean follow-up of 15 months (range, 6-36 months), the
      magnetic resonance images showed a mean of 77% tumor volume reduction (range, 44
      99%). Among the 6 patients with cranial nerve impairments before hypofractionated
      stereotactic radiotherapy, 1 achieved symptomatic complete resolution and 5 had
      improvement. No radiotherapy-related complications were observed during follow
      up. CONCLUSION: Our current experience, though preliminary, substantiates the
      role of hypofractionated stereotactic radiotherapy for large cavernous sinus
      hemangiomas. Although a longer and more extensive follow-up is needed,
      hypofractionated stereotactic radiotherapy of 21 Gy delivered in 3 fractions is
      effective in reducing the tumor volume without causing any new deficits and can
      be considered as a treatment modality for large cavernous sinus hemangiomas.

PMID- 22361081
TI  - Local control, toxicity, and cosmesis in women >70 years enrolled in the American
      Society of Breast Surgeons accelerated partial breast irradiation registry trial.
AB  - PURPOSE: The American Society of Breast Surgeons enrolled women in a registry
      trial to prospectively study patients treated with the MammoSite Radiation
      Therapy System breast brachytherapy device. The present report examined the
      outcomes in women aged >70 years enrolled in the trial. METHODS AND MATERIALS: A
      total of 1,449 primary early stage breast cancers were treated in 1,440 women. Of
      these, 537 occurred in women >70 years old. Fisher's exact test was performed to
      correlate age (<= 70 vs. >70 years) with toxicity and with cosmesis. The
      association of age with local recurrence (LR) failure times was investigated by
      fitting a parametric model. RESULTS: Older women were less likely to develop
      telangiectasias than younger women (7.9% vs. 12.4%, p = 0.0083). The incidence of
      other toxicities was similar. Cosmesis was good or excellent in 92% of the women
      >70 years old. No significant difference was found in LR as a function of age.
      The 5-year actuarial LR rate with invasive disease for the older vs. younger
      population was 2.79% and 2.92%, respectively (p = 0.5780). In women >70 years
      with hormone-sensitive tumors <= 2 cm who received hormonal therapy (n = 195),
      the 5-year actuarial rate of LR, overall survival, disease-free survival, and
      cause-specific survival was 2.06%, 89.3%, 87%, and 97.5%, respectively. These
      outcomes were similar in women who did not receive hormonal therapy. Women with
      small, estrogen receptor-negative disease had worse LR, overall survival, and
      disease-free survival compared with receptor-positive patients. CONCLUSIONS:
      Accelerated partial breast irradiation with the MammoSite radiation therapy
      system resulted in low toxicity and produced similar cosmesis and local control
      at 5 years in women >70 years compared with younger women. This treatment should
      be considered as an alternative to omitting adjuvant radiotherapy for older women
      with small-volume, early-stage breast cancer.

PMID- 22361082
TI  - Salvage treatment for recurrent intracranial germinoma after reduced-volume
      radiotherapy: a single-institution experience and review of the literature.
AB  - PURPOSE: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT).
      However, recurrence still occurs, especially when limited-field RT is applied,
      and the optimal salvage therapy remains controversial. METHODS AND MATERIALS:
      Between January 1989 and December 2010, 14 patients with clinically or
      pathologically diagnosed recurrent IGs after RT were reviewed at our institution.
      Of these, 11 received focal-field RT, and the other 3 received whole-brain
      irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the
      respective first course of RT. In addition, we identified from the literature 88
      patients with recurrent IGs after reduced-volume RT, in whom the details of
      salvage therapy were recorded. RESULTS: The median time to recurrence was 30.3
      months (range, 3.8-134.9 months). One patient did not receive further treatment
      and was lost during follow-up. Of the patients, 7 underwent salvage with
      craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with
      whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median
      follow-up time was 105.1 months (range, 24.2-180.9 months). Three patients died
      without evidence of disease progression: two from second malignancies and one
      from unknown cause. The others remained disease free. The 3-year survival rate
      after recurrence was 83.3%. A total of 102 patients from our study and the
      literature review were analyzed to determine the factors affecting prognosis and
      outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all
      patients and for those receiving salvage CSI, respectively. Univariate analysis
      showed that initial RT volume, initial RT dose, initial CT, and salvage RT type
      were significant prognostic predictors of survival. On multivariable analysis,
      salvage CSI was the most significant factor (p = 0.03). CONCLUSIONS: Protracted
      follow-up is recommended because late recurrence is not uncommon. CSI with or
      without CT is an effective salvage treatment for recurrence after reduced-volume
      RT.

PMID- 22361083
TI  - Volume changes after stereotactic LINAC radiotherapy in vestibular schwannoma:
      control rate and growth patterns.
AB  - PURPOSE: The purpose of this study was to evaluate the control rate of vestibular
      schwannomas (VS) after treatment with linear accelerator (LINAC)-based
      stereotactic radiosurgery (SRS) or radiotherapy (SRT) by using a validated
      volumetric measuring tool. Volume-based studies on prognosis after LINAC-based
      SRS or SRT for VS are reported scarcely. In addition, growth patterns and risk
      factors predicting treatment failure were analyzed. MATERIALS AND METHODS:
      Retrospectively, 37 VS patients treated with LINAC based SRS or SRT were
      analyzed. Baseline and follow-up magnetic resonance imaging scans were analyzed
      with volume measurements on contrast enhanced T1-weighted magnetic resonance
      imaging. Absence of intervention after radiotherapy was defined as "no additional
      intervention group, " absence of radiological growth was defined as "radiological
      control group. " Significant growth was defined as a volume change of 19.7% or
      more, as calculated in a previous study. RESULTS: The cumulative 4-year
      probability of no additional intervention was 96.4% +/- 0.03; the 4-year
      radiological control probability was 85.4% +/- 0.1). The median follow-up was 40
      months. Overall, shrinkage was seen in 65%, stable VS in 22%, and growth in 13%.
      In 54% of all patients, transient swelling was observed. No prognostic factors
      were found regarding VS growth. Previous treatment and SRS were associated with
      transient swelling significantly. CONCLUSIONS: Good control rates are reported
      for LINAC based SRS or SRT in VS, in which the lower rate of radiological growth
      control is attributed to the use of the more sensitive volume measurements.
      Transient swelling after radiosurgery is a common phenomenon and should not be
      mistaken for treatment failure. Previous treatment and SRS were significantly
      associated with transient swelling.

PMID- 22361084
TI  - Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate
      cancer treated with radiotherapy.
AB  - PURPOSE: To predict the grade and incidence of late clinical rectal toxicity
      through short-term (1 year) mucosal alterations. METHODS AND MATERIALS: Patients
      with prostate adenocarcinoma treated with curative or adjuvant radiotherapy
      underwent proctoscopy a year after the course of radiotherapy. Mucosal changes
      were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were
      analyzed according to the Kaplan-Meier method. Comparison between prognosis
      groups was performed by log-rank analysis. RESULTS: After a median follow-up time
      of 45 months (range, 18-99), the 3-year incidence of grade >= 2 rectal late
      toxicity according to the criteria of the European Organization for Research and
      Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all
      patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade >= 2
      clinical rectal late toxicity was higher in patients with grade >= 2 (32% vs. 15
      %, p = 0.02) or grade >= 3 VRS telangiectasia (47% vs. 17%, p <= 0.01) and an
      overall VRS score of >= 2 (31% vs. 16 %, p = 0.04) or >= 3 (48% vs. 17%, p =
      0.01) at the 1-year proctoscopy. CONCLUSIONS: Early proctoscopy (1 year) predicts
      late rectal bleeding and therefore can be used as a surrogate endpoint for late
      rectal toxicity in studies aimed at reducing this frequent complication.

PMID- 22361086
TI  - Cost comparison of nephron-sparing treatments for cT1a renal masses.
AB  - OBJECTIVES: Treatment options for small renal tumors have evolved from radical
      nephrectomy (RN) to partial nephrectomy (PN), thermal ablation, or active
      surveillance. With the advancement of techniques, costs differences are unclear.
      The objective of this study is to compare the 6-month costs associated with
      nephron-sparing procedures for cT1a renal tumors. MATERIALS AND METHODS: We
      performed a review of patients diagnosed with a solitary cT1a renal mass who
      underwent surgical treatment from June 2008 to May 2011. Open partial nephrectomy
      (OPN), robot-assisted partial nephrectomy (RLPN), laparoscopic radio-frequency
      ablation (LRFA), or computed tomography guided radio frequency ablation (CTRFA)
      was performed on 173 patients. Cost data were collected for surgical costs,
      associated hospital stay, and the 6-month postoperative period. RESULTS: Patients
      underwent surgery, including 52 OPN, 48 RLPN, 44 LRFA, and 29 CTRFA. Median total
      costs associated were $17,018, $20,314, $13,965, and $6,475, for OPN, RLPN, LRFA,
      and CTRFA, respectively. When stratified by approach differences were noted for
      total cost (P < 0.001), operating room (OR) time (P < 0.001), surgical supply (P
      < 0.001), and room and board (P < 0.001) in univariable analysis. Multivariable
      linear regression (R(2) = 0.966) showed surgical approach (P = 0.007), length of
      stay (P < 0.001), and OR time (P < 0.001) to be significant predictors of total
      cost. However, tumor size (P = 0.175), and Charlson comorbidity index (P = 0.078)
      were not statistically significant. CONCLUSIONS: Six-month cost of nephron
      sparing surgery is lowest with radio frequency ablation (RFA) by either
      laparoscopic or computed tomography (CT)-guided approach compared to RLPN and
      OPN. As oncologic and safety outcomes improve and become comparable in all
      nephron-sparing surgery (NSS) approaches, cost of each procedure will start to
      play a stronger role in the clinical and healthcare policy setting.

PMID- 22361085
TI  - A quality assurance method that utilizes 3D dosimetry and facilitates clinical
      interpretation.
AB  - PURPOSE: To demonstrate a new three-dimensional (3D) quality assurance (QA)
      method that provides comprehensive dosimetry verification and facilitates
      evaluation of the clinical significance of QA data acquired in a phantom. Also to
      apply the method to investigate the dosimetric efficacy of base-of-skull (BOS)
      intensity-modulated radiotherapy (IMRT) treatment. METHODS AND MATERIALS: Two
      types of IMRT QA verification plans were created for 6 patients who received BOS
      IMRT. The first plan enabled conventional 2D planar IMRT QA using the Varian
      portal dosimetry system. The second plan enabled 3D verification using an
      anthropomorphic head phantom. In the latter, the 3D dose distribution was
      measured using the DLOS/Presage dosimetry system (DLOS = Duke Large-field-of-view
      Optical-CT System, Presage Heuris Pharma, Skillman, NJ), which yielded isotropic
      2-mm data throughout the treated volume. In a novel step, measured 3D dose
      distributions were transformed back to the patient's CT to enable calculation of
      dose-volume histograms (DVH) and dose overlays. Measured and planned patient DVHs
      were compared to investigate clinical significance. RESULTS: Close agreement
      between measured and calculated dose distributions was observed for all 6 cases.
      For gamma criteria of 3%, 2 mm, the mean passing rate for portal dosimetry was
      96.8% (range, 92.0%-98.9%), compared to 94.9% (range, 90.1%-98.9%) for 3D. There
      was no clear correlation between 2D and 3D passing rates. Planned and measured
      dose distributions were evaluated on the patient's anatomy, using DVH and dose
      overlays. Minor deviations were detected, and the clinical significance of these
      are presented and discussed. CONCLUSIONS: Two advantages accrue to the methods
      presented here. First, treatment accuracy is evaluated throughout the whole
      treated volume, yielding comprehensive verification. Second, the clinical
      significance of any deviations can be assessed through the generation of DVH
      curves and dose overlays on the patient's anatomy. The latter step represents an
      important development that advances the clinical relevance of complex treatment
      QA.

PMID- 22361087
TI  - Frozen section pathology at time of hysterectomy accurately predicts endometrial
      cancer in patients with preoperative diagnosis of atypical endometrial
      hyperplasia.
AB  - OBJECTIVES: A significant number of women diagnosed with atypical endometrial
      hyperplasia (AEH) on endometrial biopsy will be diagnosed with endometrial cancer
      (EC) on the hysterectomy specimen at permanent section. Surgical treatment for
      AEH and EC differ substantially. We have assessed the concordance in EC between
      frozen and permanent sections on patients undergoing hysterectomy for AEH.
      MATERIALS AND METHODS: A retrospective review of 66 frozen sections on patients
      undergoing hysterectomy for AEH was performed. Frozen and permanent section
      diagnoses were categorized as negative or positive for malignancy. Permanent
      section carcinomas were classified as low or high risk based on their
      histopathology, myometrial invasion and differentiation. Correlation between
      frozen and permanent section and sensitivity, specificity, PPV, NPV and accuracy
      of frozen section in predicting EC in permanent section were calculated.
      Likelihood of diagnosing EC on frozen section was compared based on risk
      stratification at permanent section. RESULTS: Frozen and permanent sections
      revealed malignancy in 43.9% and 56% of the patients respectively. 94.1% of high
      risk carcinomas were identified as EC at frozen section as compared to 55% of low
      risk EC. Concordance was good (kappa=0.75). Sensitivity, specificity, NPV, PPV
      and accuracy in predicting EC at frozen section were 73%, 93.1%, 73% and 93.1%
      respectively. Carcinomas were detected at frozen section significantly more often
      if they were at high risk. CONCLUSIONS: The substantial agreement between frozen
      and permanent sections allows minimizing under- and overtreatment of women
      undergoing hysterectomy for AEH. High risk EC are efficiently identified in
      frozen section.

PMID- 22361088
TI  - Gender-based violence and socioeconomic inequalities: does living in more
      deprived neighbourhoods increase women's risk of intimate partner violence?
AB  - This study investigates the influence of neighbourhood socioeconomic conditions
      on women's likelihood of experiencing intimate partner violence (IPV) in Sao
      Paulo, Brazil. Data from 940 women who were interviewed as part of the WHO multi
      country study on women's health and domestic violence against women, and census
      data for Sao Paulo City, were analyzed using multilevel regression techniques. A
      neighbourhood socioeconomic-level scale was created, and proxies for the
      socioeconomic positions of the couple were included. Other individual level
      variables included factors related to partner's behaviour and women's experiences
      and attitudes. Women's risk of IPV did not vary across neighbourhoods in Sao
      Paulo nor was it influenced by her individual socioeconomic characteristics.
      However, women in the middle range of the socioeconomic scale were significantly
      more likely to report having experienced violence by a partner. Partner
      behaviours such as excessive alcohol use, controlling behaviour and multiple
      sexual partnerships were important predictors of IPV. A women's likelihood of IPV
      also increased if either her mother had experienced IPV or if she used alcohol
      excessively. These findings suggest that although the characteristics of people
      living in deprived neighbourhoods may influence the probability that a woman will
      experience IPV, higher-order contextual dynamics do not seem to affect this risk.
      While poverty reduction will improve the lives of individuals in many ways,
      strategies to reduce IPV should prioritize shifting norms that reinforce certain
      negative male behaviours.

PMID- 22361089
TI  - Aspirin use and cardiovascular events in social networks.
AB  - We tested whether friends' and family members' cardiovascular health events and
      also their own aspirin use are associated with the likelihood that an individual
      takes aspirin regularly. Analyses were based on longitudinal data on 2724 members
      of the Framingham Heart Study (based in Massachusetts, U.S.A.) who were linked to
      friends and family members who were also participants in the same study. Men were
      more likely to take aspirin if a male friend had recently been taking aspirin,
      and women were more likely to take aspirin if a brother had recently been taking
      aspirin. Men were also more likely to take aspirin if a brother recently had a
      cardiovascular event, and women were more likely to take aspirin if a female
      friend recently experienced a cardiovascular event. Aspirin use is correlated
      with the health and behavior of friends and family. These findings add to a
      growing body of evidence which suggests that behavioral changes that promote
      cardiovascular health may spread through social networks.

PMID- 22361090
TI  - Women's health, men's health, and gender and health: implications of
      intersectionality.
AB  - Although intersectionality is now recognized in the context of women's health,
      men's health, and gender and health, its full implications for research, policy,
      and practice have not yet been interrogated. This paper investigates, from an
      intersectionality perspective, the common struggles within each field to confront
      the complex interplay of factors that shape health inequities. Drawing on
      developments within intersectionality scholarship and various sources of research
      and policy evidence (including examples from the field of HIV/AIDS), the paper
      demonstrates the methodological feasibility of intersectionality and in
      particular, the wide-ranging benefits of de-centering gender through
      intersectional analyses.

PMID- 22361091
TI  - Is parental socio-economic status related to the initiation of substance abuse by
      young people in an English city? An event history analysis.
AB  - This paper aims to examine the relationship between parental socio-economic
      status (SES) and adolescent substance use. The central question posed in the
      title is approached in two stages. First, theoretical and empirical research in
      this area is reviewed. Second, data from an ongoing longitudinal study of young
      people in England (the Peterborough Adolescent and Young Adult Development Study-
      PADS+) are used to highlight the nature of this relationship in one city. Results
      from discrete-time event history analyses show that when examining what predicts
      initiation of substance use, familial and demographic factors emerge as important
      predictors, but SES does not appear to be relevant. The concluding discussion
      focuses on whether support is found for hypotheses derived from the existing
      literature and implications for future research.

PMID- 22361092
TI  - To have or not to have another child: life cycle, health and cost considerations
      of Ghanaian women.
AB  - Given that fertility rates are high in most sub-Saharan countries, it is
      critically important to understand the drivers of the demand for children to
      inform population reduction policies. Yet little is known about the individual
      level factors that drive the desire for fertility limitation. The desire to limit
      births may be driven by the achievement of family size targets. However, since
      children are born at different stages of the life course, fertility desires may
      also be influenced by past reproductive, socio-economic experiences, and
      perceptions about future welfare. In this study, the determinants of the desire
      to stop childbearing were analyzed at the individual-level using prospective
      longitudinal data (1998-2003) on the reproductive lives of women in six
      communities in southern Ghana. Using variation within-woman, we modeled the
      impact of changes in reproductive life cycle events, health status, perceptions
      of future household economic conditions, perceptions of the cost of additional
      children, and spousal interactions on a woman's fertility preferences. We found
      that the desire to stop childbearing is influenced by reproductive life stage
      (such as age, parity); events (marital transitions, child death); perceptions of
      personal health (particularly anticipated demands of the next pregnancy on the
      woman's health); the household's economic welfare; and the overall subjective
      cost of children. The economic utility models which emphasize cost/benefit
      considerations, as well as the anthropological and sociological theories which
      emphasize norms, appear to be validated in this empirical analysis in that both
      subjective elements and normative considerations are incorporated into fertility
      decisions.

PMID- 22361093
TI  - Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge
      instrument in Malaysia.
AB  - BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and
      its medications can be used as one of the outcome measures to assess the
      effectiveness of educational intervention. To date, no such instrument has been
      validated in Malaysia. Therefore, the aim of this study was to evaluate the
      validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL)
      knowledge instrument for assessing the knowledge of patients with type 2 diabetes
      in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains:
      diabetes, hypertension, hyperlipidemia, medications and general issues was
      designed and tested. One point was given for every correct answer, whilst zero
      was given for incorrect answers. Scores ranged from 0 to 28, which were then
      converted into percentage. This was administered to 77 patients with type 2
      diabetes in a tertiary hospital, who were on medication(s) for diabetes and who
      could understand English (patient group), and to 40 pharmacists (professional
      group). The DHL knowledge instrument was administered again to the patient group
      after one month. Excluded were patients less than 18 years old. RESULTS: Flesch
      reading ease was 60, which is satisfactory, while the mean difficulty factor(SD)
      was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy.
      Internal consistency of the instrument was good, with Cronbach's alpha = 0.791.
      The test-retest scores showed no significant difference for 26 out of the 28
      items, indicating that the questionnaire has achieved stable reliability. The
      overall mean(SD) knowledge scores was significantly different between the patient
      and professional groups [74.35(14.88) versus 93.84(6.47), p < 0.001]. This means
      that the DHL knowledge instrument could differentiate the knowledge levels of
      participants. The DHL knowledge instrument shows similar psychometric properties
      as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument
      shows good promise to be adopted as an instrument for assessing diabetic
      patients' knowledge concerning their disease conditions and medications in
      Malaysia.

PMID- 22361094
TI  - Grisel's syndrome: a rare complication of tonsillectomy.
AB  - OBJECTIVES: To discuss the pathophysiology of atlanto-axial subluxation as a rare
      complication of tonsillectomy, and to discuss the important radiological findings
      for diagnosis and treatment planning. CASE REPORT: We report a case of post
      tonsillectomy atlanto-axial subluxation, also known as Grisel's syndrome, in a
      child. On the third day after surgery, the boy presented with torticollis with no
      neurological deficit. Rotatory atlanto-axial subluxation was clearly shown in
      computed tomography scans of the neck. Cervical traction for one week
      successfully reduced the subluxation, with no long-term sequelae. CONCLUSION: Pre
      existing cervical ligamentous laxity and post-operative infection are believed to
      be the main causes of Grisel's syndrome. Although it is rare, patients are
      advised to seek treatment early if any neck pain or fever persists. Early
      diagnosis is important for better treatment outcome. Initial conservative
      measures are advised before more invasive cervical traction is adopted.

PMID- 22361095
TI  - Augmented healing of critical-size calvarial defects by baculovirus-engineered
      MSCs that persistently express growth factors.
AB  - Repair of large calvarial bony defects remains clinically challenging because
      successful spontaneous calvarial re-ossification rarely occurs. Although bone
      marrow-derived mesenchymal stem cells (BMSCs) genetically engineered with
      baculovirus (BV) for transient expression of osteogenic/angiogenic factors hold
      promise for bone engineering, we hypothesized that calvarial bone healing
      necessitates prolonged growth factor expression. Therefore, we employed a hybrid
      BV vector system whereby one BV expressed FLP while the other harbored the BMP2
      (or VEGF) cassette flanked by Frt sequences. Transduction of rabbit BMSCs with
      the FLP/Frt-based BV vector led to FLP-mediated episome formation, which not only
      extended the BMP2/VEGF expression beyond 28 days but augmented the BMSCs
      osteogenesis. After allotransplantation into rabbits, X-ray, PET/CT, MUCT and
      histological analyses demonstrated that the sustained BMP2/VEGF expression
      remarkably ameliorated the angiogenesis and regeneration of critical-size (8 mm)
      calvarial defects, when compared with the group implanted with BMSCs transiently
      expressing BMP2/VEGF. The prolonged expression by BMSCs accelerated the bone
      remodeling and regenerated the bone through the natural intramembranous pathway,
      filling ~83% of the area and ~63% of the volume in 12 weeks. These data
      implicated the potential of the hybrid BV vector to engineer BMSCs for sustained
      BMP2/VEGF expression and the repair of critical-size calvarial defects.

PMID- 22361097
TI  - Cubic sub-20 nm NaLuF(4)-based upconversion nanophosphors for high-contrast
      bioimaging in different animal species.
AB  - A new upconversion luminescence (UCL) nanophosphors based on host matrix of cubic
      NaLuF(4) with bright luminescence have been synthesized by a solvothermal method,
      facilitate the nanocrystals potential candidates for imaging in vivo, especially
      large-animals. The sub-20 nm NaLuF(4) co-doped Yb(3+) and Er(3+) (Tm(3+)) showed
      about 10-fold stronger UCL emission than that of corresponding hexagonal NaYF(4)
      based nanocrystals with a 20 nm diameter. Near-infrared to near-infrared (NIR-to
      NIR) UCL emission of PAA-coated NaLuF(4):20%Yb,1%Tm (PAA-Lu(Tm)) can penetrate
      >1.5 cm tissue of pork with high contrast. Based on super-strong UCL emission and
      deep penetration, PAA-Lu(Tm) as optical bioprobe has been demonstrated by in vivo
      UCL imaging of a normal black mouse, even rabbit with excellent signal-to-noise
      ratio. Furthermore, such cubic NaLuF(4)-based nanophosphor was applied in lymph
      node imaging of live Kunming mouse with rich white fur.

PMID- 22361096
TI  - The use of chitosan based hydrogel for enhancing the therapeutic benefits of
      adipose-derived MSCs for acute kidney injury.
AB  - Transplantation of mesenchymal stem cells (MSCs) has been reported a great
      therapeutic potential for acute kidney injury (AKI). However, the therapeutic
      benefits are limited due to the low retention and survival of transplanted cells
      within target sites. In this study, thermosensitive chitosan chloride (CSCl)
      hydrogel was explored as injectable scaffold for adipose-derived MSCs (ADMSCs)
      delivery into ischemia/reperfusion (I/R) induced acute kidney injury (AKI).
      Thermosensitive CSCl hydrogels with/without ADMSCs were injected into the I/R
      site of rat AKI models. Dihydroethidium staining was used to detect the number of
      ROS in vivo. In order to track ADMSCs in vivo, ADMSCs were transfected with
      firefly luciferase and monomeric red fluorescent protein reporter genes (fluc
      mrfp). The retention and survival of ADMSC were assessed using bioluminescence
      imaging, differentiation behaviors of ADMSCs were investigated using
      immunofluorescent and immunohistochemical staining. Proliferation and apoptosis
      of host renal cell in vivo were characterized by PCNA and TUNEL staining. Results
      suggested that CSCl hydrogels could improve the retention and survival of grafted
      ADMSCs, moreover, CSCl hydrogels could enhance the proliferation activity and
      reduce apoptosis of host renal cells. At 4 weeks, significant improvement of the
      renal function, microvessel density and tubular cell proliferation were observed
      in CSCl hydrogels with ADMSCs groups. Therefore, the application of
      thermosensitive CSCl hydrogel as scaffold for ADMSCs delivery into renal region
      could resolve the main obstacle of cell transplantation for acute kidney injury
      (AKI). Therefore, CSCl hydrogel is a potential cell carrier for treatment of AKI.

PMID- 22361098
TI  - Stability of influenza vaccine coated onto microneedles.
AB  - A microneedle patch coated with vaccine simplifies vaccination by using a patch
      based delivery method and targets vaccination to the skin for superior
      immunogenicity compared to intramuscular injection. Previous studies of
      microneedles have demonstrated effective vaccination using freshly prepared
      microneedles, but the issue of long-term vaccine stability has received only
      limited attention. Here, we studied the long-term stability of microneedles
      coated with whole inactivated influenza vaccine guided by the hypothesis that
      crystallization and phase separation of the microneedle coating matrix damages
      influenza vaccine coated onto microneedles. In vitro studies showed that the
      vaccine lost stability as measured by hemagglutination activity in proportion to
      the degree of coating matrix crystallization and phase separation. Transmission
      electron microscopy similarly showed damaged morphology of the inactivated virus
      vaccine associated with crystallization. In vivo assessment of immune response
      and protective efficacy in mice further showed reduced vaccine immunogenicity
      after influenza vaccination using microneedles with crystallized or phase
      separated coatings. This work shows that crystallization and phase separation of
      the dried coating matrix are important factors affecting long-term stability of
      influenza vaccine-coated microneedles.

PMID- 22361099
TI  - Strategies to reduce dendritic cell activation through functional biomaterial
      design.
AB  - Dendritic cells play a key role in determining adaptive immunity, and there is
      growing interest in characterizing and manipulating the interactions between
      dendritic cells and biomaterial surfaces. Contact with several common
      biomaterials can induce the maturation of immature dendritic cells, but
      substrates that reduce dendritic cell maturation are of particular interest
      within the field of cell-based therapeutics where the goal is to reduce the
      immune response to cell-laden material carriers. In this study, we use a
      materials-based strategy to functionalize poly(ethylene glycol) hydrogels with
      immobilized immunosuppressive factors (TGF-beta1 and IL-10) to reduce the
      maturation of immature dendritic cells. TGF-beta1 and IL-10 are commonly employed
      as soluble factors to program dendritic cells in vitro, and we demonstrate that
      these proteins retain bioactivity towards dendritic cells when immobilized on
      hydrogel surfaces. Following stimulation with lipopolysaccharide (LPS) and/or
      cytokines, a dendritic cell line interacting with the surfaces of
      immunosuppressive hydrogels expressed reduced markers of maturation, including IL
      12 and MHCII. The bioactivity of these immunomodulatory hydrogels was further
      confirmed with primary bone marrow-derived dendritic cells (BMDCs) isolated from
      non-obese diabetic (NOD) mice, as quantified by a decrease in activation markers
      and a significantly reduced capacity to activate T cells. Furthermore, by
      introducing a second signal to promote BMDC-material interactions combined with
      the presentation of tolerizing signals, the multifunctional PEG hydrogels were
      found to further increase signaling towards BMDCs, as evidenced by greater
      reductions in maturation markers.

PMID- 22361100
TI  - Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the
      eradication of head and neck squamous cell carcinoma-derived cancer stem cells.
AB  - Metastasis is the major cause of high mortality in head and neck squamous cell
      carcinoma (HNSCC), in which HNSCC-derived cancer stem cells (CSCs) may be
      involved. Several reports have coupled non-viral gene delivery with RNA
      interference (RNAi) to target specific genes in cancer cells. However, the
      delivery efficiency of RNAi is limited and remained to be improved. Moreover, the
      therapeutic effect of non-viral gene delivery approaches on HNSCC-derived CSCs is
      still uncertain. In this study, we found that EZH2 and Oct4 are upregulated in
      HNSCC-derived ALDH1+/CD44+ CSC-like cells. Polyurethane-short branch PEI (PU-PEI)
      based administration of double-stranded DNA (dsDNA) encoding small interfering
      RNA (siRNA) against EZH2 and Oct4 (siEZH2/siOct4) led to partial anti-cancer
      capacity and mild suppression of CSC-like properties. By pre-conjugation of
      nuclear localization signal (NLS) to siRNA-expressing dsDNA, the anti-cancer
      efficacy was enhanced due to elevated nuclear delivery. Notably, the NLS
      preconjugated siEZH2/siOct4 constructs remarkably repressed epithelial
      mesenchymal transdifferentiation (EMT) and radioresistance in ALDH1+/CD44+ CSC
      like cells, in which Wnt5A and CyclinD1 may be involved respectively. We
      furthermore demonstrated that this improved method was capable of reducing tumor
      growth and metastasis in vivo. Our findings may provide a feasible non-viral gene
      delivery method to eradicate HNSCC-derived CSCs and improve HNSCC therapy.

PMID- 22361102
TI  - Evidence for language-specific influence on the preference of stress patterns in
      infants learning an Iambic language (Hebrew).
AB  - PURPOSE: The ability of infants to develop recognition of a common stress pattern
      that is language specific has been tested mainly in trochaic languages with a
      strong-weak (SW) stress pattern. The goals of the present study were: (a) to test
      Hebrew-learning infants on their stress pattern preference in the Hebrew
      language, for which the weak-strong (WS) stress pattern is the common one, and
      (b) to test whether the infants would generalize any preference for the common
      stress pattern in Hebrew to English words, which belong to a different rhythmic
      class. METHOD: Fifty-six 9-month-old Hebrew-learning infants were tested on their
      preference for SW and WS stress patterns using Hebrew and English bisyllabic
      words with the head-turn preference procedure. RESULTS: The infants showed
      preference for WS Hebrew words but not for SW English words. CONCLUSION: Hebrew
      learning infants recognize the common stress pattern in their native language,
      supporting language-specific distributional learning by infants. This
      recognition, however, is not generalized to a foreign language with different
      prosodic characteristics.

PMID- 22361101
TI  - Bilingual children with nonsyndromic cleft lip and/or palate: language and memory
      skills.
AB  - PURPOSE: Research shows that monolingual children with cleft lip and/or palate
      (CLP) have a higher incidence of cognitive-linguistic deficits, but it is not
      clear whether bilingual preschool children with CLP are especially vulnerable
      because they need to acquire 2 languages. We tested the hypothesis that bilingual
      children with CLP score lower than bilingual children with typical development
      (TD) on receptive vocabulary, verbal memory, and visuospatial memory. METHOD:
      Participants were 86 bilingual CLP children and 100 TD children 3-6 years of age,
      dominant in English or Mandarin. Each child completed assessments of English and
      Mandarin vocabulary, verbal and visuospatial short-term and working memory,
      hearing, and articulation. RESULTS: With analysis of covariance controlling for
      age and dominant language, no group differences were found between the CLP and TD
      bilingual children, although a correlational analysis indicated discrepancies in
      the relationship between variables. CONCLUSIONS: The findings do not support the
      hypothesis that preschool children with CLP score lower than preschool children
      with TD on receptive vocabulary and memory measures. Longitudinal research
      examining literacy skill development is needed to establish whether the deficits
      reported for school-age monolingual children with CLP become more obvious in
      bilingual children in later years, especially when the medium of instruction is
      the child's nondominant language.

PMID- 22361103
TI  - Monosyllabic Mandarin tone productions by 3-year-olds growing up in Taiwan and in
      the United States: interjudge reliability and perceptual results.
AB  - PURPOSE: The author compared monosyllabic Mandarin lexical tones produced by 3
      year-old Mandarin-speaking children growing up in Taiwan and in the United
      States. METHOD: Following the procedures in Wong, Schwartz, and Jenkins (2005),
      the author collected monosyllabic tone productions from 3-year-old Mandarin
      speaking children in Taiwan and low-pass filtered them to eliminate lexical
      information but retain tone information. Five Mandarin-speaking adults residing
      in Taiwan categorized these filtered tones and those produced by the Mandarin
      speaking children growing up in the United States, the latter of which was
      reported in Wong et al. (2005). Agreements on tone categorization by judges
      residing in Taiwan and in the United States were evaluated. Tone accuracy of
      children growing up in Taiwan and the United States were examined and compared.
      RESULTS: The Mandarin-speaking judges residing in the United States and in Taiwan
      showed high agreements on tone categorization. None of the 4 tones produced by
      the Mandarin-speaking children growing up in the United States and in Taiwan was
      adultlike.Children in Taiwan made more errors in Tone 2 and Tone 4 than did 
      Mandarin-speaking children growing up in the United States. Accuracy rates of
      Tone 1 and Tone 3 were comparable in the 2 groups of children. CONCLUSION:
      Mandarin tone acquisition is a protracted process. Three-year-old Mandarin
      speaking children growing up in Taiwan and the United States show similar
      developmental patterns and have not yet produced monosyllabic tones with
      adultlike accuracy.

PMID- 22361104
TI  - A comparison of developmental social-pragmatic and naturalistic behavioral
      interventions on language use and social engagement in children with autism.
AB  - PURPOSE: Developmental social-pragmatic and naturalistic behavioral interventions
      share a number of features, but they differ in their use of facilitative
      strategies and direct elicitation of child language. In this study, the authors
      investigated whether these approaches produce different language and social
      outcomes in young children with autism. METHOD: The authors used an ABACAD design
      to compare the effects of a developmental social-pragmatic, naturalistic
      behavioral, and combined intervention on language type and function and social
      engagement in 5 children with autism. RESULTS: Milieu teaching and the combined
      intervention produced higher rates of language targets than did responsive
      interaction. An analysis of the type and function of language targets suggested
      that differences between conditions were driven primarily by prompted-and, to a
      lesser extent, spontaneous-requests. Social engagement ratings were higher during
      each intervention than at baseline, but differences between treatment conditions
      were not consistent across children. CONCLUSIONS: For children with autism,
      naturalistic interventions that use direct elicitation of child language lead to
      greater short-term gains in the use of expressive language targets-in particular,
      prompted requests-than interventions that use facilitative strategies only. All 3
      naturalistic language interventions can promote social engagement. For some
      children, the combined use of direct elicitation and responsiveness-based
      strategies may enhance treatment response.

PMID- 22361105
TI  - Influences of social and style variables on adult usage of African American
      English features.
AB  - PURPOSE: In this study, the authors examined the influences of selected social
      (gender, employment status, educational achievement level) and style variables
      (race of examiner, interview topic) on the production of African American English
      (AAE) by adults. METHOD: Participants were 50 African American men and women,
      ages 20-30 years. The authors used Rapid and Anonymous Survey (RAS) methods to
      collect responses to questions on informal situational and formal message
      oriented topics in a short interview with an unacquainted interlocutor. RESULTS:
      Results revealed strong systematic effects for academic achievement, but not
      gender or employment status. Most features were used less frequently by
      participants with higher educational levels, but sharp declines in the usage of 5
      specific features distinguished the participants differing in educational
      achievement. Strong systematic style effects were found for the 2 types of
      questions, but not race of addressee. The features that were most commonly used
      across participants-copula absence, variable subject-verb agreement, and
      appositive pronouns-were also the features that showed the greatest style
      shifting. CONCLUSIONS: The findings lay a foundation with mature speakers for
      rate-based and feature inventory methods recently shown to be informative for the
      study of child AAE and demonstrate the benefits of the RAS.

PMID- 22361106
TI  - Identifying a comparison for matching rough voice quality.
AB  - PURPOSE: Perceptual estimates of voice quality obtained using rating scales are
      subject to contextual biases that influence how individuals assign numbers to
      estimate the magnitude of vocal quality. Because rating scales are commonly used
      in clinical settings, assessments of voice quality are also subject to the
      limitations of these scales. Instead, a matching task can be used to obtain
      objective measures of voice quality, thereby facilitating model development and
      tools for clinical use. METHOD: Twenty-seven individuals participated in a rating
      task or at least 1 of 3 matching tests (named after their modulation functions:
      SINE, SQUARE, POWER) to quantify the degree of roughness in dysphonic voice
      stimuli. Participants evaluated the roughness of 34 voice samples using an
      amplitude-modulated complex carrier. RESULTS: The matching thresholds were highly
      correlated with the ratings estimates. Reliability of thresholds did not
      significantly differ across tasks, but linear regressions showed that the POWER
      test resulted in larger perceptual distances. CONCLUSIONS: A matching task can be
      used to obtain reliable estimates of roughness in dysphonic voices. The POWER
      comparison is recommended because the variability in matching thresholds across
      the range of roughness was evenly distributed, and the perceptual distances
      between stimuli were maximized.

PMID- 22361107
TI  - Complex coacervation of collagen hydrolysate extracted from leather solid wastes
      and chitosan for controlled release of lavender oil.
AB  - In the world, approximately 600,000 metric tonnes of chromium-containing solid
      wastes are generated by the leather industry each year. Environmental concerns
      and escalating landfill costs are becoming increasingly serious problems to the
      leather industry and seeking solutions to these problems is a prime concern in
      much research today. In this study, solid collagen-based protein hydrolysate was
      isolated from chromium-tanned leather wastes and its chemical properties were
      determined. Microcapsules of collagen hydrolysate (CH) - chitosan (C) crosslinked
      with glutaraldehyde (GA) containing Lavender oil (LO) were prepared by complex
      coacervation method. The effects of various processing parameters, including the
      CH to C ratio, LO content, and GA, on the oil load (%), oil content (%),
      encapsulation efficiency (%) and release rate of LO from microcapsules were
      investigated. As the ratio of C present in the CH/C mixture and crosslinking
      density increased, the release rate of LO from microcapsules slowed down. Optical
      and scanning electron microscopy images illustrated that the LO microcapsules
      were spherical in shape. Fourier transform infrared spectroscopy (FTIR) studies
      confirmed that there was no significant interaction between CH/C complex and LO.

PMID- 22361108
TI  - REDD+ readiness implications for Sri Lanka in terms of reducing deforestation.
AB  - Any system to compensate countries for reduced emissions from deforestation and
      forest degradation (REDD+) requires a historical reference level against which
      future performance can be measured. Here we examine the possibilities Sri Lanka,
      a small forest country with limited data on forest carbon stocks, has to get
      ready for REDD+. We construct a historical reference level using available forest
      inventory data combined with updated 2008 and 2009 in situ carbon density data
      for Sri Lankan forests. Furthermore, we use a combination of qualitative and
      quantitative data to attribute the clearing of Sri Lankan forests in the latest
      years for which national forest inventory data are available, 1992-1996, to
      various proximate drivers and to estimate the opportunity cost of forest
      conservation. We estimate that baseline deforestation emissions in Sri Lanka
      amounted to 17MtCO(2)yr(-1) in the 1992-1996 period, but conclude that it is
      challenging for Sri Lanka to produce a robust and accurate reference level due to
      the lack of nationally based inventories. We find that the majority of forest
      clearing (87%) is due to small-scale, rainfed farming, with the two other major
      drivers being rice and tea cultivation. Further, Sri Lankan revenues from REDD+
      participation could be substantial, but they are sensitive to REDD+ policy
      transaction cost, highly uncertain timber revenues, and particularly the carbon
      price paid for emission reductions. The latter needs to be higher than $5
      10/tCO(2) if there are to be substantial incentives for Sri Lanka to participate
      in REDD+. There is, however, a large gap in the knowledge of deforestation
      drivers that needs to be filled if Sri Lanka is to formulate an effective policy
      response to forest degradation in REDD+. For successful REDD+ implementation in
      Sri Lanka to happen, technological assistance, readiness assistance, and
      continued political momentum are crucial.

PMID- 22361109
TI  - Values, attitudes and perceptions of managers as predictors of corporate
      environmental responsiveness.
AB  - We examine whether managers' values, attitudes, and perceptions influence the
      greening of organizations. To that purpose, we specify and test a model of
      corporate environmental responsiveness (CER), drawing upon a modified version of
      the theory of planned behavior and the value-belief-norm theory. Based on survey
      data from 142 Greek companies, we find that top managers' personal values
      influence responses indirectly, through shaping their environmental attitudes,
      while direct relationship is not significant. Subjective norms, expressing
      stakeholder expectations, do affect CER, with their effect being stronger than
      that of attitudes. Managers' perceived ability to handle environmental issues
      also appears to influence responses. Results have theoretical implications,
      indicating the significant role of managers' values, attitudes and perceptions in
      a firm's environmental response. Practical implications are discussed in relation
      to selection of managers and training.

PMID- 22361110
TI  - Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle
      disease virus infection.
AB  - BACKGROUND: Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease
      (ND) viruses are the two most important poultry viruses in the world, with the
      ability to cause classic central nervous system dysfunction in poultry and
      migratory birds. To elucidate the mechanisms of neurovirulence caused by these
      viruses, a preliminary study was design to analyze host's cellular responses
      during infections of these viruses. METHODS: An improved mRNA differential
      display technique (Gene FishingTM) was undertaken to analyze differentially
      expressed transcripts regulated during HPAI H5N1 and velogenic neurotropic NDV
      infections of whole brain of chickens. The identification of differentially
      expressed genes (DEGs) was made possible as this technique uses annealing control
      primers that generate reproducible, authentic and long PCR products that are
      detectable on agarose gels. RESULTS: Twenty-three genes were identified to be
      significantly regulated during infections with both viruses, where ten of the
      genes have been selected for validation using a TaqMan(r) based real time
      quantitative PCR assay. Some of the identified genes demonstrated to be key
      factors involving the cytoskeletal system, neural signal transduction and protein
      folding during stress. Interestingly, Septin 5, one of the genes isolated from
      HPAI H5N1-infected brain tissues has been reported to participate in the
      pathogenic process of Parkinson's disease. CONCLUSIONS: In this limited study,
      the differentially expressed genes of infected brain tissues regulated by the
      viruses were found not to be identical, thus suggesting that their neurovirulence
      and neuropathogenesis may not share similar mechanisms and pathways.

PMID- 22361111
TI  - Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin
      resistance in xenograft models.
AB  - The Anterior Gradient (AGR) genes AGR2 and AGR3 are part of the Protein Disulfide
      Isomerase (PDI) family and harbour core thioredoxin folds (CxxS motifs) that have
      the potential to regulate protein folding and maturation. A number of proteomics
      and transcriptomics screens in the fields of limb regeneration, cancer cell
      metastasis, pro-oncogenic oestrogen-signalling, and p53 regulation have
      identified AGR2 as a novel component of these signalling pathways. Curiously,
      despite the fact that the AGR2 and AGR3 genes are contiguous on chromosome 7p21.1
      3, the AGR3 protein has rarely been identified in such OMICs screens along with
      AGR2 protein. Therefore there is little information on how AGR3 protein is
      expressed in normal and diseased states. A panel of three monoclonal antibodies
      was generated towards AGR3 protein for identifying novel clinical models that can
      be used to define whether AGR3 protein could play a positive or negative role in
      human cancer development. One monoclonal antibody was AGR3-specific and bound a
      linear epitope that could be defined using both pep-scan and phage-peptide
      library screening. Using this monoclonal antibody, endogenous AGR3 protein
      expression was shown to be cytosolic in four human ovarian cancer subtypes;
      serous, endometrioid, clear cell, and mucinous. Mucinous ovarian cancers produced
      the highest number of AGR3 positive cells. AGR3 expression is coupled to AGR2
      expression only in mucinous ovarian cancers, whereas AGR3 and AGR2 expressions
      are uncoupled in the other three types of ovarian cancer. AGR3 expression in
      ovarian cancer is independent of oestrogen-receptor expression, which is distinct
      from the oestrogen-receptor dependent expression of AGR3 in breast cancers.
      Isogenic cancer cell models were created that over-express AGR3 and these
      demonstrated that AGR3 mediates cisplatin-resistance in mouse xenografts. These
      data indicate that AGR3 is over-expressed by a hormone (oestrogen-receptor alpha)
      independent mechanism and identify a novel protein-folding associated pathway
      that could mediate resistance to DNA-damaging agents in human cancers.

PMID- 22361112
TI  - First report on interferon related developmental regulator-1 from Macrobrachium
      rosenbergii: bioinformatic analysis and gene expression.
AB  - This study reports the first full length gene of interferon related developmental
      regulator-1 (designated as MrIRDR-1), identified from the transcriptome of
      Macrobrachium rosenbergii. The complete gene sequence of the MrIRDR-1 is 2459
      base pair long with an open reading frame of 1308 base pairs and encoding a
      predicted protein of 436 amino acids with a calculated molecular mass of 48 kDa.
      The MrIRDR-1 protein contains a long interferon related developmental regulator
      super family domain between 30 and 330. The mRNA expressions of MrIRDR-1 in
      healthy and the infectious hypodermal and hematopoietic necrosis virus (IHHNV)
      infected M. rosenbergii were examined using qRT-PCR. The MrIRDR-1 is highly
      expressed in hepatopancreas along with all other tissues (walking leg, gills,
      muscle, haemocyte, pleopods, brain, stomach, intestine and eye stalk). After
      IHHNV infection, the expression is highly upregulated in hepatopancreas. This
      result indicates an important role of MrIRDR-1 in prawn defense system.

PMID- 22361114
TI  - Getting real about semantic illusions: rethinking the functional role of the P600
      in language comprehension.
AB  - In traditional theories of language comprehension, syntactic and semantic
      processing are inextricably linked. This assumption has been challenged by the
      'semantic illusion effect' found in studies using event related brain potentials.
      Semantically anomalous sentences did not produce the expected increase in N400
      amplitude but rather one in P600 amplitude. To explain these findings, complex
      models have been devised in which an independent semantic processing stream can
      arrive at a sentence interpretation that may differ from the interpretation
      prescribed by the syntactic structure of the sentence. We review five such multi
      stream models and argue that they do not account for the full range of relevant
      results because they assume that the amplitude of the N400 indexes some form of
      semantic integration. Based on recent evidence we argue that N400 amplitude might
      reflect the retrieval of lexical information from memory. On this view, the
      absence of an N400-effect in semantic illusion sentences can be explained in
      terms of priming. Furthermore, we suggest that semantic integration, which has
      previously been linked to the N400 component, might be reflected in the P600
      instead. When combined, these functional interpretations result in a single
      stream account of language processing that can explain all of the Semantic
      Illusion data.

PMID- 22361113
TI  - An unexpected loss of domains in the conservative evolution ninth complement
      component in a higher teleost, Miichthys miiuy.
AB  - The complement systems of fish are well developed and play an important role in
      the innate immune response. C9 is the ninth member of complement components,
      involved in creating the membrane attack complex (MAC). In the present study, a
      truncated C9 cDNA sequence encoding 461 amino acids was cloned and characterized
      in the miiuy croaker (Miichthys miiuy). Typical fish C9 molecules have five
      characteristic modular domains, i.e. TSP1, LDLRA, MACPF, EGF, and a second TSP
      domain which is absent in mammalian counterparts. While in miiuy croaker, this
      truncated C9 presents only TSP1, LDLRA and MACPF domains. It is the first time of
      finding a truncated C9 in teleost components. RT-PCR analysis detected these C9
      transcripts among all tissues examined, demonstrating its constitutive expression
      pattern in healthy fish. The highest levels of transcripts were detected in liver
      of both healthy and pathogen-infected miiuy croaker. Its constitutive and
      inducible expression pattern of this truncated C9 in liver is similar to most
      complement components which belong to the type of acute-phase proteins and are in
      general of hepatic origin. We cannot exclude the possibility that miiuy croaker
      presents the typical C9 although it has not yet been found. The molecular
      evolutionary analysis showed that this truncated C9 of miiuy croaker had a
      significantly higher omega value comparing with other fish and the positive
      selection pressure had happened on it after its divergence with other fish.

PMID- 22361115
TI  - What is the specificity of the response to the own first-name when presented as a
      novel in a passive oddball paradigm? An ERP study.
AB  - One's own first-name is a special stimulus: one's attention is more likely
      captured by hearing one's own first-name than by hearing another first-name.
      Previous event-related potential (ERP) studies demonstrated that this special
      stimulus produces differential responses both in active and in passive condition.
      Such results suggest that passively hearing one's own first-name triggers
      processing levels generally activated by the explicit detection of stimuli. This
      questions about the particular power of the own first-name to automatically
      orient attention, but no study investigated the specific response to this special
      stimulus in a paradigm designed to study automatic attention orienting. In this
      ERP study, we compared the responses elicited by the own first-name (OWN) and one
      unfamiliar first-name (OTHER) presented, rarely, randomly and at the same
      frequency among repetitive tones (i.e., as novel stimuli in an oddball paradigm)
      while subjects (N=36) were watching a silent movie with subtitles. We tested at
      what latency the responses to OWN and OTHER diverge, and whether OWN modulates
      the brain orienting response (novelty P3). Data analysis showed specific
      responses to OWN after 300 ms. OWN only evoked a central negativity (320 ms) and
      a parietal positivity (550 ms). However, OWN had no significant effect on the
      brain orienting response (260 ms). Our results confirm that the own first-name
      does elicit a late specific brain response. However, they challenge the idea that
      in passive condition, the own first-name is systematically more powerful than
      another first-name to orient attention when it is heard unexpectedly.

PMID- 22361116
TI  - Partial reduction in neural cell adhesion molecule (NCAM) in heterozygous mice
      induces depression-related behaviour without cognitive impairment.
AB  - The neural cell adhesion molecule (NCAM) plays an important role in brain
      plasticity. Using mice deficient in all isoforms of NCAM we have previously
      demonstrated that constitutive deficiency in the NCAM gene (NCAM-/-) resulted in
      cognitive impairment, anhedonic behaviour and a reduced ability to cope with
      stress. This was accompanied by reduced basal phosphorylation of the fibroblast
      growth factor receptor 1 (FGFR1) and reduced phosphorylation of calcium
      calmodulin kinase (CaMK) II and IV and cAMP response element binding protein
      (CREB). The present study was aimed to investigate how partial deficiency in NCAM
      in mice (NCAM+/-) affected phenotype. We found that NCAM+/- mice showed a longer
      period of immobility in the tail suspension test, increased latency to feed in
      the novelty-suppressed feeding test and reduced preference for sucrose in sucrose
      preference test. Both NCAM+/- and NCAM-/- mice showed reduced extinction of
      contextual fear. In contrast to NCAM-/- mice, NCAM+/- mice did not demonstrate
      memory impairment in either object recognition or contextual fear conditioning
      tests. Levels of phosphorylated FGFR1 in the hippocampus and prefrontal/frontal
      cortex of NCAM+/- mice were partially reduced and no changes in the
      phosphorylation of CaMKII, CaMKIV or CREB in the hippocampus were found. We
      conclude that a constitutive partial reduction in NCAM proteins results in a
      behavioural phenotype related to depression without impairment in cognitive
      functions, also affecting the level of FGFR1 phosphorylation without major
      alterations in CaMKII and CaMKIV intracellular signalling. Partial reduction in
      FGFR1 phosphorylation might explain the observed behavioural phenotype in NCAM+/-
      mice.

PMID- 22361118
TI  - Recurrence of cutaneous squamous cell carcinoma at remote limb donor site.
AB  - Squamous cell skin cancer (SCC) is the second most common skin malignancy. The
      risk of metastasis is usually low and generally occurs through lymphatic spread.
      Surgical excision is the gold standard for treatment and subsequent
      reconstruction often involves a skin graft from a distant donor site. Our case
      highlights an incident in which metastatic spread of an SCC occurred in a distant
      skin graft donor site on the limb following free flap harvest.

PMID- 22361117
TI  - Accumulation of nanocarriers in the ovary: a neglected toxicity risk?
AB  - Several nanocarrier systems are frequently used in modern pharmaceutical
      therapies. Within this study a potential toxicity risk of all nanoscaled drug
      delivery systems was found. An accumulation of several structurally different
      nanocarriers but not of soluble polymers was detected in rodent ovaries after
      intravenous (i.v.) administration. Studies in different mouse species and Wistar
      rats were conducted and a high local accumulation of nanoparticles, nanocapsules
      and nanoemulsions in specific locations of the ovaries was found in all animals.
      We characterised the enrichment by in vivo and ex vivo multispectral fluorescence
      imaging and confocal laser scanning microscopy. The findings of this study
      emphasise the role of early and comprehensive in vivo studies in pharmaceutical
      research. Nanocarrier accumulation in the ovaries may also comprise an important
      toxicity issue in humans but the results might as well open a new field of
      targeted ovarian therapies.

PMID- 22361119
TI  - Ocular surface area changes after double eyelidplasty.
AB  - INTRODUCTION: Double eyelidplasty is one of the most common cosmetic surgeries in
      Asia. Subjective enlargement of the ocular surface area (OSA) after double
      eyelidplasty was appreciated by patients. Objective measurement of the OSA
      provides a more scientific result. We introduce a relatively precise method,
      using iris as a scale combined with the digital photography and software
      calculation, to measure the OSA before and after double eyelidplasty. MATERIALS
      AND METHODS: One hundred and nineteen patients (108 females and 11 males) were
      enrolled in this study. Ninety-two patients received minimally invasive double
      eyelidplasty without other procedures and 27 patients received medial
      epicanthoplasty with modified Z-plasty besides double eyelidplasty. Digital
      photographs of the operative eyes in all patients were obtained preoperatively
      and postoperatively. The image processing software we used was ImageJ (v1.43,
      National Institutes of Health, United States). Preoperative and postoperative
      OSAs were measured. The percentage of difference of the OSA between two eyes in
      same patient before and after the operation was calculated and compared. RESULTS:
      The average increase of the OSA among 238 operative eyes was 12.5 +/- 8.2%.
      Preoperative and postoperative OSA differences between two eyes in same patients
      were significantly decreased after surgery. CONCLUSION: Digital photography using
      iris as a scale combined with software calculation is an easy and convenient
      method to measure the OSA; it provides quantitative information for both
      preoperative and postoperative evaluation. Our study revealed that double
      eyelidplasty not only increased OSA but also improved ocular asymmetry after
      surgery.

PMID- 22361120
TI  - Molecular investigations into vaginal immunization with HIV gp41 antigenic
      construct H4A in a quick release solid dosage form.
AB  - A robust vaginal immune response is considered essential for an effective
      prophylactic vaccine that prevents transmission of HIV and other sexually
      acquired diseases. Considerable attention has recently focused on the potential
      of vaginally administered vaccines as a means to induce such local immunity.
      However, the potential for vaccination at this site remains in doubt as the
      vaginal mucosa is generally considered to have low immune inductive potential. In
      the current study, we explored for the first time the use of a quick release,
      freeze-dried, solid dosage system for practical vaginal administration of a
      protein antigen. These solid dosage forms overcome the common problem associated
      with leakage and poor retention of vaginally administered antigen solutions. Mice
      were immunized vaginally with H4A, an HIV gp41 envelope based recombinant
      protein, using quick release, freeze-dried solid rods, and the immune responses
      compared to a control group immunized via subcutaneous H4A injection. Vaginally
      immunized mice failed to elicit robust immune responses. Our detailed
      investigations, involving cytokine analysis, the stability of H4A in mouse
      cervicovaginal lavage, and elucidation of the state of H4A protein in the
      immediate-release dosage form, revealed that antigen instability in vaginal
      fluid, the state of the antigen in the dosage form, and the cytokine profile
      induced are all likely to have contributed to the observed lack of
      immunogenicity. These are important factors affecting vaginal immunization and
      provide a rational basis for explaining the typically poor and variable
      elicitation of immunity at this site, despite the presence of immune responsive
      cells within the vaginal mucosae. In future mucosal vaccine studies, a more
      explicit focus on antigen stability in the dosage form and the immune potential
      of available antigen-responsive cells is recommended.

PMID- 22361122
TI  - Radical surgical repair with stepwise Cabrol shunt for severe prosthetic valve
      endocarditis.
AB  - Prosthetic valve endocarditis involving other valves and cardiac structures
      requires complex surgical reconstruction, which is sometimes accompanied by
      uncontrollable bleeding. We report the case of a 41-year old man who developed
      prosthetic aortic valve endocarditis with paravalvular abscess affecting the
      intervalvular fibrous body, the mitral valve and other cardiac structures. Aortic
      root and mitral valve replacement with reconstruction of the intervalvular
      fibrous body led to torrential bleeding from the proximal aortic root
      anastomosis, which was successfully controlled by a stepwise Cabrol shunt.

PMID- 22361121
TI  - Gaviscon(r) vs. omeprazole in symptomatic treatment of moderate gastroesophageal
      reflux. a direct comparative randomised trial.
AB  - BACKGROUND: Medical management of GERD mainly uses proton pump inhibitors.
      Alginates also have proven efficacy. The aim of this trial was to compare short
      term efficacy of an alginate (Gaviscon(r), 4 * 10 mL/day) and omeprazole (20
      mg/day) on GERD symptoms in general practice. METHODS: A 14-day multicentre
      randomised double-blind double-dummy non-inferiority trial compared Gaviscon(r)
      (4 * 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn
      episodes weekly without alarm signals. The primary outcome was the mean time to
      onset of the first 24-h heartburn-free period after initial dosing. Secondary
      outcomes were the proportion of patients without heartburn by D7, pain relief by
      D7, and reduction in pain intensity by D7 and D14. RESULTS: 278 patients were
      recruited; 120 were included in the Gaviscon(r) group and 121 in the omeprazole
      group for the per protocol non-inferiority analysis. The mean time to onset of
      the first 24-h heartburn-free period after initial dosing was 2.0 (+/- 2.2) days
      for Gaviscon(r) and 2.0 (+/- 2.3) days for omeprazole (p = 0.93); mean intergroup
      difference was 0.01 +/- 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the
      lower limit of the 95% CI of -0.5 days predetermined to demonstrate non
      inferiority. The mean number of heartburn-free days by D7 was significantly
      greater in the omeprazole group: 3.7 +/- 2.3 days vs. 3.1 +/- 2.1 (p = 0.02). On
      D7, overall quality of pain relief was slightly in favour of omeprazole (p =
      0.049). There was no significant difference in the reduction in pain intensity
      between groups by D7 (p = 0.11) or D14 (p = 0.08). Tolerance and safety were good
      and comparable in both groups. CONCLUSION: Gaviscon(r) was non-inferior to
      omeprazole in achieving a 24-h heartburn-free period in moderate episodic
      heartburn, and is a relevant effective alternative treatment in moderate GERD in
      primary care. TRIAL REGISTRATION: ISRCTN62203233.

PMID- 22361123
TI  - Single-centre experience of 101 paediatric and adult Ross procedures: mid-term
      results.
AB  - We aimed to determine outcomes for the Ross procedure in paediatric and adult
      patients, with particular emphasis on survival, complication and reintervention
      rates. A retrospective review of 101 patients who had the Ross procedure in a
      congenital cardiac surgical centre serving a population of approximately 2.5
      million was performed. There were 69 adults and 32 children with a mean age of
      24.8 +/- 13.9 years. Indications for surgery were aortic stenosis (48),
      regurgitation (10), mixed disease (35) and complex left outflow tract obstruction
      (8). The mean follow-up duration was 4.7 +/- 3.7 years. The mini-inclusion
      technique was used to incorporate the autograft, and in all cases, pulmonary
      homografts were placed in the right ventricular outflow tract. Sub-aortic
      resection was also performed in six and Ross-Konno operations in eight patients.
      There were no early deaths and there was one late death secondary to
      endocarditis. Freedom from reintervention was 92% at 5 years and 77% at 10 years.
      Children were significantly more likely to require reintervention (16%, 5 of 32
      versus 4%, 3 of 69, P = 0.05). The Ross procedure carries low early and mid-term
      mortality, and reintervention rates appear acceptable. The Ross procedure should
      be considered a feasible alternative to prosthetic valves in patients who require
      aortic valve replacement.

PMID- 22361124
TI  - Human mesenchymal stromal cells improve scar thickness without enhancing cardiac
      function in a chronic ischaemic heart failure model.
AB  - Few data address the role of human mesenchymal stromal cells (MSCs) in the
      management of chronic ischaemic heart failure. We assessed their effect in immune
      deficient animals. MSCs were cultured from bone marrow of human volunteers. Non
      obese diabetes severe combined immunodeficiency (NOD/SCID) gamma null mice were
      randomly assigned to intramyocardial injection of human MSCs or phosphate
      buffered saline 4 weeks after induction of acute myocardial infarction (MI).
      Echocardiography was performed 4 weeks after MI and 1 and 4 weeks after
      injection. Donor cell chimerism was assessed by DNA for human Alu sequences 2 and
      4 weeks after injection. Histological assessment and quantification of
      neovascularization were determined 4 weeks after treatment. Donor MSCs at
      frequencies of 0.006 and 0.001% were present 2 and 4 weeks after cell injection,
      respectively. The infarcted ventricular wall was significantly thicker in the
      cohort receiving MSCs compared with control mice. There was no difference in
      fractional shortening, left ventricular dimensions or scar area between the
      groups. Small vessel density was also similar between the groups. Human MSCs
      increased the thickness of the infarcted ventricular wall without improving
      cardiac function in this chronic ischaemic heart failure model. Further studies
      are required to assess the benefit of MSCs in this setting.

PMID- 22361125
TI  - Resection of bronchial stricture and destroyed lung after pulmonary tuberculosis.
AB  - We present a 53-year old man with destroyed lung syndrome (right upper and middle
      lobes and S6 of lower lobe with bronchial stricture between the right main and
      intermediate bronchus) due to tuberculosis 25 years earlier. Aspergillus
      infection in the destroyed lung was suspected on the basis of antigen positivity.
      The patient underwent right upper and middle lobectomy, S6 segmentectomy and
      bronchial resection from the distal end of the right main bronchus to the
      proximal end of the right basal bronchus. The membranous part of the right main
      bronchus was cerclaged in order to circularize the flattened bronchus and to
      match its diameter with that of the basal bronchus. End-to-end anastomosis was
      then carried out. The postoperative course was uneventful. Pathological
      examination revealed Aspergillus infection in the cavity of the destroyed lung.
      Bronchoscopic findings 6 weeks after surgery revealed good healing of the
      anastomosed portion without stenosis.

PMID- 22361126
TI  - Surgical treatment for retrograde type A aortic dissection after endovascular
      stent graft placement for type B dissection.
AB  - Retrograde type A aortic dissection (RTAD) is a life-threatening and
      underestimated complication of endovascular stent graft placement for type B
      dissection. Here, we retrospectively investigated our experience of surgical
      treatment for RTAD after endovascular stent graft placement for type B
      dissection. Between June 2006 and September 2011, nine patients with RTAD were
      transferred to our department for surgery. Total arch replacement was performed
      in six patients and three patients underwent subtotal arch replacement.
      Associated procedures consisted of ascending aorta replacement in nine patients,
      coronary artery bypass grafting in one patient and aortic valve plasty in two
      patients. All operations were performed under deep hypothermic circulatory arrest
      and selective antegrade cerebral perfusion. Cardiopulmonary bypass time was
      158.33 +/- 29.18 min. The myocardial ischaemic time was 78.11 +/- 28.30 min. The
      antegrade cerebral perfusion time was 38.67 +/- 12.34 min. The mean ventilation
      time was 45.63 +/- 24.74 h. A tracheotomy was necessary in one patient. The ICU
      time was 7.00 +/- 6.80 days and the in-hospital duration was 25.33 +/- 11.95
      days. There was no in-hospital mortality. The mean follow-up was 34.79 +/- 19.37
      months and eight patients are still alive. One patient was lost to follow-up.
      Surgical treatment for RTAD is a safe alternative and the results are
      encouraging.

PMID- 22361127
TI  - Treatment of congenital tracheal stenosis by balloon-expandable metallic stents
      in paediatric intensive care unit.
AB  - The aim of this study was to evaluate the use of balloon-expandable metallic
      stents in the treatment of children with congenital tracheal stenosis in whom
      conventional therapy has failed. From 2010 to 2011, balloon-expandable metallic
      stents were implanted into the trachea of eight infants aged 2-20 months in the
      paediatric intensive care unit. The infants had severe airway obstruction caused
      by congenital tracheal stenosis. Tracheal stents were placed after intraluminal
      balloon dilatation of the tracheal stenosis, inserted with balloon catheters and
      implanted into the desired position bronchoscopically. The stents were 12 to 29
      mm long and 4 mm in diameter. Seven children were relieved of airway obstruction
      after this procedure. However, a child died due to severe sepsis after the
      placement of bronchial stents. No granulation tissue developed over the stents in
      any of the children. Stents have been in place for 1-6 months after insertion
      without any other complication. Balloon-expandable metallic stents are effective
      in relieving airway obstruction by congenital tracheal stenosis in children. This
      technique may provide an important remedy for congenital tracheal stenosis in
      children.

PMID- 22361128
TI  - Accuracy of two scoring systems for risk stratification in thoracic surgery.
AB  - We investigate the suitability of the two existing risk stratification systems
      available for predicting mortality in a cohort of patients undergoing lung
      resection under a single surgeon. Data from the 290 consecutive patients who
      underwent pulmonary resection between January 2008 and January 2011 were
      extracted from a prospective clinical data base. In-hospital mortality risk
      scores are calculated for every patient by using Thoracoscore and ESOS.01 and
      were compared with actual in-hospital mortality. The receiver operating
      characteristic (ROC) curve was used to establish how well the systems rank for
      predicting patient mortality. Actual in-hospital mortality was 3.1% (n = 9).
      Thoracoscore and ESOS values (mean +/- SEM) were 4.93 +/- 0.32 and 4.08 +/- 0.41,
      respectively. The area under the ROC curve values for ESOS and Thoracoscore were
      0.8 and 0.6, respectively. ESOS was reasonably accurate at predicting the overall
      mortality (sensitivity 88% and specificity 67%), whereas Thoracoscore was a
      weaker predictor of mortality (sensitivity 67% and specificity 53%). The ESOS
      score had better predictive values in our patient population and might be easier
      to calculate. Because of their low specificity, the use of these scores should be
      limited to the assessment of outcomes of surgical cohorts, but they are not
      designed to predict risks for individual patients.

PMID- 22361129
TI  - Pulmonary lymphomatoid granulomatosis mimicking lung cancer.
AB  - Lymphomatoid granulomatosis (LYG) of the lung is an extremely rare, Epstein-Barr
      virus-related lymphoproliferative disease. We report a case of pulmonary LYG that
      presented as a large necrotic mass.

PMID- 22361130
TI  - Changes in phospholipid composition, protein content and chemical properties of
      flaxseed oil during development.
AB  - The aim of the present research is to investigate the effect of harvest date on
      the composition of flaxseed. Samples were collected at regular intervals from 7
      to 56 days after flowering (DAF) and analyzed for phospholipid composition,
      storage protein content and chemical properties. Phospholipid (PL) percentage of
      the total lipid decreased from 32.72% on the 7th DAF to 2.55% on the 56th DAF.
      The most phospholipids present in flaxseed were phosphatidylinositol (PI),
      phosphatidylethanolamine (PE) and lysophosphatidylcholine (LPC) which were highly
      unsaturated and rich in linolenic and linoleic acids, comprising together 60% of
      the total fatty acids. Chemical investigation of flaxseed oil showed overall a
      decrease in UV absorbance (K(232) and K(270)), acid value, free fatty acid
      content and an increase in peroxide value and storage protein content with
      development. At full maturity, flaxseed contained 29% proteins on a dry weight
      basis (DW %).

PMID- 22361131
TI  - N-demethylation of cyamemazine via non-classical Polonovski reaction and its
      conjugation to bovine serum albumin.
AB  - A modified Polonovski reaction has been employed to obtain the N-demethylated
      metabolite of the neuroleptic drug cyamemazine. The synthesis involves N-oxide
      formation, isolation of the corresponding N-oxide, and a FeSO(4).7H(2)O mediated
      Polonovski reaction to afford the desired monodesmethyl cyamemazine. In a
      subsequent step the hapten N-demethylcyamemazine-hemiglutarate was synthesized
      and its conjugated to bovine serum albumin (BSA).

PMID- 22361132
TI  - Tigliane diterpene esters with IFN gamma-inducing activity from the leaves of
      Aleurites fordii.
AB  - Bioactivity-guided fractionation on the leaves of Aleurites fordii led to the
      isolation of a new tigliane diterpene ester, 12-O-hexadecanoyl-7-oxo-5-ene-16
      hydroxyphorbol-13-acetate (1) along with four known compounds, 12-O-hexadecanoyl
      7-oxo-5-ene-phorbol-13-acetate (2), 12-O-hexadecanoyl-phorbol-13-acetate (3), 12
      O-hexadecanoyl-16-hydroxyphorbol-13-acetate (4), and 12-O-hexadecanoyl-4-deoxy
      4alpha-16-hydroxyphorbol-13-acetate (5). The structures of these compounds were
      determined by interpretation of NMR (1D and 2D) spectroscopic data and MS data.
      All the isolates were evaluated for their effects on the induction of IFN-gamma
      in NK92 cells. Compounds 3 and 4 exhibited the most potent responses in IFN-gamma
      induction, comparable to the positive control, phorbol 12-myristate 13-acetate
      (PMA).

PMID- 22361133
TI  - Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)
      ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase
      inhibitors.
AB  - A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones,
      has been rationally designed based on the docking model of the more potent R
      enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology
      model. Synthesis and SAR of this novel chemotype are described. Several compounds
      in the series demonstrated potent growth inhibition in a PTEN-deficient breast
      cancer cell line MDA-MB-468 under anchorage independent conditions.

PMID- 22361134
TI  - N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors:
      synthesis and biological evaluation.
AB  - A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1
      (R'=H, CH(2)Ph, COPh) substituent in conjunction with a C-3 -C=HN-C(6)H(4)-4-X
      (X=F, Me, CF(3), Cl) substituent were synthesized and evaluated as inhibitors of
      cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases,
      compounds 15 (R(1)=CH(2)Ph, X=F), 17 (R(1)=CH(2)Ph, X=CF(3)), 18 (R(1)=COPh, X=F)
      and 20 (R(1)=COPh, X=CF(3)) were identified as effective and selective COX-2
      inhibitors (COX-2 IC(50)'s=0.32-0.84 MUM range; COX-2 selectivity index (SI)=113
      to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20)
      emerged as the most potent (COX-1 IC(50) >100 MUM; COX-2 IC(50)=0.32 MUM) and
      selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX
      2 inhibitor in contrast to the reference drug indomethacin that is a potent and
      selective COX-1 inhibitor (COX-1 IC(50)=0.13 MUM; COX-2 IC(50)=6.9 MUM, COX-2
      SI=0.02). Molecular modeling studies employing compound 20 showed that the phenyl
      CF(3) substituent attached to the CN spacer is positioned near the secondary
      pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded
      (N...NH=2.85 A) to the H90 residue, and the indole N-1 benzoyl is positioned in a
      hydrophobic pocket of the COX-2 active site near W387.

PMID- 22361135
TI  - Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5
      antagonists.
AB  - A novel series of indolyl and dihydroindolyl glycinamides were identified as
      potent NPY5 antagonists with in vivo activity from screen hit 1. The
      dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced
      feeding at a dose of 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5
      agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c
      represent potential tools for further investigation into the biology of the NPY5
      receptor.

PMID- 22361136
TI  - Ketoolivosyl-tetracenomycin C: a new ketosugar bearing tetracenomycin reveals new
      insight into the substrate flexibility of glycosyltransferase ElmGT.
AB  - A new tetracenomycin analog, 8-demethyl-8-(4'-keto)-alpha-L-olivosyl
      tetracenomycin C, was generated through combinatorial biosynthesis. Streptomyces
      lividans TK 24 (cos16F4) was used as a host for expression of a 'sugar plasmid'
      (pKOL) directing the biosynthesis of NDP-4-keto-L-olivose. This strain harbors
      all of the genes necessary for production of 8-demethyl-tetracenomycin C and the
      sugar flexible glycosyltransferase ElmGT. To the best of our knowledge, this
      report represents the first characterization of a tetracenomycin derivative
      decorated with a ketosugar moiety. Also, as far as we know, 4-keto-L-olivose has
      only been described as an intermediate of oleandomycin biosynthesis, but has not
      been described before as an appendage for a polyketide compound. Furthermore,
      this report gives further insight into the substrate flexibility of ElmGT to
      include an NDP-ketosugar, which is unusual and is rarely observed among
      glycosyltransferases from antibiotic biosynthetic pathways.

PMID- 22361137
TI  - Synthesis and in vitro antitumor activity of asperphenamate derivatives as
      autophagy inducer.
AB  - In an effort to improve the aqueous solubility and the antitumor activity of
      natural product asperphenamate, we have designed and synthesized three series of
      asperphenamate derivatives, including series I (simplifying molecular skeleton
      series), series II (introducing a hydroxyl group to A-phenyl ring series) and
      series III (disrupting molecular planarity series). All derivatives have
      displayed a significantly increased solubility compared with asperphenamate.
      Their growth inhibitory activities in vitro were screened by the standard MTT
      method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the
      derivatives in series I, most of derivatives in series II and series III showed
      growth inhibitory activity. Among all derivatives, IM23b in series III showed the
      greatest potency in human breast cancer MCF-7 cells. The cellular potency of
      IM23b was approximately 1.5-fold more potent than that of cisplatin. The
      mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was
      further investigated. We concluded that the cell death was induced by autophagy
      instead of apoptosis or cell cycle arrest.

PMID- 22361138
TI  - Cerebrospinal fluid rhinorrhoea after nasal packing for epistaxis: case report.
AB  - OBJECTIVE: We report a case of traumatic cerebrospinal fluid rhinorrhoea
      following nasal packing with a Rapid Rhino inflatable balloon pack, as treatment
      for epistaxis. METHOD: Case report and review of the literature regarding this
      complication. RESULTS: A thorough literature search was performed using PubMed.
      To our best knowledge, there have been no previous reports of cerebrospinal fluid
      rhinorrhoea following nasal packing. In our case, cerebrospinal fluid leakage
      occurred due to fracture of the middle turbinate at its superior skull base
      insertion. The cerebrospinal fluid leak resolved spontaneously without the need
      for surgical intervention. CONCLUSION: This case report highlights not only the
      need for an appreciation of sinonasal anatomy and the potential risks associated
      with nasal packing, but also the need for adequate training in the use of
      commercially available nasal packs by medical practitioners attending patients
      with epistaxis.

PMID- 22361139
TI  - Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+
      exchanger-mediated mitochondrial calcium overload.
AB  - BACKGROUND: Uric acid (UA) has proven to be a causal agent in endothelial
      dysfunction in which ROS production plays an important role. Calcium overload in
      mitochondria can promote the mitochondrial production of ROS. We hypothesize that
      calcium transduction in mitochondria contributes to UA-induced endothelial
      dysfunction. METHODS AND RESULTS: We first demonstrated that high concentrations
      of UA cause endothelial dysfunction, marked by a reduction in eNOS protein
      expression and NO release in vitro. We further found that a high concentration of
      UA increased levels of [Ca2+]mito, total intracellular ROS, H2O2, and
      mitochondrial O2.-, and Deltapsimito but not the [Ca2+]cyt level. When the
      mitochondrial calcium channels NCXmito and MCU were blocked by CGP-37157 and
      Ru360, respectively, the UA-induced increases in the levels of [Ca2+]mito and
      total intracellular ROS were significantly reduced. Mitochondrial levels of O2.-
      and Deltapsimito were reduced by inhibition of NCXmito but not of MCU. Moreover,
      inhibition of NCXmito, but not of MCU, blocked the UA-induced reductions in eNOS
      protein expression and NO release. CONCLUSIONS: The increased generation of
      mitochondrial O2.- induced by a high concentration of UA is triggered by
      mitochondrial calcium overload and ultimately leads to endothelial dysfunction.
      In this process, the activation of NCXmito is the major cause of the influx of
      calcium into mitochondria. Our results provide a new pathophysiological mechanism
      for UA-induced endothelial dysfunction and may offer a new therapeutic target for
      clinicians.

PMID- 22361140
TI  - Glucose increases extracellular [Ca2+] in rat insulinoma (INS-1E) pseudoislets as
      measured with Ca2+-sensitive microelectrodes.
AB  - Secretory granules of pancreatic beta-cells contain high concentrations of Ca2+
      ions that are co-released with insulin in the extracellular milieu upon
      activation of exocytosis. As a consequence, an increase in the extracellular Ca2+
      concentration ([Ca2+]ext) in the microenvironment immediately surrounding beta
      cells should be expected following the exocytotic event. Using Ca2+-selective
      microelectrodes we show here that both high glucose and non-nutrient
      insulinotropic agents elicit a reversible increase of [Ca2+]ext within rat
      insulinoma (INS-1E) beta-cells pseudoislets. The glucose-induced increases in
      [Ca2+]ext are blocked by pretreatment with different Ca2+ channel blockers.
      Physiological agonists acting as positive or negative modulators of the insulin
      secretion and drugs known to intersect the secretory machinery at different
      levels also induce [Ca2+]ext changes as predicted on the basis of their described
      action on insulin secretion. Finally, the glucose-induced [Ca2+]ext increase is
      strongly inhibited after disruption of the actin web, indicating that the dynamic
      [Ca2+]ext changes recorded in INS-1E pseudoislets by Ca2+-selective
      microelectrodes occur mainly as a consequence of exocytosis of Ca2+-rich
      granules. In conclusion, our data directly demonstrate that the extracellular
      spaces surrounding beta-cells constitute a restricted domain where Ca2+ is co
      released during insulin exocytosis, creating the basis for an autocrine/paracrine
      cell-to-cell communication system via extracellular Ca2+ sensors.

PMID- 22361141
TI  - The neuroethics of non-invasive brain stimulation.
AB  - Transcranial direct current stimulation (TDCS) is a brain stimulation tool that
      is portable, painless, inexpensive, apparently safe, and with potential long-term
      efficacy. Recent results obtained from TDCS experiments offer exciting
      possibilities for the enhancement and treatment of normal or impaired abilities,
      respectively. We discuss new neuroethical problems that have emerged from the
      usage of TDCS, and also focus on one of the most likely future applications of
      TDCS: enhancing learning and cognition in children with typical and atypical
      development.

PMID- 22361142
TI  - Murmurations.

PMID- 22361143
TI  - Caveolae.

PMID- 22361144
TI  - The ESCRT machinery.

PMID- 22361145
TI  - High-resolution polarisation vision in a cuttlefish.

PMID- 22361146
TI  - Structure of orbitofrontal cortex predicts social influence.

PMID- 22361147
TI  - Collective migration: spatial tension relief.
AB  - Collective epithelial cell migration facilitates formation and maintenance of
      continuous sheets that line the surfaces and cavities of glands and tissues. By
      screening Rho GTPase regulators, myosin-IXA RhoGAP was identified as a key
      requirement for cell-cell adhesions that permit collective migration.

PMID- 22361148
TI  - Brain development: neural signature predicts autism's emergence.
AB  - A new study has found that neural sensitivity to eye gaze in early infancy is
      associated with subsequent development of autism. This discovery provides a much
      needed biomarker for autism spectrum disorder prior to emergence of behavioral
      symptoms.

PMID- 22361149
TI  - Mitosis: short-circuiting spindle checkpoint signaling.
AB  - The spindle checkpoint forms an intricate signaling circuit to sense unattached
      kinetochores, to inhibit the anaphase-promoting complex/cyclosome (APC/C), and to
      delay anaphase onset. Using clever genetic experiments in the budding yeast, Lau
      and Murray define the endpoint of checkpoint signaling and provide key
      mechanistic insights into checkpoint inhibition of APC/C.

PMID- 22361150
TI  - Ecology: pollinator-plant synchrony tested by climate change.
AB  - Flowering plants could lose their pollination service if climate warming
      potentially uncouples timing of flowering from pollinator availability. Recent
      evidence might suggest this effect may be less than feared.

PMID- 22361151
TI  - Visuo-motor control: when the brain loses track of the eyes.
AB  - In single-units studies, neuronal signals are recorded to assess their
      significance and, hopefully, their role in controlling behavior. A new study of
      neuronal signals associated with eye position helps to explain not only how the
      system normally works, but also how it sometimes fails.

PMID- 22361152
TI  - Notch signaling: numb makes the difference.
AB  - During Drosophila sensory organ precursor cell development, Numb segregates
      asymmetrically and functions as a cell fate determinant. Recent work now
      demonstrates in vivo that Numb inactivates Notch by promoting its endocytosis.

PMID- 22361153
TI  - Evolution: why good dads win.
AB  - Males usually do not provide parental care and with good reason, they may be
      caring for the offspring of someone else. But there are cases of male-only care
      even when certainty of paternity is low: why? A new model suggests female choice
      may provide the answer.

PMID- 22361154
TI  - Wnt signaling: the many interfaces of beta-catenin.
AB  - Wnt signaling regulates virtually every cell fate decision during development.
      How can the same signal trigger such diverse events? Engaging different
      transcriptional machinery via different protein interfaces on the transcriptional
      co-activator beta-catenin provides part of the answer.

PMID- 22361155
TI  - New CuCl2-induced glucoside esters and other constituents from Portucala
      oleracea.
AB  - Two new glucoside esters 1 and 2 were produced as stress metabolites in the fresh
      leaves of Portulaca oleracea, in response to abiotic stress elicitation by
      CuCl(2). A new sugar ester (3) and two known compounds (4 and 5) were also
      isolated. Their structures were established by spectroscopic means. The
      antioxidative activities of stress metabolites and the related isolates were
      evaluated by DPPH assay. The results showed that new stress-driven adducts of
      monolignans and monoterpenes with a glucose bridge exhibited much stronger
      antioxidative activities than other compounds.

PMID- 22361157
TI  - A Rasch model analysis of technology usage in Minnesota hospitals.
AB  - PURPOSE: To identify whether the level of difficulty varied among various
      healthcare technologies. In addition, to examine the whether the degree of
      healthcare technology adoption was related to patient safety. METHODS: The data
      on healthcare technology usage came from a survey of hospitals in Minnesota.
      There were responses from individuals within 104 hospitals for an effective
      response rate of 72.7%. The data on patient safety was taken from the Hospital
      Compare database. Rasch model analysis and regression analysis were used to
      analyze the data. RESULTS: Rasch model analysis revealed that the difficulty of
      implementation of healthcare information technologies varied by the particular
      technology. That is, some technologies were more difficult than other
      technologies. Further, it was found that the degree of healthcare information
      technology implementation within a hospital was significantly related to patient
      safety. CONCLUSION: This study identified design and policy implications for
      hospital decision makers. In particular, it was shown that the technological
      capability of a hospital is a key consideration in determining the level of
      resources that are necessary to implement specific healthcare technologies within
      a hospital.

PMID- 22361156
TI  - Altered N-methyl-D-aspartate receptor function in reelin heterozygous mice: male
      female differences and comparison with dopaminergic activity.
AB  - The aim of this study was to investigate the in vivo relationship between reelin
      and NMDA receptor function in schizophrenia. We assessed the effect of reelin
      deficiency in behavioral models of aspects of this illness, NMDA receptor subunit
      levels, and NMDA receptor, dopamine D2 receptor, and dopamine transporter
      density. Male, but not female, reelin heterozygous mice showed significantly
      enhanced MK-801-induced locomotor hyperactivity compared to wildtype controls
      (7.4-fold vs. 5.2-fold effect of MK-801 over saline, respectively) but there were
      no genotype differences in the response to amphetamine. Both male and female
      reelin heterozygous mice showed enhanced effects of MK-801 on startle, but not
      prepulse inhibition (PPI) of startle. There were no group differences in the
      effect of apomorphine on startle or PPI. The levels of NMDA receptor subunits
      were not altered in the striatum. In the frontal cortex, male and female reelin
      heterozygous mice showed significant up-regulation of NR1 subunits, but down
      regulation of NR2C subunits, which was associated with significantly elevated
      NR1/NR2A and NR1/NR2C ratios. However, there were no differences in [3H]MK-801
      binding density in the nucleus accumbens or caudate nucleus, nor in the density
      of [3H]YM-09151 or [3H]GBR12935 in these brain regions. The enhanced effects of
      MK-801 in reelin heterozygous mice in this study could be reflective of the role
      of reelin deficiency in schizophrenia. This genotype effect was male-specific for
      locomotor hyperactivity, a model of psychosis, but was seen in male and female
      mice for startle, which could be an indication of changes in anxiety. Changes in
      NMDA receptor subunit levels and ratios were also seen in both male and female
      mice. These results suggest that the role of reelin deficiency in schizophrenia
      may be particularly mediated by altered NMDA receptor responses, with some of
      these effects being strictly sex-specific.

PMID- 22361158
TI  - Implementation and expansion of an electronic medical record for HIV care and
      treatment in Haiti: an assessment of system use and the impact of large-scale
      disruptions.
AB  - PURPOSE: System use is a key criterion of success in an electronic medical record
      (EMR) implementation, and there is little research on long-term use of systems
      following implementation. The aim of the paper was to describe the development,
      implementation and use of iSante, Haiti's national HIV care and treatment EMR.
      METHODS: To build a picture of the history of iSante, we interviewed 11 staff
      involved with the development and implementation of the EMR, and reviewed
      organization records. Data entry and report use were ascertained by querying the
      central patient database. RESULTS: By the end of 2010 there were 67 sites with
      iSante installed, and the scope of the system had been expanded to include
      primary care and obstetrics and gynecology. New functionality includes data forms
      specific to subpopulations, the ability to transfer patient records among
      clinics, and integration with an electronic laboratory system. We observed
      fluctuations in use over time, with substantial reductions in the number of
      active sites during times of large-scale disruptions in Haiti. A surge in report
      use following the January 2010 earthquake suggests that clinics found the EMR to
      be a valuable source of data during the recovery phase. CONCLUSION: There is real
      potential for EMRs in developing countries to improve clinical practice and make
      data available for efficient reporting, quality improvement and other population
      health uses. An approach of continuous system improvement, combined with regular
      assessments of use, is necessary for achieving an effective, national
      implementation of a standardized EMR. We have achieved successes in terms of
      rolling out new functionality and expanding to new sites, but more work remains
      to be done to improve perceptions of data quality and increase use of population
      data for accurate and timely reporting.

PMID- 22361159
TI  - Internet based patient pathway as an educational tool for breast cancer patients.
AB  - OBJECTIVE: The aim of this paper was to describe the process of developing an
      Internet-based empowering patient education program for breast cancer patients
      and to evaluate the quality of the program from the perspective of patients. In
      this program, the patient pathway was used as an educational tool. METHODS: The
      Breast Cancer Patient Pathway (BCPP) was developed and tested at one Finnish
      university hospital in 2005-2007. Thirty-eight newly diagnosed breast cancer
      patients used the program during their treatment process until the end of all
      treatments (average 9 months) in 2008-2010. After the treatments the patients
      evaluated the content, language and structure, instructiveness, external
      appearance and technical characteristics of the web site as subcategories with
      the Evaluating Internet Pages of Patient Education instrument, which is a 37-item
      Likert scale (1-4) questionnaire. Comparison between the subcategories was done
      with Friedman's test. Dependencies between demographic variables and evaluation
      values were tested with Pearson correlation coefficients. RESULTS: The mean value
      of all evaluation criteria was 3.40. However, patients' evaluations between
      different subcategories varied, being the highest in language and structure (mean
      3.48) and lowest in content (mean 3.13). Language and structure, external
      appearance and technical characteristics were significantly better than content,
      and language and structure better than instructiveness. Significant correlations
      were not found between demographic variables and evaluation values. CONCLUSIONS:
      Patients evaluated the quality of the BCPP to be best in language and structure
      and weakest in content. In terms of future development of the BCPP, the most
      improvement is needed in content and instructiveness. There is also a need for
      further development and study of Internet-based patient education.

PMID- 22361161
TI  - [Assessment of in vitro activity and stability of antifungal suspensions for
      mouthrinses: to a reappraisal of empiric practices?].
AB  - Establishment of an effective prophylaxis against oral candidiasis by local
      treatment is essential for immunocompromised patients. The aim of the study is to
      assess effectiveness and stability of antifungal suspensions for mouthrinses. The
      assessed suspensions are compounded by one solvent among sterile water, spring
      water or sodium bicarbonate associated with amphotericin B (Fungizone(r)) or
      nystatine (Mycostatine(r)). Two others mixes are assessed: Mycostatine(r)
      bicarbonate and Mycostatine(r)-Hextril(r)-bicarbonate as well as the two straight
      antifungal. In vitro activity is tested on five Candida species (C. albicans, C.
      glabrata, C. krusei, C. parapsilosis, C. tropicalis) after a five minutes contact
      between yeasts and the assessed suspension. A galenic study is realized during 3
      days. Mixes associating a polyene with sodium bicarbonate have no effectiveness
      on Candida albicans, others mixes shows intermediate effectiveness (the
      percentage of yeast growth inhibition lies between 35% and 68%). Effectiveness
      results of Hextril(r)-based mixes are not explainable because of alcohol in its
      composition. Spring water-based mixes must be evicted due to microbiologic
      contaminations after 48hours. Mycostatine(r)-Hextril(r)-bicarbonate mix is not
      stable during 3 days. All those mouthrinses, poorly effective, excepted on C.
      glabrata, should be avoided. Straight Mycostatine(r) shows a good antifungal
      effectiveness excepted on C. krusei and its use should be recommended.

PMID- 22361160
TI  - Molecular characterization of human calicivirus associated with acute diarrheal
      disease in Mexican children.
AB  - BACKGROUND: Human caliciviruses (HuCV) are emerging enteric pathogens that are a
      common cause of diarrhea in humans worldwide. Due to the paucity of information
      on the molecular characterization of HuCV circulating in Mexico, the aim of this
      work was to investigate the diversity and molecular epidemiology of the HuCV
      infection associated with acute diarrheal disease in Mexican children aged up to
      5 years. RESULTS: Of the 131/414 (32%) HuCV positive-specimens analyzed, 128 were
      identified as Norovirus (NoV) and three as Sapovirus (SaV). Of the NoV positive
      specimens, 118/128 (92%) were NoV GII and 10/128(8%) were untypeable by RT-PCR in
      both polymerase and capsid genes, whereas one SaV isolate was further confirmed
      by sequencing as GI.2. Phylogenetic analysis based on polymerase partial gene
      sequences from 89/131 (68%) HuCV isolates showed that 86/89 (97%) belong to NoV
      GII.4 with three main variant clusters of this genotype, 2/89 (2%) to NoV GII.2,
      and 1/89 (1%) to SaV GI.2. Furthermore, partial sequencing of the capsid gene VP1
      of 63/131 (48%) strains indicated that 61/63 (97%) correlated with NoV GII.4,
      whereas only 2/63 (3%) clustered to NoV GII.2. HuCV infections were detected
      throughout the year, and the highest number of cases positive for NoV was found
      in children between 7 and 18 months of age (60%). CONCLUSIONS: This study
      highlights the usefulness of analyzing both polymerase and capsid genes for
      molecular characterization of HuCV and demonstrates the relatedness and
      predominance of NoV GII.4 with acute diarrheal disease in young Mexican children,
      thus contributing to better understanding of the molecular epidemiology of this
      disease.

PMID- 22361162
TI  - Distribution of HLA class I and II genes in ankylosing spondylitis patients from
      Morocco.
AB  - OBJECTIVES: In Morocco, the patients affected by ankylosing spondylitis (AS)
      presents a high frequency of coxitis. Our study reports, for the first time, the
      polymorphism of Human Leukocyte Antigen (HLA) class I and class II molecules in
      the Moroccan patients. METHODS: Forty-six patients diagnosed with an AS and
      coxitis were compared to a group of 183 healthy controls matched by age, sex and
      ethnic origin. The HLA typing was performed using microlymphocytotoxicity for the
      class I (-A, -B) and PCR-SSP for the class II (-DR, -DQ). RESULTS: We found a
      significant increase of the HLA-B27 antigen frequency (P<0.0001, RR=20.9) in AS
      patients (29.3%) compared to the controls (3.2%) and a significant decrease in
      the frequency of HLA-B12 and HLA-B18 antigens. Examination of HLA class II
      distribution shows a significant increase of the HLA-DRB1*11 allele frequency in
      patients (P<0.0001). Concerning HLA-DQB1* alleles, no significant difference
      between patients and controls was appreciable. CONCLUSIONS: The HLA-B27 antigen
      is involved in the predisposition to the AS with coxitis in the Moroccan
      population. However, the low frequency observed in our population suggests the
      existence of other genetic and/or environmental factors. Other HLA genes seem to
      confer a predisposing effect (DRB*11) or a protective effect (B12 and B18)
      against the disease.

PMID- 22361163
TI  - Colorectal cancer: comparison of clinicopathologic features between Moroccans
      patients less than 50 years old and older.
AB  - INTRODUCTION: Colorectal cancer is a major public health problem. However, this
      cancer is usually developed on preexisting lesion. This makes this cancer
      accessible to a prevention strategy. OBJECTIVE: The aim of this study was to
      determine the clinicopathologic characteristics of patients under 50 years.
      PATIENTS AND METHODS: This study involved 133 patients with colorectal cancer
      recruited in CHU Ibn-Rochd, Casablanca. Data relating age, sex, stage at
      presentation, histological type and tumor location were obtained from the
      pathological and clinical records of each patient. Statistical analysis was
      performed to compare clinicopathological data in patients under 50 years and in
      older patients. RESULTS AND DISCUSSION: The average age of patients was 54 years.
      The frequency of patients aged 50 or under was 40.6% The tumors in the youngest
      age group were more often mucinous and signet ring cells (18.5%) versus (5.1%) in
      the oldest age group. The right colon was more often affected in the youngest age
      group, 38.9% versus 17.7% in the oldest age group (P=0.008). CONCLUSION: The
      proposition of colorectal cancer in subjects 50 or under was high in Morocco.
      Colorectal cancers in the youngest age group were more often mucinous or signet
      ring cells and was more often located in the right colon. We intend to complete
      this study by a genetic study to help improve prevention and care of young
      patient.

PMID- 22361164
TI  - Hypothermia attenuates the severity of oxidative stress development in
      asphyxiated newborns.
AB  - PURPOSE: This retrospective case-control study aimed to examine the development
      of oxidative stress in asphyxiated infants delivered at more than 37 weeks of
      gestation. MATERIAL AND METHODS: Thirty-seven neonates were stratified into 3
      groups: the first group experienced hypothermia (n = 6); the second received
      hypothermia cooling cup treatment for 3 days, normothermia (n = 16); and the
      third was the control group (n = 15). Serum total hydroperoxide (TH), biological
      antioxidant potential, and oxidative stress index (OSI) (calculated as
      TH/biological antioxidant potential) were measured within 3 hours after birth.
      RESULTS: Serum TH and OSI levels gradually increased after birth in hypothermia
      and normothermia cases. At all time points, serum TH and OSI levels were higher
      in hypothermia and normothermia cases than in control cases. Serum TH and OSI
      levels were higher in normothermia cases than in hypothermia cases at days 3, 5,
      and 7. CONCLUSION: This study demonstrated that hypothermia attenuated the
      development of systemic oxidative stress in asphyxiated newborns.

PMID- 22361165
TI  - Enhanced early-latency electromagnetic activity in the left premotor cortex is
      associated with successful phonetic categorization.
AB  - Sensory-motor interactions between auditory and articulatory representations in
      the dorsal auditory processing stream are suggested to contribute to speech
      perception, especially when bottom-up information alone is insufficient for
      purely auditory perceptual mechanisms to succeed. Here, we hypothesized that the
      dorsal stream responds more vigorously to auditory syllables when one is engaged
      in a phonetic identification/repetition task subsequent to perception compared to
      passive listening, and that this effect is further augmented when the syllables
      are embedded in noise. To this end, we recorded magnetoencephalography while
      twenty subjects listened to speech syllables, with and without noise masking, in
      four conditions: passive perception; overt repetition; covert repetition; and
      overt imitation. Compared to passive listening, left-hemispheric N100m equivalent
      current dipole responses were amplified and shifted posteriorly when perception
      was followed by covert repetition task. Cortically constrained minimum-norm
      estimates showed amplified left supramarginal and angylar gyri responses in the
      covert repetition condition at ~100ms from stimulus onset. Longer-latency
      responses at ~200ms were amplified in the covert repetition condition in the left
      angular gyrus and in all three active conditions in the left premotor cortex,
      with further enhancements when the syllables were embedded in noise. Phonetic
      categorization accuracy and magnitude of voice pitch change between overt
      repetition and imitation conditions correlated with left premotor cortex
      responses at ~100 and ~200ms, respectively. Together, these results suggest that
      the dorsal stream involvement in speech perception is dependent on perceptual
      task demands and that phonetic categorization performance is influenced by the
      left premotor cortex.

PMID- 22361167
TI  - The role of the left anterior temporal lobe in exception word reading:
      reconciling patient and neuroimaging findings.
AB  - Semantic dementia (SD) is a neurodegenerative disease that occurs following the
      atrophy of the anterior temporal lobes (ATLs). It is characterised by the
      degradation of semantic knowledge and difficulties in reading exception words
      (surface dyslexia). This disease has highlighted the role of the ATLs in the
      process of exception word reading. However, imaging studies in healthy subjects
      have failed to detect activation of the ATLs during exception word reading. The
      aim of the present study was to test whether the functional brain regions that
      mediate exception word reading in normal readers overlap those brain regions
      atrophied in SD. In Study One, we map the brain regions of grey matter atrophy in
      AF, a patient with mild SD and surface dyslexia profile. In Study Two, we map the
      activation pattern associated with exception word compared to pseudoword reading
      in young, healthy participants using fMRI. The results revealed areas of
      significant activation in healthy subjects engaged in the exception word reading
      task in the left anterior middle temporal gyrus, in a region observed to be
      atrophic in the patient AF. These results reconcile neuropsychological and
      functional imaging data, revealing the critical role of the left ATL in exception
      word reading.

PMID- 22361166
TI  - Dissociable large-scale networks anchored in the right anterior insula subserve
      affective experience and attention.
AB  - Meta-analytic summaries of neuroimaging studies point to at least two major
      functional-anatomic subdivisions within the anterior insula that contribute to
      the detection and processing of salient information: a dorsal region that is
      routinely active during attention tasks and a ventral region that is routinely
      active during affective experience. In two independent samples of cognitively
      normal human adults, we used intrinsic functional connectivity magnetic resonance
      imaging to demonstrate that the right dorsal and right ventral anterior insula
      are nodes in separable large-scale functional networks. Furthermore, stronger
      intrinsic connectivity within the right dorsal anterior insula network was
      associated with better performance on a task involving attention and processing
      speed whereas stronger connectivity within the right ventral anterior insula
      network was associated with more intense affective experience. These results
      support the hypothesis that the identification and manipulation of salient
      information is subserved by at least two brain networks anchored in the right
      anterior insula that exhibit distinct large-scale topography and dissociable
      behavioral correlates.

PMID- 22361168
TI  - State-dependent attention modulation of human primary visual cortex: a high
      density ERP study.
AB  - Converging electrophysiological and brain-imaging results show that sensory
      processing in V1 can be modulated by attention. In this study, we tested the
      prediction that this early filtering effect depends on the current affective
      state of the participant. We recorded visual evoked potentials (VEPs) to visual
      peripheral distractors while participants performed a demanding task at fixation,
      whose perceptual load was manipulated in a parametric fashion. Crucially, levels
      of negative affect were either increased or decreased independently of changes in
      perceptual load. Concurrent psychophysiological measurements and self-report
      scales confirmed that changes in emotional state were effective. In the control
      condition, ERP results showed that the C1 component generated in response to the
      exact same peripheral distractors systematically varied in amplitude with the
      amount of perceptual load imposed at fixation, being larger when perceptual load
      decreased. However, this early modulatory effect in V1 was disrupted when
      participants transiently experienced increased state anxiety, resulting in a
      decreased C1 amplitude even though task load at fixation remained low. These
      results suggest that early bottom-up processing in V1 is not only influenced by
      the amount of attention resources available, but also by the current internal
      state of the participant.

PMID- 22361169
TI  - Neural correlates of feigned memory impairment are distinguishable from answering
      randomly and answering incorrectly: an fMRI and behavioral study.
AB  - Previous functional magnetic resonance imaging (fMRI) studies have identified
      activation in the prefrontal-parietal-sub-cortical circuit during feigned memory
      impairment when comparing with truthful telling. Here, we used fMRI to determine
      whether neural activity can differentiate between answering correctly, answering
      randomly, answering incorrectly, and feigned memory impairment. In this study, 12
      healthy subjects underwent block-design fMRI while they performed digit task of
      forced-choice format under four conditions: answering correctly, answering
      randomly, answering incorrectly, and simulated feigned memory impairment. There
      were three main results. First, six areas, including the left prefrontal cortex,
      the left superior temporal lobe, the right postcentral gyrus, the right superior
      parietal cortex, the right superior occipital cortex, and the right putamen, were
      significantly modulated by condition type. Second, for some areas, including the
      right superior parietal cortex, the right postcentral gyrus, the right superior
      occipital cortex, and the right putamen, brain activity was significantly greater
      in feigned memory impairment than answering randomly. Third, for the areas
      including the left prefrontal cortex and the right putamen, brain activity was
      significantly greater in feigned memory impairment than answering incorrectly. In
      contrast, for the left superior temporal lobe, brain activity was significantly
      greater in answering incorrectly than feigned memory impairment. The results
      suggest that neural correlates of feigned memory impairment are distinguishable
      from answering randomly and answering incorrectly in healthy subjects.

PMID- 22361170
TI  - Left ventricular function quantified by myocardial strain imaging in small-breed
      dogs with chronic mitral regurgitation.
AB  - BACKGROUND: The presence of left ventricular (LV) systolic dysfunction may
      influence prognosis or therapy in dogs with chronic mitral regurgitation (MR).
      Assessment of LV function in MR by conventional echocardiography is confounded by
      altered ventricular loading. Myocardial deformation (strain) imaging might offer
      more sensitive estimates of LV function in this disease. OBJECTIVE: Prospectively
      measure myocardial strain in dogs with asymptomatic MR compared to a control
      group. ANIMALS, MATERIALS AND METHODS: Forty healthy dogs (3.5-11.5 kg): 20
      Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this
      study. LV size and function were assessed in a short-axis plane. Segmental radial
      strain and strain rate and global circumferential strain were measured using a 2D
      echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared
      using Bonferroni t-tests. Influences of heart rate and body weight were explored
      with linear regression. RESULTS: The MR group had significantly greater mean
      values for heart rate, LV size, and LV systolic function. Specifically, LV
      diastolic diameter, diastole area, shortening fraction, averaged peak systolic
      and early diastolic radial strain, global circumferential strain, and averaged
      radial strain rate were significantly greater in the MR group (p < 0.015 to p <
      0.001). Strain was unrelated to weight, but weakly correlated with heart rate.
      CONCLUSIONS: Similar to conventional indices, Stage B2 dogs with MR demonstrate
      hyperdynamic deformation in the short-axis plane. Short-axis strain variables
      measured by 2D speckle tracking are greater than for controls of similar age and
      weight. These results imply either preserved LV systolic function or that LV
      dysfunction is masked by altered ventricular loading.

PMID- 22361171
TI  - Post-mortem evaluation of expanded polytetrafluoroethylene (ePTFE) used in mitral
      valve repair in dogs.
AB  - Mitral valve repair is one of the treatment options for mitral regurgitation.
      Expanded polytetrafluoroethylene (ePTFE) is a polymer that has been widely used
      in cardiovascular surgery. In this case series, we report the autopsy and
      histological findings in 6 dogs that underwent cardiopulmonary bypass for mitral
      annuloplasty using ePTFE sheets and chordoplasty using ePTFE sutures. From May
      2005 to October 2009, 3 female and 3 male dogs with severe mitral regurgitation
      underwent mitral valve repair. This case series included 3 Cavalier King Charles
      spaniels, 2 Maltese, and 1 Shih Tzu. The survival period after surgery was 19-72
      (35 +/- 19) months. In all the cases, autopsy revealed that the ePTFE sheets and
      sutures were not damaged and well integrated into the surrounding highly
      differentiated, connective tissues. Low-power microscopy revealed that in all
      cases, the tissues surrounding the ePTFE sheet in the mitral valve annulus had
      almost completely been covered by granulation tissue. No inflammatory infiltrate
      or thrombogenesis was observed around the ePTFE in any of the cases. There was no
      evidence of reactive changes in the region surrounding the ePTFE. These results
      suggest that ePTFE has excellent tissue compatibility and durability and can be
      effectively used for canine mitral valve repair.

PMID- 22361173
TI  - Preparation, spectroscopic and thermal characterization of new metal complexes of
      verlipride drug. In vitro biological activity studies.
AB  - Metal complexes of the general formula [M(VER)(2)Cl(2)(H(2)O)(2)].yH(2)O and
      [Cr(VER)(2)Cl(2)(H(2)O)(2)]Cl.H(2)O (where VER=verlipride, M=Mn(II) (y=2), Co(II)
      (y=2), Ni(II) (y=2), Cu(II) (y=1) and Zn(II) (y=0)) are prepared and
      characterized based on elemental analyses, IR, (1)H NMR, magnetic moment, molar
      conductance, and thermal analyses (TG and DTA) techniques. From the elemental
      analyses data, the complexes are formed in 1:2 [Metal]:[VER] ratio. The molar
      conductance data reveal that all the metal chelates are non-electrolytes except
      Cr(III) complex, it is 1:1 electrolyte. IR spectra show that VER is coordinated
      to the metal ions in a neutral monodentate manner with O donor site of the
      carbonyl O atom. On the basis of spectral studies and magnetic moment
      measurements an octahedral geometry has been assigned for the complexes. The
      thermal behavior of these chelates is studied using thermogravimetric analysis
      technique. The results obtained show that the complexes lose hydrated water, HCl
      and coordinated water molecules followed immediately by decomposition of the
      ligand molecules in the successive unseparate steps. The VER drug, in comparison
      to its metal complexes is also screened for its biological activity against Gram
      positive bacterial (Staphylococcus aureus) and Gram negative bacteria
      (Escherichia coli) and fungi (Candida albicans and Aspergillus flavus) in vitro.
      The activity data show that most of the metal complexes have antibacterial
      activity like or higher than that of the parent VER drug against one or more
      species.

PMID- 22361172
TI  - REGgamma is associated with multiple oncogenic pathways in human cancers.
AB  - BACKGROUND: Recent studies suggest a role of the proteasome activator, REGgamma,
      in cancer progression. Since there are limited numbers of known REGgamma targets,
      it is not known which cancers and pathways are associated with REGgamma. METHODS:
      REGgamma protein expressions in four different cancers were investigated by
      immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO)
      database search, microarray platform validation, differential expressions of
      REGgamma in corresponding cancers were statistically analyzed. Genes highly
      correlated with REGgamma were defined based on Pearson's correlation coefficient.
      Functional links were estimated by Ingenuity Core analysis. Finally, validation
      was performed by RT-PCR analysis in established cancer cell lines and IHC in
      human colon cancer tissues RESULTS: Here, we demonstrate overexpression of
      REGgamma in four different cancer types by micro-tissue array analysis. Using
      meta-analysis of publicly available microarray databases and biological studies,
      we verified elevated REGgamma gene expression in the four types of cancers and
      identified genes significantly correlated with REGgamma expression, including
      genes in p53, Myc pathways, and multiple other cancer-related pathways. The
      predicted correlations were largely consistent with quantitative RT-PCR analysis.
      CONCLUSIONS: This study provides us novel insights in REGgamma gene expression
      profiles and its link to multiple cancer-related pathways in cancers. Our results
      indicate potentially important pathogenic roles of REGgamma in multiple cancer
      types and implicate REGgamma as a putative cancer marker.

PMID- 22361174
TI  - CD19(+)CD1d(+)CD5(+) B cell frequencies are increased in patients with
      tuberculosis and suppress Th17 responses.
AB  - Although the importance of B cells in the host immune response upon Mycobacterium
      tuberculosis infection has been recognized, a conclusive role for B cells has yet
      to be determined. In the present study, we found that primary CD19(+) B cells
      isolated from patients with tuberculosis significantly inhibited Th17, but not
      Th1, cell activation. Moreover, the suppressive activity was mediated by a
      CD19(+)CD1d(+)CD5(+) B cell population. Notably, patients with tuberculosis were
      found to have significantly higher frequencies of CD19(+)CD1d(+)CD5(+) B cells
      with stronger suppressive activity than such cells from healthy donors.
      Furthermore, the frequency of CD19(+)CD1d(+)CD5(+) B cells in peripheral blood
      was inversely correlated with that of Th17 cells in patients with tuberculosis.
      This finding that B cells negatively regulate Th17 responses provides a novel
      mechanism in the regulation of CD4(+) T cell responses-aside from regulatory T
      cells-during M. tuberculosis infection, which may impact the clinical outcome of
      tuberculosis.

PMID- 22361175
TI  - High dose lipopolysaccharide triggers polarization of mouse thymic Th17 cells in
      vitro in the presence of mature dendritic cells.
AB  - Lipopolysaccharide (LPS) plays an important role in the activation of innate
      immune cells, leading to secretion of proinflammatory factors and bridging the
      adaptive immune system. Exposing total mouse thymic cells culture to LPS induced
      a unique expression profile of cytokines (IL-17A, IL-17F, and IL-22) and the
      essential ROR-gammat master transcription factor, which suggested a preferential
      differentiation of thymocytes towards the Th17 cell phenotype. Th17-polarizing
      molecules (IL-23, IL-23R, IL-6, and TGF-beta) and IL-17A(+)CD4(+) thymocytes were
      also specifically produced by the in vitro LPS-stimulation of thymic cells.
      Furthermore, both the expression of Th17 differentiation-related molecules and
      the frequency of Th17 cells were significantly up-regulated with increasing doses
      of LPS, as evidenced by quantitative RT-PCR and flow cytometric analysis,
      respectively. The expressions and frequency reached maximum levels when LPS
      exposure had been maintained at an extremely high concentration (100 MUg/mL) for
      48 h. On the other hand, depletion of thymic dendritic cells (DCs) blocked the
      LPS-induced polarization of thymus-derived Th17 cell lineage. Addition of bone
      marrow-derived DCs (BMDCs) to the purified immature CD4(+) CD62L(low) thymocytes
      culture recovered the switch towards Th17 cells, which synergistically prompted
      the cytotoxic activity of CD8(+) T cells. Taken together, our data indicates that
      high doses of LPS can promote the differentiation of mouse thymus-derived Th17
      cells by a mechanism involving components associated with mature DCs.

PMID- 22361176
TI  - HMGB-1 induces cell motility and alpha5beta1 integrin expression in human
      chondrosarcoma cells.
AB  - Chondrosarcoma is a type of highly malignant tumor with a potent capacity to
      invade locally and cause distant metastasis. High mobility group box chromosomal
      protein 1 (HMGB)-1 is a widely studied, ubiquitous nuclear protein that is
      present in eukaryotic cells, and plays a crucial role in inflammatory response.
      However, the effects of HMGB-1 on human chondrosarcoma cells are largely unknown.
      In this study, we found that HMGB-1 increased the migration and the expression of
      alpha5beta1 integrin in human chondrosarcoma cells. Transfection of cells with
      receptor for advanced glycation end products (RAGE) receptor siRNA reduced HMGB-1
      induced cell migration and integrin expression. Activations of
      phosphatidylinositol 3-kinase (PI3K), Akt, and AP-1 pathways after HMGB-1
      treatment were demonstrated, and HMGB-1-induced expression of integrin and
      migration activity was inhibited by the specific inhibitor and mutant of PI3K,
      Akt, and AP-1 cascades. Taken together, our results indicated that HMGB-1
      enhances the migration of chondrosarcoma cells by increasing alpha5beta1 integrin
      expression through the RAGE receptor/PI3K/Akt/c-Jun/AP-1 signal transduction
      pathway.

PMID- 22361177
TI  - Medicinal foods from marine animals: current status and prospects.
AB  - The lifestyle of human being is changing day by day toward the simplified and
      more convenient way of living. Human wellbeing is majorly dependent on the daily
      food habits that are in accordance with the habits of individual community and
      the surrounding environments. Although the food habits are simplified and
      fashioned according to the current lifestyle, many of the Asians are still
      showing much importance to the naturally derived and traditional foods. One such
      medicinally important natural source is the foods from marine organisms, which
      are an important growing notion for the development of marine nutraceuticals and
      functional foods. In this context, we have already brought the recent trends and
      applications of marine algal (macro and micro) foods in my previous volume. The
      current preliminary chapter of this book volume on marine animals and microbes
      describes about the prospects of various marine animals and their derived
      substances/materials as medicinal foods. In addition, this chapter encourages the
      new researchers as well as various health communities to implement the marine
      animal-based medicinal foods and their applications.

PMID- 22361178
TI  - Nutraceutical functionalities of polysaccharides from marine invertebrates.
AB  - Many researchers are seeking functional materials from marine resources. These
      marine resources can be used as traditional food additives, and specifically,
      these are based on polysaccharides. To date, there is a big opportunity to
      develop new high-value added products with indispensable functional
      characteristics, which can be used in nutraceuticals either as additives or
      supplements. Also, a crossover in the pharmaceutical market may be established.
      Some glycosaminoglycans (GAGs) mimetic-type molecules are already being utilized
      in the field of nutrition as well as in the cosmetics industry. This chemical is
      used as a dietary supplement to maintain the structure and function of
      cartilages, for the relief of pain caused by osteoarthritic joints, and can also
      be used as an anti-inflammatory agent. Recently, in relation to the prevalence of
      mad cow disease and avian influenza, the production of GAGs from marine
      invertebrates offers new market opportunities as compared with that obtained from
      bovine or avian livestock.

PMID- 22361179
TI  - Marine by-product phospholipids as booster of medicinal compounds.
AB  - Marine phospholipids are defined as phospholipids containing docosahexaenoic acid
      (DHA) or eicosapentaenoic acid that would be more effective than fish oil, which
      is mostly composed of triacylglycerol, in exerting health benefits. Marine
      phospholipids would boost the effect of both the health-beneficial hydrophilic
      and the hydrophobic compounds such as cell differentiators, anticancer compounds,
      and antiobesity compounds. When marine phospholipids are served as liposomal
      drinks, they would be more effective than adding into solid foods or feeds. As
      long as the liposome bilayer is basically composed of marine phospholipids, they
      would promote the encapsulated functional compounds. And this is the principal
      advantage of choosing marine phospholipids as liposomal membrane. Bioconversion
      of marine phospholipid would also be advantageous in delivering DHA into the
      desired tissue. For example, lysophosphatidylserine obtained through
      phospholipase D-mediated transphosphatidylation and phospholipase A1 or sn-1
      positional specific lipase-mediated partial hydrolysis seemed to be the most
      effective chemical form in delivering DHA into brain.

PMID- 22361180
TI  - Characterization of bioactive peptides obtained from marine invertebrates.
AB  - Bioactive peptides as products of hydrolysis of diverse marine invertebrate
      (shellfish, crustacean, rotifer, etc.) proteins are the focus of current
      research. After much research on these muscles and by-products, some biologically
      active peptides were identified and applied to useful compounds for human
      utilization. This chapter reviews bioactive peptides from marine invertebrates in
      regarding to their bioactivities. Additionally, specific characteristics of
      antihypertensive, anti-Alzheimer, antioxidant, antimicrobial peptide enzymatic
      production, methods to evaluate bioactivity capacity, bioavailability, and safety
      concerns of peptides are reviewed.

PMID- 22361181
TI  - Bioactive marine peptides: nutraceutical value and novel approaches.
AB  - Marine organisms represent a valuable source of nutraceuticals and functional
      compounds. The biodiversity of the marine environment and the associated chemical
      diversity constitute a practically unlimited resource of novel active substances
      for the development of bioactive products. Recently, a great deal of interest has
      been expressed in marine-derived bioactive peptides because of their numerous
      beneficial health effects. Moreover, several studies have reported that marine
      bioactive peptides can be used as antihypertensive, antioxidative, anticoagulant,
      and antimicrobial components in functional foods or nutraceuticals and
      pharmaceuticals due to their therapeutic potential in the treatment or prevention
      of disease. In this chapter, we provide an overview of bioactive peptides derived
      from marine organisms as well as information about their biological properties
      and mechanisms of action with potential applications in different areas.

PMID- 22361182
TI  - Chitosan and fish collagen as biomaterials for regenerative medicine.
AB  - This chapter focuses and reviews on the characteristics and biomedical
      application of chitosan and collagen from marine products and advantages and
      disadvantages of regeneration medicine. The understanding of the production
      processes of chitosan and collagen and the conformation of these biomaterials are
      indispensable for promoting the theoretical and practical availability. The
      initial inflammatory reactions associated with chitosan application to hard and
      soft tissues need to be controlled before it can be considered for clinical
      application as scaffold. Further, as chitosan takes too long for biodegradation
      in vivo, generally it is not suitable for the scaffold for degenerative medicine
      in especially dental pulp tissue. The collagen extract from the scales of
      tropical fish has been reported to have a degeneration temperature of 35 degrees
      C. The properties of biocompatibility and biodegradation of fish atelocollagen
      are suitable for the scaffold in regenerative medicine.

PMID- 22361183
TI  - Chitosan as potential marine nutraceutical.
AB  - Chitosan, the most abundant marine mucopolysaccharide, is derived from chitin by
      alkaline deacetylation, and possesses versatile biological properties such as
      biocompatibility, biodegradability, and a non-toxic nature. Due to these
      characteristics, considerable attention has been given to its industrial
      applications in the food, pharmaceutical, agricultural, and environmental
      industries. Currently, chitosan can be considered as a potential marine
      nutraceutical because its remarkable biological activities have been investigated
      and reported, in order to exploit its nutraceutical properties. This chapter,
      therefore, reviews the biological activities of chitosan including antioxidant,
      hypocholesterolemic, antimicrobial, and anti-inflammatory activities, as well as
      its mode of action in each activity.

PMID- 22361184
TI  - Bioactive compounds from marine sponges and their symbiotic microbes: a potential
      source of nutraceuticals.
AB  - Sponges are considered as the chemical factory in marine environment because of
      its immense production of chemically diverse compounds. Other than the chemical
      diversity, these compounds possess remarkable bioactivities. This great potential
      has aroused applications of sponge-derived compounds as therapeutics and at
      present, a number of promising compounds are in clinical and preclinical trials.
      Recently, nutraceuticals have received considerable interest among the health
      conscious community because of its multiple therapeutic effects. Natural health
      promoting substances gain continuous popularity as nutraceuticals due to its
      reduced risk of side effects. This overview discusses the potentials of marine
      sponge-derived bioactivities as natural health-promoting compounds.

PMID- 22361185
TI  - Medicinal benefits of marine invertebrates: sources for discovering natural drug
      candidates.
AB  - Marine invertebrates are one of the major groups of organisms, which could be
      diversified under the major taxonomic groups of Porifera, Cnidaria, Mollusca,
      Arthropoda, Echinodermata, and many other minor phyla. To date, range of
      medicinal benefits and a significant number of marine natural products (MNPs)
      have been discovered from marine invertebrates. Seafood diet from edible marine
      invertebrates such as mollusks and crustaceans has been linked with various
      medicinal benefits to improve human health. Among marine invertebrates, spongers
      from phylum Porifera is the most dominant group responsible for discovering large
      number of MNPs, which have been used as template to develop therapeutic drugs.
      MNPs isolated from invertebrates have shown wide range of therapeutic properties
      including antimicrobial, antioxidant, antihypertensive, anticoagulant,
      anticancer, anti-inflammatory, wound healing and immune modulator, and other
      medicinal effects. Therefore, marine invertebrates are rich sources of chemical
      diversity and health benefits for developing drug candidates, cosmetics,
      nutritional supplements, and molecular probes that can be supported to increase
      the healthy life span of human.

PMID- 22361186
TI  - Sea-originated cytotoxic substances.
AB  - Cancer accounted for huge number of deaths, which represents about 13% of all
      deaths worldwide, and the number of the deaths due to cancer is increasing.
      Natural products and their synthetic analogs are widely used as antitumor drugs.
      As represented by these drugs, many anticancer drugs originated from cytotoxic
      compounds. Marine natural products are a gold mine of strong bioactive compounds
      with unique structures created in evolution of organisms over hundred million
      years. However, in the field of drug discovery, most studies have focused on
      plant essences and bacterial metabolites, and candidate compounds from marine
      origin are still remaining relatively unexplored.

PMID- 22361187
TI  - Secondary metabolites with new medicinal functions from marine organisms.
AB  - We have focused on the identification of natural key compounds that possess
      biologically and medicinally intriguing functions. Some of bioactive naturally
      occurring compounds isolated from marine organisms were found to possess unique
      biological activities. Halichlorine from the marine sponge Halichondria okadai
      was shown to inhibit the activity of nuclear factor-kappaB in endothelial cells
      and block L-type Ca2+ channels. Thus, it may have therapeutic potentials for
      diseases such as atherosclerosis and hypertension.

PMID- 22361188
TI  - Structure-function relationship of anticoagulant and antithrombotic well-defined
      sulfated polysaccharides from marine invertebrates.
AB  - Marine sulfated polysaccharides (MSPs), such as sulfated fucans (SFs), sulfated
      galactans (SGs), and glycosaminoglycans (GAGs) isolated from invertebrate
      animals, are highly anionic polysaccharides capable of interacting with certain
      cationic proteins, such as (co)-factors of the coagulation cascade during
      clotting-inhibition process. Primarily, these molecular complexes between MSPs
      and coagulation-related proteins seem to be driven mostly by electrostatic
      interactions. However, through a systematic comparison using several novel well
      defined sulfated polysaccharides composed of repetitive oligosaccharides with
      clear sulfation patterns, it was proved that those molecular interactions are
      essentially regulated by the stereochemistry of the glycans (which depends on a
      conjunction of anomeric configurations, sugar types, conformational preferences,
      glycosylation, and sulfation sites), rather than just a mere consequence of the
      electronegative density charges (mainly from number of sulfate groups). Here, we
      present an overview about the structure-function relationship of the invertebrate
      MSPs with regular structures as potential anticoagulant and antithrombotic
      agents, as pathologies related to the cardiovascular system are one of the major
      causes of mortality in the world.

PMID- 22361189
TI  - Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and
      docosahexaenoic acid.
AB  - Marine-based fish and fish oil are the most popular and well-known sources of n-3
      polyunsaturated fatty acids (PUFAs), namely, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). These n-3 PUFAs are known to have variety of health
      benefits against cardiovascular diseases (CVDs) including well-established
      hypotriglyceridemic and anti-inflammatory effects. Also, various studies indicate
      promising antihypertensive, anticancer, antioxidant, antidepression, antiaging,
      and antiarthritis effects. Moreover, recent studies also indicate anti
      inflammatory and insulin-sensitizing effects of these fatty acids in metabolic
      disorders. Classically, n-3 PUFAs mediate some of these effects by antagonizing n
      6 PUFA (arachidonic acid)-induced proinflammatory prostaglandin E2 (PGE2)
      formation. Another well-known mechanism by which n-3 PUFAs impart their anti
      inflammatory effects is via reduction of nuclear factor-kappaB activation. This
      transcription factor is a potent inducer of proinflammatory cytokine production,
      including interleukin 6 and tumor necrosis factor-alpha, both of which are
      decreased by EPA and DHA. Other evidence also demonstrates that n-3 PUFAs repress
      lipogenesis and increase resolvins and protectin generation, ultimately leading
      to reduced inflammation. Finally, beneficial effects of EPA and DHA in insulin
      resistance include their ability to increase secretion of adiponectin, an anti
      inflammatory adipokine. In summary, n-3 PUFAs have multiple health benefits
      mediated at least in part by their anti-inflammatory actions; thus their
      consumption, especially from dietary sources, should be encouraged.

PMID- 22361190
TI  - Biological importance and applications of squalene and squalane.
AB  - Squalene is a polyunsaturated hydrocarbon with a formula of C30H50. Squalene can
      be found in certain fish oils, especially shark liver oil, in high amounts and
      some vegetable oils in relatively smaller amounts. Human sebum also contains 13%
      squalene as one of its major constituents. Squalane is a saturated derivative of
      squalene and also found in these sources. Interest in squalene has been raised
      after its characterization in shark liver oil which is used as a traditional
      medicine for decades. Several studies exhibited results that prove certain
      bioactivities for squalene and squalane. Up to date, anticancer, antioxidant,
      drug carrier, detoxifier, skin hydrating, and emollient activities of these
      substances have been reported both in animal models and in vitro environments.
      According to promising results from recent studies, squalene and squalane are
      considered important substances in practical and clinical uses with a huge
      potential in nutraceutical and pharmaceutical industries.

PMID- 22361191
TI  - Development of bioactive peptides from fish proteins and their health promoting
      ability.
AB  - Great amount of marine fish species have been identified with potential
      nutraceutical and medicinal values. Consequently, a number of bioactive compounds
      have been identified including fish muscle proteins, peptides, collagen and
      gelatin, fish oil, fish bone. Bioactive peptides derived from various fish muscle
      proteins have shown various biological activities including antihypertensive,
      antibacterial, anticoagulant, anti-inflammatory, and antioxidant activities, and
      hence they may be a potential material for biomedical and food industries.
      Further, they are commonly used in medical and pharmaceutical industries as
      carrier molecules for drugs, proteins, and genes. Hence, fish muscle protein
      derived peptides are valuable natural resources that can be potential material
      for biomedical, nutraceutical, and food industries.

PMID- 22361192
TI  - Marine fish-derived bioactive peptides as potential antihypertensive agents.
AB  - Hypertension is the most widespread risk factor for many serious cardiovascular
      diseases. Angiotensin-converting enzyme (ACE) plays a crucial role in
      cardiovascular physiological regulation by converting angiotensin I to a potent
      vasoconstrictor, angiotensin II. Hence, the inhibition of ACE is a key target for
      antihypertensive activity. Recently, potent antihypertensive peptides have been
      purified widely by enzymatic hydrolysis of muscle protein, skin collagen, and
      gelatin of many different kinds of marine fishes. Marine fish-derived bioactive
      peptides can be developed as antihypertensive components in functional foods or
      nutraceuticals. This contribution presents an overview of the ACE inhibitory
      peptides derived from marine fishes and discusses their future prospects to be
      used as potential drug candidates for preventing and treating high blood
      pressure.

PMID- 22361193
TI  - Bioactive sterols from marine resources and their potential benefits for human
      health.
AB  - Bioactive agents from marine resources have shown their valuable health
      beneficial effects. Therefore, increase knowledge on novel functional ingredients
      with biological activities from marine animal and microbe has gained much
      attention. Sterols are recognized as potential in development functional food
      ingredients and pharmaceutical agents. Marine resources, with a great diversity,
      can be a very interesting natural resource of sterols. This chapter focuses on
      biological activities of marine animal and microbe sterols with potential health
      beneficial applications in functional foods and pharmaceuticals.

PMID- 22361194
TI  - Therapeutic drugs: healing power of marine fish.
AB  - Marine fish is a major source of high-quality protein, lipids, and a wide variety
      of vitamins and minerals. These macromolecules and their derivatives show
      different pharmacological activities, which make the fish as a therapeutic diet.
      Modern technology has made it easy to explore the therapeutic importance of fish
      based diet on cardiovascular diseases, neurodegenerative diseases, radicals
      mediated diseases, and cancer. In this review, we focus on exploration of
      proteins, lipids, carbohydrates, minerals, and their derivatives from marine fish
      as a major source for bioactive compounds and their medicinal importance.

PMID- 22361195
TI  - Beneficial effect of teleost fish bone peptide as calcium supplements for bone
      mineralization.
AB  - A most common and trusted source of Ca is milk or other dairy products. However,
      some oriental people do not drink milk due to lactose indigestion and
      intolerance, which make them allergic to milk. There have been many studies on
      alternative calcium-rich diet or Ca supplements. Among them, teleost fish like
      anchovy and mola, which are commonly consumed in Asian countries, could be an
      important Ca dietary supplement, especially in population groups with low intakes
      of milk and dairy products. In this chapter, we summarize beneficial effects of
      teleost fish bone peptide (FBP) for Ca bioavailability and bone mineralization,
      based on our researches.

PMID- 22361196
TI  - Triterpene glycosides from sea cucumbers and their biological activities.
AB  - Triterpenoid glycosides are abundantly present in sea cucumbers, which are
      responsible for the toxicity of these echinoderms. More than 100 triterpenoid
      glycosides have been isolated in the past 20 years and those are grouped into
      four main structural categories considering their aglycone structure: 3beta
      hydroxyholost-9(ll)-ene aglycone skeleton, 3beta-hydroxyholost-7-ene skeleton,
      other holostane type aglycones and nonholostane aglycone. Most of the
      triterpenoid glycosides are found to be possessing potential biological
      activities. Among the biological activities, anticancer activity and antiviral
      activity are the most widely studied areas. In this communication, we have
      presented a general view of the structural characteristics of triterpenoid
      glycosides and their major biological activities. The structural significance and
      the application limitations of triterpene glycosides are also discussed.

PMID- 22361197
TI  - Chitooligosaccharides as potential nutraceuticals: production and bioactivities.
AB  - Chitooligosaccharide (COS), a derivative of chitosan, can be produced by either
      chemical or enzymatic hydrolysis. Looking back through past research, several
      technological approaches have been taken to prepare COSs, and enzymatic
      approaches are favorable due to their environmentally friendly methods, safety,
      and a lack of toxicity. Similar to chitosan, COSs can also be considered
      potential nutraceuticals due to their versatile biological activities, water
      soluble properties, and absorption properties in the intestine. Therefore, this
      chapter provides certain methods for the preparation of COSs and addresses their
      biological properties such as antihypertensive, antioxidant, antitumor,
      antimicrobial, and other select biological activities.

PMID- 22361198
TI  - Biological activities of glucosamine and its related substances.
AB  - Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans.
      We revealed that among GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and
      uronic acids (d-glucuronic acid and d-galacturonic acid), only GlcN induces the
      production of hyaluronic acid (HA) by synovial cells and chondrocytes, and the
      production level is much higher (>10-fold) in synovial cells compared with
      chondrocytes. Moreover, GlcN increases the expression of HA-synthesizing enzymes
      (HAS) in synovial cells and chondrocytes. These observations indicate that GlcN
      likely exhibits the chondroprotective action on OA by modulating the expression
      of HAS and inducing the production of HA (a major component of glycosaminoglycans
      contained in the synovial fluid) especially by synovial cells. The pathological
      change of subchondral bone is implicated in the initiation and progression of
      cartilage damage in OA. Thus, we further determined the effect of GlcN on the
      bone metabolism (osteoblastic cell differentiation). The results indicated that
      GlcN increases the mineralization of mature osteoblasts and the expression of
      middle and late stage markers (osteopontin and osteocalcin, respectively) during
      osteoblastic differentiation, and reduces the expression of receptor activator of
      NF-kappaB ligand (RANKL), a differentiation and activation factor for
      osteoclasts. These observations likely suggest that GlcN has a potential to
      induce the osteoblastic cell differentiation and suppress the osteoclastic cell
      differentiation, thereby increasing bone matrix deposition and decreasing bone
      resorption to modulate bone metabolism in OA.

PMID- 22361199
TI  - Development of marine probiotics: prospects and approach.
AB  - The term probiotics stands for bacterial strain acting for the upliftment of
      beneficial gut microflora as well as restricting the growth of decay or disease
      causing bacteria and other agents. They protect us from disease causing
      microorganisms and are vital for the digestion of nutrients and food. Researchers
      are now trying to explore the possibilities of therapeutic applications of
      probiotics in inflammatory bowel disease, treating diarrhea, eczema prevention in
      children, and reducing bladder cancer recurrence and urinary tract infections.
      The best known probiotic strains are Bifidobacteria, Lactobacilli, and
      Streptococcus thermophilus and can be found in food products such as yoghurts,
      fermented and unfermented milk, miso, tempeh, and some juices and soy beverages.
      Thus, as a substitute to the use of antibiotics, the dietary supplementation with
      probiotic bacteria is being widely employed in the aquaculture industry. This
      chapter is an attempt to shift the paradigm of research in probiotic area to the
      marine environment and to find ways of expanding the research in marine
      probiotics development.

PMID- 22361200
TI  - Bioactive secondary metabolites from marine microbes for drug discovery.
AB  - The isolation and extraction of novel bioactive secondary metabolites from marine
      microorganisms have a biomedical potential for future drug discovery as the
      oceans cover 70% of the planet's surface and life on earth originates from sea.
      Wide range of novel bioactive secondary metabolites exhibiting pharmacodynamic
      properties has been isolated from marine microorganisms and many to be
      discovered. The compounds isolated from marine organisms (macro and micro) are
      important in their natural form and also as templates for synthetic modifications
      for the treatments for variety of deadly to minor diseases. Many technical issues
      are yet to overcome before wide-scale bioprospecting of marine microorganisms
      becomes a reality. This chapter focuses on some novel secondary metabolites
      having antitumor, antivirus, enzyme inhibitor, and other bioactive properties
      identified and isolated from marine microorganisms including bacteria,
      actinomycetes, fungi, and cyanobacteria, which could serve as potentials for drug
      discovery after their clinical trials.

PMID- 22361201
TI  - Marine bacterial sources of bioactive compounds.
AB  - Thousands of novel compounds have been isolated from various marine bacteria and
      tested for pharmacological properties, many of which are commercially available.
      Many more are being tested as potential bioactive compound at the preclinical and
      clinical stages. The growing interest in marine-derived antiviral compounds,
      along with the development of new technology in marine cultures and extraction,
      will significantly expedite the current exploration of the marine environment for
      compounds with significant pharmacological applications, which will continue to
      be a promising strategy and new trend for modern medicine. Marine actinomycetes
      and cyanobacteria are a prolific but underexploited source for the discovery of
      novel secondary metabolites.

PMID- 22361202
TI  - Biological activities and health effects of terpenoids from marine fungi.
AB  - Recently, a great deal of interest has been developed by the consumers toward
      natural bioactive compounds as functional ingredients in the nutraceutical,
      cosmeceutical, and pharmaceutical products due to their various health beneficial
      effects. Hence, it can be suggested that bioactive functional ingredients from
      marine bioresources and their by-products are alternative sources for synthetic
      ingredients that can contribute to consumer's well-being, as a part of
      nutraceuticals and functional foods. Marine-derived fungi produce a vast array of
      secondary metabolites including terpenes, steroids, polyketides, peptides,
      alkaloids, and polysaccharides. These secondary metabolites serve many
      biopharmaceutical purposes. This chapter discusses about marine fungi-derived
      terpenoids and presents an overview of their beneficial health effects.

PMID- 22361203
TI  - Antimetastasis effect of anthraquinones from marine fungus, Microsporum sp.
AB  - This chapter discusses about obtaining natural products which have anticancer
      metastasis activities from selected marine-derived fungus (Microsporum sp.) and
      investigates their biological activities such as cytotoxicity on viability cell
      lines, anticancer cell migration and invasion, protease inhibition, and
      expression of matrix metalloproteinase (MMP-2 and -9). Moreover, the correlative
      mechanisms behind these activities were studied.

PMID- 22361204
TI  - Application of marine microbial enzymes in the food and pharmaceutical
      industries.
AB  - Over billions of years, the ocean is regarded as the origin of life on Earth, and
      the ocean includes the largest habitats hosting the most life forms. Competition
      among microorganisms for space and nutrients in the marine environment is a
      powerful selective force, which has led to the evolution. The evolution prompts
      the marine microorganisms to generate multifarious enzyme systems to adapt to the
      complicated marine environments. Therefore, marine microbial enzymes can offer
      novel biocatalysts with extraordinary properties. This review deals with the
      research and development work done on the occurrence and bioprocessing of marine
      microbial enzymes.

PMID- 22361205
TI  - Enzymatic properties of starfish phospholipase A2 and its application.
AB  - Industrial phospholipase A2 (PLA2) mainly produced from porcine pancreas is used
      for production of lysolecithin which is well known as an excellent natural
      emulsifier for food, cosmetic, and pharmaceutical industries. Since the outbreak
      of bovine spongiform encephalopathy (BSE) or religious tradition, it is hoped
      that the new sources of PLA2, as well as other enzymes and proteins, will be
      developed instead of mammal. From these backgrounds, we studied for PLA2 from
      marine organisms and found that starfish Asterina pectinifera PLA2 possesses
      extremely high activity and characteristic polar-group specificity comparing with
      commercially available PLA2 from porcine pancreas. Therefore, it was suggested
      that the starfish A. pectinifera would be a potential source of PLA2, and the
      PLA2 can be utilized as alternative enzyme of mammalian PLA2.

PMID- 22361206
TI  - Applications of marine nutraceuticals in dairy products.
AB  - The concept of nutraceutical has been derived by coining the terms "nutrition"
      and "pharmaceutical". In this context, active substances with pharmaceutical
      properties are delivered to the humans through food-based approaches to prevent
      or treat certain disease conditions. Since the natural sources are recognized as
      safe for human consumption, the active substances produced in the diverse group
      of marine organisms have a wide role in the nutraceutical industry. These marine
      derived active ingredients include certain polysaccharides, polyphenols,
      bioactive peptides, polyunsaturated fatty acids, and carotenoids which are known
      to have anticancer, anti-inflammatory, antioxidant, antiobese,
      hypocholesteroleic, antimicrobial, prebiotic, and probiotic activity enabling
      them to be applied as nutraceuticals. As the dairy products are widely accepted
      by the consumers, the delivering of nutraceuticals through dairy products have
      received a greater attention of the dairy industry. Since the incorporation of
      marine-derived active ingredients into the dairy products have caused minimal
      changes in the physico-chemical properties of the final product, marine-derived
      substances have been widely applied and have the potential to be applied as
      nutraceuticals in the dairy industry.

PMID- 22361207
TI  - Upgrading of sea by-products: potential nutraceutical applications.
AB  - Since many years, numerous kinds of processes based on enzymatic hydrolysis at
      various pH, involving added plant or bacterial enzymes after inactivation by
      heating of endogenous enzymes present in the raw material or, alternatively,
      based on the action of endogenous enzymes, have contributed to the degradation of
      marine by-product proteins in order to produce fractions exerting biological
      activities. Peptides obtained by enzymatic hydrolysis of fish proteins exhibit
      not only nutritional but also biological properties of dietary uses, or even
      therapeutic potential. In this review, we have focused on the different enzymatic
      processes able to generate bioactive peptides from marine by-products and
      exerting high potential in nutraceutical applications to fight against important
      public health issues like obesity, stress, hypertension, and migraine. Beyond the
      nutraceutical and pharmaceutical aspects, this way of valorization is also
      included in the necessary development of by-product fishing industries for
      economic and ecological reasons in the worldwide context of marine resources
      depletion.

PMID- 22361208
TI  - Utilization of seafood processing by-products: medicinal applications.
AB  - Large amount of underutilized by-products are generated from the seafood
      processing plants annually. Consequently, researches have been initiated to
      investigate those discarded materials and have identified a number of bioactive
      compounds including bioactive peptides, collagen and gelatin, oligosaccharides,
      fatty acids, enzymes, calcium, water-soluble minerals, and biopolymers. Bioactive
      peptides derived from fish by-products have shown various biological activities
      including antihypertensive and antioxidant activities and hence may be a
      potential material for biomedical and food industries. Collagen and gelatin are
      currently used in diverse fields including food, cosmetic, and biomedical
      industries. Other than that, they are promising drug carriers for the treatment
      of cancer. Many studies have reported that chitin, chitosan, and their
      derivatives possess biologically active polysaccharides and hence they are
      potential agents for many applications. Further, those compounds have also showed
      potential activities such as antioxidant, antibacterial, antiviral,
      antihypertensive, anticancer, etc. Hence, seafood by-products are valuable
      natural resources that show range of functionalities and hence potential
      materials for biomedical and nutraceutical industries.

PMID- 22361210
TI  - Examining variation in depressive symptoms over the life course: a latent class
      analysis.
AB  - BACKGROUND: Older adults have the lowest prevalence and incidence of major
      depressive disorder, although it has been hypothesized that this finding is due
      in part to differences in expression of psychopathology in later life. The aim of
      this study was to examine variation in depressive symptomatology in the general
      population across the lifespan. METHOD: Data came from three sites of the
      Epidemiologic Catchment Area (ECA) Project (n=10 529). Depressive symptoms during
      the past 6 months were assessed using the Diagnostic Interview Schedule (DIS).
      Latent class analysis (LCA) was used to identify homogeneous groups of depressive
      symptomatology based on 16 individual symptoms, and to examine variation in the
      prevalence and composition of depression classes across age groups. RESULTS: The
      DIS symptoms fit a four-class model composed of non-depressed (83.2%), mild
      depression (11.6%), severe depression (1.9%), and despondent (3.2%) groups.
      Relative to the non-depressed class, older age was inversely associated with
      being in the mild or severe depression class. The profile of the latent classes
      was similar across age groups with the exception of the despondent class, which
      was not well differentiated among the youngest adults and was not inversely
      associated with age. CONCLUSIONS: The symptom profiles of depression are similar
      across age with the exception of the despondent class, which is more
      differentiated from severe depression among older adults. The findings
      demonstrate the benefit of examining individual symptoms rather than broad
      symptom groups for understanding the natural history of depression over the
      lifespan.

PMID- 22361211
TI  - The cost-effectiveness of tailored, postal feedback on general practitioners'
      prescribing of pharmacotherapies for alcohol dependence.
AB  - AIMS: The aims of this study were to conduct a randomised controlled trial to
      evaluate the cost-effectiveness of tailored, postal feedback on general
      practitioners' (GPs) prescribing of acamprosate and naltrexone for alcohol
      dependence relative to current practice and its impact on alcohol dependence
      morbidity. METHODS: Rural communities in New South Wales, Australia, were
      randomised into experimental (N=10) and control (N=10) communities. Tailored
      feedback on their prescribing of alcohol pharmacotherapies was mailed to GPs from
      the experimental communities (N=115). Segmented regression analysis was used to
      examine within and between group changes in prescribing and alcohol dependence
      hospitalisation rates compared to the control communities. Incremental cost
      effectiveness ratios (ICERs) were estimated per additional prescription of
      pharmacotherapies and per alcohol dependence hospitalisation(s) averted. RESULTS:
      Post-intervention changes, relative to the control communities, in GPs'
      prescribing rate trends in the experimental communities significantly increased
      for acamprosate (beta=0.24, 95% CI: 0.13-0.35, p<0.001), and significantly
      decreased for naltrexone (beta = -0.12, 95% CI: -0.17 to -0.06) per quarter.
      Quarterly hospitalisation trend rates for alcohol dependence, as principal
      diagnosis, significantly decreased (beta=-0.07, 95% CI: -0.13 to -0.01, p<0.05),
      compared to control communities. The median ICER per quarterly hospitalisation(s)
      averted due to intervention was dominant (dominant--$12,750). CONCLUSION: Postal,
      tailored feedback to GPs on their prescribing of acamprosate and naltrexone for
      alcohol dependence was a cost-effective intervention, in rural communities of
      NSW, to increase the overall prescribing of pharmacotherapies with a plausible
      effect on incidence reduction of hospitalisations for alcohol dependence as
      principal diagnosis.

PMID- 22361212
TI  - Trends in U.S., past-year marijuana use from 1985 to 2009: an age-period-cohort
      analysis.
AB  - BACKGROUND: We present a formal age-period-cohort analysis to examine if the
      recent increase in past-year marijuana use among the young is specific to the
      younger generation or if, instead, it is part of a general increase present
      across cohorts of all ages. This is the first age-period-cohort analysis of past
      year marijuana use that includes adult trends from 2001 to 09. METHODS: Data come
      from the National Survey on Drug Use and Health, a series of annual, nationally
      representative, cross-sectional surveys of the U.S. civilian, non
      institutionalized population. The analysis focuses on the 25 year time span from
      1985 to 2009 and uses the recently developed 'intrinsic estimator' algorithm to
      estimate independent effects of age, period, and cohort. RESULTS: The recent
      increase in past-year marijuana use is not unique to the youngest birth cohorts.
      An independent, positive influence of cohort membership on past-year marijuana
      use, net of historical period and age effects, is smaller for today's youngest
      cohorts than it was for the cohorts that came immediately before, and, in fact,
      is at its lowest level in three decades. The recent increase in marijuana use
      among the young is more consistent with a historical period effect that has acted
      across all cohorts. Period and cohort trends differ substantially for Hispanics.
      CONCLUSIONS: The major forces that drive trends in past-year marijuana use are
      moving away from cohort-specific factors and toward broad-based influences that
      affect cohorts of all ages. Strategic public health and policy efforts aimed at
      addressing the recent increase in past-year marijuana use should do the same.

PMID- 22361213
TI  - Molecular phylogeny of Old World swifts (Aves: Apodiformes, Apodidae, Apus and
      Tachymarptis) based on mitochondrial and nuclear markers.
AB  - We provide a molecular phylogeny for Old World swifts of genera Apus and
      Tachymarptis (tribe Apodini) based on a taxon-complete sampling at the species
      level. Phylogenetic reconstructions were based on two mitochondrial (cytochrome
      b, 12S rRNA) and three nuclear markers (introns of fibrinogen and glyceraldehyde
      3-phosphate dehydrogenase plus anonymous marker 12884) while the myoglobin intron
      2 did not show any intergeneric variation or phylogenetic signal among the target
      taxa at all. In contrast to previous hypotheses, the two genera Apus and
      Tachymarptis were shown as reciprocally monophyletic in all reconstructions. Apus
      was consistently divided into three major clades: (1) East Asian clade of A.
      pacificus and A. acuticauda, (2) African-Asian clade of A. caffer, A. batesi, A.
      horus, A. affinis and A. nipalensis, (3) African-Palearctic clade of eight
      currently accepted species among which sequences of A. apus and A. pallidus
      clustered in a terminal crown clade. Phylogenetic signal of all four nuclear
      markers was extremely shallow within and among species of tribe Apodini and even
      among genera, such that intra- and intergeneric relationships of Apus,
      Tachymarptis and Cypsiurus were poorly resolved by nuclear data alone. Four
      species, A. pacificus, A. barbatus, A. affinis and A. caffer were consistently
      found to be paraphyletic with respect to their closest relatives and possible
      taxonomic consequences are discussed without giving particular recommendations
      due to limitations of sampling. Incomplete mitochondrial lineage sorting with
      cytochrome-b haplotypes shared among species and across large geographic
      distances was observed in two species pairs: A. affinis/A. nipalensis and A.
      apus/A. pallidus. Mitochondrial introgression caused by extant or past gene flow
      was ruled out as an explanation for the low interspecific differentiation in
      these two cases because all nuclear markers appeared to be highly unsorted among
      Apus species, too. Apparently, the two extant species pairs originated from very
      recent dispersal and/or speciation events. The currently accepted superspecies
      classification within Apus was not supported by our results.

PMID- 22361214
TI  - The highly conserved spermatophyte cell wall DUF642 protein family: phylogeny and
      first evidence of interaction with cell wall polysaccharides in vitro.
AB  - The evolution of spermatophyte plants involved fundamental changes in cell wall
      structure and function which resulted from diversification of carbohydrates and
      proteins. Cell wall proteomic analyses identified a novel family of proteins of
      yet unknown function, the DUF642 (Domain of Unknown Function 642) proteins. To
      investigate the evolution of the DUF642 gene family, 154 gene sequences from 24
      plant species were analyzed, and phylogenetic inferences were conducted using the
      Maximum Likelihood and Bayesian Inference methods. Orthologous genes were
      detected in spermatophyte species and absent in non-seed known plant genomes.
      Protein sequences shared conserved motifs that defined the signature of the
      family. Distribution of conserved motifs indicated an ancestral intragenic
      duplication event. Gene phylogeny documented paleoduplication events originating
      three or four clades, depending on root position. When based on mid-point
      rooting, it retrieved four monophyletic clades: A, B, C, and D. A
      glycosylphosphatidylinositol (GPI)-anchor site and one or two galactose-binding
      domains-like (GBDLs) could be predicted for some DUF642 proteins. The B, C, and D
      clades grouped the predicted GPI-anchored proteins. First evidence of in vitro
      interaction of a DUF642 protein with a cell wall polysaccharide fraction is
      provided. A competition assay with cellulose prevented this interaction. The
      degree of diversification and the conservation of the family suggested that
      DUF642 proteins are key components in seed plant evolution.

PMID- 22361215
TI  - The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial
      protrusions.
AB  - Neurite formation is a seminal event in the early development of neurons.
      However, little is known about the mechanisms by which neurons form neurites. F
      BAR proteins function in sensing and inducing membrane curvature. Cdc42
      interacting protein 4 (CIP4), a member of the F-BAR family, regulates endocytosis
      in a variety of cell types. However, there is little data on how CIP4 functions
      in neurons. Here we show that CIP4 plays a novel role in neuronal development by
      inhibiting neurite formation. Remarkably, CIP4 exerts this effect not through
      endocytosis, but by producing lamellipodial protrusions. In primary cortical
      neurons CIP4 is concentrated specifically at the tips of extending lamellipodia
      and filopodia, instead of endosomes as in other cell types. Overexpression of
      CIP4 results in lamellipodial protrusions around the cell body, subsequently
      delaying neurite formation and enlarging growth cones. These effects depend on
      the F-BAR and SH3 domains of CIP4 and on its ability to multimerize. Conversely,
      cortical neurons from CIP4-null mice initiate neurites twice as fast as controls.
      This is the first study to demonstrate that an F-BAR protein functions
      differently in neuronal versus nonneuronal cells and induces lamellipodial
      protrusions instead of invaginations or filopodia-like structures.

PMID- 22361216
TI  - Effect of chronic exposure to pendimethalin on the susceptibility of rainbow
      trout, Oncorhynchus mykiss L., to viral hemorrhagic septicemia virus (VHSV).
AB  - In this study, the in vivo effects of chronic pollution by the active substance
      (AS) pendimethalin, a dinitroaniline herbicide, on the susceptibility of rainbow
      trout, Oncorhynchus mykiss L., to an experimental challenge with viral
      hemorrhagic septicemia virus (VHSV) were assessed. After four weeks of exposure
      to fresh water (C group) or 500 ng L(-1) of AS (P500 group), the fish were
      challenged by immersion in water containing 10(4) TCID(50) mL(-1) of VHSV. While
      exposure to pendimethalin was maintained throughout the experiment, mortalities
      were recorded during the 40 days post-infection (dpi) and organs were collected
      from dead fish for virological examination. At the end of the experiment, anti
      VHSV antibodies and the classical pathway of complement activity were assessed in
      trout plasma. Exposure to pendimethalin significantly affected the distribution
      of cumulative mortality accelerating death in fish infected by VHSV.
      Pendimethalin appeared to decrease the Mean Time to Death (MTD) after virus
      treatment from 14.9 days (C-VHSV) to 10.2 days (P500-VHSV). Nevertheless, by the
      end of the experiment, differences in cumulative mortality were no longer
      observed between the two groups, which had reached the same stage (50 percent).
      Furthermore, a higher concentration of the virus was recovered from the pools of
      organs from the P500-VHSV group than the C-VHSV group. Moreover, at 40 dpi,
      although no significant difference was observed in the immune response between
      the two groups, more fish in the P500-VHSV group had set up an immune response by
      secreting antibodies than in the control viral group (C-VSHV).

PMID- 22361217
TI  - In silico assessment of the potential allergenicity of transgenes used for the
      development of GM food crops.
AB  - Genetically modified (GM) crops require allergenicity and toxicity assessment of
      the novel protein(s) to ensure complete safety to the consumers. These
      assessments are performed in accordance with the guidelines proposed by Codex
      (2003) and ICMR (2008). The guidelines recommend sequence homology analysis as a
      preliminary step towards allergenicity prediction, later in vitro experiments may
      be performed to confirm allergenicity. In the present study, an in silico
      approach is employed to evaluate the allergenic potential of six transgenes
      routinely used for the development of GM food crops. Among the genes studied,
      manganese superoxide dismutase (MnSOD) and osmotin shares greater than 90%
      identity with Hev b 10 and Cap a 1w, respectively. Chitinase shares greater than
      70% identity with allergens namely Pers a 1 and Hev b 11, and fungal chitinase
      showed significant IgE binding with 7 of 75 patients' sera positive to different
      food extracts. Glucanases (alfalfa, wheat) and glycine betaine aldehyde
      dehydrogenase gene share 50% homology with allergens like - Ole e 9, Cla h 10 and
      Alt a 10. The results demonstrate the allergenic potential of six genes and can
      serve as a guide for selection of transgenes to develop GM crops.

PMID- 22361218
TI  - Prognostic score for second-line chemotherapy of advanced non-small-cell lung
      cancer: external validation in a phase III trial comparing vinflunine with
      docetaxel.
AB  - A prognostic index for second-line chemotherapy of NSCLC was previously
      developed, based on individual patient data (IPD) of nine randomized trials. In
      order to validate the prognostic score in an external dataset, we analysed IPD of
      a non-inferiority phase III trial comparing vinflunine vs. docetaxel in second
      line treatment of advanced NSCLC. Primary endpoint of this analysis was overall
      survival (OS). The following variables were considered for survival analysis and
      score calculation: gender, performance status, stage of disease, tumour
      histology, type of first-line treatment, response to first-line treatment. Cox
      model, stratified by treatment arm, was used for multivariate analysis.
      Individual prognostic scores were derived, and patients were divided into 3
      categories: <5 (best), 5-9 (intermediate), >9 (worst). All 551 patients enrolled
      in the trial had complete information for the calculation of prognostic score.
      Median OS in the whole group was 6.9 months, with similar efficacy in the two
      treatment arms. Median OS was 12.9, 6.9 and 3.8 months in the best, intermediate
      and worst category, respectively. Cox model showed a significant effect comparing
      intermediate vs. best category (Hazard Ratio 1.79, 95%CI 1.31-2.47, p=0.0003) and
      comparing worst vs. best category (Hazard Ratio 3.25, 95%CI 2.18-4.83, p<0.0001).
      The C-index of the model was high (0.926), indicating a good discrimination
      according to the proposed three risk categories. Prognostic ability of our score
      for candidates to second-line treatment in advanced NSCLC was successfully
      validated, allowing the identification of subgroups of patients with more vs.
      less favourable outcome. Prognostic score could be useful in daily decision
      making in clinical practise, because a better understanding of factors
      conditioning life expectancy of patients could greatly help a careful evaluation
      of risks and benefits associated with therapeutic decisions.

PMID- 22361219
TI  - A novel duplex real-time PCR for HPIV-4 detects co-circulation of both viral
      subtypes among ill children during 2008.
AB  - The two subtypes of the human parainfluenzavirus type 4 (HPIV-4) are rarely
      sought in testing for acute respiratory illness (ARI) and this may be confounding
      our understanding of its role. This study presents a novel duplex real-time RT
      PCR assay targeting the P gene that can detect and differentiate the two subtypes
      in a single reaction. Subtype-specific synthetic RNA positive controls were
      prepared and used to determine an analytical sensitivity of 10 copies per
      reaction with an 8log(10) dynamic range. The assays were validated using 1140
      clinical specimens mostly nasopharyngeal aspirates collected from children during
      2008. These included specimens previously determined to be positive for all
      commonly considered respiratory viruses. The novel assay did not cross-reaction
      with any other virus. Fourteen HPIV-4 positives, ten detected in the absence of
      any co-detections (four with rhinovirus), were identified in 2008 and their
      subtype confirmed by conventional RT-PCR and sequencing of P gene fragments. Most
      detections were in children two years of age or younger. Our assay proved
      suitably sensitive and specific for inclusion in future studies seeking to better
      understand the role HPIV-4 and other respiratory viruses in children with ARI.

PMID- 22361220
TI  - Diabetes mellitus and growth in children and adolescents.

PMID- 22361222
TI  - Characterization and specificity of the linear epitope of the enterovirus 71 VP2
      protein.
AB  - BACKGROUND: Enterovirus 71 (EV71) has emerged as a major causative agent of hand,
      foot and mouth disease in the Asia-Pacific region over the last decade. Hand,
      foot and mouth disease can be caused by different etiological agents from the
      enterovirus family, mainly EV71 and coxsackieviruses, which are genetically
      closely related. Nevertheless, infection with EV71 may occasionally lead to high
      fever, neurologic complications and the emergence of a rapidly fatal syndrome of
      pulmonary edema associated with brainstem encephalitis. The rapid progression and
      high mortality of severe EV71 infection has highlighted the need for EV71
      specific diagnostic and therapeutic tools. Monoclonal antibodies are urgently
      needed to specifically detect EV71 antigens from patient specimens early in the
      infection process. Furthermore, the elucidation of viral epitopes will contribute
      to the development of targeted therapeutics and vaccines. RESULTS: We have
      identified the monoclonal antibody 7C7 from a screen of hybridoma cells derived
      from mice immunized with the EV71-B5 strain. The linear epitope of 7C7 was mapped
      to amino acids 142-146 (EDSHP) of the VP2 capsid protein and was characterized in
      detail. Mutational analysis of the epitope showed that the aspartic acid to
      asparagine mutation of the EV71 subgenogroup A (BrCr strain) did not interfere
      with antibody recognition. In contrast, the serine to threonine mutation at
      position 144 of VP2, present in recently emerged EV71-C4 China strains, abolished
      antigenicity. Mice injected with this virus strain did not produce any antibodies
      against the VP2 protein. Immunofluorescence and Western blotting confirmed that
      7C7 specifically recognized EV71 subgenogroups and did not cross-react to
      Coxsackieviruses 4, 6, 10, and 16. 7C7 was successfully used as a detection
      antibody in an antigen-capture ELISA assay. CONCLUSIONS: Detailed mapping showed
      that the VP2 protein of Enterovirus 71 contains a single, linear, non
      neutralizing epitope, spanning amino acids 142-146 which are located in the VP2
      protein's E-F loop. The S/T(144) mutation in this epitope confers a loss of VP2
      antigenicity to some newly emerged EV71-C4 strains from China. The corresponding
      monoclonal antibody 7C7 was used successfully in an AC-ELISA and did not cross
      react to coxsackieviruses 4, 6, 10, and 16 in immunofluorescence assay and
      Western blots. 7C7 is the first monoclonal antibody described, that can
      differentiate Coxsackievirus 16 from Enterovirus 71.

PMID- 22361223
TI  - Comparative seroepidemiology of diphtheria in six European countries and Israel.
AB  - Serological surveys for diphtheria were conducted in six European countries
      including Czech Republic, Hungary, Ireland, Latvia, Luxembourg, Slovakia and one
      country outside Europe, Israel. For each country, a nationally representative
      population sample was collected across the entire age range and was tested for
      antibodies to diphtheria toxin. Although each national laboratory used its
      preferred assay, the results were all standardized to those of the in vitro
      neutralization test and expressed in international units (IU) which allowed
      comparative analyses to be performed. The results showed that increasing age is
      related to a gradual increase in seronegative subjects (<0.01 IU/ml of diphtheria
      antitoxin antibodies). This may reflect waning immunity following childhood
      vaccination without repeated booster vaccinations in adults. Differences in
      seronegativity were also found according to gender. In subjects aged 1-19 years,
      geometric mean titres of antitoxin are clearly related to the different
      vaccination schedules used in the participating countries. Although clinical
      disease remains rare, the susceptibility to diphtheria observed in these
      serosurveys highlights the importance of strengthened surveillance.

PMID- 22361221
TI  - Demographic and clinical correlates of diabetes-related quality of life among
      youth with type 1 diabetes.
AB  - OBJECTIVES: To evaluate the reliability and cluster structure of the Pediatric
      Quality of Life Inventory Type 1 Diabetes Module 3.0 (PedsQL-T1DM) and associated
      subscales and to explore the associations between PedsQL-T1DM total score and
      demographic and clinical characteristics and clinical indicators among a large
      racially/ethnically diverse cohort of youth with type 1 diabetes. STUDY DESIGN:
      Principal components analysis was conducted on responses from the PedsQL-T1DM
      child self-report forms completed by SEARCH for Diabetes in Youth study
      participants aged >= 5 years. Multivariate linear regression models were fit to
      examine the associations among PedsQL-T1DM total score, demographic and clinical
      characteristics, and clinical indicators. RESULTS: The sample comprised 2602
      youth with a mean age of 13.6 +/- 4.1 years and a mean T1DM duration of 62.1 +/-
      47.0 months. Principal components analysis did not support the 5 existing PedsQL
      T1DM subscales. In multivariate analyses, the PedsQL-T1DM total score was
      negatively and significantly associated with younger age (5-7 years), female sex,
      receiving insulin by injection (vs pump), having parents without a college
      degree, Medicaid/Medicare insurance, and having a comorbid medical condition.
      Youth with poor glycemic control based on their age-specific hemoglobin A1c
      target values and those with depressive symptoms had significantly lower PedsQL
      T1DM scores than their counterparts with good control and no or limited
      depressive symptoms. CONCLUSION: This study has identified sociodemographic and
      clinical characteristics of youth with T1DM more likely to experience poor
      diabetes-specific quality of life. The association of lower PedsQL-T1DM scores
      with depressive symptoms and poor glycemic control is especially concerning and
      may be the focus of future interventions and studies.

PMID- 22361225
TI  - Comment on: Ischaemic manifestations in giant cell arteritis are associated with
      area level socio-economic deprivation, but not cardiovascular risk factors.

PMID- 22361226
TI  - Hyperferritinaemia and macrophage activation in a patient with interstitial lung
      disease with clinically amyopathic DM.

PMID- 22361227
TI  - Pneumothorax as a first manifestation of SS.

PMID- 22361228
TI  - Complement C3 gene polymorphism in renal transplantation (an Iranian experience).
AB  - The C3 component of complement has different roles in kidney disease and its
      local production in donor kidney may affect allograft function and rejection
      after organ transplantation. A single base substitution in c3 gene (rs2230199),
      defines two common allelic variants with different mobility on gel
      electrophoresis: S (Slow) and F (Fast). In order to evaluate the effect of this
      polymorphism on acute renal allograft rejection, one hundred samples of donor and
      recipients were collected and genotyping was done by PCR-RFLP method. The allelic
      frequencies were: C3S=0.791, C3F=0.209. There was no significant association
      between recipient's genotype and acute rejection (p value<0.05). No correlation
      between donor genotype and acute rejection was also present. Patients were
      divided into four groups, according to the recipient and donor genotypes: SS
      recipients and FS or FF donor, SS recipient and donor, FF or FS recipient and SS
      donor and FS or FF recipient and donor. There was no significant difference in
      rate of acute rejection between groups. Although the results didn't find any
      association between C3 complement polymorphisms and acute allograft rejection,
      there was no acute rejection in FS or FF donors and SS recipient group.

PMID- 22361230
TI  - Low sodium diet.

PMID- 22361231
TI  - Linking public health agencies and hospitals for improved emergency preparedness:
      North Carolina's public health epidemiologist program.
AB  - BACKGROUND: In 2003, 11 public health epidemiologists were placed in North
      Carolina's largest hospitals to enhance communication between public health
      agencies and healthcare systems for improved emergency preparedness. We describe
      the specific services public health epidemiologists provide to local health
      departments, the North Carolina Division of Public Health, and the hospitals in
      which they are based, and assess the value of these services to stakeholders.
      METHODS: We surveyed and/or interviewed public health epidemiologists,
      communicable disease nurses based at local health departments, North Carolina
      Division of Public Health staff, and public health epidemiologists' hospital
      supervisors to 1) elicit the services provided by public health epidemiologists
      in daily practice and during emergencies and 2) examine the value of these
      services. Interviews were transcribed and imported into ATLAS.ti for coding and
      analysis. Descriptive analyses were performed on quantitative survey data.
      RESULTS: Public health epidemiologists conduct syndromic surveillance of
      community-acquired infections and potential bioterrorism events, assist local
      health departments and the North Carolina Division of Public Health with public
      health investigations, educate clinicians on diseases of public health
      importance, and enhance communication between hospitals and public health
      agencies. Stakeholders place on a high value on the unique services provided by
      public health epidemiologists. CONCLUSIONS: Public health epidemiologists
      effectively link public health agencies and hospitals to enhance syndromic
      surveillance, communicable disease management, and public health emergency
      preparedness and response. This comprehensive description of the program and its
      value to stakeholders, both in routine daily practice and in responding to a
      major public health emergency, can inform other states that may wish to establish
      a similar program as part of their larger public health emergency preparedness
      and response system.

PMID- 22361232
TI  - Contributions of central and systemic inflammation to the pathophysiology of
      Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD) represents a complex interaction between the
      inherent vulnerability of the nigrostriatal dopaminergic system, a possible
      genetic predisposition, and exposure to environmental toxins including
      inflammatory triggers. Evidence now suggests that chronic neuroinflammation is
      consistently associated with the pathophysiology of PD. Activation of microglia
      and increased levels of pro-inflammatory mediators such as TNF-alpha, IL-1beta
      and IL-6, reactive oxygen species and eicosanoids has been reported after post
      mortem analysis of the substantia nigra from PD patients and in animal models of
      PD. It is hypothesised that chronically activated microglia secrete high levels
      of pro-inflammatory mediators which damage neurons and further activate
      microglia, resulting in a feed forward cycle promoting further inflammation and
      neurodegeneration. Moreover, nigrostriatal dopaminergic neurons are more
      vulnerable to pro-inflammatory and oxidative mediators than other cell types
      because of their low intracellular glutathione concentration. Systemic
      inflammation has also been suggested to contribute to neurodegeneration in PD, as
      lymphocyte infiltration has been observed in brains of PD patients and in animal
      models of PD, substantiating the current theory of a fundamental role of
      inflammation in neurodegeneration. We will examine the current evidence in the
      literature which offers insight into the premise that both central and systemic
      inflammation may contribute to neurodegeneration in PD. We will discuss the
      emerging possibility of the use of diagnostic tools such as imaging technologies
      for PD patients. Finally, we will present the immunomodulatory therapeutic
      strategies that are now under investigation and in clinical trials as potential
      neuroprotective drugs for PD.

PMID- 22361233
TI  - Neuritic growth impairment and cell death by unconjugated bilirubin is mediated
      by NO and glutamate, modulated by microglia, and prevented by
      glycoursodeoxycholic acid and interleukin-10.
AB  - Neuronal oxidative damage and cell death by unconjugated bilirubin (UCB) showed
      to be mediated by overstimulation of glutamate receptors and nitric oxide (NO)
      production, which was abrogated by the bile acid glycoursodeoxycholic acid
      (GUDCA). Microglia, a crucial mediator of CNS inflammation, evidenced to react to
      UCB by releasing glutamate and NO before becoming senescent. Our studies
      demonstrated that neurite outgrowth deficits are produced in neurons exposed to
      UCB and that conditioned media from these UCB-treated neurons further stimulate
      NO production by microglia. Nevertheless, microglia protective and/or harmful
      effects in neonatal jaundice are poorly understood, or unrecognized. Here, we
      investigated the role of microglia, glutamate and NO in the impairment of neurite
      sprouting by UCB. Therapeutic potential of the anti-inflammatory cytokine
      interleukin (IL)-10 and GUDCA was also evaluated. By using MK-801 (a NMDA
      glutamate-subtype receptor antagonist) and L-NAME (a non-specific NO synthase
      inhibitor) we found that glutamate and NO are determinants in the early and
      enduring deficits in neurite extension and ramification induced by UCB. Both
      GUDCA and IL-10 prevented these effects and decreased the production of glutamate
      and NO. Only GUDCA was able to counteract neuronal death and synaptic changes.
      Data from organotypic-cultured hippocampal slices, depleted or non-depleted in
      microglia, supported that microglia participate in glutamate homeostasis and
      contribute to NO production and cell demise, which were again abrogated by GUDCA.
      Collectively our data suggest that microglia is a key player in UCB-induced
      neurotoxicity and that GUDCA might be a valuable preventive therapy in neonates
      at risk of UCB encephalopathy.

PMID- 22361234
TI  - A multiplex (m)RNA-profiling system for the forensic identification of body
      fluids and contact traces.
AB  - In current forensic practice, information about the possible biological origin of
      forensic traces is mostly determined using protein-based presumptive testing.
      Recently, messenger RNA-profiling has emerged as an alternative strategy to
      examine the biological origin. Here we describe the development of a single
      multiplex mRNA-based system for the discrimination of the most common forensic
      body fluids as well as skin cells. A DNA/RNA co-isolation protocol was
      established that results in DNA yields equivalent to our standard in-house
      validated DNA extraction procedure which uses silica-based columns. An endpoint
      RT-PCR assay was developed that simultaneously amplifies 19 (m)RNA markers. This
      multiplex assay analyses three housekeeping, three blood, two saliva, two semen,
      two menstrual secretion, two vaginal mucosa, three general mucosa and two skin
      markers. The assay has good sensitivity as full RNA profiles for blood, semen and
      saliva were obtained when using >=0.05 MUL body fluid starting material whereas
      full DNA profiles were obtained with >=0.1 MUL. We investigated the specificity
      of the markers by analysing 15 different sets of each type of body fluid and skin
      with each set consisting of 8 individuals. Since skin markers have not been
      incorporated in multiplex endpoint PCR assays previously, we analysed these
      markers in more detail. Interestingly, both skin markers gave a positive result
      in samplings of the hands, feet, back and lips but negative in tongue samplings.
      Positive identification (regarding both DNA- and RNA-profiling) was obtained for
      specimens stored for many years, e.g. blood (28 years-old), semen (28 years-old),
      saliva (6 years-old), skin (10 years-old) and menstrual secretion (4 years-old).
      The described approach of combined DNA- and RNA-profiling of body fluids and
      contact traces assists in the interpretation of forensic stains by providing
      information about not only the donor(s) that contributed to the stain but also by
      indicating which cell types are present.

PMID- 22361235
TI  - Characterization of protein glycosylation in Francisella tularensis subsp.
      holarctica: identification of a novel glycosylated lipoprotein required for
      virulence.
AB  - FTH_0069 is a previously uncharacterized strongly immunoreactive protein that has
      been proposed to be a novel virulence factor in Francisella tularensis. Here, the
      glycan structure modifying two C-terminal peptides of FTH_0069 was identified
      utilizing high resolution, high mass accuracy mass spectrometry, combined with in
      source CID tandem MS experiments. The glycan observed at m/z 1156 was determined
      to be a hexasaccharide, consisting of two hexoses, three N-acetylhexosamines, and
      an unknown monosaccharide containing a phosphate group. The monosaccharide
      sequence of the glycan is tentatively proposed as X-P-HexNAc-HexNAc-Hex-Hex
      HexNAc, where X denotes the unknown monosaccharide. The glycan is identical to
      that of DsbA glycoprotein, as well as to one of the multiple glycan structures
      modifying the type IV pilin PilA, suggesting a common biosynthetic pathway for
      the protein modification. Here, we demonstrate that the glycosylation of
      FTH_0069, DsbA, and PilA was affected in an isogenic mutant with a disrupted
      wbtDEF gene cluster encoding O-antigen synthesis and in a mutant with a deleted
      pglA gene encoding pilin oligosaccharyltransferase PglA. Based on our findings,
      we propose that PglA is involved in both pilin and general F. tularensis protein
      glycosylation, and we further suggest an inter-relationship between the O-antigen
      and the glycan synthesis in the early steps in their biosynthetic pathways.

PMID- 22361236
TI  - Targeted proteomics of the eicosanoid biosynthetic pathway completes an
      integrated genomics-proteomics-metabolomics picture of cellular metabolism.
AB  - Eicosanoids constitute a diverse class of bioactive lipid mediators that are
      produced from arachidonic acid and play critical roles in cell signaling and
      inflammatory aspects of numerous diseases. We have previously quantified
      eicosanoid metabolite production in RAW264.7 macrophage cells in response to Toll
      like receptor 4 signaling and analyzed the levels of transcripts coding for the
      enzymes involved in the eicosanoid metabolite biosynthetic pathways. We now
      report the quantification of changes in protein levels under similar experimental
      conditions in RAW264.7 macrophages by multiple reaction monitoring mass
      spectrometry, an accurate targeted protein quantification method. The data
      complete the first fully integrated genomic, proteomic, and metabolomic analysis
      of the eicosanoid biochemical pathway.

PMID- 22361237
TI  - Cartilage and bone changes during development of post-traumatic osteoarthritis in
      selected LGXSM recombinant inbred mice.
AB  - INTRODUCTION: Little evidence is available on the natural course of
      osteoarthritis (OA) development and the genes that protect and predispose
      individuals to it. This study was designed to compare strain-dependent
      development of OA and its association with tissue regeneration in mice. Two
      recombinant inbred lines LGXSM-6 and LGXSM-33 generated from LG/J and SM/J
      intercross were used. Previous studies indicated that LGXSM-6 can regenerate both
      articular cartilage and ear hole punch while LGXSM-33 cannot. METHODS:
      Transection of the medial meniscotibial ligament was performed on 10-week-old
      male mice to induce OA. Cartilage damage was analyzed by histology and bone
      morphology was evaluated using micro-computed tomography (CT). Ear punches were
      performed and evaluated by measurement of residual hole diameter. RESULTS:
      Cartilage analysis showed that LGXSM-33 developed a significantly higher grade of
      OA than LGXSM-6. Bone analysis showed that LGXSM-33 had substantial subchondral
      bone and trabecular bone thickening 8 weeks post-surgery, while LGXSM-6 showed
      bone loss over time. We also confirmed that LGXSM-6 can heal ear tissues
      significantly better than LGXSM-33. CONCLUSIONS: OA was found to be negatively
      correlated with the degree of tissue regeneration. LGXSM-33, a poor healer of ear
      tissues (and articular cartilage), developed more OA compared to LGXSM-6, which
      had better regenerative ability for ear tissues and articular cartilage. The
      phenotypic differences observed here are due to genetic differences further
      suggesting that similar sets of physiological processes and gene variants may
      mediate variation in OA development and tissue regeneration.

PMID- 22361238
TI  - Circulating levels of persistent organic pollutants (POPs) among elderly men and
      women from Sweden: results from the Prospective Investigation of the Vasculature
      in Uppsala Seniors (PIVUS).
AB  - Persistent Organic Pollutants (POPs) are a huge group of chemicals that have been
      linked to various adverse health effects in humans. Large epidemiological studies
      investigating gender differences in levels of POPs in the elderly are limited and
      the results from these are not always consistent. The present study was
      undertaken to examine the background levels of a broad range of POPs in human
      plasma samples among elderly men and women from Sweden and to assess the
      influence of gender. Levels of 23 POPs were determined in plasma samples
      collected during 2001-2004 from 1016 (50.2% women) 70year-old participants from
      the population-based Prospective Study of the Vasculature in Uppsala Seniors
      (PIVUS). Measurements were performed using high resolution gas chromatography
      with high resolution mass spectrometry (HRGC-HRMS) and the POPs studied were 16
      polychlorinated biphenyls (PCBs), five organochlorine (OC) pesticides, one
      dioxin, and one brominated flame retardant. The concentrations of the selected
      POPs were found similar, or comparable, to other studies of non-occupationally
      exposed populations from Sweden and Europe. Differences in levels of POPs between
      men and women were assessed by using Wilcoxon rank-sum (Mann-Whitney) test.
      Significant (p<0.0001) gender differences in levels of specific POPs were
      observed and a number of POP concentrations were found to differ between men and
      women. More specifically, levels of HCB, OCDD, and PCB congeners #74, #105, and
      #118 were found to be higher in women, while the rest of the majority of POPs
      were higher in men.

PMID- 22361239
TI  - Environmental tobacco smoke in designated smoking areas in the hospitality
      industry: exposure measurements, exposure modelling and policy assessment.
AB  - Tobacco control policy has been enacted in many jurisdictions worldwide banning
      smoking in the workplace. In the hospitality sector many businesses such as bars,
      hotels and restaurants have installed designated smoking areas on their premises
      and allowance for such smoking areas has been made in the tobacco control
      legislation of many countries. An investigation was carried out into the level of
      exposure to environmental tobacco smoke (ETS) present in 8 pubs in Ireland which
      included designated smoking areas complying with two different definitions of a
      smoking area set out in Irish legislation. In addition, ETS exposure in a pub
      with a designated smoking area not in compliance with the legislation was also
      investigated. The results of this investigation showed that the two differing
      definitions of a smoking area present in pubs produced similar concentrations of
      benzene within smoking areas (5.1-5.4 MUg/m(3)) but differing concentrations
      within the 'smoke-free' areas (1.42-3.01 MUg/m(3)). Smoking areas in breach of
      legislative definitions were found to produce the highest levels of benzene in
      the smoking area (49.5 MUg/m(3)) and 'smoke-free' area (7.68 MUg/m(3)). 3D
      exposure modelling of hypothetical smoking areas showed that a wide range of ETS
      exposure concentrations were possible in smoking areas with the same floor area
      and same smoking rate but differing height to width and length to width ratios.
      The results of this investigation demonstrate that significant scope for
      improvement of ETS exposure concentrations in pubs and in smoking areas may exist
      by refining and improving the legislative definitions of smoking areas in law.

PMID- 22361240
TI  - The public health threat of phthalate-tainted foodstuffs in Taiwan: the policies
      the government implemented and the lessons we learned.
AB  - A major incident of phthalate-contaminated foodstuffs happened in Taiwan between
      April and July, 2011. Phthalates were deliberately added to foodstuffs as a
      substitute of emulsifier. We describe the course of this incident, government
      response and management of the crisis, and its future implications. Five major
      food categories, including sports drinks, fruit beverages, tea drinks, fruit jam
      or jelly, and health food or supplements in tablet or powder form, were
      contaminated with Di-(2-ethylhexyl)phthalate and/or Di-isononyl phthalate. At
      least 900 different food products were affected. Like the scandal of melamine
      tainted infant formula, this event represents another large deliberate food
      contamination incident. It is important to be reminded that many governments in
      developing countries make rapid economic growth as their first priority, often
      compromising environmental safety and public health. The administration leaders
      need to find a balance between economic expansion and health and environmental
      safety.

PMID- 22361241
TI  - Family communication patterns and teen drivers' attitudes toward driving safety.
AB  - INTRODUCTION: Family communication patterns (FCPs) play an important role in
      reducing the risk-taking behaviors of teens, such as substance use and safer sex.
      However, little is known about the relationship between family communication and
      teen driving safety. METHOD: We analyzed the baseline data from a randomized
      trial that included 163 parent-teen dyads, with teens who would be receiving
      their intermediate driver's license within 3 months. FCPs were divided into four
      types-pluralistic, protective, consensual, and laissez-faire-and were correlated
      with the frequency of parent-teen discussions and teens' driving safety
      attitudes. RESULTS: The ratings on four types of FCPs were distributed quite
      evenly among teens and parents. Parents and teens agreed on their FCP ratings (p
      = .64). In families with communication patterns that were laissez-faire,
      protective, and pluralistic, parents talked to their teens less about safe
      driving than did parents in families with a consensual communication pattern (p <
      .01). Moreover, the frequency of parent-teen communication about safe driving was
      positively associated with teen attitudes toward safe driving (adjusted beta =
      0.35, p = .03). DISCUSSION: Health care providers need to encourage parents,
      particularly those with non-consensual FCPs, to increase frequency of parent-teen
      interactions.

PMID- 22361242
TI  - Breaking the ice: a pre-intervention strategy to engage research participants.

PMID- 22361243
TI  - Induction of ssDNA-binding autoantibody secreting B cell immunity during murine
      malaria infection is a critical part of the protective immune responses.
AB  - Although it has been hypothesized that autoimmune-like phenomena may play a
      critical role in the protective immune responses to both human and animal
      malaria, there are still no evidence-based data to support this view. In this
      study we demonstrate that the majority of anti-single stranded (ss) DNA
      autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and
      that these cells expanded significantly in the spleen of C57BL/6 mice infected
      with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA
      binding autoantibody secreting B cell responses in murine malaria, we conjugated
      generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete
      ssDNA-binding autoreactive B cells in vivo. Our data revealed that 55.5% of mice
      died after DNA-coated nanoparticle-mediated in vivo depletion of ssDNA-specific
      autoreactive B cells and subsequent challenge using PyNL. Adoptive transfer of B
      cells with ssDNA specificity to mice, followed by PyNL infection, caused a later
      appearance and inhibition of parasitemia. The possible mechanism by which the
      ssDNA-binding autoantibody secreting B cells is involved in the protection
      against murine malaria has also been demonstrated.

PMID- 22361244
TI  - Endothelial dysfunction in the pulmonary artery induced by concentrated fine
      particulate matter exposure is associated with local but not systemic
      inflammation.
AB  - Clinical evidence has identified the pulmonary circulation as an important target
      of air pollution. It was previously demonstrated that in vitro exposure to fine
      particulate matter (aerodynamic diameter<=2.5 MUm, PM2.5) induces endothelial
      dysfunction in isolated pulmonary arteries. We aimed to investigate the effects
      of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery
      reactivity and the mechanisms involved. For this, adult Wistar rats were exposed
      to 2 weeks of concentrated Sao Paulo city air PM2.5 at an accumulated daily dose
      of approximately 600 MUg/m3. Pulmonary arteries isolated from PM2.5-exposed
      animals exhibited impaired endothelium-dependent relaxation to acetylcholine
      without significant changes in nitric oxide donor response compared to control
      rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of
      Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of
      endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor
      (TNF)-alpha was enhanced by PM2.5 inhalation in pulmonary artery. There was a
      significant positive correlation between eNOS expression and maximal relaxation
      response (Emax) to acetylcholine. A negative correlation was found between
      vascular TNF-alpha expression and Emax to acetylcholine. Plasma cytokine levels,
      blood cells count and coagulation parameters were similar between control and
      PM2.5-exposed rats. The present findings showed that in vivo daily exposure to
      concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS
      expression on pulmonary arteries associated with local high TNF-alpha level but
      not systemic pro-inflammatory factors. Taken together, the present results
      elucidate the mechanisms underlying the trigger of cardiopulmonary diseases
      induced by urban ambient levels of PM2.5.

PMID- 22361245
TI  - Evaluation of the Vietnamese A6 mortality reporting system: injury as a cause of
      death.
AB  - BACKGROUND: Despite the fact that the A6 mortality reporting system has been
      operating for almost 20 years in Vietnam, there has been no systematic evaluation
      of the system. This study assesses the completeness, sensitivity and positive
      predictive value of the system in relation to injury related mortality. METHODS:
      Evaluation of the A6 system was undertaken in three (geographically distributed)
      provinces in Vietnam. Deaths identified in the A6 system were compared with
      deaths identified by an independent consensus panel to determine the per cent
      completeness of the A6 system. Verbal autopsies (VA) were conducted for all
      identified deaths from the consensus panels, and the sensitivity and positive
      predictive value of the A6 system were assessed using the VAs as the reference.
      RESULTS: 5273 deaths were identified from the A6 system with a further 340 cases
      identified by the independent consensus panel (total n=5613). Injury related
      deaths accounted for 13.6% (n=763) of all deaths with an overall injury mortality
      rate of 55.3 per 100 000 person years. The per cent completeness of the A6 system
      in relation to injury deaths was 93.9% with a sensitivity of 75.4%, specificity
      of 98.4% and positive predictive value of 88.4%. CONCLUSIONS: The A6 mortality
      reporting system is embedded within the commune health system and is the lead
      mortality reporting system for the Ministry of Health. The system performs well
      in relation to its completeness and classification of injury related deaths. With
      further enhancements and ongoing support from government and donor agencies, the
      A6 system will be a valuable resource for identifying and planning preventive
      strategies targeting the leading causes of injury related deaths in Vietnam.

PMID- 22361246
TI  - Foodborne outbreaks of shigellosis in the USA, 1998-2008.
AB  - We examined reported outbreaks of foodborne shigellosis in the USA from 1998 to
      2008 and summarized demographic and epidemiological characteristics of 120
      confirmed outbreaks resulting in 6208 illnesses. Most reported foodborne
      shigellosis outbreaks (n = 70, 58%) and outbreak-associated illnesses (n = 3383,
      54%) were restaurant-associated. The largest outbreaks were associated with
      commercially prepared foods distributed in multiple states and foods prepared in
      institutional settings. Foods commonly consumed raw were implicated in 29 (24%)
      outbreaks and infected food handlers in 28 (23%) outbreaks. Most outbreaks (n =
      86, 72%) were caused by Shigella sonnei. Targeted efforts to reduce contamination
      during food handling at multiple points in the food processing and distribution
      system, including food preparation in restaurants and institutional settings,
      could prevent many foodborne disease outbreaks and outbreak-related illnesses
      including those due to Shigella.

PMID- 22361247
TI  - Five-year survival does not equal cure in non-small cell lung cancer: a
      Surveillance, Epidemiology, and End Results-based analysis of variables affecting
      10- to 18-year survival.
AB  - OBJECTIVE: Five-year survival after the diagnosis of non-small cell lung cancer
      is the most common benchmark used to evaluate long-term survival. Data on
      survival beyond 5 years are sparse. We sought to elucidate variables affecting 10
      to 18-year survival. METHODS: A total of 31,206 patients alive at least 5 years
      after diagnosis of non-small cell lung cancer who were registered in the
      Surveillance, Epidemiology, and End Results database from 1988 to 2001 were
      examined. Primary end points were disease-specific survival and overall survival.
      Survival analysis was performed with Kaplan-Meier estimates, multivariable Cox
      proportional hazards regression, and competing risk models. RESULTS: Overall
      survival at 10, 15, and 18 years was 55.4%, 33.1%, and 24.3%, respectively.
      Disease-specific survival at 10, 15, and 18 years was 76.6%, 65.4%, and 59.4%,
      respectively. In multivariable regression analysis, squamous cell cancers had a
      disease-specific survival advantage (hazard ratio, 0.88; P < .0001) but an
      overall survival disadvantage (hazard ratio, 1.082; P = .0002) compared with
      adenocarcinoma. Pneumonectomy (hazard ratio, 0.44) and lobectomy (hazard ratio,
      0.474) had improved disease-specific survival compared with no surgery (P <
      .0001). Left-sided tumors (hazard ratio, 0.723; P = .036) and node-negative
      cancers (hazard ratio, 0.562; P < .001) also had a better disease-specific
      survival and, to a lesser extent, overall survival advantage. CONCLUSIONS: Five
      year survivors of non-small cell lung cancer have a persistent risk of death from
      lung cancer up to 18 years from diagnosis. More than one half of all deaths in 5
      year survivors are related to lung cancer. In multivariable regression analysis,
      age, node-negative disease, and lobar or greater resection were strong predictors
      of long-term survival (ie, 10-18 years).

PMID- 22361248
TI  - Integrated morphologic and functional assessment of the aortic root after
      different tissue valve root replacement procedures.
AB  - OBJECTIVES: This study was undertaken to explore aspects of the hemodynamic
      function of different biologic tissue aortic valve root replacements. We set out
      to image and display the spatiotemporal distributions of axially directed blood
      velocity through the aortic root. METHODS: The flow velocities through a plane
      transecting the aortic root were measured by 2-dimensional cine phase-contrast
      magnetic resonance velocity mapping in 44 subjects: 29 patients who had undergone
      aortic root replacement approximately 10 years previously (13 autografts, 10
      stentless xenografts, and 6 homografts) and 15 healthy control subjects. With
      cine as well as velocity images, aortic sinus dimensions, effective orifice area,
      and several velocity parameters were measured. Color-coded plots of velocity
      relative to the sinus cross sections and velocity-time plots were used to compare
      spatiotemporal distributions of velocity. RESULTS: Peak flow velocity was similar
      between the autografts (102 +/- 28.0 cm/s) and control valves (119 +/- 20.0 cm/s)
      but was higher in xenografts (167 +/- 36.0 cm/s) and homografts (206 +/- 91.0
      cm/s). These measurements showed an inverse relationship with the effective
      orifice area (7.27 +/- 0.20, 4.24 +/- 0.81, 3.37 +/- 0.32, and 3.28 +/- 0.87
      cm(2), respectively). Autograft peak flow velocity showed no significant
      difference from control valve peak flow velocity, despite larger root dimensions
      (P < .001). The graphic displays provided further spatiotemporal information.
      CONCLUSIONS: Peak velocities and spatiotemporal flow patterns depend on the type
      of valve substitute. In the parameters measured, autograft replacements differed
      least from normal aortic valves.

PMID- 22361249
TI  - A simple and effective technique for identification of intersegmental planes by
      infrared thoracoscopy after transbronchial injection of indocyanine green.
AB  - OBJECTIVE: Pulmonary segmentectomy has been recognized as an operative option for
      complete resection of early-stage lung cancer in patients with poor pulmonary
      function. However, identification of anatomic pulmonary segments is sometimes
      difficult in patients with emphysema. We developed an intraoperative method for
      identifying intersegmental planes of the lung with high-sensitivity infrared
      fluorescence imaging after transbronchial injection of indocyanine green.
      METHODS: The study included 10 patients with early-stage lung cancer who
      underwent thoracoscopic segmentectomy. Under general anesthesia, indocyanine
      green was injected into the bronchus of target pulmonary segments. The target
      segments of the lung were identified using the indocyanine green fluorescence
      endoscope (Hamamatsu Photonics, Hamamatsu, Japan). The intersegmental lines and
      planes were identified and allowed removal of the segments. To evaluate operative
      outcomes, we compared the indocyanine green injection group with a retrospective
      control group with 10 matched-pair patients who underwent traditional
      thoracoscopic segmentectomy. RESULTS: Accurate, real-time intraoperative
      detection of indocyanine green with an infrared thoracoscope was confirmed.
      Sparing of intersegments was safely performed using both staples and electric
      cautery. Furthermore, infrared thoracoscopy allowed visualization of any residual
      portion of resected segments after segmentectomy. There was no difference between
      the experimental indocyanine green and control groups in terms of operative time,
      duration of postoperative chest drainage, or postoperative complications. Length
      of stay was shorter in the indocyanine green group than in the control group (P =
      .055). CONCLUSIONS: Transbronchial indocyanine green injection into the relevant
      bronchus with the use of an infrared thoracoscope allows identification of
      intersegmental lines and planes during thoracoscopic segmentectomy.

PMID- 22361250
TI  - Video-assisted thoracoscopic surgery with spontaneous breathing laryngeal mask
      anesthesia: preliminary experience.

PMID- 22361252
TI  - Prognosis and treatment of acute hydrocephalus following aneurysmal subarachnoid
      haemorrhage.
AB  - The aim of this study was to determine the rate of acute hydrocephalus in
      patients with aneurysmal subarachnoid haemorrhage (SAH) and evaluate its clinical
      prognosis and treatment options. We recruited 152 patients who had ruptured
      cerebral aneurysms between 2006 and 2010. Sequential CT scans were performed 24
      72 hours after haemorrhage to examine the development of acute hydrocephalus
      following aneurysmal SAH. If hydrocephalus was present but the patient's
      condition was stable, the patient was closely monitored for 48 hours before
      undergoing a repeat CT scan to evaluate ventricular changes. To exclude aneurysm
      rebleeding, repeat CT scans were performed frequently in patients who continued
      to deteriorate clinically, and external ventricular drainage was performed if the
      deterioration was due to worsening hydrocephalus. In clinically stable patients
      with persistent hydrocephalus and patients with external ventricular drainage,
      lamina terminalis fenestration was performed during aneurysm clipping, and the
      procedure's therapeutic efficacy was evaluated at the postoperative follow-up.
      The overall incidence of acute hydrocephalus following aneurysmal SAH was 17.8%
      (27/152). Of these patients, 29.6% (eight of 27) recovered spontaneously within
      48 hours of hydrocephalus development, 37.0% (10/27) required external
      ventricular drainage, and 33.3% (nine of 27) remained clinically stable with
      persistent hydrocephalus during the observational period. Hydrocephalus was
      significantly alleviated in eight of 11 patients who underwent lamina terminalis
      fenestration, and no related complications were observed during follow-up. Three
      patients, for whom intraoperative fenestration was ineffective, underwent shunt
      surgery. Our results showed approximately 30% of patients with acute
      hydrocephalus following aneurysmal SAH recover spontaneously. In the majority of
      patients with persistent hydrocephalus, lamina terminalis fenestration performed
      during aneurysm clipping is effective. Ventriculoperitoneal shunting can be
      considered in the remaining patients.

PMID- 22361251
TI  - Efficacy of early neonatal vitamin A supplementation in reducing mortality during
      infancy in Ghana, India and Tanzania: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Vitamin A supplementation of 6-59 month old children is currently
      recommended by the World Health Organization based on evidence that it reduces
      mortality. There has been considerable interest in determining the benefits of
      neonatal vitamin A supplementation, but the results of existing trials are
      conflicting. A technical consultation convened by WHO pointed to the need for
      larger scale studies in Asia and Africa to inform global policy on the use of
      neonatal vitamin A supplementation. Three trials were therefore initiated in
      Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU)
      given to neonates once orally on the day of birth or within the next two days
      will reduce mortality in the period from supplementation to 6 months of age
      compared to placebo. METHODS/DESIGN: The trials are individually randomized,
      double masked, and placebo controlled. The required sample size is 40,200 in
      India and 32,000 each in Ghana and Tanzania. The study participants are neonates
      who fulfil age eligibility, whose families are likely to stay in the study area
      for the next 6 months, who are able to feed orally, and whose parent(s) provide
      informed written consent to participate in the study. Neonates randomized to the
      intervention group receive 50,000 IU vitamin A and the ones randomized to the
      control group receive placebo at the time of enrollment. Mortality and morbidity
      information are collected through periodic home visits by a study worker during
      infancy. The primary outcome of the study is mortality from supplementation to 6
      months of age. The secondary outcome of the study is mortality from
      supplementation to 12 months of age. The three studies will be analysed
      independent of each other. Subgroup analysis will be carried out to determine the
      effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and
      maternal large-dose vitamin A supplementation. DISCUSSION: The three ongoing
      studies are the largest studies evaluating the efficacy of vitamin A
      supplementation to neonates. Policy formulation will be based on the results of
      efficacy of the intervention from the ongoing randomized controlled trials
      combined with results of previous studies.

PMID- 22361253
TI  - Action verb understanding in first-episode schizophrenia: is there evidence for a
      simulation deficit?
AB  - Schizophrenia is often associated with deficits in the domain of language, which
      are thought to be closely related to deficits in the structure of semantic
      knowledge. The main aim of the present study was to behaviorally investigate
      whether semantic impairments in schizophrenia are present also at the very basic
      level of action verb processing, in particular at the level of motor simulation.
      We used a go-no go paradigm both for a semantic decision task (with either an
      early, EGD, or a delayed go-signal delivery, DGD) and for a lexical decision task
      (control task). Only the first task requires motor simulation to be solved. We
      found that first-episode schizophrenia (FES) patients, like healthy control (HC)
      participants, use motor simulation as a basic strategy to semantically judge
      action verbs. In the EGD condition, both motor simulation and action verb
      understanding seem to be preserved in FES. However, differently from HC
      participants, FES patients kept on using the simulation strategy also with the
      DGD condition, whereas, simultaneously, task performance during this condition
      appeared to be less efficient and sensitive. Voxel-based morphometry analysis
      suggested that this altered performance in FES patients could be related to
      structural brain abnormalities in the right dorsolateral prefrontal cortex. We
      propose that a prolonged motor simulation in FES may serve as a compensatory
      strategy for impairments in the selection of action representation and/or for
      memory deficits disclosed by the DGD condition during the semantic decision task
      investigated in the present study.

PMID- 22361254
TI  - Trans-saccadic priming in hemianopia: sighted-field sensitivity is boosted by a
      blind-field prime.
AB  - We experience visual stability despite shifts of the visual array across the
      retina produced by eye movements. A process known as remapping is thought to keep
      track of the spatial locations of objects as they move on the retina. We explored
      remapping in damaged visual cortex by presenting a stimulus in the blind field of
      two patients with hemianopia. When they executed a saccadic eye movement that
      would bring the stimulated location into the sighted field, reported awareness of
      the stimulus increased, even though the stimulus was removed before the saccade
      began and so never actually fell in the sighted field. Moreover, when a location
      was primed by a blind-field stimulus and then brought into the sighted field by a
      saccade, detection sensitivity for near-threshold targets appearing at this
      location increased dramatically. The results demonstrate that brain areas
      supporting conscious vision are not necessary for remapping, and suggest visual
      stability is maintained for salient objects even when they are not consciously
      perceived.

PMID- 22361255
TI  - Physical environmental factors related to walking and cycling in older adults:
      the Belgian aging studies.
AB  - BACKGROUND: Socio-ecological models emphasize the relationship between the
      physical environment and physical activity (PA). However, knowledge about this
      relationship in older adults is limited. Therefore, the present study aims to
      investigate the relationship between area of residence (urban, semi-urban or
      rural) and older adults' walking and cycling for transportation and recreation.
      Additionally, relationships between several physical environmental factors and
      walking and cycling and possible moderating effects of area of residence, age and
      gender were studied. METHODS: Data from 48,879 Flemish older adults collected in
      2004-2010 through peer research were analyzed. Walking, cycling and environmental
      perceptions were assessed using self-administered questionnaires. The Study
      Service of the Flemish Government provided objective data on municipal
      characteristics. Multilevel logistic regression analyses were applied. RESULTS:
      Urban participants were more likely to walk daily for transportation compared to
      rural (OR = 1.43; 95% CI = 1.22, 1.67) and semi-urban participants (OR = 1.32;
      95% CI = 1.13, 1.54). Urban participants were less likely to cycle daily for
      transportation compared to semi-urban participants (OR = 0.72; 95% CI = 0.56,
      0.92). Area of residence was unrelated to weekly recreational walking/cycling.
      Perceived short distances to services (ORs ranging from 1.04 to 1.19) and
      satisfaction with public transport (ORs ranging from 1.07 to 1.13) were
      significantly positively related to all walking/cycling behaviors. Feelings of
      unsafety was negatively related to walking for transportation (OR = 0.93, 95% CI
      = 0.91, 0.95) and recreational walking/cycling (OR = 0.95, 95% CI = 0.92, 0.97).
      In females, it was also negatively related to cycling for transportation (OR =
      0.94, 95% CI = 0.90, 0.98). CONCLUSIONS: Urban residents were more likely to walk
      for transportation daily compared to semi-urban and rural residents. Daily
      cycling for transportation was less prevalent among urban compared to semi-urban
      residents. Access to destinations appeared to be important for promoting both
      walking and cycling for transportation and recreation across all demographic
      subgroups. Additionaly, feelings of unsafety were associated with lower rates of
      walking for transportation and walking/cycling for recreation in all subgroups
      and cycling for transportation in females. No clear patterns emerged for other
      environmental factors.

PMID- 22361256
TI  - Changes in reward-related signals in the rat nucleus accumbens measured by in
      vivo oxygen amperometry are consistent with fMRI BOLD responses in man.
AB  - Real-time in vivo oxygen amperometry, a technique that allows measurement of
      regional brain tissue oxygen (O(2)) has been previously shown to bear
      relationship to the BOLD signal measured with functional magnetic resonance
      imaging (fMRI) protocols. In the present study, O(2) amperometry was applied to
      the study of reward processing in the rat nucleus accumbens to validate the
      technique with a behavioural process known to cause robust signals in human
      neuroimaging studies. After acquisition of a cued-lever pressing task a robust
      increase in O(2) tissue levels was observed in the nucleus accumbens specifically
      following a correct lever press to the rewarded cue. This O(2) signal was
      modulated by cue reversal but not lever reversal, by differences in reward
      magnitudes and by the motivational state of the animal consistent with previous
      reports of the role of the nucleus accumbens in both the anticipation and
      representation of reward value. Moreover, this modulation by reward value was
      related more to the expected incentive value rather than the hedonic value of
      reward, also consistent with previous reports of accumbens coding of "wanting" of
      reward. Altogether, these results show striking similarities to those obtained in
      human fMRI studies suggesting the use of oxygen amperometry as a valid surrogate
      for fMRI in animals performing cognitive tasks, and a powerful approach to bridge
      between different techniques of measurement of brain function.

PMID- 22361257
TI  - Epidemiological concordance of Japanese encephalitis virus infection among
      mosquito vectors, amplifying hosts and humans in India.
AB  - A temporal relationship of Japanese encephalitis virus (JEV) transmission in
      pigs, mosquitoes and humans revealed that sentinel pig seroconversions were
      significantly associated with human cases 4 weeks before (P = 0.04) their
      occurrence, highly correlated during the same time and 2 weeks before case
      occurrence (P < 0.001), and remained significantly correlated up to 2 weeks after
      human case occurrence (P < 0.01). JEV was detected in the same month in pigs and
      mosquitoes, and peaks of pig seroconversion were preceded by 1-2 months of peaks
      of infection in vectors. Kaplan-Meier analysis indicated that detection of JEV
      positive mosquitoes was significantly associated with the median time to
      occurrence of seroconversion in pigs (P < 0.05). This study will not only help in
      predicting JEV activity but also accelerate timely vector control measures and
      vaccination programmes for pigs and humans to reduce the Japanese encephalitis
      risk in endemic areas.

PMID- 22361258
TI  - Does maternal depression predict developmental outcome in 18 month old infants?
AB  - AIM: Our aim was to examine the associations between maternal depression in the
      first 6 months postpartum, home environment and cognitive, language and motor
      development in infants at 18 months of age. STUDY DESIGN AND METHODS: This
      article reports results from the control group (n=312 full term; n=48 preterm) of
      the prospective Docosahexaenoic acid (DHA) to Optimise Maternal Infant Outcome
      (DOMInO) Randomised Controlled Trial. Mothers in South Australia completed the
      Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks and 6 months postpartum.
      Infant development was assessed when children were 18 months old with the Bayley
      Scales of Infant and Toddler Development Version III and mothers completed the
      Home Screening Questionnaire at this assessment. RESULTS: There were no
      significant associations between maternal depression in the first 6 months
      postpartum and cognitive, language or motor development after controlling for
      infant prematurity, breastfeeding status and socio-economic level. Home
      environment remained a significant predictor of development after controlling for
      potential confounding variables. Using mediation models, we did not find an
      association between maternal depression and developmental outcome through home
      environment. CONCLUSIONS: Maternal depression in the first 6 months postpartum
      was not associated with infant development at 18 months of age. Further studies
      should focus on women with chronic depression.

PMID- 22361259
TI  - Depression and anxiety in women during pregnancy and neonatal outcome: data from
      the EDEN mother-child cohort.
AB  - BACKGROUND: According to the World Health Organization, mental health disorders
      are the leading causes of disease burden in women from 15 to 44 years. These
      conditions in pregnant women may affect the offspring. AIM: To analyze the
      relation between depression and anxiety of pregnant women and neonatal outcomes
      including gestational age and birthweight. STUDY DESIGN: Observational cohort
      study. SUBJECTS: 2002 women recruited before the 20th gestational week. OUTCOME
      MEASURES: Gestational age at delivery in completed weeks of amenorrhea and
      preterm delivery defined as birth before 37 completed weeks of gestation.
      Spontaneous preterm birth (PB) defined as either spontaneous preterm labor or
      preterm premature rupture of the membranes. Medically indicated preterm delivery
      defined as delivery that begins by induction or cesarean section. Birthweight as
      a continuous variable and centiles of the customized fetal weight norms for the
      French population. RESULTS: From the 1719 women included in the study, 7.9%
      (n=135) were classified as "anxious", 11.8% (n=203) as "depressed", 13.2% (n=227)
      as "depressed and anxious". After adjusting for potential confounders, depression
      combined with anxiety during pregnancy increased the risk of spontaneous PB (Odds
      Ratio: 2.46 [1.22-4.94]), but did not influence medically indicated PB nor
      birthweight. CONCLUSION: In this study, comorbidity of depressive and anxiety
      symptoms was the worst condition during pregnancy. Further studies are needed to
      investigate depression and anxiety together to improve the comprehension of the
      biological modifications involved.

PMID- 22361260
TI  - Attitudes among medical and nonmedical university students toward the survivors
      of childhood abuse.
AB  - OBJECTIVE: Childhood sexual abuse (CSA) is increasing, and current studies should
      address issues such as stigmas and casual attitudes that may be amenable to
      intervention. Thus, we aimed to investigate the effects of education on the
      attitudes of medical students toward CSA survivors. METHOD: We divided medical
      students into 2 groups: preclinical and clinical medical students. We compare the
      attitudes of nonmedical students with the attitudes of medical students with
      respect to survivors of CSA. All participants were asked to complete a
      questionnaire about stigmatization. RESULTS: There were 572 students in our
      study, 347 of whom were enrolled in medical school. Of the 347 medical students,
      151 were from the preclinical group, and 196 were from the clinical practice
      group. The remainder of the participants (n = 225) were in other fields of
      university. Of the medical students, 68.3% responded negatively about "asking a
      survivor of abuse to supervise their child for a few hours," whereas 62.7% of the
      nonmedical students responded negatively. When asked, "What would you think if
      your child wanted to marry a survivor of sexual abuse?", 72.9% of the medical
      students and 59.1% of the nonmedical students displayed negative attitudes toward
      that idea. Our research also found that significantly more preclinical students
      than clinical students would not want to be in a companionship/friendship with a
      CSA survivor at work (P = .015) or in their neighborhoods (P = .034). CONCLUSION:
      Both medical and nonmedical students seem to have negative thoughts about sexual
      abuse survivors, particularly when the issue involves their own children and/or
      social situations. Thus, the medical professionals must be careful and should
      avoid over interpretations of findings on childhood abuse studies that may lead
      to stigmatization.

PMID- 22361261
TI  - Gastric emptying and symptoms of bulimia nervosa: effect of a prokinetic agent.
AB  - OBJECTIVE: Previous studies have suggested that delayed gastric emptying and
      abnormal postprandial release of hormones that influence satiation, particularly
      cholecystokinin (CCK), may play an important role in the pathophysiology of
      bulimia nervosa (BN). This study was designed to test these hypotheses as well as
      the efficacy of the prokinetic agent erythromycin in patients with BN. METHOD:
      Thirty-two normal-weight women with BN and 24 control participants consumed a
      large liquid test meal. Gastric emptying and pre- and postprandial release of
      CCK, peptide YY (PYY), and ghrelin were determined. Participants with BN were
      then recruited for double-blind treatment with erythromycin up to 500 mg three
      times daily vs. placebo for 6 weeks, following which they consumed a repeat test
      meal with gastric emptying and appetitive hormone measurements. RESULTS: CCK
      release at 15 min following the meal was marginally lower (p=0.1) in BN than in
      control participants. Rate of gastric emptying and postprandial hormone release
      were similar in BN and controls. BN patients assigned to erythromycin compared to
      those assigned to placebo had more rapid gastric emptying following treatment,
      but there were no differences in release of CCK, PYY, or ghrelin following the
      post-treatment test meal. Moreover, treatment with erythromycin was not
      associated with clinical response. DISCUSSION: The current study does not support
      the clinical utility of moderate dose erythromycin in treating BN. Furthermore,
      the findings suggest that a modest increase in gastric emptying rate is
      associated neither with altered postprandial hormonal release nor with clinical
      benefit in these patients. While providing no evidence for the effectiveness of
      prokinetic agents in this setting, our findings do not preclude the possibility
      that a greater increase in gastric emptying rate might prove beneficial.

PMID- 22361262
TI  - Effects of leptin treatment and Western diet on wheel running in selectively bred
      high runner mice.
AB  - The role of leptin in regulating physical activity is varied. The behavioral
      effects of leptin signaling depend on the type of activity and the animal's
      physiological state. We used mice from lines selectively bred for high voluntary
      wheel running to further study how leptin regulates volitional exercise. Mice
      from four replicate high runner (HR) lines typically run ~3-fold more revolutions
      per day than those from four non-selected control (C) lines. HR mice have altered
      dopamine function and differences from C in brain regions known to be important
      in leptin-mediated behavior. Furthermore, male HR mice have been found to
      dramatically increase running when administered Western diet, an effect possibly
      mediated through leptin signaling. Male mice from generation 61 (representing
      three HR lines and one C line) were allowed wheel access at 24 days of age and
      given either Western diet (high in fat and with added sucrose) or standard chow.
      After four weeks, Western diet significantly increased circulating leptin,
      insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone
      resistin concentrations in HR mice (C mice not measured). Western diet increased
      running in HR mice, but did not significantly affect running in C mice. During
      the fifth week, all mice received two days of intra-peritoneal sham injections
      (physiological saline) followed by three days of murine recombinant leptin
      injections, and then another six days of sham injections. Leptin treatment
      significantly decreased caloric intake (adjusted for body mass) and body mass in
      all groups. Wheel running significantly increased with leptin injections in HR
      mice (fed Western or standard diet), but was unaffected in C mice. Whether
      Western diet and leptin treatment stimulate wheel running in HR mice through the
      same physiological pathways awaits future study. These results have implications
      for understanding the neural and endocrine systems that control locomotor
      activity, food consumption, and body weight, and how they may vary with genetic
      background.

PMID- 22361263
TI  - Short-term testosterone manipulations modulate visual recognition memory and some
      aspects of emotional reactivity in male rhesus monkeys.
AB  - The role of testosterone (T) in modulating cognitive function and emotion in men
      remains unclear. The paucity of animal studies has likely contributed to the slow
      progress in this area. In particular, studies in nonhuman primates have been
      lacking. Our laboratory has begun to address this issue by pharmacologically
      manipulating T levels in intact male rhesus monkeys, using blind, placebo
      controlled, crossover designs. We previously found that T-suppressed monkeys
      receiving supraphysiological T for 4 weeks had lower visual recognition memory
      for long delays and enhanced attention to videos of negative social stimuli
      (Lacreuse et al., 2009, 2010) compared to when treated with oil. To further
      delineate the conditions under which T affects cognition and emotion, the present
      study focused on the short-term effects of physiological T. Six intact males were
      treated with the gonadotropin-releasing hormone antagonist degarelix (3 mg/kg)
      for 7 days and received one injection of T enanthate (5 mg/kg) followed by one
      injection of oil vehicle 7 days later (n=3), or the reverse treatment (n=3).
      Performance on two computerized tasks, the Delayed-non-matching-to-sample (DNMS)
      with random delays and the object-Delayed Recognition Span test (object-DRST) and
      one task of emotional reactivity, an approach/avoidance task of negative,
      familiar and novel objects, was examined at baseline and 3-5 days after
      treatment. DNMS performance was significantly better when monkeys were treated
      with T compared to oil, independently of the delay duration or the nature
      (emotional or neutral) of the stimuli. Performance on the object-DRST was
      unaffected. Interestingly, subtle changes in emotional reactivity were also
      observed: T administration was associated with fewer object contacts, especially
      on negative objects, without overt changes in anxious behaviors. These results
      may reflect increased vigilance and alertness with high T. Altogether, the data
      suggest that changes in general arousal may underlie the beneficial effects of T
      on DNMS performance. This hypothesis will require further study with objective
      measures of physiological arousal.

PMID- 22361264
TI  - The orexin-1 receptor antagonist SB-334867 decreases sympathetic responses to a
      moderate dose of methamphetamine and stress.
AB  - We recently discovered that inhibiting neurons in the dorsomedial hypothalamus
      (DMH) attenuated hyperthermia, tachycardia, hypertension, and hyperactivity
      evoked by the substituted amphetamine 3, 4-methylenedioxymethamphetamine (MDMA).
      Neurons that synthesize orexin are also found in the region of the DMH. As orexin
      and its receptors are involved in the regulation of heart rate and temperature,
      they would seem to be logical candidates as mediators of the effects evoked by
      amphetamines. The goal of this study was to determine if blockade of orexin-1
      receptors in conscious rats would suppress cardiovascular and thermogenic
      responses evoked by a range of methamphetamine (METH) doses. Male Sprague-Dawley
      rats (n=6 per group) were implanted with telemetric transmitters measuring body
      temperature, heart rate, and mean arterial pressure. Animals were randomized to
      receive pretreatment with either the orexin-1 receptor antagonist SB-334867
      (10mg/kg) or an equal volume of vehicle. Thirty minutes later animals were given
      intraperitoneal (i.p.) injections of either saline, a low (1mg/kg), moderate
      (5mg/kg) or high (10mg/kg) dose of METH. Pretreatment with SB-334867
      significantly attenuated increases in body temperature and mean arterial pressure
      evoked by the moderate but not the low or high dose of METH. Furthermore, animals
      treated with SB-334867, compared to vehicle, had lower temperature and heart rate
      increases after the stress of an i.p. injection. In conclusion, temperature and
      cardiovascular responses to a moderate dose of METH and to stress appear to
      involve orexin-1 receptors. The failure to affect a low and a high dose of METH
      suggests a complex pharmacology dependent on dose. A better understanding of this
      may lead to the knowledge of how monoamines influence the orexin system and vice
      versa.

PMID- 22361266
TI  - Comparison of coherence and phase synchronization of the human sleep
      electroencephalogram.
AB  - OBJECTIVE: Potential differences between coherence and phase synchronization
      analyses of human sleep electroencephalogram (EEG) are assessed and occurrences
      of phase vs. complete synchronization between EEG signals from different
      locations during different sleep stages are investigated. METHODS: Linear
      spectral coherence, mean phase coherence (MPC) z-score and Pearson's correlation
      coefficient of analytic amplitudes were evaluated for different spectral bands of
      whole-night EEG recordings from 25 healthy subjects. RESULTS: Coherence and MPC z
      score demonstrated practically the same statistical differences between vigilance
      stages, confirming the findings of previous coherence-based studies. MPC z-score
      and amplitude correlations were most correlated (>0.5) between homologous
      interhemispheric positions and least correlated between nonhomologous
      interhemispheric positions and between fronto-occipital positions. CONCLUSIONS:
      Coherence and phase synchronization provided essentially the same information.
      Complete synchronization was manifested by highly coherent phases and correlated
      amplitudes, as well as by correlated changes of phase synchronization, coherence
      and amplitude correlations between vigilance states. In cases of weaker coupling,
      phase synchronization and coherence change in agreement, while behaviour of
      amplitude correlations differs. SIGNIFICANCE: Phase synchronization analysis is
      not superior to coherence analysis, although the coupling between EEG signals is
      dominated by phase synchronization which turns into complete synchronization in
      the most strongly coupled EEG signals.

PMID- 22361265
TI  - Residual brain dysfunction observed one year post-mild traumatic brain injury:
      combined EEG and balance study.
AB  - OBJECTIVES: There is still considerable debate and controversy about whether EEG
      can be used as a robust clinical tool for assessment of mild traumatic brain
      injury (MTBI). Nonhomogeneous subject populations, inaccurate assessment of
      severity of brain injury, time since injury when EEG testing was performed, the
      lack of EEG research conducted serially and in conjunction with other behavioral
      measures as injury evolves over time may contribute to the existing
      controversies. In this study, we implemented a concussion assessment protocol
      combining a series of EEG and balance measures throughout one year post-injury to
      document the efficacy of EEG and balance measures as relate to differential
      recovery of patients suffering from MTBI. METHODS: Three hundred and eighty
      subjects at risk for MTBI were initially recruited for baseline testing. Forty
      nine from this initial subjects pool subsequently suffered a single episode of
      concussive blow and were tested on day 7, 15, 30 days, 6 months and 12 months
      post-injury. EEGs were recorded while sitting, standing on the force plate and
      then on a foam base of support with eyes open/closed conditions. EEG alpha power
      (8-12 Hz) and its percent suppression from sitting to standing postures were
      computed. The center of pressure (COP) measures were obtained from the force
      platform and analyzed for eyes open and eyes closed conditions. RESULTS: Percent
      alpha power suppression from sitting to standing postural conditions
      significantly increased in MTBI subjects shortly after the injury (p<0.01).
      Percent alpha power suppression significantly correlated with increased area of
      COP during standing posture with eye closed (r(2)=0.53, p<0.01). The magnitude of
      alpha power suppression predicted the rate of recovery of this measure in sub
      acute and chronic phases of injury (r(2)=0.609, p<0.01). Finally, 85% of MTBI
      subjects who showed more than 20% of alpha power suppression in the acute phase
      of injury did not return to pre-injury status up to 12 months post-injury.
      CONCLUSIONS: The efficacy of serially implemented EEG measures in conjunction
      with balance assessment over the course of MTBI evolution to document residual
      cerebral dysfunction was demonstrated. Specifically, alteration of EEG alpha
      power dynamics in conjunction with balance data in the acute phase of injury with
      respect to baseline measures may predict the rate of recovery from a single
      concussive blow. SIGNIFICANCE: Neurophysiological measures are excellent tools to
      assess the status and prognosis of patients with MTBI.

PMID- 22361268
TI  - Sjogren's syndrome: an update on clinical, basic and diagnostic therapeutic
      aspects.
AB  - The 11th International Symposium for Sjogren's syndrome was held in Athens,
      Greece in September 2011. This symposia is part of a long series of meetings that
      have attempted to meet the needs of both scientists and physicians in improving
      the healthcare of their patients with Sjogren's syndrome. Sjogren's syndrome
      affects almost 0.5% of the general population and is second only to rheumatoid
      arthritis amongst the systemic autoimmune diseases. More importantly, it has
      daily implications for the millions of sufferers around the world. The goal of
      this meeting, which included nearly 200 abstracts and invited lectures, was to
      address the critical needs in the clinical practice of Sjogren's syndrome. This
      volume is a composite of select papers that were presented at this meeting and
      attempts to provide a critical overview of clinical and basic science. The volume
      includes a variety of themes and, importantly, raises issues that are still
      unresolved but which are important in our future diagnostic and therapeutic
      efforts.

PMID- 22361269
TI  - Velocity of mist droplets and suspending gas imaged separately.
AB  - Nuclear Magnetic Resonance Images (MRIs) of the velocity of water droplets and
      velocity of the suspending gas, hexafluoroethane, are presented for a vertical
      and horizontal mist pipe flow. In the vertical flow, the upward velocity of the
      droplets is clearly slower than the upward velocity of the gas. The average
      droplet size calculated from the average falling velocity in the upward flow is
      larger than the average droplet size of mist drawn from the top of the pipe
      measured with a multi-stage aerosol impactor. Vertical flow concentrates larger
      particles because they have a longer transit time through the pipe. In the
      horizontal flow there is a gravity-driven circulation with high-velocity mist in
      the lower portion of the pipe and low-velocity gas in the upper portion. MRI has
      the advantages that it can image both phases and that it is unperturbed by
      optical opacity. A drawback is that the droplet phase of mist is difficult to
      image because of low average spin density and because the signal from water
      coalesced on the pipe walls is high. To our knowledge these are the first NMR
      images of mist.

PMID- 22361267
TI  - A rule-based seizure prediction method for focal neocortical epilepsy.
AB  - OBJECTIVE: In the present study, we have developed a novel patient-specific rule
      based seizure prediction system for focal neocortical epilepsy. METHODS: Five
      univariate measures including correlation dimension, correlation entropy, noise
      level, Lempel-Ziv complexity, and largest Lyapunov exponent as well as one
      bivariate measure, nonlinear interdependence, were extracted from non-overlapping
      10-s segments of intracranial electroencephalogram (iEEG) data recorded using
      electrodes implanted deep in the brain and/or placed on the cortical surface. The
      spatio-temporal information was then integrated by using rules established based
      on patient-specific changes observed in the period prior to a seizure sample for
      each patient. The system was tested on 316 h of iEEG data containing 49 seizures
      recorded in 11 patients with medically intractable focal neocortical epilepsy.
      RESULTS: For seizure occurrence periods of 30 and 50 min our method showed an
      average sensitivity of 79.9% and 90.2% with an average false prediction rate of
      0.17 and 0.11/h, respectively. In terms of sensitivity and false prediction rate,
      the system showed superiority to random and periodical predictors. CONCLUSIONS:
      The nonlinear analysis of iEEG in the period prior to seizures revealed patient
      specific spatio-temporal changes that were significantly different from those
      observed within baselines in the majority of the seizures analyzed in this study.
      SIGNIFICANCE: The present results suggest that the patient specific rule-based
      approach may become a potentially useful approach for predicting seizures prior
      to onset.

PMID- 22361270
TI  - Correlation of the inhomogeneous field as a measure of sample heterogeneity.
AB  - In this paper we present a method to determine the pore and grain size
      heterogeneity using a correlation between the transverse relaxation time and the
      susceptibility induced inhomogeneous magnetic field. By using a CPMG echo train,
      we are able to correlate T(2) with the inhomogeneous internal magnetic field,
      B(z)(i). We first introduce a simple simulation to study the correlation between
      the internal magnetic field gradient, ?g?, and B(z)(i), where this correlation is
      analogous to the T(2)-B(z)(i) correlation with horizontal inversion. We then
      acquire experimental data from two samples, one a simple bead pack, and the other
      a more complicated sandstone rock core. We find that indeed this method can
      indicate the presence of pore and grain size heterogeneities in the sample.

PMID- 22361271
TI  - Pleural malakoplakia caused by Rhodococcus equi infection in a patient after stem
      cell transplantation.
AB  - Malakoplakia is a disease especially of the urinary tract with typical plaques
      most frequently observed in the urinary bladder's mucosa. In the context of
      immunosuppression malakoplakia can also occur in other organs. Some of these
      extravesical malakoplakias are associated with an infection by Rhodococcus equi,
      a rare human pathogen well known from veterinary medicine. Here we present the
      first case of a pleural malakoplakia without lung involvement caused by a proved
      Rhodococcus equi infection.

PMID- 22361272
TI  - Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives
      as potential EGFR and HER-2 kinase inhibitors.
AB  - A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and
      synthesized and their biological activities were also evaluated as potential EGFR
      and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for
      the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro
      1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory
      activity (IC(50)=0.24MUM for EGFR and IC(50)=1.07MUM for HER-2).
      Antiproliferative assay results indicated that compound E28 owned high
      antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with
      IC(50) value of 0.30, 0.54, and 0.70MUM, respectively. Docking simulation was
      further performed to position compound E28 into the EGFR active site to determine
      the probable binding model. Based on the preliminary results, compound E28 with
      potent inhibitory activity in tumor growth would be a potential anticancer agent.

PMID- 22361273
TI  - Anti-mycobacterial activities of some cationic and anionic calix[4]arene
      derivatives.
AB  - Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents
      against Mycobacterium tuberculosis, H(37)Rv strain. The sulfonate, carboxylate
      and phosphonate anionic species displayed no activity. Cationic derivatives
      integrating four aminoethyl groups at the upper rim and two 6,6'-dimethyl-2,2'
      bipyridyl- or 4,4'-dimethyl-2,2'-bithiazolyl subunits at the lower rim were also
      found inactive against M. tuberculosis, while the unsubstituded and the 5,5'
      dimethyl-2,2'-bipyridyl-analogues exhibited MIC values of 3.2 and 0.8MUM
      respectively. Introduction of guanidinoethyl groups at the upper rim resulted,
      except for the 6,6'-dimethyl-2,2'-bipyridyl-derivative, in high anti
      mycobacterial activities for the unsubstituted, the 5,5'-dimethyl-2,2'-bipyridyl-
      and the 4,4'-dimethyl-2,2'-bithiazolyl analogues, with MIC values of 0.8, 0.8 and
      1.6MUM, respectively, similar to those of current commercial anti-tuberculosis
      agents. The five more active substances were also evaluated against the isoniazid
      resistant strain MYC5165, resulting in highly interesting micromolar or sub
      micromolar MIC and IC(50), ca. 4-125 times more active than isoniazid. These
      preliminary results are attractive for the development of new anti-TB agents.

PMID- 22361274
TI  - Does processing of emotional facial expressions depend on intention? Time
      resolved evidence from event-related brain potentials.
AB  - We assessed the automaticity of emotional face processing with respect to the
      intentionality criterion, holding that automatic processes are triggered
      independently of intention. For this purpose, we observed emotion processing in
      event-related brain potential (ERP) components under five different task
      conditions. ERP components included the P1, N170, the early posterior negativity
      (EPN), and the late positive complex (LPC). Enhanced processing at perceptual
      stages as indicated by P1, N170, and EPN effects occurred independently of
      intention in angry expressions. In contrast, the emotion-related LPC, a putative
      manifestation of higher-level, more elaborative processing stages, depended on
      the intentional state of the participants. This suggests an automatic threat
      related processing bias at perceptual stages, while higher cognitive emotion
      encoding is subject to voluntary control. Moreover, an independent component
      analyses (ICA) showed that EPN and LPC activity occurred simultaneously,
      indicating perceptual and higher cognitive emotion encoding to occur in parallel.

PMID- 22361275
TI  - Transient trifascicular block secondary to tricuspid valve endocarditis.

PMID- 22361278
TI  - In the diagnosis of achalasia, "classic" might be "atypical".

PMID- 22361277
TI  - Efficacy of endoscopic closure of acute perforations of the gastrointestinal
      tract.
AB  - BACKGROUND & AIMS: Acute perforations of the gastrointestinal tract are rare,
      severe complications of endoscopy that usually require surgical repair.
      Endoscopic repair of perforations would reduce the need for surgeries; we
      evaluated the efficacy and safety of endoscopic closure of acute perforations of
      the gastrointestinal tract by using a new clip device. METHODS: We conducted a
      prospective, international, multicenter study of 36 consecutive patients (15
      male) with acute iatrogenic perforations (5 esophageal, 6 gastric, 12 duodenal,
      and 13 colonic perforation). Endoscopic repair was performed by using the Over
      the-Scope-Clip according to a standardized operating procedure. Primary end point
      was successful closure, which was determined as endoscopic successful closure
      without leakage (detected by water-soluble contrast x-ray analysis), and absence
      of adverse events within 30 days after the procedure. RESULTS: Immediate closure
      was endoscopically successful in 33 patients (92%). One patient developed an
      esophageal perforation while the cap was introduced, and in 2 patients the
      perforations did not close; these 3 patients were successfully treated with
      surgery. None of the patients had leakage of soluble contrast on the basis of
      contrast x-ray. One patient with a closed colonic perforation deteriorated
      clinically within 6 hours after the procedure. Despite surgery, the patient died
      within 36 hours. The remaining 32 patients had successful endoluminal closures;
      the overall success rate was 89% (95% confidence interval, 75%-96%). The mean
      endoscopic closure time was 5 minutes 44 seconds +/- 4 minutes 15 seconds.
      CONCLUSIONS: The Over-the-Scope-Clip is effective for endoluminal closure of
      acute iatrogenic perforations. It allows patients to avoid surgery, and 89% of
      patients had successful closures without adverse events.

PMID- 22361279
TI  - Rat Mrp2 gene expression is regulated by an interleukin-1beta-stimulated biphasic
      response with enhanced transcription and subcellular shuttling of YB-1.
AB  - INTRODUCTION: Expression of hepatobiliary transporters is decreased during
      endotoxemia. Reduction of Mrp2 is mediated by IL-1beta-dependent signals but
      underlying mechanisms are still unclear. YB-1 is a predominantly cytoplasmic
      protein that translocates to the nucleus in response to various stimuli.
      Previously we have shown that YB-1 down-regulates Mrp2 expression in vitro.
      Therefore we investigated the potential role of YB-1 as regulator of hepatic
      acute phase genes. METHODS: Liver sections from LPS-injected rats (20 h) were
      stained with YB-1-specific antibodies. Real-time RT-PCR quantification was
      performed for Mrp2, MMP-2 and YB-1. YB-1 protein was quantified from IL-1beta- or
      TNFalpha-stimulated rat hepatoma cells (FaO) and the localization of a YFP-YB-1
      CFP fusion protein was visualized by confocal microscopy in HepG2 human
      hepatocellular carcinoma cells. ChIP-assays and EMSA were performed to analyze YB
      1 binding to DNA promoter elements. RESULTS: In endotoxemic livers Mrp2 mRNA was
      down-regulated by 80%, while YB-1 mRNA expression increased 2.5-fold.
      Immunohistochemical staining showed a marked up-regulation and predominant
      nuclear localization of YB-1 protein in LPS challenged rats. In FAO cells IL
      1beta incubation increased cytoplasmic YB-1 protein content up to 16h. IL-1beta
      stimulation resulted in a 6-fold up-regulation of endogenous YB-1 in the nuclear
      compartment, which occurred within 90min. In accord with these findings nuclear
      fluorescence was detected with a YFP-YB-1-CFP fusion protein introduced in HepG2
      cells. In addition to DNA binding studies with endotoxemic rat liver tissue, ChIP
      assays revealed an IL-1beta-dependent increase of YB-1 binding to the Mrp2
      promoter in FAO cells. CONCLUSION: YB-1 is activated during the hepatic acute
      phase response. IL-1beta promotes a rapid nuclear YB-1 protein shuttling in
      hepatoma cells within 90 min and a transcriptional induction thereafter. This
      biphasic response may explain the IL-1beta-mediated suppression of Mrp2
      expression in endotoxemic rats.

PMID- 22361281
TI  - Genomic organization, promoter activity of grass carp MDA5 and the association of
      its polymorphisms with susceptibility/resistance to grass carp reovirus.
AB  - MDA5 (melanoma-differentiation-associated gene 5), a member of the RLR (retinoic
      acid-inducible gene I-like receptor) family, plays a pivotal role in innate
      immunity against viral infection. In the present study, the organization of grass
      carp (Ctenopharyngodon idella) MDA5 (CiMDA5) gene sequence was elucidated and
      promoter activity of its 5'-flanking region was detected. In addition, single
      nucleotide polymorphisms (SNPs) were investigated to explore their association
      with susceptibility/resistance to grass carp reovirus (GCRV). The CiMDA5 genomic
      sequence is composed of 10,906 bp, containing seven exons and six introns, which
      is distinct from its counterparts with numbers of exons. The 5'-flanking region
      of CiMDA5 gene, containing several putative transcription factor binding sites,
      was amplified using genome walking technique, exhibiting promoter activity. Six
      SNPs were discovered in the complete sequence of CiMDA5. Five of them locate in
      introns and one in 5'-flanking region. The genotype and allele distribution were
      examined by PCR-RFLP in susceptible and resistant fish. The results indicate that
      genotypes at the -713 C/G and 3338 A/C loci were significantly associated with
      the resistance to GCRV (P<0.05). Furthermore, at -713 C/G site, no CC genotype
      individual was found; the mortality in GG genotype group was 42.65%, which was
      significantly lower than that in CG genotype group (73.91%) (P<0.05). The
      mortality in CC (33.33%) genotype at 3338 A/C locus was significantly lower than
      that in AA and AC genotype (61.54%, 45.95% respectively) (P<0.05). The data
      demonstrate that -713 G and 3338 C carrier are resistant to GCRV. These results
      provide potential markers for further investigation of selective breeding of
      resistant grass carp to GCRV.

PMID- 22361282
TI  - Updates in Medical Dermatology. Introduction.

PMID- 22361283
TI  - What you and your patients need to know about vitamin D.
AB  - "Vitamin D" is the term commonly used to denote the lipid-soluble hormone
      critical for calcium homeostasis and skeletal maintenance. A precursor to the
      active compound is found in many plants and animal tissues and can be absorbed
      from the gut; it can also be derived from cell membranes in the epidermis during
      ultraviolet B irradiation. This compound is then hydroxylated sequentially in the
      liver and kidney to produce the active hormone 1,25(OH)(2)D that binds its
      nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases
      and the nuclear receptor have been identified in many tissues, suggesting
      previously unrecognized roles for vitamin D. Some epidemiologic studies have also
      correlated low levels of the inactive storage form 25(OH)D with an increased
      incidence or prevalence of a variety of diseases, suggesting that large oral
      supplements and/or increased ultraviolet (UV) exposure might therefore improve
      individual health. However, randomized, prospective controlled trials comparing
      vitamin D supplements with placebo have not supported this belief. Moreover,
      current evidence supports the conclusion that protection from UV radiation does
      not compromise vitamin D status or lead to iatrogenic disease. In contrast, high
      vitamin D levels appear to incur a risk of kidney stones and other adverse
      effects. In the case of true vitamin D deficiency, supplements are a more
      reliable and quantifiable source of the vitamin than UV exposure.

PMID- 22361284
TI  - Vitamin a: history, current uses, and controversies.
AB  - Vitamin A is required for the proper functioning of many important metabolic and
      physiologic activities, including vision, gene transcription, the immune system
      and skin cell differentiation. Both excessive and deficient levels of vitamin A
      lead to poor functioning of many human systems. The biologically active form,
      retinoic acid, binds to nuclear receptors that facilitate transcription that
      ultimately leads to it's physiological effects. Retinoids are derivatives of
      vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis
      (and other disorders of keratinization), skin cancer prevention as well as
      several bone marrow derived neoplasias. Systemic retinoids are teratogenic and
      have to be prescribed with caution and close oversight. Other potential adverse
      events are controversial. These include the relationship of retinoid derivatives
      in sunscreens, their effects on bone mineral density, depression and suicidal
      ideation and inflammatory bowel disease. These controversies will be discussed in
      detail.

PMID- 22361285
TI  - Advances in management of atopic dermatitis: new therapies and novel uses of
      existing treatments.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin condition marked by
      intensely pruritic, eczematous changes. First-line therapy includes topical
      corticosteroids during an exacerbation and long-term emollient use, followed by
      topical calcineurin inhibitors, phototherapy, and systemic therapy in more
      difficult cases. The need for more effective AD therapies with safer side effect
      profiles has pushed researchers to devise new therapies and to recycle
      traditional treatments for use in a novel manner. Innovative therapies include
      barrier therapy, novel antistaphylococcal treatments, new immunomodulatory
      agents, unconventional antipruritic agents, exclusionary diets, and probiotics.
      Advancements in these options have paved the way for a targeted approach to AD
      therapy. We will review the latest clinical research exploring these cutting-edge
      AD treatment modalities and discuss forward-thinking therapy strategies that use
      conventional AD medications in a novel manner.

PMID- 22361286
TI  - Menus for managing patients with cutaneous T-cell lymphoma.
AB  - In the management of patients with cutaneous T-cell lymphoma (CTCL), there are
      numerous distinct therapy options. Each of these therapies is discussed in terms
      of when to use it, what factors limit the success of the treatment, and what to
      expect. A menu is defined as a list of items from which to choose. The treatments
      for CTCL are presented in various menus where they are options for a particular
      goal in a particular setting of CTCL. The best recognized clinical scenarios of
      CTCL are those recognized by the staging system: limited patch plaque (T1),
      disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of
      the disease will have the menu of therapy options presented for a given goal of
      management.

PMID- 22361287
TI  - Wound healing update.
AB  - The management of acute and chronic wounds has drastically changed within the
      past 20 years. This update focuses on the most recent recommendations for acute
      wound care as well as new technologies that are available for chronic wounds.

PMID- 22361288
TI  - Update and clinical use of imaging technologies for pigmented lesions of the
      skin.
AB  - The incidence of melanoma is on the rise, and early detection of disease is
      imperative to reduce mortality. Dermatologists are key players in the early
      detection of melanoma; however, some clinicians rely on their clinical
      examination without any additional diagnostic tools to make this important
      diagnosis. Certain patients, such as atypical nevus patients, have more
      complicated mole examinations, making the diagnosis of melanoma difficult,
      whereas some melanomas, such as amelanotic melanomas, can be diagnostically
      challenging. The goal of the clinician is to detect melanoma with the highest
      accuracy, while avoiding unnecessary biopsies. Using diagnostic melanoma tools as
      an adjunct to the clinical examination, dermatologists have the opportunity to
      increase both their sensitivity and specificity for melanoma detection. This
      article will review current imaging technologies and those in development for
      pigmented lesions, updating the clinician on basic principals of such modalities
      and clinical use of such technologies in practice.

PMID- 22361289
TI  - Malignant melanoma: advances in diagnosis, prognosis, and treatment.
AB  - The detection of cutaneous melanoma still largely relies on clinical suspicion,
      skin biopsy, and histopathologic evaluation. New technologies are being evaluated
      to bypass the skin biopsy in the detection of melanoma. The quest for reliable
      biomarkers, with respect to subclinical detection, prognosis, and predicting
      treatment response, is longstanding and ongoing. New therapies have been
      developed for metastatic disease, including targeted small molecule inhibitors as
      well as immune modulators.

PMID- 22361290
TI  - Heavy metal pollution in sediments of a typical mariculture zone in South China.
AB  - The heavy metal inventory and the ecological risk of the estuarine sediments in
      Hailing Bay, an important maricultural zone along the southern coast of China,
      were investigated. Results show that the surface sediments were mainly polluted
      by As (2.17-20.34 mg/kg), Ni (1.37-42.50mg/kg), Cu (1.21-58.84 mg/kg) and Zn
      (11.69-219.22 mg/kg). Furthermore, the aquafarming zone was significantly more
      polluted than the non-aquafarming zone, and cluster analysis suggested additional
      sources of heavy metal input in the aquafarming zone. As, Cr, Cu, Ni, Pb and Zn
      were mainly present in the non-bioavailable residual form in the surface
      sediments, whereas Cd was predominantly in the highly mobile acid soluble and
      reducible fractions. The ecological risk of the polluted sediments stemmed mainly
      from Cd, and from As, Cu and Pb to less degrees. The highest potential risks
      occurred near the aquaculture base, indicating the need to control heavy metal
      inputs from aquafarming activities.

PMID- 22361294
TI  - Physiological variability in yearling alligators: clutch differences at rest and
      during activity.
AB  - The adult phenotype of an organism is the result of its genotype, the
      environment, and the interaction between the two. Assessing the relative
      contribution of these factors to the final adult phenotype continues to occupy
      researchers. Studies have shown clutch effects early in development but few have
      investigated the persistence of clutch effects on a longer time scale. Five
      clutches of American alligators were reared for 1 year in a common environment
      then assessed for the presence of clutch effects as they related to morphological
      and physiological characteristics. After 1 year, significant clutch effects were
      evident in all size related variables despite open access to food. Additionally,
      lung and liver masses remained different between clutches after animal mass was
      taken into account. Although clutch had no effect on resting heart rate, it
      significantly contributed to mean arterial pressure. During swimming and
      exhaustive exercise, the resulting respiratory and metabolic acidoses were
      strongly dependent on clutch. Therefore, while the environment can have
      significant influences on the American alligator from hatching to death, the
      measureable contribution of genetics to the morphology and physiology of the
      organism remains evident, even after 1 year of common rearing conditions. It
      behooves researchers to acknowledge and control for clutch effects when designing
      experiments.

PMID- 22361292
TI  - Computational analysis of functional long noncoding RNAs reveals lack of peptide
      coding capacity and parallels with 3' UTRs.
AB  - Recent transcriptome analyses have indicated that a large part of mammalian
      genomes are transcribed into long non-protein-coding RNAs (lncRNAs). However,
      only a very small fraction of them have been individually studied, and whether
      the majority of lncRNAs found in large-scale studies have a cellular role is
      debated. To gain insight into the sequence features and genomic architecture of
      the subset of lncRNAs that have been proven to be functional, we created a
      database containing studied lncRNAs manually culled from the literature along
      with a parallel database containing all annotated protein-coding human RNAs. The
      Functional lncRNA Database, which contains 204 lncRNAs and their splicing
      variants, is available at valadkhanlab.org/database. Analysis of the lncRNAs and
      their comparison to protein-coding transcripts revealed sequence features
      including paucity of introns and low GC content in lncRNAs, which could explain
      several biological characteristics of these transcripts, such as their nuclear
      localization and low expression level. The predicted ORFs in lncRNAs have poor
      start codon and ORF contexts, which would lead to activation of the nonsense
      mediated decay pathways and thus make it unlikely for most lncRNAs to code for
      even short peptides. Interestingly, our analyses revealed significant
      similarities between the lncRNAs and the 3' untranslated regions (3' UTRs) in
      protein-coding RNAs in structural features and sequence composition. The presence
      of these intriguing parallels between the lncRNAs and 3' UTRs, which constitute
      the two main components of the RNA-mediated cellular regulatory system, indicates
      that highly similar evolutionary constraints govern the function of regulatory
      RNA sequences in the cell.

PMID- 22361291
TI  - RNA-Puzzles: a CASP-like evaluation of RNA three-dimensional structure
      prediction.
AB  - We report the results of a first, collective, blind experiment in RNA three
      dimensional (3D) structure prediction, encompassing three prediction puzzles. The
      goals are to assess the leading edge of RNA structure prediction techniques;
      compare existing methods and tools; and evaluate their relative strengths,
      weaknesses, and limitations in terms of sequence length and structural
      complexity. The results should give potential users insight into the suitability
      of available methods for different applications and facilitate efforts in the RNA
      structure prediction community in ongoing efforts to improve prediction tools. We
      also report the creation of an automated evaluation pipeline to facilitate the
      analysis of future RNA structure prediction exercises.

PMID- 22361295
TI  - Individual genetic and genomic research results and the tradition of informed
      consent: exploring US review board guidance.
AB  - BACKGROUND: Genomic research is challenging the tradition of informed consent.
      Genomic researchers in the USA, Canada and parts of Europe are encouraged to use
      informed consent to address the prospect of disclosing individual research
      results (IRRs) to study participants. In the USA, no national policy exists to
      direct this use of informed consent, and it is unclear how local institutional
      review boards (IRBs) may want researchers to respond. OBJECTIVE AND METHODS: To
      explore publicly accessible IRB websites for guidance in this area, using
      summative content analysis. FINDINGS: Three types of research results were
      addressed in 45 informed consent templates and instructions from 20 IRBs based at
      centres conducting genomic research: (1) IRRs in general, (2) incidental findings
      (IFs) and (3) a broad and unspecified category of 'significant new findings'
      (SNFs). IRRs were more frequently referenced than IFs or SNFs. Most documents
      stated that access to IRRs would not be an option for research participants.
      These non-disclosure statements were found to coexist in some documents with
      statements that SNFs would be disclosed to participants if related to their
      willingness to participate in research. The median readability of template
      language on IRRs, IFs and SNFs exceeded a ninth-grade level. CONCLUSION: IRB
      guidance may downplay the possibility of IFs and contain conflicting messages on
      IRR non-disclosure and SNF disclosure. IRBs may need to clarify why separate IRR
      and SNF language should appear in the same consent document. The extent of these
      issues, nationally and internationally, needs to be determined.

PMID- 22361296
TI  - After-birth abortion: why should the baby live?
AB  - Abortion is largely accepted even for reasons that do not have anything to do
      with the fetus' health. By showing that (1) both fetuses and newborns do not have
      the same moral status as actual persons, (2) the fact that both are potential
      persons is morally irrelevant and (3) adoption is not always in the best interest
      of actual people, the authors argue that what we call 'after-birth abortion'
      (killing a newborn) should be permissible in all the cases where abortion is,
      including cases where the newborn is not disabled.

PMID- 22361297
TI  - Hippocampal volume and memory in narcoleptics with cataplexy.
AB  - BACKGROUND/OBJECTIVE: The objective of this study was to investigate the
      differences in hippocampal volume (HV) between narcoleptics and normal controls
      and determine if HV is associated with memory function in narcoleptics. Left and
      right HV and intracranial volumes (ICV) were manually measured and compared
      between two groups. METHODS: The study consisted of 36 drug-naive narcoleptics
      with cataplexy and 36 age- and sex-matched controls (mean age 29.0 years). All
      subjects underwent 1.6-mm-thick spoiled gradient recalled magnetic resonance
      imaging and took the Korean California Verbal Learning Test and the Rey Complex
      Figure Test to assess verbal and visual memory. RESULTS: The mean ICV was not
      different between groups (1599.2 cm(3) in narcoleptics vs. 1623.5 cm(3) in
      controls, p = .450). Bilateral mean HVs were significantly smaller in
      narcoleptics (left, 2907.2mm(3) in narcoleptics vs. 3092.3mm(3) in controls, p =
      0.005; right, 2990.8mm(3) in narcoleptics vs. 3184.3mm(3) in controls, p =
      0.004). Significance of HV differences between groups remained after corrections
      were made for gender, age, and ICV. In narcoleptics, bilateral HV was positively
      correlated with mean sleep and REM sleep latencies in Multiple Sleep Latency
      Tests. Absolute memory scores were not different between groups and were not
      correlated with HV in narcoleptics. CONCLUSIONS: Narcoleptics had smaller
      bilateral HVs compared to controls. HV had a significant relationship with sleep
      and REM sleep latencies. This study provides supportive evidence of the
      functional and anatomical deficits in medial temporal areas that are related to
      the severity of narcolepsy.

PMID- 22361298
TI  - NMR assignment of the absolute configuration of C-25 in furostanol steroidal
      saponins.
AB  - The chemical shifts of the geminal proton resonances of H(2)-26 (deltaa and
      deltab) are a widely used predictor of C-25 stereochemistry in furostanol
      steroidal saponins, being in general more resolved in 25S than 25R compounds.
      Unexpectedly, we found that application of this empirical rule in different
      solvents led to conflicting assignments of stereochemistry. An experimental
      survey revealed that, while the chemical shifts of H(2)-26 exhibit a dependence
      on C-25 configuration, it is less pronounced in methanol-d4 than pyridine-d5
      solvent, and thus the general rule derived for pyridine-d5 fails when NMR spectra
      are acquired in methanol-d4. We propose a modified empirical method for the
      direct assignment of C-25 stereochemistry in furostanol saponins in methanol-d4
      (Delta(ab)=0.45-0.48 ppm for 25S; Delta(ab)=0.33-0.35 ppm for 25R), and provide
      several detailed examples. In addition, the absolute configuration of compound 8,
      a steroidal saponin isolated in previous work from Ruscus colchicus, is corrected
      from 25R to 25S stereochemistry.

PMID- 22361299
TI  - Outbreak of a South West Pacific clone Panton-Valentine leucocidin-positive
      meticillin-resistant Staphylococcus aureus infection in a UK neonatal intensive
      care unit.
AB  - BACKGROUND: Panton-Valentine leucocidin-positive meticillin-resistant
      Staphylococcus aureus (PVL-MRSA) has become a globally common cause of community
      acquired infections. AIM: We report an outbreak of PVL-MRSA in a regional
      neonatal unit in the UK involving three babies and three staff members. METHODS:
      Quinolone susceptibility was helpful in identifying potential PVL-MRSA but toxin
      gene profiling and sequence-based typing were required to distinguish between two
      PVL-MRSA strains present in the unit. FINDINGS: All three symptomatic babies and
      two staff carriers, one of whom was symptomatic, were found to be carrying the
      South West Pacific (SWP) clone of PVL-MRSA (ST30). One of the staff carriers had
      recently visited the Philippines and was thought to be the source of the
      outbreak. Control was established using standard infection control procedures but
      one baby with relapsing MRSA colonization has required more than 100 days in
      isolation. CONCLUSION: This is the first reported neonatal outbreak associated
      with the SWP clone in the UK. Our study highlights the potential risk of further
      introductions of this organism by healthcare staff or patients epidemiologically
      linked with the Philippines.

PMID- 22361300
TI  - Analysis of 13 cases of venous compromise in 178 radial forearm free flaps for
      intraoral reconstruction.
AB  - The purpose of this study was to analyse the causes of venous compromise and flap
      failure in radial forearm free flap (RFFF) surgery for intraoral reconstruction.
      One hundred seventy-eight RFFF reconstructions were reviewed retrospectively for
      intraoral defects. Of the 13 flaps with venous obstruction, 9 flaps were
      salvaged, and 4 were lost, with a salvage rate of 69.2%. Eleven venous occlusions
      occurred within the first 72h. The main reasons for venous failure were
      mechanical obstruction or technical errors due to inadequate pedicle length and
      geometry, inadequate venous drainage, compression and kinking of the vein. The
      main cause of failure for oropharynx reconstruction was unrecognized vascular
      events due to the lack of reliable monitoring for buried flap. Oozing of dusky
      blood from the flap margin may be directly related to venous congestion in the
      early postoperative period and a late indication of a change in skin colour. In
      conclusion, a thorough operative plan, including carefully selected drainage vein
      for the flap and recipient vessels, adequate pedicle length and geometry, precise
      surgical technique, avoidance of haematoma, and expert monitoring of buried flaps
      may improve the success rate of RFFF transfer in intraoral reconstruction.

PMID- 22361301
TI  - Changing epidemiology of two male predominant cancers.

PMID- 22361302
TI  - Image quality of two different mobile cone beam computed tomographs for
      maxillofacial surgery.
AB  - PURPOSE: We evaluated two mobile cone beam computed tomographs (mCBCT) comparing
      image quality with respect to radiation dosage. Image quality was analyzed by
      using different scanning modes. MATERIALS AND METHODS: The skulls of three human
      cadavers were scanned by use of conventional Computed Tomography (CT) as well as
      with two mobile cone beam computed tomographs (Siemens Arcadis Orbic 3D and Ziehm
      Vision Vario 3D). Six different acquisition modes with different radiation
      dosages were used. The axial views of all scans were evaluated by five medical
      doctors regarding image quality by identifying predefined anatomical structures
      of the skull. A five-point ranking scale was used. The inter-rater reliability
      was statistically depicted by Cohen's Kappa coefficient. A Wilcoxon signed rank
      test was used to evaluate the rater's results. For evaluating the signal-to-noise
      ratio (SNR) a Catphan 600 reference body with two different inlays was used.
      RESULTS: Comparing the mCBCTs, the image quality of the Siemens Arcadis Orbic 3D
      in high-dosage mode received the best score (median: 2.27). The inter-rater
      reliability was fair (Kappa=-0.030 to 0.328). The Wilcoxon test showed
      significant (p<0.05) different median rating values in 18 out of 21 imaging
      modes. The SNR was higher (better) in the high-dosage modes. CONCLUSION: Intra
      operative 3D imaging by using mCBCT for maxillofacial surgery in low-dose mode
      acquisition is adequate in terms of signal-to-noise ratio and image quality. The
      image quality does not correlate in a linear manner with a higher radiation
      dosage. Surgeons using this technique should gather their own experience with the
      different acquisition modes.

PMID- 22361303
TI  - Febrile seizures after 2010-2011 influenza vaccine in young children, United
      States: a vaccine safety signal from the vaccine adverse event reporting system.
AB  - During the 2010-2011 influenza season, the Centers for Disease Control and
      Prevention and the Food and Drug Administration conducted enhanced vaccine safety
      monitoring for possible febrile seizures in all trivalent influenza vaccine (TIV)
      products in the United States using the Vaccine Adverse Event Reporting System
      (VAERS). We used Empirical Bayesian data mining techniques to assess
      disproportionate reporting after TIV and reviewed febrile seizure reports in
      children aged <5 years. On November 23, 2010, the combination of the coding term
      "febrile convulsion" and the Fluzone((r)) TIV product exceeded a predetermined
      threshold in the VAERS database. By December 10, we confirmed 43 reports of
      febrile seizure following TIV in children aged 6-23 months. Clinical features of
      most reports were consistent with typical uncomplicated febrile seizures, and all
      children recovered. Further epidemiologic assessment of a possible association
      between TIV and febrile seizures was undertaken in a separate, population-based
      vaccine safety monitoring system.

PMID- 22361304
TI  - Signal identification and evaluation for risk of febrile seizures in children
      following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink
      Project, 2010-2011.
AB  - In fall 2010 in the southern hemisphere, an increased risk of febrile seizures
      was noted in young children in Australia in the 24 h after receipt of trivalent
      inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although
      the CSL TIV vaccine was not recommended for use in young children in the US,
      during the 2010-2011 influenza season near real-time surveillance was conducted
      for febrile seizures in the 0-1 days following first dose TIV in a cohort of
      206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety
      Datalink Project. On a weekly basis, surveillance was conducted with the primary
      approach of a self-controlled risk interval design and the secondary approach of
      a current vs. historical vaccinee design. Sequential statistical methods were
      employed to account for repeated analyses of accumulating data. Signals for
      seizures based on computerized data were identified in mid November 2010 using a
      current vs. historical design and in late December 2010 using a self-controlled
      risk interval design. Further signal evaluation was conducted with chart
      confirmed febrile seizure cases using only data from the primary approach (i.e.
      self-controlled risk interval design). The magnitude of the incidence rate ratio
      and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days
      following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate
      vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio
      (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the
      IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for
      concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates
      varied by age due to the varying baseline risk for seizures in young children,
      with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV
      without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant
      TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest
      estimates occurring at 59 months (1.1 per 100,000 doses for TIV without
      concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and
      4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and
      risk difference estimates were lower for children receiving TIV without
      concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of
      preventing influenza and pneumococcal infections and associated complications,
      our findings should be placed in a benefit-risk framework to ensure that
      population health benefits are maximized.

PMID- 22361305
TI  - In the heat of a signal: responding to a vaccine safety signal for febrile
      seizures after 2010-11 influenza vaccine in young children, United States.

PMID- 22361306
TI  - Current knowledge on pancreaticobiliary reflux in normal pancreaticobiliary
      junction.
AB  - Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and
      their pathologic implications has experienced tremendous progress during the last
      few years. This article reviews the current knowledge on this condition and its
      pathological implications on gallbladder diseases. Many publications with
      different levels of evidence were found supporting biliary carcinogenesis
      associated with pancreaticobiliary reflux in normal and abnormal
      pancreaticobiliary junction. Also, there are many publications supporting the
      common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary
      junction, and sphincter of Oddi dysfunction as the most plausible cause of this
      condition. Although an important body of research has been published regarding
      pancreaticobiliary reflux in normal pancreaticobiliary junction and their
      clinical significance, the current evidence does not fully support what has been
      suggested. The reflux of pancreatic enzymes into the bile tract and gallbladder
      is a fascinating subject of study which is open to active research. The final
      demonstration of the pathophysiology and consequences of PBR in NPBL and support
      by evidence level type I would constitute a major breakthrough in the
      understanding and eventually in the treatment of gallbladder diseases.

PMID- 22361307
TI  - Neutrophil lymphocyte ratio in outcome prediction after emergency abdominal
      surgery in the elderly.
AB  - INTRODUCTION: Accurate prediction of outcome after emergency surgery in elderly
      patients may assist decision-making. Many scoring systems require post-operative
      data (e.g. P-POSSUM) whilst others have failed to gain widespread use. Recent
      reports suggest that C-reactive protein (CRP) and the neutrophil lymphocyte (N/L
      ratio) ratio may predict surgical outcome. METHODS: A retrospective review of all
      patients aged 80 years or over undergoing emergency abdominal surgery over a 22
      month period was conducted. Outcome and clinical data were collected. Univariate,
      multivariate and recursive analyses were performed for outcome at 30 days, 6
      months and 12 months. Findings were validated in a second independent dataset.
      RESULTS: 88 patients were included in the test dataset, median age 84 years. 30
      day mortality was 31%, 6-month mortality 43% and 12-month mortality 50%.
      Univariate analysis identified N/L ratio, CRP, midline laparotomy, and surgical
      risk score to predict outcome at each time point. Recursive analysis showed, N/L
      ratio >=22 best predicted 30-day outcome (p=0.0018). Multivariate analysis
      identified N/L ratio to be an independent predictor of 30-day outcome (p=0.004)
      yet CRP did not predict outcome at any time point. An independent dataset (n=84)
      confirmed N/L ratio to be a prognostic factor at 30 days (p=0.001), 6 months
      (p<0.001) and 12 months (p=0.001). CONCLUSION: N/L ratio is an easily calculable
      pre-operative measure that may have utility in the prediction of outcome after
      emergency abdominal surgery in the elderly. Further work to validate this measure
      in a larger, prospective setting and determine the underlying mechanisms that
      mediate outcome are necessary.

PMID- 22361308
TI  - Gastrocolic fistulae; From Haller till nowadays.
AB  - Gastrocolic Fistula is, in the majority of cases the pathological communication
      between stomach and transverse colon, because cases involved with the small
      intestine, pancreas and skin have been also documented, even though are rare. It
      occurs mostly in adults, but they can be present to infants, as well, as a result
      of congenital abnormalities or iatrogenic procedures (i.e. migration of PEG tube
      that placed before). In the Western Countries, the most common cause is the
      adenocarcinoma of the colon, while in Japan, adenocarcinoma of the stomach is the
      most frequent cause. It seldom appears, as a complication of a benign peptic
      ulcer, in Crohn's disease and as a result of significant intake of steroids or
      NSAIDs. The typical symptoms of a gastrocolic fistula are abdominal pain, nausea
      vomiting, diarrhea and weight loss. Radiology has been used for the detection of
      the fistulae all these years but the golden standard remained the barium enema.
      Barium meal and CT findings play a smaller role in the diagnosis. Although the
      management of gastrocolic fistulae has historically been surgical, medical
      treatment has recently been recommended as the first line when a malignancy can
      be excluded.

PMID- 22361309
TI  - Checklists: Are really necessary in the routinely clinical practice?

PMID- 22361310
TI  - The effect of low level laser on condylar growth during mandibular advancement in
      rabbits.
AB  - INTRODUCTION: It has been shown that Low Level Laser (LLL) has a positive effect
      on bone formation. The aim of this study was to evaluate the effect of low level
      laser on condylar growth during mandibular advancement in rabbits. MATERIALS AND
      METHODS: Continuous forward mandibular advancement was performed in fourteen male
      Albino rabbits with the mean age of 8 weeks and the mean weight of 1.5 +/- 0.5
      kg, with acrylic inclined planes. The rabbits were randomly assigned into two
      groups after 4 weeks. LLL (KLO3: wave length 630 nm) was irradiated at 3 points
      around the TMJ, through the skin in the first group. The exposure was performed
      for 3 minutes at each point (a total of 9 minutes) once a day for 3 weeks. The
      control group was not exposed to any irradiation. The rabbits in both groups were
      sacrificed after two months and the histological evaluation of TMJ was performed
      to compare fibrous tissue, cartilage, and new bone formation in condylar region
      in both groups. Disc displacement was also detected in both groups. Student's t
      test, Exact Fisher and Chi square tests were used for the statistical analysis.
      RESULTS: The formation of fibrous tissue was significantly lower, while bone
      formation was significantly greater in lased group as compared with control
      group. The thickness of cartilage did not differ significantly between two
      groups. CONCLUSION: Irradiation of LLL (KLO3) during mandibular advancement in
      rabbits, increases bone formation in condylar region, while neither increase in
      the cartilage thickness nor fibrous tissues was observed.

PMID- 22361311
TI  - Early experience with the femtosecond laser for cataract surgery.
AB  - OBJECTIVE: To describe the intraoperative complications and to evaluate the
      learning curve with femtosecond laser cataract surgery. DESIGN: Prospective,
      consecutive cohort study. PARTICIPANTS: The first 200 eyes undergoing femtosecond
      laser cataract surgery and refractive lens exchange in a single center. METHODS:
      The initial 200 eyes undergoing cataract surgery between April 2011 and June 2011
      by 6 surgeons were included in the study. The cases underwent anterior
      capsulotomy, lens fragmentation, and corneal incisions with the femtosecond
      laser. The procedure was completed by phacoemulsification and insertion of an
      intraocular lens. Data were collected about patient demographics, preoperative
      investigations and intraoperative complications. The cases were divided into 4
      groups-group 1 included the first 50 cases, group 2 included cases 51 through
      100, group 3 included cases 101 through 150, and group 4 included cases 151
      through 200-and were analyzed. MAIN OUTCOME MEASURES: Intraoperative complication
      rates. RESULTS: The mean age of patients included was 69.2+/-9.8 years. Of the
      200 eyes, 74.5% underwent a complete procedure of laser capsulotomy, lens
      fragmentation, and corneal incisions. Five eyes had suction breaks during the
      laser procedure that led to the remainder of the laser procedure being aborted.
      Twenty-one (10.5%) eyes showed the presence of small anterior capsular tags. The
      number of eyes with free-floating capsulotomies was 35 (17.5%). The other
      complications during the study were anterior radial tears (n = 8; 4%), posterior
      capsular ruptures (n = 7; 3.5%), and dropped nucleus (n = 4; 2%). A significant
      difference was noted among the sequential groups with respect to the number of
      docking attempts (P<0.001), miosis after the laser procedure (P<0.001), and free
      floating capsulotomies (P<0.001), suggesting an improving learning curve. The
      surgeons with prior experience with femtosecond lasers had fewer complications in
      the first 100 cases (P<0.001). No difference in complications was observed after
      the initial 100 cases. CONCLUSIONS: In this case series, there was a clear
      learning curve associated with the use of femtosecond lasers for cataract
      surgery. Adjustment to surgical technique and prior experience with a femtosecond
      laser seemed to flatten the learning curve.

PMID- 22361312
TI  - Monitoring the inflammatory process in herpetic stromal keratitis: the role of in
      vivo confocal microscopy.
AB  - PURPOSE: To investigate the role of in vivo confocal microscopy (IVCM) in the
      detection of inflammatory activity and follow-up of herpetic stromal keratitis
      (HSK). DESIGN: Prospective observational cohort study. PARTICIPANTS: Thirty-eight
      patients with active HSK. METHODS: Within 7 days after diagnosis of active HSK,
      both eyes of each patient were examined by slit-lamp biomicroscopy and white
      light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). The HSK-affected
      eyes were followed up at 1, 3, 6, and 12 months, whereas the unaffected fellow
      eyes were reexamined after 12 months. Three patients did not complete follow-up
      and were excluded for data analyses. All IVCM examinations were assessed for
      morphologic alterations characteristic of inflammatory activity and for corneal
      backscatter. As secondary outcome parameters, best-corrected visual activity
      (BCVA), central corneal thickness (CCT), intraocular pressure (IOP), and
      endothelial cell density (ECD) were determined at each study visit. We used
      repeated-measures analysis of variance to assess changes during the 12-month
      follow-up period and paired t tests to compare HSK-affected eyes with fellow
      eyes. MAIN OUTCOME MEASURES: Presence of dendriform cells, pseudoguttae, and
      keratic precipitates, and follow-up of mean corneal backscatter. RESULTS: An
      increase of dendriform cells and pseudoguttae often accompanied stromal
      infiltration. Because these IVCM parameters were indiscernible or overlooked at
      slit-lamp examination, they proved to be excellent indicators of inflammatory
      activity. At 12 months' follow-up, mean corneal backscatter had decreased
      significantly by 36%, but still fell outside the normal range in 24 (69%) of the
      HSK-affected eyes. By using slit-lamp in conjunction with IVCM, we detected 17
      recurrences in 14 of 35 patients (40%). Three of these recurrences were missed by
      slit-lamp, and 6 of these were missed by IVCM. At 12 months' follow-up, BCVA (-9
      letters), CCT (-36 MUm), and ECD (-313 cells/mm(2)) were significantly lower,
      whereas IOP (1.8 mmHg) was significantly higher, in HSK-affected eyes compared
      with fellow eyes. CONCLUSIONS: The data presented demonstrate that IVCM is
      complementary to slit-lamp examination in the follow-up of HSK, particularly
      because of its power to detect early signs of intracorneal inflammatory activity.
      Therapy guidance based on morphologic assessment and corneal backscatter
      measurement by combined IVCM and slit-lamp examination may improve the outcome of
      HSK. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial
      interest in any materials discussed in this article.

PMID- 22361313
TI  - Prevalence of primary angle closure and primary angle-closure glaucoma in a
      southwestern rural population of Japan: the Kumejima Study.
AB  - PURPOSE: To determine the prevalence and ocular biometry of primary angle closure
      (PAC) and primary angle-closure glaucoma (PACG) in a rural population in
      southwestern Japan. DESIGN: Population-based cross-sectional study. PARTICIPANTS:
      All residents aged 40 years or older in Kumejima, Okinawa, Japan. INTERVENTION:
      Of the 4632 residents 40 years of age or older, 3762 (participation rate, 81.2%)
      underwent a detailed ocular examination, including measurement of the best
      corrected visual acuity, slit-lamp examination, Goldmann applanation tonometry,
      static and dynamic gonioscopy, undilated stereoscopic optic fundus photographs,
      autorefractometry, partial coherence laser interferometry, noncontact specular
      microscopy, and screening visual field (VF) testing using frequency-doubling
      technology. If glaucoma or related or other ocular disorders were suspected, the
      subject was referred for a definitive examination including VF testing with the
      24-2 Swedish Interactive Thresholding Algorithm Standard program of the Humphrey
      Field Analyzer (Carl Zeiss Meditec, Dublin, CA). MAIN OUTCOME MEASURES:
      Prevalence rates of primary angle-closure suspects (PACS), PAC, PACG, and PACG
      suspects. RESULTS: Under the standard definitions of the International Society of
      Geographical and Epidemiological Ophthalmology, the prevalence rates of PACS,
      PAC, and PACG were 8.8%, 3.7%, and 2.0%. Extending the diagnosis of PAC and PACG
      to include people with narrow but open angles and primary peripheral anterior
      synechiae, the prevalence rates of PAC and PACG increased to 6.0% and 2.2%,
      respectively. Hence, broadening the diagnostic categories in PAC and PACG
      increased the prevalence rates by 62% and 10%. Twenty-three subjects (0.6%; 95%
      confidence interval, 0.4%-0.9%) had a history of or were diagnosed with acute
      PAC. Older age, female gender, hyperopic refractive error, short axial length,
      and shallow anterior chamber depth were independent predictors of an occludable
      angle. CONCLUSIONS: The prevalence of PACG in Kumejima (2.2%) was one of the
      highest reported in population-based studies, that is, 3.7 times higher than in
      the Tajimi Study carried out in an urban center located in the central area of
      the main island of Japan. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 22361314
TI  - The ocular pulse amplitude as a noninvasive parameter for carotid artery stenosis
      screening: a test accuracy study.
AB  - PURPOSE: To investigate a potential correlation between the ocular pulse
      amplitude (OPA; i.e., the intraocular pressure difference between the systolic
      and diastolic phases of the heartbeat) and the severity of carotid artery
      stenosis (CAS) and to test its role as a screening parameter for CAS during
      routine ophthalmic examination. DESIGN: Test accuracy study. PARTICIPANTS:
      Patients referred for color duplex ultrasound examination of the extra- and
      intracranial cerebral arteries were enrolled consecutively. METHODS: We measured
      OPA on both eyes by dynamic contour tonometry. Multivariate analyses were
      performed with risk factors for CAS (age, total cholesterol, low-density
      lipoprotein, and triglycerides) to compare the diagnostic value of OPA
      measurements with other non- or minimally invasive screening parameters. MAIN
      OUTCOME MEASURES: The difference between OPA measurements in patients with no
      (<50%) and patients with severe CAS (>70%) as well as the value of OPA
      measurements to predict the severity of CAS taking further risk factors of CAS
      into consideration. RESULTS: One hundred thirty-four eyes of 67 patients (25
      women, 42 men) with a mean age of 67+/-13 years (range, 25-87) were included. The
      means of the OPA values of those patients showing no CAS (<50%) differed
      significantly (P = 0.036) from those with a stenosis of >=70%. The multivariate
      model produced a statistically significant odds ratio (0.46; P = 0.007) for CAS
      of >=70%. CONCLUSIONS: The results of the present study provide proof of
      principle that the OPA is reduced in patients with CAS and may be used as a
      noninvasive, inexpensive, readily available, and unconfounded screening parameter
      to detect CAS and possibly to reduce the incidence of stroke. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 22361315
TI  - Giant ocular surface squamous neoplasia managed with interferon alpha-2b as
      immunotherapy or immunoreduction.
AB  - OBJECTIVE: To evaluate the efficacy of interferon alpha-2b (IFNalpha2b) for
      extensive ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective,
      interventional case series. PARTICIPANTS: Eighteen eyes in 18 patients. METHODS:
      Each patient with giant OSSN (a single tumor >=15 mm basal diameter or >=6 limbal
      clock-hours) was managed with topical IFNalpha2b (1 million IU/ml) 4 times daily
      or with injection IFNalpha2b (a portion of 10 million IU/ml vial) with follow-up
      every 1 to 3 months. MAIN OUTCOME MEASURES: Tumor response, recurrence, and
      treatment complications were evaluated. RESULTS: Eighteen patients with giant
      OSSN (median diameter [MD], 20 mm; median clock-hours [MCH], 6) were treated with
      topical IFNalpha2b (n = 12), injection IFNalpha2b (n = 3), or both (n = 3). The
      IFNalpha2b achieved complete tumor control (immunotherapy) in 13 eyes and partial
      tumor control with reduction in size (immunoreduction) in 5 eyes. Topical
      IFNalpha2b alone (n = 12) provided complete immunotherapy in 7 eyes (MD, 12 mm;
      MCH, 9) over a median period of 5 months and immunoreduction by 74% in 5 eyes
      (MD, 20 mm; MCH, 3), allowing for subsequent surgical excision (n = 3),
      photodynamic therapy (n = 1), or cryotherapy (n = 1) for tumor control. Injection
      IFNalpha2b alone (n = 3; median, 1 injection) provided complete control of giant
      tarsal conjunctival OSSN (MD, 20 mm) over a 1-month period. A combination of
      topical and injection IFNalpha2b (n = 3; median, 3 injections) completely
      resolved larger tumors (MD, 30 mm; MCH, 6) over a 6-month period. Complications
      of IFNalpha2b included transient flu-like symptoms (n = 3), corneal epithelial
      defect (n = 2), and conjunctival hyperemia (n = 1). During a median follow-up of
      11 months, there were no tumor recurrences, but 2 new tumors appeared at a remote
      site from the original tumor, requiring operative intervention. CONCLUSIONS: In
      72% of giant OSSNs IFNalpha2b achieved complete control (immunotherapy); there
      was a reduction in size (immunoreduction) in 28% of giant OSSNs.

PMID- 22361316
TI  - Risk factors for the development of retroprosthetic membranes with Boston
      keratoprosthesis type 1: multicenter study results.
AB  - OBJECTIVE: The purpose of this study was to identify possible risk factors for
      retroprosthetic membrane (RPM) development in a large, multicenter cohort of
      patients receiving a Boston type 1 keratoprosthesis. DESIGN: Cohort study.
      PARTICIPANTS: The final analysis included 265 eyes of 265 patients who underwent
      implantation of a Boston keratoprosthesis type I device between January 2003 and
      July 2008 by 1 of 19 surgeons at 18 medical centers. METHODS: Forms reporting
      preoperative, intraoperative, and postoperative parameters were prospectively
      collected and subsequently analyzed at a central data collection site. MAIN
      OUTCOME MEASURES: The primary outcome was the presence or absence of an RPM
      during the follow-up period. RESULTS: The average age of patients was 63.3+/-19.1
      years, 48.5% of the patients were female, and 52.5% of procedures were performed
      on the right eye. The mean follow-up time was 17.8+/-14.9 months. The majority
      (85.4%; n = 222) had undergone an average of 2.2+/-1.2 (range, 1-8) penetrating
      keratoplasties before keratoprosthesis implantation, and 38 eyes (14.6%) received
      a primary keratoprosthesis. The overall RPM formation rate was 31.7% (n = 84).
      The most significant risk factor for RPM development was infectious keratitis (as
      a surgical indication for keratoprosthesis surgery itself), resulting in a rate
      of RPM formation of 70.6%. As an independent risk factor, the hazard ratio (HR)
      of RPM development in these eyes was 3.20 (95% confidence interval, 1.66-6.17).
      Aniridia was also an independent risk factor for RPM development (HR, 3.13; 95%
      confidence interval, 1.10-8.89). CONCLUSIONS: Formation of RPM is a common
      complication of keratoprosthesis surgery, occurring in approximately one-third of
      cases. Eyes at the highest risk of RPM development are those receiving corneal
      replacement for infectious keratitis and aniridia.

PMID- 22361317
TI  - Comparison between aniridia with and without PAX6 mutations: clinical and
      molecular analysis in 14 Korean patients with aniridia.
AB  - PURPOSE: To describe clinical and molecular characteristics of Korean patients
      with aniridia and to compare the clinical phenotype between those having an
      identifiable PAX6 mutation and those not. DESIGN: Comparative case series.
      PARTICIPANTS: A total of 14 Korean patients from 10 families with aniridia.
      METHODS: Complete ophthalmologic examinations were performed for all patients.
      PAX6 analysis included direct sequencing of all coding regions and multiplex
      ligation-dependent probe amplification (MLPA) to detect large deletions when the
      sequencing was negative. If the PAX6 analysis failed to reveal any identifiable
      mutations, genomic copy number variation analysis via array comparative genomic
      hybridization (CGH) and candidate gene PITX3 and FOXE3 sequencing were then
      performed. MAIN OUTCOME MEASURES: Severity of ocular abnormalities and genetic
      findings. RESULTS: Sequencing of PAX6 exhibited 5 different heterozygous
      mutations in 8 patients from 5 families; 2 (p.Ser43Phe, IVS8-9C>G) were novel,
      and 3 (p.Arg208Trp, p.Arg317X, and p.X423L) have been previously reported. Among
      the remaining 6 patients in whom the PAX6 sequencing was negative, MLPA
      identified large deletions in 2 sporadic patients. However, the array CGH and
      candidate gene sequencing found no genomic or genetic abnormalities. The mutation
      detection rate was therefore 70%. Patients harboring an identifiable mutation in
      PAX6 had either a severe or a mild variant phenotype depending on the type of
      mutations. Likewise, among patients without an identifiable PAX6 mutation, their
      phenotypes varied widely from severe to very mild. CONCLUSIONS: This study adds 2
      novel PAX6 mutations to those previously reported, providing further evidence for
      genetic and phenotypic heterogeneity in aniridic ocular malformation. There was
      no difference in the clinical phenotype between patients with and without
      detectable mutations in the PAX6 gene. The wide variability of ocular phenotype
      regardless of the presence or absence of PAX6 mutations calls for a further
      appreciation of the complexity in the molecular diagnosis of aniridia and
      suggests that this ocular malformation may be better regarded as a group of
      heterogeneous disorders, rather than a single disease entity, associated with
      mutations in PAX6 and/or other genes located elsewhere in the human genome.
      FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest
      in any of the materials discussed in this article.

PMID- 22361318
TI  - Effect of the duration of macular edema on clinical outcomes in retinal vein
      occlusion treated with dexamethasone intravitreal implant.
AB  - PURPOSE: To assess the effect of duration of macular edema (ME) on clinical
      outcomes after treatment with dexamethasone intravitreal implant 0.7 mg (Ozurdex;
      Allergan, Inc, Irvine, CA) in patients with ME following branch retinal vein
      occlusion (BRVO) or central retinal vein occlusion (CRVO). DESIGN: Post hoc
      analysis of pooled data from 2 randomized, controlled trials. PARTICIPANTS:
      Patients with vision loss resulting from ME of 6 weeks' duration or more after
      BRVO or CRVO (n = 690). METHODS: The relationship between ME duration at the time
      of first treatment and treatment outcomes was assessed using logistic regression.
      Other factors potentially associated with ME duration or patient outcomes were
      adjusted for in the analyses. MAIN OUTCOME MEASURES: The proportion of patients
      achieving at least 15 letters improvement in best-corrected visual acuity (BCVA)
      or at least 200-MUm or more reduction in central retinal thickness 6 or 12 months
      after the first treatment with dexamethasone intravitreal implant 0.7 mg.
      RESULTS: In the 6-month analysis, each 1-month increase in ME duration was
      associated with a significantly lower likelihood of achieving a BCVA improvement
      of 15 letters or more (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.83
      0.94; P<0.001) or a CRT reduction of 200-MUm or more (OR, 0.91; 95% CI, 0.86
      0.97; P<0.01) 6 months after treatment. In the 12-month analysis, increased ME
      duration was associated with a significantly lower likelihood of achieving BCVA
      improvement of 15 letters or more improvement in BCVA (OR, 0.85; 95% CI, 0.76
      0.95; P<0.01) 12 months after treatment; duration was not significantly
      associated with the likelihood of a CRT reduction of 200-MUm or more at 12
      months. In general, the effect of ME duration on outcomes was stronger and
      statistically significant in BRVO patients, but weaker and not statistically
      significant in CRVO patients. CONCLUSIONS: In eyes with retinal vein occlusion,
      longer ME duration at the time of first treatment with the dexamethasone
      intravitreal implant 0.7 mg was associated with a significantly lower likelihood
      of achieving clinically meaningful improvements in vision or CRT 6 or 12 months
      after treatment. This suggests that prompt treatment for retinal vein occlusion,
      particularly BRVO, may be associated with improved clinical outcomes. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 22361320
TI  - A comparison between the first-fit settings of two multichannel digital signal
      processing strategies: music quality ratings and speech-in-noise scores.
AB  - PURPOSE: The aim of this study was to determine which level-dependent hearing aid
      digital signal-processing strategy (DSP) participants preferred when listening to
      music and/or performing a speech-in-noise task. METHOD: Two receiver-in-the-ear
      hearing aids were compared: one using 32-channel adaptive dynamic range
      optimization (ADRO) and the other wide dynamic range compression (WDRC)
      incorporating dual fast (4 channel) and slow (15 channel) processing. The
      manufacturers' first-fit settings based on participants' audiograms were used in
      both cases. Results were obtained from 18 participants on a quick speech-in-noise
      (QuickSIN; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) task and for 3
      music listening conditions (classical, jazz, and rock). RESULTS: Participants
      preferred the quality of music and performed better at the QuickSIN task using
      the hearing aids with ADRO processing. A potential reason for the better
      performance of the ADRO hearing aids was less fluctuation in output with change
      in sound dynamics. CONCLUSION: ADRO processing has advantages for both music
      quality and speech recognition in noise over the multichannel WDRC processing
      that was used in the study. Further evaluations of which DSP aspects contribute
      to listener preference are required.

PMID- 22361319
TI  - The cost effectiveness of NHS physiotherapy support for occupational health (OH)
      services.
AB  - BACKGROUND: Musculoskeletal pain is detrimental to quality of life (QOL) and
      disruptive to activities of daily living. It also places a major economic burden
      on healthcare systems and wider society. In 2006, the Welsh Assembly Government
      (WAG) established a three tiered self-referral Occupational Health Physiotherapy
      Pilot Project (OHPPP) comprising: 1.) telephone advice and triage, 2.) face-to
      face physiotherapy assessment and treatment if required, and 3.) workplace
      assessment and a return-to-work facilitation package as appropriate. This study
      aimed to evaluate the feasibility and cost-effectiveness of the pilot service.
      METHODS: A pragmatic cohort study was undertaken, with all OHPPP service users
      between September 2008 and February 2009 being invited to participate.
      Participants were assessed on clinical status, yellow flags, sickness absence and
      work performance at baseline, after treatment and at 3 month follow up. Cost
      effectiveness was evaluated from both top-down and bottom-up perspectives and
      cost per Quality Adjusted Life Year (cost/QALY) was calculated. The cost
      effectiveness analysis assessed the increase in service cost that would be
      necessary before the cost-effectiveness of the service was compromised. RESULTS:
      A total of 515 patients completed questionnaires at baseline. Of these, 486 were
      referred for face to face assessment with a physiotherapist and were included in
      the analysis for the current study. 264 (54.3%) and 199 (40.9%) were retained at
      end of treatment and 3 month follow up respectively. An improvement was observed
      at follow up in all the clinical outcomes assessed, as well as a reduction in
      healthcare resource usage and sickness absence, and improvement in self-reported
      work performance. Multivariate regression indicated that baseline and current
      physical health were associated with work-related outcomes at follow up. The
      costs of the service were L194-L360 per service user depending on the method
      used, and the health gains contributed to a cost/QALY of L1386-L7760, which would
      represent value for money according to current UK thresholds. Sensitivity
      analyses demonstrated that the service would remain cost effective until the
      service costs were increased to 160% per user. CONCLUSIONS: This pragmatic
      evaluation of the OHPPP indicated that it was likely to be feasible in terms of
      service usage and could potentially be cost effective in terms of QALYs. Further,
      the study confirmed that improving physical health status for musculoskeletal
      pain patients is important in reducing problems with work capacity and related
      costs. This study suggests that this type of service could be potentially be
      useful in reducing the burden of pain and should be further investigated, ideally
      via randomised controlled trials assessing effectiveness and cost-effectiveness.

PMID- 22361321
TI  - Immunometabolism of AMPK in insulin resistance and atherosclerosis.
AB  - Obesity leads to insulin resistance and atherosclerosis, which precede Type 2
      diabetes and cardiovascular disease. Immunometabolism addresses how metabolic and
      inflammatory pathways converge to maintain health and a contemporary problem is
      determining how obesity-induced inflammation precipitates chronic diseases such
      as insulin resistance and atherosclerosis. AMP-activated protein kinase (AMPK) is
      an important serine/threonine kinase well known for regulating metabolic
      processes and maintaining energy homeostasis. However, both metabolic and
      immunological AMPK-mediated effects play a role in disease. Pro-inflammatory
      mediators suppress AMPK activity and hinder lipid oxidation. In addition, AMPK
      activation curbs inflammation by directly inhibiting pro-inflammatory signaling
      pathways and limiting the build-up of specific lipid intermediates that elicit
      immune responses. In the context of obesity and chronic disease, these reciprocal
      responses involve both immune and metabolic cells. Therefore, the
      immunometabolism of AMPK-mediated processes and therapeutics should be considered
      in atherosclerosis and insulin resistance.

PMID- 22361322
TI  - Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk:
      an update by meta-analysis.
AB  - Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been
      implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results
      to date have been inconclusive. The aim of this study was to investigate the
      association between polymorphisms in the VDR gene and T1DM risk by meta-analysis.
      A total of 57 case-control studies in 26 published studies were included. The
      results indicated that the BsmI polymorphism is associated with increased risk of
      T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI
      polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk
      of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no
      significant association was found in other populations for other polymorphisms.
      Results from the current study suggest that the BsmI polymorphism is associated
      with increased risk of T1DM, especially in Asians. Further studies are needed to
      confirm our results.

PMID- 22361323
TI  - Identification of reproduction-related proteins and characterization of
      proteasome alpha 3 and proteasome beta 6 cDNAs in testes of the giant tiger
      shrimp Penaeus monodon.
AB  - Cellular proteomic analysis was carried out to identify reproduction-related
      proteins in testes of wild and domesticated broodstock of Penaeus monodon. In
      total, 642 protein spots were characterized and 287 spots (44.70%) significantly
      matched protein sequences in the databases (P<0.05). To examine a role of the
      proteasome system in testicular development of P. monodon, the expression
      profiles of proteasome alpha 3 subunit (PmPsma3) and proteasome beta 6 (PmPsmb6)
      mRNA in different groups of domesticated shrimp and in wild broodstock were
      examined. The expression levels of these transcripts in testes of 18-month-old
      domesticated shrimp were significantly lower than those of wild broodstock
      (P<0.05). Interestingly, the expression levels of testicular PmPsma3 and PmPsmb6
      in 18-month-old shrimp were significantly increased at 24 h following serotonin
      injection (50 MUg/g body weight). Results suggested that reduced degrees of
      maturation in captive P. monodon males may be partially resolved by exogenous 5
      HT administration.

PMID- 22361324
TI  - Endothelial cells overexpressing interleukin-8 receptors reduce inflammatory and
      neointimal responses to arterial injury.
AB  - BACKGROUND: Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes
      bind to IL8 and direct neutrophil recruitment to sites of inflammation, including
      acutely injured arteries. This study tested whether administration of IL8RA-
      and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion
      of ECs to the injured surface, thus suppressing inflammation and neointima
      formation in balloon-injured rat carotid arteries. We tested the hypothesis that
      targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents
      inflammatory responses and promotes structural recovery of arteries after
      endoluminal injury. METHODS AND RESULTS: Young adult male rats received balloon
      injury of the right carotid artery and were transfused intravenously with ECs
      (total, 1.5*10(6) cells at 1, 3, and 5 hours after injury) transduced with
      adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes,
      AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs
      inhibited proinflammatory mediators expression significantly (by 60% to 85%) and
      reduced infiltration of neutrophils and monocytes/macrophages into injured
      arteries at 1 day after injury, as well as stimulating a 2-fold increase in
      reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC
      treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28
      days after injury. CONCLUSIONS: ECs with overexpression of IL8RA and/or IL8RB
      mimic the behavior of neutrophils that target and adhere to injured tissues,
      preventing inflammation and neointima formation. Targeted delivery of ECs to
      arteries with endoluminal injury provides a novel strategy for the prevention and
      treatment of cardiovascular disease.

PMID- 22361325
TI  - Changing epidemiology of abdominal aortic aneurysms in England and Wales: older
      and more benign?
AB  - BACKGROUND: Recent studies from Australia, New Zealand, and Sweden have reported
      declines in abdominal aortic aneurysm (AAA) incidence, prevalence, and mortality.
      This finding may have important implications for screening programs. This study
      determined trends in AAA incidence and mortality in England and Wales. METHODS
      AND RESULTS: Cause-specific mortality data for England and Wales were obtained
      from UK Office for National Statistics, and hospital admissions and procedures
      data for England were obtained from Hospital Episode Statistics from 2001 to
      2009. Poisson regression models were constructed to estimate the relative change
      over time. Age-standardized rates for AAA mortality in England and Wales fell
      significantly by 35.7% from 2001 to 2009, which was largely due to a 35.3% drop
      in age-standardized ruptured AAA deaths. During the same period, ruptured AAA
      admissions and emergency AAA repairs in England declined by 29.3% and 35.5%,
      respectively. In contrast, nonruptured AAA admissions remained static, and
      nonemergency AAA repairs increased by 17.2%. The average ages for hospital
      admissions for nonruptured AAAs and ruptured AAAs increased by 0.19 years of age
      per annum (P<0.001) and 0.09 years of age per annum (P<0.001), respectively.
      Nonruptured AAA admissions increased by 21.4% in age band 75 years or more but
      declined by 11.7% in ages <75 years. CONCLUSIONS: AAA mortality, ruptured AAA
      admission, and emergency AAA repair have declined in England and Wales. However,
      nonruptured AAA admission has remained steady, with an increasing rate in older
      population offsetting a decreasing rate in younger population. This suggests a
      shift in AAA presentation to the older population. Present screening strategies
      may need reassessment to include consideration for increasing the age at which to
      screen men for AAAs.

PMID- 22361327
TI  - Of mice and children: lessons from a Kawasaki mouse model.

PMID- 22361326
TI  - Interleukin-1beta is crucial for the induction of coronary artery inflammation in
      a mouse model of Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD) is the most common cause of acute vasculitis
      and acquired cardiac disease in US children. Untreated, children may develop
      coronary artery aneurysms, myocardial infarction, and sudden death as a result of
      the illness. Up to a third of KD patients fail to respond to intravenous
      immunoglobulin, the standard therapy, and alternative treatments are being
      investigated. Genetic studies have indicated a possible role for interleukin (IL)
      1beta in KD. We therefore explored the role of IL-1beta in a murine model of KD.
      METHODS AND RESULTS: Using an established mouse model of KD that involves
      injection of Lactobacillus casei cell wall extract (LCWE), we investigated the
      role of IL-1beta and caspase-1 (activated by the inflammasome and required for IL
      1beta maturation) in coronary arteritis and evaluated the efficacy of IL-1
      receptor antagonist as a potential treatment. LCWE-induced IL-1beta maturation
      and secretion were dependent on the NLRP3 inflammasome in macrophages. Both
      caspase-1-deficient and IL-1 receptor-deficient mice were protected from LCWE
      induced coronary lesions. Injection of recombinant IL-1beta into caspase-1
      deficient mice restored the ability of LCWE to cause coronary lesions in response
      to LCWE. Furthermore, daily injections of the IL-1 receptor antagonist prevented
      LCWE-mediated coronary lesions up to 3 days after LCWE injection. CONCLUSIONS:
      Our results strongly suggest that caspase-1 and IL-1beta play critical roles in
      the development of coronary lesions in this KD mouse model, blocked by IL-1
      receptor antagonist. Therefore, anti-IL-1beta treatment strategies may constitute
      an effective, more targeted treatment of KD to prevent coronary lesions.

PMID- 22361328
TI  - Predicting long-term survival for coronary artery bypass graft surgery and
      percutaneous coronary intervention: another important step forward.

PMID- 22361329
TI  - Prediction of long-term mortality after percutaneous coronary intervention in
      older adults: results from the National Cardiovascular Data Registry.
AB  - BACKGROUND: The purpose of this study was to develop a long-term model to predict
      mortality after percutaneous coronary intervention in both patients with ST
      segment elevation myocardial infarction and those with more stable coronary
      disease. METHODS AND RESULTS: The American College of Cardiology Foundation
      CathPCI Registry data were linked to the Centers for Medicare and Medicaid
      Services 100% denominator file by probabilistic matching. Preprocedure
      demographic and clinical variables from the CathPCI Registry were used to predict
      the probability of death over 3 years as recorded in the Centers for Medicare and
      Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518
      195 patients aged >=65 years undergoing first percutaneous coronary intervention
      in the CathPCI Registry were successfully linked to Centers for Medicare and
      Medicaid Services data. This study population was randomly divided into 60%
      derivation and 40% validation cohorts. Median follow-up was 15 months, with
      mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years,
      respectively. Twenty-four characteristics related to demographics, clinical
      comorbidity, prior history of disease, and indices of disease severity and acuity
      were identified as being associated with mortality. The C indices in the
      validation cohorts for patients with and without ST-segment elevation myocardial
      infarction were 0.79 and 0.78. The model calibrated well across a wide range of
      predicted probabilities. CONCLUSIONS: On the basis of the large and nationally
      representative CathPCI Registry, we have developed a model that has excellent
      discrimination, calibration, and validation to predict survival up to 3 years
      after percutaneous coronary intervention.

PMID- 22361331
TI  - [Diagnosis and treatment of lupus nephritis].

PMID- 22361330
TI  - Predictors of long-term survival after coronary artery bypass grafting surgery:
      results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the
      ASCERT study).
AB  - BACKGROUND: Most survival prediction models for coronary artery bypass grafting
      surgery are limited to in-hospital or 30-day end points. We estimate a long-term
      survival model using data from the Society of Thoracic Surgeons Adult Cardiac
      Surgery Database and Centers for Medicare and Medicaid Services. METHODS AND
      RESULTS: The final study cohort included 348 341 isolated coronary artery bypass
      grafting patients aged >=65 years, discharged between January 1, 2002, and
      December 31, 2007, from 917 Society of Thoracic Surgeons-participating hospitals,
      randomly divided into training (n=174 506) and validation (n=173 835) samples.
      Through linkage with Centers for Medicare and Medicaid Services claims data, we
      ascertained vital status from date of surgery through December 31, 2008 (1- to 6
      year follow-up). Because the proportional hazards assumption was violated, we fit
      4 Cox regression models conditional on being alive at the beginning of the
      following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2
      years. Kaplan-Meier-estimated mortality was 3.2% at 30 days, 6.4% at 180 days,
      8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for
      predicting overall survival time was 0.732. Some risk factors (eg, emergency
      status, shock, reoperation) were strong predictors of short-term outcome but, for
      early survivors, became nonsignificant within 2 years. The adverse impact of some
      other risk factors (eg, dialysis-dependent renal failure, insulin-dependent
      diabetes mellitus) continued to increase. CONCLUSIONS: Using clinical registry
      data and longitudinal claims data, we developed a long-term survival prediction
      model for isolated coronary artery bypass grafting. This provides valuable
      information for shared decision making, comparative effectiveness research,
      quality improvement, and provider profiling.

PMID- 22361332
TI  - T-cell-receptor-like antibodies - generation, function and applications.
AB  - Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in
      response, are activated to eliminate these cells. In order to be activated, the
      clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen
      presented by the membrane surface major histocompatibility complex (MHC)
      molecule. Cells that have undergone malignant transformation or viral infection
      present peptides derived from tumour-associated antigens or viral proteins on
      their MHC class I molecules. Therefore, disease-specific MHC-peptide complexes
      are desirable targets for immunotherapeutic approaches. One such approach
      transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC
      peptide complexes into high-affinity soluble antibody molecules endowed with a
      TCR-like specificity towards tumour or viral epitopes. These antibodies, termed
      TCR-like antibodies, are being developed as a new class of immunotherapeutics
      that can target tumour and virus-infected cells and mediate their specific
      killing. In addition to their therapeutic capabilities, TCR-like antibodies are
      being developed as diagnostic reagents for cancer and infectious diseases, and
      serve as valuable research tools for studying MHC class I antigen presentation.

PMID- 22361333
TI  - Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular
      diseases.
AB  - Nitric oxide synthase enzyme (NOS) possesses the unique ability to be "uncoupled"
      to produce superoxide anion (O(2)(-)) instead of nitric oxide (NO). Reduced NO
      bioavailability as a result of NOS uncoupling has been speculated to play an
      essential role in cardiovascular pathologies including dilated cardiomyopathy,
      ischemia reperfusion injury, endothelial dysfunction, atherosclerosis,
      hypertension and diabetes mellitus. NO serves many important roles in the heart
      including stimulation of adenylate cyclase (AC) at low levels or guanalyl cyclase
      (sGC) at higher levels, or by s-nitrosylation of intracellular Ca(2+) regulatory
      proteins thus altering excitation-contraction coupling. Not surprisingly, NOS
      uncoupling is an emerging therapeutic target in cardiovascular diseases.
      Restoring proper NOS activity by increasing intracellular levels of its cofactor
      tetrahydrobiopterin (BH4) is effective in the management of hypertensive
      diastolic dysfunction, ischemia-reperfusion injury, myocardial infarction and
      endothelial dysfunction. New evidence is constantly emerging highlighting the
      importance of NOS uncoupling in cardiovascular pathologies thus the purpose of
      this mini-review is to showcase the new advances and promising treatments for NOS
      uncoupling in CV disease.

PMID- 22361334
TI  - Hepatocyte growth factor stimulated angiogenesis without inflammation:
      differential actions between hepatocyte growth factor, vascular endothelial
      growth factor and basic fibroblast growth factor.
AB  - Based on the potent angiogenic effects of hepatocyte growth factor (HGF),
      therapeutic angiogenesis using human HGF plasmid DNA increased tissue perfusion
      and reduced symptoms in patients with critical limb ischemia (CLI) in randomized
      placebo-controlled clinical trials. To explore further the potent angiogenic
      activity of HGF, the present study compared the effects of HGF, vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on
      angiogenesis and vascular inflammation. All of HGF, VEGF and bFGF significantly
      induced the formation of capillary blood vessel and granulation tissue in the rat
      paper disc model as an in vivo animal model of angiogenesis. However, although
      HGF, bFGF and VEGF significantly increased the growth of vascular endothelial
      cells, bFGF alone, but not HGF or VEGF, significantly increased the growth of
      vascular smooth muscle cells (VSMCs) in the in vitro proliferation assay. In
      addition, bFGF, but not HGF or VEGF, significantly activated an essential
      transcription factor for inflammation, NFkappaB, and gene expression of its
      downstream inflammation-related cytokines (IL-8 and MCP-1) in VSMCs, accompanied
      by an increase in the vascular permeability in the rat paper disc model. Thus,
      the present results indicated that HGF induced angiogenesis without vascular
      inflammation, different from bFGF and VEGF. These different properties between
      HGF, VEGF and bFGF might affect the efficiency of therapeutic angiogenesis.

PMID- 22361335
TI  - Link between endometriosis and ovarian-cancer subtypes.

PMID- 22361337
TI  - Laparoscopic right colectomy from top to bottom.

PMID- 22361338
TI  - Plasminogen activator inhibitor-1 and angiotensin converting enzyme gene
      polymorphisms in Turkish asthmatic children.
AB  - BACKGROUND: Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and
      angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility
      to asthma. In this study, we aimed to investigate whether there was any
      association between childhood asthma and polymorphisms of the PAI-1 and ACE
      genes. METHODS: Two hundred and three Turkish children aged 5-15 years, including
      102 asthmatic patients and 101 healthy control subjects were included in this
      study. The asthma group was divided into two groups as follows: Group I:
      Asthmatic children with positive family history for atopy (n=53), Group II:
      Asthmatic children without any family history for atopy (n=49). One hundred and
      twenty-eight atopic family members were also included in the study. The
      insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene
      polymorphisms was carried out by polymerase chain reaction. RESULTS: The
      prevalence of the PAI-1 4G allele was significantly greater in asthmatic children
      compared to control group (p<0.05, OR: 1.64 (1.11-2.43)) but there was no
      significant relation between ACE I/D genotypes and childhood asthma. No
      significant difference was detected between Groups I and II in terms of these ACE
      and PAI-1 genotypes and allele frequencies. No significant relationship was found
      between both gene polymorphisms and total serum IgE and skin prick test results.
      CONCLUSION: It has been established that PAI-1 4G allele may be a genetic risk
      factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in
      the development of asthma in the sample of Turkish children.

PMID- 22361339
TI  - Reflex seizures and reflex epilepsies: old models for understanding mechanisms of
      epileptogenesis.
AB  - Reflex seizures and epilepsies represent an ancient human model to understand
      basic mechanisms of epilepsy. The increase of light stimulation makes this issue
      extremely actual and interesting. In addition, a lot of observations show the
      frequent occurrence of provoked seizures in malformations of cortical development
      and in recently defined conditions such as familial or sporadic lateral temporal
      epilepsy. Advances in morphological and functional neuroimaging techniques, and
      the possibility of their fusion with EEG (e.g., fMRI-EEG co-registration) offer a
      unique non-invasive opportunity to investigate cortical areas and brain networks
      involved in cerebral functions and in epileptic discharges.

PMID- 22361336
TI  - Association between endometriosis and risk of histological subtypes of ovarian
      cancer: a pooled analysis of case-control studies.
AB  - BACKGROUND: Endometriosis is a risk factor for epithelial ovarian cancer;
      however, whether this risk extends to all invasive histological subtypes or
      borderline tumours is not clear. We undertook an international collaborative
      study to assess the association between endometriosis and histological subtypes
      of ovarian cancer. METHODS: Data from 13 ovarian cancer case-control studies,
      which were part of the Ovarian Cancer Association Consortium, were pooled and
      logistic regression analyses were undertaken to assess the association between
      self-reported endometriosis and risk of ovarian cancer. Analyses of invasive
      cases were done with respect to histological subtypes, grade, and stage, and
      analyses of borderline tumours by histological subtype. Age, ethnic origin, study
      site, parity, and duration of oral contraceptive use were included in all
      analytical models. FINDINGS: 13 226 controls and 7911 women with invasive ovarian
      cancer were included in this analysis. 818 and 738, respectively, reported a
      history of endometriosis. 1907 women with borderline ovarian cancer were also
      included in the analysis, and 168 of these reported a history of endometriosis.
      Self-reported endometriosis was associated with a significantly increased risk of
      clear-cell (136 [20.2%] of 674 cases vs 818 [6.2%] of 13 226 controls, odds ratio
      3.05, 95% CI 2.43-3.84, p<0.0001), low-grade serous (31 [9.2%] of 336 cases,
      2.11, 1.39-3.20, p<0.0001), and endometrioid invasive ovarian cancers (169
      [13.9%] of 1220 cases, 2.04, 1.67-2.48, p<0.0001). No association was noted
      between endometriosis and risk of mucinous (31 [6.0%] of 516 cases, 1.02, 0.69
      1.50, p=0.93) or high-grade serous invasive ovarian cancer (261 [7.1%] of 3659
      cases, 1.13, 0.97-1.32, p=0.13), or borderline tumours of either subtype (serous
      103 [9.0%] of 1140 cases, 1.20, 0.95-1.52, p=0.12, and mucinous 65 [8.5%] of 767
      cases, 1.12, 0.84-1.48, p=0.45). INTERPRETATION: Clinicians should be aware of
      the increased risk of specific subtypes of ovarian cancer in women with
      endometriosis. Future efforts should focus on understanding the mechanisms that
      might lead to malignant transformation of endometriosis so as to help identify
      subsets of women at increased risk of ovarian cancer. FUNDING: Ovarian Cancer
      Research Fund, National Institutes of Health, California Cancer Research Program,
      California Department of Health Services, Lon V Smith Foundation, European
      Community's Seventh Framework Programme, German Federal Ministry of Education and
      Research of Germany, Programme of Clinical Biomedical Research, German Cancer
      Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health
      Research, National Health and Medical Research Council of Australia, US Army
      Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation
      of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance
      Foundation.

PMID- 22361340
TI  - Love me tender: an Omics window on the bovine meat tenderness network.
AB  - Meat tenderness prediction is a challenging task, especially in Maremmana, an
      Italian autochtonous and highly appreciated beef breed. In the present study we
      reported an integrated proteomics, phosphoproteomics and metabolomics overview of
      meat tenderness in longissimus dorsi from 15 male Maremmana individuals, through
      the discrimination of tender and tough groups via standard meat tenderness
      indicators (WBS, MFI(4 h), MFI(10 days), sarcomere length) and their correlation
      with results from Omics analyses. Results revealed that the tender meat group was
      characterized by higher levels of glycolytic enzymes, which were less
      phosphorylated and overall more active (lactate accumulation was higher in the
      tender group), than in tough counterparts. Additionally, we could observe a
      higher level of oxidative stress in the tender group. No proteomics nor
      phosphoproteomics result hinted at the widely accepted role of calpains and
      cathepsins, except for the indication of calcium homeostasis dysregulation.
      Nevertheless, myofibrillar degradation was monitored and related to structural
      protein fragmentations. Fragmentation of structural proteins and activities of
      glycolytic enzymes were inversely related to their phosphorylation levels,
      suggesting that PTMs might add further levels of complexity in the frame of meat
      tenderness.

PMID- 22361341
TI  - Analysis of the nuclear proteome of the resurrection plant Xerophyta viscosa in
      response to dehydration stress using iTRAQ with 2DLC and tandem mass
      spectrometry.
AB  - Xerophyta viscosa Baker (family Velloziaceae) is a desiccation tolerant plant
      which survives extremes of dehydration down to 5% relative water content (RWC)
      and resumes full physiological activity within 80h of rehydration. The nuclear
      proteome of Xerophyta viscosa and its response to dehydration at 35% RWC as
      compared to fully hydrated plants was analysed using iTRAQ together with 2DLC and
      ESI-MS/MS. RWC at 35% is unique for desiccation tolerant species as it represents
      a distinct phase of the dehydration process where induction of late protection
      mechanisms are initiated. We reproducibly identified 122 proteins with
      confidence>=95% (rho<0.05). In response to dehydration, 65% of the identified
      proteins had the same protein abundance as the hydrated, 22% were shown to be
      more abundant while 9.8% were less abundant. Classification of the nuclear
      proteins according to GO annotation showed that most proteins were part of
      cellular processes (77.43%) and had binding activity (85.47%) respectively.
      Ontological classification according to Interpro and Pfam databases categorized
      most nuclear proteins as part of gene regulation (21%) while the functions of the
      mapped proteins using MapMan showed involvement in protein synthesis (22%),
      degradation (9%), DNA structure (8%) and regulation (8%).

PMID- 22361343
TI  - Management of unknown primary head and neck squamous cell carcinoma.

PMID- 22361342
TI  - Mapping the growth hormone--Stat5b--IGF-I transcriptional circuit.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert powerful
      influences on somatic growth, metabolism, and tissue repair, and have been
      implicated in aging and carcinogenesis. Since the formulation of the somatomedin
      hypothesis over 50 years ago, GH and IGF-I have been linked intimately to one
      another. Recent studies have established that GH potently stimulates IGF-I gene
      transcription, and through this mechanism controls production of IGF-I. A key
      mediator of the GH-IGF-I biosynthetic pathway is the latent transcription factor
      Stat5b. This review summarizes the potentially complex mechanistic relationship
      between GH action, Stat5b, and IGF-I gene activation, and suggests that Stat5b
      may have a broad role in mediating IGF-I gene regulation in response to diverse
      physiological inputs.

PMID- 22361344
TI  - Congenital cholesteatoma: clinical features and growth patterns.
AB  - OBJECTIVE: The clinical features and patterns of growth, relative to age, were
      examined in patients with congenital cholesteatoma to investigate disease
      progression and site of origin. PATIENTS AND METHODS: We retrospectively reviewed
      72 children younger than 15 years with intraoperatively confirmed congenital
      cholesteatoma diagnosed using the inclusion criteria of Levenson et al. Patient
      demographics, history, and otoscopic and operative findings were evaluated.
      Correlation between mass volumetric and operation age was analyzed in patients
      with closed-type masses. Parameters of disease extent of middle ear quadrant,
      ossicular erosion, attic involvement, invasion of the mastoid cavity, and type of
      mass were assessed relative to age at operation. RESULTS: Mean patient age was
      63.1 months (range, 20-179 months), with 51 patients (70.8%) being asymptomatic
      and diagnosed incidentally. Nineteen patients (26.4%) had closed-type cystic
      masses, and 53 (73.6%) had open-type lesions. The volume of closed-type masses
      was linearly correlated with age at operation. Logistic regression showed that
      increased age at operation was associated with a lower proportion of
      anterosuperior quadrant lesions, resulting in uncertainty about the site of
      origin. The possibility of open-type masses also increased according to age at
      operation. CONCLUSION: Congenital cholesteatoma shows growth and extension over
      time. Early detection and intervention are necessary to avoid advanced disease.

PMID- 22361345
TI  - Use of intravenous immunoglobulin to treat chronic bilateral otomastoiditis in
      the setting of rituximab induced hypogammaglobulinemia.
AB  - The temporal bone may be affected by a variety of systemic pathology because the
      disease nature, location, and extent determine the symptoms. Middle ear and
      mastoid infections may be the initial clinical manifestation of autoimmune and
      acquired immunodeficiency disorders. Rituximab, an anti-CD20 chimeric antibody,
      has become increasingly popular as a therapeutic agent for patients with a wide
      range of autoimmune disorders refractory to standard treatments. Normal levels of
      immunoglobulin levels are usually maintained during and after rituximab therapy,
      and clinical trials to date have shown no statistically significant increase of
      serious infections among patients with autoimmune diseases being treated with
      rituximab (Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et
      al, for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to
      anti-tumor necrosis factor therapy: results of a multicenter, randomized, double
      blind, placebo-controlled, phase III trial evaluating primary efficacy and safety
      at 24 weeks. Arthritis Rheum. 2006;54:2793-2806. Edwards JC, Szczepanski L,
      Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B
      cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N
      Engl J Med. 2004;350:2572-2581). However, there have been several reports of
      opportunistic infections associated with rituximab (Kelesidis T, Daikos G, et al.
      Does rituximab increase the incidence of infectious complications? A narrative
      review. Int J Infect Dis 2011;15:e2-e16. Teichmann LL, Woenckhaus M, Vogel C, et
      al. Fatal Pneumocystis pneumonia following rituximab administration for
      rheumatoid arthritis. Rheumatology 2008;47:1256-1257), as well as cases of it
      accelerating the presentation of hypogammaglobulinemia (Diwakar L, Gorrie S, et
      al. Does rituximab aggravate pre-existing hypogammaglobulinaemia? J Clin Pathol
      2010;63:275-277). Humoral immune defects can cause persistent acute and serous
      otitis media, with the development of chronic suppurative otitis media refractory
      to medical and surgical therapy (Sasaki CT, Askenase P, Dwyer J, et al. Chronic
      ear infection in the immunodeficient patient. Arch Otolaryngol 1981;107:82).
      Here, we describe the first presentation, diagnostic workup, and treatment with
      intravenous immunoglobulin of chronic bilateral otomastoiditis in the setting of
      rituximab-induced hypogammaglobulinemia.

PMID- 22361346
TI  - Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to
      monopolar electrocautery at standard power level settings in a pig model.
AB  - BACKGROUND: Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common
      tools for soft tissue dissection. However, morphological data on the related
      tissue alteration are discordant. We developed an automatic device for
      standardized sample excision and compared quality and depth of morphological
      changes caused by UC and ME in a pig model. METHODS: 100 tissue samples (5 * 3
      cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly
      performed manually or by using the self-constructed automatic device at standard
      power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality
      of tissue alteration and depth of coagulation necrosis were examined
      histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects
      were studied by two-way analysis of variance at a significance level of 5%.
      RESULTS: At the investigated power level settings UC and ME induced qualitatively
      similar coagulation necroses. Mean depth of necrosis was 450.4 +/- 457.8 MUm for
      manual UC and 553.5 +/- 326.9 MUm for automatic UC versus 149.0 +/- 74.3 MUm for
      manual ME and 257.6 +/- 119.4 MUm for automatic ME. Coagulation necrosis was
      significantly deeper (p < 0.01) when UC was used compared to ME. The mode of
      excision (manual versus automatic) did not influence the depth of necrosis (p =
      0.85). There was no significant interaction between dissection tool and mode of
      excision (p = 0.93). CONCLUSIONS: Thermal injury caused by UC and ME results in
      qualitatively similar coagulation necrosis. The depth of necrosis is
      significantly greater in UC compared to ME at investigated standard power levels.

PMID- 22361347
TI  - [Stem cell-based treatment of neurologic diseases].
AB  - Therapeutic strategies based on stem cells are being increasingly used to treat a
      wide range of neurological diseases. Although these strategies were initially
      designed to replace dead cells in injured tissue, the potential of stem cells to
      migrate, secrete trophic factors, and immunomodulate allows their therapeutic use
      as a vehicle for gene therapy, as in Parkinson's disease, or as immunomodulators
      and neuroprotectors in diseases such as multiple sclerosis. This review will
      focus on current clinical and experimental evidence on the treatment of
      neurological disorders with strategies based on stem cells.

PMID- 22361348
TI  - "Our best hope is a cure." Hope in the context of advance care planning.
AB  - OBJECTIVE: Advance care planning (ACP) has the potential to enhance end-of-life
      care, yet often fails to live up to that potential. This qualitative interpretive
      study was designed to explore the process and outcomes of ACP using the patient
      centered Advance Care Planning Interview (PC-ACP) developed by the Respecting
      Choices(r) program in Wisconsin. METHOD: Patients diagnosed with advanced lung
      cancer and close family members were recruited. Nine family dyads participated in
      the PC-ACP interview, which was audio-recorded. Follow-up interviews took place 3
      and 6 months after the PC-ACP interview and were also recorded. Thematic analysis
      was conducted on transcribed interviews using constant comparison. RESULTS:
      Analysis showed that hope was a significant theme in the ACP process and this
      article reports on that theme. Hope for a cure was one of many hopes that
      supported quality of life for the participant dyads. Three themes were
      identified: hope is multifaceted, hope for a cure is well considered, and hope is
      resilient and persistent. The seeming paradox of hoping for a cure of an
      incurable cancer did not interfere with the process of ACP. The dyads engaged in
      explicit discussions of end-of-life scenarios and preferences for care. ACP did
      not interfere with hope and hope for a cure did not interfere with ACP.
      SIGNIFICANCE OF RESULTS: Concerns about false hope are called into question. The
      principle of honoring hope is not necessarily in conflict with the principle of
      truthful communication. This is clinically significant, as the findings suggest
      we need not disrupt hope that we think of as "unrealistic" as long as it supports
      the family to live well. Further, ACP can be successful even in the context of
      hoping for a cure.

PMID- 22361349
TI  - Brace technology thematic series: the progressive action short brace (PASB).
AB  - BACKGROUND: The Progressive Action Short Brace (PASB) is a custom-made thoraco
      lumbar-sacral orthosis (TLSO), devised in 1976 by Dr. Lorenzo Aulisa (Institute
      of Orthopedics at the Catholic University of the Sacred Heart, Rome, Italy). The
      PASB was designed to overcome the limits imposed by the trunk anatomy. Indeed,
      the particular geometry of the brace is able to generate internal forces that
      modify the elastic reaction of the spine. The PASB is indicated for the
      conservative treatment of lumbar and thoraco-lumbar scoliosis. The aim of this
      article is to explain the biomechanic principles of the PASB and the rationale
      underlying its design. Recently published studies reporting the results of PASB
      based treatment of adolescent scoliotic patients are also discussed. DESCRIPTION
      AND PRINCIPLES: On the coronal plane, the upper margin of the PASB, at the side
      of the curve concavity, prevents the homolateral bending of the scoliotic curve.
      The opposite upper margin ends just beneath the apical vertebra. The principle
      underlying such configuration is that the deflection of the inferior tract of a
      curved elastic structure, fixed at the bottom end, causes straightening of its
      upper tract. Therefore, whenever the patient bends towards the convexity of the
      scoliotic curve, the spine is deflected. On the sagittal plane, the inferior
      margins of the PASB reach the pelvitrochanteric region, in order to stabilize the
      brace on the pelvis. The transverse section of the brace above the pelvic grip
      consists of asymmetrical ellipses. This allows the spine to rotate towards the
      concave side only, leading to the continuous generation of derotating moments. On
      the sagittal plane, the brace is contoured so as to reduce the lumbar lordosis.
      The PASB, by allowing only those movements counteracting the progression of the
      curve, is able to produce corrective forces that are not dissipated. Therefore,
      the brace is based on the principle that a constrained spine dynamics can achieve
      the correction of a curve by inverting the abnormal load distribution during
      skeletal growth. RESULTS: Since its introduction in 1976, several studies have
      been published supporting the validity of the biomechanical principles to which
      the brace is inspired. In this article, we present the outcome of a case series
      comprising 110 patients with lumbar and thoraco-lumbar curves treated with PASB
      brace. Antero-posterior radiographs were used to estimate the curve magnitude
      (CM) and the torsion of the apical vertebra (TA) at 5 time points: beginning of
      treatment (t1), one year after the beginning of treatment (t2), intermediate time
      between t1 and t4 (t3), end of weaning (t4), 2-year minimum follow-up from t4
      (t5). The average CM value was 29.3 degrees Cobb at t1 and 13.0 degrees Cobb at
      t5. TA was 15.8 degrees  Perdroille at t1 and 5.0 degrees  Perdriolle at t5.
      These results support the efficacy of the PASB in the management of scoliotic
      patients with lumbar and thoraco-lumbar curves. CONCLUSION: The results obtained
      in patients treated with the PASB confirm the validity of our original
      biomechanical approach. The efficacy of the PASB derives not only from its unique
      biomechanical features but also from the simplicity of its design, construction
      and management.

PMID- 22361350
TI  - Propiconazole-enhanced hepatic cell proliferation is associated with
      dysregulation of the cholesterol biosynthesis pathway leading to activation of
      Erk1/2 through Ras farnesylation.
AB  - Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a
      key enzyme in the biosynthesis of ergosterol in fungi and is widely used in
      agriculture to prevent fungal growth. Metabolomic studies in mice revealed that
      propiconazole increased levels of hepatic cholesterol metabolites and bile acids,
      and transcriptomic studies revealed that genes within the cholesterol
      biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up
      regulated. Hepatic cell proliferation was also increased by propiconazole. AML12
      immortalized hepatocytes were used to study propiconazole's effects on cell
      proliferation focusing on the dysregulation of cholesterol biosynthesis and
      resulting effects on Ras farnesylation and Erk1/2 activation as a primary
      pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway,
      increases cell proliferation in several cancer cell lines and tumors in vivo and
      serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are
      crucial in the farnesylation of the Ras protein by farnesyl transferase.
      Farnesylation targets Ras to the cell membrane where it is involved in signal
      transduction, including the mitogen-activated protein kinase (MAPK) pathway. In
      our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased
      cell proliferation in AML12 cells which was reduced by farnesyl transferase
      inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase
      inhibitor, indicating that this cell system responded to alterations in the
      cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased
      by propiconazole which was reversed by co-incubation with L-744,832 or
      simvastatin. Increasing concentrations of exogenous cholesterol muted the
      proliferative effects of propiconazole and the inhibitory effects of L-733,832,
      results ascribed to reduced stimulation of the endogenous cholesterol
      biosynthesis pathway. Western blot analysis of subcellular fractions from
      control, MVAL or propiconazole-treated cells revealed increased Ras protein in
      the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL
      reversed these effects. Western blot analysis indicated that phosphorylation of
      Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data
      indicate that propiconazole increases cell proliferation by increasing the levels
      of cholesterol biosynthesis intermediates presumably through a negative feedback
      mechanism within the pathway, a result of CYP51 inhibition. This feedback
      mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation.
      These results provide an explanation for the observed effects of propiconazole on
      hepatic cholesterol pathways and on the increased hepatic cell proliferation
      induced by propiconazole in mice.

PMID- 22361351
TI  - Calculated angular responses of an RPL dosemeter to photon and beta radiation.
AB  - The calculated dose equivalent response as a function of the angle has been
      examined for the radiophotoluminescent (RPL) glass dosemeter that was exposed to
      narrow series X-ray, N-60, N-80, N-100, N-150, N-200, N-250, N-300, photon
      sources ((60)Co and (137)Cs) and beta-ray emitter ((90)Sr/(90)Y) while mounted on
      an ISO water slab phantom. The angular dose equivalent responses H(p)(10) and
      H(p)(0.07) were calculated using the Monte Carlo MCNPX code. The RPL dosemeter
      and the phantom were rotated in the horizontal and vertical planes from a variety
      of angles of interest. The results were compared with the experimental data. Good
      agreement was found between the measured and calculated values of the relative
      dose equivalent angular responses of the RPL dosemeter.

PMID- 22361352
TI  - Estimates of the occupational exposure to tenorm in the phosphoric acid
      production plant in Iran.
AB  - Phosphate rock is used world wide for manufacturing phosphoric acid and several
      chemical fertilisers. It is known that the phosphate rock contains various
      concentrations of uranium, thorium, radium and their daughters. The subject of
      this study is the evaluation of the radiation exposure to workers in the
      phosphoric acid production plant due to technologically enhanced naturally
      occurring radioactive materials that can result from the presence of naturally
      occurring radioactive materials in phosphate ores used in the manufacturing of
      phosphoric acid. Radiation exposure due to direct gamma radiation, dust
      inhalation and radon gas has been investigated and external and internal doses of
      exposed workers have been calculated. Natural radioactivity due to (40)K, (226)Ra
      and (232)Th have been measured in phosphate rock, phosphogypsum, chemical
      fertilisers and other samples by gamma spectrometry system with a high-purity
      germanium. The average concentrations of (226)Ra and (40)K observed in the
      phosphate rock are 760 and 80 Bq kg(-1), respectively. Annual effective dose from
      external radiation had a mean value of ~0.673 mSv y(-1). Dust sampling revealed
      greatest values in the storage area. The annual average effective dose from
      inhalation of long-lived airborne was 0.113 mSv y(-1). Radon gas concentrations
      in the processing plant and storage area were found to be of the same value as
      the background. In this study the estimated annual effective doses to workers
      were below 1 mSv y(-1).

PMID- 22361353
TI  - CD8 T cell quiescence revisited.
AB  - Naive T cells are typically considered to be in a default state of quiescence,
      whereas memory T cells undergo basal proliferation and quickly exhibit effector
      responses when stimulated. Over the past few years, however, a more complex
      picture has emerged, with evidence that naive T cell quiescence is actively
      enforced, and that heterogeneity among naive T cells influences their capacity to
      escape quiescence in response to homeostatic cues. Furthermore, the active state
      of memory T cells may also be instructed, requiring contact with dendritic cells
      to avoid reversion to quiescence. Here, we discuss these new findings and propose
      that there is much more flexibility in the quiescent state of naive and memory T
      cells than previously thought.

PMID- 22361355
TI  - Catatonia and mania in patient with AIDS: treatment with lorazepam and
      risperidone.
AB  - A 30-year-old woman presented with psychiatric symptoms and was found to be HIV
      positive prior to admission to the hospital. We present the first case report of
      catatonia and mania in an HIV-positive subject unrelated to infectious processes.
      The catatonic symptoms were alleviated by intravenous lorazepam, and manic
      symptoms were adequately treated with risperidone. Clinicians need to be aware
      that HIV infection should be considered in all patients with new-onset mania
      alternating with catatonia or in those with HIV risk factors.

PMID- 22361354
TI  - ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA
      damage.
AB  - The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome
      stability and cancer prevention by controlling the key proteins involved in the
      DNA damage response. Despite this important role in controlling other proteins,
      USP7 itself has not been recognized as a target for regulation. Here, we report
      that USP7 regulation plays a central role in DNA damage signal transmission. We
      find that stabilization of Mdm2, and correspondingly p53 downregulation in
      unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is
      phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes
      USP7S and thus contributes to Mdm2 stabilization and downregulation of p53. After
      ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein
      phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation
      and accumulation of p53. Our findings provide a quantitative transmission
      mechanism of the DNA damage signal to coordinate a p53-dependent DNA damage
      response.

PMID- 22361356
TI  - Fabrication of pseudo-ceramide-based lipid microparticles for recovery of skin
      barrier function.
AB  - The recovery of skin barrier functions was investigated with pseudo-ceramide
      based lipid microparticles. The microparticles were prepared by using a fluid bed
      technique where lipid components (a pseudo-ceramide, cholesterol and a fatty
      acid) were coated on a sugar seed, and a polymer was subsequently coated on the
      lipid microparticles. The microparticles contained large amount of pseudo
      ceramide, and the pseudo-ceramide was in the form of lamellar structures mixed
      with other lipid components. In addition, the microparticles were stably
      dispersed in aqueous media or emulsion systems without any disruption of the
      microparticles' structures, thereby supplying sufficient amount of the pseudo
      ceramide to skins for improving skin barrier functions such as preventing water
      loss. Such a role of the microparticles was proven by evaluating in vivo the
      efficacy of the lipid microparticles in reducing a trans-epidermal water loss
      (TEWL) of impaired murine skins. As a result, the novel pseudo-ceramide-based
      lipid microparticles for barrier recovery may potentially be applied in the field
      of dermatology, cosmetics and pharmaceuticals.

PMID- 22361357
TI  - Intrinsic bacterial burden associated with intensive care unit hospital beds:
      effects of disinfection on population recovery and mitigation of potential
      infection risk.
AB  - BACKGROUND: Commonly touched items are likely reservoirs from which patients,
      health care workers, and visitors may encounter and transfer microbes. A
      quantitative assessment was conducted of the risk represented by the intrinsic
      bacterial burden associated with bed rails in a medical intensive care unit
      (MICU), and how disinfection might mitigate this risk. METHODS: Bacteria present
      on the rails from 36 patient beds in the MICU were sampled immediately before
      cleaning and at 0.5, 2.5, 4.5, and 6.5 hours after cleaning. Beds were sanitized
      with either a bottled disinfectant (BD; CaviCide) or an automated bulk-diluted
      disinfectant (ABDD; Virex II 256). RESULTS: The majority of bacteria recovered
      from the bed rails in the MICU were staphylococci, but not methicillin-resistant
      Staphylococcus aureus. Vancomycin-resistant enterococci were recovered from 3
      beds. Bottled disinfectant reduced the average bacterial burden on the rails by
      99%. However, the burden rebounded to 30% of that found before disinfection by
      6.5 hours after disinfection. ABDD reduced the burden by an average of 45%, but
      levels rebounded within 2.5 hours. The effectiveness of both disinfectants was
      reflected in median reductions to burden of 98% for BD and 95% for ABDD.
      CONCLUSIONS: Cleaning with hospital-approved disinfectants reduced the intrinsic
      bacterial burden on bed rail surfaces by up to 99%, although the population,
      principally staphylococci, rebounded quickly to predisinfection levels.

PMID- 22361359
TI  - Medical students' knowledge, perceptions, and behavioral intentions towards the
      H1N1 influenza, swine flu, in Pakistan: a brief report.
AB  - This study was conducted to assess the knowledge of H1N1 among medical students,
      their perceptions, and behavioral intentions in the wake of the H1N1 pandemic
      influenza. There were significant gaps in important self-isolation protocols and
      preventive measures. Increased contact with both patients and colleagues can lead
      to unintentional transmission and contraction of influenza. Universities should
      introduce and encourage infection control guidelines into routine curriculum.

PMID- 22361358
TI  - Risk factors associated with linezolid-nonsusceptible enterococcal infections.
AB  - Linezolid is one of few treatment options available for vancomycin-resistant
      enterococci. The present study investigated risk factors for linezolid
      nonsusceptible enterococci using a case-control study of 15 cases and 60 control
      patients. Previous hospitalization, admission to a medical service, comorbidity,
      and linezolid and sulfonamide therapy were identified as risk factors.

PMID- 22361360
TI  - Disparity in infection control practices for multidrug-resistant
      Enterobacteriaceae.
AB  - BACKGROUND: There is a lack of empiric evidence regarding the optimal approach to
      controlling the transmission of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE). In
      this context, we expect that infection control practices for these organisms vary
      widely between hospitals. METHODS: A survey examining infection control practices
      for ESBL-E and CRE was distributed to 6 academic and 9 community hospitals in
      Toronto, Canada. RESULTS: All hospitals responded to the survey. Among 15
      hospitals in 1 geographic area, 8 different approaches to the management of ESBL
      E were utilized. There was wide variation in the use infection control practices
      including admission screening (53% and 53%), contact precautions (53% and 100%),
      and isolation (60% and 100%) for ESBL-E and CRE, respectively. Of hospitals
      performing admission screening, 75% used risk factor-based screening for ESBL-E
      and CRE. CONCLUSION: Even within a single geographic area, there is wide
      variation in infection control strategies to contain or control ESBL-E and CRE.
      These results are concerning given evidence that a coordinated approach may be
      required to prevent or limit the emergence of CRE.

PMID- 22361361
TI  - Outpatient costs in pharmaceutically treated diabetes patients with and without a
      diagnosis of depression in a Dutch primary care setting.
AB  - BACKGROUND: To assess differences in outpatient costs among pharmaceutically
      treated diabetes patients with and without a diagnosis of depression in a Dutch
      primary care setting. METHODS: A retrospective case control study over 3 years
      (2002-2004). Data on 7128 depressed patients and 23772 non-depressed matched
      controls were available from the electronic medical record system of 20 general
      practices organized in one large primary care organization in the Netherlands. A
      total of 393 depressed patients with diabetes and 494 non-depressed patients with
      diabetes were identified in these records. The data that were extracted from the
      medical record system concerned only outpatient costs, which included GP care,
      referrals, and medication. RESULTS: Mean total outpatient costs per year in
      depressed diabetes patients were ?1039 (SD 743) in the period 2002-2004, which
      was more than two times as high as in non-depressed diabetes patients (?492, SD
      434). After correction for age, sex, type of insurance, diabetes treatment, and
      comorbidity, the difference in total annual costs between depressed and non
      depressed diabetes patients changed from ?408 (uncorrected) to ?463 (corrected)
      in multilevel analyses. Correction for comorbidity had the largest impact on the
      difference in costs between both groups. CONCLUSIONS: Outpatient costs in
      depressed patients with diabetes are substantially higher than in non-depressed
      patients with diabetes even after adjusting for confounders. Future research
      should investigate whether effective treatment of depression among diabetes
      patients can reduce health care costs in the long term.

PMID- 22361362
TI  - Factors in narratives to questions in the Short-Term Life Review interviews of
      terminally ill cancer patients and utility of the questions.
AB  - OBJECTIVE: Although the Short-Term Life Review elevated the spiritual well-being
      of terminally ill cancer patients in our previous study, we have not examined
      what patients reviewed for each question item of it. We examined factors in
      narratives to questions in the Short-Term Life Review interviews of terminally
      ill cancer patients and utility of the questions. METHOD: Thirty-four terminally
      ill cancer patients received the Short-Term Life Review interview in which there
      were two sessions. In the first session patients reviewed their lives, and an
      interviewer made a simple album of the patient based on patients' narrative.
      After 1 week, there was a second session. Qualitative analysis was conducted on
      patients' answers to each question using computational word mining, and factors
      were identified. RESULTS: Twenty patients' narratives were analyzed. "Human
      relationships" was identified under "important things in life." "Pleasant
      memories" were associated with "impressive memories." "Illness" and "marriage and
      divorce" were related to "turning points in the life." "Raising children and
      education" and "company or work" were identified as "roles in life."
      "Achievements at work" were identified with "pride." "Message to my children" was
      identified with "what I want to say to my family." "To live sincerely" and
      "consideration for others" were identified as "advice for the next generation."
      Patients reviewed few for topics such as "pride," "what I want to say to my
      family," "advice for the next generation," and "summing up my life." SIGNIFICANCE
      OF RESULTS: Factors such as human relationships, raising children, and education
      as a role and source of pride, and concerns about children's future, were
      associated with elevating spiritual well-being. Question to which that patients
      easily answered were selected.

PMID- 22361363
TI  - Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye
      movement sleep deprivation (REMSD) on developmentally regulated, long-term
      potentiation (LTP) in visual cortex slices.
AB  - Work in this laboratory demonstrated a role for rapid eye movement sleep (REMS)
      in critical period (CP), postnatal days (P) 17-30, synaptic plasticity in visual
      cortex. Studies in adolescent rats showed that REMS deprivation (REMSD)
      reinitiates a developmentally regulated form of synaptic plasticity that
      otherwise is observed only in CP animals. Subsequent work added that REMSD
      affects inhibitory mechanisms that are thought to be involved in terminating the
      CP. Neurotrophins are implicated in the synaptic plasticity that underlies CP
      maturation and also final closure of the CP in visual cortex. Expression of brain
      derived neurotrophic factor (BDNF) is dependent upon neuronal activity, and REMSD
      may block BDNF expression. We propose that REMS contributes to the maturation of
      visual cortex through regulation of BDNF expression and consequent, downstream
      increase in cortical inhibitory tone. In this study, osmotic minipumps delivered
      BDNF into visual cortex on one side of brain. The opposite hemisphere was not
      implanted and served as an internal control. We tested the hypothesis that BDNF
      is blocked by REMSD in late-adolescent rats and investigated whether replacing
      BDNF prevents induction of LTPWM-III by theta burst stimulation (TBS). We also
      assessed relative inhibitory tone in visual cortex with paired-pulse stimulation
      (PPS) in animals that were similarly REMSD- and BDNF-infused. After REMSD, both
      hemispheres were prepared in parallel for in vitro synaptic plasticity studies
      (LTPWM-III or PPS). In visual cortex of REMSD rats on the side receiving BDNF
      infusions (8 of 8 animals), TBS consistently failed to induce LTPWM-III. In
      contrast, LTPWM-III was obtained (5 of 5 animals) in the matched, non-infused
      hemisphere, as expected in rats of this age. REMSD animals that were unilaterally
      infused with saline produced LTPWM-III in both hemispheres. PPS studies in
      another group of REMSD animals that were unilaterally BDNF-infused displayed age
      appropriate inhibition of the second response on the BDNF-infused side (5/5),
      whereas on the non-infused side facilitation was observed (3/3). Intracortical
      infusion of BDNF in REMSD adolescent rats appears to restore neurochemical
      processes necessary for termination of the CP for developmentally regulated
      synaptic plasticity in visual cortex. The results suggest that REMSD blocks BDNF
      expression and also maturation of inhibitory processes in adolescent visual
      cortex. These data support REMS' function in brain development.

PMID- 22361364
TI  - Effects of thienorphine on release of dopamine and noradrenalin: an in vivo
      microdialysis study in rats.
AB  - Thenorphine is a new potent long-acting partial opioid agonist. In present study,
      the effect of thienorphine on noradrenalin (NA) in the locus coeruleus (LC) and
      dopamine (DA) and its metabolites in the nucleus acumbens (NAc) and the striatum
      were examined in freely moving rats during acute and chronic thienorphine
      treatment followed by naloxone-precipitated withdrawal using the in vivo
      microdialysis technique. Acute thienorphine (1.0mg/kg, s.c.) treatment had no
      effect on the level of NA in the LC and the level of DA in the NAc and the
      striatum. Chronic thienorphine (1.0mg/kg, s.c.) third per day for continued 5
      days treatment followed by naloxone-precipitated (5.0mg/kg, i.p.) had not alter
      the extracellular NA level in the LC and the extracellular level of DA in the NAc
      and the striatum, but significantly increased the level of DOPAC in the striatum.
      These changes are thought to reflect a direct effect of thienorphine on release
      of NA and DA. Thus thienorphine deserves further study as a new treatment for
      opioid dependence.

PMID- 22361365
TI  - Hidden conflicts: explanations make inconsistencies harder to detect.
AB  - A rational response to an inconsistent set of propositions is to revise it in a
      minimal way to restore consistency. A more important psychological goal is
      usually to create an explanation that resolves the inconsistency. We report five
      studies showing that once individuals have done so, they find inconsistencies
      harder to detect. Experiment 1 established the effect when participants explained
      inconsistencies, and Experiment 2 eliminated the possibility that the effect was
      a result of demand characteristics. Experiments 3a and 3b replicated the result,
      and showed that it did not occur in control groups that evaluated (or justified)
      which events in the pairs of assertions were more surprising. Experiment 4
      replicated the previous findings, but the participants carried out all the
      conditions acting as their own controls. In all five studies, control conditions
      established that participants were able to detect comparable inconsistencies.
      Their explanations led them to re-interpret the generalizations as holding by
      default, and so they were less likely to treat the pairs of assertions as
      inconsistent. Explanations can accordingly undo the devastating consequences of
      logical inconsistencies, but at the cost of a subsequent failure to detect them.

PMID- 22361367
TI  - Arousal gating motor events in NFLE--a window on the boundary between physiology
      and pathology.

PMID- 22361366
TI  - Association of body weight and physical activity with blood pressure in a rural
      population in the Dikgale village of Limpopo Province in South Africa.
AB  - BACKGROUND: Africa is faced with an increasing burden of hypertension attributed
      mainly to physical inactivity and obesity. Paucity of population based evidence
      in the African continent hinders the implementation effective preventive and
      control strategies. The aim of this study was to determine the association of
      body weight and physical activity with blood pressure in a rural black population
      in the Limpopo Province of South Africa. METHODS: A convenient sample of 532
      subjects (396 women and 136 men) between the ages 20-95 years participated in the
      study. Standard anthropometric measurements, blood pressure, and physical
      activity were recorded by trained field workers. RESULTS: Anthropometric
      measurements showed that a high percentage of women were significantly (p <
      0.001) overweight and obese than men. Hypertension was significantly high among
      women (38.1%) compared to men (27.9%). In the univariate analysis mean body mass
      index (BMI), waist circumference (WC), hip circumference (HC) and waist hip ratio
      (WHR) showed a significant positive association (p <= 0.05) with systolic and
      diastolic BP in women, and only WHR was statistically significant in men. The
      odds of being hypertensive also increased with BMI, WC and WHR in both women and
      men, including HC in women. No relationship was found between physical activity
      and high blood pressure. In the multivariate analysis only increase in HC and WHR
      was consistently associated with increase in SBP in women and WHR with
      hypertension in men. CONCLUSIONS: The study findings indicate that women in this
      black South African rural population are overweight and obese than men and are at
      higher risk of hypertension as determined by selected anthropometric parameters.

PMID- 22361368
TI  - Nerve conduction studies: basic concepts and patterns of abnormalities.
AB  - As a fundamental component of the electrodiagnostic evaluation, nerve conduction
      studies provide valuable quantitative and qualitative insights into neuromuscular
      function. Nerve conduction studies are useful in the identification and
      characterization of several neuromuscular disorders, particularly disorders of
      peripheral nerve. Abnormalities of nerve conduction studies may anticipate
      specific pathologic processes, such as demyelination or axonal loss, and may
      provide precise localization of focal nerve lesions. As with other elements of
      the electrodiagnostic evaluation, nerve conduction studies must be performed with
      careful attention to technique and must be interpreted in a clinical context.

PMID- 22361369
TI  - Needle electromyography: basic concepts and patterns of abnormalities.
AB  - Needle electromyography (EMG) records electrical signals generated from muscle
      fibers and interprets the signals to characterize underlying pathologic changes
      that are occurring in motor units within muscles. Different types of
      spontaneously firing waveforms and motor unit potential changes occur with
      different neuromuscular disorders. The performance of reliable EMG studies
      depends on the technical skills of the physician in inserting, moving, recording
      with a needle electrode, and analyzing electric signals recorded from muscle.
      This article reviews the technique of needle EMG and recognition and
      interpretation of various EMG waveforms. The author presents several
      demonstrative videos at www.neurologic.theclinics.com.

PMID- 22361370
TI  - The electrodiagnostic approach to carpal tunnel syndrome.
AB  - CTS is a clinically defined syndrome; however, there is value added by an
      evidence-based electrodiagnostic approach to (1) efficiently confirm the
      diagnosis (particularly before invasive interventions), (2) to identify
      neurogenic mimickers or superimposed processes that may influence the response to
      treatment, and (3) to stratify the degree of neurogenic injury to help the
      clinician make management decisions in conjunction with the severity of the
      clinical symptoms. The literature on the electrodiagnostic diagnosis of CTS is
      reviewed and an evidence based diagnostic algorithm is proposed. Confounders to
      CTS electrodiagnostic diagnosis are discussed (crossovers, peripheral neuropathy,
      and recurrent symptoms after surgical release).

PMID- 22361371
TI  - Electrodiagnostic evaluation of ulnar neuropathy and other upper extremity
      mononeuropathies.
AB  - Upper extremity mononeuropathies are some of the common disorders seen in
      neurophysiology laboratories. Electrophysiologic studies rely on accurate
      localization based on knowledge of applicable anatomy and features of history and
      physical examination. Careful electrodiagnostic studies provide an accurate
      diagnosis, help localize the lesion site, exclude alternate diagnoses, reveal
      unsuspected diagnoses, determine pathophysiology of lesions, and assess severity,
      timeframe, and prognosis of lesions. This article discusses the electrodiagnostic
      approach to ulnar neuropathy, proximal median neuropathy, radial neuropathy,
      musculocutaneous neuropathy, axillary neuropathy, suprascapular neuropathy, and
      long thoracic neuropathy. Pertinent aspects of the history and physical
      examination, nerve conduction studies, and electromyography are presented.

PMID- 22361372
TI  - Electrodiagnostic evaluation of lower extremity mononeuropathies.
AB  - This article discusses the anatomy of lower limb mononeuropathies and reviews the
      general approach to evaluating patients in the electrodiagnostic laboratory with
      suspected mononeuropathies of the lower limb. Through illustrative cases of
      patients presenting with a floppy foot, buckling knee, or painful foot, the
      approaches using nerve conduction studies and needle electromyography are
      reviewed, and the pattern of findings of peroneal, tibial, sciatic, femoral, and
      obturator neuropathies is shown.

PMID- 22361373
TI  - Electrodiagnosis of peripheral neuropathy.
AB  - Electrodiagnostic studies are an important component of the evaluation of
      patients with suspected peripheral nerve disorders. The pattern of findings and
      the features that are seen on the motor and sensory nerve conduction studies and
      needle electromyography can help to identify the type of neuropathy, define the
      underlying pathophysiology (axonal or demyelinating), and ultimately help to
      narrow the list of possible causes. This article reviews the electrodiagnostic
      approach to and interpretation of findings in patients with peripheral
      neuropathies.

PMID- 22361374
TI  - Electrodiagnostic assessment of the brachial plexus.
AB  - The brachial plexus is one of the largest and most complex structures of the
      peripheral nervous system and, as such, cannot be studied by a single nerve
      conduction study (NCS) or muscle sampled by needle electrode examination (NEE).
      Typically, the screening sensory NCS is used and expanded to identify the region
      of involvement, the motor NCS is applied to determine the severity of the
      process, and the NEE is used to further characterize the lesion. Our approach to
      the electrodiagnostic assessment of the brachial plexus is the focus of this
      article; 3 electrodiagnostic cases with discussion follow this article.

PMID- 22361375
TI  - Approach to the patient with suspected radiculopathy.
AB  - Radiculopathy is a common neurologic disorder. Electrodiagnosis can provide a
      physiologic assessment of the localization, degree of axon loss, severity, and
      chronicity of the intraspinal canal lesion, and distinguish it from other
      neuromuscular disorders. This article reviews electrodiagnostic aspects related
      to evaluating patients with suspected radiculopathies.

PMID- 22361376
TI  - The electrophysiology of the motor neuron diseases.
AB  - The motor neuron diseases are a set of disorders associated with the selective
      degeneration of motor neurons. Amyotrophic lateral sclerosis (ALS) is the most
      common and confers the gravest prognosis. Although ALS occurs with known genetic
      causes in a small minority, other motor neuron disorders have well-defined
      genetic mutations. Electrodiagnostic testing is important to distinguish these
      various disorders. Electrodiagnostic testing is also crucial for distinguishing
      potential mimic syndromes, such as multifocal motor neuropathy and inclusion body
      myositis. Newer neurophysiology techniques have been developed in the past
      several years. What role these techniques will play in clinical practice is
      currently unknown.

PMID- 22361377
TI  - Evaluation of neuromuscular junction disorders in the electromyography
      laboratory.
AB  - Neuromuscular junction (NMJ) disorders may be demonstrated using repetitive nerve
      stimulation (RNS) testing and single-fiber electromyography (SFEMG). RNS testing
      with low frequency stimulation reduces the safety factor of neuromuscular
      transmission (NMT) and may elicit decrementing compound muscle action potential
      (CMAP) responses. Exercise or tetanic nerve stimulation may potentiate
      acetylcholine release in presynaptic NMT disorders with CMAP facilitation. SFEMG
      is a selective recording technique assessing MFAPs within the same motor unit.
      Jitter is increased in NMJ disorders, and is the temporal variability between
      these MFAPs. Impulse blocking reflects failure of NMT. RNS and SFEMG findings in
      NMJ disorders are reviewed.

PMID- 22361378
TI  - Electrodiagnostic approach to the patient with suspected myopathy.
AB  - Electrodiagnostic testing is a useful component of the approach to a patient with
      suspected myopathy. It follows the history and is guided by the neurologic
      examination findings. Uncovering various electrodiagnostic patterns (eg,
      fibrillation potentials with short-duration motor unit potentials, short-duration
      motor unit potentials without fibrillation potentials, myotonic discharges, and
      short-duration motor unit potentials with complex repetitive discharges) can lead
      to more targeted laboratory testing and a refined differential diagnosis.
      Electromyography may also be used to detect subclinical myopathy, assess disease
      activity, and help select a suitable muscle for biopsy.

PMID- 22361379
TI  - Electrodiagnostic approach to cranial neuropathies.
AB  - This article is a general review of cranial nerve conduction studies, including
      techniques as well as interpretation of data. The needle examination of various
      cranial innervated muscles is also reviewed. The nerve conduction studies include
      the blink, masseter (jaw jerk), and masseter inhibitory reflexes, which evaluate
      the trigeminal (blink and jaw jerk) and facial nerves (blink), as well as
      trigeminal, facial, and spinal accessory motor stimulation. The needle
      examination techniques for certain voluntary muscles innervated by cranial nerves
      V, VII, X, XI, and XII are also described.

PMID- 22361380
TI  - Technical issues and potential complications of nerve conduction studies and
      needle electromyography.
AB  - Nerve conduction studies and needle electromyography provide important and
      complementary information as part of an electrodiagnostic study. Potential
      technical problems that are encountered during the studies may interfere with
      accurate and reliable acquisition of information and interpretation of the data.
      Recognition, identification, and correction of various technical problems are
      critical to the reliable interpretation of any electrodiagnostic study. Both
      techniques are safe, but there are potential risks and complications in rare
      instances. This article reviews technical considerations to assist in accurate
      interpretation and safe performance of an electrodiagnostic study.

PMID- 22361381
TI  - Coding and reimbursement of electrodiagnostic studies.
AB  - Current Procedural Terminology (CPT) codes for electrodiagnostic procedures
      include codes for nerve conduction studies, nerve tests with preconfigured
      arrays, reflex tests, electromyography (EMG), and chemodenervation procedures.
      The codes are updated yearly. For 2012, there are new EMG codes to be used when
      the patient also receives nerve conduction studies on the same date. Coding for
      bilateral chemodenervation procedures has also been clarified. The CPT codes for
      neurologic procedures are not defined to include consultation or other evaluation
      and management services. When appropriate, codes for these services and skills
      may be submitted along with the codes for any neurologic procedures.

PMID- 22361382
TI  - A day in the EMG laboratory: case studies of 10 patients with different clinical
      problems.
AB  - This article reviews 10 cases that have been evaluated in the electromyography
      laboratory, which represent a variety of clinical problems that may be referred
      for electrodiagnostic evaluation. The clinical and electrodiagnostic findings are
      presented, and practical points related to the approach taken in the evaluation
      are discussed.

PMID- 22361384
TI  - Australian carybdeid jellyfish causing "Irukandji syndrome".
AB  - The Australian carybdeid jellyfish associated with Irukandji syndrome is Carukia
      barnesi, (Barnes' jellyfish). Other Australian carybdeid jellyfish that may be
      associated with the syndrome include Carukia shinju, Carybdea xaymacana, Malo
      maxima, Malo kingi, Alatina mordens, Gerongia rifkinae, and Morbakka fenneri
      ("Morbakka"). These small jellyfish are difficult to capture and identify. They
      are located offshore of the coasts of Australian states including Queensland, The
      Northern Territory, Western Australia and South Australia. The syndromic illness,
      resulting from a characteristic relatively minor sting, develops after about 30
      minutes and consists of severe muscle pains especially of the lower back, muscle
      cramps, vomiting, sweating, agitation, vasoconstriction, prostration,
      hypertension and in cases of severe envenomation, acute heart failure. The
      mechanisms of actions of their toxins are obscure but they appear to include
      modulation of neuronal sodium channels leading to massive release of endogenous
      catecholamines (C. barnesi, A. mordens and M. maxima) and thereby to possible
      stress-induced cardiomyopathy. In addition, pore formation may occur in
      myocardial cellular membranes (C. xaymacana). In human cases of severe
      envenomation, systemic hypertension and myocardial dysfunction are associated
      with membrane leakage of troponin. Clinical management includes parenteral
      analgesia, antihypertensive therapy, oxygen and mechanical ventilation. No
      effective first-aid is known. Large knowledge gaps exist in biology of the
      jellyfish, their distribution, their toxins and mode of actions and in treatment
      of the Irukandji syndrome.

PMID- 22361386
TI  - Is cortisol a modulator of interferon tau action in the endometrium during early
      pregnancy in cattle?
AB  - Glucocorticoids (GCs) were recently found to be potent modulators of the
      secretion of uterine prostaglandins (PGs) in ruminants. The aim of the present
      study was to examine whether GCs may serve as a mediator/modulator of interferon
      tau (IFNT) action during early pregnancy in cows. We examined whether IFNT
      affects cortisol output and expression of GC receptors (NR3C1) and 11beta
      hydroxysteroid dehydrogenases (enzymes responsible for GC conversion: HSD11B1 and
      HSD11B2) in bovine endometrium. Endometrial tissues were collected from cyclic
      and pregnant cows on Days 16-17. Endometrial stromal and epithelial cells were
      isolated from uteri from cyclic cows in the early luteal phase (Days 2-5). The
      mRNA and protein expressions of NR3C1, HSD11Bs in endometrial strips and cultured
      cells were analyzed. Endometrial slices and isolated cells were incubated with
      cortisone in the presence or absence of IFNT and HSD11B1 activity was evaluated.
      IFNT increased HSD11B1 activity in endometrial strips and both types of
      endometrial cells. IFNT influenced NR3C1 and HSD11Bs mRNA and protein expression
      in epithelial and stromal cells. Expressions of HSD11Bs and NR3C1 mRNA and
      protein in bovine endometrium were different on Days 16-17 of the estrous cycle
      compared with early pregnancy. Cortisol changed basal and IFNT-stimulated PGE2
      secretion in the bovine endometrium. The overall results suggest that cortisol
      acts as modulator and/or mediator of IFNT actions in bovine uterus and that IFNT
      regulates PG secretion by up-regulating local cortisol, resulting in the
      maintenance of the corpus luteum during early pregnancy in cattle.

PMID- 22361385
TI  - Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper
      overload.
AB  - Mycobacterium tuberculosis is an important bacterial pathogen with an extremely
      slow growth rate, an unusual outer membrane of very low permeability and a
      cunning ability to survive inside the human host despite a potent immune
      response. A key trait of M. tuberculosis is to acquire essential nutrients while
      still preserving its natural resistance to toxic compounds. In this regard,
      copper homeostasis mechanisms are particularly interesting, because copper is an
      important element for bacterial growth, but copper overload is toxic. In M.
      tuberculosis at least two enzymes require copper as a cofactor: the Cu/Zn
      superoxide dismutase SodC and the cytochrome c oxidase which is essential for
      growth in vitro. Mutants of M. tuberculosis lacking the copper metallothionein
      MymT, the efflux pump CtpV and the membrane protein MctB are more susceptible to
      copper indicating that these proteins are part of a multipronged system to
      balance intracellular copper levels. Recent evidence showed that part of copper
      toxicity is a reversible damage of Fe-S clusters of dehydratases and the
      displacement of other divalent cations such as zinc and manganese as cofactors in
      proteins. There is accumulating evidence that macrophages use copper to poison
      bacteria trapped inside phagosomes. Here, we review the rapidly increasing
      knowledge about copper homeostasis in M. tuberculosis and contrast those with
      similar mechanisms in Escherichia coli. These findings reveal an intricate
      interplay between the host which aims to overload the phagosome with copper and
      M. tuberculosis which utilizes several mechanisms to reduce the toxic effects of
      excess copper.

PMID- 22361387
TI  - Angiotensin II type 2 receptor-interacting protein prevents vascular senescence.
AB  - Angiotensin II type 2 (AT(2)) receptor-interacting protein (ATIP), which
      interacts with the C-terminal tail of the AT(2) receptor, regulates the functions
      of the AT(2) receptor. We have reported that AT(2) receptor stimulation
      attenuated vascular senescence. Therefore, we examined the possible negative role
      of ATIP in regulating vascular senescence. We generated ATIP-transgenic (Tg)
      mice, and cultured vascular smooth muscle cells (VSMCs). Persistent angiotensin
      II stimulation induced increases in SA-beta-gal-positive cells and the level of a
      DNA damage marker, 8-OHdG in VSMC, whereas these effects of angiotensin II were
      attenuated in VSMC prepared from ATIP-Tg mice. Angiotensin II treatment also
      upregulated the expression of methyl methanesulfonate-sensitive 2 (MMS2), a DNA
      repair factor, and Src homology 2 domain-containing protein-tyrosine phosphatase
      1 (SHP-1) activity, whereas these effects of angiotensin II were further enhanced
      in ATIP-Tg VSMC. In vivo, x-ray irradiation to mice caused increases in SA-beta
      gal-positive area and 8-OHdG level in the thoracic aorta; however, these effects
      were reduced in ATIP-Tg mice, with a significant increase in MMS2 expression.
      These results suggest that ATIP could inhibit VSMC senescence, involving MMS2
      expression and SHP-1 activity. ATIP might be a new therapeutic molecule to treat
      vascular aging and age-related vascular diseases.

PMID- 22361389
TI  - The murderer is the bed: an unusual case of death by traumatic asphyxia in a
      hotel folding bunk bed.
AB  - This paper presents the first referenced case on a death by traumatic asphyxia in
      a folding bunk bed. A middle-aged man was found dead in a hotel room trapped into
      a lower folding bunk bed where he had been sleeping after a party. The autopsy
      showed signs of asphyxia and excluded signs of struggle and sexual intercourse.
      Toxicological analyses revealed alcohol intoxication. A differential diagnosis of
      the manner of death including a technical study of the bed which contributed to
      understand the circumstances of death was made. The medico-legal investigation of
      the case strongly supported the hypothesis of an accidental death by traumatic
      asphyxia.

PMID- 22361388
TI  - Anti-malarial activity of geldanamycin derivatives in mice infected with
      Plasmodium yoelii.
AB  - BACKGROUND: Geldanamycin (GA), a benzoquinone ansamycin antibiotic has been shown
      in vitro to possess anti-plasmodial activity. Pharmacological activity of this
      drug is attributed to its ability to inhibit PfHSP90. The parasite growth arrest
      has been shown to be due to drug-induced blockage of the transition from ring to
      trophozoite stage. To further evaluate the consequences of this pharmacodynamic
      feature, the anti-malarial activity of GA analogs with enhanced drug properties
      in a Plasmodium-infected animal model have been evaluated for their capacity to
      induce clearance of the parasite. In the process, a hypothesis was subsequently
      tested regarding the susceptibility of the cured animals to malaria reflected in
      an attenuated parasite load that may be evoked by a protective immune response in
      the host. METHODS: Six weeks old Swiss mice were infected with a lethal
      Plasmodium yoelii (17XL) strain. On appearance of clinical symptoms of malaria,
      these animals were treated with two different GA derivatives and the parasite
      load was monitored over 15-16 days. Drug-treated animals cured of the parasite
      were then re-challenged with a lethal dose of P. yoelii 17XL. Serum samples from
      GA cured mice that were re-challenged with P. yoelii 17XL were examined for the
      presence of antibodies against the parasite proteins using western blot analysis.
      RESULTS: Treatment of P. yoelii 17XL infected mice with GA derivatives showed
      slow recovery from clinical symptoms of the disease. Blood smears from drug
      treated mice indicated a dominance of ring stage parasites when compared to
      controls. Although, P. yoelii preferentially invades normocytes (mature rbcs), in
      drug-treated animals there was an increased invasion of reticulocytes. Cured
      animals exhibited robust protection against subsequent infection and serum
      samples from these animals showed antibodies against a vast majority of parasite
      proteins. CONCLUSIONS: Treatment with GA derivatives blocked the transition from
      ring to trophozoite stage presumably by the inhibition of HSP90 associated
      functions. Persistence of parasite in ring stage leads to robust humoral immune
      response as well as a shift in invasion specificity from normocytes to
      reticulocyte. It is likely that the treatment with the water-soluble GA
      derivative creates an attenuated state (less virulent with altered invasion
      specificity) that persists in the host system, allowing it to mount a robust
      immune response.

PMID- 22361390
TI  - Sarcomeric gene mutations in sudden infant death syndrome (SIDS).
AB  - In developed countries, sudden infant death syndrome (SIDS) represents the most
      prevalent cause of death in children between 1 month and 1 year of age. SIDS is a
      diagnosis of exclusion, a negative autopsy which requires the absence of
      structural organ disease. Although investigators have confirmed that a
      significant percentage of SIDS cases are actually channelopathies, no data have
      been made available as to whether other sudden cardiac death-associated diseases,
      such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of
      SIDS. The presence of a genetic mutation in the sarcomeric protein usually
      affects the force of contraction of the myocyte, whose weakness is compensated
      with progressive hypertrophy and disarray. However, it is unclear whether in the
      most incipient forms, that is, first years of life, the lack of these phenotypes
      still confers a risk of arrhythmogenesis. The main goal of the present study is
      to wonder whether genetic defects in the sarcomeric proteins, previously
      associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS
      cases for the most common genes implicated in HCM in adults. A total of 680
      mutations localised in 16 genes were analysed by semi-automated matrix-assisted
      laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using
      the Sequenom MassARRAY((r)) System. Ten subjects with completely normal hearts
      showed mutated alleles at nine of the genetic variants analysed, and one
      additional novel mutation was detected by conventional sequencing. Therefore, a
      genetic mutation associated with HCM may cause sudden cardiac death in the
      absence of an identifiable phenotype.

PMID- 22361391
TI  - Role of passive immunotherapies in managing infectious outbreaks.
AB  - The historical and current role of passive immunization in managing outbreaks of
      infectious diseases reviewed.

PMID- 22361392
TI  - A mobile phone based alarm system for supervising vital parameters in free moving
      rats.
AB  - BACKGROUND: Study protocols involving experimental animals often require the
      monitoring of different parameters not only in anesthetized, but also in free
      moving animals. Most animal research involves small rodents, in which
      continuously monitoring parameters such as temperature and heart rate is very
      stressful for the awake animals or simply not possible. Aim of the underlying
      study was to monitor heart rate, temperature and activity and to assess
      inflammation in the heart, lungs, liver and kidney in the early postoperative
      phase after experimental cardiopulmonary bypass involving 45 min of deep
      hypothermic circulatory arrest in rats. Besides continuous monitoring of heart
      rate, temperature and behavioural activity, the main focus was on avoiding
      uncontrolled death of an animal in the early postoperative phase in order to
      harvest relevant organs before autolysis would render them unsuitable for the
      assessment of inflammation. FINDINGS: We therefore set up a telemetry-based
      system (Data Science International, DSITM) that continuously monitored the rat's
      temperature, heart rate and activity in their cages. The data collection using
      telemetry was combined with an analysis software (Microsoft excelTM), a webmail
      application (GMX) and a text message-service. Whenever an animal's heart rate
      dropped below the pre-defined threshold of 150 beats per minute (bpm), a
      notification in the form of a text message was automatically sent to the
      experimenter's mobile phone. With a positive predictive value of 93.1% and a
      negative predictive value of 90.5%, the designed surveillance and alarm system
      proved a reliable and inexpensive tool to avoid uncontrolled death in order to
      minimize suffering and harvest relevant organs before autolysis would set in.
      CONCLUSIONS: This combination of a telemetry-based system and software tools
      provided us with a reliable notification system of imminent death. The system's
      high positive predictive value helped to avoid uncontrolled death and facilitated
      timely organ harvesting. Additionally we were able to markedly reduce the drop
      out rate of experimental animals, and therefore the total number of animals used
      in our study. This system can be easily adapted to different study designs and
      prove a helpful tool to relieve stress and more importantly help to reduce animal
      numbers.

PMID- 22361393
TI  - [Research beyond clinical nursing].

PMID- 22361394
TI  - Distribution of metabotropic receptors of serotonin, dopamine, GABA, glutamate,
      and short neuropeptide F in the central complex of Drosophila.
AB  - The central complex is a prominent set of midline neuropils in the insect brain,
      known to be a higher locomotor control center that integrates visual inputs and
      modulates motor outputs. It is composed of four major neuropil structures, the
      ellipsoid body (EB), fan-shaped body (FB), noduli (NO), and protocerebral bridge
      (PB). In Drosophila different types of central complex neurons have been shown to
      express multiple neuropeptides and neurotransmitters; however, the distribution
      of corresponding receptors is not known. Here, we have mapped metabotropic, G
      protein-coupled receptors (GPCRs) of several neurotransmitters to neurons of the
      central complex. By combining immunocytochemistry with GAL4 driven green
      fluorescent protein, we examined the distribution patterns of six different
      GPCRs: two serotonin receptor subtypes (5-HT(1B) and 5-HT(7)), a dopamine
      receptor (DopR), the metabotropic GABA(B) receptor (GABA(B)R), the metabotropic
      glutamate receptor (DmGluR(A)) and a short neuropeptide F receptor (sNPFR1). Five
      of the six GPCRs were mapped to different neurons in the EB (sNPFR1 was not
      seen). Different layers of the FB express DopR, GABA(B)R, DmGluR(A,) and sNPFR1,
      whereas only GABA(B)R and DmGluR(A) were localized to the PB. Finally, strong
      expression of DopR and DmGluR(A) was detected in the NO. In most cases the
      distribution patterns of the GPCRs matched the expression of markers for their
      respective ligands. In some nonmatching regions it is likely that other types of
      dopamine and serotonin receptors or ionotropic GABA and glutamate receptors are
      expressed. Our data suggest that chemical signaling and signal modulation are
      diverse and highly complex in the different compartments and circuits of the
      Drosophila central complex. The information provided here, on receptor
      distribution, will be very useful for future analysis of functional circuits in
      the central complex, based on targeted interference with receptor expression.

PMID- 22361395
TI  - Experiences from having breast cancer and being part of a support group. Notes
      written in diaries by women during radiotherapy.
AB  - OBJECTIVE: The purpose of this study was to examine the experiences of breast
      cancer patients participating in a support group. METHOD: This study explores 28
      stories of women with breast cancer as expressed through written diaries. Diaries
      were written during a 5-week period in parallel with radiotherapy and
      participation in a support group in a hospital. Answers to six open-ended
      evaluative questions concerning the support group were included in the majority
      of the written diaries. A qualitative content analysis was used to identify
      themes. RESULTS: Three themes were constructed during the analysis: "positive
      group development." "Inhibited group development." and "the individual living
      with the disease." Hopes and fears for the future in regards to illness and
      getting better, the value of family and friends, and feelings related to daily
      life with breast cancer such as fatigue and changes in body image were also
      expressed in the diaries. SIGNIFICANCE OF RESULTS: The findings suggest that the
      women with breast cancer found it valuable to be able to share experiences with
      other women in a similar situation in the context of a support group. Being part
      of such a group provided a space and an opportunity for reflection.

PMID- 22361396
TI  - Update on myocarditis.
AB  - Myocarditis is an inflammatory disease of the heart frequently resulting from
      viral infections and/or post-viral immune-mediated responses. It is one of the
      important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed
      on clinical presentation and noninvasive diagnostic methods such as
      cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold
      standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic
      benefits of endomyocardial biopsy results have recently been demonstrated in
      several clinical trials. Although remarkable advances in diagnosis, understanding
      of pathophysiological mechanisms, and treatment of acute myocarditis were gained
      during the last years, no standard treatment strategies could be defined as yet,
      apart from standard heart failure therapy and physical rest. In severe cases,
      mechanical support or heart transplantation may become necessary. There is some
      evidence that immunosuppressive and immunomodulating therapy are effective for
      chronic, virus-negative inflammatory cardiomyopathy. Further investigations by
      controlled, randomized studies are needed to definitively determine their role in
      the treatment of myocarditis.

PMID- 22361397
TI  - Coronary artery disease progression late after successful stent implantation.
AB  - OBJECTIVES: This study sought to define the importance of 5-year coronary artery
      disease (CAD) progression after successful stenting. BACKGROUND: Safety concerns
      regarding first-generation drug-eluting stents mandate 5-year follow-up studies.
      However, only limited data exist on the long-term importance of CAD progression
      relative to late stent-related problems. METHODS: This study followed for 5
      years, 428 consecutive patients randomized to drug-eluting versus bare-metal
      stents with successful stenting documented by freedom from symptoms/events and no
      ischemic perfusion defects (PDs) after 6 months. Rest/stress scintigraphic scans
      were repeated after 60 months. Late events and new PDs in areas remote from
      stented vessels indicated CAD progression. RESULTS: During follow-up, 110 of 428
      (25.7%) patients had 150 clinical events: 43 patients (10%) died, 36 (8.4%)
      suffered a myocardial infarction, and 71 (16.6%) needed repeat revascularization.
      Event rates were lower in remote versus target-vessel areas (9.8% vs. 14.3%, p =
      0.019). Remote myocardial infarction and repeat revascularization accounted for
      46 of 124 (37.1%) nonfatal events and were similar for both stent types. Five
      year scintigraphic studies in patients without follow-up events showed 23.3% new
      PDs, 71% of which were asymptomatic. Remote defects accounted for 37.5% PDs and
      were similar for both stent types. CONCLUSIONS: Even 5 years after stenting,
      target-vessel events and/or new PDs remained more frequent than CAD progression
      assessed by remote events and/or new PDs. Still, remote events accounted for
      almost 40% of all events with a similar rate of additional new PDs, often silent,
      and independent of stent type. This documents the importance of CAD progression
      and stresses the need to differentiate remote from target-vessel events/PDs in
      long-term stent safety studies. (Basel Stent Kosten-Effektivitats Trial [BASKET];
      ISRCTN75663024).

PMID- 22361398
TI  - Disease progression is as important as culprit lesion treatment.

PMID- 22361400
TI  - Allopurinol for heart failure: novel mechanisms.

PMID- 22361399
TI  - Allopurinol acutely increases adenosine triphospate energy delivery in failing
      human hearts.
AB  - OBJECTIVES: This study tested the hypothesis that acute administration of the
      xanthine oxidase (XO) inhibitor allopurinol improves cardiac high-energy
      phosphate concentrations in human heart failure (HF) and increases the rate of
      adenosine triphosphate (ATP) synthesis through creatine kinase (CK), the primary
      myocardial energy reserve. BACKGROUND: Studies of patients and animal models
      implicate impaired myocardial high-energy phosphate availability in HF. The XO
      reaction is a critical terminal step in ATP and purine degradation and an
      important source of reactive oxygen species. Thus, XO inhibition is a potentially
      attractive means to improve energy metabolism in the failing human heart.
      METHODS: We randomized 16 patients with nonischemic cardiomyopathy in a double
      blind fashion to allopurinol (300 mg intravenously) or placebo infusion, 4-to-1,
      the latter for purposes of blinding only. The myocardial concentrations of ATP
      and creatine phosphate (PCr) and the rate of ATP synthesis through CK (CK flux)
      were determined by (31)P magnetic resonance spectroscopy. RESULTS: Allopurinol
      infusion increased mean cardiac PCr/ATP and PCr concentration by ~11% (p < 0.02),
      and mean CK flux by 39% (2.07 +/- 1.27 MUmol/g/s to 2.87 +/- 1.82 MUmol/g/s, p <
      0.007). Calculated cytosolic adenosine diphosphate concentration decreased,
      whereas the free energy of ATP hydrolysis (DeltaG(~ATP)) increased with
      allopurinol. The increased CK flux was disproportionate to substrate changes,
      indicating increased CK enzyme activity. CONCLUSIONS: Intravenous administration
      of the XO inhibitor allopurinol acutely improves the relative and absolute
      concentrations of myocardial high-energy phosphates and ATP flux through CK in
      the failing human heart, offering direct evidence that myofibrillar CK energy
      delivery can be pharmaceutically augmented in the failing human heart.
      (Intravenous Allopurinol in Heart Failure; NCT00181155).

PMID- 22361401
TI  - Bioprosthetic tricuspid valve regurgitation associated with pacemaker or
      defibrillator lead implantation.
AB  - OBJECTIVES: The goal of this study was to determine the impact of transvenous
      pacemaker and defibrillator leads on the incidence of bioprosthetic tricuspid
      valve (BTV) regurgitation compared with BTV patients without a transvalvular
      lead. BACKGROUND: Although concern has been raised regarding the potential
      deleterious effect of permanent transvenous device leads on BTV function, little
      is known about the incidence of prosthetic tricuspid regurgitation (TR) after
      lead placement. METHODS: A retrospective review of 58 patients who underwent BTV
      implantation and subsequently required endocardial pacemaker (n = 52) or
      defibrillator (n = 6) lead implantation across the BTV was conducted. Patient and
      prosthesis characteristics, lead type, and clinical events were collected. The
      incidence and severity of prosthetic TR, determined by Doppler echocardiography,
      was compared with 265 consecutive patients who underwent BTV implantation without
      undergoing subsequent transvalvular device lead implantation. RESULTS: Over a
      mean follow-up of 25 months, in 5 patients (9%) with a transvalvular lead
      significant (moderate or greater) prosthetic TR developed compared with 12
      patients (5%) in the control group (p = 0.20). Kaplan-Meier analysis revealed no
      significant difference in the incidence of TR in BTV patients with and without
      transvalvular leads (p = 0.45). Significant prosthetic TR in patients with and
      without a transvalvular lead more commonly occurred 2 years or later after lead
      or BTV implantation (4 of 5, 80% and 10 of 12, 83%, respectively). CONCLUSIONS:
      Transvalvular device lead implantation in BTV patients was not associated with an
      increased incidence of significant prosthetic TR (p = 0.45). Based on these data,
      transvalvular lead implantation appears to be an acceptable approach for patients
      with a BTV who require permanent pacemaker or defibrillator placement.

PMID- 22361402
TI  - Misleading long post-pacing interval after entrainment of typical atrial flutter
      from the cavotricuspid isthmus.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence and
      mechanism of a misleading long post-pacing interval (PPI) upon entrainment of
      typical atrial flutter (AFL) from the cavotricuspid isthmus (CTI). BACKGROUND: In
      typical AFL, the PPI from entrainment at the CTI is expected to closely match the
      tachycardia cycle-length (TCL). METHODS: Sixty patients with confirmed CTI
      dependent AFL were retrospectively analyzed and grouped into short (<=30 ms) or
      long (>30 ms) PPI-TCL. Thereafter, we prospectively studied 16 patients to
      acquire the PPI-TCL at 4 CTI sites with entrainment at pacing cycle-lengths
      (PCLs) 10 to 40 ms shorter than the TCL. Conduction times during AFL and
      entrainment were compared in 5 segments of the AFL circuit. RESULTS: Eleven
      patients (18%) in the retrospective analysis had a long PPI-TCL after entrainment
      from the CTI. Subjects with long PPI-TCL had similar baseline characteristics but
      greater beat-to-beat TCL variability. In the prospective cohort, PPI-TCL was
      influenced by the difference between PCL and TCL and site of entrainment.
      Conduction delays associated with a long PPI-TCL were located predominantly in
      the segment activated first by the paced orthodromic wave front, and were mainly
      due to local pacing latency, as confirmed by the use of monophasic action
      potential catheters. CONCLUSIONS: A long PPI upon entrainment of typical AFL from
      the CTI is common and due to delayed conduction with entrainment. Whether these
      findings apply to other macro-re-entrant tachycardias warrants further
      investigation.

PMID- 22361403
TI  - Prognostic value of myocardial viability by delayed-enhanced magnetic resonance
      in patients with coronary artery disease and low ejection fraction: impact of
      revascularization therapy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the impact of myocardial
      viability assessment by delayed-enhanced cardiac magnetic resonance (DE-CMR) and
      of revascularization therapy on survival in patients with coronary artery disease
      (CAD) and low ejection fraction (EF). BACKGROUND: Prior studies have shown that
      DE-CMR predicts recovery of left ventricular (LV) dysfunction after
      revascularization. METHODS: The authors prospectively evaluated survival of 144
      consecutive patients (130 males, age 65 +/- 11 years) with CAD and LV dysfunction
      (EF: 24 +/- 7%) undergoing DE-CMR. Eighty-six patients underwent complete
      revascularization of dysfunctional myocardium (79 coronary artery bypass
      grafting, 7 percutaneous coronary intervention), whereas 58 patients remained
      under medical treatment. RESULTS: Over the 3-year median follow-up, 49 patients
      died. Three-year survival was significantly worse in medically treated patients
      with dysfunctional viable than with nonviable myocardium (48% vs. 77% survival, p
      = 0.02). By contrast, in revascularized patients, survival was similar whether
      myocardium was viable or not (88% and 71% survival, respectively, p = NS). Hazard
      of death of viable myocardium remaining under medical treatment versus complete
      revascularization was 4.56 (95% confidence interval [CI]: 1.93 to 10.8). Cox
      multivariate analysis indicated that interaction of revascularization and
      viability provided significant additional value (chi-square test = 13.1, p =
      0.004) to baseline predictors of survival (New York Heart Association functional
      class, wall motion score, and peripheral artery disease). More importantly, in 43
      pairs of propensity score-matched patients, hazard of death (hazard ratio: 2.5
      [95% CI: 1.1 to 6.1], p = 0.02) remained significantly higher for medically
      treated patients rather than for those with fully revascularized viable
      myocardium. CONCLUSIONS: Without revascularization, presence of dysfunctional
      viable myocardium by DE-CMR is an independent predictor of mortality in patients
      with ischemic LV dysfunction. This observation may be useful for pre-operative
      selection of patients for revascularization.

PMID- 22361404
TI  - Myocardial viability imaging: dead or alive?

PMID- 22361405
TI  - Cardiac-specific deletion of SOCS-3 prevents development of left ventricular
      remodeling after acute myocardial infarction.
AB  - OBJECTIVES: The study investigated the role of myocardial suppressor of cytokine
      signaling-3 (SOCS3), an intrinsic negative feedback regulator of the janus kinase
      and signal transducer and activator of transcription (JAK-STAT) signaling
      pathway, in the development of left ventricular (LV) remodeling after acute
      myocardial infarction (AMI). BACKGROUND: LV remodeling after AMI results in poor
      cardiac performance leading to heart failure. Although it has been shown that JAK
      STAT-activating cytokines prevent LV remodeling after AMI in animals, little is
      known about the role of SOCS3 in this process. METHODS: Cardiac-specific SOCS3
      knockout mice (SOCS3-CKO) were generated and subjected to AMI induced by
      permanent ligation of the left anterior descending coronary artery. RESULTS:
      Although the initial infarct size after coronary occlusion measured by
      triphenyltetrazolium chloride staining was comparable between SOCS3-CKO and
      control mice, the infarct size 14 days after AMI was remarkably inhibited in
      SOCS3-CKO, indicating that progression of LV remodeling after AMI was prevented
      in SOCS3-CKO hearts. Prompt and marked up-regulations of multiple JAK-STAT
      activating cytokines including leukemia inhibitory factor and granulocyte colony
      stimulating factor (G-CSF) were observed within the heart following AMI. Cardiac
      specific SOCS3 deletion enhanced multiple cardioprotective signaling pathways
      including STAT3, AKT, and extracellular signal-regulated kinase (ERK)-1/2, while
      inhibiting myocardial apoptosis and fibrosis as well as augmenting antioxidant
      expression. CONCLUSIONS: Enhanced activation of cardioprotective signaling
      pathways by inhibiting myocardial SOCS3 expression prevented LV remodeling after
      AMI. Our data suggest that myocardial SOCS3 may be a key molecule in the
      development of LV remodeling after AMI.

PMID- 22361406
TI  - An unusual case of cyanosis in right ventricular dysplasia in a child.

PMID- 22361407
TI  - Efficacy and safety of dabigatran compared to warfarin in patients with
      paroxysmal, persistent, and permanent atrial fibrillation: results from the RE-LY
      (Randomized Evaluation of Long-Term Anticoagulation Therapy) study.

PMID- 22361408
TI  - Microvolt T-wave alternans testing has no role at present in guiding therapy for
      patients at high risk of ventricular arrhythmias.

PMID- 22361409
TI  - Aortic root mass in multifocal fibrosclerosis.

PMID- 22361410
TI  - Illusory bending of a pursuit target.
AB  - To pursue a small target moving in front of a drifting background, motion vectors
      from the target need to be integrated and segmented from those belonging to the
      background. Smooth pursuit eye movements typically integrate target and
      background directions initially and after some time shift towards the veridical
      target direction. The perceived target direction on the other hand is generally
      stable over time: the target is perceived to move in the same direction as long
      as the motion information maintains the same properties over time. If illusory
      target motion is observed, this tends to be shifted away from the background.
      Here we investigated how initial motion integration and segmentation of such
      stimuli are modulated by direction cues. We presented a small pursuit target
      moving along a straight path, in front of a background moving in a different
      direction. Without a direction cue, initial pursuit was biased towards the
      background direction before shifting towards the veridical target direction. The
      target's perceived direction on the other hand was near veridical. A cue in the
      background direction increased initial pursuit integration but also caused
      perception to behave in a similar way: the target initially had an illusory
      motion component in the background direction and after about 200 ms it was
      perceived to curve towards its veridical direction. This illusion shows that
      during the initial process of segmenting the direction of a pursuit target from
      irrelevant background motion, both pursuit and perception can be erroneously
      influenced by a direction cue and integrate the cued background motion. Both
      modalities corrected this initial integration error as more information about the
      target became available.

PMID- 22361411
TI  - [Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden
      and the MTHFR gene mutation].
AB  - Renal vein thrombosis (RVT) is a rare but potentially serious neonatal disease.
      Its epidemiology and its clinical and biological expression are currently well
      known, but its etiological exploration, like that of venous thromboembolism, is
      increasingly complex. Perinatal risk factors such as prematurity, dehydration,
      and birth asphyxia have lost their direct accountability at the expense of their
      interaction with constitutional disorders of hemostasis. We report a case of RVT
      in a newborn who was a heterozygous carrier of both factor V Leiden and the
      methylene tetrahydrofolate reductase (MTHFR) gene mutation. We recall the
      clinical and epidemiological characteristics. A search for inborn blood
      coagulation disorders should be systematic in the newborn infant with venous
      thrombosis because of the risk of recurrence, taking into account perinatal
      factors and maternal thrombophilia (especially if RVT is established during the
      prenatal period).

PMID- 22361412
TI  - A case of sinonasal teratocarcinosarcoma treated with surgery and post-operative
      intensity-modulated radiotherapy (IMRT).
AB  - Sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive malignant
      neoplasm, which has poor prognosis. SNTCS is histologically characterized by the
      combination of one or more epithelial elements and mesenchymal components. We
      report a 59-year-old man with SNTCS involving right maxillary and ethmoid
      sinuses. He complained of numbness of the right cheek for 1 month. Computed
      tomography and magnetic resonance imaging revealed soft tissue filling the right
      maxillary and ethmoid sinuses, protruding into the nasal cavity. Tumor was
      removed with Denker rhinotomy, and post-operative intensity-modulated radiation
      therapy (IMRT: 64Gy in 32 fractions) was performed. Follow-up examination for 2
      years after the IMRT has shown no evidence of recurrence or metastasis. IMRT is a
      new type of conformal radiotherapy that is based on the use of non-uniform
      radiation beam intensities. IMRT can achieve optimal dose distributions and may
      improve the clinical outcomes dramatically with minimal complications. This
      report describes this patient's clinical course, etiology, diagnosis and
      management of SNTCS, and the advantage of IMRT in the treatment of SNTCS.

PMID- 22361413
TI  - Usefulness and pitfall of Narrow band imaging combined with magnifying endoscopy
      for detecting an unknown head and neck primary site with cervical lymph node
      metastasis.
AB  - OBJECTIVE: Cervical nodal metastasis from clinically undetectable primary
      squamous cell carcinoma (SCC) accounts for 1-2% of head and neck malignancies. We
      retrospectively evaluate the ability of Narrow band imaging combined with
      magnifying endoscopy (NBI-ME) to detect the primary sites of superficial SCC in
      the head and neck region. METHODS: This was a report of 11 patients. We performed
      with NBI-ME to detect unknown primary sites in the head and neck. RESULTS: Among
      11 patients, primary sites were detected in eight. Primary sites were detected in
      the head and neck in 6 (54.5%) of 11 patients on NBI-ME, all 6 primary lesions
      were a flat lesion. Two patients in whom primary lesions could not be detected on
      NBI-ME, one had submucosal tumor like lesion, the other featured by a detectable
      primary lesion 19 months after neck dissection. CONCLUSION: NBI-ME can be
      recommended as an essential procedure for the detection of primary lesions in
      patients with primary unknown cervical lymph node metastasis.

PMID- 22361414
TI  - Perception of Mandarin Chinese with cochlear implants using enhanced temporal
      pitch cues.
AB  - A cochlear implant (CI) signal processing strategy named F0 modulation (F0mod)
      was compared with the advanced combination encoder (ACE) strategy in a group of
      four post-lingually deafened Mandarin Chinese speaking CI listeners. F0 provides
      an enhanced temporal pitch cue by amplitude modulating the multichannel
      electrical stimulation pattern at the fundamental frequency (F0) of the incoming
      speech signal. Word and sentence recognition tests were carried out in quiet and
      in noise. The responses for the word-recognition test were further segmented into
      phoneme and tone scores. Off-line implementations of ACE and F0mod were used, and
      electrical stimulation patterns were directly streamed to the CI subject's
      implant. To focus on the feasibility of enhanced temporal cues for tonal language
      perception, idealized F0 information that was extracted from speech tokens in
      quiet was used in the F0mod processing of speech-in-noise mixtures. The results
      indicated significantly better lexical tone perception with the F0mod strategy
      than with ACE for the male voice (p<0.05). No significant differences in sentence
      recognition were found between F0mod and ACE.

PMID- 22361415
TI  - Variations of the iliac and pelvic venous systems with special attention to the
      drainage patterns of the ascending lumbar and iliolumbar veins.
AB  - The anatomy of the inferior vena cava (IVC) and common, external and internal
      iliac veins (CIV, EIV, IIV respectively) was examined in 59 embalmed adult human
      cadavers of Caucasian origin. In the present study, we focus our attention on the
      drainage patterns of the ascending lumbar and iliolumbar veins (ALV, ILV) when
      there are variations in the major pelvic veins by highlighting and describing the
      variations themselves. The above patterns, when no variations exist, have already
      been reported. Among the 59 cadavers, nine (9/59, 15.3%) presented anomalies of
      the major pelvic veins, as follows: anomalous drainage of both EIV and IIV in
      8.5% of the specimens (5/59, Type I); variations of the IVC in 3.4% (2/59, Type
      II); duplication of the IIV (1/59=1.7%, Type III); anastomotic branch between the
      right IIV and the left CIV (1/59=1.7%, Type IV). ALV drained either into the CIV
      (8/18 sides, 44.4%) or in EIV (5/18 sides, 27.8%), while absence of ILV was the
      most frequent pattern (8/18 sides, 44.4%). A common trunk, joining the two veins,
      was observed in 5/18 sides (27.8%). Those drainage patterns were in accordance
      with the ones discovered in our previous study. In Type I the two veins always
      drained into the EIV. Knowledge of the surgical anatomy of all studied veins may
      prevent injury to these veins during operations in the retroperitoneal space and
      pelvis or malposition of venous catheters placed from the groin.

PMID- 22361417
TI  - Tackling hepatitis C in Australia: the third national strategy.

PMID- 22361416
TI  - Conserved requirement for DEAD-box RNA helicase Gemin3 in Drosophila oogenesis.
AB  - BACKGROUND: DEAD-box RNA helicase Gemin3 is an essential protein since its
      deficiency is lethal in both vertebrates and invertebrates. In addition to
      playing a role in transcriptional regulation and RNA silencing, as a core member
      of the SMN (survival of motor neurons) complex, Gemin3 is required for the
      biogenesis of spliceosomal snRNPs (small nuclear ribonucleoproteins), and axonal
      mRNA metabolism. Studies in the mouse and C. elegans revealed that loss of Gemin3
      function has a negative impact on ovarian physiology and development. FINDINGS:
      This work reports on the generation and characterisation of gemin3 mutant
      germline clones in Drosophila adult females. Gemin3 was found to be required for
      the completion of oogenesis and its loss led to egg polarity defects, oocyte
      mislocalisation, and abnormal chromosome morphology. Canonical Cajal bodies were
      absent in the majority of gemin3 mutant egg chambers and histone locus bodies
      displayed an atypical morphology. snRNP distribution was perturbed so that on
      gemin3 loss, snRNP cytoplasmic aggregates (U bodies) were only visible in wild
      type. CONCLUSIONS: These findings establish a conserved requirement for Gemin3 in
      Drosophila oogenesis. Furthermore, in view of the similarity to the phenotypes
      described previously in smn mutant germ cells, the present results confirm the
      close functional relationship between SMN and Gemin3 on a cellular level.

PMID- 22361418
TI  - Supply chain problems for Chagas disease treatment.

PMID- 22361419
TI  - Moxifloxacin for tuberculosis.

PMID- 22361420
TI  - Moxifloxacin for tuberculosis.

PMID- 22361422
TI  - MDR tuberculosis and non-compliance with therapy.

PMID- 22361424
TI  - Resistance after selective decontamination.

PMID- 22361425
TI  - Resistance after selective decontamination.

PMID- 22361428
TI  - Selective digestive decontamination and antibiotic resistance.

PMID- 22361429
TI  - Antibiotics obtained without a prescription in Europe.

PMID- 22361430
TI  - Timothy Walsh: introducing the world to NDM-1.

PMID- 22361431
TI  - Disseminated cutaneous Mycobacterium chelonae.

PMID- 22361432
TI  - Deep venous thrombosis in children with musculoskeletal infections: the clinical
      evidence.
AB  - BACKGROUND: Clinical manifestations of deep venous thrombosis (DVT) tend to
      overlap with those of deep-seated musculoskeletal infections (MSIs).
      Consequently, the incidence of DVT as a complication of MSI may be
      underestimated. The objective of this study was to evaluate the incidence,
      clinical features, and outcomes of MSI-related DVT in children. METHODS: We
      systematically reviewed relevant studies retrieved from PubMed and Scopus
      databases. RESULTS: Overall, 93 children with MSIs who developed DVT were
      identified from 28 retrospective studies. The majority were boys. Osteomyelitis
      was the most frequent MSI (69/74, 93%). Staphylococcus aureus was the predominant
      pathogen (83/93, 89%); 61% of these isolates were methicillin-resistant S. aureus
      (MRSA). Pulmonary involvement, presumably due to septic emboli, was observed in
      65% of the included children. Four children died due to multiple organ failure
      and two due to respiratory distress. In two of the three studies providing
      comparative data, MRSA infections were observed significantly more frequently in
      children who developed DVT compared to those who did not. Yet, the respective
      differences observed for methicillin-susceptible S. aureus (MSSA) infections were
      non-significant in these three studies. CONCLUSIONS: Despite the inclusion of
      many case reports and the retrospective design of the evaluated studies, our
      findings suggest that boys seem to be more frequently affected by MSIs
      complicated by DVT. Moreover, MRSA seems to be more frequently associated with
      DVT compared to MSSA. Pulmonary involvement appears to be a frequent
      complication. Prospective studies are needed in order to further clarify this
      issue.

PMID- 22361434
TI  - Injuries before and after deployments to Afghanistan and Iraq.
AB  - OBJECTIVE: To examine outpatient injuries before and after deployments of
      elements of the 10th Mountain Division to Afghanistan (n = 505 men) and the 1st
      Cavalry Division to Iraq (n = 3242 men). STUDY DESIGN: Observational. METHODS:
      The military units provided a list of deployed soldiers, and soldiers' outpatient
      medical encounters were obtained from the Defense Medical Surveillance System.
      Cumulative injury incidence was examined for two consecutive 90-day periods
      before the deployments (Periods 1-2) and two consecutive 90-day periods after the
      deployments (Periods 3-4). RESULTS: Both groups showed post-deployment increases
      in the overall incidence of injury (Afghanistan group = 14.1%, 14.1%, 16.4,
      23.4%; Iraq Group = 15.1%, 12.4%, 35.4%, 43.4%; Periods 1-4, respectively).
      Soldiers with pre-deployment injuries were 1.4-3.0 times more likely to
      experience post-deployment injuries. CONCLUSIONS: This study found a post
      deployment increase in the incidence of outpatient injury. Also, soldiers with
      pre-deployment injuries were more likely to experience post-deployment injuries.

PMID- 22361433
TI  - Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity
      in cancer-induced skeletal muscle wasting.
AB  - Cancer cachexia is a highly debilitating paraneoplastic disease observed in more
      than 50% of patients with advanced cancers and directly contributes to 20% of
      cancer deaths. Loss of skeletal muscle is a defining characteristic of patients
      with cancer cachexia and is associated with poor survival. The present study
      reveals the involvement of a myogenic transcription factor Myocyte Enhancer
      Factor (MEF) 2C in cancer-induced skeletal muscle wasting. Increased skeletal
      muscle mRNA expression of Suppressor of Cytokine Signaling (Socs) 3 and the IL-6
      receptor indicative of active IL-6 signaling was seen in skeletal muscle of mice
      bearing the Colon 26 (C26) carcinoma. Loss of skeletal muscle structural
      integrity and distorted mitochondria were also observed using electron
      microscopy. Gene and protein expression of MEF2C was significantly downregulated
      in skeletal muscle from C26-bearing mice. MEF2C gene targets myozenin and
      myoglobin as well as myokinase were also altered during cachexia, suggesting
      dysregulated oxygen transport capacity and ATP regeneration in addition to
      distorted structural integrity. In addition, reduced expression of calcineurin
      was observed which suggested a potential pathway of MEF2C dysregulation.
      Together, these effects may limit sarcomeric contractile ability and also
      predispose skeletal muscle to structural instability; associated with muscle
      wasting and fatigue in cachexia.

PMID- 22361435
TI  - An investigation of body image concern and the effects of sociocultural factors
      among U.K. first year university students.

PMID- 22361437
TI  - Dental practice populations: the effect of distance on the most socially deprived
      communities accessing dental care in the North East of England.

PMID- 22361438
TI  - 'Decipio': examining Virchow in the context of modern 'democracy'.
AB  - More than 100 years ago Rudolf Virchow advocated for enhanced democracy and
      socioeconomic reforms in order that the state could empower people to achieve
      better health. With reference to these now famous assertions this article traces
      the promises and pit-falls of democracy from ancient Greece to neo-liberal
      economies, to ascertain if the democratic state is indeed the ideal mechanism for
      promoting public health. In the end we conclude that contemporary western
      political systems are not rooted in the interest of the people, but are rather
      deceptive forces of branding designed to promote underlining agendas. This
      'decipractic' (decipo = to deceive) system of politics demands a vigilant
      analysis and response from those in the health and academic communities to ensure
      that governments can be a mechanism for positive change in the public's interest.

PMID- 22361439
TI  - Indium tin oxide nanowhisker morphology control by vapour-liquid-solid glancing
      angle deposition.
AB  - A new growth technique for indium tin oxide nanowhiskers with increased control
      over feature size and spacing is reported. The technique is based on a unique
      combination of self-catalysed vapour-liquid-solid (VLS) growth and glancing angle
      deposition (GLAD). This VLS-GLAD technique provides enhanced control over
      nanowhisker morphology as the effect of typical VLS growth parameters (e.g. flux
      rate, temperature) is amplified at large deposition angles characteristic of
      GLAD. Spatial modulation of the collimated growth flux controls trunk width,
      number and orientation of branches, and overall nanowhisker density. Here we
      report the influence of growth conditions (including deposition angle, flux rate,
      nominal pitch and substrate temperature) on nanowhisker morphology, with specific
      focus on the effect of large deposition angles. Sheet resistance and transmission
      of the films were measured to characterize their performance as transparent
      conductive oxides. Hybrid nanostructured films grown in this study include high
      surface area nanowhiskers protruding from a conductive film, ideal for
      transparent conductive electrode applications.

PMID- 22361440
TI  - Acute pancreatitis associated with H1N1 influenza during 2009 pandemic: a case
      report.
AB  - The relationship between viral infections and acute pancreatitis (AP) is not well
      defined and universally accepted. Although an association is debated due to lack
      of solid evidence, a vast number of case reports suggest a possible
      interrelation. Influenza A virus is one of the most common infectious pathogens
      in humans but the incidence of subclinical or overt AP during the course of flu
      is unknown. We report a case of AP, which occurs shortly after a H1N1 infection
      during the pandemic in 2009.

PMID- 22361442
TI  - Radiofrequency ablation associated to mucosal resection in the oesophagus:
      experience in a single centre.
AB  - Endoscopic resection (EMR) and radiofrequency ablation (RFA) form part of the
      treatment of Barrett's oesophagus (BO), dysplasia, superficial adenocarcinoma
      (OAC) associated with BO. PATIENTS AND METHODS: Between June 2008 and April 2011,
      34 patients underwent treatment with RFA (HALO system((r))), in a tertiary
      centre. For the study, patients were divided into two groups. Group 1 (16
      patients of average 60 years old; 14 men, two women) received EMR and RFA. Group
      2 (18 patients averaging 59 years age; 14 men, four women) received RFA without
      EMR in the year preceding the RFA. RESULTS: In group 1, high grade dysplasia
      (HGD) was eradicated in 12 cases (92%), low grade dysplasia (LGD) in three cases
      (100%). Complete response occurred in nine cases (56%), partial response in 100%
      of cases. Mean follow-up was 15 months. In group 2, HGD was eradicated in one
      patient (100%), LGD in three patients (64%). A complete response was achieved in
      eight patients, partial response in four cases (77%). Mean follow-up was 10
      months. The complication rate for groups 1 and 2 was of 18% and 10% respectively.
      No complication prevented completion of treatment or continued monitoring.
      Recurrence was evaluated to 5% in both groups. CONCLUSION: RFA associated with
      EMR is feasible, offering probably better results and a very important advantage:
      a more complete histology before follow-up. Our results show effective treatment
      of BO and associated dysplasia with a low rate of complication. Nevertheless,
      when new techniques of BO ablation are used, the need to obtain histology before
      treatment should not be forgotten.

PMID- 22361441
TI  - Clinical usefulness of microsatellite instability test in Korean young patients
      with high-risk features associated with adenoma.
AB  - The aim of this study was to determine the correlation between microsatellite
      instability (MSI) and young age in patients with advanced colorectal adenomas. We
      retrospectively analyzed young patients (<= 40 years of age) with advanced
      adenomas (n=84) between January 1996 and December 2006. We randomly selected the
      control group as patients >= 50 years of age with advanced adenomas (n=84) during
      the same time period. Of these patients, the MSI test and MLH1
      immunohistochemistry were performed in the available tissue samples from patients
      with advanced adenomas. The number of patients who had the two tests was 52 in
      the young group and 49 in the old group. The monomorphic nature of the BAT26
      panel for MSI analysis was used without comparison of normal tissue. MSI was
      detected in three young patients (n=52) and none of the old patients (n=49).
      There was no statistical difference between the two groups (P=0.243). All three
      young patients with MSI had a strong family history of colorectal cancer. MSI
      analysis was not a useful method of screening for HNPCC in young patients with
      advanced colorectal adenoma, at least in cases without a family history of
      colorectal cancer.

PMID- 22361443
TI  - Sensory phenomena associated with repetitive behaviors in obsessive-compulsive
      disorder: an exploratory study of 1001 patients.
AB  - A substantial number of patients with obsessive-compulsive disorder (OCD) report
      compulsions that are preceded not by obsessions but by subjective experiences
      known as sensory phenomena. This study aimed to investigate the frequency,
      severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD
      patients with and without sensory phenomena in terms of clinical characteristics.
      We assessed 1,001 consecutive OCD patients, using instruments designed to
      evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level
      of insight and presence/severity of sensory phenomena. All together, 651 (65.0%)
      subjects reported at least one type of sensory phenomena preceding the repetitive
      behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had
      musculoskeletal sensations, 519 (79.7%) had externally triggered "just-right"
      perceptions, 176 (27.0%) presented internally triggered "just right," 144 (22.1%)
      had an "energy release," and 240 (36.9%) patients had an "urge only" phenomenon.
      Sensory phenomena were described as being as more severe than were obsessions by
      102(15.7%) patients. Logistic regression analysis showed that the following
      characteristics were associated with the presence of sensory phenomena: higher
      frequency and greater severity of the symmetry/ordering/arranging and
      contamination/washing symptom dimensions; comorbid Tourette syndrome, and a
      family history of tic disorders. These data suggest that sensory phenomena
      constitute a poorly understood psychopathological aspect of OCD that merits
      further investigation.

PMID- 22361444
TI  - A detailed association analysis between the tryptophan hydroxylase 2 (TPH2) gene
      and autism spectrum disorders in a Japanese population.
AB  - We conducted a detailed association analysis between the tryptophan hydroxylase 2
      gene and autism spectrum disorders in a Japanese population using 19 markers,
      including tagging single nucleotide polymorphisms and a novel missense variation,
      p.R225Q, identified through exon resequencing. However, we failed to obtain
      supportive evidence for an association.

PMID- 22361445
TI  - Schizotypy and subjective well-being in university students.
AB  - One hundred and thirty-nine university students completed measures of schizotypy
      and subjective well-being (SWB). Inverse associations were found between
      schizotypy and SWB scores. These results provide evidence that diminished SWB is
      characteristic along the schizophrenia continuum. Further research is required to
      determine the mechanisms by which schizotypal individuals experience reduced life
      satisfaction.

PMID- 22361446
TI  - Associations between cognitive biases and domains of schizotypy in a non-clinical
      sample.
AB  - Schizotypy is a non-clinical manifestation of the same underlying biological
      factors that give rise to psychotic disorders (Claridge and Beech, 1995).
      Research on normative populations scoring high on schizotypy is valuable because
      it may help elucidate the predisposition to schizophrenia (Jahshan and Sergi,
      2007) and because performance is not confounded by issues present in
      schizophrenia samples. In the current study, a Confirmatory Factor Analysis was
      conducted using several comprehensive measures of schizotypy. As expected and
      replicating prior research, a four-factor model of schizotypy emerged including a
      positive, a negative, a cognitive disorganization, and an impulsive nonconformity
      factor. We also evaluated how each factor related to distinct cognitive biases.
      In support of hypotheses, increased self-certainty, decreased theory of mind, and
      decreased source memory were associated with higher scores on the positive
      factor; decreased theory of mind was associated with higher scores on the
      negative factor; and increased self-certainty was associated with greater
      impulsive nonconformity. Unexpectedly, decreased self-certainty and increased
      theory of mind were associated with greater cognitive disorganization, and
      decreased source memory was associated with greater impulsive nonconformity.
      These findings offer new insights by highlighting cognitive biases that may be
      risk factors for psychosis.

PMID- 22361448
TI  - Adjuvant chemotherapy for breast cancer patients: patients' expectations and
      physicians' attitudes.
AB  - OBJECTIVE: Findings show that there is a certain degree of refusal on the part of
      breast cancer patients to undergo adjuvant therapy. Accordingly, the major goals
      of the study were, first, to learn more about the beliefs of breast cancer
      patients in regard to adjuvant therapy; second, to find out about the sources of
      the patients' beliefs; and third, to learn about the attitudes of oncologists
      concerning the same aspects of adjuvant therapy to which the patients' beliefs
      referred. METHOD: The participants were 92 breast cancer patients (mean age 61.2)
      and 57 doctors of both genders specialized in oncology or affiliated domains.
      Both groups were administered questionnaires referring to goals of adjuvant
      treatment, the chances of attaining these goals, side effects, and difficulty of
      the treatment. Doctors were specifically asked about the views they thought
      proper to communicate to patients in regard to the mentioned issues. Patients
      were also asked about whether they had doubts about the treatment and sources of
      information. RESULTS: The findings showed disparities between the views of
      patients and doctors in regard to goals, chances of attainment, side effects, and
      difficulty of treatment. Patients endorsed more goals than doctors and tended to
      assign to them lower chances of attainment. Doctors were divided in their views
      about whether to communicate the side effects and difficulties. SIGNIFICANCE OF
      RESULTS: The results reveal the importance of outlining goals for patients
      undergoing adjuvant treatment and the disagreements between doctors about what
      should be communicated to patients, and highlight the complexity of providing to
      patients information that is both scientifically correct and emotionally helpful.

PMID- 22361447
TI  - High ethanol and acetaldehyde impair spatial memory in mouse models: opposite
      effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory.
AB  - Aldehyde dehydrogenase 2 deficiency may directly contribute to excess
      acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates
      some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be
      involved in the alteration of attention and memory. We have chosen Aldh2-knockout
      (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects
      of EtOH and AcH on spatial memory and to compare the possible relationship
      between genetic deficiency and memory using two behavioral assessments. Mice were
      trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally
      on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris
      water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors,
      indicating memory impairment on the eight-arm radial maze (RAM) for all the mice
      studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE
      KO mice, but not WT mice. We found similar effects of EtOH on the MWM
      performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram
      EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The
      2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting
      an AcH effect. Furthermore, time spent on the probe trial was shorter in mice
      that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly,
      while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest
      that high EtOH and AcH impair spatial memory in mice, while lower doses do not
      have consistent memory effects. In addition, we conclude that genetic differences
      might underlie some of EtOH's effects on memory.

PMID- 22361449
TI  - HIV treatment adherence, patient health literacy, and health care provider
      patient communication: results from the 2010 AIDS Treatment for Life
      International Survey.
AB  - BACKGROUND: Little is known about patients' health literacy regarding
      antiretroviral therapy (ART) adherence and drug resistance and patient-provider
      communication about these topics. DESIGN AND METHODS: The AIDS Treatment for Life
      International Survey was a multicountry cross-sectional study (January-March
      2010) including 2035 HIV-infected adults. A 40-minute interview was conducted
      using a standardized self-report adherence questionnaire. RESULTS: Overall, 57%
      of patients reported a 30-day recall of 100% adherence (Latin America: 89%;
      Africa: 73% vs North America: 45% and Asia Pacific: 47%; P < .01). Overall, 18%
      identified HIV drug resistance as a "good thing" in North America (35%) and
      Africa (24%). Only 71% said their health care providers had offered practical
      recommendations about adherence, 62% of the patients in North America and 80% in
      Latin America and Africa. CONCLUSIONS: Optimal ART adherence remains a challenge
      globally. There is a critical need to improve patient-provider communication
      about the importance of ART adherence and its benefits for patient's health.

PMID- 22361450
TI  - Orthorexia nervosa: a frequent eating disordered behavior in athletes.
AB  - Striving for enhancing athletic performance, many sportsmen undergo rigid dietary
      habits, which could lead to eating disorders (EDs) or Orthorexia Nervosa (ON), a
      psychopathological condition characterized by the obsession for high quality
      food. The aim of the study was to examine the occurrence of ON in athletes and to
      verify the relationship between ON and EDs. Five-hundred-seventy-seven athletes
      and 217 matched controls were administered the following tests: ORTO-15, Eating
      Attitude Test 26 (EAT-26), Body Uneasiness Test (BUT) and Yale-Brown-Cornell
      Eating Disorder Scale (YBC-EDS). High positivity to ORTO-15 (28%) and EAT-26
      (14%) emerged in athletes, whereas a high rate of BUT positivity was evident
      among controls (21%). Multivariate logistic regression analysis revealed that
      independent predictors of ON are previous dieting, age, positivity to YBC-EDS,
      positivity to EAT-26, competition level, and number of YBC-EDS preoccupations and
      rituals. Sharing many features with both EDs and Obsessive-Compulsive Spectrum,
      ON represents a crossroad between these pathologic conditions and might
      compromise the health state of an athlete. Therefore, coaches should consider
      important to detect symptoms of EDs and ON in their athletes.

PMID- 22361451
TI  - Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis.
AB  - BACKGROUND: Substantial efforts have been deployed in the past decade to identify
      the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized
      here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level
      and promote neurodegeneration. METHODS: We sequenced the coding exons of SORT1 in
      a cohort of 112 unrelated individuals with familial ALS. We also tested for
      aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing
      six different ALS-associated TARDBP mutations. RESULTS: We identified one unique
      missense and two unique silent mutations in our cohort. None are predicted to
      have functional effects. No aberrant SORT1 splicing event was observed.
      CONCLUSIONS: SORT1 mutations are not a common cause of familial ALS, and the
      influence of TARDBP mutations on SORT1 splicing still needs to be clarified.

PMID- 22361452
TI  - Congenital abnormalities in Japanese patients with Menkes disease.
AB  - Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born
      infants with MNK is 2.8 per million live births in Japan. The aim of this study
      was to observe congenital malformations (CMs) in MNK patients. Subjects comprised
      35 Japanese male patients with classical MNK who received copper histidine
      treatment. Patient clinical data were obtained anonymously from medical records
      or medical record summaries by pediatrician's retrospective review through a
      survey. We observed 21 different CMs in 14 patients. Eight of these had a single
      CM, while six had multiple CMs. The most frequent CM was higher arched palate
      with other CMs found in five patients. There was no relationship between CMs and
      mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also
      significantly lower in MNK patients with CMs (P<0.05), compared to those without
      CMs, even though there was no significant difference of age onset, age at
      diagnosis and age at start of treatment with copper histidine between both groups
      of patients. Sudden death occurred in three MNK patients with CMs only: two with
      congenital heart disease, and one with microphallus.

PMID- 22361453
TI  - Exacerbation of idiopathic paroxysmal kinesigenic dyskinesia in remission state
      caused by secondary hypoparathyroidism with hypocalcemia after thyroidectomy:
      evidence for ion channelopathy.
AB  - Most reported cases of paroxysmal kinesigenic dyskinesia (PKD) are idiopathic or
      familial; however, hypoparathyroidism is another unusual cause of secondary PKD.
      The pathomechanism of PKD remains poorly understood, and the association between
      idiopathic and secondary PKD remains an enigma, and has yet to be clearly
      elucidated. We recently encountered a patient with idiopathic PKD whose symptoms
      were aggravated by secondary hypoparathyroidism with hypocalcemia after having
      undergone a thyroidectomy. The patient's paroxysms were ameliorated by the
      normalization of serum calcium levels. The results discussed herein may provide
      support for the hypothesis that PKD is associated with neuronal ion regulation.

PMID- 22361454
TI  - Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors
      for chemoprevention of cancer.
AB  - The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic
      pyrazole derivatives fused with steroidal structure for chemoprevention of cancer
      is reported herein. All compounds were interestingly less toxic than the
      reference drug (Cyproterone((r))). The aromatase inhibitory activities of these
      compounds were much more potent than the lead compound resveratrol, which has an
      IC(50) of 80 MUM. In addition, all the compounds displayed potent quinone
      reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed
      via the determination of their LD(50). The aromatase and quinone reductase-2
      inhibitors resulting from this study have potential value in the treatment and
      prevention of cancer.

PMID- 22361455
TI  - Optimization of extracellular glucan production from Pleurotus eryngii and its
      impact on angiogenesis.
AB  - Pleurotus eryngii, an edible mushroom with therapeutic potential was optimized
      using response surface methodology of four-factor Box-Behnken design for maximum
      mycelial biomass and extracellular glucan (EPS) production. The model predicts to
      gain a maximal mycelial biomass and extracellular polysaccharide at 39.4 g/l;
      36.04 g/l of glucose, 8.27 g/l; 7.51 g/l of yeast extract, pH 6.99; 7.07 and
      temperature 26.2 degrees C; 25.84 degrees C, respectively. The validation
      experiments showed that the model was significant and in close agreement with the
      model prediction. The evaluation of extracellular polysaccharide on angiogenesis
      by ex vivo CAM assay showed that there was significant inhibition in neo
      vascularization.

PMID- 22361456
TI  - Interaction of 3'-azido-3'-deamino daunorubicin with DNA: multispectroscopic and
      molecular modeling.
AB  - In this paper, 3'-azido-3'-deamino daunorubicin (ADNR) was synthesized and the
      interaction of ADNR and calf thymus DNA (ctDNA) was investigated for the first
      time by using multi-spectroscopic techniques and molecular modeling study in
      vitro under simulated physiological conditions. Hypochromicity of the absorption
      spectra of ADNR were observed in the presence of ctDNA, and the fluorescence of
      ADNR was strongly quenched through static mechanism with the addition of ctDNA.
      Moreover, the fluorescence polarization was increased when ctDNA was added. From
      the experimental results, conclusion can be drawn that the binding mode of ADNR
      with ctDNA was an intercalative binding, and the calculated thermodynamic
      parameters suggested that the binding of ADNR to ctDNA was driven mainly by
      hydrogen bonding force. Furthermore, the results obtained from computational
      modeling further proved the experimental results obtained from spectroscopic
      investigations.

PMID- 22361457
TI  - High-resolution melting analysis of the single nucleotide polymorphism hot-spot
      region in the rpoB gene as an indicator of reduced susceptibility to rifaximin in
      Clostridium difficile.
AB  - Clostridium difficile, a Gram-positive, spore-forming, anaerobic bacterium, is
      the main causative agent of hospital-acquired diarrhoea worldwide. In addition to
      metronidazole and vancomycin, rifaximin, a rifamycin derivative, is a promising
      antibiotic for the treatment of recurring C. difficile infections (CDI). However,
      exposure of C. difficile to this antibiotic has led to the development of
      rifaximin-resistance due to point mutations in the beta-subunit of the RNA
      polymerase (rpoB) gene. In the present study, 348 C. difficile strains with known
      PCR-ribotypes were investigated for respective single nucleotide polymorphisms
      (SNPs) within the proposed rpoB hot-spot region by using high-resolution melting
      (HRM) analysis. This method allows the detection of SNPs by comparing the altered
      melting behaviour of dsDNA with that of wild-type DNA. Discrimination between
      wild-type and mutant strains was enhanced by creating heteroduplexes by mixing
      sample DNA with wild-type DNA, leading to characteristic melting curve shapes
      from samples containing SNPs in the respective rpoB section. In the present
      study, we were able to identify 16 different rpoB sequence-types (ST) by
      sequencing analysis of a 325 bp fragment. The 16 PCR STs displayed a total of 24
      different SNPs. Fifteen of these 24 SNPs were located within the proposed 151 bp
      SNP hot-spot region, resulting in 11 different HRM curve profiles (CP). Eleven
      SNPs (seven of which were within the proposed hot-spot region) led to amino acid
      substitutions associated with reduced susceptibility to rifaximin and 13 SNPs
      (eight of which were within the hot-spot region) were synonymous. This
      investigation clearly demonstrates that HRM analysis of the proposed SNP hot-spot
      region in the rpoB gene of C. difficile is a fast and cost-effective method for
      the identification of C. difficile samples with reduced susceptibility to
      rifaximin and even allows simultaneous SNP subtyping of the respective C.
      difficile isolates.

PMID- 22361458
TI  - Corynebacterium pseudodiphtheriticum septic arthritis secondary to intra
      articular injection--a case report and literature review.
AB  - This is believed to be the first report of a case of septic arthritis, secondary
      to intra-articular injection, caused by Corynebacterium pseudodiphtheriticum - a
      skin commensal micro-organism. Review of the literature highlights the rarity of
      this pathogen in osteoarticular infections and a potential for delayed diagnosis
      and inadequate treatment due to subtle initial presentation.

PMID- 22361460
TI  - Involvement of efflux mechanisms in biocide resistance of Campylobacter jejuni
      and Campylobacter coli.
AB  - Active efflux has an important role in the antimicrobial resistance of
      Campylobacter jejuni and Campylobacter coli. The effects of two putative efflux
      pump inhibitors (EPIs), phenylalanine-arginine beta-naphthylamide and 1-(1
      naphthylmethyl)-piperazine, and the effects of inactivation of the cmeB,cmeF and
      cmeR genes on resistance to a broad range of antimicrobials were studied using
      the broth microdilution method. The antimicrobials tested in C. jejuni and C.
      coli were the biocides triclosan, benzalkonium chloride, chlorhexidine diacetate,
      cetylpyridinium chloride and trisodium phosphate, along with the anionic
      surfactant SDS and the antibiotics erythromycin and ciprofloxacin. Both EPIs
      partially reversed the resistance to all of these antimicrobials. Differences
      between these EPIs were seen for substrate preference and reductions in MIC. The
      MICs of the antimicrobials were reduced in the cmeB and cmeF mutants and
      increased in the cmeR mutant, with few exceptions. Both of these putative EPIs
      further decreased the MICs of the antimicrobials in these mutant strains. These
      data confirm that active efflux is an important mechanism in biocide resistance
      in C. jejuni and C. coli. At least one non-CmeABC efflux system or reduced uptake
      is responsible for resistance to biocides.

PMID- 22361459
TI  - Non-thermal argon plasma is bactericidal for the intracellular bacterial pathogen
      Chlamydia trachomatis.
AB  - Non-thermal plasma (NTP) is a flow of partially ionized argon gas at an ambient
      macroscopic temperature and is microbicidal for bacteria, viruses and fungi.
      Viability of the Gram-negative obligate intracellular bacterial parasite
      Chlamydia trachomatis and its host cells was investigated after NTP treatment.
      NTP treatment of C. trachomatis extracellular elementary bodies (EBs) diminished
      the concentration of infectious bacteria by a factor of 9*10(4), as established
      by the parallel infection of murine fibroblast McCoy cells with treated and
      control EBs. NTP treatment of infected McCoy cells caused disruption of membrane
      restricted vacuoles (inclusions), where C. trachomatis intracellular reticulate
      bodies (RBs) multiply, and a 2*10(6)-fold reduction in the concentration of
      infectious bacteria. When the samples were covered with magnesium fluoride glass
      to obstruct plasma particles and UV rays alone were applied, the bactericidal
      effect was reduced 1.4*10(1)-fold and 5*10(4)-fold for EBs and RBs, respectively.
      NTP treatment caused the viability of host McCoy cells to diminish by 19%.
      Therefore, the results obtained demonstrated that (i) both extracellular and
      intracellular forms of C. trachomatis are sensitive to NTP treatment; (ii) the
      reduction in concentration of infectious bacteria after NTP treatment of infected
      cells is superior to the reduction in viability of host cells; and (iii) the
      effect of NTP on intracellular bacteria does not depend on UV rays.

PMID- 22361464
TI  - [Laparoscopic para-aortic lymphadenectomy in advanced cervical cancer: morbidity
      and impact on therapy].
AB  - BACKGROUND: Laparoscopic para-aortic lymphadenectomy (PAL) is being used
      increasingly to stage patients with locally advanced cervical cancer (LACC) and
      to define radiation field limits before chemoradiation therapy (CRT). This study
      aimed to define clinical implications, review complications, and determine
      whether surgical complications delayed the start of CRT. PATIENTS AND METHODS: We
      retrospectively reviewed a continuous series of patients with LACC, with no
      positive para-aortic (PA) nodes on positron emission tomography-computed
      tomography (PET-CT) and who had undergone a primary laparoscopic PAL. RESULTS:
      From November 2007 to June 2010, 98 patients with LACC underwent pretherapeutic
      PAL. Two patients did not undergo PAL: extensive carcinomatosis was discovered in
      one case and a technical problem arose in the other. No perioperative
      complications occurred. Seven patients had a lymphocyst requiring an imaging
      guided (or laparoscopic) puncture. Eight patients (8.4%, which corresponds to the
      false-negative PET-CT rate) had metastatic disease within PA lymph nodes. In
      cases of suspicious pelvic nodes on PET-CT, the risk for PA nodal disease was
      greater (24.0% versus 2.9%). When patients with and without surgical morbidity
      were compared, the median delay to the start of treatment was not significantly
      different (15 days; range, 3-49 days versus 18 days; range, 3-42 days).
      DISCUSSION AND CONCLUSIONS: The morbidity of laparoscopic PAL was limited and the
      completion of treatment was not delayed when complications occurred.
      Nevertheless, if PET-CT of the pelvic area is negative, the interest in staging
      PAL could be discussed because the risk for PA nodal disease is very low.

PMID- 22361463
TI  - Generation of Venus reporter knock-in mice revealed MAGI-2 expression patterns in
      adult mice.
AB  - The membrane-associated guanylate kinase inverted 2 (MAGI-2) protein, which is
      known to localize at the tight junction of epithelial cells, contains multiple
      copies of the PDZ and WW domains in its structure. Although the expression
      pattern of Magi2 mRNA in representative organs has been previously published, its
      detailed cellular distribution at the histological level remains unknown. Such
      detailed information would be useful to clarify the biological function of MAGI
      2. Here, we report the generation of Venus reporter knock-in mice for Magi2 in
      which exon 6 of the gene was substituted by the Venus-encoding sequence. We
      detected the expression of the Venus reporter protein in kidney podocytes from
      these knock-in mice. We also detected Venus reporter protein expression in
      spermatids within the testes and within neurons in various regions of the brain.
      Detection of the reporter protein from these diverse locations indicated the
      endogenous expression of MAGI-2 in these tissues. Our data suggested a potential
      function of MAGI-2 in the glomerular filtration process and sperm cell
      maturation. These data indicate that the Venus reporter knock-in mouse for Magi2
      is a useful model for the further study of Magi2 gene function. 

PMID- 22361465
TI  - [How I do... uterine artery Doppler velocimetry in first trimester of pregnancy].

PMID- 22361466
TI  - [Assessing ovarian cancer risk when considering elective oophorectomy at the time
      of hysterectomy--a challenge for the surgeon].

PMID- 22361467
TI  - [How I do... a 3D perineal ultrasonography].

PMID- 22361468
TI  - Hollow Ag@Pd core-shell nanotubes as highly active catalysts for the electro
      oxidation of formic acid.
AB  - Ag nanowires are prepared as templates by a polyol reduction process. Then Ag
      nanotubes coated with a thin layer of Pd are synthesized through sequential
      reduction accompanied with the galvanic displacement reaction. The products show
      a hollow core-shell nanotubular structure, as demonstrated by detailed
      characterizations. The Ag@Pd can significantly improve the electrocatalytic
      activity towards the electro-oxidation of formic acid and enhance the stability
      of the Pd component. It is proposed that the enhanced electrochemically active
      surface area and modulated electron structure of Pd by Ag are responsible for the
      improvement of electrocatalytic activity and durability. The results obtained in
      this work are different from those previous reports, in which alloy walls with
      hollow interiors are usually formed. This work provides a new and simple method
      for synthesizing novel bimetallic core-shell structure with a hollow interior,
      which can be applied as high-performance catalysts for the electro-oxidation of
      formic acid.

PMID- 22361469
TI  - Isolation and characterization of Pseudomonas brassicacearum J12 as an antagonist
      against Ralstonia solanacearum and identification of its antimicrobial
      components.
AB  - A bacterial strain, J12, isolated from the rhizosphere soil of tomato plants
      strongly inhibited the growth of phytopathogenic bacteria Ralstonia solanacearum.
      Strain J12 was identified as Pseudomonas brassicacearum based on its 16S rRNA
      gene sequence. J12 could produce 2,4-diacetylphloroglucinol (2,4-DAPG), hydrogen
      cyanide (HCN), siderophore(s) and protease. The maximum growth and antagonistic
      activity were recorded at 30 degrees C and pH 8. Glucose and tryptone were used
      as the most suitable carbon and nitrogen sources, respectively. Strain J12
      significantly suppressed tomato bacteria wilt by 45.5% in the greenhouse
      experiment. The main antimicrobial compound of J12 was identified as 2,4
      diacetylphloroglucinol (2,4-DAPG) by HPLC-ESI-MS analysis. The gene cluster
      phlACBD, which is responsible for 2,4-DAPG production, was identified and
      expressed in the bacterial strain Escherichia coli DH5alpha.

PMID- 22361470
TI  - Telomeres and longevity.

PMID- 22361471
TI  - Anti-human leukocyte antigen immunization after early allograft nephrectomy.
AB  - INTRODUCTION: The occurrence of de novo anti-human leukocyte antigen (HLA)
      antibodies and donor-specific antibodies (DSAs) after early graft loss is not
      well known. The aims of this single-center study were to evaluate the incidence
      of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for
      early graft loss and to seek the predictive factors for the development of DSAs.
      MATERIALS AND METHODS: Thirty-two patients, who experienced an early graft loss
      (<3 months after transplantation) and required an allograft nephrectomy, and who
      were considered for retransplantation, were included in the study. Anti-HLA
      antibodies were assessed, using the Luminex assay, before transplantation, on day
      15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6
      months until the last follow-up. RESULTS: The median time between transplantation
      and allograft nephrectomy was 2.5 (0-81) days. The median follow-up was 335 (30
      1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was
      56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in
      33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti
      HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors' epitopes.
      Induction therapy (type and dose) and the time between transplantation and
      allograft nephrectomy did not influence the incidence of DSAs. No independent
      predictive factor for the development of DSAs was identified. CONCLUSION: Even
      after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may
      develop in more than 50% of patients whose immunosuppression has been stopped
      after an allograft nephrectomy.

PMID- 22361472
TI  - Human leukocyte antigen-specific antibodies and gamma-interferon stimulate human
      microvascular and glomerular endothelial cells to produce complement factor C4.
AB  - BACKGROUND: The role of the complement system in antibody-mediated rejection has
      been investigated in relation to circulating complement interacting with renal
      microvascular endothelium, resulting in the formation of peritubular capillary
      C4d. However, the possible importance of local complement synthesis is less
      clear. The aim of this study was to determine whether human vascular endothelium
      could produce C4 in response to stimulation in vitro. METHODS: Human
      microvascular endothelial cells and glomerular endothelial cells were stimulated
      with endotoxins, cytokines, and human leukocyte antigen-specific antibodies.
      Synthesis of complement was investigated using western blotting and indirect
      immunofluorescence. De novo C4 synthesis was confirmed by using C4 small
      interfering RNA. RESULTS: Glomerular and microvascular endothelium, both produce
      C3 and C4 complement protein. Complement synthesis was stimulant-specific-C3 was
      produced mainly after stimulation with lipopolysaccharide whereas C4 synthesis
      occurred on treatment with gamma interferon. Culture with human leukocyte antigen
      specific antibodies resulted in a significant increase of C4 protein synthesis by
      both cell lines. CONCLUSIONS: We have shown for the first time that human
      microvascular endothelium can be stimulated to synthesize C4 in vitro. The
      implications of this for clinical transplantation, especially in the context of
      antibody-mediated rejection, its histological interpretation and as a potential
      target for therapy would have to be determined by further studies.

PMID- 22361473
TI  - Large and giant ventral paraclinoid carotid aneurysms: surgical techniques,
      complications and outcomes.
AB  - OBJECTIVES: Surgical treatment of large and giant ventral paraclinoid carotid
      aneurysms (vPCAs) continues to be challenging and technically demanding for
      vascular neurosurgeons. Due to both physiological barriers and limitations of
      current surgical technology in the treatment of vPCAs, higher rates of morbidity
      and mortality are a given. To improve the current available data and assess the
      most effective microsurgical management techniques with the goal of decreased
      morbidity and mortality, we present this retrospective study of a series of 15
      consecutive patients with large and giant vPCAs. MATERIALS AND METHODS: Between
      January 2005 and December 2010, fifteen patients presented with large or giant
      vPCAs were surgically treated at West China Hospital and were included in this
      study. The data was retrospectively analyzed. RESULTS: Five men and ten women
      with an averaging 50 years of age (ranged 32-70 years) were included in this
      study. The average aneurysm size was 21 mm (ranged 13-36 mm). All patients were
      treated microsurgically. Twelve patients (80%) had desirable surgical outcomes
      (Glasgow Outcome Score 4-5) at follow-up for a mean of 32 months (range 3-72
      months). One patient (7%) died of severe vasospasm after surgery. The surgical
      mortality was 7%; overall morbidity was 27%, including the hemiplegia, oculomotor
      paresis and visual deficit. None of the 14 following patients had rebleeding or
      regrowth of residual aneurysm during this follow-up period. Age and Hunt-Hess
      grade were significantly correlated with clinical outcome. CONCLUSIONS: Despite
      the difficulties presented by large and giant vPCAs, our increased knowledge of
      anatomy and refinements in operative techniques and intraoperative monitoring
      have greatly improved the clinical outcome with a more acceptable mortality and
      morbidity.

PMID- 22361474
TI  - The epidemiology of sports-related injuries in older adults: a central European
      epidemiologic study.
AB  - BACKGROUND AND AIMS: The population is rapidly aging and remaining more active
      over the age of 65. An increasing number of sports related injuries in
      individuals 65 and older are thus anticipated. The aim of this study is to
      analyze the epidemiology of sports injuries in the age group aged 65 and older.
      METHODS: Data from the medical records of adults aged 65 years and older who were
      treated for sports-related injuries at a level one trauma center between December
      1994 and February 2008 was collected and statistically analyzed. RESULTS: A total
      of 2635 patients met our inclusion criteria. There were 1647 men (62.5%) and 988
      women (37.5%) with a mean age of 70.9 years. The yearly number of injuries
      doubled during the study period (1996-2007). The most common mechanism of injury
      was a simple fall from standing height (69%). Nearly 75% of all injuries occurred
      during alpine skiing, cycling or mountain climbing. The median Injury Severity
      Score was 4. Minor injuries and wounds (40%) were recorded most commonly followed
      by fractures (27%), sprains, ligament injuries (19%) and injuries of muscles and
      tendons (6%). The most frequent diagnoses were minor injuries to the head and
      ligament injuries around the knee joint. Injuries to the upper extremities
      occurred in 33.7%, injuries to the lower extremities in 29.4% and injuries to the
      head occurred in 20% of the patients. Women sustained substantially more
      fractures than men. CONCLUSION: Adults aged 65 and older are remaining active in
      sports, which results in higher numbers of sports related injuries in this age
      group. Identification of type, mechanism and distribution of the injuries can
      help with the recognition of risk factors for injury. This may enable us to
      develop appropriate preventative measures to reduce the incidence, and morbidity
      of such injuries.

PMID- 22361475
TI  - The Enamovirus P0 protein is a silencing suppressor which inhibits local and
      systemic RNA silencing through AGO1 degradation.
AB  - The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the
      plant's RNA silencing machinery. Here we identified a silencing suppressor
      protein (SSP), P0(PE), in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and
      showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal
      yellow dwarf virus have strong local and systemic SSP activity, while the P1 of
      Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear
      localized P0(PE) has no discernable sequence conservation with known SSPs, but
      proved to be a strong suppressor of local silencing and a moderate suppressor of
      systemic silencing. Like the P0s from poleroviruses, P0(PE) destabilizes AGO1 and
      this action is mediated by an F-box-like domain. Therefore, despite the lack of
      any sequence similarity, the poleroviral and enamoviral SSPs have a conserved
      mode of action upon the RNA silencing machinery.

PMID- 22361476
TI  - Internal polyadenylation of parvoviral precursor mRNA limits progeny virus
      production.
AB  - Aleutian Mink Disease Virus (AMDV) is the only virus in the genus Amdovirus of
      family Parvoviridae. In adult mink, AMDV causes a persistent infection associated
      with severe dysfunction of the immune system. Cleavage of AMDV capsid proteins
      has been previously shown to play a role in regulating progeny virus production
      (Fang Cheng et al., J. Virol. 84:2687-2696, 2010). The present study shows that
      AMDV has evolved a second strategy to limit expression of capsid proteins by
      preventing processing of the full-length capsid protein-encoding mRNA
      transcripts. Characterization of the cis-elements of the proximal polyadenylation
      site [(pA)p] in the infectious clone of AMDV revealed that polyadenylation at the
      (pA)p site is controlled by an upstream element (USE) of 200 nts in length, the
      AAUAAA signal, and a downstream element (DSE) of 40 nts. A decrease in
      polyadenylation at the (pA)p site, either by mutating the AAUAAA signal or the
      DSE, which does not affect the encoding of amino acids in the infectious clone,
      increased the expression of capsid protein VP1/VP2 and thereby increased progeny
      virus production approximately 2-3-fold. This increase was accompanied by
      enhanced replication of the AMDV genome. Thus, this study reveals correlations
      among internal polyadenylation, capsid production, viral DNA replication and
      progeny virus production of AMDV, indicating that internal polyadenylation is a
      limiting step for parvovirus replication and progeny virus production.

PMID- 22361477
TI  - A two-hit model: behavioural investigation of the effect of combined neonatal MK
      801 administration and isolation rearing in the rat.
AB  - This study combined two neurodevelopmental manipulations, neonatal MK-801
      treatment and isolation rearing, to produce a 'two-hit' model and determine
      whether two hits induce a more robust behavioural phenotype of an animal model of
      aspects of schizophrenia compared with individual manipulations alone. The effect
      of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK
      801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10
      and were assigned to group or isolation rearing at weaning (PND 21). From PND 77,
      they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were
      subjected to three prepulse inhibition (PPI) tests, a locomotor activity
      assessment and a novel object recognition task. MK-801-treated rats reared in
      isolation displayed robust PPI disruptions which were consistently manifested in
      all three tests. PPI deficits were also detected in saline-treated rats reared in
      isolation but not in all tests. Only the two-hit rats demonstrated
      hyperlocomotion and impaired object recognition memory. Clozapine restored PPI
      anomalies in the two-hit rats. The two-hit model showed greater psychotic-like
      effects than either neonatal MK-801 or isolation rearing alone. The preliminary
      predictive validity shown with clozapine suggests this model may be useful for
      predicting the efficacy of putative antipsychotics.

PMID- 22361478
TI  - Bladder pain syndrome associated with highest impact on sexual function among
      women with lower urinary tract symptoms.
AB  - OBJECTIVE: To investigate the differential impact of lower urinary tract symptoms
      (LUTS) on female sexual function (FSF). METHODS: In a cross-sectional study in
      Agostino Gemelli Hospital, Rome, Italy, 188 sexually active patients with LUTS,
      as assessed by self-reported questionnaires, underwent comprehensive urologic and
      urodynamic examination between January 2008 and December 2010. Patients with
      urinary incontinence, voiding-phase LUTS, overactive bladder (OAB), and bladder
      pain syndrome (BPS) were included. FSF was assessed by PISQ-12 questionnaire, and
      scores (0-100; higher scores indicate worse FSF) were compared between the
      patients and a group of age-matched women without LUTS. PISQ-12 scores of
      different clinical and urodynamic patient subgroups were also compared by
      multivariate analysis. RESULTS: The global PISQ-12 mean score was significantly
      higher among patients with LUTS (32.7) than among controls (18.4; P<0.0001).
      Women with BPS reported the highest global PISQ-12 score (46.1), followed by
      those with urodynamic detrusor overactivity (45.0), clinical urgency (41.4),
      mixed (37.7) and stress urinary incontinence (28.1), dry OAB (22.2) and voiding
      phase LUTS (19.6). Age, urinary incontinence, BPS, and detrusor overactivity were
      independent predictors of FSF. CONCLUSION: BPS was associated with the greatest
      impairment of FSF among women with LUTS. Clinical and urodynamic urgency-type
      urinary incontinence affected FSF more markedly than other types.

PMID- 22361479
TI  - Acquired lymphangioma circumscriptum of the vulva.

PMID- 22361480
TI  - Predictive factors for failure of pelvic arterial embolization for postpartum
      hemorrhage.
AB  - OBJECTIVE: To assess the efficacy of pelvic embolization in women with postpartum
      hemorrhage (PPH) and to determine factors associated with embolization failure.
      METHODS: In a retrospective observational study, data were analyzed from 98
      consecutive women who underwent pelvic embolization for intractable PPH between
      January 2007 and November 2009 at Beaujon Hospital, Clichy, France. Women with
      persistent PPH despite pelvic embolization were compared with women who had
      cessation of hemorrhage and attained hemodynamic stability. RESULTS: Among the 98
      women, 66 (67.3%) had been transferred from another hospital after delivery.
      Pelvic arterial embolization failed to control PPH in 8 (8.2%) women. On
      univariate analysis, factors significantly associated with embolization failure
      were the presence of placenta accreta (P<0.005), hemoglobin level (P<0.05),
      prothrombin time (P<0.04), fibrinogen level (P<0.03), red blood transfusion
      (P<0.02), number of packed red blood cell units transfused (P<0.05), and fresh
      frozen plasma transfusion (P<0.02). Hospital-to-hospital transfer with a notable
      time interval between delivery and embolization was not associated with increased
      risk of failure. CONCLUSION: Predictive factors significantly associated with
      failed pelvic arterial embolization were the presence of placenta accreta,
      biologic factors, and transfusional factors. Delay due to inter-hospital transfer
      did not affect the outcome of embolization.

PMID- 22361482
TI  - Perioperative management of pheochromocytoma: focus on magnesium, clevidipine,
      and vasopressin.
AB  - The perioperative management of pheochromocytomas requires meticulous anesthetic
      care. There has been considerable progress in its management, recently 3 agents
      that may be particularly advantageous to the anesthetic team have been
      identified. Magnesium sulfate is readily available, cheap, safe, and effective
      for hemodynamic control before tumor resection. It has demonstrated efficacy in
      adults, children, and in rarer scenarios, such as pheochromocytoma resection in
      pregnancy and in pheochromocytoma crises. Although only recently entering
      clinical practice, clevidipine exhibits a pharmacologic profile of great
      interest, showing efficacy in the management of hypertensive crisis and providing
      rapid titration and precise hemodynamic control. Its application in the
      perioperative management of pheochromocytoma before tumor resection recently has
      been described and likely will expand in the near future. Vasopressin has
      demonstrated utility in the management of catecholamine-resistant shock after
      tumor resection. A familiarity with these 3 agents offers anesthesia providers
      further effective pharmacologic options for managing the hemodynamic challenges
      inherent to this population before and after tumor resection.

PMID- 22361483
TI  - Role of ketamine in the management of pulmonary hypertension and right
      ventricular failure.

PMID- 22361484
TI  - Ultrasound-guided cannulation of radial artery with anatomic variation.

PMID- 22361486
TI  - The effects of gabapentin on acute and chronic postoperative pain after coronary
      artery bypass graft surgery.

PMID- 22361488
TI  - Video laryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube
      intubation: a retrospective analysis.
AB  - OBJECTIVE: The authors hypothesized that video laryngoscopy (VL) facilitated
      double-lumen tube (DLT) insertion compared with direct laryngoscopy (DL). DESIGN:
      A retrospective analysis. SETTING: An academic hospital. PARTICIPANTS: Patients
      older than 18 years of age undergoing thoracic surgery requiring DLT placement
      between 2005 and 2011. INTERVENTIONS: Patients without airway predictors of
      difficult intubation who were intubated under DL with Macintosh (DL-MAC, n = 40)
      or Miller (DL-MIL, n = 44) blades and VL with McGrath MAC (Aircraft Medical,
      Edinburgh, UK) and C-MAC (Karl Storz, Tuttlingen, Germany) laryngoscopes (n = 46)
      were included in the study. Patients who were intubated with both VL devices were
      grouped into a VL group. MEASUREMENTS: Patients in all 3 groups had comparable
      preoperative demographics. Mallampati scores and ease of manual ventilation after
      the induction of anesthesia were also similar in all groups. The Cormack Lehane
      (C-L) grade views were significantly higher in patients in the DL-MAC than in the
      DL-MIL and VL groups (p < 0.006). The number of intubation attempts was similar
      in all 3 groups; however, the percentage of intubation reported to be difficult
      was higher in the DL-MAC than in the other 2 groups (p = 0.014). No damage to the
      airway was found in any of the groups. CONCLUSION: DLT placement using VL
      appeared to overcome some of the limitations of DL-MAC but was similar to DL-MIL.
      The authors speculated that the ease of placement was related to the improved
      visualization of the vocal cords because there was a significantly greater number
      of C-L views 3 and 4 in the DL-MAC group as compared with the VL and DL-MIL
      groups. Hence, the authors advocate using VL, particularly when the
      laryngoscopist is inexperienced using DL-MIL for DLT placement.

PMID- 22361487
TI  - An unusual "swinging" biatrial mass.

PMID- 22361489
TI  - Miltefosine triggers a strong proinflammatory cytokine response during visceral
      leishmaniasis: role of TLR4 and TLR9.
AB  - Visceral leishmaniasis (VL) caused by the protozoan parasite, Leishmania
      donovani, is associated with irregular fever, weight loss, hepatosplenomegaly and
      anemia. The therapeutic arsenal against VL is limited and the recent advent of a
      novel immunomodulatory drug, Miltefosine has shown promising results for
      effective treatment of VL but its dependence on Toll like receptors (TLR) has not
      been explored. In this study, we have shown that the non-cytotoxic dose (5 MUM)
      of Miltefosine could render significant protection corresponding to 88% and 95%
      reduction in intracellular parasite load at 24 h and 48 h in L. donovani infected
      THP1 cells. This was accompanied by a strong proinflammatory cytokine response in
      the form of IFN-gamma, IL-12 and TNF-alpha as evident by enzyme linked
      immunosorbent assay (ELISA) and real time PCR (RT-PCR). This Miltefosine induced
      proinflammatory cytokine response in infected THP1 cells was also accompanied by
      simultaneous 10- and 12-fold increase in TLR4 mRNA and TLR9 mRNA. These changes
      in cytokine response and TLR expression were also studied in peripheral blood
      mononuclear cells (PBMC) of VL patients treated with Miltefosine by RT-PCR which
      showed similar results as in THP1 cells. Thereby, suggesting a probable
      dependence of Miltefosine on TLR4 and TLR9 in triggering a proinflammatory
      response.

PMID- 22361490
TI  - High capacity, reversible alloying reactions in SnSb/C nanocomposites for Na-ion
      battery applications.
AB  - A new SnSb/C nanocomposite based on Na alloying reactions is demonstrated as
      anode for Na-ion battery applications. The electrode can achieve an exceptionally
      high capacity (544 mA h g(-1), almost double that of intercalation carbon
      materials), good rate capacity and cyclability (80% capacity retention over 50
      cycles) for Na-ion storage.

PMID- 22361491
TI  - Sonochemical degradation of cyclic nitroxides in aqueous solution.
AB  - The sonochemical degradation of eight five- and six-membered nitroxides has been
      studied by EPR spectroscopy after exposure to ultrasound at a frequency of 354
      kHz in argon-saturated aqueous solution. Concentration vs. time profiles do not
      follow a simple rate law. Octanol/water partition functions have been determined
      for all eight nitroxides, and an excellent linear correlation has been found
      between initial decomposition rates and hydrophobicity (log K(octanol/water)).
      Variation of initial rate with concentration was investigated for one compound
      (TEMPONE) and is largely consistent with an equilibrium distribution of substrate
      between bulk solution and the gas/liquid interface.

PMID- 22361492
TI  - Correlation between the magnetic imaging of cobalt nanoconstrictions and their
      magnetoresistance response.
AB  - Scanning transmission x-ray microscopy (STXM) and magnetoresistance (MR)
      measurements are used to investigate the magnetic behavior of a nanoconstriction
      joining two micrometric electrodes (a pad and a wire). The reversal of the
      magnetization under variable external static magnetic fields is imaged. By means
      of a detailed analysis of the STXM images at the nanocontact area, the MR is
      calculated, based on diffusive anisotropic-MR. This MR agrees well with that
      obtained from electrical transport measurements, allowing a direct correlation
      between the MR signal and the magnetic reversal of the system. The magnetization
      behavior depends on the sample thickness and constriction dimensions. In 40 nm
      thick samples, with 20 * 175 nm(2) contact areas, the magnetization at the two
      sides of the constriction forms a net angle of 90 degrees , with a progressive
      evolution of the magnetization structure between the electrodes during switching.
      The MR in those cases has a more peaked shape than with 20 nm-thick electrodes
      and 10 * 80 nm(2) contact areas, where the magnetization forms 180 degrees 
      between them, with a wide domain wall pinned at the constriction. As a
      consequence of this configuration, a plateau in the MR is observed for about 20
      Oe.

PMID- 22361493
TI  - Tumors of the body and tail of the pancreas.
AB  - THE ABSTRACT IS AVAILABLE AT THE CLINICAL PANCREATIC DISORDER I: Acute
      pancreatitis. North Am J Med Sci 2011; 3: 316-319. doi: 10.4297/najms.2011.3316.

PMID- 22361494
TI  - Triterpenoids from the spores of Ganoderma lucidum.
AB  - Recently a series of triterpenoids were isolated from ganoderma spores and have
      drawn the attention of chemists and pharmacists. The aim of this review is to
      summarize the triterpenoids and their bioactivities of ganoderma spores. The
      chemical and biological literatures of ganoderma spores dealing with the
      structural analysis and bioactivity assay were selected. Triterpenoids isolated
      from ganoderma spores showed significantly anti-HIV-1 protease, anti-tumor, and
      anti-complement activities. Triterpenoids are the main active constituents of
      ganoderma spores and show various bioactivities for its medicinal use. In
      addition, biological activities of ganoderma spores still need further assessment
      before they can be accepted not only by the traditional Asian medicine community,
      but also by western science and medicine.

PMID- 22361495
TI  - Management of common adverse effects in the era of highly active antiretroviral
      therapy in south east Ethiopia.
AB  - BACKGROUND: The combination of antiretroviral therapy is the corner stone of
      management of patients with human immune deficiency virus infection. Although
      antiretroviral therapy can reduce viral load to undetectable level, improve the
      immunity and prolong survival of patients, antiretroviral drugs are associated
      with many adverse effects that may be severe and affect patient adherence and
      quality of life. AIMS: The aim of this study was to assess management strategies
      under taken in patient's experienced common adverse effects of highly active
      antiretroviral therapy in Goba Hospital antiretroviral clinic. PATIENTS AND
      METHODS: A cross sectional study of patient record chart of patients who had
      follow-up during data collection period was done followed by patient interview.
      Data was filled on well structured questionnaire and analyzed using SPSS for
      window version 16.0. RESULTS: The common adverse effects were Rash (48.8%),
      Peripheral neuropathy (36.9%) and Anemia (20.24%). The rate of management was
      39.3%. Pyridoxine (36.8%) was commonly prescribed drug for management of
      Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs
      for management of Rash and Anemia respectively. Use of traditional healers
      (57.7%) was leading reason for non-management. CONCLUSION: Rate of management for
      common adverse effect is low. Education should be given on adverse effects for
      patients.

PMID- 22361496
TI  - Modulation of immune tolerance with a Chinese traditional prescription inhibits
      allergic rhinitis in mice.
AB  - BACKGROUND: Allergic diseases substantially affect human health and social
      economy. The pathogenesis is to be further understood. The effect of current
      therapeutic remedies on allergic diseases is not satisfactory. AIMS: This study
      aimed to inhibit allergic rhinitis in a mouse model with a Chinese traditional
      medical prescription, Bu-Zhong-Yi-Qi-Tang. MATERIAL AND METHODS: A mouse AR model
      was developed with ovalbumin (OVA) plus adjuvant alum. The AR clinical symptoms
      and immune pathology in the nasal mucosa were assessed with the AR mouse model.
      Some mice were treated with Bu-Zhong-Yi-Qi-Tang via gavage-fed. The immune
      tolerance status in the nasal mucosa was evaluated by counting the numbers of
      tolerogenic dendritic cells (DC) and regulatory T cells (Treg). RESULTS: After
      exposure to the specific antigen, OVA, the sensitized mice had AR-like symptoms
      including nasal itch and sneeze. The frequency of mast cells, levels of IgE/IL-4
      in nasal mucosa was markedly higher in sensitized mice than naive controls; while
      the levels of integration alphavbeta6 (avb6), the number of tolerogenic DCs and
      Tregs in nasal mucosa were significantly lower than naive control mice. The AR
      like symptoms and immune pathology and immune tolerance status in the AR nasal
      mucosa were substantially improved by administration with Bu-Zhong-Yi-Qi-Tang.
      CONCLUSIONS: The immune tolerance status is impaired in the AR nasal mucosa that
      can be improved by administering with Bu-Zhong-Yi-Qi-Tang.

PMID- 22361497
TI  - Percutaneous dilatational versus conventional surgical tracheostomy in intensive
      care patients.
AB  - BACKGROUND: Tracheostomy is usually performed in patients with difficult weaning
      from mechanical ventilation or some catastrophic neurologic insult. Conventional
      tracheostomy involves dissection of the pretracheal tissues and insertion of the
      tracheostomy tube into the trachea under direct vision. Percutaneous dilatational
      tracheostomy is increasingly popular and has gained widespread acceptance in many
      intensive care unit and trauma centers. AIM: Aim of the study was to compare
      percutaneous dilatational tracheostomy versus conventional tracheostomy in
      intensive care patients. PATIENTS AND METHODS: 64 critically ill patients
      admitted to intensive care unit subjected to tracheostomy and randomly divided
      into two groups; percutaneous dilatational tracheostomy and conventional
      tracheostomy. RESULTS: Mean duration of the procedure was similar between the two
      procedures while the mean size of tracheostomy tube was smaller in percutaneous
      technique. In addition, the Lowest SpO(2) during procedure, PaCO(2) after
      operation and intra-operative bleeding for both groups were nearly similar
      without any statistically difference. Postoperative infection after 7 days seen
      to be statistically lowered and the length of scar tend to be smaller among PDT
      patients. CONCLUSION: PDT technique is effective and safe as CST with low
      incidence of post operative complication.

PMID- 22361499
TI  - An unusual case of altered mental status in a young woman.
AB  - CONTEXT: We describe a case of paraneoplastic neurologic syndrome, namely N
      Methyl-D-Aspartic acid receptor antibody associated limbic encephalitis, a rare
      cause of altered mental status in the young. CASE REPORT: A 28 year old Caucasian
      female nurse presented with acute onset difficulty with word finding and
      increasing confusion and agitation. She also had visual hallucinations, transient
      episodes of unresponsiveness, and lingual dyskinesias. Workup including blood,
      imaging and regular cerebrospinal fluid (CSF) studies was unremarkable. She
      subsequently developed complex partial seizures. Computerized Tomography scan of
      chest/abdomen/pelvis revealed a dermoid cyst of the left ovary and CSF N-Methyl-D
      Aspartic acid receptor antibody returned positive confirming the diagnosis of
      paraneoplastic NMDA receptor antibody associated limbic encephalitis. She was
      treated with methylprednisolone therapy along with plasmapheresis and a left
      salpingo-opherectomy was performed. The patient showed significant improvement
      with respect to her cognitive function and had no more seizures. CONCLUSION: N
      Methyl-D-Aspartic acid receptor antibody associated limbic encephalitis is a rare
      paraneoplastic neurologic syndrome with symptoms including psychiatric
      manifestations, seizures, language disturbances and autonomic instability. It
      develops due to antibody induced decrease in N-Methyl-D-Aspartic acid receptors.
      There is a significant association with ovarian teratoma in >50% female cases.
      Treatment includes resection of tumor, glucocorticoids, plasmapheresis and
      Intravenous Immunoglobulin therapy.

PMID- 22361498
TI  - Experimental evaluation of anti-inflammatory effect of topical application of
      entada phaseoloides seeds as paste and ointment.
AB  - AIMS: The study was to study the anti-inflammatory effect of topical application
      of different formulations of seed pulp of entada phaseoloides. METHOD AND
      MATERIAL: After removing the shell, entada phaseoloides seeds were powdered.
      Paste was prepared with water and ointment with polyethylene glycol & Carbowax
      3350. 32 Wister rats of either sex weighing 140-200 gram were divided into four
      groups, Group-I vehicle, Group-II entada phaseoloides paste, Group-III entada
      phaseoloides Ointment, Group-IV Diclofenac sodium Ointment. Arthritis was induced
      by injecting 0.1ml Complete Freund's adjuvant in sub plantar region of the left
      hind paw. Drug treatment was started on the same day and given for 12 days. Paw
      volume was measured with Plethysmometer on day 0, 1, 5, 12 and 21 for both the
      paws. Bodyweight and Gait was observed throughout the study. RESULTS: Localized
      inflammatory reaction developed in all the rats in 24 hours. In control group,
      there was no resolution of swelling even in 21 days. Both EP formulations showed
      significant (P < 0.001) anti-inflammatory activity as compared to control. entada
      phaseoloides ointment was equi-effective to that of Diclofenac sodium on 12(th)
      day. entada phaseoloides paste was significantly (P < 0.05) more effective than
      Diclofenac sodium on 21(st) day. CONCLUSION: Both the formulations of entada
      phaseoloides have anti-inflammatory activity and entada phaseoloides paste is
      significantly more effective than diclofenac sodium.

PMID- 22361500
TI  - Autoimmune pancreatitis mimicking pancreatic cancer.
AB  - CONTEXT: Autoimmune pancreatitis is a particular type of pancreatitis of presumed
      autoimmune etiology, it is an entity distinct from all others forms of chronic
      pancreatitis, characterized by clinical, histopathological, radiographic,
      serologic and therapeutic features. This benign disease resembles pancreatic
      carcinoma both clinically and radiographically. CASE REPORT: A 27-year-old man
      presented with obstructive jaundice and evocative image of pancreatic tumor. A
      pancreaticoduodenectomy (Whipple operation) was performed and pathological
      examination of the specimen diagnosed AIP. Patient responded well to a course of
      corticosteroids with resolution of clinical and biological disorders. CONCLUSION:
      Accurate and timely diagnosis of autoimmune pancreatitis is particularly
      important because steroid therapy is effective and pancreatic resection is not
      necessary.

PMID- 22361501
TI  - Enoxaparin-associated giant retroperitoneal hematoma in pulmonary embolism
      treatment.
AB  - CONTEXT: Retroperitoneal hematoma may usually occur as a result of trauma. A life
      threatening retroperitoneal hematoma is not expected complication of
      anticoagulation treatment and rarely reported. Low molecular weight heparins
      (Enoxaparin) which are used as effective and safe medicine in the venous
      thromboemboly treatment have some major complications such as hematomas of
      different organs. We aim to present a giant spontaneous retroperitoneal hematoma
      after anticoagulant treatment of pulmonary embolism with enoxaparin. CASE REPORT:
      A 73-year-old male patient with the diagnosis of pulmonary embolism underwent
      anticoagulant treatment (enoxaparin). In the second day of admission, the patient
      had an episode of abdominal and back pain. Abdominal ultrasonography and
      computerized tomographic scan revealed a giant retroperitoneal hematoma.
      Enoxaparin treatment was then stopped and the supportive treatment was started.
      In the following days, hemoglobin levels returned to normal and a control CT
      revealed regression of hematoma size. CONCLUSION: The anticoagulant treatment
      with enoxaparin may lead to severe hematomas. Therefore, the clinical suspicion
      is required especially in elderly patients and patients with impaired renal
      function for retroperitoneal hematoma, when they suffer from acute abdominal
      pain.

PMID- 22361502
TI  - Secondary gliosarcoma after the treatment of primary glioblastoma multiforme.
AB  - CONTEXT: Gliosarcoma is a rare variant of glioblastoma multiforme containing
      distinct gliomatous and sarcomatous components. Gliosarcoma comprise 1.8-8% of
      glioblastoma multiforme and are clinically similar to them, affecting adults in
      the fourth and sixth decades of life, with a higher proportion found in males.
      The survival for patients with Gliosarcoma is equally poor as for those with
      glioblastoma multiforme, and there is a greater propensity for extracranial
      metastasis in Gliosarcoma. Clinical treatment-related experience reported in the
      literature is limited, and Gliosarcoma are currently treated in a similar fashion
      to glioblastoma multiforme, with modalities including tumor resection,
      postoperative radiation therapy, and chemotherapy. Gliosarcoma can arise
      secondarily, after conventional adjuvant treatment of high-grade glioma. The
      current literature on the occurrence of secondary gliosarcoma after glioblastoma
      multiforme is limited, with only 54 reported cases. CASE REPORT: The authors
      present a 48-year-old Caucasian male who had previously received postoperative
      combined radiation and temozolomide chemotherapy for glioblastoma multiforme.
      After a free disease period of 9 months the disease recurs as Gliosarcoma. The
      patient underwent a Total surgical excision and received chemotherapy with a
      basis of bevacizumab and irinotecan. The patient died from tumor progression 5
      months after gliosarcoma diagnosis. CONCLUSION: The poor survival of patients
      with secondary gliosarcoma who had previously received combined radiation and
      temozolomide chemotherapy for glioblastoma multiforme may reflect a unique
      molecular profile of glioblastoma multiforme that eventually recurs as secondary
      gliosarcoma. We have to keep in mind the possibility of gliosarcomatous change in
      the recurrence of malignant glioma. Awareness of this pathological entity will
      allow more rapid diagnosis and treatment.

PMID- 22361503
TI  - Patients' experience of asthma control and clinical guidelines: perspectives from
      a qualitative study.
AB  - BACKGROUND: Clinical guidelines consider the concept of 'asthma control' as the
      primary goal of asthma treatment. This study aimed to explore patients' views of
      concepts that are important for understanding and evaluating asthma control.
      METHODS: Patients with mild to severe asthma in four countries completed the
      Asthma Control Questionnaire (ACQ) and discussed their experiences in focus
      groups. Clinicians evaluated patients' levels of asthma control based on Global
      Initiative for Asthma (GINA) guidelines. Clinician- and questionnaire-based
      ratings of asthma control were compared. Thematic analysis was used to identify
      key concepts from focus group transcripts. RESULTS: The sample consisted of 55
      patients. Classification of asthma control, based on the ACQ, was consistent with
      clinician rating in 28 cases (51%). In focus groups, patients discussed concepts
      related to symptoms, asthma attacks (exacerbations), activity limitations,
      panic/fear, tiredness, sleep disturbances (nocturnal awakening and difficulty
      falling asleep), and rescue medication use when describing asthma control.
      Clinical guidelines also focus on symptoms, activity limitations, rescue
      medication use, and exacerbations but, in addition include lung function
      parameters. Guidelines do not take into account asthma-related panic/fear or
      tiredness and sleep disturbances beyond nocturnal awakening. CONCLUSION: The
      results of this study suggest that patients' understanding of asthma control
      extends beyond the usual clinical manifestation of respiratory symptoms and lung
      function. This may have implications for clinical practice, for setting and
      achieving the goals of asthma control as well as for evaluation of treatments for
      asthma from the patients' perspective.

PMID- 22361504
TI  - Variation in enamel thickness within the genus Homo.
AB  - Recent humans and their fossil relatives are classified as having thick molar
      enamel, one of very few dental traits that distinguish hominins from living
      African apes. However, little is known about enamel thickness in the earliest
      members of the genus Homo, and recent studies of later Homo report considerable
      intra- and inter-specific variation. In order to assess taxonomic, geographic,
      and temporal trends in enamel thickness, we applied micro-computed tomographic
      imaging to 150 fossil Homo teeth spanning two million years. Early Homo
      postcanine teeth from Africa and Asia show highly variable average and relative
      enamel thickness (AET and RET) values. Three molars from South Africa exceed Homo
      AET and RET ranges, resembling the hyper thick Paranthropus condition. Most later
      Homo groups (archaic European and north African Homo, and fossil and recent Homo
      sapiens) possess absolutely and relatively thick enamel across the entire
      dentition. In contrast, Neanderthals show relatively thin enamel in their
      incisors, canines, premolars, and molars, although incisor AET values are similar
      to H. sapiens. Comparisons of recent and fossil H. sapiens reveal that dental
      size reduction has led to a disproportionate decrease in coronal dentine compared
      with enamel (although both are reduced), leading to relatively thicker enamel in
      recent humans. General characterizations of hominins as having 'thick enamel'
      thus oversimplify a surprisingly variable craniodental trait with limited
      taxonomic utility within a genus. Moreover, estimates of dental attrition rates
      employed in paleodemographic reconstruction may be biased when this variation is
      not considered. Additional research is necessary to reconstruct hominin dietary
      ecology since thick enamel is not a prerequisite for hard-object feeding, and it
      is present in most later Homo species despite advances in technology and food
      processing.

PMID- 22361505
TI  - New understandings on folliculogenesis/oogenesis regulation in mouse as revealed
      by conditional knockout.
AB  - In comparison to conventional knockout technology and in vitro research methods,
      conditional gene knockout has remarkable advantages. In the past decade,
      especially during the past five years, conditional knockout approaches have been
      used to study the regulation of folliculogenesis, follicle growth, oocyte
      maturation and other major reproductive events. In this review, we summarize the
      recent findings about folliculogenesis/oogenesis regulation, including the
      functions of four signaling cascades or glycoprotein domains that have been
      extensively studied by conditional gene deletion. Several other still fragmented
      areas of related work are introduced which are awaiting clarification. We have
      also discussed the future potential of this technology in clarifying gene
      functions in reproductive biology.

PMID- 22361507
TI  - Arabidopsis AtVPS15 plays essential roles in pollen germination possibly by
      interacting with AtVPS34.
AB  - VPS15 protein is a component of the phosphatidylinositol 3-kinase complex which
      plays a pivotal role in the development of yeast and mammalian cells. The
      knowledge about the function of its homologue in plants remains limited. Here we
      report that AtVPS15, a homologue of yeast VPS15p in Arabidopsis, plays an
      essential role in pollen germination. Homozygous T-DNA insertion mutants of
      AtVPS15 could not be obtained from the progenies of self-pollinated heterozygous
      mutants. Reciprocal crosses between atvps15 mutants and wild-type Arabidopsis
      revealed that the T-DNA insertion was not able to be transmitted by male
      gametophytes. DAPI staining, Alexander's stain and scanning electron microscopic
      analysis showed that atvps15 heterozygous plants produced pollen grains that were
      morphologically indistinguishable from wild-type pollen, whereas in vitro
      germination experiments revealed that germination of the pollen grains was
      defective. GUS staining analysis of transgenic plants expressing the GUS reporter
      gene driven by the AtVPS15 promoter showed that AtVPS15 was mainly expressed in
      pollen grains. Finally, DUALmembrane yeast two-hybrid analysis demonstrated that
      AtVPS15 might interact directly with AtVPS34. These results suggest that AtVPS15
      is very important for pollen germination, possibly through modulation of the
      activity of PI3-kinase.

PMID- 22361506
TI  - Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere
      organization in zebrafish embryonic slow muscles.
AB  - Myofibrillogenesis, the process of sarcomere formation, requires close
      interactions of sarcomeric proteins and various components of sarcomere
      structures. The myosin thick filaments and M-lines are two key components of the
      sarcomere. It has been suggested that myomesin proteins of M-lines interact with
      myosin and titin proteins and keep the thick and titin filaments in order.
      However, the function of myomesin in myofibrillogenesis and sarcomere
      organization remained largely enigmatic. No knockout or knockdown animal models
      have been reported to elucidate the role of myomesin in sarcomere organization in
      vivo. In this study, by using the gene-specific knockdown approach in zebrafish
      embryos, we carried out a loss-of-function analysis of myomesin-3 and slow myosin
      heavy chain 1 (smyhc1) expressed specifically in slow muscles. We demonstrated
      that knockdown of smyhc1 abolished the sarcomeric localization of myomesin-3 in
      slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric
      organization of thick and thin filaments as well as M- and Z-line structures.
      Together, these studies indicate that myosin thick filaments are required for M
      line organization and M-line localization of myomesin-3. In contrast, myomesin-3
      is dispensable for sarcomere organization in slow muscles.

PMID- 22361508
TI  - Identification of a ubiquitin-binding structure in the S-locus F-box protein
      controlling S-RNase-based self-incompatibility.
AB  - In flowering plants, self-incompatibility (SI) serves as an important
      intraspecific reproductive barrier to promote outbreeding. In species from the
      Solanaceae, Plantaginaceae and Rosaceae, S-RNase and SLF (S-locus F-box) proteins
      have been shown to control the female and male specificity of SI, respectively.
      However, little is known about structure features of the SLF protein apart from
      its conserved F-box domain. Here we show that the SLF C-terminal region possesses
      a novel ubiquitin-binding domain (UBD) structure conserved among the SLF protein
      family. By using an ex vivo system of Nicotiana benthamiana, we found that the
      UBD mediates the SLF protein turnover by the ubiquitin-proteasome pathway.
      Furthermore, we detected that the SLF protein was directly involved in S-RNase
      degradation. Taken together, our results provide a novel insight into the SLF
      structure and highlight a potential role of SLF protein stability and degradation
      in S-RNase-based self-incompatibility.

PMID- 22361509
TI  - Molecular cytogenetic characterization of wheat--Thinopyrum elongatum addition,
      substitution and translocation lines with a novel source of resistance to wheat
      Fusarium Head Blight.
AB  - Thinopyrum elongatum (2n=2x=14, EE), a wild relative of wheat, has been suggested
      as a potentially novel source of resistance to several major wheat diseases
      including Fusarium Head Blight (FHB). In this study, a series of wheat (cv.
      Chinese Spring, CS) substitution and ditelosomic lines, including Th. elongatum
      additions, were assessed for Type II resistance to FHB. Results indicated that
      the lines containing chromosome 7E of Th. elongatum gave a high level of
      resistance to FHB, wherein the infection did not spread beyond the inoculated
      floret. Furthermore, it was determined that the novel resistance gene(s) of 7E
      was located on the short-arm (7ES) based on sharp difference in FHB resistance
      between the two 7E ditelosomic lines for each arm. On the other hand, Th.
      elongatum chromosomes 5E and 6E likely contain gene(s) for susceptibility to FHB
      because the disease spreads rapidly within the inoculated spikes of these lines.
      Genomic in situ hybridization (GISH) analysis revealed that the alien chromosomes
      in the addition and substitution lines were intact, and the lines did not contain
      discernible genomic aberrations. GISH and multicolor-GISH analyses were further
      performed on three translocation lines that also showed high levels of resistance
      to FHB. Lines TA3499 and TA3695 were shown to contain one pair of wheat-Th.
      elongatum translocated chromosomes involving fragments of 7D plus a segment of
      the 7E, while line TA3493 was found to contain one pair of wheat-Th. elongatum
      translocated chromosomes involving the D- and A-genome chromosomes of wheat.
      Thus, this study has established that the short-arm of chromosome 7E of Th.
      elongatum harbors gene(s) highly resistant to the spreading of FHB, and chromatin
      of 7E introgressed into wheat chromosomes largely retained the resistance,
      implicating the feasibility of using these lines as novel material for breeding
      FHB-resistant wheat cultivars.

PMID- 22361510
TI  - Possible Involvement of Sphingosine-1-Phosphate/G(i)/RhoA pathways in adherence
      of eosinophils to pulmonary endothelium.
AB  - BACKGROUND: Sphingosine-1-phosphate (S1P), a lysophospholipid released from
      inflammatory cells, causes cell migration by increasing cytokines and chemokines.
      This study was designed to determine whether S1P causes adherence of eosinophils
      to pulmonary endothelial cells via enhancement of adhesion molecule expression.
      METHODS: Expression of VCAM-1 and ICAM-1 was assessed by RT-PCR and Western blot
      analysis in human pulmonary microvasucular endothelial cells (HPMVECs). The
      number of adherent eosinophils to HPMVECs was calculated according to adhesion
      assay. RESULTS: Pre-treatment of HPMVECs with S1P increased mRNA and protein
      expression of VCAM-1, in contrast, did not dramatically increase those expression
      of ICAM-1. The maximal expression of these adhesion molecules in mRNA and protein
      was observed 4 and 8h after exposure to S1P, respectively. Pre-treatment with S1P
      also activated RhoA, a monomeric G protein; the ability of S1P to enhance the
      expression of VCAM-1 was attenuated by RhoA related inhibitors such as Y-27632,
      C3 exoenzyme, and GGTI-286. The effects of S1P on VCAM-1 were attenuated by pre
      incubation with pertussis toxin, which catalyzes the ADP-ribosylation of G(i), a
      heterotrimeric G protein. After HPMVECs were treated with S1P, adhesion of human
      eosinophilic leukemic cell line (EoL-1) cells to HPMVECs was enhanced in a
      concentration-dependent manner. Augmented adherence of EoL-1 cells by S1P was
      also attenuated by Y-27632 and pertussis toxin. S1P causes adherence of
      eosinophils to pulmonary endothelium via RhoA activation. CONCLUSIONS: S1P may
      act as a lipid mediator in asthma. The RhoA/Rho-kinase pathway may be a
      therapeutic target for preventing eosinophil infiltration to the airway.

PMID- 22361511
TI  - Blood level of tacrolimus in patients with severe allergic conjunctivitis treated
      by 0.1% tacrolimus ophthalmic suspension.
AB  - BACKGROUND: To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic
      suspension based on the blood level of tacrolimus in patients with severe
      allergic conjunctivitis. METHODS: Fifty-two patients in whom topical anti
      allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic
      suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as
      well as ocular symptoms and signs. The blood concentration of tacrolimus was
      measured before the initiation of treatment and 4 and 12 weeks later. RESULTS:
      About 75% of the patients without concomitant using of tacrolimus ointment had
      blood levels of tacrolimus below the detection limit of the assay (0.5ng/mL). On
      the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using
      of tacrolimus ointment had blood levels above the detection limit of the assay.
      However, the maximum blood concentration was less than 2ng/mL. Adverse drug
      reactions occurred in 16 patients. These were disorders of the eye such as
      warmness, irritation, and a burning sensation. However, all of the patients could
      continue treatment with tacrolimus for 12 weeks. There were no serious adverse
      events such as increased intraocular pressure or ocular infection during the
      study. All symptoms and signs improved over time. CONCLUSIONS: The good safety
      profile of 0.1% tacrolimus ophthalmic suspension based on the low blood
      concentration of tacrolimus, coupled with demonstrated efficacy, make it an
      important tool for treating severe allergic conjunctivitis.

PMID- 22361512
TI  - Eleven cases of angioedema with eosinophilia treated in a single hospital in
      Japan.
AB  - BACKGROUND: Angioedema with eosinophilia (AE) is mostly reported in Japanese
      patients, and only as case reports. In this study, we aimed to determine how
      prevalent AE cases appear, the characteristic features and the course of AE, and
      to evaluate whether corticosteroid therapy for AE is necessary or not. METHODS:
      The patients whose blood samples showed an eosinophil count of >=2,000/MUL, among
      the samples tested for blood cell counts and differential counts between January
      2006 and December 2010, in Japanese Red Cross Medical Center, were firstly
      included. Among these, patients with AE were extracted. RESULTS: All of the 11
      patients were Japanese young females. One patient with arthralgia showed
      radioisotope accumulation in the joints by bone scintigraphy. The peak peripheral
      blood eosinophil count was 7,839 +/- 6,008 (2,130-23,170)/MUL after visiting our
      hospital. An increase in white blood cell count was only due to an increase in
      eosinophil count. Serum C-reactive protein and IgE levels remained almost normal.
      Peripheral blood eosinophil count decreased steadily for 8 weeks, regardless of
      corticosteroid use. Edema in all of the patients and arthralgia in 6 patients
      improved within 12 weeks. As far as followed, none of the patients had a
      recurrence of AE. CONCLUSIONS: AE developed in Japanese young females and likely
      showed a single course. In AE, the count of eosinophil of 104/MUL was observed.
      Only eosinophil count increased among leukocyte series. Serum C-reactive protein
      and IgE levels remained almost normal. The eosinophil count in AE patients will
      return to the normal level within 8 weeks even without corticosteroid therapy.

PMID- 22361513
TI  - ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously
      antigen- sensitized mice.
AB  - BACKGROUND: IL-33 is known to induce Th2-type cytokine production by various
      types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2
      and/or IL-33 genes was found in patients with atopic dermatitis and asthma,
      implying that the IL-33/ST2 pathway is closely associated with susceptibility to
      these diseases. Exposure to allergens through damaged skin is suspected to be a
      trigger for allergen sensitization, resulting in development of such allergic
      disorders as asthma and atopic dermatitis. METHODS: To elucidate the role(s) of
      the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously
      sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously
      sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA.
      The degree of airway inflammation, the number of leukocytes and the activities of
      myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage
      fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific
      IgE levels in sera were determined by histological analysis, a hemocytometer,
      colorimetric assay, quantitative PCR or ELISA, respectively. RESULTS: The number
      of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the
      lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced
      compared with wild-type mice. Although the number of neutrophils in BALFs and the
      pulmonary levels of IL-17 were comparable in both mice, the levels of MPO
      activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2
      /- mice. CONCLUSIONS: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated
      eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway
      inflammation in mice that had been epicutaneously sensitized with antigens and
      then challenged with antigen.

PMID- 22361514
TI  - Dissecting the causes of atopic dermatitis in children: less foods, more mites.
AB  - Atopic dermatitis (AD) is a common, chronic or chronically relapsing,
      multifactorial skin disease that mainly occurs in children but affects also
      adults. AD usually begins early in life and often concerns people with a personal
      or family history of asthma and allergic rhinitis. AD is characterized by
      eczematous changes in the epidermis and originates from a late, T-cell mediated
      reaction associated to the formation and production of memory T-cell of TH2 type,
      occurrence of homing receptor at skin level and cutaneous lymphocyte-associated
      (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total
      serum IgE levels and the presence of specific IgE for environmental and food
      allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a
      protein contained in the granular layer of the epidermis regulating the
      aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased
      barrier function of the corny layers of the epidermis. This favours  the enter
      through the skin of environmental allergens, especially the house dust mite, that
      further facilitates such entering by the proteolytic activity of its major
      allergen Der p 1. In fact, recent advances suggest that the dust mite, more than
      foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is
      concerned, there is notable evidence supporting the capacity of the atopy patch
      test (APT) to reproduce the pathophysiologic events of AD. This makes APT a
      valuable diagnostic tool for AD.

PMID- 22361515
TI  - Wiskott-Aldrich syndrome; an x-linked primary immunodeficiency disease with
      unique and characteristic features.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease
      with unique and characteristic features. In 1994, the responsible gene for WAS,
      the WASP gene on X-chromosome, was identified. Since then, renewed clinical and
      basic researches of WAS have started and remarkably developed. I will comment on
      recent progress in the clinical and basic researches of WAS, including some
      topics reported by our and other groups.

PMID- 22361518
TI  - Neuromuscular disorders in critically ill patients: review and update.
AB  - Neuromuscular disorders that are diagnosed in the intensive care unit (ICU)
      usually cause substantial limb weakness and contribute to ventilatory
      dysfunction. Although some lead to ICU admission, ICU-acquired disorders, mainly
      critical illness myopathy (CIM) and critical illness polyneuropathy (CIP), are
      more frequent and are associated with considerable morbidity. Approximately 25%
      to 45% of patients admitted to the ICU develop CIM, CIP, or both. Their clinical
      features often overlap; therefore, nerve conduction studies and electromyography
      are particularly helpful diagnostically, and more sophisticated electrodiagnostic
      studies and histopathologic evaluation are required in some circumstances. A
      number of prospective studies have identified risk factors for CIP and CIM, but
      their limitations often include the inability to separate CIM from CIP. Animal
      models reveal evidence of a channelopathy in both CIM and CIP, and human studies
      also identified axonal degeneration in CIP and myosin loss in CIM. Outcomes are
      variable. They tend to be better with CIM, and some patients have longstanding
      disabilities. Future studies of well-characterized patients with CIP and CIM
      should refine our understanding of risk factors, outcomes, and pathogenic
      mechanisms, leading to better interventions.

PMID- 22361519
TI  - Severe, focal tibialis anterior and triceps brachii weakness in myasthenia
      gravis: a case report.
AB  - We report a case of a patient with myasthenia gravis who presented with an
      atypically focal distribution of severe weakness in the triceps brachii and
      tibialis anterior muscles. Repetitive nerve stimulation studies demonstrated the
      typical decrement at rest, but also demonstrated marked facilitation after brief
      exercise. This case adds to the clinical and electrophysiological spectrum of
      variations of presentation of myasthenia gravis.

PMID- 22361516
TI  - Novel targeted therapies for mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy characterized by
      short median survival despite intensive therapies. The clinical behavior of MCL
      may be due to the complex pathophysiology of the disease which includes its
      genetic hallmark, the chromosomal translocation t(11;14) resulting in aberrant
      expression of cyclin D1, alteration in the DNA damage response, and constitutive
      activation of key anti-apoptotic pathways such as phosphatidyl-inositol 3-kinase
      (PI3K)/Akt and nuclear factor-kB (NF-kB). Collectively, these changes result in
      cell cycle dysregulation and give rise to profound genetic instability. Given
      this complex pathophysiology, the limited number of options for patients with
      relapsed/refractory MCL, and the difficulty in achieving long-lasting remissions
      with conventional approaches, it is essential to explore new treatment options
      targeting the numerous dysregulated pathways that are operable in MCL. We have
      recently reported that milatuzumab, a fully humanized anti-CD74 monoclonal
      antibody (mAb), in combination with anti-CD20 mAbs has significant preclinical
      and clinical activity in MCL. Here we discuss these results, provide additional
      insights into milatuzumab-mediated MCL cell death, and report preliminary data on
      the activity of other targeted biologic agents including PCI-32765 and CAL-101
      currently undergoing evaluation at our institution and others.

PMID- 22361520
TI  - Concurrent chronic motor axonal polyneuropathy and synaptic impairment of
      neuromuscular junction.
AB  - Polyneuropathies may exhibits clinical, electrophysiologic signs of neuromuscular
      junction impairment. Distal motor nerve terminals and neuromuscular junction
      contain pre or postsynaptically specific targets for circulating autoantibodies,
      if present in neuropathies. Motor nerve terminal blockade either reversible or
      permanent is a putative factor of muscle weakness. A 59-year-old patient
      exhibited oropharyngeal, facial, extremity weakness, fluctuating fatigability,
      and areflexia. Elecectrophysiologic studies showed purely motor axonal
      polyneuropathy. Thenar, facial slow rate repetitive stimulation revealed up to
      47% decrement of compound muscle action potential size. Single fiber
      electromyography on voluntary activation confirmed increased jitter and impulse
      blocking in all muscles examined in one third of the fibers. Repeated testings
      for antibodies to gangliosides, acetylcholine, muscle tyrosine kinase receptors,
      voltage-gated calcium channels were negative. Oral pyridostigmine bromide
      improved bulbar symptoms. Pulse intravenous immunoglobulin, oral steroids, and
      azathioprine had steady benefit. Impairment of neuromuscular transmission if
      occurring in chronic axonal neuropathies highlights mechanisms and significance
      of neuromuscular chronic "synaptopathies."

PMID- 22361521
TI  - Guillain-Barre syndrome after a jellyfish sting.
AB  - This is the case of a jellyfish sting associated with the rare development of
      Guillain-Barre syndrome. The patient, a 66-year-old woman, was stung by a
      jellyfish on the right thigh while swimming in the Atlantic Ocean, off
      Charleston, SC. Ten days later, she developed low back and right thigh pain
      followed by progressive numbness and weakness in all extremities. These symptoms
      reached their peak in 30 days and slowly began to improve. Initial neurologic
      examination showed areflexia, weakness, absent vibration and position sense, and
      hyperesthesia to pin and light touch in the mid to distal region of all four
      extremities. Serial electromyography and nerve conductions were consistent with
      an improving predominantly demyelinating polyneuropathy. Spinal fluid analysis
      showed no cells, elevated protein (108), gammaglobulin 6 (normal less than 5.4),
      and immunoglobulin G 8.2 (normal less than 6). The only treatment was gabapentin
      for neuropathy pain. The patient made an excellent recovery in less than 1 year
      with minimal residual numbness in both thumbs, index fingers, and middle toes.

PMID- 22361522
TI  - Vasculitic neuropathy associated with minocycline use.
AB  - INTRODUCTION: Minocycline is an antibiotic used for the treatment of acne. It has
      been associated with several autoimmune syndromes, including drug-induced lupus,
      autoimmune hepatitis, and vasculitis. METHOD AND RESULTS: We report a case of a
      28-year-old previously healthy woman who developed a left sciatic mononeuropathy
      2 weeks after starting minocycline for acne. Magnetic resonance imaging studies
      supported the localization. A biopsy of the left sural nerve revealed acute nerve
      large arteriole necrotizing vasculitis. Her condition improved after the
      withdrawal of minocycline and a course of treatment with methylprednisolone.
      CONCLUSION: This case provides further evidence that minocycline may induce a
      nonsystemic necrotizing vasculitis.

PMID- 22361523
TI  - Metabolic syndrome in small fiber sensory neuropathy.
AB  - OBJECTIVES: To determine the prevalence and risk of metabolic syndrome in
      patients with small fiber sensory neuropathy (SFSN). METHODS: We searched our
      skin biopsy database and identified 194 subjects for this retrospective study. Of
      these 194 subjects, 43 had normal skin biopsies and 151 had mild, moderate, or
      severe length-dependent SFSN with no large fiber involvement. Fifty-four subjects
      had diabetic or prediabetic SFSN and 97 had idiopathic SFSN. RESULTS: The mean
      age of the neuropathy group was older (54.1 +/- 11.9 years) than the normal
      biopsy group (44.8 +/- 13.0, P < 0.001). The prevalence of metabolic syndrome was
      higher in the neuropathy group (27.8%) than in the normal biopsy group (2.3%, P <
      0.001). Age was not different among three neuropathy subgroups. The prevalence of
      metabolic syndrome was higher in the severe (38.1%) than in the moderate (26.0%)
      and mild (14.7%) neuropathy groups (P = 0.04). Multivariate analysis revealed
      that age (odds ratio [OR], 1.95; P < 0.001), metabolic syndrome (OR, 3.20; P <
      0.001), hypertension (OR, 1.88; P = 0.04), and obesity (OR, 1.93; P = 0.004) were
      independent risk factors for SFSN. CONCLUSIONS: The prevalence of metabolic
      syndrome is increased in patients with SFSN and it correlates with the severity
      of SFSN. Metabolic syndrome may represent an independent risk factor for SFSN.

PMID- 22361517
TI  - Genetic determinants of the ankle-brachial index: a meta-analysis of a
      cardiovascular candidate gene 50K SNP panel in the candidate gene association
      resource (CARe) consortium.
AB  - BACKGROUND: Candidate gene association studies for peripheral artery disease
      (PAD), including subclinical disease assessed with the ankle-brachial index
      (ABI), have been limited by the modest number of genes examined. We conducted a
      two stage meta-analysis of ~50,000 SNPs across ~2100 candidate genes to identify
      genetic variants for ABI. METHODS AND RESULTS: We studied subjects of European
      ancestry from 8 studies (n=21,547, 55% women, mean age 44-73 years) and African
      American ancestry from 5 studies (n=7267, 60% women, mean age 41-73 years)
      involved in the candidate gene association resource (CARe) consortium. In each
      ethnic group, additive genetic models were used (with each additional copy of the
      minor allele corresponding to the given beta) to test each SNP for association
      with continuous ABI (excluding ABI>1.40) and PAD (defined as ABI<0.90) using
      linear or logistic regression with adjustment for known PAD risk factors and
      population stratification. We then conducted a fixed-effects inverse-variance
      weighted meta-analyses considering a p<2*10(-6) to denote statistical
      significance. RESULTS: In the European ancestry discovery meta-analyses,
      rs2171209 in SYTL3 (beta=-0.007, p=6.02*10(-7)) and rs290481 in TCF7L2 (beta=
      0.008, p=7.01*10(-7)) were significantly associated with ABI. None of the SNP
      associations for PAD were significant, though a SNP in CYP2B6 (p=4.99*10(-5)) was
      among the strongest associations. These 3 genes are linked to key PAD risk
      factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We
      sought replication in 6 population-based and 3 clinical samples (n=15,440) for
      rs290481 and rs2171209. However, in the replication stage (rs2171209, p=0.75;
      rs290481, p=0.19) and in the combined discovery and replication analysis the SNP
      ABI associations were no longer significant (rs2171209, p=1.14*10(-3); rs290481,
      p=8.88*10(-5)). In African Americans, none of the SNP associations for ABI or PAD
      achieved an experiment-wide level of significance. CONCLUSIONS: Genetic
      determinants of ABI and PAD remain elusive. Follow-up of these preliminary
      findings may uncover important biology given the known gene-risk factor
      associations. New and more powerful approaches to PAD gene discovery are
      warranted.

PMID- 22361524
TI  - A traumatic motor neuronopathy after a cervical burst fracture.

PMID- 22361525
TI  - Flunarizine-induced fasciculation-myokymia.

PMID- 22361528
TI  - Foreign bodies injuries: a strong unique pathway linking ORL and public health.

PMID- 22361529
TI  - An older profession yet.

PMID- 22361530
TI  - Processing errors.

PMID- 22361527
TI  - Toys in the upper aerodigestive tract: new evidence on their risk as emerging
      from the Susy Safe Study.
AB  - Foreign body (FB) inhalation, aspiration or ingestion are relatively common
      events in children. Despite many efforts made in several countries to achieve
      acceptable safety levels for consumer products devoted to children, small toys or
      toy parts are still frequently mentioned among risky foreign bodies. The aim of
      the present study is to characterize the risk of complications and prolonged
      hospitalization due to toys inhalation, aspiration or ingestion according to age
      and gender of patients, FB characteristics, circumstances of the accident, as
      emerging from the Susy Safe Registry. The Susy Safe Registry started in the 2005
      to collect data to serve as a basis for a knowledge-based consumer protection
      activity. It is actually one of the wider databases collecting foreign body
      injuries in the upper aero-digestive tract in pediatric patients. It is
      distinguished by a deep characterization of objects which caused the injuries and
      a multi-step quality control procedure which assures its reliability. Preventive
      strategies imposing a regulation of industrial production, even if fundamental,
      are not sufficient and need to be integrated along with other intervention
      addressed to make aware caregivers toward a proper surveillance of children.

PMID- 22361531
TI  - An impossible position.

PMID- 22361532
TI  - Crowding with tooth wear.

PMID- 22361544
TI  - Devoid of dentistry.
AB  - Dental curricula in UK dental schools are seemingly excising ever more skills as
      each generation of students is trained. This has implications for the quality of
      education held by the latest dental graduates, and furthermore potentially for
      the standard of care that their patients may receive. This leaves us today
      somewhat nostalgic for a bygone era when dental undergraduate education was
      replete with a fuller repertoire.

PMID- 22361545
TI  - What do we really know about UK paediatric dental general anaesthesia services?
AB  - Dental general anaesthesia (DGA) is only permitted within a hospital setting
      where critical care facilities are available. Recently, concern has been
      expressed about the number of hospital admissions for the dental care of children
      following the publication of a high profile paper which highlighted an apparent
      increase in children being admitted for extractions due to caries under DGA.
      Coincidentally new best practice standards for paediatric DGA services have been
      published. An evaluation of DGA services in Yorkshire and the Humber suggested
      that existing monitoring was inadequate and is unlikely to represent true levels
      of activity and that any apparent increase may reflect the method of remuneration
      for services. In fact, recent changes in service structure and changes to improve
      quality have reduced DGA activity in some areas. In addition, the evaluation
      revealed that many services were not meeting standards of best practice.

PMID- 22361546
TI  - Current concepts on the management of tooth wear: part 4. An overview of the
      restorative techniques and dental materials commonly applied for the management
      of tooth wear.
AB  - This final article of the four part series on the current concepts of tooth wear
      will provide the reader with an evaluation of the data available in the
      contemporary literature with regards to the survival analysis of differing
      restorative materials, and their respective methods of application to treat tooth
      wear. It is vital that the dental operator is familiar with the role of differing
      materials which may be used to restore the worn dentition, some of which may
      prove to be more suitable for the management of particular patterns of tooth wear
      than others. The active management of tooth wear unfortunately commits the
      patient to a lifelong need for considerable maintenance, and it is imperative
      that this is understood from the outset.

PMID- 22361547
TI  - Iatrogenic mandibular fractures following removal of impacted third molars: an
      analysis of 130 cases.
AB  - Immediate and late mandibular fractures are a rare complication of third molar
      removal. We analysed 130 cases of mandibular fractures following removal of
      impacted third molars reported in the literature, including four managed in the
      maxillofacial unit and identified potential risk factors. Its occurrence is
      likely to be multi-factorial, with age, gender, angulation, laterality, extent
      and degree of impaction and associated pathologies contributing to the risk of
      fracture. Postoperative fractures were more common than intra-operative fractures
      (2.7:1) and occurred most frequently in the second and third weeks (57%). A
      'cracking' noise was the most frequent presentation (77%). Intra-operative
      fractures were more frequent among females (M:F - 1:1.3), and differed from
      postoperative fractures (M:F - 3.9:1). This study analyses the results, providing
      suggestions to minimise the risk and to manage a mandibular fracture following
      removal of a third molar.

PMID- 22361552
TI  - Summary of: A comparative anthropometric study of the position of the mental
      foramen in three populations.
AB  - METHOD: The position of the mental foramen was recorded in relation to the
      mandibular teeth and anatomical landmarks on the mandible in 76 Chinese, 46
      European and 33 Indian skulls of known or calculated age at death. One way
      analysis of variance (ANOVA) with Tukey's test was used to compare the means of
      the three groups. RESULTS: The length of Indian mandibles was significantly
      smaller than that of Chinese (p <0.001) and European (p <0.05), but there was no
      significant difference between European and Chinese mandibles (p >0.05). The
      distance from the symphysis menti to the mental foramen was not significant in
      European and Indian mandibles (p >0.05), though the latter were significantly
      smaller than the Chinese (p <0.001). The distance from the mental foramen to the
      posterior border of the ramus of the mandible was significantly larger in Chinese
      and European skulls compared to that of Indian (p <0.01), there being no
      significant difference between European and Chinese (p >0.05). There was no
      significant difference in the relative position of the mental foramen (distance
      from symphysis menti to the mental foramen divided by the length of the mandible)
      between the Chinese and Indian mandibles (p >0.05) but there was a significant
      smaller difference between the European and both Chinese and Indian (p <0.001).
      The modal position of the foramen in the Chinese was in line with the long axis
      of the second premolar, while the European and Indian between the first and
      second premolar. CONCLUSION: The notion that the mental foramen lies between the
      first and second premolars can no longer be accepted. Population differences
      occur and preoperative radiographs are mandatory.

PMID- 22361553
TI  - Summary of: Tooth-whitening activity of a novel home-bleaching systemutilising
      thermal diffusion: a multifactorial simultaneous evaluation of efficacy at
      cervical, body and incisal tooth sites.
AB  - INTRODUCTION: The ability of a thermal diffusion system (TDS) to promote the
      tooth-whitening actions of a bleaching gel/bleaching activator combination
      product (containing a final hydrogen peroxide (H(2)O(2)) content of 10.0% (w/v))
      towards discoloured 'smile-zone' teeth was examined. METHODS: Fifty teeth in 15
      participants aged 18-62 years were investigated. The CIE tooth shade parameters
      L(*), a(*) and b(*), together with Vitapan shade scores (VSSs), were
      simultaneously recorded at three separate tooth areas (cervical, body and incisal
      sites) with a novel spectrophotometric monitoring system before treatment, and
      also at 14 days after completion of a 10-day treatment period in which the
      product was applied 'at-home' (twice daily). RESULTS: The tooth-whitening
      treatment administered gave rise to extremely significant increases in L(*), and
      decreases in the a(*) and b(*) shade parameters for each of the tooth areas
      investigated (p <10(-)10). Post-treatment mean decreases in the VSS values were
      8.26, 9.70 and 9.14 for the cervical, body and incisal areas respectively (p <10(
      8) in each case). Mean DeltaE values determined post-treatment were also very
      highly significant for each tooth region examined (p <10(-)10 in each case).
      CONCLUSIONS: The tooth-whitening system tested exerted extremely powerful
      bleaching actions in all tooth areas investigated. The order of tooth-whitening
      effectiveness was body > incisal > cervical for Deltab(*) and DeltaE, and incisal
      > body > cervical for Deltaa(*) and DeltaL(*), and this may reflect the TDS's
      ability to promote the penetration of H(2)O(2) to intrinsic stain sites.

PMID- 22361566
TI  - [First isolation in Spain of Aurantimonas altamirensis in a blood culture from a
      port-a-cath in a patient with Bence-Jones type multiple myeloma].

PMID- 22361567
TI  - [Severe Epstein Barr virus-related infectious mononucleosis in two brothers].

PMID- 22361569
TI  - Drugs for inflammatory bowel disease.

PMID- 22361568
TI  - Cupriavidus necator isolates are able to fix nitrogen in symbiosis with different
      legume species.
AB  - The aim of the present study was to identify a collection of 35 Cupriavidus
      isolates at the species level and to examine their capacity to nodulate and fix
      N(2). These isolates were previously obtained from the root nodules of two
      promiscuous trap species, Phaseolus vulgaris and Leucaena leucocephala,
      inoculated with soil samples collected near Sesbania virgata plants growing in
      Minas Gerais (Brazil) pastures. Phenotypic and genotypic methods applied for this
      study were SDS-PAGE of whole-cell proteins, and 16S rRNA and gyrB gene
      sequencing. To confirm the ability to nodulate and fix N(2), the presence of the
      nodC and nifH genes was also determined, and an experiment was carried out with
      two representative isolates in order to authenticate them as legume nodule
      symbionts. All 35 isolates belonged to the betaproteobacterium Cupriavidus
      necator, they possessed the nodC and nifH genes, and two representative isolates
      were able to nodulate five different promiscuous legume species: Mimosa
      caesalpiniaefolia, L. leucocephala, Macroptilium atropurpureum, P. vulgaris and
      Vigna unguiculata. This is the first study to demonstrate that C. necator can
      nodulate legume species.

PMID- 22361570
TI  - Crystal structures of a type-1 ribosome inactivating protein from Momordica
      balsamina in the bound and unbound states.
AB  - The ribosome inactivating proteins (RIPs) of type 1 are plant toxins that
      eliminate adenine base selectively from the single stranded loop of rRNA. We
      report six crystal structures, type 1 RIP from Momordica balsamina (A), three in
      complexed states with ribose (B), guanine (C) and adenine (D) and two structures
      of MbRIP-1 when crystallized with adenosine triphosphate (ATP) (E) and 2'
      deoxyadenosine triphosphate (2'-dATP) (F). These were determined at 1.67A, 1.60A,
      2.20A, 1.70A, 2.07A and 1.90A resolutions respectively. The structures contained,
      (A) unbound protein molecule, (B) one protein molecule and one ribose sugar, (C)
      one protein molecule and one guanine base, (D) one protein molecule and one
      adenine base, (E) one protein molecule and one ATP-product adenine molecule and
      (F) one protein molecule and one 2'-dATP-product adenine molecule. Three distinct
      conformations of the side chain of Tyr70 were observed with (i) chi(1)=-66
      degrees and chi(2)=165 degrees  in structures (A) and (B); (ii) chi(1)=-95
      degrees  and chi(2)=70 degrees  in structures (C), (D) and (E); and (iii) chi(1)=
      163 degrees  and chi(2)=87 degrees  in structure (F). The conformation of Tyr70
      in (F) corresponds to the structure of a conformational intermediate. This is the
      first structure which demonstrates that the slow conversion of DNA substrates by
      RIPs can be trapped during crystallization.

PMID- 22361571
TI  - Quantitative metrics of spinal cord injury recovery in the rat using motion
      capture, electromyography and ground reaction force measurement.
AB  - Toward improving the quantitative tools available for evaluation of locomotion
      after a spinal cord injury, we characterized selected biomechanical and
      physiological parameters that could be used to assess the level of recovery of
      locomotion after a mid-thoracic spinal cord lateral hemisection. Specifically we
      defined quantitative measures of muscle activation and coordination, body weight
      support, propulsive force, and pre-toe contact activation. Generation of this
      ensemble of recovery measures was based on kinematics, ground reaction forces,
      and EMG in rats from the hindlimb ipsilateral to the hemisection during
      quadrupedal running on a trackway. We derived muscle activation levels using
      inverse dynamics and static optimization applied to a model of the hindlimb
      musculoskeletal system. Rats exhibited a phased recovery pattern: progressive
      recovery of general muscle activity beginning within 2-3 days post-injury,
      followed by recovery of propulsive force and intralimb coordination of
      antagonistic muscles 12-13 days post-injury. Even at 12-13 days post-injury
      however, body weight support and the normal pre-paw contact EMG burst were
      significantly impaired. These data are consistent with a differential rate of
      recovery of general motor pool recruitment, and coordination among motor pools.
      The results demonstrate the discriminative potential of these physiologically
      based measures in quantifying the progressive recovery of gait performance after
      a lateral spinal cord hemisection.

PMID- 22361572
TI  - Detecting synfire chains in parallel spike data.
AB  - The synfire chain model of brain organization has received much theoretical
      attention since its introduction (Abeles, 1982, 1991). However there has been no
      convincing experimental demonstration of synfire chains due partly to limitations
      of recording technology but also due to lack of appropriate analytic methods for
      large scale recordings of parallel spike trains. We have previously published one
      such method based on intersection of the neural populations active at two
      different times (Schrader et al., 2008). In the present paper we extend this
      analysis to deal with higher firing rates and noise levels, and develop two
      additional tools based on properties of repeating firing patterns. All three
      measures show characteristic signatures if synfire chains underlie the recorded
      data. However we demonstrate that the detection of repeating firing patterns
      alone (as used in several papers) is not enough to infer the presence of synfire
      chains. Positive results from all three measures are needed.

PMID- 22361573
TI  - Early urinary aldosterone excretion in very low birth weight infants.
AB  - HYPOTHESIS/ INTRODUCTION: In the neonatal period, many factors may interfere with
      aldosterone production but data currently available are few and controversial. In
      this study we aim to assess the early urinary aldosterone excretion (UAE) in very
      low birth weight (VLBW) infants and to identify some possible clinical and
      biochemical variables that may influence this excretion. MATERIALS AND METHODS:
      We conducted a prospective study in 30 VLBW infants. Aldosterone was measured in
      the first 72 hours of life in the urine and plasma and urinary electrolytes were
      determined. Demographic and clinical data were also recorded. RESULTS: The
      exploratory analysis showed that a significant positive correlation exists
      between UAE and gestational age and birth weight and that infants with
      respiratory distress syndrome have higher urinary aldosterone levels than infants
      without respiratory distress, but only plasma sodium resulted a significant
      independent factor that negatively influenced UAE at linear regression analysis
      (coefficient -0.02, 95% confidence interval [-0.03; -0.004]; adjusted R(2) 0.33).
      CONCLUSIONS: The renin-angiotensin-aldosterone system of VLBW infants seems to be
      able, even immediately after birth, to respond to variations of plasma sodium
      concentrations; measurement of UAE constitutes an interesting method to determine
      aldosterone production, avoiding blood sampling in neonates so small and frail as
      VLBW infants.

PMID- 22361574
TI  - Extracorporeal photopheresis: the Hellenic experience.

PMID- 22361575
TI  - DNA nanotube formation based on normal mode analysis.
AB  - Ever since its inception, a popular DNA motif called the cross tile has been
      recognized to self-assemble into addressable 2D templates consisting of periodic
      square cavities. Although this may be conceptually correct, in reality certain
      types of cross tiles can only form planar lattices if adjacent tiles are designed
      to bind in a corrugated manner, in the absence of which they roll up to form 3D
      nanotube structures. Here we present a theoretical study on why uncorrugated
      cross tiles self-assemble into counterintuitive 3D nanotube structures and not
      planar 2D lattices. Coarse-grained normal mode analysis of single and multiple
      cross tiles within the elastic network model was carried out to expound the
      vibration modes of the systems. While both single and multiple cross tile
      simulations produce results conducive to tube formations, the dominant modes of a
      unit of four cross tiles (one square cavity), termed a quadruplet, fully reflect
      the symmetries of the actual nanotubes found in experiments and firmly endorse
      circularization of an array of cross tiles.

PMID- 22361576
TI  - Reliability and structural validity of the Multidimensional Fatigue Inventory
      (MFI) in patients with idiopathic Parkinson's disease.
AB  - INTRODUCTION: The Multidimensional Fatigue Inventory (MFI) is commonly used in
      patients with Parkinson's disease (PD). However, most measurement properties have
      not been investigated in this population. The aim of this study was to
      investigate internal consistency, test-retest reliability, measurement error,
      structural validity, and floor and ceiling effects of the MFI in PD. METHODS:
      Patients with PD (N = 153) completed the MFI at baseline and week 3 in a
      randomized clinical trial. Cronbach's alpha, intraclass correlation coefficient
      (ICC), and the smallest detectable change (SDC) were calculated. Bland and Altman
      analysis was performed. Principal Component Analysis (PCA) was used to explore
      structural validity. Floor and ceiling effects were investigated. RESULTS:
      Cronbach's alpha for the MFI-total and subscales ranged from 0.74 (reduced
      motivation (RM)) to 0.92 (MFI-total). ICC's ranged from 0.65 (mental fatigue (MF)
      to 0.81 (physical fatigue (PF)), SDC ranged from 4 points (PF and RM) to 15
      points (MFI-total). Bland and Altman analysis showed no systematic differences
      between assessments. A floor effect was found for MF and ceiling effects for PF
      and reduced activity (RA). A four-factor model was extracted, combining general
      fatigue (GF) and PF as one factor. CONCLUSIONS: The MFI is reliable and valid to
      assess fatigue in patients with PD. Clinicians and researchers interested in
      assessing specific aspects of fatigue should consider interpreting GF and PF as
      one subscale measuring physical aspects of fatigue. To establish whether the MFI
      can detect meaningful changes, studies on anchor-based responsiveness and the
      minimal important change are needed in PD.

PMID- 22361577
TI  - PARK2 variability in Polish Parkinson's disease patients--interaction with
      mitochondrial haplogroups.
AB  - AIMS AND OBJECTIVES: A new pathomechanism of Parkinson's disease (PD) involving
      regulation of mitochondrial functions was recently proposed. Parkin complexed
      with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes
      mitochondrial biogenesis, which is abolished by PARK2 gene mutations. We have
      previously shown that mitochondrial haplogroups/clusters and TFAM common
      variation influenced PD risk. We investigate the role of PARK2 polymorphisms on
      PD risk and their interactions with mitochondrial haplogroups/clusters as well as
      with TFAM variability. METHODS: 104 early-onset PD patients (EOPD, age at onset
      <= 50 years) were screened for PARK2 coding sequence changes including gene
      dosage alterations. Three selected PARK2 polymorphisms (S167N, V380L, D394N) were
      genotyped in 326 PD patients and 315 controls using TaqMan allelic discrimination
      assay. RESULTS: PARK2 screen revealed two heterozygous changes in two EOPD
      patients: exon 2 deletion and one novel synonymous variation (c.999C > A, P333P).
      In association study no differences in genotype/allele frequencies of S167N,
      V380L, D394N were found between analyzed groups. Stratification by mitochondrial
      clusters revealed higher frequency of V380L G/G genotype and allele G in PD
      patients, within HV cluster (p = 0.040; p = 0.022, respectively). Moreover,
      interaction between genotypes G/G V380L of PARK2 and G/G rs2306604 of TFAM,
      within HV cluster was significant (OR 2.05; CI 1.04-4.04; p = 0.038).
      CONCLUSIONS: Our results indicate that co-occurrence of G/G V380L PARK2 and G/G
      rs2306604 TFAM on the prooxidative HV cluster background can contribute to PD
      risk. We confirm low PARK2 mutation frequency in Polish EOPD patients.

PMID- 22361578
TI  - SNARE Dance: a musical interpretation of Atg9 transport to the tubulovesicular
      cluster.
AB  - There is little doubt that humans rely on vision as their primary sensory input.
      However, various studies indicate that audiovisual combinations of data
      presentation actually enhance the ability of the learner to comprehend the
      information. We present an example of a musical-biological interface that
      provides an audible demonstration of SNARE protein function in the process of
      macroautophagy.

PMID- 22361579
TI  - Role of ATG3 in the parasite Toxoplasma gondii: autophagy in an early branching
      eukaryote.
AB  - Toxoplasma gondii belongs to the phylum Apicomplexa, a diverse group of early
      branching unicellular eukaryotes related to dinoflagellates and ciliates. Like
      several other Apicomplexa such as Plasmodium (the causative agent of malaria), T.
      gondii is a human pathogen responsible for a potentially lethal disease called
      toxoplasmosis. Most Apicomplexa have complex life cycles, involving intermediate
      hosts and vectors, which include obligatory intracellular developmental stages.
      In the case of malaria and toxoplasmosis, it is that replicative process, leading
      to the ultimate lysis of the host cell, which is causing the symptoms of the
      disease. For Toxoplasma, the invasive and fast-replicating form of the parasite
      is called the tachyzoite. While autophagy has been a fast-growing field of
      research in recent years, not much was known about the relevance of this
      catabolic process in medically important apicomplexan parasites. Vesicles
      resembling autophagosomes had been described in drug-treated Plasmodium parasites
      in the early 1970s and a potential role for autophagy in organelle recycling
      during differentiation between Plasmodium life stages has also been recently
      described. Interestingly, recent database searches have identified putative
      orthologs of the core machinery responsible for the formation of autophagosomes
      in several protists, including Toxoplasma. In spite of an apparently reduced
      machinery (only about one-third of the yeast ATG genes appear to be conserved),
      T. gondii seemed thus able to perform macroautophagy, but the cellular functions
      of the pathway for this parasite remained to be demonstrated.

PMID- 22361580
TI  - Processing of proteins in autophagy vesicles of antigen-presenting cells
      generates citrullinated peptides recognized by the immune system.
AB  - Our laboratory has been investigating for some time the nature of the response of
      T lymphocytes in autoimmunity in the reactions against self-proteins that result
      in a number of diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid
      arthritis (RA) and others. T cells recognize peptides generated from proteins
      that are processed by antigen-presenting cells (APC). The peptides may derive
      from exogenous proteins or from the normal catabolism of self-proteins. The
      peptides complexed to major histocompatibility complex (MHC) molecules constitute
      the chemical entity that is engaged by the antigen-receptor of T cells. An
      important hypothesis postulates that self-peptides that suffer post-translational
      modifications in the APC may form neo-antigens that are recognized by the immune
      system and form the target of autoimmunity. Our interest in citrullination in the
      context of antigen processing and presentation stemmed from studies suggesting
      that an immune response to citrullinated self-peptides may be involved in
      autoimmunity. In a first publication, we found T cells that specifically
      recognized citrullinated peptides after immunization of inbred mice with standard
      foreign proteins. We used the small protein hen-egg white lysozyme. These T cells
      only recognized the citrullinated peptide and not the unmodified one, thus
      proving that a neo-epitope had been created by this modification. But how this
      modification took place was not known. Our recent report describes a central role
      for autophagy in citrullination of peptides by APC.

PMID- 22361581
TI  - alpha-Synuclein levels affect autophagosome numbers in vivo and modulate
      Huntington disease pathology.
AB  - Huntington and Parkinson diseases (HD and PD) are two major neurodegenerative
      disorders pathologically characterized by the accumulation of the aggregate-prone
      proteins mutant huntingtin (in HD) and alpha-synuclein (in PD). Mutant huntingtin
      is an autophagy substrate and autophagy modulators affect HD pathology both in
      vitro and in vivo. In vitro, alpha-synuclein levels are able to modulate
      autophagy: alpha-synuclein overexpression inhibits autophagy, whereas
      downregulation promotes autophagy. Here, we review our recent studies showing
      that alpha-synuclein levels modulate mutant huntingtin toxicity in mouse models.
      This phenotypic modification is accompanied by the in vivo modulation of
      autophagosome numbers in mouse brains from both control and HD mice expressing
      different levels of alpha-synuclein.

PMID- 22361582
TI  - Allophagy: a macroautophagic process degrading spermatozoid-inherited organelles.
AB  - In most animals, during oocyte fertilization the spermatozoon provides DNA and
      centrioles together with some cytoplasm and organelles, but paternal mitochondria
      are generally eliminated in the embryo. Using the model animal C. elegans we have
      shown that paternal organelle degradation is dependent on the formation of
      autophagosomes a few minutes after fertilization. This macroautophagic process is
      preceded by an active ubiquitination of some spermatozoon-inherited organelles.
      Analysis of fertilized mouse embryos suggests that this autophagy event is
      evolutionarily conserved.

PMID- 22361583
TI  - alpha-Synuclein fate: proteasome or autophagy?
AB  - The accumulation of alpha-synuclein is critical for the development of Parkinson
      disease (PD), and unraveling the mechanisms that regulate alpha-synuclein levels
      is key to understanding the pathophysiology of the disease. We recently found
      that USP9X deubiquitinates alpha-synuclein, and that this process determines the
      partition of alpha-synuclein between the proteasomal and autophagy pathways. By
      manipulating USP9X levels, we observed that monoubiquitinated alpha-synuclein is
      degraded by the proteasome, whereas deubiquitination of alpha-synuclein favors
      its degradation by autophagy. As USP9X levels and activity are decreased in alpha
      synucleinopathy brains, USP9X may now represent a novel target for PD.

PMID- 22361584
TI  - Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer
      cell death.
AB  - One particular strategy to render anticancer therapies efficient consists of
      converting the patient's own tumor cells into therapeutic vaccines, via the
      induction of immunogenic cell death (ICD). One of the hallmarks of ICD dwells in
      the active release of ATP by cells committed to undergo, but not yet having
      succumbed to, apoptosis. We observed that the knockdown of essential autophagy
      related genes (ATG3, ATG5, ATG7 and BECN1) abolishes the pre-apoptotic secretion
      of ATP by several human and murine cancer cell lines undergoing ICD. Accordingly,
      autophagy-competent, but not autophagy-deficient, tumor cells treated with ICD
      inducers in vitro could induce a tumor-specific immune response in vivo. Cancer
      cell lines stably depleted of ATG5 or ATG7 normally generate tumors in vivo, and
      such autophagy-deficient neoplasms, upon systemic treatment with ICD inducers,
      exhibit the same levels of apoptosis (as monitored by nuclear shrinkage and
      caspase-3 activation) and necrosis (as determined by following the kinetics of
      HMGB1 release) as their autophagy-proficient counterparts. However, autophagy
      incompetent cancers fail to release ATP, to recruit immune effectors into the
      tumor bed and to respond to chemotherapy in conditions in which autophagy
      competent tumors do so. The intratumoral administration of ecto-ATPase inhibitors
      increases extracellular ATP concentrations, re-establishes the therapy-induced
      recruitment of dendritic cells and T cells into the tumor bed, and restores the
      chemotherapeutic response of autophagy-deficient cancers. Altogether, these
      results suggest that autophagy-incompetent tumor cells escape from chemotherapy
      induced (and perhaps natural?) immunosurveillance because they are unable to
      release ATP.

PMID- 22361586
TI  - Prioritising pharmaceuticals for environmental risk assessment: Towards adequate
      and feasible first-tier selection.
AB  - The presence of pharmaceuticals in the aquatic environment, and the concerns for
      negative effects on aquatic organisms, has gained increasing attention over the
      last years. As ecotoxicity data are lacking for most active pharmaceutical
      ingredients (APIs), it is important to identify strategies to prioritise APIs for
      ecotoxicity testing and environmental monitoring. We have used nine previously
      proposed prioritisation schemes, both risk- and hazard-based, to rank 582 APIs.
      The similarities and differences in overall ranking results and input data were
      compared. Moreover, we analysed how well the methods ranked seven relatively well
      studied APIs. It is concluded that the hazard-based methods were more successful
      in correctly ranking the well-studied APIs, but the fish plasma model, which
      includes human pharmacological data, also showed a high success rate. The results
      of the analyses show that the input data availability vary significantly; some
      data, such as logP, are available for most API while information about
      environmental concentrations and bioconcentration are still scarce. The results
      also suggest that the exposure estimates in risk-based methods need to be
      improved and that the inclusion of effect measures at first-tier prioritisation
      might underestimate risks. It is proposed that in order to develop an adequate
      prioritisation scheme, improved data on exposure such as degradation and sewage
      treatment removal and bioconcentration ability should be further considered. The
      use of ATC codes may also be useful for the development of a prioritisation
      scheme that includes the mode of action of pharmaceuticals and, to some extent,
      mixture effects.

PMID- 22361585
TI  - Autophagy regulates endoplasmic reticulum stress in ischemic preconditioning.
AB  - Recent studies have suggested that autophagy plays a prosurvival role in ischemic
      preconditioning (IPC). This study was taken to assess the linkage between
      autophagy and endoplasmic reticulum (ER) stress during the process of IPC. The
      effects of IPC on ER stress and neuronal injury were determined by exposure of
      primary cultured murine cortical neurons to 30 min of OGD 24 h prior to a
      subsequent lethal OGD. The effects of IPC on ER stress and ischemic brain damage
      were evaluated in rats by a brief ischemic insult followed by permanent focal
      ischemia (PFI) 24 h later using the suture occlusion technique. The results
      showed that both IPC and lethal OGD increased the LC3-II expression and decreased
      p62 protein levels, but the extent of autophagy activation was varied. IPC
      treatment ameliorated OGD-induced cell damage in cultured cortical neurons,
      whereas 3-MA (5-20 mM) and bafilomycin A 1 (75-150 nM) suppressed the
      neuroprotection induced by IPC. 3-MA, at the dose blocking autophagy,
      significantly inhibited IPC-induced HSP70, HSP60 and GRP78 upregulation;
      meanwhile, it also aggregated the ER stress and increased activated caspase-12,
      caspase-3 and CHOP protein levels both in vitro and in vivo models. The ER stress
      inhibitor Sal (75 pmol) recovered IPC-induced neuroprotection in the presence of
      3-MA. Rapamycin 50-200 nM in vitro and 35 pmol in vivo 24 h before the onset of
      lethal ischemia reduced ER stress and ischemia-induced neuronal damage. These
      results demonstrated that pre-activation of autophagy by ischemic preconditioning
      can boost endogenous defense mechanisms to upregulate molecular chaperones, and
      hence reduce excessive ER stress during fatal ischemia.

PMID- 22361587
TI  - Sewer epidemiology mass balances for assessing the illicit use of
      methamphetamine, amphetamine and tetrahydrocannabinol.
AB  - In sewer epidemiology, mass balances are used to back-extrapolate measurements of
      wastewater influent concentrations of appropriate drug residues to assess the
      parent illicit drug's level of use in upstream populations. This study focussed
      on developing and refining mass balances for the use of illicit methamphetamine,
      amphetamine and tetrahydrocannabinol. As a first step, a multi-criteria
      evaluation was used to select unchanged methamphetamine, unchanged amphetamine
      and 11-nor-9-carboxy-tetrahydrocannabinol as the most appropriate drug residues
      to track a selected population's use of illicit methamphetamine, amphetamine and
      tetrahydrocannabinol, respectively. For each of these selected drug residues,
      mass balances were developed by utilizing all disposition data available for
      their release from all their respective sources, incorporating route-of
      administration considerations where relevant, and accounting for variations in
      the metabolic capacity of users of the various relevant licit and illicit
      sources. Further, since the selected drug residues for the use of methamphetamine
      and amphetamine cannot only result from their use but numerous other licit and
      illicit sources, comprehensive general source models were developed for their
      enantiomeric-specific release to sewers. The relative importance of the sources
      identified in the general source model was evaluated by performing national
      substance flow analyses for a number of countries. Results suggested that licit
      sources of methamphetamine are expected to be only of significance in populations
      where its illicit use is minor. Similarly, in populations where the use of
      illicitly produced amphetamine is currently of relevance, licit contributions to
      the sewer loads of amphetamine are likely to be of negligible importance. Lastly,
      the study of tetrahydrocannabinol back-extrapolation mass balances suggested that
      further research is required to assess the importance of fecal elimination of 11
      nor-9-carboxy-tetrahydrocannabinol.

PMID- 22361588
TI  - Discussion on paper entitled "Migration behaviour, of landfill leachate
      contaminants through alternative composite liners" by G. Varank, A. Demir, E.
      Sekman, A. Akkaya, K. Yetilezsoy, M.S. Bilgili.

PMID- 22361589
TI  - The safety profile of home infusion of intravenous immunoglobulin in patients
      with neuroimmunologic disorders.
AB  - OBJECTIVES: To assess the overall safety of high-dose intravenous immunoglobulin
      (IG) products used to treat patients with neuroimmunological disorders in a
      supervised home-based setting. METHODS: The incidence of adverse reactions was
      assessed in a retrospective chart review of 420 patients who consecutively
      received 4076, home-based, individual, intravenous immunoglobulin (IVIG)
      infusions between January 2009 and December 2009. RESULTS: A total of 90 patients
      (21.4%) developed adverse reactions related to IVIG administration (2.6% per
      individual infusion). A total of 95.5% of adverse reactions were mild, and no
      serious side effects were observed. The incidence of adverse reactions was
      significantly lower in the subgroup of patients with neuroimmunological disorders
      who received premedication (18.2% compared with 29.3%, P = 0.02). There was no
      significant statistical difference in the incidence of side effects among the
      different brands of IVIG used in this study. CONCLUSIONS: The combination of
      premedication and well-defined clinical, IVIG infusion policies may reduce the
      incidence of high-dose IVIG adverse reactions administered in a home-based
      setting in patients with neuroimmunological disorders.

PMID- 22361590
TI  - Sniffing out pharmacology: interactions of drugs with human olfaction.
AB  - Advances in the understanding of the sense of smell have increased awareness of
      the role of olfaction in human life. Odors are perceived via specific G protein
      coupled receptors (GPCRs) with cAMP as the second messenger. Drugs that interact
      with this signaling cascade, such as opioids, cannabinoids and sildenafil, are
      known to reduce olfactory function. Drugs that are active in the central nervous
      system (CNS) may also hinder the complex processing of olfactory information to
      distinguish, via pattern recognition, thousands of odors from the signals of only
      ~400 distinct olfactory receptors. Many other interactions with drug targets
      expressed at the olfactory bulb are also likely to occur. However, olfactory drug
      effects have rarely been explored in controlled studies. In the current
      activities of drug development and re-purposing, olfaction could become highly
      important because it can impact significantly upon the enjoyment of food. With an
      established molecular basis and using available tools, the assessment of
      olfaction in drug development and approval is advised.

PMID- 22361593
TI  - Eco efficiency, a path towards integrated resource management.

PMID- 22361591
TI  - NMR structures of the transmembrane domains of the alpha4beta2 nAChR.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the predominant
      heteromeric subtype of nAChRs in the brain, which has been implicated in numerous
      neurological conditions. The structural information specifically for the
      alpha4beta2 and other neuronal nAChRs is presently limited. In this study, we
      determined structures of the transmembrane (TM) domains of the alpha4 and beta2
      subunits in lauryldimethylamine-oxide (LDAO) micelles using solution NMR
      spectroscopy. NMR experiments and size exclusion chromatography-multi-angle light
      scattering (SEC-MALS) analysis demonstrated that the TM domains of alpha4 and
      beta2 interacted with each other and spontaneously formed pentameric assemblies
      in the LDAO micelles. The Na(+) flux assay revealed that alpha4beta2 formed Na(+)
      permeable channels in lipid vesicles. Efflux of Na(+) through the alpha4beta2
      channels reduced intra-vesicle Sodium GreenTM fluorescence in a time-dependent
      manner that was not observed in vesicles without incorporating alpha4beta2. The
      study provides structural insight into the TM domains of the alpha4beta2 nAChR.
      It offers a valuable structural framework for rationalizing extensive biochemical
      data collected previously on the alpha4beta2 nAChR and for designing new
      therapeutic modulators.

PMID- 22361592
TI  - Gain-of-function p53 mutants have widespread genomic locations partially
      overlapping with p63.
AB  - p53 and p63 are transcription factors -TFs- playing master roles in the DNA
      damage response and in the development and maintenance of pluristratified
      epithelia, respectively. p53 mutations are common in epithelial tumors and HaCaT
      keratinocytes harbor two p53 alleles -H179Y and R282Q- with gain-of-function
      (GOF) activity. Indeed, functional inactivation of mutp53 affects the growth rate
      of HaCaT. We investigated the strategy of mutp53, by performing ChIP-Seq
      experiments of mutp53 and p63 and analyzed the transcriptome after mutp53
      inactivation. Mutp53 bind to 7135 locations in vivo, with a robust overlap with
      p63. De novo motifs discovery recovered a p53/p63RE with high information content
      in sites bound by p63 and mutp53/p63, but not by mutp53 alone: these sites are
      rather enriched in elements of other TFs. The HaCaT p63 locations are only
      partially overlapping with those of normal keratinocytes; importantly, and
      enriched in mutp53 sites which delineate a functionally different group of target
      genes. Our data favour a model whereby mutp53 GOF mutants act both by tethering
      growth-controlling TFs and highjacking p63 to new locations.

PMID- 22361594
TI  - Application of a simplified mathematical model to estimate the effect of forced
      aeration on composting in a closed system.
AB  - The aeration rate is a key process control parameter in the forced aeration
      composting process because it greatly affects different physico-chemical
      parameters such as temperature and moisture content, and indirectly influences
      the biological degradation rate. In this study, the effect of a constant airflow
      rate on vertical temperature distribution and organic waste degradation in the
      composting mass is analyzed using a previously developed mathematical model of
      the composting process. The model was applied to analyze the effect of two
      different ambient conditions, namely, hot and cold ambient condition, and four
      different airflow rates such as 1.5, 3.0, 4.5, and 6.0 m(3) m(-2) h(-1),
      respectively, on the temperature distribution and organic waste degradation in a
      given waste mixture. The typical waste mixture had 59% moisture content and 96%
      volatile solids, however, the proportion could be varied as required. The results
      suggested that the model could be efficiently used to analyze composting under
      variable ambient and operating conditions. A lower airflow rate around 1.5-3.0
      m(3) m(-2) h(-1) was found to be suitable for cold ambient condition while a
      higher airflow rate around 4.5-6.0 m(3) m(-2) h(-1) was preferable for hot
      ambient condition. The engineered way of application of this model is flexible
      which allows the changes in any input parameters within the realistic range. It
      can be widely used for conceptual process design, studies on the effect of
      ambient conditions, optimization studies in existing composting plants, and
      process control.

PMID- 22361595
TI  - Principles of percutaneous paravalvular leak closure.
AB  - Paravalvular regurgitation affects 5% to 17% of all surgically implanted
      prosthetic heart valves. Patients who have paravalvular regurgitation can be
      asymptomatic or present with hemolysis or heart failure, or both. Reoperation is
      associated with increased morbidity and is not always successful because of
      underlying tissue friability, inflammation, or calcification. Comprehensive
      echocardiographic imaging with transthoracic and real-time 3-dimensional
      transesophageal echocardiography is key for characterizing the defect location,
      size, and shape. For paramitral defects, an antegrade transseptal approach can
      usually be guided by biplane fluoroscopy, and real-time 3-dimensional
      transesophageal echocardiography can usually be performed successfully.
      Alternative approaches to paramitral defects include retrograde transaortic
      cannulation or transapical access and retrograde cannulation. For oblong or
      crescentic defects, the simultaneous or sequential deployment of 2 smaller
      devices, as opposed to 1 large device, results in a higher degree of procedural
      success and safety because the risk of impingement on the prosthetic leaflets is
      minimized. Most para-aortic defects can be approached in a retrograde manner and
      closed with a single device. With careful anatomical assessment, procedural
      planning, and procedural execution, successful closure rates of 90% or more
      should be attainable with a low risk of device impingement on the prosthetic
      valve or embolization.

PMID- 22361596
TI  - Clinical presentation, management, and outcomes of angiographically documented
      early, late, and very late stent thrombosis.
AB  - OBJECTIVES: The aim of this study was to describe differences in treatment and in
      hospital mortality of early, late, and very late stent thrombosis (ST).
      BACKGROUND: Early, late, and very late ST may differ in clinical presentation,
      management, and in-hospital outcomes. METHODS: We analyzed definite
      (angiographically documented) ST cases identified from February 2009 to June 2010
      in the CathPCI Registry. We stratified events by timing of presentation: early
      (<=1 month), late (1 to 12 months), or very late (>=12 months) following stent
      implantation. Multivariable logistic regression modeling was performed to compare
      in-hospital mortality for each type of ST after adjusting for baseline
      comorbidities. RESULTS: During the study period, 7,315 ST events were identified
      in 7,079 of 401,662 patients (1.8%) presenting with acute coronary syndromes.
      This ST cohort consisted of 1,391 patients with early ST (19.6%), 1,370 with late
      ST (19.4%), and 4,318 with very late ST (61.0%). Subjects with early ST had a
      higher prevalence of black race and diabetes, whereas subjects with very late ST
      had a higher prevalence of white race and a lower prevalence of prior myocardial
      infarction or diabetes. In-hospital mortality was significantly higher in early
      ST (7.9%) compared with late (3.8%) and very late ST (3.6%, p<0.001). This lower
      mortality for late and very late ST persisted after multivariable adjustment
      (odds ratio: 0.53 [95% confidence interval (CI): 0.36 to 0.79] and 0.58 [95% CI:
      0.43 to 0.79], respectively). CONCLUSIONS: Significant differences exist in the
      presentation and outcomes of early, late, and very late ST. Among patients with
      acute coronary syndromes who are undergoing percutaneous coronary intervention
      for angiographically documented ST, early ST is associated with the highest in
      hospital mortality.

PMID- 22361597
TI  - New insights on stent thrombosis: in praise of large nationwide registries for
      rare cardiovascular events.

PMID- 22361598
TI  - Long-term comparison of everolimus- and sirolimus-eluting stents in patients with
      acute coronary syndromes.
AB  - OBJECTIVES: The goal of this study was to compare the long-term clinical outcome
      between everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) in
      patients with acute coronary syndromes (ACS). BACKGROUND: EES have not been
      directly compared with SES in ACS patients to date. METHODS: Between 2004 and
      2009, 1,746 consecutive ACS patients (ST-segment elevation ACS [STE-ACS]: 33.5%;
      non-ST-segment elevation ACS [NSTE-ACS]: 66.5%) were treated with EES (n=903) or
      SES (n=843). Using propensity score matching, clinical outcome was compared among
      705 matched pairs of ACS patients treated with EES and SES. RESULTS: Through 3
      years, the primary endpoint-the composite of death, myocardial infarction (MI),
      and target vessel revascularization (TVR)-occurred in 13.8% of EES- and 17.7% of
      SES-treated ACS patients (hazard ratio [HR]: 0.72, 95% confidence interval [CI]:
      0.54 to 0.95, p=0.02). The difference in favor of EES was driven by a lower risk
      of TVR (5.7% vs. 8.8%, HR: 0.65, 95% CI: 0.43 to 0.98, p=0.04) and a trend toward
      a lower risk of MI (2.1% vs. 3.3%, HR: 0.56, 95% CI: 0.29 to 1.12, p=0.10). The
      risk of death (7.2% vs. 8.8%, HR: 0.75, 95% CI: 0.50 to 1.10, p=0.14) showed no
      difference between EES and SES. The treatment effect in favor of EES for the
      primary endpoint was similar for patients with STE-ACS (16.4% vs. 18.5%, HR:
      0.80, 95% CI: 0.50 to 1.27) and NSTE-ACS (12.4% vs. 17.3%; HR: 0.67, 95% CI: 0.47
      to 0.96; pfor interaction=0.56) and across major subgroups. Definite (0.4% vs.
      1.8%, p=0.03), and definite or probable stent thrombosis (3.4% vs. 6.1%, p=0.02)
      were less frequent among EES- than SES-treated ACS patients. CONCLUSIONS: Among
      patients with ACS, the unrestricted use of EES is associated with improved
      clinical outcome compared with SES during long-term follow-up to 3 years.
      Notably, the risk of stent thrombosis was lower among EES-treated ACS patients.

PMID- 22361599
TI  - Functional assessment of jailed side branches in coronary bifurcation lesions
      using fractional flow reserve.
AB  - OBJECTIVES: This study was designed to assess the functional significance of side
      branches after stent implantation in main vessels using fractional flow reserve
      (FFR). BACKGROUND: Little is known about the functional significance of side
      branches after stent implantation in main vessels in coronary bifurcation
      lesions. METHODS: Between May 2007 and January 2011, 230 side branches in 230
      patients after stent implantation in main vessels were assessed by FFR and were
      consecutively enrolled. RESULTS: Median FFR at the side branch was 0.91
      (interquartile range: 0.85 to 0.95). There was a negative correlation between the
      diameter stenosis (DS) by quantitative coronary angiography (QCA) and FFR of side
      branch (r=-0.21, p=0.002), but only 41 (17.8%) side branches were functionally
      significant after stent implantation in the main vessel. Among 67 side branches
      with >50% DS by QCA, 19 (28.4%) had FFR<=0.80, and among 163 side branches with
      <=50% DS by QCA, 22 (13.5%) had FFR<=0.80 after stent implantation in main
      vessels. On the basis of receiver-operating characteristic curves, the optimal
      cutoff value of DS by QCA of the side branch was 54.9%, and the area under the
      curve was 0.64 (95% confidence interval [CI]: 0.58 to 0.71, p<0.001) with a 41.5%
      sensitivity, an 83.1% specificity, a 34.7% positive predictive value, an 86.3%
      negative predictive value, and a 75.7% accuracy. Multivariate binary logistic
      regression analysis identified DS by QCA (odds ratio [OR]: 1.04, 95% CI: 1.02 to
      1.06, p=0.001) and reference vessel diameter (OR: 0.28, 95% CI: 0.10 to 0.77,
      p=0.014) before stent implantation as independent predictors of the side branches
      with FFR<=0.80 after stent implantation. CONCLUSIONS: Most side branch lesions do
      not have functional significance after stent implantation in the main vessel, and
      quantitative coronary angiography is unreliable in assessing the functional
      severity of these lesions.

PMID- 22361600
TI  - No evidence of "obesity paradox" after treatment with drug-eluting stents in a
      routine clinical practice: results from the prospective multicenter German DES.DE
      (German Drug-Eluting Stent) Registry.
AB  - OBJECTIVES: The aim of this study was to compare clinical outcomes among
      unselected patients stratified in categories of body mass index, who underwent
      percutaneous coronary intervention (PCI) with either sirolimus-eluting or
      paclitaxel-eluting stents. BACKGROUND: Overweight and obesity are often
      considered risk factors for cardiovascular events. However, recent studies have
      associated obesity with better outcomes after PCI with bare-metal stents. Data
      from routine clinical practice using drug-eluting stents (DES) focusing on this
      "obesity paradox" are not available. METHODS: We used data from DES.DE (German
      Drug-Eluting Stent) registry to compare in-hospital and 1-year outcomes among
      unselected patients undergoing PCI with DES implantation. Primary endpoints were
      the rate of major adverse cardiac and cerebrovascular events (MACCE) (defined as
      the composite of death, myocardial infarction, and stroke) and target vessel
      revascularization (TVR). RESULTS: Between October 2005 and 2006, 1,436 normal
      weight, 2,839 overweight, and 1,531 obese patients treated with DES were enrolled
      at 98 sites. Baseline clinical parameters were more severe in overweight and
      obese patients; 1-year follow-up comparison between groups revealed similar rates
      of all-cause death (3.3% vs. 2.4% vs. 2.4%; p=0.17), MACCE (7.1% vs. 5.6% vs.
      5.5%; p=0.09), and TVR in survivors (10.9% vs. 11.7% vs. 11.6%; p=0.56) in normal
      weight individuals compared with overweight or obese patients. Such results
      persisted after risk-adjustment for heterogeneous baseline characteristics of
      groups and were independent of the types of DES. CONCLUSIONS: DES.DE revealed no
      evidence of "obesity paradox" in a routine clinical practice using DES.

PMID- 22361602
TI  - Myocardial circulation distal to chronic total occlusions: a brighter light at
      the end of the tunnel.

PMID- 22361601
TI  - Endothelial and smooth muscle cells dysfunction distal to recanalized chronic
      total coronary occlusions and the relationship with the collateral connection
      grade.
AB  - OBJECTIVES: This study sought to assess the vascular function in patients with
      chronic total coronary occlusions (CTO) immediately after successful percutaneous
      recanalization and its relation with the pre-existing collateral circulation.
      BACKGROUND: CTOs represent a long-acting occlusion of a coronary vessel, in which
      the progressively developed collateral circulation may limit ischemia and
      symptoms. However, it is unknown if the coronary segment distal to the occlusion
      has a preserved vascular function. METHODS: We prospectively enrolled 19
      consecutive patients, after percutaneous coronary intervention of a CTO. Luminal
      diameter, measured by quantitative coronary angiography, and coronary blood flow
      at level of epicardial coronary artery distal to the treated CTO was assessed
      before and after administration of acetylcholine (Ach), adenosine, and
      nitroglycerin (NTG). Collaterals were assessed angiographically by grading of
      Rentrop and of collateral connections (CC1: threadlike continuous connection;
      CC2: side branch-like connection). RESULTS: Overall, Ach and adenosine caused
      coronary artery vasoconstriction (p=0.001 and p=0.004, respectively), whereas NTG
      failed to induce vasodilation (p=0.084). Coronary blood flow significantly
      decreased with Ach (p=0.005), significantly increased with NTG (p=0.035), and did
      not change with adenosine (p=0.470). Patients with CC2 collaterals (n=8) had less
      vasoconstriction response and reduction in coronary blood flow after Ach (p=0.005
      and p=0.008, respectively), and better vasomotor response to NTG (p=0.029) than
      patients with CC1 collaterals (n=11). CONCLUSIONS: Significant endothelial and
      smooth muscle dysfunction is present in the distal segments of successfully
      recanalized CTOs, and that seems to be more pronounced in the presence of a low
      grading of collateral circulation.

PMID- 22361603
TI  - Protective effect of telmisartan against endothelial dysfunction after coronary
      drug-eluting stent implantation in hypertensive patients.
AB  - OBJECTIVES: The aim of this prospective, randomized study was to evaluate the
      effects of telmisartan, compared with the calcium-channel blocker amlodipine, on
      endothelial function after coronary drug-eluting stent (DES) implantation in
      hypertensive patients. BACKGROUND: DES implantation impairs local endothelial
      function, which may be associated with future cardiovascular events. Telmisartan,
      which has unique peroxisome proliferator-activated-receptor-gamma-mediated
      effects in addition to its renin-angiotensin system-inhibition effects, has
      favorable effects on endothelial function. METHODS: Fifty-one hypertensive
      patients with coronary artery stenosis but without coronary artery spasm, treated
      with a sirolimus-eluting stent, were randomly assigned to either the telmisartan
      (25 cases) or amlodipine (26 cases) treatment groups. At baseline and at 3 months
      after DES implantation, endothelium-dependent and -independent vasomotion were
      evaluated by quantitative coronary angiography under the condition of medication
      withdrawal. The mean luminal diameter of a 20-mm coronary segment, beginning 5 mm
      distal to the stent, was measured before and after infusion of intracoronary
      acetylcholine (10(-7), 10(-6) mol/l) and then again after infusion of
      nitroglycerin. RESULTS: Blood pressure was comparable between groups at baseline
      and after 3 months. Vasoconstriction after acetylcholine infusion at 3 months
      (impaired endothelial function) was less pronounced in the telmisartan group than
      in the amlodipine group (p<0.0001), although there was no significant difference
      between the 2 groups before DES implantation. The response to nitroglycerin did
      not differ between groups before or at 3 months after DES implantation.
      CONCLUSIONS: Telmisartan, compared with amlodipine, significantly ameliorated
      endothelial dysfunction after DES implantation in terms of vasoconstriction
      induced by acetylcholine.

PMID- 22361604
TI  - Timing of angiography with a routine invasive strategy and long-term outcomes in
      non-ST-segment elevation acute coronary syndrome: a collaborative analysis of
      individual patient data from the FRISC II (Fragmin and Fast Revascularization
      During Instability in Coronary Artery Disease), ICTUS (Invasive Versus
      Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention
      Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST
      Elevation Myocardial Infarction) Trials.
AB  - OBJECTIVES: This study sought to investigate long-term outcomes after early or
      delayed angiography in patients with non-ST-segment elevation acute coronary
      syndrome (nSTE-ACS) undergoing a routine invasive management. BACKGROUND: The
      optimal timing of angiography in patients with nSTE-ACS is currently a topic for
      debate. METHODS: Long-term follow-up after early (within 2 days) angiography
      versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II
      (Fragmin and Fast Revascularization During Instability in Coronary Artery
      Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary
      Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in
      Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR)
      nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or
      myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated
      with Cox regression models. Adjustments were made for the FIR risk score, study,
      and the propensity of receiving early angiography using inverse probability
      weighting. RESULTS: Of 2,721 patients originally randomized to the routine
      invasive arm, consisting of routine angiography and subsequent revascularization
      if suitable, 975 underwent early angiography and 1,141 delayed angiography. No
      difference was observed in 5-year cardiovascular death or myocardial infarction
      in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p=0.61) and
      adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p=0.54) Cox regression models.
      CONCLUSIONS: In the FIR database of patients presenting with nSTE-ACS, the timing
      of angiography was not related to long-term cardiovascular mortality or
      myocardial infarction. (Invasive Versus Conservative Treatment in Unstable
      Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative
      Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation
      Myocardial Infarction [the Third Randomised Intervention Treatment of Angina
      Trials (RITA-3)]; ISRCTN07752711).

PMID- 22361605
TI  - Procedural factors associated with percutaneous coronary intervention-related
      ischemic stroke.
AB  - OBJECTIVES: This study sought to determine whether procedural factors during
      percutaneous coronary intervention (PCI) are associated with the occurrence of
      ischemic stroke or transient ischemic attack (PCI-stroke). BACKGROUND: Stroke is
      a devastating complication of PCI. Demographic predictors are nonmodifiable.
      Whether PCI-stroke is associated with procedural factors, which may be
      modifiable, is unknown. METHODS: We performed a single-center retrospective study
      of 21,497 PCI hospitalizations between 1994 and 2008. We compared procedural
      factors from patients who suffered an ischemic stroke or transient ischemic
      attack related to PCI (n=79) and a control group (n=158), and matched them 2:1
      based on a predicted probability of stroke developed from a logistic regression
      model. RESULTS: PCI-stroke procedures involved the use of more catheters (median:
      3 [quarter (Q) 1, Q3: 3, 4] vs. 3 [Q1, Q3: 2, 3], p<0.001), greater contrast
      volumes (250 ml vs. 218 ml, p=0.006), and larger guide caliber (median: 7-F [Q1,
      Q3: 6, 8] vs. 6-F [Q1, Q3: 6, 8], p<0.001). The number of lesions attempted
      (1.7+/-0.8 vs. 1.5+/-0.8, p=0.14) and stents placed (1.4+/-1.2 vs. 1.2+/-1.1,
      p=0.35) were similar between groups, but PCI-stroke patients were more likely to
      have undergone rotational atherectomy (10% vs. 3%, p=0.029). Overall procedural
      success was lower in the PCI-stroke group compared with controls (71% vs. 85%,
      p=0.017). Evaluation of the entire PCI population revealed no difference in the
      rate of PCI-stroke between radial and femoral approaches (0.4% vs. 0.4%, p=0.78).
      CONCLUSIONS: Ischemic stroke related to PCI is associated with potentially
      modifiable technical parameters. Careful procedural planning is warranted,
      particularly in patients at increased risk.

PMID- 22361606
TI  - True percutaneous approach for transfemoral aortic valve implantation using the
      Prostar XL device: impact of learning curve on vascular complications.
AB  - OBJECTIVES: The purpose of this study was to evaluate the incidence of vascular
      complications and the predictors of Prostar failure for a "true percutaneous
      approach" in transfemoral transcatheter aortic valve implantation (TAVI).
      BACKGROUND: Safety and efficacy of a true percutaneous approach in transfemoral
      TAVI has not been described in a large prospective cohort. METHODS: Among 264
      patients included in our prospective TAVI database (October 2006 to December
      2010), transfemoral-TAVI was performed in 170 patients. True percutaneous
      approach was performed in 142 consecutive patients since March 2008. Successful
      closure with Prostar was defined as adequate hemostasis without Prostar-related
      vascular complications. We compared the incidence of vascular complications in
      our early and late experience. RESULTS: Patients were 83.0+/-7.2 years old and
      with a EuroSCORE of 24.0+/-11.6%. The Edwards valve (Edwards Lifesciences,
      Irvine, California) (18- to 24-F) was used in 109 cases and the CoreValve
      (Medtronic, Minneapolis, Minnesota) (18-F) in 31. The sheath outer diameter to
      minimal femoral diameter ratio (SFAR) was 0.96+/-0.14. Successful closure was
      achieved in 90.7%, and was significantly increased (95.7% vs. 85.7%, p=0.047) in
      the late experience group. Cross-over to surgery was required in 3.6%. Vascular
      complications occurred in 20.0%, and were significantly lower in the late
      experience group (11.4% vs. 28.6%, p=0.012). Major vascular complications (2.9%
      vs. 14.3%, p=0.018) were decreased in the late experience group. Early experience
      (hazard ratio [HR]: 3.66, 95% confidence interval [CI]: 1.04 to 13.89, p=0.047)
      and SFAR (HR: 110.80, 95% CI: 1.15 to 10,710.73, p=0.044) predicted Prostar
      failure by univariate analysis. CONCLUSIONS: Experience reduced major vascular
      complications in a true percutaneous approach for transfemoral-TAVI. Further
      application of this less invasive strategy is feasible and may be beneficial, in
      this high-risk patient cohort.

PMID- 22361608
TI  - Live case demonstration of interventional cardiology procedures: a regulatory
      perspective.

PMID- 22361607
TI  - Patient safety and outcomes from live case demonstrations of interventional
      cardiology procedures.
AB  - OBJECTIVES: The goal of this study was to examine the safety and results of
      interventional procedures performed during the broadcast of live case
      demonstrations. BACKGROUND: Professional meetings using live case demonstrations
      to present cutting-edge technology are considered a valuable educational
      resource. There is an ongoing discussion on whether patients who are treated
      during live case demonstrations are exposed to a higher risk. METHODS: Between
      1998 and 2010, 101 patients were treated during live transmissions from a single
      center in 15 invasive-cardiology conferences. Technical success was defined as
      the ability to effectively perform the planned procedure without any major
      complication. The primary endpoint of the study was the composite occurrence of
      death, myocardial infarction, or stroke. RESULTS: The interventional procedures
      included coronary (n=66), carotid (n=15), peripheral (n=1), valvular (n=2),
      congenital heart disease (n=12), and complex electrophysiological mapping and
      ablation interventions (n=7). In 4 cases, the intended procedure was not done.
      The procedure was technically successful in 95%. In 5 cases, the procedure was
      unsuccessful because of the inability to cross a chronic total occlusion. There
      were no deaths during the hospital stay, and the composite primary endpoint
      occurred in 2 patients: a minor stroke following an atrial fibrillation ablation
      and a rise in serum troponin levels after percutaneous coronary intervention.
      These results were no different from those of 66 matched controls who underwent
      procedures performed by the same operators but not as live case demonstrations
      (relative risk: 0.32; 95% confidence interval: 0.02 to 3.62, p=0.62).
      CONCLUSIONS: In this consecutive series of interventional cardiology procedures
      that were performed by expert operators during live demonstration courses, the
      procedural and 30-day clinical outcomes were similar to those found in daily
      practice and to those that have been reported in the contemporary published data.
      These results suggest that broadcasting live case demonstrations in selected
      patients from selected centers may be safe.

PMID- 22361609
TI  - Live case demonstration of interventional cardiology procedures: is it really
      safe?

PMID- 22361610
TI  - Late complication: Xience V stent fractures with restenosis.

PMID- 22361611
TI  - Transjugular balloon mitral valvotomy in a patient with inferior vena-caval
      interruption.

PMID- 22361612
TI  - Intracoronary adenosine administration in the right coronary artery: a word of
      caution.

PMID- 22361614
TI  - All the world's a stage.

PMID- 22361615
TI  - Acute stent thrombosis: technical complication or inadequate antithrombotic
      therapy? An optical coherence tomography study.

PMID- 22361616
TI  - Hierarchical organization from self-assembling disulfide macrocycles.
AB  - We report cystine-based macrocyclic compounds showing very unique self-assembling
      behavior. 24-membered disulfide macrocycle 3 shows a helical and tubular
      organization and also forms an insoluble plaque that is birefringent with congo
      red dye. 48-membered macrocycle 4 shows a vesicle-like assembly with capability
      for encapsulation, as demonstrated by rhodamine B encapsulation.

PMID- 22361617
TI  - Malin knockout mice support a primary role of autophagy in the pathogenesis of
      Lafora disease.
AB  - Lafora disease (LD), a fatal neurodegenerative disorder characterized by
      intracellular inclusions called Lafora bodies (LBs), is caused by recessive loss
      of-function mutations in the genes encoding either laforin or malin. Previous
      studies suggested a role of these proteins in regulating glycogen biosynthesis,
      in glycogen dephosphorylation and in the modulation of intracellular proteolytic
      systems. However, the contribution of each of these processes to LD pathogenesis
      is unclear. Here we review our recent finding that dysfunction of autophagy is a
      common feature of both laforin- and malin-deficient mice, preceding other
      pathological manifestations. We propose that autophagy plays a primary role in LD
      pathogenesis and is a potential target for its treatment.

PMID- 22361618
TI  - Mitophagy in cells with mtDNA mutations: being sick is not enough.
AB  - Despite the emergence of autophagy as a key process for mitochondrial quality
      control, the existence and persistence of pathogenic mtDNA mutations in human
      disease suggests that the degradation of dysfunctional mitochondria does not
      occur widely in vivo. During macroautophagy, a double-membraned cup-shaped
      structure engulfs cytosolic content. This autophagic vesicle then fuses with
      lysosomes, allowing hydrolytic enzymes to degrade the contents. Mitochondrial
      autophagy, or mitophagy, is thought to degrade damaged or nonfunctioning
      mitochondria specifically. The Parkinson disease-related proteins PINK1 (a
      mitochondrially localized kinase) and PARK2 (PARKIN, a cytosolically-localized E3
      ubiquitin ligase) are essential for targeting mitochondria for mitophagy. Upon
      chemical uncoupling of the mitochondrial transmembrane potential (Deltapsi(m)),
      PINK1 located in the mitochondrial outer membrane recruits PARK2 from the cytosol
      to the mitochondria, followed by delivery of the organelle to the autophagic
      machinery for degradation.

PMID- 22361621
TI  - The Charcot joint: a modern neurologic perspective.
AB  - The Charcot joint, or Charcot neuroarthropathy, is a syndrome that was described
      over 140 years ago but one with very little exposure in the neurologic
      literature. We present a case recently seen and then discuss the history,
      epidemiology, pathophysiology, clinical features, and diagnosis of acute and
      chronic Charcot joint disease with particular emphasis on the value and
      limitations of imaging. A diagnostic algorithm is proposed. We also review the
      therapeutic strategies available for acute and chronic Charcot joints with a
      treatment algorithm. This review is aimed at enhancing the awareness of
      neurologists regarding Charcot neuroarthropathy, because they are often the
      principal caregivers for patients with peripheral neuropathy. We hope to promote
      early detection of acute Charcot neuroarthropathy, thereby reducing or preventing
      the bony deformation of chronic Charcot neuroarthropathy.

PMID- 22361622
TI  - Neuromuscular diseases associated with chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a growing international health problem, and
      more than 170 million people are chronic carriers. Up to 50% of HCV-positive
      patients develop at least one extrahepatic manifestation during the course of
      disease. To varying degrees of certainty, there is evidence of an association
      between chronic HCV infection and a variety of neuromuscular diseases. The
      pathogenesis of most extrahepatic diseases remains unclear but possibly includes
      HCV lymphotropism and/or HCV-induced autoantibodies. The therapeutic approach to
      HCV-associated autoimmune disorders entails eradication of HCV with one of the
      recombinant interferon-alpha preparations with or without additional
      immunosuppressive drugs.

PMID- 22361619
TI  - Methylthioninium chloride (methylene blue) induces autophagy and attenuates
      tauopathy in vitro and in vivo.
AB  - More than 30 neurodegenerative diseases including Alzheimer disease (AD),
      frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are
      characterized by the accumulation of an aggregated form of the microtubule
      binding protein tau in neurites and as intracellular lesions called
      neurofibrillary tangles. Diseases with abnormal tau as part of the pathology are
      collectively known as the tauopathies. Methylthioninium chloride, also known as
      methylene blue (MB), has been shown to reduce tau levels in vitro and in vivo and
      several different mechanisms of action have been proposed. Herein we demonstrate
      that autophagy is a novel mechanism by which MB can reduce tau levels. Incubation
      with nanomolar concentrations of MB was sufficient to significantly reduce levels
      of tau both in organotypic brain slice cultures from a mouse model of FTD, and in
      cell models. Concomitantly, MB treatment altered the levels of LC3-II, cathepsin
      D, BECN1, and p62 suggesting that it was a potent inducer of autophagy. Further
      analysis of the signaling pathways induced by MB suggested a mode of action
      similar to rapamycin. Results were recapitulated in a transgenic mouse model of
      tauopathy administered MB orally at three different doses for two weeks. These
      data support the use of this drug as a therapeutic agent in neurodegenerative
      diseases.

PMID- 22361623
TI  - Neuromuscular disorders associated with hepatitis B virus infection.
AB  - Approximately 400 million worldwide are chronically infected with the hepatitis B
      virus (HBV). During the course of illness, approximately 20% of patients develop
      disease manifestations outside the liver. Neuropathy develops in approximately 5%
      of patients with chronic HBV infection and rarely during acute HBV infection. The
      pathogenesis of the various HBV-associated neuropathy syndromes possibly involves
      deposition of immune complexes in nerves or blood vessel walls. Direct viral
      infection of nerves has not been demonstrated. Management entailed supportive
      care with antiviral and immunomodulatory treatment as clinically indicated. Rare
      cases of muscle disease, mostly inflammatory myopathy, have been associated with
      HBV infection. Presumably, HBV-associated antigens trigger immune mechanisms
      directed against components of muscle tissue. There is no evidence of replicative
      virus infection of muscle fibers. Management entailed immunomodulatory treatment,
      occasionally with anti-HBV therapy. Physicians should be aware that HBV infection
      has the potential to trigger presumed immune-mediated neuromuscular syndromes.

PMID- 22361624
TI  - Effect of demyelinating ulnar nerve injury on strength and fatigue.
AB  - OBJECTIVES: Conduction block (CB) from focal neuropathy is often associated with
      weakness and fatigue in affected muscles. Ulnar neuropathy at the elbow (UNE)
      provides an excellent model to examine the relationships between
      electrophysiologically defined CB and quantitative measurement of weakness and
      fatigue. METHODS: Eight healthy control subjects (47 +/- 14 years) and nine
      patients (53 +/- 3 years) with clinical and electrophysiological features of UNE
      with CB were studied. All underwent bilateral, ulnar motor nerve conduction
      studies recording from the first dorsal interosseous muscle as well as
      quantitative measurement of strength and fatigue of the first dorsal interosseous
      with a custom dynamometer. RESULTS: Strength and fatigue were similar in the
      dominant and nondominant hands of control subjects and unaffected limb in
      patients. Varying degrees of conduction block (14-62%, mean 36%) and conduction
      slowing (31 m/s +/- 7) were observed in those with UNE. CB was associated with
      significant reductions in strength (42%) and fatigue (23%) on a timed fatigue
      task. The reductions in strength (r = 0.74) and fatigue (r = 0.60) were strongly
      correlated with the degree of CB. CONCLUSIONS: CB in UNE defined by
      electrophysiological criteria was strongly correlated with weakness and fatigue
      in the first dorsal interosseous. Fatigue may be simply related to the reduction
      in strength, but activity or frequency dependent CB may also contribute.

PMID- 22361625
TI  - Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical
      features and therapeutic response.
AB  - OBJECTIVE: The frequency of ocular myasthenia gravis (OMG) in patients referred
      to an academic neuro-ophthalmology clinic for suspected myasthenia gravis is not
      known. Our objective was to determine the frequency of ocular OMG in patients
      referred to an academic neuro-ophthalmologist and determine alternate diagnoses
      and response to therapy. METHODS: We performed a retrospective chart review of
      patients presenting to the University of Kansas Neuro-Ophthalmology Clinic with
      suspected OMG over 9 years. We defined OMG as isolated ptosis/diplopia at initial
      presentation supported by at least one of the following abnormal tests:
      edrophonium test, ice test, Cogan lid twitch, fatigability on sustained upgaze,
      acetylcholine receptor binding antibody, greater than 10% decrement on repetitive
      stimulation, or abnormal single-fiber jitter. We also determined the cause of
      ptosis/diplopia if it was not the result of OMG. Patients who progressed from OMG
      to generalized disease were termed transformed myasthenia gravis (TMG). RESULTS:
      One hundred thirty-eight patients were referred with mean age at presentation 58
      +/- 19 years. Myasthenia gravis was diagnosed in 101 patients; 95 had OMG; six
      had generalized MG. Diagnosis in the other 37 was cranial nerve palsies (nine),
      levator dehiscence (five), multiple sclerosis (two), blepharospasm (two),
      decompensated phorias (three), accommodation spasm (four), exophoria (three),
      skew deviation (two), Graves disease (one), hypertropia (one), myopathy (one),
      neurosarcoidosis (one), progressive supranuclear palsy (one), Miller Fisher
      variant of Guillain-Barre syndrome (one), and obstructive sleep apnea (one). Mean
      follow-up was 3.0 +/- 2.8 years. Test sensitivity/specificity in OMG was
      fatigability on sustained upgaze 0.80/0.63; ice pack 0.80/0.25; Cogan lid twitch
      0.59/1.00; edrophonium 0.88/0.50; acetylcholine receptor binding antibody
      0.38/1.00; repetitive nerve stimulation 0.24/1.00; and single-fiber
      electromyography 0.90/1.00. Pyridostigmine was used without prednisone in 59 of
      97 patients with OMG and 12 of 59 developed TMG. Prednisone was used in 38
      patients; 21 of 38 (55%) met Myasthenia Gravis Foundation of America improvement
      status and none had TMG. CONCLUSION: The diagnosis of myasthenia gravis was
      confirmed in the majority of patients referred to our academic neuro
      ophthalmology clinic, but 27% did not have myasthenia gravis. It is possible that
      prednisone treatment of OMG may prevent progression to TMG, but further study is
      required.

PMID- 22361626
TI  - Shoulder pain in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To determine the frequency of shoulder pain in our amyotrophic lateral
      sclerosis (ALS) population and to explore potential associations with demographic
      and clinical features. METHODS: We retrospectively reviewed the medical records
      of 193 patients with ALS patients seen at the Lahey Clinic between 2005 and 2009.
      Patients were categorized by the predominance of upper and lower motor neuron
      signs and the body regions initially involved. The frequency of shoulder pain was
      identified in each of these subgroups. RESULTS: Forty-five (23%) of the 193
      patients reported shoulder pain at some time during the course of their illness.
      Age, gender, manual labor, prior shoulder problems, ALS phenotype, and initial
      region of involvement were not correlated with shoulder pain. Patients with
      shoulder pain were more likely to develop proximal arm weakness during their
      illness and to report pain elsewhere. CONCLUSIONS: Despite the limitations posed
      by this retrospective study, it underscores the prevalence of shoulder pain in
      patients with ALS. Further studies to identify risk factors, mechanisms of, and
      treatments for shoulder pain in patients with ALS may benefit this population.

PMID- 22361627
TI  - Loss of taste as the only cranial nerve finding in Guillain-Barre syndrome.

PMID- 22361629
TI  - Deposition and transport of functionalized carbon nanotubes in water-saturated
      sand columns.
AB  - Knowledge of the fate and transport of functionalized carbon nanotubes (CNTs) in
      porous media is crucial to understand their environmental impacts. In this study,
      laboratory column and modeling experiments were conducted to mechanistically
      compare the retention and transport of two types of functionalized CNTs (i.e.,
      single-walled nanotubes and multi-walled nanotubes) in acid-cleaned, baked, and
      natural sand under unfavorable conditions. The CNTs were highly mobile in the
      acid-cleaned sand columns but showed little transport in the both natural and
      baked sand columns. In addition, the retention of the CNTs in the both baked and
      natural sand was strong and almost irreversible even after reverse, high
      velocity, or surfactant flow flushing. Both experimental and modeling results
      showed that pH is one of the factors dominating CNT retention and transport in
      natural and baked sand. Retention of the functionalized CNTs in the natural and
      baked sand columns reduced dramatically when the system pH increased. Our results
      suggest that the retention and transport of the functionalized CNTs in natural
      sand porous media were mainly controlled by strong surface deposition through the
      electrostatic and/or hydrogen-bonding attractions between surface function groups
      of the CNTs and metal oxyhydroxide impurities on the sand surfaces.

PMID- 22361630
TI  - Optimization of cultural conditions for growth associated chromate reduction by
      Arthrobacter sp. SUK 1201 isolated from chromite mine overburden.
AB  - Arthrobacter sp. SUK 1201, a chromium resistant and reducing bacterium having 99%
      sequence homology of 16S rDNA with Arthrobacter sp. GZK-1 was isolated from
      chromite mine overburden dumps of Orissa, India. The objective of the present
      study was to optimize the cultural conditions for chromate reduction by
      Arthrobacter sp. SUK 1201. The strain showed 67% reduction of 2mM chromate in 7
      days and was associated with the formation of green insoluble precipitate, which
      showed characteristic peak of chromium in to energy dispersive X-ray analysis.
      However, Fourier transform infrared spectra have failed to detect any
      complexation of end products of Cr(VI) reduction with the cell mass. Reduction of
      chromate increased with increased cell density and was maximum at 10(10)cells/ml,
      but the reduction potential decreased with increase in Cr(VI) concentration.
      Chromate reducing efficiency was promoted when glycerol and glucose was used as
      electron donors. Optimum pH and temperature of Cr(VI) reduction was 7.0 and 35 
      degrees C respectively. The reduction process was inhibited by several metal ions
      and metabolic inhibitors but not by Cu(II) and DNP. These findings suggest that
      Arthrobacter sp. SUK 1201 has great promise for use in Cr(VI) detoxification
      under a wide range of environmental conditions.

PMID- 22361631
TI  - Phenformin as prophylaxis and therapy in breast cancer xenografts.
AB  - BACKGROUND: Observations that diabetics treated with biguanide drugs have a
      reduced risk of developing cancer have prompted an enthusiasm for these agents as
      anti-cancer therapies. We sought to determine the efficacy of the biguanide
      phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor
      (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in
      immunocompromised mice. We also compared the efficacy of phenformin and metformin
      in the treatment of MDAMB231. METHODS: Immunocompromised mice were divided into
      groups: (1) phenformin administered for 2 weeks prior to cell injection; (2)
      established tumours treated with phenformin; (3) established tumours treated with
      metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment
      tumours, liver and spleen were harvested for further analysis. RESULTS:
      Phenformin significantly inhibited both the development and growth of MCF7 and
      MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without
      murine toxicity. The number of mitotic figures was significantly fewer in
      xenografts treated with phenformin compared with controls. Results suggested that
      the mechanism of action of phenformin in vivo is consistent with AMPK activation.
      CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and
      should be considered for clinical trials both in ER-positive and triple-negative
      breast cancer.

PMID- 22361632
TI  - Prognostic value of a cell cycle progression signature for prostate cancer death
      in a conservatively managed needle biopsy cohort.
AB  - BACKGROUND: The natural history of prostate cancer is highly variable and it is
      difficult to predict. We showed previously that a cell cycle progression (CCP)
      score was a robust predictor of outcome in a conservatively managed cohort
      diagnosed by transurethral resection of the prostate. A greater need is to
      predict outcome in patients diagnosed by needle biopsy. METHODS: Total RNA was
      extracted from paraffin specimens. A CCP score was calculated from expression
      levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason
      score, baseline prostate-specific antigen level, age, clinical stage, and extent
      of disease. The primary endpoint was death from prostate cancer. RESULTS: In
      univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer
      was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score.
      The CCP score was only weakly correlated with standard prognostic factors and in
      a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95%
      CI (1.31, 2.09), P=3 * 10(-5)), with Gleason score (P=5 * 10(-4)) and prostate
      specific antigen (PSA) (P=0.017) providing significant additional contributions.
      CONCLUSION: For conservatively managed patients, the CCP score is the strongest
      independent predictor of cancer death outcome yet described and may prove
      valuable in managing clinically localised prostate cancer.

PMID- 22361633
TI  - Hedgehog pathway activation in human transitional cell carcinoma of the bladder.
AB  - BACKGROUND: The Hedgehog (Hh) signalling pathway functions as an organiser in
      embryonic development. Recent studies have shown constitutive activation of this
      pathway in various malignancies, but its role in bladder cancer remains poorly
      studied. METHODS: Expression levels of 31 genes and 9 microRNAs (miRNAs) involved
      in the Hh pathway were determined by quantitative real-time RT-PCR in 71 bladder
      tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC)
      bladder cancers), as well as in 6 bladder cancer cell lines. RESULTS: The SHH
      ligand gene and Gli-inducible target genes (FOXM1, IGF2, OSF2, H19, and SPP1)
      were overexpressed in tumour samples as compared with normal bladder tissue. SHH
      overexpression was found in 96% of NMIBC and 52% of MIBC samples, as well as in
      two bladder cancer cell lines. Altered expression of miRNAs supported their
      oncogene or tumour-suppressor gene status. In univariate analysis, high
      expression levels of PTCH2, miRNA-92A, miRNA-19A, and miRNA-20A were associated
      with poorer overall survival in MIBC (P=0.02, P=0.012, P=0.047, and P=0.036,
      respectively). CONCLUSION: We observed constitutive activation of the Hh pathway
      in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes
      and miRNAs involved in the Hh pathway may have prognostic value at the individual
      level.

PMID- 22361634
TI  - HER2/neu and Ki-67 expression predict non-invasive recurrence following breast
      conserving therapy for ductal carcinoma in situ.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast
      cancer that may progress to invasive cancer. Identification of factors that
      predict recurrence and distinguish DCIS from invasive recurrence would facilitate
      treatment recommendations. We examined the prognostic value of nine molecular
      markers on the risks of local recurrence (DCIS and invasive) among women treated
      with breast-conserving therapy. METHODS: A total of 213 women who were treated
      with breast-conserving therapy between 1982 and 2000 were included; 141 received
      breast-conserving surgery alone and 72 cases received radiotherapy. We performed
      immunohistochemical staining on the DCIS specimen for nine markers: oestrogen
      receptor, progesterone receptor, Ki-67, p53, p21, cyclinD1, HER2/neu, calgranulin
      and psoriasin. We performed univariable and multivariable survival analyses to
      identify markers associated with the recurrence. RESULTS: The rate of recurrence
      at 10 years was 36% for patients treated with breast-conserving surgery alone and
      18% for women who received breast-conserving surgery and radiotherapy.
      HER2/neu+/Ki-67+ expression was associated with an increased risk of DCIS
      recurrence, independent of grade and age (HR=3.22; 95% CI: 1.47-7.03; P=0.003).
      None of the nine markers were predictive of invasive recurrence. CONCLUSION:
      Women with a HER2/neu/neu+/Ki67+ DCIS have a higher risk of developing DCIS local
      recurrence after breast-conserving surgery.

PMID- 22361635
TI  - "This is our sanctuary": perceptions of safety among exotic dancers in Baltimore,
      Maryland.
AB  - Occupational safety researchers have increasingly recognized the important
      influence of social and structural factors on safety perception and behaviors in
      occupational settings. This qualitative study was conducted to explore the nature
      of the safety climate of exotic dance clubs in Baltimore, Maryland and the
      mechanisms through which this sexual geography informs dancers' perceptions of
      safety and experience of sex work. Structured observations and semi-structured
      qualitative interviews (N=40) were conducted with club dancers, doormen,
      managers, and bartenders from May through August, 2009. Data were analyzed using
      an inductive approach whereby themes emerged from the data itself. Atlas-ti was
      used for data analysis. Perceptions of safety within exotic dance clubs were born
      from an interplay between the physical, social, and symbolic environments. These
      perceptions were closely tied to dancers' construction of sex work inside versus
      outside the club. Understanding the contextual factors, which influence how
      dancers understand and prioritize risk in their work settings, is crucial for
      creating policies and programs, which effectively reduce risk in this
      environment.

PMID- 22361636
TI  - The characteristics of mobile families with young children in England and the
      impact of their moves on neighbourhood inequalities in maternal and child health.
AB  - This study compares the health and socio-demographic characteristics of
      residentially mobile families with young children in England to families that do
      not move and assesses the impact of their moves upon inequalities in health
      between neighbourhoods. The analysis uses data from the first two waves of the
      Millennium Cohort Study describing 9022 cohort members, born in 2000-2002, and
      their families. A third of the families moved between the waves of the survey
      when the children were aged nine months and three years. Mobile families moved
      disproportionately toward less deprived areas but had disadvantaged socio
      economic characteristics and poor outcomes for infant's birth weight and
      accidents and mother's self-rated health, limiting longstanding illness and
      mental health. Health outcomes were worst among the minority moving to more
      deprived neighbourhoods. Families' moves moderately increased health inequalities
      between neighbourhoods with high and low deprivation.

PMID- 22361637
TI  - [Adherence to a population-based colorectal cancer screening program in Catalonia
      (Spain), 2000-2008].
AB  - OBJECTIVE: To analyze correlates of adherence to colorectal cancer screening with
      biennial fecal occult blood testing in asymptomatic individuals aged 50 to 69
      years. METHODS: A cross-sectional telephone survey was conducted among people (n
      = 1,193) invited to participate in at least two successive rounds of a population
      based colorectal cancer screening program in L'Hospitalet de Llobregat
      (Barcelona, Spain). Subjects were classified according to their adherence to
      colorectal cancer screening guidelines (non-adherent, irregular adherent and
      totally adherent). Independent variables were sociodemographic variables, self
      perceived health, attitudes and beliefs regarding colorectal cancer and
      preventive activities. Binary and politomous logistic regression models were
      performed. RESULTS: Of the individuals invited to participate in the screening
      program, 14.4% were adherent to screening recommendations and 18.4% were
      occasionally adherent. Significant differences were found in beliefs and
      attitudes regarding colorectal cancer and its early detection among adherent and
      non-adherent individuals. Sharing the decision to participate in screening with a
      family member increased adherence by nine- and tweve-fold. A positive perception
      of the screening process was a facilitator to adherence. CONCLUSIONS: Attitudes
      and beliefs regarding colorectal cancer and its early detection, as well as
      familial support, are associated with initial participation in colorectal cancer
      screening but do not affect the persistence of preventive behavior over time.

PMID- 22361638
TI  - [The illicit drug market].

PMID- 22361639
TI  - [The Spanish version of the International Standard Classification of Occupations
      88: discrepancies in the number of rubrics].

PMID- 22361640
TI  - [Pharmaceutical expenditure among primary care physicians in the health area of
      Cuenca (Spain). Response].

PMID- 22361641
TI  - [Response rates in three opinion surveys performed through online questionnaires
      in the health setting].
AB  - The main advantages of online questionnaires are the speed of data collection and
      cost savings, but response rates are usually low. This study analyzed response
      rates and associated factors among health professionals in three opinion surveys
      in the autonomous region of Madrid. The participants, length of the questionnaire
      and topic differed among the three surveys. The surveys were conducted by using
      paid Internet software. The institutional e-mail addresses of distinct groups of
      health professionals were used. Response rates were highest in hospitals (up to
      63%) and administrative services and were lowest in primary care (less than 33%).
      The differences in response rates were analyzed in primary care professionals
      according to age, sex and professional category and only the association with age
      was statistically significant. None of the surveys achieved a response rate of
      60%. Differences were observed according to workplace, patterns of Internet
      usage, and interest in the subject.

PMID- 22361642
TI  - [A critical analysis of physical activity recommendations in Spain].
AB  - OBJECTIVE: To identify official documents with recommendations on physical
      activity published by the autonomous regions of Spain with the goal of evaluating
      their compliance with the physical activity recommendations of the World Health
      Organization (WHO). METHODS: We conducted a content analysis of 55 documents of
      the ministries of health of several regional governments containing
      recommendations on physical activity. RESULTS: Eighty-four percent of the
      autonomous regions in Spain made recommendations on aerobic physical activity and
      37% made recommendations on strength training. However, the number of documents
      consistent with the WHO criteria was as follows: aerobic activity (n=11, 58%),
      adults (n=10, 53%), the elderly (n=5, 26%), children/adolescents (n=1, 5%);
      strength training, adults (n=6, 32%), the elderly (n=3, 16%),
      children/adolescents (n=1, 5%); balance (n=5, 26%); at least 10minutes continuous
      physical activity (n=6, 32%); recommendation of up to 300minutes per week (n=10,
      53%); intensity of physical activity (n=2, 11%). CONCLUSIONS: The recommendations
      of the autonomous regions tend to focus on aerobic physical activity and to under
      represent strength training. Moreover, only one autonomous region conforms to the
      WHO recommendations for physical activity. The regions with higher rates of
      population aging and a higher percentage of children and adolescents fail to make
      recommendations on physical activity consistent with the WHO guidelines.

PMID- 22361643
TI  - [Use of Spanish proposals for measuring social class in health sciences].
AB  - OBJECTIVE: Recognizing the need for a consensus tool to measure social class in
      health sciences, in 1995 the Spanish Society of Epidemiology (Sociedad Espanola
      de Epidemiologia [SEE]) made a proposal for such a measure. The aim of this
      article was to explore the bibliometric impact of the SEE's proposal. METHODS:
      Articles citing the SEE's report and those citing articles published as a result
      of the report were identified using Google Scholar and Scopus. The information
      extracted from these articles consisted of year, nationality and impact factor of
      the journal, self-citation, information source, subject area, city of the first
      author, type of publication, study design, use of social class as a variable,
      number of social class categories, and the use of education or occupation to
      determine social class. RESULTS: The number of citations progressively increased.
      Citations also showed heterogeneity in the subject. Generally, citations were
      found in original articles and articles with a cross sectional design, were
      published in journals with impact factor and were by researchers working in
      Barcelona or Madrid. CONCLUSIONS: The SEE's proposal has proved to be an
      increasingly useful tool, applicable in different contexts. As suggested by the
      SEE, this proposal may need to be updated.

PMID- 22361645
TI  - [In defense of Gaceta Sanitaria].

PMID- 22361646
TI  - The current state of GMO governance: are we ready for GM animals?
AB  - Given the history of GMO conflict and debate, the GM animal future is dependent
      on the response of the regulatory landscape and its associated range of interest
      groups at national, regional and international levels. Focusing on the EU and the
      USA, this article examines the likely form of that multi-level response, the
      increased role of cultural values, the contribution of new and existing interest
      groups and the consequent implications for the commercialization of both green
      and red GM animal biotechnology.

PMID- 22361647
TI  - Production cost of a real microalgae production plant and strategies to reduce
      it.
AB  - The cost analysis of a real facility for the production of high value microalgae
      biomass is presented. The facility is based on ten 3 m3 tubular photobioreactors
      operated in continuous mode for 2 years, data of Scenedesmus almeriensis
      productivity but also of nutrients and power consumption from this facility being
      used. The yield of the facility was close to maximum expected for the location of
      Almeria, the annual production capacity being 3.8 t/year (90 t/ha.year) and the
      photosynthetic efficiency being 3.6%. The production cost was 69 ?/kg. Economic
      analysis shows that labor and depreciation are the major factors contributing to
      this cost. Simplification of the technology and scale-up to a production capacity
      of 200 t/year allows to reduce the production cost up to 12.6 ?/kg. Moreover, to
      reduce the microalgae production cost to approaches the energy or commodities
      markets it is necessary to reduce the photobioreactor cost (by simplifying its
      design or materials used), use waste water and flue gases, and reduce the power
      consumption and labor required for the production step. It can be concluded that
      although it has been reported that production of biofuels from microalgae is
      relatively close to being economically feasible, data here reported demonstrated
      that to achieve it by using the current production technologies, it is necessary
      to substantially reduce their costs and to operate them near their optimum
      values.

PMID- 22361648
TI  - Sustainable sanitation technology options for urban slums.
AB  - Poor sanitation in urban slums results in increased prevalence of diseases and
      pollution of the environment. Excreta, grey water and solid wastes are the major
      contributors to the pollution load into the slum environment and pose a risk to
      public health. The high rates of urbanization and population growth, poor
      accessibility and lack of legal status in urban slums make it difficult to
      improve their level of sanitation. New approaches may help to achieve the
      sanitation target of the Millennium Development Goal (MDG) 7; ensuring
      environmental sustainability. This paper reviews the characteristics of waste
      streams and the potential treatment processes and technologies that can be
      adopted and applied in urban slums in a sustainable way. Resource recovery
      oriented technologies minimise health risks and negative environmental impacts.
      In particular, there has been increasing recognition of the potential of
      anaerobic co-digestion for treatment of excreta and organic solid waste for
      energy recovery as an alternative to composting. Soil and sand filters have also
      been found suitable for removal of organic matter, pathogens, nutrients and micro
      pollutants from grey water.

PMID- 22361649
TI  - Is it necessary to close the peritoneum over the deep inguinal ring during
      laparoscopic orchidopexy?
AB  - BACKGROUND: During laparoscopic orchidopexy, some authors routinely close the
      peritoneum over the area of the deep inguinal ring (DIR). We report our
      experience, to determine whether leaving the peritoneum over the DIR without
      closure is associated with an increase in the occurrence of postoperative
      inguinal hernia. PATIENTS & METHODS: This is a retrospective review of patients
      who underwent laparoscopy for impalpable testes in 2004-2010. The patients were
      divided into two groups: I) cases in whom the peritoneum over the DIR was
      routinely closed, and II) cases in whom the DIR was left without closure. The
      patients were followed up in the outpatient clinic. RESULTS: During the study
      period, 442 boys underwent laparoscopy for 570 impalpable testes. The testis was
      found to be 'vanishing' or 'atrophic' in 182 (32%). The mobilized testis passed
      through the anatomical DIR in 198 (51%), and through a new deep ring in 190
      (49%). The DIR was closed (I) in 178 (46%) and left open (II) in 210 (54%) cases.
      On follow up (mean 50 months for I and 41 months for II), there were no cases of
      inguinal hernia. CONCLUSION: Closing the peritoneum over the area of the DIR may
      not be necessary, even in cases where the testis has to be passed through a
      medially created new deep ring, because of a short cord.

PMID- 22361650
TI  - Autophagy proteins play cytoprotective and cytocidal roles in leucine starvation
      induced cell death in Saccharomyces cerevisiae.
AB  - Autophagy is essential for prolonging yeast survival during nutrient deprivation;
      however, this report shows that some autophagy proteins may also be accelerating
      population death in those conditions. While leucine starvation caused YCA1
      mediated apoptosis characterized by increased annexin V staining, nitrogen
      deprivation triggered necrotic death characterized by increased propidium iodide
      uptake. Although a Deltaatg8 strain died faster than its parental strain during
      nitrogen starvation, this mutant died slower than its parent during leucine
      starvation. Conversely, a Deltaatg11 strain died slower than its parent during
      nitrogen starvation, but faster during leucine starvation. Curiously, although
      GFP-Atg8 complemented the Deltaatg8 mutation, this protein made ATG8 cells more
      sensitive to nitrogen starvation, and less sensitive to leucine starvation. These
      results were difficult to explain if autophagy only extended life but could be an
      indication that a second form of autophagy could concurrently facilitate either
      apoptotic or necrotic cell death.

PMID- 22361651
TI  - A novel interstitial deletion of 10q24.2q24.32 in a patient with renal coloboma
      syndrome.
AB  - Renal coloboma syndrome (RCS) is considered to be a rare autosomal dominant
      inherited disorder characterized by renal malformations and optic disc coloboma.
      Ocular anomalies range from asymptomatic abnormalities in retinal blood vessel
      patterning to large excavations of the optic nerve associated with reduced visual
      acuity. Commonly observed manifestations of the kidney are renal hypoplasia and
      vesicoureteric reflux leading to end-stage renal disease. Mutations in the PAX2
      gene on chromosome 10 have been identified in patients with RCS. Up to date,
      nucleotide substitutions, insertions, small deletions, one de novo translocation,
      and one 240 kb deletion of the coding region of the PAX2 gene have been described
      to be responsible for RCS. We report here a new case of a patient with RCS due to
      a deletion of 3.8 Mb on chromosome 10q. Deletions on the long arm of chromosome
      10 harboring the PAX2 gene seem to be a rare cause for RCS. Nevertheless, array
      CGH testing should represent an important and valuable addition to PAX2 gene
      sequencing in diagnostic of RCS.

PMID- 22361652
TI  - A thermally robust amine-imine nickel catalyst precursor for living
      polymerization of ethylene above room temperature.
AB  - A bulky amine-imine nickel complex containing two 2,6-diisopropyl substituents
      after activation with MMAO or Et(2)AlCl can polymerize ethylene in a living
      fashion over a period of 120 minutes at room temperature or above.

PMID- 22361653
TI  - Computational analysis of contractility in engineered heart tissue.
AB  - Engineered heart tissue (EHT) is a potential therapy for heart failure and the
      basis of functional in vitro assays of novel cardiovascular treatments. Self
      organizing EHT can be generated in fiber form, which makes the assessment of
      contractile function convenient with a force transducer. Contractile function is
      a key parameter of EHT performance. Analysis of EHT force data is often performed
      manually; however, this approach is time consuming, incomplete and subjective.
      Therefore, the purpose of this study was to develop a computer algorithm to
      efficiently and objectively analyze EHT force data. This algorithm incorporates
      data filtering, individual contraction detection and validation,
      inter/intracontractile analysis and intersample analysis. We found the algorithm
      to be accurate in contraction detection, validation and magnitude measurement as
      compared to human operators. The algorithm was efficient in processing hundreds
      of data acquisitions and was able to determine force-length curves, force
      frequency relationships and compare various contractile parameters such as peak
      systolic force generation. We conclude that this computer algorithm is a key
      adjunct to the objective and efficient assessment of EHT contractile function.

PMID- 22361654
TI  - A colon video analysis framework for polyp detection.
AB  - This paper presents an automated video analysis framework for the detection of
      colonic polyps in optical colonoscopy. Our proposed framework departs from
      previous methods in that we include spatial frame-based analysis and temporal
      video analysis using time-course image sequences. We also provide a video quality
      assessment scheme including two measures of frame quality. We extract colon
      specific anatomical features from different image regions using a windowing
      approach for intraframe spatial analysis. Anatomical features are described using
      an eigentissue model. We apply a conditional random field to model interframe
      dependences in tissue types and handle variations in imaging conditions and
      modalities. We validate our method by comparing our polyp detection results to
      colonoscopy reports from physicians. Our method displays promising preliminary
      results and shows strong invariance when applied to both white light and narrow
      band video. Our proposed video analysis system can provide objective diagnostic
      support to physicians by locating polyps during colon cancer screening exams.
      Furthermore, our system can be used as a cost-effective video annotation solution
      for the large backlog of existing colonoscopy videos.

PMID- 22361655
TI  - Image reconstruction using interval simulated annealing in electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is an imaging technique that attempts to
      reconstruct the impedance distribution inside an object from the impedance
      between electrodes placed on the object surface. The EIT reconstruction problem
      can be approached as a nonlinear nonconvex optimization problem in which one
      tries to maximize the matching between a simulated impedance problem and the
      observed data. This nonlinear optimization problem is often ill-posed, and not
      very suited to methods that evaluate derivatives of the objective function. It
      may be approached by simulated annealing (SA), but at a large computational cost
      due to the expensive evaluation process of the objective function, which involves
      a full simulation of the impedance problem at each iteration. A variation of SA
      is proposed in which the objective function is evaluated only partially, while
      ensuring boundaries on the behavior of the modified algorithm.

PMID- 22361656
TI  - Model-based seizure detection for intracranial EEG recordings.
AB  - This paper presents a novel model-based patient-specific method for automatic
      detection of seizures in the intracranial EEG recordings. The proposed method
      overcomes the complexities in the practical implementation of the patient
      specific approach of seizure detection. The method builds a seizure model (set of
      basis functions) for a priori known seizure (the template seizure pattern), and
      uses the statistically optimal null filters as a building block for the detection
      of similar seizures. The process of modeling the template seizure is fully
      automatic. Overall, the detection method involves the segmentation of the
      template seizure pattern, rejection of the redundant and noisy segments,
      extraction of features from the segments to generate a set of models, selection
      of the best seizure model, and training of the classifier. The trained classifier
      is used to detect similar seizures in the remaining data. The resulting seizure
      detection method was evaluated on a total of 304 h of single-channel depth EEG
      recordings from 14 patients. The system performance is further compared to the Qu
      Gotman patient-specific system using the same data. A significant improvement in
      the proposed system, in terms of specificity, is observed over the compared
      method.

PMID- 22361657
TI  - 2-D-3-D frequency registration using a low-dose radiographic system for knee
      motion estimation.
AB  - In this paper, a new method is presented to study the feasibility of the pose and
      the position estimation of bone structures using a low-dose radiographic system,
      the entrepreneurial operating system (designed by EOS-Imaging Company). This
      method is based on a 2-D-3-D registration of EOS bi-planar X-ray images with an
      EOS 3-D reconstruction. This technique is relevant to such an application thanks
      to the EOS ability to simultaneously make acquisitions of frontal and sagittal
      radiographs, and also to produce a 3-D surface reconstruction with its attached
      software. In this paper, the pose and position of a bone in radiographs is
      estimated through the link between 3-D and 2-D data. This relationship is
      established in the frequency domain using the Fourier central slice theorem. To
      estimate the pose and position of the bone, we define a distance between the 3-D
      data and the radiographs, and use an iterative optimization approach to converge
      toward the best estimation. In this paper, we give the mathematical details of
      the method. We also show the experimental protocol and the results, which
      validate our approach.

PMID- 22361658
TI  - Identification, characterization and quantification of a new impurity in
      deferasirox active pharmaceutical ingredient by LC-ESI-QT/MS/MS.
AB  - An unknown impurity was detected in deferasirox drug substance by a newly
      developed high performance liquid chromatography (HPLC) method. The unknown
      impurity was identified by liquid chromatography-tandem mass spectrometry using
      electrospray ionization source and Q-trap mass analyzer (LC-ESI-QT/MS/MS). Based
      on LC-MS/MS data and knowledge of the synthetic scheme of deferasirox, this
      impurity was proposed as the regio-isomer of deferasirox. Structural confirmation
      of this impurity was unambiguously carried out by synthesis followed by
      characterization using nuclear magnetic resonance (NMR), infrared spectroscopy
      (IR), mass spectrometry, elemental analysis (EA) and the impurity was confirmed
      as 2-[3,5-bis(2-hydroxy-phenyl)-[1,2,4]-triazol-1-yl]-benzoic acid (Imp-1). The
      newly developed method was validated according to ICH guidelines. The resolution
      between Imp-1 and deferasirox was found to be more than 6.0 and the detection
      limit of impurities was in the range of 0.0005-0.01%, indicating high selectivity
      and sensitivity of the newly developed method.

PMID- 22361659
TI  - A rapid LC-MS/MS method for the quantitation of a series of benzonaphthyridine
      derivatives: application to in vivo pharmacokinetic and lipophilicity studies in
      drug development.
AB  - Drug lipophilicity is a vital physicochemical parameter that influences drug
      absorption, distribution, metabolism, excretion and toxicology. A comparative
      study of a homologous series based on a pharmaceutically active drug represents a
      powerful approach to the study of the effects of drug lipophilicity. We have
      developed a rapid and sensitive LC-MS/MS method suitable for such a homologous
      series and applied it to a series of DNA binding benzonaphthyridine-based
      antitumour drugs of differing lipophilicity. The method used a gradient elution
      with a run time of 7 min for simultaneous quantitation of five analogues in a
      pooled sample. Method validation was carried out in plasma (human and mouse) and
      mouse tissues (brain, heart, kidney, liver and lung). It had a limit of
      quantitation of 0.001 MUmol/L and was linear (0.001-0.3 MUmol/L) in all matrices
      with acceptable intra- and inter-assay precision and accuracy. This method
      allowed the pharmacokinetic parameters of these compounds in mice to be related
      to their lipophilicity as determined by their partition coefficient (LogD). Both
      the plasma CL (r=0.95; P=2*10-7) and V(ss) (r=0.95; P=2*10-7) exhibited a
      significant positive correlation with LogD values after intravenous bolus
      administration to mice. Consequently the plasma mean residence time for each of
      these five analogues decreased with increasing lipophilicity. There was also a
      significant positive correlation (r=0.91; P=2*10-7) between LogD values and the
      brain to plasma AUC ratio indicating the importance of lipophilicity in the
      distribution of these compounds into the brain tissue.

PMID- 22361660
TI  - Correlation of thermal analysis and pyrolysis coupled to GC-MS in the
      characterization of tacrolimus.
AB  - In recent years, thermal analysis has assumed major role in the pharmaceutical
      industry because it can be used to evaluate the stability both in the control of
      raw materials and the finished product, having employment potential in the
      development and characterization of new products and assessment processes.
      Tacrolimus (TCR) is a macrolide lactone with potent immunosuppressive activity.
      The purpose of this study was to characterize tacrolimus raw material using
      Thermal analysis and Pyrolysis coupled to Gas chromatography-Mass spectrometry
      (Pyr-GC-MS). It was analyzed four samples of tacrolimus named TCR A, B, C and D.
      Thermal analysis experiments was performed in Shimadzu equipment, under nitrogen
      and synthetic air atmosphere in different heating rate. Pyrolysis analysis was
      conducted in isothermal conditions of 300 degrees C and 400 degrees C coupled to
      GC-MS, in which the mass spectrometer was operated in scan mode to detect ions in
      the range of mass of m/z 25-900. The thermal studies by DSC, DTA and DSC
      Photovisual showed desolvation process for all tacrolimus raw materials and TG
      dynamical demonstrated two pseudo-polymorphic forms (monohydrate and
      sesquihydrate) of tacrolimus. It was observed good correlation between the
      stoichiometric mass losses of the TG-dynamical and identification of product ion
      in Pyr-GC/MS technique. It was possible to correlate the five pyrolytic product
      ions with the Ozawa kinetic analysis from the thermal decomposition of TG
      dynamical. The thermal studies (DSC, DSC-Photovisual, DTA and TG-dynamical) were
      applied in the thermal characterization of the raw materials of tacrolimus which
      showed pseudo-polymorphic forms, which must be monitored by pharmaceutical
      industry, avoiding future problems in pharmaceutical process, chemical stability
      and bioavailability of the tacrolimus product.

PMID- 22361661
TI  - Sulfamethoxazole:hydroxypropyl-beta-cyclodextrin complex: preparation and
      characterization.
AB  - A complex of sulfamethoxazole (SMX) and hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) was developed and characterized in order to investigate their interactions in
      aqueous solution and the solid state. The SMX solubility was significantly
      increased upon complexation with HP-beta-CD, with the solubility isotherm being
      an A(N) type due to the presence of aggregates and the stability constant
      calculated for a 1:1 complex being 302 +/- 3 M-1. Fourier-transform infrared (FT
      IR) spectroscopy and scanning electron microscopy (SEM) experiments were used to
      compare the freeze-dried system with a physical mixture, and demonstrated the
      complex formation in the solid state. The differential scanning calorimetry (DSC)
      and thermogravimetric analysis (TGA) showed that the thermal stability of SMX was
      enhanced in the presence of HP-beta-CD.

PMID- 22361662
TI  - Water content determination of superdisintegrants by means of ATR-FTIR
      spectroscopy.
AB  - Water contents of superdisintegrant pharmaceutical excipients were determined by
      attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy
      using simple linear regression. Water contents of the investigated three common
      superdisintegrants (crospovidone, croscarmellose sodium, sodium starch glycolate)
      varied over a wide range (0-24%, w/w). In the case of crospovidone three
      different samples from two manufacturers were examined in order to study the
      effects of different grades on the calibration curves. Water content
      determinations were based on strong absorption of water between 3700 and 2800 cm
      1, other spectral changes associated with the different compaction of samples on
      the ATR crystal using the same pressure were followed by the infrared region
      between 1510 and 1050 cm-1. The calibration curves were constructed using the
      ratio of absorbance intensities in the two investigated regions. Using
      appropriate baseline correction the linearity of the calibration curves was
      maintained over the entire investigated water content regions and the effect of
      particle size on the calibration was not significant in the case of crospovidones
      from the same manufacturer. The described method enables the water content
      determination of powdered hygroscopic materials containing homogeneously
      distributed water.

PMID- 22361663
TI  - Analysis of a 3-D system function measured for magnetic particle imaging.
AB  - Magnetic particle imaging (MPI) is a new tomographic imaging approach that can
      quantitatively map magnetic nanoparticle distributions in vivo. It is capable of
      volumetric real-time imaging at particle concentrations low enough to enable
      clinical applications. For image reconstruction in 3-D MPI, a system function
      (SF) is used, which describes the relation between the acquired MPI signal and
      the spatial origin of the signal. The SF depends on the instrumental
      configuration, the applied field sequence, and the magnetic particle
      characteristics. Its properties reflect the quality of the spatial encoding
      process. This work presents a detailed analysis of a measured SF to give
      experimental evidence that 3-D MPI encodes information using a set of 3-D spatial
      patterns or basis functions that is stored in the SF. This resembles filling 3-D 
      k-space in magnetic resonance imaging, but is faster since all information is
      gathered simultaneously over a broad acquisition bandwidth. A frequency domain
      analysis shows that the finest structures that can be encoded with the presented
      SF are as small as 0.6 mm. SF simulations are performed to demonstrate that
      larger particle cores extend the set of basis functions towards higher resolution
      and that the experimentally observed spatial patterns require the existence of
      particles with core sizes of about 30 nm in the calibration sample. A simple
      formula is presented that qualitatively describes the basis functions to be
      expected at a certain frequency.

PMID- 22361664
TI  - HBS: a novel biometric feature based on heartbeat morphology.
AB  - In this paper, a new feature named heartbeat shape (HBS) is proposed for ECG
      based biometrics. HBS is computed from the morphology of segmented heartbeats.
      Computation of the feature involves three basic steps: 1) resampling and
      normalization of a heartbeat; 2) reduction of matching error; and 3) shift
      invariant transformation. In order to construct both gallery and probe templates,
      a few consecutive heartbeats which could be captured in a reasonably short period
      of time are required. Thus, the identification and verification methods become
      efficient. We have tested the proposed feature independently on two publicly
      available databases with 76 and 26 subjects, respectively, for identification and
      verification. The second database contains several subjects having clinically
      proven cardiac irregularities (atrial premature contraction arrhythmia).
      Experiments on these two databases yielded high identification accuracy (98% and
      99.85%, respectively) and low verification equal error rate (1.88% and 0.38%,
      respectively). These results were obtained by using templates constructed from
      five consecutive heartbeats only. This feature compresses the original ECG signal
      significantly to be useful for efficient communication and access of information
      in telecardiology scenarios.

PMID- 22361665
TI  - Artifact removal in physiological signals--practices and possibilities.
AB  - The combination of reducing birth rate and increasing life expectancy continues
      to drive the demographic shift toward an aging population. This, in turn, places
      an ever-increasing burden on healthcare due to the increasing prevalence of
      patients with chronic illnesses and the reducing income-generating population
      base needed to sustain them. The need to urgently address this healthcare "time
      bomb" has accelerated the growth in ubiquitous, pervasive, distributed healthcare
      technologies. The current move from hospital-centric healthcare toward in-home
      health assessment is aimed at alleviating the burden on healthcare professionals,
      the health care system and caregivers. This shift will also further increase the
      comfort for the patient. Advances in signal acquisition, data storage and
      communication provide for the collection of reliable and useful in-home
      physiological data. Artifacts, arising from environmental, experimental and
      physiological factors, degrade signal quality and render the affected part of the
      signal useless. The magnitude and frequency of these artifacts significantly
      increases when data collection is moved from the clinic into the home. Signal
      processing advances have brought about significant improvement in artifact
      removal over the past few years. This paper reviews the physiological signals
      most likely to be recorded in the home, documenting the artifacts which occur
      most frequently and which have the largest degrading effect. A detailed analysis
      of current artifact removal techniques will then be presented. An evaluation of
      the advantages and disadvantages of each of the proposed artifact detection and
      removal techniques, with particular application to the personal healthcare
      domain, is provided.

PMID- 22361666
TI  - Direct electrochemistry of novel affinity-tag immobilized recombinant horse heart
      cytochrome c.
AB  - During the last decade protein electrochemistry at miniaturized electrodes has
      become important not only for functional studies of the charge transfer
      properties of redox proteins but also for fostering the development of sensitive
      biosensor and bioelectronic devices. One of the major challenges in this field is
      the directed coupling between electronic and biologically active components. A
      prerequisite for a fast and reversible electron transfer between electrode and
      protein is that the protein can be bound to the electrode in a favourable
      orientation. We examined electrostatic and bioaffinity-tag binding strategies for
      the directed immobilization of horse heart cytochrome c (cytc) on gold electrode
      surfaces to achieve this goal. Horse heart cytc was expressed in E. coli either
      as non-modified or genetically modified, i.e. histidine (his)-tag containing
      protein. The his-tags were introduced at defined positions at the N- or C
      terminus of the polypeptide. It was our aim to generate tagged-versions of cytc
      that facilitate strong electronic coupling between protein and electrode and, at
      the same time, retain their catalytic and regulatory properties. The combination
      of different immobilization strategies, e.g. his-tag and electrostatic
      immobilization also opens new avenues for bivalent immobilization of proteins.
      This is of interest for molecular bioelectronic and biosensing applications where
      the proteins are immobilized between two crossing electrodes.

PMID- 22361667
TI  - Atmospheric pollution: influence on hospital admissions in paediatric rheumatic
      diseases.
AB  - OBJECTIVE: To investigate the lag structure effects from exposure to atmospheric
      pollution in acute outbursts in hospital admissions of paediatric rheumatic
      diseases (PRDs). METHODS: Morbidity data were obtained from the Brazilian
      Hospital Information System in seven consecutive years, including admissions due
      to seven PRDs (juvenile idiopathic arthritis, systemic lupus erythematosus,
      dermatomyositis, Henoch-Schonlein purpura, polyarteritis nodosa, systemic
      sclerosis and ankylosing spondylitis). Cases with secondary diagnosis of
      respiratory diseases were excluded. Daily concentrations of inhaled particulate
      matter (PM(10)), sulphur dioxide (SO(2)) nitrogen dioxide (NO(2)), ozone (O(3))
      and carbon monoxide (CO) were evaluated. Generalized linear Poisson regression
      models controlling for short-term trend, seasonality, holidays, temperature and
      humidity were used. Lag structures and magnitude of air pollutants' effects were
      adopted to estimate restricted polynomial distributed lag models. RESULTS: The
      total number of admissions due to acute outbursts PRD was 1,821. The SO(2)
      interquartile range (7.79 ug/m(3)) was associated with an increase of 1.98%
      (confidence interval 0.25-3.69) in the number of hospital admissions due to
      outcome studied after 14 days of exposure. This effect was maintained until day
      17. Of note, the other pollutants, with the exception of O(3), showed an increase
      in the number of hospital admissions from the second week. CONCLUSION: This study
      is the first to demonstrate a delayed association between SO(2) and PRD outburst,
      suggesting that oxidative stress reaction could trigger the inflammation of these
      diseases.

PMID- 22361669
TI  - Autophagy prolongs survival after NFkappaB inhibition in B-cell lymphomas.
AB  - Autophagy allows cells to survive under conditions of nutrient deprivation. We
      have demonstrated that autophagy inhibitors are synthetically lethal with
      NFkappaB inhibitors in B-cell lymphomas because the NFkappaB pathway promotes
      survival by increasing glucose import. When NFkappaB is inhibited in B-cell
      lymphoma, glucose import decreases and cells become sensitive to perturbations in
      mitochondrial metabolism and autophagy. Thus, combined inhibition of autophagy
      and NFkappaB drives cells into metabolic crisis accelerating cell death.

PMID- 22361671
TI  - Unit cell-based computer-aided manufacturing system for tissue engineering.
AB  - Scaffolds play an important role in the regeneration of artificial tissues or
      organs. A scaffold is a porous structure with a micro-scale inner architecture in
      the range of several to several hundreds of micrometers. Therefore, computer
      aided construction of scaffolds should provide sophisticated functionality for
      porous structure design and a tool path generation strategy that can achieve
      micro-scale architecture. In this study, a new unit cell-based computer-aided
      manufacturing (CAM) system was developed for the automated design and fabrication
      of a porous structure with micro-scale inner architecture that can be applied to
      composite tissue regeneration. The CAM system was developed by first defining a
      data structure for the computing process of a unit cell representing a single
      pore structure. Next, an algorithm and software were developed and applied to
      construct porous structures with a single or multiple pore design using solid
      freeform fabrication technology and a 3D tooth/spine computer-aided design model.
      We showed that this system is quite feasible for the design and fabrication of a
      scaffold for tissue engineering.

PMID- 22361672
TI  - Liver transplantation: role of immunosuppression, renal dysfunction and
      cardiovascular risk factors.
AB  - In the past decades, advances in immunosuppression, organ preservation, surgical
      techniques and better management of post-transplantation complications have led
      to improvement in survival of liver transplant patients. Such extended survival
      of liver graft recipients in their fifties and sixties has resulted in a greater
      prevalence of complications, in particular chronic kidney (CKD) and
      cardiovascular diseases (CVD). Renal failure and cardiovascular complications in
      the setting of liver transplantation are associated to an increase of morbidity
      and mortality. A 4-fold increased risk of death is reported among patients
      developing post-transplant CKD, and CVD is the leading cause of death with a
      functioning allograft, accounting for as much as 30% of post-transplant
      mortality. The onset is multifactorial, with pre-transplant conditions involved,
      including pre-transplant renal insufficiency, hepatitis C virus infection and
      pretransplant diabetes. Acute renal dysfunction in the setting of transplantation
      is also responsible of post-transplant CKD. Immunosuppressive therapy is
      primarily responsible for the development of CKD. Metabolic syndrome and its
      individual components, including diabetes mellitus, systemic hypertension,
      dyslipidemia, and obesity, are increasingly being identified as closely related
      to immunosuppressive therapy and actively contribute to cardiovascular morbidity
      and mortality in transplant patients. Treatment of modifiable risk factors is
      mandatory aiming to prevent the development and progression of serious
      complications. Early recognition, prevention and treatment of these conditions
      may further improve long-term survival after liver transplantation.

PMID- 22361673
TI  - Future challenges in renal transplantation.
AB  - There is a worldwide increase in the incidence of end-stage renal disease. Renal
      transplantation has been shown to be cost effective, prolong survival and provide
      a better quality of life in comparison to dialysis. Consequently, there has been
      a steady increase in demand for organs leading to a shortage of available
      kidneys, and an increase in transplant waiting lists. Renal transplantation is
      therefore an expanding field with a number of unique future challenges to
      address. This article outlines strategies that may be employed to expand organ
      supply in order to meet increased demand. The ethical issues surrounding this are
      also summarized. Furthermore, we highlight techniques with the potential to
      minimize peri-transplant injury to the kidney on its journey from donor to
      recipient. Current and potential future management strategies to optimize graft
      and patient survival are also discussed.

PMID- 22361674
TI  - Minimally invasive video assisted thyroidectomy versus endoscopic thyroidectomy
      via the areola approach: a retrospective analysis of safety, postoperative
      recovery, and patient satisfaction.
AB  - AIM: Minimally invasive video-assisted thyroidectomy (MIVAT) and endoscopic
      thyroidectomy through areola (ETA) access are among the endoscopic approaches for
      thyroidectomy that have been perfected, but reports comparing the two are
      lacking. This study evaluated the safety, postoperative recovery, and patient
      satisfaction of MIVAT compared with ETA. METHODS: This study included 119
      patients undergoing MIVAT and 42 patients undergoing ETA from January 2006 to
      October 2009. Operative time, complications, postoperative recovery, cosmetic
      result, and patient satisfaction were analyzed. RESULTS: The ETA group had a
      higher percentage of women (100% vs. 78.2%, P<0.05) and was younger (33.5 vs. 39
      years, P<0.05). Thyroid volume (24.5 vs. 14.5 mL, P<0.001) and nodular diameter
      (26 vs. 22 mm, P<0.05) were larger in ETA group. The MIVAT group had a shorter
      operative time (28.2 vs. 112.8 minutes) and a lower rate of intraoperative (7.2
      vs. 21.2 mL) and postoperative (0 vs. 80 mL, P<0.0001) blood loss. Rates of
      conversion and complications were similar. Postoperative pain at 12 hours was 1.9
      in MIVAT vs. 3.1 in ETA (P<0.0001). Hospitalization was 1 day in the MIVAT group
      vs. 3.5 days in ETA (P<0.0001). Patient satisfaction was similar. CONCLUSION:
      MIVAT and ETA showed similar results for safety, although ETA might be considered
      more invasive than MIVAT. Patients of both groups were equally satisfied with the
      cosmetic result. Differently from ETA, MIVAT allows total thyroidectomy to be
      performed also for malignant diseases. Although different, the two approaches
      were safe and reliable and both are valid options. Choice might depend on the
      surgeon's preference, thyroid size, type of disease, and the patient's
      expectation about cosmesis.

PMID- 22361676
TI  - Factors affecting long-term outcomes after thromboembolectomy for acute lower
      limb ischemia.
AB  - AIM: The aim of this study was to analyze factors influencing outcomes of
      surgical management for lower limb acute ischemia. METHODS: A retrospective
      analysis of 490 thromboembolectomies performed in 468 patients was conducted.
      Perioperative and follow-up results were analyzed. Univariate and multivariate
      analysis of clinical variables and patients' characteristics for the risk of
      reocclusion, amputation and mortality at 2 years were performed. Statistical
      significance was defined as a P value <0.05. RESULTS: Cumulative reocclusion,
      amputation and mortality rates at 24 months were 22.6%, 14.3% and 42.8%,
      respectively. At univariate analysis, the factors associated with increased 2
      year reocclusion rate were severity of clinical presentation, current smoking
      habit, arterial thrombosis rather than embolism, atrial fibrillation and the
      avoidance of completion angiography. All these factors except clinical
      presentation maintained significance at multivariate analysis. Factors associated
      with increased 2-year amputation rate at univariate analysis included severity of
      clinical presentation, smoke, arterial thrombosis, atrial fibrillation and
      valvulopathy. All these factors except clinical presentation and valvular defects
      maintained significance at multivariate analysis. Factors associated with
      increased 2-year mortality rate at univariate analysis included age >80 years,
      arterial thrombosis, history of peripheral arterial disease and antiplatelet
      drugs. The same factors, except antiplatelet treatment, were found to be
      significant at multivariate analysis. CONCLUSION: Surgical intervention for lower
      limb ischemia is associated with high 2-year mortality but offers good 2-year
      limb salvage. The pattern of risk factors for reocclusion and amputation rates is
      quite different from those affecting mortality. Only thrombotic aetiology is a
      significant risk factor for all the three outcomes.

PMID- 22361675
TI  - Robotic thyroid surgery using bilateral axillo-breast approach: personal initial
      experience over two years.
AB  - AIM: Although endoscopic thyroid surgery is gaining wide acceptance, however,
      manual endoscopic operation also has shown several limitations. The advent of
      robotic surgical systems, such as the da Vinci surgical system (Intuitive
      Surgical, Mountain View, CA, USA), is expected to make it possible to overcome
      some limitations of manual endoscopic operation. Herein we report a single
      surgeon (H.Y.K.)'s initial two-year experience of new robotic thyroid operations
      using the bilateral axillo-breast approach (BABA), the approach which has
      definite advantages and recently has been widely used for the traditional
      endoscopic thyroid surgery. METHODS: Between July 2008 and July 2010, 93 patients
      underwent robotic thyroid surgery using the BABA, with the da Vinci-S surgical
      system, at the Korea University Anam Hospital, Seoul, Korea. The data on the
      patients' clinicopathological characteristics, operation types, operation times,
      surgical results, postoperative hospital stays and complications were collected
      in a prospective manner, and later evaluated. RESULTS: Seventy-two total
      thyroidectomies with or without central neck dissections mostly for the papillary
      carcinomas, twenty lobectomies with or without central neck dissections for the
      minute - smaller than 0.5 cm in their maximal diameter - papillary carcinomas,
      follicular neoplasms and benign tumors, and a bilateral subtotal lobectomy for
      the multinodular goiter were performed robotically. There was no conversion of
      robotic procedure to traditional endoscopic or open procedure. The mean total
      operation time was 288.5+/-48.0 minutes. The mean number of retrieved lymph nodes
      by the central neck dissection was 5.1+/-1.97 (range, 0-12). The mean hospital
      stay of the patients was 2.8+/-1.2 days. And the mean postoperative 3rd month
      serum thyroglobulin level in patients undergone total thyroidectomy was 0.3+/
      0.14 ng/mL (range, 0.08-1.95). Three (3.2%) patients suffered from transient
      hoarseness postoperatively, but all of them recovered in three months. Transient
      hypocalcemias were observed in 17 out of 72 (23.6%) patients who had undergone
      total thyroidectomy, but none of them left permanent. No other complication, such
      as bleeding, infection, neither fluid collection, was observed. CONCLUSION: Our
      initial surgical results of robotic thyroid surgery using BABA demonstrate the
      feasibility and safety of the procedure in the treatment of benign tumors and
      early differentiated carcinomas.

PMID- 22361677
TI  - ["Skin reducing mastectomy" and immediate breast reconstruction with Becker 35
      contour profile breast implant: our experience].
AB  - AIM: We describe in this paper our experience with the technique of skin-reducing
      mastectomy in the treatment of breast cancer. METHODS: Between October 2005 and
      April 2010 in our Center 33 patients underwent breast surgery utilizing the skin
      reducing mastectomy technique and immediate breast reconstruction with
      expansor/definitive implant Becker 35 contour profile. Contralateral
      symmetrization was performed in the same operation. All selected patients
      satisfied inclusion critera either for nipple-sparing mastectomy or prophylactic
      mastectomy. We selected patients who had large ptosic breasts: areola-submammary
      fold >8 cm and jugular-nipple distance >25 cm. After histologic exam to confirm
      the lack of retroareolar tissue infiltration the nipple was preserved in a
      superior flap. RESULTS: Twenty-four out of 33 patients (72.7%) did not suffer
      from complications. In 9 patients (27.3%) we observed early complications. During
      follow-up we observed in 24 patients (72.7%) Baker I capsular contracture, in 9
      patients (27.3%) Baker II capsular contracture. Esthetic results of symmetry,
      shape and volume were good to optimal. Patients' satisfaction was similar. During
      the follow up (6-33 months, average 17.7 months) no patient suffered from breast
      cancer recurrence. CONCLUSION: The "skin-reducing mastectomy" reduces mutilation
      and unsightly scar visibility. It gives a pleasant aesthetic outcome without
      hindering oncological safety.

PMID- 22361678
TI  - Video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung
      cancer: experience with 111 consecutive patients demonstrating comorbidity.
AB  - AIM: The outcomes of video-assisted thoracoscopic lobectomy for clinical stage I
      non-small cell lung cancer (NSCLC) patients with comorbidities were examined to
      determine the technical feasibility and safety of this procedure. METHODS:
      Between January 2002 and December 2007, 111 consecutive patients with suspected
      stage I lung cancer, who individually had one or more comorbidities cited in the
      modified Kaplan-Feinstein Index, were scheduled for a video-assisted
      thoracoscopic lobectomy. The demographic, perioperative, and outcome variables
      were assessed. RESULTS: One hundred of 111 patients had non-small cell lung
      cancer. Ninety-nine patients underwent successful video-assisted thoracoscopic
      lobectomies, while there was one conversion because of a hemorrhage from the
      pulmonary artery in the early stage. Including this one conversion, no patients
      required a blood transfusion during surgery or postoperatively. There were no
      intraoperative or in-hospital deaths. No complications occurred in 78 (78.8%) of
      99 patients. Only one patient (1.0%) with a Kaplan-Feinstein Index Score of
      severe grade contracted pneumonia indicating grade 3 (severe), whereas the
      remaining 20 patients had grade 1 (mild) or 2 (moderate) complications. At a
      median follow-up of 40 months, the overall 3-year survival rates for
      postoperative stage IA (N.=52); IB (N.=26); and II or more (N.=21) were 100%;
      78%; and 71%, respectively. CONCLUSION: A video-assisted thoracoscopic lobectomy
      is therefore considered to be a feasible and safe procedure for clinical stage I
      NSCLC even in patients with comorbidities.

PMID- 22361679
TI  - Lung resection for non-small cell lung cancer after prophylactic coronary
      angioplasty and stenting: short- and long-term results.
AB  - AIM: Recent studies have reported a high incidence of perioperative in-stent
      trombosis with myocardial infarction (MI), in patients undergoing non-cardiac
      surgery, early after coronary angioplasty and stenting. The short and long-term
      results of surgery for non-small cell lung cancer (NSCLC) after prophylatic
      coronary angioplasty and stenting were analyzed. METHODS: Prospective collected
      data were examined for postoperative complications and long-term survival in 16
      consecutive patients who underwent mayor lung resection for NSCLC after
      prophylactic coronary angioplasty and stenting for significant coronary artery
      disease , from 2001 to 2008. One and two non-drug-eluting stents were placed in
      75% or (25% of the patient, respectively. All patients had four weeks of dual
      antiplatelet therapy, that was discontinued 5 days prior to surgery and replaced
      by low molecular weight heparin. Patients were keep sedated and intubated
      overnight, according to our protocol. RESULTS: There were no postoperative deaths
      nor MI. A patient experienced pulmonary embolism with moderate troponin release
      and underwent coronary angiography that showed patency of the stent. Two patients
      developed postoperative bleeding complications haemothorax requiring a re
      thoracotomy in 1, gastric bleeding requiring blood transfusion in 1. At the mean
      follow-up of 30 months (range 3-95), none of the patients showed evidence of
      myocardial ischemia, while 5 (31%) patients died, mostly (N.=4) due to distant
      metastasis. The five-year survival rate was 53%. CONCLUSION: In contrast to
      previous reports, lung resection after prophylactic coronary angioplasty and
      stenting is a safe and effective treatment for NSCLC and myocardial ischemia. The
      application of a refined protocol could be the key factor for improved results.

PMID- 22361680
TI  - [Clinical effect of bovine pericardial strips on air leak after stapled pulmonary
      resection in "frail" patients: early results].
AB  - AIM: Postoperative air leaks and in particular persistent air leaks (>5 days)
      after pulmonary resection still represent a common complication and the first
      cause of hospital stay delay. Aim of this experimental trial was to investigate
      the efficacy of the use of bovine pericardium strips (in terms of reduction of
      postoperative leakage and hospital stay) in "critical" patients (COPD, emphysema
      etc.) who underwent pulmonary resection. METHODS: From October 2010 to February
      2011, eight patients (experimental group, Group A) were preoperative selected and
      underwent pulmonary resection with bovine pericardium strips (Peri-Strips Dry;
      Synovis ). The inclusion criteria of a "frail patient" were established by a
      dedicate pneumologist according with clinical and functional data (predicted
      postoperative FEV1 ranging from 35% and 80% of the theorical predicted value).
      For comparison, from January 2010 to September 2010, we retrospectively reviewed
      the data of 28 patients who satisfied the same inclusion criteria and underwent
      pulmonary resection with standard surgical procedures. This group of patients
      represents our control group (Group B). RESULTS: There were no significant
      differences between the two groups in age, gender, preoperative risk factors for
      developing a postoperative air leak, preop FEV1 and type of resection. No
      technical deficiencies in the use of bovine pericardium strips were observed in
      Group A. Postoperative leakage was significant different in the two groups being
      persistent air leak detected in 0% in Group A versus 17.8% of Group B (P=0.046).
      Consequently, chest tube duration (6.75+/-0.84 days [Group A] vs. 9.70+/-1.26
      days (Group B), P=0.019) and hospital stay (10.13+/-0.83 days [Group A] vs.
      12.95+/-1.37 days [Group B], P=0.013) were lower in the experimental group.
      CONCLUSION: Bovine pericardium strips are safe and easy-to-do technique to reduce
      postoperative air leaks after pulmonary resection in "critical" patients.

PMID- 22361681
TI  - Melanoma metastases to the spleen: laparoscopic approach.

PMID- 22361682
TI  - Pivotal role of the RanBP9-cofilin pathway in Abeta-induced apoptosis and
      neurodegeneration.
AB  - Neurodegeneration associated with amyloid beta (Abeta) peptide accumulation,
      synaptic loss, neuroinflammation, tauopathy, and memory impairments encompass the
      pathophysiological features of Alzheimer's disease (AD). We previously reported
      that the scaffolding protein RanBP9, which is overall increased in brains of AD
      patients, simultaneously promotes Abeta generation and focal adhesion disruption
      by accelerating the endocytosis of amyloid precursor protein (APP) and beta1
      integrin, respectively. Here, we show that RanBP9 protein levels are increased by
      fourfold in FAD mutant APP transgenic mice. Accordingly, RanBP9 transgenic mice
      demonstrate significantly increased synapse loss, neurodegeneration, gliosis, and
      spatial memory deficits. RanBP9 overexpression promotes apoptosis and potentiates
      Abeta-induced neurotoxicity independent of its capacity to promote Abeta
      generation. Conversely, RanBP9 reduction by siRNA or gene dosage mitigates Abeta
      induced neurotoxicity. Importantly, RanBP9 activates/dephosphorylates cofilin, a
      key regulator of actin dynamics and mitochondria-mediated apoptosis, and siRNA
      knockdown of cofilin abolishes both Abeta and RanBP9-induced apoptosis. These
      findings implicate the RanBP9-cofilin pathway as critical therapeutic targets not
      only for stemming Abeta generation but also antagonizing Abeta-induced
      neurotoxicity.

PMID- 22361684
TI  - Synthesis of terphenyl benzimidazoles as tubulin polymerization inhibitors.
AB  - A series of new terphenyl benzimidazoles (3a-z and 3aa-ad) were synthesized and
      evaluated for their anticancer activity. All the 30 compounds have shown moderate
      to good anticancer potency, however some of the compounds (3j, 3m-t and 3aa-ad)
      exhibited prominent anticancer potency with GI(50) values ranging from <0.1 to
      9.72 MUM. These compounds exhibit G2/M phase arrest and the analysis of tubulin
      by Western blot experiments in case of 3t and 3ad shows the disturbances that are
      caused in the ratio of soluble versus polymerized tubulin in cells. Compounds 3t
      and 3ad are the most promising candidates amongst the series and has the
      potential to be taken up for further detailed studies either alone or in
      combination with the existing therapies.

PMID- 22361683
TI  - NOXA, a sensor of proteasome integrity, is degraded by 26S proteasomes by an
      ubiquitin-independent pathway that is blocked by MCL-1.
AB  - Ubiquitin (Ub)-mediated proteasome-dependent proteolysis is critical in
      regulating multiple biological processes including apoptosis. We show that the
      unstructured BH3-only protein, NOXA, is degraded by an Ub-independent mechanism
      requiring 19S regulatory particle (RP) subunits of the 26S proteasome,
      highlighting the possibility that other unstructured proteins reported to be
      degraded by 20S proteasomes in vitro may be bona fide 26S proteasome substrates
      in vivo. A lysine-less NOXA (NOXA-LL) mutant, which is not ubiquitinated, is
      degraded at a similar rate to wild-type NOXA. Myeloid cell leukemia 1, but not
      other anti-apoptotic BCL-2 family proteins, stabilizes NOXA by interaction with
      the NOXA BH3 domain. Depletion of 19S RP subunits, but not alternate proteasome
      activator REG subunits, increases NOXA half-life in vivo. A NOXA-LL mutant, which
      is not ubiquitinated, also requires an intact 26S proteasome for degradation.
      Depletion of the 19S non-ATPase subunit, PSMD1 induces NOXA-dependent apoptosis.
      Thus, disruption of 26S proteasome function by various mechanisms triggers the
      rapid accumulation of NOXA and subsequent cell death strongly implicating NOXA as
      a sensor of 26S proteasome integrity.

PMID- 22361685
TI  - Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape
      , 2D-fingerprint- and pharmacophore-based virtual screening approach.
AB  - We report the first application of ligand-based virtual screening (VS) methods
      for discovering new compounds able to inhibit both human immunodeficiency virus
      type 1 (HIV-1) reverse transcriptase (RT)-associated functions, DNA polymerase
      and ribonuclease H (RNase H) activities. The overall VS campaign consisted of two
      consecutive screening processes. In the first, the VS platform Rapid Overlay of
      Chemical Structures (ROCS) was used to perform in silico shape-based similarity
      screening on the NCI compounds database in which a hydrazone derivative,
      previously shown to inhibit the HIV-1 RT, was chosen. As a result, 34 hit
      molecules were selected and assayed on both RT-associated functions. In the
      second, the 4 most potent RT inhibitors identified were selected as queries for
      parallel VS performed by combining shape-based, 2D-fingerprint and 3D
      pharmacophore VS methods. Overall, a set of molecules characterized by new
      different scaffolds were identified as novel inhibitors of both HIV-1 RT
      associated activities in the low micromolar range.

PMID- 22361686
TI  - Design, synthesis and biological evaluation of novel (E)-alpha-benzylsulfonyl
      chalcone derivatives as potential BRAF inhibitors.
AB  - Activating mutations in the BRAF serine/threonine kinase are found in more than
      70% of human melanomas, >90% of which are BRAF(V600E). It provides new
      therapeutic opportunities in malignant melanoma. In silico and in vitro screening
      of our compound collection has identified Hit 2 as BRAF(V600E) inhibitor. Based
      on its structure, a series of novel (E)-alpha-benzylsulfonyl chalcone derivatives
      (13-40) were designed and synthesized. Compound 38 exhibited the most potent
      inhibitory activity with an IC(50) value of 0.17 MUM for BRAF(V600E) and GI(50)
      value of 0.52 MUM for mutant BRAF-dependent cells. The results of cell based pERK
      activity and cellular selectivity suggested that those compounds could
      selectively inhibit proliferation of mutant BRAF-dependent melanoma cell line
      through inhibition of oncogenic BRAF.

PMID- 22361687
TI  - Reversible formation of a PdC(x) phase in Pd nanoparticles upon CO and O2
      exposure.
AB  - The structure and chemical composition of Pd nanoparticles exposed to pure CO and
      mixtures of CO and O(2) at elevated temperatures have been studied in situ by a
      combination of X-ray Diffraction and X-ray Photoelectron Spectroscopy in
      pressures ranging from ultra high vacuum to 10 mbar and from room temperature to
      a few hundred degrees celsius. Our investigation shows that under CO exposure,
      above a certain temperature, carbon dissolves into the Pd particles forming a
      carbide phase. Upon exposure to CO and O(2) mixtures, the carbide phase forms and
      disappears reversibly, switching at the stoichiometric ratio for CO oxidation.
      This finding opens new scenarios for the understanding of catalytic oxidation of
      C-based molecules.

PMID- 22361688
TI  - Screening for gynaecologic cancers in genetically predisposed women.
AB  - Hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colon
      cancer syndrome are the two most important syndromes responsible for inherited
      cancers in gynaecology. Genetic testing is available for both these syndromes.
      Breast cancer gene testing is affordable and easy in women with ancestry where
      the mutation patterns are known, whereas other population groups need full gene
      screening. Hereditary non-polyposis colon cancer syndrome can now be diagnosed
      more frequently with the use of immunohistochemistry. Ovarian cancer risk is high
      in hereditary breast and ovarian cancer syndromes, and advanced screening
      techniques should be used when preventive surgery is not an option. Early
      detection techniques offer less protection than prophylactic removal, but enable
      women to retain their reproductive organs. Oophorectomy has the advantage of
      reducing breast cancer risk. In colorectal cancer syndromes, the risk for
      endometrial and ovarian cancer is much elevated. These risks should be recognised
      and addressed as these diseases are easy to prevent.

PMID- 22361689
TI  - A search for BACE inhibitors reveals new biosynthetically related pyrrolidones,
      furanones and pyrroles from a southern Australian marine sponge, Ianthella sp.
AB  - Fractionation of a southern Australian marine sponge, Ianthella sp., yielded
      sixteen metabolites including a new class of pyrrolidone, ianthellidones A-F (1
      6), a new class of furanone, ianthellidones G-H (7-8), new and known lamellarins,
      lamellarins O1 (9), O2 (10), O (11) and Q (12), plus the known 4
      hydroxybenzaldehyde (13), 4-hydroxybenzoic acid (14), 4-methoxybenzoic acid (15)
      and ethyl 4-hydroxybenzoate (16). Structures for all Ianthella metabolites were
      determined by detailed spectroscopic analysis, supported by a plausible
      biosynthetic relationship. The ianthellidones were non-cytotoxic towards two
      human colon cancer cell lines (SW620 and SW620 Ad300), as well as Gram +ve and
      Gram -ve bacteria, and a fungus. Ianthellidone F (6) and lamellarins O2 (10) and
      O (11) displayed modest BACE inhibitory properties (IC(50) > 10 MUM), while
      lamellarin O1 (9) was more potent (IC(50) < 10 MUM). Lamellarin O (11) exhibited
      modest cytotoxicity towards SW620 and SW620 Ad300 cell lines (IC(50) > 22 MUM),
      was an inhibitor of the multi-drug resistance efflux pump P-glycoprotein, and
      displayed selective growth inhibitory activity against the Gram +ve bacterium
      Bacillus subtilis (ATCC 6633) (IC(50) 2.5 MUM).

PMID- 22361691
TI  - Neuromuscular manifestations of HIV/AIDS.
AB  - The human immunodeficiency virus (HIV) epidemic, now entering its fourth decade,
      affects approximately 33 million people living in both developed and resource
      limited countries. Neurological complications of the peripheral nervous system
      are common in HIV-infected patients, and neuromuscular pathology is associated
      with significant morbidity. Peripheral neuropathy is the most common
      neuromuscular manifestation observed in HIV/AIDS, and in the antiretroviral era,
      its prevalence has increased. The purpose of this review was to describe the
      clinical spectrum of neuromuscular disorders in the setting of HIV infection and
      to provide an approach to diagnosis and management.

PMID- 22361690
TI  - Rituximab and mycophenolate combination therapy in refractory dermatomyositis
      with multiple autoimmune disorders.
AB  - We report a case of dermatomyositis associated with rheumatoid arthritis,
      Hashimoto thyroiditis, and diabetes mellitus responsive only to combination of
      rituximab with mycophenolate. A 42-year-old woman presented with proximal muscle
      weakness, myalgias, fever, night sweats, and shortness of breath. Creatinine
      kinase was 8155 IU/L, and muscle biopsy was diagnostic of dermatomyositis. She
      was started on glucocorticoids; her systemic symptoms improved, but her muscle
      weakness persisted. She was serially treated with intravenous immunoglobulin,
      azathioprine, and mycophenolate mofetil without improvement in her weakness. She
      responded dramatically to combination therapy with rituximab and mycophenolate,
      with improvement in strength and normalization of creatinine kinase. She has been
      well controlled on rituximab infusion every 6 months and maintenance
      mycophenolate mofetil.

PMID- 22361692
TI  - Plasma exchange versus intravenous immunoglobulin for myasthenia gravis crisis:
      an acute hospital cost comparison study.
AB  - OBJECTIVE: To compare the short-term financial costs of treating a patient in
      myasthenia gravis crisis with intravenous immunoglobulin (IVIG) versus plasma
      exchange. METHODS: An itemized comparative cost-minimization analysis of IVIG
      versus plasma exchange for myasthenia gravis crisis was performed. Calculations
      were based on each therapy's implementation cost, associated hospitalization
      times, and predicted cost to treat known complications. A cost superiority
      determination was proposed based on the total cost profile of each therapy.
      RESULTS: The difference in total cost favored IVIG over plasma exchange with an
      average savings of $22,326 per patient. Sensitivity analysis demonstrated that
      overall costs are highly dependent on IVIG dosing, hospital lengths of stay, and
      the number of plasma exchange days required. CONCLUSIONS: The use of IVIG for
      myasthenia gravis crisis may be a short-term cost minimizing therapy compared
      with plasma exchange. Additional prospective studies are required to evaluate the
      extended cost profile and efficacy of these therapies.

PMID- 22361693
TI  - Musculotendinous infraspinatus rupture and shoulder weakness.
AB  - We report a patient with bilateral simultaneous onset of weakness of shoulder
      lateral rotation due to musculotendinous infraspinatus rupture that occurred
      after shoulder steroid injections. Disruption of the musculotendinous junction of
      the infraspinatus is a rare recently described entity. Electromyography is
      normal, and magnetic resonance image findings are characteristic.

PMID- 22361695
TI  - Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine
      synovial fluid proteomics.
AB  - Osteoarthritis (OA) and osteochondrosis (OC) are two of the main challenges in
      orthopedics, whose definitive diagnosis is usually based on
      radiographic/arthroscopic evidences. Their early diagnosis should allow
      preventive or timely therapeutic actions, which are generally precluded from the
      poor relationships occurring between symptomatologic and radiographic evidences.
      These limitations should be overcome by improving the knowledge on articular
      tissue metabolism and on molecular factors regulating its normal homeostasis,
      also identifying novel OA and OC biomarkers suitable for their earlier diagnoses,
      whenever clinical/pathological inflammatory scenarios between these joint
      diseases seem somewhat related. To identify proteins involved in their aetiology
      and progression, we undertook a differential proteomic analysis of equine
      synovial fluid (SF), which compared the protein pattern of OA or OC patients with
      that of healthy individuals. Deregulated proteins in OA and OC included
      components related to inflammatory state, coagulation pathways, oxidative stress
      and matrix damage, which were suggestive of pathological alterations in articular
      homeostasis, plasma-SF exchange, joint nutritional status and vessel
      permeability. Some proteins seemed commonly deregulated in both pathologies
      indicating that, regardless of the stimulus, common pathways are affected and/or
      the animal joint uses the same molecular mechanisms to restore its homeostasis.
      On the other hand, the increased number of deregulated proteins observed in OA
      with respect to OC, together with their nature, confirmed the high inflammatory
      character of this disease. Some deregulated proteins in OA found a verification
      by analyzing the SF of injured arthritic joints following autologous conditioned
      serum treatment, an emergent therapy that provides positive results for both
      human and equine OA. Being the horse involved in occupational/sporting activities
      and considered as an excellent animal model for human joint diseases, our data
      provide suggestive information for tentative biomedical extrapolations, allowing
      to overcome the limitations in joint size and workload that are typical of other
      small animal models.

PMID- 22361696
TI  - Systematic validation of antibody binding and protein subcellular localization
      using siRNA and confocal microscopy.
AB  - We have developed a platform for validation of antibody binding and protein
      subcellular localization data obtained from immunofluorescence using siRNA
      technology combined with automated confocal microscopy and image analysis. By
      combining the siRNA technology with automated sample preparation, automated
      imaging and quantitative image analysis, a high-throughput assay has been set-up
      to enable confirmation of accurate protein binding and localization in a
      systematic manner. Here, we describe the analysis and validation of the
      subcellular location of 65 human proteins, targeted by 75 antibodies and silenced
      by 130 siRNAs. A large fraction of (80%) the subcellular locations, including
      locations of several previously uncharacterized proteins, could be confirmed by
      the significant down-regulation of the antibody signal after the siRNA silencing.
      A quantitative analysis was set-up using automated image analysis to facilitate
      studies of targets found in more than one compartment. The results obtained using
      the platform demonstrate that siRNA silencing in combination with quantitative
      image analysis of antibody signals in different compartments of the cells is an
      attractive approach for ensuring accurate protein localization as well as
      antibody binding using immunofluorescence. With a large fraction of the human
      proteome still unexplored, we suggest this approach to be of great importance
      under the continued work of mapping the human proteome on a subcellular level.

PMID- 22361697
TI  - Comparison of ubiquitous antibiotic-resistant Enterobacteriaceae populations
      isolated from wastewaters, surface waters and drinking waters.
AB  - This study aimed at assessing the role of ubiquitous (non-Escherichia coli)
      Enterobacteriaceae in the dissemination of antimicrobial resistance through the
      urban water cycle. Enterobacteriaceae isolated from a municipal wastewater
      treatment plant (111 isolates), urban water streams (33 isolates) and drinking
      water (123 isolates) were compared in terms of: (i) genera distribution, (ii)
      resistance to 12 antibiotics, and (iii) class 1 and class 2 integrons. The
      predominant bacterial genera were the same in the different types of water,
      although with a distinct pattern of species. The most prevalent resistance
      phenotypes were observed for amoxicillin, ticarcillin, cephalothin and
      sulphamethoxazole (24-59% in the three types of water). No resistance against
      ceftazidime or meropenem was observed. Resistance to cephalothin, amoxicillin and
      sulphamethoxazole was significantly more prevalent in drinking water, water
      streams and wastewater, respectively, than in the other types of water. It was
      possible to recognize antibiotic-resistance associations, namely for the pairs
      streptomycin-tetracycline (positive) and ticarcillin-cephalotin (negative). Class
      1 and/or class 2 integrons with similar gene cassettes were detected in the three
      types of water. This study demonstrated that Enterobacteriaceae are important
      vehicles of antibiotic resistance, namely in drinking water.

PMID- 22361698
TI  - Disinfection efficacy of chlorine and peracetic acid alone or in combination
      against Aspergillus spp. and Candida albicans in drinking water.
AB  - The aim of the present study was to evaluate the fungicidal activity of chlorine
      and peracetic acid in drinking water against various pathogenic Aspergillus spp.
      and Candida albicans strains. A. nidulans exhibited the greatest resistance,
      requiring 10 ppm of chlorine for 30 min contact time for a complete inactivation.
      Under the same experimental conditions, peracetic acid was even less fungicidal.
      In this case, A. niger proved to be the most resistant species (50 ppm for 60 min
      for complete inactivation). All Aspergillus spp. were insensitive to 10 ppm even
      with extended exposure (>5 h). The combination of chlorine and peracetic acid
      against Aspergillus spp. did not show synergistic effects except in the case of
      A. flavus. Complete growth inhibition of C. albicans was observed after about 3 h
      contact time with 0.2 ppm. C. albicans was less sensitive to peracetic acid.
      Hence the concentrations of chlorine that are usually present in drinking water
      distribution systems are ineffective against several Aspergillus spp. and
      peracetic acid cannot be considered an alternative to chlorine for disinfecting
      drinking water. The combination of the two biocides is not very effective in
      eliminating filamentous fungi at the concentrations permitted for drinking water
      disinfection.

PMID- 22361699
TI  - Inactivation of Ascaris eggs in water using sequential solar driven photo-Fenton
      and free chlorine.
AB  - Sequential helminth egg inactivation using a solar driven advanced oxidation
      process (AOP) followed by chlorine was achieved. The photo-assisted Fenton
      process was tested alone under different H(2)O(2) and/or Fe(II) concentrations to
      assess its ability to inactivate Ascaris suum eggs. The effect of free chlorine
      alone was also tested. The lowest egg inactivation results were found using
      Fe(II) or H(2)O(2) separately (5 and 140 mmol L(-1), respectively) in dark
      conditions, which showed about 28% inactivation of helminth eggs. By combining
      Fe(II) and H(2)O(2) at the same concentrations described earlier, 55% of helminth
      egg inactivation was achieved. By increasing the reagent's concentration two
      fold, 83% egg inactivation was achieved after 120 min of reaction time. Process
      efficiency was enhanced by solar excitation. Using solar disinfection only, the
      A. suum eggs inactivation reached was the lowest observed (58% egg inactivation
      after 120 min (120 kJ L(-1))), compared with tests using the photo-Fenton
      process. The use of the photo-Fenton reaction enhanced the process up to over 99%
      of egg inactivation after 120 kJ L(-1) when the highest Fe(II) and H(2)O(2)
      concentration was tested. Practically no effect on the helminth eggs was observed
      with free chlorine alone after 550 mg min L(-1) was used. Egg inactivation in the
      range of 25-30% was obtained for sequential processes (AOP then chlorine) using
      about 150 mg min L(-1).

PMID- 22361700
TI  - Removal of Cryptosporidium and polystyrene microspheres from swimming pool water
      with sand, cartridge, and precoat filters.
AB  - Cryptosporidium has caused the majority of waterborne disease outbreaks in
      treated recreational water venues in the USA for many years running. This
      research project evaluated some common US swimming pool filters for removing
      Cryptosporidium oocysts, 5-um diameter polystyrene microspheres, and 1-um
      diameter polystyrene microspheres. A 946 L hot tub with interchangeable sand,
      cartridge, and precoat filters was used at room temperature for this research.
      Simulated pool water for each experiment was created from Charlotte, NC (USA) tap
      water supplemented with alkalinity, hardness, chlorine, and a mixture of
      artificial sweat and urine. Precoat (i.e., diatomaceous earth and perlite)
      filters demonstrated pathogen removal efficiencies of 2.3 to 4.4 log (or 99.4
      99.996%). However, sand and cartridge filters had average Cryptosporidium
      removals of 0.19 log (36%) or less. The combined low filter removal efficiencies
      of sand and cartridge filters along with the chlorine-resistant properties of
      Cryptosporidium oocysts could indicate a regulatory gap warranting further
      attention and having significant implications on the protection of public health
      in recreational water facilities. The 5-um microspheres were a good surrogate for
      Cryptosporidium oocysts in this study and hold promise for use in future research
      projects, field trials, and/or product testing on swimming pool filters.

PMID- 22361701
TI  - Removal of estrogens and estrogenicity through drinking water treatment.
AB  - Estrogenic compounds have been shown to be present in surface waters, leading to
      concerns over their possible presence in finished drinking waters. In this work,
      two in vitro human cell line bioassays for estrogenicity were used to evaluate
      the removal of estrogens through conventional drinking water treatment using a
      natural water. Bench-scale studies utilizing chlorine, alum coagulation, ferric
      chloride coagulation, and powdered activated carbon (PAC) were conducted using
      Ohio River water spiked with three estrogens, 17beta-estradiol, 17alpha
      ethynylestradiol, and estriol. Treatment of the estrogens with chlorine, either
      alone or with coagulant, resulted in approximately 98% reductions in the
      concentrations of the parent estrogens, accompanied by formation of by-products.
      The MVLN reporter gene and MCF-7 cell proliferation assays were used to
      characterize the estrogenic activity of the water before and after treatment. The
      observed estrogenic activities of the chlorinated samples showed that
      estrogenicity of the water was reduced commensurate with removal of the parent
      estrogen. Therefore, the estrogen chlorination by-products did not contribute
      appreciably to the estrogenic activity of the water. Coagulation alone did not
      result in significant removals of the estrogens. However, addition of PAC, at a
      typical drinking water plant dose, resulted in removals ranging from
      approximately 20 to 80%.

PMID- 22361702
TI  - Defensive spending on tap water substitutes: the value of reducing perceived
      health risks.
AB  - We examine factors that explain consumer spending on tap water substitutes using
      information from a national survey undertaken with a representative set of
      Canadian respondents. We develop a model to predict the percentage of households
      that undertake such spending for the purpose of reducing perceived health risks
      from tap water consumption. Using results from the model we estimate the
      magnitude of defensive expenditures to be over half a billion dollars (2010 US$)
      per year for Canada, as a whole. This is equivalent to approximately $48 per
      household per year or about $19 per person per year. Residents of Ontario, the
      province in which an Escherichia coli incident took place in 2000, have the
      highest willingness-to-pay of approximately $60 per household per year.

PMID- 22361703
TI  - Drinking water consumption patterns in Canadian communities (2001-2007).
AB  - A pooled analysis of seven cross-sectional studies from Newfoundland and
      Labrador, Waterloo and Hamilton Regions, Ontario and Vancouver, East Kootenay and
      Northern Interior Regions, British Columbia (2001 to 2007) was performed to
      investigate the drinking water consumption patterns of Canadians and to identify
      factors associated with the volume of tap water consumed. The mean volume of tap
      water consumed was 1.2 L/day, with a large range (0.03 to 9.0 L/day). In-home
      water treatment and interactions between age and gender and age and bottled water
      use were significantly associated with the volume of tap water consumed in
      multivariable analyses. Approximately 25% (2,221/8,916) of participants were
      classified as bottled water users, meaning that 75% or more of their total daily
      drinking water intake was bottled. Approximately 48.6% (4,307/8,799) of
      participants used an in-home treatment method to treat their tap water for
      drinking purposes. This study provides a broader geographic perspective and more
      current estimates of Canadian water consumption patterns than previous studies.
      The identified factors associated with daily water consumption could be
      beneficial for risk assessors to identify individuals who may be at greater risk
      of waterborne illness.

PMID- 22361704
TI  - Presence of human noro- and adenoviruses in river and treated wastewater, a
      longitudinal study and method comparison.
AB  - Norovirus (NoV) is one of the most common causative agents of waterborne
      gastroenteritis outbreaks. The main objective of the study was to determine the
      presence of human NoVs in river water and in treated wastewater (TW) released
      into the river. During a one-year survey in 2007/2008, NoVs were detected in
      30.8% of river samples (20/65), and 40.5% of TW samples (17/45) with a real-time
      reverse transcription-PCR assay. NoVs were present in the river water in the
      winter and spring, coinciding with the NoV epidemiological peak in the community
      and the presence of NoVs in TW. Later in 2009, the concentration method used, pre
      filtration with a Waterra filter combined with filtration through a negatively
      charged membrane, was evaluated against glass wool filtration and freeze-drying
      for the detection of adenoviruses in river water. The virus amounts measured
      varied greatly depending on the virus concentration method. The continued
      monitoring in the spring of 2009 also revealed that the average concentration of
      noro- and adenoviruses in TW was 2.64 * 10(3) and 1.29 * 10(4) pcr units per mL,
      respectively. No correlation between the presence of viruses and Escherichia coli
      was found. These results may be useful for risk assessment studies.

PMID- 22361705
TI  - Effect of environmental parameters on the inactivation of the waterborne pathogen
      Campylobacter in a Mediterranean river.
AB  - Campylobacter is a major waterborne pathogen that can be found in rivers of the
      Mediterranean area. Characteristics of these rivers change throughout the seasons
      due to variations in environmental parameters. As these variations may affect
      water survival of Campylobacter, we analyzed it in the Llobregat River using
      three approaches whose complexity increase progressively: (i) river water
      microcosms in the laboratory subjected to varying temperatures; (ii) in situ
      experiments carried out in the river, in which bacteria were exposed to varying
      levels of environmental parameters; and (iii) monitoring of thermotolerant
      Campylobacter in the river over two years. Campylobacter was quantified using the
      most probable number (MPN) method. The results showed that an increase in water
      temperature accelerates Campylobacter inactivation, measured as the loss of
      culturability. In situ experiments revealed that inactivation rates were also
      affected by sunlight, but not by pH, oxygen concentration or water conductivity.
      These observations are supported by the seasonality detected in Llobregat River.
      Campylobacter inactivation was fastest in spring and summer, when temperature and
      solar radiation were at their highest. The results highlight the importance of
      considering the inactivation rates in natural conditions to improve the
      monitoring of this pathogen and thus evaluate properly the health risk associated
      to water.

PMID- 22361706
TI  - Microbiological and chemical indicators of water quality in indoor hotel swimming
      pools before and after training of swimming pool operators.
AB  - The present study was undertaken in order to determine the quality of indoor pool
      waters in hotels along the Croatian coast. We wanted to assess the risks of
      exposure to microbial and chemical contaminants and find out if training pool
      operators to use a quality assurance system, that we developed, influenced
      hygienic conditions and water quality in swimming pools or not. The samples were
      analysed for free chlorine, pH and several microbiological indicators according
      to standard laboratory methodologies. Of 1,329 samples tested, 276 were found to
      be unacceptable either by chemical (148) or microbiological parameters (128).
      After training, the proportion of unacceptable samples dropped by 23.5%, mostly
      according to the free chlorine values. According to our results, most of the
      microbiologically unacceptable samples had chlorine levels within the recommended
      range but their pH values were too high. A free chlorine level below 0.2 mg/L was
      found in 106 (82.8%) microbiologically unacceptable samples suggesting the need
      for maintaining the lower limit at least above 0.2 mg/L in order to reduce
      microbial risks to a more acceptable level. This measure combined with training
      of pool operators might result in reduced health risks in pool waters.

PMID- 22361707
TI  - A community-based approach to promote household water treatment in Rwanda.
AB  - Treatment of drinking water at the household level is one of the most effective
      preventive interventions against diarrhea, a leading cause of illness and death
      among children in developing countries. A pilot project in two districts in
      Rwanda aimed to increase use of Sur'Eau, a chlorine solution for drinking water
      treatment, through a partnership between community-based health insurance schemes
      and community health workers who promoted and distributed the product. Evaluation
      of the pilot, drawing on a difference-in-differences design and data from pre-
      and post-pilot household surveys of 4,780 households, showed that after 18 months
      of pilot implementation, knowledge and use of the product increased significantly
      in two pilot districts, but remained unchanged in a control district. The pilot
      was associated with a 40-42 percentage point increase in ever use, and 8-9
      percentage points increase in use of Sur'Eau at time of the survey (self-reported
      measures). Our data suggest that exposure to inter-personal communication on
      Sur'Eau and hearing about the product at community meetings and health centers
      were associated with an increase in use.

PMID- 22361708
TI  - Phenotypic stress response of Pseudomonas aeruginosa following culture in water
      microcosms.
AB  - The purpose of the present study was to explore the potential behavioural changes
      of Pseudomonas aeruginosa following growth in different aquatic environmental
      conditions. To achieve this, P. aeruginosa was cultured in various water
      microcosms for 12 months under fixed (pH, nutrients and temperature) factors. P.
      aeruginosa responses to these conditions were investigated using colony
      morphotype, biochemical and enzymatic characterisation, pyocin typing,
      serotyping, sensitivity to different classes of antibiotics and molecular
      identification. Results show that starvation in water microcosms lead to unusual
      phenotypes. Of interest is that the pyocin changed from 24/n in the wild type to
      83/a following culture in the water microcosms, and the serotype changed from O6
      in the wild type to O1 in microcosm-cultured P. aeruginosa. Furthermore, the
      starvation period in various aquatic microcosms enhanced the resistance of P.
      aeruginosa against beta-lactam antibiotics. Compared to the other aquatic
      environments, the seawater microcosm produced the greatest amount of variations
      in P. aeruginosa. Overall, data demonstrated a high adaptability of P. aeruginosa
      to environmental changes. This may explain the unusual antibiotic-resistant
      phenotypes belonging to P. aeruginosa species, and their capacity for spreading
      that leads to human infections.

PMID- 22361709
TI  - Screening of recreational areas of rivers for potentially pathogenic free-living
      amoebae in the suburbs of Tehran, Iran.
AB  - A survey was conducted to determine the presence of free-living amoebae (FLA),
      especially Acanthamoeba and Naegleria, in river recreation areas in Tehran
      Province, Iran. All rivers surveyed were associated with human activity, and two
      were also a source of municipal tap water. Fifty-five water samples from 10 major
      rivers were screened for FLA and identified by morphological characters, PCR
      amplification targeting specific genes for Acanthamoeba (DF3 region of Rns gene)
      and other FLA (ITS PCR), and homology analysis. The percentage of positive FLA
      isolates was 27.3%, of which 80% were Acanthamoeba, assigned to the T4 and T15
      genotype, and 20% were Naegleria. Isolation of Acanthamoeba T4 genotype (91.7%)
      from recreation areas could be a health threat and a sanitary risk associated
      with human activity where young people and tourists congregate in summer. Posting
      of warning signs and education of high-risk individuals are important for disease
      prevention. To the best of our knowledge this is the first report of genotype T15
      (clustered with A. jacobsi) identified in Iran and the first report of the
      distribution of FLA such as Naegleria (N. pagei, N. clarki and N. fultoni) in
      recreation areas in rivers of Tehran Province using molecular methods.

PMID- 22361710
TI  - Total and infectious Cryptosporidium oocyst and total Giardia cyst concentrations
      from distinct agricultural and urban contamination sources in Eastern Canada.
AB  - Cryptosporidium and Giardia (oo)cyst concentrations are frequently used for
      assessing drinking water safety. The widely used USEPA Method 1623 provides total
      counts of (oo)cysts, but may not be accurate for human health risk
      characterization, since it does not provide infectivity information. The total
      counts and infectious fraction of Cryptosporidium oocysts and the total counts of
      Giardia cysts were assessed in major fecal pollution sources. Fresh calf and cow
      feces, their manure, and the discharge point were sampled in a small rural sub
      watershed (n = 20, 21, 10, 10). Median concentrations for total (oo)cysts were
      higher in calves (333 oocysts g(-1); 111 cysts g(-1)) than in cows (52 oocysts g(
      1); 7 cysts g(-1)). Infectious oocysts were found in 17 (7%) of the samples and
      none were found in manure or at the discharge point. Urban sources were sampled
      in the influent and effluent (n = 19, 18) of two wastewater treatment plants.
      Peak concentrations were 533 oocysts L(-1) and 9,010 cysts L(-1) for influents
      and 89 oocysts L(-1) and 472 cysts L(-1) for effluents. Infectious oocyst
      fractions varied from below the detection limit to 7-22% in the effluent and
      influent respectively. These infectious fractions are significantly lower than
      those currently used for quantitative microbial risk assessment estimates.

PMID- 22361711
TI  - Association of blood pressure and metabolic syndrome components with magnesium
      levels in drinking water in some Serbian municipalities.
AB  - Chronic exposure to insufficient levels of magnesium (Mg) in drinking water
      increases the risk of magnesium deficiency and its association with hypertension,
      dyslipidemia and type 2 diabetes mellitus. The aim of the study was to assess the
      potential association of mineral contents in drinking water with blood pressure
      and other components of metabolic syndrome (MetS) (BMI as measure of obesity,
      triglycerides, glucose, and insulin resistance, index-HOMA IR), in a healthy
      population. This study was conducted in three randomly selected municipalities
      (Pozarevac, Grocka and Banovci), and recruited 90 healthy blood donors, aged 20
      50 years. The Pozarevac area had a four times higher mean Mg level in drinking
      water (42 mg L(-1)) than Grocka (11 mg L(-1)). Diastolic blood pressure was
      lowest in subjects from Pozarevac. Serum Mg (sMg) was highest, and serum
      Ca(2+)/Mg (sCa/Mg) lowest in subjects from Pozarevac, and after adjustment for
      confounders (age, gender, BMI), only total cholesterol and sMg levels were
      independent predictors of diastolic blood pressure, sMg levels were independent
      predictors of triglycerides, and sCa/Mg predicted glucose levels. These results
      suggest that Mg supplementation in areas of lower magnesium levels in drinking
      water may be an important measure in the prevention of hypertension and MetS in
      general.

PMID- 22361712
TI  - Characterization of microbial communities distributed in the groundwater pumped
      from deep tube wells in the Kathmandu Valley of Nepal.
AB  - Although groundwater is a major water supply source in the Kathmandu Valley of
      Nepal, it is known that the groundwater has significant microbial contamination
      exceeding the drinking water quality standard recommended by the World Health
      Organization (WHO), and that this has been implicated in causing a variety of
      diseases among people living in the valley. However, little is known about the
      distribution of pathogenic microbes in the groundwater. Here, we analysed the
      microbial communities of the six water samples from deep tube wells by using the
      16S rRNA gene sequences based culture-independent method. The analysis showed
      that the groundwater has been contaminated with various types of opportunistic
      microbes in addition to fecal microbes. Particularly, the clonal sequences
      related to the opportunistic microbes within the genus Acinetobacter were
      detected in all samples. As many strains of Acinetobacter are known as multi-drug
      resistant microbes that are currently spreading in the world, we conducted a
      molecular-based survey for detection of the gene encoding carbapenem-hydrolysing
      beta-lactamase (bla(oxa-23-like) gene), which is a key enzyme responsible for
      multi-drug resistance, in the groundwater samples. Nested polymerase chain
      reaction (PCR) using two specific primer sets for amplifying bla(oxa-23-like)
      gene indicated that two of six groundwater samples contain multi-drug resistant
      Acinetobacter.

PMID- 22361713
TI  - Probe sialidase substrate specificity using chemoenzymatically synthesized
      sialosides containing C9-modified sialic acid.
AB  - A library of alpha2-3- and alpha2-6-linked sialyl galactosides containing C9
      modified sialic acids was synthesized from C6-modified mannose derivatives using
      an efficient one-pot three-enzyme system. These sialosides were used in a high
      throughput sialidase substrate specificity assay to elucidate the importance of
      C9-OH in sialidase recognition.

PMID- 22361714
TI  - Clinical results of revision shoulder arthroplasty using the reverse prosthesis.
AB  - BACKGROUND: Success of revision shoulder arthroplasty using an unconstrained
      prosthesis depends on an intact rotator cuff and satisfactory bone quantity.
      However, the reverse shoulder arthroplasty can stabilize a glenohumeral joint
      even in patients with rotator cuff deficiency and bone deficits, resulting in
      improved outcomes. MATERIALS AND METHODS: Thirty shoulders in 28 patients with a
      failed arthroplasty were investigated consecutively between 2005 and 2008. All
      shoulders had significant rotator cuff deficiency without glenoid bone loss.
      Revision arthroplasty using the reverse prosthesis was performed with a minimum
      of 2 years of follow-up. Concomitant glenoid reconstructions with tricortical
      iliac crest bone grafting were necessary in 12 shoulders. RESULTS: The average
      adjusted Constant score improved from 24% to 65% and the American Shoulder and
      Elbow Surgeons (ASES) score improved from 55 to 72 (P < .0001). Average active
      forward flexion increased from 42 degrees  to 106 degrees  (P < .0001). The
      average ASES pain score improved from 6.6 to 1.6 (P < .0001). The overall
      complication rate was 50%, and 7 patients (23%) required reoperation. Overall, 24
      of 30 shoulders (80%) were very satisfied or satisfied. CONCLUSION: Reverse
      shoulder arthroplasty can be an efficacious salvage procedure in the management
      of failed arthroplasty due to rotator cuff-related instability or bone defects,
      or both. Structural bone grafting on the glenoid side is successful at managing
      large defects, producing similar or better clinical outcomes compared with
      patients without bone loss. Although the operation is associated with a
      considerable complication rate, 80% of patients were satisfied with the results
      of the procedure, and 29 of 30 shoulders had a stable prosthesis.

PMID- 22361715
TI  - Reinforced fascia patch limits cyclic gapping of rotator cuff repairs in a human
      cadaveric model.
AB  - BACKGROUND: Scaffolds continue to be developed and used for rotator cuff repair
      augmentation, but clinical or biomechanical data to inform their use are limited.
      We have developed a reinforced fascia lata patch with mechanical properties to
      meet the needs of musculoskeletal applications. The objective of this study was
      to assess the extent to which augmentation of a primary human rotator cuff repair
      with the reinforced fascia patch can reduce gap formation during in vitro cyclic
      loading. MATERIALS AND METHODS: Nine paired human cadaveric shoulders were used
      to investigate the cyclic gap formation and failure properties of augmented and
      non-augmented rotator cuff repairs with loading of 5 to 180 N for 1000 cycles.
      RESULTS: Augmentation significantly decreased the amount of gap formation at
      cycles 1, 10, 100, and 1000 compared with non-augmented repairs (P < .01). The
      mean gap formation of the augmented repairs was 1.8 mm after the first cycle of
      pull (vs 3.6 mm for non-augmented repairs) and remained less than 5 mm after 1000
      cycles of loading (4.7 mm for augmented repairs vs 7.3 mm for non-augmented
      repairs). Furthermore, all augmented repairs were able to complete the 1000-cycle
      loading protocol, whereas 3 of 9 non-augmented repairs failed before completing
      1000 loading cycles. CONCLUSIONS: This study supports further investigation of
      reinforced fascia patches to provide mechanical augmentation, minimize tendon
      retraction, and possibly reduce the incidence of rotator cuff repair failure.
      Future investigation in animal and human studies will be necessary to fully
      define the efficacy of the reinforced fascia device in a biologic healing
      environment.

PMID- 22361716
TI  - Evaluation of dislocation position in patients with recurrent anterior shoulder
      dislocation.
AB  - BACKGROUND: The usual mechanism of anterior shoulder dislocation is widely
      believed to be a combination of glenohumeral joint abduction, extension, and
      external rotation forces, even though no published reports to date have
      investigated the arm position of anterior shoulder dislocation in detail.
      Understanding the exact position of anterior shoulder dislocations is important
      for the management of anterior shoulder instability. MATERIALS AND METHODS: The
      study included 40 shoulders of 38 patients (32 males, 6 females), aged 28.0
      (range, 13-73) years with symptomatic post-traumatic recurrent anterior shoulder
      instability. While patients were under general anesthesia, but before shoulder
      stabilizing surgery, we evaluated the angle of external rotation with 90 degrees 
      elevation in the scapular plane at which the humeral head showed anterior
      translations over the glenoid rim. RESULTS: The center of anterior instability at
      90 degrees  elevation in the scapular plane was at 25.9 degrees  of external
      rotation. Anterior translations were detected in the range of 3.4 degrees  of
      internal rotation to 55.1 degrees  of external rotation, and no shoulders (except
      one) showed anterior translation at maximal external rotation. CONCLUSIONS: Gross
      anterior translation was seen in the middle range of rotation at approximately 25
      degrees  of external rotation, and anterior translation decreased close to the
      end of external and internal rotation. Shoulders with grade III translation
      showed anterior translation in a wider range of rotation, especially in external
      rotation. These data will help to further our understanding of the management and
      the prevention of anterior shoulder dislocations.

PMID- 22361717
TI  - Reverse total shoulder arthroplasty for failed shoulder arthroplasty.
AB  - INTRODUCTION: Shoulder arthroplasty provides excellent outcomes for most
      patients; however, a subset of these patients with a failed arthroplasty will
      require revision. Recently, the reverse total shoulder arthroplasty (rTSA) has
      been used in these difficult clinical situations. Therefore, we sought to examine
      our initial experience using rTSA as a treatment for failed shoulder
      arthroplasty. METHODS: During a 5-year period, 31 patients (mean age, 68.7 years)
      underwent rTSA for treatment of a failed shoulder arthroplasty and their
      presurgical and operative data were analyzed. Of the 31 patients, 28 were
      available for an average follow-up of 40.7 months. Their outcomes were assessed
      with American Shoulder and Elbow Surgeons (ASES), University of California-Los
      Angeles (UCLA), and Simple Shoulder Test (SST) scores, and the visual analog
      scale (VAS) for pain. RESULTS: Compared with preoperative status, there were
      statistically significant improvements in all outcome measurements, including the
      ASES (24.0 to 66.2), UCLA (7.4 to 23.5), SST (1.5 to 7.6), and VAS (7.0 to 2.6).
      Active forward elevation improved from 44 degrees  preoperatively to 108 degrees 
      postoperatively (P < .001). Results were rated as good or excellent by 19
      patients (67.9%), satisfactory by 4 (14.3%), and unsatisfactory by 5 (17.8%).
      Among the types of failed arthroplasty, patients with failed TSA noted the
      greatest improvement in their outcome, but this improvement was not statistically
      significant. CONCLUSIONS: The data suggest that patients can expect improved
      functional outcome and decreased pain after revision of previous arthroplasty to
      rTSA and that this procedure can provide a reliable salvage option for a
      challenging clinical problem.

PMID- 22361718
TI  - The effects of arm elevation on the 3-dimensional acromiohumeral distance: a
      biplane fluoroscopy study with normative data.
AB  - HYPOTHESIS AND BACKGROUND: Narrowing of the subacromial space has been implicated
      in several shoulder pathologies. However, the location of the minimum distance
      points during clinical testing has not been defined. We sought to measure the in
      vivo minimum distance and location of the minimum distance points on the acromion
      and proximal humerus during arm elevation. METHODS: Eight healthy male subjects
      (mean age, 30 years) underwent a dynamic in vivo biplane fluoroscopy assessment
      of scaption and forward elevation. For each frame, the 3-dimensional position and
      orientation of the humerus and scapula were determined, and the acromiohumeral
      distance (AHD) was measured as the shortest distance between the acromion and
      proximal humerus. RESULTS: The minimum AHD was 2.6 +/- 0.8 mm during scaption and
      1.8 +/- 1.2 mm during forward flexion at elevation angles of 83 degrees  +/- 13
      degrees  and 97 degrees  +/- 23 degrees , respectively. The minimum distance
      point was located on the articular surface of the humeral head from the neutral
      arm position until 34 degrees  +/- 8 degrees  for scaption and 36 degrees  +/- 6
      degrees  for forward flexion. Upon further elevation, the minimum distance point
      was located within the footprint of the supraspinatus muscle until 72 degrees  +/
      12 degrees  for scaption and 65 degrees  +/- 8 degrees  for forward flexion. At
      greater elevation angles, the minimum distance points were between the acromion
      and the proximal humeral shaft, distal from the greater tuberosity. CONCLUSIONS:
      The shortest AHD was at approximately 90 degrees  of arm elevation. The AHD was
      no longer measured intra-articularly or within the supraspinatus footprint above
      approximately 70 degrees  of arm elevation.

PMID- 22361719
TI  - Intracardiac metastasis from germ cell testicular tumor.
AB  - Intracardiac metastases of germ cell testicular tumors are not commonly seen in
      clinical practice. The clinical presentation of right-sided heart metastases
      ranges widely. Depending upon its size and intracardiac location, it could be
      highly symptomatic, leading to a congestive heart failure, pulmonary embolism,
      and death, or completely asymptomatic. Improved imaging techniques and treatment
      strategies demonstrate that right-sided heart metastasis should be considered a
      potentially dangerous but treatable disease. Presented is the case of a 24-year
      old man with a testicular nonseminomatous germ cell tumor, which after
      metastasizing in the right atrium differentiated into a teratoma and resulted in
      an inflow obstruction of the right ventricle.

PMID- 22361720
TI  - Myocardial infarction due to coronary thrombosis in a patient with Henoch
      Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is characterized by vasculitic involvement of
      small-sized vessels and results in multisystem manifestations. Cardiac
      involvement is extremely rare and myocardial infarction with coronary thrombus
      formation in those patients has also rarely been reported. Herein, we report a 33
      year-old man with acute myocardial infarction due to coronary thrombus formation
      and HSP.

PMID- 22361721
TI  - Ovariectomy in the developing rat decelerates cortical spreading depression in
      adult brain.
AB  - The brain of mammals is one important target organ for the action of gonadal
      steroids and, when occurring during development, this hormonal influence may
      result in important repercussion on the brain electrophysiological properties at
      adulthood, some of which depending on the brain excitability. Here we have
      characterized in early-ovariectomized adult rats the brain ability to propagate
      the excitability-related phenomenon known as cortical spreading depression (CSD),
      as an index of the cerebral electrophysiological effects of the early-induced
      absence of the ovarian hormones. Wistar female rat pups (7-day old) underwent
      bilateral ovariectomy (Ovx group; n=21) or Sham surgery (Sham group; n=22), or no
      surgery (Naive group; n=22). When the pups became adult (90-130 days), they were
      submitted to the recording of CSD (electrocorticogram and slow DC-voltage
      variation) in two points of the cortical surface during 4h. Compared with both
      Naive and Sham controls, bilateral ovariectomy early in life resulted in
      significantly higher body weights (from days 50-65 onwards) and severely reduced
      uterus weights at adulthood. Furthermore, in the Ovx animals the amplitudes and
      durations of the DC-potential changes of CSD were higher, and the CSD propagation
      velocities were reduced. Another group of rats ovariectomized in adulthood did
      not present such CSD alterations. It is concluded that ovariectomy during brain
      development is causally associated with the CSD changes in the adult brain,
      indicating a long-lasting effect, which we suggest as being related to the long
      term suppression of the action of the ovarian hormones on brain excitability.

PMID- 22361722
TI  - [Hereditary forms of ovarian cancer].
AB  - Approximately 5 to 10 % of all ovarian cancers arise in the setting of a major
      genetic predisposition. The two main hereditary forms of ovarian adenocarcinomas
      are the hereditary breast/ovarian cancers associated with a BRCA1 or BRCA2 gene
      mutation and the Lynch syndrome associated with a MLH1, MSH2, MSH6 or PMS2 gene
      mutation. Their identification and the characterization of a causative germline
      mutation are crucial and have a major impact for affected women and their
      relatives in terms of medical management. The aim of this review is to indicate
      cancer risks associated with these two entities, to evaluate their contribution
      in the pathogenesis of ovarian cancers and to indicate the clinical data
      suggestive of these diagnoses, the validated indications for genetic analyses and
      the current management guidelines. We will also illustrate the diagnostic
      strategy by reporting a clinical observation.

PMID- 22361723
TI  - Symmetry, chirality and crystalline tendency: the polymorphism of
      triacylglycerols.
AB  - The physical properties of foods containing fat are often dependent on the
      polymorphism of the constituent triacylglycerols (TAG). This is illustrated by
      the favourable physical and sensory properties associated with the beta' form for
      margarine and butter and the beta(V) form for chocolate. Recent investigations
      have revealed that the stereochemistry of TAG molecules has a profound influence
      on their polymorphism. For instance, a pure enantiomer of TAG (sn-10:0-10:0-16:0)
      was beta'-tending while the corresponding racemic mixture (rac-10:0-10:0-16:0)
      was beta-tending. In addition, the binary phase diagram for mixtures of the two
      enantiomers, sn-10:0-10:0-16:0 and sn-16:0-10:0-10:0, showed the formation of a
      eutectic (metastable beta'-form conglomerate) and a molecular compound (stable
      beta-form racemic compound). At heart, these differences in polymorph and
      crystalline tendency stem from differences in the stereochemistry of the unit
      cell -i.e. both enantiomers in the beta unit cell, one enantiomer in the beta'
      unit cell. Information on the relative stereochemical arrangement of molecules
      within the unit cell is also available from the crystallographic space group.
      This information (determined by X-ray diffraction) is available for a number of
      beta- and beta'-tending, chiral and achiral TAG systems. Like crystalline
      tendency (discussed previously), space group data indicates that the unit cell
      for TAG in the beta' polymorph contains only one stereoisomer whereas the unit
      cell for TAG in the beta polymorph contains both stereoisomers (conformers in
      achiral and enantiomers in chiral systems). Therefore, based on the current data,
      the stereochemical arrangement of TAG molecules in the unit cell is associated
      with the polymorphic form of the solid - both stereoisomers in the beta form and
      one stereoisomer in the beta' form. This perspective clearly explains the
      observed differences in polymorphic behavior for enantiopure and racemic TAG
      including the beta'-stability of enantiopure systems. As a result, the current
      descriptive mechanism for TAG polymorphism is vastly improved when the
      stereochemical orientation of the constituent TAG molecules is considered.

PMID- 22361725
TI  - The challenge of staying happier: testing the Hedonic Adaptation Prevention
      model.
AB  - The happiness that comes from a particular success or change in fortune abates
      with time. The Hedonic Adaptation Prevention (HAP) model specifies two routes by
      which the well-being gains derived from a positive life change are eroded--the
      first involving bottom-up processes (i.e., declining positive emotions generated
      by the positive change) and the second involving top-down processes (i.e.,
      increased aspirations for even more positivity). The model also specifies two
      moderators that can forestall these processes--continued appreciation of the
      original life change and continued variety in change-related experiences. The
      authors formally tested the predictions of the HAP model in a 3-month three-wave
      longitudinal study of 481 students. Temporal path analyses and moderated
      regression analyses provided good support for the model. Implications for the
      stability of well-being, the feasibility of "the pursuit of happiness," and the
      appeal of overconsumption are discussed.

PMID- 22361724
TI  - Chronic stimulation of cultured neuronal networks boosts low-frequency
      oscillatory activity at theta and gamma with spikes phase-locked to gamma
      frequencies.
AB  - Slow wave oscillations in the brain are essential for coordinated network
      activity but have not been shown to self-organize in vitro. Here, the development
      of dissociated hippocampal neurons into an active network with oscillations on
      multi-electrode arrays was evaluated in the absence and presence of chronic
      external stimulation. Significant changes in signal power were observed in the
      range of 1-400 Hz with an increase in amplitude during bursts. Stimulation
      increased oscillatory activity primarily in the theta (4-11 Hz) and slow gamma
      (30-55 Hz) bands. Spikes were most prominently phase-locked to the slow gamma
      waves. Notably, the dissociated network self-organized to exhibit sustained
      delta, theta, beta and gamma oscillations without input from cortex, thalamus or
      organized pyramidal cell layers.

PMID- 22361726
TI  - MKP-1 coordinates ordered macrophage-phenotype transitions essential for stem
      cell-dependent tissue repair.
AB  - Re-establishing tissue homoeostasis in response to injury requires infiltration
      of inflammatory cells and activation of resident stem cells. However, full tissue
      recovery also requires that the inflammation is resolved. While it is known that
      disturbing the interactions between inflammatory cells and tissue resident cells
      prevents successful healing, the molecular mechanisms underlying the paracrine
      interactions between these cell types are practically unknown. Here, and in a
      recent study, we provide mechanistic evidence that macrophages control stem cell
      dependent tissue repair. In particular, we found that the temporal spacing of the
      pro- to anti-inflammatory macrophage polarization switch is controlled by the
      balance of p38 MAPK (termed here p38) and the MAPK phosphatase MKP-1 during the
      muscle healing process. Moreover, we demonstrate a new function for MKP-1
      regulated p38 signaling in deactivating macrophages during inflammation
      resolution after injury. Specifically, at advanced stages of regeneration, MKP-1
      loss caused an unscheduled "exhaustion-like" state in muscle macrophages, in
      which neither pro- nor anti-inflammatory cytokines are expressed despite
      persistent tissue damage, leading to dysregulated reparation by the tissue stem
      cells. Mechanistically, we demonstrate that p38 and MKP-1 control the AKT pathway
      through a miR-21-dependent PTEN regulation. Importantly, both genetic and
      pharmacological interference with the individual components of this pathway
      restored inflammation-dependent tissue homeostasis in MKP-1-deficient mice and
      delayed inflammation resolution and tissue repair dysregulation in wild-type
      mice. Because the process of tolerance to bacterial infection involves a
      progressive attenuation of pro-inflammatory gene expression, we discuss here the
      potential similarities between the mechanisms underlying inflammation resolution
      during tissue repair and those controlling endotoxin tolerance.

PMID- 22361727
TI  - BMP signaling in rats with TNBS-induced colitis following BMP7 therapy.
AB  - Beyond stimulating bone formation, bone morphogenetic proteins (BMPs) are
      important in development, inflammation, and malignancy of the gut. We have
      previously shown that BMP7 has a regenerative, anti-inflammatory, and
      antiproliferative effect on experimental inflammatory bowel disease (IBD) in
      rats. To further investigate the BMP signaling pathway we monitored the effect of
      BMP7 therapy on the BMP signaling components in the rat colon during different
      stages of experimentally induced colitis by 2,4,6-trinitrobenzene sulfonic acid
      (TNBS). The results showed a significantly decreased BMP7 expression in the acute
      phase, followed by a significantly increased BMP2 and decreased BMP6 expression
      during the chronic phase of colitis. BMP7 therapy influenced the expression of
      several BMPs with the most prominent effect on downregulation of BMP2 and
      upregulation of BMP4 in the chronic phase of colitis. Importantly, connective
      tissue growth factor and noggin expression were elevated in the acute stage and
      significantly decreased upon BMP7 therapy. BMP receptor I expression was
      unchanged, whereas BMP receptor II was decreased at day 2 and increased at days
      14 and 30 of TNBS inflammation. However, an opposite pattern of expression
      following BMP7 therapy has been observed. BMP7 increased the expression of BR
      Smad including Smad3 and Smad4. Inhibitory Smads were increased in colitis and
      significantly decreased following BMP7 therapy at later stages of the disease. We
      suggest that BMP signaling was altered during TNBS-induced colitis and was
      recovered with BMP7 administration, suggesting that IBD is a reversible process.

PMID- 22361728
TI  - Divergent fate and origin of neurosphere-like bodies from different layers of the
      gut.
AB  - Enteric neural stem cells (ENSCs) are a population of neural crest-derived
      multipotent stem cells present in postnatal gut that may play an important role
      in regeneration of the enteric nervous system. In most studies, these cells have
      been isolated from the layer of the gut containing the myenteric plexus. However,
      a recent report demonstrated that neurosphere-like bodies (NLBs) containing ENSCs
      could be isolated from mucosal biopsy specimens from children, suggesting that
      ENSCs are present in multiple layers of the gut. The aim of our study was to
      assess whether NLBs isolated from layers of gut containing either myenteric or
      submucosal plexus are equivalent. We divided the mouse small intestine into two
      layers, one containing myenteric plexus and the other submucosal plexus, and
      assessed for NLB formation. Differences in NLB density, proliferation, apoptosis,
      neural crest origin, and phenotype were investigated. NLBs isolated from the
      myenteric plexus layer were present at a higher density and demonstrated greater
      proliferation, lower apoptosis, and higher expression of nestin, p75, Sox10, and
      Ret than those from submucosal plexus. Additionally, they contained a higher
      percentage of neural crest-derived cells (99.4 +/- 1.5 vs. 0.7 +/- 1.19% of Wnt1
      cre:tdTomato cells; P < 0.0001) and produced more neurons and glial cells than
      those from submucosal plexus. NLBs from the submucosal plexus layer expressed
      higher CD34 and produced more smooth muscle-like cells. NLBs from the myenteric
      plexus layer contain more neural crest-derived ENSCs while those from submucosal
      plexus appear more heterogeneous, likely containing a population of mesenchymal
      stem cells.

PMID- 22361729
TI  - Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations
      during crypt regeneration after irradiation.
AB  - Recent identification of intestinal epithelial stem cell (ISC) markers and
      development of ISC reporter mice permit visualization and isolation of
      regenerating ISCs after radiation to define their functional and molecular
      phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice
      demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas
      enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We
      hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit
      enhanced proliferative capacities, and adopt a distinct gene expression profile
      associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal
      radiation and studied between days 3 and 9 postradiation. Radiation-induced
      changes in number, growth, and transcriptome of the different Sox9-EGFP cell
      populations were determined by histology, flow cytometry, in vitro culture
      assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low
      cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified
      additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC
      markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs.
      Irradiation caused complete crypt loss, followed by expansion and
      hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only
      Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in
      culture, whereas during regeneration both Sox9-EGFP Low and High cells formed
      organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells
      exhibited transcriptomic changes linked to p53-signaling and ISC-like functions
      including DNA repair and reduced oxidative metabolism. These findings support a
      model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells
      contain radiation-activatable cells with ISC characteristics, and both
      participate in crypt regeneration.

PMID- 22361730
TI  - Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk
      stimulates colon cancer cell proliferation.
AB  - The aryl hydrocarbon receptor (AhR) mediates many toxic effects of environmental
      pollutants. AhR also interacts with multiple growth factor-driven signaling
      pathways. In the course of examining effects of growth factors on proliferation
      of human colon cancer cells, we identified cross talk between AhR and the
      epidermal growth factor receptor (EGFR). In the present work, we explored
      underlying signal transduction mechanisms and functional consequences of this
      interaction. With the use of two human colon cancer cell lines, H508 and SNU-C4,
      we examined the effects of AhR ligands including 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) on cell proliferation and activation of EGFR, ERK1/2, and Src
      kinases. In colon cancer cells, 5-day incubation with TCDD stimulated a twofold
      dose-dependent increase in cell proliferation that was detectable with 1 nM and
      maximal with 30 nM TCDD. TCDD induced dose- and time-dependent phosphorylation of
      EGFR (Tyr845) and ERK1/2; maximal phosphorylation was observed 5 to 10 min after
      addition of 30 nM TCDD. Both TCDD-induced ERK1/2 phosphorylation and cell
      proliferation were abolished by AhR small interfering RNA, AhR-specific inhibitor
      CH223191, Src kinase inhibitor PP2, neutralizing antibodies against matrix
      metalloproteinase 7, heparin-binding-EGF-like growth factor and EGFR, EGFR
      inhibitors (AG1478 and PD168393), and MEK1 inhibitor PD98059.
      Coimmunoprecipitation experiments revealed that AhR forms a protein complex with
      Src and regulates Src activity by phosphorylating Src (Tyr416) and
      dephosphorylating Src (Tyr527). These data support novel observations that, in
      human colon cancer cells, Src-mediated cross talk between aryl hydrocarbon and
      EGFR results in ERK1/2 activation, thereby stimulating cell proliferation.

PMID- 22361731
TI  - Esophageal functional impairments in experimental eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite
      the increasing diagnosis of EoE globally, the causes of EoE and other esophageal
      eosinophilic disorders are not clearly understood. EoE pathology includes
      accumulation of inflammatory cells (e.g., eosinophils, mast cells),
      characteristic endoscopic features (e.g., furrows, the formation of fine
      concentric mucosal rings, exudates), and functional impairments (e.g., esophageal
      stricture, dysmotility). We hypothesized that the esophageal structural pathology
      and functional impairments of EoE develop as a consequence of the effector
      functions of the accumulated inflammatory cells. We analyzed eosinophils (anti
      major basic protein immunostaining), esophageal stricture (X-ray barium
      swallowing), and esophageal motility (isometric force) in two established
      transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel
      eosinophil-deficient model (DeltadblGATA/CD2-IL-5). Herein, we show the
      following: 1) CD2-IL-5 and doxycycline (DOX)-induced rtTA-CC10-IL-13 mice have
      chronic eosinophilic and mast cell esophageal inflammation; 2) eosinophilic
      esophageal inflammation promotes esophageal stricture in both transgenic murine
      models; 3) the eosinophil-deficient DeltadblGATA/CD-2-IL-5 mice were protected
      from the induction of stricture, whereas the eosinophil-competent CD2-IL-5 mice
      develop esophageal stricture; 4) esophageal stricture is not reversible in DOX
      induced rtTA-CC10-IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5
      transgene-induced (CD2-IL-5) EoE evidences esophageal dysmotility (relaxation and
      contraction) that is independent of the eosinophilic esophageal inflammation: CD2
      IL-5 and DeltadblGATA/CD2-IL-5 mice have comparable esophageal dysmotility.
      Collectively, our present study directly implicates chronic eosinophilic
      inflammation in the development of the esophageal structural impairments of
      experimental EoE.

PMID- 22361732
TI  - L-arginine uptake by cationic amino acid transporter 2 is essential for colonic
      epithelial cell restitution.
AB  - Restoration of the colonic epithelial barrier is an important response during
      colitis. L-arginine (L-Arg) is a semiessential amino acid that reduces murine
      colitis induced by Citrobacter rodentium. Cationic amino acid transporter (CAT)
      proteins increase L-Arg uptake into cells. L-Arg is utilized to produce nitric
      oxide (NO), by inducible NO synthase (iNOS), or L-ornithine (L-Orn) by arginase
      (Arg) enzymes. The latter is followed by generation of polyamines by ornithine
      decarboxylase (ODC) and L-proline (L-Pro) by ornithine aminotransferase (OAT). We
      show that L-Arg enhanced epithelial restitution in conditionally immortalized
      young adult mouse colon (YAMC) cells in a wound repair model, and in isolated
      mouse colonic epithelial cells (CECs), using a cell migration assay. Restitution
      was impaired by C. rodentium. Wounding induced CAT2, and inhibition of L-Arg
      uptake by the competitive inhibitor L-lysine (L-Lys) or by CAT2 shRNA, but not
      CAT1 shRNA, decreased restitution. Migration was impaired in CECs treated with L
      Lys or from CAT2(-/-) mice. Wounding increased Arg1 expression, and inhibition of
      arginase with S-(2-boronoethyl)-L-cysteine (BEC) or Arg1 shRNA inhibited
      restitution in YAMC cells; cell migration in CECs was also impaired by BEC.
      Inhibition of ODC or iNOS did not alter restitution. L-Orn or L-Pro restored
      restitution in cells treated with BEC or Arg1 shRNA, whereas the polyamine
      putrescine had no benefit. Wounding increased OAT levels, OAT shRNA inhibited
      restitution, and L-Pro restored restitution in cells with OAT knockdown. Uptake
      of L-Arg, and its metabolism by Arg1 to L-Orn and conversion to L-Pro by OAT is
      essential for colonic epithelial wound repair.

PMID- 22361734
TI  - Cyclin dependent kinases in cancer: potential for therapeutic intervention.
AB  - Cell cycle progression through each phase is regulated by heterodimers formed by
      cyclin-dependent kinases (CDKs) and their regulatory partner proteins, the
      cyclins. Together they coordinate the cellular events through cell cycle. De
      regulation of cell-cycle control due to aberrant CDK activity is a common feature
      of most cancer types. Intensive research on small molecules that target cell
      cycle regulatory proteins has led to the identification of many candidate
      inhibitors that are able to arrest proliferation and induce apoptosis in
      neoplastic cells as a promising strategy to treat cancer. Interestingly, cyclin
      dependent kinases (CDKs) have also been proposed as therapeutic targets for
      Multiple Myeloma (MM). Overexpression and aberrant expression of the cyclins,
      specifically the D cyclins is seen in the majority of MM underscoring the value
      of exploring CDK inhibition in MM which currently remains an incurable neoplastic
      plasma-cell disorder. It is characterized by clonal proliferation of malignant
      plasma cells in the bone marrow microenviroment and associated organ dysfunction.
      Recent preclinical and early clinical data explore several CDK inhibitors in the
      context of MM. This review will provide an overview of the main classes of CDK
      inhibitors with a focus on their mechanism of action and discuss clinical and
      pharmacological implications of CDK inhibitors as possible therapeutic approaches
      for the treatment of cancer with specific consideration to MM.

PMID- 22361733
TI  - p63 expression correlates with sensitivity to the Eg5 inhibitor ZD4877 in bladder
      cancer cells.
AB  - Antimitotics such as taxanes are being considered as alternatives to conventional
      cisplatin-based chemotherapy in patients with bladder cancer, but the molecular
      determinants of sensitivity or resistance to these agents in bladder cancer cells
      have not been defined. Here we examined the cytotoxic effects of a novel
      antimitotic, the Eg5 inhibitor AZD4877, in a molecularly diverse panel of human
      bladder cancer cell lines. The cells displayed heterogeneous responses to the
      drug that correlated closely with sensitivity to docetaxel but not with
      sensitivity to cisplatin. Global gene expression profiling identified p63 as the
      top gene that was differentially expressed between sensitive and resistant cell
      lines. Stable knockdown of p63 inhibited cell death induced by either AZD4877 or
      docetaxel and was associated with decreased proliferation and decreased
      expression of c-myc. Furthermore, c-myc knockdown also rendered cells resistant
      to AZD4877 or docetaxel. Together, our results implicate p63 and its downstream
      target c-myc as determinants of sensitivity to anti-mitotics in bladder cancer
      cells. Our data also suggest that anti-mitotics and cisplatin target different
      subsets of bladder cancer cells, a conclusion that may have important
      implications for the therapy of muscle-invasive bladder cancers.

PMID- 22361735
TI  - Transvaginal cholecystectomy without laparoscopic support using prototype
      flexible endoscopic instruments in a porcine model.
AB  - BACKGROUND: Transvaginal cholecystectomy with laparoscopic assistance has been
      performed safely in humans. The next goal was to develop a natural orifice
      transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy
      without laparoscopic instruments using one flexible endoscope and flexible
      accessories. The aim of the study was to test the feasibility of the procedure in
      a survival porcine model. METHODS: Cholecystectomies were attempted in five 88
      130-lb. pigs with a planned 2-week survival. Prototype flexible instruments
      (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access,
      dissection, and removal of the gallbladder via the transvaginal route. RESULTS:
      Cholecystectomy could be completed without abdominal incision using prototype
      instruments in four out of five pigs. The cystic duct could be exposed with a
      flexible hook knife and clips applied. The steerable trocar improved stability
      and the precision of the dissection. The critical view was established in all
      five pigs. Dissection of the gallbladder off the liver bed was imprecise
      resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At
      necropsy, all clips on the cystic duct were secure and no bile leak, bowel
      injury, or adhesions were present. CONCLUSIONS: NOTES cholecystectomy without
      laparoscopic support is feasible but challenging using prototype flexible
      endoscopic devices. A prototype clip applier was effective in controlling the
      cystic duct. Further improvements in instrument design to ensure precision and
      safety are needed before flexible devices should be used for pure NOTES
      procedures in humans.

PMID- 22361736
TI  - Epidermal Langerhans cells in small fiber neuropathies.
AB  - We quantified the immune histiocytic Langerhans cells (LCs) in skin biopsy
      samples of patients with distal small fiber neuropathy (SFN). Patients were
      divided according to the presence or absence of neuropathic pain (burning pain)
      assessed by a visual analogue scale (VAS). We studied 13 diabetic patients (pain
      DSFN), 7 nondiabetic patients (pain-SFN) who reported relevant neuropathic pain
      (VAS >= 3), and 6 nondiabetic patients without neuropathic pain (no-pain-SFN).
      Using double immunofluorohistochemistry with the PGP 9.5 and the langerin/CD207,
      we quantified the intraepidermal nerve fibers density (IENFD) and LCs per square
      millimeter in the epidermis. A group of 10 skin samples from healthy subjects
      served as controls. Confocal analysis was performed to evaluate LC PGP 9.5
      immunoreactivity. We found a mean value of 334.3LC/mm(2) in controls,
      310.2LC/mm(2) in no-pain-SFN, 329.6LC/mm(2) in pain-SFN and 484.3LC/mm(2) in pain
      DSFN (analysis of variance; P=.01). In patients, analysis of covariance adjusted
      by different covariables showed that the presence of diabetes (F=5.2, P=.03) was
      associated with an increased number of LC/mm(2). There was a negative correlation
      between the IENFD and the number of LCs (r(2)=-0.13, P=.03). No statistically
      significant differences were found among groups of subjects either for the co
      localization or for the number of LCs that were PGP 9.5-immunoreactive (analysis
      of variance; P>.05). These results indicate that patients with neuropathic pain
      in the context of SFN, specially those who had diabetes (DSFN), had an increased
      number of LCs in the epidermis that may play a role in the generation or
      maintenance of neuropathic pain.

PMID- 22361737
TI  - De novo intestine-specific transcriptome of the brown planthopper Nilaparvata
      lugens revealed potential functions in digestion, detoxification and immune
      response.
AB  - The brown planthopper (Nilaparvata lugens, BPH) is the most serious rice plant
      pests in Asia. In this study, we performed transcriptome-wide analysis on BPH
      intestine. We obtained more than 26 million sequencing reads that were then
      assembled into 53,553 unigenes with a mean size of 388 bp. Based on similarity
      search with the nucleotide sequences available at NCBI, BPH intestine-specific
      transcriptome analysis identified 21,405 sequences. Assembled sequences were
      annotated with gene description, gene ontology and clusters of orthologous group
      terms. The digestion-, defense- and xenobiotic metabolism-related genes were
      abundantly detected in the transcripts from BPH intestine. Many novel genes
      including 33 digestion-related genes, 25 immune responsive genes and 27
      detoxification-related genes are first reported here. We investigated the gene
      expression patterns at the transcript levels in different tissues by quantitative
      real-time PCR analysis, which revealed that some genes had intestine-specific
      expression, implicating their potential significance for BPH management.

PMID- 22361739
TI  - Extended Szabo (anchor-wire) technique concept for stent implantation in
      congenital heart lesions.
AB  - We report the usefulness of the Szabo (anchor-wire) technique and two
      modifications of such based on the same concept for stent implantation in
      congenital heart lesions. The modifications of the original technique are related
      to the localization of the cell of the stent through which the anchor wire, which
      stops the stent advancement, is introduced: proximal in the original technique
      and central or distal in the reported modifications. These techniques were
      performed in six patients: in two to maintain permeability of the ductus
      arteriosus, in three to achieve a fenestration of the interatrial septum, and in
      one to implant a stent in a right ventricle-to-pulmonary artery conduit close to
      the bifurcation. We describe the technique as well as the most important
      difficulties and complications encountered. The Szabo or anchor-wire technique
      concept is a new tool for stent implantation that can provide more accurate stent
      positioning compared with conventional angiographically guided implantation in
      different congenital heart defects. As with any new tool, this technique demands
      a learning curve and knowledge of potential complications.

PMID- 22361740
TI  - Ultrasensitive and selective detection of nicotinamide adenine dinucleotide by
      target-triggered ligation-rolling circle amplification.
AB  - An ultrasensitive fluorescence assay for nicotinamide adenine dinucleotide
      (NAD(+)) was developed by target-triggered ligation-rolling circle amplification
      (L-RCA). This novel approach can detect as low as 1 pM NAD(+), much lower than
      those of previously reported biosensors, and exhibits high discrimination ability
      even against 200 times excess of NAD(+) analogs.

PMID- 22361738
TI  - Single-nucleotide polymorphism rs2290692 in the 3'UTR of ITPKC associated with
      susceptibility to Kawasaki disease in a Han Chinese population.
AB  - Kawasaki disease (KD) is characterized by acute systemic vasculitis and
      frequently is complicated by coronary artery lesions (CALs). The inositol 1,4,5
      trisphosphate 3-kinase C (ITPKC) gene rs28493229 was recently found to be
      associated with the risk for KD in the Japanese population, suggesting that the
      ITPKC gene may contribute to KD susceptibility. This study investigated the
      association of ITPKC polymorphisms with KD in a Han Chinese population. Five
      ITPKC Single-nucleotide polymorphisms, including rs28493229, were genotyped in
      223 unrelated patients who had KD and 318 non-KD control subjects. The allele,
      genotype, and haplotype frequencies were compared between the patients and the
      control subjects, between the patients with and those without CALs, and between
      patients resistant to intravenous immunoglobulin treatment and those responsive
      to such treatment. Multiple alleles were observed for rs28493229 and rs2290692.
      No significant differences in the frequencies of the C allele, the CC genotype,
      or the C carriers of rs28493229 were observed in the comparisons. Interestingly,
      significantly higher frequencies of the C allele (p < 0.001), the CC genotype (p
      = 0.001), and the C carriers (p = 0.003) were observed for rs2290692 among the
      patients than among the control subjects, and similar differences were observed
      between the patients with and those without CALs. The GC haplotype for rs28493229
      and rs2290692 was more common among the patients than among the control subjects.
      The results indicate that the C allele of the ITPKC gene rs2290692 is linked to a
      significantly higher risk for KD in the studied population, which provides new
      evidence to support the importance of the ITPKC gene in the occurrence of KD.
      More notably, this finding suggests that there may be an unidentified ITPKC
      polymorphism in strong linkage disequilibrium to rs2290692, significantly
      affecting susceptibility to KD in the Han population.

PMID- 22361741
TI  - Pressure overload leads to an increase of cardiac resident stem cells.
AB  - Recent studies suggest that the mammalian heart possesses some capacity for
      cardiac regeneration. This regenerative capacity is primarily documented
      postnatally and after myocardial infarction or pressure overload. Although the
      cell type that mediates endogenous regeneration is unclear, cardiac stem cells
      might be considered as potential candidates. To determine the number of c-kit +
      cardiac resident cells under conditions of pressure overload, we evaluated
      specimens derived from n = 8 patients with pressure overloaded single right
      ventricles in comparison to n = 4 explanted hearts from patients with dilated
      cardiomyopathy and n = 14 biopsies from children after heart transplantation. The
      age of the patients ranged from 16 days to 19 years. For quantification of
      cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and
      expressed as percent of the total nuclei. In specimens from patients with dilated
      cardiomyopathy, 0.13 +/- 0.09% c-kit +/mast cell tryptase-/CD45- cells were
      detected. However, in specimens from patients with pressure overloaded single
      right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were
      significantly higher (0.41 +/-0.24%, p < 0.05). Under conditions of pressure
      overload, the right ventricle shows an approximately three-fold increase in c
      kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this
      increased number of c-kit+ cells is not sufficient to prevent the failing heart
      from congestive heart failure, understanding the mechanism that leads to an
      increase of presumably cardiac resident stem cells under conditions of pressure
      overload might help to develop new strategies to enhance endogenous repair.

PMID- 22361742
TI  - Left atrium of the human adult heart contains a population of side population
      cells.
AB  - Cardiac "side population" (SP) cells have previously been found to differentiate
      into both endothelial cells and cardiomyocytes in mice and rats, but there are no
      data on SP cells in the human adult heart. Therefore, human cardiac atrial
      biopsies were dissociated, stained for SP cells and analyzed with FACS.
      Identified cell populations were analyzed for gene expression by quantitative
      real-time PCR and subjected to in vitro differentiation. Only biopsies from the
      left atrium contained a clearly distinguishable population of SP cells (0.22 +/-
      0.08%). The SP population was reduced by co-incubation with MDR1 inhibitor
      Verapamil, while the ABCG2 inhibitor FTC failed to decrease the number of SP
      cells. When the gene expression was analyzed, SP cells were found to express
      significantly more MDR1 than non-SP cells. For ABCG2, there was no detectable
      difference. SP cells also expressed more of the stem cell-associated markers C
      KIT and OCT-4 than non-SP cells. On the other hand, no significant difference in
      the expression of endothelial and cardiac genes could be detected. SP cells were
      further subdivided based on CD45 expression. The CD45-SP population showed
      evidence of endothelial commitment at gene expression level. In conclusion, the
      results show that a SP population of cells is present also in the human adult
      heart.

PMID- 22361743
TI  - Modeling and optimization of poly(3hydroxybutyrate-co-3hydroxyvalerate)
      production from cane molasses by Azohydromonas lata MTCC 2311 in a stirred-tank
      reactor: effect of agitation and aeration regimes.
AB  - The effects of agitation and aeration rates on copolymer poly(3-hydroxybutyrate
      co-3-hydroxyvalerate) [P(3HB-co-3HV)] production by Azohydromonas lata MTCC 2311
      using cane molasses supplemented with propionic acid in a bioreactor were
      investigated. The experiments were conducted in a three-level factorial design by
      varying the impeller (150-500 rev min(-1)) and aeration (0.5-1.5 vvm) rates.
      Further, the data were fitted to mathematical models [quadratic polynomial
      equation and artificial neural network (ANN)] and process variables were
      optimized by genetic algorithm-coupled models. ANN and hybrid ANN-GA were found
      superior for modeling and optimization of process variables, respectively. The
      maximum copolymer concentration of 7.45 g l(-1) with 21.50 mol% of 3HV was
      predicted at process variables: agitation speed, 287 rev min(-1); and aeration
      rate, 0.85 vvm, which upon validation gave 7.20 g l(-1) of P(3HB-co-3HV) with 21
      mol% of 3HV with the prediction error (%) of 3.38 and 2.32, respectively.
      Agitation speed established a relative high importance of 72.19% than of aeration
      rate (27.80%) for copolymer accumulation. The volumetric gas-liquid mass transfer
      coefficient (k (L) a) was strongly affected by agitation and aeration rates. The
      highest P(3HB-co-3HV) productivity of 0.163 g l(-1) h(-1) was achieved at 0.17 s(
      1) of k (L) a value. During the early phase of copolymer production process, 3HB
      monomers were accumulated, which were shifted to 3HV units (9-21%) during the
      cultivation period of 24-42 h. The enhancement of 7.5 and 34% were reported for
      P(3HB-co-3HV) production and 3HV content, respectively, by hybrid ANN-GA
      paradigm, which revealed the significant utilization of cane molasses for
      improved copolymer production.

PMID- 22361744
TI  - New and emerging treatments for advanced prostate cancer.
AB  - Historically, the treatment of metastatic castration-resistant prostate cancer
      (CRPC) has been limited to chemotherapeutic regimens that did not improve patient
      survival. In 2004, clinical studies began to demonstrate significant improvements
      in patient outcomes, including overall survival, with docetaxel versus
      mitoxantrone chemotherapy. Since these pivotal trials, the combination of
      docetaxel plus prednisone has become a standard of care for patients with
      metastatic CRPC. However, the limited survival benefit achieved with this regimen
      prompted several investigations into the development of alternative therapeutic
      options. Recent advances have now led to an unprecedented number of new drug
      approvals within the past year, providing many new treatment options for patients
      with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer
      treatment, is the first such immunotherapeutic agent approved by the US Food and
      Drug Administration. Other successes include abiraterone acetate, the first
      androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor,
      both of which have demonstrated improved survival following docetaxel failure.
      The bone-targeting agent denosumab, also recently approved in this setting,
      offers these patients significant improvement in the prevention of skeletal
      related events. The data supporting the approval of each of these agents are
      described in this monograph, as are current approaches in the treatment of
      metastatic CRPC and ongoing clinical trials of novel treatments and strategies.
      The experts also discuss several of the issues regarding the introduction of
      these novel agents into clinical practice for metastatic CRPC patients.

PMID- 22361745
TI  - Costs and quality of life for psoriatic patients at different degrees of severity
      in southern Sweden - a cross-sectional study.
AB  - OBJECTIVES: Knowledge of the societal costs of psoriasis is limited. This study
      estimated the cost of care, psoriasis area and severity index (PASI), and quality
      of life in a defined patient population in Sweden. METHODS: A prevalence-based
      prospective recruitment of patients visiting two Swedish dermatology clinics
      between September and December 2009 was performed, collecting resource
      utilization for health care contacts, treatment, travelling, and productivity
      loss during 1 month. RESULTS: 164 patients were included. Mean total cost per
      patient-month was 994?. Main cost drivers were outpatient visits and light
      therapy (49%), biological drugs (20%) and productivity loss (22%). Total cost for
      topical treatment only (TT; 34%) was 369?, light therapy (LT; 24%) 1,274?,
      traditional systemic treatment (TST; 26%) 1,085? and biological systemic
      treatment (BST; 16%) 1,709? per patient-month. Main cost drivers were: outpatient
      visits (56%) in TT as well as for LT (78%), productivity loss (40%) in TST, and
      biological drugs (71%) among BST patients. There was no clear relationship
      between clinical (PASI) or subjective (DLQI) severity estimations and costs.
      CONCLUSIONS: The one-month cost-of-illness amounted to almost 1,000?/month, with
      great variations. Despite 1,190? difference in drug cost for TST vs BST, total
      cost per month differed by 623? because of offsets from improved productivity. A
      trend towards lower severity and reductions in outpatient and topical treatment
      costs was seen.

PMID- 22361746
TI  - Metastatic spinal cord compression in non-small cell lung cancer patients.
      Prognostic factors in a series of 356 patients.
AB  - BACKGROUND: Patients with metastatic spinal cord compression (MSCC) from non
      small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most
      other MSCC patients. This study was performed to identify prognostic factors for
      functional outcome and survival in these patients after radiotherapy (RT) alone.
      PATIENTS AND METHODS: Data of 356 patients irradiated for MSCC from NSCLC were
      retrospectively analyzed. Ten potential prognostic factors were investigated
      including age, gender, Eastern cooperative Oncology Group performance score (ECOG
      PS), number of involved vertebrae, pre-RT ambulatory status, other bone
      metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC,
      time developing motor deficits before RT, and the radiation schedule. RESULTS: On
      multivariate analysis, better functional outcome was associated with pre-RT
      ambulatory status (estimate: - 0.84, p = 0.022), no visceral metastases
      (estimate: - 1.15, p < 0.001), interval from cancer diagnosis to RT of > 15
      months (estimate:  + 0.48, p = 0.019), and slower (> 7 days) development of motor
      deficits (estimate:  + 1.56, p < 0.001). On multivariate analysis, improved
      survival was significantly associated with female gender (risk ratio (RR) 1.32, p
      = 0.043), ECOG-PS 1-2 (RR 1.45, p = 0.034), pre-RT ambulatory status (RR 0.58, p
      < 0.001), no other bone metastases (RR 1.38, p = 0.010), no visceral metastases
      (RR 2.87, p < 0.001), interval from cancer diagnosis to RT of > 15 months (RR
      0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p
      < 0.001). CONCLUSION: This study identified additional independent prognostic
      factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic
      factors can be used for stratification in future trials and can help develop
      prognostic scores for MSCC from NSCLC.

PMID- 22361747
TI  - Dysregulated TLR3-dependent signaling and innate immune activation in superoxide
      deficient macrophages from nonobese diabetic mice.
AB  - In type 1 diabetes (T1D), reactive oxygen species (ROS) and proinflammatory
      cytokines produced by macrophages and other innate immune cells destroy
      pancreatic beta cells while promoting autoreactive T cell maturation. Superoxide
      deficient nonobese diabetic mice (NOD.Ncf1(m1J)) are resistant to spontaneous
      diabetes, revealing the integral role of ROS signaling in T1D. Here, we evaluate
      the innate immune activation state of bone marrow-derived macrophages (BM-Mphi)
      from NOD and NOD.Ncf1(m1J) mice after poly(I:C)-induced Toll-like receptor 3
      (TLR3) signaling. We show that ROS synthesis is required for efficient activation
      of the NF-kappaB signaling pathway and concomitant expression of TLR3 and the
      cognate adaptor molecule, TRIF. Poly(I:C)-stimulated NOD.Ncf1(m1J) BM-Mphi
      exhibited a 2- and 10-fold decrease in TNF-alpha and IFN-beta proinflammatory
      cytokine synthesis, respectively, in contrast to NOD BM-Mphi. Optimal expression
      of IFN-alpha/beta is not solely dependent on superoxide synthesis, but requires
      p47(phox) to function in a NOX-independent manner to mediate type I interferon
      synthesis. Interestingly, MHC-II I-A(g7) expression necessary for CD4 T cell
      activation is increased 2-fold relative to NOD, implicating a role for superoxide
      in I-A(g7) downregulation. These findings suggest that defective innate immune
      pattern-recognition receptor activation and subsequent decrease in TNF-alpha and
      IFN-beta proinflammatory cytokine synthesis necessary for autoreactive T cell
      maturation may contribute to the T1D protection observed in NOD.Ncf1(m1J) mice.

PMID- 22361748
TI  - Occludin is required for apoptosis when claudin-claudin interactions are
      disrupted.
AB  - Disruption of tight junctions is often seen during pathogen infection,
      inflammation, and tumor progression. Mislocalization of the tight junction
      proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis
      through the extrinsic pathway. To further investigate the mechanism of this
      response, a normal mammary epithelial cell line (EpH4) as well as primary mammary
      epithelial cells were treated with a claudin-disrupting mimic peptide, DFYNP
      (aspartic acid-phenylalanine-tyrosine-asparagine-proline). Using fluorescent
      indicators, we found that caspase-3 activation, resulting from treatment with
      DFYNP, was restricted to EpH4 and primary mammary epithelial cells with
      mislocalized claudin-4. Mislocalized claudin-4 and occludin were colocalized in
      non-junctional puncta, and both molecules were found in the death-inducing
      signaling complex (DISC) where they colocalized with Fas, fas-associated protein
      with death domain (FADD), active caspase-8 and caspase-3 at distinct apical
      domains. Importantly, caspase-3 activation was totally repressed in primary
      mammary epithelial cells from occludin null mice. Thus, the apoptotic response
      appears to be initiated by the movement of occludin to the DISC suggesting that
      this molecule has signaling properties that initiate cell death when its tight
      junction location is disrupted.

PMID- 22361749
TI  - Structural characterization of carangid fish myoglobins.
AB  - The primary structures of myoglobin (Mb) from the following five carangid species
      were determined: yellowtail Seriola quinqueradiata, greater amberjack Seriola
      dumerili, yellowtail kingfish Seriola lalandi, Japanese horse mackerel Trachurus
      japonicus, and silver trevally Pseudocaranx dentex. The sequences were of varying
      composition both in the coding and in the noncoding regions, but all contained
      the open reading frame of 444 nucleotides encoding 147 amino acids. Amino acid
      sequence identities of carangid Mbs were in the range of 81-99%. The similarity
      of the heme pocket and associated heme-binding residues of carangid Mbs were
      evidence of the conservative nature of Mbs. Similar to the other teleost Mbs,
      carangid Mbs did not contain a D helix and had mostly conserved A and E helices
      as well as E-F and G-H inter-helical segments. Hydropathy profiles of carangid
      Mbs showed species-specific variations where silver trevally Mb exhibited
      generally higher hydrophobicity. Phylogenetic analysis based on the primary
      structures was in agreement with conventional morphological taxonomy,
      establishing close proximity of carangid Mbs with those of cichlid and scombroid,
      the other members of the Perciformes order.

PMID- 22361750
TI  - Effect of veratric acid on the cardiovascular risk of L-NAME-induced hypertensive
      rats.
AB  - Hypertension is associated with dyslipidemia, which is a significant risk factor
      for cardiovascular complications. This study was undertaken to investigate the
      effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile
      in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats.
      Hypertension was induced in adult male albino rats of Wistar strain, weighing 180
      220 g, by oral administration of L-NAME (40 mg/kg) in drinking water for 4 weeks.
      Rats were treated with VA (40 mg/kg) for 4 weeks. L-NAME-treated rats showed
      significant increase in mean arterial pressure and heart rate. A significant
      increase in the concentrations of plasma, tissue (liver and kidney) lipids, and
      lipoproteins and a significant decrease in the concentration of high-density
      lipoprotein cholesterol were noticed in L-NAME-induced hypertensive rats. The
      activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase increased
      significantly in the liver and kidney, whereas the activities of lipoprotein
      lipase and lecithin cholesterol acyl transferase were decreased significantly in
      the plasma of hypertensive rats. Histopathology of liver and kidney and in vitro
      study also confirmed the biochemical findings of this study. Thus, oral
      administration of VA reduced hyperlipidemia related to the risk of hypertension.

PMID- 22361751
TI  - Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve
      activity in patients with acute myocardial infarction and type 2 diabetes
      mellitus.
AB  - Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal
      myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the
      mechanisms of such favorable effects remain speculative. The aim of this study
      was to investigate the effect of pioglitazone on arterial baroreflex sensitivity
      (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent
      MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and
      those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS,
      MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA
      IR), and plasma adiponectin were measured at baseline and after 12 weeks.
      Pioglitazone increased plasma adiponectin (from 6.9 +/- 3.3 MUg/dL to 12.2 +/-
      7.1 MUg/dL) and reduced HOMA-IR (from 4.0 +/- 2.2 to 2.1 +/- 0.9). In the
      pioglitazone group, MSNA decreased significantly (from 37 +/- 7 bursts/min to 25
      +/- 8 bursts/min) and BRS increased significantly (from 6.7 +/- 3.0 to 9.9 +/-
      3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found
      between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone
      decreased the sympathetic nerve traffic through the improvement of insulin
      resistance in DM patients with recent MI, which indicate that the
      sympathoinhibitory effects of pioglitazone may, at least in part, have
      contributed to the beneficial effects of pioglitazone.

PMID- 22361752
TI  - Are clinical microbiology laboratories missing out quality control and quality
      assurance in laboratory management?

PMID- 22361753
TI  - Anaerobic microbiology: time to rejuvenate.

PMID- 22361754
TI  - Human immunodeficiency virus type-2-A milder, kinder virus: an update.
AB  - Human immunodeficiency virus type-2 (HIV-2) belongs to the family retroviridae
      which is phylogenetically clusters with SIV SM from sooty mangabeys. This virus
      is morphologically similar to human immunodeficiency virus type-1 (HIV-1) but has
      got only a 40% homology at the nucleotide level. There is a distinct geographical
      distribution of HIV-2 unlike HIV-1. There are currently eight subtypes/groups
      identified with subtype/group A responsible for the majority of infections. HIV-2
      shows a considerable difference in the course of the disease. Clinical,
      haematological and immunological evaluation of individuals infected with HIV-2
      has shown the virus to be less pathogenic than HIV-1 although the exact mechanism
      underlying this difference is not well defined. Similar to HIV-1, the HIV-2
      isolates also showed distinct replicative and cytopathic characteristics. The
      transmission rate for HIV-2 compared to HIV-1 is very low both by heterosexual
      route and mother to child transmission. The clinical signs and symptoms of
      immunodeficiency associated with HIV-2 are similar to the ones seen among the HIV
      1-infected individuals and they can also progress to AIDS. It is naturally
      resistant to NNRTI and hence the diagnosis become important as it affects the
      treatment strategy. Similar to HIV-1, HIV-2 strains of infected individuals also
      show mutations that can cause drug resistance. The current evidence suggests that
      there is no protective effective for HIV-2 against HIV-1.

PMID- 22361755
TI  - Typing of Methicillin resistant Staphylococcus aureus: a technical review.
AB  - Increasing prevalence of Methicillin-resistant Staphylococcus aureus (MRSA)
      worldwide is a growing public health concern. MRSA typing is an essential
      component of an effective surveillance system to describe epidemiological trends
      and infection control strategies. Current challenges for MRSA typing are focused
      on selecting the most appropriate technique in terms of efficiency, reliability,
      ease of performance and cost involved. This review summarises the available
      information on application, potential and problems of various typing techniques
      in discriminating the strains and understanding the epidemiology of MRSA strains.
      The phenotypic methods in general are easier to perform, easier to interpret,
      cost effective and are widely available, however less discriminatory. The
      genotypic methods are expensive and technically demanding, however more
      discriminatory. Newer technologies involving sequencing of various genes are
      coming up as broadly applicable and high throughput typing systems. Still there
      is no consensus regarding the single best method for typing of MRSA strains.
      Phage typing is recommended as first line approach in epidemiological
      investigation of MRSA strains. PFGE remains the gold standard for
      characterisation of outbreak strains. DNA sequencing methods including MLST, spa
      typing, SCCmec typing and toxin gene profile typing are more practical methods
      for detecting evolutionary changes and transmission events. The choice of typing
      technique further depends on the purpose of the study, the facilities available
      and the utility of data generated to answer a desirable research question. A need
      for harmonisation of typing techniques by following standard protocols is
      emphasised to establish surveillance networks and facilitate global MRSA control.

PMID- 22361756
TI  - Comparison of primers for the detection of genogroup II noroviruses in India.
AB  - PURPOSE: Noroviruses (NoV) are increasingly recognized as an important cause for
      acute gastroenteritis, worldwide. Reverse transcription polymerase chain reaction
      (RT-PCR) and sequencing are the methods of choice for the detection of NoVs, but
      there is currently no consensus about the primers to be used in these assays.
      MATERIALS AND METHODS: In this study, five published primer sets were evaluated
      for the detection of genogroup II (GII) NoVs in India. The primers target
      different regions of the NoV genome. Three primer sets detect an NoV in a single
      round RT-PCR platform, while the remaining two primer sets are based on a nested
      RT-PCR platform. RESULT: A panel of 100 samples from previous studies on
      norovirus diarrhoea in children were tested by all five primer sets. Of them, 74
      samples were identified as positive for NoV, by at least one primer set. Subsets
      of positive amplicons were sequenced to check for specificity. CONCLUSION: The
      most sensitive primer set was Girish 2002, which detected GII NoV by nested RT
      PCR, and was modified from the previously published primers. This study
      demonstrates that higher detection can be obtained by either using multiple
      primer sets or using a sensitive nested RT-PCR assay. It also demonstrates the
      differences in primer sensitivity for detection of Genogroup II (GII) NoVs in
      India.

PMID- 22361757
TI  - Rationale of azithromycin prescribing practices for enteric fever in India.
AB  - PURPOSE: The present study was performed to assess the current susceptibility
      pattern of blood isolates of Salmonella spp from a super specialty hospital in
      North India against nalidixic acid, ciprofloxacin and azithromycin and compare
      the in vitro and in vivo response against azithromycin. MATERIALS AND METHODS: We
      evaluated the minimum inhibitory concentration's (MIC's) of 107 blood isolates of
      Salmonella spp against nalidixic acid, azithromycin and ciprofloxacin and
      correlated in vitro and in vivo response of azithromycin from the treatment and
      discharge summaries from the Hospital Information System (HIS) software. RESULTS:
      Among the 107 isolates evaluated, 94 (87.8%) were nalidixic acid-resistant (NAR)
      Salmonella and 36 were resistant to azithromycin by MIC testing. The MIC 90 value
      for azithromycin was 24 MUg/mL. Among the 57 treatment histories evaluated using
      the HIS software, 19 (33%) patients had documented clinical non-response to
      azithromycin which required change of therapy. CONCLUSIONS: The present study
      observed a higher MIC 90 values for azithromycin compared to Salmonella isolates
      from Western studies. There was also a documented clinical non-response against
      azithromycin. The in vitro and in vivo findings in this study suggest a guarded
      use of azithromycin for cases of enteric fever in India. The study also augments
      the reversal of resistance pattern in favour of chloramphenicol, ampicillin and
      trimethoprim - sulfamethoxazole.

PMID- 22361758
TI  - In vitro pharmacodynamic properties of colistin methanesulfonate and amikacin
      against Pseudomonas aeruginosa.
AB  - PURPOSE: In vitro pharmacodynamic properties of colistin methanesulfonate and
      amikacin were investigated by studying time-kill kinetics and post-antibiotic
      effect (PAE) against strains of Pseudomonas aeruginosa isolated from patients
      with cystic fibrosis. METHOD: Synergy was investigated at 0.5 *, 1 * and 5 * MIC
      of antibiotics using time-kill curve method. PAEs were determined by the standard
      viable counting method where bacteria in the logarithmic phase of growth were
      exposed for 1 h to the antibiotics at 1 * or 20 * MIC, alone and in combinations.
      Synergy and additive effects were detected at 1 * MIC, at 24 h. RESULTS: Some of
      the strains produced an earlier synergistic effect at 12 h. No antagonism was
      observed. Colistin methanesulfonate and amikacin produced PAEs 1.16 +/- 0.10 to
      2.25 +/- 0.16 h and 0.96 +/- 0.15 to 2.69 +/- 0.32 h, respectively. When the
      antibiotics were used in combination the PAEs were prolonged to a value of 3.88
      +/- 0.25 h. Consequently, the CONCLUSIONS: Findings of this study may play useful
      role in selecting the appropriate combinations when a single agent is inadequate,
      and may have important information for optimizing the dose intervals.

PMID- 22361759
TI  - A rapid and reliable species-specific identification of clinical and
      environmental isolates of Vibrio cholerae using a three-test procedure and recA
      polymerase chain reaction.
AB  - PURPOSE: Vibrio cholerae, the cause of cholera, is one of the leading causes of
      morbidity and mortality in many developing countries. Most laboratories initially
      rely on biochemical tests for a presumptive identification of these strains,
      followed by a polymerase chain reaction (PCR)-based method to confirm their
      identification. The aim of this study is to establish a rapid and reliable
      identification scheme for V. cholerae using a minimal, but highly specific number
      of biochemical tests and a PCR assay. MATERIALS AND METHODS: We developed a
      species-specific PCR to identify V. cholerae, using a housekeeping gene recA, and
      used that to evaluate the sensitivity and specificity of 12 biochemical tests
      commonly used for screening and / or presumptive identification of V. cholerae in
      the clinical and environmental samples. RESULTS: Here we introduced a combination
      of three biochemical tests, namely, sucrose fermentation, oxidase test, and
      growth in trypton broth containing 0% NaCl, as also the PCR of the recA gene, for
      rapid identification of V. cholerae isolates, with 100% sensitivity and
      specificity. The established method accurately identified a collection of 47 V.
      cholerae strains isolated from the clinical cases (n = 26) and surface waters (n
      = 21), while none of the 32 control strains belonging to different species were
      positive in this assay. CONCLUSION: The triple-test procedure introduced here is
      a simple and useful assay which can be adopted in cholera surveillance programs
      for efficient monitoring of V. cholerae in surface water and fecal samples.

PMID- 22361760
TI  - Prevalence and antimicrobial resistance pattern of multidrug-resistant
      enterococci isolated from clinical specimens.
AB  - PURPOSE: Vancomycin-resistant enterococci (VRE) pose an emerging problem in
      hospitals worldwide. The present study was undertaken to determine the
      occurrence, species prevalence, antibacterial resistance, and phenotypic and
      genetic characteristics of VRE isolated in Riyadh hospitals, KSA. MATERIALS AND
      METHODS: Two hundred and six isolates of enterococcal species were obtained from
      clinical samples. The antibiotic susceptibility of isolates and minimum
      inhibitory concentration (MIC) tests for vancomycin and teicoplanin were
      determined. Molecular typing of VRE isolates was carried out by using pulsed
      field gel electrophoresis (PFGE) and the resistance genotype was determined by
      polymerase chain reaction (PCR). RESULTS: VRE accounted for 3.9% of the isolates
      and were detected mostly in urine, wound and blood specimens isolated from ICU,
      internal medicine and surgical wards. All strains were identified to species
      level and were found to consist of E. faecalis (69.2%), E. faecium (11.3%), E.
      avium (2.1%), E. hirae (0.8%), E. casseliflavus (1.3%) and E. gallinarum (1.3%)
      species. According to the susceptibility data obtained, 8 (3.9%) out of 206
      isolates were found to be VRE (MICs > 32 MUg/ml). The vanA, vanB and vanC gene
      fragments of E. faecalis, E. faecium and E. gallinarum were amplified from
      isolates and were detected. PFGE patterns of the VRE isolates revealed homogenous
      patterns with dominant clone suggesting that the strains intrinsic resistance is
      independent. CONCLUSIONS: This study shows an emergence of VRE along with
      increased rate of multidrug-resistant enterococci in the area of the study.
      Regular surveillance of antimicrobial susceptibilities should be done regularly
      and the risk factors should be determined.

PMID- 22361761
TI  - Isolation, speciation, and antibiogram of clinically relevant non-diphtherial
      Corynebacteria (Diphtheroids).
AB  - PURPOSE: Coryneform or the non-diphtherial Corynebacterium species largely
      remains a neglected group with the traditional consideration of these organisms
      as contaminants. This concept, however, is slowly changing in the light of recent
      observations. This study has been done to find out the species distribution and
      antibiogram of various members of the clinically relevant Coryneform group,
      isolated from various clinical materials. MATERIALS AND METHODS: One hundred and
      fourteen non-duplicate isolates of diphtheroids from various clinical isolates
      were selected for the study. The isolates were identified to the species level by
      using a battery of tests; and antimicrobial susceptibility was tested by using a
      combination of Clinical and Laboratory Standards Institute (CLSI) and the British
      Society for Antimicrobial Chemotherapy (BSAC) guidelines, in the absence of
      definitive CLSI guidelines. RESULTS: Corynebacterium amycolatum was the
      predominant species (35.9%) in our series followed by the CDC Group G organisms
      (15.7%). Each of the remaining 19 species comprised of less than 10% of the
      isolates. More than half the total isolates were resistant to the penicillins,
      erythromycin, and clindamycin; while excellent activity (all the strains being
      susceptible) was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol
      and tetracycline also had good activity in inhibiting more than 80% of the
      isolates. Multiply drug resistance was exhibited by all the species. CONCLUSION:
      This study was an attempt to establish the clinical significance of coryneform
      organisms. The high level of resistance shown by this group to some of the common
      antibacterial agents highlights the importance of processing these isolates in
      select conditions to guide the clinicians towards an appropriate therapy.

PMID- 22361762
TI  - Utility of GenoType MTBDRplus assay in rapid diagnosis of multidrug resistant
      tuberculosis at a tertiary care centre in India.
AB  - PURPOSE: Molecular methods which allow rapid detection of tuberculosis as well as
      drug resistance directly from clinical samples have become the most popular
      diagnostic methodology with the emergence of multidrug resistant tuberculosis.
      The aim of the present study was to evaluate the performance of a line probe
      assay, GenoType MTBDRplus for the rapid detection of Mycobacterium tuberculosis
      and mutations causing rifampicin and INH resistance directly in smear positive
      pulmonary specimens and also in M. tuberculosis isolates grown from various
      clinical specimens. MATERIALS AND METHODS: The MTBDRplus assay was done directly
      on 37 smear positive pulmonary specimens and also on 69 M. tuberculosis isolates
      obtained by rapid automated culture using Bact/Alert 3D. The results were
      compared with phenotypic drug susceptibility testing (1% proportion method) using
      Bact/Alert 3D. RESULTS: The sensitivity and specificity for detection of
      resistance to rifampicin was 100% and 97.3%, and to INH was 91.9% and 98.4%,
      respectively, in comparison with the phenotypic drug susceptibility testing.
      CONCLUSION: MTBDRplus assay had good sensitivity and specificity with turn around
      time of less than 48 hours. It may be a useful tool for rapid detection of
      multidrug resistant tuberculosis at a tertiary care centre.

PMID- 22361763
TI  - Evaluation of the microscopic observational drug susceptibility assay for rapid
      and efficient diagnosis of multi-drug resistant tuberculosis.
AB  - PURPOSE: Tuberculosis (TB) is endemic in India and the burden of multi-drug
      resistant tuberculosis (MDR-TB) is high. Early detection of MDR-TB is of primary
      importance in controlling the spread of TB. The microscopic observational drug
      susceptibility (MODS) assay has been described as a cost-effective and rapid
      method by which mycobacterial culture and the drug susceptibility test (DST) can
      be done at the same time. MATERIALS AND METHODS: A total of 302 consecutive
      sputum samples that were received in an accredited mycobacteriology laboratory
      for conventional culture and DST were evaluated by the MODS assay. RESULTS: In
      comparison with conventional culture on Lowenstein Jensen (LJ) media, the MODS
      assay showed a sensitivity of 94.12% and a specificity of 89.39% and its
      concordance with the DST by the proportion method on LJ media to isoniazid and
      rifampicin was 90.8% and 91.5%, respectively. The turnaround time for results by
      MODS was 9 days compared to 21 days by culture on LJ media and an additional 42
      days for DST by the 1% proportion method. The cost of performing a single MODS
      assay was Rs. 250/-, compared to Rs. 950/- for culture and 1st line DST on LJ.
      CONCLUSION: MODS was found to be a sensitive and rapid alternative method for
      performing culture and DST to identify MDR-TB in resource poor settings.

PMID- 22361764
TI  - Prevention of healthcare-associated infections in general practice: current
      practice and drivers for change in a French study.
AB  - PURPOSE: The fight against Healthcare-associated infections is a public health
      priority and a major challenge for the safety and quality of care. The objective
      was to assess hygiene in general practitioners' (GPs') office and identify
      barriers to and drivers for better practice. MATERIALS AND METHODS: We performed
      a cross-sectional study in which a questionnaire was sent to a randomly selected,
      representative sample of 800 GPs. We used a self-administered questionnaire. The
      first part assessed current practice and the second part focused on barriers and
      motivating factors for better practice. We performed a descriptive statistical
      analysis of the responses to closed questions and a qualitative analysis of the
      responses to open-ended questions. RESULTS: Only a third of the GPs were aware of
      the current guidelines. Disposable equipment was used by 31% of the GPs. For the
      remainder, only 38% complied with the recommended procedures for sterilisation or
      disinfection. Seventy-two percent of the GPs washed their hands between
      consultations in the office. A significant minority of physicians disregarded the
      guidelines by never wearing gloves to perform sutures (11%), treat wounds (10%),
      fit intrauterine devices (18%) or perform injections (18%). The main barriers to
      good practice were the high cost of modifications and lack of time/space. Two
      third of the GPs did not intend to change their practices. The drivers for change
      were pressure from patients (4.8 on a scale of 1 to 7), inspection by the health
      authorities (4.8) and the fear of legal action (4.4). CONCLUSIONS: Our results
      show that there are significant differences between current practice and laid
      down professional guidelines. Policies for improvement of hygiene must take into
      account barriers and motivating factors.

PMID- 22361765
TI  - Antimicrobial activities against biofilm formed by Proteus mirabilis isolates
      from wound and urinary tract infections.
AB  - BACKGROUND: Bacterial species are capable of living as biofilm and/or planktonic
      forms. There is increasing evidence for the role of bacterial biofilm in various
      wound and urinary tract infections (UTIs). The aim of the present study was to
      evaluate the ability of the bacteria, isolated from urinary tract infections
      (UTIs) and wound infections, to form biofilm and correlate the role of biofilm
      with their antimicrobial resistance. MATERIALS AND METHODS: All the isolated
      bacteria were screened for their ability to form biofilm using the microtitre
      plate method. RESULTS: Wound isolates of Staphylococcus aureus and Enterobacter
      sp. had more biofilm forming capacity than the UTI isolates. Proteus mirabilis
      isolates were among the strongest biofilm forming bacteria and were chosen for
      antimicrobial study. In sub-MIC concentrations of antimicrobial agents used,
      ciprofloxacin was found to be the most effective in decreasing biofilm formation.
      On the other hand, ceftriaxone and ciprofloxacin were effective in partial
      removal of preformed biofilm biomass. CONCLUSION: Ciprofloxacin was more
      effective in killing bacterial cells especially at high antimicrobial
      concentrations that could be reached in urine levels and can be used in
      impregenating catheters.

PMID- 22361766
TI  - Comparison of the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide
      tube method with the conventional method and real-time polymerase chain reaction
      for the detection of rifampicin resistance in Mycobacterium tuberculosis.
AB  - Colorimetric methods are cheap, reproducible, and rapid methods of detecting drug
      resistance in Mycobacterium tuberculosis. The MTT (3-(4,5-dimethylthiazole-2-yl)
      2,5-diphenyltetrazolium bromide) method is one such technique that has been
      established in our laboratory to detect rifampicin resistance. The present study
      compared the results of the MTT method with those of the proportion method and
      real-time polymerase chain reaction (RTPCR) in order to establish sensitivity and
      specificity of MTT. The mutations for rifampicin resistance occur in rpoB gene,
      and the commonest reported are in codons 526 and 531. Therefore, RTPCR was
      targeted at these two codons. The concordance of MTT with the proportion method
      and RTPCR was 94 and 72.77%, respectively, and that of RTPCR with the proportion
      method was 77.77%. While the study confirmed that the MTT method is a good method
      for detecting rifampicin resistance, it also brought out the fact that RTPCR when
      targeted for limited mutations is not a good tool. Either the genotypic method
      used should target the total 81-bp rpoB genome or methods such as DNA sequencing
      should be used. For resource-constraint laboratories, the MTT method can be
      considered as a better choice.

PMID- 22361767
TI  - Detection and species identification of Campylobacter in stool samples of
      children and animals from Vellore, south India.
AB  - Campylobacter spp. are an important cause of bacterial gastroenteritis frequently
      isolated from animal, poultry and environmental samples. In this study, we
      investigated the zoonotic potential of Campylobacter spp. by comparing prevalence
      rates and species in 394 children with diarrhoea and 652 animals in Vellore using
      PCR-based tools. Eighteen children (4.5%) had campylobacteriosis, a majority of
      whom had co-pathogens (15/18) and most were infected with Campylobacter jejuni
      (16/18). A few C. coli and mixed infections with both species were also seen.
      Among the animal samples, 16/25 chicken samples (64%) were positive and all were
      found to be C. jejuni.

PMID- 22361768
TI  - Preliminary investigation of environmental prevalence of Clostridium difficile
      affecting inpatients in a north Indian hospital.
AB  - A preliminary study was conducted to see the prevalence of Clostridium difficile
      in patients and their environment in a tertiary care hospital. Seventy-nine fecal
      specimens from hospitalized patients, 176 swab samples from beds and 48 from
      hands of hospital personnel were investigated. Sixty-three patients received
      antibiotics and 14 proton pump inhibitors. Abdominal pain was observed in 16
      patients with fever in 15 of them. C. difficile culture was positive in 12.6%
      patients at initial sampling but none were toxin-positive. Eight patients
      developed diarrhea and five were both culture and toxin-positive. Fifty-one
      percent of bed swab samples and 62.5% of hand swab samples were culture positive.
      Similarly 8.5% of bed swab samples and 4.2% of hand swab samples were positive
      for toxins A and B. The environmental cross-infection between patients and
      carriage by hospital personnel are plausible sources of C. difficile infection
      and spread in our hospital.

PMID- 22361769
TI  - Carbapenem resistance among Escherichia coli and Klebsiella pneumoniae in a
      tertiary care hospital in south India.
AB  - Carbapenem resistance among clinical isolates of Enterobacteriaceae, especially
      Escherichia coli and Klebsiella pneumoniae, is largely conferred by metallo-beta
      lactamase (MBL). Fifty-one non repetitive isolates of carbapenem-resistant
      (Meropenem and Imipenem) E. coli and K. pneumoniae were studied to determine the
      molecular mechanism for resistance. Presence of blaNDM and blaVIM was determined
      by polymerase chain reaction (PCR) and DNA sequencing. blaNDM was detected from
      majority of carbapenem-resistant K. pneumoniae (75%) and E. coli (66.6%). Timely
      detection and appropriate and aggressive infection control measures are required
      to control the spread of these bacteria in healthcare settings.

PMID- 22361770
TI  - Pneumococcusuria: From bench to bedside.
AB  - The present study highlights six cases of pneumococcusuria during the time period
      of May 2008 to May 2010. All the patients had a co-existing predisposing factor
      with the isolation of Streptococcus pneumoniae in urine. Five of the six patients
      having signs and symptoms of urinary tract infections (UTI) were treated and
      cured of the same. It becomes essential to consider pneumococcal UTI in the
      presence of clinical signs and symptoms associated with urinary tract
      abnormalities like hydronephrosis and renal stones. S. pneumoniae may be regarded
      as an emerging pathogen in UTI. Precise microbiological diagnosis must correlate
      with the clinical signs and symptoms for the administration of appropriate
      antibiotic therapy.

PMID- 22361771
TI  - Primary inoculation tuberculosis following a vehicular accident.
AB  - Tuberculosis is considered as a 're emerging disease', because of its resurgence
      and increased incidence in the 21 st century particularly in immuno-compromised
      patients. About one fifth of diagnosed new cases of tuberculosis have an
      extrapulmonary lesion, of which about one-tenth involve the musculoskeletal
      system. Tuberculosis involving the soft tissue from adjacent bone or joint is
      well recognized but cutaneous tuberculous infection is rare, accounting for 0.1%
      of all cases seen in a dermatology service. We report a case of primary cutaneous
      tuberculosis of forearm following a vehicular accident in a young immunocompetent
      female.

PMID- 22361772
TI  - Isolated tubercular splenic abscess: can we defer splenectomy? Our single
      experience with anti-tuberculous therapy alone.
AB  - Isolated splenic tuberculosis is an exceedingly rare clinical condition.
      Microbiological confirmation of diagnosis in such cases is quite difficult. We
      encountered the case of a 35-year-old female, who presented with persistent low
      grade fever and weight loss. The CT scan of the abdomen revealed multiple
      hypodense splenic lesions. No primary focus of infection was detected in any
      other organs. Fine needle aspiration of splenic lesion revealed acid-fast bacilli
      on Ziehl-Neelsen stain. With anti-tuberculous therapy, the lesions regressed
      significantly in size. We stress that splenic tuberculosis should be considered
      as a diagnostic possibility even in immunocompetent individuals and choose
      combination antituberculous therapy as the first line treatment with
      consideration of splenectomy depending on response.

PMID- 22361773
TI  - Prolonged jaundice attributed to super infection of hepatitis E virus in a case
      of resolving leptospirosis.
AB  - India is endemic for both Leptospira and hepatitis E virus (HEV). The clinical
      presentations of these diseases have overlapping features. We report a case of
      superinfection of HEV in a patient with resolving leptospirosis with underlying
      Hodgkin lymphoma. The diagnosis of HEV in our case was established by HEV-RNA PCR
      as our patient was immunosuppressed. The present study highlights the need for
      molecular diagnosis in the case of HEV infection with strong clinical suspicion
      and negative serological results.

PMID- 22361774
TI  - An unusual case of non-disseminated bladder aspergillosis in a setting of
      transitional cell carcinoma.
AB  - A bladder infection of Aspergillus with no evidence of dissemination is rare. We
      present a case of Aspergillus infection with transitional cell carcinoma of the
      urinary bladder without any evidence of systemic involvement. A 65-year-old male
      diabetic whose main complaints were intermittent painful haematuria and nocturia
      had undergone nephroureterectomy a year and a half back for transitional cell
      carcinoma of right renal pelvis. Cystoscopy revealed bladder mucosa having fixed
      broad tumour with encrustation and bleeding on touch at the right vesico-ureteric
      junction. The histopathologic diagnosis was a high-grade transitional carcinoma
      with Aspergillus infection. Fungal culture of urine obtained after bladder wash
      yielded Aspergillus fumigatus.

PMID- 22361775
TI  - Rhinosporidiosis of the parotid duct presenting as a parotid duct cyst - a report
      of three cases.
AB  - Rhinosporidiosis is a chronic granulomatous infection caused by Rhinosporidium
      seeberi. Rhinosporidiosis has been reported from many countries but is endemic in
      certain parts of India and Sri Lanka. The common sites of involvement are the
      nose and nasopharynx followed by ocular tissue. Rhinosporidiosis is also known to
      involve many rare sites and may become disseminated to occur in a generalized
      form. Rhinosporidiosis of the parotid duct is rare and only five reported cases
      could be found in the literature. We report three cases of rhinosporidiosis of
      parotid duct presenting clinically as a parotid duct cyst. Rhinosporidiosis was
      diagnosed by histopathology. None of these patients had rhinosporidiosis at any
      other site.

PMID- 22361777
TI  - Serotype 19A Streptococcus pneumoniae among Indian isolates is a cause for
      concern.

PMID- 22361778
TI  - Suppurative sialadenitis in a neonate by methicillin-resistant Staphylococcus
      aureus: do we need search and kill superbug strategy?

PMID- 22361779
TI  - In vitro study to evaluate the sensitivity to daptomycin among gram positive
      clinical isolates.

PMID- 22361780
TI  - Pulsed laser triggered high speed microfluidic fluorescence activated cell
      sorter.
AB  - We report a high speed and high purity pulsed laser triggered fluorescence
      activated cell sorter (PLACS) with a sorting throughput up to 20,000 mammalian
      cells s(-1) with 37% sorting purity, 90% cell viability in enrichment mode, and
      >90% purity in high purity mode at 1500 cells s(-1) or 3000 beads s(-1). Fast
      switching (30 MUs) and a small perturbation volume (~90 pL) is achieved by a
      unique sorting mechanism in which explosive vapor bubbles are generated using
      focused laser pulses in a single layer microfluidic PDMS channel.

PMID- 22361781
TI  - Rules and scales used in measurement in the forensic setting: measured--and found
      wanting!

PMID- 22361782
TI  - Anthraquinone derivatives as electron-acceptors with liquid crystalline
      properties.
AB  - Dialkoxy derivatives of anthraquinone (AQ), dicyano-anthraquinone (DCAQ) and
      tetracyanoanthraquinone (TCAQ) were synthesized and their associated
      electrochemical, optical and self-assembling properties were investigated as
      candidates for n-type materials. AQ shows UV absorption features, whereas both
      DCAQ and TCAQ exhibit bathochromic and hyperchromic electronic transitions into
      the visible region. The electron accepting strength of the three compounds was
      established by cyclic voltammetry as -1.52 V, -1.3 V and -0.9 V vs.
      ferrocene/ferricenium for AQ, DCAQ and TCAQ, respectively. All three quinones
      displayed quasireversible, two sequential one-electron transfer redox reactions.
      DFT calculations of DCAQ and TCAQ demonstrate structural changes upon reduction,
      which is supported by spectroelectrochemical experiments. Furthermore, the
      structural changes result in different absorption profiles and show potential as
      electrochromic materials. Finally, both AQ and DCAQ show liquid crystalline
      phases and importantly, DCAQ exhibits both a smectic liquid crystalline and a
      soft crystal phase between -6  degrees C and 85  degrees C, which offers promise
      as a self-assembling n-type material.

PMID- 22361783
TI  - Copper perchlorate and tetrafluoridoborate compounds with the ligand 1,4,5
      triazanaphthalene. Gradual transformation of mononuclear Cu(II) compounds via
      polynuclear mixed-valence Cu(II)/Cu(I) species to dinuclear Cu(I); syntheses,
      characterizations and X-ray structures.
AB  - When the ligand 1,4,5-triazanaphthalene (abbreviated as tan) is reacted with
      Cu(II) BF(4)(-) and ClO(4)(-) salts, a variety of mononuclear compounds has been
      found, all with the [Cu(tan)(4)] unit and varying amounts of weakly coordinating
      axial ligands and lattice solvents. Reproducible compounds formed include two
      purple compounds, analyzing as [Cu(tan)(4)](ClO(4))(2)(CH(3)OH)(2)(H(2)O) (1) and
      [Cu(tan)(4)](BF(4))(2)(CH(3)OH)(1.5)(H(2)O) (3), and two blue compounds,
      analyzing as [Cu(tan)(4)](ClO(4))(2)(H(2)O)(2) (2) and
      [Cu(tan)(4)](2)(BF(4))(2)(H(2)O)(2) (4). Upon standing at room temperature, red
      coloured, mixed-valence dinuclear-based 3D coordination polymers are formed by
      conversion of the purple/blue products, of which [Cu(2)(tan)(4)](n)(BF(4))(3n)
      (5) and the isomorphic methanol-water adduct
      [Cu(tan)(4)](n)(BF(4))(3n)(CH(3)OH)(n)(H(2)O)(5n) (5A) are presented in this
      paper. In addition a fully reduced dinuclear Cu(I) compound of formula
      [Cu(2)(tan)(3)(ClO(4))(2)] (7) has been observed, and structurally characterized,
      as a rare three-blade propeller structure, with a Cu-Cu distance of 2.504 A.

PMID- 22361784
TI  - The relationship between symptomatology and treatment selection in metastatic
      castrate-resistant prostate cancer.
AB  - Metastatic castrate-resistant prostate cancer (CRPC) can occur in a patient with
      de novo metastatic disease who has received androgen-deprivation therapy. The
      initial evaluation of a patient who may have CRPC should include measurement of
      testosterone levels at the time of progression to confirm the presence of
      castrate levels of testosterone. Components of the workup include a baseline bone
      scan, a computed tomography scan, and a full blood panel. The follow-up of
      patients with metastatic CRPC should include measurement of prostate-specific
      antigen (PSA) levels as well as imaging studies. The most important clinical
      endpoint for these patients is survival, but others include symptoms, such as
      pain and fatigue; biochemical factors; and radiographic progression. Physicians
      must help manage symptoms, regardless of whether they arise from the treatment or
      the disease itself. For patients with metastatic CRPC, choice of treatment is
      driven primarily by whether the patient has asymptomatic or minimally
      symptomatic, versus symptomatic, disease. In this clinical roundtable monograph,
      experts discuss the diagnosis, prognosis, and management of patients with CRPC,
      with a focus on the best utilization of 4 recently approved agents: abiraterone
      acetate, sipuleucel-T, cabazitaxel, and denosumab.

PMID- 22361785
TI  - Structures during binding of cAMP receptor to promoter DNA: promoter search
      slowed by non-specific sites.
AB  - The kinetics of cAMP receptor (CAP) binding to promoter DNA has been studied by
      stopped-flow electric-dichroism at a reduced salt concentration, where the
      coupling of non-specific and specific binding can be observed directly.
      Amplitudes, rise and decay times of dichroism transients provide detailed
      information about the reaction and the structure of intermediates over more than
      six orders of magnitude on the time scale. CAP binding during the first
      milliseconds after mixing is indicated by an increase of both rise- and decay
      time constants. A particularly large increase of rise times reflects initial
      formation of non-symmetric complexes by protein binding to non-specific sites at
      DNA ends. The increase of the hydrodynamic dimensions continues up to ~1 s,
      before a decrease of time constants reflects transition to compact states with
      bent DNA up to the time range of ~10(3) s. The slow approach to CAP-induced DNA
      bending is due to non-specific complexes, which are formed initially and are
      converted slowly to the specific complex. At the salt concentration of 13.5 mM,
      conversion to specific complexes with bent DNA is completed after ~40 s at pH 8
      compared to >10(3) s at pH 7, resulting from a higher affinity of CAP to non
      specific sites at pH 7 than 8 by a factor of ~100. Thus, under the given
      conditions non-specific sites delay rather than facilitate formation of the
      specific complex with bent DNA. Experimental data obtained for a non-specific DNA
      clearly indicate the impact of pseudo-sites. The different electro-optical
      parameters have been combined in global fits.

PMID- 22361786
TI  - The relationship between entering medical students' backgrounds and career plans
      and their rural practice outcomes three decades later.
AB  - PURPOSE: Although many studies have investigated predictors of physician practice
      in rural areas, few have accounted for the importance of physicians' backgrounds.
      This study analyzed the relationship between the backgrounds and future career
      plans of entering medical students and their rural practice outcomes. METHOD: For
      1,111 graduates from Jefferson Medical College (JMC, classes of 1978-1982), three
      factors self-reported at matriculation and previously related to rural practice
      were obtained from the Jefferson Longitudinal Study of Medical Education: growing
      up rural, planning rural practice, and planning family medicine. Their 2007
      practice location was determined to be in a rural versus nonrural area. Analyses
      of graduates with various numbers of predictive factors (0-3) and rural practice
      were performed. RESULTS: Of the 762 JMC graduates (69%) with complete data, 172
      (23%) were practicing in rural areas. Of graduates with all three predictors, 45%
      (45/99) practiced in rural areas compared with 33% (48/145) of those with two
      predictors, 21% (42/198) with one predictor, and 12% (37/320) of those with none.
      Of physicians practicing in rural areas in 2007, only 22% had no predictors.
      CONCLUSIONS: Three factors known at the time of medical school matriculation have
      a powerful relationship with rural practice three decades later. Relatively few
      students without predictors practice in rural areas, which is particularly
      significant given subsequent factors known to be related to rural practice--for
      instance, rural curriculum, residency location, or spouse. These results have
      major implications for the role of the medical school admissions process in
      producing rural physicians.

PMID- 22361787
TI  - Sustaining an advisory dean program through continuous improvement and
      evaluation.
AB  - PURPOSE: In 2003, the advisory dean program at Columbia University College of
      Physicians and Surgeons was created to better connect students and faculty by
      supporting student academic progress and improving career advising. With the
      program in its eighth year, the authors were interested in identifying key
      factors in maintaining ongoing vitality and effectiveness. METHOD: In 2011, the
      authors conducted a reflective analysis to study the program, using available
      information from dean interviews, student surveys, meeting agendas, and program
      leader reflections, aided by the Bolman and Deal four-part framework for
      organizational functioning (structural, human resource, political, and symbolic).
      RESULTS: Structural factors included reframing program goals to match program
      activities, situating the program within broader academic advising and counseling
      resources, and increasing face time between entering students and their deans.
      Human resource factors included managing higher-than-expected turnover of deans
      with dean selection and orientation strategies that balance diversity and
      consistency, and providing ongoing training to promote continual professional
      growth. Political factors included balancing resources (e.g., money,
      administrative support) from the school and departments to help the deans protect
      and manage their time. Symbolic factors were related to leveraging the deans as
      symbols of institutional values and commitment to education (e.g., participation
      in the white coat ceremony), and being aware of "hidden meanings" associated with
      decisions within other frames (e.g., student-to-dean ratio). CONCLUSIONS: A
      variety of strategies across frames were used to maintain the program. This
      report can serve as a guide to program maintenance for other institutions.

PMID- 22361788
TI  - Using "standardized narratives" to explore new ways to represent faculty opinions
      of resident performance.
AB  - PURPOSE: Most efforts to develop reliable evaluations of clinical competence have
      been oriented toward deconstructing the requisite competencies into separate
      scales. However, many are questioning the value of this approach on theoretical
      and empirical bases. This study uses "standardized narratives" to explore a
      different approach to assessing resident performance. METHOD: In 2009, based on
      interviews with 19 experienced clinical faculty from two institutions, 16
      narrative profiles were created to represent the range of resident competence
      that clinical faculty might encounter during supervision. Fourteen clinicians
      from three institutions independently grouped the profiles into as many
      categories as necessary to reflect various levels of performance, described their
      categories, then ranked the individual profiles within each category. Then, in
      groups of three or four, participants negotiated a final ranking and grouping of
      the 16 profiles. RESULTS: Despite interesting idiosyncracies in the factors some
      participants identified as guiding their rankings, there was strong consistency
      across the 14 clinicians regarding the rankings (single-rater intraclass
      correlation [ICC] = 0.86) and groupings (single-rater ICC = 0.81) of the
      profiles. Similarly, across institutions, the four groups were highly consistent
      in their final negotiated rankings (single-group ICC = 0.91) and groupings
      (single-group ICC = 0.87) of the profiles. CONCLUSIONS: Faculty showed more
      consistency in their decisions of what constitutes excellent, competent, and
      problematic performance in residents than implied by current assessment
      techniques that require deconstruction of resident competencies. This use of
      standardized narratives points to interesting opportunities for more
      authentically codifying faculty opinions of residents.

PMID- 22361789
TI  - A national cohort study of U.S. medical school students who initially failed Step
      1 of the United States Medical Licensing Examination.
AB  - PURPOSE: To describe educational outcomes for a national cohort of U.S. medical
      students who initially failed Step 1 of the United States Medical Licensing
      Examination. METHOD: The authors analyzed deidentified, individualized records
      for the 1993-2000 cohort of U.S. medical school matriculants who both initially
      failed Step l and were no longer in medical school as of March 2, 2009, using
      multivariable logistic regression to identify factors associated with attempting,
      and initially passing, Step 2 Clinical Knowledge (CK). RESULTS: Of 6,594 students
      who failed Step l, 5,985 (90.8%) took Step 2CK. Women and Asian/Pacific Islander
      students were more likely to attempt Step 2CK; more recent matriculants and
      students with lower failing Step 1 scores were less likely. Of the 5,985 students
      who attempted Step 2CK, 4,168 (69.6%) initially passed. Women, students with
      higher Medical College Admission Test scores, and more recent matriculants were
      more likely to pass Step 2CK; Asian/Pacific Islander students, underrepresented
      minority students, older students, and students with lower failing Step 1 scores
      were less likely. Ninety percent of students in the study sample (5,952/6,594)
      ultimately graduated from medical school, including 99.5% (4,148/4,168) of those
      who initially passed, 96.7% (1,757/1,817) of those who initially failed, and 7.7%
      (47/609) of those who never attempted Step 2CK. CONCLUSIONS: The authors
      identified variables associated with educational outcomes among students who
      failed Step l. These findings can inform medical schools' efforts to develop
      tailored interventions to maximize the likelihood that students will take Step
      2CK and pass on the first attempt.

PMID- 22361790
TI  - Handoffs in the era of duty hours reform: a focused review and strategy to
      address changes in the Accreditation Council for Graduate Medical Education
      Common Program Requirements.
AB  - With changes in the Accreditation Council for Graduate Medical Education (ACGME)
      Common Program Requirements related to transitions in care effective July 1,
      2011, sponsoring institutions and training programs must develop a common
      structure for transitions in care as well as comprehensive curricula to teach and
      evaluate patient handoffs. In response to these changes, within the Duke
      University Health System, the resident-led Graduate Medical Education Patient
      Safety and Quality Council performed a focused review of the handoffs literature
      and developed a plan for comprehensive handoff education and evaluation for
      residents and fellows at Duke. The authors present the results of their focused
      review, concentrating on the three areas of new ACGME expectations--structure,
      education, and evaluation--and describe how their findings informed the broader
      initiative to comprehensively address transitions in care managed by residents
      and fellows. The process of developing both institution-level and program-level
      initiatives is reviewed, including the development of an interdisciplinary
      minimal data set for handoff core content, training and education programs, and
      an evaluation strategy. The authors believe the final plan fully addresses both
      Duke's internal goals and the revised ACGME Common Program Requirements and may
      serve as a model for other institutions to comprehensively address transitions in
      care and to incorporate resident and fellow leadership into a broad, health
      system-level quality improvement initiative.

PMID- 22361792
TI  - Associations of medical student personality and health/wellness characteristics
      with their medical school performance across the curriculum.
AB  - PURPOSE: To assess the relationships of cognitive and noncognitive performance
      predictors to medical student preclinical and clinical performance indicators
      across medical school years 1 to 3 and to evaluate the association of
      psychological health/wellness factors with performance. METHOD: In 2010, the
      authors conducted a cross-sectional, correlational, retrospective study of all
      175 students at the Saint Louis University School of Medicine who had just
      completed their third (first clinical) year. Students were asked to complete
      assessments of personality, stress, anxiety, depression, social support, and
      community cohesion. Performance measures included total Medical College Admission
      Test (MCAT) score, preclinical academic grades, National Board of Medical
      Examiners subject exam scores, United States Medical Licensing Examination Step 1
      score, clinical evaluations, and Humanism in Medicine Honor Society nominations.
      RESULTS: A total of 152 students (87%) participated. MCAT scores predicted
      cognitive performance indicators (academic tests), whereas personality variables
      (conscientiousness, extraversion, empathy) predicted noncognitive indicators
      (clinical evaluations, humanism nominations). Conscientiousness predicted all
      clinical skills, extraversion predicted clinical skills reflecting interpersonal
      behavior, and empathy predicted motivation. Health/wellness variables had limited
      associations with performance. In multivariate analyses that included control for
      shelf exam scores, conscientiousness predicted clinical evaluations, and
      extraversion and empathy predicted humanism nominations. CONCLUSIONS: This study
      identified two sets of skills (cognitive, noncognitive) used during medical
      school, with minimal overlap across the types of performance (e.g., exam
      performance versus clinical interpersonal skills) they predict. Medical school
      admission and evaluation efforts may need to be modified to reflect the
      importance of personality and other noncognitive factors.

PMID- 22361791
TI  - The patient handoff:  a comprehensive curricular blueprint for resident education
      to improve continuity of care.
AB  - In 2010, the Accreditation Council for Graduate Medical Education released its
      resident duty hours restrictions, requiring that faculty monitor their residents'
      patient handoffs to ensure that residents are competent in handoff
      communications. Although studies have reported the need to improve the
      effectiveness of the handoff and a variety of curricula have been suggested and
      implemented, a common method for teaching and evaluating handoff skills has not
      been developed. Also in 2010, engineers, informaticians, and physicians
      interested in patient handoffs attended a symposium in Savannah, Georgia, hosted
      by the Association for Computing Machinery, entitled Handovers and Handoffs:
      Collaborating in Turns. As a result of this symposium, a workgroup formed to
      develop practical and readily implementable educational materials for medical
      educators involved in teaching patient handoffs to residents. In this article,
      the result of that yearlong collaboration, the authors aim to provide clarity on
      the definition of the patient handoff, to review the barriers to performing
      effective handoffs in academic health centers, to identify available solutions to
      improve handoffs, and to provide a structured approach to educating residents on
      handoffs via a curricular blueprint. The authors' blueprint was developed to
      guide educators in customizing handoff education programs to fit their specific,
      local needs. Hopefully, it also will provide a starting point for future research
      into improving the patient handoff. Increasingly complex patient care
      environments require both innovations in handoff education and improvements in
      patient care systems to improve continuity of care.

PMID- 22361793
TI  - Which U.S. medical schools are providing the most physicians for the Appalachian
      region of the United States?
AB  - PURPOSE: To identify the U.S. medical schools with the most graduates practicing
      in rural, urban, and economically distressed areas of Appalachia. METHOD: Using
      June 2009 American Medical Association Physician Masterfile data, the authors
      identified physicians who graduated from medical school during 1991-2005 and were
      practicing in the 420 counties of the United States' Appalachian region. They
      then determined the U.S. medical schools with the most 2001-2005 graduates
      practicing in primary care (PC) or non-PC specialties in urban or rural areas and
      the most 1991-2005 graduates practicing in economically distressed/at-risk
      counties. RESULTS: Ten U.S. medical schools, led by the West Virginia School of
      Osteopathic Medicine, produced 50.5% (197/390) of 2001-2005 graduates practicing
      PC in rural areas of Appalachia; 10 schools, led by the University of Alabama
      School of Medicine, produced 44.1% (366/829) of graduates practicing PC in urban
      areas. During 2001-2005, 10 schools, led by the West Virginia University School
      of Medicine, graduated 42.1% (128/304) of non-PC physicians practicing in rural
      counties; 11 schools, led by the University of Alabama School of Medicine,
      graduated 38.5% (323/840) of non-PC physicians practicing in urban areas. All
      schools on the top 10 lists are located within states with Appalachian counties.
      University of Kentucky College of Medicine had the most 1991-2005 graduates
      practicing in economically distressed or at-risk counties. CONCLUSIONS:
      Physicians practicing in Appalachia are largely graduates of medical schools in
      or near the region. New schools being developed in the region may help reduce its
      continuing physician shortages.

PMID- 22361794
TI  - Does stereotype threat affect women in academic medicine?
AB  - Multiple complex factors contribute to the slow pace of women's advancement into
      leadership positions in academic medicine. In this article, the authors propose
      that stereotype threat--under which individuals who are members of a group
      characterized by negative stereotypes in a particular domain perform below their
      actual abilities in that domain when group membership is emphasized--may play an
      important role in the underrepresentation of women in leadership positions in
      academic medicine. Research to objectively assess the impact of stereotype threat
      for women in academic medicine is feasible and necessary to confirm this
      hypothesis. Still, a number of conditions present in the academic medicine
      community today have been shown to trigger stereotype threat in other settings,
      and stereotype threat fits with existing research on gender in academic medicine.
      In the meantime, academic health centers should implement relatively simple
      measures supported by experimental evidence from other settings to reduce the
      risk of stereotype threat, including (1) introducing the concept of stereotype
      threat to the academic medicine community, (2) engaging all stakeholders, male
      and female, to promote identity safety by enacting and making faculty aware of
      policies to monitor potential instances of discrimination, and training faculty
      to provide performance feedback that is free of gender bias, (3) counteracting
      the effects of sex segregation at academic health centers by increasing exposure
      to successful female leaders, (4) reducing gender stereotype priming by avoiding
      stereotypically male criteria for promotion, grants, and awards, and (5) building
      leadership efficacy among female physicians and scientists.

PMID- 22361795
TI  - Should efforts in favor of medical student diversity be focused during admissions
      or farther upstream?
AB  - PURPOSE: Traditional medical school admissions assessment tools may be limiting
      diversity. This study investigates whether the Multiple Mini-Interview (MMI) is
      diversity-neutral and, if so, whether applying it with greater weight would
      dilute the anticipated negative impact of diversity-limiting admissions measures.
      METHOD: Interviewed applicants to six medical schools in 2008 and 2009 underwent
      MMI. Predictor variables of MMI scores, grade point average (GPA), and Medical
      College Admission Test (MCAT) scores were correlated with diversity measures of
      age, gender, size of community of origin, income level, and self-declared
      aboriginal status. A subset of the data was then combined with variable weight
      assigned to predictor variables to determine whether weighting during the
      applicant selection process would affect diversity among chosen applicants.
      RESULTS: MMI scores were unrelated to gender, size of community of origin, and
      income level. They correlated positively with age and negatively with aboriginal
      status. GPA and MCAT correlated negatively with age and aboriginal status, GPA
      correlated positively with income level, and MCAT correlated positively with size
      of community of origin. Even extreme combinations of MMI and GPA weightings
      failed to increase diversity among applicants who would be selected on the basis
      of weighted criteria. CONCLUSIONS: MMI could not neutralize the diversity
      limiting properties of academic scores as selection criteria to interview. Using
      academic scores in this way causes range restriction, counteracting attempts to
      enhance diversity using downstream admissions selection measures such as MMI.
      Diversity efforts should instead be focused upstream. These results lend further
      support for the development of pipeline programs.

PMID- 22361796
TI  - Which factors predict the likelihood of reapplying to medical school? An analysis
      by gender.
AB  - PURPOSE: To explore factors associated with becoming a repeat applicant to
      medical school--specifically, factors involving alternative educational and
      career plans and educational indebtedness--and how they differ by gender. METHOD:
      Using deidentified 2009 and 2010 American Medical College Application Service
      (AMCAS) data, the authors determined the potential and actual 2010 repeat
      applicants among first-time applicants who were not accepted to medical school in
      2009. Using logistic regression models, they then analyzed the deidentified 2008
      Pre-MCAT Questionnaire (PMQ) responses of those potential 2010 repeat applicants
      who had participated in the PMQ to examine associations between aspirants' self
      reported alternative educational and career (Plan B) options as well as levels of
      indebtedness and the likelihood of reapplying. Using population-level demographic
      data from AMCAS, the authors weighted analyses to more accurately reflect the
      actual population of potential repeat applicants. They also explored gender
      related differences. RESULTS: Considering as a Plan B applying to a different
      graduate degree program--business, law, science, another health profession-
      decreased the likelihood that an unsuccessful 2009 first-time applicant would
      reapply to medical school in 2010. Aspirants who had more than $20,000 of
      educational debt were also less likely to become repeat applicants. In separate
      analyses for men and women, factors associated with the likelihood of reapplying
      differed noticeably. CONCLUSIONS: The authors' findings provide insight into how
      medical school aspirants make decisions about their career and educational
      pathways, and how factors associated with those decisions shape the social
      composition of the medical school applicant pool.

PMID- 22361797
TI  - Differential student attrition and differential exposure mask effects of problem
      based learning in curriculum comparison studies.
AB  - PURPOSE: Studies that compare the effects of problem-based and conventional
      medical curricula on student performance generally show no significant
      differences. However, curriculum comparison studies are at best quasi
      experimental, so they are prone to forms of selection bias. The purpose of this
      study was to reanalyze data from such comparisons by controlling for two
      potential biases: differential student attrition and differential exposure.
      METHOD: The authors reanalyzed 104 previously published comparisons involving a
      single, problem-based medical school in the Netherlands (Maastricht University's
      medical school), using student attrition and study duration data from this school
      and the schools with which it was compared. The authors removed bias by
      reequalizing the comparison groups in terms of attrition and study duration.
      RESULTS: The uncorrected data showed no differences between problem-based and
      conventional curricula: Mean effect sizes as expressed by Cohen d were 0.02 for
      medical knowledge and 0.07 for diagnostic reasoning. However, the reanalysis
      demonstrated medium-level effect sizes favoring the problem-based curriculum.
      After corrections for attrition and study duration, the mean effect size for
      knowledge acquisition was 0.31 and for diagnostic reasoning was 0.51.
      CONCLUSIONS: Effects of the Maastricht problem-based curriculum were masked by
      differential attrition and differential exposure in the original studies. Because
      this school has been involved in many studies included in influential literature
      reviews published in the past 20 years, the authors' findings have implications
      for the assessment of the value of problem-based learning put forward by these
      reviews.

PMID- 22361798
TI  - What do residents do when not working or sleeping? A multispecialty survey of 36
      residency programs.
AB  - PURPOSE: To determine how residents spend their time when not working or
      sleeping, and to examine correlates of these outside activities. METHOD: In 2009,
      the authors surveyed 36 internal medicine, surgery, pediatrics, and obstetrics
      gynecology programs. Residents answered questions about their recently completed
      first and second residency years, including, "During your past year of residency,
      outside of working hours, about how often did you...," followed by 10 listed
      activities and a four-point rating scale (1 = "less than once a week"; 4 =
      "almost daily"). RESULTS: The most frequent activity reported across all 634
      respondents was using the Internet, followed by watching television and doing
      household tasks. The lowest reported activity was moonlighting, followed by
      seeing a movie. K-cluster analyses divided residents into three clusters: (1)
      "Friend Focused," reporting higher means for time with friends, Internet use,
      physical exercise, and watching television, (2) "Family Focused," reporting
      higher means for time with family, Internet use, household tasks, and watching
      television, and (3) "Low Activity," reporting the lowest ratings for all
      activities. Comparisons among these three clusters showed the Low Activity
      residents to have significantly higher scores on validated depression, anxiety,
      and sleepiness scales; higher stress; more reported work hours and sleep
      deprivation; and lower ratings for satisfaction, time with attendings, and
      learning. Scores for Friend-Focused and Family-Focused clusters were similar to
      each other. CONCLUSIONS: These data provide new information about the residency
      experience and suggest that activities outside of work and sleep hours correlate
      highly with residents' mood, learning, and satisfaction.

PMID- 22361799
TI  - Students versus faculty members as admissions interviewers:  comparisons of
      ratings data and admissions decisions.
AB  - PURPOSE: To explore variations both in interview ratings data and in medical
      school admissions decisions when current medical students do and do not
      participate in interviewing applicants. METHOD: The research team conducted this
      randomized controlled trial by performing identical analyses for each of six
      independent cohorts of applicants (n = 3,868) to Baylor College of Medicine for
      the academic years 2005-2006 through 2010-2011. A pair of randomly selected
      interviewers--either two faculty members or a faculty member and a student-
      interviewed each applicant in a one-on-one interview. RESULTS: Interviewer pairs
      randomly structured to include either two faculty members (n = 1,523) or one
      faculty member and one student (n = 2,345) produced ratings of similar means as
      well as homogeneity across ratings. The structure of the rater pairs, as
      expected, was not predictive of the final admissions decisions after the authors
      took into account Medical College Admission Test scores and grade point average.
      CONCLUSIONS: These results, showing that student involvement does not compromise
      the ratings of interviewed applicants, support the continued involvement of
      students in medical school admissions interviews.

PMID- 22361800
TI  - Addressing the leadership gap in medicine:  residents' need for systematic
      leadership development training.
AB  - All clinicians take on leadership responsibilities when delivering care. Evidence
      suggests that effective clinical leadership yields superior clinical outcomes.
      However, few residency programs systematically teach all residents how to lead,
      and many clinicians are inadequately prepared to meet their day-to-day clinical
      leadership responsibilities. The purpose of this article is twofold: first, to
      make the case for the need to refocus residency education around the development
      of outstanding "frontline" clinical leaders and, second, to provide an evidence
      based framework for designing formal leadership development programs for
      residents. The authors first present a definition of clinical leadership and
      highlight evidence that effective frontline clinical leadership improves both
      clinical outcomes and satisfaction for patients and providers. The authors then
      discuss the health care "leadership gap" and describe barriers to implementing
      leadership development training in health care. Next, they present evidence that
      leaders are not just "born" but, rather, can be "made," and offer a set of best
      practices to facilitate the design of leadership development programs. Finally,
      the authors suggest approaches to mitigating barriers to implementing leadership
      development programs and highlight the major reasons why health care delivery
      organizations, residency programs, and national accreditation bodies must make
      comprehensive leadership education an explicit goal of residency training.

PMID- 22361801
TI  - A systematic review:  the effect of clinical supervision on patient and residency
      education outcomes.
AB  - PURPOSE: To summarize the literature regarding the effect of clinical supervision
      on patient and educational outcomes, especially in light of the recent (2010)
      Accreditation Council for Graduate Medical Education report that recommends
      augmented supervision to improve resident education and patient safety. METHOD:
      The authors searched the English-language literature from 1966 to 2010 using
      electronic databases and a hand search. They included studies that described a
      controlled design, and they have relayed the effects of supervision on patient-
      and education-related outcomes. Two authors abstracted prescribed data from the
      reviewed studies. The authors rated the quality of each study using the Medical
      Education Research Study Quality Instrument. RESULTS: Twenty-four articles across
      a variety of specialties (i.e., psychiatry, emergency medicine, surgery,
      anesthesia, and internal medicine) met inclusion criteria. Studies demonstrated
      that enhanced supervision in already-supervised activities resulted in improved
      patient- or education-related outcomes. Studies were limited by small sample
      sizes, nonrandomized designs, and a lack of objective measures of clinical
      supervision. CONCLUSIONS: Enhanced clinical supervision of trainees has been
      associated with improved patient- and education-related outcomes in published
      studies. Future work should focus on developing validated measures of the effects
      of clinical supervision.

PMID- 22361802
TI  - Medical school rural programs:  a comparison with international medical graduates
      in addressing state-level rural family physician and primary care supply.
AB  - PURPOSE: Comprehensive medical school rural programs (RPs) have made demonstrable
      contributions to the rural physician workforce, but their relative impact is
      uncertain. This study compares rural primary care practice outcomes for RP
      graduates within relevant states with those of international medical graduates
      (IMGs), also seen as ameliorating rural physician shortages. METHOD: Using data
      from the 2010 American Medical Association Physician Masterfile, the authors
      identified all 1,757 graduates from three RPs (Jefferson Medical College's
      Physician Shortage Area Program; University of Minnesota Medical School Duluth;
      University of Illinois College of Medicine at Rockford's Rural Medical Education
      Program) practicing in their respective states, and all 6,474 IMGs practicing in
      the same states and graduating the same years. The relative likelihoods of RP
      graduates versus IMGs practicing rural family medicine and rural primary care
      were compared. RESULTS: RP graduates were 10 times more likely to practice rural
      family medicine than IMGs (relative risk [RR] = 10.0, confidence interval [CI]
      8.7-11.6, P < .001) and almost 4 times as likely to practice any rural primary
      care specialty (RR 3.8, CI 3.5-4.2, P < .001). Overall, RPs produced more rural
      family physicians than the IMG cohort (376 versus 254). CONCLUSIONS: Despite
      their relatively small size, RPs had a significant impact on rural family
      physician and primary care supply compared with the much larger cohort of IMGs.
      Wider adoption of the RP model would substantially increase access to care in
      rural areas compared with increasing reliance on IMGs or unfocused expansion of
      traditional medical schools.

PMID- 22361803
TI  - An innovative clerkship module focused on patients with disabilities.
AB  - Lack of medical training results in physicians being unprepared to provide care
      to people with disabilities, which, in turn, contributes to the substantial
      health disparities that are evident in this population. Few medical schools or
      primary care residencies address the care of adults with disabilities.
      Competencies and guidelines to assist American physicians in caring for patients
      with physical or intellectual disabilities have yet to be established, thus
      making educational goals unclear. This article describes one novel training
      module regarding people with disabilities that was developed at the University of
      South Florida Health, Morsani College of Medicine (USF) and inserted into the
      primary care clerkship during a major curriculum redesign in 2005. Since then,
      all USF third-year medical students have been required to participate in this
      disability-related course component. The authors describe the module's
      development and integration into the primary care clerkship, as well as the
      specific elements of their curriculum. By using a variety of teaching modalities
      in the classroom and community, and especially by involving people with
      disabilities themselves, the medical students have a very comprehensive learning
      experience regarding people who have physical, sensory, or intellectual
      disabilities. The authors have been able to show that USF medical students, on
      completion of this module, demonstrate improved knowledge, attitudes, and comfort
      in caring for people with disabilities, which the authors believe will lead to
      improved health and health care access for this underserved population.
      Suggestions for program replication, including common challenges, are also
      discussed.

PMID- 22361804
TI  - Transgenic rice grains expressing a heterologous rho-hydroxyphenylpyruvate
      dioxygenase shift tocopherol synthesis from the gamma to the alpha isoform
      without increasing absolute tocopherol levels.
AB  - We generated transgenic rice plants overexpressing Arabidopsis thaliana rho
      hydroxyphenylpyruvate dioxygenase (HPPD), which catalyzes the first committed
      step in vitamin E biosynthesis. Transgenic grains accumulated marginally higher
      levels of total tocochromanols than controls, reflecting a small increase in
      absolute tocotrienol synthesis (but no change in the relative abundance of the
      alpha and gamma isoforms). In contrast, there was no change in the absolute
      tocopherol level, but a significant shift from the gamma to the alpha isoform.
      These data confirm HPPD is not rate limiting, and that increasing flux through
      the early pathway reveals downstream bottlenecks that act as metabolic tipping
      points.

PMID- 22361805
TI  - Definition of temperature thresholds: the example of the French heat wave warning
      system.
AB  - Heat-related deaths should be somewhat preventable. In France, some prevention
      measures are activated when minimum and maximum temperatures averaged over three
      days reach city-specific thresholds. The current thresholds were computed based
      on a descriptive analysis of past heat waves and on local expert judgement. We
      tested whether a different method would confirm these thresholds. The study was
      set in the six cities of Paris, Lyon, Marseille, Nantes, Strasbourg and Limoges
      between 1973 and 2003. For each city, we estimated the excess in mortality
      associated with different temperature thresholds, using a generalised additive
      model, controlling for long-time trends, seasons and days of the week. These
      models were used to compute the mortality predicted by different percentiles of
      temperatures. The thresholds were chosen as the percentiles associated with a
      significant excess mortality. In all cities, there was a good correlation between
      current thresholds and the thresholds derived from the models, with 0 degrees C
      to 3 degrees C differences for averaged maximum temperatures. Both set of
      thresholds were able to anticipate the main periods of excess mortality during
      the summers of 1973 to 2003. A simple method relying on descriptive analysis and
      expert judgement is sufficient to define protective temperature thresholds and to
      prevent heat wave mortality. As temperatures are increasing along with the
      climate change and adaptation is ongoing, more research is required to understand
      if and when thresholds should be modified.

PMID- 22361806
TI  - Comment on: Prospective changes in body image dissatisfaction among adolescent
      bariatric patients: the importance of body size estimation.

PMID- 22361807
TI  - Robotic-assisted Roux-en-Y gastric bypass: update from 2 high-volume centers.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) is a challenging
      operation in the most experienced hands. Robotic surgery allows the capabilities
      of the minimally invasive surgeon to be extended. An increasing number of robotic
      gastric bypasses are being performed each year with the assumption that the
      complication rates are decreased. The objectives of the present study were to
      review the results of robotic-assisted RYGB (RARYGB) from 2 high-volume centers,
      including 1 university and 1 private practice. METHODS: We report the most
      recently compiled, largest series of RARYGB in the world to show the
      effectiveness, morbidity, and mortality of this method. Databases were searched
      for patients undergoing RARYGB from 2002 to 2010, and the endpoints were
      recorded. RESULTS: A total of 1100 RARYGBs matched our search. The patients had a
      mean preoperative age of 46.9 years, mean weight of 131.9 kg, and mean body mass
      index of 47.9 kg/m(2). The mean operative time was 155 minutes. There were no
      conversions. The mean body mass index was 39.8 kg/m(2) at 3 months
      postoperatively (79% follow-up). Complications were few, and included 2 cases of
      pulmonary embolism (.19%), 3 cases of deep venous thrombosis (.27%), 1 case of
      gastrojejunal anastomotic leak (.09%), and 9 cases of staple line bleeding
      (.82%). No patients died. CONCLUSION: RARYGB is safe and effective. Although the
      operative time might be increased, the complication rates, most notably of
      anastomotic leak, are extremely low.

PMID- 22361808
TI  - Synthesis and protein binding studies of a peptide fragment of clathrin assembly
      protein AP180 bearing an O-linked beta-N-acetylglucosaminyl-6-phosphate
      modification.
AB  - A novel post-translational modification of threonine, beta-N-acetylglucosaminyl
      phosphate, was recently discovered on assembly protein AP180, a protein which
      plays a crucial role in clathrin coated vesicle formation in synaptic vesicle
      endocytosis (SVE). Herein, we report studies aimed at probing the effect of this
      modification on binding to proteins in rat brain lysate using pull down
      experiments with peptide fragments of AP180.

PMID- 22361809
TI  - Connexin 26 in psoriatic skin before and after two conventional therapeutic
      modalities: methotrexate and PUVA.
AB  - BACKGROUND: Direct intercellular signaling, which controls keratinocyte behavior,
      proliferation and differentiation, occurs through gap junctions. Altered
      expression of connexins may play a role in the development of psoriatic lesions.
      OBJECTIVES: We estimated connexin 26 (Cx26) mRNA in psoriatic patients and
      investigated whether the standard therapeutic modalities (methotrexate and PUVA)
      exert their anti-psoriatic activity partially through altering Cx26 mRNA levels.
      We also detected Cx26 in skin biopsies by immunohistochemistry. RT-PCR measured
      Cx26 mRNA levels in 24 chronic plaque psoriasis patients. Group A received
      intramuscular methotrexate and group B was treated by PUVA for ten weeks, each
      followed by measurement of Cx26 mRNA levels and immunohistochemistry. Twelve
      healthy volunteers served as controls. RESULTS: Cx26 mRNA expression was
      significantly higher in the patients before treatment than in controls (P<0.001).
      Post treatment levels were significantly lower than pre-treatment levels
      (P<0.001), however, significantly higher than in controls (P<0.001). Methotrexate
      and PUVA caused significant reductions in Cx26 mRNA expression (P=0.002, P=0.028
      respectively). Post treatment levels were slightly significantly lower in the
      methotrexate group than in the PUVA group (P=0.046). The reduction in Cx26 mRNA
      expression was significantly positively correlated with the clinical improvement
      of the psoriatic plaque (P=0.002). Immunostaining of Cx26 decreased after
      treatment. CONCLUSION: Altered expression of the gap junction protein Cx26 may
      have a role in the development of the psoriatic phenotype. Both methotrexate and
      PUVA significantly lowered the expression of Cx26 mRNA and protein.

PMID- 22361810
TI  - Enhanced photocurrent production from thin films of Ru(II) metallopolymer/Dawson
      polyoxotungstate adducts under visible irradiation.
AB  - Thin films of polyoxometalates that are sensitized with a Ru(II) metallopolymer
      generate significant photocurrents in the presence of benzyl alcohol and visible
      light. Significantly, the photocurrent generated by the tungstate based adduct,
      alpha-[P(2)W(18)O(62)](6-), is approximately seven fold larger than that found
      for the Dawson polyoxomolybdate alpha-[S(2)Mo(18)O(62)](4-).

PMID- 22361811
TI  - Light-activated nanotube-porphyrin conjugates as effective antiviral agents.
AB  - Porphyrins have been used for photodynamic therapy (PDT) against a wide range of
      targets like bacteria, viruses and tumor cells. In this work, we report porphyrin
      conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents.
      Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid
      functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon
      nanotubes as scaffolds because of their ease of recovery from a solution through
      filtration. In the presence of visible light, NT-P was found to significantly
      reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be
      used effectively against influenza viruses with little or no chance of them
      developing resistance to the treatment. Furthermore, NT-P can be easily recovered
      through filtration which offers a facile strategy to reuse the active porphyrin
      moiety to its fullest extent. Thus NT-P conjugates represent a new approach for
      preparing ex vivo reusable antiviral agents.

PMID- 22361813
TI  - Nigrostriatal overabundance of alpha-synuclein leads to decreased vesicle density
      and deficits in dopamine release that correlate with reduced motor activity.
AB  - alpha-Synuclein (alpha-syn) is a presynaptic protein present at most nerve
      terminals, but its function remains largely unknown. The familial forms of
      Parkinson's disease associated with multiplications of the alpha-syn gene locus
      indicate that overabundance of this protein might have a detrimental effect on
      dopaminergic transmission. To investigate this hypothesis, we use adeno
      associated viral (AAV) vectors to overexpress human alpha-syn in the rat
      substantia nigra. Moderate overexpression of either wild-type (WT) or A30P alpha
      syn differs in the motor phenotypes induced, with only the WT form generating
      hemiparkinsonian impairments. Wild-type alpha-syn causes a reduction of dopamine
      release in the striatum that exceeds the loss of dopaminergic neurons, axonal
      fibers, and the reduction in total dopamine. At the ultrastructural level, the
      reduced dopamine release corresponds to a decreased density of dopaminergic
      vesicles and synaptic contacts in striatal terminals. Interestingly, the membrane
      binding-deficient A30P mutant does neither notably reduce dopamine release nor it
      cause ultrastructural changes in dopaminergic axons, showing that alpha-syn's
      membrane-binding properties are critically involved in the presynaptic defects.
      To further determine if the affinity of the protein for membranes determines the
      extent of motor defects, we compare three forms of alpha-syn in conditions
      leading to pronounced degeneration. While membrane-binding alpha-syns (wild-type
      and A53T) induce severe motor impairments, an N-terminal deleted form with
      attenuated affinity for membranes is inefficient in inducing motor defects.
      Overall, these results demonstrate that alpha-syn overabundance is detrimental to
      dopamine neurotransmission at early stages of the degeneration of nigrostriatal
      dopaminergic axons.

PMID- 22361816
TI  - Targeting dendritic cells with antigen via dendritic cell-associated promoters.
AB  - The induction of tumor-specific immune responses is largely dependent on the
      ability of dendritic cells (DCs) to present tumor-associated antigens to T
      lymphocytes. Therefore, we investigated the use of DC-associated promoter-driven
      genetic vaccines to specifically target DC in vivo. Restricted expression of
      vaccine-encoding genes in DC should enhance specificity and improves their safety
      for clinical applications. Hereto, 3-5 kb upstream sequences of the murine genes
      encoding CD11c, DC-SIGN, DC-STAMP and Langerin were isolated, characterized and
      subcloned into enhanced green fluorescent protein (EGFP) reporter constructs.
      Upon electroporation, EGFP was expressed in DC cell lines, but not in other cell
      lines, confirming DC-restricted promoter activity. When these promoters were
      cloned into a construct upstream of the gene for ovalbumin (OVA), it appeared
      that DC-STAMP promoter-driven expression of OVA (pDCSTAMP/OVA) in DC yielded the
      most efficient OVA-specific CD4+ and CD8+ T-cell responses in vitro.
      Administration of pDC-STAMP/OVA in vivo, using the tattoo gun vaccination system,
      evoked specific immune responses as evidenced in a mouse tumor model. Adoptively
      transferred pDC-STAMP/OVA-transfected DCs induced strong CD8+ T-cell
      proliferation in vivo. These experiments demonstrate that our DC-directed
      promoter constructs are potential tools to restrict antigen expression in DC and
      could be implemented to modulate DC function by the introduction of relevant
      proteins.

PMID- 22361817
TI  - "I stand alone." An ethnodrama about the (dis)connections between a client and
      professionals in a residential care home.
AB  - Client participation in elderly care organizations requires shifting traditional
      power relations and establishing communicative action that involves the
      lifeworlds of clients and professionals alike. This article describes a
      particular form of client participation in which one client was part of a team of
      professionals in a residential care home. Their joint remit was to plan the
      implementation of a new personal care file for residents. We describe the
      interactions within this team through an ethnodrama, based on participant
      observations and the embodied presence of the researcher (first author). The
      narratives and voices of all team members are dramatized in this ethnodrama.
      Throughout the project the team members experienced confusion relating to the
      confrontation between lifeworld and system, as experienced by the client and
      professionals in the team. We analyze these tensions by making use of a
      Habermasian theoretical framework. We conclude that forms for collective client
      participation in residential care homes should be developed based on
      communicative action between clients and professionals, with room for emotional
      engagement. 

PMID- 22361818
TI  - Expression and localization of two SecA homologs in the unicellular red alga
      Cyanidioschyzon merolae.
AB  - SecA is an ATP-driven motor for Sec translocase that participates in bacterial
      protein export and thylakoidal import in plants. We have reported that
      Cyanidioschyzon merolae, a unicellular red alga, possesses a nuclear-encoded
      secA(nuc) and a plastid-encoded secA(pt) gene. In this study we found that the
      amount of SecA(nuc) protein almost quadrupled at high temperature, whereas that
      of the SecA(pt) protein increased far less. We were also able to determine the
      localization of both SecAs to the chloroplast by immunofluorescence and
      immunoelectron microscopy. We suggest that SecA(nuc) has an important role in the
      chloroplast at high temperatures.

PMID- 22361819
TI  - End-stage pulmonary disease and brachial plexus regional anesthesia: their
      implications on perioperative pulmonary function.
AB  - The authors present the challenging clinical scenario of managing a patient with
      end-stage chronic obstructive pulmonary disease requiring anesthesia for a
      proximal humerus open reduction and internal fixation who likely would have
      failed to wean from mechanical ventilation if general anesthesia and endotracheal
      intubation had been chosen as the maintenance technique. They discuss the effects
      of general and regional anesthesia on respiratory physiology and describe the
      perioperative implications of severe pulmonary disease. They also review the
      various brachial plexus block options that could achieve a satisfactory outcome,
      with the objective of helping guide practitioners to a rational choice of
      anesthetic techniques when caring for patients with end-stage pulmonary disease.

PMID- 22361820
TI  - Anesthetic considerations during minimally invasive mitral valve surgery.
AB  - Advances in instruments and visualization tools as well as circulatory systems
      for cardiopulmonary bypass during the late 1990s have stimulated widespread
      adoption of minimally invasive mitral valve surgery (MIMVS). Today, MIMVS is the
      standard approach for many surgeons and institutions. There are multiple benefits
      of MIMVS. Patient satisfaction and improved cosmesis are important. Additionally,
      studies have consistently shown faster recovery times and less associated pain
      with MIMVS. Statistically significant improvement in bleeding, transfusion,
      incidence of atrial fibrillation, and time to resumption of normal activities
      with MIMVS has also been shown when comparing MIMVS with conventional mitral
      surgery. Most important, these benefits have been achieved without sacrificing
      perioperative safety or durability of surgical repair. Although a steep learning
      curve still exists given the high level of case complexity, continued development
      fueled by increasing patient demand may allow for even further expansion in the
      use of minimal invasive techniques.

PMID- 22361821
TI  - A bimodal influence of thyroid hormone on cerebellum oligodendrocyte
      differentiation.
AB  - Thyroid hormone (T(3)) can trigger a massive differentiation of cultured
      oligodendrocytes precursor cells (OPC) by binding the nuclear T(3) receptor
      alpha1 (TRalpha1). Whether this reflects a physiological function of TRalpha1
      remains uncertain. Using a recently generated mouse model, in which CRE/loxP
      recombination is used to block its function, we show that TRalpha1 acts at two
      levels for the in vivo differentiation of OPC in mouse cerebellum. At the early
      postnatal stage, it promotes the secretion of several neurotrophic factors by
      acting in Purkinje neurons and astrocytes, defining an environment suitable for
      OPC differentiation. At later stages, TRalpha1 acts in a cell-autonomous manner
      to ensure the complete arrest of OPC proliferation. These data explain
      contradictory observations made on various models and outline the importance of
      T(3) signaling both for synchronizing postnatal neurodevelopment and restraining
      OPC proliferation in adult brain.

PMID- 22361823
TI  - Melanocortin-induced PKA activation inhibits AMPK activity via ERK-1/2 and LKB-1
      in hypothalamic GT1-7 cells.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH)-induced activation of the
      melanocortin-4 receptor in hypothalamic neurons increases energy expenditure and
      inhibits food intake. Active hypothalamic AMP-activated protein kinase (AMPK) has
      recently been reported to enhance food intake, and in vivo experiments suggested
      that intrahypothalamic injection of melanocortins decreased food intake due to
      the inhibition of AMPK activity. However, it is not clear whether alpha-MSH
      affects AMPK via direct intracellular signaling cascades or if the release of
      paracrine factors is involved. Here, we used a murine, hypothalamic cell line
      (GT1-7 cells) and monitored AMPK phosphorylation at Thr(172), which has been
      suggested to increase AMPK activity. We found that alpha-MSH dephosphorylated
      AMPK at Thr(172) and consequently decreased phosphorylation of the established
      AMPK substrate acetyl-coenzyme A-carboxylase at Ser(79). Inhibitory effects of
      alpha-MSH on AMPK were blocked by specific inhibitors of protein kinase A (PKA)
      or ERK-1/2, pointing to an important role of both kinases in this process.
      Because alpha-MSH-induced activation of ERK-1/2 was blunted by PKA inhibitors, we
      propose that ERK-1/2 serves as a link between PKA and AMPK in GT1-7 cells.
      Furthermore, down-regulation of liver kinase B-1, but not inhibition of calcium
      calmodulin-dependent kinase kinase-beta or TGFbeta-activated kinase-1 decreased
      basal phosphorylation of AMPK and its dephosphorylation induced by alpha-MSH.
      Thus, we propose that alpha-MSH inhibits AMPK activity via a linear pathway,
      including PKA, ERK-1/2, and liver kinase B-1 in GT1-7 cells. Given the importance
      of the melanocortin system in the formation of adipositas, detailed knowledge
      about this pathway might help to develop drugs targeting obesity.

PMID- 22361822
TI  - Protein arginine methyltransferase 5 (Prmt5) promotes gene expression of
      peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and its target
      genes during adipogenesis.
AB  - Regulation of adipose tissue formation by adipogenic-regulatory proteins has long
      been a topic of interest given the ever-increasing health concerns of obesity and
      type 2 diabetes in the general population. Differentiation of precursor cells
      into adipocytes involves a complex network of cofactors that facilitate the
      functions of transcriptional regulators from the CCATT/enhancer binding protein,
      and the peroxisome proliferator-activated receptor (PPAR) families. Many of these
      cofactors are enzymes that modulate the structure of chromatin by altering
      histone-DNA contacts in an ATP-dependent manner or by posttranslationally
      modifying the histone proteins. Here we report that inhibition of protein
      arginine methyltransferase 5 (Prmt5) expression in multiple cell culture models
      for adipogenesis prevented the activation of adipogenic genes. In contrast,
      overexpression of Prmt5 enhanced adipogenic gene expression and differentiation.
      Chromatin immunoprecipitation experiments indicated that Prmt5 binds to and
      dimethylates histones at adipogenic promoters. Furthermore, the presence of Prmt5
      promoted the binding of ATP-dependent chromatin-remodeling enzymes and was
      required for the binding of PPARgamma2 at PPARgamma2-regulated promoters. The
      data indicate that Prmt5 acts as a coactivator for the activation of adipogenic
      gene expression and promotes adipogenic differentiation.

PMID- 22361824
TI  - Semiology of skin toxicity associated with epidermal growth factor receptor
      (EGFR) inhibitors.
AB  - PURPOSE: Advances in the understanding of the mechanisms involved in oncogenesis
      have led to the development of so-called targeted therapies such as epidermal
      growth factor receptor (EGFR) inhibitors, which take on an increasingly important
      role in the management of cancer. These treatments have the advantage not to
      trigger the adverse effects traditionally encountered with chemotherapy, such as
      nausea, vomiting or haematological toxicity. However, they do cause new forms of
      toxicity: the most common one is skin toxicity. It is important to be aware of it
      because it can be debilitating, adversely impacting patients' quality of life and
      altering treatment compliance, although it appears to be correlated with
      treatment response in certain series. Non-specialists can have difficulty in
      recognising this unusual skin toxicity. METHODS: The dermatologic side effects
      most frequently triggered by EGFR inhibitors are discussed in this article.
      RESULTS: They are divided into three categories depending on their target:
      inflammation of the pilo-sebaceous follicle, represented by EGFR inhibitor
      associated folliculitis, which occurs at an early stage and is frequent;
      alteration in the skin barrier, primarily responsible for xerosis, fissures and
      pruritus, which are frequent and delayed; and lesions of the skin appendages
      (paronychia, pyogenic granuloma, hair changes), which are delayed and less
      frequent. CONCLUSION: It is essential for all practitioners concerned to know
      about these dermatologic side effects in order to ensure better global management
      of patients, particularly in terms of quality of life.

PMID- 22361825
TI  - Surrender as a form of active acceptance among breast cancer survivors receiving
      Psycho-Spiritual Integrative Therapy.
AB  - PURPOSE: The purpose of this study was to describe a domain of spiritual coping
      known as "surrender," as experienced among women diagnosed with breast cancer who
      participated in Psycho-Spiritual Integrative Therapy (PSIT). Surrender is a
      concept similar to active acceptance, which has been studied extensively, but
      surrender in the context of spiritual supportive care has received little
      attention. METHODS: After participating in PSIT, which includes exercises in
      surrender, 23 participants completed an open-ended questionnaire about their
      experiences of surrender. Twelve women whose responses were most complete and
      expressive were selected to be analyzed for this study. A thematic analysis was
      conducted to better understand how surrender experiences may contribute to
      supportive care. RESULTS: Four distinct themes were identified: experience of
      surrender, facilitation of surrender, inhibition of surrender, and ease and
      completeness of surrender. Although the manifestations of surrender varied, women
      were consistent in describing these experiences positively. CONCLUSIONS: These
      findings build upon previous evidence that spirituality, optimism, and active
      acceptance have a positive impact on well-being in cancer patients. The findings
      provide insight into the usefulness of PSIT for women with breast cancer and
      inform future research on the intervention.

PMID- 22361826
TI  - Prospective observational Italian study on palliative sedation in two hospice
      settings: differences in casemixes and clinical care.
AB  - PURPOSE: Palliative sedation (PS) has been defined as the use of sedative
      medications to relieve intolerable suffering from refractory symptoms by a
      reduction in patient consciousness. It is sometimes necessary in end-of-life care
      when patients present refractory symptoms. We investigated PS for refractory
      symptoms in different hospice casemixes in order to (1) assess clinical decision
      making, (2) monitor the practice of PS, and (3) examine the impact of PS on
      survival. METHODS: This observational longitudinal cohort study was conducted
      over a period of 9 months on 327 patients consecutively admitted to two 11-bed
      Italian hospices (A and B) with different casemixes in terms of median patient
      age (hospice A, 66 years vs. hospice B, 73 years; P = 0.005), mean duration of
      hospice stay (hospice A, 13.5 days vs. hospice B, 18.3 days; P = 0.005), and
      death rate (hospice A, 57.2% vs. hospice B, 89.9%; P < 0.0001). PS was monitored
      using the Richmond Agitation-Sedation Scale (RASS). Sedated patients constituted
      22% of the total admissions and 31.9% of deceased patients, which did not prove
      to be significantly different in the two hospices after adjustment for casemix.
      RESULTS: Patient involvement in clinical decision-making about sedation was
      significantly higher in hospice B (59.3% vs. 24.4%; P = 0.007). Family
      involvement was 100% in both hospices. The maximum level of sedation (RASS, -5)
      was necessary in only 58.3% of sedated patients. Average duration of sedation was
      similar in the two hospices (32.2 h [range, 2.5-253.0]). Overall survival in
      sedated and nonsedated patients was superimposable, with a trend in favor of
      sedated patients. CONCLUSIONS: PS represents a highly reproducible clinical
      intervention with its own indications, assessment methodologies, procedures, and
      results. It does not have a detrimental effect on survival.

PMID- 22361827
TI  - Symptom clusters and prognosis in advanced cancer.

PMID- 22361828
TI  - Breadth of the CD4+ T cell response to Anaplasma marginale VirB9-1, VirB9-2 and
      VirB10 and MHC class II DR and DQ restriction elements.
AB  - MHC class II molecules influence antigen-specific CD4+ T lymphocyte responses
      primed by immunization and infection. CD4+ T cell responses are important for
      controlling infection by many bacterial pathogens including Anaplasma marginale
      and are observed in cattle immunized with the protective A. marginale outer
      membrane (OM) vaccine. Immunogenic proteins that comprise the protective OM
      vaccine include type IV secretion system (T4SS) proteins VirB9-1, VirB9-2 and
      VirB10, candidates for inclusion in a multiepitope vaccine. Our goal was to
      determine the breadth of the VirB9-1, VirB9-2 and VirB10 T cell response and MHC
      class II restriction elements in six cattle with different MHC class II
      haplotypes defined by DRB3, DQA and DQB allele combinations for each animal.
      Overlapping peptides spanning each T4SS protein were tested in T cell
      proliferation assays with autologous antigen-presenting cells (APC) and
      artificial APC expressing combinations of bovine DR and DQ molecules. Twenty
      immunostimulatory peptides were identified; three representing two or more
      epitopes in VirB9-1, ten representing eight or more epitopes in VirB9-2 and seven
      representing seven or more epitopes in VirB10. Of the eight DRA/DRB3 molecules,
      four presented 15 peptides, which was biased as DRA/DRB3*1201 presented ten and
      DRA/DRB3*1101 presented four peptides. Four DQA/DQB molecules composed of two
      intrahaplotype and two interhaplotype pairs presented seven peptides, of which
      five were uniquely presented by DQ molecules. In addition, three functional mixed
      isotype (DQA/DRB3) restriction elements were identified. The immunogenicity and
      broad MHC class II presentation of multiple VirB9-1, VirB9-2 and VirB10 peptide
      epitopes justify their testing as a multiepitope vaccine against A. marginale.

PMID- 22361829
TI  - Eccentric rheometry for viscoelastic characterization of small, soft,
      anisotropic, and irregularly shaped biopolymer gels and tissue biopsies.
AB  - Quantification of the physical properties of tissue biopsies and cell-remodeled
      hydrogels is critical for understanding tissue development and pathophysiological
      tissue remodeling. However, due to the low modulus, small size, irregular shape,
      and anisotropy of samples from these materials, accurate viscoelastic
      characterization using standard rheometric methods is problematic. The goal of
      this work is to utilize image analysis to extend rotational rheometry to these
      samples. In this method, the sample is offset to increase the torque generated; a
      custom clear glass geometry, right angle prism, and camera are used to determine
      the exact shape and location of the sample relative to the axis of rotation for
      calculation of the sample shear modulus, G'. Values of G' for standard
      polydimethylsiloxane gels tested in centered and eccentric configurations were
      not statistically different (respectively 137 +/- 37 kPa and 126 +/- 8 kPa, p =
      0.58), indicating accuracy of the method. Additionally, G' values from circular
      and irregularly shaped collagen gels yielded equivalent results (31 +/- 1.8 Pa
      and 31 +/- 5.1 Pa, p = 0.29). A blood clot and a lipid plaque sample recovered
      from human patients (G' ~ 4 kPa) were successfully tested with this method
      demonstrating applicability to clinical diagnostics.

PMID- 22361831
TI  - Non-invasive estimation of cardiac output in mechanically ventilated patients: a
      prolonged expiration method.
AB  - A non-invasive method for the estimation of cardiac output in mechanically
      ventilated patients is described. The method is based on prolonged expiration,
      and relies on measurement of gas concentrations and flow rate. A pneumatic
      system, with an ad hoc designed orifice resistance, has been made and
      experimentally characterized to adapt the breathing circuit to this application.
      Cardiac output is calculated using two algorithms and the results are compared
      with the ones obtained by thermodilution. To this purpose, we prospectively
      enrolled twenty mechanically ventilated patients, who had undergone cardiac
      surgery, and both algorithms show good correlation with thermodilution (R > 0.8).
      The application of the first algorithm gave mean cardiac output values slightly
      lower than those obtained by thermodilution (-6%), while the application of the
      second algorithm gave higher values (+30%). Difference standard deviations
      between paired measurements is 0.72 L min(-1) for the first algorithm and 1.07 L
      min(-1) for the second one. Standard deviation obtained by the application of the
      first algorithm is slightly lower than those relative to other minimally invasive
      techniques. Through prolonged expiration, and standardization and automation of
      the procedure on mechanically ventilated patients, the proposed system allows to
      obtain a non-invasive estimation of cardiac output.

PMID- 22361833
TI  - Total laparoscopic hysterectomy without uterine manipulator at big uterus weight
      (>280 g).
AB  - METHODS: The retrospective study included the total laparoscopic hysterectomy
      without uterus manipulator at big uterus >280 g (Group A), proceeding the same
      technique as known to show feasibility and safety of its technique, compared with
      a randomized patient group of a uterus weight below 280 g (Group B). Statistical
      measurement was proceeded in typical clinical parameters. RESULTS: No statistical
      differences in age, body mass index, further abdominal surgery, blood loss, and
      hospital stay were observed. Operating time was significantly different favouring
      the uterus below 280 g (111.74 min Group A/90.68 min Group B). No increase in
      intra- or postoperative complications in both groups was observed. CONCLUSION:
      Total hysterectomy at big uterus (>280 g) is safe and feasible. Statistical
      analysis shows a significant shorter operating time only in one parameter (Group
      B). The technique of hysterectomy without uterus manipulator offers a surgical
      advancement also at vaginal stenosis, early staged cervix, or endometrial cancer
      and exhibits an opportunity for laparoscopic advancement in these cases too.

PMID- 22361834
TI  - Band edge modulated conjugated polymers for oxidation prevention.
AB  - The impact of electron transfer (ET) from a series of band edge modulated
      polymers to atmospheric oxygen is examined in connection with substrate oxidation
      prevention. Polymers with the highest occupied molecular orbital (HOMO) energy
      level below and above the oxygen energy level were tested and the former showed
      better efficiency. Furthermore, the oxidation prevention efficiency of a polymer
      with lower HOMO increased by two orders of magnitude, when the pores on the film
      were filled with spherical molecules, [6,6]-phenyl-C61-butyric acid methyl ester.
      We found that the polymer surface hydrophobicity has little or no influence on
      oxidation prevention. It is interesting to note that a polymer with a hole
      mobility of 8 * 10(-10) cm(2) V(-1) s(-1) showed a two-fold increase in oxidation
      prevention efficiency compared to a polymer with a hole mobility of 6 * 10(-5)
      cm(2) V(-1) s(-1). Over all, from the concerted approach, we conclude that a
      polymer devoid of pores with the HOMO energy level below oxygen and low charge
      carrier mobility is a suitable candidate for prevention of substrate
      oxidation/corrosion.

PMID- 22361835
TI  - Response time of nanofluidic electrochemical sensors.
AB  - Nanofluidic thin-layer cells count among the most sensitive electrochemical
      sensors built to date. Here we study both experimentally and theoretically the
      factors that limit the response time of these sensors. We find that the key
      limiting factor is reversible adsorption of the analyte molecules to the surfaces
      of the nanofluidic system, a direct consequence of its high surface-to-volume
      ratio. Our results suggest several means of improving the response time of the
      sensor, including optimizing the device geometry and tuning the electrode biasing
      scheme so as to minimize adsorption.

PMID- 22361832
TI  - Interacting partners of AMPA-type glutamate receptors.
AB  - Glutamate is the principal excitatory neurotransmitter in the brain. The alpha
      amino-3-hydroxyl-5-methyl-4-isoxazolepropionic (AMPA) receptors, as one of
      several types of endogenous ionotropic glutamate receptors, mediate the fast
      excitatory synaptic transmission that is essential for information processing and
      integration in the mammalian brain. Modifications of AMPA receptors are assumed
      to be the molecular basis underlying learning and memory, and impairments of AMPA
      receptors cause certain neurological diseases, including epilepsy, autism
      spectrum disorders, and Alzheimer's disease. Thus, extensive studies have been
      conducted, and these have revealed a complex protein-protein network controlling
      the expression, trafficking, and function of AMPA receptors in neurons. Here, we
      summarize the interacting partners of AMPA-type glutamate receptors and the
      functional implications of these interactions.

PMID- 22361836
TI  - Magnetization dynamics, throughput and energy dissipation in a universal
      multiferroic nanomagnetic logic gate with fan-in and fan-out.
AB  - The switching dynamics of a multiferroic nanomagnetic NAND gate with fan-in/fan
      out is simulated by solving the Landau-Lifshitz-Gilbert (LLG) equation while
      neglecting thermal fluctuation effects. The gate and logic wires are implemented
      with dipole-coupled two-phase (magnetostrictive/piezoelectric) multiferroic
      elements that are clocked with electrostatic potentials of ~50 mV applied to the
      piezoelectric layer generating 10.1 MPa stress in the magnetostrictive layers for
      switching. We show that a pipeline bit throughput rate of ~0.5 GHz is achievable
      with proper magnet layout and sinusoidal four-phase clocking. The gate operation
      is completed in 2 ns with a latency of 4 ns. The total (internal + external)
      energy dissipated for a single gate operation at this throughput rate is found to
      be only ~500 kT in the gate and ~1250 kT in the 12-magnet array comprising two
      input and two output wires for fan-in and fan-out. This makes it respectively
      three and five orders of magnitude more energy-efficient than complementary-metal
      oxide-semiconductor-transistor (CMOS)-based and spin-transfer-torque-driven
      nanomagnet-based NAND gates. Finally, we show that the dissipation in the
      external clocking circuit can always be reduced asymptotically to zero using
      increasingly slow adiabatic clocking, such as by designing the RC time constant
      to be three orders of magnitude smaller than the clocking period. However, the
      internal dissipation in the device must remain and cannot be eliminated if we
      want to perform fault-tolerant classical computing.

PMID- 22361837
TI  - Highlights in metastatic colorectal cancer from the American Society of Clinical
      Oncology Annual Meeting, June 3-7, 2011, Chicago, Illinois.

PMID- 22361839
TI  - Mesenchymal stem cell therapy following muscle trauma leads to improved muscular
      regeneration in both male and female rats.
AB  - BACKGROUND: Mesenchymal stem cell (MSC) therapy has the potential to enhance
      muscular regeneration. In previous publications, our group was able to show a
      dose-response relationship in female animals between the amount of transplanted
      cells and muscle force. The impact of sex on the regeneration of musculoskeletal
      injuries following MSC transplantation remains unclear. OBJECTIVE: We
      investigated histologic and biomechanical regeneration parameters in rats after
      autologous transplantation of MSCs. Our hypothesis was that female rats have
      greater muscle regeneration potential than male rats after autologous MSC
      transplantation. METHODS: Thirty-six Sprague-Dawley rats received an open crush
      trauma of the left soleus muscle. One week after trauma, 2.5 * 10(6) autologous
      MSCs, harvested from tibial biopsies, were transplanted locally (female, n = 9;
      male, n = 9). Control animals received saline solution (female, n = 9; male, n =
      9). Histologic analysis and biomechanical evaluation by in vivo muscle force
      measurement were performed 3 weeks after transplantation. RESULTS: MSC therapy
      improved the force of the injured soleus in male rats significantly (twitch:
      treated, 0.76 [0.51-1.15]; twitch: untreated, 0.45 [0.32-0.73] [P = 0.01];
      tetany: treated, 0.63 [0.4-1.21], tetany: untreated, 0.34 [0.16-0.48] [P =
      0.04]). Force measurements in females also revealed significant improvements
      (twitch: treated, 0.71 [0.38-0.96]; twitch: untreated, 0.36 [0.18-0.63] [P =
      0.005]; tetany: treated, 0.53 [0.21-0.68]; tetany: untreated, 0.27 [0.11-0.47] [P
      = 0.01]). The intersexual comparison of fast twitch and tetanic contraction
      forces revealed no significance (twitch, P = 0.55; tetany, P = 0.19). The
      histologic analysis showed no differences in the amount of fibrotic tissue (male,
      P = 0.9; female, P = 0.14) and the size of muscle area (male, P = 0.2; female, P
      = 0.56) following treatment. Male animals showed higher values for muscle area (P
      = 0.011) and less fibrosis (P = 0.028), independent of treatment. CONCLUSION: The
      outcome of skeletal muscle regeneration after injury can be improved in animals
      of both sexes with MSC transplantation.

PMID- 22361838
TI  - Postoperative estradiol levels associate with development of primary graft
      dysfunction in lung transplantation patients.
AB  - BACKGROUND: Primary graft dysfunction (PGD) frequently complicates lung
      transplantation in the immediate postoperative period. Both female gender and
      estradiol modulate the body's response to injury and can influence the rate of
      alveolar fluid clearance. OBJECTIVE: We hypothesized that female gender and
      higher estradiol levels would be associated with a lower risk of PGD after lung
      transplantation. METHODS: We measured plasma estradiol levels preoperatively, 6
      hours postoperatively, and 24 hours postoperatively in a cohort of 111 lung
      transplant recipients at 2 institutions. RESULTS: Mean age was 57 years (12.5)
      and 52% were female. Median postoperative estradiol level was 63.9 pg/mL
      (interquartile range, 28.8-154.3 pg/mL) in male and 65.1 pg/mL (interquartile
      range, 28.4-217.2 pg/mL) in female patients. Contrary to our hypothesis, higher
      estradiol levels at 24 hours were associated with an increased risk of PGD at 72
      hours in male patients (P = 0.001). This association was preserved when
      accounting for other factors known to be associated with PGD. However, there was
      no relationship between gender and risk of PGD or between estradiol levels and
      PGD in females. CONCLUSION: These findings suggest that there might be different
      biologic effects of estrogens in males and females, and highlight the importance
      of considering gender differences in future studies of PGD.

PMID- 22361840
TI  - Sex-dependent programming of glucose and fatty acid metabolism in mouse offspring
      by maternal protein restriction.
AB  - BACKGROUND: Nutritional conditions during fetal life influence the risk of the
      development of metabolic syndrome and cardiovascular diseases in adult life
      (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid
      metabolism are hallmarks of metabolic syndrome. OBJECTIVE: We aimed to establish
      a mouse model of metabolic programming focusing on the sex-specific effects of a
      maternal low-protein diet during gestation on glucose and lipid metabolism in the
      adult offspring. METHODS: Pregnant C57BL/6 mice received a control or a low
      protein diet (18% vs 9% casein) throughout gestation. Male and female offspring
      received a low-fat or a high-fat diet from 6 to 22 weeks of age. RESULTS:
      Maternal low-protein diet during gestation led to deteriorated insulin
      sensitivity on high-fat feeding in female offspring, as determined by biochemical
      and microarray analyses. Female offspring of control diet-fed dams were
      relatively resistant to high-fat diet-induced metabolic dysregulation. In
      contrast, maternal low-protein diet did not specifically affect the metabolic
      parameters addressed in male offspring. In males, the high-fat diet led to
      insulin insensitivity regardless of the diet of the dam. CONCLUSIONS: Our
      findings show that fetal malnutrition has a limited impact on male mouse
      offspring, yet it does influence the metabolic response to a high-fat diet in
      females. These findings may have implications for future early diagnostics in
      metabolic syndrome and for the development of sex-specific treatment regimens.

PMID- 22361841
TI  - In situ melanoma and palmar spiny hyperkeratoses: coincidence or paraneoplasia?

PMID- 22361842
TI  - Biological evaluation of a new family of aminosteroids that display a selective
      toxicity for various malignant cell lines.
AB  - This study investigated the antineoplasic potential of a new family of
      aminosteroids. The antiproliferative activity of seven 5alpha-androstane
      3alpha,17beta-diol derivatives selected from a screening study was measured on
      nine cancerous cell lines (HL-60, K-562, LNCaP, PC-3, Shionogi, MCF-7, MDA-MB
      231, BT-20, and OVCAR-3) and two normal cell lines (peripheral blood lymphocytes
      and WI-38). The aminosteroids efficiently inhibited the cell growth of seven
      cancer cell lines [inhibitory concentration (IC(50)) values=0.2-6.4 umol/l] and
      showed weak toxicity on normal cell lines. Two representative aminosteroids were
      tested and found to induce apoptosis and a G0/G1 cell cycle block in HL-60
      treated cells, but not terminal myeloid differentiation. By a nuclear morphology
      analysis with fluorescence microscopy, typical apoptotic morphological changes
      were exhibited by treated cells. One aminosteroid tested in vivo (xenograft
      model) reduced the breast cancer (MCF-7 cells) tumor growth induced in nude mice.
      Furthermore, the information gathered suggests that this family of aminosteroids
      induced growth inhibition cells by arresting the cell cycle and triggering
      apoptosis.

PMID- 22361844
TI  - SBA-15-functionalized sulfonic acid confined acidic ionic liquid: a powerful and
      water-tolerant catalyst for solvent-free esterifications.
AB  - Incorporating a hydrophobic Bronsted acid ionic liquid (HBAIL) inside the
      nanospaces of SBA-15-Pr-SO(3)H led to a hydrophobic super Bronsted acid catalyst,
      which showed excellent catalytic performance in direct esterification of alcohols
      and carboxylic acids at ambient temperature under solvent-free conditions.

PMID- 22361843
TI  - Inflammation in neurological and psychiatric diseases.
AB  - In recent years, compelling evidence suggests that inflammation plays a critical
      role in the pathology of a vast number of neurological diseases such as stroke,
      Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis as
      well as neuropsychiatric diseases such as major depression and schizophrenia.
      Despite emerging evidence in human and animal models alike, modulating
      inflammatory responses have yet to be proven as an effective treatment to prevent
      or delay the progression of these diseases. The primary focus of this special
      edition is to highlight some of our current findings on the complexities of
      targeting neuroinflammation as a novel therapy, and its role in neurological and
      psychiatric disorders.

PMID- 22361845
TI  - Non-infectious orbital vasculitides.
AB  - Non-infectious vasculitides comprise a large number of diseases. Many of these
      diseases can cause inflammation within the orbit and a clinical presentation,
      which mimics numerous other processes. Orbital disease can often be the initial
      presentation of a systemic process and early diagnosis can help prevent long
      term, potentially fatal consequences. The evaluation and treatment of non
      infectious orbital vasculitides are often complicated and require a thorough
      understanding of the disease and underlying systemic associations. The long-term
      prognosis visually and systemically must be weighed against the risks and
      benefits of the treatment regimen. A large variety of corticosteroid formulations
      currently exist and are the mainstay of initial treatment. Traditional steroid
      sparing immunosuppressive agents are also an important arsenal against these
      vasculitides. Recently, a new class of drugs called biologics, which target the
      various mediators of the inflammation cascade, may potentially provide more
      effective and less toxic treatment. This review aims to synthesize the current
      literature on non-infectious orbital vasculitides.

PMID- 22361846
TI  - Comment on 'Idiopathic uveal effusion syndrome causing unilateral acute angle
      closure in a pseudophakic patient'.

PMID- 22361847
TI  - Clinical pattern of ocular toxoplasmosis treated in a referral centre in Serbia.
AB  - PURPOSE: To analyze the clinical pattern of ocular toxoplasmosis (OT) in a
      referral centre in Serbia. PATIENTS AND METHODS: The medical records of
      consecutive patients admitted for OT to the single referral centre for uveitis in
      Serbia between 2006 and 2010 were retrospectively analyzed. OT was diagnosed on
      the basis of typical fundus lesions and positive serology for Toxoplasma.
      RESULTS: In a total of 457 uveitis patients, OT was the third leading cause, with
      59 patients (12.9%). Most OT cases (73%) were monocular. An active primary
      retinal lesion was observed in 36% and recurrent OT in 64% patients. Localization
      of lesions was central/paracentral (44%), juxtapapillar (27%), peripheral (19%),
      and multifocal (10%). Other ocular manifestations of inflammation included
      vitritis (44%), anterior uveitis (19%), and retinal vasculitis (10%).
      Complications included choroidal neovascularization in two and exudative retinal
      detachment with cataract, glaucoma, and cystoid macular oedema in one patient
      each. The detection of Toxoplasma-specific IgM antibodies in a single patient
      indicates a low rate of OT concomitant with acute infection. After treatment, the
      mean best-corrected visual acuity (BCVA) increased significantly. However, 14
      (24%) patients ended up legally blind in the affected eye, of which 2 (3%) with
      bilateral blindness, all with a very poor BCVA (0.047 +/- 0.055) at presentation.
      Visual impairment and treatment outcome were both associated with central
      localization of lesions (P<0.0001 and P=0.006, respectively). CONCLUSION: OT is a
      significant cause of posterior uveitis in Serbia. Patients should be aware of the
      recurring nature of OT and react immediately if symptoms occur.

PMID- 22361848
TI  - The sources of pain during phacoemulsification using topical anesthesia.

PMID- 22361849
TI  - Enzymatic mechanisms regulating protein S-nitrosylation: implications in health
      and disease.
AB  - Nitric oxide participates in cellular signal transduction largely through S
      nitrosylation of allosteric and active-site cysteine thiols within proteins,
      forming S-nitroso-proteins (SNO-proteins). S-nitrosylation of proteins has been
      demonstrated to affect a broad range of functional parameters including enzymatic
      activity, subcellular localization, protein-protein interactions, and protein
      stability. Analogous to other ubiquitous posttranslational modifications that are
      regulated enzymatically, including phosphorylation and ubiquitinylation,
      accumulating evidence suggests the existence of enzymatic mechanisms for
      regulating protein S-nitrosylation. In particular, studies have led to the
      identification of multiple enzymes (nitrosylases and denitrosylases) that
      participate in targeted S-nitrosylation or denitrosylation of proteins in
      physiological settings. Nitrosylases are best characterized in the context of
      transnitrosylation in which a SNO-protein transfers an NO group to an acceptor
      protein (Cys-to-Cys transfer), but examples of transnitrosylation catalyzed by
      metalloproteins (Metal-to-Cys transfer) also exist. By contrast, denitrosylases
      remove the NO group from SNO-proteins, ultimately using reducing equivalents
      derived from NADH or NADPH. Here, we focus on the recent discoveries of
      nitrosylases and denitrosylases and the notion that their aberrant activities may
      play roles in health and disease.

PMID- 22361850
TI  - Ultrasonographic findings in cattle and buffaloes with chronic hepatic
      fascioliosis.
AB  - The purpose of this study was to characterize the ultrasonographic findings in
      cattle and buffaloes with chronic hepatic fascioliosis. To the best of the
      author's knowledge, this report is the first to document ultrasonographic
      findings in buffaloes with chronic hepatic fascioliosis. Ultrasonographic
      findings included distended gallbladders with either homogenous or heterogeneous
      contents, edema of the gallbladder walls, which ranged from mild or moderate to
      severe and bile duct mineralization. In 78% of the buffaloes, there was an
      ultrasonographic picture of hepatic fibrosis in which heterogeneous and
      hyperechogenic hepatic parenchymas with multiple echogenic foci were imaged.
      Other ultrasonographic findings included peritoneal, pleural and pericardial
      effusions. Two cows and one buffalo were slaughtered and examined postmortem.
      Hence, it was possible to verify distended gallbladders, edema of the gallbladder
      wall, calcified bile ducts, cholestasis and hepatic fibrosis by using
      ultrasonography in the cows and buffaloes with chronic hepatic fascioliosis. The
      procedure offers a useful supplement to clinical, hematological and biochemical
      examinations on the diagnosis of this condition.

PMID- 22361851
TI  - Pathophysiologic mechanisms of calcific aortic stenosis.
AB  - Calcific aortic stenosis (CAS) comprises the leading indication for valve
      replacement in the Western world. Until recently, progressive calcification was
      considered to be a passive process. Emerging evidence, however, suggests that
      degenerative aortic stenosis constitutes an active process involving stimulation
      of several pathophysiologic pathways such as inflammation and osteogenesis. In
      addition, CAS and atherosclerosis share common features regarding histopathology
      of lesions. These novel data raise a new perspective on the prevention and
      treatment of disease. The current article reviews the most important
      pathophysiologic mechanisms of senile aortic stenosis.

PMID- 22361853
TI  - Utilization of Anabaena sp. in CO2 removal processes: modelling of biomass,
      exopolysaccharides productivities and CO2 fixation rate.
AB  - This paper focuses on modelling the growth rate and exopolysaccharides production
      of Anabaena sp. ATCC 33047, to be used in carbon dioxide removal and biofuels
      production. For this, the influence of dilution rate, irradiance and aeration
      rate on the biomass and exopolysaccharides productivity, as well as on the CO(2)
      fixation rate, have been studied. The productivity of the cultures was maximum at
      the highest irradiance and dilution rate assayed, resulting to 0.5 g(bio) l(-1)
      day(-1) and 0.2 g(eps) l(-1) day(-1), and the CO(2) fixation rate measured was
      1.0 gCO(2) l(-1) day(-1). The results showed that although Anabaena sp. was
      partially photo-inhibited at irradiances higher than 1,300 MUE m(-2) s(-1), its
      growth rate increases hyperbolically with the average irradiance inside the
      culture, and so does the specific exopolysaccharides production rate. The latter,
      on the other hand, decreases under high external irradiances, indicating that the
      exopolysaccharides metabolism hindered by photo-damage. Mathematical models that
      consider these phenomena have been proposed. Regarding aeration, the yield of the
      cultures decreased at rates over 0.5 v/v/min or when shear rates were higher than
      60 s(-1), demonstrating the existence of thus existence of stress damage by
      aeration. The behaviour of the cultures has been verified outdoors in a pilot
      scale airlift tubular photobioreactor. From this study it is concluded that
      Anabaena sp. is highly recommended to transform CO(2) into valuable products as
      has been proved capable of metabolizing carbon dioxide at rates of 1.2 gCO(2) l(
      1) day(-1) outdoors. The adequacy of the proposed equations is demonstrated,
      resulting to a useful tool in the design and operation of photobioreactors using
      this strain.

PMID- 22361854
TI  - Enhanced production of 2,3-butanediol by engineered Bacillus subtilis.
AB  - Production of 2,3-butanediol by Bacillus subtilis takes place in late-log or
      stationary phase, depending on the expression of bdhA gene encoding acetoin
      reductase, which converts acetoin to 2,3-butanediol. The present work focuses on
      the development of a strain of B. subtilis for enhanced production of 2,3
      butanediol in early log phase of growth cycle. For this, the bdhA gene was
      expressed under the control of P( alsSD ) promoter of AlsSD operon for acetoin
      fermentation which served the substrate for 2,3-butanediol production. Addition
      of acetic acid in the medium induced the production of 2,3-butanediol by 2-fold.
      Two-step aerobic-anaerobic fermentation further enhanced 2,3-butanediol
      production by 4-fold in comparison to the control parental strain. Thus, addition
      of acetic acid and low dissolved oxygen in the medium are involved in activation
      of bdhA gene expression from P( alsSD ) promoter in early log phase. Under the
      conditions tested in this work, the maximum production of 2,3-butanediol, 2.1 g/l
      from 10 g/l glucose, was obtained at 24 h. Furthermore, under the optimized
      microaerophilic condition, the production of 2,3-butanediol improved up to 6.1
      g/l and overall productivity increased by 6.7-fold to 0.4 g/l h in the engineered
      strain compared to that in the parental control.

PMID- 22361852
TI  - Protein homeostasis, aging and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one key medical challenge of the aging society and
      despite a great amount of effort and a huge collection of acquired data on
      molecular mechanisms that are associated with the onset and progression of this
      devastating disorder, no causal therapy is in sight. The two main hypotheses of
      AD, the amyloid cascade hypothesis and the Tau hypothesis, are still in the focus
      of AD research. With aging as the accepted main risk factor of the most important
      non familial and late onset sporadic forms of AD, it is now mandatory to discuss
      more intensively aspects of cellular aging and aging biochemistry and its impact
      on neurodegeneration. Since aging is accompanied by changes in cellular protein
      homeostasis and an increasing demand for protein degradation, aspects of protein
      folding, misfolding, refolding and, importantly, protein degradation need to be
      linked to AD pathogenesis. This is the purpose of this short review.

PMID- 22361856
TI  - Production of lipids in 10 strains of Chlorella and Parachlorella, and enhanced
      lipid productivity in Chlorella vulgaris.
AB  - We tested 10 different Chlorella and Parachlorella strains under lipid induction
      growth conditions in autotrophic laboratory cultures. Between tested strains,
      substantial differences in both biomass and lipid productivity as well as in the
      final content of lipids were found. The most productive strain (Chlorella
      vulgaris CCALA 256) was subsequently studied in detail. The availability of
      nitrates and/or phosphates strongly influenced growth and accumulation of lipids
      in cells by affecting cell division. Nutrient limitation substantially enhanced
      lipid productivity up to a maximal value of 1.5 g l(-1) day(-1). We also
      demonstrated the production of lipids through large-scale cultivation of C.
      vulgaris in a thin layer photobioreactor, even under suboptimal conditions. After
      8 days of cultivation, maximal lipid productivity was 0.33 g l(-1) day(-1),
      biomass density was 5.7 g l(-1) dry weight and total lipid content was more than
      30% dry weight. C. vulgaris lipids comprise fatty acids with a relatively high
      degree of saturation compared with canola oil offering a possible alternative to
      the use of higher plant oils.

PMID- 22361855
TI  - Microbial community structure elucidates performance of Glyceria maxima plant
      microbial fuel cell.
AB  - The plant microbial fuel cell (PMFC) is a technology in which living plant roots
      provide electron donor, via rhizodeposition, to a mixed microbial community to
      generate electricity in a microbial fuel cell. Analysis and localisation of the
      microbial community is necessary for gaining insight into the competition for
      electron donor in a PMFC. This paper characterises the anode-rhizosphere
      bacterial community of a Glyceria maxima (reed mannagrass) PMFC.
      Electrochemically active bacteria (EAB) were located on the root surfaces, but
      they were more abundant colonising the graphite granular electrode. Anaerobic
      cellulolytic bacteria dominated the area where most of the EAB were found,
      indicating that the current was probably generated via the hydrolysis of
      cellulose. Due to the presence of oxygen and nitrate, short-chain fatty acid
      utilising denitrifiers were the major competitors for the electron donor. Acetate
      utilising methanogens played a minor role in the competition for electron donor,
      probably due to the availability of graphite granules as electron acceptors.

PMID- 22361857
TI  - Phylogenetic analysis of genes involved in mycosporine-like amino acid
      biosynthesis in symbiotic dinoflagellates.
AB  - Mycosporine-like amino acids (MAAs) are multifunctional secondary metabolites
      involved in photoprotection in many marine organisms. As well as having broad
      ultraviolet (UV) absorption spectra (310-362 nm), these biological sunscreens are
      also involved in the prevention of oxidative stress. More than 20 different MAAs
      have been discovered so far, characterized by distinctive chemical structures and
      a broad ecological distribution. Additionally, UV-screening MAA metabolites have
      been investigated and used in biotechnology and cosmetics. The biosynthesis of
      MAAs has been suggested to occur via either the shikimate or pentose phosphate
      pathways. Despite their wide distribution in marine and freshwater species and
      also the commercial application in cosmetic products, there are still a number of
      uncertainties regarding the genetic, biochemical, and evolutionary origin of
      MAAs. Here, using a transcriptome-mining approach, we identify the gene
      counterparts from the shikimate or pentose phosphate pathway involved in MAA
      biosynthesis within the sequences of the reef-building coral symbiotic
      dinoflagellates (genus Symbiodinium). We also report the highly similar sequences
      of genes from the proposed MAA biosynthetic pathway involved in the metabolism of
      4-deoxygadusol (direct MAA precursor) in various Symbiodinium strains confirming
      their algal origin and conserved nature. Finally, we reveal the separate identity
      of two O-methyltransferase genes, possibly involved in MAA biosynthesis, as well
      as nonribosomal peptide synthetase and adenosine triphosphate grasp homologs in
      symbiotic dinoflagellates. This study provides a biochemical and phylogenetic
      overview of the genes from the proposed MAA biosynthetic pathway with a focus on
      coral endosymbionts.

PMID- 22361858
TI  - The EmhABC efflux pump decreases the efficiency of phenanthrene biodegradation by
      Pseudomonas fluorescens strain LP6a.
AB  - Pseudomonas fluorescens strain LP6a, designated here as strain WEN (wild-type PAH
      catabolism, efflux positive), utilizes the polycyclic aromatic hydrocarbon
      phenanthrene as a carbon source but also extrudes it into the extracellular
      medium using the efflux pump EmhABC. Because phenanthrene is considered a
      nontoxic carbon source for P. fluorescens WEP, its energy-dependent efflux seems
      counter-productive. We hypothesized that the efflux of phenanthrene would
      decrease the efficiency of its biodegradation. Indeed, an emhB disruptant strain,
      wild-type PAH catabolism, efflux negative (WEN), biodegraded 44% more
      phenanthrene than its parent strain WEP during a 6-day incubation. To determine
      whether efflux affected the degree of oxidation of phenanthrene, we quantified
      the conversion of 14C-phenanthrene to radiolabeled polar metabolites and 14CO2.
      The emhB- WEN strain produced approximately twice as much 14CO2 and radiolabeled
      water-soluble metabolites as the WEP strain. In contrast, the mineralization of
      14C-glucose, which is not a known EmhB efflux substrate, was equivalent in both
      strains. An early open-ring metabolite of phenanthrene, trans-4-(1-hydroxynaphth
      2-yl)-2-oxo-3-butenoic acid, also was found to be a substrate of the EmhABC pump
      and accumulated in the supernatant of WEP but not WEN cultures. The analogous
      open-ring metabolite of dibenzothiophene, a heterocyclic analog of phenanthrene,
      was extruded by EmhABC plus a putative alternative efflux pump, whereas the end
      product 3-hydroxy-2-formylbenzothiophene was not actively extruded from either
      WEP or WEN cells. These results indicate that the active efflux of phenanthrene
      and its early metabolite(s) decreases the efficiency of phenanthrene degradation
      by the WEP strain. This activity has implications for the bioremediation and
      biocatalytic transformation of polycyclic aromatic hydrocarbons and heterocycles.

PMID- 22361859
TI  - Patterns of carbohydrate and fatty acid changes under nitrogen starvation in the
      microalgae Haematococcus pluvialis and Nannochloropsis sp.
AB  - The aim of this research was to study the impact of nitrogen starvation on the
      production of two major secondary metabolites, fatty acids and carbohydrates, in
      two microalgae: Nannochloropsis sp. and Haematococcus pluvialis. The major
      response to nitrogen starvation in both algae occurred within the first 2 days,
      accompanied by a sharp reduction in chlorophyll content. However, the pattern of
      the response differed between the two microalgae. In H. pluvialis, the first
      response to nitrogen starvation was intensive production of carbohydrates,
      accumulating to up to 63% of dry weight by day 1; on day 2, the total
      carbohydrate content decreased and was partially degraded, possibly to support
      fatty acid synthesis. Under these conditions, H. pluvialis accumulated up to 35%
      total fatty acids in the biomass. In Nannochloropsis sp., the immediate and major
      response, which was maintained throughout the entire period of exposure to
      stress, was production of fatty acids, accumulating up to 50% of dry weight,
      while carbohydrate content in the biomass remained stable at 18%. In addition, we
      tested the effect of the lipid-synthesis inhibitor sesamol, known to inhibit
      malic enzyme, on the balance between total fatty acid and carbohydrate contents
      in H. pluvialis and Nannochloropsis sp. In both cultures, sesamol inhibited fatty
      acid accumulation, but the carbohydrate content was reduced as well, albeit to a
      lesser extent. These findings demonstrate the complexity of the stress-response
      and the potential link between fatty acid and carbohydrate synthesis.

PMID- 22361860
TI  - Asymmetric synthesis of (R)-1,3-butanediol from 4-hydroxy-2-butanone by a newly
      isolated strain Candida krusei ZJB-09162.
AB  - Biocatalytic asymmetric preparation of (R)-1,3-butanediol has been attracting
      much attention in pharmaceuticals industry. A new ideal strain, ZJB-09162, which
      exhibited high reduction activity and excellent (R)-stereospecificity towards 4
      hydroxy-2-butanone, has been successfully isolated from soil samples. Based on
      morphology, physiological tests (API 20 C AUX), and 5.8S-ITS sequence, the
      isolate was identified as Candida krusei. Kinetic characterization demonstrated
      that carbonyl reductase from C. krusei ZJB-09162 preferred NADH to NADPH as
      cofactor, indicating it might be a new carbonyl reductase. (R)-1,3-Butanediol was
      produced in 19.8 g/L, 96.6% conversion, and 99.0% ee at optimal pH 8.5, 35 
      degrees C with a 2:1 molar ratio of glucose to 4H2B. In order to achieve higher
      product titer, the substrate loading was optimized in fixed catalysts and fixed
      substrate/catalysts ratio mode. The bioreduction of 4-hydroxy-2-butanone at a
      concentration of 45.0 g/L gave (R)-1,3-butanediol in 38.7 g/L and 83.9%
      conversion. Therefore, C. krusei ZJB-09162 was, for the first time, proven to be
      a promising biocatalyst for enzymatic preparation of (R)-1,3-butanediol.

PMID- 22361861
TI  - 4,6-alpha-Glucanotransferase activity occurs more widespread in Lactobacillus
      strains and constitutes a separate GH70 subfamily.
AB  - Family 70 glycoside hydrolase glucansucrase enzymes exclusively occur in lactic
      acid bacteria and synthesize a wide range of alpha-D-glucan (abbreviated as alpha
      glucan) oligo- and polysaccharides. Of the 47 characterized GH70 enzymes, 46 use
      sucrose as glucose donor. A single GH70 enzyme was recently found to be inactive
      with sucrose and to utilize maltooligosaccharides [(1->4)-alpha-D
      glucooligosaccharides] as glucose donor substrates for alpha-glucan synthesis,
      acting as a 4,6-alpha-glucanotransferase (4,6-alphaGT) enzyme. Here, we report
      the characterization of two further GH70 4,6-alphaGT enzymes, i.e., from
      Lactobacillus reuteri strains DSM 20016 and ML1, which use maltooligosaccharides
      as glucose donor. Both enzymes cleave alpha1->4 glycosidic linkages and add the
      released glucose moieties one by one to the non-reducing end of growing linear
      alpha-glucan chains via alpha1->6 glycosidic linkages (alpha1->4 to alpha1->6
      transfer activity). In this way, they convert pure maltooligosaccharide
      substrates into linear alpha-glucan product mixtures with about 50% alpha1->6
      glycosidic bonds (isomalto/maltooligosaccharides). These new alpha-glucan
      products may provide an exciting type of carbohydrate for the food industry. The
      results show that 4,6-alphaGTs occur more widespread in family GH70 and can be
      considered as a GH70 subfamily. Sequence analysis allowed identification of amino
      acid residues in acceptor substrate binding subsites +1 and +2, differing between
      GH70 GTF and 4,6-alphaGT enzymes.

PMID- 22361862
TI  - Comparison of endoscopic papillary large balloon dilation and endoscopic
      sphincterotomy for retrieval of choledocholithiasis: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Endoscopic sphincterotomy (EST) is the most frequently used technique
      for removal of stones from the bile duct. In recent years, endoscopic papillary
      large balloon dilation (EPLBD) has been shown to be a safe and effective
      technique for the removal of large or difficult common bile duct stones. However,
      comparison of EPLBD and EST for effectiveness in bile duct stone removal has
      given inconsistent results. The present meta-analysis was carried out to compare
      the effect of EPLBD and EST in retrieval of choledocholithiasis. METHODS: A
      literature search was performed using Medline, PubMed, EMBase and the Cochrane
      Central Register of Controlled Trials (CENTRAL) for relevant articles published
      in English. A meta-analysis was performed on the retrieved studies. RESULTS:
      Seven randomized controlled trials and 790 patients were involved. EPLBD compared
      with EST resulted in similar outcomes for overall successful clearance rates of
      bile duct stones (97.35 vs. 96.35%, OR 1.28, 95% CI 0.58-2.82, P = 0.54), stone
      clearance in the first ERCP session (87.87 vs. 84.15%, OR 1.31, 95% CI 0.81-2.11,
      P = 0.21) and removal of large sized stones (OR 1.08, 95% CI 0.21-5.64, P =
      0.49). EPLBD performed with either a short or a long ballooning time did not
      increase the bile duct stone clearance rate. EPLBD decreased overall usage of
      mechanical lithotripsy in the bile duct stone removal process (OR 0.51, 95% CI
      0.30-0.86, P = 0.01). However, no significant difference was found between EPLBD
      and EST in the use of mechanical lithotripsy for the removal of large sized
      stones (OR 0.67, 95% CI 0.34-1.28, P = 0.22). Compared with EST, EPLBD did not
      show a short ERCP duration (WMD -0.75, 95% CI -1.57 to 0.08, P = 0.08). EPLBD was
      associated with fewer overall complications than EST (5.8 vs. 13.1%, OR 0.41, 95%
      CI 0.24-0.68, P = 0.0007). Hemorrhage occurred less frequently with EPLBD than
      with EST (OR 0.15, 95% CI 0.04-0.50, P = 0.002). There was no significant
      difference in post-ERCP pancreatitis, perforation and cholangitis. CONCLUSIONS:
      EPLBD is an effective and safe method for the removal of large or difficult
      common bile stones. EPLBD should be considered as an alternative to EST for
      patients in whom EST could not be routinely performed. Based on EPLBD causing
      fewer cases of hemorrhaging, EPLBD is also recommended for removal of large or
      difficult common bile duct stones in patients with an underlying coagulopathy or
      need for anticoagulation following ERCP. The long-term prognosis of EPLBD need to
      be further investigated.

PMID- 22361863
TI  - High TrkB expression levels are associated with poor prognosis and EMT induction
      in colorectal cancer cells.
AB  - BACKGROUND: The neurotrophic receptor tropomyosin related kinase (TrkB) is
      associated with tumor progression in neuroblastoma and certain human
      malignancies. Recent reports indicate TrkB may participate in the epithelial
      mesenchymal transition (EMT). This study investigates whether TrkB expression is
      associated with the clinical outcome of colorectal cancer (CRC) patients and
      whether TrkB induces EMT in CRC cells. METHODS: TrkB and E-cadherin expression in
      surgical tissue samples and clinicopathological data from 102 CRC patients were
      analyzed by real-time polymerase chain reaction and immunohistochemistry. The
      biological role of TrkB in CRC was analyzed using RNA interference against TrkB
      in the CRC cell line SW480 to assess tumor progression and the correlation
      between TrkB and E-cadherin expression. RESULTS: Patients with high TrkB mRNA
      expression in clinical samples had a significantly poorer prognosis relative to
      those with low TrkB levels (p = 0.03). TrkB was inversely correlated with E
      cadherin at both the mRNA and protein levels. In vitro, cell proliferation (p =
      0.02), migration (p < 0.001), and invasion (p < 0.001) were significantly
      inhibited by TrkB knockdown while the anoikis rate increased in TrkB siRNA
      transfected cells compared to control siRNA. Interestingly, E-cadherin expression
      in TrkB siRNA-transfected cells was higher than in control cells and vimentin was
      lower conversely. CONCLUSIONS: High TrkB expression is associated with poor
      prognosis in CRC patients and enhanced malignant potential in terms of
      proliferation, migration, invasion, and anoikis inhibition in CRC cells. These
      results indicate TrkB could induce EMT and play an important role in CRC
      progression to metastasis.

PMID- 22361864
TI  - Alternative procedure to shorten rectal barostat procedure for the assessment of
      rectal compliance and visceral perception: a feasibility study.
AB  - BACKGROUND: Barostat methodology is widely used for assessing visceral
      perception. Different barostat protocols are described with respect to the
      measurement of rectal compliance and visceral perception. The choice of protocols
      affects the duration, which is normally 60-90 min, and accuracy of the procedure.
      This study aimed to shorten the procedure by using the semi-random distension
      protocol for both compliance and visceral perception measurement and a correction
      based on rectal capacity (RC) instead of minimal distension pressure (MDP).
      METHODS: Twelve irritable bowel syndrome (IBS) patients (7 females) and 11
      healthy controls (8 females) underwent a barostat procedure. Compliance was
      determined during both a staircase distension and a semi-random protocol.
      Visceral perception data were compared as a function of pressure or relative
      volume, corrected for MDP or RC, respectively. RESULTS: Compliance measurement
      using the semi-random protocol instead of the staircase distension protocol
      resulted in an overestimation in healthy volunteers, but not in IBS patients. The
      overall conclusion that IBS patients had a lower compliance compared to controls
      was not different between protocols. Data presentation of the visceral perception
      scores as a function of corrected volume instead of pressures corrected for MDP
      did not alter the conclusion that sensation scores in IBS patients were higher as
      compared to healthy controls. CONCLUSIONS: This study showed that barostat
      procedures may be shortened by approximately 20 min, without losing the ability
      to discriminate between healthy controls and IBS patients. A correction for RC
      instead of MDP may improve the accuracy of the procedure.

PMID- 22361866
TI  - Advancing the science of nursing, improving the quality of care.
AB  - The director of the Magnet Recognition Program provides a comprehensive look at
      the Magnet model component new knowledge, innovation, and improvements. This
      article examines Magnet organizations' responsibility to advance evidence-based
      practice, improve quality, and develop new models of care. It includes exemplars
      of innovative contributions from Magnet organizations around the country.

PMID- 22361865
TI  - Long-term efficacy of interferon therapy in patients with chronic hepatitis B
      virus infection in Japan.
AB  - BACKGROUND: Few studies have investigated the long-term effects of interferon
      (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we
      investigated the efficacy of and predictors of response to IFN therapy in CHB
      patients. METHODS: We analyzed data for 615 Japanese CHB patients (hepatitis B e
      antigen [HBeAg]-positive 414, HBeAg-negative 201) treated with IFN, and conducted
      follow up for a median duration of 8.1 years (range 0.5-23.2). Responders were
      defined as patients who showed continuously normalized alanine transaminase (ALT)
      levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels at 6 months
      post-treatment or for a span of more than 6 months until each test point at 1, 3,
      5, and 10 years. RESULTS: The IFN response rates of all patients were 21, 18, 21,
      23, and 25% at 6 months and 1, 3, 5, and 10 years, respectively. On multivariate
      analysis, significant determinants of the outcome of IFN therapy were as follows:
      at 6 months and 1 year, young age, low HBV DNA levels, and long duration of
      treatment; at 3 years, long duration of treatment, young age, and high level of
      albumin; at 5 years, high level of albumin, female, and pretreated with IFN; and
      at 10 years, HBeAg-negative. Sixty-nine of the 615 patients (11%) achieved
      seroclearance of hepatitis B surface antigen (HBsAg). On multivariate analysis,
      age >=30 years, HBV genotype A, and male were all independent factors predicting
      the achievement of HBsAg seroclearance. CONCLUSION: HBeAg, HBV DNA level, age,
      sex, albumin, duration of treatment, pretreatment with IFN, and HBV genotype were
      important factors in determining long-term response to IFN therapy.

PMID- 22361867
TI  - Same-handed patient room configurations: anecdotal and empirical evidence.
AB  - Same-handed patient room design has been noted to improve patient and nurse
      outcomes. This facility design article expands the knowledge of nurse leaders and
      their competencies in health facility design, enabling them to take leadership
      roles in design efforts. This article explores assumptions and anecdotal and
      empirical evidence about the same-handed room design concept.

PMID- 22361868
TI  - Leading a highly visible hospital through a serious reportable event.
AB  - Most preventable adverse events result from systemic causes, not human error. The
      senior vice president for patient care/chief nurse at a leading hospital recounts
      the unnecessary death of a patient and the investigation that followed. Citing
      the critical importance of a "just culture," this case study offers a blueprint
      for managing a serious reportable event.

PMID- 22361869
TI  - Oregon nurse staffing law: is it working?
AB  - In 2001, Oregon enacted a law mandating the creation of hospital nurse staffing
      committees to oversee staffing in acute care hospitals. The study design is a
      descriptive case study (qualitative method) using semistructured interviews and
      focus groups to assess the law requiring hospital nurse staffing committees to
      monitor nurse staffing in Oregon. One significant theme of the study was the wide
      variation among facilities in the way the staffing legislation is viewed,
      interpreted, understood, appreciated, and implemented. Another was that the chief
      nursing officer's view of the legislation tended to be the prevailing view
      expressed by the managers and staff nurses from those same organizations. A
      significant difference between a functional versus nonfunctional committee was
      whether the chief nurse viewed the legislation in a positive way and was using
      the legislation to enhance his/her work.

PMID- 22361870
TI  - A nursing career lattice pilot program to promote racial/ethnic diversity in the
      nursing workforce.
AB  - The nursing career lattice program (NCLP) at Children's Hospital Boston has
      provided employees with social, educational, and financial assistance as they
      begin or advance their nursing careers. At the conclusion of a pilot phase, 35%
      of employees in the NCLP were enrolled in nursing school and 15% completed
      nursing school. The NCLP exemplifies how a workforce diversity initiative can
      lead to outcomes that support and sustain a culture rich in diversity and
      perpetuate excellence in nursing in one organization.

PMID- 22361871
TI  - Maximizing caring relationships between nursing assistants and patients: care
      partners.
AB  - Certified nursing assistants (CNAs) are an integral part of the care team in most
      hospitals. The chief nursing officer at a community hospital in Florida developed
      a program of communication, education, and accountability to highlight the role
      of the CNA as a team member. This easy-to-implement initiative resulted in
      increased understanding about the CNA role in delivering high-quality patient
      care and increases in patient satisfaction with responsiveness of staff to call
      lights.

PMID- 22361872
TI  - Impact of healthy work environments and multistage nurse residency programs on
      retention of newly licensed RNs.
AB  - The objective of the study was to examine effects of nurse-confirmed healthy unit
      work environments and multistage nurse residency programs (NRPs) on retention
      rates of newly licensed RNs (NLRNs). Establishing a culture of retention and
      healthy clinical nurse practice environments are two major challenges confronting
      nurse leaders today. Nurse residency programs are a major component of NLRN work
      environments and have been shown to be effective in abating nurse turnover.
      Sample for this study consisted of 5,316 new graduates in initial RN roles in 28
      Magnet(r) hospitals. There were no differences in retention rates by education or
      patient population on clinical unit. NLRN retention rate was higher in community
      than in academic hospitals. More than half of NLRNs were placed on units with
      very healthy work environments. Newly licensed RNs on units with work
      environments needing improvement resigned at a significantly higher rate than did
      other NLRNs. The quality of clinical unit work environments is the most important
      factor in NLRN retention.

PMID- 22361873
TI  - Patients' perceptions of patient care providers with tattoos and/or body
      piercings.
AB  - OBJECTIVE: This study evaluated patients' perceptions of patient care providers
      with visible tattoos and/or body piercings. BACKGROUND: As tattooing and body
      piercing are increasingly popular, research that informs nursing administrators
      regarding policies on patient care providers having visible tattoos and body
      piercings is warranted. METHODS: A total of 150 hospitalized adult patients
      compared pictures of male and female patient care providers in uniform with and
      without tattoos and/or nonearlobe body piercings. RESULTS: Patient care providers
      with visible tattoos and/or body piercings were not perceived by patients in this
      study as more caring, confident, reliable, attentive, cooperative, professional,
      efficient, or approachable than nontattooed or nonpierced providers. Tattooed
      female providers were perceived as less professional than male providers with
      similar tattoos. Female providers with piercings were perceived as less
      confident, professional, efficient, and approachable than nonpierced female
      providers. CONCLUSIONS: Nursing administrators should develop and/or evaluate
      policies regarding patient care providers with visible tattoos and/or body
      piercings.

PMID- 22361874
TI  - Strengthening frontline nurse investment in organizational goals.
AB  - Frontline nurses are foundational to any organizational goal concerning patient
      care. In addition, healthcare delivery reform has supported the formalization of
      specific goals that hospitals must advance to stay financially viable and to
      deliver high-quality care. As a result, goals for frontline staff are
      continuously evolving. Frontline nurses must demonstrate a commitment not only to
      delivering excellent patient care but also to advancing larger institutional
      performance. The authors discuss a framework for nurse executives to help
      organizations achieve enhanced nurse investment in organizational goals.

PMID- 22361875
TI  - Developing and implementing a nursing professional practice model in a large
      health system.
AB  - A large healthcare system was challenged to develop a nursing professional
      practice model that would apply to and be understood by nurses at all levels and
      across all entities of the organization. A team was convened, composed of direct
      care nurses, educators, clinical nurse specialists, Magnet program directors,
      managers, and directors, representing 5 hospitals, the organization institute for
      nursing, and system support services. The group drafted a model describing
      nursing across the organization. The draft model was vetted in nursing governance
      councils across the entity. The model includes a theoretical framework; a
      mission, vision, and values; elements of professional practice; internal
      accountabilities; and nursing outcomes. Nurses learned about the model through
      Web-based and face-to-face training, through participation in a professional
      practice model blog and group discussions.

PMID- 22361876
TI  - Enhancing diversity in nursing: a partnership approach.
AB  - Recent census data highlight the ongoing shift toward greater levels of racial
      and ethnic diversity in the US population. In 2000, non-Hispanic whites accounted
      for 69% of the population. By 2010, this decreased to 64%. The Census Bureau
      predicts that minorities will become the majority over the upcoming decades. In
      nursing and other healthcare professions, however, a different picture emerges,
      with minorities consistently underrepresented. The authors describe the
      development, outcomes, and benefits of the clinical leadership collaborative for
      diversity in nursing. Strategies for overcoming barriers to increasing diversity
      in the nursing profession are addressed.

PMID- 22361877
TI  - The role of tropospheric ice surfaces in the elimination of the CFC substitute,
      trifluoroethanol.
AB  - This work provides uptake results of CF(3)CH(2)OH on ice over the temperature
      range 203-223 K using a coated wall flow tube coupled to mass spectrometric
      detection. For experiments over pure ice, the adsorption was fully reversible and
      the data could be described in terms of the Langmuir isotherm for the range of
      concentrations and temperatures studied. For this temperature range, DeltaH
      degrees (ads) = -46 +/- 16 kJ mol(-1) was obtained (error is 2sigma + 5%). For
      experiments on doped ice with nitric acid over the temperature range 203-223 K,
      the number of adsorbed molecules was slightly lower than over pure ice. At
      temperatures above 231 K, the extent of the reversible uptake of CF(3)CH(2)OH is
      enhanced in the presence of nitric acid due to coexistence of a liquid solution
      phase. Under such conditions the obtained solubility data follow Henry's law.
      Although pure ice and acid doped water surfaces do not permanently scavenge
      CF(3)CH(2)OH, the partitioning of CF(3)CH(2)OH between the gas phase and aqueous
      condensed phases may play a role as reservoirs or as a means of transport in the
      troposphere.

PMID- 22361878
TI  - Pityriasis versicolor atrophicans.

PMID- 22361879
TI  - Accurate reporting of adverse events in chronic lymphocytic leukemia and non
      Hodgkin lymphoma.
AB  - The treatment of lymphomas such as non-Hodgkin lymphoma (NHL) and chronic
      lymphocytic leukemia (CLL) has greatly advanced, especially over the last decade,
      with notable improvements in patient responses and survival times. However,
      adverse events remain an important, and often overlooked, issue in the management
      of these patients. Treatment of these malignancies is made additionally complex
      due to the occurrence of related severe cytopenias and other side effects. New
      agents to treat NHL and CLL are currently in clinical development; many of these
      are targeted agents with the added benefit of not producing the same adverse
      events (such as hematologic toxicity) observed with older cytotoxic
      chemotherapies. However, even these newer agents must be incorporated with
      caution into the clinical setting, as they have their own unique toxicity
      profiles and can even cause off-target effects when used at high doses. As these
      agents advance through clinical trials, clinicians must be able to recognize and
      manage associated adverse events. This monograph addresses these important
      points, with experts discussing adverse events due to the malignancies themselves
      as well as their associated treatments. Proper reporting of adverse events is
      critical, as are proper clinical trial design and long-term follow-up.

PMID- 22361880
TI  - The high-affinity choline transporter CHT1 is regulated by the ubiquitin ligase
      Nedd4-2.
AB  - The high-affinity choline transporter (CHT1), which is specifically expressed in
      cholinergic neurons, constitutes a rate-limiting step for acetylcholine
      synthesis. We have found that the exogenous ubiquitin ligase Nedd4-2 interacts
      with CHT1 expressed in HEK293 cells decreasing the amount of cell surface CHT1 by
      approximately 40%, and that small interfering RNA for endogenous Nedd4-2 enhances
      the choline uptake activity by CHT1 in HEK293 cells. These results indicate that
      Nedd4-2-mediated ubiquitination regulates the cell surface expression of CHT1 in
      cultured cells and suggest a possibility that treatments or drugs which inhibit
      the interaction between CHT1 and Nedd4-2 might be useful for diseases involving
      decrease in acetylcholine level such as Alzheimer's disease.

PMID- 22361881
TI  - Effects of a catechin-free fraction derived from green tea on gene expression of
      enzymes related to lipid metabolism in the mouse liver.
AB  - Many biological activities of green tea have been attributed to a major
      constituent, (minus;)-epigallocatechin gallate (EGCG). We previously reported
      that EGCG and an EGCG-free fraction derived from green tea modulated the gene
      expression of gluconeogenic enzymes, glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase, in the mouse liver. EGCG is also known to
      affect the gene expression of enzymes related to lipid metabolism. However, it
      remains to be examined whether or not a constituent other than EGCG contributes
      to the change in gene expression of these enzymes. In this study, we prepared an
      EGCG-free water-soluble fraction (GT-W), and examined its effects on the hepatic
      gene expression of lipogenic enzymes in mice. The results of quantitative real
      time PCR assays indicated that the dietary administration of GT-W for 4 weeks
      reduced the hepatic gene expression of lipogenic enzymes: fatty acid synthase,
      hydroxymethylglutaryl coenzyme A reductase, and acetyl-coenzyme A carboxylase
      alpha. Also, the gene expression of sterol regulatory element-binding
      transcription factor (Srebf)1 and/or Srebf2 was reduced, suggesting that the
      reduction of Srebfs contributed to the down-regulation of the lipogenic enzymes,
      since these transcription factors bind the promoter region to enhance their
      expression. The plasma levels of triglycerides and cholesterol were reduced with
      statistical significance in the group given a diet containing GT-W. These results
      suggest that in addition to EGCG, green tea contains some component(s) which may
      help to prevent arteriosclerosis and obesity.

PMID- 22361882
TI  - Geranylgeraniol oxidase activity involved in oxidative formation of
      geranylgeranoic acid in human hepatoma cells.
AB  - Geranylgeranoic acid (GGA), a 20-carbon acyclic polyprenoic acid (all-trans
      3,7,11,15-tetramethyl- 2,4,6,10,14-hexadecatetraenoic acid) and its derivatives
      were developed as synthetic "acyclic retinoids" for cancer chemoprevention.
      Previously, we have shown the natural occurrence of GGA in various medicinal
      herbs and reported enzymatic formation of GGA from geranylgeraniol (GGOH) through
      geranylgeranial (GGal) by rat liver homogenates. Here, we present several lines
      of evidence that a putative GGOH oxidase is involved in GGA synthesis by human
      hepatoma cell lysates. First, conversion of GGOH to GGal did not require
      exogenous NAD(+), whereas the conversion from GGal to GGA absolutely required
      additional NAD(+). Second, GGal synthesis from GGOH was coupled with consumption
      of oxygen from the reaction mixture. Third, GGOH-dependent GGal synthesis
      activity was proteinase K-resistant and even enhanced by proteinase K treatment;
      GGOH oxidase activity was enriched in the mitochondrial fraction. Finally,
      recombinant human monoamine oxidase (MAO)-B, but not MAO-A catalyzed oxidation of
      GGOH to GGal. These data suggest that a putative mitochondrial GGOH oxidase is
      involved in the initial step of GGA synthesis from GGOH.

PMID- 22361883
TI  - Screening of natural medicines that efficiently activate neurite outgrowth in
      PC12 cells in C2C12-cultured medium.
AB  - We have studied the effects of natural medicines on neurite outgrowth in PC12D
      cells in a cultured medium of C2C12 cells. Derived from mouse myoblasts, the
      C2C12 cells secrete neurotrophic factors including nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). The secretion
      of these neurotrophins from C2C12 cells stimulate neurite outgrowth in PC12D
      cells. We have screened a total of 120 samples and found five natural medicines:
      Trichosanthes Root, Asiasarum Root, Lycium Bark, Sinomenium Stem, and Dictamni
      radicis Cortex, that enhance the activity of C2C12-cultured medium to stimulate
      neurite outgrowth in PC12D cells. These natural medicines promoted not only
      neurite outgrowth but also stabilized the neurite formation in PC12D cells for
      several days. RT-PCR analysis showed that NGF was significantly increased with
      Trichosanthes and Lycium Bark. However, BDNF was slightly decreased with Lycium
      Bark, Sinomenium Stem, and Dictamni radicis Cortex. NT-3 was increased slightly
      by all of these natural medicines except Sinomenium Stem. All these five natural
      medicines significantly increased the number and length of neurites in PC12D
      cells in co-culture with C2C12 cells.

PMID- 22361884
TI  - The developmental plasticity of colocalization pattern of peptide YY and glucagon
      like peptide-1 in the endocrine cells of bovine rectum.
AB  - Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced in endocrine
      cells that show distal distribution in each of small and large intestine. They
      are colocalized in the same endocrine cells at different ratios depending on the
      animal species. The present study examined the possibility of plasticity in the
      colocalization pattern in the bovine rectum, which is known to contain endocrine
      cells at a high concentration. Consecutive sections from different pre- and
      postnatal stages were stained immunohistochemically. The immunoreactive (IR)
      cells were divided into three groups: 1) cells IR for both PYY and GLP-1 (PYY/GLP
      1-IR cells), 2) cells IR only for PYY (PYY-IR cells), and 3) cells IR only for
      GLP-1 (GLP-1-IR cells). The percentage of PYY/GLP-1-IR cells was high in the
      prenatal (early, mid- and late fetuses) and suckling stages, whereas it decreased
      in the herbivorous (weaning, weaned and adult) stages. In contrast, percentages
      of PYY and GLP-1-IR single cells were low in the prenatal and suckling stages and
      increased after the suckling stage. PYY/GLP-1 endocrine cells may adapt to the
      change of digestion depending on feeding habits and/or specific developmental
      stages of cattle. The present results suggest the developmental plasticity of the
      colocalization pattern of gut hormones with nutritional transition.

PMID- 22361885
TI  - Toll like receptor 5 ligand induces monocyte chemoattractant protein-1 in mouse
      osteoblastic cells.
AB  - Flagellin, the ligand of Toll like receptor 5, is the major subunit of bacterial
      flagella. Flagellin stimulates various cells to release chemokines. Monocyte
      chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family that is
      involved in monocyte infiltration in inflammatory diseases. It has been reported
      that serum MCP-1 levels increase proportionally with the severity of periodontal
      disease. Inflammatory mediators induce MCP-1 production in various cells,
      including osteoblasts. However, it remains unclear whether MCP-1 is released from
      osteoblasts in response to flagellin. In the present study, we investigated the
      effects of flagellin on the expression of MCP-1 in the mouse osteoblastic cell
      line, MC3T3-E1 (E1) cells. Flagellin markedly increased MCP-1 mRNA level in a
      dose-dependent manner. The effect of flagellin on MCP-1 mRNA expression in E1
      cells was transient, with a peak at 1 h. Concomitant with MCP-1 mRNA expression,
      MCP-1 protein levels were clearly elevated at 3 h after flagellin exposure. In
      addition, we revealed that JNK and MEK-ERK1/2 are involved in flagellin-induced
      MCP-1 expression in E1 cells. These results indicated that bacterial flagellin
      may play an important role in the progression of periodontitis. Results of
      further studies will provide more clues to the prevention of periodontal
      diseases.

PMID- 22361886
TI  - Different effects of two types of H2-receptor antagonists, famotidine and
      roxatidine, on the mucus barrier of rat gastric mucosa.
AB  - Compared with the aggressive factors, little attention has been paid to the
      mucosal defensive factors in ulcer therapy, and the role of the H2-receptor
      antagonists in gastric mucosal protection has not been well characterized. In the
      present study, the effects of different types of H2-receptor antagonists
      (famotidine and roxatidine) on rat gastric mucus cells were investigated using
      both biochemical and histological methods. Each drug (famotidine, 3 mg/kg;
      roxatidine, 100 mg/kg) was orally administered to rats by gavage once daily for 7
      days. The biosynthesis and tissue content of mucin were compared in the gastric
      mucosa treated with each drug. Using anti-mucin monoclonal antibodies, the mucin
      content and immunohistochemical localization were also compared. Both the
      biosynthesis and the accumulation of gastric mucin were significantly decreased
      in the famotidine-treated rats, but not in the roxatidine. Both the content and
      the immunoreactivity of surface mucus cell-derived mucin were reduced by
      famotidine, while they were maintained in roxatidine-treated rat stomachs. There
      was no difference between the groups in the content and immunoreactivity of
      mucous neck cell-derived mucin. H2-receptor antagonists should be classified in
      relation to gastric surface mucus cell function, raising the possibility of more
      effective ulcer therapy.

PMID- 22361888
TI  - Fragrant environment with alpha-pinene decreases tumor growth in mice.
AB  - Stress is believed to be harmful to not only mental but also physical health.
      However, proving a link between stress and disease is difficult. A recent study
      reported that an environmental enrichment reduced cancer growth via the
      hypothalamic-pituitary-adrenal axis and leptin. Here, we report that mice kept in
      a fragrant environment enriched with alpha-pinene show reduced melanoma growth.
      Tumor volume of mice under the alpha-pinene environment was about 40% smaller
      than that in the control mice. alpha-Pinene had no inhibitory effect on melanoma
      cell proliferation in vitro, suggesting that this effect was not a direct effect
      of alpha-pinene. These results suggest that the provision of a fragrant
      environment may be an important factor in the therapeutic approach to cancer.

PMID- 22361887
TI  - The 129 genetic background affects susceptibility to glomerulosclerosis in
      tensin2-deficient mice.
AB  - The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant
      proteinuria, podocyte morphological abnormalities and increased extracellular
      matrix accumulation in the glomeruli, which represent the final common pathology
      associated with a variety of kidney diseases leading to end-stage renal failure.
      Previously, we demonstrated that GS in ICGN mice can be attributed to the
      deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J
      (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular
      strain; however, its susceptibility to GS has not been defined. Thus, to
      determine whether 129/Sv is resistant or susceptible to GS, we produced a
      congenic strain carrying Tns2(nep) on the 129(+Ter)/Sv (129T) background. 129T
      congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia,
      increases in BUN, or any severe pathological changes until at least 16 weeks of
      age. These results indicate that 129T is resistant to GS. Although their usage in
      biomedical studies is already widespread, 129/Sv mice may afford a late-onset and
      unique strain applicable to kidney disease research.

PMID- 22361889
TI  - Difference in glucose intolerance between C57BL/6J and ICR strain mice with
      streptozotocin/nicotinamide-induced diabetes.
AB  - Blood glucose and plasma insulin levels between C57BL/6J and ICR strain mice with
      nicotinamide (NA) and streptozotocin (STZ)-induced diabetes were compared to
      establish a suitable strain of the experimental diabetic mouse model. The mice
      were intraperitoneally treated twice with STZ (100 mg/kg) 15 min after injection
      of NA (120 mg/kg) at a 1-day interval, and non-fasting blood glucose level was
      then weekly monitored for 5 weeks. The blood glucose level in ICR mice gradually
      increased and was about 2-times higher than that in C57BL/6J mice at the end of
      the observation. The plasma insulin level in ICR mice was comparatively low,
      compared with that in C57BL/6J mice. ICR mice were also markedly glucose
      intolerant when oral glucose tolerance test was performed. These results indicate
      that ICR strain is more sensitive than C57BL/6J strain as a mouse model with
      NA/STZ-induced mild diabetes.

PMID- 22361890
TI  - Rapid microarray processing using a disposable hybridization chamber with an
      integrated micropump.
AB  - We present a disposable microarray hybridization chamber with an integrated
      micropump to speed up diffusion based reaction kinetics by generating convective
      flow. The time-to-result for the hybridization reaction was reduced from 60 min
      (standard protocol) down to 15 min for a commercially available microarray. The
      integrated displacement micropump is pneumatically actuated. It includes two
      active microvalves and is designed for low-cost, high volume manufacturing. The
      setup is made out of two microstructured polymer parts realized in polycarbonate
      (PC) separated by a 25 MUm thermoplastic elastomer (TPE) membrane. Pump rate can
      be controlled between 0.3 MUl s(-1) and 5.7 MUl s(-1) at actuation frequencies
      between 0.2 Hz and 8.0 Hz, respectively.

PMID- 22361891
TI  - Organic nonvolatile memory devices with charge trapping multilayer graphene film.
AB  - We fabricated an array-type organic nonvolatile memory device with multilayer
      graphene (MLG) film embedded in polyimide (PI) layers. The memory devices showed
      a high ON/OFF ratio (over 10(6)) and a long retention time (over 10(4) s). The
      switching of the Al/PI/MLG/PI/Al memory devices was due to the presence of the
      MLG film inserted into the PI layers. The double-log current-voltage
      characteristics could be explained by the space-charge-limited current conduction
      based on a charge-trap model. A conductive atomic force microscopy found that the
      conduction paths in the low-resistance ON state were distributed in a highly
      localized area, which was associated with a carbon-rich filamentary switching
      mechanism.

PMID- 22361892
TI  - Intersibling variability of retinopathy of prematurity in twins and its risk
      factors.
AB  - To study intersibling variability of retinopathy of prematurity (ROP) in twins
      and determine its risk factors. A retrospective chart review of twin neonates
      developing ROP at a tertiary center over a 5 year period (January 2004 to
      December 2008). Twin pairs with intersibling variability of ROP were retrieved
      based on one of the following criterion: (1) two-stage difference in ROP between
      siblings, (2) one sibling with treatable ROP and the other with spontaneously
      regressed ROP, or (3) one sibling with aggressive posterior ROP and the other
      with staged ROP. Babies with greater severity of ROP were included in group A
      (case group) and their siblings with less severity in group B (control group).The
      two groups were compared for birth weight, birth order and putative post
      gestational risk factors. Thirty-five twin pairs developed ROP of which 28 pairs
      (80%) had severe intersibling variability. Twenty-one pairs with complete
      information about risk factors were analyzed. The birth weight of the case group
      was 1212.1 +/- 248.3 g (mean +/- SD) and control group 1172.1 +/- 216.5 g (mean
      +/- SD) (p = 0.33). In twelve of the 21 pairs the second born twin had more
      severe ROP. However, birth order was not a significant predictor (p = 0.664).
      Various post-gestational risk factors did not differ significantly between the
      two groups [oxygen administration (p = 1), sepsis (p = 0.625), exchange
      transfusion (p = 1), blood transfusion (p = 0.325), respiratory distress syndrome
      (p = 1), anemia (p = 0.125), apnea (0.375), neonatal jaundice (p = 1), patent
      ductus arteriosus (p = 0.5) and hypoglycemia (p = 1)]. The majority of the twins
      developing ROP had severe intersibling variability. Birth weight, birth order and
      post-gestational neonatal risk factor were not predictive of more severe ROP in a
      twin sibling.

PMID- 22361893
TI  - Survey of practice preference pattern in antibiotic prophylaxis against
      endophthalmitis after cataract surgery in Singapore.
AB  - To determine practice preference of prophylaxis against post-cataract surgery
      endophthalmitis in Singapore. Prospective nationwide survey of all registered
      ophthalmologists through telephone, e-mail or postal questionnaires. A response
      rate of 76.6% was obtained from 121 out of 158 eligible ophthalmologists.
      Awareness of the recommendations made by the European Society of Cataract and
      refractive surgeons (ESCRS) endophthalmitis study was noticed in 98 (81.0%)
      respondents. Out of the 121 respondents, 85 (70.2%) do not use intracameral
      antibiotic prophylaxis. Of the 36 respondents using intracameral antibiotics, 34
      (94.4%) used cefazolin. The reasons cited for not adopting intracameral
      antibiotic prophylaxis included financial costs, the relatively low risk of
      endophthalmitis after cataract surgery, the burden of dilution and the fear of
      toxic anterior segment syndrome. More than half (65, 53.7%) of respondents would
      use intracameral antibiotic prophylaxis if it were available commercially. The
      most commonly practiced prophylaxis (94, 77.7%) was preoperative topical
      antibiotics. The majority of ophthalmologists in Singapore have not adopted the
      use of intracameral antibiotics, with most preferring the use of pre- and
      postoperative prophylactic topical antibiotics, despite knowledge of the ESCRS
      endophthalmitis study.

PMID- 22361894
TI  - Comparing the long-term retention of a physiology course for medical students
      with the traditional and problem-based learning.
AB  - The rapid improvements in medical sciences and the ever-increasing related data,
      however, require novel methods of instruction. One such method, which has been
      given less than due attention in Iran, is problem-based learning (PBL). In this
      study, we aimed to evaluate the impact of study skills and the PBL methods on
      short and long-term retention of information provided for medical students in the
      course of respiratory physiology and compare it with traditional learning method.
      In this study, 39 medical students from Medical School of Kerman University of
      Medical Sciences, Kerman, Iran (2006-2010) were enrolled in the study and
      allocated randomly in three equal groups (13 in each group). All groups underwent
      a pre-test to be assessed for their basic information regarding respiratory
      physiology. Two groups were instructed using the traditional method, and one
      group used PBL. Among the two groups of the traditional method, one was
      instructed about study skills and the other was not. Once the PBL group took the
      study skill workshop, they were aided by tutors for their education. In the final
      term test, those students who had learned study skills and were instructed with
      the traditional method scored higher compared to other groups (p < 0.05).
      However, in the 1 year (p < 0.05) and 4 year (p < 0.01) interval examinations,
      the PBL group achieved significantly higher scores. Despite the fact that PBL had
      no positive effect on the final term exam of our students, it yielded a more
      profound and retained understanding of the subject course. Moreover, considering
      the positive effect of study skills on long-term student scores, we recommend
      students to receive instructions regarding the appropriate study skills when
      initiated into universities.

PMID- 22361895
TI  - Synthesis and biological profiling of tellimagrandin I and analogues reveals that
      the medium ring can significantly modulate biological activity.
AB  - A novel synthesis of the ellagitannin natural product tellimagrandin I and a
      series of medium ring analogues is described. These compounds were all
      subsequently screened for redox activity, ability to precipitate protein and
      cellular phenotype in HeLa cells. From this we have shown that all properties can
      be modulated independently by varying ring size and by moving the ester out of
      conjugation with the biaryl ring system. Increasing ring size increased redox
      activity and cytotoxicity, leading to the identification of a compound (10) which
      was significantly more cytotoxic. In addition compounds identified with a redox
      active scaffold and low cytotoxicity may be employed as a new class of redox
      probes.

PMID- 22361896
TI  - Laying out ground rules for protein-aided nanofabrication: ZnO synthesis at 70
      degrees C as a case study.
AB  - Designer proteins that incorporate solid-binding peptides hold promise to control
      the nucleation, growth, morphology, and assembly of inorganic phases under mild
      conditions of temperature and pressure. However, protein-aided nanofabrication
      remains more art than science and some materials can only be synthesized at
      temperatures that cause most mesophilic proteins to unfold. Using zinc oxide
      (ZnO) synthesis at 70 degrees C as case study, we show here that seemingly
      unimportant variables, such as the carry-over concentration of Tris buffer and
      the "empty" host protein scaffold can exert a significant influence on materials
      morphology. We also show that, once well-controlled conditions are established,
      thermodynamic predictions and adsorption isotherms are powerful tools to
      understand how various ZnO-binding sequence inserted within the thermostable
      framework of Escherichia coli thioredoxin A (TrxA) affect inorganic
      morphogenesis.

PMID- 22361897
TI  - Synthesis of a 4,8-dialkoxy-benzo[1,2-b:4,5-b']difuran unit and its application
      in photovoltaic polymer.
AB  - A new building block of benzo[1,2-b:4,5-b']difuran (BDF) was firstly designed and
      synthesized. The newly designed unit was applied for constructing a new
      photovoltaic low band gap polymer, PBDFDTBT, which exhibited promising power
      conversion efficiency of 5.0%.

PMID- 22361899
TI  - An empirical examination of the management of return of individual research
      results and incidental findings in genomic biobanks.
AB  - PURPOSE: The purpose of this study was to examine and document the management and
      return of individual research results and incidental findings to research
      participants among biobanks. METHODS: A comprehensive Internet search was
      completed to identify biobanks and collect available documents about biobanks and
      their procedures and policies regarding the return of results. The Internet
      search was supplemented by an e-mail request to gather further such documents. A
      total of 2,366 documents were collected for analysis from a sample of 85
      biobanks. RESULTS: The major finding of this empirical work is that the majority
      of the biobanks in the sample do not address the return of individual research
      results and incidental findings in their publicly available documents.
      CONCLUSION: The results suggest that there is a need for more discussion and
      guidance about the most appropriate ways for biobanks to consider the return of
      individual research results and incidental findings and generate policies and
      procedures that address this issue.

PMID- 22361900
TI  - Secondary researchers' duties to return incidental findings and individual
      research results: a partial-entrustment account.
AB  - Existing attempts to explain why secondary researchers might have any obligation
      to return findings to the contributors of genetic samples falter because of the
      lack of any direct interaction between the secondary researchers and the
      contributors. The partial-entrustment account of these obligations defended here
      circumvents this problem by explaining how a chain of special responsibilities
      can be forged even in the absence of any direct interaction.Genet Med
      2012:14(4):467-472.

PMID- 22361898
TI  - Return of individual research results from genome-wide association studies:
      experience of the Electronic Medical Records and Genomics (eMERGE) Network.
AB  - PURPOSE: Return of individual genetic results to research participants, including
      participants in archives and biorepositories, is receiving increased attention.
      However, few groups have deliberated on specific results or weighed deliberations
      against relevant local contextual factors. METHODS: The Electronic Medical
      Records and Genomics (eMERGE) Network, which includes five biorepositories
      conducting genome-wide association studies, convened a return of results
      oversight committee to identify potentially returnable results. Network-wide
      deliberations were then brought to local constituencies for final decision
      making. RESULTS: Defining results that should be considered for return required
      input from clinicians with relevant expertise and much deliberation. The return
      of results oversight committee identified two sex chromosomal anomalies,
      Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V
      Leiden, as findings that could warrant reporting. Views about returning findings
      of HFE gene mutations associated with hemochromatosis were mixed due to low
      penetrance. Review of electronic medical records suggested that most participants
      with detected abnormalities were unaware of these findings. Local considerations
      relevant to return varied and, to date, four sites have elected not to return
      findings (return was not possible at one site). CONCLUSION: The eMERGE experience
      reveals the complexity of return of results decision making and provides a
      potential deliberative model for adoption in other collaborative contexts.

PMID- 22361901
TI  - A closer look revisited: are we subjects or are we donors?
AB  - The author offers personal reflections on the implications of the article
      "Managing Incidental Findings & Research Results in Genomic Research Involving
      Biobanks & Archived Datasets" in terms of how the article addresses serious
      knowledge disparities and differing expectations between participants and
      researchers.Genet Med 2012:14(4):458-460.

PMID- 22361902
TI  - The hunter becomes the hunted: when cleptobiotic insects are captured by their
      target ants.
AB  - Here we show that trying to rob prey (cleptobiosis) from a highly specialized
      predatory ant species is risky. To capture prey, Allomerus decemarticulatus
      workers build gallery-shaped traps on the stems of their associated myrmecophyte,
      Hirtella physophora. We wondered whether the frequent presence of immobilized
      prey on the trap attracted flying cleptoparasites. Nine social wasp species nest
      in the H. physophora foliage; of the six species studied, only Angiopolybia
      pallens rob prey from Allomerus colonies. For those H. physophora not sheltering
      wasps, we noted cleptobiosis by stingless bees (Trigona), social wasps (A.
      pallens and five Agelaia species), assassin bugs (Reduviidae), and flies. A
      relationship between the size of the robbers and their rate of capture by
      ambushing Allomerus workers was established for social wasps; small wasps were
      easily captured, while the largest never were. Reduviids, which are slow to
      extract their rostrum from prey, were always captured, while Trigona and flies
      often escaped. The balance sheet for the ants was positive vis-a-vis the
      reduviids and four out of the six social wasp species. For the latter, wasps
      began by cutting up parts of the prey's abdomen and were captured (or abandoned
      the prey) before the entire abdomen was retrieved so that the total weight of the
      captured wasps exceeded that of the prey abdomens. For A. pallens, we show that
      the number of individuals captured during attempts at cleptobiosis increases with
      the size of the Allomerus' prey.

PMID- 22361903
TI  - Assessing trophic position from nitrogen isotope ratios: effective calibration
      against spatially varying baselines.
AB  - Nitrogen isotope signatures (delta(15)N) provide powerful measures of the trophic
      positions of individuals, populations and communities. Obtaining reliable
      consumer delta(15)N values depends upon controlling for spatial variation in
      plant delta(15)N values, which form the trophic 'baseline'. However, recent
      studies make differing assumptions about the scale over which plant delta(15)N
      values vary, and approaches to baseline control differ markedly. We examined
      spatial variation in the delta(15)N values of plants and ants sampled from eight
      150-m transects in both unlogged and logged rainforests. We then investigated
      whether ant delta(15)N values were related to variation in plant delta(15)N
      values following baseline correction of ant values at two spatial scales: (1)
      using 'local' means of plants collected from the same transect and (2) using
      'global' means of plants collected from all transects within each forest type.
      Plant delta(15)N baselines varied by the equivalent of one trophic level within
      each forest type. Correcting ant delta(15)N values using global plant means
      resulted in consumer values that were strongly positively related to the transect
      baseline, whereas local corrections yielded reliable estimates of consumer
      trophic positions that were largely independent of transect baselines. These
      results were consistent at the community level and when three trophically
      distinct ant subfamilies and eight abundant ant species were considered
      separately. Our results suggest that assuming baselines do not vary can produce
      misleading estimates of consumer trophic positions. We therefore emphasise the
      importance of clearly defining and applying baseline corrections at a scale that
      accounts for spatial variation in plant delta(15)N values.

PMID- 22361904
TI  - Feeding preference of the South American endemic anomuran Aegla platensis
      (Decapoda, Anomura, Aeglidae).
AB  - In order to determine the feeding preference of Aegla platensis in streams and
      the importance of microorganisms in its detritivore diet, we carried out two
      experiments designed to evaluate the food preferences of A. platensis (1) among
      leaves with different levels of microbial colonization and (2) among insect
      larvae (Chironomidae, Simuliidae, Hydropsychidae) and microbially conditioned
      leaves. A. platensis preferred animal over plant food items; when only leaves
      were offered, this aeglid preferred the leaves with higher levels of
      microorganism conditioning.

PMID- 22361905
TI  - Mn(II) and Zn(II) interactions with peptide fragments from Parkinson's disease
      genes.
AB  - Two peptide sequences from PARK9 Parkinson's disease gene, ProAspGluLysHisGluLeu,
      (P(1)D(2)E(3)K(4)H(5)E(6)L(7)) (1) and PheCysGlyAspGlyAlaAsnAspCysGly
      (F(1)C(2)G(3)D(4)G(5)A(6)N(7)D(8)C(9)G(10)) (2) were tested for Mn(II), Zn(II)
      and Ca(II) binding. The fragments are located from residues 1165 to 1171 and 1184
      to 1193 in the PARK9 encoded protein. This protein can protect cells from
      poisoning of manganese, which is an environmental risk factor for a Parkinson's
      disease-like syndrome. Mono- and bi-dimensional NMR spectroscopy has been used to
      understand the details of metal binding sites at different pH values and at
      different ligand to metal molar ratios. Mn(II) and Zn(II) coordination with
      peptide (1) involves imidazole N(epsilon) or N(delta) of His(5) and carboxyl
      gamma-O of Asp(2), Glu(3) and Glu(6) residues. Six donor atoms participate in
      Mn(II) binding resulting in a distorted octahedral geometry, possibly involving
      bidentate interaction of carboxyl groups; four donor atoms participate in Zn(II)
      binding resulting in a tetracoordinate geometry. Mn(II) and Zn(II) coordination
      involves the two cysteine residues with peptide (2); Mn(II) accepts additional
      ligand bonds from the carboxyl gamma-O of Asp(4) and Asp(8) to complete the
      coordination sphere; the unoccupied sites may contain solvent molecules. The
      failure of Ca(II) ions to bind to either peptide (1) or (2) appears to result,
      under our conditions, from the absence of chelating properties in the chosen
      fragments.

PMID- 22361908
TI  - Incidence and neurological outcomes of aneurysm rupture during interventional
      neuroradiology procedures in a hybrid operating suite.
AB  - A hybrid operating suite, where craniotomy, brain CT scanning, fluoroscopy, and
      angiography can be performed on the same operating table, is becoming popular
      among neurosurgeons. However, whether use of a hybrid operating suite can improve
      neurological outcome has not been studied. We reviewed the incidence and outcomes
      of ruptures of cerebral vascular lesions during interventional neuroradiology
      procedures performed in our hybrid operating suite. Of 602 patients who underwent
      coil embolization under general anesthesia, five cases of intraprocedural rupture
      of the aneurysms were identified. Despite emergency neurosurgical intervention
      within 2 h of rupture of the aneurysms, two of these five patients died and one
      patient had permanent neurological deficit postsurgery. Whether use of a hybrid
      operating suite improves neurological outcome remains uncertain.

PMID- 22361909
TI  - Ultrasound-guided central venous catheterization: efficacy of simultaneous
      perioperative ultrasonographic scanning for the presence of carotid plaques in
      the prevention of the perioperative development of ischemic stroke.

PMID- 22361910
TI  - Performance of WHO growth standards on Indian children with growth related
      disorders.
AB  - OBJECTIVE: To assess performance of WHO 2006 standards on anthropometric
      measurements of children referred for growth related disorders to a speciality
      pediatric clinic in Pune, India, from June 2006 through June 2010. METHODS: Data
      presented in this study were collected retrospectively from case records of all
      children from birth to 60 mo (n=1840, mean age 2.7+/-1.3 y) who presented with
      growth related disorders; healthy age and sex matched children were recruited as
      controls (n=824, mean age 2.8+/-1.2 y). Children were divided as per their
      clinical diagnosis into eight different groups: growth hormone deficiency, bone
      disorders, syndromic short stature, familial short stature, hypothyroidism,
      nutritional and systemic disorder, other endocrinopathies and overgrowth
      disorders. Anthropometric parameters for all study subjects were converted to
      standard deviation scores (SD scores) using the WHO Anthro 2005. RESULTS: Mean
      height SD scores of children with growth related disorders were significantly
      lower than that of the controls, while that of the tall children were
      significantly higher (p<0.05). All children who were clinically very short were
      below the 1st percentile, while none of the children with overgrowth or normal
      children were classified as stunted. Weight for height SD scores of children with
      nutritional and systemic disorders were the lowest, while those for the obese
      children were the highest. CONCLUSIONS: The present results suggest that the WHO
      2006 growth standards classify children with growth disorders appropriately and
      the classification is in concordance with the clinical assessment. They provide
      health practitioners in a clinical setting with an effective tool to assess
      growth of children.

PMID- 22361911
TI  - The significance of enterohepatic circulation in the causation neonatal
      hyperbilirubinemia.

PMID- 22361913
TI  - Tautomerization in the formation and collision-induced dissociation of alkali
      metal cation-cytosine complexes.
AB  - Noncovalent interactions between alkali metal cations and the various low-energy
      tautomeric forms of cytosine are investigated both experimentally and
      theoretically. Threshold collision-induced dissociation (CID) of M(+)(cytosine)
      complexes with Xe is studied using guided ion beam tandem mass spectrometry,
      where M(+) = Li(+), Na(+), and K(+). In all cases, the only dissociation pathway
      observed corresponds to endothermic loss of the intact cytosine molecule. The
      cross-section thresholds are interpreted to yield 0 and 298 K bond dissociation
      energies (BDEs) for the M(+)(cytosine) complexes after accounting for the effects
      of multiple ion-neutral collisions, the kinetic and internal energy distributions
      of the reactants, and dissociation lifetimes. Ab initio calculations are
      performed at the MP2(full)/6-31G* level of theory to determine the structures of
      the neutral cytosine tautomers, the M(+)(cytosine) complexes, and the TSs for
      unimolecular tautomerization. The molecular parameters derived from these
      structures are employed for the calculation of the unimolecular rates for
      tautomerization and the thermochemical analysis of the experimental data.
      Theoretical BDEs of the various M(+)(cytosine) complexes and the energy barriers
      for the unimolecular tautomerization of these complexes are determined at
      MP2(full)/6-311+G(2d,2p) level of theory using the MP2(full)/6-31G* optimized
      geometries. In addition, BDEs for the Li(+)(cytosine) complexes are also
      determined at the G3 level of theory. Based upon the tautomeric mixture generated
      upon thermal vaporization of cytosine, calculated M(+)-cytosine BDEs and barriers
      to tautomerization for the low-energy tautomeric forms of M(+)(cytosine), and
      measured thresholds for CID of M(+)(cytosine) complexes, we conclude that
      tautomerization occurs during both complex formation and CID.

PMID- 22361914
TI  - Loss of genomic DNA copy numbers in the p18, p16, p27 and RB loci in blastic
      plasmacytoid dendritic cell neoplasm.

PMID- 22361912
TI  - Prosthetic joint infections: radionuclide state-of-the-art imaging.
AB  - Prosthetic joint replacement surgery is performed with increasing frequency.
      Overall the incidence of prosthetic joint infection (PJI) and subsequently
      prosthesis revision failure is estimated to be between 1 and 3%. Differentiating
      infection from aseptic mechanical loosening, which is the most common cause of
      prosthetic failure, is especially important because of different types of
      therapeutic management. Despite a thorough patient history, physical examination,
      multiple diagnostic tests and complex algorithms, differentiating PJI from
      aseptic loosening remains challenging. Among imaging modalities, radiographs are
      neither sensitive nor specific and cross-sectional imaging techniques, such as
      computed tomography and magnetic resonance imaging, are limited by hardware
      induced artefacts. Radionuclide imaging reflects functional rather than
      anatomical changes and is not hampered by the presence of a metallic joint
      prosthesis. As a result scintigraphy is currently the modality of choice in the
      investigation of suspected PJI. Unfortunately, there is no true consensus about
      the gold standard technique since there are several drawbacks and limitations
      inherent to each modality. Bone scintigraphy (BS) is sensitive for identifying
      the failed joint replacement, but cannot differentiate between infection and
      aseptic loosening. Combined bone/gallium scintigraphy (BS/GS) offers modest
      improvement over BS alone for diagnosing PJI. However, due to a number of
      drawbacks, BS/GS has generally been superseded by other techniques but it still
      may have a role in neutropenic patients. Radiolabelled leucocyte scintigraphy
      remains the gold standard technique for diagnosing neutrophil-mediated processes.
      It seems to be that combined in vitro labelled leucocyte/bone marrow scintigraphy
      (LS/BMS), with an accuracy of about 90%, is currently the imaging modality of
      choice for diagnosing PJI. There are, however, significant limitations using in
      vitro labelled leucocytes and considerable effort has been devoted to developing
      alternative radiotracers, such as radiolabelled HIGs, liposomes, antigranulocyte
      antibodies and fragments, as well as more investigational tracers such as
      radiolabelled antibiotics, antimicrobial peptides, bacteriophages and thymidine
      kinase. On the other hand, positron emission tomography (PET) is still growing in
      the field of PJI imaging with radiotracers such as (18)F-fluorodeoxyglucose
      (FDG), (18)F-FDG white blood cells and (18)F-fluoride. But unfortunately this
      superb tomographic technique will only receive full acceptance when specific PET
      uptake patterns can be successfully developed. The emergence of hybrid modality
      imaging using integrated single photon emission computed tomography (SPECT) and
      PET with computed tomography (SPECT/CT and PET/CT) may also have a contributing
      role for more accurate assessment of joint replacement complications, especially
      combined with new radiotracers such as (68)Ga and (64)Cu. Finally, in searching
      for infection-specific tracers, currently there is no such diagnostic agent
      available.

PMID- 22361915
TI  - Current treatment of peripheral T-cell lymphoma.
AB  - Peripheral T-cell lymphoma (PTCL) constitutes a rare and biologically diverse
      group of non-Hodgkin lymphomas (NHLs) that arise from clonal proliferation of
      mature T cells and natural killer cells. PTCLs are aggressive lymphomas with
      unfavorable prognoses. Outcome varies by subtype, but long-term survival is only
      about 10-30% for most types. The rarity of the PTCL disorders, together with a
      lack of randomized trials, means that current treatment regimens are based on
      those used for B-cell NHLs, typically including combination, anthracycline-based
      chemotherapy. However, most PTCLs exhibit low rates of response to these
      regimens, as well as infrequent durable remissions. In recent years, advances in
      diagnostic methodologies have improved understanding of PTCL pathobiology and
      have resulted in better characterization of the different subtypes of PTCL. It is
      now acknowledged that these disorders behave differently than the B-cell NHLs and
      that each subtype warrants a distinct treatment approach. Development of PTCL
      specific treatments has gained momentum, with much research focused on
      investigating ways to intensify the chemotherapy regimen, such as adding new
      drugs to frontline chemotherapy and consolidating first remissions with high-dose
      therapy and autologous stem cell transplant.

PMID- 22361916
TI  - Effects of pitavastatin on pressure overload-induced heart failure in mice.
AB  - BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins),
      which are widely used to lower plasma cholesterol levels, have been reported to
      have various pleiotropic effects such as protective effect of endothelial cells,
      angiogenic effect, antioxidant effect and anti-inflammatory effect. It is
      unclear, however, whether statins have any effects on the progression from left
      ventricular (LV) hypertrophy to heart failure in the established hypertrophied
      heart. METHODS AND RESULTS: C57BL/6 mice were treated with pitavastatin (pitava)
      or vehicle (control) from 2 weeks (established hypertrophy stage) after
      transverse aortic constriction (TAC) and the treatment was continued for 4 weeks.
      Pitavastatin significantly inhibited the progression from LV hypertrophy to heart
      failure as assessed on echocardiography. The cardiomyocyte cross-sectional area
      was significantly increased in the control group compared to the sham-operated
      mice (sham group), but it was not significantly different between the control
      group and the pitava group at 6 weeks after TAC. Moreover, pitavastatin induced
      myocardial angiogenesis (ratio of number of endothelial cells to cardiomyocytes)
      and decreased the myocardial fibrosis and oxidative stress. The expression of
      angiopoietin-1 in the heart was significantly increased by pitavastatin at 6
      weeks after TAC. CONCLUSIONS: Pitavastatin has preventive effects on the
      progression of heart failure even in the hypertrophied heart.

PMID- 22361917
TI  - Novel device that produces carbon dioxide mist for myocardial infarction
      treatment in rats.
AB  - BACKGROUND: Carbon dioxide (CO(2)) baths have been used to treat a variety of
      diseases, but developing an artificial bath of highly concentrated CO(2) is
      difficult. Here, we tried the efficacy of a novel device instead of a CO(2) bath.
      METHODS AND RESULTS: Using a device equipped with double fluid nozzles, CO(2) gas
      and H(2)O were compounded and compressed at 4 barometric pressures. As a result,
      CO(2) gas was dissolved in H(2)O, which contained a few micrometers of CO(2)
      particles, namely, a CO(2) mist. Wistar rats with myocardial infarction (MI) by
      ligation of the left coronary artery were percutaneously administered CO(2) mist
      or CO(2) gas alone or no treatment for 30 min daily. With regard to tissue blood
      flow during treatment, the group treated with CO(2) mist had significantly
      increased tissue oxygenated hemoglobin levels and tissue saturation levels, and
      significantly decreased deoxygenated hemoglobin levels compared with the group
      treated with CO(2) gas. After 4 weeks treatment, the group treated with CO(2)
      mist had a significantly improved ejection fraction by echocardiography compared
      with the untreated group. Interestingly, the group treated with CO(2) mist had
      significantly increased nitrate concentrations in serum and vascular endothelial
      growth factor mRNA expression levels in the myocardium compared with the
      untreated group. CONCLUSIONS: Our new mist production device may be potentially
      useful for the treatment of heart failure caused by MI.

PMID- 22361919
TI  - Intravenous infusion of ultra-short-acting beta-blocker for postoperative atrial
      fibrillation is the one of choice.

PMID- 22361918
TI  - Landiolol, an ultra-short-acting beta1-blocker, more effectively terminates
      atrial fibrillation than diltiazem after open heart surgery: prospective,
      multicenter, randomized, open-label study (JL-KNIGHT study).
AB  - BACKGROUND: Recent studies have suggested that esmolol is the first choice for
      rate control in patients with postoperative atrial fibrillation (AF) after
      coronary artery bypass surgery, but side-effects of esmolol such as hypotension
      are problematic. To overcome this problem, landiolol, an ultra-short-acting
      beta(1)-blocker with a less negative inotropic effect than esmolol, has been
      developed. The aim of the present study was to investigate whether landiolol was
      effective for both rate control and conversion to normal sinus rhythm (NSR).
      METHODS AND RESULTS: A prospective, randomized, open-label comparison between
      i.v. landiolol and diltiazem in patients with postoperative AF was undertaken
      between January 2008 and June 2009 in Japan. Of 335 patients included in the
      analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR
      within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the
      landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P<0.05).
      The incidence of hypotension was lower in the landiolol group (4/35, 11.4%)
      compared with the diltiazem group (11/36, 30.6%; P<0.05). The incidence of
      bradycardia was also lower in the landiolol group (0%) compared with the
      diltiazem group (4/36, 11.1%; P<0.05). CONCLUSIONS: Landiolol is more effective
      and safer than diltiazem for patients with postoperative AF after open heart
      surgery.

PMID- 22361920
TI  - Normal values of real-time 3-dimensional echocardiographic parameters in a
      healthy Japanese population: the JAMP-3D Study.
AB  - BACKGROUND: The recently developed real-time 3-dimensional echocardiography
      (RT3DE) is a promising imaging method to quantify cardiac chamber volumes and
      their functions in clinical practice. However, normal reference values of RT3DE
      parameters have not been fully investigated in a large, healthy Japanese
      population. METHODS AND RESULTS: This study consisted of 410 healthy subjects
      aged from 20 to 69 years who had a RT3DE at one of the 23 collaborating
      institutions. All subjects had no history of cardiac disease and no risk factors.
      The mean values in men and women were as follows: 50 +/- 12 ml/m(2) and 46 +/- 9
      ml/m(2) for left ventricular (LV) end-diastolic volume index, 19 +/- 5 ml/m(2)
      and 17 +/- 4 ml/m(2) for end-systolic volume index, 61 +/- 4% and 63 +/- 4% for
      ejection fraction, 64 +/- 1 2 g/m(2) and 56 +/- 11 g/m(2) for mass index, 23 +/-
      6 ml/m(2) and 24 +/- 6 ml/m(2) for left atrial (LA) maximum volume index, 10 +/-
      3 ml/m(2) and 10 +/- 3 ml/m(2) for minimum volume index, and 58 +/- 6% and 58 +/-
      6% for percent volume change. LV sizes decreased with age, whereas LV mass index
      did not change. LA sizes slightly increased with age. CONCLUSIONS: This
      multicenter investigation determined normal reference values for LV and LA sizes,
      and their functional parameters on RT3DE in a large, healthy Japanese population.
      The results of the present study support the use of RT3DE for the diagnosis and
      management of cardiovascular disease.

PMID- 22361921
TI  - Hypoxic preconditioning--a cutting "aged" remedy for impaired angiogenesis.

PMID- 22361922
TI  - Wafer scale interdigitated nanoelectrode devices functionalized using a MEMS
      based deposition system.
AB  - This paper reports on a methodology to elaborate interdigitated nanoelectrode
      devices (INDs) at the wafer scale, relying on a mix-and-match process which
      combines proximity optical lithography and electron beam lithography. An optimum
      exposure dose allowed fabricating nanodevices, at the wafer level, with a
      successful yield of 97%. The final devices are bonded onto conventional TO-8
      packages. Electrical characterization in a short-circuited nanoelectrode is
      performed, revealing a 230 uOmega cm resistivity value at 23  degrees C. A MEMS
      based spotter made of cantilevers (called Bioplume) has been used to obtain
      precise functionalization of the INDs with sub-picoliter volume solutions. These
      INDs are the basis of multiple tunnel junction nanodevices, intended to serve as
      novel highly sensitive nanobiosensors.

PMID- 22361923
TI  - Comparison of children with autism spectrum disorder with and without
      schizophrenia spectrum traits: gender, season of birth, and mental health risk
      factors.
AB  - Children with autism spectrum disorder (ASD) with and without co-occurring
      schizophrenia spectrum traits (SST) were examined for differences in co-occurring
      psychiatric symptoms, background characteristics, and mental health risk factors.
      Participating mothers and teachers completed a DSM-IV-referenced rating scale and
      a background questionnaire (mothers only) describing 147 children (6-12 years)
      with ASD. There was a clear pattern of group differences in co-occurring
      psychiatric symptom severity (+SST > SST-) and background characteristics.
      Children with impairing SST had more mental health risk factors. Girls were more
      likely to be classified SST according to mothers' ratings. Children born in
      spring-summer were more likely to be classified non-SST by teachers' ratings.
      Findings provide tentative evidence that SST may be a useful marker of behavioral
      heterogeneity within the ASD clinical phenotype.

PMID- 22361924
TI  - Self-reported autism symptoms in adults with autism spectrum disorders.
AB  - Scores on the autism spectrum quotient (AQ) were examined in 65 adults with ASD.
      Maternal reports of symptoms were collected simultaneously using the autism
      diagnostic interview-revised (ADI-R) and the Vineland Screener. A slightly
      revised AQ administration procedure was used to accommodate adults with below
      average IQ. AQ scores were lower than in the original validation study, with only
      11 adults (17%) scoring above the proposed diagnostic cut-off and 24 (27%)
      exceeding the screening cut-off. Adults with higher IQs endorsed more symptoms
      than those with below average intelligence, but even when analyses were
      restricted to the 39 adults with at least average IQ, only 44% met the screening
      cut-off. AQ scores were not significantly correlated with ADI-R or Vineland
      scores.

PMID- 22361925
TI  - Correlates of bisexual behaviors among men who have sex with men in El Salvador.
AB  - Bisexual behaviors may increase transmission pathways of HIV and sexually
      transmitted infections (STIs) from a higher prevalence group to lower prevalence
      groups in El Salvador. In 2008, men who have sex with men (MSM) were recruited in
      San Salvador and San Miguel using respondent driven sampling. Participants were
      interviewed and tested for HIV and STIs. Sixteen seeds and 797 MSM participated;
      34.9% in San Salvador and 58.8% in San Miguel reported bisexual behavior.
      Bisexual behavior was associated with drug use (adjusted odds ratio (AOR) = 2.57,
      95% CI: 1.30-5.06) and insertive anal sex (AOR = 5.45, 95% CI: 3.01-9.87), and
      inversely associated with having a stable male partner (AOR = 0.47, 95% CI: 0.26
      0.84) and disclosing MSM behavior to family (AOR = 0.41, 95% CI: 0.22-0.75).
      Bisexual behavior was associated with risk behaviors with male and female
      partners that may be associated with HIV and STI transmission. Bisexual men
      displayed a distinct identity calling for tailored interventions.

PMID- 22361926
TI  - Click synthesized dianthryl-TTFV: an efficient fluorescent turn-on probe for
      transition metal ions.
AB  - Tetrathiafulvalene vinylogue (TTFV) was functionalized with two anthryl
      fluorophores via Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition, forming a
      dianthryl-TTFV hybrid to show fluorescent turn-on sensing behaviour for Cu(2+),
      Fe(2+), and Cd(2+) ions in THF with remarkably low detection limit down to the
      sub-ppm level.

PMID- 22361927
TI  - Tuberculosis in childhood.
AB  - There has been a recent global resurgence of tuberculosis (TB) fuelled by HIV
      infection and migration. Childhood TB represents a sentinel event in the
      community, suggesting recent transmission from an infectious adult. The diagnosis
      of TB in children is based on chest X-ray, tuberculin skin testing and
      mycobacterial staining/culture, although the diagnostic yield from these
      investigations is often lower than in adults. Newer diagnostic tests are being
      developed and may improve the diagnostic yield in childhood TB. Treatment of TB
      in children is similar to adults in that short-course multidrug treatment has
      been adopted as standard therapy in many national TB programmes. Compliance is a
      major determinant of the success of drug treatment and directly observed therapy
      has been adopted as a key component of TB treatment programmes. Although uncommon
      in children, multidrug-resistant TB is also increasing and treatment often
      involves longer courses of therapy with second-line drugs.

PMID- 22361928
TI  - N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary
      disease.
AB  - To develop an efficient therapy for chronic obstructive pulmonary disease (COPD),
      N-acetylcysteine (NAC) has been tested as a medication that can suppress various
      pathogenic processes in this disease. NAC is a thiol compound, which provides
      sulfhydryl groups. NAC can act as a precursor of reduced glutathione and as a
      direct reactive oxygen species scavenger, hence regulating the redox status in
      the cells. In this way NAC can interfere with several signaling pathways that
      play a role in regulating apoptosis, angiogenesis, cell growth and inflammatory
      response. Mucus hypersecretion has been reported in COPD and in other respiratory
      conditions. Two pathological processes have been described to play an important
      role in COPD, namely oxidative stress and inflammation. Both of these processes
      can induce mucin gene expression leading to mucin production. NAC, therefore, may
      influence mucin expression by acting on oxidative stress and inflammation, and
      play a role as a mucolytic agent. In this review we focus on the mucolysis of NAC
      in the management of COPD.

PMID- 22361929
TI  - Establishment and characterization of six human gastric carcinoma cell lines,
      including one naturally infected with Epstein-Barr virus.
AB  - We report the characterization of six new gastric carcinoma cell lines
      (designated NCC-19, NCC-20, NCC-24, NCC-59, SNU-1750 and SNU-1967) established
      from primary tumor samples of Korean patients. Four cell lines grew as adherent
      monolayers, one as both adherent and floating cell clumps and one as floating
      cell aggregates. The cell phenotypes, including the histopathology of the primary
      tumors and in vitro growth characteristics, were determined. We also performed
      molecular characterization, including DNA fingerprinting analysis and
      abnormalities of K-ras, p53, beta-catenin, and TGF-betaRII genes by PCR-SSCP and
      sequencing analyses. Population doubling times varied from 47-135 h. All cell
      lines showed relatively high viability, absence of mycoplasma or bacteria
      contamination and genetic heterogeneity by DNA fingerprinting analysis. Three
      lines had p53 mutations; one line had mutations in codon 13 (Gly13Asp) in K-ras
      and no line had a beta-catenin mutation. NCC-59 cell line had a -1-bp mutation in
      10-bp poly deoxy adenine repeat tract of the TGF-betaRII gene. Moreover, NCC-24
      gastric cancer cell line was found to be infected with Epstein-Barr virus (EBV).
      EBV infection was also shown in the original carcinoma tissue of the NCC-24 cell
      line. These well-characterized six gastric cancer cell lines should serve as
      useful tools for investigating the biological characteristics of gastric cancer
      and, in particular, NCC-24 may serve as a valuable model system to clarify the
      precise role of EBV in gastric carcinogenesis.

PMID- 22361930
TI  - Abstracts of the International Society for Cellular Oncology 2012 Conference,
      Joint Meeting with the European Workshop on Cytogenetics, and Molecular Genetics
      of Solid Tumors. March 4-8, 2012. Palma, Mallorca.

PMID- 22361931
TI  - A parallel diffusion-based microfluidic device for bacterial chemotaxis analysis.
AB  - We developed a multiple-channel microfluidic device for bacterial chemotaxis
      detection. Some characteristics such as easy operation, parallel sample adding
      design and fast result readout make this device convenient for most biology labs.
      The characteristic feature of the design is the agarose gel channels, which serve
      as a semi-permeable membrane. They can stop the fluid flow and prevent bacteria
      getting across, but permit the diffusion of small molecules. In the device
      fabrication process a novel thermal-based method was used to control the shape of
      agarose gel in the microfluidic channel. The chemical gradient is established by
      diffusion which can be precisely controlled and measured. Combined with an 8
      channel pipette, different attractants, repellent chemicals or different bacteria
      were analyzed by a two step operation with a readout time of one hour. This
      device may be useful in the high throughput detection of chemotaxis related
      molecules and genes.

PMID- 22361932
TI  - Team improvement and patient safety conferences: culture change and slowing the
      revolving door between skilled nursing facility and the hospital.
AB  - To improve the safety culture of a skilled nursing facility, we conducted
      multidisciplinary "Team Improvement for Patient and Safety" (TIPS) case
      conferences biweekly to identify causes of transfers to acute care hospitals and
      improvement opportunities. Staff perceptions of organizational patient safety
      culture were assessed with the Nursing Home Survey on Patient Safety Culture.
      Over the course of the year, we held 22 TIPS conferences. Mean item scores
      increased during the study, indicating improved staff perceptions of patient
      safety culture (P < .005).

PMID- 22361933
TI  - Self-assembly at room temperature of thermally stable discrete and extended
      oligomers of polycyclic aromatics on Ag(100): induced dipoles and cooperative
      effects.
AB  - Thermally stable nanoarchitectures are realized on the Ag(100) surface by self
      assembly of asymmetrically substituted arenes. The process is instigated by
      adsorption-induced molecule -> surface charge transfer that gives rise to in
      plane dipole moments. Observation and calculation indicate that cooperative
      interactions further enhance the stability of these polarizable systems.

PMID- 22361934
TI  - How to interpret epicardial adipose tissue as a cause of coronary artery disease:
      a meta-analysis.
AB  - BACKGROUND: Experimental and clinical studies have suggested that epicardial
      adipose tissue (EAT) may cause coronary artery disease (CAD). A meta-analysis was
      conducted to investigate the relationship between EAT and CAD. METHODS: A
      systematic literature search of Cochrane, Medline, Pubmed, Elsevier,
      Springerlink, Ovid, and Embase from their respective inceptions to August 2011
      was conducted using specific search terms such as 'epicardial adipose tissue' and
      'epicardial fat'. Data were extracted from applicable articles and mean
      differences or risk ratio, including 95% confidence intervals (CI), were
      calculated using RevMan 5.1 software. RESULTS: A total of 15 case-control studies
      and one case-sectional study (N=2872 patients) were identified. Compared with the
      non-CAD group, EAT thickness and volume were significantly higher in the CAD
      group (mean difference 1.57 mm, 95% CI: 0.74, 2.40, P<0.00001; mean difference
      15.22 ml, 95% CI: 7.58, 22.87, P<0.0001). Patients in the higher EAT tertile (>=
      100 ml) were more likely to have CAD compared with those in the lower EAT tertile
      (<100 ml) (risk ratio 0.69, 95% CI: 0.52, 0.92, P=0.01). Patients with coronary
      plaque also had increased EAT volume compared with patients without coronary
      plaque (mean difference 24.90 ml, 95% CI: 9.99, 39.81 P=0.001). EAT volume was
      not different in patients whose coronary artery calcium scores were less than or
      equal to 10 or greater than 10 (mean difference -17.28 ml, 95% CI: -52.01, 17.44,
      P=0.33). CONCLUSION: On the basis of the current evidence, EAT seems to be an
      effective marker in the prediction of CAD.

PMID- 22361935
TI  - Peptide receptor radionuclide therapy of Merkel cell carcinoma using
      (177)lutetium-labeled somatostatin analogs in combination with radiosensitizing
      chemotherapy: a potential novel treatment based on molecular pathology.
AB  - Few studies have been published on the safety and feasibility of synchronous use
      of peptide receptor radionuclide therapy (PRRNT), as source of internal radiation
      therapy, in combination with chemotherapy. In this study we reported a 53-year
      old man with stage IV Merkel cell carcinoma (MCC), who underwent synchronous
      internal radiation therapy and chemotherapy. Based on presumable poor prognosis
      with chemotherapy only, functional similarities of MCC with other neuroendocrine
      tumors and available evidence of effectiveness and safety of synchronous use of
      external beam radiation therapy and chemotherapy in treatment of high-risk MCC
      patients, our interdisciplinary neuroendocrine tumor board recommended him to add
      PRRNT to his ongoing chemotherapy. He received 2 courses of (177)Lu-DOTATATE(1,
      4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-D-Phe1-Tyr3-Thr8
      octreotide) in combination with ongoing 8 cycles of liposomal doxorubicin based
      on standard protocols. Response to therapy was evaluated by (18)F-FDG and
      (68)gallium-somatostatin-receptor PET/CT. There was an impressive improvement of
      the clinical symptoms. However, follow-up PET/CT studies showed mixed pattern of
      response. Synchronous use of PRRNT and radiosensitizing chemotherapy seems safe
      and feasible in high risk MCC patients, however, further prospective studies and
      clinical trials are warranted to provide reliable evidence of possible pitfalls
      and effectiveness of PRRNT and (68)Ga-somatostatin-receptor PET/CT in the
      management of MCC.

PMID- 22361936
TI  - Nucleic acid detection immunoassay for prostate-specific antigen based on immuno
      PCR methodology.
AB  - BACKGROUND: Serum prostate-specific antigen (PSA) concentrations after radical
      prostatectomy typically become undetectable with the use of current immunometric
      assay methods. Despite modern surgical techniques, 15%-30% of prostate cancer
      patients undergoing radical prostatectomy develop a biochemical recurrence during
      follow-up. Unfortunately, poor analytical sensitivity of standard PSA assays
      delays biochemical recurrence detection, and because of day-to-day assay
      imprecision ultrasensitive PSA assays cannot assess PSA kinetics. We developed an
      immuno-PCR assay for total PSA that has a limit of quantification >10 times lower
      than current ultrasensitive assays. METHODS: The 2-site immunometric assay for
      total PSA employed 2 monoclonal antibodies, one conjugated to a double-stranded
      DNA label and the other bound to paramagnetic microparticles. After several
      washing steps, quantification cycles were determined and values were converted to
      PSA concentrations. We characterized analytical performance and compared accuracy
      with a commercially available total PSA assay. RESULTS: The limit of
      quantification was 0.65 ng/L and the assay was linear in the range of 0.25-152.0
      ng/L. Total imprecision estimates at PSA concentrations of 3.8, 24.1, and 69.1
      ng/L were <15.2%, <9.4%, and <10.6%, respectively. Recovery of supplemented PSA
      ranged from 87.5% to 119.2% (mean 100.3%). Dilution recovery ranged from 96.4% to
      115.3% (mean 102.3%). There was no high-dose hook effect up to 50 000 ng/L of
      PSA. Comparison with the commercial PSA assay showed a regression slope of 1.06
      and a correlation coefficient of 0.996. CONCLUSIONS: The analytical
      characteristics of the assay support the use of this assay for the accurate and
      precise measurement of serum PSA, even at sub-nanogram-per-liter concentrations.

PMID- 22361937
TI  - Quantifying the effects of renal impairment on plasma concentrations of the
      neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine-
      and amphetamine-regulated transcript.

PMID- 22361938
TI  - Genetic susceptibility for coronary heart disease and type 2 diabetes
      complications.

PMID- 22361940
TI  - The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall
      associated phenolic glycolipids.
AB  - Phenolic glycolipids (PGLs) are non-covalently bound components of the outer
      membrane of many clinically relevant mycobacterial pathogens, and play important
      roles in pathogen biology. We report a mutational analysis that conclusively
      demonstrates that the conserved acyltransferase-encoding gene papA5 is essential
      for PGL production. In addition, we provide an in vitro acyltransferase activity
      analysis that establishes proof of principle for the competency of PapA5 to
      utilize diol-containing polyketide compounds of mycobacterial origin as acyl
      acceptor substrates. Overall, the results reported herein are in line with a
      model in which PapA5 catalyses the acylation of diol-containing polyketides to
      form PGLs. These studies advance our understanding of the biosynthesis of an
      important group of mycobacterial glycolipids and suggest that PapA5 might be an
      attractive target for exploring the development of antivirulence drugs.

PMID- 22361941
TI  - Suppression of pleiotropic phenotypes of a Burkholderia multivorans fur mutant by
      oxyR mutation.
AB  - Fur (ferric uptake regulator) is an iron-responsive transcriptional regulator in
      many bacterial species, and the fur mutant of Burkholderia multivorans ATCC 17616
      exhibits pleiotropic phenotypes, such as an inability to efficiently use several
      carbon sources, as well as high sensitivity to hydrogen peroxide (H(2)O(2)),
      paraquat (a superoxide-producing compound) and nitric oxide (NO). To gain more
      insight into the pleiotropic role of the Fur protein of ATCC 17616, spontaneous
      suppressor mutants of the ATCC 17616 fur mutant that restored tolerance to NO
      were isolated and characterized in this study. The microarray-based comparative
      genomic analysis and subsequent sequencing analysis indicated that such
      suppressor mutants had a 2 bp deletion in the oxyR gene, whose orthologues encode
      H(2)O(2)-responsive transcriptional regulators in other bacterial species. The
      suppressor mutants and the reconstructed fur-oxyR double-deletion mutant showed
      indistinguishable phenotypes in that they were all (i) more resistant than the
      fur mutant to H(2)O(2), superoxide, NO and streptonigrin (an iron-activated
      antibiotic) and (ii) able to use carbon sources that cannot efficiently support
      the growth of the fur mutant. These results clearly indicate that the oxyR
      mutation suppressed the pleiotropic effect of the B. multivorans fur mutant. The
      fur-oxyR double mutants were found to overexpress the KatG (catalase/peroxidase)
      and AhpC1 and AhpD (alkyl hydroperoxide reductase subunits C and D) proteins, and
      their enzymic activities to remove reactive oxygen and nitrogen species were
      suggested to be responsible for the suppression of phenotypes caused by the fur
      mutation.

PMID- 22361942
TI  - Expression of Vibrio vulnificus insulin-degrading enzyme is regulated by the cAMP
      CRP complex.
AB  - Components of the bacterial phosphoenolpyruvate (PEP) : carbohydrate
      phosphortransferase system (PTS) have multiple regulatory roles in addition to
      PEP-dependent transport/phosphorylation of numerous carbohydrates. We have
      recently shown that, in an opportunistic human pathogen, Vibrio vulnificus,
      enzyme IIA(Glc) (EIIA(Glc)) interacts with a peptidase that has high sequence
      similarity to mammalian insulin-degrading enzymes, called Vibrio insulin
      degrading enzyme (vIDE). Although the vIDE-EIIA(Glc) interaction is independent
      of the phosphorylation state of EIIA(Glc), vIDE shows no peptidase activity
      unless complexed with the unphosphorylated form of EIIA(Glc). A deletion mutant
      of ideV, the gene encoding vIDE, shows remarkably lower degrees of survival and
      virulence than the wild-type strain in mice, implying that vIDE is a virulence
      factor. In this study, we investigated regulation of ideV expression at the
      transcriptional level. Primer extension analysis identified two different
      transcriptional start sites of ideV: P(L) for the longer transcript and P(S) for
      the shorter transcript. We performed ligand fishing experiments by using the
      promoter region of ideV and found that the cAMP receptor protein (CRP)
      specifically binds to the promoter. DNase I footprinting experiments revealed
      that CRP binds to a region between the two promoters. In vitro transcription
      assays showed that CRP activates ideV P(S) transcription in the presence of cAMP
      whose concentration is regulated by EIIA(Glc). These results suggest that
      EIIA(Glc) regulates the expression level of vIDE as well as its activity.

PMID- 22361943
TI  - Long-term survival of Streptococcus pyogenes in rich media is pH-dependent.
AB  - The mechanisms that allow Streptococcus pyogenes to survive and persist in the
      human host, often in spite of antibiotic therapy, remain poorly characterized.
      Therefore, the determination of culture conditions for long-term studies is
      crucial to advancement in this field. Stationary cultures of S. pyogenes strain
      NZ131 and its spontaneous small-colony variant OK171 were found to survive in
      rich medium for less than 2 weeks, and this inability to survive resulted from
      the acidification of the medium to below pH 5.5, which the cells did not tolerate
      for longer than 6-7 days. The growth of NZ131 resulted in acidification of the
      culture to below pH 5.5 by the onset of stationary phase, and the loss of
      viability occurred in a linear fashion. These results were also found to be true
      for M49 strain CS101 and for M1 strain SF370. The S. pyogenes strains could be
      protected from killing by the addition of a buffer that stabilized the pH of the
      medium at pH 6.5, ensuring bacterial survival to at least 70 days. By contrast,
      increasing the glucose added to the medium accelerated the loss of culture
      viability in strain NZ131 but not OK171, suggesting that the small-colony variant
      is altered in glucose uptake or metabolism. Similarly, acidification of the
      medium prior to inoculation or at the middle of exponential phase resulted in
      growth inhibition of all strains. These results suggest that control of the pH is
      crucial for establishing long-term cultures of S. pyogenes.

PMID- 22361944
TI  - The ATPases CopA and CopB both contribute to copper resistance of the
      thermoacidophilic archaeon Sulfolobus solfataricus.
AB  - Certain heavy metal ions such as copper and zinc serve as essential cofactors of
      many enzymes, but are toxic at high concentrations. Thus, intracellular levels
      have to be subtly balanced. P-type ATPases of the P(IB)-subclass play a major
      role in metal homeostasis. The thermoacidophile Sulfolobus solfataricus possesses
      two P(IB)-ATPases named CopA and CopB. Both enzymes are present in cells grown in
      copper-depleted medium and are accumulated upon an increase in the external
      copper concentration. We studied the physiological roles of both ATPases by
      disrupting genes copA and copB. Neither of them affected the sensitivity of S.
      solfataricus to reactive oxygen species, nor were they a strict prerequisite to
      the biosynthesis of the copper protein cytochrome oxidase. Deletion mutant
      analysis demonstrated that CopA is an effective copper pump at low and high
      copper concentrations. CopB appeared to be a low-affinity copper export ATPase,
      which was only relevant if the media copper concentration was exceedingly high.
      CopA and CopB thus act as resistance factors to copper ions at overlapping
      concentrations. Moreover, growth tests on solid media indicated that both ATPases
      are involved in resistance to silver.

PMID- 22361945
TI  - Investigation of basement membrane proteins in a case of granular cell
      ameloblastoma.
AB  - Granular cell ameloblastoma is a rare, benign neoplasm of the odontogenic
      epithelium. A case of massive granular cell ameloblastoma in a 44-year-old Thai
      female is reported. Histopathological features displayed a follicular type of
      ameloblastoma with an accumulation of granular cells residing within the tumor
      follicles. After treatment by partial mandibulectomy, the patient showed a good
      prognosis without recurrence in a 2-year follow-up. To characterize the granular
      cells in ameloblastoma, we examined the expression of basement membrane (BM)
      proteins, including collagen type IV, laminins 1 and 5 and fibronectin using
      immunohistochemistry. Except for the granular cells, the tumor cells demonstrated
      a similar expression of BM proteins compared to follicular and plexiform
      ameloblastomas in our previous study, whereas the granular cells showed strong
      positivity to laminins 1 and 5 and fibronectin. The increased fibronectin
      expression in granular cells suggests a possibility of age-related transformation
      of granular cells in ameloblastoma.

PMID- 22361946
TI  - Prognostic and proliferative evaluation of ameloblastoma based on radiographic
      boundary.
AB  - Ameloblastoma is a benign odontogenic tumor with an aggressive biological
      behavior, and the surgical treatment frequently results in failure for the
      postoperative recurrence. The aim of this article was to investigate whether the
      proliferative ability and prognosis of ameloblastoma could be evaluated by the
      radiographic boundary. The ameloblastoma cases treated by the conservative
      therapy in our hospital between 1981 and 2001 were divided into three groups
      based on the nature of the radiographic borders of the lesions. The biologic
      behavior was evaluated by Ki-67 antibody immunohistochemically. Comparisons of
      prognosis and Ki-67 expression were carried out by statistic methods. There were
      24 cases of well-defined edge with sclerosis (group I), 41 cases of well-defined
      edge without sclerosis (group II) and 32 cases of ill-defined edge (group III).
      The recurrent rates were 29.2% in group I, 43.9% in group II and 62.5% in group
      III (P<0.05). The cells in group III expressed the highest Ki-67 level (P<0.05).
      The radiographic boundary could be used as one of indicators in evaluating the
      proliferative ability of ameloblastoma and the patient's prognosis, which was
      consistent with Ki-67 expression.

PMID- 22361947
TI  - Late-onset focal dermal elastosis.

PMID- 22361949
TI  - Summer happenings in Hematology 2011. Highlights in Hematological Malignancies
      form the 2011 American Society Clinical Oncology Annual Meeting and the 16th
      Congress of the European Hematology Association, and the 11th International
      Conference on Malignancy Lymphoma.

PMID- 22361948
TI  - Fine mapping of QTLs for rice grain yield under drought reveals sub-QTLs
      conferring a response to variable drought severities.
AB  - Fine-mapping studies on four QTLs, qDTY(2.1), qDTY(2.2), qDTY(9.1) and
      qDTY(12.1), for grain yield (GY) under drought were conducted using four
      different backcross-derived populations screened in 16 experiments from 2006 to
      2010. Composite and bayesian interval mapping analyses resolved the originally
      identified qDTY(2.1) region of 42.3 cM into a segment of 1.6 cM, the qDTY(2.2)
      region of 31.0 cM into a segment of 6.7 cM, the qDTY(9.1) region of 32.1 cM into
      two segments of 9.4 and 2.4 cM and the qDTY(12.1) region of 10.6 cM into two
      segments of 3.1 and 0.4 cM. Two of the four QTLs (qDTY(9.1) and qDTY(12.1))
      having effects under varying degrees of stress severity showed the presence of
      more than one region within the original QTL. The study found the presence of a
      donor allele at RM262 within qDTY(2.1) and RM24334 within qDTY(9.1) showing a
      negative effect on GY under drought, indicating the necessity of precise fine
      mapping of QTL regions before using them in marker-assisted selection (MAS).
      However, the presence of sub-QTLs together in close vicinity to each other
      provides a unique opportunity to breeders to introgress such regions together as
      a unit into high-yielding drought-susceptible varieties through MAS.

PMID- 22361950
TI  - Bite through the tent.
AB  - The authors report on a young boy who was bitten into his face by an unknown
      animal while being asleep in a tent. Given the bite marks and the location of the
      scene, members of the mustelidae and canidae families were the first "suspects."
      Deoxyribunucleic acid (DNA) recovered from the tent's wall was analyzed with
      regard to parts of the mitochondrial 12S ribosomal ribunucleic acid (12S rRNA)
      and cytochrome b (cytb) genes as well as nuclear short tandem repeats (STRs).
      Since Sanger sequencing revealed a mixed sequence with a strong human component
      overlying the nonhuman contributor, an animal screening using a duplex real-time
      polymerase chain reaction (PCR) with an intercalating dye and melt curve analysis
      was employed. The results were later confirmed by cloning. The applied commercial
      canine STR kit verified the animal family (canidae) but did not help in
      discriminating the species due to cross-species amplification. In the presented
      case, the real-time PCR assay offered the cheapest and fastest method for animal
      family determination, which then allowed for an appropriate and sample-saving
      strategy to characterize the causative animal species.

PMID- 22361951
TI  - Immunohistochemical detection of uPA, tPA, and PAI-1 in a stasis-induced deep
      vein thrombosis model and its application to thrombus age estimation.
AB  - We immunohistochemically examined the expression of urokinase-type plasminogen
      activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen
      activator inhibitor type-1 (PAI-1) using venous thrombi developed by ligation of
      the inferior vena cava (IVC) in mice. The uPA-, tPA- and PAI-1-positive cells
      could be firstly detected 5, 7, and 3 days, respectively, after IVC ligation.
      Morphometrically, the number of PAI-1-positive cells was significantly higher
      than those of uPA- and tPA-positive cells at later than 7 days. In all of the
      thrombus samples aged 10-21 days, the uPA/PAI-1 and tPA/PAI-1 ratios were >0.1
      and >0.2, respectively. In contrast, all of the thrombus samples aged 1-7 days
      had uPA/PAI-1 of <0.1 and tPA/PAI-1 ratios of <0.2. These findings implied that
      uPA/PAI-1 of >0.1 and tPA/PAI-1 of >0.2 indicated an age of 10 days or more.
      Moreover, in four of five samples aged 10 days, uPA/PAI-1 ratios were <0.3, and
      the remaining one had uPA/PAI-1 of 0.32. All thrombi aged 14-21 days showed
      values greater than 0.3. Thus, uPA/PAI-1 ratios, markedly exceeding 0.3, strongly
      indicated an age of more than 14 days. The present study demonstrated that the
      immunohistochemical detection of uPA, tPA, and PAI-1 was suitable to estimate the
      age of venous thrombi.

PMID- 22361953
TI  - An analytical expression for the van der Waals interaction in oriented-attachment
      growth: a spherical nanoparticle and a growing cylindrical nanorod.
AB  - A mathematical derivation of an analytical expression is presented to evaluate
      the van der Waals interaction between a sphere and a cylindrical rod. This
      expression then is applied to study the growth of one-dimensional nanostructures,
      such as nanorods, using a common growth mechanism in colloidal chemistry, the
      oriented attachment growth mechanism. Parameters associated with the dimensions
      and the separation of nanoparticles and nanorods are varied in calculations to
      assess their influence on the magnitude of the van der Waals interaction.

PMID- 22361952
TI  - Apoptotic sperm biomarkers and their correlation with conventional sperm
      parameters and male fertility potential.
AB  - PURPOSE: To investigate the relationship between sperm apoptotic biomarkers and
      patient clinical characteristics, conventional sperm parameters and fertility
      potential. MATERIAL AND METHODS: Sperm analysis, phospholipid asymmetry,
      mitochondrial membrane potential (MMP) and DNA denaturation were assessed in 142
      males of infertile couples. Seventy-three couples were allocated to the natural
      conception group, and 55 couples underwent IVF or ICSI. RESULTS: DNA denaturation
      correlated positively with age and negatively with testicular volume (TV). MMP
      correlated negatively with BMI and FSH and positively with TV. Normal viable
      sperm correlated positively with TV and negatively with age, BMI and FSH. DNA
      denaturation was associated with a significantly lower natural pregnancy rate (OR
      5.4, 95% CI:1.3-22, p = 0.011). CONCLUSION: Sperm apoptosis is related to male
      age, BMI, testicular volume and FSH. Among the apoptotic markers, only DNA
      denaturation has been found to predict natural pregnancy better than conventional
      sperm parameters.

PMID- 22361954
TI  - Acid-base balance and metabolic response of the sea urchin Paracentrotus lividus
      to different seawater pH and temperatures.
AB  - PURPOSE: In order to better understand if the metabolic responses of echinoids
      could be related to their acid-base status in an ocean acidification context, we
      studied the response of an intertidal sea urchin species, Paracentrotus lividus,
      submitted to low pH at two different temperatures. METHODS: Individuals were
      submitted to control (8.0) and low pH (7.7 and 7.4) at 10 degrees C and 16
      degrees C (19 days). The relation between the coelomic fluid acid-base status,
      the RNA/DNA ratio of gonads and the individual oxygen uptake were studied.
      RESULTS: The coelomic fluid pH decreased with the aquarium seawater,
      independently of temperature, but this explained only 13% of the pH variation.
      The coelomic fluid showed though a partial buffer capacity that was not related
      to skeleton dissolution ([Mg(2+)] and [Ca(2+)] did not differ between pH
      treatments). There was an interaction between temperature and pH on the oxygen
      uptake (V (O2)) which was increased at pH 7.7 and 7.4 at 10 degrees C in
      comparison with controls, but not at 16 degrees C, indicating an upregulation of
      the metabolism at low temperature and pH. However, gonad RNA/DNA ratios did not
      differ according to pH and temperature treatments, indicating that even if
      maintenance of physiological activities has an elevated metabolic cost when
      individuals are exposed to stress, they are not directly affected during short
      term exposure. Long-term studies are needed in order to verify if gonad
      production/growth will be affected by low pH seawaters exposure.

PMID- 22361955
TI  - Eye movements and the perceptual span in silent and oral reading.
AB  - Previous research has examined parafoveal processing during silent reading, but
      little is known about the role of these processes in oral reading. Given that
      masking parafoveal information slows down silent reading, we asked whether a
      similar effect also occurs in oral reading. To investigate the role of parafoveal
      processing in silent and oral reading, we manipulated the parafoveal information
      available to readers by changing the size of a gaze-contingent moving window.
      Participants read silently and orally in a one-word window and a three-word
      window condition as we monitored their eye movements. The lack of parafoveal
      information slowed reading speed in both oral and silent reading. However, the
      effects of parafoveal information were larger in silent reading than in oral
      reading, because of different effects of preview information on both when the
      eyes move and how often. Parafoveal information benefitted silent reading for
      faster readers more than for slower readers.

PMID- 22361956
TI  - Fabrication of quasiperiodic nanostructures with EUV interference lithography.
AB  - We demonstrate the fabrication and analysis of well-ordered high-resolution
      quasiperiodic nanostructures with feature sizes down to a few tens of nanometers
      using extreme ultraviolet interference lithography. A well-controlled mask
      manufacturing process for producing high quality transmission diffraction masks
      enables simple and fast fabrication of highly ordered 2D quasiperiodic structures
      using 5- and 8-beam interference setups.

PMID- 22361957
TI  - A case of squamous cell carcinoma of the scalp after several synthetic hair
      grafts.
AB  - In the early 1970s a novel method for hair restoration was described and gained a
      large following: hair implantation of artificial synthetic fibers. Though
      popular, the procedure faced numerous criticisms from the scientific community by
      the early 1980s, and several major and minor complications in a large number of
      patients treated were reported. However, there were no reports of any neoplasms
      as complications of artificial hair implantation. Thus, we report our experience
      with a novel case of long-term cutaneous neoplastic degeneration of an artificial
      hair implantation procedure in order to provide new insight on the complications
      related to this procedure. 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 at http://www.springer.com/00266.

PMID- 22361958
TI  - Anatomical evaluation of facial nerve pathways and dissection of "premasseter
      space" for rhytidectomy in Asians.
AB  - BACKGROUND: Partial detachment of the superficial musculoaponeurotic system
      (SMAS) by dissection of the premasseter space (PMS) is an option for enhancing
      the effectiveness of SMAS-based rhytidectomy. The aim of this study was to
      identify the underlying cause of the potential risk of motor nerve impairment
      sometimes caused by PMS dissection and to consider the effective use of PMS
      dissection, especially in Asians. METHODS: Detailed dissection was carried out on
      six fixed Japanese cadavers to evaluate facial nerve pathways around the PMS.
      RESULTS: The anterior wall of the PMS was opaque because each face exhibited
      fibers of various thicknesses within and around the anterior border of the
      masseter. The ascending ramifications of the buccal trunk ran through the fibers,
      outside the anterior border of the masseter in some faces but within it in
      others. CONCLUSIONS: This study revealed the presence of a danger zone when
      dissecting the PMS in Asians. Severing the fibers that fix the SMAS to the
      masseter fascia around the anterior border of the masseter is sometimes
      unavoidable to attain good mobility of the SMAS. Surgeons must be mindful of the
      fibers near the anterior border of the masseter because they may be outside the
      PMS and contain buccal trunk ramifications; the anterior wall of the PMS tends to
      be opaque in Asians. Nonetheless, the extent of PMS dissection should be
      determined on an individual basis. The present findings may help to reduce
      relevant risks in Asian patients and standardize procedures for effective
      rhytidectomy. 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 at www.springer.com/00266.

PMID- 22361959
TI  - The role of MRI in spinal stab wounds compared with intraoperative findings.
AB  - INTRODUCTION: Spinal stab wound injuries are quite rare and only few patients
      have been reported on the basis of MRI scan. METHODS: A 25-year-old man was
      stabbed at C1/2 and had an incomplete Brown-Sequard syndrome. He underwent
      surgical exploration because of CSF leakage on the fourth day. RESULTS: After a
      follow-up period of 32 months, he was left with a remaining loss of the
      proprioception of the right foot. We show detailed CT and MR images with the
      focus on the lesions of the dura and myelon and compared them with intraoperative
      images. In addition, we contrast our findings with a review of literature
      published over the last three decades. CONCLUSION: MRI gives the most detailed
      view of soft tissue lesions in SSWs and is in accordance with our intraoperative
      findings.

PMID- 22361960
TI  - Pedicle subtraction osteotomy in degenerative scoliosis.

PMID- 22361961
TI  - Pedicle subtraction osteotomy in flat back syndrome 38 years after Harrington
      instrumentation for AIS.

PMID- 22361962
TI  - Promiscuous esterase activities of the C-C hydrolases from Dyella ginsengisoli.
AB  - A C-C hydrolase gene (bphD(LA-4)) from strain Dyella ginsengisoli LA-4 was cloned
      and expressed in Escherichia coli BL21 (DE3). BphD(LA-4) together with another
      hydrolase MfphA(LA-4), which derived from the same strain, possessed esterase
      activities. p-Nitrophenyl butyrate was the best substrate for both enzymes.
      BphD(LA-4) had high catalytic efficiency to p-nitrophenyl benzoate, whereas
      MfphA(LA-4) had no activity. Homology modeling and docking studies demonstrated
      that the proper hydrogen bond interaction was important for the reactivity of
      specific substrate.

PMID- 22361963
TI  - Osteochondral regeneration by a bilayered construct in a cell-free or cell-based
      approach.
AB  - A bilayered construct with or without adipose-derived stem cells (ASCs) was
      applied to repair full-thickness defects in the patellar groove of 18 rabbits.
      Non-treated and treated defects were divided into three groups: a control group
      (n = 12), a cell-free group (n = 12) and a cell-based group (n = 12).
      Histological appearance and grading were evaluated at 8 and 12 weeks. At 12
      weeks, osteochondral-like tissues completely filled in the defects and integrated
      with host tissues in the cell-based group. The semi-quantitative score of the
      cell-based group (4.2 +/- 1.2), which is a total score ranging from 0 (best) to
      20 (worst), was significantly better than that of the other two groups (cell
      free: 13.8 +/- 2.5; control: 10.3 +/- 2.4). This finding indicated that the
      bilayered constructs combined with ASCs could be an effective way to enhance
      osteochondral regeneration.

PMID- 22361964
TI  - An electrochemical method for functionalization of a 316L stainless steel surface
      being used as a stent in coronary surgery: irreversible immobilization of
      fibronectin for the enhancement of endothelial cell attachment.
AB  - An electrochemistry-based method for the formation of functionalized alkanethiol
      layers on a 316L stainless steel surface was developed. The method was efficient
      in forming a very stable, irreversibly-attached COOH-terminated
      (mercaptoundecanoic acid) surface layer. This layer was used as a 'linker' to
      immobilize the extracellular matrix protein fibronectin to the 316L stainless
      steel surface. Fibronectin was irreversibly attached to the surface and, unlike
      physisorbed fibronectin, resisted detachment more in aggressive 0.1 M NaOH under
      sonication. The fibronectin-modified 316L stainless steel surface was more
      biocompatible towards attachment of endothelial cells than a bare (unmodified)
      316L stainless steel surface, yielding a 25% improvement in cell density.

PMID- 22361965
TI  - A hydrophilic and hydrophobic organic solvent mixture enhances enzyme stability
      in organic media.
AB  - Binary mixtures of hydrophilic and hydrophobic solvents were assessed for their
      ability to balance enzyme activity with the conservation of enzyme stability in
      organic media. Acetone, dioxane and dodecane were chosen as model organic
      solvents, and subtilisin Carlsberg and horseradish peroxidase (HRP) were chosen
      as model enzymes. Residual enzyme activities were measured to monitor enzyme
      stability, and the fluorescence intensity of HRP was monitored to investigate
      structural changes due to the presence of an organic solvent. Enzyme stability
      increased with the increasing hydrophobicity of the solvent mixture used, and a
      solvent mixture with a high log P value (~ >4) was capable of conserving enzyme
      stability. Enzyme stability in organic media can be conserved therefore with a
      mixture of hydrophilic and hydrophobic solvents: this approach might be used as a
      general and practical strategy for optimizing enzyme activity and stability for
      industrial applications.

PMID- 22361967
TI  - Novel saccharinate-bridged palladium complexes for efficient C-O bond activation
      displaying promising luminescence properties.
AB  - The synthesis of mono- and dinuclear cyclometallated palladium(II) complexes with
      deprotonated saccharinate ligands displaying different coordination modes is
      described. The new compounds were prepared by direct reaction between saccharine
      and the corresponding hydroxo-complexes [{Pd(MU-OH)(C^N)}(2)] (C^N = 2-(2
      pyridyl)phenyl (Phpy) I; = 7,8-benzoquinolyl (Bzq) II), showing a general formula
      [{Pd(MU-sac)(C^N)}(2)] with saccharinate 1 displaying a bridging -NCO
      coordination mode. Bridge splitting with neutral ligands (L = pyridine (py) 2,
      quinoline (quinol) 3 or acridine (acrid) 4) yielded new mononuclear derivatives
      with saccharinate acting as an N-monodentated ligand. Structural characterization
      by X-ray diffraction of complexes I1, I2 and II2 confirmed the proposed formulae.
      All complexes emit in the solution and solid state at room temperature. Emission
      features between 640-680 nm in the solid state for complexes I1 and II1 are
      significantly red-shifted if compared to the emission in solution. These broad
      emissions are consistent with the simultaneous presence of (3)pipi* and (3)MMLCT
      transitions indicating the existence of a strong intramolecular Pd-Pd ground
      state interaction. The dimeric complexes have also shown to catalyze Suzuki
      Miyaura cross-coupling of coumaryl tosylate and aryl boronic acids under
      phosphine-free conditions. Initial studies suggest the involvement of palladium
      nanoparticles, which has been further investigated using mercury-drop test and
      poisoning experiments.

PMID- 22361968
TI  - Neuroanesthesiology update.
AB  - With a focus on landmark investigations, common themes, and unique and innovative
      contributions to the literature, we provide a synopsis of the 2011 literature
      pertaining to general advances in neurosurgical procedures and perioperative care
      and anesthetic management of neurosurgical patients.

PMID- 22361969
TI  - Amyloidomics comes of age.
AB  - Potentially effective and life-saving treatment for patients with systemic
      amyloidosis relies on the astute clinician recognizing the signs and symptoms,
      histochemical identification of fibrils, and accurate diagnosis of amyloid type.
      In this issue of Blood, Brambilla et al report a new methodology for
      accomplishing the key third step in this process.

PMID- 22361970
TI  - Hydroxyurea makes inflammation "just right"?
AB  - Hydroxyurea treatment of sickle cell mice improved their survival from
      pneumococcal pneumonia, counteracting the abnormally elevated inflammatory
      response and reducing invasion of bacteria into the bloodstream, through down
      regulation of E-selectin.

PMID- 22361971
TI  - "Radical" model of thrombosis.
AB  - In this issue of Blood, Nishimura and colleagues present a novel in vivo murine
      model of thrombosis triggered on the undisrupted, activated endothelium in
      response to reactive oxygen species (ROS)-producing free radicals derived from
      oxygen (namely O(2)(-)), which can be present in the vasculature as a result of
      inflammation (see figure). This new in vivo model involving a novel injury,
      minimally invasive vessel preparation, and advanced data collection may be
      particularly useful in dissecting the role of inflammation in thrombosis.

PMID- 22361973
TI  - A simple method to fabricate electrochemical sensor systems with predictable high
      redox cycling amplification.
AB  - In this paper an easy to fabricate SU8/glass-based microfluidic sensor is
      described with two closely spaced parallel electrodes for highly selective
      measurements using the redox cycling effect. By varying the length of the
      microfluidic entrance channel, a diffusion barrier is created for non-cycling
      species effectively increasing selectivity for redox cycling species. Using this
      sensor, a redox cycling amplification of ~6500* is measured using the
      ferrocyanide redox couple. Moreover, a simple, but accurate analytical expression
      is derived that predicts the amplification factor based on the sensor geometry.

PMID- 22361974
TI  - A triphenylene based zinc ensemble as an oxidation inhibitor.
AB  - The zinc complex of a new triphenylene based receptor is evaluated for its anti
      oxidant activity which is better in comparison to that of commercially available
      anti-oxidants.

PMID- 22361975
TI  - Obstructive sleep apnea and pregnancy: the effect on perinatal outcomes.
AB  - Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper
      airway obstruction, resulting in hypoxemia, hypercapnia and sleep fragmentation.
      Pathophysiological sequelae include sympathetic activation, increased oxidative
      stress and a generalized inflammatory response, culminating in endothelial
      dysfunction. These are the proposed mechanisms that mediate the increased risk of
      hypertension and cardiovascular disease among patients with OSA outside of
      pregnancy. It is intriguing to consider the consequences of these events on
      pregnancy outcomes. There is a growing literature on the impact of maternal OSA
      on hypertensive disorders of pregnancy, gestational diabetes and impaired fetal
      growth. The data, while promising, require confirmation with larger numbers to
      verify the findings. OSA may be an important mediator of the poor perinatal
      outcomes associated with maternal obesity; moreover, one which may be amenable to
      treatment. This review discusses OSA and summarizes the current literature
      linking OSA with adverse perinatal outcomes.

PMID- 22361976
TI  - Post-operative guidelines following hip arthroscopy.
AB  - Rehabilitation following hip arthroscopy can vary significantly. Existing
      programs have been developed as a collaborative effort between physicians and
      rehabilitation specialists. The evolution of protocol advancement has relied upon
      feedback from patients, therapists and observable outcomes. Although reports of
      the first femoroacetabular impingement (FAI) surgeries were reported in the
      1930's, it was not until recently that more structured, physiologically based
      guidelines have been developed and executed. Four phases have been developed in
      this guideline based on functional and healing milestones achieved which allow
      the patient to progress to the next level of activity. The goal of Phase I, the
      protective phase, is to progressively regain 75% of full range of motion (ROM)
      and normalize gait while respecting the healing process. The primary goal of
      Phase II is for the patient to gain function and independence in daily activities
      without discomfort. Rehabilitation goals include uncompensated step up/down on an
      8 inch box, as well as, adequate pelvic control during low demand exercises.
      Phase III goals strive to accomplish pain free, non-compensated recreational
      activities and higher demand work functions. Manual muscle testing (MMT) grading
      of 5/5 should be achieved for all hip girdle musculature and an ability to
      dynamically control body weight in space. Phase IV requires the patient be
      independent with home and gym programs and be asymptomatic and pain free
      following workouts. Return to running may be commenced at the 12 week mark, but
      the proceeding requirements must be achieved. Athletes undergoing the procedure
      may have an accelerated timetable, based on the underlying pathology. Recognizing
      the patient's pre-operative health status and post-operative physical demands
      will direct both the program design and the program timetable.

PMID- 22361977
TI  - Brain biopsy in benign neurological disease.
AB  - Brain biopsy is well established in clinical practice when there is suspicion of
      CNS malignancy. However, there is little consensus regarding the indications for
      brain biopsy in non-malignant neurological disease. This is due in no small part
      to limitations in the available literature pertaining to diagnostic brain
      biopsies. The published evidence largely comprises small, retrospective, single
      centre analyses performed over long time periods, including non-homogeneous
      patient groups with considerable variation in reported outcomes. Here we present
      pragmatic guidance for those clinicians considering diagnostic brain biopsy in a
      patient with non-neoplastic neurological disease and highlight practice points
      with the aim of maximising the probability of gaining clinically useful
      information from the procedure.

PMID- 22361979
TI  - Oculomucosal and gastrointestinal involvement in Epstein-Barr virus-associated
      hydroa vacciniforme.
AB  - In a series of patients with Epstein-Barr virus (EBV)-associated hydroa
      vacciniforme (HV) and related disorders, we reviewed the incidence of
      oculomucosal and gastrointestinal involvement. Of 63 patients with EBV-related HV
      and/or hypersensitivity to mosquito bites (HMB), 11 patients (17.5%) presented
      with mucosal lesions such as aphthous stomatitis and ulcerative gingivitis, 3
      patients (4.8%) had ocular symptoms including iritis, conjunctival hyperemia and
      corneal erosions, and 2 patients (3.2%) presented with severe HV complicated
      gastrointestinal involvement. Oculomucosal lesions are sometimes complicated in
      patients with EBV-related HV and HMB, and gastrointestinal involvement may occur
      in the severe form.

PMID- 22361980
TI  - Highlights in NSCLC from the American Society of Clinical Oncology Meeting, June
      3-7, 2011, Chicago, Illinois, USA.

PMID- 22361978
TI  - The spectrum of clinicopathological features in pure autonomic neuropathy.
AB  - We assessed the clinicopathological features of nine patients with pure autonomic
      neuropathy, that is, neuropathy without sensory or motor deficits. The duration
      from symptom onset to diagnosis ranged from 1 month to 13 years. Of eight
      patients in whom serum antiganglionic acetylcholine receptor antibody was
      determined, four were positive. All patients who tested positive for this
      antibody manifested widespread autonomic dysfunction, with the exception of one
      patient who only experienced orthostatic hypotension. However, patients who were
      negative for the antiganglionic acetylcholine receptor antibody presented with
      partial autonomic failure. One of these patients had diffuse parasympathetic
      failure and generalized hypohidrosis but no orthostatic hypotension, which is
      clinically compatible with postganglionic cholinergic dysautonomia. Electron
      microscopic examination revealed a variable degree of reduction in unmyelinated
      fibers. Compared with normal controls, the patients had a significantly increased
      density of collagen pockets (p < 0.05). Additionally, the percentage of Schwann
      cell subunits with axons (out of the total number of Schwann cell subunits
      associated with unmyelinated fibers) was significantly decreased (p < 0.01). The
      density of unmyelinated fibers tended to decrease with increasing time between
      the onset of autonomic symptoms and biopsy (p < 0.05). In conclusion, the
      clinical and pathological features of pure autonomic neuropathy vary in terms of
      progression, autonomic involvement, presence of the antiganglionic acetylcholine
      receptor antibody, and loss of unmyelinated fibers.

PMID- 22361982
TI  - Treatment of acute Charcot foot with bisphosphonates: a systematic review of the
      literature.
AB  - AIM/HYPOTHESIS: We undertook a systematic review of the literature concerning the
      efficacy and safety of bisphosphonates in acute Charcot neuropathic
      osteoarthropathy. METHODS: MEDLINE, PubMed, the Cochrane Database of Systematic
      Reviews, and abstracts presented during the meetings of the American Diabetes
      Association and the European Association of Diabetes were searched for relevant
      publications from the period January 1990 to September 2011. RESULTS: A total of
      ten studies on the treatment of acute Charcot osteoarthropathy with
      bisphosphonates were identified and included in the analysis. Only four clinical
      trials were published, three of which were randomised. Bisphosphonates appeared
      to induce significant reductions in skin temperature and bone turnover markers
      compared with placebo, without serious adverse events. Nevertheless,
      bisphosphonates did not shorten the immobilisation time. Moreover, no data were
      available regarding their long-term effects. CONCLUSIONS/INTERPRETATIONS:
      Bisphosphonates have been shown to be effective for reducing bone turnover
      markers and skin temperature in some studies. Nevertheless, the long-term
      efficacy, specifically that regarding the occurrence of deformities and
      ulcerations, remains to be demonstrated as no follow-up studies have been
      published. Moreover, some studies have suggested that bisphosphonates may
      lengthen the resolution phase of the disease. In our opinion, the data are too
      weak to support the use of bisphosphonates as a routine treatment for acute
      Charcot neuroarthropathy.

PMID- 22361981
TI  - Arm length is associated with type 2 diabetes mellitus in Japanese-Americans.
AB  - AIMS/HYPOTHESIS: The aim of the study was to examine the association of type 2
      diabetes mellitus with arm length as a marker for early life environment and
      development. METHODS: This was a cross-sectional analysis of 658 second- and
      third-generation Japanese-Americans (349 men and 309 women). Different arm length
      (total, upper and forearm length) and leg length (total and lower leg length)
      measurements were performed. Type 2 diabetes was defined by the use of
      hypoglycaemic medication, fasting plasma glucose (FPG) >= 7 mmol/l or glucose at
      2 h >= 11.1 mmol/l during an OGTT. Persons meeting the criteria for impaired
      glucose tolerance were excluded from these analyses (FPG <7 mmol/l and 2 h
      glucose during an OGGT <11.1 but >= 7.8 mmol/l). Multivariable logistic
      regression was used to estimate associations between prevalence of diabetes and
      limb length while adjusting for possible confounders. RESULTS: A total of 145
      individuals had diabetes. On univariate analysis, arm and leg length were not
      associated with diabetes. After adjustment for age, sex, computed tomography
      measured intra-abdominal fat area, height, weight, smoking status and family
      history of diabetes, total arm length and upper arm length were inversely related
      to diabetes (OR for a 1 SD increase 0.49, 95% CI 0.29, 0.84 for total arm length,
      and OR 0.56, 95% CI 0.36, 0.87 for upper arm length). Forearm length, height and
      leg length were not associated with diabetes after adjustment for confounding
      variables. CONCLUSIONS/INTERPRETATION: Our findings of associations between arm
      lengths and prevalence of type 2 diabetes supports a role for factors that
      determine bone growth or their correlates in the development of this condition.

PMID- 22361983
TI  - The interaction of His337 with the Mn4Ca cluster of photosystem II.
AB  - The most recent XRD studies of Photosystem II (PS II) reveal that the His337
      residue is sufficiently close to the Mn(4)Ca core of the Water Oxidising Complex
      (WOC) to engage in H-bonding interactions with the MU(3)-oxo bridge connecting
      Mn(1), Mn(2) and Mn(3). Such interactions may account for the lengthening of the
      Mn-Mn distances observed in the most recent and highest resolution (1.9 A)
      crystal structure of PS II compared to earlier, lower-resolution (2.9 A or
      greater) XRD structures and EXAFS studies on functional PS II. Density functional
      theory is used to examine the influence on Mn-Mn distances of H-bonding
      interactions, mediated by the proximate His337 residue, which may lead to either
      partial or complete protonation of the MU(3)-oxo bridge on models of the WOC.
      Calculations were performed on a set of minimal-complexity models (in which WOC
      ligating amino acid residues are represented as formate and imidazole ligands),
      and also on extended models in which a 13-peptide sequence (from His332 to
      Ala344) is treated explicitly. These calculations demonstrate that while the 2.9
      A structure is best described by models in which the MU(3)-oxo bridge is neither
      protonated nor involved in significant H-bonding, the 1.9 A XRD structure is
      better reproduced by models in which the MU(3)-oxo bridge undergoes H-bonding
      interactions with the His337 residue leading to expansion of the 'close' Mn-Mn
      distances well known from EXAFS studies at ~ 2.7 A. Furthermore, full MU(3)-oxo
      bridge protonation remains a distinct possibility during the process of water
      oxidation, as evidenced by the lengthening of the Mn-Mn vectors observed in EXAFS
      studies of the higher oxidation states of PS II. In this context, the Mn-Mn
      distances calculated in the protonated MU(3)-oxo bridge structures, particularly
      for the peptide extended models, are in close agreement with the EXAFS data.

PMID- 22361984
TI  - The effect of question order on evaluations of test performance: how does the
      bias evolve?
AB  - Weinstein and Roediger (Memory & Cognition 38:366-376, 2010) found that
      manipulating the order of questions on a general knowledge quiz resulted in
      differing evaluations of performance at the end of the quiz: Irrespective of
      their actual performance, participants were consistently more optimistic about
      their performance when questions were given in an easy-to-hard order. In the
      present experiment, the participants were stopped 10 times throughout a 100-item
      test and asked to evaluate their performance on the last 10 questions they had
      answered, as well as rating their impressions of the test so far and predicting
      their final performance. Arranging the questions from the easiest to the hardest
      produced more optimistic performance evaluations on each block than did an
      analogous hard-easy question order, even though performance on the two versions
      did not differ significantly as a function of question order. Furthermore, the
      ratings of item difficulty on each block of 10 questions were asymmetrical in the
      two conditions, with a higher sensitivity to increasing as compared to decreasing
      question difficulty. On the other hand, the item-by-item ratings and predictions
      remained unaffected by question order. Our findings are best explained by an
      anchoring interpretation, which suggests that students fail to adjust their
      evaluations of performance as the difficulty of the questions changes across the
      test.

PMID- 22361985
TI  - Silica coating of polymer nanowires produced via nanoimprint lithography from
      femtosecond laser machined templates.
AB  - In this paper we report on the fabrication of regular arrays of silica
      nanoneedles by deposition of a thin layer of silica on patterned arrays of
      polymer nanowires (or polymer nanohair). An array of high-aspect-ratio nanoscale
      diameter holes of depths greater than 10 um was produced at the surface of a
      fused silica wafer by an amplified femtosecond laser system operated in single
      pulse mode. Cellulose acetate (CA) film was imprinted into the nanoholes and
      peeled off to form a patterned array of standing CA nanowires, a negative replica
      of the laser machined nanoholes. The cellulose acetate replica was then coated
      with silica in a chemical vapor deposition process using silicon tetrachloride
      vapor at 65  degrees C. Field emission scanning electron microscopy, focused ion
      beam sectioning, energy dispersive x-ray analysis and Fourier-transform infrared
      spectroscopy were used to characterize the silica nanoneedles. Precisely
      patterned, functionalized arrays of standing silica nanoneedles are useful for a
      number of applications.

PMID- 22361986
TI  - Evolution of proviral DNA HIV-1 tropism under selective pressure of maraviroc
      based therapy.
AB  - OBJECTIVES: To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA
      of patients during maraviroc-based therapy. METHODS: Fourteen heavily high active
      antiretroviral therapy (HAART)-treated patients with a CCR5 Trofile profile were
      monitored over a 24 month period from the start of maraviroc therapy. Whole-blood
      samples were obtained at different timepoints, and coreceptor tropism was
      determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno
      algorithm [false positive rate (FPR): 20%]. RESULTS: At the start of maraviroc
      treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance
      in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV
      DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a
      CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%,
      respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two
      out of four R5/X4 patients showed a tropism shift in their archived provirus and,
      after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two
      R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in
      provirus during the study. Virological response did not reveal differences in RNA
      decay and CD4+ cell recovery in patients with discordant tropism. CONCLUSIONS: A
      relatively good correlation between RNA and DNA tropism was observed at baseline.
      Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy,
      indicating that determination of proviral DNA V3 sequence could be used in
      tropism prediction in clinical practice. The data also confirm the importance of
      the 11/25 rule in predicting viral tropism.

PMID- 22361987
TI  - Intra-aortic balloon pump for hemodynamic support in hepatobiliary surgery:
      report of a case.
AB  - The intra-aortic balloon pump (IABP) can be used transiently to improve cardiac
      function mechanically, in patients with severe cardiomyopathy and heart failure
      refractory to medical therapy. In the field of surgery, the IABP is most commonly
      used for patients with myocardial infarction, congestive heart failure, or other
      chronic cardiac conditions, who are undergoing cardiac surgery. Conversely, it is
      rarely used in hepatobiliary surgery, with only two reports found in the
      literature, excluding cases of emergency cholecystectomy. We describe how we used
      an IABP successfully during surgery to repair a transected bile duct in a patient
      with peripartum cardiomyopathy.

PMID- 22361988
TI  - Moderating effects of leisure-time physical activity on the association between
      job strain and depressive symptoms: the Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVE: We examined whether long-term leisure-time physical activity (LTPA)
      has a moderating effect on the association between job strain and depressive
      symptoms using prospective data. METHODS: Full-time employees (455 men and 480
      women) aged 30 to 45 years were followed from 2001 to 2007. Data were collected
      using questionnaires. RESULTS: Sustained participation in LTPA was inversely
      associated with depressive symptoms in employed men and women. The direct
      relationship of job strain to depressive symptoms was significantly moderated by
      LTPA only in women when the potential confounders were controlled for.
      CONCLUSIONS: Depressive symptoms are inversely associated with regular LTPA and
      directly associated with chronic job strain in both sexes. In women, persistent
      participation in LTPA may modify the relation between chronic job stress and
      subthreshold depressive symptoms by reducing depressive symptoms associated with
      job strain.

PMID- 22361989
TI  - Identification of work-related injuries in a State Trauma Registry.
AB  - OBJECTIVE: Many state trauma registries contain work-related information but are
      underutilized for occupational injury research/surveillance. We assessed three
      methods of identifying work-related injuries in the Washington State Trauma
      Registry (WTR). METHODS: State-designated trauma facilities report traumatic
      injuries meeting specific inclusion criteria to the WTR. The WTR reports from
      1998 to 2008 were linked to workers' compensation claims to generate sensitivity
      estimates. RESULTS: The sensitivity of the WTR work-related indicator was 87%,
      varying significantly by injury mechanism/location. Sensitivity was 89% for payer
      and 60% for an indicator based on International Classification of Diseases-9th
      Revision-Clinical Modification external cause codes. CONCLUSIONS: The WTR work
      related indicator is highly sensitive and may identify injuries that occur in the
      course of exempt/excluded employment, are not reported to workers' compensation,
      and/or are work-related using definitions that go beyond WC coverage. Judicious
      use of external cause codes may identify additional work-related injuries.

PMID- 22361990
TI  - Mortality from cancer and other causes in an Italian cohort of male rubber tire
      workers.
AB  - OBJECTIVE: To investigate mortality among workers of an Italian rubber tire
      factory employed between 1954 and 2008. METHODS: This cohort study included 6246
      men, totaling 190,512 man-years of observation. Employment data were obtained
      from personnel records, whereas vital status and causes of death were ascertained
      from local authorities. We computed standardized mortality ratios (SMRs) using
      national and regional death certification rates. RESULTS: Mortality was
      significantly lower than expected for all cancers (SMR = 79) and all causes (SMR
      = 85). The SMRs were 99 for cancer of stomach, 78 for lung, 121 for urinary
      bladder, 116 for lymphoma, and 89 for leukemia, none being significant. Decreased
      mortality emerged for cancers of the oral cavity and pharynx (SMR = 45),
      esophagus (SMR = 29), colorectum (SMR = 71), liver (SMR = 57), and kidney (SMR =
      33). CONCLUSIONS: This study shows no excess cancer risk among male rubber tire
      workers employed after 1954.

PMID- 22361991
TI  - Is an occupational examination superior to an occupational health history alone
      for preplacement screening in health care settings?
AB  - OBJECTIVES: To determine whether preplacement recommendations following an
      occupationally focused medical history is different from those following an
      occupational consultation. METHODS: This was a retrospective cohort study of 172
      applicants to our institution. RESULTS: Following provider review of occupational
      history survey alone, none of the applicants had restrictions recommended. In
      comparison, only 163 applicants (94.7%) were recommended to be hired without
      restrictions following provider review of the same patient's occupational history
      and examination (P = 0.0078). CONCLUSION: A well-designed questionnaire is useful
      for screening applicants for preplacement examinations and assures sufficient
      detail to allow for a large proportion of individuals to proceed to employment
      without an occupational examination. However, in this study, a small but
      statistically significant portion (5%) of applicants required occupational
      examinations for appropriate work recommendations.

PMID- 22361992
TI  - The effects of incremental costs of smoking and obesity on health care costs
      among adults: a 7-year longitudinal study.
AB  - OBJECTIVE: To provide the simultaneous 7-year estimates of incremental costs of
      smoking and obesity among employees and dependents in a large health care system.
      METHODS: We used a retrospective cohort aged 18 years or older with continuous
      enrollment during the study period. Longitudinal multivariate cost analyses were
      performed using generalized estimating equations with demographic adjustments.
      RESULTS: The annual incremental mean costs of smoking by age group ranged from
      $1274 to $1401. The incremental costs of morbid obesity II by age group ranged
      from $5467 to $5530. These incremental costs drop substantially when
      comorbidities are included. CONCLUSIONS: Obesity and smoking have large long-term
      impacts on health care costs of working-age adults. Controlling comorbidities
      impacted incremental costs of obesity but may lead to underestimation of the true
      incremental costs because obesity is a risk factor for developing chronic
      conditions.

PMID- 22361993
TI  - The effect of participation in a Fitness Rewards Program on medical care
      expenditures in an employee population.
AB  - OBJECTIVE: In 2008, the University of Minnesota began offering the Fitness
      Rewards Program (FRP) that provides a monthly credit toward fitness center dues
      for individuals who exercise at a participating facility at least 8 times per
      month. This study evaluates whether participation in the FRP is associated with a
      decrease in medical spending. METHODS: Using a difference-in-differences
      approach, we estimate multivariate regression models of average monthly medical
      expenditures for 2006 through 2008. RESULTS: We find positive benefits from
      reduced medical spending among highly persistent FRP exercisers. However, the
      results are sensitive to the inclusion or exclusion of individuals who had very
      high medical expenditures in any year. CONCLUSIONS: Offering exercise-focused
      wellness initiatives may have economic benefits for employers, but further
      research is needed to understand the sensitivity of results to the inclusion of
      outliers.

PMID- 22361994
TI  - Predictors of the development of metabolic syndrome in male workers: a 3-year
      follow-up study.
AB  - BACKGROUND: Risk assessment for the development of metabolic syndrome (MetS) is
      an important strategy for prevention. METHODS: A 3-year follow-up study was
      conducted for 1677 Japanese workers not fulfilling the diagnostic criteria for
      MetS. Age and the five components of MetS, serum uric acid, serum insulin,
      lifestyle factors, and occupational position were used for the analysis. RESULTS:
      The odds ratios (95% confidence intervals) for MetS development among the
      subjects who initially had one or two MetS components were 3.1 (1.8 to 5.3) and
      7.8 (4.5 to 13.5), respectively. When the MetS components were used as
      independent variables, the odds ratios (95% confidence intervals) of each
      component were significant for MetS development. Occupational position did not
      present significance. CONCLUSION: Presence of each component of MetS as well as
      the number of MetS components are powerful predictors of the development of MetS
      after 3 years.

PMID- 22361995
TI  - Integration of metabolic and cardiovascular diurnal rhythms by circadian clock.
AB  - Understanding how the 24-hour blood-pressure rhythm is programmed has been one of
      the most challenging questions in cardiovascular research. The 24-hour blood
      pressure rhythm is primarily driven by the circadian clock system, in which the
      master circadian pacemaker within the suprachiasmatic nuclei of the hypothalamus
      is first entrained to the light/dark cycle and then transmits synchronizing
      signals to the peripheral clocks common to most tissues, including the heart and
      blood vessels. However, the circadian system is more complex than this basic
      hierarchical structure, as indicated by the discovery that peripheral clocks are
      either influenced to some degree or fully driven by temporal changes in energy
      homeostasis, independent of the light entrainment pathway. Through various
      comparative genomic approaches and through studies exploiting mouse genetics and
      transgenics, we now appreciate that cardiovascular tissues possess a large number
      of metabolic genes whose expression cycle and reciprocally affect the
      transcriptional control of major circadian clock genes. These findings indicate
      that metabolic cycles can directly or indirectly affect the diurnal rhythm of
      cardiovascular function. Here, we discuss a framework for understanding how the
      24-hour blood-pressure rhythm is driven by the circadian system that integrates
      cardiovascular and metabolic function.

PMID- 22361997
TI  - Chiroptical generation and inversion during the mirror-symmetry-breaking
      aggregation of dialkylpolysilanes due to limonene chirality.
AB  - We observed the emergence and inversion of chiroptical handedness in three
      chiroptically silent dialkylpolysilanes during aggregation in limonene-methanol
      THF tersolvents.

PMID- 22361996
TI  - Association of walking speed in late midlife with mortality: results from the
      Whitehall II cohort study.
AB  - Slow walking speed is associated with increased mortality in the elderly, but it
      is unknown whether a similar association is present in late midlife. Our aim was
      to examine walking speed in late midlife as a predictor of mortality, as well as
      factors that may explain this association. Data are drawn from the Whitehall II
      longitudinal cohort study of British civil servants. The analyses are based on
      6,266 participants (29% women; mean age = 61 years, SD = 6) for whom "walking
      speed at usual pace" was measured over 8 ft (2.44 m) at baseline. Participants
      were followed for all-cause and cause-specific mortalities during a mean of 6.4
      (SD = 0.8) years. During this period, 227 participants died. Participants in the
      bottom sex-specific third of walking speed (men, <1.26 m/s; women, <1.09 m/s) had
      an increased risk of death compared to those in the middle and top thirds (age-
      and sex-adjusted hazard ratio = 1.89, 95% confidence interval (CI) = 1.45-2.46),
      with no evidence of effect modification by age or sex (interactions, P >= 0.40).
      The association between walking speed and mortality was partially explained by
      baseline inflammatory markers (percentage reduction of the association 22.8%),
      height and body mass index (16.6%), chronic diseases (14.0%), and health
      behaviors (13.4%). Together these and other baseline factors (socioeconomic
      status, cardiovascular risk factors, cognitive function) explained 48.5% of the
      association (adjusted hazard ratio = 1.39, 95% CI = 1.04-1.84). In conclusion,
      walking speed measured in late midlife seems to be an important marker of
      mortality risk; multiple factors, in particular inflammatory markers, partially
      explain this association.

PMID- 22361999
TI  - Cost-utility of the 21-gene recurrence score assay in node-negative and node
      positive breast cancer.
AB  - The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinico
      pathologic prognostication and is predictive of adjuvant chemotherapy benefit in
      node-negative (N-) and node-positive (N+), endocrine-sensitive breast cancer. RS
      is a costly assay that is associated with good 'value for money' in N- disease,
      while economic evaluations in N+ disease based on most recent data have not been
      conducted. We examined the cost-utility (CU) of a RS-guided adjuvant strategy,
      compared to current practice without RS in N- and N+, endocrine-sensitive, breast
      cancer from a Canadian health care system perspective. A generic state-transition
      model was developed to compute cumulative costs and quality-adjusted life years
      (QALYs) over a 25-year horizon. Patient outcomes with and without chemotherapy in
      RS-untested cohorts and in those with low, intermediate and high RS were examined
      based on the reported prognostic and predictive impact of RS in N- and N+
      disease. Chemotherapy utilization (current vs. RS-guided), unit costs and
      utilities were derived from a Nova Scotia Canadian population-based cohort, local
      unit costs and the literature. Costs and outcomes were discounted at 3% annually,
      and costs were reported in 2011 Canadian dollars ($). Probabilistic and one-way
      sensitivity analyses were conducted for key model parameters. Compared to a non
      RS-guided strategy, RS-guided adjuvant therapy was associated with $2,585 and
      $864 incremental costs, 0.27 and 0.06 QALY gains, and resultant CUs of $9,591 and
      $14,844 per QALY gained for N- and N+ disease, respectively. CU estimates were
      robust to key model parameters, and were most sensitive to chemo utilization
      proportions. RS-guided adjuvant therapy appears to be a cost-effective strategy
      in both N- and N+, endocrine-sensitive breast cancer with resultant CU ratios
      well below commonly quoted thresholds.

PMID- 22361998
TI  - Bioactive glasses as carriers for bioactive molecules and therapeutic drugs: a
      review.
AB  - Bioactive glasses (BG) show great promise for bone tissue engineering based on
      their key properties, e.g., biocompatibility, biodegradability, osteoconductivity
      as well as osteogenic and angiogenic potential, which make them excellent
      candidates for bone tissue scaffolds and bone substitute materials. Recent work
      has shown that dissolution products of bioactive glasses have the potential to
      induce angiogenesis in addition to their known effect of influencing gene
      expression and promoting osteoblastic differentiation. One of the most
      interesting features of BG is their ability to bond both to soft and hard
      tissues, depending on their composition. To intensify the positive impact of BG
      for medical applications, there are considerable research efforts on using
      bioactive glass based platforms as carriers for the encapsulation, delivery and
      controlled release of bioactive molecules and therapeutic drugs. Different types
      of bioactive glasses have been considered in combination with different
      therapeutic drugs, hormones, growth factors and peptides. Using bioactive glasses
      as drug delivery system combines thus the effectiveness of therapeutic drugs (or
      bioactive/signaling molecules) with the intrinsic advantages of this inorganic
      biomaterial. Considering research carried out in the last 15 years, this review
      presents the different chemical compositions and morphologies of bioactive
      glasses used as carrier for bioactive molecules and therapeutic drugs and
      discusses the expanding potential of BG with drug delivery capability focusing in
      the field of bone tissue engineering.

PMID- 22362001
TI  - Generating co-management at Kasha Katuwe Tent Rocks National Monument, New
      Mexico.
AB  - Collaborative planning theory and co-management paradigms promise conflict
      prevention and the incorporation of indigenous knowledge into plans. Critics
      argue that without devolved power to culturally legitimate institutions,
      indigenous perspectives are marginalized. Co-management practice in North America
      is largely limited to treaty-protected fish and wildlife because federal agencies
      cannot devolve land management authority. This paper explores why the Pueblo de
      Cochiti, a federally recognized American Indian Tribe, and the U.S. Bureau of
      Land Management sustained an rare joint management agreement for the Kasha-Katuwe
      Tent Rocks National Monument in New Mexico despite a history of conflict over
      federal control of customary tribal lands that discouraged the Pueblo from
      working with federal agencies. Based on the participant interviews and documents,
      the case suggests that clear agreements, management attitudes, and the direct
      representation of indigenous forms of government helped achieve presumed co
      management benefits. However, parties enter these agreements strategically. We
      should study, not assume, participant goals in collaborative processes and co
      management institutions and pay special attention to the opportunities and
      constraints of federal laws and institutional culture for collaborative resource
      management with tribal and local communities.

PMID- 22362000
TI  - Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic
      lymphocytic leukemia B-cell activation and migration.
AB  - Syk is a protein tyrosine kinase that couples B-cell receptor (BCR) activation
      with downstream signaling pathways, affecting cell survival and proliferation.
      Moreover, Syk is involved in BCR-independent functions, such as B-cell migration
      and adhesion. In chronic lymphocytic leukemia (CLL), Syk becomes activated by
      external signals from the tissue microenvironment, and was targeted in a first
      clinical trial with R788 (fostamatinib), a relatively nonspecific Syk inhibitor.
      Here, we characterize the activity of two novel, highly selective Syk inhibitors,
      PRT318 and P505-15, in assays that model CLL interactions with the
      microenvironment. PRT318 and P505-15 effectively antagonize CLL cell survival
      after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit
      BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and
      leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and
      beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and
      extracellular signal-regulated kinase phosphorylation after BCR triggering. These
      findings demonstrate that the selective Syk inhibitors PRT318 and P505-15 are
      highly effective for inhibition of CLL survival and tissue homing circuits, and
      support the therapeutic development of these agents in patients with CLL, other B
      cell malignancies and autoimmune disorders.

PMID- 22362002
TI  - Systematic review and meta-analysis of outcomes following pathological complete
      response to neoadjuvant chemoradiotherapy for rectal cancer.
AB  - BACKGROUND: Following neoadjuvant chemoradiotherapy (CRT) and interval
      proctectomy, 15-20 per cent of patients are found to have a pathological complete
      response (pCR) to combined multimodal therapy, but controversy persists about
      whether this yields a survival benefit. This systematic review evaluated current
      evidence regarding long-term oncological outcomes in patients found to have a pCR
      to neoadjuvant CRT. METHODS: Three major databases (PubMed, MEDLINE and the
      Cochrane Library) were searched. The systematic review included all original
      articles reporting long-term outcomes in patients with rectal cancer who had a
      pCR to neoadjuvant CRT, published in English, from January 1950 to March 2011.
      RESULTS: A total of 724 studies were identified for screening. After applying
      inclusion and exclusion criteria, 16 studies involving 3363 patients (1263 with
      pCR and 2100 without) were included (mean age 60 years, 65.0 per cent men). Some
      73.4 per cent had a sphincter-saving procedure. Mean follow-up was 55.5 (range 40
      87) months. For patients with a pCR, the weighted mean local recurrence rate was
      0.7 (range 0-2.6) per cent. Distant failure was observed in 8.7 per cent. Five
      year overall and disease-free survival rates were 90.2 and 87.0 per cent
      respectively. Compared with non-responders, a pCR was associated with fewer local
      recurrences (odds ratio (OR) 0.25; P = 0.002) and less frequent distant failure
      (OR 0.23; P < 0.001), with a greater likelihood of being alive (OR 3.28; P =
      0.001) and disease-free (OR 4.33, P < 0.001) at 5 years. CONCLUSION: A pCR
      following neoadjuvant CRT is associated with excellent long-term survival, with
      low rates of local recurrence and distant failure.

PMID- 22362003
TI  - Inhibition of corneal neovascularization in rats by systemic administration of
      sorafenib.
AB  - PURPOSE: To evaluate the effect of orally administered sorafenib on corneal
      neovascularization in rat models. METHODS: In male Sprague-Dawley rats, a silver
      nitrate applicator was placed on the central cornea in both eyes to elicit
      angiogenesis. Rats were divided into 3 groups, the control group and the 2
      sorafenib-treated groups (low dose, 30 mg . kg(-1) . day(-1); high dose, 60 mg .
      kg(-1) . day(-1)). The area of corneal neovascularization was measured by image
      analysis. Vascular endothelial growth factor receptor 2 (VEGFR2) messenger RNA
      expression was measured in rat corneas by reverse transcription-polymerase chain
      reaction, and the expression of phosphorylated extracellular signal-regulated
      kinase (ERK) was measured by Western blot analysis 1 week after cauterization.
      RESULTS: The area of corneal neovascularization was significantly reduced by 44%
      in the 30 mg . kg(-1) . day(-1) group and by 66% in the 60 mg . kg(-1) . day(-1)
      group, compared with the control group (P = 0.014 and P < 0.0001). Corneal VEGFR2
      messenger RNA expression was higher in the control group than in the sorafenib
      treated groups. The expression of phosphorylated ERK in rat corneas was
      suppressed in the sorafenib-treated groups but not in the control group.
      CONCLUSIONS: Oral administration of a multikinase inhibitor (sorafenib)
      significantly reduced the development of experimental corneal neovascularization
      in a dose-dependent manner. This inhibitory effect is probably related to the
      suppression of ERK phosphorylation by sorafenib.

PMID- 22362004
TI  - Antimicrobial susceptibility of nontuberculous mycobacteria from eye infections.
AB  - PURPOSE: To characterize formerly designated atypical or nontuberculous
      mycobacteria (NTM) associated with eye infections. METHODS: All clinical NTM eye
      isolates (112 isolates from 100 patients) submitted to a single national NTM
      reference laboratory between 1982 and 2009 were identified using polymerase chain
      reaction and restriction fragment length polymorphism of the hsp65 gene. Isolates
      were tested against 10 antimicrobials, including besifloxacin, a new 8-chloro
      fluoroquinolone. Assessments included species of NTM recovered, year of
      isolation, type of eye infection, geographic location, and drug susceptibilities.
      RESULTS: In the 1980s, the major pathogen isolated was Mycobacterium abscessus.
      In the 1990 s, Mycobacterium chelonae emerged as the major pathogen. By 2000, it
      was responsible for more than 50% of all cases. The majority of M. abscessus and
      Mycobacterium fortuitum were from southern coastal states and Texas, whereas M.
      chelonae isolates were more widespread geographically. The most active
      antimicrobials were amikacin and clarithromycin/azithromycin for M. abscessus and
      clarithromycin/azithromycin, amikacin, and tobramycin, and the quinolones for M.
      chelonae. CONCLUSIONS: This is the largest study of NTM ophthalmic isolates to
      date and is the first to include susceptibilities and molecular identification
      for all isolates studied. This series establishes M. chelonae (44%) and M.
      abscessus (37%) as the NTM species most frequently associated with ophthalmic
      infections. Topical ophthalmic fluoroquinolones may have a role in the management
      of ocular infections involving M. chelonae and M. fortuitum.

PMID- 22362005
TI  - Angioregressive pretreatment of mature corneal blood vessels before keratoplasty:
      fine-needle vessel coagulation combined with anti-VEGFs.
AB  - PURPOSE: To evaluate the efficacy and safety of combined feeder vessel
      coagulation and topical antiangiogenic therapy using bevacizumab in the treatment
      of mature corneal blood vessels. METHODS: Sixteen eyes of 16 patients with mature
      corneal neovascularization (NV) due to different underlying corneal diseases
      underwent fine-needle feeder vessel coagulation by diathermy and were treated
      postoperatively for up to 4 weeks with topical bevacizumab eye drops (containing
      5 mg/mL bevacizumab) 5 times a day. Nine patients received an additional
      subconjunctival bevacizumab injection at the time of cautery. RESULTS: The mean
      duration of follow-up was 276 +/- 147.3 days (range, 29-464 days). Regression of
      the feeder vessel was observed in 14 eyes. The vascularized area was reduced
      significantly (P < 0.05). Combined subconjunctival and eye drop antivascular
      endothelial growth factor treatment was significantly more effective in reducing
      the vascularized area compared with antivascular endothelial growth factor eye
      drop therapy alone (P < 0.05). Five patients (5 eyes) needed a second treatment.
      Thirteen patients (13 eyes) receiving topical bevacizumab treatment combined with
      feeder vessel coagulation showed stable visual acuity. Two patients had improved
      visual acuity. One patient had enlarged area of lipid keratopathy despite
      successful treatment of corneal NV and thus decreased visual acuity. Overall,
      there was a nonsignificant improvement of best-corrected visual acuity (P >
      0.05). CONCLUSIONS: In this pilot study, fine-needle feeder vessel coagulation
      combined with topical bevacizumab application for treatment of mature corneal NV
      seemed to be a well-tolerated new treatment option to regress corneal NV. This
      may not only improve corneal transparency but also "preconditions" such a cornea
      for future keratoplasty.

PMID- 22362007
TI  - Accuracy of perceptual and acoustic methods for the detection of inspiratory loci
      in spontaneous speech.
AB  - The present study investigates the accuracy of perceptually and acoustically
      determined inspiratory loci in spontaneous speech for the purpose of identifying
      breath groups. Sixteen participants were asked to talk about simple topics in
      daily life at a comfortable speaking rate and loudness while connected to a
      pneumotach and audio microphone. The locations of inspiratory loci were
      determined on the basis of the aerodynamic signal, which served as a reference
      for loci identified perceptually and acoustically. Signal detection theory was
      used to evaluate the accuracy of the methods. The results showed that the
      greatest accuracy in pause detection was achieved (1) perceptually, on the basis
      of agreement between at least two of three judges, and (2) acoustically, using a
      pause duration threshold of 300 ms. In general, the perceptually based method was
      more accurate than was the acoustically based method. Inconsistencies among
      perceptually determined, acoustically determined, and aerodynamically determined
      inspiratory loci for spontaneous speech should be weighed in selecting a method
      of breath group determination.

PMID- 22362008
TI  - Bendamustine: mechanism of action and clinical data.
AB  - Bendamustine is a chemotherapeutic agent that displays a unique pattern of
      cytotoxicity compared with conventional alkylating agents. Bendamustine was
      originally synthesized in the former East German Democratic Republic in the
      1960s. It was designed to have both alkylating and antimetabolite properties. The
      alkylating agent properties are similar to those seen with cyclophosphamide,
      chlorambucil, and melphalan, and the benzimidazole ring is similar to cladribine.
      Molecular analyses have revealed that bendamustine differs from other alkylating
      agents in its mechanism of action. Differences have been observed in regard to
      its effects on DNA repair and cell cycle progression. Moreover, bendamustine can
      induce cell death through both apoptotic and nonapoptotic pathways, thereby
      retaining activity even in cells without a functional apoptotic pathway.
      Bendamustine has demonstrated significant efficacy in patients with indolent
      lymphomas and chronic lymphocytic leukemia (CLL), including in patients with
      disease refractory to conventional alkylating agents and rituximab. The toxicity
      profile of bendamustine is also superior to that of conventional alkylating
      agents. Combination therapy with bendamustine and rituximab has demonstrated
      superior efficacy to a standard rituximab-containing chemotherapy regimen in
      patients with previously untreated indolent B-cell non-Hodgkin lymphoma, and it
      is currently being compared against the standard first-line regimen in CLL:
      fludarabine, cyclophosphamide, and rituximab. Ongoing and planned studies are
      evaluating new strategies in which bendamustine is being combined with existing
      agents and with novel therapies to optimize use in different clinical settings.

PMID- 22362009
TI  - Features of Japanese patients with myelodysplastic syndrome in an aging
      population of Sado Island.
AB  - Myelodysplastic syndrome (MDS) is relatively common in the elderly, and aging of
      populations is progressing in developed nations, notably so in Japan. The major
      age group in Japan and Sado Island are distributed between 30 and 60 and between
      50 and 80, respectively. The aim of this study was to analyze the features of MDS
      in the population of Sado Island to anticipate the characteristics of the disease
      in the near future. One-hundred and fifty-three patients (71 male, 82 female, 19
      94 years old, median 73 years old) with de novo MDS between 1985 and 2005 were
      retrospectively evaluated. All patients were reclassified according to WHO-2001
      criteria. The predictive power of the international prognostic scoring system and
      the WHO classification-based prognostic scoring system were evaluated. The major
      causes of death were leukemic transformation (38%) in refractory anemia with an
      excess of blasts and infection (48%) for total MDS. Age was another independent
      prognostic factor. Elderly patients exhibited a significantly poorer prognosis
      mainly due to infections such as pneumonia. Although novel remedies for MDS and
      hyperferremia have recently been developed, prevention of infection remains
      important in MDS, particularly for older patients.

PMID- 22362010
TI  - [Malaria in Gabon: results of a clinical and laboratory study at the Chinese
      Gabonese Friendship Hospital of Franceville].
AB  - Despite progress in the control of malaria, it remains a serious public health
      problem. Substantial declines in malaria transmission, morbidity and mortality
      have nonetheless been reported in several countries where new malaria control
      strategies have been implemented. We conducted this molecular and epidemiological
      analysis of malaria in the pediatric department of the Chinese-Gabon Friendship
      Hospital (HCGC) in Franceville in 2010. Franceville is the third largest town in
      Gabon, and malaria transmission is high year-round. We included 945 children, 756
      of them febrile. Malaria was diagnosed based on the detection of P. falciparum in
      thick blood films, with Lambarene's method. Malaria prevalence among the febrile
      children included in this study was 17.9% (n=135). The burden of malaria is thus
      lower than in the past; it is now the second leading cause of pediatric hospital
      visits, rather than the leading cause as it was in 2004. The children's mean age
      was 48.5 +/- 3.9 months, older than in 2004 (p<0.05). We also analysed the
      molecular drug resistance marker, Pfmdr1. The prevalence of the wild-type
      genotype N86 of Pfmdr1 was 47.4% (n=64), higher than in 2004 (p<0.001). The
      increased prevalence of codon 1246 was not significant. Socio-economic factors
      and known malaria risk factors were analysed. We found that the use of
      Insecticide-treated mosquito nets and the provision of information (education or
      communication) to parents and guardians about malaria were protective factors
      against the disease. In conclusion, a larger study of the entire region over a
      longer period is necessary to characterise malaria in Franceville today.
      Transmission factors must also be studied.

PMID- 22362011
TI  - Lead in potable water sources in Abakaliki metropolis, South-East, Nigeria.
AB  - Lead concentration was analyzed in potable water samples (25 well water, 15
      borehole water, 7 tap water and 3 stream/river water samples), collected randomly
      from 5 zones (Abakaliki urban, Azuiyiokwu, Kpirikpiri, Nkaliki and Onuebonyi/rice
      mill) in Abakaliki metropolis, South-East Nigeria, using Atomic absorption
      spectrophotometry. The mean +/- SD lead levels of Tap, well, borehole and
      stream/river water were 0.13 +/- 0.08, 1.04 +/- 0.19, 0.78 +/- 0.19 and 0.83 +/-
      0.22 mg/L, respectively. There was statistically significant difference (p =
      0.016) in lead concentrations in well water, compared with tap water. The highest
      well water lead level was found in Azuiyiokwu whereas the highest level in
      borehole water was in Abakaliki urban.

PMID- 22362013
TI  - Standardisation in standards.

PMID- 22362012
TI  - Short- and mid-term repeatability of macular pigment optical density measurements
      using spectral fundus reflectance.
AB  - BACKGROUND: Several methods have been proposed for measuring macular pigment
      optical density (MPOD). To date, none of the realized techniques can be
      considered as "gold standard". A key issue for the clinical applicability of a
      method is its repeatability. In this study, we investigated short- and mid-term
      repeatability of MPOD measurements using reflectometry. METHODS: A total of 12
      healthy young subjects were measured 5 times on 5 consecutive days. Repeatability
      over 6 months was investigated in patients with AMD. The data in AMD patients
      were taken from a recently published placebo controlled study investigating the
      effect of lutein supplementation on MPOD (n = 37; [1]). Four measurements over 6
      months were used to calculate repeatability. Spectral fundus reflectance of the
      fovea was measured in a 2.3 degrees  detection field with a custom-built fundus
      reflectometer. Calculation of MPOD was based on a previously published fundus
      reflectance model. RESULTS: The coefficients of variation were 6.2 +/- 2.4% and
      8.0 +/- 5.5% in the healthy and AMD group, respectively. Bland-Altman plots
      indicate that the difference between measurements at day 1 and day 5 in healthy
      subjects and day 1 and month 6 in AMD patients was small. The maximum deviation
      in MPOD in a healthy subject was 0.07 (22.6%), and 0.17 (51.5%) in a patient with
      AMD. CONCLUSIONS: Reflectometry provides adequate short-term and mid-term
      repeatability for measuring MPOD. Accordingly, the technique makes it possible to
      monitor MPOD in patients with AMD and to study the influence of supplementation
      in these subjects. In addition, the variability of the technique is small enough
      to allow for clinical trials with reasonable sample size.

PMID- 22362014
TI  - Effects of exposure to low-level lead on spatial learning and memory and the
      expression of mGluR1, NMDA receptor in different developmental stages of rats.
AB  - The effect of different periods of lead exposure on deficits of learning and
      memory is still unclear. In this study, we conduct in vivo experiment to
      investigate the critical stages when lead induced neurotoxicity in rats and its
      underlying mechanisms in some critical stages. Rats were exposed to 0.2% mg/ml
      lead acetate solution via drinking water during gestation, lactation and
      ablactation periods. Behavior deficits were found in gestation and lactation. N
      Methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) increased during gestation
      both in hippocampus and cerebral cortex compared to the control group; in all
      treatment groups NR2B decreased in hippocampus and in cerebral cortex during the
      lactation period. Meanwhile, in hippocampus metabotropic glutamate receptor 1
      (mGluR1) decreased during gestation and lactation periods but increased during
      the ablactation period. These observations suggest that exposure to lead in
      gestation and lactation periods could cause neurobehavioral deficits which extend
      to adulthood, and lactation was a more sensitive period for lead exposure.
      Furthermore, the abnormal expression of NMDA receptor 2 (NMDAR 2) subunits and
      mGluR1 are likely to be associated with the impairment. 

PMID- 22362015
TI  - Determination of the genotoxic effects of Convolvulus arvensis extracts on corn
      (Zea mays L.) seeds.
AB  - In this research, the methanolic extracts of Convolvulus arvensis were tested for
      genotoxic and inhibitor activity on the total soluble protein content and the
      genomic template stability against corn Zea mays L. seed. The methanol extracts
      of leaf, stem and root of C. arvensis were diluted to 50, 75 and 100 MUl
      concentrations and applied to corn seed. The total soluble protein and genomic
      template stability results were compared with the control. The results showed
      that especially 100 MUl extracts of diluted leaf, stem and root had a strong
      inhibitory activity on the genomic template stability. The changes occurred in
      random amplification of polymorphic DNA (RAPD) profiles of C. arvensis extract
      treatment included variation in band intensity, loss of bands and appearance of
      new bands compared with control. Also, the results obtained from this study
      revealed that the increase in the concentrations of C. arvensis extract increased
      the total soluble protein content in maize. The results suggested that RAPD
      analysis and total protein analysis could be applied as a suitable biomarker
      assay for the detection of genotoxic effects of plant allelochemicals.

PMID- 22362016
TI  - Effect of levosimendan injection on oxidative stress of rat myocardium.
AB  - This experiment was designed to investigate the effect of levosimendan injection
      on lipid peroxidation product malondialdehyde (MDA) and antioxidant glutathione
      (GSH) levels, and activities of antioxidant enzymes in myocardium of rats. Twenty
      male Wistar-albino rats were divided randomly into 2 study groups, each
      consisting of 10 rats. The animals in the first group were not treated with drug
      and served as control. It was found that the MDA and GSH levels decreased in
      levosimendan injected group. Superoxide dismutase, glutathione peroxidase,
      catalase and carbonic anhydrase enzyme activities were lower in levosimendan
      injected group than controls. It was concluded that lower tissue free radical
      level caused by levosimendan injection led to a lower antioxidant enzymes
      synthesis in the body and a decrease in the antioxidant enzyme activity and free
      radical scavenger level in myocardium of rat.

PMID- 22362017
TI  - DPPH free radical scavenging activity and phenotypic difference in
      hepatoprotective plant (Silybum marianum L.).
AB  - Silybum marianum L. is medicinally important for its active principle component
      silymarin. Silymarin regenerates damaged hepatic tissues. On the basis of such
      regenerative properties, the radical scavenging activity (1,1-diphenyl-2
      picrylhydrazyl (DPPH)) of different tissues and the phenotypic difference of the
      hepatoprotective species, S. marianum L. were evaluated. There was less
      phenotypic difference in purple and white varieties of S. marianum. Assay of the
      antioxidant potential of different parts of the plant revealed that significantly
      higher activity (78.2%) was observed in seeds of the purple flowering plant than
      seeds of white flowering plant (49%) after different time intervals. Young leaves
      collected from white flowering plant exhibit 64.8% activity, which is higher than
      the purple flowering plant (55.1%). Significantly, same activity was observed in
      mature leaves of white (52%) and purple flowering plants (50%). The main stem
      collected from both the varieties exhibits similar activity from 50 to 52%. A
      67.2% activity was recorded for mature roots of white flowering plant followed by
      roots of the purple variety (65%). The present study revealed that seeds and
      roots of both the varieties scavenge and detoxify more DPPH free radicals than
      other plant parts and can be used as a source of natural antioxidants and food
      additives.

PMID- 22362018
TI  - Steering the enzymatic activity of proteins by ionic liquids. A case study of the
      enzyme kinetics of yeast alcohol dehydrogenase.
AB  - We explore ion-specific effects exerted by ionic liquids (ILs) on the enzyme
      kinetics of yeast alcohol dehydrogenase. The Michaelis-Menten reaction scheme is
      used to parameterize the observed kinetics in terms of the apparent dissociation
      constant of the substrate (Michaelis-Menten constant) K(M), the turnover number
      k(cat), which reflects the number of product molecules per enzyme molecule per
      second, and the enzymatic efficiency k(cat)/K(M) of the reaction. Results for
      fifteen salts are used to deduce Hofmeister anion and cation series. The ion
      rankings derived from K(M), k(cat) and k(cat)/K(M) differ markedly. Only the
      results for the enzymatic efficiency correspond to expectations from other
      phenomena, such as the thermal stability of native proteins. Anion variation has
      a significantly larger effect on the enzymatic efficiency than cation variation.
      All ILs decrease k(cat) relative to its value for the IL-free solution, thus
      driving enzyme deactivation. Enhancements of the enzymatic efficiency by some
      ions are founded in their effects on the Michaelis-Menten constant. The observed
      Hofmeister anion and cation series point toward hydrophobic interactions as an
      important factor controlling ion-specific effects on the enzymatic activity.

PMID- 22362019
TI  - The ring-chain tautomeric equilibria of selenium macrocyclic compounds: the
      isolation of the ring tautomer.
AB  - A broadening of the investigation of the ring-chain tautomeric process of N
      substituted 1,3-X,N-heterocycles (X = O, S, NR) to Se containing macrocyclic
      compounds allowed the isolation and structurally solid state characterization of
      the cyclic tautomer 7, which due to the length of the aliphatic chain, is able to
      form a stable six-membered ring (6-endo-trig). The theoretical calculations based
      on the DFT method (Gaussian 03 software package) also support the fact that
      tautomer 7 is more stable than the chain tautomer 6. Thus, based on the ring
      chain tautomerism of the macrocycles that contain alkyl chains with amino-imino,
      imino-alcohol or sulphur-imino groups, combined with a strategy that allows the
      formation of a stable six-membered ring, the main reaction products will be the
      cyclic tautomers. The ring-chain equilibria of these macrocycles could be
      exploited advantageously in different areas of macrocyclic, physical and
      medicinal chemistry in order to obtain compounds with practical applications.

PMID- 22362020
TI  - Immunogold labeling-induced synergy effect for amplified photoelectrochemical
      immunoassay of prostate-specific antigen.
AB  - A new photoelectrochemical immunoassay for prostate-specific antigen (PSA) was
      successfully developed with high sensitivity via immunogold labeling.

PMID- 22362021
TI  - Acoustofluidics 8: applications of acoustophoresis in continuous flow
      microsystems.
AB  - This acoustofluidics tutorial focuses on continuous flow-based half wavelength
      resonator systems operated in the transversal mode, where the direction of the
      primary acoustic force acts in plane with the microchip. The transversal
      actuation mode facilitates integration with up- and downstream microchannel
      networks as well as visual control of the acoustic focusing experiment.
      Applications of particle enrichment in an acoustic half wavelength resonator are
      discussed as well as clarification of the carrier fluid from undesired particles.
      Binary separation of particle/vesicle/cell mixtures into two subpopulations is
      outlined based on the different polarities of the acoustic contrast factor.
      Furthermore, continuous flow separation of different particle/cell types is
      described where both Free Flow Acoustophoresis (FFA) and binary acoustophoresis
      are utilized. By capitalizing on the laminar flow regime, acoustophoresis has
      proven especially successful in performing bead/cell translations between
      different buffer systems. Likewise, the ability to controllably translate
      particulate matter across streamlines has opened a route to valving of
      cells/particles without any moving parts, where event triggered cell sorting is
      becoming an increasing area of activity. Recent developments now also enable
      measurements of fundamental cell properties such as density and compressibility
      by means of acoustophoresis. General aspects on working with live cells in
      acoustophoresis systems are discussed as well as available means to quantify the
      outcome of cell and particle separation experiments performed by acoustophoresis.

PMID- 22362022
TI  - A new access to 3-substituted-1(2H)-isoquinolone by tandem palladium-catalyzed
      intramolecular aminocarbonylation annulation.
AB  - An original tribromide derivative based, palladium-catalyzed synthesis of 3
      substituted-1(2H)-isoquinolone is described based on a regioselective Suzuki
      Miyaura C-C coupling on o-halo-(2,2-dihalovinyl)-benzene followed by a palladium
      catalyzed amination-carbonylation-cyclization reaction. This sequence efficiently
      proceeds to build up isoquinolone in fair to good yields over a one-pot 3-bond
      synthesis reaction.

PMID- 22362023
TI  - Acoustic breath-phase detection using tracheal breath sounds.
AB  - Current breathing flow estimation methods use tracheal breath sounds, but one
      step of the process, 'breath phase (inspiration/expiration) detection', is done
      by either assuming alternating breath phases or using a second acoustic channel
      of lung sounds. The alternating assumption is unreliable for long recordings, non
      breathing events, such as apnea, swallow or cough change the alternating nature
      of the phases. Using lung sounds intensity requires the addition of a secondary
      channel and the associated labor. Hence, an automatic and accurate method for
      breath-phase detection using only tracheal sounds would be of great benefit. We
      present a method using several breath sound parameters to differentiate between
      the two respiratory phases. The proposed method is novel and independent of flow
      level; it requires only one prior- and one post-breath sound segment to identify
      the phase. The proposed method was tested on data from 93 healthy individuals,
      without any history of pulmonary diseases breathing at 4 different flow levels.
      The most prominent features were from the duration, volume and shape of the sound
      envelope. This method has shown an accuracy of 95.6% with 95.5% sensitivity and
      95.6% specificity for breath-phase identification without assuming breath-phase
      alteration and/or using any other information.

PMID- 22362024
TI  - The theory of velocity selective neural recording: a study based on simulation.
AB  - This paper describes the improvements to the theory of velocity selective
      recording and some simulation results. In this method, activity in different
      groups of axons is discriminated by their propagation velocity. A multi-electrode
      cuff and an array of amplifiers produce multiple neural signals; if artificial
      delays are inserted and the signals are added, the activity in axons of the
      matched velocity are emphasized. We call this intrinsic velocity selective
      recording. However, simulation shows that interpreting the time signals is then
      not straight-forward and the selectivity Q(v) is low. New theory shows that
      bandpass filters improve the selectivity and explains why this is true in the
      time domain. A simulation study investigates the limits on the available velocity
      selectivity both with and without additive noise and with reasonable sampling
      rates and analogue-to-digital conversion parameters. Bandpass filters can improve
      the selectivity by factors up to 7 but this depends on the speed of the action
      potential and the signal-to-noise ratio.

PMID- 22362025
TI  - Fabrication and electromechanical characterization of near-field electrospun
      composite fibers.
AB  - We report the use of near-field electrospinning (NFES) as a route to fabricate
      composite electrodes. Electrodes made of composite fibers of multi-walled carbon
      nanotubes in polyethylene oxide (PEO) are formed via liquid deposition, with
      precise control over their configuration. The electromechanical properties of
      free-standing fibers and fibers deposited on elastic substrates are studied in
      detail. In particular, we examine the elastic deformation limit of the resulting
      free-standing fibers and find, similarly to bulk PEO composites, that the plastic
      deformation onset is below 2% of tensile strain. In comparison, the apparent
      deformation limit is much improved when the fibers are integrated onto a
      stretchable, elastic substrate. It is hoped that the NFES fabrication protocol
      presented here can provide a platform to direct-write polymeric electrodes, and
      to integrate both stiff and soft electrodes onto a variety of polymeric
      substrates.

PMID- 22362027
TI  - Positive selection for gains of N-linked glycosylation sites in hemagglutinin
      during evolution of H3N2 human influenza A virus.
AB  - The number of N-linked glycosylation sites in the globular head of hemagglutinin
      (HA) has increased during evolution of H3N2 human influenza A virus. Here natural
      selection operating on the gains of N-linked glycosylation sites was examined by
      using the single-site analysis and the single-substitution analysis. In the
      single-site analysis, positive selection was not inferred at the amino acid sites
      where the substitutions generating N-linked glycosylation sites were observed,
      but was detected at antigenic sites. In contrast, in the single-substitution
      analysis, positive selection was detected for the amino acid substitutions
      generating N-linked glycosylation sites. The single-site analysis and the single
      substitution analysis appeared to be suitable for detecting recurrent and
      episodic natural selection, respectively. The gains of N-linked glycosylation
      sites were likely to be positively selected for the function of shielding
      antigenic sites from immune responses. At the antigenic sites, positive selection
      appeared to have operated not only on the radical substitution but also on the
      conservative substitution in terms of the charge of amino acids, suggesting that
      the antigenic drift is not a by-product of the evolution of receptor binding
      avidity in HA of human H3N2 virus.

PMID- 22362028
TI  - Abnormal morphology of Bacillus subtilis ugtP mutant cells lacking glucolipids.
AB  - Bacillus subtilis Marburg 168 cells with disrupted ugtP, which encodes UDP
      glucosyltransferase involved in glucolipid synthesis, were bent and distended. In
      the ugtP mutant cells, the extracytoplasmic function sigmas SigM, SigV and SigX,
      were found to be activated. Introduction of a disrupted allele of sigM into the
      ugtP strain caused even more abnormal morphology, with cells taking on a balloon
      like shape; growth of these cells in LB medium was hampered by addition of 1.5%
      NaCl. Addition of MgSO4 or MnCl2 suppressed the abnormal morphology. In ugtP
      mutant cells the transcription of the mreB operon from an upstream promoter in
      maf (designated Pupstream mreB) and PmreBH was 4.3- and 2.3-fold higher,
      respectively, and localization of GFP-MreB was not in discrete dots (in an
      apparently helical pattern), but faint and in irregular clusters. GFP-MreB
      protein was reduced in the ugtP mutant cells. We suggest that glucolipids are
      important for MreB isoforms to take on the configuration that appears as discrete
      dots and plays a role in shaping cells into straight rods.

PMID- 22362030
TI  - Nucleotide sequence variation in mitochondrial COI gene among 147 silkworm
      (Bombyx mori) strains from Japanese, Chinese, European and moltinism classes.
AB  - We characterized the nucleotide sequences of PCR-amplified mitochondrial COI
      fragments of 147 silkworm (Bombyx mori) strains that have been maintained in the
      National Institute of Agrobiological Sciences. Coding sequences (714 bp) of the
      147 COI fragments were classified into eight haplotypes based on nucleotide
      differences at eight segregating sites. No length variation was identified in
      this region. The 5'-noncoding region showed different features, wherein changes
      in the number of Ts in the T-stretch, together with two base substitutions, were
      observed. As a result, the 147 COI noncoding sequences were classified into six
      haplotypes. Combining the coding and noncoding regions, we identified 14
      haplotypes. One of the 14 haplotypes, Hap1A was exclusively abundant in the
      Japanese native strain class, while this haplotype was less frequent in the other
      three native strain classes. This finding suggests that the Japanese strain class
      underwent significant genetic differentiation from the Chinese, European, and
      moltinism classes, when the each class is regarded as a population. Comparison of
      the nucleotide sequences to those of B. mandarina (which inhabits Japan) revealed
      changes that are significantly larger than those within either B. mori or B.
      mandarina. Furthermore, we detected no common haplotypes between them, which
      suggests the concept of suppressed gene flow between the two species.

PMID- 22362029
TI  - Fub1p, a novel protein isolated by boundary screening, binds the proteasome
      complex.
AB  - Silenced chromatin domains are restricted to specific regions. Eukaryotic
      chromosomes are organized into discrete domains delimited by domain boundaries.
      From approximately 6,000 genes in Saccharomyces cerevisiae, we previously
      isolated 55 boundary genes. In this study, we focus on the molecular function of
      one of boundary genes, YCR076C/FUB1 (function of boundary), whose function has
      not been clearly defined in vivo. Biochemical analysis of Fub1p revealed that it
      interacted with multiple subunits of the 20S proteasome core particle (20S CP).
      To further clarify the functional link between Fub1p and proteasome, several
      proteasome mutants were analyzed. Although only 20S CP subunits were isolated as
      Fub1p interactors, a genetic interaction was also observed for component of 19S
      regulatory particle (19S RP) suggesting involvement of Fub1p with the whole
      proteasome. We also analyzed the mechanism of boundary establishment by using
      proteasome composition factor-deficient strains. Deletion of pre9 and ump1, whose
      products have effects on the 20S CP, resulted in a decrease in boundary function.
      Domain analyses of Fub1p identified a minimum functional domain in the C terminus
      that was essential for boundary establishment and showed a limited sequence
      homology to the human PSMF1, which is known to inhibit proteasome activity.
      Finally, boundary assay showed that human PSMF1 also exhibited boundary
      establishment activity in yeast. Our results defined the functional correlation
      between Fub1p and PSMF1.

PMID- 22362031
TI  - Population genetic structure of the striped silverside, Atherinomorus
      endrachtensis (Atherinidae, Atheriniformes, Teleostei), inhabiting marine lakes
      and adjacent lagoons in Palau: marine lakes are "Islands" for marine species.
AB  - Although evidence for the evolution of terrestrial species on islands continues
      to rapidly accumulate, little is known about the evolution of marine species in
      geographically isolated environments such as islands as ocean currents often
      facilitate gene flow among populations. In this study, we focused on marine lakes
      of the Palau Islands, which are considered to be true analogues of terrestrial
      islands for marine species. To examine evolutionary processes in marine lakes, we
      conducted population genetic analyses on marine lake and lagoon populations of
      the striped silverside, Atherinomorus endrachtensis, using two mitochondrial DNA
      markers differing in evolutionary rate, the cytochrome b gene and the control
      region. The analyses revealed that the amount of genetic diversity of marine lake
      populations is much lower than that of lagoon populations and high levels of
      genetic differentiation occur among marine lake and lagoon populations. The
      present study has shown that marine lake populations have been completely
      isolated and have differentiated from lagoon populations, and each marine lake
      population is experiencing different evolutionary processes. These findings
      clearly demonstrate that marine lakes are excellent environments for the
      evolutionary study of marine species.

PMID- 22362032
TI  - Low genetic differentiation between two geographically separated populations of
      demersal gadiform fishes in the Southern Hemisphere.
AB  - The distribution patterns of many fishes between the three continents (Africa,
      Australia, and South America) in the Southern Hemisphere have been uncovered to
      be influenced by mostly vicariance or historical dispersal. Although some
      demersal fishes with intercontinental distribution are suggested to be more
      influenced by current/recent dispersal, few genetic studies have been made for
      demersal fishes so far. To provide more information for such fishes, genetic
      divergence was analyzed for two pairs of gadiform species and subspecies
      distributed around Australasia and South America: the blue grenadier, Macruronus
      novaezelandiae (from New Zealand) and the Patagonian grenadier, M. magellanicus
      (from South America) as well as two subspecies of the southern blue whiting,
      Micromesistius australis pallidus (from New Zealand) and M. a. australis (from
      South America). The sequence analyses of two mitochondrial DNA regions showed no
      divergence between Australasian and South American populations of the grenadiers
      and the southern blue whiting. The microsatellite DNA analysis also indicated
      significant but very minimal genetic differentiation between the two geographic
      populations of each pair. These results imply rather recent separation of the two
      geographic populations. Current/recent dispersal may be an important common
      factor for determining the distribution of demersal fishes in the Southern
      Hemisphere. Nonetheless, low but significant genetic differentiation observed
      requires treating the two populations of the economically important grenadiers
      and southern blue whiting, respectively, as different stocks for proper resource
      management.

PMID- 22362034
TI  - New frontiers and treatment paradigms for metastatic breast cancer. A Review of
      an adjunct symposium of the 2011 American Society of Clinical Oncology Annual
      Meeting, June 4, 2011 Chicago, Illinois.

PMID- 22362033
TI  - Analysis of canine transmissible veneral tumor genotypes using the D-loop region
      of mitochondrial DNA.
AB  - Canine transmissible venereal tumor (CTVT) is the only neoplasm that can be
      spread among dogs through cell transplantation. Therefore, this tumor does not
      originate from host cell transformation. Although CTVT has a monophyletic origin,
      several studies have shown the presence of genetic diversity which was probably
      acquired after the development of its original clone. To investigate the genetic
      diversity of CTVT in Mexico and its relation with CTVTs disseminated worldwide,
      we sequenced a fragment of mitochondrial DNA in 50 tumor samples and matched
      blood samples from dog hosts from Mexico. We found ten new haplotypes in tumor
      samples, which were all distinct from their matched host. The TVT1 haplotype was
      the most frequent in our samples, suggesting that it could be the origin of the
      others. We found that haplotypes in Mexico and other countries are distributed in
      two well-defined clusters. Our data also suggest a close relationship among
      American haplotypes (Mexico, USA, Chile and Brazil). Interestingly, these
      American haplotypes were also closely related to Asian haplotypes. Taking into
      account the estimated timing of the origin of CTVT, we propose that CTVT might
      have originated in Asia; consequently, haplotypes currently present in America
      could descend from Asiatic lineages.

PMID- 22362035
TI  - Randomized comparison of self-fixating and sutured mesh in open inguinal hernia
      repair.
AB  - BACKGROUND: Chronic groin pain after mesh repair of inguinal hernia has been
      attributed to the presence of sutures. METHODS: This randomized clinical trial
      compared inguinal hernia repair using a self-fixating composite mesh or a sutured
      lightweight mesh, with pain at 1 year as primary outcome. Patients completed a
      self-evaluation questionnaire at 2 weeks and were examined after 1 year. RESULTS:
      Some 198 patients received self-fixating mesh and 196 sutured mesh. There were no
      differences between the groups in mean pain scores measured on a visual analogue
      scale during 2 weeks of immediate convalescence or at 1 year. Chronic pain and
      discomfort was experienced by 36.3 per cent of patients in the self-fixating and
      34.1 per cent in the sutured mesh group (P = 0.658), affecting the everyday life
      of 1.1 and 2.8 per cent respectively (P = 0.448). CONCLUSION: Open inguinal
      hernia repair with a composite self-fixating mesh resulted in similar pain in the
      early postoperative convalescence period and at 1 year as repair with a sutured
      lightweight mesh.

PMID- 22362037
TI  - Regulation of mast cell survival and function by tuberous sclerosis complex 1.
AB  - Mast cells play critical roles in allergic disorders and asthma. The importance
      of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR)
      signaling in mast cells is unknown. Here, we report that TSC1 is a critical
      regulator for mTOR signaling in mast cells downstream of FcepsilonRI and c-Kit,
      and differentially controls mast cell degranulation and cytokine production. TSC1
      deficiency results in impaired mast cell degranulation, but enhanced cytokine
      production in vitro and in vivo after FcepsilonRI engagement. Furthermore, TSC1
      is critical for mast cell survival through multiple pathways of apoptosis
      including the down-regulation of p53, miR-34a, reactive oxygen species, and the
      up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical
      regulator of mast cell activation and survival, suggesting the manipulation of
      the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated
      diseases.

PMID- 22362038
TI  - Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond
      Blackfan Anemia Registry.
AB  - Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome
      characterized by red cell aplasia and congenital anomalies. A predisposition to
      cancer has been suggested but not quantified by case reports. The DBA Registry of
      North America (DBAR) is the largest established DBA patient cohort, with
      prospective follow-up since 1991. This report presents the first quantitative
      assessment of cancer incidence in DBA. Among 608 patients with 9458 person-years
      of follow-up, 15 solid tumors, 2 acute myeloid leukemias, and 2 cases of
      myelodysplastic syndrome were diagnosed at a median age of 41 years in patients
      who had not received a bone marrow transplant. Cancer incidence in DBA was
      significantly elevated. The observed-to- expected ratio for all cancers combined
      was 5.4 (P < .05); significant observed-to-expected ratios were 287 for
      myelodysplastic syndrome, 28 for acute myeloid leukemia, 36 for colon carcinoma,
      33 for osteogenic sarcoma, and 12 for female genital cancers. The median survival
      was 56 years, and the cumulative incidence of solid tumor/leukemia was
      approximately 20% by age 46 years. As in Fanconi anemia and dyskeratosis
      congenita, DBA is both an inherited bone marrow failure syndrome and a cancer
      predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia
      or dyskeratosis congenita. This trial was registered at www.clinicaltrials.gov as
      #NCT00106015.

PMID- 22362040
TI  - Intraoperative assessment of acetabular orientation:  technical note.
AB  - Acetabular surgery is frequently utilized to manage developmental dysplasia of
      the hip and hip problems associated with cerebral palsy. During the operation,
      accurate correction of the orientation of the acetabular fragment is necessary.
      We describe a technique that enables accurate assessment of the coronal plane
      alteration in orientation. Intraoperative image intensifier records were compared
      with postoperative films and the accuracy of the coronal plane correction was
      evaluated. We found the intraoperative sourcil angle closely correlated to the
      postoperative angle to within 1 degrees . The Spearman correlation coefficient
      was R=0.97, suggesting a close relationship between the two measurements.

PMID- 22362039
TI  - Unique dual targeting of thymidylate synthase and topoisomerase1 by FdUMP[10]
      results in high efficacy against AML and low toxicity.
AB  - Acute myeloid leukemia (AML) is an aggressive malignancy that leads to marrow
      failure and death. There is a desperate need for new therapies. The novel
      fluoropyrimidine, FdUMP[10], was highly active against both human AML cell lines,
      (IC(50) values, 3.4nM-21.5nM) and murine lines (IC(50) values, 123.8pM-131.4pM).
      In all cases, the IC(50) of FdUMP[10] was lower than for cytarabine and ~ 1000
      times lower than 5-fluorouracil (5-FU). FdUMP[10] remained effective against
      cells expressing the Flt3 internal tandem duplication, BCR-ABL, MN1, and an shRNA
      against p53. It had activity against patient samples at concentrations that did
      not affect normal hematopoietic cells. FdUMP[10] inhibited thymidylate synthase
      (TS) and trapped topoisomerase I cleavage complexes (Top1CCs), leading to DNA
      damage and apoptosis. All cell lines and nearly all primary AML samples examined
      expressed both TS and Top1. In vivo, FdUMP[10] was active against a syngeneic AML
      model with a survival advantage equivalent to doxorubicin plus cytarabine. 5-FU
      treatment was toxic and did not improve survival. FdUMP[10] was better tolerated
      than 5-FU or cytarabine plus doxorubicin and did not affect normal HSCs, while 5
      FU dramatically impaired their ability to engraft. In summary, FdUMP[10] was
      highly efficacious and better tolerated than standard therapies.

PMID- 22362041
TI  - Better knowledge of a disease that should be eradicated.

PMID- 22362042
TI  - Systematic review and meta-analysis of the incidence of incisional hernia at the
      site of stoma closure.
AB  - BACKGROUND: The incidence of incisional hernias at the site of stoma closure is
      surprisingly unclear. A review of the current literature was undertaken to
      determine how commonly this complication may occur and to assess the quality of
      evidence available. METHODS: A systematic review was performed to identify
      studies reporting the incidence of incisional hernia after closure of an
      ileostomy or colostomy. Studies including children (<16 years old) and studies in
      which >10% of the total number were trauma patients were excluded. RESULTS:
      Thirty-four studies provided outcomes for 2,729 closed stomas. Median follow-up
      time was 36 months but was only described in seven studies. Closure of loop
      ileostomies was the most commonly performed procedure (48%). The overall reported
      hernia rate was 7%, but with a wide range among studies (0-48%). Most studies
      based their hernia rates on retrospective clinical findings only. A separate
      analysis of three studies that were specifically designed to assess for stoma
      site hernias found the clinical hernia rate to be 30% (28/93) and the combined
      clinical/radiological hernia rate to be 35% (33/93). From 11 studies reporting
      reoperation rates, 51% of patients who developed a hernia required a surgical
      repair (34/66). There was a lower risk of hernia following reversal of ileostomy
      versus colostomy (odds ratio 0.28, 95% confidence interval 0.12-0.65).
      CONCLUSIONS: One in three patients may develop a hernia after stoma closure, and
      around half of hernias that are detected require repair. Risk of hernia is
      greater after colostomy closure than after ileostomy closure. Clinical measures
      to reduce the development of these hernias warrant consideration.

PMID- 22362043
TI  - Evolution of treatment of fistula in ano.
AB  - BACKGROUND: Fistula-in-ano is a common medical problem affecting thousands of
      patients annually. In the past, the options for treatment of fistula-in-ano were
      limited to fistulotomy and/or seton placement. Current treatment options also
      include muscle-sparing techniques such as a dermal island flap, endorectal
      advancement flap, fibrin sealent injection, anal fistula plug, and most recently
      ligation of the intersphincteric fistula tract (procedure). This study seeks to
      evaluate types and time trends for treatment of fistula-in-ano. METHODS: A
      retrospective review from 1975 to 2009 was performed. Data were collected and
      sorted into 5-year increments for type and time trends of treatment. Fistulotomy
      and partial fistulotomy were grouped as cutting procedures. Seton placement,
      fibrin sealant, dermal flap, endorectal flap, and fistula plug were grouped as
      noncutting procedures. Statistical analysis was performed for each time period to
      determine trends. RESULTS: With institutional review board approval, the records
      of 2,267 fistula operations available for analysis were included. Most of the
      patients were men (74 vs. 26%). Cutting procedures comprised 66.6% (n = 1510) of
      all procedures. Noncutting procedures were utilized in 33.4% (n = 757), including
      Seton placement alone 370 (16.3%), fibrin sealant 168 (7.4%), dermal or
      endorectal flap 147 (6.5%), and fistula plug 72 (3.2%). The distribution of
      operations grouped in 5-year intervals is as follows: 1975-1979, 78 cutting and
      one noncutting; 1980-1984, 170 cutting and 10 noncutting; 1985-1989, 54 cutting
      and five noncutting; 1990-1994, 37 cutting and six noncutting; 1995-1999, 367
      cutting and 167 noncutting; 2000-2004, 514 cutting and 283 noncutting; 2005-2009,
      290 cutting and 285 noncutting. The percentage of cutting and noncutting
      procedures significantly differed over time, with cutting procedures decreasing
      and noncutting procedures increasing proportionally (chi(2) linear-by-linear
      association, p < 0.05). CONCLUSIONS: Fistula-in-ano remains a common complex
      disease process. Its treatment has evolved to include a variety of noncutting
      techniques in addition to traditional fistulotomy. With the advent of more
      sphincter-sparing techniques, the number of patients undergoing fistulotomy
      should continue to decrease over time. Surgeons should become familiar with
      various surgical techniques so the treatment can be tailored to the patient.

PMID- 22362044
TI  - Partial small bowel resection with sleeve gastrectomy increases adiponectin
      levels and improves glucose homeostasis in obese rodents with type 2 diabetes.
AB  - BACKGROUND: The aim of this study was to examine the effect of small bowel
      resection with and without sleeve gastrectomy on glucose homeostasis in an obese
      rodent model of type 2 diabetes. METHODS: Zucker diabetic fatty rats were
      randomized into three surgical groups: Sham, small bowel resection, and small
      bowel resection with sleeve gastrectomy (BRSG). Weight and fasting glucose levels
      were measured at randomization and monitored after surgery. Oral glucose
      tolerance testing was performed at baseline and 45 days after surgery to assess
      glucose homeostasis and peptide changes. RESULTS: At baseline, all animals
      exhibited impaired glucose tolerance and showed no difference in weight or
      fasting (area under the curve) AUC(glucose). At sacrifice, Sham animals weighed
      more than BRSG animals (p = 0.047). At day 45, the Sham group experienced a
      significant increase in AUC(glucose) compared to baseline (p = 0.02), whereas
      there was no difference in AUC(glucose) in either surgical group at any time
      point: BR (p = 0.58) and BRSG (p = 0.56). Single-factor ANOVA showed a
      significant difference in AUC(glucose) of p = 0.004 between groups
      postoperatively: Sham (50,745 +/- 11,170) versus BR (23,865 +/- 432.6) (p =
      0.01); Sham versus BRSG (28,710 +/- 3188.8) (p = 0.02). There was no difference
      in plasma insulin, GLP-1, or adiponectin levels before surgery, although 45 days
      following surgery adiponectin levels where higher in the BRSG group (p = 0.004).
      CONCLUSIONS: Partial small bowel resection improved glucose tolerance independent
      of weight. The combination of small bowel resection and sleeve gastrectomy leads
      to an increase in adiponectin levels, which may contribute to improved glucose
      homeostasis.

PMID- 22362046
TI  - Common mental disorders in patients undergoing lower limb amputation: a
      population-based sample.
AB  - BACKGROUND: Amputations result in a variety of limitations that have emotional
      consequences for patients. The aim of the present study was evaluate non
      psychotic disorders and their associated factors in a sample of people with lower
      limb amputations. METHOD: A cross-sectional study was conducted that assessed the
      association of sociodemographic and clinical variables in relation to psychiatric
      disorders evaluated through the Self Reporting Questionnaire (SRQ-20) for
      patients undergoing lower limb amputation. The association between the outcome of
      the SRQ-20 and the other variables was assessed with the chi-square and Student's
      t test; to explore the magnitude of association adjusted for covariates, a
      logistic regression model was developed. RESULTS: One hundred-thirty eight (138)
      patients were interviewed, and a prevalence of 43% (60/138) was observed for
      patients with mental disorders assessed with the SRQ-20 questionnaire. We also
      observed that male patients (p = 0.017) and those who were married (p = 0.035)
      had a lower rate of psychological problems; those who were not considered
      independent (p = 0.036) and those with a greater number of morbid conditions (p =
      0.036) showed a higher positivity in relation to psychological morbidity (p =
      0.003). Logistic regression analysis showed that only the associated chronic
      diseases (p = 0.0328) and lack of independence (p = 0.0197) remained significant.
      CONCLUSIONS: Given the high prevalence of mental disorders related to the number
      of associated morbid conditions and to the situation of dependency among lower
      limb amputees, the psychological and social assessment of these people is
      recommended, in addition to encouraging their self-care and the return to their
      activities.

PMID- 22362045
TI  - Ectopic hormone-secreting pheochromocytoma: a francophone observational study.
AB  - BACKGROUND: Ectopic hormone-secreting pheochromocytomas are rare; only case
      reports exist in the literature. This condition has been linked with increased
      malignancy, familial syndromes, and ACTH secretion. We wanted to test these
      hypotheses and shed light on the nature of ectopic hormone-secreting
      pheochromocytomas. METHODS: This is a multicenter (francophone) observational
      study. Inclusion was based upon abnormal preoperative hormone tests in patients
      with pheochromocytoma that normalized after removal of the tumor. Where possible,
      immunohistochemistry was performed to confirm that ectopic secretion came from
      the tumor. RESULTS: Sixteen cases were found: nine female and seven male
      patients. Median age was 50.5 (range 31-89) years. Most presented with
      hypertension, diabetes, or cushingoid features. Ten patients had specific
      symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of
      eight patients with excess cortisol secretion, three died as a result of the
      tumor resection: two had pheochromocytomas >15 cm and their associated cortisol
      hypersecretion complicated their postoperative course. The other died from a torn
      subhepatic vein. The 13 survivors did not develop any evidence of malignancy
      during follow-up (median 50 months). Symptoms from the ectopic secretion resolved
      after removal of the tumor. Immunohistochemistry was performed and was positive
      in eight tumors: five ACTH, three calcitonins, and one VIP. CONCLUSIONS: Most
      pheochromocytomas with ectopic secretion are neither malignant nor familial. Most
      ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with
      a pheochromocytoma should be worked up for ectopic hormones, because removal of
      the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs
      careful attention.

PMID- 22362047
TI  - Selective coil embolization through flow-directed microcatheter for intracranial
      arteriovenous malformations.

PMID- 22362048
TI  - Pure spinal epidural cavernous hemangioma.
AB  - BACKGROUND: Pure epidural cavernous hemangiomas without bony involvement are
      rare, representing 4% of all spinal epidural tumors. Most of these are case
      reports and are easily misdiagnosed. METHODS: Herein nine patients (male:female,
      5:4, average age: 51 years) with symptomatic pure epidural spinal cavernous
      hemangioma between 2005 and 2011 were treated, and the clinical, radiological,
      and pathological records, treatment, and prognosis were discussed. RESULTS: All
      patients experienced a slowing progressive clinical course, except for one with
      intralesional hemorrhage. Clinical manifestations included back or radiating
      pain, sensorimotor deficits, and sphincters disturbance. Eight lesions were
      isointense on T1- and hyperintense on T2-weighted images with homogenously
      strongly enhancement and one was mixed signal with heterogeneous enhancement
      because of intratumoral hemorrhage. Hemilaminotomoy or laminotomy was performed
      and total resection was achieved. All patients experienced a gradual neurological
      improvement with no recurrence. CONCLUSIONS: Spinal epidural cavernous hemangioma
      is a benign vascular malformation that should be excluded in the diagnosis of
      epidural lesion. Total surgical resection is recommended and usually results in a
      good prognosis.

PMID- 22362049
TI  - Association of perioperative factor XIII activity levels and other haemostatic
      markers with the risk of postoperative intracranial haematoma in a selected
      cohort of neurosurgical patients.
AB  - BACKGROUND: Coagulation factor XIII and other haemostatic markers are known
      strengthen fibrin clot formation and, hence, may facilitate safer surgery.
      Currently however, factor XIII activity levels are not routinely screen.
      Therefore, the purpose of this study was to determine the association of
      perioperative factor XIII activity levels and other haemostatic markers with
      postoperative intracranial haematoma formation in neurosurgical patients.
      METHODS: Between January 2008 to Jun 2009, all neurosurgical patients who
      underwent intracranial surgery were screened for the study. Patients had blood
      samples taken preoperatively and within 24 h post-surgery for factor XIII and
      other haemostatic markers. The intracranial surgeries for the patients involved
      were performed according to their respective indications using standard
      neurosurgical techniques. Postoperatively, patients had a computed tomography
      (CT) brain scan, with the imaging results grouped into three classes: significant
      haematoma (group I), insignificant haematoma (group II) and no haematoma (group
      III). RESULTS: Of the total 84 enrolled patients, 5 (6%), 28 (33.3%) and 51
      (60.7%) patients were assigned to group I, II and III respectively. Significant
      postoperative haematoma that required re-surgery was related to low postoperative
      platelet count (p < 0.01), and higher odds ratio of developing postoperative
      intracranial haematoma were shown with two combination factors: low postoperative
      factor XIII and platelet levels; and low postoperative factor XIII and
      antithrombin levels. CONCLUSION: Low platelet count can cause significant volume
      postoperative intracranial haematoma and in presence of multiple defects in
      haemostatic markers appears to be clinically useful to predict the formation of
      postoperative intracranial haematoma in neurosurgical patients.

PMID- 22362050
TI  - iNOS-mediated secondary inflammatory response differs between rat strains
      following experimental brain contusion.
AB  - BACKGROUND: Nitric oxide is a key mediator of post-traumatic inflammation in the
      brain. We examined the expressions of iNOS, nNOS, and eNOS in inbred DA and PVGa
      rat strains where DA is susceptible to autoimmune neuroinflammation and PVGa
      resistant. METHODS: Parietal contusions using a weight drop model were produced
      in five rats per genotype. After 24 h, the brains were removed and analyzed using
      a range of immunohistochemical methods. RESULTS: PVGa presented significantly
      increased iNOS expression in infiltrating inflammatory cells in the perilesional
      area compared to DA (p < 0.05). The amount of w3/13-positive infiltrating
      inflammatory cells did not differ between strains. eNOS and nNOS expression did
      not differ between strains. iNOS-positive cells coexpressed neuronal (NeuN),
      macrophage (ED-1), and leucocyte (w3/13) markers. MnSOD was significantly
      increased in PVGa (p < 0.05). 3-Nitrotyrosine, a measure of peroxynitrite levels,
      and fluoro-jade stained neuronal degeneration, did not differ between strains.
      CONCLUSIONS: Two inbred rat strains with genetically determined differences in
      susceptibility to develop autoimmune disease displayed different levels of the
      inflammatory and anti-inflammatory mediators iNOS and MnSOD, indicating genetic
      regulation. Interestingly, the increased levels of iNOS did not lead to elevated
      expression of the neuronal cell-death marker fluoro-jade. The increased iNOS
      expression was correlated with increased expression of superoxide scavenger
      MnSOD. Excessive peroxynitrite formation was probably prevented by limitation of
      available superoxide. Subsequently, the higher expression of potentially
      deleterious iNOS in PVGa did not result in increased neuronal death.

PMID- 22362052
TI  - Diagnostic errors in the new millennium: a follow-up autopsy study.
AB  - A systematic review of the second half of the last century suggested that
      diagnostic errors have decreased over time. Our previous study covering the years
      1972-1992 was then the only time series showing a significant reduction of
      diagnostic errors from a single institution. We report here the results of a
      follow-up study a decade later. We analyzed discrepancies between clinical and
      autoptic diagnoses in 100 randomly selected medical patients who died in the
      wards and in the medical intensive care unit at a tertiary-care teaching hospital
      in Switzerland in the year 2002. Autopsy rate declined from around 90% in the
      years from 1972 to 1992 to 54% in the present study. Major diagnostic errors
      (class I and II) declined significantly from 30 to 7% (P<0.001) over the last 30
      years. Class I errors decreased from 16 to 2% (P<0.001) in the year 2002.
      Sensitivity for cardiovascular diseases increased from 69 to 92% (P=0.006), for
      infectious diseases from 25 to 90% (P=0.013) and for neoplastic diseases from 89
      to 100% (P=0.053). Specificity for cardiovascular diseases increased from 85 to
      98% (P<0.001) but was unchanged at a high level for infectious diseases and
      neoplastic diseases. The number of diagnostic procedures increased from 144 to
      281 (P<0.001) with an increase in the number of computer tomography
      investigations and of tissue sampling in the last decade. The frequency of major
      diagnostic errors has been further reduced at the beginning of the new millennium
      probably due in large part to new diagnostic tools.

PMID- 22362051
TI  - Supratentorial and infratentorial brain abscesses: surgical treatment,
      complications and outcomes--a 10-year single-center study.
AB  - OBJECTIVE: To analyze the variables determining morbidity, mortality and outcome
      in subjects with brain abscesses treated at a single center over a 10-year
      period. METHODS: A retrospective study was conducted on a series of 59 patients
      with brain abscesses surgically treated with stereotactically guided aspiration
      or open craniotomy excision. Such variables as age, gender, clinical
      presentation, number of days to diagnosis, location, number of lesions,
      predisposing factors, mechanism of infection, etiological agent, and therapy were
      analyzed independently. Complications were defined as any deviation from the
      normal postoperative course occurring within 30 days of surgery, and classified
      according to a four-point gradual severity scale. Postoperative outcome was
      appraised through the Glasgow Outcome Scale (GOS) 6 months after surgery, 0-4
      points were considered poor outcome and 5 points good outcome. RESULTS: Eighty
      abscesses were diagnosed and surgically managed in 59 patients. The mean age was
      44.69 years (range: 0.16-77); 59.3% were female. The median number of days to
      diagnosis was 7. Most frequent clinical presentations included fever (52.5%),
      headache (42.4%), and focal neurologic deficits (39%). Mechanism of infection was
      mainly hematogenous spread (32.2%). Stereotactically guided aspiration was the
      treatment of choice for 74.6% of the patients, whereas 25.4% of the cases were
      managed through open craniotomy excision. Outcome was favorable in 81.35% (n =
      48) of the subjects. General morbidity was 27.1%, and mortality stood at 10.16%.
      Out of a total 38.98% (n = 23) of complications, two-thirds were due to medical
      causes. The analysis of variables revealed that only age (p = 0.02),
      immunosuppression (OR 5.83; p = 0.012) and hematogenous spread (p < 0.01) were
      associated with poor outcomes. CONCLUSIONS: Immunosuppression, hematogenous
      spread and advanced age were predictors of poor prognosis. Most of the
      complications following brain abscess management were not directly related to
      surgery or surgical technique.

PMID- 22362053
TI  - New methods for clinical pathways-Business Process Modeling Notation (BPMN) and
      Tangible Business Process Modeling (t.BPM).
AB  - PURPOSE: Clinical pathways (CP) are nowadays used in numerous institutions, but
      their real impact is still a matter of debate. The optimal design of a clinical
      pathway remains unclear and is mainly determined by the expectations of the
      individual institution. The purpose of the here described pilot project was the
      development of two CP (colon and rectum carcinoma) according to Business Process
      Modeling Notation (BPMN) and Tangible Business Process Modeling (t.BPM). METHODS:
      BPMN is an established standard for business process modelling in industry and
      economy. It is, in the broadest sense, a computer programme which enables the
      description and a relatively easy graphical imaging of complex processes. t.BPM
      is a modular construction system of the BPMN symbols which enables the creation
      of an outline or raw model, e.g. by placing the symbols on a spread-out paper
      sheet. The thus created outline can then be transferred to the computer and
      further modified as required. CP for the treatment of colon and rectal cancer
      have been developed with support of an external IT coach. RESULTS: The pathway
      was developed in an interdisciplinary and interprofessional manner (55 man-days
      over 15 working days). During this time, necessary interviews with medical,
      nursing and administrative staffs were conducted as well. Both pathways were
      developed parallel. Subsequent analysis was focussed on feasibility, expenditure,
      clarity and suitability for daily clinical practice. The familiarization with
      BPMN was relatively quick and intuitive. The use of t.BPM enabled the pragmatic,
      effective and results-directed creation of outlines for the CP. The development
      of both CP was finished from the diagnostic evaluation to the
      adjuvant/neoadjuvant therapy and rehabilitation phase. The integration of
      checklists, guidelines and important medical or other documents is easily
      accomplished. A direct integration into the hospital computer system is currently
      not possible for technical reasons. CONCLUSION: BPMN and t.BPM are sufficiently
      suitable for the planned modelling and imaging of CP. The application in medicine
      is new, and transfer from the industrial process management is in principle
      possible. BPMN-CP may be used for teaching and training, patient information and
      quality management. The graphical image is clearly structured and appealing. Even
      though the efficiency in the creation of BPMN-CP increases markedly after the
      training phase, high amounts of manpower and time are required. The most sensible
      and consequent application of a BPMN-CP would be the direct integration into the
      hospital computer system. The integration of a modelling language, such as BPMN,
      into the hospital computer systems could be a very sensible approach for the
      development of new hospital information systems in the future.

PMID- 22362055
TI  - How to ensure the survival of the surgeon-scientist? The Homburg Program.
AB  - BACKGROUND: Academic surgery requires competence in research, teaching, and
      patient care. Because of the increasing complexity of both surgical research and
      clinical surgery, and additional skills necessary for adequate patient care,
      including economics, management, and organization, it becomes more and more
      difficult to provide an attractive education for surgeon-scientists. This has
      resulted in a dramatic decline in the number of surgeon-scientists in the past
      and alarms us to systematically restructure our research training system.
      DISCUSSION: We herein introduce a program involving the clinical departments of
      surgery, trauma surgery, and cardiac-thoracic surgery as well as a surgical
      research institution. The program allows the clinical departments to sharpen
      their overall research profile and facilitates the establishment of competent
      working groups, guaranteeing long-term research activities on a high scientific
      level. The program involves both surgical residents and medical students, who
      will represent our future generation of academic surgeons, ensuring the survival
      of the surgeon-scientist.

PMID- 22362054
TI  - Lynch syndrome: clinical, pathological, and genetic insights.
AB  - INTRODUCTION: Lynch syndrome as the most common hereditary colorectal cancer
      syndrome and the most common cause of hereditary endometrial cancer is
      characterized by an autosomal dominant inheritance with a penetrance of 85-90%.
      The molecular genetic underlying mechanism is a mutation in one of the mismatch
      repair genes. METHODS: In order to identify patients with Lynch syndrome, a
      nuclear family history should be ascertained and matched with the Amsterdam
      criteria. A different approach for identification is the adherence to Bethesda
      criteria and subsequent testing for microsatellite instability. In patients with
      unstable tumors as an indicator for mismatch repair deficiency, genetic
      counseling and mutation analysis are warranted. For families fulfilling the
      Amsterdam criteria, intensified screening is recommended, even if a pathogenic
      mutation is not identified. RESULTS: Individuals from families with a proven
      pathogenic mutation that are tested negative are at normal population risk for
      cancers and may be dismissed from intensified surveillance. Prophylactic surgery
      in high-risk individuals without neoplasia is not generally recommended. At the
      time of a colon primary, however, extended surgery should be discussed in the
      light of a high rate of metachronous cancers. The worries of impairing functional
      results have now been evaluated in the light of quality of life in a large
      international cohort. Interestingly, extended (prophylactic) surgery does not
      lead to inferior quality of life with equal perioperative risks. CONCLUSIONS:
      Therefore, taking the risk reduction into account, extended surgery at the time
      of the first colon primary should at least be discussed, if not recommended.
      Also, prophylactic hysterectomy and bilateral oophorectomy at the time of a
      colorectal primary should be recommended if family planning has been completed.

PMID- 22362056
TI  - Protective effect of Phyllanthus fraternus against mitochondrial dysfunction
      induced by co-administration of cisplatin and cyclophosphamide.
AB  - The evolving role of mitochondria, in mediating chemotherapy-induced apoptosis
      motivated us for the studies described here. The combination of cisplatin and
      cyclophosphamide is widely used in treating various types of cancers. The purpose
      of our study was to understand the mechanism of the toxicity induced by the co
      administration of cisplatin and cyclophosphamide, on mitochondrial bioenergetics,
      and to study the protective effect of prior administration of the medicinal plant
      extract Phyllanthus fraternus. Our results reveal that co-administration of
      cisplatin (12 mg/kg, i.p) and cyclophosphamide (150 mg/kg, oral) to wistar rats
      (100 g) significantly alters mitochondrial structure and hence function. The rate
      of mitochondrial respiration was decreased significantly with both NAD + and FAD
      linked substrates. The respiratory control ratio, an index of membrane integrity
      and the P/O ratio, a measure of phosphorylating efficiency also were decreased
      significantly accompanied by elevation in the lipid peroxide levels in liver,
      kidney homogenate and liver mitochondria respectively. Also, the phospholipid
      content of the mitochondrial membrane, showed a significant decrease, indicating
      mitochondrial membrane changes. Prior administration of an aqueous extract of P.
      fraternus (100 mg/kg) to rats, showed protection on all parameters investigated.
      Administration of P. fraternus alone did not show any significant changes on
      mitochondrial membrane bioenergetics. Thus, we propose, that the toxic side
      effects of cisplatin (+) cyclophosphamide, are due to a chain of interconnected
      events, within the mitochondrial inner membrane, ultimately leading to
      hepatotoxicity and nephrotoxicity. Further, our work also suggests that
      administration of aqueous extract of P. fraternus can enhance the therapeutic
      potential of anticancer drugs by reducing drug related toxicity.

PMID- 22362057
TI  - Cone beam computed tomography in mandibular molars referred for apical surgery.
AB  - INTRODUCTION: The purpose of the present study was to compare conventional
      intraoral periapical radiographs (PA) with limited cone beam computed tomography
      (CBCT) for evaluation of mandibular molars prior to apical surgery. The apical
      extent and homogeneity of the root canal fillings (RCF) as well as the number of
      root canals were examined. METHODS: 38 molars with 75 roots were included in the
      study. The apical extent and homogeneity of the RCFs as well as the presence of
      root canal posts or screws were examined on sagittal CBCT slices and on the PAs.
      The number of root canals was determined on sagittal CBCT slices and the PAs. The
      mesial and the distal roots were examined separately. RESULTS: Considerably more
      root canals were found on the CBCT slices compared to the PAs. The homogeneity
      and the extent of the RCFs as well as the presence of root canal posts or screws
      seem subjectively easier to determine on the PAs. CONCLUSION: In mandibular
      molars, because of the better discrimination of root canal anatomy we recommend a
      CBCT scan prior to apical surgery.

PMID- 22362059
TI  - Sleep duration and endometrial cancer risk.
AB  - PURPOSE: Recent data indicate that night shift work is associated with increased
      endometrial cancer risk, perhaps through a pathway involving lower melatonin
      production. Melatonin is an antiestrogenic hormone, with production in a
      circadian pattern that is dependent on presence of dark at night. Sleep duration
      is positively associated with melatonin production and may be an indicator of
      melatonin levels in epidemiologic studies. METHODS: We evaluated associations
      between self-reported sleep duration and endometrial cancer risk using publicly
      available prospective data on 48,725 participants in the Women's Health
      Initiative Observational Study, among whom 452 adjudicated incident cases of
      endometrial cancer were diagnosed over approximately 7.5 years of follow-up.
      Sleep duration was self-reported at baseline. Cox proportional hazards regression
      was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for
      endometrial cancer risk with adjustment for potential confounders. RESULTS: Most
      women reported sleeping <= 6 (33.3%) or 7 (38.5%) h each night; fewer reported
      sleeping 8 (23.4%) or >= 9 (4.8%) h each night. In adjusted analyses, there was
      an indication of reduced risk associated with longer sleep duration, though no
      statistically significant association was observed. Women who slept >= 9 h had a
      nonsignificant reduced risk of endometrial cancer compared with women who slept
      <= 6 h (HR = 0.87; 95% CI = 0.51-1.46). CONCLUSIONS: We found weak evidence of an
      association between sleep duration and endometrial cancer risk. Self-reported
      sleep duration may not adequately represent melatonin levels, thus further
      studies utilizing urinary melatonin levels are necessary to establish the
      mechanism by which night shift work increases endometrial cancer risk.

PMID- 22362058
TI  - Perceived effectiveness of pictorial health warnings among Mexican youth and
      adults: a population-level intervention with potential to reduce tobacco-related
      inequities.
AB  - PURPOSE: Pictorial health warnings on cigarette packages are a prominent and
      effective means of communicating the risks of smoking; however, there is little
      research on effective types of message content and socio-demographic effects.
      This study tested message themes and content of pictorial warnings in Mexico.
      METHODS: Face-to-face surveys were conducted with 544 adult smokers and 528 youth
      in Mexico City. Participants were randomized to view 5-7 warnings for two of 15
      different health effects. Warnings for each health effect included a text-only
      warning and pictorial warnings with various themes: "graphic" health effects,
      "lived experience", symbolic images, and testimonials. RESULTS: Pictorial health
      warnings were rated as more effective than text-only warnings. Pictorial warnings
      featuring "graphic" depictions of disease were significantly more effective than
      symbolic images or experiences of human suffering. Adding testimonial information
      to warnings increased perceived effectiveness. Adults who were female, older, had
      lower education, and intended to quit smoking rated warnings as more effective,
      although the magnitude of these differences was modest. Few interactions were
      observed between socio-demographics and message theme. CONCLUSIONS: Graphic
      depictions of disease were perceived by youth and adults as the most effective
      warning theme. Perceptions of warnings were generally similar across socio
      demographic groups.

PMID- 22362060
TI  - [Trends in the prevalence of malaria and anemia at delivery in Libreville from
      1995 to 2011].
AB  - In 1995, 2005 and 2011, cross-sectional studies of 611 parturients at the Centre
      Hospitalier de Libreville in Gabon assessed the prevalence of maternal malaria
      and anaemia; two indicators of poor pregnancy outcomes. The prevalence of
      Plasmodium falciparum infection in maternal peripheral blood decreased from 25%
      in 2005 to 6% in 2011. Parasite density was significantly lower in 2005 (31
      p/MUL) than in 1995 (1,240 p/MUL) or 2011 (35,055 p/MUL). Anaemia prevalence was
      high (>50%) in 1995 and in 2005, but fell by more than 50% (24%) in 2011. After
      implementation of new malaria prevention strategies during pregnancy, the
      prevalence of both maternal peripheral P. falciparum infection and anaemia fell.
      Studies are necessary to assess the efficacy of these strategies and to seek
      other causes of anaemia.

PMID- 22362061
TI  - Photoelectron spectroscopy of silicon doped gold and silver cluster anions.
AB  - Photoelectron spectra of low temperature silicon doped gold cluster anions
      Au(n)Si(-) with n = 2-56 and silver cluster anions Ag(n)Si(-) with n = 5-82 have
      been measured. Comparing the spectra as well as the general size dependence of
      the electron detachment energies to the results on undoped clusters shows that
      the silicon atom changes the apparent free electron count in the clusters. In the
      case of larger gold clusters (with more than about 30 gold atoms) the silicon
      atom seems to consistently delocalize all of its four valence electrons, while in
      the case of the silver clusters a less uniform behavior is observed. Here the
      silicon atoms act partly as electron donors, partly as electron acceptors,
      without following an obvious simple principle. Additionally some structural
      information can be obtained from the measured spectra: while Ag(54)Si(-) seems to
      adopt an icosahedral structural motif, Au(54)Si(-) seems to take on a low
      symmetry structure, much like the corresponding pure 55 atom clusters. This
      indicates that for such larger clusters the incorporation of a single silicon
      atom does not change the ground state geometry significantly.

PMID- 22362062
TI  - Use of electronic results reporting to diagnose and monitor AKI in hospitalized
      patients.
AB  - BACKGROUND AND OBJECTIVES: Many patients with AKI are cared for by non
      nephrologists. This can result in variable standards of care that contribute to
      poor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To improve AKI
      recognition, a real-time, hospital-wide, electronic reporting system was designed
      based on current Acute Kidney Injury Network criteria. This system allowed
      prospective data collection on AKI incidence and outcomes such as mortality rate,
      length of hospital stay, and renal recovery. The setting was a 1139-bed teaching
      hospital with a tertiary referral nephrology unit. RESULTS: An electronic
      reporting system was successfully introduced into clinical practice (false
      positive rate, 1.7%; false negative rate, 0.2%). The results showed that there
      were 3202 AKI episodes in 2619 patients during the 9-month study period (5.4% of
      hospital admissions). The in-hospital mortality rate was 23.8% and increased with
      more severe AKI (16.1% for stage 1 AKI versus 36.1% for stage 3) (P<0.001). More
      severe AKI was associated with longer length of hospital stay for stage 1 (8
      days; interquartile range, 13) versus 11 days for stage 3 (interquartile range,
      16) (P<0.001) and reduced chance of renal recovery (80.0% in stage 1 AKI versus
      58.8% in stage 3) (P<0.001). Utility of the Acute Kidney Injury Network criteria
      was reduced in those with pre-existing CKD. CONCLUSIONS: AKI is common in
      hospitalized patients and is associated with very poor outcomes. The successful
      implementation of electronic alert systems to aid early recognition of AKI across
      all acute specialties is one strategy that may help raise standards of care.

PMID- 22362063
TI  - Acute effects of very-low-protein diet on FGF23 levels: a randomized study.
AB  - BACKGROUND AND OBJECTIVES: High levels of fibroblast growth factor 23 are
      associated with mortality, CKD progression, and calcification in CKD patients.
      The aim of this pilot study is to assess whether a very-low-protein diet (0.3
      g/kg per day) with a consequent low intake of phosphorus would reduce fibroblast
      growth factor 23 compared with a low-protein diet (0.6 g/kg per day) in CKD
      patients not yet on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      prospective, randomized, controlled crossover study was performed in which 32
      patients were randomized into two groups. Group A (16 patients) received a very
      low-protein diet (0.3 g/kg body wt per day) supplemented with ketoanalogues
      during the first week and a low-protein diet during the second week, and group B
      (16 patients) received a low-protein diet during the first week and a very-low
      protein diet during the second week. Fibroblast growth factor 23, seric, and
      urinary phosphate levels were measured at baseline and the end of each study
      period. RESULTS: After only 1 week of the very-low-protein diet, reductions in
      fibroblast growth factor 23 levels (33.5%), serum phosphate (12%), and urinary
      phosphate (34%) with the very-low-protein diet compared with the low-protein diet
      were observed. Serum and urinary phosphate levels and protein intake were
      significant determinants of fibroblast growth factor 23 (95% confidence
      interval=1.04-1.19, 1.12-1.37, and 1.51-2.23, respectively). CONCLUSIONS: A very
      low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor
      23 levels in CKD patients not yet on dialysis.

PMID- 22362064
TI  - Fluoroscopic manipulation of peritoneal dialysis catheters: outcomes and factors
      associated with successful manipulation.
AB  - BACKGROUND AND OBJECTIVES: Mechanical failure of the peritoneal dialysis (PD)
      catheter is an important cause of technique failure. Fluoroscopic guidewire
      manipulation may be undertaken in an attempt to correct the failure. The purpose
      of this study was to determine the efficacy of fluoroscopic manipulation of
      previously embedded PD catheters, the factors associated with successful
      manipulation, and the complication rate associated with manipulation. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: A single-center, retrospective review of
      70 consecutive PD patients undergoing fluoroscopic manipulation for mechanical
      failure of their PD catheter from June 2006 to February 2011 was undertaken.
      Logistic regression models were developed to determine the variables associated
      with successful manipulation. RESULTS: Of the 70 manipulations, 44 were
      successful (62.9%). In univariate analysis, catheters located in the pelvis
      compared with those in the upper abdomen (73.5% versus 42.9%, P=0.01) and
      catheters that were previously functional compared with those that failed at
      exteriorization (75.0% versus 46.7%, P=0.04) were more likely to be successfully
      manipulated. Time embedded, previous hemodialysis, and number of intra-abdominal
      surgeries were not correlated with likelihood of successful manipulation. In
      multivariate analysis, catheters located in the pelvis (P=0.01) and those with
      secondary failure (P=0.01) were more likely to successfully manipulated. Two of
      the patients developed peritonitis (2.9%), neither requiring cessation of PD.
      CONCLUSIONS: Fluoroscopic manipulation is an effective and safe therapy for
      failed PD catheters that are unresponsive to conservative treatment. Properly
      positioned catheters and those that were previously functional are more likely to
      be successfully manipulated.

PMID- 22362066
TI  - Global analysis of protein phosphorylation networks in insulin signaling by
      sequential enrichment of phosphoproteins and phosphopeptides.
AB  - Although the important role of protein phosphorylation in insulin signaling
      networks is well recognized, its analysis in vivo has not been pursued in a
      systematic fashion through proteome-wide studies. Here we undertake a global
      analysis of insulin-induced changes in the rat liver cytoplasmic and endosomal
      phosphoproteome by sequential enrichment of phosphoproteins and phosphopeptides.
      After subcellular fractionation proteins were denatured and loaded onto
      iminodiacetic acid-modified Sepharose with immobilized Al3+ ions (IMAC-Al resin).
      Retained phosphoproteins were eluted with 50 mM phosphate and proteolytically
      digested. The digest was then loaded onto an IMAC-Al resin and phosphopeptides
      were eluted with 50 mM phosphate, and resolved by 2-dimensional liquid
      chromatography, which combined offline weak anion exchange and online reverse
      phase separations. The peptides were identified by tandem mass spectrometry,
      which also detected the phosphorylation sites. Non-phosphorylated peptides found
      in the flow-through of the IMAC-Al columns were also analyzed providing
      complementary information for protein identification. In this study we enriched
      phosphopeptides to ~85% purity and identified 1456 phosphopeptides from 604 liver
      phosphoproteins. Eighty-nine phosphosites including 45 novel ones in 83 proteins
      involved in vesicular transport, metabolism, cell motility and structure, gene
      expression and various signaling pathways were changed in response to insulin
      treatment. Together these findings could provide potential new markers for
      evaluating insulin action and resistance in obesity and diabetes.

PMID- 22362065
TI  - Combined use of vitamin D status and FGF23 for risk stratification of renal
      outcome.
AB  - BACKGROUND AND OBJECTIVES: Hyperphosphatemia, vitamin D deficiency,
      hyperparathyroidism, and high serum fibroblast growth factor 23 (FGF23) levels,
      when studied separately, were found to predict the progression of CKD. However,
      studies with simultaneous measurement of mineral bone disorder (MBD)-related
      factors were scarce. This study aimed to identify factors predicting renal
      outcome independent of other factors. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This was a prospective cohort study of 738 Japanese predialysis
      outpatients in the nephrology departments of two hospitals. The outcome was
      defined as a doubling of serum creatinine or initiation of dialysis. RESULTS:
      Mean estimated GFR (eGFR) was 35 ml/min per 1.73 m(2). At enrollment, the
      increase in intact FGF23 with decreasing eGFR was the earliest among changes in
      MBD-related factors, followed by 1,25-dihydroxyvitamin D decrease, parathyroid
      hormone increase, and phosphate increase. During a median duration of 4.4 years,
      213 patients reached the endpoint. In a multivariable Cox model, high FGF23 and
      low 25-hydroxyvitamin D (25D) levels were the only MBD-related factors associated
      with a higher risk of renal endpoint (adjusted hazard ratio [95% confidence
      interval] per unit change of log FGF23 and 10 ng/ml of 25D: 1.83 [1.28-2.61] and
      0.61 [0.41-0.90], respectively). There was no significant interaction between 25D
      and FGF23 (P=0.11). Active vitamin D therapy, serum phosphate, 1,25
      dihydroxyvitamin D, and parathyroid hormone levels were not related to the renal
      endpoint. Treating death as a competing risk or multiple imputation for missing
      values yielded similar results. CONCLUSIONS: Combined use of two markers is
      useful for the risk stratification of renal outcome.

PMID- 22362067
TI  - Enhancement of the electrocatalytic activity of Pt nanoparticles in oxygen
      reduction by chlorophenyl functionalization.
AB  - Chlorophenyl-stabilized platinum nanoparticles (1.85 nm) exhibited
      electrocatalytic activity for oxygen reduction up to 3 times higher than that of
      commercial Pt/C catalysts. Similar enhancement was observed with naked Pt/C
      functionalized by the same chlorophenyl fragments, suggesting the important role
      of organic capping ligands in the manipulation of nanoparticle electrocatalytic
      performance.

PMID- 22362068
TI  - Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced
      apoptosis and cytotoxicity.
AB  - The most prominent capabilities of mesenchymal stem cells (MCSs) which make them
      promising for therapeutic applications are their capacity to endure and implant
      in the target tissue. However, the therapeutic applications of these cells are
      limited due to their early death within the first few days following
      transplantation. Therefore, to improve cell therapy efficacy, it is necessary to
      manipulate MSCs to resist severe stresses imposed by microenvironment. In this
      study, we manipulated MSCs to express a cytoprotective factor, nuclear factor
      erythroid-2 related factor 2 (Nrf2) to address this issue. Full-length human Nrf2
      cDNA was isolated and TOPO cloned into TOPO cloning vector and then transferred
      to gateway adapted adenovirus expression vector by LR recombination reaction.
      Afterwards, the Nrf2 bearing recombinant virus was prepared in appropriate
      mammalian cell line and used to infect MSCs. The viability and apoptosis of the
      Nrf2 expressing MSCs were evaluated following hypoxic and oxidative stress
      conditions. Transient expression of Nrf2 by MSCs protected them against cell
      death and the apoptosis triggered by hypoxic and oxidative stress conditions.
      Nrf2 also enhanced the activity of SOD and HO-1. These findings could be used as
      a strategy for prevention of graft cell death in MSC-based cell therapy. It also
      indicates that management of cellular stress responses can be used for practical
      applications.

PMID- 22362069
TI  - Complementary strand microRNAs mediate acquisition of metastatic potential in
      colonic adenocarcinoma.
AB  - BACKGROUND: Altered expression of specific microRNAs (miRNA) is known to occur
      during colorectal carcinogenesis. However, little is known about the genome-wide
      alterations in miRNA expression during the neoplastic progression of primary
      colorectal cancers. METHODS: Using a miRNA array platform, we evaluated the
      expression of 668 miRNA in primary colonic adenocarcinomas. Biological functions
      of selected miRNA were evaluated with in vitro invasion assays. RESULTS: RNA was
      extracted for miRNA analysis from 65 primary colon cancers. We identified a seven
      miRNA expression signature that differentiated stage I and stage IV primary colon
      cancers. We then demonstrated this signature was able to discriminate between
      stage II and III primary colon cancers. Six differentially expressed miRNA were
      downregulated in association with the development of metastases, and all 7 miRNA
      were complementary strand miRNA. We transfected HCT-116, a highly invasive colon
      cancer cell line, with corresponding downregulated miRNA and demonstrated that
      overexpression of three miRNA (miR200c*, miR143*, and miR424*) significantly
      abrogated invasive potential. CONCLUSION: We have identified a seven-miRNA
      signature that is associated with metastatic potential in the primary tumor.
      Forced overexpression of three downregulated miRNA resulted in attenuation of in
      vitro invasion, suggesting direct tumor suppressive function and further
      supporting the biological importance of complementary strand miRNA.

PMID- 22362072
TI  - The therapeutic potential of metal-based antimalarial agents: implications for
      the mechanism of action.
AB  - Despite recent encouraging advances against the disease, malaria remains a major
      public health problem affecting almost half a billion people and killing almost a
      million per annum. Due to a short arsenal of efficient antimalarial agents and
      the frequent appearance of resistance to the drugs in current use, which
      consequently reduce our means to treat patients, there is a very urgent and
      continuous need to develop new compounds. This perspective outlines a unique
      strategy for that purpose through the development of metal-based antimalarial
      agents. The examples presented here illustrate an attractive alternative to
      classical drugs.

PMID- 22362071
TI  - Rt-PCR increases detection of submicroscopic peritoneal metastases in gastric
      cancer and has prognostic significance.
AB  - BACKGROUND: Positive peritoneal cytology confers the same prognosis as clinical
      stage IV disease in gastric cancer. Conventional cytology examination, however,
      has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT
      PCR) may have increased sensitivity and provide more accurate staging
      information. METHODS: From February 2007 to April 2009, peritoneal lavage samples
      were collected prospectively from 156 patients with biopsy-proven gastric cancer
      undergoing staging laparoscopy. These washings were analyzed by both Papanicolaou
      staining and RT-PCR for the tumor marker carcinoembryonic antigen (CEA). RESULTS:
      Visible peritoneal disease was seen at laparoscopy in 38 patients (LAP+, 24%).
      Cytology was positive (CYT+) in 23 patients, while RT-PCR was positive (PCR+) in
      30. The sensitivity of CYT for the detection of visible disease was 61% compared
      to 79% for PCR (P = 0.02). No visible peritoneal disease was seen at laparoscopy
      (LAP-) in 118 (76%) patients. Eight (7%) were CYT+, while 28 (24%) were PCR+.
      Predictors of PCR positivity included advanced-stage disease (T3-4 vs. T1-2
      tumors) and poor pathologic features such as vascular or perineural invasion.
      Long-term follow-up demonstrated a worse survival of LAP-CYT-PCR+ (P = 0.0003)
      and LAP-CYT+PCR+ (P = 0.0004) compared to LAP-CYT-PCR- patients. There was no
      significant difference in survival between CYT-PCR+ and CYT+PCR+ patients. PCR
      positivity also predicted a higher likelihood of disease recurrence after
      resection. An R0 resection was performed in 85 LAP- patients (54%): only 1 (1%)
      was CYT+, while 13 (15%) were PCR+. Of this group, PCR+ demonstrated a worse
      survival than PCR- patients (P = 0.02). Further analysis showed that, in R0
      resection, stage III/IV, CYT- subgroup, PCR+ was associated with a trend towards
      worse survival (P = 0.09) compared to PCR- patients. CONCLUSION: RT-PCR for CEA
      increases the detection of subclinical peritoneal disease and is more sensitive
      than cytology. Predictors of positive PCR included advanced-stage disease,
      vascular invasion, and perineural invasion. PCR positivity was associated with
      increased disease recurrence and decreased survival. Further follow-up is
      required to determine if PCR positivity alone is an independent predictor of poor
      survival in gastric cancer.

PMID- 22362073
TI  - Highlights in prostate cancer from the 2011 American Urological Association
      Annual Meeting and the 2011 American Society of Clinical Oncology Annual Meeting.

PMID- 22362070
TI  - Summary of at the 45th annual Pancreas Club meeting proceedings.
AB  - BACKGROUND: The 45th meeting of the Pancreas Club was held on 5 and 6 May 2011 at
      the Robert H. Lurie Medical Research Center in Chicago, IL. An outstanding
      program of 47 oral presentations (Table 1) and 137 poster presentations was
      chosen from a record number of submitted abstracts. Ten posters each day were
      chosen for presentation as part of the Professor Rounds portion of the formal
      poster viewing program. Summaries of the oral presentations are provided;
      published work is referenced. Full abstracts are available on the Pancreas Club
      website: http://pancreasclub.com.

PMID- 22362074
TI  - Mechanical recanalization of subacute vessel occlusion in peripheral arterial
      disease with a directional atherectomy catheter.
AB  - PURPOSE: To retrospectively examine the technical feasibility and safety of
      directional atherectomy for treatment of subacute infrainguinal arterial vessel
      occlusions. METHODS: Five patients (one woman, four men, age range 51-81 years)
      with peripheral arterial disease who experienced sudden worsening of their
      peripheral arterial disease-related symptoms during the last 2-6 weeks underwent
      digital subtraction angiography, which revealed vessel occlusion in native
      popliteal artery (n = 4) and in-stent occlusion of the superficial femoral artery
      (n = 1). Subsequently, all patients were treated by atherectomy with the
      SilverHawk (ev3 Endovascular, USA) device. RESULTS: The mean diameter of treated
      vessels was 5.1 +/- 1.0 mm. The length of the occlusion ranged 2-14 cm. The
      primary technical success rate was 100%. One patient experienced a reocclusion
      during hospitalization due to heparin-induced thrombocytopenia. There were no
      further periprocedural complications, in particular no peripheral embolizations,
      until hospital discharge or during the follow-up period of 1 year. CONCLUSION:
      The recanalization of infrainguinal arterial vessel occlusions by atherectomy
      with the SilverHawk device is technically feasible and safe. In our limited
      retrospective study, it was associated with a high technical success rate and a
      low procedure-related complication rate.

PMID- 22362076
TI  - Retraction.

PMID- 22362075
TI  - Needle-like Zn-doped SnO2 nanorods with enhanced photocatalytic and gas sensing
      properties.
AB  - Zn-doped SnO(2) nanorods have been prepared by a simple hydrothermal method on a
      large scale. The as-prepared samples were characterized by x-ray powder
      diffraction, scanning electron microscope, transmission electron microscope,
      energy dispersive spectrometer, x-ray photoelectron spectroscopy, UV-vis
      absorption spectra and photoluminescence spectra. Studies found that the products
      are needle-like single-crystalline nanorods grown along the [[Formula: see text]]
      orientation. The photocatalytic properties of the synthesized Zn-doped SnO(2)
      were investigated by decomposing acid fuchsine, showing much higher
      photocatalytic activity than pure SnO(2) nanorods and bulk SnO(2) powders. An
      enhanced gas sensing ability toward methanal, ethanol and acetone gases is also
      achieved in high sensitivity and fast response. The origins of the enhanced
      performances are discussed.

PMID- 22362077
TI  - Cystic schwannoma of a seminal vesicle.
AB  - We present a case of a cystic schwannoma of the seminal vesicle that  occurred in
      a 50-year-old man who presented asymptomatic. Computed tomography  scan and
      magnetic resonance imaging revealed a cystic mass within the left  seminal
      vesicle. A laparoscopic surgery was performed to remove the mass on  request.
      Histopathological examination finally confirmed a schwannoma of the  seminal
      vesicle. The patient was free of disease 3 months postoperatively.

PMID- 22362078
TI  - Arterial erectile dysfunction and peripheral arterial disease: reliability of a
      new phenotype of endothelial progenitor cells and endothelial microparticles.
AB  - The aim of this study was to evaluate whether the blood concentrations of a  new
      immunophenotype of circulating late endothelial progenitor cells (EPC) and 
      endothelial microparticles (EMP) varies in patients with arterial erectile 
      dysfunction (aED) and abnormalities in other arterial districts. To accomplish 
      this, cavernous artery peak systolic velocity (PSV), acceleration time (AT),  and
      intima-media thickness (IMT) were determined after intracavernous  administration
      of alprostadil by echo-color Doppler in 80 consecutive patients  (age range, 50
      75 years). Fifteen patients had aED alone (group A) and  served as controls; 22
      had aED plus atheroma plaques and/or increased IMT of  the common carotid artery
      (group B); 20 had aED plus lower limb artery  abnormalities (group C); and 23 had
      aED plus carotid and lower limb artery  abnormalities (group D). EPC and EMP
      blood concentrations were evaluated by  flow cytometry. Blood mononuclear cells
      with the immunophenotype  CD45(neg)/CD34(pos)/CD144(pos) were defined as  EPCs,
      whereas CD45(neg)/CD144(pos)/annexin V(pos)  cells were defined as EMPs. Group B
      and C patients had a similar PSV, AT, and  IMT at the level of the cavernous
      arteries. Their PSV values were  significantly lower and mean values of AT and
      IMT significantly higher  compared with group A patients. Patients of group D had
      a significantly lower  PSV and significantly higher AT and IMT compared with all
      other groups. As far  as serum concentrations of EPCs and EMPs, group D patients
      had significantly  higher EPC and EMP mean values compared with all other groups.
      Group B and C  patients had similar EPC and EMP values. This study showed that a
      more  generalized peripheral atherosclerotic process is associated with a more 
      severe penile artery insufficiency and endothelial dysfunction. Moreover, this 
      study confirms the diagnostic reliability of the immunophenotype of EPCs and 
      EMPs chosen in the clinical practice.

PMID- 22362079
TI  - Plasma levels of platelet-derived microparticles are increased after anaerobic
      exercise in healthy subjects.

PMID- 22362080
TI  - Partial genetic turnover in neandertals: continuity in the East and population
      replacement in the West.
AB  - Remarkably little is known about the population-level processes leading up to the
      extinction of the neandertal. To examine this, we use mitochondrial DNA sequences
      from 13 neandertal individuals, including a novel sequence from northern Spain,
      to examine neandertal demographic history. Our analyses indicate that recent
      western European neandertals (<48 kyr) constitute a tightly defined group with
      low mitochondrial genetic variation in comparison with both eastern and older
      (>48 kyr) European neandertals. Using control region sequences, Bayesian
      demographic simulations provide higher support for a model of population
      fragmentation followed by separate demographic trajectories in subpopulations
      over a null model of a single stable population. The most parsimonious
      explanation for these results is that of a population turnover in western Europe
      during early Marine Isotope Stage 3, predating the arrival of anatomically modern
      humans in the region.

PMID- 22362081
TI  - Comparative genomics reveals adaptive protein evolution and a possible
      cytonuclear incompatibility between European and American Eels.
AB  - During the early stages of speciation, interspecific gene flow may be impeded by
      deleterious epistatic interactions in hybrids, which maintain parental allelic
      combinations at the speciation genes. The resulting semipermeable nature of the
      barrier to interspecific gene flow provides a valuable framework to identify the
      genes involved in hybrid mortality or sterility, as well as the evolutionary
      mechanisms that initially caused their divergence. The two Atlantic eels Anguilla
      anguilla and A. rostrata are partially isolated sister species that naturally
      hybridize, but whose genetic basis of postzygotic isolation remains unknown. We
      collected high-throughput sequencing data from the transcriptomes of 58
      individuals and discovered 94 genes showing differentially fixed mutations
      between species. Evidence for positive selection at nuclear diagnostic genes was
      obtained using multilocus extensions of the McDonald-Kreitman test with
      polymorphism data from each species. In contrast, mitochondrial protein-coding
      genes experienced strong purifying selection and mostly diverged at synonymous
      sites, except for the mt-atp6 gene, which showed an atypically high nonsynonymous
      to synonymous rate ratio. Nuclear-encoded protein interactors of the mt-atp6 gene
      in the ATP synthase complex were significantly overrepresented in the list of
      nuclear diagnostic genes. Further analysis of resequencing data showed that
      positive selection has operated at both the mt-atp6 gene and its nuclear
      interactor atp5c1. These findings suggest that a cytonuclear incompatibility
      caused by a disruption of normal ATP synthase function in hybrids contributes to
      partial reproductive isolation between European and American eels.

PMID- 22362082
TI  - Impaired cerebral and systemic hemodynamics under cognitive load in young
      hypotensives: a transcranial Doppler study.
AB  - Reduced sympathetic outflow and deficits in cerebral hemodynamics have been
      considered as possible factors mediating the impaired cognitive performance in
      essential hypotension. However, the relationship between systemic blood pressure
      (BP), cerebral blood flow and cognitive functioning is still poorly understood.
      The present study was aimed at clarifying the physiological processes underlying
      cerebral and systemic hemodynamics in young hypotensives during cognitive
      engagement. Doppler sonography blood flow velocities in both middle cerebral
      arteries were measured from 17 hypotensives and 15 normotensives during a working
      memory task. Impedance cardiographic and BP measures were also recorded
      continuously. Lower increases in systolic and diastolic BP were observed in
      hypotensives. However, no evidence of lower sympathetic control was found for
      this group, as assessed by pre-ejection period. Flow velocity in middle cerebral
      arteries showed a lower increase in hypotensives throughout the task. Moreover,
      significant positive correlations between BP changes and blood flow velocities in
      middle cerebral arteries during the task were obtained for this group only,
      suggesting a less effective cerebral autoregulation. No difference was found
      between groups in task performance. Results suggest that during cognitive
      challenge hypotensives show impaired hemodynamic adjustments, both central and
      peripheral. However, such alterations do not directly affect cognitive
      performance, at least under moderate cognitive load.

PMID- 22362083
TI  - Regulatory mechanisms underlying the modulation of GIRK1/GIRK4 heteromeric
      channels by P2Y receptors.
AB  - The muscarinic K(+) channel (I (K,ACh)) is a heterotetramer composed of GIRK1
      (Kir3.1) and GIRK4 (Kir3.4) subunits of a G protein-coupled inwardly rectifying
      channel, and plays an important role in mediating electrical responses to the
      vagal stimulation in the heart. I (K,ACh) displays biphasic changes (activation
      followed by inhibition) through the stimulation of the purinergic P2Y receptors,
      but the regulatory mechanism involved in these modulation of I (K,ACh) by P2Y
      receptors remains to be fully elucidated. Various P2Y receptor subtypes and
      GIRK1/GIRK4 (I (GIRK)) were co-expressed in Chinese hamster ovary cells, and the
      effect of stimulation of P2Y receptor subtypes on I (GIRK) were examined using
      the whole-cell patch-clamp method. Extracellular application of 10 MUM ATP
      induced a transient activation of I (GIRK) through the P2Y(1) receptor, which was
      completely abolished by pretreatment with pertussis toxin. ATP initially caused
      an additive transient increase in ACh-activated I (GIRK) (via M(2) receptor),
      which was followed by subsequent inhibition. This inhibition of I (GIRK) by ATP
      was attenuated by co-expression of regulator of G-protein signaling 2, or
      phosphatidylinositol-4-phosphate-5-kinase, or intracellular phosphatidylinositol
      4,5-bisphosphate loading, but not by the exposure to protein kinase C inhibitors.
      P2Y(4) stimulation also persistently suppressed the ACh-activated I (GIRK). In
      addition, I (GIRK) evoked by the stimulation of the P2Y(4) receptor exhibited a
      transient activation, but that evoked by the stimulation of P2Y(2) or P2Y(12)
      receptor showed a rather persistent activation. These results reveal (1) that
      P2Y(1) and P2Y(4) are primarily coupled to the G(q)-phospholipase C-pathway,
      while being weakly linked to G(i/o), and (2) that P2Y(2) and P2Y(12) involve
      G(i/o) activation.

PMID- 22362084
TI  - Nutritional screening for risk prediction in patients scheduled for abdominal
      operations.
AB  - BACKGROUND: Increased risks related to surgery might reflect the nutritional
      status of some patients. Such a group might benefit from perioperative
      nutritional support. The purpose of this study was to identify the relative
      importance of nutritional risk screening along with established medical,
      anaesthetic and surgical predictors of postoperative morbidity and mortality.
      METHODS: This prospective observational study enrolled consecutive eligible
      patients scheduled for elective abdominal operations. Data were collected on
      nutritional variables (body mass index, weight loss, food intake), age, sex, type
      and extent of operation, underlying disease, American Society of
      Anesthesiologists grade and co-morbidities. A modified composite nutritional
      screening tool (Nutritional Risk Screening, NRS 2002) currently recommended by
      European guidelines was used. Relative complication rates were calculated with
      multiple logistic regression and cumulative proportional odds models. RESULTS:
      Some 653 patients were enrolled of whom 132 (20.2 per cent) sustained one or more
      postoperative complications. The frequency of this event increased significantly
      with a lower food intake before hospital admission. No other individual or
      composite nutritional variable provided comparable or better risk prediction
      (including NRS 2002). Other factors significantly associated with severe
      postoperative complications were ASA grade, male sex, underlying disease, extent
      of surgical procedure and volume of transfused red cell concentrates. CONCLUSION:
      In abdominal surgery, preoperative investigation of feeding habits may be
      sufficient to identify patients at increased risk of complications. Nutritional
      risk alone, however, is not sufficient to predict individual risk of
      complications reliably.

PMID- 22362085
TI  - Antineutrophil cytoplasmic antibodies: two cases of changing antigenic
      specificity.
AB  - The transformation of the antineutrophil cytoplasmic antibody (ANCA) specificity
      in the absence of specific drug treatment has not been reported in the
      literature. A few studies have suggested changes in the epitopes recognized by
      the ANCAs. We describe two patients who switched from myeloperoxidase-positive to
      PR3 (proteinase 3)-positive ANCA during the course of their disease process and
      subsequently remained unchanged. One patient developed ulcerative colitis
      following the appearance of PR3-ANCA while the other remains quiescent. Regular
      follow-up and close monitoring of ANCA specificity are essential. A change of
      specificity may indicate the development of a new ANCA-related disease.

PMID- 22362086
TI  - Twenty-four-hour urinary trace element excretion: reference intervals and
      interpretive issues.
AB  - BACKGROUND: Introduction of inductively coupled plasma mass spectrometry (ICP-MS)
      into clinical laboratories has led to an increasing application of analyses to
      risk assessment for toxicity from environmental exposure to trace elements, and
      in occupational monitoring. Interpretation of results from random urine samples
      may be problematic and measurement of excretion over 24 h is sometimes
      preferable. Recent reference data are sparse. METHODS: Twenty-four-hour urine
      samples from 111 healthy adults from the renal stones clinic in Southampton, UK,
      were analysed for 31 trace elements using ICP-MS and for zinc using atomic
      absorption spectroscopy. Non-parametric 0.95 coverage intervals were determined
      for trace element excretion per 24 h and as a ratio to creatinine, for the full
      study cohort and separately for men (n=77) and women (n=34). RESULTS: Beryllium
      was undetectable in 95% of samples, bismuth in 87% and uranium in 75%. In
      comparison with published ranges, reference intervals for this cohort were higher
      for molybdenum, tin and vanadium, and for arsenic due to inclusion of fish
      arsenicals. Aluminium, chromium, iron, lead and mercury were lower. In our
      cohort, 24-h excretion of 17 elements was significantly higher in men than in
      women. However, when expressed as trace element to creatinine ratios, the
      situation reversed strikingly. Because of their lower creatinine excretion,
      ratios for 18 elements were significantly higher for women. CONCLUSIONS: New
      adult reference intervals were obtained for 24-h urine trace element excretion.
      Trace element:creatinine ratios must be used cautiously, with separate ranges for
      men and women.

PMID- 22362087
TI  - Kinematic factors affecting fast and slow straight and change-of-direction
      acceleration times.
AB  - In many sports, players are often required to accelerate immediately after rapid
      changes of direction (CODs) before performing a subsequent COD movement.
      Therefore, court-based players will often not attain their maximum velocity
      before having to decelerate and change direction. The purpose of this study was
      to determine what kinematic factors affected fast and slow straight acceleration
      (SA) and change-of-direction acceleration (CODA) times. National under-21 netball
      players performed 3 trials each of a 2.5-m SA and a CODA involving a 180 degrees 
      COD followed immediately by a 2.5-m sprint. Players were grouped into either a
      faster or slower category based on performance times (2.5-m time). Significantly
      higher average step frequency (4%, p = 0.03) was observed for the faster group
      when compared with the slower group in the CODA task. For the SA task, faster
      times were associated with significantly smaller average step lengths (SLs; 7%, p
      = 0.03), greater torso angles (i.e., greater forward lean; 30-37%, p < 0.001),
      and smaller hip angle (less knee lift) in the first step (21-22%, p = 0.00). The
      SA task was associated with significantly longer average SLs (21-23%, p = 0.00)
      and significantly longer SL across all 3 steps as compared with the CODA task (17
      27%, p < 0.001) A significantly increased forward lean was associated with the
      first step of the SA task (34%, p < 0.001) and significantly higher knee lift for
      the first and second steps of the SA task (11-22%, p = 0.00 and 0.04,
      respectively). These kinematic differences can be used for training purposes for
      both coaches and strength and conditioning practitioners.

PMID- 22362088
TI  - Effect of grip width on electromyographic activity during the upright row.
AB  - The upright row (URR) is commonly used to develop the deltoid and upper back
      musculature. However, little information exists concerning muscle recruitment
      during variations of this exercise. Sixteen weight-trained men completed 2
      repetitions each in the URR with 3 grip conditions: 50, 100, and 200% of the
      biacromial breadth (BAB). The load was the same for all grip conditions and was
      equal to 85% of the 1RM determined at 100% BAB. Repeated measures analyses of
      variance were used to compare the maximal activity of the anterior deltoid (AD),
      lateral deltoid (LD), posterior deltoid (PD), upper trapezius (UT), middle
      trapezius (MT), and biceps brachii (BB) during the 3 grip widths for eccentric
      and concentric actions. Significant differences (p < 0.05) were noted in
      concentric muscle activity for LD (p < 0.001) and PD (p < 0.001), and in
      eccentric muscle activity for AD (p = 0.023), LD (p < 0.001), UT (p < 0.001), MT
      (p < 0.001), and BB (p = 0.003). Bonferroni post hoc analysis revealed
      significant pairwise differences in the concentric actions from the LD (50% vs.
      200% BAB and 100% vs. 200% BAB) and PD (50% vs. 200% BAB and 100% vs. 200% BAB),
      and eccentric actions of the LD (all comparisons), UT (all comparisons), MT (50%
      vs. 200% BAB and 100% vs. 200% BAB), and BB (50% vs. 200% BAB), with large-to
      very-large effect sizes (ESs). Moderate-to-large ESs were noted for several
      nonsignificant comparisons. The main findings of this investigation are increased
      deltoid and trapezius activity with increasing grip width, and correspondingly
      less BB activity. Therefore, those who seek to maximize involvement of the
      deltoid and trapezius muscles during the URR should use a wide grip.

PMID- 22362090
TI  - Distinct temporal organizations of the strength- and power-training loads produce
      similar performance improvements.
AB  - This study aimed to compare the effects of distinct temporal organizations of
      strength and power training loads on strength, power, and speed improvements.
      Sixty soldiers with at least 1 year in the army volunteered for this study. The
      subjects were divided into 4 groups: control group (CG: n = 15; age: 20.18 +/-
      0.72 years; height: 1.74 +/- 0.06 m; and weight: 66.7 +/- 9.8 kg); successive
      mesocycle group (SMG: n = 15; age: 20.11 +/- 0.7 years; height: 1.72 +/- 0.045 m;
      and weight: 63.1 +/- 3.6 kg); successive-week group (SWG: n = 15; age: 20.36 +/-
      0.64 years; height: 1.71 +/- 0.05 m; and weight: 66.1 +/- 8.0 kg); and
      simultaneous daily group (SDG: n = 15; age: 20.27 +/- 0.75 years; height: 1.71 +/
      0.068 m; and weight: 64.0 +/- 8.8 kg). In the SMG, heavy resistance training
      (HRT), jump squat exercise (JS), and countermovement jumps (CMJ) were performed
      in successive mesocycles of 3 weeks each. In the SWG, HRT, JS, and CMJ were
      trained in 1-week blocks into 3 mesocycles of 3 weeks each. In the SDG, HRT, JS,
      and CMJ were trained daily in all the 3 mesocycles of 3 weeks each. Total volume
      was equalized between groups. The following dependent variables were analyzed:
      squat 1RM, CMJ height, 20-m sprint speed, mean power, and mean propulsive power
      in the squat exercise (60% of the squat 1RM) and in the JS (45% of the squat
      1RM). Significant improvements for all the dependent variables were detected from
      pretraininig to posttraining in all the training groups (p <= 0.05), without any
      between-group differences. Our data suggest that the temporal organization of the
      training load is not critical for performance improvements in this population.

PMID- 22362089
TI  - Intersegmental moment analysis characterizes the partial correspondence of
      jumping and jerking.
AB  - The aim of this study was to quantify internal joint moments of the lower limb
      during vertical jumping and the weightlifting jerk to improve awareness of the
      control strategies and correspondence between these activities, and to facilitate
      understanding of the likely transfer of training effects. Athletic men completed
      maximal unloaded vertical jumps (n = 12) and explosive push jerks at 40 kg (n =
      9). Kinematic data were collected using optical motion tracking and kinetic data
      via a force plate, both at 200 Hz. Joint moments were calculated using a
      previously described biomechanical model of the right lower limb. Peak moment
      results highlighted that sagittal plane control strategies differed between
      jumping and jerking (p < 0.05) with jerking being a knee dominant task in terms
      of peak moments as opposed to a more balanced knee and hip strategy in jumping
      and landing. Jumping and jerking exhibited proximal to distal joint involvement
      and landing was typically reversed. High variability was seen in nonsagittal
      moments at the hip and knee. Significant correlations were seen between jump
      height and hip and knee moments in jumping (p < 0.05). Although hip and knee
      moments were correlated between jumping and jerking (p < 0.05), joint moments in
      the jerk were not significantly correlated to jump height (p > 0.05) possibly
      indicating a limit to the direct transferability of jerk performance to jumping.
      Ankle joint moments were poorly related to jump performance (p > 0.05). Peak knee
      and hip moment generating capacity are important to vertical jump performance.
      The jerk appears to offer an effective strategy to overload joint moment
      generation in the knee relative to jumping. However, an absence of hip
      involvement would appear to make it a general, rather than specific, training
      modality in relation to jumping.

PMID- 22362091
TI  - The evaluation of a new lower-body reaction time test.
AB  - The purpose of this study was to investigate the reliability of 2 lower-body
      reaction time (RT) tests to determine the differences in RTs between genders and
      compatible and incompatible conditions. Fifteen male and female (N = 30; 22.63 +/
      2.88 years; 175.31 +/- 8.72 cm; 67.33 +/- 9.71 kg) sport science students
      participated in this study. Subjects were required to complete 2 lower-body RT
      tests responding to an arrow during compatible (same direction) and incompatible
      (opposite direction) stimulus-response conditions. The "simple" foot RT test
      required subjects to step quickly on the appropriate mat, as directed by the
      stimulus, with response time being measured. The "complex" foot RT test required
      subjects to leap off a force plate to the appropriate mat in response to the
      stimulus, with RT, movement time (MT), and total movement time (TMT) being
      measured. Intraclass correlation coefficient, coefficient of variation, and
      paired samples t-test (p <= 0.05) were calculated for all variables. High
      reliability was observed for both tests between compatible and incompatible
      conditions. Significant differences (p <= 0.05) were observed between genders for
      RT during the simple RT test. Significant differences (p <= 0.05) were observed
      for MT and TMT during compatible and incompatible conditions for the complex RT
      test. In conclusion, both tests are reliable to determine lower-body RTs during
      both conditions. Movement time and TMT during the complex RT test were
      significantly different, suggesting that MT could be the discriminating factor
      between conditions and also genders. Examining lower-body RTs during a movement
      commonly observed in sports may provide coaches more details about the athletes'
      cognitive and athletic ability, enabling the components of RT to be trained.

PMID- 22362092
TI  - [Pulmonary events induced by non-steroidal anti-inflammatory drugs in patients
      with sickle cell disease].
AB  - Painful sickle cell crises are among the principal manifestations of sickle cell
      disease. Their treatment routinely requires the use of non-steroidal anti
      inflammatory drugs (NSAIDS). These drugs also, however, inhibit the
      cyclooxygenase cycle in arachidonic acid metabolism, promoting the synthesis of
      leukotrienes, which have bronchoconstrictive effects. This study took place from
      March through August, 2007, and included 100 patients of both sexes, aged 2 to 59
      years, with any sickle cell phenotype (SS, SC, AS, SFA2, or SAFA2) and treated by
      NSAIDs in the Immunology and Haematology department of the University Hospital of
      Cocody. We analysed the characteristics of the respiratory events induced by
      taking NSAIDs to identify potential risk factors for their occurrence. We found
      that 5% of these patients presented respiratory symptoms linked to NSAIDs. These
      appeared within 30 minutes of drug intake for 80%; in 60% of these cases, only
      corticosteroid and antihistamine treatment resolved these symptoms. The
      occurrence of respiratory events did not differ by sex; however, younger subjects
      were more exposed to these respiratory events. All patients with family or
      individual history of atopy-like hypersensitivity type I events presented these
      respiratory symptoms when taking NSAIDS for sickle-cell crises.

PMID- 22362094
TI  - Sea urchin TiO2-nanoparticle hybrid composite photoelectrodes for CdS/CdSe/ZnS
      quantum-dot-sensitized solar cells.
AB  - The sea urchin TiO(2) (SU TiO(2)) particles composed of radially aligned rutile
      TiO(2) nanowires are successfully synthesized through the simple solvothermal
      process. SU TiO(2) was incorporated into the TiO(2) nanoparticle (NP) network to
      construct the SU-NP composite film, and applied to the CdS/CdSe/ZnS quantum-dot
      sensitized solar cells (QDSSCs). A conversion efficiency of 4.2% was achieved
      with a short-circuit photocurrent density of 18.2 mA cm(-2) and an open-circuit
      voltage of 531 mV, which corresponds to ~20% improvement as compared with the
      values obtained from the reference cell made of the NP film. We attribute this
      extraordinary result to the light scattering effect and efficient charge
      collection.

PMID- 22362095
TI  - [Prosthetic rehabilitation of a traumatic occlusion due to bulimia nervosa. Case
      report].
AB  - Because of the typical localisation of erosions in anorectic/bulimic patients,
      the dentist is frequently the first medical person to discern this general
      illness (anorexia and bulimia nervosa). From the dental viewpoint, the aim should
      be to preserve sound dental tissue and to prevent further toothwear. A
      restorative treatment is to be carried out only after causal therapy and after
      resolving the basic disease. By means of this procedure a good long-term
      prognosis can be expected. Considering the patient's young age, dentistry should
      be preservative using the adhesive technique. This case report documents the
      systematic procedure of the functional and esthetic rehabilitation of an eroded
      dentition and shows factors essential to the treatment.

PMID- 22362096
TI  - In vivo and in vitro validation of aortic flow quantification by time-resolved
      three-dimensional velocity-encoded MRI.
AB  - Three-dimensional velocity-encoded cine magnetic resonance imaging (3D VEC MRI)
      allows for calculation of secondary flow parameters that may be used to estimate
      prognosis of individual cardiovascular diseases. However, its accuracy has not
      been fully investigated yet. The purpose of this study was to validate aortic
      flow quantification by 3D VEC MRI in vitro and in vivo using stacked two
      dimensional acquisitions. Time-resolved stacks of two-dimensional planes with
      three-directional velocity-encoding (stacked-2D-3dir-MRI) were acquired in an
      elastic tube phantom with pulsatile flow simulating aortic flow as well as in 11
      healthy volunteers (23 +/- 2 years). Previously validated two-dimensional through
      plane VEC MRI at six equidistant levels in vitro and three locations in vivo
      (ascending aorta/aortic arch/descending aorta) was used as reference standard.
      The percentage difference of the stacked-2D-3dir-MRI measurement to the reference
      standard was defined as the parameter for accuracy. For in vitro aortic flow,
      stacked-2D-3dir-MRI underestimated average velocity by -6.8% (p < 0.001),
      overestimated average area by 13.6% (p < 0.001), and underestimated average flow
      by -7.4% (p < 0.001). Accuracy was significantly higher in the field of view
      centre compared to off-centre (p = 0.001). In vivo, stacked-2D-3dir-MRI
      underestimated average velocity (all three locations p < 0.001) and overestimated
      average area at all three locations (p = n.s./<0.001/<0.001). Average flow was
      significantly underestimated in the ascending aorta (p = 0.035), but tended to be
      overestimated in the aortic arch and descending aorta. In conclusion, stacked-2D
      3dir-MRI tends to overestimate average aortic area and to underestimate average
      aortic velocity, resulting in significant underestimation of average flow in the
      ascending aorta.

PMID- 22362097
TI  - Stent strut coverage of titanium-nitride-oxide coated stent compared to
      paclitaxel-eluting stent in acute myocardial infarction: TITAX-OCT study.
AB  - Drug-eluting stents (DES) have reduced the rate of restenosis but recent studies
      have raised concern over the risk of late stent thrombosis (LST). Incomplete
      stent endothelialization and delayed vascular healing have been associated with
      LST. The titanium-nitride-oxide coated bio-active stent (BAS) has shown promising
      results in patients with acute coronary syndromes, but there is little long-term
      optical coherence tomography (OCT) data comparing BAS with DES. The TITAX-AMI
      trial is a prospective, randomized, multicenter trial comparing BAS to paclitaxel
      eluting stent (PES) in 425 patients with acute myocardial infarction. A total of
      18 patients (9 per group) with no major cardiac events during follow-up, were
      enrolled in this substudy >36 months (mean 47 months) after stent implantation.
      Quantitative coronary angiography was performed and stent strut
      endothelialization and vascular healing were assessed with OCT. The binary stent
      strut coverage was significantly higher in the BAS group compared with the PES
      group (99.6 vs. 89.2%, p < 0.001) and there were less malapposed struts in the
      BAS group (0.2 vs. 13.8%, respectively, p < 0.001). The neointimal hyperplasia
      (NIH) thickness (266 +/- 166 vs. 126 MUm +/- 126 MUm, p < 0.001) and percentage
      of NIH area (26.2 vs. 7.6%, p < 0.001) were greater in the BAS group than in the
      PES group. Late incomplete endothelialization was not uncommon after PES
      implantation. Stents in the BAS group were completely endothelialized. This
      difference may contribute to the more common LST after PES implantation in the
      TITAX-AMI trial.

PMID- 22362098
TI  - Microfracture for knee chondral defects: a survey of surgical practice among
      Canadian orthopedic surgeons.
AB  - PURPOSE: The purpose of this study was to describe the practice of microfracture
      surgery for knee chondral defects among Canadian orthopedic surgeons. METHODS:
      All orthopedic surgeon members of the Canadian Orthopaedic Association were
      invited to participate in a survey, designed to explore the microfracture
      technique used by orthopedic surgeons in the treatment for knee chondral defects
      The primary outcome measure was an emailed 26-item questionnaire, which explored
      indications for microfracture surgery, surgical techniques, types of
      postoperative rehabilitation regimes used and assessment of outcome. In addition,
      responses were compared between orthopedic surgeons with a sports medicine
      practice to surgeons with a non-sports medicine practice. RESULTS: The survey
      response rate was 24.6% (299/1,216), with 131 regularly performing microfracture.
      41% of surgeons indicated that they had no upper limit for age at the time of
      surgery, and 87% indicated no upper limit for body mass index. The majority of
      respondents (97%) resected cartilage back to a stable margin, while 69% of
      respondents removed the calcified cartilage layer prior to creating holes. Only
      11% of respondents used continuous passive motion (CPM) postoperatively, and 39%
      did not restrict weight bearing. Sports surgeons were more likely than non-sports
      surgeons to remove the calcified cartilage layer, use a 45 degrees  pick, use CPM
      and restrict weight bearing postoperatively (all P values < 0.05). CONCLUSIONS:
      This survey on microfracture for knee chondral defects revealed widespread
      variation among surgeons regarding the indications for surgery, surgical
      technique, postoperative rehabilitation and assessment of outcome. Sports
      surgeons demonstrate better evidence-based practice than non-sports surgeons for
      a few important parameters. LEVEL OF EVIDENCE: Cross-sectional survey, Level II.

PMID- 22362100
TI  - Moderating supplementary data.

PMID- 22362101
TI  - Dynamic decision making in the brain.
AB  - How do we make decisions? A study uses MEG to provide the spatial as well as the
      temporal resolution needed to answer this question, together with computational
      modeling, which allows for complex non-linear decision models. This work helps
      resolve some of the seemingly contradictory results from previous work.

PMID- 22362099
TI  - Preventive and improvement effects of exercise training and supplement intake in
      white adipose tissues on obesity and lifestyle-related diseases.
AB  - Recent increases in the number of obese individuals and individuals suffering
      from lifestyle-related diseases, such as type 2 diabetes, that accompany obesity
      have become a serious social problem. White adipose tissue (WAT) is more than a
      mere organ for storage of energy; it is also a highly active metabolic and
      endocrine organ that secretes physiologically active substances collectively
      known as adipokines, including tumor necrosis factor-alpha and adiponectin.
      Dysregulated expression of adipokines in WAT that is hypertrophied by obesity has
      been closely associated with the phenomenon of insulin resistance. Therefore, WAT
      is currently considered to be one of the tissues that promote lifestyle-related
      diseases. Reduction of excess WAT that results from obesity is seen as an
      important strategy in preventing and improving lifestyle-related diseases. This
      review shows that exercise training as well as intake of supplements, such as
      polyphenols, is one strategy for this, because this regimen can result in
      reduction of WAT mass, which affects the expression and secretory response of
      adipokines.

PMID- 22362102
TI  - NMDA receptor permeation: a light in the tunnel.
AB  - A single amino acid residue determines single-channel conductance, ion permeation
      and channel block in the NMDA receptor, three of the key features of this ligand
      gated ion channel.

PMID- 22362103
TI  - Cilia: conductors' batons of neuronal maturation.
AB  - The primary cilium, a signal transduction organelle, is present on the cell
      bodies of adult-born dentate gyrus granule cells as they begin maturation. In its
      absence, their maturation and integration are impaired.

PMID- 22362104
TI  - Mapping out hippocampal inhibition.
AB  - A synthesis of opto- and pharmacogenetics is beginning to reveal how various
      interneuron types direct incoming traffic in the hippocampus to help create a map
      of the environment.

PMID- 22362105
TI  - An upstream interacting context based framework for the computational inference
      of microRNA functions.
AB  - With the rapid accumulation of microRNA (miRNAs), a class of newly identified
      small noncoding RNAs, in silico inference of miRNA functions has become one of
      the central tasks in miRNA bioinformatics. Traditional methods have helped in the
      understanding of miRNAs, but they also have limitations. In this paper, we first
      gave a brief review for the progress of bioinformatic methods in miRNA function
      inference and next presented a new framework (miRUPnet) for inferring the
      functions of miRNAs by functional analysis of a novel dimension of miRNA network,
      the context of its transcription factors (TFs) in a protein-protein interaction
      network. This dimension represents specific biological processes initiated by TF
      combinations and therefore differs from traditional methods in concept. To
      validate the accuracy of our method, we first comprehensively mined literature
      reported miRNA functions and then made a comparison with the prediction result.
      The results show that even using the stringent TFBS rule, our method has
      independently predicted 68.2% of the literature reported miRNA functions,
      suggesting that miRUPnet has a high accuracy. Moreover, our approach successfully
      predicted specific functions that could not be inferred for given miRNAs using
      traditional methods. More importantly, it can distinguish miRNAs from the same
      family, as well as those present in multiple copies that cannot be differentiated
      through traditional methods. This study presents a new concept and dimension for
      miRNA function inference. miRUPnet represents an important and novel method for
      inferring the function of miRNAs. miRUPnet is available at
      http://cmbi.bjmu.edu.cn/mirupnet.

PMID- 22362107
TI  - The importance of the energetic species in pulsed laser deposition for
      nanostructuring.
AB  - This work reports on the optical and structural properties of nanostructured
      films formed by Ag nano-objects embedded in amorphous aluminium oxide (a
      Al(2)O(3)) prepared by alternate pulsed laser deposition (PLD). The aim is to
      understand the importance of the energetic species involved in the PLD process
      for nanostructuring, i.e. for organizing nanoparticles (NPs) in layers or for
      self-assembling them into nanocolumns (NCls), all oriented perpendicular to the
      substrate. In order to change the kinetic energy of the species arriving at the
      substrate, we use a background gas during the deposition of the embedding a
      Al(2)O(3) host. It was produced either in vacuum or in a gas pressure (helium and
      argon) while the metal NPs were always produced in vacuum. The formation of NPs
      or NCls is easily identified through the features of the surface plasmon
      resonances (SPR) in the extinction spectra and confirmed by electron microscopy.
      The results show that both the layer organization and self-assembling of the
      metal are prevented when the host is produced in a gas pressure. This result is
      discussed in terms of the deceleration of species arriving at the substrate in
      gas that reduces the metal sputtering by host species (by ~58%) as well as the
      density of the host material (by >=19%). These reductions promote the formation
      of large voids along which the metal easily diffuses, thus preventing
      organization and self-organisation, as well as an enhancement of the amount of
      metal that is deposited.

PMID- 22362108
TI  - Radiographic evaluation of segmental motion of scoliotic wedging segment in
      degenerative lumbar scoliosis.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: To evaluate the segmental
      instability of wedging segments using dynamic films and the impact of osteophyte
      formation on segmental motion in degenerative lumbar scoliosis (DLS). SUMMARY OF
      BACKGROUND DATA: Evaluation of segmental instability in DLS is essential for
      spinal surgery to make the decision "fusion or not fusion." Some previous studies
      have shown radiographic data regarding segmental instability in DLS. However,
      little is known about segmental motion of wedging segments in DLS. METHODS: A
      total of 101 patients complaining of neurogenic claudication owing to lumbar
      spinal canal stenosis (LCS) were enrolled and divided into 2 groups based on
      their coronal spinal deformity; Cobb angle of >10 degree (DLS group) or <10
      degree (LCS group). The following parameters were measured on anteroposterior
      films: lateral translation, degree of osteophyte formation, and range of motion
      (ROM) in lateral bending films. The facet joint space discrepancy was measured on
      computed tomography images. The radiographic parameters were compared between 85
      wedging segments (>5 degrees) in DLS group and 150 nonwedging segments in LCS
      group. RESULTS: Mean lateral translation was significantly greater in the DLS
      group (P<0.01 for each level). Average joint space discrepancy was significantly
      greater in the DLS group (P<0.01 at L2/3 and L3/4, P =0.01 at L4/5). ROM was
      significantly greater in the DLS group with the same degree osteophyte formation.
      Degree of osteophyte formation was inversely correlated with ROM in the DLS group
      (R(2)=0.5696). CONCLUSIONS: The present study indicated that wedging segments in
      DLS had greater motion than nonwedging segments in LCS. However, the osteophyte
      formation provided restabilization for the wedging segments in DLS, suggesting
      that evaluation of osteophyte formation is an important factor in surgical
      decision making for DLS.

PMID- 22362106
TI  - Catalytic enantioselective synthesis of beta-trifluoromethyl pyrrolines.
AB  - Enantioselective synthesis of beta-trifluoromethylated pyrrolines has been
      developed by the organocatalyzed-conjugated addition of nitromethane to beta
      trifluoromethylated enones, followed by a nitro-reduction/cyclization/dehydration
      sequence in a one-pot procedure with 97-98% ees.

PMID- 22362109
TI  - The position of the aorta relative to the spine for pedicle screw placement in
      the correction of idiopathic scoliosis.
AB  - STUDY DESIGN: An analysis of computed tomography (CT) images of patients with
      adolescent thoracic idiopathic scoliosis for posterior pedicle screw placement.
      OBJECTIVE: To evaluate the relative position of the aorta to the spine by the
      axial CT scans in patients with right thoracic idiopathic scoliosis, and to
      discuss the safe trajectory and screw length for posterior pedicle screw
      placement. SUMMARY OF BACKGROUND DATA: Posterior pedicle screw instrumentation
      and fusion are widely used in the correction of scoliosis. Pedicle screw
      placement in the thoracic spine implies risk of injuring the aorta. Literatures
      on the relative position of the aorta to the spine are mostly focused on the
      anterior surgery. However, few are reported about the posterior surgery. METHODS:
      A total of 47 patients with adolescent right thoracic idiopathic scoliosis who
      underwent CT scan of total spine before surgery were included in this study.
      Transverse plane including bilateral pedicles, lamina, and transverse process was
      selected for measurement from T4 to T12. We defined a new coordinate system, and
      5 parameters were measured in each vertebral body from T4 to T12 of the patients.
      The point where the left pedicle axial line and the base of the left transverse
      process intersected was defined as the origin of the coordinate system. A line
      connecting bilateral intersection was defined as x-axis. y-axis perpendicular to
      the x-axis is drawn ventrally from the origin. The left pedicle-aorta angle
      (alpha), the left aorta angle (beta), the left pedicle-aorta distance (PAD), the
      aorta-x-axis distance (AXD), and the vertebral rotation angle (gamma) were
      measured. RESULTS: The values of angles alpha and beta had a tendency of first
      increasing and then decreasing, and increasing again from T4 to T12. The lowest
      value of angle alpha occurred at T10 (7.45+/-6.10 degrees), followed by T4
      (8.89+/-6.49 degrees), T11 (9.13+/-7.59 degrees), and T9 (9.74+/-6.11 degrees).
      PAD and AXD values had a tendency of decreasing first and then increasing from T4
      to T12. The lowest values of PAD and AXD occurred at T6; 25.94+/-5.33 and 23.64+/
      6.53 mm, respectively. From the cephalad to the caudal spine, angle gamma
      increased first and then decreased. The highest value occurred at T7 (2.32+/-6.83
      degrees), which rotated to the right side. The second largest value occurred at
      T8 (2.23+/-7.76 degrees). Statistical analysis indicated that the apical
      vertebral translation and vertebral rotation angle were significantly positively
      correlated to angles alpha and beta (P<0.05). CONCLUSIONS: The highest risk of
      injuring the aorta when placing pedicle screw during posterior scoliosis surgery
      was at T10, followed by T4, T11, and T9 in right thoracic idiopathic scoliosis.
      Taking a spine CT scan and evaluating the relative position of the aorta to the
      thoracic spine before surgery are significant in precise and safe pedicle screw
      placement.

PMID- 22362110
TI  - Correlation of slipped capital femoral epiphysis with disk degeneration.
AB  - SUMMARY OF BACKGROUND DATA: Spinal osteoarthritis is greater in patients with
      known hip pathology secondary to alterations in spinopelvic geometry. To our
      knowledge, no study has investigated the long-term impact of slipped capital
      femoral epiphysis (SCFE) on the spine. OBJECTIVE: To evaluate the relationship
      between SCFE and the presence of degenerative disk disease and facet arthrosis.
      STUDY DESIGN: An anatomic study of disk degeneration in cadaveric lumbar spines
      with SCFE. METHODS: An observational study was performed on 25 cadaveric
      specimens with SCFE and 647 controls that were identified out of 3100 total
      cadaveric specimens in an osteological collection. The specimens were evaluated
      for disk degeneration and facet arthrosis at L1/2 to L5/S1 using the
      classification of Eubanks and colleagues. Linear regression analyses were then
      used to determine the relationship between SCFE and lumbar disk and facet
      degeneration at each level, correcting for confounding factors such as age, sex,
      and race. RESULTS: Linear regression demonstrated a significant association
      (P<0.01) that was found between SCFE and degenerative disk disease at all levels
      from L1/2 to L5/S1. In addition, a significant association (P<0.01) was found
      between SCFE and facet arthrosis at all levels from L1/2 to L5/S1. CONCLUSIONS:
      The findings of this study show a relationship between SCFE and lumbar disk
      degeneration and facet arthrosis. This relationship may prove useful in
      predicting the course of spinal osteoarthritis in patients with SCFE.

PMID- 22362111
TI  - Would an anatomically shaped lumbar interbody cage provide better stability? An
      in vitro cadaveric biomechanical evaluation.
AB  - STUDY DESIGN: A biomechanical cadaveric study of lumbar spine segments.
      OBJECTIVE: To compare the immediate stability provided by parallel-shaped and
      anatomically shaped carbon fiber interbody fusion I/F cages in posterior lumbar
      interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF)
      constructs with posterior pedicle screw instrumentation. SUMMARY OF BACKGROUND
      DATA: Few biomechanical data are available on the anatomically shaped cages in
      PLIF and TLIF constructs. METHODS: Twenty human lumbar segments were tested in
      flexion-extension (FE) (8 N m flexion, 6 N m extension), lateral bending (LB) (+/
      6 N m), and torsional loading (+/- 5 N m). Each segment was tested in the intact
      state and after insertion of interbody cages in one of 3 constructs: PLIF with 2
      parallel-shaped or anatomically shaped cages and TLIF with 1 anatomically shaped
      cage. All cages received supplementary pedicle screw fixation. The range-of
      motion (ROM) values after cage insertion and posterior fixation were compared
      with the intact specimen values using analysis of variance and multiple
      comparisons with Bonferroni correction. RESULTS: All constructs significantly
      reduced segmental motion relative to intact (P < 0.001). The motion reductions in
      FE, LB, and axial rotation were 85 +/- 15%, 83 +/- 18%, and 67 +/- 6.8% for the
      PLIF construct using parallel cages, 79 +/- 5.5%, 87 +/- 10%, and 66 +/- 20% for
      PLIF using anatomically shaped cages, and 90 +/- 6.8%, 87 +/- 12%, and 77 +/- 22%
      for TLIF with an anatomically shaped cage. In FE and LB, the reductions in the
      ROM caused between the 3 constructs were equivalent (P > 0.05). In axial
      rotation, the TLIF cage provided significantly greater limitation in the ROM
      compared with the parallel-shaped PLIF cage (P = 0.01). CONCLUSIONS: The parallel
      shaped and anatomically shaped I/F cages provided similar stability in a PLIF
      construct. The greater stability of the TLIF construct was likely due to a more
      anterior placement of the TLIF cage and preservation of the contralateral facet
      joint.

PMID- 22362112
TI  - Optimizing the effectiveness of a mechanical suture-based anulus fibrosus repair
      construct in an acute failure laboratory simulation.
AB  - STUDY DESIGN: In vitro comparative, laboratory experiments. OBJECTIVE: This study
      developed a laboratory apparatus that measured resistance to failure using
      pressures similar to intradiscal pressure of a lumbar spinal disk. Various
      combinations of an anular repair device were compared. SUMMARY OF BACKGROUND
      CONTEXT: Herniated material of the intervertebral disk is removed during a lumbar
      discectomy; however, the defect in the anulus fibrosus remains and can provide a
      pathway for future herniation. Repairing the anulus fibrosus could mitigate this
      reherniation and improve patient outcomes. METHODS: A pneumatic cylinder was used
      to increase the pressure of a sealed chamber until artificial nucleus pulposus
      material was expulsed through either a 3-mm circular (diameter) or a 6-mm slit
      anular defect created in a surrogate anulus fibrosus. Each unrepaired condition
      was compared with 3 repaired conditions using a commercially available soft
      tissue repair system. The repaired conditions included: (1) a single tension
      band; (2) 2 tension bands in a cruciate pattern; or (3) 2 tension bands in a
      parallel pattern. Maximum pressure at the point of extrusion of the internal
      chamber material and failure or nonfailure of the repair was measured. RESULTS:
      Significant differences were detected (P<0.05) in maximum failure pressures for
      the nonrepaired (control) versus repaired conditions. With 1 or 2 tension bands
      repairing the circular defect, the maximum failure pressure increased by
      approximately 76% and 131%, respectively. In addition, the failure pressure for 2
      tension bands in either a cruciate or parallel configuration was not different,
      and was approximately 32% higher (P<0.05) than a single tension band in the case
      of the circular defect. Similar results were seen for the slit defect, with the
      exception that no difference between the repaired conditions (ie, single vs. 2
      tension bands) was detected. CONCLUSIONS: This laboratory simulation demonstrated
      that repairing the anulus fibrosus after a discectomy procedure can be beneficial
      for retaining intradiscal material. The use of 2 tension bands, versus a single
      tension band, in either a cruciate or parallel configuration may further improve
      the ability to retain disk material.

PMID- 22362113
TI  - How the NHS measures up to other health systems.

PMID- 22362114
TI  - Managing retinal vein occlusion.

PMID- 22362115
TI  - Incidence of diabetic retinopathy in people with type 2 diabetes mellitus
      attending the Diabetic Retinopathy Screening Service for Wales: retrospective
      analysis.
AB  - OBJECTIVES: To determine the incidence of any and referable diabetic retinopathy
      in people with type 2 diabetes mellitus attending an annual screening service for
      retinopathy and whose first screening episode indicated no evidence of
      retinopathy. DESIGN: Retrospective four year analysis. SETTING: Screenings at the
      community based Diabetic Retinopathy Screening Service for Wales, United Kingdom.
      PARTICIPANTS: 57,199 people with type 2 diabetes mellitus, who were diagnosed at
      age 30 years or older and who had no evidence of diabetic retinopathy at their
      first screening event between 2005 and 2009. 49,763 (87%) had at least one
      further screening event within the study period and were included in the
      analysis. MAIN OUTCOME MEASURES: Annual incidence and cumulative incidence after
      four years of any and referable diabetic retinopathy. Relations between available
      putative risk factors and the onset and progression of retinopathy. RESULTS:
      Cumulative incidence of any and referable retinopathy at four years was 360.27
      and 11.64 per 1000 people, respectively. From the first to fourth year, the
      annual incidence of any retinopathy fell from 124.94 to 66.59 per 1000 people,
      compared with referable retinopathy, which increased slightly from 2.02 to 3.54
      per 1000 people. Incidence of referable retinopathy was independently associated
      with known duration of diabetes, age at diagnosis, and use of insulin treatment.
      For participants needing insulin treatment with a duration of diabetes of 10
      years or more, cumulative incidence of referable retinopathy at one and four
      years was 9.61 and 30.99 per 1000 people, respectively. CONCLUSIONS: Our analysis
      supports the extension of the screening interval for people with type 2 diabetes
      mellitus beyond the currently recommended 12 months, with the possible exception
      of those with diabetes duration of 10 years or more and on insulin treatment.

PMID- 22362116
TI  - Gender differences in behavioral changes elicited by prenatal methamphetamine
      exposure and application of the same drug in adulthood.
AB  - The aim of the present study was to compare the response to sub-chronic
      application of methamphetamine (MA) in adulthood in male and female rats
      prenatally exposed to the same drug. The spontaneous locomotor activity and
      exploratory behavior of adult male and female rats prenatally exposed to 5 mg/kg
      MA or saline (SAL) were tested in a Laboras apparatus (Metris B.V., Netherlands)
      for five consecutive days, 1 hr daily. MA 1 mg/kg or SAL were used as a challenge
      prior to testing. Our results showed that rats prenatally exposed to MA were more
      sensitive to sub-chronic administration of MA in adulthood than prenatally SAL
      exposed rats. However, this sensitizing effect of prenatal MA exposure was
      manifested differently in males and females. In contrast, prenatal MA exposure
      decreased baseline locomotion in females. This study indicates that gender plays
      an important role in the sensitivity to MA during prenatal development and in
      adulthood.

PMID- 22362117
TI  - Effects of interleukin-6 on extravillous trophoblast invasion in early human
      pregnancy.
AB  - Invasion of uterine tissues by extravillous trophoblast cells (EVT) is essential
      for successful human pregnancy. EVT invasion is tightly regulated by a number of
      factors, including growth factors and cytokines, but the mechanisms that underlie
      their regulatory effect remain poorly understood. Interleukin (IL)-6 has been
      suggested to play a role in controlling EVT invasion. We hypothesized that IL-6
      produced by cells in uterine decidua would regulate EVT invasiveness via IL
      6Ralpha and gp130 receptors expressed by trophoblast cells. The effect of IL-6 on
      EVT signalling and cytokine production was also studied. Supernatants from
      disaggregated 'total' decidual cells, CD8(+) T cells, CD10(+) decidual stromal
      cells, CD14 macrophages, CD56(+) uterine natural killer cells, cytotrophoblast
      and EVT cells contained large quantities of IL-6 protein at both 8-10 and 12-14
      weeks gestational age. IL-6Ralpha and gp130 were immunolocalized to EVT in
      placental bed biopsies from 8 to 20 weeks gestation and IL-6Ralpha expression was
      confirmed by western blotting. IL-6 had no effect on the invasive potential of
      EVT from chorionic villi or the immortalized EVT cell line HTR-8/SVneo in a
      Matrigel((r)) invasion assay. IL-6 stimulated phosphorylation of several cell
      signalling proteins in EVT (8-14 weeks' gestation), although significance was
      lost after correction for multiple comparisons. Incubation with IL-6 decreased
      secretion of regulated upon activation, normal T-cell expressed and secreted
      (RANTES) by EVT cells. In conclusion, although IL-6 did not affect trophoblast
      cell invasion, it stimulated EVT cellular cascades and inhibited secretion of
      RANTES involved in a number of cellular processes.

PMID- 22362119
TI  - Sezary syndrome: infiltration of the gastric wall--does it matter?

PMID- 22362120
TI  - Nitric oxide metabolites and arginase I levels in beta-thalassemic patients: an
      Egyptian study.
AB  - Stored red blood cells become deficient in nitric oxide that limits their ability
      to transfer oxygen to tissues that need it. The aims of this study are to assess
      the endogenous nitric oxide metabolites (NOx) and arginase I levels in
      transfusion-dependent beta-thalassemic patients; to compare these levels in
      patients transfused with fresh RBCs with patients transfused with old RBCs, beta
      thalassemic minor patients, and normal control; and to correlate these levels
      with some clinical variables. Group I was composed of 23 patients with homozygous
      beta-thalassemia on hypertransfusion regimen. They were adequately transfused
      with fresh RBC. Group II was composed of 17 patients with homozygous beta
      thalassemia on hypertransfusion regimen. They were adequately transfused with old
      RBCs. Group III was composed of 30 patients with homozygous beta-thalassemia.
      They were adequately transfused with fresh RBCs. Group IV was composed of 18
      patients with homozygous beta-thalassemia. They were adequately transfused with
      old RBCs. Both group III and group IV were supposed to be on hypertransfusion
      regimen, but they did not follow the regimen. Group V was composed of 21 patients
      of beta-thalassemia minor. Nineteen apparently healthy individuals (HbAA) served
      as a control group (group VI). In addition to routine laboratory investigations,
      plasma levels of NOx and serum levels of arginase I were assessed in all
      subjects. The mean values of plasma NOx were significantly decreased in groups
      III and IV compared to the other groups. Also, the levels of NOx were
      significantly decreased in patients who received old RBCs compared to the other
      groups. There were high serum levels of arginase I in groups III and IV compared
      to the other groups. There were significant negative correlations between plasma
      NOx and some hemolytic biochemical markers in groups III and IV. There were
      significant positive correlations between serum arginase I and some hemolytic
      biochemical markers in groups III and IV. Also, there was a significant negative
      correlation between plasma NOx and serum arginase I levels in groups III and IV.
      In non-adequately transfused patients with beta-thalassemia major, inactivation
      of NO correlates with hemolytic rate and is associated with the erythrocyte
      release of cell-free hemoglobin, which consumes NO directly, and the simultaneous
      release of the arginine-metabolizing enzyme arginase, which limits
      bioavailability of the NO synthase substrate, arginine, during the process of
      hemolysis. New treatments aimed at improving arginine and NO bioavailability
      through arginase inhibition, suppression of hemolytic rate, oral arginine
      supplementation, predonation testing, and transfusion of fresh RBCs or use of NO
      donors represent potential therapeutic strategies for this common hemolytic
      disorder.

PMID- 22362121
TI  - The prognostic role of hemochromatosis H63D allele in allogeneic hematopoietic
      stem cell transplantation.
AB  - Iron overload is considered as a significant cause of morbidity and mortality in
      hematopoietic stem cell transplant (HSCT) recipients. The presence of
      hemochromatosis gene (HFE) mutations might exacerbate iron toxicity in the post
      transplant setting. This prospective study was planned to evaluate the genetic
      spectrum of HFE mutations in Turkish patients undergoing HSCT and the impact of
      HFE genotype on transplant morbidity and mortality. HFE genotypes of 102 patients
      [median age, 27.5 years (16-64 years); male/female, 73:29], who underwent
      allogeneic HSCT, were analyzed. Twenty-two patients were heterozygous and 1
      patient was homozygous for the H63D mutation, while the C282Y mutation was
      observed in none of our patients. The frequency of invasive fungal infections
      (IFI) was significantly higher in H63D-mutated patients (p=0.004). H63D mutation
      was identified as an independent risk factor for the development of IFI (p=0.006,
      OR=0.554, SE=0.208), without an impact on overall survival and transplant-related
      mortality. The multifactorial iron-overloaded state in HSCT recipients might
      affect the phenotypic expression of HFE mutations and alter the severity of
      clinical presentation. The impact of HFE genotype on iron parameters and
      transplant-related morbidity and mortality should be validated with further
      studies.

PMID- 22362118
TI  - Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia:
      independent favorable prognostic factor within NPM1 mutated patients.
AB  - We and others have shown that cytogenetically normal (CN)-AML patients with
      biallelic CEBPA gene mutations (biCEBPA) represent a molecularly distinct group
      with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation
      (moCEBPA), however, show no different outcome compared to patients with wildtype
      CEBPA, and these mutations are frequently associated with mutated NPM1 or FLT3
      ITD. So far, no molecular or clinical hallmark has been identified to
      prognostically distinguish moCEBPA patients from patients with wildtype CEBPA.
      Therefore, we used the data of 663 CN-AML patients treated within the AMLCG 1999
      trial to explore the prognostic value of moCEBPA in the context of concomitant
      clinical and molecular markers (mutated NPM1, FLT3-ITD). Multiple Cox regression
      in 515 patients adjusting for all available potential confounders revealed that
      the NPM1 mutation modified the prognostic value of moCEBPA with respect to
      overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011).
      MoCEBPA was beneficial in NPM1 mutated patients: adjusted OS-hazard ratio (HR)
      0.09, 95% confidence interval (CI) 0.01-0.63, p = 0.016; EFS-HR (95% CI) 0.16
      (0.04-0.65), p = 0.010. In contrast, moCEBPA had no prognostic impact in patients
      with wildtype NPM1: OS-HR (95% CI) 1.08 (0.59-1.97), p = 0.804; EFS-HR (95% CI)
      1.12 (0.64-1.96), p = 0.682. We found no prognostic effect modification for
      moCEBPA by FLT3-ITD. The presence of a moCEBPA mutation was shown to be
      associated with prolonged survival in NPM1 mutated CN-AML patients. Confirmation
      of these results in larger studies will clarify whether an additional moCEBPA
      mutation influences the risk stratification of patients with an NPM1 mutated/FLT3
      ITD positive genotype.

PMID- 22362122
TI  - Phase II prospective study of treosulfan-based reduced-intensity conditioning in
      allogeneic HSCT for hematological malignancies from 10/10 HLA-identical unrelated
      donor.
AB  - Different RIC regimens were evaluated prior to allo-HSCT in different
      hematological malignancies. We conducted this prospective study in adult patients
      with various hematological malignancies in order to evaluate the toxicity and
      efficacy of treosulfan-based conditioning, followed by allo-HSCT from 10/10 HLA
      identical unrelated donors. Conditioning included treosulfan 12 g/m(2)/day i.v.
      (day -6 to day -4), fludarabine 30 mg/m(2)/day i.v. (day -6 to day -2), and ATG
      2.5 mg/kg/day (day -2 to day -1). PBSC were used as HSC source. We included 56
      patients (29 AML, 9 MM, 8 MDS, 6 CLL, 3 ALL, and 1 CML) with a median age of 57
      years (18-65.5). Fifty-four (96%) patients engrafted; the cumulative incidence of
      aGVHD grade >=II at 3 months reached 31%. The cumulative incidence of cGVHD at 18
      months was 34% limited and 8% extensive. The median overall survival (OS) was not
      reached with a 3-year probability of 52%. The cumulative incidence of relapse at
      3 years was 25%, and the cumulative incidence of transplant-related mortality
      (TRM) at 12 and 24 months was 20% and 23%, respectively. Treosulfan appears to be
      a good alternative for conditioning of MUD transplant patients with promising
      results in terms of OS, relapse, and TRM.

PMID- 22362123
TI  - Extramedullary myeloma relapses.

PMID- 22362124
TI  - Prenatal diagnosis of abnormal course of umbilical vein and ductus venosus
      agenesis: report of three cases.
AB  - Ductus venosus connecting the portal and embryonic venous circulation into the
      inferior vena cava has a crucial role in fetal circulation. The absence of ductus
      venosus is a rare anomaly, in which the umbilical vein connection to the venous
      system may be extrahepatic, bypassing the liver or intrahepatic via the portal
      venous system. We report three cases of ductus venosus agenesis with associated
      anomalies. In two of them the connection was directly to the right atrium,
      whereas the umbilical vein drained to the left internal iliac artery in the third
      case.

PMID- 22362125
TI  - Left pleural effusion and fever of unknown origin--a clue to thoracic arterial
      pathology.
AB  - The subset of patients who have both fever of unknown origin (FUO) and a
      nondiagnostic pleural effusion on presentation has not been previously
      investigated. A retrospective search of all patients classified as 'classic' FUO
      one week after admission to a department of general internal medicine identified
      71 patients over 15 years. Seven were found to have associated pleural
      effusion(s) on admission (9.8%). In three patients thoracic large vessel
      pathology was diagnosed (chronic aortic dissection, giant cell arteritis and
      Takayasu arteritis). In these patients, the pleural effusion was predominantly
      left-sided, small to moderate in amount and nondiagnostic on thoracentesis. The
      effusions resolved spontaneously or with appropriate treatment. Thus, in patients
      with prolonged fever and systemic symptoms, a 'bland' left-sided pleural effusion
      may be a diagnostic clue to underlying inflammation of large thoracic arteries.
      Pleural irritation due to its anatomical proximity to the large arteries on the
      left side of the thorax may underlie the pathogenesis. Recognition of this sign
      may lead to a more timely diagnosis of occult thoracic large vessel pathology.

PMID- 22362126
TI  - Toxic encephalopathy.

PMID- 22362127
TI  - Concurrent validity of single-item measures of emotional exhaustion and
      depersonalization in burnout assessment.
AB  - BACKGROUND: Burnout is a common problem among physicians and physicians-in
      training. The Maslach Burnout Inventory (MBI) is the gold standard for burnout
      assessment, but the length of this well-validated 22-item instrument can limit
      its feasibility for survey research. OBJECTIVE: To evaluate the concurrent
      validity of two questions relative to the full MBI for measuring the association
      of burnout with published outcomes. DESIGN, PARTICIPANTS, AND MAIN MEASURES: The
      single questions "I feel burned out from my work" and "I have become more callous
      toward people since I took this job," representing the emotional exhaustion and
      depersonalization domains of burnout, respectively, were evaluated in published
      studies of medical students, internal medicine residents, and practicing
      surgeons. We compared predictive models for the association of each question,
      versus the full MBI, using longitudinal data on burnout and suicidality from 2006
      and 2007 for 858 medical students at five United States medical schools, cross
      sectional data on burnout and serious thoughts of dropping out of medical school
      from 2007 for 2222 medical students at seven United States medical schools, and
      cross-sectional data on burnout and unprofessional attitudes and behaviors from
      2009 for 2566 medical students at seven United States medical schools. We also
      assessed results for longitudinal data on burnout and perceived major medical
      errors from 2003 to 2009 for 321 Mayo Clinic Rochester internal medicine
      residents and cross-sectional data on burnout and both perceived major medical
      errors and suicidality from 2008 for 7,905 respondents to a national survey of
      members of the American College of Surgeons. KEY RESULTS: Point estimates of
      effect for models based on the single-item measures were uniformly consistent
      with those reported for models based on the full MBI. The single-item measures of
      emotional exhaustion and depersonalization exhibited strong associations with
      each published outcome (all p <= 0.008). No conclusion regarding the relationship
      between burnout and any outcome variable was altered by the use of the single
      item measures rather than the full MBI. CONCLUSIONS: Relative to the full MBI,
      single-item measures of emotional exhaustion and depersonalization exhibit strong
      and consistent associations with key outcomes in medical students, internal
      medicine residents, and practicing surgeons.

PMID- 22362128
TI  - Externalizing psychopathology and persistence of offending in childhood first
      time arrestees.
AB  - This study aims to investigate the predictive validity of externalizing
      psychopathology for persistence in delinquent behavior when controlling for socio
      demographic and first arrest characteristics in childhood first-time arrestees. A
      sample of first-time arrestees aged under 12 (n = 192) was assessed using the
      Diagnostic Interview Schedule for Children (DISC-IV) parent-version on attention
      deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and
      conduct disorder (CD). Based on child and parent reports of offending as obtained
      at arrest and at 2-year follow-up, three groups of offenders were differentiated:
      (1) persistent high (n = 48), (2) occasional (n = 62), and (3) persistent low
      offenders (n = 82). Over one-third of the sample (33.9%) was diagnosed with an
      externalizing disorder, and 13.5% with both ADHD and ODD or CD. Higher levels of
      externalizing psychopathology distinguished persistent high offenders from
      occasional (comorbid ADHD and ODD/CD: OR 8.2, CI 2.6-25.5) and persistent low
      offenders (comorbid ADHD and ODD/CD: OR 18.2, CI 4.6-72.3; ADHD: OR 4.1, CI 1.3
      13.0), over and above socio-demographic and first offense characteristics. Living
      with both biological parents distinguished the persistent low offenders from the
      occasional offenders (OR 2.5, CI 1.2-5.0). Since the prevalence of externalizing
      disorders was high and predicted re-offending, mental health screening and
      intervention initiatives, aiming at these conditions, should be investigated for
      this high-risk sample.

PMID- 22362130
TI  - Long-distance energy transfer photosensitizers arising in hybrid nanoparticles
      leading to fluorescence emission and singlet oxygen luminescence quenching.
AB  - This paper presents energy transfer occurring in small organically modified core
      shell nanoparticles (core lanthanide oxide, shell polysiloxane) (diameter < 10
      nm) conjugated with photosensitizers designed for photodynamic therapy
      applications. These nanoparticles covalently encapsulate a photosensitizing PDT
      drug in different concentrations. Stable dispersions of the nanoparticles were
      prepared and the photophysical properties of the photosensitizers were studied
      and compared to those of the photosensitizers in solution. Increasing the
      photosensitizer concentration in the nanoparticles was not found to cause any
      changes in the absorption properties while fluorescence and singlet oxygen
      quantum yields decreased. As a possible explanation, we have suggested that both
      long distance energy transfer such as FRET and self-quenching could occur into
      the nanoparticles. A simple "trend" model of this kind of energy transfer
      complies with results of experiments on steady state fluorescence and singlet
      oxygen luminescence. 

PMID- 22362131
TI  - Clinical and laboratory features of myelofibrosis and limitations of current
      therapies.
AB  - Myelofibrosis (MF) is a life-threatening clonal stem cell malignancy
      characterized by progressive bone marrow fibrosis and ineffective hematopoiesis.
      The term "MF" encompasses primary myelofibrosis (PMF) as well as 2 other
      phenotypically similar malignancies: post-polycythemia vera (PV) MF (PPV-MF) and
      post-essential thrombocythemia (ET) MF (PET-MF). The World Health Organization
      classification system for myeloid malignancies recognizes PMF, PV, ET, and
      chronic myeloid leukemia (CML) as the "classic" myeloproliferative neoplasms
      (MPNs). Patients with low- or intermediate-1-risk disease have a median survival
      of 6-15 years, in contrast to those with intermediate-2- or high-risk disease,
      which is associated with a considerably worse prognosis. Following transformation
      into (secondary) acute myeloid leukemia (AML), the prognosis of MF is even worse,
      with a median survival of 3 months or less. Due to the heterogeneous nature of
      MF, the diagnosis and treatment of this malignancy can be challenging. At
      present, the only treatment that can be applied with curative intent is
      allogeneic stem cell transplantation (SCT), whereas no other specific therapies
      exist that are approved by the US Food and Drug Administration (FDA) for MF.
      Since most patients with MF appear not to be eligible for allogeneic SCT,
      patients are often treated by conventional "older" drugs such as androgens and
      hydroxyurea (HU; hydroxycarbamide), with the principal objective being
      palliation. Following the establishment of a causal role of a specific mutation
      in the Janus kinase type 2 (JAK2) gene, namely JAK2V617F, in the molecular
      pathogenesis of MPNs in 2005, many efforts have been directed towards the
      development of novel JAK2 (including JAK1/JAK2) inhibitors. Other investigative
      approaches include immunomodulatory agents, histone deacetylase inhibitors,
      hedgehog inhibitors, and others. Recently, the positive results of the first in
      class of the JAK1/JAK2 inhibitors, ruxolitinib (formerly INCB18242), from 2 large
      phase III studies were presented and are discussed herein.

PMID- 22362129
TI  - Inhibition of p38 MAPK reduces expression of vascular endothelial growth factor
      in allergic airway disease.
AB  - BACKGROUND: The p38 mitogen-activated protein kinase (MAPK) appears to play an
      important role in various pathophysiological responses and has been suggested to
      be involved in many processes considered critical to the inflammatory response
      and tissue remodeling. Bronchial asthma is a chronic inflammatory disorder of the
      airway accompanied by increased vascular permeability. Vascular endothelial
      growth factor (VEGF) is a potent stimulator of bronchial inflammation, airway
      remodeling, and physiologic dysregulation that augments antigen sensitization and
      T-helper type 2 cell (Th2)-mediated inflammation in allergic airway diseases.
      However, there are little data on the relationship between p38 MAPK signaling and
      VEGF expression in allergic airway disease. OBJECTIVE: This study aimed to
      investigate the role of p38 MAPK on the pathogenesis of allergic airway disease,
      more specifically in VEGF expression. METHODS: Using ovalbumin (OVA)-inhaled mice
      and a selective p38 MAPK inhibitor, SB 239063, the involvement of p38 MAPK in
      allergen-induced VEGF expression in the airway was evaluated. RESULTS: The
      increases of phosphorylation of p38 MAPK, VEGF protein expression, and vascular
      permeability in the lung after OVA inhalation were decreased substantially by the
      administration of SB 239063. In addition, SB 239063 significantly reduced the
      increase of Th2 cytokines and OVA-specific IgE. The inhibition of p38 MAPK or
      VEGF signaling prevented and also decreased the increases in the number of
      inflammatory cells and airway hyperresponsiveness in OVA-induced allergic airway
      disease. CONCLUSIONS: These results indicate that inhibition of p38 MAPK may
      attenuate allergen-induced airway inflammation and vascular leakage through
      modulation of VEGF expression in mice.

PMID- 22362132
TI  - Crystal structure of a dimeric Ser49- PLA2-like myotoxic component of the Vipera
      ammodytes meridionalis venomics reveals determinants of myotoxicity and membrane
      damaging activity.
AB  - Myotoxicity and membrane damage play a central role in the life-threatening
      effects of the viper envenomation. Myotoxins are an important part of the viper
      venomics. A Ser49 PLA2-like myotoxin from the venom of Vipera ammodytes
      meridionalis, the most venomous snake in Europe, was crystallized and its three
      dimensional structure determined. The toxin is devoid of phospholipolytic
      activity. The structure demonstrates a formation of dimers. In the dimers
      functionally important peptide segments, located on the protein surface, point in
      the same direction which can strengthen the pharmacological effect. This supports
      the hypothesis about the physiological importance of the toxin oligomerization
      for the myotoxicity and membrane damage. The crystallographic model revealed that
      the structural determinants of myotoxicity (a positively charged C-terminal
      region and a hydrophobic knuckle) are fully exposed on the protein surface and
      accessible for interactions with target membranes. Distortion of the catalytic
      site region explains the absence of enzymatic activity. The structure reveals
      anion-binding sites which can be considered as possible sites of interactions of
      the toxin with a negatively charged membrane surface. The high structural
      similarity of the Ser49 myotoxin and Asp49 PLA2 from the same venom suggests an
      evolutionary relationship: probably, the Ser49 myotoxin is a product of evolution
      of the catalytically active phospholipase A2. The first toxin lost the enzymatic
      activity which is not necessary for the myotoxicity but preserved the
      cytotoxicity and membrane damaging activity as important components of the venom
      toxicity.

PMID- 22362133
TI  - Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO
      RMs): comparison with NO donors.
AB  - Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet
      aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3,
      which releases CO rapidly (t (1/2) 1 min), and CORM-A1, which slowly releases CO
      (t(1/2) = 21 min). The anti-platelet effects of NO donors with various kinetics
      of NO release were studied for comparison. The effects of CO-RMs and NO donors
      were analyzed in washed human platelets (WP), platelets rich plasma (PRP), or
      whole blood (WB) using aggregometry technique. CORM-3 and CORM-A1 inhibited
      platelet aggregation in human PRP, WP, or WB, in a concentration-dependent
      manner. In all three preparations, CORM-A1 was more potent than CORM-3.
      Inhibition of platelets aggregation by CORM-A1 was not significantly affected by
      a guanylate cyclase inhibitor (ODQ) and a phosphodiesterase-5 inhibitor,
      sildenafil. In contrast, inhibition of platelet aggregation by NO donors was more
      potent with a fast NO releaser (DEA-NO, t (1/2) = 2 min) than slow NO releasers
      such as PAPA-NO (t (1/2) = 15 min) or other slow NO donors. Predictably, the anti
      platelet effect of DEA-NO and other NO donors was reversed by ODQ while
      potentiated by sildenafil. In contrast to NO donors which inhibit platelets
      proportionally to the kinetics of NO released via activation of soluble guanylate
      cyclase (sGC), the slow CO-releaser CORM-A1 is a superior anti-platelet agent as
      compared to CORM-3 which releases CO instantly. The anti-platelet action of CO
      RMs does not involve sGC activation. Importantly, CORM-A1 or its derivatives
      representing the class of slow CO releasers display promising pharmacological
      profile as anti-platelet agents.

PMID- 22362135
TI  - Dental visits, oral hygiene behaviour, and orthodontic treatment in Switzerland.
AB  - Since the first survey in 1992/93, the Swiss Health Survey (SHS) has been
      repeated every 5 years (1997, 2002 and 2007). In the present study, dental visits
      (dental care utilisation within the last 12 months), oral hygiene measures and
      the frequency of orthodontic treatments in the Swiss population in 2002 were
      examined and dental visits were compared with the years 1992/93, 1997 and 2007.
      Weighted data were analysed regarding different sociodemographic factors. From
      1992 to 2002, dental visits among the 15-74-year-old declined continuously
      (1992/93: 70%, 1997: 66%, 2002: 63%), whereas in 2007 a slight increase (66%) was
      documented. In the survey from 2002, a large proportion (74%) of the population
      stated to clean their teeth or prostheses several times a day, predominantly with
      a manual toothbrush, whereas 28% applied an electric toothbrush and almost half
      of the respondents also used dental floss or toothpicks. Fewer visits and less
      intensive oral hygiene measures were observed among the elderly, men, weak social
      strata, smokers, persons with more than 8 missing teeth and in the group with
      removable dentures. Almost a quarter of the population had orthodontic treatment
      with the highest proportion among the 15-24-year-old (56%).

PMID- 22362134
TI  - Modulation of histone deacetylase attenuates naloxone-precipitated opioid
      withdrawal syndrome.
AB  - The present study has been designed to investigate the effect of selective
      inhibitors of histone deacetylase and/or N-acetyl-Asp-Glu-Val-Asp-al (Ac-DEVD
      CHO), a selective interleukin-1beta converting enzyme inhibitor, on the
      development of naloxone-induced opioid withdrawal syndrome both in vitro and in
      vivo and the effect of histone deacetylase inhibition on histone H3 acetylation
      in brain. Sub-acute morphine administration followed by a single injection of
      naloxone (8 mg/kg, i.p.) was used to precipitate opioid withdrawal syndrome in
      mice. Behavioral observations were made immediately after naloxone treatment.
      Withdrawal syndrome was quantitatively assessed in terms of withdrawal severity
      score and frequency of jumping, rearing, fore paw licking and circling.
      Separately naloxone-induced contraction in morphine-dependent isolated rat ileum
      was employed as an in vitro model. An isobolographic study design was employed to
      assess potential synergistic activity between trichostatin A and Ac-DEVD-CHO.
      Brain histone acetylation status was examined by western blotting. Injection of
      naloxone precipitated a severe form of abstinence syndrome in morphine-dependent
      mice along with strong contracture in isolated rat ileum. Administration of
      tributyrin (1.5, 3 and 6 g/kg, p.o.), trichostatin A (0.3, 1.0 and 3.0 mg/kg,
      p.o.) and Ac-DEVD-CHO (0.3, 1.0 and 3.0 mg/kg, p.o.) markedly and dose
      dependently attenuated naloxone-induced morphine withdrawal syndrome in vivo as
      well as in vitro in rat ileum. Trichostatin A was also observed to exert a
      synergistic interaction with Ac-DEVD-CHO. Western blot analysis revealed that
      multiple administration with the effective dose of tributyrin or trichostatin A
      in the in vivo experiments induced hyperacetylation of histone H3 in the mouse
      brain. Thus, it is proposed that histone deacetylase activation linked mechanism
      might be involved in the development of opioid dependence and the precipitation
      of its withdrawal syndrome.

PMID- 22362136
TI  - Application of adaptive non-linear 2D and 3D postprocessing filters for reduced
      dose abdominal CT.
AB  - BACKGROUND: Abdominal computed tomography (CT) is a frequently performed imaging
      procedure, resulting in considerable radiation doses to the patient population.
      Postprocessing filters are one of several dose reduction measures that might help
      to reduce radiation doses without loss of image quality. PURPOSE: To assess and
      compare the effect of two- and three-dimensional (2D, 3D) non-linear adaptive
      filters on reduced dose abdominal CT images. MATERIAL AND METHODS: Two baseline
      abdominal CT image series with a volume computer tomography dose index (CTDI
      (vol)) of 12 mGy and 6 mGy were acquired for 12 patients. Reduced dose images
      were postprocessed with 2D and 3D filters. Six radiologists performed blinded
      randomized, side-by-side image quality assessments. Objective noise was measured.
      Data were analyzed using visual grading regression and mixed linear models.
      RESULTS: All image quality criteria were rated as superior for 3D filtered images
      compared to reduced dose baseline and 2D filtered images (P < 0.01). Standard
      dose images had better image quality than reduced dose 3D filtered images (P <
      0.01), but similar image noise. For patients with body mass index (BMI) < 30
      kg/m(2) however, 3D filtered images were rated significantly better than normal
      dose images for two image criteria (P < 0.05), while no significant difference
      was found for the remaining three image criteria (P > 0.05). There were no
      significant variations of objective noise between standard dose and 2D or 3D
      filtered images. CONCLUSION: The quality of 3D filtered reduced dose abdominal CT
      images is superior compared to reduced dose unfiltered and 2D filtered images.
      For patients with BMI < 30 kg/m(2), 3D filtered images are comparable to standard
      dose images.

PMID- 22362138
TI  - Solid-state thermolysis of ammonia borane and related materials for high-capacity
      hydrogen storage.
AB  - Ammonia borane (NH(3)BH(3), AB) is a unique molecular crystal containing an
      intriguingly high density of hydrogen. In the past several years, AB has received
      extensive attention as a promising hydrogen storage medium. Several strategies
      have been successfully developed for promoting H(2) release and for suppressing
      the evolution of volatile by-products from the solid-state thermolysis of AB.
      Several potentially cost-effective and energy-efficient routes for regenerating
      AB from the spent fuels have been experimentally demonstrated. These remarkable
      technological advances offer a promising prospect of using AB-based materials as
      viable H(2) carriers for on-board application. In this perspective, the recent
      progresses in promoting H(2) release from the solid-state thermolysis of AB and
      in developing regeneration technologies are briefly reviewed.

PMID- 22362137
TI  - The promoter region of the Zinnia elegans basic peroxidase isoenzyme gene
      contains cis-elements responsive to nitric oxide and hydrogen peroxide.
AB  - NO and H2O2 are important biological messengers in plants. They are formed during
      xylem differentiation in Zinnia elegans and apparently play important roles
      during the xylogenesis. To ascertain the responsiveness of the Z. elegans
      peroxidase (ZePrx) to these endogenous signals, the effects of NO and H2O2 on
      ZePrx were studied. The results showed that ZePrx is up-regulated by NO and H2O2,
      as confirmed by RT-qPCR, and that its promoter contains multiple copies of all
      the putative cis-elements (ACGT box, OCS box, OPAQ box, L1BX, MYCL box and W box)
      known to confer regulation by NO and H2O2. Like other OCS elements, the OCS
      element of ZePrx contains the sequence TACG that is recognized by OBF5, a highly
      conserved bZIP transcription factor, and the 10 bp sequence, ACAaTTTTGG, which is
      recognized by OBP1, a Dof domain protein that binds down-stream the OCS element.
      Furthermore, the ZePrx OCS element is flanked by two CCAAT-like boxes, and
      encloses one auxin-responsive ARFAT element and two GA3-responsive Pyr boxes.
      Results also showed that ZePrx may be described as the first protein to be up
      regulated by NO and H2O2, whose mRNA contains several short-longevity conferring
      elements, such as a downstream (DST) sequence analogous to the DSTs contained in
      the highly unstable SAUR transcripts. The presence of these regulatory elements
      strongly suggests that ZePrx is finely regulated, as one may expect from an
      enzyme that catalyzes the last irreversible step of the formation of lignins, the
      major irreversible sink for the photosynthetically fixed CO2.

PMID- 22362139
TI  - Effect of polysorbate 80 quality on photostability of a monoclonal antibody.
AB  - Polysorbate 80 is one of the key components of protein formulations. It primarily
      inhibits interfacial damage of the protein molecule due to mechanical stress
      during shipping and handling. However, polysorbate 80 also affects the
      formulation photostability. Exposure to light of polysorbate 80 aqueous solution
      results in peroxide generation, which in turn may result in oxidation of the
      susceptible amino acid residues in the protein molecule. The purpose of this
      study was to determine if the photostability of our proprietary IgG(1) monoclonal
      antibody formulation containing polysorbate 80 is affected by the quality
      (grade/vendor) of polysorbate 80. Following four types of polysorbate 80 were
      tested: (1) Polysorbate 80 Super-Refined, Mallinckrodt Baker, (2) Polysorbate 80
      NF, Mallinckrodt Baker, (3) Polysorbate 80 NF, EMD Chemicals, and (4) Ultra-pure
      Polysorbate 80 (HX), NOF Corporation. The samples were exposed to light as per
      ICH guidelines Q1B. The results of the study show that photostability of the
      antibody formulation is indeed affected by the quality of polysorbate 80. This
      study underscores the importance of carefully choosing the quality of polysorbate
      80 to ensure the robustness of formulation.

PMID- 22362140
TI  - Optimization of an aqueous tablet-coating process containing carboxymethylated
      Cassia fistula gum.
AB  - The present investigation was aimed at developing and optimizing a simple aqueous
      tablet-coating formulation and its process. 5-Fluorouracil (5-FU) was used to
      ascertain the relative lipophilic/hydrophilic behavior of the coating system.
      Optimization was performed by evaluating the adhesive force strength and cohesive
      force strength of the tablet coat using a texture analyzer. The in vitro release
      of 5-FU was found to decrease with an increase in (tablet surface-coat) adhesive
      force strength. The (tablet-tablet) cohesive force strength was reduced by the
      addition of magnesium silicate to the coating solution. The addition of magnesium
      silicate (0.2% w/v) to the carboxymethyl Cassia fistula gum-chitosan (CCG-CH)
      coating surface significantly inhibited the release of 5-FU possibly due to an
      increase in the hydrophobic character of the coated tablet surface. This was
      possible by coating cohesive force strength reduction coating compositions (CCG
      CH (70:30) and 0.3% magnesium silicate). Further, the FTIR-ATR and DSC analyses
      suggested the pivotal role of magnesium silicate in modifying the release of 5-FU
      from CCG-CH-coated tablets due to hydrogen bonding of its Si-O-Si or Mg-O groups
      with -OH moieties of CCG-CH.

PMID- 22362141
TI  - Antioxidant activities of Perilla frutescens against low-density lipoprotein
      oxidation in vitro and in human subjects.
AB  - Perilla (Perilla frutescens (L.) Britt.) is a popular food as well as a
      traditional medicine in Japan, China, and other Asian countries. The aim of this
      study was to investigate the inhibitory effects of perilla on low-density
      lipoprotein (LDL) oxidation in vitro and in human subjects. We compared the
      antioxidant activities of red perilla and green perilla. Both green and red
      perilla had high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and
      were abundant in polyphenol compounds. In addition, the radical scavenging
      activity and polyphenol content of red perilla were higher than those of green
      perilla. Perilla dramatically inhibited azo-radical-induced LDL oxidation and
      endothelial-cell-mediated LDL oxidation in vitro. Moreover, red perilla
      significantly increased mRNA and protein expression levels of antioxidant enzymes
      in endothelial cells. We further examined the antioxidant effects against LDL in
      human subjects after the consumption of perilla extracts. After oral intake of
      red perilla, the subjects' LDL oxidation lag times were significantly longer than
      those before the intake. Furthermore, lipid peroxide formation and the
      electrophoretic mobility of LDL decreased markedly. These results suggested that
      perilla, especially the red variety, had high antioxidant activity and prevented
      the oxidation of LDL, which is a process strongly related to the development of
      atherosclerosis.

PMID- 22362142
TI  - Color and chemical properties of oil used for deep frying on a large scale.
AB  - Acid value (AV), polar compound content (PC), carbonyl value (CV) and Gardner
      color of oil used for deep-frying in kitchens at a supermarket, lunch chain
      store, restaurant, eating house, and hospital were analyzed. All AVs obtained but
      one (3.38) were within the limit set by the Food Sanitation Act of Japan (AV <=
      3, peroxide value <= 30). However, some oil samples had a PC over 25%, which is
      beyond the limit legislated by some European countries. When the relation between
      the Gardner color and the AV, PC, or CV of the oil was investigated, well
      correlated logarithmic regression curves were obtained from the oil of all
      kitchens except the hospital kitchen. However, the use of lard-containing canola
      oil without oil replenishment in the eating house increased color values rapidly.
      All of the values obtained from pure vegetable oil used almost daily were plotted
      on a graph. It was found that kitchen-by-kitchen differences in fryer, vegetable
      oil, frying temperature, heating time, and amounts and kinds of foods fried did
      not influence the relation between Gardner color value versus AV, PC or CV. In
      conclusion, frying vegetable oil used in large-scale kitchens without official
      inspection can be better controlled with Gardner color determination by the
      operators and administrators. This would improve the quality of the oil ingested
      by facility patrons.

PMID- 22362143
TI  - Electronic modification effects induced by Fe in Pt-Ru-Fe ternary catalyst on the
      electrooxidation of CO/H2 and methanol.
AB  - Electro-oxidation of CO/H2 and methanol was performed over a carbon supported Pt
      Ru-Fe ternary alloy catalyst prepared via the conventional NaBH4 reduction
      method. Physicochemical and electrochemical measurements were used to elucidate
      the respective roles of Ru and Fe in the ternary catalyst, revealing synergistic
      effects in the Pt-Ru-Fe catalyst on the electro-oxidation of CO/H2 and methanol.
      The methanol oxidation activity of Pt3Ru2Fe/C was ca. 2.5 times higher than that
      of PtRu/C at 0.45 V vs. RHE as a result of enhanced CO tolerance. The enhanced CO
      tolerance of the Pt-Ru-Fe ternary alloy catalysts was derived from the reaction
      between the high mobility, weakly adsorbed CO on the Pt site that was
      electronically modified by alloying with Fe and adsorbed water species on the Ru
      site. This combination of features produced an improvement in the electro
      oxidation of CO/H2 and methanol at lower potential. On the basis of the data, it
      was proposed that the addition of a water activator such as Ru is indispensible
      in the design of multicomponent alloy catalysts for methanol oxidation, and the
      additional effect derived from an electronic modifier is an important factor for
      improving the CO and methanol oxidation activity of the catalyst containing the
      water activator.

PMID- 22362144
TI  - Phase behavior of phytosterol ethoxylates in an imidazolium-type room-temperature
      ionic liquid.
AB  - The temperature-concentration phase behavior of nonionic surfactants in an
      aprotic imidazolium-type room-temperature ionic liquid (RT-IL) was evaluated on
      the basis of a combination of visual appearance, polarized optical microscopy,
      and small angle X-ray scattering data. Phytosterol ethoxylates (BPS-n, where n
      denotes oxyethylene chain lengths of 5, 10, 20, and 30) were used as surfactants
      in the RT-IL, 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6). The two
      component mixtures yielded various phases such as discontinuous cubic, hexagonal,
      and lamellar phases. An increased tendency toward formation of lesser-curved
      molecular assemblies was observed at higher BPS-n concentrations, at lower
      temperatures, and for shorter oxyethylene chain surfactants. These trends are
      similar to those observed in aqueous BPS-n systems; however, notable differences
      in the phase states of the aqueous system versus the BmimPF6 system were evident.
      Comparison with the water system showed that the BmimPF6 system yielded fewer
      phases and generally required higher BPS-n concentrations to induce phase
      transitions. Evaluation of the effects of addition of a third component (e.g., 1
      dodecanol and dodecane) to the binary system on the phase behavior showed that at
      a given composition ratio of BPS-20 to BmimPF6, the addition of 1-dodecanol
      generally results in the phase transition to lesser-curved assemblies whereas
      dodecane generated no significant effects. The observed phase change is
      satisfactorily rationalized by localized solubilization of the third component
      into the binary surfactant assemblies.

PMID- 22362145
TI  - Identification of a novel mutation in FAD2B from a peanut EMS mutant with
      elevated oleate content.
AB  - A Virginia type peanut mutant with more than 60% oleate content (E2-4-83-12) was
      selected from an EMS mutagenized population of LF2 (an export type peanut
      cultivar with 44.2% oleate) by near infrared reflectance spectroscopy. Cloning
      and sequencing of FAD2B from LF2 and E2-4-83-12 identified a novel mutation
      (C313T in the coding region) causing an H105Y substitution in the first histidine
      box of the FAD2B protein. GC-MS analysis of fatty acids in yeast cells harboring
      pYES2 with the mutated FAD2B detected no linoleate, confirming that FAD2B from E2
      4-83-12 was dysfunctional. Loss-of-function FAD2A and FAD2B together contributed
      to elevated oleate phenotype of the peanut EMS mutant.

PMID- 22362146
TI  - Adsorption capacity of Cu(II) and Pb(II) onto carbon fiber produced from wool.
AB  - The potential utility of the widely available waste product, wool textiles, in
      the adsorption of heavy metals from industrial and other wastewater systems was
      investigated by proxy experimentation. Carbon fiber was prepared from dyed wool
      (DW) by calcination at different temperatures (400, 600, 800, and 1000  degrees
      C, referred to as DW400, DW600, DW800, and DW1000, respectively). The samples
      were analyzed in terms of scanning electron microscope images, percentage yield,
      specific surface area, pore volume, and the pH of an aqueous suspension of virgin
      dyed wool (V-DW) or the calcined DW. The adsorption of Cu(II) and Pb(II) from
      aqueous solutions was studied using the batch method, and the effect of contact
      time and co-existence of metal ions was investigated. Cu(II) and Pb(II)
      adsorption increased with increasing DW calcination temperature in the order V-DW
      < DW400 < DW600 < DW800 < DW1000. The maximum equilibrium adsorption of Cu (II)
      and Pb(II) achieved with DW1000 (79% and 57%, respectively) was reached within 6
      h. Fitting of the adsorption isotherm data for Cu(II) and Pb(II) adsorption onto
      DW1000 to the Freundlich equation was consistent with monomolecular adsorption
      onto a heterogeneous surface. The rate-limiting step was determined to be
      chemical sorption by fitting the adsorption kinetics data to pseudo first-order
      and pseudo second-order models, given that the pseudo second-order model best fit
      our data. The study demonstrated that DW1000 was useful for purification of
      wastewater containing Cu(II) and Pb(II).

PMID- 22362147
TI  - Rapid reductive dechlorination of trichloroethene in contaminated ground water
      using biostimulation agent, BD-1, formulated from canola oil.
AB  - A case study of the bioremediation of groundwater contaminated with
      trichloroethene (TCE) was conducted using the biostimulation agent, BD-1. TCE
      levels were monitored by gas chromatography-mass spectroscopy. Total organic
      carbon (TOC) and volatile fatty acids (VFAs) were analyzed to investigate the
      environmental fate of BD-1. The effects of BD-1 on microbial activity were
      investigated using 16S rRNA gene-based quantitative polymerase chain reaction
      (qPCR) analysis. The biodegradation of BD-1 was accompanied by a reduction in
      TCE, and the initially high TOC levels decreased rapidly as BD-1 was transformed
      into VFAs. qPCR analysis showed that the genus Dehalobacter became progressively
      dominant through the experiment. These results suggested that BD-1 might
      dechlorinate TCE by activating dechlorinating bacteria.

PMID- 22362148
TI  - Cell selective conditional null mutations of serine racemase demonstrate a
      predominate localization in cortical glutamatergic neurons.
AB  - D-serine, which is synthesized by the enzyme serine racemase (SR), is a co
      agonist at the N-methyl-D-aspartate receptor (NMDAR). Crucial to an understanding
      of the signaling functions of D-serine is defining the sites responsible for its
      synthesis and release. In order to quantify the contributions of astrocytes and
      neurons to SR and D-serine localization, we used recombinant DNA techniques to
      effect cell type selective suppression of SR expression in astrocytes (aSRCKO)
      and in forebrain glutamatergic neurons (nSRCKO). The majority of SR is expressed
      in neurons: SR expression was reduced by ~65% in nSRCKO cerebral cortex and
      hippocampus, but only ~15% in aSRCKO as quantified by western blots. In contrast,
      nSRCKO is associated with only modest decreases in D-serine levels as quantified
      by HPLC, whereas D-serine levels were unaffected in aSRCKO mice. Liver expression
      of SR was increased by 35% in the nSRCKO, suggesting a role for peripheral SR in
      the maintenance of brain D-serine. Electrophysiologic studies of long-term
      potentiation (LTP) at the Schaffer collateral-CA1 pyramidal neuron synapse
      revealed no alterations in the aSRCKO mice versus wild-type. LTP induced by a
      single tetanic stimulus was reduced by nearly 70% in the nSRCKO mice.
      Furthermore, the mini-excitatory post-synaptic currents mediated by NMDA
      receptors but not by AMPA receptors were significantly reduced in nSRCKO mice.
      Our findings indicate that in forebrain, where D-serine appears to be the
      endogenous co-agonist at NMDA receptors, SR is predominantly expressed in
      glutamatergic neurons, and co-release of glutamate and D-serine is required for
      optimal activation of post-synaptic NMDA receptors.

PMID- 22362151
TI  - Surface-Enhanced Raman Scattering (SERS) on transition metal and semiconductor
      nanostructures.
AB  - Surface-Enhanced Raman Scattering (SERS) spectroscopy has experienced a rapid
      growth over the past 30 years, and has become a valuable tool in various research
      areas. In conjunction with recent explosive development of nanoscience and
      nanotechnology, the SERS-active substrates have also expanded from traditional
      Group 11 metals (Au, Ag, Cu) to non-Group 11 nanostructures. This paper gives an
      overview of historical advances in the use of non-Group 11 nanostructures as
      substrates for SERS. Several possible mechanisms and important factors for SERS
      from non-Group 11 nanostructures are discussed in detail. The SERS from non-Group
      11 nanostructures provides many significant applications in surface, interface
      analysis and biochemical detection. It is reasonable to believe that the
      advancement in the non-Group 11 nanostructures-based SERS-active substrates will
      lead to a more promising future for the SERS technology in surface science,
      spectroscopy and biomedicine.

PMID- 22362149
TI  - Role of the cellular prion protein in the neuron adaptation strategy to copper
      deficiency.
AB  - Copper transporter 1 (CTR1), cellular prion protein (PrP(C)), natural resistance
      associated macrophage protein 2 (NRAMP2) and ATP7A proteins control the cell
      absorption and efflux of copper (Cu) ions in nervous tissues upon physiological
      conditions. Little is known about their regulation under reduced Cu availability,
      a condition underlying the onset of diffused neurodegenerative disorders. In this
      study, rat neuron-like cells were exposed to Cu starvation for 48 h. The
      activation of Caspase-3 enzymes and the impairment of Cu,Zn superoxide dismutase
      (Cu,Zn SOD) activity depicted the initiation of a pro-apoptotic program,
      preliminary to the appearance of the morphological signs of apoptosis. The
      transcriptional response related to Cu transport proteins has been investigated.
      Notably, PrP(C) transcript and protein levels were consistently elevated upon Cu
      deficiency. The CTR1 protein amount was stable, despite a two-fold increase in
      the transcript amount, meaning the activation of post-translational regulatory
      mechanisms. NRAMP2 and ATP7A expressions were unvaried. The up-regulated PrP(C)
      has been demonstrated to enhance the cell Cu uptake ability by about 50% with
      respect to the basal transport, and so sustain the Cu delivery to the Cu,Zn SOD
      cuproenzymes. Conclusively, the study suggests a pivotal role for PrP(C) in the
      cell adaptation to Cu limitation through a direct activity of ion uptake. In this
      view, the PrP(C) accumulation observed in several cancer cell lines could be
      interpreted as a molecular marker of cell Cu deficiency and a potential target of
      therapeutic interventions against disorders caused by metal imbalances.

PMID- 22362150
TI  - An association study on the polymorphisms of dopaminergic genes with working
      memory in a healthy Chinese Han population.
AB  - Working memory (WM) is a highly heritable cognitive trait that is involved in
      many higher-level cognitive functions. In the past few years, much evidence has
      indicated that the reduction of dopamine activity in human brain can impair the
      WM system of the neuropsychiatric disorders. In this study, we hypothesized that
      some genes in the dopamine system were involved in the individual difference of
      the cognitive ability in healthy population. To confirm this hypothesis, a
      population-based study was performed to examine the effects of COMT, DAT (1), DRD
      (1), DRD (2), DRD (3), and DRD (4) on WM spans. Our results indicated there were
      significant associations of TaqIA and TaqIB in DRD (2) with digital WM span,
      respectively (chi(2) = 9.460, p = 0.009; chi(2) = 6.845, p = 0.033). On the other
      hand, we found a significant interaction between Ser9Gly in DRD (3) and TaqIA of
      DRD (2) on digital WM span (F = 3.207, p = 0.013). COMT, DAT (1) , DRD (1), and
      DRD (4), however, had no significant effects on digital and spatial WM spans
      (chi(2)<3.84, p > 0.05). These preliminary results further indicated that certain
      functional variants in dopamine system, such as TaqIA and TaqIB of DRD (2), were
      possibly involved in difference of WM in a healthy population.

PMID- 22362152
TI  - Preservation HIV-1-specific IFNgamma+ CD4+ T-cell responses in breakthrough
      infections after exposure to tenofovir gel in the CAPRISA 004 microbicide trial.
AB  - The Centre for the AIDS Program of Research in South Africa 004 trial
      demonstrated reduction of sexual HIV-1 acquisition in women using a vaginal
      microbicide containing tenofovir. A better understanding of the consequences of
      antiretroviral-containing microbicides for immune responses in individuals with
      intercurrent HIV-1 infection is needed for future trials combining the use of
      microbicides with HIV-1 vaccines. Investigation of immune responses in women who
      acquired HIV-1 although using tenofovir gel showed significantly higher (P =
      0.01) Gag-specific IFNgamma+ CD4+ T-cell responses. The use of tenofovir
      containing gel around the time of infection can modulate HIV-1 immunity, and
      these immunological changes need to be considered in future trials combining
      vaccines and microbicides.

PMID- 22362153
TI  - Differences in virological response to peginterferon-alpha plus ribavirin in HIV
      positive patients coinfected with HCV subtypes 1a or 1b.
AB  - BACKGROUND: Both viral and host factors influence response to peginterferon-alpha
      plus ribavirin (pegIFNalpha/RBV) in patients with chronic hepatitis C. The impact
      of these variables is more pronounced in HIV/Hepatitis C virus (HCV)-coinfected
      individuals, in whom treatment response rates are lower. METHODS: Virological
      responses at multiple time points were assessed in all HIV/HCV-coinfected
      patients that completed a first course of pegIFNalpha/RBV. Viral responses were
      stratified by HCV geno/subtypes and IL28B rs12979860 variants. RESULTS: A total
      of 331 HIV/HCV-coinfected patients were analyzed. HCV geno/subtype distribution
      was as follows: HCV-1a in 97, HCV-1b in 62, HCV-3 in 122, and HCV-4 in 50. Age,
      gender, CD4 counts, plasma HIV RNA and liver fibrosis stage did not differ
      significantly across HCV geno/subtypes. In contrast, mean serum HCV RNA was
      greater in HCV-1a compared with the rest (P < 0.0001). The proportion of IL28B CC
      variants was higher in HCV-3 compared with the rest (P = 0.001). Virological
      responses were better in HCV-1b than HCV-1a at any given time point during
      therapy. IL28B variants significantly influenced virological responses across all
      HCV-1 subtypes, with the strongest effect seen in HCV-1a. In a multivariate
      linear regression analysis, both HCV-1b and IL28B CC variants were significantly
      associated with greater HCV RNA drops at weeks 4 (R = 0.52, p < 0.0001) and 12 (R
      = 0.49, P < 0.0001) of therapy. CONCLUSIONS: The response to pegIFNalpha/RBV
      therapy is lower in HCV-1a than HCV-1b in HIV/HCV-coinfected patients. The
      strongest influence of IL28B variants is seen in HCV-1a. This information may be
      relevant when using most directly acting antivirals in coinfected patients along
      with pegIFNalpha/RBV, given that selection of drug resistance occurs more
      frequently in HCV-1a than HCV-1b.

PMID- 22362155
TI  - Mitochondrial evolution in HIV-infected children receiving first- or second
      generation nucleoside analogues.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) and HIV-related
      mitochondrial toxicity lead to several adverse effects and have become a major
      issue, especially in children. The main goal in the treatment of HIV-infected
      children is to maximize cost-effectiveness while minimizing toxicity. We aimed to
      study the evolution of mitochondrial parameters over time in children receiving
      different types antiretroviral regimens. METHODS: We followed-up 28 HIV-infected
      children receiving HAART including either first-generation nucleoside reverse
      transcriptase inhibitors (1gNRTIs; didanosine, zidovudine, or stavudine; n = 15)
      or second-generation NRTIs (2gNRTIs; the remaining drugs; n = 13) for a period of
      2 years for their immunovirological and mitochondrial status, and compared these
      subjects with a group of untreated HIV-infected patients (n = 10) and uninfected
      controls (n = 27). We measured T-lymphocyte CD4+ content (flow cytometry), viral
      load (real-time polymerase chain reaction), and lactate levels
      (spectrophotometry); we assessed mtDNA content (real-time polymerase chain
      reaction), mitochondrial protein levels (Western blot), oxidative stress,
      mitochondrial mass, and electron transport chain function (spectrophotometry) in
      peripheral blood mononuclear cells. RESULTS: At the second time point, lactate
      levels were significantly higher in children on 1gNRTIs compared with those
      receiving 2gNRTIs (1.28 +/- 0.08 vs. 1.00 +/- 0.07 mmol/L, respectively; P =
      0.022). MtDNA content was similar among all HIV-infected groups and significantly
      lower than in healthy controls at baseline. Oxidative stress tended to increase
      over time in all the groups, with no differences among them. However, a
      significant decrease in cytochrome c oxidase activity was found over time in HIV
      infected patients; this decline was greater in the 1gNRTIs group. CONCLUSIONS:
      HIV infection and the use of 1gNRTIs caused greater mitochondrial damage than
      2gNRTIs over time. The higher lactate levels and the significant decrease
      observed in cytochrome c oxidase activity argue against the use of 1gNRTIs in HIV
      infected children when an alternative is available, in accordance with
      international recommendations.

PMID- 22362154
TI  - Feasibility of using flash-heated breastmilk as an infant feeding option for HIV
      exposed, uninfected infants after 6 months of age in urban Tanzania.
AB  - OBJECTIVE: Heat-treating expressed breastmilk is recommended as an interim
      feeding strategy for HIV-exposed infants in resource-poor countries, but data on
      its feasibility are minimal. Flash-heating (FH) is a simple in-home technique for
      heating breastmilk that inactivates HIV although preserving its nutritional and
      anti-infective properties. Our primary objective was to determine, among HIV
      infected mothers, the feasibility and protocol adherence of FH expressed
      breastmilk after 6 months of exclusive breastfeeding. DESIGN: Prospective
      longitudinal. PARTICIPANTS: One hundred one HIV-infected breastfeeding mothers.
      SETTING: Dar es Salaam, Tanzania. INTERVENTION: Peer counselors provided in-home
      counseling and support on infant feeding from 2 to 9 months postpartum. Mothers
      were encouraged to exclusively breastfeed for 6 months followed by FH expressed
      breastmilk if her infant was HIV negative. Clinic-based staff measured infant
      growth and morbidity monthly, and mothers kept daily logs of infant morbidity. FH
      behavior was tracked until 9 months postpartum using daily logs, in-home
      observations, and clinic-based and home-based surveys. Bacterial cultures of
      unheated and heated milk samples were performed. RESULTS: Thirty-seven of 72
      eligible mothers (51.4%) chose to flash-heat. Median (range) frequency of milk
      expression was 3 (1-6) times daily and duration of method use on-study was 9.7
      (0.1-15.6) weeks. Mean (SD) daily milk volume was 322 (201) mL (range 25-1120).
      No heated and 32 (30.5%) unheated samples contained bacterial pathogens.
      CONCLUSIONS: FH is a simple technology that many HIV-positive women can
      successfully use after exclusive breastfeeding to continue to provide the
      benefits of breastmilk while avoiding maternal-to-child transmission associated
      with nonexclusive breastfeeding. Based on these feasibility data, a clinical
      trial of the effects of FH breastmilk on infant health outcomes is warranted.

PMID- 22362156
TI  - A cost analysis of an Internet-based medication adherence intervention for people
      living with HIV.
AB  - The purpose of the study was to document development costs and estimate
      implementation costs of an Internet-based medication adherence intervention for
      people living with HIV in the United States. Participants (n = 61) were enrolled
      in the 8-week study in 2011 and entered the intervention website remotely in the
      setting of their choice. Development costs were obtained from a feasibility and
      acceptability study of an Internet-based medication adherence intervention.
      Implementation costs were estimated based on an 8-week trial period during the
      feasibility and acceptability study. Results indicated that although developing
      an Internet-based medication adherence intervention is expensive, the monthly
      cost of implementing and delivering the intervention is low. If the efficacy of
      similar interventions can be established, these results suggest that Internet
      could be an effective method for delivering medication adherence interventions to
      persons residing in areas with limited access to in-person adherence services.

PMID- 22362157
TI  - Extinction of conditioned opiate withdrawal in rats in a two-chambered place
      conditioning apparatus.
AB  - Conditioned opiate withdrawal contributes to relapse in addicts and can be
      studied in rats by using the opiate withdrawal-induced conditioned place aversion
      (OW-CPA) paradigm. Attenuation of conditioned withdrawal through extinction may
      be beneficial in the treatment of addiction. Here we describe a protocol for
      studying OW-CPA extinction using a two-chambered place conditioning apparatus.
      Rats are made dependent on morphine through subcutaneous implantation of morphine
      pellets and then are trained to acquire OW-CPA through pairings of one chamber
      with naloxone-precipitated withdrawal and the other chamber with saline.
      Extinction training consists of re-exposures to both chambers in the absence of
      precipitated withdrawal. Rats tested after the completion of training show a
      decline in avoidance of the formerly naloxone-paired chamber with increasing
      numbers of extinction training sessions. The protocol takes a minimum of 7 d; the
      exact duration varies with the amount of extinction training, which is determined
      by the goals of the experiment.

PMID- 22362158
TI  - Assessing fear and anxiety in humans using the threat of predictable and
      unpredictable aversive events (the NPU-threat test).
AB  - The threat of predictable and unpredictable aversive events was developed to
      assess short-duration (fear) and long-duration (anxiety) aversive states in
      humans. A typical experiment consists of three conditions: a safe condition
      (neutral (N)), during which participants are safe from aversive stimuli, and two
      threat conditions-one in which aversive events are administered predictably (P)
      (i.e., signaled by a threat cue), and one in which aversive stimuli are
      administered unpredictably (U). During the so-called NPU-threat test, ongoing
      change in aversive states is measured with the startle reflex. The NPU-threat
      test has been validated in pharmacological and clinical studies and can be
      implemented in children and adults. Similar procedures have been applied in
      animal models, making the NPU-threat test an ideal tool for translational
      research. The procedure is relatively short (35 min), simple to implement and
      generates consistent results with large effect sizes.

PMID- 22362159
TI  - In situ localization of small RNAs in plants by using LNA probes.
AB  - Small RNAs have crucial roles in numerous aspects of plant biology. Despite our
      current understanding of their biogenesis and mechanisms of action, the
      biological function of small RNAs, particularly miRNAs, remains largely unknown.
      To decipher small RNA function, knowledge about their spatiotemporal patterns of
      expression is essential. Here we report an in situ hybridization method for the
      precise localization of small RNAs in plants by using locked nucleic acid (LNA)
      oligonucleotide probes. This method has been adapted from protocols used to
      detect messenger RNAs in formaldehyde-fixed and paraffin-embedded tissue
      sections, but it includes essential optimizations in key prehybridization,
      hybridization and posthybridization steps. Most importantly, optimization of
      probe concentration and hybridization temperature is required for each unique LNA
      probe. We present the detailed protocol starting from sectioned tissues, and we
      include troubleshooting tips and recommended controls. This method has been used
      successfully in several plant species and can be completed within 2-6 d.

PMID- 22362160
TI  - 5' end-centered expression profiling using cap-analysis gene expression and next
      generation sequencing.
AB  - Cap-analysis gene expression (CAGE) provides accurate high-throughput measurement
      of RNA expression. CAGE allows mapping of all the initiation sites of both capped
      coding and noncoding RNAs. In addition, transcriptional start sites within
      promoters are characterized at single-nucleotide resolution. The latter allows
      the regulatory inputs driving gene expression to be studied, which in turn
      enables the construction of transcriptional networks. Here we provide an
      optimized protocol for the construction of CAGE libraries on the basis of the
      preparation of 27-nt-long tags corresponding to initial bases at the 5' ends of
      capped RNAs. We have optimized the methods using simple steps based on
      filtration, which altogether takes 4 d to complete. The CAGE tags can be readily
      sequenced with Illumina sequencers, and upon modification they are also amenable
      to sequencing using other platforms.

PMID- 22362161
TI  - Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor,
      in patients with advanced solid tumors and lymphomas.
AB  - PURPOSE: Chidamide (CS055/HBI-8000) is a new benzamide class of histone
      deacetylase inhibitor with marked anti-tumor activity. This study reports the
      phase I results. METHODS: Patients with advanced solid tumors or lymphomas
      received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice
      (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks.
      Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and
      preliminary efficacy were evaluated. RESULTS: A total of 31 patients were
      enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade
      3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively.
      PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a
      dose-related increase in C(max) and AUC. Significant induction of histone H3
      acetylation in peripheral white blood cells was observed after a single dose of
      chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular
      adenoid cystic carcinoma achieved a partial response. CONCLUSIONS: Chidamide was
      generally well tolerated in patients with advanced solid tumors or lymphomas in
      the tested regimens. Favorable PK and PD profiles, as well as encouraging
      preliminary anti-tumor activity, were demonstrated.

PMID- 22362162
TI  - Pineal parenchymal tumor of intermediate differentiation with marked elevation of
      MIB-1 labeling index.
AB  - We report a case of pineal parenchymal tumor (PPT) in an 11-year-old girl. Brain
      magnetic resonance imaging (MRI) revealed a large tumor (48 mm) located in the
      pineal region with heterogeneous enhancement after gadolinium administration. The
      patient underwent tumor removal with craniotomy; only partial tumor resection
      could be performed because of massive intratumoral bleeding. Histopathological
      examination of the tumor showed lobular proliferation of round cells with
      moderate atypia. Cellularity varied by area, and focal Homer Wright rosettes were
      identified. Examination of tumor cells revealed a few mitoses (two mitotic
      figures per 10 high-powered fields), and immunohistochemical staining revealed
      positivity for synaptophysin, slight positivity for neurofilament protein (NFP)
      with antibody clone 2F11, and strong positivity for NFP with clone NF-M+H. The
      pathological diagnosis was pineal parenchymal tumor of intermediate
      differentiation grade II according to World Health Organization criteria despite
      a high (22%) MIB-1 labeling index (LI). The patient had a favorable clinical
      course after an intensified chemotherapy regimen designed for pineoblastoma and
      radiotherapy administered to the entire neuraxis, followed by stereotactic
      radiotherapy. In conclusion, MIB-1 LI could be a useful tool for deciding
      therapeutic strategies for PPT treatment when there is a discrepancy between
      clinical findings and pathological grading.

PMID- 22362163
TI  - Effect of mothering on the spatial exploratory behavior of quail chicks.
AB  - Previous maternal deprivation experiments demonstrated that absence of maternal
      care impacts the behavioral development of young animals. Here we assessed the
      influence of the presence of a mothering hen on the spatial exploration of
      Japanese quail chicks, after the mothering period. Brooded and nonbrooded chicks
      were placed in a novel environment containing feeding troughs. The distribution
      of chicks and their inter-individual distances were measured during repeated
      tests. Brooded chicks exhibited a higher ability to disperse, thereby
      progressively exploiting larger surfaces and gaining access to food more easily.
      The fact that exploration by nonbrooded chicks was delayed suggests a deficit in
      their exploratory motivation and/or spatial skills. We hypothesize that brooded
      chicks experienced the constraint to follow the mothering hen, and to adapt to
      frequent reconfigurations of their environment. The lack of this variability in
      the environment of nonbrooded chicks could have reduced adaptability of their
      spatial behavior.

PMID- 22362164
TI  - Growth of long and aligned multi-walled carbon nanotubes on carbon and metal
      substrates.
AB  - Well aligned, long and dense multi-walled carbon nanotubes (CNT) can be grown on
      both carbon fibres and any metal substrates compatible with the CNT synthesis
      temperature. The injection-CVD process developed involves two stages, including
      fibre pretreatment by depositing a SiO(2)-based sub-layer from an organometallic
      precursor followed by CNT growth from toluene/ferrocene precursor mixture. Carbon
      substrates, as well as metals, can easily be treated with this process, which
      takes place in the same reactor and does not need any handling in between the two
      stages. The aligned CNT carpets obtained are similar to the ones grown on
      reference quartz substrates. The CNT growth rate is fairly high (ca. 30 MUm min(
      1)) and it is possible to control CNT length by varying the CNT synthesis
      duration. The thickness of the SiO(2)-based sub-layer can be varied and is shown
      to have an influence on the CNT growth. This layer is assumed to play a diffusion
      barrier layer role between the substrate and the iron based catalyst
      nanoparticles producing CNT. The CNT anchorage to the carbon fibres has been
      checked and good overall adhesion proved, which is in favour of a good transfer
      of electrical charge and heat between the nanotubes and fibre.

PMID- 22362165
TI  - Parallel tracking of cAMP and PKA signaling dynamics in living cells with FRET
      based fluorescent biosensors.
AB  - Proper regulation of cellular functions relies upon a network of intricately
      interwoven signaling cascades in which multiple components must be tightly
      coordinated both spatially and temporally. To better understand how this network
      operates within the cellular environment, it is important to define the
      parameters of various signaling activities and to reveal the characteristic
      activity structure of the signaling cascades. This task calls for molecular tools
      capable of parallelly tracking multiple activities in cellular time and space
      with high sensitivity and specificity. Here, we present new biosensors developed
      based on two conveniently co-imageable FRET pairs consisting of CFP-RFP and YFP
      RFP, specifically Cerulean-mCherry and mVenus-mCherry, for parallel monitoring of
      PKA activity and cAMP dynamics in living cells. These biosensors provide
      orthogonal readouts in co-imaging experiments and display a comparable dynamic
      range to their cyan-yellow counterparts. Characterization of signaling responses
      induced by a panel of pathway activators using this co-imaging approach reveals
      distinct activity and kinetic patterns of cAMP and PKA dynamics arising from
      differential signal activation and processing. This technique is therefore useful
      for parallel monitoring of multiple signaling dynamics in single living cells and
      represents a promising approach towards a more precise characterization of the
      activity structure of the dynamic cellular signaling network.

PMID- 22362166
TI  - Hepatitis B infection in the Asian and Latino communities of Alameda County,
      California.
AB  - The purpose of this study is to estimate the prevalence of the hepatitis B virus
      (HBV) infection and to examine factors related to HBV screening and vaccination
      among various Asian and Latino populations in Alameda County, CA. A cross
      sectional study was conducted on Asian and Latino residents who registered with
      an HBV screening program from June 2009-February 2011. All participants completed
      a sociodemographic survey and were offered free HBV blood testing for the
      hepatitis B surface antigen (HBsAg) and antibody (HBsAb). The 3-shot vaccination
      series was provided for free to unprotected participants. Among the 792
      registered participants, 84.4% (n = 669) received a blood test. Of the 669 tested
      participants, 7.9% (n = 53) tested HBV positive (HBsAg+, HBsAb -), 46.2% (n =
      309) were protected (HBsAg -, HBsAb +), and 45.9% (n = 307) were susceptible to
      HBV infection (HBsAg -, HBsAb -). Among those unprotected, 60% completed the
      vaccine series. Multivariate analysis showed that being Vietnamese (OR = 5.53,
      95% CI 1.54, 19.85), living in the US >10 years (OR = 2.12, 95% CI 1.13, 3.97),
      and having at least a college education (OR = 2.55, 95% CI 1.28, 5.07) were
      important predictors of vaccine completion. Given the various HBsAg + prevalence,
      screening, and vaccine completion rates among the different ethnic groups in this
      study, it is clear that different approaches in screening and vaccinating
      individual ethnic groups for hepatitis B are warranted.

PMID- 22362167
TI  - Adherence to and effectiveness of highly active antiretroviral treatment for HIV
      infection: assessing the bidirectional relationship.
AB  - BACKGROUND: It is well established that high adherence to HIV-infected patients
      on highly active antiretroviral treatment (HAART) is a major determinant of
      virological and immunologic success. Furthermore, psychosocial research has
      identified a wide range of adherence factors including patients' subjective
      beliefs about the effectiveness of HAART. Current statistical approaches, mainly
      based on the separate identification either of factors associated with treatment
      effectiveness or of those associated with adherence, fail to properly explore the
      true relationship between adherence and treatment effectiveness. Adherence
      behavior may be influenced not only by perceived benefits-which are usually the
      focus of related studies-but also by objective treatment benefits reflected in
      biological outcomes. METHODS: Our objective was to assess the bidirectional
      relationship between adherence and response to treatment among patients enrolled
      in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical
      approach based on the separate estimations of an adherence and an effectiveness
      equation to an econometric approach using a 2-equation simultaneous system based
      on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship
      between adherence and treatment effectiveness. After controlling for endogeneity,
      adherence was positively associated with treatment effectiveness. Furthermore,
      CD4 count gain after baseline was found to have a positive significant effect on
      adherence at each observation period. This immunologic parameter was not
      significant when the adherence equation was estimated separately. In the 2
      equation model, the covariances between disturbances of both equations were found
      to be significant, thus confirming the statistical appropriacy of studying
      adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which
      suggest that positive biological results arising as a result of high adherence
      levels, in turn reinforce continued adherence and strengthen the argument that
      patients who do not experience rapid improvement in their immunologic and
      clinical statuses after HAART initiation should be prioritized when developing
      adherence support interventions. Furthermore, they invalidate the hypothesis that
      HAART leads to "false reassurance" among HIV-infected patients.

PMID- 22362168
TI  - Bi-RADS category 3 nonpalpable breast masses on sonography: long-term results of
      a prospective cohort study.
AB  - PURPOSE: To determine the frequency of BI-RADS category 3 nonpalpable masses
      detected using only sonography (US) and the malignancy rate among these lesions.
      Second, to validate a proposed short-term follow-up regimen based on long-term
      observational results. METHODS: This prospective cohort study was conducted
      between September 2003 and April 2010. We conducted a 2-year short-term follow-up
      protocol composed of five US examinations at 3-month intervals for the first 6
      months, and at 6-month intervals for the next 18 months, followed with age
      appropriate screenings. Biopsy was recommended for the masses increasing in size
      and with changing imaging features. RESULTS: The frequency of category 3
      nonpalpable masses detected only on US in 11,373 consecutive women was 5.3%. Of
      562 lesions found in 451 women, 394 (70.1%) remained stable during the short-term
      and subsequent follow-up. Seventy-four (13.1%) masses showed interval regression
      and 79 (14.0%) showed interval progression. The malignancy rate was 0.3% (2 of
      562), with about 85% of interval changes occurring within the first 2 years. The
      negative predictive value of US in the detection of cancer was 99.6% (95% CI,
      98.7-99.9). The mean follow-up time was 65.5 +/- 8.7 months. CONCLUSIONS: The
      frequency of BI-RADS 3 nonpalpable masses detected using sonography alone was
      5.3%. During follow-up, the majority of interval changes occurred within the
      first 2 years. Because these masses have a very low malignancy rate, a 2-year
      follow-up instead of immediate biopsy is an appropriate option.

PMID- 22362169
TI  - A facile synthesis of cubic (Im3m) alumina films on glass with potential
      catalytic activity.
AB  - Thermally stable phase pure mesoporous cubic (Im3m) alumina films were
      synthesized on glass substrates under ambient conditions. These cubic alumina
      films incorporated with Au NPs exhibited excellent catalytic property.

PMID- 22362171
TI  - Degradation of 4-chlorophenol in aqueous solution photoinduced by Fe(III)-citrate
      complex.
AB  - The 4-chlorophenol (4-CP) degradation photoinduced by Fe(III)-citrate complex was
      investigated upon irradiation at 365 nm at different pHs (2.0, 3.0, 4.0 and 6.0).
      The best efficiency for 4-CP degradation in the presence of Fe(III)-citrate was
      at pH 3.0 with a value of quantum yield equal to 0.026. This effect is mainly
      attributed to speciation of Fe(III)-citrate complex which is very sensitive to
      the pH. Quantum yields of 4-CP degradation, Fe(III)-citrate disappearance and
      Fe(II) formation were carried out at wavelength 365 nm at different pHs (3.0 and
      6.0). The effect of the pH is less pronounced for the quantum yields of 4-CP than
      for Fe(III)-citrate complex and Fe(II) quantum yields which are species involved
      in the initial photochemical process. The effect of oxygen, isopropanol and
      Fe(III)-citrate concentrations on the quantum yields of 4-CP degradation and also
      on kinetics of 4-CP disappearance was also studied. Indeed, 4-CP requires the
      presence of oxygen to be degraded. The disappearance of 4-CP was totally
      inhibited without oxygen dissolved in the solution. Oxygen is essential for the
      formation of oxidative species and, as a consequence, for the degradation of the
      pollutant.

PMID- 22362172
TI  - Brother, have you got a light? Assessing the need for intubation in patients
      sustaining burn injury secondary to home oxygen therapy.
AB  - Home oxygen therapy use has steadily increased for the past 30 years. A majority
      of these patients suffer from chronic obstructive pulmonary disease secondary to
      smoking. Although warned of the danger of smoking while on oxygen, patients
      continue to do so, potentially resulting in cutaneous burns and suspected
      inhalation injury. Those suspected of inhalation injury are intubated for airway
      control. In the English literature, there is a paucity of data discussing the
      need for intubation. To date, this is the largest study to determine whether
      intubated patients had inhalation injury as observed by bronchoscopy and whether
      intubation was necessary. All patient's charts who sustained burns while on home
      oxygen therapy from May 2000 to May 2010 were retrospectively reviewed (n = 86).
      Data collected were age, sex, TBSA, ventilator days, length of stay (LOS), and
      presence or absence of inhalation. Of those patients intubated, a subset analysis
      was performed to determine whether intubation in the "Field" or "Outside
      Hospital" correlated with inhalation injury compared with intubation in our
      Emergency Department. Eighty-six patients (mean age 64 years, mean %TBSA 2.6)
      were included. Before transfer to the burn unit, 32 patients (37%) were intubated
      and 52 patients (61%) were not intubated. Of the 32 intubated patients,
      bronchoscopy confirmed inhalation injury in 12 patients (39%). No significant
      difference was seen in %TBSA between intubated vs nonintubated patients (3.5 vs
      2.0, respectively). However, there was a difference in LOS between the two groups
      (12.7 vs 2.8, respectively). No difference was found in incidence of inhalation
      injury between patients intubated in the "Field/Outside Hospital" compared with
      patients intubated in our Emergency Department (39% and 37.5%, respectively).
      Between the subgroups, no difference was found in %TBSA, ventilator days, or LOS.
      One patient admitted for airway observation required intubation and one patient
      failed extubation, postoperatively. Patients on home oxygen therapy suspected of
      inhalation injury should ideally be observed for signs of airway compromise
      before intubation is performed.

PMID- 22362173
TI  - Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid
      revascularization.
AB  - Impaired revascularization of transplanted islets is a critical problem that
      leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are
      known to aid neovascularization, we aimed to enhance islet engraftment by
      cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or
      without (islet-only group) human cord blood-derived EPCs, were transplanted into
      diabetic nude mice. The islet-EPC group reached euglycemia by ~11 days
      posttransplantation, whereas the islet-only group did not. Also, the islet-EPC
      group had a higher serum porcine insulin level than the islet-only group. Islets
      from the islet-EPC group were more rapidly revascularized at the early period of
      transplantation without increment of final capillary density at the fully
      revascularized graft. Enhanced revascularization rate in the islet-EPC group was
      mainly attributed to stimulating vascular endothelial growth factor-A production
      from the graft. The rapid revascularization by EPC cotransplantation led to
      better graft perfusion and recovery from hypoxia. EPC cotransplantation was also
      associated with greater beta-cell proliferation, probably by more basement
      membrane production and hepatocyte growth factor secretion. In conclusion,
      cotransplantation of EPCs and islets induces better islet engraftment by
      enhancing the rate of graft revascularization. These findings might provide a
      directly applicable tool to enhance the efficacy of islet transplantation in
      clinical practice.

PMID- 22362174
TI  - Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune
      diabetes in combination with anti-CD3.
AB  - We have previously developed a combination therapy (CT) using anti-CD3 monoclonal
      antibodies together with islet-(auto)antigen immunizations that can more
      efficiently reverse type 1 diabetes (T1D) than either entity alone. However,
      clinical translation of antigen-specific therapies in general is hampered by the
      lack of biomarkers that could be used to optimize the modalities of antigen
      delivery and to predict responders from nonresponders. To support the rapid
      identification of candidate biomarkers, we systematically evaluated multiple
      variables in a mathematical disease model. The in silico predictions were
      validated by subsequent laboratory data in NOD mice with T1D that received anti
      CD3/oral insulin CT. Our study shows that higher anti-insulin autoantibody levels
      at diagnosis can distinguish responders and nonresponders among recipients of CT
      exquisitely well. In addition, early posttreatment changes in proinflammatory
      cytokines were indicative of long-term remission. Coadministration of oral
      insulin improved and prolonged the therapeutic efficacy of anti-CD3 therapy, and
      long-term protection was achieved by maintaining elevated insulin-specific
      regulatory T cell numbers that efficiently lowered diabetogenic effector memory T
      cells. Our validation of preexisting autoantibodies as biomarkers to distinguish
      future responders from nonresponders among recipients of oral insulin provides a
      compelling and mechanistic rationale to more rapidly translate anti-CD3/oral
      insulin CT for human T1D.

PMID- 22362175
TI  - Resveratrol attenuates obesity-associated peripheral and central inflammation and
      improves memory deficit in mice fed a high-fat diet.
AB  - Obesity-induced diabetes is associated with chronic inflammation and is
      considered a risk factor for neurodegeneration. We tested the hypothesis that an
      AMP-activated protein kinase activator, resveratrol (RES), which is known to
      exert potent anti-inflammatory effects, would attenuate peripheral and central
      inflammation and improve memory deficit in mice fed a high-fat diet (HFD).
      C57BL/6J mice were fed an HFD or an HFD supplemented with RES for 20 weeks.
      Metabolic parameters in serum were evaluated, and Western blot analysis and
      immunohistochemistry in peripheral organs and brain were completed. We used the
      Morris water maze test to study the role of RES on memory function in HFD-treated
      mice. RES treatment reduced hepatic steatosis, macrophage infiltration, and
      insulin resistance in HFD-fed mice. In the hippocampus of HFD-fed mice, the
      protein levels of tumor necrosis factor-alpha and Iba-1 expression were reduced
      by RES treatment. Choline acetyltransferase was increased, and the
      phosphorylation of tau was decreased in the hippocampus of HFD-fed mice upon RES
      treatment. In particular, we found that RES significantly improved memory deficit
      in HFD-fed mice. These findings indicate that RES reverses obesity-related
      peripheral and central inflammation and metabolic derangements and improves
      memory deficit in HFD-fed diabetic mice.

PMID- 22362176
TI  - Hyperthermia with mild electrical stimulation protects pancreatic beta-cells from
      cell stresses and apoptosis.
AB  - Induction of heat shock protein (HSP) 72 improves metabolic profiles in diabetic
      model mice. However, its effect on pancreatic beta-cells is not known. The
      current study investigated whether HSP72 induction can reduce beta-cell stress
      signaling and apoptosis and preserve beta-cell mass. MIN6 cells and db/db mice
      were sham-treated or treated with heat shock (HS) and mild electrical stimulation
      (MES) (HS+MES) to induce HSP72. Several cellular markers, metabolic parameters,
      and beta-cell mass were evaluated. HS+MES treatment or HSP72 overexpression
      increased HSP72 protein levels and decreased tumor necrosis factor (TNF)-alpha
      induced Jun NH(2)-terminal kinase (JNK) phosphorylation, endoplasmic reticulum
      (ER) stress, and proapoptotic signal in MIN6 cells. In db/db mice, HS+MES
      treatment for 12 weeks significantly improved insulin sensitivity and glucose
      homeostasis. Upon glucose challenge, a significant increase in insulin secretion
      was observed in vivo. Compared with sham treatment, levels of HSP72, insulin,
      pancreatic duodenal homeobox-1, GLUT2, and insulin receptor substrate-2 were
      upregulated in the pancreatic islets of HS+MES-treated mice, whereas JNK
      phosphorylation, nuclear translocation of forkhead box class O-1, and nuclear
      factor-kappaB p65 were reduced. Apoptotic signals, ER stress, and oxidative
      stress markers were attenuated. Thus, HSP72 induction by HS+MES treatment
      protects beta-cells from apoptosis by attenuating JNK activation and cell
      stresses. HS+MES combination therapy may preserve pancreatic beta-cell volume to
      ameliorate glucose homeostasis in diabetes.

PMID- 22362177
TI  - Glycerol-treated nuclear suspensions--an efficient preservation method for flow
      cytometric analysis of plant samples.
AB  - Flow cytometry (FCM) has been widely used in plant science to determine the
      amount of nuclear DNA, either in absolute units or in relative terms, as an
      indicator of ploidy. The requirement for fresh material in some applications,
      however, limits the value of FCM in field research, including plant
      biosystematics, ecology and population biology. Dried plant samples have proven
      to be a suitable alternative in some cases (large-scale ploidy screening)
      although tissue dehydration is often associated with a decrease in the quality of
      FCM analysis. The present study tested, using time-scale laboratory and in situ
      field experiments, the applicability of glycerol-treated nuclear suspension for
      DNA flow cytometry. We demonstrate that plant nuclei preserved in ice-cold buffer
      + glycerol solution remain intact for at least a few weeks and provide estimates
      of nuclear DNA content that are highly comparable and of similar quality to those
      obtained from fresh tissue. The protocol is compatible with both DAPI and
      propidium iodide staining, and allows not only the determination of ploidy level
      but also genome size in absolute units. Despite its higher laboriousness,
      glycerol-preserved nuclei apparently represent the most reliable way of sample
      preservation for genome size research. We assume that the protocol will provide a
      vital alternative to other preservation methods, especially when stringent
      criteria on the quality of FCM analysis are required.

PMID- 22362178
TI  - Urothelial carcinoma of the renal pelvis with simultaneous trophoblastic and
      malignant clear cell endodermal-type differentiation.

PMID- 22362179
TI  - Highlights in NSCLC From the IASLC (International Association for the Study of
      Lung Cancer) 14th World Conference on Lung Cancer.

PMID- 22362180
TI  - [The image of the dentist. Part 1: Results of a literature search].
AB  - The dentist enjoys a high degree of professional independence. He is seen as
      reliable and productive at work while carrying a big responsibility. His foremost
      social responsibility is to treat patients suffering from toothache and to
      promote oral health prevention for all people, regardless of their social status.
      At the same time, the dentist is prestigious, respected and honest. Comparable to
      other professions, however, dentistry is under public pressure. Media often
      associate the dental profession with negative properties such as sadism,
      immorality, or madness. Does the image of the dental profession suffer in this
      context? Our first article discusses the environmental factors which are
      identifiable to influence both each dentist and ultimately the whole image of
      dentistry.

PMID- 22362182
TI  - Classification of test agent-specific effects in the Syrian hamster embryo assay
      (pH 6.7) using infrared spectroscopy with computational analysis.
AB  - The Syrian hamster embryo (SHE) cell transformation assay (pH 6.7) has utility in
      the assessment of potential chemical carcinogenicity (both genotoxic and non
      genotoxic mechanisms of action). The assay uses morphological transformation as
      an end point and has a reported sensitivity of 87%, specificity of 83% and
      overall concordance of 85% with in vivo rodent bioassay data. However, the
      scoring of morphologically transformed SHE cells is subjective. We treated SHE
      cells grown on low-E reflective slides with benzo[a]pyrene, 3-methylcholanthrene,
      anthracene, N-nitroso-N-methylnitroguanidine, ortho-toluidine HCl, 2,4
      diaminotoluene or D-mannitol for 7 days before fixation with methanol. Identified
      colonies were interrogated by acquiring a minimum of five infrared (IR) spectra
      per colony using attenuated total reflection Fourier-transform IR spectroscopy.
      Individual IR spectra were acquired over a spatial area of approximately 250 *
      250 MUm. Resultant data were analysed using Fisher's linear discriminant analysis
      and feature histogram algorithms to extract classifying biomarkers of test agent
      specific effects or transformation in SHE cells. Clustering of spectral points
      suggested co-segregation or discrimination of test agent categories based on
      mechanism of action. Towards transformation, unifying alterations were associated
      with alterations in the Amide I and Amide II peaks; these were consistently major
      classifying biomarkers for transformed versus non-transformed SHE cells. Our
      approach highlights a novel method towards objectively screening and classifying
      SHE cells, be it to ascertain test agent treatment based on mechanism of action
      or transformation.

PMID- 22362183
TI  - The mode of binding ACMA-DNA relies on the base-pair nature.
AB  - A thermodynamic and kinetic study on the mode of binding of 9-amino-6-chloro-2
      methoxi-acridine (ACMA) to poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC)
      has been undertaken at pH = 7.0 and I = 0.1 M. The spectrophotometric, kinetic (T
      jump), circular dichroism, viscometric and calorimetric information gathered
      point to formation of a fully intercalated ACMA complex with poly(dA-dT).poly(dA
      dT) and another one only partially intercalated (7%) with poly(dG-dC).poly(dG
      dC). The ACMA affinity with the A-T bases was higher than with the G-C bases. The
      two polynucleotide sequences give rise to external complexes when the ACMA
      concentration is raised, namely, the electrostatic complex poly(dA-dT).poly(dA
      dT)-ACMA and the major groove binding complex poly(dG-dC).poly(dG-dC)-ACMA. A
      considerable quenching effect of the ACMA fluorescence is observed with poly(dA
      dT).poly(dA-dT), ascribable to face-to-face location in the intercalated A-T-ACMA
      base-pairs. The even stronger effect observed in the presence of poly(dG
      dC).poly(dG-dC) is related to the guanine residue from on- and off-slot ACMA
      positions.

PMID- 22362181
TI  - Clinical, laboratory, and pacing predictors of CRT response.
AB  - A decade of research has established the role of cardiac resynchronization
      therapy (CRT) in medically refractory, moderate to severe systolic heart failure
      (HF) with intraventricular conduction delay. CRT is an electrical therapy
      instituted to reestablish ventricular synchronization in order to improve cardiac
      function and favorably modulate the neurohormonal system. CRT confers a mortality
      benefit, improved HF hospitalizations, and functional outcome in this population,
      but not all patients consistently demonstrate a positive CRT response. The
      nonresponder rate varies from 20% to 40%, depending on the defined response
      criteria. Efforts to improve response to CRT have focused on a number of fronts.
      Methods to optimize the correction of electrical and mechanical dyssynchrony,
      which is the primary target of CRT, has been the focus of research, in addition
      to improving patient selection and optimizing post-implant care. However, a major
      issue in dealing with improving nonresponse rates has been finding an accurate
      and generally accepted definition of "response" itself. The availability of a
      standard consensus definition of CRT response would enable the estimation of
      nonresponder burden accurately and permit the development of strategies to
      improve CRT response. In this review, we define various aspects of "response" to
      CRT and outline variability in the definition criteria and the problems with its
      inconsistencies. We describe clinical, laboratory, and pacing predictors that
      influence CRT response and outcome and how to optimize response.

PMID- 22362184
TI  - Role of oxidative stress in retinal photoreceptor cell death in N-methyl-N
      nitrosourea-treated mice.
AB  - This study aimed to investigate whether oxidative stress contributes to retinal
      cell death in a mouse model of photoreceptor degeneration induced by N-methyl-N
      nitrosourea (MNU). We measured in vitro MNU-induced radical production in retinal
      cell cultures of murine 661W photoreceptor-derived cells; RGC-5, a mouse ganglion
      cell line; and primary retinal cells. The addition of MNU induced oxidative
      radical generation in 661W and primary retinal cells, but not in RGC-5 cells.
      Edaravone, a free radical scavenger, at 1 uM reduced MNU-induced radical
      production in 661W and primary retinal cells. To induce in vivo retinal
      photoreceptor degeneration in mice, we administered 60 mg/kg MNU by
      intraperitoneal injection. We intravenously administered 1 mg/kg edaravone
      immediately and at 6 h after the MNU injection. Retinal photoreceptor
      degeneration was evaluated by measuring the thickness of the outer nuclear layer
      (ONL) by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      staining and by oxidative stress markers. MNU caused photoreceptor cell loss at 7
      days after administration. Edaravone inhibited ONL thinning and reduced TUNEL
      positive cells and the oxidative stress markers. These findings indicate that MNU
      leads to selective photoreceptor degradation via oxidative stress in vitro and in
      vivo and may help to understand the pathogenic mechanism of retinitis pigmentosa.

PMID- 22362185
TI  - A novel animal model of hearing loss caused by acute endoplasmic reticulum stress
      in the cochlea.
AB  - Many stimuli such as ischemia, hypoxia, heat shock, amino acid starvation, and
      gene mutation, exhibit a cellular response called endoplasmic reticulum (ER)
      stress. ER stress induces expression of a series of genes, leading to cell
      survival or apoptosis. Previously, we found that in an animal model of hearing
      loss caused by acute mitochondrial dysfunction, several ER stress markers
      including C/EBP homologous protein were induced in the cochlear lateral wall. To
      elucidate the mechanism of hearing loss caused by ER stress, we established a
      novel animal model of hearing loss by perilymphatic perfusion of tunicamycin, an
      ER stress activator that inhibits N-acetylglucosamine transferases. Subacute and
      progressive hearing loss was observed at all sound frequencies studied, and
      stimulation of ER stress marker genes was noted in the cochlea. The outer hair
      cells were the most sensitive to ER stress in the cochlea. Electron microscopic
      analysis demonstrated degeneration of the subcellular organelles of the inner
      hair cells and nerve endings of the spiral ganglion cells. This newly established
      animal model of hearing loss from ER stress will provide additional insight into
      the mechanism of sensorineural hearing loss.

PMID- 22362186
TI  - Effects of Roundup((r)) and glyphosate on three food microorganisms: Geotrichum
      candidum, Lactococcus lactis subsp. cremoris and Lactobacillus delbrueckii subsp.
      bulgaricus.
AB  - Use of many pesticide products poses the problem of their effects on environment
      and health. Amongst them, the effects of glyphosate with its adjuvants and its by
      products are regularly discussed. The aim of the present study was to shed light
      on the real impact on biodiversity and ecosystems of Roundup((r)), a major
      herbicide used worldwide, and the glyphosate it contains, by the study of their
      effects on growth and viability of microbial models, namely, on three food
      microorganisms (Geotrichum candidum, Lactococcus lactis subsp. cremoris and
      Lactobacillus delbrueckii subsp. bulgaricus) widely used as starters in
      traditional and industrial dairy technologies. The presented results evidence
      that Roundup((r)) has an inhibitory effect on microbial growth and a microbicide
      effect at lower concentrations than those recommended in agriculture.
      Interestingly, glyphosate at these levels has no significant effect on the three
      studied microorganisms. Our work is consistent with previous studies which
      demonstrated that the toxic effect of glyphosate was amplified by its formulation
      adjuvants on different human cells and other eukaryotic models. Moreover, these
      results should be considered in the understanding of the loss of
      microbiodiversity and microbial concentration observed in raw milk for many
      years.

PMID- 22362187
TI  - Absence of MU opioid receptor mRNA expression in astrocytes and microglia of rat
      spinal cord.
AB  - Cumulating evidence has demonstrated that MU opioid receptor (MOR) agonists
      promote spinal glial activation, lead to synthesis and release of proinflammatory
      cytokines and chemokines, and contribute to opioid-induced hyperalgesia and
      development of opioid tolerance and dependence. However, whether these MOR
      agonists directly or indirectly act on spinal cord astrocytes and microglial
      cells in vivo is unclear. In the present study, by combining the techniques of in
      situ hybridization of MOR mRNA with immunohistochemistry of glial fibrillary
      acidic protein (GFAP; an astrocyte marker) and Iba1 (a microglial marker), we
      examined expression and distribution of GFAP, Iba1, and MOR mRNA in the spinal
      cord of rats under chronic morphine tolerance conditions. Intrathecal injections
      of morphine twice daily for 7 days reduced morphine analgesic effect and
      increased both GFAP and Iba1 immunostaining densities in the spinal cord.
      Surprisingly, neither GFAP nor Iba1 colocalized with MOR mRNA in spinal cord
      cells. Our findings indicate that MOR expression is absent from spinal cord
      astrocytes and microglia, suggesting that these cell types are indirectly
      activated by MOR agonists under chronic opioid tolerance conditions.

PMID- 22362188
TI  - Recent progress on metal core@semiconductor shell nanocomposites as a promising
      type of photocatalyst.
AB  - The creation of core-shell nanocomposites (CSNs) has attracted considerable
      attention and developed into an increasingly important research area at the
      frontier of advanced materials chemistry. CSNs, which are nanoscaled assemblies
      with a chemical composition that is different on the surface compared to the core
      region, have found versatile applications in many fields, such as electrooptics,
      quantum dots, microscopy labels, drug delivery, chemical sensors, nanoreactors
      and catalysis. This review is primarily focused on the applications of metal
      core@semiconductor shell nanocomposites in heterogeneous photocatalysis,
      including photocatalytic nonselective processes for environmental remediation,
      selective organic transformations to fine chemicals and water splitting to clean
      hydrogen energy. It is hoped that this minireview can inspire multidisciplinary
      research interest in the precisely morphology-controlled synthesis of a variety
      of metal core@semiconductor shell nanoassemblies and their wide applications in
      the realm of heterogeneous photocatalysis.

PMID- 22362189
TI  - A general strategy for the experimental study of the thermochemistry of protic
      ionic liquids: enthalpy of formation and vaporisation of 1-methylimidazolium
      ethanoate.
AB  - A general strategy to determine enthalpies of formation of protic ionic liquids,
      based solely on enthalpy of solution measurements, was conceived and tested for 1
      methylimidazolium ethanoate, leading to Delta(f)H degrees (m){[Hmim][O(2)CCH(3)],
      1} = -(425.7 +/- 1.2) kJ mol(-1). This result in conjunction with the enthalpy of
      formation of gaseous 1-methylimidazole (mim) proposed in this work, Delta(f)H
      degrees (m)(mim, g) = 126.5 +/- 1.1 kJ mol(-1), and Delta(f)H degrees
      (m)(CH(3)COOH, g) taken from the literature, allowed the calculation of the
      enthalpy of the vaporisation process [Hmim][O(2)CCH(3)](l) -> mim(g) +
      CH(3)COOH(g) as Delta(vap)H degrees (m){[Hmim][O(2)CCH(3)]} = 119.4 +/- 3.0 kJ
      mol(-1). The agreement between this value and Delta(vap)H degrees
      (m){[Hmim][O(2)CCH(3)]} = 117.3 +/- 0.5 kJ mol(-1), obtained for the direct
      vaporisation of [Hmim][O(2)CCH(3)], by Calvet-drop microcalorimetry, gives a good
      indication that, as previously suggested by Fourier transform ion cyclotron
      resonance mass spectrometry, Raman spectroscopy, and GC-MS experiments, the
      vaporisation of [Hmim][O(2)CCH(3)] essentially involves a proton transfer
      mechanism with formation of the two volatile neutral precursor molecules (mim and
      CH(3)COOH). Although being a low ionicity protic ionic liquid, [Hmim][O(2)CCH(3)]
      was chosen to validate the methodology proposed here, since its vaporisation
      mechanism has been unequivocally demonstrated by different methods and for
      different pressure ranges.

PMID- 22362190
TI  - Effect of high-dose methotrexate chemotherapy on intestinal Bifidobacteria,
      Lactobacillus and Escherichia coli in children with acute lymphoblastic leukemia.
AB  - High-dose methotrexate (HDMTX) chemotherapy is generally accepted as an effective
      method for the treatment and prevention of extramedullary leukemia in children.
      However, it is unknown whether HDMTX chemotherapy kills intestinal bacteria on a
      large scale, thus causing dysbacteriosis, which may in turn influence the
      progress or prognosis of leukemia. The aim of this study was to examine changes
      in intestinal flora in children with acute lymphoblastic leukemia (ALL) treated
      with HDMTX chemotherapy. Bacterial DNA in stool from 36 healthy children and 36
      ALL children were tested at A(260) with a spectrophotometer before and after
      HDMTX chemotherapy. The primers of Bifidobacteria, Lactobacillus and Escherichia
      coli were designed according to the 16SrRNA/DNA bacterial sequences. Bacteria
      were qualitatively and quantitatively confirmed by routine polymerase chain
      reaction (PCR) and fluorescent quantitative PCR, respectively. Our data showed
      that the total amount of flora in the stools of children with ALL was decreased
      by 29.6% compared with healthy children (P < 0.01). The total amount of flora in
      the stools of children with ALL on the third and seventh days after chemotherapy
      were 1496.5 +/- 577.1 and 1966.6 +/- 598.3 ng/MUL, respectively, which was
      notably less than before chemotherapy (2436.3 +/- 768.6 ng/MUL). The amount of
      Bifidobacteria, Lactobacillus and E. coli in the intestinal tract in the ALL
      group after chemotherapy had an apparent change, which decreased most clearly on
      the third day, and partially recovered on the seventh day after chemotherapy.
      HDMTX chemotherapy can cause intestinal dysbacteriosis in children with ALL. The
      amount of Bifidobacteria, Lactobacillus and E. coli decreased significantly
      compared with the control group.

PMID- 22362191
TI  - Prenatal diagnosis and management of congenital chloride diarrhea: A case report
      of 2 siblings.
AB  - Congenital chloride diarrhea (CLD) is a rare hereditary disease. The basic defect
      of CLD is massive loss of Cl(-) and fluid into the ileum and colon. Prenatal
      diagnosis of this disease is quite important because the infant requires
      electrolyte supplementation from the early postnatal period. Two cases in which
      prenatal diagnoses of CLD were made in siblings are reported. Extreme electrolyte
      imbalance may cause fetal cardiac dysfunction or a poor general condition leading
      to a non-reassuring fetal status in cases with CLD. Therefore, frequent fetal
      monitoring using cardiotocograms and ultrasound may be beneficial to some fetuses
      with CLD to detect fetal deterioration. In addition, repeated amnioreduction may
      be required to treat severe polyhydramnios and threatened preterm delivery.

PMID- 22362192
TI  - Long-term results of a cardiovascular implantable electronic device wrapped with
      an expanded polytetrafluoroethylene sheet.
AB  - The use of an expanded polytetrafluoroethylene (ePTFE) sheet wrapping device for
      patients with pacemaker contact dermatitis is still controversial. This study
      aimed to retrospectively investigate the occurrence rate of allergies and other
      complications after implantation of a cardiovascular implantable electronic
      device (CIED) wrapped with an ePTFE sheet. A total of 4,497 procedures of CIED
      implantation were performed at our institution between January 1993 and April
      2010. Among 19 patients who underwent implantation of an electronic cardiac
      device wrapped with an ePTFE sheet, device implantation was performed in 11
      patients for secondary prevention of device contact sensitivity, in 7 patients
      for primary prevention of device contact sensitivity, and in 1 patient for
      avoiding over-sensing of myopotentials. During follow-up periods (mean 46 +/- 34
      months), there were no allergic or inflammatory reactions to components of the
      device or ePTFE itself. Among 11 patients with a device wrapped with an ePTFE
      sheet for secondary prevention, 5 patients completed device replacement due to
      battery depletion and 3 patients had infections from the device. Wrapping
      implantable devices with an ePTFE sheet is an effective way of preventing device
      sensitivity in patients who require CIED therapy. However, the risk of infection
      from the device should be taken into consideration.

PMID- 22362193
TI  - Augmentation of CPD photolyase activity in japonica and indica rice increases
      their UVB resistance but still leaves the difference in their sensitivities.
AB  - Rice cultivars vary widely in their sensitivity to ultraviolet B (UVB, 280-320
      nm). Specifically, many indica rice cultivars from tropical regions, where UVB
      radiation is higher, are hypersensitive to UVB. Photoreactivation mediated by the
      photolyase enzyme is the major pathway for repairing UVB-induced cyclobutane
      pyrimidine dimers (CPDs) in plants. Still, these UVB-sensitive cultivars are less
      able to repair CPDs through photoreactivation than UVB-resistant cultivars. Here,
      we produced CPD photolyase-overexpressing transgenic rice plants with higher CPD
      photolyase activity using UVB-sensitive rice Norin 1 (japonica) and UVB
      hypersensitive rice Surjamkhi (indica) as parental line (PL) plants. The results
      show that these transgenic rice plants were much more resistant to UVB-induced
      growth inhibition than were PL cultivars. The present findings strongly indicate
      that UVB-resistance, caused by an increase in CPD photolyase activity, can be
      achieved in various rice cultivars. However, there was a difference in the level
      of reduction of UVB-induced growth inhibition among rice cultivars; the level of
      reduction of growth inhibition in transgenic rice plants generated from the
      indica strain was lower than that of transgenic rice plants generated from
      japonica strains. These results indicate that the growth of the UVB
      hypersensitive indica strain was strongly inhibited by other factors in addition
      to CPD levels. 

PMID- 22362195
TI  - Haitian adolescent personality clusters and their problem area correlates.
AB  - This study identified personality clusters among a community sample of
      adolescents of Haitian decent and related cluster subgroup membership to problems
      in the areas of substance abuse, mental and physical health, family and peer
      relationships, educational and vocational status, social skills, leisure and
      recreational pursuits, aggressive behavior-delinquency, and to sexual risk
      activity. Three cluster subgroups were identified: dependent/conforming (N = 68),
      high pathology (N = 30); and confident/extroverted/conforming (N = 111). Although
      the overall sample was relatively healthy based on low average endorsement of
      problems across areas of expressed concern, significant physical health, mental
      health, relationship, educational, and HIV risk problems were identified in a
      MACI identified high psychopathology cluster subgroup. A
      confident/extraverted/conforming cluster subgroup revealed few problems and
      appears to reflect a protective style.

PMID- 22362194
TI  - Role of central angiotensin receptors in scopolamine-induced impairment in
      memory, cerebral blood flow, and cholinergic function.
AB  - RATIONAL: Inhibition of renin-angiotensin system (RAS) improves cognitive
      functions in hypertensive patients. However, role of AT1 and AT2 receptors in
      memory impairment due to cholinergic hypofunction is unexplored. OBJECTIVE: This
      study investigated the role of AT1 and AT2 receptors in cerebral blood flow
      (CBF), cholinergic neurotransmission, and cerebral energy metabolism in
      scopolamine-induced amnesic mice. METHODS: Scopolamine was given to male Swiss
      albino mice to induce memory impairment tested in passive avoidance and Morris
      water maze tests after a week long administration of blocker of AT1 receptor,
      candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler
      flowmetry. Biochemical and molecular studies were done in cortex and hippocampus
      of mice brain. RESULTS: Scopolamine caused memory impairment, reduced CBF,
      acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and
      malondialdehyde (MDA). Administration of vehicle had no significant effect on any
      parameter in comparison to control. Candesartan prevented scopolamine-induced
      amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level.
      In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor
      blocker on memory, CBF, ACh level, and oxidative stress was blunted by
      concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE)
      activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered.
      CONCLUSION: The study suggests that activation of AT1 receptors appears to be
      involved in the scopolamine-induced amnesia and that AT2 receptors contribute to
      the beneficial effects of candesartan. Theses finding corroborated the number of
      clinical studies that RAS inhibition in hypertensive patients could be
      neuroprotective.

PMID- 22362196
TI  - Template-mediated synthesis and bio-functionalization of flexible lignin-based
      nanotubes and nanowires.
AB  - Limitations of cylindrical carbon nanotubes based on the buckminsterfullerene
      structure as delivery vehicles for therapeutic agents include their chemical
      inertness, sharp edges and toxicological concerns. As an alternative, we have
      developed lignin-based nanotubes synthesized in a sacrificial template of
      commercially available alumina membranes. Lignin is a complex phenolic plant cell
      wall polymer that is generated as a waste product from paper mills and
      biorefineries that process lignocellulosic biomass into fuels and chemicals. We
      covalently linked isolated lignin to the inner walls of activated alumina
      membranes and then added layers of dehydrogenation polymer onto this base layer
      via a peroxidase-catalyzed reaction. By using phenolic monomers displaying
      different reactivities, we were able to change the thickness of the polymer layer
      deposited within the pores, resulting in the synthesis of nanotubes with a wall
      thickness of approximately 15 nm or nanowires with a nominal diameter of 200 nm.
      These novel nanotubes are flexible and can be bio-functionalized easily and
      specifically, as shown by in vitro assays with biotin and Concanavalin A.
      Together with their intrinsic optical properties, which can also be varied as a
      function of their chemical composition, these lignin-based nanotubes are expected
      to enable a variety of new applications including as delivery systems that can be
      easily localized and imaged after uptake by living cells.

PMID- 22362197
TI  - [Which diabetes education program does achieve the best results?].

PMID- 22362198
TI  - Efficient semiparametric mean-association estimation for longitudinal binary
      responses.
AB  - Semiparametric methods for longitudinal data with association within subjects
      have recently received considerable attention. However, existing methods for
      semiparametric longitudinal binary regression modeling (i) mainly concern mean
      structures with association parameters treated as nuisance; (ii) generally
      require a correct specification of the covariance structure for misspecified
      covariance structure may lead to inefficient mean parameter estimates; and (iii)
      usually run into computation and estimation problems when the time points are
      irregularly and possibly subject specific. In this article, we propose a
      semiparametric logistic regression model, which simultaneously takes into account
      both the mean and response-association structures (via conditional log-odds
      ratio) for multivariate longitudinal binary outcomes. Our main interest lies in
      efficient estimation of both the marginal and association parameters. The
      estimators of the parameters are obtained via the profile kernel approach. We
      evaluate the proposed methodology through simulation studies and apply it to a
      real dataset. Both theoretical and empirical results demonstrate that the
      proposed method yields highly efficient estimators and performs satisfactorily.

PMID- 22362199
TI  - Evacetrapib.
AB  - Considerable attention focuses on the ability to develop therapeutic agents that
      elevate levels of high-density lipoprotein cholesterol (HDL-C). Cholesteryl ester
      transfer protein (CETP) inhibitors have been developed on the basis of their
      ability to raise HDL-C to a greater extent than lipid-modifying therapies
      currently used in clinical practice. Initial enthusiasm for CETP inhibition
      decreased as a result of adverse clinical outcomes observed with the agent
      torcetrapib. Elucidating off-target toxicities of torcetrapib has provided hope
      that other CETP inhibitors may still be of potential benefit. Evacetrapib is a
      novel CETP inhibitor, with favorable effects on plasma lipids and no adverse
      effects on blood pressure or mineralocorticoid activity in early clinical
      evaluation. The potential effects on cardiovascular outcomes remain to be
      determined.

PMID- 22362201
TI  - Common and distinct neural inputs to the medial central nucleus of the amygdala
      and anterior ventrolateral bed nucleus of stria terminalis in rats.
AB  - The central nucleus of the amygdala (CEA) and lateral bed nucleus of stria
      terminalis (BST) are highly interconnected limbic forebrain regions that share
      similar connectivity with other brain regions that coordinate behavioral and
      physiological responses to internal and environmental stressors. Their similar
      connectivity is frequently referred to when describing the CEA and lateral BST
      together as a unified "central extended amygdala". However, the CEA and BST
      reportedly play distinct roles in behavioral and physiological responses
      associated with fear, anxiety, and social defeat, presumably due to differences
      in connectivity. To identify common and unique sources of input to the CEA and
      lateral BST, we performed dual retrograde tracing. Fluorogold and cholera toxin
      beta were iontophoresed into the medial CEA (CEAm) and the anterior ventrolateral
      BST (BSTvl) of adult male rats. The anatomical distribution of tracer-labeled
      neurons was mapped throughout the brain. Regions with overlapping populations of
      CEAm- and BSTvl-projecting neurons were further examined for the presence of
      double-labeled neurons. Although most regions with input to the mCEA also
      projected to the BSTvl, and vice versa, cortical and sensory system-related
      regions projected more robustly to the CEAm, while motor system-related regions
      primarily innervated the BSTvl. The incidence of double-labeled neurons with
      collateralized axonal inputs to the CEAm and BSTvl was relatively small (~2 to
      13%) and varied across regions, suggesting regional differences in the degree of
      coordinated CEAm and BSTvl input. The demonstrated similarities and differences
      in inputs to CEAm and BSTvl provide new anatomical insights into the functional
      organization of these limbic forebrain regions.

PMID- 22362202
TI  - Musculotopic organization of the motor neurons supplying forelimb and shoulder
      girdle muscles in the mouse.
AB  - We identified the motor neurons (MNs) supplying the shoulder girdle and forelimb
      muscles in the C57BL/6J mouse spinal cord using Fluoro-Gold retrograde tracer
      injections. In spinal cord transverse sections from C2 to T2, we observed two MN
      columns (medial and lateral) both with ventral and dorsal subdivisions. The
      dorsolateral column consisted of the biceps brachii, forearm extensors, forearm
      flexors, and hand MNs, and the ventrolateral column consisted of the latissimus
      dorsi, trapezius, teres major, deltoid, and triceps MNs. The supraspinatus muscle
      MNs were located in the dorsomedial column, and pectoralis major and serratus
      anterior MNs were located in the ventromedial columns. MNs of the dorsolateral
      column innervated the biceps brachii in mid-C4 to mid-C7, forearm extensors in
      caudal C4 to mid-T1, forearm flexors in rostral C5 to mid-T1, and hand muscles in
      mid-C8 to mid-T2 segments. The MNs innervating the trapezius were located in mid
      C2 to mid-C4, triceps brachii in mid-C6 to rostral T1, deltoid in rostral C4 to
      mid-C6, teres major in rostral C5 to mid-C8, and latissimus dorsi in mid-C5 to
      caudal C8. In addition, MNs innervating the supraspinatus were located from
      rostral C4 to caudal C8, pectoralis major in mid-C6 to mid-T2, and serratus
      anterior in rostral C5 to caudal C7/rostral C8 segments. While the musculotopic
      pattern of MN groups was very similar to that documented for other species, we
      found differences in the position and cranio-caudal extent of some MN pools
      compared with previous reports. The identification of mouse forelimb MNs can
      serve as an anatomical reference for studying degenerative MN diseases, spinal
      cord injury, and developmental gene expression.

PMID- 22362200
TI  - Structure-function relationship of working memory activity with hippocampal and
      prefrontal cortex volumes.
AB  - A rapidly increasing number of studies are quantifying the system-level network
      architecture of the human brain based on structural-to-structural and functional
      to-functional relationships. However, a largely unexplored area is the nature and
      existence of "cross-modal" structural-functional relationships, in which, for
      example, the volume (or other morphological property) of one brain region is
      related to the functional response to a given task either in that same brain
      region, or another brain region. The present study investigated whether the gray
      matter volume of a selected group of structures (superior, middle, and inferior
      frontal gyri, thalamus, and hippocampus) was correlated with the fMRI response to
      a working memory task, within a mask of regions previously identified as involved
      with working memory. The subjects included individuals with schizophrenia, their
      siblings, and healthy controls (n = 154 total). Using rigorous permutation
      testing to define the null distribution, we found that the volume of the superior
      and middle frontal gyri was correlated with working memory activity within
      clusters in the intraparietal sulcus (i.e., dorsal parietal cortex) and that the
      volume of the hippocampus was correlated with working memory activity within
      clusters in the dorsal anterior cingulate cortex and left inferior frontal gyrus.
      However, we did not find evidence that the identified structure-function
      relationships differed between subject groups. These results show that long
      distance structural-functional relationships exist within the human brain. The
      study of such cross-modal relationships represents an additional approach for
      studying systems-level interregional brain networks.

PMID- 22362203
TI  - Experiences of school bullying among internationally adopted children: results
      from the Finnish Adoption (FINADO) Study.
AB  - This study investigated the prevalence of and factors associated with school
      bullying and victimization among Finnish international adoptees. The Olweus
      bully/victim questionnaire was sent to all 9-15-year-old children adopted in
      Finland between 1985 and 2007 through the mediating organizations officially
      approved by the Ministry of Social Affairs and Health. The children were
      identified through official adoption organizations. The response rate in the
      target sample was 49.4%: the study sample consisted of 364 children (190 girls,
      52.2%). The children's background factors and symptoms of reactive attachment
      disorder (RAD) were evaluated using a FINADO questionnaire. Their learning
      difficulties and social and language skills were assessed using a standardized
      parental questionnaire (Five to Fifteen). Of the participants, 19.8% reported
      victimization by peers while 8% had bullied others. Both victimization and
      bullying were associated with severe symptoms of RAD at the time of adoption (RR
      2.68, 95%CI 1.50-4.77 and RR 2.08, 95%CI 1.17-3.69 for victimization and
      bullying, respectively). Lack of social skills was associated with victimization
      (RR 1.74, 95%CI 1.06-2.85) but not independently with being a bully (RR 1.50,
      95%CI 0.91-2.45). In a multivariate analysis the child's learning difficulties
      and language difficulties were not associated with either bullying others or
      victimization.

PMID- 22362204
TI  - Background current reduction and biobarcode amplification for label-free, highly
      sensitive electrochemical detection of pathogenic DNA.
AB  - By using exonuclease I and biobarcode nanoparticles, we describe a novel
      background current reduction strategy for amplified electrochemical detection of
      uropathogen specific sequences at ultralow concentrations.

PMID- 22362205
TI  - Enforced compliance.

PMID- 22362209
TI  - Scheduled delivery.

PMID- 22362210
TI  - Oncogenic morphs of p53.

PMID- 22362212
TI  - Histone modification at the gene level.

PMID- 22362217
TI  - Altered gene expression profiles in mouse tetraploid blastocysts.
AB  - In this study, it was demonstrated that tetraploid-derived blastocyst embryos had
      very few Oct4-positive cells at the mid-blastocyst stage and that the inner cell
      mass at biomarkers Oct4, Sox2 and Klf4 was expressed at less than 10% of the
      level observed in diploid blastocysts. In contrast, trophectoderm-related gene
      transcripts showed an approximately 10 to 40% increase. Of 32,996 individual
      mouse genes evaluated by microarray, 50 genes were differentially expressed
      between tetraploid or diploid and parthenote embryos at the blastocyst stage
      (P<0.05). Of these 50 genes, 28 were more highly expressed in tetraploid-derived
      blastocysts, whereas 22 were more highly downregulated. However, some genes
      involved in receptor activity, cell adhesion molecule, calcium ion binding,
      protein biosynthesis, redox processes, transport, and transcription showed a
      significant decrease or increase in gene expression in the tetraploid-derived
      blastocyst embryos. Thus, microarray analysis can be used as a tool to screen for
      underlying defects responsible for the development of tetraploid-derived embryos.

PMID- 22362215
TI  - Epithelial stem cells, wound healing and cancer.
AB  - It is well established that tissue repair depends on stem cells and that chronic
      wounds predispose to tumour formation. However, the association between stem
      cells, wound healing and cancer is poorly understood. Lineage tracing has now
      shown how stem cells are mobilized to repair skin wounds and how they contribute
      to skin tumour development. The signalling pathways, including WNT and Hedgehog,
      that control stem cell behaviour during wound healing are also implicated in
      tumour formation. Furthermore, tumorigenesis and wound repair both depend on
      communication between epithelial cells, mesenchymal cells and bone marrow-derived
      cells. These studies suggest ways to harness stem cells for wound repair while
      minimizing cancer risk.

PMID- 22362216
TI  - Lymphatic and interstitial flow in the tumour microenvironment: linking
      mechanobiology with immunity.
AB  - Tumours often engage the lymphatic system in order to invade and metastasize. The
      tumour-draining lymph node may be an immune-privileged site that protects the
      tumour from host immunity, and lymph flow that drains tumours is often increased,
      enhancing communication between the tumour and the sentinel node. In addition to
      increasing the transport of tumour antigens and regulatory cytokines to the lymph
      node, increased lymph flow in the tumour margin causes mechanical stress-induced
      changes in stromal cells that stiffen the matrix and alter the immune
      microenvironment of the tumour. We propose that synergies between lymphatic
      drainage and flow-induced mechanotransduction in the stroma promote tumour immune
      escape by appropriating lymphatic mechanisms of peripheral tolerance.

PMID- 22362218
TI  - Functional characterization of double-knockout mouse sperm lacking SPAM1 and ACR
      or SPAM1 and PRSS21 in fertilization.
AB  - Mammalian fertilization requires sperm to penetrate the cumulus to reach the
      oocyte. Although sperm hyaluronidase has long been believed to participate in the
      penetration process, our previous works revealed that neither of two sperm
      hyaluronidases, SPAM1 and HYAL5, are essential for fertilization. In this study,
      we have produced double-knockout mice lacking SPAM1 and either one of two sperm
      serine proteases, ACR and PRSS21, and characterized the mutant sperm. The
      SPAM1/ACR- and SPAM1/PRSS21-deficient males were fertile, whereas epididymal
      sperm of the mutant mice exhibited a reduced capacity to fertilize the oocytes in
      vitro. Despite normal motility, the ability of sperm to traverse the cumulus
      matrix was more severely impaired by the loss of SPAM1 and ACR or SPAM1 and
      PRSS21 than by the loss of only SPAM1. Moreover, SPAM1/ACR- and SPAM1/PRSS21
      deficient sperm accumulated on the surface (outer edge) of the cumulus more
      abundantly than SPAM1-deficient sperm. These results suggest that ACR or PRSS21
      or both may function cooperatively with SPAM1 in sperm/cumulus penetration.

PMID- 22362219
TI  - Clinical relevance of Ki67 gene expression analysis using formalin-fixed paraffin
      embedded breast cancer specimens.
AB  - BACKGROUND: Ki67 is a protein associated with cell cycle activity and shows a
      good correlation with the growth fraction, which has been proposed as a
      prognostic or predictive marker in breast cancer. In this study, we aimed to
      analyze the expression levels of Ki67 (MKI67) messenger RNA (mRNA) derived from
      formalin-fixed paraffin-embedded (FFPE) tissues for comparison with the
      immunohistochemical Ki67 labeling index, and investigate the correlation
      coefficients with clinical outcomes. METHODS: We analyzed the data of Ki67 mRNA
      from FFPE and matched fresh-frozen (FF) tissues based on a real-time quantitative
      reverse-transcription polymerase chain reaction (RT-qPCR) assay system in 203
      cases of primary invasive breast cancer. RESULTS: The correlation between Ki67
      mRNA expression of either FFPE or FF specimens and Ki67 labeling index was
      positive, as was the correlation between the FFPE and FF results (P < 0.0001).
      Ki67 mRNA expression of FFPE specimens was significantly associated with
      clinicopathological characteristics: tumor size, lymph node status, nuclear
      grade, hormone receptors, human epidermal growth factor receptor 2 (Her2) status,
      and tumor subtype. In prognostic results, Ki67 gene expression in the FFPE
      specimens revealed almost similar patterns of significance in Kaplan-Meier curves
      and univariate and multivariate relapse-free survival results as the Ki67
      labeling index. CONCLUSIONS: Gene expression analysis of Ki67 of FFPE specimens
      could be successfully performed using RT-qPCR, closely resembling the significant
      clinical characteristics of Ki67 labeling index. These results confirm that Ki67
      gene expression of FFPE specimens has potential for evaluation of cell cycle
      activity of breast cancer specimens.

PMID- 22362220
TI  - Spectroscopic selection of distance measurements in a protein dimer with mixed
      nitroxide and Gd3+ spin labels.
AB  - The pulse DEER (Double Electron-Electron Resonance) technique is frequently
      applied for measuring nanometer distances between specific sites in biological
      macromolecules. In this work we extend the applicability of this method to high
      field distance measurements in a protein assembly with mixed spin labels, i.e. a
      nitroxide spin label and a Gd(3+) tag. We demonstrate the possibility of
      spectroscopic selection of distance distributions between two nitroxide spin
      labels, a nitroxide spin label and a Gd(3+) ion, and two Gd(3+) ions. Gd(3+)
      nitroxide DEER measurements possess high potential for W-band long range distance
      measurements (6 nm) by combining high sensitivity with ease of data analysis,
      subject to some instrumental improvements.

PMID- 22362221
TI  - Evaluation of a cone beam CT artefact reduction algorithm.
AB  - OBJECTIVES: An algorithm and software to reduce metal artefact has been developed
      recently and is available in the Picasso Master 3D(r) (VATECH, Hwaseong, Republic
      of Korea), which under visual assessment produces better quality images than were
      obtainable previously. The objective of this in vitro study was to investigate
      whether the metal artefact reduction (MAR) algorithm of the Picasso Master 3D
      machine reduced the incidence of metal artefacts and increased the contrast-to
      noise ratio (CNR) while maintaining the same gray value when there was no
      metallic body present within the scanned volume. METHODS: 20 scans with a range
      of 50-90 kVp were acquired, of which 10 had a metallic bead inserted within a
      phantom. The images obtained were analysed using public domain software (ImageJ;
      NIH Image, Bethesda, MD). Area histograms were used to evaluate the mean gray
      level variation of the epoxy resin-based substitute (ERBS) block and a control
      area. The CNR was calculated. RESULTS: The MAR algorithm increased the CNR when
      the metallic bead was present; it enhanced the ERBS gray level independently of
      the presence of the metallic bead. The image quality also improved as peak tube
      potential was increased. CONCLUSION: Improved quality of images and regaining of
      the control gray values of a phantom were achieved when the MAR algorithm was
      used in the presence of a metallic bead.

PMID- 22362222
TI  - Nano-scaling law: geometric foundation of thiolated gold nanomolecules.
AB  - Thiolated gold nanomolecules show a power correlation between the number of gold
      atoms and the thiolate ligands with a 2/3 scaling similar to Platonic and
      Archimedean solids. Nanomolecule stability is influenced by a universal geometric
      factor that is foundational to its stability through the Euclidean surface rule,
      in addition to the electronic shell closing factor and staple motif requirements.

PMID- 22362223
TI  - Effect of annual endoscopic screening on clinicopathologic characteristics and
      treatment modality of gastric cancer in a high-incidence region of Korea.
AB  - We investigated risk factors for gastric cancer (GC) and effect of annual
      endoscopic screening on detection and treatment modality of GC. Asymptomatic
      adults who underwent upper endoscopy during health checkups at Seoul National
      University Hospital Healthcare System Gangnam Center were enrolled. We compared
      clinicopathologic characteristics of GC according to screening interval (repeated
      vs. infrequent, annual vs. biennial). After age- and sex-matching, relative risk
      was computed by hazard ratio (HR) using Cox proportional regression with
      multivariate adjustment. Of the 58,849 subjects who received screening endoscopy,
      277 (0.47%) were found to have GC. Intestinal type comprised 55.4% (102/184)
      followed by diffuse type (n = 65, 35.3%). Age >= 50 years, family history and
      smoking independently increased the risk of GC for both types, whereas male
      gender [HR = 4.81, 95% confidence interval (CI): 2.72-8.03] and intestinal
      metaplasia (IM) (HR = 10.87, 95% CI: 3.36-22.30) were significant predictors for
      intestinal type only. Proportion of early gastric cancer (EGC) was 98.6% (71/72)
      in annual screening group and 80.7% (46/57) in biennial screening group (p <
      0.01). In the former, tumor size was smaller (1.7 +/- 1.3 vs. 2.3 +/- 1.8 cm; p <
      0.01] and proportion of intramucosal cancer was larger (75.0 vs. 56.1%; p =
      0.04). Endoscopic resection was performed more frequently in annual screening
      group (56.9 vs. 33.3%; p = 0.02). IM along with male gender and older age was a
      strong risk factor for intestinal type GC. Annual screening group improved
      detection of early-stage and endoscopically treatable GC suggesting that
      intensive screening and surveillance may be useful for high-risk subpopulations
      with epidemiologic risk factors or premalignant lesions such as IM.

PMID- 22362224
TI  - Highlights from the Pan Pacific Lymphoma Conference. August 15-19, 2011, Kauai,
      Hawaii.

PMID- 22362225
TI  - Sonographic appearance of intrathyroid ectopic thymus in children.
AB  - PURPOSE: The aim of this study is to report the common location of intrathyroid
      ectopic thymus and describe the corresponding sonographic appearances in
      children. METHODS: We retrospectively reviewed clinical data and neck or thyroid
      ultrasonography (US) findings in children from January 2003 to May 2010.
      Intrathyroid lesions showing hypoechogenicity with multiple linear echogenic
      branching structures or punctate echogenic foci were considered intrathyroid
      ectopic thymus. US features of the lesions (location, side, size, and shape) and
      the indication for US were recorded. RESULTS: A total of 5,414 neck or thyroid US
      examinations were conducted in 3,195 children. We found 15 lesions that were
      suspected of being intrathyroid ectopic thymus in 12 patients (0.4%), four boys
      and eight girls, with a mean age of 6.4 years. The lesions were unilateral in
      nine patients and bilateral in three patients. All the lesions were located at
      the mid to lower portion of the thyroid. The long-axis diameter of the lesions
      ranged from 0.7 to 2.2 cm (mean diameter: 1.5 cm). All lesions had a fusiform
      shape with well-defined margins. CONCLUSIONS: The possibility of intrathyroid
      ectopic thymus should be considered when a mid- to low-lying intrathyroid lesion
      with a fusiform shape with multiple linear or punctate internal echoes is
      detected on US in children.

PMID- 22362226
TI  - Pulmonary fissures and lobes: a cadaveric study with emphasis on surgical and
      radiological implications.
AB  - PURPOSE: The objective was to study the morphology of fissures and lobes of the
      lung in South Indian population. MATERIALS AND METHODS: The study included 60
      adult cadaveric lungs which were obtained from the human anatomy laboratory. The
      specimens were macroscopically observed for gross morphology of fissures and
      lobes. RESULTS: Only 32 (53.3%) lungs showed the fissures and lobes as described
      in the standard anatomy texts. Among the right lungs, 15 (46.9%) had incomplete
      horizontal fissure, 6 lungs (18.7%) had absence of the horizontal fissure and one
      lung (3.1%) had the azygous lobe. The remaining 10 right lungs (31.3%) showed the
      usual morphology. In the left lungs, normal morphology was observed in 22 cases
      (78.6%), 2 lungs had incomplete oblique fissure (7.1%), one lung had (3.6%)
      absence of the oblique fissure, one lung showed an accessory fissure and lobe
      (3.6%). The anomalous multiple fissures and lobar pattern was observed in 2 cases
      (7.1%). CONCLUSION: Morphological knowledge of fissures and lobes of the lung is
      of importance to the thoracic surgeons in performing lobectomies and segmental
      resection. The radiologists should have an idea about these variations in
      interpreting the MRI and CT scans. We believe that the data from the present
      study certainly adds an important reference in the medical literature.

PMID- 22362227
TI  - [Is viscoelastic the corneal tissue?].
AB  - PURPOSE: To compare the known viscoelastic properties of soft tissues with
      singular published observations on the behaviour of corneal tissue. MATERIALS AND
      METHODS: The behaviour of the maxwellian element, typical viscoelastic
      biomechanical model, is compared with that of various previously studied soft
      tissues of animals. The same comparison can be made between stress-strain curves
      of riboflavin and UVA treated and untreated strips of human and porcine corneal
      tissue, stretched at constant velocity, from the literature. RESULTS: The
      asymptotic stress-strain curves of the various soft tissues previously examined
      could be faithfully simulated by the Maxwell viscoelastic element. The
      exponential stress-strain curves of samples of corneal tissue were clearly
      different. CONCLUSIONS: The observed divergence demonstrates incompatibility
      between the alleged behaviour of corneal tissue and the viscoelastic properties
      attributed to it. Thus there are two possibilities: either corneal tissue is
      viscoelastic and the experiment showing exponential behaviour suffers from some
      technical problem, or the data is correct and corneal tissue is not viscoelastic.
      In either case further research is necessary for correct interpretation of the
      mechanism of cross-linking and for consequent therapeutic choices.

PMID- 22362228
TI  - A pilot clinical study on the effectiveness of mesoglycan against diabetic
      retinopathy.
AB  - PURPOSE: A double-blind placebo-controlled study on 68 patients suffering by
      Diabetic Retinopathy was aimed in order to evaluate the effectiveness of
      Mesoglycan in this pathology. This drug is particularly interested in treatment
      of disorders of microcirculation. MATERIALS AND METHODS: The two treatments were
      randomly assigned to each patient, using a 100 mg/day dosage of Mesoglycan, and
      both treatments were prescribed for 6 months. The efficacy of both treatments was
      based on clinical and instrumental check. RESULTS: The clinical results that
      emerged in the group treated with Mesoglycan were excellent, although
      observations are on a limited number of patients appears a direct action of
      Mesoglycan on the endothelium retinal blood vessels and circulation. Indeed, in
      the observed patients, was detected a significant reduction of microhemorrhages,
      microaneurysms and exudates. The same cannot be said of the placebo group; none
      of patients of that group showed signs of clinical improvement at the end of the
      study. CONCLUSION: Data emerging from our study show a direct action of
      Mesoglycan on endothelium retinal blood vessels and circulation, as we observed
      in patients we found a significant reduction in the number of microhemorrhages,
      microaneurysms and exudates. This action can be explained by the characteristics
      of drug as antithrombotic profibrinolytic and anti-edema, already found in vitro
      and experimentally. We conclude that our preliminary study showed an encouraging
      clinical efficacy, together with excellent tolerability, and therefore our
      objective has been met, which was to verify the existence of the prerequisites
      for a larger clinical study.

PMID- 22362229
TI  - Ureteric stone in the presence of existing backache: lessons to learn.
AB  - Incidence of urolithiasis is on the rise due to climatic changes especially
      global warming.The pain due to presence of ureteric stone is a well known
      identity but many times it may be asymptomatic or even masked by concurrent
      presence of backache. In the present article, we describe the case of a 43-year
      old male who came to the clinic for treatment of backache persisting for more
      than two years. The patient complained of backache two years back for which he
      was treated with analgesics and physiotherapy which relieved his pain. No X-ray
      was taken earlier because the attending clinician thought the backache to be
      musculo-skeletal in origin. Recently, one day a sudden episode of backache in the
      midst of night compelled him to seek medical treatment. However, this time a X
      ray was performed and it showed the presence of calculi in the right upper pelvis
      of ureter which measured 1.9 cm vertically. An ultrasound confirmed the
      diagnosis. The patient was treated with two episodes of shock wave therapy which
      failed to crush the stone. A Double-J stent was inserted under general
      anaesthesia. The stone was crushed using a ureteroscope guided laser. The present
      case report describes how backache in professionals cannot be lightly attended.
      Even the characteristic groin to loin pain may be absent. All cases of backache
      should be properly investigated with an X-ray to rule out renal or ureteric
      calculi.

PMID- 22362230
TI  - An unique case of thoracic endovascular aortic repair (TEVAR) graft infection
      with Streptococcus viridans.
AB  - The incidence of infection following TEVAR is low. To the best of our knowledge,
      this is the first case report of post thoracic endovascular aortic repair (TEVAR)
      with Streptococcus viridans graft infection. A 54-year-old male underwent TEVAR
      for dissecting thoracic aneurysm with spinal ischaemia. He had an eventful
      recovery with prolonged period of stay in intensive care unit. Three months
      later, he presented with persistent chest discomfort and fever. Computed
      tomography (CT) of the thorax revealed evidence of graft infection and the blood
      culture grew Streptococcus viridans. The rarity of TEVAR graft infection due to
      Streptococcus viridans and its management are being discussed.

PMID- 22362231
TI  - Pisa syndrome secondary to rivastigmine: a case report.
AB  - Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to
      one side giving the appearance of the leaning tower of Pisa. It is most commonly
      caused by typical and atypical antipsychotic drugs. We report a case of Pisa
      Syndrome caused by prolonged use of high dose cholinesterase inhibitor,
      rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not
      reappear when a different cholinesterase inhibitor, donepezil was introduced.
      Physicians should be aware of Pisa syndrome and should alert patient of this
      possibility when starting and stepping up medications. The purpose of reporting
      this case is to create awareness among general practitioners as it is a
      reversible condition which responds to removal of the offending drug.

PMID- 22362233
TI  - [Patient-reported outcomes (PRO): historical profile, definitions,
      classifications and problems].
AB  - This contribution deals with the use, within healthcare systems, of patient
      reported outcomes (PROs), i.e., all measures aimed at quantifying the state of
      health through the evaluation of outcomes reported by the patient himself. A
      survey of their cultural background, identified in the patient-centered model of
      medicine, is followed by a delineation of their historical profile (from 1914,
      the year of the first outcome measure, to the more recent examples of their use
      in clinical trial and practice), a classification based on the size they wish to
      detect and the reconstruction of the main lines of debate around their use in
      health care.

PMID- 22362232
TI  - [Role of rifaximin in the treatment of colonic diverticular disease].
AB  - Diverticular disease of the colon is the fifth most important gastrointestinal
      disease in terms of direct and indirect healthcare costs in western countries.
      Although most patients with colonic diverticula remain asymptomatic for their
      whole life, in 20-25% of cases will develop symptoms. Antibiotics are commonly
      used in the treatment of inflammatory complication of diverticular disease.
      Several clinical observation suggest a role of rifaximin in the management of
      symptomatic uncomplicated diverticular disease of the colon. This is a critical
      review of clinical studies addressing the role of long term administration of
      rifaximin for the treatment of symptomatic colonic diverticular disease. The
      evidence from prospective controlled trials suggests that rifaximin is effective
      for obtaining symptomatic relief in patients with uncomplicated diverticular
      disease. The therapeutic gain compared with fiber supplementation only is
      approximately 30%. No definitive conclusion can be drawn regard a possible role
      of rifaximin for preventing diverticulitis.

PMID- 22362234
TI  - Diagnosis and classification of B-cell non-Hodgkin lymphomas. The role of
      multiparameter flow cytometry.
AB  - Immunophenotyping is a routine method to evaluate B-cell non-Hodgkin lymphomas.
      Flow cytometry plays a complementary role in diagnosis and classification of
      these types of lymphomas, since combination of morphologic, immunophenotypic and
      genotypic features is needed to correctly classifying each disease entity.
      Multiparameter flow cytometry, which is now carried out with routine combinations
      of six to eight monoclonal antibodies, allows identifying even small lymphomatous
      cell populations on the basis of aberrant B-cell marker expression and clonality.
      The immunophenotypic patterns obtained by multiparameter flow cytometry are
      useful to correctly diagnose most of cases of specific subtypes of B-cell non
      Hodgkin lymphomas and to discover peculiar clinical presentations, such as
      discordant and composite lymphomas. Immunophenotypic variability, however,
      characterizes B-cell lymphomas. Therefore, flow cytometry should always be used
      in combination with other techniques to correctly classify each disease entity.
      Finally, multiparameter flow cytometry is characterized by high sensitivity in
      detecting residual disease.

PMID- 22362235
TI  - Iodine-based radiographic contrast medium may precipitate metformin-associated
      lactic acidosis in diabetic patients. A case report, literature review and
      practical approach.
AB  - Lactic acidosis in diabetic patients undergoing metformin therapy is a widely
      recognized, rare but usually serious adverse event, particularly in presence of
      comorbidities such as cardiorespiratory disease, sepsis and renal failure. As
      demonstrated by the case of an elderly woman presented, administration of
      radiographic iodine-based contrast agents may precipitate lactic acidosis through
      worsening of renal function. Awareness of this condition, identification of at
      risk patients, adequate prevention following published guidelines, early
      diagnosis and treatment including hemodialysis are necessary to avoid a fatal
      outcome.

PMID- 22362236
TI  - Information needs of family members of critically ill patients in intensive care
      unit of a tertiary hospital.
AB  - BACKGROUND AND AIMS. The experience in intensive care unit (ICU) has created an
      intense emotional situation both to patients and their family members. The aim of
      this study was to determine the family members information needs of critically
      ill patients in ICU. MATERIALS AND METHODS: A descriptive cross-sectional study
      was conducted on 200 family members of patients admitted in ICU. A face to face
      interview was conducted and a self-report questionnaire of the Critical Care
      Family Needs Inventory (CCFNI) was used. RESULTS: Findings reported CCFNI five
      sub-attributes that ranked from highest to lowest included: support (mean 39.13
      +/- 6.189); proximity (mean 27.17 +/- 3.384); information (mean 24.25 +/- 3.093);
      assurance (mean 22.67 +/- 1.862) and comfort (mean 16.24 +/- 2.776). There were
      no significant differences in needs between family members with different gender
      (p >0.05). However, there were significant differences in support needs between
      family members with admission to ICU with (t=-2.111; p <0.05). There were
      significant differences in assurance needs (F=3.542; p <0.05) and information
      needs (F=3.681; p <0.05) between family members with age. There were no
      significant differences in needs between family members with different education
      level (p >0.05) whereas assurance needs were significant differences with
      education level of (F=3.542; p <0.05). CONCLUSION: The results suggest that
      family members perceived support and proximity as the most crucial need. Comfort
      need was viewed as least important. Although this study was conducted in a
      tertiary hospital, the findings could still provide insight for nurses to improve
      the delivery of care to patients and family members.

PMID- 22362237
TI  - Massive corneal edema treated with corneal cross-linking.
AB  - INTRODUCTION: Massive corneal edema disrupts the fine architecture of corneal
      stroma that guarantees its transparency, causing opacities that seriously impair
      clear vision and are usually solved by corneal transplant. Corneal cross-linking,
      a treatment developed to halt keratoconus progression, results in a loss of water
      and a compaction of corneal stroma. It might therefore be useful to improve the
      pathologic edematous condition of some corneas, ameliorating visual acuity and
      allowing more time for a surgical procedure of keratoplasty. PATIENTS AND
      METHODS: Six patients with visual impairing corneal edemas further to lens
      phacoemulsification, penetrating keratoplasty, or post-infective
      neovascularization were treated with corneal cross-linking alone, or in
      combination with amniotic membrane apposition with or without anti-angiogenic
      therapy. RESULTS: All patients partly resolved the edematous condition, improving
      both corneal transparency and visual acuity. CONCLUSIONS: Corneal cross-linking
      appears to be a useful method to treat massive corneal edemas, so that
      keratoplasty can be at least delayed, and need not to be an emergency treatment
      in these cases.

PMID- 22362238
TI  - [Effects of drinking spa therapy on oxidative stress].
AB  - OBJECTIVES: Data of literature have shown the correlation between oxidative
      stress and some diseases of gastrointestinal and metabolic relevance such as
      diabetes mellitus, gastric cancer, gastritis, etc.. Studies have also shown that
      sulfurous mineral water may be useful in the treatment of gastrointestinal
      diseases. The aim of our research was to evaluate the antioxidant effect of
      sulphurous mineral water, administered by drinking method, in type 2 diabetes
      mellitus, a chronic disease with a high social and economic impact. PATIENTS AND
      METHODS: The study has been performed on 57 subjects (25% women and 75% males;
      mean age: 60 +/- 1.1 years; BMI: 27 +/- 0.4) affected by type 2 Diabetes
      Mellitus. The subjects were divided in four groups: A (subjected to glucose
      lowering diet therapy), B (subjected to antihyperglycaemic therapy), C (exposed
      to glucose-lowering diet therapy + drinking SPA therapy) and D (exposed to
      antihyperglycaemic therapy + drinking SPA therapy). Drinking SPA treatment was
      effected with sulphurous mineral water from Terme of Telese SpA (Benevento -
      Italy) and the pharmacological treatment provided the use of hypoglycemic drugs
      normally used in diabetic disease. After two weeks of therapy with treatments
      considered were evaluated fasting blood glycaemia and plasma concentration of
      ROMs (reactive oxygen metabolites) (d-ROMs test-Diacron International srl(r)
      Grosseto - Italy). RESULTS: The results of our study have shown a significant
      (p<0.05) reduction of the fasting blood glycaemia when to hypoglycemic drugs or
      diet therapy was associated the sulphurous drinking SPA therapy. It was also
      observed a reduction of plasma ROMs levels, significant (p <0.05) in group D
      versus group B. CONCLUSIONS: The data from this preliminary investigation suggest
      that the drinking SPA therapy with sulphurous mineral water, especially in
      combination with antidiabetic drug treatment, may be useful in type 2 diabetes
      mellitus for the improvement redox state of the organism.

PMID- 22362239
TI  - [An unusual cause of chest pain in].
AB  - Myocarditis seems to be mostly caused by a viral infection or more rarely by a
      pharmacological hypersensitivity or by radiations exposure. Nevertheless, it is
      not so easy to know the ethiopathogenesis of the myocarditis, because mostly it
      is impossible to determine the infectious agent that causes the pathology even if
      it is isolated. The diagnosis could often remain uncertain, so a suspect of
      myocarditis has to be opportunely confirmed by specific serological and
      diagnostic investigations, in order to avoid the appearance of a dilated
      cardiomyopathy which is one of its principal sequences.

PMID- 22362240
TI  - [The age factor in bilateral hydrocele diagnosis secondary to a primitive testis
      lymphoma: case report, diagnosis and therapy].
AB  - Primitive NHL represents 9% of testis tumours and the 85% is diagnosed in patient
      older thant 60 years old. Usually pain and a testis mass are the main
      manifestations. The Authors report the case of a 82 years-old man with bilateral
      hydrocele causing severe alteration in the deambulation. The cytology did not
      show blood cells or neoplastic cell in the FNAB. The US showed a complete
      modification in the testis. The patient underwent to surgery intervention of
      vaginalis tunic eversion and resection with the aim of control the symptoms. The
      histology on multiple biopsy of testis and epidydims bilaterally showed a large B
      cell lymphoma. The patient was treated with 6 chemotheray cycles (Rituximab,
      Vincristine, Cyclophosphamide, Prednisone). Bilateral hydrocele is a rare
      clinical presentation of testis NHL. In this patient, blood and neoplastic cell
      absence in the cytology made difficult the differential diagnosis between
      inflammatory pathology and neoplasia. Hystopathologic study and immunologic
      pattern can make a certain diagnosis.

PMID- 22362241
TI  - Cord blood banking: regulations, ethics and practice in a disputed Italian case.
AB  - Current Italian regulations allow the free storage in public biobanks within the
      Italian National Health Service (SSN) of voluntarily donated cord blood, which
      can then be made available for transplantation in Italian and foreign patients.
      The same regulations allow the free storage of cord blood for directed use (in
      other words, for all cases in which it can be used for a family member suffering
      from a disease that can be cured through the use of hematopoietic stem cells) and
      in cases where a family runs a high risk of genetic disorders. This article
      briefly describes and discusses an episode involving an Italian hospital: an
      appeal by a woman led to a court provision imposing the collection and storage of
      a cord blood unit outside the conditions established by law. The provision
      aroused controversy and led to a series of inappropriate actions.

PMID- 22362242
TI  - [Hyponatremic syndrome].
AB  - Sodium, the most important extracellular fluid electrolyte, is the focus of
      several homeostatic mechanisms that regulate fluid and electrolyte balance.
      Hyponatremia is a common electrolyte abnormality caused by an actual sodium
      deficiency or extracellular compartment fluid excess. Clinical symptoms are
      related with acuity and speed with which this abnormality is established. The
      symptoms are mainly neurological and neuromuscular disorders (headache,
      confusion, stupor, seizures, coma) due to brain cells edema. Hyponatremia due to
      sodium deficiency is caused by sodium loss from kidney (nephritis, diuretics,
      mineralocorticoid deficiency) and / or extrarenal (vomiting, diarrhea, burns).
      Hyponatremia due to water excess seems to be the most common and it is
      attributable to cirrhosis, nephrotic syndrome, heart failure, infusion 5% glucose
      solutions and drugs that stimulate ADH secretion. It was recently highlighted the
      role of inflammation and IL-6 in the non-osmotic ADH release. Hyponatremia is
      considered also marker of phlogosis. Acute (<48 h) and severe (<125 mEq/ L)
      hyponatremia is a medical emergency that requires prompt correction. Patients
      with chronic hyponatremia have a high risk of osmotic demyelination syndrome if
      rapid correction of the plasmatic sodium occurs. In combination with conventional
      therapy, a new class of drugs, vasopressin receptors antagonists (AVP-R
      antagonists) would be able to increase the excretion of electrolyte-free water
      and the serum sodium concentration.

PMID- 22362244
TI  - Role of noninvasive ventilation in elderly patients with hypercapnic respiratory
      failure.
AB  - The effectiveness of non-invasive ventilation (NIV) in treating patients with
      acute respiratory failure (ARF) is showed by its ability to diminish the
      recurrence to endotracheal intubation (ETI), the occurrence of ETI-associated
      lung infections as well as related mortality. A specific issue is the outcome of
      NIV in patients referring to Emergency Department for ARF who receive a do-not
      intubate (DNI) order because of too critical conditions or advanced age. Recent
      data show that elderly patients (mean age 81 years) with ARF who have a DNI order
      can be successfully treated by NIV, as demonstrated by a survival rate of 83%.
      The positive outcome was confirmed by a subsequent 3-year observation, that
      demonstrated an overall survival rate of 54%. These findings clearly suggest to
      treat by NIV elderly patients also in presence of a DNI order.

PMID- 22362243
TI  - [Effect of treatment with selective serotonin reuptake inhibitors on lipid
      profile: state of the art].
AB  - Selective Serotonin Reuptake Inhibitors (SSRI) are an effective treatment for
      depressive disorder. Nevertheless, there is evidence suggesting a negative effect
      of these drugs on the lipid profile of the patients. We carried out a systematic
      review of the literature evaluating the influence of therapy with SSRI on lipid
      profile. Data source was MEDLINE. Clinical trials, prospective studies,
      retrospective studies and reviews published until November 2011 were considered.
      We identified twelve studies published from 1994 to 2011, of which four were
      randomized clinical trials, six were prospective studies and two were
      retrospective studies. Sertraline and Paroxetine seemed to have negative effects
      on the serum levels of Total and LDL Cholesterol. Citalopram did not demonstrate
      any influence on Total and LDL Cholesterol blood levels, being conversely
      associated with a slight increase of the HDL Cholesterol levels. Few data were
      found about the effects of Fluoxetina e Fluvoxamina on lipid profile and no data
      were found about Escitalopram. Sertaline and Paroxetine, two effective and widely
      used drugs for the treatment of major depression, seem to have a negative effect
      on the lipid profile; Citalopram, with its neutral or positive effect on lipid
      profile, should be considered the treatment of choice for depressive patients
      affected by dyslipidemia.

PMID- 22362245
TI  - [Psychic disorders in emergency room: a qualitative analysis of psychological
      intervention].
AB  - OBJECTIVES: Our study aims to analyze typologies of psychological intervention
      that respond to spontaneous request of Emergency Room's users and care providers,
      and their distribution in relation to observed psychic disorders. MATERIALS AND
      METHODS: 364 Subjects (134 males and 230 females), mean age 41.55 (+/- 22.38)
      reaching Emergency room were involved in this study. Data from an observation
      form were related to patients' triage code, their provisional diagnosis, the
      request of psychiatric advice and emergency outcome. Non-parametric variables
      were analyzed by Chi Square method, while parametric ones by ANOVA method.
      RESULTS: Patients were the more frequent users of psychological intervention,
      while relatives used it in lesser proportion. Anxiety Disorder was the most
      frequent psychiatric diagnosis associated to psychological consulting. The
      patient's triage code was not significantly related to frequency of consulting.
      The type of intervention that was most often choosen has been supportive. As to
      outcome, the majority of patients who consulted psychologists was discharged,
      while a low percentage was admitted, particularly in psychiatric wards.
      CONCLUSIONS: Psychological consulting appears related to a wider and more varied
      range of urgent situations than psychiatric consulting. Therefore, psychological
      intervention seems to be useful both to relieve hic et nunc psychological
      discomfort, and to help and direct sicker patients to formulate a long-term
      treatment plan.

PMID- 22362246
TI  - Minimally invasive treatment of pancreatic disease.
AB  - Minimally invasive surgery has been widely accepted as an alternative to
      conventional open surgery in many gastrointestinal fields and is now considered
      the standard of care in bariatric surgery as well as oncologic surgery of the
      colon and stomach. Despite the advancements in laparoscopic surgery
      instrumentation and technique, the anatomic relationships of the pancreas and the
      need for complex reconstructions have slowed similar progress in management of
      pancreatic disease. However, numerous recent studies show promising results in
      laparoscopic management of pancreatic pseudocyst, necrosis, and benign and
      malignant pancreatic neoplasms. We present the current status of clinical
      application of minimally invasive techniques for the treatment of complicated
      pancreatitis, chronic pancreatitis, and pancreatic neoplasms, and provide a
      review of the relevant literature. Present day and probable future developments,
      such as the use of robotics, natural orifice techniques, and major vascular
      reconstruction are also presented.

PMID- 22362247
TI  - Doctors in Dickens.

PMID- 22362248
TI  - Seeing through the alcohol statistics haze.

PMID- 22362249
TI  - Exploiting non-communicable disease.

PMID- 22362250
TI  - "One in four" with a mental health problem: the anatomy of a statistic.

PMID- 22362251
TI  - Liposomes self-assembled from electrosprayed composite microparticles.
AB  - Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen
      (NAP) and lecithin (PC), have been successfully prepared using an electrospraying
      process and exploited as templates to manipulate molecular self-assembly for the
      synthesis of liposomes in situ. Field emission scanning electron microscope
      (FESEM) and transmission electron microscope (TEM) observations demonstrate that
      the microparticles have an average diameter of 960 +/- 140 nm and a homogeneous
      structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry
      (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR)
      results verify that the building blocks NAP and PC are scattered in the polymer
      matrix in a molecular way owing to the very fast drying of the electrospraying
      process and the favorable secondary interactions among the components. FESEM,
      scanning probe microscope (SPM) and TEM observations demonstrate that the
      liposomes can be achieved through molecular self-assembly in situ when the
      microparticles contact water thanks to 'like prefers like' and by means of the
      confinement effect of the microparticles. The liposomes have an encapsulation
      rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the
      dissolution medium in a sustained way and by a diffusion mechanism over a period
      of 24 h. The developed strategy not only provides a new, facile, and effective
      method to assemble and organize molecules of multiple components into liposomes
      with electrosprayed microparticles as templates, but also opens a new avenue for
      nanofabrication in a step-by-step and controllable way.

PMID- 22362252
TI  - Paracrine signalling in colorectal liver metastases involving tumor cell-derived
      PDGF-C and hepatic stellate cell-derived PAK-2.
AB  - In a nude mouse model of colorectal liver metastases, we have identified a
      paracrine tumor cell/host cell signalling pathway that is apparently required for
      successful tumor growth. Whereas recombinant platelet derived growth factor-C
      (PDGF-C) and supernatants from PDGF-C secreting wild type LS174T colon carcinoma
      cells could rescue tumor promoting hepatic stellate cells (HSC) from growth
      inhibition by serum starvation, supernatants from LS174T colon carcinoma cells
      with reduced secretion of PDGF-C had much less effect on serum starved HSC.
      Autocrine growth inhibition of LS174T cells by PDGF-C knock-down was only
      marginal. In vivo, a prominent inhibition of liver metastasis was observed if
      PDGF-C was knocked-down in LS174T cells. By whole genome array analysis of host
      cells of the invasion front and subsequent immunohistochemical staining we
      identified p21 activated kinase-2 (PAK-2) as being strongly and specifically
      expressed by HSC. The above described effect of PDGF-C on HSC was found to be
      dependent on PAK-2 because in contrast to wild type HSC, silencing of PAK-2 in
      HSC only allowed for a partial PDGF-C-mediated rescue from serum starvation
      leading to only a slight increase of proliferation. These data indicate that PDGF
      C promotes tumor growth via a growth promoting effect on HSC that is at least in
      part dependent on the presence of functional PAK-2.

PMID- 22362254
TI  - Development of a reverse transcription loop-mediated isothermal amplification
      assay for H7N7 equine influenza virus.
AB  - We have developed a reverse transcription loop-mediated isothermal amplification
      (RT-LAMP) assay for detecting H7N7 equine influenza virus (EIV). The detection
      limit of the RT-LAMP assay was a virus dilution of 10(-4), which was 10 times
      more sensitive than that of Espline Influenza A&B-N and the same as that of
      reverse transcription polymerase chain reaction. The RT-LAMP assay specifically
      amplified H7N7 EIV strains but did not amplify several pathogens related to
      equine respiratory disease including H3N8 EIV strains. Because it provides ease
      of manipulation, the RT-LAMP assay is suitable for large-scale surveillance for
      H7N7 EIV. In addition, the combination of the H3N8 RT-LAMP assay, which was
      developed previously, with the H7N7 RT-LAMP assay should be useful to
      discriminate between H3N8 and H7N7 EIVs in clinical laboratories.

PMID- 22362253
TI  - Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing.
AB  - OBJECTIVE: To prospectively determine the diagnostic accuracy of massively
      parallel sequencing to detect whole chromosome fetal aneuploidy from maternal
      plasma. METHODS: Blood samples were collected in a prospective, blinded study
      from 2,882 women undergoing prenatal diagnostic procedures at 60 U.S. sites. An
      independent biostatistician selected all singleton pregnancies with any abnormal
      karyotype and a balanced number of randomly selected pregnancies with euploid
      karyotypes. Chromosome classifications were made for each sample by massively
      parallel sequencing and compared with fetal karyotype. RESULTS: Within an
      analysis cohort of 532 samples, the following were classified correctly: 89 of 89
      trisomy 21 cases (sensitivity 100%, 95% [confidence interval] CI 95.9-100), 35 of
      36 trisomy 18 cases (sensitivity 97.2%, 95% CI 85.5-99.9), 11 of 14 trisomy 13
      cases (sensitivity 78.6%, 95% CI 49.2-95.3), [corrected] 232 of 233 females
      (sensitivity 99.6%, 95% CI 97.6 to more than 99.9), 184 of 184 males (sensitivity
      100%, 95% CI 98.0-100), and 15 of 16 monosomy X cases (sensitivity 93.8%, 95% CI
      69.8-99.8). There were no false-positive results for autosomal aneuploidies (100%
      specificity, 95% CI more than 98.5 to 100). In addition, fetuses with mosaicism
      for trisomy 21 (3/3), trisomy 18 (1/1), and monosomy X (2/7), three cases of
      translocation trisomy, two cases of other autosomal trisomies (20 and 16), and
      other sex chromosome aneuploidies (XXX, XXY, and XYY) were classified correctly.
      CONCLUSION: This prospective study demonstrates the efficacy of massively
      parallel sequencing of maternal plasma DNA to detect fetal aneuploidy for
      multiple chromosomes across the genome. The high sensitivity and specificity for
      the detection of trisomies 21, 18, 13, and monosomy X suggest that massively
      parallel sequencing can be incorporated into existing aneuploidy screening
      algorithms to reduce unnecessary invasive procedures. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01122524. LEVEL OF
      EVIDENCE: II.

PMID- 22362255
TI  - Reference values of hematological and biochemical parameters for the world
      smallest microminipigs.
AB  - In this study, we demonstrated growth curves and reference values for
      hematological and serum biochemical parameters of Microminipigs, the world
      smallest experimental minipigs. In both male and female animals, the body weights
      (BWs) at 3 and 6 months of age were <5 kg and <10 kg, respectively, and growth
      curve revealed almost plateau (approximately 20 kg BW) after 18 months of age.
      Major hematological and serum biochemical parameters showed no gender differences
      and the values were very similar to those in Gottingen and Yukatan minipigs. The
      values obtained in this study can serve as fundamental reference, and thereby
      facilitate the use of Microminipig in life science research.

PMID- 22362256
TI  - Practical consensus guidelines for the management of enuresis.
AB  - Despite the high prevalence of enuresis, the professional training of doctors in
      the evaluation and management of this condition is often minimal and/or
      inconsistent. Therefore, patient care is neither optimal nor efficient, which can
      have a profound impact on affected children and their families. Once
      comprehensive history taking and evaluation has eliminated daytime symptoms or
      comorbidities, monosymptomatic enuresis can be managed efficaciously in the
      majority of patients. Non-monosymptomatic enuresis is often a more complex
      condition; these patients may benefit from referral to specialty care centers. We
      outline two alternative strategies to determine the most appropriate course of
      care. The first is a basic assessment covering only the essential components of
      diagnostic investigation which can be carried out in one office visit. The second
      strategy includes several additional evaluations including completion of a
      voiding diary, which requires extra time during the initial consultation and two
      office visits before treatment or specialty referral is provided. This should
      yield greater success than first-line treatment. CONCLUSION: This guideline,
      endorsed by major international pediatric urology and nephrology societies, aims
      to equip a general pediatric practice in both primary and secondary care with
      simple yet comprehensive guidelines and practical tools (i.e., checklists, diary
      templates, and quick-reference flowcharts) for complete evaluation and successful
      treatment of enuresis.

PMID- 22362257
TI  - Excess of adiposity in female children and adolescents with juvenile idiopathic
      arthritis.
AB  - This study aims to evaluate the body composition (BC) of female children and
      adolescents with juvenile idiopathic arthritis (JIA). A cross-sectional,
      controlled study was performed to compare the BC between 42 JIA girls and 35
      healthy controls, matched for age and gender. Weight and height were used to
      calculate body mass index (BMI), classified as a Z-score (Z-BMI). BC was
      evaluated by dual-energy X-ray absorptiometry (DXA; DPX-L, Lunar). The fat mass
      index (FMI) was calculated as the ratio between total fat mass and height squared
      (kilograms per square metre). The lean mass index (LMI) was calculated as the
      ratio between total lean mass and height squared (kilograms per square metre). In
      JIA patients, the median of age was 13 years (6-19) and median disease duration
      was 84 months (10.0-215.0). The main disease subtype was polyarticular arthritis
      (54.8%). We observed that 61.9% of patients had normal Z-BMI. JIA girls had
      higher median Z-BMI scores (0.17 vs. -0.48, p = 0.034), total body fat
      percentages (26.5% vs. 16.4%, p = 0.001), truncal fat (4.52 vs. 2.32, p = 0.011)
      and FMI (4.83 vs. 2.23, p < 0.001). For LMI, there was no difference between JIA
      girls and controls (13.45 vs. 12.45, p = 0.212). We did not find association
      between FMI and age, disease subtype, number of limited and/or active joints,
      months since diagnosis and use of corticosteroids or methotrexate. BC changes
      found in JIA girls, such as fatness and adiposity, indicate a potentially greater
      risk for developing hypertension, diabetes mellitus and cardiovascular diseases.
      These findings emphasise the importance of evaluating nutritional status and body
      composition to minimise the emergence of chronic diseases later in life.

PMID- 22362258
TI  - Tc-99m diethylenetriamine pentaacetic acid (DTPA) renal function reserve
      estimation: is it a reliable predictive tool for assessment of preclinical renal
      involvement in scleroderma patients?
AB  - Prognosis of systemic sclerosis (SSc) depends on internal organ involvement. We
      assessed the value of renal function reserve (RFR) for the detection of
      preclinical nephropathy in scleroderma. Thirty SSc patients with normal serum
      creatinine and 30 healthy controls were included. Medsger disease severity score,
      glomerular filtration rate (GFR), and microalbuminuria were measured. Tc-99m DTPA
      was utilized for GFR measurement at baseline and after oral protein overload
      (stimulated GFR). RFR was calculated as the percentile increase of stimulated
      GFR. SSc patients had lower means of baseline GFR (P=0.001), stimulated GFR
      (P=0.004), RFR (P=0.046), and higher microalbuminuria (P=0.009) than controls.
      According to baseline GFR, SSc patients showed three categories-normal baseline
      GFR (n=12), hyperfiltration GFR (n=3), and reduced baseline GFR (n=15). In the
      former category, RFR was normal in 6/12 patients and abnormal in the remainders
      (50%). Hyperfiltration patients and those with reduced baseline GFR showed
      abnormal RFR. A statistically significant negative association was found between
      microalbuminuria versus stimulated GFR and RFR (r= -0.5, P=0.007 and r= -0.45,
      P=0.013, respectively). The majority of SSc patients with abnormal RFR had
      disease duration of >=48 months (60% vs. 20%, P=0.008). All SSc patients with
      pulmonary hypertension had abnormal RFR, while reduced baseline GFR was noted in
      only 60%. A significant negative correlation was found between reduced baseline
      GFR and cumulative dose of corticosteroids in SSc patients (r= -0.4, P=0.022).
      RFR estimation could be a useful predictive marker for preclinical renal
      involvement in SSc patients so that early prophylactic measures and therapy
      modifications could be considered.

PMID- 22362259
TI  - Characteristics of fathers with depressive symptoms.
AB  - Extensive research shows maternal depression to be associated with poorer child
      outcomes, and characteristics of these mothers have been described. Recent
      research describes associations of paternal depressive symptoms and child
      behavioral and emotional outcomes, but characteristics of these fathers have not
      been investigated. This study describes characteristics of fathers with
      depressive symptoms in the USA. Utilizing data from 7,247 fathers and mothers
      living in households with children aged 5-17 years who participated in the
      Medical Expenditure Panel Survey 2004-2006, the Patient Health Questionnaire-2
      was used to assess parental depressive symptoms, the Short Form-12 was used to
      examine paternal and maternal physical health, the Columbia Impairment Scale was
      used to measure child behavioral or emotional problems, and the Children with
      Special Health Care Needs Screener was used to identify children with special
      health care needs. In multivariate analyses, poverty (AOR 1.52; 95% CI 1.05
      2.22), maternal depressive symptoms (AOR 5.77; 95% CI 4.18-7.95), living with a
      child with special health care needs (AOR 1.42, 95% CI 1.04-1.94), poor paternal
      physical health (AOR 3.31; 95% CI 2.50-4.38) and paternal unemployment (AOR 6.49;
      95% CI 4.12-10.22) were independently associated with increased rates of paternal
      depressive symptoms. These are the first data that demonstrate that poverty,
      paternal physical health problems, having a child with special health care needs,
      maternal depressive symptoms, and paternal unemployment are independently
      associated with paternal depressive symptoms, with paternal unemployment
      associated with the highest rates of such problems.

PMID- 22362260
TI  - Sources of potential lead exposure among pregnant women in New Mexico.
AB  - The objectives of this study were to ascertain the prevalence and potential
      sources of lead exposure among pregnant women residing in a socially
      disadvantaged immigrant community in Albuquerque, New Mexico. Pregnant women (n =
      140) receiving prenatal care through a community clinic participated in a
      structured interview and screening to measure their blood lead levels (BLLs).
      Potential sources of lead exposure were ascertained by the CDC and New Mexico
      Department of Health questionnaires. Self-reported risk factors were examined as
      predictors of BLLs using multiple linear regression and partial least squares
      discriminant analysis. Most patients were Spanish-speaking (88.6%), Latina (95%),
      foreign-born (87.1%), lacked health insurance (86.4%), and had a high school
      education or lower (84.3%). While risk factors were prevalent in this population,
      only three women (2.1%) had BLLs >=3 MUg/dL. Results of multivariate analyses
      demonstrated that pica symptoms in pregnancy, history of elevated BLLs before
      pregnancy, use of non-commercial pottery, and living in older houses were
      important predictors of elevated BLLs. Although the prevalence of other risk
      factors relevant to immigrant communities (i.e., use of traditional/folk remedies
      and cosmetics, seasonings and food products from Mexico) was high, they were not
      predictive of elevated BLLs. Clinics providing prenatal care to immigrant
      Hispanic communities should carefully assess patients' pica symptoms, use of non
      commercial pottery, and a history of elevated BLLs. Moreover, additional efforts
      need to focus on the development of screening questionnaires which better reflect
      exposures of concern in this population.

PMID- 22362261
TI  - Provider advice about pregnancy weight gain and adequacy of weight gain.
AB  - To explore the association between health care provider advice about weight gain
      and gestational weight gain. Using data from a prospective cohort study, we
      explored the association between provider advice about weight gain in pregnancy
      with weight gain adequacy among 1,454 pregnant women. Provider advice was
      measured by maternal self-report at 27-30 weeks' gestation. Linear and Poisson
      regression were used to explore associations. Seventy-eight percent of the women
      gained outside current recommendations. Fifty-one percent reported receiving
      weight gain advice from a health care provider. Adjusted Generalized Linear Model
      (GLM) estimates showed weak effect of provider advice on inadequate or excessive
      gain (Relative Risk (RR) 0.96, 95% CI 0.74, 1.26 for inadequate gain and RR 1.01,
      95% CI 0.97, 1.06 for excessive gain). There is a need for more women to hear
      about their targeted weight gains during pregnancy and the present advice that
      exists does little to influence actual gains. Further studies are warranted to
      find better strategies for providers to motivate their patients to gain weight
      within the appropriate ranges.

PMID- 22362262
TI  - Enantioselective synthesis of (-)-paeonilide.
AB  - The first enantioselective synthesis of (-)-paeonilide is reported. Starting from
      inexpensive furan-3-carboxylic acid the targeted monoterpene was obtained in 12
      steps via an asymmetric cyclopropanation-lactonization cascade and a
      stereoselective side chain insertion at an acetal-like position.

PMID- 22362263
TI  - [COPD-specific anxiety and depressive symptoms in COPD patients].
AB  - The aim of the present study was to analyze the associations between COPD
      specific anxiety and depressive symptoms in COPD patients. Anxiety, as well as
      depression, is a prevalent comorbid complication in COPD. Either can have a
      negative impact on patients' experience and the course of disease. So far,
      assessment in studies has exclusively focused on anxiety in general and not on
      disease-related fears. The present study comprised a sample of ninety-six
      patients suffering from COPD (GOLD III/IV). Results of the MANOVA showed higher
      COPD-specific anxiety in patients with depressive symptoms than in patients
      without depressive symptoms. Depressive patients showed a higher fear of social
      isolation, dyspnea related fear, fear of movement and fear of progression of
      disease. There were no differences between the two groups with regard to
      functional parameters (FEV 1 % pred.; 6-minute-walk-test). Overall, our study
      shows the necessity of the assessment of COPD-specific fears related to
      depression to guarantee an adequate treatment.

PMID- 22362264
TI  - The first-principles treatment of the electron-correlation and spin-orbital
      effects in uranium mononitride nuclear fuels.
AB  - The DFT+U calculations were employed in a detailed study of the strong electron
      correlation effects in a promising nuclear fuel-uranium mononitride (UN). A
      simple method for solving the multiple minima problem in DFT+U simulations and
      insure obtaining the correct ground state is suggested and applied. The crucial
      role of spin-orbit interactions in reproduction of the U atom total magnetic
      moment is demonstrated. Basic material properties (the lattice constants, the
      spin- and total magnetic moments on U atoms, the magnetic ordering, and the
      density of states) were calculated varying the Hubbard U-parameter. By varying
      the tetragonal unit cell distortion, the meta-stable states have been carefully
      identified and analyzed. The difference in the magnetic and structural properties
      obtained for the meta-stable and ground states is discussed. The optimal
      effective Hubbard parameter U(eff) = 1.85 eV reproduces correctly the UN anti
      ferromagnetic ordering, and only slightly overestimates the experimental total
      magnetic moment of the U atom and the unit cell volume.

PMID- 22362265
TI  - Estimating vaccination coverage for the trivalent measles-mumps-rubella vaccine
      from trivariate serological data.
AB  - The effectiveness of childhood immunization programs depends on the vaccination
      coverage actually achieved. Routinely collected coverage data are not always
      available, and comparability between countries is often compromised because of
      different data collection methods. In 2000, Gay developed a method to estimate
      trivalent vaccination coverage from readily available trivariate serological data
      on the basis of parametric assumptions related to the rate of seroconversion for
      each vaccine component and probabilities of natural exposure to infection. Gay's
      work was indirectly published in a paper by Altmann and Altmann, who derived
      exact solutions for the parameters on the basis of Gay's modeling equations. In
      this paper, we propose a general likelihood-based marginal model framework to
      extend Gay's model by relaxing two of its main assumptions. We use the Bahadur
      model for trivariate binary data to explicitly account for an association between
      the disease-specific exposure probabilities. We fit several correlation
      structures to measles, mumps, and rubella serology from Belgium and Ireland. For
      both countries, we estimate a small positive pairwise exposure correlation, which
      improves the fit to the data. However, the effect on the estimated vaccination
      coverage and its associated variability is fairly moderate. For both Belgium and
      Ireland, all models reveal that the vaccination coverage achieved during the
      first 15 years since the introduction of measles, mumps, and rubella immunization
      is insufficient to eliminate measles.

PMID- 22362266
TI  - Cardiac dyssynchrony: we have the tools. It is time to use them.

PMID- 22362267
TI  - Does the location of perfusion defects matter? An old question with a new answer.

PMID- 22362268
TI  - Iron(III) catalysed synthesis of unsymmetrical di and trisubstituted ureas--a
      variation of classical Ritter reaction.
AB  - An application of the classical Ritter reaction for the synthesis of
      unsymmetrical di and trisubstituted ureas catalyzed by FeCl(3) is described. The
      protocol is of significant interest in view of the easy availability of
      precursors, mild reaction conditions employed and interestingly its applicability
      for the alkylation of alcohols capable of forming stable carbocationic
      intermediates even to the sterically hindered moieties.

PMID- 22362269
TI  - Current treatment options for metastatic breast cancer: what now?
AB  - Approximately 30% of patients with breast cancer will develop metastatic breast
      disease. Metastatic breast cancer is considered an incurable disease, with
      complete remission rarely achieved after treatment. The goal of treatment for
      metastatic breast cancer patients is to increase overall survival time and delay
      disease progression while ameliorating symptoms and improving or maintaining
      quality of life. Single-agent therapeutic regimens are appropriate for most
      metastatic breast cancer patients. Patients with the luminal A subtype of breast
      cancer, which is more indolent in nature and tends to be more sensitive to
      treatment in general, often respond well to single-agent therapy. Several
      chemotherapy regimens are recommended for the treatment of metastatic breast
      cancer. Compared with single-agent regimens, these combination regimens often
      produce a greater improvement in the rate of objective response as well as a
      prolongation of progression-free survival. There is little evidence, however, of
      improvement in overall survival. Combination chemotherapy regimens are often
      associated with a greater degree of toxicity depending on schedules and doses
      used. The use of bevacizumab in metastatic breast cancer is currently a topic of
      controversy. It is hoped that forthcoming trial data will enable the
      identification of a group of patients, based on tumor biology, who could benefit
      from bevacizumab-based therapy.

PMID- 22362270
TI  - Conjugation of paclitaxel to iron oxide nanoparticles for tumor imaging and
      therapy.
AB  - A strategy for conjugating an antitumor agent to superparamagnetic iron oxide
      nanoparticles (SPIONs) via a biocleavable ester binding is reported. Paclitaxel
      (PTX) was selected as a model drug. Both the in vitro and in vivo performance of
      the conjugates of SPION-PTX was investigated respectively. PTX can be released
      slowly through the hydrolysis of the ester bond in a pH-dependent manner and the
      SPION-PTX has near equal cytotoxity to the clinical PTX injection (Taxol) at the
      equivalent dose of PTX. Furthermore, the SPION-PTX can accumulate in tumor
      tissues as demonstrated by MRI and exhibit better tumor suppression effect than
      Taxol in vivo. The above good performance of the SPION-PTX together with the good
      biocompatibility of the SPIONs would promote greatly the application of the
      SPIONs in the biomedicine field.

PMID- 22362271
TI  - Effective delivery of chemotherapeutic nanoparticles by depleting host Kupffer
      cells.
AB  - Although chemotherapeutic nanoparticles would confer various advantages, the
      majority of administrated nanoparticles are known to be spoiled by the
      reticuloendothelial system (RES). Intending to more effectively deliver
      therapeutic nanoparticles to target regions in vivo, host RES, especially Kupffer
      cells in the liver, have been depleted ahead of drug administration. To
      demonstrate this hypothesis, clodronate liposomes were preinjected into BALB/c
      nude mice for depletion of Kupffer cells 2 days before, and pegylated liposomal
      doxorubicin (Doxil) at the doses of 1.25, 2.5 and 5.0 mg/kg was administered. As
      a result, doxorubicin accumulation in the liver was decreased from 36 to 26%
      injected dose/organ by the Kupffer cells depletion, and consequently, the plasma
      concentration of doxorubicin was significantly enhanced threefold (from 11 to 33
      MUg/mL) on day 1 at 1.25 mg/kg-dose group. Doxorubicin accumulation in the tumor
      was increased from 0.78 to 3.0 MUg/g-tissue on day 3, and tumor growth inhibition
      by Doxil was significantly boosted (tumor volumes from 751 to 482 mm(3)  on day
      24) by the Kupffer cells depletion. In conclusion, Kupffer cells depletion by
      clodronate liposomes enhanced the plasma concentration and antitumor effects of
      Doxil, and would be widely applicable for various clinical cancer chemotherapies
      using nanoparticles.

PMID- 22362272
TI  - A broadly applicable approach to prepare monoclonal anti-cephalosporin antibodies
      for immunochemical residue determination in milk.
AB  - A simple, efficient and rapid method for the synthesis of cephalosporin-protein
      conjugates was established. These conjugates were used as immunogens to produce
      monoclonal antibodies (mAbs) and as solid phase antigens in competitive indirect
      enzyme immunoassays (EIAs). With this generic approach, a novel set of monoclonal
      antibodies for cephalosporins was prepared, including ceftiofur and cephalexin as
      well as, reported here for the first time, cefoperazone, cefquinome and
      cephapirin. All 5 EIAs were highly sensitive, with standard curve IC(50) values
      of 0.7 (ceftiofur), 1.1 (cefquinome), 5.2 (cephalexin), 13.8 (cefoperazone) and
      40.3 ng mL(-1) (cephapirin). Detection limits (IC(30)) ranged from 0.3 (ceftiofur
      mAb 1D7) to 17.2 ng mL(-1) (cephapirin mAb 2F10). Specificity studies revealed
      that cephalosporin-antibody binding was strongly determined by the side chain
      residues of the cephem nucleus. Therefore all mAbs, to some extent, recognized
      other beta-lactam antibiotics with similar side chain residues. Within the group
      of cephalosporins approved for use in veterinary medicine, however, the final
      EIAs were highly selective for their respective antigen, except for the ceftiofur
      EIA which showed cross-reactions with cefquinome. The applicability of the five
      assays for drug residue testing in milk was demonstrated. In each EIA the target
      drug could be determined in milk with high accuracy and precision at
      concentrations far below the European Union maximum residue limits.

PMID- 22362273
TI  - Normalisation of data from allergens proficiency tests.
AB  - The problem of allergen analysis using ELISA kits from different commercial
      products giving significantly different results is widely acknowledged. The
      effect on proficiency testing results is that different assigned values have to
      be generated for the different kits used. Some experimental Food Analysis
      Performance Assessment Scheme (FAPAS) proficiency tests aimed to establish
      whether the use of a standardised calibrant could be used to normalise the
      complete data set without recourse to differentiation. Three recent FAPAS
      proficiency tests (2776 peanut, 2778 soya and 2781 gluten) sent out a second
      spiked sample, in addition to the usual spiked and unspiked samples. Further
      analysis of the data was undertaken after the completion of the tests. The ratio
      of the submitted results for the two spiked samples yielded complete data sets
      which could be tested for normality of the distribution. Where the raw data for
      each individual test sample was clearly non-normal and multi-modal, the ratio
      data yielded a much more normal and symmetrical distribution. The use of one of
      the test samples as a single-point calibrant has some limitations but the
      principle of applying a standardisation clearly works. The development of
      internationally recognised sets of certified reference calibration standards for
      use by allergens testing laboratories would greatly benefit the analysis.

PMID- 22362274
TI  - X-ray photoelectron and scanning Auger electron spectroscopy study of
      electrodeposited ZnCr coatings on steel.
AB  - Zn-Cr alloyed coatings electrochemically deposited are of high interest for
      leading steel manufacturing companies because of their novel properties and high
      corrosion resistance compared with conventional Zn coatings on steel. For tuning
      and optimizing the properties of the electrodeposited Zn-Cr coatings, a broad
      range of the deposition conditions must be studied. For this reason, two
      different types of material were investigated in this study, one with a low
      electrolyte temperature and one with an elevated electrolyte pH, compared with
      the standard values. Because different corrosion performance and delamination
      behaviour of the layers were observed for the two types, advanced surface
      analysis was conducted to understand the origin of this behaviour and to discover
      differences in the formation of the coatings. The topmost surface, the shallow
      subsurface region, and the whole bulk down to the coating-steel interface surface
      were analysed in detail by X-ray photoelectron spectroscopy (XPS) and high
      resolution scanning Auger electron spectroscopy to determine the elemental and
      the chemical composition. For better understanding of the resulting layer
      structure, multiple reference samples and materials were measured and their Auger
      and XPS spectra were fitted to the experimental data. The results showed that one
      coating type is composed of metallic Zn and Cr, with oxide residing only on the
      surface and interface, whereas the other type contains significant amounts of Zn
      and Cr oxides throughout the whole coating thickness.

PMID- 22362276
TI  - Characterization of in vitro metabolic profiles of cinitapride obtained with
      liver microsomes of humans and various mammal species using UHPLC and chemometric
      methods for data analysis.
AB  - An ultra-high performance liquid chromatographic method has been utilized to
      obtain metabolic profiles of cinitapride with liver microsomes of humans and
      various mammal species such as rats, mice, mini pigs, dogs, and monkeys.
      Metabolites have been generated by incubation of cinitapride in the presence of
      microsomes using nicotinamide adenine dinucleotide phosphate as a cofactor.
      Incubation times from 15 to 60 min have been assayed. Cinitapride and its
      metabolites have been separated by reversed-phase C(18) mode using ammonium
      formate aqueous solution (pH 6.5) and acetonitrile as the components of the
      mobile phase. Concentrations of metabolites in the incubated samples have
      resulted in an excellent source of multivariate data to be used to extract
      metabolic information. Statistic parameters and principal component analysis have
      been used to compare the in vitro metabolism of humans with the other species.

PMID- 22362275
TI  - Automated annotation and quantification of metabolites in 1H NMR data of
      biological origin.
AB  - In (1)H NMR metabolomic datasets, there are often over a thousand peaks per
      spectrum, many of which change position drastically between samples. Automatic
      alignment, annotation, and quantification of all the metabolites of interest in
      such datasets have not been feasible. In this work we propose a fully automated
      annotation and quantification procedure which requires annotation of metabolites
      only in a single spectrum. The reference database built from that single spectrum
      can be used for any number of (1)H NMR datasets with a similar matrix. The
      procedure is based on the generalized fuzzy Hough transform (GFHT) for alignment
      and on Principal-components analysis (PCA) for peak selection and quantification.
      We show that we can establish quantities of 21 metabolites in several (1)H NMR
      datasets and that the procedure is extendable to include any number of
      metabolites that can be identified in a single spectrum. The procedure speeds up
      the quantification of previously known metabolites and also returns a table
      containing the intensities and locations of all the peaks that were found and
      aligned but not assigned to a known metabolite. This enables both biopattern
      analysis of known metabolites and data mining for new potential biomarkers among
      the unknowns.

PMID- 22362277
TI  - Characterisation of diamond coatings with different morphologies by Raman
      spectroscopy using various laser wavelengths.
AB  - Since the beginning of low-pressure diamond synthesis, Raman spectroscopy has
      been widely used to identify and characterise the quality of diamonds. The
      diamond crystal is characterised by a Raman peak at about 1,332 cm(-1). Other
      peaks are associated with miscellaneous carbon structures, e.g. graphite and
      amorphous phases. In recent years, both well-faceted crystalline diamonds and
      nanocrystalline and ultrananocrystalline diamonds have been investigated. For
      these fine-grained materials, the diamond peak at 1,332 cm(-1) disappears and the
      intensities of peaks at other wavelengths increase. To study the influence of the
      Raman laser wavelength, three lasers were used (472.681 nm, blue; 532.1 nm,
      green; 632.81 nm, red). For well-faceted diamonds, the Raman spectra with blue
      and green laser light were similar. A shift of the peak maxima and different
      intensities were observed. With use of the red laser, a strong luminescence peak
      and low peak intensities for the various carbon-related peaks occurred. When the
      diamond morphology changes from well-faceted to fine-grained ballas diamond, the
      spectra are similar for all three lasers.

PMID- 22362278
TI  - Electrosynthesis of polypyrrole on steel fiber for solid-phase microextraction of
      citalopram in serum.
AB  - A solid-phase microextraction (SPME) technique using steel fiber coated with
      polypyrrole (PPY) was developed for UV-Vis determination of citalopram in blood
      serum. The coating was prepared using a three-electrode electrochemical system
      from an acetonitrile/aqueous (ACN/H(2)O) oxalic acid solution containing 0.01 M
      of pyrrole monomer by applying a potential range (0-1.3 V) for 25 min. In order
      to obtain an efficient film of PPY, experimental parameters related to the
      coating process were optimized, specifically deposition potential, concentration
      of monomer, and number of cycles. The effects of various parameters on the
      efficiency of the SPME process such as extraction time, stirring speed,
      adsorption and desorption temperature, desorption solvent, and pH of desorption
      solution were also studied. The coating was stable and adhered to the surface of
      the steel fiber. The method was linear over about three orders of magnitude with
      an average correlation coefficient of 0.97. Spiking of blank samples with 0.2
      MUg/mL citalopram afforded a recovery of 84% with a precision of 10.2%. A limit
      of detection of 0.046 MUg/mL (based on S/N = 3) was obtained in the linear
      dynamic range of 0.046-2.0 MUg/mL. The proposed method was applied to monitor
      citalopram in serum samples.

PMID- 22362279
TI  - Current use of high-resolution mass spectrometry in the environmental sciences.
AB  - During the last two decades, mass spectrometry (MS) has been increasingly used in
      the environmental sciences with the objective of investigating the presence of
      organic pollutants. MS has been widely coupled with chromatographic techniques,
      both gas chromatography (GC) and liquid chromatography (LC), because of their
      complementary nature when facing a broad range of organic pollutants of different
      polarity and volatility. A clear trend has been observed, from the very popular
      GC-MS with a single quadrupole mass analyser, to tandem mass spectrometry (MS-MS)
      and, more recently, high-resolution mass spectrometry (HRMS). For years GC has
      been coupled to HR magnetic sector instruments, mostly for dioxin analysis,
      although in the last ten years there has been growing interest in HRMS with time
      of-flight (TOF) and Orbitrap mass analyzers, especially in LC-MS analysis. The
      increasing interest in the use of HRMS in the environmental sciences is because
      of its suitability for both targeted and untargeted analysis, owing to its
      sensitivity in full-scan acquisition mode and high mass accuracy. With the same
      instrument one can perform a variety of tasks: pre- and post-target analysis,
      retrospective analysis, discovery of metabolite and transformation products, and
      non-target analysis. All these functions are relevant to the environmental
      sciences, in which the analyst encounters thousands of different organic
      contaminants. Thus, wide-scope screening of environmental samples is one of the
      main applications of HRMS. This paper is a critical review of current use of HRMS
      in the environmental sciences. Needless to say, it is not the intention of the
      authors to summarise all contributions of HRMS in this field, as in classic
      descriptive reviews, but to give an overview of the main characteristics of HRMS,
      its strong potential in environmental mass spectrometry and the trends observed
      over the last few years. Most of the literature has been acquired since 2005,
      coinciding with the growth and popularity of HRMS in this field, with a few
      exceptions that deserve to be mentioned because of their relevance.

PMID- 22362280
TI  - Evaluating a direct swabbing method for screening pesticides on fruit and
      vegetable surfaces using Direct Analysis in Real Time (DART) coupled to an
      Exactive benchtop orbitrap mass spectrometer.
AB  - Rapid screening of pesticides present on the surfaces of fruits and vegetables
      has been facilitated by using a Direct Analysis in Real Time (DART((r))) open air
      surface desorption ionization source coupled to an Exactive((r)) high-resolution
      accurate mass benchtop orbitrap mass spectrometer. The use of cotton and
      polyester cleaning swabs to collect and retain pesticides for subsequent open air
      desorption ionization is demonstrated by sampling the surface of various produce
      to which solutions of pesticides have been applied at levels 10 and 100 times
      below the tolerance levels established by the United States Environmental
      Protection Agency (US EPA). Samples analyzed include cherry tomatoes, oranges,
      peaches and carrots each chosen for their surface characteristics which include:
      smooth, pitted, fuzzy, and rough respectively. Results from the direct analysis
      of fungicides on store-bought oranges are also described. In all cases, the swabs
      were introduced directly into the heated ionizing gas of the DART source
      resulting in production of protonated pesticide molecules within seconds of
      sampling. Operation of the orbitrap mass spectrometer at 25,000 full-width half
      maximum resolution was sufficient to generate high-quality accurate mass data.
      Stable external mass calibration eliminated the need for addition of standards
      typically required for mass calibration, thus allowing multiple analyses to be
      completed without instrument recalibration.

PMID- 22362281
TI  - Size engineering of metal nanoparticles to diameter-specified growth of single
      walled carbon nanotubes with horizontal alignment on quartz.
AB  - The electronic, physical and optical properties of single-walled carbon nanotubes
      (SWNTs) are governed by their diameter and chirality, and thus much research has
      been focused on controlling the diameter and chirality of SWNTs. To date, control
      of the catalyst particle size has been thought to be one of the most promising
      approaches to control the diameter or chirality of SWNTs owing to the correlation
      between catalyst particle size and tube diameter.In this study, we demonstrate
      the size engineering of catalytic nanoparticles for the controlled growth of
      diameter-specified and horizontally aligned SWNTs on quartz substrates. Uniformly
      sized iron nanoparticles derived from ferritin molecules were used as a catalyst,
      and their size was intentionally decreased via thermal heat treatment at 900 
      degrees C under atmospheric Ar ambient. ST-cut quartz wafers were used as growth
      substrates in order to elucidate the effect of the size of the nanoparticles on
      the tube diameter and the effect of catalyst size on the degree of parallel
      alignment on the quartz substrates. SWNTs grown by chemical vapor deposition
      using methane as feedstock exhibited a high degree of horizontal alignment when
      the particle density was low enough to produce individual SWNTs without bundling.
      Annealing for 60 min at 900  degrees C produced a reduction of nanoparticle
      diameter from 2.6 to 1.8 nm and a decrease in the mean tube diameter from 1.2 to
      0.8 nm, respectively. Raman spectroscopy results corroborated the observation
      that prolonged heat treatment of nanoparticles yields thinner tubes with narrower
      size distributions. The results of this work suggest that straightforward thermal
      annealing can be a facile way to obtain uniform-sized SWNTs as well as catalytic
      nanoparticles.

PMID- 22362282
TI  - Solving inverse problems for biological models using the collage method for
      differential equations.
AB  - In the first part of this paper we show how inverse problems for differential
      equations can be solved using the so-called collage method. Inverse problems can
      be solved by minimizing the collage distance in an appropriate metric space. We
      then provide several numerical examples in mathematical biology. We consider
      applications of this approach to the following areas: population dynamics, mRNA
      and protein concentration, bacteria and amoeba cells interaction, tumor growth.

PMID- 22362283
TI  - Subarachnoid hemorrhage complicated with neurogenic pulmonary edema and takotsubo
      like cardiomyopathy.
AB  - Patients with poor-grade subarachnoid hemorrhage (SAH) are often complicated with
      acute cardiopulmonary dysfunctions, particularly neurogenic pulmonary edema (NPE)
      and takotsubo-like cardiomyopathy (TCM). This study retrospectively investigated
      the incidence, demographics, clinical characteristics, and outcomes of patients
      with SAH complicated with both NPE and TCM (NPE-TCM). The effects of aneurysm
      location and other clinical variables on the incidence of NPE-TCM were also
      investigated. Among 234 SAH patients treated during 5-year period, 16 (7%)
      presented with NPE, and transthoracic ultrasonography revealed that 14 of these
      16 patients (88%) also had TCM. All 14 patients with NPE-TCM had poor-grade SAH
      (World Federation of Neurosurgical Societies grades IV and V). Ruptured posterior
      circulation aneurysm was predictive of NPE-TCM, but other clinical variables were
      not. Eight of the 14 patients with NPE-TCM could undergo treatment for ruptured
      aneurysm. Long-term outcomes were favorable in 5 of the 8 patients. Grade IV SAH
      patients had significantly better outcomes than grade V patients. TCM develops
      frequently in SAH patients presenting with NPE, and transthoracic ultrasonography
      should be conducted routinely in that population. Patients with ruptured
      posterior circulation aneurysm may have elevated risk of developing NPE-TCM.
      Endovascular obliteration of the aneurysm may be preferable to open surgery, but
      the optimal treatment modality needs to be evaluated further. Considering the
      limited number of SAH patients complicated with NPE-TCM, a multi-center
      cooperative study may be required.

PMID- 22362284
TI  - Direct surgical treatment of giant middle cerebral artery aneurysms using
      microvascular reconstruction techniques.
AB  - Giant intracranial aneurysm is a life-threatening lesion and treatment of the
      aneurysm could be hazardous and complex. This study describes direct surgical
      treatment of giant middle cerebral artery (MCA) aneurysms using microvascular
      reconstruction techniques in 13 patients treated between 2006 and 2009. In all 13
      patients, superficial temporal artery (STA)-MCA (M(2)) anastomosis was performed
      as a precaution prior to attacking the aneurysm. During surgery, microvascular
      reconstruction of incorporative arteries was additionally performed if the
      aneurysm was removed. Direct neck clipping was performed in four patients,
      trapping and removal of the aneurysm in one, and removal of the aneurysm with
      vascular reconstruction of the MCA in eight patients. Minor ischemic
      complications due to perforator ischemia were recognized in 6 patients, and 10
      patients achieved functionally favorable outcomes (modified Rankin scale score 0
      or 1). In direct surgery for giant MCA aneurysm, precautionary STA-M(2) bypass
      could provide appropriate surgical strategies tailored to individual cases,
      including direct clipping and removal of the aneurysm with or without vascular
      reconstruction. Microvascular reconstruction techniques are essential for
      complete cure of giant MCA aneurysms.

PMID- 22362285
TI  - Molecular targeting therapy against promyelocytic leukemia protein using arsenic
      acids in experimental intracranial medulloblastoma.
AB  - Our previous study using human Daoy medulloblastoma cells showed that the
      promyelocytic leukemia (PML) gene was significantly upregulated (2.5-fold) in
      cells positive to prominin-1 antigen (CD133), a possible marker for cancer
      initiating cells. Arsenic trioxide (As(2)O(3)) is known to degrade PML protein
      and has been used for the treatment of patients with acute PML. In the present
      study, the effect of PML targeting therapy with As(2)O(3) and cytarabine (Ara-C)
      on Daoy medulloblastoma cell proliferation was investigated. Daoy cells were
      pretreated with As(2)O(3) for 6 weeks. The As(2)O(3)-pretreated Daoy cells were
      cultured in medium containing Ara-C and cell viability was examined. Next, the
      As(2)O(3)-pretreated Daoy cells were inoculated into the nude mouse brain and the
      effect of Ara-C on the tumor size was evaluated. A significant increase in
      chemosensitivity to Ara-C was observed in the As(2)O(3)-pretreated Daoy cells in
      both in vitro and in vivo conditions. PML and CCND1 (cyclin D1) protein
      expression of Daoy medulloblastoma cells was downregulated by As(2)O(3)
      treatment. PML has been proposed as a novel therapeutic target to eradicate
      quiescent leukemia-initiating cells, and PML-expressing CD133-positive cells are
      similarly a potential therapeutic target of treatment for medulloblastoma.

PMID- 22362286
TI  - Diffusion tensor imaging of idiopathic normal pressure hydrocephalus: a voxel
      based fractional anisotropy study.
AB  - Diffusion tensor imaging (DTI) using a 3.0 tesla magnetic resonance scanner was
      used to investigate white matter changes caused by idiopathic normal pressure
      hydrocephalus (INPH) in 10 patients diagnosed by clinical symptoms (gait
      disturbance, dementia, and/or urinary incontinence) and Evans index >0.3, and
      compared with findings for 10 age-matched controls (>=60 years). Then, using a
      computer-automated method, fractional anisotropy (FA) brain maps were generated
      and finally transformed into the standard space. Voxel-based FA values within two
      regions of interests (ROIs), the forceps minor and corticospinal tracts, were
      then separately evaluated. Within each ROI, statistical comparisons of results
      from the INPH and control groups were performed. In addition, for INPH patients,
      grading scores for clinical symptoms and FA values were correlated. The forceps
      minor mean FA value was much smaller for the INPH group (0.504) than for the
      control group (0.631). The corticospinal tract mean FA value was slightly smaller
      for the INPH group (0.588) than for the control group (0.632). Additional
      analyses indicated that lower FA values within the forceps minor tended to be
      associated with clinical symptoms such as urinary incontinence and gait
      disturbance. Our findings indicate FA values decreased in the forceps minor of
      INPH patients. We also found that lower values were associated with severer
      clinical symptoms, implying that DTI techniques may be developed for more
      accurate diagnosis.

PMID- 22362287
TI  - Cervical neuro-muscular syndrome: discovery of a new disease group caused by
      abnormalities in the cervical muscles.
AB  - Our previous study of whiplash injury found that abnormalities in the cervical
      muscles cause autonomic dystonia. Further research has found that abnormalities
      in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and
      dizziness. We named this group of diseases cervical neuro-muscular syndrome.
      Patients treated within a 2-year period from April 1, 2002 to March 31, 2004
      reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness,
      84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for
      whiplash-associated disorder. A large number of outpatients present with general
      malaise, including many general physical complaints without identifiable cause.
      We propose that treatment of the cervical muscle is effective for general
      malaise.

PMID- 22362288
TI  - Ruptured aneurysm of a posterior inferior cerebellar artery communicating artery.
      Case report and histological findings.
AB  - A hypertensive 60-year-old man presented with a rare aneurysm arising from the
      posterior inferior cerebellar artery (PICA) communicating artery, manifesting as
      subarachnoid hemorrhage with intraventricular hemorrhage. Angiography showed a
      small aneurysm arising from a fine and tortuous artery interconnecting the
      bilateral vermian branches of distal PICAs. The right PICA was absent and its
      vermian territory was supplied by the left PICA through this communicating
      artery. The right anterior inferior cerebellar artery was also connected to the
      vermian branch of the right PICA. At surgery, a reddish and apparent fusiform
      aneurysm was noted at the top of the arterial loop under the cerebellar vermis.
      Microsurgical trapping and removal of the aneurysm was performed without
      complication. Histological examination demonstrated typical findings of a true
      aneurysm. Only four previous cases of aneurysm of the communicating artery
      between the bilateral distal PICAs have been reported. In all five reported cases
      including ours, the PICA communicating artery contributed to the collateral blood
      supply of the contralateral vermian territory based on vascular anomalies.
      Hemodynamic stress and congenital vulnerability may have caused this aneurysm.
      Trapping is suitable to treat this precarious aneurysm if other collateral
      vessels supply the contralateral vermian territory.

PMID- 22362289
TI  - Clip blade scissoring with titanium bayonet clip in aneurysm surgery. Two case
      reports.
AB  - Scissoring of the cerebral aneurysm clip blades is a rare but potentially
      devastating complication of clipping surgery and results in aneurysm neck injury
      inducing rupture and/or cerebral infarction. Scissoring has been reported using
      titanium straight clips. Here we present two unusual cases of crossing of the
      blades of titanium bayonet clips by a scissors-like mechanism during surgery. The
      present cases suggest the following points. Bayonet clips in addition to straight
      clips may display the scissoring phenomenon during clipping surgery. The slipped
      clip should be removed immediately because the scissor-like deformed aneurysm
      clip may slip further and result in parent artery stenosis. Scissoring tends to
      happen in the presence of partial arteriosclerosis of the aneurysm neck. Before a
      titanium clip is used to treat an aneurysm with partially arteriosclerotic neck,
      reducing the amount of aneurysm filling by temporary clipping of the main vessel
      is useful to avoid slippage phenomena.

PMID- 22362290
TI  - Acute occlusion and recanalization of vertebral artery dissection after
      subarachnoid hemorrhage: usefulness of bilateral simultaneous vertebral
      angiography and basiparallel anatomic scanning-magnetic resonance imaging. Case
      report.
AB  - A 41-year-old man presented with subarachnoid hemorrhage. Initial digital
      subtraction angiography showed occlusion of the right vertebral artery (VA),
      which recanalized immediately, and dissecting aneurysm on the distal part of the
      right VA. Basiparallel anatomic scanning (BPAS)-magnetic resonance (MR) imaging
      showed the morphology of the aneurysm clearly. Coil embolization of the entire
      affected artery was performed using bilateral vertebral angiography road mapping.
      Although acute occlusion of ruptured VA dissection may have the potential for
      natural healing, spontaneous recanalization seems to be hazardous because of
      rebleeding. In cases with acute occlusion of parent artery, BPAS-MR imaging and
      bilateral simultaneous vertebral angiography may give useful information.

PMID- 22362291
TI  - Supra-diaphragmatic pituitary adenoma removed through the trans-tuberculum sellae
      approach. Case report.
AB  - A 59-year-old woman presented with a rare supra-diaphragmatic pituitary adenoma
      manifesting as a mass lesion. Her baseline data and the response of anterior
      pituitary hormones to the provocation test were within the normal range. Magnetic
      resonance imaging showed a homogeneously enhanced tumor located on the diaphragma
      sellae. The tumor was totally removed by the endonasal trans-tuberculum sellae
      approach under combined microscopic and endoscopic observation. Her postoperative
      course was uneventful and the histological diagnosis was pituitary adenoma
      located in the suprasellar region. The trans-tuberculum sellae approach is a less
      invasive method to remove pituitary adenoma located in the suprasellar region.

PMID- 22362292
TI  - Ganglioneuroma originating from the trigeminal nerve in the middle cranial fossa.
      Case report.
AB  - A 55-year-old man present with a case of ganglioneuroma manifesting as sudden
      onset of severe headache. T(1)-weighted magnetic resonance imaging demonstrated a
      heterogeneously enhanced mass (3 * 3 * 2.5 cm) in the left middle cranial fossa
      compressing the left cavernous sinus. The tumor was totally removed through a
      frontozygomatic approach. The histological diagnosis was ganglioneuroma
      originating from the second division of the trigeminal nerve in the middle
      cranial fossa. Ganglioneuroma can occur wherever ganglion cells exist, but
      ganglioneuroma originating from the trigeminal nerve is rare, with only two cases
      reported.

PMID- 22362293
TI  - Glioblastoma associated with intratumoral abscess formation. Case report.
AB  - A 45-year-old man presented with a rare case of glioblastoma associated with
      intratumoral abscess formation manifesting as headache and vomiting after an
      appendectomy. Computed tomography and magnetic resonance imaging demonstrated a
      ring-enhanced lesion mimicking malignant glioma. Craniotomy and tumor removal
      were performed. Abscess formation within the intra-axial tumor was found
      intraoperatively. Histological examination revealed glioblastoma with abscess,
      and the etiological agent was anaerobic Gram-negative bacilli. The suspected
      route of microbial migration and colonization in this tumor was bacteremia from
      appendicitis.

PMID- 22362294
TI  - Spontaneous thrombosis of a spinal conus perimedullary arteriovenous fistula.
      Case report.
AB  - A 49-year-old male presented with a rare case of acute lower extremity paresis
      caused by spontaneous thrombosis of a spinal conus perimedullary arteriovenous
      fistula (AVF) after a subacute myelopathic course. Magnetic resonance imaging
      obtained after deterioration showed that the flow voids around the conus
      medullaris had changed from hypointense to hyperintense lesions. Surgery with
      thoracic laminoplasty was performed to determine the nature of the lesion because
      angiography was negative. During surgery, thrombosed abnormal vessels were
      observed, consistent with thrombosis of a spinal conus perimedullary AVF.
      Histological specimens of the thrombosed vessels exhibited vascular wall injury
      such as intimal alteration, wall dissection, and mural thrombus. Hemorrhage and
      infection were excluded. Vascular wall injury of draining veins and varices were
      probably one of the causes of thrombosis in the present case. Spinal
      arteriovenous malformation generally causes progressive venous congestive
      myelopathy, but the congestive myelopathy may rarely rapidly deteriorate with
      spontaneous thrombosis, known as Foix and Alajouanine syndrome.

PMID- 22362295
TI  - Symptomatic gas-containing herniated disc with the vacuum phenomenon: mechanism
      and treatment. Case report.
AB  - A 76-year-old woman presented with an extremely rare case of symptomatic gas
      containing disc herniation manifesting as left posterolateral thigh pain and
      ankle dorsiflexion motor weakness. The diagnosis was L3-4 vacuum disc associated
      with epidural pneumorrhachis. The patient underwent partial hemilaminectomy and
      cyst incision. After incising the cyst, the thecal sac and root were decompressed
      sufficiently. Vacuum disc is a common phenomenon in the elderly rarely associated
      with pneumorrhachis and is usually asymptomatic. Symptomatic epidural gas
      containing herniated discs with the vacuum phenomenon are very rare. Gas
      aspiration should be considered, but excision of the gas-containing herniated
      disc should be performed in patients with neurological deficits, frequent
      recurrence, or difficult location to approach.

PMID- 22362296
TI  - Cerebral and subdural abscess with spatio-temporal multiplicity 12 years after
      initial craniotomy for acute subdural hematoma. Case report.
AB  - A 34-year-old man presented with a case of subdural empyema and cerebral abscess
      that developed 12 years after initial neurosurgical intervention for a traffic
      accident in 1998. Under a diagnosis of acute subdural hematoma and cerebral
      contusion, several neurosurgical procedures were performed at another hospital,
      including hematoma removal by craniotomy, external decompression, duraplasty, and
      cranioplasty. The patient experienced an epileptic seizure, and was referred to
      our hospital in March 2010. Magnetic resonance imaging revealed a cerebral
      abscess extending to the subdural space just under the previous surgical field.
      Surgical intervention was refused and antimicrobial treatment was initiated, but
      proved ineffective. Surgical removal of artificial dura and cranium with subdural
      empyema, and resection of a cerebral abscess were performed on May 12, 2010. No
      organism was recovered from the surgical samples. Meropenem and vancomycin were
      selected as perioperative antimicrobial agents. No recurrence of infection has
      been observed. Postneurosurgical subdural empyema and cerebral abscess are
      recently emerging problems. Infections of neurosurgical sites containing
      implanted materials occur in 6% of cases, usually within several months of the
      surgery. Subdural empyema and cerebral abscess developing 12 years after
      neurosurgical interventions are extremely rare. The long-term clinical course
      suggests less pathogenic organisms as a cause of infection, and further
      investigations to develop appropriate antimicrobial selection and adequate
      duration of antimicrobial administration for these cases are needed.

PMID- 22362297
TI  - Chronic subdural hematoma associated with arachnoid cyst. Two case histories with
      pathological observations.
AB  - Arachnoid cysts are well known to induce chronic subdural hematoma (CSDH) after
      head injury. However, histological observations of the arachnoid cyst and
      hematoma membrane have only been rarely described. An 8-year-old boy and a 3-year
      old boy presented with CSDH associated with arachnoid cyst. Surgical removal of
      the hematoma and biopsy of the hematoma membrane and cyst wall were performed.
      Clinical courses were good and without recurrence more than 1.5 years after
      surgery. Histological examination suggested that the cysts did not contribute to
      hematoma development. Pediatric hematoma membranes, similar to adult hematoma
      membranes, are key in the growth of CSDH. Therefore, simple hematoma evacuation
      is adequate as a first operation for CSDH associated with arachnoid cyst.

PMID- 22362298
TI  - Declining in-hospital mortality in patients undergoing coronary bypass surgery in
      the United States irrespective of presence of type 2 diabetes or congestive heart
      failure.
AB  - BACKGROUND: Significant advances in surgical techniques and postsurgical care
      have been made in the last 10 years. The goal of this study was to evaluate any
      decline in the age-adjusted in-hospital mortality rate of patients undergoing
      coronary artery bypass grafting (CABG) using a national database from 1989 to
      2004 in the United States. HYPOTHESIS: Reduction in CABG related mortality in
      recent years. METHODS: Using the Nationwide Inpatient Sample (NIS) database, we
      obtained specific ICD-9-CM codes forCABG to compile the data. To exclude
      nonatherosclerotic cause of coronary disease, we studied only patients older than
      40 years. We calculated total and age-adjusted mortality rate per 100,000 for
      this period. RESULTS: The NIS database contained 1 145 285 patients who had CABG
      performed from 1988 to 2004. The mean age for these patients was 71.05 +/- 9.20
      years. From 1989, the age-adjusted rate for all CABG-related mortality has been
      decreasing steadily and reached the lowest level in 2004: 300.3 per 100 000 in
      1989, (95%confidence interval [CI], 20.4-575.9) and 104.69 per 100 000 (95% CI,
      22.6-186.7) in 2004. Total death also declined from 5.5% to 3.06%. This decline
      occurred irrespective of comorbidities such as congestive heart failure,
      diabetes, or acute myocardial infarction, albeit increasing the number of CABG
      procedures performed in high-risk patients. CONCLUSIONS: The age-adjusted in
      hospital mortality rate from CABG has been declining steadily and reached its
      lowest level in 2004, irrespective of comorbidities. This decline most likely
      reflects advances in surgical techniques and the use of evidence-based medicine
      in patients undergoing CABG.

PMID- 22362299
TI  - Protease inhibitor monotherapy: what is its role?
AB  - Protease inhibitor monotherapy has been shown to be effective in maintaining long
      term viral suppression in a majority of patients. Withdrawal of nucleoside
      analogues can prevent long-term toxicity related to these drugs. Clinical trials
      have recently reported preliminary data on the beneficial effect of protease
      inhibitor monotherapy on body fat distribution and bone metabolism. Some of the
      uncertainties possibly associated with protease inhibitor monotherapy such as the
      increased risk of neurological events and a higher level of subclinical
      inflammation will be discussed in this review.

PMID- 22362300
TI  - BRG1 expression is increased in human glioma and controls glioma cell
      proliferation, migration and invasion in vitro.
AB  - PURPOSE: The purposes of our study were to elucidate the role of BRG1 in the
      development of human glioma and to determine the effect of BRG1 on glioma cell
      growth, migration and invasion. METHODS: Using tissue microarray and
      immunohistochemistry, we evaluated BRG1 staining in 190 glioma tissues, 8 normal
      brain tissues and 8 tumor adjacent normal brain tissues. We studied glioma cell
      proliferative ability with reduced BRG1 expression by siRNA using CCK-8 cell
      proliferation assay and cell cycle analysis. We studied the role of BRG1 in
      glioma cell migration and invasion by cell migration assay and matrigel invasion
      assay. We performed western blot to detect cyclin D1, cyclin B1 and MMP-2 protein
      expression. We also detected MMP-2 enzyme activity by gelatin zymography.
      RESULTS: Our results showed that BRG1 expression was increased in benign tumor
      and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01
      for both). We did not find any correlation between BRG1 expression and
      clinicopathological parameters. In addition, we found that knockdown of BRG1 in
      glioma cell lines inhibits cell growth due to the G1 phase arrest by
      downregulating cyclin D1. We further demonstrated that silencing of BRG1 in
      glioma cells inhibited the cell migration and invasion abilities, and
      downregulation of MMP-2 expression greatly contributed to the reduced cell
      invasion and migration abilities. CONCLUSIONS: Our data indicated that BRG1
      expression is significantly increased in human glioma and it may be involved in
      the process of glioma cell proliferation, migration and invasion.

PMID- 22362301
TI  - Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions
      in patients with early and metastatic breast cancer.
AB  - PURPOSE: Breast cancer (BC) is a complex, multi-stage disease involving
      deregulation of different signaling cascades. The present study was conducted to
      determine the extent of apoptosis, angiogenesis, inflammation, and oxidative
      stress in patients with different stages of BC as an approach to disease
      biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as
      antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-alpha as
      apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide
      (NO) as oxidative stress and angiogenic indices were measured in patients with
      BC. METHODS: Thirty-seven newly diagnosed patients with BC, 30 patients with
      benign breast masses, and 30 healthy controls were recruited. Plasma levels of
      sFas, bcl-2, IL-8, and TNF-alpha were measured by immunosorbent assay kits and
      LPO and NO by chemical methods. RESULTS: Plasma sFas and LPO were significantly
      higher in BC patients versus benign breast masses and healthy controls (P <
      0.0001). Bcl-2, IL-8, TNF-alpha, and NO were significantly higher in benign
      breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001)
      versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2,
      IL-8, TNF-alpha, LPO, and NO were increased with advanced tumor stages. There
      were positive correlations between sFas, bcl-2, IL-8 TNF-alpha, LPO, and NO.
      CONCLUSIONS: BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth
      and survival. However, this coincides with activation of physiologic regulatory
      mechanisms, as increased IL-8, TNF-alpha, LPO, and NO, which try to stop tumor
      cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor
      progression as IL-8, TNF-alpha, and NO are also angiogenic stimulators.

PMID- 22362303
TI  - "Academic detailing" and "citizen science".

PMID- 22362302
TI  - Quantification of ZAP-70 mRNA by real-time PCR is a prognostic factor in chronic
      lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is heterogeneous with respect to
      prognosis and clinical outcome. Mutational status of immunoglobulin heavy chain
      variable region (IGHV) appears to be a particularly strong prognostic marker, but
      it is difficult to perform in a routine clinical laboratory. zeta-chain
      associated protein kinase 70 kDa (ZAP-70) protein detected by flow cytometry is a
      strong surrogate marker of IGHV mutational status; however, it suffers from the
      lack of standardization. METHODS: We investigated whether ZAP-70 mRNA expression
      level can be a prognostic factor in CLL. Real-time quantitative polymerase chain
      reaction was used to analyze ZAP-70 mRNA expression from 102 CLL patients.
      RESULTS: The expression of ZAP-70 mRNA was significantly associated with Binet
      stage (P < 0.001), lactate dehydrogenase (P = 0.003), ZAP-70 protein (P = 0.018),
      IGHV mutational status (P = 0.038), and cytogenetic abnormality of del(17p13) or
      del(11q22.3) (P = 0.037) in CLL patients. According to receiver operating
      characteristic curve analysis for ZAP-70 mRNA and ZAP-70 protein, positive ZAP-70
      mRNA (P = 0.006) was an adverse factor in determining the treatment free survival
      (TFS). In a multivariate Cox analysis of TFS, ZAP-70 mRNA is not ideal as an
      independent prognostic factor. However, ZAP-70 mRNA was statistically significant
      in predicting treatment response. CONCLUSION: This study demonstrated the value
      of determination of ZAP-70 mRNA in providing useful prognostic information in CLL
      patients. However, ZAP-70 mRNA is not an independent prognostic factor.

PMID- 22362305
TI  - Rational design of the nanowall photoelectrode for efficient solar water
      splitting.
AB  - The alternate dielectric component is introduced into a nanowall skeleton for the
      first time. As a photoelectrode, this novel model can optimize the process of
      photon absorption, charge separation/migration and surface reaction, resulting in
      superior photoelectrochemical performance.

PMID- 22362306
TI  - Tumour immunology: A close-range dual hit for tumour immunity.

PMID- 22362307
TI  - Two molecular weight species of thrombospondin-2 are present in bone and
      differentially modulated in fractured and nonfractured tibiae in a murine model
      of bone healing.
AB  - We report two immuoreactive species of thrombospondin-2 (TSP2), sized
      approximately 200 and 125 kDa, in the long bones of growing, but not skeletally
      mature, mice. In vitro osteoblasts secrete a 200-kDa species into the culture
      medium as early as day 3, and it appears in the cell-matrix layer by day 7. A 125
      kDa species appears in the cell-matrix layer in parallel with mineralization; it
      is not detected in cell-conditioned medium. Unilateral tibial fracture induced a
      time-dependent upregulation of the 200-kDa species at the site of trauma. By
      contrast, relative levels of the 125-kDa species at the fracture site were lower
      than in bones from naive control animals. In the contralateral untouched control
      tibia, the 200-kDa species was rapidly and substantially reduced compared to bone
      harvested from naive control mice. Levels of the 125-kDa species in the untouched
      tibia declined gradually with time postfracture. TSP2 gene expression in
      uninjured control bone decreased modestly by 21 days postfracture. On the day of
      fracture, the osteoblast differentiation potential of MSCs harvested from
      uninjured bones decreased compared to those harvested from naive control animals.
      The presence of two isoforms suggests that TSP2 may undergo posttranscriptional
      or posttranslational processing in skeletal tissue. Our data also suggest that,
      in the context of trauma, the two TSP2 isforms are differentially modulated at
      injured and noninjured skeletal sites in an animal undergoing fracture healing.

PMID- 22362308
TI  - Nitric oxide release: part III. Measurement and reporting.
AB  - Nitric oxide's expansive physiological and regulatory roles have driven the
      development of therapies for human disease that would benefit from exogenous NO
      administration. Already a number of therapies utilizing gaseous NO or NO donors
      capable of storing and delivering NO have been proposed and designed to exploit
      NO's influence on the cardiovascular system, cancer biology, the immune response,
      and wound healing. As described in Nitric oxide release: Part I. Macromolecular
      scaffolds and Part II. Therapeutic applications, the preparation of new NO
      release strategies/formulations and the study of their therapeutic utility are
      increasing rapidly. However, comparison of such studies remains difficult due to
      the diversity of scaffolds, NO measurement strategies, and reporting methods
      employed across disciplines. This tutorial review highlights useful analytical
      techniques for the detection and measurement of NO. We also stress the importance
      of reporting NO delivery characteristics to allow appropriate comparison of NO
      between studies as a function of material and intended application.

PMID- 22362309
TI  - All-cause cancer mortality over 15 years in multi-ethnic Mauritius: the impact of
      diabetes and intermediate forms of glucose tolerance.
AB  - There are accumulating data describing the association between diabetes and
      cancer mortality from Westernised populations. There are no data describing the
      relationship between diabetes and cancer mortality in African or South Asian
      populations from developing countries. We explored the relationship of abnormal
      glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic
      cohort from the developing nation of Mauritius. Population-based surveys were
      undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South
      Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's
      proportional hazards model with time varying covariates was used to obtain hazard
      ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality,
      after adjustment for confounding factors. In men, but not women, cancer mortality
      risk increased with rising 2h-PG levels with HR for the top versus bottom
      quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a
      significantly greater risk of cancer mortality than those with normal glucose
      tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance
      was associated with an elevated risk of cancer mortality compared to NGT (HR:
      1.47, 95% CI: 0.98-2.19), though this was not significant. We have shown that the
      association between abnormal glucose tolerance and cancer extends to those of
      African and South Asian descent. These results highlight the importance of
      understanding this relationship in a global context to direct future health
      policy given the rapid increase in type 2 diabetes, especially in developing
      nations.

PMID- 22362310
TI  - Perceptions of risk may explain the discrepancy between patient and clinician
      recorded symptoms.

PMID- 22362311
TI  - Oral immunotherapy for peanut allergy: an evidence-based  medicine assessment.

PMID- 22362312
TI  - Lower respiratory tract infection in the community: prognosis  predictably
      difficult to predict.

PMID- 22362313
TI  - Isolation of a gene encoding for a class III peroxidase in female flower of
      Corylus avellana L.
AB  - Hazelnut is a monoecious species characterized by mid-winter blooming and
      sporophytic incompatibility. The molecular mechanisms at the basis of the female
      flower development and of the pollen-stigma interaction are little known,
      although pollination in this species is a critical factor to ensure good yield.
      Differential display technique was used to study genes expressed during the
      female flower development, comparing styles before emergence from the bud and
      styles at full bloom. The full-length cDNA clone, designated CavPrx (Corylus
      avellana peroxidase) and isolated in mature styles, was characterized as a
      sequence encoding for a 330 amino acids protein, containing all the conserved
      features of class III peroxidases. CavPrx resulted expressed only in styles, with
      a peak in mature styles pollinated with compatible pollen. Class III peroxidases
      are expressed in several different plant tissue types and are involved in a broad
      spectrum of physiological processes. Until now, four peroxidases expressed in the
      stigma were identified in Arabidopsis thaliana and Senecio squalidus: they were
      assumed to be possibly involved in pollen-pistil interaction, pollen tube
      penetration/growth and/or in defence against pathogens. CavPrx is the first gene
      for a floral peroxidase isolated in hazelnut and its expression pattern suggests
      a possible role in the pollination process.

PMID- 22362314
TI  - Identification and characterization of selenate- and selenite-responsive genes in
      a Se-hyperaccumulator Astragalus racemosus.
AB  - Plants with capacity to accumulate high levels of selenium (Se) are desired for
      phytoremediation and biofortification. Plants of genus Astragalus accumulate and
      tolerate high levels of Se, but their slow growth, low biomass and non-edible
      properties limit their direct utilization. Genetic engineering may be an
      alternative way to produce edible or high biomass Se-accumulating plants. The
      first step towards this goal is to isolate genes that are responsible for Se
      accumulation and tolerance. Later, these genes can be introduced into other
      edible and high biomass plants. In the present study, we applied fluorescent
      differential display to analyze the transcript profile of Se-hyperaccumulator A.
      racemosus treated with 20 MUM selenate (K(2)SeO(4)) for 2 weeks. Among 125
      identified Se-responsive candidate genes, the expression levels of nine were
      induced or suppressed more than twofold by selenate treatment in two independent
      experiments while 14 showed such changes when treated with selenite (K(2)SeO(3)).
      Six of them were found to respond to both selenate and selenite treatments. A
      novel gene CEJ367 was found to be highly induced by both selenate (1,920-fold)
      and selenite (579-fold). Root- or shoot-preferential expression of nine genes was
      further investigated. These identified genes may allow us to create Se-enriched
      transgenic plants.

PMID- 22362316
TI  - Perinatal transmission of hepatitis C virus in northern India.
AB  - Data on transmission of HCV infection from mother to infant in India are limited.
      Between July 2006 to June 2007, women attending our hospital in the third
      trimester of pregnancy were screened for anti-HCV. Those testing positive for
      anti-HCV were tested for HCV RNA. Infants of mothers with HCV infection were
      followed for up to 24 months. Eight of 488 pregnant women (1.6%) tested positive
      for anti-HCV; of these, seven had detectable HCV RNA. Two of 7 (29%) children
      born to HCV-infected mothers had persistently positive HCV RNA, indicating
      perinatal transmission; one additional child had transient HCV positivity.
      Passive transfer of HCV antibodies was observed in five babies. HCV infection was
      detected in 1.4% of pregnant women, and perinatal transmission of HCV to newborns
      was detected in 29% of such cases.

PMID- 22362317
TI  - Primary iron overload and HFE gene mutations in North Indian adults.

PMID- 22362320
TI  - Applying systemic functional linguistics to conversations with dementia: the
      linguistic construction of relationships between participants.
AB  - Social isolation in dementia is a growing concern as the incidence and prevalence
      of dementing conditions is on the rise in many societies. Positive social
      interactions, which foster the construction and enactment of positive
      interpersonal relationships and therefore positive discursive identities, make an
      important contribution to emotional well-being. In this article, we investigate
      how two women diagnosed with dementia of the Alzheimer's type use language to
      relate to each other and two visiting graduate students. We use Systemic
      Functional Linguistics as an analytical framework, specifically investigating the
      use of vocatives and naming, and conversational moves and exchanges.

PMID- 22362321
TI  - Expressing opinions and feelings in a conversational setting.
AB  - This article examines the ways in which individuals with aphasia communicate
      opinions and feelings using evaluative language during conversation in an aphasia
      group. Evaluative language refers to semantic resources conveying emotions,
      judgments, and valuations and includes emotive adjectives, nouns, verbs, and
      adverbs as well as metaphor. Although individuals with aphasia are known to be
      able to use evaluative language in a monologic context, little is known about how
      people with aphasia use evaluative language in conversation, or about the role of
      co-construction in such usage. The data for this study were collected during a
      conversation group consisting of five participants with aphasia and a
      facilitator. The analysis used is based on Appraisal theory (Martin and White
      2005) and examined the evaluation categories of Affect, Appreciation, Judgment,
      and Graduation. Regardless of severity, all aphasic speakers contributed an equal
      amount of evaluation to the interaction and demonstrated some usage of all types
      of evaluation. However, those with more severe aphasia relied heavily on their
      conversational partners to scaffold their opinions and used a range of resources
      including lexical items, such as exactly, and repetition (e.g., "yeah yeah yeah")
      to agree emphatically with opinions expressed. Lexical variety was notably less
      in the aphasic speakers than the non-brain-damaged group facilitator. The article
      discusses the patterns of skills observed together with the clinical implications
      for working with people with aphasia on emotional meanings.

PMID- 22362322
TI  - Potential causes and consequences of overlap in talk between speakers with
      Parkinson's disease and their familiar conversation partners.
AB  - Parkinson's disease (PD) can cause both motor speech and cognitive deficits, with
      those affected perceiving a negative effect on their everyday experiences of
      communication. One specific concern reported by people with PD is that people
      "talk over" them. Psychosocial reactions to communication changes in PD are
      highly individualized and do not correlate strongly with measures of disease
      severity. With the aim of developing a better understanding of the individual's
      everyday experience of being talked over, this study uses Conversation Analysis
      to examine videoed instances of naturally occurring overlapping talk. Two
      phenomena emerge. First, aspects of speech specific to PD can cause overlap,
      which in turn leads to the need for repair. Second, opportunities to repair
      disordered talk, further compromised in terms of intelligibility by overlap, are
      often not followed up. This leads to the deletion of PD turns at talk and
      therefore reduced participation in conversations. The implications of these
      phenomena for both client well-being and clinical interventions are discussed.

PMID- 22362324
TI  - Analysis of narrative functionality: toward evidence-based approaches in managed
      care settings.
AB  - The advent of managed health care has challenged rehabilitation professionals to
      guide their clients toward functionally meaningful outcomes in the least amount
      of time possible and to justify the evidence base for their intervention
      approaches. The ability to relate personal narratives in everyday contexts lies
      at the core of communicative functionality, but feasible clinical assessment of
      narrative has proven elusive. The purpose of this article is to offer an evidence
      based framework for guiding assessments of the personal narratives of adults with
      aphasia, within a managed care model of service delivery. A literature-based
      model of narrative functionality is proposed, and a targeted set of criterion
      referenced measures and behavioral observations derived from this model are
      suggested as potential metrics of narrative functionality. The authors do not
      intend to prescribe exact methods of narrative evaluation, but rather to suggest
      possible directions for professionals to develop evidence-based clinical
      narrative analysis tailored to the functional assessment needs of their clients
      across a variety of service settings.

PMID- 22362323
TI  - Beyond utterances: distributed cognition as a framework for studying discourse in
      adults with acquired brain injury.
AB  - Considerable effort has been directed at understanding the nature of the
      communicative deficits observed in individuals with acquired brain injuries. Yet
      several theoretical, methodological, and clinical challenges remain. In this
      article, we examine distributed cognition as a framework for understanding
      interaction among communication partners, interaction of communication and
      cognition, and interaction with the environments and contexts of everyday
      language use. We review the basic principles of distributed cognition and the
      implications for applying this approach to the study of discourse in individuals
      with cognitive-communication disorders. We also review a range of protocols and
      findings from our research that highlight how the distributed cognition approach
      might offer a deeper understanding of communicative mechanisms and deficits in
      individuals with cognitive communication impairments. The advantages and
      implications of distributed cognition as a framework for studying discourse in
      adults with acquired brain injury are discussed.

PMID- 22362325
TI  - Characteristics of narrative discourse processing after damage to the right
      hemisphere.
AB  - The narrative skills of nonaphasic individuals with right hemisphere damage (RHD)
      were compared with those of a group of healthy participants. All participants
      scored within the normal range on tests assessing their level of global cognitive
      impairment, logical visuospatial reasoning, general linguistic skills, and the
      potential presence of hemineglect. They were asked to describe the stories
      portrayed in a set of picture sequences. The individuals with RHD produced
      descriptions with normal levels of microlinguistic processing but with more
      tangential errors and conceptually incongruent utterances that lowered their
      levels of informativeness. A further analysis revealed that these deficits were
      most evident in persons with anterior lesions to the right hemisphere. These
      findings lend indirect support to the hypothesis of a major involvement of
      frontal right hemispheric areas to the process of organization of information in
      a narrative discourse.

PMID- 22362326
TI  - Longitudinal changes in discourse production in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a multisystem disease that significantly
      impacts communication as a function of changes in motor speech, cognition, and
      language skills. Although discourse tasks have been used to assess language in a
      variety of acquired disorders, little work to date has been published on changes
      in discourse in ALS and even less work has evaluated these changes with disease
      progression. In the present study, discourse samples (gained from a picture
      description task) as well as standardized language test measures obtained from 16
      individuals with ALS without dementia and 12 healthy controls (collected over a
      duration of 24 months). Discourse samples were analyzed for both productivity and
      content. Results indicate that there were no differences for ALS versus controls
      for any of the standardized language tests. However, findings suggest that
      discourse analysis methods may be more sensitive for identifying subtle language
      deficits in ALS. Overall, discourse productivity appears less impaired than
      discourse content for individuals with ALS. Although there was a general trend
      for decline in language performance over the study duration, there was the
      suggestion of subgroups of language performance among ALS participants. The
      results suggest that subtle cognitive language deficits that affect discourse
      emerge early in ALS and progress with disease progression.

PMID- 22362328
TI  - Peripheral T-cell lymphomas: diagnosis and treatment options. Proceedings from a
      live roundtable, August 17, 2011, Kauai, Hawaii.
AB  - Peripheral T-cell lymphomas are a collection of rare diseases, most of which have
      a poor prognosis. The basic categories include precursor lymphoid neoplasms (eg,
      lymphoblastic lymphoma); mature natural killer/T-cell neoplasms and extranodal
      lymphomas, including enteropathy-associated T-cell lymphoma; hepatosplenic T-cell
      lymphoma; and subcutaneous panniculitis-like T-cell lymphoma. The most common
      varieties are the nodal types, which include peripheral T-cell lymphoma not
      otherwise specified, anaplastic large cell lymphomas, and angioimmunoblastic T
      cell lymphomas. Each of the subtypes has characteristic clinical manifestations.
      The frequencies of the subtypes vary by geographic region. The diagnosis can be
      difficult, and the World Health Organization classification system was recently
      evaluated to assess its clinical applicability and reproducibility for peripheral
      T-cell lymphomas and natural killer/T-cell lymphomas. At least 10% of patients
      are incorrectly diagnosed by local laboratories, and many subtypes need better
      diagnostic markers and criteria. Currently, an increasing number of effective and
      tolerable therapies are becoming available, including pralatrexate, brentuximab
      vedotin, romidepsin, and bendamustine. Accurate diagnosis is necessary to allow
      appropriate treatment, as exemplified by patients with anaplastic large cell
      lymphoma that expresses high levels of CD30, who have high response rates to
      brentuximab vedotin. Patients with peripheral T-cell lymphoma should be enrolled
      in clinical trials when possible. New medications should be incorporated into
      therapies in well-designed clinical trials to develop appropriate safety and
      efficacy data.

PMID- 22362329
TI  - Ignoring overdispersion in hierarchical loglinear models: Possible problems and
      solutions.
AB  - Poisson data frequently exhibit overdispersion; and, for univariate models, many
      options exist to circumvent this problem. Nonetheless, in complex scenarios, for
      example, in longitudinal studies, accounting for overdispersion is a more
      challenging task. Recently, Molenberghs et.al, presented a model that accounts
      for overdispersion by combining two sets of random effects. However, introducing
      a new set of random effects implies additional distributional assumptions for
      intrinsically unobservable variables, which has not been considered before. Using
      the combined model as a framework, we explored the impact of ignoring
      overdispersion in complex longitudinal settings via simulations. Furthermore, we
      evaluated the effect of misspecifying the random-effects distribution on both the
      combined model and the classical Poisson hierarchical model. Our results indicate
      that even though inferences may be affected by ignored overdispersion, the
      combined model is a promising tool in this scenario.

PMID- 22362330
TI  - Melperone is ineffective in treating Parkinson's disease psychosis.

PMID- 22362331
TI  - Effects of long-term electromagnetic field exposure on spatial learning and
      memory in rats.
AB  - With the development of communications industry, mobile phone plays an important
      role in daily life. Whether or not the electromagnetic radiation emitted by
      mobile phone causes any adverse effects on brain function has become of a great
      concern. This paper investigated the effect of electromagnetic field on spatial
      learning and memory in rats. 32 trained Wistar rats were divided into two groups:
      exposure group and control group. The exposure group was exposed to 916 MHz,
      10w/m2 mobile phone electromagnetic field (EMF) 6 h a day, 5 days a week, 10
      weeks. The completion time, number of total errors and the neuron discharge
      signals were recorded while the rats were searching for food in an eight-arm
      radial maze at every weekend. The neuron signals of one exposed rat and one
      control rat in the maze were obtained by the implanted microelectrode arrays in
      their hippocampal regions. It can be seen that during the weeks 4-5 of the
      experiment, the average completion time and error rate of the exposure group were
      longer and larger than that of control group (p < 0.05). During the weeks 1-3 and
      6-9, they were close to each other. The hippocampal neurons showed irregular
      firing patterns and more spikes with shorter interspike interval during the whole
      experiment period. It indicates that the 916 MHz EMF influence learning and
      memory in rats to some extent in a period during exposure, and the rats can adapt
      to long-term EMF exposure.

PMID- 22362332
TI  - Cytoskeletal proteins in the cerebrospinal fluid as biomarker of multiple
      sclerosis.
AB  - The axonal cytoskeleton is a finely organized system, essential for maintaining
      the integrity of the axon. Axonal degeneration is implicated in the pathogenesis
      of unremitting disability of multiple sclerosis (MS). Purpose of this study is to
      evaluate levels of cytoskeletal proteins such as neurofilament light protein
      (NFL), glial fibrillary acidic protein (GFAP), and beta-tubulin (beta-Tub)
      isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their
      correlation with MS clinical indices. CSF levels of cytoskeletal proteins were
      determined in 51 patients: 33 with MS and 18 with other neurological diseases
      (OND). NFL, GFAP and beta-Tub II proteins were significantly higher (p < 0.0001)
      in MS than in OND group; no significant difference (p > 0.05) was found between
      MS and OND with regard to beta-Tub III. Interestingly, levels of beta-Tub III and
      NFL were higher in progressive than in remitting MS forms; on the contrary,
      higher levels of beta-Tub II and GFAP were found in remitting MS forms. However,
      with the exception of beta-Tub III, all proteins tend to decrease their CSF
      levels concomitantly with the increasing disability (EDSS) score. Overall, our
      results might indicate beta-Tub II as a potential candidate for diagnostic and
      beta-Tub III as a possible prognostic biomarker of MS. Therefore, further
      analyses are legitimated and desirable.

PMID- 22362333
TI  - Mug20, a novel protein associated with linear elements in fission yeast meiosis.
AB  - In the fission yeast, Schizosaccharomyces pombe, homologous chromosomes
      efficiently pair and recombine during meiotic prophase without forming a
      canonical synaptonemal complex (SC). Instead, it features simpler filamentous
      structures, the so-called linear elements (LinEs), which bear some resemblance to
      the axial/lateral element subunits of the SC. LinEs are required for wild-type
      recombination frequency. Here, we recognized Mug20, the product of a meiotically
      upregulated gene, as a LinE-associated protein. GFP-tagged Mug20 and anti-Mug20
      antibody co-localized completely with Rec10, one of the major constituents of
      LinEs. In the absence of Mug20, LinEs failed to elongate beyond their initial
      state of nuclear dots. Foci of recombination protein Rad51 and genetic
      recombination were reduced. Since meiotic DNA double-strand breaks (DSBs), which
      initiate recombination, are induced at sites of preformed LinEs, we suggest that
      reduced recombination is a consequence of incomplete LinE extension. Therefore,
      we propose that Mug20 is required to extend LinEs from their sites of origin and
      thereby to increase DSB proficient regions on chromosomes.

PMID- 22362334
TI  - Magnetic enzyme nanogel (MENG): a universal synthetic route for biocatalysts.
AB  - A universal synthetic route for magnetic enzyme nanogels (MENGs) was proposed,
      based on electrostatic interaction driven assembly and in situ polymerization
      from the surface of magnetic nanoparticles, to avoid chemical modification of
      proteins and hence structural and functional deterioration.

PMID- 22362336
TI  - Dental management of patients before and after renal transplantation.
AB  - The number of patients who are long-term survivors of renal transplantation
      increases rapidly, and proportionally increases the demand of quality dental care
      for this group of patients. All the transplant patients are on potent
      immunosupressants and also some of them may suffer from other systemic diseases,
      so their dental management is a challenge for any dentist. This article is an
      update of the current relevant literature and is aimed to summarize the key
      points of dental care for renal transplant patients, since no specific guidelines
      exist. The research for relevant references took place by using Pubmed database,
      as well as information published by accredited medical societies and health
      services both in Greece and abroad.

PMID- 22362337
TI  - Factors influencing face aging. Literature review.
AB  - The aim of this review is to analyze different factors which can affect natural
      face aging by delaying or expediting the process. Various studies shows that
      different factors such as ultraviolet light, gravity, habits, teeth loss may
      affect face appearance during aging. The articles from 1959 to 2011 related to
      topic were identified. 47 articles were selected for data collection.

PMID- 22362335
TI  - Cocaine-using patients with a normal or nondiagnostic electrocardiogram: single
      photon emission computed tomography myocardial perfusion imaging and outcome.
AB  - BACKGROUND: Few trials have examined the outcomes of patients who use cocaine
      with chest pain and who have a normal or nondiagnostic electrocardiogram (ECG)
      and the use of single-photon emission computed tomography (SPECT) myocardial
      perfusion imaging (MPI). HYPOTHESIS: We sought to compare the characteristics and
      overall outcomes in cocaine users vs non-cocaine users presenting to the
      emergency department with a normal/nondiagnostic ECG and to assess the value of
      rest MPI in both of these populations. METHODS: Patients with symptoms compatible
      with myocardial ischemia, suspected acute coronary syndrome (ACS), and a
      normal/nondiagnostic ECG were enrolled in the Emergency Room Assessment of
      Sestamibi for Evaluation of Chest Pain (ERASE Chest Pain) trial, a randomized
      controlled trial designed to evaluate the impact of rest MPI on triage decisions.
      Cocaine users (n = 294) were compared to non-cocaine users (n = 2180). Cocaine
      users were younger than non-cocaine users, and 72% were male. RESULTS: Among the
      cocaine users, 2.4% had a myocardial infarction, 1.4% required percutaneous
      coronary intervention, and none of the patients underwent coronary artery bypass
      graft surgery. Among cocaine users with a final diagnosis of not ACS,
      randomization of patients to rest SPECT MPI resulted in an appropriate reduction
      in hospital admissions in both the cocaine users (P = 0.011) and the non-cocaine
      users (P < 0.001), suggesting improved triage when MPI was used. CONCLUSIONS:
      Cocaine users with a normal/nondiagnostic ECG are at low risk of cardiac events.
      Even though cocaine users are at low risk of cardiac events, SPECT MPI remains
      effective in the risk stratification and improves triage management decisions
      resulting in lower admission rates and more discharges to home.

PMID- 22362338
TI  - Specific signaling molecule expression in periodontal ligaments in different age
      groups: pilot study.
AB  - INTRODUCTION. Orthodontic teeth movement is accompanied by remodeling of alveolar
      bone, including the interradicular septum and periodontal ligaments (PDL).
      Periodontal signaling molecules have important functions during tooth movement
      and they are active in the bone remodeling process. Patients involved in
      orthodontic treatment belong to different age groups: therefore age must be
      considered as a contributing factor compromising the remodeling potential of
      periodontal tissues. The aim of the current study was to investigate the specific
      expression of signaling molecules in the PDL of interradicular septum in patients
      from different groups of age. MATERIALS AND METHODS. The study group included 25
      patients to whom extractions of teeth was recommended as a part of further
      orthodontic treatment. 25 patients (10 males and 15 females) were divided into
      three groups as follows: 1) 12-14 years old; 2) 15-22 years old; and 3) 23 years
      old or older. The routine histological method was followed and samples were
      stained with hematoxyline-eosine. According to literature data in current
      immunohistochemical study were included and examined expression of NGFR (nerve
      growth factor receptor), TGF-beta (transforming growth factor beta), bFGF (basic
      fibroblast growth factor), FGFR1 (fibroblast growth factor receptor), IL-1
      (interleukin 1), IL-6 (interleukin 6), IL-8 (interleukin 8), MMP-1 (matrix
      metalloproteinase 1), MMP-2 (matrix metalloproteinase 2), MMP-8 (matrix
      metalloproteinase 8), MMP-9 (matrix metalloproteinase 9), MMP-13 (matrix
      metalloproteinase 13) in PDL of interradicular septum. The distribution of these
      factors was evaluated semi quantitatively. RESULTS. Expression levels of FGFR1,
      bFGF, MMP 8 and 9, and IL-6 in PDL of interradicular septum structure were
      determined in all samples. Decreases in the mean values of signaling factors
      relevant to age were statistically significant in bFGF. CONCLUSIONS. Analyzed
      data suggest that bFGF, FGFR, IL-6, MMP 8 and 9 were determined as signaling
      factors in PDL of interradicular septum. Mean expression level decrease with age
      of FGFR1, IL-6, MMP-8, MMP-9 was non- statistically significant. The mean
      expression level of bFGF decreased with age, and this decrease was statistically
      significant. In younger patients, signal molecule expression is higher because of
      increased PDL metabolic activity. Increased PDL metabolic activity is a reason
      for higher expression of signal molecule in younger patients. Activity of
      remodeling process of periodontal tissue decreases with the aging and expression
      of signaling molecule decreases in adults.

PMID- 22362339
TI  - Upper airway sagittal dimensions in obstructive sleep apnea (OSA) patients and
      severity of the disease.
AB  - OBJECTIVES. To estimate the soft tissue determined individual features of the
      upper airway sagittal size which may predispose the patient to snoring and OSA
      and to find whether there is any relationship between the patient's body-mass
      index (BMI) and the severity of OSA. MATERIAL AND METHODS. 58 consecutive
      patients with a mean age of 33.4 years were surgically treated for snoring and
      OSA. Before the operation they were subject to the following: physical
      examination, a sleep study to determine the severity of sleep disturbed breathing
      (SDB); the body mass index (BMI) was calculated, lateral cephalometry (LC) was
      recorded. RESULTS. Snoring was found in 25 patients, OSA I (mild) - 15, OSA II
      (moderate) - 9, OSA III (severe) - in 9 patients. Among patients with obesity,
      the most widespread types of sleep disorders were OSA II and OSA III. (p=0.029).
      There were differences in the mean values of the BMI between the group of snorers
      and the group with OSA II (p=0.007), between snorers and OSA III (p=0.006).
      Differences in upper airway cephalometric mean values between groups were found,
      the thickness of the uvula (SPT) between snorers and OSA III (p=0.001), between
      the OSA I and OSA III groups (p=0.032), and between the OSA II and OSA III groups
      (p=0.075). CONCLUSION. Our study found narrowing in the anterior-posterior
      dimension of the airway at all levels, correlating with the severity of OSA as
      well as the BMI. The narrowest place was found in the oropharynx with an
      extension to the hypopharynx.

PMID- 22362340
TI  - Endoscopically assisted enucleation of a large mandibular periapical cyst.
AB  - Enucleation of large cysts in the jaws is an invasive method that might be
      associated with complications. Marsupialization is a less invasive alternative
      method but it involves a prolonged and uncomfortable healing period. This study
      addresses a contemporaneous and less invasive surgical technique for treating
      larger mandibular cysts. MATERIALS AND METHODS. A 48-year-old woman presented
      with a large mandibular apical cyst involving the left parasymphysis, body, ramus
      and condylar neck, with involvement of the alveolar inferior nerve. The cystic
      lesion was enucleated using a 30 degrees  4.0 mm endoscopic scope and endoscopic
      instruments through two small accesses: the ostectomy site of previously
      performed marsupialization and the alveolus of the involved third molar extracted
      of the time of the enucleation of the cyst. RESULTS. The endoscopic scope
      provided good visualization of the whole cystic cavity allowing the removal of
      any residual pathologic tissue and preservation of the integrity of the involved
      inferior alveolar nerve. The morbidity of the surgical procedure was extremely
      reduced. At a 6-month follow-up the patient did not present any symptom of
      inflammation and a panoramic X-ray showed good bone repair and remodelation.
      CONCLUSIONS. Endoscopically assisted enucleation proved to be effective method of
      treating a large mandibular cyst, providing total enucleation with a minimal
      invasive technique.

PMID- 22362341
TI  - Squamous cell carcinoma of the left temporal region.
AB  - Clinical case is about squamous cell carcinoma in region of face and head.
      Patient was diagnosed with 6-7 cm tumor in region of temple in the left side of
      the face. Patient took his first medical advice after 8 years then he felt first
      symptoms. After full examination of a patient there was decided to eradicate the
      tumor radically and reconstruct the defect primarily with skin graft. In a three
      months after the operation good esthetic effect is visible. Patient was send to a
      local doctor for a regular observation because of possible recurrence. No data of
      recurrence, during two years of regular observation, was given.

PMID- 22362343
TI  - A question of stability and commitment.

PMID- 22362342
TI  - Potentially inappropriate medications in the elderly: a comprehensive protocol.
AB  - Elderly patients are at increased risk of drug-related morbidity and mortality.
      Avoiding the use of potentially inappropriate medications (PIMs) is one of the
      strategies that has been widely adopted to reduce the harmful consequences of
      drug use. There are several PIM screening tools available. In this review, we
      provide an overview of existing screening tools to detect PIMs in the elderly,
      emphasizing the advantages and disadvantages of each. Combining previously
      published and adopted tools (adjusted Beers list, French consensus panel,
      McLeod's list, and Lindblad's list of clinically important drug-disease
      interactions), we develop a new comprehensive tool that also includes the
      adjusted Hanlon's and Malone's lists of potentially serious drug-drug
      interactions in the elderly. In addition to listed PIMs and clinically important
      drug-drug interactions, alternative therapeutic solutions are suggested. The new
      protocol differentiates: drugs with an unfavorable benefit/risk ratio (to be
      avoided regardless of the underlying disease/condition), drugs with a
      questionable efficacy, and drugs to be avoided with certain diseases/conditions,
      and provides a list of potentially serious drug-drug interactions. A tool
      consisting of PIMs and potential drug-drug interactions within the same protocol
      provides more comprehensive quality assessment of drug-prescribing behavior to
      the elderly, which in turn may lead to better prescribing practices.

PMID- 22362347
TI  - A division of labour.

PMID- 22362351
TI  - ADAM17 -- gatekeeper of the skin barrier.

PMID- 22362352
TI  - Balancing the books.

PMID- 22362354
TI  - Beyond pattern recognition: five immune checkpoints for scaling the microbial
      threat.
AB  - Pattern recognition by the innate immune system enables the detection of
      microorganisms, but how the level of microbial threat is evaluated - a process
      that is crucial for eliciting measured antimicrobial responses with minimal
      inflammatory tissue damage - is less well understood. New evidence has shown that
      features of microbial viability can be detected by the immune system and thereby
      induce robust responses that are not warranted for dead microorganisms. Here, we
      propose five immune checkpoints that, as defined here, collectively determine the
      gravity of microbial encounters.

PMID- 22362356
TI  - Translating cancer prevention and control research into the community setting:
      workforce implications.
AB  - A gap exists between cancer prevention research and its translation into
      community practice. Two strategies to reduce this gap are community-based
      participatory research (CBPR) and dissemination research. CBPR offers an avenue
      to engage academic and community partners, thereby providing mechanisms for joint
      learning and application of knowledge. Dissemination research examines the
      movement of evidence-based public health and clinical innovations to practice
      settings. While applying these approaches may reduce the gap between research and
      practice, the cancer prevention workforce may be inadequate in size,
      insufficiently trained, lack resources and incentives, or face structural
      barriers to effectively participate in CBPR and disseminate evidence-based
      research findings into practice. Information on translating cancer prevention
      information to communities and workforce implications was obtained from a panel
      of experts and through a review of the literature on CBPR and dissemination
      research. The expert panel and literature review identified major barriers to
      successfully conducting CBPR and dissemination research in community settings.
      Barriers included inadequate policies; insufficient networking and communication
      infrastructures; unsupportive research cultures, climates, and mindsets;
      inadequate researcher and practitioner education; and limited CBPR and
      dissemination research with adequate study designs. No specific estimates of the
      cancer prevention workforce were found; however, indirect evidence for a
      shortfall were identified. We recommend expanding CBPR training for academic and
      community partners; increasing funding for dissemination research and practice;
      supporting proven partnerships; and providing strategic coordination for
      government agencies, research institutions, nongovernmental organizations, and
      the private sector to foster better dissemination of information and integration
      of community-based cancer prevention and control programs and practices. Specific
      challenges and needs that must be addressed to improve the translation of cancer
      prevention research into community settings were identified.

PMID- 22362355
TI  - Nitric oxide release: part I. Macromolecular scaffolds.
AB  - The roles of nitric oxide (NO) in physiology and pathophysiology merit the use of
      NO as a therapeutic for certain biomedical applications. Unfortunately, limited
      NO payloads, too rapid NO release, and the lack of targeted NO delivery have
      hindered the clinical utility of NO gas and low molecular weight NO donor
      compounds. A wide-variety of NO-releasing macromolecular scaffolds has thus been
      developed to improve NO's pharmacological potential. In this tutorial review, we
      provide an overview of the most promising NO release scaffolds including protein,
      organic, inorganic, and hybrid organic-inorganic systems. The NO release vehicles
      selected for discussion were chosen based on their enhanced NO storage, tunable
      NO release characteristics, and potential as therapeutics.

PMID- 22362357
TI  - A deuterated analog of dasatinib disrupts cell cycle progression and displays
      anti-non-small cell lung cancer activity in vitro and in vivo.
AB  - The pan-Src family kinase inhibitor dasatinib has been approved for chronic
      myeloid leukemia treatment but displays limited activity in lung cancer patients.
      In this study, we used a deuterium substitution strategy to develop a class of
      novel chemicals based on dasatinib and found that these compounds maintain
      inhibition on c-Src activity and display anti-non-small cell lung cancer activity
      in vitro and in vivo. BRP800, one of these compounds, was chosen for further
      studies. BRP800 mainly displayed antiproliferative but not proapoptotic activity.
      Molecularly, BRP800 did not show significant effects on the expression of
      antiapoptotic genes, such as Bcl-2 and Mcl1, or on the activation of apoptotic
      enzymes, such as caspase-3, -8 or 9. However, BRP800 decreased expression of cell
      cycle promoting genes such as cyclins D1, D3, E, A and CDK4 and 6, and increased
      the expression of cell cycle negative regulators including p21, p27 and p53.
      Consistent with these findings, BRP800 arrested cells at the G0/G1 phase in a
      concentration-dependent manner, and the G0/G1 fraction was increased from 64% in
      control to 85% in BRP800-treated cells. We also evaluated the effects of BRP800
      on NSCLC xenografts using H460 as a model in nude mice. Compared with the known
      NSCLC drug docetaxel, BRP800 displayed potent and similar antitumor activity but
      with less toxicity. These findings suggest that the deuterated analog of
      dasatinib is antiproliferative by inhibiting c-Src and disrupting cell cycle
      progression, and could be further developed as a novel drug for non-small lung
      cancer treatment.

PMID- 22362353
TI  - Living in the liver: hepatic infections.
AB  - The liver has vital metabolic and clearance functions that involve the uptake of
      nutrients, waste products and pathogens from the blood. In addition, its unique
      immunoregulatory functions mediated by local expression of co-inhibitory
      receptors and immunosuppressive mediators help to prevent inadvertent organ
      damage. However, these tolerogenic properties render the liver an attractive
      target site for pathogens. Although most pathogens that reach the liver via the
      blood are eliminated or controlled by local innate and adaptive immune responses,
      some pathogens (such as hepatitis viruses) can escape immune control and persist
      in hepatocytes, causing substantial morbidity and mortality worldwide. Here, we
      review our current knowledge of the mechanisms of liver targeting by pathogens
      and describe the interplay between pathogens and host factors that promote
      pathogen elimination and maintain organ integrity or that allow pathogen
      persistence.

PMID- 22362359
TI  - Hydro-ionothermal syntheses, crystal structures, and properties of five new
      divalent metal iminophosphonates.
AB  - The use of a moderately hydrophobic ionic liquid, 1-butyl-2,3-dimethylimidazolium
      tetrafluoroborate ([BdMIM][BF(4)]), as a cosolvent with water, has been
      investigated in the synthesis of metal phosphonates. This hydro-ionothermal
      synthesis has been carried out through a systematic combinatorial investigation
      of several divalent metal chlorides and two related ligands,
      iminobis(methylphosphonic acid) and N-methyliminiobis(methylphosphonic acid).
      These reactions resulted in five new divalent metal phosphonates. We present here
      the synthetic techniques utilized as well as the X-ray structures and
      characteristic properties of each of these compounds.
      Co(HO(3)PCH(2)NH(2)CH(2)PO(3)H)(2), (1), consists of sheets that are hydrogen
      bonded together by pairs of P-O...H groups.
      Co(H(2)O)(2)(HO(3)PCH(2)NH(2)CH(2)PO(3)H)(2), (2), consists of chains that are
      connected through an extensive network of hydrogen bonds.
      Co(HO(3)PCH(2)NH(CH(3))CH(2)PO(3)H)(2), (3), is made up of sheets that are
      hydrogen bonded together by pairing P-O...H interactions.
      Zn(3)(O(3)PCH(2)NH(2)CH(2)PO(3))(2), (4), is isostructural to a previously
      reported cobalt compound which is a non-porous 3-dimensional network.
      CuClPO(3)CH(2)NH(2)CH(3), (5), formed as a result of an in situ N-C bond
      cleavage. Ladders built of Cu-O-P-O 8-membered rings are crosslinked by bridging
      chloride atoms to form sheets. 1, 3, 4 and 5 have been synthesized using the
      hydrophobic ionic liquid 1-butyl-2,3-dimethylimidazolium tetrafluoroborate
      ([BdMIM][BF(4)]) with water as a cosolvent, while 2 has been synthesized from
      identical conditions in the absence of the [BdMIM][BF(4)]. We also report the
      microwave assisted hydro-ionothermal synthesis of the known polymorph of 2,
      Co(H(2)O)(2)(HO(3)PCH(2)NH(2)CH(2)PO(3)H)(2), (6), synthesized in two hours
      providing high quality crystals in good yield. The compounds have been
      characterized by thermogravimetric analysis and IR spectroscopy, and their
      magnetic properties have been investigated.

PMID- 22362360
TI  - [Five years after the new further education legislation (WBO 2005): experience
      from the seminar basic surgery, common trunk in Bielefeld].

PMID- 22362358
TI  - Immunological heterogeneity of the RCC microenvironment: do targeted therapies
      influence immune response?
AB  - The introduction of targeted agents has substantially improved treatment of
      metastatic clear-cell renal cell carcinoma (RCC). However, complete responses are
      rare and therapy is not curative. Moreover, information on the latest generation
      of potent and selective vascular endothelial growth factor receptor (VEGFR)
      tyrosine kinase inhibitors (TKI) suggests that a plateau has been reached in
      terms of efficacy. Recent data reveal that targeted agents are involved in
      modulating immune responses in RCC. In addition, current research adds to our
      understanding of how RCC escapes an effective anti-tumor response with the
      potential to modulate these processes by drug development. This review provides
      specific insight into targeted therapy induced changes in the immunological
      microenvironment of RCC, summarizes the available evidence, and discusses
      potential therapeutic implications.

PMID- 22362361
TI  - Investigating the reaction mechanism and organocatalytic synthesis of
      alpha,alpha'-dihydroxy ketones.
AB  - A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate
      alpha,alpha'-dihydroxy ketones in water has recently been described. To
      investigate this tertiary-amine mediated reaction mechanism two approaches were
      used. Firstly, (13)C labelled lithium hydroxypyruvate was synthesised and used to
      establish where hydroxypyruvate is incorporated in the product. In separate
      experiments reaction intermediates were also successfully intercepted and
      structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS.
      These studies indicated that two mechanisms appear to be operating, one involving
      the addition of the tertiary amine catalyst to hydroxypyruvate, the other an
      aldol-based mechanism. Since the first mechanism may enable facial
      stereodifferentiation in the addition of intermediates to the aldehyde, a
      preliminary study on the use of chiral catalysts was performed and the first
      asymmetric organocatalytic synthesis of alpha,alpha'-dihydroxy ketones in aqueous
      media achieved, in up to 50% ee, using a quinine ether catalyst.

PMID- 22362362
TI  - ROS constitute a convergence nexus in the development of IGF1 resistance and
      impaired wound healing in a rat model of type 2 diabetes.
AB  - An indolent non-healing wound and insulin and/or insulin-like growth factor
      (IGF1) resistance are cardinal features of diabetes, inflammation and
      hypercortisolemia. Little is known about why these phenomena occur in so many
      contexts. Do the various triggers that induce insulin and/or IGF1 resistance and
      retard wound healing act through a common mechanism? Cultured dermal fibroblasts
      from rats and full-thickness excisional wounds were used as models to test the
      premise that reactive oxygen species (ROS) play a causal role in the development
      of IGF1 resistance and impaired wound healing under different but
      pathophysiologically relevant clinical settings, including diabetes,
      dexamethasone-induced hypercortisolemia and TNFalpha-induced inflammation. In
      normal fibroblasts, IGF1 initiated a strong degree of phosphorylation of insulin
      receptor substrate 1 (IRS1) (Tyr612) and Akt (Ser473), concomitantly with
      increased PI3K activity. This phenomenon seemed to be attenuated in fibroblasts
      that had phenotypic features of diabetes, inflammation or hypercortisolemia.
      Notably, these cells also exhibited an increase in the activity of the ROS
      phospho-JNK (p-JNK)-p-IRS1 (Ser307) axis. The above-mentioned defects were
      reflected functionally by attenuation in IGF1-dependent stimulation of key
      fibroblast functions, including collagen synthesis and cell proliferation,
      migration and contraction. The effects of IGF1 on glucose disposal and cutaneous
      wound healing were also impaired in diabetic or hypercortisolemic rats. The ROS
      suppressors EUK-134 and alpha-lipoic acid, or small interfering RNA (siRNA)
      mediated silencing of JNK expression, restored IGF1 sensitivity both in vitro and
      in vivo, and also ameliorated the impairment in IGF1-mediated wound responses
      during diabetes, inflammation and hypercortisolemia. Our data advance the notion
      that ROS constitute a convergence nexus for the development of IGF1 resistance
      and impaired wound healing under different but pathophysiologically relevant
      clinical settings, with a proof of concept for the beneficial effect of ROS
      suppressors.

PMID- 22362363
TI  - Flower-deficient mice have reduced susceptibility to skin papilloma formation.
AB  - Skin papillomas arise as a result of clonal expansion of mutant cells. It has
      been proposed that the expansion of pretumoral cell clones is propelled not only
      by the increased proliferation capacity of mutant cells, but also by active cell
      selection. Previous studies in Drosophila describe a clonal selection process
      mediated by the Flower (Fwe) protein, whereby cells that express certain Fwe
      isoforms are recognized and forced to undergo apoptosis. It was further shown
      that knock down of fwe expression in Drosophila can prevent the clonal expansion
      of dMyc-overexpressing pretumoral cells. Here, we study the function of the
      single predicted mouse homolog of Drosophila Fwe, referred to as mFwe, by clonal
      overexpression of mFwe isoforms in Drosophila and by analyzing mFwe knock-out
      mice. We show that clonal overexpression of certain mFwe isoforms in Drosophila
      also triggers non-autonomous cell death, suggesting that Fwe function is
      evolutionarily conserved. Although mFwe-deficient mice display a normal
      phenotype, they develop a significantly lower number of skin papillomas upon
      exposure to DMBA/TPA two-stage skin carcinogenesis than do treated wild-type and
      mFwe heterozygous mice. Furthermore, mFwe expression is higher in papillomas and
      the papilloma-surrounding skin of treated wild-type mice compared with the skin
      of untreated wild-type mice. Thus, we propose that skin papilloma cells take
      advantage of mFwe activity to facilitate their clonal expansion.

PMID- 22362364
TI  - Anaplasma phagocytophilum seroprevalence in equids: a survey in Sicily (Italy).
AB  - This study was undertaken to determine the prevalence of Anaplasma
      phagocytophilum infection in Equidae and investigate the possibility of exposure
      to the organism in Sicily (Southern Italy). During the study blood samples were
      collected in horses and donkeys housed in five of the nine provinces of Sicilian
      Island. Of 133 horses and 100 donkeys tested, respectively 9.0% and 6.0% were
      seroactive (IFAT) with A. phagocytophilum antigen. In only 4.7% of the horses,
      specific A. phagocytophilum DNA was recorded; in donkey, Anaplasma DNA was not
      found. Our results indicate a low prevalence of A. phagocytophilum in Sicilian
      equids. This condition does not justify the exclusion of equids from prophylactic
      plans for this multihost pathogen infection, a zoonosis with a wide distribution
      in other European countries. However, further studies are necessary to elucidate
      the possible mechanisms that involve the Equidae as host of this pathogen.

PMID- 22362366
TI  - Striking similarities between pallidotomy and STN DBS at very long-term follow
      up.

PMID- 22362365
TI  - Development of metronidazole-resistant lines of Blastocystis sp.
AB  - Metronidazole (MTR) is frequently used for the treatment of Blastocystis
      infections, but with variable effectiveness, and often with treatment failures as
      a possible result of drug resistance. We have developed two Blastocystis MTR
      resistant (MTR(R)) subtype 4 WR1 lines (WR1-M4 and WR1-M5), with variable
      susceptibility to a panel of anti-protozoal agents including various 5
      nitroimidazoles, nitazoxanide and furazolidone. WR1-M4 and WR1-M5 were developed
      and assessed over an 18-month period and displayed persistent MTR resistance,
      being more than 2.5-fold less susceptible to MTR than the parent isolate. The
      MTR(R) lines grew with a similar g time to WR1, but were morphologically less
      consistent with a mixture of size. All Blastocystis isolates and the MTR(R) lines
      were most susceptible to the 5-nitroimidazole drug ronidazole. WR1-M5 was
      apparently cross-resistant to satranidazole and furazolidone, and WR1-M4 was
      cross-resistant to nitazoxanide. These MTR(R) lines now provide a valuable tool
      for the continued assessment of the efficacy and mechanism of action of new and
      established drugs against a range of Blastocystis sp. subtypes, in order to
      identify a universally effective drug and to facilitate understanding of the
      mechanisms of drug action and resistance in Blastocystis.

PMID- 22362367
TI  - Recipient and donor body mass index as important risk factors for delayed kidney
      graft function.
AB  - BACKGROUND: Obesity is increasingly impacting the overall health status and the
      global costs for health care. The increase in body mass index (BMI) is also
      observed in kidney allograft recipients and deceased organ donors. METHODS: In a
      retrospective single-center study, we analyzed 1132 deceased donor kidney grafts,
      transplanted at our institution between 2000 and 2009 for recipient and donor BMI
      and its correlation with delayed graft function (DGF). Recipients/donors were
      classified according to their BMI (<18.5, 18.5-24.9, 25-29.9, and >30 kg/m(2)).
      DGF was defined as requirement for one dialysis within the first week after
      transplantation. RESULTS: Overall DGF rate was 32.4%, mean recipient BMI was
      23.64 +/- 3.75 kg/m(2), and mean donor BMI was 24.69 +/- 3.44 kg/m(2). DGF rate
      was 25.2%, 29.8%, 40.9%, and 52.6% in recipients with BMI less than 18.5, 18.5 to
      24.9, 25 to 29.9, and more than 30 kg/m, respectively (P<0.0001). Donor BMI less
      than 18.5, 18.5 to 24.9, 25 to 29.9, more than 30 kg/m(2) resulted in a DGF rate
      of 22.5%, 31.0%, 37.3%, and 51.2% (P < 0.0001). Multivariate analysis revealed
      recipient BMI and dialysis duration as independent risk factors for DGF. DGF
      results in inferior 1- and 5-year graft and patient survival. CONCLUSION:
      Recipient and donor BMI correlate with the incidence of DGF. Awareness thereof
      should have an impact on peri- and posttransplant measures in renal transplant
      recipients.

PMID- 22362368
TI  - Review of living kidney donor guidelines is out of date before publication.

PMID- 22362370
TI  - Cognition and resective surgery for diffuse infiltrative glioma: an overview.
AB  - Compared to classical oncological outcome measures such as time to progression
      and survival, the importance of cognitive functioning in patients with diffuse
      infiltrative brain tumors has only recently been recognized. Apart from the
      relatively low incidence and the invariably fatal outcome of gliomas, the general
      assumption that cognitive assessment is time-consuming and burdensome contributes
      to this notion. Our understanding of the effects of brain surgery on cognition,
      for instance, is largely based on studies in surgical patients with refractory
      epilepsy, with only a limited number of studies in surgical patients with
      gliomas. The impact of other factors affecting cognition in glioma patients such
      as direct tumor effects, radiotherapy and chemotherapy, and medical treatment,
      including anti-epileptic drugs and steroids, have been studied more extensively.
      The purpose of this paper is to provide an overview of cognition in patients with
      diffuse infiltrative gliomas and the impact of resective surgery as well as other
      tumor and treatment-related factors.

PMID- 22362371
TI  - Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade
      gliomas (LGG).
AB  - We describe how a neuropsychological evaluation in patients with brain tumors
      should be performed, specifically in the case of low-grade gliomas.
      Neuropsychological examination is crucial before starting any treatment as well
      as during the follow-up, since it can improve neurosurgery techniques and reveal
      potential cognitive effects of chemotherapy and radiotherapy, besides planning
      rehabilitation. We underline that sensitive and wide-ranging tests are required;
      specific tasks based on the lesion site should be added. Moreover, some tests can
      provide additional information about the evolution of the tumor. A careful,
      thorough examination improves quality of life.

PMID- 22362372
TI  - Recent advances and updated guidelines in the management of chemotherapy-induced 
      nausea and vomiting.
AB  - One of the most dreaded side effects of anticancer treatment, chemotherapy
      induced nausea and vomiting (CINV) plays a significant role in cancer patients'
      morbidity and quality of life. The management of CINV has been refined over the
      past several decades, and CINV can now be addressed with targeted prophylactic
      medications aimed at inhibiting the molecular pathways involved in emesis,
      including serotonin receptor antagonists and neurokinin-1 receptor antagonists.
      Advances in the understanding of the physiology of CINV, coupled with the
      introduction of several agents that inhibit activation of these receptors, are
      reflected in current CINV guidelines. These guidelines, which are largely
      similar, provide recommendations based on expert review of available clinical
      trial data. Despite the availability of effective prophylaxis, many patients
      still suffer from CINV. To minimize these side effects, clinicians should ensure
      widespread adoption and implementation of at least 1 CINV guideline in their
      practice. Even when the recommendations are followed, a small group of patients
      continue to experience CINV, often in the form of nausea, for which few
      treatments are effective. Current and future studies will begin to delineate the
      specific pathways for the development of nausea, hopefully leading to the
      identification of novel agents and regimens with improved efficacy in this
      setting.

PMID- 22362373
TI  - Obtaining outcome data on asthma  management: the UK National Review of  Asthma
      Deaths.

PMID- 22362374
TI  - Optimal allocation of participants for the estimation of selection, preference
      and treatment effects in the two-stage randomised trial design.
AB  - Outcomes in clinical trials may be affected by the choice of treatment that
      participants might make, if they were indeed allowed to choose (a so-called
      selection effect), and by whether they actually receive their preferred treatment
      (a preference effect). Selection and preference effects can be important, but
      they cannot be estimated in the conventional trial design. An alternative
      approach is the two-stage randomised trial, in which participants are first
      randomly divided into two subgroups. In one subgroup, participants are randomly
      assigned to treatments, while in the other, participants are allowed to choose
      their own treatment. This approach yields estimates of the direct treatment
      effect, and of the preference and selection effects. The latter two provide
      insight that goes considerably beyond what is possible in the standard randomised
      trial. In this paper, we determine the optimal proportion of participants who
      should be allocated to the choice subgroup. The precision of the estimated
      selection, preference and treatment effects are functions of: the total sample
      size; the proportion of participants allocated to choose their treatment; the
      variances of the outcome; the proportions of participants who select each
      treatment in the choice group; and the selection, preference and treatment
      effects themselves. We develop general expressions for the optimum proportion of
      participants in the choice group, depending on which effects are of primary
      interest. We illustrate the results with trial data comparing alternative
      clinical management strategies for women with abnormal results on cervical
      screening.

PMID- 22362375
TI  - Heterocyclic dithiocarbazate iron chelators: Fe coordination chemistry and
      biological activity.
AB  - The iron coordination and biological chemistry of a series of heterocyclic
      dithiocarbazate Schiff base ligands is reported with regard to their activity as
      Fe chelators for the treatment of Fe overload and also cancer. The ligands are
      analogous to tridentate heterocyclic hydrazone and thiosemicarbazone chelators we
      have studied previously which bear NNO and NNS donor sets. The dithiocarbazate
      Schiff base ligands in this work also are NNS chelators and form stable low spin
      ferric and ferrous complexes and both have been isolated. In addition an unusual
      hydroxylated ligand derivative has been identified via an Fe-induced oxidation
      reaction. X-ray crystallographic and spectroscopic characterisation of these
      complexes has been carried out and also the electrochemical properties have been
      investigated. All Fe complexes exhibit totally reversible Fe(III/II) couples in
      mixed aqueous solvents at potentials higher than found in analogous
      thiosemicarbazone Fe complexes. The ability of the dithiocarbazate Schiff base
      ligands to mobilise Fe from cells and also to prevent Fe uptake from transferrin
      was examined and all ligands were effective in chelating intracellular Fe
      relative to known controls such as the clinically important Fe chelator
      desferrioxamine. The Schiff base ligands derived from 2-pyridinecarbaldehyde were
      non-toxic to SK-N-MC neuroepithelioma (cancer) cells but those derived from the
      ketones 2-acetylpyridine and di-2-pyridyl ketone exhibited significant
      antiproliferative activity.

PMID- 22362377
TI  - Expression profile analysis of the polygalacturonase-inhibiting protein genes in
      rice and their responses to phytohormones and fungal infection.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are typically leucine-rich repeat
      (LRR) proteins that can inhibit the activity of fungal polygalacturonases (PGs).
      In this study, two new Ospgip genes, named Ospgip6 and Ospgip7 with consensus
      sequence of ten imperfect LRR motif located on rice chromosomes 8 and 9, were
      identified using BLAST analysis. Both of them appear to be extracellular
      glycoproteins. To have a global view of the dynamic gene expression pattern,
      seven Ospgip genes were first analyzed using the Affymetrix rice genome array
      data from online resource. All of these seven Ospgip genes showed variable
      expression patterns among tissues/organs. In order to further investigate the
      potential function of these Ospgip genes, the responses of Ospgip genes to the
      treatment of various phytohormones (abscisic acid, brassinosteroid, gibberellic
      acid, 3-indole acetic acid, jasmonic acid, kinetin, naphthalene acetic acid and
      salicylic acid) as well as fungal infection were analyzed by real-time PCR using
      time course array. Generally, all the Ospgip genes were slightly up-regulated in
      the indica rice cultivar Minghui 63 under GA(3), KT and NAA treatments (except
      Ospgip2, which was down-regulated under KT treatment). In the japonica rice
      cultivar Zhonghua 11, Ospgip genes were regulated by most treatments with the
      response time variability. We also analyzed putative cis-elements in the promoter
      regions of Ospgip genes. This dataset provided a versatile resource to understand
      the regulatory network of Ospgip genes during the process of phytohormones
      treatment and fungal infection in the model monocotyledonous plant, rice, and
      could aid in the transgenic breeding against rice fungal diseases. KEY MESSAGE:
      All the seven Ospgip genes showed variable expression patterns in Minghui 63 and
      their expressions were regulated by different phytohormone treatments or fungal
      infection in Minghui 63 and Zhonghua 11.

PMID- 22362376
TI  - Fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric
      cancer with peritoneal metastasis.
AB  - BACKGROUND: There are few data on the efficacy of combination chemotherapy with a
      fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric
      cancer (AGC) complicated by peritoneal metastasis, especially massive ascites.
      METHODS: We retrospectively evaluated the efficacy and safety of a
      fluoropyrimidine (S-1 or capecitabine) plus cisplatin as first-line chemotherapy
      in 120 patients with AGC and peritoneal metastasis. RESULTS: Ascites was detected
      in 50 patients, with 11 patients having massive ascites. Median progression-free
      survival (PFS) and overall survival (OS) of all patients was 6.1 and 15.9 months,
      respectively. The PFS and OS were shorter in patients with massive ascites (n =
      11; 3.7 and 9.5 months) compared with patients with small or moderate ascites (n
      = 39; 5.8 and 13.5 months) or patients without ascites (n = 70; 6.9 and 18.1
      months). The objective response in terms of ascites was similar whether ascites
      was massive (4 of 11 patients; 36.4%) or small or moderate (16 of 39 patients;
      41%). The frequencies of grade 3 or higher toxicity or treatment discontinuation
      due to toxicity are relatively similar across ascites groups. CONCLUSIONS:
      Fluoropyrimidine plus cisplatin appears to be tolerated in selected patients with
      peritoneal metastasis.

PMID- 22362378
TI  - The development and validation of the Body Image Dimensional Assessment (BIDA).
AB  - AIM: To validate a silhouette-based scale, the Body Image Dimensional Assessment
      (BIDA), an instrument for the screening of body dissatisfaction in large samples.
      MATERIALS AND METHODS: Five-hundred ninety-two both gender non-clinical
      participants and 57 patients with eating disorders (ED) were administered the
      BIDA and the Body Dissatisfaction subscale of the Eating Disorder Inventory 2 (BD
      EDI2). The BIDA consists of only 4 items to answer with reference to a series of
      four silhouettes not age- nor gender-related using a numeric scale that allows
      the quantification of the degree of Body Dissatisfaction, Sexual Body
      Dissatisfaction, Comparative Body Dissatisfaction and the calculation of the
      final Body Dissatisfaction Index (BDI). RESULTS AND CONCLUSIONS: The study has
      shown that the BIDA has good reliability and validity as well as high predictive
      capability at a threshold BDI>=30 (sensitivity = 83.3% and specificity = 92.1%).
      By virtue of the rapid timing of administration, the BIDA can be a useful
      screening instrument of body dissatisfaction in non clinical populations to
      detect people at risk for ED and a follow-up instrument in clinical setting.

PMID- 22362379
TI  - Dioxindole in asymmetric catalytic synthesis: direct access to 3-substituted 3
      hydroxy-2-oxindoles via 1,4-additions to nitroalkenes.
AB  - The asymmetric Michael addition of dioxindoles to beta-substituted nitroalkenes
      is reported. The bifunctional primary amine-thiourea A, by means of a non
      covalent-based mode of catalysis, secures direct access to 3-substituted 3
      hydroxyoxindole derivatives with high stereocontrol.

PMID- 22362380
TI  - Application of low-level laser therapy for noninvasive body contouring.
AB  - BACKGROUND: Low-level laser therapy (LLLT) is a noninvasive treatment for a wide
      assortment of medical ailments. A recent application is for noninvasive body
      slimming. A Level 1 clinical study was completed and recorded a significant
      reduction in circumferential measurements across waist, hips, and thighs compared
      to placebo subjects. Questions remain unanswered to whether the result observed
      was based upon simple fluid redistribution. The purpose of this retrospective
      study was to evaluate the efficacy of LLLT for noninvasive body slimming and
      determine if the loss was attributable to fluid or fat relocation. METHODS: Data
      from 689 participants were obtained to evaluate the circumferential reduction
      demonstrated across the treatment site of the waist, hips, and thighs as well as
      nontreated systemic regions. Patient data were not pre-selected; all reports
      provided by clinics using LLLT for body contouring were used to evaluate the
      efficacy of this treatment. Participants received a total of six LLLT treatments
      across 2-weeks having baseline and post-procedure circumferential measurements
      recorded. Measurement sites included waist, hips, thighs, arms, knees, neck, and
      chest. RESULTS: The mean circumferential reduction reported for the waist, hips,
      and thighs 1 week after the treatment regimen was 3.27 in. (P < 0.0001).
      Furthermore, participants demonstrated an overall mean reduction of 5.17 in.
      across all measurement points 5.17 in. (P < 0.0001). Each anatomical region
      measured exhibited a significant circumferential reduction. CONCLUSION: These
      data reveal that the circumferential reduction exhibited following LLLT is not
      attributable to fluid or fat relocation as all measurement points, including
      nontreated regions, reported an inch loss.

PMID- 22362381
TI  - The epigenetic silencing of the estrogen receptor (ER) by hypermethylation of the
      ESR1 promoter is seen predominantly in triple-negative breast cancers in Indian
      women.
AB  - The proportion of estrogen receptor (ER)-negative and triple-negative (TN) breast
      cancer in Indian women is higher than that reported in the West, and this
      difference persists even after their migration to the West. The causes for this
      significant difference are not entirely clear. Hypermethylation of the ER
      promoter, an epigenetic alteration, is known to be one of the mechanisms by which
      the expression of ER is suppressed. Two thirds of breast cancer specimens from an
      Indian center tested, using the highly sensitive, methylation-specific polymerase
      chain reaction (MSP) technique, were reported positive. We have used a
      quantitative assay, the MethyLight, to better assess the extent of methylation in
      the ESR1 promoter region in 98 breast cancer tumor specimens from Indian women.
      In addition, the amount of ER transcripts was determined by quantitative reverse
      transcriptase polymerase chain reaction. Using the stringent cutoff of at least
      4% of the target sequence being methylated, 27% of TN tumors were methylated. In
      addition they demonstrated the highest levels of methylation. In contrast less
      than 2% ER-positive tumors were hypermethylated. While the proportion of
      hypermethylated tumors are lower in this study than that estimated using MSP, our
      results support the notion of increased epigenetic deregulations in ER-negative
      tumors in general and TN tumors in particular. The development of this assay also
      permits a rational approach to the selection of patients for clinical trials
      examining the efficacy of demethylating agents in the treatment of ER-negative
      breast cancer.

PMID- 22362382
TI  - Combination of EGFR and COX-2 inhibitors in breast cancer patient.
AB  - Ther combination of EGFR and COX-2 inhibitors in breast cancer patient treatment
      is a topic of interest. In this work, the author discusses on the synergistic
      effect of concomitant usage of the two drugs and also further notes on the myth
      in using this combination.

PMID- 22362383
TI  - Detection of DNA hypermethylation in remote media of patients with colorectal
      cancer: new biomarkers for colorectal carcinoma.
AB  - Colorectal cancer is the third most common cancer and a major cause of cancer
      related mortality. The lifetime risk to develop colorectal cancer is 6% in the
      Western world, and one third of the affected people will ultimately die from this
      disease. Colorectal carcinomas develop slowly over a period of several years.
      Therefore, identifying people with precancerous lesions holds the potential to
      reduce the incidence and mortality of colorectal cancer. Apart from mutations and
      chromosomal imbalances, inactivation of tumor suppressor genes by DNA
      hypermethylation has been recognized as an important mechanism driving colorectal
      carcinogenesis. In recent years, screening tests have been developed that rely on
      the detection of DNA hypermethylation in remote media to identify people
      suffering from asymptomatic colorectal cancers at early stages. Apart from their
      diagnostic value, methylation markers hold the potential to be used as prognostic
      markers. Here, we summarize the recent development of DNA methylation markers for
      colorectal cancer in remote media with regard to their diagnostic and prognostic
      value.

PMID- 22362386
TI  - Role of sphingomyelin synthesis in pulmonary endothelial cell cytoskeletal
      activation and endotoxin-induced lung injury.
AB  - Sphingomyelin (SM), a major sphingolipid in the lipid raft microdomains of the
      cell membrane, is synthesized by plasma membrane-bound sphingomyelin synthase 2
      (SMS2). SMS2 is required for the maintenance of plasma membrane microdomain
      fluidity and receptor-mediated responses to inflammation in macrophages. However,
      the exact mechanism of SMS2 activation in endothelial barrier disruption and lung
      injury is not fully understood. To define the role of SMS activation in lung
      injury, we hypothesized that the inhibition of SM synthesis may provide
      protection against acute lung injury (ALI) by preserving endothelial barrier
      function. Using SMS2-silencing RNA (siRNA) treatment in human pulmonary
      endothelial cells (HPAECs) and tricyclodecan-9-yl-xanthogenate (D609), a
      competitive inhibitor of SMS, and phosphatidylcholine-specific phospholipase C in
      a murine model of bacterial LPS injury, we studied the role of sphingomyelin
      synthesis in ALI. Results show that pretreating mice with D609 significantly
      attenuated LPS-induced lung injury, as measured by a significant decrease in wet
      to dry ratio, bronchoalveolar lavage fluid cell and protein counts, and
      myeloperoxidase activity in lung tissue. Similarly, LPS-induced endothelial
      barrier disruption was significantly reduced in HPAECs pretreated with D609 or
      SMS2 siRNA, as demonstrated by an increase in paracellular integrity on an FITC
      dextran assay, by the inhibition of LPS-induced stress fibers, and by the
      formation of cortical actin rings and lamellipodia at the periphery. These
      results indicate that D609 attenuates LPS-mediated endothelial barrier
      dysfunction and lung injury in mice through inhibition of SMS, suggesting a novel
      and essential role of SMS inhibition in modulating endothelial barrier integrity
      via actin cytoskeletal activation, with a potential therapeutic role in ALI.

PMID- 22362384
TI  - Nitric oxide release: part II. Therapeutic applications.
AB  - A wide range of nitric oxide (NO)-releasing materials has emerged as potential
      therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing
      scaffolds are particularly promising due to their ability to store and deliver
      larger NO payloads in a more controlled and effective manner compared to low
      molecular weight NO donors. While a variety of scaffolds (e.g., particles,
      dendrimers, and polymers/films) have been cleverly designed, the ultimate
      clinical utility of most NO-releasing macromolecules remains unrealized. Although
      not wholly predictive of clinical success, in vitro and in vivo investigations
      have enabled a preliminary evaluation of the therapeutic potential of such
      materials. In this tutorial review, we review the application of macromolecular
      NO therapies for cardiovascular disease, cancer, bacterial infections, and wound
      healing.

PMID- 22362387
TI  - mCLCA3 does not contribute to calcium-activated chloride conductance in murine
      airways.
AB  - Ca(2+)-activated Cl(-) channels (CaCCs) contribute to airway Cl(-) and fluid
      secretion, and were implicated in the modulation of disease severity and as a
      therapeutic target in cystic fibrosis (CF). Previous in vitro studies suggested
      that members of the CLCA gene family, including the murine mCLCA3, contribute to
      CaCCs. However, the role of mCLCA3 in ion transport in native airway epithelia
      has not been studied, to the best of our knowledge. In this study, we used mCLCA3
      deficient mice and determined bioelectric properties in freshly excised tracheal
      tissue, airway morphology, and gene expression studies, to determine the role of
      mCLCA3 in airway ion transport and airway structure. Bioelectric measurements did
      not detect any differences in basal short-circuit current, amiloride-sensitive
      Na(+) absorption, cyclic adenosine monophosphate-dependent Cl(-) secretion, and
      activation of Ca(2+)-activated (uridine-5'-triphosphate-mediated) Cl(-) secretion
      in mCLCA3-deficient mice compared with wild-type mice. Moreover, no histological
      changes were observed in the respiratory tract or any other tissues of mCLCA3
      deficient mice when compared with wild-type control mice. The intratracheal
      instillation of IL-13 produced an approximately 30-fold up-regulation of mCLCA3
      transcripts without inducing CaCC activity in wild-type airways, and induced
      goblet-cell hyperplasia and mucin gene expression to similar levels in both
      genotypes. Further, multiple specific reverse-transcriptase quantitative PCR
      assays for other CaCC candidates, including mCLCA1, mCLCA2, mCLCA4, mCLCA5,
      mCLCA6, mCLCA7, mBEST1, mBEST2, mCLC4, mTTYH3, and mTMEM16A, failed to identify
      the differential expression of genes in the respiratory tract that may compensate
      for a lack of mCLCA3 function. Together, these findings argue against a role of
      mCLCA3 in CaCC-mediated Cl(-) secretion in murine respiratory epithelia.

PMID- 22362385
TI  - Role of CXCL5 in leukocyte recruitment to the lungs during secondhand smoke
      exposure.
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of
      mortality in the United States. The major cause of COPD is cigarette smoking.
      Extensive leukocyte influx into the lungs, mediated by chemokines, is a critical
      event leading to COPD. Although both resident and myeloid cells secrete
      chemokines in response to inflammatory stimuli, little is known about the role of
      epithelial-derived chemokines, such as CXC chemokine ligand (CXCL)5, in the
      pathogenesis of cigarette smoke-induced inflammation. To explore the role of
      CXCL5, we generated CXCL5 gene-deficient mice and exposed them to secondhand
      smoke (SHS) for 5 hours/day for 5 days/week up to 3 weeks (subacute exposure). We
      observed a reduced recruitment of leukocytes to the lungs of CXCL5(-/-) mice
      compared with their wild-type (WT) counterparts, and noted that macrophages
      comprised the predominant leukocytes recruited to the lungs. Irradiation
      experiments performed on CXCL5(-/-) or WT mice transplanted with WT or CXCL5(-/-)
      bone marrow revealed that resident but not hematopoietic cell-driven CXCL5 is
      important for mediating SHS-induced lung inflammation. Interestingly, we observed
      a significant reduction of monocyte chemotactic protein-1 (MCP-1/CC chemokine
      ligand 2) concentrations in the lungs of CXCL5(-/-) mice. The instillation of
      recombinant MCP-1 in CXCL5(-/-) mice reversed macrophage recruitment. Our results
      also show the reduced activation of NF-kappaB/p65 in the lungs, as well as the
      attenuated activation of C-Jun N-terminal kinase, p42/44, and p38 mitogen
      activated protein kinases and the expression of intercellular adhesion molecule-1
      in the lungs of SHS-exposed CXCL5(-/-) mice. Our findings suggest an important
      role for CXCL5 in augmenting leukocyte recruitment in SHS-induced lung
      inflammation, and provide novel insights into CXCL5-driven pathogenesis.

PMID- 22362388
TI  - Caveolin-1 deficiency protects from pulmonary fibrosis by modulating epithelial
      cell senescence in mice.
AB  - Idiopathic pulmonary fibrosis is associated with a decreased expression of
      caveolin-1 (cav-1), yet its role remains unclear. To investigate the role of cav
      1, we induced pulmonary fibrosis in wild-type (WT) and cav-1-deficient (cav-1(-/
      )) mice using intratracheal instillation of bleomycin. Contrary to expectations,
      significantly less collagen deposition was measured in tissue from cav-1(-/-)
      mice than in their WT counterparts, consistent with reduced mRNA expression of
      procollagen1a2 and procollagen3a1. Moreover, cav-1(-/-) mice demonstrated 77%
      less alpha-smooth muscle actin staining, suggesting reduced mesenchymal cell
      activation. Levels of pulmonary injury, assessed by tenascin-C mRNA expression
      and CD44v10 detection, were significantly increased at Day 21 after injury in WT
      mice, an effect significantly attenuated in cav-1(-/-) mice. The apparent
      protective effect against bleomycin-induced fibrosis in cav-1(-/-) mice was
      attributed to reduce cellular senescence and apoptosis in cav-1(-/-) epithelial
      cells during the early phase of lung injury. Reduced matrix metalloproteinase
      (MMP)-2 and MMP-9 expressions indicated a low profile of senescence-associated
      secretory phenotype (SASP) in the bleomycin-injured cav-1(-/-) mice. However, IL
      6 and macrophage inflammatory protein 2 were increased in WT and cav-1(-/-) mice
      after bleomycin challenge, suggesting that bleomycin-induced inflammatory
      response substantiated the SASP pool. Thus, loss of cav-1 attenuates early injury
      response to bleomycin by limiting stress-induced cellular senescence/apoptosis in
      epithelial cells. In contrast, decreased cav-1 expression promotes fibroblast
      activation and collagen deposition, effects that may be relevant in later stages
      of reparative response. Hence, therapeutic strategies to modulate the expression
      of cav-1 should take into account cell-specific effects in the regenerative
      responses of the lung epithelium to injury.

PMID- 22362390
TI  - Cell type-specific postsynaptic effects of neuropeptide Y in substantia
      gelatinosa neurons of the rat spinal cord.
AB  - Cellular mechanisms of antinociceptive action of neuropeptide Y were investigated
      in substantia gelatinosa (SG) neurons in rat spinal cord slices. Somatic and
      synaptic effects of NPY were compared in two subpopulations of cells with
      different firing patterns, tonic (TFNs), and delayed firing (DFNs) neurons. For
      the study, TFNs were selected on morphological basis: they had appearance of
      central and radial but not islet cells, and are likely excitatory interneurons in
      dorsal horn networks. In their turn, DFNs were classified as radial and vertical
      cells. 0.3 MUM NPY via Y1 receptors activated hyperpolarizing postsynaptic
      current of GIRK type in majority of TFNs (~77%) but not DFNs (~8%). Miniature
      synaptic currents in all neurons were seen as a mixture of excitatory (mEPSCs)
      and inhibitory (mIPSCs), the frequency of the former being ~5 times greater. The
      mEPSCs were mediated by glutamate receptors of AMPA subtype, while the dominant
      part of mIPSCs--by glycine receptors. In all cell types, NPY moderately depressed
      the frequency of both mEPSCs and mIPSCs; the effects occurred via Y2 and Y1
      receptors, respectively. The data suggest that behavioral NPY-evoked
      antinociception is achieved via postsynaptic hyperpolarization of majority of
      TFNs (assumingly, excitatory interneurons) via Y1 receptors and depression of the
      mEPSCs via Y2 receptors.

PMID- 22362391
TI  - Prognostic role of methylated free circulating DNA in colorectal cancer.
AB  - DNA hypermethylation is frequently found in colorectal cancer (CRC). Methylation
      of helicase-like transcription factor (HLTF) and hyperplastic polyposis 1 (HPP1)
      are potential and carcinoembryonic antigen (CEA) is an established prognostic
      factor in serum of patients with CRC. The aim of this study was to perform a
      direct comparison of the prognostic roles of these markers. Methylation status of
      HLTF and HPP1 was examined in pretherapeutic sera of 311 patients with CRC and
      matched primary tissues of 54 stage IV patients using methylation-specific
      quantitative PCR. CEA was determined using an immunoenzymometric assay.
      Methylation of HLTF and HPP1 DNA in serum significantly correlated with tumor
      size, stage, grade and metastatic disease. HPP1 methylation correlated with nodal
      status. Overall survival was shortened in case of methylation of HLTF or HPP1 or
      elevated levels of CEA (p < 0.0001 for all). In stage IV, patients survival was
      impaired if HLTF (p = 0.0005) or HPP1 (p = 0.0003) were methylated or CEA was
      above the median of 27 ng/ml (p = 0.002). Multivariate analysis revealed that
      methylation of HLTF [hazard ratio (HR) 1.8, p = 0.0438], HPP1 (HR 1.6, p =
      0.0495) and CEA >27 ng/ml (HR 1.7, p = 0.0317) were independent prognostic
      factors in stage IV. The combination of any two or all three of these factors
      outperformed each marker on its own. In conclusion, the presence of methylated
      DNA of the genes HLTF or HPP1 in serum are independent prognostic factors in
      metastasized CRC. Prospective validation is required to determine their
      usefulness in clinical routine along with the established marker CEA.

PMID- 22362392
TI  - Neuroprotective effects of statins: evidence from preclinical and clinical
      studies.
AB  - OPINION STATEMENT: The benefits of statins for both primary and secondary
      prevention of ischemic stroke are clearly established. Evidence is accumulating
      that statin withdrawal after ischemic stroke may lead to worse outcome and that
      initiation of statins after ischemic stroke may reduce mortality and improve
      outcome. Current treatment guidelines recommend starting statins before discharge
      in patients with stroke related to atherosclerosis or who have elevated
      cholesterol. The primary treatment question then is not if to start statins in
      most ischemic stroke patients, but when. Our recommendation would be start a
      statin as soon as the patient passes a dysphagia screen and can safely take oral
      medication. Based on the results of the Heart Protection Study and the SPARCL
      trial, either simvastatin 40 mg or atorvastatin 80 mg are appropriate
      alternatives. Clinical trials are needed to demonstrate unequivocal efficacy of
      improved outcome and to determine if lower doses may have this effect.
      Additionally, improved outcome needs to be established in cardioembolic stroke
      patients before routine use of statins in this stroke subtype can be recommended.

PMID- 22362394
TI  - Auditory emotion recognition impairments in schizophrenia: relationship to
      acoustic features and cognition.
AB  - OBJECTIVE: Schizophrenia is associated with deficits in the ability to perceive
      emotion based on tone of voice. The basis for this deficit remains unclear,
      however, and relevant assessment batteries remain limited. The authors evaluated
      performance in schizophrenia on a novel voice emotion recognition battery with
      well-characterized physical features, relative to impairments in more general
      emotional and cognitive functioning. METHOD: The authors studied a primary sample
      of 92 patients and 73 comparison subjects. Stimuli were characterized according
      to both intended emotion and acoustic features (e.g., pitch, intensity) that
      contributed to the emotional percept. Parallel measures of visual emotion
      recognition, pitch perception, general cognition, and overall outcome were
      obtained. More limited measures were obtained in an independent replication
      sample of 36 patients, 31 age-matched comparison subjects, and 188 general
      comparison subjects. RESULTS: Patients showed statistically significant large
      effect-size deficits in voice emotion recognition (d=1.1) and were preferentially
      impaired in recognition of emotion based on pitch features but not intensity
      features. Emotion recognition deficits were significantly correlated with pitch
      perception impairments both across (r=0.56) and within (r=0.47) groups. Path
      analysis showed both sensory-specific and general cognitive contributions to
      auditory emotion recognition deficits in schizophrenia. Similar patterns of
      results were observed in the replication sample. CONCLUSIONS: The results
      demonstrate that patients with schizophrenia show a significant deficit in the
      ability to recognize emotion based on tone of voice and that this deficit is
      related to impairment in detecting the underlying acoustic features, such as
      change in pitch, required for auditory emotion recognition. This study provides
      tools for, and highlights the need for, greater attention to physical features of
      stimuli used in studying social cognition in neuropsychiatric disorders.

PMID- 22362395
TI  - Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.
AB  - OBJECTIVE: Many studies have shown that 5-HTTLPR genotype interacts with exposure
      to stress in conferring risk for psychopathology. However, the specific neural
      mechanisms through which this gene-by-environment interaction confers risk remain
      largely unknown, and no study to date has directly examined the modulatory
      effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute
      stress. METHOD: An acute laboratory stressor was administered to 51 healthy women
      during blood-oxygen-level-dependent functional magnetic resonance imaging. In
      this task, participants were threatened with electric shocks of uncertain
      intensity, which were unpredictably delivered to the wrist after a long
      anticipatory cue period of unpredictable duration. RESULTS: Relative to women
      carrying the L allele, those with the SS genotype showed enhanced activation
      during threat anticipation in a network of regions, including the amygdala,
      hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior
      cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype
      also displayed enhanced positive coupling between medial prefrontal cortex
      activation and anxiety experience, whereas enhanced negative coupling between
      insula activation and perceived success at regulating anxiety was observed in
      individuals carrying the L allele. CONCLUSIONS: These findings suggest that
      during stress exposure, neural systems that enhance fear and arousal, modulate
      attention toward threat, and perseverate on emotional salience of the threat may
      be engaged preferentially in individuals with the SS genotype. This may be one
      mechanism underlying the risk for psychopathology conferred by the S allele upon
      exposure to life stressors.

PMID- 22362397
TI  - Differences in white matter fiber tract development present from 6 to 24 months
      in infants with autism.
AB  - OBJECTIVE: Evidence from prospective studies of high-risk infants suggests that
      early symptoms of autism usually emerge late in the first or early in the second
      year of life after a period of relatively typical development. The authors
      prospectively examined white matter fiber tract organization from 6 to 24 months
      in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.
      METHOD: The participants were 92 high-risk infant siblings from an ongoing
      imaging study of autism. All participants had diffusion tensor imaging at 6
      months and behavioral assessments at 24 months; a majority contributed additional
      imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for
      ASDs and 64 infants did not. Microstructural properties of white matter fiber
      tracts reported to be associated with ASDs or related behaviors were
      characterized by fractional anisotropy and radial and axial diffusivity. RESULTS:
      The fractional anisotropy trajectories for 12 of 15 fiber tracts differed
      significantly between the infants who developed ASDs and those who did not.
      Development for most fiber tracts in the infants with ASDs was characterized by
      higher fractional anisotropy values at 6 months followed by slower change over
      time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs
      had lower values. CONCLUSIONS: These results suggest that aberrant development of
      white matter pathways may precede the manifestation of autistic symptoms in the
      first year of life. Longitudinal data are critical to characterizing the dynamic
      age-related brain and behavior changes underlying this neurodevelopmental
      disorder.

PMID- 22362400
TI  - Research in athletes with sickle cell trait: just do it.

PMID- 22362399
TI  - Trans-spinal direct current enhances corticospinal output and stimulation-evoked
      release of glutamate analog, D-2,3-3H-aspartic acid.
AB  - Trans-spinal direct current (tsDC) stimulation is a modulator of spinal
      excitability and can influence cortically elicited muscle contraction in a
      polarity-dependent fashion. When combined with low-frequency repetitive cortical
      stimulation, cathodal tsDC [tsDC(-)] produces a long-term facilitation of
      cortically elicited muscle actions. We investigated the ability of this combined
      stimulation paradigm to facilitate cortically elicited muscle actions in spinal
      cord-injured and noninjured animals. The effect of tsDC-applied alone or in
      combination with repetitive spinal stimulation (rSS) on the release of the
      glutamate analog, D-2,3-(3)H-aspartate (D-Asp), from spinal cord preparations in
      vitro-was also tested. In noninjured animals, tsDC (-2 mA) reproducibly
      potentiated cortically elicited contractions of contralateral and ipsilateral
      muscles tested at various levels of baseline muscle contraction forces.
      Cortically elicited muscle responses in animals with contusive and hemisectioned
      spinal cord injuries (SCIs) were similarly potentiated. The combined paradigm of
      stimulation caused long-lasting potentiation of cortically elicited bilateral
      muscle contraction in injured and noninjured animals. Additional analysis
      suggests that at higher baseline forces, tsDC(-) application does not increase
      the rising slope of the muscle contraction but causes repeated firing of the same
      motor units. Both cathodal and anodal stimulations induced a significant increase
      of D-Asp release in vitro. The effect of the combined paradigm of stimulation
      (tsDC and rSS) on the concentration of extracellular D-Asp was polarity
      dependent. These results indicate that tsDC can powerfully modulate the
      responsiveness of spinal cord neurons. The results obtained from the in vitro
      preparation suggest that the changes in neuronal excitability were correlated
      with an increased concentration of extracellular glutamate. The combined paradigm
      of stimulation, used in our experiments, could be noninvasively applied to
      restore motor control in humans with SCI.

PMID- 22362398
TI  - Intermittent pneumatic leg compressions enhance muscle performance and blood flow
      in a model of peripheral arterial insufficiency.
AB  - Despite the escalating prevalence in the aging population, few therapeutic
      options exist to treat patients with peripheral arterial disease. Application of
      intermittent pneumatic leg compressions (IPC) is regarded as a promising
      noninvasive approach to treat this condition, but the clinical efficacy, as well
      the mechanistic basis of action of this therapy, remain poorly defined. We tested
      the hypothesis that 2 wk of daily application of IPC enhances exercise tolerance
      by improving blood flow and promoting angiogenesis in skeletal muscle in a model
      of peripheral arterial insufficiency. Male Sprague-Dawley rats were subjected to
      bilateral ligation of the femoral artery and randomly allocated to treatment or
      sham groups. Animals were anesthetized daily and exposed to 1-h sessions of
      bilateral IPC or sham treatment for 14-16 consecutive days. A third group of
      nonligated rats was also studied. Marked increases in treadmill exercise
      tolerance (~33%, P < 0.05) and improved muscle performance in situ (~10%, P <
      0.05) were observed in IPC-treated animals. Compared with sham-treated controls,
      blood flow measured with isotope-labeled microspheres during in situ contractions
      tended to be higher in IPC-treated animals in muscles composed of predominantly
      fast-twitch white fibers, such as the plantaris (~93%, P = 0.02). Capillary
      contacts per fiber and citrate synthase activity were not significantly altered
      by IPC treatment. Collectively, these data indicate that IPC improves exercise
      tolerance in a model of peripheral arterial insufficiency in part by enhancing
      blood flow to collateral-dependent tissues.

PMID- 22362403
TI  - Nitroso-redox balance in control of coronary vasomotor tone.
AB  - Reactive oxygen species (ROS) are essential in vascular homeostasis but may
      contribute to vascular dysfunction when excessively produced. Superoxide anion
      (O(2)(.-)) can directly affect vascular tone by reacting with K(+) channels and
      indirectly by reacting with nitric oxide (NO), thereby scavenging NO and causing
      nitroso-redox imbalance. After myocardial infarction (MI), oxidative stress
      increases, favoring the imbalance and resulting in coronary vasoconstriction.
      Consequently, we hypothesized that ROS scavenging results in coronary
      vasodilation, particularly after MI, and is enhanced after inhibition of NO
      production. Chronically instrumented swine were studied at rest and during
      exercise before and after scavenging of ROS with N-(2-mercaptoproprionyl)-glycine
      (MPG, 20 mg/kg iv) in the presence or absence of prior inhibition of endothelial
      NO synthase (eNOS) with N(omega)-nitro-L-arginine (L-NNA, 20 mg/kg iv). In normal
      swine, MPG resulted in coronary vasodilation as evidenced by an increased
      coronary venous O(2) tension, and trends toward increased coronary venous O(2)
      saturation and decreased myocardial O(2) extraction. These effects were not
      altered by prior inhibition of eNOS. In MI swine, MPG showed a significant
      vasodilator effect, which surprisingly was abolished by prior inhibition of eNOS.
      Moreover, eNOS dimer/monomer ratio was decreased after MI, reflecting eNOS
      uncoupling. In conclusion, ROS exert a small coronary vasoconstrictor influence
      in normal swine, which does not involve scavenging of NO. This vasoconstrictor
      influence of ROS is slightly enhanced after MI. Since inhibition of eNOS
      abolished rather than augmented the vasoconstrictor influence of ROS in swine
      with MI, while eNOS dimer/monomer ratio was decreased, our data imply that
      uncoupled eNOS may be a significant source of O(2)(.-) after MI.

PMID- 22362401
TI  - Reactive hyperemia is not responsible for stimulating muscle protein synthesis
      following blood flow restriction exercise.
AB  - Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity
      resistance exercise training increases muscle strength and size in humans.
      However, the mechanism(s) underlying these effects are largely unknown. We have
      previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling
      and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR
      exercise. The purpose of this study was to test the hypothesis that reactive
      hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS
      following BFR exercise. Six young men (24 +/- 2 yr) were used in a randomized
      crossover study consisting of two exercise trials: low-intensity resistance
      exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium
      nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral
      artery immediately after exercise to simulate the reactive hyperemia response
      after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic
      rate from the vastus lateralis increased by 49% in the BFR trial (P < 0.05) with
      no change in the SNP trial (P > 0.05). BFR exercise increased the phosphorylation
      of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1
      (P < 0.05) with no changes in mTORC1 signaling in the SNP trial (P > 0.05). We
      conclude that reactive hyperemia is not a primary mechanism for BFR exercise
      induced mTORC1 signaling and MPS. Further research is necessary to elucidate the
      cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and
      hypertrophy following acute and chronic BFR exercise.

PMID- 22362404
TI  - Hemodynamics and brain blood flow during posture change in younger women and
      postmenopausal women compared with age-matched men.
AB  - Increased incidence of orthostatic hypotension and presyncopal symptoms in young
      women could be related to hormonal factors that might be isolated by comparing
      cardiovascular and cerebrovascular responses to postural change in young and
      older men and women. Seven young women, 11 young men, 10 older women (>1 yr
      postmenopausal, no hormone therapy), and 9 older men participated in a supine-to
      sit-to-stand test while measuring systemic hemodynamics, end-tidal Pco(2), and
      blood flow velocity of the middle cerebral artery (MCA). Women had a greater
      reduction in stroke volume index compared with age-matched men (change from
      supine to standing: young women: -22.9 +/- 1.6 ml/m(2); young men: -14.4 +/- 2.4
      ml/m(2); older women: -17.4 +/- 3.3 ml/m(2); older men: -13.8 +/- 2.2 ml/m(2)).
      This was accompanied by offsetting changes in heart rate, particularly in young
      women, resulting in no age or sex differences in cardiac output index. Mean
      arterial pressure (MAP) was higher in older subjects and increased with movement
      to upright postures. Younger men and women had higher forearm vascular resistance
      that increased progressively in the upright posture compared with older men and
      women. There was no difference between sexes or ages in total peripheral
      resistance index. Women had higher MCA velocity, but both sexes had reduced MCA
      velocity while upright, which was a function of reduced blood pressure at the MCA
      and a significant reduction in end-tidal Pco(2). The reductions in stroke volume
      index suggested impaired venous return in women, but augmented responses of heart
      rate and forearm vascular resistance protected MAP in younger women. Overall,
      these results showed significant sex and age-related differences, but
      compensatory mechanisms preserved MAP and MCA velocity in young women.

PMID- 22362402
TI  - Sphingomyelinase depresses force and calcium sensitivity of the contractile
      apparatus in mouse diaphragm muscle fibers.
AB  - Diseases that result in muscle weakness, e.g., heart failure, are characterized
      by elevated sphingomyelinase (SMase) activity. In intact muscle, SMase increases
      oxidants that contribute to diminished muscle force. However, the source of
      oxidants, specific processes of muscle contraction that are dysfunctional, and
      biochemical changes underlying the weakness elicited by SMase remain unknown. We
      tested three hypotheses: 1) SMase-induced depression of muscle force is mediated
      by mitochondrial reactive oxygen species (ROS), 2) SMase depresses force and
      calcium sensitivity of the contractile apparatus, and 3) SMase promotes oxidation
      and phosphorylation of myofibrillar proteins. Our experiments included intact
      muscle bundles, permeabilized single fibers, and isolated myofibrillar proteins.
      The mitochondrial-targeted antioxidant d-Arg-2',6'-dimethyl-Tyr-Lys-Phe-NH(2),
      decreased cytosolic oxidants and protected intact muscle bundles from weakness
      stimulated by SMase. SMase depressed maximal calcium-activated force by 20% in
      permeabilized single fibers (in kN/m(2): control 117 +/- 6; SMase 93 +/- 8; P <
      0.05). Calcium sensitivity of permeabilized single fibers decreased from 5.98 +/-
      0.03 (control) to 5.91 +/- 0.02 (SMase; P < 0.05). Myofibrillar protein
      nitrotyrosines, carbonyls, and phosphorylation were unaltered by SMase. Our study
      shows that the fall in specific force of intact muscle elicited by SMase is
      mediated by mitochondrial ROS and can be attributed largely to dysfunction of the
      contractile apparatus.

PMID- 22362405
TI  - The rate of the deoxygenation reaction limits myoglobin- and hemoglobin
      facilitated O2 diffusion in cells.
AB  - A mathematical model describing facilitation of O(2) diffusion by the diffusion
      of myoglobin and hemoglobin is presented. The equations are solved numerically by
      a finite-difference method for the conditions as they prevail in cardiac and
      skeletal muscle and in red cells without major simplifications. It is
      demonstrated that, in the range of intracellular diffusion distances, the degree
      of facilitation is limited by the rate of the chemical reaction between myglobin
      or hemoglobin and O(2). The results are presented in the form of relationships
      between the degree of facilitation and the length of the diffusion path on the
      basis of the known kinetics of the oxygenation-deoxygenation reactions. It is
      concluded that the limitation by reaction kinetics reduces the maximally possible
      facilitated oxygen diffusion in cardiomyoctes by ~50% and in skeletal muscle
      fibers by ~ 20%. For human red blood cells, a reduction of facilitated O(2)
      diffusion by 36% is obtained in agreement with previous reports. This indicates
      that, especially in cardiomyocytes and red cells, chemical equilibrium between
      myoglobin or hemoglobin and O(2) is far from being established, an assumption
      that previously has often been made. Although the "O(2) transport function" of
      myoglobin in cardiac muscle cells thus is severely limited by the chemical
      reaction kinetics, and to a lesser extent also in skeletal muscle, it is
      noteworthy that the speed of release of O(2) from MbO(2), the "storage function,"
      is not limited by the reaction kinetics under physiological conditions.

PMID- 22362406
TI  - Effect of airway smooth muscle tone on airway distensibility measured by the
      forced oscillation technique in adults with asthma.
AB  - Airway distensibility appears to be unaffected by airway smooth muscle (ASM)
      tone, despite the influence of ASM tone on the airway diameter-pressure
      relationship. This discrepancy may be because the greatest effect of ASM tone on
      airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e.,
      low lung volumes, which has not been investigated. Our study aimed to determine
      the contribution of ASM tone to airway distensibility, as assessed via the forced
      oscillation technique (FOT), across all lung volumes with a specific focus on low
      lung volumes. We also investigated the accompanying influence of ASM tone on
      peripheral airway closure and heterogeneity inferred from the reactance versus
      lung volume relationship. Respiratory system conductance and reactance were
      measured using FOT across the entire lung volume range in 22 asthma subjects and
      19 healthy controls before and after bronchodilator. Airway distensibility (slope
      of conductance vs. lung volume) was calculated at residual volume (RV),
      functional residual capacity (FRC), and total lung capacity. At baseline, airway
      distensibility was significantly lower in subjects with asthma at all lung
      volumes. After bronchodilator, distensibility significantly increased at RV
      (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not
      in control subjects. The increased distensibility at RV and FRC in asthma were
      not associated with the accompanying changes in the reactance versus lung volume
      relationship. Our findings demonstrate that, at low lung volumes, ASM tone
      reduces airway distensibility in adults with asthma, independent of changes in
      airway closure and heterogeneity.

PMID- 22362407
TI  - Allosteric effects in a ditopic ligand containing bipyridine and tetra-aza-crown
      donor units.
AB  - Artificial allosterism: A ditopic ligand, which contains both bipyridine and
      tetra-aza-crown binding sites, coordinates one Cu(II) through all four N-donors
      of the tetradentate aza-crown unit. Reaction at the bipyridine site with another
      Cu(II) allosterically changes the aza-crown from being a tetradentate to a
      tridentate N-donor unit, a change in coordination mode that causes the successive
      binding of two Cu(II) ions to proceed with severe negative cooperativity (see
      scheme).

PMID- 22362408
TI  - Controlled cell death by magnetic hyperthermia: effects of exposure time, field
      amplitude, and nanoparticle concentration.
AB  - PURPOSE: To investigate the effects of alternating magnetic fields (AMF) on the
      death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as
      heating agents. AMF exposure time and amplitude as well as the MNPs concentration
      were screened to assess the best conditions for a controlled field-induced cell
      death. METHODS: Human-monocyte-derived DCs were co-incubated with dextran-coated
      MNPs. The cells were exposed to AMF (f = 260 kHz; 0 < H(0) < 12.7 kA/m) for
      intervals from 5 to 15 min. Morphology changes were assessed by scanning electron
      microscopy. Cell viability was measured by Trypan blue and fluorescence-activated
      cell sorting (FACS) using Annexin-propidium iodide markers. RESULTS: We were able
      to control the DCs viability by a proper choice AMF amplitude and exposure time,
      depending on the amount of MNPs uploaded. About 20% of cells showed Annexin
      negative/PI-positive staining after 5-10 min of AMF exposure. CONCLUSIONS:
      Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the
      physical AMF parameters and MNPs concentration. Necrotic-like populations were
      observed after exposure times as short as 10 min, suggesting a fast underlying
      mechanism for cell death. Power absorption by the MNPs might locally disrupt
      endosomic membranes, thus provoking irreversible cell damage.

PMID- 22362409
TI  - Bottlenecks caused by software gaps in miRNA and RNAi research.
AB  - Understanding the regulation of gene expression is critical to many areas of
      biology while control via RNAs has found considerable interest as a tool for
      scientific discovery and potential therapeutic applications. For example whole
      genome RNA interference (RNAi) screens and whole proteome scans provide views of
      how the entire transcriptome or proteome responds to biological, chemical or
      environmental perturbations of a gene's activity. Small RNA (sRNA) or MicroRNA
      (miRNA) are known to regulate pathways and bind mRNA, while the function of
      miRNAs discovered in experimental studies is often unknown. In both cases, RNAi
      and miRNA require labor intensive studies to tease out their functions within
      gene networks. Available software to analyze relationships is currently an ad hoc
      and often a manual process that can take up to several hours to analyze a single
      candidate RNAi or miRNA. With experiments frequently highlighting tens to
      hundreds of candidates this represents a considerable bottleneck. We suggest
      there is a gap in miRNA and RNAi research caused by inadequate current software
      that could be improved. For example a new software application could be created
      that provides interactive, comprehensive target analysis that leverages past
      datasets to lead to statistically stronger analyses.

PMID- 22362410
TI  - Dropouts in the AB/BA crossover design.
AB  - Missing data arise in crossover trials, as they do in any form of clinical trial.
      Several papers have addressed the problems that missing data create, although
      almost all of these assume that the probability that a planned observation is
      missing does not depend on the value that would have been observed; that is, the
      data are missing at random (MAR). In many applications, this assumption is likely
      to be untenable; in which case, the data are missing not at random (MNAR). We
      investigate the effect on estimates of the treatment effect that assume data are
      MAR when data are actually MNAR. We also propose using the assumption of no
      carryover treatment effect, which is usually required for this design, to permit
      the estimation of a treatment effect when data are MNAR. The results are applied
      to a trial comparing two treatments for neuropathic pain and show that the
      estimate of treatment effect is sensitive to the assumption of MAR.

PMID- 22362411
TI  - Robotic facelift thyroidectomy: Facilitating remote access surgery.
AB  - BACKGROUND: A novel remote access robotic thyroidectomy technique has been
      described that uses as its portal a postauricular and occipital hairline
      (facelift) incision. Experimental investigation and clinical validation have been
      completed. A detailed technical description is provided. METHODS AND MATERIALS: A
      young woman with a thyroid nodule was referred for surgery. Because of her
      concerns about a visible neck scar, she opted for remote access thyroidectomy.
      RESULTS: A left robotic facelift thyroidectomy was performed in less than 2 hours
      as a drainless, outpatient procedure. Videographic demonstration of the robotic
      resection is included. CONCLUSIONS: A number of remote access thyroidectomy
      techniques have proliferated. We developed and described an intuitive approach
      that uses familiar dissection planes and avoids the need for breast incisions and
      crossing the clavicle.

PMID- 22362412
TI  - Osteoporotic vertebral fractures without compression: key factors of diagnosis
      and initial outcome of treatment with cement augmentation.
AB  - INTRODUCTION: Because of the nonspecific symptoms and unapparent radiographic
      findings, occult osteoporotic vertebral fractures (VFs) have a high rate of
      missed diagnosis, and the treatment of these fractures has rarely been discussed
      in the literature. We investigated diagnostic key factors of such occult VFs and
      evaluated the effects of cement augmentation in these patients. METHODS: A total
      of 225 patients with VFs treated with vertebroplasty (VP) or kyphoplasty (KP)
      were retrospectively analyzed. All patients have taken preoperatively magnetic
      resonance imaging (MRI) including T1/T2-weighted images and short tau inversion
      recovery (STIR) sequences, and 45 patients met the inclusion criteria. Clinical
      outcomes were evaluated by comparing visual analog scale (VAS) and Oswestry
      disability index (ODI) values preoperatively, postoperatively, and at the final
      follow-up. RESULTS: MRI (T1 and STIR sequences) showed bone marrow edema in all
      fresh fractures including occult VFs and concomitant VFs; five patients showed no
      abnormality signal in their T2-weighted sequences of occult VFs. While 40
      patients underwent KP, and five patients underwent VP. We did not find delayed
      collapsed fractures in the augmented occult VFs in both groups after operation.
      Both groups had significant improvement in pain and functional activity after the
      intervention (p<0.01). CONCLUSION: The presence of previous or concomitant VFs
      leads to further imaging examination, which helps identify the occult VFs.
      Preoperative MRI examination especially T1 and STIR sequences plays a vital role
      in the early diagnosis of occult VFs. Except for significant pain relief and
      functional improvement, VP and KP can effectively prevent delayed vertebral
      collapse of occult VFs comparing to previous reported data.

PMID- 22362413
TI  - AR-Q640X, a model to study the effects of constitutively active C-terminally
      truncated AR variants in prostate cancer cells.
AB  - PURPOSE: A recently identified mechanism allowing prostate cancer (PCa) cells to
      grow in the absence of androgens is the expression of constitutively active, C
      terminally truncated androgen receptor (AR) variants lacking vast parts of the
      ligand-binding domain. These AR variants termed ARDeltaLBD are either products of
      alternative splicing, point mutations leading to premature stop codons or
      proteolytic cleavage of the AR. Some controversies exist about the requirement of
      additional full-length AR for the full transcriptional activity of the
      ARDeltaLBD. On basis of a mutated, C-terminally truncated AR termed Q640X, we
      developed an experimental model for the study of ARDeltaLBD in PCa cells.
      METHODS: Activation of AR-dependent promoters was analyzed by reporter gene
      assays. Dimerization studies were conducted using a mammalian two-hybrid system.
      RESULTS: Although Q640X/Q640X homodimers were able to induce the expression of
      certain AR target genes, Q640X/AR heterodimers were necessary to activate the
      full panel of androgen-dependent genes under androgen-deprived conditions.
      CONCLUSIONS: The following study supports the hypothesis that castration
      resistant prostate cancer (CRPC) cells are able to activate specific androgen
      dependent genes by selective modulation of the ratio between ARDeltaLBD and their
      putative dimerization partners like the full-length AR or other ARDeltaLBD in the
      absence of androgens. The present data suggest that AR-mutant Q640X is a powerful
      experimental tool for the functional analysis of ARDeltaLBD in CRPC.

PMID- 22362416
TI  - Hepatorenal syndrome: is it the magnitude of the renal failure that matters?

PMID- 22362414
TI  - Effect of the heat shock protein HSP27 on androgen receptor expression and
      function in prostate cancer cells.
AB  - PURPOSE: Heat shock proteins (HSP) are involved in processes of folding,
      activation, trafficking and transcriptional activity of most steroid receptors
      including the androgen receptor (AR). Accumulating evidence links rising heat
      shock protein 27 (HSP27) levels with the development of castration-resistant
      prostate cancer. In order to study the functional relationship between HSP27 and
      the AR, we modulated the expression of the small heat shock protein HSP27 in
      human prostate cancer (PC) cell lines. METHODS: HSP27 protein concentrations in
      LNCaP and PC-3 cells were modulated by over-expression or silencing of HSP27. The
      effects of HSP27 on AR protein and mRNA levels were monitored by Western blotting
      and quantitative RT-PCR. RESULTS: Treatment for the AR-positive LNCaP with HSP27
      specific siRNA resulted in a down-regulation of AR levels. This down-regulation
      of protein was paralleled by a decrease in AR mRNA. Most interestingly, over
      expression of HSP27 in PC-3 cells led to a significant increase in AR mRNA
      although the cells were unable to produce functional AR protein. CONCLUSION: The
      observation that HSP27 is involved in the regulation of AR mRNA by a yet unknown
      mechanism highlights the complexity of HSP27-AR signaling network.

PMID- 22362418
TI  - Fluorescent amphiphilic cellulose nanoaggregates for sensing trace explosives in
      aqueous solution.
AB  - A novel fluorescent amphiphilic cellulose nanoaggregates sensing system is
      designed and applied in detecting explosives in aqueous solution. Due to the
      maximized interaction between sensing material and analyte within the cellulose
      based nanoaggregates, significantly enhanced sensitivity with 50-fold higher
      quenching efficiency is obtained.

PMID- 22362417
TI  - Tumor-promoting macrophages induce the expression of the macrophage-specific
      receptor CD163 in malignant cells.
AB  - Tumor-associated macrophages (TAMs) represent a distinct malignancy-promoting
      phenotype suggested to play a key role in tumor formation and metastasis. We
      aimed to investigate the expression of the monocyte/macrophage-restricted
      receptor CD163 in bladder tumor biopsies and assess the potential mechanism
      inducing the CD163 expression in tumor cells. A high CD163 mRNA expression (n =
      87) was significantly associated with a poor 13-year overall survival (log-rank
      test, chi(2)  = 8.931; p = 0.0028). Moreover, CD163 mRNA expression was
      significantly increased in muscle invasive (T2-T4), p = 0.017, and aggressive
      (grade III/IV) cancers (p = 0.015). The expression strongly correlated with local
      expression of IL-6 (r = 0.72; p <0.0001) and IL-10 (r = 0.75; p <0.0001),
      mediators known to induce CD163 expression in vitro. CD163 immunostaining (n =
      46) confirmed the association between dense TAM infiltration and histologically
      advanced disease. In 39% of the biopsies, CD163 immunoreactivity was also
      observed in tumor cells, and CD163-expressing metastatic cells were identified in
      lymph node biopsies (n = 8). Bladder cancer cell lines did not express CD163;
      however, when cocultured with macrophages the bladder cancer cell expression of
      CD163 was significantly induced in an IL-6/IL-10 independent manner. In
      conclusion, we show a strong association between CD163 mRNA expression in bladder
      cancer biopsies and poor patient outcome. CD163 expression was not confined to
      the infiltrating TAMs, but was also expressed by a significant portion of the
      malignant cells in both tumors and lymph nodes. CD163 expressing tumor cells may
      constitute a subpopulation of tumor cells with a phenotypic shift associated with
      epithelial-to-mesenchymal transition (EMT) and increased metastatic activity
      induced by TAMs.

PMID- 22362419
TI  - PolyIC GE11 polyplex inhibits EGFR-overexpressing tumors.
AB  - Phage display has identified the dodecapeptide YHWYGYTPQNVI (GE11) as a ligand
      that binds to the epidermal growth factor receptor (EGFR) but does not activate
      the receptor. Here, we compare the EGFR binding affinities of GE11, EGF, and
      their polyethyleneimine-polyethyleneglycol (PEI-PEG) conjugates. We found that
      although GE11 by itself does not exhibit measurable affinity to the EGFR,
      tethering it to PEI-PEG increases its affinity markedly, and complex formation
      with polyinosine/cytosine (polyIC) further enhances the affinity to the
      submicromolar range. PolyIC/PPGE11 has a similar strong antitumor effect against
      EGFR overexpressing tumors in vitro and in vivo, as polyIC/polyethyleneimine
      polyetheleneglycol-EGF (polyIC/PP-EGF). Absence of EGFR activation, as previously
      shown by us and easier production of GE11 and GE11 conjugates, confer
      polyIC/PPGE11 a significant advantage over similar EGF-based polyplexes as a
      potential therapy of EGFR overexpressing tumors.

PMID- 22362420
TI  - Double pass 595 nm pulsed dye laser at a 6 minute interval for the treatment of
      port-wine stains is not more effective than single pass.
AB  - BACKGROUND: Pulsed dye laser (PDL) is the first choice for treatment of port wine
      stains (PWS). However, outcome is highly variable and only a few patients achieve
      complete clearance. The objective of the study was to compare efficacy and safety
      of single pass PDL with double pass PDL at a 6 minute interval. METHODS: We
      conducted a randomized within-patient controlled study on PWS resistant to
      multiple single pass PDL treatments. In each patient two similar PWS areas were
      randomly allocated to PDL treatment (595 nm, 7 mm spot size, 1.5 mseconds pulse
      duration) using, as a control treatment, a single pass (12 J/cm(2)) or, as a new
      treatment, a double pass PDL (11 J/cm(2), second pass 6 minutes after the first
      pass). Both test areas were treated two times, 8 weeks apart. PWS clearance was
      assessed by two blinded dermatologists, and by color measurement (L*a*b) using
      reflectance spectroscopy, at 3 months follow-up. RESULTS: Sixteen out of 17
      included patients completed follow-up. The mean number of treatments before
      inclusion was 15. Overall color assessed by spectrophotometer showed no
      improvement for either single or double pass PDL. Blinded Physician Global
      Assessment and Patient Global Assessment showed a high variability in outcome,
      with mostly only moderate improvement of the PWS for either single pass or double
      pass PDL. Furthermore, there was no significant difference in any of the outcomes
      between single pass and double pass PDL. CONCLUSION: At the chosen settings and
      after two treatment sessions, double pass PDL at a 6 minute interval does not
      result in improved clearance of PWS as compared to single pass treatment.

PMID- 22362421
TI  - Diaphragmatic injuries after blunt trauma: are they still a challenge? Reviewing
      CT findings and integrated imaging.
AB  - Traumatic diaphragmatic rupture is a life-threatening injury that may occur in
      patients with blunt trauma. At present, supine chest radiographs is the initial,
      most commonly performed imaging test to evaluate a traumatic injury of the
      thorax. However, computed tomography (CT) is the imaging tool of choice, as it is
      the 'gold standard' for the detection of diaphragmatic injury after trauma. In
      particular, recent literature indicates that multidetector CT with multiplanar
      reformations has significantly improved in accuracy. Radiologists working in the
      emergency room should keep in mind the possibility of diaphragmatic injuries and
      should routinely integrate the axial images CT with multiplanar reformations in
      order to detect any potential, subtle or doubtful sign of incomplete
      diaphragmatic injury.

PMID- 22362422
TI  - Early assessment of the efficacy of digital infrared thermal imaging in pediatric
      extremity trauma.
AB  - Young children or those with intellectual disability with trauma to an extremity
      often undergo radiographs of the whole limb. The objective of the study was to
      assess the efficacy of digital infrared thermal images (DITI) in pediatric
      extremity trauma. We hypothesized fractures to be associated with local
      hyperthermia, detectable with DITI, which could direct focused radiographs. In
      this exploratory study, patients seen over a 2-month period in a pediatric
      emergency department for limb trauma were included if an extremity radiograph was
      taken on the same day. Patients had DITI of symptomatic and contralateral limbs.
      The warmest area of each image was compared to the site of pain and/or fracture
      on the radiograph. Fifty-one patients were enrolled. DITI matched 73% of pain
      sites. Fractures were seen in 11 patients. DITI matched 7 of 11 (64%) fracture
      sites. DITI performance in pinpointing the site of injury, although suboptimal,
      is encouraging for further evaluation.

PMID- 22362423
TI  - Models that matter: white matter stroke models.
AB  - Stroke is a devastating neurological disease with limited functional recovery.
      Stroke affects all cellular elements of the brain and impacts areas traditionally
      classified as both gray matter and white matter. In fact, stroke in subcortical
      white matter regions of the brain accounts for approximately 30% of all stroke
      subtypes, and white matter injury is a component of most classes of stroke
      damage. However, most basic scientific information in stroke cell death and
      neural repair relates principally to neuronal cell death and repair. Despite an
      emerging biological understanding of white matter development, adult function,
      and reorganization in inflammatory diseases, such as multiple sclerosis, little
      is known of the specific molecular and cellular events in white matter ischemia.
      This limitation stems in part from the difficulty in generating animal models of
      white matter stroke. This review will discuss recent progress in studies of
      animal models of white matter stroke, and the emerging principles of cell death
      and repair in oligodendrocytes, axons, and astrocytes in white matter ischemic
      injury.

PMID- 22362426
TI  - Long-term tracking of cells using inorganic nanoparticles as contrast agents: are
      we there yet?
AB  - The use of inorganic nanoparticles as probes to label and track cells in vivo is
      already a reality. While superparamagnetic nanoparticles have been the subject of
      clinical studies involving magnetic resonance imaging, quantum dots and gold
      nanoparticles are starting to be explored for similar goals in pre-clinical
      studies involving fluorescence and photoacoustic imaging. Although exciting
      results have been obtained from in vivo investigations, there appears to be a
      general lack of understanding on the effects of physicochemical properties on the
      labelling efficiency and toxicity of those nanoparticles, as well as on their
      stability in the intracellular microenvironment; essential requirements for using
      them as probes for cellular tracking. In this tutorial review, we look at what
      the current literature can teach us in respect to cell interactions with these
      nanoparticles, with the perspective of using them as probes for cell labelling.
      We also examine the findings obtained in pre-clinical studies that expose
      potential misinterpretation that can occur when using inorganic nanoparticles for
      in vivo imaging.

PMID- 22362425
TI  - Involvement of 5-HT2A receptor and alpha2-adrenoceptor blockade in the asenapine
      induced elevation of prefrontal cortical monoamine outflow.
AB  - The psychotropic drug asenapine is approved for the treatment of schizophrenia
      and manic or mixed episodes associated with bipolar I disorder. Asenapine
      exhibits higher affinity for several 5-HT receptors and alpha(2)-adrenoceptors
      than for D(2) receptors. Noteworthy, blockage of both the 5-HT(2A) and alpha(2)
      adrenergic receptors has been shown to enhance prefrontal dopamine release
      induced by D(2) receptor antagonists. Previous results show that asenapine, both
      systemically and locally, increases dopamine, noradrenaline, and serotonin
      release in the medial prefrontal cortex (mPFC), and that the increased dopamine
      release largely depends on an intracortical action. Using reverse microdialysis
      in freely moving rats, we here assessed the potency of low concentrations of
      asenapine to cause a pharmacologically significant blockage in vivo of 5-HT(2A)
      receptors and alpha(2)-adrenoceptors within the mPFC, and thus its ability to
      affect cortical monoamine release by these receptors. Intracortical
      administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride
      (DOI), a 5-HT(2A/2C) receptor agonist, increased cortical monoamine release,
      effects that were antagonized both by asenapine and the selective 5-HT(2A)
      antagonist M100907. Application of clonidine, an alpha(2)-adrenoceptor agonist,
      significantly reduced monoamine release in the mPFC. The selective alpha(2)
      adrenoceptor antagonist idazoxan blocked, whereas asenapine partially blocked
      clonidine-induced cortical dopamine and noradrenaline decrease. The effects of
      asenapine and idazoxan on clonidine-induced serotonin decrease were less
      pronounced. Our results propose that low concentrations of asenapine in the mPFC
      exhibit a pharmacologically significant 5-HT(2A) and alpha(2) receptor
      antagonistic activity, which may contribute to enhance prefrontal monoamine
      release in vivo and, secondarily, its clinical effects in schizophrenia and
      bipolar disorder.

PMID- 22362424
TI  - Genetic manipulation of cell death and neuroplasticity pathways in traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) initiates a complex cascade of secondary
      neurodegenerative mechanisms contributing to cell dysfunction and necrotic and
      apoptotic cell death. The injured brain responds by activating endogenous
      reparative processes to counter the neurodegeneration or remodel the brain to
      enhance functional recovery. A vast array of genetically altered mice provide a
      unique opportunity to target single genes or proteins to better understand their
      role in cell death and endogenous repair after TBI. Among the earliest targets
      for transgenic and knockout studies in TBI have been programmed cell death
      mediators, such as the Bcl-2 family of proteins, caspases, and caspase
      independent pathways. In addition, the role of cell cycle regulatory elements in
      the posttraumatic cell death pathway has been explored in mouse models. As
      interest grows in neuroplasticity in TBI, the use of transgenic and knockout mice
      in studies focused on gliogenesis, neurogenesis, and the balance of growth
      promoting and growth-inhibiting molecules has increased in recent years. With
      proper consideration of potential effects of constitutive gene alteration,
      traditional transgenic and knockout models can provide valuable insights into TBI
      pathobiology. Through increasing sophistication of conditional and cell-type
      specific genetic manipulations, TBI studies in genetically altered mice will be
      increasingly useful for identification and validation of novel therapeutic
      targets.

PMID- 22362427
TI  - Variance estimation for stratified propensity score estimators.
AB  - Propensity score methods are increasingly used to estimate the effect of a
      treatment or exposure on an outcome in non-randomised studies. We focus on one
      such method, stratification on the propensity score, comparing it with the method
      of inverse-probability weighting by the propensity score. The propensity score-
      the conditional probability of receiving the treatment given observed covariates-
      is usually an unknown probability estimated from the data. Estimators for the
      variance of treatment effect estimates typically used in practice, however, do
      not take into account that the propensity score itself has been estimated from
      the data. By deriving the asymptotic marginal variance of the stratified estimate
      of treatment effect, correctly taking into account the estimation of the
      propensity score, we show that routinely used variance estimators are likely to
      produce confidence intervals that are too conservative when the propensity score
      model includes variables that predict (cause) the outcome, but only weakly
      predict the treatment. In contrast, a comparison with the analogous marginal
      variance for the inverse probability weighted (IPW) estimator shows that
      routinely used variance estimators for the IPW estimator are likely to produce
      confidence intervals that are almost always too conservative. Because exact
      calculation of the asymptotic marginal variance is likely to be complex,
      particularly for the stratified estimator, we suggest that bootstrap estimates of
      variance should be used in practice.

PMID- 22362428
TI  - College students and suicide risk: prevention and the role of academic
      psychiatry.

PMID- 22362429
TI  - The state of medical student wellness: a call for culture change.

PMID- 22362430
TI  - Burnout in premedical undergraduate students.
AB  - BACKGROUND: There has been growing recognition that medical students, interns,
      residents and practicing physicians across many specialties are prone to burnout,
      with recent studies linking high rates of burnout to adverse mental health
      issues. Little is known about the trajectory and origins of burnout or whether
      its roots may be traced to earlier in medical training, specifically, during
      undergraduate studies. Here, the authors surveyed undergraduates at UC San Diego
      (UCSD) to assess the relationship of burnout to premedical status while
      controlling for depression severity. METHODS: Undergraduate students at UCSD were
      invited to participate in a web-based survey, consisting of demographic
      questions; the Maslach Burnout Inventory Student Survey (MBI-SS), which gauged
      the three dimensions of burnout; and the nine-item Patient Health Questionnaire
      (PHQ-9), to assess depression severity. RESULTS: A total of 618 premedical
      students and 1,441 non-premedical students completed the questionnaire.
      Premedical students had greater depression severity and emotional exhaustion than
      non-premedical students, but they also exhibited a greater sense of personal
      efficacy. The burnout differences were persistent even after adjusting for
      depression. Also, premedical women and Hispanic students had especially high
      levels of burnout, although differences between groups became nonsignificant
      after accounting for depression. CONCLUSIONS: Despite the limitations of using a
      burnout questionnaire not specifically normed for undergraduates, the unique
      ethnic characteristics of the sample, and the uncertain response rate, the
      findings highlight the importance of recognizing the unique strains and mental
      health disturbances that may be more common among premedical students than non
      premedical students. Results also underscore the close relationship between
      depression and burnout, and point the way for subsequent longitudinal, multi
      institutional studies that could help identify opportunities for prevention and
      intervention.

PMID- 22362431
TI  - Conflict of interest and disclosure policies in psychiatry and medicine: a
      comparative study of peer-reviewed journals.
AB  - OBJECTIVE: The authors reviewed and characterized conflict of interest (COI) and
      disclosure policies published in peer-reviewed psychiatric and nonpsychiatric
      journals. METHODS: The authors examined peer-reviewed publications in the
      psychiatric (N=20) and nonpsychiatric (N=20) literature. Using qualitative and
      quantitative approaches, they designed an instrument to compare COI and
      disclosure policies appearing in print or journal websites between January and
      May 2009. RESULTS: All journals published COI/disclosure policies that were
      accessible in print and online. There was substantial variability in policies,
      but little variability appeared to be field-specific. Psychiatric journals were
      more likely to request "complete" disclosure, and nonpsychiatric journals to
      request "relevant" disclosure, but medical journals tended to provide more
      detailed information about what could constitute a potential conflict and asked
      for broader, potentially relevant funding sources. Nonpsychiatric journals were
      more likely to give examples in their policies. Psychiatric journals were more
      likely to publish disclosures. CONCLUSION: This preliminary study suggests that
      there are discrepancies in the disclosure and COI information that journals
      request from authors. By and large, such discrepancies are not substantially
      different between psychiatric and nonpsychiatric journals. Challenges in
      codifying COI policies and creating standardized approaches across periodicals
      and across disciplines may reflect ongoing debates about what exactly constitutes
      a COI, what needs to be disclosed, and who is responsible for disclosing. Further
      study is warranted into how journals convey COI policies and how such policies
      can be optimized.

PMID- 22362432
TI  - A method for evaluating competency in assessment and management of suicide risk.
AB  - OBJECTIVE: Although health professionals increasingly are expected to be able to
      assess and manage patients' risk for suicide, few methods are available to
      evaluate this competency. This report describes development of a competency
      assessment instrument for suicide risk-assessment (CAI-S), and evaluates its use
      in an objective structured clinical examination (OSCE). METHOD: The authors
      developed the CAI-S on the basis of the literature on suicide risk-assessment and
      management, and consultation with faculty focus groups from three sites in a
      large academic psychiatry department. The CAI-S structures faculty ratings
      regarding interviewing and data collection, case formulation and presentation,
      treatment-planning, and documentation. To evaluate the CAI-S, 31 faculty members
      used it to rate the performance of 31 learners (26 psychiatric residents and 5
      clinical psychology interns) who participated in an OSCE. After interviewing a
      standardized patient, learners presented their risk-assessment findings and
      treatment plans. Faculty used the CAI-S to structure feedback to the learners. In
      a subsidiary study of interrater reliability, six faculty members rated video
      recorded suicide risk-assessments. RESULTS: The CAI-S showed good internal
      consistency, reliability, and interrater reliability. Concurrent validity was
      supported by the finding that CAI-S ratings were higher for senior learners than
      junior learners, and were higher for learners with more clinical experience with
      suicidal patients than learners with less clinical experience. Faculty and
      learners rated the method as helpful for structuring feedback and supervision.
      CONCLUSION: The findings support the usefulness of the CAI-S for evaluating
      competency in suicide risk-assessment and management.

PMID- 22362433
TI  - Coping with a patient's suicide: a curriculum for psychiatry residency training
      programs.
AB  - OBJECTIVE: The suicide of a patient is often experienced as a traumatic event by
      the clinician involved. Many articles have identified the need for education to
      guide clinicians through the aftermath of patient suicide; however, little has
      been published on development of such a curriculum, particularly for residents.
      This article describes one residency training program's development of an
      organized curriculum on coping with patient suicide and evaluates the impact of a
      core aspect of the training on clinicians' knowledge about and confidence with
      coping with patient suicide. METHODS: The training includes a biennial half-day
      workshop for all trainees plus an "as-needed curriculum" used after a completed
      suicide. A total of 42 clinicians (39 psychiatry residents and 3 psychiatry
      faculty) participated in a workshop on coping with patient suicide. Their
      attitudes and knowledge about the topic were assessed before and after the
      training. RESULTS: Participation in the workshop was associated with large and
      statistically significant increases in knowledge and self-perceptions of
      competence in coping with patient suicide. CONCLUSIONS: The addition of a
      curriculum on coping with patient suicide has the potential to significantly
      enhance psychiatric residency training.

PMID- 22362434
TI  - Patient suicides in psychiatric residencies and post-vention responses: a
      national survey of psychiatry chief residents and program directors.
AB  - OBJECTIVES: This report focuses on post-vention measures taken by U.S. psychiatry
      residencies when a resident-in-training experiences a patient suicide. METHODS: A
      survey distributed to program directors and chief residents obtained an estimate
      of the frequency of psychiatric residents' experiencing a patient suicide and the
      frequency of numerous post-vention activities utilized by psychiatric residencies
      in 2008. The survey looked at the presence or absence of a post-vention protocol
      within a program and determined whether there was an effect on the number of
      patient suicides and the frequency of post-vention activities within a program.
      The data were compared with the results of a similar survey from 1994 to
      determine whether there had been significant progress in the practice of
      supportive post-vention activities within training institutions. RESULTS: There
      was a 21% response rate from chief residents (N=54) and a 31.1% response rate
      from program directors (N=94). Chief residents reported 1.44 suicides per
      residency, and program directors reported 0.88 suicides per residency for the
      2008 calendar year. This corresponded to approximately 1 in 20 residents'
      experiencing a patient suicide in the 12-month period. Both groups reported
      approximately 1 in 5 psychiatry residency programs with written post-vention
      protocols, which was unchanged from the 1994 survey. When a protocol was in
      place, chief residents reported a statistically significant increase in timely
      notification of the program director, process groups, therapy or counseling, and
      emergency leave, whereas program directors reported a statistically significant
      decrease in post-vention therapy or counseling. Further statistical analysis
      revealed a tendency for programs with post-vention protocols to have more
      reported suicides. CONCLUSIONS: Post-vention protocols may be developed by
      residencies as a need to address residents experiencing a patient suicide.
      Discrepancies in the reports of chief residents and program directors in post
      vention activities may reflect a lack of consensus on post-vention training and
      education within psychiatric residencies.

PMID- 22362435
TI  - Survey of threats and assaults by patients on psychiatry residents.
AB  - OBJECTIVE: The authors sought to determine the prevalence of threats and assaults
      by patients on psychiatry residents, their consequences, and the perceived
      adequacy of supports and institutional responses. METHOD: Authors conducted an
      anonymous survey of 519 psychiatry residents in 13 psychiatry programs across the
      United States. The survey questionnaire inquired about residents' experiences of
      threats and assaults by patients during their residency training. RESULTS: The
      response rate for this survey was 39% (N=204). Residents were most commonly
      threatened (N=175; 86%), physically intimidated (N=145; 71%) or received unwanted
      advances (N=118; 58%). One-quarter (N=51; 25%) were physically assaulted. Most of
      the incidents occurred in inpatient settings (N=92; 45%). CONCLUSION: This study,
      like previous studies on this topic, calls attention to the high number of
      residents that are affected by violence during their training, and it underscores
      the need to protect the safety of psychiatry residents and to support those who
      have been victimized.

PMID- 22362436
TI  - Evaluating the workload of on-call psychiatry residents: which activities are
      associated with sleep loss?
AB  - OBJECTIVE: The purpose of this study was to review the workload inventory of on
      call psychiatry residents and to evaluate which activities were associated with
      reductions in on-call sleep. METHOD: A prospective cohort study was conducted,
      following 20 psychiatry residents at a 231-bed psychiatry hospital, from July 1,
      2008 through June 30, 2009. On-call activities and hours of sleep received were
      recorded on log sheets. RESULTS: From the 2008-2009 academic year, 298 on-call
      log sheets were received (81.64% response rate). The mean hours of sleep per
      night received by participating residents was 3.52 hours. The mean number of
      pages received was 17.21 per night. The variance in hours of sleep was explained
      by the number of pages and the number of admissions. CONCLUSION: Given the new
      standards established by the Accreditation Council for Graduate Medical
      Education, residency directors can increase on-call sleep for residents by
      reducing the number of pages and admissions.

PMID- 22362437
TI  - Capacity-building for African American mental health training and research:
      lessons from the Howard-Dartmouth Collaborative summer school.
AB  - BACKGROUND: Many psychiatric residents have traditionally received little-or-no
      training in cross cultural approaches to psychiatric training and research.
      METHOD: The Dartmouth-Howard Collaboration summer school training program had a 5
      year grant to explore approaches to enhancing understanding of cultural factors
      in mental health treatment and research. RESULTS: Participants' questionnaire
      rating responses indicated that their experience in the Summer School program
      enhanced their understanding and experience in dealing with minority, largely
      African American patients and the diverse factors that affect their treatment.
      CONCLUSION: The Dartmouth-Howard Collaboration provides a model for a feasible
      training program that imparts knowledge regarding culture and mental health, and
      the conduct of mental health research, with particular attention to African
      American mental health. The program is unique in that it offers an intense, 1
      week course delivered to several types of mental health professionals and
      trainees in research and practice.

PMID- 22362438
TI  - Psychiatry in the Deep South: a pilot study of integrated training for psychiatry
      residents and seminary students.
AB  - OBJECTIVE: The authors describe an interdisciplinary training experience
      developed for psychiatry residents and seminary students that assessed each
      group's beliefs and attitudes toward the other's profession. The training was
      designed to enhance awareness, positive attitudes, and interaction between the
      disciplines. METHODS: From 2005 to 2008, PGY-2 general-psychiatry residents and
      PGY-5 child-psychiatry residents (N=30) participated alongside psychology interns
      (N=13) and seminary students (N=41). The intervention consisted of two 3-hour
      sessions. Measurements addressed demographics, participants' spirituality, and
      attitudes toward mental illness, mental-health practitioners, and clergy.
      RESULTS: The psychiatry residents' knowledge regarding the training of clergy was
      significantly increased by the training sessions. The seminary students'
      attitudes and knowledge of psychiatry/psychology changed significantly in a
      positive direction. CONCLUSION: This pilot course had a positive impact on both
      groups of participants. This model could be modified for other psychiatry
      programs, to include clergy students of different religious faiths as relevant to
      the demographics of the training location.

PMID- 22362439
TI  - Spirituality training in residency: changing the culture of a program.

PMID- 22362440
TI  - The Texas Regional Psychiatry Minority Mentor Network: a regional effort to
      increase psychiatry's workforce diversity.

PMID- 22362441
TI  - Depression, anxiety, and stress among last-year students at Erciyes University
      Medical School.

PMID- 22362442
TI  - The status of pain medicine education in psychiatry: a survey of residency
      training program directors.

PMID- 22362443
TI  - Perspectives on geriatric psychiatry: results of a single site survey of
      psychiatry residents.

PMID- 22362444
TI  - Assessing the practices and perceptions of dually-trained physicians: a pilot
      study.

PMID- 22362445
TI  - Medical students learning reflection and interpersonal skills.

PMID- 22362446
TI  - Sexting: the impact of a cultural phenomenon on psychiatric practice.

PMID- 22362448
TI  - Organization of care for pancreatic cancer.
AB  - THE ABSTRACT IS AVAILABLE AT THE CLINICAL PANCREATIC DISORDER I: Acute
      pancreatitis. North Am J Med Sci 2011; 3: 316-319. doi: 10.4297/najms.2011.3316.

PMID- 22362447
TI  - Involvement of proteasome beta1i subunit, LMP2, on development of uterin
      leiomyosarcma.
AB  - BACKGROUND: Although the majority of smooth muscle neoplasms found in the uterus
      are benign, uterine leiomyosarcoma is extremely malignant, with high rates of
      recurrence and metastasis. The development of gynecologic tumors is often
      correlated with secretion of female hormone; however, the development of human
      uterine leiomyosarcoma is not substantially correlated with hormonal conditions,
      and the risk factors are unclearly understood. Importantly, a diagnostic
      biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign
      tumor leiomyoma is yet to be established. AIMS: It is necessary to analyze risk
      factors associated with human uterine leiomyosarcoma, in order to establish a
      diagnostic-biomarker and a clinical treatment method. PATIENTS AND METHODS:
      HISTOLOGY AND IMMUNOFLUORESCENCE STAINING: Uteri obtained from LMP2(-/-) mice or
      its parental mice (C57BL/6 mice) were fixed in 10% buffered formalin, incubated
      in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections (5
      MUm) were prepared and stained with H&E for routine histological examination or
      were processed further for immunofluorescence staining with appropriate
      antidodies. Furthermore, a total of 101 patients between 32 and 83 years of age
      and diagnosed as having smooth muscle tumors of the uterus were selected from
      pathological files. Immunohistochemistry staining for LMP2 was performed on
      serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. RESULTS:
      Homozygous deficient mice for a proteasome beta1i subunit, LMP2 spontaneously
      develop uterine leiomyosarcoma, with a disease prevalence of ~40% by 14 months of
      age. Defective LMP2 expression in human uterine leiomyosarcoma was demonstrated,
      but present in human leiomyoma and myometrium. CONCLUSIONS: Loss in LMP2
      expression may be one of the risk factors for human uterine leiomyosarcoma. LMP2
      may be a potential diagnostic-biomarker and targeted-molecule for a new
      therapeutic approach.

PMID- 22362449
TI  - Practices of Lebanese gynecologists regarding treatment of recurrent vulvovaginal
      candidiasis.
AB  - BACKGROUND: A review of the literature clearly indicates the absence of one set
      of guideline in the treatment of recurrent vulvovaginal candidiasis. In Lebanon,
      as physicians are trained in European or American schools of medicine, locally or
      abroad, they may be approaching the issue of recurrent vulvovaginal candidiasis
      using various methods. AIMS: A national survey was conducted among Lebanese
      gynecologists to assess therapeutic protocols most commonly adopted to treat
      recurrent vulvovaginal candidiasis. MATERIAL AND METHODS: All obstetricians
      gynecologists registered with the Order of Physicians were targeted. Bivariate
      analyses, comparing groups with specific prescription preferences, were tested
      using relevant statistical tests. All variables with significant bivariate
      associations with the outcomes were initially planned for a multivariate
      regression analysis to assess their interactive effects. RESULTS: The study
      confirms that different approaches are used to treat recurrent vulvovaginal
      candidiasis. Most gynecologists (70%) recommended fluconazole 150 mg as first
      line treatment. Fluconazole alone was significantly preferred by North American
      trained physicians, whereas European trained ones preferred to prescribe it in
      combination. However different dosage regimens were used with duration of
      treatment ranging from 2 to 4 weeks, with or without maintenance. CONCLUSIONS:
      The study revealed large diversity in prescription pattern, closely related to
      the specialization background of the physician. There is a need to generate
      evidence to establish national guidelines.

PMID- 22362450
TI  - The antiatherogenic, renal protective and immunomodulatory effects of purslane,
      pumpkin and flax seeds on hypercholesterolemic rats.
AB  - BACKGROUND: Atherosclerosis remains one of the leading causes of death all over
      the world. Flax, pumpkin and purslane seeds are rich sources of unsaturated fatty
      acids, antioxidants and fibers, known to have antiatherogenic activities. AIMS:
      This study was to examine the efficiency of using either flax/pumpkin or
      purslane/pumpkin seed mixture (components of omega-3 and omega-6) on
      hyperlipidemia, kidney function and as immunomodulators in rats fed high
      cholesterol diets. MATERIALS AND METHODS: 40 male albino rats were divided into
      four groups: control group, hypercholesterolemic rats, fed the balanced diet
      supplemented with cholesterol at a dose level of 2 g/100 g diet; the other two
      groups of animals fed the same previous hypercholesterolemic diet supplemented
      with either flax/pumpkin seed mixture or pumpkin/purslane seed mixture at ratio
      of (5/1) (omega-3 and omega-6). RESULTS: The present study showed that 2%
      cholesterol administration caused a significant increase in total cholesterol,
      total lipids, and triacylglycerol in both serum and liver. Serum phospholipids,
      LDL-C, and atherogenic index AI also significantly increased compared to control
      group. Cholesterol-enriched diet significantly increased serum urea, creatinine,
      sodium and potassium levels as well as significantly increased serum IgG and IgM
      compared to healthy control. Consumption of flax/pumpkin or purslane/pumpkin seed
      mixtures by hypercholesterolemic rats resulted in a significantly decrement in
      lipid parameters and significant improvement in IgG and IgM levels as compared
      with hypercholesterolemic rats. CONCLUSION: Our results suggests that both
      flax/pumpkin and purslane/pumpkin seed mixtures had anti-atherogenic
      hypolipidemic and immunmodulator effects which were probably mediated by
      unsaturated fatty acids (including alpha linolenic acid) present in seed mixture.

PMID- 22362451
TI  - Medication adherence in diabetes mellitus and self management practices among
      type-2 diabetics in Ethiopia.
AB  - BACKGROUND: Type-2 diabetes mellitus and its complication are becoming more
      prevalent in Ethiopia. Evidence abound that the most important predictor of
      reduction of morbidity and mortality due to diabetes complication is the level of
      glycemic control achieved. AIMS: The aim is to assess adherence to anti diabetic
      drug therapy and self management practice among type-2 diabetic patient in
      Ethiopia. PATIENTS AND METHOD: The study consists of two phases. A cross
      sectional review of randomly selected 384 case notes of type-2 diabetic patient
      that attend diabetes mellitus clinic over 3 month and cross-sectional interview,
      with pre tested adherence and self management and monitoring tool questioner of
      347 consecutive patients that attend in Jimma university specialized hospital
      diabetic clinic. RESULT: Oral hypoglycemic agent were prescribed for 351(91.4) of
      the patient while insulin and oral hypoglycemic agent was prescribed in 33(8.6%).
      About 312 (88.9%) patients on oral hypoglycemic agent were on mono therapy, the
      most frequently prescribed oral hypoglycemic agent was glibenclamide 232(74.3%)
      and metformine 80(25.7%). Only 41.8% of the patient had adequate glycemic
      control. The main external factors for non adherence were lack of finance (37.1%)
      followed by perceived side effect of drug 29.2%. Only 6.5% patient who missed
      their medications disclosed to physician during consultation. The knowledge and
      practice of critical component of diabetes self management behavior were
      generally low among the patient studied. CONCLUSION: Majority of the patient with
      type 2 diabetes in Ethiopia are managed by OHA monotherapy mainly glybenclamide
      and metformine. While the current prescribing strategy do not achieve glycemic
      control on majority of the patient. This is due to poor adherence with the
      prescribed drug regimen and poor knowledge and practice of successful self
      management.

PMID- 22362452
TI  - Assessment of the risk status of pregnant women presenting for antenatal care in
      a rural health facility in Ebonyi State, South Eastern Nigeria.
AB  - BACKGROUND: Nigeria has one of the worst maternal and child health indices
      globally. AIMS: The objective of this study was to assess the risk status of
      pregnant women presenting for antenatal care in a rural health facility in Ebonyi
      State, South East Nigeria. SUBJECTS AND METHOD: This was a cross-sectional
      descriptive study of pregnant women selected by systematic random sampling. The
      study instrument was a pre-tested semi-structured interviewer-administered
      questionnaire. RESULT: The age range of the women in the study was 16-43 years.
      The mean age was 25.3 +/- 1.3 years. According to the scoring system used, about
      one-fourth of the women (26%) had a high risk pregnancy while about a tenth
      (9.1%) had very high risk pregnancy. The vast majority of the women with at-risk
      pregnancies registered for antenatal care late: 58.9 % registered for antenatal
      care in the second trimester and 37.0 % registered for antenatal care in the
      third trimester of pregnancy. Of the women with an at-risk pregnancy, 79.5% had
      their last delivery at home and 67.1 % of them preferred to deliver at home in
      their current pregnancies. CONCLUSION: This study revealed that a substantial
      proportion of rural women with at-risk pregnancies go through their pregnancy
      period without significant modern antenatal care. The local government health
      department should intensify efforts through health enlightenment campaigns to
      educate rural pregnant women of the benefits of utilizing modern antenatal care
      services.

PMID- 22362453
TI  - Recurrent pneumothorax: A rare complication of miliary tuberculosis.
AB  - CONTEXT: Recurrent pneumothorax is common in cavitory pulmonary tuberculosis, but
      it is extremely rare in miliary tuberculosis. CASE REPORT: A 25 year old female
      patient presented to us with the complains of shortness of breath since 3 days.
      She was also having fever and cough since 3 months. Chest roentgenogram (PA view)
      on admission showed a left sided pneumothorax with miliary mottling. An
      intercostals tube drainage was done on the left side resulting in relief of
      symptoms. Two days post intercostals tube drainage chest X ray (PA view) showed
      complete resolution of pneumothorax, and intercostals tube was removed. Patient
      was discharged on antitubercular drugs. After 1 month patient again presented to
      us with severe breathlessness, on repeat chest X ray pneumothorax again developed
      on left side, urgent intercostals tube drainage was done, and patient relieved
      immediately. Patient was kept in the hospital for 12 days and, and was discharged
      after intercostals tube removal. CONCLUSION: If a patient of miliary tuberculosis
      presents with shortness of breath diagnosis of pneumothorax should be considered.

PMID- 22362454
TI  - An inflamed trichilemmal (pilar) cyst: Not so simple?
AB  - CONTEXT: Trichilemmal (pilar) cysts are common skin lesions that often present on
      the scalps of mature men and women. These cysts often become inflamed when the
      wall of the cyst ruptures, but few reports have addressed the immunologic
      features of this process. CASE REPORT: A 22-year-old female presented with
      rapidly growing nodule on her left cheek, with evidence of acute inflammation.
      Skin tissue for hematoxylin and eosin examination, as well as for
      immunohistochemical analysis was taken and reviewed. As controls, we utilized two
      archival, non-inflamed trichilemmal cysts. Hematoxylin and eosin staining
      demonstrated classic features of an inflamed trichilemmal cyst. No cytologic
      atypia was noted, and no significant number of mitotic figures was identified.
      Immunohistochemistry stains revealed that several cell cycle/tumor
      suppressor/apoptotic markers, antigen presenting cell markers, metalloproteinases
      and T cell response markers were highly expressed inside and around the disrupted
      cyst. The control, non-inflamed cysts were negative for the same markers. CD1a
      was also appreciated within the epidermis, suprajacent to the inflamed cyst.
      CONCLUSIONS: Upregulation and/or downregulation of selected cell cycle regulator
      and/or tumor suppressor/apoptotic markers, as well as antigen presenting cells
      and some protein kinases could recruit and activate T lymphocytes and other
      inflammatory cells to the non-disrupted cyst for unknown reasons. The immune
      response may be involved in the initial cyst rupture, or induced by an unknown
      alteration in the cyst. Larger studies are needed to address these questions.

PMID- 22362455
TI  - Intra-atrial tumor thrombi secondary to hepatocellular carcinoma responding to
      chemotherapy.
AB  - CONTEXT: Hepatocellular carcinoma accounts for 1-2.5% of all cancer in America
      with extension to inferior vena cava and right atrium in 1-4% of the cases.
      Patients with advanced hepatocellular carcinoma invading the right heart are
      considered poor candidates for surgery. In the past, such patients had dismal
      prognosis due to complications like pulmonary embolism and sudden death. CASE
      REPORT: Our patient was admitted with worsening jaundice, abdominal pain and
      significant weight loss. Abdominal ultrasound, elevated alfa feto-protein levels
      and computerized tomography pointed to the diagnosis of hepatocellular carcinoma.
      Transthoracic echocardiography demonstrated two masses in the right atrium with
      the base of masses extending from inferior vena cava into right atrium. The
      patient was diagnosed to have stage IV heptaocellular carcinoma. This is
      associated with dismal prognosis. But after being started on sorafenib, the tumor
      regressed considerably and was barely discernable on echocardiography performed a
      month later. CONCLUSION: Though aggressive surgical resection is the best
      therapeutic approach for hepatocellular carcinoma, it may not always be possible
      and in such cases combination of different therapeutic approaches such as
      chemotherapeutic agents, radiotherapy and chemoembolization may improve survival.

PMID- 22362456
TI  - Chylous ascites.
AB  - CONTEXT: Chylous ascites is the accumulation of milky chyle in the peritoneal
      cavity. Chylous ascites has been reported after surgeries like abdominal aortic
      aneurysm repair, radical gastrectomy, duodenectomy, nephrectomy and Wilm's tumor
      resection. Our literature search did not reveal any reports of chylous ascites
      after a gastric ulcer resection. We report about an elderly woman with a rare
      complication of chylous ascites after an emergent surgery for a perforated
      gastric ulcer. CASE REPORT: A 70-year-old woman developed sudden respiratory
      distress on 5(th) post-operative day after an elective C3-C7 cervical discectomy
      and fusion. Her past medical history was significant for cervical spondylosis.
      The Computed Tomography (CT) scan of the chest revealed air under the diaphragm
      suspicious for hollow viscus perforation. She underwent an emergent surgery for
      drainage of hematoma in the neck along with an emergent laparotomy to repair a
      large perforated gastric ulcer distal to the gastro-esophageal junction. The
      patient had worsening of abdominal distention on 4(th) post-operative day. The CT
      scan of abdomen showed fluid collection in the abdomen. The abdominal drain
      revealed large amount of serous milky fluid at the rate of 1500 ml per day. The
      fluid analysis showed that the triglyceride level was 170 mg/dl and cholesterol
      level was 15 mg/dl. The fluid cultures did not grow any organism. She responded
      to treatment with octreotide and a diet of medium chain triglyceride oil.
      CONCLUSION: Any obstruction or damage to the lymphatic channels results in
      chylous ascites. Lymphomas, metastatic malignancies, and abdominal surgeries
      commonly cause chylous ascites. Ascitic fluid triglyceride level greater than 110
      mg/dl is diagnostic of chylous ascites. Chylous ascites is a rare complication of
      a peptic ulcer resection which can be managed effectively with octreotide.

PMID- 22362457
TI  - Epistaxis.

PMID- 22362458
TI  - Red Cross tries to negotiate a ceasefire in Syria.

PMID- 22362459
TI  - Government must listen to scientists as their ability to predict disasters
      improves.

PMID- 22362460
TI  - Agency is under fire for refusing to supply details of sudden deaths after first
      dose of multiple sclerosis drug.

PMID- 22362461
TI  - Colombia's response to healthcare crisis.

PMID- 22362463
TI  - Do carbenes have a "hidden" carbon(0) character? Revisiting the electronic
      structure of 2,2'-bipyridyl carbene.
AB  - Density functional calculations predict that 2,2'-bipyridyl carbenes have some
      degree of "hidden" carbon(0) character. This is supported by very high second
      proton affinity values and bond dissociation energies (BDEs) for the dissociation
      of one AuCl and one Ni(CO)(2) molecule from [(AuCl)(2)(2,2'-bipyridyl carbene)]
      and [{Ni(CO)(2)}(2)(2,2'-bipyridyl carbene)]. An Arduengo type carbene also
      showed significant BDE values for gem-dimetallation, thus indicating the possible
      existence of carbon(0) character. All of the dimetallated derivatives showed
      metallophilic interactions.

PMID- 22362462
TI  - Acetaminophen overdose in the Military Health System.
AB  - PURPOSE: We report the annual trend, distribution, and determinants of
      acetaminophen overdose using data from the Military Health System. We also assess
      the proportion of individuals with an acetaminophen overdose who received a
      prescription for any acetaminophen-containing medication prior to their event.
      METHODS: Diagnostic International Classification of Diseases, 9th revision (ICD
      9) codes from inpatient medical encounters were used to identify patients with
      acetaminophen overdose. We used Poisson regression to estimate adjusted
      prevalence ratios (aPRs) for associations between selected socio-demographic
      characteristics and acetaminophen overdose. Pharmacy records for individuals with
      an acetaminophen overdose were obtained to evaluate the proportion who received a
      prescription for any acetaminophen-containing medication prior to their overdose.
      RESULTS: Annual age-adjusted and sex-adjusted prevalence of acetaminophen
      overdose increased by 38.5% from 2004 to 2008. Acetaminophen overdose was
      significantly more common in female subjects than in male subjects (aPR = 3.24,
      95%CI = 2.97-3.55). Individuals aged 15-17 and 18-24 also were significantly more
      likely to have an overdose compared with those aged 45-64 (aPR = 6.06, 95%CI =
      5.25-7.00 and aPR = 4.58, 95%CI = 4.01-5.23, respectively). Among active duty
      service members, acetaminophen overdose was six times more common in junior
      enlisted service members than in officers (aPR = 6.06, 95%CI = 3.90-9.40). The
      proportion of individuals with an inpatient overdose who had any prescription for
      an acetaminophen-containing medication in the 365, 30, and 7 days before the
      overdose was 53.3%, 23.7%, and 16.3%, respectively. CONCLUSIONS: Identification
      of at-risk populations will aid the military in ongoing efforts to decrease
      medication misuse. Findings suggest a potential need for improved labeling of
      over-the-counter medications and medication safety education efforts for
      unintentional acetaminophen overdose and continued efforts to identify
      individuals at risk for intentional overdose. Published 2012. This article is a
      US Government work and is in the public domain in the USA.

PMID- 22362464
TI  - Thermodynamic stability explains the differential evolutionary dynamics of
      cytochrome b and COX I in mammals.
AB  - By using a combination of evolutionary and structural data from 231 species, we
      have addressed the relationship between evolution and structural features of
      cytochrome b and COX I, two mtDNA-encoded proteins. The interior of cytochrome b,
      in contrast to that of COX I, exhibits a remarkable tolerance to changes. The
      higher evolvability of cytochrome b contrasts with the lower rate of synonymous
      substitutions of its gene when compared to that of COX I, suggesting that the
      latter is subjected to a stronger purifying selection. We present evidences that
      the stability effect of mutations (DeltaDeltaG) may be behind these differential
      behaviour.

PMID- 22362465
TI  - Nucleotide composition of CO1 sequences in Chelicerata (Arthropoda): detecting
      new mitogenomic rearrangements.
AB  - Here we study the evolution of nucleotide composition in third codon-positions of
      CO1 sequences of Chelicerata, using a phylogenetic framework, based on 180 taxa
      and three markers (CO1, 18S, and 28S rRNA; 5,218 nt). The analyses of nucleotide
      composition were also extended to all CO1 sequences of Chelicerata found in
      GenBank (1,701 taxa). The results show that most species of Chelicerata have a
      positive strand bias in CO1, i.e., in favor of C nucleotides, including all
      Amblypygi, Palpigradi, Ricinulei, Solifugae, Uropygi, and Xiphosura. However,
      several taxa show a negative strand bias, i.e., in favor of G nucleotides: all
      Scorpiones, Opisthothelae spiders and several taxa within Acari, Opiliones,
      Pseudoscorpiones, and Pycnogonida. Several reversals of strand-specific bias can
      be attributed to either a rearrangement of the control region or an inversion of
      a fragment containing the CO1 gene. Key taxa for which sequencing of complete
      mitochondrial genomes will be necessary to determine the origin and nature of
      mtDNA rearrangements involved in the reversals are identified. Acari, Opiliones,
      Pseudoscorpiones, and Pycnogonida were found to show a strong variability in
      nucleotide composition. In addition, both mitochondrial and nuclear genomes have
      been affected by higher substitution rates in Acari and Pseudoscorpiones. The
      results therefore indicate that these two orders are more liable to fix mutations
      of all types, including base substitutions, indels, and genomic rearrangements.

PMID- 22362466
TI  - A review of knowledge in osteochondritis dissecans: 123 years of minimal
      evolution from Konig to the ROCK study group.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) was first described to provide an
      explanation for the nontraumatic development of loose bodies within a joint.
      Despite many reports on the subject, there remains no clear understanding of the
      etiology, natural history, or treatment. QUESTIONS/PURPOSES: This review was
      undertaken to delineate (1) the etiology of OCD; (2) the presentation and
      locations; (3) the most appropriate imaging modalities; and (4) the most
      effective treatment strategies. METHODS: We reviewed the English literature using
      a database compiled from a Medline search for "osteochondritis dissecans". We
      identified 1716 publications, 1246 of which were in English. After exclusions, we
      reviewed 748 articles and of these cited 85. The observations of each study were
      then synthesized into this report. RESULTS: There appears to be no consensus
      concerning the etiology of OCD lesions. The presentations and locations are
      variable, but the knee, ankle, and elbow are most commonly involved. Although
      plain film assessment is important in OCD, there appears to be a trend toward the
      use of MRI, but the preferred sequences are in evolution. We found no consensus
      on the treatment of these lesions, related in part to the lack of agreement of
      methods for assessing outcomes. CONCLUSIONS: Despite more than a century of
      study, we have made little advancement in our understanding of OCD. A study group
      has been formed to address this issue and actively seeks to answer these unknown
      issues regarding OCD.

PMID- 22362467
TI  - Subscapularis release in shoulder replacement determines structural muscular
      changes.
AB  - BACKGROUND: Osteotomy of the lesser tuberosity in shoulder arthroplasty allows
      bony healing of the subscapularis tendon but does not prevent fatty degeneration
      in its muscle. Occurrence or increase in fatty degeneration may depend on the
      surgical technique. QUESTIONS/PURPOSES: We (1) assessed fatty degeneration in the
      subscapularis muscle and its cross-sectional area after a C-block osteotomy of
      the lesser tuberosity with minimal mobilization of the subscapularis muscle, and
      (2) determined whether this technique had any adverse effect on function, fatty
      degeneration, and cross-sectional area of the subscapularis muscle. METHODS: We
      retrospectively examined 36 patients with shoulder replacements who had C-block
      osteotomies. Constant-Murley scores and clinical signs of subscapularis
      insufficiency were recorded. We radiographically assessed prosthetic placement.
      On CT scans, lesser tuberosity healing, fatty degeneration, and cross-sectional
      area of the subscapularis muscle were determined. The minimum followup was 13
      months (mean, 18 months; range, 13-33 months). RESULTS: The mean absolute
      Constant-Murley score was 71.2. Two patients had weakness of the subscapularis
      muscle without loss of active motion. All tuberosities healed anatomically. A
      normal glenohumeral relationship was found in all cases. Fatty degeneration was
      Grade 0 in 44%, Grade 1 in 39%, Grade 2 in 14%, and Grade 3 in 3%. The
      subscapularis muscular cross-sectional area decreased from 16.7 cm(2)
      preoperatively to 14.5 cm(2) postoperatively (13%). CONCLUSIONS: The C-block
      osteotomy with minimal dissection of the subscapularis is associated with a low
      incidence of fatty degeneration in the subscapularis muscle after shoulder
      arthroplasty although the muscular cross-sectional area of the subscapularis
      decreased. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22362468
TI  - German S3 guideline: anal abscess.
AB  - BACKGROUND: The incidence of anal abscess is relatively high, and the condition
      is most common in young men. METHODS: A systematic review of the literature was
      undertaken. RESULTS: This abscess usually originates in the proctodeal glands of
      the intersphincteric space. A distinction is made between subanodermal,
      intersphincteric, ischioanal, and supralevator abscesses. The patient history and
      clinical examination are diagnostically sufficient to establish the indication
      for surgery. Further examinations (endosonography, MRI) should be considered in
      recurrent abscesses or supralevator abscesses. The timing of the surgical
      intervention is primarily determined by the patient's symptoms, and acute abscess
      is generally an indication for emergency treatment. Anal abscesses are treated
      surgically. The type of access (transrectal or perianal) depends on the abscess
      location. The goal of surgery is thorough drainage of the focus of infection
      while preserving the sphincter muscles. The wound should be rinsed regularly
      (using tap water). The use of local antiseptics is associated with a risk of
      cytotoxicity. Antibiotic treatment is only necessary in exceptional cases.
      Intraoperative fistula exploration should be conducted with extreme care if at
      all; no requirement to detect fistula should be imposed. The risk of abscess
      recurrence or secondary fistula formation is low overall, but they can result
      from insufficient drainage. Primary fistulotomy should only be performed in case
      of superficial fistulas and by experienced surgeons. In case of unclear findings
      or high fistulas, repair should take place in a second procedure. CONCLUSION: In
      this clinical S3 guideline, instructions for diagnosis and treatment of anal
      abscess are described for the first time in Germany.

PMID- 22362469
TI  - Fibroblasts within concentrated collagen hydrogels favour chronic skin wound
      healing.
AB  - Apligraf((r)), a skin substitute currently used in skin chronic wound treatment,
      acts as a source of macromolecules and cytokines to promote wound healing. Normal
      collagen hydrogel (NCH), obtained from collagen at low concentration (0.66
      mg/ml), is the base of the dermal layer. Apligraf has several drawbacks, such as
      poor persistence of fibroblasts within the normal collagen hydrogel. In the
      present study we have evaluated concentrated collagen hydrogels at 5 mg/ml
      (CCH5s) as dermal substitutes for the treatment of skin chronic wounds. The
      effect of raised collagen concentration on hydrogel stability, cell growth,
      apoptosis and fibroblast phenotype was evaluated over 21 days in culture. In
      contrast to NCHs, CCH5s were more stable because no contraction was observed
      during the first week. CCH5 favoured cell proliferation and protected fibroblasts
      against apoptosis. At day 21, cell number assessed in CCH5 was around one
      million, i.e about 10 times higher than in NCH. Matrix metalloproteinases
      detection appeared lower in CCH5 than in NCH. In CCH5, fibroblasts exhibited a
      sustained collagen I gene expression for 14 days, while it was inhibited from day
      4 in NCH. Moreover, gene expression of KGF was constant in CCH5 and that of VEGFA
      increased from day 7. Taken together, our results demonstrate that concentrated
      collagen hydrogels at 5 mg/ml can be considered as new candidates for cell
      therapy in chronic skin wounds. They are stable, enhance cell viability and allow
      gene expression of matrix macromolecules and cytokines involved in re
      epithelialization or neovascularization.

PMID- 22362470
TI  - Distribution-free inference on contrasts of arbitrary summary measures of
      survival.
AB  - We present an approach for inference on contrasts of clinically meaningful
      functionals of a survivor distribution (e.g., restricted mean, quantiles) that
      can avoid strong parametric or semiparametric assumptions on the underlying
      structure of the data. In this multistage approach, we first use an adaptive
      predictive model to estimate conditional survival distributions based on
      covariates. We then estimate nonparametrically one or more functionals of
      survival from the covariate-specific survival curves and evaluated contrasts of
      those functionals. We find that the use of an adaptive nonparametric tree-based
      predictive model leads to minimal loss in precision when semiparametric
      assumptions hold and provides marked improvement in accuracy when those
      assumptions are invalid. Therefore, this work as a whole supports the use of
      survival summaries appropriate to a given medical application, whether that be,
      for example, the median or 75th percentile in some settings or perhaps a
      restricted mean in others. The approach is also compared with the Mayo R score
      for primary biliary cirrhosis prognosis.

PMID- 22362472
TI  - [Controversy. Dabigatran in the preventive treatment of embolic stroke: arguments
      in favour of its utilisation as a first-choice drug].

PMID- 22362471
TI  - Combined measurement of preoperative alpha-fetoprotein and des-gamma-carboxy
      prothrombin predicts recurrence after curative resection in patients with
      hepatitis-B-related hepatocellular carcinoma.
AB  - Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are widely used
      complementary tumor markers for hepatocellular carcinoma (HCC). In this study, we
      investigated whether preoperative AFP and DCP levels predict recurrence after
      curative resection in patients with hepatitis B virus (HBV)-related HCC. Records
      for 267 patients who were diagnosed with HBV-related HCC and who underwent
      curative resection for HCC were retrospectively reviewed. Patients were divided
      into two preoperative groups: pre-op I (AFP >= 20 ng/dL and DCP >= 40 mAU/mL) and
      pre-op II (AFP >= 20 ng/dL and DCP <40 mAU/mL; AFP <20 ng/dL and DCP >= 40
      mAU/mL; or AFP <20 ng/dL and DCP <40 mAU/mL). Among 267 patients, 102 (38.2%)
      patients were classified as pre-op I, whereas the other 165 (61.8%) belonged to
      pre-op II. During the post-resection follow-up [69.0 (3.0-136.0) months] period,
      154 (57.7%) patients developed recurrences [68 (66.7%) patients in pre-op I vs.
      86 (52.1%) in pre-op II, p = 0.029]. A multivariate analysis revealed that
      multiple tumors [hazard ratio (HR), 2.210; 95% confidence interval (CI), 1.185
      4.121] and pre-op I (HR: 1.890; 95% CI; 1.080-3.289) were significant predictors
      for recurrence. Disease-free survival (DFS) was significantly shorter in pre-op I
      compared to that in pre-op II (20.0 vs. 46.8 months, p = 0.006). Elevated
      preoperative AFP and DCP levels were associated with a higher recurrence rate and
      shorter DFS in patients with HBV-related HCC after curative resection. The
      combined measurement of preoperative AFP and DCP may be a prognostic factor for
      future recurrence.

PMID- 22362473
TI  - [Controversy. Dabigatran in the preventive treatment of embolic stroke: arguments
      against its utilisation as a first-choice drug].

PMID- 22362474
TI  - [Normalisation and validation of the Brief Neuropsychological Battery as the
      reference neuropsychological test in multiple sclerosis].
AB  - INTRODUCTION. The current batteries such as the Brief Repeatable Battery of
      Neuropsychological Tests (BRB-N) for evaluating cognitive decline in patients
      with multiple sclerosis are complex and time-consuming. AIM. To obtain normative
      values and validate a new battery. SUBJECTS AND METHODS. Four neuropsychological
      tests were finally included (episodic memory, the Symbol-Digit Modalities Test, a
      category fluency test, and the Paced Auditory Serial Addition Test). Normative
      values (overall and by age group) were derived by administering the battery to
      healthy subjects (5th percentile was the limit of normal). External validity was
      explored by comparison with the BRB-N. The new battery was also administered to a
      subsample after 4 weeks to assess reproducibility. RESULTS. To provide normative
      data, 1036 healthy subjects were recruited. The mean completion time was 18.5 +/-
      5.2 minutes. For the 229 subjects who were administered the new battery and the
      BRB-N, no statistically significant differences were found except for mean
      completion time (19 +/- 4 vs 25 +/- 5 minutes). In the reproducibility study,
      there were no significant differences except in the memory tests. CONCLUSION. The
      scores on the new battery and the BRB-N were strongly correlated although the
      shorter completion time and ease of administration could make the new battery
      preferable in clinical practice.

PMID- 22362475
TI  - [Perfusion computed tomography makes it possible to overcome important SITS-MOST
      exclusion criteria for the endovenous thrombolysis of cerebral infarction].
AB  - AIM. To study the frequency, safety and efficacy of perfusion computed tomography
      (PCT), through identification of brain tissue-at-risk, to guide intravenous
      thrombolysis in stroke patients with regulatory exclusion criteria (SITS-MOST and
      ECASS-3). PATIENTS AND METHODS. We studied consecutive acute non-lacunar ischemic
      stroke patients. After conventional CT was considered eligible, PCT was performed
      in the following circumstances: 4.5 to 6 h window, wake-up stroke or unknown time
      of onset; extent early infarct signs on CT; minor or severe stroke; seizures or
      loss of consciousness. Intravenous 0.9 mg/kg alteplase was indicated if: cerebral
      blood volume lesion covered < 1/3 of middle cerebral artery territory; mismatch >
      20% between mean transit time and cerebral blood volume maps existed; and
      informed consent. SITS-MOST safety-efficacy parameters were used as endpoint
      variables. RESULTS. Between May 2009-April 2010, 66 hyperacute ischemic stroke
      patients a priori not eligible for intravenous thrombolysis underwent PCT.
      Indications were: > 4.5 h in 18 patients, wake up stroke or unknown onset in 25,
      extent infarct signs in 6, seizures at onset in 11, and minor stroke (NIHSS < 4)
      in 6. Twenty-nine (44%) of them finally received intravenous thrombolysis.
      Symptomatic hemorrhagic transformation occurred in 2 (6.9%) patient and 18
      (62.1%) achieved a modified Rankin scale score equal or less than 2 on day 90.
      CONCLUSION. A high proportion of acute stroke patients with SITS-MOST and ECASS-3
      exclusion criteria can be safely and efficaciously treated with intravenous
      thrombolysis using a PCT selection protocol. However randomized control trials
      will be needed to confirm our results.

PMID- 22362476
TI  - [A study to compare independent groups of patients with episodic migraine who
      were treated preventively with flunarizine or nadolol].
AB  - INTRODUCTION. Flunarizine, with level of evidence A, and nadolol, with evidence
      level C, would be indicated as preventive treatment of migraine. Yet, no previous
      studies have been conducted to compare the effectiveness of the two drugs. AIM.
      To compare the effectiveness parameters in independent groups of patients treated
      preventively with one of the pharmaceuticals from the study, the same protocol
      being applied in both cases. PATIENTS AND METHODS. The subjects selected for the
      study were patients with episodic migraine (according to 2004 International
      Headache Society criteria) who had undergone preventive treatment for the first
      time, with flunarizine (5 mg/day) or nadolol (20-40 mg/day). The main
      effectiveness variables (reduction in the number of seizures at four months of
      treatment and responder rates) were analysed. RESULTS. The study included 227
      patients who intended to receive treatment: 155 with flunarizine (80.5% females;
      mean age: 38.3 +/- 12.1 years) and 72 with nadolol (63.8% females; mean age: 37.1
      +/- 12.0 years). The mean number of seizures prior to treatment was 6.09 +/- 2.6
      in the flunarizine group and 5.1 +/- 1.7 in the nadolol group (p = 0.0079); at
      four months of treatment it was 2.61 +/- 2.4 in the flunarizine group and 2.77 +/
      2.4 in the nadolol group (p = NS). Percentage of reduction of migraines: 55.2%
      with flunarizine and 50.4% with nadolol (p = NS). The responder rate was 69% with
      flunarizine and 67% with nadolol (p = NS). The excellent response rate (reduction
      in the number of seizures by 75% or more) was 52.2% with flunarizine and 36.1%
      with nadolol (p = 0.0077). Percentage of adverse side effects: 48.3% with
      flunarizine and 25% with nadolol (p = 0.0009). The satisfaction rate was similar
      in both groups, 68%. CONCLUSIONS. Both flunarizine and nadolol proved to be
      effective in the preventive treatment of episodic migraine. Flunarizine is used
      more often in our milieu and was less well tolerated.

PMID- 22362477
TI  - [Anterior circulation embolic stroke secondary to thrombotic occlusion of the
      brachiocephalic trunk: the usefulness of neurosonological studies].
AB  - INTRODUCTION. Atherosclerotic occlusion of the brachiocephalic trunk (CBT) is a
      rare clinical entity and its presentation in the form of arterio-arterial
      embolism is uncommon. Early identification of patients with CBT occlusion may
      have important therapeutic implications. CASE REPORT. A man aged 49 presents with
      sudden onset symptoms involving the territory of the right middle cerebral
      artery. Emergent transcranial doppler evaluation showed a flow pattern of
      proximal right M1 occlusion. After intravenous recombinant tissue plasminogen
      activator administration, partial recanalization of the vessel was found and the
      patient improved clinically. Cervical and transcranial duplex sonography
      demonstrated an occlusion in CBT, which was later confirmed on CT angiography and
      digital angiography of supraaortic vessels. After aorto-innominate bypass,
      pathological analysis confirmed the atherosclerotic origin. CONCLUSIONS. The most
      common clinical presentation of CBT occlusion are transient ischemic symptoms
      related to steal phenomenon in the vertebro-basilar territory. Symptoms of
      carotid circulation stroke usually result from arterio-arterial embolic
      mechanism. Early recognition is important for its therapeutic implications,
      therefore thrombolytic therapy should be indicated. Neurosonologic study allows
      rapid and reliable examination on hemodynamic status and the presence of distal
      embolic phenomena.

PMID- 22362478
TI  - [Diagnostic validity of attention deficit/hyperactivity disorder: from
      phenomenology to neurobiology (I)].
AB  - The diagnostic criteria for the attentional deficit hyperactivity disorder
      (ADHD), were defined by the American Psychiatric Association in the Diagnostic
      and Statistical Manual of Mental Disorders fourth version (DSM-IV) and World
      Health Organization in the ICD-10. The American Psychiatric Association used an
      internal validity analysis to select specific behavioral symptoms associated with
      the disorder and to build five cross-cultural criteria for its use in the
      categorical diagnosis. The DSM has been utilized for clinicians and researchers
      as a valid and stable approach since 1968. We did a systematic review of
      scientific literature in Spanish and English, aimed to identify the historical
      origin that supports ADHD as a psychiatric construct. This comprehensive review
      started exploring the concept of minimal brain dysfunction, hyper-activity,
      inattention, impulsivity since 1932 to 2011. This paper summarize all the DSM
      versions that include the definition of ADHD or its equivalent, and it point out
      the statistical and methodological approach implemented for defining ADHD as a
      valid epidemiological and psychometric construct. Finally the paper discusses
      some considerations and suggestions for the new versions of the manual.

PMID- 22362479
TI  - [Mild cognitive impairment: early detection and new perspectives].
AB  - INTRODUCTION. Along past years, interest in mild cognitive impairment (MCI)
      research and its early detection has been increased. Unlike first theories,
      international current proposals suggest that MCI is a syndrome characterized by
      an impairment in one or more cognitive functions without interfering in daily
      functional abilities and it is also accompanied by a concern because of the
      cognitive change. Although early MCI detection is usually made by cognitive
      screening tests, most of them do not seem to correctly detect MCI, but dementia.
      AIM. To expose an analysis of the cognitive screening tests more suitable for
      clinical MCI detection, according to current researches. DEVELOPMENT AND
      CONCLUSIONS. There are three kind of cognitive screening tests: general cognitive
      screening tests, specific cognitive screening tests and MCI-subtype cognitive
      screening test. We observe that most of the tests don't follow current MCI
      criteria. In this respect we propose to jointly apply tests, as well as the
      necessity of a carefully test choice to effectively detect MCI in clinical
      practice.

PMID- 22362480
TI  - [Post-traumatic syringomyelia in a young female].

PMID- 22362482
TI  - [Decompressive craniectomy for the treatment of intracranial hypertension after
      acute meningoencephalitis].

PMID- 22362483
TI  - [Some clarifications regarding botulinum toxin type A units. Reply].

PMID- 22362485
TI  - Cooperation of myocardin and Smad2 in inducing differentiation of mesenchymal
      stem cells into smooth muscle cells.
AB  - Several reports demonstrated that mesenchymal stem cells (MSCs) might
      differentiate into smooth muscle cells (SMCs) in vitro and in vivo. It has been
      shown that myocardin protein is a strong inducer of smooth muscle genes and MSCs
      can differentiate into SMCs in response to transforming growth factor-beta (TGF
      beta). However, the relationship or link between myocardin and TGF-beta3-induced
      MSC differentiation has not been fully elucidated. Here, we demonstrated that
      both myocardin and TGF-beta3 were able to induce differentiation of rat bone
      marrow-derived MSCs toward smooth-muscle-like cell types, as evidenced by
      increasing expression of SMC-specific genes. Of note, myocardin cooperated with
      Smad2 to synergistically activate SM22alpha promoter and significantly enhance
      the expression of SM22alpha. Report assays with site-direct mutation analysis of
      SM22alpha promoter demonstrated that myocardin and Smad2 coactivated SM22alpha
      promoter mainly depending on CArG box and less on smad binding elements (SBE)
      sites as well. These findings reveal the cooperation of myocardin and Smad2 in
      process of MSC differentiation into SMCs.

PMID- 22362486
TI  - Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in
      patients with schizophrenia and normal controls.
AB  - Studies suggest that a functional polymorphism of the brain-derived neurotrophic
      factor gene (BDNF Val66Met) may mediate hippocampal-dependent cognitive
      functions. A few studies have reported its role in cognitive deficits in
      schizophrenia including its association with peripheral BDNF levels as a mediator
      of these cognitive deficits. We assessed 657 schizophrenic inpatients and 445
      healthy controls on the repeatable battery for the assessment of
      neuropsychological status (RBANS), the presence of the BDNF Val66Met polymorphism
      and serum BDNF levels. We assessed patient psychopathology using the Positive and
      Negative Syndrome Scale. We showed that visuospatial/constructional abilities
      significantly differed by genotype but not genotype * diagnosis, and the Val
      allele was associated with better visuospatial/constructional performance in both
      schizophrenic patients and healthy controls. Attention performance showed a
      significant genotype by diagnosis effect. Met allele-associated attention
      impairment was specific to schizophrenic patients and not shown in healthy
      controls. In the patient group, partial correlation analysis showed a significant
      positive correlation between serum BDNF and the RBANS total score. Furthermore,
      the RBANS total score showed a statistically significant BDNF level * genotype
      interaction. We demonstrated an association between the BDNF Met variant and poor
      visuospatial/constructional performance. Furthermore, the BDNF Met variant may be
      specific to attentional decrements in schizophrenic patients. The association
      between decreased BDNF serum levels and cognitive impairment in schizophrenia is
      dependent on the BDNF Val66Met polymorphism.

PMID- 22362489
TI  - Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels
      tumor vascular density.
AB  - BACKGROUND: Visudyne(r)-mediated photodynamic therapy (PDT) at low drug/light
      conditions has shown to selectively enhance the uptake of liposomal doxorubicin
      in subpleural localized sarcoma tumors grown on rodent lungs without causing
      morphological alterations of the lung. The present experiments explore the impact
      of low-dose PDT on liposomal doxorubicin (LiporubicinTM) uptake to different
      tumor types grown on rodent lungs. MATERIAL AND METHODS: Three groups of Fischer
      rats underwent subpleural generation of sarcoma, mesothelioma, or adenocarcinoma
      tumors on the left lung. At least five animals of each group (sarcoma, n = 5;
      mesothelioma, n = 7; adenocarcinoma, n = 5) underwent intraoperative low-dose (10
      J/cm(2) at 35 mW/cm(2) ) PDT with 0.0625 mg/kg Visudyne(r) of the tumor and the
      lower lobe. This was followed by intravenous (IV) administration of 400 ug
      LiporubicinTM. After a circulation time of 60 min, the tumor-bearing lung was
      processed for HPLC analyses. At least five animals per group underwent the same
      procedure but without PDT (sarcoma, n = 5; mesothelioma, n = 5; adenocarcinoma, n
      = 6). Five untreated animals per group underwent CD31 immunostaining of their
      tumors with histomorphometrical assessment of the tumor vascularization. RESULTS:
      Low-dose PDT significantly enhanced LiporubicinTM uptake to all tumor types
      (sarcoma, P = 0.0007; mesothelioma, P = 0.001; adenocarcinoma, P = 0.02) but not
      to normal lung tissue compared to IV drug administration alone. PDT led to a
      significantly increased ratio of tumor to lung tissue drug uptake for all three
      tumor types (P < 0.05). However, the tumor drug uptake varied between tumor types
      and paralleled tumor vascular density. The vascular density was significantly
      higher in sarcoma than in adenocarcinoma (P < 0.001) and mesothelioma (P <
      0.001), whereas there was no significant difference between adenocarcinoma and
      mesothelioma. CONCLUSION: Low-dose Visudyne(r)-mediated PDT selectively enhances
      the uptake of systemically administered liposomal doxorubicin in tumors without
      affecting the drug uptake to normal lung. However, drug uptake varied
      significantly between tumor types and paralleled tumor vascular density.

PMID- 22362490
TI  - Chronic idiopathic urticaria, psychological co-morbidity and posttraumatic
      stress: the impact of alexithymia and repression.
AB  - The objective of this study was to investigate the interrelationship between
      chronic idiopathic urticaria (CIU), psychological co-morbidity, posttraumatic
      stress, repression and alexithymia. 89 participants with CIU and 105 without CIU
      responded to an online questionnaire. Both groups completed the general health
      questionnaire-12, the perceived stress scale, the posttraumatic stress diagnostic
      scale and the Toronto alexithymia scale-20 and were categorised into four defence
      mechanism groups (repressive, defensive, high-anxious, low-anxious). CIU
      participants also completed the Skindex-17 and a self-report severity measure.
      CIU participants reported higher levels of alexithymia than the control group and
      their defence mechanism was most likely to be categorised as defensive, with
      conscious self-image management reported alongside high manifest anxiety. Partial
      least squares analysis revealed significant paths between posttraumatic stress
      and CIU severity and psychological co-morbidity. Posttraumatic stress was
      associated with alexithymia and type of defence mechanism. Only being in the high
      anxious group partially mediated the relationship between posttraumatic stress
      and CIU severity. In conclusion, there is evidence for a relationship between CIU
      and trauma. The severity of posttraumatic symptoms varies depending upon
      alexithymic traits and defence mechanisms used. Disease severity and
      psychological co-morbidity are differentially influenced by the relationships
      between trauma, alexithymic traits and defence mechanisms.

PMID- 22362491
TI  - Stereoselective synthesis of hydroxy stilbenoids and styrenes by atom-efficient
      olefination with thiophthalides.
AB  - The synthesis of stilbenoids and styryl carboxylic acids is accomplished with
      high E-stereoselectivity by olefination of aldehydes with thiophthalides under
      basic conditions. The olefination is highly atom-efficient as it only loses
      elemental sulfur during the reaction. This olefination, in conjunction with retro
      Kolbe-Schmitt reaction, allows facile synthesis of E-hydroxystilbenoids with
      minimal employment of protecting groups. This study also discloses two important
      findings: formation of i) 4-methylsulfanyl isocoumarins and ii) an 2
      arylindenone.

PMID- 22362492
TI  - Elongated thrombin binding aptamer: a G-quadruplex cation-sensitive
      conformational switch.
AB  - Aptamer-based biosensors offer promising perspectives for high performance,
      specific detection of proteins. The thrombin binding aptamer (TBA) is a G
      quadruplex-forming DNA sequence, which is frequently elongated at one end to
      increase its analytical performances in a biosensor configuration. Herein, we
      investigate how the elongation of TBA at its 5' end affects its structure and
      stability. Circular dichroism spectroscopy shows that TBA folds in an
      antiparallel G-quadruplex conformation with all studied cations (Ba(2+), Ca(2+),
      K(+), Mg(2+), Na(+), NH(4)(+), Sr(2+) and the [Ru(NH(3))(6)](2+/3+) redox marker)
      whereas other structures are adopted by the elongated aptamers in the presence of
      some of these cations. The stability of each structure is evaluated on the basis
      of UV spectroscopy melting curves. Thermal difference spectra confirm the
      quadruplex character of all conformations. The elongated sequences can adopt a
      parallel or an antiparallel structure, depending on the nature of the cation;
      this can potentially confer an ion-sensitive switch behavior. This switch
      property is demonstrated with the frequently employed redox complex
      [Ru(NH(3))(6)](3+), which induces the parallel conformation at very low
      concentrations (10 equiv per strand). The addition of large amounts of K(+)
      reverts the conformation to the antiparallel form, and opens interesting
      perspectives for electrochemical biosensing or redox-active responsive devices.

PMID- 22362493
TI  - Community pharmacists' adoption of medicines reclassified from prescription-only
      status: a systematic review of factors associated with decision making.
AB  - PURPOSE: Subsequent to reclassification of legal status, more than 90
      prescription-only medicines have become available in the UK alone without a
      prescription. Similar changes are taking place internationally. The aim was to
      systematically review studies reporting factors associated with community
      pharmacists' decision making around adoption of these reclassified medicines into
      practice. METHOD: A systematic review of English language peer-reviewed published
      literature from 1990 to 2010 was conducted. Literature was identified through
      MEDLINE, EMBASE, IPA, CINAHL, BSP, Cochrane Library and PsychINFO databases and
      other sources including key conference abstracts. RESULTS: A total of 38 studies
      were included. Twenty-eight factors associated with pharmacists' decision making
      were identified. Medicine safety was consistently shown to be one of the key
      factors; however, the importance of evidence base and financial benefits of
      reclassification were less obvious. A paucity of high-quality studies limits
      generalisation of findings. CONCLUSIONS: Patient safety appears to be the key to
      pharmacists' decision making. However, the study quality limitations indicate the
      need for further robust research. The 28 factors identified in this systematic
      review from international literature can aid rigorous research instrument
      development for future evaluations.

PMID- 22362494
TI  - Molecular analysis of age and sex-related gene expression in meniscal tears with
      and without a concomitant anterior cruciate ligament tear.
AB  - BACKGROUND: The meniscus plays critical roles in the knee, contributing to load
      transmission, shock absorption, and joint stability. Little is known about gene
      expression in meniscal tears, particularly in relation to injury pattern and
      patient age and sex. The purpose of this study was to test the hypothesis that
      gene expression in meniscal tears varies depending on patient age and sex and
      whether the anterior cruciate ligament (ACL) is also torn. METHODS: Meniscal
      tissue from twenty-eight patients with an isolated meniscal tear or a meniscal
      tear with a concomitant ACL tear was collected at the time of clinically
      indicated partial meniscectomy. Messenger RNA (mRNA) expression was examined by
      quantitative real-time polymerase chain reaction for molecular markers of
      osteoarthritis including proinflammatory cytokines (interleukin [IL]-1alpha, IL
      1beta, IL-6, and tumor necrosis factor-alpha [TNFalpha]), chemokines (IL-8, CCL3,
      CCL3L1, CXCL1, CXCL3, CXCL6, and CCL20), aggrecanases (ADAMTS-4 [a disintegrin
      and metalloproteinase with thrombospondin type-4 motifs] and ADAMTS-5), matrix
      metalloproteinases (MMP-1, MMP-3, MMP-9, and MMP-13), transcription factors
      (NFkappaB2 [nuclear factor kappa B2], NFkappaBIA [NF-kappa B inhibitor alpha],
      and IkappaBA [inhibitor of kappa B alpha]), and matrix components (bone
      morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and
      aggrecan). RESULTS: Expression of IL-1beta (p = 0.02), ADAMTS-5 (p = 0.001), MMP
      1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NFkappaB2 (p = 0.01) was
      significantly higher in patients with a meniscal tear who were under the age of
      forty years than it was in those over the age of forty years. Similarly, the
      expression of ADAMTS-4 (p = 0.002), ADAMTS-5 (p = 0.02), MMP-1 (p = 0.02), and
      MMP-13 (p = 0.0002) was higher in patients with a meniscal tear and an ACL tear
      who were under the age of forty years than it was in those over forty years. In
      patients with a meniscal tear and an ACL tear, the expression of IL-1beta (p =
      0.01), TNFalpha (p = 0.02), MMP-13 (p = 0.004), CCL3 (p = 0.03), and CCL3L1 (p =
      0.03) was significantly higher, while that of aggrecan (p = 0.03) was lower, than
      that in patients with a meniscal tear alone. The only sex-based difference in
      gene expression was higher levels of CCL3L1 in female patients (p < 0.05) of all
      ages with combined injuries. CONCLUSIONS AND CLINICAL RELEVANCE: These findings
      suggest clinically relevant differences in the response of the knee to meniscal
      tears on the basis of patient age and sex. Elevated expression levels of
      arthritis-related markers indicate an increased catabolic response in patients
      under forty years old. Higher expression of catabolic markers in patients with
      meniscal and ACL tears suggests this combined injury pattern is more likely to
      lead to the development of osteoarthritis. Catabolic activity in meniscal tissue
      may predict patients who are at risk for progression of osteoarthritis following
      partial meniscectomy.

PMID- 22362495
TI  - The meniscus--a key to unfolding the mystery of osteoarthritis: commentary on an
      article by Robert H. Brophy, MD, et al.: "Molecular analysis of age and sex
      related gene expression in meniscal tears with and without a concomitant anterior
      cruciate ligament tear".

PMID- 22362497
TI  - An eleven-vertex metallaborane with tetracapped pentagonal bipyramidal geometry.
AB  - A metallaborane of novel structure,
      [(Cp*Mo)(2)B(3)H(3)Se(2){Fe(CO)(2)}(2){Fe(CO)(3)}(2)] (2; Cp* = eta(5)
      C(5)Me(5)), with tetracapped pentagonal bipyramidal geometry, isolated from the
      reaction of [(Cp*Mo)(2)B(4)H(4)Se(2)], 1 with [Fe(2)(CO)(9)]; the title compound
      exhibit an 11-vertex closo-cage geometry, having eight skeletal electron pairs
      (sep) and 98 valence electrons, appropriate for its geometric structure.

PMID- 22362498
TI  - Type III polyketide synthases in natural product biosynthesis.
AB  - Polyketides represent an important class of biologically active and structurally
      diverse compounds in nature. They are synthesized from acyl-coenzyme A substrates
      by polyketide synthases (PKSs). PKSs are classified into three groups: types I,
      II, and III. This article introduces recent studies on type III PKSs identified
      from plants, bacteria, and fungi, and describes the catalytic functions of these
      enzymes in detail. Plant type III PKSs have been widely studied, as exemplified
      by chalcone synthase, which plays an important role in the synthesis of plant
      metabolites. Bacterial type III PKSs fall into five groups, many of which were
      identified from Streptomyces, a genus that has been well known for its production
      of bioactive molecules and genetic alterability. Although it was believed that
      type III PKSs exist exclusively in plants and bacteria, recent fungal genome
      sequencing projects and biochemical studies revealed the presence of type III
      PKSs in filamentous fungi, which provides a new chance to study fungal secondary
      metabolism and synthesize "unnatural" natural products. Type III PKSs have been
      used for the biosynthesis of novel molecules through precursor-directed and
      structure-based mutagenesis approaches.

PMID- 22362499
TI  - Antibacterial and anticancer activity of epsilon-poly-L-lysine (epsilon-PL)
      produced by a marine Bacillus subtilis sp.
AB  - A marine Bacillus subtilis SDNS was isolated from sea water in Alexandria and
      identified using 16S rDNA sequence analysis. The bacterium produced a compound
      active against a number of gram negativeve bacteria. Moreover, the anticancer
      activity of this bacterium was tested against three different human cell lines
      (Hela S3, HepG2 and CaCo). The highest inhibition activity was recorded against
      Hela S3 cell line (77.2%), while almost no activity was recorded towards CaCo
      cell line. HPLC and TLC analyses supported evidence that Bacillus subtilis SDNS
      product is epsilon-poly-L-lysine. To achieve maximum production, Plackett-Burman
      experimental design was applied. A 1.5 fold increase was observed when Bacillus
      subtilis SDNS was grown in optimized medium composed of g/l: (NH(4))(2) SO(4),
      15; K(2)HPO(4), 0.3; KH(2)PO(4), 2; MgSO(4) . 7 H(2)O, 1; ZnSO(4) . 7 H(2)O, 0;
      FeSO(4) . 7 H(2)O, 0.03; glucose, 25; yeast extract, 1, pH 6.8. Under optimized
      culture condition, a product value of 76.3 mg/l could be obtained. According to
      available literature, this is the first announcement for the production of
      epsilon-poly-L-lysine (epsilon-PL) by a member of genus Bacillus.

PMID- 22362500
TI  - Student perceptions of an upper-level, undergraduate human anatomy laboratory
      course without cadavers.
AB  - Several programs in health professional education require or are considering
      requiring upper-level human anatomy as prerequisite for their applicants.
      Undergraduate students are confronted with few institutions offering such a
      course, in part because of the expense and logistical issues associated with a
      cadaver-based human anatomy course. This study describes the development of and
      student reactions to an upper-level human anatomy laboratory course for
      undergraduate students that used a regional approach and contemporary,
      alternative teaching methods to a cadaver-based course. The alternative pedagogy
      to deliver the curriculum included use of commercially available, three
      dimensional anatomical virtual dissection software, anatomical models coupled
      with a learning management system to offer Web-based learning, and a new
      laboratory manual with collaborative exercises designed to develop the student's
      anatomical skills and collaborative team skills. A Likert-scale survey with open
      ended questions was used to ascertain student perceptions of the course and its
      various aspects. Students perceived that the noncadaver-based, upper-level human
      anatomy course with an engaging, regional approach is highly valuable in their
      learning of anatomy. anatomy.

PMID- 22362501
TI  - Intimal sarcoma of the pulmonary artery with unusual findings: a case report.

PMID- 22362503
TI  - Direct thrombin inhibitor (DTI) vs. aspirin in primary total hip and knee
      replacement using wound ooze as the primary outcome measure. A prospective cohort
      study.
AB  - The latest NICE guidance dictates that all patients undergoing lower-limb
      arthroplasty should be prescribed potent venous thromboembolic (VTE) prophylaxis.
      However, use of potent anti-thrombotics is likely to lead to increased post
      operative wound ooze. Postoperative wound ooze is associated with increased risk
      of infection. This study used a prospective, consecutive, multi-surgeon sample of
      110 patients undergoing primary total hip replacement (THR) and total knee
      replacement (TKR) prescribed either direct thrombin inhibitor (DTI) (n=51, 26
      males: 25 females, age 69 +/-18) or aspirin (n=59, 25 males: 34 females, age 69
      +/- 19). Hospital stay, body mass index (BMI), wound length and patient
      demographics were documented along with a daily assessment of wound ooze. The use
      of DTI's was associated with a significant increase in mean days to dryness in
      both THR (6.2 +/- 0.98, 95% C.I. 5.2-7.1) and TKR (6.6 +/- 1.89, 95% C.I. 4.7
      8.5) compared to aspirin in THR (3.0 +/- 1.03, 95% C.I 1.9-4.0) and TKR (3.4 +/-
      1.21, 95% C.I 2.2-4.6) with p-values of <0.0001 and 0.0024 for THR and TKR
      respectively. Age, gender and wound length were not found to be significant
      confounding variables. DTI's proven benefit in lowering venous thromboembolism
      when compared with aspirin needs to be balanced with their increased cost and
      increased duration of wound ooze.

PMID- 22362502
TI  - Severe autonomic failure in moderate to severe aortic stenosis: prevalence and
      association with hemodynamics and biomarkers.
AB  - BACKGROUND: Severe autonomic failure (SAF) refers to combined abnormalities in
      reflex and tonic autonomic function. SAF indicates increased risk of death in
      post-infarction and heart failure patients, but has not been studied in aortic
      stenosis (AS). Here, we investigated SAF in patients with AS and tested its
      correlation with hemodynamic and biochemical markers. METHODS: We prospectively
      enrolled 174 patients with moderate to severe AS in sinus rhythm (age 76 +/- 9
      years; mean aortic valve area 0.9 +/- 0.3 cm(2)). Heart rate turbulence (as
      marker of autonomic reflex activity) and deceleration capacity (as marker of
      autonomic tonic activity) were calculated from 24-h Holter recordings. According
      to the previously published technology, SAF was considered present if both
      factors were abnormal. RESULTS: 44 (25.3%) of the 174 patients had signs of SAF.
      Patients with SAF had lower left ventricular ejection fraction (LVEF: 48.1 vs.
      54.8%; p = 0.002), lower mean aortic gradients (28 vs. 34 mmHg, p = 0.019),
      higher systolic pulmonary artery pressures (46.8 vs. 40.9 mmHg, p = 0.028),
      higher levels of brain natriuretic peptide (905 vs. 407 ng/l; p = 0.003) and
      higher levels of high sensitive troponin I (0.65 vs. 0.24 MUg/l; p = 0.013).
      Impaired LVEF (<=50%) was the only independent factor associated with SAF, but
      only explained autonomic abnormalities in less than half of the patients.
      CONCLUSIONS: In patients with moderate to severe AS prevalence of SAF is high.
      SAF correlates with hemodynamic and biochemical markers indicating increased
      risk. Future studies should evaluate the prognostic value of SAF in patients with
      AS.

PMID- 22362504
TI  - Hospital cost of treating early dislocation following hip arthroplasty.
AB  - Dislocation is a frequent and costly complication of hip arthroplasty. The
      purpose of this study was to assess the financial impact on the treating
      institution of this complication in patients with primary hemiarthroplasty (HA),
      total hip arthroplasty (THA) and revision surgery (RTHA). Between October 2001
      and August 2009, 2014 consecutive hip arthroplasties were performed at our
      institution, of which 87 (18 HA, 44 THA and 25 RTHA) dislocated within 6 weeks of
      the primary operation. The average cost of treating implant dislocation by closed
      reduction, open reduction or revision was assessed and expressed as a percentage
      cost increase compared to an uncomplicated procedure. Of the 87 dislocated
      implants all needed one or more closed reductions and 52 eventually required
      revision surgery. An early dislocation increased the cost of HA, THA and RTHA by
      472%, 342% and 352%, respectively.

PMID- 22362505
TI  - Risk factors for heterotopic ossification in primary total hip arthroplasty.
AB  - Heterotopic ossification (HO) is a recognised complication of total hip
      arthroplasty (THA). This study aims to correlate demographics, surgical approach
      and type of arthroplasty to the incidence of HO in an attempt to quantify patient
      risk. A total of 920 primary THAs in 893 patients were performed between 2006 and
      2008 in a single arthroplasty centre. Radiographic evaluation was conducted and
      all cases of HO were classified using the Brooker classification. Age, sex,
      arthroplasty type and surgical approach were all considered as variables.
      Arthroplasty type was classified into four groups; total cemented (TC), total
      uncemented (TU), hybrid (H) and reverse hybrid (RH). Two-level logistic
      regression analysis was conducted. The overall incidence of HO was 24%. Male sex
      [OR=3.57, 95% CI (1.79-7.10); p=0.001], lateral approach [OR=2.47, (95% CI 1.23
      4.95); p=0.001] and total cemented implants [OR=3.14, (95%CI 1.37-7.23); p=0.007]
      were significantly associated with HO. The intra-class correlation coefficient
      was 0.52 [95% CI (0.21, 0.81); p=0.004], demonstrating that patients with
      previous HO to one THA were very likely to suffer HO in subsequent THA. The
      results demonstrate very large effects for sex, surgical approach, and implant
      type on HO incidence. This raises a three arm hypotheses that reaming of the
      femoral canal for the insertion of cemented implants contaminates the surgical
      field with bone marrow increasing the risk of HO, whereas modern cementless
      implants generally employ impaction broaching. In addition surgical insult to the
      hip abductors during exposure, particularly in males due to higher muscle mass,
      may also predispose to HO.

PMID- 22362506
TI  - Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid
      cells following whole-body irradiation is CCL2 dependent.
AB  - Previous studies have shown that following whole-body irradiation bone marrow
      (BM)-derived cells can migrate into the central nervous system, including the
      retina, to give rise to microglia-like cells. The detailed mechanism, however,
      remains elusive. We show in this study that a single-dose whole-body gamma-ray
      irradiation (8 Gy) induced subclinical damage (i.e., DNA damage) in the neuronal
      retina, which is accompanied by a low-grade chronic inflammation, para
      inflammation, characterized by upregulated expression of chemokines (CCL2,
      CXCL12, and CX3CL1) and complement components (C4 and CFH), and microglial
      activation. The upregulation of chemokines CCL2 and CXCL12 and complement C4
      lasted for more than 160 days, whereas the expression of CX3CL1 and CFH was
      upregulated for 2 weeks. Both resident microglia and BM-derived phagocytes
      displayed mild activation in the neuronal retina following irradiation. When BM
      cells from CX3CR1(gfp/+) mice or CX3CR1(gfp/gfp) mice were transplanted to wild
      type C57BL/6 mice, more than 90% of resident CD11b(+) cells were replaced by
      donor-derived GFP(+) cells after 6 months. However, when transplanting
      CX3CR1(gfp/+) BM cells into CCL2-deficient mice, only 20% of retinal CD11b(+)
      cells were replaced by donor-derived cells at 6 month. Our results suggest that
      the neuronal retina suffers from a chronic stress following whole-body
      irradiation, and a para-inflammatory response is initiated, presumably to rectify
      the insults and maintain homeostasis. The recruitment of BM-derived myeloid cells
      is a part of the para-inflammatory response and is CCL2 but not CX3CL1 dependent.

PMID- 22362508
TI  - Immunohistochemical localization of the angiotensin-(1-7) receptor Mas in the
      murine forebrain.
AB  - Apart from the well-known biologically active angiotensin II, other biologically
      active angiotensins have been discovered, including angiotensin IV and
      angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto
      oncogene encodes a receptor that is essential for angiotensin-(1-7) signaling.
      Angiotensin-(1-7) is not only expressed in the periphery but also within the
      brain. Based on that, we examined the distribution of Mas within the murine
      brain, using an antibody directed against the 3(rd) cytoplasmic loop of the
      receptor protein. Strongest Mas protein expression was detected in the dentate
      gyrus of the hippocampus and within the piriform cortex. However, Mas protein
      expression is not restricted to these areas, since Mas immunopositive neurons
      were also seen in different parts of the cortex, hippocampus, amygdala, basal
      ganglia, thalamus and hypothalamus. Based on the expression of Mas protein in the
      cortex and the limbic system, angiotensin-(1-7) signaling may play a role in
      synaptic plasticity, learning, memory and emotion, as has been described for
      angiotensin II and IV.

PMID- 22362509
TI  - Quantifying vapor drift of dicamba herbicides applied to soybean.
AB  - Recent advances in biotechnology have produced cultivars of corn, soybean, and
      cotton resistant to the synthetic-auxin herbicide dicamba. This technology will
      allow dicamba herbicides to be applied in new crops, at new periods in the
      growing season, and over greatly expanded areas, including postemergence
      applications in soybean. From past and current use in corn and small grains,
      dicamba vapor drift and subsequent crop injury to sensitive broadleaf crops has
      been a frequent problem. In the present study, the authors measured dicamba vapor
      drift in the field from postemergence applications to soybean using greenhouse
      grown soybean as a bioassay system. They found that when the volatile
      dimethylamine formulation is applied, vapor drift could be detected at mean
      concentrations of 0.56 g acid equivalent dicamba/ha (0.1% of the applied rate) at
      21 m away from a treated 18.3 * 18.3 m plot. Applying the diglycolamine
      formulation of dicamba reduced vapor drift by 94.0%. With the dimethylamine
      formulation, the extent and severity of vapor drift was significantly correlated
      with air temperature, indicating elevated risks if dimethylamine dicamba is
      applied early to midsummer in many growing regions. Additional research is needed
      to more fully understand the effects of vapor drift exposures to nontarget crops
      and wild plants.

PMID- 22362507
TI  - Role of the lesion scar in the response to damage and repair of the central
      nervous system.
AB  - Traumatic damage to the central nervous system (CNS) destroys the blood-brain
      barrier (BBB) and provokes the invasion of hematogenous cells into the neural
      tissue. Invading leukocytes, macrophages and lymphocytes secrete various
      cytokines that induce an inflammatory reaction in the injured CNS and result in
      local neural degeneration, formation of a cystic cavity and activation of glial
      cells around the lesion site. As a consequence of these processes, two types of
      scarring tissue are formed in the lesion site. One is a glial scar that consists
      in reactive astrocytes, reactive microglia and glial precursor cells. The other
      is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from
      adjacent meningeal and perivascular cells. At the interface, the reactive
      astrocytes and the fibroblasts interact to form an organized tissue, the glia
      limitans. The astrocytic reaction has a protective role by reconstituting the
      BBB, preventing neuronal degeneration and limiting the spread of damage. While
      much attention has been paid to the inhibitory effects of the astrocytic
      component of the scars on axon regeneration, this review will cover a number of
      recent studies in which manipulations of the fibroblastic component of the scar
      by reagents, such as blockers of collagen synthesis have been found to be
      beneficial for axon regeneration. To what extent these changes in the fibroblasts
      act via subsequent downstream actions on the astrocytes remains for future
      investigation.

PMID- 22362510
TI  - Toxicity of profenofos to the springtail, Folsomia candida, and ammonia-oxidizers
      in two agricultural soils.
AB  - Extensive use of organophosphorus insecticide profenofos (PFF) for agricultural
      and house-hold purposes has led to serious environmental pollution, with
      potential risk to organisms in the ecosystem. This study examined the toxicity of
      PFF to the soil springtail Folsomia candida and ammonia-oxidizers through a
      series of toxicity tests conducted on two agricultural soils. It was found that
      the survival, reproduction, hsp70 gene expression of F. candida and the soil
      potential nitrification rate (PNR) were sensitive to the PFF, whereas no apparent
      change was observed in the abundance of ammonia-oxidizers. The reproduction of F.
      candida was the most sensitive endpoint (mean 0.10 mg/kg of EC(50) value) for
      PFF, although the test was more time-consuming. The results of the acute toxicity
      tests suggested that the survival of F. candida could be considered as the most
      suitable bioindicator for fast screening of PFF toxicity because of its fast and
      easy test procedure. In addition, the hsp70 gene expression in F. candida and the
      PNR could be used as important parameters for assessment of PFF toxicity. The
      threshold concentration based on the obtained endpoints differed in the two
      soils, and consequently the soil property should be considered in toxicity
      assessments of contaminated soils.

PMID- 22362511
TI  - Hepatic proteome changes in Solea senegalensis exposed to contaminated estuarine
      sediments: a laboratory and in situ survey.
AB  - Assessing toxicity of contaminated estuarine sediments poses a challenge to
      ecotoxicologists due to the complex geochemical nature of sediments and to the
      combination of multiple classes of toxicants. Juvenile Senegalese soles were
      exposed for 14 days in the laboratory and in situ (field) to sediments from three
      sites (a reference plus two contaminated) of a Portuguese estuary. Sediment
      characterization confirmed the combination of metals, polycyclic aromatic
      hydrocarbons and organochlorines in the two contaminated sediments. Changes in
      liver cytosolic protein regulation patterns were determined by a combination of
      two-dimensional electrophoresis with de novo sequencing by tandem mass
      spectrometry. From the forty-one cytosolic proteins found to be deregulated,
      nineteen were able to be identified, taking part in multiple cellular processes
      such as anti-oxidative defence, energy production, proteolysis and contaminant
      catabolism (especially oxidoreductase enzymes). Besides a clear distinction
      between animals exposed to the reference and contaminated sediments, differences
      were also observed between laboratory- and in situ-tested fish. Soles exposed in
      the laboratory to the contaminated sediments failed to induce, or even markedly
      down-regulated, many proteins, with the exception of a peroxiredoxin (an anti
      oxidant enzyme) and a few others, when compared to reference fish. In situ
      exposure to the contaminated sediments revealed significant up-regulation of
      basal metabolism-related enzymes, comparatively to the reference condition. Down
      regulation of basal metabolism enzymes, related to energy production and gene
      transcription, in fish exposed in the laboratory to the contaminated sediments,
      may be linked to sediment-bound contaminants and likely compromised the
      organisms' ability to deploy adequate responses against insult.

PMID- 22362512
TI  - Failure of intertrochanteric nailing due to distal nail jamming.
AB  - Nail impingement against the anterior femoral cortex during nail insertion, or
      anterior cortex penetration, has been described in the literature as a worrying
      complication. We describe a previously unreported surgical failure due to a
      compromised dynamic distal locking caused by distal jamming of the nail. An 80
      year-old male suffered a closed right intertrochanteric femoral fracture. Due to
      the presence of a long medial fragment, a 240 mm long titanium trochanteric nail
      was chosen to stabilize the fracture. Dynamic distal locking was performed by
      placing the distal screw at the inferior rim of the elliptical locking hole to
      allow compression of the fracture site during weight-bearing. Six-month X-ray
      follow-up revealed a broken nail and nonunion of the fracture due to failed
      dynamization of the distal locking screw. The nail was removed and replaced by a
      total arthroplasty. Due to the femoral anterior bow of the shaft, anterior
      cortical impingement of the distal tip of a nail may result in the failure of the
      nail to slide within the diaphyseal canal when using a medium-length nail
      preventing compression of the fracture. Dynamic distal locking can be ineffective
      if the ability of the distal nail to slide within the diaphyseal canal is
      hindered. This type of scenario can represent an opportunity for anterior nail
      impingement. Distal jamming of the nail can thus compromise dynamic compression
      at the fracture site during loading, thus inducing nonunion of the fracture, and
      leading to breakage of the osteosynthesis device. For these reasons, caution is
      recommended when using medium-length trochanteric nails for unstable trochanteric
      fractures.

PMID- 22362513
TI  - Comparison of drug-eluting stents with bare metal stents in patients with ST
      segment elevation myocardial infarction.
AB  - AIMS: To evaluate safety and effectiveness of early generation drug-eluting
      stents (DES) compared with bare-metal stents (BMS) in patients with ST-segment
      elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (PCI), and to determine whether benefits and risks vary over time.
      METHODS AND RESULTS: We performed a meta-analysis of 15 randomized controlled
      trials enrolling a total of 7867 patients comparing first-generation FDA-approved
      DES with BMS in patients with STEMI. Random effect models were used to assess
      differences in outcomes between DES and BMS among different time periods with
      regard to the pre-specified primary outcomes stent thrombosis (ST) and target
      vessel revascularization (TVR). The overall risk of definite ST was similar for
      DES and BMS [risk ratio (RR) = 1.08, 95% CI 0.82-1.43]. However, there were time
      dependent effects, with a RR of 0.80 during the first year (95% CI 0.58-1.12) and
      2.10 during subsequent years (95% CI 1.20-3.69), with a positive test for
      interaction between RR of ST and time (P for interaction = 0.009). Results were
      similar for definite or probable ST (P for interaction = 0.015). In the overall
      analysis, TVR was performed less frequently in patients with DES when compared
      with BMS (RR 0.51, 95% CI 0.43-0.61), with a greater benefit in the first year
      (RR 0.46, 95% CI 0.38-0.55) when compared with subsequent years (RR 0.75, 95% CI
      0.59-0.94; P for interaction = 0.007). CONCLUSION: An early benefit of early
      generation DES in primary PCI for STEMI with a reduction in TVR and a trend
      towards less definite ST is offset in subsequent years by an increased risk of
      very late ST.

PMID- 22362514
TI  - Innate immune inflammatory response to danger: when, how, and why does a friend
      become a foe?

PMID- 22362516
TI  - Atypical secondary hypertension due to mid-aortic syndrome.

PMID- 22362515
TI  - SERCA2a gene therapy restores microRNA-1 expression in heart failure via an
      Akt/FoxO3A-dependent pathway.
AB  - AIMS: Impaired myocardial sarcoplasmic reticulum calcium ATPase 2a (SERCA2a)
      activity is a hallmark of failing hearts, and SERCA2a gene therapy improves
      cardiac function in animals and patients with heart failure (HF). Deregulation of
      microRNAs has been demonstrated in HF pathophysiology. We studied the effects of
      therapeutic AAV9.SERCA2a gene therapy on cardiac miRNome expression and focused
      on regulation, expression, and function of miR-1 in reverse remodelled failing
      hearts. METHODS AND RESULTS: We studied a chronic post-myocardial infarction HF
      model treated with AAV9.SERCA2a gene therapy. Heart failure resulted in a strong
      deregulation of the cardiac miRNome. miR-1 expression was decreased in failing
      hearts, but normalized in reverse remodelled hearts after AAV9.SERCA2a gene
      delivery. Increased Akt activation in cultured cardiomyocytes led to
      phosphorylation of FoxO3A and subsequent exclusion from the nucleus, resulting in
      miR-1 gene silencing. In vitro SERCA2a expression also rescued miR-1 in failing
      cardiomyocytes, whereas SERCA2a inhibition reduced miR-1 levels. In vivo, Akt and
      FoxO3A were highly phosphorylated in failing hearts, but reversed to normal by
      AAV9.SERCA2a, leading to cardiac miR-1 restoration. Likewise, enhanced sodium
      calcium exchanger 1 (NCX1) expression during HF was normalized by SERCA2a gene
      therapy. Validation experiments identified NCX1 as a novel functional miR-1
      target. CONCLUSION: SERCA2a gene therapy of failing hearts restores miR-1
      expression by an Akt/FoxO3A-dependent pathway, which is associated with
      normalized NCX1 expression and improved cardiac function.

PMID- 22362517
TI  - Influences of tobacco and alcohol use on hepatocellular carcinoma survival.
AB  - Prognosis of hepatocellular carcinoma (HCC) is generally poor. The role of
      modifiable lifestyle factors on HCC survival has been less studied. To examine
      whether prediagnosis smoking and alcohol affected HCC survival stratified by
      viral etiology, we conducted a prospective cohort study of 2,273 (1990 with viral
      hepatitis and 283 without) incident HCC cases aged 20-75 years who were enrolled
      between 1997 and 2004 from a Taiwanese multicenter study, and followed up through
      2007. Information on habitual smoking and alcohol consumption was obtained at
      baseline through personal interview. After follow-up to a maximum of 10 years,
      1,757 participants died and 1,488 (84.7%) were attributed to HCC. Prediagnosis
      smoking and alcohol worsened prognosis independent of each other and clinical
      predictors. The effects of both risky behaviors were limited to viral hepatitis
      related HCC and more profound among those with early-stage HCC. Risk for HCC
      specific mortality increased with increasing pack-years smoked and ethanol intake
      (all p < 0.001 for trend), with an additive effect shown for the two habits
      [hazard ratio (HR) for alcohol >= 46.2 g/day and >= 10 pack-years = 1.72, 95%
      confidence interval (CI) = 1.45-2.05]. For either habit, cessation reduced HCC
      specific mortality, but a significant mortality benefit occurred 10 years after
      abstinence (quitting smoking >= 10 years vs. continuing smokers: HR = 0.77, 95%
      CI = 0.61-0.97; quitting drinking >= 10 years vs. continuing drinkers: HR = 0.74,
      95% CI = 0.56-0.98). In conclusion, among patients with viral hepatitis-related
      HCC, prediagnosis smoking and alcohol have a deleterious effect on HCC survival.
      Quitting smoking or drinking alcohol could reduce the excess risk, but only after
      a long interval of cessation.

PMID- 22362518
TI  - The association between study characteristics and outcome in the relation between
      job stress and cardiovascular disease - a multilevel meta-regression analysis.
AB  - OBJECTIVES: Studies about job strain and cardiovascular disease (CVD) have
      yielded inconsistent results, which hinders making a firm conclusion about the
      association. Inconsistent findings may be the result of methodological
      differences. If the relative CVD risk is influenced by methodological
      differences, these differences should be explored in more detail in future
      research to clarify which methodological characteristics are inherent to obtain
      the most accurate estimate between job strain and CVD risk. By assessing how
      study characteristics are associated with the outcome, we take the first step in
      unraveling this association. In this review, we explore the following research
      question: are study characteristics associated with the size of the reported
      relative CVD risk? METHODS: A systematic literature search yielded 71 studies
      about job stress, assessed with the demand-control model, and CVD. Traditional
      meta-regression was extended enabling the use of correlated data to quantify
      heterogeneity within and between studies. RESULTS: Compared to studies that use
      the original Job Content Questionnaire (JCQ), studies in which a more deviant
      form of the JCQ was used yielded, on average, 43% higher estimates. Studies
      conducted in the USA yielded about 26% lower estimates compared to studies
      conducted in Scandinavian countries. CONCLUSIONS: Several study characteristics
      are associated with the size of the reported relative CVD risk. Many of these
      study features are related to the validity of the exposure and outcome assessment
      and are inherent to obtain an accurate estimate between work stress and CVD risk.
      More research is needed to clarify why these study features impact the average
      relative CVD risk.

PMID- 22362519
TI  - Butanol production from cane molasses by Clostridium saccharobutylicum DSM 13864:
      batch and semicontinuous fermentation.
AB  - Clostridium acetobutylicum strains used in most Chinese ABE (acetone-butanol
      ethanol) plants favorably ferment starchy materials like corn, cassava, etc.,
      rather than sugar materials. This is one major problem of ABE industry in China
      and significantly limits the exploitation of cheap waste sugar materials. In this
      work, cane molasses were utilized as substrate in ABE production by Clostridium
      saccharobutylicum DSM 13864. Under optimum conditions, total solvent of 19.80 g/L
      (13.40 g/L butanol) was reached after 72 h of fermentation in an Erlenmeyer
      flask. In a 5-L bioreactor, total solvent of 17.88 g/L was attained after 36 h of
      fermentation, and the productivity and yield were 0.50 g/L/h and 0.33 g ABE/g
      sugar consumption, respectively. To further enhance the productivity, a two-stage
      semicontinuous fermentation process was steadily operated for over 8 days (205 h,
      26 cycles) with average productivity (stage II) of 1.05 g/L/h and cell
      concentration (stage I) of 7.43 OD(660), respectively. The average batch
      fermentation time (stage I and II) was reduced to 21-25 h with average solvent of
      15.27 g/L. This study provides valuable process data for the development of
      industrial ABE fermentation process using cane molasses as substrate.

PMID- 22362520
TI  - Quality of life and physical activity among adults: population-based study in
      Brazilian adults.
AB  - OBJECTIVE: To analyze the association between leisure-time physical activity (PA)
      (walking, moderate- and vigorous-intensity activities) and transport (active
      commuting) with quality of life (QoL) domains (physical, social relations,
      environmental and psychological). METHODS: Participants were 1,461 adults (18-65
      years) living in the city of Curitiba, Brazil. QoL was assessed using the
      abbreviated WHOQoL questionnaire and PA through the IPAQ long version. Multiple
      linear regression models were used to analyze the relationship between PA types
      (walking, moderate and vigorous) and domains (leisure and transport) with QoL
      domains. RESULTS: Walking for leisure was positively associated with social
      relations (beta = 1.5; P = 0.011) and environment (beta = 3.3; P = 0.015) domains
      among men and with physical (beta = 3.2; P = 0.04), environment (beta = 4.1; P =
      0.011) and psychological (beta = 3.2; P = 0.009) domains among women. Moderate
      intensity PA was associated with all but the physical QoL domain among women.
      Among men, this association was observed only between insufficient levels of PA
      and the physical domain of QoL (beta = 3.0; P = 0.016). Vigorous PA was
      associated with social relations (beta = 3.4; P = 0.034) and psychological (beta
      = 4.2; P = 0.009) QoL domains. Transport PA was only associated with the physical
      QoL domain in men (beta = 3.1; P = 0.042). CONCLUSION: There is a positive
      relationship between PA and QoL, though this association varies according to the
      type and intensity of PA and differs across QoL domains. Unlike transport PA,
      leisure-time PA shows consistent association with QoL.

PMID- 22362521
TI  - The Cardiff Acne Disability Index (CADI): linguistic and cultural validation in
      Serbian.
AB  - PURPOSE: The aims of this study were to translate the Cardiff Acne Disability
      Index (CADI) into Serbian and to assess its validity and reliability in Serbian
      acne patients. METHODS: The CADI was translated and linguistically validated into
      Serbian according to published guidelines. This version of CADI, along with the
      Serbian version of Children's Dermatology Life Quality Index (CDLQI) and a short
      demographic questionnaire, was administrated to a cohort of secondary school
      pupils. The Global Acne Grading Score was used to measure the clinical severity
      of acne. The internal consistency reliability of the Serbian version of CADI was
      assessed by Cronbach's alpha coefficient while its concurrent validity was
      assessed by Spearman's correlation coefficient. Construct validity was examined
      by factor analysis. RESULTS: A total of 465 pupils completed questionnaires. Self
      reported acne was present in 76% of pupils (353/465). The Serbian version of CADI
      showed high internal consistency reliability (Cronbach's alpha coefficient =
      0.79). The mean item-total correlation coefficient was 0.74 with a range of 0.53
      0.81. The concurrent validity of the scale was supported by a moderate but highly
      significant correlation with the CDLQI (Spearman's rho = 0.66; P < 0.001). Factor
      analysis revealed the presence of two dimensions underlying the factor structure
      of the scale. CONCLUSIONS: The Serbian version of the CADI is a reliable, valid,
      and valuable tool for assessing the impact of acne on the quality of life of
      Serbian-speaking patients.

PMID- 22362522
TI  - Resin-tooth interfacial morphology and sealing ability of one-step self-etch
      adhesives: microleakage and SEM study.
AB  - OBJECTIVES: To compare microleakage of three self-etch adhesives and to analyze
      enamel surface morphology and interfacial morphology of resin-enamel and resin
      dentin interface under scanning electron microscope (SEM). EXPERIMENTAL DESIGN:
      Study was conducted in 65 extracted human premolars. Class V cavities were
      prepared in 45 teeth and assigned to three groups (n = 15) according to three
      self-etch adhesives (OptiBond All-in-One, iBond, and Adper Prompt L-Pop). After
      restoration, 10 samples from each group were used to assess microleakage at
      enamel and dentin margin. Five samples from each group were used for analysis of
      interfacial morphology at resin-enamel and resin-dentin interface under SEM.
      Remaining 20 teeth were used to prepare flat enamel buccal surfaces to analyze
      the difference in surface morphology after treatment with three adhesives (n = 5
      each) and 36% phosphoric acid treatment (n = 5). PRINCIPAL OBSERVATIONS: At
      enamel margin, Prompt L-Pop depicted least leakage of all the three adhesives and
      also showed best interfacial adaptation under SEM. At dentin margin, OptiBond All
      in-One showed significant less leakage than iBond and Prompt L-Pop. On flat
      enamel surface, phosphoric acid produced the most retentive etching pattern when
      compared with the three adhesives. CONCLUSION: Prompt L-Pop showed the best
      bonding effectiveness in enamel, whereas OptiBond All-in-One performed
      significantly better in dentin.

PMID- 22362523
TI  - The {V4Nb6O30} cluster: a new type of vanadoniobate anion structure.
AB  - A novel {V(4)Nb(6)O(30)} addenda: Through the successful introduction of a
      vanadium atom into the polyoxoniobate system, three novel compounds containing
      the same unprecedented mixed addenda vanadoniobate cluster {V(4)Nb(6)O(30)} were
      obtained. The incorporation of suitable atoms like V is an intriguing subject
      providing vast possibilities to enrich polyoxoniobate chemistry.

PMID- 22362524
TI  - Comparison of antemortem antimicrobial treatment regimens to antimicrobial
      susceptibility patterns of postmortem lung isolates from feedlot cattle with
      bronchopneumonia.
AB  - A retrospective study was performed to compare the treatment regimens in feedlot
      cattle that died with bovine respiratory disease (BRD) to the antimicrobial
      susceptibility patterns of the microorganisms isolated from lungs. Forty-three
      cattle submitted by the Willard Sparks Beef Research Center (WSBRC) to the
      Oklahoma Animal Disease Diagnostic Laboratory for postmortem examination during
      2007 had bronchopneumonia (acute = 16, subacute = 5, or chronic = 22). Lungs from
      cattle were cultured aerobically (40 cattle) and for Mycoplasma spp. (34 cattle).
      Susceptibility panels were performed. At least 1 BRD pathogen (Mannheimia
      haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis, or
      Arcanobacterium pyogenes) was isolated from 39 cattle, and 77% (30/39) had
      multiple organisms recovered. Mycoplasmal infections were common (25/34) and a
      major component of mixed infections (24/25). The majority (60%) of the M.
      haemolytica, P. multocida, and H. somni isolates were resistant to tetracycline.
      Most of the H. somni isolates (67%) were susceptible to tilmicosin (Ti),
      enrofloxacin (En), ceftiofur (Ce), and florfenicol, despite extensive treatment
      with Ti, En, and Ce (75% of isolates were from cattle that received each
      antimicrobial once). Most of the M. haemolytica (65%) and P. multocida (79%)
      isolates were susceptible to En and Ce, despite antemortem treatment of cattle
      with these antimicrobials. Hence, the current study reports a discrepancy between
      the antemortem treatment of clinical BRD and the susceptibility patterns of the
      bacteria isolated from lungs postmortem. Based on these findings, factors other
      than antimicrobial resistance are playing a role in the death of feedlot cattle
      with BRD.

PMID- 22362525
TI  - Measurement of beta-hydroxybutyrate in cats with nonketotic diabetes mellitus,
      diabetic ketosis, and diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes
      mellitus (DM). The standard method of detection of ketone bodies is the dipstick
      method, which detects semiquantitatively acetoacetate, but not beta
      hydroxybutyrate (beta-HB). The objectives of the current study were to assess the
      diagnostic utility of beta-HB to diagnose diabetic ketosis (DK) and DKA in cats
      and to establish a cut-off value for the diagnosis of DKA. Sixty-two cats were
      included in the study. Eleven cats were healthy (group 1); in the remainder of
      cats (51), a diagnosis of DM was based on hyperglycemia, glucosuria, and
      increased fructosamine concentrations. Nineteen of 51 cats suffered from
      nonketotic diabetes mellitus (group 2). In 11 cats, plasma ketone bodies were
      detected with the dipstick method (diabetic ketosis, group 3). In 21 cats, plasma
      ketone bodies and metabolic acidosis were present (DKA, group 4). Plasma beta-HB
      was measured in all cats by an enzymatic method (spectrophotometry). A cut-off
      value for the diagnosis of DKA was calculated based on the receiver operating
      characteristic curve. In healthy cats, the beta-HB concentration ranged from 0 to
      0.1 mmol/l; in cats of group 2, from 0 to 0.9 mmol/l (median: 0.1 mmol/l); in
      cats of group 3, from 0.6 to 6.8 mmol/l (median: 1.7 mmol/l); and in cats of
      group 4, from 3.8 to 12.2 mmol/l (median: 7.9 mmol/l). A cut-off value of 2.4
      mmol/l revealed 100% sensitivity and 87% specificity to diagnose DKA. Beta
      hydroxybutyrate is a useful parameter for the diagnosis of diabetic ketosis and
      DKA in cats.

PMID- 22362527
TI  - Evaluation of Flinders Technology Associates cards for collection and transport
      of samples for detection of Porcine reproductive and respiratory syndrome virus
      by reverse transcription polymerase chain reaction.
AB  - Blood, tissue and oral fluid samples collected from experimentally infected
      animals and field cases were used to evaluate the safety, diagnostic sensitivity
      and specificity of Flinders Technology Associates (FTA) cards for Porcine
      reproductive and respiratory syndrome virus (PRRSV) reverse transcription
      polymerase chain reaction (RT-PCR) diagnostics. The analytical sensitivity of
      PRRSV RT-PCR from serum and oral fluids in FTA cards was reduced, although the
      virus could still be detected at concentrations of 10(1) and 10(3) TCID/ml,
      respectively. The sensitivity and specificity of PRRSV RT-PCR detection from
      serum, blood, and tissue samples in cards collected from experimentally infected
      animals were 100%. Sensitivity for oral fluids was 45% (95% CI: 19.97-73.01)
      compared to fresh. For field samples, sensitivity was 89% (95% CI: 77.35-95.63)
      and 100% (95% CI: 80.00-100) for serum and lung samples, respectively. The
      sensitivity was the same for samples stored in cards at room temperature or at
      4oC, and tested overnight or after 14 days. Cards inoculated with PRRSV-positive
      samples did not yield replicating virus after cell culture. In conclusion, FTA
      cards proved to be a safe, simple, and sensitive alternative method to transport
      serum, blood, and tissue samples for PRRSV RT-PCR diagnostics; however, a
      significant decrease in RT-PCR sensitivity should be expected from oral fluid
      samples.

PMID- 22362526
TI  - Naturally occurring Influenza A virus subtype H1N2 infection in a Midwest United
      States mink (Mustela vison) ranch.
AB  - Influenza A virus (FLUAV) causes acute respiratory disease in humans and a
      variety of animal species. The virus tends to remain within the species of
      origin; nonetheless, naturally occurring cross-species transmission of FLUAV has
      been periodically documented. Multiple cross-species transmissions of FLUAV have
      been reported from companion animals and captive wild animals, neither of which
      is historically considered as natural hosts of FLUAV. In the fall of 2010, mink
      (Mustela vison) inhabiting a 15,000-head mink farm in the Midwest United States
      experienced persistent severe respiratory distress and nose and/or mouth
      bleeding. Mink losses averaged approximately 10 animals per day. Six dead mink at
      6 months of age were submitted to the Iowa State University Veterinary Diagnostic
      Laboratory for diagnostic investigation. Gross and microscopic examinations
      revealed that all 6 mink had hemorrhagic bronchointerstitial pneumonia. Hemolytic
      Escherichia coli was isolated from lungs, probably accounting for hemorrhagic
      pneumonia. All animals tested negative for Canine distemper virus and Aleutian
      mink disease virus. Interestingly, FLUAV of H1N2 subtype, which contained the
      matrix gene of swine lineage, was detected in the lungs. Serological follow-up on
      mink that remained in the ranch until pelting also confirmed that the ranch had
      been exposed to FLUAV of H1 subtype (delta clade). The case study suggests that
      FLUAV should be included in the differential diagnosis when mink experience
      epidemics of respiratory disease. Since the source of FLUAV appeared to be
      uncooked turkey meat, feeding animals fully cooked ration should be considered as
      a preventive measure.

PMID- 22362528
TI  - Synovial hemangioma in an adult horse.
AB  - A 15-year-old gelding presented with a progressive lameness of the left forelimb
      of 2.5 months duration. Clinically, a dilation of the deep flexor tendon sheath
      with a firm elastic consistency and a pronounced tenderness was noted.
      Ultrasonically, a marked swelling of the flexor tendon sheath with an irregular
      density of the mesotendineum was observed. The white, firm material forming a
      nodular distension of the flexor tendon sheath with a diameter of approximately 1
      cm was excised and sent for histopathological examination. Biopsies of the deep
      flexor tendon and corresponding tendon sheath were sent for histopathological
      evaluation. Histologically, the mass consisted of clefts and numerous
      anastomosing vascular channels extending between the collagen fibers of the deep
      flexor tendon. These capillary-like spaces were lined by neoplastic cells that
      were flattened to polygonal and contained few erythrocytes. There was 0 to 1
      mitotic figure per 10 high power fields (400*). Immunohistochemically, the
      neoplastic cells stained positive for vimentin and factor VIII-related antigen.
      Adjacent to the neoplastic endothelial cells located pericytes expressed alpha
      smooth muscle actin antigen. Based on the histopathological and
      immunohistochemical features, synovial hemangioma was diagnosed. One year after
      surgery, the horse has shown no lameness.

PMID- 22362529
TI  - Association between canine pancreatic-specific lipase and histologic exocrine
      pancreatic inflammation in dogs: assessing specificity.
AB  - The current study aimed to determine the specificity, and to a lesser extent the
      sensitivity, of canine pancreatic-specific lipase (cPL) concentration in dogs
      with various disease conditions. Dogs were presented for postmortem examination
      and had serum collected for cPL concentration within 6 hr preceding death or
      immediately postmortem. Pancreatic tissue was collected postmortem, and sections
      from the left lobe, right lobe, and body of the pancreas were examined
      histologically. Inflammation and fibrosis in each section were assessed to
      determine a total pancreatic inflammatory score and pancreatic fibrosis score in
      each dog. Correlations between these scores and the cPL concentration were made,
      as well as determination of specificity. A total of 32 dogs were included in the
      analysis, 20 of whom had no to minimal pancreatic inflammation. The specificity
      of cPL with a cutoff value of 200 ug/l was 80% (95% confidence interval [CI]: 56
      94%), while with a cutoff of 400 ug/l, the specificity was 90% (95% CI: 68-99%).
      There was a significant but rather low correlation between cPL concentration and
      the pancreatic inflammation score, but not with the fibrosis score. Canine
      pancreatic-specific lipase concentration has good specificity overall in dogs
      without pancreatitis. This test is less useful in dogs with milder pancreatitis,
      and both false-positive and false-negative results occur. Results indicated that
      dogs with clinical signs suggestive of pancreatitis would require abdominal
      imaging in addition to serum cPL testing to evaluate the cause (or causes) of
      clinical signs.

PMID- 22362530
TI  - Salmonella serovar distribution in cobras (Naja kaouthia), snake-food species,
      and farm workers at Queen Saovabha Snake Park, Thailand.
AB  - The purpose of the current study was to investigate the prevalence and serovar
      distribution of Salmonella isolates in cobras and their environment at a snake
      park. A total of 166 fecal or intestinal samples were examined, comprising 39
      samples from captive cobras (Naja kaouthia), 70 from recently wild-caught cobras,
      19 from wild-caught cobras that had been kept on the farm for over 3 months, 18
      from mice (Mus musculus), 12 from frogs (Hoplobatrachus rugulosus), and 8 from
      farm workers. Specific serological identification was performed, and pulsed-field
      gel electrophoresis (PFGE) was utilized for DNA analysis. Out of all snakes (n =
      128), 20 of the 30 animals used for snake food and 3 of the 8 samples from
      personnel were positive for Salmonella spp. There were 228 Salmonella isolates,
      with a total of 29 serovars from subspecies I and IIIb, composed of 24 serovars
      from cobras and 5 from the other sources. Salmonella Amsterdam was predominant in
      captive-born and captive cobras, followed by S. Poona and S. Bareilly,
      respectively (P < 0.05). Salmonella I 4,[5],12:i:- was the sole serovar detected
      from the mice, while 3 serovars including Ramatgan, I 4,[5],12:e,h:-, and rough
      strain were detected only from frogs (P < 0.001). Salmonella Derby was only
      detected in workers. On the basis of the PFGE results, evidence of movement of
      isolates between human beings and snakes, and between snakes and frogs, was found
      for S. Poona and S. Wandsworth, respectively. The study suggests that Salmonella
      spp. act as true residents in the intestinal tract of cobras with high risk of
      environmental contamination through fecal shedding.

PMID- 22362531
TI  - Bovine papular stomatitis affecting dairy cows and milkers in midwestern Brazil.
AB  - Bovine papular stomatitis virus (BPSV) is a parapoxvirus associated with papular
      and erosive lesions on the muzzle, lips, and oral mucosa of cattle. Teats of
      milking cows are occasionally affected, and the infection is frequently
      transmitted to human beings. The present report describes an outbreak of BPSV
      infection affecting cows in midwestern Brazil, with human involvement. The
      disease was observed in neighboring small hand-milking farms, affecting 20
      milking cows. The signs included painful reddish papules, ulcers, and scabby
      proliferative lesions on the teats, with a clinical course of 7-12 days. Affected
      cows presented severe local pain, not allowing the completion of milking.
      Histologically, acanthosis, spongiosis, and parakeratotic hyperkeratosis with
      adjacent focally extensive ulcers and multifocal inflammatory infiltrate were
      observed in the epidermis. Eosinophilic inclusion bodies were noted in the
      cytoplasm of epithelial cells. Personnel milking the affected cows developed
      lesions on the hands, painful papules that progressed to ulcerative and scabby
      lesions in 4-7 days. A polymerase chain reaction using a set of pan-parapoxvirus
      primers for the B2L gene performed on DNA extracted from scabs amplified a 590-bp
      product, which when sequenced, revealed similarities of 99%, 85%, and 84% with
      BPSV, Pseudocowpox virus, and Orf virus, respectively. A phylogenetic tree based
      on the B2L sequence was constructed, showing that the virus clustered with BPSV
      isolates. Although clinical cases compatible with BSPV infection have been
      frequently described in Brazil, the present report identifies the agent
      associated with cattle and human disease in the country.

PMID- 22362532
TI  - Comparison of Q fever serology methods in cattle, goats, and sheep.
AB  - Coxiella burnetii is an obligate intracellular bacterium that is responsible for
      the zoonotic disease Q fever. The distribution of this agent is worldwide except
      for New Zealand, and infection can be asymptomatic in both human beings and
      animals. Chronic exposures can produce abortions, stillbirths, and infertility
      issues in animals and endocarditis in human beings. A commercial enzyme-linked
      immunosorbent assay (ELISA) kit marketed in the European Union was purchased to
      compare C. burnetii antibody detection methods. The current study examined the
      agreement of ELISA and complement fixation results in over 668 diagnostic
      ruminant sera submitted to the National Veterinary Services Laboratories for Q
      fever serologic testing. The majority of combined sera (548) were negative on
      both tests. Fifty-seven of the combined sera were positive on both tests. There
      were 45 combined sera with low complement fixation titers at 1:10 and negative
      ELISA results. The results were surprising given the expectations that ELISA
      methods, by nature, amplify detection of antibody-antigen interactions leading to
      higher sensitivity. Potential mechanisms for these discrepant results are
      discussed.

PMID- 22362533
TI  - Urinary clusterin as a renal marker in dogs.
AB  - A validation of a species-specific enzyme immunoassay for urinary clusterin
      measurement in dogs was performed, and the use of urinary clusterin as a marker
      of renal damage was evaluated in a population of dogs with leishmaniasis. Urine
      was obtained from 75 dogs; 64 dogs had leishmaniasis and 11 were healthy. The
      dogs with leishmanias were divided into 5 groups: I (n = 9; serum creatinine
      [SCr] < 1.4 mg/dl, urinary protein-to-creatinine [UPC] ratio <= 0.5); II (n = 29;
      SCr < 1.4 mg/dl, UPC > 0.5); III (n = 6; SCr >= 1.4 mg/dl to <2 mg/dl, UPC >
      0.5); IV (n = 13; SCr >= 2 mg/dl to <5 mg/dl, UPC > 0.5); and V (n = 7; SCr >= 5
      mg/dl, UPC > 0.5). The urinary clusterin concentration was measured, and the
      urinary clusterin-to-creatinine ratio was calculated. Canine urinary clusterin
      assay showed good analytical performance based on precision accuracy and limit-of
      detection results. There was a statistically significant increase in urinary
      clusterin and clusterin-to-creatinine ratio in groups II-V compared with group I
      and healthy group. The results of the current study showed that urinary clusterin
      concentration and urinary clusterin-to-creatinine ratios are increased in dogs
      with analytical evidences of renal damage and that the urinary clusterin-to
      creatinine ratio might be used as a potential early biomarker of chronic kidney
      disease.

PMID- 22362534
TI  - A malignant and metastasizing feline cardiac ganglioneuroma.
AB  - In the current study, a case of a cardiac ganglioneuroma with systemic metastases
      in a cat is described. A 12-year-old male neutered Japanese domestic cat was
      brought to a veterinary hospital for dysorexia, coughing, vomiting, and diarrhea.
      Ultrasonography revealed a mass adjacent to the right atrium. The animal died of
      respiratory failure 1 month after the first visit to the hospital. At necropsy,
      an oval-shaped white mass 1.5 cm in diameter was observed within the right
      auricle. Diffusely, the right ventricle was infiltrated and thickened by the
      neoplastic lesion. Histologically, the mass was composed of 3 types of neoplastic
      cells: spindle cells, large polygonal cells, and small undifferentiated cells.
      Immunohistochemically, the neoplasia was positive for neuronal markers such as
      betaIII tubulin, S-100a, and protein gene product 9.5. Ultrastructurally, the
      large polygonal cells were characterized by abundant cytoplasm that included
      compressed Golgi cisternae and rough endoplasmic reticula and abundant
      intermediate filaments. A discontinuous basement membrane surrounded the spindle
      cells. Metastatic foci were found in the lungs, kidney, pancreas, urinary
      bladder, and adrenal glands. The morphological, immunohistochemical, and
      ultrastructural characteristics of the tumor cells were consistent with those of
      ganglioneuroma. The tumor was presumed to originate from the intramural
      parasympathetic ganglia in the right atrium.

PMID- 22362535
TI  - Usability of a gamma interferon release assay in the diagnosis of naturally
      infected pigs with Mycobacterium avium subspecies hominissuis.
AB  - In the current study, the results of an intradermal tuberculin test and a gamma
      interferon (IFN-gamma) release assay were compared. IFN-gamma release assay is
      based on the detection of IFN-gamma production after in vitro stimulation with
      Mycobacterium avium subsp. avium-specific antigen for the discrimination of pigs
      naturally infected with M. avium subsp. hominissuis. Fifty-five clinically
      healthy pigs were used in the study. Three of these were proven by culture and
      real-time quantitative polymerase chain reaction methods to be infected with M.
      avium subsp. hominissuis (2 animals) and Mycobacterium xenopi (1 animal). No
      animals were positive by the tuberculin test. Both M. avium subsp. hominissuis
      positive pigs were evaluated as positive by the IFN-gamma release assay.
      Bacteriologically negative and M. xenopi-positive pigs were unresponsive in the
      IFN-gamma release assay, indicating the specificity of the method. The results
      suggest that the IFN-gamma release assay has a higher sensitivity than the
      tuberculin test and that the assay can be used for diagnosis of M. avium
      infections in live, naturally infected pigs.

PMID- 22362536
TI  - Demonstration of Mycoplasma bovis by immunohistochemistry and in situ
      hybridization in an aborted bovine fetus and neonatal calf.
AB  - Mycoplasmas are host-specific commensals on mucous membranes of the genital
      tract, but infection and clinical disease by Mycoplasma bovis in the genital
      tract of cattle is not well described. In the current study, 1 aborted bovine
      fetus and 1 neonatal calf were examined macroscopically and histologically. For
      the detection of M. bovis, bacterial isolation, immunohistochemistry (IHC), and
      in situ hybridization (ISH) were performed. For further characterization of the
      inflammatory infiltrates, IHC was performed using antibodies to cluster of
      differentiation (CD)3, CD79a, lysozyme, L1, S-100A8, S-100A9, and von Willebrand
      factor VIII. Gross examination revealed a lobular consolidation of the lung.
      Histologically, the lungs of both animals showed an interstitial pneumonia
      associated with suppurative bronchopneumonia, intraalveolar multinucleated giant
      cells, and lymphocytic aggregates. The expression of L1, S-100A8, and S-100A9 in
      multinucleated giant cells supports a histiocytic origin. Mycoplasma bovis
      antigen was detected by IHC in brain, lung, liver, and placenta of the fetus, and
      M. bovis DNA was detected by ISH in various organs of the fetus, including lung
      and placenta and within the lung of the calf.

PMID- 22362537
TI  - An outbreak of pseudocowpox in fattening calves in southern Brazil.
AB  - Pseudocowpox virus is a parapoxvirus frequently associated with papulovesicular
      and scabby lesions on the teats and udders of milking cows and is often
      transmitted to human beings. An unusual outbreak of skin disease in fattening
      calves in southern Brazil is described. Fourteen of 17 male cattle (82%), aged 6
      48 months, feeding on grass pastures were affected. Animals developed papules,
      vesicles, and scabby proliferative lesions on the muzzle in a clinical course of
      approximately 10-15 days. The scabby lesions often presented with exudation and
      bleeding. Histological examination of mucocutaneous tissue in detached scabs
      revealed acanthosis with thickening of the corneal layer and premature
      keratinization (parakeratotic hyperkeratosis). The dermis had multifocal
      lymphoplasmacytic infiltrates. Electron microscopic examination of scab specimens
      revealed typical parapoxvirus particles: oval shaped (260 nm * 160 nm),
      enveloped, and covered with a helical layer. Polymerase chain reaction using a
      set of pan-parapoxvirus primers for the B2L gene amplified a 590-bp product out
      of DNA extracted from scabs. Nucleotide sequencing of the amplicons revealed a
      nucleotide homology of 97% with Pseudocowpox virus and lower homology with other
      parapoxviruses: Bovine papular stomatitis virus (84%) and Orf virus (94%). A
      phylogenetic tree based on the B2L sequence was constructed, showing that the
      virus clustered with Pseudocowpox virus isolates.

PMID- 22362538
TI  - Multiple endocardial neurofibromas in a rosy-billed pochard (Netta peposaca).
AB  - Endocardial neoplasms are uncommon in veterinary species with most cases
      restricted to endocardial schwannomas in aged rats. A 15-year-old male rosy
      billed pochard (Netta peposaca) was diagnosed following necropsy with numerous,
      proliferative endocardial masses. Histologically, these masses were composed of
      interlacing streams and bundles of neoplastic spindle cells supported by a fine
      fibrovascular stroma. Rare areas of cellular and nuclear palisading were present
      in the nodules. Approximately 60% of the neoplastic cells were strongly positive
      for S-100, whereas none of the neoplastic cells was positive for desmin,
      synaptophysin, neurofilament, and glial fibrillary acidic protein. The histologic
      features coupled with the S-100 immunoreactivity led to a diagnosis of
      endocardial neurofibroma.

PMID- 22362539
TI  - Alopecia areata in two black Angus cows.
AB  - Adult onset progressive alopecia and leukotrichia developed in 2 registered black
      Angus cows, aged 6 and 7 years. Histopathologic findings in skin were prominent
      melanin clumping and degeneration of matrix cells with formation of giant
      multinucleate cells within hair bulbs, accompanied by peribulbar melanin
      incontinence and fibrosis and dystrophic hair shafts. Intrabulbar and peribulbar
      lymphocytes were cluster of differentiation (CD)3-positive T cells. Findings were
      characteristic of alopecia areata.

PMID- 22362540
TI  - Antipsychotic prescribing in nursing homes.

PMID- 22362543
TI  - Microsatellite markers for the native Texas perennial grass, Panicum hallii
      (Poaceae).
AB  - PREMISE OF THE STUDY: We developed microsatellites for Panicum hallii for studies
      of gene flow, population structure, breeding experiments, and genetic mapping.
      METHODS AND RESULTS: Next-generation (454) genomic sequence data were used to
      design markers. Eighteen robust markers were discovered, 15 of which were
      polymorphic across six accessions of P. hallii var. hallii. Fourteen of the
      markers cross-amplified in a P. capillare accession. For the 15 polymorphic
      markers, the total number of alleles per locus ranged from two to 26 (mean: 11.0)
      across six populations (11-19 individuals per population). Observed
      heterozygosity (mean: 0.031) was 13.7 times lower than the expected
      heterozygosity (mean: 0.426). CONCLUSIONS: The deficit of heterozygous
      individuals is consistent with P. hallii having a high rate of self
      fertilization. These markers will be useful for studies in P. hallii and related
      species.

PMID- 22362544
TI  - High-throughput capture of nucleotide sequence polymorphisms in three Brassica
      species (Brassicaceae) using DNA microarrays.
AB  - PREMISE OF THE STUDY: To capture molecular markers that are applicable to
      environmental risk assessment of genetically modified oilseed rape, and to
      streamline their development, we screened variations in nucleotide sequences of
      three Brassica species by DNA microarray analysis. METHODS AND RESULTS: Using the
      Affymetrix GeneChip Arabidopsis ATH1 Genome Array, we monitored gene expression
      at 22810 loci among the Brassica species and picked out 192 putative polymorphic
      loci. We sequenced 25 of these and successfully aligned them among all three
      species. All 25 loci possessed some interspecific and at times intraspecific
      nucleotide variation. CONCLUSIONS: DNA microarray analysis effectively detected a
      large number of nucleotide sequence variations among closely related Brassica
      species. The polymorphic regions will allow the subsequent development of
      functional gene markers.

PMID- 22362541
TI  - Differential risk of death in older residents in nursing homes prescribed
      specific antipsychotic drugs: population based cohort study.
AB  - OBJECTIVE: To assess risks of mortality associated with use of individual
      antipsychotic drugs in elderly residents in nursing homes. DESIGN: Population
      based cohort study with linked data from Medicaid, Medicare, the Minimum Data
      Set, the National Death Index, and a national assessment of nursing home quality.
      SETTING: Nursing homes in the United States. PARTICIPANTS: 75,445 new users of
      antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine,
      risperidone, ziprasidone). All participants were aged >= 65, were eligible for
      Medicaid, and lived in a nursing home in 2001-5. MAIN OUTCOME MEASURES: Cox
      proportional hazards models were used to compare 180 day risks of all cause and
      cause specific mortality by individual drug, with propensity score adjustment to
      control for potential confounders. RESULTS: Compared with risperidone, users of
      haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence
      interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to
      0.88). The effects were strongest shortly after the start of treatment, remained
      after adjustment for dose, and were seen for all causes of death examined. No
      clinically meaningful differences were observed for the other drugs. There was no
      evidence that the effect measure modification in those with dementia or
      behavioural disturbances. There was a dose-response relation for all drugs except
      quetiapine. CONCLUSIONS: Though these findings cannot prove causality, and we
      cannot rule out the possibility of residual confounding, they provide more
      evidence of the risk of using these drugs in older patients, reinforcing the
      concept that they should not be used in the absence of clear need. The data
      suggest that the risk of mortality with these drugs is generally increased with
      higher doses and seems to be highest for haloperidol and least for quetiapine.

PMID- 22362545
TI  - Assessing allometric models to predict vegetative growth of mango (Mangifera
      indica; Anacardiaceae) at the current-year branch scale.
AB  - PREMISE OF THE STUDY: Accurate and reliable predictive models are necessary to
      estimate nondestructively key variables for plant growth studies such as leaf
      area and leaf, stem, and total biomass. Predictive models are lacking at the
      current-year branch scale despite the importance of this scale in plant science.
      METHODS: We calibrated allometric models to estimate leaf area and stem and
      branch (leaves + stem) mass of current-year branches, i.e., branches several
      months old studied at the end of the vegetative growth season, of four mango
      cultivars on the basis of their basal cross-sectional area. The effects of year,
      site, and cultivar were tested. Models were validated with independent data and
      prediction accuracy was evaluated with the appropriate statistics. KEY RESULTS:
      Models revealed a positive allometry between dependent and independent variables,
      whose y-intercept but not the slope, was affected by the cultivar. The effects of
      year and site were negligible. For each branch characteristic, cultivar-specific
      models were more accurate than common models built with pooled data from the four
      cultivars. Prediction quality was satisfactory but with data dispersion around
      the models, particularly for large values. CONCLUSIONS: Leaf area and stem and
      branch mass of mango current-year branches could be satisfactorily estimated on
      the basis of branch basal cross-sectional area with cultivar-specific allometric
      models. The results suggested that, in addition to the heteroscedastic behavior
      of the variables studied, model accuracy was probably related to the functional
      plasticity of branches in relation to the light environment and/or to the number
      of growth units composing the branches.

PMID- 22362546
TI  - Gene expression-targeted isoflavone therapy.
AB  - Lysosomal storage diseases (LSD) form a group of inherited metabolic disorders
      caused by dysfunction of one of the lysosomal proteins, resulting in the
      accumulation of certain compounds. Although these disorders are among first
      genetic diseases for which specific treatments were proposed, there are still
      serious unsolved problems that require development of novel therapeutic
      procedures. An example is neuronopathy, which develops in most of LSD and cannot
      be treated efficiently by currently approved therapies. Recently, a new potential
      therapy, called gene expression-targeted isoflavone therapy (GET IT), has been
      proposed for a group of LSD named mucopolysaccharidoses (MPS), in which storage
      of incompletely degraded glycosaminoglycans (GAGs) results in severe symptoms of
      virtually all tissues and organs, including central nervous system. The idea of
      this therapy is to inhibit synthesis of GAGs by modulating expression of genes
      coding for enzymes involved in synthesis of these compounds. Such a modulation is
      possible by using isoflavones, particularly genistein, which interfere with a
      signal transduction process necessary for stimulation of expression of certain
      genes. Results of in vitro experiments and studies on animal models indicated a
      high efficiency of GET IT, including correction of behavior of affected mice.
      However, clinical trials, performed with soy isoflavone extracts, revealed only
      limited efficacy. This caused a controversy about GET IT as a potential,
      effective treatment of patients suffering from MPS, especially neuronopathic
      forms of these diseases. It this critical review, I present possible molecular
      mechanisms of therapeutic action of isoflavones (particularly genistein) and
      suggest that efficacy of GET IT might be sufficiently high when using relatively
      high doses of synthetic genistein (which was employed in experiments on cell
      cultures and mouse models) rather than low doses of soy isoflavone extracts
      (which were used in clinical trials). This proposal can be tested in double
      blinded, placebo-controlled clinical trials.

PMID- 22362547
TI  - Long-term functional outcomes and patient perspective following altered
      fractionation radiotherapy with concomitant boost for oropharyngeal cancer.
AB  - With no long-term data available in published research to date, this study
      presents details of the swallowing outcomes as well as barriers to and
      facilitators of oral intake and weight maintenance at 2 years after altered
      fractionation radiotherapy with concomitant boost (AFRT-CB). Twelve patients with
      T1-T3 oropharyngeal cancer who received AFRT-CB were assessed at baseline, 6
      months, and 2 years post-treatment for levels of dysphagia and salivary toxicity,
      food and fluid tolerance, functional swallowing outcomes, patient-reported
      function, and weight. At 2 years, participants were also interviewed to explore
      barriers and facilitators of oral intake. Outcomes were significantly worse at 2
      years when compared to baseline for late toxicity, functional swallowing, and
      patient-rated physical aspects of swallowing. Most patients (83%) tolerated a
      full diet pretreatment, but the rate fell to 42% (remainder tolerated soft diets)
      at 2 years. Multiple barriers to oral intake that impacted on activity and
      participation levels were identified. Participants lost 11 kg from baseline to 2
      years, which was not regained between 6 months and 2 years. Global, social, and
      emotional domains of patient-reported function returned to pretreatment levels.
      At 2 years post AFRT-CB, worsening salivary and dysphagia toxicity, declining
      functional swallowing, and multiple reported ongoing barriers to oral intake had
      a negative impact on participants' activity and participation levels relating to
      eating. These ongoing deficits contributed to significant deterioration in
      physical swallowing functioning determined by the MDADI. In contrast, patients
      perceived their broader functioning had improved at 2 years, suggesting long-term
      adjustment to ongoing swallowing deficits.

PMID- 22362548
TI  - A qualitative assessment of human cadavers embalmed by Thiel's method used in
      laparoscopic training for renal resection.
AB  - Human cadaveric tissue is the fundamental substrate for basic anatomic and
      surgical skills training. A qualitative assessment of the use of human cadavers
      preserved by Thiel's method for a British Association of Urological Surgeons
      approved, advanced laparoscopic renal resection skills training course is
      described in the present study. Four trainees and four experienced laparoscopic
      surgeons participated in the course. All participants completed a five-point
      Likert scale satisfaction questionnaire after their training sessions. The
      quality of cadaveric tissue and the training session were assessed with
      particular emphasis placed on the ease of patient positioning, the ease of trocar
      placement, the preservation of tissue planes, the ease of renal pedicle
      dissection, and the quality of tissue preservation. All of the participants
      highly rated the quality of the cadaveric tissue embalmed by Thiel's method (mean
      scores for quality on the five-point Likert scale were 4.5 and 4.3 by the
      trainees and experienced laparoscopic surgeons, respectively). All of the steps
      of laparoscopic renal resection were rated 4.0 or more on the Likert scale by
      both trainees and faculty members. The initial response rates for using a human
      cadaver embalmed by Thiel's method as a training tool for laparoscopic
      nephrectomy showed encouraging results. The performance of a laparoscopic
      nephrectomy on a human cadaver embalmed by Thiel's method bears close resemblance
      to real laparoscopic nephrectomy procedures, and thus demonstrates added
      advantages to the previously reported models.

PMID- 22362550
TI  - Limitations of Cockcroft-Gault and MDRD formulas in estimating GFR among top
      level rugby players.
AB  - INTRODUCTION: We measured serum creatinine concentrations in 17 male athletes of
      the Italian national rugby team. METHODS: Blood was obtained before the start of
      training and during the competitive season. Serum creatinine level was measured
      by Jaffe reaction at 4 time points during the season, with a formal measure of
      creatinine clearance in midseason. RESULTS: The values of estimated glomerular
      filtration rate (eGFR) calculated with the Cockcroft-Gault (CG) equation were
      higher than those calculated with the Modification of Diet in Renal Disease
      (MDRD) Study formula (p<0.001). This difference was significantly decreased but
      still present when the MDRD formula was corrected for body surface area (BSA).
      When compared with measured creatinine clearance (CrCl), the MDRD underestimates
      the CrCl by 51 ml/min (95% confidence interval [95% CI], 36-67 ml/min, p<0.0001).
      When corrected for BSA, this difference falls to 27 ml/min (95% CI, 13-44 ml/min,
      p=0.001). The CG eGFR gave a better estimate of CrCl, differing by 1 ml/min (95%
      CI, -16 to +17 ml/min, p=NS). CONCLUSIONS: The MDRD formula underestimates the
      CrCl in rugby players, even when corrected for BSA. Conversely, the CG formula
      more closely approximates the actual CrCl measurement. The equations to estimate
      GFR should be used with caution in subjects having atypical anthropometric
      characteristics.

PMID- 22362551
TI  - New therapeutic approaches for resistant hypertension.
AB  - In the past few years, 2 new procedures have been developed for the treatment of
      resistant hypertension: electrical stimulation of carotid baroreceptors and
      catheter-based renal denervation. Both of these procedures have a solid
      pathophysiological background, which is based on the evidence that carotid
      baroreceptors and renal nerves are involved in the pathogenesis of different
      forms of experimental hypertension, potentiating sympathetic cardiovascular
      influence and thus promoting the development and progression of elevated blood
      pressure values. This paper will review the results of the clinical trials
      performed so far making use of each of the 2 above-mentioned approaches. The pros
      and cons of each intervention as well as the questions that remain to be
      addressed in the future will also be discussed.

PMID- 22362552
TI  - Effects of micronutrients on DNA repair.
AB  - BACKGROUND: DNA repair is an essential cellular function, which, by removing DNA
      damage before it can cause mutations, contributes crucially to the prevention of
      cancer. Interest in the influence of micronutrients on DNA repair activity is
      prompted by the possibility that the protective effects of fruits and vegetables
      might thus be explained. Two approaches to measuring repair-monitoring cellular
      removal of DNA damage and incubating cell extract with specifically damaged DNA
      in an in vitro assay-have been applied in cell culture, whole animal studies, and
      human trials. In addition, there are numerous investigations at the level of
      expression of DNA repair-related genes. RESULTS: Depending on the pathway studied
      and the phytochemical or food tested, there are varied reports of stimulation,
      inhibition or no effect on DNA repair. The clearest findings are from human
      supplementation trials in which lymphocytes are assessed for their repair
      capacity ex vivo. Studying cellular repair of strand breaks is complicated by the
      fact that lymphocytes appear to repair them very slowly. Applying the in vitro
      repair assay to human lymphocytes has revealed stimulatory effects on repair of
      oxidised bases by various micronutrients or a fruit- and vegetable-rich diet,
      while other studies have failed to demonstrate effects. CONCLUSIONS: Despite
      varied results from different studies, it seems clear that micronutrients can
      influence DNA repair, usually but not always enhancing activity. Different modes
      of DNA repair are likely to be subject to different regulatory mechanisms.
      Measures of gene expression tend to be a poor guide to repair activity, and there
      is no substitute for phenotypic assays.

PMID- 22362553
TI  - Orofacial manifestations in HIV positive children attending Mildmay Clinic in
      Uganda.
AB  - The aim of this study was to assess the orofacial manifestations and their
      influence on oral function in human immunodeficiency virus (HIV) positive
      children attending Mildmay Clinic in Uganda. This was a cross-sectional study
      based on clinical examination, medical records and a structured questionnaire of
      368 children aged between 1.5 and 17 years. The clinical examination for dental
      caries was based on decayed, extracted and filled teeth (deft) and decayed,
      missing and filled teeth (DMFT) indices as defined by World Health Organisation.
      The soft tissue orofacial lesions were assessed using the classification and
      diagnostic criteria as described by the Collaborative Workgroup on the Oral
      Manifestations of Pediatric HIV Infections. Approximately 67.4% of the children
      were on highly active antiretroviral therapy (HAART). The majority (77.4%) of the
      children had at least one orofacial lesion associated with HIV, pseudomembranous
      candidiasis being the most prevalent. Overall, 61.7% of the children with
      orofacial lesions reported at least one form of discomfort in the mouth.
      Discomfort was particularly associated with swallowing. The prevalence of
      orofacial lesions was significantly higher in children with poor oral hygiene and
      lower in those on HAART than in their respective counterparts. The CD4+ cell
      count, age and gender of the children did not significantly influence the
      distribution of orofacial lesions. The mean deft and DMFT scores were 11.8 and
      2.7, respectively. The d- and D-components contributed 54.7 and 42.1%,
      respectively. Consumption of sugary snacks was directly associated with dental
      caries. Despite these children attending an HIV care centre of excellence, they
      have a high prevalence of orofacial manifestations associated with HIV. The
      majority of the children experienced discomfort in the oral cavity, particularly
      during swallowing.

PMID- 22362555
TI  - Wet atmospheric deposition of nitrogen: 20 years measurement in Shenzhen City,
      China.
AB  - We presented measurements of wet deposition of NH(4)(+)-N and NO(3)(-)-N from
      1986 to 2006 in Shenzhen City, China. Over the past 20 years, NO(3)(-)-N
      concentration had significantly increased, but a reverse trend was found for
      NH(4)(+)-N. The main form of total inorganic nitrogen (TIN) was NH(4)(+)-N and
      the average NH(4)(+)-N/NO(3)(-)-N ratio was 1.57 in this area. The contribution
      of NO(3)(-)-N to TIN increased from 28-42% in the period of 1986-2000 to 50-63%
      during 2001-2006. The increased deposition flux of NO(3)(-)-N resulted in the
      increasing trend of TIN, although NH(4)(+)-N showed a decreasing trend over time.
      Average deposition flux of TIN during 1986-2006 was 13.24 kg/ha/year, with a
      minimum value of 6.03kg/ha/year in 1988 and a maximum value of 20.52 kg/ha/year
      in 1997. Wet deposition fluxes of N appeared to vary with season, 81% occurred in
      the warm season (from April to September). The wet deposition of TIN to the
      Shenzhen Reservoir reached 8,902 kg in 2006, which contributed 9.95% of the total
      nonpoint pollution to the reservoir and will be increased in the future.

PMID- 22362554
TI  - Histone deacetylase inhibitors enhance the apoptotic activity of insulin-like
      growth factor binding protein-3 by blocking PKC-induced IGFBP-3 degradation.
AB  - Overexpression of insulin-like growth factor binding protein (IGFBP)-3 induces
      apoptosis of cancer cells. However, preexisting resistance to IGFBP-3 could limit
      its antitumor activities. This study characterizes the efficacy and mechanism of
      the combination of recombinant IGFBP-3 (rIGFBP-3) and HDAC inhibitors to overcome
      IGFBP-3 resistance in a subset of non-small cell lung cancer (NSCLC) and head and
      neck squamous cell carcinoma (HNSCC) cells. The effects of the combination of
      rIGFBP-3 and a number of HDAC inhibitors on cell proliferation and apoptosis were
      assessed in vitro and in vivo by using the MTT assay, a flow cytometry-based
      TUNEL assay, Western blot analyses and the NSCLC xenograft tumor model. Combined
      treatment with HDAC inhibitors and rIGFBP-3 had synergistic antiproliferative
      effects accompanied by increased apoptosis rates in a subset of NSCLC and HNSCC
      cell lines in vitro. Moreover, combined treatment with depsipeptide and rIGFBP-3
      completely suppressed tumor growth and increased the apoptosis rate in vivo in
      H1299 NSCLC xenografts. Evidence suggests that HDAC inhibitors increased the half
      life of rIGFBP-3 protein by blocking protein kinase C (PKC)-mediated
      phosphorylation and degradation of rIGFBP-3. In addition, combined treatment of
      IGFBP-3 with an HDAC inhibitor facilitates apoptosis through upregulation of
      rIGFBP-3 stability and Akt signaling inhibition. The ability of HDAC inhibitors
      to decrease PKC activation may enhance apoptotic activities of rIGFBP-3 in NSCLC
      cells in vitro and in vivo. These results indicated that combined treatment with
      HDAC inhibitor and rIGFBP-3 could be an effective treatment strategy for NSCLC
      and HNSCC with highly activated PKC.

PMID- 22362556
TI  - Monitoring variation in greenhouse gases concentration in urban environment of
      Delhi.
AB  - Cities across the globe are considered as major anthropogenic sources of
      greenhouse gases (GHG), yet very few efforts has been made to monitor ambient
      concentration of GHG in cities, especially in a developing country like India.
      Here, variations in the ambient concentrations of carbon dioxide (CO(2)) and
      methane (CH(4)) in residential, commercial, and industrial areas of Delhi are
      determined from fortnightly daytime observations from July, 2008 to March, 2009.
      Results indicate that the average daytime ambient concentration of CO(2) varied
      from 495 to 554 ppm in authorized residential areas, 503 to 621 ppm in the slums
      or jhuggies in the unauthorized residential areas, 489 to 582 ppm in commercial
      areas, and 512 to 568 ppm in industrial areas with an average of 541 +/- 27 ppm.
      CH(4) concentration varied from 652 to 5,356 ppbv in authorized residential
      areas, 500 to 15,220 ppbv in the unauthorized residential areas, 921 to 11,000
      ppbv in the commercial areas, and 250 to 2,550 ppbv in the industrial areas with
      an average of 3,226 +/- 1,090 ppbv. A low mid-afternoon CO(2) concentration was
      observed at most of the sites, primarily due to strong biospheric photosynthesis
      coupled with strong vertical mixing.

PMID- 22362557
TI  - Analysis of spatial and seasonal distributions of MODIS aerosol optical
      properties and ground-based measurements of mass concentrations in the Yellow Sea
      region in 2009.
AB  - Satellite-retrieved data on aerosol optical depth (AOD) and Angstrom exponent
      (AE) using a moderate resolution imaging spectrometer (MODIS) were used to
      analyze large-scale distributions of atmospheric aerosols in East Asia. AOD was
      relatively high in March (0.44 +/- 0.25) and low in September (0.24 +/- 0.21) in
      the East Asian region in 2009. Sandstorms originating from the deserts and dry
      areas in northern China and Mongolia were transported on a massive scale during
      the springtime, thus contributing to the high AOD in East Asia. However, whereas
      PM10 with diameters <=10 MUm was the highest in February at Anmyon, Cheongwon,
      and Ulleung, located leeward about halfway through the Korean Peninsula, AOD rose
      to its highest in May. The growth of hygroscopic aerosols attendant on increases
      in relative humidity prior to the Asian monsoon season contributed to a high AOD
      level in May. AE typically appears at high levels (1.30 +/- 0.37) in August due
      to anthropogenic aerosols originating from the industrial areas in eastern China,
      while AOD stays low in summer due to the removal process caused by rainfall. The
      linear correlation coefficients of the MODIS AOD and ground-based mass
      concentrations of PM10 at Anmyon, Cheongwon, and Ulleung were measured at
      0.4~0.6. Four cases (6 days) of mineral dustfall from sandstorms and six cases
      (12 days) of anthropogenically polluted particles were observed in the central
      area of the Korean Peninsula in 2009. PM10 mass concentrations increased at both
      Anmyon and Cheongwon in the cases of mineral dustfall and anthropogenically
      polluted particles. Cases of dustfall from sandstorms and anthropogenic polluted
      particles, with increasing PM10 mass concentrations, showed higher AOD values in
      the Yellow Sea region.

PMID- 22362558
TI  - Persistent high on-treatment platelet reactivity in acute coronary syndrome.
AB  - Persistent high on-treatment platelet reactivity in acute coronary syndrome (ACS)
      patients managed with appropriate antiplatelet therapy has been correlated with
      increased risk of cardiovascular events; however, the evolution of this
      phenomenon overtime is not well known. We investigated platelet activity at a
      three month follow-up after initial presentation with an ACS. We enrolled a total
      of 124 patients in the study, 65 were diagnosed with ACS and 59 controls who
      presented with non-cardiac chest pain for baseline comparisons. Of the enrolled
      patients, we had 25 ACS patients return, in stable condition, three months after
      their initial presentation for repeat platelet functional testing. Epinephrine
      (EPI), adenosine diphosphate (ADP), and arachidonic acid induced platelet
      aggregation were monitored at baseline with repeat measurement of EPI- and ADP
      stimulated aggregation at follow-up. In addition, P-selectin and PAC-1 expression
      were monitored at presentation and at a three month follow-up period. ACS
      patients were maintained on aspirin therapy during the intervening period. At the
      three month follow-up visit, ACS patients initiated on aspirin had no significant
      percentage change in aggregation to submaximal concentrations of EPI and ADP.
      They also had no significant percentage change in PAC-1 or P-selectin expression.
      This study demonstrates persistent high on-treatment platelet reactivity in ACS
      patients at a three month follow-up, which may place these patients at increased
      risk of recurrent cardiovascular events.

PMID- 22362559
TI  - Anticoagulation after subcutaneous enoxaparin is time sensitive in STEMI patients
      treated with tenecteplase.
AB  - The adequacy of anticoagulation with enoxaparin as an adjuvant to fibrinolytic
      therapy for STEMI is unclear and has implications for both efficacy and safety;
      especially in patients undergoing a pharmacoinvasive reperfusion strategy. A
      subset of fibrinolytic-treated patients in the WEST study was enrolled in a
      systematic anti-Xa substudy. All received ASA and subcutaneous (SQ) enoxaparin 1
      mg/kg followed by TNK-tPA. Incremental IV dosing of enoxaparin (0.3-0.5 mg/kg)
      was allowed prior to percutaneous coronary intervention (PCI). Anti-Xa blood
      samples were drawn prior and after angiography. Data are presented as
      percentages, medians and IQRs. Forty-five patients underwent angiography 2.8 h
      (2.5-14.6) after fibrinolytic. The pre-angiography median anti-Xa acquired 179
      min (153-875) after SQ enoxaparin was 0.48 U/ml (0.42-0.65); a relationship
      between anti-Xa activity and time from administration was evident (r = 0.418, p <
      0.007). Without supplemental IV enoxaparin the 2nd anti-Xa acquired 218 min (195
      930) after SQ enoxaparin was 0.48 U/ml (0.41-0.80, n = 29). After supplemental IV
      enoxaparin, the 2nd anti-Xa was 0.92 U/ml (0.72-1.10, n = 16). An incremental IV
      enoxaparin dose and anti-Xa relationship was demonstrated (r = 0.59, p = 0.001)
      i.e. no IV 0.48 U/ml (0.41-0.80, n = 29), 0.3 mg/kg IV 0.81 U/ml (0.63-1.00, n =
      12), and 0.5 mg/kg IV 1.34 U/ml (1.16-1.54, n = 4). Most fibrinolytic treated
      STEMI patients receiving weight-adjusted SQ enoxaparin (1 mg/kg) had
      subtherapeutic anti-Xa levels (<0.5 U/ml) after ~3 h. A strategy of supplemental
      0.3 mg/kg IV enoxaparin at time of PCI reliably achieved anti-Xa >= 0.5 U/ml. Our
      findings provide a rational novel strategy for anti-thrombotic management in
      STEMI patients undergoing a pharmacoinvasive reperfusion strategy.

PMID- 22362560
TI  - Miniaturization of metal-biomolecule frameworks based on stereoselective self
      assembly and potential application in water treatment and as antibacterial
      agents.
AB  - Miniaturization of metal-biomolecule frameworks (MBioFs) to the nanometer scale
      represents a novel strategy for fabricating materials with tunable physical and
      chemical properties. Herein, we demonstrate a simple, low-cost, and completely
      organic solvent-free strategy for constructing a dl-glutamic acid-copper ion
      based three-dimensional nanofibrous network structure. The building blocks used
      are available in large quantities and do not require any laborious synthesis or
      modification. Importantly, we demonstrate with an intriguing example, that the
      self-assembly ability of supramolecular nanofibers could be finely tuned with the
      ligands' chirality. This offers opportunities for obtaining one-dimensional
      hierarchical nanostructures and expands the investigation scope of
      stereoselective self-assembly. Furthermore, the material displays good ability in
      removing anionic dyes from water and inhibits the growth of both Gram positive
      and Gram negative bacteria, possibly through the contact-killing mechanism; this
      indicates potential applications in environmental issues and antimicrobial
      nanotherapeutics.

PMID- 22362561
TI  - Bone marrow cells of swine: collection and separation.
AB  - Bone marrow is a source of stem cells for greater and easier access, which is
      widely studied as a provider of hematopoietic and mesenchymal cells for various
      purposes, mainly therapeutic by the advances in research involving cell therapy.
      The swine is an animal species commonly used in the pursuit of development of
      experimental models. Thus, this study aimed to standardize protocol for
      collection and separation of bone marrow in swines, since this species is widely
      used as experimental models for various diseases. Twelve animals were used, which
      underwent bone marrow puncture with access from the iliac crest and cell
      separation by density gradient followed by a viability test with an average of
      98% of viable cells. Given our results, we can ensure the swine as an excellent
      model for obtaining and isolation of mononuclear cells from bone marrow,
      stimulating several studies addressing the field of cell therapy.

PMID- 22362562
TI  - The SOCS box-adapting proteins for ubiquitination and proteasomal degradation.
AB  - The suppressor of cytokine signalling (SOCS) box was first identified in the SH2
      containing SOCS box family (cytokine-inducible SH2-containing protein, SOCS1-7)
      and is a 40-amino acid motif, which functions to recruit an E3 ubiquitin ligase
      complex consisting of the adapter proteins elongins B and C, Rbx2 and the
      scaffold protein Cullin5. The SOCS box is found in a diverse array of
      intracellular signalling molecules, many of which contain different protein
      interaction domains such as SPRY and WD40 domains, leucine and ankyrin repeats or
      other functional domains such as GTPases. In general, the SOCS box-containing
      proteins are thought to act as substrate-recognition modules to mediate the
      polyubiquitination and subsequent degradation of substrate proteins by the 26S
      proteasome.

PMID- 22362564
TI  - The role of AlF3 coatings in improving electrochemical cycling of Li-enriched
      nickel-manganese oxide electrodes for Li-ion batteries.
AB  - A Li[Li(0.19)Ni(0.16)Co(0.08)Mn(0.57)]O(2) cathode was coated with AlF(3) on the
      surface. The AlF(3)-coating enhanced the overall electrochemical characteristics
      of the electrode while overcoming the typical shortcomings of lithium-enriched
      cathodes. This improvement was attributed to the transformation of the initial
      electrode layer to a spinel phase, induced by the Li chemical leaching effect of
      the AlF(3) coating layer.

PMID- 22362565
TI  - Regenerable resistive switching in silicon oxide based nanojunctions.
AB  - A nanomemristor based on SiO(2)  is fabricated in situ with spatial control at
      the nanoscale. The proposed system exhibits peculiar properties such as the
      possibility to be regenerated after being stressed or damaged and the possibility
      to expose the metal and the oxide interfaces by removing the top electrodes.

PMID- 22362566
TI  - High gas pressure: an innovative method for the inactivation of dried bacterial
      spores.
AB  - In this article, an original non-thermal process to inactivate dehydrated
      bacterial spores is described. The use of gases such as nitrogen or argon as
      transmission media under high isostatic pressure led to an inactivation of over 2
      logs CFU/g of Bacillus subtilis spores at 430 MPa, room temperature, for a 1 min
      treatment. A major requirement for the effectiveness of the process resided in
      the highly dehydrated state of the spores. Only a water activity below 0.3 led to
      substantial inactivation. The solubility of the gas in the lipid components of
      the spore and its diffusion properties was essential to inactivation. The main
      phenomenon involved seems to be the sorption of the gas under pressure by the
      spores' structures such as residual pores and plasma membranes, followed by a
      sudden drop in pressure. Observation by phase-contrast microscopy suggests that
      internal structures have been affected by the treatment. Some parallels with
      polymer permeability to gas and rigidity at various water activities offer a few
      clues about the behavior of the outer layers of spores in response to this
      parameter and provide a good explanation for the sensitivity of spores to high
      gas pressure discharge at low hydration levels. Specificity of microorganisms
      such as size, organization, and composition could help in understanding the
      differences between spores and yeast regarding the parameters required for
      inactivation, such as pressure or maintenance time.

PMID- 22362568
TI  - An improved gas chromatography screening method for doping substances using
      triple quadrupole mass spectrometry, with an emphasis on quality assurance.
AB  - A GC-QqQ-MS method was developed for the detection of over 150 compounds from
      different classes (steroids, narcotics, stimulants, beta-blockers, beta-2
      agonists and hormone antagonists) in a qualitative way. In the quantitative part,
      the traditional steroid profile with the most important endogenous steroids is
      expanded with six minor metabolites, which further improves the detection and
      identification of endogenous steroid abuse. In addition to these,
      norandrosterone, salbutamol and the major metabolite of cannabis are also
      quantified. Methods developed for anti-doping purposes should be subjected to the
      highest level of quality. Here, the addition of a combination of (deuterated)
      internal standards allows for an accurate quality control of every single step of
      the methodology: hydrolysis efficiency, derivatization efficiency and
      microbiological degradation are monitored in every single sample. Additionally,
      special attention is paid to the relationships between parameters indicating
      degradation by micro-organisms and the reliability of the steroid profile. The
      impact of the degradation is studied by evaluation of the quantities and
      percentages of 5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione. The
      concept of measurement uncertainty was introduced for the evaluation of relative
      abundances of mass-to-charge ratios and the obtained ranges were compared with
      the World Anti-Doping Agency regulations on tolerance windows for relative ion
      intensities. The results indicate that the approaches are similar.

PMID- 22362569
TI  - Editorial: Special issue on the 7th Symposium of the EWDTS on Workplace Drug
      Testing.

PMID- 22362570
TI  - Regulatory aspects of workplace drug testing in Europe.
AB  - Workplace drug testing in Europe is governed by a patchwork of legislation--or
      lack of it. Other difficulties are caused by language, currency and a host of
      other factors, including the difficulty in defining 'safety critical'. The
      European Workplace Drug Testing Society's (EWDTS) history and objectives are
      briefly outlined. Some of the problems peculiar to testing in Europe are
      discussed. Finally, some of the legislation in the different countries is
      described.

PMID- 22362571
TI  - A snapshot of workplace drug testing in Italy.
AB  - The Italian Decree on Health and Safety at Work (81/08) prescribes mandatory drug
      tests for jobs which pose safety hazards to others. Workplace drug testing is
      performed in accordance with the Provision of the Government-Regions Conference,
      2008. The aim of our survey was to examine the prevalence of drug use and the
      main drug findings in a sample of Italian workers performing hazardous jobs. From
      September 2009 to February 2011, 551 urine samples were collected in 42 Italian
      companies. Sample collection was carried out at the workplace by qualified
      laboratory personnel sent from the Institute of Occupational Medicine of the
      Catholic University (UCSC) of Rome. The workers to be tested were informed the
      day before, as the law requires. The samples were checked for adulteration,
      coded, and sent immediately to the laboratory of the UCSC Forensic Toxicology
      Analytical Unit. The screening test was an immunoassay. The positive samples
      proceeded to the confirmatory analysis with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The urine samples were analyzed for cannabis, opiates,
      amphetamines, methamphetamines, cocaine, methadone, and MDMA. Out of 16 samples
      .9% screened positive; only 4 of them (0.7%) were confirmed with the LC-MS/MS.
      Confirmed results included cocaine (2 samples), cannabis (1 sample), both cocaine
      and cannabis (1 sample). The prevalence of positive samples was lower than
      expected. Such finding cannot be explained by a low reliability of the testing
      procedure but could be due to test scheduling. More positive cases might be found
      performing short-notice random testing.

PMID- 22362572
TI  - False-positive cannabis results in Italian workplace drug testing.

PMID- 22362573
TI  - Legal workplace policies for drugs and alcohol in Turkey.
AB  - The widespread of individual and social problems related to substance use/abuse
      provoked the new approaches for workplace drug testing systems in the world.
      Workplace drug testing laws are constructed to protect the community from the
      consequences of drug use by workers. In Turkey, the legal arrangements on
      workplace drug testing exist in Turkish Penal Code, Turkish Labour Law, Workplace
      Physicians Regulations, Maritime Labour Law and Medical Examination Instructions
      in Highway Transportation Although Turkey has made the initial attempts to
      develop homogeneous and reliable regulations for workplace drug testing, a
      detailed workplace policy for drug testing at workplace has still not been
      provided.. An amendment has been done in the Regulations on Seafarers and a drug
      test (marijuana, cocaine, amphetamine like drugs and opiate) has been added into
      the routine tests to take a "Seafarer Health Report".

PMID- 22362574
TI  - Workplace drug testing, different matrices different objectives.
AB  - Drug testing is used by employers to detect drug use by employees or job
      candidates. It can identify recent use of alcohol, prescription drugs, and
      illicit drugs as a screening tool for potential health and safety and performance
      issues. Urine is the most commonly used sample for illicit drugs. It detects the
      use of a drug within the last few days and as such is evidence of recent use; but
      a positive test does not necessarily mean that the individual was impaired at the
      time of the test. Abstention from use for three days will often produce a
      negative test result. Analysis of hair provides a much longer window of
      detection, typically 1 to 3 months. Hence the likelihood of a falsely negative
      test using hair is very much less than with a urine test. Conversely, a negative
      hair test is a substantially stronger indicator of a non-drug user than a
      negative urine test. Oral fluid (saliva) is also easy to collect. Drugs remain in
      oral fluid for a similar time as in blood. The method is a good way of detecting
      current use and is more likely to reflect current impairment. It offers promise
      as a test in post-accident, for cause, and on-duty situations. Studies have shown
      that within the same industrial settings, hair testing can detect twice as many
      drug users as urine testing.

PMID- 22362577
TI  - A smart gelator as a chemosensor: application to integrated logic gates in
      solution, gel, and film.
AB  - A gelator that consisted of one benzimidazole moiety and four amide units was
      used as a chemosensor. We found that its absorption and emission spectra in
      solution were sensitive to two complementary chemical stimuli: protons and
      anions. Thus, YES and INH logic gates were obtained when absorbance was defined
      as an output. A combination gate of XNOR and AND with an emission output was also
      obtained. Moreover, wet gels in two solvents were used to construct two more
      complicated three-input-three-output gates, owing to the existence of the gel
      phase as an additional output. Finally, in xerogel films that were formed from
      two kinds of wet gels, reversible changes in their emission spectra were observed
      when they were sequentially exposed to volatile acid and NH(3). Another
      combination two-output logic gate was obtained for xerogel films. Finally, three
      states of the gelator were used to construct not only basic logic gate, but also
      some combination gates because of their response to multiple chemical stimuli and
      their multiple output signals, in which one chemical input could erase the effect
      of another chemical input.

PMID- 22362576
TI  - Dietary- and tissue-based exposure of belted kingfisher to PCDFs and PCDDs in the
      Tittabawassee River floodplain, Midland, MI, USA.
AB  - Concentrations of polychlorinated dibenzofurans (PCDFs) and other dioxin-like
      compounds in soils and sediments of the Tittabawassee River and associated
      floodplains downstream of Midland, Michigan, USA, are greater than upstream
      sites. As a result of these concentrations, which are some of the greatest ever
      reported, a site-specific exposure assessment of belted kingfisher breeding in
      the assessment area was conducted. To reduce the uncertainty associated with
      predicting exposure from abiotic matrices, concentrations of residues were
      quantified in site-specific prey items and in eggs and nestlings of belted
      kingfisher. Dietary exposure, expressed as the potential average daily dose,
      based on site-specific concentrations of PCDFs, polychlorinated dibenzo-p-dioxins
      (PCDDs), and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ(WHO-Avian)) in
      prey items was consistently greater along the Tittabawassee River than in
      associated reference areas and further downstream sites in the Saginaw River.
      Concentrations of PCDD/DFs in eggs and nestlings of belted kingfisher varied
      among sampling areas, being greater in both eggs and nestlings nesting along the
      Tittabawassee River compared to those of belted kingfisher from upstream
      reference areas. Geometric mean concentrations of PCDD/DFs were 130 and 200 ng/kg
      wet weight in eggs and nestlings of belted kingfisher, respectively. These
      concentrations are the equivalent of 84 and 95 ng TEQ(WHO-Avian)/kg. Site
      specific biomagnification factors for select PCDD/DF congeners ranged from <1.0
      to 1.8 in belted kingfisher.

PMID- 22362575
TI  - Role of IL-17 in psoriasis and psoriatic arthritis.
AB  - The role of T cell subpopulations in human disease is in a transition phase due
      to continuous discovery of new subsets of T cell, one of which is Th17,
      characterized by the production of signature cytokine IL-17. In the last couple
      of years, many articles are coming out on the role of Th17 and its signature
      cytokine IL-17 in different autoimmune diseases like rheumatoid arthritis,
      psoriasis, psoriatic arthritis (PsA), SLE and multiple sclerosis. Psoriasis and
      PsA are immune-mediated diseases, affecting the skin and joints, respectively.
      Initially, it was thought that psoriasis and PsA were Th1-mediated diseases;
      however, studies in knockout animal models (IL-17 knockout mice) as well as human
      experimental data indicate that Th17 and its signature cytokine IL-17 have a
      critical role in the pathogenesis of psoriatic disease. Th17 cells have been
      identified from the dermal extracts of psoriatic lesions. Subsequently, our
      research group has substantiated this observation that Th17 cells are enriched in
      the papillary dermis of psoriatic plaques and in freshly isolated effector T
      lymphocytes from the synovial fluid of PsA patients, and we have reported that
      the majority of these CD4 + IL-17+ T cells are of memory phenotype
      (CD4RO(+)CD45RA(-)CD11a(+)). Recent reports also suggest that the synovial tissue
      in psoriatic arthritis is enriched with IL-17R, and its most well recognized
      receptor IL-17RA is functionally active in psoriatic arthritis. In this review
      article, we have discussed the role of IL-17 in psoriatic disease and have
      narrated about the novel IL17/IL-17R antibodies currently in preparation for its
      therapeutic uses in autoimmune diseases.

PMID- 22362578
TI  - Influence of atomic force microscopy acquisition parameters on thin film
      roughness analysis.
AB  - A reliable procedure for measuring parameters connected to surface roughness is
      needed to compare the gas sensing properties of various thin films or the effect
      of different fabrication procedures on the surface roughness and the sensing
      properties. In this article, we propose to investigate how the acquisition
      parameters specific to atomic force microscopy investigations such as pixel size,
      scan area and scan speed influence the roughness parameters, namely root mean
      square and surface area ratio, commonly used for characterizing the gas sensing
      properties of porphyrins and other materials.

PMID- 22362579
TI  - IAPS and ubiquitylation.
AB  - The Inhibitor of apoptosis (IAP) proteins are key negative regulators of cell
      death, whose amplification has been correlated with tumor progression. Due to the
      presence of a RING domain, IAP proteins are classed as ubiquitin ligases and
      regulate cell survival by orchestrating a variety of ubiquitin modifications.
      Ubiquitin protein modification is fundamental in cell signaling and different
      ubiquitin modifications may label proteins for destruction, relocalization or
      provide a recruitment platform for ubiquitin binding proteins. Ubiquitin performs
      a myriad of different functions because it can be conjugated to a large range of
      target proteins through numerous different types of ubiquitin linkages. Despite
      the fact that ubiquitin is extremely versatile, the E3s such as the IAPs provide
      an important level of control due to their specificity for certain substrates.
      Several recent reviews have discussed the role of IAPs in regulating immune
      signaling so we have therefore focused our review on the interplay between IAPs
      and ubiquitin and discussed the importance of this relationship for the
      regulation of themselves, specific substrates and various cell death and survival
      signaling pathways.

PMID- 22362580
TI  - Unraveling the mechanism of molecular doping in organic semiconductors.
AB  - The mechanism by which molecular dopants donate free charge carriers to the host
      organic semiconductor is investigated and is found to be quite different from the
      one in inorganic semiconductors. In organics, a strong correlation between the
      doping concentration and its charge donation efficiency is demonstrated.
      Moreover, there is a threshold doping level below which doping simply has no
      electrical effect.

PMID- 22362582
TI  - The influence of health and lifestyle characteristics on the relation of serum 25
      hydroxyvitamin D with risk of colorectal and breast cancer in postmenopausal
      women.
AB  - The authors' objective was to discern whether lifestyle or health-related factors
      were confounders, effect modifiers, or irrelevant with regard to understanding
      observational associations of serum 25-hydroxyvitamin D (25(OH)D) with colorectal
      and breast cancer. The authors conducted nested case-control studies of
      colorectal cancer (310 cases, 310 controls) and breast cancer (1,080 cases, 1,080
      controls) in the Women's Health Initiative Calcium and Vitamin D Clinical Trial
      (1994-2005). Case-control matching factors included age, latitude,
      race/ethnicity, and blood collection date. Serum 25(OH)D was assayed in baseline
      fasting blood. Conditional logistic regression was used to estimate odds ratios
      for each cancer by serum 25(OH)D concentration, comparing the relative effects of
      successively adding body mass index, physical activity, and other health and
      lifestyle characteristics particular to each cancer. In models with matching
      factors only, low (vs. high) serum 25(OH)D was associated with a colorectal
      cancer odds ratio of 2.72 (95% confidence interval (CI): 1.55, 4.77) and a breast
      cancer odds ratio of 1.33 (95% CI: 1.02, 1.72). In multivariate-adjusted models
      for colorectal cancer, the association strengthened (OR = 4.45, 95% CI: 1.96,
      10.10). However, in multivariate-adjusted breast cancer models, associations were
      no longer significant (OR = 1.06, 95% CI: 0.78, 1.43). Adjusting for health and
      lifestyle characteristics has differential effects depending on the cancer site;
      when modeling such relations, investigators should take these factors into
      account.

PMID- 22362583
TI  - Economic conditions and suicide rates in New York City.
AB  - Extant analyses of the relation between economic conditions and population health
      were often based on annualized data and were susceptible to confounding by
      nonlinear time trends. In the present study, the authors used generalized
      additive models with nonparametric smoothing splines to examine the association
      between economic conditions, including levels of economic activity in New York
      State and the degree of volatility in the New York Stock Exchange, and monthly
      rates of death by suicide in New York City. The rate of suicide declined linearly
      from 8.1 per 100,000 people in 1990 to 4.8 per 100,000 people in 1999 and then
      remained stable from 1999 to 2006. In a generalized additive model in which the
      authors accounted for long-term and seasonal time trends, there was a negative
      association between monthly levels of economic activity and rates of suicide; the
      predicted rate of suicide was 0.12 per 100,000 persons lower when economic
      activity was at its peak compared with when it was at its nadir. The relation
      between economic activity and suicide differed by race/ethnicity and sex. Stock
      market volatility was not associated with suicide rates. Further work is needed
      to elucidate pathways that link economic conditions and suicide.

PMID- 22362585
TI  - Purification of monoclonal antibodies, IgG1, from cell culture supernatant by use
      of metal chelate convective interaction media monolithic columns.
AB  - Monoclonal antibodies (MAbs) have diverse applications in diagnostics and
      therapeutics. The recent advancement in hybridoma technology for large-scale
      production of MAbs in bioreactors demands rapid and efficient purification
      methods. Conventional affinity purification systems have drawbacks of low flow
      rates and denaturation of antibodies owing to harsh elution conditions. Here, we
      attempted purification of MAbs by use of a high-throughput metal-chelate
      methacrylate monolithic system. Monolithic macroporous convective interaction
      media-iminodiacetate (CIM-IDA) disks immobilized with four different metal ions
      (Cu2+, Ni2+, Zn2+ and Co2+) were used and evaluated for purification of anti
      human serum albumin IgG1 mouse MAbs from cell culture supernatant after
      precipitation with 50% ammonium sulfate. Elution with 10 mM imidazole in the
      equilibration buffer (25 mM MMA = MOPS (Morpholino propane sulfonic acid) + MES
      (Morpholino ethane sulfonic acid) + Acetate + 0.5 M NaCl, pH 7.4) resulted in a
      purification of 25.7 +/- 2.9-fold and 32.5 +/- 2.6-fold in experiments done using
      Zn2+ and Co2+ metal ions, respectively. The highest recovery of 85.4 +/- 1.0% was
      obtained with a CIM-IDA-Zn(II) column. SDS-PAGE, ELISA and immuno-blot showed
      that the antibodies recovered were pure, with high antigen-binding efficiency.
      Thus, metal chelate CIM monoliths could be a potential alternative to
      conventional systems for fast and efficient purification of MAbs from the complex
      cell culture supernatant.

PMID- 22362586
TI  - Purity of antidotal oxime HI-6 DMS as an active pharmaceutical ingredient for
      auto-injectors and infusions.
AB  - As reactivators of inhibited acetylcholinesterase, oximes are essential antidotes
      in poisoning by organophosphorus compounds. Due to its superior efficacy in cases
      of soman, cyclosarin, and sarin poisoning, the oxime HI-6 represents a promising
      option for an active pharmaceutical ingredient (API) in the further development
      of antidote therapy for nerve agent poisoning. Developmental lots of HI-6 DMS
      (dimethanesulfonate) provided by different manufacturers were examined with
      respect to their content and purity with a view to their future use as an API.
      There are distinct differences in the HI-6 content from three manufacturers. With
      respect to purity, gradual differences arise with the known synthetic by-products
      as well as with unknown accompanying compounds. It became apparent that in the
      case of a modified synthesis using protective groups, the proportion of some
      synthesis by-products decreases considerably. With one exception, they are thus
      below the reporting threshold for API in accordance with pertinent regulatory
      guidelines. In HI-6, an unknown impurity always occurs, whose percentage
      necessitates identification due to regulations. This unknown impurity, which has
      not been described so far, could be identified as an isomer. These findings
      supply data required for the description of pharmaceutical quality in accordance
      with module 3 of a Common Technical Document (CTD). They thus contribute to the
      marketing authorization of this substance as an API for auto-injectors and
      infusions.

PMID- 22362588
TI  - A cationic phospholipid-detergent conjugate as a new efficient carrier for siRNA
      delivery.

PMID- 22362587
TI  - Differential expression of genes involved in the degeneration and regeneration
      pathways in mouse models for muscular dystrophies.
AB  - The genetically determined muscular dystrophies are caused by mutations in genes
      coding for muscle proteins. Differences in the phenotypes are mainly the age of
      onset and velocity of progression. Muscle weakness is the consequence of myofiber
      degeneration due to an imbalance between successive cycles of
      degeneration/regeneration. While muscle fibers are lost, a replacement of the
      degraded muscle fibers by adipose and connective tissues occurs. Major
      investigation points are to elicit the involved pathophysiological mechanisms to
      elucidate how each mutation can lead to a specific degenerative process and how
      the regeneration is stimulated in each case. To answer these questions, we used
      four mouse models with different mutations causing muscular dystrophies, Dmd
      (mdx), SJL/J, Large (myd) and Lama2 (dy2J) /J, and compared the histological
      changes of regeneration and fibrosis to the expression of genes involved in those
      processes. For regeneration, the MyoD, Myf5 and myogenin genes related to the
      proliferation and differentiation of satellite cells were studied, while for
      degeneration, the TGF-beta1 and Pro-collagen 1alpha2 genes, involved in the
      fibrotic cascade, were analyzed. The result suggests that TGF-beta1 gene is
      activated in the dystrophic process in all the stages of degeneration, while the
      activation of the expression of the pro-collagen gene possibly occurs in mildest
      stages of this process. We also observed that each pathophysiological mechanism
      acted differently in the activation of regeneration, with distinctions in the
      induction of proliferation of satellite cells, but with no alterations in
      stimulation to differentiation. Dysfunction of satellite cells can, therefore, be
      an important additional mechanism of pathogenesis in the dystrophic muscle.

PMID- 22362589
TI  - Ultrastructure of larvae and puparia of the blowfly Chrysomya megacephala
      (Diptera: Calliphoridae).
AB  - Chrysomya megacephala is a forensic important fly, and its immature forms also
      cause myiasis. The adults are the first insects to reach a carcass and can
      oviposit just a few hours after arrival. Therefore, the knowledge of immature
      stages of flies is essential for correct identification of the species found on
      corpses. Scanning electron microscopy (SEM) gives detailed information on the
      morphological characters that can help identify the immature forms of flies. The
      aim of this study is to identify larvae and puparia of C. megacephala using SEM.
      The larval instar body of C. megacephala is similar at all instars. The
      integument is smooth with small spines located at the limit of all segments. The
      cephalic region has a group of robust spines with one or two tips. The puparia
      are very similar to third instar larvae, except for the cephalic structures that
      are retracted. The integument shows the wrinkles from the third instar larvae and
      posterior spiracle disc with three spiracular openings localized on the top of an
      elevation. In conclusion, SEM provides some characteristics to distinguish among
      Chrysomya species that could help entomologists to identify immature found on
      corpses.

PMID- 22362584
TI  - A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen
      receptor-negative and -positive breast cancers.
AB  - BRCA1 encodes a tumour suppressor protein that plays pivotal roles in homologous
      recombination (HR) DNA repair, cell-cycle checkpoints, and transcriptional
      regulation. BRCA1 germline mutations confer a high risk of early-onset breast and
      ovarian cancer. In more than 80% of cases, tumours arising in BRCA1 germline
      mutation carriers are oestrogen receptor (ER)-negative; however, up to 15% are ER
      positive. It has been suggested that BRCA1 ER-positive breast cancers constitute
      sporadic cancers arising in the context of a BRCA1 germline mutation rather than
      being causally related to BRCA1 loss-of-function. Whole-genome massively parallel
      sequencing of ER-positive and ER-negative BRCA1 breast cancers, and their
      respective germline DNAs, was used to characterize the genetic landscape of BRCA1
      cancers at base-pair resolution. Only BRCA1 germline mutations, somatic loss of
      the wild-type allele, and TP53 somatic mutations were recurrently found in the
      index cases. BRCA1 breast cancers displayed a mutational signature consistent
      with that caused by lack of HR DNA repair in both ER-positive and ER-negative
      cases. Sequencing analysis of independent cohorts of hereditary BRCA1 and
      sporadic non-BRCA1 breast cancers for the presence of recurrent pathogenic
      mutations and/or homozygous deletions found in the index cases revealed that
      DAPK3, TMEM135, KIAA1797, PDE4D, and GATA4 are potential additional drivers of
      breast cancers. This study demonstrates that BRCA1 pathogenic germline mutations
      coupled with somatic loss of the wild-type allele are not sufficient for
      hereditary breast cancers to display an ER-negative phenotype, and has led to the
      identification of three potential novel breast cancer genes (ie DAPK3, TMEM135,
      and GATA4).

PMID- 22362590
TI  - Does a redox cycle provide a mechanism for setting the capacity of neuroglobin to
      protect cells from apoptosis?
AB  - We hypothesize that the various, previously reported, reactivities of neuroglobin
      with redox partners and oxygen provide for the establishment of a redox cycle
      within cells, such as neurons and retinal rod cells. Using native cell lysates,
      from cultured human cells of neuronal origin, we have estimated the rate of
      reduction of the oxidized form of neuroglobin in vivo. Furthermore we provide
      evidence that the cytosol of these cells contains factors (presumably enzymes)
      capable of employing either glutathione or NADH as re-reductants of ferric
      neuroglobin. Taken in conjunction with previous rate data, for the various redox
      reactions of neuroglobin, this information allows us to set up a computer model
      to estimate the steady state cellular level of the antiapoptotic ferrous form of
      neuroglobin. This model indicates that the steady state level of antiapoptotic
      neuroglobin is very sensitive to the cellular oxygen tension and moderately
      sensitive to the redox status of the cell. Further analysis indicates that such a
      system would be capable of significant modification, on the seconds time scale,
      following hypoxic transition, as is likely in stroke. We hypothesize that this
      mechanism might provide a moderately rapid mechanism for adjusting the
      antiapoptotic status of a cell, whilst the reaction of neuroglobin with
      mitochondrial cytochrome c provides a very rapid, but limited, capacity to
      intervene in the apoptotic pathway.

PMID- 22362591
TI  - Analytical characterization of three trifluoromethyl-substituted methcathinone
      isomers.
AB  - Cathinone derivatives display a wide range of pharmacological activities and
      uses; some of them are used as prescription medicines, while others are
      encountered within a recreational context and are available without a
      prescription over the Internet and in retail shops around the world. One of the
      difficulties involved in the unambiguous identification of these new psychoactive
      substances is the lack of suitable reference standards, particularly when dealing
      with unreported derivatives and positional isomers. In order to address this
      need, three trifluoromethyl analogues of the psychostimulant methcathinone, with
      a CF(3) substituent at the 2-, 3- and 4-position of the phenyl ring (2-TFMAP 1, 3
      TFMAP 2 and 4-TFMAP 3), have been prepared for analytical characterization using
      ATR-FTIR, (1)H and (13) C NMR, and GC-(EI/CI)-ion trap-MS. Differentiation among
      isomers was feasible by IR, for example when assessing the carbonyl stretch at
      1711 (1), 1693 (2) and 1688 (3) cm(-1) , respectively. In addition to the
      expected iminium base peak at m/z 58, EI-MS displayed key ions at m/z 173, 145,
      125, 95, and 75. Separation of isomers was possible under GC conditions. A
      characteristic feature under CI conditions was the loss of water from the [M +
      H](+) yielding m/z 214 in addition to m/z 58. Studies currently underway show
      that the three CF(3) -methcathinone analogues have central nervous system effects
      and that the 4-CF(3) isomer 3 is more potent as a serotonin uptake inhibitor and
      releasing agent than the 3-CF(3) and 2-CF(3) counterparts.

PMID- 22362592
TI  - Creation of nanostuctures by extreme conditions: high-pressure synthesis of
      ultrahard nanocrystalline cubic boron nitride.
AB  - The synthesis of high-purity bulk nanostructured cubic boron nitride (cBN) at 20
      GPa and 1770 K by direct phase transformation of graphite-like BN with an "ideal
      random layer" structure is reported. The two-times increase of hardness of nano
      cBN (H(V)  = 85 GPa) with respect to conventional polycrystalline cBN (H(V)  ~ 45
      GPa) is evidently a result of nanosize effects.

PMID- 22362594
TI  - Surgeons condemn Lansley for misinformation on outcomes of knee operations.

PMID- 22362593
TI  - Genome-wide RNA interference analysis of renal carcinoma survival regulators
      identifies MCT4 as a Warburg effect metabolic target.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype
      of kidney cancer. Here, we integrated an unbiased genome-wide RNA interference
      screen for ccRCC survival regulators with an analysis of recurrently
      overexpressed genes in ccRCC to identify new therapeutic targets in this disease.
      One of the most potent survival regulators, the monocarboxylate transporter MCT4
      (SLC16A3), impaired ccRCC viability in all eight ccRCC lines tested and was the
      seventh most overexpressed gene in a meta-analysis of five ccRCC expression
      datasets. MCT4 silencing impaired secretion of lactate generated through
      glycolysis and induced cell cycle arrest and apoptosis. Silencing MCT4 resulted
      in intracellular acidosis, and reduction in intracellular ATP production together
      with partial reversion of the Warburg effect in ccRCC cell lines. Intra-tumoural
      heterogeneity in the intensity of MCT4 protein expression was observed in primary
      ccRCCs. MCT4 protein expression analysis based on the highest intensity of
      expression in primary ccRCCs was associated with poorer relapse-free survival,
      whereas modal intensity correlated with Fuhrman nuclear grade. Consistent with
      the potential selection of subclones enriched for MCT4 expression during disease
      progression, MCT4 expression was greater at sites of metastatic disease. These
      data suggest that MCT4 may serve as a novel metabolic target to reverse the
      Warburg effect and limit disease progression in ccRCC.

PMID- 22362595
TI  - India reaches milestone of no cases of wild poliovirus for 12 months.

PMID- 22362596
TI  - Watchdog claims more accurate GP lists will save NHS 6.1m pounds sterling.

PMID- 22362597
TI  - Puberty reveals a familial disorder of sex development.

PMID- 22362598
TI  - First toxicity data of chlorophenols on marine alga Dunaliella tertiolecta:
      correlation of marine algal toxicity with hydrophobicity and interspecies
      toxicity relationships.
AB  - The toxicity of phenol and 13 chlorinated phenols to the marine alga Dunaliella
      tertiolecta is presented for the first time. The newly generated marine algal
      toxicity data was found to correlate strongly with the widely used hydrophobicity
      parameter-the logarithm of the n-octanol-water partition coefficient (log K(OW)).
      Interspecies relationships using the new marine algal toxicity data of
      chlorophenols with the previously published data on bacterium (Vibrio fischeri),
      protozoan (Tetrahymena pyriformis), daphnid (Daphnia magna), freshwater alga
      (Pseudokirchneriella subcapitata), and fish (Pimephales promelas) revealed
      promising results that could be exploited in extrapolations using freshwater data
      to predict marine algal toxicity.

PMID- 22362599
TI  - Interpersonal psychotherapy for eating disorders.
AB  - Interpersonal psychotherapy (IPT) is a leading evidence-based treatment for those
      eating disorders in which binge eating is a feature. This article begins with a
      consideration of the rationale for using IPT to treat patients with eating
      disorders. This is followed by a review of the evidence supporting its use and a
      brief description of treatment including an illustrative clinical case vignette.
      The article closes with a discussion of possible future directions for research
      on IPT for eating disorders.

PMID- 22362600
TI  - Potential mechanisms underlying the associations between liver enzymes and risk
      for type 2 diabetes.

PMID- 22362601
TI  - Cell cycle-related kinase links androgen receptor and beta-catenin signaling in
      hepatocellular carcinoma: why are men at a loss?

PMID- 22362602
TI  - Mice with artificial human liver.

PMID- 22362603
TI  - Dendron-containing tetraphenylethylene compounds: dependence of fluorescence and
      photocyclization reactivity on the dendron generation.
AB  - The synthesis and characterization of four dendron-containing
      tetraphenylethylenes (TPEs), 1(1)-1(4), were synthesized, along with a TPE
      compound that contained four OCH(2) Ph groups (referred to as 1(0)) for
      comparison. Photophysical studies revealed that the TPE core became emissive
      after linking dendrons onto its periphery. Moreover, the fluorescence intensity
      was significantly enhanced when high-generation dendrons were linked onto the TPE
      core; the fluorescence intensity increased in the following order:
      1(1)<1(2)<1(3)<1(4). This phenomenon was tentatively attributed to an enhancement
      in the energy barrier for internal rotation and torsion of the TPE core to which
      four dendrons were connected. In addition, the photocyclization of the TPE core
      into the respective 9,10-diphenylphenanthrene was facilitated when high
      generation dendrons were linked to the TPE core. Again, the photocycliztion
      reactivity increased in the following order: 1(1)<1(2)<1(3)<1(4). We found that
      the fluorescence and photocyclization reactivity of TPE could be modulated by
      covalent interactions with dendrons, and such modulation was strongly dependent
      on the dendron-generation.

PMID- 22362604
TI  - Spectrofluorimetric determination of oseltamivir phosphate through derivatization
      with o-phthalaldehyde. Application to pharmaceutical preparations with a
      preliminary study on spiked plasma samples.
AB  - A simple and sensitive spectrofluorimetric method has been developed and
      validated for the determination of oseltamivir phosphate (OST) in pharmaceutical
      preparations. The method is based on the reaction between oseltamivir phosphate
      and o-phthalaldehyde in presence of 2-mercapto-ethanol in borate buffer, pH 10.8,
      to give a highly fluorescent product measured at 450 nm after excitation at 336
      nm. The different experimental parameters affecting the development and stability
      of the reaction product were studied and optimized. The fluorescence intensity
      concentration plot is rectilinear over the range 0.05-1.0 ug/mL, with a lower
      detection limit of 5 ng/mL and limit of quantitation of 16 ng/mL. The developed
      method was successfully applied to the analysis of the drug in its commercial
      capsules and suspension, mean recoveries of OST were 99.97 +/- 1.67% and 100.17
      +/- 1.18%, respectively (n = 3). Statistical comparison of the results obtained
      by the proposed and comparison method revealed no significant difference in the
      performance of the two methods regarding accuracy and precision. The proposed
      method was further extended to in vitro determination of the studied drug in
      spiked human plasma as a preliminary investigation; the mean recovery (n = 3) was
      98.68 +/- 5.8%. A reaction pathway was postulated.

PMID- 22362605
TI  - Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis
      stimulating agents in current and preventive doping analysis.
AB  - Increasing the blood's capacity for oxygen transport by erythropoiesis
      stimulating agents (ESAs) constitutes a prohibited procedure of performance
      enhancement according to the World Anti-Doping Agency (WADA). The advent of
      orally bio-available small-molecule ESAs such as hypoxia-inducible factor (HIF)
      stabilizers in the development of novel anti-anaemia therapies expands the list
      of potential ESA doping techniques. Here, the erythropoiesis-stimulating
      properties and doping relevance of experimental HIF-stabilizers, such as
      cobaltous chloride, 3,4-dihydroxybenzoic acid or GSK360A, amongst others, are
      discussed. The stage of clinical trials is reviewed for the anti-anaemia drug
      candidates FG-2216, FG-4592, GSK1278863, AKB-6548, and BAY85-3934. Currently
      available methods and strategies for the determination of selected HIF
      stabilizers in sports drug testing are based on liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). For the support
      of further analytical assay development, patents claiming distinct compounds for
      the use in HIF-mediated therapies are evaluated and exemplary molecular
      structures of HIF stabilizers presented. Moreover, data concerning the
      erythropoiesis-enhancing effects of the GATA inhibitors K7174 and K11706 as well
      as the lipidic small-molecule ESA PBI-1402 are elucidated the context of doping
      analysis.

PMID- 22362606
TI  - A graphite-like zero gap semiconductor with an interlayer separation of 2.8 A.
AB  - The synthesis of a highly crystalline graphite-like new material with an
      interlayer separation of 2.8 A is demonstrated by re-stacking GO sheets in the
      form of a thin film. The optical absorption spectra and electrical data indicate
      that the new crystal phase is an indirect zero gap semiconductor.

PMID- 22362607
TI  - Music and lexical tone perception in Chinese adult cochlear implant users.
AB  - OBJECTIVES/HYPOTHESIS: The present study's aim was to assess the music perception
      ability for Chinese adult cochlear implant users and to investigate the
      correlation between music and Mandarin-Chinese lexical tone perception. STUDY
      DESIGN: Case-control study. METHODS: Twenty normal-hearing and 21 adult cochlear
      implant users participated in the Musical Sounds in Cochlear Implants (MuSIC)
      perception test, including six objective and two subjective musical subtests. The
      comparison of music perception performance was made between normal-hearing and
      cochlear implant subjects. Sixteen of the 21 cochlear implant users also
      performed a tone identification test to investigate the correlation between music
      and tone perception. RESULTS: Cochlear implant users performed significantly
      worse than normal-hearing subjects on pitch discrimination, instrument
      identification, and instrument detection tests, whereas close to normal-hearing
      subjects on melody discrimination, chords discrimination, rhythm discrimination,
      and emotion and dissonance rating subtests. Lexical tone perception was
      significantly correlated with pitch discrimination, melody discrimination, and
      instrument identification tests. Duration of hearing aid use was found to be
      correlated with pitch discrimination ability of cochlear implant users.
      CONCLUSIONS: Chinese postlingually deafened cochlear implant users performed
      significantly poorer in pitch discrimination and timbre perception tasks than
      normal-hearing listeners. Lexical tone perception was found to be significantly
      correlated with music pitch perception, supporting the notion that tone and music
      perception may share a similar pitch perception mechanism.

PMID- 22362608
TI  - Considering the frontomedian cortex in revised criteria for behavioural variant
      frontotemporal dementia.

PMID- 22362609
TI  - Evaluation of the performance of Trima Accel(r) v5.2 for the collection of
      concentrated high-dose platelet products and concurrent plasma from high platelet
      count donors, in Germany.
AB  - BACKGROUND AND OBJECTIVES: This study was undertaken to test the ability of Trima
      Accel(r) version 5.2 to simultaneously collect concentrated high-dose
      leukoreduced platelet products and double doses of plasma. MATERIALS AND METHODS:
      Random volunteers (18-65 years of age) with preprocedure platelet counts above
      270 * 10(3) /MUl were recruited among the blood center's apheresis donors. All
      complied with the center's donor selection criteria. RESULTS: One hundred
      fourteen (114) collections were performed. Depending on which definition of
      single platelet dose is used (2.0 * 10(11) as prevalent standard in most European
      countries, and 3.0 * 10(11) as prevalent standard in the United States and
      Canada) in 107/114 (single dose = 2.0 * 10(11) ) and 39/114 (single dose = 3.0 *
      10(11) ) instances, a triple platelet product was obtained. In 87 cases (76%), a
      double plasmaproduct (>430 ml) was collected, and in seven cases (6%), a single
      plasma product (>220 ml) was collected. In 20 procedures, only platelets without
      concurrent plasma were collected (18%). Overall procedure time was 87 +/- 13 min
      and average platelet yield per procedure was 8.5 +/- 1.4 * 10(11) (final storage
      concentration, 1,279 +/- 153 * 10(3) /MUl). The median residual leukocyte content
      per transfusion dose was 0.13 * 10(6) (0.02-0.98 * 10(6) ) for a single dose of
      2.0 * 10(11) and 0.14 * 10(6) (0.02-0.98 * 10(6) ) for a single dose of 3.0 *
      10(11) . CONCLUSIONS: Trima Accel(r) version 5.2 allows for collection of
      concentrated high yield platelet products. It offers high productivity and
      reliably achieves the configured yield targets. Leukoreduction performance
      complied with both US and EU legal requirements. Collection as hyperconcentrates
      furthermore allowed for concurrent collection of double dose plasma in the
      majority of the procedures.

PMID- 22362610
TI  - Any indication for bias due to participation? Comparison of the effects of a
      parent management training rated by participating and non-participating parents.
AB  - Ratings of parents that have participated in a parent training for child
      externalizing behaviour problems might be biased (e.g., they may report symptom
      reduction to reward their own endeavours for attending the training). The
      potential for bias in parent ratings was investigated in a secondary analysis of
      an effectiveness study of a parent management training for children (aged 3-10
      years) with externalizing behaviour problems under routine care conditions. For
      the 56 families included in the current analysis, we compared the ratings of
      training participants (predominately mothers) and training non-participants
      (predominately fathers). A 3-month waiting period prior to treatment served as
      the control condition. Outcome measures were attention problems and conduct
      problems of the children and perceived parental self-efficacy rated by both the
      mothers and fathers. Child attention problems and conduct problems both decreased
      significantly during the treatment period for participating and non-participating
      parents, and the changes in ratings during treatment were of a similar magnitude
      for participants compared with non-participants. Taking into account the
      methodological limitations of the current analysis, no indication was found that
      treatment effects are strongly biased due to participation in the training. KEY
      PRACTITIONER MESSAGES: Previous positive findings of mothers' and fathers'
      ratings on parent management training for children with externalizing problem
      behaviour have mostly come from parents who also attended the training. For child
      behavioural problems, the results of the current analysis demonstrate similar
      perceived changes by parents who did and did not participate in the training. Our
      findings underscore the relevance and importance of parent ratings for treatment
      evaluation.

PMID- 22362611
TI  - Sample size determination for quadratic inference functions in longitudinal
      design with dichotomous outcomes.
AB  - Quadratic inference functions (QIF) methodology is an important alternative to
      the generalized estimating equations (GEE) method in the longitudinal marginal
      model, as it offers higher estimation efficiency than the GEE when correlation
      structure is misspecified. The focus of this paper is on sample size
      determination and power calculation for QIF based on the Wald test in a marginal
      logistic model with covariates of treatment, time, and treatment-time
      interaction. We have made three contributions in this paper: (i) we derived
      formulas of sample size and power for QIF and compared their performance with
      those given by the GEE; (ii) we proposed an optimal scheme of sample size
      determination to overcome the difficulty of unknown true correlation matrix in
      the sense of minimal average risk; and (iii) we studied properties of both QIF
      and GEE sample size formulas in relation to the number of follow-up visits and
      found that the QIF gave more robust sample sizes than the GEE. Using numerical
      examples, we illustrated that without sacrificing statistical power, the QIF
      design leads to sample size saving and hence lower study cost in comparison with
      the GEE analysis. We conclude that the QIF analysis is appealing for longitudinal
      studies.

PMID- 22362612
TI  - Calibration and data processing in gas chromatography combustion isotope ratio
      mass spectrometry.
AB  - Compound-specific isotope analysis (CSIA) by gas chromatography combustion
      isotope ratio mass spectrometry (GCC-IRMS) is a powerful technique for the
      sourcing of substances, such as determination of the geographic or chemical
      origin of drugs and food adulteration, and it is especially invaluable as a
      confirmatory tool for detection of the use of synthetic steroids in competitive
      sport. We review here principles and practices for data processing and
      calibration of GCC-IRMS data with consideration to anti-doping analyses, with a
      focus on carbon isotopic analysis ((13)C/(12)C). After a brief review of peak
      definition, the isotopologue signal reduction methods of summation, curve
      fitting, and linear regression are described and reviewed. Principles for
      isotopic calibration are considered in the context of the Delta(13)C =
      delta(13)C(M) - delta(13)C(E) difference measurements required for establishing
      adverse analytical findings for metabolites (M) relative to endogenous (E)
      reference compounds. Considerations for the anti-doping analyst are reviewed.

PMID- 22362613
TI  - Enantioselective synthesis of beta-pyrazole-substituted alcohols through an
      asymmetric ring-opening reaction of meso-epoxides.
AB  - An efficient and practical synthesis of optically pure beta-pyrazole-substituted
      alcohols was achieved by an asymmetric ring-opening reaction of meso-epoxides
      with pyrazole derivatives as the nucleophile. In the presence of 1 mol % of an
      N,N'-dioxide-Sc(OTf)(3)  complex, excellent enantioselectivity and yields were
      obtained from meso-epoxides. The process could also be used for a mixture of cis-
      and trans-stilbene oxides. A proposed transition-state model is provided.

PMID- 22362614
TI  - Development of dipstick-based immuno-chemiluminescence techniques for the rapid
      detection of dichlorodiphenyltrichloroethane.
AB  - The occurrence of organochlorine pesticides in the environment has been a major
      concern, due to their high persistence and the possible impacts of their exposure
      to humans. Dichlorodiphenyltrichloroethane (DDT) is most hazardous and one of the
      most widely used organochlorine insecticides. DDT and its main metabolites are
      highly stable to physical, chemical and biological degradation and are therefore
      still being detected in many parts of the world. The present study describes
      dipstick-based immuno-chemiluminescence method for the detection of DDT with high
      sensitivity. Anti-DDT antibodies raised in chicken (IgY) were used as the
      biological sensing elements by immobilizing onto nitrocellulose membrane strips
      in a chemiluminescence (CL)-based dipstick technique. The photons generated
      during the biochemical interaction were directly proportional to the DDT
      concentration. A mean recovery of 81.2-95.6% was obtained for DDT-spiked fruit
      juice samples with 2.8-4.6% relative standard deviation (RSD). Using the proposed
      dipstick-based immuno-CL method, DDT was detected with linearity in the range
      0.05-1 ng/mL, having a limit of detection (LOD) of 0.05 ng/mL. This method can be
      used for the rapid, reliable detection of DDT pesticide.

PMID- 22362615
TI  - Multivalent gold glycoclusters: high affinity molecular recognition by bacterial
      lectin PA-IL.
AB  - Multivalent protein-carbohydrate interactions are involved in the initial stages
      of many fundamental biological and pathological processes through lectin
      carbohydrate binding. The design of high affinity ligands is therefore necessary
      to study, inhibit and control the processes governed through carbohydrate
      recognition by their lectin receptors. Carbohydrate-functionalised gold
      nanoclusters (glyconanoparticles, GNPs) show promising potential as multivalent
      tools for studies in fundamental glycobiology research as well as biomedical
      applications. Here we present the synthesis and characterisation of galactose
      functionalised GNPs and their effectiveness as binding partners for PA-IL lectin
      from Pseudomonas aeruginosa. Interactions were evaluated by hemagglutination
      inhibition (HIA), surface plasmon resonance (SPR) and isothermal titration
      calorimetry (ITC) assays. Results show that the gold nanoparticle platform
      displays a significant cluster glycoside effect for presenting carbohydrate
      ligands with almost a 3000-fold increase in binding compared with a monovalent
      reference probe in free solution. The most effective GNP exhibited a dissociation
      constant (K(d)) of 50 nM per monosaccharide, the most effective ligand of PA-IL
      measured to date; another demonstration of the potential of glyco-nanotechnology
      towards multivalent tools and potent anti-adhesives for the prevention of
      pathogen invasion. The influence of ligand presentation density on their
      recognition by protein receptors is also demonstrated.

PMID- 22362616
TI  - Psychological correlates of violent and non-violent Hong Kong juvenile
      probationers.
AB  - There is little known about Hong Kong juvenile offenders on probation. The
      purpose of this study was to compare Hong Kong juvenile violent with non-violent
      probationers on static demographic and psychological variables. The study
      comprised 109 male juvenile probationers aged 14-20 years (M = 16.97, SD = 1.44)
      in community transitional housing; 34 were adjudicated for violent offenses,
      while 75 were non-violent. The Rosenberg Self-Esteem Scale (RSES), Satisfaction
      with Life Scale (SWLS), Social Bonding Scale-Theft (SBS-T), Social Bonding Scale
      Violent Crime (SBS-VC), Positive and Negative Affect Scales (PANAS),
      Impulsiveness Scale-Short Form (IS-SF) and CRIME-PICS II were administered to
      measure self-esteem, life satisfaction, social bond, positive and negative
      affect, impulsivity, pro-offending attitudes, and self-perceived life problems.
      Data on onset age of delinquent behavior, age of first adjudication, number of
      prior adjudications, and frequency of self-reported delinquency in the past year
      were also collected. t-tests were consistent with significant differences for
      violent offenders including higher self-esteem (p < 0.05). Non-violent offenders
      self-reported significantly more theft (p < 0.05) with a tendency to deny victim
      hurt more often (p < 0.01); 76.5% of violent offenders self-reported both violent
      and non-violent crime, while 58.7% of non-violent offenders reported only non
      violent crime. For violent and non-violent offenders, the onset of delinquency
      was inversely related to the frequency of self-reported delinquency. Using
      ordinary least-squares (OLS) regression analyses, self-anticipated violent
      reoffending risk was predicted by age of onset, frequency of self-reported
      delinquency, social bond (inversely), and impulsivity, while non-violent
      reoffending risk was predicted by the number of prior convictions and self
      reported delinquency. Only two psychological correlates, social bond and
      impulsivity, were related to violent delinquency; interventions are suggested.

PMID- 22362617
TI  - Efficient designs of gene-environment interaction studies: implications of Hardy
      Weinberg equilibrium and gene-environment independence.
AB  - It is important to investigate whether genetic susceptibility variants exercise
      the same effects in populations that are differentially exposed to environmental
      risk factors. Here, we assess the power of four two-stage case-control design
      strategies for assessing multiplicative gene-environment (G-E) interactions or
      for assessing genetic or environmental effects in the presence of G-E
      interactions. We considered a di-allelic single nucleotide polymorphism G and a
      binary environmental variable E under the constraints of G-E independence and
      Hardy-Weinberg equilibrium and used the Wald statistic for all tests. We
      concluded that (i) for testing G-E interactions or genetic effects in the
      presence of G-E interactions when data for E are fully available, it is
      preferable to ascertain data for G in a subsample of cases with similar numbers
      of exposed and unexposed and a random subsample of controls; and (ii) for testing
      G-E interactions or environmental effects in the presence of G-E interactions
      when data for G are fully available, it is preferable to ascertain data for E in
      a subsample of cases that has similar numbers for each genotype and a random
      subsample of controls. In addition, supplementing external control data to an
      existing case-control sample leads to improved power for assessing effects of G
      or E in the presence of G-E interactions.

PMID- 22362618
TI  - Feedback-based alcohol interventions for mandated students: an effectiveness
      study of three modalities.
AB  - The present study used a randomized clinical trial design to examine the
      effectiveness of personalized alcohol feedback delivered individually, in a group
      and via computer on alcohol use and related negative consequences in a sample of
      173 college students referred for alcohol-related violations. Findings revealed
      statistically significant reductions in alcohol use and related harms for the
      individually delivered intervention, with significant reductions in alcohol
      related harms for the electronically delivered intervention. No statistically
      significant results were found for the group-delivered intervention or between
      groups, and a main effect of time was noted for all outcome variables. This study
      adds to the literature by being the first randomized clinical trial to include
      analyses of an empirically supported individually delivered personalized alcohol
      feedback intervention with more cost-effective group-delivered and electronically
      delivered feedback formats within a single research design, by expanding the
      range of participant drinking habits reported at baseline to include all drinking
      levels and not solely those classified as 'heavy drinking' and by providing
      anonymity pre-intervention and post-intervention given the potential demand
      characteristics to underreport illegal and/or illicit behaviours in this
      vulnerable population. KEY PRACTITIONER MESSAGE: Personalized alcohol feedback
      delivered in a one-on-one, face-to-face format serves to decrease both alcohol
      use and harms in mandated college students. The use of web-delivered personalized
      alcohol feedback may be clinically useful when working with a mandated student
      population to reduce alcohol-related harms. Personalized alcohol feedback
      delivered in a group setting may not be indicated for use with a mandated student
      population as it does not demonstrate decreases in either alcohol use or harms,
      possibly because of the normalization of deviant behaviour.

PMID- 22362620
TI  - In vivo testing of an intra-annular aortic valve annuloplasty ring in a chronic
      calf model.
AB  - OBJECTIVE: To increase applicability and stability of aortic valve repair, a
      three-dimensional aortic annuloplasty ring has been developed for intra-annular
      placement. The goal of this study was to test the safety of this device with in
      vivo implantation in the calf model. METHODS: In 10 chronic calves, the HAART
      annuloplasty ring was sutured to the aortic valve annulus using cardiopulmonary
      bypass. The animals were recovered and followed for 1-2 months. Serial
      echocardiography was used to evaluate valve competence, and contrast aortograms
      and CT angiograms were obtained in selected animals. After completion of follow
      up, each animal was euthanized, and aortic endoscopy was performed under water
      distension in five. Full autopsies with histologic examinations were performed.
      RESULTS: All animals survived surgery. Two were euthanized in the first week for
      complications, and the remaining eight calves were followed uneventfully for the
      1-2 months. Serial echocardiography showed completely competent valves in all but
      one animal, in which the ring was intentionally up-sized to test the sizing
      strategy. Contrast aortographic and CT angiographic findings were similar to the
      echocardiograms. Postmortem examination showed proper seating of all rings with
      endothelialization at 1-2 months. All valves demonstrated good leaflet coaptation
      and no abnormalities. CONCLUSIONS: In vivo testing of a three-dimensional aortic
      annuloplasty ring in a chronic calf model proved to be very successful and safe.
      Using the sizing and implant strategies developed, human trials seem indicated.

PMID- 22362621
TI  - Ectopic thymic tissue in the mediastinum: limitations for the operative treatment
      of myasthenia gravis.
AB  - OBJECTIVES: The aim of the study was to investigate the distribution of ectopic
      thymic tissue in the mediastinum and to evaluate the possible relevance of this
      distribution to the therapeutic yield of thymectomies in patients with myasthenia
      gravis. METHODS: In this prospective autopsy study, mediastinal dissections were
      performed on 50 cadavers without any previously known intrathoracic pathology.
      The initial dissection was performed in the same way as during the maximal
      thymectomy. The second stage consisted of dissecting areas of fatty tissue
      located out of reach of the standard maximal thymectomy, such as the perithyroid,
      periaortic, peritracheal and retrotracheal areas, as well as the areas adjacent
      to the right and left phrenic and recurrent laryngeal nerves. Each specimen was
      independently examined by two pathologists for ectopic thymic tissue. RESULTS:
      There were 41 (82%) male and 9 (18%) female cadavers, with a mean age of 44.3
      years (range: 15-75). Ectopic thymic tissue was detected in 32 out of 50 cadavers
      (64%). In 10 (20%) cadavers thymic foci were found in locations accessible to the
      standard surgical intervention and in 22 (44%)-in inaccessible locations. Thymic
      tissue incidence in individual locations was as follows: retrothyroid, 3 (6%);
      peritracheal, 5 (10%); retrotracheal, 1 (2%); right phrenic nerve, 2 (4%); left
      phrenic nerve, 14 (28%); right recurrent laryngeal nerve, 2 (4%); left recurrent
      laryngeal nerve, 2 (4%) and periaortic, 0. CONCLUSIONS: The incidence of ectopic
      thymic tissue in the mediastinum is common. Although some improvements in the
      results of thymectomies may be expected with more extensive dissection, the
      frequent presence of thymic foci in anatomical locations hardly accessible to
      surgical intervention may be the true limitation for surgical treatment of
      myasthenia.

PMID- 22362622
TI  - Limitations of open chest management.

PMID- 22362623
TI  - Transcaval invasion of right atrium by thymoma: resection via transient cava
      pulmonary shunt.
AB  - Transcaval extension of the thymoma to the right atrium has very rarely been
      reported, and cardiopulmonary bypass is recommended for successful resection. An
      invasive thymoma with intravascular invasion of the superior vena cava, and the
      left innominate vein extending into the right atrium was presented. Intra-atrial
      extension was resected through a transient external shunt from the inferior vena
      cava to the main pulmonary artery. We discussed the feasibility of this surgical
      technique and possible advantages of cardiopulmonary bypass avoidance.

PMID- 22362624
TI  - Does fast-tracking increase the readmission rate after pulmonary resection? A
      case-matched study.
AB  - OBJECTIVES: The most recent evolution of patient management after thoracic
      surgery implies the concept of fast-tracking. Since 2008, our unit has
      implemented a programme based on clinical protocols and standardized pathways of
      care aimed to reduce the postoperative stay after major lung resection. The
      objective of this study was to verify the safety of this policy by monitoring the
      patient readmission rate. METHODS: This is a prospective observational study on
      914 consecutive pulmonary lobectomies performed at our institution from January
      2000 to October 2010. Since we started the fast-tracking program in January 2008,
      we divided the patients into two groups: early period (678 patients, 2000-2007)
      and recent period (236 patients, 2008-October 2010). Several baseline and
      operative factors were used to build a propensity score that was applied to match
      the recent group patients with their early group counterparts. These two matched
      groups were then compared in terms of early outcomes and readmission rate.
      Readmission was defined as a re-hospitalization for any cause related to the
      operation within 30 days after discharge. We excluded from the analysis those
      patients with in-hospital mortality. RESULTS: Propensity score yielded 232 well
      matched pairs operated on in the early (non-fast-tracked patients) and most
      recent period (fast-tracked patients). The fast-tracking management resulted in a
      postoperative stay reduction of 2.8 days (P < 0.0001), with a 3-fold higher
      proportion of patients discharged before the sixth postoperative day (P <
      0.0001). Nevertheless, we did not observe any differences in terms of readmission
      rate between the two periods. CONCLUSIONS: In our experience, the implementation
      of a fast-tracking program after pulmonary lobectomy was very effective and safe.
      It led to a postoperative reduction of hospital stay without an increase in the
      readmission rate.

PMID- 22362625
TI  - Cannabis - from cultivar to chemovar.
AB  - The medicinal use of Cannabis is increasing as countries worldwide are setting up
      official programs to provide patients with access to safe sources of medicinal
      grade Cannabis. An important question that remains to be answered is which of the
      many varieties of Cannabis should be made available for medicinal use. Drug
      varieties of Cannabis are commonly distinguished through the use of popular
      names, with a major distinction being made between Indica and Sativa types.
      Although more than 700 different cultivars have already been described, it is
      unclear whether such classification reflects any relevant differences in chemical
      composition. Some attempts have been made to classify Cannabis varieties based on
      chemical composition, but they have mainly been useful for forensic applications,
      distinguishing drug varieties, with high THC content, from the non-drug hemp
      varieties. The biologically active terpenoids have not been included in these
      approaches. For a clearer understanding of the medicinal properties of the
      Cannabis plant, a better classification system, based on a range of potentially
      active constituents, is needed. The cannabinoids and terpenoids, present in high
      concentrations in Cannabis flowers, are the main candidates. In this study, we
      compared cultivars obtained from multiple sources. Based on the analysis of 28
      major compounds present in these samples, followed by principal component
      analysis (PCA) of the quantitative data, we were able to identify the Cannabis
      constituents that defined the samples into distinct chemovar groups. The study
      indicates the usefulness of a PCA approach for chemotaxonomic classification of
      Cannabis varieties.

PMID- 22362626
TI  - Mechanism of Pt(IV) sonochemical reduction in formic acid media and pure water.
AB  - Sonochemical synthesis of platinum nanoparticles (Pt NPs) in formic acid
      solutions and pure water was investigated using a 20 kHz ultrasonic irradiation.
      The obtained results gave new insights on the underneath Pt(IV)  reduction
      mechanism in formic acid media under argon and in pure water under Ar/CO
      atmosphere. It was shown that in pure water sonochemical reduction of platinum
      ions occurs by hydrogen issued from homolytic water molecule split. Pt(IV) ion
      reduction appears to be a very slow process under argon atmosphere in pure water
      due to formation of oxidizing species like OH radicals and H(2)O(2) leading to
      reoxidation of intermediate Pt(II)  ions. Sonochemical reduction is accelerated
      manifold in the presence of formic acid or Ar/CO gas mixture. Solution and gas
      phase analyses reveal that both CO and HCOOH act as OH(.) radical scavenger and
      reducing agent under ultrasonic irradiation. Their ability to reduce platinum
      ions at room temperature is enhanced due to the local heating in the liquid shell
      surround the cavitation bubble. An innovative synthesis route for monodispersed
      Pt NPs in pure water without any templates or capping agents in the presence of
      Ar/CO gas mixture is then proposed. Obtained Pt NPs within the range of 2-3 nm
      exhibited a strong stability towards sedimentation in water. Since Ar/CO
      atmosphere is the only restriction of the process, this procedure can be applied
      in various media and is also compatible with a large array of experimental
      conditions.

PMID- 22362627
TI  - One-step solvothermal synthesis of single-crystalline TiOF2 nanotubes with high
      lithium-ion battery performance.
AB  - Single-crystalline TiOF(2) nanotubes were prepared by a one-step solvothermal
      method. The nanotubes are rectangular in shape with a length of 2-3 MUm, width of
      200-300 nm, and wall thickness of 40-60 nm. The formation of TiOF(2) nanotubes is
      directly driven by the interaction between TiF(4) and oleic acid in octadecane to
      form the 1D nanorods, and this is followed by a mass diffusion process to form
      the hollow structures. The synthesis approach can be extended to grow TiOF(2)
      nanoparticles and nanorods. Compared with TiO(2), which is the more commonly
      considered anode material in lithium-ion batteries, TiOF(2) has the advantages of
      a lower Li-intercalation voltage (e.g., to help increase the total voltage of the
      battery cell) and higher specific capacities. The TiOF(2) nanotubes showed good
      Li-storage properties with high specific capacities, stable cyclabilities, and
      good rate capabilities.

PMID- 22362628
TI  - Genetic epidemiology and heritability of AIS: A study of 415 Chinese female
      patients.
AB  - Recent familial segregation studies supported a multifactorial genetic model for
      the etiology of adolescent idiopathic scoliosis (AIS). However, the extent of
      quantitative genetic effects, such as heritability, have not been fully
      evaluated. This genetic epidemiology study examined the sibling recurrent risk
      and heritability of AIS in first-degree relatives of 415 Chinese female patients,
      which is up to now the largest cohort. They were first diagnosed by community
      screening program and compared to 203 age-matched normal controls. Out of the
      total 531 sibs of AIS cases, 94 sibs had scoliosis (sibling recurrence risk =
      17.7%). The prevalence of AIS among male and female sibs of an index case were
      11.5% (95% CI = 7.5-15.5) and 23.0% (95% CI = 18.1-27.9), respectively. Female
      sibs of an index case had an increased risk of 8.9-fold (95% CI = 3.2-34.4) for
      developing AIS. These recurrent risks were significantly higher than the risk in
      the control group (p < 0.0001). Overall, heritability was estimated to be 87.5 +/
      11.1%. The results confirmed the prevailing impression of strong genetic
      influence on the risk of AIS. Here we provided a large-scale study for the
      genetic aggregation estimates in an Asian population for the first time. The
      finding also positioned AIS among other common disease or complex traits with a
      high heritability.

PMID- 22362629
TI  - Causal inference in epidemiological studies with strong confounding.
AB  - One of the identifiability assumptions of causal effects defined by marginal
      structural model (MSM) parameters is the experimental treatment assignment (ETA)
      assumption. Practical violations of this assumption frequently occur in data
      analysis when certain exposures are rarely observed within some strata of the
      population. The inverse probability of treatment weighted (IPTW) estimator is
      particularly sensitive to violations of this assumption; however, we demonstrate
      that this is a problem for all estimators of causal effects. This is due to the
      fact that the ETA assumption is about information (or lack thereof) in the data.
      A new class of causal models, causal models for realistic individualized exposure
      rules (CMRIER), is based on dynamic interventions. CMRIER generalize MSM, and
      their parameters remain fully identifiable from the observed data, even when the
      ETA assumption is violated, if the dynamic interventions are set to be realistic.
      Examples of such realistic interventions are provided. We argue that causal
      effects defined by CMRIER may be more appropriate in many situations,
      particularly those with policy considerations. Through simulation studies, we
      examine the performance of the IPTW estimator of the CMRIER parameters in
      contrast to that of the MSM parameters. We also apply the methodology to a real
      data analysis in air pollution epidemiology to illustrate the interpretation of
      the causal effects defined by CMRIER.

PMID- 22362630
TI  - Competition radioligand binding assays for the investigation of bispyridinium
      compound affinities to the human muscarinic acetylcholine receptor subtype 5
      (hM(5) ).
AB  - Standard treatment of poisoning by organophosphorus (OP) nerve agents with
      atropine and oximes lacks efficacy with some nerve agents. Promising in vitro and
      in vivo results were obtained with the bispyridinium compound SAD-128 which was
      partly attributed to its interaction with nicotinic acetylcholine receptors.
      Previous studies indicate that bispyridinium compounds interact with muscarinic
      acetylcholine receptors as well. The muscarinic M(5) receptor is not well
      investigated compared to other subtypes, but could be important in the search for
      new drugs for treating nerve agent poisoning. A set of bispyridinium compounds
      structurally related to SAD-128 were tested in competition binding experiments
      with recombinant human M(5) muscarinic acetylcholine receptors. Five of the six
      investigated bispyridinium compounds interacted with the orthosteric binding
      site, with affinities in the low micromolar range. These data indicate that
      interaction of bispyridinium compounds with muscarinic receptors may contribute
      to their therapeutic efficacy.

PMID- 22362631
TI  - A novel reddish-orange phosphor, NaLi2PO4:Eu3+.
AB  - A series of Eu(3+)-activated NaLi(2)PO(4) novel phosphors was synthesized by the
      solid-state reaction method. The X-ray diffraction (XRD) and photoluminescence
      (PL) properties of these phosphors were investigated at room temperature. The
      excitation spectra indicate that these phosphors can be effectively excited by
      near-UV (370-410 nm) light. The emission spectra exhibit strong reddish-orange
      performance, which is due to the (5)D(0) -> (7)F(J) transitions of Eu(3+) ions.
      The orange emission from transition (5)D(0) -> (7)F(1) is dominant over that of
      (5)D(0) -> (7)F(2.) The concentration quenching of Eu(3+) was observed in
      NaLi(2)PO(4):Eu(3+) when the Eu concentration was at 1 mol%. The impact of doping
      Eu(3+) and photoluminescence properties were investigated and we propose a
      feasible interpretation.

PMID- 22362632
TI  - Photocatalytic hydrogen evolution based on efficient energy and electron
      transfers in donor-bridge-acceptor multibranched-porphyrin-functionalized
      platinum nanocomposites.
AB  - Two donor-bridge-acceptor conjugates (5,10,15,20-tetrakis[4-(N,N
      diphenylaminobenzoate)phenyl] porphyrin (TPPZ) and 5,10,15,20-tetrakis[4-(N,N
      diphenylaminostyryl)phenyl] porphyrin (TPPX)) were covalently linked to
      triphenylamine (TPA) at the meso-position of porphyrin ring. The triphenylamine
      entities were expected to act as energy donors and the porphyrins to act as an
      energy acceptor. In this paper, we report on the synthesis of these multibranched
      porphyrin-functionalized Pt nanocomposites. The conjugates used here not only
      served as a stabilizer to prevent agglomeration of Pt nanoparticles, but also as
      a light-harvesting photosensitizer. The occurrence of photoinduced electron
      transfer processes was confirmed by time-resolved fluorescence and
      photoelectrochemical spectral measurements. The different efficiencies for energy
      and electron transfer in the two multibranched porphyrins and the functionalized
      Pt nanocomposites were attributed to diverse covalent linkages. Moreover, in the
      reduction of water to produce H(2), the photocatalytic activity of the Pt
      nanocomposite functionalized by TPPX, in which the triphenylamine and porphyrin
      moieties are bonded through an ethylene bridge, was much higher than that of the
      platinum nanocomposite functionalized by TPPZ, in which the two moieties are
      bonded through an ester. This investigation demonstrates the fundamental
      advantages of constructing donor-bridge-acceptor conjugates as highly efficient
      photosensitizers based on efficient energy and electron transfer.

PMID- 22362633
TI  - Hydrogen-bond-mediated asymmetric cascade reaction of stable sulfur ylides with
      nitroolefins: scope, application and mechanism.
AB  - A hydrogen-bond-mediated asymmetric [4+1] annulation/rearrangement cascade of
      stable sulfur ylides and nitroolefins was developed. This reaction provides a
      facile route to enantioenriched 4,5-substituted oxazolidinones in moderate to
      excellent isolated yields (65-96 %) with excellent stereocontrol (up to more than
      95:5 d.r. and 97:3 e.r.). This methodology was successfully applied to the
      concise synthesis of two bioactive molecules. The stereocontrolled modes and
      mechanism have been proposed to explain the origin of this stereochemistry.

PMID- 22362634
TI  - Chemiluminescence determination of gemifloxacin based on diperiodatoargentate
      (III)-sulphuric acid reaction in a micellar medium.
AB  - A novel flow-injection chemiluminescence (FI-CL) analysis method for the
      determination of gemifloxacin in the presence of cetyltrimethylammonium bromide
      (CTAB) surfactant micelles is described. Strong CL signal was generated during
      the reaction of gemifloxacin with diperiodatoargentate (III) in a sulfuric acid
      medium sensitized by CTAB. Under optimum experimental conditions, the CL
      intensity was linearly related to the concentration of gemifloxacin from 1.0 *
      10(-9) to 3.0 * 10(-7) g/mL and the detection limit was 7.3 * 10(-10) g/mL
      (3sigma). The relative standard deviation (RSD) was 1.7 % for a 3.0 * 10(-8) g/mL
      gemifloxacin solution (11 repeated measurements). The proposed method was
      successfully applied to the determination of gemifloxacin in pharmaceutical
      preparations and biological fluids. The possible mechanism of the CL reaction is
      also discussed briefly.

PMID- 22362635
TI  - Sensitivity analysis for unmeasured confounding in principal stratification
      settings with binary variables.
AB  - Within causal inference, principal stratification (PS) is a popular approach for
      dealing with intermediate variables, that is, variables affected by treatment
      that also potentially affect the response. However, when there exists unmeasured
      confounding in the treatment arms--as can happen in observational studies--causal
      estimands resulting from PS analyses can be biased. We identify the various
      pathways of confounding present in PS contexts and their effects for PS
      inference. We present model-based approaches for assessing the sensitivity of
      complier average causal effect estimates to unmeasured confounding in the setting
      of binary treatments, binary intermediate variables, and binary outcomes. These
      same approaches can be used to assess sensitivity to unknown direct effects of
      treatments on outcomes because, as we show, direct effects are operationally
      equivalent to one of the pathways of unmeasured confounding. We illustrate the
      methodology using a randomized study with artificially introduced confounding and
      a sensitivity analysis for an observational study of the effects of physical
      activity and body mass index on cardiovascular disease.

PMID- 22362636
TI  - Hepatoblastoma--an attempt of histological subtyping on fine-needle aspiration
      material.
AB  - Hepatoblastoma (HB) is classified into epithelial, mixed
      (epithelial/mesenchymal), and small-cell (anaplastic) type. Wnt/beta-catenin
      pathway plays a key role in hepatic development, regeneration, and tumorigenesis,
      and HB is known to present beta-catenin mutations (50-90%). The present study was
      undertaken to delineate the cytomorphologic features of HB and to evaluate the
      feasibility of subtyping of HB on fine-needle aspiration cytology (FNAC). The
      expression of beta-catenin in these tumors was also evaluated both of
      histopathologic sections and on the aspirated material. Thirty-three cases with
      fine-needle aspirates of HB were retrieved over a period of 12 years. Cytologic
      diagnosis was reviewed in the light of clinicoradiological data, response to
      therapy, and subsequent histopathology. Immunochemistry for beta-catenin was
      performed in 19 of 33 cases on histopathologic sections (n = 10)/cell blocks (n =
      6)/cytosmears (n = 3). Based on the cytologic features, the cases were divided
      into fetal HB (n = 17), embryonal HB (n = 4), combined epithelial HB (n = 8), and
      mixed HB (n = 4). Four cases of histopathologically proven mixed HB were reported
      as pure epithelial HB on FNAC, as mesenchymal elements were not represented in
      the cytology smears. Cytoplasmic as well as nuclear staining for beta-catenin was
      noted in a total of 10 of 19 cases. FNAC can accurately categorize epithelial HB;
      however, in mixed type, the accuracy depends on number of areas sampled. Cell
      block can be of help to perform ancillary investigations especially beta-catenin
      for both diagnostic and therapeutic purposes.

PMID- 22362637
TI  - Retrospective image correction in the presence of nonlinear temporal magnetic
      field changes using multichannel navigator echoes.
AB  - Spatio-temporal magnetic field changes in the brain caused by breathing or body
      movements can lead to image artifacts. This is especially a problem in T(2)(*)
      weighted sequences. With the acquisition of an extra echo (navigator), it is
      possible to measure the magnetic field change induced frequency offset for a
      given slice during image acquisition. However, substantial local variation across
      a slice can occur. This work describes an extension of the conventional navigator
      technique that improves the estimation of the magnetic field distribution in the
      brain during strong field fluctuations. This is done using the combination of
      signals from multiple coil elements, the coil sensitivity profiles, and frequency
      encoding: termed sensitivity-encoded navigator echoes. In vivo validation was
      performed in subjects who performed normal breathing, nose touching, and deep
      breathing during scanning. The sensitivity-encoded navigator technique leads to
      an error reduction in estimating the field distribution in the brain of 73% +/-
      16% compared with 56% +/- 14% for conventional estimation. Image quality can be
      improved via incorporating this navigator information appropriately into the
      image reconstruction. When the sensitivity-encoded navigator technique was
      applied to a T(2)(*)-weighted sequence at 7 T, a ghosting reduction of 47% +/-
      13% was measured during nose touching experiments compared with no correction.

PMID- 22362638
TI  - A systematic review of risk factors associated with transitioning from regional
      musculoskeletal pain to chronic widespread pain.
AB  - Chronic widespread pain has limited treatment options and is associated with
      pronounced negative individual and socioeconomic consequences. Patients with
      local or regional pain may be at a risk for developing chronic widespread pain.
      Knowledge of such risk factors can help prevent chronic widespread pain. This
      study systematically reviews the literature that examines risk factors associated
      with developing chronic widespread after developing chronic regional pain. We
      conducted a three-step database search in Medline. Four articles from the
      authors' files formed a core set of articles that were used to validate the
      search strategy. We conducted a systematic quality assessment of the included
      studies. Based on risk estimations reported in six prospective population-based
      studies and one retrospective study on pain, this study identified five risk
      factors: female sex, higher age, family history of pain, depressed mode and pain
      sites at baseline. As only a few studies were recovered, the impact of these
      factors is unclear. Spreading of pain from local or regional pain to widespread
      pain occurs in a large proportion of the general population. Few studies have
      addressed similar risk factors and the few risk factors associated with the
      transition from chronic regional pain to chronic widespread pain are
      inconsistent. Studies that focus on this transition have included few subjects
      and few possible risk factors. Future studies should explore more possible risk
      factors.

PMID- 22362639
TI  - The structures, morphologies, and photophysical properties of multiluminescent
      layered lanthanide-phosphono-carboxylate nanoparticles.
AB  - A new family of layered metal(III)-phosphono-carboxylate nanostructures (M=Y, Eu,
      Tb, Er, and Yb) was hydrothermally synthesized and their structures and
      morphologies were characterized by X-ray powder diffraction and TEM. 4
      [Bis(phosphonomethyl)amino]caproic acid and 4-
      [bis(phosphonomethyl)amino]undecanoic acid, with general formula
      (H(2)O(3)PCH(2))(2)NR (R=C(5)H(10)COOH(P2CAPR) and C(10)H(22)COOH(P2UND),
      respectively) were used as building blocks for the preparation of novel layered
      hybrid materials in which the inorganic layers were composed of MO(7) or MO(8)
      polyhedra and PO(3)C tetrahedra. The interlayer region was occupied by
      carboxyalkyl chains. These layered compounds were easily dispersed as stable
      solutions in alkylamine/water upon ultrasonication. These dispersions were
      constituted of rectangular elongated nanoparticles (NPs), which showed a
      distribution of sizes ranging from 20-500 nm. These new materials had interesting
      photophysical properties because they were multiluminescent compounds. These
      properties gave rise to several emission bands, which were spread over the broad
      spectroscopic region, from the near-UV up to the near-IR regions. Each emission
      band had a specific lifetime, which ranged from the sub-ps to the ms scale.

PMID- 22362640
TI  - Effects of dehydration on immune functions after a judo practice session.
AB  - We investigated the effects of dehydration after a judo practice session on
      player muscle and immune functions. Subjects included 25 female university
      judoists. Investigations were performed before and after 2.5 h of regular judo
      practice. Body composition, serum enzymes (myogenic enzymes, immunoglobulins and
      complements), neutrophils counts, reactive oxygen species (ROS) production
      capability, and phagocytic activity (PA) were measured. Subjects were divided
      into two groups according to level of dehydration after practice (mild
      dehydration and severe dehydration groups) and results were compared. Creatine
      kinase was found to increase significantly after practice. In addition,
      neutrophil count also increased significantly after practice in both groups. The
      changing ratios of IgA, IgG and C3 observed in the mild dehydration group were
      significantly higher than those in the severe dehydration group. In the severe
      dehydration group, post-practice PA/neutrophil had decreased significantly.
      Significant positive correlations were found between severity of dehydration and
      changing ratios of IgA, IgG, IgM, C3, C4 and ROS production capabilities, whereas
      no significant association was seen with PA and/or serum SOD activity. These
      results suggest that dehydration resulted in immunosuppression, including
      decreased neutrophil function.

PMID- 22362641
TI  - Dyshormonogenetic goiter-like changes in a child with congenital hypothyroidism
      and a euthyroid adult.
AB  - Dyshormonogenetic goiter is a rare entity that presents in patients who typically
      have a history of congenital hypothyroidism, and generally arises from a genetic
      mutation compromising the production of functional thyroxine or thyroglobulin.
      Clinically, physical manifestations of goiter can result if left untreated.
      Histologically, the thyroid lesions usually show prominent bridging fibrosis,
      multiple thyroid nodules with different architectures, microfollicular
      arrangement, scant colloid, and enlarged vesicular or hyperchromatic nuclei.
      Cytologically, the features of the lesion are not distinguishable from follicular
      lesion and follicular neoplasm. We describe two patients exhibiting similar
      histological and cytological features resembling dyshormonogenetic goiter with
      cytologic misinterpretation as follicular neoplasm. One was a child with an
      established history of congenital hypothyroidism. The other was an adult
      euthyroid patient who presented with an associated parathyroid adenoma. These
      findings further affirm that cytologically and histologically, morphologic
      features associated with dyshormonogenetic goiter can also be found in patients
      without a history of congenital hypothyroidism.

PMID- 22362642
TI  - Up-front versus sequential randomizations for inference on adaptive treatment
      strategies.
AB  - Adaptive treatment strategies are useful in the treatment of chronic diseases
      such as AIDS and cancer because they allow tailoring the treatment to a patient's
      need and disease status. We consider two randomization schemes for clinical
      trials that are commonly used to design studies comparing adaptive treatment
      strategies, namely, up-front randomization and sequential randomization. Up-front
      randomization is the classical method of randomization where patients are
      randomized at the beginning of the study to pre-specified treatment strategies.
      In sequentially randomized trials, patients are randomized sequentially to
      available treatment options over the duration of the therapy as they become
      eligible to receive subsequent treatments. We compare the efficiency and the
      power of the traditional up-front randomized trials with that of sequentially
      randomized trials designed for comparing adaptive treatment strategies based on a
      continuous outcome. The analytical and simulation results indicate that, when
      properly analyzed, sequentially randomized trials are more efficient and powerful
      than up-front randomized trials.

PMID- 22362643
TI  - Characterization and mapping of dipolar interactions within macromolecules in
      tissues using a combination of DQF, MT and UTE MRI.
AB  - This study shows that by combining a double-quantum filtered magnetization
      transfer (DQF-MT) with an ultra-short TE (UTE) MRI that it is possible to obtain
      contrast between tissue compartments based on the following characteristics: (a)
      the residual dipolar coupling interaction within the biomacromolecules, which
      depends on their structure, (b) residual dipolar interactions within water
      molecules, and (c) the magnetization exchange rate between biomacromolecules and
      water. The technique is demonstrated in rat-tail specimens, where the collagenous
      tissue such as tendons and the annulus pulposus of the disc are highlighted in
      these images, and their macromolecular properties along with those of bones and
      muscles can be characterized. DQF-MT UTE MRI also holds promise because
      collagenous tissues that are typically invisible in conventional MRI experiments
      produce significant signal intensities using this approach.

PMID- 22362644
TI  - An evaluation of students' perceptions of a college-based programme that involves
      patients, carers and service users in physiotherapy education.
AB  - BACKGROUND: There is little evidence of the integration of UK physiotherapy
      university education into clinical practice, and some students say that they are
      not adequately prepared for professional life. This was addressed by a college
      based programme involving patients, carers and service users as facilitators of
      learning to enhance the partnership between health professionals and patients.
      PURPOSE: This programme has been running for 2 years, and this paper is an
      evaluation of the students' perceptions of it, appraising the outcomes of their
      learning in order to discover the ways in which it can be enhanced, improved or
      changed. METHODS: A grounded theory approach utilizing focus groups and semi
      structured interviews was conducted. Three focus groups representing the higher
      educational levels 4-6 in pre-registration physiotherapy were carried out.
      Following the analysis of the focus groups, seven interviews reflecting the three
      educational levels were conducted in order to explore in greater depth the
      findings from the focus groups. The analysis of the focus groups and the
      subsequent interviews were carried out in accordance with a grounded theory
      framework. RESULTS: The students perceived the programme as a context in which to
      think how their learning needs could be met within a 'real' framework but on
      their own territory. Equally, it created feelings of anxiety at being given such
      an open forum that created a challenge to their communication skills. Many
      expressed a wish for a more explicit mentoring-learning environment. They also
      perceived a tension between the technical-rational demands of academia and social
      practice and a need to view this as a basis for critical appraisal and self
      awareness. CONCLUSION: This programme appeared to be integral to the students'
      development as future physiotherapists.

PMID- 22362645
TI  - Changes in neutrophil functions during a 10-month soccer season and their effects
      on the physical condition of professional Japanese soccer players.
AB  - We examined changes in neutrophil function of soccer players over a 10-month
      period and determined its effectiveness as an index for athlete physical
      condition. Subjects included 21 male professional Japanese soccer players. Data
      on body composition, myogenic enzymes and neutrophil function were obtained
      before and after 2 h of training at 3 investigation points: one week before
      opening season, at season mid-point, and one week before the last game of the
      season. As a result, change ratios of myogenic enzyme levels before and after the
      2-hr training session at the third investigation point were significantly higher
      compared to the two other points. Reactive oxygen species production and
      phagocytic activity significantly increased after 2-hr training session at point
      1, although the extent of the increase became smaller over time and ROS
      production capability decreased significantly by point 3 assessment. Fatigue,
      especially muscle fatigue, chronically accumulated along with a gradual decrease
      in neutrophil immune function over the 10-month season. Therefore, determination
      of neutrophil function can be used as a useful index to assess and understand an
      athlete's physical condition.

PMID- 22362646
TI  - Osteoid in cellblock sections of ascitic fluid: a clue for the diagnosis of
      hepatoblastoma.

PMID- 22362647
TI  - New hyperbranched polytriazoles containing isolation chromophore moieties derived
      from AB4 monomers through click chemistry under copper(I) catalysis: improved
      optical transparency and enhanced NLO effects.
AB  - By modifying a synthetic procedure, two new hyperbranched polytriazoles (HP1 and
      HP2) containing isolation chromophores were synthesized successfully through
      click chemistry reactions under copper(I) catalysis. For the first time, these
      two polymers were derived from an AB(4)-type monomer, although they contain
      different end-capping chromophores. They are soluble in normal polar organic
      solvents and are well characterized. Thanks to the presence of the isolation
      chromophore, the two polymers demonstrate good nonlinear optical (NLO) properties
      and optical transparency, making them promising candidates for practical
      applications.

PMID- 22362648
TI  - An analysis of predictive markers for intracranial haemorrhage in warfarinised
      head injury patients.
AB  - INTRODUCTION: Minor head injury in older patients on warfarin may present in a
      variety of ways that often fall outside the remit of conventional guidelines. The
      aim of this study was to determine the relative risks for intracranial
      haemorrhage (ICH) in patients with subtherapeutic, therapeutic and
      supratherapeutic INR levels, in addition to the relative risks for the common
      symptoms at presentation. METHODS: The notes were retrospectively reviewed of all
      patients who had a CT scan requested by the emergency department over a 2-year
      period (January 2008 to December 2009) and from these warfarinised head injuries
      were identified. RESULTS: 82 warfarinised head injury patients were identified
      from 3338 requested CT scans. 12 of these patients (15%) had evidence of ICH on
      the CT. 72 patients had their INR checked (88%) and the RR of ICH for the INR
      subgroups were calculated: INR <2 (RR 1.89; 95% CI 0.65 to 5.55); INR 2-3 (RR
      0.84; 95% CI 0.27 to 2.64); and INR >3 (RR 0.53; 95% CI 0.13 to 2.29). The
      greatest proportion of those with ICH (42%) had a subtherapeutic INR. 2 out of
      the 12 patients (17%) were found to have intracranial bleeding despite not
      meeting the criteria for a CT scan according to the NICE guidelines. CONCLUSION:
      The results of the INR subgroup analysis suggest that a subtherapeutic INR may
      not be protective against ICH in patients with minor head injury.

PMID- 22362649
TI  - Major trauma and urban cyclists: physiological status and injury profile.
AB  - INTRODUCTION: Pedal cycling in cities has the potential to deliver significant
      health and economic benefits for individuals and society. Safety is the main
      concern for potential cyclists although the statistical risk of death is low.
      Little is known about the severity of injuries sustained by city cyclists and
      their outcome. AIM: The aim of this study was to characterise the physiological
      status and injury profile of cyclists admitted to our urban major trauma centre
      (MTC). METHODS: Database analysis of cyclist casualties between 2004 and 2009.
      The physiological parameters examined were admission systolic blood pressure
      (SBP), admission base deficit and prehospital Glasgow Coma Scale. RESULTS: 265
      cyclists required full trauma-team activation. 82% were injured during a
      collision with a motorised vehicle. The majority (73%) had collided with a car or
      a heavy goods vehicle (HGV). These casualties formed the cohort for further
      analysis. Cyclists who collided with an HGV were more severely injured and had a
      higher mortality rate. Low SBP and high base deficit indicate that haemorrhagic
      shock is a key feature of HGV casualties. CONCLUSION: Collision with any vehicle
      can result in death or serious injury to a cyclist. Injury patterns vary with the
      type of vehicle involved. HGVs were associated with severe injuries and death as
      a result of uncontrollable haemorrhage. Awareness of this injury profile may aid
      prehospital management and expedite transfer to MTC care. Rapid haemorrhage
      control may salvage some, but not all, of these casualties. The need for
      continued collision prevention strategies and long-term outcome data collection
      in trauma patients is highlighted.

PMID- 22362650
TI  - Accuracy of the initial diagnosis among patients with an acutely altered mental
      status.
AB  - OBJECTIVES: The objectives of this prospective observational study were to: (1)
      determine the accuracy of physician diagnosis in patients with an acutely altered
      mental status (AMS) within the first 20 min of emergency department (ED)
      presentation; and (2) access if physician confidence in early diagnosis
      correlates with accuracy of diagnosis. METHODS: A prospective observational
      convenience study was conducted of 112 adult patients who presented to an urban
      county ED with AMS (Glasgow Coma Scale (GCS) score <=14) between August 2008 and
      July 2009. Within the first 20 min of patient presentation to the ED, treating
      physicians were asked to record their best diagnostic guess of the cause of the
      patient's AMS and their confidence in this diagnosis. Serial hourly GCS was
      performed and the results of all diagnostic testing were recorded. Blinded
      investigators determined the final consensus diagnostic cause of the patient's
      AMS. RESULTS: The final consensus diagnoses for AMS aetiologies were as follows:
      isolated alcohol intoxication 31%, other (psychotic episodes, underlying
      dementia) 21%, combination alcohol/other drug intoxications 18%, isolated other
      drug intoxications 10%, other metabolic derangements 6%, cerebrovascular
      accident/transient ischaemic attack 4%, seizures/post-ictal states 4%, traumatic
      brain injuries 3%, isolated opiate intoxications 2%, isolated benzodiazepine
      intoxication 1% and septic episode 1%. The emergency physician's initial
      diagnosis of the AMS patient correlated with the accuracy of the final diagnosis
      (r(2)=0.807). The quintiles of confidence of diagnosis were: 0-20% degree of
      confidence had a 33% diagnostic accuracy, 21-40% had 25% accuracy, 41-60% had 43%
      accuracy, 61-80% had 52% accuracy and those with 81-100% confidence of initial
      diagnosis had 78% accuracy. Of the 106 patients with an initial diagnosis, 52
      (51%) had a head CT performed, with eight (8%) having an acute abnormality.
      DISCUSSION: Early diagnoses of AMS patients are moderately accurate. Few early
      misdiagnoses of AMS patients were clinically relevant. Physicians' greater degree
      of confidence in their diagnosis correlated with greater accuracy.

PMID- 22362651
TI  - Highly homogeneous stereocontrolled construction of quaternary hydroxyesters by
      addition of dimethylzinc to alpha-ketoesters promoted by chiral
      perhydrobenzoxazines and B(OEt)3.
AB  - A highly efficient enantioselective addition of Me(2)Zn to alpha-ketoesters,
      assisted by a chiral perhydro-1,3-benzoxazine ligand, is described. This novel
      catalytic system offers homogeneous elevated enantioselectivities in the
      preparation of alpha-hydroxyesters that bear a quaternary stereocenter, with a
      minor dependence on electronic and steric effects when aromatic, heteroaromatic,
      or aliphatic alpha-ketoesters are employed. The catalyst can be recovered and
      reused without loss of activity.

PMID- 22362652
TI  - Characterization of a single gene cluster responsible for methylpendolmycin and
      pendolmycin biosynthesis in the deep sea bacterium Marinactinospora
      thermotolerans.
AB  - The nine-membered indolactam antibiotics belong to a small group of antibiotics
      showing broad biological activities. However, the in vivo genetic engineering of
      compounds of this type has not been performed. Here we report the identification
      of a single gene cluster responsible for the biosynthesis of methylpendolmycin
      and pendolmycin, two members of this family of antibiotics, from the deep sea
      bacterium Marinactinospora thermotolerans SCSIO 00652. Bioinformatics analysis
      and gene inactivation, coupled with metabolite characterization, reveal that
      MpnB, a nonribosomal peptide synthetase, MpnC, a cytochrome P450, and MpnD, a
      prenyltransferase, are sufficient to catalyze the biosynthesis of the two
      antibiotics from L-Ile (or L-Val), L-Trp, and methionine. MpnD is the first
      identified enzyme that transfers a C5 prenyl unit in a reverse manner to the C-7
      position of a Trp-derived natural product.

PMID- 22362653
TI  - Amyloidomas of soft parts: diagnosis by fine-needle aspiration.
AB  - A tumoral mass of amyloid (amyloidoma) arising in the soft tissues of the distal
      extremities is exceedingly unusual, and applying the fine-needle aspiration (FNA)
      biopsy technique to specifically diagnose this condition is even more infrequent.
      Herein, we report an example of two separate amyloidomas arising in the right
      calf of an otherwise asymptomatic elderly man who was referred to the sarcoma
      clinic because these masses clinically and radiographically simulated a malignant
      neoplasm. The fine-needle aspirate yielded amorphous, acellular, dense blue
      material on Romanowsky-stained smears and smudgy acellular cyanophilic material
      on Papanicolaou-stained smears. The aspirate procured cell-block contained
      hyalinized eosinophilic acellular material on H&E stain that was Congo-red
      positive and displayed yellow-green birefringence with polarization. Unlike prior
      assertions to the contrary, a diagnosis of amyloidoma is possible using FNA
      cytopathology even in patients without a known underlying amyloidogenic disorder.

PMID- 22362654
TI  - Quantification of MRI signal of transgenic grafts overexpressing ferritin in
      murine myocardial infarcts.
AB  - The noninvasive detection of transplanted cells in damaged organs and the
      longitudinal follow-up of cell fate and graft size are important for the
      evaluation of cell therapy. We have shown previously that the overexpression of
      the natural iron storage protein, ferritin, permits the detection of engrafted
      cells in mouse heart by MRI, but further imaging optimization is required. Here,
      we report a systematic evaluation of ferritin-based stem cell imaging in
      infarcted mouse hearts in vivo using three cardiac-gated pulse sequences in a 3-T
      scanner: black-blood proton-density-weighted turbo spin echo (PD TSE BB), bright
      blood T(2) -weighted gradient echo (GRE) and black-blood T(2) -weighted GRE with
      improved motion-sensitized-driven equilibrium (iMSDE) preparation. Transgenic
      C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the
      PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black
      blood T(2) -weighted iMSDE (p < 0.05) and a 30% reduction in bright-blood T(2) 
      weighted GRE (p < 0.0001). Graft size measurements by T(2) iMSDE and T(2) GRE
      were highly correlated with histological assessments (r = 0.79 and r = 0.89,
      respectively). Unlabeled wild-type C2C12 cells transplanted to mouse heart did
      not change the MRI signal intensity, although endogenous hemosiderin was seen in
      some infarcts. These data support the use of ferritin to track the survival,
      growth and migration of stem cells transplanted into the injured heart.

PMID- 22362655
TI  - Using R and WinBUGS to fit a generalized partial credit model for developing and
      evaluating patient-reported outcomes assessments.
AB  - The US Food and Drug Administration recently announced the final guidelines on
      the development and validation of patient-reported outcomes (PROs) assessments in
      drug labeling and clinical trials. This guidance paper may boost the demand for
      new PRO survey questionnaires. Henceforth, biostatisticians may encounter
      psychometric methods more frequently, particularly item response theory (IRT)
      models to guide the shortening of a PRO assessment instrument. This article aims
      to provide an introduction on the theory and practical analytic skills in fitting
      a generalized partial credit model (GPCM) in IRT. GPCM theory is explained first,
      with special attention to a clearer exposition of the formal mathematics than
      what is typically available in the psychometric literature. Then, a worked
      example is presented, using self-reported responses taken from the international
      personality item pool. The worked example contains step-by-step guides on using
      the statistical languages r and WinBUGS in fitting the GPCM. Finally, the Fisher
      information function of the GPCM model is derived and used to evaluate, as an
      illustrative example, the usefulness of assessment items by their information
      contents. This article aims to encourage biostatisticians to apply IRT models in
      the re-analysis of existing data and in future research.

PMID- 22362657
TI  - Intrathecal application of autologous bone marrow cell preparations in
      Parkinsonian syndromes.
AB  - BACKGROUND: A growing number of patients is treated with intrathecal application
      of autologous bone marrow cells (aBMCs), but clinical data are completely lacking
      in movement disorders. We provide first clinical data on efficacy and safety of
      this highly experimental treatment approach in parkinsonian syndromes. METHODS:
      Retrospective data collection from patients with parkinsonism who spontaneously
      sought cell treatment. The application procedure was neither recommended nor
      performed by the authors. RESULTS: We report 17 patients with parkinsonian
      syndromes (Parkinson's disease [PD], n = 7; multiple system atrophy [MSA], n = 7;
      various, n = 3) who received intrathecal application of aBMCs. We did not observe
      any changes in motor function, activities of daily living, global clinical
      impression, or antiparkinsonian medication after a median observation period of
      10 months. Two patients reported a worsening of parkinsonian symptoms, but the
      intervention was otherwise safe and well-tolerated. CONCLUSIONS: Intrathecal
      application of aBMCs in uncontrolled conditions produces no clinical benefit in
      parkinsonian syndromes.

PMID- 22362656
TI  - Enzymatic activity of albumin shown by coelenterazine chemiluminescence.
AB  - Bioluminescence, the emission of light from live organisms, occurs in 18 phyla
      and is the major communication system in the deep sea. It has appeared
      independently many times during evolution but its origins remain unknown.
      Coelenterazine bioluminescence discovered in luminous jellyfish is the most
      common chemistry causing bioluminescence in the sea, occurring in seven phyla.
      Sequence similarities between coelenterazine luciferases and photoproteins from
      different phyla are poor (often < 5%). The aim of this study was to examine
      albumin that binds organic substances as a coelenterazine luciferase to test the
      hypothesis that the evolutionary origin of a bioluminescent protein was the
      result of the formation of a solvent cage containing just a few key amino acids.
      The results show for the first time that bovine and human albumin catalysed
      coelenterazine chemiluminescence consistent with a mono-oxygenase, whereas
      gelatin and haemoglobin, an oxygen carrier, had very weak activity. Insulin also
      catalysed coelenterazine chemiluminescence and was increased by Zn(2+). Albumin
      chemiluminescence was heat denaturable, exhibited saturable substrate
      characteristics and was inhibited by cations that bound these proteins and by
      drugs that bind to human albumin drug site I. Molecular modelling confirmed the
      coelenterazine binding site and identified four basic amino acids: lys195,
      arg222, his242 and arg257, potentially important in binding and catalysis similar
      to naturally occurring coelenterazine bioluminescent proteins. These results
      support the 'solvent cage' hypothesis for the evolutionary origin of enzymatic
      coelenterazine bioluminescent proteins. They also have important consequences in
      diseases such as diabetes, gut disorders and food intolerance where a mono
      oxygenase could affect cell surface proteins.

PMID- 22362658
TI  - Synthesis and reactivity of 5,10,15-triaryl doubly N-confused bilanes.
AB  - A series of 5,10,15-tris(pentafluorophenyl) doubly N-confused bilanes were
      synthesized in a stepwise manner with the aid of sterically demanding N
      protecting groups, in which the difference in reactivity between regular pyrrole
      and N-confused pyrrole plays a crucial role in the synthetic strategy. Some
      doubly N-confused bilanes were converted into porphyrinoids or a unique 2:2
      copper(II) complex with a helical structure. In addition, the conformations and
      electronic states of the doubly N-confused bilanes were investigated
      theoretically, giving fruitful information about the effect of confusion on the
      bilane skeleton.

PMID- 22362659
TI  - Identification of a novel protein synthesis inhibitor active against gram
      positive bacteria.
AB  - In an effort to identify novel antibacterial chemotypes, we performed a whole
      cell screen for inhibitors of Staphylococcus aureus growth and pursued those
      compounds with previously uncharacterized antibacterial activity. This process
      resulted in the identification of a benzothiazolium salt, ABTZ-1, that displayed
      potent antibacterial activity against Gram-positive pathogens. Several clinically
      desirable qualities were demonstrated for ABTZ-1 including potent activity
      against multidrug-resistant clinical isolates of methicillin-resistant S. aureus
      (MRSA) and vancomycin-resistant enterococci (VRE), retention of this activity in
      human serum, and low hemolytic activity. The antibacterial activity of ABTZ-1 was
      attributed to its inhibition of bacterial translation, as this compound prevented
      the incorporation of [35S]methionine into S. aureus proteins, and ABTZ-1
      resistant strains were cross-resistant to known inhibitors of bacterial
      translation. ABTZ-1 represents a promising new class of antibacterial agents.

PMID- 22362660
TI  - Cytogenetic and molecular evidence suggest multiple origins and geographical
      parthenogenesis in Nothoscordum gracile (Alliaceae).
AB  - BACKGROUND AND AIMS: Nothoscordum gracile is an apomitic tetraploid widely
      distributed throughout the Americas and naturalized in many temperate regions of
      other continents. It has been suggested to form a species complex with sexual and
      apomictic N. nudicaule and N. macrostemon. Tetraploids of these species also
      share a structurally heterozygous chromosome complement 2n = 19 (13M + 6A). In
      this work, the origin of N. gracile and its relationships with its related
      species was investigated based on cytological and molecular data. METHODS:
      Cytogenetic analyses were based on meiotic behaviour, CMA bands, localization of
      5S and 45S rDNA sites, and genomic in situ hybridization (GISH). Nuclear ITS and
      plastidial trnL-trnF sequences were also obtained for most individuals. KEY
      RESULTS: Proximal CMA bands were observed in the long arms of all acrocentrics of
      2x and 4x N. macrostemon but not in diploid and some tetraploid cytotypes of N.
      nudicaule. Samples of N. gracile showed a variable number of CMA bands in the
      long arms of acrocentrics. Analysis of ITS sequences, dot-blot, GISH, and 5S and
      45S rDNA sites, revealed no differentiation among the three species. The trnL
      trnF cpDNA fragment showed variation with a trend to geographical structuring
      irrespective of morphospecies and fully congruent with karyotype variation.
      CONCLUSIONS: The 2n = 19 karyotype was probably formed by a centric fusion event
      occurring in N. nudicaule and later transmitted to tetraploid cytotypes of N.
      macrostemon. Diploids of N. nudicaule and N. macrostemon appeared as consistent
      recently diverged species, whereas tetraploid apomicts seem to constitute an
      assemblage of polyploid hybrids originating from multiple independent
      hybridization events between them, part of which are morphologically recognizable
      as N. gracile.

PMID- 22362661
TI  - Sympatric species of Hibbertia (Dilleniaceae) vary in dormancy break and
      germination requirements: implications for classifying morphophysiological
      dormancy in Mediterranean biomes.
AB  - BACKGROUND AND AIMS: Several ecologically important plant families in
      Mediterranean biomes have seeds with morphophysiological dormancy (MPD) but have
      been poorly studied. The aim of this study was to understand the seed ecology of
      these species by focusing on the prominent, yet intractably dormant Australian
      genus Hibbertia. It was hypothesized that the slow germination in species of this
      genus is caused by a requirement for embryo growth inside the seed before
      germination, and that initiation of embryo growth is reliant upon a complex
      sequence of environmental cues including seasonal fluctuations in temperature and
      moisture, and an interplay with light and smoke. Using the results, the
      classification of the MPD level in species of Hibbertia is considered. METHODS:
      Four species of Hibbertia in winter rainfall south-western Australia were
      selected. These species, whilst differing in geographic distributions, are
      variously sympatric, and all are important understorey components of plant
      communities. The following aspects related to dormancy break, embryo growth and
      germination were investigated: temperature and moisture requirements; effects of
      karrikinolide, gibberellic acid and aerosol smoke; and phenology. KEY RESULTS:
      Following exposure to wet/dry cycles at low or high temperatures, embryo growth
      and germination occurred, albeit slowly in all species at low temperatures when
      moisture was unlimited, corresponding to winter in south-west Australia. Photo
      regime influenced germination only in H. racemosa. Aerosol smoke triggered
      substantial germination during the 1st germination season in H. huegelii and H.
      hypericoides. CONCLUSIONS: Although the study species are con-generic, sympatric
      and produce seeds of identical morphology, they possessed different dormancy
      break and germination requirements. The physiological component of MPD was non
      deep in H. racemosa but varied in the other three species where more deeply
      dormant seeds required >1 summer to overcome dormancy and, thus, germination was
      spread over time. Embryos grew during winter, but future studies need to resolve
      the role of cold versus warm stratification by using constant temperature
      regimes. To include Mediterranean species with MPD, some modifications to the
      current seed-dormancy classification system may need consideration: (a) wet/dry
      conditions for warm stratification and (b) a relatively long period for warm
      stratification. These outcomes have important implications for improving
      experimental approaches to resolve the effective use of broadcast seed for
      ecological restoration.

PMID- 22362662
TI  - Advanced phenotyping offers opportunities for improved breeding of forage and
      turf species.
AB  - BACKGROUND AND AIMS: Advanced phenotyping, i.e. the application of automated,
      high-throughput methods to characterize plant architecture and performance, has
      the potential to accelerate breeding progress but is far from being routinely
      used in current breeding approaches. In forage and turf improvement programmes,
      in particular, where breeding populations and cultivars are characterized by high
      genetic diversity and substantial genotype * environment interactions, precise
      and efficient phenotyping is essential to meet future challenges imposed by
      climate change, growing demand and declining resources. SCOPE: This review
      highlights recent achievements in the establishment of phenotyping tools and
      platforms. Some of these tools have originally been established in remote
      sensing, some in precision agriculture, while others are laboratory-based imaging
      procedures. They quantify plant colour, spectral reflection, chlorophyll
      fluorescence, temperature and other properties, from which traits such as
      biomass, architecture, photosynthetic efficiency, stomatal aperture or stress
      resistance can be derived. Applications of these methods in the context of forage
      and turf breeding are discussed. CONCLUSIONS: Progress in cutting-edge molecular
      breeding tools is beginning to be matched by progress in automated non
      destructive imaging methods. Joint application of precise phenotyping machinery
      and molecular tools in optimized breeding schemes will improve forage and turf
      breeding in the near future and will thereby contribute to amended performance of
      managed grassland agroecosystems.

PMID- 22362663
TI  - Inoculation with arbuscular mycorrhizal fungi suppresses initiation of haustoria
      in the root hemiparasite Pedicularis tricolor.
AB  - BACKGROUND AND AIMS: Plant parasitism and arbuscular mycorrhizal (AM)
      associations have many parallels and share a number of regulatory pathways.
      Despite a rapid increase in investigations addressing the roles of AM fungi in
      regulating interactions between parasitic plants and their hosts, few studies
      have tested the effect of AM fungi on the initiation and differentiation of
      haustoria, the parasite-specific structures exclusively responsible for host
      attachment and nutrient transfer. In this study, we tested the influence of AM
      fungi on haustorium formation in a root hemiparasitic plant. METHODS: Using a
      facultative root hemiparasitic species (Pedicularis tricolor) with the potential
      to form AM associations, the effects of inoculation were tested with two AM
      fungal species, Glomus mosseae and Glomus intraradices, on haustorium initiation
      in P. tricolor grown alone or with Hordeum vulgare 'Fleet' (barley) as the host
      plant. This study consisted of two greenhouse pot experiments. KEY RESULTS: Both
      AM fungal species dramatically suppressed intraspecific haustorium initiation in
      P. tricolor at a very low colonization level. The suppression over-rode inductive
      effects of the parasite's host plant on haustoria production and caused
      significant growth depression of P. tricolor. CONCLUSIONS: AM fungi had strong
      and direct suppressive effects on haustorium formation in the root hemiparasite.
      The significant role of AM fungi in haustorium initiation of parasitic plants was
      demonstrated for the first time. This study provides new clues for the regulation
      of haustorium formation and a route to development of new biocontrol strategies
      in management of parasitic weeds.

PMID- 22362664
TI  - Natural foliar variegation without costs? The case of Begonia.
AB  - BACKGROUND AND AIMS: Foliar variegation is recognized as arising from two major
      mechanisms: leaf structure and pigment-related variegation. Begonia has species
      with a variety of natural foliar variegation patterns, providing diverse examples
      of this phenomenon. The aims of this work are to elucidate the mechanisms
      underlying different foliar variegation patterns in Begonia and to determine
      their physiological consequences. METHODS: Six species and one cultivar of
      Begonia were investigated. Light and electron microscopy revealed the leaf
      structure and ultrastructure of chloroplasts in green and light areas of
      variegated leaves. Maximum quantum yields of photosystem II were measured by
      chlorophyll fluorescence. Comparison with a cultivar of Ficus revealed key
      features distinguishing variegation mechanisms. KEY RESULTS: Intercellular space
      above the chlorenchyma is the mechanism of variegation in these Begonia. This
      intercellular space can be located (a) below the adaxial epidermis or (b) below
      the adaxial water storage tissue (the first report for any taxa), creating light
      areas on a leaf. In addition, chlorenchyma cell shape and chloroplast
      distribution within chlorenchyma cells differ between light and green areas.
      Chloroplasts from both areas showed dense stacking of grana and stroma thylakoid
      membranes. The maximum quantum yield did not differ significantly between these
      areas, suggesting minimal loss of function with variegation. However, the absence
      of chloroplasts in light areas of leaves in the Ficus cultivar led to an
      extremely low quantum yield. CONCLUSIONS: Variegation in these Begonia is
      structural, where light areas are created by internal reflection between air
      spaces and cells in a leaf. Two forms of air space structural variegation occur,
      distinguished by the location of the air spaces. Both forms may have a common
      origin in development where dermal tissue becomes loosely connected to mesophyll.
      Photosynthetic functioning is retained in light areas, and these areas do not
      include primary veins, potentially limiting the costs of variegation.

PMID- 22362665
TI  - Distribution of calcium (Ca) and magnesium (Mg) in the leaves of Brassica rapa
      under varying exogenous Ca and Mg supply.
AB  - BACKGROUND AND AIMS: Leafy vegetable Brassica crops are an important source of
      dietary calcium (Ca) and magnesium (Mg) and represent potential targets for
      increasing leaf Ca and Mg concentrations through agronomy or breeding. Although
      the internal distribution of Ca and Mg within leaves affects the accumulation of
      these elements, such data are not available for Brassica. The aim of this study
      was to characterize the internal distribution of Ca and Mg in the leaves of a
      vegetable Brassica and to determine the effects of altered exogenous Ca and Mg
      supply on this distribution. METHODS: Brassica rapa ssp. trilocularis 'R-o-18'
      was grown at four different Ca:Mg treatments for 21 d in a controlled
      environment. Concentrations of Ca and Mg were determined in fully expanded leaves
      using inductively coupled plasma-mass spectrometry (ICP-MS). Internal
      distributions of Ca and Mg were determined in transverse leaf sections at the
      base and apex of leaves using energy-dispersive X-ray spectroscopy (EDS) with
      cryo-scanning electron microscopy (cryo-SEM). KEY RESULTS: Leaf Ca and Mg
      concentrations were greatest in palisade and spongy mesophyll cells,
      respectively, although this was dependent on exogenous supply. Calcium
      accumulation in palisade mesophyll cells was enhanced slightly under high Mg
      supply; in contrast, Mg accumulation in spongy mesophyll cells was not affected
      by Ca supply. CONCLUSIONS: The results are consistent with Arabidopsis thaliana
      and other Brassicaceae, providing phenotypic evidence that conserved mechanisms
      regulate leaf Ca and Mg distribution at a cellular scale. The future study of
      Arabidopsis gene orthologues in mutants of this reference B. rapa genotype will
      improve our understanding of Ca and Mg homeostasis in plants and may provide a
      model-to-crop translation pathway for targeted breeding.

PMID- 22362666
TI  - Quantifying the impact of soil compaction on root system architecture in tomato
      (Solanum lycopersicum) by X-ray micro-computed tomography.
AB  - BACKGROUND AND AIMS: We sought to explore the interactions between roots and soil
      without disturbance and in four dimensions (i.e. 3-D plus time) using X-ray micro
      computed tomography. METHODS: The roots of tomato Solanum lycopersicum 'Ailsa
      Craig' plants were visualized in undisturbed soil columns for 10 consecutive days
      to measure the effect of soil compaction on selected root traits including
      elongation rate. Treatments included bulk density (1.2 vs. 1.6 g cm(-3)) and soil
      type (loamy sand vs. clay loam). KEY RESULTS: Plants grown at the higher soil
      bulk density exploited smaller soil volumes (P < 0.05) and exhibited reductions
      in root surface area (P < 0.001), total root volume (P < 0.001) and total root
      length (P < 0.05), but had a greater mean root diameter (P < 0.05) than at low
      soil bulk density. Swelling of the root tip area was observed in compacted soil
      (P < 0.05) and the tortuosity of the root path was also greater (P < 0.01). Root
      elongation rates varied greatly during the 10-d observation period (P < 0.001),
      increasing to a maximum at day 2 before decreasing to a minimum at day 4. The
      emergence of lateral roots occurred later in plants grown in compacted soil (P <
      0.01). Novel rooting characteristics (convex hull volume, centroid and maximum
      width), measured by image analysis, were successfully employed to discriminate
      treatment effects. The root systems of plants grown in compacted soil had smaller
      convex hull volumes (P < 0.05), a higher centre of mass (P < 0.05) and a smaller
      maximum width than roots grown in uncompacted soil. CONCLUSIONS: Soil compaction
      adversely affects root system architecture, influencing resource capture by
      limiting the volume of soil explored. Lateral roots formed later in plants grown
      in compacted soil and total root length and surface area were reduced. Root
      diameter was increased and swelling of the root tip occurred in compacted soil.

PMID- 22362668
TI  - Induced heterodimerization and purification of two target proteins by a synthetic
      coiled-coil tag.
AB  - A synthetic de novo designed heterodimeric coiled-coil was used to copurify two
      target fluorescent proteins, Venus and enhanced cyan fluorescent protein (ECFP).
      The coiled-coil consists of two 21-amino acid repetitive sequences, (EIAALEK)(3)
      and (KIAALKE)(3), named E3 and K3, respectively. These sequences were fused to
      the C-termini of ECFP or Venus followed by either a strep- or a his-tag,
      respectively, for affinity purification. Mixed lysates of Venus-K3 and ECFP-E3
      were subjected to consecutive affinity purification and showed highly specific
      association between the coiled-coil pair by SDS-PAGE, gel filtration, isothermal
      titration calorimetry (ITC), and fluorescence resonance energy transfer (FRET).
      The tagged proteins eluted as heterodimers at the concentrations tested. FRET
      analysis further showed that the coiled-coil pair was stable in buffers commonly
      used for protein purification, including those containing high salt concentration
      and detergent. This study shows that the E3/K3 pair is very well suited for the
      copurification of two target proteins expressed in vivo because of its high
      specificity: it forms exclusively heterodimers in solution, it does not interact
      with any cellular proteins and it is stable under different buffer conditions.

PMID- 22362669
TI  - Apoptotic neurodegeneration and spatial memory are not affected by sedative and
      anaesthetics doses of ketamine/medetomidine combinations in adult mice.
AB  - BACKGROUND: Ketamine is increasingly popular in clinical practice and its
      combination with alpha(2)-agonists can provide good anaesthetic stability. Little
      is known about the effects of this combination in the brain. Therefore, we
      investigated the effects of different concentrations of ketamine combined with
      medetomidine on cognition and its potential apoptotic neurodegenerative effect in
      adult mice. METHODS: Seventy-eight C57BL/6 adult mice were divided into six
      different groups (saline solution, 1 mg kg(-1) medetomidine, 25 mg kg(-1)
      ketamine+1 mg kg(-1) medetomidine, 75 mg kg(-1) ketamine+1 mg kg(-1)
      medetomidine, 25 mg kg(-1) ketamine, and 75 mg kg(-1) ketamine). Eight animals
      per group were tested in the T-maze, vertical pole, and open-field test. Five
      animals per group were used for histopathological [haematoxylin and eosin (HE)
      staining] and immunohistochemical analyses [caspase-3 activation and expression
      of neurotrophin brain-derived neurotrophic factor (BDNF)]. Cells showing clear HE
      staining and positive immunoreactions for caspase-3 and BDNF in the retrosplenial
      cortex, visual cortex, pyramidal cell layer of the cornu Ammonis 1 and cornu
      Ammonis 3 areas of the hippocampus, and in the granular layer of the dentate
      gyrus were counted. RESULTS: There were no differences between groups regarding
      the number of dead cells and cells showing positive immunoreactions in the
      different areas of the brain studied. Similarly, no differences were detected in
      the number of trials to complete the T-maze task. Nevertheless, alpha(2)-agonist
      decreased hyperlocomotion caused by ketamine in the open field. CONCLUSIONS:
      Neither apoptotic neurodegeneration nor alterations in spatial memory were
      observed with different concentrations of ketamine combined with medetomidine in
      adult mice.

PMID- 22362670
TI  - Aprotinin, transfusions, and kidney injury in neonates and infants undergoing
      cardiac surgery.
AB  - BACKGROUND: A significantly increased risk of acute kidney injury (AKI) with the
      prophylactic use of aprotinin has been reported in adults undergoing cardiac
      surgery, but not in children. Blood product transfusions have also been shown to
      carry an independent risk of AKI. The present study assessed associations between
      AKI, aprotinin, and transfusions in neonates and infants undergoing cardiac
      surgery. METHODS: All neonates and infants undergoing surgery with
      cardiopulmonary bypass over a 42 month period, before and after the withdrawal of
      aprotinin, were included retrospectively. AKI was assessed by the Acute-Kidney
      Injury-Network classifications. A propensity score was used to balance treated
      and untreated groups. RESULTS: Three hundred and ninety patients received
      aprotinin and 568 patients did not. Inverse probability of treatment weighting
      resulted in good balance between groups for baseline and surgical
      characteristics. Controls underwent surgery with smaller bypass circuits and
      fewer transfusions. After adjustment for the use of miniaturized circuits and for
      the year of surgery, no significant association between the incidence of AKI,
      dialysis, and aprotinin was noted. Red blood cell transfusions were associated
      with an increased risk of AKI and dialysis: odds ratios (ORs) 1.64 (1.12-2.41)
      and 2.07 (1.13-3.73), respectively; as were fresh frozen plasma transfusions, ORs
      2.28 (1.68-3.09) and 3.11 (1.95-4.97), respectively. Platelet transfusions were
      associated with an increased risk of dialysis: OR 2.20 (1.21-4.01). CONCLUSIONS:
      Blood product transfusions, but not the prophylactic use of aprotinin, are
      significantly associated with AKI after cardiac surgery in neonates and infants.

PMID- 22362671
TI  - Association of sustained cardiovascular recovery with epinephrine in the delayed
      lipid-based resuscitation from cardiac arrest induced by bupivacaine overdose in
      rats.
AB  - BACKGROUND: The role of epinephrine combined with lipid emulsion in rescuing
      cardiovascular collapse induced by local anaesthetic overdose remains unclear.
      The objective of this study was to explore the effect of epinephrine on delayed
      lipid-based treatment for bupivacaine-induced cardiac arrest in rats. METHODS:
      Thirty-two rats were subjected to bupivacaine to induce asystole. Basic life
      support was performed for 10 min before the rats received saline, epinephrine
      alone, or 20% lipid emulsion bolus with or without epinephrine pretreatment. ECG
      and invasive arterial pressure were monitored continuously. Arterial blood gas
      was analysed at 25 min; the right lungs and hearts of rats were harvested for
      measurement of dry-to-wet lung weight ratio and myocardial bupivacaine content,
      respectively. RESULTS: In the rats treated with epinephrine plus lipid emulsion,
      there was a marked improvement in haemodynamic parameters at 25 min compared with
      rats treated with lipid alone, P<0.05. The coronary perfusion pressure
      immediately after lipid rescue was higher in the epinephrine/lipid-treated rats
      when compared with rats given lipid only (70 and 24 mm Hg, respectively, P<0.05).
      The myocardial bupivacaine content was lower (8.34 nM g(-1)) in the
      epinephrine/lipid group relative to other groups (P<0.05). However, the rats
      treated with lipid alone which survived had higher PO(2), less severe acidosis,
      and better hypoxaemia relative to surviving rats given epinephrine plus lipid.
      CONCLUSIONS: Late intervention with epinephrine plus lipid emulsion contributed
      to sustained improvement in haemodynamic profile, but failed to alleviate
      deterioration of hypoxaemia and acidaemia in rats.

PMID- 22362672
TI  - Preoperative pregabalin administration significantly reduces postoperative opioid
      consumption and mechanical hyperalgesia after transperitoneal nephrectomy.
AB  - BACKGROUND: Preoperative administration of pregabalin is proposed as a promising
      way of enhancing postoperative pain control. Whereas a few studies have
      investigated the effect of pregabalin on postoperative opioid consumption, no
      study has focused on the influence on postoperative hyperalgesia. In this
      randomized, triple-blinded, placebo-controlled study, we aimed to demonstrate
      that a single, preoperative dose of pregabalin reduces postoperative opioid
      consumption, mechanical hyperalgesia, and pain sensitivity. METHODS: Patients
      undergoing elective transperitoneal nephrectomy received 300 mg pregabalin or
      placebo 1 h before anaesthesia. After operation, patients received piritramide
      via a patient-controlled analgesia device. Pain levels and side-effects were
      documented. The area of hyperalgesia for punctuate mechanical stimuli around the
      incision was measured 48 h after the operation with a hand-held von Frey
      filament. Mechanical pain threshold was tested before and 48 h after surgery with
      von Frey filaments with increasing diameters. RESULTS: In each group, 13 patients
      were recruited. Total piritramide consumption [77 (16) vs 52 (16) mg, P=0.0004]
      and the normalized area of hyperalgesia [143 (87) vs 84 (54) cm(2), P=0.0497]
      were significantly decreased in the pregabalin group. There were no significant
      differences in mechanical pain threshold levels [1.20 (0.56) log(g) vs 1.05
      (0.58) log(g), P=0.6738]. No case of severe sedation was reported in both groups.
      No other side-effects were observed. CONCLUSIONS: Our study has shown that
      preoperative administration of 300 mg pregabalin in patients undergoing
      transperitoneal nephrectomy reduces postoperative opioid consumption and
      decreases the area of mechanical hyperalgesia.

PMID- 22362673
TI  - Central venous thrombosis and perioperative vascular access in adult intestinal
      transplantation.
AB  - BACKGROUND: Venous access is crucial in intestinal transplantation, but a
      thrombosed venous system may prevent the use of central veins of the upper body.
      The incidence of venous thrombosis and the necessity to perform alternative
      vascular access (AVA) in intestinal transplant recipients have not been fully
      investigated. METHODS: Records of adult patients who underwent intestinal
      transplantation between January 1, 2001, and December 31, 2009, were reviewed.
      Contrast venography was performed as pre-transplantation screening. Vascular
      accesses at the transplantation were categorized as I (percutaneous line via the
      upper body veins), II (percutaneous line via the lower body veins), and III
      (vascular accesses secured surgically, with interventional radiology, or using
      non-venous sites). Categories II and III were defined as AVA. Risk factors for
      central venous thrombosis and those for requiring AVA were analysed,
      respectively. RESULTS: Among 173 patients, central venous obstruction or stenosis
      (<50% of normal diameter) was found in 82% (141 patients). AVA was required in
      4.6% (eight patients: four in each category II and III). Large-bore infusion
      lines were placed via the femoral arteries in all category III patients without
      complications. Existing inferior vena cava filter and hypercoagulable states were
      identified as the risk factors for the use of AVA, but not for central venous
      thrombosis. Outcomes of patients who underwent AVA were similar to those of
      patients without AVA. CONCLUSIONS: The majority of adult patients undergoing
      intestinal transplantation had at least one central venous stenosis or
      obstruction. The recipient outcomes were comparable when either standard vascular
      access or AVA was used for transplantation.

PMID- 22362674
TI  - Modification of a draw-over vaporizer for use with sevoflurane.
AB  - BACKGROUND: Draw-over anaesthesia is widely used throughout the developing world,
      in disaster areas and in military anaesthesia when the supply of pressurized
      oxygen is unreliable. To date, no draw-over vaporizer has been able to deliver
      sufficient concentrations of sevoflurane for use in inhalation induction of
      anaesthesia. A laboratory study to assess the performance of a new vaporizer
      (DDV2) to deliver sevoflurane in a wide range of situations is described.
      METHODS: In this study, the concentration of sevoflurane delivered at different
      dial settings (1-4%) and at different temperatures (20-40 degrees C) in a draw
      over mode was measured. The concentration of sevoflurane delivered at different
      dial settings with continuous flow (6 and 8 litre min(-1)) at 20 degrees C was
      measured. The maximum possible concentration of sevoflurane that can be delivered
      by the DDV2 was measured at a continuous flow rate of 8 litre min(-1) at 20, 30,
      and 40 degrees C. RESULTS: Concentrations of sevoflurane delivered in the draw
      over mode were within 0.5% of dialled setting up to 30 degrees C. Above this
      temperature, higher levels of vapour were delivered. With continuous flow,
      concentrations of sevoflurane at 20 degrees C were within 0.5% of dialled setting
      and were stable throughout the duration of the experiment. On the 'induction'
      setting, concentrations of sevoflurane of between 6.4% and 10.1% could be
      delivered with continuous flow. CONCLUSIONS: The modifications to the DDV2 allow
      stable concentrations of sevoflurane to be delivered in draw-over and continuous
      flow modes over a range of temperatures. With continuous flow, concentrations of
      sevoflurane sufficient for induction of anaesthesia can be achieved.

PMID- 22362675
TI  - Increased osteoblast adhesion on physically optimized KRSR modified calcium
      aluminate.
AB  - Calcium aluminate (CA) is a porous biocompatible material easily cast at room
      temperature. Through this casting process, the average surface pore size of CA
      was varied from an average of 100 to 290 microns. The optimal surface pore size
      of the hydrated CA for cell viability was determined to be 100 microns. Further,
      a three step-solution deposition technique was developed to covalently immobilize
      cell adhesion peptides, RGD, and KRSR to the CA surface. Cell adhesion for 1-, 4
      , and 7-day time periods was tested with primary osteoblasts and NIH 3T3
      fibroblasts. Both peptides were found to increase fibroblast adhesion to the CA
      surface. However, only KRSR increased osteoblast adhesion to the surface of the
      CA, which may aid in bone formation after implantation.

PMID- 22362676
TI  - Multi-use NBD-based tetra-amino macrocycle: fluorescent probe for metals and
      anions and live cell marker.
AB  - Ligand L (4-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-1,7-dimethyl-1,4,7,10-tetra
      azacyclododecane) is a versatile fluorescent sensor useful for Cu(II), Zn(II) and
      Cd(II) metal detection, as a building block of fluorescent metallo-receptor for
      halide detection, and as an organelle marker inside live cells. Ligand L
      undergoes a chelation-enhanced fluorescence (CHEF) effect upon metal coordination
      in acetonitrile solution. In all three complexes investigated the metal cation is
      coordinatively unsaturated; thus, it can bind secondary ligands as anionic
      species. The crystal structure of [ZnLCl](ClO(4)) is discussed. Cu(II) and Zn(II)
      complexes are quenched upon halide interaction, whereas the [CdL](2+) species
      behaves as an OFF-ON sensor for halide anions in acetonitrile solution. The
      mechanism of the fluorescence response in the presence of the anion depends on
      the nature of the metal ion employed and has been studied by spectroscopic
      methods, such as NMR spectroscopy, UV/Vis and fluorescence techniques and by
      computational methods. Subcellular localization experiments performed on HeLa
      cells show that L mainly localizes in spot-like structures in a polarized portion
      of the cytosol that is occupied by the Golgi apparatus to give a green
      fluorescence signal.

PMID- 22362677
TI  - Optimal surgical planning guidance for lumbar spinal fusion considering
      operational safety and vertebra-screw interface strength.
AB  - BACKGROUND: An optimized pre-operative planning framework for lumbar spinal
      fusion was proposed, which augmented a novel functionality of suggesting optimal
      insertion trajectories and the screw size, considering operational safety and
      vertebra-screw interface strength, autonomously. METHODS: Based on an accurate 3D
      pedicle model with pre-operative computed tomography (CT) data, the framework
      begins with safety margin estimation for each potential insertion trajectory,
      followed by procedures to collect a set of insertion trajectories satisfying the
      operation safety objective. Among the trajectory candidates, the insertion
      trajectory, which maximized the insertable depth of a pedicle screw into the
      vertebral body, was then chosen as optimal, because the insertable depth enhanced
      the strength of the screw-vertebra interface. The radius of a pedicle screw was
      chosen as 70% of the pedicle radius. RESULTS: This framework has been tested on
      176 spinal pedicles of 20 patients requiring spinal fusion. It was successfully
      applied, resulting in an average success rate of 100% and a final safety margin
      of 2.1 +/- 0.2 mm. Planning accuracy and usefulness of the proposed surgical
      planner show significant differences compared with a conventional manual planner.
      CONCLUSION: We can expect that the derived conservative safety margin mitigates
      screw misplacement or pedicle breach, despite potential errors induced during
      registrations or intraoperative screw insertion.

PMID- 22362678
TI  - The diagnostic efficacy of combining bronchoscopic tissue biopsy and
      endobronchial ultrasound-guided transbronchial needle aspiration for the
      diagnosis of malignant lesions in the lung.
AB  - Bronchoscopic tissue forceps biopsy (BBX) is a standard procedure for diagnosis
      of malignancy in the lung. Endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) has proven to be a sensitive alternative to tissue biopsy
      for the diagnosis and staging of lung tumors. We report our institutional
      experience with diagnostic yield when combining BBX and EBUS-TBNA in the
      bronchoscopic evaluation of patients presenting with lung lesion(s). The
      pathology files at our institution were searched for all patients who underwent
      combined BBX and EBUS-TBNA procedures between 1/09 and 6/10 for the diagnosis of
      malignancy. The data points included biopsy site, cytologic, and histopathologic
      diagnoses and follow-up. We identified 115 patients who underwent BBX combined
      with EBUS-TBNA. About 107 (93%) of the patients received a definitive pathologic
      diagnosis; 93 (81%) were malignant. BBX and EBUS-TBNA of the lung lesion only
      were performed in 21 patients, BBX and EBUS-TBNA of lymph node(s) only in 78
      patients with BBX and a combination of EBUS-TBNA of the lung lesion and lymph
      node(s) in 16 patients. Immunostains were performed for 71 (76%) patients and
      molecular testing for 11 (12%) patients. Diagnostic yield is increased when
      bronchoscopic technologies are combined. In a significant number of patients
      where BBX was negative, EBUS-TBNA provided diagnostic material, increasing
      diagnostic yield by 18%. In a subset of these patients the EBUS-TBNA assisted in
      the staging of a primary tumor. By combining these procedures, more tissue was
      obtained for immunohistochemistry and molecular testing, which facilitated
      personalized management in a minimally invasive manner.

PMID- 22362679
TI  - The British HIV Association/British Association for Sexual Health and HIV
      Position Statement on pre-exposure prophylaxis in the UK.

PMID- 22362680
TI  - High prevalence of Mycoplasma genitalium among female sex workers in Honduras:
      implications for the spread of HIV and other sexually transmitted infections.
AB  - This study describes HIV, sexually transmitted infections (STI) and risk factors
      associated with Mycoplasma genitalium among female sex workers (FSWs) in four
      cities in Honduras. In 2006, 795 FSWs from Tegucigalpa, San Pedro Sula, La Ceiba
      and Comayagua were recruited using respondent-driven sampling (RDS) and tested
      for HIV prevalence and STI. HIV prevalence ranged from no infections in Comayagua
      to 5.4% in Tegucigalpa. With the exception of Comayagua, more than 20% of FSWs
      were infected with M. genitalium. M. genitalium in the aggregated cities was
      associated with HIV positivity, being aged <=30 years old, drinking alcohol more
      than once weekly and always using condoms with regular clients in the past month.
      In comparison with a 2001 surveillance study we found lower rates of HIV
      infection. Interventions for HIV control and prevention among FSWs, including
      promotion of condom use, are needed in Honduras.

PMID- 22362681
TI  - Cervical cytological abnormalities and factors associated with high-grade
      squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro,
      Brazil.
AB  - Although cervical cancer remains a major public health problem in Brazil,
      knowledge of cervical cytological abnormalities among HIV-infected women remains
      scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil,
      703 HIV-infected women underwent cytology-based cervical cancer screening and
      human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to
      evaluate the association of factors with the presence of high-grade squamous
      intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the
      women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with
      the presence of HSIL was age (>=25 and <=40 years, prevalence ratio [PR] 2.60,
      95% confidence interval [CI] 1.11-6.10), and more than three pregnancies was
      protective (PR 0.33, 95% CI 0.11-0.94). High coverage of cervical cancer
      screening is warranted to prevent morbidity and mortality from cervical cancer in
      this population.

PMID- 22362682
TI  - Difficulties experienced in defining the microbial cause of pelvic inflammatory
      disease.
AB  - Clinical assessment of women with pelvic pain was a poor indicator of disease
      seen at laparoscopy. Thus, of 109 women, 22 at laparoscopy had salpingitis, 19
      had adhesions without salpingitis, 20 had endometriosis or ovarian pathology and
      48 no observable abnormality. In all laparoscopic categories, Ureaplasma spp. and
      Mycoplasma hominis, but not Mycoplasma genitalium, were at least as common in the
      cervix/vagina as Chlamydia trachomatis and equally frequent in the endometrium.
      However, C. trachomatis had the greatest propensity for spread to the Fallopian
      tubes. Thus, of 28 women who had C. trachomatis organisms in the vagina/cervix,
      13 had them in a Fallopian tube (ratio 2.2:1); the ratio was 6:1 for Neisseria
      gonorrhoeae, 8:1 for M. genitalium, 21:1 for M. hominis and 31:1 for Ureaplasma
      spp. M. hominis organisms in a large number were detected most often in women
      with salpingitis. The likelihood of spread of Ureaplasma urealyticum and U.
      parvum from the lower to the upper genital tract was about the same and they were
      detected only once each in a tube, which was not inflamed in either case.
      Multiple bacteria were often detected at a single site, making it difficult to
      establish the exact cause of disease. However N. gonorrhoeae was considered to be
      the sole cause of salpingitis in one woman and the primary or equal primary
      contributor in four others; C. trachomatis was involved in at least 11 women,
      mostly as the sole cause or as the primary contributor; M. genitalium was
      considered the cause in one woman and had possible involvement in three others;
      and M. hominis was a questionable sole cause in one woman and the primary or
      equal primary contributor in three. Serologically, C. trachomatis was related to
      adhesions, without salpingitis, more often (63%) than any other micro-organism.
      M. genitalium may have been implicated in one case. Serologically, a previous C.
      trachomatis infection was indicated in 40% of women without an observable
      laparoscopic abnormality. C. trachomatis in the endometrium and tubes of women
      without any laparoscopic abnormality suggests subclinical disease, endometritis
      or endosalpingitis. There was evidence for a smaller proportion (19%) of women
      without an abnormality having been infected previously with M. genitalium. To
      some extent this is consistent with the infrequency of acute M. genitalium
      infections in this cohort of women.

PMID- 22362683
TI  - Sports behaviour among HIV-infected versus non-infected individuals in a Berlin
      cohort.
AB  - Physical activity has been recommended based on beneficial effects described in
      HIV-infected patients. However, such guidelines do not take into account actual
      sport behaviours and general attitudes towards physical activity. To evaluate
      actual sport activity and attitudes towards sport in HIV-infected versus non
      infected individuals we conducted an anonymous questionnaire investigating the
      prevalence, as well as possible changes, in sports engagement and the overall
      attitude to physical activity. A total of 283 patients of a general care facility
      specialized in the treatment of HIV/AIDS in Berlin, Germany, participated; 124
      were HIV infected and 159 were non-infected, mostly men who have sex with men
      (MSM) (88%), with a median age of 35 years. The HIV-infected participants had a
      median CD4+ count of 554 cells/uL and 48.8% of them were using antiretroviral
      therapy (ART) at the time of survey. The proportion of patients actually
      performing physical activity was significantly lower (P = 0.028) within the HIV
      infected group (61.3%) than within the non-infected group (74.2%). This
      difference remained significant after accounting for possible confounders such as
      age, gender, injecting drug use and sexual preferences. Previously reported sport
      activity prevalence was similar in both groups on leaving school. From our data
      we could not identify an association between the time of HIV diagnosis and
      changes in sports activity. In conclusion, fewer HIV-infected individuals report
      physical activity than non-infected individuals. Sociodemographic studies to
      evaluate potential differences in sports behaviour are required in order to
      inform exercise guidelines for HIV-infected patients.

PMID- 22362684
TI  - Acceptance of self-testing for increased vaginal pH in different subsets of
      Ugandan women.
AB  - We assessed the acceptance of self-testing for vaginal pH in 344 Ugandan women in
      different clinical settings. Women tested themselves by insertion of a gloved
      finger into the vagina to test vaginal pH and provide a smear on a glass slide.
      None of the tested women found the test very difficult: 8% found it somewhat
      difficult, 16% rather easy and 76% very easy to do. Of the 20% who found it
      difficult to read the test result, more women were attending a family planning
      clinic or had a higher diploma (P = 0.001). Pregnant women were least likely to
      understand of the meaning of the test, while those visiting family planning
      clinics had the opposite experience. HIV-infected women were most motivated to
      accept: 95% would be happy to use the test more often if requested, and another
      3.5% felt they might be better motivated to do repeat testing after extra
      explanation. Self-sampling of vaginal pH is well accepted by Ugandan women. Our
      new method also allows diagnostic work-up by formal microscopy. Before commencing
      large-scale population screening, unexpected reactions of different
      subpopulations should be taken into account.

PMID- 22362685
TI  - Rates and determinants of HIV-attributable mortality among rural female sex
      workers in Northern Karnataka, India.
AB  - Female sex workers (FSWs) have among the highest rates of HIV infection in India.
      However, little is known about their HIV-specific mortality rates. In total, 1561
      FSWs participated in a cohort study in Karnataka. Outcome data (mortality) were
      available on 1559 women after 15 months of follow-up. To gather details on
      deaths, verbal autopsy (VA) questionnaires were administered to key informants.
      Two physicians reviewed the VA reports and assigned underlying causes of death.
      Forty-seven deaths were reported during the follow-up (overall mortality rate was
      2.44 per 100 person-years), with VA data available on 45 women. Thirty-five
      (75.6%) of these women were known to be HIV-positive, but only 42.5% were on
      antiretroviral therapy (ART). Forty deaths were assessed to be HIV-related, for
      an HIV-attributable mortality rate of 2.11 deaths per 100 person-years. Absence
      of a current regular partner (incidence rate ratio: 2.79; 95% confidence interval
      [CI]: 1.39-5.60) and older age (1.06; 1.01-1.11) were associated with increased
      HIV-attributable mortality. Reported duration in sex work was not related to HIV
      attributable mortality. We found a high HIV-related mortality rate among this
      cohort of FSWs; nearly 10 times that of national mortality rates among women of a
      similar age group. Older age, but not reported duration in sex work, was
      associated with increased mortality, and suggests HIV acquisition prior to self
      reported initiation into sex work. Despite significant efforts, there remain
      considerable gaps in HIV prevention near or before entry into sex work, as well
      as access and uptake of HIV treatment among FSWs.

PMID- 22362686
TI  - Knowledge of human papillomavirus and anal cancer among men who have sex with men
      attending a New York City sexually transmitted diseases clinic.
AB  - Men who have sex with men (MSM) are at risk for human papillomavirus (HPV)
      infection and anal cancer (AC) yet little is known regarding MSM knowledge and
      risk perception for these outcomes. We surveyed 116 MSM attending a sexually
      transmitted disease clinic and found that over a quarter (27%) did not know HPV
      is transmitted via anal sex and most (77%) were unaware of the link with AC. Many
      MSM (60%) perceived risk for HPV; far fewer (35%) perceived risk for AC. In
      adjusted logistic regression analyses, having friends or acquaintances with HPV
      or genital warts was associated with knowledge of anal HPV transmission (odds
      ratio [OR] = 4.3; 95% confidence interval [CI] = 1.4, 13.4) and AC risk
      perception (OR = 6.2; 95% CI = 2.3, 16.7); reporting a regular source of care was
      associated with awareness of a link between HPV and AC (OR = 3.1; 95% CI = 1.1,
      9.1); and MSM and women versus MSM, had less perceived risk for HPV (OR = 0.05;
      CI = 0.01, 0.29). Nearly all expressed hypothetical acceptance of HPV vaccine. In
      our sample, many MSM were unaware of a link between MSM sexual practices and HPV
      related outcomes.

PMID- 22362687
TI  - Factors associated with viral load suppression in HIV-infected pregnant women in
      Rio de Janeiro, Brazil.
AB  - Viral load (VL) near delivery is a determinant of mother-to-child transmission
      (MTCT) of HIV. To evaluate factors associated with an undetectable VL near
      delivery in HIV-infected pregnant women receiving highly active antiretroviral
      therapy (HAART) and non-HAART regimens, HIV-infected pregnant women with a
      detectable VL at entry and having used antiretrovirals for >=4 weeks before
      delivery were selected. Multivariate analysis was employed using binary logistic
      unconditional models; the dependent variable was having a VL <400 copies/mL near
      delivery. VL suppression was achieved in 403/707 women (57%): 65.4% in the HAART
      group, but only 26% in the non-HAART group P = 0.001. Duration of HAART was
      correlated with VL suppression, with maximum benefit seen after >=12 weeks of
      therapy (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.72-3.65). CD4+
      cell count near delivery (OR: 1.53; 95% CI: 1.06-2.20) and baseline VL (OR: 0.74;
      95% CI: 0.58-0.94) were also independently associated with VL suppression.
      Overall MTCT rate was 1.6%. HAART for >=12 weeks, baseline VL and CD4 cell count
      near delivery were independently associated with viral suppression near delivery.

PMID- 22362688
TI  - Viral infections of the pubis.
AB  - There are no demographic data published on those with viral infections of the
      pubis (VIPs). We conducted a two-year prospective study to collect demographic
      information on patients with VIPs. Data were gathered on age, sex, diagnosis, low
      (<=10) or high (>10) lesion number, symptoms, how the patient discovered the
      lesions, localization, lesions beyond the pubis, risk factors, shaving habits,
      human papillomavirus (HPV) vaccination status and treatment. In a total of 61
      patients, molluscum contagiosum (MC) was identified in 71%, condylomata acuminata
      (CA) in 11%, concomitant MC and CA infections in 11% and herpes simplex virus
      (HSV) infection in 4.8%. Shaving represented a risk factor for a high lesion
      number, but not for the extension beyond the pubis. MC, CA and HSV infections
      affecting the pubis are uncommon and often asymptomatic. As they may represent a
      hidden source of infection we recommend thorough inspection of the pubis during
      routine skin examination.

PMID- 22362689
TI  - Genitourinary medicine clinic policies on domestic violence across England and
      Wales: a postal questionnaire survey.
AB  - Domestic violence (DV) is prevalent in the UK. There are no national
      recommendations for assessment of DV in genitourinary (GU) medicine clinics.
      Bournemouth GU medicine clinic has a referral pathway for victims of DV. A postal
      questionnaire survey was carried out to determine whether GU medicine clinics
      across England and Wales had local policies in place to assess DV and also to
      establish their views on routine assessment of DV within GU medicine. The
      response rate was 53%. Most clinics had access to patient literature. Only 20% of
      the clinics had a policy in place to assist victims of DV. Although over 50%
      agreed that routine assessment for DV should happen in GU medicine clinics, only
      11% clinics routinely asked about DV.

PMID- 22362690
TI  - A national audit on the management of pelvic inflammatory disease in UK
      genitourinary medicine clinics.
AB  - The prompt and effective treatment of pelvic inflammatory disease (PID) may
      reduce the risk of complications such as infertility, ectopic pregnancy and
      pelvic pain. We conducted a national audit to investigate the treatment of women
      diagnosed with PID and associated rates of partner notification in genitourinary
      (GU) medicine clinics during 2008 and compared our results with the British
      Association of Sexual Health and HIV (BASHH) 2005 national guideline. Among a
      total of 1,105,587 female attendees, national data showed 18,421 cases of PID
      diagnosed in GU medicine clinics, giving an incidence of 167 cases per 10,000
      attendences. We audited a national sample of 1132 PID cases for review. Of those,
      504 (44.5%) received a recommended treatment regimen and 447 (39%) of named male
      contacts were treated. Adherence to recommended treatment and partner
      notification did not reach national standards.

PMID- 22362691
TI  - Improvement is needed in the documentation and HIV testing of children of HIV
      positive women.
AB  - We assessed our unit's documentation of the HIV status of 146 identifiable
      existing children of 146 women audited, out of our total cohort of 329 HIV
      positive women. For 23 women (16%) there was no documentation of the presence or
      absence of children. For 81 children of 43 (29%) women the HIV status was
      unknown. Of these children, at least eight (5.5%) reside in the UK and could be
      accessed for testing. It is essential that documentation and testing of children
      of HIV-positive women takes place to prevent potentially fatal late-stage
      presentations of AIDS and onward transmission of HIV as young people become
      sexually active.

PMID- 22362692
TI  - Increasing cervical cytology uptake in Glasgow HIV cohort.
AB  - We present an audit of cervical smear uptake in our HIV-positive cohort in
      Glasgow. Uptake was favourable in comparison with the general population in the
      rest of Scotland (75% versus 73.4%); however, much lower than the British
      Association for Sexual Health and HIV (BASHH) recommended standard of 95%. A
      significant number of patients were incorrectly identified as only requiring
      three-yearly smears when they attended non-specialist services which may
      contribute to reduced uptake.

PMID- 22362693
TI  - Severe vitamin D deficiency in a patient treated for hepatitis B with tenofovir.
AB  - With the increasing use of tenofovir disoproxil in the management of HIV and
      hepatitis B, serious adverse effects, such as renal dysfunction, will inevitably
      increase in frequency. We describe a case of a patient presenting with
      hypophosphataemia suggestive of Fanconi's syndrome, but in fact explicable by
      simple vitamin D deficiency. This emphasizes that while monitoring for adverse
      effects is recommended, physicians must consider all alternative causes for
      biochemical abnormalities prior to discontinuing tenofovir and delaying
      appropriate management.

PMID- 22362694
TI  - Hyperhidrosis related to nevirapine therapy.
AB  - A 70-year-old white man presented to the internal medicine outpatient clinic with
      symptoms of significant hyperhidrosis. He had been started on antiretroviral
      therapy (ART) with tenofovir, lamivudine and nevirapine. The patient complained
      of excessive sweating following severe asthenia after taking nevirapine. Based on
      these findings, we suspected that the causative agent was nevirapine and a
      diagnosis of hyperhidrosis due to nevirapine was made. Nevirapine treatment was
      stopped and was substituted with efavirenz: the patient continued on therapy with
      tenofovir and lamivudine. The hyperhidrosis symptoms resolved in 2-3 days. No
      relapse was observed with the new ART regimen. Drugs that induce hyperhidrosis
      can cause patient discomfort and embarrassment. In our patient, this adverse drug
      reaction also caused severe asthenia that decreased the patient's physical and
      emotional quality of life. There was a temporal relationship between the
      developments of symptoms and starting nevirapine therapy. Once nevirapine was
      suspended and switched to efavirenz, excessive sweating resolved. An objective
      causality assessment revealed that the adverse effect was probable. Until further
      data are available, clinicians should consider discontinuation of nevirapine
      therapy in patients who develop severe hyperhidrosis.

PMID- 22362695
TI  - A rare skin presentation of Penicillium marneffei infection in an AIDS patient.
AB  - Penicillium marneffei is an opportunistic fungal pathogen in HIV disease. We
      report the case of a patient with AIDS who presented with general weakness and
      generalized skin rashes. No specific allergic history or recent medication were
      reported. The skin lesions disappeared after adequate antifungal therapy. A blood
      culture obtained from the patient confirmed the presence of P. marneffei,
      infection which is characterized by cutaneous umbilicated lesions in AIDS
      patients. We report this case on account of the unusual skin presentation.

PMID- 22362696
TI  - HIV-associated gastric natural killer/T-cell lymphoma.
AB  - Natural killer (NK)/T-cell lymphoma is a rare form of non-Hodgkin's lymphoma that
      is seen with increased frequency in HIV infection and in transplant recipients.
      This case report describes an unusual case of extranodal NK/T-cell lymphoma in a
      patient with advanced HIV disease in which gastric involvement was a significant
      feature.

PMID- 22362697
TI  - Immune reconstitution renal-limited sarcoidosis presenting as acute kidney
      injury.
AB  - An HIV-infected asymptomatic woman developed acute kidney injury six weeks after
      initiation of combination antiretroviral therapy (cART). A renal biopsy revealed
      both renal-limited sarcoidosis and HIV nephropathy. The acute renal injury
      reversed with glucocorticoid therapy.

PMID- 22362698
TI  - Co-trimoxazole-induced myopia in an HIV-positive patient.
AB  - Co-trimoxazole is a commonly used drug in the treatment and prophylaxis of
      opportunistic infections in HIV seropositive patients. We report a case of a 35
      year-old HIV-infected man who presented with blurring of vision one week
      following initiation of co-trimoxazole therapy. A diagnosis of co-trimoxazole
      induced myopia, a known idiosyncratic drug reaction, was made. The drug was
      withheld and the myopia resolved completely. Although in this patient the ocular
      condition resolved completely, serious ocular adverse reactions have also been
      reported with co-trimoxazole. This case report highlights the occurrence of
      ocular adverse drug reactions (ADRs) in HIV-infected patients on co-trimoxazole
      and the complexity of drug interactions.

PMID- 22362699
TI  - Lichen planus of the external urinary meatus masquerading sexually transmitted
      disease.
AB  - Lichen planus is a chronic inflammatory mucocutaneous disorder of the skin
      including the scalp, the nails, and the oral and genital mucosae. Ocular,
      oesophageal, bladder, nasal, laryngeal, otic, gastric, and anal involvement has
      been documented. In this report, we describe a unique case of orogenital lichen
      planus affecting the external urinary meatus, masquerading as sexually
      transmitted urethritis and erosive genital disease.

PMID- 22362700
TI  - Implanon failure in an HIV-positive woman on  antiretroviral therapy resulting in
      two ectopic pregnancies.

PMID- 22362701
TI  - Can emergency departments fulfil BASHH recommendations for 24-hour access to HIV
      postexposure prophylaxis following sexual exposure?

PMID- 22362703
TI  - The more gold--the more enantioselective: cyclohydroaminations of gamma-allenyl
      sulfonamides with mono-, bis-, and trisphospholane gold(I) catalysts.
AB  - A series of chiral mono-, di-, and trinuclear gold(I) complexes have been
      prepared and used as precatalysts in the asymmetric cyclohydroamination of N
      protected gamma-allenyl sulfonamides. The stereodirecting ligands were mono-, di
      , and tridentate 2,5-diphenylphospholanes, which possessed C(1), C(2), and C(3)
      symmetry, respectively, thereby rendering the catalytic sites in the di- and
      trinuclear complexes symmetry equivalent. The C(3)-symmetric trinuclear complex
      displayed the highest activity and enantioselectivity (up to 95 % ee), whilst its
      mono- and dinuclear counterparts exhibited considerably lower
      enantioselectivities and activities. A similar trend was observed in a series of
      mono-, di-, and trinuclear 2,5-dimethylphospholane gold(I) complexes. Aurophilic
      interactions were established from the solid-state structures of the trinuclear
      gold(I) complexes, thereby raising the question as to whether these secondary
      forces were responsible for the different catalytic behavior observed.

PMID- 22362702
TI  - In situ 19F NMR studies of an E. coli membrane protein.
AB  - In this report, (19)F spin incorporation in a specific site of a specific
      membrane protein in E. coli was accomplished via trifluoromethyl-phenylalanine
      ((19) F-tfmF). Site-specific (19)F chemical shifts and longitudinal relaxation
      times of diacylglycerol kinase (DAGK), an E. coli membrane protein, were measured
      in its native membrane using in situ magic angle spinning (MAS) solid state
      nuclear magnetic resonance (NMR). Comparing with solution NMR data of the
      purified DAGK in detergent micelles, the in situ MAS-NMR data illustrated that
      (19)F chemical shift values of residues at different membrane protein locations
      were influenced by interactions between membrane proteins and their surrounding
      lipid or lipid mimic environments, while (19)F side chain longitudinal relaxation
      values were probably affected by different interactions of DAGK with planar lipid
      bilayer versus globular detergent micelles.

PMID- 22362704
TI  - Competitive cellular uptake of nanoparticles made from polystyrene, poly(methyl
      methacrylate), and polylactide.
AB  - The uptake behavior of negatively charged fluorescent nanoparticles made from
      different polymers (PS, PMMA, and PLLA) is studied on HeLa cells. All particles
      are obtained by the miniemulsion process using sodium dodecylsulfate as anionic
      surfactant. The size of the particles is in the range 105-125 nm. Cell uptake is
      analyzed by flow cytometry and reveals a higher uptake of PLLA particles compared
      to PMMA and PS particles. In competitive uptake studies two different types of
      particles are co-incubated with the HeLa cells; the results indicate a mutual
      influence of the particles on their uptake behavior. A reduced internalization of
      PLLA particles in the presence of PS particles is observed, although neither the
      co-incubation of PMMA and PLLA nor of PMMA and PS shows similar effect.

PMID- 22362705
TI  - Microgroove cushion of robotic endoscope for active locomotion in the
      gastrointestinal tract.
AB  - BACKGROUND: The robotic endoscope the advantage of active locomotion in the
      gastrointestinal (GI) tract, but lacks a suitable contact device to improve the
      locomotion efficiency and safety. METHODS: This paper proposes a microgroove
      cushion for the robotic endoscope to improve its active locomotion ability in the
      GI tract. Coupons with different microgrooves were designed and tested to verify
      the contact efficiency of the grooves. Based on experimental investigations,
      uniform oblique grid grooves were suggested, because they could generate gteater
      friction than other proposed microgrooves on the intestinal surface. To improve
      the contact safety of the robotic endoscope, a cushion-type contact device was
      designed and fabricated. The microgroove cushion was tested under the use of a
      custom-built robot. RESULTS: An experiment in a rigid tube showed that the robot
      with cushion had a static friction 65% higher than the robot without cushion; an
      experiment in the in vitro colonic tract showed that the robot without the
      cushion produced a more obvious contact appearance than with the cushion. It can
      be seen that the microgroove cushion provides the robotic endoscope with
      efficient and safe contact ability. CONCLUSIONS: The microgroove cushion is a
      useful addition to the development of a contact device for the robotic endoscope
      in the GI tract, although requiring further improvements.

PMID- 22362706
TI  - Platelet internalization within the cancer cells: what is the significance?

PMID- 22362707
TI  - Glycine to glutamic acid misincorporation observed in a recombinant protein
      expressed by Escherichia coli cells.
AB  - A novel amino acid misincorporation, in which the intended glycine (Gly) residues
      were replaced by a glutamic acid (Glu), was observed in a recombinant protein
      expressed by Escherichia coli. The misincorporation was identified by peptide
      mapping and liquid chromatography-tandem mass spectrometric analysis on
      proteolyzed peptides of the protein and verified using the corresponding
      synthetic peptides containing the misincorporated residues. Analysis of the
      distribution of the misincorporated residues and their codon usage shows strong
      correlation between this misincorporation and the use of rarely used codon within
      the E. coli expression system. Results in this study suggest that the usage of
      the rare codon GGA has resulted in a Glu for Gly misincorporation.

PMID- 22362708
TI  - Novel biodegradable and pH-sensitive poly(ester amide) microspheres for oral
      insulin delivery.
AB  - Biodegradable and pH-sensitive PEAs based on dual amino acids are designed,
      synthesized, and characterized. Insulin can be loaded into the PEA microspheres
      by a solid-in-oil-in-oil technique with high encapsulation efficiency. The
      feasibility of PEA microspheres as oral insulin delivery carriers is evaluated in
      vitro and in vivo. The hydrophobic leucine groups on PEA seem to play an
      important role in the pH-dependent release mechanism and cytotoxicity of PEA
      microspheres. Oral administration of insulin-loaded PEA microspheres to
      streptozotocin-induced diabetic rats at 60 IU kg(-1)  is able to reduce fasting
      plasma glucose levels to 49.4%. These results indicate that PEA microspheres are
      potential new vehicles for insulin oral delivery.

PMID- 22362709
TI  - Theoretical and experimental exploration of the energy landscape of the quasi
      binary cesium chloride/lithium chloride system.
AB  - As a case study, the energy landscape of the cesium chloride/lithium chloride
      system was investigated by combining theoretical and experimental methods. Global
      optimization for many compositions of this quasi-binary system gave candidates
      for possible modifications that constitute promising targets for subsequent
      syntheses based on solid-state reactions. Owing to the synergetic and
      complementary nature of the computational and experimental approaches, a
      substantially better efficiency of exploration was achieved. Several new phases
      were found in this system, for the compositions CsLiCl(2) and CsLi(2)Cl(3), and
      their thermodynamic ranking with respect to the already-known phases was
      clarified. In particular, the new CsLiCl(2) modification was shown to be the low
      temperature phase, whilst the already-known modification for this composition
      corresponded to a high-temperature phase. Based on these results, an improved
      cesium chloride/lithium chloride phase diagram was derived, and this approach
      points the way to more rational and more efficient solid-state synthesis.

PMID- 22362710
TI  - Perinatal exposure to low doses of tributyltin chloride advances puberty and
      affects patterns of estrous cyclicity in female mice.
AB  - Tributyltin (TBT), a proven endocrine-disrupting chemical, is well known to
      induce imposex in female gastropods. Herein we demonstrate the effects of low
      doses of tributyltin chloride (TBTCl) on the female offspring of KM mice.
      Pregnant mice were administered by gavage with 0, 1, 10, or 100 MUg TBTCl/kg body
      weight/day from day 6 of pregnancy through the period of lactation. TBTCl
      dramatically advanced the age of onset of vaginal opening (VO) and first vaginal
      estrus, and reduced body weights at VO and first estrus. Furthermore, perinatal
      treatment with TBTCl significantly reduced the number of days between VO and
      first estrus. In addition, female offspring from dams exposed to 10 and 100 MUg
      kg(-1) TBTCl exhibited altered patterns of estrous cyclicity in adulthood. In
      conclusion, perinatal exposure to low doses TBTCl result in early puberty and
      impaired estrous cyclicity in female mice, which suggest that TBTCl might act as
      an estrogen agonist or/and a disruptor on hypothalamic-pituitary function in the
      present study.

PMID- 22362711
TI  - Intracellular and extracellular hyaline globules in endobronchial ultrasound
      guided transbronchial needle aspiration of mediastinal lymph node: a clue for the
      diagnosis of metastatic hepatocellular carcinoma.

PMID- 22362712
TI  - Inositol phosphate-induced stabilization of inositol 1,3,4,5,6-pentakisphosphate
      2-kinase and its role in substrate specificity.
AB  - Inositol phosphate kinases (IPKs) sequentially phosphorylate inositol phosphates
      (IPs) on their inositol rings to yield an array of signaling molecules. IPKs must
      possess the ability to recognize their physiological substrates from among a pool
      of over 30 cellular IPs that differ in numbers and positions of phosphates.
      Crystal structures from IPK subfamilies have revealed structural determinants for
      IP discrimination, which vary considerably between IPKs. However, recent
      structures of inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPK1) did not reveal
      how IPK1 selectively recognizes its physiological substrate, IP5, while excluding
      others. Here, we report that limited proteolysis has revealed the presence of
      multiple conformational states in the IPK1 catalytic cycle, with notable
      protection from protease only in the presence of IP. Further, a 3.1-A crystal
      structure of IPK1 bound to ADP in the absence of IP revealed decreased order in
      residues 110-140 within the N-lobe of the kinase compared with structures in
      which IP is bound. Using this solution and crystallographic data, we propose a
      model for recognition of IP substrate by IPK1 wherein phosphate groups at the 4-,
      5-, and 6-positions are recognized initially by the C-lobe with subsequent
      interaction of the 1-position phosphate by Arg130 that stabilizes this residue
      and the N-lobe. This model explains how IPK1 can be highly specific for a single
      IP substrate by linking its interactions with substrate phosphate groups to the
      stabilization of the N- and C-lobes and kinase activation.

PMID- 22362713
TI  - Preparation of biodegradable polylactide microparticles via a biocompatible
      procedure.
AB  - PLA MPs are prepared via a novel and toxic-chemical-free fabrication route using
      ethyl lactate, a green solvent and FDA-approved aroma. MPs are obtained by a
      solution jet break-up and solvent displacement method. Adjusting flow parameters
      allows the tuning of MPs size between 60 and 180 um, with reduced polydispersity.
      Morphological analysis shows microporous particles with Janus-like surface. A
      fluorophore is successfully loaded into the MPs during their formation step. This
      versatile green solvent-based procedure is proven to be suitable for drug
      encapsulation and delivery applications. The method may be extended to different
      droplet generation techniques.

PMID- 22362714
TI  - Downregulation and antiproliferative role of FHL3 in breast cancer.
AB  - Four and a half LIM domain (FHL) protein 3 is a member of the FHL protein family
      that plays roles in the regulation of signal transduction, cell adhesion,
      survival, and mobility. FHL3 has been implicated in the development and
      progression of liver cancer. However, the biological function of FHL3 in other
      cancers remains unclear. Here, we show that FHL3 is downregulated in breast
      cancer patients. Using small interfering RNA (siRNA) knockdown and/or
      overexpression experiments, we demonstrated that FHL3 suppressed anchorage
      dependent and -independent growth of human breast cancer cells. The
      antiproliferative effects of FHL3 on breast cancer cell growth were associated
      with both the G1 and the G2/M cell cycle arrest, which was accompanied by a
      marked inhibition of the G1-phase marker cyclin D1 and the G2/M-phase marker
      cyclin B1 as well as the induction of the cyclin dependent kinase inhibitor p21
      (WAF1/CIP1), a negative regulator of cell cycle progression at G1 and G2. These
      results suggest that FHL3 may play a role in the development and progression of
      breast cancer, and thereby may be a potential target for human breast cancer gene
      therapy.

PMID- 22362715
TI  - Curcumin inhibits the migration and invasion of mouse hepatoma Hca-F cells
      through down-regulating caveolin-1 expression and epidermal growth factor
      receptor signaling.
AB  - Mouse hepatoma cellular carinoma cell line (Hca-F) cells have highly invasive and
      lymphatic metastasis potential in vitro and in vivo. Curcumin (diferuloylmethane)
      is an active component of the spice turmeric and has a diversity of antitumor
      activities. However, there is no available information to address the effects of
      curcumin on migration and invasion of mouse hepatoma Hca-F cells. In this study,
      we found that curcumin exerted a concentration- and time-dependent inhibitory
      effect on the migration and invasion of Hca-F cells in vitro. Curcumin inhibited
      the expression of the tumor promoter caveolin-1 (Cav-1) in Hca-F cells. Up
      regulation of Cav-1 expression by pcDNA3.1/Cav-1 plasmid was able to reverse the
      curcumin-induced antimigration and anti-invasion effects in vitro. Curcumin down
      regulated the expression of cluster of differntiation (CD)147, matrix
      metalloproteinase 2, and matrix metalloproteinase 9 and inhibited the
      phosphorylation of epidermal growth factor receptor (EGFR), the phosphoinositilde
      3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase
      (MAPK), and p44/42MAPK in Hca-F cells. Taken together, our findings suggest that
      curcumin can suppress the migratory and invasive ability of mouse hepatoma Hca-F
      cells, and this action is mediated through a novel mechanism involving
      inactivation of Cav-1 and EGFR signaling pathways.

PMID- 22362717
TI  - Fine-needle aspiration of metastatic papillary thyroid carcinoma found in the
      liver.
AB  - Papillary thyroid carcinoma (PTC) metastasis to the liver is a rare event and may
      cause diagnostic dilemmas. In this study, we have reviewed the cytological
      features of metastatic PTC to the liver, tested the BRAF V600E status of these
      lesions, and discussed potential diagnostic pitfalls. The pathological archives
      at the Johns Hopkins Hospital were searched for metastatic PTC. A total of 247
      cases were identified; four cases were found to have metastases to the liver.
      Three of these cases were available for molecular testing to determine BRAF V600E
      status. All patients were female with ages ranging from 39- to 66-years old.
      Local lymph node involvement was found in all patients at the time of
      thyroidectomy. The average time of liver metastasis discovery following
      thyroidectomy was 16 years. The cytomorphology revealed predominantly microacini
      or two-dimensional clusters. Tumor cells were small-to-intermediate in size with
      oval nuclei, fine chromatin, nuclear grooves, rare intranuclear pseudoinclusions,
      and mitoses. In all cases, immunohistochemical stains for thyroglobulin and
      thyroid transcription factor 1 (TTF-1) were positive. All these tested cases were
      negative for the BRAF V600E mutation. The differential diagnosis includes
      adenocarcinoma and neuroendocrine neoplasms. The most important morphologic
      features for diagnosing PTC are the presence of pale finely granular chromatin,
      nuclear grooves, and intranuclear pseudoinclusions. A thorough review of the
      patient's clinical history and the use of appropriate IHC stains are essential in
      reaching an accurate diagnosis. Further molecular characterization is necessary
      to identify the changes most strongly associated with distant metastasis.

PMID- 22362718
TI  - Impact of clinical pharmacist interventions in reducing paediatric prescribing
      errors.
AB  - OBJECTIVE: To assess the impact of pharmacist intervention in reducing
      prescribing errors in paediatrics, and to analyse the clinical significance and
      reasons behind the errors detected. METHODS: Cross-sectional epidemiological
      study analysing the activities of the paediatric pharmacist in a maternity and
      children's hospital with 180 paediatric beds, between January 2007 and December
      2009. The following variables were analysed: impact of the pharmacist's
      recommendation on patient care, reason for the intervention, clinical
      significance, type of negative outcome associated with the medication, acceptance
      rate, medication involved, intervention detection date and observations. RESULTS:
      A total of 1475 interventions in medical orders for 14,713 paediatric patients
      were recorded (40 (2.9%) extremely significant interventions and 155 (11.1%) very
      significant interventions). There were 1357 prescribing errors, 833 of which were
      dosing errors. 2.2% of the errors detected were potentially fatal (30 cases) and
      14.3% (194 cases) were clinically serious. The main reason for interventions was
      detection of a dosage between 1.5 and 10 times higher than that recommended. The
      overall rate of acceptance of the pharmacist's suggestions was 94.3%. The
      pharmacist carried out an average of 0.019 interventions per patient day
      throughout the study period. CONCLUSION: Interventions by a clinical pharmacist
      had a major impact on reducing prescribing errors in the study period, thus
      improving the quality and safety of care provided.

PMID- 22362719
TI  - Ethics bureaucracy: a significant hurdle for collaborative follow-up of drug
      effectiveness in rare childhood diseases.

PMID- 22362720
TI  - Lung aerosol deposition in suckling infants.
AB  - INTRODUCTION: Aerosol therapy in infants may be greatly compromised by face mask
      rejection due to squirming and crying. Lung aerosol deposition in crying infants
      may thereby be greatly reduced. Since 'suckling' on a pacifier calms infants,
      they should more readily accept a face mask that incorporates a pacifier.
      However, since infants must breathe nasally while suckling, lung aerosol
      deposition may be reduced due to impaction in the nose. The aim of the present
      pilot study was to compare lung aerosol deposition while suckling on a pacifier
      incorporated into a mask with that obtained while inhaling from a conventional
      mask. METHODS: Twelve infants <12 months old and who regularly used pacifiers
      participated as their own controls. Lung aerosol deposition was measured
      scintigraphically (technetium-(99m)DTPA-labelled normal saline aerosol, MMAD
      (Mass Median Aerodynamic Diameter) 3 um and GSD (Geometric Standard Deviation) of
      2) via jet nebuliser using a conventional mask versus 'suckling' on their
      pacifier incorporated into a unique mask. RESULTS: Mean lung deposition (+/- SD)
      while suckling using a mask with attached pacifier (1.6 +/- 0.5% in the right
      lung) was similar to that with a conventional mask (1.7 +/- 0.9%, p=0.81).
      CONCLUSIONS: Lung aerosol deposition during nasal breathing while suckling on a
      pacifier-equipped mask is similar to that in infants breathing quietly using a
      conventional mask, and results comparable with previous data in infants and in
      nasal breathing models of an infant's upper respiratory tract. Using a pacifier
      during aerosol treatment in infants may be as efficient as conventional treatment
      without a pacifier.

PMID- 22362721
TI  - Management of gastroenteritis over 10 years: changing culture and maintaining the
      change.
AB  - OBJECTIVE: To examine the impact of an implementation program on adherence to a
      guideline for the management of acute gastroenteritis. DESIGN: Using four
      retrospective audits over a 10-year period, the authors examined the change in
      practice and maintenance of that change following a targeted implementation
      program for the clinical guideline. SETTING: Tertiary children's hospital in
      South Wales. PARTICIPANTS: 447 children aged less than 5 years, admitted to
      hospital with acute gastroenteritis, comprising four cross-sectional samples (106
      in 1999, 153 in 2002, 99 in 2004, 89 in 2009). MAIN OUTCOME MEASURES: Age of
      child, hydration status, method of rehydration and duration of admission, for
      each audit, with an implementation strategy delivered after the second audit.
      RESULTS: In 1999 and 2002, intravenous rehydration was used in 20% and 15% of
      cases, respectively. After the implementation program in 2004, compared to 1999,
      there was a significant decrease in the intravenous rehydration rate to 4% in
      2004 (p<0.001); in 2009 the intravenous rehydration rate was maintained at a low
      level of 6% (p<0.001). CONCLUSION: It was only after the implementation program
      that a change in practice was achieved. Once change had been accepted, it was
      maintained even in the absence of targeted training. Audit does not improve
      clinical practice unless, in addition, there is a clear, succinct guideline with
      an implementation programme in place.

PMID- 22362722
TI  - Is severe obesity a cardiovascular health concern in the Inuit population?
AB  - OBJECTIVES: Obesity is rising globally and severe obesity (SO) [body mass index
      (BMI) = 40 kg/m(2) or = 35 kg/m(2) with co-morbidity] is growing at a much faster
      rate. Amongst the Inuit, evolution of SO remains unknown. We investigated whether
      the level of SO changed and whether the cardio-metabolic profile improved or
      deteriorated in Nunavik Inuit between 1992 and 2004. METHODS: SO subjects were
      selected from two comparable population-based studies. These studies were
      undertaken in Nunavik (Quebec, Canada), and were performed in two different time
      frames, separated by 12 years. Physiological (lipid profile, fasting insulin,
      fasting glucose, and blood pressure) as well as anthropometric data (BMI, waist
      circumference, and waist to hip ratio) were collected in both studies. RESUTLS:
      There was approximately a fourfold increase in the prevalence of SO in comparable
      age groups. This increase affected both genders between 1992 and 2004. Smoking
      rates in SO populations have significantly decreased during this period, from 85%
      to 41% (P < 0.0001). Overall, there were no statistically significant differences
      in the cardio-metabolic profile (insulin, total cholesterol, LDL-cholesterol, HDL
      cholesterol, triglycerides, systolic and diastolic blood pressures, BMI, and
      waist to hip ratio). There was, however, a significant increase in waist
      circumference (P < 0.001), especially in women (P < 0.01). Type 2 diabetes
      remained stable, at around 40% in this population. CONCLUSION: Although the
      prevalence of SO increased, the cardio-metabolic profile remained stable.
      Nevertheless, regular monitoring of chronic disease in this population remains
      crucial.

PMID- 22362723
TI  - Compulsion: the key to US health care reform.
AB  - To meet the twin goals of cost containment and universal coverage, health care
      legislators in the US will eventually have to come to grips with the concept of
      'compulsion'. This is the main tenet of this paper, which also addresses what
      compulsion might mean as applied in the context of recent US health care
      legislation and its implications for the US health care industry. Missing the
      opportunity to embrace compulsion more fully may lead to cost containment not
      being achieved, thus threatening the sustainability of the reforms contained in
      the recently Patient Protection and Affordable Care Act.

PMID- 22362724
TI  - To be a round peg in a square hole.

PMID- 22362725
TI  - Overlap of hospital use and social care in older people in England.
AB  - OBJECTIVES: To link pseudonymous health and social care use data in order to
      determine what proportion of older people access hospital and social care
      services. METHODS: Retrospective analysis of linked, pseudonymous, routine
      service use data of people aged 75 and over (n = 133,055) drawn from the
      operational systems of four primary care trusts and their corresponding local
      authorities in England. RESULTS: Fourteen percent of older people received local
      authority-funded social care in one year, 59% accessed NHS hospital care and 10%
      accessed both types of service. Most people using social care also used a
      hospital service (71%). This was a higher proportion than for people who did not
      use social care services (57%, P < 0.001). However, the use of hospitals varied
      by type of social care such that the residents of care homes had fewer admissions
      to hospital, fewer Accident and Emergency attendances and fewer outpatient visits
      than people receiving high intensity home care. CONCLUSIONS: Using routine data
      from large populations, we have demonstrated interactions in the use of hospital
      care and social care for older people. Residents of care homes tend to use
      hospitals less frequently than people receiving home care. More detailed work is
      required to explain this phenomenon.

PMID- 22362726
TI  - Current advances in Phi29 pRNA biology and its application in drug delivery.
AB  - Bacteriophage 29 (Phi29) packaging RNA (pRNA) is one of the key components in the
      viral DNA-packaging motor. It contains two functional domains facilitating the
      translocation of DNA into the viral capsid by interacting with other elements in
      the motor and promoting adenosine triphosphates hydrolysis. Through the
      connection between interlocking loops in adjacent pRNA monomers, pRNA functions
      in the form of multimer ring in the motor. Previous studies have addressed the
      unique structure and conformation of pRNA. However, there are different DNA
      packaging models proposed for the viral genome transportation mechanism. The DNA
      packaging ability and the unique features of pRNA have been attracting efforts to
      study its potential applications in nanotechnology. The pRNA has been proved to
      be a promising tool for delivering nucleic acid-based therapeutic molecules by
      covalent linkage with ribozymes, small interfering RNAs, aptamers, and artificial
      microRNAs. The flexibility in constructing dimers, trimers, and hexamers enables
      the assembly of polyvalent nanoparticles to carry drug molecules for therapeutic
      purposes, cell ligands for target delivery, image detector for drug entry
      monitoring, and endosome disrupter for drug release. Besides these fascinating
      pharmacological advantages, pRNA-based drug delivery has also been demonstrated
      to prolong the drug half life with minimal induction of immune response and
      toxicity.

PMID- 22362727
TI  - Taller Indian women are more successful at the marriage market.
AB  - OBJECTIVES: Whereas being tall has consistently been found a favorable
      characteristic at the marriage market for men, much less is known about the
      association between stature and marital success among women. Taller women are
      healthier than shorter women, give birth more easily and their offspring are
      healthier. We therefore would expect them to be more successful at the marriage
      market. However, existing evidence is mixed. We study the association between
      women's height and the odds of being married, marrying young, experiencing a
      divorce, and becoming widowed, and the association between women's height and
      their husbands' educational attainment and occupational status. METHODS: Data
      come from the Indian National Family Health Survey 2005-2006, a representative
      study among 124,385 women and 74,369 men in all Indian states. Effects of female
      height on being married, marrying young, divorce, widowhood, and husband's
      occupation were estimated using logistic regression models. Effects of female
      height on husband's education were estimated using OLS regression models. Woman's
      education and age were always taken into account. Where possible controls for
      husband's height, husband's education, and age at marriage were included.
      RESULTS: Positive effects of women's height on favorable marital outcomes were
      found. Taller than average women are more likely to marry, get higher educated
      husbands with better jobs and are less likely to marry at a very young age or to
      lose their husbands through divorce or premature death. CONCLUSIONS: Taller
      Indian women seem to be more successful at the marriage market.

PMID- 22362729
TI  - Human brain mass: similar body composition associations as observed across
      mammals.
AB  - OBJECTIVES: A classic association is the link between brain mass and body mass
      across mammals that has now been shown to derive from fat-free mass (FFM) and not
      fat mass (FM). This study aimed to establish for the first time the associations
      between human brain mass and body composition and to compare these relations with
      those established for liver as a reference organ. METHODS: Subjects were 112 men
      and 148 women who had brain and liver mass measured by magnetic resonance imaging
      with FM and FFM measured by dual-energy X-ray absorptiometry. RESULTS: Brain mass
      scaled to height (H) with powers of <=0.6 in men and women; liver mass and FFM
      both scaled similarly as H(~2) . The fraction of FFM as brain thus scaled
      inversely to height (P < 0.001) while liver mass/FFM was independent of height.
      After controlling for age, brain, and liver mass were associated with FFM while
      liver was additionally associated with FM (all models P <= 0.01). After
      controlling for age and sex, FFM accounted for ~5% of the variance in brain mass
      while levels were substantially higher for liver mass (~60%). Brain mass was
      significantly larger (P < 0.001) in men than in women, even after controlling for
      age and FFM. CONCLUSIONS: As across mammals, human brain mass associates
      significantly, although weakly, with FFM and not FM; the fraction of FFM as brain
      relates inversely to height; brain differs in these relations from liver, another
      small high metabolic rate organ; and the sexual dimorphism in brain mass persists
      even after adjusting for age and FFM.

PMID- 22362728
TI  - MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular
      carcinoma.
AB  - The deregulation of microRNA (miRNA) is frequently associated with a variety of
      cancers, including hepatocellular carcinoma (HCC). In this study, we identified
      10 upregulated miRNAs (miR-217, miR-518b, miR-517c, miR-520g, miR-519a, miR-522,
      miR-518e, miR-525-3p, miR-512-3p and miR-518a-3p) and 10 downregulated miRNAs
      (miR-138, miR-214, miR-214#, miR-27a#, miR-199a-5p, miR-433, miR-511, miR-592,
      miR-483-5p and miR-483-3p) by Taqman miRNAs array and quantitative real-time PCR
      (qRT-PCR) confirmation. Additionally, we investigated the expression and possible
      role of miR-138 in HCC. qRT-PCR results showed that miR-138 was downregulated in
      77.8%(14/18) of HCC tissues compared with adjacent non-tumor tissues.
      Overexpression of miR-138 reduced cell viability and colony formation by
      induction of cell arrest in HCC cell lines and inhibited tumor cell growth in
      xenograft nude mice. The use of miR-138 inhibitor increased cell viability and
      colony formation in HCC cell lines and tumor cell growth in xenograft nude mice.
      Using TargetScan predictions, CCND3 was defined as a potential direct target of
      miR-138. Furthermore, CCND3 protein expression was observed to be negatively
      correlated with miR-138 expression in HCC tissues. The dual-luciferase reporter
      gene assay results showed that CCND3 was a direct target of miR-138. The use of
      miR-138 mimic or inhibitor could decrease or increase CCND3 protein levels in HCC
      cell lines. We conclude that the frequently downregulated miR-138 can regulate
      CCND3 and function as a tumor suppressor in HCC. Therefore, miR-138 may serve as
      a useful therapeutic agent for miRNA-based HCC therapy.

PMID- 22362730
TI  - Unrecognized sequence homologies may confound genome-wide association studies.
AB  - Genome-wide association studies (GWAS) have become a preferred method to identify
      new genetic susceptibility loci. This technique aims to understanding the
      molecular etiology of common diseases, but in many cases, it has led to the
      identification of loci with no obvious biological relevance. Herein, we show that
      previously unrecognized sequence homologies have caused single-nucleotide
      polymorphism (SNP) microarrays to incorrectly associate a phenotype to a given
      locus when in fact the linkage is to another distant locus. Using genetic
      differences between male and female subjects as a model to study the effect of
      one specific genomic region on the whole SNP microarray, we provide strong
      evidence that the use of standard methods for GWAS can be misleading. We suggest
      a new systematic quality control step in the biological interpretation of
      previous and future GWAS.

PMID- 22362731
TI  - Binding of the 5'-untranslated region of coronavirus RNA to zinc finger CCHC-type
      and RNA-binding motif 1 enhances viral replication and transcription.
AB  - Coronaviruses RNA synthesis occurs in the cytoplasm and is regulated by host cell
      proteins. In a screen based on a yeast three-hybrid system using the 5'
      untranslated region (5'-UTR) of SARS coronavirus (SARS-CoV) RNA as bait against a
      human cDNA library derived from HeLa cells, we found a positive candidate
      cellular protein, zinc finger CCHC-type and RNA-binding motif 1 (MADP1), to be
      able to interact with this region of the SARS-CoV genome. This interaction was
      subsequently confirmed in coronavirus infectious bronchitis virus (IBV). The
      specificity of the interaction between MADP1 and the 5'-UTR of IBV was
      investigated and confirmed by using an RNA pull-down assay. The RNA-binding
      domain was mapped to the N-terminal region of MADP1 and the protein binding
      sequence to stem-loop I of IBV 5'-UTR. MADP1 was found to be translocated to the
      cytoplasm and partially co-localized with the viral replicase/transcriptase
      complexes (RTCs) in IBV-infected cells, deviating from its usual nuclear
      localization in a normal cell using indirect immunofluorescence. Using small
      interfering RNA (siRNA) against MADP1, defective viral RNA synthesis was observed
      in the knockdown cells, therefore indicating the importance of the protein in
      coronaviral RNA synthesis.

PMID- 22362732
TI  - Effective stiffening of DNA due to nematic ordering causes DNA molecules packed
      in phage capsids to preferentially form torus knots.
AB  - Observation that DNA molecules in bacteriophage capsids preferentially form torus
      type of knots provided a sensitive gauge to evaluate various models of DNA
      arrangement in phage heads. Only models resulting in a preponderance of torus
      knots could be considered as close to reality. Recent studies revealed that
      experimentally observed enrichment of torus knots can be qualitatively reproduced
      in numerical simulations that include a potential inducing nematic arrangement of
      tightly packed DNA molecules within phage capsids. Here, we investigate what
      aspects of the nematic arrangement are crucial for inducing formation of torus
      knots. Our results indicate that the effective stiffening of DNA by the nematic
      arrangement not only promotes knotting in general but is also the decisive factor
      in promoting formation of DNA torus knots in phage capsids.

PMID- 22362733
TI  - Gemin5 proteolysis reveals a novel motif to identify L protease targets.
AB  - Translation of picornavirus RNA is governed by the internal ribosome entry site
      (IRES) element, directing the synthesis of a single polyprotein. Processing of
      the polyprotein is performed by viral proteases that also recognize as substrates
      host factors. Among these substrates are translation initiation factors and RNA
      binding proteins whose cleavage is responsible for inactivation of cellular gene
      expression. Foot-and-mouth disease virus (FMDV) encodes two proteases, L(pro) and
      3C(pro). Widespread definition of L(pro) targets suffers from the lack of a
      sufficient number of characterized substrates. Here, we report the proteolysis of
      the IRES-binding protein Gemin5 in FMDV-infected cells, but not in cells infected
      by other picornaviruses. Proteolysis was specifically associated with expression
      of L(pro), yielding two stable products, p85 and p57. In silico search of
      putative L targets within Gemin5 identified two sequences whose potential
      recognition was in agreement with proteolysis products observed in infected
      cells. Mutational analysis revealed a novel L(pro) target sequence that included
      the RKAR motif. Confirming this result, the Fas-ligand Daxx, was proteolysed in
      FMDV-infected and L(pro)-expressing cells. This protein carries a RRLR motif
      whose substitution to EELR abrogated L(pro) recognition. Thus, the sequence
      (R)(R/K)(L/A)(R) defines a novel motif to identify putative targets of L(pro) in
      host factors.

PMID- 22362734
TI  - Structure of the bifunctional methyltransferase YcbY (RlmKL) that adds the
      m7G2069 and m2G2445 modifications in Escherichia coli 23S rRNA.
AB  - The 23S rRNA nucleotide m(2)G2445 is highly conserved in bacteria, and in
      Escherichia coli this modification is added by the enzyme YcbY. With lengths of
      around 700 amino acids, YcbY orthologs are the largest rRNA methyltransferases
      identified in Gram-negative bacteria, and they appear to be fusions from two
      separate proteins found in Gram-positives. The crystal structures described here
      show that both the N- and C-terminal halves of E. coli YcbY have a
      methyltransferase active site and their folding patterns respectively resemble
      the Streptococcus mutans proteins Smu472 and Smu776. Mass spectrometric analyses
      of 23S rRNAs showed that the N-terminal region of YcbY and Smu472 are
      functionally equivalent and add the m(2)G2445 modification, while the C-terminal
      region of YcbY is responsible for the m(7)G2069 methylation on the opposite side
      of the same helix (H74). Smu776 does not target G2069, and this nucleotide
      remains unmodified in Gram-positive rRNAs. The E.coli YcbY enzyme is the first
      example of a methyltransferase catalyzing two mechanistically different types of
      RNA modification, and has been renamed as the Ribosomal large subunit
      methyltransferase, RlmKL. Our structural and functional data provide insights
      into how this bifunctional enzyme evolved.

PMID- 22362735
TI  - Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament,
      explaining stimulatory effect on gene recombination.
AB  - Human RAD51 protein (HsRad51) catalyses the DNA strand exchange reaction for
      homologous recombination. To clarify the molecular mechanism of the reaction in
      vitro being more effective in the presence of Ca(2+) than of Mg(2+), we have
      investigated the effect of these ions on the structure of HsRad51 filament
      complexes with single- and double-stranded DNA, the reaction intermediates. Flow
      linear dichroism spectroscopy shows that the two ionic conditions induce
      significantly different structures in the HsRad51/single-stranded DNA complex,
      while the HsRad51/double-stranded DNA complex does not demonstrate this ionic
      dependence. In the HsRad51/single-stranded DNA filament, the primary intermediate
      of the strand exchange reaction, ATP/Ca(2+) induces an ordered conformation of
      DNA, with preferentially perpendicular orientation of nucleobases relative to the
      filament axis, while the presence of ATP/Mg(2+), ADP/Mg(2+) or ADP/Ca(2+) does
      not. A high strand exchange activity is observed for the filament formed with
      ATP/Ca(2+), whereas the other filaments exhibit lower activity. Molecular
      modelling suggests that the structural variation is caused by the divalent cation
      interfering with the L2 loop close to the DNA-binding site. It is proposed that
      the larger Ca(2+) stabilizes the loop conformation and thereby the protein-DNA
      interaction. A tight binding of DNA, with bases perpendicularly oriented, could
      facilitate strand exchange.

PMID- 22362736
TI  - Recruitment of the ATP-dependent chromatin remodeler dMi-2 to the transcribed
      region of active heat shock genes.
AB  - The ATP-dependent chromatin remodeler dMi-2 can play both positive and negative
      roles in gene transcription. Recently, we have shown that dMi-2 is recruited to
      the hsp70 gene in a heat shock-dependent manner, and is required to achieve high
      transcript levels. Here, we use chromatin immunoprecipitation sequencing (ChIP
      Seq) to identify other chromatin regions displaying increased dMi-2 binding upon
      heat shock and to characterize the distribution of dMi-2 over heat shock genes.
      We show that dMi-2 is recruited to the body of at least seven heat shock genes.
      Interestingly, dMi-2 binding extends several hundred base pairs beyond the
      polyadenylation site into the region where transcriptional termination occurs. We
      find that dMi-2 does not associate with the entire nucleosome-depleted hsp70
      locus 87A. Rather, dMi-2 binding is restricted to transcribed regions. Our
      results suggest that dMi-2 distribution over active heat shock genes are
      determined by transcriptional activity.

PMID- 22362737
TI  - Recognition and potential mechanisms for replication and erasure of cytosine
      hydroxymethylation.
AB  - Cytosine residues in mammalian DNA occur in at least three forms, cytosine (C), 5
      methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC). During semi
      conservative DNA replication, hemi-methylated (M/C) and hemi-hydroxymethylated
      (H/C) CpG dinucleotides are transiently generated, where only the parental strand
      is modified and the daughter strand contains native cytosine. Here, we explore
      the role of DNA methyltransferases (DNMT) and ten eleven translocation (Tet)
      proteins in perpetuating these states after replication, and the molecular basis
      of their recognition by methyl-CpG-binding domain (MBD) proteins. Using
      recombinant proteins and modified double-stranded deoxyoligonucleotides, we show
      that DNMT1 prefers a hemi-methylated (M/C) substrate (by a factor of >60) over
      hemi-hydroxymethylated (H/C) and unmodified (C/C) sites, whereas both DNMT3A and
      DNMT3B have approximately equal activity on all three substrates (C/C, M/C and
      H/C). Binding of MBD proteins to methylated DNA inhibited Tet1 activity,
      suggesting that MBD binding may also play a role in regulating the levels of
      5hmC. All five MBD proteins generally have reduced binding affinity for 5hmC
      relative to 5mC in the fully modified context (H/M versus M/M), though their
      relative abilities to distinguish the two varied considerably. We further show
      that the deamination product of 5hmC could be excised by thymine DNA glycosylase
      and MBD4 glycosylases regardless of context.

PMID- 22362738
TI  - Structural architecture of the human long non-coding RNA, steroid receptor RNA
      activator.
AB  - While functional roles of several long non-coding RNAs (lncRNAs) have been
      determined, the molecular mechanisms are not well understood. Here, we report the
      first experimentally derived secondary structure of a human lncRNA, the steroid
      receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA
      that coactivates several human sex hormone receptors and is strongly associated
      with breast cancer. Coding isoforms of SRA are also expressed to produce
      proteins, making the SRA gene a unique bifunctional system. Our experimental
      findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a
      complex structural organization, consisting of four domains, with a variety of
      secondary structure elements. We examine the coevolution of the SRA gene at the
      RNA structure and protein structure levels using comparative sequence analysis
      across vertebrates. Rapid evolutionary stabilization of RNA structure, combined
      with frame-disrupting mutations in conserved regions, suggests that evolutionary
      pressure preserves the RNA structural core rather than its translational product.
      We perform similar experiments on alternatively spliced SRA isoforms to assess
      their structural features.

PMID- 22362739
TI  - Junctions between i-motif tetramers in supramolecular structures.
AB  - The symmetry of i-motif tetramers gives to cytidine-rich oligonucleotides the
      capacity to associate into supramolecular structures (sms). In order to determine
      how the tetramers are linked together in such structures, we have measured by gel
      filtration chromatography and NMR the formation and dissociation kinetics of sms
      built by oligonucleotides containing two short C stretches separated by a non
      cytidine-base. We show that a stretch of only two cytidines either at the 3'- or
      5'-end is long enough to link the tetramers into sms. The analysis of the
      properties of sms formed by oligonucleotides differing by the length of the oligo
      C stretches, the sequence orientation and the nature of the non-C base provides a
      model of the junction connecting the tetramers in sms.

PMID- 22362740
TI  - Interaction of human telomeric DNA with N-methyl mesoporphyrin IX.
AB  - The remarkable selectivity of N-methyl mesoporphyrin IX (NMM) for G-quadruplexes
      (GQs) is long known, however its ability to stabilize and bind GQs has not been
      investigated in detail. Through the use of circular dichroism, UV-visible
      spectroscopy and fluorescence resonance energy transfer (FRET) melting assay we
      have shown that NMM stabilizes human telomeric DNA dAG(3)(TTAG(3))(3) (Tel22) and
      is selective for its parallel conformation to which it binds in 1:1 stoichiometry
      with a binding constant of ~ 1.0 * 10(5)M(-1). NMM does not interact with an
      antiparallel conformation of Tel22 in sodium buffer and is the second example in
      the literature, after TOxaPy, of a ligand with an excellent selectivity for a
      specific GQ structure. NMM's stabilizing ability toward predominantly parallel GQ
      conformation is universal: it stabilizes a variety of biologically relevant G
      rich sequences including telomeres and oncogene promoters. The N-methyl group is
      integral for selectivity and stabilization, as the unmethylated analogue,
      mesoporphyrin IX, does not stabilize GQ DNA in FRET melting assays. Finally, NMM
      induces the isomerization of Tel22 into a structure with increased parallel
      component in K(+) but not in Na(+) buffer. The ability of NMM to cause structural
      rearrangement and efficient stabilization of Tel22 may bear biological
      significance.

PMID- 22362741
TI  - Chemical and biological approaches to improve the efficiency of homologous
      recombination in human cells mediated by artificial restriction DNA cutter.
AB  - A chemistry-based artificial restriction DNA cutter (ARCUT) was recently prepared
      from Ce(IV)/EDTA complex and a pair of pseudo-complementary peptide nucleic
      acids. This cutter has freely tunable scission-site and site specificity. In this
      article, homologous recombination (HR) in human cells was promoted by cutting a
      substrate DNA with ARCUT, and the efficiency of this bioprocess was optimized by
      various chemical and biological approaches. Of two kinds of terminal structure
      formed by ARCUT, 3'-overhang termini provided by 1.7-fold higher efficiency than
      5'-overhang termini. A longer homology length (e.g. 698 bp) was about 2-fold more
      favorable than shorter one (e.g. 100 bp). When the cell cycle was synchronized to
      G2/M phase with nocodazole, the HR was promoted by about 2-fold. Repression of
      the NHEJ-relevant proteins Ku70 and Ku80 by siRNA increased the efficiency by 2-
      to 3-fold. It was indicated that appropriate combination of all these chemical
      and biological approaches should be very effective to promote ARCUT-mediated HR
      in human cells.

PMID- 22362742
TI  - Regulation of AT1R expression through HuR by insulin.
AB  - Angiotensin II type 1 receptor (AT1R) has a pathophysiological role in
      hypertension, atherosclerosis and heart failure. Type 2 diabetes is
      hyperinsulinemic state and a major risk factor for atherosclerosis and
      hypertension. It is known that hyperinsulinemia upregulates AT1R expression post
      transcriptionally by increasing the half-life of AT1R mRNA, but little is known
      about the mechanism of this effect. In the present study, we first identified
      AT1R 3'-UTR as a mediator of insulin effect. Using 3'-UTR as a bait, we
      identified through analysis of insulin-stimulated cell lysates by affinity
      purification and mass spectrometry HuR as an insulin-regulated AT1R mRNA binding
      protein. By ribonucleoprotein immunoprecipitation, we found HuR binding to AT1R
      to be increased by insulin. Overexpression of HuR leads to increased AT1R
      expression in a 3'-UTR-dependent manner. Both insulin and HuR overexpression
      stabilize AT1R 3'-UTR and their responsive element within 3'-UTR are located
      within the same region. Cell fractionation demonstrated that insulin induced HuR
      translocation from nucleus to cytoplasm increased HuR binding to cytoplasmic AT1R
      3'-UTR. Consistent with HuR translocation playing a mechanistic role in HuR
      effect, a reduction in the cytoplasmic levels of HuR either by silencing of HuR
      expression or by inhibition of HuR translocation into cytoplasm attenuated
      insulin response. These results show that HuR translocation to cytoplasm is
      enhanced by insulin leading to AT1R upregulation through HuR-mediated
      stabilization of AT1R mRNA.

PMID- 22362743
TI  - HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation
      from the target RNA.
AB  - The microRNA (miRNA)-mediated repression of protein synthesis in mammalian cells
      is a reversible process. Target mRNAs with regulatory AU-rich elements (AREs) in
      their 3'-untranslated regions (3'-UTR) can be relieved of miRNA repression under
      cellular stress in a process involving the embryonic lethal and altered vision
      family ARE-binding protein HuR. The HuR-mediated derepression occurred even when
      AREs were positioned at a considerable distance from the miRNA sites raising
      questions about the mechanism of HuR action. Here, we show that the relief of
      miRNA-mediated repression involving HuR can be recapitulated in different in
      vitro systems in the absence of stress, indicating that HuR alone is sufficient
      to relieve the miRNA repression upon binding to RNA ARE. Using in vitro assays
      with purified miRISC and recombinant HuR and its mutants, we show that HuR,
      likely by its property to oligomerize along RNA, leads to the dissociation of
      miRISC from target RNA even when miRISC and HuR binding sites are positioned at a
      distance. Further, we demonstrate that HuR association with AREs can also inhibit
      miRNA-mediated deadenylation of mRNA in the Krebs-2 ascites extract, in a manner
      likewise depending on the potential of HuR to oligomerize.

PMID- 22362744
TI  - MicroRNA and transcription factor co-regulatory network analysis reveals miR-19
      inhibits CYLD in T-cell acute lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological
      malignancy. The understanding of its gene expression regulation and molecular
      mechanisms still remains elusive. Started from experimentally verified T-ALL
      related miRNAs and genes, we obtained 120 feed-forward loops (FFLs) among T-ALL
      related genes, miRNAs and TFs through combining target prediction. Afterwards, a
      T-ALL miRNA and TF co-regulatory network was constructed, and its significance
      was tested by statistical methods. Four miRNAs in the miR-17-92 cluster and four
      important genes (CYLD, HOXA9, BCL2L11 and RUNX1) were found as hubs in the
      network. Particularly, we found that miR-19 was highly expressed in T-ALL
      patients and cell lines. Ectopic expression of miR-19 represses CYLD expression,
      while miR-19 inhibitor treatment induces CYLD protein expression and decreases NF
      kappaB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF
      kappaB form a regulatory FFL, which provides new clues for sustained activation
      of NF-kappaB in T-ALL. Taken together, we provided the first miRNA-TF co
      regulatory network in T-ALL and proposed a model to demonstrate the roles of miR
      19 and CYLD in the T-cell leukemogenesis. This study may provide potential
      therapeutic targets for T-ALL and shed light on combining bioinformatics with
      experiments in the research of complex diseases.

PMID- 22362745
TI  - DNA looping by FokI: the impact of synapse geometry on loop topology at varied
      site orientations.
AB  - Most restriction endonucleases, including FokI, interact with two copies of their
      recognition sequence before cutting DNA. On DNA with two sites they act in cis
      looping out the intervening DNA. While many restriction enzymes operate
      symmetrically at palindromic sites, FokI acts asymmetrically at a non-palindromic
      site. The directionality of its sequence means that two FokI sites can be bridged
      in either parallel or anti-parallel alignments. Here we show by biochemical and
      single-molecule biophysical methods that FokI aligns two recognition sites on
      separate DNA molecules in parallel and that the parallel arrangement holds for
      sites in the same DNA regardless of whether they are in inverted or repeated
      orientations. The parallel arrangement dictates the topology of the loop trapped
      between sites in cis: the loop from inverted sites has a simple 180 degrees 
      bend, while that with repeated sites has a convoluted 360 degrees  turn. The
      ability of FokI to act at asymmetric sites thus enabled us to identify the
      synapse geometry for sites in trans and in cis, which in turn revealed the
      relationship between synapse geometry and loop topology.

PMID- 22362746
TI  - Post-transcriptional homeostasis and regulation of MCM2-7 in mammalian cells.
AB  - The MiniChromosome Maintenance 2-7 (MCM2-7) complex provides essential
      replicative helicase function. Insufficient MCMs impair the cell cycle and cause
      genomic instability (GIN), leading to cancer and developmental defects in mice.
      Remarkably, depletion or mutation of one Mcm can decrease all Mcm levels. Here,
      we use mice and cells bearing a GIN-causing hypomophic allele of Mcm4 (Chaos3),
      in conjunction with disruption alleles of other Mcms, to reveal two new
      mechanisms that regulate MCM protein levels and pre-RC formation. First, the
      Mcm4(Chaos3) allele, which disrupts MCM4:MCM6 interaction, triggers a Dicer1 and
      Drosha-dependent ~ 40% reduction in Mcm2-7 mRNAs. The decreases in Mcm mRNAs
      coincide with up-regulation of the miR-34 family of microRNAs, which is known to
      be Trp53-regulated and target Mcms. Second, MCM3 acts as a negative regulator of
      the MCM2-7 helicase in vivo by complexing with MCM5 in a manner dependent upon a
      nuclear-export signal-like domain, blocking the recruitment of MCMs onto
      chromatin. Therefore, the stoichiometry of MCM components and their localization
      is controlled post-transcriptionally at both the mRNA and protein levels.
      Alterations to these pathways cause significant defects in cell growth reflected
      by disease phenotypes in mice.

PMID- 22362747
TI  - Investigating the entire course of telithromycin binding to Escherichia coli
      ribosomes.
AB  - Applying kinetics and footprinting analysis, we show that telithromycin, a
      ketolide antibiotic, binds to Escherichia coli ribosomes in a two-step process.
      During the first, rapidly equilibrated step, telithromycin binds to a low
      affinity site (K(T) = 500 nM), in which the lactone ring is positioned at the
      upper portion of the peptide exit tunnel, while the alkyl-aryl side chain of the
      drug inserts a groove formed by nucleotides A789 and U790 of 23S rRNA. During the
      second step, telithromycin shifts slowly to a high-affinity site (K(T)* = 8.33
      nM), in which the lactone ring remains essentially at the same position, while
      the side chain interacts with the base pair U2609:A752 and the extended loop of
      protein L22. Consistently, mutations perturbing either the base pair U2609:A752
      or the L22-loop hinder shifting of telithromycin to the final position, without
      affecting the initial step of binding. In contrast, mutation Lys63Glu in protein
      L4 placed on the opposite side of the tunnel, exerts only a minor effect on
      telithromycin binding. Polyamines disfavor both sequential steps of binding. Our
      data correlate well with recent crystallographic data and rationalize the changes
      in the accessibility of ribosomes to telithromycin in response to ribosomal
      mutations and ionic changes.

PMID- 22362748
TI  - Nsi1 plays a significant role in the silencing of ribosomal DNA in Saccharomyces
      cerevisiae.
AB  - In eukaryotic cells, ribosomal DNA (rDNA) forms the basis of the nucleolus. In
      Saccharomyces cerevisiae, 100-200 copies of a 9.1-kb rDNA repeat exist as a
      tandem array on chromosome XII. The stability of this highly repetitive array is
      maintained through silencing. However, the precise mechanisms that regulate rDNA
      silencing are poorly understood. Here, we report that S. cerevisiae Ydr026c,
      which we name NTS1 silencing protein 1 (Nsi1), plays a significant role in rDNA
      silencing. By studying the subcellular localization of 159 nucleolar proteins, we
      identified 11 proteins whose localization pattern is similar to that of Net1, a
      well-established rDNA silencing factor. Among these proteins is Nsi1, which is
      associated with the NTS1 region of rDNA and is required for rDNA silencing at
      NTS1. In addition, Nsi1 physically interacts with the known rDNA silencing
      factors Net1, Sir2 and Fob1. The loss of Nsi1 decreases the association of Sir2
      with NTS1 and increases histone acetylation at NTS1. Furthermore, Nsi1
      contributes to the longevity of yeast cells. Taken together, our findings suggest
      that Nsi1 is a new rDNA silencing factor that contributes to rDNA stability and
      lifespan extension in S. cerevisiae.

PMID- 22362749
TI  - Retinoic acid and androgen receptors combine to achieve tissue specific control
      of human prostatic transglutaminase expression: a novel regulatory network with
      broader significance.
AB  - In the human prostate, expression of prostate-specific genes is known to be
      directly regulated by the androgen-induced stimulation of the androgen receptor
      (AR). However, less is known about the expression control of the prostate
      restricted TGM4 (hTGP) gene. In the present study we demonstrate that the
      regulation of the hTGP gene depends mainly on retinoic acid (RA). We provide
      evidence that the retinoic acid receptor gamma (RAR-G) plays a major role in the
      regulation of the hTGP gene and that presence of the AR, but not its
      transcriptional transactivation activity, is critical for hTGP transcription. RA
      and androgen responsive elements (RARE and ARE) were mapped to the hTGP promoter
      by chromatin immunoprecipitation (ChIP), which also indicated that the active ARE
      and RARE sites were adjacent, suggesting that the antagonistic effect of androgen
      and RA is related to the relative position of binding sites. Publicly available
      AR and RAR ChIP-seq data was used to find gene potentially regulated by AR and
      RAR. Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and
      AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically
      regulated by androgens and RA confirming that this regulation is not particular
      of hTGP.

PMID- 22362750
TI  - A pentatricopeptide repeat protein acts as a site-specificity factor at multiple
      RNA editing sites with unrelated cis-acting elements in plastids.
AB  - In plant organelles, RNA editing alters specific cytidine residues to uridine in
      transcripts. All of the site-specificity factors of RNA editing identified so far
      are pentatricopeptide repeat (PPR) proteins. A defect in a specific PPR protein
      often impairs RNA editing at multiple sites, at which the cis-acting elements are
      not highly conserved. The molecular mechanism for sharing a single PPR protein
      over multiple sites is still unclear. We focused here on the PPR proteins OTP82
      and CRR22, the putative target elements of which are, respectively, partially and
      barely conserved. Recombinant OTP82 specifically bound to the -15 to 0 regions of
      its target sites. Recombinant CRR22 specifically bound to the -20 to 0 regions of
      the ndhB-7 and ndhD-5 sites and to the -17 to 0 region of the rpoB-3 site. Taking
      this information together with the genetic data, we conclude that OTP82 and CRR22
      act as site-specificity factors at multiple sites in plastids. In addition, the
      high-affinity binding of CRR22 to unrelated cis-acting elements suggests that
      only certain specific nucleotides in a cis-acting element are sufficient for high
      affinity binding of a PPR protein. The cis-acting elements can therefore be
      rather divergent and still be recognized by a single PPR protein.

PMID- 22362751
TI  - Crystal structures of the tRNA:m2G6 methyltransferase Trm14/TrmN from two domains
      of life.
AB  - Methyltransferases (MTases) form a major class of tRNA-modifying enzymes needed
      for the proper functioning of tRNA. Recently, RNA MTases from the TrmN/Trm14
      family that are present in Archaea, Bacteria and Eukaryota have been shown to
      specifically modify tRNA(Phe) at guanosine 6 in the tRNA acceptor stem. Here, we
      report the first X-ray crystal structures of the tRNA m(2)G6 (N(2)
      methylguanosine) MTase (TTC)TrmN from Thermus thermophilus and its ortholog
      (Pf)Trm14 from Pyrococcus furiosus. Structures of (Pf)Trm14 were solved in
      complex with the methyl donor S-adenosyl-l-methionine (SAM or AdoMet), as well as
      the reaction product S-adenosyl-homocysteine (SAH or AdoHcy) and the inhibitor
      sinefungin. (TTC)TrmN and (Pf)Trm14 consist of an N-terminal THUMP domain fused
      to a catalytic Rossmann-fold MTase (RFM) domain. These results represent the
      first crystallographic structure analysis of proteins containing both THUMP and
      RFM domain, and hence provide further insight in the contribution of the THUMP
      domain in tRNA recognition and catalysis. Electrostatics and conservation
      calculations suggest a main tRNA binding surface in a groove between the THUMP
      domain and the MTase domain. This is further supported by a docking model of TrmN
      in complex with tRNA(Phe) of T. thermophilus and via site-directed mutagenesis.

PMID- 22362752
TI  - miR-212/132 expression and functions: within and beyond the neuronal compartment.
AB  - During the last two decades, microRNAs (miRNAs) emerged as critical regulators of
      gene expression. By modulating the expression of numerous target mRNAs mainly at
      the post-transcriptional level, these small non-coding RNAs have been involved in
      most, if not all, biological processes as well as in the pathogenesis of a number
      of diseases. miR-132 and miR-212 are tandem miRNAs whose expression is necessary
      for the proper development, maturation and function of neurons and whose
      deregulation is associated with several neurological disorders, such as
      Alzheimer's disease and tauopathies (neurodegenerative diseases resulting from
      the pathological aggregation of tau protein in the human brain). Although their
      involvement in neuronal functions is the most described, evidences point towards
      a role of these miRNAs in many other biological processes, including inflammation
      and immune functions. Incidentally, miR-132 was recently classified as a
      'neurimmiR', a class of miRNAs operating within and between the neural and immune
      compartments. In this review, we propose an outline of the current knowledge
      about miR-132 and miR-212 functions in neurons and immune cells, by describing
      the signalling pathways and transcription factors regulating their expression as
      well as their putative or demonstrated roles and validated mRNA targets.

PMID- 22362753
TI  - Function of homo- and hetero-oligomers of human nucleoplasmin/nucleophosmin
      family proteins NPM1, NPM2 and NPM3 during sperm chromatin remodeling.
AB  - Sperm chromatin remodeling after oocyte entry is the essential step that
      initiates embryogenesis. This reaction involves the removal of sperm-specific
      basic proteins and chromatin assembly with histones. In mammals, three
      nucleoplasmin/nucleophosmin (NPM) family proteins-NPM1, NPM2 and NPM3-expressed
      in oocytes are presumed to cooperatively regulate sperm chromatin remodeling. We
      characterized the sperm chromatin decondensation and nucleosome assembly
      activities of three human NPM proteins. NPM1 and NPM2 mediated nucleosome
      assembly independently of other NPM proteins, whereas the function of NPM3 was
      largely dependent on formation of a complex with NPM1. Maximal sperm chromatin
      remodeling activity of NPM2 required the inhibition of its non-specific nucleic
      acid-binding activity by phosphorylation. Furthermore, the oligomer formation
      with NPM1 elicited NPM3 nucleosome assembly and sperm chromatin decondensation
      activity. NPM3 also suppressed the RNA-binding activity of NPM1, which enhanced
      the nucleoplasm-nucleolus shuttling of NPM1 in somatic cell nuclei. Our results
      proposed a novel mechanism whereby three NPM proteins cooperatively regulate
      chromatin disassembly and assembly in the early embryo and in somatic cells.

PMID- 22362754
TI  - A fast ab-initio method for predicting miRNA precursors in genomes.
AB  - miRNAs are small non coding RNA structures which play important roles in
      biological processes. Finding miRNA precursors in genomes is therefore an
      important task, where computational methods are required. The goal of these
      methods is to select potential pre-miRNAs which could be validated by
      experimental methods. With the new generation of sequencing techniques, it is
      important to have fast algorithms that are able to treat whole genomes in
      acceptable times. We developed an algorithm based on an original method where an
      approximation of miRNA hairpins are first searched, before reconstituting the pre
      miRNA structure. The approximation step allows a substantial decrease in the
      number of possibilities and thus the time required for searching. Our method was
      tested on different genomic sequences, and was compared with CID-miRNA, miRPara
      and VMir. It gives in almost all cases better sensitivity and selectivity. It is
      faster than CID-miRNA, miRPara and VMir: it takes ~ 30 s to process a 1 MB
      sequence, when VMir takes 30 min, miRPara takes 20 h and CID-miRNA takes 55 h. We
      present here a fast ab-initio algorithm for searching for pre-miRNA precursors in
      genomes, called miRNAFold. miRNAFold is available at http://EvryRNA.ibisc.univ
      evry.fr/.

PMID- 22362755
TI  - Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear
      receptor SHP.
AB  - Dnmt1 is frequently overexpressed in cancers, which contributes significantly to
      cancer-associated epigenetic silencing of tumor suppressor genes. However, the
      mechanism of Dnmt1 overexpression remains elusive. Herein, we elucidate a pathway
      through which nuclear receptor SHP inhibits zinc-dependent induction of Dnmt1 by
      antagonizing metal-responsive transcription factor-1 (MTF-1). Zinc treatment
      induces Dnmt1 transcription by increasing the occupancy of MTF-1 on the Dnmt1
      promoter while decreasing SHP expression. SHP in turn represses MTF-1 expression
      and abolishes zinc-mediated changes in the chromatin configuration of the Dnmt1
      promoter. Dnmt1 expression is increased in SHP-knockout (sko) mice but decreased
      in SHP-transgenic (stg) mice. In human hepatocellular carcinoma (HCC), increased
      DNMT1 expression is negatively correlated with SHP levels. Our study provides a
      molecular explanation for increased Dnmt1 expression in HCC and highlights SHP as
      a potential therapeutic target.

PMID- 22362756
TI  - The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in
      non-discriminating aspartyl-tRNA synthetase safeguards the genetic code.
AB  - Helicobacter pylori catalyzes Asn-tRNA(Asn) formation by use of the indirect
      pathway that involves charging of Asp onto tRNA(Asn) by a non-discriminating
      aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp
      into Asn by the GatCAB amidotransferase. We show that the partners of
      asparaginylation assemble into a dynamic Asn-transamidosome, which uses a
      different strategy than the Gln-transamidosome to prevent the release of the
      mischarged aminoacyl-tRNA intermediate. The complex is described by gel
      filtration, dynamic light scattering and kinetic measurements. Two strategies for
      asparaginylation are shown: (i) tRNA(Asn) binds GatCAB first, allowing
      aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii)
      tRNA(Asn) is bound by ND-AspRS which releases the Asp-tRNA(Asn) product much
      slower than the cognate Asp-tRNA(Asp); this kinetic peculiarity allows GatCAB to
      bind and transamidate Asp-tRNA(Asn) before its release by the ND-AspRS. These
      results are discussed in the context of the interrelation between the Asn and Gln
      transamidosomes which use the same GatCAB in H. pylori, and shed light on a
      kinetic mechanism that ensures faithful codon reassignment for Asn.

PMID- 22362758
TI  - Substrate-immobilized HIV-1 Tat drives VEGFR2/alpha(v)beta(3)-integrin complex
      formation and polarization in endothelial cells.
AB  - OBJECTIVE: The HIV-1 transactivating factor (Tat) possesses features typical of
      both cell-adhesive and angiogenic growth factor (AGF) proteins, inducing
      endothelial cell (EC) adhesion and proangiogenic activation. Tat was exploited to
      investigate the events triggered by EC adhesion to substrate-bound AGF that lead
      to proangiogenic activation. METHODS AND RESULTS: Immobilized Tat induces actin
      cytoskeleton organization, formation of alpha(v)beta(3) integrin(+)focal adhesion
      plaques, and recruitment of vascular endothelial growth factor receptor-2
      (VEGFR2) in the ventral plasma membrane of adherent ECs. Also, acceptor
      photobleaching fluorescence resonance energy transfer demonstrated that
      VEGFR2/alpha(v)beta(3) coupling occurs at the basal aspect of Tat-adherent ECs.
      Cell membrane fractionation showed that a limited fraction of alpha(v)beta(3)
      integrin and VEGFR2 does colocalize in lipid rafts at the basal aspect of Tat
      adherent ECs. VEGFR2 undergoes phosphorylation and triggers pp60src/ERK(1/2)
      activation. The use of lipid raft disrupting agents and second messenger
      inhibitors demonstrated that intact lipid rafts and the VEGFR2/pp60src/ERK(1/2)
      pathway are both required for cytoskeleton organization and proangiogenic
      activation of Tat-adherent ECs. CONCLUSIONS: Substrate-immobilized Tat causes
      VEGFR2/alpha(v)beta(3) complex formation and polarization at the basal aspect of
      adherent ECs, VEGFR2/pp60src/ERK(1/2) phosphorylation, cytoskeleton organization,
      and proangiogenic activation. These results provide novel insights in the
      AGF/tyrosine kinase receptor/integrin cross-talk.

PMID- 22362757
TI  - Double threading through DNA: NMR structural study of a bis-naphthalene
      macrocycle bound to a thymine-thymine mismatch.
AB  - The macrocyclic bis-naphthalene macrocycle (2,7-BisNP), belonging to the
      cyclobisintercalator family of DNA ligands, recognizes T-T mismatch sites in
      duplex DNA with high affinity and selectivity, as evidenced by thermal
      denaturation experiments and NMR titrations. The binding of this macrocycle to an
      11-mer DNA oligonucleotide containing a T-T mismatch was studied using NMR
      spectroscopy and NMR-restrained molecular modeling. The ligand forms a single
      type of complex with the DNA, in which one of the naphthalene rings of the ligand
      occupies the place of one of the mismatched thymines, which is flipped out of the
      duplex. The second naphthalene unit of the ligand intercalates at the A-T base
      pair flanking the mismatch site, leading to encapsulation of its thymine residue
      via double stacking. The polyammonium linking chains of the macrocycle are
      located in the minor and the major grooves of the oligonucleotide and participate
      in the stabilization of the complex by formation of hydrogen bonds with the
      encapsulated thymine base and the mismatched thymine remaining inside the helix.
      The study highlights the uniqueness of this cyclobisintercalation binding mode
      and its importance for recognition of DNA lesion sites by small molecules.

PMID- 22362760
TI  - Antithrombin-independent effects of heparins on fibrin clot nanostructure.
AB  - OBJECTIVE: Because of the widespread clinical use of heparins, their effects on
      the enzymatic cascade are very well known. In contrast, little is known about the
      direct effect of heparins on the nanostructure of fibrin fibers, even though this
      nanostructure plays a major role in the mechanical strength and lysis of clots.
      This lack of reliable data can be correlated with the lack of a nonintrusive,
      quantitative method to determine this structure. We recently developed such a
      method that allows the simultaneous determination of the average fiber radius and
      the protein content using spectrometric data. In this study, we assessed the
      nanostructure of fibrin in a system composed of human thrombin and fibrinogen.
      METHODS AND RESULTS: We provide quantitative evidence showing that both
      unfractionated heparin and low molecular weight heparin directly alter the
      nanostructure of fibrin fibers independent of their other actions on the
      coagulation cascade; as expected, the pentasaccharide fondaparinux has no effect.
      CONCLUSIONS: Our results show that in addition to the effect of heparin on the
      coagulation cascade, modifications of the fibrin nanostructure may also
      contribute to improved fibrinolysis.

PMID- 22362759
TI  - Protein kinase C isoform epsilon negatively regulates ADP-induced calcium
      mobilization and thromboxane generation in platelets.
AB  - OBJECTIVE: Members of the protein kinase C (PKC) family are shown to positively
      and negatively regulate platelet activation. Although positive regulatory roles
      are extensively studied, negative regulatory roles of PKCs are poorly understood.
      We investigated the mechanism and specific isoforms involved in PKC-mediated
      negative regulation of ADP-induced functional responses. METHODS AND RESULTS: A
      pan-PKC inhibitor, GF109203X, potentiated ADP-induced cPLA(2) phosphorylation and
      thromboxane generation as well as ERK activation and intracellular calcium
      (Ca(2+)(i)) mobilization, 2 signaling molecules, upstream of cPLA(2) activation.
      Thus, PKCs inhibit cPLA(2) activation by inhibiting ERK and Ca(2+)(i)
      mobilization. Because the inhibitor of classic PKC isoforms, GO-6976, did not
      affect ADP-mediated thromboxane generation, we investigated the role of novel
      class of PKC isoforms. ADP-induced thromboxane generation, calcium mobilization,
      and ERK phosphorylation were potentiated in PKCepsilon null murine platelets
      compared with platelets from wild-type littermates. Interestingly, when
      thromboxane release is blocked, ADP-induced aggregation in PKCepsilon knockout
      and wild-type was similar, suggesting that PKCepsilon does not affect ADP-induced
      aggregation directly. PKCepsilon knockout mice exhibited shorter times to
      occlusion in an FeCl(3)-induced arterial injury model and shorter bleeding times
      in tail-bleeding experiments. CONCLUSIONS: We conclude that PKCepsilon negatively
      regulates ADP-induced thromboxane generation in platelets and offers protection
      against thrombosis.

PMID- 22362761
TI  - Structural and functional studies of trans-encoded HLA-DQ2.3
      (DQA1*03:01/DQB1*02:01) protein molecule.
AB  - MHC class II molecules are composed of one alpha-chain and one beta-chain whose
      membrane distal interface forms the peptide binding groove. Most of the existing
      knowledge on MHC class II molecules comes from the cis-encoded variants where the
      alpha- and beta-chain are encoded on the same chromosome. However, trans-encoded
      class II MHC molecules, where the alpha- and beta-chain are encoded on opposite
      chromosomes, can also be expressed. We have studied the trans-encoded class II
      HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention
      as it may explain the increased risk of certain individuals to type 1 diabetes.
      We report the x-ray crystal structure of this HLA molecule complexed with a
      gluten epitope at 3.05 A resolution. The gluten epitope, which is the only known
      HLA-DQ2.3-restricted epitope, is preferentially recognized in the context of the
      DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease
      patient. This preferential recognition can be explained by improved HLA binding
      as the epitope combines the peptide-binding motif of DQ2.5 (negative charge at
      P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3
      together with all other available DQ crystal structures and sequences led us to
      categorize DQA1 and DQB1 genes into two groups where any alpha-chain and beta
      chain belonging to the same group are expected to form a stable heterodimer.

PMID- 22362762
TI  - Inhibiting alternative pathway complement activation by targeting the factor D
      exosite.
AB  - By virtue of its amplifying property, the alternative complement pathway has been
      implicated in a number of inflammatory diseases and constitutes an attractive
      therapeutic target. An anti-factor D Fab fragment (AFD) was generated to inhibit
      the alternative complement pathway in advanced dry age-related macular
      degeneration. AFD potently prevented factor D (FD)-mediated proteolytic
      activation of its macromolecular substrate C3bB, but not proteolysis of a small
      synthetic substrate, indicating that AFD did not block access of the substrate to
      the catalytic site. The crystal structures of AFD in complex with human and
      cynomolgus FD (at 2.4 and 2.3 A, respectively) revealed the molecular details of
      the inhibitory mechanism. The structures show that the AFD-binding site includes
      surface loops of FD that form part of the FD exosite. Thus, AFD inhibits FD
      proteolytic function by interfering with macromolecular substrate access rather
      than by inhibiting FD catalysis, providing the molecular basis of AFD-mediated
      inhibition of a rate-limiting step in the alternative complement pathway.

PMID- 22362763
TI  - Single-stranded DNA scanning and deamination by APOBEC3G cytidine deaminase at
      single molecule resolution.
AB  - APOBEC3G (Apo3G) is a single-stranded (ss)DNA cytosine deaminase that eliminates
      HIV-1 infectivity by converting C -> U in numerous small target motifs on the
      minus viral cDNA. Apo3G deaminates linear ssDNA in vitro with pronounced spatial
      asymmetry favoring the 3' -> 5' direction. A similar polarity observed in vivo is
      believed responsible for initiating localized C -> T mutational gradients that
      inactivate the virus. When compared with double-stranded (ds)DNA scanning
      enzymes, e.g. DNA glycosylases that excise rare aberrant bases, there is a
      paucity of mechanistic studies on ssDNA scanning enzymes. Here, we investigate
      ssDNA scanning and motif-targeting mechanisms for Apo3G using single molecule
      Forster resonance energy transfer. We address the specific issue of deamination
      asymmetry within the general context of ssDNA scanning mechanisms and show that
      Apo3G scanning trajectories, ssDNA contraction, and deamination efficiencies
      depend on motif sequence, location, and ionic strength. Notably, we observe the
      presence of bidirectional quasi-localized scanning of Apo3G occurring proximal to
      a 5' hot motif, a motif-dependent DNA contraction greatest for 5' hot > 3' hot >
      5' cold motifs, and diminished mobility at low salt. We discuss the single
      molecule Forster resonance energy transfer data in terms of a model in which
      deamination polarity occurs as a consequence of Apo3G binding to ssDNA in two
      orientations, one that is catalytically favorable, with the other disfavorable.

PMID- 22362764
TI  - Allele-specific differences in activity of a novel cannabinoid receptor 1 (CNR1)
      gene intronic enhancer in hypothalamus, dorsal root ganglia, and hippocampus.
AB  - Polymorphisms within intron 2 of the CNR1 gene, which encodes cannabinoid
      receptor 1 (CB(1)), have been associated with addiction, obesity, and brain
      volume deficits. We used comparative genomics to identify a polymorphic
      (rs9444584-C/T) sequence (ECR1) in intron 2 of the CNR1 gene that had been
      conserved for 310 million years. The C-allele of ECR1 (ECR1(C)) acted as an
      enhancer in hypothalamic and dorsal root ganglia cells and responded to MAPK
      activation through the MEKK pathway but not in hippocampal cells. However,
      ECR1(T) was significantly more active in hypothalamic and dorsal root ganglia
      cells but, significantly, and in contrast to ECR1(C), was highly active in
      hippocampal cells where it also responded strongly to activation of MAPK.
      Intriguingly, rs9444584 is in strong linkage disequilibrium with two other SNPs
      (rs9450898 (r(2) = 0.841) and rs2023239 (r(2) = 0.920)) that have been associated
      with addiction, obesity (rs2023239), and reduced fronto-temporal white matter
      volumes in schizophrenia patients as a result of cannabis misuse (rs9450898).
      Considering their high linkage disequilibrium and the increased response of
      ECR1(T) to MAPK signaling when compared with ECR1(C), it is possible that the
      functional effects of the different alleles of rs9444584 may play a role in the
      conditions associated with rs9450898 and rs2023239. Further analysis of the
      different alleles of ECR1 may lead to a greater understanding of the role of CNR1
      gene misregulation in these conditions as well as chronic inflammatory pain.

PMID- 22362765
TI  - A monoclonal antibody directed against a conformational epitope of the HIV-1
      trans-activator (Tat) protein neutralizes cross-clade.
AB  - The identification of a neutralizing mAb against extracellular HIV-1
      transactivator of transcription (Tat) is important for the development of an
      efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not
      only for HIV-1 replication but also as an extracellular toxin able to disrupt the
      immune system. We showed previously that immunization of rabbits with Tat Oyi, a
      variant cloned from an African woman who did not develop AIDS following HIV-1
      infection, raised antibodies able to recognize different Tat variants. We carried
      out mice immunization with Tat Oyi and selected a mAb named 7G12, which had the
      capacity to cross-recognize heterologous Tat variants by a common three
      dimensional epitope. These results highlighted that Tat variants were able to
      acquire a structure, in contrast to a number of studies showing Tat as an
      unfolded protein. mAb 7G12 also had the capacity to neutralize the biological
      activities of these Tat variants by blocking the cellular uptake of extracellular
      Tat. This is the first study using Tat Oyi to produce a mAb able to neutralize
      effectively activities of extracellular Tats from different HIV-1 subtypes. This
      mAb has an important potential in therapeutic passive immunization and could help
      HIV-1 infected patients to restore their immunity.

PMID- 22362766
TI  - A bridging [4Fe-4S] cluster and nucleotide binding are essential for function of
      the Cfd1-Nbp35 complex as a scaffold in iron-sulfur protein maturation.
AB  - The essential P-loop NTPases Cfd1 and Nbp35 of the cytosolic iron-sulfur (Fe-S)
      protein assembly machinery perform a scaffold function for Fe-S cluster
      synthesis. Both proteins contain a nucleotide binding motif of unknown function
      and a C-terminal motif with four conserved cysteine residues. The latter motif
      defines the Mrp/Nbp35 subclass of P-loop NTPases and is suspected to be involved
      in transient Fe-S cluster binding. To elucidate the function of these two motifs,
      we first created cysteine mutant proteins of Cfd1 and Nbp35 and investigated the
      consequences of these mutations by genetic, cell biological, biochemical, and
      spectroscopic approaches. The two central cysteine residues (CPXC) of the C
      terminal motif were found to be crucial for cell viability, protein function,
      coordination of a labile [4Fe-4S] cluster, and Cfd1-Nbp35 hetero-tetramer
      formation. Surprisingly, the two proximal cysteine residues were dispensable for
      all these functions, despite their strict evolutionary conservation. Several
      lines of evidence suggest that the C-terminal CPXC motifs of Cfd1-Nbp35
      coordinate a bridging [4Fe-4S] cluster. Upon mutation of the nucleotide binding
      motifs Fe-S clusters could no longer be assembled on these proteins unless wild
      type copies of Cfd1 and Nbp35 were present in trans. This result indicated that
      Fe-S cluster loading on these scaffold proteins is a nucleotide-dependent step.
      We propose that the bridging coordination of the C-terminal Fe-S cluster may be
      ideal for its facile assembly, labile binding, and efficient transfer to target
      Fe-S apoproteins, a step facilitated by the cytosolic iron-sulfur (Fe-S) protein
      assembly proteins Nar1 and Cia1 in vivo.

PMID- 22362767
TI  - Intermediate domain of receptor-interacting protein kinase 1 (RIPK1) determines
      switch between necroptosis and RIPK1 kinase-dependent apoptosis.
AB  - Receptor-interacting protein kinase 1 (RIPK1) is an important component of the
      tumor necrosis factor receptor 1 (TNFR1) signaling pathway. Depending on the cell
      type and conditions, RIPK1 mediates MAPK and NF-kappaB activation as well as cell
      death. Using a mutant form of RIPK1 (RIPK1DeltaID) lacking the intermediate
      domain (ID), we confirm the requirement of this domain for activation of these
      signaling events. Moreover, expression of RIPK1DeltaID resulted in enhanced
      recruitment of caspase-8 to the TNFR1 complex II component Fas-associated death
      domain (FADD), which allowed a shift from TNF-induced necroptosis to apoptosis in
      L929 cells. Addition of the RIPK1 kinase inhibitor necrostatin-1 strongly reduced
      recruitment of RIPK1 and caspase-8 to FADD and subsequent apoptosis, indicating a
      role for RIPK1 kinase activity in apoptotic complex formation. Our study shows
      that RIPK1 has an anti-apoptotic function residing in its ID and demonstrates a
      cellular system as an elegant genetic model for RIPK1 kinase-dependent apoptosis
      that, in contrast to the Smac mimetic model, does not rely on depletion of
      cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2).

PMID- 22362768
TI  - Identification of multicomponent histidine-aspartate phosphorelay system
      controlling flagellar and motility gene expression in Geobacter species.
AB  - Geobacter species play an important role in the natural biogeochemical cycles of
      aquatic sediments and subsurface environments as well as in subsurface
      bioremediation by oxidizing organic compounds with the reduction of insoluble
      Fe(III) oxides. Flagellum-based motility is considered to be critical for
      Geobacter species to locate fresh sources of Fe(III) oxides. Functional and
      comparative genomic approaches, coupled with genetic and biochemical methods,
      identified key regulators for flagellar gene expression in Geobacter species. A
      master transcriptional regulator, designated FgrM, is a member of the enhancer
      binding protein family. The fgrM gene in the most studied strain of Geobacter
      species, Geobacter sulfurreducens strain DL-1, is truncated by a transposase
      gene, preventing flagellar biosynthesis. Integrating a functional FgrM homolog
      restored flagellar biosynthesis and motility in G. sulfurreducens DL-1 and
      enhanced the ability to reduce insoluble Fe(III) oxide. Interrupting the fgrM
      gene in G. sulfurreducens strain KN400, which is motile, removed the capacity for
      flagellar production and inhibited Fe(III) oxide reduction. FgrM, which is also a
      response regulator of the two-component His-Asp phosphorelay system, was
      phosphorylated by histidine kinase GHK4, which was essential for flagellar
      production and motility. GHK4, which is a hybrid kinase with a receiver domain at
      the N terminus, was phosphorylated by another histidine kinase, GHK3. Therefore,
      the multicomponent His-Asp phosphorelay system appears to control flagellar gene
      expression in Geobacter species.

PMID- 22362769
TI  - Peroxisome proliferator-activated receptor beta/delta induces myogenesis by
      modulating myostatin activity.
AB  - Classically, peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) function was thought to be restricted to enhancing adipocyte
      differentiation and development of adipose-like cells from other lineages.
      However, recent studies have revealed a critical role for PPARbeta/delta during
      skeletal muscle growth and regeneration. Although PPARbeta/delta has been
      implicated in regulating myogenesis, little is presently known about the role
      and, for that matter, the mechanism(s) of action of PPARbeta/delta in regulating
      postnatal myogenesis. Here we report for the first time, using a PPARbeta/delta
      specific ligand (L165041) and the PPARbeta/delta-null mouse model, that
      PPARbeta/delta enhances postnatal myogenesis through increasing both myoblast
      proliferation and differentiation. In addition, we have identified Gasp-1 (growth
      and differentiation factor-associated serum protein-1) as a novel downstream
      target of PPARbeta/delta in skeletal muscle. In agreement, reduced Gasp-1
      expression was detected in PPARbeta/delta-null mice muscle tissue. We further
      report that a functional PPAR-responsive element within the 1.5-kb proximal Gasp
      1 promoter region is critical for PPARbeta/delta regulation of Gasp-1. Gasp-1 has
      been reported to bind to and inhibit the activity of myostatin; consistent with
      this, we found that enhanced secretion of Gasp-1, increased Gasp-1 myostatin
      interaction and significantly reduced myostatin activity upon L165041-mediated
      activation of PPARbeta/delta. Moreover, we analyzed the ability of hGASP-1 to
      regulate myogenesis independently of PPARbeta/delta activation. The results
      revealed that hGASP-1 protein treatment enhances myoblast proliferation and
      differentiation, whereas silencing of hGASP-1 results in defective myogenesis.
      Taken together these data revealed that PPARbeta/delta is a positive regulator of
      skeletal muscle myogenesis, which functions through negatively modulating
      myostatin activity via a mechanism involving Gasp-1.

PMID- 22362770
TI  - Structural and functional characterization of monomeric EphrinA1 binding site to
      EphA2 receptor.
AB  - The EphA2 receptor is overexpressed in glioblastoma multiforme and has been to
      shown to contribute to cell transformation, tumor initiation, progression, and
      maintenance. EphrinA1 (eA1) is a preferred ligand for the receptor. Treatment
      with monomeric eA1, the form of eA1 found in the extracellular environment,
      causes receptor phosphorylation, internalization, and down-regulation with
      subsequent anti-tumor effects. Here, we investigated the structure-function
      relationship of a monomeric eA1 focusing on its G-H loop
      ((108)FQRFTPFTLGKEFKE(123)G), a highly conserved region among eAs that mediates
      binding to their receptors. Alanine substitution mutants of the G-H loop amino
      acids were transfected into U-251 MG glioblastoma multiforme cells, and
      functional activity of each mutant in conditioned media was assessed by EphA2
      down-regulation, ERK and AKT activation and cellular response assays. Alanine
      substitutions at positions Pro-113 Thr-115, Gly-117, Glu-122, and also Gln-109
      enhanced the EphA2 receptor down-regulation and decreased p-ERK and p-AKT.
      Substitution mutants of eA1 at positions Phe-108, Arg-110, Phe-111, Thr-112, Phe
      114, Leu-116, Lys-118, Glu-119, and Phe-120 had a deleterious effect on EphA2
      down-regulation when compared with eA1-WT. Mutants at positions Phe-108, Lys-18,
      Lys-121, Gly-123 retained similar properties to eA1-WT. Recombinant eA1-R110A, 
      T115A, -G117A, and -F120A have been found to exhibit the same characteristics as
      the ligands contained in the conditioned media mainly due to the differences in
      their binding to the receptor. Thus, we have identified variants of eA1 that
      possess either superagonistic or antagonistic properties. These new findings will
      be important in the understanding of the receptor/ligand interactions and in
      further design of anti-cancer therapies targeting the eA/EphA system.

PMID- 22362771
TI  - The Amotl2 gene inhibits Wnt/beta-catenin signaling and regulates embryonic
      development in zebrafish.
AB  - The Motin family proteins can regulate cell polarity, cell mobility, and
      proliferation during embryonic development by controlling distinct signaling
      pathways. In this study, we demonstrate that amotl2 knockdown in zebrafish wild
      type embryos results in embryonic dorsalization, and this effect can be
      antagonized by co-knockdown of the dorsal inducer beta-catenin2. Overexpression
      of amotl2 in masterblind (mbl) homozygous embryos, in which canonical Wnt
      signaling is up-regulated due to an axin1 mutation, transforms eyeless phenotype
      into smaller eyes, whereas co-knockdown of amot, amotl1, and amotl2 leads to
      development of smaller eyes in mbl heterozygotes. In cultured mammalian cells,
      Motin family members all possess the ability to attenuate Wnt/beta-catenin
      signaling. Focusing on Amotl2, we show that Amotl2 can associate with and trap
      beta-catenin in the Rab11-positive recycling endosomes, and as a result, the
      amount of beta-catenin in the cytosol and nucleus is reduced. Thus, our findings
      provide novel insights into functions of Motin family members and regulation of
      Wnt/beta-catenin signaling.

PMID- 22362772
TI  - HIV/simian immunodeficiency virus (SIV) accessory virulence factor Vpx loads the
      host cell restriction factor SAMHD1 onto the E3 ubiquitin ligase complex
      CRL4DCAF1.
AB  - The sterile alpha motif and HD domain-containing protein-1 (SAMHD1) inhibits
      infection of myeloid cells by human and related primate immunodeficiency viruses
      (HIV and SIV). This potent inhibition is counteracted by the Vpx accessory
      virulence factor of HIV-2/SIVsm viruses, which targets SAMHD1 for proteasome
      dependent degradation, by reprogramming cellular CRL4(DCAF1) E3 ubiquitin ligase.
      However, the precise mechanism of Vpx-dependent recruitment of human SAMHD1 onto
      the ligase, and the molecular interfaces on the respective molecules have not
      been defined. Here, we show that human SAMHD1 is recruited to the CRL4(DCAF1-Vpx)
      E3 ubiquitin ligase complex by interacting with the DCAF1 substrate receptor
      subunit in a Vpx-dependent manner. No stable association is detectable with DCAF1
      alone. The SAMHD1 determinant for the interaction is a short peptide located
      distal to the SAMHD1 catalytic domain and requires the presence of Vpx for stable
      engagement. This peptide is sufficient to confer Vpx-dependent recruitment to
      CRL4(DCAF1) and ubiquitination when fused to heterologous proteins. The precise
      amino acid sequence of the peptide diverges among SAMHD1 proteins from different
      vertebrate species, explaining selective down-regulation of human SAMHD1 levels
      by Vpx. Critical amino acid residues of SAMHD1 and Vpx involved in the DCAF1-Vpx
      SAMDH1 interaction were identified by mutagenesis. Our findings show that the N
      terminus of Vpx, bound to DCAF1, recruits SAMHD1 via its C terminus to CRL4, in a
      species-specific manner for proteasomal degradation.

PMID- 22362773
TI  - Mapping precursor-binding site on TatC subunit of twin arginine-specific protein
      translocase by site-specific photo cross-linking.
AB  - A number of secreted precursor proteins of bacteria, archaea, and plant
      chloroplasts stand out by a conserved twin arginine-containing sequence motif in
      their signal peptides. Many of these precursor proteins are secreted in a
      completely folded conformation by specific twin arginine translocation (Tat)
      machineries. Tat machineries are high molecular mass complexes consisting of two
      types of membrane proteins, a hexahelical TatC protein, and usually one or two
      single-spanning membrane proteins, called TatA and TatB. TatC has previously been
      shown to be involved in the recognition of twin arginine signal peptides. We have
      performed an extensive site-specific cross-linking analysis of the Escherichia
      coli TatC protein under resting and translocating conditions. This strategy
      allowed us to map the recognition site for twin arginine signal peptides to the
      cytosolic N-terminal region and first cytosolic loop of TatC. In addition,
      discrete contact sites between TatC, TatB, and TatA were revealed. We discuss a
      tentative model of how a twin arginine signal sequence might be accommodated in
      the Tat translocase.

PMID- 22362774
TI  - Structure of Salmonella effector protein SopB N-terminal domain in complex with
      host Rho GTPase Cdc42.
AB  - SopB is a type III secreted Salmonella effector protein with phosphoinositide
      phosphatase activity and a distinct GTPase binding domain. The latter interacts
      with host Cdc42, an essential Rho GTPase that regulates critical events in
      eukaryotic cytoskeleton organization and membrane trafficking. Structural and
      biochemical analysis of the SopB GTPase binding domain in complex with Cdc42
      shows for the first time that SopB structurally and functionally mimics a host
      guanine nucleotide dissociation inhibitor (GDI) by contacting key residues in the
      regulatory switch regions of Cdc42 and slowing Cdc42 nucleotide exchange.

PMID- 22362775
TI  - Ferritin protein nanocage ion channels: gating by N-terminal extensions.
AB  - Ferritin protein nanocages, self-assembled from four-alpha-helix bundle subunits,
      use Fe(2+) and oxygen to synthesize encapsulated, ferric oxide minerals. Ferritin
      minerals are iron concentrates stored for cell growth. Ferritins are also
      antioxidants, scavenging Fenton chemistry reactants. Channels for iron entry and
      exit consist of helical hairpin segments surrounding the 3-fold symmetry axes of
      the ferritin nanocages. We now report structural differences caused by amino acid
      substitutions in the Fe(2+) ion entry and exit channels and at the cytoplasmic
      pores, from high resolution (1.3-1.8 A) protein crystal structures of the
      eukaryotic model ferritin, frog M. Mutations that eliminate conserved ionic or
      hydrophobic interactions between Arg-72 and Asp-122 and between Leu-110 and Leu
      134 increase flexibility in the ion channels, cytoplasmic pores, and/or the N
      terminal extensions of the helix bundles. Decreased ion binding in the channels
      and changes in ordered water are also observed. Protein structural changes
      coincide with increased Fe(2+) exit from dissolved, ferric minerals inside
      ferritin protein cages; Fe(2+) exit from ferritin cages depends on a complex,
      surface-limited process to reduce and dissolve the ferric mineral. High
      concentrations of bovine serum albumin or lysozyme (protein crowders) to mimic
      the cytoplasm restored Fe(2+) exit in the variants to wild type. The data suggest
      that fluctuations in pore structure control gating. The newly identified role of
      the ferritin subunit N-terminal extensions in gating Fe(2+) exit from the
      cytoplasmic pores strengthens the structural and functional analogies between
      ferritin ion channels in the water-soluble protein assembly and membrane protein
      ion channels gated by cytoplasmic N-terminal peptides.

PMID- 22362776
TI  - Environment of TyrZ in photosystem II from Thermosynechococcus elongatus in which
      PsbA2 is the D1 protein.
AB  - The main cofactors that determine the photosystem II (PSII) oxygen evolution
      activity are borne by the D1 and D2 subunits. In the cyanobacterium
      Thermosynechococcus elongatus, there are three psbA genes coding for D1. Among
      the 344 residues constituting D1, there are 21 substitutions between PsbA1 and
      PsbA3, 31 between PsbA1 and PsbA2, and 27 between PsbA2 and PsbA3. Here, we
      present the first study of PsbA2-PSII. Using EPR and UV-visible time-resolved
      absorption spectroscopy, we show that: (i) the time-resolved EPR spectrum of
      Tyr(Z)(*) in the (S(3)Tyr(Z)(*))' is slightly modified; (ii) the split EPR signal
      arising from Tyr(Z)(*) in the (S(2)Tyr(Z)(*))' state induced by near-infrared
      illumination at 4.2 K of the S(3)Tyr(Z) state is significantly modified; and
      (iii) the slow phases of P(680)(+) reduction by Tyr(Z) are slowed down from the
      hundreds of MUs time range to the ms time range, whereas both the S(1)Tyr(Z)(*) 
      > S(2)Tyr(Z) and the S(3)Tyr(Z)(*) -> S(0)Tyr(Z) + O(2) transition kinetics
      remained similar to those in PsbA(1/3)-PSII. These results show that the geometry
      of the Tyr(Z) phenol and its environment, likely the Tyr-O...H...Nepsilon-His
      bonding, are modified in PsbA2-PSII when compared with PsbA(1/3)-PSII. They also
      point to the dynamics of the proton-coupled electron transfer processes
      associated with the oxidation of Tyr(Z) being affected. From sequence comparison,
      we propose that the C144P and P173M substitutions in PsbA2-PSII versus PsbA(1/3)
      PSII, respectively located upstream of the alpha-helix bearing Tyr(Z) and between
      the two alpha-helices bearing Tyr(Z) and its hydrogen-bonded partner, His-190,
      are responsible for these changes.

PMID- 22362777
TI  - Mouse betaine-homocysteine S-methyltransferase deficiency reduces body fat via
      increasing energy expenditure and impairing lipid synthesis and enhancing glucose
      oxidation in white adipose tissue.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) catalyzes the synthesis of
      methionine from homocysteine. In our initial report, we observed a reduced body
      weight in Bhmt(-/-) mice. We initiated this study to investigate the potential
      role of BHMT in energy metabolism. Compared with the controls (Bhmt(+/+)), Bhmt(
      /-) mice had less fat mass, smaller adipocytes, and better glucose and insulin
      sensitivities. Compared with the controls, Bhmt(-/-) mice had increased energy
      expenditure, with no changes in food intake, fat uptake or absorption, or in
      locomotor activity. The reduced adiposity in Bhmt(-/-) mice was not due to
      hyperthermogenesis. Bhmt(-/-) mice failed to maintain a normal body temperature
      upon cold exposure because of limited fuel supplies. In vivo and ex vivo tests
      showed that Bhmt(-/-) mice had normal lipolytic function. The rate of (14)C
      labeled fatty acid incorporated into [(14)C]triacylglycerol was the same in
      Bhmt(+/+) and Bhmt(-/-) gonadal fat depots (GWAT), but it was 62% lower in Bhmt(
      /-) inguinal fat depots (IWAT) compared with that of Bhmt(+/+) mice. The rate of
      (14)C-labeled fatty acid oxidation was the same in both GWAT and IWAT from
      Bhmt(+/+) and Bhmt(-/-) mice. At basal level, Bhmt(-/-) GWAT had the same
      [(14)C]glucose oxidation as did the controls. When stimulated with insulin, Bhmt(
      /-) GWAT oxidized 2.4-fold more glucose than did the controls. Compared with the
      controls, the rate of [(14)C]glucose oxidation was 2.4- and 1.8-fold higher,
      respectively, in Bhmt(-/-) IWAT without or with insulin stimulus. Our results
      show for the first time a role for BHMT in energy homeostasis.

PMID- 22362778
TI  - ATM protein physically and functionally interacts with proliferating cell nuclear
      antigen to regulate DNA synthesis.
AB  - Ataxia telangiectasia (A-T) is a pleiotropic disease, with a characteristic
      hypersensitivity to ionizing radiation that is caused by biallelic mutations in A
      T mutated (ATM), a gene encoding a protein kinase critical for the induction of
      cellular responses to DNA damage, particularly to DNA double strand breaks. A
      long known characteristic of A-T cells is their ability to synthesize DNA even in
      the presence of ionizing radiation-induced DNA damage, a phenomenon termed
      radioresistant DNA synthesis. We previously reported that ATM kinase inhibition,
      but not ATM protein disruption, blocks sister chromatid exchange following DNA
      damage. We now show that ATM kinase inhibition, but not ATM protein disruption,
      also inhibits DNA synthesis. Investigating a potential physical interaction of
      ATM with the DNA replication machinery, we found that ATM co-precipitates with
      proliferating cell nuclear antigen (PCNA) from cellular extracts. Using
      bacterially purified ATM truncation mutants and in vitro translated PCNA, we
      showed that the interaction is direct and mediated by the C terminus of ATM.
      Indeed, a 20-amino acid region close to the kinase domain is sufficient for
      strong binding to PCNA. This binding is specific to ATM, because the homologous
      regions of other PIKK members, including the closely related kinase A-T and Rad3
      related (ATR), did not bind PCNA. ATM was found to bind two regions in PCNA. To
      examine the functional significance of the interaction between ATM and PCNA, we
      tested the ability of ATM to stimulate DNA synthesis by DNA polymerase delta,
      which is implicated in both DNA replication and DNA repair processes. ATM was
      observed to stimulate DNA polymerase activity in a PCNA-dependent manner.

PMID- 22362779
TI  - DNA lesion alters global conformational dynamics of Y-family DNA polymerase
      during catalysis.
AB  - A major product of oxidative damage to DNA, 8-oxo-7,8-dihydro-2'-deoxyguanine (8
      oxoG), can lead to genomic mutations if it is bypassed unfaithfully by DNA
      polymerases in vivo. However, our pre-steady-state kinetic studies show that DNA
      polymerase IV (Dpo4), a prototype Y-family enzyme from Sulfolobus solfataricus,
      can bypass 8-oxoG both efficiently and faithfully. For the first time, our
      stopped-flow FRET studies revealed that a DNA polymerase altered its synchronized
      global conformational dynamics in response to a DNA lesion. Relative to
      nucleotide incorporation into undamaged DNA, three of the four domains of Dpo4
      undertook different conformational transitions during 8-oxoG bypass and the
      subsequent extension step. Moreover, the rapid translocation of Dpo4 along DNA
      induced by nucleotide binding was significantly hindered by the interactions
      between the embedded 8-oxoG and Dpo4 during the extension step. These results
      unprecedentedly demonstrate that a Y-family DNA polymerase employs different
      global conformational dynamics when replicating undamaged and damaged DNA.

PMID- 22362780
TI  - Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ)
      fidelity at damaged ends.
AB  - Nonhomologous end joining (NHEJ) is essential for efficient repair of chromosome
      breaks. However, the NHEJ ligation step is often obstructed by break-associated
      nucleotide damage, including base loss (abasic site or 5'-dRP/AP sites). Ku, a 5'
      dRP/AP lyase, can excise such damage at ends in preparation for the ligation
      step. We show here that this activity is greatest if the abasic site is within a
      short 5' overhang, when this activity is necessary and sufficient to prepare such
      termini for ligation. In contrast, Ku is less active near 3' strand termini,
      where excision would leave a ligation-blocking alpha,beta-unsaturated aldehyde.
      The Ku AP lyase activity is also strongly suppressed by as little as two paired
      bases 5' of the abasic site. Importantly, in vitro end joining experiments show
      that abasic sites significantly embedded in double-stranded DNA do not block the
      NHEJ ligation step. Suppression of the excision activity of Ku in this context
      therefore is not essential for ligation and further helps NHEJ retain terminal
      sequence in junctions. We show that the DNA between the 5' terminus and the
      abasic site can also be retained in junctions formed by cellular NHEJ, indicating
      that these sites are at least partly resistant to other abasic site-cleaving
      activities as well. High levels of the 5'-dRP/AP lyase activity of Ku are thus
      restricted to substrates where excision of an abasic site is required for
      ligation, a degree of specificity that promotes more accurate joining.

PMID- 22362781
TI  - Acetyl-CoA carboxylase 2-/- mutant mice are protected against fatty liver under
      high-fat, high-carbohydrate dietary and de novo lipogenic conditions.
AB  - Hepatic fat accumulation resulting from increased de novo fatty acid synthesis
      leads to hepatic steatosis and hepatic insulin resistance. We have shown
      previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high
      fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet
      induced obesity and maintained whole body and hepatic insulin sensitivity. To
      determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied
      the regulation of the enzymes involved in the lipogenic pathway under Western
      HFHC dietary and de novo lipogenic conditions. After completing the HFHC regimen,
      Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal
      fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and
      higher hepatic cholesterol than wild-type mice. Significant up-regulation of
      lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) protein were found in Acc2(-/-) mutant mice under de
      novo lipogenic conditions. The increase in lipogenic enzyme levels was
      accompanied by up-regulation of the transcription factors, sterol regulatory
      element-binding proteins 1 and 2, and carbohydrate response element-binding
      protein. In contrast, hepatic levels of the PPAR-gamma and PPAR-alpha proteins
      were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet. When
      compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a
      similar level of AKT but with a significant increase in pAKT. Hence, deleting
      ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite
      increased de novo lipogenesis and dietary conditions known to induce obesity and
      diabetes.

PMID- 22362782
TI  - Autophagosomal membrane serves as platform for intracellular death-inducing
      signaling complex (iDISC)-mediated caspase-8 activation and apoptosis.
AB  - Autophagy and apoptosis are two evolutionarily conserved processes that regulate
      cell fate in response to cytotoxic stress. However, the functional relationship
      between these two processes remains far from clear. Here, we demonstrate an
      autophagy-dependent mechanism of caspase-8 activation and initiation of the
      apoptotic cascade in response to SKI-I, a pan-sphingosine kinase inhibitor, and
      bortezomib, a proteasome inhibitor. Autophagy is induced concomitantly with
      caspase-8 activation, which is responsible for initiation of the caspase cascade
      and the mitochondrial amplification loop that is required for full execution of
      apoptosis. Inhibition of autophagosome formation by depletion of Atg5 or Atg3
      results in a marked suppression of caspase-8 activation and apoptosis. Although
      caspase-8 self-association depends on p62/SQSTM1, its self-processing requires
      the autophagosomal membrane. Caspase-8 forms a complex with Atg5 and colocalizes
      with LC3 and p62. Moreover, FADD, an adaptor protein for caspase-8 activation,
      associates with Atg5 on Atg16L- and LC3-positive autophagosomal membranes and
      loss of FADD suppresses cell death. Taken together, these results indicate that
      the autophagosomal membrane serves as a platform for an intracellular death
      inducing signaling complex (iDISC) that recruits self-associated caspase-8 to
      initiate the caspase-8/-3 cascade.

PMID- 22362784
TI  - Urinary albumin to protein ratio: more of the same or making a difference?

PMID- 22362783
TI  - Human anti-prion antibodies block prion peptide fibril formation and
      neurotoxicity.
AB  - Prion diseases are a group of rare, fatal neurodegenerative disorders associated
      with a conformational transformation of the cellular prion protein (PrP(C)) into
      a self-replicating and proteinase K-resistant conformer, termed scrapie PrP
      (PrP(Sc)). Aggregates of PrP(Sc) deposited around neurons lead to
      neuropathological alterations. Currently, there is no effective treatment for
      these fatal illnesses; thus, the development of an effective therapy is a
      priority. PrP peptide-based ELISA assay methods were developed for detection and
      immunoaffinity chromatography capture was developed for purification of naturally
      occurring PrP peptide autoantibodies present in human CSF, individual donor
      serum, and commercial preparations of pooled intravenous immunoglobulin (IVIg).
      The ratio of anti-PrP autoantibodies (PrP-AA) to total IgG was ~1:1200. The
      binding epitope of purified PrP-AA was mapped to an N-terminal region comprising
      the PrP amino acid sequence KTNMK. Purified PrP-AA potently blocked fibril
      formation by a toxic 21-amino acid fragment of the PrP peptide containing the
      amino acid alanine to valine substitution corresponding to position 117 of the
      full-length peptide (A117V). Furthermore, PrP-AA attenuated the neurotoxicity of
      PrP(A117V) and wild-type peptides in rat cerebellar granule neuron (CGN)
      cultures. In contrast, IgG preparations depleted of PrP-AA had little effect on
      PrP fibril formation or PrP neurotoxicity. The specificity of PrP-AA was
      demonstrated by immunoprecipitating PrP protein in brain tissues of transgenic
      mice expressing the human PrP(A117V) epitope and Sc237 hamster. Based on these
      intriguing findings, it is suggested that human PrP-AA may be useful for
      interfering with the pathogenic effects of pathogenic prion proteins and, thereby
      has the potential to be an effective means for preventing or attenuating human
      prion disease progression.

PMID- 22362785
TI  - Development and validation of the Consumer Quality index instrument to measure
      the experience and priority of chronic dialysis patients.
AB  - BACKGROUND: Patient experience is an established indicator of quality of care.
      Validated tools that measure both experiences and priorities are lacking for
      chronic dialysis care, hampering identification of negative experiences that
      patients actually rate important. METHODS: We developed two Consumer Quality (CQ)
      index questionnaires, one for in-centre haemodialysis (CHD) and the other for
      peritoneal dialysis and home haemodialysis (PHHD) care. The instruments were
      validated using exploratory factor analyses, reliability analysis of identified
      scales and assessing the association between reliable scales and global ratings.
      We investigated opportunities for improvement by combining suboptimal experience
      with patient priority. RESULTS: Sixteen dialysis centres participated in our
      study. The pilot CQ index for CHD care consisted of 71 questions. Based on data
      of 592 respondents, we identified 42 core experience items in 10 scales with
      Cronbach's alpha ranging from 0.38 to 0.88; five were reliable (alpha >= 0.70).
      The instrument identified information on centres' fire procedures as the aspect
      of care exhibiting the biggest opportunity for improvement. The pilot CQ index
      PHHD comprised 56 questions. The response of 248 patients yielded 31 core
      experience items in nine scales with Cronbach's alpha ranging between 0.53 and
      0.85; six were reliable. Information on kidney transplantation during pre
      dialysis showed most room for improvement. However, for both types of care,
      opportunities for improvement were mostly limited. CONCLUSIONS: The CQ index
      reliably and validly captures dialysis patient experience. Overall, most care
      aspects showed limited room for improvement, mainly because patients
      participating in our study rated their experience to be optimal. To evaluate
      items with high priority, but with which relatively few patients have experience,
      more qualitative instruments should be considered.

PMID- 22362786
TI  - Disease severity score could not predict the outcomes in peritoneal dialysis
      associated peritonitis.
AB  - BACKGROUND: We aim to explore if disease severity score (DSS) at onset is
      associated with dialysate white cell counts, the severity of causative organisms
      and the risk for treatment failure of peritoneal dialysis (PD)-associated
      peritonitis in an adult PD cohort. METHODS: Our prospective cohort study recorded
      all peritonitis episodes between 2008 and 2010. The DSS, demographic data and
      clinical characteristics were recorded at the onset of peritonitis. The dialysate
      cells were counted at regular intervals and organism culture were examined too.
      Treatment failure of peritonitis was defined as peritonitis-associated death and
      transfer to haemodialysis. RESULTS: A total of 219 episodes of peritonitis in 146
      PD patients were recorded, 21.9% of which resulted in treatment failure. There
      were no significant differences in dialysate white cell counts on the fifth and
      seventh day and the distribution of causative organism between groups with varied
      DSS level. DSS could not predict treatment failure including peritonitis-related
      death and transfer to haemodialysis after adjusting for age, gender, diabetes,
      dialysis duration, dialysate white cell count on the third day, the presence of
      Staphylococcus aureus, gram-negative organisms and polymicrobial organisms.
      CONCLUSION: Our study demonstrated that DSS at onset was not associated with
      prolonged elevation of dialysate white cell counts, severity of causative
      organisms and outcome of peritonitis episodes in adult PD patients.

PMID- 22362787
TI  - Light chain cast nephropathy in Waldenstrom's macroglobulinaemia.

PMID- 22362789
TI  - Identification of bacteria recovered from animals using the 16S ribosomal RNA
      gene with pyrosequencing and Sanger sequencing.
AB  - Bacterial identification using genetic sequencing is fast becoming a confirmatory
      tool for microbiologists. Its application in veterinary diagnostic laboratories
      is still growing. In addition to availability of Sanger sequencing,
      pyrosequencing has recently emerged as a unique method for short-read DNA
      sequencing for bacterial identifications. Its ease of use makes it possible to
      diagnose infections rapidly at a low cost even in smaller laboratories. In the
      current study, pyrosequencing was compared with Sanger sequencing for
      identification of the bacterial organisms. Fifty-four bacterial isolates spanning
      23 different bacterial families encountered in veterinary diagnostic microbiology
      laboratories were sequenced using 16S ribosomal RNA gene with pyrosequencing and
      Sanger sequencing. Pyrosequencing was able to identify 80% of isolates to the
      genus level, and 43% isolates to the species level. Sanger sequencing with
      approximately 500 bp performed better for both genus (100%) and species (87%)
      identification. Use of different sequence databases to identify bacteria isolated
      from animals showed relative importance of public databases compared to a
      validated commercial library. A time and limited cost comparison between
      pyrosequencing and genetic sequencing of 500 bp showed pyrosequencing was not
      only faster but also comparable in cost, making it a viable alternative for use
      in classifying bacteria isolated from animals.

PMID- 22362788
TI  - Diagnosis of Parelaphostrongylus spp. infection as a cause of meningomyelitis in
      calves.
AB  - Migration of Parelaphostrongylus spp. has been documented to cause central
      nervous system damage in a number of aberrant host species but appears to be
      uncommon in cattle. The current report describes the clinical and laboratory
      findings, antemortem and definitive diagnosis, and response to treatment of
      Parelaphostrongylus spp. infection in five 3-7- month-old Limousin calves from 2
      farms. All calves had signs of acute (n = 2) and chronic (n = 3) progressive
      spinal cord dysfunction. Cerebrospinal fluid analysis revealed a marked
      eosinophilic (acute cases) or lymphocytic (chronic cases) pleocytosis and
      elevated protein in all calves. A necropsy and histopathologic evaluation was
      performed on 2 euthanized calves, and histopathology revealed lymphoplasmacytic
      and eosinophilic meningomyelitis with multiple intradural and intramedullary
      expansile hyperplastic lymphoid nodules containing germinal centers and nematode
      fragments. DNA sequencing was performed on nested polymerase chain reaction
      products amplified with parasite-specific primers obtained from formalin-fixed
      and frozen spinal cord; PCR products from these 2 calves were 100% identical to
      Parelaphostrongylus species on DNA sequencing, confirming the diagnosis.
      Surviving calves rapidly improved following treatment with anthelmintics and
      corticosteroids. This case series identified Parelaphostrongylus spp. (likely P.
      tenuis) as a cause of spinal cord disease in calves and highlights the need for
      vigilance against aberrant parasite migration in calves grazing wet, snail
      infested pastures. Cerebrospinal fluid eosinophilia is useful for supporting an
      antemortem diagnosis of Parelaphostrongylus in calves with acute neurologic
      disease; however, a lymphocytosis is observed in chronic or treated cases.

PMID- 22362790
TI  - Comparing citrated native, kaolin-activated, and tissue factor-activated samples
      and determining intraindividual variability for feline thromboelastography.
AB  - Thromboelastography (TEG) is a point-of-care whole blood test of hemostasis.
      While TEG is becoming more widely used in veterinary medicine, few studies
      describe the use of TEG in cats. The objectives of the current study were to: 1)
      document the range of TEG variables produced in healthy cats using 3 sample types
      (citrated native, kaolin-activated, and tissue factor-activated), and 2)
      determine if there was a significant difference between 2 separate samples
      obtained from individual healthy cats on the same day. Jugular venipuncture was
      performed in 20 cats, and citrated blood collected for TEG. TEG analysis was
      performed on citrated native, kaolin-activated, and tissue factor-activated blood
      for each sample. Two hours later, the procedure was repeated from the opposite
      jugular vein, yielding a total of 120 analyses. Reaction time (R), alpha angle
      (alpha), kappa value (kappa), and maximum amplitude (MA) were recorded from each
      tracing. No significant differences were found between TEG tracings from the
      first and second venipuncture samples. Significant differences were found between
      sample types for R, alpha, kappa, and MA. Means for citrated native/kaolin
      activated/tissue factor-activated methods were R = 4.1/3.7/0.6 min; kappa =
      2.5/1.8/2.2 min; alpha = 59.9/65.1/70.4 degrees; MA = 47.4/49.9/44.7 mm. A
      limitation of this study was the small number of cats used. Thromboelastography
      analysis may be a suitable method of evaluating hemostasis in cats.

PMID- 22362791
TI  - Variation in daily shedding patterns of Staphylococcus aureus in naturally
      occurring intramammary infections.
AB  - The goal of the current prospective field study was to examine the shedding
      patterns of naturally occurring Staphylococcus aureus intramammary infections and
      the association of pulsed field gel electrophoresis pulsotype with shedding. Milk
      samples from 5 multiparous and 2 primiparous cows identified with S. aureus
      intramammary infections were collected for 21 consecutive days, 3 times
      throughout the lactation (63 days total). Cyclicity of each quarter was evaluated
      using a locally weighted regression. Pulsed field gel electrophoresis was used
      for genotypic cluster comparisons to evaluate the association of strain type and
      shedding patterns. Although the amount of shedding varied greatly, 97.5% of the
      samples were culture positive. There were notable differences in S. aureus
      shedding patterns among cows as well as within cows; however, no consistent
      cyclic pattern was identified. Quarters infected with S. aureus isolates grouped
      in genotypic cluster 1 appeared to shed at consistently higher levels with a
      median cfu/0.01 ml of 154 (ln[cfu] = 5.0). In comparing ln(cfu)/0.01 ml between
      genotypic clusters over the first 21-day sample period, accounting for the effect
      of sample day, samples collected from quarters infected with S. aureus in
      genotypic cluster 1 had a 1.5 times greater ln(cfu) than those collected from
      quarters infected with strains in genotypic cluster 2. The ability to detect S.
      aureus from day to day was very consistent. The current study examining naturally
      occurring intramammary infections would support the conclusions of other studies
      suggesting that a single quarter sample would be adequate in determining S.
      aureus intramammary infections status.

PMID- 22362792
TI  - Mycoplasmas in Australian fur seals (Arctocephalus pusillus doriferus):
      identification and association with abortion.
AB  - Bacteria from the genus Mycoplasma are common inhabitants of the respiratory,
      gastrointestinal, and genital tracts of mammals. The understanding of the
      pathological significance of mycoplasmas in seals is poor, as few studies have
      utilized the specific culture techniques required to isolate these bacteria. The
      current study surveyed for the Mycoplasma species present in Australian fur seals
      (Arctocephalus pusillus doriferus) and investigated the association between
      infection and pathology. Mycoplasmas were found in the nasal cavities of 55/80
      (69%) of apparently healthy individuals. Isolates from 18 individuals were
      investigated through 16S ribosomal RNA sequencing, and 3 species were identified:
      M. zalophi, M. phocae, and Mycoplasma sp. (GenBank no. EU714238.1), all of which
      had previously been isolated from Northern Hemisphere pinnipeds. In addition,
      mycoplasmas were isolated from the lungs of 4 out of 16 juveniles and 1 out of 5
      adults sampled at necropsy. Isolates obtained were M. zalophi, Mycoplasma sp.
      EU714238.1, and M. phocicerebrale, but infection was not associated with lung
      pathology in these age classes. Inflammatory disease processes of the heart
      and/or lungs were present in 12 out of 32 (38%) aborted fetuses on microscopic
      examination. Predominant findings were interstitial pneumonia, pericarditis, and
      myocarditis. Mycoplasma phocicerebrale was isolated from the thymus of an aborted
      fetus, and 3 out of 11 (27%) fetuses with inflammatory heart or lung lesions were
      PCR-positive for Mycoplasma. In conclusion, several species of Mycoplasma are
      part of the normal flora of the nasal cavity of Australian fur seals, and some
      mycoplasmas may be associated with abortion in this species of seal.

PMID- 22362793
TI  - Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie
      dogs and high frequency of the mutant allele in Japan.
AB  - Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited
      lysosomal storage diseases that primarily affect neuronal cells. Such diseases
      share certain clinical and pathologic features in human beings and animals.
      Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in
      Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense
      mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel
      rapid genotyping assays including polymerase chain reaction (PCR)-restriction
      fragment length polymorphism, PCR primer-induced restriction analysis,
      mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder
      probes, were developed. The utility of microchip electrophoresis was also
      evaluated. Furthermore, a genotyping survey was carried out in a population of
      Border Collies in Japan using these assays to determine the current allele
      frequency in Japan, providing information to control and prevent this disease in
      the next stage. All assays developed in the current study are available to
      discriminate these genotypes, and microchip electrophoresis showed a timesaving
      advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the
      most suitable for large-scale examination because of its high throughput. The
      genotyping survey demonstrated that the carrier frequency was 8.1%. This finding
      suggested that the mutant allele frequency of NCL in Border Collies is high
      enough in Japan that measures to control and prevent the disease would be
      warranted. The genotyping assays developed in the present study could contribute
      to the prevention of NCL in Border Collies.

PMID- 22362794
TI  - Species characterization and minimum inhibitory concentration patterns of
      Brachyspira species isolates from swine with clinical disease.
AB  - Typhlocolitis and dysentery due to Brachyspira hyodysenteriae infection represent
      an economically important disease syndrome in growing pigs. Largely disappearing
      from U.S. swine herds in the late 1990 s and early 2000s, Brachyspira-associated
      disease and bacterial isolation from swine with clinical disease has increased in
      the last several years, and non-B. hyodysenteriae isolates are commonly
      identified. Antimicrobial resistance has been demonstrated in Brachyspira spp.
      isolates from Europe and Asia, and may be the reason for the resurgence in U.S.
      herds. Seventy-nine clinical isolates identified at the Iowa State University
      Veterinary Diagnostic Lab were tested with multiple polymerase chain reaction
      assays to establish species identity, and evaluated for minimum inhibitory
      concentrations (MICs) using an agar dilution method against lincomycin,
      gentamicin, valnemulin, tiamulin, salinomycin, and carbadox. Only 38.0% of
      isolates could be confirmed as the known pathogens B. hyodysenteriae (30.4%) or
      Brachyspira pilosicoli (7.6%). Twenty of the 79 isolates (25.3%) were identified
      as Brachyspira murdochii, and 13.9% could not be identified to species. The MIC
      values were consistently high against lincomycin and moderately high against
      gentamicin. The remaining antimicrobials had MICs that were at the low end of the
      test ranges. Brachyspira murdochii and Brachyspira spp. had significantly greater
      MIC values against several of these drugs than other Brachyspira spp. examined.
      The increased incidence of these less definitively characterized Brachyspira
      species with increased MIC values to commonly prescribed antimicrobials may, at
      least in part, explain the increased prevalence and severity of this disease
      complex in recent years. Further research is necessary to understand these
      changes.

PMID- 22362795
TI  - Escherichia coli from clinical mastitis: serotypes and virulence factors.
AB  - In the current study, the virulence factors in Escherichia coli isolates from
      bovine mastitis were investigated, and the connection between these factors and
      infection was evaluated using phenotypic and genotypic analyses. Twenty-seven E.
      coli isolates were analyzed, and 2 were shown to produce verotoxin. All isolates
      had the ability to produce biofilms, although at different levels. One isolate
      was found to be sensitive to the bactericidal activity of bovine serum, 11 were
      intermediate, and 15 were resistant. Some isolates showed resistance to
      trimethoprim sulfa (9) and ampicillin (4), intermediate resistance to neomycin
      (1) and trimethoprim sulfa (5), and simultaneous resistance to ampicillin and
      trimethoprim sulfa (4). The fimH gene was found in all isolates and was
      associated with other virulence markers: pap (1), stb (8), cs31a (3), stb and vt2
      (2), cs31a and stb (3), east1 and kps (1), stb and east1 (1), cs31a and east1
      (1), and cs31a, stb, pap, and iucD (1). Serogroups were determined for 3
      isolates: O93:H4, O83:H19, and O15:H11. Phylogenetic analysis showed that 23
      isolates belonged to group A and 4 belonged to B1. The findings revealed that
      these E. coli isolates are opportunistic pathogens with different virulence
      factors. The results indicate that the pathogenicity route of E. coli in bovine
      mastitis is not a consequence of 1 specific virulence factor.

PMID- 22362796
TI  - Quantitative duplex TaqMan real-time polymerase chain reaction for the assessment
      of the etiologic agent of epizootic bovine abortion.
AB  - Epizootic bovine abortion (EBA), also commonly known as "foothill abortion," is a
      late-term abortion primarily in beef cattle with significant economic impacts in
      California, Nevada, and Oregon. The causative agent is a novel
      deltaproteobacterium (aoEBA) closely related to the order Myxococcales and
      vectored by the soft-shelled tick Ornithodoros coriaceus. Historically, diagnosis
      has relied upon the pathologic examination of the fetus and the presence of
      elevated fetal serum immunoglobulins. Identification of the etiologic agent, a
      unique deltaproteobacterium, permitted the development of a quantitative duplex
      real-time polymerase chain reaction (qPCR) using a unique 90-bp sequence of aoEBA
      16S ribosomal RNA gene in conjunction with an 88-bp sequence of the bovine beta
      actin gene. Reaction efficiencies were 100.9% for the 16S aoEBA gene and 93.1%
      for the bovine beta-actin gene. Application of the duplex TaqMan to a set of
      aoEBA-infected fetal bovine necropsy tissues demonstrated the assay to be robust
      in quantitatively identifying the aoEBA bacteria and establishing host-tissue
      pathogen load. Consistent with previously reported immunohistochemical data,
      organized lymphoid tissue generally carried the heaviest bacterial load as
      compared to non-lymphoid tissue. The newly developed duplex TaqMan assay will
      facilitate diagnosis in difficult cases and provide an invaluable tool for
      delineating the pathogenesis of EBA.

PMID- 22362797
TI  - Comparative evaluation of a competitive polymerase chain reaction (PCR) and a
      SYBR Green-based real-time PCR to quantify Porcine circovirus-2 DNA in swine
      tissue samples.
AB  - Porcine circovirus-2 (PCV-2) is considered the major etiological agent of post
      weaning multisystemic wasting syndrome (PMWS) in pigs. The clinical
      manifestations of the disease are correlated with moderate to high amounts of PCV
      2 DNA in biological samples of affected pigs. A threshold of 10(7) DNA copies/ml
      is suggested as the trigger factor for symptoms. A comparative study was
      conducted to determine which quantitative method would be more suitable to
      estimate the PCV-2 DNA load. Two polymerase chain reaction (PCR) assays were
      developed: a competitive PCR (cPCR) and a SYBR Green-based real-time PCR. The
      assays were compared for their capacity to detect PCV-2 in DNA samples extracted
      from liver, lung, spleen, mesenteric lymph nodes, and kidney of PMWS-affected (n
      = 23) or non-PMWS-affected pigs (n = 9). Both assays could successfully quantify
      PCV-2 DNA in all tissue samples and were able to detect significant differences
      between the numbers of PCV-2 DNA copies found in tissues of PMWS-affected and non
      PMWS-affected pigs (>= 10(2.5)). The highest mean viral loads were detected by
      the SYBR Green real-time PCR, up to 10(7.0 +/- 1.5) copies/100 ng of total DNA
      sample, while the cPCR detected up to 10(4.8 +/- 1.5). A mean difference of
      10(1.8) was found between the amounts of PCV-2 DNA detected, using the SYBR Green
      real-time PCR and the cPCR, suggesting that the viral load threshold for PMWS
      should be determined for each particular assay.

PMID- 22362798
TI  - Evaluation of the automated hematology analyzer Sysmex XT-2000iVTM compared to
      the ADVIA(r) 2120 for its use in dogs, cats, and horses: Part I--precision,
      linearity, and accuracy of complete blood cell count.
AB  - The automated laser-based hematology analyzer Sysmex XT-2000iVTM providing a
      complete blood cell count (CBC) and 5-part differential has been introduced in
      large veterinary laboratories. The aim of the current study was to determine
      precision, linearity, and accuracy of the Sysmex analyzer. Reference method for
      the accuracy study was the laser-based hematology analyzer ADVIA(r) 2120. For
      evaluation of accuracy, consecutive fresh blood samples from healthy and diseased
      cats (n = 216), dogs (n = 314), and horses (n = 174) were included. A low intra
      assay coefficient of variation (CV) of approximately 1% was seen for the CBC
      except platelet count (PLT). An intra-assay CV ranging between 2% and 5.5% was
      evident for the differential count except for feline and equine monocytes (7.7%)
      and horse eosinophils (15.7%). Linearity was excellent for white blood cell count
      (WBC), hematocrit value, red blood cell count (RBC), and PLT. For all evaluated
      species, agreement was excellent for WBC and RBC, with Spearman rank correlation
      coefficients (r(s)) ranging from >0.99 to 0.98. Hematocrit value correlated
      excellently in cats and dogs, whereas for horses, a good correlation was evident.
      A good correlation between both analyzers was seen in feline and equine PLT (r(s)
      = 0.89 and 0.92, respectively), whereas correlation was excellent for dogs (r(s)
      = 0.93). Biases were close to 0 except for mean corpuscular hemoglobin
      concentration (4.11 to -7.25 mmol/l) and canine PLT (57 * 10(9)/l). Overall, the
      performance of the Sysmex analyzer was excellent and compared favorably with the
      ADVIA analyzer.

PMID- 22362799
TI  - Serological cross-reactivity between Anaplasma marginale and an Ehrlichia species
      in naturally and experimentally infected cattle.
AB  - Seroconversion and cross-reactivity in cattle infected with Anaplasma marginale
      or a recently described Ehrlichia species (BOV2010 from British Columbia, Canada)
      were investigated. The study used 76 samples from 20 animals, a commercially
      available competitive enzyme-linked immunosorbent assay (cELISA) for bovine
      anaplasmosis, and an indirect fluorescent antibody test (IFAT). Blood smear
      examination and/or polymerase chain reaction assay were performed to confirm or
      rule out the presence of Anaplasma or Ehrlichia. Samples comprised 3 groups.
      Group 1 consisted of 24 samples from 9 cattle naturally infected with Ehrlichia
      sp. BOV2010. Group 2 had 13 samples from 3 A. marginale-infected cattle from
      Manitoba, Canada. Group 3 had 39 samples, consisting of 26 from 5 calves
      experimentally infected with Ehrlichia sp. BOV2010, 10 from 2 calves
      experimentally infected with A. marginale from cattle (Manitoba) or bison
      (Saskatchewan), and 3 from an uninfected calf. All samples from cattle naturally
      or experimentally infected with Ehrlichia sp. BOV2010 or A. marginale were
      seropositive for A. marginale by both cELISA and IFAT, except 3 calves euthanized
      at 28 and 33 days post-inoculation (DPI) that did not seroconvert. Antibodies
      were detected in 2 experimental animals inoculated with Ehrlichia sp. BOV2010, as
      early as 28 and 33 DPI by the cELISA and IFAT, respectively, and by 42 DPI for
      both tests. The current study demonstrates that the specificity of the
      recombinant major surface protein 5 (MSP5) antigen is not restricted to Anaplasma
      spp., which reduces the utility of the test for serological diagnosis of bovine
      anaplasmosis in regions where Ehrlichia sp. BOV2010-infected cattle might exist.

PMID- 22362800
TI  - Effects of DNA extraction method on Porcine circovirus-2 real-time polymerase
      chain reaction quantification in swine lymph node samples.
AB  - Quantitative real-time polymerase chain reaction (PCR) has become an important
      tool for Porcine circovirus-2 (PCV-2) research and diagnosis. However,
      significant differences in detection limit and quantification data, among
      laboratories and quantitative real-time PCR methods, have been demonstrated. New
      efforts are required for providing more accurate and comparable results. The
      current study is an evaluation of the effects of DNA extraction procedures on PCV
      2 quantification in lymph node samples. Differences, greater than 1 log(10)
      copies/g, were shown among PCV-2 loads detected after different extraction
      procedures. The work highlighted the critical role of the DNA extraction method
      in PCV-2 quantification by quantitative real-time PCR. This important aspect
      should be evaluated when comparing data from different laboratories or different
      studies. The PCV-2 quantification data should not be considered comparable before
      demonstrating the equivalence of the DNA extraction methods performed.

PMID- 22362801
TI  - Evaluation of a rapid immunochromatographic test strip for detection of Rabies
      virus in dog saliva samples.
AB  - An immunochromatographic test strip for Rabies virus was evaluated with dog
      saliva samples. The test was initially validated against 237 dogs of known
      infection status, and then evaluated in the field with 1,290 live dogs. By
      validation of paired saliva-brain specimens obtained from dogs at necropsy, the
      saliva strip test was 94.4% specific and 93.0% sensitive when compared to the
      gold standard fluorescent antibody test (FAT) on brain smears. The sensitivity
      and specificity of a nested polymerase chain reaction (nPCR) assay using saliva
      were 100% compared to the FAT results. The performance of strip test with field
      saliva samples from street dogs had a specificity of 98.7% in comparison to nPCR
      as the reference method. As the strip test kit can potentially be used outside
      the laboratory and be applicable as an on-site testing assay, it represents a
      powerful screening tool for epidemiological surveys and disease control. The test
      could be useful for the surveillance of rabies in dogs and, in particular, be
      used to monitor the success of rabies control programs.

PMID- 22362802
TI  - Rapid detection of GM1 ganglioside in cerebrospinal fluid in dogs with GM1
      gangliosidosis using matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry.
AB  - The concentration of GM1 (monosialotetrahexosyl ganglioside) in cerebrospinal
      fluid (CSF) is markedly increased in dogs with GM1 gangliosidosis due to GM1
      accumulation in the central nervous system and leakage to the CSF. The present
      study established a rapid and simple method for detection of accumulated GM1 in
      the CSF in dogs with GM1 gangliosidosis using matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI TOF MS) and discusses the
      usefulness of this method for the rapid diagnosis and/or high-risk screening of
      this disease in domestic animals. Cerebrospinal fluid was collected from normal
      dogs and 4- to 11-month-old Shiba dogs with GM1 gangliosidosis. The MALDI TOF MS
      analysis was carried out in combination with a special sample plate and a simple
      desalting step on the plate. Specific signs of GM1 could be detected in the
      standard GM1 solutions at concentrations of 50 nmol/l or more. The signs were
      also clearly detected in CSF (131-618 nmol/l) in affected dogs, but not in normal
      canine CSF (12 +/- 5 nmol/l, mean +/- standard deviation). The results
      demonstrated that MALDI TOF MS can detect GM1 accumulated in canine CSF even in
      the early stage of the disease. In conclusion, the rapid detection of increased
      CSF GM1 using MALDI TOF MS is a useful method for diagnosis and/or screening for
      canine GM1 gangliosidosis.

PMID- 22362803
TI  - Phenotype characterization of Staphylococcus species strains isolated from
      buffalo (Bubalus bubalis) milk.
AB  - The objective of the current study was to isolate and identify phenotypes of
      Staphylococcus spp. strains derived from buffalo (Bubalus bubalis) milk. A total
      of 548 milk samples from 137 buffalo were cultured in Columbia agar enriched with
      5% defibrinated sheep blood. Determination of the capacity of Staphylococcus
      aureus to produce enterotoxins A-D and toxic shock syndrome toxin-1 (TSST-1) was
      achieved by reverse passive latex agglutination (RPLA). Antimicrobial sensitivity
      of S. aureus strains was evaluated using the disk diffusion technique, and beta
      lactamase detection was achieved using the chromogenic test with paper discs
      impregnated with nitrocefin. From all the mammary quarters examined, 36 (10.8%)
      were positive for Staphylococcus spp., 83.3% were coagulase-negative
      staphylococcus (CNS), 11.1% were coagulase-positive staphylococcus (CPS), and
      5.6% were of CPS+CNS positive. All isolates of S. aureus produced at least 1
      toxin and 5 out of 6 isolates (83.0%) produced beta-lactamase. One hundred
      percent of S. aureus isolates were sensitive to methicillin and amoxicillin +
      clavulanic acid, and resistant to ampicillin, penicillin, and oxacillin. Analysis
      of the results obtained in the current study highlight the epidemiologic
      importance of buffalo milk regarding the production of enterotoxins and TSST-1
      and the potential risk to public health.

PMID- 22362804
TI  - Influence of prolonged formalin fixation of tissue samples on the sensitivity of
      chromogenic in situ hybridization.
AB  - Chromogenic in situ hybridization (ISH) is a commonly used tool in diagnostic
      pathology to detect pathogens in formalin-fixed, paraffin-embedded (FFPE) tissue
      sections. Prolonged formalin fixation time was identified to be a limiting factor
      for the successful detection of nucleic acid from different pathogens, most
      probably due to the cross-linking activity of formalin between RNA, DNA, and
      proteins. Therefore, in the current study, the influence of formalin fixation
      time on ISH signal intensity of 2 viral (Porcine circovirus-2 [PCV-2] and Porcine
      respiratory and reproductive virus [PRRSV]) and 2 protozoal agents
      (Cryptosporidium serpentis and Tritrichomonas sp.) was evaluated. Tissue samples
      were fixed in 7% neutral buffered formaldehyde solution, and at defined
      intervals, pieces were embedded in paraffin wax and subjected to pathogen
      specific ISH. For all 4 pathogens, the signal intensity remained comparable with
      the starting ISH signal for different periods of fixation (PCV-2: 6 weeks, PRRSV:
      23 weeks, C. serpentis: 55 weeks, Tritrichomonas sp.: 53 weeks). Thereafter, the
      signal started to decline until loss of nucleic acid detection. The influence of
      increased proteinase K concentrations for inverting the formalin-induced cross
      linking activity was examined compared with the standard protocol. With all 4
      infectious agents, a 4-fold proteinase K concentration restored the ISH signals
      to a level comparable with 1 day of fixation. In conclusion, the influence of
      prolonged formalin fixation on the intensity of detected ISH signal highly
      depends on the analyzed infectious agent and the pretreatment protocol.

PMID- 22362805
TI  - The pathology associated with visceral toxicosis of catfish.
AB  - Visceral toxicosis of catfish (VTC) syndrome was recognized in the late 1990 s
      and recently has been associated with exposure to Clostridium botulinum type E
      neurotoxin. Tentative diagnosis is based on clinical presentation and gross
      findings, and is confirmed by bioassay. In April 2009, channel catfish (Ictalurus
      punctatus) from 2 different farms presented with abnormal swimming behavior and
      mortalities. Nine fish were submitted to the Aquatic Research and Diagnostic
      Laboratory (Stoneville, Mississippi) for evaluation. Bacterial cultures from
      these fish were negative. Necropsy findings included intestinal intussusceptions,
      ascites, pale proximal intestines with engorged serosal blood vessels, splenic
      congestion, and a reticular pattern to the liver. Significant histopathologic
      findings were limited to cerebral, splenic, and hepatic congestion, splenic
      lymphoid depletion and perivascular edema, vascular dilation and edema of the
      gastrointestinal tract, and perivascular edema in the anterior and posterior
      kidneys. Intoxication from C. botulinum type E neurotoxin was suspected based on
      the clinical signs and lack of gross and microbiological evidence of an
      infectious disease process. The toxicosis was confirmed with a positive bioassay
      using serum collected from the submitted fish.

PMID- 22362806
TI  - Multiple cutaneous mast cell tumors in a pig.
AB  - Cutaneous tumors are not usually observed in pigs, and mast cell tumors, in
      particular, have been rarely described. The current report describes numerous,
      pink to red, elevated, 1-5-cm nodules in the skin of a 6-month-old slaughter pig.
      The histopathology of the nodules revealed well-demarcated, but poorly
      differentiated, populations of round cells that extended from the dermis into
      subcutaneous tissues. The presence of eosinophils and the observation, at high
      magnification, of cells with cytoplasmic metachromatic granules, after toluidine
      blue staining, confirmed the diagnosis of multiple cutaneous mast cell tumors.

PMID- 22362807
TI  - Amorimia exotropica poisoning as a presumptive cause of myocardial fibrosis in
      cattle.
AB  - The current study reports the investigation on the cause of sudden deaths
      associated with cardiac fibrosis in cattle in northern Rio Grande do Sul, Brazil.
      The exclusion of known causes of bovine cardiac fibrosis as well as the absence
      of the plants in that region whose consumption has already been linked to the
      disorder motivated this investigation. The condition, which was attributed to the
      consumption of Amorimia exotropica, affected draft oxen, most of which died
      suddenly without showing any clinical signs during usual management or work.
      Globular hearts with white foci at their cut surfaces were the main gross
      findings, which corresponded microscopically from multifocal to coalescent areas
      of myocardial fibrosis. To confirm the condition, A. exotropica from the ranches
      where cattle died from the disease was dosed to rabbits, which showed similar
      lesions to those seen in dead cattle after receiving 10 doses of 3.6 g/kg at 4
      day intervals. Electron microscopy on rabbit tissues revealed severe tumefaction
      of the cardiomyocytes associated with mitochondrial swelling, displacement, and
      rupture of the mitochondrial crests, and of the bundles of myofibrils, apart from
      large glycogen deposits within the sarcoplasm. It is suggested that mitochondrial
      changes triggered alterations that lead to cardiac fibrosis and that all of these
      changes were induced by A. exotropica cardiotoxicity.

PMID- 22362808
TI  - Sebaceous metaplasia in a canine mammary gland non-infiltrative carcinoma with
      myoepithelial component.
AB  - Sebaceous metaplasia in canine mammary tumors is a rare condition with only 1
      case documented. The current study describes a case of sebaceous metaplasia in a
      mammary gland carcinoma of an 8-year-old intact, nulliparous female Poodle dog
      with a subcutaneous tumor located in the left fifth mammary gland. The lesion
      measured 0.7 cm * 0.5 cm * 0.6 cm in diameter, was firm, circumscribed, painless,
      non-haired, and non-ulcerated, and did not adhere to deep tissues. The cut
      surface was non-lobulated, non-encapsulated, whitish to gray, and opaque.
      Histological evaluation revealed 3 different populations of cells: the first was
      composed of columnar to cuboidal malignant epithelial cells arranged in
      intraductal papillary projections, the second of myoepithelial cells associated
      with a myxoid stroma, and the third presenting sebaceous metaplasia similar to
      those previously described in both human and veterinary medicine.

PMID- 22362809
TI  - Arcanobacterium haemolyticum in a badger (Meles meles).
AB  - A 7.5-kg female European badger (Meles meles) was submitted under the United
      Kingdom Government's Wildlife Incident Investigation Scheme to the Thirsk
      Regional Laboratory of the Animal Health and Veterinary Laboratories Agency.
      Postmortem examination revealed a large, poorly encapsulated retropharyngeal
      abscess full of necrotic debris and pus. Arcanobacterium haemolyticum was
      isolated from the lymph node and confirmed by phenotypic profiling and 16S
      ribosomal RNA DNA sequencing. Workers should be aware of the potential for
      badgers to harbor zoonoses other than those more traditionally associated with
      the species.

PMID- 22362810
TI  - Outbreak of equine endometritis caused by a genotypically identical strain of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that has been recognized as a
      cause of endometritis in mares. Pulsed field gel electrophoresis was used to
      characterize and compare isolates of P. aeruginosa from an outbreak of
      endometritis and unrelated isolates collected at the same time as the outbreak.
      The restriction endonuclease digestion patterns and antimicrobial resistance
      profiles of all outbreak isolates were identical. Therefore, a single strain of
      P. aeruginosa was responsible for the cases of endometritis. The unrelated
      isolates could be distinguished from the outbreak strain using the techniques
      outlined in the present study. The results establish that this pathogen was not
      venereally transmitted between all the horses from which it was isolated, but
      rather must have been disseminated, at least initially, from a contaminated water
      source. Once the water used to clean the mares and stallions was replaced, there
      were no further reports of endometritis caused by this organism on the affected
      stud. Furthermore, the fertility of the stallions was not affected, in spite of
      persistent carriage for 1 to 2 months. The current study has shown that the use
      of pulsed field gel electrophoresis has considerable value in epidemiological
      investigations of equine urogenital tract infections with P. aeruginosa.

PMID- 22362811
TI  - Clostridium piliforme encephalitis in a weaver bird (Ploceus castaneiceps).
AB  - A juvenile Taveta golden weaver (Ploceus castaneiceps) bird housed in a zoo
      aviary developed a sudden onset of neurological signs. The bird demonstrated head
      tilt, rolling onto its back, and inability to perch. Euthanasia was elected due
      to lack of response to intensive care, and a necropsy was performed. There were
      no significant abnormal findings on gross examination. On histopathology, the
      remarkable findings were localized to the brain and consisted of multifocal
      cerebral microabscesses and rarefaction. Filamentous rod-shaped bacteria were
      present within and at the periphery of the necrotic foci, and dispersed
      throughout the neuroparenchyma and intracellularly in neurons. The bacteria were
      Gram negative, and Warthin-Starry stain demonstrated characteristic "hay
      stacking." Real-time polymerase chain reaction analysis of the brain identified
      the agent as Clostridium piliforme. An additional microscopic finding was severe
      crypt enteritis; however, the bacteria were not observed in the intestinal
      sections.

PMID- 22362812
TI  - Parasitic ventriculitis caused by Hadjelia truncata in California rock pigeons
      (Columba livia).
AB  - Severe ventriculitis and emaciation caused by the infestation of the nematode
      Hadjelia truncata occurred in meat-type breeder rock pigeons (Columba livia) in
      southern and central California. Hadjelia truncata can infest several species of
      birds, although it has only been reported as pathogenic in pigeons. The factors
      that contribute to H. truncata pathogenicity are not known. The gross and
      microscopic pathology caused by the infestation of H. truncata in the ventriculus
      of pigeons and its morphological identification are presented.

PMID- 22362813
TI  - Upfront association of carboplatin plus pemetrexed in patients with brain
      metastases of lung adenocarcinoma.
AB  - Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain
      metastases at the time of diagnosis. When surgical resection is not possible,
      whole brain radiotherapy is the standard of care, with a cerebral response rate
      of approximately 30%. We report our experience with an upfront association of
      carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m(2),
      respectively), every 3 weeks, in 30 patients presenting with newly diagnosed
      brain metastases and NSCLC. Cerebral MRIs were performed every 6-9 weeks. The
      radiologic response rates were assessed according to Response Evaluation Criteria
      in Solid Tumors. Overall survival was also determined. Twenty-six patients were
      evaluable for response, and the objective cerebral response rate (complete and
      partial response) in the intent-to-treat population was 40% (12 of 30 patients).
      Event-free survival was 31 weeks, and median overall survival was 39 weeks. The
      upfront association of carboplatin plus pemetrexed allows simultaneous treatment
      of cerebral and systemic disease in patients with NSCLC with newly diagnosed
      brain metastases and appears to be particularly interesting in terms of
      radiologic response and overall survival. Further clinical studies are warranted.

PMID- 22362815
TI  - Endothelial NADPH oxidase 2: when does it matter in atherosclerosis?

PMID- 22362814
TI  - Vascular smooth muscle cell phenotypic plasticity: focus on chromatin
      remodelling.
AB  - Differentiated vascular smooth muscle cells (SMCs) retain the capacity to modify
      their phenotype in response to inflammation or injury. This phenotypic switching
      is a crucial component of vascular disease, and is partly dependent on epigenetic
      regulation. An appreciation has been building in the literature for the essential
      role chromatin remodelling plays both in SMC lineage determination and in
      influencing changes in SMC behaviour and state. This process includes numerous
      chromatin regulatory elements and pathways such as histone acetyltransferases,
      deacetylases, and methyltransferases and other factors that act at SMC-specific
      marker sites to silence or permit access to the cellular transcriptional
      machinery and on other key regulatory elements such as myocardin and Kruppel-like
      factor 4 (KLF4). Various stimuli known to alter the SMC phenotype, such as
      transforming growth factor beta (TGF-beta), platelet-derived growth factor
      (PDGF), oxidized phospholipids, and retinoic acid, appear to act in part through
      effects upon SMC chromatin structure. In recent years, specific covalent histone
      modifications that appear to establish SMC determinacy have been identified,
      while others alter the differentiation state. In this article, we review the
      mechanisms of chromatin remodelling as it applies to the SMC phenotype.

PMID- 22362816
TI  - Regulating a uniter: control of mitofusin 2 expression.

PMID- 22362817
TI  - Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of
      atorvastatin in a mouse model of accelerated atherosclerosis.
AB  - AIMS: The aim of the present study was to assess whether the addition of a nitric
      oxide (NO)-donating moiety to atorvastatin enhances anti-inflammatory and anti
      atherogenic effects in an animal model of endothelial dysfunction, systemic
      peroxidation and inflammation, and accelerated atherosclerosis. METHODS AND
      RESULTS: Low-density lipoprotein receptor (LDLR)(-/-) mice kept on a high-fat
      diet (HFD) for 16 weeks underwent photochemical injury to the femoral artery with
      the local production of oxygen radicals. HFD markedly enhanced cholesterol,
      inflammatory biomarkers in plasma and in the femoral arterial wall, and
      atherosclerotic lesions in the aortic arch; inflammation and atherosclerosis were
      further increased by photochemically generated oxygen radicals. Treatment with
      the NO-donating atorvastatin NCX 6560 (11.7 mg/kg) was significantly more
      effective than atorvastatin (10 mg/kg) in reducing the following parameters:
      lipid-rich lesions in the aortic arch (surface covered: atorvastatin = 24 +/- 5%;
      NCX 6560 = 14.7 +/- 3.9%; P< 0.05); the production of radical oxygen species in
      the aorta (dichlorofluorescein fluorescence intensity per milligram of protein:
      atorvastatin = 2419 +/- 136.7; NCX 6560 = 1766 +/- 161.2; P< 0.05); femoral
      artery intima/media thickness (atorvastatin = 1.2 +/- 0.11; NCX 6560 = 0.3 +/-
      0.14; P< 0.05); circulating interleukin-6 (atorvastatin = 34.3 +/- 6.8 pg/mL; NCX
      6560 = 17.7 +/- 14.4 pg/mL; P< 0.05); and matrix metalloproteinase 2 in the
      arterial wall (atorvastatin = 55.2 +/- 1.9 ng/ug of proteins; NCX 6560 = 45.8 +/-
      2.6 ng/ug of proteins; P < 0.05). CONCLUSION: In conditions of severe endothelial
      dysfunction, systemic peroxidation and inflammation, and accelerated
      atherosclerosis, atorvastatin, even at high doses, displays suboptimal anti
      atherogenic and anti-inflammatory effects, while the addition of a NO-donating
      property confers enhanced anti-atherogenic and anti-inflammatory effects.

PMID- 22362818
TI  - In situ removal of the pipeline embolization device: the 'corking' and 'pseudo
      corking' techniques.
AB  - The pipeline embolization device (PED) is a revolutionary tool for the
      endovascular treatment of intracranial aneurysms by flow diversion. Treatment
      using the PED often requires considerable manipulation and customization by the
      neurointerventionalist at the time of deployment. Proper use of the PED involves
      a novel set of techniques and associated jargon, which must be learned by all
      neurointerventionalists, fellows and residents for safe treatment of patients
      with this device. In this report, the PED removal techniques referred to as
      'corking' and 'pseudo-corking' are described. Corking is used for the removal of
      a partially deployed in situ PED when the pusher wire is intact whereas 'pseudo
      corking' is used if the pusher wire is fractured or disconnected. Knowledge of
      both techniques is necessary for withdrawing the PED in situations of malposition
      or failed expansion.

PMID- 22362821
TI  - Clinical review: Disorders of water homeostasis in neurosurgical patients.
AB  - CONTEXT: Disorders of water balance are common in neurosurgical patients and
      usually manifest as hypo- or hypernatremia. They are most commonly seen after
      subarachnoid hemorrhage, traumatic brain injury, with intracranial tumors, and
      after pituitary surgery. SETTING: We reviewed the experience of endocrine
      evaluation and management of disorders of salt and water balance in a large
      cohort of inpatients attending the national neurosciences referral centre in
      Dublin, Ireland, and compared this experience with findings from other studies.
      PATIENTS: The study group included unselected neurosurgical patients admitted to
      our centre and requiring endocrine evaluation. INTERVENTIONS: We conducted
      investigations to determine the underlying mechanistic basis for disorders of
      salt and water balance in neurosurgical patients and treatment to restore normal
      metabolism. MAIN OUTCOME MEASURES: Morbidity and mortality associated with
      deranged salt and water balance were measured. RESULTS: The underlying
      pathophysiology of disordered water balance in neurosurgical patients is complex
      and varied and dictates the optimal therapeutic approach. CONCLUSIONS: A
      systematic and well-informed approach is needed to properly diagnose and manage
      disorders of salt and water balance in neurosurgical patients.

PMID- 22362820
TI  - Overexpression of 17beta-hydroxysteroid dehydrogenase type 1 increases the
      exposure of endometrial cancer to 17beta-estradiol.
AB  - CONTEXT: The local interconversions between estrone (low activity) and 17beta
      estradiol (potent compound) by 17beta-hydroxysteroid dehydrogenases (17beta-HSDs)
      can lead to high 17beta-estradiol generation in endometrial cancer (EC).
      OBJECTIVE: Examine the balance between the 17beta-HSDs reducing estrone to 17beta
      estradiol (types 1, 5, 12, and 7) and those oxidizing 17beta-estradiol to estrone
      (2, 4, and 8), in EC. PATIENTS AND METHODS: Reducing and oxidizing 17beta-HSD
      activities (HPLC) and mRNA level (RT-PCR) were assessed in normal post-menopausal
      (n = 16), peritumoral endometrium (normal tissue beside cancer, n = 13), and 58
      EC (29 grade 1, 18 grade 2, 11 grade 3). RESULTS: Grade 1 EC displayed a shifted
      estrone reduction/17beta-estradiol oxidation balance in favor of 17beta-estradiol
      compared with controls. This was more pronounced among estrogen receptor-alpha
      (ER-alpha)-positive biopsies. Type 1 17beta-HSD mRNA (HSD17B1 gene expression,
      real time PCR) and protein levels (immunohistochemistry) were higher in ER-alpha
      positive grade 1 EC than controls. The mRNA coding for types 4, 5, 7, 8, and 12
      17beta-HSD did not vary, whereas that coding for type 2 17beta-HSD was increased
      in high-grade lesions compared with controls. Three-dimensional ex vivo EC
      explant cultures demonstrated that 17beta-HSD type 1 generated 17beta-estradiol
      from estrone and increased tumor cell proliferation. Additional in vitro studies
      using EC cells confirmed that in the presence of 17beta-HSD type 1, estrone
      induced estrogen signaling activation similarly to 17beta-estradiol. Therefore,
      estrone was reduced to 17beta-estradiol. CONCLUSIONS: Type 1 17beta-HSD increases
      17beta-estradiol exposure in grade 1 EC, thus supporting tumor growth. This
      enzyme represents a potential therapeutic target.

PMID- 22362819
TI  - Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fibroblast growth
      factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity.
AB  - BACKGROUND: Obesity is associated with hyperparathyroidism and increased bone
      mass and turnover, but their pathogeneses are unclear. AIMS: Our aim was to
      determine in obesity interrelationships among serum levels of leptin, the mineral
      regulating hormones, bone turnover markers, and sclerostin. METHODS: This case
      control study was performed in 20 women having bariatric surgery and 20 control
      women matched for race and age. Anthropometrics and fasting serum biochemistries
      were measured in controls and in bariatric patients the morning of surgery.
      RESULTS: Body mass index (48.9 vs. 25.4 kg/m(2)), weight (128.6 vs. 71.9 kg),
      serum leptin (74.6 vs. 25.2 ng/ml), PTH (44.5 vs. 28.8 pg/ml), fibroblast growth
      factor 23 (FGF23) (42.4 vs. 25.9 pg/ml), and bone alkaline phosphatase (BAP)
      (25.8 vs. 17.5 U/liter) were higher, but height (162.3 vs. 167.7 cm) and 1,25
      dihydroxyvitamin D (1,25D) (39.2 vs. 48.7 pg/ml) were lower in bariatric surgery
      patients than controls. There was no difference in serum sclerostin, amino
      terminal collagen cross-links, 25-hydroxyvitamin D (25D), calcium, phosphate, and
      creatinine between groups. In the combined sample, leptin was positively related
      to PTH, FGF23, and BAP but not to 1,25D or sclerostin. Multiple regression
      analysis demonstrated that PTH was predicted by leptin and Ca (R(2) = 0.39);
      1,25D by 25D, FGF23, and phosphate (R(2) = 0.43); FGF23 by leptin and 1,25D (R(2)
      = 0.27); BAP by leptin, PTH, and Ca (R(2) = 0.39); and sclerostin by leptin and
      PTH (R(2) = 0.20). CONCLUSIONS: Women having bariatric surgery had higher leptin,
      PTH, FGF23, and BAP and lower 1,25D than controls. Leptin predicted the serum
      levels of PTH, 1,25D, and FGF23, the mineral-regulating hormones, and BAP, a bone
      formation marker, in women with body mass index ranging from 13.9-65.8 kg/m(2).
      The results suggest that leptin has an endocrine or paracrine effect on PTH and
      FGF23 production and that PTH may be one of the signals in obesity that leads to
      increased bone mass.

PMID- 22362822
TI  - Prevalence, incidence, and prognosis of hepatobiliary disease in community-based
      patients with type 2 diabetes: the Fremantle Diabetes Study.
AB  - CONTEXT: Few studies have examined morbidity and mortality associated with
      hepatobiliary disease in diabetes. Most have used administrative databases and/or
      have had limited/incomplete data including recognized risk factors for
      hepatobiliary disease. OBJECTIVE: The objective of the study was to explore the
      relationship between type 2 diabetes and hepatobiliary disease in well
      characterized patients with detailed risk factor data including viral hepatitis
      status and hemochromatosis genotype. DESIGN: This was a community-based
      longitudinal observational study. SETTING: The study was conducted in an urban
      Australian community. PATIENTS: The study included 1294 patients of mean +/- SD
      aged 64.1 +/- 11.3 yr and 5156 age-, gender-, and ZIP code-matched nondiabetic
      controls. MAIN OUTCOME MEASURES: Prevalent and incident hepatobiliary disease and
      hepatobiliary disease-related death were measured. Competing risks proportional
      hazard models provided independent associates of these end points. RESULTS:
      During 13,705 patient-years (mean 11.5 yr), 144 patients had an initial
      hepatobiliary disease-related hospitalization/cancer registration vs. 403
      controls during 63,937 person-years of follow-up, an incidence rate ratio of 1.66
      (95% confidence interval 1.37-2.02). Incident hepatobiliary disease was
      associated with a lower glycosylated hemoglobin and higher urinary albumin to
      creatinine ratio. Nearly half of the patients (49.9%) died during follow-up
      [crude mortality ratio vs. nondiabetic controls 1.97 (1.16-3.32)], and 21 (3.3%)
      from hepatobiliary disease including two cases of cirrhosis attributable to
      nonalcoholic steatohepatitis. Hepatobiliary disease-related death was
      independently predicted by prior hepatobiliary disease, hepatitis C
      seropositivity, retinopathy, and peripheral neuropathy; higher educational level
      and higher fasting serum glucose were protective. CONCLUSIONS: Hepatobiliary
      disease and associated mortality are increased in type 2 diabetes. Multiple
      factors including fatty infiltration, microangiopathy, and direct glucotoxicity
      are likely to contribute, but hospitalization and death due to cirrhosis from
      nonalcoholic steatohepatitis appear uncommon.

PMID- 22362823
TI  - Features of hepatic and skeletal muscle insulin resistance unique to type 1
      diabetes.
AB  - CONTEXT: Type 1 diabetes is known to be a state of insulin resistance; however,
      the tissues involved in whole-body insulin resistance are less well known. It is
      unclear whether insulin resistance is due to glucose toxicity in the post
      Diabetes Control and Complications Trial era of tighter glucose control.
      OBJECTIVE: We performed this study to determine muscle and liver insulin
      sensitivity individuals with type 1 diabetes after overnight insulin infusion to
      lower fasting glucose concentration. DESIGN, PATIENTS, AND METHODS: Fifty
      subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes
      duration 22.9 +/- 1.7 yr, without known end organ damage] were frequency matched
      on age and body mass index by group and studied. After 3 d of dietary control and
      overnight insulin infusion to normalize glucose, we performed a three-stage
      hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) . min.
      Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose.
      Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose
      rate of appearance (Ra), whereas muscle insulin sensitivity was measured using
      the glucose rate of disappearance during the highest insulin dose. RESULTS:
      Throughout the study, glucose Ra was significantly greater in individuals
      compared with those without type 1 diabetes. The concentration of insulin
      required for 50% suppression of glucose Ra was 2-fold higher in subjects with
      type 1 diabetes. Glucose rate of disappearance was significantly lower in
      individuals with type 1 diabetes during the 8- and 40-mU/m(2) . min stages.
      CONCLUSION: Insulin resistance in liver and skeletal muscle was a significant
      feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was
      not explained by body mass index, percentage fat, plasma lipids, visceral fat,
      and physical activity and was also not fully explained by hyperglycemia.

PMID- 22362824
TI  - Long-term safety of pegvisomant in patients with acromegaly: comprehensive review
      of 1288 subjects in ACROSTUDY.
AB  - CONTEXT: Pegvisomant is a GH receptor antagonist. The ACROSTUDY is a global
      safety surveillance study of long-term treatment of acromegaly with pegvisomant.
      OBJECTIVE: The objective of the study was to monitor long-term safety and
      treatment outcomes. DESIGN: ACROSTUDY is open to all patients with acromegaly who
      are treated with pegvisomant. We report an interim analysis of data captured from
      1288 subjects enrolled before a database freeze of December 31, 2009. SETTING:
      This was a global noninterventional surveillance study. MAIN OUTCOME MEASURE(S):
      Long-term monitoring of safety, including central magnetic resonance imaging
      (MRI) reading and treatment outcomes, was measured. RESULTS: Subjects (n = 1288)
      were treated with pegvisomant for a mean of 3.7 yr and followed up in ACROSTUDY
      for a mean of 2.1 yr. A total of 1147 adverse events (AE) were recorded in 477
      subjects (37%), among which 192 AE in 124 subjects (9.6%) were considered to be
      related to pegvisomant. Serious AE were recorded in 159 subjects (12.3%), whereas
      pegvisomant-related Serious AE were recorded in 26 subjects (2%). No deaths (15
      subjects; 1.2%) were attributed to pegvisomant use. The incidence of increase in
      pituitary tumor size in the subset with confirmed MRI increases on central
      reading represented 3.2% of the overall cohort with at least two available MRI (n
      = 936). Injection-site reactions were reported in 28 cases (2.2%). In 30 patients
      (2.5%), an elevated aspartate aminotransferase or alanine aminotransferase of
      more than 3 times the upper level of normality was reported. There were no
      reports of liver failure. After 5 yr of pegvisomant treatment, 63.2% of subjects
      had normal IGF-I levels at a mean dose of 18 mg/d. CONCLUSIONS: Data entered and
      evaluated in ACROSTUDY indicate that pegvisomant is an effective and safe medical
      treatment in patients with acromegaly. The reported low incidence of pituitary
      tumor size increase, liver enzyme elevations, and lipodystrophy at the injection
      site are reassuring.

PMID- 22362825
TI  - Weight cycling and risk of endometrial cancer.
AB  - BACKGROUND: Obesity, as measured by body mass index (BMI), is an established risk
      factor for endometrial cancer in postmenopausal women. Weight cycling, which
      consists of repeated cycles of weight loss followed by regain, occurs frequently
      in overweight and obese women. It is unclear whether weight cycling is associated
      with risk of endometrial cancer independent of BMI. METHODS: This analysis
      included 38,148 postmenopausal women enrolled in the Cancer Prevention Study II
      Nutrition Cohort, of whom 559 were diagnosed with endometrial cancer between
      enrollment in 1992 and June 30, 2007. Number of lifetime weight cycles was
      determined from questions on the baseline questionnaire asking how many times 10
      or more pounds were intentionally lost and later regained. Multivariable-adjusted
      hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using
      Cox proportional hazards regression. RESULTS: Weight cycling was positively
      associated with endometrial cancer incidence (RR, 2.13; 95% CI, 1.63-2.78 for 10+
      weight cycles vs. no weight cycles; P(trend) < 0.0001). However, after adjustment
      for BMI in 1992, this association was null (RR, 1.05; 95% CI, 0.77-1.42; P(trend)
      = 0.82). Weight cycling was not associated with endometrial cancer in analyses
      stratified by BMI or by weight change after adjustment for BMI. CONCLUSIONS:
      After adjustment for BMI, weight cycling was not associated with the risk of
      endometrial cancer. IMPACT: These findings suggest that weight loss with
      subsequent regain is unlikely to increase risk of endometrial cancer. Therefore,
      weight loss for better health should be encouraged.

PMID- 22362826
TI  - Use of telehealth for patients referred to a retrieval service: timing,
      destination, mode of transport, escort level and patient care.
AB  - We examined the utility of telehealth in assisting the decision-making processes
      of aeromedical coordinators, with particular focus on the timing, destination,
      mode of transport and escort level. Medical coordinators from the Northern
      Operations site of the Queensland emergency retrieval service were asked to
      complete a survey form about the changes that telehealth made to their retrieval
      decision-making process. Information was collected in six areas: diagnosis,
      severity, priority, crew, mode of transport and destination. During a 12-month
      period, there were 403 emergency referrals from the five participating sites.
      There were 136 eligible patient referrals for analysis, of which 90 did not have
      teleconsultations performed; the most common reasons were that the medical
      coordinator was too busy with other work or the new procedure was forgotten (n =
      39, 43%). The remaining 46 patients had a teleconsultation during the trial and
      44 data sheets were available for analysis. In 21 cases some component of the
      decision-making process was altered by the use of telehealth, with decisions
      being significantly altered in nine cases. Most alterations were for severity of
      patient condition, then diagnosis and priority of transfer. The use of telehealth
      was thought to be beneficial in confirming the original decision in 30 cases.
      Telehealth was not of assistance in seven cases. Telehealth appears to assist in
      accurate decision-making during the medical coordination of aeromedical
      retrievals.

PMID- 22362827
TI  - A review of Medicare expenditure in Australia for psychiatric consultations
      delivered in person and via videoconference.
AB  - We examined the activity (services recorded) and cost (benefits paid) of
      reimbursement associated with telepsychiatry services in the Australian public
      health-care sector. We reviewed the activity and costs administered through the
      government's Medicare Benefits Schedule (MBS) from July 2002 to June 2011. During
      this nine-year-period, almost 14 million psychiatric consultations were funded
      through Medicare at a cost of $1.6 billion. Of these, 8003 were telepsychiatry
      consultations which cost $934,000, i.e. the video consultations subgroup
      represented 0.06% of all psychiatric consultations provided and 0.06% of the
      total cost to the government for these services. Despite telepsychiatry being a
      widely reported and successful example of telehealth internationally, the uptake
      of telepsychiatry in Australia has been slow.

PMID- 22362828
TI  - An electronic medication reminder, supported by a monitoring service, to improve
      medication compliance for elderly people living independently.
AB  - We conducted a pilot study of a personal medication reminder unit, supported by a
      monitoring service. A total of 31 elderly residents were offered the reminder
      service for a period of eight weeks (1736 person-days of service). A telephone
      call from the monitoring service was made after four weeks to check that each
      participant was happy with the service and keen to continue. No one opted out and
      users of the service found it easy to manage, helpful and acceptable. There was a
      significant improvement (P = 0.012) in the rate of self-assessed medication
      compliance, from pre (52%) to post (81%) service introduction. There was a
      significant improvement in people's perceived ability to look after themselves at
      home (self-care ability) (P = 0.001). The percentage of participants rating their
      ability to look after themselves at home as excellent increased from 42% to 68%.
      Health-related quality of life measures, such as physical and mental health,
      showed positive improvement, but the changes were not significant. The service
      has the potential to improve health and well-being outcomes for people on
      multiple medications living independently in the community.

PMID- 22362829
TI  - Clinical use of Skype: a review of the evidence base.
AB  - Skype is a popular and free software application that allows PCs and mobile
      devices to be used for video communication over the Internet. We reviewed the
      literature to determine whether the clinical use of Skype is supported by
      evidence. One small (n = 7) controlled clinical trial had assessed the effect of
      nursing communication using Skype on elderly patients with dementia and their
      carers. However, we were unable to identify any large, well-designed studies
      which had formally evaluated the safety, clinical effectiveness, security and
      privacy of Skype for the routine delivery of patient care. While there were many
      case reports and small studies, no firm evidence either in favour of, or against
      the use of Skype for clinical telehealth was found. The risks and benefits of
      using Skype for clinical purposes are not known.

PMID- 22362830
TI  - Effect of mobile phone-based psychotherapy in suicide prevention: a randomized
      controlled trial in Sri Lanka.
AB  - We conducted a randomized controlled trial to test whether a Brief Mobile
      Treatment (BMT) intervention could improve outcomes relative to usual care among
      suicide attempters. The intervention included training in problem solving
      therapy, meditation, a brief intervention to increase social support as well as
      advice on alcohol and other drugs, and mobile phone follow-up. The effect of the
      intervention was measured in terms of a reduction in suicidal ideation,
      depression and self-harm at Baseline, six and 12 months. A wait-list control
      group received usual care. A total of 68 participants was recruited from a Sri
      Lankan hospital following a suicide attempt. Participants who received the
      intervention were found to achieve significant improvements in reducing suicidal
      ideation and depression than those receiving usual care. The BMT group also
      experienced a significant improvement of social support when compared to the
      control group. However, the BMT group did not demonstrate a significant effect in
      reducing actual self-harm and most substance use, and differential effects on
      alcohol use were restricted to men. Although the present study was limited in
      revealing which component of the intervention was more effective in preventing
      suicide, it showed its efficacy in reducing suicide as a whole.

PMID- 22362831
TI  - Feasibility and accuracy of medication checks via Internet video.
AB  - We investigated the feasibility and accuracy of using Internet-based
      videoconferencing for double-checking medications. Ten participants checked 30
      different medications using a desktop PC and a webcam. The accuracy of the video
      based checks was compared with 'face-to-vial' checks. The checks included the
      drug name, dosage and expiry dates of ampoules, vials and tablets, as well as
      graduations on syringes. There was 100% accuracy for drug name, dosage, and
      graduations on syringes greater than 1 unit. The expiry dates proved more
      difficult to read, and accuracy was only 63%. The mean overall accuracy was 91%
      for all items. Internet video-based medication double-checks may have a useful
      role to play in processes to ensure the safe use of medications in home care.

PMID- 22362832
TI  - A review of telemedicine interventions in diabetes care.
AB  - We reviewed the literature concerning the use of telemedicine interventions in
      diabetes care. The PubMed database was searched for randomized controlled trials
      concerning the use of telemedicine for patients with type 1 or type 2 diabetes. A
      total of 27 articles (studies) met the inclusion criteria. The interventions
      concerned videoconferencing (n = 8), mobile phones (n = 10) and telephone calls
      (n = 9). There was metabolic improvement in 23 studies, which was significant in
      12 out of 23 (44%). Only two studies (8%) reported a negative clinical outcome.
      The majority of the studies (n = 19; 70%) employed behavioural therapy as the key
      intervention. The medium used for interaction in behavioural therapy intervention
      was videoconferencing (n = 7), mobile phone (n = 4), telephone calls (n = 8),
      feedback letters (n = 2). Telemedicine appears to be a promising alternative to
      conventional therapy.

PMID- 22362833
TI  - The potential of telehealth for 'business as usual' in outpatient clinics.
AB  - A six-month pilot study was conducted to ascertain the value of using high
      definition videoconferencing equipment in an outpatients' setting. The
      videoconferencing equipment, which included digital biometric equipment, was
      installed in the outpatient clinics of a remote health service in New Zealand.
      Use of the equipment was evaluated using action research techniques. Clinicians
      were interviewed about their assessment of the equipment's usefulness. Patients
      and their carers completed questionnaires about their clinic experience. During
      the pilot trial, 109 patients were seen in 25 clinics of six different
      specialities. Questionnaire results showed that patients and their companions had
      a good user experience, similar to a face-to-face appointment. Clinicians found
      that the large screen, sense of proximity, video clarity and definition, and lack
      of sound/picture lag worked well for certain types of outpatients' clinics, e.g.
      methadone maintenance clinics. The need for process changes made it difficult to
      turn telehealth into business as usual in an environment built for face-to-face
      appointments. We conclude that videoconference equipment has potential to become
      integral to outpatients' clinics.

PMID- 22362834
TI  - Readiness of health-care institutions in KwaZulu-Natal to implement
      telepsychiatry.
AB  - We assessed the preparedness of health districts and designated hospitals in the
      KwaZulu-Natal (KZN) province for proposed telepsychiatry services. An e-health
      readiness questionnaire for developing countries was administered to managers of
      health districts and managers of designated psychiatric hospitals by telephone
      interview. Ten of the 11 district managers and managers/medical officers of 45 of
      58 designated hospitals were interviewed. Notwithstanding some concerns regarding
      the tool, low levels of e-health readiness were found. District managers recorded
      e-health readiness scores of 137-217 out of 300. This was similar to the hospital
      managers, who recorded readiness scores of 121-260 out of 300. For telepsychiatry
      to succeed in KZN, an awareness programme will be required to facilitate the
      necessary change management.

PMID- 22362835
TI  - A pilot health information management system for public health midwives serving
      in a remote area of Sri Lanka.
AB  - We developed an electronic Health Information Management System (HIMS) for Public
      Health Midwives (PHMs) in Sri Lanka. We conducted a needs analysis amongst 16
      PHMs, which found that they spent most of their time managing health records. The
      HIMS was designed so that it could accept data from the PHMs, and generate
      reports which could be used by the PHMs themselves as well as by their
      supervisors. The HIMS was trialled by a group of 16 PHMs in a remote area of the
      Ratnapura district of Sri Lanka. Mini-laptops with the software were distributed
      to the PHMs and they were given the necessary training. They started entering
      historical data from the registers into the system by themselves. Nearly 10,000
      public health records were generated in the first three months. In a subsequent
      survey, the PHMs all gave positive answers indicating that they were happy with
      the pilot system, they would like to continue using it to enhance their service
      and they wanted to see it expanded across the whole of Ratnapura district. The
      system seems to be a practical solution for the field activities of PHMs in Sri
      Lanka.

PMID- 22362836
TI  - The Rowland Universal Dementia Assessment Scale (RUDAS) as a reliable screening
      tool for dementia when administered via videoconferencing in elderly post-acute
      hospital patients.
AB  - The Rowland Universal Dementia Assessment Scale (RUDAS) is a six-domain screening
      tool for dementia. We measured the practicality and reliability of administering
      the RUDAS in a telemedicine setting. Inpatients were recruited from a Geriatric
      and Rehabilitation Unit. Each patient was administered the RUDAS both face-to
      face (FTF) and via videoconferencing (VC). The assessment format (FTF or VC) and
      the allocation of doctor (Doctor 1 or Doctor 2) to format were randomized. Scores
      from each assessment format were compared. The outcome of no difference was
      decided based on a difference in mean of no more than +/- one point. Percentage
      agreement (agreement being +/-2 points) was calculated on individual test scores.
      Forty-two patients (average age 75 years) completed the two assessments. Their
      mean Mini-Mental State Examination (MMSE) score was 24.7 (range 10-30). The mean
      RUDAS score for both FTF and VC assessment was 24.9 (difference between the means
      0.04), i.e. there was no significant difference. The results suggest that the
      RUDAS can be reliably administered via VC in post acute patients as an
      alternative to FTF administration.

PMID- 22362837
TI  - Telehealth for nursing homes: the utilization of specialist services for
      residential care.
AB  - Specialist care consultations were identified by two research nurses using
      documentation in patient records, appointment diaries, electronic billing
      services and on-site observations at a 441-bed long term care facility. Over a
      six-month period there were 3333 consultations (a rate of 1511 consultations per
      year per 100 beds). Most consultations were for general practice (n = 2589, 78%);
      these consultations were mainly on site (99%), with only 27 taking place off
      site. There were 744 consultations for specialities other than general practice.
      A total of 146 events related to an emergency or unplanned hospital admission.
      The remaining medical consultations (n = 598, 18%) related to 23 medical
      specialities. The largest number of consultations were for surgery (n = 106),
      podiatry (n = 100), nursing services including wound care (n = 74), imaging (n =
      41) and ophthalmology (n = 40). Many services which are currently being provided
      on site to metropolitan long-term care facilities could be provided by telehealth
      in both urban and rural facilities.

PMID- 22362838
TI  - Results of a telehealth-enabled chronic care management service to support people
      with long-term conditions at home.
AB  - Both congestive heart failure and chronic obstructive pulmonary disease are more
      common among Maori than non-Maori people, and the cultural acceptability of home
      based remote monitoring technology has not been tested. We conducted a 12-month
      pilot trial of home telemonitoring. Patients were randomly assigned to the
      control and intervention groups. Patients in the control group showed no clear
      differences in quality of life at the end of the trial. The telehealth group
      showed a consistent trend towards improved quality of life on several
      instruments, including the SF-36, the St George Respiratory Questionnaire and the
      K10 questionnaire; the improvement in the latter was significant.
      Hospitalizations were reduced in both the control (-19%) and telehealth group (
      25%). Patient interviews indicated that the technology was acceptable to most
      patients and their families, including the Maori. The results from the pilot
      trial suggest that wider implementation with a cost benefit evaluation could be
      worthwhile.

PMID- 22362839
TI  - Job stressors and smoking cessation among Malaysian male employees.
AB  - BACKGROUND: Job stressors may reduce the likelihood of quitting smoking. AIMS: To
      assess the association between job strain, smoking behaviour and smoking
      cessation among Malaysian male employees involved in a smoking cessation
      programme. METHODS: The study was conducted among employees in two major public
      universities in Malaysia. All staff from both universities received an invitation
      to participate in this study. At the start of treatment, participants completed a
      questionnaire on sociodemographic variables, smoking habits and the Malay version
      of the Job Content Questionnaire (JCQ). The JCQ consists of scales of job
      control, job demand, supervisor support, co-worker support, job insecurity, job
      decision latitude and job skill discretion. Behaviour therapy with free nicotine
      replacement therapy (NRT) was given as treatment for two months. Participants
      were contacted at 1 week, 3 months and 6 months to determine their smoking
      status. RESULTS: One hundred and eighty five staff from both universities
      responded and voluntarily showed interest in quitting. At three months (OR =
      8.96; 95% CI: 1.14-70.76) and six months (OR = 8.9; 95% CI: 1.15-68.65), men with
      higher co-workers' support demonstrated a higher likelihood of quitting. Smokers
      in a 'passive job' also demonstrated higher likelihood of quitting compared with
      those working in the 'low strain' category at six months (OR = 9.92; 95% CI: 1.20
      82.68). No meaningful associations were found between other psychosocial job
      variables and smoking cessation. CONCLUSIONS: A positive relationship with and
      support from co-workers are important factors for workplace smoking cessation.

PMID- 22362840
TI  - Aetiological relationships of nasal mucus cyclic nucleotides in patients with
      taste and smell dysfunction.
AB  - AIMS: The authors previously demonstrated that nasal mucus cyclic adenosine 3',
      5'-monophosphate (cAMP) and cyclic 3', 5'-guanosine monophosphate (cGMP) were
      lower in patients with smell and taste dysfunction than in normal individuals. To
      learn more about these differences this study related levels of nasal mucus cAMP
      and cGMP in patients with smell and taste dysfunction to the aetiology of their
      sensory loss and compared these results with those in normal individuals.
      METHODS: Nasal mucus cAMP and cGMP levels in patients with smell loss (hyposmia)
      were calculated after assembling data into aetiological groups. Levels were
      compared with each clinical group, with the entire patient group and with normal
      individuals. Data were obtained from initial values among patients with hyposmia
      who participated in a clinical trial of treatment with the phosphodiesterase
      inhibitor theophylline. RESULTS: Nasal mucus cyclic nucleotides in the entire
      patient group before treatment were below normal as previously demonstrated.
      Stratification by aetiology revealed differences not previously apparent. In some
      groups levels of cAMP and cGMP were below normal, some were similar to normal and
      some were above the normal mean. CONCLUSIONS: As nasal mucus cyclic nucleotides
      relate to the growth and development of olfactory epithelial cells these results
      indicate there are differential alterations in nasal mucus cAMP and cGMP related
      to the aetiology of smell and taste dysfunction.

PMID- 22362842
TI  - Thiol modulation of the chloroplast ATP synthase is dependent on the energization
      of thylakoid membranes.
AB  - Thiol modulation of the chloroplast ATP synthase gamma subunit has been
      recognized as an important regulatory system for the activation of ATP hydrolysis
      activity, although the physiological significance of this regulation system
      remains poorly characterized. Since the membrane potential required by this
      enzyme to initiate ATP synthesis for the reduced enzyme is lower than that needed
      for the oxidized form, reduction of this enzyme was interpreted as effective
      regulation for efficient photophosphorylation. However, no concrete evidence has
      been obtained to date relating to the timing and mode of chloroplast ATP synthase
      reduction and oxidation in green plants. In this study, thorough analysis of the
      redox state of regulatory cysteines of the chloroplast ATP synthase gamma subunit
      in intact chloroplasts and leaves shows that thiol modulation of this enzyme is
      pivotal in prohibiting futile ATP hydrolysis activity in the dark. However, the
      physiological importance of efficient ATP synthesis driven by the reduced enzyme
      in the light could not be demonstrated. In addition, we investigated the
      significance of the electrochemical proton gradient in reducing the gamma subunit
      by the reduced form of thioredoxin in chloroplasts, providing strong insights
      into the molecular mechanisms underlying the formation and reduction of the
      disulfide bond on the gamma subunit in vivo.

PMID- 22362841
TI  - Neuronal correlates of social cognition in borderline personality disorder.
AB  - Patients with borderline personality disorder (BPD) have severe problems in
      social interactions that might be caused by deficits in social cognition. Since
      the findings about social-cognitive abilities in BPD are inhomogeneous, ranging
      from deficits to superior abilities, we aimed to investigate the neuronal basis
      of social cognition in BPD. We applied a paradigm with three social cognition
      tasks, differing in their complexity: basal processing of faces with a neutral
      expression, recognition of emotions, and attribution of emotional intentions
      (affective ToM). A total of 13 patients with BPD and 13 healthy matched controls
      (HCs) were included in a functional magnet resonance imaging study. BPD patients
      showed no deficits in social cognition on the behavioral level. However, while
      HCs showed increasing activation in areas of the mirror neuron system with
      increasing complexity in the social-cognitive task, BPD patients had
      hypoactivation in these areas and hyperactivation in the amygdala which were not
      modulated by task complexity. This activation pattern seems to reflect an
      enhanced emotional approach in the processing of social stimuli in BPD that
      allows good performance in standardized social-cognitive tasks, but might be the
      basis of social-cognitive deficits in real-life social interactions.

PMID- 22362843
TI  - Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
AB  - A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial
      Hypertension) was undertaken to analyse prevalence, incidence and survival of
      pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary
      hypertension (CTEPH) in Spain, and to assess the applicability of recent survival
      prediction equations. Voluntary reporting of previously diagnosed and incident
      PAH or CTEPH cases (July 2007-June 2008) was performed. Demographic, functional
      and haemodynamic variables were evaluated. 866 patients with PAH and 162 with
      CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno
      occlusive disease were reported for the first time in a PAH registry. Estimated
      prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult
      inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9
      cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%,
      respectively, with no differences between PAH and CTEPH. Male sex, right atrial
      pressure and cardiac index were independent predictors of death. Matching between
      observed survival and that predicted by different equations was closer when the
      characteristics of the cohorts were similar. Epidemiology and survival of PAH
      patients in the Spanish registry are similar to recent registries.
      Characteristics of the population from which survival prediction equations are
      derived influence their applicability to a different cohort. CTEPH is much less
      prevalent than PAH, although has a similar survival rate.

PMID- 22362844
TI  - Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of
      pulmonary arterial hypertension.
AB  - In this phase 2 proof-of-concept study we examined the safety and efficacy of
      selexipag, an orally available, selective prostacyclin receptor (IP receptor)
      agonist, as a treatment for pulmonary arterial hypertension (PAH). 43 adult
      patients with symptomatic PAH (receiving stable endothelin receptor antagonist
      and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one
      to receive either selexipag or placebo. Dosage was up-titrated in 200-MUg
      increments from 200 MUg twice daily on day 1 to the maximum tolerated dose by day
      35 (maximum allowed dose of 800 MUg twice daily). Change in pulmonary vascular
      resistance at week 17 expressed as a percentage of the baseline value was the
      primary efficacy end-point, and was analysed in the per protocol set first and
      then in the all-treated set to assess robustness of results. A statistically
      significant 30.3% reduction in geometric mean pulmonary vascular resistance was
      observed after 17 weeks' treatment with selexipag compared with placebo (95%
      confidence limits -44.7- -12.2; p=0.0045, Wilcoxon rank sum test). This was
      supported by a similar result from the all-treated set. Selexipag was well
      tolerated with a safety profile in line with the expected pharmacological effect.
      Our results encourage the further investigation of selexipag for the treatment of
      PAH.

PMID- 22362845
TI  - Indoor air pollution and the lung in low- and medium-income countries.
AB  - Over half the world's population, mostly from developing countries, use solid
      fuel for domestic purposes and are exposed to very high concentrations of harmful
      air pollutants with potential health effects such as respiratory problems,
      cardiovascular problems, infant mortality and ocular problems. The evidence also
      suggests that, although the total percentage of people using solid fuel is
      decreasing, the absolute number is currently increasing. Exposure to smoke from
      solid fuel burning increases the risk of chronic obstructive pulmonary disease
      (COPD) and lung cancer in adults, and acute lower respiratory tract
      infection/pneumonia in children. Despite the heterogeneity among studies, the
      association between COPD and exposure to smoke produced by burning different
      types of solid fuel is consistent. However, there is strong evidence that while
      coal burning is a risk factor for lung cancer, exposure to other biomass fuel
      smoke is less so. There is some evidence that reduction of smoke exposure using
      improved cooking stoves reduces the risk of COPD and, possibly, acute lower
      respiratory infection in children, so approaches to reduce biomass smoke exposure
      are likely to result in reductions in the global burden of respiratory disease.

PMID- 22362846
TI  - Atorvastatin in pulmonary arterial hypertension (APATH) study.
AB  - Statins have been shown to both prevent and attenuate pulmonary hypertension in
      animal models. This study investigates the potential therapeutic benefits of
      atorvastatin as an affordable treatment for pulmonary hypertension patients. 220
      patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic
      pulmonary hypertension (CTEPH) were randomised, double-blind, to receive
      atrovastatin 10 mg daily or matching placebo in addition to supportive care. At 6
      months, 6-min walk distance decreased by 16.6 m in the atorvastatin group and
      14.1 m in the placebo group. The mean placebo-corrected treatment effect was -2.5
      m (95% CI: -38-33; p=0.96), based on intention to treat. A small nonsignificant
      increase in pulmonary vascular resistance and fall in cardiac output was seen in
      both treatment groups. There was no significant difference in the proportion of
      patients who improved, remained stable or showed a deterioration in World Health
      Organization functional class between atorvastatin and placebo treatments. Nine
      patients died in the atorvastatin group and 11 in the placebo group. Serum
      cholesterol levels fell significantly on atorvastatin treatment. Discontinuation
      rates were 23.2% and 26.9% on atorvastatin and placebo, respectively.
      Atorvastatin 10 mg daily has no beneficial effect on the natural history of PAH
      or CTEPH over 6 months.

PMID- 22362847
TI  - High inhaled corticosteroids adherence in childhood asthma: the role of
      medication beliefs.
AB  - Our aim was to study determinants of adherence in young asthmatic children over a
      3-month period, including the role of parental illness and medication perceptions
      as determinants of adherence. Consecutive 2-6-yr-old children with asthma, using
      inhaled corticosteroids (ICS), followed-up at our paediatric asthma clinic (where
      patients are being extensively trained in self-management, and are followed-up
      closely) were enrolled. Adherence was measured electronically using a
      Smartinhaler(r) and calculated as a percentage of the prescribed dose. We
      examined the association of adherence to a range of putative determinants,
      including clinical characteristics and parental perceptions about illness and
      medication. Median (interquartile range) adherence, measured over 3 months in 93
      children, was 92 (76-97)%, and most children had well controlled asthma. 94% of
      parents expressed the view that giving ICS to their child would protect him/her
      from becoming worse. Adherence was significantly associated with asthma control
      and with parental perceptions about medication. The high adherence rate observed
      in our study was associated with parental perceptions about ICS need. The high
      perceived need of ICS may probably be ascribed to the organisation of asthma care
      (with repeated tailored education and close follow-up).

PMID- 22362848
TI  - Inhibitory effects of tiotropium on rhinovirus infection in human airway
      epithelial cells.
AB  - Infection by rhinoviruses (RVs) causes exacerbations of chronic obstructive
      pulmonary disease (COPD). The long-acting anti-cholinergic agent tiotropium
      reduces the frequency of COPD exacerbations, but the inhibitory effects of
      tiotropium on the COPD exacerbations induced by RVs are unclear. Likewise, the
      effects of tiotropium on RVs infection remain to be studied. To examine the
      effects of tiotropium on RV infection and RV infection-induced airway
      inflammation, human tracheal epithelial cells were infected with a major group
      RV, type 14 RV (RV14). RV14 infection increased the viral titre and the amount of
      pro-inflammatory cytokines, including interleukin (IL)-1beta and -6, in
      supernatant fluids and the amount of RV14 RNA in cells. Tiotropium reduced RV14
      titres, RNA and cytokine concentrations, and susceptibility to RV14 infection.
      Tiotropium reduced the expression of intercellular adhesion molecule (ICAM)-1,
      the receptor for RV14, and the number of cellular acidic endosomes, which allow
      RV14 RNA to enter the cytoplasm. Tiotropium inhibited the activation of nuclear
      factor-(kappa)B proteins, including p50 and p65, in the nuclear extracts, and it
      increased the cytosolic amount of inhibitory kappaB-alpha. Tiotropium may inhibit
      RV14 infection by reducing the levels of ICAM-1 and acidic endosomes and may also
      modulate airway inflammation in rhinovirus infection.

PMID- 22362850
TI  - Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial
      hypertension.
AB  - Immune mechanisms and autoimmunity seem to play a significant role in idiopathic
      pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the
      pathophysiology is still unclear. Recent evidence has demonstrated a detrimental
      involvement of leptin in promoting various autoimmune diseases by controlling
      regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is
      currently unknown. We hypothesised that leptin, synthesised by dysfunctional
      pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by
      regulating circulating regulatory T-lymphocytes function. First, we collected
      serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma
      associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we
      recovered tissue samples and cultured endothelial cells after either surgery or
      transplantation in controls and IPAH patients, respectively. Our findings
      indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls.
      Circulating regulatory T-lymphocyte numbers were comparable in all groups, and
      the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH
      compared with controls, whereas their function was reduced in IPAH and SSc-PAH
      patients compared with controls, in a leptin-dependent manner. Furthermore,
      endothelial cells from IPAH patients synthesised more leptin than controls. Our
      data suggest that endothelial-derived leptin may play a role in the
      immunopathogenesis of IPAH.

PMID- 22362849
TI  - Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in
      HIV-infected hospitalised patients.
AB  - Lack of point-of-care tests for tuberculosis (TB) result in diagnostic delay, and
      increased mortality and healthcare-related costs. The urine Determine(TM) TB-LAM
      point-of-care strip-test was evaluated in 335 prospectively-recruited
      hospitalised patients with suspected TB-HIV co-infection (group 1) and from 88
      HIV-infected hospitalised patients with non-TB diagnoses (group 2). Cut-off point
      specific analyses were performed using: 1) a microbiological reference standard
      (culture positive versus negative); and 2) a composite reference standard
      (exclusion of patients with clinical-TB from the culture-negative group). Using
      the microbiological reference and the manufacturer-recommended grade-1 cut-off
      point, LAM sensitivity and specificity was 66% (95% CI 57-74%). By contrast,
      using the composite reference sensitivity was 60% (95% CI 53-67%) and specificity
      improved to 96% (95% CI 89-100%) (p=0.001). The same pattern was seen when the
      grade-2 cut-off point was used (specificity 75% versus 96%; p=0.01). In group two
      patients specificity was poor using the grade-1 cut-off point, but improved
      significantly when the grade-2 cut-off point was used (90% versus 99%; p=0.009).
      The grade-2 cut-off point also offered superior inter-reader reliability
      (p=0.002). Sensitivity was highest in those with a CD4 <200 cells per mL. LAM
      combined with smear-microscopy was able to rule-in TB in 71% of Mycobacterium
      tuberculosis culture-positive patients. This preliminary study indicates that the
      LAM strip-test may be a potentially useful rapid rule-in test for TB in
      hospitalised patients with advanced immunosuppression. The grade 2, but not the
      manufacturer-recommended grade 1 cut-off point, offered superior rule-in utility
      and inter-reader reliability. Larger studies to evaluate cut-off points and
      diagnostic accuracy are urgently required.

PMID- 22362851
TI  - Cycling to work in London and inhaled dose of black carbon.
AB  - Modelling studies suggest that urban cycling is associated with an increased
      inhaled dose of fossil fuel-derived black carbon (BC). Using the amount of black
      material in airway macrophages as a marker of long-term inhaled BC, we sought to
      compare inhaled BC dose in London (UK) cyclists and non-cyclists. Airway
      macrophage carbon was assessed in 28 (58%) out of 48 healthy adults (14 cyclists
      and 14 non-cyclists) who attended for induced sputum. Short-term (24 h) exposure
      to BC was assessed on a representative working day in 27 out of 28 subjects.
      Serum interleukin (IL)-1beta, IL-2, IL-6, IL-8, granulocyte-macrophage colony
      stimulating factor and tumour necrosis factor (TNF)-alpha were assessed in 26 out
      of the 28 subjects. Cyclists were found to have increased airway macrophage
      carbon when compared with non-cyclists (mean +/- se 1.81 +/- 0.21 versus 1.11 +/-
      0.07 MUm(2); p<0.01). Short-term monitoring showed no difference in 24 h BC
      exposure between the two groups. However, cyclists were exposed to higher
      concentrations of BC during commuting (p<0.01). Airway macrophage carbon was
      associated with monitored commute BC (n=28; r=0.47, p<0.05). TNF-alpha was found
      to be increased in cyclists (p<0.05), but no other cytokines were increased.
      Commuting to work by bicycle in London is associated with increased long-term
      inhaled dose of BC. Whether cycling per se increases inhaled BC dose remains
      unclear.

PMID- 22362852
TI  - The effect of airway pressure and oscillation amplitude on ventilation in pre
      term infants.
AB  - We determined the effect of lung recruitment and oscillation amplitude on
      regional oscillation volume and functional residual capacity (FRC) in high
      frequency oscillatory ventilation (HFOV) used in pre-term infants with
      respiratory distress syndrome (RDS). Changes in lung volume, oscillation volume
      and carbon dioxide levels were recorded in 10 infants during a stepwise
      recruitment procedure, and an increase in pressure amplitude of 5 cmH(2)O was
      measured using electrical impedance tomography and transcutaneous monitoring. The
      pressures at maximal respiratory system compliance, maximal oscillation volume
      and minimal carbon dioxide levels were determined. Impedance data were analysed
      for the chest cross-section and predefined regions of interest. Despite the fixed
      pressure amplitude, the oscillation volume changed during the incremental
      pressure steps following a parabolic pattern, with an inverse relationship to the
      carbon dioxide pressures. The pressures corresponding with maximal compliance,
      maximal oscillation volume and minimal carbon dioxide were similar and highly
      correlated. Regional analysis showed similar findings. The increase in pressure
      amplitude resulted in increased oscillation volumes and decreased carbon dioxide
      levels, while FRC remained unchanged. In HFV pre-term infants with RDS,
      oscillation volumes are closely related to the position of ventilation in the
      pressure-volume envelope and the applied pressure amplitude. Changes in pressure
      amplitude do not seem to affect FRC.

PMID- 22362853
TI  - Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism.
AB  - Sleep-disordered breathing (SDB) may trigger thromboembolic events by enhancing
      intravascular clot formation. The primary objective of the present nested case
      control study was to investigate whether the prevalence of SDB is increased in
      patients with deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). 82
      consecutive patients with DVT and/or PE (cases) were prospectively enrolled
      irrespective of SDB-related symptoms and formed matched pairs with patients
      without DVT and/or PE (controls) according to sex and pre-defined categories of
      age and body mass index. The prevalence of SDB (respiratory disturbance index
      assessed by polygraphy >= 15 events.h(-1)) was significantly greater in the cases
      with DVT and/or PE than in controls (40 versus 26%, p=0.046) and was
      predominantly obstructive in nature. Multiple regression analysis revealed that
      SDB was significantly associated with DVT and/or PE (OR 2.28, 95% CI 1.08-4.85;
      p=0.032) independent of established risk factors for thrombosis. In the sex
      specific analyses this association was significant in females (OR 4.14, 95% CI
      1.05-16.36; p=0.042), but not in males (OR 1.55, 95% CI 0.57-4.21; p=0.391). SDB
      occurs more frequently in females with DVT and/or PE than in controls matched for
      anthropometric variables, and is independently associated with the occurrence of
      these thromboembolic events.

PMID- 22362854
TI  - Quadriceps wasting and physical inactivity in patients with COPD.
AB  - Quadriceps weakness is an important complication of advanced chronic obstructive
      pulmonary disease (COPD) but few data exist concerning muscle bulk in early
      disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus
      femoris cross-sectional area (USRF(CSA)), would be reduced in mild, as well as
      advanced, COPD compared with controls, and would correlate with physical
      activity. 161 patients with stable COPD and 40 healthy subjects had a measurement
      of USRF(CSA) and wore a multisensor armband to record physical activity.
      USRF(CSA) was reduced in Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II-IV
      patients had reduced USRF(CSA) (p<0.0001) compared with controls but were not
      significantly different from those with stage I disease. Physical activity level
      was reduced in stage I (p=0.002) and stage II-IV disease compared with controls.
      Using regression analysis, physical activity level was independently associated
      with USRF(CSA) in stage I (p=0.01) but not stage II-IV disease, where residual
      volume to total lung capacity ratio was the only independent predictor of
      physical activity level. Quadriceps wasting exists in patients with mild, as well
      as advanced, COPD, and is independently associated with physical inactivity in
      GOLD stage I disease. The identification of these patients may guide early
      lifestyle and therapeutic interventions.

PMID- 22362855
TI  - Paediatrics in Amsterdam.
AB  - The aim of this update is to describe the paediatric highlights from the 2011
      European Respiratory Society (ERS) Annual Congress in Amsterdam, the Netherlands.
      Abstracts from all seven groups of the ERS Paediatric Assembly (Paediatric
      Respiratory Physiology, Paediatric Asthma and Allergy, Cystic Fibrosis,
      Paediatric Respiratory Infection and Immunology, Neonatology and Paediatric
      Intensive Care, Paediatric Respiratory Epidemiology, and Paediatric Bronchology)
      are presented in the context of current literature.

PMID- 22362856
TI  - Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect
      severity of apnoeic episodes.
AB  - Plasma von Willebrand factor (VWF), produced in and released from vascular
      endothelial cells by various stimuli including hypoxia, induces platelet
      aggregation under high shear stress and plays dual pivotal roles in haemostasis
      and thrombosis within arterioles, which are regulated by the size of vWF
      multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased
      risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We
      examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag),
      VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like,
      metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA
      patients were enrolled. Blood samples were collected before sleep, after sleep,
      and after one night of nasal continuous positive airway pressure therapy. Based
      on VWFM analysis, OSA patients were classified into three groups; consistently
      normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at
      06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3,
      n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB
      followed a similar pattern. We observed a significant decrease in platelet count
      between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced
      larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to
      an arterial pro-thrombotic state.

PMID- 22362857
TI  - Occlusion pressure analysis role in partitioning of pulmonary vascular resistance
      in CTEPH.
AB  - Flow-directed pulmonary artery occlusion is posited to enable partitioning of
      vascular resistance into small and large vessels. As such it may have a role in
      assessment for pulmonary endarterectomy. To test if the occlusion technique
      distinguished small from large vessel disease we studied 59 subjects with chronic
      thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary arterial
      hypertension (IPAH), and connective tissue disease (CTD)-associated PAH. At right
      heart catheterisation, occlusion pressures were recorded. With fitting of the
      pressure decay curve, pulmonary vascular resistance was partitioned into
      downstream (small vessels) and upstream (large vessels, Rup). 47 patients
      completed the study; 14 operable CTEPH, 15 inoperable CTEPH, 13 idiopathic or CTD
      PAH and five post-operative CTEPH. There was a significant difference in mean Rup
      in the proximal operable CTEPH group 87.3 (95% CI 84.1-90.5); inoperable CTEPH
      mean 75.8 (95% CI 66.76-84.73), p=0.048; and IPAH/CTD, mean 77.1 (95% CI 71.86
      82.33), p=0.003. Receiver operating characteristic curves to distinguish operable
      from inoperable CTEPH demonstrated an area under the curve of 0.75, p=0.0001. A
      cut-off of 79.3 gave 100% sensitivity (95% CI 73.5-100%) but 57.1% specificity
      (95% CI 28.9-82.3%). In a subgroup analysis of multiple lobar sampling there was
      demonstrable heterogeneity. Rup is significantly increased in operable proximal
      CTEPH compared with non-operable distal CTEPH and IPAH/CTD-PAH. Rup variability
      in patients with CTEPH and PAH is suggestive of pathophysiological heterogeneity.

PMID- 22362858
TI  - Lung transplantation in children and young adults: a 20-year single-centre
      experience.
AB  - Lung transplantation in adults is an accepted therapeutic option, whereas there
      is ongoing debate on its positive impact on survival in children. We report our
      experience of the first 20 yrs of paediatric lung transplantation at a single
      centre in Austria. Patient survival, organ survival and freedom from
      bronchiolitis obliterans were estimated by Kaplan-Meier curves. Pre- and post
      transplant parameters were assessed and their influence on patient and organ
      survival evaluated by univariate tests and stepwise multivariate analyses. A
      total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient
      survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were
      found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant.
      Analysing different eras of transplantation suggests an improvement over the
      years with a 5-yr survival rate of 70.6% in the second decade. A positive effect
      of pre-transplant diabetes mellitus and immunosuppression was found with the
      newer drug tacrolimus, and a negative effect of pre-transplant in-hospital
      admission was reported. A high rate of successful re-transplantation prolonged
      total patient survival.

PMID- 22362859
TI  - 24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated
      with inhaled corticosteroids.
AB  - Current guidelines recommend adding a long-acting inhaled beta(2)-agonist (LABA)
      to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study
      evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma
      patients who remained symptomatic despite existing ICS therapy. The study
      involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25,
      12.5, 25 and 50 MUg), administered once daily in the evening by dry powder
      inhaler for 28 days, in asthma patients aged >= 12 yrs symptomatic on current ICS
      therapy. The primary end-point was trough (24 h post-dose) forced expiratory
      volume in 1 s (FEV(1)); secondary end-points were weighted mean FEV(1), peak
      expiratory flow (PEF), symptom-/rescue-free 24-h periods, and safety. A
      significant relationship was observed between VI dose and improvements in trough
      FEV(1) (p=0.037). Statistically significant increases in mean trough FEV(1),
      relative to placebo, were documented for VI 12.5-50 MUg (121-162 mL; p <= 0.016).
      Dose-related effects of VI were observed on weighted mean (0-24 h) FEV(1),
      morning/evening PEF, and symptom-/rescue-free 24-h periods. All doses of VI were
      well tolerated with low incidences of recognised LABA-related adverse events
      (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-<1%).
      Once-daily VI 12.5-50 MUg resulted in prolonged bronchodilation of at least 24 h
      with good tolerability in asthma patients receiving ICS. Based on the overall
      efficacy and adverse event profile from this study, the optimum dose of VI
      appears to be 25 MUg.

PMID- 22362860
TI  - Dietary patterns and respiratory symptoms in pre-school children: the Generation
      R Study.
AB  - Overall diet in early childhood may affect the development of respiratory
      symptoms. This study examined whether childhood dietary patterns are associated
      with respiratory symptoms in Dutch pre-school children, and whether this
      association could be explained by energy intake. A prospective cohort study was
      performed in 2,173 children aged <= 4 yrs. Data on asthma-related symptoms were
      obtained by questions from the age-adapted version of the "International Study of
      Asthma and Allergies in Childhood" questionnaires. Data on respiratory tract
      infections, defined as episodes of physician attended fever with respiratory
      symptoms, was obtained by questionnaire. Principal components analysis was used
      to develop dietary patterns at 14 months of age. Compared with low adherence,
      high adherence to the "Western" dietary pattern was significantly associated with
      frequent wheeze at 3 yrs of age (relative risk (RR) 1.39, 95% CI 1.02-1.89) and
      frequent shortness of breath (RR 1.44, 95% CI 1.03-2.01) and respiratory tract
      infections (RR 1.54, 95% CI 1.08-2.19) at 4 yrs of age. However, this association
      was partially explained by energy intake. A "Western" diet may increase the risk
      of frequent respiratory symptoms at 3 and 4 yrs of age. In some measure, this
      association was explained by energy intake.

PMID- 22362861
TI  - Pulmonary hypertension in lymphangioleiomyomatosis: characteristics in 20
      patients.
AB  - This retrospective, multicentre study evaluated patients with
      lymphangioleiomyomatosis (LAM) and pre-capillary pulmonary hypertension (PH) by
      right heart catheterisation. It was conducted in 20 females with a mean +/- SD
      age of 49 +/- 12 yrs and a mean +/- SD time interval between LAM and PH diagnoses
      of 9.2 +/- 9.8 yrs. All, except for one patient, were receiving supplemental
      oxygen. 6-min walking distance was mean +/- SD 340 +/- 84 m. Haemodynamic
      characteristics were: mean pulmonary artery pressure (PAP) 32 +/- 6 mmHg, cardiac
      index 3.5 +/- 1.1 L . min(-1) . m(-2) and pulmonary vascular resistance (PVR) 376
      +/- 184 dyn . s . cm(-5). Mean PAP was >35 mmHg in only 20% of cases. The forced
      expiratory volume in 1 s was 42 +/- 25%, carbon monoxide transfer factor was 29
      +/- 13%, and arterial oxygen tension (P(a,O(2))) was 7.4 +/- 1.3 kPa in room air.
      Mean PAP and PVR did not correlate with P(a,O(2)). In six patients who received
      oral pulmonary arterial hypertension (PAH) therapy, the PAP decreased from 33 +/-
      9 mmHg to 24 +/- 10 mmHg and the PVR decreased from 481 +/- 188 dyn . s . cm(-5)
      to 280 +/- 79 dyn . s . cm(-5). The overall probability of survival was 94% at 2
      yrs. Pre-capillary PH of mild haemodynamic severity may occur in patients with
      LAM, even with mild pulmonary function impairment. PAH therapy might improve the
      haemodynamics in PH associated with LAM.

PMID- 22362862
TI  - Cost and cost-effectiveness of multidrug-resistant tuberculosis treatment in
      Estonia and Russia.
AB  - Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant
      tuberculosis (MDR-TB) is limited, and no published data are available from former
      Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated
      the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk
      Oblast), comparing cohorts enrolled on treatment according to World Health
      Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous
      years. Costs were assessed from a health system perspective in 2003 US$; effects
      were measured as cures, deaths averted and disability-adjusted life-years (DALYs)
      averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in
      Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated
      of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed,
      cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient
      treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation
      accounted for 69-90% of total costs. The cost per DALY averted by treatment
      following WHO guidelines was US$579 (range US$297-US$902) in Estonia and US$429
      (range US$302-US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be
      cost-effective, but requires substantial additional investment in tuberculosis
      control in priority countries.

PMID- 22362863
TI  - Protection against Staphylococcus aureus by antibody to the polyglycerolphosphate
      backbone of heterologous lipoteichoic acid.
AB  - Type 1 lipoteichoic acid (LTA) is present in many clinically important gram
      positive bacteria, including enterococci, streptococci, and staphylococci, and
      antibodies against LTA have been shown to opsonize nonencapsulated Enterococcus
      faecalis strains. In the present study, we show that antibodies against E.
      faecalis LTA also bind to type 1 LTA from other gram-positive species and
      opsonized Staphylocccus epidermidis and Staphylcoccus aureus strains as well as
      group B streptococci. Inhibition studies using teichoic acid oligomers indicated
      that cross-reactive opsonic antibodies bind to the teichoic acid backbone.
      Passive immunization with rabbit antibodies against E. faecalis LTA promoted the
      clearance of bacteremia by E. faecalis and S. epidermidis in mice. Furthermore,
      passive protection also reduced mortality in a murine S. aureus peritonitis
      model. The effectiveness of rabbit antibody against LTA suggests that this
      conserved bacterial structure could function as a single vaccine antigen that
      targets multiple gram-positive pathogens.

PMID- 22362864
TI  - Multicohort genomewide association study reveals a new signal of protection
      against HIV-1 acquisition.
AB  - BACKGROUND: To date, only mutations in CCR5 have been shown to confer resistance
      to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only
      a small fraction of the observed variability in HIV susceptibility. METHODS: We
      performed a meta-analysis between 2 independent European genomewide association
      studies, each comparing HIV-1 seropositive cases with normal population controls
      known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs)
      associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10(-5) in
      this first stage underwent second-stage analysis in 2 independent US cohorts of
      European descent. RESULTS: After the first stage, a single highly significant
      association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition
      and was replicated in both second-stage cohorts. Across the 4 groups, the
      rs6996198-T allele was consistently associated with a significant reduced risk of
      HIV-1 infection, and the global meta-analysis reached genomewide significance:
      P(combined) = 7.76 * 10(-8). CONCLUSIONS: We provide strong evidence of
      association for a common variant with HIV-1 acquisition in populations of
      European ancestry. This protective signal against HIV-1 infection is the first
      identified outside the CCR5 nexus. First clues point to a potential functional
      role for a nearby candidate gene, CYP7B1, but this locus warrants further
      investigation.

PMID- 22362865
TI  - A genome-wide study on the perception of the odorants androstenone and
      galaxolide.
AB  - Twin pairs and their siblings rated the intensity of the odorants amyl acetate,
      androstenone, eugenol, Galaxolide, mercaptans, and rose (N = 1573). Heritability
      was established for ratings of androstenone (h (2) = 0.30) and Galaxolide (h(2) 
      = 0.34) but not for the other odorants. Genome-wide association analysis using
      2.3 million single nucleotide polymorphisms indicated that the most significant
      association was between androstenone and a region without known olfactory
      receptor genes (rs10966900, P = 1.2 * 10(-7)). A previously reported association
      between the olfactory receptor OR7D4 and the androstenone was not detected until
      we specifically typed this gene (P = 1.1 * 10(-4)). We also tested these 2
      associations in a second independent sample of subjects and replicated the
      results either fully (OR7D4, P = 0.00002) or partially (rs10966900, P = 0.010; N
      = 266). These findings suggest that 1) the perceived intensity of some but not
      all odorants is a heritable trait, 2) use of a current genome-wide marker panel
      did not detect a known olfactory genotype-phenotype association, and 3) person-to
      person differences in androstenone perception are influenced by OR7D4 genotype
      and perhaps by variants of other genes.

PMID- 22362866
TI  - Peripheral and central olfactory tuning in a moth.
AB  - Animals can be innately attracted to certain odorants. Because these attractants
      are particularly salient, they might be expected to induce relatively strong
      responses throughout the olfactory pathway, helping animals detect the most
      relevant odors but limiting flexibility to respond to other odors. Alternatively,
      specific neural wiring might link innately preferred odors to appropriate
      behaviors without a need for intensity biases. How nonpheromonal attractants are
      processed by the general olfactory system remains largely unknown. In the moth
      Manduca sexta, we studied this with a set of innately preferred host plant odors
      and other, neutral odors. Electroantennogram recordings showed that, as a
      population, olfactory receptor neurons (ORNs) did not respond with greater
      intensity to host plant odors, and further local field potential recordings
      showed that no specific amplification of signals induced by host plant odors
      occurred between the first olfactory center and the second. Moreover, when
      odorants were mutually diluted to elicit equally intense output from the ORNs,
      moths were able to learn to associate all tested odorants equally well with food
      reward. Together, these results suggest that, although nonpheromonal host plant
      odors activate broadly distributed responses, they may be linked to attractive
      behaviors mainly through specific wiring in the brain.

PMID- 22362868
TI  - What reaches the antenna? How to calibrate odor flux and ligand-receptor
      affinities.
AB  - Physiological studies on olfaction frequently ignore the airborne quantities of
      stimuli reaching the sensory organ. We used a gas chromatography-calibrated
      photoionization detector to estimate quantities released from standard Pasteur
      pipette stimulus cartridges during repeated puffing of 27 compounds and verified
      how lack of quantification could obscure olfactory sensory neuron (OSN)
      affinities. Chemical structure of the stimulus, solvent, dose, storage condition,
      puff interval, and puff number all influenced airborne quantities. A model
      including boiling point and lipophilicity, but excluding vapor pressure,
      predicted airborne quantities from stimuli in paraffin oil on filter paper. We
      recorded OSN responses of Drosophila melanogaster, Ips typographus, and Culex
      quinquefasciatus, to known quantities of airborne stimuli. These demonstrate that
      inferred OSN tuning width, ligand affinity, and classification can be confounded
      and require stimulus quantification. Additionally, proper dose-response analysis
      shows that Drosophila AB3A OSNs are not promiscuous, but highly specific for
      ethyl hexanoate, with other earlier proposed ligands 10- to 10 000-fold less
      potent. Finally, we reanalyzed published Drosophila OSN data (DoOR) and
      demonstrate substantial shifts in affinities after compensation for quantity and
      puff number. We conclude that consistent experimental protocols are necessary for
      correct OSN classification and present some simple rules that make calibration,
      even retroactively, readily possible.

PMID- 22362867
TI  - Residual chemoresponsiveness to acids in the superior laryngeal nerve in "taste
      blind" (P2X2/P2X3 double-KO) mice.
AB  - Mice lacking both the P2X2 and the P2X3 purinergic receptors (P2X-dblKO) exhibit
      loss of responses to all taste qualities in the taste nerves innervating the
      tongue. Similarly, these mice exhibit a near total loss of taste-related
      behaviors in brief access tests except for a near-normal avoidance of acidic
      stimuli. This persistent avoidance of acids despite the loss of gustatory neural
      responses to sour was postulated to be due to continued responsiveness of the
      superior laryngeal (SL) nerve. However, chemoresponses of the larynx are
      attributable both to taste buds and to free nerve endings. In order to test
      whether the SL nerve of P2X-dblKO mice remains responsive to acids but not to
      other tastants, we recorded responses from the SL nerve in wild-type (WT) and P2X
      dblKO mice. WT mice showed substantial SL responses to monosodium glutamate,
      sucrose, urea, and denatonium-all of which were essentially absent in P2X-dblKO
      animals. In contrast, the SL nerve of P2X-dblKO mice exhibited near-normal
      responses to citric acid (50 mM) although responsiveness of both the chorda
      tympani and the glossopharyngeal nerves to this stimulus were absent or greatly
      reduced. These results are consistent with the hypothesis that the residual
      avoidance of acidic solutions by P2X-dblKO mice may be attributable to the direct
      chemosensitivity of nerve fibers innervating the laryngeal epithelium and not to
      taste.

PMID- 22362869
TI  - Evaluating the cross-cultural validity of the Polish version of the Four
      Dimensional Symptom Questionnaire (4DSQ) using differential item functioning
      (DIF) analysis.
AB  - BACKGROUND: The original Dutch Four-Dimensional Symptom Questionnaire (4DSQ),
      which measures distress, depression, anxiety and somatization, has been
      translated into Polish with the aim of providing primary health care with a good
      screening instrument for the detection of the most prevalent mental health
      problems (anxiety, somatization, depression and distress). AIM: To check if the
      Polish version is cross-culturally valid so that the scores of Polish subjects
      can be compared with the scores of Dutch subjects and the Dutch cut-off points
      can be used in Polish subjects. METHOD: 4DSQ data were collected from a mixed
      sample of students and primary care attendees. The Polish data were compared with
      the 4DSQ data of a matched sample of Dutch students and primary care attendees.
      Two methods of differential item functioning (DIF) analysis, ordinal logistic
      regression and generalized Mantel-Haenszel, were used to detect items with DIF,
      and linear regression analysis was used to estimate the scale-level impact of
      DIF. RESULTS: Four items showing DIF were detected in the distress scale, one in
      the somatization scale and one in the anxiety scale. The DIF in distress caused
      Polish subjects with moderate scores to score circa 1 point less than their Dutch
      counterparts. CONCLUSIONS: The results of the DIF analyses suggest that the
      Polish 4DSQ measures the same constructs as the Dutch 4DSQ and that the Dutch
      norms can be used for the Polish subjects, except for distress: the first cut-off
      point should be one point lower.

PMID- 22362870
TI  - Release of apical dominance in potato tuber is accompanied by programmed cell
      death in the apical bud meristem.
AB  - Potato (Solanum tuberosum) tuber, a swollen underground stem, is used as a model
      system for the study of dormancy release and sprouting. Natural dormancy release,
      at room temperature, is initiated by tuber apical bud meristem (TAB-meristem)
      sprouting characterized by apical dominance (AD). Dormancy is shortened by
      treatments such as bromoethane (BE), which mimics the phenotype of dormancy
      release in cold storage by inducing early sprouting of several buds
      simultaneously. We studied the mechanisms governing TAB-meristem dominance
      release. TAB-meristem decapitation resulted in the development of increasing
      numbers of axillary buds with time in storage, suggesting the need for autonomous
      dormancy release of each bud prior to control by the apical bud. Hallmarks of
      programmed cell death (PCD) were identified in the TAB-meristems during normal
      growth, and these were more extensive when AD was lost following either extended
      cold storage or BE treatment. Hallmarks included DNA fragmentation, induced gene
      expression of vacuolar processing enzyme1 (VPE1), and elevated VPE activity. VPE1
      protein was semipurified from BE-treated apical buds, and its endogenous activity
      was fully inhibited by a cysteinyl aspartate-specific protease-1-specific
      inhibitor N-Acetyl-Tyr-Val-Ala-Asp-CHO (Ac-YVAD-CHO). Transmission electron
      microscopy further revealed PCD-related structural alterations in the TAB
      meristem of BE-treated tubers: a knob-like body in the vacuole, development of
      cytoplasmic vesicles, and budding-like nuclear segmentations. Treatment of tubers
      with BE and then VPE inhibitor induced faster growth and recovered AD in detached
      and nondetached apical buds, respectively. We hypothesize that PCD occurrence is
      associated with the weakening of tuber AD, allowing early sprouting of mature
      lateral buds.

PMID- 22362871
TI  - A revised architecture of primary cell walls based on biomechanical changes
      induced by substrate-specific endoglucanases.
AB  - Xyloglucan is widely believed to function as a tether between cellulose
      microfibrils in the primary cell wall, limiting cell enlargement by restricting
      the ability of microfibrils to separate laterally. To test the biomechanical
      predictions of this "tethered network" model, we assessed the ability of cucumber
      (Cucumis sativus) hypocotyl walls to undergo creep (long-term, irreversible
      extension) in response to three family-12 endo-beta-1,4-glucanases that can
      specifically hydrolyze xyloglucan, cellulose, or both. Xyloglucan-specific
      endoglucanase (XEG from Aspergillus aculeatus) failed to induce cell wall creep,
      whereas an endoglucanase that hydrolyzes both xyloglucan and cellulose (Cel12A
      from Hypocrea jecorina) induced a high creep rate. A cellulose-specific
      endoglucanase (CEG from Aspergillus niger) did not cause cell wall creep, either
      by itself or in combination with XEG. Tests with additional enzymes, including a
      family-5 endoglucanase, confirmed the conclusion that to cause creep,
      endoglucanases must cut both xyloglucan and cellulose. Similar results were
      obtained with measurements of elastic and plastic compliance. Both XEG and Cel12A
      hydrolyzed xyloglucan in intact walls, but Cel12A could hydrolyze a minor
      xyloglucan compartment recalcitrant to XEG digestion. Xyloglucan involvement in
      these enzyme responses was confirmed by experiments with Arabidopsis (Arabidopsis
      thaliana) hypocotyls, where Cel12A induced creep in wild-type but not in
      xyloglucan-deficient (xxt1/xxt2) walls. Our results are incompatible with the
      common depiction of xyloglucan as a load-bearing tether spanning the 20- to 40-nm
      spacing between cellulose microfibrils, but they do implicate a minor xyloglucan
      component in wall mechanics. The structurally important xyloglucan may be located
      in limited regions of tight contact between microfibrils.

PMID- 22362873
TI  - Life expectancy in hereditary cancer predisposing diseases: an observational
      study.
AB  - BACKGROUND: Neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), familial
      adenomatous polyposis (FAP), von Hippel-Lindau syndrome (VHL), and Gorlin
      syndrome (GS) are single gene diseases that predispose to early onset tumours.
      Few studies have assessed the effect of these diseases on life expectancy. This
      study's aim was to assess this effect, and to test the hypothesis that genetic
      registers increase survival. METHOD: NF1, NF2, VHL, FAP, and GS patients were
      identified through the North West Regional Genetic Register Service and the North
      West Cancer Intelligence Service. Information on benign and malignant tumours,
      and deaths were obtained. Kaplan-Meier curves were used to show actuarial
      survival rates for each disease, compared to the local population, and in
      patients diagnosed pre/post the regional genetic register. Log rank (Mantel-Cox)
      tests were used to compare survival between groups. RESULTS: Life expectancies
      were significantly reduced for all diseases investigated compared with the local
      population (80.0 years) (p=0.05). GS had the longest life expectancy at 73.4
      years, followed by NF1 at 71.5 years, NF2 at 69.0 years, FAP at 63.6 years, and
      VHL at 52.5 years. Patients diagnosed after establishment of the genetic register
      had an increase in survival compared to those diagnosed pre-1990: NF2 (14.7
      years), FAP (13.9 years), VHL (16.3 years), and GS (11.2 years). CONCLUSION: Life
      expectancy for all five diseases was less than normal, although in recent years
      this reached the level of the local population in GS. Although there have been
      improvements in all conditions which may in part be attributable to better
      targeted care through the genetic register service, more needs to be done to
      address the very poor life expectancy in VHL.

PMID- 22362875
TI  - Are measures of body habitus associated with mortality in cystic fibrosis?
AB  - BACKGROUND: Nutrition is an important component of clinical care for patients
      with cystic fibrosis. We aimed to test the hypothesis that increased BMI, height,
      and level of creatinine as a biomarker for lean muscle mass are associated with
      lower mortality and whether differences in these measures may contribute toward
      sex differences in survival in cystic fibrosis. METHODS: Using a cohort study
      design, we analyzed data from the UK Cystic Fibrosis Registry for patients who
      attended an annual assessment visit in 2007 and were followed-up until July 2009.
      RESULTS: Of 1,517 individuals, 62 died during the follow-up period. The odds of
      death were higher among patients in the lowest quintile of serum creatinine
      compared with the rest of the study population (OR, 3.28; 95% CI, 1.79-5.98).
      Increased height and higher BMI were also associated with lower risk of death.
      The higher mortality in female patients (OR, 1.48; 95% CI, 0.93-2.34) was
      reversed by adjustment using the absolute values for height, BMI, and serum
      creatinine level (adjusted OR, 0.44; 95% CI, 0.21-0.90) but not by the use of sex
      specific values for these exposure variables. CONCLUSIONS: Lower muscle mass,
      shorter stature, and a low BMI are associated with increased mortality in cystic
      fibrosis. These measures of body habitus may contribute to the sex-specific
      survival differences in individuals with cystic fibrosis.

PMID- 22362877
TI  - Structure and formation of the twisted plywood pattern of collagen fibrils in rat
      lamellar bone.
AB  - This study was designed to elucidate details of the structure and formation
      process of the alternate lamellar pattern known to exist in lamellar bone. For
      this purpose, we examined basic internal lamellae in femurs of young rats by
      transmission and scanning electron microscopy, the latter employing two different
      macerations with NaOH at concentrations of 10 and 24%. Observations after the
      maceration with 10% NaOH showed that the regular and periodic rotation of
      collagen fibrils caused an alternation between two types of lamellae: one
      consisting of transversely and nearly transversely cut fibrils, and the other
      consisting of longitudinally and nearly longitudinally cut fibrils. This finding
      confirms the consistency of the twisted plywood model. The maceration method with
      24% NaOH removed bone components other than cells, thus allowing for three
      dimensional observations of osteoblast morphology. Osteoblasts extended finger
      like processes paralleling the inner bone surface, and grouped in such a way
      that, within a group, the processes arranged in a similar direction. Transmission
      electron microscopy showed that newly deposited fibrils were arranged alongside
      these processes. For the formation of the alternating pattern, our findings
      suggest that: (1) osteoblasts control the collagen fibril arrangement through
      their finger-like process position; (2) osteoblasts behave similarly within a
      group; (3) osteoblasts move their processes synchronously and periodically to
      promote alternating different fibril orientation; and (4) this dynamic sequential
      deposition of fibrils results in the alternate lamellar (or twisted plywood)
      pattern.

PMID- 22362872
TI  - The human side of influenza.
AB  - A clear understanding of immunity in individuals infected with influenza virus is
      critical for the design of effective vaccination and treatment strategies.
      Whereas myriad studies have teased apart innate and adaptive immune responses to
      influenza infection in murine models, much less is known about human immunity as
      a result of the ethical and technical constraints of human research. Still, these
      murine studies have provided important insights into the critical correlates of
      protection and pathogenicity in human infection and helped direct the human
      studies that have been conducted. Here, we examine and review the current
      literature on immunity in humans infected with influenza virus, noting evidence
      offered by select murine studies and suggesting directions in which future
      research is most warranted.

PMID- 22362878
TI  - A Bruce effect in wild geladas.
AB  - Female rodents are known to terminate pregnancies after exposure to unfamiliar
      males ("Bruce effect"). Although laboratory support abounds, direct evidence for
      a Bruce effect under natural conditions is lacking. Here, we report a strong
      Bruce effect in a wild primate, the gelada (Theropithecus gelada). Female geladas
      terminate 80% of pregnancies in the weeks after a dominant male is replaced.
      Further, data on interbirth intervals suggest that pregnancy termination offers
      fitness benefits for females whose offspring would otherwise be susceptible to
      infanticide. Taken together, data support the hypothesis that the Bruce effect
      can be an adaptive strategy for females.

PMID- 22362879
TI  - Glucocorticoids can induce PTSD-like memory impairments in mice.
AB  - Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the
      trauma and by a memory impairment that decreases the ability to restrict fear to
      the appropriate context. Infusion of glucocorticoids in the hippocampus after
      fear conditioning induces PTSD-like memory impairments and an altered pattern of
      neural activation in the hippocampal-amygdalar circuit. Mice become unable to
      identify the context as the correct predictor of the threat and show fear
      responses to a discrete cue not predicting the threat in normal conditions. These
      data demonstrate PTSD-like memory impairments in rodents and identify a potential
      pathophysiological mechanism of this condition.

PMID- 22362880
TI  - Seroevidence for H5N1 influenza infections in humans: meta-analysis.
AB  - The prevalence of avian H5N1 influenza A infections in humans has not been
      definitively determined. Cases of H5N1 infection in humans confirmed by the World
      Health Organization (WHO) are fewer than 600 in number, with an overall case
      fatality rate of >50%. We hypothesize that the stringent criteria for
      confirmation of a human case of H5N1 by WHO do not account for a majority of
      infections but rather the select few hospitalized cases that are more likely to
      be severe and result in poor clinical outcome. Meta-analysis shows that 1 to 2%
      of more than 12,500 study participants from 20 studies had seroevidence for prior
      H5N1 infection.

PMID- 22362881
TI  - Coherent sensing of a mechanical resonator with a single-spin qubit.
AB  - Mechanical systems can be influenced by a wide variety of small forces, ranging
      from gravitational to optical, electrical, and magnetic. When mechanical
      resonators are scaled down to nanometer-scale dimensions, these forces can be
      harnessed to enable coupling to individual quantum systems. We demonstrate that
      the coherent evolution of a single electronic spin associated with a nitrogen
      vacancy center in diamond can be coupled to the motion of a magnetized mechanical
      resonator. Coherent manipulation of the spin is used to sense driven and Brownian
      motion of the resonator under ambient conditions with a precision below 6
      picometers. With future improvements, this technique could be used to detect
      mechanical zero-point fluctuations, realize strong spin-phonon coupling at a
      single quantum level, and implement quantum spin transducers.

PMID- 22362882
TI  - The role of driving energy and delocalized States for charge separation in
      organic semiconductors.
AB  - The electron-hole pair created via photon absorption in organic photoconversion
      systems must overcome the Coulomb attraction to achieve long-range charge
      separation. We show that this process is facilitated through the formation of
      excited, delocalized band states. In our experiments on organic photovoltaic
      cells, these states were accessed for a short time (<1 picosecond) via infrared
      (IR) optical excitation of electron-hole pairs bound at the heterojunction.
      Atomistic modeling showed that the IR photons promote bound charge pairs to
      delocalized band states, similar to those formed just after singlet exciton
      dissociation, which indicates that such states act as the gateway for charge
      separation. Our results suggest that charge separation in efficient organic
      photoconversion systems occurs through hot-state charge delocalization rather
      than energy-gradient-driven intermolecular hopping.

PMID- 22362883
TI  - Determination of glucosamine and carisoprodol in pharmaceutical formulations by
      LC with pre-column derivatization and UV detection.
AB  - A simple and reliable precolumn derivatization liquid chromatography method with
      ultraviolet detection has been developed and validated for the analysis of
      glucosamine (GS) in various dietary supplement formulations and raw materials.
      Additionally, the proposed method was used for analysis of carisoprodol (CR)
      found in ternary mixture with paracetamol (PR) and caffeine (CF). The linearity
      ranges were 1-100 MUg/mL for GS, 1-150 MUg/mL for CR, PR and CF. Derivatization
      was used with 1,2-naphthoquinone-4-sulphonic acid sodium salt in the presence of
      borate buffer. Chromatographic separation of GS-naphthoquinone derivative was
      achieved by using a mixture of acetonitrile and water (pH 7.3 adjusted with 0.1 M
      NaOH) in the ratio 10:90, v/v and flow-rate of 1.0 mL/min. UV detection was
      carried out at 280 nm. For PR, CF, and CR-naphthoquinone derivative, the
      chromatographic separation was achieved by using mixture of acetonitrile and 20
      mM KH(2)PO(4) (pH 3.0 adjusted with phosphoric acid) in the ratio 20:80, v/v and
      flow-rate of 1.0 mL/min. UV detection was carried out at 275 nm. The limits of
      detection were 37.2, 35.9, 30.4 and 40.0 ng/mL for GS, CR, PR and CF,
      respectively.

PMID- 22362885
TI  - Robust averaging during perceptual judgment is not optimal.

PMID- 22362884
TI  - Polymerase chain reaction-based assays for the diagnosis of invasive fungal
      infections.
AB  - Currently accepted fungal diagnostic techniques, such as culture, biopsy, and
      serology, lack rapidity and efficiency. Newer diagnostic methods, such as
      polymerase chain reaction (PCR)-based assays, have the potential to improve
      fungal diagnostics in a faster, more sensitive, and specific manner. Preliminary
      data indicate that, when PCR-based fungal diagnostic assays guide antifungal
      therapy, they may lower patient mortality and decrease unnecessary antifungal
      treatment, improving treatment-associated costs and avoiding toxicity. Moreover,
      newer PCR techniques can identify antifungal resistance DNA loci, but the
      clinical correlation between those loci and clinical failure has to be studied
      further. In addition, future studies need to focus on the implementation of PCR
      techniques in clinical decision making and on combining them with other
      diagnostic tests. A consensus on the standardization of PCR techniques, along
      with validation from large prospective studies, is necessary to allow widespread
      adoption of these assays.

PMID- 22362886
TI  - Importance of accurately measuring spatial abilities.

PMID- 22362887
TI  - Sex differences in spatial abilities: methodological problems in Hoffman et al.

PMID- 22362888
TI  - SRY (sex determining region Y)-box2 (Sox2)/poly ADP-ribose polymerase 1 (Parp1)
      complexes regulate pluripotency.
AB  - To gain insight into mechanisms controlling SRY (sex determining region Y)-box 2
      (Sox2) protein activity in mouse embryonic stem cells (ESCs), the endogenous Sox2
      gene was tagged with FLAG/Hemagglutinin (HA) sequences by homologous
      recombination. Sox2 protein complexes were purified from Sox2/FLAG/HA knockin
      ESCs, and interacting proteins were defined by mass spectrometry. One protein in
      the complex was poly ADP-ribose polymerase I (Parp1). The results presented below
      demonstrate that Parp1 regulates Sox2 protein activity. In response to fibroblast
      growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling, Parp1
      auto-poly ADP-ribosylation enhances Sox2-Parp1 interactions, and this complex
      inhibits Sox2 binding to octamer-binding transcription factor 4 (Oct4)/Sox2
      enhancers. Based on these results, we propose a unique mechanism in which FGF
      signaling fine-tunes Sox2 activity through posttranslational modification of a
      critical interacting protein, Parp1, and balances the maintenance of ESC
      pluripotency and differentiation. In addition, we demonstrate that regulation of
      Sox2 activity by Parp1 is critical for efficient generation of induced
      pluripotent stem cells.

PMID- 22362890
TI  - Serum levels of vitamin E are associated with early recurrence of atrial
      fibrillation after electric cardioversion.
AB  - BACKGROUND: Oxidative stress is suggested to play a role in favoring the
      occurrence of atrial fibrillation (AF). We analyzed whether vitamin E, a known
      antioxidant, or markers of oxidative stress are associated with AF recurrence in
      patients undergoing electric cardioversion. METHODS AND RESULTS: A total of 144
      patients (83 men; mean age, 71.1+/-5.4 years) underwent successful biphasic
      electric cardioversion of nonvalvular persistent AF. At baseline, urinary 8
      isoprostaglandin F2alpha and serum soluble NOX2-derived peptide (sNOX2-dp), high
      sensitivity C-reactive protein (hs-CRP), and vitamin E levels were measured in
      each patient. All patients underwent 3 months of clinical follow-up, including an
      office visit with ECG every week or in cases of symptom recurrence. During the
      follow-up, 94 patients maintained sinus rhythm, whereas 50 experienced AF
      recurrence. In unadjusted analysis, left atrial diameter and levels of urinary
      isoprostanes and serum sNOX2-dp and hs-CRP were significantly higher and serum
      vitamin E lower in patients with AF recurrence. In multivariable Cox analysis,
      serum vitamin E (hazard ratio, 0.734; 95% CI, 0.605-0.891; P<0.001) and, to a
      lesser extent, hs-CRP (P=0.047) remained significantly associated with AF
      recurrence. Urinary isoprostanes and serum sNOX2-dp levels were inversely
      correlated with serum vitamin E level (r=-0.626, P<0.001, and r=-0.460, P<0.001,
      respectively). CONCLUSIONS: The study shows that low serum vitamin E levels are
      associated with AF recurrence in patients who underwent cardioversion. Because
      vitamin E inversely correlated with oxidative stress, the findings reinforce the
      hypothesis of an interplay between oxidative stress and AF.

PMID- 22362889
TI  - The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide
      binding (OB)-fold structure.
AB  - Activation of p53 target genes for tumor suppression depends on the stress
      specific regulation of transcriptional coactivator complexes. Strap (stress
      responsive activator of p300) is activated upon DNA damage by ataxia
      telangiectasia mutated (ATM) and Chk2 kinases and is a key regulator of the p53
      response. In addition to antagonizing Mdm2, Strap facilitates the recruitment of
      p53 coactivators, including JMY and p300. Strap is a predicted TPR-repeat
      protein, but shows only limited sequence identity with any protein of known
      structure. To address this and to elucidate the molecular mechanism of Strap
      activity we determined the crystal structure of the full-length protein at 2.05 A
      resolution. The structure of Strap reveals an atypical six tetratricopeptide
      repeat (TPR) protein that also contains an unexpected
      oligonucleotide/oligosaccharide-binding (OB)-fold domain. This previously unseen
      domain organization provides an extended superhelical scaffold allowing for
      protein-protein as well as protein-DNA interaction. We show that both of the TPR
      and OB-fold domains localize to the chromatin of p53 target genes and exhibit
      intrinsic regulatory activity necessary for the Strap-dependent p53 response.

PMID- 22362891
TI  - Long-term mortality after transvenous lead extraction.
AB  - BACKGROUND: The number of cardiovascular implantable electronic devices has
      increased progressively and has led to an increased need for transvenous lead
      extraction (TLE). Multiple reports of TLE procedural outcomes exist; however,
      data regarding postprocedural and long-term mortality are limited. METHODS AND
      RESULTS: We performed a retrospective study of consecutive patients undergoing
      TLE at a single, high-volume center. Patient characteristics, indications, and
      outcomes were analyzed. A multivariable Cox regression model was developed to
      identify factors associated with mortality. Between January 2000 and December
      2010, 985 patients underwent 1043 TLE procedures. The cohort was 68% male, with a
      mean age of 63 years (range, 15-95 years) and a left ventricular ejection
      fraction of 40+/-17%. Indications included systemic infection (18%), pocket
      infection (32%), lead malfunction (30%), and other (device upgrade, venous
      occlusion, and advisory leads; 20%). There were no procedure-related deaths. The
      mean follow-up was 3.7 years (range, 0.1-11.3 years). Kaplan-Meier analysis
      demonstrated a cumulative mortality of 2.1% at 30 days, 4.2% at 3 months, 8.4% at
      1 year, and 46.8% at 10 years. In multivariable analysis, systemic infection
      (hazard ratio [HR], 3.52; 95% CI, 1.95-6.38; P<0.0001), local infection (HR,
      2.70; 95% CI, 1.55-4.67; P=0.0004), device system upgrade (HR, 2.14; 95% CI, 1.07
      4.25; P=0.03; indication compared with a reference group of extraction for lead
      malfunction), diabetes mellitus (HR, 1.71; 95% CI, 1.25-2.35; P=0.0009),
      increasing age (HR, 1.05; 95% CI, 1.04-1.07; P<0.0001), and serum creatinine (HR,
      1.16; 95% CI, 1.01-1.35; P=0.04) were significant correlates of increased
      mortality risk. CONCLUSIONS: Although TLE procedural mortality is exceedingly low
      at high-volume centers, postprocedural and long-term mortality remain high in
      certain patient populations, such as elderly patients and those undergoing TLE
      for infectious indications and device system upgrade. Information regarding TLE
      long-term outcomes may help guide cardiovascular implantable electronic device
      and lead management.

PMID- 22362892
TI  - Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose
      tissue of mice fed a ketone ester diet.
AB  - We measured the effects of a diet in which D-beta-hydroxybutyrate-(R)-1,3
      butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of
      carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of
      fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the
      control (Ctrl) mice were pair-fed to the KE group. Blood d-beta-hydroxybutyrate
      levels in the KE group were 3-5 times those reported with high-fat ketogenic
      diets. Voluntary food intake was reduced dose dependently with the KE diet.
      Feeding the KE diet for up to 1 mo increased the number of mitochondria and
      doubled the electron transport chain proteins, uncoupling protein 1, and
      mitochondrial biogenesis-regulating proteins in the interscapular brown adipose
      tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was
      twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were
      more than 2-fold those of the Ctrl group and were associated with increased
      sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater
      resting energy expenditure, but the total energy expenditure measured over a 24-h
      period or body weights was not different. The quantitative insulin-sensitivity
      check index was 73% higher in the KE group. These results identify KE as a
      potential antiobesity supplement.

PMID- 22362893
TI  - Thrombospondin-4 regulates fibrosis and remodeling of the myocardium in response
      to pressure overload.
AB  - Thrombospondin-4 (TSP-4) expression increases dramatically in hypertrophic and
      failing hearts in rodent models and in humans. The aim of this study was to
      address the function of TSP-4 in the heart. TSP-4-knockout (Thbs4(-/-)) and wild
      type (WT) mice were subjected to transverse aortic constriction (TAC) to increase
      left ventricle load. After 2 wk, Thbs4(-/-) mice had a significantly higher heart
      weight/body weight ratio than WT mice. The additional increase in the heart
      weight in TAC Thbs4(-/-) mice was due to increased deposition of extracellular
      matrix (ECM). The levels of interstitial collagens were higher in the knockout
      mice, but the size of cardiomyocytes and apoptosis in the myocardium was
      unaffected by TSP-4 deficiency, suggesting that increased reactive fibrosis was
      the primary cause of the higher heart weight. The increased ECM deposition in
      Thbs4(-/-) mice was accompanied by changes in functional parameters of the heart
      and decreased vessel density. The expression of inflammatory and fibrotic genes
      known to be influential in myocardial remodeling changed as a result of TSP-4
      deficiency in vivo and as a result of incubation of cells with recombinant TSP-4
      in vitro. Thus, TSP-4 is involved in regulating the adaptive responses of the
      heart to pressure overload, suggesting its important role in myocardial
      remodeling. Our study showed a direct influence of TSP-4 on heart function and to
      identify the mechanism of its effects on heart remodeling.

PMID- 22362894
TI  - Loss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis,
      resulting in spontaneous pulmonary fibrosis.
AB  - Type II alveolar epithelial (AT-II) cells produce pulmonary surfactant proteins
      that are essential for alveolar function. AT-II is a major target in lung injury,
      and ineffective repair of damaged alveolar epithelia has been postulated to cause
      pulmonary fibrosis. Previous studies have shown that tyrosine phosphatase Shp2 is
      expressed highly in the embryonic lung epithelial buds, and Shp2 activity is
      required for FGF-induced lung branching morphogenesis. To investigate in vivo
      function of pulmonary Shp2, we generated alveoli epithelia-specific Shp2-knockout
      (Shp2(Delta/Delta)) mice. Shp2(Delta/Delta) mice exhibit marked reduction in
      surfactant proteins, disorganized lamellar bodies, increased alveolar epithelial
      apoptosis, and interstitial pulmonary fibrosis without preceding inflammation.
      Mechanistically, Shp2 acts to mediate expression of thyroid transcription factor
      1 (TTF1) and ATP-binding cassette subfamily A member 3 (ABCA3). Shp2 also plays a
      central role in mediating FGF/GAB/ERK activity, required for epithelial repair
      program. Together, our results identify a novel role of tyrosine phosphatase Shp2
      in surfactant homeostasis, and deregulation of Shp2 triggers spontaneous
      pulmonary fibrosis with minimal inflammation.

PMID- 22362895
TI  - Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory
      Denk body formation.
AB  - Mallory-Denk bodies (MDBs) are hepatocyte inclusions that are associated with
      poor liver disease prognosis. The intermediate filament protein keratin 8 (K8)
      and its cross-linking by transglutaminase-2 (TG2) are essential for MDB
      formation. K8 hyperphosphorylation occurs in association with liver injury and
      MDB formation, but the link between keratin phosphorylation and MDB formation is
      unknown. We used a mutational approach to identify K8 Q70 as a residue that is
      important for K8 cross-linking to itself and other liver proteins. K8 cross
      linking is markedly enhanced on treating cells with a phosphatase inhibitor and
      decreases dramatically on K8 S74A or Q70N mutation in the presence of phosphatase
      inhibition. K8 Q70 cross-linking, in the context of synthetic peptides or intact
      proteins transfected into cells, is promoted by phosphorylation at K8 S74 or by
      an S74D substitution and is inhibited by S74A mutation. Transgenic mice that
      express K8 S74A or a K8 G62C liver disease variant that inhibits K8 S74
      phosphorylation have a markedly reduced ability to form MDBs. Our findings
      support a model in which the stress-triggered phosphorylation of K8 S74 induces
      K8 cross-linking by TG2, leading to MDB formation. These findings may extend to
      neuropathies and myopathies that are characterized by intermediate filament
      containing inclusions.

PMID- 22362896
TI  - Naturally occurring regulatory T cells: markers, mechanisms, and manipulation.
AB  - Naturally occurring CD4(+)CD25(high) forkhead box protein 3 (FOXP3)(+) regulatory
      T cells (nTregs) are key mediators of immunity, which orchestrate and maintain
      tolerance to self and foreign antigens. In the recent 1.5 decades, a multitude of
      studies have aimed to define the phenotype and function of nTregs and to assess
      their therapeutic potential for modulating immune mediated disorders such as
      autoimmunity, allergy, and episodes of transplant rejection. In this review, we
      summarize the current knowledge on the biology of nTregs. We address the exact
      definition of nTregs by specific markers and combinations thereof, which is a
      prerequisite for the state-of-the-art isolation of defined nTreg populations.
      Furthermore, we discuss the mechanism by which nTregs mediate immunosuppression
      and how this knowledge might translate into novel therapeutic modalities. With
      first clinical studies of nTreg-based therapies being finished, questions
      concerning the reliable sources of nTregs are becoming more and more eminent.
      Consequently, approaches allowing conversion of CD4(+) T cells into nTregs by
      coculture with antigen-presenting cells, cytokines, and/or pharmacological agents
      are discussed. In addition, genetic engineering approaches for the generation of
      antigen-specific nTregs are described.

PMID- 22362897
TI  - Ferritin couples iron and fatty acid metabolism.
AB  - A physiological relationship between iron, oxidative injury, and fatty acid
      metabolism exists, but transduction mechanisms are unclear. We propose that the
      iron storage protein ferritin contains fatty acid binding sites whose occupancy
      modulates iron uptake and release. Using isothermal microcalorimetry, we found
      that arachidonic acid binds ferritin specifically and with 60 MUM affinity.
      Arachidonate binding by ferritin enhanced iron mineralization, decreased iron
      release, and protected the fatty acid from oxidation. Cocrystals of arachidonic
      acid and horse spleen apoferritin diffracted to 2.18 A and revealed specific
      binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty
      acid and its double bonds from solvent but allows the arachidonate tail to
      project well into the ferrihydrite mineralization site on the ferritin L-subunit,
      a structural feature that we implicate in the effects on mineralization by
      demonstrating that the much shorter saturated fatty acid, caprylate, has no
      significant effects on mineralization. These combined effects of arachidonate
      binding by ferritin are expected to lower both intracellular free iron and free
      arachidonate, thereby providing a previously unrecognized mechanism for limiting
      lipid peroxidation, free radical damage, and proinflammatory cascades during
      times of cellular stress.

PMID- 22362898
TI  - Why are some amyloidoses systemic? Does hepatic "chaperoning at a distance"
      prevent cardiac deposition in a transgenic model of human senile systemic
      (transthyretin) amyloidosis?
AB  - In the human systemic amyloidoses caused by mutant or wild-type transthyretin
      (TTR), deposition occurs at a distance from the site of synthesis. The TTR
      synthesized and secreted by the hepatocyte circulates in plasma, then deposits in
      target tissues far from the producing cell, a pattern reproduced in mice
      transgenic for multiple copies of the human wild-type TTR gene. By 2 yr of age,
      half of the transgenic males show cardiac deposition resembling human senile
      systemic amyloidosis. However, as early as 3 mo of age, when there are no
      deposits, cardiac gene transcription differs from that of nontransgenic
      littermates, primarily in the expression of a large number of genes associated
      with inflammation and the immune response. At 24 mo, the hearts with
      histologically proven TTR deposits show expression of stress response genes,
      exuberant mitochondrial gene transcription, and increased expression of genes
      associated with apoptosis, relative to the hearts without TTR deposition. These
      24-mo-old hearts with TTR deposits also show a decrease in transcription of
      inflammatory genes relative to that in the younger transgenic mice. After 2 yr of
      expressing large amounts of human TTR, the livers of the transgenic mice without
      cardiac deposition display chaperone gene expression and evidence of an activated
      unfolded protein response, while the livers of animals with cardiac TTR
      deposition display neither, showing increased transcription of interferon
      responsive inflammatory genes and those encoding an antioxidant response. With
      time, in animals with cardiac deposition, it appears that hepatic proteostatic
      capacity is diminished, exposing the heart to a greater load of misfolded TTR
      with subsequent extracellular deposition. Hence systemic (cardiac) TTR deposition
      may be the direct result of the diminution in the distant chaperoning capacity of
      the liver related to age or long-standing exposure to misfolded TTR, or both.

PMID- 22362900
TI  - Sudden cardiac death among competitive adult athletes: a review.
AB  - Sudden cardiac death is the leading cause of mortality among young athletes with
      an incidence of 1-2 per 100,000 athletes per annum. It is described as 'an event
      that is non-traumatic, non-violent, unexpected, and resulting from sudden cardiac
      arrest within six hours of previously witnessed normal health'. Most predisposed
      athletes have no symptoms and there is no warning for the impending tragic event.
      The majority of cases are caused by an underlying structural cardiac abnormality,
      most commonly hypertrophic cardiomyopathy. More recently, the understanding of
      non-structural causes such as long QT syndrome and Brugada syndrome has grown and
      diagnostic criteria have been developed. This review presents the known
      aetiologies of sudden cardiac death among athletes and outlines their
      identification and management including implications for future sporting
      participation as laid out in the consensus documents produced by the European
      Society of Cardiology and the 36th Bethesda Conference.

PMID- 22362901
TI  - The impact of diabetes duration on left ventricular diastolic function and
      cardiovascular disease.
AB  - OBJECTIVES: The question of whether diabetes mellitus (DM) duration correlates
      with the severity of dysfunction has not been well studied. We hypothesised that
      the longer the duration of DM the worse the severity of left ventricular (LV)
      diastolic dysfunction and increased risk of cardiovascular disease (CVD).
      METHODS: We reviewed 547 diabetic patients between January 2005 and April 2010.
      Finally, 92 consecutive patients who presented with type 2 DM and who underwent
      echocardiographic assessment were enrolled according to the selection criteria.
      In all patients, ischaemic heart disease and heart failure were excluded.
      RESULTS: Diastolic parameters were significantly worsened with increasing
      duration of DM (p<0.05). In the >=7 years DM duration group (n=50), the E/Ea
      ratio increased significantly and the Ea/Aa ratio decreased significantly,
      compared with those in the <7 years DM duration group (n=42). CVD developed in 28
      patients (30.4%) during the follow-up period. However, the duration of DM showed
      less statistical correlation with the incidence of CVD (p=0.188) and other LV
      diastolic function indices did not differ significantly between groups with or
      without CVD. CONCLUSIONS: Alteration of diastolic function induced by DM worsens
      with increasing duration of DM. DM duration on echocardiographic evaluation time
      did not differ significantly between the CVD incident and the non-CVD incident
      groups. The rate of CVD development was not significantly different if the
      duration of DM was more than 7 years. Therefore, active medical care including
      echocardiography should be undertaken to prevent CVD from the point of diagnosis
      of type 2 DM.

PMID- 22362902
TI  - Treatment of vitamin D deficiency: divergence between clinical practice and
      expert advice.
AB  - BACKGROUND: Current recommendations for the treatment of vitamin D deficiency
      vary from calciferol 800 IU per day to loading doses of vitamin D followed by
      maintenance therapy of up to 2000 IU per day. OBJECTIVE: To assess the
      preparations and doses of vitamin D used to load and maintain patients with serum
      25-hydroxyvitamin D (25OHD) <25 nmol/l. METHODS: We examined all requests for
      serum 25OHD over a 12-month period, from September 2009 to 2010 in southwest
      Scotland. We wrote to all 33 general practices asking whether they usually
      started replacement therapy with a loading dose and/or recommended over-the
      counter maintenance preparations. We accessed the Emergency Care Summary for all
      patients with serum 25OHD <25 nmol/l to determine whether they had been
      prescribed maintenance therapy. RESULTS: Serum 25OHD was requested in 1162
      patients. Levels were <25 nmol/l in 282 (24%) patients, only 173 (61%) of whom
      were receiving vitamin D replacement therapy 3-15 months after diagnosis. Only
      four (1.4%) were prescribed a loading dose. One hundred and fifty-three (54%)
      were treated with cholecalciferol or ergocalciferol and 19 (7%) with alfacalcidol
      or calcitriol. The median dose of chole/ergocalciferol was 800 IU per day,
      usually in combination with 1200 mg calcium per day. CONCLUSIONS: We have shown a
      divergence between clinical practice and even the most conservative expert advice
      for vitamin D replacement therapy. Possible explanations are conflicting advice
      on treatment and difficulty obtaining suitable vitamin D preparations,
      particularly high dose vitamin D and vitamin D without calcium, in the UK.

PMID- 22362903
TI  - Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of
      atherosclerosis in xanthelasma).
AB  - PURPOSE: To evaluate the association between xanthelasma palpebrarum (XP) and
      atherosclerosis by the measurement of carotid intima media thickness (CIMT). In
      addition, the concurrent association between metabolic syndrome, dyslipidaemia
      and dyslipoproteinaemia was also assessed. STUDY DESIGN: A cross-sectional study
      was conducted from January 2008 to April 2009 involving 40 patients of XP and an
      equal number of age, sex and body mass index matched controls. All study subjects
      underwent CIMT estimation by ultrasonography and were evaluated for metabolic
      syndrome (obesity, blood pressure, blood glucose, serum lipid profile), non
      alcoholic fatty liver disease, apolipoprotein A1 and apolipoprotein B. RESULTS:
      The mean CIMT was significantly higher in XP patients as compared with controls.
      However, there was no correlation with the extent or the duration of the XP
      lesions. Prevalence of metabolic syndrome was similar in both groups while non
      alcoholic fatty liver disease was more frequent in XP patients as compared with
      controls (p=0.001). The mean serum cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol and triglyceride levels were
      similar in the two groups. However, there was significant increase in the mean
      pro-atherogenic apolipoprotein B and decrease in the anti-atherogenic
      apolipoprotein A1 levels in XP patients. CONCLUSIONS: Alteration in
      apolipoprotein levels (A1 and B) in XP patients may predispose to cutaneous and
      systemic deposition of lipids, including atherosclerosis. Therefore, XP patients
      irrespective of their lesion size or serum lipid levels should be screened using
      CIMT for detection of subclinical atherosclerosis.

PMID- 22362904
TI  - Molecular mechanisms of acid-base sensing by the kidney.
AB  - A major function of the kidney is to collaborate with the respiratory system to
      maintain systemic acid-base status within limits compatible with normal cell and
      organ function. It achieves this by regulating the excretion and recovery of
      bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons
      (mainly in the distal tubule and collecting duct). How proximal tubular cells and
      distal professional proton transporting (intercalated) cells sense and respond to
      changes in pH, bicarbonate, and CO(2) status is a question that has intrigued
      many generations of renal physiologists. Over the past few years, however, some
      candidate molecular pH sensors have been identified, including acid/alkali
      sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion
      channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase
      (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in
      taste buds, might also have similar roles to play in the kidney. Finally, the
      function of a variety of additional membrane channels and transporters is altered
      by pH variations both within and outside the cell, and the expression of several
      metabolic enzymes are altered by acid-base status in parts of the nephron. Thus,
      it is possible that a master pH sensor will never be identified. Rather, the
      kidney seems equipped with a battery of molecules that scan the epithelial cell
      environment to mount a coordinated physiologic response that maintains acid-base
      homeostasis. This review collates current knowledge on renal acid-base sensing in
      the context of a whole organ sensing and response process.

PMID- 22362905
TI  - Survival with three-times weekly in-center nocturnal versus conventional
      hemodialysis.
AB  - Whether the duration of hemodialysis treatments improves outcomes remains
      controversial. Here, we evaluated survival and clinical changes associated with
      converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center
      nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who
      initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care
      facilities during 2006 and 2007 were eligible. We used Cox models to compare risk
      for mortality during 2 years of follow-up in a 1:3 propensity score-matched
      cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis.
      Two-year mortality was 19% among nocturnal hemodialysis patients compared with
      27% among conventional patients. Nocturnal hemodialysis associated with a 25%
      reduction in the risk for death after adjustment for age, body mass index, and
      dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61-0.91, P=0.004).
      With respect to clinical features, interdialytic weight gain, albumin,
      hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas
      postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate,
      phosphorus, and white blood cell count declined (all P<0.001). In summary,
      notwithstanding the possibility of residual selection bias, conversion to
      treatment with nocturnal hemodialysis associates with favorable clinical
      features, laboratory biomarkers, and improved survival compared with propensity
      score-matched controls. The potential impact of extended treatment time on
      clinical outcomes while maintaining a three times per week hemodialysis schedule
      requires evaluation in future clinical trials.

PMID- 22362906
TI  - Survival in daily home hemodialysis and matched thrice-weekly in-center
      hemodialysis patients.
AB  - Frequent hemodialysis improves cardiovascular surrogates and quality-of-life
      indicators, but its effect on survival remains unclear. We used a matched-cohort
      design to assess relative mortality in daily home hemodialysis and thrice-weekly
      in-center hemodialysis patients between 2005 and 2008. We matched 1873 home
      hemodialysis patients with 9365 in-center patients (i.e., 1:5 ratio) selected
      from the prevalent population in the US Renal Data System database. Matching
      variables included first date of follow-up, demographic characteristics, and
      measures of disease severity. The cumulative incidence of death was 19.2% and
      21.7% in the home hemodialysis and in-center patients, respectively. In the
      intention-to-treat analysis, home hemodialysis associated with a 13% lower risk
      for all-cause mortality than in-center hemodialysis (hazard ratio [HR], 0.87; 95%
      confidence interval [95% CI], 0.78-0.97). Cause-specific mortality HRs were 0.92
      (95% CI, 0.78-1.09) for cardiovascular disease, 1.13 (95% CI, 0.84-1.53) for
      infection, 0.63 (95% CI, 0.41-0.95) for cachexia/dialysis withdrawal, 1.06 (95%
      CI, 0.81-1.37) for other specified cause, and 0.59 (95% CI, 0.44-0.79) for
      unknown cause. Findings were similar using as-treated analyses. We did not detect
      statistically significant evidence of heterogeneity of treatment effects in
      subgroup analyses. In summary, these data suggest that relative to thrice-weekly
      in-center hemodialysis, daily home hemodialysis associates with modest
      improvements in survival. Continued surveillance should strengthen inference
      about causes of mortality and determine whether treatment effects are homogeneous
      throughout the dialysis population.

PMID- 22362907
TI  - Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.
AB  - More frequent hemodialysis sessions and longer session lengths may offer improved
      phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily
      and Nocturnal Trials to examine the effects of treatment assignment on
      predialysis serum phosphorus and on prescribed dose of phosphorus binder,
      expressed relative to calcium carbonate on a weight basis. In the Daily Trial,
      with prescribed session lengths of 1.5-2.75 hours six times per week, assignment
      to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95%
      confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a
      1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose
      at month 12 compared with assignment to conventional hemodialysis. In the
      Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week,
      assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95%
      CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to
      conventional hemodialysis. Among patients assigned to the group receiving six
      sessions per week, 73% did not require phosphorus binders at month 12 compared
      with only 8% of patients assigned to sessions three times per week (P<0.001). At
      month 12, 42% of patients on nocturnal hemodialysis required the addition of
      phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis
      did not have major effects on calcium or parathyroid hormone concentrations in
      either trial. In conclusion, frequent hemodialysis facilitates control of
      hyperphosphatemia and extended session lengths could allow more liberal diets and
      freedom from phosphorus binders.

PMID- 22362908
TI  - Genetic or pharmacologic blockade of EGFR inhibits renal fibrosis.
AB  - Although enhanced activation of the EGF receptor (EGFR) associates with the
      development and progression of renal fibrosis, the mechanisms linking these
      observations are not completely understood. Here, after unilateral ureteral
      obstruction (UUO), wild-type mice exhibited sustained EGFR phosphorylation in the
      kidney and developed renal fibrosis that was more severe than the renal fibrosis
      observed in waved-2 mice, which have reduced EGFR tyrosine kinase activity. Waved
      2 mice also showed fewer renal tubular cells arrested at G2/M, reduced expression
      of alpha-smooth muscle actin (alpha-SMA), downregulation of multiple genes
      encoding profibrogenic cytokines, including TGF-beta1, and dephosphorylation of
      Smad3, STAT3, and ERK1/2. Administration of the specific EGFR inhibitor gefitinib
      recapitulated this phenotype in wild-type mice after UUO. Furthermore,
      inactivation of either EGFR or STAT3 reduced UUO-induced expression of lipocalin
      2, a molecule associated with the pathogenesis of CKD. In cultured renal
      interstitial fibroblasts, inhibition of EGFR also abrogated TGF-beta1- or serum
      induced phosphorylation of EGFR, STAT3, ERK1/2, and Smad3 as well as expression
      of alpha-SMA and extracelluar matrix proteins. Taken together, these data suggest
      that EGFR may mediate renal fibrogenesis by promoting transition of renal
      epithelial cells to a profibrotic phenotype, increased production of inflammatory
      factors, and activation of renal interstitial fibroblasts. Inhibition of EGFR may
      have therapeutic potential for fibrotic kidney disease.

PMID- 22362909
TI  - Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA
      nephropathy.
AB  - Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA
      nephropathy. The mechanisms underlying this abnormal glycosylation are not well
      understood, but reduced expression of the enzyme core 1, beta1,3
      galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput
      microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs
      of patients with IgA nephropathy compared with healthy persons. Among them, we
      observed upregulation of miR-148b, which potentially targets C1GALT1. Patients
      with IgA nephropathy exhibited lower C1GALT1 expression, which negatively
      correlated with miR-148b expression. Transfection of PBMCs from healthy persons
      with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold.
      Conversely, loss of miR-148b function in PBMCs of patients with IgA nephropathy
      increased C1GALT1 mRNA and protein levels to those observed in healthy persons.
      Moreover, we found that upregulation of miR-148b directly correlated with levels
      of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to
      confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted
      galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in
      the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain
      the aberrant glycosylation of IgA1, providing a potential pharmacologic target
      for IgA nephropathy.

PMID- 22362910
TI  - Intensive hemodialysis associates with improved survival compared with
      conventional hemodialysis.
AB  - Patients undergoing conventional maintenance hemodialysis typically receive three
      sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more
      intensive hemodialysis (>5.5 hours, three to seven times per week) has increased,
      but the effects of these regimens on survival are uncertain. We conducted a
      retrospective cohort study to examine whether intensive hemodialysis associates
      with better survival than conventional hemodialysis. We identified 420 patients
      in the International Quotidian Dialysis Registry who received intensive home
      hemodialysis in France, the United States, and Canada between January 2000 and
      August 2010. We matched 338 of these patients to 1388 patients in the Dialysis
      Outcomes and Practice Patterns Study who received in-center conventional
      hemodialysis during the same time period by country, ESRD duration, and
      propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1)
      sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the
      conventional group received three sessions per week with a mean treatment time of
      3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of
      338 patients receiving intensive hemodialysis died compared with 293 (21%) of
      1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100
      person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The
      strength and direction of the observed association between intensive hemodialysis
      and improved survival were consistent across all prespecified subgroups and
      sensitivity analyses. In conclusion, there is a strong association between
      intensive home hemodialysis and improved survival, but whether this relationship
      is causal remains unknown.

PMID- 22362912
TI  - The future of surgical assessment.

PMID- 22362911
TI  - Imaging of podocyte foot processes by fluorescence microscopy.
AB  - Visualizing podocyte foot processes requires electron microscopy, a technique
      that depends on special equipment, requires immunogold for colabeling, and does
      not take advantage of the growing number of in vivo fluorophores available. To
      address these limitations, we developed a genetic strategy to allow detailed
      visualization of single podocytes and their foot processes by conventional
      fluorescence microscopy. We generated a transgenic mouse line expressing a GFP
      Cre-ERT2 fusion protein under the control of the collagen alpha1(I) promoter with
      strong podocyte expression. Administration of submaximal tamoxifen allowed
      genetic labeling of single podocytes when crossed with a Cre-reporter line. Of
      three different reporter systems that we evaluated for the ability to reveal fine
      structural details of podocytes, bigenic Coll1alpha1GCE;Gt(ROSA)26Sor(tm9(CAG
      tdTomato)) mice allowed podocyte labeling with a strong and homogeneous reporter
      signal that was easily observed by epifluorescence. We could easily detect
      anatomic features of podocytes down to tertiary foot processes, and we were able
      to visualize and quantitate ultrastructural changes to foot processes after
      podocyte injury. In summary, using this method of genetic labeling and
      conventional fluorescence microscopy to visualize podocyte foot processes will
      complement electron microscopy and facilitate the analysis of podocytes and their
      precursors in vivo.

PMID- 22362913
TI  - L-PGD synthase: does its concentration in the optic nerve subarachnoid space
      correlate to the structural damage of the nerve in papilloedema or glaucoma?

PMID- 22362914
TI  - Evaluation of three PCR assays for the detection of fungi in patients with
      mycotic keratitis.

PMID- 22362915
TI  - Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation.
AB  - OBJECTIVE: Vascular remodelling during liver damage involves loss of healthy
      liver sinusoidal endothelial cell (LSEC) phenotype via capillarisation. Hedgehog
      (Hh) signalling regulates vascular development and increases during liver injury.
      This study therefore examined its role in capillarisation. DESIGN: Primary LSEC
      were cultured for 5 days to induce capillarisation. Pharmacological, antibody
      mediated and genetic approaches were used to manipulate Hh signalling. Effects on
      mRNA and protein expression of Hh-regulated genes and capillarisation markers
      were evaluated by quantitative reverse transcription PCR and immunoblot. Changes
      in LSEC function were assessed by migration and tube forming assay, and gain/loss
      of fenestrae was examined by electron microscopy. Mice with acute or chronic
      liver injury were treated with Hh inhibitors; effects on capillarisation were
      assessed by immunohistochemistry. RESULTS: Freshly isolated LSEC expressed Hh
      ligands, Hh receptors and Hh ligand antagonist Hhip. Capillarisation was
      accompanied by repression of Hhip and increased expression of Hh-regulated genes.
      Treatment with Hh agonist further induced expression of Hh ligands and Hh
      regulated genes, and upregulated capillarisation-associated genes; whereas Hh
      signalling antagonist or Hh ligand neutralising antibody each repressed
      expression of Hh target genes and capillarisation markers. LSEC isolated from
      Smo(loxP/loxP)   transgenic mice that had been infected with adenovirus
      expressing Cre-recombinase to delete Smoothened showed over 75% knockdown of
      Smoothened. During culture, Smoothened-deficient LSEC had inhibited Hh
      signalling, less induction of capillarisation-associated genes and retention of
      fenestrae. In mice with injured livers, inhibiting Hh signalling prevented
      capillarisation. CONCLUSIONS: LSEC produce and respond to Hh ligands, and use Hh
      signalling to regulate complex phenotypic changes that occur during
      capillarisation.

PMID- 22362917
TI  - Assessment of adverse events in medical care: lack of consistency between
      experienced teams using the global trigger tool.
AB  - BACKGROUND: Many patients are harmed as the result of healthcare. A retrospective
      structured record review is one way to identify adverse events (AEs). One such
      review approach is the global trigger tool (GTT), a consistent and well-developed
      method used to detect AEs. The GTT was originally intended to be used for
      measuring data over time within a single organisation. However, as the method
      spreads, it is likely that comparisons of GTT safety outcomes between hospitals
      will occur. OBJECTIVE: To evaluate agreement in judgement of AEs between well
      trained GTT teams from different hospitals. METHODS: Five teams from five
      hospitals of different sizes in the southeast of Sweden conducted a retrospective
      review of patient records from a random sample of 50 admissions between October
      2009 and May 2010. Inter-rater reliability between teams was assessed using
      descriptive and kappa statistics. RESULTS: The five teams identified 42 different
      AEs altogether. The number of identified AEs differed between the teams,
      corresponding to a level of AEs ranging from 27.2 to 99.7 per 1000 hospital days.
      Pair-wise agreement for detection of AEs ranged from 88% to 96%, with weighted
      kappa values between 0.26 and 0.77. Of the AEs, 29 (69%) were identified by only
      one team and not by the other four groups. Most AEs resulted in minor and
      transient harm, the most common being healthcare-associated infections. The level
      of agreement regarding the potential for prevention showed a large variation
      between the teams. CONCLUSIONS: The results do not encourage the use of the GTT
      for making comparisons between hospitals. The use of the GTT to this end would
      require substantial training to achieve better agreement across reviewer teams.

PMID- 22362916
TI  - Stromal cell-derived factor-1 overexpression induces gastric dysplasia through
      expansion of stromal myofibroblasts and epithelial progenitors.
AB  - OBJECTIVE: Stromal cell-derived factor-1 (SDF-1/CXCL12), the main ligand for
      CXCR4, is overexpressed in human cancer. This study addressed the precise
      contribution of SDF-1 to gastric carcinogenesis. DESIGN: SDF-1 transgenic mice
      were created and a Helicobacter-induced gastric cancer model was used in
      combination with H/K-ATPase-IL-1beta mice. Gastric tissue was analysed by
      histopathology and cells isolated from the stomach were analysed by molecular
      biological methods. RESULTS: Analysis of the H/K-ATPase/SDF-1 transgenic (SDF-Tg)
      mice showed that SDF-1 overexpression results in significant gastric epithelial
      hyperproliferation, mucous neck cell hyperplasia and spontaneous gastric
      dysplasia (wild-type mice 0/15 (0%) vs SDF-Tg mice 4/14 (28.6%), p=0.042, Fisher
      exact test) but has minimal effects on inflammation. SDF-Tg mice also showed a
      dramatic expansion of alpha-smooth muscle actin-positive myofibroblasts and CXCR4
      expressing gastric epithelial cells in the progenitor zone, both of which
      preceded the development of significant gastritis or dysplasia. Gremlin 1
      expressing mesenchymal stem cells, the putative precursors of myofibroblasts,
      were also increased within the dysplastic stomachs of SDF-Tg mice and showed
      chemotaxis in response to SDF-1 stimulation. SDF-1 overexpression alone resulted
      in minimal recruitment of haematopoietic cells to the gastric mucosa, although
      macrophages were increased late in the disease. When SDF-Tg mice were crossed
      with H/K-ATPase-IL-1beta mice or infected with Helicobacter felis, however, there
      were dramatic synergistic effects on recruitment of bone marrow-derived cells and
      progression to preneoplasia. CONCLUSION: Activation of the SDF-1/CXCR4 axis can
      contribute to early stages of carcinogenesis primarily through recruitment of
      stromal cells and modulation of the progenitor niche.

PMID- 22362918
TI  - A randomised, double blind, placebo controlled trial with vitamin D3 as an add on
      treatment to interferon beta-1b in patients with multiple sclerosis.
AB  - OBJECTIVES: To study the safety and efficacy of vitamin D3 as an add on therapy
      to interferon beta-1b (IFNB) in patients with multiple sclerosis (MS). METHODS: 1
      year, double blind, placebo controlled, randomised study in 66 MS patients. The
      primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of
      patients with serum levels of 25-hydroxyvitamin D (25(OH)D) >=85 nmol/l or intact
      parathyroid hormone (PTH) <=20 ng/l, and number of adverse events. Secondary
      outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual
      relapse rate, changes in the Expanded Disability Status Scale score, timed 25
      foot walk test and timed 10 foot tandem walk tests. RESULTS: Median change in BOD
      was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105).
      Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110
      (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum
      25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group
      (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286)
      and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a
      tendency to reduced disability accumulation (p=0.071) and to improved timed
      tandem walk (p=0.076). There were no significant differences in adverse events or
      in the annual relapse rate. CONCLUSION: Vitamin D3 add on treatment to IFNB
      reduces MRI disease activity in MS. TRIAL REGISTRATION NUMBER: EudraCT number
      2007-001958-99 and ClinicalTrialsGov number NCT01339676.

PMID- 22362919
TI  - Ten year survival and outcomes in a prospective cohort of new onset Chinese
      Parkinson's disease patients.
AB  - OBJECTIVE: The 10 year outcomes and impact of motor and non-motor features on
      survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were
      prospectively studied. METHOD: A cohort of new onset PD patients from 1995 to
      2002 was recruited from a regional hospital based movement disorder clinic.
      Subjects were classified into postural instability gait disorder (PIGD), tremor
      predominant type or mixed subtypes at presentation. All were evaluated yearly for
      development of sensory complaints, first significant fall, hallucinations,
      dementia, postural hypotension, speech disturbances, dysphagia and postural
      instability persisted during 'on' medication state (PIPon). Mortality and
      predictors of death were determined. RESULTS: 171 new onset PD patients were
      recruited. After a mean follow-up of 11.3+/-2.6 years, 50 (29%) patients died.
      The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%)
      developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints.
      Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101
      (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117
      (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%)
      lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI
      1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and
      PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death.
      CONCLUSIONS: 10 years into PD, a significant proportion of patients developed
      dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and
      dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

PMID- 22362920
TI  - Neurological picture. Distinctive MRI abnormalities in a man with dentatorubral
      pallidoluysian atrophy.

PMID- 22362921
TI  - Value of combined midbrain sonography, olfactory and motor function assessment in
      the differential diagnosis of early Parkinson's disease.
AB  - OBJECTIVE: Characteristic features of Parkinson's disease (PD) are asymmetric
      parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on
      transcranial ultrasound. However, each of these features has limited diagnostic
      value as they may be present, albeit less frequently, in other parkinsonian
      disorders. Here, the diagnostic sensitivity and specificity of combined
      assessment of these three features are evaluated. METHODS: 632 patients with
      parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes,
      essential tremor and major depressive disorder with motor slowing) were assessed
      on the Unified Parkinson's disease Rating Scale for motor asymmetry (right-left
      score difference >=2), the 12 item Sniffin' Sticks test (SS-12) and transcranial
      ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects
      (193 (35) women; age 65.4+/-9.6 (62.3+/-10.3) years) of whom 385 (68) had PD and
      132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to
      missing transcranial insonability. Of the validation cohort, all patients had a
      disease duration <=2 years and observers were blind to diagnoses. RESULTS: The
      optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia)
      and SN echogenic size >=0.24 cm(2) (SN hyperechogenicity). Sensitivity,
      specificity and positive predictive values for the diagnosis of PD were as
      follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia
      75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present
      96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation
      cohort: two features present 91%, 77% and 85%; three features present 49%, 98%
      and 97%. CONCLUSION: The combined assessment of motor asymmetry, hyposmia and SN
      hyperechogenicity improves diagnostic specificity and allows early diagnosis of
      PD.

PMID- 22362922
TI  - The role of state anxiety in children's memories for pain.
AB  - OBJECTIVE: To investigate the impact of experimentally manipulated state anxiety
      and the influence of anxiety-related variables on children's memories for pain.
      METHODS: A total of 110 children (60 boys) between the ages of 8 and 12 years
      were randomly assigned to complete a state anxiety induction task or a control
      task. Following experimental manipulation, children completed a laboratory pain
      task, pain ratings, and questionnaire measures of anxiety-related variables. 2
      weeks later, children provided pain ratings based on their memories of the pain
      task. RESULTS: The experimental manipulation effectively induced state anxiety;
      however, pain memories did not differ between groups. Irrespective of group
      assignment, children with higher state anxiety had more negative pain memories.
      State anxiety uniquely predicted children's pain memories over and above other
      well established factors. Anxiety sensitivity and trait anxiety were significant
      predictors of recalled pain-related fear. CONCLUSIONS: These data highlight the
      importance of anxiety in the development of children's memories for pain.

PMID- 22362923
TI  - Commentary: the patient-reported outcome measurement information system
      (PROMIS(r)) for children and youth: application to pediatric psychology.

PMID- 22362924
TI  - The prostaglandin E2 type 4 receptor participates in the response to acute
      oxidant stress in airway epithelial cells.
AB  - Oxidative stress is implicated in the pathogenesis of many inflammatory pulmonary
      diseases, including cystic fibrosis (CF). Delineating how oxidative stress
      stimulates CF transmembrane conductance regulator (CFTR) in airway epithelial
      cells is useful, both to increase the understanding of airways host defense and
      suggest therapeutic approaches to reduce the oxidant stress burden in the CF
      lung. Using the airway epithelial cell line Calu-3, we investigated the
      hypothesis that hydrogen peroxide (H2O2), which stimulates anion efflux through
      CFTR, does so via the production of prostaglandin E2 (PGE2). Using iodide efflux
      as a biochemical marker of CFTR activity and short circuit current (I(sc))
      recordings, we found that the H2O2-stimulated efflux was abolished by
      cyclooxygenase-1 inhibition and potentially also involves microsomal
      prostaglandin E synthase-1 activity, implicating a role for PGE2 production.
      Furthermore, H2O2 application resulted in a rapid release of PGE2 from Calu-3
      cells. We additionally hypothesized that the PGE2 subtype 4 (EP(4)) receptor was
      involved in mediating this response. In the presence of (4Z)-7-[(rel-1S,2S,5R)-5
      ((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic
      acid (AH23848) (which blocks the EP4 receptor), the H2O2-stimulated response was
      abolished. To investigate this finding in a polarized system, we measured the
      increase in I(sc) induced by H2O2 addition in the presence and absence of
      AH23848. H2O2 induced a robust increase in I(sc), which was significantly
      attenuated in the presence of AH23848, suggesting some role for the EP4 receptor.
      In conclusion, with H2O2 as a model oxidant stress, stimulation of CFTR seems to
      involve PGE2 production and likely EP4 receptor activation in Calu-3 airway
      epithelial cells. This mechanism would be compromised in the CF airways.

PMID- 22362925
TI  - An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing
      defects.
AB  - A significant proportion of disease-causing mutations affect precursor-mRNA
      splicing, inducing skipping of the exon from the mature transcript. Using F9 exon
      5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations
      associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular
      atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1
      small nuclear RNA (snRNA). In minigene expression systems, loading of U1 snRNA by
      complementarity to the normal or mutated donor splice sites (5'ss) corrected the
      exon skipping caused by mutations at the polypyrimidine tract of the acceptor
      splice site, at the consensus 5'ss or at exonic regulatory elements. To improve
      specificity and reduce potential off-target effects, we developed U1 snRNA
      variants targeting non-conserved intronic sequences downstream of the 5'ss. For
      each gene system, we identified an exon-specific U1 snRNA (ExSpeU1) able to
      rescue splicing impaired by the different types of mutations. Through splicing
      competent cDNA constructs, we demonstrated that the ExSpeU1-mediated splicing
      correction of several F9 mutations results in complete restoration of secreted
      functional factor IX levels. Furthermore, two ExSpeU1s for SMA improved SMN exon
      7 splicing in the chromosomal context of normal cells. We propose ExSpeU1s as a
      novel therapeutic strategy to correct, in several human disorders, different
      types of splicing mutations associated with defective exon definition.

PMID- 22362926
TI  - Obstetric outcome in singletons after in vitro fertilization with
      cryopreserved/thawed embryos.
AB  - BACKGROUND: There is increasing use of cryopreservation in IVF. This study
      compared singletons born after cryopreservation with singletons born after fresh
      IVF cycles and singletons born to women in the general population. METHODS: Data
      were collected for Swedish IVF treatments during the years 2002-2006. All
      singletons from single embryo transfer (SET) and double embryo transfer (DET)
      after cryopreserved (n = 2348) and fresh cycles (n = 8944) were included and
      cross-linked with the Swedish Medical Birth Registry and compared with all
      singletons born after spontaneous conception (n = 571 914). Main outcomes were
      preterm and very preterm birth and low and very low birthweight (VLBW). Other
      outcomes were small for gestational age, large for gestational age (LGA),
      perinatal mortality and maternal outcomes. RESULTS: Singletons from cryopreserved
      SET/DET or cryopreserved SET had increased rates of extreme preterm birth
      compared with singletons from the general population. A lower rate of LBW was
      found for cryopreserved SET/DET singletons compared with singletons from fresh
      cycles; however, a higher rate of perinatal mortality was detected. The rates of
      LGA and macrosomia were increased for cryopreserved SET/DET singletons when
      compared with those from fresh cycles and the general population. For maternal
      outcomes, a higher rate of pre-eclampsia was noted for pregnancies from
      cryopreserved cycles compared with those from fresh cycles or the general
      population, but the rate of placenta praevia was lower in pregnancies from
      cryopreserved cycles compared with those from fresh cycles. CONCLUSIONS: The
      obstetric outcome of singletons after cryopreservation was slightly poorer when
      compared with the general population. In comparison with fresh cycles, the
      outcome varied. The finding of an increased rate of LGA after cryopreservation
      requires further study.

PMID- 22362927
TI  - Periodontal disease: a potential modifiable risk factor limiting conception.
AB  - BACKGROUND: Periodontal disease (PD) is a common chronic infectious and
      inflammatory disease of the gums and its supporting tissues, associated with
      several adverse health outcomes including significant obstetric consequences. PD
      is treatable with good oral hygiene and dental care, and consequently is a
      modifiable variable that may lead to improvements in adult health. To date, there
      are no published studies describing the influence of PD on a woman's time to
      conceive (TTC). METHODS: This study formed part of the Smile study, which was a
      multi-centre randomized controlled trial of treatment for PD in mid-pregnancy. PD
      was defined as the presence of pockets >=4-mm deep at >=12 probing sites in fully
      erupted teeth. At the time of recruitment, women were asked about their TTC and
      whether they had required fertility treatment. RESULTS: Of 3737 pregnant women
      recruited to the study, information was available from 3416 spontaneous
      conceptions, including 1014 cases with PD (29.7%). Planned pregnancies accounted
      for 1956 of the 3416 pregnancies available for study. For 146 women, the TTC was
      >12 months and PD was more prevalent in this group (34.9% versus 25.7%, P =
      0.015). The mean TTC in women with PD was 7.1 months [confidence interval (CI):
      5.7-8.6] compared with 5.0 months (CI: 4.4-5.5, P = 0.019) in those without PD.
      PD was present in 23.8% of Caucasian women and 41.4% of non-Caucasian women.
      Compared with Caucasian women without PD, non-Caucasian women with PD had an
      increased likelihood of TTC >12 months [13.9% versus 6.2%, odds ratio (OR): 2.88
      (CI: 1.62-5.12), P < 0.001], but there was no difference for Caucasians with PD
      (8.6% versus 6.2%, OR: 1.15, CI: 0.74-1.79, P = 0.534). Other simultaneous
      predictors of TTC >1 year included age, BMI >25 and smoking. CONCLUSIONS: In the
      non-Caucasian population, PD was associated with an increased TTC, but whether
      this is related to PD, or some other factor also present within this population,
      should be further investigated.

PMID- 22362930
TI  - Discrimination between Mycoplasma and Acholeplasma species of bovine origin using
      digitonin disc diffusion assay, nisin disc diffusion assay, and conventional
      polymerase chain reaction.
AB  - Microbiological culture of milk samples has been used as a standard diagnosis for
      Mycoplasma mastitis. This technique is effective in isolating mollicutes that are
      Mycoplasma-like; however, isolates may be misinterpreted as Acholeplasma species,
      which are indistinguishable from Mycoplasma species by culture. A study to
      contrast the abilities of 2 culture-based tests, digitonin and nisin disc
      diffusion assays and a conventional polymerase chain reaction (PCR) technique, to
      discriminate between Mycoplasma and Acholeplasma was performed using 16S
      ribosomal RNA gene partial sequencing as the gold standard of comparison. A total
      of 288 bovine mollicute field isolates (248 from milk and 40 from other organ
      sites) and 13 reference strains were tested. Results obtained from the digitonin
      disc diffusion assay when it was performed with all field isolates were 92.7% and
      99.0% in agreement with the gold standard using 5 mm and 3 mm of zone of growth
      inhibition as thresholds, respectively. Considering only milk isolates,
      agreements between the digitonin disc diffusion assay with the gold standard were
      97.2% and 100% using 5 mm and 3 mm of zone of growth inhibition as thresholds,
      respectively. Culture identification using the nisin disc diffusion assay and the
      PCR was in a 100% agreement with the gold standard. Comparable results using
      culture-based nisin and digitonin disc diffusion assays, and PCR, to distinguish
      Mycoplasma and Acholeplasma species was found, especially for isolates from
      bovine milk.

PMID- 22362931
TI  - Aberrant E-cadherin, beta-catenin, and glial fibrillary acidic protein (GFAP)
      expression in canine choroid plexus tumors.
AB  - Expression of E-cadherin and beta-catenin has been widely studied in various
      human and canine epithelial tumors and has been correlated with
      dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are
      of epithelial origin, and the most important prognostic factor in human medicine
      is the tumor grade. Limited information is available regarding E-cadherin and
      beta-catenin expression in human CPTs, and no information is found in the
      veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus
      papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and
      the intensity and cellular staining pattern of E-cadherin and beta-catenin were
      correlated with histological features, paying special attention to grade,
      invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic
      protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found
      that loss of E-cadherin and beta-catenin expression was uncommon in canine CPTs.
      Rather, membranous expression of both molecules was increased in CPTs compared to
      normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant
      cytoplasmic or nuclear expression of both E-cadherin and beta-catenin was often
      observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None
      of these parameters were correlated with malignancy, and therefore, do not appear
      to be useful for prognostic information. Nevertheless, a panel of antibodies
      including E-cadherin and GFAP might be useful to support the diagnosis of CPTs
      and help to differentiate them from other tumors, such as ependymomas and
      metastatic epithelial tumors.

PMID- 22362932
TI  - The collection of lymphatic fluid from the bovine udder and its use for the
      detection of Mycobacterium avium subsp. paratuberculosis in the cow.
AB  - The objective of the current study was to evaluate the feasibility of lymph
      collection from the bovine udder and to investigate if the lymphatic fluid might
      be of diagnostic value in cows infected with Mycobacterium avium subsp.
      paratuberculosis (MAP), the etiologic agent of paratuberculosis. Lymph fluid
      collection was attempted from 58 cows, and the reactions of the cows as well as
      the level of difficulty of the procedure were recorded in 56 animals. Lymph
      samples (51 in total) were tested for the presence of MAP by nested polymerase
      chain reaction. Collection of the lymphatic fluid caused no or mild signs of
      discomfort in 94.6% of the cows; in 51.8% of cows, lymphatic fluid was attained
      on the first attempt, while sample collection was unsuccessful in 12.1%.
      Mycobacterium avium subsp. paratuberculosis was detected in 43.1% of all lymph
      samples. The bacterium was present in 66.7% of cows with clinical Johne's
      disease, in 42.8% of asymptomatic cows with a positive or suspicious enzyme
      linked immunosorbent assay (ELISA) result in blood, and in 38.7% of cows with a
      negative ELISA result in blood. The present study shows that the procedure was
      well tolerated by most cows and can easily be performed on farm. The current
      report of the isolation of MAP from lymph fluid suggests that the present
      approach could be used for the early detection of Johne's disease in cattle.

PMID- 22362933
TI  - Localization of Bovine papillomavirus in equine sarcoids and inflammatory skin
      conditions of horses using laser microdissection and two forms of DNA
      amplification.
AB  - Equine sarcoids are the most common tumor of horses. Bovine papillomavirus (BPV)
      has been suggested as the cause of sarcoids. Studies have shown that BPV is
      present in swabs or biopsies from nonsarcoid-bearing equine skin. Skin biopsies
      from a variety of different conditions and normal skin from horses with no
      reported history of sarcoids were examined by polymerase chain reaction (PCR) for
      the presence of BPV, which was found in all different types of skin conditions as
      well as normal skin. Forty-one out of 86 skin biopsies from horses without
      sarcoids were found to contain BPV DNA. Laser microdissection, followed by DNA
      amplification through both PCR and isothermal loop-mediated amplification, was
      performed on these 41 biopsies and on 70 additional BPV-positive sarcoid biopsies
      to localize the virus. Location of BPV DNA was different between sarcoid and
      nonsarcoid groups. Nonsarcoid skin biopsies were more likely to have BPV within
      intact or inflamed epidermis than sarcoids (P = 0.016 and P = 0.007,
      respectively). Areas of inflammation within the dermis and epidermis were more
      likely to contain BPV than in noninflamed areas (P = 0.008 and P = 0.009,
      respectively). Bovine papillomavirus was also found in the epidermis of all types
      of sarcoids examined, more frequently in occult sarcoids than in fibroblastic and
      nodular types (P = 0.03 and P = 0.01, respectively). Results suggest that BPV is
      commonly found in normal and inflamed equine skin, and it is likely an important
      predisposing factor in the development of sarcoids.

PMID- 22362934
TI  - Generation and diagnostic application of monoclonal antibodies against Seneca
      Valley virus.
AB  - Seneca Valley virus (SVV), a member of the Picornaviridae family, was implicated
      in a suspicious vesicular disease discovered in pigs from Canada in 2007. Because
      any outbreak of vesicular disease in pigs is assumed to be foot-and-mouth disease
      (FMD) until confirmed otherwise, a test for diagnosing the presence of SVV would
      be a very useful tool. To develop the diagnostic tests for SVV infection, 5
      monoclonal antibodies (mAbs) were produced from mice immunized with binary
      ethylenimine (BEI)-inactivated SVV. Using a dot blot assay, the reactivity of the
      mAbs was confirmed to be specific for SVV, not reacting with any of the other
      vesicular disease viruses tested. The mAbs demonstrated reactivity with SVV
      antigen in infected cells by an immunohistochemistry assay. An SVV-specific
      competitive enzyme-linked immunosorbent assay (cELISA) was developed using BEI
      inactivated SVV antigen and a mAb for serodiagnosis. The cELISA results were
      compared to the indirect isotype (immunoglobulin [Ig]M and IgG) ELISA and the
      virus neutralization test. All SVV experimentally inoculated pigs exhibited a
      positive SVV-specific antibody response at 6 days postinoculation, and the sera
      remained positive until the end of the experiment on day 57 (>40% inhibition)
      using the cELISA. The cELISA reflected the profile of the indirect ELISA for both
      IgM and IgG. This panel of SVV-specific mAbs is valuable for the identification
      of SVV antigen and the serological detection of SVV-specific antibodies.

PMID- 22362935
TI  - Experimental co-infection of pigs with Bovine viral diarrhea virus 1 and Porcine
      circovirus-2.
AB  - The role of Bovine viral diarrhea virus (BVDV) in the development of Porcine
      circovirus-2 (PCV-2)-associated disease (PCVAD) was investigated in 2
      experimental studies. In the first, separate groups of germ-free pigs were
      inoculated with filtered tissue homogenate (from diseased pigs) containing PCV-2b
      + BVDV-1-like virus (group 1), PCV-2a + BVDV-1-like virus (group 4), BVDV-1-like
      virus only (group 3), or PCV-2b + BVDV-1-like virus following a BVDV vaccination
      protocol (group 2). This last group was used to test if BVDV vaccination would
      prevent clinical PCVAD in this model. Many of the inoculated pigs had mild
      multisystemic inflammation consistent with classic PCVAD. One vaccinated, dually
      inoculated pig had acute respiratory distress followed by death at 21 days
      postinfection. Lesions in this pig resembled the severe form of PCVAD observed in
      the field since the fall of 2004, suggesting a role of ruminant pestiviruses
      and/or vaccination in the development of this disease. In the second study,
      cesarean-derived, colostrum-deprived pigs were inoculated with PCV-2b and a
      cytopathic strain of BVDV-1 (cpBVDV-NADL) either alone or in combination.
      Clinical signs of PCVAD were seen in a single animal inoculated only with PCV-2b.
      This pig had growth retardation followed by acute respiratory distress leading to
      death 30 days postinfection. Pulmonary lesions in this animal were similar to
      those seen in the pig that died in the first study. Infection with cpBVDV-NADL
      did not enhance PCV-2b replication or lesion formation.

PMID- 22362936
TI  - Characterization of a novel alloherpesvirus from Atlantic cod (Gadus morhua).
AB  - Alloherpesviruses affect freshwater and marine fish species. The aim of the
      current study was to characterize a novel alloherpesvirus in Atlantic cod (Gadus
      morhua). Samples were processed for histopathology, transmission electron
      microscopy (TEM), virus isolation, molecular characterization, and in situ
      hybridization (ISH). Histopathology revealed that the infection was restricted to
      the gills and that it induced cytomegaly in infected cells. By TEM, numerous
      viral particles with morphology compatible with a herpesvirus were observed
      inside the cytomegalic cells. To characterize this new agent, polymerase chain
      reaction amplified regions of the ATPase subunit of the terminase, and DNA
      polymerase genes were sequenced. Phylogenetic analysis revealed strongest
      similarity with alloherpesviruses belonging to the genus Ictalurivirus and
      Salmonivirus. The ISH showed specific labeling of nuclear inclusions in the
      cytomegalic cells. While virus isolation was unsuccessful, the results obtained
      through different diagnostic tests in the present study confirm the discovery of
      a new alloherpesvirus affecting Atlantic cod. The authors propose the formal
      species designation Gadid herpesvirus 1 (GaHV-1) to be considered for approval by
      the International Committee on the Taxonomy of Viruses.

PMID- 22362937
TI  - Evaluation of the automated hematology analyzer Sysmex XT-2000iV TM compared to
      the ADVIA (r) 2120 for its use in dogs, cats, and horses. Part II: Accuracy of
      leukocyte differential and reticulocyte count, impact of anticoagulant and sample
      aging.
AB  - The automated laser-based hematology analyzer Sysmex XT-2000iVTM provides a 5
      part differential count and specific cytograms that are of great interest for
      large veterinary laboratories. The aim of the study was to validate the Sysmex XT
      2000iV compared to the laser-based hematology analyzer ADVIA(r) 2120 and manual
      differential in dogs, cats, and horses as well as the impact of anticoagulant
      (heparin, ethylenediamine tetra-acetic acid [EDTA], and citrate) and storage at
      22 degrees C and 4 degrees C. Consecutive fresh K(3)-EDTA blood samples from 216
      cats, 314 dogs, and 174 horses were included. The impact of anticoagulant and
      sample storage was assessed in specimens obtained from an additional 9 cats, 10
      dogs, and 10 horses. Agreement between both analyzers was excellent to good
      except for monocytes and canine reticulocytes. Spearman rank correlation
      coefficients (r (s)) between Sysmex XT-2000iV and manual differential were good
      to fair and ranged from 0.91 (cat lymphocytes) to 0.44 (cat monocytes).
      Hematocrit value (Hct), mean corpuscular hemoglobin (MCH), MCH concentration
      (MCHC; all: P < 0.001), and mean corpuscular volume (MCV; P < 0.01) were higher
      in canine citrated blood compared to heparin and EDTA. In cats, lymphocytes and
      monocytes were lower in heparinized blood compared to EDTA (P < 0.05), whereas in
      horses no significant effect was seen. Regarding storage time and temperature,
      white and red blood cell counts, hemoglobin, and MCH were stable. Hct, MCV, and
      MCHC were influenced by erythrocyte swelling. Differential count remained stable
      for 24 hr (22 degrees C) and nearly 72 hr (4 degrees C) except for monocytes. The
      overall performance of the Sysmex XT-2000iV was excellent and compared favorably
      with that of the ADVIA 2120. A special strength was the excellent detection of
      feline eosinophils.

PMID- 22362938
TI  - Alpha-mannosidosis in goats caused by the swainsonine-containing plant Ipomoea
      verbascoidea.
AB  - A disease of the nervous system is reported in goats in the semiarid region of
      northeastern Brazil. Histological examination showed diffuse vacuolation of
      neurons and epithelial cells of the pancreas, thyroid, renal tubules, and liver.
      The swainsonine-containing plant Ipomoea verbascoidea was found on both farms
      where the goats originated. This plant was experimentally administered to 3
      goats, inducing clinical signs and histologic lesions similar to those observed
      in spontaneous cases. On the lectin histochemical analysis, cerebellar cells and
      pancreatic acinar cells gave positive reactions to Triticum vulgaris agglutinin
      (WGA), succinylated Triticum vulgaris agglutinin (sWGA), Lens culinaris
      agglutinin (LCA), Canavalia ensiformis agglutinin (ConA), Pisum sativum
      agglutinin (PSA), Ricinus communis agglutinin (RCA(120)), Arachis hypogaea
      agglutinin (PNA), and Phaseolus vulgaris erythroagglutinin (PHA-E) suggesting
      storage of alpha-fucose, alpha-D-mannose, alpha-D-glucose, beta-D-N-acetyl
      glucosamine, N-acetyl-galactosamine, and acetyl-neuraminic acid. This pattern of
      lectin staining partially agrees with results previously reported for poisoning
      by swainsonine-containing plants. The chemical analysis of dried leaves of I.
      verbascoidea detected swainsonine (0.017%), calystegine B(1) (0.16%), calystegine
      B(2) (0.05%), and calystegine C(1) (0.34%). It is concluded that I. verbascoidea
      causes alpha-mannosidosis in goats.

PMID- 22362939
TI  - Diagnostic investigation of porcine periweaning failure-to-thrive syndrome: lack
      of compelling evidence linking to common porcine pathogens.
AB  - Porcine periweaning failure-to-thrive syndrome (PFTS), an increasingly recognized
      syndrome in the swine industry of North America, is characterized by the anorexia
      of nursery pigs noticeable within 1 week of weaning, and progressive loss of body
      condition and lethargy during the next 1-2 weeks. Morbidity caused by PFTS is
      moderate, but case fatality is high. The etiology of PFTS is presently unknown
      and may include infectious agent(s), noninfectious factors, or both. PFTS was
      identified in a high health status farm with good management in early 2007. A
      diagnostic investigation was undertaken to identify the pathological lesions of,
      and infectious agents associated with, pigs demonstrating typical clinical signs.
      Affected (PFTS-SICK) and unaffected (PFTS-HLTHY) pigs from an affected farm, and
      unaffected pigs from 2 unaffected farms, were examined. The most prevalent
      lesions in PFTS-SICK pigs were superficial lymphocytic fundic gastritis, atrophic
      enteritis, superficial colitis, lymphocytic and neutrophilic rhinitis, mild
      nonsuppurative meningoencephalitis, and thymic atrophy. Rotavirus A and
      Betacoronavirus 1 (Porcine hemagglutinating encephalomyelitis virus) were
      identified only in PFTS-SICK pigs, but the significance of the viruses is
      uncertain because PFTS is not consistent with the typical presentation following
      infection by these pathogens. Porcine reproductive and respiratory syndrome
      virus, Porcine circovirus-2, Influenza A virus, Alphacoronavirus 1 (Transmissible
      gastroenteritis virus), Torque teno virus 1, Brachyspira hyodysenteriae, and
      Brachyspira pilosicoli were not identified in PFTS-SICK pigs. Suid herpesvirus 2
      (Porcine cytomegalovirus), Porcine enteric calicivirus, Torque teno virus 2,
      pathogenic Escherichia coli, and coccidia were detected in both PFTS-SICK and
      PFTS-HLTHY pigs. It was concluded that there is a lack of compelling evidence
      that PFTS is caused by any of these pathogens.

PMID- 22362940
TI  - Detection by hemi-nested reverse transcription polymerase chain reaction and
      genetic characterization of wild type strains of Canine distemper virus in
      suspected infected dogs.
AB  - A new highly sensitive and specific hemi-nested reverse transcription polymerase
      chain reaction (RT-PCR) assay was applied to detect nucleoprotein (NP) gene of
      Canine distemper virus (CDV) in samples collected from dogs showing respiratory,
      gastrointestinal, and neurological signs. Thirty-eight out of 86 samples were
      positive suggesting that despite the vaccination, canine distemper may still
      represent a high risk to the canine population. The 968 base pair (bp) fragments
      from the hemagglutinin (H) gene of 10 viral strains detected in positive samples
      were amplified and analyzed by restriction fragment length polymorphism (RFLP)
      using AluI and PsiI enzymes in order to differentiate among vaccine and wild-type
      CDV strains and to characterize the field viral strains. The products of the both
      enzymatic digestions allowed identification all viruses as wild strains of CDV.
      In addition, the RFLP analysis with AluI provided additional information about
      the identity level among the strains analyzed on the basis of the positions of
      the cleavage site in the nucleotide sequences of the H gene. The method could be
      a more useful and simpler method for molecular studies of CDV strains.

PMID- 22362941
TI  - c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast
      cell tumors: correlations with post-surgical prognosis.
AB  - Cutaneous mast cell tumors (MCTs) are among the most common neoplasms in dogs and
      show a highly variable biologic behavior. Histological grading, cell
      proliferation markers, and KIT immunohistochemistry are typically used to predict
      post-surgical prognosis. In the present study, c-KIT messenger RNA (mRNA)
      expression was measured in canine MCTs and its relationship with tumor grade,
      immunohistochemical staining pattern, post-surgical prognosis, and mutations was
      investigated. A significant increase of c-KIT mRNA was observed in MCTs versus
      healthy skin and surgical margins. Mutations were observed in 8.3% of cases. The
      KIT staining pattern was investigated for both grading systems. In particular,
      staining pattern III was associated with grade II (G2) and G3 MCTs, while
      staining patterns I and II were associated with G1 and G2 MCTs. Considering the 2
      tier histological grading, the high grade was mainly associated with pattern III
      (71%) while the low grade was associated with patterns II (70%) and I (28%). A
      weak association between the KIT staining pattern and outcome was also observed.
      The results obtained suggest that c-KIT mRNA is overexpressed in canine MCT,
      although the fold variations were not associated with the protein localization or
      complementary DNA mutations. These observations suggested that the 3 events were
      independent. The histological grading and the KIT staining pattern have
      prognostic value as previously published. Staining pattern I could be especially
      helpful in predicting a good prognosis of G2 MCTs. Sequence mutations were not
      necessarily suggestive of a worse prognosis, but might be useful in choosing a
      chemotherapy protocol.

PMID- 22362942
TI  - Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene
      and low frequency of the mutant allele in Border Collie dogs.
AB  - P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of
      the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting
      drug uptake into the central nervous system. Dogs homozygous for a 4-base pair
      deletion of the canine MDR1 gene show altered expression or function of P
      glycoprotein, resulting in neurotoxicosis after administration of the substrate
      drugs. In the present study, the usefulness of microchip electrophoresis for
      genotyping assays detecting this deletion mutation was evaluated. Mutagenically
      separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly
      developed and evaluated. Furthermore, a genotyping survey was carried out in a
      population of Border Collies dogs in Japan to determine the allele frequency in
      this breed. Microchip electrophoresis showed advantages in detection sensitivity
      and time saving over other modes of electrophoresis. The MS-PCR assay clearly
      discriminated all genotypes. Real-time PCR assay was most suitable for a large
      scale survey due to its high throughput and rapidity. The genotyping survey
      demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%,
      respectively, suggesting that the mutant allele frequency in Border Collies is
      markedly low compared to that in the susceptible dog breeds such as rough and
      smooth Collies.

PMID- 22362943
TI  - Development and validation of a Myxoma virus real-time polymerase chain reaction
      assay.
AB  - To aid in the rapid diagnosis of myxomatosis in rabbits, a real-time polymerase
      chain reaction (PCR) for the specific detection of Myxoma virus is described.
      Primers and probe were designed to amplify a 147-bp fragment within the Serp2
      gene. The assay was able to detect 23 copies of a synthesized oligo indicating a
      reliable sensitivity. In addition, the real-time PCR did not detect the Rabbit
      fibroma virus used in myxomatosis vaccines. The novel PCR was shown to be able to
      detect Myxoma virus in fresh and paraffin-embedded rabbit tissues originating
      from myxomatosis cases from various regions in Switzerland.

PMID- 22362944
TI  - Comparison of a TaqMan real-time polymerase chain reaction assay with a loop
      mediated isothermal amplification assay for detection of Gallid herpesvirus 1.
AB  - A TaqMan real-time polymerase chain reaction (PCR) and loop-mediated isothermal
      amplification (LAMP) assay were developed to detect Gallid herpesvirus 1 (GaHV-1,
      formerly Infectious laryngotracheitis virus). The standard curve of real-time PCR
      was established, and the sensitivity reached 10 copies/MUl. In the current study,
      the conversion between viral titer and GaHV-1 genomic copy number was
      constructed. Six primers for LAMP assay amplified target gene at 65 degrees C
      within 45 min, and the detection limit was 60 copies/MUl. The 6 primers were
      highly specific, sensitive, and reproducible for detection of GaHV-1. Although
      the sensitivity of LAMP was lower than that of real-time PCR, LAMP was faster,
      less expensive, and did not require a thermocycler. The LAMP assay would be a
      viable alternative assay in diagnostic laboratories that do not employ real-time
      PCR technology.

PMID- 22362945
TI  - Beta-hemolytic Streptococcus spp. from horses: a retrospective study (2000-2010).
AB  - The goal of this retrospective study was to have a comprehensive picture of the
      beta-hemolytic streptococci of horses including tissue/organ distributions and
      susceptibility patterns against specific antimicrobials between January 1, 2000
      and December 31, 2010. A total of 2,497 beta-hemolytic streptococci were isolated
      from 2,391 cases, of which Streptococcus equi subsp. zooepidemicus was the most
      frequent isolate (72.0%). Other species isolated were Streptococcus dysgalactia
      subsp. equisimilis (21.3%), Streptococcus equi subsp. equi (5.8%), and
      unidentified beta-hemolytic streptococci (0.9%). As expected, S. equi was mostly
      isolated from lymph node abscesses and the respiratory tract in foals and adult
      horses. Streptococcus equi subsp. zooepidemicus and S. equisimilis were mostly
      isolated from placenta, fetal tissues, and genital tract of horses; S.
      zooepidemicus and S. equisimilis were also recovered in significant numbers from
      a number of other organs including lung, liver, brain, kidney, and joints,
      indicating a much broader tissue tropism than S. equi. In addition, more than 1
      Streptococcus spp. was recovered in 106 cases, indicating the co-existence of
      these bacteria in some horses. This data also suggested that S. equisimilis is a
      major bacterial agent of horses, contrary to present knowledge. Based on Kirby
      Bauer antimicrobial susceptibility data, streptococci were found to be generally
      susceptible to cephalothin, erythromycin, nitrofurantoin, penicillin, and
      ticarcillin and clavulanate. Resistance to antimicrobials has not developed over
      the years, except for gentamicin and tetracycline against S. equisimilis.

PMID- 22362946
TI  - Differential reactivity of serum immunoglobulins from Brazilian wild mammals to
      staphylococcal A and streptococcal G proteins.
AB  - Human pathogens have evolved to infect vertebrate hosts other than human beings
      without causing symptoms of the disease, thus permitting them to complete their
      life cycle and to develop into infectious forms. The identification and
      management of infected animals are alternatives to control dissemination of the
      disease and to prevent human illness. In the current study, the potential use of
      staphylococcal A or streptococcal G proteins was evaluated with enzyme-linked
      immunosorbent assays (ELISAs) for seroepidemiological studies. Sera were
      collected from animals that were representative of 23 different Brazilian wild
      mammals. A high protein A binding rate was observed in all animals, except for
      the orders Didelphimorphia, Artiodactyla, and Rodentia, in which affinity was
      medium or low. Affinity for streptococcal G protein was higher in animals of the
      order Artiodactyla, whereas no streptococcal G protein binding was observed in
      samples obtained from felines (order Carnivora). Bacterial protein binding to
      mammalian immunoglobulins was confirmed by immunoblotting. The results suggest
      that secondary detection systems should be better investigated in ELISA protocols
      before their implementation in seroepidemiological studies involving wild
      mammals.

PMID- 22362947
TI  - Low rate of detectable in utero transmission of Mycobacterium avium subspecies
      paratuberculosis in a dairy herd with a low prevalence of Johne's disease.
AB  - In an effort to correlate the likelihood of in utero transmission of
      Mycobacterium avium subsp. paratuberculosis (MAP), the causal organism of Johne's
      disease, with the test status of the dam, tissues from neonatal calves borne to
      known test status cows were cultured for the presence of MAP. Tissues from a
      single calf borne to a test-positive cow shedding large numbers of organisms in
      the feces were positive for MAP. The detected overall transmission rate was
      approximately 2% (1/49), and the detected transmission rate in cows that were
      fecal culture positive and serum enzyme-linked immunosorbent assay suspect or
      positive was approximately 4.3% (1/23).

PMID- 22362948
TI  - Detection and identification of Mycobacterium tuberculosis and Mycobacterium
      bovis from clinical species using DNA microarrays.
AB  - The objectives of the current study were to evaluate the use of DNA microarray
      for the rapid and direct detection of Mycobacterium tuberculosis and
      Mycobacterium bovis in bovine milk, blood, and pharyngeal swab samples, and to
      compare the use of DNA microarrays with current molecular detection techniques.
      The present study describes a microarray assay based on mtp40 and pncA gene
      sequences, which can be used to detect M. tuberculosis and M. bovis species. Each
      probe was spotted onto a silylated glass slide with an arrayer and used for
      hybridization with fluorescently labeled DNA derived from amplified DNA samples.
      The detection limit for mycobacterial DNA using this DNA microarray method was 50
      fg (5 tubercle bacilli). Mycobacterium tuberculosis and/or M. bovis was detected
      in 7.1% (24/336) of the cattle specimens using the DNA microarray compared to
      6.0% (20/336) using culture methods. Mixed infections were detected in 3 animals
      using the DNA microarray method, whereas the mixed infections were detected in 2
      animals using either culture or polymerase chain reaction methods. The use of
      ancillary in vitro tests alongside the DNA microarray enhanced the detection of
      cattle infected with M. tuberculosis and/or M. bovis and reduced the number of
      false-positive animals that would be culled. More species may be easily added to
      this system, and supplementary probes can be added to increase the simultaneous
      detection power.

PMID- 22362949
TI  - Rapid detection of Betacoronavirus 1 from clinical fecal specimens by a novel
      reverse transcription loop-mediated isothermal amplification assay.
AB  - Betacoronavirus 1 (BCoV-1) is an important pathogen causing diarrhea in calves.
      In the current study, a novel reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for rapid detection of BCoV-1 was successfully
      developed. The primers were designed to target the highly conserved fragment of
      BCoV-1 nucleocapsid gene. The assay displayed high specificity detecting only
      BCoV-1 with no cross reaction with other viruses. When 418 clinical samples from
      6 different geographical areas of Xinjiang province were tested by the RT-LAMP
      method, the results indicated that this test is a simple, rapid, accurate, and
      sensitive method for the detection of BCoV-1.

PMID- 22362950
TI  - Isolation and sequence-based identification of Oxyporus corticola from a dog with
      generalized lymphadenopathy.
AB  - The present case report describes isolation of the fungus Oxyporus corticola from
      multiple lymphocutaneous tissues of a Beagle dog. Until recently, this fungus had
      not been reported in the human or veterinary medical literature as a cause of
      animal disease. A single previous report also involved infection in a German
      Shepherd Dog, a breed with reported increased susceptibility to disseminated
      fungal infection and dysfunctional immune response. Isolates were non-sporulating
      and required molecular identification methods for prompt differentiation from
      other fungal pathogens. Risk factors for infection with O. corticola are unknown.

PMID- 22362951
TI  - Declines in blood lead concentrations in clinically affected and unaffected
      cattle accidentally exposed to lead.
AB  - Lead (Pb) poisoning remains a common cause of morbidity in dairy and beef cattle.
      Although Pb toxicosis is typically diagnosed in cattle with clinical signs of
      acute or subacute Pb poisoning, it has been hypothesized that subclinical chronic
      exposure of cattle to Pb, which often goes undiagnosed, poses more of a risk to
      the human consumer. There is not adequate information on Pb kinetics to determine
      when or if Pb-exposed cattle can safely enter the food chain. The objectives of
      the current study were to determine whether subclinical elevations in blood Pb
      (bPb) were present in cattle from herds where 1 or more individuals had clinical
      Pb poisoning and to determine the half-life (t(1/2)) of bPb in Pb-exposed cattle.
      Samples of blood were collected and analyzed for Pb from 126 cattle from 9 farms.
      Blood lead concentrations ranged from below the detection limit (2.50 ug/dl) to
      423.0 ug/dl. Only 11 of the 94 cattle with detectable bPb had clinical signs such
      as diarrhea, blindness, bruxism, or seizures. When possible, cattle with
      detectable bPb had serial samples taken. The mean t(1/2) calculated from 44
      serially sampled cattle was 135 days (standard deviation: 125 days, range: 3-577
      days). A source of Pb on the farm was determined for all but one herd.

PMID- 22362952
TI  - Double-outlet right ventricle and double septal defects in a Rhesus macaque
      (Macaca mulatta).
AB  - A 6-year-old male India-origin Rhesus macaque (Macaca mulatta) presented with
      thin body condition and muscular atrophy. Thoracic auscultation revealed a grade
      VI/VI pansystolic murmur bilaterally. Radiographs showed cardiomegaly with
      significant left atrial and biventricular enlargement, a dilated pulmonary
      artery, and hepatomegaly. Electrocardiogram revealed a normal sinus rhythm
      interspersed with ventricular bigeminy. Hematology showed mild polycythemia and
      prerenal azotemia. Necropsy demonstrated double-outlet right ventricle with a
      large subaortic ventricular septal defect, subpulmonary stenosis, small atrial
      septal defect, and right ventricular hypertrophy. The major histological finding
      was severe chronic passive hepatic congestion. Double-outlet right ventricle is a
      rare congenital heart disease, both in human beings and animals.

PMID- 22362953
TI  - Atypical meningeal granular cell tumor in a dog.
AB  - A 10-year-old, female spayed Chihuahua dog was presented to the Veterinary
      Teaching Hospital at the University of Georgia for evaluation of seizures,
      abnormal mentation, and cervical pain of 2 months duration. On magnetic resonance
      imaging, there was generalized thickening of the meninges overlying the left
      cerebral hemisphere and along the falx cerebri. Despite symptomatic treatment,
      the dog remained neurologically affected. Consequently, the owners elected
      euthanasia. On gross examination, the meninges covering the left cerebral
      hemisphere were severely thickened and firmly adhered to the calvaria. On
      transverse section, the white matter of the left cerebral hemisphere was swollen,
      enlarged, and extended across the midline with resultant compression of the right
      cerebral hemisphere. Cytologic evaluation of an impression smear of the thickened
      meninges showed numerous large, spindloid to polygonal cells with abundant,
      amphophilic, vacuolated cytoplasm, present either in clusters or in individual
      cells. Histopathologic evaluation of the meninges revealed a poorly circumscribed
      and infiltrative, moderately cellular neoplasm, composed of vacuolated, spindloid
      to polygonal cells with marked anisocytosis and anisokaryosis, arranged in
      sheets, and occasionally separated by thick bands of connective tissue.
      Immunohistochemistry for vimentin revealed diffuse cytoplasmic staining of the
      neoplastic cells. Although the periodic acid-Schiff reaction was negative,
      ultrastructural findings showed numerous vesicles that were empty or that
      contained membranous or electron-dense material. Based on gross, microscopic,
      immunohistochemical, and ultrastructural changes, the meningeal neoplasm was
      diagnosed as an atypical granular cell tumor.

PMID- 22362954
TI  - Pulmonary arteriovenous malformation in two adult alpacas (Vicugna pacos).
AB  - Two cases of pulmonary vascular anomaly in unrelated adult alpacas (Vicugna
      pacos) are described. In the first case, a 9-year-old intact male alpaca
      presented at Oregon State University Veterinary Teaching Hospital with bilateral
      epistaxis and died the subsequent day following severe hemorrhage from the mouth
      and nostrils. At necropsy, a tortuous vascular lesion was identified in the right
      cranial lung lobe, associated with hemorrhage into airways. In the second case, a
      2-year-old female alpaca presented with postpartum anorexia, opisthotonus, and
      recumbency. In this second case, a similar vascular lesion was identified in the
      right cranial lung lobe but without associated hemorrhage. Histopathological
      examination of the lesion in both cases revealed numerous dilated, irregular
      blood vessels with marked variation in wall thickness within vessels, surrounded
      by foci of extramedullary hematopoiesis. Diagnoses of locally extensive pulmonary
      vascular anomalies (arteriovenous malformations) were made.

PMID- 22362955
TI  - Reports of oligodendrogliomas in three white-tailed deer (Odocoileus
      virginianus).
AB  - Central nervous system tumors are rarely reported in cervids. The current report
      describes gross and histopathologic oligodendrogliomas in 3 white-tailed deer
      (Odocoileus virginianus), and selected immunohistochemical properties of 2 deer.
      All deer were euthanized due to central nervous system signs. Grossly, masses
      were variably circumscribed, locally invasive in the brain, light grey, and soft,
      and ranged from 2 to 5 cm in diameter. Histologically, tumors were characteristic
      for oligodendroglioma. The tumors were composed primarily of oval to round cells
      with round normochromatic to hyperchromatic nuclei, a pale granular cytoplasm,
      and well-delineated cytoplasmic membrane, and variable amounts of mucinous
      material, hemorrhage, and dystrophic mineralization. Immunohistochemistry,
      performed on masses from 2 deer, had positive cytoplasmic staining for S100 and
      variable staining on glial fibrillary acidic protein (1 deer negative and the
      other with rare positivity in astrocytes within the mass). This manuscript
      includes a discussion on the significance of these findings relative to central
      nervous system tumors of cervids and oligodendrogliomas from other species.

PMID- 22362956
TI  - Malignant pheochromocytoma in a pig.
AB  - Endocrine tumors are rarely observed in pigs, and pheochromocytomas have been
      only punctually described. The current report describes a white and firm, 15-cm
      in diameter, neoplastic mass located in the adrenal gland with metastasis to
      regional lymph nodes in a 2.5-year-old sow. The masses had marked desmoplasia
      that supported a population of polygonal-to-spindle-shaped neoplastic cells
      arranged into cords and packets within a delicate fibrovascular stroma.
      Immunohistochemical staining of the tumor was positive for chromogranin and
      negative for neurofilament protein in adrenal and lymph node masses, which was
      characteristic of a malignant pheochromocytoma.

PMID- 22362957
TI  - Disseminated mycosis in a killer whale (Orcinus orca).
AB  - Hematological findings in a female killer whale (Orcinus orca) undergoing
      rehabilitation after sudden severe anorexia revealed continuing increases in
      serum lactate dehydrogenase and aspartate aminotransferase activities as well as
      fibrinogen concentration. Serologic evidence of herpesvirus infection and skin
      vesicles were detected 2 weeks into the treatment regimen of antibiotics and
      corticosteroids. The whale showed signs of improvement after treatment with anti
      herpesvirus drugs, but sudden severe anorexia reappeared, along with marked
      elevation of fibrinogen concentration that continued until the death. Postmortem
      examination revealed multiple light tan foci of necrosis in the skeletal and
      cardiac muscles, and lung consolidation. Microscopic findings indicated
      disseminated fungal granulomas in the skeletal and cardiac muscles, as well as
      myocarditis, mycotic embolic thromboarteritis of cardiac blood vessels, and
      bronchopneumonia with numerous typical Aspergillus-like fungi. Mucor-like
      structures in granulomas in the heart and skeletal muscle and Aspergillus-like
      fungi in the lungs were identified using periodic acid-Schiff, Gomori methenamine
      silver stain, and immunohistochemistry. The present case involves dual infection
      with Mucor and Aspergillus species in a killer whale with concurrent herpesvirus.

PMID- 22362958
TI  - Alloimmune neonatal neutropenia and neonatal isoerythrolysis in a Thoroughbred
      colt.
AB  - A 3-day-old Thoroughbred colt was originally presented for treatment of neonatal
      isoerythrolysis, which was treated with a blood transfusion. However, persistent
      neutropenia was observed despite the absence of detectable infection.
      Subsequently, a granulocyte agglutination test was performed by incubating the
      colt's neutrophils with the mare's serum; results were positive, leading to a
      clinical diagnosis of alloimmune neonatal neutropenia. The diagnosis was further
      supported via flow cytometric analysis. The colt was hospitalized and treated
      prophylactically with antimicrobials and 4 separate doses of recombinant human
      granulocyte colony-stimulating factor (rhG-CSF; 1.4-3.5 ug/kg, subcutaneously) in
      attempts to maintain the neutrophil count within reference intervals over a 4
      week period. The colt's neutrophil count increased after administration of rhG
      CSF and eventually stabilized within reference intervals by day 20. The colt
      maintained normal neutrophil counts after discharge and was reportedly healthy at
      6 months of age. Alloimmune neonatal neutropenia should be considered in foals
      with persistent neutropenia in the absence of infection. Alloimmune neonatal
      neutropenia can be treated with prophylactic antimicrobials combined with rhG-CSF
      with a favorable outcome.

PMID- 22362959
TI  - Thallium toxicosis in a dog consequent to ingestion of Mycoplasma agar plates.
AB  - A 1-year-old dog ingested a mixture of blood agar and Mycoplasma agar plates. The
      Mycoplasma agar plates contained thallium acetate, which resulted in an estimated
      minimum dose of 5 mg thallium acetate/kg bodyweight. Clinical signs over the
      course of 2-3 weeks included vomiting, diarrhea, weight loss, alopecia,
      dysphonia, ataxia, paresthesia, intension tremors, megaesophagus with subsequent
      aspiration pneumonia, and several seizure episodes. The dog was treated with
      intravenous fluids and placement of a gastric feeding tube. Thallium
      concentrations in hair were 8.2 ug/g in samples taken on day 19, 16.4 ug/g in
      samples taken 3 months after exposure, 13.4 ug/g in samples taken 5 months after
      exposure, and nondetectable in samples taken 7 months after exposure. The blood
      thallium concentration was 190 ug/l on day 19 and nondetec table 3 months after
      exposure. Megaesophagus and dysphonia continued for 10 months after exposure.
      This case of thallium poisoning following ingestion of mycoplasma agar plates
      demonstrates that unusual sources of thallium still exist and suggests that
      thallium toxicosis should be included in the list of differential diagnoses in
      dogs presented with megaesophagus, especially if alopecia and other unexplained
      peripheral neuropathies are present. Hair and blood samples are useful specimens
      to reach an accurate diagnosis even if taken several weeks post exposure. The
      postexposure blood and hair thallium concentrations reported in this case are
      useful data for diagnosticians investigating dogs with potential thallium
      poisoning.

PMID- 22362960
TI  - Junctional epidermolysis bullosa in a calf.
AB  - A case of epidermolysis bullosa in a calf descendent from a Gir bull and a Gir
      crossbreed cow is reported. The calf presented with exungulation of all hooves,
      widespread erosions and crusts on the skin, and ulcers in the oral cavity.
      Histologically, the skin showed subepidermal separation with clefts occasionally
      filled with eosinophilic clear fluid, cellular debris, or neutrophils.
      Ultrastructurally, there was epidermal-dermal separation at the level of the
      lamina lucida, with the lamina densa attached to the papillary dermis. The
      hemidesmosomes were poorly defined and small. The clinical, histological, and
      ultrastructural findings are characteristic of junctional epidermolysis bullosa.

PMID- 22362961
TI  - Helcococcus ovis isolated from a goat with purulent bronchopneumonia and
      pulmonary abscesses.
AB  - The current study describes the recovery of Helcococcus ovis from an adult female
      Verata breed goat that was euthanized because of respiratory problems and
      emaciation. At necropsy, the affected animal showed a purulent bronchopneumonia
      with scattered pulmonary abscesses and fibrous pleural adhesions. A Gram
      positive, catalase-negative, coccus-shaped bacterium was isolated from the lung
      tissue and confirmed as H. ovis by 16S ribosomal RNA gene sequencing.

PMID- 22362962
TI  - Disseminated T-cell lymphoma in a bonobo (Pan paniscus).
AB  - Disseminated lymphoma was diagnosed in an 8-year-old male bonobo (Pan paniscus).
      The male bonobo presented with a 4-6 week history of dyspnea and facial swelling
      around the eyes; thoracic radiographs and computed tomography scan indicated a
      craniodorsal mediastinal soft tissue mass. Upon gross examination, there was a
      large, cream to white mass expanding the mediastinum and pericardial sac. The
      mass extended along the thoracic aorta and cranial vena cava, through the
      thoracic inlet, along and encircling the trachea, and bilaterally into the
      thyroid glands. Microscopically, neoplastic lymphocytes were present in the
      thymus, trachea, lungs, kidney, heart, and numerous other tissues.
      Immunohistochemical staining of neoplastic lymphocytes revealed diffuse
      immunoreactivity for cluster of differentiation (CD)3 indicating T-cell lymphoma.
      Routine viral screening was negative via polymerase chain reaction.

PMID- 22362963
TI  - Amanitin intoxication in two beef calves in California.
AB  - Two 2- and 3-month-old beef calves from 2 separate herds, locations, and times
      were found dead and were submitted to the veterinary diagnostic laboratory for
      diagnostic work-up. In both cases, no premonitory signs were seen by the owners.
      Histopathology revealed acute panlobular hepatic necrosis in both calves. In
      addition, calf A had copper and selenium deficiency, and calf B had oxalate
      nephrosis, and selenium and zinc deficiencies. Alpha-amanitin was detected in the
      urine from calf A, and in the liver and rumen contents from calf B using liquid
      chromatography-mass spectrometry. The cause of panlobular hepatic necrosis and
      death of both calves was determined to be amanitin toxicosis from ingestion of
      amanitin-containing mushrooms based on microscopic changes and toxicological
      analysis of tissues. In cases of sudden death in cows with histopathological
      findings of panlobular hepatic necrosis, toxicological analysis for amanitin is
      needed for a definitive diagnosis of poisoning by amanitin-containing mushrooms.

PMID- 22362965
TI  - Emergence of canine distemper virus strains with modified molecular signature and
      enhanced neuronal tropism leading to high mortality in wild carnivores.
AB  - An ongoing canine distemper epidemic was first detected in Switzerland in the
      spring of 2009. Compared to previous local canine distemper outbreaks, it was
      characterized by unusually high morbidity and mortality, rapid spread over the
      country, and susceptibility of several wild carnivore species. Here, the authors
      describe the associated pathologic changes and phylogenetic and biological
      features of a multiple highly virulent canine distemper virus (CDV) strain
      detected in and/or isolated from red foxes (Vulpes vulpes), Eurasian badgers
      (Meles meles), stone (Martes foina) and pine (Martes martes) martens, from a
      Eurasian lynx (Lynx lynx), and a domestic dog. The main lesions included
      interstitial to bronchointerstitial pneumonia and meningopolioencephalitis,
      whereas demyelination--the classic presentation of CDV infection--was observed in
      few cases only. In the brain lesions, viral inclusions were mainly in the nuclei
      of the neurons. Some significant differences in brain and lung lesions were
      observed between foxes and mustelids. Swiss CDV isolates shared together with a
      Hungarian CDV strain detected in 2004. In vitro analysis of the hemagglutinin
      protein from one of the Swiss CDV strains revealed functional and structural
      differences from that of the reference strain A75/17, with the Swiss strain
      showing increased surface expression and binding efficiency to the signaling
      lymphocyte activation molecule (SLAM). These features might be part of a novel
      molecular signature, which might have contributed to an increase in virus
      pathogenicity, partially explaining the high morbidity and mortality, the rapid
      spread, and the large host spectrum observed in this outbreak.

PMID- 22362966
TI  - Bovine viral diarrhea virus cyclically impairs long bone trabecular modeling in
      experimental persistently infected fetuses.
AB  - Persistent infection (PI) with bovine viral diarrhea virus (BVDV) has been
      associated with osteopetrosis and other long bone lesions, most commonly
      characterized as transverse zones of unmodeled metaphyseal trabeculae in fetuses
      and calves. This study was undertaken to characterize the morphogenesis of fetal
      long bone lesions. Forty-six BVDV-naive pregnant Hereford heifers of
      approximately 18 months of age were inoculated with noncytopathic BVDV type 2
      containing media or media alone on day 75 of gestation to produce PI and control
      fetuses, respectively, which were collected via cesarean section on days 82, 89,
      97, 192, and 245 of gestation. Radiographic and histomorphometric abnormalities
      were first detected on day 192, at which age PI fetal long bone metaphyses
      contained focal densities (4 of 7 fetuses) and multiple alternating transverse
      radiodense bands (3 of 7 fetuses). Day 245 fetuses were similarly affected.
      Histomorphometric analysis of proximal tibial metaphyses from day 192 fetuses
      revealed transverse zones with increased calcified cartilage core (Cg.V/BV, %)
      and trabecular bone (BV/TV, %) volumes in regions corresponding to radiodense
      bands (P < .05). Numbers of tartrate resistant acid phosphatase positive
      osteoclasts (N.Oc/BS, #/mm(2)) and bone perimeter occupied (Oc.S/BS, %) were both
      decreased (P < .05). Mineralizing surface (MS/BS, %), a measure of tissue level
      bone formation activity, was reduced in PI fetuses (P < .05). It is concluded
      that PI with BVDV induces cyclic abnormal trabecular modeling, which is secondary
      to reduced numbers of osteoclasts. The factors responsible for these temporal
      changes are unknown but may be related to the time required for osteoclast
      differentiation from precursor cells.

PMID- 22362967
TI  - "Out of confusion as the way is......." Dylan Thomas.

PMID- 22362968
TI  - The South African national health insurance: a revolution in health-care
      delivery!
AB  - A brief overview of the Green Paper on the National Health Insurance (NHI) policy
      of South Africa is presented. It describes the intention of the NHI to ensure
      equity, address the inequalities presented by the current private and public
      health system and present an ambitious plan to change the face of the South
      African health care system over the next fourteen years. It provides the context
      of the currents system that provides the case for the change. It also provides
      some detail on the structure of the proposed new Re-engineered Primary Health
      Care system as well as the future financing of this bold new health care system
      for South Africa. The challenge will be in its implementation.

PMID- 22362969
TI  - Strengthening evaluation to capture the breadth of public health practice: ideal
      vs. real.

PMID- 22362971
TI  - India's "science for all" academy.

PMID- 22362970
TI  - NICE public health guidance update.

PMID- 22362977
TI  - Avian influenza. WHO group: H5N1 papers should be published in full.

PMID- 22362978
TI  - U.S. science budget. Scientists decry cuts that would doom ExoMars missions.

PMID- 22362979
TI  - U.S. science budget. Bigger contribution to ITER erodes domestic fusion program.

PMID- 22362980
TI  - U.S. science budget. Advocates win 'exceptional' boost for Alzheimer's research.

PMID- 22362981
TI  - U.S. science budget. Kansas veterinary biosecurity lab trampled in spending plan.

PMID- 22362983
TI  - Science in India. Ad Astra, with a 'uniquely Indian flavor'.

PMID- 22362982
TI  - Science in India. India rising.

PMID- 22362984
TI  - Q&A: Manmohan Singh. India's scholar-prime minister aims for inclusive
      development.

PMID- 22362986
TI  - Science in India. Drawing a bead on India's enigmatic monsoon.

PMID- 22362985
TI  - Science in India. Crowd-sourcing drug discovery.

PMID- 22362987
TI  - Uniting church and science for conservation.

PMID- 22362988
TI  - Growing need for agriculture experts.

PMID- 22362989
TI  - Demography's role in sustainable development.

PMID- 22362991
TI  - Comment on "Levy walks evolve through interaction between movement and
      environmental complexity".
AB  - de Jager et al. (Reports, 24 June 2011, p. 1551) concluded that mussels Levy
      walk. We confronted a larger model set with these data and found that mussels do
      not Levy walk: Their movement is best described by a composite Brownian walk.
      This shows how model selection based on an impoverished set of candidate models
      can lead to incorrect inferences.

PMID- 22362993
TI  - Climate change. Preserving Montreal Protocol climate benefits by limiting HFCs.

PMID- 22362994
TI  - Evolution. Some like it hot.

PMID- 22362995
TI  - Atmospheric science. Frictional dissipation--blame it on the rain.

PMID- 22362996
TI  - Development. Cell death by glutamine repeats?

PMID- 22362997
TI  - Structural biology. How a neurotoxin survives.

PMID- 22362998
TI  - Materials science. Solving amorphous structures--two pairs beat one.

PMID- 22362999
TI  - Genetics. Mendelian puzzles.

PMID- 22363000
TI  - IBI series winner. A season for inquiry: investigating phenology in local campus
      trees.

PMID- 22363001
TI  - Disease tolerance as a defense strategy.
AB  - The immune system protects from infections primarily by detecting and eliminating
      the invading pathogens; however, the host organism can also protect itself from
      infectious diseases by reducing the negative impact of infections on host
      fitness. This ability to tolerate a pathogen's presence is a distinct host
      defense strategy, which has been largely overlooked in animal and human studies.
      Introduction of the notion of "disease tolerance" into the conceptual tool kit of
      immunology will expand our understanding of infectious diseases and host pathogen
      interactions. Analysis of disease tolerance mechanisms should provide new
      approaches for the treatment of infections and other diseases.

PMID- 22363002
TI  - Evolution of shape by multiple regulatory changes to a growth gene.
AB  - The genetic changes responsible for morphological differences between species are
      largely unidentified. Such changes can involve modifications of growth that are
      relevant to understanding evolution, development, and disease. We identified a
      gene that induces male-specific wing size and shape differences between Nasonia
      wasp species. Fine-scale mapping and in situ hybridization reveal that changes in
      at least three regions (two strictly in noncoding sequence) around the gene
      unpaired-like (upd-like) cause changes in spatial and temporal expression of upd
      like in the developing wing and corresponding changes in wing width. Upd-like
      shows homology to the Drosophila unpaired gene, a well-studied signaling protein
      that regulates cell proliferation and differentiation. Our results indicate how
      multiple changes in the regulation of upd-like are involved in microevolution of
      morphological and sex-specific differences between species.

PMID- 22363003
TI  - The local structure of amorphous silicon.
AB  - It is widely believed that the continuous random network (CRN) model represents
      the structural topology of amorphous silicon. The key evidence is that the model
      can reproduce well experimental reduced density functions (RDFs) obtained by
      diffraction. By using a combination of electron diffraction and fluctuation
      electron microscopy (FEM) variance data as experimental constraints in a
      structural relaxation procedure, we show that the CRN is not unique in matching
      the experimental RDF. We find that inhomogeneous paracrystalline structures
      containing local cubic ordering at the 10 to 20 angstrom length scale are also
      fully consistent with the RDF data. Crucially, they also matched the FEM variance
      data, unlike the CRN model. The paracrystalline model has implications for
      understanding phase transformation processes in various materials that extend
      beyond amorphous silicon.

PMID- 22363004
TI  - Satellite estimates of precipitation-induced dissipation in the atmosphere.
AB  - A substantial amount of frictional dissipation in the atmosphere occurs in the
      microphysical shear zones surrounding falling precipitation. The dissipation rate
      is computed here from recently available satellite retrieval from the Tropical
      Rainfall Measurement Missions and is found to average 1.8 watts per square meter
      between 30 degrees S and 30 degrees N. The geographical distribution of the
      precipitation-induced dissipation is closely tied to that of precipitation but
      also reveals a stronger dissipation rate for continental convection than for
      maritime convection. Because the precipitation-induced dissipation is of the same
      magnitude as the turbulent dissipation of the kinetic energy in the atmosphere,
      changes in the hydrological cycle could potentially have a direct impact on the
      amount of kinetic energy generated and dissipated by the atmospheric circulation.

PMID- 22363005
TI  - Collapse of Classic Maya civilization related to modest reduction in
      precipitation.
AB  - The disintegration of the Classic Maya civilization in the Yucatan Peninsula and
      Central America was a complex process that occurred over an approximately 200
      year interval and involved a catastrophic depopulation of the region. Although it
      is well established that the civilization collapse coincided with widespread
      episodes of drought, their nature and severity remain enigmatic. We present a
      quantitative analysis that offers a coherent interpretation of four of the most
      detailed paleoclimate records of the event. We conclude that the droughts
      occurring during the disintegration of the Maya civilization represented up to a
      40% reduction in annual precipitation, probably due to a reduction in summer
      season tropical storm frequency and intensity.

PMID- 22363006
TI  - Evolution of the earliest horses driven by climate change in the Paleocene-Eocene
      Thermal Maximum.
AB  - Body size plays a critical role in mammalian ecology and physiology. Previous
      research has shown that many mammals became smaller during the Paleocene-Eocene
      Thermal Maximum (PETM), but the timing and magnitude of that change relative to
      climate change have been unclear. A high-resolution record of continental climate
      and equid body size change shows a directional size decrease of ~30% over the
      first ~130,000 years of the PETM, followed by a ~76% increase in the recovery
      phase of the PETM. These size changes are negatively correlated with temperature
      inferred from oxygen isotopes in mammal teeth and were probably driven by shifts
      in temperature and possibly high atmospheric CO(2) concentrations. These findings
      could be important for understanding mammalian evolutionary responses to future
      global warming.

PMID- 22363007
TI  - One-time transfers of cash or capital have long-lasting effects on
      microenterprises in Sri Lanka.
AB  - Standard economic theory suggests that one-time business grants can have at most
      temporary effects, and accordingly, policies to increase incomes of the self
      employed in developing countries typically rely on sustained engagement. In
      contrast, we found long-lasting impacts from one-time grants given in a
      randomized experiment to subsistence firms. Five years after we gave $100 or $200
      to 115 of 197 male and 100 of 190 female Sri Lankan microenterprise owners, we
      found 10-percentage-point-higher enterprise survival rates, and $8-to-$12-per
      month-higher profits for male-owned businesses that received the grants. Female
      owned businesses showed no long-term (or short-term) impacts. Our follow-up
      investigation interviewed 94% of the original sample and collected survivorship
      data from the remaining 6%, demonstrating that tracking long-term outcomes is
      both feasible and worthwhile. The results suggest that one-off grants may have
      lasting impacts on some types of subsistence firms, challenging the view that
      sustained engagement is always required.

PMID- 22363008
TI  - Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a
      polyglutamine-repeat protein.
AB  - Death is a vital developmental cell fate. In Caenorhabditis elegans, programmed
      death of the linker cell, which leads gonadal elongation, proceeds independently
      of caspases and apoptotic effectors. To identify genes promoting linker-cell
      death, we performed a genome-wide RNA interference screen. We show that linker
      cell death requires the gene pqn-41, encoding an endogenous polyglutamine-repeat
      protein. pqn-41 functions cell-autonomously and is expressed at the onset of
      linker-cell death. pqn-41 expression is controlled by the mitogen-activated
      protein kinase kinase SEK-1, which functions in parallel to the zinc-finger
      protein LIN-29 to promote cellular demise. Linker-cell death is morphologically
      similar to cell death associated with normal vertebrate development and
      polyglutamine-induced neurodegeneration. Our results may therefore provide
      molecular inroads to understanding nonapoptotic cell death in metazoan
      development and disease.

PMID- 22363009
TI  - The robustness and restoration of a network of ecological networks.
AB  - Understanding species' interactions and the robustness of interaction networks to
      species loss is essential to understand the effects of species' declines and
      extinctions. In most studies, different types of networks (such as food webs,
      parasitoid webs, seed dispersal networks, and pollination networks) have been
      studied separately. We sampled such multiple networks simultaneously in an
      agroecosystem. We show that the networks varied in their robustness; networks
      including pollinators appeared to be particularly fragile. We show that, overall,
      networks did not strongly covary in their robustness, which suggests that
      ecological restoration (for example, through agri-environment schemes)
      benefitting one functional group will not inevitably benefit others. Some
      individual plant species were disproportionately well linked to many other
      species. This type of information can be used in restoration management, because
      it identifies the plant taxa that can potentially lead to disproportionate gains
      in biodiversity.

PMID- 22363010
TI  - Botulinum neurotoxin is shielded by NTNHA in an interlocked complex.
AB  - Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also
      effective medicines. Accidental BoNT poisoning often occurs through ingestion of
      Clostridium botulinum-contaminated food. Here, we present the crystal structure
      of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein
      at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides
      large and multivalent binding interfaces to protect BoNT from gastrointestinal
      degradation. Moreover, the structure highlights key residues in BoNT that
      regulate complex assembly in a pH-dependent manner. Collectively, our findings
      define the molecular mechanisms by which NTNHA shields BoNT in the hostile
      gastrointestinal environment and releases it upon entry into the circulation.
      These results will assist in the design of small molecules for inhibiting oral
      BoNT intoxication and of delivery vehicles for oral administration of biologics.

PMID- 22363011
TI  - Single-molecule fluorescence experiments determine protein folding transition
      path times.
AB  - The transition path is the tiny fraction of an equilibrium molecular trajectory
      when a transition occurs as the free-energy barrier between two states is
      crossed. It is a single-molecule property that contains all the mechanistic
      information on how a process occurs. As a step toward observing transition paths
      in protein folding, we determined the average transition-path time for a fast-
      and a slow-folding protein from a photon-by-photon analysis of fluorescence
      trajectories in single-molecule Forster resonance energy transfer experiments.
      Whereas the folding rate coefficients differ by a factor of 10,000, the
      transition-path times differ by a factor of less than 5, which shows that a fast-
      and a slow-folding protein take almost the same time to fold when folding
      actually happens. A very simple model based on energy landscape theory can
      explain this result.

PMID- 22363012
TI  - The cellular basis of GABA(B)-mediated interhemispheric inhibition.
AB  - Interhemispheric inhibition is thought to mediate cortical rivalry between the
      two hemispheres through callosal input. The long-lasting form of this inhibition
      is believed to operate via gamma-aminobutyric acid type B (GABA(B)) receptors,
      but the process is poorly understood at the cellular level. We found that the
      firing of layer 5 pyramidal neurons in rat somatosensory cortex due to
      contralateral sensory stimulation was inhibited for hundreds of milliseconds when
      paired with ipsilateral stimulation. The inhibition acted directly on apical
      dendrites via layer 1 interneurons but was silent in the absence of pyramidal
      cell firing, relying on metabotropic inhibition of active dendritic currents
      recruited during neuronal activity. The results not only reveal the
      microcircuitry underlying interhemispheric inhibition but also demonstrate the
      importance of active dendritic properties for cortical output.

PMID- 22363013
TI  - Percutaneous intervention in peripheral artery disease improves calf muscle
      phosphocreatine recovery kinetics: a pilot study.
AB  - We hypothesized that percutaneous intervention in the affected lower extremity
      artery would improve calf muscle perfusion and cellular metabolism in patients
      with claudication and peripheral artery disease (PAD) as measured by magnetic
      resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD
      (mean +/- SD: age 57 +/- 9 years; ankle-brachial index (ABI) 0.62 +/- 0.17; seven
      males) were studied 2 months before and 10 months after lower extremity
      percutaneous intervention. Calf muscle phosphocreatine recovery time constant
      (PCr) in the revascularized leg was measured by (31)P MRS immediately after
      symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured
      using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and
      treadmill test were performed. The PCr recovery time constant improved
      significantly following intervention (91 +/- 33 s to 52 +/- 34 s, p < 0.003).
      Rest ABI also improved (0.62 +/- 0.17 to 0.93 +/- 0.25, p < 0.003). There was no
      difference in MRI-measured tissue perfusion or exercise parameters, although the
      study was underpowered for these endpoints. In conclusion, in this pilot study,
      successful large vessel percutaneous intervention in patients with symptomatic
      claudication, results in improved ABI and calf muscle phosphocreatine recovery
      kinetics.

PMID- 22363014
TI  - Progression of asymptomatic peripheral artery disease over 1 year.
AB  - The pathophysiology and time course of an individual converting from asymptomatic
      peripheral artery disease (PAD) to symptomatic claudication is unclear. The
      objectives of this study were: (1) to characterize the extent of atherosclerotic
      disease in individuals with an abnormal ankle-brachial index (ABI), but without
      claudication; and over 1 year of follow-up to (2) evaluate the progression of PAD
      using ultrasound imaging, (3) determine changes in the ABI and leg pain symptoms,
      and (4) correlate PAD progression with changes in the ABI and leg symptoms. We
      hypothesized that PAD progression would be associated with the development of
      claudication and changes in the ABI, 6-minute walk distance (6-MWD), and walking
      quality of life. Individuals with a reduced ABI but without typical intermittent
      claudication noted on community screening were invited to undergo baseline and 1
      year follow-up assessment, including duplex ultrasound. The initial and repeat
      evaluations included measurement of the ABI, lower extremity duplex arterial
      mapping, and assessment of leg pain and functional status. Of the 50 people
      studied, 44 (88%) had significant atherosclerotic lesions in the lower extremity
      arteries, affecting 80 legs. A total of 33 of 50 individuals (66%) returned for
      the 1-year follow-up visit. On ultrasound examination, two of 18 normal legs
      developed PAD, and in 48 legs with PAD at baseline, 17 legs (35%) developed new
      or progressive lesions. Thirteen legs developed new claudication. Overall, there
      was no significant worsening in the ABI, 6-MWD, or the Walking Impairment
      Questionnaire (WIQ). However, legs with new lesions or lesion progression were
      significantly more likely to develop claudication, and the 13 legs (seven
      subjects) developing claudication showed a significant decline in the 6-MWD. In
      conclusion, these data indicate that a significant number of people with
      asymptomatic PAD show progression over 1 year, that such individuals are more
      likely to develop claudication, and that those developing claudication have a
      significant decrease in their 6-MWD.

PMID- 22363015
TI  - Efficacy of optimal long-term management of multiple cardiovascular risk factors
      (CVD) on walking and quality of life in patients with peripheral artery disease
      (PAD): protocol for randomized controlled trial.
AB  - Peripheral artery disease (PAD) is an understudied chronic illness most prevalent
      in elderly individuals. PAD patients experience substantial walking impairment
      due to symptoms of limb ischemia that significantly diminishes quality of life
      (QOL). Cardiovascular disease (CVD) morbidity and mortality is increased in this
      population because of aggressive atherosclerosis resulting from untreated CVD
      risk factors. Despite current national guidelines recommending intensive CVD risk
      factor management for PAD patients, untreated CVD risk factors are common.
      Interventions that bridge this gap are imperative. The Vascular Insufficiency -
      Goals for Optimal Risk Reduction (VIGOR(2)) study is a randomized controlled
      trial (RCT) that examines the effectiveness of a long-term multifactor CVD risk
      reduction program on walking and quality of life in patients with PAD. The
      purpose of this article is to provide a detailed description of the design and
      methods of VIGOR(2). Clinical Trial Registration - URL:
      http://clinicaltrials.gov/ct2/show/NCT00537225.

PMID- 22363016
TI  - Test-retest reliability of pulse amplitude tonometry measures of vascular
      endothelial function: implications for clinical trial design.
AB  - Endothelial dysfunction is an important outcome for assessing vascular health in
      intervention studies. However, reliability of the standard non-invasive method
      (flow-mediated dilation) is a significant challenge for clinical applications and
      multicenter trials. We evaluated the repeatability of pulse amplitude tonometry
      (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar
      Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests
      (mean interval = 19.5 days) under standardized conditions. PAT-derived measures
      of endothelial function (reactive hyperemia index, RHI) and arterial stiffness
      (augmentation index, AI) showed strong repeatability (intra-class correlations =
      0.74 and 0.83, respectively). To guide future research, we also analyzed sample
      size requirements for a range of effect sizes. A crossover design powered at 0.90
      requires 28 participants to detect a 15% change in RHI. Our study is the first to
      show that PAT measurements are repeatable in adults over an interval greater than
      1 week.

PMID- 22363017
TI  - Significance of high-normal serum uric acid level as a risk factor for arterial
      stiffness in healthy Korean men.
AB  - A high serum uric acid (SUA) level is a known risk factor for cardiovascular
      disease. However, little is known about the relationship between arterial
      stiffness and uric acid in healthy subjects with a normal SUA level. We assessed
      whether a high-normal uric acid level increased arterial stiffness by measuring
      brachial-ankle pulse wave velocity (ba-PWV) in healthy subjects. Among 779
      subjects who visited the health promotion center, 393 men and 234 women with
      normal SUA levels (male: 3.5-8.0 mg/dl, female: 2.5-5.4 mg/dl) were divided into
      quartiles: in men, Q1 (n = 90, 3.5-4.3 mg/dl), Q2 (n = 94, 4.4-5.1 mg/dl), Q3 (n
      = 106, 5.2-5.9 mg/dl) and Q4 (n = 103, 6.0-8.0 mg/dl); in women, Q1 (n = 57, 2.5
      3.6 mg/dl), Q2 (n = 49, 3.7-4.1 mg/dl), Q3 (n = 61, 4.2-4.6 mg/dl) and Q4 (n =
      67, 4.7-5.4 mg/dl). The mean values of ba-PWV increased gradually by SUA
      quartile. The men's SUA had an independent, positive association with ba-PWV
      after correcting for age, glucose, body mass index, blood pressure, resting heart
      rate, high-sensitivity C-reactive protein (hs-CRP), high-density lipoprotein
      (HDL)-cholesterol and triglyceride (R (2) = 0.39, adjusted R (2) = 0.37, p <
      0.001). The odds ratios (95% CI) for high ba-PWVs (> 75th percentile, 1473 cm/s)
      in men were 1.89 (0.69-5.20, Q2), 2.36 (1.10-5.08, Q3), and 2.91 (1.39-6.11, Q4),
      after adjusting for confounding factors (p < 0.001). In women, SUA showed no
      independent association with ba-PWV (p = 0.186). After adjusting for confounding
      factors, the mean ba-PWV values of Q3 (1418 cm/s) and Q4 (1421 cm/s) in men were
      higher than those of Q1 (1355 cm/s) (p < 0.05). Above the SUA level of 5.2 mg/dl,
      arterial stiffness was increased in healthy Korean men.

PMID- 22363019
TI  - PAD and claudication: thinking outside the hemodynamics box.

PMID- 22363020
TI  - The first case record of a female patient with bubonic lymphogranuloma venereum
      (LGV), serovariant L2b.
AB  - Since 2003, a lymphogranuloma venereum epidemic has been reported in The
      Netherlands and other European countries. This epidemic is caused by Chlamydia
      trachomatis serovariant L2b and has only been seen in men having sex with men.
      The authors investigated a woman presenting with a bubo in her right groin. The
      authors showed by real-time PCR that the woman was infected with C trachomatis,
      serovariant L2b. This is the first reported case study of a female patient with
      bubonic lymphogranuloma venereum caused by serovariant L2b, which was probably
      contracted via her bisexual male partner.

PMID- 22363021
TI  - The Program Science initiative: improving the planning, implementation and
      evaluation of HIV/STI prevention programs.
AB  - In this article, the authors describe the Program Science initiative in detail,
      discuss some of its recent accomplishments and explore its significance and
      timeliness in light of the HIV prevention challenges. The authors also describe
      the Program Science series being launched and present a preview of future
      articles.

PMID- 22363018
TI  - Polyunsaturated fatty acids and peripheral artery disease.
AB  - There is substantial evidence that polyunsaturated fatty acids (PUFAs) such as n
      3 and n-6 fatty acids (FAs) play an important role in prevention of
      atherosclerosis. In vitro and in vivo studies focusing on the interactions
      between monocytes and endothelial cells have explored the molecular effects of
      FAs on these interactions. Epidemiological surveys, followed by large,
      randomized, control trials have demonstrated a reduction in major cardiovascular
      events with supplementation of n-3 FAs in secondary prevention settings. The
      evidence of beneficial effects specific to patients with peripheral artery
      disease (PAD) remains elusive, and is the focus of this review.

PMID- 22363022
TI  - Using recent infection testing algorithm tests in clinical practice.
AB  - OBJECTIVES: Recent Infection Testing Algorithm (RITA) tests are used in public
      health surveillance to identify the incidence of recently acquired HIV infection.
      This can then be used to direct public health interventions and evaluate their
      effects. We aimed to outline how RITA tests may be used in clinical practice with
      individual patients, as well as highlighting the cautions needed. METHODS: The
      clinical and laboratory aspects of RITA tests have been reviewed in the paper
      together with their clinical applications. RESULTS: For individuals, RITA tests
      can help to confirm primary HIV infection and can be useful with elements of
      partner notification. However, careful evaluation of the result is required and
      it should be considered in conjunction with the clinical history and findings.
      CONCLUSIONS: There are major epidemiological and public health advantages in
      using RITA testing but there are also advantages to using the RITA test on an
      individual basis, provided that it is used appropriately.

PMID- 22363024
TI  - Biogenic carbon-enriched and pollutant depleted SRF from commercial and
      pretreated heterogeneous waste generated by NIR sensor-based sorting.
AB  - Mechanical processing using predominantly particle size and density as separation
      criteria is currently applied in the production of solid-recovered fuel or refuse
      derived fuel. It does not sufficiently allow for the optimization of the quality
      of heterogeneous solid waste for subsequent energy recovery. Material-specific
      processing, in contrast, allows the separation criterion to be linked to specific
      chemical constituents. Therefore, the technical applicability of material
      specific sorting of heterogeneous waste, in order to optimize its routing
      options, was evaluated. Two sorting steps were tested on a pilot and a large
      scale. Near infrared multiplexed sensor-based sorting devices were used (1) to
      reduce the chlorine (Cl) respectively pollutant content, in order to broaden the
      utilization options of SRF in industrial co-incineration, and (2) to increase the
      biogenic carbon (C(bio)) content, which is highly relevant in the light of the EU
      emission trading scheme on CO2. It was found that the technology is generally
      applicable for the heterogeneous waste fractions looked at, if the sensor systems
      are appropriately adjusted for the sorting task. The first sorting step allowed
      for the removal of up to 40% of the Cl freight by separating only 3 to 5% of the
      material mass. Very low Cl concentrations were achieved in the output stream to
      be used as solid-recovered fuel stream and additionally, the cadmium (Cd) and
      lead (Pb) concentration was decreased. A two- to four-fold enriched C(bio)
      content was achieved by the second sorting step. Due to lower yields in the large
      scale test further challenges need to be addressed.

PMID- 22363023
TI  - Re-evaluation of serological criteria for early syphilis treatment efficacy:
      progression to neurosyphilis despite therapy.
AB  - OBJECTIVES: To study 17 cases of secondary syphilis that progressed to
      neurosyphilis despite appropriate treatments and whose rapid plasma reagin (RPR)
      titres showed a fourfold decrease within 6 months but did not revert to negative.
      METHODS: Secondary syphilis patients with the following criteria were analysed:
      (1) RPR titres declined fourfold within 3 months after therapy, (2) patients
      denied high-risk sexual behaviours following treatment, (3) RPR titre remained
      serofast 24 months after treatment, (4) reactive cerebrospinal fluid (CSF)
      venereal disease research laboratory (VDRL) and CSF-Treponema pallidum Particle
      Agglutination Test (TPPA) and (5) HIV antibody negative. RESULTS: 14 male and
      three female patients met the criteria. 13 patients were asymptomatic. The CSF
      leucocyte count was elevated in 10 patients of whom nine also had elevated CSF
      proteins. The RPR titres following secondary syphilis treatments were >= 1:32 in
      five cases, 1:16 in four cases, 1:8 in six cases and 1:4 in two cases. Following
      treatments for neurosyphilis, four cases with neurological or psychiatric
      manifestations resolved or improved, nine cases with raised CSF-white blood cells
      returned to normal and nine of 12 cases with raised CSF-protein declined to
      normal. CONCLUSIONS: Neurosyphilis may be detected in immunocompetent patients
      despite appropriate therapy for early-stage syphilis and appropriate serological
      responses. Clinicians should consider a CSF examination in any treated patient
      with evidence of disease progression irrespective of prior treatment history and
      serological response.

PMID- 22363025
TI  - Multiple risk behaviour in adolescence.

PMID- 22363026
TI  - Policy responses to multiple risk behaviours in adolescents.
AB  - Adolescence has long been considered a period of increased risk behaviour. This
      supposition has been supported by a wealth of empirical evidence and recently,
      health risk behaviours have been identified as a key mechanism for the general
      deterioration of adolescent health relative to other age groups. Research
      regarding adolescent risk behaviour suggests that there are often strong links
      between individual risk behaviours. The mechanisms for these associations have
      been attributed to common risk and protective factors, as well as gateway effects
      stemming from increased accessibility to additional risk behaviours. This has
      important implications for policy interventions designed to reduce risk
      behaviours in adolescence. Not only does a multiple risk behaviour approach
      increase the effectiveness of individual risk behaviour policy, but it is also
      conducive to a more cohesive, coherent and efficient approach to adolescent risk
      in general. Several examples of cohesive policy responses to multiple risk
      behaviours have emerged, but generally, policy remains segregated into individual
      risk domains. With increasing evidence for the effectiveness of integrated
      approaches, multiple risk behaviours require consideration to design and
      implement effective and efficient policy responses.

PMID- 22363027
TI  - Patterns of alcohol use and multiple risk behaviour by gender during early and
      late adolescence: the ALSPAC cohort.
AB  - BACKGROUND: Adolescent risk behaviours such as smoking, alcohol use and
      antisocial behaviour are associated with increased risk of morbidity and
      mortality. Patterns of risk behaviour may vary between genders during
      adolescence. METHODS: Analysis of data from a longitudinal birth cohort to assess
      the prevalence and distribution of multiple risk behaviours by gender at age 15
      16 years with a focus on alcohol use at age 10, 13 and 15 years. RESULTS: By age
      15 years, over half of boys and girls had consumed alcohol and one-fifth had
      engaged in binge drinking with no clear difference by gender. At age 15-16 years,
      the most prevalent risk behaviours were physical inactivity (74%), antisocial and
      criminal behaviour (42%) and hazardous drinking (34%). Boys and girls engaged in
      a similar number of behaviours but antisocial and criminal behaviours, cannabis
      use and vehicle-related risk behaviours were more prevalent among boys, whilst
      tobacco smoking, self-harm and physical inactivity were more prevalent among
      girls. CONCLUSION: Multiple risk behaviour is prevalent in both genders during
      adolescence but the pattern of individual risk behaviour varies between boys and
      girls. Effective interventions at the individual, family, school, community or
      population level are needed to address gender-specific patterns of risk behaviour
      during adolescence.

PMID- 22363029
TI  - An overview of prevention of multiple risk behaviour in adolescence and young
      adulthood.
AB  - The observed clustering, and shared underlying determinants, of risk behaviours
      in young people has led to the proposition that interventions should take a
      broader approach to risk behaviour prevention. In this review we synthesized the
      evidence on 'what works' to prevent multiple risk behaviour (focusing on tobacco,
      alcohol and illicit drug use and sexual risk behaviour) for policy-makers,
      practitioners and academics. We aimed to identify promising intervention
      programmes and to give a narrative overview of the wider influences on risk
      behaviour, in order to help inform future intervention strategies and policies.
      The most promising programme approaches for reducing multiple risk behaviour
      simultaneously address multiple domains of risk and protective factors predictive
      of risk behaviour. These programmes seek to increase resilience and promote
      positive parental/family influences and/or healthy school environments supportive
      of positive social and emotional development. However, wider influences on risk
      behaviour, such as culture, media and social climate also need to be addressed
      through broader social policy change. Furthermore, the importance of positive
      experiences during transition periods of the child-youth-adult phase of the life
      course should be appropriately addressed within intervention programmes and
      broader policy change, to reduce marginalization, social exclusion and the
      vulnerability of young people during transition periods.

PMID- 22363028
TI  - Multiple health behaviours: overview and implications.
AB  - BACKGROUND: More remains unknown than known about how to optimize multiple health
      behaviour change. METHODS: After reviewing the prevalence and comorbidities among
      major chronic disease risk behaviours for adults and youth, we consider the
      origins and applicability of high-risk and population strategies to foster
      multiple health behaviour change. RESULTS: Findings indicate that health risk
      behaviours are prevalent, increase with age and co-occur as risk behaviour
      clusters or bundles. CONCLUSIONS: We conclude that both population and high-risk
      strategies for health behaviour intervention are warranted, potentially
      synergistic and need intervention design that accounts for substitute and
      complementary relationships among bundled health behaviours. To maximize positive
      public health impact, a pressing need exists for bodies of basic and
      translational science that explain health behaviour bundling. Also needed is
      applied science that elucidates the following: (1) the optimal number of
      behaviours to intervene upon; (2) how target behaviours are best selected (e.g.
      greatest health impact; patient preference or positive effect on bundled
      behaviours); (3) whether to increase healthy or decrease unhealthy behaviours;
      (4) whether to intervene on health behaviours simultaneously or sequentially and
      (5) how to achieve positive synergies across individual-, group- and population
      level intervention approaches.

PMID- 22363030
TI  - Towards a public health approach to parenting programmes for parents of
      adolescents.
AB  - BACKGROUND: Poor parenting practices have been associated with adolescent
      emotional and behavioural problems which are potentially preventable. Parenting
      interventions that are based on behavioural and social learning theories have
      been repeatedly shown to be effective. However, few evidence-based parenting
      programmes are implemented and sustained at a population level. Little research
      is available on supporting the general population of parents during the
      adolescent years. Further, a substantial research-practice gap exists regarding
      the impact of a universal approach to parenting programmes for parents of
      adolescents. METHOD: This article will first examine the effects of parenting
      practices on adolescent outcome. Afterwards, it addresses the effectiveness of
      parenting programmes for parents of adolescents. Finally, it discusses the need
      for a public health approach to parenting programmes.

PMID- 22363031
TI  - Adolescent multiple risk behaviour: an asset approach to the role of family,
      school and community.
AB  - BACKGROUND: Engagement in risk behaviours may pose a significant threat to health
      if involvement spans multiple behaviours. The asset model suggests that
      contextual aspects of young people's lives, such as factors related to family,
      school and community, serve as a protective function against health risk
      behaviours. METHODS: A risk-taking index was created from the English health
      behaviour in school-aged children study on 15 years olds, substance use and
      sexual activity. Using a multinomial regression, potential asset variables
      relating to school, family, peers, community and family affluence were tested for
      their association with levels of risk behaviours. RESULTS: Sense of neighbourhood
      belonging, strong school belonging and parental involvement in decision-making
      about leisure time were related to lower engagement in health risk behaviours. A
      weaker sense of family belonging was associated with increased risk behaviours if
      connectedness with teachers was also low. Factors related to school and community
      played a greater role in adolescent participation in health-related risk
      behaviours than family-related factors, including family affluence. CONCLUSIONS:
      Feelings of safety and belonging in the out-of-home settings of adolescents were
      positively associated with reduced risk behaviours, and indicate the importance
      of the wider community alongside parents and school as protective assets for
      health.

PMID- 22363032
TI  - A review of the use of antiepileptic drugs in high-grade central nervous system
      tumors.
AB  - BACKGROUND: Seizures are a common complication in patients with central nervous
      system (CNS) tumors. Optimal management is unclear with no defined guidelines and
      pharmacological management poses many controversies. Due to a hypothesized lack
      of consistency, we aimed to retrospectively review seizure management in patients
      with high-grade CNS tumors in our institution. METHODS: The medical records of
      patients with high-grade CNS tumors referred to the specialist palliative
      medicine service in our institution from January-June 2008 were retrospectively
      reviewed. Seizure incidence, antiepileptic drug (AED) choice, neurology input,
      medication interactions, and appropriate drug level monitoring were assessed.
      RESULTS: Twenty-seven patients were included for analysis. Fifteen (56%) were
      female. The mean age was 58.8 years (range 31-82 years). Three (11%) patients
      presented with seizures and 8 (30%) developed seizures subsequently. Eight (73%
      of those with seizures) were on monotherapy AED. Six different agents were used
      as first-line agents. Phenytoin was the most common AED used (n = 4). Three (27%)
      patients were on combination AEDs. Five (45.5%) patients had been seen by
      neurology and 6 (54.5%) had appropriate drug level monitoring performed. Six
      (55%) patients had potential AED-non-AED interactions. None of the patients had
      instructions documented in the clinical notes against driving. CONCLUSION:
      Seizure management in patients with CNS tumors is not consistent and remains very
      much a neglected area. Appropriate choice of AED is crucial. Physicians should be
      aware of potential drug interactions. Ownership and regular follow-up of this
      group is required to ensure optimum patient management.

PMID- 22363033
TI  - A pilot study of palliative medicine fellows' hospice home visits.
AB  - This was a prospective descriptive study of hospice physician home visits (HVs)
      conducted by Hospice and Palliative Medicine Fellows. Our objectives were 1) to
      improve our knowledge of hospice care at home by describing physician HVs 2) to
      identify the indications for physician HVs and the problems addressed during the
      HV. Data was collected on 58 consecutive patients using a standardized form
      completed before and after the home visit. More than half of the persons were
      women. Most were Caucasian. Median age was 75 years; 57% had cancer; 77% were do
      not-resuscitate. 76% HV occurred in the home. The median visit duration was 60
      minutes; median travel distance and time 25 miles and 42 minutes, respectively. A
      hospice nurse case manager was present in 95%. The most common issues addressed
      during HVs were: health education, symptom management, and psychosocial support.
      Medication review was prominent. Physicians identified previously unreported
      issues. Symptom control was usually pain, although 27 symptoms were identified.
      Medications were important; all home visits included drug review and two thirds
      drug change. Physicians had unique responsibilities and identified important
      issues in the HV. Physicians provided both education and symptom management.
      Physician HVs are an important intervention. HVs were important in continuity of
      care, however, time-consuming, and incurred considerable travel, and professional
      time and costs.

PMID- 22363034
TI  - Multisystem atrophy made worse by lithium treatment in a hospice patient: a case
      report.
AB  - Multisystem atrophy is a neurologic condition defined as an adult-onset,
      progressive, neurodegenerative disease of unknown etiology. It carries a
      multisystem clinical course, including autonomic, urogenital, cerebellar, and
      parkinsonian features. Lithium toxicity, classically manifesting as increased
      thirst, polyuria, gastric distress, weight gain, tremor, fatigue, and mild
      cognitive impairment, can present in a similar manner.(1) We would like to
      present a patient diagnosed with progressive neurologic features typical of
      multisystem atrophy that also had bipolar disorder and had been taking lithium
      for many years. Despite normal lithium levels, it appeared as though a
      subclinical lithium toxicity was manifesting in the patient, and once lithium was
      discontinued, the patient was discharged from hospice with significant
      improvement in his presenting symptoms.

PMID- 22363035
TI  - A protocol for the acute control of agitation in palliative care: a preliminary
      report.
AB  - Agitation is one of the most frequent causes for palliative sedation. It often
      requires urgent control to avoid negative consequences and even endangerment of
      all involved, including the patients themselves. A protocol for the control of
      episodes of agitation was developed, based on a previous experience. The protocol
      includes a combination of haloperidol and midazolam. The protocol was used 86
      times in 27 patients. Each patient was sedated from 1 to 12 times, median 2
      times. The median time from the beginning of sedation to the control of agitation
      was 15 minutes with a range from 1 minute (2 cases) to 3 hours and 5 minutes
      (only 1 case). In 71 cases (83%), only the first dose was needed. There were no
      significant complications.

PMID- 22363036
TI  - The 70th anniversary of the death of Lou Gehrig.
AB  - The year 2011 marked the 70th anniversary of the death of Lou Gehrig. This
      article reviews his history, illness, relationship with his physicians, and what
      the modern physician can learn from his story. Lou Gehrig's disease continues to
      be the popular eponym for amyotrophic lateral sclerosis.

PMID- 22363037
TI  - Palliative chemotherapy for malignant ascites secondary to ovarian cancer.
AB  - Although research has shown that palliative chemotherapy is beneficial compared
      to lack of treatment (Schorge JO, Schaffer JI, Halvorson LM, et al. ed. Williams
      Gynecology. New York, NY: McGraw Hill Medical; 2008.), other studies show
      aggressive end-of-life treatment adversely affects quality of life and shortens
      life span (Arriba L, Fader A, Frasure H, von Gruenigen V. A review of issues
      surrounding quality of life among women with ovarian cancer. Gynecol Oncol.
      2010;119(2):390-396.). Without a consensus on palliative chemotherapy,
      underutilization during end of life prevails, and likely will continue without
      additional research (Barbera L, Elit L, Krzyzanowska M, et al. End of life care
      for women with gynecologic cancers. Gynecol Oncol. 2010;118(2):196-201.). This
      article aims to evaluate and examine existing chemotherapy for palliation of
      malignant ascites secondary to ovarian cancer and compare commonly used regimens.
      Agents will be evaluated by their modes of administration. Oral agents include
      cyclophosphamide and thalidomide, and intraperitoneal vehicles include taxane
      based agents, platinum-based agents, antibiotics, and biologic agents. In
      addition, cost, ethics, and quality of life discussions factor into this review.
      Palliative care's goal is to find a balance between life expectancy and symptom
      relief with minimal adverse effects.

PMID- 22363038
TI  - Spiritual needs and spiritual care for veterans at end of life and their
      families.
AB  - Spiritual care is an important domain of palliative care programs across the
      country and in the Veterans Affairs (VA) Healthcare System specifically. This
      qualitative study assessed the spiritual needs, spiritual care received, and
      satisfaction with spiritual care of both Veterans at the end of life and their
      families. Seventeen Veterans and 9 family members participated. They expressed a
      wide range of spiritual needs, including a wish of Veterans to have a better
      understanding of traumatic events that occurred during their combat experience.
      Some Veterans reported military experience enhanced their spirituality.
      Generally, respondents reported satisfaction with VA spiritual care, but
      indicated that Veterans may benefit from greater access to VA chaplains and
      explicit discussion of the impact of their military experience on their
      spirituality.

PMID- 22363039
TI  - Concept analysis of good death in terminally ill patients.
AB  - The purpose of this concept analysis of good death was to examine the attributes
      of a good death and explore the changes of the concept over time and its impact
      on terminally ill patients. The method used for this analysis was the Rodgers'
      evolutionary method. A literature search was completed using Medline Ovid and
      Journal Storage (JSTOR).The findings describe the evolution of the good death
      concept over time from the prehistoric era followed by premodern, modern, and
      postmodern times. In addition, information is presented about surrogate terms,
      attributes, antecedents, and consequences associated with good death followed by
      analysis and discussion of the findings. General attributes of a good death
      include pain and symptom management, awareness of death, patient's dignity,
      family presence, family support, and communication among patient, family, and
      health care providers.

PMID- 22363040
TI  - Most advance directives written by patients with advanced cancer or their proxies
      request only minimally invasive treatments during end-of-life care.
AB  - Although it is assumed that most patients with terminal cancer are reluctant to
      receive life-sustaining treatment, there is a paucity of evidence supporting this
      assumption. We retrospectively analyzed the advance directives of terminal cancer
      patients to determine the preferences of patients. Patients with cancer who had
      life expectancy of less than 6 months were admitted to a palliative care unit in
      Seoul Medical Center from March 2008 to February 2010. Among a total of 247
      patients, advance directives were present in the medical records of 168 patients
      (68.0%). Most of the advance directives were written by the patients' families
      (95.2%) and they stated that they did not want most of the invasive procedures.
      Patients with advanced cancer mostly requested that only minimally invasive
      treatments that eased suffering be performed.

PMID- 22363041
TI  - Close relatives find meaning to cope with cancer diagnosis and treatment of
      family members.
AB  - Pediatric palliative care has recently become a priority in the health care field
      and is implemented at the time of diagnosis rather than days or weeks before the
      child's death. Social constructivism theory in which humans generate meaning from
      their experiences was utilized as a general framework to determine the impact of
      pediatric palliative care on close relatives. The purpose of this grounded theory
      study was to generate a substantive theory that explains how close relatives such
      as grandparents, aunts, and uncles of a child with cancer experience palliative
      care. The participants of the study included close relatives of children in
      palliative care. Semistructured interviews and journaling were used to collect
      data. Initial, focused, and axial coding procedures were used to manage the data
      and a content analysis of the textual data was performed. Findings from the data
      suggested a process of finding meaning which helps close relatives to let go of
      what they cannot control while holding on to what they can control. Social change
      implications of this study may include improving health care programming for
      close relatives utilizing supportive-expressive measures. This programming may
      promote mental health of the close relatives who will learn to deal with their
      adjustment difficulties and improve their coping skills.

PMID- 22363042
TI  - Outcomes of critically ill gynecological cancer patients admitted to intensive
      care unit.
AB  - PURPOSE: To assess the characteristics of critically ill patients with
      gynecological cancer, and to evaluate their prognosis. METHODS: Fifty-two
      critically ill patients with gynecological cancer admitted to intensive care unit
      (ICU) were included. Univariate and multivariate logistic regressions were used
      to identify factors associated with hospital mortality. RESULTS: Thirty-five
      patients (67.3%) had carcinoma of the cervix uteri and 11 (21.2%) had ovarian
      cancer. The mortality rate in the ICU was 17.3% (9 of 52) and hospital mortality
      rate were 23%(12 of 52). In the multivariate analysis, independent prognostic
      factors for hospital mortality were vasopressor use (odds ratio [OR] = 8.60, 95%
      confidence interval [CI] 2.05-36; P = .03) and the Acute Physiology and Chronic
      Health Evaluation (APACHE) II score (OR = 1.43, 95% CI 1.01-2.09; P = .048).
      CONCLUSIONS: The independent prognostic factors for hospital mortality were the
      need for vasopressors and the APACHE II score.

PMID- 22363043
TI  - Determinants of parental satisfaction with ultrasound hip screening in child
      health care.
AB  - Prior research has shown ultrasound (US) screening for developmental dysplasia of
      the hip (DDH) in preventive child health care to be more effective than the
      current screening method. In the present study, 3-month-old infants were screened
      for DDH with US. The objective of this study was to examine parental satisfaction
      with the screening and determinants that affect satisfaction. Parental
      satisfaction was measured using a questionnaire. Independent variables included
      socio-demographic determinants, structure, process and outcome-related
      determinants and the meeting of expectations. Satisfaction with the screening was
      high. Parents who perceived the screener as competent, had enough time to ask
      questions, perceived the proceeding as fluent, perceived a low burden on their
      infant and whose expectations were met, were more likely to be satisfied.
      Satisfaction was influenced by process-related factors and not by factors related
      to the structure and the outcome of the screening. Good information provision
      before the screening and communication during the screening are means by which
      parental satisfaction can be influenced positively.

PMID- 22363044
TI  - Patterns and correlates of multiple risk factors for adult-onset cancer among
      adolescents(1).
AB  - The authors investigated patterns and correlates of multiple cancer risk factors
      (MCRFs) among adolescents. Baseline data from an intervention efficacy trial were
      analyzed to examine patterns of co-occurring MCRFs and sociodemographic and
      theoretical (e.g. prevention self-efficacy) correlates of MCRFs among adolescents
      (N = 50) aged 13-21 years. The mean total MCRFs was 4.6 (SD = 1.6; range = 0-9).
      The most common risk factors were intentions to use alcohol (n = 40, 80%), <5
      daily servings of fruits/vegetables (n = 40, 80%), and lifetime alcohol use (n =
      38, 76%). MCRFs commonly co-occurred, suggesting a clustered risk profile. Higher
      age (B = 0.19, 95% confidence interval [CI]: 0.01, 0.38) and lower prevention
      self-efficacy (B = -0.16, 95% CI: -0.30, -0.02) were significantly (p < 0.05)
      associated with MCRFs. Multiple health behavior change interventions are needed
      to prevent accumulation of risk factors as youth mature. Self-efficacy may be an
      important target for prevention interventions.

PMID- 22363045
TI  - Using genograms to understand pediatric practices' readiness for change to
      prevent abuse and neglect.
AB  - A novel use of genograms in primary care practice is to identify processes and
      relationships among physicians and staff prior to implementing practice change.
      The authors hypothesized that the genogram would inform researchers and practice
      staff, participating in a child maltreatment prevention study, how practice
      members function in a practice. They describe the use of genograms and show how
      the genogram results are associated with intervention uptake. Researchers
      constructed genograms, collected baseline surveys, and conducted postintervention
      interviews with physicians. Data were analyzed to determine processes associated
      with intervention uptake. While survey results supported the relationships and
      conflicts observed in the genograms, the genogram provided more multilevel
      information that reflected practices' abilities to implement change. By providing
      a snapshot of the relationship and organizational dynamics within a practice,
      genograms can assess culture for practice change. Genograms describe
      organizational dynamics and are useful tools to use prior to initiating new
      programs.

PMID- 22363046
TI  - How children's rights are constructed in family-centred care: a review of the
      literature.
AB  - It appears that the acceptance of children's rights within the acute care setting
      is treated as a given but such a given requires a more systematic analysis. This
      has been undertaken here in the form of a review of the literature. The purpose
      of the review is to explore how children's rights, defined by the United Nations
      Convention on the Rights of the Child (UNCRC) are recognized in family-centred
      care in the acute care paediatric setting as reported in the literature. Reports
      that were available from 1989 to 2010 were reviewed. Children's rights are not
      mentioned frequently in the literature of interest to children's nurses. What is
      revealed are the ethical tensions in the challenge to act at all times in
      children's best interests (in the spirit of Article 3) while giving due weight to
      their views (in the spirit of Article 12) (OHCHR, 1989). The continuing failure
      to address these tensions undermines the spirit and practice of family-centred
      care.

PMID- 22363047
TI  - Cardiorespiratory fitness, weight status and objectively measured sedentary
      behaviour and physical activity in rural and urban Portuguese adolescents.
AB  - Relationships among weight status (body mass index [BMI]), cardiorespiratory
      fitness (CRF) and objective measures of sedentary behaviour and physical activity
      (PA) were considered in a cross-sectional sample of Portuguese adolescents. The
      sample included 362 youth aged 13-16 years (165 males, 197 females) from urban
      and rural regions of the Portuguese midlands. CRF was assessed with the 20-m
      shuttle-run test. An uniaxial accelerometer was used to obtain five consecutive
      days of activity behaviours including time being sedentary. Pearson correlations
      and logistic regression analysis were used to examine relationships among
      variables. Rural adolescents were less active than their urban peers over the
      weekend. Both rural and urban youth with higher levels of CRF had a lower
      relative risk of being overweight/obese. The observations indicate important
      associations between weight status and CRF in both rural and urban Portuguese
      adolescents. In addition, place of residence has an important impact on weight
      status of this sample of adolescents.

PMID- 22363048
TI  - Disordered eating behavior and body weight and shape relatives' criticism in
      overweight and obese 15- to 19-year-old females.
AB  - This study evaluated the link between relatives' criticism of overweight or obese
      teenage girls' figure and body weight and their relationship with their mothers,
      fathers and siblings, affection, self-esteem, the internalization of the
      aesthetic body thin ideal, depressive symptoms and disordered eating behaviors
      (DEB). The sample comprised 2174 senior high school students aged 15 to 19.
      Teenagers criticized by their relatives showed higher DEB, without interaction
      between Body Mass Index (BMI) and DEB. The structural equations model showed DEB
      was primarily explained by the internalization of the body aesthetic thin ideal,
      family's criticism, BMI and depressive symptoms.

PMID- 22363049
TI  - Social support and invalidation by others contribute uniquely to the
      understanding of physical and mental health of patients with rheumatic diseases.
AB  - This study examined whether social support and invalidation (lack of
      understanding and discounting by others) are differently associated with physical
      and mental health. Participants were 1455 patients with fibromyalgia, rheumatoid
      arthritis, ankylosing spondylitis, osteorarthritis, or another rheumatic disease.
      Participants completed online questionnaires. Social support correlated
      negatively with discounting responses of others (moderately) and lack of
      understanding (strongly). Both invalidation and social support were additively
      associated with patients' mental health, but only discounting was significantly
      associated with patients' physical health. This suggests that improving health of
      patients with rheumatic diseases requires the consideration of both social
      support and invalidation.

PMID- 22363050
TI  - From lymph to fat: liposuction as a treatment for complete reduction of
      lymphedema.
AB  - There is some controversy regarding liposuction for late-stage lymphedemas.
      Although it is clear that conservative therapies such as complex decongestive
      therapy and controlled compression therapy should be tried in the first instance,
      options for the treatment of late-stage lymphedema that is not responding to
      treatment is not so clear. Liposuction has been used for many years to treat
      lipodystrophy. Some results have been far from optimal; however, improvements in
      technique, patient preparation, and patient follow-up have led to a greater and a
      wider acceptance of liposuction as a treatment for lymphedema. This article
      outlines the benefits of using liposuction and presents the evidence to support
      its use.

PMID- 22363051
TI  - An admission bioclinical score to predict 1-year outcomes in patients undergoing
      aneurysm coiling.
AB  - BACKGROUND AND PURPOSE: A number of scores were developed to predict outcomes
      after clipping for subarachnoid hemorrhages, yet there is no score for patients
      undergoing endovascular treatment. Our goal was to develop, compare, and validate
      a predictive score for 1-year outcomes in patients with coiled subarachnoid
      hemorrhage. METHODS: We studied 526 patients for 1 year after intensive care unit
      discharge. We developed an admission bioclinical score (ABC score), which
      integrated biomarkers such as troponin I and S100beta, with the Glasgow Coma
      Scale. Using the receiver operating characteristic curve (95% CI), the ABC score
      was compared with the Glasgow Coma Scale, World Federation of Neurosurgical
      Societies score, and Fisher score in the derivation cohort and further validated
      in an independent cohort. RESULTS: In the derivation cohort (from 2003-2007,
      n=368), multivariate logistic regression analysis showed that only Glasgow Coma
      Scale (P<0.001), high S100beta (P<0.001), and high troponin (P<0.02) were
      independently associated with 1-year mortality. Troponin, S100beta, and Glasgow
      Coma Scale were thus integrated to derive the ABC score. In the derivation
      cohort, the ABC score reached an receiver operating characteristic curve of 0.82
      (0.77-0.88, P<0.001) and was significantly greater than the receiver operating
      characteristic curves of the Glasgow Coma Scale, World Federation of
      Neurosurgical Societies, and Fisher scores for predicting 1-year mortality. In
      the validation cohort (from 2008-2009, n=158), the ABC score's receiver operating
      characteristic curve of 0.76 (0.67-0.86, P<0.001) remained superior to the 3
      other scores for predicting 1-year mortality. CONCLUSIONS: The ABC score improves
      1-year outcome prediction at admission for patients with coiled subarachnoid
      hemorrhage. Our study provides large cohort-based evidence supporting integration
      of individual biomarkers and clinical characteristics to predict outcomes.
      Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier:
      NCT01357057.

PMID- 22363052
TI  - Socioeconomic status and stroke: an updated review.
AB  - BACKGROUND AND PURPOSE: Rates of stroke incidence and mortality vary across
      populations with important differences between socioeconomic groups worldwide.
      Knowledge of existing disparities in stroke risk is important for effective
      stroke prevention and management strategies. This review updates the evidence for
      associations between socioeconomic status and stroke.  Summary of Review- Studies
      were identified with electronic searches of MEDLINE and EMBASE databases (January
      2006 to July 2011) and reference lists from identified studies were searched
      manually. Articles reporting the association between any measure of socioeconomic
      status and stroke were included. CONCLUSIONS: The impact of stroke as measured by
      disability-adjusted life-years lost and mortality rates is >3-fold higher in low
      income compared with high- and middle-income countries. The number of stroke
      deaths is projected to increase by >30% in the next 20 years with the majority
      occurring in low-income countries. Higher incidence of stroke, stroke risk
      factors, and rates of stroke mortality are generally observed in low compared
      with high socioeconomic groups within and between populations worldwide. There is
      less available evidence of an association between socioeconomic status and stroke
      recurrence or temporal trends in inequalities. Those with a lower socioeconomic
      status have more severe deficits and are less likely to receive evidence-based
      stroke services, although the results are inconsistent. Poorer people within a
      population and poorer countries globally are most affected in terms of incidence
      and poor outcomes of stroke. Innovative prevention strategies targeting people in
      low socioeconomic groups are required along with effective measures to promote
      access to effective stroke interventions worldwide.

PMID- 22363053
TI  - Hemodynamic differences between unruptured and ruptured intracranial aneurysms
      during observation.
AB  - BACKGROUND AND PURPOSE: We evaluated several hemodynamic parameters for the
      prediction of rupture in a data set of initially unruptured aneurysms, including
      aneurysms that ruptured during follow-up observation. METHODS: Aneurysm geometry
      was extracted from CT angiographic images and analyzed using a mathematical
      formula for fluid flow under pulsatile blood flow conditions. Fifty side-wall
      internal carotid posterior communicating artery aneurysms and 50 middle cerebral
      artery bifurcation aneurysms of medium size were investigated for energy loss,
      pressure loss coefficient, wall shear stress, and oscillatory shear index. During
      follow-up observation, 6 internal carotid posterior communicating artery and 7
      middle cerebral artery aneurysms ruptured (44 and 43 remained unruptured,
      respectively, with the same location and a similar size as the ruptured cases).
      RESULTS: A significant difference in the minimum wall shear stress between
      aneurysms that ruptured and those that remained unruptured was noted only in
      internal carotid artery aneurysms (P<0.001). Energy loss showed a higher tendency
      in ruptured aneurysms but statistically not significant. For pressure loss
      coefficient, a significant difference was noted in both internal carotid artery
      (P=0.0046) and middle cerebral artery (P<0.001) aneurysms. CONCLUSIONS: Pressure
      loss coefficient may be a potential parameter to predict future rupture of
      unruptured aneurysms.

PMID- 22363054
TI  - Risk factors and outcome of patients with symptomatic intracranial stenosis
      presenting with lacunar stroke.
AB  - BACKGROUND AND PURPOSE: We hypothesized that patients with intracranial stenosis
      with lacunar stroke presentations would face lower risks of recurrent stroke than
      those with index nonlacunar strokes, and that their recurrent strokes would
      predominantly be lacunar. METHODS: We analyzed subjects enrolled with an index
      stroke into the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial.
      The index stroke was classified as lacunar or nonlacunar. The primary end point
      was recurrent ischemic stroke. Cox proportional hazard models were generated with
      stratification for severity of stenosis. RESULTS: Three hundred forty-seven
      subjects were enrolled after an index stroke; 38 were lacunar and 309 were
      nonlacunar. Over a mean follow-up of 1.8 years, there was no significant
      difference in stroke recurrence between patients whose index stroke was lacunar
      (7 of 38 [18%]) versus nonlacunar (69 of 309 [22%]; hazard ratio, 0.79; 95% CI,
      0.36-1.71). Furthermore, no significant differences were found when groups were
      stratified by 50% to 69% stenosis (hazard ratio, 0.50; 95% CI, 0.12-2.1) and >=
      70% stenosis (hazard ratio, 0.87; 95% CI, 0.34-2.2). Of the 7 recurrent strokes
      in patients whose index stroke was lacunar, all 7 were nonlacunar and 3 were in
      the territory of the stenotic artery. CONCLUSIONS: In patients with symptomatic
      intracranial stenosis, the risk of recurrent stroke was similar in patients who
      presented with lacunar and nonlacunar strokes, and recurrent strokes in patients
      presenting with lacunar stroke were typically nonlacunar. These findings suggest
      that the pathophysiology of these strokes is related to the stenosis rather than
      small vessel disease. Patients presenting with lacunar strokes should be included
      in trials investigating secondary prevention for symptomatic intracranial
      stenosis.

PMID- 22363055
TI  - Alternatively-spliced extra domain A of fibronectin promotes acute inflammation
      and brain injury after cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: The fibronectin isoform containing the alternatively
      spliced extra domain A (EDA(+)-FN) is normally absent from the circulation, but
      plasma levels of EDA(+)-FN can become markedly elevated in several human
      pathological conditions associated with inflammation including ischemic stroke.
      It remains unknown whether EDA(+)-FN contributes to stroke pathogenesis or is
      simply an associative marker. Several in vitro studies suggest that EDA(+)-FN can
      activate Toll-like receptor 4, an innate immune receptor that triggers
      proinflammatory responses. We undertook a genetic approach in mice to investigate
      the ability of EDA(+)-FN to mediate inflammatory brain damage in a focal cerebral
      ischemia/reperfusion injury model. METHODS: We used genetically modified EDA(+/+)
      mice, which constitutively express EDA(+)-FN. Extent of injury, neurological
      outcome, and inflammatory mechanisms were assessed after 1-hour cerebral
      ischemia/23-hour reperfusion injury and compared with wild-type mice. RESULTS: We
      found that EDA(+/+) mice developed significantly larger infarcts and severe
      neurological deficits that were associated with significant increased neutrophil
      and macrophage infiltration as quantitated by immunohistochemistry. Additionally,
      we found upregulation of nuclear factor-kappaB, cyclo-oxygenase-2, and
      inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 in the EDA(+/+) mice compared with wild-type mice. Interestingly,
      increased brain injury and neurological deficits were largely abrogated in
      EDA(+/+) mice by treatment with a specific Toll-like receptor 4 inhibitor.
      CONCLUSIONS: These findings provide the first evidence that EDA(+)-FN promotes
      inflammatory brain injury after ischemic stroke and suggest that the elevated
      levels of plasma EDA(+)-FN observed in chronic inflammatory conditions could
      worsen injury and outcome in patients after acute stroke.

PMID- 22363056
TI  - Tissue factor pathway inhibitor, activated protein C resistance, and risk of
      ischemic stroke due to postmenopausal hormone therapy.
AB  - BACKGROUND AND PURPOSE: To test whether changes in plasma tissue factor pathway
      inhibitor (TFPI) levels or activated protein C resistance (normalized activated
      protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke
      due to postmenopausal hormone therapy. METHODS: Nested case-control study of 455
      cases of ischemic stroke and 565 matched control subjects in the Women's Health
      Initiative trials of postmenopausal hormone therapy. RESULTS: Baseline free TFPI
      was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01
      1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI,
      0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of
      postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes
      of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic
      stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses,
      baseline nAPCsr was inversely associated with lacunar strokes (OR per SD
      increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted
      with treatment to increase large vessel atherosclerotic strokes (P=0.008).
      CONCLUSIONS: Procoagulant changes in TFPI or nAPCsr do not modify the increased
      ischemic stroke risk due to postmenopausal hormone therapy.  Clinical Trial
      Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT 00000611.

PMID- 22363057
TI  - Endovascular therapy of 623 patients with anterior circulation stroke.
AB  - BACKGROUND AND PURPOSE: Endovascular therapy of acute ischemic stroke has been
      shown to be beneficial for selected patients. The purpose of this study is to
      determine predictors of outcome in a large cohort of patients treated with intra
      arterial thrombolysis, mechanical revascularization techniques, or both. METHODS:
      We prospectively acquired data for 623 patients with acute cerebral infarcts in
      the carotid artery territory who received endovascular treatment at a single
      center. Logistic regression analysis was performed to determine predictors of
      outcome. RESULTS: Median National Institutes of Health Stroke Scale (NIHSS) at
      admission was 15. Partial or complete recanalization was achieved in 70.3% of
      patients; it was independently associated with hypercholesterolemia (P=0.02),
      absence of coronary artery disease (P=0.023), and more proximal occlusion site
      (P<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients
      reached favorable outcome (modified Rankin scale score 0-2). Good collaterals
      (P<0.0001), recanalization (P=0.023), hypercholesterolemia (P=0.03), lower NIHSS
      at admission (P=0.001), and younger age (P<0.0001) were independent predictors
      for survival. More peripheral occlusion site (P<0.0001), recanalization
      (P<0.0001), hypercholesterolemia (P=0.002), good collaterals (P=0.002), lower
      NIHSS (P<0.0001), younger age (P<0.0001), absence of diabetes (P=0.002), and no
      previous antithrombotic therapy (P=0.036) predicted favorable outcome. Time to
      treatment was only a predictor of outcome, when collaterals were excluded from
      the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was
      independently predicted by poor collaterals (P=0.004). CONCLUSIONS: Several
      independent predictors for outcome and complications were identified. Unlike in
      intravenous thrombolysis trials, time to treatment was a predictor of outcome
      only when collaterals were excluded from the model, indicating the important role
      of collaterals for the time window.

PMID- 22363058
TI  - Organized blood pressure control programs to prevent stroke in Australia: would
      they be cost-effective?
AB  - BACKGROUND AND PURPOSE: High blood pressure (BP) is the most important modifiable
      stroke risk factor. Worldwide high BP in many people is uncontrolled or people
      are unaware of their BP status. We aimed to assess whether a program of organized
      multidisciplinary care and medication would be cost-effective for improving BP
      control for the prevention of stroke. METHODS: A novel aspect was to simulate the
      intervention to match recent primary care initiatives (eg, new Medicare
      reimbursement items) to ensure policy relevance. Current practice and additional
      costs of each intervention were included using the best available evidence. The
      differences in the cost per quality-adjusted life year (QALY) gained for the
      interventions were compared against current practice. Cost-effectiveness was
      defined as cost per QALY gained was less than Australian dollars (AUD) 50 000
      (societal perspective; reference year 2004). The robustness of estimates was
      assessed with probabilistic multivariable uncertainty analysis. RESULTS: For
      primary prevention, the median cost per QALY gained was AUD11 068 (95%
      uncertainty interval AUD5201 to AUD18 696) in those aged 75 years or older and
      was AUD17 359 (95% uncertainty interval AUD10 516 to AUD26 036) in those aged 55
      to 84 years with >=15% absolute risk of stroke. Primary prevention interventions
      were not cost-effective if aged younger than 50 years. The median cost per QALY
      gained for secondary prevention was AUD1811 and AUD4704, depending on which
      medications were modeled. CONCLUSIONS: Organized care for BP control targeted at
      specific populations offers excellent value over current practice. Organized care
      for secondary prevention provided the greatest benefits and strongest cost
      effectiveness. Translation into clinical practice requires improved use of
      relevant Medicare policy in Australia.

PMID- 22363059
TI  - Postradiosurgery hemorrhage rates of arteriovenous malformations of the brain:
      influencing factors and evolution with time.
AB  - BACKGROUND AND PURPOSE: The long-term benefit of radiosurgery of brain
      arteriovenous malformations (AVM), especially nonhemorrhagic cases, is
      controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed
      the risk factors for bleeding based on cases followed at our site. METHODS: One
      hundred eight patients, age 36 +/- 17 years, 56 men. The mean follow-up was 65 +/
      44 months (median, 54; interquartile range, 33-94). Most AVMs were small (74.1%
      <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep
      drainage, and 39.8% presented with hemorrhage. RESULTS: The annual hemorrhage
      rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic
      presentation. Older patients, cortical or subcortical AVMs, and cases with
      multiple draining veins were less likely to present with bleeding. During the
      first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%,
      and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage
      rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension
      and nidus volume were independent predictors of bleeding after treatment. Mean
      nidus obliteration time was 37 +/- 18 months (median, 32; interquartile range, 25
      40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9%
      for AVMs that were not closed at the end of follow-up. CONCLUSIONS: Both
      hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with
      gradual decrease in their bleeding rates over the years. Albeit small, the risk
      of hemorrhage persists during the entirety of follow-up, being higher for cases
      with hemorrhagic presentation and nonobliterated AVM.

PMID- 22363060
TI  - Dietary flavonoids and risk of stroke in women.
AB  - BACKGROUND AND PURPOSE: To date, few studies have examined associations between
      the wide range of flavonoid subclasses and risk of ischemic, hemorrhagic, and
      total stroke. METHODS: We conducted a prospective study among 69 622 women from
      the Nurses' Health Study. Total flavonoid and subclass intakes were calculated
      from semiquantitative food frequency questionnaires collected every 4 years using
      an updated and extended US Department of Agriculture flavonoid database. RESULTS:
      During 14 years of follow-up, 1803 incident strokes were confirmed. After
      adjusting for potential confounders, women in the highest compared with the
      lowest quintile of flavanone intake had a relative risk of ischemic stroke of
      0.81 (95% CI, 0.66-0.99; P=0.04). Citrus fruits/juices, the main dietary source
      of flavanones, tended to be associated with a reduced risk for ischemic stroke
      (relative risk, 0.90; 95% CI, 0.77-1.05) comparing extreme quintiles.
      CONCLUSIONS: Total flavonoid intake was not inversely associated with risk of
      stroke; however, increased intake of the flavanone subclass was associated with a
      reduction in the risk of ischemic stroke. Citrus fruit consumption may be
      associated with a reduction in stroke risk, and experimental data support these
      epidemiological associations that the flavanone content of citrus fruits may
      potentially be cardioprotective. Further prospective studies are needed to
      confirm these associations.

PMID- 22363061
TI  - Myelin loss associated with neuroinflammation in hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Small vessel disease is the major cause of white matter
      injury in patients with vascular cognitive impairment. Matrix metalloproteinase
      (MMP)-mediated inflammation may be involved in the white matter damage with
      oligodendrocyte (Ol) death. Therefore, we used spontaneously hypertensive stroke
      prone rats to study the role of neuroinflammation in white matter damage.
      METHODS: Permanent unilateral carotid artery occlusion was performed at 12 weeks
      of age in spontaneously hypertensive stroke-prone rats. Following surgery, rats
      were placed on a Japanese permissive diet and received 1% NaCl in drinking water.
      MRI, histology, biochemistry, and ELISA characterized white matter lesions, and
      cognitive impairment was tested by Morris water maze. RESULTS: White matter
      damage was observed 4 to 5 weeks following permanent unilateral carotid artery
      occlusion/Japanese permissive diet. Immunoblotting showed marked reduction in
      myelin basic protein and upregulation of immature Ols. Mature Ols underwent
      caspase-3-mediated apoptosis. Morris water maze showed cognitive impairment.
      Abnormally appearing vessels were observed and surrounded by inflammatory-like
      cells. IgG extravasation and hemorrhage, indicating blood-brain barrier (BBB)
      disruption, was closely associated with MMP-9 expression. Lesions in white matter
      showed reactive astrocytosis and activated microglia that expressed tumor
      necrosis factor-alpha. MMP-3 and MMP-9 were significantly increased, and MMP-2
      was reduced in both astrocytes and Ol. CONCLUSIONS: We found apoptosis of mature
      Ols with an increase in immature Ols. Increased MMP-3, MMP-9, and tumor necrosis
      factor-alpha were associated with myelin breakdown and BBB disruption.
      Neuroinflammation is an important factor in white matter damage and Ol death, and
      studies using this new model can be performed to assess agents to block
      inflammation.

PMID- 22363062
TI  - Contrast delay on perfusion CT as a predictor of new, incident infarct: a
      retrospective cohort study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine if the
      assessment of intracranial collateral circulation by CT angiography and/or
      perfusion CT (PCT) can predict the risk of future ischemic stroke in a large,
      retrospective cohort study. METHODS: We identified 135 consecutive patients who
      underwent CT angiography of the head and neck and PCT of the brain at baseline
      and with subsequent follow-up brain imaging. Clinical and demographic information
      and carotid wall features were collected. Collateral circulation was assessed
      anatomically at CT angiography and functionally by measuring the mean transit
      time delay at PCT. The clinical, carotid, CT angiography, and PCT variables were
      compared between those with and without new incident infarct at follow-up imaging
      using mixed effect logistic statistical models. RESULTS: During the follow-up
      period, 15 patients developed a new infarct and 120 patients did not. Clinical
      features associated with the stroke risk were age, hypertension, hyperlipidemia,
      and atrial fibrillation. The carotid features associated with stroke risk were
      wall thickness. Anatomic assessment of collaterals on CT angiography was not
      associated with stroke risk, whereas the functional assessment of collaterals
      (mean transit time delay on PCT) was associated with stroke risk. In a
      multivariate model, age, atrial fibrillation, and mean transit time delay (OR,
      22.8; P<0.001) were the only covariates that were independent predictors of
      future ischemic stroke. CONCLUSIONS: The mean transit time delay on PCT contains
      important physiological information and should not be discarded. Along with age
      and atrial fibrillation, this functional assessment of intracranial collateral
      circulation predicts the risk of future hemispheric infarct.

PMID- 22363063
TI  - Impact of primary stroke center certification on location of acute ischemic
      stroke care in Georgia.
AB  - BACKGROUND AND PURPOSE: Primary stroke centers (PSCs) are associated with greater
      rates of tissue plasminogen activator use and improved outcomes. The American
      Stroke Association has advocated for the preferential transport of stroke
      patients to PSCs. We investigated the impact of PSC certification on hospital
      stroke discharge patterns in Georgia communities with a choice between PSC and
      non-PSC. METHODS: We analyzed data from the Georgia Discharge Data System before
      (2004) and after stroke certification (2009). Only Metropolitan Statistical Areas
      containing >=1 PSC and >=1 non-PSC were included in the analysis. We calculated
      the odds of acute stroke discharge from a PSC in 2009 compared with 2004.
      RESULTS: In Georgia Metropolitan Statistical Areas with at least 1 PSC and 1 non
      PSC hospital, the percent of patients discharged from a subsequently designated
      PSC increased from 50.2% to 56.6% between 2004 and 2009 (OR, 1.29; P<0.0001). In
      4 Metropolitan Statistical Areas, the proportion of stroke discharges from PSCs
      increased, whereas in 2 Metropolitan Statistical Areas, there was no significant
      increase, and in 1, there was a trend toward less stroke discharges from PSCs.
      CONCLUSIONS: Although there has been an overall increase in stroke discharges
      from PSCs, the impact of stroke certification on patient destination was small
      and inconsistent across the state suggesting that local factors influence the
      location of hospitalization.

PMID- 22363064
TI  - Depression screening in stroke: a comparison of alternative measures with the
      structured diagnostic interview for the diagnostic and statistical manual of
      mental disorders, fourth edition (major depressive episode) as criterion
      standard.
AB  - BACKGROUND AND PURPOSE: Screening tools for depression and psychological distress
      commonly used in medical settings have not been well validated in stroke
      populations. We aimed to determine the accuracy of common screening tools for
      depression or distress in detecting caseness for a major depressive episode
      compared with a clinician-administered structured clinical interview for
      Diagnostic and Statistical Manual of Mental Disorders Fourth Edition as the gold
      standard. METHODS: Seventy-two participants >=3 weeks poststroke underwent a
      diagnostic interview for major depressive episode and completed the Patient
      Health Questionnaire-2 and -9, Hospital Anxiety and Depression Scale, Beck
      Depression Inventory-II, Distress Thermometer, and Kessler-10. Internal
      consistency, sensitivity, specificity, likelihood ratios, and posttest
      probabilities were calculated. Each measure was validated against the gold
      standard using receiver operating characteristic curves with comparison of the
      area under the curve for all measures. RESULTS: Internal consistency ranged from
      acceptable to excellent for all measures (Cronbach alpha=0.78-0.94). Areas under
      the curve (95% CI) for the Patient Health Questionnaire-2, Patient Health
      Questionnaire-9, Hospital Anxiety and Depression Scale depression and total
      score, Beck Depression Inventory-II, and Kessler-10 ranged from 0.80 (0.69-0.89)
      for the Kessler-10 to 0.89 (0.79-0.95) for the Beck Depression Inventory-II with
      no significant differences between measures. The Distress Thermometer had an area
      under the curve (95% CI) of 0.73 (0.61-0.83), significantly smaller than the Beck
      Depression Inventory-II (P<0.05). CONCLUSIONS: Apart from the Distress
      Thermometer, selected scales performed adequately in a stroke population with no
      significant difference between measures. The Patient Health Questionnaire-2 would
      be the most useful single screen given free availability and the shortest number
      of items.

PMID- 22363066
TI  - Discrepancy between cardiac and physical functional reserves in stroke.
AB  - BACKGROUND AND PURPOSE: Understanding the physiological limitations to exercise
      after stroke will assist the development of targeted therapies to improve
      everyday function. This study defines (1) whether exercise capacity is limited by
      the cardiovascular system (oxygen supply) or skeletal muscles (oxygen
      utilization); and (2) cardiac function and pumping capability in people with
      stroke. METHODS: Twenty-eight male participants with mild ischemic stroke (70 +/-
      6 years of age, 18 +/- 20 months poststroke) and 25 male, age-matched healthy
      control subjects performed a graded cardiopulmonary exercise test with gas
      exchange and noninvasive hemodynamic measurements. Maximal oxygen extraction was
      calculated as the ratio between peak oxygen consumption and peak cardiac output.
      Cardiac function and pumping capability were assessed by peak exercise cardiac
      power output (expressed in watts) and cardiac output. RESULTS: Peak oxygen
      consumption (18.4 +/- 4.6 versus 26.8 +/- 5.5 mL/kg/min, P<0.01) and arterial
      venous O(2) difference (9.3 +/- 2.5 versus 12.6 +/- 1.9 mlO(2)/100 mL of blood,
      P<0.01) were both reduced in stroke participants compared with healthy control
      subjects. In contrast, peak exercise cardiac power output (4.79 +/- 0.79 versus
      4.51 +/- 0.96 W, P=0.49), cardiac output (16.4 +/- 3.1 versus 17.1+/-2.5 L/min,
      P=0.41), and the pressure-generating capacity of the heart (127+/-11 versus 125
      +/- 14 mm Hg, P=0.97) were similar between stroke participants and healthy
      control subjects. CONCLUSIONS: The ability of skeletal muscles to extract oxygen
      is diminished after stroke. However, cardiac function and pumping capability are
      maintained. Appropriate therapies targeting muscle oxygen uptake such as exercise
      rehabilitation may improve exercise capacity after stroke.

PMID- 22363065
TI  - Are myocardial infarction--associated single-nucleotide polymorphisms associated
      with ischemic stroke?
AB  - BACKGROUND AND PURPOSE: Ischemic stroke (IS) shares many common risk factors with
      coronary artery disease (CAD). We hypothesized that genetic variants associated
      with myocardial infarction (MI) or CAD may be similarly involved in the etiology
      of IS. To test this hypothesis, we evaluated whether single-nucleotide
      polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD
      through genome-wide association studies were associated with IS. METHODS: Meta
      analyses of the associations between the 11 MI-associated SNPs and IS were
      performed using 6865 cases and 11 395 control subjects recruited from 9 studies.
      SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in
      high linkage disequilibrium was chosen. Logistic regression was performed within
      each study to obtain study-specific betas and standard errors. Meta-analysis was
      conducted using an inverse variance weighted approach assuming a random effect
      model. RESULTS: Despite having power to detect odds ratio of 1.09-1.14 for
      overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were
      significantly associated with overall IS and/or stroke subtypes after adjusting
      for multiple comparisons. CONCLUSIONS: Our results suggest that the major common
      loci associated with MI risk do not have effects of similar magnitude on overall
      IS but do not preclude moderate associations restricted to specific IS subtypes.
      Disparate mechanisms may be critical in the development of acute ischemic
      coronary and cerebrovascular events.

PMID- 22363068
TI  - Phase II study of sequential gemcitabine followed by docetaxel for recurrent
      Ewing sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma:
      results of Sarcoma Alliance for Research Through Collaboration Study 003.
AB  - BACKGROUND: Gemcitabine and docetaxel have a broad spectrum of clinical activity
      in patients with carcinoma. The Sarcoma Alliance for Research Through
      Collaboration conducted a phase II trial of gemcitabine in combination with
      docetaxel in children and adults with recurrent Ewing sarcoma (EWS), osteosarcoma
      (OS), or unresectable or recurrent chondrosarcoma. The primary objective was to
      determine the objective response rate using response evaluation criteria in solid
      tumors (RECIST). METHODS: Gemcitabine (675 mg/m2 i.v. over 90 minutes on days 1
      and 8) was administered in combination with docetaxel (75 mg/m2 i.v. over 1 hour
      on day 8) every 21 days. All patients received filgrastim or pegfilgrastim. A
      Bayesian formulation was used to determine the probability of achieving the
      target response rate for each subtype-0.35 for EWS and OS or 0.20 for
      chondrosarcoma. If the probability of achieving the target response rate was
      <0.05, the combination was considered inactive. Toxicity was graded according to
      common terminology criteria for adverse events (CTCAE), version 3.0. RESULTS:
      Fifty-three eligible patients were enrolled in the three subtype groups-OS (n =
      14), EWS (n = 14), and chondrosarcoma (n = 25). Toxicities included neutropenia,
      thrombocytopenia, fatigue, dyspnea, bronchospasm, edema, neuropathy, and liver
      function abnormalities. Dose modification for toxicity was required for eight
      patients during cycle 1 and 16 patients in subsequent cycles. Seven patients
      withdrew from therapy as a result of toxicity. No complete responses were
      observed. Partial responses were observed in OS (n = 1), EWS (n = 2), and
      chondrosarcoma (n = 2) patients. CONCLUSION: Gemcitabine in combination with
      docetaxel was associated with a probability of reaching the target 35% response
      rate of <5% in OS patients and 5.6% in EWS patients; the probability of reaching
      a 20% response rate in chondrosarcoma patients was 14%. DISCUSSION: The Bayesian
      formulation permitted estimation of the probability of achieving the target
      response rate for each subtype after each response evaluation. By allowing
      multiple looks at the data, this design stopped the trial after considering the
      probability of achieving the target response rate and accrual rate. Because this
      design did not specify a rule for declaring the treatment as "active", a direct
      comparison with a standard two-stage phase II design is not appropriate. The
      decision to close the EWS and chondrosarcoma subtype arms was based, in part, on
      slow accrual and was supported by the low probability of achieving the target
      response rate. The rate of enrollment, rather than the statistical design, had a
      significant effect on the trial duration.

PMID- 22363067
TI  - First-line cetuximab plus capecitabine in elderly patients with advanced
      colorectal cancer: clinical outcome and subgroup analysis according to KRAS
      status from a Spanish TTD Group Study.
AB  - Single-agent cetuximab is safe and active in elderly patients with advanced
      colorectal cancer (CRC). A cetuximab-capecitabine combination has not previously
      been tested in elderly patients with advanced CRC. MATERIAL AND METHODS: Sixty
      six patients with advanced CRC were treated with cetuximab as a 400 mg/m2 i.v.
      infusion followed by 250 mg/m2 i.v. weekly plus capecitabine at a dose of 1,250
      mg/m2 every 12 hours. After the inclusion of 27 patients, the protocol was
      amended for safety reasons, reducing the dose of capecitabine to 1,000 mg/m2
      every 12 hours. Thirty-nine additional patients were treated with the reduced
      dose of capecitabine. RESULTS: The overall response rate was 31.8%. KRAS status
      was determined in 58 patients (88%). Fourteen of 29 patients with wild-type KRAS
      tumors responded (48.3%; 95% confidence interval [CI], 29.4%-67.5%), compared
      with six of 29 patients with mutant KRAS tumors (20.7%; 95% CI, 8.0%-39.7%). The
      median progression-free survival (PFS) interval was 7.1 months. The median PFS
      interval for patients whose tumors were wild-type KRAS was significantly longer
      than for those with mutant KRAS tumors (8.4 months versus 6.0 months; p = .024).
      The high incidence of severe paronychia (29.6%) declined (7.7%) after
      capecitabine dose adjustment. CONCLUSIONS: Cetuximab plus capecitabine at a dose
      of 1,000 mg/m2 every 12 hours may be an alternative to more aggressive regimens
      in elderly patients with advanced wild-type KRAS CRC.

PMID- 22363069
TI  - A comparison of cigarette- and hookah-related videos on YouTube.
AB  - OBJECTIVE: YouTube is now the second most visited site on the internet. The
      authors aimed to compare characteristics of and messages conveyed by cigarette-
      and hookah-related videos on YouTube. METHODS: Systematic search procedures
      yielded 66 cigarette-related and 61 hookah-related videos. After three trained
      qualitative researchers used an iterative approach to develop and refine
      definitions for the coding of variables, two of them independently coded each
      video for content including positive and negative associations with smoking and
      major content type. RESULTS: Median view counts were 606,884 for cigarettes
      related videos and 102,307 for hookah-related videos (p<0.001). However, the
      number of comments per 1000 views was significantly lower for cigarette-related
      videos than for hookah-related videos (1.6 vs 2.5, p=0.003). There was no
      significant difference in the number of 'like' designations per 100 reactions (91
      vs 87, p=0.39). Cigarette-related videos were less likely than hookah-related
      videos to portray tobacco use in a positive light (24% vs 92%, p<0.001). In
      addition, cigarette-related videos were more likely to be of high production
      quality (42% vs 5%, p<0.001), to mention short-term consequences (50% vs 18%,
      p<0.001) and long-term consequences (44% vs 2%, p<0.001) of tobacco use, to
      contain explicit antismoking messages (39% vs 0%, p<0.001) and to provide
      specific information on how to quit tobacco use (21% vs 0%, p<0.001).
      CONCLUSIONS: Although internet user-generated videos related to cigarette smoking
      often acknowledge harmful consequences and provide explicit antismoking messages,
      hookah-related videos do not. It may be valuable for public health programmes to
      correct common misconceptions regarding hookah use.

PMID- 22363071
TI  - Tree-growth analyses to estimate tree species' drought tolerance.
AB  - Climate change is challenging forestry management and practices. Among other
      things, tree species with the ability to cope with more extreme climate
      conditions have to be identified. However, while environmental factors may
      severely limit tree growth or even cause tree death, assessing a tree species'
      potential for surviving future aggravated environmental conditions is rather
      demanding. The aim of this study was to find a tree-ring-based method suitable
      for identifying very drought-tolerant species, particularly potential substitute
      species for Scots pine (Pinus sylvestris L.) in Valais. In this inner-Alpine
      valley, Scots pine used to be the dominating species for dry forests, but today
      it suffers from high drought-induced mortality. We investigate the growth
      response of two native tree species, Scots pine and European larch (Larix decidua
      Mill.), and two non-native species, black pine (Pinus nigra Arnold) and Douglas
      fir (Pseudotsuga menziesii Mirb. var. menziesii), to drought. This involved
      analysing how the radial increment of these species responded to increasing water
      shortage (abandonment of irrigation) and to increasingly frequent drought years.
      Black pine and Douglas fir are able to cope with drought better than Scots pine
      and larch, as they show relatively high radial growth even after irrigation has
      been stopped and a plastic growth response to drought years. European larch does
      not seem to be able to cope with these dry conditions as it lacks the ability to
      recover from drought years. The analysis of trees' short-term response to extreme
      climate events seems to be the most promising and suitable method for detecting
      how tolerant a tree species is towards drought. However, combining all the
      methods used in this study provides a complete picture of how water shortage
      could limit species.

PMID- 22363070
TI  - Interactive effects of elevated ozone and temperature on carbon allocation of
      silver birch (Betula pendula) genotypes in an open-air field exposure.
AB  - In the present experiment, the single and combined effects of elevated
      temperature and ozone (O(3)) on four silver birch genotypes (gt12, gt14, gt15 and
      gt25) were studied in an open-air field exposure design. Above- and below-ground
      biomass accumulation, stem growth and soil respiration were measured in 2008. In
      addition, a (13)C-labelling experiment was conducted with gt15 trees. After the
      second exposure season, elevated temperature increased silver birch above- and
      below-ground growth and soil respiration rates. However, some of these variables
      showed that the temperature effect was modified by tree genotype and prevailing
      O(3) level. For instance, in gt14 soil respiration was increased in elevated
      temperature alone (T) and in elevated O(3) and elevated temperature in
      combination (O(3) + T) treatments, but in other genotypes O(3) either partly
      (gt12) or totally nullified (gt25) temperature effects on soil respiration, or
      acted synergistically with temperature (gt15). Before leaf abscission, all
      genotypes had the largest leaf biomass in T and O(3) + T treatments, whereas at
      the end of the season temperature effects on leaf biomass depended on the
      prevailing O(3) level. Temperature increase thus delayed and O(3) accelerated
      leaf senescence, and in combination treatment O(3) reduced the temperature
      effect. Photosynthetic : non-photosynthetic tissue ratios (P : nP ratios) showed
      that elevated temperature increased foliage biomass relative to woody mass,
      particularly in gt14 and gt12, whereas O(3) and O(3) + T decreased it most
      clearly in gt25. O(3)-caused stem growth reductions were clearest in the fastest
      growing gt14 and gt25, whereas mycorrhizal root growth and sporocarp production
      increased under O(3) in all genotypes. A labelling experiment showed that
      temperature increased tree total biomass and hence (13)C fixation in the foliage
      and roots and also label return was highest under elevated temperature. Ozone
      seemed to change tree (13)C allocation, as it decreased foliar (13)C excess
      amount, simultaneously increasing (13)C excess obtained from the soil. The
      present results suggest that warming has potential to increase silver birch
      growth and hence carbon (C) accumulation in tree biomass, but the final magnitude
      of this C sink strength is partly counteracted by temperature-induced increase in
      soil respiration rates and simultaneous O(3) stress. Silver birch populations'
      response to climate change will also largely depend on their genotype
      composition.

PMID- 22363072
TI  - Complications of pancreatic surgery.
AB  - Many diseases, including pancreatitis benign tumors and cancer, may require
      pancreas surgery. Pancreatic resection can lead to a prolonged survival in
      pancreatic cancer and even a potential chance for cure. However, the pancreatic
      surgery can result in complications, and high postoperative morbidity rates are
      still presence. This article reviews the pancreatic abstracts of American
      Pancreas Club 2011, which involves the more common complications, their
      prevention and treatment.

PMID- 22363073
TI  - Pleomorphic adenoma of the lower lip: A review.
AB  - The lower lip is a very rare emerging site for pleomorphic adenoma. The present
      review is to accentuate the definition, frequency, clinical and histopathological
      features, differential diagnosis, prognosis, and treatment choices of pleomorphic
      adenoma. We reviewed the English-language literature addressing pleomorphic
      adenoma of the lower lip. The tumors of minor salivary glands are not frequent
      among whole salivary glands tumors. Pleomorphic adenoma is the most common
      neoplasm among the minor salivary glands. A wide excision is recommended if there
      is no cosmetic care and no risk of damage to the functional structures of head
      and neck. Malignancy of the minor salivary glands are not rare. In addition,
      malignant transformation of pleomorphic adenoma involved in the benign tumors of
      minor salivary glands are possible. Thus, awareness of the possibility of
      existence of a pleomorphic adenoma or a malignant tumor within a mass located on
      the lower lip has a mentionable importance.

PMID- 22363074
TI  - Prevalence, awareness and control of hypertension in estate workers in Malaysia.
AB  - BACKGROUND: Hypertension continues to be a major causative factor contributing to
      cardiovascular, cerebrovascular and renal morbidity and mortality. AIM: The
      objective of this study was to assess the prevalence, awareness and control of
      hypertension in the estate population in Johor, Malaysia. PATIENTS AND METHODS: A
      mercury sphygmomanometer was used to record systolic and diastolic blood
      pressures. Cross sectional population survey was carried out in the study.
      RESULTS: The overall prevalence of hypertension in 903 subjects studied was
      26.91% (243). A higher prevalence 27.65 % (133) was found in males against 26.07%
      (110) in females. Awareness of the disease was present in only 39% (96) of which
      86.45% (83) received treatment. Among those who received treatment, control of
      hypertension was present in 15.66% (13). CONCLUSION: The prevalence of
      hypertension among the estate population is lower than that of the general
      population of Malaysia, which can be attributed to their regular physical
      activity but the awareness, treatment, control and follow-up of patients is
      disappointingly low.

PMID- 22363075
TI  - Urinary tract infection and indirect hyperbilirubinemia in newborns.
AB  - BACKGROUND: Jaundice is a common problem during the neonatal period. About 60% of
      the full term and 80% of premature infants develop jaundice. It can be associated
      with serious illnesses such as Urinary tract infections. AIMS: The aim of this
      study is to evaluate the incidence and prevalence of urinary tract infection in
      newborns with indirect hyperbilirubinemia and to find a relationship with
      prolonged jaundice. PATIENTS AND METHODS: We retrospectively evaluated
      asymptomatic, jaundiced neonates for evidence of a urinary tract infection. Data
      reviewed including demographic and historical data were included with data of
      blood studies, radiological evaluation and treatment. RESULTS: 32 neonates of 152
      cases had urinary tract infection. Most commonly isolated organisms were
      Klebsiella and Escherishia coli. Maximum duration of phototherapy was 4 days in
      the urinary tract infection group versus 7 in the non-urinary tract infection
      group. Intensive phototherapy was used in 18.7% in the urinary tract infection
      group versus 29.16% in the non-urinary tract infection group. None of the
      newborns in the urinary tract infection group underwent exchange transfusion
      therapy. CONCLUSION: Urinary tract infection can occur in asymptomatic, jaundiced
      newborns. Thus, it may be the first in these babies before other signs become
      evident.

PMID- 22363076
TI  - Prevalence of HIV and anemia among pregnant women.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) prevalence is high among rural
      dwellers and pregnant women. AIMS: This study aims to determine the prevalence of
      HIV and anemia among pregnant women attending antenatal clinic in rural community
      of Okada, Edo State, Nigeria. PATIENTS AND METHODS: Anticoagulated blood and sera
      samples were obtained from 480 women consisting of 292 pregnant and 188 non
      pregnant women. Antibodies to HIV were detected in the sera samples and
      hemoglobin concentration of the anticoagulated blood specimens were determined
      using standard techniques. Anemia was defined as hemoglobin concentration <11g/dl
      for pregnant women and <12g/dl for non-pregnant women. RESULTS: Pregnancy was not
      a risk factor for acquiring HIV infection (pregnant vs. non-pregnant: 10.2% vs.
      13.8%; OR=0.713, 95% CI=0.407, 1.259, P = 0.247). The prevalence of HIV was
      significantly (P = 0.005 and P = 0.025) higher in the age group 10-20 years and
      21 - 30 years among pregnant and non-pregnant women respectively. Pregnancy was a
      risk factor for acquiring anemia (OR=1.717, 95% CI=1.179, 2.500, P = 0.006). Only
      the age of pregnant women significantly (P = 0.004) affected the prevalence of
      anemia inversely. CONCLUSION: The prevalence of HIV and anemia among pregnant
      women were 10.2% and 49.3% respectively. Pregnancy was associated with anemia.
      Interventions by appropriate agencies are advocated to reduce associated
      sequelae.

PMID- 22363077
TI  - Noni-based nutritional supplementation and exercise interventions influence body
      composition.
AB  - BACKGROUND: The prevalence of obesity and overweight in the Unites States has
      reached unprecedented levels, and so has the need for effective exercise and
      nutritional programs for prevention of unhealthy weight gain or safe weight loss.
      AIMS: The present study was conducted in overweight men and women to assess the
      impact of noni-based nutritional supplementation and exercise interventions on
      body composition. MATERIALS AND METHODS: Twenty two participants (16 women and 6
      men), ages 18-65, were enrolled in a 12-week, open-label trial of a weight-loss
      program involving noni-based dietary supplements, gender-specific daily calorie
      restriction, and exercise interventions. Weight, percent body fat, and body mass
      index were measured before and after the trial. RESULTS: All participants
      experienced weight loss. The average decrease in fat mass was highly significant
      (P < 0.0001), as were decreases in percent body fat and body mass index.
      Individual weight and fat mass losses were 17.55 +/- 9.73 and 21.78 +/- 8.34
      lbs., respectively, and individual percent body fat and body mass index decreases
      were 8.91 +/- 3.58 % and 2.6 +/- 1.32, respectively. CONCLUSION: The nutritional
      and exercise interventions significantly influenced body composition among
      participants.

PMID- 22363078
TI  - Incidence of temonera, sulphuhydryl variables and cefotaximase genes associated
      with beta-lactamase producing escherichia coli in clinical isolates.
AB  - BACKGROUND: the occurrence of the different types of Extended spectrum beta
      Lactamase producing Escherichia coli with the, Sulphurhydryl variable, Temonera
      and the Cefotaximase have been on the rise AIM: The study was to determine the
      prevalence of extended spectrum beta lactamase gene resistance across the
      clinical isolates of hospitalized patients. MATERIALS AND METHOD: Three hundred
      and fifty isolates of Escherichia coli were received from different clinical
      specimens. The susceptibility profile of the isolates against 10 different
      antibiotics was examined, the MICs (Minimum Inhibitory Concentration) for
      ceftazidime were also determined using micro-broth dilution assay. Isolates
      showing MIC >= 6 MUg/ml for ceftazidime were screened for ESBL (PCT)phenotypic
      confirmatory test and subjected to PCR (polymerase chain reaction) to further.
      RESULTS: By disk diffusion test, there was resistance to ceftazidime and
      cefotaxime were 180(51.4%) and 120 (34.2%) respectively. However, all strains
      were susceptible to imipenem. 250 isolates showed MICs>= 6 MUg/ml for ceftazidime
      of which 180 (72%) were positive for extended spectrum beta lactamase. The
      prevalence of Sulphurhydryl variable, Temonera and the Cefotaximase among these
      isolates were 17.1%, 6.6% and 17%, respectively. CONCLUSION: For the
      identification of extended spectrum beta lactamase producing isolates it is
      recommended that clinical laboratories adopt simple test based on Cinical
      laboratory standard institute recommendation for confirming extended spectrum
      beta lactamase production in enterobacteriacea species.

PMID- 22363079
TI  - Current studies on bacterospermia the leading cause of male infertility: a
      protege and potential threat towards mans extinction.
AB  - BACKGROUND: The current rise of male infertility associated with bacterospermia
      and urogenital infection has been on the increase amongst adult married males in
      Benin metropolis and a major cause of concern to male fertility and reproduction
      in Nigeria. AIM: To microbiologically isolate and study the infectious agent that
      has led to male infertility and also to study the percentage occurrence of
      bacteropsermia and urogenital caused infertility in adult married males in Benin
      metropolis MATERIAL AND METHOD: using standard microbiological methods of
      isolating and identifying the organism, specimen was collected and processed
      which includes the susceptibility profile of isolates and sperm quality. In this
      study a total of 140 sperm samples was collected from patient who were referred
      from the consultant outpatient department of the University of Benin Teaching
      Hospital and then evaluated bacteriologically using standard bacterial cultural
      methods RESULTS: Among the total cases, 92 (65.7%) showed at least one pathogen.
      Staphylococcus aureus (28.3%), Staphylococcus Saprophyticus (13.0%), Pseudomonas
      aerouginosa (6.5%), Escherichia Coli (19.6%) Proteus mirabilis (10.8%) Klebsiella
      spp (10.8%) and Proteus vulgaris (10.8%). CONCLUSION: There was an outstanding
      significant relationship between bacteriospermia and the rate of total motility
      and morphologically abnormal sperms, The percentage of morphologically normal
      sperm was lower in this study. Staphylococcus aureus Staphylococcus saprohyticus
      and Escherichia coli were the most common pathogen having negative effects on
      sperm motility and morphology in this study.

PMID- 22363080
TI  - Urinary tract infections caused by staphylococcus aureus DNA in comparison to the
      candida albicans DNA.
AB  - BACKGROUND: Bacterial DNA released upon bacterial autolysis or killed by
      antibiotics, hence, many inflammatogenic reactions will be established leading to
      serious tissue damage. AIM: the present work aimed to elucidate the
      histopathological changes caused by prokaryotic (bacterial) DNA and eukaryotic
      (candidal) DNA. MATERIALS AND METHODS: twenty one Staphylococcus aureus and 36
      Candida albicans isolates were isolated from UTI patients. Viable cells and DNA
      of the highest antibiotic sensitive isolates were injected, intraurethraly, in
      mice. Results were evaluated via histopathological examination. RESULTS: Mildest
      reactions were obtained from mice challenged with viable C. albicans compared
      with those challenged with viable S. aureus. Dose-dependent histological changes
      were observed for both eukaryotic and prokaryotic DNA. However, the eukaryotic C.
      albicans DNA developed less intense histological changes than S. aureus DNA.
      CONCLUSION: microbial DNA has the ability to cause damage in murine renal system.
      Nevertheless, bacterial DNA caused more intense damage than candidal DNA.

PMID- 22363081
TI  - Pancreatic cancer: Animal model and molecular biology.
AB  - THE ABSTRACT IS AVAILABLE AT THE CLINICAL PANCREATIC DISORDER I: Acute
      pancreatitis. North Am J Med Sci 2011; 3: 316-319. doi: 10.4297/najms.2011.3316.

PMID- 22363082
TI  - Trapezius upper portion trigger points treatment purpose in positional release
      therapy with electromyographic analysis.
AB  - BACKGROUND: This quantification process is made through electromyography
      analysis. This technique of analysis is able to provide a general view of the
      tension decrease in the superior muscle fibers of the trapezius after therapy.
      AIMS: The focus of the present work is to evaluate the treatment of the
      cervicobrachialgia by Positional Release Therapy (PRT). MATERIAL AND METHODS: The
      present work studies six patients, with ages 44 to 63 (1 male and 5 female) who
      present tension in the trapezius upper portion fibers. All patients were
      submitted to 10 session of 30 minutes each. The electromyography was collected on
      the first and tenth day of treatment. RESULTS: The results demonstrated a
      progressive decrease of pain in each session. The tension was evaluated by the
      electromyography analysis, which showed the relations between time of treatment
      and less pain. CONCLUSION: With these results, it was possible to verify
      quantitatively the efficiency of the PRT in the improvement of life quality.

PMID- 22363083
TI  - Efficacy of segmental stabilization exercise for lumbar segmental instability in
      patients with mechanical low back pain: A randomized placebo controlled crossover
      study.
AB  - BACKGROUND: Lumbar segmental stability is an important biomechanical component
      that influences symptoms amongst patients with Mechanical low back pain. AIMS: To
      compare the efficacy of segmental stabilization exercises utilizing multifidus
      and transversus abdominis muscles versus a placebo treatment in patients with
      lumbar segmental instability. MATERIALS AND METHODS: The study was an observer
      blinded randomized placebo-controlled cross-over study of 18 adults (12 men, 6
      women), of mean age 22.5 +/- 1.09 yrs who scored 7/13 in subjective aspects and
      8/14 in objective aspects of Delphi criteria for lumbar segmental instability.
      The selected subjects were then randomized to receive either placebo-control
      (prone lying) or experimental (lumbar segmental stabilization) as a first
      treatment. Each treatment was followed by a wash-out period of 24 hours. Outcomes
      were measured four times- pre- and post- first intervention, pre- and post-
      second intervention. The outcome measures used were pain on Visual analogue
      scale, Pressure pain threshold and Joint play grading scale (0-6 scale) on that
      level. RESULTS: Two-way analysis of variance and post-hoc analysis using
      Bonferonni test were used with level of significance set at p<.05 using
      Statistical package for social sciences version 12.0.1 for Windows. Visual
      analogue scale changed significantly in both the periods of intervention- in
      control (P =.016) and experimental (P =.000) periods. However this improvement
      was more significant in the experimental period. The Joint play grading scale
      scores improved only in the experimental condition compared to the control
      condition significantly. The Pressure pain threshold also improved significantly
      in the experimental condition (P =.000) while the changes in control condition
      was not statistically significant (P=.816). CONCLUSION: Segmental stabilization
      exercise was more effective than placebo intervention in symptomatic lumbar
      segmental instability.

PMID- 22363084
TI  - Prevalence of intestinal parasites among patients of a tertiary hospital in Benin
      city, Nigeria.
AB  - BACKGROUND: Intestinal parasitic infections have been described as constituting
      the greatest single worldwide cause of illness and disease. AIM: The objective of
      this study is to investigate the prevalence of intestinal parasitic infections in
      relation to sex and age as well as seasons of the year in Benin city, Nigeria.
      MATERIALS AND METHODS: The stool samples were processed using saline and iodine
      mounts and examined microscopically for ova and cysts of parasites. RESULTS: The
      overall prevalence of intestinal parasitic infections was 3.9% while gender and
      season had no correlation with the prevalence of intestinal parasites (P = 0.548,
      P = 0.696). There was a significant relationship between intestinal parasitic
      infection and age (P < 0.033). Ascaris lumbricoides was the most prevalent
      (51.4%) while Entamoeba histolytica had the least prevalence (5.4%). CONCLUSION:
      The results of this study concluded that 36 patients were infected with various
      intestinal parasites and that age significantly affected the prevalence of
      parasitic infections. Effective treatment of infected patients and improved
      sanitary habits is advocated.

PMID- 22363085
TI  - Timing of planned caesarean section and the morbidities of the newborn.
AB  - BACKGROUND: Elective caesarean section rates have risen over the last decade
      worldwide. The increase in this rate is not associated with clear benefit for the
      baby or mother but proportionally associated with increased morbidity for both.
      Neonatal adverse outcomes in infants born before 39 weeks of gestation are
      increased and increase progressively as gestational age at birth declines AIM: To
      compare neonatal outcomes of elective caesarean section performed at or beyond
      completed 37 weeks of gestation with >= 38 weeks of gestation. MATERIAL AND
      METHOD: This is a prospective observational study. During the period from July
      2010 through April 2011 a total 134 neonates delivered by elective Cesareans at
      term and were divided into two groups, those who were born (early term) before 38
      weeks of gestation (37+0 - 37+6) and those who were born (late term) at or
      greater than 38 weeks of gestation. We analyzed the following variables sex,
      number of maternal parities, mode of anesthesia, Apgar score at first and fifth
      minute, respiratory complications, hypothermia, hypoglycemia, feeding
      difficulties and admission to neonatal intensive care unit. RESULTS: During the
      period of the study 890 live births whether delivered by Cesarean section or
      normal vaginal delivery. Of these only 134 neonates fulfilling the inclusion
      criteria were included. About 50% of them were delivered before 38 weeks of
      gestation. We performed our analysis on those 134 neonates and we found a
      significant risk in the early Cesareans group in comparison to later group for
      development of respiratory complications (P=0.0001), hypothermia (P=0.0001) and
      feeding difficulty (P=0.0001). CONCLUSION: Significant reduction in the neonatal
      morbidities if the time of elective Cesareans is at completed 38 weeks or beyond
      38 weeks of gestation. Further larger studies are needed to analyze the factors
      responsible for our new date regarding the hypothermia and feeding difficulty in
      neonates born electively by Cesareans before 38 completed weeks of gestation.

PMID- 22363086
TI  - Vitamin D deficiency in a man with multiple myeloma.
AB  - CONTEXT: Vitamin D deficiency is extremely common in multiple myeloma, and it
      represents a surrogate for clinical multiple myeloma disease status. Patients may
      complain of dull, persistent, generalized musculoskeletal aches and pains with
      fatigue or decrease in muscle strength. CASE REPORT: A 63 year old male with
      multiple myeloma on Bortezomib presented with worsening generalized
      musculoskeletal pain, weakness, and multiple falls. On initial examination he was
      pale with a depressed affect. He had resting tremor, generalized bony tenderness,
      worse on movement and weight bearing, muscle weakness, and a waddling gait. His
      bone studies showed features of osteomalacia with a very low Vitamin D level of
      less than 20 nmol/L. He was treated with 3000 units of Vitamin D daily and
      physiotherapy. After 4 months, although his multiple myeloma deteriorated, there
      was a significant decrease in his generalized musculoskeletal pain. CONCLUSIONS:
      This case highlights that vitamin D deficiency is common in patients with
      multiple myeloma, and can cause generalized musculoskeletal pain and increase the
      risk of falls, yet it often goes unrecognized. In patients with non-specific
      musculoskeletal pain, and inadequate sun-exposure medical practitioners must have
      a high index of suspicion for vitamin D deficiency.

PMID- 22363087
TI  - Pseudo-thrombotic thrombocytopenic purpura: A rare presentation of pernicious
      anemia.
AB  - CONTEXT: Schistocytes are fragmented red blood cells due to the flow of blood
      through damaged capillaries and indicate endothelial injury. They are typical of
      microangiopathic hemolytic anemia seen in life threatening conditions like
      disseminated intravascular coagulation or thrombotic thrombocytopenic
      purpura/hemolytic uremic syndrome .We report a rare sub-acute presentation of
      pernicious anemia with hemolysis, thrombocytopenia and numerous schistocytes that
      was initially diagnosed as a more serious thrombotic thrombocytopenic purpura.
      CASE REPORT: A 31-year-old Caucasian woman presented with fatigue and paresthesia
      of both feet for 1 week. Past medical history included hypertension and gastro
      esophageal reflux disease. Examination revealed scleral icterus and pallor.
      Examination of the abdomen did not show hepatosplenomegaly. Initial laboratory
      tests showed severe anemia, and low platelets. Indirect bilirubin and serum
      Lactate De Hydrogenase were elevated. Prothrombin time, partial thromboplastin
      time, serum fibrinogen, and serum fibrin degradation product levels were normal.
      Peripheral smear revealed numerous schistocytes, anisocytosis and macro
      ovalocytes. Thrombotic thrombocytopenic purpura (TTP) was suspected due to the
      constellation of sub-acute onset of fatigue and paresthesia along with
      thrombocytopenia, schistocytes and an elevated LDH. Plasmapheresis was initiated
      for possible TTP. However, platelet count worsened despite plasmapheresis for 4
      days. On re-evaluation, vitamin B(12) was found to be low. Treatment with intra
      muscular vitamin B(12) led to symptomatic and hematologic improvement. Pernicious
      anemia was confirmed by the presence of anti-intrinsic factor antibodies,
      elevated serum gastrin level and atrophic gastritis. CONCLUSION: Clinicians must
      be aware of unusual clinical presentation of vitamin B(12) deficiency with
      schistocytes as the management is simple and effective.

PMID- 22363088
TI  - HAM56 and CD68 antigen presenting cells surrounding a sarcoidal granulomatous
      tattoo.
AB  - CONTEXT: Tattoos are produced by introducing colorants of various compositions
      into the skin, either accidentally or for cosmetic purposes. CASE REPORT: A 62
      year-old male presented with a cosmetic tattoo and requested a total excision of
      the lesion. Dermatopathologic analysis of the excised tissue with hematoxylin and
      eosin examination, as well as immunohistochemistry was performed. H&E staining
      demonstrated classic histologic features of a tattoo. Utilizing
      immunohistochemistry, dermal histiocytic antigen presenting cells stained with
      HAM56 and CD68 antibodies; the staining was present surrounding the tattoo
      pigment. CONCLUSIONS: We identified two macrophage markers (HAM56 and CD68)
      surrounding dermal tattoo pigment. A minimal dermal inflammatory immune was noted
      to the tattoo pigment. Moreover, the immune response and/or tolerance to tattoos
      is not well characterized. We suggest that tattoo materials and techniques could
      be utilized in therapeutic delivery for diseases such recessive dystrophic
      epidermolysis bullosa, potentially preventing immune rejection of gene therapy
      agents.

PMID- 22363089
TI  - Comparison of real-time SYBR green dengue assay with real-time taqman RT-PCR
      dengue assay and the conventional nested PCR for diagnosis of primary and
      secondary dengue infection.
AB  - BACKGROUND: Dengue fever and dengue hemorrhagic fever are caused by dengue virus.
      Dengue infection remains a burning problem of many countries. To diagnose acute
      dengue in the early phase we improve the low cost, rapid SYBR green real time
      assay and compared the sensitivity and specificity with real time Taqman((r))
      assay and conventional nested PCR assay. AIMS: To develop low cost, rapid and
      reliable real time SYBR green diagnostic dengue assay and compare with Taqman
      real-time assay and conventional nested PCR (modified Lanciotti). MATERIALS AND
      METHODS: Eight cultured virus strains were diluted in tenth dilution down to
      undetectable level by the PCR to optimize the primer, temperature (annealing, and
      extension and to detect the limit of detection of the assay. Hundred and ninety
      three ELISA and PCR proved dengue clinical samples were tested with real time
      SYBR((r)) Green assay, real time Taqman((r)) assay to compare the sensitivity and
      specificity. RESULTS: Sensitivity and specificity of real time SYBR(r) green
      dengue assay (84% and 66%, respectively) was almost comparable to those (81% and
      74%) of Taqman real time PCR dengue assay. Real time SYBR((r)) green RT-PCR was
      equally sensitive in primary and secondary infection while real time Taqman was
      less sensitive in the secondary infection. Sensitivity of real time Taqman on
      DENV3 (87%) was equal to SYBR green real time PCR dengue assay. CONCLUSION: We
      developed low cost rapid diagnostic SYBR green dengue assay. Further study is
      needed to make duplex primer assay for the serotyping of dengue virus.

PMID- 22363090
TI  - A novel use of endoscopic cutter: Endoscopic retrieval of a retained nasogastric
      tube following a robotically assisted laparoscopic biliopancreatic diversion with
      duodenal switch.
AB  - CONTEXT: A nasogastric tube is utilized routinely by many bariatric surgeons to
      assist creation of gastrojejunal anastomosis during roux-en-y gastric bypass or
      duodenojejunal anastomosis during biliopancreatic diversion. However, inadvertent
      stapling or suturing of the nasogastric tube has been known as a potential
      complication of this technique. CASE REPORT: We describe a successful endoscopic
      removal of an inadvertently sutured nasogastric tube at the level of the
      duodenojejunal anastomosis in a 30-year-old woman undergoing a robotically
      assisted laparoscopic biliopancreatic diversion with duodenal switch for super
      morbid obesity. CONCLUSIONS: Endoscopic technique is a feasible and safe
      minimally invasive technique to release a retained nasogastric tube with
      preservation of the newly created anastomosis. This option gives major advantages
      of avoiding a re-operation, as well as the potential general anesthetic
      complications.

PMID- 22363091
TI  - Sample size formulae for two-stage randomized trials with survival outcomes.
AB  - Two-stage randomized trials are growing in importance in developing adaptive
      treatment strategies, i.e. treatment policies or dynamic treatment regimes.
      Usually, the first stage involves randomization to one of the several initial
      treatments. The second stage of treatment begins when an early nonresponse
      criterion or response criterion is met. In the second-stage, nonresponding
      subjects are re-randomized among second-stage treatments. Sample size
      calculations for planning these two-stage randomized trials with failure time
      outcomes are challenging because the variances of common test statistics depend
      in a complex manner on the joint distribution of time to the early nonresponse
      criterion or response criterion and the primary failure time outcome. We produce
      simple, albeit conservative, sample size formulae by using upper bounds on the
      variances. The resulting formulae only require the working assumptions needed to
      size a standard single-stage randomized trial and, in common settings, are only
      mildly conservative. These sample size formulae are based on either a weighted
      Kaplan-Meier estimator of survival probabilities at a fixed time-point or a
      weighted version of the log-rank test.

PMID- 22363092
TI  - Psychometric Validation of the Sexual Function Questionnaire in Poland.
AB  - Questionnaires diagnosing sexual dysfunctions in women are important tools which
      can facilitate the diagnosis and therapy of individual female patients. The study
      is aimed at the adaptation of the Sexual Function Questionnaire, which was
      designed by Frances H. Quirk and associates for the American population, to
      Polish conditions (Quirk et al. in J Sex Med 4:469-77, 1). The study group
      consisted of 143 women aged 20-68 who were receiving gynaecological care and
      displayed various types of sexual dysfunction (e.g. female sexual arousal
      disorder, female orgasmic disorder, dyspareunia), or none of those. The good
      psychometric quality of the Sexual Function Questionnaire has been confirmed with
      the following results: convergent validity r(s)=0.62, p<0.01, construct validity
      was estimated by Principal Component Analysis with the promax rotation method.
      The 7 factors together explained 80.7% of total variance, and a reliability of
      0.97 for the whole test, with that for particular domains ranging from 0.62 to
      0.96 (estimated with Cronbach's alpha). The obtained results are mostly
      consistent with results from studies conducted by the authors of the
      Questionnaire in the United States, and with the adaptation study carried out in
      Iran. There are, however, some differences in the assignment of questions to
      particular domains, as well as in the names of the domains.

PMID- 22363093
TI  - An evidence-based approach to the assessment of heart-type Fatty Acid binding
      protein in acute coronary syndrome.
AB  - Cardiac troponins have been the biomarkers of choice for the diagnosis of acute
      coronary syndrome (ACS) for over a decade. There has, however, been considerable
      interest over the last two decades for newer biomarkers that would bring added
      value to the measurement of troponin such as the provision of prognosis and
      assistance in the choice of therapeutic interventions. In this manuscript, we
      review the development of heart-type fatty acid binding protein (H-FABP) in
      patients with ACS using the evidence-based laboratory medicine format.Phase I
      studies have established that H-FABP reference intervals and pre-analytical
      factors influencing H-FABP. Phase II studies have confirmed a) that H-FABP is
      elevated in patients with established myocardial infarction; b) that its serum
      concentration is related to the extent of infarction using survival as a
      surrogate; and c) that its use in chest pain patients can identify ACS patients
      and also provide prognostic information on survival. Furthermore, it is an
      independent prognostic marker for patients with suspected ACS who are troponin
      negative. Phase III studies involving randomised control trials for diagnosis and
      prognosis have not yet been performed and Phase IV studies await uptake of H-FABP
      in a routine service.

PMID- 22363094
TI  - Evidence-based laboratory medicine: is it working in practice?
AB  - The principles of Evidence-Based Medicine have been established for about two
      decades, with the need for evidence-based clinical practice now being accepted in
      most health systems around the world. These principles can be employed in
      laboratory medicine. The key steps in evidence-based practice, namely (i)
      formulating the question; (ii) searching for evidence; (iii) appraising evidence;
      (iv) applying evidence; and (v) assessing the experience are all accepted but, as
      yet, translation into daily clinical and laboratory practice has been slow.
      Furthermore, the demand for evidence-based laboratory medicine (EBLM) has been
      slow to develop.There are many contrasting observations about laboratory
      medicine, for example (i) there is too much testing vs insufficient testing; (ii)
      testing is expensive vs laboratories are expected to generate income; and (iii)
      test results have little impact on outcomes vs test results are crucial to
      clinical decision making. However, there is little evidence to support any of
      these observations. Integrating the principles of EBLM into routine practice will
      help to resolve some of these issues by identifying (a) where laboratory medicine
      fits into the care pathway; (b) where testing is appropriate; (c) the nature and
      quality of evidence required to demonstrate the clinical utility of a test; (d)
      how the test result impacts on clinical actions; (e) where changes in the care
      pathway will occur; and (f) where benefit/value can be achieved. These answers
      will help to establish the culture of EBLM in clinical and laboratory practice.

PMID- 22363095
TI  - Reporting of Genetic Variants by Diagnostic Laboratories and other Centres.

PMID- 22363096
TI  - A model of care for familial hypercholesterolaemia: key role for clinical
      biochemistry.
AB  - Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present
      from birth that causes marked elevation in plasma low-density lipoprotein (LDL)
      cholesterol concentrations and premature coronary heart disease. There are at
      least 45,000 people with FH in Australia and New Zealand, but most remain
      unrecognised and those diagnosed remain inadequately treated. To bridge this gap
      in coronary prevention the FH Australasia Network has developed a model of care
      for FH. An executive summary of the model of care is presented, with a commentary
      on its recommendations and the key role of the clinical biochemistry laboratory.

PMID- 22363097
TI  - Antioxidants of therapeutic relevance in COPD from the neotropical blueberry
      Anthopterus wardii.
AB  - Four flavone C-glycosides, isoorientin (1), orientin (2), vitexin (3), and
      isovitexin (4), were isolated from the neotropical blueberry of Anthopterus
      wardii, a so-called "superfruit", using antioxidant activity-guided
      fractionation. A dose-response relationship of compounds 1-4 was determined for
      their anti-inflammatory activity against interleukin-8 (IL-8) and for the
      inhibition of matrix metalloproteinase-1 (MMP-1) expression, an inflammatory
      marker for chronic obstructive pulmonary disease. The four flavone C-glycosides
      exhibited inhibitory activity against IL-8 production and MMP-1 expression, with
      compounds 1, 3, and 4 having the most potent inhibitory activities in both assays
      at 100 MUg/ml. The structures of compounds 1-4 were determined by spectroscopic
      methods. These flavone C-glycosides are reported for the first time in the
      Anthopterus genus.

PMID- 22363098
TI  - Dimensionality Analysis of the Thought Suppression Inventory: Combining EFA, MSA,
      and CFA.
AB  - The Thought Suppression Inventory (TSI; Rassin, European Journal of Personality
      17: 285-298, 2003) was designed to measure thought intrusion, thought suppression
      and successful thought suppression. Given the importance to distinguish between
      these three aspects of thought control, the aim of this study was to scrutinize
      the dimensionality of the TSI. In a sample of 333 Dutch senior citizins, we
      examined (1) the dimensionality of the TSI using various procedures such as PAF,
      Mokken scale analysis (MSA) and CFA, and (2) the scale properties of the TSI. PAF
      favored a two factor solution, however, MSA and CFA suggested that three
      dimensions most adequately capture the structure of the TSI. Although all scales
      obtained at least medium scalability coefficients, several items were identified
      that are psychometrically unsound and may benefit from rewording or replacement.
      The findings suggest that the TSI is a three-dimensional questionnaire as
      originally proposed by Rassin (European Journal of Personality 17: 285-298, 2003)
      measuring thought intrusion, thought suppression, and successful thought
      suppression.

PMID- 22363099
TI  - Factors Relating to Managerial Stereotypes: The Role of Gender of the Employee
      and the Manager and Management Gender Ratio.
AB  - PURPOSE: Several studies have shown that the traditional stereotype of a "good"
      manager being masculine and male still exists. The recent changes in the
      proportion of women and female managers in organizations could affect these two
      managerial stereotypes, leading to a stronger preference for feminine
      characteristics and female leaders. This study examines if the gender of an
      employee, the gender of the manager, and the management gender ratio in an
      organization are related to employees' managerial stereotypes. 
      DESIGN/METHODOLOGY/APPROACH: 3229 respondents working in various organizations
      completed an electronic questionnaire.  FINDINGS: The results confirm our
      hypotheses that, although the general stereotype of a manager is masculine and
      although most prefer a man as a manager, female employees, employees with a
      female manager, and employees working in an organization with a high percentage
      of female managers, have a stronger preference for feminine characteristics of
      managers and for female managers. Moreover, we find that proximal variables are
      much stronger predictors of these preferences than more distal variables. 
      IMPLICATIONS: Our study suggests that managerial stereotypes could change as a
      result of personal experiences and changes in the organizational context. The
      results imply that increasing the proportion of female managers is an effective
      way to overcome managerial stereotyping.  ORIGINALITY/VALUE: This study examines
      the influence on managerial stereotypes of various proximal and distal factors
      derived from theory among a large group of employees (in contrast to students).

PMID- 22363100
TI  - Being Successful in a Creative Profession: The Role of Innovative Cognitive
      Style, Self-Regulation, and Self-Efficacy.
AB  - PURPOSE: The purpose of this study was to test a model that proposes that
      innovative cognitive style and self-regulation (setting priorities, planning work
      activities, and monitoring time and task progress) are related to the self
      reported success of architects. We investigated two aspects of the success: as
      designers and as business people. To this end, we examined the mediating role of
      self-efficacy in these relationships.  DATA/METHODOLOGY/APPROACH: We collected
      data using a web-based survey among 276 architects in the Netherlands. These were
      architects that either managed and/or owned a company, including freelance
      architects.  FINDINGS: Innovative cognitive style was related directly and
      indirectly, via design self-efficacy, to the self-rating of being a successful
      designer. Self-regulation, via self-efficacy, was indirectly related to being a
      successful designer, and directly related to being a successful businessperson.
      In addition, design success was related to success as a businessperson. 
      IMPLICATIONS: This study shows that self-regulation at work is related to self
      rated success in design and business. We regard self-regulation to be a form of
      actively managing work tasks, identified as an increasingly important type of
      behavior at work.  ORIGINALITY/VALUE: This study is one of the first to
      investigate the self-regulation of creative professionals that included both
      design and business aspects. We focused on three aspects of self-regulation, and
      tested our model using structural equation modeling.

PMID- 22363101
TI  - Distinct proteasome subpopulations in the alveolar space of patients with the
      acute respiratory distress syndrome.
AB  - There is increasing evidence that proteasomes have a biological role in the
      extracellular alveolar space, but inflammation could change their composition. We
      tested whether immunoproteasome protein-containing subpopulations are present in
      the alveolar space of patients with lung inflammation evoking the acute
      respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants
      and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10)
      were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and
      proteasome subtypes by western blot, chromatographic purification, and 2D
      dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects
      LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled
      ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography
      revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of
      ARDS patients that differed from healthy subjects. Total proteasome concentration
      in BAL supernatant was increased in ARDS (971 ng/mL +/- 1116 versus 59 +/- 25; P
      < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser
      extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the
      first time immunoproteasome proteins and a distinct proteasomal subtype pattern
      in the alveolar space of ARDS patients, presumably in response to inflammation.

PMID- 22363102
TI  - Human mast cells (HMC-1 5C6) enhance interleukin-6 production by quiescent and
      lipopolysaccharide-stimulated human coronary artery endothelial cells.
AB  - We examined the effect of intact human mast cells (HMC-1 5C6) and their selected
      mediators on interleukin-6 (IL-6) production and bone morphogenetic protein-2
      (BMP-2) expression in human coronary artery endothelial cells (HCAEC) in the
      presence and absence of lipopolysaccharide (LPS). Scanning electron microscopy
      showed that HMC-1 5C6 cells adhere to HCAEC in cocultures. Addition of HMC-1 5C6
      cells markedly enhanced the IL-6 production by quiescent and LPS-activated HCAEC
      even at the maximal concentration of LPS. Furthermore, mast cell-derived
      histamine and proteases accounted for the direct and synergistic effect of mast
      cells on IL-6 production that was completely blocked by the combination of
      histamine receptor-1 antagonist and protease inhibitors. Another novel finding is
      that histamine was able to induce BMP-2 expression in HCAEC. Collectively, our
      results suggest that endotoxin and mast cell products synergistically amplify
      vascular inflammation and that histamine participates in the early events of
      vascular calcification.

PMID- 22363103
TI  - Low dose theophylline showed an inhibitory effect on the production of IL-6 and
      IL-8 in primary lung fibroblast from patients with COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by the abnormal and
      chronic lung inflammation. We hypothesized that lung fibroblasts could contribute
      to the local inflammation and investigated whether low dose theophylline had a
      beneficial effect on fibroblasts inflammation. Subjects undergoing lobectomy for
      bronchial carcinoma were enrolled and divided into COPD and control groups
      according to spirometry. Primary human lung fibroblasts were cultured from
      peripheral lung tissue distant to tumor tissue. There was a significant increase
      in both the mRNA expressions and protein levels for IL-6 and IL-8 in fibroblasts
      in COPD group, and the values were negatively correlated with lung function (P <
      0.05). For COPD fibroblasts, the protein levels of IL-6 and IL-8 decreased from
      993.0 +/- 738.9 pg/mL to 650.1 +/- 421.9 pg/mL (P = 0.014) and from 703.1 +/-
      278.0 pg/mL to 492.0 +/- 214.9 pg/mL (P = 0.001), respectively, with 5 MUg/mL
      theophylline treatment. In addition, theophylline at the dose of 5 MUg/mL reduced
      the increased production of IL-6 and IL-8 induced by 1 MUg/mL LPS in primary
      human lung fibroblasts. Our data suggest that lung fibroblasts participate in the
      chronic inflammation in COPD by releasing IL-6 and IL-8, and low dose
      theophylline can alleviate the proinflammatory mediators' production by
      fibroblasts.

PMID- 22363105
TI  - Will MR image-guided brachytherapy be a standard of care for cervical cancer in
      future? An Indian perspective.

PMID- 22363104
TI  - Role of macrophage migration inhibitory factor in the proliferation of smooth
      muscle cell in pulmonary hypertension.
AB  - Pulmonary hypertension (PH) contributes to the mortality of patients with lung
      and heart diseases. However, the underlying mechanism has not been completely
      elucidated. Accumulating evidence suggests that inflammatory response may be
      involved in the pathogenesis of PH. Macrophage migration inhibitory factor (MIF)
      is a critical upstream inflammatory mediator which promotes a broad range of
      pathophysiological processes. The aim of the study was to investigate the role of
      MIF in the pulmonary vascular remodeling of hypoxia-induced PH. We found that MIF
      mRNA and protein expression was increased in the lung tissues from hypoxic
      pulmonary hypertensive rats. Intensive immunoreactivity for MIF was observed in
      smooth muscle cells of large pulmonary arteries (PAs), endothelial cells of small
      PAs, and inflammatory cells of hypoxic lungs. MIF participated in the hypoxia
      induced PASMCs proliferation, and it could directly stimulate proliferation of
      these cells. MIF-induced enhanced growth of PASMCs was attenuated by MEK and JNK
      inhibitor. Besides, MIF antagonist ISO-1 suppressed the ERK1/2 and JNK
      phosphorylation induced by MIF. In conclusion, the current finding suggested that
      MIF may act on the proliferation of PASMCs through the activation of the ERK1/2
      and JNK pathways, which contributes to hypoxic pulmonary hypertension.

PMID- 22363106
TI  - Dose linearity and monitor unit stability of a G4 type cyberknife robotic
      stereotactic radiosurgery system.
AB  - Dose linearity studies on conventional linear accelerators show a linearity error
      at low monitor units (MUs). The purpose of this study was to establish the dose
      linearity and MU stability characteristics of a cyberknife (Accuray Inc., USA)
      stereotactic radiosurgery system. Measurements were done at a depth of 5 cm in a
      stereotactic dose verification phantom with a source to surface distance of 75 cm
      in a Generation 4 (G4) type cyberknife system. All the 12 fixed-type collimators
      starting from 5 to 60 mm were used for the dose linearity study. The dose
      linearity was examined in small (1-10), medium (15-100) and large (125-1000) MU
      ranges. The MU stability test was performed with 60 mm collimator for 10 MU and
      20 MU with different combinations. The maximum dose linearity error of -38.8% was
      observed for 1 MU with 5 mm collimator. Dose linearity error in the small MU
      range was considerably higher than in the medium and large MU ranges. The maximum
      error in the medium range was -2.4%. In the large MU range, the linearity error
      varied between -0.7% and 1.2%. The maximum deviation in the MU stability was 
      3.03%.

PMID- 22363107
TI  - Quantitative comparison of volumetric modulated arc therapy and intensity
      modulated radiotherapy plan quality in sino-nasal cancer.
AB  - The aim of this study was to compare various dosimetric parameters of dynamic mlc
      intensity modulated radiotherapy (IMRT) plans with volumetric modulated arc
      therapy (VMAT) plans for sino-nasal cancers, which are rare and complex tumors to
      treat with radiotherapy. IMRT using five fields, coplanar in the sagittal plane
      and VMAT employing two coplanar arc plans were created for five patients. The
      plans were assessed by comparing Conformity Index and Sigma Index (dose
      homogeneity) in the Planning Target Volume (PTV) and through comparison of dose
      volume characteristics to the following organs at risk (OARs): Spinal cord,
      brainstem, eye, ipsilateral and contralateral optic nerve and the volume of brain
      receiving 10% of the prescribed dose (V(10%)). The total monitor units required
      to deliver the plan were also compared. Conformity Index was found to be superior
      in VMAT plans for three patients and in IMRT plans for two patients. Dose
      homogeneity within the PTV was better with VMAT plans for all five cases. The
      mean difference in Sigma Index was 0.68%. There was no significant difference in
      dose between IMRT and VMAT plans for any of the OARs assessed in these patients.
      The monitor units were significantly reduced in the VMAT plan in comparison to
      the IMRT plan for four out of five patients, with mean reduction of 66%. It was
      found in this study that for the treatment of sino-nasal cancer, VMAT produced
      minimal, and statistically insignificant improvement in dose homogeneity within
      the PTV when compared with IMRT. VMAT plans were delivered using significantly
      fewer monitor units. We conclude in this study that VMAT does not offer
      significant improvement of treatment for sino-nasal cancer over the existing IMRT
      techniques, but the findings may change with a larger sample of patients in this
      rare condition.

PMID- 22363108
TI  - Evaluation of relative transmitted dose for a step and shoot head and neck
      intensity modulated radiation therapy using a scanning liquid ionization chamber
      electronic portal imaging device.
AB  - The dose delivery verification for a head and neck static intensity modulated
      radiation therapy (IMRT) case using a scanning liquid ionization chamber
      electronic portal imaging device (SLIC-EPID) was investigated. Acquired
      electronic portal images were firstly converted into transmitted dose maps using
      an in-house developed method. The dose distributions were then compared with
      those calculated in a virtual EPID using the Pinnacle(3) treatment planning
      system (TPS). Using gamma evaluation with the DeltaD(max) and DTA criteria of
      3%/2.54 mm, an excellent agreement was observed between transmitted dose measured
      using SLIC-EPID and that calculated by TPS (gamma score approximately 95%) for
      large MLC fields. In contrast, for several small subfields, due to SLIC-EPID
      image blurring, significant disagreement was found in the gamma results.
      Differences between EPID and TPS dose maps were also observed for several parts
      of the radiation subfields, when the radiation beam passed through air on the
      outside of tissue. The transmitted dose distributions measured using portal
      imagers such as SLIC-EPID can be used to verify the dose delivery to a patient.
      However, several aspects such as accurate calibration procedure and imager
      response under different conditions should be taken into the consideration. In
      addition, SLIC-EPID image blurring is another important issue, which should be
      considered if the SLIC-EPID is used for clinical dosimetry verification.

PMID- 22363109
TI  - Determination of the tissue inhomogeneity correction in high dose rate
      Brachytherapy for Iridium-192 source.
AB  - In Brachytherapy treatment planning, the effects of tissue heterogeneities are
      commonly neglected due to lack of accurate, general and fast three-dimensional
      (3D) dose-computational algorithms. In performing dose calculations, it is
      assumed that the tumor and surrounding tissues constitute a uniform, homogeneous
      medium equivalent to water. In the recent past, three-dimensional computed
      tomography (3D-CT) based treatment planning for Brachytherapy applications has
      been popularly adopted. However, most of the current commercially available
      planning systems do not provide the heterogeneity corrections for Brachytherapy
      dosimetry. In the present study, we have measured and quantified the impact of
      inhomogeneity caused by different tissues with a 0.015 cc ion chamber.
      Measurements were carried out in wax phantom which was employed to measure the
      heterogeneity. Iridium-192 ((192)Ir) source from high dose rate (HDR)
      Brachytherapy machine was used as the radiation source. The reduction of dose due
      to tissue inhomogeneity was measured as the ratio of dose measured with different
      types of inhomogeneity (bone, spleen, liver, muscle and lung) to dose measured
      with homogeneous medium for different distances. It was observed that different
      tissues attenuate differently, with bone tissue showing maximum attenuation value
      and lung tissue resulting minimum value and rest of the tissues giving values
      lying in between those of bone and lung. It was also found that inhomogeneity at
      short distance is considerably more than that at larger distances.

PMID- 22363110
TI  - Evaluation of off-axis wedge correction factor using diode dosimeters for
      estimation of delivered dose in external radiotherapy.
AB  - An in vivo dosimetry system, using p-type diode dosimeters, was characterized for
      clinical applications of treatment machines ranging in megavoltage energies. This
      paper investigates two different models of diodes for externally wedged beams and
      explains a new algorithm for the calculation of the target dose at various tissue
      depths in external radiotherapy. The values of off-axis wedge correction factors
      were determined at two different positions in the wedged (toward the thick and
      thin edges) and in the non-wedged directions on entrance and exit surfaces of a
      polystyrene phantom in (60)Co and 6 MV photon beams. Depth transmission was
      defined on the entrance and exit surfaces to obtain the off-axis wedge correction
      factor at any depth. As the sensitivity of the diodes depends on physical
      characteristics [field size, source-skin distance (SSD), thickness, backscatter],
      correction factors were applied to the diode reading when measuring conditions
      different from calibration situations. The results indicate that needful
      correction factors for (60)Co wedged photons are usually larger than those for 6
      MV wedged photon beams. In vivo dosimetry performed with the proposed algorithms
      at externally wedged beams has negligible probable errors (less than 0.5&) and is
      a reliable method for patient dose control.

PMID- 22363112
TI  - A new method to correct the attenuation map in simultaneous transmission/emission
      tomography using Gd/Ga radioisotopes.
AB  - Reconstruction of the tomographic images without attenuation correction can cause
      erroneously high count densities and reduced image contrast in low attenuation
      regions. In order to solve the problem of photon attenuation, one needs to know
      the attenuation coefficient for the individual patient being studied. Therefore,
      we made an attempt to correct the attenuation map in simultaneous
      transmission/emission tomography with (153)Gd/(67)Ga using maximum likelihood
      method using the expectation maximization (ML-EM) algorithm to correct the
      transmission window for both the spillover and downscatter. Spillover fraction,
      scatter fraction and parameters for the scatter function (A, b and c) were
      determined experimentally and optimized using the optimization program written in
      IDL based on simplex theory. All measurements were performed on a Vertex gamma
      camera using the anthropomorphic thorax phantom for validation of data obtained
      by the proposed method. It was observed that without spillover and downscatter
      correction, the mean counts were 19.29 in liver and 26.90 in lung, whereas after
      after applying the corrections, the mean counts were reduced to 3.80 and 15.10 in
      liver and lung, respectively, which were close to true mean counts (liver 2.15
      and lung 14.89). In this proposed method, we introduced the set of
      F(t)(spillover) and K(t)(downscatter) to account for the variations in projection
      pixels (f(t) and k(t)) with the density and thickness. The F(t) and K(t) were
      determined using the transmission data by an iterative process. The quantitative
      error was reduced by 98.0% for lung and 90.0% for liver when the corrected
      transmission images were obtained after the subtraction of spillover and
      downscatter fraction.

PMID- 22363111
TI  - Light sensitometry of mammography films at varying development temperatures and
      times.
AB  - Kodak MinR-2000 mammography film is widely used for mammography imaging. The
      sensitometric indices like base plus fog level (B + F), maximum optical density
      (OD(max)), average gradient (AG) and speed of this film at varying development
      temperatures and times were evaluated using a light sensitometer. Totally 33 film
      strips were cut from a single Kodak MinR-2000 mammography film box and exposed in
      a light sensitometer operated in the green light spectrum to produce a 21-step
      sensitometric strip. These exposed film strips were processed at temperatures in
      the range of 32 degrees C-37 degrees C in the step of 1 degrees C and at
      processing times in the range of 1-6 minutes in the step of 1 minute. The results
      of the present study show that the measured base plus fog level of the
      mammography film was not affected much, whereas significant changes were seen in
      the OD(max), AG and speed with varying development temperatures and times. The
      OD(max) values of the film were found in the range of 3.67-3.76, AG values were
      in the range of 2.48-3.4 and speed values were in the range of 0.015-0.0236 when
      the processing temperature was varied from 32 degrees C to 37 degrees C. With
      processing time variation from 1 to 6 minutes, the observed changes in OD(max)
      values were in the range of 3.54-3.71, changes in AG were in the range of 2.66
      3.27 and changes in speed were in the range of 0.011-0.025. Based on these
      observations, recommendations for optimum processing parameters to be used for
      this film are made.

PMID- 22363113
TI  - Specific activities of natural rocks and soils at quaternary intraplate volcanism
      north of Sana'a, Yemen.
AB  - The level of natural radioactivity in rocks and soil of 32 samples collected from
      locations at North Sana'a in Yemen was measured. Concentrations of radionuclides
      in rocks and soils samples were determined by gamma-ray spectrometer using high
      purity germanium (HPGe) detector with specially designed shield. The average
      radioactivity concentrations of (226)Ra, (232)Th, (40)K were determined and
      expressed in Bq/kg. The results showed that these radionuclides were present in
      concentrations of 21.79 +/- 3.1, 19.5 +/- 2.6 and 399.3 +/- 16 Bq/kg,
      respectively, for rocks. For soil, the corresponding values were 48.2 +/- 4.4,
      41.7 +/- 4.5 and 939.1 +/- 36 Bq/kg, respectively. Also, the radiological hazard
      of the natural radionuclide content, radium equivalent activity, total dose
      rates, external hazard index and gamma activity concentration index of the
      (rocks/soils) samples in the area under consideration were calculated. The dose
      rates at 1 m above the ground from terrestrial sources were 38.39 and 86.89 nGy/h
      for rocks and surface soil, respectively, which present no significant health
      hazards to humans.

PMID- 22363114
TI  - Endoscopic ultrasound-guided biliary drainage.
AB  - Endoscopic ultrasound (EUS)-guided biliary drainage has emerged as a minimally
      invasive alternative to percutaneous and surgical interventions for patients with
      biliary obstruction who had failed endoscopic retrograde cholangiopancreatography
      (ERCP). EUS-guided biliary drainage has become feasible due to the development of
      large channel curvilinear therapeutic echo-endoscopes and the use of real-time
      ultrasound and fluoroscopy imaging in addition to standard ERCP devices and
      techniques. EUS-guided biliary drainage is an attractive option because of its
      minimally invasive, single step procedure which provides internal biliary
      decompression. Multiple investigators have reported high success and low
      complication rates. Unfortunately, high quality prospective data are still
      lacking. We provide detailed review of the use of EUS for biliary drainage from
      the perspective of practicing endoscopists with specific focus on the technical
      aspects of the procedure.

PMID- 22363115
TI  - Targeted systemic therapies for hepatocellular carcinoma: clinical perspectives,
      challenges and implications.
AB  - Hepatocellular carcinoma (HCC) is a lethal disease in most patients, due to its
      aggressive course and a lack of effective systemic therapies for advanced
      disease. Surgical resection and liver transplantation remain the only curative
      options for a small subset of patients. Few patients with HCC are diagnosed early
      enough to be eligible for curative treatment. Angiogenesis inhibition is a
      natural therapeutic target for all solid tumors, but particularly for the highly
      vascularized HCC tumors. With the approval of the targeted agent sorafenib, there
      are now additional options for patients with HCC. Although sorafenib does produce
      some improvement in survival in HCC patients, the responses are not durable. In
      addition, there are significant dermatologic, gastrointestinal, and metabolic
      toxicities, and, as importantly, there is still limited knowledge of its
      usefulness in special subpopulations with HCC. Other angiogenesis inhibitors are
      in development to treat HCC both in the first-line setting and for use following
      sorafenib failure; the furthest in development is brivanib, a dual fibroblast
      growth factor pathway and vascular endothelial growth factor receptor inhibitor.
      Additional agents with antiangiogenic properties also in phase II and III
      development for the treatment of patients with HCC include bevacizumab,
      ramucirumab, ABT-869, everolimus and ARQ 197.

PMID- 22363117
TI  - Seroprevalence of Helicobacter pylori in female Vietnamese immigrants to Korea.
AB  - AIM: To investigate the seroprevalence of Helicobacter pylori (H. pylori) and its
      relationship to nutritional factors in female Vietnamese immigrants to Korea.
      METHODS: A total of 390 female immigrants from Vietnam and 206 Korean male
      spouses participated in the study. Blood samples from 321 female immigrants and
      201 Korean male spouses were analyzed for H. pylori antibodies. Data on age, sex,
      alcohol consumption, smoking status, dietary nutritional factors and
      gastrointestinal symptoms were collected using questionnaires. The daily intakes
      of the following nutrients were estimated: energy, protein, niacin, lipid, fiber,
      calcium, iron, sodium, potassium, zinc, folate, cholesterol, and vitamins A, B1,
      B2, B6, C and E. RESULTS: The prevalence of H. pylori positivity was lower in the
      immigrants than in age-matched Korean females (55.7% vs 71.4%, respectively; P <
      0.0001) and the domestic population of Vietnam. The prevalence of H. pylori
      positivity among married couples was 31.7% for both spouses. There were no
      statistically significant differences in the incidence of smoking, amount of
      alcohol consumed, or nutritional factors between the H. pylori-positive and
      negative groups. CONCLUSION: The prevalence of H. pylori positivity was lower
      among female Vietnamese immigrants than among Korean females. Nutritional factors
      did not differ between the H. pylori-positive and negative groups.

PMID- 22363116
TI  - Dynamic tracking of stem cells in an acute liver failure model.
AB  - AIM: To investigate a dual labeling technique, which would enable real-time
      monitoring of transplanted embryonic stem cell (ESC) kinetics, as well as long
      term tracking. METHODS: Liver damage was induced in C57/BL6 male mice (n = 40) by
      acetaminophen (APAP) 300 mg/kg administered intraperitoneally. Green fluorescence
      protein (GFP) positive C57/BL6 mouse ESCs were stained with the near-infrared
      fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3
      tetramethylindotricarbocyanine iodide (DiR) immediately before transplantation
      into the spleen. Each of the animals in the cell therapy group (n = 20) received
      5 * 10(6) ESCs 4 h following treatment with APAP. The control group (n = 20)
      received the vehicle only. The distribution and dynamics of the cells were
      monitored in real-time with the IVIS Lumina-2 at 30 min post transplantation,
      then at 3, 12, 24, 48 and 72 h, and after one and 2 wk. Immunohistochemical
      examination of liver tissue was used to identify expression of GFP and albumin.
      Plasma alanine aminotransferase (ALT) was measured as an indication of liver
      damage. RESULTS: DiR-stained ESCs were easily tracked with the IVIS using the
      indocyanine green filter due to its high background passband with minimal
      background autofluorescence. The transplanted cells were confined inside the
      spleen at 30 min post-transplantation, gradually moved into the splenic vein, and
      were detectable in parts of the liver at the 3 h time-point. Within 24 h of
      transplantation, homing of almost 90% of cells was confirmed in the liver. On day
      three, however, the DiR signal started to fade out, and ex vivo IVIS imaging of
      different organs allowed signal detection at time-points when the signal could
      not be detected by in vivo imaging, and confirmed that the highest photon
      emission was in the liver (P < 0.0001). At 2 wk, the DiRsignal was no longer
      detectable in vivo; however, immunohistochemistry analysis of constitutively
      expressed GFP was used to provide an insight into the distribution of the cells.
      GFP +ve cells were detected in tissue sections resembling hepatocytes and were
      dispersed throughout the hepatic parenchyma, with the presence of a larger number
      of GFP +ve cells incorporated within the sinusoidal endothelial lining. Very
      faint albumin expression was detected in the transplanted GFP +ve cells at 72 h;
      however at 2 wk, few cells that were positive for GFP were also strongly positive
      for albumin. There was a significant improvement in serum levels of ALT, albumin
      and bilirubin in both groups at 2 wk when compared with the 72 h time-point. In
      the cell therapy group, serum ALT was significantly (P = 0.016) lower and albumin
      (P = 0.009) was significantly higher when compared with the control group at the
      2 wk time-point; however there was no difference in mortality between the two
      groups. CONCLUSION: Dual labeling is an easy to use and cheap method for
      longitudinal monitoring of distribution, survival and engraftment of transplanted
      cells, and could be used for cell therapy models.

PMID- 22363118
TI  - Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes
      differentially modulate the excitability of murine small intestinal afferents.
AB  - AIM: To assess the role of hyperpolarization-activated cyclic nucleotide-gated
      cation (HCN) channels in regulating the excitability of vagal and spinal gut
      afferents. METHODS: The mechanosensory response of mesenteric afferent activity
      was measured in an ex vivo murine jejunum preparation. HCN channel activity was
      recorded through voltage and current clamp in acutely dissociated dorsal root
      ganglia (DRG) and nodose ganglia (NG) neurons retrogradely labeled from the small
      intestine through injection of a fluorescent marker (DiI). The isoforms of HCN
      channels expressed in DRG and NG neurons were examined by immunohistochemistry.
      RESULTS: Ramp distension of the small intestine evoked biphasic increases in the
      afferent nerve activity, reflecting the activation of low- and high-threshold
      fibers. HCN blocker CsCl (5 mmol/L) preferentially inhibited the responses of low
      threshold fibers to distension and showed no significant effects on the high
      threshold responses. The effect of CsCl was mimicked by the more selective HCN
      blocker ZD7288 (10 MUmol/L). In 71.4% of DiI labeled DRG neurons (n = 20) and
      90.9% of DiI labeled NG neurons (n = 10), an inward current (I(h) current) was
      evoked by hyperpolarization pulses which was fully eliminated by extracellular
      CsCl. In neurons expressing I(h) current, a typical "sag" was observed upon
      injection of hyperpolarizing current pulses in current-clamp recordings. CsCl
      abolished the sag entirely. In some DiI labeled DRG neurons, the I(h) current was
      potentiated by 8-Br-cAMP, which had no effect on the I(h) current of DiI labeled
      NG neurons. Immunohistochemistry revealed differential expression of HCN isoforms
      in vagal and spinal afferents, and HCN(2) and HCN(3) seemed to be the dominant
      isoform in DRG and NG, respectively. CONCLUSION: HCNs differentially regulate the
      excitability of vagal and spinal afferent of murine small intestine.

PMID- 22363119
TI  - Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal
      squamous cell carcinoma.
AB  - AIM: To investigate the expression and methylation status of the secreted
      frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC)
      and explore its role in ESCC carcinogenesis. METHODS: Seven ESCC cell lines (KYSE
      30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human
      esophageal epithelial cell line (Het-1A), 20 ESCC tissue samples and 20 paired
      adjacent non-tumor esophageal epithelial tissues were analyzed in this study.
      Reverse-transcription polymerase chain reaction (RT-PCR) was employed to
      investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and
      paired adjacent normal tissue. Methylation status was evaluated by methylation
      specific PCR and bisulfite sequencing. The correlation between expression and
      promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2'
      deoxycytidine. To assess the potential role of SFRP2 in ESCC, we established
      stable SFRP2-transfected cells and examined them with regard to cell
      proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.
      RESULTS: SFRP2 mRNA was expressed in the immortalized normal esophageal
      epithelial cell line but not in seven ESCC cell lines. By methylation-specific
      PCR, complete methylation was detected in three cell lines with silenced SFRP2
      expression, and extensive methylation was observed in the other four ESCC cell
      lines. 5-aza-2'-deoxycytidine could restore the expression of SFRP2 mRNA in the
      three ESCC cell lines lacking SFRP2 expression. SFRP2 mRNA expression was
      obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 +/-
      0.398 vs 1.51 +/- 0.399, P < 0.01). SFRP2 methylation was higher in tumor tissue
      than in paired normal tissue (95% vs 65%, P < 0.05). The DNA methylation status
      of the SFRP2 correlated inversely with the SFRP2 expression. To assess the
      potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and
      control counterparts by introducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA 
      empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the
      forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the
      control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced
      colony formation in vitro (47.17% +/- 15.61% vs 17% +/- 3.6%, P = 0.031) and
      tumor growth in nude mice (917.86 +/- 249.35 mm(3)vs 337.23 +/- 124.43 mm(3), P <
      0.05). Using flow cytometry analysis, we found a significantly higher number of
      early apoptotic cells in SFRP2-transfected cells than in the control cells (P =
      0.025). The mean cell number in the S and G2-M phases of the cell cycle was also
      significantly lower in SFRP2-transfected KYSE30 cells compared with mock
      transfected counterparts. CONCLUSION: Silencing of SFRP2 expression through
      promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of
      its tumor-suppressive activity.

PMID- 22363120
TI  - Response evaluation of chemotherapy in metastatic colorectal cancer by contrast
      enhanced ultrasound.
AB  - AIM: To evaluate whether contrast enhanced ultrasound (CEUS) might also be used
      for response prediction and early response evaluation in patients receiving
      bevacizumab based chemotherapy for metastasized colorectal cancer. METHODS:
      Thirty consecutive patients with non primary resectable liver metastases from
      colorectal cancer underwent CEUS before treatment (CEUS date 1) and before the
      second (CEUS date 2) and fourth (CEUS date 3) cycle of bevacizumab based
      chemotherapy. Three parameters [PEAK, Time to peak (TTP) and RISE RATE]were
      correlated with radiological response. RESULTS: For neoadjuvant purpose a
      reduction of tumour mass was required to assume clinical response. Based on these
      response criteria there was a significant (P < 0.001) correlation in TTP between
      metastases of responders (9.08 s) and non-responders (14.76 s) archived on CEUS
      date 1. By calculating a standardized quotient (metastases divided by normal
      liver tissue) we were able to define a cut off, predicting response with a
      sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative
      intention only those patients with progressive disease were classified as non
      responders. In this stetting TTP was also significantly (P < 0.01) different
      between responders and non-responders. In contrast, Peak and Rise rate did not
      show any significant difference between responder and non-responder. CONCLUSION:
      CEUS might serve as a surrogate marker to predict treatment response in patients
      with metastasized colorectal cancer who receive antiangiogenic therapy.

PMID- 22363121
TI  - Ambispective comparative study of two surgical strategies for liver hydatidosis.
AB  - AIM: To investigate the morbidity, mortality, recurrence and technical aspects of
      two distinct surgical strategies that were implemented in successive periods.
      METHODS: Ninty-two patients with 113 cysts underwent surgical procedures. The
      study was divided into 2 periods. Data from first period (P1) were compiled
      retrospectively. The surgical strategy was conservative surgery. The second
      period (P2) included a prospective study conducted according to a protocol
      following the criterion that radical procedures should be performed whenever it
      is technically feasible. RESULTS: Patients of both periods showed no
      statistically significant differences in age, gender, cyst location or mortality.
      Among the P2 group, patients exhibited more preoperative jaundice, and cyst size
      was smaller (P < 0.05). Changes in surgical strategy increased the rate of
      radical surgery, decreases morbidity and in-hospital stay (P < 0.001). A negative
      result in P2 was the death of two old patients (4.8%) who had undergone
      conservative treatments. The rate of radical surgery in P2 was around 75%.
      CONCLUSION: Radical surgery should be the technique of choice whenever it is
      feasible, because it diminishes morbidity and in-hospital stay. Conservative
      surgery must be employed only in selected cases.

PMID- 22363122
TI  - Tracheobronchial Polyflex stents for the management of benign refractory
      hypopharyngeal strictures.
AB  - AIM: To describe a modified technique for placement of a tracheobronchial self
      expanding plastic stent (SEPS) in patients with benign refractory hypopharyngeal
      strictures in order to improve dysphagia and allow stricture remodeling. METHODS:
      A case series of four consecutive patients with complex hypopharyngeal strictures
      after combined therapy for laryngeal cancer, previously submitted to multiple
      sessions of dilation without lasting improvement, is presented. All patients
      underwent placement of a small diameter and unflared tracheobronchial SEPS. Main
      outcome measurements were improvement of dysphagia and avoiding of repeated
      dilation. RESULTS: The modified introducer system allowed an easy and technically
      successful deployment of the tracheobronchial Polyflex stent through the
      stricture. All four patients developed complications related to stent placement.
      Two patients had stent migration (one proximal and one distal), two patients
      developed phanryngocutaneous fistulas and all patients with stents in situ for
      more than 8 wk had hyperplastic tissue growth at the upper end of the stent.
      Stricture recurrence was observed at 4 wk follow-up after stent removal in all
      patients. CONCLUSION: Although technically feasible, placement of a
      tracheobronchial SEPS is associated with a high risk of complications. Small
      diameter stents must be kept in place for longer than 3 mo to allow adequate time
      for stricture remodeling.

PMID- 22363123
TI  - Leptin and peroxisome proliferator-activated receptor gamma expression in
      colorectal adenoma.
AB  - AIM: To investigate the expressions of leptin and peroxisome proliferator
      activated receptor gamma (PPARG) in relation to body mass index (BMI). METHODS:
      We evaluated leptin and PPARG expression in 30 adenomas over 1 cm in size by
      immunohistochemical staining. In addition, clinicopathologic features including
      BMI were assessed. RESULTS: PPARG and leptin expression showed a strong positive
      correlation (P = 0.035). The average BMI of the leptin-positive group was higher
      than that of the leptin-negative group (25.4 +/- 3.4 kg/m(2)vs 22.6 +/- 2.4
      kg/m(2), P = 0.018), and leptin expression was significantly correlated with high
      BMI (P = 0.024). Leptin expression was more frequently observed in
      intermediate/high grade dysplasia than in low grade dysplasia (P = 0.030).
      However, PPARG expression was not correlated with BMI and grade of dysplasia.
      CONCLUSION: BMI has influenced on the leptin expression of colorectal adenoma.
      The exact mechanism underlies the strong correlation between leptin and PPARG
      expression needs further study.

PMID- 22363124
TI  - ABO blood type, diabetes and risk of gastrointestinal cancer in northern China.
AB  - AIM: To explore the potential risk factors related to gastrointestinal cancer in
      northern China. METHODS: A total of 3314 cases of gastrointestinal cancer
      (esophageal, gastric, pancreatic and biliary) and 2223 controls (including
      healthy individuals, glioma and thyroid cancer) were analyzed by case-control
      study. Multivariable logistic regression analysis was applied to evaluate the
      association between different cancers and hepatitis B surface antigen, sex, age,
      blood type, diabetes, or family history of cancer. RESULTS: Type 2 diabetes was
      significantly associated with gastric, biliary and pancreatic cancer with an OR
      of 2.0-3.0. Blood type B was significantly associated with esophageal cancer [odd
      ratio (OR) = 1.53, 95% confidence interval (CI) = 1.10-2.14] and biliary cancer
      (OR = 1.49, 95% CI = 1.09-2.05). The prevalence of type 2 diabetes was
      significantly higher in gastric, biliary and pancreatic cancers compared with
      other groups, with ORs ranging between 2.0 and 3.0. Family history of cancer was
      strongly associated with gastrointestinal compared with other cancers.
      CONCLUSION: Blood type B individuals are susceptible to esophageal and biliary
      cancer. Type 2 diabetes is significantly associated with gastric, biliary and
      especially pancreatic cancer.

PMID- 22363125
TI  - Identification of differential gene expressions in colorectal cancer and polyp by
      cDNA microarray.
AB  - AIM: To screen the differential expressed genes in colorectal cancer and polyp
      tissue samples. METHODS: Tissue specimens containing 16 cases of colorectal
      adenocarcinoma and colorectal polyp vs normal mucosae were collected and
      subjected to cDNA microarray and bioinformatical analyses. Quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) was used to confirm some of the
      cDNA microarray data. RESULTS: The experimental data showed that eight genes were
      differentially expressed, most of which were upregulated in adenomatous polyp
      lesions. Forty-six genes expressions were altered in colorectal cancers, of which
      29 were upregulated and 17 downregulated, as compared to the normal mucosae. In
      addition, 18 genes were similarly altered in both adenomatous polyps and
      colorectal cancer. qRT-PCR analyses confirmed the cDNA microarray data for four
      of those 18 genes: MTA1, PDCD4, TSC1 and PDGFRA. CONCLUSION: These differentially
      expressed genes likely represent biomarkers for early detection of colorectal
      cancer and may be potential therapeutic targets after confirmed by further
      studies.

PMID- 22363126
TI  - Study on RIZ1 gene promoter methylation status in human esophageal squamous cell
      carcinoma.
AB  - AIM: To investigate the promoter region methylation status of retinoblastoma
      protein-interacting zinc finger gene 1 (RIZ1) in the human esophageal squamous
      cell carcinoma (ESCC) cell lines and tissues and verify the relationship between
      methylation of RIZ1 and oncogenesis, tumor progression and metastasis etc of
      ESCC. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to
      investigate the promoter region methylation status of RIZ1 in 6 ESCC cell lines.
      One cell line where RIZ1 promoter region methylation was detected was selected
      for the next study, where the cell line was treated with 5-aza-CdR. Real-time
      polymerase chain reaction was used to investigate its influence on the
      transcription of RIZ1. Experiments using frozen pathological specimens from 47
      ESCC patients were performed using the same MSP methodology. RESULTS: Promoter
      methylation of RIZ1 gene was detected in TE13, CaEs17 and EC109 cell lines and
      the cell line TE13 was chosen for further study. The expression of RIZ1 mRNA in
      TE-13 was up-regulated after treatment with 5-aza-CdR. The rate of methylation in
      carcinomas tissues was significantly higher than those in matched neighboring
      normal and distal ending normal tissue, and the deviation of data was
      statistically significant (chi(2) = 24.136, P < 0.01). Analysis of the gender,
      age familial history, tumour deviation, tumour saturation, lymph gland
      displacement and clinical staging of 47 samples from ESCC patients showed that
      the fluctuation of data was not statistically significant. CONCLUSION: Promoter
      methylation may play an important role in the epigenetic silencing of RIZ1 gene
      expression in human ESCC. RIZ1 is considered to be a potential tumor suppressor
      gene and may be a biological parameter for testing early stage human ESCC.

PMID- 22363127
TI  - Pulmonary embolism with acute pancreatitis: a case report and literature review.
AB  - Acute pancreatitis is an inflammatory disease characterized by local tissue
      injury which can trigger a systemic inflammatory response. So vascular
      complications of pancreatitis are a major cause of morbidity and mortality.
      Pulmonary embolism in acute pancreatitis has been reported to be very rare. We
      reported a case of pulmonary embolism with acute pancreatitis. A 38-year-old
      woman broke out upper abdomen pain without definite inducement. She had no nausea
      and vomiting, fever, dyspnea, cough and expectoration, chest pain. The patient
      had been diagnosed with acute pancreatitis in local hospital. The patient was
      treated with antibiotics and proton pump inhibitors, and the abdomen pain was
      alleviated slightly. But the patient came forth cough and expectoration with a
      little blood, progressive dyspnea. A computed tomographic scan of the abdomen
      revealed pancreatitis. Subsequent computer tomography angiography of chest
      revealed pulmonary embolism (both down pulmonary arteries, left pulmonary artery
      and branch of right pulmonary artery). Dyspnea of the patient got well with
      thrombolytic treatment and anticoagulation therapy. Pulmonary embolism is a rare
      but potentially lethal complication of pancreatitis. Familiarity with this
      complication will aid in its early diagnosis, therapy and prevent pulmonary
      embolism, a rare but catastrophic phenomenon.

PMID- 22363128
TI  - Gastrointestinal stromal tumor and mitosis, pay attention.
AB  - The difference between stages I and III of gastric gastrointestinal stromal tumor
      depends principally on the number of mitosis. According with TNM classification,
      the presence in the tumor of high mitotic rate determines the upgrading. Many
      studies exposed different count techniques in evaluating the number of mitosis.
      An international standardized method to assess mitotic rate is needed.

PMID- 22363129
TI  - Herbal medicines for the management of irritable bowel syndrome: a comprehensive
      review.
AB  - Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence.
      Because of various factors involved in its pathophysiology and disappointing
      results from conventional IBS medications, the treatment of IBS is challenging
      and use of complementary and alternative medicines especially herbal therapies is
      increasing. In this paper, electronic databases including PubMed, Scopus, and
      Cochrane library were searched to obtain any in vitro, in vivo or human studies
      evaluating single or compound herbal preparations in the management of IBS. One
      in vitro, 3 in vivo and 23 human studies were included and systematically
      reviewed. The majority of studies are about essential oil of Menta piperita as a
      single preparation and STW 5 as a compound preparation. Some evaluated herbs such
      as Curcuma xanthorriza and Fumaria officinalis did not demonstrate any benefits
      in IBS. However, it seems there are many other herbal preparations such as those
      proposed in traditional medicine of different countries that could be studied and
      investigated for their efficacy in management of IBS.

PMID- 22363130
TI  - Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon.
AB  - Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions are well
      established biological events which have an important role in not just normal
      tissue and organ development, but in the pathogenesis of diseases. Increasing
      evidence has established their presence in the human colon during colorectal
      carcinogenesis and cancer invasion, chronic inflammation-related fibrosis and in
      the course of mucosal healing. A large body of evidence supports the role for
      transforming growth factor-beta and its downstream Smad signaling, the
      phosphatidylinositol 3'-kinase/Akt/mTOR axis, the Ras-mitogen-activated protein
      kinase/Snail/Slug and FOXC2 pathway, and Hedgehog signaling and microRNAs in the
      development of colorectal cancers via epithelial-to-mesenchymal transition. C-met
      and Frizzled-7, among others, seem to be the principle effectors of mesenchymal
      to-epithelial transition, hence have a role not just in mucosal regeneration but
      in the progression of colonic wall fibrosis. Here we discuss a role for these
      pathways in the initiation and development of the transition events. A better
      understanding of their induction and regulation may lead to the identification of
      pathways and factors that could be potent therapeutic targets. The inhibition of
      epithelial-to-mesenchymal transition using mTOR kinase inhibitors targeting the
      ATP binding pocket and which inhibit both mTORC1 and mTORC2, RNA aptamers or
      peptide mimetics, such as a Wnt5A-mimetic, may all be useful in both cancer
      treatment and delaying fibrosis, while the induction of mesenchymal-to-epithelial
      transition in induced pluripotent stem cells may enhance epithelial healing in
      the case of severe mucosal damage. The preliminary results of the current studies
      are promising, but more clinical investigations are needed to develop new and
      safe therapeutic strategies for diseases of the colon.

PMID- 22363131
TI  - Adamantiades-Behcet's disease-complicated gastroenteropathy.
AB  - Adamantiades-Behcet's disease (ABD) is a chronic, relapsing, systemic vasculitis
      of unknown etiology. It is more prevalent in populations along the ancient Silk
      Road from Eastern Asia to the Mediterranean Basin, and most frequently affects
      young adults between the second and fourth decades of life. ABD-complicated
      gastroenteropathy is a significant cause of morbidity and mortality, with
      abdominal pain as the most common symptom. The ileocecal region is affected
      predominantly, with ulcerations that may lead to penetration and/or perforation,
      whereas other parts of the gastrointestinal system including the esophagus and
      stomach can also be affected. Endoscopy is useful to locate the site and extent
      of the lesions, and tissue biopsy is often warranted to examine the
      histopathology that is often suggestive of underlying vasculitis of small
      veins/venules or, alternatively in some cases, nonspecific inflammation. Bowel
      wall thickening is the most common finding on computed tomography scan. Treatment
      is largely empirical since well-controlled studies are difficult to conduct due
      to the heterogeneity of the disease, and the unpredictable course with
      exacerbation and remission. Corticosteroids with or without other
      immunosuppressive drugs, such as cyclophosphamide, azathioprine, sulfasalazine,
      tumor necrosis factor alpha antagonist or thalidomide should be applied before
      surgery, except in emergency.

PMID- 22363132
TI  - Psychosocial determinants of irritable bowel syndrome.
AB  - From a pure motor disorder of the bowel, in the past few years, irritable bowel
      syndrome (IBS) has become a multifactorial disease that implies visceral
      hypersensitivity, alterations at the level of nervous and humoral communications
      between the enteric nervous system and the central nervous system, alteration of
      the gut microflora, an increased intestinal permeability and minimum intestinal
      inflammation. Psychological and social factors can interfere with the
      communication between the central and enteric nervous systems, and there is proof
      that they are involved in the onset of IBS and influence the response to
      treatment and outcome. There is evidence that abuse history and stressful life
      events are involved in the onset of functional gastrointestinal disorders. In
      order to explain clustering of IBS in families, genetic factors and social
      learning mechanisms have been proposed. The psychological features, such as
      anxiety, depression as well as the comorbid psychiatric disorders, health beliefs
      and coping of patients with IBS are discussed in relation to the symptoms and
      outcome.

PMID- 22363133
TI  - Differential effects of energy balance on experimentally-induced colitis.
AB  - AIM: To characterize the influence of diet-induced changes in body fat on colitis
      severity in SMAD3-/- mice. METHODS: SMAD3-/- mice (6-8 wk of age) were randomly
      assigned to receive a calorie restricted (30% of control; CR), control (CON), or
      high fat (HF) diet for 20 wk and were gavaged with sterile broth or with
      Helicobacter hepaticus (H. hepaticus) to induce colitis. Four weeks after
      infection, mice were sacrificed and the cecum and colons were processed for
      histological evaluation. RESULTS: Dietary treatment significantly influenced body
      composition prior to infection (P < 0.05), with CR mice having less (14% +/- 2%)
      and HF-fed mice more body fat (32% +/- 7%) compared to controls (22% +/- 4%).
      Differences in body composition were associated with alterations in plasma levels
      of leptin (HF > CON > CR) and adiponectin (CON > HF >= CR) (P < 0.05). There were
      no significant differences in colitis scores between CON and HF-fed mice 4 wk
      post-infection. Consistent with this, differences in proliferation and
      inflammation markers (COX-2, iNOS), and infiltrating cell types (CD3+ T
      lymphocytes, macrophages) were not observed. Unexpectedly, only 40% of CR mice
      survived infection with H. hepaticus, with mortality observed as early as 1 wk
      following induction of colitis. CONCLUSION: Increased adiposity does not
      influence colitis severity in SMAD3-/- mice. Importantly, caloric restriction
      negatively impacts survival following pathogen challenge, potentially due to an
      impaired immune response.

PMID- 22363134
TI  - Identification of colorectal cancer metastasis markers by an angiogenesis-related
      cytokine-antibody array.
AB  - AIM: To investigate the angiogenesis-related protein expression profile
      characterizing metastatic colorectal cancer (mCRC) with the aim of identifying
      prognostic markers. METHODS: The expression of 44 angiogenesis-secreted factors
      was measured by a novel cytokine antibody array methodology. The study evaluated
      vascular endothelial growth factor (VEGF) and its soluble vascular endothelial
      growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a
      panel of 16 CRC cell lines. mRNA VEGF and VEGF-A isoforms were quantified by
      quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) and
      vascular endothelial growth factor receptor (VEGFR)-2 expression was analyzed by
      flow cytometry. RESULTS: Metastasis-derived CRC cell lines expressed a
      distinctive molecular profile as compared with those isolated from a primary
      tumor site. Metastatic CRC cell lines were characterized by higher expression of
      angiogenin-2 (Ang-2), macrophage chemoattractant proteins-3/4 (MCP-3/4), matrix
      metalloproteinase-1 (MMP-1), and the chemokines interferon gamma inducible T cell
      alpha chemoattractant protein (I-TAC), monocyte chemoattractant protein I-309,
      and interleukins interleukin (IL)-2 and IL-1alpha, as compared to primary tumor
      cell lines. In contrast, primary CRC cell lines expressed higher levels of
      interferon gamma (IFN-gamma), insulin-like growth factor-1 (IGF-1), IL-6, leptin,
      epidermal growth factor (EGF), placental growth factor (PlGF), thrombopoietin,
      transforming growth factor beta1 (TGF-beta1) and VEGF-D, as compared with the
      metastatic cell lines. VEGF expression does not significantly differ according to
      the CRC cellular origin in normoxia. Severe hypoxia induced VEGF expression up
      regulation but contrary to expectations, metastatic CRC cell lines did not
      respond as much as primary cell lines to the hypoxic stimulus. In CRC primary
      derived cell lines, we observed a two-fold increase in VEGF expression between
      normoxia and hypoxia as compared to metastatic cell lines. CRC cell lines express
      a similar pattern of VEGF isoforms (VEGF121, VEGF165 and VEGF189) despite
      variability in VEGF expression, where the major transcript was VEGF121. No
      relevant expression of VEGFR-2 was found in CRC cell lines, as compared to that
      of human umbilical vein endothelial cells and sVEGFR-1 expression did not depend
      on the CRC cellular origin. CONCLUSION: A distinct angiogenesis-related
      expression pattern characterizes metastatic CRC cell lines. Factors other than
      VEGF appear as prognostic markers and intervention targets in the metastatic CRC
      setting.

PMID- 22363136
TI  - (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione protects rats from carbon
      tetrachloride-induced liver injury and fibrogenesis.
AB  - AIM: To evaluate the hepatoprotective roles of (Z)-5-(4
      methoxybenzylidene)thiazolidine-2,4-dione (SKLB010) against carbon tetrachloride
      (CCl4)-induced acute and chronic liver injury and its underlying mechanisms of
      action. METHODS: In the first experiment, rats were weighed and randomly divided
      into 5 groups (five rats in each group) to assess the protective effect of
      SKLB010 on acute liver injury. For induction of acute injury, rats were
      administered a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl4
      dissolved in olive oil (1:1). Group 1 was untreated and served as the control
      group; group 2 received CCl4 for induction of liver injury and served as the
      model group. In groups 3, 4 and 5, rats receiving CCl4 were also treated with
      SKLB010 at doses of 25, 50 and 100 mg/kg, respectively. Blood samples were
      collected at 6, 12 and 24 h after CCl4 intoxication to determine the serum
      activity of alanine amino transferase. Tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) were determined using enzyme-linked immunosorbent
      assay. At 24 h after CCl4 injection, liver fibrogenesis was evaluated by
      hematoxylin-eosin (HE) staining and immunohistochemical analyses. Cytokine
      transcript levels of TNF-alpha, IL-1beta and inducible nitric oxide synthase in
      the liver tissues of rats were measured using a reverse transcriptase reverse
      transcription-polymerase chain reaction technique. In the second experiment, rats
      were randomly divided into 2 groups (15 rats in each group), and liver injury in
      the CCl4-administered groups was induced by a single intraperitoneal injection of
      2 mL/kg of 50% (v/v) CCl4 dissolved in olive oil (1:1). The SKLB010-treated
      groups received oral 100 mg/kg SKLB010 before CCl4 administration. Five rats in
      each group were sacrificed at 2 h, 6 h, 12 h after CCl4 intoxication and small
      fortions of livers were rapidly frozen for extraction of total RNA, hepatic
      proteins and glutathione (GSH) assays. In the hepatic fibrosis model group, rats
      were randomly divided into 2 groups (5 rats each group). Rats were injected
      intraperitoneally with a mixture of CCl4 (1 mL/kg body weight) and olive oil [1:1
      (v/v)] twice a week for 4 wk. In the SKLB010-treated groups, SKLB010 (100 mg/kg)
      was given once daily by oral gavage for 4 wk after CCl4 administration. The rats
      were sacrificed one week after the last injection and the livers from each group
      were harvested and fixed in 10% formalin for HE and immunohistochemical staining.
      RESULTS: In this rat acute liver injury model, oral administration of SKLB010
      blocked liver tissue injury by down-regulating the serum levels of alanine
      aminotransferase, suppressing inflammatory infiltration to liver tissue, and
      improving the histological architecture of liver. SKLB010 inhibited the
      activation of NF-kappaB by suppressing the degradation of IkappaB, and prevented
      the secretion of pro-inflammatory mediators such as tumor necrosis factor-alpha,
      interleukin-1beta, and the reactive free radical, nitric oxide, at the
      transcriptional and translational levels. In this chronic liver fibrosis model,
      treatment with 100 mg/kg per day SKLB010 attenuated the degree of hepatic
      fibrosis and area of collagen, and blocked the accumulation of smooth-muscle
      actin-expressed cells. CONCLUSION: These results suggest that SKLB010 is a potent
      therapeutic agent for the treatment of CCl4-induced hepatic injury.

PMID- 22363135
TI  - Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma
      cells.
AB  - AIM: To observe the synergistic effects of hyperthermia in oxaliplatin-induced
      cytotoxicity in human colon adenocarcinoma Lovo cells. METHODS: The human colon
      adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University. Cells
      were sealed with parafilm and placed in a circulating water bath, and was
      maintained within 0.01  degrees C of the desired temperature (37  degrees C, 39 
      degrees C, 41  degrees C, 43  degrees C and 45  degrees C). Thermal therapy was
      given alone to the negative control group while oxaliplatin was administered to
      the treatment group at doses of 12.5 MUg/mL and 50 MUg/mL. Identification of
      morphological changes, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay, flow cytometry and Western blotting were used to investigate the
      effect of thermochemotherapy on human colon adenocarcinoma Lovo cells, including
      changes in the signal pathway related to apoptosis. RESULTS: A temperature
      dependent inhibition of cell growth was observed after oxaliplatin exposure,
      while a synergistic interaction was detected preferentially with sequential
      combination. Thermochemotherapy changed the morphology of Lovo cells, increased
      the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population
      in the G0/G1 phase (16.7% +/- 4.8 % in phase S plus 3.7% +/- 2.4 % in phase G2/M,
      P < 0.05). Thermochemotherapy increased apoptosis through upregulating p53, Bax
      and downregulating Bcl-2. Protein levels were elevated in p53, Bax/Bcl-2 in
      thermochemotherapy group as compared with the control group (P < 0.05).
      CONCLUSION: Thermochemotherapy may play an important role in apoptosis via the
      activation of p53, Bax and the repression of Bcl-2 in Lovo cells.

PMID- 22363137
TI  - Clinical outcomes of lung metastasectomy in patients with colorectal cancer.
AB  - AIM: To investigate prognostic factors of survival following curative, non
      palliative surgical removal of lung metastases secondary to colorectal cancer
      (CRC). METHODS: Between 1999 and 2009, a radical metastasectomy with curative
      intent was performed on lung metastases in 21 patients with CRC (15 male and 6
      female; mean age: 57.4 +/- 11.8 years; age range: 29-74 years) who had already
      undergone primary tumour resection. RESULTS: The mean number of lung metastases
      ranged from one to five. The mean overall survival was 71 +/- 35 mo (median: 25
      mo). After adjusting for potential confounders, multivariable Cox regression
      analyses predicted only the number of lung metastases (1 vs >= 2; hazard ratio:
      7.60, 95% confidence interval: 1.18-17.2, P = 0.03) as an independent predictor
      of poor survival following lung resection for metastatic CRC. CONCLUSION:
      Resection of lung metastases is a safe and effective treatment in selected CRC
      patients with single lung metastases.

PMID- 22363138
TI  - Outcome of patients who have undergone total enteroscopy for obscure
      gastrointestinal bleeding.
AB  - AIM: To assess the diagnostic success and outcome among patients with obscure
      gastrointestinal bleeding who underwent total enteroscopy with double-balloon
      endoscopy. METHODS: Total enteroscopy was attempted in 156 patients between
      August 2003 and June 2008 at Hiroshima University Hospital and achieved in 75
      (48.1%). It is assessed whether sources of bleeding were identified, treatment
      methods, complications, and 1-year outcomes (including re-bleeding) after
      treatment, and we compared re-bleeding rates among patients. RESULTS: The source
      of small bowel bleeding was identified in 36 (48.0%) of the 75 total enteroscopy
      patients; the source was outside the small bowel in 11 patients (14.7%) and not
      identified in 28 patients (37.3%). Sixty-one of the 75 patients were followed up
      for more than 1 year (27.2 +/- 13.3 mo). Four (6.6%) of these patients showed
      signs of re-bleeding during the first year, but bleeding did not recur after
      treatment. Although statistical significance was not reached, a marked difference
      was found in the re-bleeding rate between patients in whom total enteroscopy
      findings were positive (8.6%, 3/35) and negative (3.8%, 1/26) (3/35 vs 1/26, P =
      0.63). CONCLUSION: A good outcome can be expected for patients who undergo total
      enteroscopy and receive proper treatment for the source of bleeding in the small
      bowel.

PMID- 22363139
TI  - Nutritional risk index as a predictor of postoperative wound complications after
      gastrectomy.
AB  - AIM: To investigate the correlation between the nutritional risk index (NRI) and
      postoperative wound complications. METHODS: From January 2008 through June 2008,
      669 patients who underwent curative gastrectomy for gastric cancer were included
      in a retrospective study. Medical records of consecutive patients were collected
      and analyzed to determine postoperative wound complication rates. The NRI was
      assessed on the fifth postoperative day and other possible risk factors for the
      incidence of wound complications were analyzed to identify the factors affecting
      postoperative wound complications. Patients with other postoperative
      complications were excluded from the study. RESULTS: On the 5th postoperative
      day, the NRI sh-owed a malnutrition rate of 84.6% among postoperative patients.
      However, postoperative wound complications occurred in only 66/669 (9.86%)
      patients. Of the patients with wound complications, 62/66 (94%) belonged to the
      malnourished group (NRI < 97.5), and 4/66 (6%) patients to the non-malnourished
      group (NRI >= 97.5). The only factor correlated with wound complications was the
      NRI on the 5th postoperative day (odds ratio of NRI >= 97.5 vs NRI < 97.5: 0.653;
      95% confidence interval: 0.326-0.974; P = 0.014) according to univariate analysis
      as well as multivariate analysis. CONCLUSION: This study suggests that
      malnutrition immediately after surgery may play a significant role in the
      development of wound complications.

PMID- 22363140
TI  - Glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38
      dependent mitochondrial pathway.
AB  - AIM: To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte
      apoptosis and, furthermore, to determine whether glycyrrhizin (GL), a known HMGB1
      inhibitor, prevents HMGB1-induced hepatocyte apoptosis. METHODS: A human
      hepatocellular carcinoma cell line stably transfected with a bile acid
      transporter (Huh-BAT cells), were used in this study. Apoptosis was quantified
      using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO
      Percentage apoptosis assay, and its signaling cascades were explored by
      immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by
      using selective inhibitors. It is also tried to identify hepatocyte apoptosis
      affected by the HMGB1 inhibitor, GL. RESULTS: HMGB1 increased cellular apoptosis
      in Huh-BAT cells. HMGB1 led to increased cytochrome c release from mitochondria
      into the cytosol, and induced the cleavage of procaspase 3. However, it did not
      affect the activation of caspase 8. HMGB1-induced caspase 3 activation was
      significantly attenuated by the p38 inhibitor SB203580. GL significantly
      attenuated HMGB1-induced hepatocyte apoptosis. GL also prevented HMGB1-induced
      cytochrome c release and p38 activation in Huh-BAT cells. CONCLUSION: The present
      study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38
      dependent mitochondrial pathway. In addition, GL had an anti-apoptotic effect on
      HMGB1-treated hepatocytes.

PMID- 22363141
TI  - Gastric mucosa-associated lymphoid tissue lymphomas and Helicobacter pylori
      infection: a Colombian perspective.
AB  - AIM: To assess the significance of chromosome translocation t(11;18)(q21;q21), B
      cell lymphoma 10 (BCL-10) protein and Helicobacter pylori (H. pylori) infection
      in gastric mucosa-associated lymphoid tissue (MALT) lymphoma in Colombia.
      METHODS: Fifty cases of gastric MALT lymphoma and their respective post-treatment
      follow-up biopsies were examined to assess the presence of the translocation
      t(11;18)(q21;q21) as identified by fluorescence in situ hybridization; to detect
      protein expression patterns of BCL10 using immunohistochemistry; and for
      evaluation of tumor histology to determine the correlation of these factors and
      resistance to H. pylori eradication. RESULTS: Infection with H. pylori was
      confirmed in all cases of gastric MALT lymphoma in association with chronic
      gastritis. Bacterial eradication led to tumor regression in 66% of cases. The
      translocation t(11;18)(q21;q21) was not present in any of these cases, nor was
      there evidence of tumor transformation to diffuse large B-cell lymphoma. Thirty
      four percent of the patients showed resistance to tumor regression, and within
      this group, 7 cases, representing 14% of all those analyzed, were considered to
      be t(11;18)(q21;q21)-positive gastric MALT lymphomas. Protein expression of BCL10
      in the nucleus was associated with the presence of translocation and treatment
      resistance. Cases that were considered unresponsive to therapy were
      histologically characterized by the presence of homogeneous tumor cells and a
      lack of plasmacytic differentiation. Responder cases exhibited higher cellular
      heterogeneity and a greater frequency of plasma cells. CONCLUSION: Both
      t(11;18)(q21;q21)-positive MALT lymphoma cases and those with nuclear BCL10
      expression are considered resistant to H. pylori eradication. It is suggested
      that chronic antigenic stimulation is not a dominant event in resistant cases.

PMID- 22363142
TI  - Clinical impact of multidetector computed tomography before double-balloon
      enteroscopy for obscure gastrointestinal bleeding.
AB  - AIM: To evaluate the clinical impact of multidetector computed tomography (MDCT)
      before double-balloon endoscopy (DBE) for patients with obscure gastrointestinal
      bleeding (OGIB). METHODS: A retrospective analysis of prospectively collected
      cases with DBE and MDCT for overt OGIB was conducted from April 2004 to April
      2010 at Changhua Christian Hospital. We evaluated the clinical impact of MDCT on
      the subsequent DBE examinations and the diagnostic yields of both MDCT and DBE
      respectively. RESULTS: From April 2004 to April 2010, a total of 75 patients
      underwent DBE for overt OGIB. Thirty one cases received MDCT followed by DBE for
      OGIB. The overall diagnostic yields of DBE and MDCT was 93.5% and 45.2%. The MDCT
      had a high diagnostic yield of tumor vs non-tumor etiology of OGIB (85.7% vs
      33.3%, P = 0.014). Additionally, the choice of initial route of DBE was correct
      in those with a positive MDCT vs negative MDCT (100% vs 52.9%, P = 0.003).
      CONCLUSION: This study suggests MDCT as a triage tool may identify patients who
      will benefit from DBE and aid the endoscopist in choosing the most efficient
      route.

PMID- 22363143
TI  - Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor
      patients.
AB  - AIM: To investigate the efficacy and safety of imatinib dose escalation in
      Chinese patients with advanced gastrointestinal stromal tumor (GIST). METHODS:
      Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled
      in this study. Patients received imatinib with dose escalation to 600 mg/d, and
      further dose escalation to 800 mg/d if imatinib 600 mg/d failed. Progression-free
      survival, overall survival, clinical efficacy, c-kit/PDGFRA genotype and safety
      were evaluated. RESULTS: 52 patients were enrolled in this study. For the 47
      evaluable patients receiving imatinib (600 mg/d), the disease control rate was
      40.4%, and the median progression-free survival for all patients was 17 wk (95%
      CI: 3.9-30.1). The median overall survival after dose escalation was 81 wk (95%
      CI: 36.2-125.8). Adverse events, mainly edema, fatigue, granulocytopenia and skin
      rash were tolerable. However, further dose escalation (800 mg/d) in 14 cases was
      ineffective, with disease progression and severe adverse events. Among 30 cases
      examined for gene mutations, patients with exon 9 mutations experienced a better
      progression-free survival of 47 wk. CONCLUSION: Imatinib dose escalation to 600
      mg/d is more appropriate for Chinese patients and may achieve further survival
      benefit.

PMID- 22363144
TI  - Apoptosis of human cholangiocarcinoma cells induced by ESC-3 from Crocodylus
      siamensis bile.
AB  - AIM: To investigate the effects of ESC-3 isolated from crocodile bile on the
      growth and apoptosis induction of human cholangiocarcinoma cells. METHODS: ESC-3
      was isolated from crocodile bile by Sephadex LH-20 and RP-18 reversed-phase
      column. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was
      conducted to determine the effects of ESC-3 on the proliferation of human
      cholangiocarcinoma cell lines (QBC939, Sk-ChA-1 and MZ-ChA-1). Giemsa staining,
      Hoechst 33258 and acridine orange/ethidium bromide staining showed the
      morphological changes of Mz-ChA-1 cells exposed to ESC-3 at different
      concentrations. Flow cytometry with regular propidium iodide (PI) staining was
      performed to analyze the cell cycle distribution of Mz-ChA-1 cells and to assess
      apoptosis by annexin v-fluorescein isothiocyanate (V-FITC)/PI staining. Rh123
      staining was used to detect the alteration of mitochondrial membrane potential
      (DeltaPsim). The protein levels of Bax, Bcl-2, Cdk2, cytochrome c and caspase-3
      were further confirmed by Western blotting. RESULTS: ESC-3 significantly
      inhibited the growth of three human cholangiocarcinoma cell lines and arrested Mz
      ChA-1 cell cycle at G0/G1 phase. Mz-ChA-1 cells showed typical apoptotic
      morphological changes after treated with ESC-3 (10 MUg/mL) for 48 h. Cell death
      assay indicated that Mz-ChA-1 cells underwent apoptosis in a dose-dependent
      manner induced by ESC-3. In addition, ESC-3 treatment could downregulate the
      protein level of Bcl-2 and upregulate the Bax, leading to the increase in the
      ratio of Bax to Bcl-2 in Mz-ChA-1 cells. Meanwhile, cytochrome c was released
      from the mitochondria into the cytosol, which subsequently initiated the
      activation of caspase-3. All these events were associated with the collapse of
      the mitochondrial membrane potential. CONCLUSION: ESC-3, the active ingredient of
      crocodile bile, induced apoptosis in Mz-ChA-1 cells through the mitochondria
      dependent pathway and may be a potential chemotherapeutic drug for the treatment
      of cholangiocarcinoma.

PMID- 22363145
TI  - Expression of OCT4 in human esophageal squamous cell carcinoma is significantly
      associated with poorer prognosis.
AB  - AIM: To explore the expression pattern of OCT4 in human esophageal squamous cell
      carcinoma and its significance in diagnosis and prognosis. METHODS: Using real
      time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and
      immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer
      cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was
      investigated in a series of 153 esophageal squamous cell carcinoma samples using
      immunohistochemistry and explored its association with clinicopathological
      features. RESULTS: Immunohistochemically, OCT4 positive immunostaining was
      observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal
      squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or
      weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27
      (17.6%) were strongly positive. Higher expression level of OCT4 was significantly
      associated with higher histological grade (P < 0.001) and poor clinic outcome (P
      < 0.001). CONCLUSION: The expression of OCT4 enables the tumor to have a higher
      degree of stemness, which in turn results in a poorer clinical outcome for
      patients with esophageal squamous cell carcinoma.

PMID- 22363146
TI  - Pancreatic tuberculosis with acquired immunodeficiency syndrome: a case report
      and systematic review.
AB  - Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic
      carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or
      pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who
      exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient
      was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was
      treated with antituberculous drugs and percutaneous catheter drainage without a
      laparotomy. The clinical presentation, radiographic investigation and management
      of pancreatic TB are summarized in this paper to emphasize the importance of
      considering this rare disease in the differential diagnosis of pancreatic masses
      concomitant with human immunodeficiency virus infection. I also emphasize the
      need for both histopathological and microbiological diagnosis via fine-needle
      aspiration.

PMID- 22363147
TI  - Topical hypopigmenting agents for pigmentary disorders and their mechanisms of
      action.
AB  - Melanin is produced in melanocytes and stored in melanosomes. In spite of its
      beneficial sun-protective effect, abnormal accumulation of melanin results in
      esthetic problems. Hydroquinone, competing with tyrosine, is a major ingredient
      in topical pharmacological agents. However, frequent adverse reactions are
      amongst its major limitation. To solve this problem, several alternatives such as
      arbutin, kojic acid, aloesin, and 4-n-butyl resorcinol have been developed.
      Herein, we classify hypopigmenting agents according to their mechanism of action;
      a) regulation of enzyme, which is subdivided into three categories, i) regulation
      of transcription and maturation of tyrosinase, ii) inhibition of tyrosinase
      activity, and iii) post-transcriptional control of tyrosinase; b) inhibition of
      melanosome transfer, and c) additional mechanisms such as regulation of the
      melanocyte environment and antioxidant agents.

PMID- 22363148
TI  - Utility of Dermoscopy before and after Laser Irradiation in Port Wine Stains.
AB  - BACKGROUND: Port wine stains (PWSs) are commonly treated with pulsed dye laser
      (PDL) as a standard therapy. However, it is not easy to predict the minimal
      effective dose in the first treatment session. OBJECTIVE: The aim of this study
      was to assess whether dermoscopic findings before and after laser irradiation
      corresponded with the clinical improvement of PWS in patients undergoing PDL
      therapy. METHODS: Seven untreated PWSs in 6 patients (a male and 5 females), who
      presented to our hospital between May 2008 to January 2010, were assessed in this
      study. The mean age was 36.3 years, ranging from 14 to 57 years. A PDL with a
      wavelength of 585 nm and a spot size of 7 mm was used. Before and after test
      irradiation, patients underwent dermoscopy and clinical photography, and we
      assessed whether the dermoscopic findings corresponded with clinical improvement
      after 3 months. RESULTS: There were no obvious differences observed in the
      clinical photographs between each test level immediately after irradiation.
      However, dermoscopic photographs showed differences as the irradiated energy
      increased. These changes corresponded to the clinical improvement after 3 months.
      CONCLUSION: Our study indicates that the minimal effective fluence can be
      predicted by observing dermoscopic change immediately after irradiation. We think
      that examining the dermoscopic findings immediately after irradiation allows the
      laser surgeon to predict the minimal effective fluence and this prevents adverse
      effects of the skin.

PMID- 22363149
TI  - Analysis of cardiovascular risk factors and metabolic syndrome in korean patients
      with psoriasis.
AB  - BACKGROUND: In previous studies, psoriasis has been reported to be associated
      with metabolic syndrome. OBJECTIVE: The purpose of this study was to evaluate
      risk factors for metabolic syndrome in psoriasis patients and to compare the
      prevalence of metabolic syndrome in psoriasis and control groups. METHODS: All
      patients (n=490) and controls (n=682) were investigated for cardiovascular risk
      factors, including central obesity, hypertension, fasting plasma glucose levels,
      and blood levels of triglycerides and high-density lipoprotein (HDL). RESULTS: We
      found no statistical association between psoriasis and the prevalence of
      metabolic syndrome when controlling for age and gender. Among individual
      components of metabolic syndrome, only increased triglyceride levels was
      significantly prevalent in patients psoriasis. The incidence of other factors
      such as central obesity, hypertension, fasting plasma glucose and HDL in the
      psoriasis group were similar to or lower than those in the control group.
      Although psoriasis patients with metabolic syndrome had severe and large plaque
      type psoriasis, the association of metabolic syndrome with the severity or
      clinical subtype of psoriasis was not significant after adjusting for age and
      gender. CONCLUSION: Our results suggest that there is no close correlation
      between psoriasis and metabolic syndrome in Korean patients.

PMID- 22363150
TI  - Cedrol Enhances Extracellular Matrix Production in Dermal Fibroblasts in a MAPK
      Dependent Manner.
AB  - BACKGROUND: The extracellular matrix (ECM) produced by dermal fibroblasts
      supports skin structure, and degradation and/or reduced production of ECM are the
      main causes of wrinkle formation. OBJECTIVE: The aim of this study was to
      identify the active ingredient that enhances ECM production in dermal
      fibroblasts. METHODS: Polarity-based fractionation was used to isolate the active
      ingredient from natural extracts, and the effects of cedrol (isolated from
      Pterocarpus indicusirginia) on ECM production in cultured human dermal
      fibroblasts was investigated by reverse transcription-polymerase chain reaction,
      enzyme linked immunosorbent assay, and Western blot analysis. RESULTS: Cedrol
      accelerated fibroblast growth in a dose-dependent manner and increased the
      production of type 1 collagen and elastin. Phosphorylation of p42/44
      extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and
      Akt was markedly increased by cedrol, indicating that enhanced ECM production is
      linked to activation of intracellular signaling cascades. CONCLUSION: These
      results indicate that cedrol stimulates ECM production, with possible
      applications to the maintenance of skin texture.

PMID- 22363151
TI  - A clinical study of cutaneous adverse reactions to nonionic contrast media in
      Korea.
AB  - BACKGROUND: The use of intravenous contrast media (CM) has increased for the
      diagnosis of several diseases. The newly developed low osmolar nonionic contrast
      agents cause significantly decreased adverse reactions than the higher osmolar
      ones. However, adverse reactions may still occur, ranging in severity from minor
      side effects to severe complications. However, there have been few reports about
      cutaneous adverse reactions (CARs) to nonionic monomer CM. OBJECTIVE: The purpose
      of this study was to evaluate clinical features of CAR to intravenous nonionic
      monomer CM. METHODS: A total 47,338 examinees underwent intravenous iodinated
      contrast-enhanced computed tomography scan using nonionic monomer CM. Among the
      adverse reactions to the CM, we divided them into cutaneous or noncutaneous and
      immediate (<1 hr) or late (>=1 hr) adverse reactions. RESULTS: Adverse reactions
      were noted in 62 cases out of the total 47,338 cases; 50 cases (80.7%) were
      categorized CARs. Among them, there were 24 male and 26 female patients. There
      was no significant difference between the sexes, and CARs occurred in all age
      groups. The highest occurrence was in the age range of 50~59 years. CARs included
      urticaria (78%), angioedema (10%), maculopapular rash (8%), erythema (2%), and
      pruritus without rash (2%). Immediate reactions were 92% (46 cases), while late
      reactions were 8% (4 cases). CONCLUSION: CARs to nonionic monomer CM accounted
      for most of the adverse reactions (80.7%) and urticaria was the most common.

PMID- 22363152
TI  - Effect of IGF-I on Hair Growth Is Related to the Anti-Apoptotic Effect of IGF-I
      and Up-Regulation of PDGF-A and PDGF-B.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) shares a high degree of
      structural and functional homology with insulin and is a potent mitogen
      supporting cell growth and survival in many kinds of the tissues and cells. It
      also plays a role in some differentiation and anti-apoptotic functions. In
      previous reports, it has been shown that IGF-I stimulates hair follicle (HF)
      growth, maintains the anagen stage, and postpones the catagen stage. OBJECTIVE:
      The exact mechanism of the effect of IGF-I on HF growth is not yet established.
      Therefore, we investigated the relationships between IGF-I and various other
      factors (i.e. apoptosis related molecules, pro-inflammatory cytokines, other
      growth factors, etc.) in the control of HF growth. METHODS: The effect of IGF-I
      on human hair growth was measured using an organ culture model of human HFs and
      compared with a control group that did not receive IGF-I. We also measured mRNA
      expression of factors related to hair growth and apoptosis (which was determined
      by reverse transcription polymerase chain reaction (RT-PCR). RT-PCR was done on
      days 2, 4, 6, and 8 of organ culture. RESULTS: In organ cultured human hair
      follicles, IGF-I had a positive effect on the rate of linear hair growth. IGF-I
      maintained the anagen phase. IGF-I increased the expression of platelet-derived
      growth factor (PDGF)-A, PDGF-B and the expression ratio of Bcl-2/Bax. CONCLUSION:
      The effect of IGF-I on hair growth appears to be related to the upregulation of
      PDGF-A and PDGF-B and to the anti-apoptotic effect of IGF-I.

PMID- 22363153
TI  - The Prevalence, Genotype and Antimicrobial Susceptibility of High- and Low-Level
      Mupirocin Resistant Methicillin-Resistant Staphylococcus aureus.
AB  - BACKGROUND: Mupirocin has been used for the treatment of skin infections and
      eradication of nasal carriage of methicillin-resistant Staphylococcus aureus
      (MRSA). The increased use of this antibiotic has been accompanied by outbreaks of
      MRSA that are resistant to mupirocin. OBJECTIVE: This study aims to determine the
      prevalence, genotype and antimicrobial susceptibility of mupirocin-resistant MRSA
      from 4 Korean hospitals. METHODS: A total 193 MRSA clinical isolates were
      collected from four university hospitals. Antimicrobial susceptibility tests,
      including mupirocin, and pulsed-field gel electrophoresis (PFGE) pattern analysis
      were performed. RESULTS: Overall, 27 of the 193 (14.1%) MRSA isolates were
      resistant to mupirocin. All of the (A) hospital isolates showed high-level (HL)
      mupirocin resistance and the low-level (LL) mupirocin resistant strains were from
      three other hospitals. The PFGE patterns of 16 mupirocin-resistant isolates were
      divided into 5 clusters (1-5), and the nine HL mupirocin-resistant isolates
      belonged to cluster 1. Both the HL and LL mupirocin-resistant MRSA isolates were
      susceptible to vancomycin and rifampin, but they were resistant to ciprofloxacin,
      clindamycin and tetracycline. The erythromycin and fusidic acid resistance rates
      were different between the HL and LL resistant isolates. CONCLUSION: HL mupirocin
      resistant isolates that could transfer this resistance to other bacteria were
      detected and these isolates were clonally related. The emergence of mupirocin
      resistant isolates emphasizes the importance of using antibiotics judiciously and
      carefully monitoring the prevalence of mupirocin resistance.

PMID- 22363154
TI  - Inhibitory Effect of Vitamin U (S-Methylmethionine Sulfonium Chloride) on
      Differentiation in 3T3-L1 Pre-adipocyte Cell Lines.
AB  - BACKGROUND: S-methylmethionine sulfonium chloride was originally called vitamin U
      because of its inhibition of ulceration in the digestive system. Vitamin U is
      ubiquitously expressed in the tissues of flowering plants, and while there have
      been reports on its hypolipidemic effect, its precise function remains unknown.
      OBJECTIVE: This study was designed to evaluate the anti-obesity effect of vitamin
      U in 3T3-L1 pre-adipocyte cell lines. METHODS: We cultured the pre-adipocyte cell
      line 3T3L1 to overconfluency and then added fat differentiation-inducing media
      (dexamethasone, IBMX [isobutylmethylxanthine], insulin, indomethacin) and
      different concentrations (10, 50, 70, 90, 100 mM) of vitamin U. Then, we
      evaluated changes in the levels of triglycerides (TGs), glycerol-3-phosphate
      dehydrogenase (G3PDH), AMP-activated protein kinase (AMPK), adipocyte-specific
      markers (peroxisome proliferator-activated receptor gamma [PPAR-gamma],
      CCAAT/enhancer-binding protein alpha [C/EBP-alpha], adipocyte differentiation and
      determination factor 1 [ADD-1], adipsin, fatty acid synthase, lipoprotein lipase)
      and apoptosis-related signals (Bcl-2, Bax). RESULTS: There was a gradual decrease
      in the level of TGs, C/EBP-alpha, PPAR-gamma, adipsin, ADD-1 and GPDH activity
      with increasing concentrations of vitamin U. In contrast, we observed a
      significant increase in AMPK activity with increasing levels of vitamin U. The
      decrease in bcl-2 and increase in Bax observed with increasing concentrations of
      vitamin U in the media were not statistically significant. CONCLUSION: This study
      suggests that vitamin U inhibits adipocyte differentiation via down-regulation of
      adipogenic factors and up-regulation of AMPK activity.

PMID- 22363155
TI  - Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230
      for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease
      associated with autoantibodies against BP180 and BP230. Enzyme-linked
      immunosorbent assay (ELISA) is a sensitive tool for the detection of
      immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. OBJECTIVE: The
      aim of this study was to evaluate the usefulness of ELISA for diagnosing and
      monitoring the disease activity of BP. METHODS: We evaluated serum IgG levels of
      anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis
      bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through
      retrospective review of the medical records, the clinical characteristics of BP
      including disease activity, duration, pruritus severity and peripheral blood
      eosinophil counts were assessed. RESULTS: The sensitivity of BP180 ELISA was
      97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity
      of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was
      90.3%. BP180 ELISA scores showed strong associations with disease activity,
      pruritus severity, peripheral blood eosinophil counts, and disease duration,
      whereas BP230 ELISA scores did not. CONCLUSION: BP180 and BP230 ELISAs are highly
      sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a
      sensitive tool for monitoring the disease activity of BP.

PMID- 22363156
TI  - The effect of photodynamic therapy using indole-3-acetic Acid and green light on
      acne vulgaris.
AB  - BACKGROUND: Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA)
      has increasingly been used for the treatment of acne vulgaris and several studies
      have shown its clinical efficacy. However, ALA-PDT needs a relatively long
      incubation period and is frequently associated with adverse effects. Indole-3
      acetic acid (IAA) has been introduced as a new photosensitizer for the treatment
      of acne in recent study. IAA-PDT requires only a short incubation period and the
      procedure is relatively painless in contrast to ALA-PDT. OBJECTIVE: To
      investigate the efficacy and safety of IAA- PDT in the treatment of acne.
      METHODS: Twenty-five patients with facial acne lesions were enrolled in this
      study. IAA-PDT was performed for five sessions at 1-week intervals (week 0~4).
      IAA was treated with 15 minute occlusion, and green light was given for 15
      minutes. Clinical efficacy was determined by evaluating acne lesion counts,
      severity grading, and the Dermatology Life Quality Index (DLQI) at week 0, 2, 4,
      and 5. Sebum secretion and erythema index was measured by Sebumeter and
      Mexameter, respectively, at baseline and one week after each treatment session
      (week 1~5). Histopathological examination was performed at baseline and week 5.
      Adverse effects were recorded throughout the study. RESULTS: All the patients
      completed the study. Numbers of both inflammatory and non-inflammatory acne
      lesions were significantly decreased. Acne severity grade and the DLQI showed
      significant reduction. Sebum secretion and erythema were also reduced.
      Histopathological examination showed a reduction in inflammatory reactions. No
      adverse effects were observed except for transient pruritus in one patient.
      CONCLUSION: PDT using IAA and green light was an effective, simple and safe
      treatment for acne.

PMID- 22363157
TI  - Association between IL17A/IL17RA Gene Polymorphisms and Susceptibility to
      Alopecia Areata in the Korean Population.
AB  - BACKGROUND: Alopecia areata is marked by autoimmune assault on the hair follicle
      resulting in hair loss. T helper 17 cell subset has important roles in protecting
      the host against extracellular pathogens, however, also promotes inflammatory
      pathology in autoimmune disease, and it expresses both interleukin (IL)-17A and
      IL-17F, which can signal via the IL-17 receptor A. OBJECTIVE: To investigate the
      significance of IL17A and IL17RA gene polymorphisms in the susceptibility to
      alopecia areata. METHODS: We conducted case-control association study of 238
      alopecia areata patients and 270 matched healthy controls. Allele frequency of
      total 2 single nucleotide polymorphims in the IL17A gene and 4 single nucleotide
      polymorphims in the IL17RA gene were studied. The statistical analyses were
      performed according to onset age, the presence of familyhistory, clinical
      subtypes, and presence of nail involvement or body hair involvement. RESULTS: One
      single nucleotide polymorphim (rs879577) of IL17RA gene showed significant
      difference between alopecia areata patients group and controls group (p= 0.0288).
      One single nucleotide polymorphim (rs4819554) of IL17RA gene showed significant
      difference between the early onset and late onset alopecia areata (p=0.0421).
      CONCLUSION: IL17RA gene polymorphism might contribute to the increased
      susceptibility to alopecia areata in Korean population, and IL17RA gene
      polymorphism may be associated with onset age.

PMID- 22363158
TI  - Intravenous immunoglobulin treatment in a child with resistant atopic dermatitis.
AB  - In a subgroup of patients suffering from atopic dermatitis (AD), treatment is
      quite difficult even after taking oral immunosuppressants. High-dose intravenous
      immunoglobulin (IVIG) treatment has been reported to be beneficial for them in a
      few uncontrolled trials. Herein we report a case of intractable AD in a 5-year
      old girl who had significant clinical improvement after receiving 3 cycles of
      IVIG treatment (2 g/kg) without notable side effects. Since the first infusion of
      IVIG, the patient's skin lesions improved steadily and the improvement persisted
      until the 8-month follow-up. The eczema area and severity index score decreased
      remarkably, while immunologic parameters did not correlate with clinical
      improvement. This case suggests that IVIG therapy can be quite effective and safe
      for children with resistant AD.

PMID- 22363159
TI  - Delayed diagnosis of scrofuloderma misdiagnosed as a bacterial abscess.
AB  - An 82-year-old woman presented with a four-month history of an ulcerative plaque
      overlying her left neck. This lesion had developed as a subcutaneous nodule,
      gradually increased in size, and evolved into ulcers. Before visiting our
      Dermatology clinic, the patient had been diagnosed as having a bacterial abscess,
      but treatments with antibiotics were unsuccessful. The presence of a purulent
      discharge and prominent ulceration caused further confusion as bacterial abscess,
      and radiologic evaluation on computed tomography also led to the possibilities of
      secondary lesions from an abscess or malignancy. However, the characteristic
      appearance of her lesion allowed us to discern cutaneous tuberculosis, especially
      scrofuloderma. Based on clinical examinations, staining for acid-fast bacilli,
      and positive findings of polymerase chain reaction, a quick diagnosis of
      scrofuloderma was made. After that, she was treated successfully with anti
      tuberculosis therapy and the ulcer healed. Our case highlights the problem of
      delayed diagnosis of scrofuloderma presenting as a bacterial abscess. In
      conclusion, having a high index of suspicion is needed to diagnose cutaneous
      tuberculosis correctly.

PMID- 22363160
TI  - Cutaneous sarcoidosis clinically mimicking necrobiosis lipoidica in a patient
      with systemic sarcoidosis.
AB  - A 70-year-old woman with an 8-year history of systemic sarcoidosis developed
      round, red-brown eruptions, with central atrophic lesions on her lower legs. The
      features of the biopsy specimen resembled those of necrobiosis lipoidica (NL),
      but although necrobiosis was present there were well-formed non-necrotizing
      granulomas in the dermis. The histological diagnosis was cutaneous sarcoidosis.
      Systemic sarcoidosis presenting with NL has rarely been reported. The
      histological features of cutaneous sarcoidosis sometimes mimic those of other
      granulomatous diseases, including NL and granuloma annulare, which are difficult
      to distinguish. We discuss the novel association between sarcoidosis and other
      granulomatous diseases.

PMID- 22363161
TI  - Merkel Cell Carcinoma Concurrent with Bowen's Disease.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the
      elderly and immunocompromised patients. It is occasionally found coexisting with
      other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic
      keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old
      woman presented with a 6-month history of an irregularly shaped erythematous
      patch on the left mandibular angle. Three months later, a 1.5*1.0 cm sized
      painless and rapidly growing erythematous nodule developed on the patch.
      Microscopically, the patch lesion was consistent with that of Bowen disease. The
      nodular lesion showed a number of small uniform hyperchromatic cells with scanty
      cytoplasm. It showed dense small-cell like nodular infiltration in the dermis.
      Immunohistochemical staining for cytokeratin 20 showed a positive result with a
      dot-like perinuclear pattern. Additionally, the result for thyroid transcription
      factor-1 was negative, which is positive in small cell neuroendocrine carcinoma.
      From these findings, we diagnosed this lesion as MCC concurrent with Bowen
      disease.

PMID- 22363162
TI  - Could a growth spurt cause linear focal elastosis like striae distensae?
AB  - Linear focal elastosis (LFE) is characterized by several asymptomatic, yellow,
      palpable, irregularly indurated, striae-like lines extending horizontally across
      the middle and lower back. A focal increase in elastic fibers is a hallmark of
      the disease as seen from biopsy specimens. The pathogenesis of LFE is unclear, as
      is the association between LFE and striae distensae (SD). However, the prevailing
      opinion is that LFE represents an excessive regenerative process of elastic
      fibers and is analogous to keloidal repair of SD. Although the timing of onset of
      LFE and SD was not synchronous in our patient, the triggering factor was the
      same, which was the growth spurt. This case is supporting the putative
      association between LFE and SD.

PMID- 22363163
TI  - An acquired anemic patch developed after a cyst excision: is it a variant of
      nevus anemicus?
AB  - A 53-year-old male presented with a 6-year duration of a child's-palm sized
      hypopigmented patch located on his neck. He had a history of surgical excision of
      an epidermal cyst on the neck, and the hypopigmented patch developed about one
      month after the excision next to the surgery site. Application of cold or heat
      did not make the lesion distinct from the surrounding skin. Pressure on the
      lesion by a glass slide made the lesion indistinguishable from surrounding
      uninvolved lesions. Giving friction to the lesion failed to induce erythematous
      change, making it clearly visible. Histologically, the lesion showed normal
      findings with adequate numbers of melanocytes in the basal layer. Herein, we
      present an interesting case of an acquired anemic patch which developed after a
      cyst excision. We postulate that nerve damage after surgery that regulates the
      vascular tone of cutaneous vessels may have been an inducing event of the anemic
      patch in this patient.

PMID- 22363164
TI  - Lichen striatus occurring after allogenic peripheral blood stem cell
      transplantation in an adult with aplastic anemia.
AB  - Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that
      follows the lines of Blaschko. The etiology of the eruption is unknown, but
      several theories have been proposed with focus on environmental factors, viral
      infection, cutaneous injury, hypersensitivity, and genetic predisposition. We
      describe a 19-year-old woman who developed a unilateral linear eruption 17 months
      after allogenic peripheral blood stem cell transplantation. Histopathology
      revealed features, which were consistent with LS. To the best of our knowledge,
      our patient is the first case describing the appearance of LS occurring after
      allogenic stem cell transplantation. We speculate that this condition represents
      an unusual form of localized, chronic graft-versus-host disease.

PMID- 22363165
TI  - A simple assay method for melanosome transfer.
AB  - Pigmentation is induced by production of melanin in specialized organelles termed
      melanosomes and by transfer of these organelles from melanocytes to surrounding
      keratinocytes. The chemical basis of melanogenesis is relatively well known but
      the mechanism of melanosome transfer is not well studied. Various pigmentary
      disorders and cosmetic applications require the use of depigmenting agents.
      Currently available topical agents used for the reduction of pigmentation mainly
      include tyrosinase inhibitors and/or melanocyte-cytotoxic agents. Recently,
      several agents have been introduced to inhibit melanosome transfer from
      melanocytes to keratinocytes. However, an experimental model for melanosome
      transfer is not well established. In this study, a simple assay method using flow
      cytometry is described.

PMID- 22363166
TI  - Effects of murine dermal cells on the regulation of hair growth is dependent on
      the cell number and post-natal age of newborn mice.
AB  - Dermal cells from neonatal mice can initiate the formation of hair follicles
      (HFs) when combined with adult mouse epidermal cells and transplanted
      subcutaneously into athymic mice. In the present study, the effects of dermal
      cells on HF formation were tested in terms of total cell number and the time
      course of cell harvest. Results demonstrated that the number of dermal cells is
      critical to the formation of HF. Furthermore, hair forming ability is rapidly
      decreasing as the neonatal mice age. To examine potential differences in gene
      expression, cDNA array was performed. Results demonstrate that numerous molecules
      which are directly involved in receptor and signaling correlated with decreased
      hair inductivity in early time points after delivery. It is reported that bone
      morphogenic protein (BMP)-6 and Wnt3a treatment increased hair inductivity of
      dermal papilla cells. But in our study, no changes were observed in the
      expression levels of BMP-6 and Wnt3a. However, several Wnt related genes
      demonstrate increased or decreased expression levels. Thus, our results suggest
      that co-ordinated regulation of these molecules will be important in hair
      neogenesis within our model system.

PMID- 22363167
TI  - Eczema Confined to Becker's Nevus on the Face: The Behavior of Melanocytes during
      Inflammation.

PMID- 22363168
TI  - Solitary neurofibromas: does an uncommon site exist?

PMID- 22363169
TI  - Clinicopathologic Manifestations of Patients with Fordyce's Spots.

PMID- 22363170
TI  - Acute vesico-bullous eruption from methotrexate overdose in a psoriasis patient.

PMID- 22363171
TI  - Is spontaneous disappearance of nevus depigmentosus possible?

PMID- 22363172
TI  - Numerous mucin nodules in a patient with seropositive wide spread discoid lupus
      erythematosus.

PMID- 22363175
TI  - American college of physicians, internal medicine conference 2010.

PMID- 22363173
TI  - Role of nitrative and oxidative DNA damage in inflammation-related
      carcinogenesis.
AB  - Chronic inflammation induced by biological, chemical, and physical factors has
      been found to be associated with the increased risk of cancer in various organs.
      We revealed that infectious agents including liver fluke, Helicobacter pylori,
      and human papilloma virus and noninfectious agents such as asbestos fiber induced
      iNOS-dependent formation of 8-nitroguanine and 8-oxo-7, 8-dihydro-2'
      deoxyguanosine (8-oxodG) in cancer tissues and precancerous regions. Our results
      with the colocalization of phosphorylated ATM and gamma-H2AX with 8-oxodG and 8
      nitroguanine in inflammation-related cancer tissues suggest that DNA base damage
      leads to double-stranded breaks. It is interesting from the aspect of genetic
      instability. We also demonstrated IL-6-modulated iNOS expression via STAT3 and
      EGFR in Epstein-Barr-virus-associated nasopharyngeal carcinoma and found promoter
      hypermethylation in several tumor suppressor genes. Such epigenetic alteration
      may occur by controlling the DNA methylation through IL-6-mediated JAK/STAT3
      pathways. Collectively, 8-nitroguanine would be a useful biomarker for predicting
      the risk of inflammation-related cancers.

PMID- 22363174
TI  - Good oral health and diet.
AB  - An unhealthy diet has been implicated as risk factors for several chronic
      diseases that are known to be associated with oral diseases. Studies
      investigating the relationship between oral diseases and diet are limited.
      Therefore, this study was conducted to describe the relationship between healthy
      eating habits and oral health status. The dentistry has an important role in the
      diagnosis of oral diseases correlated with diet. Consistent nutrition guidelines
      are essential to improve health. A poor diet was significantly associated with
      increased odds of oral disease. Dietary advice for the prevention of oral
      diseases has to be a part of routine patient education practices. Inconsistencies
      in dietary advice may be linked to inadequate training of professionals.
      Literature suggests that the nutrition training of dentists and oral health
      training of dietitians and nutritionists is limited.

PMID- 22363176
TI  - Reperfusion for STEMI in current Canadian practice: Are we closing the care gap?

PMID- 22363177
TI  - Tracheal agenesis: A rare but fatal congenital anomaly.
AB  - In this report we describe a newborn with a rare case of Type II tracheal
      agenesis and bronchoesophageal fistula. Polyhydramnios and suspected esophageal
      atresia were identified during routine pre-natal ultrasound screening. Upon
      delivery, rigid bronchoscopy, esophagoscopy, and intraoperative fluoroscopy were
      performed, where both bronchi and the carina showed unusual horizontal
      orientation making it difficult to identify the fistula. However, a post mortem
      CT confirmed the diagnosis of an isolated Type II tracheal agenesis with
      bronchoesophageal fistula.

PMID- 22363178
TI  - Severe emphysematous cystitis: Outcome after seven days of antibiotics.
AB  - We present the case of a 70-year-old woman with emphysematous cystitis. She was a
      diabetic patient and she was on chemotherapy treatment for a breast cancer. She
      complaint of severe asthenia and pain in her right lower extremity, but no fever
      or urinary symptoms. A computed tomography (CT) scan was suggestive of severe
      emphysematous cystitis. Emphysematous cystitis is a rare clinically entity, more
      commonly seen in diabetic, immunocompromised patients. A conservative treatment
      approach using antibiotics and bladder catheterization is typically successful,
      with a complication rate less than 20%.

PMID- 22363179
TI  - A rare variant of a common nodule.

PMID- 22363180
TI  - Use of fresh osteochondral allograft in repair of distal femur after trauma.
AB  - Preserving the ability to maintain an active lifestyle is a major concern in the
      reconstruction of the knee in young patients. For the healthy individual who
      desires to maintain a relatively active lifestyle, fresh osteochondral allografts
      may serve as an alternative to total joint reconstruction. The use of fresh
      allografts is primarily indicated in the patient suffering from a traumatic loss
      of articular segments, who is too young or active for arthroplasty. In addition,
      fresh osteochondral allografts have a number of advantages over arthroplasty such
      as providing surgeons with a source of large grafts that can be fitted to replace
      osteochondral defects and cover the majority or entirety of articular surfaces
      without any donor site morbidity. In this case, a young, active patient lost a 7
      x 8 cm portion of their distal femur, including a large portion of the
      articulating surface. Using a fresh osteochondral allograft, harvested within 24
      hours of donor death, a segment was fitted to match bony apposition, articular
      congruity, and congruity with the femoral notch and affixed with four partially
      threaded cancellous screws. Joint function was restored with the allograft in
      place, allowing the patient to delay the need for a total joint replacement.

PMID- 22363181
TI  - Crohn's disease presenting with atypical mucocutaneous lesions in an 11 year old
      boy.

PMID- 22363182
TI  - The effects of cognitive therapy on hallucinations in patients with
      schizophrenia.

PMID- 22363183
TI  - Engineering alloplastic temporomandibular joint replacements.
AB  - Temporomandibular disorders (TMD) are part of a heterogeneous group of
      pathologies that manifest with a constellation of signs and symptoms. They are
      the most frequent cause of chronic orofacial pain and are prevalent in 12% of the
      general population. Despite the debilitating nature of these disorders, there is
      no standardization for treatment of the diseased temporomandibular joint (TMJ).
      In this review, we present an overview of the functional anatomy of the TMJ and
      the engineering concepts that must be understood to better understand the
      indications for surgical management, the types of available treatments and the
      requirements for reconstruction. A comparison is made of the clinical outcomes
      with autogenous versus alloplastic reconstruction, including a history of
      alloplastic materials and the design features of currently available implants.
      Emphasis is made on material selection, modulus, stiffness, notch sensitivity and
      modularity. For the treatment of TMD, engineered TMJ alloplastic replacements
      have had considerable promise with additional room for improvement using new
      materials and recent design concepts.

PMID- 22363184
TI  - Anthropology's Contribution to Public Health Policy Development.

PMID- 22363185
TI  - The United states' health care reform bill - a translation.

PMID- 22363186
TI  - An examination of the factors contributing to poor communication outside the
      physician-patient sphere.

PMID- 22363187
TI  - The Final Frontier: A medical student's mission to boldly dream where no dream
      has gone before.

PMID- 22363188
TI  - Kienbock's disease and juvenile idiopathic arthritis.
AB  - Kienbock's disease or osteonecrosis of the lunate is an uncommon cause of wrist
      pain. . Though there have been several reports of cases in patients with various
      rheumatologic diseases, the precise etiology has currently not been established.
      We report a case of Kienbock's disease that occurred in a patient with juvenile
      idiopathic arthritis. To our knowledge, this is the first case report with an
      association between these two conditions.

PMID- 22363189
TI  - A new palmo-shoulder compression association.

PMID- 22363190
TI  - Teenage female with knee pain and instability.

PMID- 22363191
TI  - A man with a neck mass, pleural effusion and hypoechoic masses in the right
      atrium and ventricle.

PMID- 22363192
TI  - Salvage Resection for Isolated Local and/or Regional Failure of Head/Neck Cancer
      Following Definitive Concurrent Chemoradiotherapy Case Series and Review of the
      Literature.
AB  - BACKGROUND: Primary management of advanced head/neck cancers involves concurrent
      chemoradiotherapy . Subsequently, regional and local failures are managed with
      resection but there have been few reports that describe the morbidity and disease
      control outcomes of surgical salvage in this setting. METHODS: Retrospective
      analysis describes complications, survival, and patterns of failure after salvage
      resection of isolated local and/or regional failures of head/neck cancer
      following definitive concurrent chemoradiotherapy. RESULTS: Sixteen patients were
      identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx
      resection in 2 patients, and neck dissection alone in 4 patients. Ten patients
      required graft tissue reconstruction (6 pedicle and 4 free flap). Median post
      operative hospitalization was 7 days (range 3-19), and 4 patients required
      hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3
      34.9), 10 patients were alive (6 without evidence of disease). Seven patients
      experienced disease recurrence at a median 6.7 months (range 0-12.6) following
      salvage resection (2 with isolated distant failures). Estimated 2-year
      local/regional control, freedom from failure, and overall survival were 58%, 39%,
      and 58%, respectively. CONCLUSIONS: Surgical salvage after primary definitive
      concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to
      prior radiotherapy alone or sequential chemotherapy and radiation. Local
      andregional recurrence remains the predominant pattern of failure.

PMID- 22363194
TI  - Breaking the Scope-of-Practice Taboo: Where Multidisciplinary Rhymes with Cost
      Efficiency.

PMID- 22363193
TI  - Evolutionary approaches to autism- an overview and integration.
AB  - Autism is a highly heritable neurodevelopmental disorder, which greatly reduces
      reproductive success. The combination of high heritability and low reproductive
      success raises an evolutionary question: why was autism not eliminated by natural
      selection? We review different perspectives on the evolution of autism and
      propose an integration which emphasizes epistatic interactions between the
      effects of genes during development. It is well-established that autism is a
      polygenic disorder, and that the genes contributing to autism interact. If a
      disorder is polygenic, it is likely that the genes underlying the disorder are
      also involved in traits that are beneficial for the individual. For example, it
      is possible that genes involved in the development of autism are also involved in
      the development of intelligence. As intelligence is positively correlated with
      reproductive success, genes involved in autism can possibly spread in the
      population. We propose that in most individuals, the interactions between genes
      result in normal or high intelligence and the absence of autism. However, in some
      unlucky situations, often in combination with spontaneous negative mutations, the
      interactions between genes can lead to the development of autism (or other
      pathologies). Thus, the combination of high heritability and low reproductive
      success in autism can be explained from an evolutionary developmental perspective
      that emphasizes the role of epistatic interactions in polygenic disorders.

PMID- 22363195
TI  - The canadian space agency space learning grants.

PMID- 22363197
TI  - Medical care in the arctic and on orbit.

PMID- 22363198
TI  - Physicians as astronauts.

PMID- 22363196
TI  - Medical Education for Exploration Class Missions NASA Aerospace Medicine Elective
      at the Kennedy Space Centre.

PMID- 22363199
TI  - Human space exploration the next fifty years.
AB  - Preparation for the fiftieth anniversary of human spaceflight in the spring of
      2011 provides the space faring nations with an opportunity to reflect on past
      achievements as well as consider the next fifty years of human spaceflight. The
      International Space Station is a unique platform for long duration life science
      research that will play a critical role in preparing for future human space
      exploration beyond low earth orbit. Some feel the future path back to the Moon
      and on to Mars may be delayed with the current commitment of the United States to
      support the development of human-rated commercial spacecraft. Others see this as
      a unique opportunity to leverage the capability of the private sector in
      expanding access to space exploration. This article provides an overview of the
      past achievements in human spaceflight and discusses future missions over the
      next fifty years and the role space medicine will play in extending the time
      distance constant of human space exploration.

PMID- 22363200
TI  - Exploring the possibility for a common system for joint aeromedical standards.
AB  - The Physical qualification standards for aviation service used by the United
      States Army, Navy/Marine Corps, Air Force, and Coast Guard developed in parallel,
      diverging in many instances due to differences ranging from terminology to
      mission. Presently, standards and requirements for waiver vary widely between the
      services, in spite of minimal differences in aeromedical concerns for any given
      medical condition. Standardization or increased concordance between the services
      would have several advantages leading to more efficient and effective delivery of
      aviation medical support to the operational forces. This is particularly true in
      an increasingly joint operational environment. The authors have identified four
      major hurdles that must be overcome before the concept of joint aviation physical
      standards can be explored. These include: a difference in terminology including
      aviator classification, a difference in mission definitions and requirements, a
      difference in the processes of policy development, and a difference in the review
      and application of those policies. These hurdles are explored, and suggestions
      for their mitigation are presented with open discussion following.

PMID- 22363201
TI  - Systematics, conservation and morphology of the spider genus Tayshaneta (Araneae,
      Leptonetidae) in Central Texas Caves.
AB  - The spider genus Tayshaneta is revised based on results from a three gene
      phylogenetic analysis (Ledford et al. 2011) and a comprehensive morphological
      survey using scanning electron (SEM) and compound light microscopy. The
      morphology and relationships within Tayshaneta are discussed and five species
      groups are supported by phylogenetic analyses: the anopica group, the coeca
      group, the myopica group, the microps group and the sandersi group. Short branch
      lengths within Tayshaneta contrast sharply with the remaining North American
      genera and are viewed as evidence for a relatively recent radiation of species.
      Variation in troglomorphic morphology is discussed and compared to patterns found
      in other Texas cave invertebrates. Several species previously known as single
      cave endemics have wider ranges than expected, suggesting that some caves are not
      isolated habitats but instead form part of interconnected karst networks.
      Distribution maps are compared with karst faunal regions (KFR's) in Central Texas
      and the implications for the conservation and recovery of Tayshaneta species are
      discussed. Ten new species are described: Tayshaneta archambaultisp. n.,
      Tayshaneta emeraldaesp. n., Tayshaneta fawcettisp. n., Tayshaneta grubbsisp. n.,
      Tayshaneta madlasp. n., Tayshaneta oconnoraesp. n., Tayshaneta sandersisp. n.,
      Tayshaneta sprouseisp. n., Tayshaneta vidriosp. n. and Tayshaneta whiteisp. n.
      The males for three species, Tayshaneta anopica (Gertsch, 1974), Tayshaneta devia
      (Gertsch, 1974) and Tayshaneta microps (Gertsch, 1974) are described for the
      first time. Tayshaneta furtiva (Gertsch, 1974) and Tayshaneta uvaldea (Gertsch,
      1974) are declared nomina dubia as the female holotypes are not diagnosable and
      efforts to locate specimens at the type localities were unsuccessful. All
      Tayshaneta species are thoroughly illustrated, diagnosed and keyed. Distribution
      maps are also provided highlighting areas of taxonomic ambiguity in need of
      additional sampling.

PMID- 22363202
TI  - High-resolution melting analysis for SNP genotyping and mapping in tetraploid
      alfalfa (Medicago sativa L.).
AB  - Single nucleotide polymorphisms (SNPs) represent the most abundant type of
      genetic polymorphism in plant genomes. SNP markers are valuable tools for genetic
      analysis of complex traits of agronomic importance, linkage and association
      mapping, genome-wide selection, map-based cloning, and marker-assisted selection.
      Current challenges for SNP genotyping in polyploid outcrossing species include
      multiple alleles per loci and lack of high-throughput methods suitable for
      variant detection. In this study, we report on a high-resolution melting (HRM)
      analysis system for SNP genotyping and mapping in outcrossing tetraploid
      genotypes. The sensitivity and utility of this technology is demonstrated by
      identification of the parental genotypes and segregating progeny in six alfalfa
      populations based on unique melting curve profiles due to differences in allelic
      composition at one or multiple loci. HRM using a 384-well format is a fast,
      consistent, and efficient approach for SNP discovery and genotyping, useful in
      polyploid species with uncharacterized genomes. Possible applications of this
      method include variation discovery, analysis of candidate genes, genotyping for
      comparative and association mapping, and integration of genome-wide selection in
      breeding programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s11032-011-9566-x) contains supplementary material, which is
      available to authorized users.

PMID- 22363203
TI  - GPCA vs. PCA in recognition and 3-D localization of ultrasound reflectors.
AB  - In this paper, a new method of classification and localization of reflectors,
      using the time-of-flight (TOF) data obtained from ultrasonic transducers, is
      presented. The method of classification and localization is based on Generalized
      Principal Component Analysis (GPCA) applied to the TOF values obtained from a
      sensor that contains four ultrasound emitters and 16 receivers. Since PCA works
      with vectorized representations of TOF, it does not take into account the spatial
      locality of receivers. The GPCA works with two-dimensional representations of
      TOF, taking into account information on the spatial position of the receivers.
      This report includes a detailed description of the method of classification and
      localization and the results of achieved tests with three types of reflectors in
      3-D environments: planes, edges, and corners. The results in terms of processing
      time, classification and localization were very satisfactory for the reflectors
      located in the range of 50-350 cm.

PMID- 22363204
TI  - Location estimation in wireless sensor networks using spring-relaxation
      technique.
AB  - Accurate and low-cost autonomous self-localization is a critical requirement of
      various applications of a large-scale distributed wireless sensor network (WSN).
      Due to its massive deployment of sensors, explicit measurements based on
      specialized localization hardware such as the Global Positioning System (GPS) is
      not practical. In this paper, we propose a low-cost WSN localization solution.
      Our design uses received signal strength indicators for ranging, light weight
      distributed algorithms based on the spring-relaxation technique for location
      computation, and the cooperative approach to achieve certain location estimation
      accuracy with a low number of nodes with known locations. We provide analysis to
      show the suitability of the spring-relaxation technique for WSN localization with
      cooperative approach, and perform simulation experiments to illustrate its
      accuracy in localization.

PMID- 22363205
TI  - Histone deacetylase complexes promote trinucleotide repeat expansions.
AB  - Expansions of DNA trinucleotide repeats cause at least 17 inherited
      neurodegenerative diseases, such as Huntington's disease. Expansions can occur at
      frequencies approaching 100% in affected families and in transgenic mice,
      suggesting that specific cellular proteins actively promote (favor) expansions.
      The inference is that expansions arise due to the presence of these promoting
      proteins, not their absence, and that interfering with these proteins can
      suppress expansions. The goal of this study was to identify novel factors that
      promote expansions. We discovered that specific histone deacetylase complexes
      (HDACs) promote CTG*CAG repeat expansions in budding yeast and human cells.
      Mutation or inhibition of yeast Rpd3L or Hda1 suppressed up to 90% of expansions.
      In cultured human astrocytes, expansions were suppressed by 75% upon inhibition
      or knockdown of HDAC3, whereas siRNA against the histone acetyltransferases
      CBP/p300 stimulated expansions. Genetic and molecular analysis both indicated
      that HDACs act at a distance from the triplet repeat to promote expansions.
      Expansion assays with nuclease mutants indicated that Sae2 is one of the relevant
      factors regulated by Rpd3L and Hda1. The causal relationship between HDACs and
      expansions indicates that HDACs can promote mutagenesis at some DNA sequences.
      This relationship further implies that HDAC3 inhibitors being tested for relief
      of expansion-associated gene silencing may also suppress somatic expansions that
      contribute to disease progression.

PMID- 22363206
TI  - Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for
      cognitive enhancement.
AB  - Cell adhesion molecules and downstream growth factor-dependent signaling are
      critical for brain development and synaptic plasticity, and they have been linked
      to cognitive function in adult animals. We have previously developed a mimetic
      peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial
      learning and memory in rats. We have now investigated the cellular and molecular
      basis of this cognitive enhancement, using biochemical, morphological,
      electrophysiological, and behavioral analyses. We have found that FGL triggers a
      long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons.
      This effect is mediated by a facilitated synaptic delivery of AMPA receptors,
      which is accompanied by enhanced NMDA receptor-dependent long-term potentiation
      (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC
      activation, which is followed by persistent CaMKII activation. These results
      provide a mechanistic link between facilitation of AMPA receptor synaptic
      delivery and improved hippocampal-dependent learning, induced by a
      pharmacological cognitive enhancer.

PMID- 22363207
TI  - Patterns of gene flow define species of thermophilic Archaea.
AB  - Despite a growing appreciation of their vast diversity in nature, mechanisms of
      speciation are poorly understood in Bacteria and Archaea. Here we use high
      throughput genome sequencing to identify ongoing speciation in the
      thermoacidophilic Archaeon Sulfolobus islandicus. Patterns of homologous gene
      flow among genomes of 12 strains from a single hot spring in Kamchatka, Russia,
      demonstrate higher levels of gene flow within than between two persistent,
      coexisting groups, demonstrating that these microorganisms fit the biological
      species concept. Furthermore, rates of gene flow between two species are
      decreasing over time in a manner consistent with incipient speciation. Unlike
      other microorganisms investigated, we do not observe a relationship between
      genetic divergence and frequency of recombination along a chromosome, or other
      physical mechanisms that would reduce gene flow between lineages. Each species
      has its own genetic island encoding unique physiological functions and a unique
      growth phenotype that may be indicative of ecological specialization. Genetic
      differentiation between these coexisting groups occurs in large genomic
      "continents," indicating the topology of genomic divergence during speciation is
      not uniform and is not associated with a single locus under strong diversifying
      selection. These data support a model where species do not require physical
      barriers to gene flow but are maintained by ecological differentiation.

PMID- 22363209
TI  - Enzyme inhibitor may offer dual protection against brain disease.

PMID- 22363208
TI  - Neural mechanisms underlying motivation of mental versus physical effort.
AB  - Mental and physical efforts, such as paying attention and lifting weights, have
      been shown to involve different brain systems. These cognitive and motor systems,
      respectively, include cortical networks (prefronto-parietal and precentral
      regions) as well as subregions of the dorsal basal ganglia (caudate and putamen).
      Both systems appeared sensitive to incentive motivation: their activity increases
      when we work for higher rewards. Another brain system, including the ventral
      prefrontal cortex and the ventral basal ganglia, has been implicated in encoding
      expected rewards. How this motivational system drives the cognitive and motor
      systems remains poorly understood. More specifically, it is unclear whether
      cognitive and motor systems can be driven by a common motivational center or if
      they are driven by distinct, dedicated motivational modules. To address this
      issue, we used functional MRI to scan healthy participants while performing a
      task in which incentive motivation, cognitive, and motor demands were varied
      independently. We reasoned that a common motivational node should (1) represent
      the reward expected from effort exertion, (2) correlate with the performance
      attained, and (3) switch effective connectivity between cognitive and motor
      regions depending on task demand. The ventral striatum fulfilled all three
      criteria and therefore qualified as a common motivational node capable of driving
      both cognitive and motor regions of the dorsal striatum. Thus, we suggest that
      the interaction between a common motivational system and the different task
      specific systems underpinning behavioral performance might occur within the basal
      ganglia.

PMID- 22363210
TI  - Anything you can do, you can do better: neural substrates of incentive-based
      performance enhancement.
AB  - Performance-based pay schemes in many organizations share the fundamental
      assumption that the performance level for a given task will increase as a
      function of the amount of incentive provided. Consistent with this notion,
      psychological studies have demonstrated that expectations of reward can improve
      performance on a plethora of different cognitive and physical tasks, ranging from
      problem solving to the voluntary regulation of heart rate. However, much less is
      understood about the neural mechanisms of incentivized performance enhancement.
      In particular, it is still an open question how brain areas that encode
      expectations about reward are able to translate incentives into improved
      performance across fundamentally different cognitive and physical task
      requirements.

PMID- 22363211
TI  - The activities of current antimalarial drugs on the life cycle stages of
      Plasmodium: a comparative study with human and rodent parasites.
AB  - BACKGROUND: Malaria remains a disease of devastating global impact, killing more
      than 800,000 people every year-the vast majority being children under the age of
      5. While effective therapies are available, if malaria is to be eradicated a
      broader range of small molecule therapeutics that are able to target the liver
      and the transmissible sexual stages are required. These new medicines are needed
      both to meet the challenge of malaria eradication and to circumvent resistance.
      METHODS AND FINDINGS: Little is known about the wider stage-specific activities
      of current antimalarials that were primarily designed to alleviate symptoms of
      malaria in the blood stage. To overcome this critical gap, we developed assays to
      measure activity of antimalarials against all life stages of malaria parasites,
      using a diverse set of human and nonhuman parasite species, including male gamete
      production (exflagellation) in Plasmodium falciparum, ookinete development in P.
      berghei, oocyst development in P. berghei and P. falciparum, and the liver stage
      of P. yoelii. We then compared 50 current and experimental antimalarials in these
      assays. We show that endoperoxides such as OZ439, a stable synthetic molecule
      currently in clinical phase IIa trials, are strong inhibitors of gametocyte
      maturation/gamete formation and impact sporogony; lumefantrine impairs
      development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits
      sporogony. CONCLUSIONS: These data enable objective comparisons of the strengths
      and weaknesses of each chemical class at targeting each stage of the lifecycle.
      Noting that the activities of many compounds lie within achievable blood
      concentrations, these results offer an invaluable guide to decisions regarding
      which drugs to combine in the next-generation of antimalarial drugs. This study
      might reveal the potential of life-cycle-wide analyses of drugs for other
      pathogens with complex life cycles.

PMID- 22363212
TI  - Mobile phone text messaging: tool for malaria control in Africa.

PMID- 22363214
TI  - Tuberculosis and HIV co-infection.
AB  - Tuberculosis (TB) and HIV co-infections place an immense burden on health care
      systems and pose particular diagnostic and therapeutic challenges. Infection with
      HIV is the most powerful known risk factor predisposing for Mycobacterium
      tuberculosis infection and progression to active disease, which increases the
      risk of latent TB reactivation 20-fold. TB is also the most common cause of AIDS
      related death. Thus, M. tuberculosis and HIV act in synergy, accelerating the
      decline of immunological functions and leading to subsequent death if untreated.
      The mechanisms behind the breakdown of the immune defense of the co-infected
      individual are not well known. The aim of this review is to highlight
      immunological events that may accelerate the development of one of the two
      diseases in the presence of the co-infecting organism. We also review possible
      animal models for studies of the interaction of the two pathogens, and describe
      gaps in knowledge and needs for future studies to develop preventive measures
      against the two diseases.

PMID- 22363215
TI  - Nondisjunction of a single chromosome leads to breakage and activation of DNA
      damage checkpoint in G2.
AB  - The resolution of chromosomes during anaphase is a key step in mitosis. Failure
      to disjoin chromatids compromises the fidelity of chromosome inheritance and
      generates aneuploidy and chromosome rearrangements, conditions linked to cancer
      development. Inactivation of topoisomerase II, condensin, or separase leads to
      gross chromosome nondisjunction. However, the fate of cells when one or a few
      chromosomes fail to separate has not been determined. Here, we describe a genetic
      system to induce mitotic progression in the presence of nondisjunction in yeast
      chromosome XII right arm (cXIIr), which allows the characterisation of the
      cellular fate of the progeny. Surprisingly, we find that the execution of
      karyokinesis and cytokinesis is timely and produces severing of cXIIr on or near
      the repetitive ribosomal gene array. Consequently, one end of the broken
      chromatid finishes up in each of the new daughter cells, generating a novel type
      of one-ended double-strand break. Importantly, both daughter cells enter a new
      cycle and the damage is not detected until the next G2, when cells arrest in a
      Rad9-dependent manner. Cytologically, we observed the accumulation of damage foci
      containing RPA/Rad52 proteins but failed to detect Mre11, indicating that cells
      attempt to repair both chromosome arms through a MRX-independent recombinational
      pathway. Finally, we analysed several surviving colonies arising after just one
      cell cycle with cXIIr nondisjunction. We found that aberrant forms of the
      chromosome were recovered, especially when RAD52 was deleted. Our results
      demonstrate that, in yeast cells, the Rad9-DNA damage checkpoint plays an
      important role responding to compromised genome integrity caused by mitotic
      nondisjunction.

PMID- 22363213
TI  - Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control
      studies, avoiding publication bias.
AB  - BACKGROUND: Moderately elevated blood levels of homocysteine are weakly
      correlated with coronary heart disease (CHD) risk, but causality remains
      uncertain. When folate levels are low, the TT genotype of the common C677T
      polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR)
      appreciably increases homocysteine levels, so "Mendelian randomization" studies
      using this variant as an instrumental variable could help test causality. METHODS
      AND FINDINGS: Nineteen unpublished datasets were obtained (total 48,175 CHD cases
      and 67,961 controls) in which multiple genetic variants had been measured,
      including MTHFR C677T. These datasets did not include measurements of blood
      homocysteine, but homocysteine levels would be expected to be about 20% higher
      with TT than with CC genotype in the populations studied. In meta-analyses of
      these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI
      comparing TT versus CC homozygotes was 1.02 (0.98-1.07; p = 0.28) overall, and
      1.01 (0.95-1.07) in unsupplemented low-folate populations. By contrast, in a
      slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and
      41,857 controls), the OR was 1.15 (1.09-1.21), significantly discrepant (p =
      0.001) with the OR in the unpublished datasets. Within the meta-analysis of
      published studies, the OR was 1.12 (1.04-1.21) in the 14 larger studies (those
      with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09-1.28) in the 72
      smaller ones (total 15,498 cases). CONCLUSIONS: The CI for the overall result
      from large unpublished datasets shows lifelong moderate homocysteine elevation
      has little or no effect on CHD. The discrepant overall result from previously
      published studies reflects publication bias or methodological problems.

PMID- 22363216
TI  - GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is
      regulated by ArfGAP1.
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common
      cause of autosomal dominant familial Parkinson's disease (PD) and also contribute
      to idiopathic PD. LRRK2 encodes a large multi-domain protein with GTPase and
      kinase activity. Initial data indicates that an intact functional GTPase domain
      is critically required for LRRK2 kinase activity. PD-associated mutations in
      LRRK2, including the most common G2019S variant, have variable effects on
      enzymatic activity but commonly alter neuronal process morphology. The mechanisms
      underlying the intrinsic and extrinsic regulation of LRRK2 GTPase and kinase
      activity, and the pathogenic effects of familial mutations, are incompletely
      understood. Here, we identify a novel functional interaction between LRRK2 and
      ADP-ribosylation factor GTPase-activating protein 1 (ArfGAP1). LRRK2 and ArfGAP1
      interact in vitro in mammalian cells and in vivo in brain, and co-localize in the
      cytoplasm and at Golgi membranes. PD-associated and functional mutations that
      alter the GTPase activity of LRRK2 modulate the interaction with ArfGAP1. The GTP
      hydrolysis activity of LRRK2 is markedly enhanced by ArfGAP1 supporting a role
      for ArfGAP1 as a GTPase-activating protein for LRRK2. Unexpectedly, ArfGAP1
      promotes the kinase activity of LRRK2 suggesting a potential role for GTP
      hydrolysis in kinase activation. Furthermore, LRRK2 robustly and directly
      phosphorylates ArfGAP1 in vitro. Silencing of ArfGAP1 expression in primary
      cortical neurons rescues the neurite shortening phenotype induced by G2019S LRRK2
      overexpression, whereas the co-expression of ArfGAP1 and LRRK2 synergistically
      promotes neurite shortening in a manner dependent upon LRRK2 GTPase activity.
      Neurite shortening induced by ArfGAP1 overexpression is also attenuated by
      silencing of LRRK2. Our data reveal a novel role for ArfGAP1 in regulating the
      GTPase activity and neuronal toxicity of LRRK2; reciprocally, LRRK2
      phosphorylates ArfGAP1 and is required for ArfGAP1 neuronal toxicity. ArfGAP1 may
      represent a promising target for interfering with LRRK2-dependent
      neurodegeneration in familial and sporadic PD.

PMID- 22363217
TI  - Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and
      stimulates apoptosis in mouse melanoma B16F10 cell line.
AB  - Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural
      product. In our previous work, we reported the significant chemopreventive
      effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse
      models. In this investigation, we extended this work to study the effect of
      sarcodiol on melanoma development, the more deadly form of skin cancer, using the
      mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de
      novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the
      antitumor effect of SD on melanoma cell viability using several biomarkers for
      cell proliferation and apoptosis. SD inhibits the expression levels of signal
      transducers and activators of transcription protein (STAT-3) and cyclin D1, an
      activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances
      cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of
      the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances
      cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities
      of Caspase-3, -8 and -9. These results, in addition to inhibition of cell
      viability, suggest that SD inhibits melanoma cell proliferation by arresting the
      cell-division cycle in a Go quiescent phase and activates programmed cell death
      (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies
      demonstrate that SD shows a very promising chemopreventive effect in melanoma
      B16F10 tumor cells.

PMID- 22363218
TI  - A chronic oral toxicity study of marine collagen peptides preparation from chum
      salmon (Oncorhynchus keta) skin using Sprague-Dawley rat.
AB  - Due to the increased consumption of marine collagen peptides preparation (MCP) as
      ingredients in functional foods and pharmaceuticals, it was necessary to carry
      out safety requirements in the form of an oral chronic toxicity assessment. In
      order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP
      was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes
      were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18%
      (wt/wt). The actual food intake and bodyweight of the individual animals were
      recorded periodically until sacrifice. Blood and urine samples were collected for
      serum chemistry evaluations and urinalysis. Throughout the experimental period,
      there was no toxicologically significant difference between the vehicle and MCP
      treated animals with respect to the survival rate, body weight, food consumption,
      urinalysis, clinical biochemistry parameter and relative organ weight in either
      sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not
      significantly increase compared with the control group. Under the present
      experimental conditions, no higher risk of chronic toxic effects was observed in
      MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt)
      than in the rats fed with basal rodent diet.

PMID- 22363219
TI  - Purification, characterization and antitumor activities of a new protein from
      Syngnathus acus, an officinal marine fish.
AB  - Discovery and development of new antitumor agents from abundant marine fish are
      attracting an increasing interest. In the present study, we extracted and
      purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus
      acus L., a precious marine fish traditionally used for tumors. Syngnathusin was
      comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular
      weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid
      sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu
      Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins.
      Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells.
      However, the obvious proliferation inhibition against human non-tumor cell lines
      was not observed. Flow cytometry, morphologic assessment and comet assay revealed
      that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly
      cooperated with MTX. Syngnathusin could inhibit the growth of S180 tumor
      transplanted in mice. Syngnathusin may be developed as a novel, selective and
      effective antineoplastic agent.

PMID- 22363220
TI  - Aplisulfamines, new sulfoxide-containing metabolites from an aplidium tunicate:
      absolute stereochemistry at chiral sulfur and carbon atoms assigned through an
      original combination of spectroscopic and computational methods.
AB  - Two new sulfoxide-containing metabolites, aplisulfamines A and B, have been
      isolated from an Aplidium sp. collected in the Bay of Naples. Their planar
      structure and geometry of a double bond were readily determined by using standard
      methods, mainly NMR spectroscopy. An original approach was used to assign the
      absolute configuration at the three contiguous chiral centers present in the
      structures of both aplisulfamines, two at carbon and one at sulfur. This involved
      Electronic Circular Dichroism (ECD) studies, J-based configuration analysis and
      Density Functional Theory (DFT) calculations and represents an interesting
      integration of modern techniques in stereoanalysis, which could contribute to the
      enhancement of theoretical protocols recently applied to solve stereochemical
      aspects in structure elucidation.

PMID- 22363221
TI  - Marine compounds selectively induce apoptosis in female reproductive cancer cells
      but not in primary-derived human reproductive granulosa cells.
AB  - Anticancer properties of tyrindoleninone and 6-bromoisatin from Dicathais orbita
      were tested against physiologically normal primary human granulosa cells (HGC)
      and reproductive cancer cell lines. Tyrindoleninone reduced cancer cell viability
      with IC50 values of 39 uM (KGN; a tumour-derived granulosa cell line), 39 MUM
      (JAr), and 156 MUM (OVCAR-3), compared to 3516 MUM in HGC. Apoptosis in HGC's
      occurred after 4 h at 391 uM tyrindoleninone compared to 20 uM in KGN cells.
      Differences in apoptosis between HGC and KGN cells were confirmed by TUNEL, with
      66 and 31% apoptotic nuclei at 4 h in KGN and HGC, respectively. These marine
      compounds therefore have potential for development as treatments for female
      reproductive cancers.

PMID- 22363222
TI  - Tasco(r): a product of Ascophyllum nodosum enhances immune response of
      Caenorhabditis elegans against Pseudomonas aeruginosa infection.
AB  - The effects of Tasco(r), a product made from the brown seaweed (Ascophyllum
      nodosum) were tested for the ability to protect Caenorhabditis elegans against
      Pseudomonas aeruginosa infection. A water extract of Tasco(r) (TWE) reduced P.
      aeruginosa inflicted mortality in the nematode. The TWE, at a concentration of
      300 ug/mL, offered the maximum protection and induced the expression of innate
      immune response genes viz.; zk6.7 (Lypases), lys-1 (Lysozyme), spp-1 (Saponin
      like protein), f28d1.3 (Thaumatin like protein), t20g5.7 (Matridin SK domain
      protein), abf-1 (Antibacterial protein) and f38a1.5 (Lectin family protein).
      Further, TWE treatment also affected a number of virulence components of the P.
      aeuroginosa and reduced its secreted virulence factors such as lipase, proteases
      and toxic metabolites; hydrogen cyanide and pyocyanin. Decreased virulence
      factors were associated with a significant reduction in expression of regulatory
      genes involved in quorum sensing, lasI, lasR, rhlI and rhlR. In conclusion, the
      TWE-treatment protected the C. elegans against P. aeruginosa infection by a
      combination of effects on the innate immunity of the worms and direct effects on
      the bacterial quorum sensing and virulence factors.

PMID- 22363223
TI  - A new cytotoxic sesquiterpene quinone produced by Penicillium sp. F00120 isolated
      from a deep sea sediment sample.
AB  - A new fungal strain, displaying strong toxic activity against brine shrimp
      larvae, was isolated from a deep sea sediment sample collected at a depth of 1300
      m. The strain, designated as F00120, was identified as a member of the genus
      Penicillium on the basis of morphology and ITS sequence analysis. One new
      sesquiterpene quinone, named penicilliumin A (1), along with two known compounds
      ergosterol (2) and ergosterol peroxide (3), were isolated and purified from the
      cultures of F00120 by silica gel column, Sephadex LH-20 column, and preparative
      thin layer chromatography. Their structures were elucidated by detailed nuclear
      magnetic resonance (NMR) and mass spectroscopic (MS) analysis as well as
      comparison with literature data. The new compound penicilliumin A inhibited in
      vitro proliferation of mouse melanoma (B16), human melanoma (A375), and human
      cervical carcinoma (Hela) cell lines moderately.

PMID- 22363224
TI  - Marine carotenoids and oxidative stress.
AB  - Oxidative stress induced by reactive oxygen species plays an important role in
      the etiology of many diseases. Dietary phytochemical products, such as bioactive
      food components and marine carotenoids (asthaxantin, lutein, beta-carotene,
      fucoxanthin), have shown an antioxidant effect in reducing oxidative markers
      stress. Scientific evidence supports the beneficial role of phytochemicals in the
      prevention of some chronic diseases. Many carotenoids with high antioxidant
      properties have shown a reduction in disease risk both in epidemiological studies
      and supplementation human trials. However, controlled clinical trials and dietary
      intervention studies using well-defined subjects population have not provided
      clear evidence of these substances in the prevention of diseases. The most
      important aspects of this special issue will cover the synthesis, biological
      activities, and clinical applications of marine carotenoids, with particular
      attention to recent evidence regarding anti-oxidant and anti-inflammatory
      properties in the prevention of cardiovascular disease.

PMID- 22363225
TI  - Antioxidant properties of polysaccharide from the brown seaweed Sargassum
      graminifolium (Turn.), and its effects on calcium oxalate crystallization.
AB  - We investigated the effects of polysaccharides from the brown seaweed Sargassum
      graminifolium (Turn.) (SGP) on calcium oxalate crystallization, and determined
      its antioxidant activities. To examine the effects of SGP on calcium oxalate
      crystallization, we monitored nucleation and aggregation of calcium oxalate
      monohydrate crystals, using trisodium citrate as a positive control. We assessed
      antioxidant activities of SGP by determining its reducing power, its ability to
      scavenge superoxide radicals, and its activity in the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay. The nucleation inhibition ratio of trisodium citrate
      and SGP was 58.5 and 69.2%, respectively, and crystal aggregation was inhibited
      by 71.4 and 76.8%, respectively. Increasing concentrations of SGP resulted in
      increased scavenging of superoxide anions and DPPH radicals (IC50 = 1.9 and 0.6
      mg/mL, respectively). These results suggest that SGP could be a candidate for
      treating urinary stones because of its ability to inhibit calcium oxalate
      crystallization and its antioxidant properties.

PMID- 22363226
TI  - Secondary metabolites from an algicolous Aspergillus versicolor strain.
AB  - Two new compounds, asperversin A (1) and 9xi-O-2(2,3-dimethylbut-3
      enyl)brevianamide Q (2), and nine known compounds, brevianamide K (3),
      brevianamide M (4), aversin (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O
      methylaverufin (7), 6-O-methylaverufin (8), 5alpha,8alpha-epidioxyergosta-6,22
      dien-3beta-ol (9), ergosta-7,22-diene-3beta,5alpha,6beta-triol (10), and 6beta
      methoxyergosta-7,22-diene-3beta,5alpha-diol (11), were obtained from the culture
      of Aspergillus versicolor, an endophytic fungus isolated from the marine brown
      alga Sargassum thunbergii. The structures of these compounds were established by
      spectroscopic techniques. Compounds 4, 7 and 8 exhibited antibacterial activities
      against Escherichia coli and Staphyloccocus aureus, and 7 also showed lethality
      against brine shrimp (Artemia salina) with an LC50 value of 0.5 MUg/mL.

PMID- 22363228
TI  - Tetrodotoxin concentrations in Pleurobranchaea maculata: temporal, spatial and
      individual variability from New Zealand populations.
AB  - Tetrodotoxin (TTX) is a potent neurotoxin that has been identified in a range of
      phylogenetically unrelated marine and terrestrial organisms. Tetrodotoxin was
      recently detected in New Zealand in Pleurobranchaea maculata (the grey side
      gilled sea slug). From June 2010 to June 2011 wild specimens were collected from
      10 locations around New Zealand. At one site (Narrow Neck Beach, Auckland) up to
      10 individuals were collected monthly for 6 months. Attempts were also made to
      rear P. maculata in captivity. Tetrodotoxin was detected in samples from eight of
      the ten sites. The highest average (368.7 mg kg-1) and maximum (1414.0 mg kg-1)
      concentrations were measured in samples from Illiomama Rock (Auckland). Of the
      toxic populations tested there was significant variability in TTX concentrations
      among individuals, with the highest difference (62 fold) measured at Illiomama
      Rock. Tetrodotoxin concentrations in samples from Narrow Neck Beach varied
      temporally, ranging from an average of 184 mg kg-1 in June 2010 to 17.5 mg kg-1
      by December 2010. There was no correlation between TTX levels and mass. The
      highest levels correspond with the egg laying season (June-August) and this, in
      concert with the detection of high levels of TTX in eggs and early larval stages,
      suggests that TTX may have a defensive function in P. maculata. Only one larva
      was successfully reared to full maturation and no TTX was detected.

PMID- 22363227
TI  - Toxin levels and profiles in microalgae from the north-Western Adriatic Sea--15
      years of studies on cultured species.
AB  - The Northern Adriatic Sea is the area of the Mediterranean Sea where
      eutrophication and episodes related to harmful algae have occurred most
      frequently since the 1970s. In this area, which is highly exploited for mollusk
      farming, the first occurrence of human intoxication due to shellfish consumption
      occurred in 1989, nearly 10 years later than other countries in Europe and
      worldwide that had faced similar problems. Until 1997, Adriatic mollusks had been
      found to be contaminated mostly by diarrhetic shellfish poisoning toxins (i.e.,
      okadaic acid and dinophysistoxins) that, along with paralytic shellfish poisoning
      toxins (i.e., saxitoxins), constitute the most common marine biotoxins. Only
      once, in 1994, a toxic outbreak was related to the occurrence of paralytic
      shellfish poisoning toxins in the Adriatic coastal waters. Moreover, in the past
      15 years, the Adriatic Sea has been characterized by the presence of toxic or
      potentially toxic algae, not highly widespread outside Europe, such as species
      producing yessotoxins (i.e., Protoceratium reticulatum, Gonyaulax spinifera and
      Lingulodinium polyedrum), recurrent blooms of the potentially ichthyotoxic
      species Fibrocapsa japonica and, recently, by blooms of palytoxin-like producing
      species of the Ostreopsis genus. This review is aimed at integrating monitoring
      data on toxin spectra and levels in mussels farmed along the coast of the Emilia
      Romagna region with laboratory studies performed on the species involved in the
      production of those toxins; toxicity studies on toxic or potentially toxic
      species that have recently appeared in this area are also reviewed. Overall,
      reviewed data are related to: (i) the yessotoxins producing species P.
      reticulatum, G. spinifera and L. polyedrum, highlighting genetic and toxic
      characteristics; (ii) Adriatic strains of Alexandrium minutum, Alexandrium
      ostenfeldii and Prorocentrum lima whose toxic profiles are compared with those of
      strains of different geographic origins; (iii) F. japonica and Ostreopsis cf.
      ovata toxicity. Moreover, new data concerning domoic acid production by a Pseudo
      nitzschia multistriata strain, toxicity investigations on a Prorocentrum cf.
      levis, and on presumably ichthyotoxic species, Heterosigma akashiwo and
      Chattonella cf. subsalsa, are also reported.

PMID- 22363229
TI  - Differential expression of the demosponge (Suberites domuncula) carotenoid
      oxygenases in response to light: protection mechanism against the self-produced
      toxic protein (Suberitine).
AB  - The demosponge Suberites domuncula has been described to contain high levels of a
      proteinaceous toxin, Suberitine, that displays haemolytic activityIn the present
      study this 7-8 kDa polypeptide has been isolated and was shown to exhibit also
      cytotoxic effects on cells of the same species. Addition of retinal, a recently
      identified metabolite of beta-carotene that is abundantly present in S. domuncula
      was found to reduce both the haemolytic and the cell toxic activity of Suberitine
      at a molar ratio of 1:1. Spectroscopic analyses revealed that the interaction
      between beta-carotene and Suberitine can be ascribed to a reversible energy
      transfer reaction. The enzyme that synthesises retinal in the sponge system is
      the beta,beta-carotene-15,15'-dioxygenase [carotene dioxygenase]. In order to
      clarify if this enzyme is the only beta-carotene-metabolizing enzyme a further
      oxygenase had been identified and cloned, the (related) carotenoid oxygenase. In
      contrast to the dioxygenase, the carotenoid oxygenase could not degrade beta
      carotene or lycopene in Escherichia coli strains that produced these two
      carotenoids; therefore it had been termed related-carotenoid oxygenase. Exposure
      of primmorphs to light of different wavelengths from the visible spectrum
      resulted after 3 days in a strong upregulation of the dioxygenase in those 3D
      cell aggregates that had been incubated with beta-carotene. The strongest effect
      is seen with blue light at a maximum around 490 nm. It is concluded that the
      toxin Suberitine is non-covalently modified by retinal, the cleavage product from
      beta-carotene via the enzyme carotene dioxygenase, a light inducible oxygenase.
      Hence, this study highlights that in S. domuncula the bioactive metabolite,
      retinal, has the property to detoxify its homologous toxin.

PMID- 22363230
TI  - Aurantoside K, a new antifungal tetramic acid glycoside from a Fijian marine
      sponge of the genus Melophlus.
AB  - A new tetramic acid glycoside, aurantoside K, was isolated from a marine sponge
      belonging to the genus Melophlus. The structure of the compound was elucidated on
      the basis of spectroscopic analysis (1H NMR, 1H-1H COSY, HSQC, and HMBC, as well
      as high-resolution ESILCMS). Aurantoside K did not show any significant activity
      in antimalarial, antibacterial, or HCT-116 cytotoxicity assays, but exhibited a
      wide spectrum of antifungal activity against wild type Candida albicans,
      amphotericin-resistant C. albicans, Cryptococcus neoformans, Aspergillus niger,
      Penicillium sp., Rhizopus sporangia and Sordaria sp.

PMID- 22363231
TI  - Bioactive hydroperoxyl cembranoids from the Red Sea soft coral Sarcophyton
      glaucum.
AB  - A chemical investigation of an ethyl acetate extract of the Red Sea soft coral
      Sarcophyton glaucum has led to the isolation of two peroxide diterpenes, 11(S)
      hydroperoxylsarcoph-12(20)-ene (1), and 12(S)-hydroperoxylsarcoph-10-ene (2), as
      well as 8-epi-sarcophinone (3). In addition to these three new compounds, two
      known structures were identified including: ent-sarcophine (4) and sarcophine
      (5). Structures were elucidated by spectroscopic analysis, with the relative
      configuration of 1 and 2 confirmed by X-ray diffraction. Isolated compounds were
      found to be inhibitors of cytochrome P450 1A activity as well as inducers of
      glutathione S-transferases (GST), quinone reductase (QR), and epoxide hydrolase
      (mEH) establishing chemo-preventive and tumor anti-initiating activity for these
      characterized metabolites.

PMID- 22363232
TI  - The alkaloid Ageladine A, originally isolated from marine sponges, used for pH
      sensitive imaging of transparent marine animals.
AB  - The brominated pyrrole-imidazole Ageladine A was used for live imaging of the
      jellyfish (jellies) Nausithoe werneri, the sea anemone Metridium senile and the
      flatworm Macrostomum lignano. The fluorescence properties of Ageladine A allow
      for estimation of pH values in tissue and organs in living animals. The results
      showed that Nausithoe werneri had the most acidic areas in the tentacles and
      close to the mouth (pH 4-6.5), Metridium senile harbours aggregates of high
      acidity in the tentacles (pH 5) and in Macrostomum lignano, the rhabdoids, the
      gonads and areas close to the mouth were the most acidic with values down to pH
      5.

PMID- 22363233
TI  - Antibacterial bisabolane-type sesquiterpenoids from the sponge-derived fungus
      Aspergillus sp.
AB  - Four new bisabolane-type sesquiterpenoids, aspergiterpenoid A (1), (-)-sydonol
      (2), (-)-sydonic acid (3), and (-)-5-(hydroxymethyl)-2-(2',6',6'
      trimethyltetrahydro-2H- pyran-2-yl)phenol (4) together with one known fungal
      metabolite (5) were isolated from the fermentation broth of a marine-derived
      fungus Aspergillus sp., which was isolated from the sponge Xestospongia
      testudinaria collected from the South China Sea. Four of them (1-4) are optically
      active compounds. Their structures and absolute configurations were elucidated by
      using NMR spectroscopic techniques and mass spectrometric analysis, and by
      comparing their optical rotations with those related known analogues. Compounds 1
      5 showed selective antibacterial activity against eight bacterial strains with
      the MIC (minimum inhibiting concentrations) values between 1.25 and 20.0 uM. The
      cytotoxic, antifouling, and acetylcholinesterase inhibitory activities of these
      compounds were also examined.

PMID- 22363235
TI  - Chitosan, the marine functional food, is a potent adsorbent of humic acid.
AB  - Chitosan is prepared by the deacetylation of chitin, the second-most abundant
      biopolymer in nature, and has applicability in the removal of dyes, heavy metals
      and radioactive waste for pollution control. In weight-reduction remedies,
      chitosan is used to form hydrogels with lipids and to depress the intestinal
      absorption of lipids. In this study, an experimental method was implemented to
      simulate the effect of chitosan on the adsorption of humic acid in the
      gastrointestinal tract. The adsorption capacity of chitosan was measured by its
      adsorption isotherm and analyzed using the Langmuir equation. The results showed
      that 3.3 grams of humic acid was absorbed by 1 gram of chitosan. The adsorption
      capacity of chitosan was much greater than that of chitin, diethylaminoethyl
      cellulose or activated charcoal. Cellulose and carboxymethyl-cellulose, a
      cellulose derivative with a negative charge, could not adsorb humic acid in the
      gastrointestinal tract. This result suggests that chitosan entraps humic acid
      because of its positive charge.

PMID- 22363234
TI  - Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple
      drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)
      mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells.
AB  - Pregnane X receptor (PXR) has been reported to regulate the expression of drug
      metabolizing enzymes, such as the cytochrome P450 3A (CYP3A) family and
      transporters, such as multiple drug resistance 1 (MDR1). Fucoxanthin, the major
      carotenoid in brown sea algae, is a putative chemopreventive agent. In this
      study, we determined whether fucoxanthin could overcome drug resistance through
      attenuation of rifampin-induced CYP3A4 and MDR1 gene expression by PXR-mediated
      pathways in HepG2 hepatoma cells. We found that fucoxanthin (1-10 MUM)
      significantly attenuated rifampin (20 MUM)-induced CYP3A4, MDR1 mRNA and CYP3A4
      protein expression at 24 h of incubation. Mechanistically, fucoxanthin strongly
      attenuated the PXR-mediated CYP3A4 promoter activity in HepG2 cells. In addition,
      fucoxanthin attenuated constitutive androstane receptor (CAR)- and rPXR-mediated
      CYP3A4 promoter activity in this cell line. Using the mammalian two-hybrid assay,
      we found that fucoxanthin significantly decreased the interaction between PXR and
      SRC-1, a PXR co-activator. Thus, fucoxanthin can decrease rifampin-induced CYP3A4
      and MDR1 expression through attenuation of PXR-mediated CYP3A4 promoter
      activation and interaction between PXR and co-activator. These findings could
      lead to potentially important new therapeutic and dietary approaches to reduce
      the frequency of adverse drug reactions.

PMID- 22363236
TI  - Relevant spatial scales of chemical variation in Aplysina aerophoba.
AB  - Understanding the scale at which natural products vary the most is critical
      because it sheds light on the type of factors that regulate their production. The
      sponge Aplysina aerophoba is a common Mediterranean sponge inhabiting shallow
      waters in the Mediterranean and its area of influence in Atlantic Ocean. This
      species contains large concentrations of brominated alkaloids (BAs) that play a
      number of ecological roles in nature. Our research investigates the ecological
      variation in BAs of A. aerophoba from a scale of hundred of meters to thousand
      kilometers. We used a nested design to sample sponges from two geographically
      distinct regions (Canary Islands and Mediterranean, over 2500 km), with two zones
      within each region (less than 50 km), two locations within each zone (less than 5
      km), and two sites within each location (less than 500 m). We used high
      performance liquid chromatography to quantify multiple BAs and a
      spectrophotometer to quantify chlorophyll a (Chl a). Our results show a striking
      degree of variation in both natural products and Chl a content. Significant
      variation in Chl a content occurred at the largest and smallest geographic
      scales. The variation patterns of BAs also occurred at the largest and smallest
      scales, but varied depending on which BA was analyzed. Concentrations of Chl a
      and isofistularin-3 were negatively correlated, suggesting that symbionts may
      impact the concentration of some of these compounds. Our results underline the
      complex control of the production of secondary metabolites, with factors acting
      at both small and large geographic scales affecting the production of multiple
      secondary metabolites.

PMID- 22363237
TI  - Seaweed polysaccharides and derived oligosaccharides stimulate defense responses
      and protection against pathogens in plants.
AB  - Plants interact with the environment by sensing "non-self" molecules called
      elicitors derived from pathogens or other sources. These molecules bind to
      specific receptors located in the plasma membrane and trigger defense responses
      leading to protection against pathogens. In particular, it has been shown that
      cell wall and storage polysaccharides from green, brown and red seaweeds (marine
      macroalgae) corresponding to ulvans, alginates, fucans, laminarin and
      carrageenans can trigger defense responses in plants enhancing protection against
      pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed
      polysaccharides also induce protection against viral, fungal and bacterial
      infections in plants. In particular, most seaweed polysaccharides and derived
      oligosaccharides trigger an initial oxidative burst at local level and the
      activation of salicylic (SA), jasmonic acid (JA) and/or ethylene signaling
      pathways at systemic level. The activation of these signaling pathways leads to
      an increased expression of genes encoding: (i) Pathogenesis-Related (PR) proteins
      with antifungal and antibacterial activities; (ii) defense enzymes such as
      pheylalanine ammonia lyase (PAL) and lipoxygenase (LOX) which determine
      accumulation of phenylpropanoid compounds (PPCs) and oxylipins with antiviral,
      antifugal and antibacterial activities and iii) enzymes involved in synthesis of
      terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus,
      seaweed polysaccharides and their derived oligosaccharides induced the
      accumulation of proteins and compounds with antimicrobial activities that
      determine, at least in part, the enhanced protection against pathogens in plants.

PMID- 22363238
TI  - Tetrahydrofuran cembranoids from the cultured soft coral Lobophytum crassum.
AB  - Three new cembranoids, culobophylins A-C (1-3), along with two known compounds (4
      and 5) were isolated from the cultured soft coral Lobophytum crassum. The
      structures of these compounds were elucidated on the basis of their spectroscopic
      data and comparison of the NMR data with those of known analogues. Among these
      metabolites, 2 is rarely found in cembranoids possessing an isopropyl moiety with
      an epoxide group. Compound 1 exhibited significant cytotoxic activity against
      HL60 and DLD-1 cancer cell lines.

PMID- 22363239
TI  - Inhibition of virulence gene expression in Staphylococcus aureus by novel
      depsipeptides from a marine photobacterium.
AB  - During a global research expedition, more than five hundred marine bacterial
      strains capable of inhibiting the growth of pathogenic bacteria were collected.
      The purpose of the present study was to determine if these marine bacteria are
      also a source of compounds that interfere with the agr quorum sensing system that
      controls virulence gene expression in Staphylococcus aureus. Using a gene
      reporter fusion bioassay, we recorded agr interference as enhanced expression of
      spa, encoding Protein A, concomitantly with reduced expression of hla, encoding
      alpha-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A
      marine Photobacterium produced compounds interfering with agr in S. aureus strain
      8325-4, and bioassay-guided fractionation of crude extracts led to the isolation
      of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot
      analysis confirmed the agr interfering activity of pure solonamides in both S.
      aureus strain 8325-4 and the highly virulent, community-acquired strain USA300
      (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr
      system by a marine bacterium.

PMID- 22363240
TI  - A kinetic study of accumulation and elimination of microcystin-LR in yellow perch
      (Perca flavescens) tissue and implications for human fish consumption.
AB  - Fish consumption is a potential route of human exposure to the hepatotoxic
      microcystins, especially in lakes and reservoirs that routinely experience
      significant toxic Microcystis blooms. Understanding the rates of uptake and
      elimination for microcystins as well as the transfer efficiency into tissues of
      consumers are important for determining the potential for microcystins to be
      transferred up the food web and for predicting potential human health impacts.
      The main objective of this work was to conduct laboratory experiments to
      investigate the kinetics of toxin accumulation in fish tissue. An oral route of
      exposure was employed in this study, in which juvenile yellow perch (Perca
      flavescens) were given a single oral dose of 5 or 20 MUg of microcystin-LR (MC
      LR) via food and accumulation in the muscle, liver, and tank water were measured
      over 24 h. Peak concentrations of the water soluble fraction of microcystin were
      generally observed 8-10 h after dosing in the liver and after 12-16 h in the
      muscle, with a rapid decline in both tissues by 24 h. Up to 99% of the total
      recoverable (i.e., unbound) microcystin was measured in the tank water by 16 h
      after exposure. The relatively rapid uptake and elimination of the unbound
      fraction of microcystin in the liver and muscle of juvenile yellow perch within
      24 h of exposure indicates that fish consumption may not be a major route of
      human exposure to microcystin, particularly in the Great Lakes.

PMID- 22363242
TI  - Fucose-containing sulfated polysaccharides from brown seaweeds inhibit
      proliferation of melanoma cells and induce apoptosis by activation of caspase-3
      in vitro.
AB  - Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds,
      especially brown macro-algae, are known to possess essential bioactive
      properties, notably growth inhibitory effects on tumor cells. In this work, we
      conducted a series of in vitro studies to examine the influence of FCSPs products
      from Sargassumhenslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES),
      respectively, on proliferation of melanoma B16 cells and to investigate the
      underlying apoptosis promoting mechanisms. Cell viability analysis showed that
      both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the
      melanoma cells in a dose-response fashion, with FSAR being more potent at lower
      dosages, and FVES being relatively more anti-proliferative than FSAR at higher
      dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells
      exposed to the FCSPs products confirmed that both FSAR and FVES induced
      apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane
      asymmetry and translocation of the cell membrane phospholipids and was
      accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to
      be attributable to distinct structural features of the FCSPs, particularly the
      presence of sulfated galactofucans (notably in S.henslowianum) and sulfated
      fucans (notably in F. vesiculosus). This study thus indicates that unfractionated
      FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis
      through cascades of reactions that involve activation of caspase-3.

PMID- 22363241
TI  - Marine polysaccharides in microencapsulation and application to aquaculture:
      "from sea to sea".
AB  - This review's main objective is to discuss some physico-chemical features of
      polysaccharides as intrinsic determinants for the supramolecular structures that
      can efficiently provide encapsulation of drugs and other biological entities.
      Thus, the general characteristics of some basic polysaccharides are outlined in
      terms of their conformational, dynamic and thermodynamic properties. The analysis
      of some polysaccharide gelling properties is also provided, including the
      peculiarity of the charged polysaccharides. Then, the way the basic physical
      chemistry of polymer self-assembly is made in practice through the laboratory
      methods is highlighted. A description of the several literature procedures used
      to influence molecular interactions into the macroscopic goal of the
      encapsulation is given with an attempt at classification. Finally, a practical
      case study of specific interest, the use of marine polysaccharide matrices for
      encapsulation of vaccines in aquaculture, is reported.

PMID- 22363243
TI  - An investigation into the cytotoxic effects of 13-acetoxysarcocrassolide from the
      soft coral Sarcophyton crassocaule on bladder cancer cells.
AB  - Active compounds from natural products have been widely studied. The anti-tumor
      effects of 13-acetoxysarcocrassolide isolated from Formosan soft coral
      Sarcophyton crassocaule on bladder cancer cells were examined in this study. An
      MTT assay showed that 13-acetoxysarcocrassolide was cytotoxic to bladder female
      transitional cancer (BFTC) cells. We determined that the BFTC cells underwent
      cell death through apoptosis by flow cytometry. Due to the highly-migratory
      nature of the BFTC cells, the ability of 13-acetoxysarcocrassolide to stop their
      migration was assessed by a wound healing assay. To determine which proteins were
      affected in the BFTC cells upon treatment, a comparative proteomic analysis was
      performed. By LC-MS/MS analysis, we identified that 19 proteins were up-regulated
      and eight were down-regulated. Seven of the proteins were confirmed by western
      blotting analysis. This study reveals clues to the potential mechanism of the
      cytotoxic effects of 13-acetoxysarcocrassolide on BFTC cells. Moreover, it
      suggests that PPT1 and hnRNP F could be new biomarkers for bladder cancer. The
      results of this study are also helpful for the diagnosis, progression monitoring
      and therapeutic strategies of transitional cell tumors.

PMID- 22363246
TI  - Cembranoids from the Dongsha Atoll soft coral Lobophytum crassum.
AB  - Chemical investigation of the Dongsha Atoll soft coral Lobophytum crassum has
      afforded four new cembranoids, crassumols A-C (1-3) and 13-acetoxysarcophytoxide
      (4). The structures of these isolated compounds were elucidated by extensive NMR
      and HRESIMS experiments. The cytotoxicity and anti-HCMV (Human cytomegalovirus)
      activities of 1-4 were evaluated in vitro. Compound 4 exhibited cytotoxicity
      against A-549 (human lung carcinoma) cell line with an ED(50) of 3.6 MUg/mL.

PMID- 22363244
TI  - Natural products from the Lithistida: a review of the literature since 2000.
AB  - Lithistid sponges are known to produce a diverse array of compounds ranging from
      polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and
      sterols. A majority of these structurally complex compounds have very potent and
      interesting biological activities. It has been a decade since a thorough review
      has been published that summarizes the literature on the natural products
      reported from this amazing sponge order. This review provides an update on the
      current taxonomic classification of the Lithistida, describes structures and
      biological activities of 131 new natural products, and discusses highlights from
      the total syntheses of 16 compounds from marine sponges of the Order Lithistida
      providing a compilation of the literature since the last review published in
      2002.

PMID- 22363245
TI  - Tetrodotoxin as a tool to elucidate sensory transduction mechanisms: the case for
      the arterial chemoreceptors of the carotid body.
AB  - Carotid bodies (CBs) are secondary sensory receptors in which the sensing
      elements, chemoreceptor cells, are activated by decreases in arterial PO(2)
      (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and
      glomus cells) increase their rate of release of neurotransmitters that drive the
      sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem
      where reflex responses are coordinated. When challenged with hypoxic hypoxia, the
      physiopathologically most relevant stimulus to the CBs, they are activated and
      initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute
      volume ventilation promotes CO(2) removal from alveoli and a decrease in alveolar
      PCO(2) ensues. Reduced alveolar PCO(2) makes possible alveolar and arterial PO(2)
      to increase minimizing the intensity of hypoxia. The ventilatory effect, in
      conjunction the cardiocirculatory components of the CB chemoreflex, tend to
      maintain an adequate supply of oxygen to the tissues. The CB has been the focus
      of attention since the discovery of its nature as a sensory organ by de Castro
      (1928) and the discovery of its function as the origin of ventilatory reflexes by
      Heymans' group (1930). A great deal of effort has been focused on the study of
      the mechanisms involved in O(2) detection. This review is devoted to this topic,
      mechanisms of oxygen sensing. Starting from a summary of the main theories
      evolving through the years, we will emphasize the nature and significance of the
      findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of
      current models of O(2)-sensing.

PMID- 22363247
TI  - Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia.
AB  - Currently available local anesthetics have analgesic durations in humans
      generally less than 12 hours. Prolonged-duration local anesthetics will be useful
      for postoperative analgesia. Previous studies showed that in rats, combinations
      of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic
      block durations. In those studies, epinephrine combined with TTX prolonged blocks
      more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin,
      is in phase III clinical trials as an injectable systemic analgesic for chronic
      cancer pain. Here, we examine dose-duration relationships and sciatic nerve
      histology following local nerve blocks with combinations of Tectin with
      bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 ug/mL
      (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague
      Dawley rats, and intensity and duration of sensory blockade was tested blindly
      with different Tectin-bupivacaine-epinephrine combinations. Between-group
      comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were
      examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with
      Tectin 10 uM and epinephrine 5 ug/mL were prolonged by roughly 3-fold compared to
      blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with
      epinephrine 5 ug/mL (P < 0.001). Nerve histology was benign for all groups.
      Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 ug/mL appear
      promising for prolonged duration of local anesthesia.

PMID- 22363249
TI  - Natural product chemistry of gorgonian corals of genus Junceella--part II.
AB  - The structures, names, bioactivities, and references of 81 new secondary
      metabolites obtained from gorgonian corals belonging to the genus Junceella are
      described in this review. All compounds mentioned in this review were obtained
      from sea whip gorgonian corals Junceella fragilis and Junceella juncea, collected
      from the tropical and subtropical Indo-Pacific Ocean.

PMID- 22363248
TI  - Cyanotoxins: bioaccumulation and effects on aquatic animals.
AB  - Cyanobacteria are photosynthetic prokaryotes with wide geographic distribution
      that can produce secondary metabolites named cyanotoxins. These toxins can be
      classified into three main types according to their mechanism of action in
      vertebrates: hepatotoxins, dermatotoxins and neurotoxins. Many studies on the
      effects of cyanobacteria and their toxins over a wide range of aquatic organisms,
      including invertebrates and vertebrates, have reported acute effects (e.g.,
      reduction in survivorship, feeding inhibition, paralysis), chronic effects (e.g.,
      reduction in growth and fecundity), biochemical alterations (e.g., activity of
      phosphatases, GST, AChE, proteases), and behavioral alterations. Research has
      also focused on the potential for bioaccumulation and transferring of these
      toxins through the food chain. Although the herbivorous zooplankton is
      hypothesized as the main target of cyanotoxins, there is not unquestionable
      evidence of the deleterious effects of cyanobacteria and their toxins on these
      organisms. Also, the low toxin burden in secondary consumers points towards
      biodilution of microcystins in the food web as the predominant process. In this
      broad review we discuss important issues on bioaccumulation and the effects of
      cyanotoxins, with emphasis on microcystins, as well as drawbacks and future needs
      in this field of research.

PMID- 22363250
TI  - Inhibitory effects of Ecklonia cava extract on high glucose-induced hepatic
      stellate cell activation.
AB  - Nonalcoholic steatohepatitis (NASH) is a disease closely associated with obesity
      and diabetes. A prevalence of type 2 diabetes and a high body mass index in
      cryptogenic cirrhosis may imply that obesity leads to cirrhosis. Here, we
      examined the effects of an extract of Ecklonia cava, a brown algae, on the
      activation of high glucose-induced hepatic stellate cells (HSCs), key players in
      hepatic fibrosis. Isolated HSCs were incubated with or without a high glucose
      concentration. Ecklonia cava extract (ECE) was added to the culture
      simultaneously with the high glucose. Treatment with high glucose stimulated
      expression of type I collagen and alpha-smooth muscle actin, which are markers of
      activation in HSCs, in a dose-dependent manner. The activation of high glucose
      treated HSCs was suppressed by the ECE. An increase in the formation of
      intracellular reactive oxygen species (ROS) and a decrease in intracellular
      glutathione levels were observed soon after treatment with high glucose, and
      these changes were suppressed by the simultaneous addition of ECE. High glucose
      levels stimulated the secretion of bioactive transforming growth factor-beta (TGF
      beta) from the cells, and the stimulation was also suppressed by treating the
      HSCs with ECE. These results suggest that the suppression of high glucose-induced
      HSC activation by ECE is mediated through the inhibition of ROS and/or GSH and
      the downregulation of TGF-beta secretion. ECE is useful for preventing the
      development of diabetic liver fibrosis.

PMID- 22363251
TI  - Aurantoside J: a new tetramic acid glycoside from Theonella swinhoei. Insights
      into the antifungal potential of aurantosides.
AB  - The chemical investigation of an Indonesian specimen of Theonella swinhoei
      afforded four aurantosides, one of which, aurantoside J (5), is a new compound.
      The structure of this metabolite, exhibiting the unprecedented N-alpha-glycosidic
      linkage between the pentose and the tetramate units, has been determined through
      detailed spectroscopic analysis. The four obtained aurantosides have been tested
      against five fungal strains (four Candida and one Fusarium) responsible of
      invasive infections in immuno-compromised patients. The non-cytotoxic aurantoside
      I (4) was the single compound to show an excellent potency against all the tested
      strains, thus providing valuable insights about the antifungal potential of this
      class of compounds and the structure-activity relationships.

PMID- 22363252
TI  - Impact of size and delay on neural activity in the rat limbic corticostriatal
      system.
AB  - A number of factors influence an animal's economic decisions. Two most commonly
      studied are the magnitude of and delay to reward. To investigate how these
      factors are represented in the firing rates of single neurons, we devised a
      behavioral task that independently manipulated the expected delay to and size of
      reward. Rats perceived the differently delayed and sized rewards as having
      different values and were more motivated under short delay and big-reward
      conditions than under long delay and small reward conditions as measured by
      percent choice, accuracy, and reaction time. Since the creation of this task, we
      have recorded from several different brain areas including, orbitofrontal cortex,
      striatum, amygdala, substantia nigra pars reticulata, and midbrain dopamine
      neurons. Here, we review and compare those data with a substantial focus on those
      areas that have been shown to be critical for performance on classic time
      discounting procedures and provide a potential mechanism by which they might
      interact when animals are deciding between differently delayed rewards. We found
      that most brain areas in the cortico-limbic circuit encode both the magnitude and
      delay to reward delivery in one form or another, but only a few encode them
      together at the single neuron level.

PMID- 22363254
TI  - Experience and abstract reasoning in learning backward induction.
AB  - Backward induction is a benchmark of game theoretic rationality, yet surprisingly
      little is known as to how humans discover and initially learn to apply this
      abstract solution concept in experimental settings. We use behavioral and
      functional magnetic resonance imaging (fMRI) data to study the way in which
      subjects playing in a sequential game of perfect information learn the optimal
      backward induction strategy for the game. Experimental data from our two studies
      support two main findings: First, subjects converge to a common process of
      recursive inference similar to the backward induction procedure for solving the
      game. The process is recursive because earlier insights and conclusions are used
      as inputs in later steps of the inference. This process is matched by a similar
      pattern in brain activation, which also proceeds backward, following the
      prediction error: brain activity initially codes the responses to losses in final
      positions; in later trials this activity shifts to the starting position. Second,
      the learning process is not exclusively cognitive, but instead combines
      experience-based learning and abstract reasoning. Critical experiences leading to
      the adoption of an improved solution strategy appear to be stimulated by brain
      activity in the reward system. This indicates that the negative affect induced by
      initial failures facilitates the switch to a different method of solving the
      problem. Abstract reasoning is combined with this response, and is expressed by
      activation in the ventrolateral prefrontal cortex. Differences in brain
      activation match differences in performance between subjects who show different
      learning speeds.

PMID- 22363253
TI  - Scarce means with alternative uses: robbins' definition of economics and its
      extension to the behavioral and neurobiological study of animal decision making.
AB  - Almost 80 years ago, Lionel Robbins proposed a highly influential definition of
      the subject matter of economics: the allocation of scarce means that have
      alternative ends. Robbins confined his definition to human behavior, and he
      strove to separate economics from the natural sciences in general and from
      psychology in particular. Nonetheless, I extend his definition to the behavior of
      non-human animals, rooting my account in psychological processes and their neural
      underpinnings. Some historical developments are reviewed that render such a view
      more plausible today than would have been the case in Robbins' time. To
      illustrate a neuroeconomic perspective on decision making in non-human animals, I
      discuss research on the rewarding effect of electrical brain stimulation. Central
      to this discussion is an empirically based, functional/computational model of how
      the subjective intensity of the electrical reward is computed and combined with
      subjective costs so as to determine the allocation of time to the pursuit of
      reward. Some successes achieved by applying the model are discussed, along with
      limitations, and evidence is presented regarding the roles played by several
      different neural populations in processes posited by the model. I present a
      rationale for marshaling convergent experimental methods to ground psychological
      and computational processes in the activity of identified neural populations, and
      I discuss the strengths, weaknesses, and complementarity of the individual
      approaches. I then sketch some recent developments that hold great promise for
      advancing our understanding of structure-function relationships in neuroscience
      in general and in the neuroeconomic study of decision making in particular.

PMID- 22363257
TI  - Fibroblast growth factor 22 contributes to the development of retinal nerve
      terminals in the dorsal lateral geniculate nucleus.
AB  - At least three forms of signaling between pre- and postsynaptic partners are
      necessary during synapse formation. First, "targeting" signals instruct
      presynaptic axons to recognize and adhere to the correct portion of a
      postsynaptic target cell. Second, trans-synaptic "organizing" signals induce
      differentiation in their synaptic partner so that each side of the synapse is
      specialized for synaptic transmission. Finally, in many regions of the nervous
      system an excess of synapses are initially formed, therefore "refinement" signals
      must either stabilize or destabilize the synapse to reinforce or eliminate
      connections, respectively. Because of both their importance in processing visual
      information and their accessibility, retinogeniculate synapses have served as a
      model for studying synaptic development. Molecular signals that drive
      retinogeniculate "targeting" and "refinement" have been identified, however,
      little is known about what "organizing" cues are necessary for the
      differentiation of retinal axons into presynaptic terminals. To identify such
      "organizing" cues, we used microarray analysis to assess whether any target
      derived "synaptic organizers" were enriched in the mouse dorsal lateral
      geniculate nucleus (dLGN) during retinogeniculate synapse formation. One
      candidate "organizing" molecule enriched in perinatal dLGN was FGF22, a secreted
      cue that induces the formation of excitatory nerve terminals in muscle,
      hippocampus, and cerebellum. In FGF22 knockout mice, the development of retinal
      terminals in dLGN was impaired. Thus, FGF22 is an important "organizing" cue for
      the timely development of retinogeniculate synapses.

PMID- 22363255
TI  - New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs.
AB  - Adult neurogenesis generates functional neurons from neural stem cells present in
      specific brain regions. It is largely confined to two main regions: the
      subventricular zone of the lateral ventricle, and the subgranular zone of the
      dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus
      and particularly the DG is impaired. For instance, adult neurogenesis is
      decreased with aging, in both proliferating and differentiation of newborn cells,
      while in parallel an age-associated decline in cognitive performance is often
      seen. Surprisingly, the synaptogenic potential of adult-born neurons is only
      marginally influenced by aging. Therefore, although proliferation,
      differentiation, and synaptogenesis of adult-born new neurons in the DG are
      closely related to each other, they are differentially affected by aging. In this
      review we discuss the crucial roles of a novel class of recently discovered
      modulators of gene expression, the small non-coding RNAs, in the regulation of
      adult neurogenesis. Multiple small non-coding RNAs are differentially expressed
      in the hippocampus. In particular a subgroup of the small non-coding RNAs, the
      microRNAs, fine-tune the progression of adult neurogenesis. This makes small non
      coding RNAs appealing candidates to orchestrate the functional alterations in
      adult neurogenesis and cognition associated with aging. Finally, we summarize
      observations that link changes in circulating levels of steroid hormones with
      alterations in adult neurogenesis, cognitive decline, and vulnerability to
      psychopathology in advanced age, and discuss a potential interplay between
      steroid hormone receptors and microRNAs in cognitive decline in aging
      individuals.

PMID- 22363258
TI  - GSK3 as a Sensor Determining Cell Fate in the Brain.
AB  - Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that
      controls many neuronal functions, including neurite outgrowth, synapse formation,
      neurotransmission, and neurogenesis. It mediates these functions by
      phosphorylating a wide range of substrates involved in gene transcription,
      metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane
      dynamics, and trafficking, amongst others. This complicated list of diverse
      substrates generally follow a more simple pattern: substrates negatively
      regulated by GSK3-mediated phosphorylation favor a proliferative/survival state,
      while substrates positively regulated by GSK3 favor a more
      differentiated/functional state. Accordingly, GSK3 activity is higher in
      differentiated cells than undifferentiated cells and physiological (Wnt, growth
      factors) and pharmacological inhibitors of GSK3 promote the proliferative
      capacity of embryonic stem cells. In the brain, the level of GSK3 activity
      influences neural progenitor cell proliferation/differentiation in
      neuroplasticity and repair, as well as efficient neurotransmission in
      differentiated adult neurons. While defects in GSK3 activity are unlikely to be
      the primary cause of neurodegenerative diseases, therapeutic regulation of its
      activity to promote a proliferative/survival versus differentiated/mature
      functional environment in the brain could be a powerful strategy for treatment of
      neurodegenerative and other mental disorders.

PMID- 22363259
TI  - Expression of the Wnt signaling system in central nervous system axon guidance
      and regeneration.
AB  - Wnt signaling is essential for axon wiring throughout the development of the
      nervous system in vertebrates and invertebrates. In rodents, Wnts are expressed
      in gradients that span the entire anterior-posterior (A-P) axis in the spinal
      cord and the medial-lateral axis in the superior colliculus. In the brainstem,
      Wnts are expressed in more complex gradients along the A-P axis. These gradients
      provide directional information for axon pathfinding and positional information
      for topographic mapping and are detected by cell polarity signaling pathways in
      the growth cone. The gradient expression of Wnts and the coordinated expression
      of Wnt signaling systems are regulated by mechanisms which are currently unknown.
      Injury to the adult spinal cord results in the re-induction of Wnts in multiple
      cell types around the lesion site and their signaling system in injured axons.
      The re-induced Wnts form gradients around the lesion site, with the lesion site
      being the peak. The re-inducedWnts may be responsible for the well-known
      retraction of descending motor axons through the receptor Ryk (related receptor
      tyrosine kinases). Wnt signaling is an appealing new therapeutic target for CNS
      repair. The mechanisms regulating the re-induction are unknown but will be
      informative for therapeutic design.

PMID- 22363256
TI  - Sexual differentiation of the rodent brain: dogma and beyond.
AB  - Steroid hormones of gonadal origin act on the neonatal brain to produce sex
      differences that underlie adult reproductive physiology and behavior. Neuronal
      sex differences occur on a variety of levels, including differences in regional
      volume and/or cell number, morphology, physiology, molecular signaling, and gene
      expression. In the rodent, many of these sex differences are determined by
      steroid hormones, particularly estradiol, and are established by diverse
      downstream effects. One brain region that is potently organized by estradiol is
      the preoptic area (POA), a region critically involved in many behaviors that show
      sex differences, including copulatory and maternal behaviors. This review focuses
      on the POA as a case study exemplifying the depth and breadth of our knowledge as
      well as the gaps in understanding the mechanisms through which gonadal hormones
      produce lasting neural and behavioral sex differences. In the POA, multiple cell
      types, including neurons, astrocytes, and microglia are masculinized by
      estradiol. Multiple downstream molecular mediators are involved, including
      prostaglandins, various glutamate receptors, protein kinase A, and several immune
      signaling molecules. Moreover, emerging evidence indicates epigenetic mechanisms
      maintain sex differences in the POA that are organized perinatally and thereby
      produce permanent behavioral changes. We also review emerging strategies to
      better elucidate the mechanisms through which genetics and epigenetics contribute
      to brain and behavioral sex differences.

PMID- 22363260
TI  - Role of transcription factors in peripheral nerve regeneration.
AB  - Following axotomy, the activation of multiple intracellular signaling cascades
      causes the expression of a cocktail of regeneration-associated transcription
      factors which interact with each other to determine the fate of the injured
      neurons. The nerve injury response is channeled through manifold and parallel
      pathways, integrating diverse inputs, and controlling a complex transcriptional
      output. Transcription factors form a vital link in the chain of regeneration,
      converting injury-induced stress signals into downstream protein expression via
      gene regulation. They can regulate the intrinsic ability of axons to grow, by
      controlling expression of whole cassettes of gene targets. In this review, we
      have investigated the functional roles of a number of different transcription
      factors - c-Jun, activating transcription factor 3, cAMP response element binding
      protein, signal transducer, and activator of transcription-3, CCAAT/enhancer
      binding proteins beta and delta, Oct-6, Sox11, p53, nuclear factor kappa-light
      chain-enhancer of activated B cell, and ELK3 - in peripheral nerve regeneration.
      Studies involving use of conditional mutants, microarrays, promoter region
      mapping, and different injury paradigms, have enabled us to understand their
      distinct as well as overlapping roles in achieving anatomical and functional
      regeneration after peripheral nerve injury.

PMID- 22363261
TI  - Molecular structure and target recognition of neuronal calcium sensor proteins.
AB  - Neuronal calcium sensor (NCS) proteins, a sub-branch of the EF-hand superfamily,
      are expressed in the brain and retina where they transduce calcium signals and
      are genetically linked to degenerative diseases. The amino acid sequences of NCS
      proteins are highly conserved but their physiological functions are quite
      distinct. Retinal recoverin and guanylate cyclase activating proteins (GCAPs)
      both serve as calcium sensors in retinal rod cells, neuronal frequenin (NCS1)
      modulates synaptic activity and neuronal secretion, K(+) channel interacting
      proteins (KChIPs) regulate ion channels to control neuronal excitability, and
      DREAM (KChIP3) is a transcriptional repressor that regulates neuronal gene
      expression. Here we review the molecular structures of myristoylated forms of
      NCS1, recoverin, and GCAP1 that all look very different, suggesting that the
      sequestered myristoyl group helps to refold these highly homologous proteins into
      very different structures. The molecular structure of NCS target complexes have
      been solved for recoverin bound to rhodopsin kinase (RK), NCS-1 bound to
      phosphatidylinositol 4-kinase, and KChIP1 bound to A-type K(+) channels. We
      propose that N-terminal myristoylation is critical for shaping each NCS family
      member into a different structure, which upon Ca(2+)-induced extrusion of the
      myristoyl group exposes a unique set of previously masked residues that interact
      with a particular physiological target.

PMID- 22363262
TI  - A pivotal role of GSK-3 in synaptic plasticity.
AB  - Glycogen synthase kinase-3 (GSK-3) has many cellular functions. Recent evidence
      suggests that it plays a key role in certain types of synaptic plasticity, in
      particular a form of long-term depression (LTD) that is induced by the synaptic
      activation of N-methyl-D-aspartate receptors (NMDARs). In the present article we
      summarize what is currently known concerning the roles of GSK-3 in synaptic
      plasticity at both glutamatergic and GABAergic synapses. We summarize its role in
      cognition and speculate on how alterations in the synaptic functioning of GSK-3
      may be a major factor in certain neurodegenerative disorders.

PMID- 22363263
TI  - Inhibition of GSK3 by lithium, from single molecules to signaling networks.
AB  - For more than 60 years, the mood stabilizer lithium has been used alone or in
      combination for the treatment of bipolar disorder, schizophrenia, depression, and
      other mental illnesses. Despite this long history, the molecular mechanisms
      trough which lithium regulates behavior are still poorly understood. Among
      several targets, lithium has been shown to directly inhibit glycogen synthase
      kinase 3 alpha and beta (GSK3alpha and GSK3beta). However in vivo, lithium also
      inhibits GSK3 by regulating other mechanisms like the formation of a signaling
      complex comprised of beta-arrestin 2 (betaArr2) and Akt. Here, we provide an
      overview of in vivo evidence supporting a role for inhibition of GSK3 in some
      behavioral effects of lithium. We also explore how regulation of GSK3 by lithium
      within a signaling network involving several molecular targets and cell surface
      receptors [e.g., G protein coupled receptors (GPCRs) and receptor tyrosine
      kinases (RTKs)] may provide cues to its relative pharmacological selectivity and
      its effects on disease mechanisms. A better understanding of these intricate
      actions of lithium at a systems level may allow the rational development of
      better mood stabilizer drugs with enhanced selectivity, efficacy, and lesser side
      effects.

PMID- 22363265
TI  - Association of type I neurons positive for NADPH-diaphorase with blood vessels in
      the adult monkey corpus callosum.
AB  - Sagittal sections through the corpus callosum of adult macaque monkeys (n = 7)
      reveal a subpopulation of neurons positive for NADPH-diaphorase (NADPHd). These
      are sparsely distributed, with 2-12 neurons scored over the anterior two-thirds
      of the callosum (about 14 mm). Neurons are densely labeled, type 1; but on the
      basis of soma and dendritic morphology, these neurons exhibit distinct
      heterogeneity. In one subpopulation, the cell body is narrowly attenuated (7-10
      MUm in width). These have bipolar dendrites, extending 300-800 MUm from the cell
      body. One or both of the dendrites is often closely associated with blood vessels
      and tends to be aligned dorso-ventral, perpendicular to the body of the callosum.
      Another subpopulation of neurons has a larger soma (typically, 15 MUm * 20 MUm)
      and more multipolar dendrites, which are not as obviously associated with blood
      vessels. White matter neurons positive for NADPHd have previously been observed
      as a transient population, most numerous during development, in the human corpus
      callosum, as well as in that of other species. Their persistence in the corpus
      callosum of adult macaques and their close association with blood vessels has not
      previously been reported and is suggestive of roles other than axon guidance.

PMID- 22363264
TI  - Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory
      neurotransmission.
AB  - The K-Cl co-transporter KCC2 plays multiple roles in the physiology of central
      neurons and alterations of its function and/or expression are associated with
      several neurological conditions. By regulating intraneuronal chloride
      homeostasis, KCC2 strongly influences the efficacy and polarity of the chloride
      permeable gamma-aminobutyric acid (GABA) type A and glycine receptor (GlyR)
      mediated synaptic transmission. This appears particularly critical for the
      development of neuronal circuits as well as for the dynamic control of GABA and
      glycine signaling in mature networks. The activity of the transporter is also
      associated with transmembrane water fluxes which compensate solute fluxes
      associated with synaptic activity. Finally, KCC2 interaction with the actin
      cytoskeleton appears critical both for dendritic spine morphogenesis and the
      maintenance of glutamatergic synapses. In light of the pivotal role of KCC2 in
      the maturation and function of central synapses, it is of particular importance
      to understand the cellular and molecular mechanisms underlying its regulation.
      These include development and activity-dependent modifications both at the
      transcriptional and post-translational levels. We emphasize the importance of
      post-translational mechanisms such as phosphorylation and dephosphorylation,
      oligomerization, cell surface stability, clustering and membrane diffusion for
      the rapid and dynamic regulation of KCC2 function.

PMID- 22363267
TI  - Experience-dependent firing rate remapping generates directional selectivity in
      hippocampal place cells.
AB  - When rodents engage in irregular foraging in an open-field environment,
      hippocampal principal cells exhibit place-specific firing that is statistically
      independent of the direction of traverse through the place field. When the path
      is restricted to a track, however, in-field rates differ substantially in
      opposite directions. Frequently, the representations of the track in the two
      directions are essentially orthogonal. We show that this directionally selective
      firing is not hard-wired, but develops through experience-dependent plasticity.
      During the rats' first pass in each direction, place fields were highly
      directionally symmetric, whereas over subsequent laps, the firing rates in the
      two directions gradually but substantially diverged. We conclude that, even on a
      restricted track, place cell firing is initially determined by allocentric
      position, and only later, the within-field firing rates change in response to
      differential sensory information or behavioral cues in the two directions. In
      agreement with previous data, place fields near local cues, such as textures on
      the track, developed less directionality than place fields on a uniform part of
      the track, possibly because the local cues reduced the net difference in sensory
      input at a given point. Directionality also developed in an open environment
      without physical restriction of the animal's path, when rats learned to run along
      a specified path. In this case, directionality developed later than on the
      running track, only after the rats began to run in a stereotyped manner. Although
      the average population firing rates exhibited little if any change over laps in
      either direction, the direction-specific firing rates in a given place field were
      up-or down-regulated with about equal probability and magnitude, which was
      independent in the two directions, suggesting some form of competitive mechanism
      (e.g., LTP/LTD) acting coherently on the set of synapses conveying external
      information to each cell.

PMID- 22363266
TI  - Possible role of acetylcholine in regulating spatial novelty effects on theta
      rhythm and grid cells.
AB  - Existing pharmacological and lesion data indicate that acetylcholine plays an
      important role in memory formation. For example, increased levels of
      acetylcholine in the hippocampal formation are known to be associated with
      successful encoding while disruption of the cholinergic system leads to
      impairments on a range of mnemonic tasks. However, cholinergic signaling from the
      medial septum also plays a central role in generating and pacing theta-band
      oscillations throughout the hippocampal formation. Recent experimental results
      suggest a potential link between these distinct phenomena. Environmental novelty,
      a condition associated with strong cholinergic drive, has been shown to induce an
      expansion in the firing pattern of entorhinal grid cells and a reduction in the
      frequency of theta measured from the LFP. Computational modeling suggests the
      spatial activity of grid cells is produced by interference between neuronal
      oscillators; scale being determined by theta-band oscillations impinging on
      entorhinal stellate cells, the frequency of which is modulated by acetylcholine.
      Here we propose that increased cholinergic signaling in response to environmental
      novelty triggers grid expansion by reducing the frequency of the oscillations.
      Furthermore, we argue that cholinergic induced grid expansion may enhance, or
      even induce, encoding by producing a mismatch between expanded grid cells and
      other spatial inputs to the hippocampus, such as boundary vector cells. Indeed, a
      further source of mismatch is likely to occur between grid cells of different
      native scales which may expand by different relative amounts.

PMID- 22363269
TI  - Differential input of the supplementary motor area to a dedicated temporal
      processing network: functional and clinical implications.

PMID- 22363268
TI  - The genesis of cerebellar GABAergic neurons: fate potential and specification
      mechanisms.
AB  - ALL CEREBELLAR NEURONS DERIVE FROM PROGENITORS THAT PROLIFERATE IN TWO GERMINAL
      NEUROEPITHELIA: the ventricular zone (VZ) generates GABAergic neurons, whereas
      the rhombic lip is the origin of glutamatergic types. Among VZ-derivatives,
      GABAergic projection neurons, and interneurons are generated according to
      distinct strategies. Projection neurons (Purkinje cells and nucleo-olivary
      neurons) are produced at the onset of cerebellar neurogenesis by discrete
      progenitor pools located in distinct VZ microdomains. These cells are specified
      within the VZ and acquire mature phenotypes according to cell-autonomous
      developmental programs. On the other hand, the different categories of inhibitory
      interneurons derive from a single population of Pax-2-positive precursors that
      delaminate into the prospective white matter (PWM), where they continue to divide
      up to postnatal development. Heterotopic/heterochronic transplantation
      experiments indicate that interneuron progenitors maintain full developmental
      potentialities up to the end of cerebellar development and acquire mature
      phenotypes under the influence of environmental cues present in the PWM.
      Furthermore, the final fate choice occurs in postmitotic cells, rather than
      dividing progenitors. Extracerebellar cells grafted to the prospective cerebellar
      white matter are not responsive to local neurogenic cues and fail to adopt clear
      cerebellar identities. Conversely, cerebellar cells grafted to extracerebellar
      regions retain typical phenotypes of cerebellar GABAergic interneurons, but
      acquire type-specific traits under the influence of local cues. These findings
      indicate that interneuron progenitors are multipotent and sensitive to spatio
      temporally patterned environmental signals that regulate the genesis of different
      categories of interneurons, in precise quantities and at defined times and
      places.

PMID- 22363270
TI  - Effects of transplanted GDNF gene modified marrow stromal cells on focal cerebral
      ischemia in rats.
AB  - OBJECTIVE: To evaluate the therapeutic effect of transplanted glial cell derived
      neurotrophic factor (GDNF) modified marrow stromal cells (MSCs) on an
      experimental ischemic brain injury based on the behavioral, morphological, and
      immunohistochemical observations. METHODS: The MSCs from four-week newborn rats
      were cultured in vitro. The cerebral ischemia and reperfusion model was
      established in adult Sprague-Dawley (SD) rats by using the suture method. Three
      days after model establishment, the animals were injected with prepared MSCs via
      their caudal veins. The animals were then divided into a sham-operation group,
      ischemia group, MSCs transplantation group, or GDNF+ MSCs transplantation group
      and were scored for their neurobehavioral manifestations at 3, 14, and 28 days
      after the transplantation was performed. At this time, the survival condition of
      intracerebral transplanted cells was measured by laser confocal microscopy while
      the effect of transplantation on the Generic Digital Beam Former (GDNF)
      expression in the ischemic brain tissue was evaluated. RESULTS: The MSCs cells
      transfected with GDNF gene were characterized by green fluorescence. Three days
      after the transplantation, the animals that underwent the cell transplantation
      showed significantly better behavioral data than the controls. Fourteen days
      after transplantation, the animals transplanted with GDNF gene modified MSCs were
      better than those transplanted with common MSCs. As compared with common MSCs
      transplantation, GDNF+MSCs transplantation was significantly more effective in
      reducing apoptotic cell volume and enhancing Bcl-2 expression, which was
      favorable for the ischemic brain injury. CONCLUSIONS: Transplanted GDNF modified
      MSCs can improve the nervous function and have a protective effect on the
      ischemic brain injury through reducing apoptotic cell volume and enhancing the
      expression of anti-apoptotic gene Bcl-2.

PMID- 22363271
TI  - On-Center/Inhibitory-Surround Decorrelation via Intraglomerular Inhibition in the
      Olfactory Bulb Glomerular Layer.
AB  - Classical lateral inhibition, which relies on spatially ordered neural
      representations of physical stimuli, cannot decorrelate sensory representations
      in which stimulus properties are represented non-topographically. Recent
      theoretical and experimental studies indicate that such a non-topographical
      representation of olfactory stimuli predominates in olfactory bulb, thereby
      refuting the classical view that olfactory decorrelation is mediated by lateral
      inhibition comparable to that in the retina. Questions persist, however,
      regarding how well non-topographical decorrelation models can replicate the
      inhibitory "surround" that has been observed experimentally (with respect to odor
      feature-similarity) in olfactory bulb principal neurons, analogous to the spatial
      inhibitory surround generated by lateral inhibition in retina. Using two
      contrasting scenarios of stimulus representation - one "retinotopically"
      organized and one in which receptive fields are unpredictably distributed as they
      are in olfactory bulb - we here show that intracolumnar inhibitory interactions
      between local interneurons and principal neurons successfully decorrelate similar
      sensory representations irrespective of the scenario of representation. In
      contrast, lateral inhibitory interactions between these same neurons in
      neighboring columns are only able to effectively decorrelate topographically
      organized representations. While anatomical substrates superficially consistent
      with both types of inhibition exist in olfactory bulb, of the two only local
      intraglomerular inhibition suffices to mediate olfactory decorrelation.

PMID- 22363272
TI  - Conflict Processing in the Rat Brain: Behavioral Analysis and Functional MUPET
      Imaging Using [F]Fluorodeoxyglucose.
AB  - Conflicts in spatial stimulus-response tasks occur when the task-relevant feature
      of a stimulus implies a response toward a certain location which does not match
      the location of stimulus presentation. This conflict leads to increased error
      rates and longer reaction times, which has been termed Simon effect. A model of
      dual route processing (automatic and intentional) of stimulus features has been
      proposed, predicting response conflicts if the two routes are incongruent.
      Although there is evidence that the prefrontal cortex, notably the anterior
      cingulate cortex (ACC), plays a crucial role in conflict processing, the neuronal
      basis of dual route architecture is still unknown. In this study, we pursue a
      novel approach using positron emission tomography (PET) to identify relevant
      brain areas in a rat model of an auditory Simon task, a neuropsychological
      interference task, which is commonly used to study conflict processing in humans.
      For combination with PET we used the metabolic tracer [(18)F]fluorodeoxyglucose,
      which accumulates in metabolically active brain cells during the behavioral task.
      Brain areas involved in conflict processing are supposed to be activated when
      automatic and intentional route processing lead to different responses (dual
      route model). Analysis of PET data revealed specific activation patterns for
      different task settings applicable to the dual route model as established for
      response conflict processing. The rat motor cortex (M1) may be part of the
      automatic route or involved in its facilitation, while premotor (M2), prelimbic,
      and ACC seemed to be essential for inhibiting the incorrect, automatic response,
      indicating conflict monitoring functions. Our findings and the remarkable
      similarities to the pattern of activated regions reported during conflict
      processing in humans demonstrate that our rodent model opens novel opportunities
      to investigate the anatomical basis of conflict processing and dual route
      architecture.

PMID- 22363273
TI  - Brain structural and functional correlates of resilience to Bipolar Disorder.
AB  - BACKGROUND: Resilient adaptation can be construed in different ways, but as used
      here it refers to adaptive brain responses associated with avoidance of
      psychopathology despite expressed genetic predisposition to Bipolar Disorder
      (BD). Although family history of BD is associated with elevated risk of affective
      morbidity a significant proportion of first-degree relatives remain free of
      psychopathology. Examination of brain structure and function in these individuals
      may inform on adaptive responses that pre-empt disease expression. METHODS: Data
      presented here are derived from the Vulnerability to Bipolar Disorders Study
      (VIBES) which includes BD patients, asymptomatic relatives and controls.
      Participants underwent extensive investigations including brain structural (sMRI)
      and functional magnetic resonance imaging (fMRI). We present results from sMRI
      voxel-based-morphometry and from conventional and connectivity analyses of fMRI
      data obtained during the Stroop Colour Word Test (SCWT), a task of cognitive
      control during conflict resolution. All analyses were implemented using
      Statistical Parametric Mapping software version 5 (SPM5). Resilience in relatives
      was operationalized as the lifetime absence of clinical-range symptoms. RESULTS:
      Resilient relatives of BD patients expressed structural, functional, and
      connectivity changes reflecting the effect of genetic risk on the brain. These
      included increased insular volume, decreased activation within the posterior and
      inferior parietal regions involved in selective attention during the SCWT, and
      reduced fronto-insular and fronto-cingulate connectivity. Resilience was
      associated with increased cerebellar vermal volume and enhanced functional
      coupling between the dorsal and the ventral prefrontal cortex during the SCWT.
      CONCLUSIONS: Our findings suggests the presence of biological mechanisms
      associated with resilient adaptation of brain networks and pave the way for the
      identification of outcome-specific trajectories given a bipolar genotype.

PMID- 22363275
TI  - Sculpting the brain.
AB  - Neuroculture, conceived as the reciprocal interaction between neuroscience and
      different areas of human knowledge is influencing our lives under the prism of
      the latest neuroscientific discoveries. Simultaneously, neuroculture can create
      new models of thinking that can significantly impact neuroscientists' daily
      practice. Especially interesting is the interaction that takes place between
      neuroscience and the arts. This interaction takes place at different, infinite
      levels and contexts. I contextualize my work inside this neurocultural framework.
      Through my artwork, I try to give a more natural vision of the human brain, which
      could help to develop a more humanistic culture.

PMID- 22363274
TI  - Early dissociation between neural signatures of endogenous spatial attention and
      perceptual awareness during visual masking.
AB  - THE RELATIONSHIP BETWEEN SPATIAL ATTENTION AND CONSCIOUS ACCESS HAS OFTEN BEEN
      PICTURED AS A SINGLE CAUSAL LINK: spatial attention would provide conscious
      access to weak stimuli by increasing their effective contrast during early visual
      processing. To test this hypothesis, we assessed whether the early attentional
      amplification of visual responses, around 100 ms following stimulus onset, had a
      decisive impact on conscious detection. We recorded magnetoencephalographic (MEG)
      signals while participants focused their attention toward or away from masked
      stimuli which were physically identical but consciously detected half of the
      time. Spatial attention increased the amplitude of early occipital responses
      identically for both detected and missed stimuli around 100 ms, and therefore,
      did not control conscious access. Accordingly, spatial attention did not increase
      the proportion of detected stimuli. The earliest neuromagnetic correlate of
      conscious detection, around 120 ms over the contralateral temporal cortex, was
      independent from the locus of attention. This early activation combined objective
      information about stimulus presence and subjective information about stimulus
      visibility, and was followed by a late correlate of conscious reportability, from
      220 ms over temporal and frontal cortex, which correlated exclusively with
      stimulus visibility. This widespread activation coincided in time with the
      reorienting of attention triggered by masks presented at the uncued location.
      This reorienting was stronger and occurred earlier when the masked stimulus was
      detected, suggesting that the conscious detection of a masked stimulus at an
      unexpected location captures spatial attention. Altogether, these results support
      a double dissociation between the neural signatures of endogenous spatial
      attention and perceptual awareness.

PMID- 22363276
TI  - Beyond natural numbers: negative number representation in parietal cortex.
AB  - Unlike natural numbers, negative numbers do not have natural physical referents.
      How does the brain represent such abstract mathematical concepts? Two competing
      hypotheses regarding representational systems for negative numbers are a rule
      based model, in which symbolic rules are applied to negative numbers to translate
      them into positive numbers when assessing magnitudes, and an expanded magnitude
      model, in which negative numbers have a distinct magnitude representation. Using
      an event-related functional magnetic resonance imaging design, we examined brain
      responses in 22 adults while they performed magnitude comparisons of negative and
      positive numbers that were quantitatively near (difference <4) or far apart
      (difference >6). Reaction times (RTs) for negative numbers were slower than
      positive numbers, and both showed a distance effect whereby near pairs took
      longer to compare. A network of parietal, frontal, and occipital regions were
      differentially engaged by negative numbers. Specifically, compared to positive
      numbers, negative number processing resulted in greater activation bilaterally in
      intraparietal sulcus (IPS), middle frontal gyrus, and inferior lateral occipital
      cortex. Representational similarity analysis revealed that neural responses in
      the IPS were more differentiated among positive numbers than among negative
      numbers, and greater differentiation among negative numbers was associated with
      faster RTs. Our findings indicate that despite negative numbers engaging the IPS
      more strongly, the underlying neural representation are less distinct than that
      of positive numbers. We discuss our findings in the context of the two
      theoretical models of negative number processing and demonstrate how multivariate
      approaches can provide novel insights into abstract number representation.

PMID- 22363277
TI  - Magnocellular training improves visual word recognition.
AB  - Current research has shown that basic visual networks, such as the magnocellular
      system, may play a crucial role in reading deficits related to dyslexia. The
      current study explored the relationship between magnocellular activity and
      reading abilities; we examined the hypothesis that a repeated usage of the
      magnocellular stream may improve reading by strengthening crucial neural
      pathways. Visual training was conducted for five consecutive days using a motion
      detection task (magnocellular training) and a control task of pattern detection
      (parvocellular training). Reading abilities of skilled readers were measured
      before and after the training using a lexical decision task. It was found that
      low-grade visual training overall can improve speed of lexical decision, but
      there is some indication that magnocellular training may selectively relate to
      accuracy. This potential added benefit of accuracy is crucial, and indicates that
      magnocellular training may have an advantage to parvocellular or general visual
      training when it comes to reading. This result lends support to the role of basic
      visual systems in reading, and has potential implications for neurorehabilitation
      of reading-related deficits.

PMID- 22363278
TI  - Regular, brief mindfulness meditation practice improves electrophysiological
      markers of attentional control.
AB  - Mindfulness-based meditation practices involve various attentional skills,
      including the ability to sustain and focus ones attention. During a simple
      mindful breathing practice, sustained attention is required to maintain focus on
      the breath while cognitive control is required to detect mind wandering. We thus
      hypothesized that regular, brief mindfulness training would result in
      improvements in the self-regulation of attention and foster changes in neuronal
      activity related to attentional control. A longitudinal randomized control group
      EEG study was conducted. At baseline (T1), 40 meditation naive participants were
      randomized into a wait list group and a meditation group, who received three
      hours mindfulness meditation training. Twenty-eight participants remained in the
      final analysis. At T1, after eight weeks (T2) and after 16 weeks (T3), all
      participants performed a computerized Stroop task (a measure of attentional
      control) while the 64-channel EEG was recorded. Between T1 and T3 the meditators
      were requested to meditate daily for 10 min. Event-related potential (ERP)
      analysis highlighted two between group effects that developed over the course of
      the 16-week mindfulness training. An early effect at left and right posterior
      sites 160-240 ms post-stimulus indicated that meditation practice improved the
      focusing of attentional resources. A second effect at central posterior sites 310
      380 ms post-stimulus reflects that meditation practice reduced the recruitment of
      resources during object recognition processes, especially for incongruent
      stimuli. Scalp topographies and source analyses (Variable Resolution
      Electromagnetic Tomography, VARETA) indicate relevant changes in neural sources,
      pertaining to left medial and lateral occipitotemporal areas for the early effect
      and right lateral occipitotemporal and inferior temporal areas for the later
      effect. The results suggest that mindfulness meditation may alter the efficiency
      of allocating cognitive resources, leading to improved self-regulation of
      attention.

PMID- 22363279
TI  - Repetitive TMS suggests a role of the human dorsal premotor cortex in action
      prediction.
AB  - Predicting the actions of other individuals is crucial for our daily
      interactions. Recent evidence suggests that the prediction of object-directed arm
      and full-body actions employs the dorsal premotor cortex (PMd). Thus, the neural
      substrate involved in action control may also be essential for action prediction.
      Here, we aimed to address this issue and hypothesized that disrupting the PMd
      impairs action prediction. Using fMRI-guided coil navigation, rTMS (five pulses,
      10 Hz) was applied over the left PMd and over the vertex (control region) while
      participants observed everyday actions in video clips that were transiently
      occluded for 1 s. The participants detected manipulations in the time course of
      occluded actions, which required them to internally predict the actions during
      occlusion. To differentiate between functional roles that the PMd could play in
      prediction, rTMS was either delivered at occluder-onset (TMS-early), affecting
      the initiation of action prediction, or 300 ms later during occlusion (TMS-late),
      affecting the maintenance of an ongoing prediction. TMS-early over the left PMd
      produced more prediction errors than TMS-early over the vertex. TMS-late had no
      effect on prediction performance, suggesting that the left PMd might be involved
      particularly during the initiation of internally guided action prediction but may
      play a subordinate role in maintaining ongoing prediction. These findings open a
      new perspective on the role of the left PMd in action prediction which is in line
      with its functions in action control and in cognitive tasks. In the discussion,
      the relevance of the left PMd for integrating external action parameters with the
      observer's motor repertoire is emphasized. Overall, the results are in line with
      the notion that premotor functions are employed in both action control and action
      observation.

PMID- 22363280
TI  - Optokinetic stimulation modulates neglect for the number space: evidence from
      mental number interval bisection.
AB  - Behavioral, neuropsychological, and neuroimaging data support the idea that
      numbers are represented along a mental number line (MNL), an analogical,
      visuospatial representation of number magnitude. The MNL is left-to-right
      oriented in Western cultures, with small numbers on the left and larger numbers
      on the right. Left neglect patients are impaired in the mental bisection of
      numerical intervals, with a bias toward larger numbers that are relatively to the
      right on the MNL. In the present study we investigated the effects of optokinetic
      stimulation (OKS) - a technique inducing visuospatial attention shifts by means
      of activation of the optokinetic nystagmus - on number interval bisection. One
      patient with left neglect following right-hemisphere stroke (BG) and four control
      patients with right-hemisphere damage, but without neglect, performed the number
      interval bisection task in three conditions of OKS: static, leftward, and
      rightward. In the static condition, BG misbisected to the right of the true
      midpoint. BG misbisected to the left following leftward OKS, and again to the
      right of the midpoint following rightward OKS. Moreover, the variability of BG's
      performance was smaller following both leftward and rightward OKS, suggesting
      that the attentional bias induced by OKS reduced the "indifference zone" that is
      thought to underlie the length effect reported in bisection tasks. We argue that
      shifts of visuospatial attention, induced by OKS, may affect number interval
      bisection, thereby revealing an interaction between the processing of the
      perceptual space and the processing of the number space.

PMID- 22363282
TI  - Maintaining live discussion in two-stage open peer review.
AB  - Open peer review has been proposed for a number of reasons, in particular, for
      increasing the transparency of the article selection process for a journal, and
      for obtaining a broader basis for feedback to the authors and for the acceptance
      decision. The review discussion may also in itself have a value for the research
      community. These goals rely on the existence of a lively review discussion, but
      several experiments with open-process peer review in recent years have
      encountered the problem of faltering review discussions. The present article
      addresses the question of how lively review discussion may be fostered by
      relating the experience of the journal Electronic Transactions on Artificial
      Intelligence (ETAI) which was an early experiment with open peer review. Factors
      influencing the discussion activity are identified. It is observed that it is
      more difficult to obtain lively discussion when the number of contributed
      articles increases, which implies difficulties for scaling up the open peer
      review model. Suggestions are made for how this difficulty may be overcome.

PMID- 22363281
TI  - Verbal to visual code switching improves working memory in older adults: an fMRI
      study.
AB  - The effect of verbal to visual code switching training on working memory
      performance was investigated in individuals aged 63 and older. During verbal
      working memory task performance, the training group (n = 25) was introduced to a
      verbal to visual code switching strategy while the control group (n = 25) was not
      exposed to such a strategy. Working memory recognition accuracy was enhanced only
      in the training group. To explore the neural substrates underlying these strategy
      effects, fMRI was used to measure brain activity in both groups during working
      memory task performance before and after an attention training period. In a
      comparison between pre- and post-training sessions, results showed increased
      activation in the anterior cingulate cortex (ACC). Relative to the control group,
      the post-training group exhibited increased activation in the left and right
      inferior parietal lobules (IPLs) and right superior parietal lobule (SPL). These
      findings suggest that use of a verbal to visual code switching strategy may
      assist older individuals in the maintenance of information in working memory.

PMID- 22363283
TI  - Immunological response as a source to variability in drug metabolism and
      transport.
AB  - Through the last decades it has become increasingly evident that disease-states
      involving cytokines affect the pharmacokinetics of drugs through regulation of
      expression and activity of drug metabolizing enzymes, and more recently also drug
      transporters. The clinical implication is however difficult to predict, since
      these effects are dependent on the degree of inflammation and may be changed when
      the diseases are treated. This article will give an overview of the present
      understanding of the effects of cytokines on cytochrome P450 enzymes and drug
      transporters, and highlight the importance of considering these issues in regard
      to increasing use of the relatively new class of drugs, namely therapeutic
      proteins.

PMID- 22363284
TI  - Microglia function in Alzheimer's disease.
AB  - Contrary to early views, we now know that systemic inflammatory/immune responses
      transmit to the brain. The microglia, the resident "macrophages" of the brain's
      innate immune system, are most responsive, and increasing evidence suggests that
      they enter a hyper-reactive state in neurodegenerative conditions and aging. As
      sustained over-production of microglial pro-inflammatory mediators is neurotoxic,
      this raises great concern that systemic inflammation (that also escalates with
      aging) exacerbates or possibly triggers, neurological diseases (Alzheimer's,
      prion, motoneuron disease). It is known that inflammation has an essential role
      in the progression of Alzheimer's disease (AD), since amyloid-beta (Abeta) is
      able to activate microglia, initiating an inflammatory response, which could have
      different consequences for neuronal survival. On one hand, microglia may delay
      the progression of AD by contributing to the clearance of Abeta, since they
      phagocyte Abeta and release enzymes responsible for Abeta degradation. Microglia
      also secrete growth factors and anti-inflammatory cytokines, which are
      neuroprotective. In addition, microglia removal of damaged cells is a very
      important step in the restoration of the normal brain environment, as if left
      such cells can become potent inflammatory stimuli, resulting in yet further
      tissue damage. On the other hand, as we age microglia become steadily less
      efficient at these processes, tending to become over-activated in response to
      stimulation and instigating too potent a reaction, which may cause neuronal
      damage in its own right. Therefore, it is critical to understand the state of
      activation of microglia in different AD stages to be able to determine the effect
      of potential anti-inflammatory therapies. We discuss here recent evidence
      supporting both the beneficial or detrimental performance of microglia in AD, and
      the attempt to find molecules/biomarkers for early diagnosis or therapeutic
      interventions.

PMID- 22363285
TI  - Role and Therapeutic Potential of the Pro-Longevity Factor FOXO and Its
      Regulators in Neurodegenerative Disease.
AB  - Studies in simple model organisms have yielded crucial insights into the genetic
      and molecular aspects of longevity. FOXO, which is most notable for its
      association with longevity, and its upstream regulators such as sirtuins have
      received particular attention in translational research because these genes
      modulate cell survival in several models of neurodegenerative diseases. There is
      a large amount of knowledge on the pathways that regulate FOXO activity and genes
      that may be regulated by FOXO. However, for the same reason that the FOXO network
      is a complex stress response system, its therapeutic potential to develop disease
      modifying strategies requires further examination. Although the FOXO network
      contains druggable genes such as sirtuins and AMPK, whether they should be
      activated or inhibited and whether protection against the early or late phases of
      neuronal cell decline might require opposite therapeutic strategies remains
      unclear. Additionally, the mode of action of small compound molecules believed to
      act on FOXO network targets was questioned. This review recapitulates essential
      facts and questions about the promises of FOXO and its interactors in
      neurodegenerative disease.

PMID- 22363286
TI  - Structures, substrates, and regulators of Mammalian sirtuins - opportunities and
      challenges for drug development.
AB  - Sirtuins are NAD(+)-dependent protein deacetylases regulating metabolism, stress
      responses, and aging processes. Mammalia have seven Sirtuin isoforms, Sirt1-7,
      which differ in their substrate specificities and subcellular localizations. The
      physiological functions of Sirtuins make them interesting therapeutic targets,
      which has stimulated extensive efforts on development of small molecule Sirtuin
      modulators. Yet, most Sirtuin inhibitors show limited potency and/or isoform
      specificity, and the mechanism of Sirtuin activation by small molecules remains
      obscure. Accumulating information on Sirtuin substrates, structures, and
      regulation mechanisms offer new opportunities for the challenging task to develop
      potent and specific small molecule modulators for mammalian Sirtuins for in vivo
      studies and therapeutic applications. We therefore recapitulate advances in
      structural and mechanistic studies on substrate recognition and deacetylation by
      Sirtuins, and in the characterization of compounds and molecular mechanisms
      regulating their activity. We then discuss challenges and opportunities from
      these findings for Sirtuin-targeted drug development efforts.

PMID- 22363287
TI  - Sirtuins, metabolism, and cancer.
AB  - More than a decade ago, sirtuins were discovered as a highly conserved family of
      NAD(+)-dependent enzymes that extend lifespan in lower organisms. In mammals,
      sirtuins are key regulators of stress responses and metabolism, influencing a
      range of diseases, including diabetes, neurodegeneration, and cancer. In recent
      years, new functions of sirtuins have been characterized, uncovering the
      underlying mechanisms of their multifaceted role in metabolism. Here, we
      specifically review recent progress on the role of sirtuins in DNA repair and
      energy metabolism, further discussing the implication of sirtuins in the biology
      of cancer.

PMID- 22363288
TI  - Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous
      Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT
      Sub-Study with PET and MRI.
AB  - PURPOSE: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST
      segment elevation myocardial infarct (STEMI) are largely unknown in humans.
      Therefore, we evaluated the feasibility of serial positron emission tomography
      (PET) and MRI studies to provide insight into the effects of BMCs on the healing
      process of ischemic myocardial damage. METHODS: Nineteen patients with successful
      primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were
      randomized for BMC therapy (2.9 * 10(6) CD34+ cells) or placebo after bone marrow
      aspiration in a double-blind, multi-center study. Three days post-MI, coronary
      angioplasty, and paclitaxel eluting stent implantation preceded either BMC or
      placebo therapy. Cardiac PET and MRI studies were performed 7-12 days after
      therapies and repeated after 6 months, and images were analyzed at a central core
      laboratory. RESULTS: In BMC-treated patients, there was a decrease in [(11)C]-HED
      defect size (-4.9 +/- 4.0 vs. -1.6 +/- 2.2%, p = 0.08) and an increase in [(18)F]
      FDG uptake in the infarct area at risk (0.06 +/- 0.09 vs. -0.05 +/- 0.16, p =
      0.07) compared to controls, as well as less left ventricular dilatation (-4.4 +/-
      13.3 vs. 8.0 +/- 16.7 mL/m(2), p = 0.12) at 6 months follow-up. However, BMC
      treatment was inferior to placebo in terms of changes in rest perfusion in the
      area at risk (-0.09 +/- 0.17 vs. 0.10 +/- 0.17, p = 0.03) and infarct size (0.4
      +/- 4.2 vs. -5.1 +/- 5.9 g, p = 0.047), and no effect was observed on ejection
      fraction (p = 0.37). CONCLUSION: After the acute phase of STEMI, BMC therapy
      showed only minor trends of long-term benefit in patients with rapid successful
      thrombolysis. There was a trend of more decrease in innervation defect size and
      enhanced glucose metabolism in the infarct-related myocardium and also a trend of
      less ventricular dilatation in the BMC-treated group compared to placebo.
      However, no consistently better outcome was observed in the BMC-treated group
      compared to placebo.

PMID- 22363290
TI  - Experimental Mapping of the Canine KCNJ2 and KCNJ12 Gene Structures and
      Functional Analysis of the Canine K(IR)2.2 ion Channel.
AB  - For many model organisms traditionally in use for cardiac electrophysiological
      studies, characterization of ion channel genes is lacking. We focused here on two
      genes encoding the inward rectifier current, KCNJ2 and KCNJ12, in the dog heart.
      A combination of RT-PCR, 5'-RACE, and 3'-RACE demonstrated the status of KCNJ2 as
      a two exon gene. The complete open reading frame (ORF) was located on the second
      exon. One transcription initiation site was mapped. Four differential
      transcription termination sites were found downstream of two consensus
      polyadenylation signals. The canine KCNJ12 gene was found to consist of three
      exons, with its ORF located on the third exon. One transcription initiation and
      one termination site were found. No alternative splicing was observed in right
      ventricle or brain cortex. The gene structure of canine KCNJ2 and KCNJ12 was
      conserved amongst other vertebrates, while current GenBank gene annotation was
      determined as incomplete. In silico translation of KCN12 revealed a non-conserved
      glycine rich stretch located near the carboxy-terminus of the K(IR)2.2 protein.
      However, no differences were observed when comparing dog with human K(IR)2.2
      protein upon ectopic expression in COS-7 or HEK293 cells with respect to
      subcellular localization or electrophysiological properties.

PMID- 22363292
TI  - Extrasynaptic neurotransmission as a way of modulating neuronal functions.

PMID- 22363289
TI  - The Membrane-Bound Aspartyl Protease BACE1: Molecular and Functional Properties
      in Alzheimer's Disease and Beyond.
AB  - The beta-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease
      involved in Alzheimer's disease (AD) pathogenesis and in myelination. BACE1
      initiates the generation of the pathogenic amyloid beta-peptide, which makes
      BACE1 a major drug target for AD. BACE1 also cleaves and activates neuregulin 1,
      thereby contributing to postnatal myelination, in particular in the peripheral
      nervous system. Additional proteins are also cleaved by BACE1, but less is known
      about the physiological consequences of their cleavage. Recently, new phenotypes
      were described in BACE1-deficient mice. Although it remains unclear through which
      BACE1 substrates they are mediated, the phenotypes suggest a versatile role of
      this protease for diverse physiological processes. This review summarizes the
      enzymatic and cellular properties of BACE1 as well as its regulation by lipids,
      by transcriptional, and by translational mechanisms. The main focus will be on
      the recent progress in understanding BACE1 function and its implication for
      potential mechanism-based side effects upon therapeutic inhibition.

PMID- 22363293
TI  - Challenges for the Therapeutic use of Pluripotent Stem Derived Cells.
AB  - Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) are
      an attractive cell source for regenerative medicine. These cells can be expanded
      to vast numbers and can be differentiated to many desired pluripotent stem cells
      (PSC) derived therapeutic cells. Cell replacement bears promises, but also
      challenges. The introduction of exogenous cells in a recipient must address
      several different topics; its safety, the exclusion of tumor formation, the
      immunological response and possible rejection, the cells cleanliness and their
      biological quality, and quantity representing the functionality of the PSC
      derived therapeutic cells. Tumor formation requires the removal of any PSC
      remaining after differentiation. Immunological rejection can be addressed with
      immunomodulation of the cells and the recipient. Cleanliness can be optimized
      using good manufacturing practice quality systems. At last, the functionality of
      the cells must be tested in in vitro and in animal models. After addressing these
      challenges, precise strategies are developed to monitor the status of the cells
      at different times and in case of undesired results, corresponding counteracting
      strategies must exist before any clinical attempt.

PMID- 22363291
TI  - Biological Significance of Local TGF-beta Activation in Liver Diseases.
AB  - The cytokine transforming growth factor-beta (TGF-beta) plays a pivotal role in a
      diverse range of cellular responses, including cell proliferation, apoptosis,
      differentiation, migration, adhesion, angiogenesis, stimulation of extracellular
      matrix (ECM) synthesis, and downregulation of ECM degradation. TGF-beta and its
      receptors are ubiquitously expressed by most cell types and tissues in vivo. In
      intact adult tissues and organs, TGF-beta is secreted in a biologically inactive
      (latent) form associated in a non-covalent complex with the ECM. In response to
      injury, local latent TGF-beta complexes are converted into active TGF-beta
      according to a tissue- and injury type-specific activation mechanism. Such a well
      and tightly orchestrated regulation in TGF-beta activity enables an immediate,
      highly localized response to type-specific tissue injury. In the pathological
      process of liver fibrosis, TGF-beta plays as a master profibrogenic cytokine in
      promoting activation and myofibroblastic differentiation of hepatic stellate
      cells, a central event in liver fibrogenesis. Continuous and/or persistent TGF
      beta signaling induces sustained production of ECM components and of tissue
      inhibitor of metalloproteinase synthesis. Therefore, the regulation of locally
      activated TGF-beta levels is increasingly recognized as a therapeutic target for
      liver fibrogenesis. This review summarizes our present knowledge of the
      activation mechanisms and bioavailability of latent TGF-beta in biological and
      pathological processes in the liver.

PMID- 22363294
TI  - Characterization of Aquaporin 4 Protein Expression and Localization in Tissues of
      the Dogfish (Squalus acanthias).
AB  - The role of aquaporin water channels such as aquaporin 4 (Aqp4) in elasmobranchs
      such as the dogfish Squalus acanthias is completely unknown. This investigation
      set out to determine the expression and cellular and sub-cellular localization of
      Aqp4 protein in dogfish tissues. Two polyclonal antibodies were generated (AQP4/1
      and AQP4/2) and these showed somewhat different characteristics in Western
      blotting and immunohistochemistry. Western blots using the AQP4/1 antibody showed
      two bands (35.5 and 49.5 kDa) in most tissues in a similar fashion to mammals.
      Liver had an additional band of 57 kDa and rectal gland two further faint bands
      of 37.5 and 38.5 kDa. However, unlike in mammals, Aqp4 protein was ubiquitously
      expressed in all tissues including gill and liver. The AQP4/2 antibody appeared
      much less specific in Western blots. Both antibodies were used in
      immunohistochemistry and showed similar cellular localizations, although the
      AQP4/2 antibody had a more restricted sub-cellular distribution compared to
      AQP4/1 and therefore appeared to be more specific for Aqp4. In kidney a sub-set
      of tubules were stained which may represent intermediate tubule segments (In-III
      In-VI). AQP4/1 and AQP4/2 antibodies localized to the same tubules segments in
      serial sections although the intensity and sub-cellular distribution were
      different. AQP4/2 showed a basal or basolateral membrane distribution whereas
      AQP4/1 was often distributed throughout the whole cell including the nuclear
      region. In rectal gland and cardiac stomach Aqp4 was localized to secretory
      tubules but again AQP/1 and AQP/2 exhibited different sub-cellular distributions.
      In gill, both antibodies stained large cells in the primary filament and
      secondary lamellae. Again AQP4/1 antibody stained most or all the cell including
      the nucleus, whereas AQP4/2 had a plasma membrane or plasma membrane and
      cytoplasmic distribution. Two types of large mitochondrial rich transport cells
      are known to exist in elasmobranchs, that express either Na, K-ATPase, or V-type
      ATPase ion transporters. Using Na, K-ATPase, and V-type ATPase antibodies, Aqp4
      was colocalized with these proteins using the AQP4/1 antibody. Results show Aqp4
      is expressed in both (and all) branchial Na, K-ATPase, and V-type ATPase
      expressing cells.

PMID- 22363295
TI  - Gene Mutations Resulting in the Development of ARVC/D Could Affect Cells of the
      Cardiac Conduction System.
AB  - In contrast to epithelial cells, cardiomyocytes are connected by complex hybrid
      type adhering junctions, termed composite junctions (areae compositae). Composite
      junctions are found to be composed of typical desmosomal as well as adherens
      junction proteins. Therefore, in adult mammalian cardiomyocytes desmosomal
      proteins are not restricted to the relatively small desmosomes but are indirectly
      involved in anchoring the myofibrillar actin filaments. Subsequent investigations
      revealed that the formation of composite junctions is a rather late event during
      mammalian heart development and vertebrate heart evolution. Nascent, more round
      shaped cardiomyocytes of early developmental stages are connected by desmosomes
      and separate adherens junctions quite similar to cells of epithelial origin.
      During progression of development both types of adhering junctions seem to
      gradually fuse at the two poles of the mature mammalian cardiomyocytes to
      establish the hybrid-type composite junctions. Recently, we demonstrated that the
      specialized cardiomyocytes of the cardiac conduction system exhibit high amounts
      of desmosomes, not fully established composite junctions and adherens junctions.
      This underlines the fact that cells of the cardiac conduction system are known to
      resemble cardiomyocytes in their nascent state and do not undergo working
      myocardial differentiation. However, the astonishing high amount of desmosomal
      protein containing adhering junctions connecting, e.g., Purkinje fibers raises
      the possibility that pacemaker and conductive tissue may be affected by
      desmosomal gene mutations in ARVC/D patients.

PMID- 22363296
TI  - Hepatoprotectant ursodeoxycholyl lysophosphatidylethanolamide increasing
      phosphatidylcholine levels as a potential therapy of acute liver injury.
AB  - It has been long known that hepatic synthesis of phosphatidylcholine (PC) is
      depressed during acute such as carbon tetrachloride-induced liver injury. Anti
      hepatotoxic properties of PC as liposomes have been recognized for treatment of
      acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in
      stabilizing cellular membrane. For therapeutic management of liver injury, we
      coupled UDCA with a phospholipid known as ursodeoxycholyl
      lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in
      class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial
      damage and apoptosis, elicits survival signaling pathway, and promotes
      regeneration of hepatocytes. We herein report that a unique contribution of UDCA
      LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated
      hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the
      hydrolysis to LPE which was not the precursor of the increased PC. The levels of
      PC in the liver and blood were increased rapidly after intraperitoneally
      administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC
      synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased
      transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing
      phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a
      hepatoprotectant was able to induce synthesis of protective PC which would
      supplement for the loss of PC occurring during acute liver injury. This property
      has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such
      as acetaminophen poisoning.

PMID- 22363298
TI  - Evidence and consequences of the central role of the kidneys in the
      pathophysiology of sympathetic hyperactivity.
AB  - Chronic elevation of the sympathetic nervous system has been identified as a
      major contributor to the complex pathophysiology of hypertension, states of
      volume overload - such as heart failure - and progressive kidney disease. It is
      also a strong determinant for clinical outcome. This review focuses on the
      central role of the kidneys in the pathogenesis of sympathetic hyperactivity. As
      a consequence, renal denervation may be an attractive option to treat sympathetic
      hyperactivity. The review will also focus on first results and the still
      remaining questions of this new treatment option.

PMID- 22363297
TI  - Remote ischemic conditioning: from bench to bedside.
AB  - Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting
      organs or tissue against the detrimental effects of acute ischemia-reperfusion
      injury (IRI). It describes an endogenous phenomenon in which the application of
      one or more brief cycles of non-lethal ischemia and reperfusion to an organ or
      tissue protects a remote organ or tissue from a sustained episode of lethal IRI.
      Although RIC protection was first demonstrated to protect the heart against acute
      myocardial infarction, its beneficial effects are also seen in other organs
      (lung, liver, kidney, intestine, brain) and tissues (skeletal muscle) subjected
      to acute IRI. The recent discovery that RIC can be induced non-invasively by
      simply inflating and deflating a standard blood pressure cuff placed on the upper
      arm or leg, has facilitated its translation into the clinical setting, where it
      has been reported to be beneficial in a variety of cardiac scenarios. In this
      review article we provide an overview of RIC, the potential underlying
      mechanisms, and its potential as a novel therapeutic strategy for protecting the
      heart and other organs from acute IRI.

PMID- 22363299
TI  - Endothelial progenitor cells enter the aging arena.
AB  - Age is a significant risk factor for the development of vascular diseases, such
      as atherosclerosis. Although pharmacological treatments, including statins and
      anti-hypertensive drugs, have improved the prognosis for patients with
      cardiovascular disease, it remains a leading cause of mortality in those aged 65
      years and over. Furthermore, given the increased life expectancy of the
      population in developed countries, there is a clear need for alternative
      treatment strategies. Consequently, the relationship between aging and progenitor
      cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs)
      play an integral role in the cellular repair mechanisms for endothelial
      regeneration and maintenance. However, EPCs are subject to age-associated changes
      that diminish their number in circulation and function, thereby enhancing
      vascular disease risk. A great deal of research is aimed at developing strategies
      to harness the regenerative capacity of these cells. In this review, we discuss
      the current understanding of the cells termed "EPCs," examine the impact of age
      on EPC-mediated repair and identify therapeutic targets with potential for
      attenuating the age-related decline in vascular health via beneficial actions on
      EPCs.

PMID- 22363300
TI  - A Medicinal Herb Scutellaria lateriflora Inhibits PrP Replication in vitro and
      Delays the Onset of Prion Disease in Mice.
AB  - Transmissible spongiform encephalopathies (TSE) are characterized by the
      misfolding of the host encoded prion protein (PrP(C)) into a pathogenic isoform
      (PrP(Sc)) which leads to the accumulation of beta-sheet-rich fibrils and
      subsequent loss of neurons and synaptic functions. Although many compounds have
      been identified which inhibit accumulation or dissolve fibrils and aggregates in
      vitro there is no therapeutic treatment to stop these progressive
      neurodegenerative diseases. Here we describe the effects of the traditional
      medicinal herb Scutellaria lateriflora (S. lateriflora) and its natural
      compounds, the flavonoids baicalein and baicalin, on the development of prion
      disease using in vitro and in vivo models. S. lateriflora extract as well as both
      constituents reduced the PrP(res) accumulation in scrapie-infected cell cultures
      and cell-free conversion assays and lead to the destabilization of pre-existing
      PrP(Sc) fibrils. Moreover, tea prepared from S. lateriflora, prolonged
      significantly the incubation time of scrapie-infected mice upon oral treatment.
      Therefore S. lateriflora extracts as well as the individual compounds can be
      considered as promising candidates for the development of new therapeutic drugs
      against TSEs and other neurodegenerative diseases like Alzheimer's and
      Parkinson's disease.

PMID- 22363301
TI  - Adaptation to antifaces and the perception of correct famous identity in an
      average face.
AB  - Previous experiments have examined exposure to anti-identities (faces that
      possess traits opposite to an identity through a population average), finding
      that exposure to antifaces enhances recognition of the plus-identity images. Here
      we examine adaptation to antifaces using famous female celebrities. We
      demonstrate: that exposure to a color and shape transformed antiface of a
      celebrity increases the likelihood of perceiving the identity from which the
      antiface was manufactured in a composite face and that the effect shows size
      invariance (experiment 1), equivalent effects are seen in internet and laboratory
      based studies (experiment 2), adaptation to shape-only antifaces has stronger
      effects on identity recognition than adaptation to color-only antifaces
      (experiment 3), and exposure to male versions of the antifaces does not influence
      the perception of female faces (experiment 4). Across these studies we found an
      effect of order where aftereffects were more pronounced in early than later
      trials. Overall, our studies delineate several aspects of identity aftereffects
      and support the proposal that identity is coded relative to other faces with
      special reference to a relatively sex-specific mean face representation.

PMID- 22363302
TI  - The frozen face effect: why static photographs may not do you justice.
AB  - When a video of someone speaking is paused, the stationary image of the speaker
      typically appears less flattering than the video, which contained motion. We call
      this the frozen face effect (FFE). Here we report six experiments intended to
      quantify this effect and determine its cause. In Experiment 1, video clips of
      people speaking in naturalistic settings as well as all of the static frames that
      composed each video were presented, and subjects rated how flattering each
      stimulus was. The videos were rated to be significantly more flattering than the
      static images, confirming the FFE. In Experiment 2, videos and static images were
      inverted, and the videos were again rated as more flattering than the static
      images. In Experiment 3, a discrimination task measured recognition of the static
      images that composed each video. Recognition did not correlate with flattery
      ratings, suggesting that the FFE is not due to better memory for particularly
      distinct images. In Experiment 4, flattery ratings for groups of static images
      were compared with those for videos and static images. Ratings for the video
      stimuli were higher than those for either the group or individual static stimuli,
      suggesting that the amount of information available is not what produces the FFE.
      In Experiment 5, videos were presented under four conditions: forward motion,
      inverted forward motion, reversed motion, and scrambled frame sequence. Flattery
      ratings for the scrambled videos were significantly lower than those for the
      other three conditions. In Experiment 6, as in Experiment 2, inverted videos and
      static images were compared with upright ones, and the response measure was
      changed to perceived attractiveness. Videos were rated as more attractive than
      the static images for both upright and inverted stimuli. Overall, the results
      suggest that the FFE requires continuous, natural motion of faces, is not
      sensitive to inversion, and is not due to a memory effect.

PMID- 22363303
TI  - On surprise, change, and the effect of recent outcomes.
AB  - The leading models of human and animal learning rest on the assumption that
      individuals tend to select the alternatives that led to the best recent outcomes.
      The current research highlights three boundaries of this "recency" assumption.
      Analysis of the stock market and simple laboratory experiments suggests that
      positively surprising obtained payoffs, and negatively surprising forgone payoffs
      reduce the rate of repeating the previous choice. In addition, all previous
      trails outcomes, except the latest outcome (most recent), have similar effect on
      future choices. We show that these results, and other robust properties of
      decisions from experience, can be captured with a simple addition to the leading
      models: the assumption that surprise triggers change.

PMID- 22363304
TI  - Picture-Induced Semantic Interference Reflects Lexical Competition during Object
      Naming.
AB  - With a picture-picture experiment, we contrasted competitive and non-competitive
      models of lexical selection during language production. Participants produced
      novel noun-noun compounds in response to two adjacently displayed objects that
      were categorically related or unrelated (e.g., depicted objects: apple and
      cherry; naming response: "apple-cherry"). We observed semantic interference, with
      slower compound naming for related relative to unrelated pictures, very similar
      to interference effects produced by semantically related context words in picture
      word-interference paradigms. This finding suggests that previous failures to
      observe reliable interference induced by context pictures may be due to the
      weakness of lexical activation and competition induced by pictures, relative to
      words. The production of both picture names within one integrated compound word
      clearly enhances lexical activation, resulting in measurable interference
      effects. We interpret this interference as resulting from lexical competition,
      because the alternative interpretation, in terms of response-exclusion from the
      articulatory buffer, does not apply to pictures, even when they are named.

PMID- 22363305
TI  - The role of attention in conscious recollection.
AB  - Most research on the relationship between attention and consciousness has been
      limited to perception. However, perceptions are not the only kinds of mental
      contents of which we can be conscious. An important set of conscious states that
      has not received proper treatment within this discussion is that of memories.
      This paper reviews compelling evidence indicating that attention may be
      necessary, but probably not sufficient, for conscious recollection. However, it
      is argued that unlike the case of conscious perception, the kind of attention
      required during recollection is internal, as opposed to external, attention. As
      such, the surveyed empirical evidence is interpreted as suggesting that internal
      attention is necessary, but probably not sufficient, for conscious recollection.
      The paper begins by justifying the need for clear distinctions among different
      kinds of attention, and then emphasizes the difference between internal and
      external attention. Next, evidence from behavioral, neuropsychological, and
      neuroimaging studies suggesting that internal attention is required for the
      successful retrieval of memorial contents is reviewed. In turn, it is argued that
      internal attention during recollection is what makes us conscious of the contents
      of retrieved memories; further evidence in support of this claim is also
      provided. Finally, it is suggested that internal attention is probably not
      sufficient for conscious recollection. Open questions and possible avenues for
      future research are also mentioned.

PMID- 22363306
TI  - Is coefficient alpha robust to non-normal data?
AB  - Coefficient alpha has been a widely used measure by which internal consistency
      reliability is assessed. In addition to essential tau-equivalence and
      uncorrelated errors, normality has been noted as another important assumption for
      alpha. Earlier work on evaluating this assumption considered either exclusively
      non-normal error score distributions, or limited conditions. In view of this and
      the availability of advanced methods for generating univariate non-normal data,
      Monte Carlo simulations were conducted to show that non-normal distributions for
      true or error scores do create problems for using alpha to estimate the internal
      consistency reliability. The sample coefficient alpha is affected by leptokurtic
      true score distributions, or skewed and/or kurtotic error score distributions.
      Increased sample sizes, not test lengths, help improve the accuracy, bias, or
      precision of using it with non-normal data.

PMID- 22363307
TI  - Against the View that Consciousness and Attention are Fully Dissociable.
AB  - In this paper, I will try to show that the idea that there can be consciousness
      without some form of attention, and high-level top-down attention without
      consciousness, originates from a failure to notice the varieties of forms that
      top-down attention and consciousness can assume. I will present evidence that:
      there are various forms of attention and consciousness; not all forms of
      attention produce the same kind of consciousness; not all forms of consciousness
      are produced by the same kind of attention; there can be low-level attention (or
      preliminary attention), whether of an endogenous or exogenous kind, without
      consciousness; attention cannot be considered the same thing as consciousness.

PMID- 22363308
TI  - Measurement and reliability of response inhibition.
AB  - Response inhibition plays a critical role in adaptive functioning and can be
      assessed with the Stop-signal task, which requires participants to suppress
      prepotent motor responses. Evidence suggests that this ability to inhibit a
      prepotent motor response (reflected as Stop-signal reaction time (SSRT)) is a
      quantitative and heritable measure of interindividual variation in brain
      function. Although attention has been given to the optimal method of SSRT
      estimation, and initial evidence exists in support of its reliability, there is
      still variability in how Stop-signal task data are treated across samples. In
      order to examine this issue, we pooled data across three separate studies and
      examined the influence of multiple SSRT calculation methods and outlier calling
      on reliability (using Intra-class correlation). Our results suggest that an
      approach which uses the average of all available sessions, all trials of each
      session, and excludes outliers based on predetermined lenient criteria yields
      reliable SSRT estimates, while not excluding too many participants. Our findings
      further support the reliability of SSRT, which is commonly used as an index of
      inhibitory control, and provide support for its continued use as a neurocognitive
      phenotype.

PMID- 22363309
TI  - Factors determining semantic facilitation and interference in the cyclic naming
      paradigm.
AB  - The cyclic naming paradigm, in which participants are slower to name pictures
      blocked by semantic category than pictures in an unrelated context, offers a
      window into the dynamics of the mapping between lexical concepts and words. Here
      we provide evidence for the view that incremental adjustments to the connection
      weights from semantics to lexical items provides an elegant explanation of a
      range of observations within the cyclic naming paradigm. Our principal
      experimental manipulation is to vary the within-category semantic distance among
      items that must be named together in a block. In the first set of experiments we
      find that naming latencies are, if anything, faster for within-category
      semantically close blocks compared to within-category semantically far blocks,
      for the first presentation of items. This effect can be explained by the fact
      that there will be more spreading activation, and thus greater priming at the
      lexical level, for within-category semantically close blocks than within-category
      semantically far blocks. We test this explanation by inserting intervening filler
      items (geometric shapes), and show as predicted, that while intervening unrelated
      trials abolish short-lived semantic priming effects, the long-lag interference
      effect that is characteristic of this paradigm is unaffected. These data place
      new constraints on explanations of the cyclic naming effect, and related
      phenomena, within a model of language production.

PMID- 22363310
TI  - Effects of speech rate and practice on the allocation of visual attention in
      multiple object naming.
AB  - Earlier studies had shown that speakers naming several objects typically look at
      each object until they have retrieved the phonological form of its name and
      therefore look longer at objects with long names than at objects with shorter
      names. We examined whether this tight eye-to-speech coordination was maintained
      at different speech rates and after increasing amounts of practice. Participants
      named the same set of objects with monosyllabic or disyllabic names on up to 20
      successive trials. In Experiment 1, they spoke as fast as they could, whereas in
      Experiment 2 they had to maintain a fixed moderate or faster speech rate. In both
      experiments, the durations of the gazes to the objects decreased with increasing
      speech rate, indicating that at higher speech rates, the speakers spent less time
      planning the object names. The eye-speech lag (the time interval between the
      shift of gaze away from an object and the onset of its name) was independent of
      the speech rate but became shorter with increasing practice. Consistent word
      length effects on the durations of the gazes to the objects and the eye-speech
      lags were only found in Experiment 2. The results indicate that shifts of eye
      gaze are often linked to the completion of phonological encoding, but that
      speakers can deviate from this default coordination of eye gaze and speech, for
      instance when the descriptive task is easy and they aim to speak fast.

PMID- 22363311
TI  - Effects of cognitive, motor, and karate training on cognitive functioning and
      emotional well-being of elderly people.
AB  - The present study investigated the influence of cognitive, motor, and Karate
      (accordingly the guidelines of the German-Karate-Federation, DKV) training on the
      cognitive functioning and mental state of older people between 67 and 93 years of
      age. The three training groups each consisted of 12 elderly participants; the
      waiting control group included 9 participants. Before the training, participants
      were evaluated with cognitive measurements (cognitive speed: number-connection
      test, number-symbol test; memory performance: digit-span test, blocking-tapping
      test, figure test) and a measurement of emotional well-being. After this pre
      testing they participated the specific training in on average sixteen 1-h
      training sessions. The cognitive training exercised inductive thinking ability,
      the motor training worked on easy stretching and mobilization techniques, and the
      Karate training taught tasks of self-defense, partner training, and Katas. After
      completion of the training sessions, all tests were applied again. The results
      show no significant difference in cognitive improvement dependent on group
      between the three training conditions. However a significant improvement was
      found in the emotional mental state measurement for the Karate group compared to
      the waiting control group. This result suggests that the integrated involvement
      in Karate leads to a feeling of self-worth and that, even in elderly people,
      integration of new sports helps to improve quality of life.

PMID- 22363312
TI  - Antiplatelet resistance and thromboembolic complications in neurointerventional
      procedures.
AB  - Antiplatelet resistance is emerging as a significant factor in effective
      secondary stroke prevention. Prevalence of aspirin and clopidogrel resistance is
      dependent upon laboratory test and remains contentious. Large studies in
      cardiovascular disease populations have demonstrated worse ischemic outcomes in
      patients with antiplatelet resistance, particularly in patients with coronary
      stents. Thromboembolism is a complication of neurointerventional procedures that
      leads to stroke. Stroke rates related to aneurysm coiling range from 2 to 10% and
      may be higher when considering silent ischemia. Stroke associated with carotid
      stenting is a major cause of morbidity. Antiplatelet use in the periprocedure
      setting varies among different centers. No guidelines exist for use of
      antiplatelet regimens in neurointerventional procedures. Incidence of stroke in
      patients post procedure may be partly explained by resistance to antiplatelet
      agents. Further research is required to establish the incidence of stroke in
      patients with antiplatelet resistance undergoing neurointerventional procedures.

PMID- 22363313
TI  - Patient-tailored connectomics visualization for the assessment of white matter
      atrophy in traumatic brain injury.
AB  - Available approaches to the investigation of traumatic brain injury (TBI) are
      frequently hampered, to some extent, by the unsatisfactory abilities of existing
      methodologies to efficiently define and represent affected structural
      connectivity and functional mechanisms underlying TBI-related pathology. In this
      paper, we describe a patient-tailored framework which allows mapping and
      characterization of TBI-related structural damage to the brain via multimodal
      neuroimaging and personalized connectomics. Specifically, we introduce a
      graphically driven approach for the assessment of trauma-related atrophy of white
      matter connections between cortical structures, with relevance to the
      quantification of TBI chronic case evolution. This approach allows one to inform
      the formulation of graphical neurophysiological and neuropsychological TBI
      profiles based on the particular structural deficits of the affected patient. In
      addition, it allows one to relate the findings supplied by our workflow to the
      existing body of research that focuses on the functional roles of the cortical
      structures being targeted. A graphical means for representing patient TBI status
      is relevant to the emerging field of personalized medicine and to the
      investigation of neural atrophy.

PMID- 22363314
TI  - LRRK2 in Transcription and Translation Regulation: Relevance for Parkinson's
      Disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      and is characterized by the selective loss of dopaminergic neurons and the
      presence of Lewy bodies. Mutations in the leucine-rich repeat kinase 2 (LRRK2)
      gene are the most frequent cause of both familial and sporadic PD. One critical
      question is how PD-associated LRRK2 mutations cause neurodegeneration. Here, we
      discuss recent findings related to LRRK2-mediated regulation of gene expression
      and translation and provide a critical assessment of the current models that are
      used to address the impact of LRRK2 on the transcriptome. A better understanding
      of these mechanisms could provide important new clues into the function of LRRK2
      during both normal and pathological conditions.

PMID- 22363315
TI  - Primary CNS teratocarcinoma.
AB  - Primary central nervous system (CNS) teratomas are rare tumors that consist of
      all three germ cell layers. We describe a young man with a primary malignant CNS
      teratocarcinoma presenting as leptomeningeal carcinomatosis. Diagnosis of primary
      CNS teratocarcinomas is challenging; relentless pursuit of the diagnosis must
      follow even if early ancillary studies are inconclusive.

PMID- 22363317
TI  - The modified ampullar approach for vestibular implant surgery: feasibility and
      its first application in a human with a long-term vestibular loss.
AB  - OBJECTIVE: To assess, for the first time in a human with a long-term vestibular
      loss, a modified approach to the ampullae and the feasibility of evoking a VOR by
      ampullar stimulation. MATERIALS AND METHODS: Peroperative stimulation of the
      ampullae, using the ampullar approach, was performed under full anesthesia during
      cochlear implantation in a 21-year-old female patient, who had experienced
      bilateral vestibular areflexia and sensorineural hearing loss for almost 20
      years. RESULTS: The modified ampullar approach was performed successfully with as
      minimally invasive surgery as possible. Ampullar stimulation evoked eye movements
      containing vectors congruent with the stimulated canal. As expected, the
      preliminary electrophysiological data were influenced by the general anesthesia,
      which resulted in current spread and reduced maximum amplitudes of eye movement.
      Nevertheless, they confirm the feasibility of ampullar stimulation. CONCLUSION:
      The modified ampullar approach provides safe access to the ampullae using as
      minimally invasive surgery as possible. For the first time in a human with long
      term bilateral vestibular areflexia, it is shown that the VOR can be evoked by
      ampullar stimulation, even when there has been no vestibular function for almost
      20 years. This approach should be considered in vestibular surgery, as it
      provides safe access to one of the most favorable stimulus locations for
      development of a vestibular implant.

PMID- 22363316
TI  - Basic Concepts in Understanding Recovery of Function in Vestibular Reflex
      Networks during Vestibular Compensation.
AB  - Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and
      postural deficits with the symptoms at rest, the static symptoms, partially or
      completely normalizing shortly after the lesion due to a process known as
      vestibular compensation. The symptoms are thought to result from changes in the
      activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be
      intact for recovery to occur, many investigations have focused on studying these
      neurons after lesions. At present, the neuronal plasticity underlying early
      recovery from the static symptoms is not fully understood. Here we propose that
      knowledge of the reflex identity and input-output connections of the recorded
      neurons is essential to link the responses to animal behavior. We further propose
      that the cellular mechanisms underlying vestibular compensation can be sorted out
      by characterizing the synaptic responses and time course for change in
      morphologically defined subsets of vestibular reflex projection neurons.
      Accordingly, this review focuses on the perspective gained by performing
      electrophysiological and immunolabeling studies on a specific subset of
      morphologically defined, glutamatergic vestibular reflex projection neurons, the
      principal cells of the chick tangential nucleus. Reference is made to pertinent
      findings from other studies on vestibular nuclei neurons, but no comprehensive
      review of the literature is intended since broad reviews already exist. From
      recording excitatory and inhibitory spontaneous synaptic activity in principal
      cells, we find that the rebalancing of excitatory synaptic drive bilaterally is
      essential for vestibular compensation to proceed. This work is important for it
      defines for the first time the excitatory and inhibitory nature of the changing
      synaptic inputs and the time course for changes in a morphologically defined
      subset of vestibular reflex projection neurons during early stages of vestibular
      compensation.

PMID- 22363319
TI  - Deep Brain Stimulation of the Pallidum is Effective and Might Stabilize Striatal
      D(2) Receptor Binding in Myoclonus-Dystonia.
AB  - PURPOSE: To assess clinical efficacy of deep brain stimulation (DBS) of the
      pallidum in Myoclonus-Dystonia (M-D) patients, and to compare pre- and post
      operative striatal dopamine D2 receptor availability. METHODS: Clinical
      parameters were scored using validated rating scales for myoclonus and dystonia.
      Dopamine D2 receptor binding of three patients was studied before surgery and
      approximately 2 years post-operatively using 123-I-iodobenzamide Single Photon
      Emission Computed Tomography. Two patients who did not undergo surgery served as
      controls. RESULTS: Clinically, the three M-D patients improved 83, 17, and 100%,
      respectively on the myoclonus rating scale and 78, 23, and 65% on the dystonia
      rating scale after DBS. Dopamine D2 receptor binding did not change after
      surgery. In the two control subjects, binding has lowered further. CONCLUSION:
      These findings confirm that DBS of the pallidum has beneficial effects on motor
      symptoms in M-D and suggest this procedure might stabilize dopamine D2 receptor
      binding.

PMID- 22363318
TI  - A Moderate Increase of Physiological CO(2) in a Critical Range during Stable NREM
      Sleep Episode: A Potential Gateway to REM Sleep.
AB  - Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement
      (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain,
      posterior hypothalamus and brainstem, and NREM sleep-related neurons in the
      anterior-hypothalamic area inhibit each other, thus alternating sleep
      wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit
      each other for REM sleep modulation. It has been proposed that inhibition of
      locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but
      it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset.
      The frequency of breathing pattern remains high during wake, slows down during
      NREM sleep but further escalates during REM sleep. As a result, brain CO(2) level
      increases during NREM sleep, which may alter REM sleep manifestation. It has been
      reported that hypocapnia decreases REM sleep while hypercapnia increases REM
      sleep periods. The groups of brainstem chemosensory neurons, including those
      present in LC, sense the alteration in CO(2) level and respond accordingly. For
      example, one group of LC neurons depolarize while other hyperpolarize during
      hypercapnia. In another group, hypercapnia initially depolarizes but later
      hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are
      an integral part of REM sleep executive machinery. We reason that increased CO(2)
      level during a stable NREM sleep period may hyperpolarize LC neurons including
      REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act
      as a sentinel to help maintain normal CO(2) level for unperturbed sleep.

PMID- 22363320
TI  - Cell tropism and pathogenesis of measles virus in monkeys.
AB  - Measles virus (MV) is an enveloped negative strand RNA virus belonging to the
      family of Paramyxoviridae, genus Morbillivirus, and causes one of the most
      contagious diseases in humans. Experimentally infected non-human primates are
      used as animal models for studies of the pathogenesis of human measles. We
      established a reverse genetics system based on a highly pathogenic wild-type MV.
      Infection of monkeys with recombinant MV strains generated by reverse genetics
      enabled analysis of the molecular basis of MV pathogenesis. The essential in vivo
      function of accessory genes was indicated by infecting monkeys with recombinant
      MV strains deficient in the expression of accessory genes. Furthermore,
      recombinant wild-type MV strains expressing enhanced green fluorescent protein
      enabled visual tracking of MV-infected cells in vitro and in vivo. To date, three
      different molecules have been identified as receptors for MV. Signaling
      lymphocyte activation molecule (SLAM, also called CD150), expressed on immune
      cells, is a major receptor for MV. CD46, ubiquitously expressed in all nucleated
      cells in humans and monkeys, is a receptor for vaccine and laboratory-adapted
      strains of MV. The newly identified nectin-4 (also called poliovirus-receptor
      like-4) is an epithelial cell receptor for MV. However, recent findings have
      indicated that CD46 acts as an MV receptor in vitro but not in vivo. The impact
      of the receptor usage of MV in vivo on the disease outcome is now under
      investigation.

PMID- 22363321
TI  - Assessing the probability of detection of horizontal gene transfer events in
      bacterial populations.
AB  - Experimental approaches to identify horizontal gene transfer (HGT) events of non
      mobile DNA in bacteria have typically relied on detection of the initial
      transformants or their immediate offspring. However, rare HGT events occurring in
      large and structured populations are unlikely to be detected in a short time
      frame. Population genetic modeling of the growth dynamics of bacterial genotypes
      is therefore necessary to account for natural selection and genetic drift during
      the time lag and to predict realistic time frames for detection with a given
      sampling design. Here we draw on statistical approaches to population genetic
      theory to construct a cohesive probabilistic framework for investigation of HGT
      of exogenous DNA into bacteria. In particular, the stochastic timing of rare HGT
      events is accounted for. Integrating over all possible event timings, we provide
      an equation for the probability of detection, given that HGT actually occurred.
      Furthermore, we identify the key variables determining the probability of
      detecting HGT events in four different case scenarios that are representative of
      bacterial populations in various environments. Our theoretical analysis provides
      insight into the temporal aspects of dissemination of genetic material, such as
      antibiotic resistance genes or transgenes present in genetically modified
      organisms. Due to the long time scales involved and the exponential growth of
      bacteria with differing fitness, quantitative analyses incorporating bacterial
      generation time, and levels of selection, such as the one presented here, will be
      a necessary component of any future experimental design and analysis of HGT as it
      occurs in natural settings.

PMID- 22363322
TI  - Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe
      neurological diseases.
AB  - Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and
      mouth disease (HFMD). Infection with EV71 is occasionally associated with severe
      neurological diseases such as acute encephalitis, acute flaccid paralysis, and
      cardiopulmonary failure. Because cellular receptors for viruses play an important
      role in cell, tissue, and species tropism, it is important to identify and
      characterize the receptor molecule. Recently, cellular receptors and host factors
      that stimulate EV71 infection have been identified. Several lines of evidence
      suggest that scavenger receptor class B, member 2 (SCARB2) plays critical roles
      in efficient EV71 infection and the development of disease in humans. In this
      review, we will summarize the findings of recent studies on EV71 infection and on
      the roles of SCARB2.

PMID- 22363324
TI  - Effects of nitrogen load on the function and diversity of methanotrophs in the
      littoral wetland of a boreal lake.
AB  - Methane is the second most abundant greenhouse gas in the atmosphere. A major
      part of the total methane emissions from lake ecosystems is emitted from littoral
      wetlands. Methane emissions are significantly reduced by methanotrophs, as they
      use methane as their sole energy and carbon source. Methanotrophic activity can
      be either activated or inhibited by nitrogen. However, the effects of nitrogen on
      methanotrophs in littoral wetlands are unknown. Here we report how nitrogen
      loading in situ affected the function and diversity of methanotrophs in a boreal
      littoral wetland. Methanotrophic community composition and functional diversity
      were analyzed with a particulate methane monooxygenase (pmoA) gene targeted
      microarray. Nitrogen load had no effects on methane oxidation potential and
      methane fluxes. Nitrogen load activated pmoA gene transcription of type I
      (Methylobacter, Methylomonas, and LW21-freshwater phylotypes) methanotrophs, but
      decreased the relative abundance of type II (Methylocystis, Methylosinus
      trichosporium, and Methylosinus phylotypes) methanotrophs. Hence, the overall
      activity of a methanotroph community in littoral wetlands is not affected by
      nitrogen leached from the catchment area.

PMID- 22363323
TI  - Filovirus tropism: cellular molecules for viral entry.
AB  - In human and non-human primates, filoviruses (Ebola and Marburg viruses) cause
      severe hemorrhagic fever. Recently, other animals such as pigs and some species
      of fruit bats have also been shown to be susceptible to these viruses. While
      having a preference for some cell types such as hepatocytes, endothelial cells,
      dendritic cells, monocytes, and macrophages, filoviruses are known to be
      pantropic in infection of primates. The envelope glycoprotein (GP) is responsible
      for both receptor binding and fusion of the virus envelope with the host cell
      membrane. It has been demonstrated that filovirus GP interacts with multiple
      molecules for entry into host cells, whereas none of the cellular molecules so
      far identified as a receptor/co-receptor fully explains filovirus tissue tropism
      and host range. Available data suggest that the mucin-like region (MLR) on GP
      plays an important role in attachment to the preferred target cells, whose
      infection is likely involved in filovirus pathogenesis, whereas the MLR is not
      essential for the fundamental function of the GP in viral entry into cells in
      vitro. Further studies elucidating the mechanisms of cellular entry of
      filoviruses may shed light on the development of strategies for prophylaxis and
      treatment of Ebola and Marburg hemorrhagic fevers.

PMID- 22363325
TI  - Distribution, abundance, and diversity patterns of the thermoacidophilic "deep
      sea hydrothermal vent euryarchaeota 2".
AB  - Cultivation-independent studies have shown that taxa belonging to the "deep-sea
      hydrothermal vent euryarchaeota 2" (DHVE2) lineage are widespread at deep-sea
      hydrothermal vents. While this lineage appears to be a common and important
      member of the microbial community at vent environments, relatively little is
      known about their overall distribution and phylogenetic diversity. In this study,
      we examined the distribution, relative abundance, co-occurrence patterns, and
      phylogenetic diversity of cultivable thermoacidophilic DHVE2 in deposits from
      globally distributed vent fields. Results of quantitative polymerase chain
      reaction assays with primers specific for the DHVE2 and Archaea demonstrate the
      ubiquity of the DHVE2 at deep-sea vents and suggest that they are significant
      members of the archaeal communities of established vent deposit communities.
      Local similarity analysis of pyrosequencing data revealed that the distribution
      of the DHVE2 was positively correlated with 10 other Euryarchaeota phylotypes and
      negatively correlated with mostly Crenarchaeota phylotypes. Targeted cultivation
      efforts resulted in the isolation of 12 axenic strains from six different vent
      fields, expanding the cultivable diversity of this lineage to vents along the
      East Pacific Rise and Mid-Atlantic Ridge. Eleven of these isolates shared greater
      than 97% 16S rRNA gene sequence similarity with one another and the only
      described isolate of the DHVE2, Aciduliprofundum boonei T469(T). Sequencing and
      phylogenetic analysis of five protein-coding loci, atpA, EF-2, radA, rpoB, and
      secY, revealed clustering of isolates according to geographic region of
      isolation. Overall, this study increases our understanding of the distribution,
      abundance, and phylogenetic diversity of the DHVE2.

PMID- 22363326
TI  - Tracing lifestyle adaptation in prokaryotic genomes.
AB  - Lifestyle adaptation of microbes due to changes in their ecological niches or
      acquisition of new environments is a major driving force for genetic changes in
      their respective genomes. Moving into more specialized niches often results in
      the acquisition of new gene sets via horizontal gene transfer to utilize
      previously unavailable metabolites, while genetic ballast is shed by gene loss
      and/or gene inactivation. In some cases, larger genome rearrangements can be
      observed, such as the incorporation of whole genetic islands, providing a range
      of new phenotypic capabilities. Until recently these changes could not be
      comprehensively followed and identified due to the lack of complete microbial
      genome sequences. The advent of high-throughput DNA sequencing has dramatically
      changed the scientific landscape and today microbial genomes have become
      increasingly abundant. Currently, more than 2,900 genomes are published and more
      than 11,000 genome projects are listed in the Genomes Online Database. Although
      this wealth of information provides many new opportunities to assess microbial
      functionality, it also creates a new array of challenges when a comparison
      between multiple microbial genomes is required. Here, functional genome
      distribution (FGD) is introduced, analyzing the diversity between microbes based
      on their predicted ORFeome. FGD is therefore a comparative genomics approach,
      emphasizing the assessments of gene complements. To further facilitate the
      comparison between two or more genomes, degrees of amino-acid similarities
      between ORFeomes can be visualized in the Artemis comparison tool, graphically
      depicting small and large scale genome rearrangements, insertion and deletion
      events, and levels of similarity between individual open reading frames. FGD
      provides a new tool for comparative microbial genomics and the interpretation of
      differences in the genetic makeup of bacteria.

PMID- 22363327
TI  - Characterization of Microbial Population Shifts during Sample Storage.
AB  - The objective of this study was to determine shifts in the microbial community
      structure and potential function based on standard Integrated Ocean Drilling
      Program (IODP) storage procedures for sediment cores. Standard long-term storage
      protocols maintain sediment temperature at 4 degrees C for mineralogy,
      geochemical, and/or geotechnical analysis whereas standard microbiological
      sampling immediately preserves sediments at -80 degrees C. Storage at 4 degrees C
      does not take into account populations may remain active over geologic time
      scales at temperatures similar to storage conditions. Identification of active
      populations within the stored core would suggest geochemical and geophysical
      conditions within the core change over time. To test this potential, the
      metabolically active fraction of the total microbial community was characterized
      from IODP Expedition 325 Great Barrier Reef sediment cores prior to and following
      a 3-month storage period. Total RNA was extracted from complementary 2, 20, and
      40 m below sea floor sediment samples, reverse transcribed to complementary DNA
      and then sequenced using 454 FLX sequencing technology, yielding over 14,800
      sequences from the six samples. Interestingly, 97.3% of the sequences detected
      were associated with lineages that changed in detection frequency during the
      storage period including key biogeochemically relevant lineages associated with
      nitrogen, iron, and sulfur cycling. These lineages have the potential to
      permanently alter the physical and chemical characteristics of the sediment
      promoting misleading conclusions about the in situ biogeochemical environment. In
      addition, the detection of new lineages after storage increases the potential for
      a wider range of viable lineages within the subsurface that may be underestimated
      during standard community characterizations.

PMID- 22363328
TI  - Molecular Underpinnings of Fe(III) Oxide Reduction by Shewanella Oneidensis MR-1.
AB  - In the absence of O(2) and other electron acceptors, the Gram-negative bacterium
      Shewanella oneidensis MR-1 can use ferric [Fe(III)] (oxy)(hydr)oxide minerals as
      the terminal electron acceptors for anaerobic respiration. At circumneutral pH
      and in the absence of strong complexing ligands, Fe(III) oxides are relatively
      insoluble and thus are external to the bacterial cells. S. oneidensis MR-1 and
      related strains of metal-reducing Shewanella have evolved machinery (i.e., metal
      reducing or Mtr pathway) for transferring electrons from the inner-membrane,
      through the periplasm and across the outer-membrane to the surface of
      extracellular Fe(III) oxides. The protein components identified to date for the
      Mtr pathway include CymA, MtrA, MtrB, MtrC, and OmcA. CymA is an inner-membrane
      tetraheme c-type cytochrome (c-Cyt) that belongs to the NapC/NrfH family of
      quinol dehydrogenases. It is proposed that CymA oxidizes the quinol in the inner
      membrane and transfers the released electrons to MtrA either directly or
      indirectly through other periplasmic proteins. A decaheme c-Cyt, MtrA is thought
      to be embedded in the trans outer-membrane and porin-like protein MtrB. Together,
      MtrAB deliver the electrons through the outer-membrane to the MtrC and OmcA on
      the outmost bacterial surface. MtrC and OmcA are the outer-membrane decaheme c
      Cyts that are translocated across the outer-membrane by the bacterial type II
      secretion system. Functioning as terminal reductases, MtrC and OmcA can bind the
      surface of Fe(III) oxides and transfer electrons directly to these minerals via
      their solvent-exposed hemes. To increase their reaction rates, MtrC and OmcA can
      use the flavins secreted by S. oneidensis MR-1 cells as diffusible co-factors for
      reduction of Fe(III) oxides. Because of their extracellular location and broad
      redox potentials, MtrC and OmcA can also serve as the terminal reductases for
      soluble forms of Fe(III). In addition to Fe(III) oxides, Mtr pathway is also
      involved in reduction of manganese oxides and other metals. Although our
      understanding of the Mtr pathway is still far from complete, it is the best
      characterized microbial pathway used for extracellular electron exchange.
      Characterizations of the Mtr pathway have made significant contributions to the
      molecular understanding of microbial reduction of Fe(III) oxides.

PMID- 22363330
TI  - Reconstruction of Extracellular Respiratory Pathways for Iron(III) Reduction in
      Shewanella Oneidensis Strain MR-1.
AB  - Shewanella oneidensis strain MR-1 is a facultative anaerobic bacterium capable of
      respiring a multitude of electron acceptors, many of which require the Mtr
      respiratory pathway. The core Mtr respiratory pathway includes a periplasmic c
      type cytochrome (MtrA), an integral outer-membrane beta-barrel protein (MtrB),
      and an outer-membrane-anchored c-type cytochrome (MtrC). Together, these
      components facilitate transfer of electrons from the c-type cytochrome CymA in
      the cytoplasmic membrane to electron acceptors at and beyond the outer-membrane.
      The genes encoding these core proteins have paralogs in the S. oneidensis genome
      (mtrB and mtrA each have four while mtrC has three) and some of the paralogs of
      mtrC and mtrA are able to form functional Mtr complexes. We demonstrate that of
      the additional three mtrB paralogs found in the S. oneidensis genome, only MtrE
      can replace MtrB to form a functional respiratory pathway to soluble iron(III)
      citrate. We also evaluate which mtrC/mtrA paralog pairs (a total of 12
      combinations) are able to form functional complexes with endogenous levels of
      mtrB paralog expression. Finally, we reconstruct all possible functional Mtr
      complexes and test them in a S. oneidensis mutant strain where all paralogs have
      been eliminated from the genome. We find that each combination tested with the
      exception of MtrA/MtrE/OmcA is able to reduce iron(III) citrate at a level
      significantly above background. The results presented here have implications
      toward the evolution of anaerobic extracellular respiration in Shewanella and for
      future studies looking to increase the rates of substrate reduction for water
      treatment, bioremediation, or electricity production.

PMID- 22363329
TI  - Role of the HIV-1 Matrix Protein in Gag Intracellular Trafficking and Targeting
      to the Plasma Membrane for Virus Assembly.
AB  - Human immunodeficiency virus type-1 (HIV-1) encodes a polypeptide called Gag that
      is able to form virus-like particles in vitro in the absence of any cellular or
      viral constituents. During the late phase of the HIV-1 infection, Gag
      polyproteins are transported to the plasma membrane (PM) for assembly. In the
      past two decades, in vivo, in vitro, and structural studies have shown that Gag
      trafficking and targeting to the PM are orchestrated events that are dependent on
      multiple factors including cellular proteins and specific membrane lipids. The
      matrix (MA) domain of Gag has been the focus of these studies as it appears to be
      engaged in multiple intracellular interactions that are suggested to be critical
      for virus assembly and replication. The interaction between Gag and the PM is
      perhaps the most understood. It is now established that the ultimate localization
      of Gag on punctate sites on the PM is mediated by specific interactions between
      the MA domain of Gag and phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)], a
      minor lipid localized on the inner leaflet of the PM. Structure-based studies
      revealed that binding of PI(4,5)P(2) to MA induces minor conformational changes,
      leading to exposure of the myristyl (myr) group. Exposure of the myr group is
      also triggered by binding of calmodulin, enhanced by factors that promote protein
      self-association like the capsid domain of Gag, and is modulated by pH. Despite
      the steady progress in defining both the viral and cellular determinants of
      retroviral assembly and release, Gag's intracellular interactions and trafficking
      to its assembly sites in the infected cell are poorly understood. In this review,
      we summarize the current understanding of the structural and functional role of
      MA in HIV replication.

PMID- 22363331
TI  - Toward a mechanistic understanding of anaerobic nitrate-dependent iron oxidation:
      balancing electron uptake and detoxification.
AB  - The anaerobic oxidation of Fe(II) by subsurface microorganisms is an important
      part of biogeochemical cycling in the environment, but the biochemical mechanisms
      used to couple iron oxidation to nitrate respiration are not well understood.
      Based on our own work and the evidence available in the literature, we propose a
      mechanistic model for anaerobic nitrate-dependent iron oxidation. We suggest that
      anaerobic iron-oxidizing microorganisms likely exist along a continuum including:
      (1) bacteria that inadvertently oxidize Fe(II) by abiotic or biotic reactions
      with enzymes or chemical intermediates in their metabolic pathways (e.g.,
      denitrification) and suffer from toxicity or energetic penalty, (2) Fe(II)
      tolerant bacteria that gain little or no growth benefit from iron oxidation but
      can manage the toxic reactions, and (3) bacteria that efficiently accept
      electrons from Fe(II) to gain a growth advantage while preventing or mitigating
      the toxic reactions. Predictions of the proposed model are highlighted and
      experimental approaches are discussed.

PMID- 22363332
TI  - The Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein and Its Multiple Roles
      in mRNA Biogenesis.
AB  - Post-transcriptional events which regulate mRNA biogenesis are fundamental to the
      control of gene expression. A nascent mRNA is therefore steered through
      multimeric RNA-protein complexes that mediate its capping, splicing,
      polyadenylation, nuclear export, and ultimately its translation. Kaposi's sarcoma
      associated herpesvirus (KSHV) mRNA transport and accumulation protein, or ORF57,
      is a functionally conserved protein found in all herpesviruses which plays a
      pivotal role in enhancing viral gene expression at a post-transcriptional level.
      As such, ORF57 has been implicated in multiple steps of RNA biogenesis, including
      augmenting viral splicing, protecting viral RNAs from degradation to enhancing
      viral mRNA nuclear export and translation. In this review, we highlight the
      multiple roles of KSHV ORF57 in regulating the post-transcriptional events which
      are fundamental to the control of virus gene expression.

PMID- 22363334
TI  - Resident Cats in Small Animal Veterinary Hospitals Carry Multi-Drug Resistant
      Enterococci and are Likely Involved in Cross-Contamination of the Hospital
      Environment.
AB  - In the USA, small animal veterinary hospitals (SAVHs) commonly keep resident cats
      living permanently as pets within their facilities. Previously, multi-drug
      resistant (MDR) enterococci were found as a contaminant of multiple surfaces
      within such veterinary hospitals, and nosocomial infections are a concern. The
      objectives of this study were to determine whether resident cats carry MDR
      enterococci and to compare the feline isolates genotypically to those obtained
      from SAVH surfaces in a previous study. Enterococcal strains (n = 180) were
      isolated from the feces of six healthy resident cats from different SAVHs. The
      concentration of enterococci ranged from 1.1 * 10(5) to 6.0 * 10(8) CFU g(-1) of
      feces, and the population comprised Enterococcus hirae (38.3 +/- 18.6%), E.
      faecium (35.0 +/- 14.3%), E. faecalis (23.9 +/- 11.0%), and E. avium (2.8 +/-
      2.2%). Testing of phenotypic resistance to 14 antimicrobial agents revealed multi
      drug resistance (>=3 antimicrobials) in 48.9% of all enterococcal isolates with
      most frequent resistance to tetracycline (75.0%), erythromycin (50.0%), and
      rifampicin (36.1%). Vancomycin resistant E. faecalis (3.9%) with vanB not
      horizontally transferable in in vitro conjugation assays were detected from one
      cat. Genotyping with pulsed-field gel electrophoresis demonstrated a host
      specific clonal population of MDR E. faecalis and E. faecium. Importantly,
      several feline isolates were genotypically identical or closely related to
      isolates from surfaces of cage door, thermometer, and stethoscope of the
      corresponding SAVHs. These data demonstrate that healthy resident cats at SAVHs
      carry MDR enterococci and likely contribute to contamination of the SAVH
      environment. Proper disposal and handling of fecal material and restricted
      movement of resident cats within the ward are recommended.

PMID- 22363335
TI  - Stable carbon isotope fractionation in chlorinated ethene degradation by bacteria
      expressing three toluene oxygenases.
AB  - One difficulty in using bioremediation at a contaminated site is demonstrating
      that biodegradation is actually occurring in situ. The stable isotope composition
      of contaminants may help with this, since they can serve as an indicator of
      biological activity. To use this approach it is necessary to establish how a
      particular biodegradation pathway affects the isotopic composition of a
      contaminant. This study examined bacterial strains expressing three aerobic
      enzymes for their effect on the (13)C/(12)C ratio when degrading both
      trichloroethene (TCE) and cis-1,2-dichloroethene (c-DCE): toluene 3-monoxygenase,
      toluene 4-monooxygenase, and toluene 2,3-dioxygenase. We found no significant
      differences in fractionation among the three enzymes for either compound. Aerobic
      degradation of c-DCE occurred with low fractionation producing delta(13)C
      enrichment factors of -0.9 +/- 0.5 to -1.2 +/- 0.5, in contrast to reported
      anaerobic degradation delta(13)C enrichment factors of -14.1 to -20.40/00.
      Aerobic degradation of TCE resulted in delta(13)C enrichment factors of -11.6 +/-
      4.1 to -14.7 +/- 3.00/00 which overlap reported delta(13)C enrichment factors for
      anaerobic TCE degradation of -2.5 to -13.80/00. The data from this study suggest
      that stable isotopes could serve as a diagnostic for detecting aerobic
      biodegradation of TCE by toluene oxygenases at contaminated sites.

PMID- 22363333
TI  - Trace metal requirements for microbial enzymes involved in the production and
      consumption of methane and nitrous oxide.
AB  - Fluxes of greenhouse gases to the atmosphere are heavily influenced by
      microbiological activity. Microbial enzymes involved in the production and
      consumption of greenhouse gases often contain metal cofactors. While extensive
      research has examined the influence of Fe bioavailability on microbial CO(2)
      cycling, fewer studies have explored metal requirements for microbial production
      and consumption of the second- and third-most abundant greenhouse gases, methane
      (CH(4)), and nitrous oxide (N(2)O). Here we review the current state of
      biochemical, physiological, and environmental research on transition metal
      requirements for microbial CH(4) and N(2)O cycling. Methanogenic archaea require
      large amounts of Fe, Ni, and Co (and some Mo/W and Zn). Low bioavailability of
      Fe, Ni, and Co limits methanogenesis in pure and mixed cultures and environmental
      studies. Anaerobic methane oxidation by anaerobic methanotrophic archaea (ANME)
      likely occurs via reverse methanogenesis since ANME possess most of the enzymes
      in the methanogenic pathway. Aerobic CH(4) oxidation uses Cu or Fe for the first
      step depending on Cu availability, and additional Fe, Cu, and Mo for later steps.
      N(2)O production via classical anaerobic denitrification is primarily Fe-based,
      whereas aerobic pathways (nitrifier denitrification and archaeal ammonia
      oxidation) require Cu in addition to, or possibly in place of, Fe. Genes encoding
      the Cu-containing N(2)O reductase, the only known enzyme capable of microbial
      N(2)O conversion to N(2), have only been found in classical denitrifiers.
      Accumulation of N(2)O due to low Cu has been observed in pure cultures and a lake
      ecosystem, but not in marine systems. Future research is needed on metalloenzymes
      involved in the production of N(2)O by enrichment cultures of ammonia oxidizing
      archaea, biological mechanisms for scavenging scarce metals, and possible links
      between metal bioavailability and greenhouse gas fluxes in anaerobic environments
      where metals may be limiting due to sulfide-metal scavenging.

PMID- 22363336
TI  - Isolation of sulfate-reducing bacteria from sediments above the deep-subseafloor
      aquifer.
AB  - On a global scale, crustal fluids fuel a large part of the deep-subseafloor
      biosphere by providing electron acceptors for microbial respiration. In this
      study, we examined bacterial cultures from sediments of the Juan de Fuca Ridge,
      Northeast Pacific (IODP Site U1301). The sediments comprise three distinctive
      compartments: an upper sulfate-containing zone, formed by bottom-seawater
      diffusion, a sulfate-depleted zone, and a second (~140 m thick) sulfate
      containing zone influenced by fluid diffusion from the basaltic aquifer. In order
      to identify and characterize sulfate-reducing bacteria, enrichment cultures from
      different sediment layers were set up, analyzed by molecular screening, and used
      for isolating pure cultures. The initial enrichments harbored specific
      communities of heterotrophic microorganisms. Strains affiliated to
      Desulfosporosinus lacus, Desulfotomaculum sp., and Desulfovibrio aespoeensis were
      isolated only from the top layers (1.3-9.1 meters below seafloor, mbsf), while
      several strains of Desulfovibrio indonesiensis and a relative of Desulfotignum
      balticum were obtained from near-basement sediments (240-262 mbsf). Physiological
      tests on three selected strains affiliated to Dv. aespoeensis, Dv. indonesiensis,
      and Desulfotignum balticum indicated that all reduce sulfate with a limited
      number of short-chain n-alcohols or fatty acids and were able to ferment either
      ethanol, pyruvate, or betaine. All three isolates shared the capacity of growing
      chemolithotrophically with H(2) as sole electron donor. Strain P23, affiliating
      with Dv. indonesiensis, even grew autotrophically in the absence of any organic
      compounds. Thus, H(2) might be an essential electron donor in the deep
      subseafloor where the availability of organic substrates is limited. The
      isolation of non-sporeforming sulfate reducers from fluid-influenced layers
      indicates that they have survived the long-term burial as active populations even
      after the separation from the seafloor hundreds of meters above.

PMID- 22363337
TI  - Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment
      and antibiotic resistance in indochina.
AB  - Southeast Asia has become the center of rapid industrial development and economic
      growth. However, this growth has far outpaced investment in public
      infrastructure, leading to the unregulated release of many pollutants, including
      wastewater-related contaminants such as antibiotics. Antibiotics are of major
      concern because they can easily be released into the environment from numerous
      sources, and can subsequently induce development of antibiotic-resistant
      bacteria. Recent studies have shown that for some categories of drugs this source
      to-environment antibiotic resistance relationship is more complex. This review
      summarizes current understanding regarding the presence of quinolones,
      sulfonamides, and tetracyclines in aquatic environments of Indochina and the
      prevalence of bacteria resistant to them. Several noteworthy findings are
      discussed: (1) quinolone contamination and the occurrence of quinolone resistance
      are not correlated; (2) occurrence of the sul sulfonamide resistance gene varies
      geographically; and (3) microbial diversity might be related to the rate of
      oxytetracycline resistance.

PMID- 22363338
TI  - T Cell Adaptive Immunity Proceeds through Environment-Induced Adaptation from the
      Exposure of Cryptic Genetic Variation.
AB  - Evolution is often characterized as a process involving incremental genetic
      changes that are slowly discovered and fixed in a population through genetic
      drift and selection. However, a growing body of evidence is finding that changes
      in the environment frequently induce adaptations that are much too rapid to occur
      by an incremental genetic search process. Rapid evolution is hypothesized to be
      facilitated by mutations present within the population that are silent or
      "cryptic" within the first environment but are co-opted or "exapted" to the new
      environment, providing a selective advantage once revealed. Although cryptic
      mutations have recently been shown to facilitate evolution in RNA enzymes, their
      role in the evolution of complex phenotypes has not been proven. In support of
      this wider role, this paper describes an unambiguous relationship between cryptic
      genetic variation and complex phenotypic responses within the immune system. By
      reviewing the biology of the adaptive immune system through the lens of
      evolution, we show that T cell adaptive immunity constitutes an exemplary model
      system where cryptic alleles drive rapid adaptation of complex traits. In naive T
      cells, normally cryptic differences in T cell receptor reveal diversity in
      activation responses when the cellular population is presented with a novel
      environment during infection. We summarize how the adaptive immune response
      presents a well studied and appropriate experimental system that can be used to
      confirm and expand upon theoretical evolutionary models describing how seemingly
      small and innocuous mutations can drive rapid cellular evolution.

PMID- 22363339
TI  - A cross-platform genome-wide comparison of the relationship of promoter DNA
      methylation to gene expression.
AB  - Peripheral mononuclear cell preparations are commonly used as proxies for other
      tissues in studies of the role of gene expression and methylation in human
      disease. Whether changes in peripheral DNA methylation are associated with
      changes in peripheral blood or brain gene expression is not clear. In order to
      test the former hypothesis and determine which genome-wide methylation platform
      was most suitable for our studies of peripheral blood cells, we compared the
      results from two commercially available genome-wide methylation arrays with
      respect to genome-wide gene expression using lymphoblast DNA and RNA from eight
      individuals at the promoters of 5619 genes. We found that methylation signatures
      at these gene promoters were significantly correlated with one another across
      platforms and with genome-wide gene expression, but the extent of that
      relationship is dependent on choice of platform and degree of methylation. Taken
      in context with data from other studies, these data demonstrate that peripheral
      blood cell methylation is associated with gene expression and that further
      studies to clarify the extent of this relationship, and the relationship between
      central and peripheral DNA methylation are in order.

PMID- 22363340
TI  - Indy mutants: live long and prosper.
AB  - Indy encodes the fly homolog of a mammalian transporter of di and tricarboxylate
      components of the Krebs cycle. Reduced expression of fly Indy or two of the C.
      elegans Indy homologs leads to an increase in life span. Fly and worm tissues
      that play key roles in intermediary metabolism are also the places where Indy
      genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly
      expressed in the liver. It has been hypothesized that decreased INDY activity
      creates a state similar to caloric restriction (CR). This hypothesis is supported
      by the physiological similarities between Indy mutant flies on high calorie food
      and control flies on CR, such as increased physical activity and decreases in
      weight, egg production, triglyceride levels, starvation resistance, and insulin
      signaling. In addition, Indy mutant flies undergo changes in mitochondrial
      biogenesis also observed in CR animals. Recent findings with mIndy knockout mice
      support and extend the findings from flies. mIndy(-/-) mice display an increase
      in hepatic mitochondrial biogenesis, lipid oxidation, and decreased hepatic
      lipogenesis. When mIndy(-/-) mice are fed high calorie food they are protected
      from adiposity and insulin resistance. These findings point to INDY as a
      potential drug target for the treatment of metabolic syndrome, type 2 diabetes,
      and obesity.

PMID- 22363341
TI  - Color-pattern evolution in response to environmental stress in butterflies.
AB  - It is generally accepted that butterfly wing color-patterns have ecological and
      behavioral functions that evolved through natural selection. However, particular
      wing color-patterns may be produced physiologically in response to environmental
      stress, and they may lack significant function. These patterns would represent an
      extreme expression of phenotypic plasticity and can eventually be fixed
      genetically in a population. Here, three such cases in butterflies are concisely
      reviewed, and their possible mechanisms of genetic assimilation are discussed.
      First, a certain modified color-pattern of Vanessa indica induced by temperature
      treatments resembles the natural color-patterns of its closely related species of
      the genus Vanessa (sensu stricto). Second, a different type of color-pattern
      modification can be induced in Vanessa cardui as a result of a general stress
      response. This modified pattern is very similar to the natural color-pattern of
      its sister species Vanessa kershawi. Third, a field observation was reported,
      together with experimental support, to show that the color-pattern diversity of a
      regional population of Zizeeria maha increased at the northern range margin of
      this species in response to temperature stress. In these three cases, modified
      color-patterns are unlikely to have significant functions, and these cases
      suggest that phenotypic plasticity plays an important role in butterfly wing
      color-pattern evolution. A neutral or non-functional trait can be assimilated
      genetically if it is linked, like a parasitic trait, with another functional
      trait. In addition, it is possible that environmental stress causes epigenetic
      modifications of genes related to color-patterns and that their transgenerational
      inheritance facilitates the process of genetic assimilation of a neutral or non
      functional trait.

PMID- 22363342
TI  - A central role for long non-coding RNA in cancer.
AB  - Long non-coding RNAs (ncRNAs) have been shown to regulate important biological
      processes that support normal cellular functions. Aberrant regulation of these
      essential functions can promote tumor development. In this review, we underscore
      the importance of the regulatory role played by this distinct class of ncRNAs in
      cancer-associated pathways that govern mechanisms such as cell growth, invasion,
      and metastasis. We also highlight the possibility of using these unique RNAs as
      diagnostic and prognostic biomarkers in malignancies.

PMID- 22363343
TI  - DNA Methylation Fluctuation Induced by Virus Infection Differs between MD
      resistant and -susceptible Chickens.
AB  - Marek's disease (MD) is a lymphoproliferative disease induced by Marek's disease
      virus (MDV) infection. To augment vaccination measures in MD control, host
      genetic resistant to MD becomes obviously more and more important. To elucidate
      the mechanism of MD-resistance, most of researches were focused on the genetic
      differences between resistant and susceptible chickens. However, epigenetic
      features between MD resistant and susceptible chickens are poorly characterized.
      Using bisulfite pyrosequencing method, we found some candidate genes have higher
      promoter methylation in the MD-susceptible (L7(2)) chickens than in the MD
      resistant (L6(3)) chickens. The hypermethylated genes, involved in cellular
      component organization, responding to stimulus, cell adhesion, and immune system
      process, may play important role in susceptibility to disease by deregulation of
      these genes. MDV infection induced the expression changes of all three
      methyltransferases genes (DNMT1, DNMT3a, and DNMT3b) in both lines of chickens.
      The DNMT1 was up-regulated in L7(2), whereas the DNMT3b was down-regulated in
      L6(3) at 21 dpi. Interestingly, a dynamic change of promoter methylation was
      observed during MDV life cycle. Some genes, including HDAC9, GH, STAT1, CIITA,
      FABP3, LATS2, and H2Ac, showed differential methylation behaviors between the two
      lines of chickens. In summary, the findings from this study suggested that DNA
      methylation heterogeneity and MDV infection induced methylation alterations
      differences existed between the two lines of chickens. Therefore, it is suggested
      that epigenetic mechanisms may be involved in modulating the resistance and/or
      susceptibility to MD in chickens.

PMID- 22363344
TI  - Naturally occurring variation in trophoblast invasion as a source of novel
      (epigenetic) biomarkers.
AB  - During the first trimester of pregnancy fetal trophoblasts invade the maternal
      decidua, thereby remodeling the maternal spiral arteries. This process of
      trophoblast invasion is very similar to cancer cell invasion, with multiple
      signaling pathways shared between the two. Pregnancy-related diseases, e.g., pre
      eclampsia, and cancer metastasis start with a decrease or increase in cellular
      invasion, respectively. Here, we investigate if first trimester placental
      explants can be used to identify epigenetic factors associated with changes in
      cellular invasion and their potential use as biomarkers. We show that the
      outgrowth potential of first trimester explants significantly correlates with
      promoter methylation of PRKCDBP and MMP2, two genes known to be differentially
      methylated in both placenta and cancer. The increase in methylation percentage of
      placental cells coincides with an increase in invasion potential. Subsequently,
      as a non-invasive marker must be detectable in blood, plasma samples of pregnant
      and non-pregnant women were analyzed. The MMP2 promoter showed high methylation
      levels in non-pregnant plasma samples, which decreased in pregnant plasma samples
      which also contain placental DNA. The decrease in methylated plasma DNA during
      pregnancy is most likely due to the fractional increase in unmethylated placental
      DNA. This suggests that the level of unmethylated DNA has the potential to be
      used as an invasion marker, where higher levels of unmethylated DNA indicate a
      lower invasion potential of trophoblasts. These proof of principle data provide
      evidence that human first trimester placental explants are an excellent ex vivo
      model system to identify (epigenetic) factors and thus potential biomarkers
      associated with changes in cellular invasion, e.g., to detect pregnancy-related
      diseases or cancer metastasis. To identify novel biomarkers the next step is to
      correlate naturally occurring variation in invasion potential to changes in
      (epigenetic) factors by genome-wide approaches such as massively parallel
      sequencing.

PMID- 22363345
TI  - An Overview of the CNS-Pharmacodynamic Profiles of Nonselective and Selective
      GABA Agonists.
AB  - Various alpha(2,3) subtype selective partial GABA-A agonists are in development
      to treat anxiety disorders. These compounds are expected to be anxiolytic with
      fewer undesirable side effects, compared to nonselective GABA-A agonists like
      benzodiazepines. Several alpha(2,3) subtype selective and nonselective GABA-A
      agonists have been examined in healthy volunteers, using a battery addressing
      different brain domains. Data from five placebo-controlled double-blind studies
      were pooled. Lorazepam 2 mg was the comparator in three studies. Three alpha(2,3)
      selective GABAA agonists (i.e., TPA023, TPACMP2, SL65.1498), one alpha(1)
      selective GABAA agonists (zolpidem), and another full agonist (alprazolam) were
      examined. Pharmacological selectivity was assessed by determination of regression
      lines for the change from baseline of saccadic-peak-velocity- (DeltaSPV-)
      relative effect, relative to changes in different pharmacodynamic endpoints
      (DeltaPD). SPV was chosen for its sensitivity to the anxiolysis of
      benzodiazepines. Slopes of the DeltaSPV-DeltaPD relations were consistently lower
      with the alpha(2,3) selective GABA-A agonists than with lorazepam, indicating
      that their PD effects are less than their SPV-effects. The DeltaSPV-DeltaPD
      relations of lorazepam were comparable to alprazolam. Zolpidem showed relatively
      higher impairments in DeltaPD relative to DeltaSPV, but did not significantly
      differ from lorazepam. These PD results support the pharmacological selectivity
      of the alpha(2,3)-selective GABA-A agonists, implying an improved therapeutic
      window.

PMID- 22363346
TI  - Lung Cancer and Human Papilloma Viruses (HPVs): Examining the Molecular Evidence.
AB  - Human papilloma virus (HPV), known to be an etiological agent for genital
      cancers, has been suggested also to be a possible contributory agent for lung
      cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's
      disease, may now be more appropriately categorised into never smoker's and
      smoker's lung cancer. Through this paper we attempt to bring forth the current
      knowledge regarding mechanisms of HPV gaining access into the lung tissue,
      various strategies involved in HPV-associated tumorigenesis in lung tissue.

PMID- 22363347
TI  - New and Simple Approach for Preventing Postoperative Peritoneal Adhesions: Do not
      Touch the Peritoneum without Viscous Liquid-A Multivariate Analysis.
AB  - Background. Postoperative peritoneal adhesions (PPAs) are an unsolved and serious
      problem in abdominal surgery. Method. Viscous liquids of soybean oil, octyl
      methoxycinnamate, flax oil, aloe vera gel, and glycerol were used in five
      experiments, using the same methodology for each. Liquids were applied in the
      peritoneal cavity before and after mechanical peritoneal trauma. Results were
      evaluated by multivariate analysis. Results. Compared with the control group,
      macroscopic and microscopic adhesion values before (P < .001) and after (P < .05)
      application of viscous liquids significantly reduced PPAs. Values were
      significantly lower when liquids were applied before rather than after peritoneal
      trauma (P < .0001). Discussion. Viscous liquids injected into the peritoneal
      cavity before or after mechanical peritoneal trauma decrease PPA. Injection
      before trauma was more effective than after trauma. In surgical practice, PPA
      formation may be prevented or decreased by covering the peritoneal cavity with an
      appropriate viscous liquid before abdominal surgery.

PMID- 22363348
TI  - In vivo healing of meniscal lacerations using bone marrow-derived mesenchymal
      stem cells and fibrin glue.
AB  - Fibrin glue created from a patient's own blood can be used as a carrier to
      deliver cells to the specific site of an injury. An experimental model for
      optimizing various permutations of this delivery system in vivo was tested in
      this study. Harvested equine meniscal sections were reapposed with fibrin glue or
      fibrin glue and equine bone marrow-derived mesenchymal stem cells (BMSCs). These
      constructs were then implanted subcutaneously in nude mice. After harvesting of
      the constructs, BMSC containing constructs showed significantly increased
      vascularization, and histology showed subjectively decreased thickness of repair
      tissue and increased total bonding compared to fibrin alone constructs. This
      model allowed direct comparison of different meniscal treatment groups while
      using a small number of animals. This in vivo model could be valuable in the
      future to optimize fibrin and cellular treatments for meniscal lesions in the
      horse and potentially humans as well.

PMID- 22363349
TI  - Peptides Derived from Mycobacterium leprae ML1601c Discriminate between Leprosy
      Patients and Healthy Endemic Controls.
AB  - The stable incidence of new leprosy cases suggests that transmission of infection
      continues despite worldwide implementation of MDT. Thus, specific tools are
      needed to diagnose early stage Mycobacterium leprae infection, the likely sources
      of transmission. M. leprae antigens that induce T-cell responses in M. leprae
      exposed and/or infected individuals thus are major targets for new diagnostic
      tools. Previously, we showed that ML1601c was immunogenic in patients and healthy
      household contacts (HHC). However, some endemic controls (EC) also recognized
      this protein. To improve the diagnostic potential, IFN-gamma responses to ML1601c
      peptides were assessed using PBMC from Brazilian leprosy patients and EC. Five
      ML1601c peptides only induced IFN-gamma in patients and HHC. Moreover, 24-hour
      whole-blood assay (WBA), two ML1601c peptides could assess the level of M. leprae
      exposure in Ethiopian EC. Beside IFN-gamma, also IP-10, IL-6, IL-1beta, TNF
      alpha, and MCP-1 were increased in EC from areas with high leprosy prevalence in
      response to these ML1601c peptides. Thus, ML1601c peptides may be useful for
      differentiating M. leprae exposed or infected individuals and can also be used to
      indicate the magnitude of M. leprae transmission even in the context of various
      HLA alleles as present in these different genetic backgrounds.

PMID- 22363350
TI  - A vectorial capacity product to monitor changing malaria transmission potential
      in epidemic regions of Africa.
AB  - Rainfall and temperature are two of the major factors triggering malaria
      epidemics in warm semi-arid (desert-fringe) and high altitude (highland-fringe)
      epidemic risk areas. The ability of the mosquitoes to transmit Plasmodium spp. is
      dependent upon a series of biological features generally referred to as vectorial
      capacity. In this study, the vectorial capacity model (VCAP) was expanded to
      include the influence of rainfall and temperature variables on malaria
      transmission potential. Data from two remote sensing products were used to
      monitor rainfall and temperature and were integrated into the VCAP model. The
      expanded model was tested in Eritrea and Madagascar to check the viability of the
      approach. The analysis of VCAP in relation to rainfall, temperature and malaria
      incidence data in these regions shows that the expanded VCAP correctly tracks the
      risk of malaria both in regions where rainfall is the limiting factor and in
      regions where temperature is the limiting factor. The VCAP maps are currently
      offered as an experimental resource for testing within Malaria Early Warning
      applications in epidemic prone regions of sub-Saharan Africa. User feedback is
      currently being collected in preparation for further evaluation and refinement of
      the VCAP model.

PMID- 22363352
TI  - Effects of three types of oil dispersants on biodegradation of dispersed crude
      oil in water surrounding two Persian gulf provinces.
AB  - OBJECTIVE: To determine the most effective and biodegradable dispersant of
      spilled oil in water surrounding two Persian Gulf provinces. METHODS: This study
      compared the effects of three dispersants, Pars 1, Pars 2, and Gamlen OD4000 on
      removal of oil in two Persian Gulf provinces' water. Overall, 16 stations were
      selected. Using the Well method, the growth rate of isolated bacteria and fungi
      was identified. To specify the growth rate of microorganisms and their usage of
      oil in the presence of the above-mentioned dispersants, as exclusive sources of
      carbon, the bacteria were grown in culture medium for 28 days at 120 rpm, 30
      degrees C, and their optical density was measured by spectrophotometry. Then, we
      tested biological oxygen demand (BOD) and chemical oxygen demand (COD) in
      microorganisms. RESULTS: The highest growth rate was documented for the growth of
      microorganisms on either Pars 1 or Pars 2 dispersants or their mixtures with oil.
      However, the culture having microorganisms grown on Pars 1 had higher BOD and COD
      than the other two dispersants (9200 and 16800 versus 500 and 960, P < 0.05).
      Mixture of oil and Pars 2 as well as oil and Pars 1 dispersants showed the
      highest BODs and CODs, respectively. In the Bahregan province, microorganisms
      grown on Pars 2 had maximum amount of BOD and COD in comparison with Pars 1 and
      Gamlen dispersants (7100 and 15200 versus 6000 and 10560, P < 0.05). CONCLUSION:
      Pars 1 and Pars 2 were the most effective dispersants with highest degradability
      comparing Gamlen. In each region, the most suitable compound for removing oil
      spill from offshores with least secondary contamination should be investigated.

PMID- 22363351
TI  - Urinary bisphenol A and hypertension in a multiethnic sample of US adults.
AB  - BACKGROUND: Bisphenol A (BPA) is a common chemical used in the manufacture of
      polycarbonate plastics and epoxy resins, with >93% of US adults having detectable
      BPA levels in urine. Recent animal studies have suggested that BPA exposure may
      have a role in several mechanisms involved in the development of hypertension,
      including weight gain, insulin resistance, thyroid dysfunction, endothelial
      dysfunction, and oxidative stress. However, no previous human study has examined
      the association between markers of BPA exposure and hypertension. METHODS: We
      examined urinary BPA levels in 1380 subjects from the National Health and
      Nutritional Examination Survey 2003-2004. Main outcome-of-interest was
      hypertension, defined as blood pressure-reducing medication use and/or blood
      pressures >140/90 mm of Hg (n = 580). RESULTS: We observed a positive association
      between increasing levels of urinary BPA and hypertension independent of
      confounding factors such as age, gender, race/ethnicity, smoking, body mass index
      (BMI), diabetes mellitus and total serum cholesterol levels. Compared to tertile
      1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of
      hypertension associated with tertile 3 was 1.50 (1.12-2.00); P-trend = 0.007. The
      association was consistently present in subgroup analyses by race/ethnicity,
      smoking status, BMI, and diabetes mellitus. CONCLUSIONS: Urinary BPA levels are
      associated with hypertension, independent of traditional risk factors.

PMID- 22363353
TI  - Investigation of Transforming Growth Factor-beta1 Gene Polymorphisms Among
      Iranian Patients With Chronic Hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C infection is caused by the hepatitis C virus
      (HCV), and its clinical complications include liver cirrhosis, liver failure, and
      hepatocellular carcinoma.Transforming growth factor-beta1 (TGF-beta1) is an
      important cytokine in cell growthand differentiation, angiogenesis, extracellular
      matrix formation, immune responseregulation, and cancer development and
      progression. OBJECTIVES: The aim of this study was to investigate the
      relationship between single nucleotide polymorphisms (SNPs) in TGF-beta1 and
      chronic HCV infection among patients referred to the Taleghani Hospital, Tehran,
      Iran between 2008 and 2010. PATIENTS AND METHODS: In this case-control study,
      samples were collected using a convenience sampling method. We genotyped 164 HCV
      patients and 169 healthy controls for 3 SNPs in the TGF-beta1 gene (-509
      promoter, codon 10, and codon 25). We determined the SNP genotypes by using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re
      genotyped using a direct sequencing method. RESULTS: There were no significant
      differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T,
      or +915 G/C between HCV patients and the healthy controls. Genotyping results for
      all three polymorphic sites were similar with no statistically significant
      differences between the groups. CONCLUSIONS: Most of the Iranian patients (over
      85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C
      position, resulting in a high level of TGF-beta1 production. Therefore, we
      concluded that the SNPs investigated by us cannot be considered as prognostic
      factors for HCV infection in our population, despite being reported as prognostic
      markers in other populations. Moreover, there is a possibility that most of the
      population is susceptible to HCV infection.

PMID- 22363354
TI  - A glance to 2011.

PMID- 22363355
TI  - Occupational hazards to dental staff.
AB  - Dental professionals are predisposed to a number of occupational hazards. These
      include exposure to infections (including Human Immunodeficiency Virus and viral
      hepatitis); percutaneous exposure incidents, dental materials, radiation, and
      noise; musculoskeletal disorders; psychological problems and dermatitis;
      respiratory disorders; and eye insults. Percutaneous exposure incidents remain a
      main concern, as exposure to serious infectious agents is a virtual risk.
      Minimizing percutaneous exposure incidents and their consequences should continue
      to be considered, including sound infection control practices, continuing
      education, and hepatitis B vaccination. Basically, for any infection control
      strategies, dentists should be aware of individual protective measures and
      appropriate sterilization or other high-level disinfection utilities. Strained
      posture at work disturbs the musculoskeletal alignment and leads to stooped
      spine. The stooped posture also involved certain groups of muscles and joints.
      This may lead to diseases of the musculoskeletal system. Continuous educating and
      appropriate intervention studies are needed to reduce the complication of these
      hazards. So, it is important for dentists to remain constantly up-to-date about
      measures on how to deal with newer strategies and dental materials, and
      implicates the need for special medical care for this professional group.

PMID- 22363356
TI  - Comparative immunohistochemical analysis of angiogenesis and mast cell density in
      oral normal mucosa and squamous cell carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignancy in oral
      cavity. Angiogenesis is essential for the development and progression of SCC.
      Recently, some studies have reported that mast cells may play a role in tumor
      progression via promoting angiognesis. Since the results of various studies on
      the role of mast cells in tumor progression is not uniform, the aim of this study
      was to define the possible role of mast cells in the process of angiogenesis by
      determining the microvessel density (MVD) and mast cell density (MCD) and the
      association between them in oral normal mucsoa and oral SCC. MATERIALS AND
      METHODS: In this retrospective analytical study, paraffinized specimens from 22
      cases of normal mucosa and 20 cases of well-differentiated oral SCC were
      selected. Microvessels were stained by using immunohistochemical technique with
      anti-CD34 antibody and mast cells with toluidine blue and then were counted at
      400* magnification in hot-spot areas under a light microscope. The results were
      analyzed by using t- test and Pearson's exams. P values less than 0.05 was
      considered to be significant. RESULTS: A significant correlation was noted
      between MVD and MCD in normal oral mucosa (P<0.001), but in spite of a higher
      density of mast cells and microvessels observed in oral SCC compared to normal
      mucosa, there was no significant correlation between them (P=0.731). CONCLUSION:
      These findings showed that factors other than mast cells may play a role in the
      upregulation of tumor angiogenesis in oral SCC.

PMID- 22363357
TI  - Retentiveness of implant-supported metal copings using different luting agents.
AB  - BACKGROUND: With regard to potential retrievability of cement-retained implant
      restorations, the retentive strength of the luting agents is critical. The aim of
      this study was to evaluate the retention values of implant-supported metal
      copings using different luting agents. MATERIALS AND METHODS: Twenty ITI implant
      analogs and solid abutments of 5.5-mm height were embedded vertically in
      autopolymerizing acrylic resin blocks. Metal copings with a loop on the occlusal
      surface were fabricated using base metal alloy (Rexillium III). The copings were
      luted using eight cements with different retention mechanisms (Panavia F2.0, Fuji
      Plus, Fleck's, Poly F, Fuji I, Temp Bond, GC-free eugenol, and TempSpan) under
      static load of 5 kg (n=10). All specimens were incubated at 37 degrees C for 24
      hours, conditioned in artificial saliva for 7 days and thermocycled for 5000
      cycles (5-55 degrees C). The dislodging force was measured using a universal
      testing machine at a crosshead speed of 5 mm/min. Statistical analyses were
      performed using Kruskal-Wallis (alpha=0.05) and Mann-Whitney tests with
      Bonferroni correction (alpha=0.001). RESULTS: Fuji Plus and TempSpan had the
      highest and the least mean retentive strength, respectively (320.97+/-161.47,
      3.39+/-2.33). There was no significant difference between Fuji Plus, Fleck's,
      Ploy F, and Panavia F2.0. These cements were superior to provisional cements and
      Fuji I (P<0.001) which showed statistically same retentive strength. CONCLUSION:
      Within the conditions of this study, the resin modified glass ionomer, zinc
      phosphate, zinc polycarboxylate, and Panavia F2.0 had statistically the same
      retentive quality and are recommended for definitive cementation of single
      implant-supported restorations. The provisional cements and glass ionomer may
      allow retrievability of these restorations.

PMID- 22363358
TI  - Comparative analysis of salivary zinc level in recurrent herpes labialis.
AB  - BACKGROUND: Recurrent Herpes Labialis (RHL) is one of most common infective
      vesiculoulcerative lesions. According to some studies administration of topical
      and/or systemic zinc compositions has been effective in treatment and prevention.
      This article aims to comparison of zinc level in healthy subjects and RHL
      patients in acute and convalescent phases. MATERIALS AND METHODS: This was a
      retrospective case - control study, carried on 80 individuals (40 normal and 40
      RHL patients) mean age=34.5 and 34.4, respectively. Saliva samples were taken in
      patients in acute phase once and after healing of lesions in convalescent phase
      (averagely 21 days later) and in normal individuals. Salivary zinc level
      concentration was measured by flame atomic absorption spectrophotometer by dry
      digestion method. The results were statistically analyzed with SPSS software by t
      test (alpha=0.05). RESULTS: Results showed that salivary zinc level in case group
      in acute and convalescent phases were 160.8 (ngr)/(ml)and 205.7 (ngr)/(ml)
      respectivly and significant differences between them were existed (P <0.05). Also
      significant differences were existed between zinc concentration in healthy
      subjects and patient groups (in both phases) (P=.001 and .002 for acute and
      convalescent phases respectively). CONCLUSION: According to the results, zinc
      level is significantly lower in acute phase than in convalescent phase and
      significantly lower in both phases compared to healthy individuals,so
      determination of serum zinc level and prescribing zinc complement in low serum
      status has both treatmental and preventive effects in RHL patients.

PMID- 22363359
TI  - Effect of MTAD on the shear bond strength of self-etch adhesives to dentin.
AB  - BACKGROUND: As the use of different irrigants to eliminate residual debris and
      smear layer in the field of endodontic is unavoidable, by considering the effect
      of irrigants on the bond strength of resin composite restorations, this study was
      designed to evaluate the effect of a mixture of a tetracycline isomer, an acid,
      and a detergent (MTAD) on the shear bond strength of two self-etch adhesives,
      Clearfil SE Bond and Adper Prompt L- Pop to dentin. MATERIALS AND METHODS: The
      crowns of 80 extracted premolars were transversally sectioned to expose dentin.
      Flat dentin surfaces were wet abraded with 320-grit abrasive paper and randomly
      assigned to eight groups according to two self-etch adhesive and four dentin
      surface treatments: direct application over smear layer (no treatment), etching
      with 35% phosphoric acid for 15s, 1 min 5.25% NaOCl/1 min MTAD and 20min 1.3%
      NaOCl/5min MTAD. Shear bond strength was tested 24 h after storage in distilled
      water at 37 degrees C in incubator. Data were analyzed using one-way ANOVA
      followed by duncan post-hoc (alpha=0.05). RESULTS: Phosphoric acid etching prior
      to SE Bond application significantly decreased the shear bond strength to dentin
      (P<0.05). Application of MTAD clinical protocol (20min 1.3% NaOCl/5min MTAD) did
      not significantly decrease the shear bond strength of self-etch adhesives to
      dentin (P=0.745) CONCLUSIONS: Based on the results of present investigation, it
      seems that the use of clinical protocol of 1.3% NaOCl as a root canal irrigant
      and a 5-min application of MTAD as a final rinse to remove the smear layer has no
      adverse effect on the shear bond strength of self-etch adhesives to dentin.

PMID- 22363360
TI  - A four-week solubility assessment of AH-26 and four new root canal sealers.
AB  - BACKGROUND: The strong link between sealer solubility and periapical reinfection
      indicates that water solubility of new sealers should be studied. This study
      aimed to assess the water solubility of five root canal sealers (AH-26, Topseal,
      2-Seal, Acroseal, and Roeko Seal Automix [RSA]). MATERIALS AND METHODS: In this
      in vitro experimental study, 30 specimens were fabricated from each of the
      abovementioned sealants. Then they were weighed and randomly divided into three
      subgroups of 10 each (A, B, and C). They were set at 37 degrees C and 100% RH, in
      accordance with ANSI/ADA 57 and ISO 6876-2001 requirements. Afterward, the
      specimens in subgroups A were incubated at 37 degrees C and 100% RH for 24 hours,
      while the specimens in the subgroups B and C were incubated in the same
      conditions for 7 days and 28 days, respectively. After incubation, the specimens
      were dried with blotting paper and were incubated for 24 hours at 37 degrees C
      and 0% RH. Then they were weighed. The percentage of weight loss was regarded as
      water solubility. RESULTS: The mean solubility of the sealers AH-26, Acroseal,
      Topseal, 2-Seal, and RSA were 0.28%, 0.36%, 0.07%, 0.037%, and 0.141% after 24
      hours, respectively. After 28 days, their solubility were 1.75%, 0.746%, 0.082%,
      0.04%, and 0.517%, respectively. Only the solubility of the sealers 2-Seal and
      Topseal were not statistically different (P>0.3 [Tukey's]). Again only the
      solubility of 2-Seal and Topseal did not significantly increase between the 7(th)
      day and the 28(th) day of incubation (P>0.6 [paired-samples t]). CONCLUSION: All
      tested materials met the standards (maximum weight loss of 3% within 24 hours).
      However, the results of 2-Seal followed by Topseal were the most favorable ones.

PMID- 22363361
TI  - Comparison of oral Midazolam-Ketamine and Midazolam-Promethazine as sedative
      agents in pediatric dentistry.
AB  - BACKGROUND: Investigation was designed to evaluate the behavioral changes in
      children receiving dental treatment while they have been administered combination
      of Midazolam/Ketamine or Midazolam/Promethazine. MATERIALS AND METHODS: This was
      a randomized double blind clinical trial with cases being selected from those
      uncooperative children aged 2 to 6 years from those referred for treatment under
      general anesthesia. Anxiety score of all cases were recorded before any attempt
      using Frankel's anxiety scoring system with those in negative category being
      included. Cases with at least a pair of similar size cavities on similar teeth
      were selected with each tooth being randomly allocated for one sedative regimen
      group. To avoid sequence effect, half of the patients received one regimen at the
      first visit while the other half received the other regimen as the first. Each
      case served as control for him or herself to reduce influencing factors. Child's
      reaction was recorded before, during, and at the end of dental procedure. SO2 as
      well as Pulse rate were recorded as the most critical vital signs. Collected data
      were then analyzed using analysis of variance (ANOVA) and paired t-test. RESULTS:
      Patients' mean age was 3.5 years with 43% being male. Only 10% of the
      Ketamine/Midazolam group showed considerable amount of change in their behavior
      with a statistical significant difference being presented (P=0.029). CONCLUSION:
      Under the current circumstances, Ketamine/Midazolam combination provided
      sufficient sedative effect in lower doses. However, Midazolam/Promethazine
      combination did not produce similar results.

PMID- 22363362
TI  - Evaluating the levels of salivary alkaline and acid phosphatase activities as
      biochemical markers for periodontal disease: A case series.
AB  - BACKGROUND: The purpose of this study was to determine the salivary levels of
      alkaline phosphatase (ALP) and acid phosphatase (ACP) activities in patients with
      periodontal disease and to evaluate the use of these enzymes as biochemical
      markers for periodontal tissue damage. MATERIALS AND METHODS: In this prospective
      analytical study, we examined the activities of salivary ALP and ACP in patients
      with periodontal disease, before and after periodontal treatment. The
      experimental groups consisted of 20 gingivitis patients and 20 periodontitis
      patients and the control group had healthy subjects (20 samples). The stimulated
      saliva of the patient was collected in a sterile test tube and analyzed using
      Hitachi's Diagnostic Automatic Analyser. Periodontal disease was determined based
      on clinical parameters such as gingival index, probing depth and clinical
      attachment loss. Patients with periodontal disease were under conventional
      periodontal treatment. The statistical analysis applied was Student's t-test.
      Probabilities less than 0.05 (P < 0.05) were considered significant. RESULTS: The
      obtained results showed statistically significant increased activities of ALP and
      ACP in saliva from patients with periodontal disease in relation to control
      group. A significant reduction in the enzyme levels was seen after conventional
      periodontal therapy. CONCLUSIONS: Based on these results, salivary ALP and ACP
      can be considered to be the biomarkers for evaluating periodontal tissue damage.

PMID- 22363363
TI  - Post-bleaching application of an antioxidant on dentin bond strength of three
      dental adhesives.
AB  - BACKGROUND: Antioxidizing agents have recently been suggested to compensate
      decreased bond strength of resin materials to bleached tooth tissues. This study
      compared the shear bond strength (SBS) of three different adhesives on bleached
      dentin immediately after bleaching, bleached/delayed for 1 week, and
      bleached/applied antioxidizing agent. MATERIALS AND METHODS: The dentinal
      surfaces of 132 intact extracted molars were prepared and divided into 12 groups.
      The following adhesives were investigated: Optibond FL (OFL) (three-step etch-and
      rinse), Optibond Solo Plus (two-step etch-and-rinse), and Optibond all-in-one
      (OA) (one-step self-etch) (Kerr, Orange, USA). Unbleached dentin groups (groups 1
      3) were prepared as negative controls (NC). The remainder surfaces (groups 4-12)
      were bleached with 20% Opalescent PF (Ultradent, USA). Specimens were bonded
      immediately after bleaching (groups 4-6), after 1 week (groups 7-9), or after
      using 10% sodium ascorbate (SA) gel (groups 10-12). Subsequent to bonding of
      composite resin, the samples were tested for SBS and analyzed using Kruskal
      Wallis and Mann-Whitney tests (alpha=0.05). RESULTS: Regarding control groups, OA
      showed the highest SBS among the studied adhesives (P<0.05). The SBS decreased
      for the adhesives after bleaching except for OFL. No statistically significant
      difference in SBS were noted when the SA and delayed bonding groups were compared
      with their similar NC groups (P>0.05) except the of delay bonding with OA.
      CONCLUSIONS: The findings suggest that bond strength of resin to bleached dentin
      may be affected with the adhesive system. Reduced SBS to bleached dentin can be
      amended by the use of SA as an antioxidizing agent. However, the amount of
      reversed bond strength subsequent to applying antioxidant might be related to the
      kind of dental adhesive.

PMID- 22363364
TI  - Biocompatibility of mineral trioxide aggregate and three new endodontic cements:
      An animal study.
AB  - BACKGROUND: Introducing new endodontic cements should await comprehensive
      investigations and new formulations have to be tested in vivo before applying in
      human beings. So, the purpose of this study was to compare the biocompatibility
      of new endodontic cements, calcium aluminate alpha-aluminate cement (CAAC),
      calcium aluminate alpha-aluminate plus cement (CAAC plus), and a mixture of
      wollastonite and CAAC cement (WOLCA) and mineral trioxide aggregate (MTA), in
      subcutaneous connective tissue of rats. MATERIALS AND METHODS: Twenty-seven
      Wistar rats were divided into three groups of 7, 14, and 30 experimental days.
      Sterile polyethylene tubes were filled with MTA, CAAC, CAAC Plus, and WOLCA
      cement and implanted subcutaneously. Empty tubes were implanted as negative
      control. After the experimental periods, animals were sacrificed by anesthetic
      overdosing. The occurrence of inflammatory responses was scored according to the
      previously established scores. Data were statistically analyzed using Friedman,
      Wilcoxon, Kruskal-Wallis, and Mann-Whitney tests. The level of significance was
      5% (P<0.05). RESULTS: There was a statistically significant difference between
      experimental and negative control sites in each group (P<0.05). CAAC Plus showed
      the highest mean scores of inflammation, compared with MTA, CAAC, and WOLCA
      cement sits at the end of all periods (P<0.05). There were no statistically
      significant differences between inflammatory scores of each site in different
      experimental groups, except CAAC plus sites, in which inflammation increased
      significantly with time (P<0.05). CONCLUSION: According to the results of the
      current study, biocompatibility of CAAC and WOLCA cement were comparable with
      that of MTA, but CAAC Plus induced an inflammatory response higher than MTA,
      therefore is not biocompatible.

PMID- 22363365
TI  - Clinical and radiographic evaluation of Nano-crystalline hydroxyapatite bone
      graft (Sybograf) in combination with bioresorbable collagen membrane (Periocol)
      in periodontal intrabony defects.
AB  - BACKGROUND: Nanosized ceramics may represent a promising class of bone graft
      substitutes due to their improved osseointegrative properties. Nanocrystalline
      Hydroxyapatite (NcHA) bind to bone and stimulate bone healing by stimulation of
      osteoblast activity. The present study aims to explore the clinical and
      radiographical outcome of NcHA bonegraft (Sybograf((r))) with collagen membrane
      (Periocol((r))), in comparison with open flap debridement (OFD), in the treatment
      of intrabony periodontal defects. MATERIALS AND METHODS: A parallel-group,
      randomized, controlled clinical trial was designed to conduct the study. Eighteen
      intrabony defects in 14 systemically healthy patients aged between 25 to 65 years
      were randomly assigned to test and control group. The plaque index, gingival
      index, probing pocket depth (PPD), clinical attachment level (CAL), and gingival
      recession (REC) were recorded at baseline, and were reevaluated at 6 months. In
      addition to this, radiographic bone fill was assessed using digital software. At
      the test site, NcHA bone graft and collagen membrane was placed, whereas at the
      control site, only OFD was done. Recall appointments were made at 7 days, 30
      days, and then at 3 months and 6 months. RESULTS: The data were subjected to
      statistical analysis using the Mann-Whitney 'U' Test and Wilcoxon signed rank sum
      test. In the control group, the mean reduction of PPD was 3.22+/-1.09 mm
      (P=0.007) and CAL gain was 2.77+/-1.09 mm (P=0.007). In the test group, the mean
      PPD reduction of 4.33+/-0.5 mm (P=0.006) and mean gain in CAL was 3.77+/-0.66 mm
      (P=0.006) at 6 months. The mean increase in REC was 0.55+/-0.72 mm (P=0.025) in
      test, and 0.44+/-0.52 mm (P=0.046) in control group. The mean gain in
      radiographic defect fill was 2.07+/-0.67 mm (P=0.008) in test and 0.91+/-0.21 mm
      (P=0.007) in control group. CONCLUSION: The nanocrystalline hydroxyapatite bone
      graft in combination with collagen membrane demonstrated clinical advantages
      beyond that achieved by OFD alone.

PMID- 22363366
TI  - Comparative efficacy of dentifrice containing sodium monofluorophosphate +
      calcium glycerophosphate and non-fluoridated dentifrice: A randomized, double
      blind, prospective study.
AB  - BACKGROUND: The efficacy of fluoridated dentifrices in caries prevention has been
      well documented and research into various formulations continues for a more
      effective dentifrice. This study evaluated the anti-caries and anti-plaque
      efficacy of a dentifrice containing sodium monofluorophosphate (1000 ppm) and
      calcium glycerophosphate, and compared it with a non-fluoridated dentifrice.
      MATERIALS AND METHODS: A total of 595 school children (12-15 years) were divided
      into test (302 children) and control (293 children) groups. The test group used
      the dentifrice containing sodium monofluorophosphate (1000 ppm) and calcium
      glycerophosphate, whereas the control group was given a placebo dentifrice. Oral
      examination for dental caries and plaque assessment was carried out at the start
      of the study and the children were followed up semiannually up to 18 months. Data
      were analyzed using repeated-measure analysis of variance (ANOVA) followed by one
      way ANOVA. RESULTS: The values for decayed missing filled teeth (DMFT) increased
      from baseline to 18 month examination from 4.43+/-2.03 and 4.67+/-2.25 (P=0.175)
      to 5.84+/-2.29 and 5.13+/-2.30 (P=0.001) for control and test groups,
      respectively. Similarly, the increase in decayed missing filled surface (DMFS)
      values were from 6.42+/-4.10 and 7.06+/-4.77 (P=0.082) to 8.64+/-4.51 and 7.92+/
      5.07 (P=0.095) for test and control groups, respectively. The mean DMFT and DMFS
      values increased for both the groups; however, the increase was less in test
      group as compared to control group. The baseline plaque score reduced from 2.94+/
      0.72 and 2.91+/-0.72 (P=0.679), respectively, for control and test groups to
      1.33+/-0.46 and 0.91+/-0.38 (P<0.001), respectively, at 18 month examination.
      CONCLUSION: Results revealed that the test dentifrice was effective in inhibiting
      the progression of plaque and control of dental caries as compared to the placebo
      dentifrice.

PMID- 22363367
TI  - Comparison of cardiovascular disease risk in two main forms of periodontitis.
AB  - BACKGROUND: C-reactive protein (CRP) is an acute phase reactant and has been
      proved to be a significant predictor of future cardiovascular events. Recent
      studies have demonstrated a correlation between periodontitis and elevated CRP
      levels. However, comparison between the levels of CRP in two main forms of
      periodontitis is ambiguous. This study aims at determining and comparing the
      relative levels of serum CRP in aggressive and chronic periodontitis patients.
      MATERIALS AND METHODS: A total of 240 systemically healthy subjects were divided
      into three groups of 80 based on having generalized aggressive periodontitis,
      chronic generalized periodontitis and non-periodontitis (NP; controls). Venous
      blood samples were collected for quantitative CRP analysis using turbidimetric
      immunoassay. RESULTS: Mean CRP levels were significantly greater in both
      generalized aggressive periodontitis (7.49+/-2.31 mg/l) and chronic generalized
      periodontitis (4.88+/-1.80 mg/l) groups as compared to NP (0.68+/-0.23 mg/l)
      controls. Moreover, CRP levels were significantly higher in aggressive
      periodontitis as compared to chronic periodontitis patients. Also, CRP levels
      positively correlated with the amount of periodontal destruction as measured by
      probing depth and clinical attachment loss for both chronic generalized
      periodontitis and generalized aggressive periodontitis. CONCLUSION: Findings of
      the present study indicated that periodontitis should be of particular concern in
      younger individuals, where elevated levels of CRP may contribute to early or more
      rapid cardiovascular disease in susceptible patients. Thus, further research
      should be carried out at a community level to ascertain these findings.

PMID- 22363368
TI  - A clinical and fine needle aspiration cytology study of gingiva in acute
      leukemia.
AB  - BACKGROUND: Oral manifestations are frequently the initial signs of acute
      leukemia, prompting the patient to consult the dentist first. The gingival tissue
      is one site commonly involved either by leukemic infiltration or by inflammatory
      reactive hyperplasia, causing gingival enlargement. The gingival infiltration may
      also be present without gingival enlargement. Early recognition of clinical
      findings in the oral cavity leads to its timely diagnosis and management. Since
      biopsy is highly contraindicated, gingival fine needle aspiration cytology was
      performed to assess its diagnostic value in detecting gingival infiltration in
      acute leukemia patients. MATERIALS AND METHODS: Fifty patients of acute leukemia
      received clinical and gingival cytological examination. The cases were diagnosed
      based on bone marrow aspiration findings and classified according to the French
      American-British criteria. The absence or presence of intraoral findings was
      recorded. Site for gingival fine needle aspiration cytology was selected.
      RESULTS: Leukemic gingival infiltration was found to be more common in acute
      lymphoblastic leukemia, while the characteristic oral findings were seen more
      commonly in acute myeloblastic leukemia. All the eight cases of acute
      lymphoblastic leukemia that were positive for leukemic gingival infiltration
      showed no clinical evidence of gingival enlargement. In terms of leukemic
      gingival infiltration, L2 subtype was the only subtype involved, while M5 was
      more commonly involved than M4 subtype. Two cases of L2 subtype showed gingival
      enlargement due to local factors like plaque/calculus rather than due to leukemic
      infiltration. CONCLUSION: The technique was found to be safe and of definitive
      diagnostic value in detecting gingival infiltration in acute leukemia patients.

PMID- 22363369
TI  - Comparison of cell viability and morphology of a human osteoblast-like cell line
      (SaOS-2) seeded on various bone substitute materials: An in vitro study.
AB  - BACKGROUND: Many studies have shown favorable results following the use of
      different bone graft materials. The aim of the present study was to evaluate the
      biocompatibility of four different bone graft materials regarding cell viability
      and morphology of Human osteoblast-like cells (SaOS-2) in vitro. MATERIALS AND
      METHODS: The effects of Bio-Oss((r)), Tutodent((r)), Osteon((r)), and
      Cerasorb((r)) were studied on the human osteoblast-like cell line to evaluate
      various parameters. Human osteoblast-like cells were seeded onto the mentioned
      bone substitute materials (BSMs). Cell differentiation; cell viability and
      alkaline phosphatase (ALP) activity of the seeded cells were evaluated by means
      of scanning electron microscopy, cell viability test and phase contrast
      microscopy Analysis of variance (ANOVA). Tamhane's post-hoc, Kruskal-Wallis Test,
      and Dunn's Test were used. The results were considered to be statistically
      significant at P<0.05. RESULTS: The control group (SaOS-2 cells which were
      incubated in Dulbecco Modified Eagle Medium without any kind of bone graft
      materials) had the highest level of cell viability (P<0.001), followed by
      Tutodent((r)), Osteon((r)), Cerasorb((r)), and Bio-Oss((r)). There was no
      significant difference in MTT assay results between Tutodent((r)) and the control
      group (P=0.032). All tested bone graft materials showed significantly higher ALP
      activity than the control (P<0.001). The Tutodent((r)) group showed the best cell
      growth among all experimental groups, followed by the Osteon((r)) group. The
      former had a higher spindle-like morphology with good attachment to the surface.
      Cells cultivated on the surfaces of the Cerasorb((r)) and Bio-Oss((r)) granules
      had more round morphologies. CONCLUSION: This in vitro study demonstrated that
      all tested BSMs can provide good cell differentiation but a lower rate of
      proliferation.

PMID- 22363370
TI  - Effect of plasma-rich in platelet-derived growth factors on peri-implant bone
      healing: An experimental study in canines.
AB  - BACKGROUND: Tissue engineering principles can be exploited to enhance alveolar
      and peri-implant bone reconstruction by applying such biological factors as
      platelet-derived growth factors. The objective of the present study is to
      investigate the effect of autologous plasma-rich in growth factors (on the
      healing of peri-implant bone in canine mandible). MATERIALS AND METHODS: In this
      prospective experimental animal study, two healthy canines of the Iranian mix
      breed were selected. Three months after removing their premolar teeth on both
      sides of the mandible, 12 implants of the Osteo Implant Corporationsystem, 5 mm
      in diameter and 10 mm in length, were selected to be implanted. Plasma rich in
      growth factors (PRGF) were applied on six implants while the other six were used
      as plain implants without the plasma. The implants were installed in osteotomy
      sites on both sides of the mandible to be removed after 4 weeks with the
      surrounding bones using a trephine bur. Mesio-distal sections and implant blocks,
      50 MU in diameter containing the peri-implant bone, were prepared By basic fuchin
      toluidine-bluefor histological and histomorphometric evaluation by optical
      microscope. The data were analyzed using Mann-Whitney Test (P<0.05). RESULTS: The
      bone trabeculae and the type of bone generation in PRGF and control groups had no
      statistically significant differences (P=0.261, P=0.2) although the parameters
      showed higher measured values in the PRGF group. However, compared to the
      control, application of PRGF had significantly increased bone-to-implant contact
      (P=0.028) CONCLUSION: Based on the results, it may be concluded that application
      of PRGF on the surface of implant may enhance bone-to-implant contact.

PMID- 22363371
TI  - Gorlin-Goltz syndrome.
AB  - Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which
      is characterized by multiple odontogenic Keratocysts and basal cell carcinomas,
      skeletal, dental, ophthalmic, and neurological abnormalities, intracranial
      ectopic calcifications of the falx cerebri, and facial dysmorphism. Pathogenesis
      of the syndrome is attributed to abnormalities in the long arm of chromosome 9
      (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Diagnosis
      is based upon established major and minor clinical and radiological criteria and
      ideally confirmed by deoxyribo nucleic acid analysis. We report a case of a 9
      year-old girl presenting with three major and one minor feature of Gorlin-Goltz
      syndrome. Radiologic findings of the syndrome are easily identifiable on
      Orthopantomogram, chest X-ray, and Computed tomography scans. These
      investigations prompt an early verification of the disease, which is very
      important to prevent recurrence and better survival rates from the coexistent
      diseases.

PMID- 22363372
TI  - Non-invasive management of fused upper incisors.
AB  - The union of two different dental sprouts which can happen in any phase of dental
      development is commonly called fusion. This developmental anomaly may cause
      clinical problems including esthetic impairment, which are mainly treated by
      endodontic and surgical treatments. There are a few reports of conservative not
      invasive treatment of fused incisors teeth through restorative or prosthetic
      techniques. They are rarely reported in mandibular posterior teeth. This paper
      presents an unusual case of fusion of 7 and 8, and also 9 and 10 teeth which was
      treated with a nonendodontic and nonsurgical conservative approach. Patient was a
      healthy18-year-old female with chief complaint of bad-looking teeth that in
      intraoral examination revealed the fusion of 7 and 8, and also 9 and 10 teeth.
      The space between the mesial of the 6 and 11 teeth was reconstructed. Diastema
      between the fused teeth was closed. A new lateral tooth was replaced between the
      fused teeth (7 and 8) and 6 tooth with direct fiber-reinforced composite. The
      space between the fused teeth (9 and 10) and also tooth 11 was partially closed.
      Gingival papillas were reconstructed using pink composite. The mandibular
      anterior missing teeth were replaced with rochett bridge. At the end of treatment
      the esthetic of the patient was improved. As the treatment was not invasive,
      major complications are not expected; however, there is potential for eventual
      long-term periodontal problems due to poor oral hygiene. Debonding of the rochett
      bridge may happen as well.

PMID- 22363373
TI  - Rabbit as an animal model for experimental research.
AB  - Animal experimentation is carried out in consultation with the veterinary wing
      but it is essential that be familiar with experimental protocols of animal model
      to be able to design an approriate study. This is more so in place where the
      veterinary facilities are not easily available.Span Rabbits are commonly used as
      subjects for screening implant material. They have gained favour for their
      numerous advantages even though they should be ideally used prior to testing in a
      larger animal model. Though experimentation on rabbits seems to be easy there are
      many pitfalls. Our endeavor in this article is to integrate all the data about
      maintaining rabbits as a model and to critically analyze it on the basis of our
      experimentation.

PMID- 22363374
TI  - Is flavor component in dental product therapeutic?

PMID- 22363375
TI  - Forensic odontology as an aid for victim identification in mass disasters.

PMID- 22363376
TI  - Surgical management of chronic pulmonary regurgitation after relief of right
      ventricular outflow tract obstruction.
AB  - Relief of right ventricular (RV) outflow tract obstruction in tetralogy of Fallot
      or similar physiology often results in pulmonary regurgitation (PR). The
      resultant chronic volume overload can lead to RV dilatation, biventricular
      dysfunction, heart failure symptoms, arrhythmias and sudden death. Although
      pulmonary valve replacement (PVR) can lead to improvement in the functional class
      and a substantial decrease or normalization of RV volumes, the optimal timing of
      PVR is not well defined. Benefits of PVR have to be weighed against the risks of
      this procedure including subsequent reoperation. This article reviews the
      pathophysiology of chronic PR, evidence-based benefits and risks of PVR, options
      for valve substitute, and optimal timing of PVR in patients with chronic PR after
      relief of RV outflow tract obstruction.

PMID- 22363377
TI  - Pulmonary artery stents-still "off label".

PMID- 22363378
TI  - Validity of the diagnosis of acute myocardial infarction in korean national
      medical health insurance claims data: the korean heart study (1).
AB  - BACKGROUND AND OBJECTIVES: Medical insurance claims (MIC) data are one of the
      largest sources of outcome data in the form of International Classification of
      Diseases (ICD) codes. We evaluated the validity of the ICD codes from the Korean
      National MIC data with respect to the outcomes from acute myocardial infarction
      (AMI) in the Korean Heart Study. SUBJECTS AND METHODS: Baseline information was
      obtained from health examinations conducted from 1994 to 2001. Outcome
      information regarding the incidence of AMI came from hospital admission discharge
      records from 1994 to 2007. Structured questionnaires were sent to 98 hospitals.
      In total, 107 cases of AMI with ICD codes of I21- (93 men, 26-73 years of age)
      were included in the final analyses. ICD code accuracy and reliability (kappa)
      for AMI were calculated. RESULTS: A large number of AMI cases were from hospitals
      located in the Seoul area (75.9%). The accuracy of AMI was 71.4%, according to
      World Health Organization criteria (1997-2000, n=24, kappa=0.46) and 73.1%
      according to the European Society of Cardiology/American College of Cardiology
      (ESC/ACC) criteria (2001-2007, n=83, kappa=0.74). An age of 50 years or older was
      the only factor related to inaccuracy of codes for AMI (odds ratio, 4.6; 95%
      confidence interval, 1.2-17.7) in patients diagnosed since January 2001 using
      ESC/ACC criteria (n=83). CONCLUSION: The accuracy for diagnosing AMI using the
      ICD-10 codes in Korean MIC data was >70%, and reliability was fair to good;
      however, more attention is required for recoding ICD codes in older patients.

PMID- 22363379
TI  - Atypical symptom cluster predicts a higher mortality in patients with first-time
      acute myocardial infarction.
AB  - BACKGROUND AND OBJECTIVES: Identifying symptom clusters of acute myocardial
      infarction (AMI) and their clinical significance may be useful in guiding
      treatment seeking behaviors and in planning treatment strategy. The aim of this
      study was to identify clusters of acute symptoms and their associated factors
      that manifested in patients with first-time AMI, and to compare clinical outcomes
      among cluster groups within 1-year of follow-up. SUBJECTS AND METHODS: A total of
      391 AMI patients were interviewed individually using a structured questionnaire
      for acute and associated symptoms between March 2008 and June 2009 in Korea.
      RESULTS: Among 14 acute symptoms, three distinct clusters were identified by
      Latent Class Cluster Analysis: typical chest symptom (57.0%), multiple symptom
      (27.9%), and atypical symptom (15.1%) clusters. The cluster with atypical
      symptoms was characterized by the least chest pain (3.4%) and moderate
      frequencies (31-61%) of gastrointestinal symptoms, weakness or fatigue, and
      shortness of breath; they were more likely to be older, diabetic and to have
      worse clinical markers at hospital presentation compared with those with other
      clusters. Cox proportional hazards regression analysis showed that, when age and
      gender were adjusted for, the atypical symptom cluster significantly predicted a
      higher risk of 1-year mortality compared to the typical chest pain cluster
      (hazard ratio 3.288, 95% confidence interval 1.087-9.943, p=0.035). CONCLUSION:
      Clusters of symptoms can be utilized in guiding a rapid identification of symptom
      patterns and in detecting higher risk patients. Intensive treatment should be
      considered for older and diabetic patients with atypical presentation.

PMID- 22363380
TI  - Protective effects of peroxiredoxin on hydrogen peroxide induced oxidative stress
      and apoptosis in cardiomyocytes.
AB  - BACKGROUND AND OBJECTIVES: The redox system is an important anti-oxidative system
      composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine
      details of PRx expression and its protective effects in various cells in
      cardiovascular tissue under oxidative stress created by hydrogen peroxide have
      not been fully elucidated. SUBJECTS AND METHODS: Oxidative stress was induced by
      adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes
      (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein
      endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the
      expression patterns of the six PRx isoforms were evaluated by western blotting in
      the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell
      survival signal pathway were evaluated by PRx1 gene delivery using lentiviral
      vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein
      gene delivery. RESULTS: Hydrogen peroxide induced 25% apoptosis in rCMCs.
      Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen
      peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to
      reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this
      effect was found to originate from cell survival pathway modification.
      CONCLUSION: Hydrogen peroxide induced significant oxidative stress in rCMCs,
      rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system
      significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation
      of cell survival signals and downregulation of apoptotic signals. These findings
      suggest that PRx1 could be used as a treatment strategy for myocardial salvage in
      conditions of oxidative stress.

PMID- 22363381
TI  - Fibro-Fatty Component is Important for the Long-Term Clinical Events in Patients
      Who Have Undergone Primary Percutaneous Coronary Intervention.
AB  - BACKGROUND AND OBJECTIVES: We evaluated which plaque components are associated
      with long-term clinical events in patients who underwent primary percutaneous
      coronary intervention (PCI). SUBJECTS AND METHODS: The study subjects consisted
      of 57 consecutive patients (mean age, 58.5+/-14.5 years; 45 males) who underwent
      primary PCI and a virtual histology-intravascular ultrasound examination. Major
      adverse cardiac events (MACEs) including death, acute myocardial infarction,
      stroke, and revascularization were evaluated during the mean 28 month follow-up
      period. RESULTS: Patients with high fibro-fatty volume (FFV >13.4 mm(3), n=29;
      mean age, 61.3 years) had a lower ejection fraction (52.7% vs. 59.4%, p=0.022), a
      higher incidence of multi-vessel disease (69.0% vs. 28.6%, p=0.002), larger
      plaque area (25.7 mm(2) vs. 15.9 mm(2), p<0.001), and larger plaque volume (315
      mm(3) vs. 142 mm(3), p<0.001) than those with a low FFV (<=13.4 mm(3), n=28; mean
      age, 55.6 years). Patients with high FFV had a significantly higher incidence
      (32.1% vs. 8.3%, p=0.036) of MACE than those with low FFV. When we divided the
      study population according to the necrotic core volume (NCV), fibrous volume, or
      dense calcified volume, no significant findings in terms of demographics and MACE
      rates were observed. A Cox regression analysis revealed that the independent
      factor for MACE was FFV (hazard ratio, 6.748; 95% confidence interval, 1.168
      38.971, p=0.033) in this study population. CONCLUSION: The coronary plaque
      component, particularly FFV, but not NCV, was important in long-term clinical
      outcomes in patients who underwent primary PCI.

PMID- 22363382
TI  - Effectiveness and safety of percutaneous transcatheter implantation of pulmonary
      arterial stent in congenital heart disease.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary arterial stenosis is a relatively common
      complication after corrective operation of congenital heart disease. Unilateral
      stenosis of pulmonary arteries could result in decrease perfusion of affected
      lung, pulmonary regurgitation, or elevation of right ventricular pressure.
      Eventually there are increasing risks of right ventricular failure, arrhythmia,
      or sudden death. However we have limited data of pulmonary arterial stent in
      paediatric population as the treatment of branch pulmonary stenosis. This study
      aimed at validating the effectiveness and investigating complications of
      pulmonary arterial stent implantation in a single institution during mid-term
      follow up period. SUBJECTS AND METHODS: A total of 42 patients (50 stents) were
      implanted for treating branch pulmonary arterial stenosis. We used cardiac
      catheterization for comparing diameter after stent implantation directly and lung
      perfusion scan indirectly. We also investigated any adverse effect relating the
      procedure. RESULTS: Percent stenosis of stenotic lesions were decreased from
      54.1+/-10.7% to 22.8+/-12.5% (p<0.001) and degree of decrement in affected lung
      perfusion was declined from 22.7+/-8.0% to 10.3+/-9.0% (p<0.001) immediately and
      lasts during mid-term follow up period. Complication rate relating the procedure
      was 12% (6 out of 12) and there was no mortality case. CONCLUSION: This series
      showed immediate and short term effectiveness of pulmonary arterial stent in
      congenital heart defects. We concluded that percutaneous transcatheter
      implantation of pulmonary arterial stent was safe and effective during short and
      mid-term follow up period.

PMID- 22363383
TI  - A butterfly-shaped primary cardiac lymphoma that showed bi-atrial involvement.
AB  - We described here a patient who presented with symptoms of heart failure who was
      found to have severe bilateral impairment of atrioventricular inflow. Primary
      cardiac lymphoma (PCL) with extensive involvement of the two atria, pericardium
      and myocardium is an extremely rare tumor in immunocompetent patients. We report
      here a case of PCL in an immunocompetent patient with involvement of both atria
      and the atrial septum. The tumor had a butterfly shape. We could not do surgical
      excision because of the massive pericardiac invasion. The diagnosis was B-cell
      lymphoma and this was confirmed by the pericardiac biopsy.

PMID- 22363384
TI  - A Case of Acute Myocardial Infarction With ST-Segment Elevation in a Lead
      Augmented Right Vector Caused by a Left Main Coronary Artery Vasospasm.
AB  - Diagnosing and selecting an appropriate treatment strategy for left main coronary
      artery (LMCA) obstruction is very important. Although this disease is not
      frequently encountered, it can cause severe hemodynamic deterioration resulting
      in a less favorable prognosis without a suitable management approach. Another
      aspect of LMCA that we must not overlook is coronary artery spasm, which can be
      an infrequent but important cause of acute coronary syndrome. Although it is
      rare, LMCA can cause critical complications. In this study, we report the case of
      a 35-year-old female who was admitted to the hospital with a diagnosis of acute
      myocardial infarction with ST-segment elevation in the aVR lead caused by a left
      main coronary spasm that was examined on intravascular ultrasound.

PMID- 22363385
TI  - A case of late stent thrombosis following platelet transfusion in a patient with
      aplastic anemia.
AB  - Aplastic anemia is a condition in which the bone marrow fails to produce adequate
      numbers of peripheral blood elements. The incidences of atherosclerosis and
      myocardial infarction in patients with congenital coagulation disorders and
      chronic thrombocytopenia are very low. In this paper, a case of late stent
      thrombosis within a drug-eluting stent occurring after platelet transfusion in a
      patient with aplastic anemia is presented. The authors' observations emphasize
      the risks of platelet transfusion and the authors' support withholding such a
      treatment unless vitally indicated, in patients with coronary artery stent
      implantation and even in those on dual antiplatelet therapy.

PMID- 22363386
TI  - Successful management of a rare case of stent fracture and subsequent migration
      of the fractured stent segment into the ascending aorta in in-stent restenotic
      lesions of a saphenous vein graft.
AB  - Stent fracture is a complication following implantation of drug eluting stents
      and is recognized as one of the risk factors for in-stent restenosis. We present
      the first case of successfully managing a stent fracture and subsequent migration
      of the fractured stent into the ascending aorta that occurred during repeat
      revascularization for in-stent restenosis of an ostium of saphenous vein graft
      after implantation of a zotarolimus-eluting stent. Although the fractured stent
      segment had migrated into the ascending aorta with a pulled balloon catheter, it
      was successfully repositioned in the saphenous vein graft using an inflated
      balloon catheter. Then, the fractured stent segment was successfully connected to
      the residual segment of the zotarolimus-eluting stent by covering it with an
      additional sirolimuseluting stent.

PMID- 22363387
TI  - Severe aortic coarctation in a 75-year-old woman: total simultaneous repair of
      aortic coarctation and severe aortic stenosis.
AB  - Aortic coarctation is usually diagnosed and repaired in childhood and early
      adulthood. Survival of a patient with an uncorrected coarctation to more than 70
      years of age is extremely unusual, and management strategies for these cases
      remain controversial. We present a case of a 75-year-old woman who was first
      diagnosed with aortic coarctation and severe aortic valve stenosis 5 years ago
      and who underwent a successful one-stage repair involving valve replacement and
      insertion of an extra-anatomical bypass graft from the ascending to the
      descending aorta.

PMID- 22363388
TI  - Spontaneous sinus conversion of permanent atrial fibrillation during treatment of
      hyperkalemia.
AB  - Hyperkalemia is a common adverse effect of treatment for heart failure and is
      associated with high mortality and morbidity. The cardiac manifestations of
      hyperkalemia include various electrocardiogram changes. We describe a case of a
      74-year-old woman with heart failure and permanent atrial fibrillation who
      reverted to normal sinus rhythm during recovery from hyperkalemia.

PMID- 22363389
TI  - Coronary artery fistula with a huge aneurysm formation presenting as heart
      failure.

PMID- 22363390
TI  - How to write an article: Preparing a publishable manuscript!
AB  - Most of the scientific work presented as abstracts (platforms and posters) at
      various conferences have the potential to be published as articles in peer
      reviewed journals. This DIY (Do It Yourself) article on how to achieve that goal
      is an extension of the symposium presented at the 36(th) European Congress of
      Cytology, Istanbul, Turkey (presentation available on net at
      http://alturl.com/q6bfp). The criteria for manuscript authorship should be based
      on the ICMJE (International Committee of Medical Journal Editors) Uniform
      Requirements for Manuscripts. The next step is to choose the appropriate journal
      to submit the manuscript and review the 'Instructions to the authors' for that
      journal. Although initially it may appear to be an insurmountable task, diligent
      organizational discipline with a little patience and perseverance with input from
      mentors should lead to the preparation of a nearly perfect publishable manuscript
      even by a novice. Ultimately, the published article is an excellent track record
      of academic productivity with contribution to the general public good by
      encouraging the exchange of experience and innovation. It is a highly rewarding
      conduit to the personal success and growth leading to the collective achievement
      of continued scientific progress. Recent emergences of journals and publishers
      offering the platform and opportunity to publish under an open access charter
      provides the opportunity for authors to protect their copyright from being lost
      to conventional publishers. Publishing your work on this open platform is the
      most rewarding mission and is the recommended option in the current modern
      era.[This open access article can be linked (copy-paste link from HTML version of
      this article) or reproduced FREELY if original reference details are prominently
      identifiable].

PMID- 22363391
TI  - Comparing endobronchial ultrasound-guided fine needle aspiration specimens with
      and without rapid on-site evaluation.

PMID- 22363392
TI  - Authors' reply.

PMID- 22363393
TI  - Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on
      breast carcinoma aspirates and histopathology.
AB  - BACKGROUND: Fine needle aspiration (FNA) is a quick, minimally invasive procedure
      for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR) grade on
      histological sections is a well-established tool to guide selection of adjuvant
      systemic therapy. Grade evaluation is possible on cytology smears to avoid and
      minimize the morbidity associated with overtreatment of lower grade tumors. AIM:
      The aim was to test the hypothesis whether breast FNA from the peripheral portion
      of the lesion is representative of Scarff-Bloom-Richardson grade on
      histopathology as compared to FNA from the central portion. MATERIALS AND
      METHODS: Fine-needle aspirates and subsequent tissue specimens from 45 women with
      ductal carcinoma (not otherwise specified) were studied. FNAs were performed
      under ultrasound guidance from the central as well as the peripheral third of the
      lesion for each case avoiding areas of necrosis/calcification. The SBR grading
      was compared on alcohol fixed aspirates and tissue sections for each case.
      RESULTS: Comparative analysis of SBR grade on aspirates from the peripheral
      portion and histopathology by the Pearson chi-square test (chi(2) =78.00) showed
      that it was statistically significant (P<0.001) with 93% concordance. Lower
      mitotic score on aspirates from the peripheral portion was observed in only 4 out
      of 45 (9%) cases. The results of the Pearson chi-square test (chi(2) = 75.824)
      with statistically significant (P=0.000). CONCLUSION: This prospective study
      shows that FNA smears from the peripheral portion of the lesion are
      representative of the grading performed on the corresponding histopathological
      sections. It is possible to score and grade by SBR system on FNA smears.

PMID- 22363395
TI  - A simple mathematical model based on the cancer stem cell hypothesis suggests
      kinetic commonalities in solid tumor growth.
AB  - BACKGROUND: The Cancer Stem Cell (CSC) hypothesis has gained credibility within
      the cancer research community. According to this hypothesis, a small
      subpopulation of cells within cancerous tissues exhibits stem-cell-like
      characteristics and is responsible for the maintenance and proliferation of
      cancer. METHODOLOGIES/PRINCIPAL FINDINGS: We present a simple compartmental
      pseudo-chemical mathematical model for tumor growth, based on the CSC hypothesis,
      and derived using a "chemical reaction" approach. We defined three cell
      subpopulations: CSCs, transit progenitor cells, and differentiated cells. Each
      event related to cell division, differentiation, or death is then modeled as a
      chemical reaction. The resulting set of ordinary differential equations was
      numerically integrated to describe the time evolution of each cell subpopulation
      and the overall tumor growth. The parameter space was explored to identify
      combinations of parameter values that produce biologically feasible and
      consistent scenarios. CONCLUSIONS/SIGNIFICANCE: Certain kinetic relationships
      apparently must be satisfied to sustain solid tumor growth and to maintain an
      approximate constant fraction of CSCs in the tumor lower than 0.01 (as
      experimentally observed): (a) the rate of symmetrical and asymmetrical CSC
      renewal must be in the same order of magnitude; (b) the intrinsic rate of renewal
      and differentiation of progenitor cells must be half an order of magnitude higher
      than the corresponding intrinsic rates for cancer stem cells; (c) the rates of
      apoptosis of the CSC, transit amplifying progenitor (P) cells, and terminally
      differentiated (D) cells must be progressively higher by approximately one order
      of magnitude. Simulation results were consistent with reports that have suggested
      that encouraging CSC differentiation could be an effective therapeutic strategy
      for fighting cancer in addition to selective killing or inhibition of symmetric
      division of CSCs.

PMID- 22363396
TI  - HBV-related hepatocellular carcinoma susceptibility gene KIF1B is not associated
      with development of chronic hepatitis B.
AB  - BACKGROUND: A recent genome-wide association study has identified a new
      susceptibility locus, kinesin family member 1B gene (KIF1B), strongly associated
      with progression from chronic hepatitis B (CHB) to hepatitis B virus-related
      hepatocellular carcinoma (HCC) in Chinese population, this study was carried out
      to explore the role of the genetic variants in KIF1B in the development of
      chronic hepatitis B. METHODOLOGY/PRINCIPAL FINDINGS: Three KIF1B polymorphisms
      (rs8019, rs17401924, and rs17401966) were selected and genotyped in 473 CHB
      patients and 580 controls with no history of CHB. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by logistic regression model. None of
      these three SNPs showed association with CHBs after adjusting for age and gender.
      Equivalence-based method analysis confirmed the absence of association. In the
      further haplotype analysis, three common haplotypes were observed in this study
      population, but no significant effect was also found for haplotypes in the
      progression to CHB. CONCLUSIONS/SIGNIFICANCE: This study showed the new locus
      identified for HCC, KIF1B, was not associated with progression to CHB, implying
      distinct genetic susceptibility factor contributes to the progression from
      hepatitis B virus infection to HCC. Nevertheless, further comprehensive analyses
      are warranted to dissect the mechanism.

PMID- 22363397
TI  - A simple stochastic model with environmental transmission explains multi-year
      periodicity in outbreaks of avian flu.
AB  - Avian influenza virus reveals persistent and recurrent outbreaks in North
      American wild waterfowl, and exhibits major outbreaks at 2-8 years intervals in
      duck populations. The standard susceptible-infected- recovered (SIR) framework,
      which includes seasonal migration and reproduction, but lacks environmental
      transmission, is unable to reproduce the multi-periodic patterns of avian
      influenza epidemics. In this paper, we argue that a fully stochastic theory based
      on environmental transmission provides a simple, plausible explanation for the
      phenomenon of multi-year periodic outbreaks of avian flu. Our theory predicts
      complex fluctuations with a dominant period of 2 to 8 years which essentially
      depends on the intensity of environmental transmission. A wavelet analysis of the
      observed data supports this prediction. Furthermore, using master equations and
      van Kampen system-size expansion techniques, we provide an analytical expression
      for the spectrum of stochastic fluctuations, revealing how the outbreak period
      varies with the environmental transmission.

PMID- 22363398
TI  - Which states matter? An application of an intelligent discretization method to
      solve a continuous POMDP in conservation biology.
AB  - When managing populations of threatened species, conservation managers seek to
      make the best conservation decisions to avoid extinction. Making the best
      decision is difficult because the true population size and the effects of
      management are uncertain. Managers must allocate limited resources between
      actively protecting the species and monitoring. Resources spent on monitoring
      reduce expenditure on management that could be used to directly improve species
      persistence. However monitoring may prevent sub-optimal management actions being
      taken as a result of observation error. Partially observable Markov decision
      processes (POMDPs) can optimize management for populations with partial
      detectability, but the solution methods can only be applied when there are few
      discrete states. We use the Continuous U-Tree (CU-Tree) algorithm to discretely
      represent a continuous state space by using only the states that are necessary to
      maintain an optimal management policy. We exploit the compact discretization
      created by CU-Tree to solve a POMDP on the original continuous state space. We
      apply our method to a population of sea otters and explore the trade-off between
      allocating resources to management and monitoring. We show that accurately
      discovering the population size is less important than management for the long
      term survival of our otter population.

PMID- 22363399
TI  - Palmitate promotes the paracrine effects of macrophages on vascular smooth muscle
      cells: the role of bone morphogenetic proteins.
AB  - Saturated fatty acids are known to activate macrophages and induce vascular
      inflammation. Although cytokines from activated macrophage influence other
      vascular cells, the influence of saturated fatty acids on the paracrine effect of
      macrophages is not fully understood yet. Here we examined the impact of palmitate
      on the effect of macrophages on vascular smooth muscle cells (SMCs) and their
      mediators. SMCs proliferation increased significantly after treatment with
      conditioned media from palmitate-stimulated RAW264.7 cells. SMC migration was
      found to be greater after treatment with palmitate-conditioned media. SM alpha
      actin and SM22alpha were decreased in SMCs treated with palmitate-conditioned
      media. When stimulated with palmitate, RAW264.7 cells secreted more bone
      morphogenetic protein (BMP)2 and BMP4 into the cell culture media. SMC
      proliferation, migration, and phenotypic changes were attenuated after treatment
      of neutralizing antibodies against BMPs or knockdown of BMPs with siRNA. The
      influences of these proteins were further confirmed by direct treatment of
      recombinant BMP2 and BMP4 on SMCs. Particularly, the effects of BMPs on SMC
      migration on phenotypic change were obvious, whereas their effect on SMC
      proliferation seemed not significant or modest. In conclusion, palmitate promoted
      macrophages' paracrine effects on SMC proliferation, migration, and phenotypic
      change. The effect of stimulated macrophages was mediated, at least in part, by
      BMP2 and BMP4. These results suggest a novel mechanism linking saturated fatty
      acids and the progression of vascular diseases that is possibly mediated by BMPs
      from macrophages.

PMID- 22363400
TI  - Maternal and fetal placental growth hormone and IGF axis in type 1 diabetic
      pregnancy.
AB  - AIM: Placental growth hormone (PGH) is a major growth hormone in pregnancy and
      acts with Insulin Like Growth Factor I (IGF-I) and Insulin Like Growth Hormone
      Binding Protein 3 (IGFBP3). The aim of this study was to investigate PGH, IGF-I
      and IGFBP3 in non-diabetic (ND) compared to Type 1 Diabetic (T1DM) pregnancies.
      METHODS: This is a prospective study. Maternal samples were obtained from 25 ND
      and 25 T1DM mothers at 36 weeks gestation. Cord blood was obtained after
      delivery. PGH, IGF-I and IGFBP3 were measured using ELISA. RESULTS: There was no
      difference in delivery type, gender of infants or birth weight between groups. In
      T1DM, maternal PGH significantly correlated with ultrasound estimated fetal
      weight (r = 0.4, p = 0.02), birth weight (r = 0.51, p<0.05) and birth weight
      centile (r = 0.41, p = 0.03) PGH did not correlate with HbA1c. Maternal IGF-I was
      lower in T1DM (p = 0.03). Maternal and fetal serum IGFBP3 was higher in T1DM.
      Maternal third trimester T1DM serum had a significant band at 16 kD on western
      blot, which was not present in ND. CONCLUSION: Maternal T1DM PGH correlated with
      both antenatal fetal weight and birth weight, suggesting a significant role for
      PGH in growth in diabetic pregnancy. IGFBP3 is significantly increased in
      maternal and fetal serum in T1DM pregnancies compared to ND controls, which was
      explained by increased proteolysis in maternal but not fetal serum. These results
      suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in T1DM
      pregnancies, which are at higher risk of macrosomia.

PMID- 22363401
TI  - Targeted expression of Cre recombinase provokes placental-specific DNA
      recombination in transgenic mice.
AB  - BACKGROUND: Inadequate placental development is associated with a high incidence
      of early embryonic lethality and serious pregnancy disorders in both humans and
      mice. However, the lack of well-defined trophoblast-specific gene regulatory
      elements has hampered investigations regarding the role of specific genes in
      placental development and fetal growth. PRINCIPAL FINDINGS: By random assembly of
      placental enhancers from two previously characterized genes, trophoblast specific
      protein alpha (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric
      Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the
      highest luciferase activity in cultured human trophoblast cells, in comparison
      with non-trophoblast cell lines. We used this chimeric enhancer arrangement to
      drive the expression of a Cre recombinase transgene in the placentas of
      transgenic mice. Cre transgene expression occurred throughout the placenta but
      not in maternal organs examined or in the fetus. SIGNIFICANCE: In conclusion, we
      have provided both in vitro and in vivo evidence for a novel genetic system to
      achieve placental transgene expression by the use of a chimeric Tpbpa/Ada
      enhancer driven transgene. The availability of this expression vector provides
      transgenic opportunities to direct the production of desired proteins to the
      placenta.

PMID- 22363402
TI  - Constitutive neutrophil apoptosis: regulation by cell concentration via S100 A8/9
      and the MEK-ERK pathway.
AB  - Programmed cell death (PCD) is a fundamental mechanism in tissue and cell
      homeostasis. It was long suggested that apoptosis regulates the cell number in
      diverse cell populations; however no clear mechanism was shown. Neutrophils are
      the short-lived, first-line defense of innate immunity, with an estimated t = 1/2
      of 8 hours and a high turnover rate. Here we first show that spontaneous
      neutrophil constitutive PCD is regulated by cell concentrations. Using a
      proteomic approach, we identified the S100 A8/9 complex, which constitutes
      roughly 40% of cytosolic protein in neutrophils, as mediating this effect. We
      further demonstrate that it regulates cell survival via a signaling mechanism
      involving MEK-ERK via TLR4 and CD11B/CD18. This mechanism is suggested to have a
      fine-tuning role in regulating the neutrophil number in bone marrow, peripheral
      blood, and inflammatory sites.

PMID- 22363404
TI  - Heterosis as investigated in terms of polyploidy and genetic diversity using
      designed Brassica juncea amphiploid and its progenitor diploid species.
AB  - Fixed heterosis resulting from favorable interactions between the genes on their
      homoeologous genomes in an allopolyploid is considered analogous to classical
      heterosis accruing from interactions between homologous chromosomes in
      heterozygous plants of a diploid species. It has been hypothesized that fixed
      heterosis may be one of the causes of low classical heterosis in allopolyploids.
      We used Indian mustard (Brassica juncea, 2n = 36; AABB) as a model system to
      analyze this hypothesis due to ease of its resynthesis from its diploid
      progenitors, B. rapa (2n = 20; AA) and B. nigra (2n = 16; BB). Both forms of
      heterosis were investigated in terms of ploidy level, gene action and genetic
      diversity. To facilitate this, eleven B. juncea genotypes were resynthesized by
      hybridizing ten near inbred lines of B. rapa and nine of B. nigra. Three half
      diallel combinations involving resynthesized B. juncea (11*11) and the
      corresponding progenitor genotypes of B. rapa (10*10) and B. nigra (9*9) were
      evaluated. Genetic diversity was estimated based on DNA polymorphism generated by
      SSR primers. Heterosis and genetic diversity in parental diploid species appeared
      not to predict heterosis and genetic diversity at alloploid level. There was also
      no association between combining ability, genetic diversity and heterosis across
      ploidy. Though a large proportion (0.47) of combinations showed positive values,
      the average fixed heterosis was low for seed yield but high for biomass yield.
      The genetic diversity was a significant contributor to fixed heterosis for
      biomass yield, due possibly to adaptive advantage it may confer on de novo
      alloploids during evolution. Good general/specific combiners at diploid level did
      not necessarily produce good general/specific combiners at amphiploid level. It
      was also concluded that polyploidy impacts classical heterosis indirectly due to
      the negative association between fixed heterosis and classical heterosis.

PMID- 22363403
TI  - A switch in hepatic cortisol metabolism across the spectrum of non alcoholic
      fatty liver disease.
AB  - CONTEXT: Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation
      of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging
      from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and
      cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of
      NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop
      central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in
      most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol
      availability is controlled by enzymes that regenerate cortisol (F) from inactive
      cortisone (E) (11beta-hydroxysteroid dehydrogenase type 1, 11beta-HSD1), or
      inactivate cortisol through A-ring metabolism (5alpha- and 5beta-reductase,
      5alphaR and 5betaR). OBJECTIVE AND METHODS: In vitro studies defined 11beta-HSD1
      expression in normal and NASH liver samples. We then characterised hepatic
      cortisol metabolism in 16 patients with histologically proven NAFLD compared to
      32 obese controls using gas chromatographic analysis of 24 hour urine collection
      and plasma cortisol generation profile following oral cortisone. RESULTS: In
      patients with steatosis 5alphaR activity was increased, with a decrease in
      hepatic 11beta-HSD1 activity. Total cortisol metabolites were increased in this
      group consistent with increased GC production rate. In contrast, in patients with
      NASH, 11beta-HSD1 activity was increased both in comparison to patients with
      steatosis, and controls. Endorsing these findings, 11beta-HSD1 mRNA and
      immunostaining was markedly increased in NASH patients in peri septal hepatocytes
      and within CD68 positive macrophages within inflamed cirrhotic septa. CONCLUSION:
      Patients with hepatic steatosis have increased clearance and decreased hepatic
      regeneration of cortisol and we propose that this may represent a protective
      mechanism to decrease local GC availability to preserve hepatic metabolic
      phenotype. With progression to NASH, increased 11beta-HSD1 activity and
      consequent cortisol regeneration may serve to limit hepatic inflammation.

PMID- 22363405
TI  - Sample reproducibility of genetic association using different multimarker TDTs in
      genome-wide association studies: characterization and a new approach.
AB  - Multimarker Transmission/Disequilibrium Tests (TDTs) are very robust association
      tests to population admixture and structure which may be used to identify
      susceptibility loci in genome-wide association studies. Multimarker TDTs using
      several markers may increase power by capturing high-degree associations.
      However, there is also a risk of spurious associations and power reduction due to
      the increase in degrees of freedom. In this study we show that associations found
      by tests built on simple null hypotheses are highly reproducible in a second
      independent data set regardless the number of markers. As a test exhibiting this
      feature to its maximum, we introduce the multimarker 2-Groups TDT (mTDT(2G)), a
      test which under the hypothesis of no linkage, asymptotically follows a chi2
      distribution with 1 degree of freedom regardless the number of markers. The
      statistic requires the division of parental haplotypes into two groups: disease
      susceptibility and disease protective haplotype groups. We assessed the test
      behavior by performing an extensive simulation study as well as a real-data study
      using several data sets of two complex diseases. We show that mTDT(2G) test is
      highly efficient and it achieves the highest power among all the tests used, even
      when the null hypothesis is tested in a second independent data set. Therefore,
      mTDT(2G) turns out to be a very promising multimarker TDT to perform genome-wide
      searches for disease susceptibility loci that may be used as a preprocessing step
      in the construction of more accurate genetic models to predict individual
      susceptibility to complex diseases.

PMID- 22363406
TI  - The effect of the visual context in the recognition of symbolic gestures.
AB  - BACKGROUND: To investigate, by means of fMRI, the influence of the visual
      environment in the process of symbolic gesture recognition. Emblems are semiotic
      gestures that use movements or hand postures to symbolically encode and
      communicate meaning, independently of language. They often require contextual
      information to be correctly understood. Until now, observation of symbolic
      gestures was studied against a blank background where the meaning and
      intentionality of the gesture was not fulfilled. METHODOLOGY/PRINCIPAL FINDINGS:
      Normal subjects were scanned while observing short videos of an individual
      performing symbolic gesture with or without the corresponding visual context and
      the context scenes without gestures. The comparison between gestures regardless
      of the context demonstrated increased activity in the inferior frontal gyrus, the
      superior parietal cortex and the temporoparietal junction in the right hemisphere
      and the precuneus and posterior cingulate bilaterally, while the comparison
      between context and gestures alone did not recruit any of these regions.
      CONCLUSIONS/SIGNIFICANCE: These areas seem to be crucial for the inference of
      intentions in symbolic gestures observed in their natural context and represent
      an interrelated network formed by components of the putative human neuron mirror
      system as well as the mentalizing system.

PMID- 22363407
TI  - Factors associated with pleurisy in pigs: a case-control analysis of slaughter
      pig data for England and Wales.
AB  - A case-control investigation was undertaken to determine management and health
      related factors associated with pleurisy in slaughter pigs in England and Wales.
      METHODS: The British Pig Executive Pig Health Scheme database of abattoir
      pathology was used to identify 121 case (>10% prevalence of pleurisy on 3 or more
      assessment dates in the preceding 24 months) and 121 control units (<=5%
      prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months).
      Farm data were collected by postal questionnaire. Data from respondents (70 cases
      and 51 controls) were analysed using simple logistic regression models with
      Bonferroni corrections. Limited multivariate analyses were also performed to
      check the robustness of the overall conclusions. RESULTS AND CONCLUSIONS:
      Management factors associated with increased odds of pleurisy included no all-in
      all-out pig flow (OR 9.3, 95% confidence interval [CI]: 3.3-29), rearing of pigs
      with an age difference of >1 month in the same airspace (OR 6.5 [2.8-17]) and
      repeated mixing (OR 2.2 [1.4-3.8]) or moving (OR 2.2 [1.5-3.4]) of pigs during
      the rearing phase. Those associated with decreased odds of pleurisy included
      filling wean-to-finish or grower-to-finish systems with piglets from <=3 sources
      (OR 0.18 [0.07-0.41]) compared to farrow-to-finish systems, cleaning and
      disinfecting of grower (ORs 0.28 [0.13-0.61] and 0.29 [0.13-0.61]) and finisher
      (ORs 0.24 [0.11-0.51] and 0.2 [0.09-0.44]) accommodation between groups, and
      extended down time of grower and finisher accommodation (OR 0.84 [0.75-0.93] and
      0.86 [0.77-0.94] respectively for each additional day of downtime). This study
      demonstrated the value of national-level abattoir pathology data collection
      systems for case control analyses and generated guidance for on-farm
      interventions to help reduce the prevalence of pleurisy in slaughter pigs.

PMID- 22363408
TI  - Novel protein kinase signaling systems regulating lifespan identified by small
      molecule library screening using Drosophila.
AB  - Protein kinase signaling cascades control most aspects of cellular function. The
      ATP binding domains of signaling protein kinases are the targets of most
      available inhibitors. These domains are highly conserved from mammals to flies.
      Herein we describe screening of a library of small molecule inhibitors of protein
      kinases for their ability to increase Drosophila lifespan. We developed an assay
      system which allowed screening using the small amounts of materials normally
      present in commercial chemical libraries. The studies identified 17 inhibitors,
      the majority of which targeted tyrosine kinases associated with the epidermal
      growth factor receptor (EGFR), platelet-derived growth factor (PDGF)/vascular
      endothelial growth factor (VEGF) receptors, G-protein coupled receptor (GPCR),
      Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the
      insulin and insulin-like growth factor (IGFI) receptors. Comparison of the
      protein kinase signaling effects of the inhibitors in vitro defined a consensus
      intracellular signaling profile which included decreased signaling by p38MAPK
      (p38), c-Jun N-terminal kinase (JNK) and protein kinase C (PKC). If confirmed,
      many of these kinases will be novel additions to the signaling cascades known to
      regulate metazoan longevity.

PMID- 22363409
TI  - Are long-term non-progressors very slow progressors? Insights from the Chelsea
      and Westminster HIV cohort, 1988-2010.
AB  - Define and identify long-term non-progressors (LTNP) and HIV controllers (HIC),
      and estimate time until disease progression. LTNP are HIV-1(+) patients who
      maintain stable CD4(+) T-cell counts, with no history of opportunistic infection
      or antiretroviral therapy (ART). HIC are a subset of LTNP who additionally have
      undetectable viraemia. These individuals may provide insights for prophylactic
      and therapeutic development. Records of HIV-1(+) individuals attending Chelsea
      and Westminster Hospital (1988-2010), were analysed. LTNP were defined as: HIV
      1(+) for >7 years; ART-naive; no history of opportunistic infection and normal,
      stable CD4(+) T-cell counts. MIXED procedure in SAS using random intercept model
      identified long-term stable CD4(+) T-cell counts. Survival analysis estimated
      time since diagnosis until disease progression. Subjects exhibiting long-term
      stable CD4(+) T-cell counts with history below the normal range (<450 cells/ul
      blood) were compared to LTNP whose CD4(+) T-cell count always remained normal.
      Within these two groups subjects with HIV-1 RNA load below limit of detection
      (BLD) were identified. Of 14,227 patients, 1,204 were diagnosed HIV-1(+) over 7
      years ago and were ART-naive. Estimated time until disease progression for the
      20% (239) whose CD4(+) T-cell counts remained within the normal range, was 6.2
      years (IQR: 2.0 to 9.6); significantly longer than 4.0 years (IQR: 1.0 to 7.3)
      for patients with historical CD4(+) T-cell count below normal (Logrank chi
      squared = 21.26; p<0.001). Within a subpopulation of 312 asymptomatic patients,
      50 exhibited long-term stable CD4(+) T-cell counts. Of these, 13 were LTNP, one
      of whom met HIC criteria. Of the remaining 37 patients with long-term stable low
      CD4(+) T-cell counts, 3 controlled HIV-1 RNA load BLD. Individuals with stable,
      normal CD4(+) T-cell counts progressed less rapidly than those with low CD4(+) T
      cell counts. Few LTNP and HIC identified in this and other studies, endorse the
      need for universal definitions to facilitate comparison.

PMID- 22363410
TI  - Feasibility of modified surviving sepsis campaign guidelines in a resource
      restricted setting based on a cohort study of severe S. aureus sepsis
      [corrected].
AB  - BACKGROUND: The Surviving Sepsis Campaign (SSC) guidelines describe best practice
      for the management of severe sepsis and septic shock in developed countries, but
      most deaths from sepsis occur where healthcare is not sufficiently resourced to
      implement them. Our objective was to define the feasibility and basis for
      modified guidelines in a resource-restricted setting. METHODS AND FINDINGS: We
      undertook a detailed assessment of sepsis management in a prospective cohort of
      patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital
      in lower-middle income Thailand. We compared their management with the SSC
      guidelines to identify care bundles based on existing capabilities or additional
      activities that could be undertaken at zero or low cost. We identified 72
      patients with severe sepsis or septic shock associated with S. aureus
      bacteraemia, 38 (53%) of who died within 28 days. One third of patients were
      treated in intensive care units (ICUs). Numerous interventions described by the
      SSC guidelines fell within existing capabilities, but their implementation was
      highly variable. Care available to patients on general wards covered the
      fundamental principles of sepsis management, including non-invasive patient
      monitoring, antimicrobial administration and intravenous fluid resuscitation. We
      described two additive care bundles, one for general wards and the second for
      ICUs, that if consistently performed would be predicted to improve outcome from
      severe sepsis. CONCLUSION: It is feasible to implement modified sepsis guidelines
      that are scaled to resource availability, and that could save lives prior to the
      publication of international guidelines for developing countries.

PMID- 22363411
TI  - Using the Guttman scale to define and estimate measurement error in items over
      time: the case of cognitive decline and the meaning of "points lost".
AB  - We used a Guttman model to represent responses to test items over time as an
      approximation of what is often referred to as "points lost" in studies of
      cognitive decline or interventions. To capture this meaning of "point loss", over
      four successive assessments, we assumed that once an item is incorrect, it cannot
      be correct at a later visit. If the loss of a point represents actual decline,
      then failure of an item to fit the Guttman model over time can be considered
      measurement error. This representation and definition of measurement error also
      permits testing the hypotheses that measurement error is constant for items in a
      test, and that error is independent of "true score", which are two key
      consequences of the definition of "measurement error"--and thereby, reliability-
      under Classical Test Theory. We tested the hypotheses by fitting our model to,
      and comparing our results from, four consecutive annual evaluations in three
      groups of elderly persons: a) cognitively normal (NC, N = 149); b) diagnosed with
      possible or probable AD (N = 78); and c) cognitively normal initially and a later
      diagnosis of AD (converters, N = 133). Of 16 items that converged, error-free
      measurement of "cognitive loss" was observed for 10 items in NC, eight in
      converters, and two in AD. We found that measurement error, as we defined it, was
      inconsistent over time and across cognitive functioning levels, violating the
      theory underlying reliability and other psychometric characteristics, and key
      regression assumptions.

PMID- 22363412
TI  - Single Molecule Analysis Research Tool (SMART): an integrated approach for
      analyzing single molecule data.
AB  - Single molecule studies have expanded rapidly over the past decade and have the
      ability to provide an unprecedented level of understanding of biological systems.
      A common challenge upon introduction of novel, data-rich approaches is the
      management, processing, and analysis of the complex data sets that are generated.
      We provide a standardized approach for analyzing these data in the freely
      available software package SMART: Single Molecule Analysis Research Tool. SMART
      provides a format for organizing and easily accessing single molecule data, a
      general hidden Markov modeling algorithm for fitting an array of possible models
      specified by the user, a standardized data structure and graphical user
      interfaces to streamline the analysis and visualization of data. This approach
      guides experimental design, facilitating acquisition of the maximal information
      from single molecule experiments. SMART also provides a standardized format to
      allow dissemination of single molecule data and transparency in the analysis of
      reported data.

PMID- 22363413
TI  - Chikungunya infection in India: results of a prospective hospital based multi
      centric study.
AB  - BACKGROUND: Chikungunya (CHIKV) has recently seen a re-emergence in India with
      high morbidity. However, the epidemiology and disease burden remain largely
      undetermined. A prospective multi-centric study was conducted to evaluate
      clinical, epidemiological and virological features of chikugunya infection in
      patients with acute febrile illness from various geographical regions of India.
      METHODS AND FINDINGS: A total of 540 patients with fever of up to 7 days duration
      were enrolled at Karnataka Institute of Medical Sciences (KIMS), Karnataka
      (South); Sawai Man Singh Medical College (SMS) Rajasthan (West), and All India
      Institute of Medical Sciences (AIIMS) New Delhi (North) from June 2008 to May
      2009. Serum specimens were screened for chikungunya infection concurrently
      through RT-PCR and serology (IgM). Phylogenetic analysis was performed using
      Bioedit and Mega2 programs. Chikungunya infection was detected in 25.37% patients
      by RT-PCR and/or IgM-ELISA. Highest cases were detected in south (49.36%)
      followed by west (16.28%) and north (0.56%) India. A difference in proportion of
      positives by RT-PCR/ELISA with regard to duration of fever was observed (p<0.05).
      Rashes, joint pain/swelling, abdominal pain and vomiting was frequently observed
      among chikungunya confirmed cases (p<0.05). Adults were affected more than
      children. Anti-CHIK antibodies (IgM) were detected for more than 60 days of fever
      onset. Phylogenetic analysis based on E1 gene from KIMS patients (n = 15)
      revealed ~99% homology clustering with Central/East African genotype. An amino
      acid change from lysine to glutamine at position 132 of E1 gene was frequently
      observed among strains infecting children. CONCLUSIONS: The study documented re
      emergence of chikungunya in high frequencies and severe morbidity in south and
      west India but rare in north. The study emphasizes the need for continuous
      surveillance for disease burden using multiple diagnostic tests and also warrants
      the need for an appropriate molecular diagnostic for early detection of
      chikungunya virus.

PMID- 22363415
TI  - Differential expression profile and genetic variants of microRNAs sequences in
      breast cancer patients.
AB  - The technology available for cancer diagnosis and prognosis is not yet
      satisfactory at the molecular level, and requires further improvements. Micro
      RNAs (miRNAs) have been recently reported as useful biomarkers in diseases
      including cancer. We performed a miRNA expression profiling study using
      peripheral blood from breast cancer patients to detect and identify
      characteristic patterns. A total of 100 breast cancer patients and 89 healthy
      patients were recruited for miRNA genotyping and expression profiling. We found
      that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs
      miR-196a2 in postmenopausal patients, may discriminate breast cancer patients
      from healthy individuals. In addition, we found a significant association between
      two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk.
      However, no significant association between the hs-miR-146a gene and breast
      cancer risk was found. In summary, the study demonstrates that peripheral blood
      miRNAs and their expression and genotypic profiles can be developed as biomarkers
      for early diagnosis and prognosis of breast cancer.

PMID- 22363414
TI  - Amplitude reduction and phase shifts of melatonin, cortisol and other circadian
      rhythms after a gradual advance of sleep and light exposure in humans.
AB  - BACKGROUND: The phase and amplitude of rhythms in physiology and behavior are
      generated by circadian oscillators and entrained to the 24-h day by exposure to
      the light-dark cycle and feedback from the sleep-wake cycle. The extent to which
      the phase and amplitude of multiple rhythms are similarly affected during altered
      timing of light exposure and the sleep-wake cycle has not been fully
      characterized. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the phase and
      amplitude of the rhythms of melatonin, core body temperature, cortisol,
      alertness, performance and sleep after a perturbation of entrainment by a gradual
      advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark
      cycle in 14 healthy men. The light-dark cycle consisted either of moderate
      intensity 'room' light (~90-150 lux) or moderate light supplemented with bright
      light (~10,000 lux) for 5 to 8 hours following sleep. After the advance of the
      sleep-wake schedule in moderate light, no significant advance of the melatonin
      rhythm was observed whereas, after bright light supplementation the phase advance
      was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across
      variables. The amplitude of the melatonin rhythm assessed under constant
      conditions was reduced after moderate light by 54% (17-94%) and after bright
      light by 52% (range 12-84%), as compared to the amplitude at baseline in the
      presence of a sleep-wake cycle. Individual differences in amplitude reduction of
      the melatonin rhythm correlated with the amplitude of body temperature, cortisol
      and alertness. CONCLUSIONS/SIGNIFICANCE: Alterations in the timing of the sleep
      wake cycle and associated bright or moderate light exposure can lead to changes
      in phase and reduction of circadian amplitude which are consistent across
      multiple variables but differ between individuals. These data have implications
      for our understanding of circadian organization and the negative health outcomes
      associated with shift-work, jet-lag and exposure to artificial light.

PMID- 22363416
TI  - Schizotypy and behavioural adjustment and the role of neuroticism.
AB  - OBJECTIVE: In the present study the relationship between behavioural adjustment
      following cognitive conflict and schizotypy was investigated using a Stroop
      colour naming paradigm. Previous research has found deficits with behavioural
      adjustment in schizophrenia patients. Based on these findings, we hypothesized
      that individual differences in schizotypy, a personality trait reflecting the
      subclinical expression of the schizophrenia phenotype, would be associated with
      behavioural adjustment. Additionally, we investigated whether such a relationship
      would be explained by individual differences in neuroticism, a non-specific
      measure of negative trait emotionality known to be correlated with schizotypy.
      METHODS: 106 healthy volunteers (mean age: 25.1, 60% females) took part. Post
      conflict adjustment was measured in a computer-based version of the Stroop
      paradigm. Schizotypy was assessed using the Schizotypal Personality Questionnaire
      (SPQ) and Neuroticism using the NEO-FFI. RESULTS: We found a negative correlation
      between schizotypy and post-conflict adjustment (r = -.30, p<.01); this
      relationship remained significant when controlling for effects of neuroticism.
      Regression analysis revealed that particularly the subscale No Close Friends
      drove the effect. CONCLUSION: Previous findings of deficits in cognitive control
      in schizophrenia patients were extended to the subclinical personality expression
      of the schizophrenia phenotype and found to be specific to schizotypal traits
      over and above the effects of negative emotionality.

PMID- 22363417
TI  - Mitochondrial DNA regionalism and historical demography in the extant populations
      of Chirocephalus kerkyrensis (Branchiopoda: Anostraca).
AB  - BACKGROUND: Mediterranean temporary water bodies are important reservoirs of
      biodiversity and host a unique assemblage of diapausing aquatic invertebrates.
      These environments are currently vanishing because of increasing human pressure.
      Chirocephalus kerkyrensis is a fairy shrimp typical of temporary water bodies in
      Mediterranean plain forests and has undergone a substantial decline in number of
      populations in recent years due to habitat loss. We assessed patterns of genetic
      connectivity and phylogeographic history in the seven extant populations of the
      species from Albania, Corfu Is. (Greece), Southern and Central Italy.
      METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sequence variation at two
      mitochondrial DNA genes (Cytochrome Oxidase I and 16s rRNA) in all the known
      populations of C. kerkyrensis. We used multiple phylogenetic, phylogeographic and
      coalescence-based approaches to assess connectivity and historical demography
      across the whole distribution range of the species. C. kerkyrensis is genetically
      subdivided into three main mitochondrial lineages; two of them are geographically
      localized (Corfu Is. and Central Italy) and one encompasses a wide geographic
      area (Albania and Southern Italy). Most of the detected genetic variation (~81%)
      is apportioned among the aforementioned lineages. CONCLUSIONS/SIGNIFICANCE:
      Multiple analyses of mismatch distributions consistently supported both past
      demographic and spatial expansions with the former predating the latter;
      demographic expansions were consistently placed during interglacial warm phases
      of the Pleistocene while spatial expansions were restricted to cold periods.
      Coalescence methods revealed a scenario of past isolation with low levels of gene
      flow in line with what is already known for other co-distributed fairy shrimps
      and suggest drift as the prevailing force in promoting local divergence. We
      recommend that these evolutionary trajectories should be taken in proper
      consideration in any effort aimed at protecting Mediterranean temporary water
      bodies.

PMID- 22363418
TI  - Inflammatory transcriptome profiling of human monocytes exposed acutely to
      cigarette smoke.
AB  - BACKGROUND: Cigarette smoking is responsible for 5 million deaths worldwide each
      year, and is a major risk factor for cardiovascular and lung diseases. Cigarette
      smoke contains a complex mixture of over 4000 chemicals containing 10(15) free
      radicals. Studies show smoke is perceived by cells as an inflammatory and
      xenobiotic stimulus, which activates an immune response. The specific cellular
      mechanisms driving cigarette smoke-induced inflammation and disease are not fully
      understood, although the innate immune system is involved in the pathology of
      smoking related diseases. METHODOLOGY/PRINCIPLE FINDINGS: To address the impact
      of smoke as an inflammagen on the innate immune system, THP-1 cells and Human
      PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8
      and 24 hours. Total RNA was extracted and the transcriptome analysed using
      Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being
      upregulated and 37 downregulated by >=1.5 fold after 8 hours. In PBMCs stimulated
      with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated
      by >=1.5 fold. After 24 hours, the number of genes activated and repressed by
      >=1.5 fold had risen to 311 and 306 respectively. The major pathways that were
      altered are associated with cell survival, such as inducible antioxidants,
      protein chaperone and folding proteins, and the ubiquitin/proteosome pathway.
      CONCLUSIONS: Our results suggest that cigarette smoke causes inflammation and has
      detrimental effects on the metabolism and function of innate immune cells. In
      addition, THP-1 cells provide a genetically stable alternative to primary cells
      for the study of the effects of cigarette smoke on human monocytes.

PMID- 22363420
TI  - Efficacy of infection control interventions in reducing the spread of multidrug
      resistant organisms in the hospital setting.
AB  - Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally,
      but the population-level impact of recommended preventive strategies and the
      relative benefit of individual strategies targeting all MDRO in the hospital
      setting are unclear. To explore the dynamics of MDRO transmission in the
      hospital, we develop a model extending data from clinical individual-level
      studies to quantify the impact of hand hygiene, contact precautions, reducing
      antimicrobial exposure and screening surveillance cultures in decreasing the
      prevalence of MDRO colonization and infection. The effect of an ongoing increase
      in the influx of patients colonized with MDRO into the hospital setting is also
      quantified. We find that most recommended strategies have substantial effect in
      decreasing the prevalence of MDRO over time. However, screening for asymptomatic
      MDRO colonization among patients who are not receiving antimicrobials is of
      minimal value in reducing the spread of MDRO.

PMID- 22363421
TI  - Vocabulary learning in a Yorkshire terrier: slow mapping of spoken words.
AB  - Rapid vocabulary learning in children has been attributed to "fast mapping", with
      new words often claimed to be learned through a single presentation. As reported
      in 2004 in Science a border collie (Rico) not only learned to identify more than
      200 words, but fast mapped the new words, remembering meanings after just one
      presentation. Our research tests the fast mapping interpretation of the Science
      paper based on Rico's results, while extending the demonstration of large
      vocabulary recognition to a lap dog. We tested a Yorkshire terrier (Bailey) with
      the same procedures as Rico, illustrating that Bailey accurately retrieved
      randomly selected toys from a set of 117 on voice command of the owner. Second we
      tested her retrieval based on two additional voices, one male, one female, with
      different accents that had never been involved in her training, again showing she
      was capable of recognition by voice command. Third, we did both exclusion-based
      training of new items (toys she had never seen before with names she had never
      heard before) embedded in a set of known items, with subsequent retention tests
      designed as in the Rico experiment. After Bailey succeeded on exclusion and
      retention tests, a crucial evaluation of true mapping tested items previously
      successfully retrieved in exclusion and retention, but now pitted against each
      other in a two-choice task. Bailey failed on the true mapping task repeatedly,
      illustrating that the claim of fast mapping in Rico had not been proven, because
      no true mapping task had ever been conducted with him. It appears that the task
      called retention in the Rico study only demonstrated success in retrieval by a
      process of extended exclusion.

PMID- 22363419
TI  - Transgene silencing and transgene-derived siRNA production in tobacco plants
      homozygous for an introduced AtMYB90 construct.
AB  - Transgenic tobacco (Nicotiana tabacum) lines were engineered to ectopically over
      express AtMYB90 (PAP2), an R2-R3 Myb gene associated with regulation of
      anthocyanin production in Arabidopsis thaliana. Independently transformed
      transgenic lines, Myb27 and Myb237, accumulated large quantities of anthocyanin,
      generating a dark purple phenotype in nearly all tissues. After self
      fertilization, some progeny of the Myb27 line displayed an unexpected
      pigmentation pattern, with most leaves displaying large sectors of dramatically
      reduced anthocyanin production. The green-sectored 27Hmo plants were all found to
      be homozygous for the transgene and, despite a doubled transgene dosage, to have
      reduced levels of AtMYB90 mRNA. The observed reduction in anthocyanin
      pigmentation and AtMYB90 mRNA was phenotypically identical to the patterns seen
      in leaves systemically silenced for the AtMYB90 transgene, and was associated
      with the presence of AtMYB90-derived siRNA homologous to both strands of a
      portion of the AtMYB90 transcribed region. Activation of transgene silencing in
      the Myb27 line was triggered when the 35S::AtMYB90 transgene dosage was doubled,
      in both Myb27 homozygotes, and in plants containing one copy of each of the
      independently segregating Myb27 and Myb237 transgene loci. Mapping of sequenced
      siRNA molecules to the Myb27 TDNA (including flanking tobacco sequences)
      indicated that the 3' half of the AtMYB90 transcript is the primary target for
      siRNA associated silencing in both homozygous Myb27 plants and in systemically
      silenced tissues. The transgene within the Myb27 line was found to consist of a
      single, fully intact, copy of the AtMYB90 construct. Silencing appears to
      initiate in response to elevated levels of transgene mRNA (or an aberrant product
      thereof) present within a subset of leaf cells, followed by spread of the
      resulting small RNA to adjacent leaf tissues and subsequent amplification of
      siRNA production.

PMID- 22363422
TI  - Novel transgenic mice for inducible gene overexpression in pancreatic cells
      define glucocorticoid receptor-mediated regulations of beta cells.
AB  - Conditional gene deletion in specific cell populations has helped the
      understanding of pancreas development. Using this approach, we have shown that
      deleting the glucocorticoid receptor (GR) gene in pancreatic precursor cells
      leads to a doubled beta-cell mass. Here, we provide genetic tools that permit a
      temporally and spatially controlled expression of target genes in pancreatic
      cells using the Tetracycline inducible system. To efficiently target the
      Tetracycline transactivator (tTA) in specific cell populations, we generated
      Bacterial Artificial Chromosomes (BAC) transgenic mice expressing the improved
      Tetracycline transactivator (itTA) either in pancreatic progenitor cells
      expressing the transcription factor Pdx1 (BAC-Pdx1-itTA), or in beta cells
      expressing the insulin1 gene (BAC-Ins1-itTA). In the two transgenic models, itTA
      mediated activation of reporter genes was efficient and subject to regulation by
      Doxycycline (Dox). The analysis of a tetracycline-regulated LacZ reporter gene
      shows that in BAC-Pdx1-itTA mice, itTA is expressed from embryonic (E) day 11.5
      in all pancreatic precursor cells. In the adult pancreas, itTA is active in
      mature beta, delta cells and in few acinar cells. In BAC-Ins1-itTA mice tTA is
      active from E13.5 and is restricted to beta cells in fetal and adult pancreas. In
      both lines, tTA activity was suppressed by Dox treatment and re-induced after Dox
      removal. Using these transgenic lines, we overexpressed the GR in selective
      pancreatic cell populations and found that overexpression in precursor cells
      altered adult beta-cell fraction but not glucose tolerance. In contrast, GR
      overexpression in mature beta cells did not alter beta-cell fraction but impaired
      glucose tolerance with insufficient insulin secretion. In conclusion, these new
      itTA mouse models will allow fine-tuning of gene expression to investigate gene
      function in pancreatic biology and help us understand how glucocorticoid
      signaling affects on the long-term distinct aspects of beta-cell biology.

PMID- 22363423
TI  - Reconsidering association testing methods using single-variant test statistics as
      alternatives to pooling tests for sequence data with rare variants.
AB  - Association tests that pool minor alleles into a measure of burden at a locus
      have been proposed for case-control studies using sequence data containing rare
      variants. However, such pooling tests are not robust to the inclusion of neutral
      and protective variants, which can mask the association signal from risk
      variants. Early studies proposing pooling tests dismissed methods for locus-wide
      inference using nonnegative single-variant test statistics based on unrealistic
      comparisons. However, such methods are robust to the inclusion of neutral and
      protective variants and therefore may be more useful than previously appreciated.
      In fact, some recently proposed methods derived within different frameworks are
      equivalent to performing inference on weighted sums of squared single-variant
      score statistics. In this study, we compared two existing methods for locus-wide
      inference using nonnegative single-variant test statistics to two widely cited
      pooling tests under more realistic conditions. We established analytic results
      for a simple model with one rare risk and one rare neutral variant, which
      demonstrated that pooling tests were less powerful than even Bonferroni-corrected
      single-variant tests in most realistic situations. We also performed simulations
      using variants with realistic minor allele frequency and linkage disequilibrium
      spectra, disease models with multiple rare risk variants and extensive neutral
      variation, and varying rates of missing genotypes. In all scenarios considered,
      existing methods using nonnegative single-variant test statistics had power
      comparable to or greater than two widely cited pooling tests. Moreover, in
      disease models with only rare risk variants, an existing method based on the
      maximum single-variant Cochran-Armitage trend chi-square statistic in the locus
      had power comparable to or greater than another existing method closely related
      to some recently proposed methods. We conclude that efficient locus-wide
      inference using single-variant test statistics should be reconsidered as a useful
      framework for devising powerful association tests in sequence data with rare
      variants.

PMID- 22363424
TI  - Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and
      steatosis.
AB  - MicroRNAs (miRNAs) are small RNA molecules that function to modulate the
      expression of target genes, playing important roles in a wide range of
      physiological and pathological processes. The miRNAs in body fluids have received
      considerable attention as potential biomarkers of various diseases. In this
      study, we compared the changes of the plasma miRNA expressions by acute liver
      injury (hepatocellular injury or cholestasis) and chronic liver injury
      (steatosis, steatohepatitis and fibrosis) using rat models made by the
      administration of chemicals or special diets. Using miRNA array analysis, we
      found that the levels of a large number of miRNAs (121-317 miRNAs) were increased
      over 2-fold and the levels of a small number of miRNAs (6-35 miRNAs) were
      decreased below 0.5-fold in all models except in a model of cholestasis caused by
      bile duct ligation. Interestingly, the expression profiles were different between
      the models, and the hierarchical clustering analysis discriminated between the
      acute and chronic liver injuries. In addition, miRNAs whose expressions were
      typically changed in each type of liver injury could be specified. It is notable
      that, in acute liver injury models, the plasma level of miR-122, the most
      abundant miRNA in the liver, was more quickly and dramatically increased than the
      plasma aminotransferase level, reflecting the extent of hepatocellular injury.
      This study demonstrated that the plasma miRNA profiles could reflect the types of
      liver injury (e.g. acute/chronic liver injury or hepatocellular
      injury/cholestasis/steatosis/steatohepatitis/fibrosis) and identified the miRNAs
      that could be specific and sensitive biomarkers of liver injury.

PMID- 22363425
TI  - Hospital and community ampicillin-resistant Enterococcus faecium are
      evolutionarily closely linked but have diversified through niche adaptation.
AB  - BACKGROUND: Ampicillin-resistant Enterococcus faecium (ARE) has emerged as a
      nosocomial pathogen. Here, we quantified ARE carriage in different community
      sources and determined genetic relatedness with hospital ARE. METHODS AND
      RESULTS: ARE was recovered from rectal swabs of 24 of 79 (30%) dogs, 11 of 85
      (13%) cats and 0 of 42 horses and from 3 of 40 (8%) faecal samples of non
      hospitalized humans receiving amoxicillin. Multi-locus Sequence Typing revealed
      21 sequence types (STs), including 5 STs frequently associated with hospital
      acquired infections. Genes previously found to be enriched in hospital ARE, such
      as IS16, orf903, orf905, orf907, were highly prevalent in community ARE (>=79%),
      while genes with a proposed role in pathogenesis, such as esp, hyl and ecbA, were
      found rarely (<=5%) in community isolates. Comparative genome analysis of 2
      representative dog isolates revealed that the dog strain of ST192 was
      evolutionarily closely linked to two previously sequenced hospital ARE, but had,
      based on gene content, more genes in common with the other, evolutionarily more
      distantly related, dog strain (ST266). CONCLUSION: ARE were detected in dogs,
      cats and sporadically in healthy humans, with evolutionary linkage to hospital
      ARE. Yet, their accessory genome has diversified, probably as a result of niche
      adaptation.

PMID- 22363426
TI  - The burden of invasive bacterial infections in Pemba, Zanzibar.
AB  - BACKGROUND: We conducted a surveillance study to determine the leading causes of
      bloodstream infection in febrile patients seeking treatment at three district
      hospitals in Pemba Island, Zanzibar, Tanzania, an area with low malaria
      transmission. METHODS: All patients above two months of age presenting to
      hospital with fever were screened, and blood was collected for microbiologic
      culture and malaria testing. Bacterial sepsis and malaria crude incidence rates
      were calculated for a one-year period and were adjusted for study participation
      and diagnostic sensitivity of blood culture. RESULTS: Blood culture was performed
      on 2,209 patients. Among them, 166 (8%) samples yielded bacterial growth; 87 (4%)
      were considered as likely contaminants; and 79 (4%) as pathogenic bacteria. The
      most frequent pathogenic bacteria isolated were Salmonella Typhi (n = 46; 58%),
      followed by Streptococcus pneumoniae (n = 12; 15%). The crude bacteremia rate was
      6/100,000 but when adjusted for potentially missed cases the rate may be as high
      as 163/100,000. Crude and adjusted rates for S. Typhi infections and malaria were
      4 and 110/100,000 and 4 and 47/100,000, respectively. Twenty three (51%), 22
      (49%) and 22 (49%) of the S. Typhi isolates were found to be resistant toward
      ampicillin, chloramphenicol and cotrimoxazole, respectively. Multidrug resistance
      (MDR) against the three antimicrobials was detected in 42% of the isolates.
      CONCLUSIONS: In the presence of very low malaria incidence we found high rates of
      S. Typhi and S. pneumoniae infections on Pemba Island, Zanzibar. Preventive
      measures such as vaccination could reduce the febrile disease burden.

PMID- 22363427
TI  - Incidence and risk of QTc interval prolongation among cancer patients treated
      with vandetanib: a systematic review and meta-analysis.
AB  - BACKGROUND: Vandetanib is a multikinase inhibitor that is under assessment for
      the treatment of various cancers. QTc interval prolongation is one of the major
      adverse effects of this drug, but the reported incidence varies substantially
      among clinical trials. We performed a systematic review and meta-analysis to
      obtain a better understanding in the risk of QTc interval prolongation among
      cancer patients administered vandetanib. METHODOLOGY AND PRINCIPAL FINDINGS:
      Eligible studies were phase II and III prospective clinical trials that involved
      cancer patients who were prescribed vandetanib 300 mg/d and that included data on
      QTc interval prolongation. The overall incidence and risk of QTc interval
      prolongation were calculated using random-effects or fixed-effects models,
      depending on the heterogeneity of the included studies. Nine trials with 2,188
      patients were included for the meta-analysis. The overall incidence of all-grade
      and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4%) and 3.7%
      (8.1-30.4%), respectively, among non-thyroid cancer patients, and 18.0% (10.7
      28.6%) and 12.0% (4.5-28.0%), respectively, among thyroid cancer patients.
      Patients with thyroid cancer who had longer treatment duration also had a higher
      incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71), than
      patients who had non-thyroid cancer. Vandetanib was associated with a
      significantly increased risk of all-grade QTc interval prolongation with overall
      Peto odds ratios of 7.26 (4.36-12.09) and 5.70 (3.09-10.53) among patients with
      non-thyroid cancer and thyroid cancer, respectively, compared to the controls.
      CONCLUSIONS/SIGNIFICANCE: Treatment with vandetanib is associated with a
      significant increase in the overall incidence and risk of QTc interval
      prolongation. Different cancer types and treatment durations may affect the risk
      of developing high-grade QTc interval prolongation.

PMID- 22363428
TI  - Transcriptional silencing of the Wnt-antagonist DKK1 by promoter methylation is
      associated with enhanced Wnt signaling in advanced multiple myeloma.
AB  - The Wnt/beta-catenin pathway plays a crucial role in the pathogenesis of various
      human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine
      activation of canonical Wnt signaling promotes proliferation and dissemination,
      while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells
      contributes to osteolytic bone disease by inhibiting osteoblast differentiation.
      Since DKK1 itself is a target of TCF/beta-catenin mediated transcription, these
      findings suggest that DKK1 is part of a negative feedback loop in MM and may act
      as a tumor suppressor. In line with this hypothesis, we show here that DKK1
      expression is low or undetectable in a subset of patients with advanced MM as
      well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt
      pathway activation, evidenced by nuclear accumulation of beta-catenin, which in
      turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1
      promoter revealed CpG island methylation in several MM cell lines as well as in
      MM cells from patients with advanced MM. Moreover, demethylation of the DKK1
      promoter restores DKK1 expression, which results in inhibition of beta
      catenin/TCF-mediated gene transcription in MM lines. Taken together, our data
      identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing
      in advanced stage MM, which may play an important role in the progression of MM
      by unleashing Wnt signaling.

PMID- 22363429
TI  - Molecular cloning and characterization of two genes encoding dihydroflavonol-4
      reductase from Populus trichocarpa.
AB  - Dihydroflavonol 4-reductase (DFR, EC 1.1.1.219) is a rate-limited enzyme in the
      biosynthesis of anthocyanins and condensed tannins (proanthocyanidins) that
      catalyzes the reduction of dihydroflavonols to leucoanthocyanins. In this study,
      two full-length transcripts encoding for PtrDFR1 and PtrDFR2 were isolated from
      Populus trichocarpa. Sequence alignment of the two PtrDFRs with other known DFRs
      reveals the homology of these genes. The expression profile of PtrDFRs was
      investigated in various tissues of P. trichocarpa. To determine their functions,
      two PtrDFRs were overexpressed in tobacco (Nicotiana tabacum) via Agrobacterium
      mediated transformation. The associated color change in the flowers was observed
      in all 35S:PtrDFR1 lines, but not in 35S:PtrDFR2 lines. Compared to the wild-type
      control, a significantly higher accumulation of anthocyanins was detected in
      transgenic plants harboring the PtrDFR1. Furthermore, overexpressing PtrDFR1 in
      Chinese white poplar (P. tomentosa Carr.) resulted in a higher accumulation of
      both anthocyanins and condensed tannins, whereas constitutively expressing
      PtrDFR2 only improved condensed tannin accumulation, indicating the potential
      regulation of condensed tannins by PtrDFR2 in the biosynthetic pathway in
      poplars.

PMID- 22363430
TI  - Altered perceptual sensitivity to kinematic invariants in Parkinson's disease.
AB  - Ample evidence exists for coupling between action and perception in
      neurologically healthy individuals, yet the precise nature of the internal
      representations shared between these domains remains unclear. One experimentally
      derived view is that the invariant properties and constraints characterizing
      movement generation are also manifested during motion perception. One prominent
      motor invariant is the "two-third power law," describing the strong relation
      between the kinematics of motion and the geometrical features of the path
      followed by the hand during planar drawing movements. The two-thirds power law
      not only characterizes various movement generation tasks but also seems to
      constrain visual perception of motion. The present study aimed to assess whether
      motor invariants, such as the two thirds power law also constrain motion
      perception in patients with Parkinson's disease (PD). Patients with PD and age
      matched controls were asked to observe the movement of a light spot rotating on
      an elliptical path and to modify its velocity until it appeared to move most
      uniformly. As in previous reports controls tended to choose those movements close
      to obeying the two-thirds power law as most uniform. Patients with PD displayed a
      more variable behavior, choosing on average, movements closer but not equal to a
      constant velocity. Our results thus demonstrate impairments in how the two-thirds
      power law constrains motion perception in patients with PD, where this
      relationship between velocity and curvature appears to be preserved but scaled
      down. Recent hypotheses on the role of the basal ganglia in motor timing may
      explain these irregularities. Alternatively, these impairments in perception of
      movement may reflect similar deficits in motor production.

PMID- 22363431
TI  - Scaling effects and spatio-temporal multilevel dynamics in epileptic seizures.
AB  - Epileptic seizures are one of the most well-known dysfunctions of the nervous
      system. During a seizure, a highly synchronized behavior of neural activity is
      observed that can cause symptoms ranging from mild sensual malfunctions to the
      complete loss of body control. In this paper, we aim to contribute towards a
      better understanding of the dynamical systems phenomena that cause seizures.
      Based on data analysis and modelling, seizure dynamics can be identified to
      possess multiple spatial scales and on each spatial scale also multiple time
      scales. At each scale, we reach several novel insights. On the smallest spatial
      scale we consider single model neurons and investigate early-warning signs of
      spiking. This introduces the theory of critical transitions to excitable systems.
      For clusters of neurons (or neuronal regions) we use patient data and find
      oscillatory behavior and new scaling laws near the seizure onset. These scalings
      lead to substantiate the conjecture obtained from mean-field models that a Hopf
      bifurcation could be involved near seizure onset. On the largest spatial scale we
      introduce a measure based on phase-locking intervals and wavelets into seizure
      modelling. It is used to resolve synchronization between different regions in the
      brain and identifies time-shifted scaling laws at different wavelet scales. We
      also compare our wavelet-based multiscale approach with maximum linear cross
      correlation and mean-phase coherence measures.

PMID- 22363432
TI  - Classification of activity engagement in individuals with severe physical
      disabilities using signals of the peripheral nervous system.
AB  - Communication barriers often result in exclusion of children and youth with
      disabilities from activities and social settings that are essential to their
      psychosocial development. In particular, difficulties in describing their
      experiences of activities and social settings hinder our understanding of the
      factors that promote inclusion and participation of this group of individuals. To
      address this specific communication challenge, we examined the feasibility of
      developing a language-free measure of experience in youth with severe physical
      disabilities. To do this, we used the activity of the peripheral nervous system
      to detect patterns of psychological arousal associated with activities requiring
      different patterns of cognitive/affective and interpersonal involvement (activity
      engagement). We demonstrated that these signals can differentiate among patterns
      of arousal associated with these activities with high accuracy (two levels: 81%,
      three levels: 74%). These results demonstrate the potential for development of a
      real-time, motor- and language-free measure for describing the experiences of
      children and youth with disabilities.

PMID- 22363433
TI  - Crystal structure of TDRD3 and methyl-arginine binding characterization of TDRD3,
      SMN and SPF30.
AB  - SMN (Survival motor neuron protein) was characterized as a dimethyl-arginine
      binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3) and
      SPF30 (Splicing factor 30 kDa) were found to bind to various methyl-arginine
      proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be
      a transcriptional coactivator, and its transcriptional activity is dependent on
      its ability to bind arginine-methylated histone marks. In this study, we
      systematically characterized the binding specificity and affinity of the Tudor
      domains of these three proteins quantitatively. Our results show that TDRD3
      preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a
      very promiscuous effector molecule, which recognizes different arginine
      containing sequence motifs and preferentially binds symmetrical dimethylated
      arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR
      motif sequences in our library. In addition, we also reported high-resolution
      crystal structures of the Tudor domain of TDRD3 in complex with two small
      molecules, which occupy the aromatic cage of TDRD3.

PMID- 22363434
TI  - Array-comparative genomic hybridization reveals loss of SOCS6 is associated with
      poor prognosis in primary lung squamous cell carcinoma.
AB  - BACKGROUND: Primary tumor recurrence commonly occurs after surgical resection of
      lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC
      recurrence. METHODS: We used array comparative genomic hybridization (aCGH) to
      identify genes affected by copy number alterations that may be involved in SCC
      recurrence. Training and test sets of resected primary lung SCC were assembled.
      aCGH was used to determine genomic copy number in a training set of 62 primary
      lung SCCs (28 with recurrence and 34 with no evidence of recurrence) and the
      altered copy number of candidate genes was confirmed by quantitative PCR (qPCR).
      An independent test set of 72 primary lung SCCs (20 with recurrence and 52 with
      no evidence of recurrence) was used for biological validation. mRNA expression of
      candidate genes was studied using qRT-PCR. Candidate gene promoter methylation
      was evaluated using methylation microarrays and Sequenom EpiTYPER analysis.
      RESULTS: 18q22.3 loss was identified by aCGH as being significantly associated
      with recurrence (p = 0.038). Seven genes within 18q22.3 had aCGH copy number loss
      associated with recurrence but only SOCS6 copy number was both technically
      replicated by qPCR and biologically validated in the test set. SOCS6 copy number
      loss correlated with reduced mRNA expression in the study samples and in the
      samples with copy number loss, there was a trend for increased methylation,
      albeit non-significant. Overall survival was significantly poorer in patients
      with SOCS6 loss compared to patients without SOCS6 loss in both the training (30
      vs. 43 months, p = 0.023) and test set (27 vs. 43 months, p = 0.010). CONCLUSION:
      Reduced copy number and mRNA expression of SOCS6 are associated with disease
      recurrence in primary lung SCC and may be useful prognostic biomarkers.

PMID- 22363435
TI  - Stimulus-specific activation and actin dependency of distinct, spatially
      separated ERK1/2 fractions in A7r5 smooth muscle cells.
AB  - A proliferative response of smooth muscle cells to activation of extracellular
      signal regulated kinases 1 and 2 (ERK1/2) has been linked to cardiovascular
      disease. In fully differentiated smooth muscle, however, ERK1/2 activation can
      also regulate contraction. Here, we use A7r5 smooth muscle cells, stimulated with
      12-deoxyphorbol 13-isobutylate 20-acetate (DPBA) to induce cytoskeletal
      remodeling or fetal calf serum (FCS) to induce proliferation, to identify factors
      that determine the outcomes of ERK1/2 activation in smooth muscle. Knock down
      experiments, immunoprecipitation and proximity ligation assays show that the
      ERK1/2 scaffold caveolin-1 mediates ERK1/2 activation in response to DPBA, but
      not FCS, and that ERK1/2 is released from caveolin-1 upon DPBA, but not FCS,
      stimulation. Conversely, ERK1/2 associated with the actin cytoskeleton is
      significantly reduced after FCS, but not DPBA stimulation, as determined by
      Triton X fractionation. Furthermore, cytochalasin treatment inhibits DPBA, but
      not FCS-induced ERK1/2 phosphorylation, indicating that the actin cytoskeleton is
      not only a target but also is required for ERK1/2 activation. Our results show
      that (1) at least two ERK1/2 fractions are regulated separately by specific
      stimuli, and that (2) the association of ERK1/2 with the actin cytoskeleton
      regulates the outcome of ERK1/2 signaling.

PMID- 22363436
TI  - Signaling networks associated with AKT activation in non-small cell lung cancer
      (NSCLC): new insights on the role of phosphatydil-inositol-3 kinase.
AB  - Aberrant activation of PI3K/AKT signalling represents one of the most common
      molecular alterations in lung cancer, though the relative contribution of the
      single components of the cascade to the NSCLC development is still poorly
      defined. In this manuscript we have investigated the relationship between
      expression and genetic alterations of the components of the PI3K/AKT pathway
      [KRAS, the catalytic subunit of PI3K (p110alpha), PTEN, AKT1 and AKT2] and the
      activation of AKT in 107 surgically resected NSCLCs and have analyzed the
      existing relationships with clinico-pathologic features. Expression analysis was
      performed by immunohistochemistry on Tissue Micro Arrays (TMA); mutation analysis
      was performed by DNA sequencing; copy number variation was determined by FISH. We
      report that activation of PI3K/AKT pathway in Italian NSCLC patients is
      associated with high grade (G3-G4 compared with G1-G2; n = 83; p<0.05) and more
      advanced disease (TNM stage III vs. stages I and II; n = 26; p<0.05). In
      addition, we found that PTEN loss (41/104, 39%) and the overexpression of
      p110alpha (27/92, 29%) represent the most frequent aberration observed in NSCLCs.
      Less frequent molecular lesions comprised the overexpression of AKT2 (18/83, 22%)
      or AKT1 (17/96, 18%), and KRAS mutation (7/63, 11%). Our results indicate that,
      among all genes, only p110alpha overexpression was significantly associated to
      AKT activation in NSCLCs (p = 0.02). Manipulation of p110alpha expression in lung
      cancer cells carrying an active PI3K allele (NCI-H460) efficiently reduced
      proliferation of NSCLC cells in vitro and tumour growth in vivo. Finally, RNA
      profiling of lung epithelial cells (BEAS-2B) expressing a mutant allele of PIK3
      (E545K) identified a network of transcription factors such as MYC, FOS and HMGA1,
      not previously recognised to be associated with aberrant PI3K signalling in lung
      cancer.

PMID- 22363437
TI  - Modelling the influence of foot-and-mouth disease vaccine antigen stability and
      dose on the bovine immune response.
AB  - Foot and mouth disease virus causes a livestock disease of significant global
      socio-economic importance. Advances in its control and eradication depend
      critically on improvements in vaccine efficacy, which can be best achieved by
      better understanding the complex within-host immunodynamic response to
      inoculation. We present a detailed and empirically parametrised dynamical
      mathematical model of the hypothesised immune response in cattle, and explore its
      behaviour with reference to a variety of experimental observations relating to
      foot and mouth immunology. The model system is able to qualitatively account for
      the observed responses during in-vivo experiments, and we use it to gain insight
      into the incompletely understood effect of single and repeat inoculations of
      differing dosage using vaccine formulations of different structural stability.

PMID- 22363438
TI  - Dynamics of seed-borne rice endophytes on early plant growth stages.
AB  - Bacterial endophytes are ubiquitous to virtually all terrestrial plants. With the
      increasing appreciation of studies that unravel the mutualistic interactions
      between plant and microbes, we increasingly value the beneficial functions of
      endophytes that improve plant growth and development. However, still little is
      known on the source of established endophytes as well as on how plants select
      specific microbial communities to establish associations. Here, we used
      cultivation-dependent and -independent approaches to assess the endophytic
      bacterrial community of surface-sterilized rice seeds, encompassing two
      consecutive rice generations. We isolated members of nine bacterial genera. In
      particular, organisms affiliated with Stenotrophomonas maltophilia and
      Ochrobactrum spp. were isolated from both seed generations. PCR-based denaturing
      gradient gel electrophoresis (PCR-DGGE) of seed-extracted DNA revealed that
      approximately 45% of the bacterial community from the first seed generation was
      found in the second generation as well. In addition, we set up a greenhouse
      experiment to investigate abiotic and biotic factors influencing the endophytic
      bacterial community structure. PCR-DGGE profiles performed with DNA extracted
      from different plant parts showed that soil type is a major effector of the
      bacterial endophytes. Rice plants cultivated in neutral-pH soil favoured the
      growth of seed-borne Pseudomonas oryzihabitans and Rhizobium radiobacter, whereas
      Enterobacter-like and Dyella ginsengisoli were dominant in plants cultivated in
      low-pH soil. The seed-borne Stenotrophomonas maltophilia was the only conspicuous
      bacterial endophyte found in plants cultivated in both soils. Several members of
      the endophytic community originating from seeds were observed in the rhizosphere
      and surrounding soils. Their impact on the soil community is further discussed.

PMID- 22363439
TI  - Composition, diversity, and origin of the bacterial community in grass carp
      intestine.
AB  - Gut microbiota has become an integral component of the host, and received
      increasing attention. However, for many domestic animals, information on the
      microbiota is insufficient and more effort should be exerted to manage the
      gastrointestinal bacterial community. Understanding the factors that influence
      the composition of microbial community in the host alimentary canal is essential
      to manage or improve the microbial community composition. In the present study,
      16S rRNA gene sequence-based comparisons of the bacterial communities in the
      grass carp (Ctenopharyngodon idellus) intestinal contents and fish culture
      associated environments are performed. The results show that the fish intestinal
      microbiota harbors many cellulose-decomposing bacteria, including sequences
      related to Anoxybacillus, Leuconostoc, Clostridium, Actinomyces, and Citrobacter.
      The most abundant bacterial operational taxonomic units (OTUs) in the grass carp
      intestinal content are those related to feed digestion. In addition, the
      potential pathogens and probiotics are important members of the intestinal
      microbiota. Further analyses show that grass carp intestine holds a core
      microbiota composed of Proteobacteria, Firmicutes, and Actinobacteria. The
      comparison analyses reveal that the bacterial community in the intestinal
      contents is most similar to those from the culture water and sediment. However,
      feed also plays significant influence on the composition of gut microbiota.

PMID- 22363440
TI  - cis-Expression QTL analysis of established colorectal cancer risk variants in
      colon tumors and adjacent normal tissue.
AB  - Genome-wide association studies (GWAS) have identified 19 risk variants
      associated with colorectal cancer. As most of these risk variants reside outside
      the coding regions of genes, we conducted cis-expression quantitative trait loci
      (cis-eQTL) analyses to investigate possible regulatory functions on the
      expression of neighboring genes. Forty microsatellite stable and CpG island
      methylator phenotype-negative colorectal tumors and paired adjacent normal colon
      tissues were used for genome-wide SNP and gene expression profiling. We found
      that three risk variants (rs10795668, rs4444235 and rs9929218, using near perfect
      proxies rs706771, rs11623717 and rs2059252, respectively) were significantly
      associated (FDR q-value <=0.05) with expression levels of nearby genes (<2 Mb up-
      or down-stream). We observed an association between the low colorectal cancer
      risk allele (A) for rs10795668 at 10p14 and increased expression of ATP5C1 (q =
      0.024) and between the colorectal cancer high risk allele (C) for rs4444235 at
      14q22.2 and increased expression of DLGAP5 (q = 0.041), both in tumor samples.
      The colorectal cancer low risk allele (A) for rs9929218 at 16q22.1 was associated
      with a significant decrease in expression of both NOL3 (q = 0.017) and DDX28 (q =
      0.046) in the adjacent normal colon tissue samples. Of the four genes, DLGAP5 and
      NOL3 have been previously reported to play a role in colon carcinogenesis and
      ATP5C1 and DDX28 are mitochondrial proteins involved in cellular metabolism and
      division, respectively. The combination of GWAS findings, prior functional
      studies, and the cis-eQTL analyses described here suggest putative functional
      activities for three of the colorectal cancer GWAS identified risk loci as
      regulating the expression of neighboring genes.

PMID- 22363441
TI  - Selective serotonin reuptake inhibitor use is associated with right ventricular
      structure and function: the MESA-right ventricle study.
AB  - PURPOSE: Serotonin and the serotonin transporter have been implicated in the
      development of pulmonary hypertension (PH). Selective serotonin reuptake
      inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use
      on right ventricular (RV) structure and function are unknown. We hypothesized
      that SSRI use would be associated with RV morphology in a large cohort without
      cardiovascular disease (N = 4114). METHODS: SSRI use was determined by medication
      inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination.
      RV measures were assessed via cardiac magnetic resonance imaging. The cross
      sectional relationship between SSRI use and each RV measure was assessed using
      multivariable linear regression; analyses for RV mass and end-diastolic volume
      (RVEDV) were stratified by sex. RESULTS: After adjustment for multiple covariates
      including depression and left ventricular measures, SSRI use was associated with
      larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02
      mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08
      g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p
      = 0.001). SSRI use may have been associated with larger RVEDV among women and
      larger RV end-systolic volume in both sexes. CONCLUSIONS: SSRI use was associated
      with higher RVSV in cardiovascular disease-free individuals and, among men,
      greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at
      risk for) RV dysfunction and the role of sex in modifying this relationship
      warrant further study.

PMID- 22363442
TI  - A symmetric dual feedback system provides a robust and entrainable oscillator.
AB  - Many organisms have evolved molecular clocks to anticipate daily changes in their
      environment. The molecular mechanisms by which the circadian clock network
      produces sustained cycles have extensively been studied and transcriptional
      translational feedback loops are common structures to many organisms. Although a
      simple or single feedback loop is sufficient for sustained oscillations,
      circadian clocks implement multiple, complicated feedback loops. In general,
      different types of feedback loops are suggested to affect the robustness and
      entrainment of circadian rhythms. To reveal the mechanism by which such a complex
      feedback system evolves, we quantify the robustness and light entrainment of four
      competing models: the single, semi-dual, dual, and redundant feedback models. To
      extract the global properties of those models, all plausible kinetic parameter
      sets that generate circadian oscillations are searched to characterize their
      oscillatory features. To efficiently perform such analyses, we used the two-phase
      search (TPS) method as a fast and non-biased search method and quasi
      multiparameter sensitivity (QMPS) as a fast and exact measure of robustness to
      uncertainty of all kinetic parameters.So far the redundant feedback model has
      been regarded as the most robust oscillator, but our extensive analysis corrects
      or overcomes this hypothesis. The dual feedback model, which is employed in
      biology, provides the most robust oscillator to multiple parameter perturbations
      within a cell and most readily entrains to a wide range of light-dark cycles. The
      kinetic symmetry between the dual loops and their coupling via a protein complex
      are found critically responsible for robust and entrainable oscillations. We
      first demonstrate how the dual feedback architecture with kinetic symmetry
      evolves out of many competing feedback systems.

PMID- 22363443
TI  - Predicting tropical dry forest successional attributes from space: is the key
      hidden in image texture?
AB  - Biodiversity conservation and ecosystem-service provision will increasingly
      depend on the existence of secondary vegetation. Our success in achieving these
      goals will be determined by our ability to accurately estimate the structure and
      diversity of such communities at broad geographic scales. We examined whether the
      texture (the spatial variation of the image elements) of very high-resolution
      satellite imagery can be used for this purpose. In 14 fallows of different ages
      and one mature forest stand in a seasonally dry tropical forest landscape, we
      estimated basal area, canopy cover, stem density, species richness, Shannon
      index, Simpson index, and canopy height. The first six attributes were also
      estimated for a subset comprising the tallest plants. We calculated 40 texture
      variables based on the red and the near infrared bands, and EVI and NDVI, and
      selected the best-fit linear models describing each vegetation attribute based on
      them. Basal area (R(2) = 0.93), vegetation height and cover (0.89), species
      richness (0.87), and stand age (0.85) were the best-described attributes by two
      variable models. Cross validation showed that these models had a high predictive
      power, and most estimated vegetation attributes were highly accurate. The success
      of this simple method (a single image was used and the models were linear and
      included very few variables) rests on the principle that image texture reflects
      the internal heterogeneity of successional vegetation at the proper scale. The
      vegetation attributes best predicted by texture are relevant in the face of two
      of the gravest threats to biosphere integrity: climate change and biodiversity
      loss. By providing reliable basal area and fallow-age estimates, image-texture
      analysis allows for the assessment of carbon sequestration and diversity loss
      rates. New and exciting research avenues open by simplifying the analysis of the
      extent and complexity of successional vegetation through the spatial variation of
      its spectral information.

PMID- 22363444
TI  - Rescue of recent virulent and avirulent field strains of bluetongue virus by
      reverse genetics.
AB  - Since 1998, Bluetongue virus (BTV)-serotypes 1, 2, 4, 9, and 16 have invaded
      European countries around the Mediterranean Basin. In 2006, a huge BT-outbreak
      started after incursion of BTV-serotype 8 (BTV8) in North-Western Europe. More
      recently, BTV6 and BTV11 were reported in North-Western Europe in 2008. These
      latter strains are closely related to live-attenuated vaccine, whereas BTV8 is
      virulent and can induce severe disease in ruminants, including cattle. In
      addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which
      was recognized as a new serotype of BTV (BTV25). The (re-)emergency of known and
      unknown BTV-serotypes needs a rapid response to supply effective vaccines, and
      research to study this phenomenon. Recently, orbivirus research achieved an
      important breakthrough by the establishment of reverse genetics for BTV1. Here,
      reverse genetics for two recent BTV strains representing virulent BTV8 and
      avirulent BTV6 was developed. For this purpose, extensive sequencing of full
      genomes was performed, resulting in the consensus sequences of BTV8/net07 and
      BTV6/net08. The recovery of 'synthetic BTV', respectively rgBTV8 and rgBTV6,
      completely from T7-derived RNA transcripts was confirmed by silent mutations by
      which these 'synthetic BTVs' could be genetically distinguished from wild type
      BTV, respectively wtBTV6 and wtBTV8. The in vitro and in vivo properties of
      rgBTV6 or rgBTV8 were comparable to the properties of their parent strains. The
      asymptomatic or avirulent properties of rgBTV6 and the virulence of rgBTV8 were
      confirmed by experimental infection of sheep. Reverse genetics of the vaccine
      related BTV6 provides a perfect start to develop new generations of BT-vaccines.
      Reverse genetics of the virulent BTV8 will accelerate research on the special
      features of BTV8, like transmission by species of Culicoides in a moderate
      climate, transplacental transmission, and pathogenesis in cattle.

PMID- 22363445
TI  - CCN2/connective tissue growth factor is essential for pericyte adhesion and
      endothelial basement membrane formation during angiogenesis.
AB  - CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that
      regulates cell adhesion, migration, and survival. CCN2 is best known for its
      ability to promote fibrosis by mediating the ability of transforming growth
      factor beta (TGFbeta) to induce excess extracellular matrix production. In
      addition to its role in pathological processes, CCN2 is required for
      chondrogenesis. CCN2 is also highly expressed during development in endothelial
      cells, suggesting a role in angiogenesis. The potential role of CCN2 in
      angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have
      been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2
      is required for stable association and retention of pericytes by endothelial
      cells. PDGF signaling and the establishment of the endothelial basement membrane
      are required for pericytes recruitment and retention. CCN2 induced PDGF-B
      expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in
      mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the
      production of endothelial basement membrane components in vitro, and was required
      for their expression in vivo. Overall, these results highlight CCN2 as an
      essential mediator of vascular remodeling by regulating endothelial-pericyte
      interactions. Although most studies of CCN2 function have focused on effects of
      CCN2 overexpression on the interstitial extracellular matrix, the results
      presented here show that CCN2 is required for the normal production of vascular
      basement membranes.

PMID- 22363446
TI  - Origins of the tumor microenvironment: quantitative assessment of adipose-derived
      and bone marrow-derived stroma.
AB  - To meet the requirements for rapid tumor growth, a complex array of non
      neoplastic cells are recruited to the tumor microenvironment. These cells
      facilitate tumor development by providing matrices, cytokines, growth factors, as
      well as vascular networks for nutrient and waste exchange, however their precise
      origins remain unclear. Through multicolored tissue transplant procedures; we
      have quantitatively determined the contribution of bone marrow-derived and
      adipose-derived cells to stromal populations within syngeneic ovarian and breast
      murine tumors. Our results indicate that subpopulations of tumor-associated
      fibroblasts (TAFs) are recruited from two distinct sources. The majority of
      fibroblast specific protein (FSP) positive and fibroblast activation protein
      (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located
      in bone marrow sources, whereas most vascular and fibrovascular stroma
      (pericytes, alpha-SMA(+) myofibroblasts, and endothelial cells) originates from
      neighboring adipose tissue. These results highlight the capacity for tumors to
      utilize multiple sources of structural cells in a systematic and discriminative
      manner.

PMID- 22363447
TI  - Human tumor cell proliferation evaluated using manganese-enhanced MRI.
AB  - BACKGROUND: Tumor cell proliferation can depend on calcium entry across the cell
      membrane. As a first step toward the development of a non-invasive test of the
      extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor
      cell uptake of a calcium surrogate, Mn(2+) [measured with manganese-enhanced MRI
      (MEMRI)], is linked to proliferation rate in vitro. METHODOLOGY/PRINCIPAL
      FINDINGS: Proliferation rates were determined in vitro in three different human
      tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate
      carcinoma. Cells growing at different average proliferation rates were exposed to
      1 mM MnCl(2) for one hour and then thoroughly washed. MEMRI R(1) values
      (longitudinal relaxation rates), which have a positive linear relationship with
      Mn(2+) concentration, were then determined from cell pellets. Cell cycle
      distributions were determined using propidium iodide staining and flow cytometry.
      All three lines showed Mn(2+)-induced increases in R(1) compared to cells not
      exposed to Mn(2+). C918 and PC-3 cells each showed a significant, positive
      correlation between MEMRI R(1) values and proliferation rate (p<=0.005), while
      OCM-1 cells showed no significant correlation. Preliminary, general modeling of
      these positive relationships suggested that pellet R(1) for the PC-3 cells, but
      not for the C918 cells, could be adequately described by simply accounting for
      changes in the distribution of the cell cycle-dependent subpopulations in the
      pellet. CONCLUSIONS/SIGNIFICANCE: These data clearly demonstrate the tumor-cell
      dependent nature of the relationship between proliferation and calcium influx,
      and underscore the usefulness of MEMRI as a non-invasive method for investigating
      this link. MEMRI is applicable to study tumors in vivo, and the present results
      raise the possibility of evaluating proliferation parameters of some tumor types
      in vivo using MEMRI.

PMID- 22363449
TI  - Identification of new splice sites used for generation of rev transcripts in
      human immunodeficiency virus type 1 subtype C primary isolates.
AB  - The HIV-1 primary transcript undergoes a complex splicing process by which more
      than 40 different spliced RNAs are generated. One of the factors contributing to
      HIV-1 splicing complexity is the multiplicity of 3' splice sites (3'ss) used for
      generation of rev RNAs, with two 3'ss, A4a and A4b, being most commonly used, a
      third site, A4c, used less frequently, and two additional sites, A4d and A4e,
      reported in only two and one isolates, respectively. HIV-1 splicing has been
      analyzed mostly in subtype B isolates, and data on other group M clades are
      lacking. Here we examine splice site usage in three primary isolates of subtype
      C, the most prevalent clade in the HIV-1 pandemic, by using an in vitro infection
      assay of peripheral blood mononuclear cells. Viral spliced RNAs were identified
      by RT-PCR amplification using a fluorescently-labeled primer and software
      analyses and by cloning and sequencing the amplified products. The results
      revealed that splice site usage for generation of rev transcripts in subtype C
      differs from that reported for subtype B, with most rev RNAs using two previously
      unreported 3'ss, one located 7 nucleotides upstream of 3'ss A4a, designated A4f,
      preferentially used by two isolates, and another located 14 nucleotides upstream
      of 3'ss A4c, designated A4g, preferentially used by the third isolate. A new 5'
      splice site, designated D2a, was also identified in one virus. Usage of the newly
      identified splice sites is consistent with sequence features commonly found in
      subtype C viruses. These results show that splice site usage may differ between
      HIV-1 subtypes.

PMID- 22363448
TI  - Role for a novel Usher protein complex in hair cell synaptic maturation.
AB  - The molecular mechanisms underlying hair cell synaptic maturation are not well
      understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G
      protein coupled receptor 1 (VLGR1) have been implicated in the development of
      cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a
      role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause
      Usher syndrome, characterized by congenital deafness, vestibular dysfunction and
      retinitis pigmentosa. Here we show developmental expression of these Usher
      proteins in afferent spiral ganglion neurons and hair cell synapses. We identify
      a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of
      CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we
      performed morphological and quantitative analysis of the neuronal fibers and
      their synapses in the Clrn1-/- mouse, which was generated by incomplete deletion
      of the gene. These mice showed a delay in neuronal/synaptic maturation by both
      immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames
      waltzer(av3J) mice also suggests a delay in hair cell synaptogenesis.
      Collectively, these results show that, in addition to the well documented role
      for Usher proteins in stereocilia development, Usher protein complexes comprised
      of specific protein isoforms likely function in synaptic maturation as well.

PMID- 22363450
TI  - Curcumin induces cell death in esophageal cancer cells through modulating Notch
      signaling.
AB  - BACKGROUND: Curcumin inhibits the growth of esophageal cancer cell lines;
      however, the mechanism of action is not well understood. It is becoming
      increasingly clear that aberrant activation of Notch signaling has been
      associated with the development of esophageal cancer. Here, we have determined
      that curcumin inhibits esophageal cancer growth via a mechanism mediated through
      the Notch signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      show that curcumin treatment resulted in a dose and time dependent inhibition of
      proliferation and colony formation in esophageal cancer cell lines. Furthermore,
      curcumin treatment induced apoptosis through caspase 3 activation, confirmed by
      an increase in the ratio of Bax to Bcl2. Cell cycle analysis demonstrated that
      curcumin treatment induced cell death and down regulated cyclin D1 levels.
      Curcumin treatment also resulted in reduced number and size of esophagospheres.
      Furthermore, curcumin treatment led to reduced Notch-1 activation, expression of
      Jagged-1 and its downstream target Hes-1. This reduction in Notch-1 activation
      was determined to be due to the down-regulation of critical components of the
      gamma-secretase complex proteins such as Presenilin 1 and Nicastrin. The
      combination of a known gamma-secretase inhibitor DAPT and curcumin further
      decreased proliferation and induced apoptosis in esophageal cancer cells.
      Finally, curcumin treatment down-regulate the expressions of Notch-1 specific
      microRNAs miR-21 and miR-34a, and upregulated tumor suppressor let-7a miRNA.
      CONCLUSION/SIGNIFICANCE: Curcumin is a potent inhibitor of esophageal cancer
      growth that targets the Notch-1 activating gamma-secretase complex proteins.
      These data suggest that Notch signaling inhibition is a novel mechanism of action
      for curcumin during therapeutic intervention in esophageal cancers.

PMID- 22363451
TI  - TSC1/2 signaling complex is essential for peripheral naive CD8+ T cell survival
      and homeostasis in mice.
AB  - The PI3K-Akt-mTOR pathway plays crucial roles in regulating both innate and
      adaptive immunity. However, the role of TSC1, a critical negative regulator of
      mTOR, in peripheral T cell homeostasis remains elusive. With T cell-specific Tsc1
      conditional knockout (Tsc1 KO) mice, we found that peripheral naive CD8(+) T
      cells but not CD4(+) T cells were severely reduced. Tsc1 KO naive CD8(+) T cells
      showed profound survival defect in an adoptive transfer model and in culture with
      either stimulation of IL-7 or IL-15, despite comparable CD122 and CD127
      expression between control and KO CD8(+) T cells. IL-7 stimulated phosphorylation
      of Akt(S473) was diminished in Tsc1 KO naive CD8(+)T cells due to hyperactive
      mTOR-mediated feedback suppression on PI3K-AKT signaling. Furthermore, impaired
      Foxo1/Foxo3a phosphorylation and increased pro-apoptotic Bim expression in Tsc1
      KO naive CD8(+)T cells were observed upon stimulation of IL-7. Collectively, our
      study suggests that TSC1 plays an essential role in regulating peripheral naive
      CD8(+) T cell homeostasis, possible via an mTOR-Akt-FoxO-Bim signaling pathway.

PMID- 22363452
TI  - Efficient induction of extrinsic cell death by dandelion root extract in human
      chronic myelomonocytic leukemia (CMML) cells.
AB  - BACKGROUND: Chronic Myelomonocytic Leukemia (CMML) is a heterogeneous disease
      that is not only hard to diagnose and classify, but is also highly resistant to
      treatment. Available forms of therapy for this disease have not shown significant
      effects and patients rapidly develop resistance early on in therapy. These
      factors lead to the very poor prognosis observed with CMML patients, with median
      survival duration between 12 and 24 months after diagnosis. This study is
      therefore centered around evaluating the selective efficacy of a natural extract
      from dandelion roots, in inducing programmed cell death in aggressive and
      resistant CMML cell lines. METHODOLOGY/PRINCIPAL FINDINGS: To confirm the
      induction of programmed cell death in three human CMML cell lines, nuclear
      condensation and externalization of the phosphatidylserine, two main
      characteristics of apoptosis, were detected using Hoechst staining and annexin-V
      binding assay. The induction of another mode of cell death, autophagy, was
      determined using a monodansylcadaverine (MDC) stain, to detect the formation of
      autophagy vacuoles. The results from this study indicate that Dandelion Root
      Extract (DRE) is able to efficiently and selectively induce apoptosis and
      autophagy in these cell lines in a dose and time dependent manner, with no
      significant toxicity on non-cancerous peripheral blood mononuclear cells. More
      importantly, we observed early activation of initiator caspase-8, which led to
      mitochondrial destabilization and the induction of autophagy, suggesting that DRE
      acts through the extrinsic pathway of apoptosis. The inability of DRE to induce
      apoptosis in dominant-negative FADD cells, confirms the mechanism of action of
      DRE in in vitro models of CMML. CONCLUSION: The results from this study indicate
      that natural products, in particular Dandelion Root Extract, have great
      potential, as non-toxic and effective alternatives to conventional modes of
      chemotherapy available today.

PMID- 22363453
TI  - Factors associated with self-reported HBV vaccination among HIV-negative MSM
      participating in an online sexual health survey: a cross-sectional study.
AB  - BACKGROUND: A substantial proportion of men who have sex with men (MSM) in the
      United States remain unvaccinated against hepatitis B. We sought to understand
      which factors are associated with vaccination among HIV-negative MSM.
      METHODOLOGY/PRINCIPAL FINDINGS: Data were from a 2010 web-based survey of adult
      MSM. We calculated the prevalence of self-reported hepatitis B vaccination among
      1,052 HIV-negative or HIV-untested men who knew their hepatitis B vaccination
      status, and used multivariate logistic regression to determine associated
      factors. 679 (64.5%) MSM reported being vaccinated. Younger men were more likely
      to report being vaccinated than older men, and there was a significant
      interaction between age and history of hepatitis B testing. Men with at least
      some college education were at least 2.1 times as likely to be vaccinated as men
      with a high school education or less (95% CI = 1.4-3.1). Provider recommendation
      for vaccination (aOR = 4.2, 95% CI = 2.4-7.4) was also significantly associated
      with receipt of vaccination. CONCLUSIONS/SIGNIFICANCE: Providers should assess
      sexual histories of male patients and offer those patients with male sex partners
      testing for hepatitis infection and vaccinate susceptible patients. There may be
      particular opportunities for screening and vaccination among older and more
      socioeconomically disadvantaged MSM.

PMID- 22363454
TI  - Molecular approach to the identification of fish in the South China Sea.
AB  - BACKGROUND: DNA barcoding is one means of establishing a rapid, accurate, and
      cost-effective system for the identification of species. It involves the use of
      short, standard gene targets to create sequence profiles of known species against
      sequences of unknowns that can be matched and subsequently identified. The Fish
      Barcode of Life (FISH-BOL) campaign has the primary goal of gathering DNA barcode
      records for all the world's fish species. As a contribution to FISH-BOL, we
      examined the degree to which DNA barcoding can discriminate marine fishes from
      the South China Sea. METHODOLOGY/PRINCIPAL FINDINGS: DNA barcodes of cytochrome
      oxidase subunit I (COI) were characterized using 1336 specimens that belong to
      242 species fishes from the South China Sea. All specimen provenance data
      (including digital specimen images and geospatial coordinates of collection
      localities) and collateral sequence information were assembled using Barcode of
      Life Data System (BOLD; www.barcodinglife.org). Small intraspecific and large
      interspecific differences create distinct genetic boundaries among most species.
      In addition, the efficiency of two mitochondrial genes, 16S rRNA (16S) and
      cytochrome b (cytb), and one nuclear ribosomal gene, 18S rRNA (18S), was also
      evaluated for a few select groups of species. CONCLUSIONS/SIGNIFICANCE: The
      present study provides evidence for the effectiveness of DNA barcoding as a tool
      for monitoring marine biodiversity. Open access data of fishes from the South
      China Sea can benefit relative applications in ecology and taxonomy.

PMID- 22363455
TI  - Yersinia pestis lineages in Mongolia.
AB  - BACKGROUND: Whole genome sequencing allowed the development of a number of high
      resolution sequence based typing tools for Yersinia (Y.) pestis. The application
      of these methods on isolates from most known foci worldwide and in particular
      from China and the Former Soviet Union has dramatically improved our
      understanding of the population structure of this species. In the current view,
      Y. pestis including the non or moderate human pathogen Y. pestis subspecies
      microtus emerged from Yersinia pseudotuberculosis about 2,600 to 28,600 years ago
      in central Asia. The majority of central Asia natural foci have been
      investigated. However these investigations included only few strains from
      Mongolia. METHODOLOGY/PRINCIPAL FINDINGS: Clustered Regularly Interspaced Short
      Prokaryotic Repeats (CRISPR) analysis and Multiple-locus variable number of
      tandem repeats (VNTR) analysis (MLVA) with 25 loci was performed on 100 Y. pestis
      strains, isolated from 37 sampling areas in Mongolia. The resulting data were
      compared with previously published data from more than 500 plague strains, 130 of
      which had also been previously genotyped by single nucleotide polymorphism (SNP)
      analysis. The comparison revealed six main clusters including the three microtus
      biovars Ulegeica, Altaica, and Xilingolensis. The largest cluster comprises 78
      isolates, with unique and new genotypes seen so far in Mongolia only. Typing of
      selected isolates by key SNPs was used to robustly assign the corresponding
      clusters to previously defined SNP branches. CONCLUSIONS/SIGNIFICANCE: We show
      that Mongolia hosts the most recent microtus clade (Ulegeica). Interestingly no
      representatives of the ancestral Y. pestis subspecies pestis nodes previously
      identified in North-western China were identified in this study. This observation
      suggests that the subsequent evolution steps within Y. pestis pestis did not
      occur in Mongolia. Rather, Mongolia was most likely re-colonized by more recent
      clades coming back from China contemporary of the black death pandemic, or more
      recently in the past 600 years.

PMID- 22363456
TI  - A robust co-localisation measurement utilising z-stack image intensity
      similarities for biological studies.
AB  - BACKGROUND: Co-localisation is a widely used measurement in immunohistochemical
      analysis to determine if fluorescently labelled biological entities, such as
      cells, proteins or molecules share a same location. However the measurement of co
      localisation is challenging due to the complex nature of such fluorescent images,
      especially when multiple focal planes are captured. The current state-of-art co
      localisation measurements of 3-dimensional (3D) image stacks are biased by noise
      and cross-overs from non-consecutive planes. METHOD: In this study, we have
      developed Co-localisation Intensity Coefficients (CICs) and Co-localisation
      Binary Coefficients (CBCs), which uses rich z-stack data from neighbouring focal
      planes to identify similarities between image intensities of two and potentially
      more fluorescently-labelled biological entities. This was developed using z-stack
      images from murine organotypic slice cultures from central nervous system tissue,
      and two sets of pseudo-data. A large amount of non-specific cross-over situations
      are excluded using this method. This proposed method is also proven to be robust
      in recognising co-localisations even when images are polluted with a range of
      noises. RESULTS: The proposed CBCs and CICs produce robust co-localisation
      measurements which are easy to interpret, resilient to noise and capable of
      removing a large amount of false positivity, such as non-specific cross-overs.
      Performance of this method of measurement is significantly more accurate than
      existing measurements, as determined statistically using pseudo datasets of known
      values. This method provides an important and reliable tool for fluorescent 3D
      neurobiological studies, and will benefit other biological studies which measure
      fluorescence co-localisation in 3D.

PMID- 22363457
TI  - Bacterial vaginosis (BV) candidate bacteria: associations with BV and behavioural
      practices in sexually-experienced and inexperienced women.
AB  - BACKGROUND: In recent years several new fastidious bacteria have been identified
      that display a high specificity for BV; however no previous studies have
      comprehensively assessed the behavioural risk associations of these bacterial
      vaginosis-candidate organisms (BV-COs). METHODS: We examined the associations
      between 8 key previously described BV-COs and BV status established by Nugent's
      score (NS). We also examined the sexual practices associated with each BV-CO. We
      incorporated 2 study populations: 193 from a sexually-inexperienced university
      population and 146 from a highly sexually-active clinic population. Detailed
      behavioural data was collected by questionnaire and vaginal smears were scored by
      the Nugent method. Stored samples were tested by quantitative PCR assays for the
      8 BV-COs: Atopobium vaginae, Gardnerella vaginalis, Leptotrichia spp.,
      Megasphaera type I, Sneathia spp., and the Clostridia-like bacteria BVAB1, BVAB2
      and BVAB3. Associations between BV-COs and BV and behaviours were examined by
      univariate and multivariable analyses. RESULTS: On univariate analysis, all BV
      COs were more common in BV compared to normal flora. However, only Megasphaera
      type I, BVAB2, A. vaginae and G. vaginalis were significantly independently
      associated with BV by multivariable analysis. Six of the eight BV-COs
      (Megasphaera type I, BVAB2, BVAB3, Sneathia, Leptotrichia and G. vaginalis) were
      rare or absent in sexually-unexposed women, and demonstrated increasing odds of
      detection with increasing levels of sexual activity and/or numbers of lifetime
      sexual partners. Only G. vaginalis and A. vaginae were commonly detected in
      sexually-unexposed women. Megasphaera type I was independently associated with
      women-who-have-sex-with women (WSW) and lifetime sexual partner numbers, while
      unprotected penile-vaginal-sex was associated with BVAB2 detection by
      multivariate analysis. CONCLUSIONS: Four of eight key BV-COs were significantly
      associated with BV after adjusting for the presence of other BV-COs. The majority
      of BV-COs were absent or rare in sexually-unexposed women, and associated with
      increasing sexual exposure, suggesting potential sexual transmission of BV-COs.

PMID- 22363458
TI  - The new school absentees reporting system for pandemic influenza A/H1N1 2009
      infection in Japan.
AB  - OBJECTIVE: To evaluate the new Japanese School Absentees Reporting System for
      Infectious Disease (SARSID) for pandemic influenza A/H1N1 2009 infection in
      comparison with the National epidemiological Surveillance of Infectious Disease
      (NESID). METHODS: We used data of 53,223 students (97.7%) in Takamatsu city
      Japan. Data regarding school absentees in SARSID was compared with that in NESID
      from Oct 13, 2009 to Jan 12, 2010. RESULTS: Similar trends were observed both in
      SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought
      to be more sensitive than that in NESID. CONCLUSION: The epidemic trend for
      influenza among school-aged children could be easily and rapidly assessed by
      SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend
      of influenza.

PMID- 22363459
TI  - DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort.
AB  - BACKGROUND: Genetic evidence implicates the DISC1 gene in the etiology of a
      number of mental illnesses. Previously, we have reported association between
      DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale
      (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth
      Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome
      wide association analysis has recently been performed. METHODOLOGY: In the
      present study, we re-analyzed the genome-wide association data with regard to
      these two measures of psychosis proneness, conditioning on our previous DISC1
      observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals
      provided phenotype and genotype data. No markers were significant at the genome
      wide level. However, several genes with biological relevance to mental illnesses
      were highlighted through loci displaying suggestive evidence for association (>=3
      SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT,
      MED13L, TMCO7, TTN, and the micro RNA MIR620. CONCLUSIONS: By conditioning a
      previous genome-wide association study on DISC1, we have been able to identify
      eight genes as associating to psychosis proneness. Further, these molecules
      predominantly link to the DISC1 pathway, strengthening the evidence for the role
      of this gene network in the etiology of mental illness. The use of quantitative
      measures of psychosis proneness in a large population cohort will make these
      findings, once verified; more generalized to a broad selection of disorders
      related to psychoses and psychosis proneness.

PMID- 22363460
TI  - Pleiotropic roles of a ribosomal protein in Dictyostelium discoideum.
AB  - The cell cycle phase at starvation influences post-starvation differentiation and
      morphogenesis in Dictyostelium discoideum. We found that when expressed in
      Saccharomyces cerevisiae, a D. discoideum cDNA that encodes the ribosomal protein
      S4 (DdS4) rescues mutations in the cell cycle genes cdc24, cdc42 and bem1. The
      products of these genes affect morphogenesis in yeast via a coordinated moulding
      of the cytoskeleton during bud site selection. D. discoideum cells that over- or
      under-expressed DdS4 did not show detectable changes in protein synthesis but
      displayed similar developmental aberrations whose intensity was graded with the
      extent of over- or under-expression. This suggested that DdS4 might influence
      morphogenesis via a stoichiometric effect--specifically, by taking part in a
      multimeric complex similar to the one involving Cdc24p, Cdc42p and Bem1p in
      yeast. In support of the hypothesis, the S. cerevisiae proteins Cdc24p, Cdc42p
      and Bem1p as well as their D. discoideum cognates could be co-precipitated with
      antibodies to DdS4. Computational analysis and mutational studies explained these
      findings: a C-terminal domain of DdS4 is the functional equivalent of an SH3
      domain in the yeast scaffold protein Bem1p that is central to constructing the
      bud site selection complex. Thus in addition to being part of the ribosome, DdS4
      has a second function, also as part of a multi-protein complex. We speculate that
      the existence of the second role can act as a safeguard against perturbations to
      ribosome function caused by spontaneous variations in DdS4 levels.

PMID- 22363461
TI  - Regulatory design governing progression of population growth phases in bacteria.
AB  - It has long been noted that batch cultures inoculated with resting bacteria
      exhibit a progression of growth phases traditionally labeled lag, exponential,
      pre-stationary and stationary. However, a detailed molecular description of the
      mechanisms controlling the transitions between these phases is lacking. A core
      circuit, formed by a subset of regulatory interactions involving five global
      transcription factors (FIS, HNS, IHF, RpoS and GadX), has been identified by
      correlating information from the well- established transcriptional regulatory
      network of Escherichia coli and genome-wide expression data from cultures in
      these different growth phases. We propose a functional role for this circuit in
      controlling progression through these phases. Two alternative hypotheses for
      controlling the transition between the growth phases are first, a continuous
      graded adjustment to changing environmental conditions, and second, a
      discontinuous hysteretic switch at critical thresholds between growth phases. We
      formulate a simple mathematical model of the core circuit, consisting of
      differential equations based on the power-law formalism, and show by mathematical
      and computer-assisted analysis that there are critical conditions among the
      parameters of the model that can lead to hysteretic switch behavior, which--if
      validated experimentally--would suggest that the transitions between different
      growth phases might be analogous to cellular differentiation. Based on these
      provocative results, we propose experiments to test the alternative hypotheses.

PMID- 22363462
TI  - Tracking down abstract linguistic meaning: neural correlates of spatial frame of
      reference ambiguities in language.
AB  - This functional magnetic resonance imaging (fMRI) study investigates a crucial
      parameter in spatial description, namely variants in the frame of reference
      chosen. Two frames of reference are available in European languages for the
      description of small-scale assemblages, namely the intrinsic (or object-oriented)
      frame and the relative (or egocentric) frame. We showed participants a sentence
      such as "the ball is in front of the man", ambiguous between the two frames, and
      then a picture of a scene with a ball and a man--participants had to respond by
      indicating whether the picture did or did not match the sentence. There were two
      blocks, in which we induced each frame of reference by feedback. Thus for the
      crucial test items, participants saw exactly the same sentence and the same
      picture but now from one perspective, now the other. Using this method, we were
      able to precisely pinpoint the pattern of neural activation associated with each
      linguistic interpretation of the ambiguity, while holding the perceptual stimuli
      constant. Increased brain activity in bilateral parahippocampal gyrus was
      associated with the intrinsic frame of reference whereas increased activity in
      the right superior frontal gyrus and in the parietal lobe was observed for the
      relative frame of reference. The study is among the few to show a distinctive
      pattern of neural activation for an abstract yet specific semantic parameter in
      language. It shows with special clarity the nature of the neural substrate
      supporting each frame of spatial reference.

PMID- 22363463
TI  - Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse
      midbrain.
AB  - Due to their correlation with major human neurological diseases, dopaminergic
      neurons are some of the most studied neuronal subtypes. Mesencephalic
      dopaminergic (mDA) differentiation requires the activation of a cascade of
      transcription factors, among which play a crucial role the nuclear receptor Nurr1
      and the paired-like homeodomain 3, Pitx3. During development the expression of
      Nurr1 precedes that of Pitx3 and those of typical dopaminergic markers such as
      tyrosine hydroxylase (TH) and dopamine Transporter (DAT) that are directly
      regulated by Nurr1. Interestingly we have previously demonstrated that Nurr1 RNA
      silencing reduced Pitx3 transcripts, leading to the hypothesis that Nurr1 may
      control Pitx3 expression.Here we show that Nurr1 overexpression up-regulates that
      of Pitx3 in a dose-dependent manner by binding to a non-canonical NBRE consensus
      sequence, located at the 5' site of the gene. Interestingly, this sequence shows
      the same effect as the canonical one in promoting gene translation, and its
      deletion abolishes the ability of Nurr1 to sustain reporter gene expression.
      Moreover, we show that there is a direct interaction between Nurr1 and the Pitx3
      gene promoter in dopaminergic cell cultures and midbrain embryonic tissue.
      Altogether, our results suggest that the regulation of Pitx3 by Nurr1 may be an
      essential event controlling the development and function of mDA neurons.

PMID- 22363464
TI  - Genetic variants in telomere-maintenance genes and bladder cancer risk.
AB  - Telomeres are critical in maintaining genomic stability. Genetic variants in
      telomere pathway genes may affect telomere and telomerase function, and
      subsequently cancer risk. We evaluated 126 SNPs from 10 genes related to telomere
      regulation in relation to bladder cancer risk. Five SNPs, 4 from TEP1 gene and 1
      from PINX1 gene, were found to be highly significant (P<0.01). Out of these, the
      most significant association was found in rs2228041 of TEP1 (OR 1.66, 95% CI 1.19
      2.31) while rs1469557 of PINX1 had a protective effect (OR 0.75, 95% CI 0.61
      0.93). Haplotype analysis showed that a TEP1 haplotype consisting of the variant
      alleles of 7 SNPs exhibited a 2.28 fold increased risk (95% CI 1.13-4.60). We
      then performed cumulative analysis of multiple risk variants, as well as
      Classification and Regression Tree (CART) to look for gene-gene interactions. In
      cumulative effect analysis, the group with 4-5 risk variants had an OR of 2.57
      (95% CI = 1.62-4.09) versus the reference group with 0 risk variants. The CART
      analysis categorized individuals into five subgroups with different bladder
      cancer risk profiles based on their distinct genotype background. To our
      knowledge, this is one of the largest, most comprehensive studies on bladder
      cancer risk concerning telomere-regulating pathway gene SNPs and our results
      support that genetic variations of telomere maintenance modulate bladder cancer
      risk individually and jointly.

PMID- 22363465
TI  - The settlement of Madagascar: what dialects and languages can tell us.
AB  - The dialects of Madagascar belong to the Greater Barito East group of the
      Austronesian family and it is widely accepted that the Island was colonized by
      Indonesian sailors after a maritime trek that probably took place around 650 CE.
      The language most closely related to Malagasy dialects is Maanyan, but Malay is
      also strongly related especially for navigation terms. Since the Maanyan Dayaks
      live along the Barito river in Kalimantan (Borneo) and they do not possess the
      necessary skill for long maritime navigation, they were probably brought as
      subordinates by Malay sailors. In a recent paper we compared 23 different
      Malagasy dialects in order to determine the time and the landing area of the
      first colonization. In this research we use new data and new methods to confirm
      that the landing took place on the south-east coast of the Island. Furthermore,
      we are able to state here that colonization probably consisted of a single
      founding event rather than multiple settlements. To reach our goal we find out
      the internal kinship relations among all the 23 Malagasy dialects and we also
      find out the relations of the 23 dialects to Malay and Maanyan. The method used
      is an automated version of the lexicostatistic approach. The data from Madagascar
      were collected by the author at the beginning of 2010 and consist of Swadesh
      lists of 200 items for 23 dialects covering all areas of the Island. The lists
      for Maanyan and Malay were obtained from a published dataset integrated with the
      author's interviews.

PMID- 22363466
TI  - Lysine residue at position 22 of the AID protein regulates its class switch
      activity.
AB  - BACKGROUND: Activation induced deaminase (AID) mediates class switch
      recombination and somatic hypermutation of immunoglobulin (Ig) genes in germinal
      centre B cells. In order to regulate its specific activity and as a means to keep
      off-target mutations low, several mechanisms have evolved, including binding to
      specific cofactors, phosphorylation and destabilization of nuclear AID protein.
      Although ubiquitination at lysine residues of AID is recognized as an essential
      step in initiating degradation of nuclear AID, any functional relevance of lysine
      modifications has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      report functional implications of lysine modifications of the human AID protein
      by generating a panel of lysine to arginine mutants of AID and assessment of
      their catalytic class switch activity. We found that only mutation of Lys22 to
      Arg resulted in a significant reduction of class switching to IgG1 in transfected
      primary mouse B cells. This decrease in activity was neither reflected in reduced
      hypermutation of Ig genes in AID-mutant transfected DT40 B cell lines nor
      recapitulated in bacterial deamination assays, pointing to involvement of post
      translational modification of Lys22 for AID activity in B cells.
      CONCLUSIONS/SIGNIFICANCE: Our results imply that lysine modification may
      represent a novel level of AID regulation and that Lys22 is important for
      effective AID activity.

PMID- 22363467
TI  - HIV prevention in high-risk women in South Africa: condom use and the need for
      change.
AB  - INTRODUCTION: Young women are at disproportionate risk of HIV infection in South
      Africa. Understanding risk behaviors and factors associated with ability to
      negotiate safe sex and condom use is likely to be key in curbing the spread of
      HIV. Traditionally prevention efforts have focused on creating behavioral changes
      by increasing knowledge about HIV/AIDS. METHODS: This was a cross-sectional
      analysis from a prospective observational cohort study of 245 women at a high
      risk of HIV infection in KwaZulu-Natal, South Africa. RESULTS: Participants
      demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants
      reported condom use. Reported condom use at last sexual encounter varied slightly
      by partner type (57.0% with steady versus 64.4% with casual partners), and self
      perceived ability to choose to use a condom was significantly lower with steady
      partners compared to casual partners (p<0.01). In multivariate analysis, women
      who had high school education were more likely to use condoms at their last sex
      encounter compared to those with only primary school education (RR of 1.36 (95%
      Confidence Interval (CI) 1.06-1.75) and 1.46 (95% CI 1.13-1.88) for grades 8-10
      and 11-12, respectively). Those who used condoms as a contraceptive method were
      twice as likely to use condoms compared to women who did not report using them as
      a contraceptive method. Greater perceived ability to choose to use condoms was
      associated with higher self-reported condom use at last encounter, irrespective
      of partner type (RR = 2.65 (95% CI 2.15-32.5). DISCUSSION: Self-perceived ability
      to use condoms, level of formal education and condom use as a contraceptive were
      all significantly associated with self-reported condom use at last sexual
      encounter. These findings suggest that that gender inequality and access to
      formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual
      practices in South Africa.

PMID- 22363469
TI  - TIM-3 expression characterizes regulatory T cells in tumor tissues and is
      associated with lung cancer progression.
AB  - BACKGROUND: T cell immunoglobulin-3 (TIM-3) has been established as a negative
      regulatory molecule and plays a critical role in immune tolerance. TIM-3 is
      upregulated in exhausted CD8(+) T cells in both chronic infection and tumor.
      However, the nature of TIM-3(+)CD4(+) T cells in the tumor microenvironment is
      unclear. This study is to characterize TIM-3 expressing lymphocytes within human
      lung cancer tissues and establish clinical significance of TIM-3 expression in
      lung cancer progression. METHODOLOGY: A total of 51 human lung cancer tissue
      specimens were obtained from pathologically confirmed and newly diagnosed non
      small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal
      normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed
      for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor
      infiltrating lymphocytes (TILs) was correlated with clinicopathological
      parameters. CONCLUSIONS: TIM-3 is highly upregulated on both CD4(+) and CD8(+)
      TILs from human lung cancer tissues but negligibly expressed on T cells from
      patients' peripheral blood. Frequencies of IFN-gamma(+) cells were reduced in TIM
      3(+)CD8(+) TILs compared to TIM-3(-)CD8(+) TILs. However, the level of TIM-3
      expression on CD8(+) TILs failed to associate with any clinical pathological
      parameter. Interestingly, we found that approximately 70% of TIM-3(+)CD4(+) TILs
      expressed FOXP3 and about 60% of FOXP3(+) TILs were TIM-3(+). Importantly, TIM-3
      expression on CD4(+) T cells correlated with poor clinicopathological parameters
      of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a
      new role of TIM-3 as an important immune regulator in the tumor microenvironment
      via its predominant expression in regulatory T cells.

PMID- 22363468
TI  - Anandamide induces sperm release from oviductal epithelia through nitric oxide
      pathway in bovines.
AB  - Mammalian spermatozoa are not able to fertilize an egg immediately upon
      ejaculation. They acquire this ability during their transit through the female
      genital tract in a process known as capacitation. The mammalian oviduct acts as a
      functional sperm reservoir providing a suitable environment that allows the
      maintenance of sperm fertilization competence until ovulation occurs. After
      ovulation, spermatozoa are gradually released from the oviductal reservoir in the
      caudal isthmus and ascend to the site of fertilization. Capacitating-related
      changes in sperm plasma membrane seem to be responsible for sperm release from
      oviductal epithelium. Anandamide is a lipid mediator that participates in the
      regulation of several female and male reproductive functions. Previously we have
      demonstrated that anandamide was capable to release spermatozoa from oviductal
      epithelia by induction of sperm capacitation in bovines. In the present work we
      studied whether anandamide might exert its effect by activating the nitric oxide
      (NO) pathway since this molecule has been described as a capacitating agent in
      spermatozoa from different species. First, we demonstrated that 1 uM NOC-18, a NO
      donor, and 10 mM L-Arginine, NO synthase substrate, induced the release of
      spermatozoa from the oviductal epithelia. Then, we observed that the anandamide
      effect on sperm oviduct interaction was reversed by the addition of 1 uM L-NAME,
      a NO synthase inhibitor, or 30 ug/ml Hemoglobin, a NO scavenger. We also
      demonstrated that the induction of bull sperm capacitation by nanomolar
      concentrations of R(+)-methanandamide or anandamide was inhibited by adding L
      NAME or Hemoglobin. To study whether anandamide is able to produce NO, we
      measured this compound in both sperm and oviductal cells. We observed that
      anandamide increased the levels of NO in spermatozoa, but not in oviductal cells.
      These findings suggest that anandamide regulates the sperm release from oviductal
      epithelia probably by activating the NO pathway during sperm capacitation.

PMID- 22363470
TI  - Win-stay-lose-learn promotes cooperation in the spatial prisoner's dilemma game.
AB  - Holding on to one's strategy is natural and common if the later warrants success
      and satisfaction. This goes against widespread simulation practices of
      evolutionary games, where players frequently consider changing their strategy
      even though their payoffs may be marginally different than those of the other
      players. Inspired by this observation, we introduce an aspiration-based win-stay
      lose-learn strategy updating rule into the spatial prisoner's dilemma game. The
      rule is simple and intuitive, foreseeing strategy changes only by dissatisfied
      players, who then attempt to adopt the strategy of one of their nearest
      neighbors, while the strategies of satisfied players are not subject to change.
      We find that the proposed win-stay-lose-learn rule promotes the evolution of
      cooperation, and it does so very robustly and independently of the initial
      conditions. In fact, we show that even a minute initial fraction of cooperators
      may be sufficient to eventually secure a highly cooperative final state. In
      addition to extensive simulation results that support our conclusions, we also
      present results obtained by means of the pair approximation of the studied game.
      Our findings continue the success story of related win-stay strategy updating
      rules, and by doing so reveal new ways of resolving the prisoner's dilemma.

PMID- 22363471
TI  - Receptors for hyaluronic acid and poliovirus: a combinatorial role in glioma
      invasion?
AB  - BACKGROUND: CD44 has long been associated with glioma invasion while, more
      recently, CD155 has been implicated in playing a similar role. Notably, these two
      receptors have been shown closely positioned on monocytes. METHODS AND FINDINGS:
      In this study, an up-regulation of CD44 and CD155 was demonstrated in established
      and early-passage cultures of glioblastoma. Total internal reflected fluorescence
      (TIRF) microscopy revealed close proximity of CD44 and CD155. CD44 antibody
      blocking and gene silencing (via siRNA) resulted in greater inhibition of
      invasion than that for CD155. Combined interference resulted in 86% inhibition of
      invasion, although in these investigations no obvious evidence of synergy between
      CD44 and CD155 in curbing invasion was shown. Both siRNA-CD44 and siRNA-CD155
      treated cells lacked processes and were rounder, while live cell imaging showed
      reduced motility rate compared to wild type cells. Adhesion assay demonstrated
      that wild type cells adhered most efficiently to laminin, whereas siRNA-treated
      cells (p<0.0001 for both CD44 and CD155 expression) showed decreased adhesion on
      several ECMs investigated. BrdU assay showed a higher proliferation of siRNA-CD44
      and siRNA-CD155 cells, inversely correlated with reduced invasion. Confocal
      microscopy revealed overlapping of CD155 and integrins (beta(1), alpha(v)beta(1)
      and alpha(v)beta(3)) on glioblastoma cell processes whereas siRNA-transfected
      cells showed consequent reduction in integrin expression with no specific
      staining patterns. Reduced expression of Rho GTPases, Cdc42, Rac1/2/3, RhoA and
      RhoB, was seen in siRNA-CD44 and siRNA-CD155 cells. In contrast to CD44-knockdown
      and 'double'-knockdown cells, no obvious decrease in RhoC expression was observed
      in CD155-knockdown cells. CONCLUSIONS: This investigation has enhanced our
      understanding of cell invasion and confirmed CD44 to play a more significant role
      in this biological process than CD155. Joint CD44/CD155 approaches may, however,
      merit further study in therapeutic targeting of infiltrating glioma cells.

PMID- 22363472
TI  - The obesity and fatty liver are reduced by plant-derived Pediococcus pentosaceus
      LP28 in high fat diet-induced obese mice.
AB  - We evaluated the effect of an oral administration of a plant-derived lactic acid
      bacterium, Pediococcus pentosaceus LP28 (LP28), on metabolic syndrome by using
      high fat diet-induced obese mice. The obese mice were divided into 2 groups and
      fed either a high fat or regular diet for 8 weeks. Each group was further divided
      into 3 groups, which took LP28, another plant-derived Lactobacillus plantarum
      SN13T (SN13T) or no lactic acid bacteria (LAB). The lean control mice were fed a
      regular diet without inducing obesity prior to the experiment. LP28 reduced body
      weight gain and liver lipid contents (triglyceride and cholesterol), in mice fed
      a high fat diet for 8 weeks (40%, 54%, and 70% less than those of the control
      group without LAB, and P = 0.018, P<0.001, and P = 0.021, respectively), whereas
      SN13T and the heat treated LP28 at 121 degrees C for 15 min were ineffective.
      Abdominal visceral fat in the high fat diet mice fed with LP28 was also lower
      than that without LAB by 44%, although it was not significant but borderline (P =
      0.076). The sizes of the adipocytes and the lipid droplets in the livers were
      obviously decreased. A real-time PCR analyses showed that lipid metabolism
      related genes, such as CD36 (P = 0.013), SCD1 encoding stearoyl-CoA desaturase 1
      (not significant but borderline, P = 0.066), and PPARgamma encoding peroxisome
      proliferator-activated receptor gamma (P = 0.039), were down-regulated by taking
      LP28 continuously, when compared with those of the control group. In conclusion,
      LP28 may be a useful LAB strain for the prevention and reduction of the metabolic
      syndrome.

PMID- 22363473
TI  - Neuroprotection or increased brain damage mediated by temperature in stroke is
      time dependent.
AB  - The control of temperature during the acute phase of stroke may be a new
      therapeutic target that can be applied in all stroke patients, however
      therapeutic window or timecourse of the temperature effect is not well
      established. Our aim is to study the association between changes in body
      temperature in the first 72 hours and outcome in patients with ischemic (IS) and
      hemorrhagic (ICH) stroke. We prospectively studied 2931 consecutive patients
      (2468 with IS and 463 with ICH). Temperature was obtained at admission, and at
      24, 48 and 72 hours after admission. Temperature was categorized as low (<36
      degrees C), normal (36-37 degrees C) and high (>37 degrees C). As the main
      variable, we studied functional outcome at 3 months determined by modified Rankin
      Scale.Temperature in stroke patients is higher than in controls, and increases
      gradually in the first 72 hours after stroke. A positive correlation between
      temperature and stroke severity determined by NIHSS was found at 24 and 48 hours,
      but not at admission or 72 hours. In a logistic regression model, high
      temperature was associated with poor outcome at 24 hours (OR 2.05, 95% CI 1.59
      2.64, p<0.0001) and 48 hours (OR 1.93, 95% CI 1.08-2.34, p = 0.007), but not at
      admission or 72 hours.Temperature increases in patients with stroke in the first
      72 hours, with the harmful effect of high temperature occurring in the first 48
      hours. The neuroprotective effect of low temperature occurs within the first 24
      hours from stroke onset.

PMID- 22363474
TI  - Antagonistic roles of SEPALLATA3, FT and FLC genes as targets of the polycomb
      group gene CURLY LEAF.
AB  - In Arabidopsis, mutations in the Pc-G gene CURLY LEAF (CLF) give early flowering
      plants with curled leaves. This phenotype is caused by mis-expression of the
      floral homeotic gene AGAMOUS (AG) in leaves, so that ag mutations largely
      suppress the clf phenotype. Here, we identify three mutations that suppress clf
      despite maintaining high AG expression. We show that the suppressors correspond
      to mutations in FPA and FT, two genes promoting flowering, and in SEPALLATA3
      (SEP3) which encodes a co-factor for AG protein. The suppression of the clf
      phenotype is correlated with low SEP3 expression in all case and reveals that
      SEP3 has a role in promoting flowering in addition to its role in controlling
      floral organ identity. Genetic analysis of clf ft mutants indicates that CLF
      promotes flowering by reducing expression of FLC, a repressor of flowering. We
      conclude that SEP3 is the key target mediating the clf phenotype, and that the
      antagonistic effects of CLF target genes masks a role for CLF in promoting
      flowering.

PMID- 22363475
TI  - Expression of the Arabidopsis thaliana BBX32 gene in soybean increases grain
      yield.
AB  - Crop yield is a highly complex quantitative trait. Historically, successful
      breeding for improved grain yield has led to crop plants with improved source
      capacity, altered plant architecture, and increased resistance to abiotic and
      biotic stresses. To date, transgenic approaches towards improving crop grain
      yield have primarily focused on protecting plants from herbicide, insects, or
      disease. In contrast, we have focused on identifying genes that, when expressed
      in soybean, improve the intrinsic ability of the plant to yield more. Through the
      large scale screening of candidate genes in transgenic soybean, we identified an
      Arabidopsis thaliana B-box domain gene (AtBBX32) that significantly increases
      soybean grain yield year after year in multiple transgenic events in multi
      location field trials. In order to understand the underlying physiological
      changes that are associated with increased yield in transgenic soybean, we
      examined phenotypic differences in two AtBBX32-expressing lines and found
      increases in plant height and node, flower, pod, and seed number. We propose that
      these phenotypic changes are likely the result of changes in the timing of
      reproductive development in transgenic soybean that lead to the increased
      duration of the pod and seed development period. Consistent with the role of
      BBX32 in A. thaliana in regulating light signaling, we show that the constitutive
      expression of AtBBX32 in soybean alters the abundance of a subset of gene
      transcripts in the early morning hours. In particular, AtBBX32 alters transcript
      levels of the soybean clock genes GmTOC1 and LHY-CCA1-like2 (GmLCL2). We propose
      that through the expression of AtBBX32 and modulation of the abundance of
      circadian clock genes during the transition from dark to light, the timing of
      critical phases of reproductive development are altered. These findings
      demonstrate a specific role for AtBBX32 in modulating soybean development, and
      demonstrate the validity of expressing single genes in crops to deliver increased
      agricultural productivity.

PMID- 22363476
TI  - Prevalence, causes and socio-economic determinants of vision loss in Cape Town,
      South Africa.
AB  - PURPOSE: To estimate the prevalence and causes of blindness and visual impairment
      in Cape Town, South Africa and to explore socio-economic and demographic
      predictors of vision loss in this setting. METHODS: A cross sectional population
      based survey was conducted in Cape Town. Eighty-two clusters were selected using
      probability proportionate to size sampling. Within each cluster 35 or 40 people
      aged 50 years and above were selected using compact segment sampling. Visual
      acuity of participants was assessed and eyes with a visual acuity less than 6/18
      were examined by an ophthalmologist to determine the cause of vision loss.
      Demographic data (age, gender and education) were collected and a socio-economic
      status (SES) index was created using principal components analysis. RESULTS: Out
      of 3100 eligible people, 2750 (89%) were examined. The sample prevalence of
      bilateral blindness (presenting visual acuity <3/60) was 1.4% (95% CI 0.9-1.8).
      Posterior segment diseases accounted for 65% of blindness and cataract was
      responsible for 27%. The prevalence of vision loss was highest among people over
      80 years (odds ratio (OR) 6.9 95% CI 4.6-10.6), those in the poorest SES group
      (OR 3.9 95% CI 2.2-6.7) and people with no formal education (OR 5.4 95% CI 1.7
      16.6). Cataract surgical coverage was 68% in the poorest SES tertile (68%)
      compared to 93% in the medium and 100% in the highest tertile. CONCLUSIONS: The
      prevalence of blindness among people >=50 years in Cape Town was lower than
      expected and the contribution of posterior segment diseases higher than
      previously reported in South Africa and Sub Saharan Africa. There were clear
      socio-economic disparities in prevalence of vision loss and cataract surgical
      coverage in this setting which need to be addressed in blindness prevention
      programs.

PMID- 22363477
TI  - Study of local hydrodynamic environment in cell-substrate adhesion using side
      view MUPIV technology.
AB  - Tumor cell adhesion to the endothelium under shear flow conditions is a critical
      step that results in circulation-mediated tumor metastasis. This study presents
      experimental and computational techniques for studying the local hydrodynamic
      environment around adherent cells and how local shear conditions affect cell-cell
      interactions on the endothelium in tumor cell adhesion. To study the local
      hydrodynamic profile around heterotypic adherent cells, a side-view flow chamber
      assay coupled with micro particle imaging velocimetry (MUPIV) technique was
      developed, where interactions between leukocytes and tumor cells in the near
      endothelial wall region and the local shear flow environment were characterized.
      Computational fluid dynamics (CFD) simulations were also used to obtain
      quantitative flow properties around those adherent cells. Results showed that
      cell dimension and relative cell-cell positions had strong influence on local
      shear rates. The velocity profile above leukocytes and tumor cells displayed very
      different patterns. Larger cell deformations led to less disturbance to the flow.
      Local shear rates above smaller cells were observed to be more affected by
      relative positions between two cells.

PMID- 22363478
TI  - Ab initio calculation of the Zn isotope effect in phosphates, citrates, and
      malates and applications to plants and soil.
AB  - Stable Zn isotopes are fractionated in roots and leaves of plants. Analyses
      demonstrate that the heavy Zn isotopes are enriched in the root system of plants
      with respect to shoots and leaves as well as the host soil, but the fractionation
      mechanisms remain unclear. Here we show that the origin of this isotope
      fractionation is due to a chemical isotope effect upon complexation by Zn malates
      and citrates in the aerial parts and by phosphates in the roots. We calculated
      the Zn isotope effect in aqueous citrates, malates, and phosphates by ab initio
      methods. For pH<5, the Zn isotopic compositions of the various parts of the
      plants are expected to be similar to those of groundwater. In the neutral to
      alkaline region, the calculations correctly predict that (66)Zn is enriched over
      (64)Zn in roots, which concentrate phosphates, with respect to leaves, which
      concentrate malates and citrates, by about one permil. It is proposed that Zn
      isotope fractionation represents a useful tracer of Zn availability and mobility
      in soils.

PMID- 22363479
TI  - Stimulus dependency of object-evoked responses in human visual cortex: an inverse
      problem for category specificity.
AB  - Many studies have linked the processing of different object categories to
      specific event-related potentials (ERPs) such as the face-specific N170. Despite
      reports showing that object-related ERPs are influenced by visual stimulus
      features, there is consensus that these components primarily reflect categorical
      aspects of the stimuli. Here, we re-investigated this idea by systematically
      measuring the effects of visual feature manipulations on ERP responses elicited
      by both structure-from-motion (SFM)-defined and luminance-defined object stimuli.
      SFM objects elicited a novel component at 200-250 ms (N250) over parietal and
      posterior temporal sites. We found, however, that the N250 amplitude was
      unaffected by restructuring SFM stimuli into meaningless objects based on
      identical visual cues. This suggests that this N250 peak was not uniquely linked
      to categorical aspects of the objects, but is strongly determined by visual
      stimulus features. We provide strong support for this hypothesis by
      parametrically manipulating the depth range of both SFM- and luminance-defined
      object stimuli and showing that the N250 evoked by SFM stimuli as well as the
      well-known N170 to static faces were sensitive to this manipulation. Importantly,
      this effect could not be attributed to compromised object categorization in low
      depth stimuli, confirming a strong impact of visual stimulus features on object
      related ERP signals. As ERP components linked with visual categorical object
      perception are likely determined by multiple stimulus features, this creates an
      interesting inverse problem when deriving specific perceptual processes from
      variations in ERP components.

PMID- 22363480
TI  - Potential cost-effectiveness of universal access to modern contraceptives in
      Uganda.
AB  - BACKGROUND: Over two thirds of women who need contraception in Uganda lack access
      to modern effective methods. This study was conducted to estimate the potential
      cost-effectiveness of achieving universal access to modern contraceptives in
      Uganda by implementing a hypothetical new contraceptive program (NCP) from both
      societal and governmental (Ministry of Health (MoH)) perspectives.
      METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to compare the NCP
      to the status quo or current contraceptive program (CCP). The model followed a
      hypothetical cohort of 15-year old girls over a lifetime horizon. Data were
      obtained from the Uganda National Demographic and Health Survey and from
      published and unpublished sources. Costs, life expectancy, disability-adjusted
      life expectancy, pregnancies, fertility and incremental cost-effectiveness
      measured as cost per life-year (LY) gained, cost per disability-adjusted life
      year (DALY) averted, cost per pregnancy averted and cost per unit of fertility
      reduction were calculated. Univariate and probabilistic sensitivity analyses were
      performed to examine the robustness of results. Mean discounted life expectancy
      and disability-adjusted life expectancy (DALE) were higher under the NCP vs. CCP
      (28.74 vs. 28.65 years and 27.38 vs. 27.01 respectively). Mean pregnancies and
      live births per woman were lower under the NCP (9.51 vs. 7.90 and 6.92 vs. 5.79
      respectively). Mean lifetime societal costs per woman were lower for the NCP from
      the societal perspective ($1,949 vs. $1,987) and the MoH perspective ($636 vs.
      $685). In the incremental analysis, the NCP dominated the CCP, i.e. it was both
      less costly and more effective. The results were robust to univariate and
      probabilistic sensitivity analysis. CONCLUSION/SIGNIFICANCE: Universal access to
      modern contraceptives in Uganda appears to be highly cost-effective. Increasing
      contraceptive coverage should be considered among Uganda's public health
      priorities.

PMID- 22363481
TI  - S. pombe kinesins-8 promote both nucleation and catastrophe of microtubules.
AB  - The kinesins-8 were originally thought to be microtubule depolymerases, but are
      now emerging as more versatile catalysts of microtubule dynamics. We show here
      that S. pombe Klp5-436 and Klp6-440 are non-processive plus-end-directed motors
      whose in vitro velocities on S. pombe microtubules at 7 and 23 nm s(-1) are too
      slow to keep pace with the growing tips of dynamic interphase microtubules in
      living S. pombe. In vitro, Klp5 and 6 dimers exhibit a hitherto-undescribed
      combination of strong enhancement of microtubule nucleation with no effect on
      growth rate or catastrophe frequency. By contrast in vivo, both Klp5 and Klp6
      promote microtubule catastrophe at cell ends whilst Klp6 also increases the
      number of interphase microtubule arrays (IMAs). Our data support a model in which
      Klp5/6 bind tightly to free tubulin heterodimers, strongly promoting the
      nucleation of new microtubules, and then continue to land as a tubulin-motor
      complex on the tips of growing microtubules, with the motors then dissociating
      after a few seconds residence on the lattice. In vivo, we predict that only at
      cell ends, when growing microtubule tips become lodged and their growth slows
      down, will Klp5/6 motor activity succeed in tracking growing microtubule tips.
      This mechanism would allow Klp5/6 to detect the arrival of microtubule tips at
      cells ends and to amplify the intrinsic tendency for microtubules to
      catastrophise in compression at cell ends. Our evidence identifies Klp5 and 6 as
      spatial regulators of microtubule dynamics that enhance both microtubule
      nucleation at the cell centre and microtubule catastrophe at the cell ends.

PMID- 22363482
TI  - A comparative study of human TLR 7/8 stimulatory trimer compositions in influenza
      A viral genomes.
AB  - BACKGROUND: Variation in the genomes of single-stranded RNA viruses affects their
      infectivity and pathogenicity in two ways. First, viral genome sequence
      variations lead to changes in viral protein sequences and activities. Second,
      viral genome sequence variation produces diversity at the level of nucleotide
      composition and diversity in the interactions between viral RNAs and host toll
      like receptors (TLRs). A viral genome-typing method based on this type of
      diversity has not yet been established. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we propose a novel genomic trait called the "TLR stimulatory trimer
      composition" (TSTC) and two quantitative indicators, Score S and Score N, named
      "TLR stimulatory scores" (TSS). Using the complete genome sequences of 10,994
      influenza A viruses (IAV) and 251 influenza B viruses, we show that TSTC analysis
      reveals the diversity of Score S and Score N among the IAVs isolated from various
      hosts. In addition, we show that low values of Score S are correlated with high
      pathogenicity and pandemic potential in IAVs. Finally, we use Score S and Score N
      to construct a logistic regression model to recognize IAV strains that are highly
      pathogenic or have high pandemic potential. CONCLUSIONS/SIGNIFICANCE: Results
      from the TSTC analysis indicate that there are large differences between human
      and avian IAV genomes (except for segment 3), as illustrated by Score S.
      Moreover, segments 1, 2, 3 and 4 may be major determinants of the stimulatory
      activity exerted on human TLRs 7 and 8. We also find that a low Score S value is
      associated with high pathogenicity and pandemic potential in IAV. The pi value
      from the TSS-derived logistic regression model is useful for recognizing emerging
      IAVs that have high pathogenicity and pandemic potential.

PMID- 22363483
TI  - A heterogeneous in vitro three dimensional model of tumour-stroma interactions
      regulating sprouting angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels, is an essential process for
      tumour progression and is an area of significant therapeutic interest. Different
      in vitro systems and more complex in vivo systems have been described for the
      study of tumour angiogenesis. However, there are few human 3D in vitro systems
      described to date which mimic the cellular heterogeneity and complexity of
      angiogenesis within the tumour microenvironment. In this study we describe the
      Minitumour model--a 3 dimensional human spheroid-based system consisting of
      endothelial cells and fibroblasts in co-culture with the breast cancer cell line
      MDA-MB-231, for the study of tumour angiogenesis in vitro. After implantation in
      collagen-I gels, Minitumour spheroids form quantifiable endothelial capillary
      like structures. The endothelial cell pre-capillary sprouts are supported by the
      fibroblasts, which act as mural cells, and their growth is increased by the
      presence of cancer cells. Characterisation of the Minitumour model using small
      molecule inhibitors and inhibitory antibodies show that endothelial sprout
      formation is dependent on growth factors and cytokines known to be important for
      tumour angiogenesis. The model also shows a response to anti-angiogenic agents
      similar to previously described in vivo data. We demonstrate that independent
      manipulation of the different cell types is possible, using common molecular
      techniques, before incorporation into the model. This aspect of Minitumour
      spheroid analysis makes this model ideal for high content studies of gene
      function in individual cell types, allowing for the dissection of their roles in
      cell-cell interactions. Finally, using this technique, we were able to show the
      requirement of the metalloproteinase MT1-MMP in endothelial cells and
      fibroblasts, but not cancer cells, for sprouting angiogenesis.

PMID- 22363484
TI  - Large-scale cortical dynamics of sleep slow waves.
AB  - Slow waves constitute the main signature of sleep in the electroencephalogram
      (EEG). They reflect alternating periods of neuronal hyperpolarization and
      depolarization in cortical networks. While recent findings have demonstrated
      their functional role in shaping and strengthening neuronal networks, a large
      scale characterization of these two processes remains elusive in the human brain.
      In this study, by using simultaneous scalp EEG and intracranial recordings in 10
      epileptic subjects, we examined the dynamics of hyperpolarization and
      depolarization waves over a large extent of the human cortex. We report that both
      hyperpolarization and depolarization processes can occur with two different
      characteristic time durations which are consistent across all subjects. For both
      hyperpolarization and depolarization waves, their average speed over the cortex
      was estimated to be approximately 1 m/s. Finally, we characterized their
      propagation pathways by studying the preferential trajectories between most
      involved intracranial contacts. For both waves, although single events could
      begin in almost all investigated sites across the entire cortex, we found that
      the majority of the preferential starting locations were located in frontal
      regions of the brain while they had a tendency to end in posterior and temporal
      regions.

PMID- 22363485
TI  - Bone marrow osteoblast damage by chemotherapeutic agents.
AB  - Hematopoietic reconstitution, following bone marrow or stem cell transplantation,
      requires a microenvironment niche capable of supporting both immature progenitors
      and stem cells with the capacity to differentiate and expand. Osteoblasts
      comprise one important component of this niche. We determined that treatment of
      human primary osteoblasts (HOB) with melphalan or VP-16 resulted in increased
      phospho-Smad2, consistent with increased TGF-beta1 activity. This increase was
      coincident with reduced HOB capacity to support immature B lineage cell
      chemotaxis and adherence. The supportive deficit was not limited to committed
      progenitor cells, as human embryonic stem cells (hESC) or human CD34+ bone marrow
      cells co-cultured with HOB pre-exposed to melphalan, VP-16 or rTGF-beta1 had
      profiles distinct from the same populations co-cultured with untreated HOB.
      Functional support deficits were downstream of changes in HOB gene expression
      profiles following chemotherapy exposure. Melphalan and VP-16 induced damage of
      HOB suggests vulnerability of this critical niche to therapeutic agents
      frequently utilized in pre-transplant regimens and suggests that dose escalated
      chemotherapy may contribute to post-transplantation hematopoietic deficits by
      damaging structural components of this supportive niche.

PMID- 22363486
TI  - The spider effect: morphological and orienting classification of microglia in
      response to stimuli in vivo.
AB  - The different morphological stages of microglial activation have not yet been
      described in detail. We transected the olfactory bulb of rats and examined the
      activation of the microglial system histologically. Six stages of bidirectional
      microglial activation (A) and deactivation (R) were observed: from stage 1A to
      6A, the cell body size increased, the cell process number decreased, and the cell
      processes retracted and thickened, orienting toward the direction of the injury
      site; until stage 6A, when all processes disappeared. In contrast, in
      deactivation stages 6R to 1R, the microglia returned to the original site
      exhibiting a stepwise retransformation to the original morphology. Thin highly
      branched processes re-formed in stage 1R, similar to those in stage 1A. This
      reverse transformation mirrored the forward transformation except in stages 6R to
      1R: cells showed multiple nuclei which were slowly absorbed. Our findings support
      a morphologically defined stepwise activation and deactivation of microglia
      cells.

PMID- 22363487
TI  - Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the
      Notch signaling pathway in tubular epithelial cells.
AB  - BACKGROUND: Hypoxia-induced renal tubular cell epithelial-mesenchymal transition
      (EMT) is an important event leading to renal fibrosis. MicroRNAs (miRNAs) are
      small non-coding RNA molecules that bind to their mRNA targets, thereby leading
      to translational repression. The role of miRNA in hypoxia-induced EMT is largely
      unknown. METHODOLOGY/PRINCIPAL FINDINGS: miRNA profiling was performed for the
      identification of differentially expressed miRNAs in HK-2 cells under normal and
      low oxygen, and the results were then verified by quantitative real time RT-PCR
      (qRT-PCR). The function of miRNAs in hypoxia-induced renal tubular cell EMT was
      assessed by the transfection of specific miRNA inhibitors and mimics. Luciferase
      reporter gene assays and western blot analysis were performed to validate the
      target genes of miR-34a. siRNA against Jagged1 was designed to investigate the
      role of the miR-34a-Notch pathway in hypoxia induced renal tubular cell EMT.
      miRNA-34a was identified as being downregulated in hypoxic renal tubular
      epithelial cells. Inhibition of miR-34a expression in HK-2 cells, which highly
      express endogenous miR-34a, promoted a mesenchymal phenotype accompanied by
      reduced expression of the epithelial marker Z0-1, E-cadherin and increased
      expression of the mesenchymal markers alpha-SMA and vimentin. Conversely, miR-34a
      mimics effectively prevented hypoxia-induced EMT. Transfection of miRNA-34a in HK
      2 cells under hypoxia abolished hypoxia-induced expression of Notch1 and Jagged1
      as well as Notch downstream signals, such as snail. Western blot analysis and
      luciferase reporter gene assays showed direct evidence for miR-34a targeting
      Notch1 and Jagged1. siRNAs against Jagged1 or Notch1 effectively prevented miR
      34a inhibitor-induced tubular epithelial cell EMT. CONCLUSIONS/SIGNIFICANCE: Our
      study provides evidence that the hypoxia-induced decrease of miR-34a expression
      could promote EMT in renal tubular epithelial cells by directly targeting Notch1
      and Jagged1, and subsequently, Notch downstream signaling.

PMID- 22363489
TI  - The prevalence and risk factors for pneumococcal colonization of the nasopharynx
      among children in Kilifi District, Kenya.
AB  - BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage
      of vaccine-serotype pneumococci but increase in the carriage of non-vaccine
      serotypes. We studied the epidemiology of carriage among children 3-59 months old
      before vaccine introduction in Kilifi, Kenya. METHODS: In a rolling cross
      sectional study from October 2006 to December 2008 we approached 3570 healthy
      children selected at random from the population register of the Kilifi Health and
      Demographic Surveillance System and 134 HIV-infected children registered at a
      specialist clinic. A single nasopharyngeal swab was transported in STGG and
      cultured on gentamicin blood agar. A single colony of pneumococcus was serotyped
      by Quellung reaction. RESULTS: Families of 2840 children in the population-based
      sample and 99 in the HIV-infected sample consented to participate; carriage
      prevalence was 65.8% (95% CI, 64.0-67.5%) and 76% (95% CI, 66-84%) in the two
      samples, respectively. Carriage prevalence declined progressively with age from
      79% at 6-11 months to 51% at 54-59 months (p<0.0005). Carriage was positively
      associated with coryza (Odds ratio 2.63, 95%CI 2.12-3.25) and cough (1.55, 95%CI
      1.26-1.91) and negatively associated with recent antibiotic use (0.53 95%CI 0.34
      0.81). 53 different serotypes were identified and 42% of isolates were of
      serotypes contained in the 10-valent PCV. Common serotypes declined in prevalence
      with age while less common serotypes did not. CONCLUSION: Carriage prevalence in
      children was high, serotypes were diverse, and the majority of strains were of
      serotypes not represented in the 10-valent PCV. Vaccine introduction in Kenya
      will provide a natural test of virulence for the many circulating non-vaccine
      serotypes.

PMID- 22363488
TI  - Haplotype affinities resolve a major component of goat (Capra hircus) MtDNA D
      loop diversity and reveal specific features of the Sardinian stock.
AB  - Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the
      overall diversity and is found in locations as distant as Eastern Asia and
      Southern Africa. Its phylogenetic dissection would cast light on an important
      portion of the spread of goat breeding. The aims of this work were 1) to provide
      an operational definition of meaningful mtDNA units within haplogroup A, 2) to
      investigate the mechanisms underlying the maintenance of diversity by considering
      the modes of selection operated by breeders and 3) to identify the peculiarities
      of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of
      animals (1,591) which represents a non-trivial quota of the entire goat
      population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA
      diversity of Western Eurasia in the number of variable sites, their mutational
      pattern and allele frequency. By using bayesian analysis, a distance-based tree
      and a network analysis, we recognized demographically coherent groups of
      sequences identified by particular subsets of the variable positions. The results
      showed that this assignment system could be reproduced in other studies,
      capturing the greatest part of haplotype diversity.We identified haplotype groups
      overrepresented in Sardinian goats as a result of founder effects. We found that
      breeders maintain diversity of matrilines most likely through equalization of the
      reproductive potential. Moreover, the relevant amount of inter-farm mtDNA
      diversity found does not increase proportionally with distance. Our results
      illustrate the effects of breeding practices on the composition of maternal gene
      pool and identify mtDNA types that may be considered in projects aimed at
      retrieving the maternal component of the oldest breeds of Sardinia.

PMID- 22363490
TI  - Characterization of ceftazidime resistance mechanisms in clinical isolates of
      Burkholderia pseudomallei from Australia.
AB  - Burkholderia pseudomallei is a gram-negative bacterium that causes the serious
      human disease, melioidosis. There is no vaccine against melioidosis and it can be
      fatal if not treated with a specific antibiotic regimen, which typically includes
      the third-generation cephalosporin, ceftazidime (CAZ). There have been several
      resistance mechanisms described for B. pseudomallei, of which the best described
      are amino acid changes that alter substrate specificity in the highly conserved
      class A beta-lactamase, PenA. In the current study, we sequenced penA from
      isolates sequentially derived from two melioidosis patients with wild-type (1.5
      ug/mL) and, subsequently, resistant (16 or >=256 ug/mL) CAZ phenotypes. We
      identified two single-nucleotide polymorphisms (SNPs) that directly increased CAZ
      hydrolysis. One SNP caused an amino acid substitution (C69Y) near the active site
      of PenA, whereas a second novel SNP was found within the penA promoter region. In
      both instances, the CAZ resistance phenotype corresponded directly with the SNP
      genotype. Interestingly, these SNPs appeared after infection and under selection
      from CAZ chemotherapy. Through heterologous cloning and expression, and
      subsequent allelic exchange in the native bacterium, we confirmed the role of
      penA in generating both low-level and high-level CAZ resistance in these clinical
      isolates. Similar to previous studies, the amino acid substitution altered
      substrate specificity to other beta-lactams, suggesting a potential fitness cost
      associated with this mutation, a finding that could be exploited to improve
      therapeutic outcomes in patients harboring CAZ resistant B. pseudomallei. Our
      study is the first to functionally characterize CAZ resistance in clinical
      isolates of B. pseudomallei and to provide proven and clinically relevant
      signatures for monitoring the development of antibiotic resistance in this
      important pathogen.

PMID- 22363491
TI  - Tooth loss and cardiovascular disease mortality risk--results from the Scottish
      Health Survey.
AB  - BACKGROUND: Tooth loss is associated with increased cardiovascular disease (CVD)
      mortality risk. This association may however be due to residual confounding. We
      aimed to assess whether tooth loss is associated with specific CVD mortality
      endpoints in a national population sample adjusting for potential confounders.
      METHODS AND RESULTS: We used a prospective cohort design and data from the
      Scottish Health Survey. We combined data from surveys in 1995, 1998, 2003 and
      linked this to mortality records. Dental status was classified through self
      reports as natural teeth only, natural teeth and dentures, and no natural teeth
      (edentate). Cox proportional hazards models were used to estimate risk of CVD
      mortality by dental status adjusting for potential confounders. The sample
      consisted of 12871 participants. They were followed for 8.0 (SD: 3.3) years.
      During 103173 person-years, there were 1480 cases of all-cause mortality, 498 of
      CVD, and 515 of cancer. After adjusting for demographic, socio-economic,
      behavioural and health status, edentate subjects had significantly higher risk of
      all-cause (HR, 1.30; 95% CI, 1.12,1.50) and CVD mortality (HR, 1.49; 95% CI,
      1.16,1.92) compared to subjects with natural teeth only. Dental status was not
      significantly associated with cancer mortality in fully adjusted analysis.
      Further analysis for CVD mortality showed that in the fully adjusted model,
      edentate subjects had 2.97 (95% CI, 1.46, 6.05) times higher risk for stroke
      related mortality. CONCLUSIONS: In a national population sample of Scottish
      adults, being edentate was an independent predictor of total CVD mortality,
      although this was mainly driven by fatal stroke events.

PMID- 22363492
TI  - Prediction of psilocybin response in healthy volunteers.
AB  - Responses to hallucinogenic drugs, such as psilocybin, are believed to be
      critically dependent on the user's personality, current mood state, drug pre
      experiences, expectancies, and social and environmental variables. However,
      little is known about the order of importance of these variables and their effect
      sizes in comparison to drug dose. Hence, this study investigated the effects of
      24 predictor variables, including age, sex, education, personality traits, drug
      pre-experience, mental state before drug intake, experimental setting, and drug
      dose on the acute response to psilocybin. The analysis was based on the pooled
      data of 23 controlled experimental studies involving 409 psilocybin
      administrations to 261 healthy volunteers. Multiple linear mixed effects models
      were fitted for each of 15 response variables. Although drug dose was clearly the
      most important predictor for all measured response variables, several non
      pharmacological variables significantly contributed to the effects of psilocybin.
      Specifically, having a high score in the personality trait of Absorption, being
      in an emotionally excitable and active state immediately before drug intake, and
      having experienced few psychological problems in past weeks were most strongly
      associated with pleasant and mystical-type experiences, whereas high Emotional
      Excitability, low age, and an experimental setting involving positron emission
      tomography most strongly predicted unpleasant and/or anxious reactions to
      psilocybin. The results confirm that non-pharmacological variables play an
      important role in the effects of psilocybin.

PMID- 22363493
TI  - Characterization of spontaneous bone marrow recovery after sublethal total body
      irradiation: importance of the osteoblastic/adipocytic balance.
AB  - Many studies have already examined the hematopoietic recovery after irradiation
      but paid with very little attention to the bone marrow microenvironment.
      Nonetheless previous studies in a murine model of reversible radio-induced bone
      marrow aplasia have shown a significant increase in alkaline phosphatase activity
      (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not
      due to cell proliferation but could be attributed to modifications of the
      properties of mesenchymal stem cells (MSC). We thus undertook a study to assess
      the kinetics of the evolution of MSC correlated to their hematopoietic supportive
      capacities in mice treated with sub lethal total body irradiation. In our study,
      colony-forming units-fibroblasts (CFU-Fs) assay showed a significant MSC rate
      increase in irradiated bone marrows. CFU-Fs colonies still possessed
      differentiation capacities of MSC but colonies from mice sacrificed 3 days after
      irradiation displayed high rates of ALP activity and a transient increase in
      osteoblastic markers expression while ppargamma and neuropilin-1 decreased.
      Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to
      controls, irradiated CFU-Fs significantly increased the proliferation rate of
      hematopoietic precursors and accelerated the differentiation toward the
      granulocytic lineage. Our data provide the first evidence of the key role exerted
      by the balance between osteoblasts and adipocytes in spontaneous bone marrow
      regeneration. First, (pre)osteoblast differentiation from MSC stimulated
      hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in
      a second time (pre)osteoblasts progressively disappeared in favour of adipocytic
      cells which down regulated the proliferation and granulocytic differentiation and
      then contributed to a return to pre-irradiation conditions.

PMID- 22363494
TI  - Mannose-binding lectin 2 polymorphisms do not influence frequency or type of
      infection in adults with chemotherapy induced neutropaenia.
AB  - BACKGROUND: Mannose-binding Lectin protein (MBL) has been suggested to be
      relevant in the defence against infections in immunosuppressed individuals. In a
      Swedish adult cohort immunosuppressed from both the underlying disease and from
      iatrogenic treatments for their underlying disease we investigated the role of
      MBL in susceptibility to infection. METHODS: In this cross sectional, prospective
      study, blood samples obtained from 96 neutropaenic febrile episodes, representing
      82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2
      gene. Concurrent measurement of plasma MBL protein concentrations was also
      performed for observation of acute response during febrile episodes. FINDINGS: No
      association was observed between MBL2 genotype or plasma MBL concentrations, and
      the type or frequency of infection. Adding to the literature, we found no
      evidence that viral infections or co-infections with virus and bacteria would be
      predisposed by MBL deficiency. We further saw no correlation between MBL2
      genotype and the risk of fever. However, fever duration in febrile neutropaenic
      episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients
      with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared
      with 3 days amongst patients with wildtype MBL2 genotype. INTERPRETATION: We
      found no clear association between infection, or infection type to MBL2 genotypes
      or plasma MBL concentration, and add to the reports casting doubts on the benefit
      of recombinant MBL replacement therapy use during iatrogenic neutropaenia.

PMID- 22363495
TI  - Control of glycogen content in retina: allosteric regulation of glycogen
      synthase.
AB  - Retinal tissue is exceptional because it shows a high level of energy metabolism.
      Glycogen content represents the only energy reserve in retina, but its levels are
      limited. Therefore, elucidation of the mechanisms controlling glycogen content in
      retina will allow us to understand retina response under local energy demands
      that can occur under normal and pathological conditions. Thus, we studied retina
      glycogen levels under different experimental conditions and correlated them with
      glucose-6-phosphate (G-6-P) content and glycogen synthase (GS) activity. Glycogen
      and G-6-P content were studied in ex vivo retinas from normal, fasted,
      streptozotocin-treated, and insulin-induced hypoglycemic rats. Expression levels
      of GS and its phosphorylated form were also analyzed. Ex vivo retina from normal
      rats showed low G-6-P (14+/-2 pmol/mg protein) and glycogen levels (43+/-3 nmol
      glycosyl residues/mg protein), which were increased 6 and 3 times, respectively,
      in streptozotocin diabetic rats. While no changes in phosphorylated GS levels
      were observed in any condition tested, a positive correlation was found between G
      6-P levels with GS activity and glycogen content. The results indicated that in
      vivo, retina glycogen may act as an immediately accessible energy reserve and
      that its content was controlled primarily by G-6-P allosteric activation of GS.
      Therefore, under hypoglycemic situations retina energy supply is strongly
      compromised and could lead to the alterations observed in type 1 diabetes.

PMID- 22363496
TI  - Absence of membrane phosphatidylcholine does not affect virulence and stress
      tolerance phenotypes in the opportunistic pathogen Pseudomonas aeruginosa.
AB  - During growth in presence of choline, both laboratory and clinical Pseudomonas
      aeruginosa strains synthesize phosphatidylcholine (PC), and PC makes up ~4% of
      the total membrane phospholipid content. In all the strains tested, PC synthesis
      occurred only when choline is provided exogenously. Mutants defective in
      synthesis of PC were generated in the strain backgrounds PAO1 and PA14. Minimum
      inhibitory concentration studies testing sensitivity of PC-deficient strains
      towards various antibiotics and cationic antimicrobial peptides revealed no
      differences as compared to wild-type strains. Mutants incapable of synthesizing
      PC were also found to be unaffected in motility and biofilm formation on abiotic
      surfaces, colonization of biotic surfaces and virulence in a mouse infection
      model. A global phenotypic microarray was further used to identify conditions
      wherein membrane PC may play a role of in P. aeruginosa. No culture conditions
      were identified wherein wild-type and PC-deficient mutants showed phenotypic
      differences. Membrane PC may serve a highly specific role during P. aeruginosa
      interactions with its eukaryotic hosts based on all the clinical strains tested
      retaining the ability to synthesize it during availability of choline.

PMID- 22363497
TI  - MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the
      innate immune response and the microglial activation state.
AB  - Increasing evidence supports the involvement of microRNAs (miRNAs) in
      inflammatory and immune processes in prion neuropathogenesis. MiRNAs are small,
      non-coding RNA molecules which are emerging as key regulators of numerous
      cellular processes. We established miR-146a over-expression in prion-infected
      mouse brain tissues concurrent with the onset of prion deposition and appearance
      of activated microglia. Expression profiling of a variety of central nervous
      system derived cell-lines revealed that miR-146a is preferentially expressed in
      cells of microglial lineage. Prominent up-regulation of miR-146a was evident in
      the microglial cell lines BV-2 following TLR2 or TLR4 activation and also EOC
      13.31 via TLR2 that reached a maximum 24-48 hours post-stimulation, concomitant
      with the return to basal levels of transcription of induced cytokines. Gain- and
      loss-of-function studies with miR-146a revealed a substantial deregulation of
      inflammatory response pathways in response to TLR2 stimulation. Significant
      transcriptional alterations in response to miR-146a perturbation included
      downstream mediators of the pro-inflammatory transcription factor, nuclear factor
      kappa B (NF-kappaB) and the JAK-STAT signaling pathway. Microarray analysis also
      predicts a role for miR-146a regulation of morphological changes in microglial
      activation states as well as phagocytic mediators of the oxidative burst such as
      CYBA and NOS3. Based on our results, we propose a role for miR-146a as a potent
      modulator of microglial function by regulating the activation state during prion
      induced neurodegeneration.

PMID- 22363498
TI  - Synthetic Toll like receptor-4 (TLR-4) agonist peptides as a novel class of
      adjuvants.
AB  - BACKGROUND: Adjuvants serve as catalysts of the innate immune response by
      initiating a localized site of inflammation that is mitigated by the interactions
      between antigens and toll like receptor (TLR) proteins. Currently, the majority
      of vaccines are formulated with aluminum based adjuvants, which are associated
      with various side effects. In an effort to develop a new class of adjuvants,
      agonists of TLR proteins, such as bacterial products, would be natural
      candidates. Lipopolysaccharide (LPS), a major structural component of gram
      negative bacteria cell walls, induces the systemic inflammation observed in
      septic shock by interacting with TLR-4. The use of synthetic peptides of LPS or
      TLR-4 agonists, which mimic the interaction between TLR-4 and LPS, can
      potentially regulate cellular signal transduction pathways such that a localized
      inflammatory response is achieved similar to that generated by adjuvants.
      METHODOLOGY/PRINCIPAL FINDINGS: We report the identification and activity of
      several peptides isolated using phage display combinatorial peptide technology,
      which functionally mimicked LPS. The activity of the LPS-TLR-4 interaction was
      assessed by NF-kappaB nuclear translocation analyses in HEK-BLUETM-4 cells, a
      cell culture model that expresses only TLR-4, and the murine macrophage cell
      line, RAW264.7. Furthermore, the LPS peptide mimics were capable of inducing
      inflammatory cytokine secretion from RAW264.7 cells. Lastly, ELISA analysis of
      serum from vaccinated BALB/c mice revealed that the LPS peptide mimics act as a
      functional adjuvant. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the
      identification of synthetic peptides that mimic LPS by interacting with TLR-4.
      This LPS mimotope-TLR-4 interaction will allow for the development and use of
      these peptides as a new class of adjuvants, namely TLR-4 agonists.

PMID- 22363499
TI  - Role of mesenchymal stem cells on cornea wound healing induced by acute alkali
      burn.
AB  - The aim of this study was to investigate the effects of subconjunctivally
      administered mesenchymal stem cells (MSCs) on corneal wound healing in the acute
      stage of an alkali burn. A corneal alkali burn model was generated by placing a
      piece of 3-mm diameter filter paper soaked in NaOH on the right eye of 48 Sprague
      Dawley female rats. 24 rats were administered a subconjunctival injection of a
      suspension of 2*10(6) MSCs in 0.1 ml phosphate-buffered saline (PBS) on day 0 and
      day 3 after the corneal alkali burn. The other 24 rats were administered a
      subconjunctival injection of an equal amount of PBS as a control. Deficiencies of
      the corneal epithelium and the area of corneal neovascularization (CNV) were
      evaluated on days 3 and 7 after the corneal alkali burn. Infiltrated CD68(+)
      cells were detected by immunofluorescence staining. The mRNA expression levels of
      macrophage inflammatory protein-1 alpha (MIP-1alpha), tumor necrosis factor-alpha
      (TNF-alpha), monocyte chemotactic protein-1 (MCP-1) and vascular endothelial
      growth factor (VEGF) were analyzed using real-time polymerase chain reaction
      (real-time PCR). In addition, VEGF protein levels were analyzed using an enzyme
      linked immunosorbent assay (ELISA). MSCs significantly enhanced the recovery of
      the corneal epithelium and decreased the CNV area compared with the control
      group. On day 7, the quantity of infiltrated CD68(+) cells was significantly
      lower in the MSC group and the mRNA levels of MIP-1alpha, TNF-alpha, and VEGF and
      the protein levels of VEGF were also down-regulated. However, the expression of
      MCP-1 was not different between the two groups. Our results suggest that
      subconjunctival injection of MSCs significantly accelerates corneal wound
      healing, attenuates inflammation and reduces CNV in alkaline-burned corneas;
      these effects were found to be related to a reduction of infiltrated CD68(+)
      cells and the down-regulation of MIP-1alpha, TNF-alpha and VEGF.

PMID- 22363500
TI  - Effect of bilingualism on lexical stress pattern discrimination in French
      learning infants.
AB  - Monolingual infants start learning the prosodic properties of their native
      language around 6 to 9 months of age, a fact marked by the development of
      preferences for predominant prosodic patterns and a decrease in sensitivity to
      non-native prosodic properties. The present study evaluates the effects of
      bilingual acquisition on speech perception by exploring how stress pattern
      perception may differ in French-learning 10-month-olds raised in bilingual as
      opposed to monolingual environments. Experiment 1 shows that monolinguals can
      discriminate stress patterns following a long familiarization to one of two
      patterns, but not after a short familiarization. In Experiment 2, two subgroups
      of bilingual infants growing up learning both French and another language
      (varying across infants) in which stress is used lexically were tested under the
      more difficult short familiarization condition: one with balanced input, and one
      receiving more input in the language other than French. Discrimination was
      clearly found for the other-language-dominant subgroup, establishing heightened
      sensitivity to stress pattern contrasts in these bilinguals as compared to
      monolinguals. However, the balanced bilinguals' performance was not better than
      that of monolinguals, establishing an effect of the relative balance of the
      language input. This pattern of results is compatible with the proposal that
      sensitivity to prosodic contrasts is maintained or enhanced in a bilingual
      population compared to a monolingual population in which these contrasts are non
      native, provided that this dimension is used in one of the two languages in
      acquisition, and that infants receive enough input from that language.

PMID- 22363501
TI  - Subcellular localization of class II HDAs in Arabidopsis thaliana:
      nucleocytoplasmic shuttling of HDA15 is driven by light.
AB  - Class II histone deacetylases in humans and other model organisms undergo
      nucleocytoplasmic shuttling. This unique functional regulatory mechanism has been
      well elucidated in eukaryotic organisms except in plant systems. In this study,
      we have paved the baseline evidence for the cytoplasmic and nuclear localization
      of Class II HDAs as well as their mRNA expression patterns. RT-PCR analysis on
      the different vegetative parts and developmental stages reveal that Class II HDAs
      are ubiquitously expressed in all tissues with minimal developmental specificity.
      Moreover, stable and transient expression assays using HDA-YFP/GFP fusion
      constructs indicate cytoplasmic localization of HDA5, HDA8, and HDA14 further
      suggesting their potential for nuclear transport and deacetylating organellar and
      cytoplasmic proteins. Organelle markers and stains confirm HDA14 to abound in the
      mitochondria and chloroplasts while HDA5 localizes in the ER. HDA15, on the other
      hand, shuttles in and out of the nucleus upon light exposure. In the absence of
      light, it is exported out of the nucleus where further re-exposition to light
      treatments signals its nuclear import. Unlike HDA5 which binds with 14-3-3
      proteins, HDA15 fails to interact with these chaperones. Instead, HDA15 relies on
      its own nuclear localization and export signals to navigate its subcellular
      compartmentalization classifying it as a Class IIb HDA. Our study indicates that
      nucleocytoplasmic shuttling is indeed a hallmark for all eukaryotic Class II
      histone deacetylases.

PMID- 22363502
TI  - Retinoic acid signaling plays a restrictive role in zebrafish primitive
      myelopoiesis.
AB  - Retinoic acid (RA) is known to regulate definitive myelopoiesis but its role in
      vertebrate primitive myelopoiesis remains unclear. Here we report that zebrafish
      primitive myelopoiesis is restricted by RA in a dose dependent manner mainly
      before 11 hpf (hours post fertilization) when anterior hemangioblasts are
      initiated to form. RA treatment significantly reduces expressions of anterior
      hemangioblast markers scl, lmo2, gata2 and etsrp in the rostral end of ALPM
      (anterior lateral plate mesoderm) of the embryos. The result indicates that RA
      restricts primitive myelopoiesis by suppressing formation of anterior
      hemangioblasts. Analyses of ALPM formation suggest that the defective primitive
      myelopoiesis resulting from RA treatment before late gastrulation may be
      secondary to global loss of cells for ALPM fate whereas the developmental defect
      resulting from RA treatment during 10-11 hpf should be due to ALPM patterning
      shift. Overexpressions of scl and lmo2 partially rescue the block of primitive
      myelopoiesis in the embryos treated with 250 nM RA during 10-11 hpf, suggesting
      RA acts upstream of scl to control primitive myelopoiesis. However, the RA
      treatment blocks the increased primitive myelopoiesis caused by overexpressing
      gata4/6 whereas the abolished primitive myelopoiesis in gata4/5/6 depleted
      embryos is well rescued by 4-diethylamino-benzaldehyde, a retinal dehydrogenase
      inhibitor, or partially rescued by knocking down aldh1a2, the major retinal
      dehydrogenase gene that is responsible for RA synthesis during early development.
      Consistently, overexpressing gata4/6 inhibits aldh1a2 expression whereas
      depleting gata4/5/6 increases aldh1a2 expression. The results reveal that RA
      signaling acts downstream of gata4/5/6 to control primitive myelopoiesis. But, 4
      diethylamino-benzaldehyde fails to rescue the defective primitive myelopoiesis in
      either cloche embryos or lycat morphants. Taken together, our results demonstrate
      that RA signaling restricts zebrafish primitive myelopoiesis through acting
      downstream of gata4/5/6, upstream of, or parallel to, cloche, and upstream of
      scl.

PMID- 22363503
TI  - iNR-PhysChem: a sequence-based predictor for identifying nuclear receptors and
      their subfamilies via physical-chemical property matrix.
AB  - Nuclear receptors (NRs) form a family of ligand-activated transcription factors
      that regulate a wide variety of biological processes, such as homeostasis,
      reproduction, development, and metabolism. Human genome contains 48 genes
      encoding NRs. These receptors have become one of the most important targets for
      therapeutic drug development. According to their different action mechanisms or
      functions, NRs have been classified into seven subfamilies. With the avalanche of
      protein sequences generated in the postgenomic age, we are facing the following
      challenging problems. Given an uncharacterized protein sequence, how can we
      identify whether it is a nuclear receptor? If it is, what subfamily it belongs
      to? To address these problems, we developed a predictor called iNR-PhysChem in
      which the protein samples were expressed by a novel mode of pseudo amino acid
      composition (PseAAC) whose components were derived from a physical-chemical
      matrix via a series of auto-covariance and cross-covariance transformations. It
      was observed that the overall success rate achieved by iNR-PhysChem was over 98%
      in identifying NRs or non-NRs, and over 92% in identifying NRs among the
      following seven subfamilies: NR1--thyroid hormone like, NR2--HNF4-like, NR3-
      estrogen like, NR4--nerve growth factor IB-like, NR5--fushi tarazu-F1 like, NR6-
      germ cell nuclear factor like, and NR0--knirps like. These rates were derived by
      the jackknife tests on a stringent benchmark dataset in which none of protein
      sequences included has >=60% pairwise sequence identity to any other in a same
      subset. As a user-friendly web-server, iNR-PhysChem is freely accessible to the
      public at either http://www.jci-bioinfo.cn/iNR-PhysChem or
      http://icpr.jci.edu.cn/bioinfo/iNR-PhysChem. Also a step-by-step guide is
      provided on how to use the web-server to get the desired results without the need
      to follow the complicated mathematics involved in developing the predictor. It is
      anticipated that iNR-PhysChem may become a useful high throughput tool for both
      basic research and drug design.

PMID- 22363504
TI  - Cystinosin, MPDU1, SWEETs and KDELR belong to a well-defined protein family with
      putative function of cargo receptors involved in vesicle trafficking.
AB  - Classification of proteins into families based on remote homology often helps
      prediction of their biological function. Here we describe prediction of protein
      cargo receptors involved in vesicle formation and protein trafficking. Hidden
      Markov model profile-to-profile searches in protein databases using endoplasmic
      reticulum lumen protein retaining receptors (KDEL, Erd2) as query reveal a large
      and diverse family of proteins with seven transmembrane helices and common
      topology and, most likely, similar function. Their coding genes exist in all
      eukaryota and in several prokaryota. Some are responsible for metabolic diseases
      (cystinosis, congenital disorder of glycosylation), others are candidate genes
      for genetic disorders (cleft lip and palate, certain forms of cancer) or solute
      uptake and efflux (SWEETs) and many have not yet been assigned a function.
      Comparison with the properties of KDEL receptors suggests that the family members
      could be involved in protein trafficking and serve as cargo receptors. This
      prediction sheds new light on a range of biologically, medically and
      agronomically important proteins and could open the way to discovering the
      function of many genes not yet annotated. Experimental testing is suggested.

PMID- 22363506
TI  - Novel covalently linked insulin dimer engineered to investigate the function of
      insulin dimerization.
AB  - An ingenious system evolved to facilitate insulin binding to the insulin receptor
      as a monomer and at the same time ensure sufficient stability of insulin during
      storage. Insulin dimer is the cornerstone of this system. Insulin dimer is
      relatively weak, which ensures dissociation into monomers in the circulation, and
      it is stabilized by hexamer formation in the presence of zinc ions during storage
      in the pancreatic beta-cell. Due to the transient nature of insulin dimer, direct
      investigation of this important form is inherently difficult. To address the
      relationship between insulin oligomerization and insulin stability and function,
      we engineered a covalently linked insulin dimer in which two monomers were linked
      by a disulfide bond. The structure of this covalent dimer was identical to the
      self-association dimer of human insulin. Importantly, this covalent dimer was
      capable of further oligomerization to form the structural equivalent of the
      classical hexamer. The covalently linked dimer neither bound to the insulin
      receptor, nor induced a metabolic response in vitro. However, it was extremely
      thermodynamically stable and did not form amyloid fibrils when subjected to
      mechanical stress, underlining the importance of oligomerization for insulin
      stability.

PMID- 22363505
TI  - A plasma biomarker signature of immune activation in HIV patients on
      antiretroviral therapy.
AB  - BACKGROUND: Immune activation is a strong predictor of disease progression in HIV
      infection. Combinatorial plasma biomarker signatures that represent surrogate
      markers of immune activation in both viremic and aviremic HIV patients on
      combination antiretroviral therapy (cART) have not been defined. Here, we
      identify a plasma inflammatory biomarker signature that distinguishes between
      both viremic and aviremic HIV patients on cART and healthy controls and examine
      relationships of this signature to markers of disease progression. METHODS:
      Multiplex profiling and ELISA were used to detect 15 cytokines/chemokines,
      soluble IL-2R (sIL-2R), and soluble CD14 (sCD14) in plasma from 57 HIV patients
      with CD4 nadir <300 cells/ul and 29 healthy controls. Supervised and unsupervised
      analyses were used to identify biomarkers explaining variance between groups
      defined by HIV status or drug abuse. Relationships between biomarkers and disease
      markers were examined by Spearman correlation. RESULTS: The majority (91%) of HIV
      subjects were on cART, with 38% having undetectable viral loads (VL).
      Hierarchical clustering identified a biomarker cluster in plasma consisting of
      two interferon-stimulated gene products (CXCL9 and CXCL10), T cell activation
      marker (sIL-2R), and monocyte activation marker (sCD14) that distinguished both
      viremic and aviremic HIV patients on cART from controls (p<0.0001) and were top
      ranked in variables important in projection plots. IL-12 and CCL4 were also
      elevated in viremic and aviremic patients compared to controls (p<0.05). IL-12
      correlated with IFNalpha, IFNgamma, CXCL9, and sIL-2R (p<0.05). CXCL10 correlated
      positively with plasma VL and percentage of CD16+ monocytes, and inversely with
      CD4 count (p = 0.001, <0.0001, and 0.04, respectively). CONCLUSION: A plasma
      inflammatory biomarker signature consisting of CXCL9, CXCL10, sIL-2R, and sCD14
      may be useful as a surrogate marker to monitor immune activation in both viremic
      and aviremic HIV patients on cART during disease progression and therapeutic
      responses.

PMID- 22363507
TI  - Infants in control: rapid anticipation of action outcomes in a gaze-contingent
      paradigm.
AB  - Infants' poor motor abilities limit their interaction with their environment and
      render studying infant cognition notoriously difficult. Exceptions are eye
      movements, which reach high accuracy early, but generally do not allow
      manipulation of the physical environment. In this study, real-time eye tracking
      is used to put 6- and 8-month-old infants in direct control of their visual
      surroundings to study the fundamental problem of discovery of agency, i.e. the
      ability to infer that certain sensory events are caused by one's own actions. We
      demonstrate that infants quickly learn to perform eye movements to trigger the
      appearance of new stimuli and that they anticipate the consequences of their
      actions in as few as 3 trials. Our findings show that infants can rapidly
      discover new ways of controlling their environment. We suggest that gaze
      contingent paradigms offer effective new ways for studying many aspects of infant
      learning and cognition in an interactive fashion and provide new opportunities
      for behavioral training and treatment in infants.

PMID- 22363508
TI  - Predicting landscape-genetic consequences of habitat loss, fragmentation and
      mobility for multiple species of woodland birds.
AB  - Inference concerning the impact of habitat fragmentation on dispersal and gene
      flow is a key theme in landscape genetics. Recently, the ability of established
      approaches to identify reliably the differential effects of landscape structure
      (e.g. land-cover composition, remnant vegetation configuration and extent) on the
      mobility of organisms has been questioned. More explicit methods of predicting
      and testing for such effects must move beyond post hoc explanations for single
      landscapes and species. Here, we document a process for making a priori
      predictions, using existing spatial and ecological data and expert opinion, of
      the effects of landscape structure on genetic structure of multiple species
      across replicated landscape blocks. We compare the results of two common methods
      for estimating the influence of landscape structure on effective distance: least
      cost path analysis and isolation-by-resistance. We present a series of
      alternative models of genetic connectivity in the study area, represented by
      different landscape resistance surfaces for calculating effective distance, and
      identify appropriate null models. The process is applied to ten species of
      sympatric woodland-dependant birds. For each species, we rank a priori the
      expectation of fit of genetic response to the models according to the expected
      response of birds to loss of structural connectivity and landscape-scale tree
      cover. These rankings (our hypotheses) are presented for testing with empirical
      genetic data in a subsequent contribution. We propose that this replicated
      landscape, multi-species approach offers a robust method for identifying the
      likely effects of landscape fragmentation on dispersal.

PMID- 22363510
TI  - RAMTaB: robust alignment of multi-tag bioimages.
AB  - BACKGROUND: In recent years, new microscopic imaging techniques have evolved to
      allow us to visualize several different proteins (or other biomolecules) in a
      visual field. Analysis of protein co-localization becomes viable because
      molecules can interact only when they are located close to each other. We present
      a novel approach to align images in a multi-tag fluorescence image stack. The
      proposed approach is applicable to multi-tag bioimaging systems which (a) acquire
      fluorescence images by sequential staining and (b) simultaneously capture a phase
      contrast image corresponding to each of the fluorescence images. To the best of
      our knowledge, there is no existing method in the literature, which addresses
      simultaneous registration of multi-tag bioimages and selection of the reference
      image in order to maximize the overall overlap between the images.
      METHODOLOGY/PRINCIPAL FINDINGS: We employ a block-based method for registration,
      which yields a confidence measure to indicate the accuracy of our registration
      results. We derive a shift metric in order to select the Reference Image with
      Maximal Overlap (RIMO), in turn minimizing the total amount of non-overlapping
      signal for a given number of tags. Experimental results show that the Robust
      Alignment of Multi-Tag Bioimages (RAMTaB) framework is robust to variations in
      contrast and illumination, yields sub-pixel accuracy, and successfully selects
      the reference image resulting in maximum overlap. The registration results are
      also shown to significantly improve any follow-up protein co-localization
      studies. CONCLUSIONS: For the discovery of protein complexes and of functional
      protein networks within a cell, alignment of the tag images in a multi-tag
      fluorescence image stack is a key pre-processing step. The proposed framework is
      shown to produce accurate alignment results on both real and synthetic data. Our
      future work will use the aligned multi-channel fluorescence image data for normal
      and diseased tissue specimens to analyze molecular co-expression patterns and
      functional protein networks.

PMID- 22363509
TI  - Multiple sources of contamination in samples from patients reported to have XMRV
      infection.
AB  - Xenotropic murine leukemia virus (MLV)-related retrovirus (XMRV) was reported to
      be associated with prostate cancer by Urisman, et al. in 2006 and chronic fatigue
      syndrome (CFS) by Lombardi, et al. in 2009. To investigate this association, we
      independently evaluated plasma samples from 4 patients with CFS reported by
      Lombardi, et al. to have XMRV infection and from 5 healthy controls reported to
      be XMRV uninfected. We also analyzed viral sequences obtained from supernatants
      of cell cultures found to contain XMRV after coculture with 9 clinical samples
      from 8 patients. A qPCR assay capable of distinguishing XMRV from endogenous MLVs
      showed that the viral sequences detected in the CFS patient plasma behaved like
      endogenous MLVs and not XMRV. Single-genome sequences (N = 89) from CFS patient
      plasma were indistinguishable from endogenous MLVs found in the mouse genome that
      are distinct from XMRV. By contrast, XMRV sequences were detected by qPCR in 2 of
      the 5 plasma samples from healthy controls (sequencing of the qPCR product
      confirmed XMRV not MLV). Single-genome sequences (N = 234) from the 9 culture
      supernatants reportedly positive for XMRV were indistinguishable from XMRV
      sequences obtained from 22Rv1 and XMRV-contaminated 293T cell-lines. These
      results indicate that MLV DNA detected in the plasma samples from CFS patients
      evaluated in this study was from contaminating mouse genomic DNA and that XMRV
      detected in plasma samples from healthy controls and in cultures of patient
      samples was due to cross-contamination with XMRV (virus or nucleic acid).

PMID- 22363511
TI  - The impact of different types of assistive devices on gait measures and safety in
      Huntington's disease.
AB  - BACKGROUND: Gait and balance impairments lead to frequent falls and injuries in
      individuals with Huntington's disease (HD). Assistive devices (ADs) such as canes
      and walkers are often prescribed to prevent falls, but their efficacy is unknown.
      We systematically examined the effects of different types of ADs on quantitative
      gait measures during walking in a straight path and around obstacles. METHODS:
      Spatial and temporal gait parameters were measured in 21 subjects with HD as they
      walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6
      commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3
      or 4 wheeled walker). Subjects also were timed and observed for number of
      stumbles and falls while walking around two obstacles in a figure-of-eight
      pattern. RESULTS: Gait measure variability (i.e., coefficient of variation), an
      indicator of fall risk, was consistently better when using the 4WW compared to
      other ADs. Subjects also walked the fastest and had the fewest number of stumbles
      and falls when using the 4WW in the figure-of-eight course. Subjects walked
      significantly slower using ADs compared to no AD both across the GAITRite and in
      the figure-of-eight. Measures reflecting gait stability and safety improved with
      the 4WW but were made worse by some other ADs.

PMID- 22363512
TI  - Intermittent hypoxia regulates stem-like characteristics and differentiation of
      neuroblastoma cells.
AB  - BACKGROUND: Neuroblastomas are the most common extracranial solid tumors in
      children. Neuroblastomas are derived from immature cells of the sympathetic
      nervous system and are characterized by clinical and biological heterogeneity.
      Hypoxia has been linked to tumor progression and increased malignancy.
      Intermittent hypoxia or repeated episodes of hypoxia followed by re-oxygenation
      is a common phenomenon in solid tumors including neuroblastoma and it has a
      significant influence on the outcome of therapies. The present study focuses on
      how intermittent hypoxia modulates the stem-like properties and differentiation
      in neuroblastoma cells. METHODS AND FINDINGS: Cell survival was assessed by
      clonogenic assay and cell differentiation was determined by morphological
      characterization. Hypoxia-inducible genes were analyzed by real-time PCR and
      Western blotting. Immunofluorescence, real-time PCR and Western blotting were
      utilized to study stem cell markers. Analysis of neural crest/sympathetic nervous
      system (SNS) markers and neuronal differentiation markers were done by real-time
      PCR and Western blotting, respectively. Intermittent hypoxia stimulated the
      levels of HIF-1alpha and HIF-2 alpha proteins and enhanced stem-like properties
      of neuroblastoma cells. In intermittent hypoxia-conditioned cells, downregulation
      of SNS marker genes and upregulation of genes expressed in the neural crest were
      observed. Intermittent hypoxia suppressed the retinoic acid-induced
      differentiation of neuroblastoma cells. CONCLUSIONS: Our results suggest that
      intermittent hypoxia enhances stem-like characteristics and suppresses
      differentiation propensities in neuroblastoma cells.

PMID- 22363513
TI  - Efficient exact maximum a posteriori computation for bayesian SNP genotyping in
      polyploids.
AB  - The problem of genotyping polyploids is extremely important for the creation of
      genetic maps and assembly of complex plant genomes. Despite its significance,
      polyploid genotyping still remains largely unsolved and suffers from a lack of
      statistical formality. In this paper a graphical bayesian model for SNP
      genotyping data is introduced. This model can infer genotypes even when the
      ploidy of the population is unknown. We also introduce an algorithm for finding
      the exact maximum a posteriori genotype configuration with this model. This
      algorithm is implemented in a freely available web-based software package
      SuperMASSA. We demonstrate the utility, efficiency, and flexibility of the model
      and algorithm by applying them to two different platforms, each of which is
      applied to a polyploid data set: Illumina GoldenGate data from potato and
      Sequenom MassARRAY data from sugarcane. Our method achieves state-of-the-art
      performance on both data sets and can be trivially adapted to use models that
      utilize prior information about any platform or species.

PMID- 22363514
TI  - Differences in MEF2 and NFAT transcriptional pathways according to human heart
      failure aetiology.
AB  - BACKGROUND: Ca(2+) handling machinery modulates the activation of cardiac
      transcription pathways involved in heart failure (HF). The present study
      investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1,
      MEF2C and GATA4 (transcription factors) in the same cardiac tissue. METHODOLOGY
      AND PRINCIPAL FINDINGS: A total of 83 hearts from ischemic (ICM, n = 43) and
      dilated (DCM, n = 31) patients undergoing heart transplantation and controls
      (CNT, n = 9) were analyzed by western blotting. Subcellular distribution was
      analyzed by fluorescence and electron microscopy. When we compared Ca(+2)
      handling proteins according to HF aetiology, ICM showed higher levels of
      calmodulin (24%, p<0.01), calcineurin (26%, p<0.01) and Ca(2+)/Calmodulin
      dependent kinase II (CaMKIIdelta(b) nuclear isoform 62%, p<0.001) than the CNT
      group. However, these proteins in DCM did not significantly increase.
      Furthermore, ICM showed a significant elevation in MEF2C (33%, p<0.01), and GATA4
      (49%, p<0.05); also NFAT1 (66%, p<0.001) was increased, producing the resultant
      translocation of this transcriptional factor into the nuclei. These results were
      supported by fluorescence and electron microscopy analysis. Whereas, DCM only had
      a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and
      MEF2C in both groups (ICM r = 0.38 and DCM r = 0.59, p<0.05 and p<0.01,
      respectively) were found; only ICM showed a correlation between GATA4 and NFAT1
      (r = 0.37, p<0.05). CONCLUSIONS/SIGNIFICANCE: This study shows an increase of
      Ca(2+) handling machinery synthesis and their cardiac transcription pathways in
      HF, being more markedly increased in ICM. Furthermore, there is a significant
      association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic
      targets to improve myocardial function.

PMID- 22363515
TI  - In vivo evidence that TRAF4 is required for central nervous system myelin
      homeostasis.
AB  - Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal
      transducers for the TNF and interleukin-1/Toll-like receptor superfamilies.
      However, TRAF4 does not fit the paradigm of TRAF function in immune and
      inflammatory responses. Its physiological and molecular functions remain poorly
      understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit
      altered locomotion coordination typical of ataxia. TRAF4-KO central nervous
      system (CNS) ultrastructure shows strong myelin perturbation including
      disorganized layers and disturbances in paranode organization. TRAF4 was
      previously reported to be expressed by CNS neurons. Using primary cell culture,
      we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of
      their differentiation. Moreover, histology and electron microscopy show
      degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was
      confirmed by increased expression of the Bax pro-apoptotic marker
      (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage
      (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin
      induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR
      were overexpressed (Q-RT-PCR and western blotting). The strong increased
      phosphorylation of Rock2, a RhoA downstream target, indicated that the
      NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton
      rearrangement that favors axon regeneration inhibition and neuron apoptosis, is
      activated in the absence of TRAF4 (western blotting). Altogether, these results
      provide conclusive evidence for the pivotal contribution of TRAF4 to myelination
      and to cerebellar homeostasis, and link the loss of TRAF4 function to
      demyelinating or neurodegenerative diseases.

PMID- 22363516
TI  - Changing domesticity of Aedes aegypti in northern peninsular Malaysia:
      reproductive consequences and potential epidemiological implications.
AB  - BACKGROUND: The domestic dengue vector Aedes aegypti mosquitoes breed in indoor
      containers. However, in northern peninsular Malaysia, they show equal preference
      for breeding in both indoor and outdoor habitats. To evaluate the epidemiological
      implications of this peridomestic adaptation, we examined whether Ae. aegypti
      exhibits decreased survival, gonotrophic activity, and fecundity due to lack of
      host availability and the changing breeding behavior. METHODOLOGY/PRINCIPAL
      FINDINGS: This yearlong field surveillance identified Ae. aegypti breeding in
      outdoor containers on an enormous scale. Through a sequence of experiments
      incorporating outdoors and indoors adapting as well as adapted populations, we
      observed that indoors provided better environment for the survival of Ae. aegypti
      and the observed death patterns could be explained on the basis of a difference
      in body size. The duration of gonotrophic period was much shorter in large-bodied
      females. Fecundity tended to be greater in indoor acclimated females. We also
      found increased tendency to multiple feeding in outdoors adapted females, which
      were smaller in size compared to their outdoors breeding counterparts.
      CONCLUSION/SIGNIFICANCE: The data presented here suggest that acclimatization of
      Ae. aegypti to the outdoor environment may not decrease its lifespan or
      gonotrophic activity but rather increase breeding opportunities (increased number
      of discarded containers outdoors), the rate of larval development, but small body
      sizes at emergence. Size is likely to be correlated with disease transmission. In
      general, small size in Aedes females will favor increased blood-feeding frequency
      resulting in higher population sizes and disease occurrence.

PMID- 22363517
TI  - The cerebro-morphological fingerprint of a progeroid syndrome: white matter
      changes correlate with neurological symptoms in xeroderma pigmentosum.
AB  - BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid
      syndrome. It has recently been shown that the underlying DNA repair defect plays
      a central role in the aging process. In addition to skin symptoms, various
      premature neurological abnormalities have been reported. METHODOLOGY/PRINCIPAL
      FINDINGS: We present the clinical neurological phenotype in 14 XP patients (seven
      subtypes), in seven of these patients together with conventional and
      multiparametric advanced MRI data to assess the macrostructural and
      microstructural cerebral morphology in comparison to controls, including
      volumetric measurements, MR spectroscopy ((1)H MRS), and diffusion tensor imaging
      (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and
      mild cognitive deficits. DTI demonstrated significantly reduced WM directionality
      in all regions investigated, i.e. the thalamus, the corticospinal tracts and the
      dorsal corpus callosum. Single patients showed a marked relative hippocampal
      volume reduction, but the patients were not different from controls in the
      volumetric measurements of hippocampal and whole brain volumes at group level.
      However, (1)H MRS demonstrated that the hippocampal formation was metabolically
      altered. CONCLUSIONS: The most prominent feature was the white matter
      affectation, as assessed by DTI, with volume and directionality reductions of the
      fiber projections involving both the craniocaudal fibers and the interhemispheric
      connections. These findings, although heterogeneous among the study sample, could
      be correlated with the clinico-neurological symptoms. The imaging findings
      support the position that myelin structures degrade prematurely in the brain of
      XP patients.

PMID- 22363518
TI  - A putative P-type ATPase required for virulence and resistance to haem toxicity
      in Listeria monocytogenes.
AB  - Regulation of iron homeostasis in many pathogens is principally mediated by the
      ferric uptake regulator, Fur. Since acquisition of iron from the host is
      essential for the intracellular pathogen Listeria monocytogenes, we predicted the
      existence of Fur-regulated systems that support infection. We examined the
      contribution of nine Fur-regulated loci to the pathogenicity of L. monocytogenes
      in a murine model of infection. While mutating the majority of the genes failed
      to affect virulence, three mutants exhibited a significantly compromised
      virulence potential. Most striking was the role of the membrane protein we
      designate FrvA (Fur regulated virulence factor A; encoded by frvA [lmo0641]),
      which is absolutely required for the systemic phase of infection in mice and also
      for virulence in an alternative infection model, the Wax Moth Galleria
      mellonella. Further analysis of the DeltafrvA mutant revealed poor growth in iron
      deficient media and inhibition of growth by micromolar concentrations of haem or
      haemoglobin, a phenotype which may contribute to the attenuated growth of this
      mutant during infection. Uptake studies indicated that the DeltafrvA mutant is
      unaffected in the uptake of ferric citrate but demonstrates a significant
      increase in uptake of haem and haemin. The data suggest a potential role for FrvA
      as a haem exporter that functions, at least in part, to protect the cell against
      the potential toxicity of free haem.

PMID- 22363519
TI  - Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy receptor
      with high binding affinity for a target protein.
AB  - Repeat proteins are increasingly attracting much attention as alternative
      scaffolds to immunoglobulin antibodies due to their unique structural features.
      Nonetheless, engineering interaction interface and understanding molecular basis
      for affinity maturation of repeat proteins still remain a challenge. Here, we
      present a structure-based rational design of a repeat protein with high binding
      affinity for a target protein. As a model repeat protein, a Toll-like receptor4
      (TLR4) decoy receptor composed of leucine-rich repeat (LRR) modules was used, and
      its interaction interface was rationally engineered to increase the binding
      affinity for myeloid differentiation protein 2 (MD2). Based on the complex
      crystal structure of the decoy receptor with MD2, we first designed single amino
      acid substitutions in the decoy receptor, and obtained three variants showing a
      binding affinity (K(D)) one-order of magnitude higher than the wild-type decoy
      receptor. The interacting modes and contributions of individual residues were
      elucidated by analyzing the crystal structures of the single variants. To further
      increase the binding affinity, single positive mutations were combined, and two
      double mutants were shown to have about 3000- and 565-fold higher binding
      affinities than the wild-type decoy receptor. Molecular dynamics simulations and
      energetic analysis indicate that an additive effect by two mutations occurring at
      nearby modules was the major contributor to the remarkable increase in the
      binding affinities.

PMID- 22363520
TI  - Analysis of the global ocean sampling (GOS) project for trends in iron uptake by
      surface ocean microbes.
AB  - Microbial metagenomes are DNA samples of the most abundant, and therefore most
      successful organisms at the sampling time and location for a given cell size
      range. The study of microbial communities via their DNA content has
      revolutionized our understanding of microbial ecology and evolution. Iron
      availability is a critical resource that limits microbial communities' growth in
      many oceanic areas. Here, we built a database of 2319 sequences, corresponding to
      140 gene families of iron metabolism with a large phylogenetic spread, to explore
      the microbial strategies of iron acquisition in the ocean's bacterial community.
      We estimate iron metabolism strategies from metagenome gene content and
      investigate whether their prevalence varies with dissolved iron concentrations
      obtained from a biogeochemical model. We show significant quantitative and
      qualitative variations in iron metabolism pathways, with a higher proportion of
      iron metabolism genes in low iron environments. We found a striking difference
      between coastal and open ocean sites regarding Fe(2+) versus Fe(3+) uptake gene
      prevalence. We also show that non-specific siderophore uptake increases in low
      iron open ocean environments, suggesting bacteria may acquire iron from natural
      siderophore-like organic complexes. Despite the lack of knowledge of iron uptake
      mechanisms in most marine microorganisms, our approach provides insights into how
      the iron metabolic pathways of microbial communities may vary with seawater iron
      concentrations.

PMID- 22363521
TI  - Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009
      influenza virus in Japan between 2009 and 2010.
AB  - BACKGROUND: In April 2009, a novel swine-derived influenza A virus (H1N1pdm)
      emerged and rapidly spread around the world, including Japan. It has been
      suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid
      receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses,
      which have a predilection for 2,6-linked sialic acid. METHODS/RESULTS: To
      elucidate the existence and transmissibility of alpha2,3 sialic acid-specific
      viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules
      were investigated, especially D187E, D222G, and Q223R, which are related to a
      shift from human to avian receptor specificity. Samples from individuals infected
      during the first and second waves of the outbreak in Japan were examined using a
      high-throughput sequencing approach. In May 2009, three specimens from mild cases
      showed D222G and/or Q223R substitutions in a minor subpopulation of viruses
      infecting these individuals. However, the substitutions almost disappeared in the
      samples from five mild cases in December 2010. The D187E substitution was not
      widespread in specimens, even in May 2009. CONCLUSIONS: These results suggest
      that alpha2,3 sialic acid-specific viruses, including G222 and R223, existed in
      humans as a minor population in the early phase of the pandemic, and that D222
      and Q223 became more dominant through human-to-human transmission during the
      first and second waves of the epidemic. These results are consistent with the low
      substitution rates identified in seasonal H1N1 viruses in 2008.

PMID- 22363522
TI  - Rice phospholipase A superfamily: organization, phylogenetic and expression
      analysis during abiotic stresses and development.
AB  - BACKGROUND: Phospholipase A (PLA) is an important group of enzymes responsible
      for phospholipid hydrolysis in lipid signaling. PLAs have been implicated in
      abiotic stress signaling and developmental events in various plants species.
      Genome-wide analysis of PLA superfamily has been carried out in dicot plant
      Arabidopsis. A comprehensive genome-wide analysis of PLAs has not been presented
      yet in crop plant rice. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive
      bioinformatics analysis identified a total of 31 PLA encoding genes in the rice
      genome, which are divided into three classes; phospholipase A(1) (PLA(1)),
      patatin like phospholipases (pPLA) and low molecular weight secretory
      phospholipase A(2) (sPLA(2)) based on their sequences and phylogeny. A subset of
      10 rice PLAs exhibited chromosomal duplication, emphasizing the role of
      duplication in the expansion of this gene family in rice. Microarray expression
      profiling revealed a number of PLA members expressing differentially and
      significantly under abiotic stresses and reproductive development. Comparative
      expression analysis with Arabidopsis PLAs revealed a high degree of functional
      conservation between the orthologs in two plant species, which also indicated the
      vital role of PLAs in stress signaling and plant development across different
      plant species. Moreover, sub-cellular localization of a few candidates suggests
      their differential localization and functional role in the lipid signaling.
      CONCLUSION/SIGNIFICANCE: The comprehensive analysis and expression profiling
      would provide a critical platform for the functional characterization of the
      candidate PLA genes in crop plants.

PMID- 22363524
TI  - Evidence for weak or linear conformity but not for hyper-conformity in an
      everyday social learning context.
AB  - Conformity is thought to be an important force in cultural evolution because it
      has the potential to stabilize cooperation in large groups, potentiate group
      selection and thus explain uniquely human behaviors. However, the effects of such
      conformity on cultural and biological evolution will depend much on the way
      individuals are influenced by the frequency of alternative behavioral options
      witnessed. Theoretical modeling has suggested that only what we refer to as
      'hyper-conformity', an exaggerated tendency to perform the most frequent behavior
      witnessed in other individuals, is able to increase within-group homogeneity and
      between-group diversity, for instance. Empirically however, few experiments have
      addressed how the frequency of behavior witnessed affects behavior. Accordingly
      we performed an experiment to test for the presence of conformity in a natural
      situation with humans. Visitors to a Zoo exhibit were invited to write or draw
      answers to questions on A5 cards and potentially win a small prize. We
      manipulated the proportion of existing writings versus drawings visible to
      visitors and measured the proportion of written cards submitted. We found a
      strong and significant effect of the proportion of text displayed on the
      proportion of text in the answers, thus demonstrating social learning. We show
      that this effect is approximately linear, with potentially a small, weak
      conformist component but no hyper-conformist one. The present experiment
      therefore provides evidence for linear conformity in humans in a very natural
      context.

PMID- 22363523
TI  - Role of position 627 of PB2 and the multibasic cleavage site of the hemagglutinin
      in the virulence of H5N1 avian influenza virus in chickens and ducks.
AB  - Highly pathogenic H5N1 avian influenza viruses have caused major disease
      outbreaks in domestic and free-living birds with transmission to humans resulting
      in 59% mortality amongst 564 cases. The mutation of the amino acid at position
      627 of the viral polymerase basic-2 protein (PB2) from glutamic acid (E) in avian
      isolates to lysine (K) in human isolates is frequently found, but it is not known
      if this change affects the fitness and pathogenicity of the virus in birds. We
      show here that horizontal transmission of A/Vietnam/1203/2004 H5N1 (VN/1203)
      virus in chickens and ducks was not affected by the change of K to E at PB2-627.
      All chickens died between 21 to 48 hours post infection (pi), while 70% of the
      ducks survived infection. Virus replication was detected in chickens within 12
      hours pi and reached peak titers in spleen, lung and brain between 18 to 24 hours
      for both viruses. Viral antigen in chickens was predominantly in the endothelium,
      while in ducks it was present in multiple cell types, including neurons,
      myocardium, skeletal muscle and connective tissues. Virus replicated to a high
      titer in chicken thrombocytes and caused upregulation of TLR3 and several cell
      adhesion molecules, which may explain the rapid virus dissemination and location
      of viral antigen in endothelium. Virus replication in ducks reached peak values
      between 2 and 4 days pi in spleen, lung and brain tissues and in contrast to
      infection in chickens, thrombocytes were not involved. In addition, infection of
      chickens with low pathogenic VN/1203 caused neuropathology, with E at position
      PB2-627 causing significantly higher infection rates than K, indicating that it
      enhances virulence in chickens.

PMID- 22363525
TI  - The Aspergillus nidulans kinesin-3 tail is necessary and sufficient to recognize
      modified microtubules.
AB  - Posttranslational microtubule modifications (PTMs) are numerous; however, the
      biochemical and cell biological roles of those modifications remain mostly an
      enigma. The Aspergillus nidulans kinesin-3 UncA uses preferably modified
      microtubules (MTs) as tracks for vesicle transportation. Here, we show that a
      positively charged region in the tail of UncA (amino acids 1316 to 1402) is
      necessary for the recognition of modified MTs. Chimeric proteins composed of the
      kinesin-1 motor domain and the UncA tail displayed the same specificity as UncA,
      suggesting that the UncA tail is sufficient to establish specificity. Interaction
      between the UncA tail and alpha-tubulin was shown using a yeast two-hybrid assay
      and in A. nidulans by bimolecular fluorescence complementation. This is the first
      demonstration of how a kinesin-3 motor protein distinguishes among different MT
      populations in fungal cells, and how specificity determination depends on the
      tail rather than the motor domain, as has been demonstrated for kinesin 1 in
      neuronal cells.

PMID- 22363526
TI  - Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity
      and acute stress using the phase response curve.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone
      signalling system that regulates the pulsatile secretion of glucocorticoids from
      the adrenal glands. In addition to regulation of basal levels of glucocorticoids,
      the HPA axis provides a rapid hormonal response to stress that is vitally
      important for homeostasis. Recently it has become clear that glucocorticoid
      pulses encode an important biological signal that regulates receptor signalling
      both in the central nervous system and in peripheral tissues. It is therefore
      important to understand how stressful stimuli disrupt the pulsatile dynamics of
      this system. Using a computational model that incorporates the crucial feed
      forward and feedback components of the axis, we provide novel insight into
      experimental observations that the size of the stress-induced hormonal response
      is critically dependent on the timing of the stress. Further, we employ the
      theory of Phase Response Curves to show that an acute stressor acts as a phase
      resetting mechanism for the ultradian rhythm of glucocorticoid secretion. Using
      our model, we demonstrate that the magnitude of an acute stress is a critical
      factor in determining whether the system resets via a Type 1 or Type 0 mechanism.
      By fitting our model to our in vivo stress-response data, we show that the
      glucocorticoid response to an acute noise stress in rats is governed by a Type 0
      phase-resetting curve. Our results provide additional evidence for the concept of
      a deterministic sub-hypothalamic oscillator regulating the ultradian
      glucocorticoid rhythm, which constitutes a highly responsive peripheral hormone
      system that interacts dynamically with hypothalamic inputs to regulate the
      overall hormonal response to stress.

PMID- 22363527
TI  - A new method for species identification via protein-coding and non-coding DNA
      barcodes by combining machine learning with bioinformatic methods.
AB  - Species identification via DNA barcodes is contributing greatly to current
      bioinventory efforts. The initial, and widely accepted, proposal was to use the
      protein-coding cytochrome c oxidase subunit I (COI) region as the standard
      barcode for animals, but recently non-coding internal transcribed spacer (ITS)
      genes have been proposed as candidate barcodes for both animals and plants.
      However, achieving a robust alignment for non-coding regions can be problematic.
      Here we propose two new methods (DV-RBF and FJ-RBF) to address this issue for
      species assignment by both coding and non-coding sequences that take advantage of
      the power of machine learning and bioinformatics. We demonstrate the value of the
      new methods with four empirical datasets, two representing typical protein-coding
      COI barcode datasets (neotropical bats and marine fish) and two representing non
      coding ITS barcodes (rust fungi and brown algae). Using two random sub-sampling
      approaches, we demonstrate that the new methods significantly outperformed
      existing Neighbor-joining (NJ) and Maximum likelihood (ML) methods for both
      coding and non-coding barcodes when there was complete species coverage in the
      reference dataset. The new methods also out-performed NJ and ML methods for non
      coding sequences in circumstances of potentially incomplete species coverage,
      although then the NJ and ML methods performed slightly better than the new
      methods for protein-coding barcodes. A 100% success rate of species
      identification was achieved with the two new methods for 4,122 bat queries and
      5,134 fish queries using COI barcodes, with 95% confidence intervals (CI) of
      99.75-100%. The new methods also obtained a 96.29% success rate (95%CI: 91.62
      98.40%) for 484 rust fungi queries and a 98.50% success rate (95%CI: 96.60
      99.37%) for 1094 brown algae queries, both using ITS barcodes.

PMID- 22363528
TI  - De novo transcriptome of safflower and the identification of putative genes for
      oleosin and the biosynthesis of flavonoids.
AB  - Safflower (Carthamus tinctorius L.) is one of the most extensively used oil crops
      in the world. However, little is known about how its compounds are synthesized at
      the genetic level. In this study, Solexa-based deep sequencing on seed, leaf and
      petal of safflower produced a de novo transcriptome consisting of 153,769
      unigenes. We annotated 82,916 of the unigenes with gene annotation and assigned
      functional terms and specific pathways to a subset of them. Metabolic pathway
      analysis revealed that 23 unigenes were predicted to be responsible for the
      biosynthesis of flavonoids and 8 were characterized as seed-specific oleosins. In
      addition, a large number of differentially expressed unigenes, for example, those
      annotated as participating in anthocyanin and chalcone synthesis, were predicted
      to be involved in flavonoid biosynthesis pathways. In conclusion, the de novo
      transcriptome investigation of the unique transcripts provided candidate gene
      resources for studying oleosin-coding genes and for investigating genes related
      to flavonoid biosynthesis and metabolism in safflower.

PMID- 22363529
TI  - Insecticide resistance in the dengue vector Aedes aegypti from Martinique:
      distribution, mechanisms and relations with environmental factors.
AB  - Dengue is an important mosquito borne viral disease in Martinique Island (French
      West Indies). The viruses responsible for dengue are transmitted by Aedes
      aegypti, an indoor day-biting mosquito. The most effective proven method for
      disease prevention has been by vector control by various chemical or biological
      means. Unfortunately insecticide resistance has already been observed on the
      Island and recently showed to significantly reduce the efficacy of vector control
      interventions. In this study, we investigated the distribution of resistance and
      the underlying mechanisms in nine Ae. aegypti populations. Statistical
      multifactorial approach was used to investigate the correlations between
      insecticide resistance levels, associated mechanisms and environmental factors
      characterizing the mosquito populations. Bioassays revealed high levels of
      resistance to temephos and deltamethrin and susceptibility to Bti in the 9
      populations tested. Biochemical assays showed elevated detoxification enzyme
      activities of monooxygenases, carboxylesterases and glutathione S-tranferases in
      most of the populations. Molecular screening for common insecticide target-site
      mutations, revealed the presence of the "knock-down resistance" V1016I Kdr
      mutation at high frequency (>87%). Real time quantitative RT-PCR showed the
      potential involvement of several candidate detoxification genes in insecticide
      resistance. Principal Component Analysis (PCA) performed with variables
      characterizing Ae. aegypti from Martinique permitted to underline potential links
      existing between resistance distribution and other variables such as agriculture
      practices, vector control interventions and urbanization. Insecticide resistance
      is widespread but not homogeneously distributed across Martinique. The influence
      of environmental and operational factors on the evolution of the resistance and
      mechanisms are discussed.

PMID- 22363531
TI  - Ethnic differences in survival after breast cancer in South East Asia.
AB  - BACKGROUND: The burden of breast cancer in Asia is escalating. We evaluated the
      impact of ethnicity on survival after breast cancer in the multi-ethnic region of
      South East Asia. METHODOLOGY/PRINCIPAL FINDINGS: Using the Singapore-Malaysia
      hospital-based breast cancer registry, we analyzed the association between
      ethnicity and mortality following breast cancer in 5,264 patients diagnosed
      between 1990 and 2007 (Chinese: 71.6%, Malay: 18.4%, Indian: 10.0%). We compared
      survival rates between ethnic groups and calculated adjusted hazard ratios (HR)
      to estimate the independent effect of ethnicity on survival. Malays (n = 968)
      presented at a significantly younger age, with larger tumors, and at later stages
      than the Chinese and Indians. Malays were also more likely to have axillary lymph
      node metastasis at similar tumor sizes and to have hormone receptor negative and
      poorly differentiated tumors. Five year overall survival was highest in the
      Chinese women (75.8%; 95%CI: 74.4%-77.3%) followed by Indians (68.0%; 95%CI:
      63.8%-72.2%), and Malays (58.5%; 95%CI: 55.2%-61.7%). Compared to the Chinese,
      Malay ethnicity was associated with significantly higher risk of all-cause
      mortality (HR: 1.34; 95%CI: 1.19-1.51), independent of age, stage, tumor
      characteristics and treatment. Indian ethnicity was not significantly associated
      with risk of mortality after breast cancer compared to the Chinese (HR: 1.14;
      95%CI: 0.98-1.34). CONCLUSION: In South East Asia, Malay ethnicity is
      independently associated with poorer survival after breast cancer. Research into
      underlying reasons, potentially including variations in tumor biology,
      psychosocial factors, treatment responsiveness and lifestyle after diagnosis, is
      warranted.

PMID- 22363530
TI  - Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1)
      are associated with breast cancer metastasis and decreased survival.
AB  - BACKGROUND: Breast cancer is the most common malignancy among women worldwide in
      terms of incidence and mortality. About 10% of North American women will be
      diagnosed with breast cancer during their lifetime and 20% of those will die of
      the disease. Breast cancer is a heterogeneous disease and biomarkers able to
      correctly classify patients into prognostic groups are needed to better tailor
      treatment options and improve outcomes. One powerful method used for biomarker
      discovery is sample screening with mass spectrometry, as it allows direct
      comparison of protein expression between normal and pathological states. The
      purpose of this study was to use a systematic and objective method to identify
      biomarkers with possible prognostic value in breast cancer patients, particularly
      in identifying cases most likely to have lymph node metastasis and to validate
      their prognostic ability using breast cancer tissue microarrays. METHODS AND
      FINDINGS: Differential proteomic analyses were employed to identify candidate
      biomarkers in primary breast cancer patients. These analyses identified decorin
      (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour
      microenvironment and in pathways related to tumorigenesis. This study indicates
      that high expression of Decorin is associated with lymph node metastasis
      (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall
      survival (p = 0.01). High expression of HSP90B1 is associated with distant
      metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients
      also appear to benefit significantly from hormonal treatment. CONCLUSIONS: Using
      quantitative proteomic profiling of primary breast cancers, two new promising
      prognostic and predictive markers were found to identify patients with worse
      survival. In addition HSP90B1 appears to identify a group of patients with
      distant metastasis with otherwise good prognostic features.

PMID- 22363532
TI  - Circulating antinuclear antibodies in patients with pelvic masses are associated
      with malignancy and decreased survival.
AB  - BACKGROUND: Circulating autoantibodies occur more frequently in cancer patients
      than in patients without cancer. METHODS AND FINDINGS: We examined sera from
      patients referred for pelvic mass symptoms to a tertiary university clinic. A
      total of 127 were diagnosed with epithelial ovarian cancer while 386 had a benign
      condition. A screen for IgG anti-nuclear antibodies (ANA) by indirect
      immunofluorescence on HEp-2 cells confirmed a highly significant
      overrepresentation of ANA in the cancer group where 40% had detectable (i.e., a
      titer >=160) ANA compared with less than 12% in the benign group. The
      overrepresentation of ANA in the cancer group persisted (p<0.0001) after matching
      the age-profile of the benign group with the ovarian cancer group. Only 19 out of
      127 patients in the age-matched benign subgroup were positive for ANA
      corresponding to an 85% specificity at 40% sensitivity of ANA as the only marker
      for malignancy. No correlation of ANA positivity in either group with specific
      bands in immunoblots could be demonstrated even though immunoblot positivity was
      clearly increased in the malignant group (41% vs. 3%). The presence, strength,
      and type of ANA did not correlate with serum CA-125 values or with staging, and
      ANA outcome did not contribute with independent diagnostic information. However,
      survival was significantly shorter in ANA-positive compared with ANA-negative
      cancer patients and patients with CA-125 below the median CA-125 value in the
      cancer group had a significantly decreased survival when positive for ANA. ANA
      status made no difference in the group with CA-125 values above the median. Also,
      there was a significant correlation between speckled ANA-strength and
      histological tumor grade. CONCLUSIONS: Circulating antibodies are a promising
      source for new biomarkers in cancer. Characterization of epitope specificities
      and measurements of consecutive samples will be important for further elucidating
      the role of ANA in evaluating ovarian cancer patients.

PMID- 22363533
TI  - Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint
      control.
AB  - In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid
      tumors or myeloproliferative disorders, the product of the normal allele is
      supposed to be functionally impaired or absent. To address the consequence of the
      loss of CCDC6 expression, we applied lentiviral shRNA in several cell lines. Loss
      of CCDC6 resulted in increased cell death with clear shortening of the S phase
      transition of the cell cycle. Upon exposure to etoposide, the cells lacking CCDC6
      did not achieve S-phase accumulation. In the absence of CCDC6 and in the presence
      of genotoxic stress, like etoposide treatment or UV irradiation, increased
      accumulation of DNA damage was observed, as indicated by a significant increase
      of pH2Ax Ser139. 14-3-3sigma, a major cell cycle regulator, was down-regulated in
      CCDC6 lacking cells, regardless of genotoxic stress. Interestingly, in the
      absence of CCDC6, the well-known genotoxic stress-induced cytoplasmic
      sequestration of the S-phase checkpoint CDC25C phosphatase did not occur. These
      observations suggest that CCDC6 plays a key role in cell cycle control,
      maintenance of genomic stability and cell survival and provide a rational of how
      disruption of CCDC6 normal function contributes to malignancy.

PMID- 22363534
TI  - An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3
      kinase protects against cerebral malaria.
AB  - Cerebral malaria (CM) is a lethal neurological complication of malaria. We
      implemented a genome-wide screen in mutagenized mice to identify host proteins
      involved in CM pathogenesis and whose inhibition may be of therapeutic value. One
      pedigree (P48) segregated a resistance trait whose CM-protective effect was fully
      penetrant, mapped to chromosome 8, and identified by genome sequencing as
      homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus
      associated kinase 3 (Jak3). The causative effect of Jak3(W81R) was verified by
      complementation testing in Jak3(W81R/-) double heterozygotes that were fully
      protected against CM. Jak3(W81R) homozygotes showed defects in thymic development
      with depletion of CD8(+) T cell, B cell, and NK cell compartments, and defective
      T cell-dependent production of IFN-gamma. Adoptive transfer of normal splenocytes
      abrogates CM resistance in Jak3(W81R) homozygotes, an effect attributed to the
      CD8(+) T cells. Jak3(W81R) behaves as a dominant negative variant, with
      significant CM resistance of Jak3(W81R/+) heterozygotes, compared to CM
      susceptible Jak3(+/+) and Jak3(+/-) controls. CM resistance in Jak3(W81R/+)
      heterozygotes occurs in presence of normal T, B and NK cell numbers. These
      findings highlight the pathological role of CD8(+) T cells and Jak3-dependent IFN
      gamma-mediated Th1 responses in CM pathogenesis.

PMID- 22363536
TI  - DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and
      specific association with the presence of intrathecal IgM bands.
AB  - BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease with a genetic
      basis. The strongest associations with the disease lie in the Human Leukocyte
      Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk
      factor associated to MS so far, no consistent effect has been described for any
      other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across
      populations and studies. We postulate that those discrepancies could be due to
      differences in the diverse haplotypes bearing that allele. Thus, we aimed at
      studying the association of DRB1*03:01 with MS susceptibility considering this
      allele globally and stratified by haplotypes. We also evaluated the association
      with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in
      cerebrospinal fluid. METHODS: Genotyping of HLA-B, -DRB1 and -DQA1 was performed
      in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and
      thirty-nine MS patients were classified according to the presence (M+, 58
      patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS
      patients vs. controls and M+ vs. M-) were performed with the chi-square test or
      the Fisher exact test. RESULTS: Association of DRB1*03:01 with MS susceptibility
      was observed but with different haplotypic contribution, being the ancestral
      haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M-
      and controls showed that the AH 18.2 was affecting only M+ individuals,
      conferring a risk similar to that caused by DRB1*15:01. CONCLUSIONS: The diverse
      DRB1*03:01-containing haplotypes contribute with different risk to MS
      susceptibility. The AH 18.2 causes the highest risk and affects only to
      individuals showing OCMB.

PMID- 22363535
TI  - Analysis of the Tomato spotted wilt virus ambisense S RNA-encoded hairpin
      structure in translation.
AB  - BACKGROUND: The intergenic region (IR) of ambisense RNA segments from animal- and
      plant-infecting (-)RNA viruses functions as a bidirectional transcription
      terminator. The IR sequence of the Tomato spotted wilt virus (TSWV) ambisense S
      RNA contains stretches that are highly rich in A-residues and U-residues and is
      predicted to fold into a stable hairpin structure. The presence of this hairpin
      structure sequence in the 3' untranslated region (UTR) of TSWV mRNAs implies a
      possible role in translation. METHODOLOGY/PRINCIPAL FINDINGS: To analyse the role
      of the predicted hairpin structure in translation, various Renilla luciferase
      constructs containing modified 3' and/or 5' UTR sequences of the TSWV S RNA
      encoded nucleocapsid (N) gene were analyzed for expression. While good luciferase
      expression levels were obtained from constructs containing the 5' UTR and the 3'
      UTR, luciferase expression was lost when the hairpin structure sequence was
      removed from the 3' UTR. Constructs that only lacked the 5' UTR, still rendered
      good expression levels. When in addition the entire 3' UTR was exchanged for that
      of the S RNA encoded non-structural (NSs) gene transcript, containing the
      complementary hairpin folding sequence, the loss of luciferase expression could
      only be recovered by providing the 5' UTR sequence of the NSs transcript.
      Luciferase activity remained unaltered when the hairpin structure sequence was
      swapped for the analogous one from Tomato yellow ring virus, another distinct
      tospovirus. The addition of N and NSs proteins further increased luciferase
      expression levels from hairpin structure containing constructs.
      CONCLUSIONS/SIGNIFICANCE: The results suggest a role for the predicted hairpin
      structure in translation in concert with the viral N and NSs proteins. The
      presence of stretches highly rich in A-residues does not rule out a concerted
      action with a poly(A)-tail-binding protein. A common transcription termination
      and translation strategy for plant- and animal-infecting ambisense RNA viruses is
      being discussed.

PMID- 22363537
TI  - A potential regulatory role for intronic microRNA-338-3p for its host gene
      encoding apoptosis-associated tyrosine kinase.
AB  - MicroRNAs (miRNAs) are important gene regulators that are abundantly expressed in
      both the developing and adult mammalian brain. These non-coding gene transcripts
      are involved in post-transcriptional regulatory processes by binding to specific
      target mRNAs. Approximately one third of known miRNA genes are located within
      intronic regions of protein coding and non-coding regions, and previous studies
      have suggested a role for intronic miRNAs as negative feedback regulators of
      their host genes. In the present study, we monitored the dynamic gene expression
      changes of the intronic miR-338-3p and miR-338-5p and their host gene Apoptosis
      associated Tyrosine Kinase (AATK) during the maturation of rat hippocampal
      neurons. This revealed an uncorrelated expression pattern of mature miR-338
      strands with their host gene. Sequence analysis of the 3' untranslated region
      (UTR) of rat AATK mRNA revealed the presence of two putative binding sites for
      miR-338-3p. Thus, miR-338-3p may have the capacity to modulate AATK mRNA levels
      in neurons. Transfection of miR-338-3p mimics into rat B35 neuroblastoma cells
      resulted in a significant decrease of AATK mRNA levels, while the transfection of
      synthetic miR-338-5p mimics did not alter AATK levels. Our results point to a
      possible molecular mechanism by which miR-338-3p participates in the regulation
      of its host gene by modulating the levels of AATK mRNA, a kinase which plays a
      role during differentiation, apoptosis and possibly in neuronal degeneration.

PMID- 22363538
TI  - Changes in the brain microstructure of children with primary monosymptomatic
      nocturnal enuresis: a diffusion tensor imaging study.
AB  - BACKGROUND: Primary monosymptomatic nocturnal enuresis (PMNE) is a common
      disorder in school-aged children. Previous studies have suggested that a
      developmental delay might play a role in the pathology of children with PMNE.
      However, microstructural abnormalities in the brains of these children have not
      been thoroughly investigated. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we
      evaluated structural changes in the brains of children with PMNE using diffusion
      tensor imaging (DTI). Two groups consisting of 26 children with PMNE and 26
      healthy controls were scanned using magnetic resonance DTI. The diffusion
      parameters of fractional anisotropy (FA) and mean diffusivity (MD) were subjected
      to whole-brain, voxel-wise group comparisons using statistical parametric mapping
      (SPM). When compared to healthy subjects, children with PMNE showed both a
      decrease in FA and an increase in MD in the thalamus. MD also increased in the
      frontal lobe, the anterior cingulate cortex and the insula; these areas are all
      involved in controlling micturition. The significant changes seen in the thalamus
      could affect both urine storage and arousal from sleep. CONCLUSIONS/SIGNIFICANCE:
      The microstructure abnormalities were observed in the thalamus, the medial
      frontal gyrus, the anterior cingulate cortex and the insula, which are involved
      in micturition control network. This indicates developmental delay in these areas
      may be the cause of PMNE.

PMID- 22363540
TI  - Genomic position mapping discrepancies of commercial SNP chips.
AB  - The field of genetics has come to rely heavily on commercial genotyping arrays
      and accompanying annotations for insights into genotype-phenotype associations.
      However, in order to avoid errors and false leads, it is imperative that the
      annotation of SNP chromosomal positions is accurate and unambiguous. We report on
      genomic positional discrepancies of various SNP chips for human, cattle and mouse
      species, and discuss their causes and consequences.

PMID- 22363539
TI  - Disease-toxicant interactions in manganese exposed Huntington disease mice: early
      changes in striatal neuron morphology and dopamine metabolism.
AB  - YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn)
      in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn
      and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the
      level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128
      mice were exposed to MnCl(2)-4H(2)O (50 mg/kg) on days 0, 3 and 6. Striatal
      medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its
      metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13
      weeks (7 days from initial exposure) and 16 weeks (28 days from initial
      exposure). No genotype-dependent differences in MSN morphology were apparent at
      13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice,
      manifested by an absence of the wild-type age-dependent increase in dendritic
      length and branching complexity. In addition, genotype-exposure interaction
      effects were observed for dendritic complexity measures as a function of distance
      from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore,
      striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at
      16 weeks, both Mn exposure and the HD genotype were associated with
      quantitatively similar reductions in DA and its metabolites. Interestingly, Mn
      exposure of YAC128 mice did not further decrease DA or its metabolites versus
      YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results
      demonstrate Mn-HD disease-toxicant interactions at the onset of striatal
      dendritic neuropathology in YAC128 mice. Our results identify the earliest
      pathological change in striatum of YAC128 mice as being between 13 to 16 weeks.
      Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as
      decreased DA levels, while it exacerbates others, such as dendritic pathology.

PMID- 22363542
TI  - Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana
      (Poaceae: Triticeae) affected by environmental factors.
AB  - Polyploidization is a major evolutionary process. Approximately 70-75% species of
      Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate
      intergenomic rearrangements after polyploidization of Triticeae species and to
      determine the effects of environmental factors on them, nine populations of a
      typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al.
      (2n = 6x = 42, StStPPYY), collected from different environments, were studied
      using genome in situ hybridization (GISH). We found that intergenomic
      rearrangements occurred between the relatively large P genome and the small
      genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of
      translocations compared to their diploid progenitors. However, no translocation
      was found between the relatively small St and Y chromosomes. Environmental
      factors may affect rearrangements among the three genomes. Chromosome
      translocations were significantly more frequent in populations from cold alpine
      and grassland environments than in populations from valley and lake-basin
      habitats (P<0.05). The relationship between types of chromosome translocations
      and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements
      associated with environmental factors and genetic differentiation of a single
      basic genome should be considered as equally important genetic processes during
      species' ecotype evolution.

PMID- 22363541
TI  - Identification and characterization of a novel calcium-activated apyrase from
      Cryptosporidium parasites and its potential role in pathogenesis.
AB  - Herein, we report the biochemical and functional characterization of a novel
      Ca(2+)-activated nucleoside diphosphatase (apyrase), CApy, of the intracellular
      gut pathogen Cryptosporidium. The purified recombinant CApy protein displayed
      activity, substrate specificity and calcium dependency strikingly similar to the
      previously described human apyrase, SCAN-1 (soluble calcium-activated
      nucleotidase 1). CApy was found to be expressed in both Cryptosporidium parvum
      oocysts and sporozoites, and displayed a polar localization in the latter,
      suggesting a possible co-localization with the apical complex of the parasite. In
      vitro binding experiments revealed that CApy interacts with the host cell in a
      dose-dependent fashion, implying the presence of an interacting partner on the
      surface of the host cell. Antibodies directed against CApy block Cryptosporidium
      parvum sporozoite invasion of HCT-8 cells, suggesting that CApy may play an
      active role during the early stages of parasite invasion. Sequence analyses
      revealed that the capy gene shares a high degree of homology with apyrases
      identified in other organisms, including parasites, insects and humans.
      Phylogenetic analysis argues that the capy gene is most likely an ancestral
      feature that has been lost from most apicomplexan genomes except Cryptosporidium,
      Neospora and Toxoplasma.

PMID- 22363543
TI  - Two novel mutations in the EYS gene are possible major causes of autosomal
      recessive retinitis pigmentosa in the Japanese population.
AB  - Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including
      autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance.
      Recently, arRP has been associated with mutations in EYS (Eyes shut homolog),
      which is a major causative gene for this disease. This study was conducted to
      determine the spectrum and frequency of EYS mutations in 100 Japanese arRP
      patients. To determine the prevalence of EYS mutations, all EYS exons were
      screened for mutations by polymerase chain reaction amplification, and sequence
      analysis was performed. We detected 67 sequence alterations in EYS, of which 21
      were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible
      pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations.
      The minimum observed prevalence of distinct EYS mutations in our study was 18%
      (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the
      remaining 9 with only one such mutation). Among these mutations, 2 novel
      truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X),
      were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the
      mutated alleles. Although these 2 truncating mutations were not detected in
      Japanese patients with adRP or Leber's congenital amaurosis, we detected them in
      Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA
      mutation was more frequently detected than the c.8868C>A mutation. The 18%
      estimated prevalence of very likely pathogenic mutations in our study suggests a
      major involvement of EYS in the pathogenesis of arRP in the Japanese population.
      Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very
      likely and possible pathogenic mutations, was largely different from the
      previously reported spectrum in patients from non-Asian populations. Screening
      for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very
      effective for the genetic testing and counseling of RP patients in Japan.

PMID- 22363544
TI  - Pneumococcal antibody concentrations and carriage of pneumococci more than 3
      years after infant immunization with a pneumococcal conjugate vaccine.
AB  - BACKGROUND: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose
      schedule, protected Gambian children against pneumococcal disease and reduced
      nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the
      effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7)
      on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary
      vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a subsample of children
      who had received 3 doses of either PCV-9 or placebo (controls) into this follow
      up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9
      serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined
      before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a
      median age of 45 months (range, 38-52 months); 138 had received 3 doses of PCV-9
      in infancy and 144 were controls. Before receiving PCV-7, a high proportion of
      children had antibody concentrations >0.35 ug/mL to most of the serotypes in PCV
      9 (average of 75% in the PCV-9 and 66% in the control group respectively). The
      geometric mean antibody concentrations in the vaccinated group were significantly
      higher compared to controls for serotypes 6B, 14, and 23F. Antibody
      concentrations were significantly increased to serotypes in the PCV-7 vaccine
      both 6-8 weeks and 16-18 months after PCV-7. Antibodies to serotypes 6B, 9V and
      23F were higher in the PCV-9 group than in the control group 6-8 weeks after PCV
      7, but only the 6B difference was sustained at 16-18 months. There was no
      significant difference in nasopharyngeal carriage between the two groups.
      CONCLUSIONS/SIGNIFICANCE: Pneumococcal antibody concentrations in Gambian
      children were high 34-48 months after a 3-dose primary infant vaccination series
      of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly
      higher than in control children for 3 of the 9 serotypes. Antibody concentrations
      increased after PCV-7 and remained raised for at least 18 months.

PMID- 22363545
TI  - Antimetastatic effects of norcantharidin on hepatocellular carcinoma by
      transcriptional inhibition of MMP-9 through modulation of NF-kB activity.
AB  - BACKGROUND: The rate of morbidity and mortality of hepatocellular carcinoma (HCC)
      in Taiwan has not lessened because of difficulty in treating tumor metastasis.
      Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma,
      breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological
      anticancer activities, including apoptosis. However, detailed effects and
      molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were
      subjected to treatment with NCTD and then analyzed to determine the effects of
      NCTD on cell metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Modified Boyden chamber
      assays revealed that NCTD treatment inhibited cell migration and invasion
      capacities of HCC cells substantially. Results of zymography and western blotting
      showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9)
      and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot
      analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA
      level, quantitative real-time PCR, and promoter assays evaluated the inhibitory
      effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin
      immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to
      these proteins was reactive to the transcription protein nuclear factor (NF)
      kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by
      western blot analysis, which revealed decreased nuclear-factor DNA-binding
      activity after NCTD treatment. CONCLUSIONS: NCTD inhibited MMP-9 and u-PA
      expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway
      which serves as a powerful chemopreventive agent in HCC cell metastasis.

PMID- 22363546
TI  - Activation of the AMP-activated protein kinase (AMPK) by nitrated lipids in
      endothelial cells.
AB  - The AMP-activated protein kinase (AMPK) is an important regulator of endothelial
      metabolic and functional homeostasis. Here, we examined the regulation of AMPK by
      nitrated oleic acid (OA-NO(2)) and investigated the implications in endothelial
      function. Treatment of bovine aortic endothelial cells (BAECs) with OA-NO(2)
      induced a significant increase in both AMPK-Thr172 phosphorylation and AMPK
      activity as well as upregulation of heme oxygenase (HO)-1 and hypoxia-inducible
      factor (HIF)-1alpha. Pharmacologic inhibition or genetic ablation of HO-1 or HIF
      1alpha abolished OA-NO(2)-induced AMPK phosphorylation. OA-NO(2) induced a
      dramatic increase in extracellular signal-regulated kinase (ERK)1/2
      phosphorylation that was abrogated by the HO-1 inhibitor, zinc deuteroporphyrin
      IX 2,4-bis-ethylene glycol (ZnBG). Inhibition of ERK1/2 using UO126 or PD98059
      reduced but did not abolish OA-NO(2)-induced HIF-1alpha upregulation, suggesting
      that OA-NO(2)/HO-1-initiated HIF-1alpha induction is partially dependent on
      ERK1/2 activity. In addition, OA-NO(2) enhanced endothelial intracellular Ca(2+),
      an effect that was inhibited by the HIF-1alpha inhibitor, YC-1, and by HIF-1alpha
      siRNA. These results implicate the involvement of HIF-1alpha. Experiments using
      the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor STO-609,
      the selective CaMKII inhibitor KN-93, and an isoform-specific siRNA demonstrated
      that OA-NO(2)-induced AMPK phosphorylation was dependent on CaMKKbeta. Together,
      these results demonstrate that OA-NO(2) activates AMPK in endothelial cells via
      an HO-1-dependent mechanism that increases HIF-1alpha protein expression and
      Ca(2+)/CaMKKbeta activation.

PMID- 22363547
TI  - Square-cut: a segmentation algorithm on the basis of a rectangle shape.
AB  - We present a rectangle-based segmentation algorithm that sets up a graph and
      performs a graph cut to separate an object from the background. However, graph
      based algorithms distribute the graph's nodes uniformly and equidistantly on the
      image. Then, a smoothness term is added to force the cut to prefer a particular
      shape. This strategy does not allow the cut to prefer a certain structure,
      especially when areas of the object are indistinguishable from the background. We
      solve this problem by referring to a rectangle shape of the object when sampling
      the graph nodes, i.e., the nodes are distributed non-uniformly and non
      equidistantly on the image. This strategy can be useful, when areas of the object
      are indistinguishable from the background. For evaluation, we focus on vertebrae
      images from Magnetic Resonance Imaging (MRI) datasets to support the time
      consuming manual slice-by-slice segmentation performed by physicians. The ground
      truth of the vertebrae boundaries were manually extracted by two clinical experts
      (neurological surgeons) with several years of experience in spine surgery and
      afterwards compared with the automatic segmentation results of the proposed
      scheme yielding an average Dice Similarity Coefficient (DSC) of 90.97+/-2.2%.

PMID- 22363548
TI  - Integrin beta3 crosstalk with VEGFR accommodating tyrosine phosphorylation as a
      regulatory switch.
AB  - Integrins mediate cell adhesion, migration, and survival by connecting
      intracellular machinery with the surrounding extracellular matrix. Previous
      studies demonstrated the importance of the interaction between beta(3) integrin
      and VEGF type 2 receptor (VEGFR2) in VEGF-induced angiogenesis. Here we present
      in vitro evidence of the direct association between the cytoplasmic tails (CTs)
      of beta(3) and VEGFR2. Specifically, the membrane-proximal motif around (801)YLSI
      in VEGFR2 mediates its binding to non-phosphorylated beta(3)CT, accommodating an
      alpha-helical turn in integrin bound conformation. We also show that Y(747)
      phosphorylation of beta(3) enhances the above interaction. To demonstrate the
      importance of beta(3) phosphorylation in endothelial cell functions, we
      synthesized beta(3)CT-mimicking Y(747) phosphorylated and unphosphorylated
      membrane permeable peptides. We show that a peptide containing phospho-Y(747) but
      not F(747) significantly inhibits VEGF-induced signaling and angiogenesis.
      Moreover, phospho-Y(747) peptide exhibits inhibitory effect only in WT but not in
      beta(3) integrin knock-out or beta(3) integrin knock-in cells expressing beta(3)
      with two tyrosines substituted for phenylalanines, demonstrating its specificity.
      Importantly, these peptides have no effect on fibroblast growth factor receptor
      signaling. Collectively these data provide novel mechanistic insights into
      phosphorylation dependent cross-talk between integrin and VEGFR2.

PMID- 22363549
TI  - The effect of sensory uncertainty due to amblyopia (lazy eye) on the planning and
      execution of visually-guided 3D reaching movements.
AB  - BACKGROUND: Impairment of spatiotemporal visual processing in amblyopia has been
      studied extensively, but its effects on visuomotor tasks have rarely been
      examined. Here, we investigate how visual deficits in amblyopia affect motor
      planning and online control of visually-guided, unconstrained reaching movements.
      METHODS: Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13
      visually-normal participants were recruited. Participants reached and touched a
      visual target during binocular and monocular viewing. Motor planning was assessed
      by examining spatial variability of the trajectory at 50-100 ms after movement
      onset. Online control was assessed by examining the endpoint variability and by
      calculating the coefficient of determination (R(2)) which correlates the spatial
      position of the limb during the movement to endpoint position. RESULTS: Patients
      with amblyopia had reduced precision of the motor plan in all viewing conditions
      as evidenced by increased variability of the reach early in the trajectory.
      Endpoint precision was comparable between patients with mild amblyopia and
      control participants. Patients with severe amblyopia had reduced endpoint
      precision along azimuth and elevation during amblyopic eye viewing only, and
      along the depth axis in all viewing conditions. In addition, they had
      significantly higher R(2) values at 70% of movement time along the elevation and
      depth axes during amblyopic eye viewing. CONCLUSION: Sensory uncertainty due to
      amblyopia leads to reduced precision of the motor plan. The ability to implement
      online corrections depends on the severity of the visual deficit, viewing
      condition, and the axis of the reaching movement. Patients with mild amblyopia
      used online control effectively to compensate for the reduced precision of the
      motor plan. In contrast, patients with severe amblyopia were not able to use
      online control as effectively to amend the limb trajectory especially along the
      depth axis, which could be due to their abnormal stereopsis.

PMID- 22363550
TI  - Gender differences in immune reconstitution: a multicentric cohort analysis in
      sub-Saharan Africa.
AB  - BACKGROUND: In sub-Saharan Africa, men living with HIV often start ART at more
      advanced stages of disease and have higher early mortality than women. We
      investigated gender difference in long-term immune reconstitution.
      METHODS/PRINCIPAL FINDINGS: Antiretroviral-naive adults who received ART for at
      least 9 months in four HIV programs in sub-Saharan Africa were included.
      Multivariate mixed linear models were used to examine gender differences in
      immune reconstitution on first line ART. A total of 21,708 patients (68% women)
      contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART
      were 149 [IQR 85-206] for women and 125 cells/uL [IQR 63-187] for men. After the
      first year on ART, immune recovery was higher in women than in men, and gender
      based differences increased by 20 CD4 cells/uL per year on average (95% CI 16-23;
      P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels
      experienced similar gains compared to patients with high initial levels,
      including those with CD4>250 cells/uL (difference between patients with <50
      cells/uL and those with >250 was 284 cells/uL; 95% CI 272-296; LR test for
      interaction with time p = 0.63). Among patients with initial CD4 count of 150-200
      cells/uL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4-2.5) and
      men after 4.5 years (95% CI 4.1-4.8) of ART use. CONCLUSION: Women achieved
      better long-term immune response to ART, reaching CD4 level associated with lower
      risks of AIDS related morbidity and mortality quicker than men.

PMID- 22363551
TI  - Healthy growth in children with Down syndrome.
AB  - OBJECTIVE: To provide cross-sectional height and head circumference (HC)
      references for healthy Dutch children with Down syndrome (DS), while considering
      the influence of concomitant disorders on their growth, and to compare growth
      between children with DS and children from the general population. STUDY DESIGN:
      Longitudinal growth and medical data were retrospectively collected from medical
      records in 25 of the 30 regional hospital-based outpatient clinics for children
      with DS in The Netherlands. Children with Trisomy 21 karyotype of Dutch descent
      born after 1982 were included. The LMS method was applied to fit growth
      references. RESULTS: We enrolled 1,596 children, and collected 10,558
      measurements for height and 1,778 for HC. Children with DS without concomitant
      disorders (otherwise healthy children) and those suffering only from mild
      congenital heart defects showed similar growth patterns. The established growth
      charts, based on all measurements of these two groups, demonstrate the three age
      periods when height differences between children with and without DS increase:
      during pregnancy, during the first three years of life, and during puberty. This
      growth pattern results in a mean final height of 163.4 cm in boys and 151.8 cm in
      girls (-2.9 standard deviation (SD) and -3.0 SD on general Dutch charts,
      respectively). Mean HC (0 to 15 months) was 2 SD less than in the general Dutch
      population. The charts are available at www.tno.nl/growth. CONCLUSIONS: Height
      and HC references showed that growth retardation in otherwise healthy children
      with DS meanly occurs in three critical periods of growth, resulting in shorter
      final stature and smaller HC than the general Dutch population shows. With these
      references, health care professionals can optimize their preventive care:
      monitoring growth of individual children with DS optimal, so that growth
      retarding comorbidities can be identified early, and focusing on the critical age
      periods to establish ways to optimize growth.

PMID- 22363552
TI  - Genome-wide analysis of the complex transcriptional networks of rice developing
      seeds.
AB  - BACKGROUND: The development of rice (Oryza sativa) seed is closely associated
      with assimilates storage and plant yield, and is fine controlled by complex
      regulatory networks. Exhaustive transcriptome analysis of developing rice embryo
      and endosperm will help to characterize the genes possibly involved in the
      regulation of seed development and provide clues of yield and quality
      improvement. PRINCIPAL FINDINGS: Our analysis showed that genes involved in
      metabolism regulation, hormone response and cellular organization processes are
      predominantly expressed during rice development. Interestingly, 191 transcription
      factor (TF)-encoding genes are predominantly expressed in seed and 59 TFs are
      regulated during seed development, some of which are homologs of seed-specific
      TFs or regulators of Arabidopsis seed development. Gene co-expression network
      analysis showed these TFs associated with multiple cellular and metabolism
      pathways, indicating a complex regulation of rice seed development. Further, by
      employing a cold-resistant cultivar Hanfeng (HF), genome-wide analyses of seed
      transcriptome at normal and low temperature reveal that rice seed is sensitive to
      low temperature at early stage and many genes associated with seed development
      are down-regulated by low temperature, indicating that the delayed development of
      rice seed by low temperature is mainly caused by the inhibition of the
      development-related genes. The transcriptional response of seed and seedling to
      low temperature is different, and the differential expressions of genes in
      signaling and metabolism pathways may contribute to the chilling tolerance of HF
      during seed development. CONCLUSIONS: These results provide informative clues and
      will significantly improve the understanding of rice seed development regulation
      and the mechanism of cold response in rice seed.

PMID- 22363553
TI  - Physician and patient predictors of evidence-based prescribing in heart failure:
      a multilevel study.
AB  - BACKGROUND: The management of patients with heart failure (HF) needs to account
      for changeable and complex individual clinical characteristics. The use of renin
      angiotensin system inhibitors (RAAS-I) to target doses is recommended by
      guidelines. But physicians seemingly do not sufficiently follow this
      recommendation, while little is known about the physician and patient predictors
      of adherence. METHODS: To examine the coherence of primary care (PC) physicians'
      knowledge and self-perceived competencies regarding RAAS-I with their respective
      prescribing behavior being related to patient-associated barriers. Cross
      sectional follow-up study after a randomized medical educational intervention
      trial with a seven month observation period. PC physicians (n = 37) and patients
      with systolic HF (n = 168) from practices in Baden-Wuerttemberg. Measurements
      were knowledge (blueprint-based multiple choice test), self-perceived
      competencies (questionnaire on global confidence in the therapy and on frequency
      of use of RAAS-I), and patient variables (age, gender, NYHA functional status,
      blood pressure, potassium level, renal function). Prescribing was collected from
      the trials' documentation. The target variable consisted of >=50% of recommended
      RAAS-I dosage being investigated by two-level logistic regression models.
      RESULTS: Patients (69% male, mean age 68.8 years) showed symptomatic and
      objectified left ventricular (NYHA II vs. III/IV: 51% vs. 49% and mean LVEF
      33.3%) and renal (GFR<50%: 22%) impairment. Mean percentage of RAAS-I target dose
      was 47%, 59% of patients receiving >=50%. Determinants of improved prescribing of
      RAAS-I were patient age (OR 0.95, CI 0.92-0.99, p = 0.01), physician's global
      self-confidence at follow-up (OR 1.09, CI 1.02-1.05, p = 0.01) and NYHA class (II
      vs. III/IV) (OR 0.63, CI 0.38-1.05, p = 0.08). CONCLUSIONS: A change in
      physician's confidence as a predictor of RAAS-I dose increase is a new finding
      that might reflect an intervention effect of improved physicians' intention and
      that might foster novel strategies to improve safe evidence-based prescribing.
      These should include targeting knowledge, attitudes and skills.

PMID- 22363554
TI  - Cortical gyrification and sulcal spans in early stage Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by an insidious onset of progressive
      cerebral atrophy and cognitive decline. Previous research suggests that cortical
      folding and sulcal width are associated with cognitive function in elderly
      individuals, and the aim of the present study was to investigate these
      morphological measures in patients with AD. The sample contained 161
      participants, comprising 80 normal controls, 57 patients with very mild AD, and
      24 patients with mild AD. From 3D T1-weighted brain scans, automated methods were
      used to calculate an index of global cortex gyrification and the width of five
      individual sulci: superior frontal, intra-parietal, superior temporal, central,
      and Sylvian fissure. We found that global cortex gyrification decreased with
      increasing severity of AD, and that the width of all individual sulci
      investigated other than the intra-parietal sulcus was greater in patients with
      mild AD than in controls. We also found that cognitive functioning, as assessed
      by Mini-Mental State Examination (MMSE) scores, decreased as global cortex
      gyrification decreased. MMSE scores also decreased in association with a widening
      of all individual sulci investigated other than the intra-parietal sulcus. The
      results suggest that abnormalities of global cortex gyrification and regional
      sulcal span are characteristic of patients with even very mild AD, and could thus
      facilitate the early diagnosis of this condition.

PMID- 22363555
TI  - Two component systems: physiological effect of a third component.
AB  - Signal transduction systems mediate the response and adaptation of organisms to
      environmental changes. In prokaryotes, this signal transduction is often done
      through Two Component Systems (TCS). These TCS are phosphotransfer protein
      cascades, and in their prototypical form they are composed by a kinase that
      senses the environmental signals (SK) and by a response regulator (RR) that
      regulates the cellular response. This basic motif can be modified by the addition
      of a third protein that interacts either with the SK or the RR in a way that
      could change the dynamic response of the TCS module. In this work we aim at
      understanding the effect of such an additional protein (which we call "third
      component") on the functional properties of a prototypical TCS. To do so we build
      mathematical models of TCS with alternative designs for their interaction with
      that third component. These mathematical models are analyzed in order to identify
      the differences in dynamic behavior inherent to each design, with respect to
      functionally relevant properties such as sensitivity to changes in either the
      parameter values or the molecular concentrations, temporal responsiveness,
      possibility of multiple steady states, or stochastic fluctuations in the system.
      The differences are then correlated to the physiological requirements that
      impinge on the functioning of the TCS. This analysis sheds light on both, the
      dynamic behavior of synthetically designed TCS, and the conditions under which
      natural selection might favor each of the designs. We find that a third component
      that modulates SK activity increases the parameter space where a bistable
      response of the TCS module to signals is possible, if SK is monofunctional, but
      decreases it when the SK is bifunctional. The presence of a third component that
      modulates RR activity decreases the parameter space where a bistable response of
      the TCS module to signals is possible.

PMID- 22363556
TI  - A randomly-controlled study on the cardiac function at the early stage of return
      to the plains after short-term exposure to high altitude.
AB  - High altitude acclimatization and adaptation mechanisms have been well clarified,
      however, high altitude de-adaptation mechanism remains unclear. In this study, we
      conducted a controlled study on cardiac functions in 96 healthy young male who
      rapidly entered the high altitude (3700 m) and returned to the plains (1500 m)
      after 50 days. Ninety eight healthy male who remained at low altitude were
      recruited as control group. The mean pulmonary arterial pressure (mPAP), left
      ventricular ejection fraction (LVEF), left ventricular fraction shortening
      (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine
      kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin
      1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1alpha (HIF
      1alpha), 8-iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), superoxide dismutase
      (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m
      respectively. The results showed that after short-term exposure to high altitude
      mPAP and Tei index increased significantly, while LVEF and LVFS decreased
      significantly. These changes were positively correlated with altitude. On the
      15(th) day after the subjects returned to low altitude, mPAP, LVEF and LVFS
      levels returned to the same level as those of the control subjects, but the Tei
      index in the returned subjects was still significantly higher than that in the
      control subjects (P<0.01). We also found that changes in Tei index was positively
      correlated with mPAP, ET-1, HIF-1alpha and 8-iso PGF(2alpha) levels, and
      negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These
      findings suggest that cardiac function de-adapts when returning to the plains
      after short-term exposure to high altitude and the function recovery takes a
      relatively long time.

PMID- 22363557
TI  - Bloodmeal analysis reveals avian Plasmodium infections and broad host preferences
      of Culicoides (Diptera: Ceratopogonidae) vectors.
AB  - Changing environmental conditions and human encroachment on natural habitats
      bring human populations closer to novel sources of parasites, which might then
      develop into new emerging diseases. Diseases transmitted by host generalist
      vectors are of special interest due to their capacity to move pathogens into
      novel hosts. We hypothesize that humans using forests for recreation are exposed
      to a broad range of parasites from wild animals and their vectors. A corollary of
      this is that new vector-host, parasite-host, and vector-parasite associations
      could eventually develop. Thus, we expect to observe atypical vector-host
      associations. Using molecular bloodmeal analysis via amplification of the mtDNA
      COI gene we identified the vertebrate hosts of Culicoides (Diptera:
      Ceratopogonidae) species in a sub-urban forest of Southwestern Germany.
      Bloodmeals were also checked for haemosporidian infections by amplifying a
      fragment of the mtDNA cyt b gene. We identified a total of 20 Culicoides species,
      thirteen of which fed on humans. From 105 screened bloodmeals we obtained high
      quality sequences for 77 samples, 73 (94.8%) originated from humans, two from
      livestock (Bos taurus and Equus caballus), and two from wild birds (Sylvia
      atricapilla and Turdus merula). We found that four Culicoides species previously
      assumed to feed exclusively on either birds (C. kibunensis) or domestic mammals
      (C. chiopterus, C. deltus, C. scoticus) fed also on humans. A total of six
      Culicoides abdomens were infected with avian haemosporidian parasites (Plasmodium
      or Haemoproteus), four of those abdomens contained blood derived from humans. Our
      results suggest that parasites of wild animals may be transferred to humans
      through infectious bites of Culicoides vectors. Further, we show that Culicoides
      vectors believed to be a specialist on specific vertebrate groups can have
      plastic feeding preferences, and that Culicoides are susceptible to infection by
      Plasmodium parasites, though vector viability must still be experimentally
      demonstrated.

PMID- 22363558
TI  - Asymptomatic carriage of plasmodium in urban Dakar: the risk of malaria should
      not be underestimated.
AB  - INTRODUCTION: The objective of this study was to measure the rate of asymptomatic
      carriage of plasmodium in the Dakar region two years after the implementation of
      new strategies in clinical malaria management. METHODOLOGY: Between October and
      December 2008, 2952 households selected in 50 sites of Dakar area, were visited
      for interviews and blood sampling. Giemsa-stained thick blood smears (TBS) were
      performed for microscopy in asymptomatic adult women and children aged 2 to 10
      years. To ensure the quality of the microscopy, we performed a polymerase chain
      reaction (PCR) with real time qPCR in all positive TBS by microscopy and in a
      sample of negative TBS and filter paper blood spots. RESULTS: The analysis has
      concerned 2427 women and 2231 children. The mean age of the women was 35.6 years.
      The mean age of the children was 5.4 years. The parasite prevalence was 2.01%
      (49/2427) in women and 2.15% (48/2231) in children. Parasite prevalence varied
      from one study site to another, ranging from 0 to 7.41%. In multivariate
      analysis, reporting a malaria episode in 2008 was associated with plasmodium
      carriage (OR = 2.57, P = 0.002) in women; in children, a malaria episode (OR =
      6.19, P<0.001) and a travel out of Dakar during last 3 months (OR = 2.27, P =
      0.023) were associated with plasmodium carriage. Among the positive TBS, 95.8%
      (93/97) were positive by plasmodium PCR. Among the negative TBS, 13.9% (41/293)
      were positive by PCR. In blood spots, 15.2% (76/500) were positive by PCR. We
      estimated at 16.5% the parasite prevalence if PCR were performed in 4658 TBS.
      CONCLUSION: Parasite prevalence in Dakar area seemed to be higher than the rate
      found by microscopy. PCR may be the best tool for measuring plasmodium prevalence
      in the context of low transmission. Environmental conditions play a major role in
      the heterogeneity of parasite prevalence within sites.

PMID- 22363559
TI  - Modeling activity and target-dependent developmental cell death of mouse retinal
      ganglion cells ex vivo.
AB  - Programmed cell death is widespread during the development of the central nervous
      system and serves multiple purposes including the establishment of neural
      connections. In the mouse retina a substantial reduction of retinal ganglion
      cells (RGCs) occurs during the first postnatal week, coinciding with the
      formation of retinotopic maps in the superior colliculus (SC). We previously
      established a retino-collicular culture preparation which recapitulates the
      progressive topographic ordering of RGC projections during early post-natal life.
      Here, we questioned whether this model could also be suitable to examine the
      mechanisms underlying developmental cell death of RGCs. Brn3a was used as a
      marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled
      neurons was found in the retinal explant with a timing that paralleled that
      observed in vivo. In contrast, the density of photoreceptors or of starburst
      amacrine cells increased, mimicking the evolution of these cell populations in
      vivo. Blockade of neural activity with tetrodotoxin increased the number of
      surviving Brn3a-labelled neurons in the retinal explant, as did the increase in
      target availability when one retinal explant was confronted with 2 or 4
      collicular slices. Thus, this ex vivo model reproduces the developmental
      reduction of RGCs and recapitulates its regulation by neural activity and target
      availability. It therefore offers a simple way to analyze developmental cell
      death in this classic system. Using this model, we show that ephrin-A signaling
      does not participate to the regulation of the Brn3a population size in the
      retina, indicating that eprhin-A-mediated elimination of exuberant projections
      does not involve developmental cell death.

PMID- 22363560
TI  - Discovery of prostamide F2alpha and its role in inflammatory pain and dorsal horn
      nociceptive neuron hyperexcitability.
AB  - It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2
      in the spinal cord of rats with kaolin/lambda-carrageenan-induced knee
      inflammation, and that this mechanism contributes to the analgesic effects of COX
      2 inhibitors in this experimental model. We report the development of a specific
      method for the identification of endocannabinoid COX-2 metabolites, its
      application to measure the levels of these compounds in tissues, and the finding
      of prostamide F(2alpha) (PMF(2alpha)) in mice with knee inflammation. Whereas the
      levels of spinal endocannabinoids were not significantly altered by kaolin/lambda
      carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA,
      PMF(2alpha), were strongly elevated. The formation of PMF(2alpha) was reduced by
      indomethacin (a non-selective COX inhibitor), NS-398 (a selective COX-2
      inhibitor) and SC-560 (a selective COX-1 inhibitor). In healthy mice, spinal
      application of PMF(2alpha) increased the firing of nociceptive (NS) neurons, and
      correspondingly reduced the threshold of paw withdrawal latency (PWL). These
      effects were attenuated by the PMF(2alpha) receptor antagonist AGN211336, but not
      by the FP receptor antagonist AL8810. Also prostaglandin F(2alpha) increased NS
      neuron firing and reduced the threshold of PWL in healthy mice, and these effects
      were antagonized by AL8810, and not by AGN211336. In mice with kaolin/lambda
      carrageenan-induced knee inflammation, AGN211336, but not AL8810, reduced the
      inflammation-induced NS neuron firing and reduction of PWL. These findings
      suggest that inflammation-induced, and prostanoid-mediated, enhancement of dorsal
      horn NS neuron firing stimulates the production of spinal PMF(2alpha), which in
      turn contributes to further NS neuron firing and pain transmission by activating
      specific receptors.

PMID- 22363561
TI  - Effect of Lactobacillus salivarius bacteriocin Abp118 on the mouse and pig
      intestinal microbiota.
AB  - Lactobacilli are gram-positive bacteria that are a subdominant element in the
      human gastrointestinal microbiota, and which are commonly used in the food
      industry. Some lactobacilli are considered probiotic, and have been associated
      with health benefits. However, there is very little culture-independent
      information on how consumed probiotic microorganisms might affect the entire
      intestinal microbiota. We therefore studied the impact of the administration of
      Lactobacillus salivarius UCC118, a microorganism well characterized for its
      probiotic properties, on the composition of the intestinal microbiota in two
      model animals. UCC118 has anti-infective activity due to production of the
      bacteriocin Abp118, a broad-spectrum class IIb bacteriocin, which we hypothesized
      could impact the microbiota. Mice and pigs were administered wild-type (WT) L.
      salivarius UCC118 cells, or a mutant lacking bacteriocin production. The
      microbiota composition was determined by pyrosequencing of 16S rRNA gene
      amplicons from faeces. The data show that L. salivarius UCC118 administration had
      no significant effect on proportions of major phyla comprising the mouse
      microbiota, whether the strain was producing bacteriocin or not. However, L.
      salivarius UCC118 WT administration led to a significant decrease in Spirochaetes
      levels, the third major phylum in the untreated pig microbiota. In both pigs and
      mice, L. salivarius UCC118 administration had an effect on Firmicutes genus
      members. This effect was not observed when the mutant strain was administered,
      and was thus associated with bacteriocin production. Surprisingly, in both
      models, L. salivarius UCC118 administration and production of Abp118 had an
      effect on gram-negative microorganisms, even though Abp118 is normally not active
      in vitro against this group of microorganisms. Thus L. salivarius UCC118
      administration has a significant but subtle impact on mouse and pig microbiota,
      by a mechanism that seems at least partially bacteriocin-dependent.

PMID- 22363562
TI  - Evolutionary dynamics of the Pgk1 gene in the polyploid genus Kengyilia
      (Triticeae: Poaceae) and its diploid relatives.
AB  - The level and pattern of nucleotide variation in duplicate gene provide important
      information on the evolutionary history of polyploids and divergent process
      between homoeologous loci within lineages. Kengyilia is a group of allohexaploid
      species with the StYP genomic constitutions in the wheat tribe. To investigate
      the evolutionary dynamics of the Pgk1 gene in Kengyilia and its diploid
      relatives, three copies of Pgk1 homoeologues were isolated from all sampled
      hexaploid Kengyilia species and analyzed with the Pgk1 sequences from 47 diploid
      taxa representing 18 basic genomes in Triticeae. Sequence diversity patterns and
      genealogical analysis suggested that (1) Kengyilia species from the Central Asia
      and the Qinghai-Tibetan plateau have independent origins with geographically
      differentiated P genome donors and diverged levels of nucleotide diversity at
      Pgk1 locus; (2) a relatively long-time sweep event has allowed the Pgk1 gene
      within Agropyron to adapt to cold climate triggered by the recent uplifts of the
      Qinghai-Tibetan Plateau; (3) sweep event and population expansion might result in
      the difference in the d(N)/d(S) value of the Pgk1 gene in allopatric Agropyron
      populations, and this difference may be genetically transmitted to Kengyilia
      lineages via independent polyploidization events; (4) an 83 bp MITE element
      insertion has shaped the Pgk1 loci in the P genome lineage with different
      geographical regions; (5) the St and P genomes in Kengyilia were donated by
      Pseudoroegneria and Agropyron, respectively, and the Y genome is closely related
      to the Xp genome of Peridictyon sanctum. The interplay of evolutionary forces
      involving diverged natural selection, population expansion, and transposable
      events in geographically differentiated P genome donors could attribute to
      geographical differentiation of Kengyilia species via independent origins.

PMID- 22363563
TI  - Paleogenetic analyses reveal unsuspected phylogenetic affinities between mice and
      the extinct Malpaisomys insularis, an endemic rodent of the Canaries.
AB  - BACKGROUND: The lava mouse, Malpaisomys insularis, was endemic to the Eastern
      Canary islands and became extinct at the beginning of the 14(th) century when the
      Europeans reached the archipelago. Studies to determine Malpaisomys' phylogenetic
      affinities, based on morphological characters, remained inconclusive because
      morphological changes experienced by this insular rodent make phylogenetic
      investigations a real challenge. Over 20 years since its first description,
      Malpaisomys' phylogenetic position remains enigmatic. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we resolved this issue using molecular characters.
      Mitochondrial and nuclear markers were successfully amplified from subfossils of
      three lava mouse samples. Molecular phylogenetic reconstructions revealed,
      without any ambiguity, unsuspected relationships between Malpaisomys and extant
      mice (genus Mus, Murinae). Moreover, through molecular dating we estimated the
      origin of the Malpaisomys/mouse clade at 6.9 Ma, corresponding to the maximal age
      at which the archipelago was colonised by the Malpaisomys ancestor via natural
      rafting. CONCLUSION/SIGNIFICANCE: This study reconsiders the derived
      morphological characters of Malpaisomys in light of this unexpected molecular
      finding. To reconcile molecular and morphological data, we propose to consider
      Malpaisomys insularis as an insular lineage of mouse.

PMID- 22363564
TI  - Highly sensitive detection of Staphylococcus aureus directly from patient blood.
AB  - BACKGROUND: Rapid detection of bloodstream infections (BSIs) can be lifesaving.
      We investigated the sample processing and assay parameters necessary for highly
      sensitive detection of bloodstream bacteria, using Staphylococcus aureus as a
      model pathogen and an automated fluidic sample processing-polymerase chain
      reaction (PCR) platform as a model diagnostic system. METHODOLOGY/PRINCIPAL
      FINDINGS: We compared a short 128 bp amplicon hemi-nested PCR and a relatively
      shorter 79 bp amplicon nested PCR targeting the S. aureus nuc and sodA genes,
      respectively. The sodA nested assay showed an enhanced limit of detection (LOD)
      of 5 genomic copies per reaction or 10 colony forming units (CFU) per ml blood
      over 50 copies per reaction or 50 CFU/ml for the nuc assay. To establish optimal
      extraction protocols, we investigated the relative abundance of the bacteria in
      different components of the blood (white blood cells (WBCs), plasma or whole
      blood), using the above assays. The blood samples were obtained from the patients
      who were culture positive for S. aureus. Whole blood resulted in maximum PCR
      positives with sodA assay (90% positive) as opposed to cell-associated bacteria
      (in WBCs) (71% samples positive) or free bacterial DNA in plasma (62.5% samples
      positive). Both the assays were further tested for direct detection of S. aureus
      in patient whole blood samples that were contemporaneous culture positive. S.
      aureus was detected in 40/45 of culture-positive patients (sensitivity 89%, 95%
      CI 0.75-0.96) and 0/59 negative controls with the sodA assay (specificity 100%,
      95% CI 0.92-1). CONCLUSIONS: We have demonstrated a highly sensitive two-hour
      assay for detection of sepsis causing bacteria like S. aureus directly in 1 ml of
      whole blood, without the need for blood culture.

PMID- 22363565
TI  - Marine invasion in the Mediterranean Sea: the role of abiotic factors when there
      is no biological resistance.
AB  - The tropical red alga Womersleyella setacea (Rhodomelaceae, Rhodophyta) is
      causing increasing concern in the Mediterranean Sea because of its invasive
      behavior. After its introduction it has colonized most Mediterranean areas, but
      the mechanism underlying its acclimatization and invasion process remains
      unknown. To understand this process, we decided i) to assess in situ the seasonal
      biomass and phenological patterns of populations inhabiting the Mediterranean Sea
      in relation to the main environmental factors, and ii) to experimentally
      determine if the tolerance of W. setacea to different light and temperature
      conditions can explain its colonization success, as well as its bathymetric
      distribution range. The bathymetric distribution, biomass, and phenology of W.
      setacea were studied at two localities, and related to irradiance and temperature
      values recorded in situ. Laboratory experiments were set up to study survival,
      growth and reproduction under contrasting light and temperature conditions in the
      short, mid, and long term. Results showed that, in the studied area, the
      bathymetric distribution of W. setacea is restricted to a depth belt between 25
      and 40 m deep, reaching maximum biomass values (126 g dw m(-2)) at 30 m depth. In
      concordance, although in the short term W. setacea survived and grew in a large
      range of environmental conditions, its life requirements for the mid and long
      term were dim light levels and low temperatures. Biomass of Womersleyella setacea
      did not show any clear seasonal pattern, though minimum values were reported in
      spring. Reproductive structures were always absent. Bearing in mind that no
      herbivores feed on Womersleyella setacea and that its thermal preferences are
      more characteristic of temperate than of tropical seaweeds, low light (50 umol
      photon m(-2) s(-1)) and low temperature (12 degrees C) levels are critical for W.
      setacea survival and growth, thus probably determining its spread and bathymetric
      distribution across the Mediterranean Sea.

PMID- 22363566
TI  - MRI of auto-transplantation of bone marrow-derived stem-progenitor cells for
      potential repair of injured arteries.
AB  - BACKGROUND: This study was to validate the feasibility of using clinical 3.0T MRI
      to monitor the migration of autotransplanted bone marrow (BM)-derived stem
      progenitor cells (SPC) to the injured arteries of near-human sized swine for
      potential cell-based arterial repair. METHODOLOGY: The study was divided into two
      phases. For in vitro evaluation, BM cells were extracted from the iliac crests of
      13 domestic pigs and then labeled with a T2 contrast agent, Feridex, and/or a
      fluorescent tissue marker, PKH26. The viability, the proliferation efficiency and
      the efficacies of Feridex and/or PKH26 labeling were determined. For in vivo
      validation, the 13 pigs underwent endovascular balloon-mediated intimal damages
      of the iliofemoral arteries. The labeled or un-labeled BM cells were
      autotransplanted back to the same pig from which the BM cells were extracted.
      Approximately three weeks post-cell transplantation, 3.0T T2-weighted MRI was
      performed to detect Feridex-created signal voids of the transplanted BM cells in
      the injured iliofemoral arteries, which was confirmed by subsequent histologic
      correlation. PRINCIPAL FINDINGS: Of the in vitro study, the viability of dual
      labeled BM cells was 95-98%. The proliferation efficiencies of dual-labeled BM
      cells were not significantly different compared to those of non-labeled cells.
      The efficacies of Feridex- and PKH26 labeling were 90% and 100%, respectively. Of
      the in vivo study, 3.0T MRI detected the auto-transplanted BM cells migrated to
      the injured arteries, which was confirmed by histologic examinations. CONCLUSION:
      This study demonstrates the capability of using clinical 3.0T MRI to monitor the
      auto-transplantation of BM cells that migrate to the injured arteries of large
      animals, which may provide a useful MRI technique to monitor cell-based arterial
      repair.

PMID- 22363567
TI  - Brainstem respiratory oscillators develop independently of neuronal migration
      defects in the Wnt/PCP mouse mutant looptail.
AB  - The proper development and maturation of neuronal circuits require precise
      migration of component neurons from their birthplace (germinal zone) to their
      final positions. Little is known about the effects of aberrant neuronal position
      on the functioning of organized neuronal groups, especially in mammals. Here, we
      investigated the formation and properties of brainstem respiratory neurons in
      looptail (Lp) mutant mice in which facial motor neurons closely apposed to some
      respiratory neurons fail to migrate due to loss of function of the Wnt/Planar
      Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on
      embryonic hindbrain preparations, we found that respiratory neurons constituting
      the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the
      medulla in Vangl2(Lp/+) and Vangl2(Lp/Lp) embryos despite the failure of
      tangential migration of its normally adjacent facial motor nucleus. Anatomically,
      the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially
      Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator
      exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos.
      Furthermore, using hindbrain slices, we found that the other respiratory
      oscillator, the preBotzinger complex, was also anatomically and functionally
      established in Lp mutants. Importantly, the displaced e-pF oscillator established
      functional connections with the preBotC oscillator in Lp/+ mutants. Our data
      highlight the robustness of the developmental processes that assemble the
      neuronal networks mediating an essential physiological function.

PMID- 22363568
TI  - Microbial pattern recognition causes distinct functional micro-RNA signatures in
      primary human monocytes.
AB  - Micro-RNAs (miRNAs) are short, non-coding RNAs that regulate gene expression post
      transcriptionally. Several studies have demonstrated the relevance of miRNAs for
      a wide range of cellular mechanisms, however, the current knowledge on how miRNAs
      respond to relevant external stimuli, e.g. in disease scenarios is very limited.
      To generate a descriptive picture of the miRNA network associated to inflammatory
      responses, we quantified the levels of 330 miRNAs upon stimulation with a panel
      of pro-inflammatory components such as microbial pattern molecules (flagellin,
      diacylated lipopeptide lipopolysaccharide, muramyl dipeptide), infection with
      Listeria monocytogenes and TNF-alpha as pro-inflammatory control in primary human
      monocytes using real time PCR. As a result, we found distinct miRNA response
      clusters for each stimulus used. Additionally, we identified potential target
      genes of three selected miRNAs miR-129-5p, miR-146a and miR-378 which were part
      of PAMP-specific response clusters by transfecting THP1 monocytes with the
      corresponding pre- or anti-miRNAs and microfluidic PCR arrays. The miRNAs induced
      distinct transcriptomal signatures, e.g. overexpression of miRNA129-5p, which was
      selectively upregulated by the NOD2-elicitor MDP, led to an upregulation of
      DEFB1, IRAK1, FBXW7 and IKK gamma (Nemo). Our findings on highly co-regulated
      clusters of miRNAs support the hypothesis that miRNAs act in functional groups.
      This study indicates that miRNAs play an important role in fine-tuning
      inflammatory mechanisms. Further investigation in the field of miRNA responses
      will help to understand their effects on gene expression and may close the
      regulatory gap between mRNA and protein expression in inflammatory diseases.

PMID- 22363569
TI  - Therapeutic effects of liposome-enveloped Ligusticum chuanxiong essential oil on
      hypertrophic scars in the rabbit ear model.
AB  - Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts,
      results from an overproduction of fibroblasts and excessive deposition of
      collagen. Although treatment with surgical excision or steroid hormones can
      modify the symptoms, numerous treatment-related complications have been
      described. In view of this, we investigated the therapeutic effects of essential
      oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed
      hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal
      formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with
      hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily
      to the scars for 28 days. On postoperative day 56, the scar tissue was excised
      for masson's trichrome staining, detection of fibroblast apoptosis, assays of the
      levels of collagens I and III, and analysis of the mRNA expression of matrix
      metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor
      beta 1 (TGF-beta(1)). In addition, the scar elevation index (SEI) was also
      determined. As a result, LEO treatment significantly alleviated formed
      hypertrophic scars on rabbit ears. The levels of TGF-beta(1), MMP-1, collagen I,
      and collagen III were evidently decreased, and caspase -3 and -9 levels and
      apoptosis cells were markedly increased in the scar tissue. SEI was also
      significantly reduced. Histological findings exhibited significant amelioration
      of the collagen tissue. These results suggest that LEO possesses the favorable
      therapeutic effects on formed hypertrophic scars in the rabbit ear model and may
      be an effective cure for human hypertrophic scars.

PMID- 22363571
TI  - Establishment of motor neuron-V3 interneuron progenitor domain boundary in
      ventral spinal cord requires Groucho-mediated transcriptional corepression.
AB  - BACKGROUND: Dorsoventral patterning of the developing spinal cord is important
      for the correct generation of spinal neuronal types. This process relies in part
      on cross-repressive interactions between specific transcription factors whose
      expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of
      split (TLE) proteins are transcriptional corepressors suggested to be recruited
      by at least certain Sonic hedgehog-controlled transcription factors to mediate
      the formation of spatially distinct progenitor domains within the ventral spinal
      cord. The aim of this study was to characterize the involvement of TLE in
      mechanisms regulating the establishment of the boundary between the most ventral
      spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives
      rise to somatic motor neurons while the p3 domain generates V3 interneurons, we
      also examined the involvement of TLE in the acquisition of these neuronal fates.
      METHODOLOGY AND PRINCIPAL FINDINGS: A combination of in vivo loss- and gain-of
      function studies in the developing chick spinal cord was performed to
      characterize the role of TLE in ventral progenitor domain formation. It is shown
      here that TLE overexpression causes increased numbers of p3 progenitors and
      promotes the V3 interneuron fate while suppressing the motor neuron fate.
      Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors
      and postmitotic motor neurons. CONCLUSION: Based on these results, we propose
      that TLE is important to promote the formation of the p3 domain and subsequent
      generation of V3 interneurons.

PMID- 22363570
TI  - There's no place like home: crown-of-thorns outbreaks in the central pacific are
      regionally derived and independent events.
AB  - One of the most significant biological disturbances on a tropical coral reef is a
      population outbreak of the fecund, corallivorous crown-of-thorns sea star,
      Acanthaster planci. Although the factors that trigger an initial outbreak may
      vary, successive outbreaks within and across regions are assumed to spread via
      the planktonic larvae released from a primary outbreak. This secondary outbreak
      hypothesis is predominantly based on the high dispersal potential of A. planci
      and the assertion that outbreak populations (a rogue subset of the larger
      population) are genetically more similar to each other than they are to low
      density non-outbreak populations. Here we use molecular techniques to evaluate
      the spatial scale at which A. planci outbreaks can propagate via larval dispersal
      in the central Pacific Ocean by inferring the location and severity of gene flow
      restrictions from the analysis of mtDNA control region sequence (656 specimens,
      17 non-outbreak and six outbreak locations, six archipelagos, and three regions).
      Substantial regional, archipelagic, and subarchipelagic-scale genetic structuring
      of A. planci populations indicate that larvae rarely realize their dispersal
      potential and outbreaks in the central Pacific do not spread across the expanses
      of open ocean. On a finer scale, genetic partitioning was detected within two of
      three islands with multiple sampling sites. The finest spatial structure was
      detected at Pearl & Hermes Atoll, between the lagoon and forereef habitats (<10
      km). Despite using a genetic marker capable of revealing subtle partitioning, we
      found no evidence that outbreaks were a rogue genetic subset of a greater
      population. Overall, outbreaks that occur at similar times across population
      partitions are genetically independent and likely due to nutrient inputs and
      similar climatic and ecological conditions that conspire to fuel plankton blooms.

PMID- 22363573
TI  - Patients with asthma and comorbid allergic rhinitis: is optimal quality of life
      achievable in real life?
AB  - OBJECTIVES: Asthma trials suggest that patients reaching total disease control
      have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is
      present in almost 80% of asthmatics and impacts asthma control and patient HRQoL.
      We explored whether optimal HRQoL was reachable in a real-life setting, and
      evaluated the disease and patient related patterns associated to optimal HRQoL
      achievement. METHODS AND FINDINGS: Asthma and rhinitis HRQoL, illness perception,
      mood profiles, rhinitis symptoms and asthma control were assessed by means of
      validated tools in patients classified according to GINA and ARIA guidelines.
      Optimal HRQoL, identified by a Rhinasthma Global Summary (GS) score <=20 (score
      ranging from 0 to 100, where 100 represents the worst possible HRQoL), was
      reached by 78/209 (37.32%). With the exception of age, no associations were found
      between clinical and demographic characteristics and optimal HRQoL achievement.
      Patients reaching an optimal HRQoL differed in disease perception and mood
      compared to those not reaching an optimal HRQoL. Asthma control was significantly
      associated with optimal HRQoL (chi(2) = 49.599; p<0.001) and well-controlled and
      totally controlled patients significantly differed in achieving optimal HRQoL
      (chi(2) = 7.617; p<0.006). CONCLUSION: Approximately one third of the patients in
      our survey were found to have an optimal HRQoL. While unsatisfactory disease
      control was the primary reason why the remainder failed to attain optimal HRQoL,
      it is clear that illness perception and mood also played parts. Therefore,
      therapeutic plans should be directed not only toward achieving the best possible
      clinical control of asthma and comorbid rhinitis, but also to incorporating
      individualized elements according to patient-related characteristics.

PMID- 22363572
TI  - Pre-clinical evaluation of a replication-competent recombinant adenovirus
      serotype 4 vaccine expressing influenza H5 hemagglutinin.
AB  - BACKGROUND: Influenza virus remains a significant health and social concern in
      part because of newly emerging strains, such as avian H5N1 virus. We have
      developed a prototype H5N1 vaccine using a recombinant, replication-competent
      Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine
      strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza
      virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4
      H5-Vtn recombinant vector will be safe and induce protective immunity against
      H5N1 influenza virus infection and disease pathogenesis. METHODOLOGY/PRINCIPAL
      FINDINGS: The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3
      region of Ad4 to accommodate the influenza HA gene. Replication and growth
      kinetics of the vaccine virus in multiple human cell lines indicated that the
      vaccine virus is attenuated relative to the wild type virus. Expression of the HA
      transgene in infected cells was documented by flow cytometry, western blot
      analysis and induction of HA-specific antibody and cellular immune responses in
      mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine
      were protected against lethal H5N1 reassortant viral challenge even in the
      presence of pre-existing immunity to the Ad4 wild type virus.
      CONCLUSIONS/SIGNIFICANCE: Several non-clinical attributes of this vaccine
      including safety, induction of HA-specific humoral and cellular immunity, and
      efficacy were demonstrated using an animal model to support Phase 1 clinical
      trial evaluation of this new vaccine.

PMID- 22363574
TI  - Three-dimensional in vivo imaging of the murine liver: a micro-computed
      tomography-based anatomical study.
AB  - Various murine models are currently used to study acute and chronic pathological
      processes of the liver, and the efficacy of novel therapeutic regimens. The
      increasing availability of high-resolution small animal imaging modalities
      presents researchers with the opportunity to precisely identify and describe
      pathological processes of the liver. To meet the demands, the objective of this
      study was to provide a three-dimensional illustration of the macroscopic
      anatomical location of the murine liver lobes and hepatic vessels using small
      animal imaging modalities. We analysed micro-CT images of the murine liver by
      integrating additional information from the published literature to develop
      comprehensive illustrations of the macroscopic anatomical features of the murine
      liver and hepatic vasculature. As a result, we provide updated three-dimensional
      illustrations of the macroscopic anatomy of the murine liver and hepatic vessels
      using micro-CT. The information presented here provides researchers working in
      the field of experimental liver disease with a comprehensive, easily accessable
      overview of the macroscopic anatomy of the murine liver.

PMID- 22363575
TI  - Metallothionein (MT) -I and MT-II expression are induced and cause zinc
      sequestration in the liver after brain injury.
AB  - Experiments with transgenic over-expressing, and null mutant mice have determined
      that metallothionein-I and -II (MT-I/II) are protective after brain injury. MT
      I/II is primarily a zinc-binding protein and it is not known how it provides
      neuroprotection to the injured brain or where MT-I/II acts to have its effects.
      MT-I/II is often expressed in the liver under stressful conditions but to date,
      measurement of MT-I/II expression after brain injury has focused primarily on the
      injured brain itself. In the present study we measured MT-I/II expression in the
      liver of mice after cryolesion brain injury by quantitative reverse-transcriptase
      PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) with the UC1MT
      antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II(-/-))
      mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels
      were significantly increased within 24 hours of brain injury but hepatic MT-I/II
      protein levels were not significantly increased until 3 days post injury (DPI)
      and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc
      content was measured by atomic absorption spectroscopy and was found to decrease
      at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II(-/-)
      mice did not show a return to normal at 7 DPI which suggests that after brain
      injury, MT-I/II is responsible for sequestering elevated levels of zinc to the
      liver. CONCLUSION: MT-I/II is up-regulated in the liver after brain injury and
      modulates the amount of zinc that is sequestered to the liver.

PMID- 22363576
TI  - Tri-axial dynamic acceleration as a proxy for animal energy expenditure; should
      we be summing values or calculating the vector?
AB  - Dynamic body acceleration (DBA) has been used as a proxy for energy expenditure
      in logger-equipped animals, with researchers summing the acceleration (overall
      dynamic body acceleration--ODBA) from the three orthogonal axes of devices. The
      vector of the dynamic body acceleration (VeDBA) may be a better proxy so this
      study compared ODBA and VeDBA as proxies for rate of oxygen consumption using
      humans and 6 other species. Twenty-one humans on a treadmill ran at different
      speeds while equipped with two loggers, one in a straight orientation and the
      other skewed, while rate of oxygen consumption (VO2) was recorded. Similar data
      were obtained from animals but using only one (straight) logger. In humans, both
      ODBA and VeDBA were good proxies for VO2 with all r(2) values exceeding 0.88,
      although ODBA accounted for slightly but significantly more of the variation in
      VO2 than did VeDBA (P<0.03). There were no significant differences between ODBA
      and VeDBA in terms of the change in VO2 estimated by the acceleration data in a
      simulated situation of the logger being mounted straight but then becoming skewed
      (P = 0.744). In the animal study, ODBA and VeDBA were again good proxies for VO2
      with all r(2) values exceeding 0.70 although, again, ODBA accounted for slightly,
      but significantly, more of the variation in VO2 than did VeDBA (P<0.03). The
      simultaneous contraction of muscles, inserted variously for limb stability, may
      produce muscle oxygen use that at least partially equates with summing components
      to derive DBA. Thus, a vectorial summation to derive DBA cannot be assumed to be
      the more 'correct' calculation. However, although within the limitations of our
      simple study, ODBA appears a marginally better proxy for VO2. In the unusual
      situation where researchers are unable to guarantee at least reasonably
      consistent device orientation, they should use VeDBA as a proxy for VO2.

PMID- 22363578
TI  - A relative variation-based method to unraveling gene regulatory networks.
AB  - Gene regulatory network (GRN) reconstruction is essential in understanding the
      functioning and pathology of a biological system. Extensive models and algorithms
      have been developed to unravel a GRN. The DREAM project aims to clarify both
      advantages and disadvantages of these methods from an application viewpoint. An
      interesting yet surprising observation is that compared with complicated methods
      like those based on nonlinear differential equations, etc., methods based on a
      simple statistics, such as the so-called Z-score, usually perform better. A
      fundamental problem with the Z-score, however, is that direct and indirect
      regulations can not be easily distinguished. To overcome this drawback, a
      relative expression level variation (RELV) based GRN inference algorithm is
      suggested in this paper, which consists of three major steps. Firstly, on the
      basis of wild type and single gene knockout/knockdown experimental data, the
      magnitude of RELV of a gene is estimated. Secondly, probability for the existence
      of a direct regulation from a perturbed gene to a measured gene is estimated,
      which is further utilized to estimate whether a gene can be regulated by other
      genes. Finally, the normalized RELVs are modified to make genes with an estimated
      zero in-degree have smaller RELVs in magnitude than the other genes, which is
      used afterwards in queuing possibilities of the existence of direct regulations
      among genes and therefore leads to an estimate on the GRN topology. This method
      can in principle avoid the so-called cascade errors under certain situations.
      Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show
      that, compared with the Z-score based method, prediction performances can be
      substantially improved, especially the AUPR specification. Moreover, it can even
      outperform the best team of both DREAM3 and DREAM4. Furthermore, the high
      precision of the obtained most reliable predictions shows that the suggested
      algorithm may be very helpful in guiding biological experiment designs.

PMID- 22363577
TI  - Recombinant lysyl oxidase propeptide protein inhibits growth and promotes
      apoptosis of pre-existing murine breast cancer xenografts.
AB  - Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of
      cancer xenografts. Here the ability and mode of action of purified recombinant
      LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was
      determined. Experimental approaches employed were direct intratumoral injection
      (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and
      application of a slow release formulation of rLOX-PP implanted adjacent to tumors
      in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice
      were subjected to immunohistochemical and Western blot analyses for several
      markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t.
      injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and
      tumor weight at harvest on day 25 by 30% compared to control. Implantation of
      beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume
      and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of
      tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05)
      were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP
      significantly reduced the expression of proliferation markers and Erk1/2 MAP
      kinase activation, while prominent increases in apoptosis markers were observed.
      rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not
      in controls. Data provide pre-clinical findings that support proof of principle
      for the therapeutic anti-cancer potential of rLOX-PP protein formulations.

PMID- 22363579
TI  - The formation and stabilization of a novel G-quadruplex in the 5'-flanking region
      of the relaxin gene.
AB  - It has been reported that binding of STAT3 protein to the 5'-flanking region of
      the relaxin gene may result in downregulation of the relaxin expression. There is
      a Guanine(G)-rich segment located in about 3.8 Kb upstream of the relaxin gene
      and very close to the STAT3's binding site. In our study, NMR spectroscopy
      revealed the formation of G-quadruplex by this G-rich strand, and the result was
      confirmed by ESI mass spectrometry and CD spectroscopy. The theoretical structure
      of RLX G-quadruplex was constructed and refined by molecular modeling. When this
      relaxin G-quadruplex was stabilized by berberine(DeltaTm = 10 degrees C), a
      natural alkaloid from a Chinese herb, the gene expression could be up-regulated
      in a dose-dependent manner which was proved by luciferase assay. This result is
      different from the general G-quadruplex function that inhibiting the telomere
      replication or down-regulating many oncogenes expression. Therefore, our study
      reported a novel G-quadruplex in the relaxin gene and complemented the regulation
      mechanism about gene expression by G-quadruplexes.

PMID- 22363580
TI  - Language comprehension in the balance: the robustness of the action-compatibility
      effect (ACE).
AB  - How does language comprehension interact with motor activity? We investigated the
      conditions under which comprehending an action sentence affects people's balance.
      We performed two experiments to assess whether sentences describing forward or
      backward movement modulate the lateral movements made by subjects who made
      sensibility judgments about the sentences. In one experiment subjects were
      standing on a balance board and in the other they were seated on a balance board
      that was mounted on a chair. This allowed us to investigate whether the action
      compatibility effect (ACE) is robust and persists in the face of salient
      incompatibilities between sentence content and subject movement. Growth-curve
      analysis of the movement trajectories produced by the subjects in response to the
      sentences suggests that the ACE is indeed robust. Sentence content influenced
      movement trajectory despite salient inconsistencies between implied and actual
      movement. These results are interpreted in the context of the current discussion
      of embodied, or grounded, language comprehension and meaning representation.

PMID- 22363581
TI  - Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential
      correlation with tumor progression.
AB  - BACKGROUND: Histamine is an established growth factor for gastrointestinal
      malignancies. The effect of histamine is largely determined locally by the
      histamine receptor expression pattern. Histamine receptor H4 (HRH4), the newest
      member of the histamine receptor family, is positively expressed on the
      epithelium of the gastrointestinal tract, and its function remains to be
      elucidated. Previously, we reported the decreased expression of HRH4 in
      colorectal cancers and revealed its correlation with tumor proliferation. In the
      current study, we aimed to investigate the abnormalities of HRH4 gene in gastric
      carcinomas (GCs). METHODOLOGY/PRINCIPAL FINDINGS: We analyzed H4R expression in
      collected GC samples by quantitative PCR, Western blot analysis, and
      immunostaining. Our results showed that the protein and mRNA levels of HRH4 were
      reduced in some GC samples, especially in advanced GC samples. Copy number
      decrease of HRH4 gene was observed (17.6%, 23 out of 131), which was closely
      correlated with the attenuated expression of H4R. In vitro studies, using gastric
      cancer cell lines, showed that the alteration of HRH4 expression on gastric
      cancer cells influences tumor growth upon exposure to histamine.
      CONCLUSIONS/SIGNIFICANCE: We show for the first time that deletion of HRH4 gene
      is present in GC cases and is closely correlated with attenuated gene expression.
      Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated
      growth control of GC cells.

PMID- 22363583
TI  - Total catch of a red-listed marine species is an order of magnitude higher than
      official data.
AB  - Accurate information on total catch and effort is essential for successful
      fisheries management. Officially reported landings, however, may be
      underestimates of total catch in many fisheries. We investigated the fishery for
      the nationally red-listed European lobster (Homarus gammarus) in south-eastern
      Norway. Probability-based strip transect surveys were used to count buoys in the
      study area in combination with catch per unit effort data obtained independently
      from volunteer catch diaries, phone interviews, and questionnaires. We estimate
      that recreational catch accounts for 65% of total catch in the study area.
      Moreover, our results indicate that only a small proportion (24%) of lobsters
      landed commercially were sold through the legal market and documented. Total
      estimated lobster catch was nearly 14 times higher than reported officially. Our
      study highlights the need for adequate catch monitoring and data collection
      efforts in coastal areas, presents a clear warning to resource managers that
      illegal, unreported and unregulated (IUU) fisheries in coastal areas should not
      be ignored, and shows the potential impact of recreational fisheries.

PMID- 22363582
TI  - Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium
      falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors.
AB  - BACKGROUND: Traditionally, vaccine development against the blood-stage of
      Plasmodium falciparum infection has focused on recombinant protein-adjuvant
      formulations in order to induce high-titer growth-inhibitory antibody responses.
      However, to date no such vaccine encoding a blood-stage antigen(s) alone has
      induced significant protective efficacy against erythrocytic-stage infection in a
      pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess
      vaccine efficacy. Cell-mediated responses, acting in conjunction with functional
      antibodies, may be necessary for immunity against blood-stage P. falciparum. The
      development of a vaccine that could induce both cell-mediated and humoral immune
      responses would enable important proof-of-concept efficacy studies to be
      undertaken to address this question. METHODOLOGY: We conducted a Phase Ia, non
      randomized clinical trial in 16 healthy, malaria-naive adults of the chimpanzee
      adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication
      deficient viral vectored vaccines encoding two alleles (3D7 and FVO) of the P.
      falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1). ChAd63
      MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe
      and immunogenic, inducing high-level T cell responses to both alleles 3D7 (median
      2036 SFU/million PBMC) and FVO (median 1539 SFU/million PBMC), with a mixed
      CD4(+)/CD8(+) phenotype, as well as substantial AMA1-specific serum IgG responses
      (medians of 49 ug/mL and 41 ug/mL for 3D7 and FVO AMA1 respectively) that
      demonstrated growth inhibitory activity in vitro. CONCLUSIONS: ChAd63-MVA is a
      safe and highly immunogenic delivery platform for both alleles of the AMA1
      antigen in humans which warrants further efficacy testing. ChAd63-MVA is a
      promising heterologous prime-boost vaccine strategy that could be applied to
      numerous other diseases where strong cellular and humoral immune responses are
      required for protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01095055.

PMID- 22363584
TI  - The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic
      cells in a TLR3 dependent manner.
AB  - Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to
      stimulate T cells resulting in an immune response that can efficiently target the
      cancer cells. One of the critical hurdles has been the lack of IL-12p70
      production when maturating the DC, which is rectified by using the bacterial
      preparation OK432 (trade name Picibanil) to mature the cells. In order to
      identify the mechanism behind OK432 stimulation of DC, we investigated the
      contribution of different TLR to examine their involvement in IL-12p70
      production. By combining different inhibitors of TLR signaling, we demonstrate
      here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432.
      Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon
      TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The
      fact that a bacterial compound like OK432 can activate the TLR3 pathway in human
      DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70
      production, which is of great relevance in DC based cancer immunotherapy.

PMID- 22363586
TI  - Effect of Acinetobacter sp on metalaxyl degradation and metabolite profile of
      potato seedlings (Solanum tuberosum L.) alpha variety.
AB  - One of the most serious diseases in potato cultivars is caused by the pathogen
      Phytophthora infestans, which affects leaves, stems and tubers. Metalaxyl is a
      fungicide that protects potato plants from Phytophthora infestans. In Mexico,
      farmers apply metalaxyl 35 times during the cycle of potato production and the
      last application is typically 15 days before harvest. There are no records
      related to the presence of metalaxyl in potato tubers in Mexico. In the present
      study, we evaluated the effect of Acinetobacter sp on metalaxyl degradation in
      potato seedlings. The effect of bacteria and metalaxyl on the growth of potato
      seedlings was also evaluated. A metabolite profile analysis was conducted to
      determine potential molecular biomarkers produced by potato seedlings in the
      presence of Acinetobacter sp and metalaxyl. Metalaxyl did not affect the growth
      of potato seedlings. However, Acinetobacter sp strongly affected the growth of
      inoculated seedlings, as confirmed by plant length and plant fresh weights which
      were lower in inoculated potato seedlings (40% and 27%, respectively) compared to
      the controls. Acinetobacter sp also affected root formation. Inoculated potato
      seedlings showed a decrease in root formation compared to the controls. LC-MS/MS
      analysis of metalaxyl residues in potato seedlings suggests that Acinetobacter sp
      did not degrade metalaxyl. GC-TOF-MS platform was used in metabolic profiling
      studies. Statistical data analysis and metabolic pathway analysis allowed
      suggesting the alteration of metabolic pathways by both Acinetobacter sp
      infection and metalaxyl treatment. Several hundred metabolites were detected, 137
      metabolites were identified and 15 metabolic markers were suggested based on
      statistical change significance found with PLS-DA analysis. These results are
      important for better understanding the interactions of putative endophytic
      bacteria and pesticides on plants and their possible effects on plant metabolism.

PMID- 22363585
TI  - A novel framework for the comparative analysis of biological networks.
AB  - Genome sequencing projects provide nearly complete lists of the individual
      components present in an organism, but reveal little about how they work
      together. Follow-up initiatives have deciphered thousands of dynamic and context
      dependent interrelationships between gene products that need to be analyzed with
      novel bioinformatics approaches able to capture their complex emerging
      properties. Here, we present a novel framework for the alignment and comparative
      analysis of biological networks of arbitrary topology. Our strategy includes the
      prediction of likely conserved interactions, based on evolutionary distances, to
      counter the high number of missing interactions in the current interactome
      networks, and a fast assessment of the statistical significance of individual
      alignment solutions, which vastly increases its performance with respect to
      existing tools. Finally, we illustrate the biological significance of the results
      through the identification of novel complex components and potential cases of
      cross-talk between pathways and alternative signaling routes.

PMID- 22363587
TI  - Prohibitin 1 modulates mitochondrial stress-related autophagy in human colonic
      epithelial cells.
AB  - INTRODUCTION: Autophagy is an adaptive response to extracellular and
      intracellular stress by which cytoplasmic components and organelles, including
      damaged mitochondria, are degraded to promote cell survival and restore cell
      homeostasis. Certain genes involved in autophagy confer susceptibility to Crohn's
      disease. Reactive oxygen species and pro-inflammatory cytokines such as tumor
      necrosis factor alpha (TNFalpha), both of which are increased during active
      inflammatory bowel disease, promote cellular injury and autophagy via
      mitochondrial damage. Prohibitin (PHB), which plays a role in maintaining normal
      mitochondrial respiratory function, is decreased during active inflammatory bowel
      disease. Restoration of colonic epithelial PHB expression protects mice from
      experimental colitis and combats oxidative stress. In this study, we investigated
      the potential role of PHB in modulating mitochondrial stress-related autophagy in
      intestinal epithelial cells. METHODS: We measured autophagy activation in
      response to knockdown of PHB expression by RNA interference in Caco2-BBE and
      HCT116 WT and p53 null cells. The effect of exogenous PHB expression on TNFalpha-
      and IFNgamma-induced autophagy was assessed. Autophagy was inhibited using
      Bafilomycin A(1) or siATG16L1 during PHB knockdown and the affect on
      intracellular oxidative stress, mitochondrial membrane potential, and cell
      viability were determined. The requirement of intracellular ROS in siPHB-induced
      autophagy was assessed using the ROS scavenger N-acetyl-L-cysteine. RESULTS:
      TNFalpha and IFNgamma-induced autophagy inversely correlated with PHB protein
      expression. Exogenous PHB expression reduced basal autophagy and TNFalpha-induced
      autophagy. Gene silencing of PHB in epithelial cells induces mitochondrial
      autophagy via increased intracellular ROS. Inhibition of autophagy during PHB
      knockdown exacerbates mitochondrial depolarization and reduces cell viability.
      CONCLUSIONS: Decreased PHB levels coupled with dysfunctional autophagy renders
      intestinal epithelial cells susceptible to mitochondrial damage and cytotoxicity.
      Repletion of PHB may represent a therapeutic approach to combat oxidant and
      cytokine-induced mitochondrial damage in diseases such as inflammatory bowel
      disease.

PMID- 22363588
TI  - Establishment of a novel fluorescence-based method to evaluate chaperone-mediated
      autophagy in a single neuron.
AB  - BACKGROUND: Chaperone-mediated autophagy (CMA) is a selective autophagy-lysosome
      protein degradation pathway. The role of CMA in normal neuronal functions and in
      neural disease pathogenesis remains unclear, in part because there is no
      available method to monitor CMA activity at the single-cell level.
      METHODOLOGY/PRINCIPAL FINDINGS: We sought to establish a single-cell monitoring
      method by visualizing translocation of CMA substrates from the cytosol to
      lysosomes using the HaloTag (HT) system. GAPDH, a CMA substrate, was fused to HT
      (GAPDH-HT); this protein accumulated in the lysosomes of HeLa cells and cultured
      cerebellar Purkinje cells (PCs) after labeling with fluorescent dye-conjugated HT
      ligand. Lysosomal accumulation was enhanced by treatments that activate CMA and
      prevented by siRNA-mediated knockdown of LAMP2A, a lysosomal receptor for CMA,
      and by treatments that inactivate CMA. These results suggest that lysosomal
      accumulation of GAPDH-HT reflects CMA activity. Using this method, we revealed
      that mutant gammaPKC, which causes spinocerebellar ataxia type 14, decreased CMA
      activity in cultured PCs. CONCLUSION/SIGNIFICANCE: In the present study, we
      established a novel fluorescent-based method to evaluate CMA activity in a single
      neuron. This novel method should be useful and valuable for evaluating the role
      of CMA in various neuronal functions and neural disease pathogenesis.

PMID- 22363590
TI  - A novel strategy to construct yeast Saccharomyces cerevisiae strains for very
      high gravity fermentation.
AB  - Very high gravity (VHG) fermentation is aimed to considerably increase both the
      fermentation rate and the ethanol concentration, thereby reducing capital costs
      and the risk of bacterial contamination. This process results in critical issues,
      such as adverse stress factors (ie., osmotic pressure and ethanol inhibition) and
      high concentrations of metabolic byproducts which are difficult to overcome by a
      single breeding method. In the present paper, a novel strategy that combines
      metabolic engineering and genome shuffling to circumvent these limitations and
      improve the bioethanol production performance of Saccharomyces cerevisiae strains
      under VHG conditions was developed. First, in strain Z5, which performed better
      than other widely used industrial strains, the gene GPD2 encoding glycerol 3
      phosphate dehydrogenase was deleted, resulting in a mutant (Z5DeltaGPD2) with a
      lower glycerol yield and poor ethanol productivity. Second, strain Z5DeltaGPD2
      was subjected to three rounds of genome shuffling to improve its VHG fermentation
      performance, and the best performing strain SZ3-1 was obtained. Results showed
      that strain SZ3-1 not only produced less glycerol, but also increased the ethanol
      yield by up to 8% compared with the parent strain Z5. Further analysis suggested
      that the improved ethanol yield in strain SZ3-1 was mainly contributed by the
      enhanced ethanol tolerance of the strain. The differences in ethanol tolerance
      between strains Z5 and SZ3-1 were closely associated with the cell membrane fatty
      acid compositions and intracellular trehalose concentrations. Finally, genome
      rearrangements in the optimized strain were confirmed by karyotype analysis.
      Hence, a combination of genome shuffling and metabolic engineering is an
      efficient approach for the rapid improvement of yeast strains for desirable
      industrial phenotypes.

PMID- 22363589
TI  - Parental LTRs are important in a construct of a stable and efficient replication
      competent infectious molecular clone of HIV-1 CRF08_BC.
AB  - Circulating recombinant forms (CRFs) of HIV-1 have been identified in southern
      China in recent years. CRF08_BC is one of the most predominant subtypes
      circulating in China. In order to study HIV subtype biology and to provide a tool
      for biotechnological applications, the first full-length replication-competent
      infectious molecular clone harboring CRF08_BC is reported. The construction of
      this clone pBRGX indicates that a moderate-copy number vector is required for its
      amplification in E. coli. In addition, it is shown that the parental CRF08_BC
      LTRs are important for generating this efficient replication-competent infectious
      clone. These observations may aid in the construction of infectious clones from
      other subtypes. Both the pBRGX-derived virus and its parental isolate contain
      CCR5 tropism. Their full-length genomes were also sequenced, analyzed, compared
      and deposited in GenBank (JF719819 and JF719818, respectively). The availability
      of pBRGX as the first replication-competent molecular clone of CRF08_BC provides
      a useful tool for a wide range of studies of this newly emergent HIV subtype,
      including the development of HIV vaccine candidates, antiviral drug screening and
      drug resistance analysis.

PMID- 22363593
TI  - Nonparametric evaluation of quantitative traits in population-based association
      studies when the genetic model is unknown.
AB  - Statistical association between a single nucleotide polymorphism (SNP) genotype
      and a quantitative trait in genome-wide association studies is usually assessed
      using a linear regression model, or, in the case of non-normally distributed
      trait values, using the Kruskal-Wallis test. While linear regression models
      assume an additive mode of inheritance via equi-distant genotype scores, Kruskal
      Wallis test merely tests global differences in trait values associated with the
      three genotype groups. Both approaches thus exhibit suboptimal power when the
      underlying inheritance mode is dominant or recessive. Furthermore, these tests do
      not perform well in the common situations when only a few trait values are
      available in a rare genotype category (disbalance), or when the values associated
      with the three genotype categories exhibit unequal variance (variance
      heterogeneity). We propose a maximum test based on Marcus-type multiple contrast
      test for relative effect sizes. This test allows model-specific testing of either
      dominant, additive or recessive mode of inheritance, and it is robust against
      variance heterogeneity. We show how to obtain mode-specific simultaneous
      confidence intervals for the relative effect sizes to aid in interpreting the
      biological relevance of the results. Further, we discuss the use of a related all
      pairwise comparisons contrast test with range preserving confidence intervals as
      an alternative to Kruskal-Wallis heterogeneity test. We applied the proposed
      maximum test to the Bogalusa Heart Study dataset, and gained a remarkable
      increase in the power to detect association, particularly for rare genotypes. Our
      simulation study also demonstrated that the proposed non-parametric tests control
      family-wise error rate in the presence of non-normality and variance
      heterogeneity contrary to the standard parametric approaches. We provide a
      publicly available R library nparcomp that can be used to estimate simultaneous
      confidence intervals or compatible multiplicity-adjusted p-values associated with
      the proposed maximum test.

PMID- 22363591
TI  - Differing burden and epidemiology of non-Typhi Salmonella bacteremia in rural and
      urban Kenya, 2006-2009.
AB  - BACKGROUND: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa
      will likely evolve as potential co-factors, such as HIV, malaria, and
      urbanization, also change. METHODS: As part of population-based surveillance
      among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban
      Kenya from 2006-2009, blood cultures were obtained from patients presenting to
      referral clinics with fever >=38.0 degrees C or severe acute respiratory
      infection. Incidence rates were adjusted based on persons with compatible
      illnesses, but whose blood was not cultured. RESULTS: NTS accounted for 60/155
      (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites.
      The adjusted incidence in the rural site was 568/100,000 person-years, and the
      urban site was 51/100,000 person-years. In both sites, the incidence was highest
      in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site
      was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood
      NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS
      isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug
      resistant, most of which had an identical profile in Pulse Field Gel
      Electrophoresis. In the rural site, the incidence of NTS bacteremia increased
      during the study period, concomitant with rising malaria prevalence (monthly
      correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's
      correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of
      adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of
      NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal
      autopsy. CONCLUSIONS: NTS caused the majority of bacteremias in rural Kenya, but
      typhoid predominated in urban Kenya, which most likely reflects differences in
      malaria endemicity. Control measures for malaria, as well as HIV, will likely
      decrease the burden of NTS bacteremia in Africa.

PMID- 22363592
TI  - Probiotic bacteria produce conjugated linoleic acid locally in the gut that
      targets macrophage PPAR gamma to suppress colitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) therapies are modestly successful
      and associated with significant side effects. Thus, the investigation of novel
      approaches to prevent colitis is important. Probiotic bacteria can produce
      immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a
      polyunsaturated fatty acid with potent anti-inflammatory effects. This study
      aimed to investigate the cellular and molecular mechanisms underlying the anti
      inflammatory efficacy of probiotic bacteria using a mouse model of colitis.
      METHODOLOGY/PRINCIPAL FINDINGS: The immune modulatory mechanisms of VSL#3
      probiotic bacteria and CLA were investigated in a mouse model of DSS colitis.
      Colonic specimens were collected for histopathology, gene expression and flow
      cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN),
      spleen, blood and colonic lamina propria cells were phenotypically and
      functionally characterized. Fecal samples and colonic contents were collected to
      determine the effect of VSL#3 and CLA on gut microbial diversity and CLA
      production. CLA and VSL#3 treatment ameliorated colitis and decreased colonic
      bacterial diversity, a finding that correlated with decreased gut pathology.
      Colonic CLA concentrations were increased in response to probiotic bacterial
      treatment, but without systemic distribution in blood. VSL#3 and CLA decreased
      macrophage accumulation in the MLN of mice with DSS colitis. The loss of PPAR
      gamma in myeloid cells abrogated the protective effect of probiotic bacteria and
      CLA in mice with DSS colitis. CONCLUSIONS/SIGNIFICANCE: Probiotic bacteria
      modulate gut microbial diversity and favor local production of CLA in the colon
      that targets myeloid cell PPAR gamma to suppress colitis.

PMID- 22363594
TI  - Methicillin-resistant Staphylococcus aureus ST9 in pigs in Thailand.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important
      nosocomial and community-associated pathogen. Recently, livestock-associated MRSA
      (LA-MRSA) has emerged and disseminated in Europe and North America and now
      constitutes a considerable zoonotic burden in humans with risk factors of pig
      exposure, whereas the extent of the livestock reservoir is relatively unknown on
      other continents. METHODOLOGY/PRINCIPAL FINDINGS: From March through April 2011,
      MRSA was identified in pigs from 3 out of 30 production holdings in Chang Mai
      Province, Thailand. Representative isolates were subjected to molecular
      characterization and antimicrobial susceptibility testing; all isolates had
      genotypic and phenotypic characteristics of LA-MRSA previously characterized in
      the region: they belonged to ST9, lacked the lukF-lukS genes encoding Panton
      Valentine leukocidin, and were resistant to multiple non-beta-lactam
      antimicrobials. However, unlike other Asian LA-MRSA-ST9 variants, they were spa
      type t337 and harbored a different staphylococcal cassette chromosome mec IX.
      CONCLUSIONS/SIGNIFICANCE: A novel MRSA-ST9 lineage has been established in the
      pig population of Thailand, which differs substantially from LA-MRSA lineages
      found in other areas of the continent. The emergence of novel LA-MRSA lineages in
      the animal agriculture setting is worrisome and poses a serious threat to global
      public health.

PMID- 22363595
TI  - Potential geographic distribution of brown marmorated stink bug invasion
      (Halyomorpha halys).
AB  - BACKGROUND: The Brown Marmorated Stink Bug (BMSB), Halyomorpha halys (Stal)
      (Hemiptera: Pentatomidae), native to Asia, is becoming an invasive species with a
      rapidly expanding range in North America and Europe. In the US, it is a household
      pest and also caused unprecedented damage to agriculture crops. Exploring its
      climatic limits and estimating its potential geographic distribution can provide
      critical information for management strategies.  METHODOLOGY/PRINCIPALS: We used
      direct climate comparisons to explore the climatic niche occupied by native and
      invasive populations of BMSB. Ecological niche modelings based on the native
      range were used to anticipate the potential distribution of BMSB worldwide.
      Conversely, niche models based on the introduced range were used to locate the
      original invasive propagates in Asia. Areas with high invasion potential were
      identified by two niche modeling algorithms (i.e., Maxent and GARP).
      CONCLUSIONS/SIGNIFICANCE: Reduced dimensionality of environmental space improves
      native model transferability in the invade area. Projecting models from invasive
      population back to native distributional areas offers valuable information on the
      potential source regions of the invasive populations. Our models anticipated
      successfully the current disjunct distribution of BMSB in the US. The original
      propagates are hypothesized to have come from northern Japan or western Korea.
      High climate suitable areas at risk of invasion include latitudes between 30
      degrees -50 degrees  including northern Europe, northeastern North America,
      southern Australia and the North Island of New Zealand. Angola in Africa and
      Uruguay in South America also showed high climate suitability.

PMID- 22363596
TI  - Genetic insight into yield-associated traits of wheat grown in multiple rain-fed
      environments.
AB  - BACKGROUND: Grain yield is a key economic driver of successful wheat production.
      Due to its complex nature, little is known regarding its genetic control. The
      goal of this study was to identify important quantitative trait loci (QTL)
      directly and indirectly affecting grain yield using doubled haploid lines derived
      from a cross between Hanxuan 10 and Lumai 14. METHODOLOGY/PRINCIPAL FINDINGS: Ten
      yield-associated traits, including yield per plant (YP), number of spikes per
      plant (NSP), number of grains per spike (NGS), one-thousand grain weight (TGW),
      total number of spikelets per spike (TNSS), number of sterile spikelets per spike
      (NSSS), proportion of fertile spikelets per spike (PFSS), spike length (SL),
      density of spikelets per spike (DSS) and plant height (PH), were assessed across
      14 (for YP) to 23 (for TGW) year * location * water regime environments in China.
      Then, the genetic effects were partitioned into additive main effects (a),
      epistatic main effects (aa) and their environment interaction effects (ae and
      aae) by using composite interval mapping in a mixed linear model.
      CONCLUSIONS/SIGNIFICANCE: Twelve (YP) to 33 (PH) QTLs were identified on all 21
      chromosomes except 6D. QTLs were more frequently observed on chromosomes 1B, 2B,
      2D, 5A and 6B, and were concentrated in a few regions on individual chromosomes,
      exemplified by three striking yield-related QTL clusters on chromosomes 2B, 1B
      and 4B that explained the correlations between YP and other traits. The additive
      main-effect QTLs contributed more phenotypic variation than the epistasis and
      environmental interaction. Consistent with agronomic analyses, a group of progeny
      derived by selecting TGW and NGS, with higher grain yield, had an increased
      frequency of QTL for high YP, NGS, TGW, TNSS, PFSS, SL, PH and fewer NSSS, when
      compared to low yielding progeny. This indicated that it is feasible by marker
      assisted selection to facilitate wheat production.

PMID- 22363597
TI  - Identification and classification of facial familiarity in directed lying: an ERP
      study.
AB  - Recognizing familiar faces is essential to social functioning, but little is
      known about how people identify human faces and classify them in terms of
      familiarity. Face identification involves discriminating familiar faces from
      unfamiliar faces, whereas face classification involves making an intentional
      decision to classify faces as "familiar" or "unfamiliar." This study used a
      directed-lying task to explore the differentiation between identification and
      classification processes involved in the recognition of familiar faces. To
      explore this issue, the participants in this study were shown familiar and
      unfamiliar faces. They responded to these faces (i.e., as familiar or unfamiliar)
      in accordance with the instructions they were given (i.e., to lie or to tell the
      truth) while their EEG activity was recorded. Familiar faces (regardless of lying
      vs. truth) elicited significantly less negative-going N400f in the middle and
      right parietal and temporal regions than unfamiliar faces. Regardless of their
      actual familiarity, the faces that the participants classified as "familiar"
      elicited more negative-going N400f in the central and right temporal regions than
      those classified as "unfamiliar." The P600 was related primarily with the facial
      identification process. Familiar faces (regardless of lying vs. truth) elicited
      more positive-going P600f in the middle parietal and middle occipital regions.
      The results suggest that N400f and P600f play different roles in the processes
      involved in facial recognition. The N400f appears to be associated with both the
      identification (judgment of familiarity) and classification of faces, while it is
      likely that the P600f is only associated with the identification process
      (recollection of facial information). Future studies should use different
      experimental paradigms to validate the generalizability of the results of this
      study.

PMID- 22363598
TI  - Activation of the PI3K/AKT pathway in Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing
      incidence. The understanding of the molecular carcinogenesis of MCC is limited.
      Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in
      human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC
      cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of
      samples. Notably, the AKT phosphorylation was not correlated with the presence or
      absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the
      large and small T antigen by shRNA in MCV positive MCC cells did not affect
      phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and
      AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas
      mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high
      sensitivity towards the PI3K inhibitor LY-294002. This finding together with our
      observation that the PI3K/AKT pathway is activated in the majority of human MCCs
      identifies PI3K/AKT as a potential new therapeutic target for MCC patients.

PMID- 22363599
TI  - Mitosis phase enrichment with identification of mitotic centromere-associated
      kinesin as a therapeutic target in castration-resistant prostate cancer.
AB  - The recently described transcriptomic switch to a mitosis program in castration
      resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally
      targeted at this lethal stage of the disease. In this study, we showed
      upregulation of the mitosis-phase at the protein level in our cohort of 51
      clinical CRPC cases and found centrosomal aberrations to also occur
      preferentially in CRPC compared with untreated, high Gleason-grade hormone
      sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy
      resistant CRPC samples (n = 25) was performed, and the results were compared with
      data from primary chemotherapy-naive CRPC (n = 10) and hormone-sensitive prostate
      cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and
      pathways, with progression to both castration-resistant and chemotherapy
      resistant disease. The mitotic centromere-associated kinesin (MCAK) was
      identified as a novel mitosis-phase target in prostate cancer that was
      overexpressed in multiple CRPC gene-expression datasets. We found concordant gene
      expression of MCAK between our parent and murine CRPC xenograft pairs and
      increased MCAK protein expression with clinical progression of prostate cancer to
      a castration-resistant disease stage. Knockdown of MCAK arrested the growth of
      prostate cancer cells suggesting its utility as a potential therapeutic target.

PMID- 22363600
TI  - Cryptosporidium cuniculus and Giardia duodenalis in rabbits: genetic diversity
      and possible zoonotic transmission.
AB  - BACKGROUND: Cryptosporidium and Giardia are the two important zoonotic pathogens
      causing diarrhea of humans and animals worldwide. Considering the human
      cryptosporidiosis outbreak and sporadic cases caused by C. cuniculus, the
      important public health significance of G. duodenalis and little obtained
      information regarding rabbit infected with Cryptosporidium and Giardia in China,
      the aim of this study is to determine the prevalence and molecularly characterize
      Cryptosporidium and Giardia in rabbits in Heilongjiang Province, China.
      METHODOLOGY/PRINCIPAL FINDINGS: 378 fecal samples were obtained from rabbits in
      Heilongjiang Province. Cryptosporidium oocysts and Giardia cysts were detected
      using Sheather's sugar flotation technique and Lugol's iodine stain method,
      respectively. The infection rates of Cryptosporidium and Giardia were 2.38%
      (9/378) and 7.41% (28/378), respectively. Genotyping of Cryptosporidium spp. was
      done by DNA sequencing of the small subunit rRNA (SSU rRNA) gene and all the nine
      isolates were identified as Cryptosporidium cuniculus. The nine isolates were
      further subtyped using the 60-kDa glycoprotein (gp60) gene and two subtypes were
      detected, including VbA32 (n = 3) and a new subtype VbA21 (n = 6). G. duodenalis
      genotypes and subtypes were identified by sequence analysis of the
      triosephosphate isomerase (TPI) gene. The assemblage B (belonging to eight
      different subtypes B-I to B-VIII) was found in 28 G. duodenalis-positive samples.
      CONCLUSIONS/SIGNIFICANCE: The rabbits have been infected with Cryptosporidium and
      Giardia in Heilongjiang Province. The results show that the rabbits pose a threat
      to human health in the studied areas. Genotypes and subgenotypes of C. cuniculus
      and G. duodenalis in this study might present the endemic genetic
      characterization of population structure of the two parasites.

PMID- 22363602
TI  - The gut fungus Basidiobolus ranarum has a large genome and different copy numbers
      of putatively functionally redundant elongation factor genes.
AB  - Fungal genomes range in size from 2.3 Mb for the microsporidian Encephalitozoon
      intestinalis up to 8000 Mb for Entomophaga aulicae, with a mean genome size of 37
      Mb. Basidiobolus, a common inhabitant of vertebrate guts, is distantly related to
      all other fungi, and is unique in possessing both EF-1alpha and EFL genes. Using
      DNA sequencing and a quantitative PCR approach, we estimated a haploid genome
      size for Basidiobolus at 350 Mb. However, based on allelic variation, the nuclear
      genome is at least diploid, leading us to believe that the final genome size is
      at least 700 Mb. We also found that EFL was in three times the copy number of its
      putatively functionally overlapping paralog EF-1alpha. This suggests that gene or
      genome duplication may be an important feature of B. ranarum evolution, and also
      suggests that B. ranarum may have mechanisms in place that favor the preservation
      of functionally overlapping genes.

PMID- 22363601
TI  - Population-based study of Streptococcus suis infection in humans in Phayao
      Province in northern Thailand.
AB  - BACKGROUND: Streptococcus suis infection in humans has received increasing
      worldwide recognition. METHODS AND FINDINGS: A prospective study of S. suis
      infection in humans was conducted in Phayao Province in northern Thailand to
      determine the incidence and the risk behaviors of the disease in this region in
      2010. Thirty-one cases were confirmed. The case fatality rate was 16.1%, and the
      estimated incidence rate was 6.2 per 100,000 in the general population. The peak
      incidence occurred in May. The median age of the patients was 53 years and 64.5%
      were men. Consumption of raw pork products was confirmed in 22 cases and the
      median incubation period (range) was 2 days (0-11) after consumption of raw pork
      products. Isolates from 31 patients were confirmed as serotype 2 in 23 patients
      (74.2%) and serotype 14 in eight patients (25.8%). The major sequence types (STs)
      were ST1 (n = 20) for serotype 2 and ST105 (n = 8) for serotype 14. The
      epidemiological analysis suggested three possible clusters, which included 17
      cases. In the largest possible cluster of 10 cases in Chiang Kham and its
      neighboring districts in May, the source of infection in four cases was
      identified as a raw pork dish served at the same restaurant in this district.
      Microbiological analysis confirmed that three of four cases associated with
      consumption of raw pork at this restaurant were attributable to an identical
      strain of serotype 2 with ST1 and pulsotype A2. CONCLUSIONS: Our data suggest a
      high incidence rate of S. suis infection in the general population in Phayao
      Province in 2010 and confirm a cluster of three cases in 31 human cases. Food
      safety control should be strengthened especially for raw pork products in
      northern Thailand.

PMID- 22363603
TI  - Vicarious experience affects patients' treatment preferences for depression.
AB  - PURPOSE: Depression is common in primary care but often under-treated. Personal
      experiences with depression can affect adherence to therapy, but the effect of
      vicarious experience is unstudied. We sought to evaluate the association between
      a patient's vicarious experiences with depression (those of friends or family)
      and treatment preferences for depressive symptoms. METHODS: We sampled 1054
      English and/or Spanish speaking adult subjects from July through December 2008,
      randomly selected from the 2008 California Behavioral Risk Factor Survey System,
      regarding depressive symptoms and treatment preferences. We then constructed a
      unidimensional scale using item analysis that reflects attitudes about
      antidepressant pharmacotherapy. This became the dependent variable in linear
      regression analyses to examine the association between vicarious experiences and
      treatment preferences for depressive symptoms. RESULTS: Our sample was 68%
      female, 91% white, and 13% Hispanic. Age ranged from 18-94 years. Mean PHQ-9
      score was 4.3; 14.5% of respondents had a PHQ-9 score >9.0, consistent with
      active depressive symptoms. Analyses controlling for current depression symptoms
      and socio-demographic factors found that in patients both with (coefficient 1.08,
      p = 0.03) and without (coefficient 0.77, p = 0.03) a personal history of
      depression, having a vicarious experience (family and friend, respectively) with
      depression is associated with a more favorable attitude towards antidepressant
      medications. CONCLUSIONS: Patients with vicarious experiences of depression
      express more acceptance of pharmacotherapy. Conversely, patients lacking
      vicarious experiences of depression have more negative attitudes towards
      antidepressants. When discussing treatment with patients, clinicians should
      inquire about vicarious experiences of depression. This information may identify
      patients at greater risk for non-adherence and lead to more tailored patient
      specific education about treatment.

PMID- 22363604
TI  - Lesions to primary sensory and posterior parietal cortices impair recovery from
      hand paresis after stroke.
AB  - BACKGROUND: Neuroanatomical determinants of motor skill recovery after stroke are
      still poorly understood. Although lesion load onto the corticospinal tract is
      known to affect recovery, less is known about the effect of lesions to cortical
      sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory
      cortices interfere with the capacity to recover motor skills after stroke.
      METHODS: Standardized tests of motor skill and somatosensory functions were
      acquired longitudinally over nine months in 29 patients with stroke to the pre-
      and postcentral gyrus, including adjacent areas of the frontal, parietal and
      insular cortices. We derived the recovery trajectories of each patient for five
      motor subtest using least-squares curve fitting and objective model selection
      procedures for linear and exponential models. Patients were classified into
      subgroups based on their motor recovery models. Lesions were mapped onto
      diffusion weighted imaging scans and normalized into stereotaxic space using cost
      function masking. To identify critical neuranatomical regions, voxel-wise
      subtractions were calculated between subgroup lesion maps. A probabilistic
      cytoarchitectonic atlas was used to quantify of lesion extent and location.
      RESULTS: Twenty-three patients with moderate to severe initial deficits showed
      exponential recovery trajectories for motor subtests that relied on precise
      distal movements. Those that retained a chronic motor deficit had lesions that
      extended to the center of the somatosensory cortex (area 2) and the intraparietal
      sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion
      extent on this areas and somatosensory performance. The rate of recovery,
      however, depended on the lesion load onto the primary motor cortex (areas 4a,
      4p). CONCLUSIONS: Our findings support a critical role of uni-and multimodal
      somatosensory cortices in motor skill recovery. Whereas lesions to these areas
      influence recovery outcome, lesions to the primary motor cortex affect recovery
      dynamics. This points to a possible dissociation of neural substrates for
      different aspects of post-stroke recovery.

PMID- 22363605
TI  - Different localization patterns of anthocyanin species in the pericarp of black
      rice revealed by imaging mass spectrometry.
AB  - Black rice (Oryza sativa L. Japonica) contains high levels of anthocyanins in the
      pericarp and is considered an effective health-promoting food. Several studies
      have identified the molecular species of anthocyanins in black rice, but
      information about the localization of each anthocyanin species is limited because
      methodologies for investigating the localization such as determining specific
      antibodies to anthocyanin, have not yet been developed Matrix-assisted laser
      desorption/ionization imaging mass spectrometry (MALDI-IMS) is a suitable tool
      for investigating the localization of metabolites. In this study, we identified 7
      species of anthocyanin monoglycosides and 2 species of anthocyanin diglycosides
      in crude extracts from black rice by matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) analysis. We also analyzed black rice sections by
      MALDI-IMS and found 2 additional species of anthocyanin pentosides and revealed
      different localization patterns of anthocyanin species composed of different
      sugar moieties. Anthocyanin species composed of a pentose moiety (cyanidin-3-O
      pentoside and petunidin-3-O-pentoside) were localized in the entire pericarp,
      whereas anthocyanin species composed of a hexose moiety (cyanidin-3-O-hexoside
      and peonidin-3-O-hexoside) were focally localized in the dorsal pericarp. These
      results indicate that anthocyanin species composed of different sugar moieties
      exhibit different localization patterns in the pericarp of black rice. This is
      the first detailed investigation into the localization of molecular species of
      anthocyanins by MALDI-IMS.

PMID- 22363606
TI  - Transmission of infectious diseases en route to habitat hotspots.
AB  - BACKGROUND: The spread of infectious diseases in wildlife populations is
      influenced by patterns of between-host contacts. Habitat "hotspots"--places
      attracting a large numbers of individuals or social groups--can significantly
      alter contact patterns and, hence, disease propagation. Research on the
      importance of habitat hotspots in wildlife epidemiology has primarily focused on
      how inter-individual contacts occurring at the hotspot itself increase disease
      transmission. However, in territorial animals, epidemiologically important
      contacts may primarily occur as animals cross through territories of conspecifics
      en route to habitat hotspots. So far, the phenomenon has received little
      attention. Here, we investigate the importance of these contacts in the case
      where infectious individuals keep visiting the hotspots and in the case where
      these individuals are not able to travel to the hotspot any more. METHODOLOGY AND
      PRINCIPAL FINDINGS: We developed a simulation epidemiological model to
      investigate both cases in a scenario when transmission at the hotspot does not
      occur. We find that (i) hotspots still exacerbate epidemics, (ii) when infectious
      individuals do not travel to the hotspot, the most vulnerable individuals are
      those residing at intermediate distances from the hotspot rather than nearby, and
      (iii) the epidemiological vulnerability of a population is the highest when the
      number of hotspots is intermediate. CONCLUSIONS AND SIGNIFICANCE: By altering
      animal movements in their vicinity, habitat hotspots can thus strongly increase
      the spread of infectious diseases, even when disease transmission does not occur
      at the hotspot itself. Interestingly, when animals only visit the nearest
      hotspot, creating additional artificial hotspots, rather than reducing their
      number, may be an efficient disease control measure.

PMID- 22363607
TI  - Transcriptome comparison between fetal and adult mouse livers: implications for
      circadian clock mechanisms.
AB  - Microarray transcriptome analyses of fetal mouse liver did not detect circadian
      expression rhythms of clock genes or clock-controlled genes, although some
      rhythmic transcripts that were likely not driven by endogenous cellular clocks
      were identified. This finding reveals a key distinction between the circadian
      oscillators in fetal and adult mouse livers. Thus, in this study, the
      transcriptomes of fetal and adult livers were systematically compared to identify
      differences in the gene expression profiles between these two developmental
      stages. Approximately 1000 transcripts were differentially enriched between the
      fetal and adult livers. These transcripts represent genes with cellular functions
      characteristic of distinct developmental stages. Clock genes were also
      differentially expressed between the fetal and adult livers. Developmental
      differences in liver gene expression might have contributed to the differences in
      oscillation status and functional states of the cellular circadian clock between
      fetal and adult livers.

PMID- 22363609
TI  - New binding mode to TNF-alpha revealed by ubiquitin-based artificial binding
      protein.
AB  - A variety of approaches have been employed to generate binding proteins from non
      antibody scaffolds. Utilizing a beta-sheet of the human ubiquitin for paratope
      creation we obtained binding proteins against tumor necrosis factor (TNF)-alpha.
      The bioactive form of this validated pharmacological target protein is a non
      covalently linked homo-trimer. This structural feature leads to the observation
      of a certain heterogeneity concerning the binding mode of TNF-alpha binding
      molecules, for instance in terms of monomer/trimer specificity. We analyzed a
      ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular
      focus on its mode of interaction. Using enzyme-linked immunosorbent assays,
      specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal
      titration calorimetry we obtained comparable results regarding the affinity and
      detected an exothermic reaction with one ubiquitin-derived binding molecule
      binding one TNF-alpha trimer. Using NMR spectroscopy and other analytical methods
      the 1:3 stoichiometry could be confirmed. Detailed binding analysis showed that
      the interaction is affected by the detergent Tween-20. Previously, this
      phenomenon was reported only for one other type of alternative scaffold-derived
      binding proteins--designed ankyrin repeat proteins--without further
      investigation. As demonstrated by size exclusion chromatography and NMR
      spectroscopy, the presence of the detergent increases the association rate
      significantly. Since the special architecture of TNF-alpha is known to be
      modulated by detergents, the access to the recognized epitope is indicated to be
      restricted by conformational transitions within the target protein. Our results
      suggest that the ubiquitin-derived binding protein targets a new epitope on TNF
      alpha, which differs from the epitopes recognized by TNF-alpha neutralizing
      antibodies.

PMID- 22363608
TI  - Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as
      well as CD4+ 8- thymocytes and invariant NKT cells but not in Treg cells.
AB  - CD40L is essential for the development of adaptive immune responses. It is
      generally thought that CD40L expression in CD4(+) T cells is regulated
      transcriptionally and made from new mRNA following antigen recognition. However,
      imaging studies show that the majority of cognate interactions between effector
      CD4(+) T cells and APCs in vivo are too short to allow de novo CD40L synthesis.
      We previously showed that Th1 effector and memory cells store preformed CD40L
      (pCD40L) in lysosomal compartments and mobilize it onto the plasma membrane
      immediately after antigenic stimulation, suggesting that primed CD4(+) T cells
      may use pCD40L to activate APCs during brief encounters. Indeed, our recent study
      showed that pCD40L is sufficient to mediate selective activation of cognate B
      cells and trigger DC activation in vitro. In this study, we show that pCD40L is
      present in Th1 and follicular helper T cells developed during infection with
      lymphocytic choriomeningitis virus, Th2 cells in the airway of asthmatic mice,
      and Th17 cells from the CNS of animals with experimental autoimmune encephalitis
      (EAE). pCD40L is nearly absent in both natural and induced Treg cells, even in
      the presence of intense inflammation such as occurs in EAE. We also found pCD40L
      expression in CD4 single positive thymocytes and invariant NKT cells. Together,
      these results suggest that pCD40L may function in T cell development as well as
      an unexpectedly broad spectrum of innate and adaptive immune responses, while its
      expression in Treg cells is repressed to avoid compromising their suppressive
      activity.

PMID- 22363610
TI  - Pulmonary vaccination as a novel treatment for lung fibrosis.
AB  - Pulmonary fibrosis is an untreatable, uniformly fatal disease of unclear etiology
      that is the result of unremitting chronic inflammation. Recent studies have
      implicated bone marrow derived fibrocytes and M2 macrophages as playing key roles
      in propagating fibrosis. While the disease process is characterized by the
      accumulation of lymphocytes in the lung parenchyma and alveolar space, their role
      remains unclear. In this report we definitively demonstrate the ability of T
      cells to regulate lung inflammation leading to fibrosis. Specifically we
      demonstrate the ability of intranasal vaccinia vaccination to inhibit M2
      macrophage generation and fibrocyte recruitment and hence the accumulation of
      collagen and death due to pulmonary failure. Mechanistically, we demonstrate the
      ability of lung Th1 cells to prevent fibrosis as vaccinia failed to prevent
      disease in Rag-/- mice or in mice in which the T cells lacked IFN-gamma.
      Furthermore, vaccination 3 months prior to the initiation of fibrosis was able to
      mitigate the disease. Our findings clearly demonstrate the role of T cells in
      regulating pulmonary fibrosis as well as suggest that vaccinia-induced
      immunotherapy in the lung may prove to be a novel treatment approach to this
      otherwise fatal disease.

PMID- 22363611
TI  - TNFalpha-induced apoptosis enabled by CCN1/CYR61: pathways of reactive oxygen
      species generation and cytochrome c release.
AB  - Although TNFalpha is a strong inducer of apoptosis, its cytotoxicity in most
      normal cells in vitro requires blockade of NFkappaB signaling or inhibition of de
      novo protein synthesis, typically by the addition of cycloheximide. However,
      several members of CCN (CYR61/CTGF/NOV) family of extracellular matrix proteins
      enable TNFalpha-dependent apoptosis in vitro without inhibiting NFkappaB or de
      novo protein synthesis, and CCN1 (CYR61) is essential for optimal TNFalpha
      cytotoxicity in vivo. Previous studies showed that CCN1 unmasks the cytotoxicity
      of TNFalpha by binding integrins alpha(v)beta(5), alpha(6)beta(1), and the cell
      surface heparan sulfate proteoglycan syndecan 4 to induce the accumulation of a
      high level of reactive oxygen species (ROS), leading to a biphasic activation of
      JNK necessary for apoptosis. Here we show for the first time that CCN1 interacts
      with the low density lipoprotein receptor-related protein 1 (LRP1) in a protein
      complex, and that binding to LRP1 is critical for CCN1-induced ROS generation and
      apoptotic synergism with TNFalpha. We also found that neutral sphingomyelinase 1
      (nSMase1), which contributes to CCN1-induced ROS generation, is required for
      CCN1/TNFalpha-induced apoptosis. Furthermore, CCN1 promotes the activation of p53
      and p38 MAPK, which mediate enhanced cytochrome c release to amplify the
      cytotoxicity of TNFalpha. By contrast, LRP1, nSMase1, p53, and p38 MAPK are not
      required when TNFalpha-dependent apoptosis is facilitated by the presence of
      cycloheximide, indicating that they function in the CCN1 signaling pathway that
      converges with TNFalpha-induced signaling events. Since CCN1/CYR61 is a
      physiological regulator of TNFalpha cytotoxicity at least in some contexts, these
      findings may reveal important mediators of TNFalpha-induced apoptosis in vivo and
      identify potential therapeutic targets for thwarting TNFalpha-dependent tissue
      damage.

PMID- 22363612
TI  - Prolactin secretion in healthy adults is determined by gender, age and body mass
      index.
AB  - BACKGROUND: Prolactin (PRL) secretion is quantifiable as mean, peak and nadir PRL
      concentrations, degree of irregularity (ApEn, approximate entropy) and spikiness
      (brief staccato-like fluctuations). HYPOTHESIS: Distinct PRL dynamics reflect
      relatively distinct (combinations of) subject variables, such as gender, age, and
      BMI. LOCATION: Clinical Research Unit. SUBJECTS: Seventy-four healthy adults aged
      22-77 yr (41 women and 33 men), with BMI 18.3-39.4 kg/m(2). MEASURES:
      Immunofluorometric PRL assay of 10-min samples collected for 24 hours. RESULTS:
      Mean 24-h PRL concentration correlated jointly with gender (P<0.0001) and BMI (P
      = 0.01), but not with age (overall R(2) = 0.308, P<0.0001). Nadir PRL
      concentration correlated with gender only (P = 0.017) and peak PRL with gender
      (P<0.001) and negatively with age (P<0.003), overall R(2) = 0.325, P<0.0001.
      Forward-selection multivariate regression of PRL deconvolution results
      demonstrated that basal (nonpulsatile) PRL secretion tended to be associated with
      BMI (R(2) = 0.058, P = 0.03), pulsatile secretion with gender (R(2) = 0.152, P =
      0.003), and total secretion with gender and BMI (R(2) = 0.204, P<0.0001). Pulse
      mass was associated with gender (P = 0.001) and with a negative tendency to age
      (P = 0.038). In male subjects older than 50 yr (but not in women) approximate
      entropy was increased (0.942+/-0.301 vs. 1.258+/-0.267, P = 0.007) compared with
      younger men, as well as spikiness (0.363+/-0.122 vs. 0463+/-2.12, P = 0.031).
      Cosinor analysis disclosed higher mesor and amplitude in females than in men, but
      the acrophase was gender-independent. The acrophase was determined by age and BMI
      (R(2) = 0.186, P = 0.001). CONCLUSION: In healthy adults, selective combinations
      of gender, age, and BMI specify distinct PRL dynamics, thus requiring balanced
      representation of these variables in comparative PRL studies.

PMID- 22363613
TI  - In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous
      extracorporeal infusion of hyperpolarized 129Xe.
AB  - BACKGROUND: Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) permits
      high resolution, regional visualization of pulmonary ventilation. Additionally,
      its reasonably high solubility (>10%) and large chemical shift range (>200 ppm)
      in tissues allow HP (129)Xe to serve as a regional probe of pulmonary perfusion
      and gas transport, when introduced directly into the vasculature. In earlier
      work, vascular delivery was accomplished in rats by first dissolving HP (129)Xe
      in a biologically compatible carrier solution, injecting the solution into the
      vasculature, and then detecting HP (129)Xe as it emerged into the alveolar
      airspaces. Although easily implemented, this approach was constrained by the
      tolerable injection volume and the duration of the HP (129)Xe signal. METHODS AND
      PRINCIPAL FINDINGS: Here, we overcome the volume and temporal constraints imposed
      by injection, by using hydrophobic, microporous, gas-exchange membranes to
      directly and continuously infuse (129)Xe into the arterial blood of live rats
      with an extracorporeal (EC) circuit. The resulting gas-phase (129)Xe signal is
      sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent,
      3D MR images with a nominal resolution of 2*2*2 mm(3). We also show that the
      (129)Xe signal dynamics during EC infusion are well described by an analytical
      model that incorporates both mass transport into the blood and longitudinal
      relaxation. CONCLUSIONS: Extracorporeal infusion of HP (129)Xe enables rapid, 3D
      MR imaging of rat lungs and, when combined with ventilation imaging, will permit
      spatially resolved studies of the ventilation-perfusion ratio in small animals.
      Moreover, EC infusion should allow (129)Xe to be delivered elsewhere in the body
      and make possible functional and molecular imaging approaches that are currently
      not feasible using inhaled HP (129)Xe.

PMID- 22363614
TI  - Health care support issues for internationally adopted children: a qualitative
      approach to the needs and expectations of families.
AB  - BACKGROUND: Families of internationally adopted children may face specific
      problems with which general practitioners (GPs) may not be familiar. The aim of
      the study was to explore problems faced by families before, during and after the
      arrival of their internationally adopted child and to assess the usefulness of a
      specific medical structure for internationally adopted children, which could be a
      resource for the GP. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative
      study using individual semistructured guided conversations and interviewed 21
      families that had adopted a total of 26 children internationally in the Puy de
      Dome department, France, in 2003. Quantitative data were used to describe the
      pathologies diagnosed and the investigations performed.Our study showed that the
      history of these families, from the start of the adoption project to its
      achievement, is complex and warrants careful analysis. Health-care providers
      should not only consider the medical aspects of adoption, but should also be
      interested in the histories of these families, which may play a role in the
      forming of attachments between the adoptee and their adoptive parents and prevent
      further trouble during the development of the child. We also showed that adoptive
      parents have similar fears or transient difficulties that may be resolved quickly
      by listening and reassurance. Most such families would support the existence of a
      specific medical structure for internationally adopted children, which could be a
      resource for the general practitioner. However, the health-care providers
      interviewed were divided on the subject and expressed their fear that a special
      consultation could be stigmatizing to children and families.
      CONCLUSIONS/SIGNIFICANCE: A specific consultation with well-trained and
      experienced practitioners acting in close collaboration with GPs and
      paediatricians may be of help in better understanding and supporting adopted
      children and their families.

PMID- 22363616
TI  - Effect of different doses of aerobic exercise on total white blood cell (WBC) and
      WBC subfraction number in postmenopausal women: results from DREW.
AB  - BACKGROUND: Elevated total white blood cell (WBC) count is associated with an
      increased risk of coronary heart disease and death. Aerobic exercise is
      associated with lower total WBC, neutrophil, and monocyte counts. However, no
      studies have evaluated the effect of the amount of aerobic exercise (dose) on
      total WBC and WBC subfraction counts. PURPOSE: To examine the effects of 3
      different doses of aerobic exercise on changes in total WBC and WBC subfraction
      counts and independent effects of changes in fitness, adiposity, markers of
      inflammation (IL-6, TNF-alpha, C-reactive protein), fasting glucose metabolism,
      and adiponectin. METHODS: Data from 390 sedentary, overweight/obese
      postmenopausal women from the DREW study were used in these analyses. Women were
      randomized to a non-exercise control group or one of 3 exercise groups: energy
      expenditure of 4, 8, or 12 kcal kg(-1)?week(-1) (KKW) for 6 months at an
      intensity of 50% VO2peak. RESULTS: A dose-dependent decrease in total WBC counts
      (trend P = 0.002) was observed with a significant decrease in the 12KKW group (
      163.1+/-140.0 cells/uL; mean+/-95%CI) compared with the control (138.6+/-144.7
      cells/uL). A similar response was seen in the neutrophil subfraction (trend P =
      0.001) with a significant decrease in the 12KKW group (-152.6+/-115.1 cells/uL)
      compared with both the control and 4KKW groups (96.4+/-119.0 and 21.9+/-95.3
      cells/uL, respectively) and in the 8KKW group (-102.4+/-125.0 cells/uL) compared
      with the control. When divided into high/low baseline WBC categories (median
      split), a dose-dependent decrease in both total WBCs (P = 0.003) and neutrophils
      (P<0.001) was observed in women with high baseline WBC counts. The effects of
      exercise dose on total WBC and neutrophil counts persisted after accounting for
      significant independent effects of change in waist circumference and IL-6.
      CONCLUSION: Aerobic exercise training reduces total WBC and neutrophil counts, in
      a dose-dependent manner, in overweight/obese postmenopausal women and is
      especially beneficial for those with systemic low grade inflammation. CLINICAL
      TRIALS IDENTIFIER: NCT00011193.

PMID- 22363615
TI  - Potent anti-inflammatory activity of ursolic acid, a triterpenoid antioxidant, is
      mediated through suppression of NF-kappaB, AP-1 and NF-AT.
AB  - BACKGROUND: Ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, is the
      major component of many plants including apples, basil, cranberries, peppermint,
      rosemary, oregano and prunes and has been reported to possess antioxidant and
      anti-tumor properties. These properties of UA have been attributed to its ability
      to suppress NF-kappaB (nuclear factor kappa B) activation. Since NF-kappaB, in co
      ordination with NF-AT (nuclear factor of activated T cells) and AP-1(activator
      protein-1), is known to regulate inflammatory genes, we hypothesized that UA
      might exhibit potent anti-inflammatory effects. METHODOLOGY/PRINCIPAL FINDINGS:
      The anti-inflammatory effects of UA were assessed in activated T cells, B cells
      and macrophages. Effects of UA on ERK, JNK, NF-kappaB, AP-1 and NF-AT were
      studied to elucidate its mechanism of action. In vivo efficacy of UA was studied
      using mouse model of graft-versus-host disease. UA inhibited activation,
      proliferation and cytokine secretion in T cells, B cells and macrophages. UA
      inhibited mitogen-induced up-regulation of activation markers and co-stimulatory
      molecules in T and B cells. It inhibited mitogen-induced phosphorylation of ERK
      and JNK and suppressed the activation of immunoregulatory transcription factors
      NF-kappaB, NF-AT and AP-1 in lymphocytes. Treatment of cells with UA prior to
      allogenic transplantation significantly delayed induction of acute graft-versus
      host disease in mice and also significantly reduced the serum levels of pro
      inflammatory cytokines IL-6 and IFN-gamma. UA treatment inhibited T cell
      activation even when added post-mitogenic stimulation demonstrating its
      therapeutic utility as an anti-inflammatory agent. CONCLUSIONS/SIGNIFICANCE: The
      present study describes the detailed mechanism of anti-inflammatory activity of
      UA. Further, UA may find application in the treatment of inflammatory disorders.

PMID- 22363617
TI  - The mechanical behavior of mutant K14-R125P keratin bundles and networks in NEB-1
      keratinocytes.
AB  - Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that
      is caused by dominant mutations in the genes for keratin K5 or K14 proteins.
      While the link between keratin mutations and keratinocyte fragility in EBS
      patients is clear, the exact biophysical mechanisms underlying cell fragility are
      not known. In this study, we tested the hypotheses that mutant K14-R125P
      filaments and/or networks in human keratinocytes are mechanically defective in
      their response to large-scale deformations. We found that mutant filaments and
      networks exhibit no obvious defects when subjected to large uniaxial strains and
      have no negative effects on the ability of human keratinocytes to survive large
      strains. We also found that the expression of mutant K14-R125P protein has no
      effect on the morphology of the F-actin or microtubule networks or their
      responses to large strains. Disassembly of the F-actin network with Latrunculin A
      unexpectedly led to a marked decrease in stretch-induced necrosis in both WT and
      mutant cells. Overall, our results contradict the hypotheses that EBS mutant
      keratin filaments and/or networks are mechanically defective. We suggest that
      future studies should test the alternative hypothesis that keratinocytes in EBS
      cells are fragile because they possess a sparser keratin network.

PMID- 22363618
TI  - Mutant TDP-43 and FUS cause age-dependent paralysis and neurodegeneration in C.
      elegans.
AB  - Mutations in the DNA/RNA binding proteins TDP-43 and FUS are associated with
      Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.
      Intracellular accumulations of wild type TDP-43 and FUS are observed in a growing
      number of late-onset diseases suggesting that TDP-43 and FUS proteinopathies may
      contribute to multiple neurodegenerative diseases. To better understand the
      mechanisms of TDP-43 and FUS toxicity we have created transgenic Caenorhabditis
      elegans strains that express full-length, untagged human TDP-43 and FUS in the
      worm's GABAergic motor neurons. Transgenic worms expressing mutant TDP-43 and FUS
      display adult-onset, age-dependent loss of motility, progressive paralysis and
      neuronal degeneration that is distinct from wild type alleles. Additionally,
      mutant TDP-43 and FUS proteins are highly insoluble while wild type proteins
      remain soluble suggesting that protein misfolding may contribute to toxicity.
      Populations of mutant TDP-43 and FUS transgenics grown on solid media become
      paralyzed over 7 to 12 days. We have developed a liquid culture assay where the
      paralysis phenotype evolves over several hours. We introduce C. elegans
      transgenics for mutant TDP-43 and FUS motor neuron toxicity that may be used for
      rapid genetic and pharmacological suppressor screening.

PMID- 22363619
TI  - Association of mitochondrial DNA variations with lung cancer risk in a Han
      Chinese population from southwestern China.
AB  - Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and
      mutation due to the high rate of reactive oxygen species (ROS) production and
      limited DNA-repair capacity in mitochondrial. Previous studies demonstrated that
      the increased mtDNA copy number for compensation for damage, which was associated
      with cigarette smoking, has been found to be associated with lung cancer risk
      among heavy smokers. Given that the common and "non-pathological" mtDNA
      variations determine differences in oxidative phosphorylation performance and ROS
      production, an important determinant of lung cancer risk, we hypothesize that the
      mtDNA variations may play roles in lung cancer risk. To test this hypothesis, we
      conducted a case-control study to compare the frequencies of mtDNA haplogroups
      and an 822 bp mtDNA deletion between 422 lung cancer patients and 504 controls.
      Multivariate logistic regression analysis revealed that haplogroups D and F were
      related to individual lung cancer resistance (OR = 0.465, 95%CI = 0.329-0.656,
      p<0.001; and OR = 0.622, 95%CI = 0.425-0.909, p = 0.014, respectively), while
      haplogroups G and M7 might be risk factors for lung cancer (OR = 3.924, 95%CI =
      1.757-6.689, p<0.001; and OR = 2.037, 95%CI = 1.253-3.312, p = 0.004,
      respectively). Additionally, multivariate logistic regression analysis revealed
      that cigarette smoking was a risk factor for the 822 bp mtDNA deletion.
      Furthermore, the increased frequencies of the mtDNA deletion in male cigarette
      smoking subjects of combined cases and controls with haplogroup D indicated that
      the haplogroup D might be susceptible to DNA damage from external ROS caused by
      heavy cigarette smoking.

PMID- 22363620
TI  - GO-PROMTO illuminates protein membrane topologies of glycan biosynthetic enzymes
      in the Golgi apparatus of living tissues.
AB  - The Golgi apparatus is the main site of glycan biosynthesis in eukaryotes. Better
      understanding of the membrane topology of the proteins and enzymes involved can
      impart new mechanistic insights into these processes. Publically available
      bioinformatic tools provide highly variable predictions of membrane topologies
      for given proteins. Therefore we devised a non-invasive experimental method by
      which the membrane topologies of Golgi-resident proteins can be determined in the
      Golgi apparatus in living tissues. A Golgi marker was used to construct a series
      of reporters based on the principle of bimolecular fluorescence complementation.
      The reporters and proteins of interest were recombinantly fused to split halves
      of yellow fluorescent protein (YFP) and transiently co-expressed with the
      reporters in the Nicotiana benthamiana leaf tissue. Output signals were binary,
      showing either the presence or absence of fluorescence with signal morphologies
      characteristic of the Golgi apparatus and endoplasmic reticulum (ER). The method
      allows prompt and robust determinations of membrane topologies of Golgi-resident
      proteins and is termed GO-PROMTO (for GOlgi PROtein Membrane TOpology). We
      applied GO-PROMTO to examine the topologies of proteins involved in the
      biosynthesis of plant cell wall polysaccharides including xyloglucan and
      arabinan. The results suggest the existence of novel biosynthetic mechanisms
      involving transports of intermediates across Golgi membranes.

PMID- 22363621
TI  - Antagonistic actions of HLH/bHLH proteins are involved in grain length and weight
      in rice.
AB  - Grain size is a major yield component in rice, and partly controlled by the sizes
      of the lemma and palea. Molecular mechanisms controlling the sizes of these
      organs largely remain unknown. In this study, we show that an antagonistic pair
      of basic helix-loop-helix (bHLH) proteins is involved in determining rice grain
      length by controlling cell length in the lemma/palea. Overexpression of an
      atypical bHLH, named POSITIVE REGULATOR OF GRAIN LENGTH 1 (PGL1), in lemma/palea
      increased grain length and weight in transgenic rice. PGL1 is an atypical non-DNA
      binding bHLH and assumed to function as an inhibitor of a typical DNA-binding
      bHLH through heterodimerization. We identified the interaction partner of PGL1
      and named it ANTAGONIST OF PGL1 (APG). PGL1 and APG interacted in vivo and
      localized in the nucleus. As expected, silencing of APG produced the same
      phenotype as overexpression of PGL1, suggesting antagonistic roles for the two
      genes. Transcription of two known grain-length-related genes, GS3 and SRS3, was
      largely unaffected in the PGL1-overexpressing and APG-silenced plants.
      Observation of the inner epidermal cells of lemma revealed that are caused by
      increased cell length. PGL1-APG represents a new grain length and weight
      controlling pathway in which APG is a negative regulator whose function is
      inhibited by PGL1.

PMID- 22363623
TI  - The inter- and intra-unit variability of a low-cost GPS data logger/receiver to
      study human outdoor walking in view of health and clinical studies.
AB  - PURPOSE: The present study evaluates the intra- and inter-unit variability of the
      GlobalSat(r) DG100 GPS data logger/receiver (DG100) when estimating outdoor
      walking distances and speeds. METHODS: Two experiments were performed using
      healthy subjects walking on a 400 m outdoor synthetic track. The two experiments
      consisted of two different outdoor prescribed walking protocols with distances
      ranging from 50 to 400 m. Experiment 1 examined the intra-unit variability of the
      DG100 (test-retest reproducibility) when estimating walking distances. Experiment
      2 examined the inter-unit variability of four DG100 devices (unit to unit
      variability) when estimating walking distances and speeds. RESULTS: The
      coefficient of variation [95% confidence interval], for the reliability of
      estimating walking distances, was 2.8 [2.5-3.2] %. The inter-unit variability
      among the four DG100 units tested ranged from 2.8 [2.5-3.2] % to 3.9 [3.5-4.4] %
      when estimating distances and from 2.7 [2.4-3.0] % to 3.8 [3.4-4.2] % when
      estimating speeds. CONCLUSION: The present study indicates that the DG100, an
      economical and convenient GPS data logger/receiver, can be reliably used to study
      human outdoor walking activities in unobstructed conditions. This device let
      facilitate the use of GPS in studies of health and disease.

PMID- 22363622
TI  - Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar
      simplication.
AB  - In bronchopulmonary dysplasia (BPD), alveolar septae are thickened with collagen
      and alpha-smooth muscle actin, transforming growth factor (TGF)-beta-positive
      myofibroblasts. Periostin, a secreted extracellular matrix protein, is involved
      in TGF-beta-mediated fibrosis and myofibroblast differentiation. We hypothesized
      that periostin expression is required for hypoalveolarization and interstitial
      fibrosis in hyperoxia-exposed neonatal mice, an animal model for this disease. We
      also examined periostin expression in neonatal lung mesenchymal stromal cells and
      lung tissue of hyperoxia-exposed neonatal mice and human infants with BPD. Two-to
      three day-old wild-type and periostin null mice were exposed to air or 75% oxygen
      for 14 days. Mesenchymal stromal cells were isolated from tracheal aspirates of
      premature infants. Hyperoxic exposure of neonatal mice increased alveolar wall
      periostin expression, particularly in areas of interstitial thickening. Periostin
      co-localized with alpha-smooth muscle actin, suggesting synthesis by
      myofibroblasts. A similar pattern was found in lung sections of infants dying of
      BPD. Unlike wild-type mice, hyperoxia-exposed periostin null mice did not show
      larger air spaces or alpha-smooth muscle-positive myofibroblasts. Compared to
      hyperoxia-exposed wild-type mice, hyperoxia-exposed periostin null mice also
      showed reduced lung mRNA expression of alpha-smooth muscle actin, elastin, CXCL1,
      CXCL2 and CCL4. TGF-beta treatment increased mesenchymal stromal cell periostin
      expression, and periostin treatment increased TGF-beta-mediated DNA synthesis and
      myofibroblast differentiation. We conclude that periostin expression is increased
      in the lungs of hyperoxia-exposed neonatal mice and infants with BPD, and is
      required for hyperoxia-induced hypoalveolarization and interstitial fibrosis.

PMID- 22363624
TI  - Controlling the outcome of the Toll-like receptor signaling pathways.
AB  - The Toll-Like Receptors (TLRs) are proteins involved in the immune system that
      increase cytokine levels when triggered. While cytokines coordinate the response
      to infection, they appear to be detrimental to the host when reaching too high
      levels. Several studies have shown that the deletion of specific TLRs was
      beneficial for the host, as cytokine levels were decreased consequently. It is
      not clear, however, how targeting other components of the TLR pathways can
      improve the responses to infections. We applied the concept of Minimal Cut Sets
      (MCS) to the ihsTLR v1.0 model of the TLR pathways to determine sets of reactions
      whose knockouts disrupt these pathways. We decomposed the TLR network into 34
      modules and determined signatures for each MCS, i.e. the list of targeted
      modules. We uncovered 2,669 MCS organized in 68 signatures. Very few MCS targeted
      directly the TLRs, indicating that they may not be efficient targets for
      controlling these pathways. We mapped the species of the TLR network to genes in
      human and mouse, and determined more than 10,000 Essential Gene Sets (EGS). Each
      EGS provides genes whose deletion suppresses the network's outputs.

PMID- 22363625
TI  - The BRG1 chromatin remodeler protects against ovarian cysts, uterine tumors, and
      mammary tumors in a lineage-specific manner.
AB  - The BRG1 catalytic subunit of SWI/SNF-related complexes is required for mammalian
      development as exemplified by the early embryonic lethality of Brg1 null
      homozygous mice. BRG1 is also a tumor suppressor and, in mice, 10% of
      heterozygous (Brg1(null/+)) females develop mammary tumors. We now demonstrate
      that BRG1 mRNA and protein are expressed in both the luminal and basal cells of
      the mammary gland, raising the question of which lineage requires BRG1 to promote
      mammary homeostasis and prevent oncogenic transformation. To investigate this
      question, we utilized Wap-Cre to mutate both Brg1 floxed alleles in the luminal
      cells of the mammary epithelium of pregnant mice where WAP is exclusively
      expressed within the mammary gland. Interestingly, we found that Brg1(Wap-Cre)
      conditional homozygotes lactated normally and did not develop mammary tumors even
      when they were maintained on a Brm-deficient background. However, Brg1(Wap-Cre)
      mutants did develop ovarian cysts and uterine tumors. Analysis of these latter
      tissues showed that both, like the mammary gland, contain cells that normally
      express Brg1 and Wap. Thus, tumor formation in Brg1 mutant mice appears to be
      confined to particular cell types that require BRG1 and also express Wap. Our
      results now show that such cells exist both in the ovary and the uterus but not
      in either the luminal or the basal compartments of the mammary gland. Taken
      together, these findings indicate that SWI/SNF-related complexes are dispensable
      in the luminal cells of the mammary gland and therefore argue against the notion
      that SWI/SNF-related complexes are essential for cell survival. These findings
      also suggest that the tumor-suppressor activity of BRG1 is restricted to the
      basal cells of the mammary gland and demonstrate that this function extends to
      other female reproductive organs, consistent with recent observations of
      recurrent ARID1A/BAF250a mutations in human ovarian and endometrial tumors.

PMID- 22363626
TI  - BarA-UvrY two-component system regulates virulence of uropathogenic E. coli
      CFT073.
AB  - Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E.
      coli, cause ~80% of community-acquired urinary tract infections (UTI) in humans.
      UPEC initiates its colonization in epithelial cells lining the urinary tract with
      a complicated life cycle, replicating and persisting in intracellular and
      extracellular niches. Consequently, UPEC causes cystitis and more severe form of
      pyelonephritis. To further understand the virulence characteristics of UPEC, we
      investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC
      virulence. Our results showed that mutation of BarA-UvrY TCS significantly
      decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract
      infection, chicken embryo killing assay, and cytotoxicity assay on human kidney
      and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene
      reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory
      cytokines (TNF-alpha and IL-6) and chemokine (IL-8). The virulence phenotype was
      restored similar to that of wild-type by complementation of either barA or uvrY
      gene in trans. In addition, we discussed a possible link between the BarA-UvrY
      TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall,
      this study provides the evidences for BarA-UvrY TCS regulates the virulence of
      UPEC CFT073 and may point to mechanisms by which virulence regulations are
      observed in different ways may control the long-term survival of UPEC in the
      urinary tract.

PMID- 22363627
TI  - Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo
      and in vitro.
AB  - Liver fibrosis is a major cause of liver failure, but treatment remains
      ineffective. In the present study, we investigated the mechanisms and anti
      hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis
      induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimulated rat
      hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated
      CCl(4)-induced liver fibrosis and functional impairment in a dosage-dependent
      manner, including blockade of the activation of HSC as determined by inhibiting
      de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an
      increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on
      fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF
      beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the
      activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms
      of AA were further detected in vitro in HSC-T6. Addition of AA significantly
      induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced
      Smad2/3 activation, myofibroblast transformation, and collagen matrix expression
      in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells
      prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in
      response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti
      fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA
      may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent
      inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by
      which AA protects liver from injury.

PMID- 22363628
TI  - Spontaneous voice gender imitation abilities in adult speakers.
AB  - BACKGROUND: The frequency components of the human voice play a major role in
      signalling the gender of the speaker. A voice imitation study was conducted to
      investigate individuals' ability to make behavioural adjustments to fundamental
      frequency (F0), and formants (Fi) in order to manipulate their expression of
      voice gender. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two native British-English
      adult speakers were asked to read out loud different types of text (words,
      sentence, passage) using their normal voice and then while sounding as
      'masculine' and 'feminine' as possible. Overall, the results show that both men
      and women raised their F0 and Fi when feminising their voice, and lowered their
      F0 and Fi when masculinising their voice. CONCLUSIONS/SIGNIFICANCE: These
      observations suggest that adult speakers are capable of spontaneous glottal and
      vocal tract length adjustments to express masculinity and femininity in their
      voice. These results point to a "gender code", where speakers make a
      conventionalized use of the existing sex dimorphism to vary the expression of
      their gender and gender-related attributes.

PMID- 22363629
TI  - Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at
      the level of neutrophil reactive oxygen species (ROS) production.
AB  - Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion
      associated mortality that can occur with any type of transfusion and is thought
      to be primarily due to donor antibodies activating pulmonary neutrophils in
      recipients. Recently, a large prospective case controlled clinical study of
      cardiac surgery patients demonstrated that despite implementation of male donors,
      a high incidence of TRALI still occurred and suggested a need for additional
      interventions in susceptible patient populations. To examine if intravenous
      immunoglobulin (IVIg) may be effective, a murine model of antibody-mediated acute
      lung injury that approximates human TRALI was examined. When BALB/c mice were
      injected with the anti-major histocompatibility complex class I antibody 34-1-2s,
      mild shock (reduced rectal temperature) and respiratory distress (dyspnea) were
      observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented
      these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID
      mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice
      treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry
      ratios) and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours
      before 34-1-2s administration completely protected the mice from all adverse
      events. Treatment with IVIg after symptoms began also reduced lung damage and
      mortality. While the prophylactic IVIg administration did not affect 34-1-2s
      induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from
      the IVIg-treated mice displayed no spontaneous ROS production nor could they be
      stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg
      prevents murine antibody-mediated acute lung injury at the level of neutrophil
      ROS production and thus, alleviating tissue damage.

PMID- 22363630
TI  - Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative
      splicing and nonsense-mediated mRNA decay.
AB  - 5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of
      leukotrienes (LT), a group of inflammatory lipid mediators derived from
      arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by
      alternative splicing and nonsense-mediated mRNA decay (NMD). In the present
      study, we report the identification of 2 truncated transcripts and 4 novel 5-LO
      splice variants containing premature termination codons (PTC). The
      characterization of one of the splice variants, 5-LODelta3, revealed that it is a
      target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the
      human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LODelta3
      mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell
      differentiation alters the composition or function of the NMD complex. In
      contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown.
      Thus, the data suggest that the coupling of alternative splicing and NMD is
      involved in the regulation of 5-LO gene expression.

PMID- 22363631
TI  - Protective gene expression changes elicited by an inherited defect in
      photoreceptor structure.
AB  - Inherited defects in retinal photoreceptor structure impair visual transduction,
      disrupt relationship with the retinal pigment epithelium (RPE), and compromise
      cell viability. A variety of progressive retinal degenerative diseases can
      result, and knowledge of disease etiology remains incomplete. To investigate
      pathogenic mechanisms in such instances, we have characterized rod photoreceptor
      and retinal gene expression changes in response to a defined insult to
      photoreceptor structure, using the retinal degeneration slow (rds) mouse model.
      Global gene expression profiling was performed on flow-sorted rds and wild-type
      rod photoreceptors immediately prior and subsequent to times at which OSs are
      normally elaborated. Dysregulated genes were identified via microarray
      hybridization, and selected candidates were validated using quantitative PCR
      analyses. Both the array and qPCR data revealed that gene expression changes were
      generally modest and dispersed amongst a variety of known functional networks.
      Although genes showing major (>5-fold) differential expression were identified in
      a few instances, nearly all displayed transient temporal profiles, returning to
      WT levels by postnatal day (P) 21. These observations suggest that major defects
      in photoreceptor cell structure may induce early homeostatic responses, which
      function in a protective manner to promote cell viability. We identified a single
      key gene, Egr1, that was dysregulated in a sustained fashion in rds rod
      photoreceptors and retina. Egr1 upregulation was associated with microglial
      activation and migration into the outer retina at times subsequent to the major
      peak of photoreceptor cell death. Interestingly, this response was accompanied by
      neurotrophic factor upregulation. We hypothesize that activation of Egr1 and
      neurotrophic factors may represent a protective immune mechanism which
      contributes to the characteristically slow retinal degeneration of the rds mouse
      model.

PMID- 22363632
TI  - In the eye of the beholder: reduced threat-bias and increased gaze-imitation
      towards reward in relation to trait anger.
AB  - The gaze of a fearful face silently signals a potential threat's location, while
      the happy-gaze communicates the location of impending reward. Imitating such gaze
      shifts is an automatic form of social interaction that promotes survival of
      individual and group. Evidence from gaze-cueing studies suggests that covert
      allocation of attention to another individual's gaze-direction is facilitated
      when threat is communicated and further enhanced by trait anxiety. We used novel
      eye-tracking techniques to assess whether dynamic fearful and happy facial
      expressions actually facilitate automatic gaze-imitation. We show that this
      actual gaze-imitation effect is stronger when threat is signaled, but not further
      enhanced by trait anxiety. Instead, trait anger predicts facilitated gaze
      imitation to reward, and to reward compared to threat. These results agree with
      an increasing body of evidence on trait anger sensitivity to reward.

PMID- 22363633
TI  - Small RNAs targeting transcription start site induce heparanase silencing through
      interference with transcription initiation in human cancer cells.
AB  - Heparanase (HPA), an endo-h-D-glucuronidase that cleaves the heparan sulfate
      chain of heparan sulfate proteoglycans, is overexpressed in majority of human
      cancers. Recent evidence suggests that small interfering RNA (siRNA) induces
      transcriptional gene silencing (TGS) in human cells. In this study, transfection
      of siRNA against -9/+10 bp (siH3), but not -174/-155 bp (siH1) or -134/-115 bp
      (siH2) region relative to transcription start site (TSS) locating at 101 bp
      upstream of the translation start site, resulted in TGS of heparanase in human
      prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific
      manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA
      methylation of CpG islands within heparanase promoter in siH3-transfected cells.
      The TGS of heparanase did not involve changes of epigenetic markers histone H3
      lysine 9 dimethylation (H3K9me2), histone H3 lysine 27 trimethylation (H3K27me3)
      or active chromatin marker acetylated histone H3 (AcH3). The regulation of
      alternative splicing was not involved in siH3-mediated TGS. Instead, siH3
      interfered with transcription initiation via decreasing the binding of both RNA
      polymerase II and transcription factor II B (TFIIB), but not the binding of
      transcription factors Sp1 or early growth response 1, on the heparanase promoter.
      Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA
      polymerase II and TFIIB on heparanase promoter, and were necessary in siH3
      induced TGS of heparanase. Stable transfection of the short hairpin RNA construct
      targeting heparanase TSS (-9/+10 bp) into cancer cells, resulted in decreased
      proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and
      in athymic mice models. These results suggest that small RNAs targeting TSS can
      induce TGS of heparanase via interference with transcription initiation, and
      significantly suppress the tumor growth, invasion, metastasis and angiogenesis of
      cancer cells.

PMID- 22363636
TI  - Quantitative modeling of Cerenkov light production efficiency from medical
      radionuclides.
AB  - There has been recent and growing interest in applying Cerenkov radiation (CR)
      for biological applications. Knowledge of the production efficiency and other
      characteristics of the CR produced by various radionuclides would help in
      accessing the feasibility of proposed applications and guide the choice of
      radionuclides. To generate this information we developed models of CR production
      efficiency based on the Frank-Tamm equation and models of CR distribution based
      on Monte-Carlo simulations of photon and beta particle transport. All models were
      validated against direct measurements using multiple radionuclides and then
      applied to a number of radionuclides commonly used in biomedical applications. We
      show that two radionuclides, Ac-225 and In-111, which have been reported to
      produce CR in water, do not in fact produce CR directly. We also propose a simple
      means of using this information to calibrate high sensitivity luminescence
      imaging systems and show evidence suggesting that this calibration may be more
      accurate than methods in routine current use.

PMID- 22363635
TI  - Exendin-4 improves steatohepatitis by increasing Sirt1 expression in high-fat
      diet-induced obese C57BL/6J mice.
AB  - The effects of exendin-4 on Sirt1 expression as a mechanism of reducing fatty
      liver have not been previously reported. Therefore, we investigated whether the
      beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1
      in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture
      models. Exendin-4 treatment decreased body weight, serum free fatty acid (FA),
      and triglyceride levels in HF-induced obese C57BL/6J mice. Histological analysis
      showed that exendin-4 reversed HF-induced hepatic accumulation of lipids and
      inflammation. Exendin-4 treatment increased mRNA and protein expression of Sirt1
      and its downstream factor, AMPK, in vivo and also induced genes associated with
      FA oxidation and glucose metabolism. In addition, a significant increase in the
      hepatic expression of Lkb1 and Nampt mRNA was observed in exendin-4-treated
      groups. We also observed increased expression of phospho-Foxo1 and GLUT2, which
      are involved in hepatic glucose metabolism. In HepG2 and Huh7 cells, mRNA and
      protein expressions of GLP-1R were increased by exendin-4 treatment in a dose
      dependent manner. Exendin-4 enhanced protein expression of Sirt1 and phospho
      AMPKalpha in HepG2 cells treated with 0.4 mM palmitic acid. We also found that
      Sirt1 was an upstream regulator of AMPK in hepatocytes. A novel finding of this
      study was the observation that expression of GLP-1R is proportional to exendin-4
      concentration and exendin-4 could attenuate fatty liver through activation of
      Sirt1.

PMID- 22363634
TI  - alpha1Proteinase inhibitor regulates CD4+ lymphocyte levels and is rate limiting
      in HIV-1 disease.
AB  - BACKGROUND: The regulation of adult stem cell migration through human
      hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4
      (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE
      is located on the cell surface (HLE(CS)), it acts not as a proteinase, but as a
      receptor for alpha(1)proteinase inhibitor (alpha(1)PI, alpha(1)antitrypsin,
      SerpinA1). Binding of alpha(1)PI to HLE(CS) forms a motogenic complex. We
      previously demonstrated that alpha(1)PI deficiency attends HIV-1 disease and that
      alpha(1)PI augmentation produces increased numbers of immunocompetent circulating
      CD4(+) lymphocytes. Herein we investigated the mechanism underlying the
      alpha(1)PI deficiency that attends HIV-1 infection. METHODS AND FINDINGS: Active
      alpha(1)PI in HIV-1 subjects (median 17 uM, n = 35) was significantly below
      normal (median 36 uM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4(+)
      lymphocytes were correlated with the combined factors alpha(1)PI, HLE(CS) (+)
      lymphocytes, and CXCR4(+) lymphocytes (r(2) = 0.91, p<0.001, n = 30), but not
      CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/ul, CD4(+) lymphocytes
      were correlated solely with active alpha(1)PI (r(2) = 0.93, p<0.0001, n = 26).
      The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is
      shown to bind and inactivate human alpha(1)PI. Chimpanzee alpha(1)PI differs from
      human alpha(1)PI by a single amino acid within the 3F5-binding epitope. Unlike
      human alpha(1)PI, chimpanzee alpha(1)PI did not bind 3F5 or become depleted
      following HIV-1 challenge, consistent with the normal CD4(+) lymphocyte levels
      and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-alpha(1)PI
      immune complexes correlated with decreased CD4(+) lymphocytes in HIV-1 subjects.
      CONCLUSIONS: This report identifies an autoimmune component of HIV-1 disease that
      can be overcome therapeutically. Importantly, results identify an achievable
      vaccine modification with the novel objective to protect against AIDS as opposed
      to the current objective to protect against HIV-1 infection.

PMID- 22363637
TI  - Variants in exon 11 of MEF2A gene and coronary artery disease: evidence from a
      case-control study, systematic review, and meta-analysis.
AB  - BACKGROUND: Coronary artery disease (CAD) is the most common heart disease
      worldwide. Association of CAD with variants in the myocyte enhancer factor 2A
      (MEF2A) gene, the first identified CAD-causing gene, has attracted special
      attention but the results are controversial. We aimed to evaluate this genetic
      association via a case-control study and meta-analysis. METHODOLOGY/PRINCIPAL
      FINDINGS: We performed a case-control association study to investigate the
      relationship between variations in exon 11 of MEF2A gene and CAD in 1045 sporadic
      patients and 1008 controls enrolled angiographically among southern Chinese
      population, and then the data from this study were compared and discussed in a
      systematic review and meta-analysis with all available published studies on MEF2A
      gene and CAD. In total, eight variants were identified (21-bp deletion, CAG
      repeats, CCG repeats, a CCA deletion and four SNPs). No significant link was
      observed between the common (CAG)(n) polymorphism and CAD, whereas the rare 21-bp
      deletion was detected only in five affected individuals. The meta-analysis of
      (CAG)(n) polymorphism and CAD risk, including nine studies with 3801 CAD patients
      and 4020 controls, also provided no convincing evidence for the genetic
      association, even upon stratification by race (mainly Whites and Chinese).
      However, the 21-bp deletion was regarded as a potentially logical, albeit
      undetermined, candidate for CAD in the following systematic review.
      CONCLUSIONS/SIGNIFICANCE: Our findings failed to demonstrate a correlation
      between (CAG)(n) polymorphism with CAD, however, we concluded that the rare 21-bp
      deletion might have a more compelling effect on CAD than the common (CAG)(n)
      polymorphism, and MEF2A genetic variant might be a rare but specific cause of
      CAD/MI.

PMID- 22363638
TI  - Asymmetric stochastic switching driven by intrinsic molecular noise.
AB  - Low-copy-number molecules are involved in many functions in cells. The intrinsic
      fluctuations of these numbers can enable stochastic switching between multiple
      steady states, inducing phenotypic variability. Herein we present a theoretical
      and computational study based on Master Equations and Fokker-Planck and Langevin
      descriptions of stochastic switching for a genetic circuit of autoactivation. We
      show that in this circuit the intrinsic fluctuations arising from low-copy
      numbers, which are inherently state-dependent, drive asymmetric switching. These
      theoretical results are consistent with experimental data that have been reported
      for the bistable system of the gallactose signaling network in yeast. Our study
      unravels that intrinsic fluctuations, while not required to describe bistability,
      are fundamental to understand stochastic switching and the dynamical relative
      stability of multiple states.

PMID- 22363639
TI  - Structuring of bacterioplankton diversity in a large tropical bay.
AB  - Structuring of bacterioplanktonic populations and factors that determine the
      structuring of specific niche partitions have been demonstrated only for a
      limited number of colder water environments. In order to better understand the
      physical chemical and biological parameters that may influence bacterioplankton
      diversity and abundance, we examined their productivity, abundance and diversity
      in the second largest Brazilian tropical bay (Guanabara Bay, GB), as well as
      seawater physical chemical and biological parameters of GB. The inner bay
      location with higher nutrient input favored higher microbial (including vibrio)
      growth. Metagenomic analysis revealed a predominance of Gammaproteobacteria in
      this location, while GB locations with lower nutrient concentration favored
      Alphaproteobacteria and Flavobacteria. According to the subsystems (SEED)
      functional analysis, GB has a distinctive metabolic signature, comprising a
      higher number of sequences in the metabolism of phosphorus and aromatic compounds
      and a lower number of sequences in the photosynthesis subsystem. The apparent
      phosphorus limitation appears to influence the GB metagenomic signature of the
      three locations. Phosphorus is also one of the main factors determining changes
      in the abundance of planktonic vibrios, suggesting that nutrient limitation can
      be observed at community (metagenomic) and population levels (total prokaryote
      and vibrio counts).

PMID- 22363640
TI  - High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS
      versus increased risks due to pig-keeping and house construction.
AB  - BACKGROUND: African countries are scaling up malaria interventions, especially
      insecticide treated nets (ITN) and indoor residual spraying (IRS), for which
      ambitious coverage targets have been set. In spite of these efforts infection
      prevalence remains high in many parts of the continent. This study investigated
      risk factors for malaria infection in children using three malaria indicator
      surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the
      effects of keeping farm animals and of the construction material of roofs of
      houses and other potential risk factors associated with malaria infection in
      children were assessed. METHODS: Cross-sectional community-based surveys were
      conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1-15
      years) from 2748 households were included in the study. All children were
      screened for malaria by rapid diagnostic tests. Caregiver interviews were used to
      assess household demographic and wealth characteristics and ITN and IRS coverage.
      Associations between malaria infection, vector control interventions and
      potential risk factors were assessed. RESULTS: Overall, the prevalence of malaria
      infection was 47.8% (95%CI: 38.7%-57.1%) in children 1-15 years of age, less than
      a quarter of children (23.1%, 95%CI: 19.1%-27.6%) were sleeping under ITN and
      almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%
      77.0%). Protective factors that were independently associated with malaria
      infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio
      (OR)= 0.6; 95%CI: 0.4-0.9); additional protection due to sleeping under ITN in an
      IRS treated house (OR = 0.5; 95%CI: 0.3-0.7) versus sleeping in an unsprayed
      house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI:
      0.5-0.7) versus parents with no education. Increased risk of infection was
      associated with: current fever (OR = 1.2; 95%CI: 1.0-1.5) versus no fever; pig
      keeping (OR = 3.2; 95%CI: 2.1-4.9) versus not keeping pigs; living in houses with
      a grass roof (OR = 1.7; 95%CI: 1.3-2.4) versus other roofing materials and bigger
      household size (8-15 people: OR = 1.6; 95%CI: 1.3-2.1) versus small households (1
      4 persons). CONCLUSION: Malaria infection among children under 15 years of age in
      Zambezia remained high but conventional malaria vector control methods, in
      particular IRS, provided effective means of protection. Household ownership of
      farm animals, particularly pigs, and living in houses with a grass roof were
      independently associated with increased risk of infection, even after allowing
      for household wealth. To reduce the burden of malaria, national control programs
      need to ensure high coverage of effective IRS and promote the use of ITNs,
      particularly in households with elevated risks of infection, such as those
      keeping farm animals, and those with grass roofs.

PMID- 22363642
TI  - Chromatin states accurately classify cell differentiation stages.
AB  - Gene expression is controlled by the concerted interactions between transcription
      factors and chromatin regulators. While recent studies have identified global
      chromatin state changes across cell-types, it remains unclear to what extent
      these changes are co-regulated during cell-differentiation. Here we present a
      comprehensive computational analysis by assembling a large dataset containing
      genome-wide occupancy information of 5 histone modifications in 27 human cell
      lines (including 24 normal and 3 cancer cell lines) obtained from the public
      domain, followed by independent analysis at three different representations. We
      classified the differentiation stage of a cell-type based on its genome-wide
      pattern of chromatin states, and found that our method was able to identify
      normal cell lines with nearly 100% accuracy. We then applied our model to
      classify the cancer cell lines and found that each can be unequivocally
      classified as differentiated cells. The differences can be in part explained by
      the differential activities of three regulatory modules associated with embryonic
      stem cells. We also found that the "hotspot" genes, whose chromatin states change
      dynamically in accordance to the differentiation stage, are not randomly
      distributed across the genome but tend to be embedded in multi-gene chromatin
      domains, and that specialized gene clusters tend to be embedded in stably
      occupied domains.

PMID- 22363641
TI  - Ligand-induced movements of inner transmembrane helices of Glut1 revealed by
      chemical cross-linking of di-cysteine mutants.
AB  - The relative orientation and proximity of the pseudo-symmetrical inner
      transmembrane helical pairs 5/8 and 2/11 of Glut1 were analyzed by chemical cross
      linking of di-cysteine mutants. Thirteen functional di-cysteine mutants were
      created from a C-less Glut1 reporter construct containing cysteine substitutions
      in helices 5 and 8 or helices 2 and 11. The mutants were expressed in Xenopus
      oocytes and the sensitivity of each mutant to intramolecular cross-linking by two
      homobifunctional thiol-specific reagents was ascertained by protease cleavage
      followed by immunoblot analysis. Five of 9 mutants with cysteine residues
      predicted to lie in close proximity to each other were susceptible to cross
      linking by one or both reagents. None of 4 mutants with cysteine substitutions
      predicted to lie on opposite faces of their respective helices was susceptible to
      cross-linking. Additionally, the cross-linking of a di-cysteine pair (A70C/M420C,
      helices 2/11) predicted to lie near the exoplasmic face of the membrane was
      stimulated by ethylidene glucose, a non-transported glucose analog that
      preferentially binds to the exofacial substrate-binding site, suggesting that the
      binding of this ligand stimulates the closure of helices at the exoplasmic face
      of the membrane. In contrast, the cross-linking of a second di-cysteine pair
      (T158C/L325, helices 5/8), predicted to lie near the cytoplasmic face of the
      membrane, was stimulated by cytochalasin B, a glucose transport inhibitor that
      competitively inhibits substrate efflux, suggesting that this compound recruits
      the transporter to a conformational state in which closure of inner helices
      occurs at the cytoplasmic face of the membrane. This observation provides a
      structural explanation for the competitive inhibition of substrate efflux by
      cytochalasin B. These data indicate that the binding of competitive inhibitors of
      glucose efflux or influx induce occluded states in the transporter in which
      substrate is excluded from the exofacial or endofacial binding site.

PMID- 22363643
TI  - Propagation of epileptiform events across the corpus callosum in a cingulate
      cortical slice preparation.
AB  - We report on a novel mouse in vitro brain slice preparation that contains intact
      callosal axons connecting anterior cingulate cortices (ACC). Callosal connections
      are demonstrated by the ability to regularly record epileptiform events between
      hemispheres (bilateral events). That the correlation of these events depends on
      the callosum is demonstrated by the bisection of the callosum in vitro.
      Epileptiform events are evoked with four different methods: (1) bath application
      of bicuculline (a GABA-A antagonist); (2) bicuculline+MK801 (an NMDA receptor
      antagonist), (3) a zero magnesium extracellular solution (0Mg); (4) focal
      application of bicuculline to a single cortical hemisphere. Significant increases
      in the number of epileptiform events, as well as increases in the ratio of
      bilateral events to unilateral events, are observed during bath applications of
      bicuculline, but not during applications of bicuculline+MK-801. Long ictal-like
      events (defined as events >20 seconds) are only observed in 0Mg. Whole cell patch
      clamp recordings of single neurons reveal strong feedforward inhibition during
      focal epileptiform events in the contralateral hemisphere. Within the ACC, we
      find differences between the rostral areas of ACC vs. caudal ACC in terms of
      connectivity between hemispheres, with the caudal regions demonstrating shorter
      interhemispheric latencies. The morphologies of many patch clamped neurons show
      callosally-spanning axons, again demonstrating intact callosal circuits in this
      in vitro preparation.

PMID- 22363644
TI  - Loss of the tumor suppressor Pten promotes proliferation of Drosophila
      melanogaster cells in vitro and gives rise to continuous cell lines.
AB  - In vivo analysis of Drosophila melanogaster has enhanced our understanding of
      many biological processes, notably the mechanisms of heredity and development.
      While in vivo analysis of mutants has been a strength of the field, analyzing fly
      cells in culture is valuable for cell biological, biochemical and whole genome
      approaches in which large numbers of homogeneous cells are required. An efficient
      genetic method to derive Drosophila cell lines using expression of an oncogenic
      form of Ras (Ras(V12)) has been developed. Mutations in tumor suppressors, which
      are known to cause cell hyperproliferation in vivo, could provide another method
      for generating Drosophila cell lines. Here we screened Drosophila tumor
      suppressor mutations to test if they promoted cell proliferation in vitro. We
      generated primary cultures and determined when patches of proliferating cells
      first emerged. These cells emerged on average at 37 days in wild-type cultures.
      Using this assay we found that a Pten mutation had a strong effect. Patches of
      proliferating cells appeared on average at 11 days and the cultures became
      confluent in about 3 weeks, which is similar to the timeframe for cultures
      expressing Ras(V12). Three Pten mutant cell lines were generated and these have
      now been cultured for between 250 and 630 cell doublings suggesting the life of
      the mutant cells is likely to be indefinite. We conclude that the use of Pten
      mutants is a powerful means to derive new Drosophila cell lines.

PMID- 22363645
TI  - CRF-like diuretic hormone negatively affects both feeding and reproduction in the
      desert locust, Schistocerca gregaria.
AB  - Diuretic hormones (DH) related to the vertebrate Corticotropin Releasing Factor
      (CRF) have been identified in diverse insect species. In the migratory locust,
      Locusta migratoria, the CRF-like DH (CRF/DH) is localized in the same
      neurosecretory cells as the Ovary Maturating Parsin (OMP), a neurohormone that
      stimulates oocyte growth, vitellogenesis and hemolymph ecdysteroid levels in
      adult female locusts. In this study, we investigated whether CRF-like DH can
      influence feeding and reproduction in the desert locust, Schistocerca gregaria.
      We identified two highly similar S. gregaria CRF-like DH precursor cDNAs, each of
      which also encodes an OMP isoform. Alignment with other insect CRF-like DH
      precursors shows relatively high conservation of the CRF/DH sequence while the
      precursor region corresponding to OMP is not well conserved. Quantitative real
      time RT-PCR revealed that the precursor transcripts mainly occur in the central
      nervous system and their highest expression level was observed in the brain.
      Injection of locust CRF/DH caused a significantly reduced food intake, while RNAi
      knockdown stimulated food intake. Therefore, our data indicate that CRF-like DH
      induces satiety. Furthermore, injection of CRF/DH in adult females retarded
      oocyte growth and caused lower ecdysteroid titers in hemolymph and ovaries, while
      RNAi knockdown resulted in opposite effects. The observed effects of CRF/DH may
      be part of a wider repertoire of neurohormonal activities, constituting an
      integrating control system that affects food intake and excretion, as well as
      anabolic processes like oocyte growth and ecdysteroidogenesis, following a meal.
      Our discussion about the functional relationship between CRF/DH and OMP led to
      the hypothesis that OMP may possibly act as a monitoring peptide that can elicit
      negative feedback effects.

PMID- 22363646
TI  - Activating transcription factor 4 confers a multidrug resistance phenotype to
      gastric cancer cells through transactivation of SIRT1 expression.
AB  - BACKGROUND: Multidrug resistance (MDR) in gastric cancer remains a major
      challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a
      stress response gene involved in homeostasis and cellular protection. However,
      the expression and function of ATF4 in gastric cancer MDR remains unknown. In
      this study, we investigate whether ATF4 play a role in gastric cancer MDR and its
      potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4
      overexpression confered the MDR phenotype to gastric cancer cells, while
      knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we
      also showed that the NAD(+)-dependent histone deacetylase SIRT1 was required for
      ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4
      facilitated MDR in gastric cancer cells through direct binding to the SIRT1
      promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by
      small interfering RNA (siRNA) or a specific inhibitor (EX-527) reintroduced
      therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression
      level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We
      showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells
      in response to chemotherapy and these findings suggest that targeting ATF4 could
      relieve therapeutic resistance in gastric cancer.

PMID- 22363647
TI  - Verticillium longisporum infection affects the leaf apoplastic proteome,
      metabolome, and cell wall properties in Arabidopsis thaliana.
AB  - Verticillium longisporum (VL) is one of the most devastating diseases in
      important oil crops from the family of Brassicaceae. The fungus resides for much
      time of its life cycle in the extracellular fluid of the vascular system, where
      it cannot be controlled by conventional fungicides. To obtain insights into the
      biology of VL-plant interaction in the apoplast, the secretome consisting of the
      extracellular proteome and metabolome as well as cell wall properties were
      studied in the model Brassicaceae, Arabidopsis thaliana. VL infection resulted in
      increased production of cell wall material with an altered composition of
      carbohydrate polymers and increased lignification. The abundance of several
      hundred soluble metabolites changed in the apoplast of VL-infected plants
      including signalling and defence compounds such as glycosides of salicylic acid,
      lignans and dihydroxybenzoic acid as well as oxylipins. The extracellular
      proteome of healthy leaves was enriched in antifungal proteins. VL caused
      specific increases in six apoplast proteins (three peroxidases PRX52, PRX34, P37,
      serine carboxypeptidase SCPL20, alpha-galactosidase AGAL2 and a germin-like
      protein GLP3), which have functions in defence and cell wall modification. The
      abundance of a lectin-like, chitin-inducible protein (CILLP) was reduced. Since
      the transcript levels of most of the induced proteins were not elevated until
      late infection time points (>20 dpi), whereas those of CILLP and GLP3 were
      reduced at earlier time points, our results may suggest that VL enhances its
      virulence by rapid down-regulation and delay of induction of plant defence genes.

PMID- 22363648
TI  - Accelerated identification of proteins by mass spectrometry by employing covalent
      pre-gel staining with Uniblue A.
AB  - BACKGROUND: The identification of proteins by mass spectrometry is a standard
      method in biopharmaceutical quality control and biochemical research. Prior to
      identification by mass spectrometry, proteins are usually pre-separated by
      electrophoresis. However, current protein staining and de-staining protocols are
      tedious and time consuming, and therefore prolong the sample preparation time for
      mass spectrometry. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a 1-minute
      covalent pre-gel staining protocol for proteins, which does not require de
      staining before the mass spectrometry analysis. We investigated the
      electrophoretic properties of derivatized proteins and peptides and studied their
      behavior in mass spectrometry. Further, we elucidated the preferred reaction of
      proteins with Uniblue A and demonstrate the integration of the peptide
      derivatization into typical informatics tools. CONCLUSIONS AND SIGNIFICANCE: The
      Uniblue A staining method drastically speeds up the sample preparation for the
      mass spectrometry based identification of proteins. The application of this chemo
      proteomic strategy will be advantageous for routine quality control of proteins
      and for time-critical tasks in protein analysis.

PMID- 22363649
TI  - Cardiac signatures of personality.
AB  - BACKGROUND: There are well-established relations between personality and the
      heart, as evidenced by associations between negative emotions on the one hand,
      and coronary heart disease or chronic heart failure on the other. However, there
      are substantial gaps in our knowledge about relations between the heart and
      personality in healthy individuals. Here, we investigated whether amplitude
      patterns of the electrocardiogram (ECG) correlate with neurotisicm, extraversion,
      agreeableness, warmth, positive emotion, and tender-mindedness as measured with
      the Neuroticism-Extraversion-Openness (NEO) personality inventory. Specifically,
      we investigated (a) whether a cardiac amplitude measure that was previously
      reported to be related to flattened affectivity (referred to as Ekappa values)
      would explain variance of NEO scores, and (b) whether correlations can be found
      between NEO scores and amplitudes of the ECG. METHODOLOGY/PRINCIPAL FINDINGS: NEO
      scores and rest ECGs were obtained from 425 healthy individuals. Neuroticism and
      positive emotion significantly differed between individuals with high and low
      Ekappa values. In addition, stepwise cross-validated regressions indicated
      correlations between ECG amplitudes and (a) agreeableness, as well as (b)
      positive emotion. CONCLUSIONS/SIGNIFICANCE: These results are the first to
      demonstrate that ECG amplitude patterns provide information about the personality
      of an individual as measured with NEO personality scales and facets. These
      findings open new perspectives for a more efficient personality assessment using
      cardiac measures, as well as for more efficient risk-stratification and pre
      clinical diagnosis of individuals at risk for cardiac, affective and
      psychosomatic disorders.

PMID- 22363650
TI  - Infectivity in skeletal muscle of cattle with atypical bovine spongiform
      encephalopathy.
AB  - The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is
      caused by a prion strain whose biological properties differ from those of typical
      BSE, resulting in a clinically and pathologically distinct phenotype. Whether
      peripheral tissues of BASE-affected cattle contain infectivity is unknown. This
      is a critical issue since the BASE prion is readily transmissible to a variety of
      hosts including primates, suggesting that humans may be susceptible. We carried
      out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found
      infectivity in a variety of skeletal muscles from cattle with natural and
      experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted
      disease, although the attack rate differed between experimental and natural cases
      (~70% versus ~10%, respectively). This difference was likely related to different
      prion titers, possibly due to different stages of disease in the two conditions,
      i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural
      BASE. The neuropathological phenotype and PrP(res) type were consistent in all
      affected mice and matched those of Tgbov XV mice infected with brain homogenate
      from natural BASE. The immunohistochemical analysis of skeletal muscles from
      cattle with natural and experimental BASE showed the presence of abnormal prion
      protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with
      lymphoid tissue and kidney from natural and experimental BASE did not develop
      disease. The novel information on the neuromuscular tropism of the BASE strain,
      efficiently overcoming species barriers, underlines the relevance of maintaining
      an active surveillance.

PMID- 22363651
TI  - Economic games on the internet: the effect of $1 stakes.
AB  - Online labor markets such as Amazon Mechanical Turk (MTurk) offer an
      unprecedented opportunity to run economic game experiments quickly and
      inexpensively. Using Mturk, we recruited 756 subjects and examined their behavior
      in four canonical economic games, with two payoff conditions each: a stakes
      condition, in which subjects' earnings were based on the outcome of the game
      (maximum earnings of $1); and a no-stakes condition, in which subjects' earnings
      are unaffected by the outcome of the game. Our results demonstrate that economic
      game experiments run on MTurk are comparable to those run in laboratory settings,
      even when using very low stakes.

PMID- 22363652
TI  - Ghrelin indirectly activates hypophysiotropic CRF neurons in rodents.
AB  - Ghrelin is a stomach-derived hormone that regulates food intake and
      neuroendocrine function by acting on its receptor, GHSR (Growth Hormone
      Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin
      is to signal stress to the brain. It has been suggested that one of the potential
      stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)
      producing neurons of the hypothalamic paraventricular nucleus, which secrete the
      CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary
      adrenal axis. However, the neural circuits that mediate the ghrelin-induced
      activation of this neuroendocrine axis are mostly uncharacterized. In the current
      study, we characterized in vivo the mechanism by which ghrelin activates the
      hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro
      ventricular administration of ghrelin strongly activates c-fos--a marker of
      cellular activation--in CRF-producing neurons. Also, ghrelin activates CRF gene
      expression in the paraventricular nucleus of the hypothalamus and the
      hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration
      directly into the paraventricular nucleus of the hypothalamus also induces c-fos
      within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis,
      without any significant effect on the food intake. Interestingly, dual-label
      immunohistochemical analysis and ghrelin binding studies failed to show GHSR
      expression in CRF neurons. Thus, we conclude that ghrelin activates
      hypophysiotropic CRF neurons, albeit indirectly.

PMID- 22363653
TI  - Effects of male hypogonadism on regional adipose tissue fatty acid storage and
      lipogenic proteins.
AB  - Testosterone has long been known to affect body fat distribution, although the
      underlying mechanisms remain elusive. We investigated the effects of chronic
      hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage
      factors. Twelve men with chronic hypogonadism and 13 control men matched for age
      and body composition: 1) underwent measures of body composition with dual energy
      x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal
      containing [(3)H]triolein to determine the fate of meal FA (biopsy-measured
      adipose storage vs. oxidation); 3) received infusions of [U-(13)C]palmitate and
      [1-(14)C]palmitate to measure rates of direct free (F)FA storage (adipose
      biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and
      diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content
      were measured to understand the mechanism by which alterations in fat storage
      occur in response to testosterone deficiency. Results of the study showed that
      hypogonadal men stored a greater proportion of both dietary FA and FFA in lower
      body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose
      tissue ACS activity was significantly greater in hypogonadal than eugonadal men,
      whereas CD36 and DGAT were not different between the two groups. The
      relationships between these proteins and FA storage varied somewhat between the
      two groups. We conclude that chronic effects of testosterone deficiency has
      effects on leg adipose tissue ACS activity which may relate to greater lower body
      FA storage. These results provide further insight into the role of androgens in
      body fat distribution and adipose tissue metabolism in humans.

PMID- 22363654
TI  - LAL regulators SCO0877 and SCO7173 as pleiotropic modulators of phosphate
      starvation response and actinorhodin biosynthesis in Streptomyces coelicolor.
AB  - LAL regulators (Large ATP-binding regulators of the LuxR family) constitute a
      poorly studied family of transcriptional regulators. Several regulators of this
      class have been identified in antibiotic and other secondary metabolite gene
      clusters from actinomycetes, thus they have been considered pathway-specific
      regulators. In this study we have obtained two disruption mutants of LAL genes
      from S. coelicolor (Delta0877 and Delta7173). Both mutants were deficient in the
      production of the polyketide antibiotic actinorhodin, and antibiotic production
      was restored upon gene complementation of the mutants. The use of whole-genome
      DNA microarrays and quantitative PCRs enabled the analysis of the transcriptome
      of both mutants in comparison with the wild type. Our results indicate that the
      LAL regulators under study act globally affecting various cellular processes, and
      amongst them the phosphate starvation response and the biosynthesis of the blue
      pigmented antibiotic actinorhodin. Both regulators act as negative modulators of
      the expression of the two-component phoRP system and as positive regulators of
      actinorhodin biosynthesis. To our knowledge this is the first characterization of
      LAL regulators with wide implications in Streptomyces metabolism.

PMID- 22363655
TI  - Sox10 controls migration of B16F10 melanoma cells through multiple regulatory
      target genes.
AB  - It is believed that the inherent differentiation program of melanocytes during
      embryogenesis predisposes melanoma cells to high frequency of metastasis. Sox10,
      a transcription factor expressed in neural crest stem cells and a subset of
      progeny lineages, plays a key role in the development of melanocytes. We show
      that B16F10 melanoma cells transfected with siRNAs specific for Sox10 display
      reduced migratory activity which in turn indicated that a subset of
      transcriptional regulatory target genes of Sox10 is likely to be involved in
      migration and metastasis of melanoma cells. We carried out a microarray-based
      gene expression profiling using a Sox10-specific siRNA to identify relevant
      regulatory targets and found that multiple genes including melanocortin-1
      receptor (Mc1r) partake in the regulation of migration. We provide evidences that
      the effect of Sox10 on migration is mediated in large part by Mitf, a
      transcription factor downstream to Sox10. Among the mouse melanoma cell lines
      examined, however, only B16F10 showed robust down-regulation of Sox10 and
      inhibition of cell migration indicating that further dissection of dosage effects
      and/or cell line-specific regulatory networks is necessary. The involvement of
      Mc1r in migration was studied in detail in vivo using a murine metastasis model.
      Specifically, B16F10 melanoma cells treated with a specific siRNA showed reduced
      tendency in metastasizing to and colonizing the lung after being injected in the
      tail vein. These data reveal a cadre of novel regulators and mediators involved
      in migration and metastasis of melanoma cells that represents potential targets
      of therapeutic intervention.

PMID- 22363656
TI  - There's something about a fair split: intentionality moderates context-based
      fairness considerations in social decision-making.
AB  - Fairness considerations are a strong motivational force in social decision
      making. Here, we investigated the role of intentionality in response to unfair
      offers in the Ultimatum Game by manipulating both proposers' degree of control
      over the selection of offers and the context pertaining to the outcomes of offers
      proposers can choose from. As a result, the design enabled us to disentangle
      intention- and context-based decision-making processes. Rejection rates were
      higher when an unfair offer was intentionally chosen over a fair alternative than
      when it was chosen by the computer, outside proposers' control. This finding
      provides direct evidence for intention-based decision-making. Also, rejection
      rates in general were sensitive to the context in which an offer was made,
      indicating the involvement of both intention- and context-based processes in
      social decision-making. Importantly, however, the current study highlights the
      role of intention-based fairness considerations in basic decision-making
      situations where outcomes are explicitly stated and thus easy to compare. Based
      on these results, we propose that fairness can be judged on different, but
      additive levels of (social-) cognitive processing that might have different
      developmental trajectories.

PMID- 22363659
TI  - Contrast in edge vegetation structure modifies the predation risk of natural
      ground nests in an agricultural landscape.
AB  - Nest predation risk generally increases nearer forest-field edges in agricultural
      landscapes. However, few studies test whether differences in edge contrast (i.e.
      hard versus soft edges based on vegetation structure and height) affect edge
      related predation patterns and if such patterns are related to changes in nest
      conspicuousness between incubation and nestling feeding. Using data on 923
      nesting attempts we analyse factors influencing nest predation risk at different
      edge types in an agricultural landscape of a ground-cavity breeding bird species,
      the Northern Wheatear (Oenanthe oenanthe). As for many other bird species, nest
      predation is a major determinant of reproductive success in this migratory
      passerine. Nest predation risk was higher closer to woodland and crop field
      edges, but only when these were hard edges in terms of ground vegetation
      structure (clear contrast between tall vs short ground vegetation). No such edge
      effect was observed at soft edges where adjacent habitats had tall ground
      vegetation (crop, ungrazed grassland). This edge effect on nest predation risk
      was evident during the incubation stage but not the nestling feeding stage. Since
      wheatear nests are depredated by ground-living animals our results demonstrate:
      (i) that edge effects depend on edge contrast, (ii) that edge-related nest
      predation patterns vary across the breeding period probably resulting from
      changes in parental activity at the nest between the incubation and nestling
      feeding stage. Edge effects should be put in the context of the nest predator
      community as illustrated by the elevated nest predation risk at hard but not soft
      habitat edges when an edge is defined in terms of ground vegetation. These
      results thus can potentially explain previously observed variations in edge
      related nest predation risk.

PMID- 22363657
TI  - RHGF-2 is an essential Rho-1 specific RhoGEF that binds to the multi-PDZ domain
      scaffold protein MPZ-1 in Caenorhabditis elegans.
AB  - RhoGEF proteins activate the Rho family of small GTPases and thus play a key role
      in regulating fundamental cellular processes such as cell morphology and
      polarity, cell cycle progression and gene transcription. We identified a
      Caenorhabditis elegans RhoGEF protein, RHGF-2, as a binding partner of the C.
      elegans multi-PDZ domain scaffold protein MPZ-1 (MUPP1 in mammals). RHGF-2
      exhibits significant identity to the mammalian RhoGEFs PLEKHG5/Tech/Syx and
      contains a class I C-terminal PDZ binding motif (SDV) that interacts most
      strongly to MPZ-1 PDZ domain eight. RHGF-2 RhoGEF activity is specific to the C.
      elegans RhoA homolog RHO-1 as determined by direct binding, GDP/GTP exchange and
      serum response element-driven reporter activity. rhgf-2 is an essential gene
      since rhgf-2 deletion mutants do not elongate during embryogenesis and hatch as
      short immobile animals that arrest development. Interestingly, the expression of
      a functional rhgf-2::gfp transgene appears to be exclusively neuronal and rhgf-2
      overexpression results in loopy movement with exaggerated body bends. Transient
      expression of RHGF-2 in N1E-115 neuroblastoma cells prevents neurite outgrowth
      similar to constitutive RhoA activation in these cells. Together, these
      observations indicate neuronally expressed RHGF-2 is an essential RHO-1 specific
      RhoGEF that binds most strongly to MPZ-1 PDZ domain eight and is required for
      wild-type C. elegans morphology and growth.

PMID- 22363658
TI  - DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts
      clinical outcome in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers
      worldwide. To identify biologically relevant genes with prognostic and
      therapeutic significance in PDAC, we first performed the microarray gene
      expression profiling in 45 matching pairs of tumor and adjacent non-tumor tissues
      from resected PDAC cases. We identified 36 genes that were associated with
      patient outcome and also differentially expressed in tumors as compared with
      adjacent non-tumor tissues in microarray analysis. Further evaluation in an
      independent validation cohort (N = 27) confirmed that DPEP1 (dipeptidase 1)
      expression was decreased (T:N ratio ~0.1, P<0.01) in tumors as compared with non
      tumor tissues. DPEP1 gene expression was negatively correlated with histological
      grade (Spearman correlation coefficient = -0.35, P = 0.004). Lower expression of
      DPEP1 in tumors was associated with poor survival (Kaplan Meier log rank) in both
      test cohort (P = 0.035) and validation cohort (P = 0.016). DPEP1 expression was
      independently associated with cancer-specific mortality when adjusted for tumor
      stage and resection margin status in both univariate (hazard ratio = 0.43, 95%CI
      = 0.24-0.76, P = 0.004) and multivariate analyses (hazard ratio = 0.51, 95%CI =
      0.27-0.94, P = 0.032). We further demonstrated that overexpression of DPEP1
      suppressed tumor cells invasiveness and increased sensitivity to chemotherapeutic
      agent Gemcitabine. Our data also showed that growth factor EGF treatment
      decreased DPEP1 expression and MEK1/2 inhibitor AZD6244 increased DPEP1
      expression in vitro, indicating a potential mechanism for DPEP1 gene regulation.
      Therefore, we provide evidence that DPEP1 plays a role in pancreatic cancer
      aggressiveness and predicts outcome in patients with resected PDAC. In view of
      these findings, we propose that DPEP1 may be a candidate target in PDAC for
      designing improved treatments.

PMID- 22363660
TI  - Effects of vegetation, corridor width and regional land use on early successional
      birds on powerline corridors.
AB  - Powerline rights-of-way (ROWs) often provide habitat for early successional bird
      species that have suffered long-term population declines in eastern North
      America. To determine how the abundance of shrubland birds varies with habitat
      within ROW corridors and with land use patterns surrounding corridors, we ran
      Poisson regression models on data from 93 plots on ROWs and compared regression
      coefficients. We also determined nest success rates on a 1-km stretch of ROW.
      Seven species of shrubland birds were common in powerline corridors. However, the
      nest success rates for prairie warbler (Dendroica discolor) and field sparrow
      (Spizella pusilla) were <21%, which is too low to compensate for estimated annual
      mortality. Some shrubland bird species were more abundant on narrower ROWs or at
      sites with lower vegetation or particular types of vegetation, indicating that
      vegetation management could be refined to favor species of high conservation
      priority. Also, several species were more abundant in ROWs traversing
      unfragmented forest than those near residential areas or farmland, indicating
      that corridors in heavily forested regions may provide better habitat for these
      species. In the area where we monitored nests, brood parasitism by brown-headed
      cowbirds (Molothrus ater) occurred more frequently close to a residential area.
      Although ROWs support dense populations of shrubland birds, those in more heavily
      developed landscapes may constitute sink habitat. ROWs in extensive forests may
      contribute more to sustaining populations of early successional birds, and thus
      may be the best targets for habitat management.

PMID- 22363662
TI  - Does hepatitis C virus infection increase risk for stroke? A population-based
      cohort study.
AB  - BACKGROUND: The relationship between hepatitis C virus infection and risk of
      stroke remains inconsistent. This study evaluates the risk of stroke in
      association with chronic hepatitis C infection in a longitudinal population-based
      cohort. METHODS: We identified 4,094 adults newly diagnosed with hepatitis C
      infection in 2002-2004 from the Taiwan National Health Insurance Research
      Database. Comparison group consisted of 16,376 adults without hepatitis C
      infection randomly selected from the same dataset, frequency matched by age and
      sex. Events of stroke from 2002-2008 were ascertained from medical claims
      (International Classification of Diseases, Ninth Revision, Clinical Modification,
      ICD-9-CM, codes 430-438). Multivariate adjusted hazard ratios (HRs) and 95%
      confidence intervals (CIs) were estimated for potential associated factors
      including HCV infection, age, sex, low-income status, urbanization, cessation of
      cigarette smoking, alcohol-related illness, obesity, history of chronic diseases
      and medication use. FINDINGS: During 96,752 person-years of follow-up, there were
      1981 newly diagnosed stroke cases. The HRs of stroke associated with medical
      conditions such as hypertension, diabetes and heart disease were 1.48 (95% CI
      1.33 to 1.65), 1.23 (95% CI 1.11 to 1.36) and 1.17 (95% CI 1.06 to 1.30),
      respectively, after adjustment for covariates. The cumulative risk of stroke for
      people with hepatitis C and without hepatitis C infections was 2.5% and 1.9%,
      respectively (p<0.0001). Compared with people without hepatitis C infection, the
      adjusted HR of stroke was 1.27 (95% CI 1.14 to 1.41) for people with hepatitis C
      infection. CONCLUSION: Chronic hepatitis C infection increases stroke risk and
      should be considered an important and independent risk factor.

PMID- 22363661
TI  - Contribution of an aged microenvironment to aging-associated myeloproliferative
      disease.
AB  - The molecular and cellular mechanisms of the age-associated increase in the
      incidence of acute myeloid leukemia (AML) remain poorly understood. Multiple
      studies support that the bone marrow (BM) microenvironment has an important
      influence on leukemia progression. Given that the BM niche itself undergoes
      extensive functional changes during lifetime, we hypothesized that one mechanism
      for the age-associated increase in leukemia incidence might be that an aged niche
      promotes leukemia progression. The most frequent genetic alteration in AML is the
      t(8;21) translocation, resulting in the expression of the AML1-ETO fusion
      protein. Expression of the fusion protein in hematopoietic cells results in mice
      in a myeloproliferative disorder. Testing the role of the age of the niche on
      leukemia progression, we performed both transplantation and in vitro co-culture
      experiments. Aged animals transplanted with AML1-ETO positive HSCs presented with
      a significant increase in the frequency of AML-ETO positive early progenitor
      cells in BM as well as an increased immature myeloid cell load in blood compared
      to young recipients. These findings suggest that an aged BM microenvironment
      allows a relative better expansion of pre-leukemic stem and immature myeloid
      cells and thus imply that the aged microenvironment plays a role in the elevated
      incidence of age-associated leukemia.

PMID- 22363664
TI  - Discovery of intramolecular signal transduction network based on a new protein
      dynamics model of energy dissipation.
AB  - A novel approach to reveal intramolecular signal transduction network is proposed
      in this work. To this end, a new algorithm of network construction is developed,
      which is based on a new protein dynamics model of energy dissipation. A key
      feature of this approach is that direction information is specified after
      inferring protein residue-residue interaction network involved in the process of
      signal transduction. This enables fundamental analysis of the regulation
      hierarchy and identification of regulation hubs of the signaling network. A well
      studied allosteric enzyme, E. coli aspartokinase III, is used as a model system
      to demonstrate the new method. Comparison with experimental results shows that
      the new approach is able to predict all the sites that have been experimentally
      proved to desensitize allosteric regulation of the enzyme. In addition, the
      signal transduction network shows a clear preference for specific structural
      regions, secondary structural types and residue conservation. Occurrence of super
      hubs in the network indicates that allosteric regulation tends to gather residues
      with high connection ability to collectively facilitate the signaling process.
      Furthermore, a new parameter of propagation coefficient is defined to determine
      the propagation capability of residues within a signal transduction network. In
      conclusion, the new approach is useful for fundamental understanding of the
      process of intramolecular signal transduction and thus has significant impact on
      rational design of novel allosteric proteins.

PMID- 22363663
TI  - New insight into the transcarbamylase family: the structure of putrescine
      transcarbamylase, a key catalyst for fermentative utilization of agmatine.
AB  - Transcarbamylases reversibly transfer a carbamyl group from carbamylphosphate
      (CP) to an amine. Although aspartate transcarbamylase and ornithine
      transcarbamylase (OTC) are well characterized, little was known about putrescine
      transcarbamylase (PTC), the enzyme that generates CP for ATP production in the
      fermentative catabolism of agmatine. We demonstrate that PTC (from Enterococcus
      faecalis), in addition to using putrescine, can utilize L-ornithine as a poor
      substrate. Crystal structures at 2.5 A and 2.0 A resolutions of PTC bound to its
      respective bisubstrate analog inhibitors for putrescine and ornithine use, N
      (phosphonoacetyl)-putrescine and delta-N-(phosphonoacetyl)-L-ornithine, shed
      light on PTC preference for putrescine. Except for a highly prominent C-terminal
      helix that projects away and embraces an adjacent subunit, PTC closely resembles
      OTCs, suggesting recent divergence of the two enzymes. Since differences between
      the respective 230 and SMG loops of PTC and OTC appeared to account for the
      differential preference of these enzymes for putrescine and ornithine, we
      engineered the 230-loop of PTC to make it to resemble the SMG loop of OTCs,
      increasing the activity with ornithine and greatly decreasing the activity with
      putrescine. We also examined the role of the C-terminal helix that appears a
      constant and exclusive PTC trait. The enzyme lacking this helix remained active
      but the PTC trimer stability appeared decreased, since some of the enzyme eluted
      as monomers from a gel filtration column. In addition, truncated PTC tended to
      aggregate to hexamers, as shown both chromatographically and by X-ray
      crystallography. Therefore, the extra C-terminal helix plays a dual role: it
      stabilizes the PTC trimer and, by shielding helix 1 of an adjacent subunit, it
      prevents the supratrimeric oligomerizations of obscure significance observed with
      some OTCs. Guided by the structural data we identify signature traits that permit
      easy and unambiguous annotation of PTC sequences.

PMID- 22363666
TI  - Molecular evolution of the deuterolysin (M35) family genes in Coccidioides.
AB  - Coccidioides is a primary fungal pathogen of humans, causing life-threatening
      respiratory disease known as coccidioidomycosis (Valley fever) in
      immunocompromised individuals. Recently, Sharpton et al (2009) found that the
      deuterolysin (M35) family genes were significantly expanded in both the
      Coccidioides genus and in U. reesii, and that Coccidioides has acquired three
      more M35 family genes than U. reesii. In the present work, phylogenetic analyses
      based on a total of 28 M35 family genes using different alignments and tree
      building methods consistently revealed five clades with high nodal supports.
      Interestingly, likelihood ratio tests suggested significant differences in
      selective pressure on the ancestral lineage of three additional duplicated M35
      family genes from Coccidioides species compared to the other lineages in the
      phylogeny, which may be associated with novel functional adaptations of M35
      family genes in the Coccidioides species, e.g., recent pathogenesis acquisition.
      Our study adds to the expanding view of M35 family gene evolution and functions
      as well as establishes a theoretical foundation for future experimental
      investigations.

PMID- 22363665
TI  - Severe pandemic H1N1 2009 infection is associated with transient NK and T
      deficiency and aberrant CD8 responses.
AB  - BACKGROUND: It is unclear why the severity of influenza varies in healthy adults
      or why the burden of severe influenza shifts to young adults when pandemic
      strains emerge. One possibility is that cross-protective T cell responses wane in
      this age group in the absence of recent infection. We therefore compared the
      acute cellular immune response in previously healthy adults with severe versus
      mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously
      healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam
      with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39
      recovered quickly whereas 10 developed severe symptoms requiring supplemental
      oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts
      and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression
      were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8
      lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001),
      28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized
      following recovery. B cell counts were not significantly associated with
      severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6
      22%) were HLADR+CD38+, and was accompanied by a significant loss of
      resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells.
      In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was
      excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28-
      cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated
      with transient T and NK cell deficiency. CD8 phenotype changes during mild
      influenza are consistent with a rapidly resolving memory response whereas in
      severe influenza activation is either delayed or excessive, and partially
      differentiated cells accumulate within blood indicating that recruitment of
      effector cells to the lung could be impaired.

PMID- 22363667
TI  - MLVA subtyping of genovar E Chlamydia trachomatis individualizes the Swedish
      variant and anorectal isolates from men who have sex with men.
AB  - This study describes a new multilocus variable number tandem-repeat (VNTR)
      analysis (MLVA) typing system for the discrimination of Chlamydia trachomatis
      genovar D to K isolates or specimens. We focused our MLVA scheme on genovar E
      which predominates in most populations worldwide. This system does not require
      culture and therefore can be performed directly on DNA extracted from positive
      clinical specimens. Our method was based on GeneScan analysis of five VNTR loci
      labelled with fluorescent dyes by multiplex PCR and capillary electrophoresis.
      This MLVA, called MLVA-5, was applied to a collection of 220 genovar E and 94 non
      E genovar C. trachomatis isolates and specimens obtained from 251 patients and
      resulted in 38 MLVA-5 types. The genetic stability of the MLVA-5 scheme was
      assessed for results obtained both in vitro by serial passage culturing and in
      vivo using concomitant and sequential isolates and specimens. All anorectal
      genovar E isolates from men who have sex with men exhibited the same MLVA-5 type,
      suggesting clonal spread. In the same way, we confirmed the clonal origin of the
      Swedish new variant of C. trachomatis. The MLVA-5 assay was compared to three
      other molecular typing methods, ompA gene sequencing, multilocus sequence typing
      (MLST) and a previous MLVA method called MLVA-3, on 43 genovar E isolates. The
      discriminatory index was 0.913 for MLVA-5, 0.860 for MLST and 0.622 for MLVA-3.
      Among all of these genotyping methods, MLVA-5 displayed the highest
      discriminatory power and does not require a time-consuming sequencing step. The
      results indicate that MLVA-5 enables high-resolution molecular epidemiological
      characterisation of C. trachomatis genovars D to K infections directly from
      specimens.

PMID- 22363668
TI  - The rph1 gene is a common contributor to the evolution of phosphine resistance in
      independent field isolates of Rhyzopertha dominica.
AB  - Phosphine is the only economically viable fumigant for routine control of insect
      pests of stored food products, but its continued use is now threatened by the
      world-wide emergence of high-level resistance in key pest species. Phosphine has
      a unique mode of action relative to well-characterised contact pesticides.
      Similarly, the selective pressures that lead to resistance against field sprays
      differ dramatically from those encountered during fumigation. The consequences of
      these differences have not been investigated adequately. We determine the genetic
      basis of phosphine resistance in Rhyzopertha dominica strains collected from New
      South Wales and South Australia and compare this with resistance in a previously
      characterised strain from Queensland. The resistance levels range from 225 and
      100 times the baseline response of a sensitive reference strain. Moreover,
      molecular and phenotypic data indicate that high-level resistance was derived
      independently in each of the three widely separated geographical regions. Despite
      the independent origins, resistance was due to two interacting genes in each
      instance. Furthermore, complementation analysis reveals that all three strains
      contain an incompletely recessive resistance allele of the autosomal rph1
      resistance gene. This is particularly noteworthy as a resistance allele at rph1
      was previously proposed to be a necessary first step in the evolution of high
      level resistance. Despite the capacity of phosphine to disrupt a wide range of
      enzymes and biological processes, it is remarkable that the initial step in the
      selection of resistance is so similar in isolated outbreaks.

PMID- 22363669
TI  - Long-range temporal correlations in the EEG bursts of human preterm babies.
AB  - The electrical activity in the very early human preterm brain, as recorded by
      scalp EEG, is mostly discontinuous and has bursts of high-frequency oscillatory
      activity nested within slow-wave depolarisations of high amplitude. The temporal
      organisation of the occurrence of these EEG bursts has not been previously
      investigated. We analysed the distribution of the EEG bursts in 11 very preterm
      (23-30 weeks gestational age) human babies through two estimates of the Hurst
      exponent. We found long-range temporal correlations (LRTCs) in the occurrence of
      these EEG bursts demonstrating that even in the very immature human brain, when
      the cerebral cortical structure is far from fully developed, there is non-trivial
      temporal structuring of electrical activity.

PMID- 22363670
TI  - Fire history from life-history: determining the fire regime that a plant
      community is adapted using life-histories.
AB  - Wildfire is a fundamental disturbance process in many ecological communities, and
      is critical in maintaining the structure of some plant communities. In the past
      century, changes in global land use practices have led to changes in fire regimes
      that have radically altered the composition of many plant communities. As the
      severe biodiversity impacts of inappropriate fire management regimes are
      recognized, attempts are being made to manage fires within a more 'natural'
      regime. In this aim, the focus has typically been on determining the fire regime
      to which the community has adapted. Here we take a subtly different approach and
      focus on the probability of a patch being burnt. We hypothesize that competing
      sympatric taxa from different plant functional groups are able to coexist due to
      the stochasticity of the fire regime, which creates opportunities in both time
      and space that are exploited differentially by each group. We exploit this
      situation to find the fire probability at which three sympatric grasses, from
      different functional groups, are able to co-exist. We do this by parameterizing a
      spatio-temporal simulation model with the life-history strategies of the three
      species and then search for the fire frequency and scale at which they are able
      to coexist when in competition. The simulation gives a clear result that these
      species only coexist across a very narrow range of fire probabilities centred at
      0.2. Conversely, fire scale was found only to be important at very large scales.
      Our work demonstrates the efficacy of using competing sympatric species with
      different regeneration niches to determine the probability of fire in any given
      patch. Estimating this probability allows us to construct an expected historical
      distribution of fire return intervals for the community; a critical resource for
      managing fire-driven biodiversity in the face of a growing carbon economy and
      ongoing climate change.

PMID- 22363671
TI  - Reduced proliferation in the adult mouse subventricular zone increases survival
      of olfactory bulb interneurons.
AB  - Neurogenesis in the adult brain is largely restricted to the subependymal zone
      (SVZ) of the lateral ventricle, olfactory bulb (OB) and the dentate subgranular
      zone, and survival of adult-born cells in the OB is influenced by factors
      including sensory experience. We examined, in mice, whether survival of adult
      born cells is also regulated by the rate of precursor proliferation in the SVZ.
      Precursor proliferation was decreased by depleting the SVZ of dopamine after
      lesioning dopamine neurons in the substantia nigra compacta with 6
      hydroxydopamine. Subsequently, we examined the effect of reduced SVZ
      proliferation on the generation, migration and survival of neuroblasts and mature
      adult-born cells in the SVZ, rostral migratory stream (RMS) and OB. Proliferating
      cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU) injected 2 hours
      prior to death or by immunoreactivity against Ki67, were reduced by 47% or 36%,
      respectively, 7 days after dopamine depletion, and by 29% or 31% 42 days after
      dopamine depletion, compared to sham-treated animals. Neuroblast generation in
      the SVZ and their migration along the RMS were not affected, neither 7 nor 42
      days after the 6-hydroxydopamine injection, since the number of doublecortin
      immunoreactive neuroblasts in the SVZ and RMS, as well as the number of neuronal
      nuclei-immunoreactive cells in the OB, were stable compared to control. However,
      survival analysis 15 days after 6-hydroxydopamine and 6 days after BrdU
      injections showed that the number of BrdU+ cells in the SVZ was 70% higher. Also,
      42 days after 6-hydroxydopamine and 30 days after BrdU injections, we found an
      82% increase in co-labeled BrdU+/gamma-aminobutyric acid-immunoreactive cell
      bodies in the granular cell layer, while double-labeled BrdU+/tyrosine
      hydroxylase-immunoreactive cell bodies in the glomerular layer increased by 148%.
      We conclude that the number of OB interneurons following reduced SVZ
      proliferation is maintained through an increased survival of adult-born precursor
      cells, neuroblasts and interneurons.

PMID- 22363672
TI  - The use of automated quantitative analysis to evaluate epithelial-to-mesenchymal
      transition associated proteins in clear cell renal cell carcinoma.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has recently been
      implicated in the initiation and progression of renal cell carcinoma (RCC). Some
      mRNA gene expression studies have suggested a link between the EMT phenotype and
      poorer clinical outcome from RCC. This study evaluated expression of EMT
      associated proteins in RCC using in situ automated quantitative analysis
      immunofluorescence (AQUA) and compared expression levels with clinical outcome.
      METHODS/PRINCIPAL FINDINGS: Unsupervised hierarchical cluster analysis of pre
      existing RCC gene expression array data (GSE16449) from 36 patients revealed the
      presence of an EMT transcriptional signature in RCC [E-cadherin high/SLUG
      low/SNAIL low]. As automated immunofluorescence technology is dependent on
      accurate definition of the tumour cells in which measurements take place is
      critical, extensive optimisation was carried out resulting in a novel pan
      cadherin based tumour mask that distinguishes renal cancer cells from stromal
      components. 61 patients with ccRCC and clinical follow-up were subsequently
      assessed for expression of EMT-associated proteins (WT1, SNAIL, SLUG, E-cadherin
      and phospho-beta-catenin) on tissue microarrays. Using Kaplan-Meier analysis both
      SLUG (p = 0.029) and SNAIL (p = 0.024) (log rank Mantel-Cox) were significantly
      associated with prolonged progression free survival (PFS). Using Cox regression
      univariate and multivariate analysis none of the biomarkers were significantly
      correlated with outcome. 14 of the 61 patients expressed the gene expression
      analysis predicted EMT-protein signature [E-cadherin high/SLUG low/SNAIL low],
      which was not found to be associated to PFS when measured at the protein level. A
      combination of high expression of SNAIL and low stage was able to stratify
      patients with greater significance (p = 0.001) then either variable alone (high
      SNAIL p = 0.024, low stage p = 0.029). CONCLUSIONS: AQUA has been shown to have
      the potential to identify EMT related protein targets in RCC allowing for
      stratification of patients into high and low risk groups, as well the ability to
      assess the association of reputed EMT signatures to progression of the disease.

PMID- 22363674
TI  - Proteomic identification of S-nitrosylated Golgi proteins: new insights into
      endothelial cell regulation by eNOS-derived NO.
AB  - BACKGROUND: Endothelial nitric oxide synthase (eNOS) is primarily localized on
      the Golgi apparatus and plasma membrane caveolae in endothelial cells.
      Previously, we demonstrated that protein S-nitrosylation occurs preferentially
      where eNOS is localized. Thus, in endothelial cells, Golgi proteins are likely to
      be targets for S-nitrosylation. The aim of this study was to identify S
      nitrosylated Golgi proteins and attribute their S-nitrosylation to eNOS-derived
      nitric oxide in endothelial cells. METHODS: Golgi membranes were isolated from
      rat livers. S-nitrosylated Golgi proteins were determined by a modified biotin
      switch assay coupled with mass spectrometry that allows the identification of the
      S-nitrosylated cysteine residue. The biotin switch assay followed by Western blot
      or immunoprecipitation using an S-nitrosocysteine antibody was also employed to
      validate S-nitrosylated proteins in endothelial cell lysates. RESULTS: Seventy
      eight potential S-nitrosylated proteins and their target cysteine residues for S
      nitrosylation were identified; 9 of them were Golgi-resident or Golgi/endoplasmic
      reticulum (ER)-associated proteins. Among these 9 proteins, S-nitrosylation of
      EMMPRIN and Golgi phosphoprotein 3 (GOLPH3) was verified in endothelial cells.
      Furthermore, S-nitrosylation of these proteins was found at the basal levels and
      increased in response to eNOS stimulation by the calcium ionophore A23187.
      Immunofluorescence microscopy and immunoprecipitation showed that EMMPRIN and
      GOLPH3 are co-localized with eNOS at the Golgi apparatus in endothelial cells. S
      nitrosylation of EMMPRIN was notably increased in the aorta of cirrhotic rats.
      CONCLUSION: Our data suggest that the selective S-nitrosylation of EMMPRIN and
      GOLPH3 at the Golgi apparatus in endothelial cells results from the physical
      proximity to eNOS-derived nitric oxide.

PMID- 22363675
TI  - Differential adhesive properties of sequestered asexual and sexual stages of
      Plasmodium falciparum on human endothelial cells are tissue independent.
AB  - The protozoan parasite Plasmodium falciparum, responsible for the most severe
      form of malaria, is able to sequester from peripheral circulation during
      infection. The asexual stage parasites sequester by binding to endothelial cell
      receptors in the microvasculature of various organs. P. falciparum gametocytes,
      the developmental stages responsible for parasite transmission from humans to
      Anopheles mosquitoes, also spend the almost ten days necessary for their
      maturation sequestered away from the peripheral circulation before they are
      released in blood mainstream. In contrast to those of asexual parasites, the
      mechanisms and cellular interactions responsible for immature gametocyte
      sequestration are largely unexplored, and controversial evidence has been
      produced so far on this matter. Here we present a systematic comparison of cell
      binding properties of asexual stages and immature and mature gametocytes from the
      reference P. falciparum clone 3D7 and from a patient parasite isolate on a panel
      of human endothelial cells from different tissues. This analysis includes assays
      on human bone marrow derived endothelial cell lines (HBMEC), as this tissue has
      been proposed as a major site of gametocyte maturation. Our results clearly
      demonstrate that cell adhesion of asexual stage parasites is consistently more
      efficient than that, virtually undetectable of immature gametocytes,
      irrespectively of the endothelial cell lines used and of parasite genotypes.
      Importantly, immature gametocytes of both lines tested here do not show a higher
      binding efficiency compared to asexual stages on bone marrow derived endothelial
      cells, unlike previously reported in the only study on this issue. This indicates
      that gametocyte-host interactions in this tissue are unlikely to be mediated by
      the same adhesion processes to specific endothelial receptors as seen with
      asexual forms.

PMID- 22363676
TI  - Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.
AB  - Naked mole-rats are highly social and strictly subterranean rodents that live in
      large communal colonies in sealed and chronically oxygen-depleted burrows. Brain
      slices from naked mole-rats show extreme tolerance to hypoxia compared to slices
      from other mammals, as indicated by maintenance of synaptic transmission under
      more hypoxic conditions and three fold longer latency to anoxic depolarization. A
      key factor in determining whether or not the cellular response to hypoxia is
      reversible or leads to cell death may be the elevation of intracellular calcium
      concentration. In the present study, we used fluorescent imaging techniques to
      measure relative intracellular calcium changes in CA1 pyramidal cells of
      hippocampal slices during hypoxia. We found that calcium accumulation during
      hypoxia was significantly and substantially attenuated in slices from naked mole
      rats compared to slices from laboratory mice. This was the case for both neonatal
      (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while
      both species demonstrated more calcium accumulation at older ages, the older
      naked mole-rats showed a smaller calcium accumulation response than even the
      younger mice. A blunted intracellular calcium response to hypoxia may contribute
      to the extreme hypoxia tolerance of naked mole-rat neurons. The results are
      discussed in terms of a general hypothesis that a very prolonged or arrested
      developmental process may allow adult naked mole-rat brain to retain the hypoxia
      tolerance normally only seen in neonatal mammals.

PMID- 22363673
TI  - Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection
      domain of HIV-1 reverse transcriptase.
AB  - BACKGROUND: We previously demonstrated in vitro that zidovudine (AZT) selects for
      A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of
      HIV-1 reverse transcriptase (RT) which, together with the thymidine analog
      mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The
      goal of the current study was to determine whether AZT monotherapy in HIV-1
      infected patients also selects the A371V, Q509L or other mutations in the C
      terminal domains of HIV-1 RT. METHODOLOGY/PRINCIPAL FINDINGS: Full-length RT
      sequences in plasma obtained pre- and post-therapy were compared in 23
      participants who received AZT monotherapy from the AIDS Clinical Trials Group
      study 175. Five of the 23 participants reached a primary study endpoint.
      Mutations significantly associated with AZT monotherapy included K70R (p = 0.003)
      and T215Y (p = 0.013) in the polymerase domain of HIV-1 RT, and A360V (p = 0.041)
      in the connection domain of HIV-1 RT. HIV-1 drug susceptibility assays
      demonstrated that A360V, either alone or in combination with thymidine analog
      mutations, decreased AZT susceptibility in recombinant viruses containing
      participant-derived full-length RT sequences or site-directed mutant RT.
      Biochemical studies revealed that A360V enhances the AZT-monophosphate excision
      activity of purified RT by significantly decreasing the frequency of secondary
      RNase H cleavage events that reduce the RNA/DNA duplex length and promote
      template/primer dissociation. CONCLUSIONS: The A360V mutation in the connection
      domain of RT was selected in HIV-infected individuals that received AZT
      monotherapy and contributed to AZT resistance.

PMID- 22363677
TI  - Role of histone acetylation in the stimulatory effect of valproic acid on
      vascular endothelial tissue-type plasminogen activator expression.
AB  - AIMS: Stimulated release of tissue-type plasminogen activator (t-PA) is pivotal
      for an intravascular fibrinolytic response and protects the circulation from
      occluding thrombosis. Hence, an impaired t-PA production is associated with
      increased risk for atherothrombotic events. A pharmacological means to stimulate
      the production of this enzyme may thus be desirable. We investigated if the anti
      epileptic drug valproic acid (VPA) is capable of enhancing t-PA expression in
      vitro in vascular endothelial cells, and further examined if its histone
      deacetylase (HDAC)-inhibitory activity is of importance for regulating t-PA
      expression. METHODS AND RESULTS: Human endothelial cells were exposed to valproic
      acid and t-PA mRNA and protein levels were quantified. Potential changes in
      histone acetylation status globally and at the t-PA promoter were examined by
      western blot and chromatin immunoprecipitation. Valproic acid dose-dependently
      stimulated t-PA mRNA and protein expression in endothelial cells reaching a 2-4
      fold increase at clinically relevant concentrations and 10-fold increase at
      maximal concentrations. Transcription profiling analysis revealed that t-PA is
      selectively targeted by this agent. Augmented histone acetylation was detected at
      the t-PA transcription start site, and an attenuated VPA-response was observed
      with siRNA knock of HDAC3, HDAC5 and HDAC7. CONCLUSIONS: Valproic acid induces t
      PA expression in cultured endothelial cells, and this is associated with
      increased histone acetylation at the t-PA promoter. Given the apparent potency of
      valproic acid in stimulating t-PA expression in vitro this substance may be a
      candidate for pharmacological modulation of endogenous fibrinolysis in man.

PMID- 22363678
TI  - Anti-inflammatory role of the cAMP effectors Epac and PKA: implications in
      chronic obstructive pulmonary disease.
AB  - Cigarette smoke-induced release of pro-inflammatory cytokines including
      interleukin-8 (IL-8) from inflammatory as well as structural cells in the
      airways, including airway smooth muscle (ASM) cells, may contribute to the
      development of chronic obstructive pulmonary disease (COPD). Despite the wide use
      of pharmacological treatment aimed at increasing intracellular levels of the
      endogenous suppressor cyclic AMP (cAMP), little is known about its exact
      mechanism of action. We report here that next to the beta(2)-agonist fenoterol,
      direct and specific activation of either exchange protein directly activated by
      cAMP (Epac) or protein kinase A (PKA) reduced cigarette smoke extract (CSE)
      induced IL-8 mRNA expression and protein release by human ASM cells. CSE-induced
      IkappaBalpha-degradation and p65 nuclear translocation, processes that were
      primarily reversed by Epac activation. Further, CSE increased extracellular
      signal-regulated kinase (ERK) phosphorylation, which was selectively reduced by
      PKA activation. CSE decreased Epac1 expression, but did not affect Epac2 and PKA
      expression. Importantly, Epac1 expression was also reduced in lung tissue from
      COPD patients. In conclusion, Epac and PKA decrease CSE-induced IL-8 release by
      human ASM cells via inhibition of NF-kappaB and ERK, respectively, pointing at
      these cAMP effectors as potential targets for anti-inflammatory therapy in COPD.
      However, cigarette smoke exposure may reduce anti-inflammatory effects of cAMP
      elevating agents via down-regulation of Epac1.

PMID- 22363680
TI  - Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and 
      independent human prostate cancer cells.
AB  - Prostate cancer is the most common malignancy in men. In the present study, LNCaP
      (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen
      independent human prostate cancer cells) were used to investigate the anti-cancer
      effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to
      determine the underlying mechanisms in vitro and in vivo. We found that IR
      combined with ATO increases the therapeutic efficacy compared to individual
      treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined
      treatment showed enhanced reactive oxygen species (ROS) generation compared to
      treatment with ATO or IR alone in PC-3 cells. Combined treatment induced
      autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3
      cells. The cell death that was induced by the combined treatment was primarily
      the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we
      found that the combined treatment of cells pre-treated with 3-MA resulted in a
      significant change in AO-positive cells and cytotoxicity. In an in vivo study,
      the combination treatment had anti-tumor growth effects. These novel findings
      suggest that combined treatment is a potential therapeutic strategy not only for
      androgen-dependent prostate cancer but also for androgen-independent prostate
      cancer.

PMID- 22363679
TI  - Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast
      cells.
AB  - Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by
      caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP,
      and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of
      these pathways in extending the lifespan of nutrient restricted yeast cells, but
      the mechanisms involved are still poorly understood. We have used gene expression
      microarrays to study the targets of Gis1 and the related protein Rph1 in
      different growth phases. Our results show that Gis1 and Rph1 act both as
      repressors and activators, on overlapping sets of genes as well as on distinct
      targets. Interestingly, both the activities and the target specificities of Gis1
      and Rph1 depend on the growth phase. Thus, both proteins are associated with
      repression during exponential growth, targeting genes with STRE or PDS motifs in
      their promoters. After the diauxic shift, both become involved in activation,
      with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE
      motifs. Significantly, Gis1 and Rph1 control a number of genes involved in
      acetate and glycerol formation, metabolites that have been implicated in aging.
      Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by
      Gis1.

PMID- 22363681
TI  - Phosphine resistance in the rust red flour beetle, Tribolium castaneum
      (Coleoptera: Tenebrionidae): inheritance, gene interactions and fitness costs.
AB  - The recent emergence of heritable high level resistance to phosphine in stored
      grain pests is a serious concern among major grain growing countries around the
      world. Here we describe the genetics of phosphine resistance in the rust red
      flour beetle Tribolium castaneum (Herbst), a pest of stored grain as well as a
      genetic model organism. We investigated three field collected strains of T.
      castaneum viz., susceptible (QTC4), weakly resistant (QTC1012) and strongly
      resistant (QTC931) to phosphine. The dose-mortality responses of their test- and
      inter-cross progeny revealed that most resistance was conferred by a single major
      resistance gene in the weakly (3.2*) resistant strain. This gene was also found
      in the strongly resistant (431*) strain, together with a second major resistance
      gene and additional minor factors. The second major gene by itself confers only
      12-20* resistance, suggesting that a strong synergistic epistatic interaction
      between the genes is responsible for the high level of resistance (431*) observed
      in the strongly resistant strain. Phosphine resistance is not sex linked and is
      inherited as an incompletely recessive, autosomal trait. The analysis of the
      phenotypic fitness response of a population derived from a single pair inter
      strain cross between the susceptible and strongly resistant strains indicated the
      changes in the level of response in the strong resistance phenotype; however this
      effect was not consistent and apparently masked by the genetic background of the
      weakly resistant strain. The results from this work will inform phosphine
      resistance management strategies and provide a basis for the identification of
      the resistance genes.

PMID- 22363682
TI  - The validity of d' measures.
AB  - Subliminal perception occurs when prime stimuli that participants claim not to be
      aware of nevertheless influence subsequent processing of a target. This claim,
      however, critically depends on correct methods to assess prime awareness.
      Typically, d' ("d prime") tasks administered after a priming task are used to
      establish that people are unable to discriminate between different primes. Here,
      we show that such d' tasks are influenced by the nature of the target, by
      attentional factors, and by the delay between stimulus presentation and response.
      Our results suggest that the standard d' task is not a straightforward measure of
      prime visibility. We discuss the implications of our findings for subliminal
      perception research.

PMID- 22363683
TI  - Translation initiation factor AteIF(iso)4E is involved in selective mRNA
      translation in Arabidopsis thaliana seedlings.
AB  - One of the most regulated steps of translation initiation is the recruitment of
      mRNA by the translation machinery. In eukaryotes, this step is mediated by the
      5'end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the
      eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the
      antigenically distinct eIF4F and eIF(iso)4F complexes proposed to mediate
      selective translation. Using a microarray analysis of polyribosome- and non
      polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT]
      and eIF(iso)4E knockout mutant [(iso)4E-1] seedlings we found 79 transcripts
      shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the
      opposite behavior in the knockout mutant. The translationally decreased mRNAs
      were overrepresented in root-preferentially expressed genes and proteins from the
      endomembrane system, including several transporters such as the phosphate
      transporter PHOSPHATE1 (PHO1), Sucrose transporter 3 (SUC3), ABC transporter-like
      with ATPase activity (MRP11) and five electron transporters, as well as signal
      transduction-, protein modification- and transcription-related proteins. Under
      normal growth conditions, eIF(iso)4E expression under the constitutive promoter
      35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational
      preference for eIF(iso)4E. Furthermore, under phosphate deficiency, the PHO1
      protein increased in the eIF(iso)4E overexpressing plants and decreased in the
      knockout mutant as compared to wild type. In addition, the knockout mutant had
      larger root, whereas the 35 S directed expression of eIF(iso)4E caused shorter
      root under normal growth conditions, but not under phosphate deficiency. These
      results indicate that selective translation mediated by eIF(iso)4E is relevant
      for Arabidopsis root development under normal growth conditions.

PMID- 22363684
TI  - Increased risk of breast cancer associated with CC genotype of Has-miR-146a
      Rs2910164 polymorphism in Europeans.
AB  - BACKGROUND: Emerging evidence suggests that microRNAs play a critical role in the
      pathogenesis of breast cancer. Several molecular epidemiological studies were
      conducted in recent years to evaluate the association between has-miR-146a
      rs2910164 polymorphism and breast cancer risk in diverse populations. However,
      the results remain conflicting rather than conclusive. METHODOLOGY/PRINCIPAL
      FINDINGS: We performed a meta-analysis of 6 case-control studies that included
      4238 breast-cancer cases and 4469 case-free controls. We assessed the strength of
      the association, using odds ratios (ORs) with 95% confidence intervals (CIs).
      Overall, this meta-analysis showed that the rs2910164 polymorphism was not
      associated with a significantly increased risk of breast cancer in all genetic
      models (for GC vs GG: OR = 1.00, 95% CI = 0.90-1.09, P(heterpgeneity) = 0.364;
      for CC vs GG: OR = 1.16, 95% CI = 0.98-1.36, P(heterpgeneity) = 0.757; for GC+CC
      vs GG: OR = 1.02, 95% CI = 0.93-1.12, P(heterpgeneity) = 0.562; for CC vs GC+GG:
      OR = 1.10, 95% CI = 0.96-1.26, P(heterpgeneity) = 0.441). However, in the
      stratified analysis by ethnicity, we found the rs2910164 polymorphism was
      associated with increased breast cancer risk among Europeans in homozygote
      comparison (CC vs. GG: OR = 1.29, 95%CI = 1.02-1.63, P(heterpgeneity) = 0.950, P
      = 0.032) and recessive model (CC vs. GC+GG: OR = 1.31, 95%CI = 1.05-1.65,
      P(heterpgeneity) = 0.839, P = 0.019). No publication bias was found in the
      present study. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests, for the
      first time, that the CC homozygote of rs2910164 may contribute to breast cancer
      susceptibility in Europeans.

PMID- 22363685
TI  - The effects of apolipoprotein F deficiency on high density lipoprotein
      cholesterol metabolism in mice.
AB  - Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides
      on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid
      Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl
      ester transfer protein (CETP)-mediated transfer events between lipoproteins. In
      contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic
      alpha helices and its true physiological function remains unknown. We previously
      showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol
      levels by 20-25% by accelerating clearance from the circulation. In order to
      investigate the effect of physiological levels of ApoF expression on HDL
      cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion
      of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid
      or protein composition. Sex-specific differences were observed in hepatic
      cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO
      mice had increased liver cholesteryl ester content relative to wild type controls
      on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05). No
      differences were observed in ABCG1-mediated cholesterol efflux capacity in either
      sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at
      promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT
      controls.

PMID- 22363686
TI  - Division of labor in the hyperdiverse ant genus Pheidole is associated with
      distinct subcaste- and age-related patterns of worker brain organization.
AB  - The evolutionary success of ants and other social insects is considered to be
      intrinsically linked to division of labor among workers. The role of the brains
      of individual ants in generating division of labor, however, is poorly
      understood, as is the degree to which interspecific variation in worker social
      phenotypes is underscored by functional neurobiological differentiation. Here we
      demonstrate that dimorphic minor and major workers of different ages from three
      ecotypical species of the hyperdiverse ant genus Pheidole have distinct patterns
      of neuropil size variation. Brain subregions involved in sensory input (optic and
      antennal lobes), sensory integration, learning and memory (mushroom bodies), and
      motor functions (central body and subesophageal ganglion) vary significantly in
      relative size, reflecting differential investment in neuropils that likely
      regulate subcaste- and age-correlated task performance. Worker groups differ in
      brain size and display patterns of altered isometric and allometric subregion
      scaling that affect brain architecture independently of brain size variation. In
      particular, mushroom body size was positively correlated with task plasticity in
      the context of both age- and subcaste-related polyethism, providing strong, novel
      support that greater investment in this neuropil increases behavioral
      flexibility. Our findings reveal striking levels of developmental plasticity and
      evolutionary flexibility in Pheidole worker neuroanatomy, supporting the
      hypothesis that mosaic alterations of brain composition contribute to adaptive
      colony structure and interspecific variation in social organization.

PMID- 22363687
TI  - Behavioural syndrome in a solitary predator is independent of body size and
      growth rate.
AB  - Models explaining behavioural syndromes often focus on state-dependency, linking
      behavioural variation to individual differences in other phenotypic features.
      Empirical studies are, however, rare. Here, we tested for a size and growth
      dependent stable behavioural syndrome in the juvenile-stages of a solitary apex
      predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk.
      Pike swimming activity, latency to prey attack, number of successful and
      unsuccessful prey attacks was measured during the presence/absence of visual
      contact with a competitor or predator. Foraging behaviour across risks was
      considered an appropriate indicator of boldness in this solitary predator where a
      trade-off between foraging behaviour and threat avoidance has been reported.
      Support was found for a behavioural syndrome, where the rank order differences in
      the foraging behaviour between individuals were maintained across time and risk
      situation. However, individual behaviour was independent of body size and growth
      in conditions of high food availability, showing no evidence to support the state
      dependent personality hypothesis. The importance of a combination of spatial and
      temporal environmental variation for generating growth differences is
      highlighted.

PMID- 22363688
TI  - Putative chemosensory receptors of the codling moth, Cydia pomonella, identified
      by antennal transcriptome analysis.
AB  - The codling moth, Cydia pomonella, is an important fruit pest worldwide. As
      nocturnal animals, adults depend to a large extent on olfactory cues for
      detection of food and mates, and, for females, oviposition sites. In insects,
      odor detection is mediated by odorant receptors (ORs) and ionotropic receptors
      (IRs), which ensure the specificity of the olfactory sensory neuron responses. In
      this study, our aim was to identify chemosensory receptors in the codling moth as
      a means to uncover new targets for behavioral interference. Using next-generation
      sequencing techniques, we identified a total of 43 candidate ORs, one gustatory
      receptor and 15 IRs in the antennal transcriptome. Through Blast and sequence
      similarity analyses we annotated the insect obligatory co-receptor ORco, five
      genes clustering in a conserved clade containing sex pheromone receptors, one
      homolog of the Bombyx mori female-enriched receptor BmorOR30 (but no homologs of
      the other B. mori female-enriched receptors) and one gene clustering in the sugar
      receptor family. Among the candidate IRs, we identified homologs of the two
      highly conserved co-receptors IR8a and IR25a, and one homolog of an IR involved
      in phenylethyl amine detection in Drosophila. Our results open for functional
      characterization of the chemosensory receptors of C. pomonella, with potential
      for new or refined applications of semiochemicals for control of this pest
      insect.

PMID- 22363689
TI  - Mechanisms underlying stage-1 TRPL channel translocation in Drosophila
      photoreceptors.
AB  - BACKGROUND: TRP channels function as key mediators of sensory transduction and
      other cellular signaling pathways. In Drosophila, TRP and TRPL are the light
      activated channels in photoreceptors. While TRP is statically localized in the
      signaling compartment of the cell (the rhabdomere), TRPL localization is
      regulated by light. TRPL channels translocate out of the rhabdomere in two
      distinct stages, returning to the rhabdomere with dark-incubation. Translocation
      of TRPL channels regulates their availability, and thereby the gain of the
      signal. Little, however, is known about the mechanisms underlying this
      trafficking of TRPL channels. METHODOLOGY/PRINCIPAL FINDINGS: We first examine
      the involvement of de novo protein synthesis in TRPL translocation. We feed flies
      cycloheximide, verify inhibition of protein synthesis, and test for TRPL
      translocation in photoreceptors. We find that protein synthesis is not involved
      in either stage of TRPL translocation out of the rhabdomere, but that re
      localization to the rhabdomere from stage-1, but not stage-2, depends on protein
      synthesis. We also characterize an ex vivo eye preparation that is amenable to
      biochemical and genetic manipulation. We use this preparation to examine
      mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is:
      induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton
      or inhibition of endocytosis, and slowed with increased membrane sterol content.
      CONCLUSIONS/SIGNIFICANCE: Our results indicate that translocation of TRPL out of
      the rhabdomere is likely due to protein transport, and not degradation/re
      synthesis. Re-localization from each stage to the rhabdomere likely involves
      different strategies. Since TRPL channels can translocate to stage-1 in the
      absence of ATP, with no major requirement of the cytoskeleton, we suggest that
      stage-1 translocation involves simple diffusion through the apical membrane,
      which may be regulated by release of a light-dependent anchor in the rhabdomere.

PMID- 22363691
TI  - Variation in protein intake induces variation in spider silk expression.
AB  - BACKGROUND: It is energetically expensive to synthesize certain amino acids. The
      proteins (spidroins) of spider major ampullate (MA) silk, MaSp1 and MaSp2, differ
      in amino acid composition. Glutamine and proline are prevalent in MaSp2 and are
      expensive to synthesize. Since most orb web spiders express high proline silk
      they might preferentially attain the amino acids needed for silk from food and
      shift toward expressing more MaSp1 in their MA silk when starved.
      METHODOLOGY/PRINCIPAL FINDINGS: We fed three spiders; Argiope aetherea,
      Cyrtophora moluccensis and Leucauge blanda, high protein, low protein or no
      protein solutions. A. aetherea and L. blanda MA silks are high in proline, while
      C. moluccesnsis MA silks are low in proline. After 10 days of feeding we
      determined the amino acid compositions and mechanical properties of each species'
      MA silk and compared them between species and treatments with pre-treatment
      samples, accounting for ancestry. We found that the proline and glutamine of A.
      aetherea and L. blanda silks were affected by protein intake; significantly
      decreasing under the low and no protein intake treatments. Glutmaine composition
      in C. moluccensis silk was likewise affected by protein intake. However, the
      composition of proline in their MA silk was not significantly affected by protein
      intake. CONCLUSIONS: Our results suggest that protein limitation induces a shift
      toward different silk proteins with lower glutamine and/or proline content.
      Contradictions to the MaSp model lie in the findings that C. moluccensis MA silks
      did not experience a significant reduction in proline and A. aetherea did not
      experience a significant reduction in serine on low/no protein. The mechanical
      properties of the silks could not be explained by a MaSp1 expressional shift.
      Factors other than MaSp expression, such as the expression of spidroin-like
      orthologues, may impact on silk amino acid composition and spinning and glandular
      processes may impact mechanics.

PMID- 22363690
TI  - Interleukin-15 plays a central role in human kidney physiology and cancer through
      the gammac signaling pathway.
AB  - The ability of Interleukin-15 (IL-15) to activate many immune antitumor
      mechanisms renders the cytokine a good candidate for the therapy of solid tumors,
      particularly renal cell carcinoma. Although IL-15 is being currently used in
      clinical trials, the function of the cytokine on kidney's components has not been
      extensively studied; we thus investigated the role of IL-15 on normal and tumor
      renal epithelial cells. Herein, we analyzed the expression and the biological
      functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their
      neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows
      that RPTEC express a functional heterotrimeric IL-15Ralphabetagammac complex
      whose stimulation with physiologic concentrations of rhIL-15 is sufficient to
      inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin
      expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but
      it can also preserve the renal epithelial phenotype through the gammac-signaling
      pathway, demonstrating that the cytokine possess a wide range of action in
      epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a
      defect in the expression of gammac-receptor and JAK3 associated kinase, which
      strongly impacts IL-15 signaling. Indeed, in the absence of the gammac/JAK3
      couple we demonstrate the assembly of an unprecedented functional high affinity
      IL-15Ralphabeta heterodimer, that in response to physiologic concentrations of IL
      15, triggers an unbalanced signal causing the down-regulation of the tumor
      suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of
      IL-15/gammac-dependent signaling (STAT5), by co-transfecting gammac and JAK3 in
      RCC, inhibits EMT reversion. In conclusion, these data highlight the central role
      of IL-15 and gammac-receptor signaling in renal homeostasis through the control
      of E-cadherin expression and preservation of epithelial phenotype both in RPTEC
      (up-regulation) and RCC (down-regulation).

PMID- 22363692
TI  - Dispersal of adult black marlin (Istiompax indica) from a Great Barrier Reef
      spawning aggregation.
AB  - The black marlin (Istiompax indica) is one of the largest bony fishes in the
      world with females capable of reaching a mass of over 700 kg. This highly
      migratory predator occurs in the tropical regions of the Pacific and Indian
      Oceans, and is the target of regional recreational and commercial fisheries.
      Through the sampling of ichthyoplankton and ovaries we provide evidence that the
      relatively high seasonal abundance of black marlin off the Great Barrier Reef is,
      in fact, a spawning aggregation. Furthermore, through the tracking of individual
      black marlin via satellite popup tags, we document the dispersal of adult black
      marlin away from the spawning aggregation, thereby identifying the catchment area
      for this spawning stock. Although tag shedding is an issue when studying
      billfish, we tentatively identify the catchment area for this stock of black
      marlin to extend throughout the Coral Sea, including the waters of Papua New
      Guinea, the Solomon Islands, Micronesia, New Caledonia, Kiribati, Vanuatu, Fiji,
      Tuvalu and Nauru.

PMID- 22363693
TI  - Optimizing a massive parallel sequencing workflow for quantitative miRNA
      expression analysis.
AB  - BACKGROUND: Massive Parallel Sequencing methods (MPS) can extend and improve the
      knowledge obtained by conventional microarray technology, both for mRNAs and
      short non-coding RNAs, e.g. miRNAs. The processing methods used to extract and
      interpret the information are an important aspect of dealing with the vast
      amounts of data generated from short read sequencing. Although the number of
      computational tools for MPS data analysis is constantly growing, their strengths
      and weaknesses as part of a complex analytical pipe-line have not yet been well
      investigated. PRIMARY FINDINGS: A benchmark MPS miRNA dataset, resembling a
      situation in which miRNAs are spiked in biological replication experiments was
      assembled by merging a publicly available MPS spike-in miRNAs data set with MPS
      data derived from healthy donor peripheral blood mononuclear cells. Using this
      data set we observed that short reads counts estimation is strongly under
      estimated in case of duplicates miRNAs, if whole genome is used as reference.
      Furthermore, the sensitivity of miRNAs detection is strongly dependent by the
      primary tool used in the analysis. Within the six aligners tested, specifically
      devoted to miRNA detection, SHRiMP and MicroRazerS show the highest sensitivity.
      Differential expression estimation is quite efficient. Within the five tools
      investigated, two of them (DESseq, baySeq) show a very good specificity and
      sensitivity in the detection of differential expression. CONCLUSIONS: The results
      provided by our analysis allow the definition of a clear and simple analytical
      optimized workflow for miRNAs digital quantitative analysis.

PMID- 22363694
TI  - High glucose decreases expression and activity of p-glycoprotein in cultured
      human retinal pigment epithelium possibly through iNOS induction.
AB  - Inhibition of p-glycoprotein under hyperglycemic conditions has been reported in
      various barrier tissues including blood-brain barrier, intestine, and kidney, and
      has been linked to significant clinical complications. However, whether this is
      also true for the outer blood-retinal barrier constituted by retinal pigment
      epithelium, or has a role in pathogenesis of diabetic retinopathy is not yet
      clear. In this study, using cultured human retinal pigment epithelium cell line
      D407, we found that high glucose exposure induced a significant decrease in p
      glycoprotein expression both at mRNA and at protein levels, accompanied by an
      attenuated p-glycoprotein activity determined by intracellular rhodamine 123
      retention. In marked contrast, the expressions of both mRNA and protein levels of
      inducible nitrate oxide synthase (iNOS) increased, and were accompanied by
      increased extracellular nitrate/nitrite production by Griess reaction. In
      addition, mRNA levels of nuclear receptors revealed a decreased expression of
      pregnane X receptor after the exposure of high glucose. However, the subsequent
      alterations in production of nitrate/nitrite, functional expression of p
      glycoprotein, and mRNA levels of pregnane X receptor were partially blocked when
      pretreated with S,S'-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea*2HBr
      (PBITU), a selective iNOS inhibitor. Moreover, the effects of PBITU were
      antagonized with the addition of L-arginine, a substrate for NO synthesis. Our in
      vitro results suggest for the first time that iNOS induction plays a novel role
      in decreased p-glycoprotein expression and transport function at the human outer
      blood-retinal barrier under hyperglycemic conditions and further support the
      concept of inhibiting iNOS pathway as a therapeutic strategy for diabetic
      retinopathy.

PMID- 22363695
TI  - Prolonged exposure to a Mer ligand in leukemia: Gas6 favors expression of a
      partial Mer glycoform and reveals a novel role for Mer in the nucleus.
AB  - Mer tyrosine kinase is ectopically expressed in acute lymphoblastic leukemia and
      associated with enhanced chemoresistance and disease progression. While such
      effects are generally ascribed to increased engagement of oncogenic pathways
      downstream of Mer stimulation by its ligand, Gas6, Mer has not been characterized
      beyond the scope of its signaling activity. The present study explores Mer
      behavior following prolonged exposure to Gas6, a context similar to the Gas6
      enriched microenvironment of the bone marrow, where a steady supply of ligand
      facilitates continuous engagement of Mer and likely sustains the presence of
      leukemic cells. Long-term Gas6 exposure induced production of a partially N
      glycosylated form of Mer from newly synthesized stores of protein. Preferential
      expression of the partial Mer glycoform was associated with diminished levels of
      Mer on the cell surface and altered Mer localization within the nuclear-soluble
      and chromatin-bound fractions. The presence of Mer in the nucleus is a novel
      finding for this receptor, and the glycoform-specific preferences observed in
      each nuclear compartment suggest that glycosylation may influence Mer function
      within particular subcellular locales. Previous studies have established Mer as
      an attractive cancer biologic target, and understanding the complexity of its
      activity has important implications for potential strategies of Mer inhibition in
      leukemia therapy. Our results identify several novel features of Mer that expand
      the breadth of its functions and impact the development of therapeutic modalities
      designed to target Mer.

PMID- 22363696
TI  - alpha-Calcium calmodulin kinase II modulates the temporal structure of
      hippocampal bursting patterns.
AB  - The alpha calcium calmodulin kinase II (alpha-CaMKII) is known to play a key role
      in CA1/CA3 synaptic plasticity, hippocampal place cell stability and spatial
      learning. Additionally, there is evidence from hippocampal electrophysiological
      slice studies that this kinase has a role in regulating ion channels that control
      neuronal excitability. Here, we report in vivo single unit studies, with alpha
      CaMKII mutant mice, in which threonine 305 was replaced with an aspartate (alpha
      CaMKII(T305D) mutants), that indicate that this kinase modulates spike patterns
      in hippocampal pyramidal neurons. Previous studies showed that alpha
      CaMKII(T305D) mutants have abnormalities in both hippocampal LTP and hippocampal
      dependent learning. We found that besides decreased place cell stability, which
      could be caused by their LTP impairments, the hippocampal CA1 spike patterns of
      alpha-CaMKII(T305D) mutants were profoundly abnormal. Although overall firing
      rate, and overall burst frequency were not significantly altered in these
      mutants, inter-burst intervals, mean number of intra-burst spikes, ratio of intra
      burst spikes to total spikes, and mean intra-burst intervals were significantly
      altered. In particular, the intra burst intervals of place cells in alpha
      CaMKII(T305D) mutants showed higher variability than controls. These results
      provide in vivo evidence that besides its well-known function in synaptic
      plasticity, alpha-CaMKII, and in particular its inhibitory phosphorylation at
      threonine 305, also have a role in shaping the temporal structure of hippocampal
      burst patterns. These results suggest that some of the molecular processes
      involved in acquiring information may also shape the patterns used to encode this
      information.

PMID- 22363697
TI  - Role of Chd7 in zebrafish: a model for CHARGE syndrome.
AB  - CHARGE syndrome is caused by mutations in the CHD7 gene. Several organ systems
      including the retina, cranial nerves, inner ear and heart are affected in CHARGE
      syndrome. However, the mechanistic link between mutations in CHD7 and many of the
      organ systems dysfunction remains elusive. Here, we show that Chd7 is required
      for the organization of the neural retina in zebrafish. We observe an abnormal
      expression or a complete absence of molecular markers for the retinal ganglion
      cells and photoreceptors, indicating that Chd7 regulates the differentiation of
      retinal cells and plays an essential role in retinal cell development. In
      addition, zebrafish with reduced Chd7 display an abnormal organization and
      clustering of cranial motor neurons. We also note a pronounced reduction in the
      facial branchiomotor neurons and the vagal motor neurons display aberrant
      positioning. Further, these fish exhibit a severe loss of the facial nerves.
      Knock-down of Chd7 results in a curvature of the long body axis and these fish
      develop irregular shaped vertebrae and have a reduction in bone mineralization.
      Chd7 knockdown also results in a loss of proper segment polarity illustrated by
      flawed efnb2a and ttna expression, which is associated with later vascular
      segmentation defects. These critical roles for Chd7 in retinal and vertebral
      development were previously unrecognized and our results provide new insights
      into the role of Chd7 during development and in CHARGE syndrome pathogenesis.

PMID- 22363698
TI  - Epstein-Barr virus infection and sporadic breast cancer risk: a meta-analysis.
AB  - BACKGROUND: A large number of epidemiological studies have evaluated the
      association between Epstein-Barr virus infection and breast carcinoma risk but
      results have been inconsistent. METHODOLOGY: Research using the polymerase chain
      reaction technique for detecting the Epstein-Barr virus was selected; 24 studies
      and 1535 cases were reviewed. Information on the study populations, sample types,
      publication calendar period and histological types of breast carcinoma were
      collected. An unconditional logistic regression model was used to analyze
      potential parameters related to the Epstein-Barr virus prevalence. A Kappa test
      was used to evaluate the consistency in detecting different Epstein-Barr virus
      DNA regions. Nine studies that included control groups and 1045 breast cancer
      cases were adopted in this meta-analysis. CONCLUSIONS: We found that 29.32% of
      the patients with breast carcinoma were infected with the Epstein-Barr virus. The
      prevalence of Epstein-Barr was highest in Asia (35.25%) and lowest in the USA
      (18.27%). Statistical analysis revealed a trend that showed lobular breast
      carcinoma might have the strongest association with Epstein-Barr virus infection.
      This meta-analysis showed a significant increase in breast malignancy risk in
      patients testing positive for the Epstein-Barr virus (OR = 6.29, 95% CI = 2.13
      18.59). This result suggests that an Epstein-Barr virus infection is
      statistically associated with increased breast carcinoma risk.

PMID- 22363699
TI  - Electrophysiological correlates of strategic monitoring in event-based and time
      based prospective memory.
AB  - Prospective memory (PM) is the ability to remember to accomplish an action when a
      particular event occurs (i.e., event-based PM), or at a specific time (i.e., time
      based PM) while performing an ongoing activity. Strategic Monitoring is one of
      the basic cognitive functions supporting PM tasks, and involves two mechanisms: a
      retrieval mode, which consists of maintaining active the intention in memory; and
      target checking, engaged for verifying the presence of the PM cue in the
      environment. The present study is aimed at providing the first evidence of event
      related potentials (ERPs) associated with time-based PM, and at examining
      differences and commonalities in the ERPs related to Strategic Monitoring
      mechanisms between event- and time-based PM tasks.The addition of an event-based
      or a time-based PM task to an ongoing activity led to a similar sustained
      positive modulation of the ERPs in the ongoing trials, mainly expressed over
      prefrontal and frontal regions. This modulation might index the retrieval mode
      mechanism, similarly engaged in the two PM tasks. On the other hand, two further
      ERP modulations were shown specifically in an event-based PM task. An increased
      positivity was shown at 400-600 ms post-stimulus over occipital and parietal
      regions, and might be related to target checking. Moreover, an early modulation
      at 130-180 ms post-stimulus seems to reflect the recruitment of attentional
      resources for being ready to respond to the event-based PM cue. This latter
      modulation suggests the existence of a third mechanism specific for the event
      based PM; that is, the "readiness mode".

PMID- 22363700
TI  - The incidence and repetition of hospital-treated deliberate self harm: findings
      from the world's first national registry.
AB  - BACKGROUND: Suicide is a significant public health issue with almost one million
      people dying by suicide each year worldwide. Deliberate self harm (DSH) is the
      single most important risk factor for suicide yet few countries have reliable
      data on DSH. We developed a national DSH registry in the Republic of Ireland to
      establish the incidence of hospital-treated DSH at national level and the
      spectrum and pattern of presentations with DSH and repetition. METHODS AND
      FINDINGS: Between 2003 and 2009, the Irish National Registry of Deliberate Self
      Harm collected data on DSH presentations to all 40 hospital emergency departments
      in the country. Data were collected by trained data registration officers using
      standard methods of case ascertainment and definition. The Registry recorded
      75,119 DSH presentations involving 48,206 individuals. The total incidence rate
      fell from 209 (95% CI: 205-213) per 100,000 in 2003 to 184 (95% CI: 180-189) per
      100,000 in 2006 and increased again to 209 (95% CI: 204-213) per 100,000 in 2009.
      The most notable annual changes were successive 10% increases in the male rate in
      2008 and 2009. There was significant variation by age with peak rates in women in
      the 15-19 year age group (620 (95% CI: 605-636) per 100,000), and in men in the
      20-24 age group (427 (95% CI: 416-439) per 100,000). Repetition rates varied
      significantly by age, method of self harm and number of previous episodes.
      CONCLUSIONS: Population-based data on hospital-treated DSH represent an important
      index of the burden of mental illness and suicide risk in the community. The
      increased DSH rate in Irish men in 2008 and 2009 coincided with the advent of the
      economic recession in Ireland. The findings underline the need for developing
      effective interventions to reduce DSH repetition rates as a key priority for
      health systems.

PMID- 22363702
TI  - Selection of reserves for woodland caribou using an optimization approach.
AB  - Habitat protection has been identified as an important strategy for the
      conservation of woodland caribou (Rangifer tarandus). However, because of the
      economic opportunity costs associated with protection it is unlikely that all
      caribou ranges can be protected in their entirety. We used an optimization
      approach to identify reserve designs for caribou in Alberta, Canada, across a
      range of potential protection targets. Our designs minimized costs as well as
      three demographic risk factors: current industrial footprint, presence of white
      tailed deer (Odocoileus virginianus), and climate change. We found that, using
      optimization, 60% of current caribou range can be protected (including 17% in
      existing parks) while maintaining access to over 98% of the value of resources on
      public lands. The trade-off between minimizing cost and minimizing demographic
      risk factors was minimal because the spatial distributions of cost and risk were
      similar. The prospects for protection are much reduced if protection is directed
      towards the herds that are most at risk of near-term extirpation.

PMID- 22363701
TI  - CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from
      CD200 receptor positive macrophage-like cells.
AB  - Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in
      vitro and the potential has also been transferred successfully to clinical trials
      for treatment of autoimmune diseases. OX-2 (CD200), a member of the
      immunoglobulin superfamily, is widely expressed in several tissues and has
      recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in
      myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several
      immune cells, especially macrophages. The present study on 20 hMSC lines shows
      that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me)
      and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines,
      whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were
      constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs
      mediated immunosuppression was studied using THP-1 human macrophages.
      Interestingly, hMSCs showed greater inhibition of TNF-alpha secretion in co
      cultures with IFN-gamma primed THP-1 macrophages when compared to LPS activated
      cells. The ability of CD200Hi BMMSCs to suppress TNF-alpha secretion from IFN
      gamma stimulated THP-1 macrophages was significantly greater when compared to
      CD200Lo whereas UCBMSCs did not significantly reduce TNF-alpha secretion. The
      interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the
      capability of BMMSCs to inhibit TNF-alpha secretion from IFN-gamma activated THP
      1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to
      suppress TNF-alpha secretion of THP-1 macrophages was dependent on the type of
      stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified
      role in the BMMSC mediated immunosuppression.

PMID- 22363703
TI  - Structural view of a non Pfam singleton and crystal packing analysis.
AB  - BACKGROUND: Comparative genomic analysis has revealed that in each genome a large
      number of open reading frames have no homologues in other species. Such singleton
      genes have attracted the attention of biochemists and structural biologists as a
      potential untapped source of new folds. Cthe_2751 is a 15.8 kDa singleton from an
      anaerobic, hyperthermophile Clostridium thermocellum. To gain insights into the
      architecture of the protein and obtain clues about its function, we decided to
      solve the structure of Cthe_2751. RESULTS: The protein crystallized in 4
      different space groups that diffracted X-rays to 2.37 A (P3(1)21), 2.17 A
      (P2(1)2(1)2(1)), 3.01 A (P4(1)22), and 2.03 A (C222(1)) resolution, respectively.
      Crystal packing analysis revealed that the 3-D packing of Cthe_2751 dimers in
      P4(1)22 and C222(1) is similar with only a rotational difference of 2.69 degrees 
      around the C axes. A new method developed to quantify the differences in packing
      of dimers in crystals from different space groups corroborated the findings of
      crystal packing analysis. Cthe_2751 is an all alpha-helical protein with a
      central hydrophobic core providing thermal stability via pi:cation and pi: pi
      interactions. A ProFunc analysis retrieved a very low match with a splicing
      endonuclease, suggesting a role for the protein in the processing of nucleic
      acids. CONCLUSIONS: Non-Pfam singleton Cthe_2751 folds into a known all alpha
      helical fold. The structure has increased sequence coverage of non-Pfam proteins
      such that more protein sequences can be amenable to modelling. Our work on
      crystal packing analysis provides a new method to analyze dimers of the protein
      crystallized in different space groups. The utility of such an analysis can be
      expanded to oligomeric structures of other proteins, especially receptors and
      signaling molecules, many of which are known to function as oligomers.

PMID- 22363704
TI  - Effectiveness of terbutaline pump for the prevention of preterm birth. A
      systematic review and meta-analysis.
AB  - BACKGROUND: Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in
      pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following
      acute treatment of preterm contractions. The effectiveness and safety of this
      maintenance tocolysis have not been clearly established. We aimed to
      systematically evaluate the effectiveness and safety of subcutaneous (SQ)
      terbutaline infusion by pump for maintenance tocolysis. METHODOLOGY/PRINCIPAL
      FINDINGS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews
      and Dissemination databases, post-marketing surveillance data and grey literature
      were searched up to April 2011 for relevant experimental and observational
      studies. Two randomized trials, one nonrandomized trial, and 11 observational
      studies met inclusion criteria. Non-comparative studies were considered only for
      pump-related harms. We excluded case-reports but sought FDA summaries of post
      marketing surveillance data. Non-English records without an English abstract were
      excluded. Evidence of low strength from observational studies with risk of bias
      favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks,
      mean days of pregnancy prolongation, and neonatal death. Observational studies of
      medium to high risk of bias also demonstrated benefit for other surrogate
      outcomes, such as birthweight and neonatal intensive care unit (NICU) admission.
      Several cases of maternal deaths and maternal cardiovascular events have been
      reported in patients receiving terbutaline tocolysis. CONCLUSIONS/SIGNIFICANCE:
      Although evidence suggests that pump therapy may be beneficial as maintenance
      tocolysis, our confidence in its validity and reproducibility is low, suggesting
      that its use should be limited to the research setting. Concerns regarding safety
      of therapy persist.

PMID- 22363705
TI  - Identification of mammalian protein quality control factors by high-throughput
      cellular imaging.
AB  - Protein Quality Control (PQC) pathways are essential to maintain the equilibrium
      between protein folding and the clearance of misfolded proteins. In order to
      discover novel human PQC factors, we developed a high-content, high-throughput
      cell-based assay to assess PQC activity. The assay is based on a fluorescently
      tagged, temperature sensitive PQC substrate and measures its degradation relative
      to a temperature insensitive internal control. In a targeted screen of 1591 siRNA
      genes involved in the Ubiquitin-Proteasome System (UPS) we identified 25 of the
      33 genes encoding for 26S proteasome subunits and discovered several novel PQC
      factors. An unbiased genome-wide siRNA screen revealed the protein translation
      machinery, and in particular the EIF3 translation initiation complex, as a novel
      key modulator of misfolded protein stability. These results represent a
      comprehensive unbiased survey of human PQC components and establish an
      experimental tool for the discovery of genes that are required for the
      degradation of misfolded proteins under conditions of proteotoxic stress.

PMID- 22363707
TI  - Phosphorylation of LCRMP-1 by GSK3beta promotes filopoda formation, migration and
      invasion abilities in lung cancer cells.
AB  - LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion
      and associate with poor clinical outcome in patients with non-small-cell lung
      cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in
      cancer cell invasiveness still remain obscure. Here, we report that GSK3beta can
      phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation
      is crucial for function of LCRMP-1 to promote filopodia formation, migration and
      invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the
      stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion
      abilities in cancer cells; simultaneously, kinase-dead GSK3beta diminishes
      regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that
      patients with low-level Ser-9-phosphorylated GSK3beta expression and high-level
      LCRMP-1 expression have worse overall survival than those with high-level
      inactive GSK3beta expressions and low-level LCRMP-1 expressions (P<0.0001).
      Collectively, these results demonstrate that GSK3beta-dependent phosphorylation
      of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer
      cell invasiveness and clinical outcome.

PMID- 22363706
TI  - The nitric oxide pathway provides innate antiviral protection in conjunction with
      the type I interferon pathway in fibroblasts.
AB  - The innate host response to virus infection is largely dominated by the
      production of type I interferon and interferon stimulated genes. In particular,
      fibroblasts respond robustly to viral infection and to recognition of viral
      signatures such as dsRNA with the rapid production of type I interferon;
      subsequently, fibroblasts are a key cell type in antiviral protection. We
      recently found, however, that primary fibroblasts deficient for the production of
      interferon, interferon stimulated genes, and other cytokines and chemokines mount
      a robust antiviral response against both DNA and RNA viruses following
      stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic
      functions; its production by phagocytes in response to interferon-gamma is
      associated with antimicrobial activity. Here we show that in response to dsRNA,
      nitric oxide is rapidly produced in primary fibroblasts. In the presence of an
      intact interferon system, nitric oxide plays a minor but significant role in
      antiviral protection. However, in the absence of an interferon system, nitric
      oxide is critical for the protection against DNA viruses. In primary fibroblasts,
      NF-kappaB and interferon regulatory factor 1 participate in the induction of
      inducible nitric oxide synthase expression, which subsequently produces nitric
      oxide. As large DNA viruses encode multiple and diverse immune modulators to
      disable the interferon system, it appears that the nitric oxide pathway serves as
      a secondary strategy to protect the host against viral infection in key cell
      types, such as fibroblasts, that largely rely on the type I interferon system for
      antiviral protection.

PMID- 22363708
TI  - Transcriptional repressor NIR functions in the ribosome RNA processing of both
      40S and 60S subunits.
AB  - BACKGROUND: NIR was identified as an inhibitor of histone acetyltransferase and
      it represses transcriptional activation of p53. NIR is predominantly localized in
      the nucleolus and known as Noc2p, which is involved in the maturation of the 60S
      ribosomal subunit. However, how NIR functions in the nucleolus remains
      undetermined. In the nucleolus, a 47S ribosomal RNA precursor (pre-rRNA) is
      transcribed and processed to produce 18S, 5.8S and 28S rRNAs. The 18S rRNA is
      incorporated into the 40S ribosomal subunit, whereas the 28S and 5.8S rRNAs are
      incorporated into the 60S subunit. U3 small nucleolar RNA (snoRNA) directs 18S
      rRNA processing and U8 snoRNA mediates processing of 28S and 5.8 S rRNAs.
      Functional disruption of nucleolus often causes p53 activation to inhibit cell
      proliferation. METHODOLOGY/PRINCIPAL FINDINGS: Western blotting showed that NIR
      is ubiquitously expressed in different human cell lines. Knock-down of NIR by
      siRNA led to inhibition of the 18S, 28S and 5.8S rRNAs evaluated by pulse-chase
      experiment. Pre-rRNA particles (pre-rRNPs) were fractionated from the nucleus by
      sucrose gradient centrifugation and analysis of the pre-RNPs components showed
      that NIR existed in the pre-RNPs of both the 60S and 40S subunits and co
      fractionated with 32S and 12S pre-rRNAs in the 60S pre-rRNP. Protein-RNA binding
      experiments demonstrated that NIR is associated with the 32S pre-rRNA and U8
      snoRNA. In addition, NIR bound U3 snoRNA. It is a novel finding that depletion of
      NIR did not affect p53 protein level but de-repressed acetylation of p53 and
      activated p21. CONCLUSIONS: We provide the first evidence for a transcriptional
      repressor to function in the rRNA biogenesis of both the 40S and 60S subunits.
      Our findings also suggested that a nucleolar protein may alternatively signal to
      p53 by affecting the p53 modification rather than affecting p53 protein level.

PMID- 22363710
TI  - Behaviour of solitary adult Scandinavian brown bears (Ursus arctos) when
      approached by humans on foot.
AB  - Successful management has brought the Scandinavian brown bear (Ursus arctos L.)
      back from the brink of extinction, but as the population grows and expands the
      probability of bear-human encounters increases. More people express concerns
      about spending time in the forest, because of the possibility of encountering
      bears, and acceptance for the bear is decreasing. In this context, reliable
      information about the bear's normal behaviour during bear-human encounters is
      important. Here we describe the behaviour of brown bears when encountering humans
      on foot. During 2006-2009, we approached 30 adult (21 females, 9 males) GPS
      collared bears 169 times during midday, using 1-minute positioning before, during
      and after the approach. Observer movements were registered with a handheld GPS.
      The approaches started 869+/-348 m from the bears, with the wind towards the bear
      when passing it at approximately 50 m. The bears were detected in 15% of the
      approaches, and none of the bears displayed any aggressive behaviour. Most bears
      (80%) left the initial site during the approach, going away from the observers,
      whereas some remained at the initial site after being approached (20%). Young
      bears left more often than older bears, possibly due to differences in
      experience, but the difference between ages decreased during the berry season
      compared to the pre-berry season. The flight initiation distance was longer for
      active bears (115+/-94 m) than passive bears (69+/-47 m), and was further
      affected by horizontal vegetation cover and the bear's age. Our findings show
      that bears try to avoid confrontations with humans on foot, and support the
      conclusions of earlier studies that the Scandinavian brown bear is normally not
      aggressive during encounters with humans.

PMID- 22363711
TI  - Testing strength of biotic resistance against an introduced fish: inter-specific
      competition or predation through facultative piscivory?
AB  - Biotic resistance is the process where aspects of the receiving environment
      inhibit the establishment and invasion of an introduced species. Resistance
      against an introduced fish can be through strong competition and/or predation
      from resident fishes. Here, the biotic resistance against introduced topmouth
      gudgeon Pseudorasbora parva (a highly invasive fish in Europe) by resident carp
      Cyprinus carpio was tested in experimental mesocosms. The introduction scenario
      was six adult P. parva (three male, three female) on a single occasion.
      Resistance to their establishment was provided by three and six resident C.
      carpio whose effects on P. parva growth and reproduction were compared to a
      Control (no resident fish at the time of introduction) and treatments containing
      three and six P. parva. After 120 days, the growth rates of the introduced P.
      parva were significantly depressed in C. carpio presence and in mesocosms with
      three C. carpio present, significantly decreased numbers of 0+P. parva were
      recorded. Where six C. carpio were present, no 0+P. parva were recorded,
      indicating resistance strength increased with carp abundance. In contrast, there
      were no differences in P. parva reproduction and growth rates between the Control
      and treatments containing conspecifics. Stable isotope analysis (delta(15)N,
      delta(13)C) revealed C. carpio were feeding at one trophic level above 0+P.
      parva, suggesting the process of resistance was predation (facultative piscivory)
      rather than competition. Thus, if P. parva are to establish and invade following
      an introduction, they must overcome this biotic resistance from cyprinid fishes
      such as C. carpio.

PMID- 22363709
TI  - Tachykinins stimulate a subset of mouse taste cells.
AB  - The tachykinins substance P (SP) and neurokinin A (NKA) are present in
      nociceptive sensory fibers expressing transient receptor potential cation
      channel, subfamily V, member 1 (TRPV1). These fibers are found extensively in and
      around the taste buds of several species. Tachykinins are released from
      nociceptive fibers by irritants such as capsaicin, the active compound found in
      chili peppers commonly associated with the sensation of spiciness. Using real
      time Ca(2+)-imaging on isolated taste cells, it was observed that SP induces
      Ca(2+) -responses in a subset of taste cells at concentrations in the low
      nanomolar range. These responses were reversibly inhibited by blocking the SP
      receptor NK-1R. NKA also induced Ca(2+)-responses in a subset of taste cells, but
      only at concentrations in the high nanomolar range. These responses were only
      partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited
      by blocking NK-1R indicating that NKA is only active in taste cells at
      concentrations that activate both receptors. In addition, it was determined that
      tachykinin signaling in taste cells requires Ca(2+)-release from endoplasmic
      reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express
      NK-1R and NK-2R. Using Ca(2+)-imaging and single cell RT-PCR, it was determined
      that the majority of tachykinin-responsive taste cells were Type I (Glial-like)
      and umami-responsive Type II (Receptor) cells. Importantly, stimulating NK-1R had
      an additive effect on Ca(2+) responses evoked by umami stimuli in Type II
      (Receptor) cells. This data indicates that tachykinin release from nociceptive
      sensory fibers in and around taste buds may enhance umami and other taste
      modalities, providing a possible mechanism for the increased palatability of
      spicy foods.

PMID- 22363712
TI  - Differentiation and recruitment of Th9 cells stimulated by pleural mesothelial
      cells in human Mycobacterium tuberculosis infection.
AB  - Newly discovered IL-9-producing CD4(+) helper T cells (Th9 cells) have been
      reported to contribute to tissue inflammation and immune responses, however,
      differentiation and immune regulation of Th9 cells in tuberculosis remain
      unknown. In the present study, our data showed that increased Th9 cells with the
      phenotype of effector memory cells were found to be in tuberculous pleural
      effusion as compared with blood. TGF-beta was essential for Th9 cell
      differentiation from naive CD4(+) T cells stimulated with PMA and ionomycin in
      vitro for 5 h, and addition of IL-1beta, IL-4 or IL-6 further augmented Th9 cell
      differentiation. Tuberculous pleural effusion and supernatants of cultured
      pleural mesothelial cells were chemotactic for Th9 cells, and this activity was
      partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell
      repairing and inhibited IFN-gamma-induced pleural mesothelial cell apoptosis.
      Moreover, pleural mesothelial cells promoted Th9 cell differentiation by
      presenting antigen. Collectively, these data provide new information concerning
      Th9 cells, in particular the collaborative immune regulation between Th9 cells
      and pleural mesothelial cells in human M. tuberculosis infection. In particular,
      pleural mesothelial cells were able to function as antigen-presenting cells to
      stimulate Th9 cell differentiation.

PMID- 22363713
TI  - The ratio and concentration of two monoterpenes mediate fecundity of the pinewood
      nematode and growth of its associated fungi.
AB  - The pinewood nematode (PWN) Bursaphelenchus xylophilus, vectored primarily by the
      sawyer beetle, Monochamus alternatus, is an important invasive pest and causal
      agent of pine wilt disease of Chinese Masson pine, Pinus massoniana. Previous
      work demonstrated that the ratios and concentrations of alpha-pinene:beta-pinene
      differed between healthy trees and those trees containing blue-stain fungus (and
      M. alternatus pupae). However, the potential influence of the altered monoterpene
      ratios and concentrations on PWN and associated fungi remained unknown. Our
      current results show that low concentrations of the monoterpenes within petri
      dishes reduced PWN propagation, whereas the highest concentration of the
      monoterpenes increased PWN propagation. The propagation rate of PWN treated with
      the monoterpene ratio representative of blue-stain infected pine (alpha
      pinene:beta-pinene = 1:0.8, 137.6 mg/ml) was significantly higher than that
      (alpha-pinene:beta-pinene = 1:0.1, 137.6 mg/ml) representative of healthy pines
      or those damaged by M. alternatus feeding, but without blue stain. Furthermore,
      inhibition of mycelial growth of associated fungi increased with the
      concentration of the monoterpenes alpha-pinene and beta-pinene. Additionally,
      higher levels of beta-pinene (alpha-pinene:beta-pinene = 1:0.8) resulted in
      greater inhibition of the growth of the associated fungi Sporothrix sp.2 and
      Ophiostoma ips strains, but had no significant effects on the growth of
      Sporothrix sp.1, which is the best food resource for PWN. These results suggest
      that host monoterpenes generally reduce the reproduction of PWN. However, PWN
      utilizes high monoterpene concentrations and native blue-stain fungus Sporothrix
      sp.1 to improve its own propagation and overcome host resistance, which may
      provide clues to understanding the ecological mechanisms of PWN's successful
      invasion.

PMID- 22363714
TI  - Population analysis of the Fusarium graminearum species complex from wheat in
      China show a shift to more aggressive isolates.
AB  - A large number of Fusarium isolates was collected from blighted wheat spikes
      originating from 175 sampling sites, covering 15 provinces in China. Species and
      trichothecene chemotype determination by multilocus genotyping (MLGT) indicated
      that F. graminearum s. str. with the 15-acetyl deoxynivalenol (15ADON) chemotype
      and F. asiaticum with either the nivalenol (NIV) or the 3-acetyl deoxynivalenol
      (3ADON) chemotype were the dominant causal agents. Bayesian model-based
      clustering with allele data obtained with 12 variable number of tandem repeats
      (VNTR) markers, detected three genetic clusters that also show distinct
      chemotypes. High levels of population genetic differentiation and low levels of
      effective number of migrants were observed between these three clusters.
      Additional genotypic analyses revealed that F. graminearum s. str. and F.
      asiaticum are sympatric. In addition, composition analysis of these clusters
      indicated a biased gene flow from 3ADON to NIV producers in F. asiaticum. In
      phenotypic analyses, F. asiaticum that produce 3ADON revealed significant
      advantages over F. asiaticum that produce NIV in pathogenicity, growth rate,
      fecundity, conidial length, trichothecene accumulation and resistance to
      benzimidazole. These results suggest that natural selection drives the spread of
      a more vigorous, more toxigenic pathogen population which also shows higher
      levels of fungicide resistance.

PMID- 22363715
TI  - Spatial pattern and determinants of the first detection locations of invasive
      alien species in mainland China.
AB  - BACKGROUND: The unintentional transport of species as a result of human
      activities has reached unprecedented rates. Once established, introduced species
      can be nearly impossible to eradicate. It is therefore essential to identify and
      monitor locations where invaders are most likely to establish new populations.
      Despite the obvious value of early detection, how does an agency identify areas
      that are most vulnerable to new invaders? Here we propose a novel approach by
      using the "first detection location" (FDL) of introduced species in China to
      quantify characteristics of areas where introduced species are first reported.
      METHODOLOGY/PRINCIPAL FINDINGS: We obtained FDLs for 166 species (primarily
      agricultural and forestry pests) that were unintentionally introduced into China
      prior to 2008 from literature searches. The spatial pattern and determinants of
      FDLs were examined at the provincial level. The spatial pattern of FDLs varied
      among provinces with more commerce and trade and economically developed provinces
      in coastal regions having more FDLs than interior provinces. For example, 74.6%
      of FDLs were distributed in coastal regions despite that they only cover 15.6% of
      the total area in China. Variables that may be indicators of "introduction
      pressure" (e.g. the amount of received commerce) had an overwhelming effect on
      the number of FDLs in each province (R(2) = 0.760). CONCLUSIONS/SIGNIFICANCE: Our
      results suggest that "introduction pressure" may be one of the most important
      factors that determine the locations where newly-introduced species are first
      detected, and that open and developed provinces in China should be prioritized
      when developing monitoring programs that focus on locating and managing new
      introductions. Our study illustrates that FDL approaches can contribute to the
      study and management of biological invasions not only for China but also for
      elsewhere.

PMID- 22363716
TI  - Neurochemical and neuroanatomical identification of central pattern generator
      neuron homologues in Nudipleura molluscs.
AB  - Certain invertebrate neurons can be identified by their behavioral functions.
      However, evolutionary divergence can cause some species to not display particular
      behaviors, thereby making it impossible to use physiological characteristics
      related to those behaviors for identifying homologous neurons across species.
      Therefore, to understand the neural basis of species-specific behavior, it is
      necessary to identify homologues using characteristics that are independent of
      physiology. In the Nudipleura mollusc Tritonia diomedea, Cerebral Neuron 2 (C2)
      was first described as being a member of the swim central pattern generator
      (CPG). Here we demonstrate that neurochemical markers, in conjunction with
      previously known neuroanatomical characteristics, allow C2 to be uniquely
      identified without the aid of electrophysiological measures. Specifically, C2 had
      three characteristics that, taken together, identified the neuron: 1) a white
      cell on the dorsal surface of the cerebral ganglion, 2) an axon that projected to
      the contralateral pedal ganglion and through the pedal commissure, and 3)
      immunoreactivity for the peptides FMRFamide and Small Cardioactive Peptide B.
      These same anatomical and neurochemical characteristics also uniquely identified
      the C2 homologue in Pleurobranchaea californica (called A1), which was previously
      identified by its analogous role in the Pleurobranchaea swim CPG. Furthermore,
      these characteristics were used to identify C2 homologues in Melibe leonina,
      Hermissenda crassicornis, and Flabellina iodinea, species that are
      phylogenetically closer to Tritonia than Pleurobranchaea, but do not display the
      same swimming behavior as Tritonia or Pleurobranchaea. These identifications will
      allow future studies comparing and contrasting the physiological properties of C2
      across species that can and cannot produce the type of swimming behavior
      exhibited by Tritonia.

PMID- 22363717
TI  - Population distribution, settlement patterns and accessibility across Africa in
      2010.
AB  - The spatial distribution of populations and settlements across a country and
      their interconnectivity and accessibility from urban areas are important for
      delivering healthcare, distributing resources and economic development. However,
      existing spatially explicit population data across Africa are generally based on
      outdated, low resolution input demographic data, and provide insufficient detail
      to quantify rural settlement patterns and, thus, accurately measure population
      concentration and accessibility. Here we outline approaches to developing a new
      high resolution population distribution dataset for Africa and analyse rural
      accessibility to population centers. Contemporary population count data were
      combined with detailed satellite-derived settlement extents to map population
      distributions across Africa at a finer spatial resolution than ever before.
      Substantial heterogeneity in settlement patterns, population concentration and
      spatial accessibility to major population centres is exhibited across the
      continent. In Africa, 90% of the population is concentrated in less than 21% of
      the land surface and the average per-person travel time to settlements of more
      than 50,000 inhabitants is around 3.5 hours, with Central and East Africa
      displaying the longest average travel times. The analyses highlight large
      inequities in access, the isolation of many rural populations and the challenges
      that exist between countries and regions in providing access to services. The
      datasets presented are freely available as part of the AfriPop project, providing
      an evidence base for guiding strategic decisions.

PMID- 22363718
TI  - Genome-wide SNP detection, validation, and development of an 8K SNP array for
      apple.
AB  - As high-throughput genetic marker screening systems are essential for a range of
      genetics studies and plant breeding applications, the International RosBREED SNP
      Consortium (IRSC) has utilized the Illumina Infinium(r) II system to develop a
      medium- to high-throughput SNP screening tool for genome-wide evaluation of
      allelic variation in apple (Malus*domestica) breeding germplasm. For genome-wide
      SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding
      germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II.
      Following alignment of these sequences to the whole genome sequence of 'Golden
      Delicious', SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were
      detected, corresponding to one SNP to every 288 bp of the genome. The Illumina
      GoldenGate(r) assay was then used to validate a subset of 144 SNPs with a range
      of characteristics, using a set of 160 apple accessions. This validation assay
      enabled fine-tuning of the final subset of SNPs for the Illumina Infinium(r) II
      system. The set of stringent filtering criteria developed allowed choice of a set
      of SNPs that not only exhibited an even distribution across the apple genome and
      a range of minor allele frequencies to ensure utility across germplasm, but also
      were located in putative exonic regions to maximize genotyping success rate. A
      total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of
      which 5554 were polymorphic after evaluation in segregating families and a
      germplasm collection. This publicly available genomics resource will provide an
      unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait
      association discovery, description of the genetic architecture of quantitative
      traits, investigation of genetic variation (neutral and functional), and genomic
      selection in apple.

PMID- 22363719
TI  - Evaluation of brain iron content based on magnetic resonance imaging (MRI):
      comparison among phase value, R2* and magnitude signal intensity.
AB  - BACKGROUND AND PURPOSE: Several magnetic resonance imaging (MRI) techniques are
      being exploited to measure brain iron levels increasingly as iron deposition has
      been implicated in some neurodegenerative diseases. However, there remains no
      unified evaluation of these methods as postmortem measurement isn't commonly
      available as the reference standard. The purpose of this study was to make a
      comparison among these methods and try to find a new index of brain iron.
      METHODS: We measured both phase values and R2* in twenty-four adults, and
      performed correlation analysis among the two methods and the previously published
      iron concentrations. We also proposed a new method using magnitude signal
      intensity and compared it with R2* and brain iron. RESULTS: We found phase value
      correlated with R2* in substantia nigra (r = -0.723, p<0.001) and putamen (r = 
      0.514, p = 0.010), while no correlations in red nucleus (r = -0.236, p = 0.268)
      and globus pallidus (r = -0.111, p = 0.605). And the new magnitude method had
      significant correlations in red nucleus (r = -0.593, p = 0.002), substantia nigra
      (r = -0.521, p = 0.009), globus pallidus (r = -0.750, p<0.001) and putamen (r = 
      0.547, p = 0.006) with R2*. A strong inverse correlation was also found between
      the new magnitude method and previously published iron concentrations in seven
      brain regions (r = -0.982, P<0.001). CONCLUSIONS: Our study indicates that phase
      value may not be used for assessing the iron content in some brain regions
      especially globus pallidus. The new magnitude method is highly consistent with
      R2* especially in globus pallidus, and we assume that this approach may be
      acceptable as an index of iron content in iron-rich brain regions.

PMID- 22363720
TI  - Molecular identification of rickettsial endosymbionts in the non-phagotrophic
      volvocalean green algae.
AB  - BACKGROUND: The order Rickettsiales comprises gram-negative obligate
      intracellular bacteria (also called rickettsias) that are mainly associated with
      arthropod hosts. This group is medically important because it contains human
      pathogenic species that cause dangerous diseases. Until now, there has been no
      report of non-phagotrophic photosynthetic eukaryotes, such as green plants,
      harboring rickettsias. METHODOLOGY/PRINCIPAL FINDINGS: We examined the bacterial
      endosymbionts of two freshwater volvocalean green algae: unicellular Carteria
      cerasiformis and colonial Pleodorina japonica. Epifluorescence microscopy using
      4'-6-deamidino-2-phenylindole staining revealed the presence of endosymbionts in
      all C. cerasiformis NIES-425 cells, and demonstrated a positive correlation
      between host cell size and the number of endosymbionts. Strains both containing
      and lacking endosymbionts of C. cerasiformis (NIES-425 and NIES-424) showed a >10
      fold increase in cell number and typical sigmoid growth curves over 192 h. A
      phylogenetic analysis of 16 S ribosomal (r)RNA gene sequences from the
      endosymbionts of C. cerasiformis and P. japonica demonstrated that they formed a
      robust clade (hydra group) with endosymbionts of various non-arthropod hosts
      within the family Rickettsiaceae. There were significantly fewer differences in
      the 16 S rRNA sequences of the rickettsiacean endosymbionts between C.
      cerasiformis and P. japonica than in the chloroplast 16 S rRNA or 18 S rRNA of
      the host volvocalean cells. Fluorescence in situ hybridization demonstrated the
      existence of the rickettsiacean endosymbionts in the cytoplasm of two volvocalean
      species. CONCLUSIONS/SIGNIFICANCE: The rickettsiacean endosymbionts are likely
      not harmful to their volvocalean hosts and may have been recently transmitted
      from other non-arthropod organisms. Because rickettsias are the closest relatives
      of mitochondria, incipient stages of mitochondrial endosymbiosis may be deduced
      using both strains with and without C. cerasiformis endosymbionts.

PMID- 22363721
TI  - Defensome against toxic diatom aldehydes in the sea urchin Paracentrotus lividus.
AB  - Many diatom species produce polyunsaturated aldehydes, such as decadienal, which
      compromise embryonic and larval development in benthic organisms. Here newly
      fertilized Paracentrotus lividus sea urchins were exposed to low concentration of
      decadienal and the expression levels of sixteen genes, implicated in a broad
      range of functional responses, were followed by Real Time qPCR in order to
      identify potential decadienal targets. We show that at low decadienal
      concentrations the sea urchin Paracentrotus lividus places in motion different
      classes of genes to defend itself against this toxic aldehyde, activating hsp60
      and two proteases, hat and BP10, at the blastula stage and hsp56 and several
      other genes (14-3-3epsilon, p38 MAPK, MTase, and GS) at the prism stage. At this
      latter stage all genes involved in skeletogenesis (Nec, uni, SM50 and SM30) were
      also down-expressed, following developmental abnormalities that mainly affected
      skeleton morphogenesis. Moreover, sea urchin embryos treated with increasing
      concentrations of decadienal revealed a dose-dependent response of activated
      target genes. Finally, we suggest that this orchestrated defense system against
      decadienal represents part of the chemical defensome of P. lividus affording
      protection from environmental toxicants.

PMID- 22363722
TI  - Cellular prion protein expression is not regulated by the Alzheimer's amyloid
      precursor protein intracellular domain.
AB  - There is increasing evidence of molecular and cellular links between Alzheimer's
      disease (AD) and prion diseases. The cellular prion protein, PrP(C), modulates
      the post-translational processing of the AD amyloid precursor protein (APP),
      through its inhibition of the beta-secretase BACE1, and oligomers of amyloid-beta
      bind to PrP(C) which may mediate amyloid-beta neurotoxicity. In addition, the APP
      intracellular domain (AICD), which acts as a transcriptional regulator, has been
      reported to control the expression of PrP(C). Through the use of transgenic mice,
      cell culture models and manipulation of APP expression and processing, this study
      aimed to clarify the role of AICD in regulating PrP(C). Over-expression of the
      three major isoforms of human APP (APP(695), APP(751) and APP(770)) in cultured
      neuronal and non-neuronal cells had no effect on the level of endogenous PrP(C).
      Furthermore, analysis of brain tissue from transgenic mice over-expressing either
      wild type or familial AD associated mutant human APP revealed unaltered PrP(C)
      levels. Knockdown of endogenous APP expression in cells by siRNA or inhibition of
      gamma-secretase activity also had no effect on PrP(C) levels. Overall, we did not
      detect any significant difference in the expression of PrP(C) in any of the cell
      or animal-based paradigms considered, indicating that the control of cellular
      PrP(C) levels by AICD is not as straightforward as previously suggested.

PMID- 22363723
TI  - Delivery of iron-sulfur clusters to the hydrogen-oxidizing [NiFe]-hydrogenases in
      Escherichia coli requires the A-type carrier proteins ErpA and IscA.
AB  - During anaerobic growth Escherichia coli synthesizes two membrane-associated
      hydrogen-oxidizing [NiFe]-hydrogenases, termed hydrogenase 1 and hydrogenase 2.
      Each enzyme comprises a catalytic subunit containing the [NiFe] cofactor, an
      electron-transferring small subunit with a particular complement of [Fe-S] (iron
      sulfur) clusters and a membrane-anchor subunit. How the [Fe-S] clusters are
      delivered to the small subunit of these enzymes is unclear. A-type carrier (ATC)
      proteins of the Isc (iron-sulfur-cluster) and Suf (sulfur mobilization) [Fe-S]
      cluster biogenesis pathways are proposed to traffic pre-formed [Fe-S] clusters to
      apoprotein targets. Mutants that could not synthesize SufA had active hydrogenase
      1 and hydrogenase 2 enzymes, thus demonstrating that the Suf machinery is not
      required for hydrogenase maturation. In contrast, mutants devoid of the IscA,
      ErpA or IscU proteins of the Isc machinery had no detectable hydrogenase 1 or 2
      activities. Lack of activity of both enzymes correlated with the absence of the
      respective [Fe-S]-cluster-containing small subunit, which was apparently rapidly
      degraded. During biosynthesis the hydrogenase large subunits receive their [NiFe]
      cofactor from the Hyp maturation machinery. Subsequent to cofactor insertion a
      specific C-terminal processing step occurs before association of the large
      subunit with the small subunit. This processing step is independent of small
      subunit maturation. Using western blotting experiments it could be shown that
      although the amount of each hydrogenase large subunit was strongly reduced in the
      iscA and erpA mutants, some maturation of the large subunit still occurred.
      Moreover, in contrast to the situation in Isc-proficient strains, these processed
      large subunits were not membrane-associated. Taken together, our findings
      demonstrate that both IscA and ErpA are required for [Fe-S] cluster delivery to
      the small subunits of the hydrogen-oxidizing hydrogenases; however, delivery of
      the Fe atom to the active site might have different requirements.

PMID- 22363724
TI  - Population-level metrics of trophic structure based on stable isotopes and their
      application to invasion ecology.
AB  - Biological invasions are a significant driver of human-induced global change and
      many ecosystems sustain sympatric invaders. Interactions occurring among these
      invaders have important implications for ecosystem structure and functioning, yet
      they are poorly understood. Here we apply newly developed metrics derived from
      stable isotope data to provide quantitative measures of trophic diversity within
      populations or species. We then use these to test the hypothesis that sympatric
      invaders belonging to the same functional feeding group occupy a smaller isotopic
      niche than their allopatric counterparts. Two introduced, globally important,
      benthic omnivores, Louisiana swamp crayfish (Procambarus clarkii) and carp
      (Cyprinus carpio), are sympatric in Lake Naivasha, Kenya. We applied our metrics
      to an 8-year data set encompassing the establishment of carp in the lake. We
      found a strong asymmetric interaction between the two invasive populations, as
      indicated by inverse correlations between carp abundance and measures of crayfish
      trophic diversity. Lack of isotopic niche overlap between carp and crayfish in
      the majority of years indicated a predominantly indirect interaction. We suggest
      that carp-induced habitat alteration reduced the diversity of crayfish prey,
      resulting in a reduction in the dietary niche of crayfish. Stable isotopes
      provide an integrated signal of diet over space and time, offering an appropriate
      scale for the study of population niches, but few isotope studies have retained
      the often insightful information revealed by variability among individuals in
      isotope values. Our population metrics incorporate such variation, are robust to
      the vagaries of sample size and are a useful additional tool to reveal subtle
      dietary interactions among species. Although we have demonstrated their
      applicability specifically using a detailed temporal dataset of species invasion
      in a lake, they have a wide array of potential ecological applications.

PMID- 22363725
TI  - Sprouted innervation into uterine transplants contributes to the development of
      hyperalgesia in a rat model of endometriosis.
AB  - Endometriosis is an enigmatic painful disorder whose pain symptoms remain
      difficult to alleviate in large part because the disorder is defined by
      extrauteral endometrial growths whose contribution to pain is poorly understood.
      A rat model (ENDO) involves autotransplanting on abdominal arteries uterine
      segments that grow into vascularized cysts that become innervated with sensory
      and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used
      behavioral, physiological, and immunohistochemical methods to test the hypothesis
      that cyst innervation contributes to the development of this hyperalgesia after
      transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts
      at two weeks, sprouted further and more densely into the cyst wall by four weeks,
      and matured by six weeks post-transplant. Sensory fibers became abnormally
      functionally active between two and three weeks post-transplant, remaining active
      thereafter. Vaginal hyperalgesia became significant between four and five weeks
      post-transplant, and stabilized after six to eight weeks. Removing cysts before
      they acquired functional innervation prevented vaginal hyperalgesia from
      developing, whereas sham cyst removal did not. Thus, abnormally-active
      innervation of ectopic growths occurs before hyperalgesia develops, supporting
      the hypothesis. These findings suggest that painful endometriosis can be
      classified as a mixed inflammatory/neuropathic pain condition, which opens new
      avenues for pain relief. The findings also have implications beyond endometriosis
      by suggesting that functionality of any transplanted tissue can be influenced by
      the innervation it acquires.

PMID- 22363727
TI  - The importance of craniofacial sutures in biomechanical finite element models of
      the domestic pig.
AB  - Craniofacial sutures are a ubiquitous feature of the vertebrate skull. Previous
      experimental work has shown that bone strain magnitudes and orientations often
      vary when moving from one bone to another, across a craniofacial suture. This has
      led to the hypothesis that craniofacial sutures act to modify the strain
      environment of the skull, possibly as a mode of dissipating high stresses
      generated during feeding or impact. This study tests the hypothesis that the
      introduction of craniofacial sutures into finite element (FE) models of a modern
      domestic pig skull would improve model accuracy compared to a model without
      sutures. This allowed the mechanical effects of sutures to be assessed in
      isolation from other confounding variables. These models were also validated
      against strain gauge data collected from the same specimen ex vivo. The
      experimental strain data showed notable strain differences between adjacent
      bones, but this effect was generally not observed in either model. It was found
      that the inclusion of sutures in finite element models affected strain
      magnitudes, ratios, orientations and contour patterns, yet contrary to
      expectations, this did not improve the fit of the model to the experimental data,
      but resulted in a model that was less accurate. It is demonstrated that the
      presence or absence of sutures alone is not responsible for the inaccuracies in
      model strain, and is suggested that variations in local bone material properties,
      which were not accounted for by the FE models, could instead be responsible for
      the pattern of results.

PMID- 22363726
TI  - The Gac-Rsm and SadB signal transduction pathways converge on AlgU to
      downregulate motility in Pseudomonas fluorescens.
AB  - Flagella mediated motility in Pseudomonas fluorescens F113 is tightly regulated.
      We have previously shown that motility is repressed by the GacA/GacS system and
      by SadB through downregulation of the fleQ gene, encoding the master regulator of
      the synthesis of flagellar components, including the flagellin FliC. Here we show
      that both regulatory pathways converge in the regulation of transcription and
      possibly translation of the algU gene, which encodes a sigma factor. AlgU is
      required for multiple functions, including the expression of the amrZ gene which
      encodes a transcriptional repressor of fleQ. Gac regulation of algU occurs during
      exponential growth and is exerted through the RNA binding proteins RsmA and RsmE
      but not RsmI. RNA immunoprecipitation assays have shown that the RsmA protein
      binds to a polycistronic mRNA encoding algU, mucA, mucB and mucD, resulting in
      lower levels of algU. We propose a model for repression of the synthesis of the
      flagellar apparatus linking extracellular and intracellular signalling with the
      levels of AlgU and a new physiological role for the Gac system in the
      downregulation of flagella biosynthesis during exponential growth.

PMID- 22363728
TI  - Plasma hormones facilitated the hypermotility of the colon in a chronic stress
      rat model.
AB  - OBJECTIVE: To study the relationship between brain-gut peptides, gastrointestinal
      hormones and altered motility in a rat model of repetitive water avoidance stress
      (WAS), which mimics the irritable bowel syndrome (IBS). METHODS: Male Wistar rats
      were submitted daily to 1-h of water avoidance stress (WAS) or sham WAS (SWAS)
      for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay
      Kits. Proximal colonic smooth muscle (PCSM) contractions were studied in an organ
      bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca
      were recorded by the patch-clamp technique. RESULTS: The number of fecal pellets
      during 1 h of acute restraint stress and the plasma hormones levels of substance
      P (SP), thyrotropin-releasing hormone (TRH), motilin (MTL), and cholecystokinin
      (CCK) in WAS rats were significantly increased compared with SWAS rats, whereas
      vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and
      corticotropin releasing hormone (CRH) in WAS rats were not significantly changed
      and peptide YY (PYY) in WAS rats was significantly decreased. Likewise, the
      amplitudes of spontaneous contractions of PCSM in WAS rats were significantly
      increased comparing with SWAS rats. The plasma of WAS rats (100 ul) decreased the
      amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs
      were significantly decreased in WAS rats compared with SWAS rats and the plasma
      of WAS rats (100 ul) increased the amplitude of IKv and IBKCa in normal rats.
      CONCLUSION: These results suggest that WAS leads to changes of plasma hormones
      levels and to disordered myogenic colonic motility in the short term, but that
      the colon rapidly establishes a new equilibrium to maintain the normal baseline
      functioning.

PMID- 22363729
TI  - Optical tweezers as a new biomedical tool to measure zeta potential of stored red
      blood cells.
AB  - During storage, red blood cells (RBCs) for transfusion purposes suffer
      progressive deterioration. Sialylated glycoproteins of the RBC membrane are
      responsible for a negatively charged surface which creates a repulsive electrical
      zeta potential. These charges help prevent the interaction between RBCs and other
      cells, and especially among each RBCs. Reports in the literature have stated that
      RBCs sialylated glycoproteins can be sensitive to enzymes released by leukocyte
      degranulation. Thus, the aim of this study was, by using an optical tweezers as a
      biomedical tool, to measure the zeta potential in standard RBCs units and in
      leukocyte reduced RBC units (collected in CPD-SAGM) during storage. Optical
      tweezers is a sensitive tool that uses light for measuring cell biophysical
      properties which are important for clinical and research purposes. This is the
      first study to analyze RBCs membrane charges during storage. In addition, we
      herein also measured the elasticity of RBCs also collected in CPD-SAGM. In
      conclusion, the zeta potential decreased 42% and cells were 134% less deformable
      at the end of storage. The zeta potential from leukodepleted units had a similar
      profile when compared to units stored without leukoreduction, indicating that
      leukocyte lyses were not responsible for the zeta potential decay. Flow cytometry
      measurements of reactive oxygen species suggested that this decay is due to
      membrane oxidative damages. These results show that measurements of zeta
      potentials provide new insights about RBCs storage lesion for transfusion
      purposes.

PMID- 22363730
TI  - Peritoneal dialysis-related peritonitis due to Staphylococcus aureus: a single
      center experience over 15 years.
AB  - Peritonitis caused by Staphylococcus aureus is a serious complication of
      peritoneal dialysis (PD), which is associated with poor outcome and high PD
      failure rates. We reviewed the records of 62 S. aureus peritonitis episodes that
      occurred between 1996 and 2010 in the dialysis unit of a single university
      hospital and evaluated the host and bacterial factors influencing peritonitis
      outcome. Peritonitis incidence was calculated for three subsequent 5-year periods
      and compared using a Poisson regression model. The production of biofilm,
      enzymes, and toxins was evaluated. Oxacillin resistance was evaluated based on
      minimum inhibitory concentration and presence of the mecA gene. Logistic
      regression was used for the analysis of demographic, clinical, and
      microbiological factors influencing peritonitis outcome. Resolution and death
      rates were compared with 117 contemporary coagulase-negative staphylococcus
      (CoNS) episodes. The incidence of S. aureus peritonitis declined significantly
      over time from 0.13 in 1996-2000 to 0.04 episodes/patient/year in 2006-2010 (p =
      0.03). The oxacillin resistance rate was 11.3%. Toxin and enzyme production was
      expressive, except for enterotoxin D. Biofilm production was positive in 88.7% of
      strains. The presence of the mecA gene was associated with a higher frequency of
      fever and abdominal pain. The logistic regression model showed that diabetes
      mellitus (p = 0.009) and beta-hemolysin production (p = 0.006) were independent
      predictors of non-resolution of infection. The probability of resolution was
      higher among patients aged 41 to 60 years than among those >60 years (p = 0.02).
      A trend to higher death rate was observed for S. aureus episodes (9.7%) compared
      to CoNS episodes (2.5%), (p = 0.08), whereas resolution rates were similar.
      Despite the decline in incidence, S. aureus peritonitis remains a serious
      complication of PD that is associated with a high death rate. The outcome of this
      infection is negatively influenced by host factors such as age and diabetes
      mellitus. In addition, beta-hemolysin production is predictive of non-resolution
      of infection, suggesting a pathogenic role of this factor in PD-related S. aureus
      peritonitis.

PMID- 22363731
TI  - 3,3'-Diindolylmethane exhibits antileukemic activity in vitro and in vivo through
      a Akt-dependent process.
AB  - 3,3'-Diindolylmethane (DIM), one of the active products derived from Brassica
      plants, is a promising antitumor agent. The present study indicated that DIM
      significantly induced apoptosis in U937 human leukemia cells in dose- and time
      dependent manners. These events were also noted in other human leukemia cells
      (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone
      marrow mononuclear cells. We also found that DIM-induced lethality is associated
      with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation,
      p21(cip1/waf1) up-regulation, and Akt inactivation accompanied by c-jun NH2
      terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively
      active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down
      regulation, JNK activation, and apoptosis. Conversely, DIM lethality was
      potentiated by the PI3K inhibitor LY294002. Interruption of the JNK pathway by
      pharmacologic or genetic approaches attenuated DIM-induced caspases activation,
      Mcl-1 down-regulation, and apoptosis. Lastly, DIM inhibits tumor growth of mouse
      U937 xenograft, which was related to induction of apoptosis and inactivation of
      Akt, as well as activation of JNK. Collectively, these findings suggest that DIM
      induces apoptosis in human leukemia cell lines and primary human leukemia cells,
      and exhibits antileukemic activity in vivo through Akt inactivation and JNK
      activation.

PMID- 22363732
TI  - Lymphocyte subsets show different response patterns to in vivo bound natalizumab-
      a flow cytometric study on patients with multiple sclerosis.
AB  - Natalizumab is an effective monoclonal antibody therapy for the treatment of
      relapsing-remitting multiple sclerosis (RRMS) and interferes with immune cell
      migration into the central nervous system by blocking the alpha(4) subunit of
      very-late activation antigen-4 (VLA-4). Although well tolerated and very
      effective, some patients still suffer from relapses in spite of natalizumab
      therapy or from unwanted side effects like progressive multifocal
      leukoencephalopathy (PML). In search of a routine-qualified biomarker on the
      effectiveness of natalizumab therapy we applied flow cytometry and analyzed
      natalizumab binding to alpha(4) and alpha(4) integrin surface levels on T-cells,
      B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up
      to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a
      significant and sustained increase of lymphocyte-bound natalizumab (p<0.001)
      which was paralleled by a significant decrease in detectability of the alpha(4)
      integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced
      natalizumab accumulations on T and B cells at single measurements in all patients
      who reported clinical disease activity (n = 4). The natalizumab binding capacity
      of in vitro saturated lymphocytes collected during therapy was strongly
      diminished compared to treatment-naive cells indicating a therapy-induced
      reduction of alpha(4). Summing up, this pilot study shows that flow cytometry is
      a useful method to monitor natalizumab binding to lymphocytes from RRMS patients
      under therapy. Investigating natalizumab binding provides an opportunity to
      evaluate the molecular level of effectiveness of natalizumab therapy in
      individual patients. In combination with natalizumab saturation experiments, it
      possibly even provides a means of studying the feasability of patient-tailored
      infusion intervals. A routine-qualified biomarker on the basis of individual
      natalizumab saturation on lymphocyte subsets might be an effective tool to
      improve treatment safety.

PMID- 22363733
TI  - PrionHome: a database of prions and other sequences relevant to prion phenomena.
AB  - Prions are units of propagation of an altered state of a protein or proteins;
      prions can propagate from organism to organism, through cooption of other protein
      copies. Prions contain no necessary nucleic acids, and are important both as both
      pathogenic agents, and as a potential force in epigenetic phenomena. The original
      prions were derived from a misfolded form of the mammalian Prion Protein PrP.
      Infection by these prions causes neurodegenerative diseases. Other prions cause
      non-Mendelian inheritance in budding yeast, and sometimes act as diseases of
      yeast. We report the bioinformatic construction of the PrionHome, a database of
      >2000 prion-related sequences. The data was collated from various public and
      private resources and filtered for redundancy. The data was then processed
      according to a transparent classification system of prionogenic sequences (i.e.,
      sequences that can make prions), prionoids (i.e., proteins that propagate like
      prions between individual cells), and other prion-related phenomena. There are
      eight PrionHome classifications for sequences. The first four classifications are
      derived from experimental observations: prionogenic sequences, prionoids, other
      prion-related phenomena, and prion interactors. The second four classifications
      are derived from sequence analysis: orthologs, paralogs, pseudogenes, and
      candidate-prionogenic sequences. Database entries list: supporting information
      for PrionHome classifications, prion-determinant areas (where relevant), and
      disordered and compositionally-biased regions. Also included are literature
      references for the PrionHome classifications, transcripts and genomic
      coordinates, and structural data (including comparative models made for the
      PrionHome from manually curated alignments). We provide database usage examples
      for both vertebrate and fungal prion contexts. Using the database data, we have
      performed a detailed analysis of the compositional biases in known budding-yeast
      prionogenic sequences, showing that the only abundant bias pattern is for
      asparagine bias with subsidiary serine bias. We anticipate that this database
      will be a useful experimental aid and reference resource. It is freely available
      at: http://libaio.biol.mcgill.ca/prion.

PMID- 22363734
TI  - Identification of a novel gene product that promotes survival of Mycobacterium
      smegmatis in macrophages.
AB  - BACKGROUND: Bacteria of the suborder Corynebacterineae include significant human
      pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in
      mycobacteria is increasingly common making identification of new antimicrobials a
      priority. Mycobacteria replicate intracellularly, most commonly within the
      phagosomes of macrophages, and bacterial proteins essential for intracellular
      survival and persistence are particularly attractive targets for intervention
      with new generations of anti-mycobacterial drugs. METHODOLOGY/PRINCIPAL FINDINGS:
      We have identified a novel gene that, when inactivated, leads to accelerated
      death of M. smegmatis within a macrophage cell line in the first eight hours
      following infection. Complementation of the mutant with an intact copy of the
      gene restored survival to near wild type levels. Gene disruption did not affect
      growth compared to wild type M. smegmatis in axenic culture or in the presence of
      low pH or reactive oxygen intermediates, suggesting the growth defect is not
      related to increased susceptibility to these stresses. The disrupted gene,
      MSMEG_5817, is conserved in all mycobacteria for which genome sequence
      information is available, and designated Rv0807 in M. tuberculosis. Although
      homology searches suggest that MSMEG_5817 is similar to the serine:pyruvate
      aminotransferase of Brevibacterium linens suggesting a possible role in
      glyoxylate metabolism, enzymatic assays comparing activity in wild type and
      mutant strains demonstrated no differences in the capacity to metabolize
      glyoxylate. CONCLUSIONS/SIGNIFICANCE: MSMEG_5817 is a previously uncharacterized
      gene that facilitates intracellular survival of mycobacteria. Interference with
      the function of MSMEG_5817 may provide a novel therapeutic approach for control
      of mycobacterial pathogens by assisting the host immune system in clearance of
      persistent intracellular bacteria.

PMID- 22363735
TI  - Direct imaging of RAB27B-enriched secretory vesicle biogenesis in lacrimal acinar
      cells reveals origins on a nascent vesicle budding site.
AB  - This study uses YFP-tagged Rab27b expression in rabbit lacrimal gland acinar
      cells, which are polarized secretory epithelial cells, to characterize early
      stages of secretory vesicle trafficking. Here we demonstrate the utility of YFP
      Rab27b to delineate new perspectives on the mechanisms of early vesicle
      biogenesis in lacrimal gland acinar cells, where information is significantly
      limited. Protocols were developed to deplete the mature YFP-Rab27b-enriched
      secretory vesicle pool in the subapical region of the cell, and confocal
      fluorescence microscopy was used to track vesicle replenishment. This analysis
      revealed a basally-localized organelle, which we termed the "nascent vesicle
      site," from which nascent vesicles appeared to emerge. Subapical vesicular YFP
      Rab27b was co-localized with p150(Glued), a component of the dynactin cofactor of
      cytoplasmic dynein. Treatment with the microtubule-targeted agent, nocodazole,
      did not affect release of mature secretory vesicles, although during vesicle
      repletion it significantly altered nascent YFP-Rab27b-enriched secretory vesicle
      localization. Instead of moving to the subapical region, these vesicles were
      trapped at the nascent vesicle site which was adjacent to, if not a sub
      compartment of, the trans-Golgi network. Finally, YFP-Rab27b-enriched secretory
      vesicles which reached the subapical cytoplasm appeared to acquire the actin
      based motor protein, Myosin 5C. Our findings show that Rab27b enrichment occurs
      early in secretory vesicle formation, that secretory vesicles bud from a visually
      discernable nascent vesicle site, and that transport from the nascent vesicle
      site to the subapical region requires intact microtubules.

PMID- 22363736
TI  - Acaricide residues in laying hens naturally infested by red mite Dermanyssus
      gallinae.
AB  - In the poultry industry, control of the red mite D. gallinae primarily relies
      worldwide on acaricides registered for use in agriculture or for livestock, and
      those most widely used are carbamates, followed by amidines, pyrethroids and
      organophosphates. Due to the repeated use of acaricides--sometimes in high
      concentrations--to control infestation, red mites may become resistant, and
      acaricides may accumulate in chicken organs and tissues, and also in eggs. To
      highlight some situations of misuse/abuse of chemicals and of risk to human
      health, we investigated laying hens, destined to the slaughterhouse, for the
      presence of acaricide residues in their organs and tissues. We used 45 hens from
      which we collected a total of 225 samples from the following tissues and organs:
      skin, fat, liver, muscle, hearth, and kidney. In these samples we analyzed the
      residual contents of carbaryl and permethrin by LC-MS/MS.Ninety-one (40.4%)
      samples were positive to carbaryl and four samples (1.7%) were positive to
      permethrin. Concentrations of carbaryl exceeding the detection limit (0.005 ppm)
      were registered in the skin and fat of birds from two farms (p<0.01), although
      these concentrations remained below the maximum residue limit (MRLs) (0.05 ppm)
      (p<0.01). All organs/tissues of hens from a third farm were significantly more
      contaminated, with skin and muscle samples exceeding the MRL (0.05 ppm) (p<0.01)
      of carbaryl in force before its use was banned. Out of 45 chickens tested, 37
      (82.2%) were found to be contaminated by carbaryl, and 4 (8.8%) by permethrin.
      The present study is the first report on the presence of pesticides banned by the
      EU (carbaryl) or not licensed for use (permethrin) in the organs and tissues of
      laying hens, which have been treated against red mites, and then slaughtered for
      human consumption at the end of their life cycle.

PMID- 22363737
TI  - Independent recruitment of a flavin-dependent monooxygenase for safe accumulation
      of sequestered pyrrolizidine alkaloids in grasshoppers and moths.
AB  - Several insect lineages have developed diverse strategies to sequester toxic
      pyrrolizidine alkaloids from food-plants for their own defense. Here, we show
      that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the
      holometabolous butterflies, an almost identical strategy evolved independently
      for safe accumulation of pyrrolizidine alkaloids. This strategy involves a
      pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to
      their respective N-oxide, enabling the insects to avoid high concentrations of
      toxic pyrrolizidine alkaloids in the hemolymph. We have identified a
      pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of
      the grasshopper Zonocerus variegatus. After heterologous expression in E. coli,
      this enzyme shows high specificity for pyrrolizidine alkaloids of various
      structural types and for the tropane alkaloid atropine as substrates, a property
      that has been described previously for a pyrrolizidine alkaloid N-oxygenase of
      the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin
      dependent monooxygenase sequences suggest that independent gene duplication
      events preceded the establishment of this specific enzyme in the lineages of the
      grasshoppers and of arctiid moths. Two further flavin-dependent monooxygenase
      sequences have been identified from Z. variegatus sharing amino acid identities
      of approximately 78% to the pyrrolizidine alkaloid N-oxygenase. After
      heterologous expression, both enzymes are also able to catalyze the N-oxygenation
      of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With
      respect to the high sequence identity between the three Z. variegatus sequences
      this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict of
      a former bifunctional ancestor gene of which one of the gene copies optimized
      this activity for the specific adaptation to pyrrolizidine alkaloid containing
      food plants.

PMID- 22363738
TI  - The presence of the iron-sulfur motif is important for the conformational
      stability of the antiviral protein, Viperin.
AB  - Viperin, an antiviral protein, has been shown to contain a CX(3)CX(2)C motif,
      which is conserved in the radical S-adenosyl-methionine (SAM) enzyme family. A
      triple mutant which replaces these three cysteines with alanines has been shown
      to have severe deficiency in antiviral activity. Since the crystal structure of
      Viperin is not available, we have used a combination of computational methods
      including multi-template homology modeling and molecular dynamics simulation to
      develop a low-resolution predicted structure. The results show that Viperin is an
      alpha-beta protein containing iron-sulfur cluster at the center pocket. The
      calculations suggest that the removal of iron-sulfur cluster would lead to
      collapse of the protein tertiary structure. To verify these predictions, we have
      prepared, expressed and purified four mutant proteins. In three mutants
      individual cysteine residues were replaced by alanine residues while in the
      fourth all the cysteines were replaced by alanines. Conformational analyses using
      circular dichroism and steady state fluorescence spectroscopy indicate that the
      mutant proteins are partially unfolded, conformationally unstable and aggregation
      prone. The lack of conformational stability of the mutant proteins may have
      direct relevance to the absence of their antiviral activity.

PMID- 22363739
TI  - Health system resource gaps and associated mortality from pandemic influenza
      across six Asian territories.
AB  - BACKGROUND: Southeast Asia has been the focus of considerable investment in
      pandemic influenza preparedness. Given the wide variation in socio-economic
      conditions, health system capacity across the region is likely to impact to
      varying degrees on pandemic mitigation operations. We aimed to estimate and
      compare the resource gaps, and potential mortalities associated with those gaps,
      for responding to pandemic influenza within and between six territories in Asia.
      METHODS AND FINDINGS: We collected health system resource data from Cambodia,
      Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a
      mathematical transmission model to simulate a "mild-to-moderate" pandemic
      influenza scenario to estimate resource needs, gaps, and attributable mortalities
      at province level within each territory. The results show that wide variations
      exist in resource capacities between and within the six territories, with
      substantial mortalities predicted as a result of resource gaps (referred to here
      as "avoidable" mortalities), particularly in poorer areas. Severe nationwide
      shortages of mechanical ventilators were estimated to be a major cause of
      avoidable mortalities in all territories except Taiwan. Other resources
      (oseltamivir, hospital beds and human resources) are inequitably distributed
      within countries. Estimates of resource gaps and avoidable mortalities were
      highly sensitive to model parameters defining the transmissibility and clinical
      severity of the pandemic scenario. However, geographic patterns observed within
      and across territories remained similar for the range of parameter values
      explored. CONCLUSIONS: The findings have important implications for where (both
      geographically and in terms of which resource types) investment is most needed,
      and the potential impact of resource mobilization for mitigating the disease
      burden of an influenza pandemic. Effective mobilization of resources across
      administrative boundaries could go some way towards minimizing avoidable deaths.

PMID- 22363740
TI  - Liver-specific expression of transcriptionally active SREBP-1c is associated with
      fatty liver and increased visceral fat mass.
AB  - The pathogenesis of fatty liver is not understood in detail, but lipid overflow
      as well as de novo lipogenesis (DNL) seem to be the key points of hepatocyte
      accumulation of lipids. One key transcription factor in DNL is sterol regulatory
      element-binding protein (SREBP)-1c. We generated mice with liver-specific over
      expression of mature human SREBP-1c under control of the albumin promoter and a
      liver-specific enhancer (alb-SREBP-1c) to analyze systemic perturbations caused
      by this distinct alteration. SREBP-1c targets specific genes and causes key
      enzymes in DNL and lipid metabolism to be up-regulated. The alb-SREBP-1c mice
      developed hepatic lipid accumulation featuring a fatty liver by the age of 24
      weeks under normocaloric nutrition. On a molecular level, clinical parameters and
      lipid-profiles varied according to the fatty liver phenotype. The desaturation
      index was increased compared to wild type mice. In liver, fatty acids (FA) were
      increased by 50% (p<0.01) and lipid composition was shifted to mono unsaturated
      FA, whereas lipid profile in adipose tissue or serum was not altered. Serum
      analyses revealed a ~2-fold (p<0.01) increase in triglycerides and free fatty
      acids, and a ~3-fold (p<0.01) increase in insulin levels, indicating insulin
      resistance; however, no significant cytokine profile alterations have been
      determined. Interestingly and unexpectedly, mice also developed adipositas with
      considerably increased visceral adipose tissue, although calorie intake was not
      different compared to control mice. In conclusion, the alb-SREBP-1c mouse model
      allowed the elucidation of the systemic impact of SREBP-1c as a central regulator
      of lipid metabolism in vivo and also demonstrated that the liver is a more active
      player in metabolic diseases such as visceral obesity and insulin resistance.

PMID- 22363741
TI  - M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic
      beta-cells through modulation of respiratory chain activity.
AB  - Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations
      contributes to multiple diseases such as metabolic myopathies, neurodegenerative
      disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated
      1,500 mitochondrial proteins has been identified, and the function of most of
      these proteins remains to be determined. Here, we characterize the function of
      M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic beta-cells.
      We have identified a 13-long amino acid sequence located at the N-terminus of M19
      that targets the protein to mitochondria. Furthermore, using RNA interference and
      over-expression strategies, we demonstrate that M19 modulates mitochondrial
      oxygen consumption and ATP production, and could therefore regulate the
      respiratory chain activity. In an effort to determine whether M19 could play a
      role in the regulation of various cell activities, we show that this nucleoid
      protein, probably through its modulation of mitochondrial ATP production, acts on
      late muscle differentiation in myogenic C2C12 cells, and plays a permissive role
      on insulin secretion under basal glucose conditions in INS-1 pancreatic beta
      cells. Our results are therefore establishing a functional link between a
      mitochondrial nucleoid protein and the modulation of respiratory chain activities
      leading to the regulation of major cellular processes such as myogenesis and
      insulin secretion.

PMID- 22363742
TI  - Comparison of pathway analysis approaches using lung cancer GWAS data sets.
AB  - Pathway analysis has been proposed as a complement to single SNP analyses in
      GWAS. This study compared pathway analysis methods using two lung cancer GWAS
      data sets based on four studies: one a combined data set from Central Europe and
      Toronto (CETO); the other a combined data set from Germany and MD Anderson
      (GRMD). We searched the literature for pathway analysis methods that were widely
      used, representative of other methods, and had available software for performing
      analysis. We selected the programs EASE, which uses a modified Fishers Exact
      calculation to test for pathway associations, GenGen (a version of Gene Set
      Enrichment Analysis (GSEA)), which uses a Kolmogorov-Smirnov-like running sum
      statistic as the test statistic, and SLAT, which uses a p-value combination
      approach. We also included a modified version of the SUMSTAT method (mSUMSTAT),
      which tests for association by averaging chi(2) statistics from genotype
      association tests. There were nearly 18000 genes available for analysis,
      following mapping of more than 300,000 SNPs from each data set. These were mapped
      to 421 GO level 4 gene sets for pathway analysis. Among the methods designed to
      be robust to biases related to gene size and pathway SNP correlation (GenGen,
      mSUMSTAT and SLAT), the mSUMSTAT approach identified the most significant
      pathways (8 in CETO and 1 in GRMD). This included a highly plausible association
      for the acetylcholine receptor activity pathway in both CETO (FDR<=0.001) and
      GRMD (FDR = 0.009), although two strong association signals at a single gene
      cluster (CHRNA3-CHRNA5-CHRNB4) drive this result, complicating its
      interpretation. Few other replicated associations were found using any of these
      methods. Difficulty in replicating associations hindered our comparison, but
      results suggest mSUMSTAT has advantages over the other approaches, and may be a
      useful pathway analysis tool to use alongside other methods such as the commonly
      used GSEA (GenGen) approach.

PMID- 22363743
TI  - Identification of CMTM7 as a transmembrane linker of BLNK and the B-cell
      receptor.
AB  - BLNK is a pivotal adaptor protein in the signal transduction pathway from the IgM
      class B-cell receptor. BLNK is phosphorylated by Syk and binds various signaling
      intermediates, leading to cellular events including MAP-kinase activation,
      culminating in cellular activation. It remains unclear how BLNK is initially
      recruited to the surface IgM (sIgM) complex to which Syk is also recruited. Here
      we show that CMTM7, a tetra-spanning membrane protein of unknown function, co
      localized with clathrin and sIgM at the plasma membrane. RNA-interference
      mediated knockdown of CMTM7 expression in B cells resulted in an impairment of
      sIgM-ligation-induced tyrosine phosphorylation of BLNK, which was due to an
      impaired interaction of BLNK and Syk, and in a failure to activate JNK and ERK,
      but not upstream kinases such as Src-family kinases and Syk. CMTM7 was bound to
      BLNK in a membrane fraction, and their association was augmented after sIgM
      ligation. Exogenous CMTM7 or a mutant with an N-terminal deletion (DeltaN), but
      not one with a C-terminal deletion (DeltaC) that is defective in membrane
      localization, were able to restore BLNK-Syk binding, BLNK phosphorylation and ERK
      activation in the CMTM7-knockdown B cells. In addition, CMTM7 and the DeltaN, but
      not the DeltaC, were constitutively associated with sIgM, and this binding was
      required for BLNK recruitment to sIgM. From these data, we conclude that CMTM7
      functions to link sIgM and BLNK in the plasma membrane, to recruit BLNK to the
      vicinity of Syk, and to initiate the BLNK-mediated signal transduction.

PMID- 22363744
TI  - Genes that influence swarming motility and biofilm formation in Variovorax
      paradoxus EPS.
AB  - BACKGROUND: Variovorax paradoxus is an aerobic soil bacterium associated with
      important biodegradative processes in nature. We use V. paradoxus EPS to study
      multicellular behaviors on surfaces. METHODOLOGY: We recovered flanking sequence
      from 123 clones in a Tn5 mutant library, with insertions in 29 different genes,
      selected based on observed surface behavior phenotypes. We identified three
      genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These
      genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We
      also analyzed expression of Varpa_4680 and Varpa_5900 under different growth
      conditions by qPCR. RESULTS: The 29 genes we identified had diverse predicted
      functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly
      recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase
      similar to WbuB. Expression of this gene in trans complemented the mutant fully.
      Several unique insertions were identified in Varpa_5900, which is one of three
      predicted pilY1 homologs in the EPS genome. No insertions in the two other
      putative pilY1 homologs present in the genome were identified. Expression of
      Varpa_5900 altered the structure of the wild type swarm, as did disruption of the
      chromosomal gene. The swarming phenotype was complemented by expression of
      Varpa_5900 from a plasmid, but biofilm formation was not restored. Both
      Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and
      upregulated during swarming when compared to log phase culture. We identified a
      putative two component system (Varpa_4664-4665) encoding a response regulator
      (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation
      increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant.
      Complementation of shkS restored the biofilm phenotype but swarming was still
      delayed. Expression of shkR in trans suppressed biofilm formation in either
      genetic background, and partially restored swarming in the mutant. CONCLUSIONS:
      The data presented here point to complex regulation of these surface behaviors.

PMID- 22363745
TI  - Accumulation of polychlorinated biphenyls in adipocytes: selective targeting to
      lipid droplets and role of caveolin-1.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent environmental
      pollutants that preferentially accumulate in lipid-rich tissues of contaminated
      organisms. Although the adipose tissue constitutes a major intern reservoir of
      PCBs and recent epidemiological studies associate PCBs to the development of
      obesity and its related disorders, little is known about the mechanisms involved
      in their uptake by the adipose tissue and their intracellular localization in fat
      cells. METHODOLOGY/PRINCIPAL FINDINGS: We have examined the intracellular
      distribution of PCBs in mouse cultured adipocytes and tested the potential
      involvement of caveolin-1, an abundant adipocyte membrane protein, in the uptake
      of these compounds by fat cells. We show that 2,4,4'-trichlorobiphenyl (PCB-28),
      2,3',4,4',5-pentachlorobiphenyl (PCB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl
      (PCB-153) congeners rapidly and extensively accumulate in 3T3-L1 or mouse
      embryonic fibroblast (MEF) derived cultured adipocytes. The dynamics of
      accumulation differed between the 3 congeners tested. By subcellular
      fractionation of primary adipocytes, we demonstrate that these pollutants were
      almost exclusively recovered within the lipid droplet fraction and practically
      not associated to cell membranes. The absence of caveolin-1 expression in primary
      adipocytes from cav-1 deficient mice did not modify lipid droplet selective
      targeting of PCBs. In cav-1 KO MEF differentiated adipocytes, PCB accumulation
      was decreased, which correlated with reduced cell triglyceride content.
      Conversely, adenoviral mediated cav-1 overexpressing in 3T3-L1 cells, which had
      no impact on total cell lipid content, did not change PCB accumulation.
      CONCLUSION/SIGNIFICANCE: Our data indicate that caveolin-1 per se is not required
      for selective PCB accumulation, but rather point out a primary dependence on
      adipocyte triglyceride content. If the crucial role of lipid droplets in energy
      homeostasis is considered, the almost exclusive accumulation of PCBs in these
      organelles warrants future attention as the impairment of their function could be
      linked to the worldwide obesity epidemic.

PMID- 22363746
TI  - Drosophila as a model for MECP2 gain of function in neurons.
AB  - Methyl-CpG-binding protein 2 (MECP2) is a multi-functional regulator of gene
      expression. In humans loss of MECP2 function causes classic Rett syndrome, but
      gain of MECP2 function also causes mental retardation. Although mouse models
      provide valuable insight into Mecp2 gain and loss of function, the identification
      of MECP2 genetic targets and interactors remains time intensive and complicated.
      This study takes a step toward utilizing Drosophila as a model to identify
      genetic targets and cellular consequences of MECP2 gain-of function mutations in
      neurons, the principle cell type affected in patients with Rett-related mental
      retardation. We show that heterologous expression of human MECP2 in Drosophila
      motoneurons causes distinct defects in dendritic structure and motor behavior, as
      reported with MECP2 gain of function in humans and mice. Multiple lines of
      evidence suggest that these defects arise from specific MECP2 function. First,
      neurons with MECP2-induced dendrite loss show normal membrane currents. Second,
      dendritic phenotypes require an intact methyl-CpG-binding domain. Third,
      dendritic defects are amended by reducing the dose of the chromatin remodeling
      protein, osa, indicating that MECP2 may act via chromatin remodeling in
      Drosophila. MECP2-induced motoneuron dendritic defects cause specific motor
      behavior defects that are easy to score in genetic screening. In sum, our data
      show that some aspects of MECP2 function can be studied in the Drosophila model,
      thus expanding the repertoire of genetic reagents that can be used to unravel
      specific neural functions of MECP2. However, additional genes and signaling
      pathways identified through such approaches in Drosophila will require careful
      validation in the mouse model.

PMID- 22363747
TI  - Multifunctional adaptive NS1 mutations are selected upon human influenza virus
      evolution in the mouse.
AB  - The role of the NS1 protein in modulating influenza A virulence and host range
      was assessed by adapting A/Hong Kong/1/1968 (H3N2) (HK-wt) to increased virulence
      in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed
      11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt
      virus and reverse genetics to incorporate mutant NS gene segments, we
      demonstrated that all NS1 mutations were adaptive and enhanced virus replication
      (up to 100 fold) in mouse cells and/or lungs. All but one NS1 mutant was
      associated with increased virulence measured by survival and weight loss in the
      mouse. Ten of twelve NS1 mutants significantly enhanced IFN-beta antagonism to
      reduce the level of IFN beta production relative to HK-wt in infected mouse lungs
      at 1 day post infection, where 9 mutants induced viral yields in the lung that
      were equivalent to or significantly greater than HK-wt (up to 16 fold increase).
      Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa
      cleavage and polyadenylation specificity factor (CPSF30) thus demonstrating a
      lack of correlation with reduced IFN beta production. Mutant NS1 genes resulted
      in increased viral mRNA transcription (10 of 12 mutants), and protein production
      (6 of 12 mutants) in mouse cells. Increased transcription activity was
      demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although
      we have shown gain-of-function properties for all mutant NS genes, the
      contribution of the NEP mutations to phenotypic changes remains to be assessed.
      This study demonstrates that NS1 is a multifunctional virulence factor subject to
      adaptive evolution.

PMID- 22363749
TI  - The orthologue of Sjogren's syndrome nuclear autoantigen 1 (SSNA1) in Trypanosoma
      brucei is an immunogenic self-assembling molecule.
AB  - Primary Sjogren's Syndrome (PSS) is a highly prevalent autoimmune disease,
      typically manifesting as lymphocytic infiltration of the exocrine glands leading
      to chronically impaired lacrimal and salivary secretion. Sjogren's Syndrome
      nuclear autoantigen 1 (SSNA1 or NA14) is a major specific target for
      autoantibodies in PSS but the precise function and clinical relevance of this
      protein are largely unknown. Orthologues of the gene are absent from many of the
      commonly used model organisms but are present in Chlamyodomonas reinhardtii (in
      which it has been termed DIP13) and most protozoa. We report the functional
      characterisation of the orthologue of SSNA1 in the kinetoplastid parasite,
      Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins
      which are predicted to be remote homologues of the actin-binding protein
      tropomyosin. We use comparative proteomic methods to identify potential
      interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to
      self-assemble into fibril-like structures both in vitro and in vivo, a property
      which may contribute to its immunogenicity. Endogenous TbDIP13 partially co
      localises with acetylated alpha-tubulin in the insect procyclic stage of the
      parasite. However, deletion of the DIP13 gene in cultured bloodstream and
      procyclic stages of T. brucei has little effect on parasite growth or morphology,
      indicating either a degree of functional redundancy or a function in an
      alternative stage of the parasite life cycle.

PMID- 22363748
TI  - Evolution in Australasian mangrove forests: multilocus phylogenetic analysis of
      the Gerygone warblers (Aves: Acanthizidae).
AB  - The mangrove forests of Australasia have many endemic bird species but their
      evolution and radiation in those habitats has been little studied. One genus with
      several mangrove specialist species is Gerygone (Passeriformes: Acanthizidae).
      The phylogeny of the Acanthizidae is reasonably well understood but limited taxon
      sampling for Gerygone has constrained understanding of its evolution and
      historical biogeography in mangroves. Here we report on a phylogenetic analysis
      of Gerygone based on comprehensive taxon sampling and a multilocus dataset of
      thirteen loci spread across the avian genome (eleven nuclear and two
      mitochondrial loci). Since Gerygone includes three species restricted to
      Australia's coastal mangrove forests, we particularly sought to understand the
      biogeography of their evolution in that ecosystem. Analyses of individual loci,
      as well as of a concatenated dataset drawn from previous molecular studies
      indicates that the genus as currently defined is not monophyletic, and that the
      Grey Gerygone (G. cinerea) from New Guinea should be transferred to the genus
      Acanthiza. The multilocus approach has permitted the nuanced view of the group's
      evolution into mangrove ecosystems having occurred on multiple occasions, in
      three non-overlapping time frames, most likely first by the G. magnirostris
      lineage, and subsequently followed by those of G. tenebrosa and G. levigaster.

PMID- 22363750
TI  - Avian influenza (H5N1) virus of clade 2.3.2 in domestic poultry in India.
AB  - South Asia has experienced regular outbreaks of H5N1 avian influenza virus since
      its first detection in India and Pakistan in February, 2006. Till 2009, the
      outbreaks in this region were due to clade 2.2 H5N1 virus. In 2010, Nepal
      reported the first outbreak of clade 2.3.2 virus in South Asia. In February 2011,
      two outbreaks of H5N1 virus were reported in the State of Tripura in India. The
      antigenic and genetic analyses of seven H5N1 viruses isolated during these
      outbreaks were carried out. Antigenic analysis confirmed 64 to 256-fold reduction
      in cross reactivity compared with clade 2.2 viruses. The intravenous
      pathogenicity index of the isolates ranged from 2.80-2.95 indicating high
      pathogenicity to chickens. Sequencing of all the eight gene-segments of seven
      H5N1 viruses isolated in these outbreaks was carried out. The predicted amino
      acid sequence analysis revealed high pathogenicity to chickens and susceptibility
      to the antivirals, amantadine and oseltamivir. Phylogenetic analyses indicated
      that these viruses belong to clade 2.3.2.1 and were distinct to the clade 2.3.2.1
      viruses isolated in Nepal. Identification of new clade 2.3.2 H5N1 viruses in
      South Asia is reminiscent of the introduction of clade 2.2 viruses in this region
      in 2006/7. It is now important to monitor whether the clade 2.3.2.1 is replacing
      clade 2.2 in this region or co-circulating with it. Continued co-circulation of
      various subclades of the H5N1 virus which are more adapted to land based poultry
      in a highly populated region such as South Asia increases the risk of evolution
      of pandemic H5N1 strains.

PMID- 22363751
TI  - A new single-step PCR assay for the detection of the zoonotic malaria parasite
      Plasmodium knowlesi.
AB  - BACKGROUND: Recent studies in Southeast Asia have demonstrated substantial
      zoonotic transmission of Plasmodium knowlesi to humans. Microscopically, P.
      knowlesi exhibits several stage-dependent morphological similarities to P.
      malariae and P. falciparum. These similarities often lead to misdiagnosis of P.
      knowlesi as either P. malariae or P. falciparum and PCR-based molecular
      diagnostic tests are required to accurately detect P. knowlesi in humans. The
      most commonly used PCR test has been found to give false positive results,
      especially with a proportion of P. vivax isolates. To address the need for more
      sensitive and specific diagnostic tests for the accurate diagnosis of P.
      knowlesi, we report development of a new single-step PCR assay that uses novel
      genomic targets to accurately detect this infection. METHODOLOGY AND SIGNIFICANT
      FINDINGS: We have developed a bioinformatics approach to search the available
      malaria parasite genome database for the identification of suitable DNA sequences
      relevant for molecular diagnostic tests. Using this approach, we have identified
      multi-copy DNA sequences distributed in the P. knowlesi genome. We designed and
      tested several novel primers specific to new target sequences in a single-tube,
      non-nested PCR assay and identified one set of primers that accurately detects P.
      knowlesi. We show that this primer set has 100% specificity for the detection of
      P. knowlesi using three different strains (Nuri, H, and Hackeri), and one human
      case of malaria caused by P. knowlesi. This test did not show cross reactivity
      with any of the four human malaria parasite species including 11 different
      strains of P. vivax as well as 5 additional species of simian malaria parasites.
      CONCLUSIONS: The new PCR assay based on novel P. knowlesi genomic sequence
      targets was able to accurately detect P. knowlesi. Additional laboratory and
      field-based testing of this assay will be necessary to further validate its
      utility for clinical diagnosis of P. knowlesi.

PMID- 22363752
TI  - iPLA2beta overexpression in smooth muscle exacerbates angiotensin II-induced
      hypertension and vascular remodeling.
AB  - OBJECTIVES: Calcium independent group VIA phospholipase A(2) (iPLA(2)beta) is up
      regulated in vascular smooth muscle cells in some diseases, but whether the up
      regulated iPLA(2)beta affects vascular morphology and blood pressure is unknown.
      The current study addresses this question by evaluating the basal- and
      angiotensin II infusion-induced vascular remodeling and hypertension in smooth
      muscle specific iPLA(2)beta transgenic (iPLA(2)beta-Tg) mice. METHOD AND RESULTS:
      Blood pressure was monitored by radiotelemetry and vascular remodeling was
      assessed by morphologic analysis. We found that the angiotensin II-induced
      increase in diastolic pressure was significantly higher in iPLA(2)beta-Tg than
      iPLA(2)beta-Wt mice, whereas, the basal blood pressure was not significantly
      different. The media thickness and media?lumen ratio of the mesenteric arteries
      were significantly increased in angiotensin II-infused iPLA(2)beta-Tg mice.
      Analysis revealed no difference in vascular smooth muscle cell proliferation. In
      contrast, adenovirus-mediated iPLA(2)beta overexpression in cultured vascular
      smooth muscle cells promoted angiotensin II-induced [(3)H]-leucine incorporation,
      indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun
      phosphorylation in vascular smooth muscle cells overexpressing iPLA2beta to
      higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In
      addition, we found that angiotensin II up-regulated the endogenous iPLA(2)beta
      protein in-vitro and in-vivo. CONCLUSION: The present study reports that
      iPLA(2)beta up-regulation exacerbates angiotensin II-induced vascular smooth
      muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15
      lipoxygenase and c-Jun pathways.

PMID- 22363753
TI  - Low-resolution molecular models reveal the oligomeric state of the PPAR and the
      conformational organization of its domains in solution.
AB  - The peroxisome proliferator-activated receptors (PPARs) regulate genes involved
      in lipid and carbohydrate metabolism, and are targets of drugs approved for human
      use. Whereas the crystallographic structure of the complex of full length
      PPARgamma and RXRalpha is known, structural alterations induced by heterodimer
      formation and DNA contacts are not well understood. Herein, we report a small
      angle X-ray scattering analysis of the oligomeric state of hPPARgamma alone and
      in the presence of retinoid X receptor (RXR). The results reveal that, in
      contrast with other studied nuclear receptors, which predominantly form dimers in
      solution, hPPARgamma remains in the monomeric form by itself but forms
      heterodimers with hRXRalpha. The low-resolution models of hPPARgamma/RXRalpha
      complexes predict significant changes in opening angle between heterodimerization
      partners (LBD) and extended and asymmetric shape of the dimer (LBD-DBD) as
      compared with X-ray structure of the full-length receptor bound to DNA. These
      differences between our SAXS models and the high-resolution crystallographic
      structure might suggest that there are different conformations of functional
      heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange
      experiments reveal that the heterodimer binding to DNA promotes more compact and
      less solvent-accessible conformation of the receptor complex.

PMID- 22363755
TI  - Recent HIV-1 infection: identification of individuals with high viral load
      setpoint in a voluntary counselling and testing centre in rural Mozambique.
AB  - BACKGROUND: Identification of recent HIV-infections is important for describing
      the HIV epidemic and compiling HIV-RNA-setpoint data for future HIV intervention
      trials. We conducted a study to characterize recent infections, and HIV-RNA
      setpoint within the adult population presenting at a voluntary counselling and
      testing centre (VCT) in southern Mozambique. METHODS: All adults attending the
      Manhica District-Hospital VCT between April and October 2009 were recruited if
      they had at least one positive rapid HIV-serology test. Patients were screened
      for recent HIV-1 infection by BED-CEIA HIV-incidence test. Clinical examination,
      assessment of HIV-RNA and CD4 cell counts were performed at enrollment, 4 and 10
      months. RESULTS: Of the 492 participants included in this study, the prevalence
      of recent infections as defined by BED-CEIA test, CD4 counts >200 cells/ul and
      HIV-RNA >400 copies/mL, was 11.58% (57/492; 95% CI 8.89-14.74). Due to
      heterogeneity in HIV-RNA levels in recently infected patients, individuals were
      categorized as having "high" HIV-RNA load if their HIV-RNA level was above the
      median (4.98 log(10) copies/mL) at diagnosis. The "high" HIV-RNA group sustained
      a significantly higher HIV-viral load at all visits with a median HIV-RNA
      setpoint of 5.22 log(10) copies/mL (IQR 5.18-5.47) as compared to the median of
      4.15 log(10) copies/ml (IQR 3.37-4.43) for the other patients (p = 0.0001).
      CONCLUSION: The low proportion of recent HIV-infections among HIV-seropositive
      VCT clients suggests that most of this population attends the VCT at later stages
      of HIV/AIDS. Characterization of HIV-RNA-setpoint may serve to identify recently
      infected individuals maintaining HIV viral load>5 log10 copies/mL as candidates
      for antiretroviral treatment as prevention interventions.

PMID- 22363754
TI  - The clathrin assembly protein PICALM is required for erythroid maturation and
      transferrin internalization in mice.
AB  - Phosphatidylinositol binding clathrin assembly protein (PICALM), also known as
      clathrin assembly lymphoid myeloid leukemia protein (CALM), was originally
      isolated as part of the fusion gene CALM/AF10, which results from the chromosomal
      translocation t(10;11)(p13;q14). CALM is sufficient to drive clathrin assembly in
      vitro on lipid monolayers and regulates clathrin-coated budding and the size and
      shape of the vesicles at the plasma membrane. However, the physiological role of
      CALM has yet to be elucidated. Here, the role of CALM in vivo was investigated
      using CALM-deficient mice. CALM-deficient mice exhibited retarded growth in utero
      and were dwarfed throughout their shortened life-spans. Moreover, CALM-deficient
      mice suffered from severe anemia, and the maturation and iron content in
      erythroid precursors were severely impaired. CALM-deficient erythroid cells and
      embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of
      transferrin. These results indicate that CALM is required for erythroid
      maturation and transferrin internalization in mice.

PMID- 22363756
TI  - Mitochondrial function in Antarctic nototheniids with ND6 translocation.
AB  - Fish of the suborder Notothenioidei have successfully radiated into the Southern
      Ocean and today comprise the dominant fish sub-order in Antarctic waters in terms
      of biomass and species abundance. During evolution in the cold and stable
      Antarctic climate, the Antarctic lineage of notothenioids developed several
      unique physiological adaptations, which make them extremely vulnerable to the
      rapid warming of Antarctic waters currently observed. Only recently, a further
      phenomenon exclusive to notothenioid fish was reported: the translocation of the
      mitochondrial gene encoding the NADH Dehydrogenase subunit 6 (ND6), an
      indispensable part of complex I in the mitochondrial electron transport
      system.This study investigated the potential physiological consequences of ND6
      translocation for the function and thermal sensitivity of the electron transport
      system in isolated liver mitochondria of the two nototheniid species Notothenia
      coriiceps and Notothenia rossii, with special attention to the contributions of
      complex I (NADH DH) and complex II (Succinate DH) to oxidative phosphorylation.
      Furthermore, enzymatic activities of NADH:Cytochrome c Oxidoreductase and
      Cytochrome C Oxidase were measured in membrane-enriched tissue extracts.During
      acute thermal challenge (0-15 degrees C), capacities of mitochondrial respiration
      and enzymatic function in the liver could only be increased until 9 degrees C.
      Mitochondrial complex I (NADH Dehydrogenase) was fully functional but displayed a
      higher thermal sensitivity than the other complexes of the electron transport
      system, which may specifically result from its unique amino acid composition,
      revealing a lower degree of stability in notothenioids in general. We interpret
      the translocation of ND6 as functionally neutral but the change in amino acid
      sequence as adaptive and supportive of cold stenothermy in Antarctic
      nototheniids. From these findings, an enhanced sensitivity to ocean warming can
      be deduced for Antarctic notothenioid fish.

PMID- 22363757
TI  - The potential role of ORM2 in the development of colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common malignancy in the world. The
      risk of death is closely correlated to the stage of CRC at the time of primary
      diagnosis. Therefore, there is a compelling need for the identification of blood
      biomarkers that can enable early detection of CRC. We used a quantitative
      proteomic approach with isobaric labeling (iTRAQ) to examine changes in the
      plasma proteome of 10 patients with CRC compared to healthy volunteers. Enzyme
      Linked Immunosorbnent Assay (ELISA) and Western blot were used for further
      validation. In our quantitative proteomics analysis, we detected 75 human plasma
      proteins with more than 95% confidence using iTRAQ labeling in conjunction with
      microQ-TOF MS. 9 up-regulated and 4 down-regulated proteins were observed in the
      CRC group. The ORM2 level in plasma was confirmed to be significantly elevated in
      patients suffering from CRC compared with the controls. ORM2 expression in CRC
      tissues was significantly increased compared with that in corresponding adjacent
      normal mucous tissues (P<0.001). ITRAQ together with Q-TOF/MS is a sensitive and
      reproducible technique of quantitative proteomics. Alteration in expression of
      ORM2 suggests that ORM2 could be used as a potential biomarker in the diagnosis
      of CRC.

PMID- 22363758
TI  - Two cellular protein kinases, DNA-PK and PKA, phosphorylate the adenoviral L4-33K
      protein and have opposite effects on L1 alternative RNA splicing.
AB  - Accumulation of the complex set of alternatively processed mRNA from the
      adenovirus major late transcription unit (MLTU) is subjected to a temporal
      regulation involving both changes in poly (A) site choice and alternative 3'
      splice site usage. We have previously shown that the adenovirus L4-33K protein
      functions as an alternative splicing factor involved in activating the shift from
      L1-52,55K to L1-IIIa mRNA. Here we show that L4-33K specifically associates with
      the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) in uninfected
      and adenovirus-infected nuclear extracts. Further, we show that L4-33K is highly
      phosphorylated by DNA-PK in vitro in a double stranded DNA-independent manner.
      Importantly, DNA-PK deficient cells show an enhanced production of the L1-IIIa
      mRNA suggesting an inhibitory role of DNA-PK on the temporal switch in L1
      alternative RNA splicing. Moreover, we show that L4-33K also is phosphorylated by
      protein kinase A (PKA), and that PKA has an enhancer effect on L4-33K-stimulated
      L1-IIIa splicing. Hence, we demonstrate that these kinases have opposite effects
      on L4-33K function; DNA-PK as an inhibitor and PKA as an activator of L1-IIIa
      mRNA splicing. Taken together, this is the first report identifying protein
      kinases that phosphorylate L4-33K and to suggest novel regulatory roles for DNA
      PK and PKA in adenovirus alternative RNA splicing.

PMID- 22363759
TI  - Wnt signalling pathway parameters for mammalian cells.
AB  - Wnt/beta-catenin signalling regulates cell fate, survival, proliferation and
      differentiation at many stages of mammalian development and pathology. Mutations
      of two key proteins in the pathway, APC and beta-catenin, have been implicated in
      a range of cancers, including colorectal cancer. Activation of Wnt signalling has
      been associated with the stabilization and nuclear accumulation of beta-catenin
      and consequential up-regulation of beta-catenin/TCF gene transcription. In 2003,
      Lee et al. constructed a computational model of Wnt signalling supported by
      experimental data from analysis of time-dependent concentration of Wnt signalling
      proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus
      quantitative data to infer Wnt pathway dynamics in other systems. As a basis for
      understanding Wnt signalling in mammalian cells, a confocal live cell imaging
      measurement technique is developed to measure the cell and nuclear volumes of
      MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the
      concentrations of Wnt signalling proteins beta-catenin, Axin, APC, GSK3beta and E
      cadherin. These parameters provide the basis for formulating Wnt signalling
      models for kidney/intestinal epithelial mammalian cells. There are significant
      differences in concentrations of key proteins between Xenopus extracts and
      mammalian whole cell lysates. Higher concentrations of Axin and lower
      concentrations of APC are present in mammalian cells. Axin concentrations are
      greater than APC in kidney epithelial cells, whereas in intestinal epithelial
      cells the APC concentration is higher than Axin. Computational simulations based
      on Lee's model, with this new data, suggest a need for a recalibration of the
      model.A quantitative understanding of Wnt signalling in mammalian cells, in
      particular human colorectal cancers requires a detailed understanding of the
      concentrations of key protein complexes over time. Simulations of Wnt signalling
      in mammalian cells can be initiated with the parameters measured in this report.

PMID- 22363760
TI  - Loss of secreted frizzled-related protein 4 correlates with an aggressive
      phenotype and predicts poor outcome in ovarian cancer patients.
AB  - BACKGROUND: Activation of the Wnt signaling pathway is implicated in aberrant
      cellular proliferation in various cancers. In 40% of endometrioid ovarian
      cancers, constitutive activation of the pathway is due to oncogenic mutations in
      beta-catenin or other inactivating mutations in key negative regulators. Secreted
      frizzled-related protein 4 (SFRP4) has been proposed to have inhibitory activity
      through binding and sequestering Wnt ligands. METHODOLOGY/PRINCIPAL FINDINGS: We
      performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines
      for SFRP4 and its key downstream regulators activated beta-catenin, beta-catenin
      and GSK3beta. SFRP4 was then examined by immunohistochemistry in a cohort of 721
      patients and due to its proposed secretory function, in plasma, presenting the
      first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and
      decreased with malignant transformation, both on RNA and on protein level, where
      it was even more profound in the membrane fraction (p<0.0001). SFRP4 was
      expressed on the protein level in all histotypes of ovarian cancer but was
      decreased from borderline tumors to cancers and with loss of cellular
      differentiation. Loss of membrane expression was an independent predictor of poor
      survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted),
      which increased the risk of a patient to die from this disease by the factor 1.8.
      CONCLUSIONS/SIGNIFICANCE: Our results support a role for SFRP4 as a tumor
      suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway.
      This has not only predictive implications but could also facilitate a therapeutic
      role using epigenetic targets.

PMID- 22363761
TI  - A cross-sectional study of barriers to personal health record use among patients
      attending a safety-net clinic.
AB  - BACKGROUND: Personal health records (PHR) may improve patients' health by
      providing access to and context for health information. Among patients receiving
      care at a safety-net HIV/AIDS clinic, we examined the hypothesis that a mental
      health (MH) or substance use (SU) condition represents a barrier to engagement
      with web-based health information, as measured by consent to participate in a
      trial that provided access to personal (PHR) or general (non-PHR) health
      information portals and by completion of baseline study surveys posted there.
      METHODS: Participants were individually trained to access and navigate
      individualized online accounts and to complete study surveys. In response to
      need, during accrual months 4 to 12 we enhanced participant training to encourage
      survey completion with the help of staff. Using logistic regression models, we
      estimated odds ratios for study participation and for survey completion by
      combined MH/SU status, adjusted for levels of computer competency, on-study
      training, and demographics. RESULTS: Among 2,871 clinic patients, 70% had MH/SU
      conditions, with depression (38%) and methamphetamine use (17%) most commonly
      documented. Middle-aged patients and those with a MH/SU condition were over
      represented among study participants (N = 338). Survey completion was
      statistically independent of MH/SU status (OR, 1.85 [95% CI, 0.93-3.66]) but
      tended to be higher among those with MH/SU conditions. Completion rates were low
      among beginner computer users, regardless of training level (<50%), but adequate
      among advanced users (>70%). CONCLUSIONS: Among patients attending a safety-net
      clinic, MH/SU conditions were not barriers to engagement with web-based health
      information. Instead, level of computer competency was useful for identifying
      individuals requiring substantial computer training in order to fully participate
      in the study. Intensive on-study training was insufficient to enable beginner
      computer users to complete study surveys.

PMID- 22363762
TI  - The prevalence and cost of unapproved uses of top-selling orphan drugs.
AB  - INTRODUCTION: The Orphan Drug Act encourages drug development for rare
      conditions. However, some orphan drugs become top sellers for unclear reasons. We
      sought to evaluate the extent and cost of approved and unapproved uses of orphan
      drugs with the highest unit sales. METHODS: We assessed prescription patterns for
      four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post
      herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet
      (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib
      (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal
      tumor. We pooled patient-specific diagnosis and prescription data from two large
      US state pharmaceutical benefit programs for the elderly. We analyzed the number
      of new and total patients using each drug and patterns of reimbursement for
      approved and unapproved uses. For lidocaine patch, we subcategorized approved
      prescriptions into two subtypes of unapproved uses: neuropathic pain, for which
      some evidence of efficacy exists, and non-neuropathic pain. RESULTS: We found
      that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with
      non-orphan diagnoses rose at substantially higher rates (average monthly
      increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions
      associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively
      (p<0.001 for all)). By contrast, for imatinib, approved uses increased
      significantly over off-label (0.97 vs. 0.47 patients, p<0.001). Spending on off
      label uses was highest for lidocaine patch and modafinil (>75%). Increases in
      lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2
      vs. 3.6 patients, p<0.001). DISCUSSION: In our sample, three of four top-selling
      orphan drugs were used more commonly for non-orphan indications. These orphan
      drugs treated common clinical symptoms (pain and fatigue) or laboratory
      abnormalities. We should continue to monitor orphan drug use after approval to
      identify products that come to be widely used for non-FDA approved indications,
      particularly those without adequate evidence of efficacy.

PMID- 22363763
TI  - Species-specific effects of epigeic earthworms on microbial community structure
      during first stages of decomposition of organic matter.
AB  - BACKGROUND: Epigeic earthworms are key organisms in organic matter decomposition
      because of the interactions they establish with microorganisms. The earthworm
      species and the quality and/or substrate availability are expected to be major
      factors influencing the outcome of these interactions. Here we tested whether and
      to what extent the epigeic earthworms Eisenia andrei, Eisenia fetida and Perionyx
      excavatus, widely used in vermicomposting, are capable of altering the
      microbiological properties of fresh organic matter in the short-term. We also
      questioned if the earthworm-induced modifications to the microbial communities
      are dependent on the type of substrate ingested. METHODOLOGY/PRINCIPAL FINDINGS:
      To address these questions we determined the microbial community structure
      (phospholipid fatty acid profiles) and microbial activity (basal respiration and
      microbial growth rates) of three types of animal manure (cow, horse and rabbit)
      that differed in microbial composition, after being processed by each species of
      earthworm for one month. No differences were found between earthworm-worked
      samples with regards to microbial community structure, irrespective of type of
      manure, which suggests the existence of a bottleneck effect of worm digestion on
      microbial populations of the original material consumed. Moreover, in mesocosms
      containing cow manure the presence of E. andrei resulted not only in a decrease
      in bacterial and fungal biomass, but also in a reduced bacterial growth rate and
      total microbial activity, while no such reduction was found with E. fetida and P.
      excavatus. CONCLUSIONS/SIGNIFICANCE: Our results point to the species of
      earthworm with its associated gut microbiota as a strong determinant of the
      process shaping the structure of microbial communities in the short-term. This
      must nonetheless be weighed against the fact that further knowledge is necessary
      to evaluate whether the changes in the composition of microbiota in response to
      the earthworm species is accompanied by a change in the microbial community
      diversity and/or function.

PMID- 22363764
TI  - Stable isotope evidence for dietary overlap between alien and native gastropods
      in coastal lakes of northern KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Tarebia granifera (Lamarck, 1822) is originally from South-East Asia,
      but has been introduced and become invasive in many tropical and subtropical
      parts of the world. In South Africa, T. granifera is rapidly invading an
      increasing number of coastal lakes and estuaries, often reaching very high
      population densities and dominating shallow water benthic invertebrate
      assemblages. An assessment of the feeding dynamics of T. granifera has raised
      questions about potential ecological impacts, specifically in terms of its
      dietary overlap with native gastropods. METHODOLOGY/PRINCIPAL FINDINGS: A stable
      isotope mixing model was used together with gut content analysis to estimate the
      diet of T. granifera and native gastropod populations in three different coastal
      lakes. Population density, available biomass of food and salinity were measured
      along transects placed over T. granifera patches. An index of isotopic (stable
      isotopes) dietary overlap (IDO, %) aided in interpreting interactions between
      gastropods. The diet of T. granifera was variable, including contributions from
      microphytobenthos, filamentous algae (Cladophora sp.), detritus and sedimentary
      organic matter. IDO was significant (>60%) between T. granifera and each of the
      following gastropods: Haminoea natalensis (Krauss, 1848), Bulinus natalensis
      (Kuster, 1841) and Melanoides tuberculata (Muller, 1774). However, food did not
      appear to be limiting. Salinity influenced gastropod spatial overlap. Tarebia
      granifera may only displace native gastropods, such as Assiminea cf. ovata
      (Krauss, 1848), under salinity conditions below 20. Ecosystem-level impacts are
      also discussed. CONCLUSION/SIGNIFICANCE: The generalist diet of T. granifera may
      certainly contribute to its successful establishment. However, although
      competition for resources may take place under certain salinity conditions and if
      food is limiting, there appear to be other mechanisms at work, through which T.
      granifera displaces native gastropods. Complementary stable isotope and gut
      content analysis can provide helpful ecological insights, contributing to
      monitoring efforts and guiding further invasive species research.

PMID- 22363765
TI  - Therapeutic trial of metformin and bortezomib in a mouse model of tuberous
      sclerosis complex (TSC).
AB  - Tuberous sclerosis complex (TSC) is a human genetic disorder in which loss of
      either TSC1 or TSC2 leads to development of hamartoma lesions, which can progress
      and be life-threatening or fatal. The TSC1/TSC2 protein complex regulates the
      state of activation of mTORC1. Tsc2(+/-) mice develop renal cystadenoma lesions
      which grow progressively. Both bortezomib and metformin have been proposed as
      potential therapeutics in TSC. We examined the potential benefit of 1 month
      treatment with bortezomib, and 4 month treatment with metformin in Tsc2(+/-)
      mice. Results were compared to vehicle treatment and treatment with the mTORC1
      inhibitor rapamycin for 1 month. We used a quantitative tumor volume measurement
      on stained paraffin sections to assess the effect of these drugs. The median
      tumor volume per kidney was decreased by 99% in mice treated with rapamycin (p =
      0.0004). In contrast, the median tumor volume per kidney was not significantly
      reduced for either the bortezomib cohort or the metformin cohort. Biochemical
      studies confirmed that bortezomib and metformin had their expected
      pharmacodynamic effects. We conclude that neither bortezomib nor metformin has
      significant benefit in this native Tsc2(+/-) mouse model, which suggests limited
      benefit of these compounds in the treatment of TSC hamartomas and related
      lesions.

PMID- 22363767
TI  - Maturational and aging effects on human brain apparent transverse relaxation.
AB  - The goal of this study was to address the need for comprehensive reference data
      regarding maturational and aging effects on regional transverse relaxation rates
      (R(2)) of the brain in normal humans. Regional R(2)s were measured in twenty-five
      brain structures from a sample of seventy-seven normal volunteers 9 to 85 years
      of age. The relationships between regional R(2) and age were determined using
      generalized additive models, without the constraint of a specified a priori
      model. Data analysis demonstrated that the brain tissue R(2)-age correlations
      followed various time courses with both linear and non-linear characteristics
      depending on the particular brain structure. Most anatomical structures studied
      exhibited non-linear characteristics, including the amygdala, hippocampus,
      thalamus, globus pallidus, putamen, caudate nucleus, red nucleus, substantia
      nigra, orbitofrontal white matter and temporal white matter. Linear trends were
      detected in occipital white matter and in the genu of corpus callosum. These
      results indicate the complexity of age-related R(2) changes in the brain while
      providing normative reference data that can be utilized in clinical examinations
      and studies utilizing quantitative transverse relaxation.

PMID- 22363766
TI  - A novel classification of lung cancer into molecular subtypes.
AB  - The remarkably heterogeneous nature of lung cancer has become more apparent over
      the last decade. In general, advanced lung cancer is an aggressive malignancy
      with a poor prognosis. The discovery of multiple molecular mechanisms underlying
      the development, progression, and prognosis of lung cancer, however, has created
      new opportunities for targeted therapy and improved outcome. In this paper, we
      define "molecular subtypes" of lung cancer based on specific actionable genetic
      aberrations. Each subtype is associated with molecular tests that define the
      subtype and drugs that may potentially treat it. We hope this paper will be a
      useful guide to clinicians and researchers alike by assisting in therapy decision
      making and acting as a platform for further study. In this new era of cancer
      treatment, the 'one-size-fits-all' paradigm is being forcibly pushed aside
      allowing for more effective, personalized oncologic care to emerge.

PMID- 22363768
TI  - Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA
      hIL12 fusion protein against Mycobacterium tuberculosis in mice.
AB  - Tuberculosis (TB) remains a major worldwide health problem. The only vaccine
      against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG), has demonstrated
      relatively low efficacy and does not provide satisfactory protection against the
      disease. More efficient vaccines and improved therapies are urgently needed to
      decrease the worldwide spread and burden of TB, and use of a viable, metabolizing
      mycobacteria vaccine may be a promising strategy against the disease. Here, we
      constructed a recombinant Mycobacterium smegmatis (rMS) strain expressing a
      fusion protein of heparin-binding hemagglutinin (HBHA) and human interleukin 12
      (hIL-12). Immune responses induced by the rMS in mice and protection against
      Mycobacterium tuberculosis (MTB) were investigated. Administration of this novel
      rMS enhanced Th1-type cellular responses (IFN-gamma and IL-2) in mice and reduced
      bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile,
      the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine
      also was significantly reduced. In conclusion, the rMS strain expressing the HBHA
      and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type
      response against TB, and the protective effect was equivalent to that of the
      conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load
      and alleviate histopathological damage in lungs of M. tuberculosis infected mice.

PMID- 22363769
TI  - Presence of antibodies against Coxiella burnetii and risk of spontaneous
      abortion: a nested case-control study.
AB  - BACKGROUND AND AIMS: Q fever is a bacterial zoonosis caused by infection with
      Coxiella burnetii. It is well established that Q fever causes fetal loss in small
      ruminants. The suspicion has been raised that pregnant women may also experience
      adverse pregnancy outcome when the infection is acquired or reactivated during
      pregnancy. The purpose of this study was to assess the potential association
      between serologic markers of infection with C. burnetii and spontaneous abortion.
      METHODS: A nested case-control study within the Danish National Birth Cohort, a
      cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in
      first trimester of pregnancy and followed prospectively. Median gestational age
      at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During
      pregnancy, a blood sample was collected at gestational week 6-12 and stored in a
      bio bank. For this study, a case sample of 218 pregnancies was drawn randomly
      among the pregnancies in the cohort which ended with a miscarriage before 22
      gestational weeks, and a reference group of 482 pregnancies was selected in a
      random fashion among all pregnancies in the cohort. From these pregnancies, serum
      samples were screened for antibodies against C. burnetii in a commercial enzyme
      linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody
      positive were subsequently confirmatory tested by an immunofluorescence (IFA)
      test. RESULTS: Among cases, 11 (5%) were C. burnetii positive in ELISA of which
      one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA
      confirmed in the random sample. CONCLUSIONS: We found no evidence of a higher
      prevalence of C. burnetii antibodies in serum samples from women who later
      miscarried and the present study does not indicate a major association between Q
      fever infection and spontaneous abortion in humans. Very early first trimester
      abortions were, however, not included in the study.

PMID- 22363770
TI  - Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study
      in pig.
AB  - Transdermal drug delivery has made a notable contribution to medical practice,
      but has yet to fully achieve its potential as an alternative to oral delivery and
      hypodermic injections. While transdermal delivery systems would appear to provide
      an attractive solution for local and systemic drug delivery, only a limited
      number of drugs can be delivered through the outer layer of the skin. The most
      difficult to deliver in this way are hydrophilic drugs. The aquatic phylum
      Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the
      most ancient multicellular phyla that possess stinging cells containing
      organelles (cnidocysts), comprising a sophisticated injection system. The
      apparatus is folded within collagenous microcapsules and upon activation injects
      a thin tubule that immediately penetrates the prey and delivers its contents.
      Here we show that this natural microscopic injection system can be adapted for
      systemic transdermal drug delivery once it is isolated from the cells and
      uploaded with the drug. Using a topically applied gel containing isolated natural
      sea anemone injectors and the muscarinic receptor antagonist scopolamine, we
      found that the formulated injectors could penetrate porcine skin and immediately
      deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the
      first time, rapid systemic delivery of scopolamine, with T(max) of 30 minutes and
      C(max) 5 times higher than in controls treated topically with a scopolamine
      containing gel without cnidocysts. The ability of the formulated natural
      injection system to penetrate a barrier as thick as the skin and systemically
      deliver an exogenous compound presents an intriguing and attractive alternative
      for hydrophilic transdermal drug delivery.

PMID- 22363771
TI  - Engineering of papaya mosaic virus (PapMV) nanoparticles through fusion of the
      HA11 peptide to several putative surface-exposed sites.
AB  - Papaya mosaic virus has been shown to be an efficient adjuvant and vaccine
      platform in the design and improvement of innovative flu vaccines. So far, all
      fusions based on the PapMV platform have been located at the C-terminus of the
      PapMV coat protein. Considering that some epitopes might interfere with the self
      assembly of PapMV CP when fused at the C-terminus, we evaluated other possible
      sites of fusion using the influenza HA11 peptide antigen. Two out of the six new
      fusion sites tested led to the production of recombinant proteins capable of self
      assembly into PapMV nanoparticles; the two functional sites are located after
      amino acids 12 and 187. Immunoprecipitation of each of the successful fusions
      demonstrated that the HA11 epitope was located at the surface of the
      nanoparticles. The stability and immunogenicity of the PapMV-HA11 nanoparticles
      were evaluated, and we could show that there is a direct correlation between the
      stability of the nanoparticles at 37 degrees C (mammalian body temperature) and
      the ability of the nanoparticles to trigger an efficient immune response directed
      towards the HA11 epitope. This strong correlation between nanoparticle stability
      and immunogenicity in animals suggests that the stability of any nanoparticle
      harbouring the fusion of a new peptide should be an important criterion in the
      design of a new vaccine.

PMID- 22363772
TI  - High-resolution melting analysis for the rapid detection of fluoroquinolone and
      streptomycin resistance in Mycobacterium tuberculosis.
AB  - BACKGROUND: Molecular methods for the detection of drug-resistant tuberculosis
      are potentially more rapid than conventional culture-based drug susceptibility
      testing, facilitating the commencement of appropriate treatment for patients with
      drug resistant tuberculosis. We aimed to develop and evaluate high-resolution
      melting (HRM) assays for the detection of mutations within gyrA, rpsL, and rrs,
      for the determination of fluoroquinolone and streptomycin resistance in
      Mycobacterium tuberculosis (MTB). METHODOLOGY/PRINCIPAL FINDINGS: A blinded
      series of DNA samples extracted from a total of 92 clinical isolates of MTB were
      analyzed by HRM analysis, and the results were verified using DNA sequencing. The
      sensitivity and specificity of the HRM assays in comparison with drug
      susceptibility testing were 74.1% and 100.0% for the detection of fluoroquinolone
      resistance, and 87.5% and 100.0% for streptomycin resistance. Five isolates with
      low level resistance to ofloxacin had no mutations detected in gyrA, possibly due
      to the action of efflux pumps, or false negativity due to mixed infections. One
      fluoroquinolone-resistant isolate had a mutation in a region of gyrA not
      encompassed by our assay. Six streptomycin-resistant strains had undetectable
      mutations by HRM and DNA sequencing, which may be explained by the fact that not
      all streptomycin-resistant isolates have mutations within rpsL and rrs, and
      suggesting that other targets may be involved. CONCLUSION: The HRM assays
      described here are potentially useful adjunct tests for the efficient
      determination of fluoroquinolone and streptomycin resistance in MTB, and could
      facilitate the timely administration of appropriate treatment for patients
      infected with drug-resistant TB.

PMID- 22363773
TI  - FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is
      antagonised by FKBP12.6.
AB  - Changes in FKBP12.6 binding to cardiac ryanodine receptors (RyR2) are implicated
      in mediating disturbances in Ca(2+)-homeostasis in heart failure but there is
      controversy over the functional effects of FKBP12.6 on RyR2 channel gating. We
      have therefore investigated the effects of FKBP12.6 and another structurally
      similar molecule, FKBP12, which is far more abundant in heart, on the gating of
      single sheep RyR2 channels incorporated into planar phospholipid bilayers and on
      spontaneous waves of Ca(2+)-induced Ca(2+)-release in rat isolated permeabilised
      cardiac cells. We demonstrate that FKBP12 is a high affinity activator of RyR2,
      sensitising the channel to cytosolic Ca(2+), whereas FKBP12.6 has very low
      efficacy, but can antagonise the effects of FKBP12. Mathematical modelling of the
      data shows the importance of the relative concentrations of FKBP12 and FKBP12.6
      in determining RyR2 activity. Consistent with the single-channel results,
      physiological concentrations of FKBP12 (3 uM) increased Ca(2+)-wave frequency and
      decreased the SR Ca(2+)-content in cardiac cells. FKBP12.6, itself, had no effect
      on wave frequency but antagonised the effects of FKBP12.We provide a biophysical
      analysis of the mechanisms by which FK-binding proteins can regulate RyR2 single
      channel gating. Our data indicate that FKBP12, in addition to FKBP12.6, may be
      important in regulating RyR2 function in the heart. In heart failure, it is
      possible that an alteration in the dual regulation of RyR2 by FKBP12 and FKBP12.6
      may occur. This could contribute towards a higher RyR2 open probability, 'leaky'
      RyR2 channels and Ca(2+)-dependent arrhythmias.

PMID- 22363774
TI  - The dispanins: a novel gene family of ancient origin that contains 14 human
      members.
AB  - The Interferon induced transmembrane proteins (IFITM) are a family of
      transmembrane proteins that is known to inhibit cell invasion of viruses such as
      HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger
      family of transmembrane (TM) proteins that we call Dispanins, which refers to a
      common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering
      all major eukaryotic groups, and investigated their evolutionary history using
      Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We
      identified ten human genes that together with the known IFITM genes form the
      Dispanin family. We show that the Dispanins first emerged in eukaryotes in a
      common ancestor of choanoflagellates and metazoa, and that the family later
      expanded in vertebrates where it forms four subfamilies (A-D). Interestingly, we
      also find that the family is found in several different phyla of bacteria and
      propose that it was horizontally transferred to eukaryotes from bacteria in the
      common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic
      sequences have a considerably conserved protein structure. In conclusion, we
      introduce a novel family, the Dispanins, together with a nomenclature based on
      the evolutionary origin.

PMID- 22363775
TI  - Novel, real-time cell analysis for measuring viral cytopathogenesis and the
      efficacy of neutralizing antibodies to the 2009 influenza A (H1N1) virus.
AB  - A novel electronic cell sensor array technology, the real-time cell analysis
      (RTCA) system, was developed to monitor cell events. Unlike the conventional
      methods labeling the target cells with fluorescence, luminescence, or light
      absorption, the RTCA system allows for label-free detection of cell processes
      directly without the incorporation of labels. Here, we used this new format to
      measure the cytopathic effect (CPE) of the 2009 influenza A (H1N1) virus and the
      efficacy of neutralizing antibodies in human sera to this virus. The real-time
      dynamic monitoring of CPE was performed on MDCK cell cultures infected with the
      H1N1 virus, ranging from 5.50*10(2) to 5.50*10(7) copies/mL. The resulting CPE
      kinetic curves were automatically recorded and were both time and viral load
      dependent. The CPE kinetics were also distinguishable between different H1N1
      stains, as the onset of CPE induced by the A/Shanghai/37T/2009 H1N1 virus was
      earlier than that of the A/Shanghai/143T/2009 H1N1 virus. Furthermore, inhibition
      of H1N1 virus-induced CPE in the presence of human specific anti-sera was
      detected and quantified using the RTCA system. Antibody titers determined using
      this new neutralization test correlated well with those obtained independently
      via the standard hemagglutination inhibition test. Taken together, this new CPE
      assay format provided label-free and high-throughput measurement of viral growth
      and the effect of neutralizing antibodies, illustrating its potential in
      influenza vaccine studies.

PMID- 22363776
TI  - Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy
      induced by sustained oral exposure to peanuts in sensitized mice.
AB  - BACKGROUND: Food allergy may affect the gastrointestinal tract and eosinophilia
      is often associated with allergic gastrointestinal disorders. Allergy to peanuts
      is a life-threatening condition and effective and safe treatments still need to
      be developed. The present study aimed to evaluate the effects of sustained oral
      exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We
      also evaluated the effects of desensitization with epicutaneous immunotherapy
      (EPIT) on these processes. METHODS: Mice were sensitized by gavages with whole
      peanut protein extract (PPE) given with cholera toxin. Sensitized mice were
      subsequently exposed to peanuts via a specific regimen and were then analysed for
      eosinophilia in the esophagus and gut. We also assessed mRNA expression in the
      esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT
      were tested when intercalated with sensitization and sustained oral peanut
      exposure. RESULTS: Sustained oral exposure to peanuts in sensitized mice led to
      severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e.
      significantly increased influx of eosinophils into the esophageal mucosa (136
      eosinophils/mm(2)) and reduced villus/crypt ratios (1.6+/-0.15). In the sera,
      specific IgE levels significantly increased as did secretion of Th2 cytokines by
      peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2
      immunological response (IgE response and splenocyte secretion of Th2 cytokines)
      as well as esophageal eosinophilia (50 eosinophils/mm(2), p<0.05), mRNA
      expression of Th2 cytokines in tissue--eotaxin (p<0.05), IL-5 (p<0.05), and IL-13
      (p<0.05)--GATA-3 (p<0.05), and intestinal villus sub-atrophia (2.3+/-0.15). EPIT
      also increased specific IgG2a (p<0.05) and mRNA expression of Foxp3 (p<0.05) in
      the esophageal mucosa. CONCLUSIONS: Gastro-intestinal lesions induced by
      sustained oral exposure in sensitized mice are efficaciously treated by allergen
      specific EPIT.

PMID- 22363777
TI  - A genome-wide study of cytogenetic changes in colorectal cancer using SNP
      microarrays: opportunities for future personalized treatment.
AB  - In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied
      using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor
      and surrounding healthy) fresh frozen tissue from 86 CRC patients using
      Illumina's Infinium-based SNP array. This method allowed us to study CIN in CRC,
      with simultaneous analysis of copy number (CN) and B-allele frequency (BAF)--a
      representation of allelic composition. These data helped us to detect mono
      allelic and bi-allelic amplifications/deletion, copy neutral loss of
      heterozygosity, and levels of mosaicism for mixed cell populations, some of which
      can not be assessed with other methods that do not measure BAF. We identified
      associations between CN abnormalities and different CRC phenotypes (histological
      diagnosis, location, tumor grade, stage, MSI and presence of lymph node
      metastasis). We showed commonalities between regions of CN change observed in CRC
      and the regions reported in previous studies of other solid cancers (e.g.
      amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From
      Therapeutic Target Database, we identified relevant drugs, targeted to the genes
      located in these regions with CN changes, approved or in trials for other cancers
      and common diseases. These drugs may be considered for future therapeutic trials
      in CRC, based on personalized cytogenetic diagnosis. We also found many regions,
      harboring genes, which are not currently targeted by any relevant drugs that may
      be considered for future drug discovery studies. Our study shows the application
      of high density SNP arrays for cytogenetic study in CRC and its potential utility
      for personalized treatment.

PMID- 22363778
TI  - Divergent pro-inflammatory profile of human dendritic cells in response to
      commensal and pathogenic bacteria associated with the airway microbiota.
AB  - Recent studies using culture-independent methods have characterized the human
      airway microbiota and report microbial communities distinct from other body
      sites. Changes in these airway bacterial communities appear to be associated with
      inflammatory lung disease, yet the pro-inflammatory properties of individual
      bacterial species are unknown. In this study, we compared the immune stimulatory
      capacity on human monocyte-derived dendritic cells (DCs) of selected airway
      commensal and pathogenic bacteria predominantly associated with lungs of asthma
      or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs
      (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces
      spp.). All bacteria were found to induce activation of DCs as demonstrated by
      similar induction of CD83, CD40 and CD86 surface expression. However, asthma and
      COPD-associated pathogenic bacteria provoked a 3-5 fold higher production of IL
      23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the
      differential cytokine production profiles, the studied airway bacteria could be
      segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella
      spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory
      effects on DCs. Co-culture experiments found that Prevotella spp. were able to
      reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was
      observed on IL-23 and IL-10 production. This study demonstrates intrinsic
      differences in DC stimulating properties of bacteria associated with the airway
      microbiota.

PMID- 22363779
TI  - ER-alpha-cDNA as part of a bicistronic transcript gives rise to high frequency,
      long term, receptor expressing cell clones.
AB  - Within the large group of Estrogen Receptor alpha (ERalpha)-negative breast
      cancer patients, there is a subgroup carrying the phenotype ERalpha(-), PR(-),
      and Her2(-), named accordingly "Triple-Negative" (TN). Using cell lines derived
      from this TN group, we wished to establish cell clones, in which ERalpha is
      ectopically expressed, forming part of a synthetic lethality screening system.
      Initially, we generated cell transfectants expressing a mono-cistronic ERalpha
      transcription unit, adjacent to a separate dominant selectable marker
      transcription unit. However, the yield of ERalpha expressing colonies was rather
      low (5-12.5%), and only about half of these displayed stable ectopic ERalpha
      expression over time. Generation and maintenance of such cell clones under
      minimal exposure to the ERalpha ligand, did not improve yield or expression
      stability. Indeed, other groups have also reported grave difficulties in
      obtaining ectopic expression of ERalpha in ERalpha-deficient breast carcinoma
      cells. We therefore switched to transfecting these cell lines with pERalpha-IRES,
      a plasmid vector encoding a bicistronic translation mRNA template: ERalpha Open
      Reading Frame (ORF) being upstream followed by a dominant-positive selectable
      marker (hygro(R)) ORF, directed for translation from an Internal Ribosome Entry
      Site (IRES). Through usage of this bicistronic vector linkage system, it was
      possible to generate a very high yield of ERalpha expressing cell clones (50
      100%). The stability over time of these clones was also somewhat improved, though
      variations between individual cell clones were evident. Our successful experience
      with ERalpha in this system may serve as a paradigm for other genes where ectopic
      expression meets similar hardships.

PMID- 22363780
TI  - Mature and precursor brain-derived neurotrophic factor have individual roles in
      the mouse olfactory bulb.
AB  - BACKGROUND: Sensory deprivation induces dramatic morphological and neurochemical
      changes in the olfactory bulb (OB) that are largely restricted to glomerular and
      granule layer interneurons. Mitral cells, pyramidal-like neurons, are resistant
      to sensory-deprivation-induced changes and are associated with the precursor to
      brain-derived neurotrophic factor (proBDNF); here, we investigate its unknown
      function in the adult mouse OB. PRINCIPAL FINDINGS: As determined using brain
      slice electrophysiology in a whole-cell configuration, brain-derived neurotrophic
      factor (BDNF), but not proBDNF, increased mitral cell excitability. BDNF
      increased mitral cell action potential firing frequency and decreased interspike
      interval in response to current injection. In a separate set of experiments,
      intranasal delivery of neurotrophic factors to awake, adult mice was performed to
      induce sustained interneuron neurochemical changes. ProBDNF, but not BDNF,
      increased activated-caspase 3 and reduced tyrosine hydroxylase immunoreactivity
      in OB glomerular interneurons. In a parallel set of experiments, short-term
      sensory deprivation produced by unilateral naris occlusion generated an identical
      phenotype. CONCLUSIONS: Our results indicate that only mature BDNF increases
      mitral cell excitability whereas proBDNF remains ineffective. Our demonstration
      that proBDNF activates an apoptotic marker in vivo is the first for any
      proneurotrophin and establishes a role for proBDNF in a model of neuronal
      plasticity.

PMID- 22363781
TI  - Attenuation of vaccinia Tian Tan strain by removal of viral TC7L-TK2L and TA35R
      genes.
AB  - Vaccinia Tian Tan (VTT) was attenuated by deletion of the TC7L-TK2L and TA35R
      genes to generate MVTT3. The mutant was generated by replacing the open reading
      frames by a gene encoding enhanced green fluorescent protein (EGFP) flanked by
      loxP sites. Viruses expressing EGFP were then screened for and purified by serial
      plaque formation. In a second step the marker EGFP gene was removed by
      transfecting cells with a plasmid encoding cre recombinase and selecting for
      viruses that had lost the EGFP phenotype. The MVTT3 mutant was shown to be
      avirulent and immunogenic. These results support the conclusion that TC7L-TK2L
      and TA35R deletion mutants can be used as safe viral vectors or as platform for
      vaccines.

PMID- 22363782
TI  - Is there a valence-specific pattern in emotional conflict in major depressive
      disorder? An exploratory psychological study.
AB  - OBJECTIVE: Patients with major depressive disorder (MDD) clinically exhibit a
      deficit in positive emotional processing and are often distracted by especially
      negative emotional stimuli. Such emotional-cognitive interference in turn hampers
      the cognitive abilities of patients in their ongoing task. While the
      psychological correlates of such emotional conflict have been well identified in
      healthy subjects, possible alterations of emotional conflict in depressed
      patients remain to be investigated. We conducted an exploratory psychological
      study to investigate emotional conflict in MDD. We also distinguished depression
      related stimuli from negative stimuli in order to check whether the depression
      related distractors will induce enhanced conflict in MDD. METHODS: A typical word
      face Stroop paradigm was adopted. In order to account for valence-specificities
      in MDD, we included positive and general negative as well as depression-related
      words in the study. RESULTS: MDD patients demonstrated a specific pattern of
      emotional conflict clearly distinguishable from the healthy control group. In
      MDD, the positive distractor words did not significantly interrupt the processing
      of the negative target faces, while they did in healthy subjects. On the other
      hand, the depression-related distractor words induced significant emotional
      conflict to the positive target faces in MDD patients but not in the healthy
      control group. CONCLUSION: Our findings demonstrated for the first time an
      altered valence-specific pattern in emotional conflict in MDD patients. The study
      sheds a novel and specific light on the affective mechanisms underlying the
      abnormal emotional-cognitive interference in MDD. Such emotional conflict bears
      important clinical relevance since it may trigger the widespread cognitive
      dysfunctions frequently observed in MDD. The present findings may have important
      clinical implications in both prediction and psychotherapy of MDD.

PMID- 22363783
TI  - Comparison of phenotypes between different vangl2 mutants demonstrates dominant
      effects of the Looptail mutation during hair cell development.
AB  - Experiments utilizing the Looptail mutant mouse, which harbors a missense
      mutation in the vangl2 gene, have been essential for studies of planar polarity
      and linking the function of the core planar cell polarity proteins to other
      developmental signals. Originally described as having dominant phenotypic traits,
      the molecular interactions underlying the Looptail mutant phenotype are unclear
      because Vangl2 protein levels are significantly reduced or absent from mutant
      tissues. Here we introduce a vangl2 knockout mouse and directly compare the
      severity of the knockout and Looptail mutant phenotypes by intercrossing the two
      lines and assaying the planar polarity of inner ear hair cells. Overall the
      vangl2 knockout phenotype is milder than the phenotype of compound mutants
      carrying both the Looptail and vangl2 knockout alleles. In compound mutants a
      greater number of hair cells are affected and changes in the orientation of
      individual hair cells are greater when quantified. We further demonstrate in a
      heterologous cell system that the protein encoded by the Looptail mutation
      (Vangl2(S464N)) disrupts delivery of Vangl1 and Vangl2 proteins to the cell
      surface as a result of oligomer formation between Vangl1 and Vangl2(S464N), or
      Vangl2 and Vangl2(S464N), coupled to the intracellular retention of
      Vangl2(S464N). As a result, Vangl1 protein is missing from the apical cell
      surface of vestibular hair cells in Looptail mutants, but is retained at the
      apical cell surface of hair cells in vangl2 knockouts. Similarly the distribution
      of Prickle-like2, a putative Vangl2 interacting protein, is differentially
      affected in the two mutant lines. In summary, we provide evidence for a direct
      physical interaction between Vangl1 and Vangl2 through a combination of in vitro
      and in vivo approaches and propose that this interaction underlies the dominant
      phenotypic traits associated with the Looptail mutation.

PMID- 22363784
TI  - Challenges in whole exome sequencing: an example from hereditary deafness.
AB  - Whole exome sequencing provides unprecedented opportunities to identify causative
      DNA variants in rare Mendelian disorders. Finding the responsible mutation via
      traditional methods in families with hearing loss is difficult due to a high
      degree of genetic heterogeneity. In this study we combined autozygosity mapping
      and whole exome sequencing in a family with 3 affected children having
      nonsyndromic hearing loss born to consanguineous parents. Two novel missense
      homozygous variants, c.508C>A (p.H170N) in GIPC3 and c.1328C>T (p.T443M) in
      ZNF57, were identified in the same ~6 Mb autozygous region on chromosome 19 in
      affected members of the family. Both variants co-segregated with the phenotype
      and were absent in 335 ethnicity-matched controls. Biallelic GIPC3 mutations have
      recently been reported to cause autosomal recessive nonsyndromic sensorineural
      hearing loss. Thus we conclude that the hearing loss in the family described in
      this report is caused by a novel missense mutation in GIPC3. Identified variant
      in GIPC3 had a low read depth, which was initially filtered out during the
      analysis leaving ZNF57 as the only potential causative gene. This study
      highlights some of the challenges in the analyses of whole exome data in the bid
      to establish the true causative variant in Mendelian disease.

PMID- 22363785
TI  - Two major autoantibody clusters in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a chronic autoimmune disease of complex clinical
      presentation and etiology and is likely influenced by numerous genetic and
      environmental factors. While a large number of susceptibility genes have been
      identified, the production of antibodies against a distinct subset of nuclear
      proteins remains a primary distinguishing characteristic in disease diagnosis.
      However, the utility of autoantibody biomarkers for disease sub-classification
      and grouping remains elusive, in part, because of the difficulty in large scale
      profiling using a uniform, quantitative platform. In the present study
      serological profiles of several known SLE antigens, including Sm-D3, RNP-A, RNP
      70k, Ro52, Ro60, and La, as well as other cytokine and neuronal antigens were
      obtained using the luciferase immunoprecipitation systems (LIPS) approach. The
      resulting autoantibody profiles revealed that 88% of a pilot cohort and 98% of a
      second independent cohort segregated into one of two distinct clusters defined by
      autoantibodies against Sm/anti-RNP or Ro/La autoantigens, proteins often involved
      in RNA binding activities. The Sm/RNP cluster was associated with a higher
      prevalence of serositis in comparison to the Ro/La cluster (P = 0.0022). However,
      from the available clinical information, no other clinical characteristics were
      associated with either cluster. In contrast, evaluation of autoantibodies on an
      individual basis revealed an association between anti-Sm (P = 0.006), RNP-A (P =
      0.018) and RNP-70k (P = 0.010) autoantibodies and mucocutaneous symptoms and
      between anti-RNP-70k and musculoskeletal manifestations (P = 0.059).
      Serologically active, but clinically quiescent disease also had a higher
      prevalence of anti-IFN-alpha autoantibodies. Based on our findings that most SLE
      patients belong to either a Sm/RNP or Ro/La autoantigen cluster, these results
      suggest the possibility that alterations in RNA-RNA-binding protein interactions
      may play a critical role in triggering and/or the pathogenesis of SLE.

PMID- 22363786
TI  - Normal hematopoietic stem cell function in mice with enforced expression of the
      Hippo signaling effector YAP1.
AB  - The Hippo pathway has recently been implicated in the regulation of organ size
      and stem cells in multiple tissues. The transcriptional cofactor yes-associated
      protein 1 (Yap1) is the most downstream effector of Hippo signaling and is
      functionally repressed by the upstream components of the pathway. Overexpression
      of YAP1 stimulates proliferation of stem and progenitor cells in many tissues,
      consistent with inhibition of Hippo signaling. To study the role of Hippo
      signaling in hematopoietic stem cells (HSCs), we created a transgenic model with
      inducible YAP1 expression exclusively within the hematopoietic system. Following
      3 months induction, examination of blood and bone marrow in the induced mice
      revealed no changes in the distribution of the hematopoietic lineages compared to
      control mice. Moreover, the progenitor cell compartment was unaltered as
      determined by colony forming assays and immunophenotyping. To address whether
      YAP1 affects the quantity and function of HSCs we performed competitive
      transplantation experiments. We show that ectopic YAP1 expression does not
      influence HSC function neither during steady state nor in situations of
      hematopoietic stress. This is in sharp contrast to effects seen on stem- and
      progenitor cells in other organs and suggests highly tissue specific functions of
      the Hippo pathway in regulation of stem cells.

PMID- 22363787
TI  - Bmi-1 absence causes premature brain degeneration.
AB  - Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle
      regulation and cell senescence. Its absence results in generalized astrogliosis
      and epilepsy during the postnatal development, but the underlying mechanisms are
      poorly understood. Here, we demonstrate the occurrence of oxidative stress in the
      brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of
      neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis
      and brain mitochondrial damage. Moreover, astroglial glutamate transporters and
      glutamine synthetase decreased in the Bmi-1 null hippocampus, which might
      contribute to the sporadic epileptic-like seizures in these mice. These results
      indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses
      in the brain, and its absence subsequently causes premature brain degeneration.

PMID- 22363788
TI  - Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of
      Parkinson's disease.
AB  - Cells of the neural stem cell lineage in the adult subventricular zone (SVZ)
      respond to brain insult by increasing their numbers and migrating through the
      rostral migratory stream. However, in most areas of the brain other than the SVZ
      and the subgranular zone of the dentate gyrus, such a regenerative response is
      extremely weak. Even these two neurogenic regions do not show extensive
      regenerative responses to repair tissue damage, suggesting the presence of an
      intrinsic inhibitory microenvironment (niche) for stem cells. In the present
      study, we assessed the effects of injection of clustered ephrin-A1-Fc into the
      lateral ventricle of rats with unilateral nigrostriatal dopamine depletion.
      Ephrin-A1-Fc clustered by anti-IgG(Fc) antibody was injected stereotaxically into
      the ipsilateral lateral ventricle of rats with unilateral nigrostriatal lesions
      induced by 6-hydroxydopamine, and histologic analysis and behavioral tests were
      performed. Clustered ephrin-A1-Fc transformed the subventricular niche,
      increasing bromodeoxyuridine-positive cells in the subventricular area, and the
      cells then migrated to the striatum and differentiated to dopaminergic neurons
      and astrocytes. In addition, clustered ephrin-A1-Fc enhanced angiogenesis in the
      striatum on the injected side. Along with histologic improvements, behavioral
      derangement improved dramatically. These findings indicate that the
      subventricular niche possesses a mechanism for regulating both stem cell and
      angiogenic responses via an EphA-mediated signal. We conclude that activation of
      EphA receptor-mediated signaling by clustered ephrin-A1-Fc from within the
      lateral ventricle could potentially be utilized in the treatment of
      neurodegenerative diseases such as Parkinson's disease.

PMID- 22363789
TI  - Presenting the uncertainties of odds ratios using empirical-Bayes prediction
      intervals.
AB  - Quantifying exposure-disease associations is a central issue in epidemiology.
      Researchers of a study often present an odds ratio (or a logarithm of odds ratio,
      logOR) estimate together with its confidence interval (CI), for each exposure
      they examined. Here the authors advocate using the empirical-Bayes-based
      'prediction intervals' (PIs) to bound the uncertainty of logORs. The PI approach
      is applicable to a panel of factors believed to be exchangeable (no extra
      information, other than the data itself, is available to distinguish some logORs
      from the others). The authors demonstrate its use in a genetic epidemiological
      study on age-related macular degeneration (AMD). The proposed PIs can enjoy
      straightforward probabilistic interpretations--a 95% PI has a probability of 0.95
      to encompass the true value, and the expected number of true values that are
      being encompassed is 0.95m for a total of m 95% PIs. The PI approach is
      theoretically more efficient (producing shorter intervals) than the traditional
      CI approach. In the AMD data, the average efficiency gain is 51.2%. The PI
      approach is advocated to present the uncertainties of many logORs in a study, for
      its straightforward probabilistic interpretations and higher efficiency while
      maintaining the nominal coverage probability.

PMID- 22363791
TI  - Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation
      in breast cancer cells.
AB  - BACKGROUND: The sestrin family of stress-responsive genes (SESN1-3) are suggested
      to be involved in regulation of metabolism and aging through modulation of the
      AMPK-mTOR pathway. AMP-activated protein kinase (AMPK) is an effector of the
      tumour suppressor LKB1, which regulates energy homeostasis, cell polarity, and
      the cell cycle. SESN1/2 can interact directly with AMPK in response to stress to
      maintain genomic integrity and suppress tumorigenesis. Ionizing radiation (IR), a
      widely used cancer therapy, is known to increase sestrin expression, and acutely
      activate AMPK. However, the regulation of AMPK expression by sestrins in response
      to IR has not been studied in depth. METHODS AND FINDINGS: Through
      immunoprecipitation we observed that SESN2 directly interacted with the
      AMPKalpha1beta1gamma1 trimer and its upstream regulator LKB1 in MCF7 breast
      cancer cells. SESN2 overexpression was achieved using a Flag-tagged SESN2
      expression vector or a stably-integrated tetracycline-inducible system, which
      also increased AMPKalpha1 and AMPKbeta1 subunit phosphorylation, and co-localized
      with phosphorylated AMPKalpha-Thr127 in the cytoplasm. Furthermore, enhanced
      SESN2 expression increased protein levels of LKB1 and AMPKalpha1beta1gamma1, as
      well as mRNA levels of LKB1, AMPKalpha1, and AMPKbeta1. Treatment of MCF7 cells
      with IR elevated AMPK expression and activity, but this effect was attenuated in
      the presence of SESN2 siRNA. In addition, elevated SESN2 inhibited IR-induced
      mTOR signalling and sensitized MCF7 cells to IR through an AMPK-dependent
      mechanism. CONCLUSIONS: Our results suggest that in breast cancer cells SESN2 is
      associated with AMPK, it is involved in regulation of basal and IR-induced
      expression and activation of this enzyme, and it mediates sensitization of cancer
      cells to IR.

PMID- 22363790
TI  - Circulating sCD14 is associated with virological response to pegylated-interferon
      alpha/ribavirin treatment in HIV/HCV co-infected patients.
AB  - OBJECTIVES: Microbial translocation (MT) through the gut accounts for immune
      activation and CD4+ loss in HIV and may influence HCV disease progression in
      HIV/HCV co-infection. We asked whether increased MT and immune activation may
      hamper anti-HCV response in HIV/HCV patients. METHODS: 98 HIV/HCV patients who
      received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were
      retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to
      MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were
      assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week
      12 of therapy or >=2 log(10) reduction from baseline after 12 weeks of therapy)
      and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of
      therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used.
      Multivariable regression was performed to determine factors associated with
      EVR/SVR. RESULTS: 71 patients displayed EVR; 41 SVR. Patients with HCV genotypes
      1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with
      genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients
      showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively),
      but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non
      SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for
      each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with
      HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p =
      0.014). CONCLUSIONS: In HIV/HCV patients sCD14 correlates with the severity of
      liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting
      MT-driven immune activation as pathway of HIV/HCV co-infection and response to
      therapy.

PMID- 22363792
TI  - Regulation of neuronal APL-1 expression by cholesterol starvation.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by the deposition of beta-amyloid plaques composed primarily of the
      amyloid-beta peptide, a cleavage product of amyloid precursor protein (APP).
      While mutations in APP lead to the development of Familial Alzheimer's Disease
      (FAD), sporadic AD has only one clear genetic modifier: the epsilon4 allele of
      the apolipoprotein E (ApoE) gene. Cholesterol starvation in Caenorhabditis
      elegans leads to molting and arrest phenotypes similar to loss-of-function
      mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1), and lrp-1
      (lipoprotein receptor-related protein 1), suggesting a potential interaction
      between apl-1 and cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS:
      Previously, we found that RNAi knock-down of apl-1 leads to aldicarb
      hypersensitivity, indicating a defect in synaptic function. Here we find the same
      defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A
      cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead
      to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does
      not affect global transcription or protein levels as seen by qPCR and Western
      blot. CONCLUSIONS: Our results show that cholesterol and lrp-1 are involved in
      the regulation of synaptic transmission, similar to apl-1. Both are able to
      modulate APL-1 protein levels in neurons, however cholesterol changes do not
      affect global apl-1 transcription or APL-1 protein indicating the changes are
      specific to neurons. Thus, regulation of synaptic transmission and molting by LRP
      1 and cholesterol may be mediated by their ability to control APL-1 neuronal
      protein expression.

PMID- 22363793
TI  - Toward low-cost affinity reagents: lyophilized yeast-scFv probes specific for
      pathogen antigens.
AB  - The generation of affinity reagents, usually monoclonal antibodies, remains a
      critical bottleneck in biomedical research and diagnostic test development.
      Recombinant antibody-like proteins such as scFv have yet to replace traditional
      monoclonal antibodies in antigen detection applications, in large part because of
      poor performance of scFv in solution. To address this limitation, we have
      developed assays that use whole yeast cells expressing scFv on their surfaces
      (yeast-scFv) in place of soluble purified scFv or traditional monoclonal
      antibodies. In this study, a nonimmune library of human scFv displayed on the
      surfaces of yeast cells was screened for clones that bind to recombinant cyst
      proteins of Entamoeba histolytica, an enteric pathogen of humans. Selected yeast
      scFv clones were stabilized by lyophilization and used in detection assay formats
      in which the yeast-scFv served as solid support-bound monoclonal antibodies.
      Specific binding of antigen to the yeast-scFv was detected by staining with
      rabbit polyclonal antibodies. In flow cytometry-based assays, lyophilized yeast
      scFv reagents retained full binding activity and specificity for their cognate
      antigens after 4 weeks of storage at room temperature in the absence of
      desiccants or stabilizers. Because flow cytometry is not available to all
      potential assay users, an immunofluorescence assay was also developed that
      detects antigen with similar sensitivity and specificity. Antigen-specific whole
      cell yeast-scFv reagents can be selected from nonimmune libraries in 2-3 weeks,
      produced in vast quantities, and packaged in lyophilized form for extended shelf
      life. Lyophilized yeast-scFv show promise as low cost, renewable alternatives to
      monoclonal antibodies for diagnosis and research.

PMID- 22363794
TI  - System-wide immunohistochemical analysis of protein co-localization.
AB  - BACKGROUND: The analysis of co-localized protein expression in a tissue section
      is often conducted with immunofluorescence histochemical staining which is
      typically visualized in localized regions. On the other hand, chromogenic
      immunohistochemical staining, in general, is not suitable for the detection of
      protein co-localization. Here, we developed a new protocol, based on chromogenic
      immunohistochemical stain, for system-wide detection of protein co-localization
      and differential expression. METHODOLOGY/PRINCIPAL FINDINGS: In combination with
      a removable chromogenic stain, an efficient antibody stripping method was
      developed to enable sequential immunostaining with different primary antibodies
      regardless of antibody's host species. Sections were scanned after each staining,
      and the images were superimposed together for the detection of protein co
      localization and differential expression. As a proof of principle, differential
      expression and co-localization of glutamic acid decarboxylase67 (GAD67) and
      parvalbumin proteins was examined in mouse cortex. CONCLUSIONS/SIGNIFICANCE: All
      parvalbumin-containing neurons express GAD67 protein, and GAD67-positive neurons
      that do not express parvalbumin were readily visualized from thousands of other
      neurons across mouse cortex. The method provided a global view of protein co
      localization as well as differential expression across an entire tissue section.
      Repeated use of the same section could combine assessments of co-localization and
      differential expression of multiple proteins.

PMID- 22363795
TI  - DNA barcoding the Dioscorea in China, a vital group in the evolution of
      monocotyledon: use of matK gene for species discrimination.
AB  - BACKGROUND: Dioscorea is an important plant genus in terms of food supply and
      pharmaceutical applications. However, its classification and identification are
      controversial. DNA barcoding is a recent aid to taxonomic identification and uses
      a short standardized DNA region to discriminate plant species. In this study, the
      applicability of three candidate DNA barcodes (rbcL, matK, and psbA-trnH) to
      identify species within Dioscorea was tested. METHODOLOGY/PRINCIPAL FINDINGS: One
      hundred and forty-eight individual plant samples of Dioscorea, encompassing 38
      species, seven varieties and one subspecies, representing majority species
      distributed in China of this genus, were collected from its main distributing
      areas. Samples were assessed by PCR amplification, sequence quality, extent of
      specific genetic divergence, DNA barcoding gap, and the ability to discriminate
      between species. matK successfully identified 23.26% of all species, compared
      with 9.30% for rbcL and 11.63% for psbA-trnH. Therefore, matK is recommended as
      the best DNA barcoding candidate. We found that the combination of two or three
      loci achieved a higher success rate of species discrimination than one locus
      alone. However, experimental cost would be much higher if two or three loci,
      rather than a single locus, were assessed. CONCLUSIONS: We conclude that matK is
      a strong, although not perfect, candidate as a DNA barcode for Dioscorea
      identification. This assessment takes into account both its ability for species
      discrimination and the cost of experiments.

PMID- 22363796
TI  - Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve
      repair after nerve crush in mice, and in human neuropathies.
AB  - Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve
      regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin
      and vitronectin associates with poor regeneration and worse clinical prognosis.
      Accordingly in animal models, modification of the fibrinolytic complex activity
      has profound effects on nerve regeneration: high fibrinolytic activity and low
      levels of fibrin correlate with better nerve regeneration. The urokinase
      plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and
      binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell
      movement. uPAR is expressed in peripheral nerves, however, little is known on its
      potential function on nerve development and regeneration. Thus, we investigated
      uPAR null mice and observed that uPAR is dispensable for nerve development,
      whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced
      nerve repair after sciatic nerve crush. This was a consequence of reduced
      fibrinolytic activity and increased deposition of endoneurial fibrin and
      vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after
      sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural
      nerve biopsies from patients with peripheral neuropathies. We showed that
      neuropathies with defective regeneration had reduced fibrinolytic activity. On
      the contrary, neuropathies with signs of active regeneration displayed higher
      fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis
      may facilitate regeneration and outcome of peripheral neuropathies.

PMID- 22363797
TI  - Roles of salivary components in Streptococcus mutans colonization in a new animal
      model using NOD/SCID.e2f1-/- mice.
AB  - Streptococcus mutans plays an important role in biofilm formation on the tooth
      surface and is the primary causative agent of dental caries. The binding of S.
      mutans to the salivary pellicle is of considerable etiologic significance and is
      important in biofilm development. Recently, we produced NOD/SCID.e2f1(-/-) mice
      that show hyposalivation, lower salivary antibody, and an extended life span
      compared to the parent strain: NOD.e2f1(-/-). In this study we used
      NOD/SCID.e2f1(-/-) 4 or 6 mice to determine the roles of several salivary
      components in S. mutans colonization in vivo. S. mutans colonization in
      NOD/SCID.e2f1(-/-) mice was significantly increased when mice were pre-treated
      with human saliva or commercial salivary components. Interestingly, pre-treatment
      with secretory IgA (sIgA) at physiological concentrations promoted significant
      colonization of S. mutans compared with sIgA at higher concentrations, or with
      human saliva or other components. Our data suggest the principal effects of
      specific sIgA on S. mutans occur during S. mutans colonization, where the
      appropriate concentration of specific sIgA may serve as an anti-microbial agent,
      agglutinin, or an adherence receptor to surface antigens. Further, specific sIgA
      supported biofilm formation when the mice were supplied 1% sucrose water and a
      non-sucrose diet. The data suggests that there are multiple effects exerted by
      sIgA in S. mutans colonization, with synergistic effects evident under the
      condition of sIgA and limited nutrients on colonization in NOD/SCID.e2f1(-/-)
      mice. This is a new animal model that can be used to assess prevention methods
      for dental biofilm-dependent diseases such as dental caries.

PMID- 22363798
TI  - Adjuvant properties of thermal component of hyperthermia enhanced transdermal
      immunization: effect on dendritic cells.
AB  - Hyperthermia enhanced transdermal (HET) immunization is a novel needle free
      immunization strategy employing application of antigen along with mild local
      hyperthermia (42 degrees C) to intact skin resulting in detectable antigen
      specific Ig in serum. In the present study, we investigated the adjuvant effect
      of thermal component of HET immunization in terms of maturation of dendritic
      cells and its implication on the quality of the immune outcome in terms of
      antibody production upon HET immunization with tetanus toxoid (TT). We have shown
      that in vitro hyperthermia exposure at 42 degrees C for 30 minutes up regulates
      the surface expression of maturation markers on bone marrow derived DCs. This
      observation correlated in vivo with an increased and accelerated expression of
      maturation markers on DCs in the draining lymph node upon HET immunization in
      mice. This effect was found to be independent of the antigen delivered and
      depends only on the thermal component of HET immunization. In vitro hyperthermia
      also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes
      the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell
      response. HET immunization also induced a systemic T cell response to TT, as
      suggested by proliferation of splenocytes from immunized animal upon in vitro
      stimulation by TT. Exposure to heat during primary immunization led to generation
      of mainly IgG class of antibodies upon boosting, similar to the use of
      conventional alum adjuvant, thus highlighting the adjuvant potential of heat
      during HET immunization. Lastly, we have shown that mice immunized by tetanus
      toxoid using HET route exhibited protection against challenge with a lethal dose
      of tetanus toxin. Thus, in addition to being a painless, needle free delivery
      system it also has an immune modulatory potential.

PMID- 22363799
TI  - Cell-type specific oxytocin gene expression from AAV delivered promoter deletion
      constructs into the rat supraoptic nucleus in vivo.
AB  - The magnocellular neurons (MCNs) in the hypothalamus selectively express either
      oxytocin (OXT) or vasopressin (AVP) neuropeptide genes, a property that defines
      their phenotypes. Here we examine the molecular basis of this selectivity in the
      OXT MCNs by stereotaxic microinjections of adeno-associated virus (AAV) vectors
      that contain various OXT gene promoter deletion constructs using EGFP as the
      reporter into the rat supraoptic nucleus (SON). Two weeks following injection of
      the AAVs, immunohistochemical assays of EGFP expression from these constructs
      were done to determine whether the EGFP reporter co-localizes with either the OXT
      or AVP-immunoreactivity in the MCNs. The results show that the key elements in
      the OT gene promoter that regulate the cell-type specific expression the SON are
      located -216 to -100 bp upstream of the transcription start site. We hypothesize
      that within this 116 bp domain a repressor exists that inhibits expression
      specifically in AVP MCNs, thereby leading to the cell-type specific expression of
      the OXT gene only in the OXT MCNs.

PMID- 22363800
TI  - A pivotal role of vitamin B9 in the maintenance of regulatory T cells in vitro
      and in vivo.
AB  - Dietary factors regulate immunological function, but the underlying mechanisms
      remain elusive. Here we show that vitamin B9 is a survival factor for regulatory
      T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4).
      In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from
      naive T cells but failed to survive. The impaired survival of Treg cells was
      associated with decreased expression of anti-apoptotic Bcl2 and independent of IL
      2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg
      cells in the small intestine, a site for the absorption of dietary vitamin B9.
      These findings provide a new link between diet and the immune system, which could
      maintain the immunological homeostasis in the intestine.

PMID- 22363801
TI  - The GOAT-ghrelin system is not essential for hypoglycemia prevention during
      prolonged calorie restriction.
AB  - OBJECTIVE: Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently
      been reported to be essential for the prevention of hypoglycemia during prolonged
      negative energy balance. Using a unique set of four different genetic loss-of
      function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR)
      system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or
      signaling would lead to hypoglycemia during caloric deprivation. METHODOLOGY:
      Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and
      GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum
      chow intake). Body weight, fat mass, and glucose levels were recorded daily and
      compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were
      generated for each individual mouse when 2% or less body fat mass was reached.
      Blood samples were obtained for analysis of circulating levels of acyl- and
      desacyl-ghrelin, IGF-1, and insulin. PRINCIPAL FINDINGS: Chronic calorie
      restriction progressively decreased body weight and body fat mass in all mice
      regardless of genotype. When fat mass was depleted to 2% or less of body weight
      for 2 consecutive days, random hypoglycemic events occurred in some mice across
      all genotypes. There was no increase in the incidence of hypoglycemia in any of
      the four loss-of-function models for ghrelin signaling including GOAT KO mice.
      Furthermore, no differences in insulin or IGF-1 levels were observed between
      genotypes. CONCLUSION: The endogenous GOAT-ghrelin-GHSR system is not essential
      for the maintenance of euglycemia during prolonged calorie restriction.

PMID- 22363802
TI  - HIV-1 inhibits phagocytosis and inflammatory cytokine responses of human monocyte
      derived macrophages to P. falciparum infected erythrocytes.
AB  - HIV-1 infection increases the risk and severity of malaria by poorly defined
      mechanisms. We investigated the effect of HIV-1(Ba-L) infection of monocyte
      derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected
      erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to
      mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE
      (median (IQR) (10 (0-28) versus (34 (27-108); IE internalised/100 MDM; p = 0.001)
      and decreased secretion of IL-6 (1,116 (352-3,387) versus 1,552 (889-6,331);
      pg/mL; p = 0.0078) and IL-1beta (16 (7-21) versus 33 (27-65); pg/mL; p = 0.0078).
      Thus inadequate phagocytosis and cytokine production may contribute to impaired
      control of malaria in HIV-1 infected individuals.

PMID- 22363803
TI  - Risk factors of Coxiella burnetii (Q fever) seropositivity in veterinary medicine
      students.
AB  - BACKGROUND: Q fever is an occupational risk for veterinarians, however little is
      known about the risk for veterinary medicine students. This study aimed to assess
      the seroprevalence of Coxiella burnetii among veterinary medicine students and to
      identify associated risk factors. METHODS: A cross-sectional study with
      questionnaire and blood sample collection was performed among all veterinary
      medicine students studying in The Netherlands in 2006. Serum samples (n = 674),
      representative of all study years and study directions, were analyzed for C.
      burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay
      (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1:32 and
      above. RESULTS: Of the veterinary medicine students 126 (18.7%) had IgG
      antibodies against C. burnetii. Seropositivity associated risk factors identified
      were the study direction 'farm animals' (Odds Ratio (OR) 3.27 [95% CI 2.14
      5.02]), advanced year of study (OR year 6: 2.31 [1.22-4.39] OR year 3-5 1.83
      [1.07-3.10]) having had a zoonosis during the study (OR 1.74 [1.07-2.82]) and
      ever lived on a ruminant farm (OR 2.73 [1.59-4.67]). Stratified analysis revealed
      study direction 'farm animals' to be a study-related risk factor apart from ever
      living on a farm. In addition we identified a clear dose-response relation for
      the number of years lived on a farm with C. burnetii seropositivity. CONCLUSIONS:
      C. burnetii seroprevalence is considerable among veterinary medicine students and
      study related risk factors were identified. This indicates Q fever as an
      occupational risk for veterinary medicine students.

PMID- 22363804
TI  - From local to global dilemmas in social networks.
AB  - Social networks affect in such a fundamental way the dynamics of the population
      they support that the global, population-wide behavior that one observes often
      bears no relation to the individual processes it stems from. Up to now, linking
      the global networked dynamics to such individual mechanisms has remained elusive.
      Here we study the evolution of cooperation in networked populations and let
      individuals interact via a 2-person Prisoner's Dilemma--a characteristic
      defection dominant social dilemma of cooperation. We show how homogeneous
      networks transform a Prisoner's Dilemma into a population-wide evolutionary
      dynamics that promotes the coexistence between cooperators and defectors, while
      heterogeneous networks promote their coordination. To this end, we define a
      dynamic variable that allows us to track the self-organization of cooperators
      when co-evolving with defectors in networked populations. Using the same
      variable, we show how the global dynamics--and effective dilemma--co-evolves with
      the motifs of cooperators in the population, the overall emergence of cooperation
      depending sensitively on this co-evolution.

PMID- 22363805
TI  - High CO2 and silicate limitation synergistically increase the toxicity of Pseudo
      nitzschia fraudulenta.
AB  - Anthropogenic CO(2) is progressively acidifying the ocean, but the responses of
      harmful algal bloom species that produce toxins that can bioaccumulate remain
      virtually unknown. The neurotoxin domoic acid is produced by the globally
      distributed diatom genus Pseudo-nitzschia. This toxin is responsible for amnesic
      shellfish poisoning, which can result in illness or death in humans and regularly
      causes mass mortalities of marine mammals and birds. Domoic acid production by
      Pseudo-nitzschia cells is known to be regulated by nutrient availability, but
      potential interactions with increasing seawater CO(2) concentrations are poorly
      understood. Here we present experiments measuring domoic acid production by
      acclimatized cultures of Pseudo-nitzschia fraudulenta that demonstrate a strong
      synergism between projected future CO(2) levels (765 ppm) and silicate-limited
      growth, which greatly increases cellular toxicity relative to growth under modern
      atmospheric (360 ppm) or pre-industrial (200 ppm) CO(2) conditions. Cellular Si:C
      ratios decrease with increasing CO(2), in a trend opposite to that seen for
      domoic acid production. The coastal California upwelling system where this
      species was isolated currently exhibits rapidly increasing levels of
      anthropogenic acidification, as well as widespread episodic silicate limitation
      of diatom growth. Our results suggest that the current ecosystem and human health
      impacts of toxic Pseudo-nitzschia blooms could be greatly exacerbated by future
      ocean acidification and 'carbon fertilization' of the coastal ocean.

PMID- 22363806
TI  - Activation of JNK signaling mediates connective tissue growth factor expression
      and scar formation in corneal wound healing.
AB  - Connective Tissue Growth Factor (CTGF) and Transforming growth factor-beta1 (TGF
      beta1) are key growth factors in regulating corneal scarring. Although CTGF was
      induced by TGF-beta1 and mediated many of fibroproliferative effects of TGF
      beta1, the signaling pathway for CTGF production in corneal scarring remains to
      be clarified. In the present study, we firstly investigated the effects of c-Jun
      N-terminal kinase (JNK) on CTGF expression induce by TGF-beta1 in Telomerase
      immortalized human cornea stroma fibroblasts (THSF). Then, we created penetrating
      corneal wound model and determined the effect of JNK in the pathogenesis of
      corneal scarring. TGF-beta1 activated MAPK pathways in THSF cells. JNK inhibitor
      significantly inhibited CTGF, fibronectin and collagen I expression induced by
      TGF-beta1 in THSF. In corneal wound healing, the JNK inhibitor significantly
      inhibited CTGF expression, markedly improved the architecture of corneal stroma
      and reduced corneal scar formation, but did not have a measurable impact on
      corneal wound healing in vivo. Our results indicate that JNK mediates the
      expression of CTGF and corneal scarring in corneal wound healing, and might be
      considered as specific targets of drug therapy for corneal scarring.

PMID- 22363807
TI  - Involvement of cyclin K posttranscriptional regulation in the formation of
      Artemia diapause cysts.
AB  - BACKGROUND: Artemia eggs tend to develop ovoviviparously to yield nauplius larvae
      in good rearing conditions; while under adverse situations, they tend to develop
      oviparously and encysted diapause embryos are formed instead. However, the
      intrinsic mechanisms regulating this process are not well understood. PRINCIPAL
      FINDING: This study has characterized the function of cyclin K, a regulatory
      subunit of the positive transcription elongation factor b (P-TEFb) in the two
      different developmental pathways of Artemia. In the diapause-destined embryo,
      Western blots showed that the cyclin K protein was down-regulated as the embryo
      entered dormancy and reverted to relatively high levels of expression once
      development resumed, consistent with the fluctuations in phosphorylation of
      position 2 serines (Ser2) in the C-terminal domain (CTD) of the largest subunit
      (Rpb1) of RNA polymerase II (RNAP II). Interestingly, the cyclin K transcript
      levels remained constant during this process. In vitro translation data indicated
      that the template activity of cyclin K mRNA stored in the postdiapause cyst was
      repressed. In addition, in vivo knockdown of cyclin K in developing embryos by
      RNA interference eliminated phosphorylation of the CTD Ser2 of RNAP II and
      induced apoptosis by inhibiting the extracellular signal-regulated kinase (ERK)
      survival signaling pathway. CONCLUSIONS/SIGNIFICANCE: Taken together, these
      findings reveal a role for cyclin K in regulating RNAP II activity during
      diapause embryo development, which involves the post-transcriptional regulation
      of cyclin K. In addition, a further role was identified for cyclin K in
      regulating the control of cell survival during embryogenesis through ERK
      signaling pathways.

PMID- 22363809
TI  - Monocyte gene expression signature of patients with early onset coronary artery
      disease.
AB  - The burden of cardiovascular disease (CVD) cannot be fully addressed by therapy
      targeting known pathophysiological pathways. Even with stringent control of all
      risk factors CVD events are only diminished by half. A number of additional
      pathways probably play a role in the development of CVD and might serve as novel
      therapeutic targets. Genome wide expression studies represent a powerful tool to
      identify such novel pathways. We compared the expression profiles in monocytes
      from twenty two young male patients with premature familial CAD with those from
      controls matched for age, sex and smoking status, without a family history of
      CVD. Since all patients were on statins and aspirin treatment, potentially
      affecting the expression of genes in monocytes, twelve controls were subsequently
      treated with simvastatin and aspirin for 6 and 2 weeks, respectively. By whole
      genome expression arrays six genes were identified to have differential
      expression in the monocytes of patients versus controls; ABCA1, ABCG1 and RGS1
      were downregulated in patients, whereas ADRB2, FOLR3 and GSTM1 were upregulated.
      Differential expression of all genes, apart from GSTM1, was confirmed by qPCR.
      Aspirin and statins altered gene expression of ABCG1 and ADBR2. All finding were
      validated in a second group of twenty four patients and controls. Differential
      expression of ABCA1, RSG1 and ADBR2 was replicated. In conclusion, we identified
      these 3 genes to be expressed differently in CAD cases which might play a role in
      the pathogenesis of atherosclerotic vascular disease.

PMID- 22363810
TI  - Alcohol consumption, genetic variants in alcohol deydrogenases, and risk of
      cardiovascular diseases: a prospective study and meta-analysis.
AB  - OBJECTIVE: First, to investigate and compare associations between alcohol
      consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of
      cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively
      summarize available evidence of prospective studies on polymorphisms in ADH1B and
      ADH1C and CVD-risk. METHODS: We conducted a case-cohort study nested within the
      European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
      cohort including a randomly drawn subcohort (n = 2175) and incident cases of
      myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was
      8.2+/-2.2 years. The association between alcohol consumption, ADH1B or ADH1C
      genotypes, and CVD-risk was assessed using Cox proportional hazards regression.
      Additionally, we report results on associations of variants in ADH1B and ADH1C
      with ischemic heart disease and stroke in the context of a meta-analysis of
      previously published prospective studies published up to November 2011. RESULTS:
      Compared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk
      of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10-0.97) and
      among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33-0.98) or >60 g
      alcohol/d (HR = 0.30; 95% CI: 0.12-0.78). Stroke risk was not significantly
      related to alcohol consumption >6 g/d, but we observed an increased risk of
      stroke in men reporting no alcohol consumption. Individuals with the slow-coding
      ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms
      in ADH1B or ADH1C were not significantly associated with risk of CVD in our data
      and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35
      (95% CI: 0.98-1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI:
      0.90-1.27; p for heterogeneity: 0.098)]. CONCLUSION: The well described
      association between alcohol consumption and CVD-risk is not reflected by ADH
      polymorphisms, which modify the rate of ethanol oxidation.

PMID- 22363808
TI  - Diversity measures in environmental sequences are highly dependent on alignment
      quality--data from ITS and new LSU primers targeting basidiomycetes.
AB  - The ribosomal DNA comprised of the ITS1-5.8S-ITS2 regions is widely used as a
      fungal marker in molecular ecology and systematics but cannot be aligned with
      confidence across genetically distant taxa. In order to study the diversity of
      Agaricomycotina in forest soils, we designed primers targeting the more alignable
      28S (LSU) gene, which should be more useful for phylogenetic analyses of the
      detected taxa. This paper compares the performance of the established ITS1F/4B
      primer pair, which targets basidiomycetes, to that of two new pairs. Key factors
      in the comparison were the diversity covered, off-target amplification,
      rarefaction at different Operational Taxonomic Unit (OTU) cutoff levels,
      sensitivity of the method used to process the alignment to missing data and
      insecure positional homology, and the congruence of monophyletic clades with OTU
      assignments and BLAST-derived OTU names. The ITS primer pair yielded no off
      target amplification but also exhibited the least fidelity to the expected
      phylogenetic groups. The LSU primers give complementary pictures of diversity,
      but were more sensitive to modifications of the alignment such as the removal of
      difficult-to align stretches. The LSU primers also yielded greater numbers of
      singletons but also had a greater tendency to produce OTUs containing sequences
      from a wider variety of species as judged by BLAST similarity. We introduced some
      new parameters to describe alignment heterogeneity based on Shannon entropy and
      the extent and contents of the OTUs in a phylogenetic tree space. Our results
      suggest that ITS should not be used when calculating phylogenetic trees from
      genetically distant sequences obtained from environmental DNA extractions and
      that it is inadvisable to define OTUs on the basis of very heterogeneous
      alignments.

PMID- 22363811
TI  - Complete mitochondrial DNA analysis of eastern Eurasian haplogroups rarely found
      in populations of northern Asia and eastern Europe.
AB  - With the aim of uncovering all of the most basal variation in the northern Asian
      mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and
      coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and
      149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence
      of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in
      Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of
      northern and central Asia has been revealed, reflecting both influences of
      central Asian inhabitants and essential genetic interaction with the Altai region
      indigenous populations. Statistical analyses data demonstrate a close positioning
      of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as
      well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their
      origin from a common maternal ancestral gene pool. In order to achieve a thorough
      coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we
      have completely sequenced the mtDNA of 55 samples representing haplogroups R11b,
      B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive
      collection (over 5000 individuals) of northern and eastern Asian, as well as
      European control region mtDNA sequences. Applying the newly updated mtDNA tree to
      the previously reported northern Asian and eastern Asian mtDNA data sets has
      resolved the status of the poorly classified mtDNA types and allowed us to obtain
      the coalescence age estimates of the nodes of interest using different calibrated
      rates. Our findings confirm our previous conclusion that northern Asian maternal
      gene pool consists of predominantly post-LGM components of eastern Asian
      ancestry, though some genetic lineages may have a pre-LGM/LGM origin.

PMID- 22363812
TI  - Regulation of axonal HCN1 trafficking in perforant path involves expression of
      specific TRIP8b isoforms.
AB  - The functions of HCN channels in neurons depend critically on their subcellular
      localization, requiring fine-tuned machinery that regulates subcellular channel
      trafficking. Here we provide evidence that regulatory mechanisms governing axonal
      HCN channel trafficking involve association of the channels with specific
      isoforms of the auxiliary subunit TRIP8b. In the medial perforant path, which
      normally contains HCN1 channels in axon terminals in immature but not in adult
      rodents, we found axonal HCN1 significantly increased in adult mice lacking
      TRIP8b (TRIP8b(-/-)). Interestingly, adult mice harboring a mutation that results
      in expression of only the two most abundant TRIP8b isoforms (TRIP8b[1b/2](-/-))
      exhibited an HCN1 expression pattern similar to wildtype mice, suggesting that
      presence of one or both of these isoforms (TRIP8b(1a), TRIP8b(1a-4)) prevents
      HCN1 from being transported to medial perforant path axons in adult mice.
      Concordantly, expression analyses demonstrated a strong increase of expression of
      both TRIP8b isoforms in rat entorhinal cortex with age. However, when
      overexpressed in cultured entorhinal neurons of rats, TRIP8b(1a), but not
      TRIP8b(1a-4), altered substantially the subcellular distribution of HCN1 by
      promoting somatodendritic and reducing axonal expression of the channels. Taken
      together, we conclude that TRIP8b isoforms are important regulators of HCN1
      trafficking in entorhinal neurons and that the alternatively-spliced isoform
      TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN
      channels out of perforant path axon terminals.

PMID- 22363813
TI  - Large fragment pre-S deletion and high viral load independently predict hepatitis
      B relapse after liver transplantation.
AB  - Hepatitis B virus (HBV) associated end-stage liver diseases are the leading
      causes of liver transplantation (LT) in Taiwan. Relapse of hepatitis B occurs
      after LT, raising the risk of graft failure and reducing patient survival.
      Although several oral antiviral agents have been approved for anti-HBV treatment,
      lamivudine (LAM) remained to be the most widely used preventive regimen in
      Taiwan. While several clinical predictors have been identified for hepatitis B
      relapse, the predictive roles of the histopathological characteristics in liver
      explants as well as the genotypic features of the viruses in pre-LT serum samples
      have not been assessed. Between September 2002 and August 2009, 150 consecutive
      hepatitis B surface antigen (HBsAg) positive patients undergoing LT were included
      for outcome analysis following assessment of the clinicopathological and
      virological factors prior to LT. Kaplan-Meier analyses discovered that pre
      operative LAM treatment <=3 months; membranous distribution and higher expression
      of tissue HBsAg in liver explants; preoperative viral load >=10(6) copies/ml; and
      presence of large fragment (>100 base pairs) pre-S deletion (LFpreSDel)
      correlated significantly with hepatitis B relapse. Multivariate Cox regression
      analysis showed that the presence of LFpreSDel (P = 0.001) and viral load >=10(6)
      copies/mL (P = 0.023) were independent predictors for hepatitis B relapse. In
      conclusion, besides high viral load, LFpreSDel mutation is an important
      independent predictor for hepatitis B relapse after LT. More aggressive
      preventive strategies should be applied for patients carrying these risk factors.

PMID- 22363814
TI  - Insulin-like growth factors promote vasculogenesis in embryonic stem cells.
AB  - The ability of embryonic stem cells to differentiate into endothelium and form
      functional blood vessels has been well established and can potentially be
      harnessed for therapeutic angiogenesis. However, after almost two decades of
      investigation in this field, limited knowledge exists for directing endothelial
      differentiation. A better understanding of the cellular mechanisms regulating
      vasculogenesis is required for the development of embryonic stem cell-based
      models and therapies. In this study, we elucidated the mechanistic role of
      insulin-like growth factors (IGF1 and 2) and IGF receptors (IGFR1 and 2) in
      endothelial differentiation using an embryonic stem cell embryoid body model.
      Both IGF1 or IGF2 predisposed embryonic stem to differentiate towards a
      mesodermal lineage, the endothelial precursor germ layer, as well as increased
      the generation of significantly more endothelial cells at later stages.
      Inhibition of IGFR1 signaling using neutralizing antibody or a pharmacological
      inhibitor, picropodophyllin, significantly reduced IGF-induced mesoderm and
      endothelial precursor cell formation. We confirmed that IGF-IGFR1 signaling
      stabilizes HIF1alpha and leads to up-regulation of VEGF during vasculogenesis in
      embryoid bodies. Understanding the mechanisms that are critical for
      vasculogenesis in various models will bring us one step closer to enabling cell
      based therapies for neovascularization.

PMID- 22363815
TI  - Tissue specific deletion of inhibitor of kappa B kinase 2 with OX40-Cre reveals
      the unanticipated expression from the OX40 locus in skin epidermis.
AB  - NF-kappaB signalling plays an essential role in T cell activation and generation
      of regulatory and memory populations in vivo. In the present study, we aimed to
      investigate the role of NF-kappaB signalling in post-activation T cells using
      tissue specific ablation of inhibitor of kappa-B kinase 2 expression, an
      important component of the inhibitor of kappa-B kinase complex in canonical NF
      kappaB signalling. The OX40 antigen is expressed on activated T cells. Therefore,
      we used previously described mouse strain expressing Cre recombinase from the
      endogenous OX40 locus. Ablation of IKK2 expression using OX40(Cre) mice resulted
      in the development of an inflammatory response in the skin epidermis causing wide
      spread skin lesions. The inflammatory response was characterised by extensive
      leukocytic infiltrate in skin tissue, hyperplasia of draining lymph nodes and
      widespread activation in the T cell compartment. Surprisingly, disease
      development did not depend on T cells but was rather associated with an
      unanticipated expression of Cre in skin epidermis, and activation of the T cell
      compartment did not require Ikbk2 deletion in T cells. Employment of Cre reporter
      strains revealed extensive Cre activity in skin epidermis. Therefore, development
      of skin lesions was rather more likely explained by deletion of Ikbk2 in skin
      keratinocytes in OX40(Cre) mice.

PMID- 22363816
TI  - Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin
      signaling pathway in cultured LPS-stimulated microglial cells.
AB  - BACKGROUND: Resveratrol have been known to possess many pharmacological
      properties including antioxidant, cardioprotective and anticancer effects.
      Although current studies indicate that resveratrol produces neuroprotection
      against neurological disorders, the precise mechanisms for its beneficial effects
      are still not fully understood. We investigate the effect of anti-inflammatory
      and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine
      microglial BV-2 cells. METHODOLOGY/PRINCIPAL FINDINGS: BV-2 cells were treated
      with resveratrol (25, 50, and 100 uM) and/or LPS (1 ug/ml). Nitric oxide (NO) and
      prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and
      protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR
      and double immunofluorescence labeling, respectively. Phosphorylation levels of
      PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian
      target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades,
      inhibitor kappaB-alpha (IkappaB-alpha) and cyclic AMP-responsive element-binding
      protein (CREB) were measured by western blot. Resveratrol significantly
      attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide
      synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta) and nuclear factor-kappaB (NF-kappaB) in BV
      2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose
      dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR
      inhibitor, blocked the effects of resveratrol on LPS-induced microglial
      activation. In addition, mTOR inhibition partially abolished the inhibitory
      effect of resveratrol on the phosphorylation of IkappaB-alpha, CREB,
      extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein
      kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). CONCLUSION AND
      IMPLICATIONS: This study indicates that resveratrol inhibited LPS-induced
      proinflammatory enzymes and proinflammatory cytokines via down-regulation
      phosphorylation of NF-kappaB, CREB and MAPKs family in a mTOR-dependent manner.
      These findings reveal, in part, the molecular basis underlying the anti
      inflammatory properties of resveratrol.

PMID- 22363817
TI  - Matrix-bound PAI-1 supports cell blebbing via RhoA/ROCK1 signaling.
AB  - The microenvironment of a tumor can influence both the morphology and the
      behavior of cancer cells which, in turn, can rapidly adapt to environmental
      changes. Increasing evidence points to the involvement of amoeboid cell migration
      and thus of cell blebbing in the metastatic process; however, the cues that
      promote amoeboid cell behavior in physiological and pathological conditions have
      not yet been clearly identified. Plasminogen Activator Inhibitor type-1 (PAI-1)
      is found in high amount in the microenvironment of aggressive tumors and is
      considered as an independent marker of bad prognosis. Here we show by
      immunoblotting, activity assay and immunofluorescence that, in SW620 human
      colorectal cancer cells, matrix-associated PAI-1 plays a role in the cell
      behavior needed for amoeboid migration by maintaining cell blebbing, localizing
      PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway
      activation. The results obtained by modeling PAI-1 deposition around tumors
      indicate that matrix-bound PAI-1 is heterogeneously distributed at the tumor
      periphery and that, at certain spots, the elevated concentrations of matrix-bound
      PAI-1 needed for cancer cells to undergo the mesenchymal-amoeboid transition can
      be observed. Matrix-bound PAI-1, as a matricellular protein, could thus represent
      one of the physiopathological requirements to support metastatic formation.

PMID- 22363818
TI  - High affinity antibodies to Plasmodium falciparum merozoite antigens are
      associated with protection from malaria.
AB  - BACKGROUND: Malaria kills almost 1 million people every year, but the mechanisms
      behind protective immunity against the disease are still largely unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, surface plasmon resonance
      technology was used to evaluate the affinity (measured as k(d)) of naturally
      acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1.
      Antibodies in serum samples from residents in endemic areas bound with higher
      affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of
      MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7
      increased with age, and were usually within similar range as the affinities for
      the monoclonal antibodies also examined in this study. The finding of MSP2-3D7
      type parasites in the blood was associated with a tendency for higher affinity
      antibodies to both forms of MSP2 and AMA1, but this was significant only when
      analyzing antibodies against MSP2-FC27, and individuals infected with both
      allelic forms of MSP2 at the same time showed the highest affinities. Individuals
      with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged
      time to clinical malaria during 40 weeks of follow-up, and among individuals who
      were parasite positive at baseline higher antibody affinities to all antigens
      were seen in the individuals that did not experience febrile malaria during
      follow up. CONCLUSIONS/SIGNIFICANCE: This study contributes important information
      for understanding how immunity against malaria arises. The findings suggest that
      antibody affinity plays an important role in protection against disease, and
      differs between antigens. In light of this information, antibody affinity
      measurements would be a key assessment in future evaluation of malaria vaccine
      formulations.

PMID- 22363819
TI  - Identification of putative potassium channel homologues in pathogenic protozoa.
AB  - K(+) channels play a vital homeostatic role in cells and abnormal activity of
      these channels can dramatically alter cell function and survival, suggesting that
      they might be attractive drug targets in pathogenic organisms. Pathogenic
      protozoa lead to diseases such as malaria, leishmaniasis, trypanosomiasis and
      dysentery that are responsible for millions of deaths each year worldwide. The
      genomes of many protozoan parasites have recently been sequenced, allowing
      rational design of targeted therapies. We analyzed the genomes of pathogenic
      protozoa and show the existence within them of genes encoding putative homologues
      of K(+) channels. These protozoan K(+) channel homologues represent novel targets
      for anti-parasitic drugs. Differences in the sequences and diversity of human and
      parasite proteins may allow pathogen-specific targeting of these K(+) channel
      homologues.

PMID- 22363820
TI  - A bispecific antibody based assay shows potential for detecting tuberculosis in
      resource constrained laboratory settings.
AB  - The re-emergence of tuberculosis (TB) as a global public health threat highlights
      the necessity of rapid, simple and inexpensive point-of-care detection of the
      disease. Early diagnosis of TB is vital not only for preventing the spread of the
      disease but also for timely initiation of treatment. The later in turn will
      reduce the possible emergence of multi-drug resistant strains of Mycobacterium
      tuberculosis. Lipoarabinomannan (LAM) is an important non-protein antigen of the
      bacterial cell wall, which is found to be present in different body fluids of
      infected patients including blood, urine and sputum. We have developed a
      bispecific monoclonal antibody with predetermined specificities towards the LAM
      antigen and a reporter molecule horseradish peroxidase (HRPO). The developed
      antibody was subsequently used to design a simple low cost immunoswab based assay
      to detect LAM antigen. The limit of detection for spiked synthetic LAM was found
      to be 5.0 ng/ml (bovine urine), 0.5 ng/ml (rabbit serum) and 0.005 ng/ml (saline)
      and that for bacterial LAM from M. tuberculosis H37Rv was found to be 0.5 ng/ml
      (rabbit serum). The assay was evaluated with 21 stored clinical serum samples (14
      were positive and 7 were negative in terms of anti-LAM titer). In addition, all
      14 positive samples were culture positive. The assay showed 100% specificity and
      64% sensitivity (95% confidence interval). In addition to good specificity, the
      end point could be read visually within two hours of sample collection. The
      reported assay might be used as a rapid tool for detecting TB in resource
      constrained laboratory settings.

PMID- 22363821
TI  - Contribution of a genomic accessory region encoding a putative cellobiose
      phosphotransferase system to virulence of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae (the pneumococcus) is a formidable human pathogen,
      responsible for massive global morbidity and mortality. The ability to utilize
      carbohydrates in a variety of host niches appears to be integral to pneumococcal
      pathogenesis. In this study we investigated a genomic island, which includes a
      ROK family protein, a putative cellobiose phosphotransferase system (PTS) and a
      putative sulfatase. This accessory region is widespread in the pneumococcus in
      strains of various serotypes and levels of virulence. We have performed simple
      bioinformatic analysis of the region and investigated its role in vivo in 2
      strains with markedly different virulence profiles (WCH206 of serotype 3, ST180;
      Menzies5 of serotype 11A, ST662). Deleting and replacing the entire island with
      an antibiotic resistance cassette caused the virulent serotype 3 strain to become
      attenuated in a murine pneumonia/sepsis model. Further mutants were constructed
      and used to show that various components of the island contribute significantly
      to the fitness of WCH206 in a variety of niches of this model, including the
      nasopharynx, ears and blood, but especially in the lungs. In addition, the island
      conferred a competitive advantage in nasopharyngeal colonization for the serotype
      11A strain, which was essentially avirulent in the pneumonia/sepsis model. The
      contribution of this island to both pathogenesis and colonization may explain why
      this accessory region is widespread in the pneumococcus.

PMID- 22363822
TI  - Spatial dimensions of dengue virus transmission across interepidemic and epidemic
      periods in Iquitos, Peru (1999-2003).
AB  - BACKGROUND: Knowledge of spatial patterns of dengue virus (DENV) infection is
      important for understanding transmission dynamics and guiding effective disease
      prevention strategies. Because movement of infected humans and mosquito vectors
      plays a role in the spread and persistence of virus, spatial dimensions of
      transmission can range from small household foci to large community clusters.
      Current understanding is limited because past analyses emphasized clinically
      apparent illness and did not account for the potentially large proportion of
      inapparent infections. In this study we analyzed both clinically apparent and
      overall infections to determine the extent of clustering among human DENV
      infections. METHODOLOGY/PRINCIPAL FINDINGS: We conducted spatial analyses at
      global and local scales, using acute case and seroconversion data from a
      prospective longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began
      during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned
      to epidemic DENV-3 transmission. Infection status was determined by
      seroconversion based on plaque neutralization testing of sequential blood samples
      taken at approximately six-month intervals, with date of infection assigned as
      the middate between paired samples. Each year was divided into three distinct
      seasonal periods of DENV transmission. Spatial heterogeneity was detected in
      baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence
      calculated by trimester from 2001-2003 was spatially similar to preexisting DENV
      1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K
      statistic) appeared at radii of ~200-800 m. Local analyses (Kuldorf spatial scan
      statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The
      number of seroconversions per cluster ranged from 3-34 with radii from zero (a
      single household) to 750 m; 65% of clusters had radii >100 m. No clustering was
      detected among clinically apparent infections. CONCLUSIONS/SIGNIFICANCE:
      Seroprevalence of previously circulating DENV serotypes can be a predictor of
      transmission risk for a different invading serotype and, thus, identify targets
      for strategically placed surveillance and intervention. Seroprevalence of a
      specific serotype is also important, but does not preclude other contributing
      factors, such as mosquito density, in determining where transmission of that
      virus will occur. Regardless of the epidemiological context or virus serotype,
      human movement appears to be an important factor in defining the spatial
      dimensions of DENV transmission and, thus, should be considered in the design and
      evaluation of surveillance and intervention strategies.

PMID- 22363823
TI  - Evaluation of the human IgG antibody response to Aedes albopictus saliva as a new
      specific biomarker of exposure to vector bites.
AB  - BACKGROUND: The spread of Aedes albopictus, a vector for re-emergent arbovirus
      diseases like chikungunya and dengue, points up the need for better control
      strategies and new tools to evaluate transmission risk. Human antibody (Ab)
      responses to mosquito salivary proteins could represent a reliable biomarker for
      evaluating human-vector contact and the efficacy of control programs.
      METHODOLOGY/PRINCIPAL FINDINGS: We used ELISA tests to evaluate specific
      immunoglobulin G (IgG) responses to salivary gland extracts (SGE) in adults
      exposed to Aedes albopictus in Reunion Island. The percentage of immune
      responders (88%) and levels of anti-SGE IgG Abs were high in exposed individuals.
      At an individual level, our results indicate heterogeneity of the exposure to
      Aedes albopictus bites. In addition, low-level immune cross-reactivity between
      Aedes albopictus and Aedes aegypti SGEs was observed, mainly in the highest
      responders. CONCLUSION/SIGNIFICANCE: Ab responses to saliva could be used as an
      immuno-epidemiological tool for evaluating exposure to Aedes albopictus bites.
      Combined with entomological and epidemiological methods, a "salivary" biomarker
      of exposure to Aedes albopictus could enhance surveillance of its spread and the
      risk of arbovirus transmission, and could be used as a direct tool for the
      evaluation of Aedes albopictus control strategies.

PMID- 22363824
TI  - Association of mast cell-derived VEGF and proteases in Dengue shock syndrome.
AB  - BACKGROUND: Recent in-vitro studies have suggested that mast cells are involved
      in Dengue virus infection. To clarify the role of mast cells in the development
      of clinical Dengue fever, we compared the plasma levels of several mast cell
      derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF
      receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and
      -17) between patients with differing severity of Dengue fever and healthy
      controls. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed at Children's
      Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from
      2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue
      hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the
      World Health Organization criteria. There were 189 healthy subjects, and 19
      febrile illness patients of the same Kinh ethnicity. The levels of mast cell
      derived mediators and -related cytokines in plasma were measured by ELISA. VEGF
      and sVEGFR-1 levels were significantly increased in DHF and DSS compared with
      those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in
      DHF and DSS. Significant increases in tryptase and chymase levels, which were
      accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS
      patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned
      to similar levels as DF and controls. In-vitro VEGF production by mast cells was
      examined in KU812 and HMC-1 cells, and was found to be highest when the cells
      were inoculated with Dengue virus and human Dengue virus-immune serum in the
      presence of IL-9. CONCLUSIONS: As mast cells are an important source of VEGF,
      tryptase, and chymase, our findings suggest that mast cell activation and mast
      cell-derived mediators participate in the development of DHF. The two proteases,
      particularly chymase, might serve as good predictive markers of Dengue disease
      severity.

PMID- 22363825
TI  - Cell death and reproductive regression in female Schistosoma mansoni.
AB  - The vitellarium is a highly proliferative organ, producing cells which are
      incorporated along with a fertilized ovum into the schistosome egg. Vitellarial
      growth fails to occur in virgin female schistosomes in single sex (female-only)
      infections, and involution of this tissue, which is accompanied by physical
      shrinkage of the entire worm, occurs when mature females sexually regress upon
      removal from their male partners. We have found that upon removal from their
      hosts into tissue culture, female parasites regress whether they are mated or
      not, but that cessation of egg production and a decline in expression of the
      vitelline gene p14 is delayed by mating. We used BrdU labeling to investigate
      whether there was a loss of proliferation in the vittelarium that might account
      for regression and found that the proliferation rate declined equally in paired
      and singled females once placed into culture. However, TUNEL staining and Caspase
      3 activity measurements indicate that the loss of vitrellarial cellularity
      associated with regression is associated with profound apoptotic vitelline cell
      death, which is not apparent in the vitellaria of paired females immediately ex
      vivo, and which develops in vitro regardless of whether males are present or not.
      Furthermore, primordial vitellaria in virgin females have a high frequency of
      apoptotic cells but are characterized by a proliferation rate that is
      indistinguishable from that in fully developed vitellaria in mature paired
      females. Taken together, our data suggest that the vitelline proliferation rate
      is independent of pairing status. In contrast, the survival of vitelline cells,
      and therefore the development of the vitellarium, is highly male-dependent. Both
      processes are negatively affected by removal from the host regardless of whether
      male worms are present or not, and are unsustainable using standard tissue
      culture approaches.

PMID- 22363826
TI  - Excretory/secretory-products of Echinococcus multilocularis larvae induce
      apoptosis and tolerogenic properties in dendritic cells in vitro.
AB  - BACKGROUND: Alveolar echinococcosis, caused by Echinococcus multilocularis
      larvae, is a chronic disease associated with considerable modulation of the host
      immune response. Dendritic cells (DC) are key effectors in shaping the immune
      response and among the first cells encountered by the parasite during an
      infection. Although it is assumed that E.multilocularis, by excretory/secretory
      (E/S)-products, specifically affects DC to deviate immune responses, little
      information is available on the molecular nature of respective E/S-products and
      their mode of action. METHODOLOGY/PRINCIPAL FINDINGS: We established cultivation
      systems for exposing DC to live material from early (oncosphere), chronic
      (metacestode) and late (protoscolex) infectious stages. When co-incubated with
      Echinococcus primary cells, representing the invading oncosphere, or metacestode
      vesicles, a significant proportion of DC underwent apoptosis and the surviving DC
      failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation
      markers and did not undergo apoptosis. After pre-incubation with primary cells
      and metacestode vesicles, DC showed a strongly impaired ability to be activated
      by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex
      E/S-products. While none of the larvae induced the secretion of pro-inflammatory
      IL-12p70, the production of immunosuppressive IL-10 was elevated in response to
      primary cell E/S-products. Finally, upon incubation with DC and naive T-cells,
      E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T
      cells in vitro. CONCLUSIONS: This is the first report on the induction of
      apoptosis in DC by cestode E/S-products. Our data indicate that the early
      infective stage of E. multilocularis is a strong inducer of tolerance in DC,
      which is most probably important for generating an immunosuppressive environment
      at an infection phase in which the parasite is highly vulnerable to host attacks.
      The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products
      suggests that these cells fulfill an important role for parasite persistence
      during chronic echinococcosis.

PMID- 22363827
TI  - Estimating the non-monetary burden of neurocysticercosis in Mexico.
AB  - BACKGROUND: Neurocysticercosis (NCC) is a major public health problem in many
      developing countries where health education, sanitation, and meat inspection
      infrastructure are insufficient. The condition occurs when humans ingest eggs of
      the pork tapeworm Taenia solium, which then develop into larvae in the central
      nervous system. Although NCC is endemic in many areas of the world and is
      associated with considerable socio-economic losses, the burden of NCC remains
      largely unknown. This study provides the first estimate of disability adjusted
      life years (DALYs) associated with NCC in Mexico. METHODS: DALYs lost for
      symptomatic cases of NCC in Mexico were estimated by incorporating morbidity and
      mortality due to NCC-associated epilepsy, and morbidity due to NCC-associated
      severe chronic headaches. Latin hypercube sampling methods were employed to
      sample the distributions of uncertain parameters and to estimate 95% credible
      regions (95% CRs). FINDINGS: In Mexico, 144,433 and 98,520 individuals are
      estimated to suffer from NCC-associated epilepsy and NCC-associated severe
      chronic headaches, respectively. A total of 25,341 (95% CR: 12,569-46,640) DALYs
      were estimated to be lost due to these clinical manifestations, with 0.25 (95%
      CR: 0.12-0.46) DALY lost per 1,000 person-years of which 90% was due to NCC
      associated epilepsy. CONCLUSION: This is the first estimate of DALYs associated
      with NCC in Mexico. However, this value is likely to be underestimated since only
      the clinical manifestations of epilepsy and severe chronic headaches were
      included. In addition, due to limited country specific data, some parameters used
      in the analysis were based on systematic reviews of the literature or primary
      research from other geographic locations. Even with these limitations, our
      estimates suggest that healthy years of life are being lost due to NCC in Mexico.

PMID- 22363829
TI  - Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary pre-fatal
      clinical and laboratory manifestations.
AB  - BACKGROUND: A better description of the clinical and laboratory manifestations of
      fatal patients with dengue hemorrhagic fever (DHF) is important in alerting
      clinicians of severe dengue and improving management. METHODS AND FINDINGS: Of
      309 adults with DHF, 10 fatal patients and 299 survivors (controls) were
      retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal
      (GI) bleeding was found in 4 patients, dengue shock syndrome (DSS) alone in 2;
      DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia,
      ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis
      bacteremia each in one. Fatal patients were found to have significantly higher
      frequencies of early altered consciousness (<=24 h after hospitalization),
      hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia
      with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid
      hemorrhage. Among those experienced early altered consciousness, massive GI
      bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae
      meningitis/bacteremia were each found in one patient. Significantly higher
      proportion of bandemia from initial (arrival) laboratory data in fatal patients
      as compared to controls, and higher proportion of pre-fatal leukocytosis and
      lower pre-fatal platelet count as compared to initial laboratory data of fatal
      patients were found. Massive GI bleeding (33.3%) and bacteremia (25%) were the
      major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the
      patients with pre-fatal profound thrombocytopenia (<20,000/uL), and 50% of the
      patients with pre-fatal prothrombin time (PT) prolongation experienced massive GI
      bleeding. CONCLUSIONS: Our report highlights causes of fatality other than DSS in
      patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia
      may be warning signs of severe dengue. Clinicians should be alert to the
      potential development of massive GI bleeding, particularly in patients with early
      altered consciousness, profound thrombocytopenia, prolonged PT and/or
      leukocytosis. Antibiotic(s) should be empirically used for patients at risk for
      bacteremia until it is proven otherwise, especially in those with early altered
      consciousness and leukocytosis.

PMID- 22363828
TI  - Envenomations by Bothrops and Crotalus snakes induce the release of mitochondrial
      alarmins.
AB  - Skeletal muscle necrosis is a common manifestation of viperid snakebite
      envenomations. Venoms from snakes of the genus Bothrops, such as that of B.
      asper, induce muscle tissue damage at the site of venom injection, provoking
      severe local pathology which often results in permanent sequelae. In contrast,
      the venom of the South American rattlesnake Crotalus durissus terrificus, induces
      a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with
      neurotoxicity. It is known that molecules released from damaged muscle might act
      as 'danger' signals. These are known as 'alarmins', and contribute to the
      inflammatory reaction by activating the innate immune system. Here we show that
      the venoms of B. asper and C. d. terrificus release the mitochondrial markers
      mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space,
      from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar
      extent by the two venoms whereas B. asper venom induced the release of higher
      amounts of mtDNA, thus reflecting hitherto some differences in their pathological
      action on muscle mitochondria. At variance, injection of these venoms in mice
      resulted in a different time-course of mtDNA release, with B. asper venom
      inducing an early onset increment in plasma levels and C. d. terrificus venom
      provoking a delayed release. We suggest that the release of mitochondrial
      'alarmins' might contribute to the local and systemic inflammatory events
      characteristic of snakebite envenomations.

PMID- 22363830
TI  - First human rabies case in French Guiana, 2008: epidemiological investigation and
      control.
AB  - BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On
      28 May 2008, the French National Reference Center for Rabies (Institut Pasteur,
      Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain
      reaction on skin biopsy and saliva specimens from a Guianan, who had never
      travelled overseas and died in Cayenne after presenting clinically typical
      meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the
      virus identified a Lyssavirus (Rabies virus species), closely related to those
      circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A
      multidisciplinary Crisis Unit was activated. Its objectives were to implement an
      epidemiological investigation and a veterinary survey, to provide control
      measures and establish a communications program. The origin of the contamination
      was not formally established, but was probably linked to a bat bite based on the
      virus type isolated. After confirming exposure of 90 persons, they were
      vaccinated against rabies: 42 from the case's entourage and 48 healthcare
      workers. To handle that emergence and the local population's increased demand to
      be vaccinated, a specific communications program was established using several
      media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode,
      occurring in the context of a Department far from continental France, strongly
      affected the local population, healthcare workers and authorities, and the
      management team faced intense pressure. This observation confirms that the risk
      of contracting rabies in French Guiana is real, with consequences for population
      educational program, control measures, medical diagnosis and post-exposure
      prophylaxis.

PMID- 22363831
TI  - Clear genetic distinctiveness between human- and pig-derived Trichuris based on
      analyses of mitochondrial datasets.
AB  - The whipworm, Trichuris trichiura, causes trichuriasis in ~600 million people
      worldwide, mainly in developing countries. Whipworms also infect other animal
      hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and
      cause disease in these hosts, which is similar to trichuriasis of humans.
      Although Trichuris species are considered to be host specific, there has been
      considerable controversy, over the years, as to whether T. trichiura and T. suis
      are the same or distinct species. Here, we characterised the entire mitochondrial
      genomes of human-derived Trichuris and pig-derived Trichuris, compared them and
      then tested the hypothesis that the parasites from these two host species are
      genetically distinct in a phylogenetic analysis of the sequence data. Taken
      together, the findings support the proposal that T. trichiura and T. suis are
      separate species, consistent with previous data for nuclear ribosomal DNA. Using
      molecular analytical tools, employing genetic markers defined herein, future work
      should conduct large-scale studies to establish whether T. trichiura is found in
      pigs and T. suis in humans in endemic regions.

PMID- 22363832
TI  - Epidemiology of Invasive Fungal Infections in Latin America.
AB  - The pathogenic role of invasive fungal infections (IFIs) has increased during the
      past two decades in Latin America and worldwide, and the number of patients at
      risk has risen dramatically. Working habits and leisure activities have also been
      a focus of attention by public health officials, as endemic mycoses have provoked
      a number of outbreaks. An extensive search of medical literature from Latin
      America suggests that the incidence of IFIs from both endemic and opportunistic
      fungi has increased. The increase in endemic mycoses is probably related to
      population changes (migration, tourism, and increased population growth), whereas
      the increase in opportunistic mycoses may be associated with the greater number
      of people at risk. In both cases, the early and appropriate use of diagnostic
      procedures has improved diagnosis and outcome.

PMID- 22363833
TI  - Antioxidant capacity of lenses with age-related cataract.
AB  - The immediate cause of the occurrence of cataract is unknown, but oxidative
      damage and effects of reactive oxygen species are considered important in its
      etiopathogenesis. Our research was aimed at testing the nonenzyme antioxidant
      power of corticonuclear lens blocks, with different types and different maturity
      of age-related cataract. Clinical and biochemical researches were carried out in
      101 patients with age-related cataract. In corticonuclear lens blocks of the
      patient, the concentration of nonprotein and total-SH groups and the
      concentration of total vitamin C and dehydroascorbic acid (DHA) were determined;
      the current redox balance of dehydroascorbate/ascorbate and total antioxidant
      power measured by ferric-reducing ability were examined. In corticonuclear lens
      blocks with incipient cataract a significantly higher concentration of GSH, total
      SH groups, concentration of total vitamin C and ascorbic acid (AA), and ferric
      reducing ability were measured. The measured concentration of DHA is higher than
      the concentration of AA in the lenses with the incipient and mature cataract. The
      concentration ratio of redox couple DHA/AA is higher in lenses with mature
      cataract, where the measured concentration of AA was lower than in the incipient
      cataract. Timely removal of DHA from the lens is important because of its
      potential toxicity as an oxidant. An increase of the current concentration of
      DHA/AA redox balance can be an indicator of oxidative stress.

PMID- 22363835
TI  - Integrity of the oral tissues in patients with solid-organ transplants.
AB  - The relationship between the use of immunosuppressants in solid-organ transplant
      patients and oral tissue abnormalities has been recognized. The objective of this
      study was to determine the state of oral tissue integrity in renal, heart, and
      liver transplant patients who are on continuous medical and dental control. Forty
      patients of both sexes were clinically evaluated at the Clinical Hospital of the
      University of Chile to identify pathologies of oral mucosa, gingival enlargement
      (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average
      age of the transplant subjects was 49.4 years, and the age range was 19 to 69
      years. Most subjects maintained a good level of oral hygiene, and the rate mean
      of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low
      (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was
      low despite the fact that these patients were immunosuppressed. Care and
      continuous monitoring seem to be of vital importance in maintaining the oral
      health of transplant patients.

PMID- 22363834
TI  - Training the brain to overcome the effect of aging on the human eye.
AB  - Presbyopia, from the Greek for aging eye, is, like death and taxes, inevitable.
      Presbyopia causes near vision to degrade with age, affecting virtually everyone
      over the age of 50. Presbyopia has multiple negative effects on the quality of
      vision and the quality of life, due to limitations on daily activities - in
      particular, reading. In addition presbyopia results in reduced near visual
      acuity, reduced contrast sensitivity, and slower processing speed. Currently
      available solutions, such as optical corrections, are not ideal for all daily
      activities. Here we show that perceptual learning (repeated practice on a
      demanding visual task) results in improved visual performance in presbyopes,
      enabling them to overcome and/or delay some of the disabilities imposed by the
      aging eye. This improvement was achieved without changing the optical
      characteristics of the eye. The results suggest that the aging brain retains
      enough plasticity to overcome the natural biological deterioration with age.

PMID- 22363836
TI  - In vivo molecular imaging in retinal disease.
AB  - There is an urgent need for early diagnosis in medicine, whereupon effective
      treatments could prevent irreversible tissue damage. The special structure of the
      eye provides a unique opportunity for noninvasive light-based imaging of ocular
      fundus vasculature. To detect endothelial injury at the early and reversible
      stage of adhesion molecule upregulation, some novel imaging agents that target
      retinal endothelial molecules were generated. In vivo molecular imaging has a
      great potential to impact medicine by detecting diseases or screening disease in
      early stages, identifying extent of disease, selecting disease and patient
      specific therapeutic treatment, applying a directed or targeted therapy, and
      measuring molecular-specific effects of treatment. Current preclinical findings
      and advances in instrumentation such as endoscopes and microcatheters suggest
      that these molecular imaging modalities have numerous clinical applications and
      will be translated into clinical use in the near future.

PMID- 22363837
TI  - Effects of fluorescein staining on laser in vivo confocal microscopy images of
      the cornea.
AB  - This study was designed to identify whether topical fluorescein, a common
      ophthalmic tool, affects laser in vivo confocal microscopy of the cornea, a tool
      with growing applications. Twenty-five eye care specialists were asked to
      identify presence or absence of fluorescein in 99 confocal micrographs of healthy
      corneas. Responses were statistically similar to guessing for the epithelium (48%
      +/- 14% of respondents correct per image) and the subbasal nerve plexus (49% +/-
      11% correct), but results were less clear for the stroma. Dendritic immune cells
      were quantified in bilateral images from subjects who had been unilaterally
      stained with fluorescein. Density of dendritic immune cells was statistically
      similar between the unstained and contralateral stained eyes of 24 contact lens
      wearers (P = .72) and of 10 nonwearers (P = .53). Overall, the results indicated
      that fluorescein staining did not interfere with laser confocal microscopy of
      corneal epithelium, subbasal nerves, or dendritic immune cells.

PMID- 22363838
TI  - Present status and perspectives on the use of alkylresorcinols as biomarkers of
      wholegrain wheat and rye intake.
AB  - Alkylresorcinols (ARs) were first proposed as potential biomarkers of wholegrain
      wheat and rye intake a decade ago. Since then there has been a considerable body
      of research which suggests that ARs do meet most criteria of a biomarker of these
      foods. Results from human studies on plasma AR and their plasma and urinary
      metabolites strongly indicate that these compounds are responsive to whole grain
      wheat and rye intake and are correlated with various measures of AR consumption.
      This review briefly summarises work on the bioactivities of AR and focuses on
      aspects related to their use as biomarkers of whole grain wheat and rye intake.
      Evidence suggests that they thus far broadly fulfil the criteria to act as
      biomarkers of these cereals. However, there are still gaps in the knowledge on
      factors relating to the wide interindividual variation, and application to
      different epidemiological cohorts. Overall, ARs are highly promising biomarkers
      of whole grain wheat and rye intake and add to our increasing understanding of
      whole grains and health.

PMID- 22363839
TI  - The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-beta-Induced
      Epithelial-Mesenchymal Transition.
AB  - The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret
      external signals and respond appropriately, especially during the epithelial
      mesenchymal transition (EMT). EMT is an important process during embryonic
      development, fibrosis, and tumor progression in which epithelial cells acquire
      mesenchymal, fibroblast-like properties and show reduced intercellular adhesion
      and increased motility. TGF-beta signaling is the first pathway to be described
      as an inducer of EMT, and its relationship with the Smad family is already well
      characterized. Studies of four members of the MAPK family in different biological
      systems have shown that the MAPK and TGF-beta signaling pathways interact with
      each other and have a synergistic effect on the secretion of additional growth
      factors and cytokines that in turn promote EMT. In this paper, we present
      background on the regulation and function of MAPKs and their cascades, highlight
      the mechanisms of MAPK crosstalk with TGF-beta signaling, and discuss the roles
      of MAPKs in EMT.

PMID- 22363840
TI  - Neuromyelitis optica: an antibody-mediated disorder of the central nervous
      system.
AB  - Neuromyelitis optica (NMO) is a recurrent inflammatory disease that
      preferentially targets the optic nerves and spinal cord leading to blindness and
      paralysis. The hallmarks of NMO include bilateral optic neuritis and
      longitudinally extensive transverse myelitis. Woman and African Americans are
      overrepresented in the US patient population. NMO is associated with the NMO-IgG
      biomarker, which targets the aquaporin-4 water channel on astrocytes. The humoral
      pathology of NMO lesions include IgG and IgM deposits and infiltration by
      granulocytes suggesting that the NMO-IgG may be involved in the pathogenesis of
      disease. This review of the recent NMO literature covers the clinical features,
      epidemiology, radiology and pathology of disease and includes discussion of the
      important basic science research work in the field.

PMID- 22363842
TI  - The Safety of EXPAREL (r) (Bupivacaine Liposome Injectable Suspension)
      Administered by Peripheral Nerve Block in Rabbits and Dogs.
AB  - A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15
      mg/mL) is currently being investigated for postsurgical analgesia via peripheral
      nerve block (PNB). Single-dose toxicology studies of EXPAREL (9, 18, and 30
      mg/kg), bupivacaine solution (Bsol, 9 mg/kg), and saline injected around the
      brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints
      included clinical pathology, pharmacokinetics, and histopathology evaluation on
      Day 3 and Day 15 (2/sex/group/period). EXPAREL resulted in a nearly 4-fold lower
      C(max) versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30
      mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous
      inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24
      dogs) in the brachial plexus sites. The results indicate that EXPAREL was well
      tolerated in these models and did not produce nerve damage after PNB in rabbits
      and dogs.

PMID- 22363843
TI  - Histocompatibility and long-term results of the follicular unit-like wigs after
      xenogeneic hair transplantation: an experimental study in rabbits.
AB  - Objective. This study was designed to observe the histocompatibility and long
      term results of wigs after xenogeneic hair transplantation and to explore the
      possibility of industrial products in clinical application. Methods. The human
      hair and melted medical polypropylene were preceded into the follicular unit-like
      wigs according to the natural follicular unit by extrusion molding. 12 New
      Zealand rabbits were used as experimental animals for wigs transplantation. The
      histocompatibility of polypropylene and human hair was observed by H&E staining
      and scanning electron microscope. The loss rate of wigs was calculated to
      evaluate the long-term result after transplantation. Results. Mild infiltration
      by inflammatory cells around the polypropylene and human hair were seen during
      the early period after transplantation, accompanied with local epithelial cell
      proliferation. The inflammatory cells were decreased after 30 days with increased
      collagen fibers around the polypropylene and human hair. The follicular unit-like
      wigs maintained a good histocompatibility in one year. The degradation of hair
      was not significant. The loss rate of wigs was 4.1 +/- 4.0% in one year. The
      appearance of hair was satisfactory. Conclusions. We successfully developed a
      follicular unit-like wigs, which were made of xenogeneic human hair with medical
      polypropylene, showing a good histocompatibility, a low loss rate, and
      satisfactory appearance in a year after transplantation. The follicular unit-like
      wigs may have prospective industrial products in clinical application.

PMID- 22363844
TI  - The pathogenesis of Candida infections in a human skin model: scanning electron
      microscope observations.
AB  - Cutaneous candidiasis is an opportunistic infection that arises, in most cases,
      from endogenous, saprophytic candidal blastospores that selectively colonize
      oral, gastrointestinal, vaginal, and cutaneous epithelium. Candida albicans has
      been regarded as the most common causative agent in human fungal infections.
      However, other Candida species have become a significant cause of infection.
      Scanning electron microscope (SEM) observations were used to analyze the
      capability of C. albicans, C. tropicalis, and C. parapsilosis to adhere to human
      skin model, used in this study, which was found to mimic the human skin in vivo.
      The skin sections were inoculated with low and high concentration of the yeasts
      and followed for 1 and 5 days; then they were viewed by SEM. The electron
      microscopy observations revealed that all three yeasts tested adhered to the skin
      but C. albicans covered the entire skin model to a higher extent than C.
      tropicalis or C. parapsilosis. Mucin-like material coated the blastoconidia
      mainly in C. albicans. All Candida species have shown characteristics resembling
      biofilm formation. The use of human skin sections for ex vivo evaluation of
      adherence of various yeasts may partially explain the predominance of C. albicans
      in cutaneous pathogenicity.

PMID- 22363845
TI  - Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic
      Alopecia: The Effects of Atopy on AGA.
AB  - Background. We examined the efficacy of a new regimen to treat AGA, with
      attention to male patients who are atopic. Objective. To assess the efficacy of a
      four-part regimen for the treatment of AGA in atopic and nonatopic patients. NuH
      Hair is a novel topical combination of finasteride, dutasteride, and minoxidil,
      which is blended in a hypoallergenic lotion. The other three components included
      Rogaine foam, Propecia, and ketoconazole shampoo. Methods. A prospective pilot
      study was conducted in 15 patients. All patients were assessed for the presence
      of atopy. Each patient served as their own control. All patients were treated
      specifically with NuH Hair and were given the option to add any of the other
      components of the protocol to their regimen. Photographs were taken of each
      patient's scalp at months 0, 1, 3, 6, and 9. Results. All 15 patients
      demonstrated significant growth of hair. In those patients who utilized all 4
      components, significant growth was achieved in as little as 30 days. In those
      patients who choose only to utilize NuH Hair, significant growth was demonstrated
      after 3 months. Conclusion. Aggressively treating AGA achieves significant and
      rapid growth of new hair. This is effective in atopic and nonatopic male
      patients.

PMID- 22363841
TI  - Molecular mechanisms of neonatal brain injury.
AB  - Fetal/neonatal brain injury is an important cause of neurological disability.
      Hypoxia-ischemia and excitotoxicity are considered important insults, and, in
      spite of their acute nature, brain injury develops over a protracted time period
      during the primary, secondary, and tertiary phases. The concept that most of the
      injury develops with a delay after the insult makes it possible to provide
      effective neuroprotective treatment after the insult. Indeed, hypothermia applied
      within 6 hours after birth in neonatal encephalopathy reduces neurological
      disability in clinical trials. In order to develop the next generation of
      treatment, we need to know more about the pathophysiological mechanism during the
      secondary and tertiary phases of injury. We review some of the critical molecular
      events related to mitochondrial dysfunction and apoptosis during the secondary
      phase and report some recent evidence that intervention may be feasible also days
      weeks after the insult.

PMID- 22363846
TI  - Prognostic factors in cutaneous squamous cell carcinoma: is patient delay in
      hospital visit a predictor of survival?
AB  - The patient's delay in the visit to a hospital seems to play an important role in
      prognosis in invasive cutaneous squamous cell carcinoma (SCC). This report
      explored prognostic factors of cutaneous SCC focusing on patient delay in
      hospital visit. Data of 117 Japanese patients who were treated for invasive
      cutaneous SCC in our facility between 2000 and 2010 were used for analysis. A
      multivariate Cox proportional-hazard modelling revealed that a pair of TNM stage
      (hazard ratio, 5.0; 95% CI, 1.8 to 13.9) and poorer histological differentiation
      (hazard ratio, 3.2; 95% CI, 0.93 to 10.3), and a pair of tumour size (hazard
      ratio, 1.02; 95% CI, 1.004 to 1.04) and rapid growth (hazard ratio, 8.25; 95% CI,
      1.29 to 52.7) were a prognostic factor whereas patient delay in hospital visit
      was not. However, patient delay in hospital visit was correlated with larger
      tumour size.

PMID- 22363847
TI  - Xanthoma disseminatum in a pair of blind, deaf male twins.
AB  - Xanthoma disseminatum (XD) is a rare normolipemic histiocytic disorder of non
      Langerhans cell origin characterized by erythematous to tan/brown papules in
      flexor surfaces. Considered a generally benign, chronic disease of unknown
      etiology, XD typically affects the skin, mucous membranes, and less commonly,
      other organs. To date, there has been no typical or consistent inheritance
      pattern described, nor has it ever been considered as a component of any known
      syndrome. We describe, for the first time, two cases of XD in a pair of blind and
      deaf twin brothers.

PMID- 22363848
TI  - Photodynamic therapy for Basal cell carcinoma in recessive dystrophic
      epidermolysis bullosa.
AB  - A 22-year-old male with recessive dystrophic epidermolysis bullosa with a large
      superficial and nodular basal cell carcinoma on his right forehead was treated
      with photodynamic therapy. The treatment was well tolerated, and the site healed
      well. Patients with epidermolysis bullosa are at increased risk of developing
      skin cancers, particularly squamous cell carcinomas. However, basal cell
      carcinomas are rare in recessive dystrophic epidermolysis bullosa. As patients
      with epidermolysis bullosa have recurrent blistering and poor wound healing,
      surgery may not be the optimal choice in treating skin cancers. We present this
      case to highlight that photodynamic therapy may be a helpful and safe technique
      in the treatment of superficial skin cancers in patients with epidermolysis
      bullosa, as an alternative to more radical methods.

PMID- 22363850
TI  - Atypical steatocystoma multiplex with calcification.
AB  - A 60-year-old male reported to us with an atypical case of giant steatocystoma
      multiplex in the scrotum with calcification. There was no family history of
      similar lesions. Yellowish, creamy material was expressed from a nodule during
      punch biopsy. The diagnosis was based on clinical as well as histological
      findings. Successful surgical excision was done to cure the case without any
      complications.

PMID- 22363849
TI  - Antimicrobial active clothes display no adverse effects on the ecological balance
      of the healthy human skin microflora.
AB  - The progressive public use of antimicrobial clothes has raised issues concerning
      skin health. A placebo-controlled side-to-side study was run with antimicrobial
      clothes versus fabrics of similar structure but minus the antimicrobial activity,
      to evaluate possible adverse effects on the healthy skin microflora. Sixty
      volunteers were enrolled. Each participant received a set of form-fitting T
      shirts constructed in 2 halves: an antibacterial half, displaying activities of 3
      5 log-step reductions due to silver-finishes or silver-loaded fibres and a
      nonantibacterial control side. The microflora of the scapular skin was analyzed
      weekly for opportunistic and pathogenic microorganisms over six weeks. The
      antibacterial halves did not disturb the microflora in number or composition,
      whereas a silver-containing deodorant displayed a short-term disturbance.
      Furthermore, parameters of skin morphology and function (TEWL, pH, moisture) did
      not show any significant shifts. In summary, antimicrobial clothes did not show
      adverse effects on the ecological balance of the healthy skin microflora.

PMID- 22363852
TI  - Use of surgical sponge with running sutures for securing full-thickness skin
      grafts.
AB  - One of the most common methods of skin defect repairing is the use of a skin
      graft. It is simple and reliable technique, although sometimes it is not totally
      successful due to hematoma and seroma formation between the skin graft and the
      recipient bed. Here in, we present a method to secure the skin grafts using a
      surgical sponge with two running sutures. This technique ensures high survival
      rate of the skin grafts, and in addition it is easy to be performed by the
      surgeon only.

PMID- 22363851
TI  - Prognostic variables and surgical management of foot melanoma: review of a 25
      year institutional experience.
AB  - Introduction. Cutaneous foot melanoma is rare, challenging to manage, and not
      adequately examined in the literature. This study evaluated the prognostic
      variables and surgical management of foot melanoma. Materials and Methods. Foot
      melanoma cases managed at an academic center from 1985 to 2010 were
      retrospectively reviewed. Results. 46 patients were identified with a broad range
      of demographic characteristics. Overall recurrence was 32.6%: 19% acral
      lentiginous, 57% nodular, 66% superficial spreading, 30% melanoma unspecified,
      50% severely atypical; 53% ulcerated, 23% nonulcerated; 29% on the dorsum of the
      foot, 17% heel, 60% ankle, 22% toe, 50% plantar; 0% <1 mm thick, 47% 1-4 mm, 33%
      >4 mm. 13 had positive nodes, 4 (31%) of whom recurred. Prognostic factors and
      recurrence did not correlate, and survival was 96% with a median followup of 91
      months. Conclusions. Aggressive management of foot melanoma may result in
      excellent long-term survival even following disease recurrence.

PMID- 22363854
TI  - Primary Cutaneous CD30-Positive Large T-Cell Lymphoma in an 80-Year-Old Man: A
      Case Report.
AB  - Primary cutaneous CD30-positive large cell lymphoma (CD30+ PCLCL) is a rare
      subtype of cutaneous T-cell lymphoma (CTCL) that can present in a variety of
      ways. We report a patient with a three-month history of an enlarging, exophytic
      mass with two smaller satellite lesions on the left forearm. Biopsy of the skin
      stained positive for CD30, and, after thorough systemic evaluation, a diagnosis
      of CD30+ PCLCL was made. When PCLCL is suspected, it is important to perform
      immunohistological studies for CD30 types and conduct a thorough workup to rule
      out systemic LCL. These measures will reduce the use of unnecessarily aggressive
      chemotherapy regimens for CD30+ PCLCL, an indolent disease with a favorable
      prognosis.

PMID- 22363853
TI  - Biologicals and fetal cell therapy for wound and scar management.
AB  - Few biopharmaceutical preparations developed from biologicals are available for
      tissue regeneration and scar management. When developing biological treatments
      with cellular therapy, selection of cell types and establishment of consistent
      cell banks are crucial steps in whole-cell bioprocessing. Various cell types have
      been used in treatment of wounds to reduce scar to date including autolog and
      allogenic skin cells, platelets, placenta, and amniotic extracts. Experience with
      fetal cells show that they may provide an interesting cell choice due to facility
      of outscaling and known properties for wound healing without scar. Differential
      gene profiling has helped to point to potential indicators of repair which
      include cell adhesion, extracellular matrix, cytokines, growth factors, and
      development. Safety has been evidenced in Phase I and II clinical fetal cell use
      for burn and wound treatments with different cell delivery systems. We present
      herein that fetal cells present technical and therapeutic advantages compared to
      other cell types for effective cell-based therapy for wound and scar management.

PMID- 22363856
TI  - A girl with cutaneous lesions, polyarthritis, and antinuclear antibodies
      positivity.
AB  - On October 1996, a 14-year-old girl was admitted to the hospital because
      cutaneous lesions, asthenia, and arthralgias. On examination, there was
      nonscarring hair thinning with a widened part over the frontal hairline,
      polymorphic papulosquamous rash on her face, neck, arms, and trunk, and livedo
      reticularis in her legs. Multiple aphtous ulcers were present on the buccal and
      nasal mucosa. There was polyarthritis involving the wrist, metacarpophalangeal
      joints, proximal interphalangeal joints, and metatarsophalangeal joints of both
      hands and feet. Skin biopsy of the face was compatible with subacute cutaneous
      lupus erythematosus. She started on prednisone 60 mg/d without improvement, and
      later hdroxhchloroquine (HCQ) 6 mg/kg/d was added for one year. Cutaneous lesions
      were almost healed, with just a hypopigmented macules left. Over the last 14
      years, she has not shown any cutaneous or systemic manifestations.

PMID- 22363855
TI  - Nevus senescence.
AB  - Melanomas and nevi share many of the same growth-promoting mutations. However,
      melanomas grow relentlessly while benign nevi eventually undergo growth arrest
      and stabilize. The difference in their long-term growth potential may be
      attributed to activation of cellular senescence pathways. The primary mediator of
      senescence in nevi appears to be p16. Redundant, secondary senescence systems are
      also present and include the p14-p53-p21 pathway, the IGFBP7 pathway, the FBXO31
      pathway, and the PI3K mediated stress induced endoplasmic reticulum unfolded
      protein response. It is evident that these senescence pathways result in an
      irreversible arrest in most instances; however, they can clearly be overcome in
      melanoma. Circumvention of these pathways is most frequently associated with gene
      deletion or transcriptional repression. Reactivation of senescence mechanisms
      could serve to inhibit melanoma tumor progression.

PMID- 22363857
TI  - Unusual presentation of a rare tumor of the dorsal surface of the foot.
AB  - Calcifying aponeurotic fibroma (CAF) was originally described by Keasbey in 1953
      as juvenile aponeurotic fibroma, most commonly occurring in the palms of the
      hands and soles of the feet in children and adolescents. It usually presents as a
      firm, painless mass without preceding trauma. We report a case of this rare
      condition with an unusual presentation in a 60-year-old woman affecting the
      dorsal surface of the foot. It is a relatively benign condition with a good
      prognosis following complete surgical excision. It may have a slightly increased
      incidence in males. The accurate diagnosis is based only on histology but it is
      essential to differentiate it from other sinister lesions such as fibrosarcoma
      that may lead to amputation.

PMID- 22363858
TI  - Tinea corporis gladiatorum presenting as a majocchi granuloma.
AB  - Background. Wrestlers are at increased risk of developing cutaneous infections,
      including fungal infections caused by dermatophytes. Erythematous lesions due to
      tinea infections can be mistakenly diagnosed as an inflammatory dermatitis and
      incorrectly treated with potent topical corticosteroid treatments which cause
      localized skin immunosuppression. This can eventuate in a Majocchi granuloma
      which then becomes refractory to topical antifungal therapy. To our knowledge,
      this is the first case of tinea corporis gladiatorum presenting as a Majocchi
      granuloma. Observations. A 20-year-old wrestler presented with a 4-year history
      of a large pruritic, scaly erythematous plaque with follicular papules, and
      pustules on his right forearm. The lesion had the clinical appearance of a
      Majocchi granuloma. He had been treated with potent topical corticosteroids and
      topical antifungal therapy. KOH and fungal culture of the lesion were negative.
      An erythematous scaly lesion in the scalp was cultured and grew Trichophyton
      tonsurans. Oral Terbinafine therapy was initiated and complete resolution of both
      lesions occurred within 6 weeks. Conclusion. The purpose of this report is to
      inform dermatologists that tinea corporis gladiatorum can present as a Majocchi
      granuloma and needs to be considered in the differential diagnosis of persistent
      skin lesions in wrestlers.

PMID- 22363859
TI  - Neoadjuvant use of photodynamic therapy in Basal cell and squamous cell
      carcinomas of the face.
AB  - Background. This preliminary study sought to determine the success of
      photodynamic therapy (PDT) in reducing lesion size in an effort to assess the
      potential application of this treatment approach in a neoadjuvant role.
      Objectives. To quantify the effects of PDT on lesion area (mm(2)) for basal cell
      and squamous cell carcinomas of the face. Results. Eighteen participants (10 BCC
      lesions and 8 SCC lesions of the face) were assessed. Four lesions (all from the
      BCC group) showed a complete response to PDT. Of the remaining 14 lesions, 85.7%
      (n = 12) showed reductions in lesion area, while two lesions showed increase in
      lesion area. Proportional reductions for the 12 lesions that did not demonstrate
      complete response or an increase in area following-PDT were found to range from
      13.2% to 85.1% (BCC) and 6.7% to 89.7% (SCC). Conclusions. PDT as a neoadjuvant
      treatment may provide a simple, efficient, and viable approach to reducing the
      area of malignant lesions of the face with the advantage of reduced cosmetic and
      aesthetic morbidities.

PMID- 22363860
TI  - Nevogenesis: a benign metastatic process?
AB  - It is generally accepted that cutaneous nevogenesis is a localized event that
      occurs exclusively in the dermis and/or epidermis. However, the discovery of
      nevocytes circulating in the peripheral blood suggests that other, more systemic,
      benign metastatic processes could also be involved. The theoretical role of
      lymphatic and hematogenous dissemination of loosely adherent, immature nevus
      progenitor cells in the development of nodal nevi and eruptive melanocytic nevi
      will be reviewed.

PMID- 22363861
TI  - Incontinentia pigmenti and bipolar aphthosis: an unusual combination.
AB  - Incontinentia pigmenti (IP) is an uncommon X-linked dominant multisystem
      disorder, lethal in the majority of affected males in utero and variably
      expressed in females. The cutaneous manifestations are diagnostic and classically
      occur in four stages: vesicular, verrucous, hyperpigmented, and atrophic. The
      skin lesions are typically spread along the lines of Blaschko, and they are
      usually present at birth. It may be variably accompanied by dental, ocular,
      neurologic, bones and joints, and development anomalies. The genes IP has been
      mapped to Xq28. Mutations in the NEMO/IKKgamma gene, located at Xq28, have been
      found to cause expression of the disease. Behcets disease is a multisystem
      disorder consisting of recurrent oral aphtae, genital ulcers, pustular skin
      eruption, and uveitis. Occasionally there are other articular, neurological,
      intestinal, or vascular abnormalities. This disease is rare in children. Here, we
      report a case of a 16-year-old female with the rare combination of incontinentia
      pigmenti and an aphthosis bipolar, and we discuss the probably relationship
      between these two diseases.

PMID- 22363862
TI  - Immunohistochemical Reactivity of the 14F7 Monoclonal Antibody Raised against N
      Glycolyl GM3 Ganglioside in Some Benign and Malignant Skin Neoplasms.
AB  - The evaluation of 14F7 Mab (anti-N-glycolyl GM3 ganglioside) immunorecognition in
      normal skin, cutaneous malignant melanoma (CMM), and in lymph node metastases
      (LNM) has been previously reported. In this work we extended the study to benign
      (BMN) and dysplastic (DMN) melanocytic nevi, basal (BCC), and squamous cell
      carcinoma (SCC). Immunohistochemical assays with 14F7 followed by a biotinylated
      link universal and streptavidin-AP in normal and pathological tissues were made.
      No reaction of 14F7 in normal skin (0/10) as well as a low reactivity in BMN
      (2/11) and DMN (1/7) was detected. A limited staining in BCC (2/13) and in SCC
      (4/8) was also evidenced, while 14F7 Mab were mostly reactive in CMM (28/28) and
      in LNM (6/7). These results suggest that 14F7 reactivity could be closely related
      with the more aggressive biological behavior of CMM and also support the use of
      NeuGcGM3 as target for both passive and active melanoma immunotherapy.

PMID- 22363863
TI  - Severe Hair Loss of the Scalp due to a Hair Dye Containing Para phenylenediamine.
AB  - We report the case of a 41-year-old female showing severe hair loss approximately
      90% after the use of a hair dye. These symptoms developed six days after the use
      of a hair dye containing PPD. A patch test showed a (++) reaction at 48 h to 1%
      PPD in petrolatum, whereas all metals and white petrolatum were negative. She was
      therefore diagnosed with contact dermatitis due to PPD, resulting in hair loss.
      The skin lesions gradually improved after starting treatment with the systemic
      corticosteroids. The possibility that allergic contact dermatitis from hair dyes
      may be responsible for telogen effluvium should always be considered in a patient
      with increased hair loss.

PMID- 22363865
TI  - The vitiligo in senegal.
AB  - The aim of our study was to determine the epidemiological and clinical aspects of
      vitiligo in the largest dermatology department of Senegal. A cross-sectional and
      descriptive study in a period of 5 months was performed covering all the vitiligo
      cases. Fifty patients were identified (26 women and 24 men). The mean age was
      26.5 years. A family history of vitiligo was found in 11 cases and a
      psychoaffective disturbance in 6 cases. The clinical forms distinguished were
      generalized vitiligo (n = 33), localized vitiligo (n = 16), vitiligo universalis
      (n = 4), and segmental vitiligo (n = 1). The Koebner phenomenon was found in 7
      cases. Associated diseases were atopic dermatitis (n = 2), contact dermatitis (n
      = 1), diabetes (n = 1), and Graves' disease (n = 1). The disgraceful character of
      Vitiligo was the predominance of generalized forms and the elective localization
      in sun-exposed areas. The family character, the psychoaffective disturbances, the
      Koebner phenomenon increased by the lifestyle and the itching dermatosis were the
      aggravating factors.

PMID- 22363866
TI  - Prevalence of Decreased Vitamin D Levels is High among Veterans with Diabetes
      and/or CKD.
AB  - Objective. Vitamin D deficiency is associated with a variety of skeletal and
      extraskeletal problems. The aim of this study was to evaluate the prevalence of
      vitamin D deficiency among veterans in sunny Louisiana. Methods. Using the VA
      computerized patient record system, we searched for all 25 (OH) Vitamin D and 1,
      25 (OH) vitamin D levels that were measured between 2007 and 2009. The
      information collected for each patient included age, body mass index, creatinine,
      history of diabetes and hypertension, and levels of vitamin D and PTH. We
      determined the number of individuals who were vitamin D insufficient and
      deficient. Results. Among 2990 studies evaluated, the mean concentration of 25
      (OH) D was 22.5 +/- 0.2 ng/mL, and that of 1, 25 (OH) vitamin D was 29.2 +/- 0.4
      ng/mL. Among them, only 695 subjects (23%) had normal values, while 889 (30%) had
      insufficiency, and 1405 (47%) had deficiency. Subjects with diabetes (1041) had
      significantly (P < 0.0001) lower levels (21 and 25 ng/mL) of both 25 (OH) and
      1,25 (OH) vitamin D compared to subjects without diabetes (23 and 32 ng/mL).
      Similarly, subjects with chronic kidney disease (1128) had much lower vitamin D
      levels than subjects without CKD. Among subjects with diabetes, those with
      chronic kidney disease (512) had much lower levels of both 25 (OH) and 1,25 (OH)
      vitamin D than with those with normal creatinine levels. Conclusions. We conclude
      that vitamin D insufficiency and deficiency is highly prevalent in veterans, more
      so among subjects with diabetes and/or CKD.

PMID- 22363864
TI  - Cell proliferation in cutaneous malignant melanoma: relationship with neoplastic
      progression.
AB  - The establishment of the diagnosis of cutaneous malignant melanoma (CMM) always
      calls for histopathological confirmation. Further to the recognition of the CMM
      aspects, immunohistochemistry is helpful, in particular, in determining the size
      of the replicative compartment and the activity in each of the cell cycle phases
      (G(1), S, G(2), M). The involvement of cancer stem cells and transient amplifier
      cells in CMM genesis is beyond doubt. The proliferation activity is indicative of
      the neoplastic progression and is often related to the clinical growth rate of
      the neoplasm. It allows to distinguish high-risk CMM commonly showing a high
      growth rate, from those CMMs of lower malignancy associated with a more limited
      growth rate. The recruitment and progression of CMM cells in the cell cycle of
      proliferation depend on mitogen-activated protein kinase (MAPK) pathway and
      result from a loss of control normally involving a series of key regulatory
      cyclins. In addition, the apoptotic pathways potentially counteracting any excess
      in proliferative activity are out of the dependency of specific regulatory
      molecular mechanisms. Key molecular components involved in the deregulation of
      the growth fraction, the cell cycle phases of proliferation, and apoptosis are
      presently described in CMM.

PMID- 22363867
TI  - Endocrine alterations are the main determinants of cardiac remodelling in
      restrictive anorexia nervosa.
AB  - Objective. Anorexia nervosa is a condition of reduced hemodynamic load,
      characterized by varying degrees of cardiac remodelling, only in part related to
      reduced body mass; the mechanism for such variability, as well as its clinical
      significance, remains unknown. Aim of the study was to assess the possible
      influence of a great number of clinical, biochemical, and endocrine factors on
      cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five
      female patients hospitalized for restrictive anorexia nervosa underwent extensive
      cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted
      and cardiac workload-matched left ventricular mass was significantly related to
      several endocrine parameters, blood pressure, and vasoreactivity. On multivariate
      analysis, IGF/GH ratio and systolic blood pressure were the only independent
      predictors of height-adjusted ventricular mass (adj-R(2) = 0.585; P = 0.001);
      when matching for cardiac workload, left ventricular mass was independently
      predicted only by GH and FT3 levels. All effects were independent of patient's
      weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most
      relevant determinants of left ventricular hypotrophy in anorectic patients,
      apparently independent of reduced hemodynamic load and BMI. In particular, IGF/GH
      ratio and FT3 seem to particularly affect left ventricular mass in this
      population.

PMID- 22363868
TI  - Results of the prolonged use of subcutaneous continuous infusion of
      hydrocortisone in a man with congenital adrenal hyperplasia.
AB  - This is a case report study of a young man with Congenital Adrenal Hyperplasia
      (CAH) who has been treated during 2 years by a subcutaneous continuous infusion
      hydrocortisone (SCIH) to optimize his treatment. Hydrocortisone was delivered via
      an insulin infusion device. We also studied the evolution of testicular adrenal
      rest tumors (TARTs) and the quality of life through SF36 survey. Four rates were
      determined, with a total of 47 mg per day. Biochemical parameters were normalized
      at 2 months. The SF36 questionnaire showed a progress of well-being. The weight
      decreased to 106 kg, that is, -5 kg (height: 1.71 m). Unfortunatly, there was no
      change of the TARTs. Two episodes of dermohypodermitis, with abscess at the
      infusion site, were observed. This case demonstrates the feasibility of prolonged
      SCIH therapy in patients with CAH, reporting positive effects on quality of life
      and on BMI.

PMID- 22363870
TI  - The GH/IGF-I Axis and Cognitive Changes across a 4-Year Period in Healthy Adults.
AB  - After the age of 40, the amount of growth hormone in humans decreases. The
      reduced activity of the GH-IGF axis may play a role in age-related cognitive
      impairments. In the present study, mood and cognition of 30 healthy subjects (7
      males, 23 females, aged 41-76 yr, mean age 60.9 +/- 9.0) were examined twice. At
      baseline, we determined fasting blood levels of GH and IGF-I. Mood and cognitive
      status were assessed at baseline and after, on the average, 3 years and 9 months
      of followup. Working memory performance decreased over the years in the low IGF
      group (P = .007), but not the high IGF-I group. Higher levels of GH were related
      with a better working memory at the second test (r = 0.42, P = .01) while higher
      levels of IGF-I tended to be related with a better working memory (r = 0.3, P =
      .06). The results suggest that higher serum levels of GH and IGF-I preserve the
      quality of working memory functions over the years.

PMID- 22363869
TI  - Periodic Limbic Movement Disorder during Sleep as Diabetes-Related Syndrome? A
      Polysomnographic Study.
AB  - Introduction. Periodic limb movements during sleep (PLMs) is common in the
      elderly. When quality-of-life drops due to sleep disturbances, we speak about
      periodic limb movement disorder during sleep (PLMD). Another similar disorder,
      restless legs syndrome (RLS), is considered to be related to diabetes; RLS and
      PLMDs are genetically related. Our aim was to detect PLMDs in a population of
      diabetic patients and identify them as possible hallmarks of these autonomic
      disorders. Material and Methods. We selected 41 type-2 diabetics with no sleep
      comorbidity, and compared them with 38 healthy matched volunteers. All
      participants underwent the Epworth Sleepiness Scale (ESS) and polysomnography
      (PSG). A periodic limb movement (PLM) index >5, that is, the higher number of
      PLMs/sleep hour for the entire night, was considered as abnormal. Results.
      Diabetics showed lower sleep efficiency than controls on the ESS, lower
      proportions of REM and non-REM sleep, and higher arousal and PLM indexes, as
      assessed through PSG. PLMDs were diagnosed in 13 of 41 diabetic patients (31%);
      the latter showed lower sleep efficiency, lower non-REM slow-wave sleep, and
      increased arousal and PLM indexes. Conclusion. The relationship between PLMs
      related sleep fragmentation and endocrine carbohydrate metabolism regulation
      might be casual or genetically determined. This deserves further investigations.

PMID- 22363871
TI  - Culture models for studying thyroid biology and disorders.
AB  - The thyroid is composed of thyroid follicles supported by extracellular matrix,
      capillary network, and stromal cell types such as fibroblasts. The follicles
      consist of thyrocytes and C cells. In this microenvironment, thyrocytes are
      highly integrated in their specific structural and functional polarization, but
      monolayer and floating cultures cannot allow thyrocytes to organize the follicles
      with such polarity. In contrast, three-dimensional (3-D) collagen gel culture
      enables thyrocytes to form 3-D follicles with normal polarity. However, these
      systems never reconstruct the follicles consisting of both thyrocytes and C
      cells. Thyroid tissue-organotypic culture retains 3-D follicles with both
      thyrocytes and C cells. To create more appropriate experimental models, we here
      characterize four culture systems above and then introduce the models for
      studying thyroid biology and disorders. Finally, we propose a new approach to the
      cell type-specific culture systems on the basis of in vivo microenvironments of
      various cell types.

PMID- 22363872
TI  - Ultrasound-guided fine-needle aspiration biopsy in unselected consecutive
      patients with thyroid nodules.
AB  - The objective was to analyze the results of UG-FNAB, performed in unselected
      consecutive patients with thyroid nodules. Methods. The UG-FNAB records were
      analyzed in this retrospective study. Indication for biopsy was the presence of
      at least one nodule detected by ultrasound. Results. 330 patients at mean age +/-
      SD 48.4 +/- 11.2 years; women/men = 12.8/1 were analyzed. From the total 596
      nodules found 546 (91.6%) were investigated with 1231 punctures (2.3 per nodule
      and 3.7 per patient). Benign solitary nodules had 42.7%, multinodular goiter
      (MNG) 44.8%, inconclusive 4.8%, and others 2.1% and malignant nodules 5.5% of the
      patients (6.6% of solitary and 5.1% of MNG patients). The risk for a separate
      nodule in MNG to be malignant was 2.7%. Conclusions. UG-FNAB is a safe and
      reliable diagnostic approach for thyroid nodules. It is the method of choice for
      hypo- and isoechoic not purely cystic solitary nodules, regardless of the nodule
      size. In MNG, its positive predictive value and diagnostic accuracy are lower.
      The final decision for regular US monitoring, UG-FNAB of the dominant nodule,
      multipuncture UG-FNAB or surgical exploration is one of complex appraisal. We
      consider UG-FNAB appropriate for most nodules in MNG, according to the above
      mentioned criteria.

PMID- 22363873
TI  - Decrease in TSH Receptor Autoantibodies during Antithyroid Treatment:
      Relationship with a Long Noncoding Heg RNA and Cdk1 mRNA in Mononuclear Cells.
AB  - We have previously shown that a long noncoding RNA transcript Heg is negatively
      correlated with TSH receptor autoantibodies (TRAb) in patients with untreated
      Graves' disease and with CD14 mRNA in treated patients and controls. Thus
      patients with high concentrations of Heg RNA have low levels of TRAb or CD14
      mRNA, respectively. Here we show that an additional factor, gene expression of
      Cdk1 in mononuclear cells, is positively related to concentrations of TRAb in
      patients with untreated Graves' disease. Cdk1 mRNA is very important for
      regulation of cell cycle activity. It is well known that TRAb decrease
      significantly during treatment with antithyroid drugs. This decrease during
      treatment cannot be explained by Heg RNA, which remains unchanged. Cdk1 mRNA
      decreased significantly during treatment to values below values obtained in
      normal subjects. Thus both Heg RNA and Cdk1 mRNA may influence the level of TSH
      receptor autoantibodies but by different mechanisms.

PMID- 22363874
TI  - Analysis of clinical outcome of patients with poorly differentiated thyroid
      carcinoma.
AB  - Background. We retrospectively analyzed whether poor differentiation is the
      independent prognostic factor for thyroid carcinoma or not. Methods. The subjects
      were 29 patients with PDTC who were treated between April 1996 and March 2006 to
      compare with those of well-differentiated papillary carcinoma patients (n = 227).
      Results. The relapse free (RFS), distant relapse-free survival and cause-specific
      survival, rates were significantly lower in patients with PDTC (P < .0001, P <
      .001, and P < .05). After classification into focal (<10%) and diffuse type (over
      10%) of PDTC, there were no significant differences in RFS and cause-specific
      survival due to component type or proportion of poorly differentiated component.
      On multivariate analysis, poor differentiation (P < .0005, RR = 4.456, 95% CI;
      1.953-10.167) and extrathyroidal infiltration (P < .05, RR = 2.898, 95% CI; 1.278
      6.572) showed a significant impact on DFS, and poor differentiation (P < .05, RR
      = 9.343, 1.314-66.453) and age (P < .005, RR = 1.306, 1.103-1.547) significantly
      impacted cause-specific survival. Conclusion. Poor differentiation was an
      independent factor for survival. Distant relapse was significantly more common
      among PDTC patients, and systemic therapy might be warranted.

PMID- 22363875
TI  - Factors associated with healthcare services utilization and pharmacological
      treatment in individuals with diabetes diagnosis: lessons from a nationwide
      program for diabetes mellitus detection in Brazil.
AB  - The Brazilian Nationwide Population Screening Program for Diabetes, conducted in
      2001, diagnosed 346,168 new cases. Although unexpected, approximately 65,000
      previously diabetic individuals participated. We describe their characteristics
      compared to new cases, based on data obtained by a follow-up study of a subsample
      of 4991 positively screened from a representative sample of 90,106 individuals.
      Two groups were analyzed regarding factors associated with adherence to
      treatment, healthcare services utilization, and compliance to pharmacological
      treatment: 497 with newly diagnosed diabetes and 257 individuals with previous
      diabetes diagnosis who were not under treatment at the screening program. For
      this group, healthcare service utilization was lower when compared with the new
      cases (OR = 0.06; 95% CI: 0.03-0.12). Diabetes status (OR = 0.23; 95% CI: 0.14
      0.37), a healthy behavior score (OR = 0.53, 95% CI: 0.34-0.83), and glucose
      levels at screening (altered, OR = 5.01; 95% CI: 2.38-10.6 and likely and very
      likely DM OR = 11.2; 95% CI: 6.85-18.4) were independently associated with
      pharmacological treatment.

PMID- 22363876
TI  - The effect of multidisciplinary lifestyle intervention on the pre- and
      postprandial plasma gut Peptide concentrations in children with obesity.
AB  - Objective. This study aims to evaluate the effect of a multidisciplinary
      treatment of obesity on plasma concentrations of several gut hormones in fasting
      condition and in response to a mixed meal in children. Methods. Complete data
      were available from 36 obese children (age 13.3 +/- 2.0 yr). At baseline and
      after the 3-month multidisciplinary treatment, fasting and postprandial blood
      samples were taken for glucose, insulin, ghrelin, peptide YY (PYY), and glucagon
      like peptide 1 (GLP-1). Results. BMI-SDS was significantly reduced by
      multidisciplinary treatment (from 4.2 +/- 0.7 to 4.0 +/- 0.9, P < .01). The
      intervention significantly increased the area under the curve (AUC) of ghrelin
      (from 92.3 +/- 18.3 to 97.9 +/- 18.2 pg/L, P < .01), but no significant changes
      were found for PYY or GLP-1 concentrations (in fasting or postprandial
      condition). The insulin resistance index (HOMA-IR) remained unchanged as well.
      Conclusion. Intensive multidisciplinary treatment induced moderate weight loss
      and increased ghrelin secretion, but serum PYY and GLP-1 concentrations and
      insulin sensitivity remained unchanged.

PMID- 22363877
TI  - Glycemic Profiles of Healthy Individuals with Low Fasting Plasma Glucose and
      HbA1c.
AB  - Scant data exists on glucose profile variability in healthy individuals. Twenty
      nine healthy subjects without diabetes (86% male; mean age, 38 years) were
      measured by a CGM system and under real-life conditions. The median percentage of
      time spent on the blood glucose >7.8 mmol/L for 24 hrs was greater than 10% in
      both NFG and IFG groups. When subjects were divided into either NFG group (i.e.,
      FPG levels of <5.6 mmol/L; n = 22) or IFG group (FPG levels of 5.6-6.9 mmol/L; n
      = 7), all CGM indicators investigated but GRADE scores, including glucose
      variability measures, monitoring excursions, hyperglycemia, hypoglycemia, and 24
      hour AUC, did not differ significantly between the two groups. GRADE score and
      its euglycemia% were significantly different between the two groups. Among
      various CGM indicators, GRADE score may be a sensitive indicator to discriminate
      glucose profiles between subjects with NFG and those with IFG.

PMID- 22363878
TI  - Growth hormone deficiency, short stature, and juvenile rheumatoid arthritis in a
      patient with autoimmune polyglandular syndrome type 1: case report and brief
      review of the literature.
AB  - Autoimmune polyglandular syndromes (APSs) include a cluster of autoimmune and
      nonautoimmune conditions which have been classified into subtypes. APSs type 1 is
      characterized by at least two of the following: chronic mucocutaneous
      candidiasis, chronic hypoparathyroidism, and autoimmune Addison's disease (AD).
      We report the chronological history of a female patient who presented with
      features most consistent with APS type 1, along with growth hormone deficiency
      and juvenile rheumatoid arthritis (JRA). In terms of her autoimmune diagnoses,
      she first presented with JRA at three years of age, then hypocalcemia and
      hypoparathyroidism at five years of age, type 1 diabetes (DM 1) at age eleven
      years, adrenal insufficiency at age fourteen years, recurrent mucocutaneous
      candidiasis as a teenager, growth hormone deficiency at age fourteen years
      leading to significant short stature, primary amenorrhoea, and hypogonadism, and
      finally alopecia at age twenty-six years. In addition to this, she has suffered
      other nonautoimmune medical problems including a Tetralogy of Fallot with a
      surgical repair at age six years. On review of the medical literature, we found
      no other previously reported case with this unique combination of medical
      problems.

PMID- 22363879
TI  - Expression of an Androgenic Gland-Specific Insulin-Like Peptide during the Course
      of Prawn Sexual and Morphotypic Differentiation.
AB  - The crustacean male-specific androgenic gland (AG) regulates sexual
      differentiation. In the prawn Macrobrachium rosenbergii, silencing an AG-specific
      insulin-like encoding transcript (Mr-IAG) inhibited the development of male
      sexual characters, suggesting that Mr-IAG is a key androgenic hormone. We used
      recombinant pro-Mr-IAG peptide to generate antibodies that recognized the peptide
      in AG cells and extracts, as verified by mass spectrometry. We revealed the
      temporal expression pattern of Mr-IAG and studied its relevance to the timetable
      of sex differentiation processes in juveniles and after puberty. Mr-IAG was
      expressed from as early as 20 days after metamorphosis, prior to the appearance
      of external male sexual characters. Mr-IAG expression was lower in the less
      reproductively active orange-clawed males than in both the dominant blue-clawed
      males and the actively sneak mating small males. These results suggest a role for
      Mr-IAG both in the timing of male sexual differentiation and in regulating
      reproductive strategies.

PMID- 22363880
TI  - Neurofunctional evaluation of young male offspring of rat dams with diabetes
      induced by streptozotocin.
AB  - Diabetes mellitus (DM) is a complex disease, being one of the most prevalent
      diseases worldwide. As a consequence, pregnancy-associated diabetes is
      increasingly common. Given the numerous studies about the influence of diabetes
      on offspring of diabetic rat dams, the neurological outcome is of outmost
      importance. This paper aimed at evaluating the neurofunctional performance of
      young male offspring of rat dams with diabetes induced by streptozotocin.
      Diabetes was induced in Wistar female rats by streptozotocin administration,
      while control groups received vehicle injection. At two-month survival period,
      male offspring from each group were randomized to the water maze Morris test, in
      order to assess their neurofunctional status. There was no significant difference
      between the groups as assessed by the Morris water maze test for spatial
      reference task. Our results point to the need of further investigation on the
      offspring neurofunctional performance.

PMID- 22363881
TI  - Abnormal glucose metabolism in Hispanic parents of children with acanthosis
      nigricans.
AB  - Objective. Assess the prevalence of abnormal glucose metabolism among Hispanic
      parents of children with acanthosis nigricans (AN). Methods. Hispanic families (n
      = 258) were evaluated for metabolic and anthropometric parameters including
      fasting glucose levels and AN status. Results. Mothers with AN+ children had IFG
      (17.3%) and 4% had glucose levels >=126 mg/dL (P = 0.028) compared to 7.1% and
      1.8% of mothers with AN- children, respectively. Mothers of AN+ children also had
      greater odds of having impaired fasting glucose levels (OR: 3.917, 95% CI: 1.475
      10.404; P < 0.004) but this was not the case for fathers (OR: 1.125, 95% CI:
      0.489-2.586; P = 0.781). Mothers of AN+ children were also more likely to be AN+
      (OR: 5.76, 95% CI: 2.98-11.13, P < 0.001). Screening discovered glucose levels
      >126 mg/dL in 9% of fathers with AN+ children. Conclusions. Hispanic mothers of
      AN+ children are at higher risk of carbohydrate metabolism abnormalities. AN in
      children can be a marker for prevention and delay programs aimed at identifying
      adults at risk for diabetes.

PMID- 22363882
TI  - Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in
      association with multiple factors of insulin resistance.
AB  - The present study was carried out to determine the effect of berberine on glucose
      homeostasis and several biomarkers associated with insulin sensitivity in male
      Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced
      diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ
      injection were divided into two groups. One group was used as the diabetic
      control and another treated by gavage feeding with 100 mg/kg/d of berberine in
      water containing 0.5% carboxymethyl cellulose. A group of rats without receiving
      STZ was used as the normal control. After 7 weeks, berberine supplementation
      moderately but significantly lowered fasting blood glucose levels and improved
      oral glucose tolerance. Berberine lowered plasma free fatty acids and C-reactive
      protein levels without affecting plasma insulin levels. Diabetic rats treated
      with berberine showed significantly lower plasma triacylglycerol and cholesterol
      levels. Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein
      tyrosine phosphatase-1B activities. In conclusion, berberine showed a dramatic
      effect of lowering blood cholesterol and triacylglycerols and improved moderately
      glucose homeostasis in STZ-induced diabetic rats in association with multiple
      factors related to insulin resistance.

PMID- 22363883
TI  - Cellular signal transduction pathways by leptin in colorectal cancer tissue:
      preliminary results.
AB  - The aim of the study was to analyse genes typing with the use of the
      oligonucleotide microarray technique (HG-U133A, Affymetrix) differentiating
      colorectal cancer tissues from tissues assessed histopathologically as healthy
      ones among a panel of 91 mRNA of genes encoding proteins involved in activation
      of cellular signal transduction pathways by leptin. Frozen tumor specimens from
      11 colon cancer patients in various stages of clinical progression of the disease
      in an I-IV stage scale according to the TNM staging were used in molecular tests.
      Among the genes participating in the cascade of signal transfer in cell activated
      by leptin, the following ones: AKT1, STAT3, MCL1 were qualified as
      differentiating stage I and II and VEGFC, CCNDI the encoding genes respectively
      as differentiating III and IV stage neoplasm. It is necessary to extend studies
      of analysis of cellular signal transduction pathways by leptin in colorectal
      cancer initiation and transformation processes.

PMID- 22363884
TI  - Glucagon stimulation testing in assessing for adult growth hormone deficiency:
      current status and future perspectives.
AB  - Growth hormone deficiency (GHD) is a well-recognized clinical syndrome in adults.
      However, due to the high frequency of normal serum IGF-I levels in hypopituitary
      adults with GHD, it is now widely accepted that despite normal levels of total
      IGF-I, adults clinically suspected with GHD within the appropriate clinical
      setting must undergo GH provocative testing to confirm its diagnosis. Although
      the insulin tolerance test (ITT) is labor intensive, contraindicated in the
      elderly and in adults with seizure disorders and ischemic heart disease, can be
      unpleasant for the patient, and is potentially hazardous, this test remains the
      gold standard test for the biochemical demonstration of GHD in adults. In
      contrast, with the unavailability of the GHRH and arginine test as the
      alternative test to the ITT in the United States since 2008, the glucagon
      stimulation test (GST) has since been increasingly used in the United States
      because of its availability, reproducibility, safety, lack of influence by gender
      and hypothalamic cause of GHD, and relatively few contraindications. In this
      paper, we discuss our recommendations in performing this test, the potential
      drawbacks in conducting and caveats in interpreting this test, and its future
      perspectives.

PMID- 22363885
TI  - Aggressive versus Low Dose Inhibition of the Renin-Angiotensin System for the
      Treatment of Microalbuminuria in Type 2 Diabetic Patients: A Pilot Study.
AB  - Objective. This study compares low dose versus aggressive inhibition of the renin
      angiotensin system (RAS) to treat microalbuminuria (MA). Methods. Patients with
      MA after a run-in period to control BP to <130/80 mm Hg with 10 mg benazepril
      plus other drugs and HbA1c levels to <8.0% were randomized to either continue 10
      mg benazepril (N = 12) or to take maximal doses of benazepril plus losartan in
      monthly stepwise increases to achieve normoalbuminuria (N = 11). Because MA is
      associated with CVD and inflammation, carotid intima medial thickness (CIMT) and
      endothelial function by peripheral arterial tonometry (PAT) as surrogate indices
      of atherosclerosis and highly sensitive C-reactive protein (hs-CRP) to assess
      inflammation were measured every six months. Results. BP, HbA1c levels, albumin :
      creatinine ratios, CIMT, PAT, and hs-CRP did not differ over a mean of 12 months
      between the two groups. Conclusions. Aggressive inhibition of the RAS is
      unnecessary to treat MA.

PMID- 22363886
TI  - Successful treatment of methimazole-induced severe aplastic anemia by granulocyte
      colony-stimulating factor, methylprednisolone, and cyclosporin.
AB  - A 52-year-old Japanese woman was examined because of general malaise, weight loss
      and a lump in her left breast. She was diagnosed with cancer of the left breast
      and Graves' disease, and was administered methimazole (MMI). A left mastectomy
      was performed for the breast cancer. She presented with a high fever and
      peripheral blood examination revealed a severe pancytopenia. She was diagnosed
      with severe aplastic anemia, and administered G-CSF, however, the treatment was
      unsuccessful. Thus, oral methyprednisolone and cyclosporin were added. There was
      a remarkable improvement in the peripheral blood count.

PMID- 22363887
TI  - Patient Acceptance, Ease of Use, and Preference for Norditropin NordiFlex with
      NordiFlex PenMate: Results from an Open-Label, User Survey of Everyday Use.
AB  - In this 12-week open-label, uncontrolled study, patients (n = 85; mean [SD] age
      11.2 [3.95] years) were trained to use an injection device with an automatic
      needle insertion accessory (NordiFlex/NordiFlex PenMate: Novo Nordisk A/S,
      Bagsvaerd, Denmark) for growth hormone (GH) injection. The opinions of patients
      and the physicians/nurses who trained patients on device were recorded by
      questionnaire. Most (88.4%) patients reported that the device was "very
      easy/easy" to use. The majority (82.4%) of patients were "very
      satisfied/satisfied" with the device and 64% wished to continue its use. Device
      training instructions were reported as "very easy/easy" by 96.1% of
      physicians/nurses, and 65.8% of participants could use the device after <=10
      minute training. In this study, NordiFlex PenMate was well accepted by patients
      and medical staff. Patients had a high opinion of the device and over half wished
      to continue its use. High patient acceptance may facilitate treatment adherence
      optimizing treatment outcomes.

PMID- 22363888
TI  - Prevalence of Subclinical Hypothyroidism among Patients with Acute Myocardial
      Infarction.
AB  - Introduction. Subclinical hypothyroidism (SCH) is defined as a serum thyroid
      stimulating hormone (TSH) level above the upper limit of normal despite normal
      levels of serum free thyroxine. There is growing evidence that SCH is associated
      with increased cardiovascular risk. We tried to investigate prevalence of SCH in
      acute myocardial infarction patients. Methods and Results. We evaluate free T3,
      free T4, and TSH levels of 604 patients (age 58.4) retrospectively, who have been
      admitted to the coronary intensive care unit between years 2004-2009 with the
      diagnosis of ST elevation (STEMI) or non-ST elevation acute myocardial infarction
      (NSTEMI). Mild subclinical hypothyroidism (TSH 4.5 to 9.9 mU/l) was present in 54
      (8.94%) participants and severe subclinical hypothyroidism (TSH 10.0 to 19.9
      mU/l) in 11 (1.82%). So 65 patients (10.76%) had TSH levels between 4.5 and 20.
      Conclusions. In conclusion, 65 patients (10.76%) had TSH levels between 4.5 and
      20 in our study, and it is a considerable amount. Large-scale studies are needed
      to clarify the effects of SCH on myocardial infarction both on etiologic and
      prognostic grounds.

PMID- 22363889
TI  - Multiple myeloma and diabetes.
AB  - Multiple myeloma is a malignant plasma cell disorder that accounts for
      approximately 10% of all hematologic cancers. It is characterized by accumulation
      of clonal plasma cells, predominantly in the bone marrow. The prevalence of type
      2 diabetes is increasing; therefore, it is expected that there will be an
      increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus.
      The treatment of multiple myeloma and diabetes mellitus is multifaceted. The
      coexistence of the two conditions in a patient forms a major challenge for
      physicians.

PMID- 22363890
TI  - Proteases in Plasma and Kidney of db/db Mice as Markers of Diabetes-Induced
      Nephropathy.
AB  - Db/db mice are overweight, dyslipidemic and develop diabetic complications,
      relevant for similar complications in human type 2 diabetes. We have used db/db
      and db/+ control mice to investigate alterations in proteinase expression and
      activity in circulation and kidneys by SDS-PAGE zymography, electron microscopy,
      immunohistochemistry, Western blotting, and in situ zymography. Plasma from db/db
      mice contained larger amounts of serine proteinases compared to db/+ mice.
      Kidneys from the db/db mice had a significantly larger glomerular surface area
      and somewhat thicker glomerular basement membranes compared to the db/+ mice.
      Furthermore, kidney extracts from db/+ mice contained metalloproteinases with
      M(r) of approximately 92000, compatible with MMP-9, not observed in db/db mice.
      These results indicate that higher levels of serine proteinases in plasma may
      serve as potential markers for kidney changes in db/db mice, whereas a decrease
      in MMP-9 in the kidney may be related to the glomerular changes.

PMID- 22363891
TI  - Testosterone, endothelial health, and erectile function.
AB  - Experimental and clinical studies have reported that testosterone has a critical
      role in the maintenance of homeostatic and morphologic corpus cavernosum
      components, essential for normal erectile physiology. Although the exact
      mechanisms mediated by testosterone in erectile function are still under
      investigation, recent research has suggested an important role in the regulation
      of endothelial cell (EC) biological functions. Besides stimulating the production
      of EC mediators, testosterone is also thought to promote the vasculogenic
      reendothelialization process, mediated by bone marrow-derived endothelial
      progenitor cells. Additionally, testosterone seems to modulate other erectile
      tissue components, including trabecular smooth muscle cells, nerve fibers, and
      tunica albuginea structure, all essential for the erectile process. This paper
      summarizes current data regarding testosterone-induced cellular and molecular
      mechanisms that regulate penile tissue components, focusing particularly on the
      role of testosterone in endothelial health and erectile function.

PMID- 22363892
TI  - Infertility in WNIN Obese Mutant Rats-Causes?
AB  - We are maintaining two obese mutant rat strains (WNIN/Ob and WNIN/GR-Ob) in our
      animal facility since 1997. These rat colonies are perpetuated by crossing
      heterozygous littermates, since the obese phenotypes of both genders turned out
      be infertile. The present study revealed the reasons for this infertility. The
      male obese rats, though appeared normal in terms of sperm count, sperm motility
      and testis histology, however found wanting in terms of libido. This appeared to
      be due to low circulating testosterone levels seen in these animals, which should
      also account for low testis and accessory gland weights seen in them. The females
      exhibited delayed puberty, in terms of days taken for opening of vagina,
      irregular oestrus cycles and had small ovaries and short and stumpy uterine
      horns. The FSH peak observed in control lean animals during oestrus stage of the
      sexual cycle and also the E2 peak of normal oestrus cycle was conspicuously
      absent in these animals. They also showed elevated levels of progesterone
      throughout the sexual cycle. Thus the infertility seen in these mutants could be
      attributed to their abnormal gonadosteroid levels and the resulting anatomical
      and physiological defects.

PMID- 22363893
TI  - Evaluation of Antihyperglycemic Activity of Citrus limetta Fruit Peel in
      Streptozotocin-Induced Diabetic Rats.
AB  - The present paper aims to evaluate antihyperglycemic activity of methanol extract
      of Citrus limetta fruit peel (MECL) in streptozotocin-induced (STZ; 65 mg/kg
      b.w.) diabetic rats. Three days after STZ induction, diabetic rats received MECL
      orally at 200 and 400 mg kg(-1) body weight daily for 15 days. Glibenclamide (0.5
      mg kg(-1) p. o.) was used as reference drug. Blood glucose levels were measured
      on 0th, 4th, 8th, and 15th days of study. Serum biochemical parameters namely,
      SGOT, SGPT and ALP were estimated. The TBARS and GSH levels of pancreas, kidney,
      and liver were determined. MECL significantly (P < 0.001) and dose dependently
      normalized blood glucose levels and serum biochemical parameters, decreased lipid
      peroxidation, and recovered GSH as compared to those of STZ control. The present
      paper infers that in STZ-induced diabetic Wistar rats, C. limetta fruit peel
      demonstrated a potential antihyperglycemic effect which may be attributed to its
      antioxidant property.

PMID- 22363894
TI  - Altered or Impaired Immune Response to Hepatitis B Vaccine in WNIN/GR-Ob Rat: An
      Obese Rat Model with Impaired Glucose Tolerance.
AB  - Obesity is shown to increase the incidence and severity of infectious diseases
      and individuals seem to exhibit poor antibody response to vaccination due to
      several inherent immune defects. With the increasing prevalence of impaired
      glucose tolerance (IGT) seen in obese individuals, the present study was aimed to
      investigate the basal immune response and immune response upon Hepatitis B
      vaccination (HBV) in an obese rat model WNIN/GR-Ob with impaired glucose
      tolerance (IGT). Decreased proportions of splenic CD4(+) T helper cells and
      CD3(+) T cells were observed in obese animals compared to lean animals. Upon HBV,
      obese animals showed reduced cell-mediated immunity and humoral immunity in terms
      of splenic lymphocyte proliferative response to Concanavalin A (Con A) and
      Hepatitis B surface antigen (HBsAg) and HBsAg-specific IgG response. Innate
      immunity as assessed in terms of Tumor Necrosis Factor alpha (TNF alpha) and
      Nitric oxide (NO) production by peritoneal macrophages upon HBV was low and
      unchanged, respectively, in obese animals. Thus long-term immunological memory is
      impaired or altered upon HBV.

PMID- 22363895
TI  - Association between Hypoadiponectinemia and Low Serum Concentrations of Calcium
      and Vitamin D in Women with Polycystic Ovary Syndrome.
AB  - Objective. To investigate the possible association of calcium and vitamin D
      deficiency with hypoadiponectinemia in women with PCOS. Subjects and Methods. In
      this case-control study, 103 PCOS cases and 103 controls included. The
      concentrations of calcium, 25-OH-vitamin D (25OHD), adiponectin, insulin,
      glucose, total cholesterol, HDL-cholesterol, triglyceride (TG), and androgens
      were measured in fasting blood samples. Results. Adiponectin (8.4 +/- 2.7 ng/mL
      versus 13.6 +/- 5 ng/mL in control group, P : 0.00), calcium (2 +/- 0.1 mmol/L
      versus 2.55 +/- 0.17 mmol/L in controls, P : 0.00), and 25-OH-Vit D (30 +/- 2.99
      nmol/L versus 43.7 +/- 5.2 nmol/L in control group, P : 0.00) levels were
      decreased in women with PCOS. Subjects with PCOS had higher concentrations of TG
      (1.4 +/- 0.77 mmol/L versus 1.18 +/- 0.75 mmol/L in control group, P : 0.019) and
      dehydroepiandrosterone sulfate (DHEA-S) (10.7 +/- 11 mmol/L versus 9.7 +/- 10.4,
      P : 0.02 in control group). There were significant correlations between
      adiponectin concentrations with calcium (r : 0.78, P : 0.00) and 25OHD levels (r
      : 0.82, P : 0.00). The association of hypoadiponectinemia and PCOS was not
      significant considering 25OHD as a confounding factor. Conclusion. The present
      findings indicate that the association of hypoadiponectinemia with PCOS is
      dependent on vitamin D. A possible beneficiary effect of vitamin D on the
      metabolic parameters in PCOS may be suggested.

PMID- 22363897
TI  - Malaria Knowledge, Concern, Land Management, and Protection Practices among Land
      Owners and/or Managers in Lowland versus Highland Ecuador.
AB  - To control malaria effectively, it is essential to understand the current
      knowledge, beliefs, concerns, land management practices, and mosquito bite
      protection methods in use by citizens. This study presents a comparative,
      quantitative, interview-based study of land owners and/or managers (n = 262) in
      the Ecuadorian lowlands (presently considered malarious) (n = 131) and highlands
      (potentially malarious in the future) (n = 131). Although respondents had a
      strong understanding of where the disease occurs in their own country and of the
      basic relationship among standing water, mosquitoes, and malaria, about half of
      respondents in potential risk areas denied the current possibility of malaria
      infection on their own property. As well, about half of respondents with
      potential anopheline larval habitat did not report its presence, likely due to a
      highly specific definition of suitable mosquito habitat. Most respondents who are
      considered at risk of malaria currently use at least one type of mosquito bite
      prevention, most commonly bed nets.

PMID- 22363898
TI  - Health Care Seeking Behavior among Caregivers of Sick Children Who Had Cerebral
      Malaria in Northwestern Nigeria.
AB  - Cerebral malaria is a significant cause of childhood morbidity in our region. The
      challenges of effective management include time and quality of treatment. The
      study appraised the health care seeking behavior of caregivers of sick children
      who developed cerebral malaria, in Zaria, northwestern Nigeria. Caregivers
      indentified were parents 29 (87.9%) and grandparents 4 (12.1%). Most of them were
      in the upper social classes. Health care options utilized before presentation at
      our facility were formal health facility 24 (72.7%), patent medicine seller 12
      (36.4%), home treatment 10 (30.3%), and herbal concoction 6 (18.2%) with majority
      24 (72.7%) using more than one option. Antimalarial therapy was instituted in 25
      (75.6%) of the cases. Mortality was significantly associated with the use of
      herbal concoction, treatment at a formal health facility and patent medicine
      seller, multiple convulsions, age less than 5 years, and noninstitution of
      antimalarial therapy before presentation. The study showed use of inappropriate
      health care options by caregivers and highlighted the need to pursue an awareness
      drive among caregivers on the use of health care options.

PMID- 22363899
TI  - Head and neck pathology: new developments in the diagnosis and pathogenesis of
      head and neck tumors.

PMID- 22363900
TI  - Endovascular embolization of carotid-cavernous fistulas: A pioneering experience
      in Peru.
AB  - BACKGROUND: Endovascular embolization represents the method of choice for the
      treatment of carotid-cavernous fistulas (CCFs). METHODS: We report our experience
      using the endovascular technique in 24 patients harboring 25 CCFs treated between
      October 1994 and April 2010, with an emphasis on the role of detachable balloons
      for the treatment of direct CCFs. RESULTS: Of the 16 patients who presented with
      direct CCFs (Barrow Type A CCFs) (age range, 7-62 years; mean age, 34.3 years),
      14 were caused by traumatic injury and 2 by a ruptured internal carotid artery
      (ICA) aneurysm. Eight patients (age range, 32-71 years; mean age, 46.5 years)
      presented with nine indirect CCFs (Barrow Types B, C, and D). The clinical follow
      up after endovascular treatment ranged from 2 to 108 months (mean, 35.2 months).
      In two cases (8%), the endovascular approach failed. Symptomatic complications
      related to the procedure occurred in three patients (12.5%): transient cranial
      nerve palsy in two patients and a permanent neurological deficit in one patient.
      Detachable balloons were used in 13 out of 16 (81.3%) direct CCFs and were
      associated with a cure rate of 92.3%. Overall, the angiographic cure rate was
      obtained in 22 out of 25 (88%) fistulas. Patients presenting with III nerve palsy
      improved gradually between 1 day and 6 months after treatment. Good clinical
      outcomes [modified Rankin scale (mRS) <= 2] were observed in 22 out of 24 (91.6%)
      patients at last follow-up. CONCLUSIONS: Endovascular treatment using detachable
      balloons still constitutes a safe and effective method to treat direct carotid
      cavernous fistulas.

PMID- 22363901
TI  - Induction of ER Stress-Mediated Apoptosis by alpha-Lipoic Acid in A549 Cell
      Lines.
AB  - BACKGROUND: alpha-Lipoic acid (alpha-LA) has been studied as an anticancer agent
      as well as a therapeutic agent for diabetes and obesity. We performed this study
      to evaluate the anticancer effects and mechanisms of alpha-LA in a lung cancer
      cell line, A549. MATERIALS AND METHODS: alpha-LA-induced apoptosis of A549 cells
      was detected by fluorescence-activated cell sorting analysis and a DNA
      fragmentation assay. Expression of apoptosis-related genes was analyzed by
      western blot and reverse transcription-polymerase chain reaction analyses.
      RESULTS: alpha-LA induced apoptosis and DNA fragmentation in A549 cells in a dose
      and time-dependent manner. alpha-LA increased caspase activity and the
      degradation of poly (ADP-ribose) polymerase. It induced expression of endoplasmic
      reticulum (ER) stress-related genes, such as glucose-regulated protein 78, C/EBP
      homologous protein, and the short form of X-box binding protein-1, and decreased
      expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis
      protein. Reactive oxygen species (ROS) production was induced by alpha-LA, and
      the antioxidant N-acetyl-L-cysteine decreased the alpha-LA-induced increase in
      expression of apoptosis and ER stress-related proteins. CONCLUSION: alpha-LA
      induced ER stress-mediated apoptosis in A549 cells via ROS. alpha-LA may
      therefore be clinically useful for treating lung cancer.

PMID- 22363902
TI  - Outcomes of Surgical Atrial Fibrillation Ablation: The Port Access Approach vs.
      Median Sternotomy.
AB  - BACKGROUND: The aim of this study is to evaluate the clinical and rhythm outcomes
      of atrial fibrillation (AF) ablation through a port access approach compared with
      sternotomy in patients with AF associated with mitral valve diseases. MATERIALS
      AND METHODS: From February 2006 through December 2009, 135 patients underwent
      biatrial AF ablation with a mitral operation via either a port-access approach
      (n=78, minimally invasive cardiac surgery [MICS] group) or a conventional
      sternotomy (n=57, sternotomy group). To adjust for the differences in the two
      groups' baseline characteristics, a propensity score analysis was performed.
      RESULTS: After adjustment, there were no significant differences in the two
      groups' baseline profiles. The cardiopulmonary bypass time was significantly
      longer (p=0.045) in the MICS group (176.0+/-49.5 minutes) than the sternotomy
      group (150.0+/-51.9 minutes). There were no significant differences (p=0.31) in
      the two groups' rate of reoperation for bleeding (MICS=6 vs. sternotomy= 2,
      p=0.47) or the requirement for permanent pacing (MICS=1 vs. sternotomy=3). The
      major event-free survival rates at two years were 87.4+/-8.1% in the MICS group
      and 89.6+/-5.8% in the sternotomy group (p=0.92). Freedom from late AF at 2 years
      was 86.8+/-6.2% in the MICS group and 85.0+/-6.9% in the sternotomy group
      (p=0.86). CONCLUSION: Both the port-access approach and sternotomy showed
      tolerable clinical outcomes following biatrial AF ablation with mitral valve
      surgery.

PMID- 22363896
TI  - Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the
      Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites.
AB  - Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of
      up to 200,000 infant deaths a year, through the effects of placental
      insufficiency leading to growth restriction and preterm delivery. Development of
      a vaccine is one strategy for control. Plasmodium falciparum-infected red blood
      cells accumulate in the placenta through specific binding of pregnancy-associated
      parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on
      the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by
      an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the
      potential to cause placental damage and compromise foetal growth. Multigravid
      women develop immunity towards VAR2CSA-expressing parasites in a gravidity
      dependent manner which prevents unfavourable pregnancy outcomes. Although current
      vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies
      artificially, this candidate may not provide protection during the first
      trimester and may only protect those women living in areas endemic for malaria.
      It is concluded that while insufficient information about placental-parasite
      interactions is presently available to produce an effective vaccine, incremental
      progress is being made towards achieving this goal.

PMID- 22363903
TI  - Continuous "over and over" suture for tricuspid ring annuloplasty.
AB  - BACKGROUND: A ring implantation in the tricuspid annulus requires many
      interrupted mattress sutures for correction of tricuspid regurgitation (TR). In
      this study, tricuspid ring annuloplasty was performed by 2-0 polypropylene
      continuous suture instead of multiple interrupted 2-0 polyester mattress sutures,
      and the efficacy of the method was evaluated. MATERIALS AND METHODS: This study
      included 20 patients who underwent tricuspid ring annuloplasty by continuous
      suture between May 2009 and July 2010. Four of the patients had an isolated TR,
      and the rest had a left-sided cardiac lesion. The concomitant tricuspid
      annuloplasty was performed after the left-sided heart surgery was completed and a
      Duran flexible ring prosthesis was used. RESULTS: There was no perioperative
      mortality or conduction problem. More than a moderate degree of TR was improved
      to less than a mild degree after the procedure. After the ring annuloplasty, the
      right atrial volume decreased from 123.7+/-69.2 mL to 74.5+/-37.4 mL, and the
      mean right atrial pressure was lowered from 18.7+/-12.2 mmHg to 8.9+/-5.5 mmHg.
      CONCLUSION: The continuous "over and over" suture may be a useful procedure for
      fixing the ring to the annulus and making an intentional annular placation in
      performing tricuspid ring annuloplasty.

PMID- 22363904
TI  - Surgical experience of ascending aorta and aortic valve replacement in patient
      with calcified aorta.
AB  - BACKGROUND: The conventional method of aortic cross-clamping is very difficult
      and increases the risk of cerebral infarct due to embolism of the calcified aorta
      in these patients. Accordingly, we analyzed our experience with 11 cases of
      ascending aorta and aortic valve replacement with hypothermic circulatory arrest.
      MATERIALS AND METHODS: From January 2002 to December 2009, 11 patients had
      ascending aorta and aortic valve replacement with hypothermic arrest at our
      hospital. We performed a retrospective study. RESULTS: There were 5 males and 6
      females, with a mean age of 68 years (range, 44 to 82 years). Eight patients had
      aortic stenosis, and 3 patients had aortic regurgitation. An aortic cannula was
      inserted into the right axillary artery in 3 patients and ascending aorta in 6
      patients. Two patients with aortic regurgitation had a remote access perfusion
      catheter inserted though the right femoral artery. The mean cardiopulmonary
      bypass time was 180 minutes (range, 110 to 306 minutes) and mean hypothermic
      circulatory arrest time was 30 minutes (range, 20 to 48 minutes). The mean rectal
      temperature during hypothermic circulatory arrest was 21C (range, 19C to 23C). No
      patient had any new onset of cerebral infarct or cardiovascular accident after
      surgery. There was no hospital mortality. Early complications occurred in 1
      patient who needed reoperation due to postoperative bleeding. Late complications
      occurred in 1 patient who underwent a Bentall operation due to prosthetic valve
      endocarditis. The mean follow-up duration was 32 months (range, 1 month to 8
      years) and 1 patient died suddenly due to unknown causes after 5 years.
      CONCLUSION: Patients with a calcified aorta can be safely treated with a
      technique based on aorta and aortic valve replacement under hypothermic
      circulatory arrest.

PMID- 22363905
TI  - Midterm Follow-up after Cryopreserved Homograft Replacement in the Aortic
      Position.
AB  - BACKGROUND: The long-term results of homografts used in systemic circulation are
      controversial. We assessed the long-term results of using a cryopreserved
      homograft for an aortic root or aorta and its branch replacement. MATERIALS AND
      METHODS: From June 1995 to January 2010, 23 patients (male:female=15:8, 45.4+/
      15.6 years) underwent a homograft replacement in the aortic position. The
      surgical techniques used were aortic root replacement in 15 patients and aortic
      graft interposition in 8 patients. Indications for the use of a homograft were
      systemic vasculitis (n=15) and complicated infection (n=8). The duration of
      clinical follow-up was 65+/-58 months. RESULTS: Early mortality occurred in 2
      patients (8.7%). Perioperative complications included atrial arrhythmia (n=3),
      acute renal failure (n=3), and low cardiac output syndrome (n=2). Late mortality
      occurred in 6 patients (26.1%). The overall survival rates at 5 and 10 years were
      66.3% and 59.6%, respectively. Six patients (28.6%) suffered from homograft
      related complications. CONCLUSION: Early results of homograft replacement in
      aortic position were favorable. However, close long-term follow-up is required
      due to the high rate of homograft-related events.

PMID- 22363906
TI  - Comparing 18F-Fluorodeoxyglucose Positron Emission Tomography and Video-assisted
      Thoracoscopic Surgery in the Evaluation of Small Pulmonary Nodules in Patients
      with a History of Malignancy.
AB  - BACKGROUND: The aims of the study were to determine the accuracy of
      fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting pulmonary
      metastasis through video-assisted thoracoscopic surgery (VATS), a technique that
      allows the excisional biopsy of small pulmonary nodules in patients with known
      malignancies. MATERIALS AND METHODS: Between October 2007 and April 2010, 28
      patients with known malignancies and small pulmonary nodules underwent VATS
      excisional biopsies. All patients were in follow-up for a previously treated
      malignancy. The malignancies included the following: colorectum (9), breast (6),
      head and neck (5), stomach (3), lymph (1), ovary (1), uterus (1), bladder (1),
      and liver (1). RESULTS: There were 16 men and 12 women whose mean age was 56.7
      years old (range, 38 to 77 years). The sizes of the mean nodules removed were
      11.3 mm (range, 7 to 21 mm). Diagnoses included metastatic (11),
      bronchioloalveolar carcinoma (1), primary adenocarcinoma (1), pulmonary
      tuberculosis (6), fibrosis (5), organizing pneumonia (3), lymphoid hyperplasia
      (1). Among these lesions, 46.4% were malignant. CONCLUSION: True positive FDG-PET
      was 39.2%. FDG-PET is not a sensitive test in the evaluation of patients with a
      history of an extrathoracic malignancy and newly diagnosed small pulmonary
      nodules. VATS excision allows the early diagnosis of small pulmonary nodules,
      with low morbidity, in patients with known malignancies.

PMID- 22363907
TI  - Surgical outcomes in small cell lung cancer.
AB  - BACKGROUND: The experience of a single-institution regarding surgery for small
      cell lung cancer (SCLC) was reviewed to evaluate the surgical outcomes and
      prognoses. MATERIALS AND METHODS: From July 1990 to December 2009, thirty-four
      patients (28 male) underwent major pulmonary resection and lymph node dissection
      for SCLC. Lobectomy was performed in 24 patients, pneumonectomy in eight,
      bilobectomy in one, and segmentectomy in one. Surgical complications, mortality,
      the disease-free survival (DFS) rate, and the overall survival rate were analyzed
      retrospectively. RESULTS: The median follow-up period was 26 months (range, 4 to
      241 months), and there was one surgical mortality (2.9%). Six patients (17.6%)
      experienced recurrence, all of which were systemic. Eight patients died during
      follow-up; four died of disease progression and the other four died of pneumonia
      or of another non-cancerous cause. The three-year DFS rate was 79.2+/-2.6% and
      the overall survival rate was 66.4+/-10.5%. Recurrence or death was significantly
      prevalent in the patients with lymph node metastasis (p=0.001) as well as in
      those who did not undergo adjuvant chemotherapy (p=0.008). The three-year
      survival rate was significantly greater in the patients with pathologic stage
      I/II cancer than in those with stage III cancer (84% vs. 13%, p=0.001).
      CONCLUSION: Major pulmonary resection for small cell lung cancer is feasible in
      selected patients. Patients with pathologic stage I or II disease showed an
      excellent survival rate after surgery and adjuvant treatment. Prospective
      randomized studies will be needed to define the role of surgery in early-stage
      small cell lung cancer.

PMID- 22363908
TI  - Postinfarct ventricular septal defect after coronary covered stent implantation.
AB  - We report a case of a postinfarction ventricular septal defect caused by an acute
      recurrent occlusion after the implantation of a covered stent, which was
      performed as a rescue procedure for the ruptured left anterior descending artery
      during a percutaneous coronary intervention. Although the emergent implantation
      of a covered stent for the ruptured coronary arteries such as the left main
      coronary artery or the origins of the left anterior descending artery can be
      performed during a percutaneous coronary intervention, and a coronary bypass
      surgery should be considered in order to decrease the risk of complete occlusion,
      thus providing a superior long term patency.

PMID- 22363909
TI  - Coronary-bronchial artery fistula manifested by hemoptysis and myocardial
      ischemia in a patient with bronchiectasis.
AB  - A coronary-bronchial artery fistula is a very rare congenital anomaly of the
      coronary artery whose etiology and pathogenesis have not yet been clarified. Most
      patients with coronary-bronchial fistulas are asymptomatic; however, some
      patients present with congestive heart failure, infective endocarditis,
      myocardial ischemia induced by a coronary steal phenomenon, or rupture of an
      aneurysmal fistula. Furthermore, patients with a coronary-bronchial artery
      fistula rarely manifest life-threatening hemoptysis due to the associated
      bronchiectasis. We report herein the case of a patient with a coronary-bronchial
      artery fistula who had bronchiectasis and a history of massive hemoptysis and
      myocardial ischemia.

PMID- 22363910
TI  - Total gastrectomy in gastric conduit cancer.
AB  - We report a very rare case of surgery on gastric conduit cancer. A 67-year-old
      male patient underwent esophagectomy and intrathoracic esophagogastrostomy for
      squamous cell carcinoma of the lower thoracic esophagus 27 months ago. Upon
      follow-up, a gastric carcinoma at the intra-abdominal part of the gastric conduit
      was found on an esophagogastroduodenoscopy. We performed total gastrectomy and
      esophagocolonojejunostomy in the manner of Roux-en-Y anastomosis. The
      postoperative course was not eventful and an esophagogram on the 10th
      postoperative day showed no leakage or stenosis of the passage. The patient was
      discharged on the 17th day with no complications.

PMID- 22363911
TI  - A surgically treated case of chronic necrotizing aspergillosis with pleural
      invasion.
AB  - Aspergillus is a ubiquitous fungus and can cause many levels of disease severity.
      Chronic necrotizing aspergillosis is a rare disease and few cases have been
      reported in Korea. We experienced a case of pleural aspergillosis that was
      treated successfully with medical and surgical interventions. The 52-year-old man
      who was diagnosed with chronic necrotizing pulmonary aspergillosis underwent
      surgical treatment including a lobectomy, decortication, and myoplasty. The
      patient was also medically treated with amphotericin B followed by voriconazole.
      Pleural irrigation with amphotericin B was also performed. A multi-dimensional
      approach should be considered for treating chronic necrotizing pulmonary
      aspergillosis.

PMID- 22363912
TI  - Large cell neuroendocrine carcinoma of the thymus: a two-case report.
AB  - A large cell neuroendocrine carcinoma (LCNEC) of the thymus is a very rare
      malignant tumor that has a very poor prognosis. The detailed clinical features of
      LCNEC are still unknown, including the long term prognoses and the definitive
      modalities of the treatment for LCNEC of the thymus. We are reporting 2 cases of
      an enlarged LCNEC of the thymus, both of which were diagnosed and treated by
      surgical resection followed by postoperative adjuvant chemoradiation therapy.
      Although recurrences and metastases of the LCNEC were noticed 1 and 4 years
      postoperatively for each case, aggressive surgical resection and adjuvant
      chemoradiation therapy may be helpful for a patient's long term survival.

PMID- 22363913
TI  - Myxoinflammatory fibroblastic sarcoma in the chest wall.
AB  - Myxoinflammatory fibroblastic sarcoma (MIFS) is a recently defined rare tumor. It
      is mainly found in the upper and lower extremities of adults. Due to its high
      local recurrence rate and low metastatic rate, it is classified as a low grade
      malignancy. Accurate diagnosis and early, wide excision are important for
      prognosis. Herein, we report a case of MIFS in a 35-year-old male patient that
      presented in an unusual location, the left chest wall. To our knowledge, this is
      the first reported case of MIFS in Korea and the second case to be reported
      within the global scientific literature involving the chest wall.

PMID- 22363914
TI  - Duodenal perforation caused by an inferior vena cava filter.
AB  - The inferior vena cava (IVC) filter is known as an effective and safe method for
      preventing fatal pulmonary thromboembolism in patients with deep vein thrombosis.
      Usually, the remaining IVC filters are asymptomatic and do not cause clinical
      problems. We report a case of duodenal perforation caused by a remaining IVC
      filter.

PMID- 22363915
TI  - Improving patients' adherence to physical activity in diabetes mellitus: a
      review.
AB  - Regular physical activity (PA) is a key element in the prevention and management
      of type 2 diabetes mellitus (T2DM). Participation in regular PA improves blood
      glucose control and can prevent or delay T2DM and its complications, along with
      positively affecting lipids, blood pressure, cardiovascular events, mortality,
      and quality of life. However, most people with T2DM are not active and show poor
      adherence. This paper reviews the possible barriers to PA and strategies to
      improve the adherence to PA. Based on the currently available literature, it is
      concluded that self-efficacy and social support from family, friends, and health
      care providers play the important role in adoption and maintenance of regular PA.
      Here we also highlight some new modern and innovative interventions that
      facilitate exercise participation and improve the adherence.

PMID- 22363916
TI  - Diabetic peripheral neuropathy in type 2 diabetes mellitus in Korea.
AB  - Diabetic peripheral neuropathy (DPN), a common and troublesome complication in
      patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of
      diabetic foot ulcer and lower limb amputation. These situations can negatively
      impact the quality of life of affected individuals. Despite its high prevalence
      and clinical importance, most diabetes mellitus patients not only do not
      recognize the presence of diabetic neuropathy, but also do not report their
      symptoms to physicians or other health care providers. Therefore, DPN is usually
      under diagnosed and undertreated. For early detection and appropriate
      intervention for DPN, a careful history, physical with neurologic examination,
      and prompt treatment are needed in T2DM patients.

PMID- 22363917
TI  - Anti-Obesity Drugs: A Review about Their Effects and Safety.
AB  - The current recommendations for the treatment of obese people include increased
      physical activity and reduced calories intake. When the behavioral approach is
      not sufficient, a pharmacologic treatment is recommended. In past years, numerous
      drugs have been approved for the treatment of obesity; however, most of them have
      been withdrawn from the market because of their adverse effects. In fact,
      amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an
      increased risk of psychiatric disorders and non-fatal myocardial infarction or
      stroke. Even if orlistat is not as effective as other drugs in reducing body
      weight, orlistat is presently the only available choice for the treatment of
      obesity because of its safety for cardiovascular events and positive effects on
      diabetic control. Hopefully, more effective and better tolerated anti-obesity
      drugs will be developed through an improved understanding of the multiple
      mechanisms and complex physiological systems targeting appetite.

PMID- 22363918
TI  - Fibroblast growth factor 21: a novel metabolic regulator.

PMID- 22363919
TI  - Various oscillation patterns of serum fibroblast growth factor 21 concentrations
      in healthy volunteers.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF21) was originally identified as a
      paroxysm proliferator activated receptor-alpha target gene product and is a
      hormone involved in metabolic regulation. The purpose of this study was to
      investigate the diurnal variation of serum FGF21 concentration in obese and non
      obese healthy volunteers. METHODS: Blood samples were collected from five non
      obese (body mass index [BMI] <=23 kg/m(2)) and five obese (BMI >=25 kg/m(2))
      healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21
      concentrations were determined by radioimmunoassay. Anthropometric parameters,
      glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also
      measured. RESULTS: The serum FGF21 concentrations displayed various individual
      oscillation patterns. The oscillation frequency ranged between 6 and 12 times per
      day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0
      hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm.
      However, the oscillation frequency had a diurnal variation and was lower during
      the light-off period than during the light-on period (2.4 vs. 7.3 times,
      P<0.001). There was no difference in the total frequency or duration of
      oscillations between non-obese and obese subjects, but obese individuals had
      increased numbers of larger oscillations (amplitude >=0.19 ng/mL). CONCLUSION:
      Various oscillation patterns in serum FGF21 concentration were observed, and
      reduced oscillation frequencies were seen during sleep. The oscillation patterns
      of serum FGF21 concentration suggest that FGF21 may be secreted into systemic
      circulation in a pulsatile manner. Obesity appeared to affect the amplitude of
      oscillations of serum FGF21.

PMID- 22363920
TI  - Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community.
AB  - BACKGROUND: Recently, the measurement of glycated hemoglobin (HbA1c) was
      recommended as an alternative to fasting plasma glucose or oral glucose tolerance
      tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c
      levels for diabetes mellitus screening in a Korean rural population. METHODS: We
      analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and
      generated a receiver operating characteristic curve to determine an appropriate
      HbA1c cutoff value for diabetes. RESULTS: The mean age of the subjects was 56.3+/
      8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral
      glucose tolerance tests were 97.5+/-25.6 and 138.3+/-67.1 mg/dL, respectively.
      The mean HbA1c level of the subjects was 5.7+/-0.9%. There were 8,809 non-DM
      patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between
      HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose
      levels after oral glucose tolerance tests was found in a scatter plot of the
      data. Using Youden's index, the proper cutoff level of HbA1c for diabetes
      mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%). CONCLUSION:
      Our results suggest that the optimal HbA1c level for DM screening is 5.95%.

PMID- 22363921
TI  - Prevalence of Dyslipidemia among Korean Adults: Korea National Health and
      Nutrition Survey 1998-2005.
AB  - BACKGROUND: Dyslipidemia is a disorder of lipid metabolism, including elevated
      total cholesterol, elevated triglyceride, elevated low density lipoprotein
      cholesterol (LDL-C), and decreased high density lipoprotein cholesterol (HDL-C).
      The objective of this study was to investigate recent changes in the prevalence
      of dyslipidemia and also the rates of awareness, treatment, and control of
      dyslipidemia among Korean adults. METHODS: Dyslipidemia is defined according to
      the National Cholesterol Education Program-Adult Treatment Panel III as total
      cholesterol >=240 mg/dL, LDL-C >=160 mg/dL, HDL-C <40 mg/dL, and triglyceride
      >=200 mg/dL. The prevalence of dyslipidemia was estimated for adults aged >=20
      years using the Korea National Health and Nutrition Survey (KNHANES) in 1998
      (n=6,923), 2001 (n=4,882), and 2005 (n=5,323). Rates of awareness, treatment and
      control of dyslipidemia were calculated for adults aged >=30 years using the
      KNHANES in 2005 (n=4,654). RESULTS: The prevalence of dyslipidemia (aged >=20
      years) increased from 32.4% in 1998 to 42.6% in 2001 and 44.1% in 2005. Compared
      with the KNHANES in 1998, the prevalence of dyslipidemia was 47% (95% confidence
      interval [CI], 35% to 59%) higher in 2001 and 61% (95% CI, 49% to 75%) higher in
      2005. In 2005, only 9.5% of people with dyslipidemia were aware of the disease,
      5.2% used lipid-lowering medication, and 33.2% of patients with treatment reached
      treatment goals. CONCLUSION: The prevalence of dyslipidemia in Korea gradually
      increased between 1998 and 2005. These findings suggest that more intense efforts
      for the prevention and treatment of dyslipidemia may lead to further improvement
      in the management of dyslipidemia.

PMID- 22363922
TI  - The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean
      Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B.
AB  - BACKGROUND: Apolipoprotein A-II (apoA-II) is the second-most abundant
      apolipoprotein in human high-density lipoprotein and its role in cardio metabolic
      risk is not entirely clear. It has been suggested to have poor anti-atherogenic
      or even pro-atherogenic properties, but there are few studies on the possible
      role of apoA-II in Asian populations. The aim of this study is to evaluate the
      role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I
      (apoA-I) and apolipoprotein B (apoB) in Korean adults. METHODS: We analyzed data
      from 244 adults who visited the Center for Health Promotion in Pusan National
      University Yangsan Hospital for routine health examinations. RESULTS: The mean
      apoB level was significantly higher, and the mean apoA-I level was significantly
      lower, in MetS; however, there was no significant difference in apoA-II levels
      (30.5+/-4.6 mg/dL vs. 31.2+/-4.6 mg/dL, P=0.261). ApoA-II levels were more
      positively correlated with apoA-I levels than apoB levels. ApoA-II levels were
      less negatively correlated with homocysteine and high sensitivity C-reactive
      protein levels than apoA-I levels. The differences in MetS prevalence from the
      lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and
      6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared
      with the lowest quartile also was not significantly different (odds ratio, 0.96;
      95% confidence interval, 0.95 to 1.04; P=0.956). CONCLUSION: Compared with apoA-I
      (negative association with MetS) and apoB (positive association with MetS)
      levels, apoA-II levels did not show any association with MetS in this study
      involving Korean adults. However, apoA-II may have both anti-atherogenic and pro
      atherogenic properties.

PMID- 22363923
TI  - Clinical significance of the presence of autonomic and vestibular dysfunction in
      diabetic patients with peripheral neuropathy.
AB  - BACKGROUND: We investigated the prevalence of diabetic autonomic neuropathy (DAN)
      and vestibular dysfunction (VD) in diabetic patients with peripheral neuropathy.
      METHODS: Thirty-five diabetic patients with peripheral neuropathy were enrolled
      from August 2008 to July 2009. All subjects underwent autonomic function tests.
      Nineteen of the patients (54.3%) underwent videonystagmography. RESULTS: Diabetic
      autonomic neuropathy was observed in 28 patients (80%). A mild degree of
      autonomic failure was observed in 18 patients (64.3%), and a moderate degree of
      autonomic failure was observed in ten patients (35.7%). Factors related to DAN
      included diabetic nephropathy (P=0.032), degree of chronic kidney disease
      (P=0.003), and duration of diabetes (P=0.044). Vestibular dysfunction was
      observed in 11 of 19 patients (57.9%). There was no significant association
      between DAN and VD. CONCLUSION: Diabetic autonomic neuropathy was observed in 28
      diabetic patients (80%) with peripheral neuropathy. Vestibular dysfunction was
      observed in nearly 60% of diabetic patients with peripheral neuropathy who
      complained of dizziness but showed no significant association with DAN. Diabetic
      patients who complained of dizziness need to examine both autonomic function and
      vestibular function.

PMID- 22363924
TI  - Prevalence and correlates of disordered sleep in southeast asian indians with
      type 2 diabetes.
AB  - BACKGROUND: Sleep disturbances are common in individuals with diabetes. Patients
      with diabetes have higher rates of insomnia, excessive daytime sleepiness and
      increased incidence of restless leg syndrome. The purpose of our study was to
      investigate the prevalence and determine the predictors of sleep dysfunction in
      patients with type 2 diabetes in a southeast Asian Indian population. METHODS: We
      enrolled 120 patients with type 2 diabetes who attended an endocrinology clinic
      in a tertiary-care hospital. After we collected their demographic data, we
      recorded their anthropometric measurements. Fasting, postprandial blood glucose
      values and glycosylated hemoglobin (HbA1c) values were then obtained. Quality of
      sleep was evaluated in all the patients through the Pittsburgh Sleep Quality
      Index (PSQI), which is a questionnaire that assesses sleep quality and
      disturbances over a monthlong period. A Global Sleep Quality score >=5
      discriminates between good and poor sleepers. RESULTS: The mean global PSQI score
      was 7.08 (standard deviation, 3.89), which suggested poor sleep quality in this
      population. Sixty-nine percent of patients had a global PSQI score >=5,
      indicating that they were "poor sleepers." The global PSQI score positively
      correlated with the duration of diabetes and was also independent of other
      variables such as age, gender, body mass index, HbA1c, or medications.
      CONCLUSION: We found a high prevalence of sleep dysfunction in patients with type
      2 diabetes. We also found a significant correlation between duration of diabetes
      and quality of sleep, independent of other variables. It is important for
      physicians to address the quality and duration of sleep in patients with type 2
      diabetes.

PMID- 22363925
TI  - Response: the prevalence of peripheral arterial disease in korean patients with
      type 2 diabetes mellitus attending a university hospital (diabetes metab j
      2011;35:543-50).

PMID- 22363926
TI  - Letter: higher glycated hemoglobin level is associated with increased risk of
      ischemic stroke in non-diabetic korean male adults (diabetes metab j 2011;35:551
      7).

PMID- 22363927
TI  - Response: higher glycated hemoglobin level is associated with increased risk for
      ischemic stroke in non-diabetic korean male adults (diabetes metab j 2011;35:551
      7).

PMID- 22363928
TI  - Direct mass spectrometric detection of trace explosives in soil samples.
AB  - The detection of explosives in soil is of great significance in public security
      programmes and environmental science. In the present work, a ppb-level method was
      established to directly detect the semi-volatile explosives, RDX and TNT, present
      in complex soil samples. The method used thermal sampling technique and a direct
      current atmospheric pressure glow discharge source mounted with a brass cylinder
      electrode (9 mm * 4.6 mm i.d./5.6 mm o.d.) to face the samples, requiring no
      sample pretreatment steps such as soil extraction (about ten hours). It was
      characterized by the merits of easy operation, high sensitivity and fast speed,
      and has been validated by real soil samples from various locations around a
      factory or firecracker releasing fields. It took only 5 min per sample, with the
      limit of detection down to 0.5 ppb (S/N = 3) trinitrohexahydro-1,3,5-triazine in
      soils heated at 170  degrees C. It is also extendable to the analysis of other
      volatile analytes.

PMID- 22363929
TI  - Two-peak approximation in kinetic capillary electrophoresis.
AB  - Kinetic capillary electrophoresis (KCE) constitutes a toolset of homogeneous
      kinetic affinity methods for measuring rate constants of formation (k(+)) and
      dissociation (k(-)) of non-covalent biomolecular complexes, C, formed from two
      binding partners, A and B. A parameter-based approach of extracting k(+) and k(-)
      from KCE electropherograms relies on a small number of experimental parameters
      found from the electropherograms and used in explicit expressions for k(+) and k(
      ) derived from approximate solutions to mass transfer equations. Deriving the
      explicit expressions for k(+) and k(-) is challenging but it is justified as the
      parameter-based approach is the simplest way of finding k(+) and k(-) from KCE
      electropherograms. Here, we introduce a unique approximate analytical solution of
      mass transfer equations in KCE termed a "two-peak approximation" and a
      corresponding parameter-based method for finding k(+) and k(-). The two-peak
      approximation is applicable to any KCE method in which: (i) A* binds B to form C*
      (the asterisk denotes a detectable label on A), (ii) two peaks can be identified
      in a KCE electropherogram and (iii) the concentration of B remains constant. The
      last condition holds if B is present in access to A* and C* throughout the
      capillary. In the two-peak approximation, the labeling of A serves only for
      detection of A and C and, therefore, is not required if A (and thus C) can be
      observed with a label-free detection technique. We studied the proposed two-peak
      approximation, in particular, its accuracy, by using the simulated propagation
      patterns built with the earlier-developed exact solution of the mass-transfer
      equations for A* and C*. Our results prove that the obtained approximate solution
      of mass transfer equations is correct. They also show that the two-peak
      approximation facilitates finding k(+) and k(-) with a relative error of less
      than 10% if two peaks can be identified on a KCE electropherogram. Importantly,
      the condition of constant concentration of B is always satisfied in macroscopic
      approach to studying kinetics at equilibrium (MASKE) whether or not B is in
      excess to A* and C*, and, thus, the two-peak approximation is applicable to
      MASKE. It completes a toolset of fitting-free methods for processing MASKE data
      and makes MASKE a simple practical method for finding k(+) and k(-) of "fast",
      "slow", and "intermediate-rate" non-covalent interactions.

PMID- 22363930
TI  - Highly specific colorimetric recognition and sensing of sulfide with glutathione
      modified gold nanoparticle probe based on an anion-for-molecule ligand exchange
      reaction.
AB  - Colorimetric recognition and sensing of sulfide with high selectivity by virtue
      of glutathione-modified gold nanoparticle (GSH-AuNP) is presented. The assay is
      developed based on a specific anion-for-molecule ligand exchange reaction,
      through which sulfide replaces glutathione self-assembled on the AuNP. The unique
      feature of the GSH-AuNP probe makes it a novel colorimetric sensor for sulfide.

PMID- 22363931
TI  - Analysis of plant hormones by microemulsion electrokinetic capillary
      chromatography coupled with on-line large volume sample stacking.
AB  - A novel method of microemulsion electrokinetic capillary chromatography (MEEKC)
      coupled with on-line large volume sample stacking was developed for the analysis
      of six plant hormones including indole-3-acetic acid, indole-3-butyric acid,
      indole-3-propionic acid, 1-naphthaleneacetic acid, abscisic acid and salicylic
      acid. Baseline separation of six plant hormones was achieved within 10 min by
      using the microemulsion background electrolyte containing a 97.2% (w/w) 10 mM
      borate buffer at pH 9.2, 1.0% (w/w) ethyl acetate as oil droplets, 0.6% (w/w)
      sodium dodecyl sulphate as surfactant and 1.2% (w/w) 1-butanol as cosurfactant.
      In addition, an on-line concentration method based on a large volume sample
      stacking technique and multiple wavelength detection was adopted for improving
      the detection sensitivity in order to determine trace level hormones in a real
      sample. The optimal method provided about 50-100 fold increase in detection
      sensitivity compared with a single MEEKC method, and the detection limits (S/N =
      3) were between 0.005 and 0.02 MUg mL(-1). The proposed method was simple, rapid
      and sensitive and could be applied to the determination of six plant hormones in
      spiked water samples, tobacco leaves and 1-naphthylacetic acid in leaf
      fertilizer. The recoveries ranged from 76.0% to 119.1%, and good
      reproducibilities were obtained with relative standard deviations (RSDs) less
      than 6.6%.

PMID- 22363932
TI  - A fluorescence enhancement-based sensor for hydrogen sulfate ion.
AB  - Sugar-aza-crown ether-based cavitand 1 can act as a selective turn-on
      fluorescence sensor for hydrogen sulfate ion in methanol among a series of tested
      anions. Spectroscopic studies, particularly NMR spectroscopy, revealed that the C
      H hydrogen bonding between 1,2,3-triazole ring of cavitand 1 and hydrogen sulfate
      ion is crucial for the high selectivity of the receptor for hydrogen sulfate.

PMID- 22363933
TI  - Stamp transfer electrodes for electrochemical sensing on non-planar and oversized
      surfaces.
AB  - This article describes a new alternative approach to the fabrication of printed
      electrochemical sensors and biosensors based on the transfer of electrode
      patterns comprising common conductive and insulating inks from elastomeric stamps
      to a wide variety of rigid and flexible substrates. This simple, low cost, yet
      robust methodology is demonstrated to be well-suited for the formation of
      electrochemical sensors on non-planar substrates and large objects/structures,
      which have traditionally been off-limits to conventional screen printing
      techniques. Furthermore, the stamped electrode devices are shown to exhibit
      electrochemical performance that rivals that of their screen printed counterparts
      and display resilience against severe mechanical deformation. The stamp transfer
      approach is further extended to the demonstration of epidermal electrochemical
      sensors through the transfer of the electrode patterns directly onto the skin.
      The resulting sensors demonstrate a wide range of usability, from the detection
      of various physiological analytes, including uric acid on the skin, to the
      identification of residues originating from the handling of munitions and
      explosives. The migration of printable electrochemical sensors to non
      conventional (non-planar and/or oversized) surfaces provides new opportunities
      within the personal healthcare, fitness, forensics, homeland security, and
      environmental monitoring domains.

PMID- 22363934
TI  - Helical polymer brushes with a preferred-handed helix-sense triggered by a
      terminal optically active group in the pendant.
AB  - Helical polymer brushes with a preferred-handed helix-sense composed of a
      poly(phenylacetylene) backbone and poly(phenyl isocyanate) pendants are
      synthesized. The helix-sense of the backbone is effectively controlled by the
      helical chirality of the pendants, which is triggered by an optically active
      group introduced at the pendant terminal.

PMID- 22363935
TI  - Isotope-coded, fluorous photoaffinity labeling reagents.
AB  - A pair of isotope-coded, fluorous photoaffinity labeling reagents has been
      developed and coupled with a peptide. The modified peptides form adducts with
      methanol upon light illumination, which show characteristic isotope labeling
      patterns in mass spectra and can be separated from other peptides through
      fluorous silica.

PMID- 22363936
TI  - Chemical communication: conductors and insulators of screw-sense preference
      between helical oligo(aminoisobutyric acid) domains.
AB  - (1)H NMR studies quantify the abilities of achiral amino acids to communicate a
      left-handed screw-sense preference from one helical Aib(4) domain to another:
      certain quaternary amino acids (e.g. Ac(6)c) act as effective conductors of
      conformational preference while others (e.g. diphenylglycine) acts as insulators.

PMID- 22363937
TI  - Copper(II)/phenanthroline-mediated CD-enhancement and chiral memory effect on a
      meta-ethynylpyridine oligomer.
AB  - meta-Ethynylpyridine 18-mer associates with octyl beta-D-glucopyranoside to show
      an induced circular dichroism (CD) band at around 337 nm in CH(2)Cl(2). The
      addition of copper(II) triflate and o-phenanthroline enhanced the CD band. Even
      when an equimolar amount of beta-L-glucopyranoside was added to make the system
      racemic, the CD was memorized and remained for several weeks.

PMID- 22363938
TI  - Relay catalysis: combined metal catalyzed oxidation and asymmetric iminium
      catalysis for the synthesis of bi- and tricyclic chromenes.
AB  - A catalytic asymmetric oxidative iminium-allenamine cascade allows the use of
      propargyl alcohols as stable substrates and yields valuable chiral bicyclic 4H
      chromenes. A subsequent Michael addition-condensation domino reaction provides
      complex tricyclic 4H-chromenes in a highly enantioselective fashion.

PMID- 22363939
TI  - Iron-iron oxide core-shell nanoparticles are active and magnetically recyclable
      olefin and alkyne hydrogenation catalysts in protic and aqueous media.
AB  - We report for the first time the use of iron-iron oxide core-shell nanoparticles
      for the hydrogenation of olefins and alkynes under mild conditions in ethanol and
      in an aqueous medium. This catalyst proves robust towards the presence of
      oxidants, such as oxygen and water, is magnetically recoverable and shows
      selectivity towards the less activated double bonds.

PMID- 22363940
TI  - SnSe2 quantum dot sensitized solar cells prepared employing molecular metal
      chalcogenide as precursors.
AB  - A kind of molecular metal chalcogenide, (N(2)H(4))(3)(N(2)H(5))(4)Sn(2)Se(6)
      complex, was synthesized in the hydrazine solution and employed as the precursors
      for SnSe(2) deposition on TiO(2) nanocrystalline porous films. A power conversion
      efficiency of 0.12% under AM 1.5, 1 sun was obtained for the SnSe(2) sensitized
      TiO(2) solar cells.

PMID- 22363941
TI  - Are plasma level and CYP genotypes predictors of liver injury in an Ethiopian
      population?

PMID- 22363942
TI  - Do genetic polymorphisms of nevirapine metabolic, transport and antigen
      recognition enzymes play a role in nevirapine toxicity risk?

PMID- 22363943
TI  - Education: Outside the box.

PMID- 22363944
TI  - Radioembolization for the treatment of liver tumors general principles.
AB  - Radioembolization aims to selectively target radiation to all liver tumors while
      limiting the dose to normal liver parenchyma. The deposition of yttrium-90
      ((90)Y) microspheres delivered through the hepatic artery are preferentially
      implanted within liver tumors in a 3:1 to 20:1 ratio compared with a normal
      liver. The principles and mode of action of radioembolization are fundamentally
      different from the conventional embolization of liver tumors through
      transarterial embolization or chemoembolization. A meticulous work-up, involving
      computed tomography scanning, contrast-enhanced magnetic resonance imaging, and
      transfemoral hepatic angiogram, is essential to assess the appropriateness of the
      patient for treatment. A simulation of the treatment, done with technetium-99m
      labeled macroaggregated albumin particles, which approximate the size of
      microspheres, is used to identify the shunting of microparticles to the lungs or
      gastrointestinal tract, thus helping to determine patient selection. Whole-liver
      or unilobar treatment approaches are chosen according to the anatomic
      distribution of the tumors, concomitant factors affecting liver function, and
      institutional preferences. Optimal periprocedural care, discharge planning, and
      follow-up care are essential to assess treatment response and ensure that short
      term side effects of radioembolization are adequately managed. The expanding
      literature on radioembolization shows that this is an effective treatment for the
      management of both primary and metastatic tumors.

PMID- 22363945
TI  - [Correction of a mandibular alveolar protrusion using maxillary miniscrew
      anchorage in the treatment of a Class II division 1 malocclusion].
AB  - This article describes a relatively simple method of reducing a mandibular
      alveolar protrusion without compensatory extraction of mandibular bicuspids or
      advancement of anterior teeth in the treatment of a Class II division 1
      malocclusion. The use of well-planned skeletal anchorage specifically adapted to
      each specific situation is also well elucidated.

PMID- 22363946
TI  - [Root resorption associated to orthodontic treatment: a clinical case].
AB  - Root resorption associated to orthodontic treatment is of multiple etiologies and
      a non intentional iatrogenic side effect which exists in almost all the
      orthodontic treatment. This clinical case of an apparently healthy patient
      illustrates the occurrence during the orthodontic treatment of a root resorption
      interesting the left central incisor, victims of previous traumatism and
      presenting a moderate periodontal attachment loss. The orthodontic treatment was
      carried out with light and continuous forces and a per-orthodontic periodontal
      maintenance in respect of periodontal requirements. As soon as the root
      resorption on the left central incisive was diagnosed, the active orthodontic
      treatment was interrupted in order to stabilize the lesion and a regular clinical
      and radiological monitoring was established.

PMID- 22363947
TI  - Detailed protocols and practical advice on a variety of modern approaches to the
      study of leucocytes and their products. Preface.

PMID- 22363948
TI  - A review of Medicaid rate reductions in 2011.

PMID- 22363949
TI  - Nurses braced for strike day as anger builds over pensions plan.

PMID- 22363950
TI  - "Keeping our mission, changing our system": translation and organizational change
      in natural foods co-ops.
AB  - Institutional theory has played a central role in the study of organizations for
      over half a century, but it often overlooks the actions of the people who bring
      organizations to life. This article advances an inhabited approach to
      institutional analysis that foregrounds the creativity of organizational members.
      It argues that people use local cultures to translate and respond to
      institutional pressures. The article analyzes qualitative data from
      countercultural co-op stores that have been pushed to conform to mainstream forms
      of business organization by a competitive market and demonstrates that
      translation explains why outcomes that institutional theory would not predict
      have come to pass.

PMID- 22363956
TI  - Women performers and prostitutes in Medieval India.
AB  - Music and dance, the esoteric performing arts, were markers of culture in
      medieval India. A number of these differing forms developed into well-recognized
      and reputed arts over time. The practitioners were, accordingly, regarded as
      agents of refinement and culture. At the same time, music and dance were also
      among the most popular forms of entertainment and physical pleasure. This aspect
      remained crucial in classifying musicians, singers and dancers as entertainers,
      alongside prostitutes. While the labelling together might have reduced the status
      of performers at times, the labelling hardly remained fixed. Certain
      practitioners, even if involved in practices otherwise considered immoral, could
      remain within the elite circle, while for others the 'evil' characteristics got
      emphasized. There were, within the class of women who prostituted themselves,
      courtesans trained in the skills of music and dancing and educated in the fine
      arts, who were treated more as embodiments of culture. These categories-artists,
      skilled entertainers, courtesans-were quite fluid, with the boundaries seemingly
      fused together. Still, there were certainly some distinctions among the
      categories and those did not totally disappear, affording sanctity and purity to
      certain kinds of performers and allowing them to claim distinctiveness. Notably,
      the class of courtesans clearly stood apart from the common prostitutes. The
      attempt in this article is to look at different categories of women performers
      and prostitutes, their apparent coalescing boundaries and specialities as a
      separate group, their societal position, their shifting roles and the changes
      that affected their status. In this, it is worthwhile to consider the state's
      attitude towards them, besides societal views that remained quite diverse.

PMID- 22363957
TI  - A busman's holiday in the not-so-lonely crowd: business culture, epistolary
      networks, and itinerant homosexuality in mid-twentieth-century America.

PMID- 22363958
TI  - The ghost that slayed the mandate.
AB  - Virginia v. Sebelius is a federal lawsuit in which Virginia has challenged
      President Obama's signature legislative initiative of health care reform.
      Virginia has sought declaratory and injunctive relief to vindicate a state
      statute declaring that no Virginia resident shall be required to buy health
      insurance. To defend this state law from the preemptive effect of federal law,
      Virginia has contended that the federal legislation's individual mandate to buy
      health insurance is unconstitutional. Virginia's lawsuit has been one of the most
      closely followed and politically salient federal cases in recent times. Yet the
      very features of the case that have contributed to its political salience also
      require its dismissal for lack of statutory subject matter jurisdiction. The
      Supreme Court has placed limits on statutory subject matter jurisdiction over
      declaratory judgment actions in which a state seeks a declaration that a state
      statute is not preempted by federal law--precisely the relief sought in Virginia
      v. Sebelius. These statutory limits are a sea wall; they keep out, on statutory
      grounds, some suits that should otherwise be kept out on Article III grounds. The
      statutory and constitutional limits on federal jurisdiction over suits like
      Virginia v. Sebelius insulate federal courts from the strong political forces
      surrounding lawsuits that follow from state statutes designed to create federal
      jurisdiction over constitutional challenges by states to federal law. This
      Article identifies previously neglected jurisdictional limits, shows why they
      demand dismissal of Virginia v. Sebelius, and explains why it is appropriate for
      federal courts to be closed to suits of this type.

PMID- 22363959
TI  - State sovereign standing: often overlooked, but not forgotten.
AB  - Critics of Virginia's challenge to the constitutionality of the Patient
      Protection and Affordable Care Act have asserted that Virginia lacked standing to
      even raise the issue. Such criticism is inconsistent with foundational
      understandings of the role of states in providing a check on federal power and
      with the modern standing jurisprudence of the Supreme Court, especially as
      reflected in the Court's decisions regarding a state's sovereign interest in
      defending its code of laws. This Article demonstrates that, as a matter of
      constitutional design and history, as well as under relevant precedents, Virginia
      clearly had and has standing to bring its challenge.

PMID- 22363960
TI  - Bad medicine: prescription drugs, preemption, and the potential for a no-fault
      fix.
AB  - For decades, federal regulation of pharmaceutical drugs and medical devices has
      worked hand in hand with state tort claims to protect the health and safety of
      the American public. Now, a new trend toward preemption endangers this scheme. In
      recent years, the Supreme Court has given increasing deference to agency
      assertions about their preemptive authority and has found preemption in an
      increasing number of cases. In the process, the Supreme Court has preempted
      claims for medical device injuries and left claims for pharmaceutical harms in a
      precarious position. The elimination of common law claims for drug and device
      harms will leave holes in the FDA's regulatory scheme, endangering the health and
      safety of Americans. It will also prevent ordinary Americans from seeking
      compensation for their injuries--even those injuries caused by manufacturer
      malfeasance. This Article proposes that Congress create a no-fault compensation
      scheme for drugs and medical devices to close these gaps. Such a scheme could be
      both practical and politically possible, satisfying manufacturers, tort
      reformers, patients, and plaintiffs' lawyers alike.

PMID- 22363961
TI  - The quality of emergency medical services.
AB  - Although Emergency Medical Services (EMS) is a crucial part of the health care
      system, there is relatively little research on the quality of those services. EMS
      agencies often measure their performance using criteria such as response time or
      total prehospital time. But larger scale studies that cross counties and
      providers are rare. This Issue Brief summarizes two studies that use
      comprehensive, longitudinal data from one state to assess the demographic,
      geographic, and professional factors that affect EMS performance.

PMID- 22363963
TI  - Tracking networks: linking health and the environment.

PMID- 22363962
TI  - How the newly insured use health services: a lesson for the U.S. from Medicare.
AB  - The Congressional Budget Office estimates that about 32 million previously
      uninsured people will gain coverage by 2016, when health care reforms are fully
      implemented. But will these newly insured people use the health care system in
      the same ways as others? Is insurance enough to change patterns of use? The
      example of Medicare may provide some insight. This Issue Brief summarizes
      research that investigates how health care use and patterns change among the
      uninsured and insured once they gain Medicare coverage at age 65.

PMID- 22363964
TI  - The burden of prescription drug overdoses on Medicaid.

PMID- 22363965
TI  - Charlotte Wolff's contribution to bisexual history and to (sexuality) theory and
      research: a reappraisal for queer times.

PMID- 22363966
TI  - Carl Linnaeus and the visual representation of nature.
AB  - The Swedish naturalist Carl Linnaeus (1707-1778) is reputed to have transformed
      botanical practice by shunning the process of illustrating plants and relying on
      the primacy of literary descriptions of plant specimens. Botanists and historians
      have long debated Linnaeus's capacities as a draftsman. While some of his
      detailed sketches of plants and insects reveal a sure hand, his more general
      drawings of landscapes and people seem ill-executed. The overwhelming consensus,
      based mostly on his Lapland diary (1732), is that Linnaeus could not draw. Little
      has been said, however, on the role of drawing and other visual representations
      in Linnaeus's daily work as seen in his other numerous manuscripts. These
      manuscripts, held mostly at the Linnean Society of London, are peppered with
      sketches, maps, tables, and diagrams. Reassessing these manuscripts, along with
      the printed works that also contain illustrations of plant species, shows that
      Linnaeus's thinking was profoundly visual and that he routinely used visual
      representational devices in his various publications. This paper aims to explore
      the full range of visual representations Linnaeus used through his working life,
      and to reevaluate the epistemological value of visualization in the making of
      natural knowledge. By analyzing Linnaeus's use of drawings, maps, tables, and
      diagrams, I will show that he did not, as has been asserted, reduce the
      discipline of botany to text, and that his visual thinking played a fundamental
      role in his construction of new systems of classification.

PMID- 22363967
TI  - "My goose child Martina": the multiple uses of geese in the writings of Konrad
      Lorenz.
AB  - In 1935, the graylag goose Martina (1935-?) hatched from an egg in the home of
      the zoologist Konrad Lorenz (1903-1989). Martina imprinted on Lorenz, slept in
      his bedroom, mated with the gander Martin, and flew off in 1937. Over the
      following decades, Konrad Lorenz helped to establish the discipline of ethology,
      received a share of the 1973 Nobel Prize in Physiology or Medicine, and continued
      to write about his famous goose Martina. This essay examines the different
      instantiations of the geese in general, and Martina in particular, in Lorenz's
      writings aimed at readerships that included prewar zoologists, National Socialist
      psychologists, and popular audiences from the 1930s to 1980s. By developing an
      animal with her own biography, Lorenz created an individual whose lived and
      rhetorical agency made her especially well suited to perform widely divergent
      aspects of his evolving science. While a significant literature in the history of
      science has explored the standardization and stabilization of animals in science,
      I show how Lorenz's creation of a highly protean and increasingly public Martina
      was co-constitutive of the establishment of the science and public persona.

PMID- 22363968
TI  - [Musicians and craniofacial pain].

PMID- 22363969
TI  - [Coronary computed tomography: current role and future perspectives for
      cardiovascular risk stratification].
AB  - Atherosclerotic coronary artery disease (CAD) is a major cause of morbidity and
      mortality. The majority of cardiovascular events, more than 50% of CAD deaths,
      occur in previously asymptomatic individuals at intermediate cardiovascular risk,
      highlighting the relevance of accurate individual risk assessment to decrease
      cardiovascular events through more appropriate targeting of preventive measures.
      In the last decades, the development of non-invasive imaging techniques have
      prompted interest in imaging of atherosclerosis. Coronary computed tomography
      provides the opportunity to assess the deposition of calcium in the coronary tree
      and to non-invasively image coronary vessels. Both information are useful for
      risk stratification of asymptomatic subjects or of subjects with suspected CAD.

PMID- 22363970
TI  - [After ACC/AHA and ESC Guidelines: Pre-operative cardiological evaluation in non
      cardiac surgery: certainties, controversial areas and opportunities for a team
      approach].
AB  - A standardized and evidence-based approach to the cardiological management of
      patients undergoing noncardiac surgery has been recently defined by Task Forces
      of the American Heart Association (AHA), American College of Cardiology (ACC) and
      the European Society of Cardiology (ESC) that published their guidelines in 2007
      and 2009, respectively. Both the recommendations moved from risk indices to a
      practical, stepwise approach of the patient, which integrates clinical risk
      factors and test results with the estimated stress of the planned surgical
      procedure. In the present paper the main topics of the guidelines are discussed,
      and moreover, emphasis is placed on four controversial issues such as the use of
      prophylactic coronary revascularization in patients with myocardial ischemia, the
      perioperative management of patients with congestive heart failure, the routine
      use of betablockers and statins, and, finally, the management of antiplatelet
      therapies in patients with coronary stents. In addition to promoting an
      improvement of immediate perioperative care, the preoperative cardiological
      evaluation should be a challenge for identifying subjects with enhanced risk of
      cardiovascular events, who should be treated and monitored during a long-term
      follow-up.

PMID- 22363971
TI  - [Clinical and therapeutic value of carotid intima-media thickness].
AB  - Carotid Intima Media Thickness (IMT) has been widely used to predict
      cardiovascular events in primary and secondary prevention studies. Yet, the power
      of IMT to reclassify risk level on top of conventional risk assessment based on
      classical risk factors remains unsettled. In fact, recent data indicate that the
      prognostic power of IMT is lower than that provided by the identification of
      carotid plaques. The role of IMT as surrogate endpoint to assess the efficacy of
      cardiovascular protective therapies is also still debated. In fact, no studies
      have ever been designed and powered to show a relationship between changes in
      carotid IMT during follow-up and cardiovascular events. Recently, two meta
      analysis of trials using IMT as surrogate endpoint failed to demonstrate an
      association between IMT regression and cardiovascular events. The reasons for the
      lack of predictive role for changes in IMT are uncertain. It has been shown that
      IMT is not a pure atherosclerotic index, being substantially affected by age and
      hemodynamic factors including blood pressure and vessel wall shear stress. In
      addition, the status of carotid vessels does not strictly reflect that of
      coronary arteries. Finally, intra and inter-observer variability of measurements
      may further limit the association between IMT changes in individual patients and
      cardiovascular risk. Thus, IMT represents a valuable risk marker in population
      studies but its role for tailoring cardiovascular therapy in clinical practice
      remains currently uncertain.

PMID- 22363972
TI  - Cardiovascular prevention and rehabilitation for patients with ventricular assist
      device from exercise therapy to long-term therapy. Part II: long-term therapy.
AB  - Over the years left ventricular assist devices (VADs) have become more durable
      and reliable, smaller, simpler, easier to implant and more comfortable. The
      extensive experience now acquired shows successful hospital discharge with VAD
      use. We are entering an era in which long-term mechanical circulatory support
      will play an increasing role in the approach to end-stage heart failure (HF); at
      the same time, the extension of VADs into destination therapy has revealed the
      limitations of our understanding of these populations. This second paper on
      cardiovascular prevention and rehabilitation for patients with left VADs will
      deal with the management of patients outside the highly specialized HF centers
      and surgical setting, with particular focus on postoperative patient management.
      Outpatient management of VAD patients is time-intensive, and a multidisciplinary
      approach is ideal in long-term care. Although the new devices have definite
      advantages over the older pumps, some challenges still remain, i.e. infection,
      stroke, device thrombosis, gastrointestinal bleeding, recurrent HF symptomatology
      with or without multisystem organ failure, and occurrence of ventricular
      arrhythmias.

PMID- 22363973
TI  - A case of quadricuspid aortic valve characterized by echocardiography and
      magnetic resonance imaging.
AB  - We report a rare subtype of quadricuspid aortic valve (QAV) associated with
      moderate aortic regurgitation in a 17-year old woman symptomatic for
      palpitations. The patient was admitted to our department for cardiac evaluation
      due to a previous diagnosis of bicuspid aortic valve; she underwent a new two
      dimensional echocardiography revealing a rare type of quadricuspid aortic valve
      with a moderate regurgitation. For further investigating potentially associated
      abnormalities, patient was referred to Cardiac MRI; MRI showed no other
      abnormalities and confirmed echocardiographic findings. Quadricuspid aortic valve
      is a rare form of congenital valvular anomaly often occasionally diagnosed. In
      most cases this malformation causes a valve dysfunction, commonly aortic
      regurgitation, and can be associated with other cardiac abnormalities such as
      ventricular or atrial septal defect, anomalies of coronary arteries, patent
      ductus arteriosus, subaortic fibromuscolar stenosis and mitral valve
      malformation.

PMID- 22363974
TI  - Acute heart failure in an adult with unrecognized congenital heart disease.
AB  - We report a case of 46 year-old man, admitted to our Department for a possible
      massive pulmonary embolism. Instead, diagnosis of Tetralogy of Fallot was
      established by echocardiography and cardiac catetherization.

PMID- 22363975
TI  - Atypical response of class IC atrial flutter to adenosine.
AB  - We report the case of a 67-year-old female with a wide QRS complex tachycardia at
      180 bpm. A diagnosis of class IC atrial flutter with aberrant ventricular
      conduction caused by flecainide therapy was formulated. Intravenous adenosine
      administration resulted in adequate slowing of the ventricular rate and
      normalization of QRS complexes. Restoration of sinus rhythm was achieved with
      intravenous amiodarone. The response to adenosine confirmed the diagnosis of
      supraventricular tachycardia with aberrant conduction, but the transition from
      arrhythmia onset to restoration of sinus rhythm showed interesting peculiarities.

PMID- 22363976
TI  - [Bitter sweet journey].

PMID- 22363977
TI  - [Habenula--a new target for treatment of intractable depression].
AB  - Despite substantial advancement in psychopharmacological and electro-magnetic
      treatments over the last decades on the depression patients, there are non
      responders remain with a chronic disease and high suicidal risk yet. Deep brain
      stimulation (DBS) is now being experimentally to treat the intractable depression
      and yielded an impressive therapeutic benefit, and especially few adverse effect
      occurred. The beneficial action of DBS is closely related to the stimulation sit.
      And the efficacy of high frequency stimulation of lateral habenula is one of the
      best choice. In depression, the concentration of 5-HT released by the raphe
      nuclei is decreased. It's due to mainly the overactivation of the lateral
      habenula. High frequency stimulation of lateral habenula impairs the activation
      of lateral habenula, and the inhibitory effect of lateral habenula on raphe
      nuclei is decreased. Then, the 5-HT concentration released by the raphe nuclei is
      increased, the pathological changes of depression is eliminated. The lateral
      habenula could be a promising novel target for BDS in the cases of intractable
      depression.

PMID- 22363978
TI  - [Structural plasticity associated with drugs addiction].
AB  - An essential feature of drug addiction is that an individual continues to use
      drug despite the threat of severely adverse physical or psychosocial
      consequences. Persistent changes in behavior and psychological function that
      occur as a function of drugs of abuse are thought to be due to the reorganization
      of synaptic connections (structural plasticity) in relevant brain circuits
      (especially the brains reward circuits). In this paper we summarized evidence
      that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced
      persistent changes in the structure of dendrites and dendritic spines on cells in
      relevant brain regions. We also approached the potential molecular mechanisms of
      these changes. It is suggested that structural plasticity associated with
      exposure to drugs of abuse reflects a reorganization of patterns of synaptic
      connectivity in these neural systems, a reorganization that alters their
      operation, thus contributing to some of the persistent sequela associated with
      drug use-including addiction.

PMID- 22363979
TI  - [Research of endoplasmic reticulum stress and cardiovascular diseases].
AB  - Endoplasmic reticulum stress is a newly discovered pathway of apoptosis,
      following the death receptor signaling and mitochondrial pathways. Moderate
      stress triggers the unfolded protein response (UPR) to rsstore the cell function.
      However, if the stress is severe and/or prolonged, the ER also initiates
      apoptotic signaling that includes CHOP, ASK1/JNK and caspases pathways. Recent
      studies have found that endoplasmic reticulum stress plays an important role in
      the development of various cardiovascular diseases. Also, extensive research has
      shown that it can bring about protective effects on myocardial cells through the
      intervention of the relevant pathways, which may provide us with new therapeutic
      targets for heart diseases.

PMID- 22363980
TI  - [Protein kinase C and morphine tolerance].
AB  - Protein kinase C (PKC) belongs to the AGC (cAMP-dependent protein kinase/PKG/PKC)
      protein kinase family which plays an important role in the morphine-induced
      desensitization of R-opioid receptors. This cellular process is believed to
      contribute to the development and maintenance of morphine tolerance. Therefore,
      the study of PKC signaling transduction on morphine tolerance has an important
      clinical significance. The present review summarizes the possible involvement of
      PKC in opioid tolerance.

PMID- 22363981
TI  - [Progresses in the study of unbalance of basal ganglia neurotransmitters in
      Parkinson's disease].

PMID- 22363982
TI  - [Regulation of soluble guanylyl cyclase and its role in the treatment of
      cardiovascular diseases].

PMID- 22363983
TI  - [Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein
      1: a new gene involved in plasma triglyceride metabolism].

PMID- 22363984
TI  - [Progress on the structural and functional study of Nrf1].

PMID- 22363985
TI  - [Research progress on the myocardial Na+/H+ exchange 1 and its role in
      ischemia/reperfusion].

PMID- 22363986
TI  - [Catestatin: a novel cardiovascular protective peptides].

PMID- 22363987
TI  - [Advancement on the structure and function of genes encoding crustacean
      chitinase].

PMID- 22363988
TI  - [The relationship between LXR/RXR and ABCA1 transmembrane-transport system with
      Alzheimer's disease].

PMID- 22363989
TI  - [The role of TGF-beta in the EMT of tumor cells].

PMID- 22363990
TI  - [Research on MSTN coordination body fat and skeletal muscle cell proliferation
      and differentiation and energy metabolization balance].

PMID- 22363991
TI  - [New approaches to the complex pathogenetic therapy of patients with chronic
      pancreatitis].

PMID- 22363992
TI  - [Pancreatic secretory trypsin inhibitor gene N34S mutation in patients with
      idiopathic chronic pancreatitis].
AB  - PURPOSE: To determine the frequency and prognostic significance of mutation N34S
      in the development of CP in a mixed Russian population. METHODS: The study
      included 83 patients with idiopathic CP and 103 healthy individuals. The
      diagnosis of CP was based on clinical and instrumental data in accordance with
      the criteria of M-ANNHEIM. Everyone involved in this study using PCR followed by
      restriction analysis performed the N34S mutation analysis in the gene for the
      ICU. RESULTS: N34S mutation was detected in 12 patients with CP and in 3 of the
      control group, which accounted for 14.6 and 2.9% respectively; p<0,05. The odds
      ratio (OR) of idiopathic CP in the presence of mutation N34S was 4.62 (95%
      confidence interval (CI): 1,21-18,37). The difference in frequency of homozygotes
      the mutant allele was statistically significant: 10.97 and 0.97% in the main and
      control groups, respectively; p<0,05. The presence of mutations did not affect
      the frequency and severity of functional disorders of the pancreas, but the
      mutation N34S was statistically significantly more common in patients with
      calcifying pancreatitis (p<0,01) and the presence of pseudocysts (p<0,05). OR the
      development of calcification in patients with the presence of N345 was 13.44 (95%
      CI: 6,29-23,78). CONCLUSION: These data suggest that the mutation N34S plays a
      significant role in the development of CP in the Russian population and can
      detect more than 10% of cases of idiopathic CP.

PMID- 22363993
TI  - [Chronic pancreatitis: microbe-intestinal tissue complex and systemic
      inflammatory response].
AB  - Today in Russian Federation, we observe significant growth of the chronic
      pancreatitis incidence with the depression of its therapy efficiency (more than
      20% of the patients) and complications rate growth. In many respects given
      tendency is associated with the inefficiency of traditional medications
      combination in the context of inflammation process reduction, gut dysbiosis
      correction and chronic inflammation reaction depression. Present-day studies
      indicates, that the grade and character of inflammation in the pancreas depends
      on the pro- and anti-inflammatory cytokines balance, which is associated with the
      elevation of the pathogenic microbiota concentration and permeability of the gut.
      We estimate clinical efficacy of complex treatment regimen (PPI, spasmolytic,
      multienzyme and prebiotic therapy) in the patients with chronic pancreatitis and
      its effect on chronic system inflammation. We established that efficacy of modern
      complex treatment regimen depends on its influence on chronic system inflammation
      and that prebiotics addition potentiates correction of dysbiotic changes in the
      gut microbial-tissular complex and reduces grade of system inflammation.

PMID- 22363994
TI  - [The systemic inflammatory response syndrome correction in acute destructive
      pancreatitis].
AB  - Acute pancreatitis is a disease of variable severity. In which some patients
      experience mild, self-limited attacks while others manifest a severe, highly
      morbid, and frequently lethal attack. The exact mechanisms by which diverse
      etiological factors induce an attack are still unclear. Recent studies have
      established the role played by inflammatory mediators in the pathogenesis of
      acute pancreatitis. In our research we have estimated influence of not steroid
      anti-inflammatory preparation on synthesis pro-and anti-inflammatory Cytokines at
      healthy donors and at patients with Acute pancreatitis.

PMID- 22363996
TI  - [Mesenchymal stromal cells transplantation in acute and chronic pancreatitis in
      rats].
AB  - Before using MSC transplantation in the clinic to conduct preclinical studies
      MSCs to animals with acute and chronic pancreatitis. Work out the timing and dose
      of MSCs. The rationale of MSCs transplantation for the regeneration of damaged
      pancreatic tissue. The essence of the experiments is to establish the existence
      of common pathogenetic mechanisms for the development of pathological processes
      and sanogenesis toxic damage of pancreatic tissue. The study was work out in the
      rat model of acute and chronic pancreatitis, to explore beneficial and adverse
      effects of allogeneic stem cells for regenerative-reduction processes. For cell
      transplantation using allogenic stromal cell fraction of bone marrow, the cell
      suspension was injected at a dose of 2 x 10(6) and 5 x 10(6) cells.

PMID- 22363995
TI  - [Lipid peroxidation in patients with acute and chronic pancreatitis].
AB  - OBJECTIVE: To assess the initial levels of lipid peroxidation (LPO) products in
      LDL and to study changes in oxidative resistance (OR) of precipitated LDL in
      acute and chronic pancreatitis patients (OP and CP). METHODS: were examined 39 CP
      patients and 37 OP patients, and the control group - 7 persons without pancreatic
      diseases and diabetes mellitus (DM). All CP patients were examined in the acute
      stage, OP patients - in the first 5 days after admission to hospital.
      Determination of LPO products in LDL and OR of LDL to Cu2+ - induced oxidation
      were carried out its own method (Ragino, 1998). RESULTS: In CP patients the
      initial level of LPO products in LDL was higher (8.9 +/- 1.5 nmol MDA/mg LDL
      protein) than in those in control group (5.3 +/- 0.8) and in OP patients (5.0 +/-
      0.5, p<0.05), and the OR of LDL is significantly lower than those in the control
      group. In AP and CP patients with permanent pain syndrome in the left
      hypochondrium initial level of LPO products in LDL is much higher (7.0 +/- 0.6,
      and 5.0 +/- 0.6, p = 0,016), and OR of LDL after 0, 5, 1 and 2 h incubation with
      Cu2+ (2 h: 31.7 +/- 1.8 and 23.2 +/- 1.9, p = 0.002) - much lower compared with
      AP and CP patients without pain. Only CP patients combined with DM type 2 were
      defined reducing the OR of LDL after 0.5, 1 and 2 h incubation with Cu2+.
      CONCLUSION: The activity of LPO in the blood and LDL were affected in AP and CP
      patients.

PMID- 22363997
TI  - [Pancreatic functional status after wedge resection of the duodenal wall and para
      pancreatic micro-irrigation].
AB  - RESEARCH OBJECTIVE: To study influence parapancreatic microirrigation on
      morphological and functional condition of a pancreas and transformations of
      enzymatic activity of blood serum and enzymatic activity of lymph of a chest
      lymphatic channel after an operative trauma of a duodenum. MATERIAL AND METHODS:
      Research is executed on 140 not purebred dogs which have been divided into six
      groups and united in two series. In the first series (30 dogs) were studied
      changes pancreatic exosecretion in the postoperative period of resection of
      duodenum (group 1.1), in the postoperative period of resection of duodenum with
      preliminary infiltration of a parapancreatic tissue of 0.5% by a solution of
      Novocain (group 1.2) and after resection of duodenum with application
      parapancreatic microirrigation (group 1.3). In the second series (110 dogs) were
      studied frequency of development of acute pancreatitis, enzymatic activity of
      blood serum and enzymatic activity of lymph of thoracal lymphatic duct after
      resection of duodenum (group 2.1) and in the postoperative period of resection of
      duodenum with preliminary infiltration of a parapancreatic tissue of 0.5% by a
      solution of Novocain (group 2.2) and after resection of duodenum with application
      parapancreatic microirrigation (group 2.3). RESULTS: Application parapancreatic
      microirrigation does not lead to oppression pancreatic exosecretion at the first
      o'clock after duodenotomy, and substantially reduces the pancreatic
      hypersecretion observed in the postoperative period of resection of a duodenum.
      In addition, application parapancreatic microirrigation reduces frequency of
      development of acute pancreatitis and promotes less expressed increase enzymatic
      activity of blood serum and enzymatic activity of lymph thoracal lymphatic duct
      at development of the given complication after operational trauma of duodenum in
      comparison with resection of duodenum and after a resection of a duodenum
      executed against infiltration of a parapancreatic tissue of 0.5% by a solution of
      Novocain.

PMID- 22363998
TI  - [The lungs as target organ in inflammatory bowel disease: clinical and
      experimental study].

PMID- 22363999
TI  - [Ultrasound diagnosis of extrahepatic portal hypertension in chronic
      pancreatitis].
AB  - AIM: To evaluate the potential of the color duplex scanning in revealing of the
      portal hypertension in patients with chronic pancreatitis. MATERIALS AND METHODS:
      94 patients with chronic pancreatitis were investigated. In 61 patients (65%)
      pancreatitis was complicated by extrahepatic portal hypertension (EHPH) and 31
      patients (35%) were without signs of rising of the portal pressure. RESULTS:
      Investigations in B-regime have shown that in patients with EHPH chronic
      calculous pancreatitis was revealed in 48%, development of pancreatic
      hypertension in 75%, increase of the pancreas head up to more than 40 mm in 58%
      of patients. We did not reveal statistically significant differences in pseudo
      cysts in pancreas, extension of extrahepatic and intrahepatic ducts and
      infiltrative changes in parapancreatic cellular tissue in patients with and
      without EHPH. A development of EHPH in 31 (51%) patients was preconditioned by an
      extravasal compression of veins of portal system, combination of extravasal
      compression with thrombosis was found in 11 (18%) patients, in 12 (20%) patients
      thrombosis of the magistral veins of portal system was revealed and in 7 (11%)
      patients hemodynamics was not changed. Resections were found to be preferable
      operations for recovery of portal circulation. Increase and normalization of
      portal circulation found after transversal section of pancreas (Beger operation,
      pancreo-duodenal resection, distal resection of pancreas). A tendency to
      normalization of the blood flow was observed after the Frey operation.

PMID- 22364000
TI  - [Tactic of treatment of complicated pancreatic pseudocysts].

PMID- 22364001
TI  - [Peculiarities of diabetes mellitus course in chronic pancreatitis].
AB  - In order to identify features of the course pancreatic diabetes and discussion of
      the principles of conservative therapy were examined 66 patients with CP in age
      of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed
      with formation of calcification of pancreas, 13 - pancreatic cysts, and 5
      revealed pseudo tumor form of CP, 10 patients had clinical and laboratory
      evidence of diabetes. Concerning CP complicated course were performed 14
      resection and 11 draining operations on the pancreas. Based on clinical,
      instrumental and laboratory data was made the diagnosis of CP. Exocrine
      pancreatic function was assessed on the results of the breath test, using 13C
      trioktanaine, which is applied for exocrine pancreatic function in vivo test. The
      content of C-peptide was investigated by enzyme-linked immunosorbent assay
      (ELISA). The data indicate pancreatic exocrine function decrease in patients with
      CP with complications and without complications in compare with the norm of 44%
      (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test.
      Significant decrease of the cumulative output tags based on the test data of
      patients with CP and pancreatic calcification, diabetes mellitus, after resection
      surgery with CP complications, and there were significant differences in compare
      with a group of patients with CP without complications (p = 0.5). The level of C
      peptide in these groups of patients decreased significantly in compare with a
      group of patients with CP without complications, and patients with CP and
      Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie
      below the minimum values of norm. Obtained a direct correlation between the level
      of C-peptide and indicators breath test in patients after resection HP (r = 0,84,
      p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were
      negative, which proves the specific type of Diabetes at HP. Antibodies to insulin
      can be detected only at diabetes type 1. In 7 patients with CP and CD detected
      calcification, 5 patients performed resection surgery, 3 patients had
      calcification and conducted the pancreas resection. Thus, we can conclude that in
      patients with CP and formation of pancreas calcification, pancreas resections may
      predict the development of diabetes.

PMID- 22364002
TI  - [Study of clinical efficiency of essential phospholipids and silymarin
      combination in nonalcoholic and alcoholic steatohepatitis].
AB  - The issues of steatohepatitis treatment in the pathogenesis of which a major role
      plays lipid accumulation in hepatocyte and increased processes of free radical
      oxidation of lipids. Developed a method of treatment of patients with alcoholic
      and nonalcoholic steatohepatitis with the inclusion of a combination of essential
      phospholipids (EPL) and silymarin (SM). A comparative assessment of results of
      treatment with the inclusion of a combination of EPL and SM, Essentiale and
      Carsil in 60 patients with alcoholic and nonalcoholic steatohepatitis. Revealed
      the preferential efficiency of combination EPL and SM in these patients in regard
      of shortening the time clinical manifestations of disease, reducing transaminase
      activity, normalization of the cholestasis and cholesterol. Given practical
      recommendations of treatment patients with alcoholic and nonalcoholic
      steatohepatitis with the inclusion of a combination of EPL and CM.

PMID- 22364003
TI  - [Significance of biliary dysfunction in the pathogenesis of gallstone disease].
AB  - The paper shows the role of biliary dysfunction in the formation of biliary
      sludge. Found that among all motor dysfunction themost common is reduction of
      contractile function of the gallbladder (in 63.3% of cases), which is combined
      with 73.2% Oddi's sphincter hypertonus. T The combination of ursodeoxycholic acid
      (UDCA) with mebeverine has a better effect than monotherapy with UDCA, as
      increases the frequency of relief of biliary dyspepsia symptoms, normalizes the
      biliary tract functional status and 95% of cases leads to the elimination of
      biliary sludge.

PMID- 22364004
TI  - [Biliary pancreatitis].
AB  - It is provided the basic information of the etiopathogenesis, diagnosis of
      biliary pancreatitis, drug treatment of patients with holetsistolitiaz, and the
      information of biliary pancreatitis's prevention.

PMID- 22364005
TI  - [Enterofuril eradication therapy in chronic inflammatory diseases of the upper
      digestive tract].

PMID- 22364006
TI  - [Use of serum tumor markers in the diagnosis of malignant tumors of the digestive
      system].
AB  - The article is devoted to the main OncoMarkers, which are used in the case of
      malignant growth in digestal organs, their efficient administration in the
      medical practise and diagnostic importance.

PMID- 22364007
TI  - [Idiopathic pancreatitis].
AB  - The basic current information on etiopathogenesis, diagnosis and treatment of
      patients with idiopathic pancreatitis.

PMID- 22364008
TI  - [Diagnosis and surgical treatment of pancreatic cancer].
AB  - Despite sustained efforts, intensive research has not been proven successful to
      reveal risk factors, which relevantly influence early diagnostics or effective
      treatment of pancreatic carcinoma. Principally, it must be noted, that currently
      no ideal tumor marker exists for the (early) detection of pancreatic carcinoma.
      The most important imaging modalities are high-resolution computed tomography,
      abdominal ultrasound, and endosonography. Surgical procedures in therapy have
      become more and more standardised and lead to a decrease in morbidity and
      mortality on the one hand and to an increase in resectability on the other hand.
      Pylorus-preserving partial pancreaticoduodenectomy is the treatment of choice for
      a tumor of the pancreatic head, whereas resection of the left pancreas (including
      splenectomy) is the standard therapy for carcinomas of the pancreatic tail. In
      all cases, a local systematic lymphadenectomy is mandatory; hence the prognostic
      gain of an extended lymphadenectomy remains indeterminate. An infiltration of
      mesenteric and portal veins does not prevent respectability, as long as by venous
      resection an R0 status can be achieved. However arterial involvement in general
      excludes resection. Patients with marginally resectable or locally non-resectable
      tumors should be recruited into neoadjuvant radiochemotherapy trials since one
      third of these patients could be considered for potentially curative resection.
      However the majority of pancreatic cancer patients show locally unresectable or
      metastasized disease and therefore palliative treatment concepts are needed.
      Both, endoscopic or percutaneous stenting procedures and operative bypass
      surgery, are safe and reach high success rates.

PMID- 22364009
TI  - [Painless course of chronic calcificated pancreatitis manifesting as
      hyperglycemia].
AB  - The clinical case of chronic calcifying pancreas (CCP) was described. It was
      reveal that obligate sign CCP as a painful syndrome can disappeared in some
      circumstances, in particular when the patient refused of smoking and alcohol
      intake.

PMID- 22364010
TI  - [Reproductive disorders in women with celiac disease: effect of etiotropic
      therapy].
AB  - The study included 132 women (average age 38.5 +/- 1.17 years) with HC observed
      in the CSRIG from 2000 to 2010. Comparison group consisted of 105 women (average
      age 38.7 +/- 1.6 years) mainly with functional bowel disorders (irritable bowel
      syndrome, functional constipation, functional meteorism, inert colon). Take into
      account the information relating to obstetric and gynecological history, Physical
      and laboratory signs of malabsorption syndrome (MS), studies of antibodies to
      alpha-gliadin immunoglobulin (IG), Class A (AHA) and tissue transglutaminase
      (AtTG). Reproductive disorders in women with celiac disease are significantly
      more frequently than in women with functional bowel disease. One of the causes of
      reproductive disorders in patients with HC might be malabsorption disorders of
      essential nutrients in the small intestine. The presence of reproductive
      disorders should be considered as a risk factor for celiac disease, so these
      women should be screened for celiac disease.

PMID- 22364011
TI  - [Recommendations of the Russian Scientific Society of Gastroenterologists on the
      diagnostics and treatment of chronic pancreatitis (adopted at the 11th Congress
      of the RSSG, March 2, 2011, at the meeting of Russian Pancreatic Club)].

PMID- 22364012
TI  - [43rd Congress of the European Pancreatic Club].

PMID- 22364014
TI  - [Information on the XI East Siberian Gastroenterological Conference with
      international participation "Clinical-Epidemiological and Ethnological
      Environmental Issues of Digestive System Diseases"].

PMID- 22364013
TI  - [All Russian National Conference on "Kazan School of Therapists" 'dedicated to
      235th anniversary of M Ia Mudrov].

PMID- 22364015
TI  - [Report on conference "Prophylaxis and Rehabilitation of Digestive System
      Diseases" in Kislovodsk].

PMID- 22364016
TI  - [Role of PARP and protein poly-ADP-ribosylation process in regulation of cell
      functions].
AB  - This review focuses on the biological role of enzymes involved in
      posttranslational modification of proteins by their poly-ADP-ribosylation, a NAD
      consuming process with an emerging key role in providing fundamental cell
      functions. To this end, detailed analysis of structural organization in relation
      to basic functions of the poly(ADP-ribose) polymerase-1 (PARP-1), the founding
      member of the PARP family, and other poly(ADP-ribose) polymerase isoforms is
      presented here. These include the current views on the role of PARP family
      enzymes and processes of poly-ADP-ribosylation of proteins in chromatin structure
      remodeling, DNA damage repair, regulation of gene expression, and integration of
      cellular signaling pathways. Considerable attention is paid to the involvement of
      PARP in cellular functions, particularly in cell division, intracellular
      transport of macromolcules, proteasomal protein degradation, immune response and
      caspase-independent necrotic pathways defined as necroptosis (programmed
      necrosis). In the light of the remarkable successes that have been reported for
      treating inflammatory disorders and cancer with different classes of PARPs
      inhibitors, we discuss the prospects of targeting PARPs with therapeutic
      purposes.

PMID- 22364017
TI  - [Role of charge and hydrophobic effects in reactions of peptide substrates and
      inhibitors with thrombin].
AB  - A substrate and inhibitor analysis of the thrombin interaction with synthetic
      peptide substrates and inhibitors of differing hydrophobicity and volume of the
      side amino acid residue, localized in the sub-centers thrombin S2 and S3 were
      carried out. The kinetic parameters of individual stages of the enzymatic
      reaction process (K(S), k2, k3) were estimated. It is shown that the efficiency
      of acylation and deacylation stages of the enzymatic reaction decreases with
      increasing hydrophobicity of the substituent in P2 as well as P3, at the same
      time the affinity of selected peptides toward enzyme is steadily increasing. With
      the aim to evaluate the hydrophobicity of compounds a LogP value was calculated
      and was made an attempt to compare them with the correspondent Ki values.
      Comparative kinetic analysis of Z-Arg-OMe and its uncharged analogue Z-Cit-OMe
      has shown the absence of uncharged analog hydrolysis, however, the mentioned
      citrulline derivate inhibits the hydrolysis of the charged analogue. These
      findings confirm the important role of hydrophobic moiety in the structure of
      thrombin inhibitors in preferential binding mode and inhibition of thrombin
      active side.

PMID- 22364018
TI  - The effect of permeability transition pore opening on reactive oxygen species
      production in rat brain mitochondria.
AB  - The influence of mitochondrial permeability transition pore (MPTP) opening on
      reactive oxygen species (ROS) production in the rat brain mitochondria was
      studied. It was shown that ROS production is regulated differently by the rate of
      oxygen consumption and membrane potential, dependent on steady-state or non
      equilibrium conditions. Under steady-state conditions, at constant rate of Ca2+
      cycling and oxygen consumption, ROS production is potential-dependent and
      decreases with the inhibition of respiration and mitochondrial depolarization.
      The constant rate of ROS release is in accord with proportional dependence of the
      rate of ROS formation on that of oxygen consumption. On the contrary, transition
      to non-equilibrium state, due to the release of cytochrome c from mitochondria
      and progressive respiration inhibition, results in the loss of proportionality in
      the rate of ROS production on the rate of respiration and an exponential rise of
      ROS production with time, independent of membrane potential. Independent of
      steady-state or non-equilibrium conditions, the rate of ROS formation is
      controlled by the rate of potential-dependent uptake of Ca2+ which is the rate
      limiting step in ROS production. It was shown that MPTP opening differently
      regulates ROS production, dependent on Ca2+ concentration. At low calcium MPTP
      opening results in the decrease in ROS production because of partial
      mitochondrial depolarization, in spite of sustained increase in oxygen
      consumption rate by a cyclosporine A-sensitive component due to simultaneous work
      of Ca2+-uniporter and MPTP as Ca2+-influx and efflux pathways. The effect of MPTP
      opening at low Ca2+ concentrations is similar to that of Ca2+-ionophore, A-23187.
      At high calcium MPTP opening results in the increase of ROS release due to the
      rapid transition to non-equilibrium state because of cytochrome c loss and
      progressive gating of electron flow in respiratory chain. Thus, under
      physiological conditions MPTP opening at low intracellular calcium could
      attenuate oxidative damage and the impairment of neuronal functions by
      diminishing ROS formation in mitochondria.

PMID- 22364019
TI  - [Transmembrane Ca2+ exchange in depolarized rat myometrium mitochondria].
AB  - Polarization of the inner membrane is the key factor in maintenance of the
      physiologically significant cations accumulation, in particular Ca2+, in the
      mitochondria. It has been well established that mitochondria accumulate calcium
      through the uniporter, driven by the mitochondrial membrane potential.
      Nevertheless, it has been shown that depolarized mitochondria also accumulate
      Ca2+. The aim of this paper is to investigate free Ca level in depolarized
      myometrium mitochondria. As we have shown previously Ca2+ addition to the
      incubation medium, that did not contain K-phosphate, ATP and Mg2+, led to inner
      mitochondrial membrane depolarization. Nevertheless Ca2+ addition to such medium
      led to the concentration-dependent accumulation of this cation in the matrix. RuR
      or Mg addition to the incubation medium led to the higher elevation of
      mitochondrial Ca2+ level in depolarized mitochondria. Mitochondrial Ca2+ level
      was not affected by 5 microM cyclosporine A. It was suggested that H+/Ca2+
      exchanger could provide calcium accumulation in depolarized mitochondria. The
      elevation of mitochondrial Ca2+ level after addition of Mg2+ and RuR may be due
      to inhibition of Ca2+- efflux through Ca2+ uniporter.

PMID- 22364020
TI  - [Function of transport H+-ATPases in plant cell plasma and vacuolar membranes of
      maize under salt stress conditions and effect of adaptogenic preparations].
AB  - Participations of electrogenic H+-pumps of plasma and vacuolar membranes
      represented by E1-E2 and V-type H+-ATPases in plant cell adaptation to salt
      stress conditions has been studied by determination of their transport
      activities. Experiments were carried out on corn seedlings exposed during 1 or 10
      days at 0.1 M NaCl. Preparations Methyure and Ivine were used by seed soaking at
      10(-7) M. Plasma and vacuolar membrane fractions were isolated from corn seedling
      roots. In variants without NaCl a hydrolytical activity of plasma membrane H+
      ATPase was increased with seedling age and its transport one was changed
      insignificantly, wherease the response of the weaker vacuolar H+-ATPase was
      opposite. NaCl exposition decreased hydrolytical activities of both H+-ATPases
      and increased their transport ones. These results demonstrated amplification of
      H+-pumps function especially represented by vacuolar H+-ATPase. Both
      preparations, Methyure mainly, caused a further increase of transport activity
      which was more expressed in NaCl variants. Obtained results showed the important
      role of these H+-pumps in plant adaptation under salt stress conditions realized
      by energetical maintenance of the secondary active Na+/H+ -antiporters which
      remove Na+ from cytoplasm.

PMID- 22364021
TI  - Effect of sodium nitroprusside and S-nitrosoglutathione on pigment content and
      antioxidant system of tocopherol-deficient plants of Arabidopsis thaliana.
AB  - Sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) were used as a source
      of exogenous nitric oxide (NO) to investigate their effects on biochemical
      parameters and antioxidant enzyme response in leaves of wild type Columbia and
      tocopherol-deficient vte4 and vte1 mutant lines of Arabidopsis thaliana plants
      and possible tocopherol involvement in regulation of antioxidant response under
      NO-induced stress. SNP enhanced the activity of the enzymes, that scavenge
      hydrogen peroxide in leaves of all studied lines, and increased glutathione
      reductase and glutathione-S-transferase activity there. In addition, it decreased
      the intensity of lipid peroxidation in vte1 mutant line leaves. At the same time,
      GSNO increased the levels of protein carbonyls and inactivated enzymes ascorbate
      peroxidase, guaiacol peroxidase and dehydroascorbate reductase in almost all
      investigated plant lines. In contrast to wild type, GSNO increased superoxide
      dismutase activity and decreased catalase activity and chlorophyll a/b ratio in
      the leaves of two mutant lines. It can be assumed that tocopherols in some way
      are responsible for plant protection against NO-induced stress. However the
      mechanisms of this protection remain unknown.

PMID- 22364022
TI  - [Influence of variuos ultrasound regimens on oxide-modified actomyosin
      superprecipitation reaction from skeletal muscle of rabbit].
AB  - A comparative study of rabbit skeletal muscles oxide-modified actomyosin
      superprecipitation reaction in dependence on continuous and impulsive (2 ms)
      ultrasound regimens was studied. From the analyses of kinetic curves the effect
      of the value of superprecipitation (A(m) - A(0)), time t1/2, required for
      achievement of half of its value was determined, and the normalized maximal rate
      of this reaction V was also calculated. It is shown that the use of continuous
      ultrasound to oxide-modified actomyosin was associated with a significant
      decrease of superprecipitation relative to controls. However, pulsed ultrasound
      caused a significant increase in superprecipitation value except for the values
      (A(m) - A(0)) in the application of the intensity of 0.2 W/cm2. The oxide
      modified actomyosin superprecipitation value under the effect of continuous and
      impulsive ultrasound at intensity 1 W/cm2 in relative to control and all other
      applied intensities decrease to the most extent. It is caused perhaps by thermal
      influence of ultrasound. In general, the data obtained give reason to assume that
      the effects of continuous and pulsed ultrasound on the reaction of oxide-modified
      proteins complex superpretsipitatsii identical.

PMID- 22364023
TI  - [Antioxidative effect of the N-stearoylethanolamine in the heart tissue and blood
      plasma of rats under doxorubicin treatment].
AB  - The influence of N-stearoylethanolamine on the alterated antioxidant enzyme
      activity in the heart tissue and blood plasma of rats under the doxorubicin
      treatment was investigated. It was shown that doxorubicin administration caused
      the decrease of antioxidant enzymes activity (superoxide dismutase and
      glutathione peroxidase) in the heart tissue. Administration of the NSE promoted
      the partial normalization of these enzymes activity. It was shown that
      doxorubicin treatment caused the increase of the urea and creatinine level in the
      blood plasma of experimental animals. The NSE administration normalized the level
      of the urea and did not affect creatinine level.

PMID- 22364024
TI  - [Metal-binding functions and antioxidant properties in human thyroid gland under
      iodine deficient nodular colloidal goiter].
AB  - Copper and zinc levels in the tissue of thyroid gland (TG) and their metal
      binding proteins metallothioneins (MT) as well as state of the antioxidant system
      in persons that had no thyroid disease and patients with endemic iodine
      deficiency nodular colloidal goiter has been investigated. In the patients with
      thyroid disease, oxidative damage was indicated despite elevated levels of MT-SH
      and glutathione, and elevated copper and decreased zinc concentration in TG
      tissue. MTs partly bound the excess of copper but its concentration in the
      unbound to MT form was two-fold compared to the control value.

PMID- 22364025
TI  - [Biochemical features of cancer cachexia under conditions of different provision
      with vitamin A].
AB  - On the model of tumor growth of Guerin's carcinoma and experimental modeling of
      vitamin A provision the biochemical characteristics of tumor cachexia in animals
      with malignant tumors and different vitamin A provision status were studied. It
      is determined that tumor growth in the body, deprived of vitamin A, is
      characterized by negative nitrogen balance, decrease of glucose, free fatty acids
      and ketone bodies level in the blood serum, which indicates the increase of
      cancer cachexia.

PMID- 22364026
TI  - Glutathione level of Desulfovibrio desulfuricans IMV K-6 under the influence of
      heavy metal salts.
AB  - Glutathione is the metal stress protector and changes of its level in the sulfate
      reducing bacteria cells under the influence of heavy metal salts have not been
      studied yet. CdCl2, Pb(NO3)2, CuCl2, and ZnCl2 influence on the total glutathione
      level in cell-free extracts of sulfate-reducing bacteria Desulfovibrio
      desulfuricans IMV K-6 was studied. The research has been carried out using
      Ellman, Lowry methods, statistical processing of the results. It was shown that
      the glutathione level depends on the heavy metal salts concentration in the
      medium. The total glutathione level was the highest under the influence of
      Pb(NO3)2. Other salts were also toxic to bacteria because glutathione level
      increased in bacterial cells after addition of these salts to the medium. On the
      basis of the results of our work the range of heavy metal salts influence on D.
      desulfuricans IMV K-6 cells glutathione level has been formed for the first time:
      Pb(NO3)2 > CuCl2 > CdCl2 > ZnCl2.

PMID- 22364027
TI  - [Method for endogenous formaldehyde evaluation in animal organism].
AB  - A method for endogenous formaldehyde (FA) level evaluation has been worked out.
      The method involves the administration of dimedone, which forms the stable
      complex with FA, and the determination of formaldimedone concentration in
      biological samples by the fluorescence approach. The method was tested on rat's
      models of FA metabolism modulation. Animals received FA (10 mg/kg); or
      methylamine - substrate of FA-generating enzyme SSAO, (250 mg/kg); or
      semicarbazide - SSAO inhibitor, (200 mg/kg). Concentration of FA bound with
      dimedone in the liver tissue were, correspondingly: 7.5 +/- 1.5 mkg/kg; 5.4 +/-
      0.9 mkg/kg; 2.4 +/- 0.7 mkg/kg; control - 4.2 +/- 1.4 mkg/kg. Obtained data
      indicate, that the elaborated method gives reliable information about FA level.

PMID- 22364028
TI  - [Investigation of proteins of nerve tissue and their metabolism at the Palladin
      Institute of Biochemistry of NAS of Ukraine (1972-1990)].

PMID- 22364030
TI  - [The Nobel Prize in physiology and medicine of 2011].

PMID- 22364029
TI  - [Information provision of scientific researches by the library Palladin Institute
      of Biochemical of NAS of Ukraine].

PMID- 22364031
TI  - [Instituto Nacional de Rehabilitacion].

PMID- 22364032
TI  - [Clinical trial on the effect of buphenine, aminophenazone and diphenylpyraline
      hydrochloride in treating the common cold in children of 6 to 24 months of age].
AB  - INTRODUCTION: Acute respiratory infections are the second leading cause of
      morbidity in children under 18 years. Several drugs have been used with variable
      efficacy and safety, trying to reduce the associated symptoms and improve quality
      of life. OBJECTIVE: To evaluate the efficacy and safety of buphenine,
      aminophenazone and diphenylpyraline hydrochloride when compared with placebo for
      the control of symptoms associated with common cold in children 6-24 months of
      age. MATERIAL AND METHODS: Randomized clinical trial, double blind, placebo
      controlled, in 100 children < 24 months of any gender, with symptoms associated
      to common cold. They received the drug under study vs. placebo for seven days.
      Both groups received acetaminophen. The change on common cold related symptoms
      were evaluated. Statistic analysis was made with STATA 11.0 for Mac. RESULTS:
      Fifty-three children were randomized to study drug and forty-seven to placebo.
      Age of children in each group was similar (12.2 +/- 5.8 months vs. 12.7 +/- 5.8
      months, p NS). There were significant differences between groups in relation to
      rhinorrea and sneezing resolution, with better results in Flumil group and no
      adverse events observed. CONCLUSIONS: The results in this study indicates that
      Flumil is a safe and effective drug for control of symptoms present in the common
      cold in children aged 6-24 months.

PMID- 22364033
TI  - [Medical and surgical health care for congenital heart disease: a panoramic
      vision of the reality in Mexico. Inquiry 2009].
AB  - INTRODUCTION: The only way to characterize the Mexican problem related to
      congenital heart disease care is promoting the creation of a national database
      for registering the organization, resources, and related activities. MATERIAL AND
      METHODS: The Health Secretary of Mexico adopted a Spanish registration model to
      design a survey for obtaining a national Mexican reference in congenital heart
      disease. This survey was distributed to all directors of medical and/or surgical
      health care centers for congenital heart disease in Mexico. This communication
      presents the results obtained in relation to organization, resources and
      activities performed during the last year 2009. RESULTS: From the 22 health care
      centers which answered the survey 10 were reference centers (45%) and 12 were
      assistant centers (55%). All of them are provided with cardiologic auxiliary
      diagnostic methods. Except one, all centers have at least one bidimentional
      echocardiography apparatus. There is a general deficit between material and human
      resources detected in our study. Therapeutic actions for congenital heart disease
      (70% surgical and 30% therapeutical interventionism) show a clear centralization
      tendency for this kind of health care in Mexico City, Monterrey and finally
      Guadalajara. CONCLUSIONS: Due to the participation of almost all cardiac health
      centers in Mexico, our study provides an important information related to
      organization, resources, and medical and/or surgical activities for congenital
      heart disease. The data presented not only show Mexican reality, but allows us to
      identify better the national problematic for establishing priorities and propose
      solution alternatives.

PMID- 22364034
TI  - [Dermatoses in patients with acute myeloid and lymphoid leukemia. Cohort follow
      up in a tertiary care hospital].
AB  - INTRODUCTION: Cutaneous manifestations in patients with acute leukemia (AL) cover
      a broad spectrum, including those due to leukemia per se, to chemotherapy and
      other drugs and those inherent to hospital care. MATERIAL AND METHODS: This is a
      cohort study in a tertiary hospital setting where the development of dermatoses
      was followed for 2 years in 22 patients with the diagnosis of AL. RESULTS: During
      the study, all patients developed some type of dermatosis, mostly due to
      chemotherapy.

PMID- 22364035
TI  - Bell's palsy. A prospective, longitudinal, descriptive, and observational
      analysis of prognosis factors for recovery in Mexican patients.
AB  - OBJECTIVE: To determine the prognosis factors in Mexican patients with Bell's
      palsy. MATERIAL AND METHODS:  DESIGN: We designed a prospective, longitudinal,
      descriptive, and observational analysis. Two hundred and fifty one patients
      diagnosed with Bell's palsy at the National Institute of Rehabilitation were
      included. We studied the sociodemographic characteristics, seasonal occurrence,
      sidedness, symptoms, and therapeutic options to determine the prognostic factors
      for their recovery. RESULTS: Thirty-nine percent of patients had a complete
      recovery and 41.5% had an incomplete recovery. Marital status, gender, etiology,
      symptoms, sidedness, House-Brackmann grade, and treatments did not represent
      significant prognostic factors for recovery. Age > 40 years (OR = 2.4, IC 95% 1.3
      4.3, p = 0.002) and lack of physical therapy (OR = 6.4, IC 95% 1.4-29.6, p =
      0.006) were significant prognostic factors for incomplete recovery. Familial
      palsy resulted to be a protective prognostic factor against an incomplete
      recovery (OR = 0.54, IC 95% 0.28-1.01, p = 0.039). This protection factor was
      only significant in female patients (OR = 0.41, p = 0.22) but not in male
      patients (OR = 1.0, p = 0.61). CONCLUSIONS: The proportion of cases with
      incomplete recovery was high. The age > 40 years and lack of physical therapy
      were the only significant prognostic factors for an incomplete recovery.

PMID- 22364036
TI  - Extended major histocompatibility complex haplotypes, ancestry and acute kidney
      transplant rejection in Mexicans.
AB  - INTRODUCTION: Extended major histocompatibility complex (MHC) haplotypes are
      associated with several autoimmune diseases, and these appear to depend on
      ancestry. OBJECTIVE: To evaluate the association of extended MHC gene
      frequencies, ancestry, and acute rejection. MATERIAL AND METHODS: 127 living
      kidney transplant recipients who underwent kidney transplantation in Mexico City
      between January 2004 and October 2007 with follow up until October 2008. The
      primary outcome was biopsy proven acute rejection. Ancestry was considered as
      either Amerindian or admixtures with Caucasian, African or Oriental genes. Allele
      and haplotype frequencies were estimated for HLA A, B and DR loci. Hardy Weinberg
      (HW) and delta values were analyzed to test for linkage disequilibrium (LD).
      RESULTS: There were no significant differences in the baseline characteristics
      between groups. 50% were men, and 28, 61 and 10% of the patients shared zero, one
      or two haplotypes, respectively. The whole population was Hispanic and born in
      Mexico. Median PRA was 0%. Allelic variance in all MCH loci was in HW
      equilibrium, 14% developed acute rejection. There was a high frequency of
      Amerindian haplotypes; admixture genes and LD were higher in the group with acute
      rejection. When compared to the group without acute rejection, the haplotype
      A1*B8*DR3 was more frequent in donors in whom their recipients had acute
      rejection (p = 0.008), while A28*B39*DR4 was more common in the recipients with
      acute rejection (p = 0.003). Multivariate Cox regression models did not attenuate
      these associations. CONCLUSIONS: Ancestry and LD may be associated with risk of
      acute rejection and may therefore be useful in directing immunosuppression.

PMID- 22364037
TI  - [Self-care ability in the hypertensive patient control].
AB  - MATERIAL AND METHODS: Trough an analytical cross-sectional study the association
      of self-care ability and the blood pressure control was evaluated. We studied
      controlled and uncontrolled hypertensive patients, both groups with 79 subjects.
      Self-care basic conditioning factors and capacities scale in patients with
      hypertension was used. RESULTS: Self-care ability was good in 73.4% of controlled
      and in 3.8% of the uncontrolled patients (p < 0.05). The 91.2% of controlled and
      67.9% of uncontrolled presented a positive family system (p < 0.05). Socio
      cultural factors were good in 64.6% of controlled against 16.7% of the
      uncontrolled (p < 0.05). Environmental factors were good in 50.6% of controlled
      and 2.6% of the uncontrolled (p < 0.05). CONCLUSION: According to these results
      we conclude that there is association between self-care ability and control of
      hypertension.

PMID- 22364038
TI  - [Neuropsychiatric symptoms in older adults with and without dementia in urban and
      rural regions. Results of the 10/66 Dementia Research Group in Mexico].
AB  - OBJECTIVE: To describe, in a Mexican sample of urban and rural residents older
      than 65 years, with and without dementia, the frequency and severity of
      neuropsychiatric symptoms. MATERIAL AND METHODS: This work is part of the multi
      center, epidemiological study carried out by the 10/66 Dementia Research Group,
      with 1,003 subjects from an urban region and 1,000 subjects from a rural region.
      Neuropsychiatric symptoms were assessed with the abbreviated version of the
      Neuropsychiatric Inventory (NPI-Q). RESULTS: Eighty six and eighty five dementia
      cases were found in the urban and rural regions, respectively. Subjects with
      dementia were more frequently widows, older and less educated, and the ones from
      the rural region had fewer neuropsychiatric symptoms, compared to the urban
      region. In both regions all symptoms were more severe in subjects with dementia.
      A high frequency of affective symptoms (depression and apathy specially) was
      observed, and irritability and anxiety in second term. The caregiver stress
      levels were associated with the frequency and severity of symptoms. CONCLUSIONS:
      This is the first study reporting neuropsychiatric symptoms associated with
      dementia identified by means of culturally validated and population based
      diagnostic criteria, in Mexican residents of urban and rural settings.

PMID- 22364039
TI  - [Immunization with monovalent oral vaccine against rotavirus in Mexico.
      Evaluation of the data of two years of the system of temporarily adverse event
      reports associated to vaccination (ETAV)].
AB  - BACKGROUND: The gastrointestinal manifestations are the adverse events mainly
      studied to the application of the vaccine against rotavirus. MATERIAL AND
      METHODS: In order subsequent to consider the risk of associated events taken care
      of the vaccination against rotavirus in infants, we realized a retrospective
      study of 2 years, evaluating 7,691,757 distributed doses of oral vaccine, in 2008
      and 2009. RESULTS: The risk considered of an event associated after the
      application of the oral vaccine against rotavirus is of 2.9 events by 1,000,000
      distributed doses. CONCLUSIONS: The taken care of associated events were little
      common subsequent to the vaccination against rotavirus.

PMID- 22364040
TI  - [New microsurgical model for the study of the morphological adaptative response
      of venous grafts].
AB  - INTRODUCTION: Animal models have been developed for the study of the intimal
      hyperplasia, a common cause of venous graft stenosis. OBJECTIVE: To establish a
      venous graft animal model for the study of the morphologic adaptative response to
      the arterial circulation. MATERIAL AND METHODS: A venous graft was placed in the
      arterial circulation of the caudal extremity from Wistar rats. In order to
      develop the model, it was carried out a morphologic study of the caudal extremity
      blood vessels. Three possible sites were evaluated for the obtaining of the
      venous graft. RESULTS: Graft permeability and viability were observed only in one
      segment, between the muscular branches and the origin of the saphenous vein. The
      portion of vein that was obtained from one extremity, was placed in the arterial
      circulation of the opposite extremity. CONCLUSIONS: A venous graft animal model
      was established, using a femoral vein segment, between the muscular branches and
      the origin of the saphenous vein, placing it in the homonyme artery of the
      opposite extremity.

PMID- 22364041
TI  - NFE2L2 gene variants and susceptibility to childhood-onset asthma.
AB  - INTRODUCTION: Environmental factors causing oxidative stress are known to be
      associated with asthma morbidity. The antioxidative gene NFE2L2 has been
      implicated in asthma development in mice models. In humans, the SNPs -617C/A and 
      653G/A, located at the promoter region of NFE2L2 gene, have been found associated
      with the susceptibility to develop diverse chronic-degenerative diseases.
      OBJECTIVE: To determine if there is association of the -617C/A and -653G/A NFE2L2
      SNPs and childhood-onset asthma in a Mexican population. MATERIALS AND METHODS:
      In a case-control study 242 unrelated patients with diagnosis of asthma and 358
      ethnically- and sex-matched healthy individuals were included. The -617C/A and 
      653G/A NFE2L2 genotyping was carried out using the TaqMan allelic discrimination
      assay. RESULTS: The risk allele of both polymorphisms showed a high frequency in
      our sample (-617A: 24% and -653A: 40%), similarly to those previously reported in
      Asiatic populations (-617A: 24-29% and -653A: 42-52%; p > 0.05). In contrast, the
      -617A allele frequency was higher than that reported in a European-African
      admixed population (10%, p < 0.001). The allelic and genotypic frequencies from
      both polymorphisms showed no significant differences among cases and controls in
      female and male samples. Likewise, haplotype analysis found no association
      between NFE2L2 gene variants and the disease. CONCLUSIONS: Despite the
      experimental evidence suggesting that NFE2L2 gene is involved in asthma
      pathogenesis, the -617C/A and -653G/A SNPs were not associated with childhood
      onset asthma.

PMID- 22364042
TI  - [Critical reading of reports of educational research in teachers of IMSS.
      Multicenter study].
AB  - AIM: To determine the effect of an educational strategy promoting participation
      in the development of critical reading of educational research reports on
      professors of Educational Research and Teacher Education (CIEFD's). MATERIAL AND
      METHODS: We performed an intervention study, multicenter professors (medical
      specialists) who enrolled in the courses: Diploma in teaching methodological
      level 1 and 2 (n = 46, n = 29, respectively) in the six CIEFD's (D.F. Siglo XXI,
      DF. La Raza, Nuevo Leon, Sonora, Puebla and Jalisco), in the period March to
      August 2007. A tool was built that assessed the variables critical appraisal of
      educational research reports, the construct validity, content and reliability was
      assessed by experts in education research. The educational strategy developed in
      the form of seminars, which were held three times a week in the Certification in
      teaching methodological level 1 and twice per week in the Certification Level 2
      in teaching methodology duration per session: 6 h. The instrument was applied at
      the beginning and end of the course. RESULTS: In the two Graduates it was
      observed in the total group, an advance in the three indicators of critical
      reading, which was expressed with statistically significant differences; in the
      global score of the Diploma level 1 (final vs. initial measurement) the following
      mediums were observed: 36-67 (p = 0.0001); in the Diploma level 2, it was
      observed in its overall rating: 42-78 (p = 0.0001). DISCUSSION: This inquiry from
      the results observed some of theoretical approaches to mainstreaming
      participatory. CONCLUSION: An educational strategy promoting participation
      produced a breakthrough in the three indicators (to interpret, to judge and to
      formulate proposals) for critical reading of educational research reports.

PMID- 22364043
TI  - [Update in surgical treatment of articular cartilage lesions].

PMID- 22364044
TI  - Prenatal diagnosis in a cystic fibrosis family: a combined molecular strategy for
      a precise diagnosis.
AB  - INTRODUCTION: The high genetic heterogeneity in populations with a wide spectrum
      of mutations in the CF transmembrane conductance regulator gene (CFTR), makes the
      detection of mutations a very hard and difficult task, thereby limiting the
      accurate diagnosis of the disease, mainly in patients with uncharacterized
      mutations. MATERIAL AND METHODS: Molecular strategies, like targeted
      identification of the most frequent CFTR mutations in Mexican population combined
      with linkage analysis using markers, is very useful for carrier detection and for
      prenatal diagnosis in affected families with CF. In this paper we show that the
      combination of methodologies was a crucial alternative to reach a precise
      prenatal CF diagnosis. We documented CF diagnosis in a 14th-week fetus combining
      the screening of the most common mutations in Mexican population with linkage
      analysis of two extragenic polymorphisms (XV2C/TaqI and KM19/PstI). RESULTS: We
      determined that the fetus inherited the PG542X mutation from its mother and an
      unknown mutation from its father through the chromosomal phases analysis.

PMID- 22364045
TI  - Achieving health equity.

PMID- 22364046
TI  - The strategic impact of a changing curriculum and learning environment on medical
      students' academic performance.
AB  - In recent years, the administration of Meharry Medical College, School of
      Medicine (SOM), Nashville, Tennessee, recognized the need to modify the
      curriculum to help improve student academic performance especially on the
      National Board of Medical Examiners (NBME) US Medical Licensing Examination
      (USMLE) steps 1 and 2. Thus, a number of changes occurred with respect to the
      traditional curriculum in the SOM, resulting in an integrated organ system-based
      curriculum design. The change in the learning environment was studied to
      determine the impact on performance after the introduction of the integrated
      organ system-based curriculum as compared to that of the traditional curriculum.
      With the utilization of a cadre of variables, it was believed that the strategic
      impact anticipated would provide a predictive validity profile to assist in the
      identification of students "at risk" of failure so that proactive intervention
      methodology could be made available to facilitate the students' successful
      progression during matriculation in the SOM. The purpose of this study was to
      analyze whether students trained with the integrated organ systems curriculum
      perform better than students trained with the traditional medical school
      curriculum on the medical education preclinical subject board examinations, and
      the NBME USMLE steps 1 and 2 examinations. From the 584 students studied in the
      control group (graduation classes for years 2005, 2006, and 2007) and the
      intervention group (graduation classes for years 2008, 2009, and 2010),
      significant improvement in performance on the NBME USMLE steps 1 and 2
      examinations was noted following the introduction of the integrated organ system
      based curriculum particularly among "at-risk" students. Data access availability
      from the School of Medicine of Meharry Medical College automatically gave reason
      for a preferential comparative relationship and study of the resulting strategic
      impact on cohorts graduating in years 2005-2010. Thus, this longitudinal
      retrospective review was to determine whether or not students' academic
      performance profiles might provide some valid predictive information to help
      identify "at-risk" students early in their pursuit of a health professions
      career.

PMID- 22364047
TI  - A writing group for female assistant professors.
AB  - INTRODUCTION: The number of female medical school faculty being promoted and the
      speed at which they are promoted have not kept pace with their male counterparts
      at many institutions. One of the reasons is that these women are not publishing
      peer reviewed manuscripts at an equivalent rate. This study evaluates the impact
      of a women's writing group on faculty publication rates. MATERIALS AND METHODS:
      The writing group was conducted by 2 senior faculty members at the University of
      Pennsylvania School of Medicine and targeted female junior faculty. The writing
      group consisted of a didactic skills curriculum, question sessions, and both
      faculty and peer support to improve publishing rates. Curriculum vitae were
      collected, and PubMed and Ovid searches were used to establish the publishing
      productivity of the writing group participants both before and after
      participation in the writing group. RESULTS: On average, women who completed the
      writing group showed a nearly 3-fold increase in average publishing rate from 1.5
      papers per year preceding the course to 4.5 per year following completion of the
      writing group (p<.001). CONCLUSIONS: The results from our program suggest that a
      women's writing group is an effective intervention for increasing publishing
      rates of female junior faculty. In addition to the documented improvement in
      publication rates, we watched participants develop clearer writing styles, lose
      many of their inhibitions about writing, respond to group affiliation and
      collaboration, and gain tremendous self-confidence.

PMID- 22364048
TI  - A conceptual model for faculty development in academic medicine: the
      underrepresented minority faculty experience.
AB  - In May 2010, the Association of American Medical Colleges reported that nonwhite
      professors have a lower promotion rate than white professors. A cohort of 30
      underrepresented minority (URM) junior faculty who participated in a structured
      faculty development program at a public, research-intensive, academic medical
      center were followed in a 10-year longitudinal study. This paper reports on the
      career status of 12 of the 30 URM faculty who were eligible for promotion during
      this period. Ninety-two percent (11/12) of URM faculty eligible for promotion
      were promoted to associate professor. When asked what factors contributed to
      their success, these URM faculty identified access and support of senior faculty
      mentors, peer networking, professional skill development, and knowledge of
      institutional culture. A faculty development program that addresses these
      components can promote the success of URM faculty in academic medicine.

PMID- 22364049
TI  - Student's perspective of success in a postbaccalaureate program.
AB  - OBJECTIVE: To identify contributors to the success of students in medical school
      that graduate from a 1-year postbaccalaureate bridge program. METHOD: In 2010,
      using rigorous qualitative methodology, the principal investigator interviewed a
      random sample of 15 (23%) of current and past graduates of The Florida State
      University College of Medicine Bridge program. The investigators recorded and
      transcribed the interviews, utilized consensual qualitative research methodology
      to analyze the data, and identified an overarching theoretical construct.
      RESULTS: Content analysis of all 15 interviews yielded 73 themes, which were
      grouped into 6 broad categories/domains: The Florida State University College of
      Medicine Bridge Program attributes, personal attributes, proof of competence,
      support systems, exposure to medical programs, and faith/religion. CONCLUSION:
      Postbaccalaureate programs prepare students for success in medical school. The
      Florida State University College of Medicine Bridge Program has been particularly
      successful in identifying and educating students who demonstrated promise upon
      application, despite noncompetitive grades and Medical College Admission Test
      scores. The authors identify the characteristics and individual experiences of
      the students and program that relate to success.

PMID- 22364050
TI  - Introduction to the medical professions through an innovative medical student-run
      pipeline program.
AB  - Underrepresented minorities (URMs) make up a disproportionately small percentage
      of medical school applicants, matriculants, and physicians relative to the
      general US population. Preprofessional pipeline programs may help introduce URMs
      to careers in the medical field. MiniMeds was developed as a paracurricular
      enrichment program that targeted URM students. The curriculum was designed and
      administered by medical students, and 2 trials of this program were conducted.
      Data were collected pre and post program through a survey that assessed knowledge
      of medical concepts and knowledge of and interest in careers in medicine.
      Attendance at program sessions correlated with baseline knowledge about medical
      professions. Knowledge about medical concepts increased significantly from
      baseline to follow-up for boys, a group significantly represented by URMs in our
      cohort. Median scores for knowledge of medical careers increased significantly
      from baseline to followup for URMs as well as for boys and girls. Preprofessional
      pipeline programs such as MiniMeds are able to engage and develop medical
      knowledge in URM students at a critical developmental age. Further evaluation and
      implementation of programs that incorporate medical students to actively develop
      and lead pipeline programs are warranted.

PMID- 22364051
TI  - Lessons learned from community-based minority health care serving system
      participation in an NIH clinical trial.
AB  - To address the historically low rate of minority participation in clinical
      trials, the NIH and others have provided incentives to increase the diversity of
      patients and study sites involved in NIH-funded research. An example of the
      efforts to achieve this aim was the creation of the Partnerships Program to
      Reduce Cardiovascular Health Disparities," whereby a health care system that
      serves a predominantly minority patient population partners with a research
      intensive medical center that has a track record of NIH-supported research. In
      the city of Baltimore, Maryland, the Bon Secours Baltimore Health System
      partnered with the University of Maryland and was awarded 1 of 7 U01 partnerships
      within cardiovascular health. This commentary describes the qualitative
      experiences of the participating physicians and not a quantitative analysis of
      the study data or findings. It describes the lessons learned by Bon Secours that
      can address patient and physician barriers to clinical trial participation. Based
      upon the views of participating physicians, it is easiest to engage physicians
      when there is a supportive principal investigator and appropriate infrastructure
      to do research. Patient recruitment requires cultural competence and sensitivity,
      and using minority physicians, nurses, and staff may greatly assist in building
      the trust that is necessary for patients to be willing to participate in
      research. Clarity of the study's purpose and aims at the outset is critical, and
      reinforcement with educational sessions helped with physician and patient
      retention throughout the study.

PMID- 22364052
TI  - Exploring differences in trust in doctors among African American men and women.
AB  - OBJECTIVES: Low trust in doctors may partially account for African Americans'
      adverse health outcomes. Understanding the drivers of low trust can guide health
      care policy to improve trust and delivery of health care for African Americans.
      This study examines gender differences in trust in doctors among African
      Americans and explores factors differentially associated with low level trust for
      men vs women. METHODS AND MEASURES: Cross-sectional analysis of 3649 African
      Americans using data from the 2003-2004 Community Tracking Study Household
      Survey, including 4 items measuring trust in doctors (range, 1 = lowest trust and
      5 = highest trust). Items were assessed separately and as an index measure.
      Linear regression analyses adjusted for multiple confounders and accounted for
      complex data sampling. RESULTS: Overall, men were less trusting of doctors than
      women. However, men differed from women only on 2 trust measures: "doctor
      influenced by insurance rules" (adjusted mean scores = 2.48 for men and 2.79 for
      women, p = .001) and "doctor performs unnecessary tests" (adjusted mean score =
      4.00 for men and 4.28 for women, p = .010). Common correlates of low trust in men
      and women included less than high school education, age of at least 65 years, and
      having no usual source of care. Unique correlates of lower trust for men included
      rural living and no doctor visit in the preceding year. Unique correlates for
      women included low income and poorer health status. CONCLUSIONS: There are
      differential predictors of low trust among African American men vs women,
      underscoring the need for gender-based and health care system-level approaches to
      improve African Americans' trust and health outcomes.

PMID- 22364053
TI  - Incomplete follow-up of hemoglobinopathy carriers identified by newborn screening
      despite reporting in electronic medical records.
AB  - OBJECTIVE: Has the recent availability of newborn hemoglobinopathy screening
      results within patient electronic medical records (EMR) of birth hospitals
      facilitated follow-up by primary care pediatric providers? METHODS: An online
      survey of all 137 primary care pediatric providers at a New York City academic
      medical center was conducted in 2008-2009 to assess practices for hemoglobin
      apathy trait follow-up. Physicians were resurveyed 1 year later, following
      educational outreach and a letter of instruction underscoring the availability of
      screening results in the EMR. All 62 primary care pediatricians were surveyed at
      a nearby city hospital for comparison. RESULTS: Overall response rate for the
      initial survey at the teaching hospital was 58% for pediatricians (N = 57) and
      family physicians (N = 23), and 50% for pediatricians at the city hospital (N =
      31). Despite high prevalence of hemoglobinopathies in the population served and
      screening results in EMRs, only 46.2% of providers surveyed at the academic
      center reported routinely checking results of their infant patients: 38.6% of
      pediatricians and 66.7% of family practitioners. Some respondents were unaware
      that results are available in the EMR. The proportion of providers checking
      screening results was not significantly affected by educational intervention (N =
      40). Provision of recommended follow-up for a positive trait result was modestly
      improved, especially in referring families for genetic counseling (25% to 50%,
      p<.01). In contrast, most pediatricians (83%) at the city hospital routinely
      check and perform follow-up. CONCLUSION: Despite access to results in the EMR and
      targeted educational outreach, follow-up of hemoglobinopathy screening by primary
      care varies widely across clinical sites.

PMID- 22364054
TI  - Reliability of Doppler and stethoscope methods of determining systolic blood
      pressures: considerations for calculating an ankle-brachial index.
AB  - PURPOSE: The purposes of this study were to: (1) identify the interrater and
      intrarater reliability of systolic blood pressures using a stethoscope and
      Doppler to determine an ankle-brachial index (ABI), and (2) to determine the
      correlation between the 2 methods. BACKGROUND: Peripheral arterial disease (PAD)
      affects approximately 8 to 12 million people in the United States, and nearly
      half of those with this disease are asymptomatic. Early detection and prompt
      treatment of PAD will improve health outcomes. It is important that clinicians
      perform tests that determine the presence of PAD. METHOD: Two individual raters
      trained in ABI procedure measured the systolic blood pressures of 20 individuals'
      upper and lower extremities. Standard ABI measurement protocols were observed.
      Raters individually recorded the systolic blood pressures of each extremity using
      a stethoscope and a Doppler, for a total of 640 independent measures. RESULTS:
      Interrater reliability of Doppler measurements to determine SBP at the ankle was
      very strong (intraclass correlation coefficient [ICC], 0.93-0.99) compared to
      moderate to strong reliability using a stethoscope (ICC, 0.64-0.87). Agreement
      between the 2 devices to determine SBP was moderate to very weak (ICC, 0.13
      0.61). Comparisons of the use of Doppler and stethoscope to determine ABI showed
      weak to very weak intrarater correlation (ICC, 0.17-0.35). Linear regression
      analysis of the 2 methods to determine ABI showed positive but weak to very weak
      correlations (r2 = .013, P = .184). CONCLUSIONS: A Doppler ultrasound is
      recommended over a stethoscope for accuracy in systolic pressure readings for ABI
      measurements.

PMID- 22364055
TI  - Iron, folate, and vitamin B12 status in the elderly by gender and ethnicity.
AB  - OBJECTIVE: National Health and Nutrition Examination Survey 2001-2002 data were
      used to examine gender and ethnicity relationships to iron, folate, and vitamin
      B12 status, and anemia in 1770 elderly persons. METHODS: Dependent variables
      included dietary intakes and biochemical measures of iron, folate, and vitamin
      B12 status, and hemoglobin. T Tests were performed using SUDAAN software (version
      9.0; Research Triangle Institute International, Research Triangle Park, North
      Carolina). The relationships of gender and ethnicity to adequacy of iron, folate,
      and vitamin B12 status, and anemia were investigated using chi2 tests. RESULTS:
      Males had significantly higher nutrient intakes and better biochemical measures
      of iron status but lower biochemical measures of folate and vitamin B12. Whites
      were significantly more likely to have nutrient intakes higher than those
      recommended by the Food and Nutrition Board. No clear pattern of biochemical
      measures of iron status was seen among the ethnic groups, and there was no
      significant relationship between iron status and ethnicity. Biochemical measures
      of folate status were significantly higher in whites and Mexican Americans than
      in blacks. No significant relationships were found between folate status and
      ethnicity. Mean serum vitamin B12 was significantly higher in blacks than in
      whites and was lowest in other Hispanics who were significantly more likely to be
      vitamin B12 deficient. Blacks had significantly lower mean hemoglobin values than
      whites and were significantly more likely to be anemic. CONCLUSIONS: Based on
      biochemical measures, elderly males are at higher risk of folate and vitamin B12
      deficiencies. Ethnicity was not significantly related to either iron or folate
      status. Other Hispanics were significantly more likely to be vitamin B12
      deficient.

PMID- 22364056
TI  - A qualitative assessment of personal and social responsibility for kidney
      disease: the Increasing Kidney Disease Awareness Network Transplant Project.
AB  - INTRODUCTION: Limited qualitative research has explored opinions of kidney
      disease health care providers regarding racial and ethnic disparities in access
      to and receipt of kidney transplantation. METHODS: Key informant interviews were
      conducted among transplant nephrologists, nephrologists, transplant social
      workers, and transplant coordinators to determine barriers to transplantation
      among African Americans compared to whites with end-stage renal disease (ESRD).
      ANALYSIS: Thirty-eight interviews were audio recorded and transcribed to hardcopy
      for content analysis. Grounded theory was used to determine dominant themes
      within the interviews. Reliability and validity were ensured by several
      coinvestigators independently sorting verbatim responses used for generating
      themes and subsequent explanations. RESULTS: Several major categories arose from
      analysis of the transcripts. Under the category of personal and social
      responsibility for kidney transplantation, interviews revealed 4 major themes:
      negative personal behaviors, acquisition of and lack of self-treatment of
      comorbid conditions, lack of individual responsibility, and the need for more
      social responsibility. Many providers perceived patients as being largely
      responsible for the development of ESRD, while some providers expressed the idea
      that more social responsibility was needed to improve poor health status and
      disparities in kidney transplantation rates. CONCLUSION: Kidney disease health
      providers seemed torn between notions of patients' accountability and social
      responsibility for racial disparities in chronic kidney disease and ESRD. Further
      research is needed to clarify which aspects contribute most to disparities in
      access to transplantation.

PMID- 22364057
TI  - Misperceptions of nicotine replacement therapy within racially and ethnically
      diverse smokers.
AB  - Underuse of evidence-based treatment for smoking cessation, including use of
      nicotine replacement therapy (NRT), is widespread, particularly among minority
      smokers. This paper examines perceptions of NRT among and between racially and
      ethnically diverse groups of smokers. Nine focus groups were held among
      homogenous groups of African American, European American, and Hispanic smokers (N
      = 70). Specific themes included perceptions of: (a) the mechanism by which NRT
      works; (b) NRT development and regulation (ie, purpose and methods of clinical
      trials, Food and Drug Administration oversight, etc); (c) efficacy; (d) safety;
      and (e) overall cost effectiveness. Across all groups, there was a general lack
      of knowledge of NRT effects and its efficacy, with only moderate knowledge of the
      mechanism by which NRT works. Concerns about NRT safety were expressed in all
      groups, with particular apprehension about addictive potential and possible
      interactions with other medications. Among African American smokers in
      particular, there was strong suspicion of pharmaceutical industry and government
      oversight, which coincided with the consensus view that there are too many
      unknowns about NRT. Among Hispanic smokers, there was less suspicion of NRT but a
      strong cultural belief in personal responsibility for smoking cessation. Results
      highlight enduring misperceptions about NRT that likely undermine usage. More
      education about NRT is needed, not only about its efficacy and safety, but also
      with regard to its development and regulation. Health care professionals, many of
      whom are viewed as trustworthy sources of health information, have a particularly
      important role to promote wider use of proven cessation strategies.

PMID- 22364058
TI  - Lessons learned from a black and minority health fair's 15-month follow-up
      counseling.
AB  - BACKGROUND: Little is known about the impact of community health fairs on
      participants' health knowledge, literacy, attitudes, or behaviors. Few health
      fairs have provided followup services for participants. OBJECTIVE: To evaluate
      the short-term (baseline) and long-term (10-month follow-up) health effects of
      exposure to the Indiana Black and Minority Health Fair (BMHF) and to assess the
      impact of personalized 15-month follow-up health counseling sessions for the BMHF
      participants who agreed to the sessions. METHODS: A prospective panel study
      design was utilized with a pre-post test in addition to a cross-sectional survey
      design. RESULTS: Although few behavioral changes were observed between the
      baseline and the precounseling 10-month follow-up, more people perceived
      themselves as overweight (68.1% vs 65.3%, p < .01) and fewer people watched
      TV/videos 4 hours or more on a usual weekday (25.6% vs 47.0%, p <.001) than 10
      months before. After the 15-month follow-up health counseling sessions, the
      intervention group reported substantial and meaningful improvements in self
      reported general health status, health status compared to 6 months earlier,
      percentage of overweight or obese people, choosing leaner meats over those higher
      in fat, snacking while watching TV or videos, and placing a high priority on
      exercise when planning a schedule. CONCLUSIONS: A follow-up component to the
      health fair is not only necessary but also in demand for improving health
      literacy and healthy outcomes for participants. Efforts should be made to
      transform health fair encounters from episodic experiences to long-term
      educational experiences that spur individuals to make the necessary changes to
      enhance their health.

PMID- 22364059
TI  - Significance of plasma C-peptide in obese African American adolescents.
AB  - BACKGROUND: C-peptide blood levels can indicate whether or not a person is
      producing insulin and roughly how much. C-peptide is secreted as a byproduct of
      the biosynthesis of insulin from proinsulin. C-peptide has proposed biological
      activity and a well-established diagnostic value. The significance of C-peptide
      concentration in the plasma and urine in the pediatric population needs further
      delineation. AIM: To determine the significance of plasma C-peptide in obese
      African American adolescents with mild insulin resistance but no evidence of
      diabetes. METHODS: This study included 19 African American adolescents with body
      mass index (BMI) in at least the 85th percentile evaluated with anthropometric
      measurements, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) score,
      and oral glucose tolerance test (OGTT), and 24-hour urine collections. The study
      also included an age-matched control group of 15 healthy African American
      adolescent controls and were not subjected for OGTT. The correlation among BMI,
      fasting plasma C-peptide concentrations, and 24-hour-urine C-peptide
      concentrations was calculated. T Tests were conducted to compare plasma C-peptide
      and 24-hour-urine C-peptide concentrations for the test group and controls.
      RESULTS: Mean HOMA score (3.96 +/- 1.84) signified mild insulin resistance among
      the adolescent test group. The test subjects exhibited adequate glucose tolerance
      (glucose range, 89.4-122.5 mg/dL) during the OGTT. A significant positive
      relationship was observed between BMI and fasting plasma C-peptide concentration
      in the control group (r = 0.537) but not the test group (r = 0.335). An
      insignificant positive relationship was exhibited between BMI and 24-hour-urine C
      peptide concentration in the test group (r = 0.150) and controls (r = 0.254).
      CONCLUSIONS: The positive relationship among BMI, plasma C-peptide, and urine C
      peptide is worth further evaluation in studies conducting multiple rounds of OGTT
      with a larger sample of pediatric subjects. The potential diagnostic value of C
      peptide may facilitate early detection of insulin resistance in the pediatric
      population.

PMID- 22364061
TI  - On the frontline: pediatric obesity in the emergency department.
AB  - Obesity among children is rising at an alarming rate. This study examines
      pediatric emergency department visits for children aged 2 to 17 years to
      determine the prevalence of normal, overweight, and obesity as well as to
      characterize discharge diagnosis and level of service among the different groups.
      The electronic emergency department medical record and billing service data were
      used in the review process. Body mass index (BMI) and percentiles were calculated
      using the Centers for Disease Control formulas with overweight being defined as
      BMI between 85th and 94th sex- and age-specific percentiles and obesity as
      greater than 95th sex- and age-specific percentile. The study was reviewed and
      approved by the institutional review board. Of the 596 patients meeting inclusion
      criteria, there was a predominance of African American and Hispanic patients.
      Approximately 53% (313) of patients were classified as normal weight, while 46%
      (272) of patients were either overweight or obese. The percentages of overweight
      and obesity were similar across racial/ethnic classifications, with a slight
      predominance of obesity among minority groups (30% and 35%, respectively, in
      minority groups vs 28% and 25%, respectively, in nonminority groups). There were
      no statistically significant differences between discharge diagnosis and level of
      service among the different weight categories. Rates of overweight and obesity in
      this predominately minority pediatric population were significantly greater than
      the published national rates. The impact of the epidemic of childhood obesity
      mandates the need for innovative strategies of weight control and reduction.
      Emergency departments routinely treat high-risk pediatric populations and can
      therefore serve as a resource for screening and early referral that has been
      previously untapped in combating childhood obesity.

PMID- 22364060
TI  - Overweight in school-aged children associated with emotional and behavioral
      difficulties: results from a national sample.
AB  - OBJECTIVE: To determine whether there is an association between perceived
      pediatric overweight and emotional/behavioral difficulties among children ages 4
      to 17 years in the United States. DESIGN: A cross-sectional study SETTING:
      Interview of an adult knowledgeable about a child's emotional and physical
      health. All statistical analyses were completed using SPSS 17.0. PARTICIPANTS: A
      total of 7096 noninstitutionalized children aged 4 to 17 years identified in the
      2007 National Health Interview Survey. OUTCOME MEASURES: Included in the 2007
      National Health Interview Survey were 7096 noninstitutionalized children aged 4
      to 17 years. After controlling for age, gender, race, poverty status, education
      of mother, family structure, and health status, this study found that 7.4% of the
      children appeared to be overweight and 5.2% had emotional/behavioral
      difficulties. It also found that caregivers who indicated that their child had a
      problem with being overweight were more likely to report that the child
      experienced emotional/behavioral difficulties compared to caregivers who did not
      report perceived overweight in their child. Characteristics of the children most
      frequently reported to be overweight included Hispanic race, older children (ages
      15-17 years), and those with higher poverty rates and poorer health status.
      CONCLUSION: The continual increase in pediatric overweight and associated
      emotional/behavioral difficulties suggests a need for replicable interventions
      that teach child caregivers to recognize and prevent overweight among vulnerable
      populations.

PMID- 22364062
TI  - Racial and ethnic disparities in physical abuse reporting and child protective
      services interventions in the United States.
AB  - BACKGROUND: Minorities are more prevalent than the general population in the
      child protection system; however, racial/ ethnic disparities in physical abuse
      and child protective services interventions are not understood. METHODS:
      Bivariate and multivariate analyses evaluated racial/ethnic differences in
      reported and substantiated physical abuse, physical abuse deaths, and
      interventions provided in all reported maltreatment from the 2006 National Child
      Abuse and Neglect Data System. RESULTS: In bivariate analyses, African American
      (25%), Asian/ Pacific Islander (21%), and multiracial children (21%) have a
      higher prevalence of substantiated physical abuse than whites (20%). Native
      Americans (0.21%), African Americans (0.15%), Asians/Pacific Islanders (0.12%),
      and Latinos (0.11%) are more likely to die from physical abuse than whites
      (0.09%). African Americans have higher odds than whites of reported (odds ratio
      [OR], 1.13; 95% confidence interval [CI], 1.11-1.14) and substantiated (OR, 1.27;
      95% CI, 1.23-1.31) physical abuse. Latinos have higher odds of reported physical
      abuse (OR, 1.18; 95% CI, 1.16-1.20) and lower odds of substantiated physical
      abuse (OR, 0.93; 95% CI, 0.90-0.96). Native Americans have lower odds (OR, 0.53;
      95% CI, 0.49-0.56) and Asian/Pacific Islanders higher odds (OR, 1.34; 95% CI,
      1.26-1.44) of reported physical abuse vs whites. Latinos have significantly lower
      odds than whites of receiving support services. CONCLUSIONS: Compared with
      whites, African Americans are at increased risk. Latino, Asian/Pacific Islander,
      and multiracial children have greater odds of reports, and Native Americans have
      lower odds of reports for physical abuse. Significant disparities exist in
      interventions provided to minority families. Understanding these disparities has
      the potential to improve reporting, prevention, and interventions.

PMID- 22364063
TI  - A randomized, controlled trial of a school-based intervention to reduce violence
      and substance use in predominantly Latino high school students.
AB  - PURPOSE: Few studies have rigorously evaluated school-based interventions to
      reduce violence and substance use in high school students, especially Latinos.
      This study assessed the effects of a school-based program on reducing violence
      and substance use among primarily Latino high school students. METHODS: Ninth
      grade students at risk for violence and substance use were randomized to
      intervention or control groups. The intervention was based on an existing program
      developed for white and African American youth. Data on smoking, alcohol and drug
      use, fighting, and grades were collected at baseline and 4 and 8 months post
      enrollment. RESULTS: There were 55 students in the control and 53 in the
      intervention group; 74% of controls and 78% of intervention students were Latino.
      There were no significant changes in fighting, smoking, or alcohol or drug use,
      from baseline to 8-month follow-up, between the intervention and control group.
      Pre and post grade point average (GPA) decreased from 2.3 at baseline to 1.8 at
      follow-up (p<.01) in the intervention group, with no significant between-group
      changes in GPA from baseline to follow-up. CONCLUSIONS: This school-based program
      showed no reduction in violence or substance use. The findings suggest that a
      program targeting non-Latino youth may not be optimal for reducing violence and
      substance use in Latinos; greater attention to cultural appropriateness and
      racial/ethnic differences may be needed. There was a decrease in intervention
      group GPA but no significant change compared with controls. Further studies of
      the impact of school-based substance use and violence prevention programs on
      academics, and the effectiveness of afterschool or community-based programs
      compared to school-based programs are needed.

PMID- 22364064
TI  - Low-income children's reported motivators of and barriers to healthy eating
      behaviors: a focus group study.
AB  - BACKGROUND: Despite national attention to the childhood obesity epidemic, there
      are few US-based studies that directly ask children--especially children from low
      income families and from multiple racial/ethnic groups--why they do or do not
      engage in healthy eating behaviors. OBJECTIVE: The purpose of this study was to
      identify motivators of and barriers to healthy eating behaviors, as reported by
      black, Hispanic, and white children from low-income families. METHOD: Six gender-
      and race/ethnicity-concordant focus groups were conducted with 37 children who
      were aged 9 to 12 years and from families with an annual household income of
      $40000 or less. Multiple strategies were used to employ a culturally sensitive
      approach to both data collection and data analysis (eg, a team of culturally
      diverse researchers utilized inductive qualitative analysis to analyze focus
      group transcripts). RESULTS: The motivators of and barriers to healthy eating
      behaviors most commonly reported across the 6 focus groups included social
      influence, taste, issues of availability, weight concerns, and the desire to be
      healthy. A variety of less commonly reported motivators and barriers were also
      discussed. Findings were generally similar across gender and race/ethnicity.
      CONCLUSIONS: Children in this age range can indeed identify a variety of
      motivators and barriers that influence their engagement in healthy eating
      behaviors. Interventions targeting obesity and eating behaviors should include an
      assessment of children's own perceived motivators of and barriers to healthy
      eating.

PMID- 22364065
TI  - Managing chronic kidney disease in type 2 diabetes in family practice.
AB  - Diabetic nephropathy is the leading cause of stage 5 chronic kidney disease (CKD)
      and occurs in 1 in 9 persons with newly diagnosed type 2 diabetes. Screening
      should begin at the time of type 2 diabetes diagnosis to detect the presence of a
      decreased estimated glomerular filtration rate (GFR) and/or an elevated albumin
      excretion rate. The estimated GFR can be used to stage CKD, assess cardiovascular
      risk, and develop treatment strategies. A multifaceted treatment plan delivered
      using a collaborative care approach that fosters person self-management is
      important. Glucose-lowering agents should be selected based on renal function and
      titrated to achieve an A1c less than 7.0%. Lipid-lowering therapy with a statin
      should be utilized to achieve a low-density lipoprotein cholesterol less than 100
      mg/dL, possibly less than 70 mg/dL. An angiotensin-converting enzyme inhibitor,
      angiotensin receptor blocker, or direct renin inhibitor, typically in combination
      with other antihypertensive therapies, is recommended for persons with
      hypertension, microalbuminuria/macroalbuminuria, and type 2 diabetes, as this
      approach has been shown to be renoprotective. Angiotensin-converting inhibitors
      have an additional benefit of improving cardiovascular outcomes in CKD.

PMID- 22364066
TI  - Assessing the readiness of black churches to engage in health disparities
      research.
AB  - We assessed church readiness to engage in health disparities research using a
      newly developed instrument, examined the correlates of readiness, and described
      strategies that churches used to promote health. We pilot tested the instrument
      with churches in a church-academic partnership (n = 12). We determined level of
      readiness to engage in research and assessed correlates of readiness. We also
      conducted interviews with participating pastors to explore strategies they had in
      place to support research engagement. Churches scored fairly high in readiness
      (average of 4.04 out of 5). Churches with a pastor who promoted the importance of
      good nutrition in a sermon or had a budget for health-related activities had
      significantly higher readiness scores than churches without such practices.
      Having a tool to evaluate church readiness to engage in research will inform
      targeted technical assistance and research projects that will strengthen church
      academic partnerships and improve capacity to address health disparities.

PMID- 22364068
TI  - Uninsured African American youths--the need for targeted interventions.

PMID- 22364067
TI  - Clinicians' views of an intervention to reduce racial disparities in diabetes
      outcomes.
AB  - RATIONALE: Interventions that improve clinicians' awareness of racial disparities
      and improve their communication skills are considered promising strategies for
      reducing disparities in health care. We report clinicians' views of an
      intervention involving cultural competency training and race-stratified
      performance reports designed to reduce racial disparities in diabetes outcomes.
      RESEARCH DESIGN AND METHODS: Semistructured interviews were conducted with 12
      physicians and 5 nurse practitioners who recently participated in a randomized
      intervention to reduce racial disparities in diabetes outcomes. Clinicians were
      asked open-ended questions about their attitudes towards the intervention, the
      causes of disparities, and potential solutions to them. RESULTS: Thematic
      analysis of the interviews showed that most clinicians acknowledged the presence
      of racial disparities in diabetes control among their patients. They described a
      complex set of causes, including socioeconomic factors, but perceived only some
      causes to be within their power to change, such as switching patients to less
      expensive generic drugs. The performance reports and training were generally well
      received but some clinicians did not feel empowered to act on the information.
      All clinicians identified additional services that would help them address
      disparities; for example, culturally tailored nutrition advice. Some clinicians
      challenged the premise of the intervention, focusing instead on socioeconomic
      factors as the primary cause of disparities rather than on patients' race.
      CONCLUSIONS: The cultural competency training and performance reports were well
      received by many but not all of the clinicians. Clinicians reported the
      intervention alone had not empowered them to address the complex, root causes of
      racial disparities in diabetes outcomes.

PMID- 22364069
TI  - Fifty years and counting.

PMID- 22364070
TI  - Hospitalization rates differ in African Americans and whites with inflammatory
      bowel disease.

PMID- 22364071
TI  - Response to "Acute agitated delirious state associated with TASER exposure".

PMID- 22364072
TI  - [General internal medicine and general medicine: four years later].

PMID- 22364073
TI  - [Hospital-based internal medicine: year 2011 in chief resident's perspective].
AB  - The year 2011 was full of significant advances in all areas of medicine. Whether
      small or large issues, they all have an impact on daily practice in general
      internal medicine. For example, intravenous administration of diuretics in heart
      failure shows no benefit. But double dose may improve symptoms faster. Direct Xa
      inhibitors are emerging as alternative to anti-vitamin K. beta-blockers reduce
      overall mortality in COPD and do not worsen lung function significantly. Each
      year, the chief residents from the Department of internal medicine at the
      University hospital of Lausanne meet to share their readings. Twelve new
      therapeutic considerations of 2011 are reviewed here.

PMID- 22364074
TI  - [Hospital based internal medicine: a review of 2011].
AB  - Numerous prospective randomised trials recently demonstrated the importance of an
      aggressive approach towards controlling cardiovascular risk factors. New studies
      reinforce the plethora of available data and confirm that interventional
      revascularisation strategies for stable coronary heart disease or cerebral
      vascular disease offer few benefits as compared to medical treatment, and can
      even lead to worse outcomes. This selective review describes some recent studies
      in the areas of cardiovascular disease, pulmonary disease, such as chronic
      obstructive pulmonary disease or screening of lung cancer, and gastroenterology.

PMID- 22364075
TI  - [What was new in ambulatory general internal medicine in 2011?].
AB  - This review of articles published in 2011 covers a large spectrum of topics that
      are of interest for the practice of general internal medicine and of primary
      care. Authors discuss public health issues, such as sleep disorders and their
      relationship with subsequent weight disorders, and the benefits of commercial
      weight reduction programs. Clinical topics, such as the management of victims of
      sexual violence and screening strategies for lung cancer, streptococcal
      pharyngitis, functional bowel disorders and hypertension in ambulatory settings
      are also reviewed. Besides, authors cover therapeutic issues, such as the
      treatment of hand arthritis with chondroitin sulfate and the management of
      plantar warts with salicylic acids and cryotherapy.

PMID- 22364076
TI  - [2011 findings from literature on general internal ambulatory medicine].
AB  - In 2011 several articles seemed significant for the practice of general medicine.
      Diagnosis of hypertension needs several measurements and may need 24-hour
      ambulatory blood pressure monitoring. Glycosylated hemoglobin is a reliable tool
      to diagnose diabetes mellitus. The ABCD2 score with neurological imaging help the
      triage of transient ischemic attacks. Pulmonary embolism can be treated as
      outpatient for low risk patients. Gluten-free diet may be tried in irritable
      bowel syndrome. Nitrofurantoin is a reasonable alternative for simple urinary
      tract infection in women, but antibiotics are not needed after drainage of an
      uncomplicated skin abscess. Subclinical thyroid dysfunction is a risk factor of
      osteoporosis in older men. Sequential use of MMSE and ACE scores is a promising
      approach to assess medical decision-making capacity.

PMID- 22364077
TI  - [Antibiotic prophylaxis in liver cirrhosis].
AB  - Bacterial infections are frequent and severe complications in patients with
      cirrhosis. Spontaneous bacterial peritonitis (SBP) is the most common infection
      in such patients. The risk of recurrence at one year after a first episode of SBP
      is higher than 70% and hospital mortality is estimated between 30-50%. Therefore,
      there is growing interest in antibiotic prophylaxis (ATP) in these patients. Risk
      factors for the occurrence of SBP include low protein level in ascitis, a history
      of previous SBP and an episode of gastrointestinal bleeding. In all three
      situations, the indication of ATP, reviewed in this paper, is recognized and
      improves survival.

PMID- 22364078
TI  - [Urban health: the irremediable urbanization of life and medicine].
AB  - Since 2007, the number of people living in cities exceeds that of rural areas.
      Thus, cities and their organizations have a major influence on all spheres of
      human life, especially health. This influence may generate inequality, suffering
      and disease, but also represent an opportunity for health and well-being. This
      paper introduces the concept of urban health, particularly in terms of primary
      care medicine and presents solutions that encompass a wide field (politics, urban
      planning, social inequality, education). Improving urban health requires
      collaboration of medical with non-medical actors, in order to become of
      development (re-) urban structure and promotes the health of all.

PMID- 22364079
TI  - [Do not say more Botox!].

PMID- 22364080
TI  - [To implant two or three embryos? That is no longer the question].

PMID- 22364081
TI  - [Eels, carp, bream and other pyralenes ].

PMID- 22364083
TI  - [An interhemispheric conflict].

PMID- 22364084
TI  - Salmonella enterica serovar Paratyphi A: an emerging cause of febrile illness in
      Nepal.
AB  - With an aim to evaluate the isolation rate and antibiotic susceptibility pattern
      in Salmonella enterica serovar Typhi and S. Paratyphi A, 656 blood samples
      collected from clinically diagnosed enteric fever patients at National Public
      Health Laboratory, Nepal during January through December 2008 were processed.
      Isolates were identified by standard microbiological procedures including
      serotyping. Antibiotic susceptibility testing was performed by disc diffusion
      method and minimum inhibitory concentration (MIC) to ciprofloxacin, ofloxacin and
      nalidixic acid was determined by agar dilution method following CLSI guidelines.
      Altogether 59 isolates of S. Typhi (49.15%) and S. Paratyphi A (50.85%) were
      recovered. A total of 80% isolates were resistant to nalidixic acid with S.
      Paratyphi A (93%) showing significantly higher resistance (P < 0.05) compared to
      S. Typhi (66%). The nalidixic acid resistant S. Paratyphi A strains required
      significantly higher MICs (P < 0.001) to quinolone (MIC expressed as mean +/- SD
      for nalidixic acid 477.87 +/- 87.02 microg/mL, ofloxacin 1.8 +/- 0.63 microg/mL,
      ciprofloxacin 0.62 +/- 0.3 microg/mL) compared with that of S. Typhi (nalidixic
      acid 173.18 +/- 72.03 microg/mL, ofloxacin 0.43 +/- 0.11 microg/mL, ciprofloxacin
      0.25 microg/mL). Increased MIC of fluoroquinolone (FQ) is of particular concern
      in emerging strains of S. Paratyphi A as exposure to these drugs fuels up further
      development of full FQ resistant populations. Use of FQs as the first-line drugs
      for empirical therapy and management of enteric fever in areas where these
      strains are prevalent is questionable and requires an urgent review.

PMID- 22364085
TI  - Rheumatoid arthritis: a review and dental care considerations.
AB  - Rheumatoid arthritis (RA), is a chronic multisystem disease of presumed
      autoimmune etiology. Medical complications due to RA and its treatment may affect
      the provision of oral health care. Associated syndromes may contribute to a
      patient's susceptibility to infections and impaired hemostasis. Therefore oral
      health care providers need to recognize and identify modificationsof dental care
      based on the medical status of patients with RA. As with many other chronic
      conditions, early intervention can reduce the severity of the disease.
      Furthermore, oral health care providers play an important role in the overall
      care of these patients as it relates to early recognition, as well as control of
      the disease.

PMID- 22364086
TI  - Long-term effects in ovaries of the adult mice following exposure to monosodium
      glutamate during neonatal life--a histological study.
AB  - Monosodium Glutamate (MSG) has been in use since long as a flavour enhancing
      substance. Its widespread use has also earned it a bad name to be harmful for
      human health. It had been incriminated in wide range of effects comprising
      retinal degeneration, metabolic disorders, endocrinal disorders including reduced
      fertility rate in both in both sexes in mice. However there were many
      contradicting views too, which have prompted us to undertake the present study.
      For our study eight female newborns of Swiss Albino mice were injected
      subcutaneously with MSG (2mg / gm of body wt. in a dilution 40 mg of per ml. of
      distilled water) on completion of 2nd, 4th, 6th, 8th and 10th day of life.
      Another five mice pups were injected with same volume of distilled water and
      taken as control. On completion of 75 days the mice were sacrificed of, ovaries
      were collected through dissection, 5 micron thick sections were cut and stained
      by H and E and PAS stain and studied under light microscope. It was observed from
      the quantitative analysis of the ovarian tissue that there was increase in the
      number of the primary follicle without increase in number of Graffian follicle in
      the experimental group.

PMID- 22364087
TI  - Resistotypes of Vibrio cholerae 01 Ogawa Biotype El Tor in Kathmandu, Nepal.
AB  - Cholera continued to be a major diarrheal illness in Nepal and antibiotic
      resistance has appeared as a serious problem in cholera management. The study
      aimed at analyzing the distribution pattern of the resistotypes (R-types) of
      Vibrio cholerae in the Kathmandu valley, Nepal. During June 2008 to January 2009,
      210 diarrheal specimens received at National Public Health Laboratory from
      suspected cholera patients were subjected to standard bacteriological
      investigation including biotyping and serotyping. Antimicrobial susceptibility
      pattern of V. cholerae isolates was determined by Kirby Bauer disc diffusion
      method following CLSI guidelines. A total of 57 (27%) V. cholerae isolated were
      recovered, all of which belonged to 01 Ogawa Biotype EL Tor. Based on
      antibiogram, V. cholerae isolates in our study revealed three distinct R-types: R
      type I, R-type II and R-type III. All three R types showed resistance to
      furazolidone, nalidixic acid and cotrimoxazole while sensitive to ciprofloxacin
      and tetracycline. Additional resistance to ampicillin and erythromycin was
      observed respectively in R-type II and III. Different R-types showed unique month
      wise variations (P < 0.05). Differentiation of V. cholerae strains into R-types
      is an important tool. In addition to direct patient management, it may have
      implication in identifying the source and spread of infection, and understanding
      the distribution pattern in a particular geographical region.

PMID- 22364088
TI  - A morphometric study of human pancreas in Nepalese people.
AB  - Considering the seriousness of pancreatic diseases and the utmost importance of
      its correct diagnosis and treatment, a morphometric study of pancreas among
      Nepalese population has emerged as a demand of present time. This study was
      carried out to establish a normal dimension of pancreas which could be a
      guideline for the correct diagnosis, treatment and research on various diseases
      related to it. Thus, a descriptive type of study was done within a period of
      eight years of time (2004-2011) on 40 pancreases of both sexes and different age
      groups, collected from embalmed cadavers from four medical colleges of Kathmandu,
      Nepal. The obtained specimens of pancreas were classified according to the age
      and sex. Simultaneously, the weight and length were measured. The data was
      statistically analyzed and compared, which revealed that the mean size of
      pancreas was significantly larger in below forty years of age group. Although,
      there was no significant difference in the size of pancreas between male and
      female, the pancreas of male subjects was found larger. Thus, the result of the
      present study not only provides standard dimension of pancreas in Nepalese
      peoples but also reveals that it is larger in younger people and males.

PMID- 22364089
TI  - Profile of vernal keratoconjunctivitis in Nepal: a hospital based study.
AB  - Vernal keratoconjunctivitis (VKC) or Spring Catarrh is recurrent, chronic,
      allergic conjunctivitis occurring in prepubertal age-group during spring and
      summer season. Though this is a self-limiting disorder, it often leads to visual
      impairment due to secondary corneal complications if not treated during active
      stage of the illness. Apart from this, the illness is known to affect the
      productivity and quality of life in school going children due to absenteeism and
      limitations to outdoor activities. Knowing the clinical profile of disease would
      provide the evidence for developing, treatment protocol in coming years.
      Therefore a hospital based study was designed to see the profile of VKC. Total of
      220 patients were enrolled in this study. Male to female ratio with VKC was found
      to be 4:1. Clinical presentation showed seasonal variation; 78.2% during the
      spring and summer season. Bilateral involvement was seen in 100% cases, out of
      which 44.5% were limbal type. The best spectacle corrected visual status of
      better than 6/9 was in 96.4%, while 2.3% had vision less than 6/12. In 9.5%
      corneal involvement was seen as superficial keratopathy, while others, such as
      Shield ulcer, pannus, corneal scar, and keratoconus consisted of 8.3%. The
      disease is predominantly seen in male child with seasonal variation. Visual
      impairment is mainly due to involvement of cornea.

PMID- 22364090
TI  - A study of sexual dimorphism in permanent mandibular canines and its implications
      in forensic investigations.
AB  - Teeth are well preserved after death and they exhibit remarkable sexual
      dimorphism. Hence, they provide excellent materials for forensic investigations
      intended for identification of sex. Present study was undertaken on permanent
      mandibular canines of 90 male and 90 female subjects of age group 17-23 years.
      The mesiodistal width for right and left mandibular canines and intercanine
      distance were measured. Subsequently, canine index was calculated for both sides.
      Significant sexual dimorphism was found in all parameters except intercanine
      distance. All the results were compared with previous studies and discussed in
      the light of genetic, evolutionary and metabolic reasons for sexual dimporhism.

PMID- 22364091
TI  - Status of intestinal parasitosis among hospital visiting patients in Deukhury
      Valley, Dang, Nepal.
AB  - Intestinal parasitosis is highly prevalent among the general population in Nepal.
      This study aimed to assess the status of intestinal parasitosis among patients
      attending Deukhury Community Hospital, Lamahi, Dang, situated in the mid western
      region of Nepal. A total of 210 stool samples examined by direct smear technique
      were reported. The overall prevalence of intestinal parasitic infection was found
      to be 21.4% (M = 23.5% vs F = 19.3%). Children < 15 yrs age were infected more
      often as compared to > 60 yrs and 15-60 yrs aged people. Among adults, Entamoeba
      histolytica infection was found to be very high compared to high helminthic
      infection found among children. Finding showed that, the prevalence was
      significantly high (68.8%) among people having low socio-economic status compared
      to others (31.1%) (p < 0.05). Among various parasites detected, E. histolytica
      was the most common parasite (48.8%) followed by helminths, mainly Ascaris
      lumbricoides (31.1%), hookworm (13.3%), Trichuris trichiura (4.4%) and Taenia
      species (2.2%) respectively in the locality.

PMID- 22364092
TI  - Tweeds analysis of Nepalese people.
AB  - The aim of the present study was to establish the Tweed's norms for Nepalese
      people, compare the values between the Nepalese male and female samples as well
      as to compare with the Caucasians. One hundred lateral cephalogram was taken by
      the same x- ray technician and later traced by manually and all three angular
      parameters Frankfort Mandibular plane Angle (FMA), Frankfort Mandibular Incisal
      Angle (FMIA), Inciso Mandibular Plane Angle (IMPA) were measured and found to be
      28 degrees, 56 degrees and 96 degrees respectively. There was no clinical
      significant different between Nepalese male and female but there is highly
      significant among Nepalese and Caucasian.

PMID- 22364093
TI  - Asymptomatic bacteriurea among pregnant women visiting Nepal Medical College
      Teaching Hospital, Kathmandu, Nepal.
AB  - Urinary tract infection is the commonest bacterial infection in pregnancy. The
      overall incidence is 5.0-10.0% of all pregnancy. During pregnancy bacterial
      growth is favoured by increased urinary content of glucose, aminoacids and other
      nutrients. Other factors responsible for infection are basically related to
      hormonal effect and mechanical factors. Prolonged stasis of urine in urinary
      bladder favours growth of micro organism, relaxation of vesico-ureteric junction
      leads to reflux of urine from bladder to ureter and later up to renal pelvis and
      later can affect the renal parenchyma affecting the function of kidneys. In
      addition, some maternal defense mechanism are less effective during pregnancy.
      Bacteriuria either asymptomatic (5.0%) or symptomatic is common in pregnancy, if
      left untreated, asymptomatic bacteriuria will lead to acute pyelonephritis in
      20.0-30.0%. This may result in abortion, premature delivery, low birth baby and
      even still birth. About 12.0% of antenatal admission are sepsis due to
      pyelonephritis. Keeping in mind that UTI in pregnancy leads to increase in
      maternal morbidity as well as neonatal morbidity and mortality. In this
      prospective study all asymptomatic consecutive antenatal women were included 200
      from each trimester with total of 600 in number to see the incidence in different
      trimester, most prevalent organisms and it's sensitivity. They were followed up
      till delivery to see the incidence of asymptomatic bacteriurea in different
      trimester and its outcome in terms of type of delivery, baby weight, apgar score
      given at the time of birth and hospital admission for morbidity.

PMID- 22364095
TI  - Clinical profile of patients with cirrhosis of liver in a tertiary care hospital,
      Dharan, Nepal.
AB  - One hundred and five (72 males; 33 females) consecutive patients who met the
      inclusion criteria were studied. The mean age of the patients was 49.06 +/- 11.27
      years (range 23-73 years). Ninety patients were adult cirrhotics (age > or = 35
      yrs) and the remaining 15 patients were young (age < or = 35 yrs). Ninety out of
      105 patients were having alcohol related cirrhosis. The commonest presenting
      symptoms were abdomen distension (100% in young cirrhotics vs. 84.4% in adult
      cirrhotics) and jaundice (93.3% in young cirrhotics vs. 84.4% in adult
      cirrhotics). The most common presenting signs were ascites (100% in young
      cirrhotics vs. 84.4% in adult cirrhotics) and icterus (93.3% in young cirrhotics
      vs. 84.4% in adult cirrhotics), followed by loss of body hair (73.3% vs. 71.1% in
      young and adult cirrhotics respectively) and spider naevi (46.7% vs. 61.1% in
      young and adult cirrhotics respectively). Sixty percent of young cirrhotics and
      52% of adult cirrhotics were in Child's grade C at the time of presentation. Most
      of the deaths were seen in Child's grade C of liver disease. Alcoholic cirrhosis
      is common in the eastern part of Nepal. Cirrhosis is not uncommon in younger age
      group. Abdomen distension and jaundice were most common clinical presentations.
      Most patients were in Child's grade C and most deaths were due to hepatic
      failure.

PMID- 22364094
TI  - Different pharmacological solutions in intracanal irrigation.
AB  - Irrigation of root canals during endodontic therapy is an important step. Sodium
      hypochlorite (NaOCl), hydrogen peroxide (H2O2), chlorhexidine (CHX) and normal
      saline are commonly used intracanal irrigants to disinfect and clean the root
      canals. This prospective study was set to observe the efficacy of normal saline
      (0.9% NaCl) irrigation with sequential irrigation of 3% H2O2, 5.2% NaOCl and 0.9%
      NaCl. A total number of 228 dental patients were screened and 104 patients
      fulfilling the inclusion criteria were enrolled for the endodontic therapy of
      mature permanent teeth for the period of one year. Two treatment groups were
      constituted in which patients were randomly allocated equally in each treatment
      group. Post-obturation pain, swelling, analgesic use and eight weeks post
      obturation radiological evaluation of the patients were carried out as the
      measurement of clinical and radiological success of the endodontic treatment. No
      statistically significant differences were observed in the measured treatment
      outcomes between two groups. However, studies involving larger sample size and
      longer post-obturation follow up are recommended for the further either
      confirmation or rejection of present findings.

PMID- 22364096
TI  - Clinical profile of tuberculosis in children.
AB  - Childhood tuberculosis is common in our community. The diagnosis in most cases is
      still based on clinical evidence alone. The present study was designed to study
      clinical profile, laboratory investigations and outcome of pediatric
      tuberculosis. A prospective study was conducted among the children admitted in
      Nepal Medical College from April 2007 to March 2011. The prevalence of
      tuberculosis was 1.5%. Pulmonary tuberculosis was common (53.7%) than extra
      pulmonary (46.3%) tuberculosis. BCG scar was present in 48.8%. History of
      tuberculosis contact was present in 36.6% and Mantoux test was positive in 39.0%.
      The most common symptoms were fever (75.6%), cough (63.4%) and weight loss
      (41.5%). Confirmed diagnosis was made (bacteriological or histological) only in
      14.6%. This study supports the use of history and clinical features to diagnose
      childhood tuberculosis.

PMID- 22364097
TI  - Malarial nephropathy in a tertiary care setup--an observational study.
AB  - Malaria is endemic in Nepal. Its poor outcome is associated with acute renal
      failure (ARF), hepatopathy and cerebral malaria. The clinical profiles,
      biochemical parameters and outcome of 25 patients of falciparum malaria diagnosed
      either by optimal test, peripheral blood smear (PBS) or Quantitative buffy coat
      (QBC) admitted in BP Koirala Institute of Health Sciences were studied. Majority
      of patients (84%) was from the age group 15-45 years. Mean age was 33 +/- 16
      years. There were 16 males and 9 females. All had history of fever. Twenty
      patients were optimal positive, 9 positive in PBS and 12 were QBC positive for
      Plasmodium falciparum. Mean duration of fever was 13 +/- 9 days. Patients with
      renal or hepatic involvement presented earlier. Renal dysfunction (S. creatinine
      > 1.5 mg/dl) was present in 60%. Ten patients had ARF (S. creatinine > 3 mg/dl);
      five out of them were oliguric/anuric. S. creatinine in patients without renal
      dysfunction, with renal dysfunction but without renal replacement therapy (RRT)
      and who underwent RRT were 1.1 +/- 0.24, 3.98 +/- 1.9 and 4.53 +/- 1.72 mg/dL
      respectively. Serum creatinine of patients with and without hepatic dysfunction
      respectively were 3.26 +/- 1.98 and 1.26 +/- 0.48 mg/dL (p = 0.001 (CI 0.9
      3.10)). Total bilirubin of > 2.5 mg/dl was present in 77%. Total bilirubin of
      patients with renal dysfunction who underwent and who did not undergo RRT were
      10.3 vs. 3.76 mg/dL (p = 0.024 (CI 1.07-12.0)). Fourteen patients had cerebral
      malaria. Eight patients underwent RRT (hemodialysis or peritoneal dialysis). Six
      patients died. Five died within 48 hrs of presentation. Patients who had renal
      and/or hepatic dysfunction had increased morbidity and mortality.

PMID- 22364098
TI  - Iodine supplementation in pregnancy and its effects on perinatal outcome.
AB  - Iodine is an important micronutrient for mental growth and development. Limited
      information is available on the role of iodine supplementation in pregnancy and
      its effect on perinatal outcome. We designed intervention study to assess the
      effect of iodine supplementation during second half pregnancy and its effect on
      perinatal outcomes (maternal and neonatal health). Among 60 intervened with oral
      iodine tablet in pregnancy and 60 control pregnant women in Sindhupalchowk
      District Hospital Chautara, we assessed maternal and neonatal health after the
      delivery. The significant differences were found among duration of pregnancy,
      weight of pregnant mother before and after intervention of at least three months
      duration (56.1 kg vs. 59.6 kg, p < 0.001), weight of neonate (3.3 kg in
      intervention vs. 3.0 kg in control, p < 0.001), and thyroxin hormone (1.1 ng in
      intervention vs. 1.2 ng in control, p < 0.001) of women between intervened and
      control subjects. Therefore, regular supplementation of iodine in oral form for
      more than three months during pregnancy preferably during early stage will bring
      significant positive changes in perinatal outcomes.

PMID- 22364099
TI  - In health--vital capacity is maximum in supine position.
AB  - Vital capacity, frequently measured clinically as an index of pulmonary function,
      gives useful information about the strength of respiratory muscles and other
      aspects of lung functions. It is generally noted in sitting position. As in the
      supine position, respiratory excursions of diaphragm is highest in normal
      breathing, this study was planned to note whether there occurred any alteration
      in vital capacity in supine position in comparison to that noted in sitting
      position. Young sedentary non smoker healthy medial students (n = 100, age 19-22
      years) of Nepal Medical College participated as volunteers in this study. Body
      mass index (BMI) of each of them was calculated. Vital capacity was noted in
      sitting position and in supine position with the help of a spirometer, following
      the standard procedure. Result exhibited greater vital capacity in supine posture
      than in sitting position in the same individual. Diaphragm is the major muscle of
      inspiration, responsible for some two-thirds of the vital capacity. Naturally, in
      supine posture the scope of diaphragmatic movements increased and as a result,
      vital capacity exhibited greater value in comparison to that recorded in sitting
      posture.

PMID- 22364100
TI  - Monthly pattern of psychiatric morbidity and duration of stay among the patients
      admitted in Mental Hospital, a central level tertiary care hospital.
AB  - Psychiatric morbidity is a major public health problem in the world across
      developed and developing countries. There is a paucity of Nepalese studies on
      psychiatric morbidity. All the patients who were admitted in mental hospital,
      Lagankhel from 17th July 2009 to 16th July 2010 were included in this study.
      Information on their Socio-demographic profiles and hospital diagnosis was
      extracted from their clinical notes. Eight hundred and fifty two patients were
      included in this study. Fifty eight percent were males. More than sixty percent
      of the patients were aged between 21 and 40 years. Sixty patients were married.
      In terms of ICD 10 diagnosis, the most common diagnoses were Schizophrenia in 427
      (50.1%), mood disorders in 286 (33.5%) and substance use disorder in 80 (9.3%).
      In terms of length of stay, majority of them (56.4%) had stayed for 0-14 days.
      Thus, there is a need to increase the awareness in the general public regarding
      the impact of mental illness and the need for timely treatment.

PMID- 22364101
TI  - Nepal health sector decentralization in limbo: what are the bottlenecks?
AB  - Nepal's efforts to decentralize its governance date back to over half a century.
      These efforts remained incomplete due to different reasons including
      administrative responses and political development affecting its implementation.
      The Local Self Governance Act (LSGA), 1999 envisaged, for the first time, to
      decentralize governance in the health sector through devolution of
      responsibilities, authority and resources to the local bodies. However, the pace
      of health sector decentralization in Nepal even after the LSGA was enacted has
      not progressed satisfactorily due to different reasons. The purpose of this paper
      is to discuss why health sector decentralization in Nepal has not advanced as
      expected. This paper identifies many issues--policy related, political,
      functional, and institutional--as stumbling blocks for health sector
      decentralization of Nepal. More specifically, the major bottlenecks for progress
      are lack of a clear cut policy, poor coordination among different sectors,
      improper handover process, lack of elected bodies, poor selection process of
      management committees, lack of coherence in the capacity building process of
      local bodies, ongoing debate about state restructuring including federalism and
      different political ideologies on decentralization.

PMID- 22364102
TI  - Surgical site fire: a case of evil spirit or lapsed communication?
AB  - Electrocautery has become an indispensable tool in the operating room mainly to
      achieve bloodless surgical field. However, it does carry several risks including
      fire burn. Abundant fuels and oxidizer in operation theatre in the presence of
      electrocautery can easily get ignited, imposing serious risk to the patient and
      health professionals. This report of a case of surgical site burn injury due to
      unintentional reuse of a spirit soaked gauze piece intends to create awareness
      among health professionals and staff regarding such serious complication.

PMID- 22364103
TI  - Pulmonary cryptococcosis and tuberculoma mimicking primary and metastatic lung
      cancer in 18F-FDG PET/CT.
AB  - 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely
      incorporated in cancer management. Although, it has increased sensitivity, 18F
      FDG is not tissue specific thus posing diagnostic dilemma in certain situations.
      False positivity in pulmonary nodules have been seen in various inflammatory,
      infective as well as post operative conditions while false negativity is common
      with adenomas, low grade lymphomas, bronchoalveolar carcinomas and carcinoid
      tumors. We present two cases of granulomatous diseases as pulmonary
      cryptococcosis and tuberculosis showing false positivity in a resected colorectal
      cancer patient and highlight the importance of recognition of this entity in an
      endemic region for granulomatous infections.

PMID- 22364104
TI  - Neuroleptic malignant syndrome: case report.
AB  - Neuroleptic Malignant Syndrome (NMS), a potentially fatal complication of
      neuroleptic therapy is described. It is found to be associated with a variety of
      medical and psychiatric conditions. Various risk factors and non specific
      investigations pathognomic to various medical conditions has been proposed. The
      mortality and morbidity associated with NMS can be decreased with early
      recognition, early discontinuation of the neuroleptics and aggressive treatment.

PMID- 22364105
TI  - Synthesis of uranium(VI) terminal oxo complexes: molecular geometry driven by the
      inverse trans-influence.
AB  - Oxidation of our previously reported uranium(V) oxo complexes, supported by the
      chelating ((R)ArO)(3)tacn(3-) ligand system (R = tert-butyl (t-Bu), 1-t-Bu; R = 1
      adamantyl (Ad), 1-Ad), yields terminal uranium(VI) oxo complexes
      [(((R)ArO)(3)tacn)U(VI)(O)]SbF(6) (R = t-Bu, 2-t-Bu; R = Ad, 2-Ad). These
      complexes differ in their molecular geometry in that 2-t-Bu possesses pseudo-C(s)
      symmetry in solution and solid state as the terminal oxo ligand lies in the
      equatorial plane (as defined by the three aryloxide arms of the ligand) in order
      to accommodate the thermodynamic preference of high-valent uranium oxo complexes
      to have a sigma- and pi-donating ligand trans to the oxo (vis-a-vis the ubiquity
      of the linear UO(2)(2+) moiety). The distortion of the ligand--which stands in
      contrast to all other complexes of uranium supported by the ((R)ArO)(3)tacn(3-)
      ligand, including 2-Ad--is most clearly seen in the structures of 2-t-Bu, [(((t
      Bu)ArO)(3)tacn)U(VI)(O)(eq)]SbF(6), and 3-t-Bu, [(((t
      Bu)ArO)(3)tacn)U(VI)(O)(eq)(OC(O)CF(3))(ax)]. The solid-state structure of 3-t-Bu
      reveals that the trans U-O(ArO) bond length is shortened by 0.1 A in comparison
      to the cis U-O(ArO) bonds and the trans U-O-C(ipso) angle is linearized (157.67
      degrees  versus 147.85 degrees  and 130.03 degrees ). Remarkably, the minor
      modification of the ligand to have Ad groups at the ortho positions of the
      aryloxide arms is sufficient to stabilize a C(3v)-symmetric terminal uranium(VI)
      oxo complex (2-Ad) without a ligand trans to the oxo. These experimental results
      were reproduced in DFT calculations and allow the qualitative bracketing of the
      relative thermodynamic stabilization afforded by the inverse trans-influence as
      ~6 kcal mol(-1).

PMID- 22364106
TI  - The successes and limitations of preclinical studies in predicting the
      pharmacodynamics and safety of cell-surface-targeted biological agents in
      patients.
AB  - To improve drug development outcomes, it is important to review when preclinical
      pharmacodynamic and safety models have successfully predicted human responses and
      when they have not. In a recent issue of the BJP, Bugelski and Martin examined
      the concordance between preclinical and human data for biopharmaceuticals
      targeted to cell-surface proteins. The cases are interesting and several trends
      emerge. The pharmacodynamics of biopharmaceuticals in non-human primates is
      largely predictive; the use of surrogates in rodents may be similarly predictive,
      allowing for more conservative use of non-human primates. While overall
      concordance of preclinical toxicology data and clinical safety was poor, this is
      largely a reflection of the immunomodulatory biology of the majority of the
      biopharmaceuticals evaluated. The examples show that adverse effects in animals
      that were the result of direct and/or exaggerated pharmacology were modelled
      well, but that specific infections or other indirect outcomes of
      immunomodulation, along with cytokine-related events, were not modelled well in
      preclinical studies.

PMID- 22364108
TI  - Dexamethasone has variable effects on mesenchymal stromal cells.
AB  - BACKGROUND AIMS: Dexamethasone (Dex) is a potent synthetic member of the
      glucocorticoid class of steroid drugs. Frequently, Dex has been used to enhance
      osteogenic, chondrogenic and adipogenic differentiation of mesenchymal stromal
      cells (MSC). Recently, Dex was applied to promote MSC proliferation, because of
      the rare frequency of MSC in bone marrow, and could protect the cells from
      apoptosis. The effects of Dex on MSC cytobiology behavior needs to be
      investigated. METHODS: MSC were obtained from human umbilical cord. The surface
      phenotype and functional characterization of MSC cultured with different
      concentrations of Dex were investigated, in comparison with a control group,
      including MSC proliferation, apoptosis, cytokine expression and
      immunosuppression. RESULTS: Different concentrations of Dex exerted diverse
      effects on MSC proliferation and apoptosis. Dex was also able to affect the
      pattern of cytokine expression of MSC. Furthermore, Dex impaired
      immunosuppression of MSC on peripheral blood mononuclear cells. CONCLUSIONS: A
      low dose of Dex favors MSC expansion in vitro, and protects against apoptosis. It
      is not suitable for MSC to be pre-treated with Dex when they are to be used to
      treat immunologic disease. However, when MSC are applied to promote angiogenesis,
      it is beneficial for them to be pre-treated with 10(-9) mol/L Dex.

PMID- 22364109
TI  - Improving diabetes self-management by mental contrasting.
AB  - Diabetes patients often fail to adhere to self-management activities, such as
      losing weight by exercising and dieting. The present study tested the efficacy of
      a minimalist intervention consisting of only the self-regulation strategy 'mental
      contrasting' (Oettingen, G. (2000). Expectancy effects on behavior depend on self
      regulatory thought. Social Cognition, 18, 101-129) in promoting these self
      management activities among a clinical sample of type 2 diabetes patients (N =
      64). Half of the participants were assigned to a positive indulging condition
      (fantasising about positive outcomes of losing weight) and the other half of the
      participants were assigned to a mental contrasting condition (fantasising about
      positive outcomes of losing weight and then contrasting these fantasies with
      obstacles in the present reality). Results showed that, one month later,
      participants in the mental contrasting condition had improved their diabetes self
      management, and in particular their dieting behaviour, by a larger extent than
      participants who merely indulged in the positive future. It was concluded that
      although more elaborate interventions may yield stronger results, adding a mental
      contrasting exercise to their usual care may be a highly feasible, low-cost
      alternative to promote diabetes self-management.

PMID- 22364111
TI  - Comparison of inhaled corticosteroids and leukotriene receptor antagonists in
      adolescents and adults with mild to moderate asthma: a meta-analysis.
AB  - INTRODUCTION: Inhaled corticosteroids (ICS) and oral leukotriene receptor
      antagonists (LTRA) are effective drugs used in the management of asthma as
      controller monotherapy in adolescents and adults, although there are debates as
      to which one is better. OBJECTIVES: To thoroughly compare the efficacy and
      tolerability of ICS vs LTRA in adolescents and adults with mild to moderate
      asthma. METHODS: Relative database were searched for the review. Randomized
      controlled trials of more than or equal to 4 weeks' treatment duration comparing
      ICS with LTRA were reviewed. RESULTS AND CONCLUSION: Twenty-four trials with 6197
      randomized adolescents and adults with mild to moderate asthma met the inclusion
      criteria with a minimum duration of 4 weeks' treatment. Significant differences
      favouring ICS were found in all indices of pulmonary function. Other significant
      benefits of ICS were shown in symptoms, nocturnal awakenings, rescue-medication
      use, symptom-free days and quality of life. As to each special symptom of adverse
      effects, ICS was similar to LTRA in the incidence of headache, nausea and throat
      discomfort, but significantly higher in the incidence of hoarseness and oral
      pharyngeal candidiasis. Concerning withdrawal because of adverse events
      potentially related to treatment, ICS was similar to LTRA but significantly
      superior to LTRA in decreasing the asthma exacerbations or attacks during the
      treatment period. These results show that ICS may be the better drug in terms of
      efficacy and tolerability, except hoarseness and oral pharyngeal candidiasis, and
      should thus have priority over LTRA in asthma monotherapy in adolescents and
      adults.

PMID- 22364110
TI  - Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer
      receiving haemodialysis: a retrospective Italian survey.
AB  - What's known on the subject? and What does the study add? Sunitinib and sorafenib
      are orally administered multikinase inhibitors approved for the treatment of
      advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib
      suggest that haemodialysis does not significantly alter plasma concentrations. In
      this retrospective study we define the safety and efficacy of tyrosine kinase
      inhibitors in patients with metastatic RCC (mRCC) and end-stage renal disease
      requiring haemodialysis. Even though the retrospective nature of this survey and
      the relatively small sample size represent major limitations, these data indicate
      that treatment with sunitinib and sorafenib in this cohort of patients is
      feasible with no unexpected toxicity and good efficacy, results similar to those
      in the general population of patients with mRCC. OBJECTIVE: To investigate the
      safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with
      metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring
      haemodialysis (HD). PATIENTS AND METHODS: Between July 2006 and December 2010, 24
      patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in
      14 Italian institutions. We retrospectively reviewed the medical records of these
      patients to evaluate the administered doses of TKIs, treatment-related toxicities
      and the clinical response to therapy. RESULTS: Sunitinib was administered at 50
      mg daily for 4-6 weeks in six patients, 37.5 mg daily for 4-6 weeks in seven
      patients (one patient subsequently increased the dose to 50 mg daily), 25 mg
      daily for 4-6 weeks in two patients and 12.5 mg daily for 4-6 weeks in one
      patient. Among the eight patients treated with sorafenib, four patients received
      800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200
      mg daily with a continuous schedule. The estimated median progression-free and
      overall survival periods of this cohort of patients were 10.3 months and 22.6
      months, respectively. With regard to tolerability and safety, no unexpected
      adverse events were registered and no grade 4 haematological or non
      haematological toxicities were reported. CONCLUSIONS: Sunitinib and sorafenib
      treatment is not contraindicated in patients with mRCC undergoing HD. The outcome
      of this patient population is similar to that observed in patients with normal
      renal function treated with TKIs. These results merit further confirmation by a
      larger prospective trial.

PMID- 22364112
TI  - A case of the flu.

PMID- 22364113
TI  - Assessing the representativeness of Canadian Hospitals Injury Reporting and
      Prevention Programme (CHIRPP) sport and recreational injury data in Calgary,
      Canada.
AB  - The objective of this study was to assess the representativeness of sport and
      recreational injury data from Canadian Hospital Injury Reporting and Prevention
      Programme (CHIRPP) in Calgary. Internal representativeness was assessed by
      comparing CHIRPP and regional health administrative data (ambulatory care
      classification system-ACCS) at Alberta Children's Hospital (ACH). External
      representativeness was assessed by comparing CHIRPP with ACCS at all hospitals.
      Comparisons were performed using descriptive statistics for top injury-producing
      sports and sports that produced severe injuries. Stratified distributions of
      injury-producing sports by gender, age group and severity of injury in CHIRPP and
      ACCS were compared. The proportion of all injuries in Calgary captured by CHIRPP
      was 64.8% (99%CI: 64.02-65.54%) (16,977/26,206). CHIRPP captured more cases of
      top injury-producing sports than ACCS at ACH. Rankings of top injury-producing
      sports in CHIRPP and ACCS at ACH were remarkably consistent (rho  = 0.92, p <
      0.0001). Rankings of top injury-producing sports in CHIRPP and ACCS at all
      hospitals were almost identical (rho  = 0.98, p < 0.0001). Stratified
      distributions of top injury-producing sports by gender, age group and the
      severity of injury showed strong consistency between CHIRPP and ACCS. It is
      concluded that CHIRPP in Calgary provides a representative profile of injuries
      compared to regional health administrative data. This project supports the use of
      CHIRPP for establishing injury prevention priorities.

PMID- 22364114
TI  - Pedometer-determined physical activity is linked to low systemic inflammation and
      low arterial stiffness in Type 2 diabetes.
AB  - AIMS: The aim of this study was to explore the association between pedometer
      determined physical activity versus measures of obesity, inflammatory markers and
      arterial stiffness in people with Type 2 diabetes. METHODS: We analysed data from
      224 men and 103 women with Type 2 diabetes, aged 54-66 years. Physical activity
      was measured with waist-mounted pedometers during three consecutive days and the
      number of steps/day were calculated and classified in four groups: < 5000
      steps/day, 5000-7499 steps/day, 7500-9999 steps/day and >= 10000 steps/day. Blood
      samples were analysed for lipids, HbA(1c), inflammatory markers including C
      reactive protein and interleukin-6. Nurses measured blood pressure and
      anthropometrics. Aortic pulse wave velocity was measured with applanation
      tonometry over the carotid and femoral arteries. RESULTS: Mean steps/day was 7683
      +/- 3883 (median 7222, interquartile range 4869-10,343). There were no
      differences in age, diabetes duration, blood pressure, lipids or glycaemic
      control between the four groups of pedometer-determined physical activity.
      Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m(2), P < 0.001),
      waist circumference (101.7 vs. 108.0 cm, P < 0.001), lower levels of C-reactive
      protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8
      pg ml, P < 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009)
      compared with less physically active people. CONCLUSIONS: We conclude that
      physical activity measured with pedometer was associated not only with less
      abdominal obesity, but also with decreased systemic low-grade inflammation as
      well as with low arterial stiffness, in people with Type 2 diabetes.

PMID- 22364115
TI  - Informed consent: are researchers accurately representing risks and benefits?
AB  - Changes in the scope of health research in the last 50 years require evidence to
      support assumptions about what constitutes harm and benefit to research
      participants. The aim of this study was to investigate the actual benefits and
      harm individuals experienced while participating in potentially distressing
      qualitative research. Data were collected via semi-structured interviews and
      subjected to thematic analysis. Five themes emerged: (i) motivation to
      participate, (ii) expectations of participation, (iii) sources of harm, (iv)
      mitigating harm and (v) benefits of participation. Results indicated that all
      participants benefited through participation in the qualitative research. Most
      participants also reported varying degrees of distress during the interviews, but
      did not consider this harmful. In contrast, dissemination of the findings did
      constitute an unexpected source of potential harm for the participants and
      researcher. It is concluded that for these participants, distress during
      qualitative interviewing is not in itself harmful, and that participant
      information sheets need to reflect the harms and benefits of participation more
      accurately in a user-friendly format. Furthermore, the sensitivity with which
      research is disseminated needs to be considered as a fundamental protection for
      participants from unwarranted criticism by third parties. Recommendations include
      that researchers conducting interviews have specific personal and professional
      attributes relevant to the participant group, and that transcripts/raw data
      should not be sent automatically to participants.

PMID- 22364116
TI  - Bringing trees into the fuel line.

PMID- 22364117
TI  - Learning from the past: how low [CO2] studies inform plant and ecosystem response
      to future climate change.

PMID- 22364118
TI  - Evidence that sphingolipid signaling is involved in responding to low
      temperature.

PMID- 22364119
TI  - Dew, where and when? 'There are more things in heaven and earth, Horatio, than
      are dreamt of in your philosophy '...

PMID- 22364120
TI  - Gold derivatives of eight rare-earth-metal-rich tellurides: monoclinic R7Au2Te2
      and orthorhombic R6AuTe2 types.
AB  - Two series of rare-earth-metal (R) compounds, R(7)Au(2)Te(2) (R = Tb, Dy, Ho) and
      R(6)AuTe(2) (R = Sc, Y, Dy, Ho, Lu), have been synthesized by high-temperature
      techniques and characterized by X-ray diffraction analyses as monoclinic
      Er(7)Au(2)Te(2)-type and orthorhombic Sc(6)PdTe(2)-type structures, respectively.
      Single-crystal diffraction results are reported for Ho(7)Au(2)Te(2),
      Lu(6)AuTe(2), Sc(6)Au(0.856(2))Te(2), and Sc(6)Au(0.892(3))Te(2). The structure
      of Ho(7)Au(2)Te(2) consists of columns of Au-centered tricapped trigonal prisms
      (TCTPs) of Ho condensed into 2D zigzag sheets that are interbridged by Te and
      additional Ho to form the 3D network. The structure of Lu(6)AuTe(2) is built of
      pairs of Au-centered Lu TCTP chains condensed with double Lu octahedra in chains
      into 2D zigzag sheets that are separated by Te atoms. Tight binding-linear muffin
      tin orbital-atomic sphere approximation electronic structure calculations on
      Lu(6)AuTe(2) indicate a metallic property. The principal polar Lu-Au and Lu-Te
      interactions constitute 75% of the total Hamilton populations, in contrast to the
      small values for Lu-Lu bonding even though these comprise the majority of the
      atoms. A comparison of the theoretical results for Lu(6)AuTe(2) with those for
      isotypic Lu(6)AgTe(2) and Lu(6)CuTe(2) provides clear evidence of the greater
      relativistic effects in the bonding of Au. The parallels and noteworthy contrasts
      between Ho(7)Au(2)Te(2) (35 valence electrons) and the isotypic but much electron
      richer Nb(7)P(4) (55 valence electrons) are analyzed and discussed.

PMID- 22364121
TI  - Successful treatment with pulse cyclophosphamide of a steroid-refractory
      hepatitic variant of liver acute graft-vs.-host disease in a child.
AB  - A 13-yr-old boy with recurrent acute myeloid leukemia underwent HSCT using cells
      from an unrelated donor who matched all HLA antigens except one. Forty-two days
      later, the patient developed a steroid-refractory hepatitic variant of liver GVHD
      with peak ALT and T.Bil values of 1406 mU/mL and 10.4 mg/dL, respectively. He was
      successfully treated with pulse Cy (1000 mg/dose * one day) without a change in
      chimerism being observed or acquiring an infection. All immunosuppressant
      therapies could be discontinued 12 months after HSCT. Two yr after HSCT, the
      patient remains in CR without chronic GVHD. This single case report suggests that
      pulse Cy may be a promising therapy for steroid-refractory GVHD, especially
      hepatitic GVHD, but needs to be further tested in clinical trials.

PMID- 22364122
TI  - Demonstration of antioxidant and anti-inflammatory bioactivities from sugar-amino
      acid maillard reaction products.
AB  - Maillard reaction products (MRPs), both crude and fractionated, were assessed for
      antioxidant potential using cell-free, in vitro 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical scavenging, Fenton reaction induced deoxyribose degradation and
      oxygen radical absorbance capacity-fluorescein (ORACFL) chemical assays. All MRPs
      displayed various affinities to scavenge free radicals generated in different
      reaction media and using different reactive oxygen species (ROS) substrates. High
      molecular weight MRPs consistently showed the greatest (P < 0.05) antioxidant
      potential in chemical assays. Repeating these tests in Caco-2 cells with both
      reactive oxygen and nitrogen (RNS) intracellular assays revealed that the low
      molecular weight components (LMW) were most effective at inhibiting oxidation and
      inflammation. In particular, a glucose-lysine (Glu-Lys) mixture heated for 60 min
      had marked intracellular antioxidant activity and nitric oxide (NO) and
      interleukin-8 (IL-8) inhibitory activities compared to other MRPs (P < 0.05).
      Further studies employing ultrafiltration, ethyl acetate extraction, and
      semipreparative high-performance liquid chromatography (HPLC) produced a
      bioactive fraction, termed F3, from heated Glu-Lys MRP. F3 inhibited NO,
      inducible nitric oxide synthetase (iNOS), and IL-8 in interferon gamma (IFN
      gamma)- and phorbol ester (PMA)-induced Caco-2 cells. F3 modified several gene
      expressions involved in the NF-kappaB signaling pathway. Two components, namely,
      5-hydroxymethyl-2-furfural (HMF) and 5-hydroxymethyl-2-furoic acid (HMFA), were
      identified in the F3 fraction, with an unidentified third component comprising a
      major portion of the bioactivity. The results show that MRP components have
      bioactive potential, especially in regard to suppressing oxidative stress and
      inflammation in IFN-gamma- and PMA-induced Caco-2 cells. 

PMID- 22364123
TI  - Antimicrobial activity of polyphenol-rich fractions from Sida alba L. (Malvaceae)
      against co-trimoxazol-resistant bacteria strains.
AB  - BACKGROUND: The increased resistance of microorganisms to the currently used
      antimicrobials has lead to the evaluation of other agents that might have
      antimicrobial activity. Medicinal plants are sources of phytochemicals which are
      able to initiate different biological activities including antimicrobials
      MATERIALS AND METHODS: In vitro antibacterial (MIC, MBC and time-kill studies) of
      polyphenol-rich fractions from Sida alba L. (Malvaceae) was assessed using ten
      bacteria strains (Gram-negative and Gram-positive). RESULTS: All test bacteria
      were susceptible to the polyphenol-rich fractions. Time-kill results showed that
      after 5 h exposition there was no viable microorganism in the initial inoculum
      and the effect of polyphenol-rich fractions was faster on Enterococcus faecalis
      (Gram-positive bacterium) comparatively to the other bacteria strains.
      CONCLUSION: The data analysis indicates that the tested of polyphenol-rich
      fractions has significant effects when compared with the standard antibiotic.
      These results therefore justify the traditional use of sida alba L., alone or in
      combination with other herbs to treat bacterial infections.

PMID- 22364124
TI  - Effects of 420-nm intense pulsed light in an acne animal model.
AB  - BACKGROUND: Blue light in the 400-420 nm range has been shown to reduce the
      levels of Propionibacterium acnes (P. acnes) in the skin. P. acnes has been
      postulated to be a critical trigger for inflammatory acne. Thus, treatment with
      420 nm-intense pulsed light should reduce inflammatory activity in acne. AIM: To
      evaluate the clinical and histological effects of 420 nm-intense pulsed light
      treatment on acne in animal model. METHOD: Inflammation acne animal model was
      constructed by intradermal injection of P. acnes of rat auricular. Levels of
      tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 2 (MMP-2),
      markers of inflammation implicated in acne, were assessed in treated and
      untreated animals by immunohistochemistry and quantitative polymerase chain
      reaction (PCR). RESULT: Treatment with 420 nm intense pulsed light led to marked
      improvement after 6 biweekly treatments. Immunohistochemistry and PCR showed that
      TNF-alpha and MMP-2 levels correlated with the extent of acneiform activity and
      were reduced by treatment with 420 nm light. CONCLUSION: A 420-nm intense pulsed
      light may exert its beneficial effects on inflammatory acne by reducing the
      levels of P. acnes and secondarily reducing inflammation induced by the bacteria.

PMID- 22364125
TI  - Evidence for selection at cytokine loci in a natural population of field voles
      (Microtus agrestis).
AB  - Individuals in natural populations are frequently exposed to a wide range of
      pathogens. Given the diverse profile of gene products involved in responses to
      different types of pathogen, this potentially results in complex pathogen
      specific selection pressures acting on a broad spectrum of immune system genes in
      wild animals. Thus far, studies into the evolution of immune genes in natural
      populations have focused almost exclusively on the Major Histocompatibility
      Complex (MHC). However, the MHC represents only a fraction of the immune system
      and there is a need to broaden research in wild species to include other immune
      genes. Here, we examine the evidence for natural selection in a range of non-MHC
      genes in a natural population of field voles (Microtus agrestis). We concentrate
      primarily on genes encoding cytokines, signalling molecules critical in eliciting
      and mediating immune responses and identify signatures of natural selection
      acting on several of these genes. In particular, genetic diversity within
      Interleukin 1 beta and Interleukin 2 appears to have been maintained through
      balancing selection. Taken together with previous findings that polymorphism
      within these genes is associated with variation in resistance to multiple
      pathogens, this suggests that pathogen-mediated selection may be an important
      force driving genetic diversity at cytokine loci in voles and other natural
      populations. These results also suggest that, along with the MHC, preservation of
      genetic variation within cytokine genes should be a priority for the conservation
      genetics of threatened wildlife populations.

PMID- 22364126
TI  - Structural and functional evolution of the translocator protein (18 kDa).
AB  - Translocator proteins (TSPO) are the products of a family of genes that is
      evolutionarily conserved from bacteria to humans and expressed in most mammalian
      tissues and cells. Human TSPO (18 kDa) is expressed at high levels in steroid
      synthesizing endocrine tissues where it localizes to mitochondria and functions
      in the first step of steroid formation, the transport of cholesterol into the
      mitochondria. TSPO expression is elevated in cancerous tissues and during tissue
      injury, which has lead to the hypothesis that TSPO has roles in apoptosis and the
      maintenance of mitochondrial integrity. We recently identified a new paralog of
      Tspo in both the human and mouse. This paralog arose from an ancient gene
      duplication event before the divergence of the classes aves and mammals, and
      appears to have specialized tissue-, cell-, and organelle-specific functions.
      Evidence from the study of TSPO homologs in mammals, bacteria, and plants
      supports the conclusion that the TSPO family of proteins regulates specialized
      functions related to oxygen-mediated metabolism. In this review, we provide a
      comprehensive overview of the divergent function and evolutionary origin of Tspo
      genes in Bacteria, Archaea, and Eukarya domains.

PMID- 22364127
TI  - The 18 kDa translocator protein (TSPO): a new perspective in mitochondrial
      biology.
AB  - In mammals, mitochondria are central in maintaining normal cell function and
      dissecting the pathways that govern their physiology and pathology is therefore
      of utmost importance. For a long time, the science world has acknowledged the
      Translocator Protein (TSPO), an intriguing molecule that, through its position
      and association with biological processes, stands as one of the hidden regulatory
      pathways in mitochondrial homeostasis. Here we aim to review the literature and
      highlight what links TSPO to mitochondrial homeostasis in order to delineate its
      contribution in the functioning and malfunctioning of this critical organelle. In
      detail, we will discuss: 1) TSPO localization and interplay with controlling
      phenomena of mitochondria (e.g. mPTP); 2) TSPO interaction with the prominent
      mitochondrial player VDAC; consider evidence on how TSPO relates to 3)
      mitochondrial energy production; 4) Ca2+ signalling and 5) the generation of
      Reactive Oxygen Species (ROS) before finally describing 6) its part in apoptotic
      cell death. In essence, we hope to demonstrate the intimate involvement TSPO has
      in the regulation of mitochondrial homeostasis and muster attention towards this
      molecule, which is equally central for both cellular and mitochondrial biology.

PMID- 22364128
TI  - Role of translocator protein in renal ischemia reperfusion, renal preservation
      and acute kidney injury.
AB  - Translocator protein (TSPO), formerly known as peripheral-type benzodiazepine
      receptor (PBR), has been described in several tissues and characterized as one of
      the main elements of steroidogenesis. However, TSPO is also involved in other
      pathways and cell functions, such as apoptosis regulation, protein import,
      membrane biogenesis, cell cycle regulation, oxygen homeostasis and mitochondrial
      membrane fluidity regulation. In the kidney, TSPO is normally located in the
      distal parts of the nephron from the thick ascending limb of the loop of Henle to
      the medullary collecting ducts. However when the kidney is submitted to a stress
      such as ischemia reperfusion injury there is a defined change in TSPO expression
      towards more proximal areas of the nephron, and the protein can be detected as
      high as proximal tubular cells and the Bowman Capsule. As the injury persists,
      TSPO is also located in invading mononucleated cells, in a pattern reproducing
      invasion by CD4+ helper T cells, and in the damaged vessels where TSPO is
      expressed both in endothelial and smooth muscle cells. Herein we review the
      potential use of TSPO-directed treatment for ischemia reperfusion injury,
      particularly regarding pre-conditioning of the organ. We also detail the
      relationship of proximal TSPO staining with the intensity of the injury,
      particularly the implication of monomeric (18 kDa) TSPO and its role in hypoxia
      reoxygenation and apoptosis prevention. The potential implications of the protein
      with regeneration processes activated in response to injury and their relation
      with embryogenesis pathways are discussed.

PMID- 22364129
TI  - Rheumatoid arthritis: cardiovascular manifestations, pathogenesis, and therapy.
AB  - Rheumatoid Arthritis (RA) is a chronic progressive inflammatory joint disorder
      that affects 0.5% - 1% of the general population. This review article discusses
      cardiovascular manifestations of rheumatoid arthritis, pathogenesis of these
      manifestations, and therapy. This disease not only affects the joints, but it
      also involves other organ systems. The majority of these patients suffer
      significant morbidity and mortality from cardiovascular disease. Cardiovascular
      manifestations of RA include predilection for accelerated atherosclerosis and
      endothelial dysfunction resulting in coronary artery disease (CAD), stroke,
      congestive heart failure, and peripheral arterial disease. Some studies have
      shown that the risk of developing CAD in RA patients is the same as for patients
      with diabetes mellitus. These patients should be treated with aggressive medical
      therapy such as disease modifying antirheumatic drugs, tumor necrosis factor
      alpha inhibitors, and corticosteroids and with appropriate control of risk
      factors such as smoking, dyslipidemia, hypertension, and obesity. Other
      manifestations include pericarditis, myocarditis, and vasculitis.

PMID- 22364130
TI  - Systemic sclerosis-related pulmonary hypertension: unique characteristics and
      future treatment targets.
AB  - Pulmonary arterial hypertension (PAH) is a severe vascular complication of
      connective tissue diseases. In the context of systemic sclerosis (SSc), PAH is a
      devastating disease with a dramatic impact on prognosis and survival. Despite
      advances in early diagnosis and the development of new targeted treatments, SSc
      related pulmonary arterial hypertension (SScPAH) represents the leading cause of
      death in SSc patients with reported poorer response in therapy and worse
      prognosis compared with idiopathic PAH. Recent findings indicate that factors
      accounting for these differences may include cardiac involvement, pronounced
      autoimmune and inflammatory response and pulmonary venous vasculature remodeling.
      Deeper understanding of the underlying pathogenic mechanisms of pulmonary
      vascular disorders in SScPAH may lead to novel therapeutic strategies which are
      currently under investigation and may improve the outcome of these patients, for
      whom our therapeutic armamentarium is not effective enough. In this article we
      attempt to critically analyze the factors contributing to the unique phenotype of
      SScPAH focusing on future challenges for the design of novel targeted treatments
      which may alter the natural history of the disease.

PMID- 22364131
TI  - Excess cardiovascular risk in inflammatory rheumatic diseases: pathophysiology
      and targeted therapy.
AB  - The article reviews the evidence and extent of the excess cardiovascular risk in
      patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and
      ankylosing spondylitis. RA entails nearly twice as high a standardized mortality
      ratio and is considered an equivalent of type 2 diabetes with regard to
      cardiovascular risk. The associated excess cardiovascular risk can only partly be
      explained by traditional risk factors, and the underlying inflammation is
      crucially involved in the pathogenesis.  Data obtained from patients with early
      RA suggest that serum triglycerides, a proxy of disease activity as markers of
      systemic inflammation, impaired function of apolipoprotein A-I and HDL particles,
      and mediating hypertension are determinants of the excess cardiovascular risk.
      These changes seem to be preceded by a lowering of total cholesterol and are
      followed in the course of the disease by immune processes typically illustrated
      by positivity of rheumatoid factor. Evidence is available to postulate the notion
      that reduced plasma lipoprotein- associated phospholipaseA2 mass or activity,
      mediated by diminished hydrolysis of VLDL triglycerides and of Lp(a)
      phospholipids, may induce reduction or altered composition of HDL particles and
      apoA-I dysfunction which, along with elevated plasma triglycerides, initiate and
      contribute to chronic inflammation.  Lifestyle modification, traditional non
      steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors, low-dose
      corticosteroids, statins, tumor-necrosis-alpha inhibitors and, particularly, the
      immunosuppressive methotrexate, all have potential beneficial effects in
      eliciting a reduction in disease activity and cardiovascular risk. Adherence to
      the recent EULAR recommendations is a key in the prevention and management of
      cardiovascular risk among patients with rheumatic diseases.

PMID- 22364132
TI  - Inflammation-induced thrombosis: mechanisms, disease associations and management.
AB  - Although inflammation-induced thrombosis is a well-known entity, its pathogenesis
      remains complicated. There are complex interactions between inflammation and
      hemostasis, involving proinflammatory cytokines, chemokines, adhesion molecules,
      tissue factor expression, platelet and endothelial activation, and
      microparticles. Inflammation increases procoagulant factors, and also inhibits
      natural anticoagulant pathways and fibrinolytic activity, causing a thrombotic
      tendency. Besides, chronic inflammation may cause endothelial damage, resulting
      in the loss of physiologic anticoagulant, antiaggregant and vasodilatory
      properties of endothelium. However, inflammation- induced venous thrombosis may
      develop even in the absence of vessel wall damage. On the other hand, coagulation
      also augments inflammation, causing a vicious cycle. This is mainly achieved by
      means of thrombin-induced secretion of proinflammatory cytokines and growth
      factors. Platelets may also trigger inflammation by activating the dendritic
      cells.  There are many systemic inflammatory diseases characterized by thrombotic
      tendency, including Behcet disease (BD), antineutrophilic cytoplasmic antibody
      associated vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus
      erythematosus, antiphosholipid syndrome, familial Mediterranean fever,
      thromboangiitis obliterans (TAO) and inflammatory bowel diseases.  Inflammation
      induced thrombosis may respond to immunosuppressive (IS) treatment, as in the
      case of BD. However effectiveness of this treatment can not be generalized to all
      other inflammatory diseases. For instance, IS agents do not have any beneficial
      role in the management of TAO. Heparin, antiplatelet agents such as aspirin and
      clopidogrel, colchicine and statins also have some antiinflammatory activity.
      However, decreased responsiveness to aspirin and clopidogrel treatments may be
      observed in inflammatory diseases, due to antiplatelet resistance caused by
      systemic inflammation.  In the present review, we aimed to discuss the details of
      the complex crosstalk between inflammation and hemostasis in the context of
      available data. We also intended to overview the major inflammatory diseases with
      thrombotic tendency, as well as to discuss the general principles of the
      management of inflammation-induced thrombosis.

PMID- 22364133
TI  - Inflammation and vascular responses to acute mental stress: implications for the
      triggering of myocardial infarction.
AB  - There is evidence that mental stress can trigger myocardial infarction. Even
      though the underlying mechanisms remain to be determined, both inflammation and
      vascular responses to mental stress have been implicated as contributing factors.
      This review explores the effects of inflammation on the vascular responses to
      mental stress. First, the associations between inflammation and resting vascular
      function are discussed. It is known that increases in inflammation are associated
      with endothelial dysfunction, with a reduction in nitric oxide a common pathway
      through which inflammation can influence endothelial function. Second, the
      effects of mental stress on vascular responses are reviewed. There is ample
      evidence that in healthy participants, mental stress induces increases in forearm
      blood flow, which is impaired in those at risk for cardiovascular disease. Even
      though several mechanisms are discussed, there is evidence that nitric oxide
      plays an important role in stress-induced vasodilation. Finally, the influences
      of inflammation on the vascular responses are described. It is hypothesised that
      inflammation can alter vascular responses to mental stress, most likely due to
      lower levels of nitric oxide as a result of the inflammation. This poorer
      vascular response is thought to be an underlying factor through which mental
      stress can trigger myocardial infarction.

PMID- 22364134
TI  - The effects of tumor necrosis factor inhibitors on cardiovascular risk in
      rheumatoid arthritis.
AB  - There is abundant evidence that rheumatoid arthritis (RA), a chronic inflammatory
      disorder, is associated with an increased risk for cardiovascular (CV) disease.
      While there may be several mechanisms contributing to a higher CV risk in RA
      patients, inflammation is considered to be the main cause explaining the excess
      CV burden. Inflammatory processes appear pivotal to the atherothrombotic process
      and are linked to endothelial dysfunction, fatty streak initiation and
      progression, deterioration of fatty streaks into (unstable) plaques, and plaque
      rupture. Moreover, systemic inflammation, through tumor necrosis factor (TNF) or
      related cytokines, appears to accelerate atherothrombosis either directly or via
      effects on conventional and novel CV risk factors, such as lipids and
      lipoproteins, blood pressure, haemostatic factors, and insulin resistance. New
      and highly specific therapeutic agents (TNF inhibitors) may significantly lower
      CV risk in RA. This review summarizes the evidence base supporting the notion
      that TNF inhibitors confer benefit CV disease risk in RA.

PMID- 22364135
TI  - The effect of anti-B-cell therapy on the development of atherosclerosis in
      patients with rheumatoid arthritis.
AB  - Accelerated development of atherosclerosis (AT) in rheumatoid arthritis (RA)
      stems from common immune-inflammatory mechanisms underlying the diseases. While
      the key role of activation of the T-cell immune system component is considered to
      be proved, the role of B-lymphocytes has been investigated insufficiently.
      Earlier experimental models demonstrated the "atheroprotective" role of B-cells.
      At the same time, AT development is associated with activation of the B-cell
      immune system component and manifested by hyperproduction of antibodies to
      oxidized low density lipoproteins (oxLDL), heat shock proteins, etc. Wide
      applications of anti-B-cell therapy stimulate active research on effects of B
      lymphocytes and their depletion on AT development in RA patients that have a high
      risk of cardiovascular events (CVE). Experimental models demonstrated that
      depletion of B2 cells instead of B1 cells under anti-CD20 treatment resulted in a
      slower development and progression of AT. Research on cardiovascular effects of
      chimeric antiCD20 monoclonal antibody (rituximab, RTX) in RA is definitely of
      high interest. Use of RTX in a combination with methotrexate does not increase
      the risk of serious side effects, including CVE, compared with the sole use of
      methotrexate. Currently, only few pilot research reports on favorable effects of
      RTX on the lipid profile and endothelial function in RA patients have been
      published. According to other authors, the frequency of CVE in RA patients
      receiving RTX therapy was somewhat higher than that in patients not treated with
      RTX. In rare cases such side effects as hypotension and arrhythmia were reported
      under RTX infusion. In addition, investigation of the combined use of statins and
      RTX is important, since some data are available on a reduced efficacy of RTX when
      administered with statins. Therefore, further research is required to clarify the
      role of the B-cell immune system component in AT development and the impact of
      anti-B cell therapy on the pathogenetic mechanisms of AT and CVE in RA patients.

PMID- 22364137
TI  - Marine n-3 fatty acids for cardiovascular risk reduction and disease control in
      rheumatoid arthritis: "kill two birds with one stone"?
AB  - Rheumatoid arthritis (RA), the most common chronic systemic inflammatory disease
      leading to joint destruction and disability, is associated with increased
      cardiovascular mortality. Systemic inflammation and increased burden of
      traditional cardiovascular risk factors present in RA are currently considered
      responsible for the accelerated atherosclerosis in these patients. Herein, we
      highlight a potential double effect of dietary intake of the n-3 long-chain
      polyunsaturated fatty acids (LCP) eicosapentaenoic acid (EPA; 20:5n-3) and
      docosahexaenoic acid (DHA; 22:6n-3) on cardiovascular risk reduction and disease
      control in patients with RA. Large studies in non-RA populations provide strong
      evidence for the beneficial effect of n-3 LCP supplementation in primary and
      secondary cardiovascular prevention. Cardiovascular risk reduction is at least
      partly explained by n-3 LCP effects on blood pressure, dyslipidemia, thrombosis
      and inflammation, all important factors also in RA, whereas abnormalities in
      vascular function and in vascular morphology similar to those observed in RA
      patients may even be moderately reversed. On the other hand, there is evidence
      from 6 of 14 randomized controlled trials supporting a favorable effect of n-3
      LCP supplementation in decreasing joint inflammation in RA. Although specific
      studies in RA patients are currently lacking, a double beneficial effect of n-3
      LCP seems likely. The size of any such effect and how it compares with other
      interventions such as lifestyle changes, biologic therapies, and statin therapy,
      needs to be investigated prospectively in carefully designed studies.

PMID- 22364138
TI  - Adverse cardiovascular effects of antirheumatic drugs: implications for clinical
      practice and research.
AB  - Clinical manifestations of most rheumatic diseases have changed over the past few
      decades, largely due to advances in therapies targeting autoimmune and
      (auto)inflammatory pathways. Improvements in the management of rheumatic diseases
      have also now brought to the fore the issue of comorbidities. It has become
      evident that the burden of cardiovascular morbidity and mortality is increased in
      rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and the
      spondyloarthropathies, amongst other conditions. As a result, efforts have
      switched toward investigating the effects of conventional antirheumatic and new
      biologic agents on inflammationinduced atherothrombosis. Evidence is accumulating
      suggesting a beneficial cardiovascular profile of some antirheumatic drugs, such
      as methotrexate and hydroxychloroquine, but it also indicates the possibility of
      a variety of adverse events developing in the short- and long-term. The aim of
      this review is to highlight cardiovascular adverse effects of the drugs widely
      used in the treatment of rheumatic diseases. The literature search was performed
      through PubMed, the Cochrane Library, Scopus, and Web of Science databases using
      the following terms: "antirheumatic drugs", "inflammation", "rheumatic diseases",
      "cardiovascular diseases", "adverse events", "toxicity", "drug design", and "drug
      interactions". Adverse events ranging from infusion-related hypertension and
      myocardial ischemia, to restrictive cardiomyopathy and congestive heart failure
      have been reported in large trials and case series on most antirheumatic drugs.
      Clinicians should be alert of the wide variety of cardiovascular adverse effects
      of individual antirheumatic drugs, and should carefully monitor blood pressure
      and markers of inflammation, thrombosis, myocardial ischemia, electrolytes, and
      lipid disturbances while administering these drugs. Future prospective studies
      should specifically investigate the cardiovascular safety of most antirheumatic
      drugs as part of mono- or combination therapy in relation to different dosage
      regimens, duration of therapy, age, and gender.

PMID- 22364139
TI  - Cardiovascular risk and inflammation: pathophysiological mechanisms, drug design,
      and targets.

PMID- 22364136
TI  - Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and
      lessons from the recent clinical trials.
AB  - Ample evidence exists in support of the potent anti-inflammatory properties of
      statins. In cell studies and animal models statins exert beneficial
      cardiovascular effects. By inhibiting intracellular isoprenoids formation,
      statins suppress vascular and myocardial inflammation, favorably modulate
      vascular and myocardial redox state and improve nitric oxide bioavailability.
      Randomized clinical trials have demonstrated that further to their lipid lowering
      effects, statins are useful in the primary and secondary prevention of coronary
      heart disease (CHD) due to their anti-inflammatory potential. The landmark
      JUPITER trial suggested that in subjects without CHD, suppression of low-grade
      inflammation by statins improves clinical outcome. However, recent trials have
      failed to document any clinical benefit with statins in high risk groups, such in
      heart failure or chronic kidney disease patients. In this review, we aim to
      summarize the existing evidence on statins as an anti-inflammatory agent in
      atherogenesis. We describe the molecular mechanisms responsible for the
      antiinflammatory effects of statins, as well as clinical data on the non lipid
      lowering, anti-inflammatory effects of statins on cardiovascular outcomes.
      Lastly, the controversy of the recent large randomized clinical trials and the
      issue of statin withdrawal are also discussed.

PMID- 22364140
TI  - Validation of an unlabeled probe melting analysis assay combined with high
      throughput extractions for genotyping of the most common variants in HFE
      associated hereditary hemochromatosis, C282Y, H63D, and S65C.
AB  - Hereditary hemochromatosis is an inherited disorder of iron metabolism,
      characterized by high absorption of iron by the gastrointestinal tract leading to
      a toxic accumulation of iron in various organs and impaired organ function. Three
      variants in the HFE gene (p.C282Y, p.H63D, and p.S65C) are commonly associated
      with the development of the disease. Of these, p.C282Y homozygotes are at the
      highest risk. Compound heterozygotes of p.C282Y along with p.H63D or p.S65C have
      reduced penetrance. Furthermore, p.H63D homozygotes are not at an increased risk
      and little is known about the risk associated with homozygocity for p.S65C. Our
      current clinical assay for the three common HFE variants utilizes the LightCycler
      platform and paired probes employing fluorescent resonance energy transfer. To
      increase throughput and decrease costs, we developed a method whereby automated
      extraction was combined with unlabeled probes and differential melt profiles to
      detect these variants using the LightCycler 480 instrument. Using this approach,
      43 samples extracted with three different extraction platforms were correctly
      genotyped. These data demonstrate that the newly developed assay to genotype the
      HFE mutations p.C282Y, p.H63D, and p.S65C, combined with high-throughput
      extraction platforms, is accurate and reproducible and represents an alternative
      to previously described tests.

PMID- 22364142
TI  - Intensifying insulin therapy with insulin analog premixes: transitioning from
      basal insulin in type 2 diabetes.
AB  - Because of the progressive nature of type 2 diabetes, basal insulin alone may not
      be able to provide sufficient glycemic control over the long term, and thus
      insulin regimens will typically need to be intensified--especially for
      controlling postprandial glucose excursions. In patients with type 2 diabetes
      requiring more intensive intervention, insulin analog premix formulations can
      offer a simple, effective, and convenient option for tighter management of
      hyperglycemia in lieu of a traditional basal-bolus regimen.

PMID- 22364141
TI  - A switch in therapy to a reverse transcriptase inhibitor sparing combination of
      lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected
      patients: a pilot randomized trial to assess efficacy and safety profile: the
      KITE study.
AB  - A nucleoside reverse transcriptase inhibitor (NRTI) backbone is a recommended
      component of standard highly active antiretroviral therapy (sHAART). However,
      long-term NRTI exposure can be limited by toxicities. NRTI class-sparing
      alternatives are warranted in select patient populations. This is a 48-week
      single-center, open-label pilot study in which 60 HIV-infected adults with plasma
      HIV-1 RNA (<50 copies/ml) on sHAART were randomized (2:1) to lopinavir/ritonavir
      (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch (LPV-r/RAL arm) or to
      continue on sHAART. The primary endpoint was the proportion of subjects with HIV
      RNA<50 copies/ml at week 48. Secondary efficacy and immunologic and safety
      endpoints were evaluated. Demographics and baseline lipid profile were similar
      across arms. Mean entry CD4 T cell count was 493 cells/mm(3). At week 48, 92%
      [95% confidence interval (CI): 83-100%] of the LPV-r/RAL arm and 88% (95% CI: 75
      100%) of the sHAART arm had HIV-RNA<50 copies/ml (p=0.70). Lipid profile (mean +/
      SEM, mg/dl, LPV-r/RAL vs. sHAART) at week 24 was total-cholesterol 194 +/- 5 vs.
      176 +/- 9 (p=0.07), triglycerides 234 +/- 30 vs. 133 +/- 27 (p=0.003), and LDL
      cholesterol 121 +/- 6 vs. 110 +/- 8 (p=0.27). There were no serious adverse
      events (AEs) in either arm. Regimen change occurred in three LPV-r/RAL subjects
      (n=1, due to LPV-r/RAL-related AEs) vs. 0 in sHAART. There were no differences
      between arms in bone mineral density, total body fat composition, creatinine
      clearance, or CD4 T cell counts at week 48. In virologically suppressed patients
      on HAART, switching therapy to the NRTI-sparing LPV-r/RAL combination produced
      similar sustained virologic suppression and immunologic profile as sHAART. AEs
      were comparable between arms, but the LPV-r/RAL arm experienced higher
      triglyceridemia.

PMID- 22364143
TI  - U-500 insulin as a component of basal bolus insulin therapy in type 2 diabetes.
AB  - BACKGROUND: Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose
      (TDD) were investigated following initiation of insulin U-500 (U500) alone or as
      part of a basal/bolus insulin (BBI) regimen. SUBJECTS AND METHODS: Records of
      patients with type 2 diabetes who were prescribed U500 were retrospectively
      reviewed. Logistic regression analysis was used to investigate relationships
      between changes in A1C and use of U500 alone or as BBI. RESULTS: Twelve patients
      were identified as using U500 alone (n=2) or in combination with long-acting
      (LAI) (n=7) or rapid-acting (RAI) (n=3) insulin. Reductions in A1C (9.5% at
      baseline vs. 7.7% at 6-9 months, P<0.0001) and increases in weight (128.8+/-32.7
      vs. 131.5+/-31.3 kg, P<0.014) and TDD (260+/-111 to 333+/-106 units/day,
      P<0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict
      improvements in A1C. CONCLUSIONS: U500 resulted in improvements in A1C and weight
      gain and increased TDD when used alone or as part of combination insulin therapy.
      Further investigations to define the optimal use of U500 are recommended.

PMID- 22364144
TI  - Activity as a tool in language training for immigrants and refugees.
AB  - OBJECTIVE: The focus of this study is how skills acquired from everyday life in
      one's native country can represent a resource in language training and work for
      immigrants and refugees. The specific aim is to explore what significance
      activity and participation in activity have on language training. METHODS: This
      qualitative study is based on fieldwork carried out in relation to a group of
      illiterate immigrants at a centre for adult education. The sample consists of 11
      adult immigrants and refugees, male and female, between the ages of 20 and 65.
      The interviews with all the participants were carried out with the help of an
      interpreter. RESULTS: The main findings were that the individual immigrant's
      history of activities received little attention during the language training.
      There was hardly any mention of previous experience from everyday life and work.
      By relying on different activities in the language training, the resources and
      background of the individual immigrant would have become more visible. Familiar
      activities from one's own culture enable communication when language skills are
      limited.

PMID- 22364145
TI  - Who are you looking at? The influence of face gender on visual attention and
      memory for own- and other-race faces.
AB  - Previous research suggests that the own-race bias (ORB) in memory for faces is a
      result of other-race faces receiving less visual attention at encoding. As women
      typically display an own-gender bias in memory for faces and men do not, we
      investigated whether face gender and sex of viewer influenced visual attention
      and memory for own- and other-race faces, and if preferential viewing of own-race
      faces contributed to the ORB in memory. Participants viewed pairs of female or
      male own- and other-race faces while their viewing time was recorded. Afterwards,
      they completed a surprise memory test. We found that (1) other-race males
      received the initial focus of attention, (2) own-race faces were viewed longer
      than other-race faces over time, although the difference was larger for female
      faces, and (3) even though longer viewing time increased the probability of
      remembering a face, it did not explain the magnified ORB in memory for female
      faces. Importantly, these findings highlight that face gender moderates
      attentional responses to and memory for own- and other-race faces.

PMID- 22364147
TI  - A switchable molecular rotator: neutron spectroscopy study on a polymeric spin
      crossover compound.
AB  - A quasielastic neutron scattering and solid-state (2)H NMR spectroscopy study of
      the polymeric spin-crossover compound {Fe(pyrazine)[Pt(CN)(4)]} shows that the
      switching of the rotation of a molecular fragment--the pyrazine ligand--occurs in
      association with the change of spin state. The rotation switching was examined on
      a wide time scale (10(-13)-10(-3) s) by both techniques, which clearly
      demonstrated the combination between molecular rotation and spin-crossover
      transition under external stimuli (temperature and chemical). The pyrazine rings
      are seen to perform a 4-fold jump motion about the coordinating nitrogen axis in
      the high-spin state. In the low-spin state, however, the motion is suppressed,
      while when the system incorporates benzene guest molecules, the movements of the
      system are even more restricted.

PMID- 22364148
TI  - Review of rate constants and exploration of correlations of the halogen transfer
      reaction of trisubstituted carbon-centered radicals with molecular halogens.
AB  - Rate constants for the reaction (R'(3)C(*) + X(2) -> R'(3)CX + X(*); X = F, Cl,
      Br, I) are reviewed. Because of curved Arrhenius plots and negative E(X) values,
      empirical structure-reactivity correlations are sought for log k(X,298) rather
      than E(X). The well-known poor correlation with measures of reaction enthalpy is
      demonstrated. The best quantitative predictor for R'(3)C(*) is Sigmasigma(p), the
      sum of the Hammett sigma(p) constants for the three substituents, R'.
      Electronegative substituents with lone pairs, such as halogen and oxygen, thus
      appear to destabilize the formation of a polarized prereaction complex and/or TS
      ((delta+)R- - -X- - -X(delta-)) by sigma inductive/field electron withdrawal
      while simultaneously stabilizing them by pi resonance electron donation. The best
      quantitative predictor of the reactivity order of the halogens, I(2) > Br(2) ?
      Cl(2) ~ F(2), is the polarizability of the halogen, alpha(X(2)). For the data set
      of 60 rate constants which span 6.5 orders of magnitude, a modestly successful
      correlation of log k(X,298) is achieved with only two parameters, Sigmasigma(p)
      and alpha(X(2)), with a mean unsigned deviation of 0.59 log unit. How much of
      this residual variance is the result of inaccuracies in the data in comparison
      with oversimplification of the correlation approach remains to be seen.

PMID- 22364149
TI  - Affinity of two novel five-coordinated anticancer Pt(II) complexes to human and
      bovine serum albumins: a spectroscopic approach.
AB  - The interactions of two organoplatinum complexes, [Pt(C^N)Cl(dppa)], 1, and
      [Pt(C^N)Cl(dppm)], 2 (C^N = N(1), C(2')-chelated, deprotonated 2-phenylpyridine,
      dppa = bis(diphenylphosphino)amine, dppm = bis(diphenylphosphino)methane), as
      antitumor agents, with bovine serum albumin (BSA) and human serum albumin (HSA)
      have been studied by fluorescence and UV-vis absorption spectroscopic techniques
      at pH 7.40. The quenching constants and binding parameters (binding constants and
      number of binding sites) were determined by fluorescence quenching method. The
      obtained results revealed that there is a strong binding interaction between the
      ligands and proteins. The calculated thermodynamic parameters (DeltaG, DeltaH,
      and DeltaS) confirmed that the binding reaction is mainly entropy-driven, and
      hydrophobic forces played a major role in the reaction. The displacement
      experiment shows that these Pt complexes can bind to the subdomain IIA (site I)
      of albumin. Moreover, synchronous fluorescence spectroscopy studies revealed some
      changes in the local polarity around the tryptophan residues. Finally, the
      distance, r, between donor (serum albumin) and acceptor (Pt complexes) was
      obtained according to Forster theory of nonradiation energy transfer.

PMID- 22364152
TI  - Clinicopathological study of invasive extramammary Paget's disease: subgroup
      comparison according to invasion depth.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a distinct form of malignant
      skin neoplasm. Invasive EMPD is relatively rare and its detailed
      histopathological features have not been investigated to date. METHODS: Surgical
      specimens were obtained from 51 patients with primary invasive EMPD. Clinical
      data including lymph node status were retrieved from the patients' medical
      records. Cases were divided into subgroups according to invasion depth: dermal
      invasion <= 1 mm (minimal invasion) and dermal invasion > 1 mm in depth.
      Histological patterns (nodular/glandular pattern or micronodular pattern),
      lymphatic/venous invasion, mitosis and lymph node status were compared between
      the two groups. RESULTS: The invasive EMPDs included 26 cases (51.0%) with dermal
      invasion <= 1 mm (minimal invasion) and 25 cases (49.0%) with dermal invasion > 1
      mm in depth. Lymph node metastasis was detected in 2/26 (7.7%) patients with
      minimally invasive EMPD. Nodular/glandular pattern (72.0%), lymphatic/venous
      invasion (52.0%), mitosis (88.0%) and nodal metastasis (88.0%) were all
      significantly more frequent in cases with dermal invasion > 1 mm, compared to
      EMPDs with dermal invasion <= 1 mm (minimal invasion) (P < 0.001). CONCLUSION:
      These results suggest that invasive EMPD can be divided according to invasion
      depth, with a cut-off depth of 1 mm. This might represent the basis for a useful,
      EMPD-specific staging system.

PMID- 22364151
TI  - Oligosaccharide and peptidoglycan of Ganoderma lucidum activate the immune
      response in human mononuclear cells.
AB  - The acid-hydrolyzed fragments of  Ganoderma lucidum  polysaccharides (GLPS)
      obtained by Smith degradation were separated by size-exclusion chromatography
      into two major water-soluble fractions: peptidoglycans (GLPS-SF1) and
      oligosaccharides (GLPS-SF2). Both fractions induced CD69 in human peripheral
      blood mononuclear cells (hPB-MNCs), and they displayed distinct immunomodulating
      properties. GLPS-SF1, with a molecular weight of around 20 kDa, were
      heterogeneous peptidoglycans composed of glucose/mannose (4:1) that exhibited
      biological activities with Th1 cytokines IL-12, IL-2, TNF-alpha, and IFN-gamma in
      hPB-MNCs and stimulated macrophage cytokine expression via Toll-like receptor 4
      (TLR4) signaling. For GLPS-SF2, with a molecular weight of around several
      kilodaltons, its sugar sequence was elucidated by mass spectrometry (MS) and
      nuclear magnetic resonance (NMR) spectroscopy as [-alpha-1,4-Glc-(beta-1,4
      GlcA)(3)-](n). This oligosaccharide displayed specific immune property with low
      monocyte induction, greatly stimulated cell activation and proliferation of NK
      and T cells. This oligosaccharide isolated from  G. lucidum  polysaccharides with
      internal glucuronic acids/glucose repeat unit in a 3:1 ratio may be responsible
      for the active stimulation of NK and T cells.

PMID- 22364153
TI  - A conserved two-component regulatory system, PidS/PidR, globally regulates
      pigmentation and virulence-related phenotypes of Burkholderia glumae.
AB  - Burkholderia glumae is a rice pathogenic bacterium that causes bacterial panicle
      blight. Some strains of this pathogen produce dark brown pigments when grown on
      casamino-acid peptone glucose (CPG) agar medium. A pigment-positive and highly
      virulent strain of B. glumae, 411gr-6, was randomly mutagenized with mini-Tn5gus,
      and the resulting mini-Tn5gus derivatives showing altered pigmentation phenotypes
      were screened on CPG agar plates to identify the genetic elements governing the
      pigmentation of B. glumae. In this study, a novel two-component regulatory system
      (TCRS) composed of the PidS sensor histidine kinase and the PidR response
      regulator was identified as an essential regulatory factor for pigmentation.
      Notably, the PidS/PidR TCRS was also required for the elicitation of the
      hypersensitive response on tobacco leaves, indicating the dependence of the
      hypersensitive response and pathogenicity (Hrp) type III secretion system of B.
      glumae on this regulatory factor. In addition, B. glumae mutants defective in the
      PidS/PidR TCRS showed less production of the phytotoxin, toxoflavin, and less
      virulence on rice panicles and onion bulbs relative to the parental strain, 411gr
      6. The presence of highly homologous PidS and PidR orthologues in other
      Burkholderia species suggests that PidS/PidR-family TCRSs may exert the same or
      similar functions in different Burkholderia species, including both plant and
      animal pathogens.

PMID- 22364154
TI  - Epigenomics and chromatin dynamics.
AB  - A report of the 'Joint Keystone Symposium on Epigenomics and Chromatin Dynamics',
      Keystone, Colorado, 17-22 January 2012.

PMID- 22364156
TI  - Beyond overweight: nutrition as an important lifestyle factor influencing timing
      of puberty.
AB  - Early onset of puberty may confer adverse health consequences. Thus, modifiable
      factors influencing the timing of puberty are of public health interest.
      Childhood overweight as a factor in the earlier onset of menarche has been
      supported by prospective evidence; nonetheless, its overall contribution may have
      been overemphasized, since secular trends toward a younger age at menarche have
      not been a universal finding during the recent obesity epidemic. Current
      observational studies suggest notable associations between dietary intakes and
      pubertal timing beyond contributions to an energy imbalance: children with the
      highest intakes of vegetable protein or animal protein experience pubertal onset
      up to 7 months later or 7 months earlier, respectively. Furthermore, girls with
      high isoflavone intakes may experience the onset of breast development and peak
      height velocity approximately 7-8 months later. These effect sizes are on the
      order of those observed for potentially neuroactive steroid hormones. Thus,
      dietary patterns characterized by higher intakes of vegetable protein and
      isoflavones and lower intakes of animal protein may contribute to a lower risk of
      breast cancer or a lower total mortality.

PMID- 22364155
TI  - Cardiovascular outcomes associated with concomitant use of clopidogrel and proton
      pump inhibitors in patients with acute coronary syndrome in Taiwan.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Conflicting results have been reported
      regarding the increased risk of adverse outcomes in the concomitant use of
      clopidogrel and proton pump inhibitors (PPIs) compared with the use of
      clopidogrel alone. WHAT THIS STUDY ADDS: Our study indicated no statistically
      significant increase in the risk of rehospitalization for acute coronary syndrome
      due to concurrent use of clopidogrel and PPIs in an Asian population with higher
      prevalence of CYP2C19 intermediate and poor metabolizers. Among all PPIs, only
      omeprazole was found to be statistically significantly associated with an
      increased risk of rehospitalization for acute coronary syndrome. AIMS Our study
      aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs)
      with clopidogrel on the cardiovascular outcomes of patients with acute coronary
      syndrome (ACS). Furthermore, we sought to quantify the effects of five individual
      PPIs when used concomitantly with clopidogrel. METHODS: We conducted a
      retrospective cohort study of patients who were newly hospitalized for ACS
      between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National
      Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel
      (n= 37 099) during the follow-up period. A propensity score technique was used to
      establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary
      clinical outcome was rehospitalization for ACS, while secondary outcomes were
      rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with
      stent, PTCA without stent and revascularization (PTCA or coronary artery bypass
      graft surgery) after the discharge date for the index ACS event. RESULTS: The
      adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence
      interval, 0.971-1.139; P= 0.214) in the propensity score matched cohort. Among
      all PPIs, only omeprazole was found to be statistically significantly associated
      with an increased risk of rehospitalization for ACS (adjusted hazard ratio,
      1.226; 95% confidence interval, 1.066-1.410; P= 0.004). Concomitant use of
      esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the
      risk. CONCLUSIONS: Our study indicated no statistically significant increase in
      the risk of rehospitalization for ACS due to concurrent use of clopidogrel and
      PPIs overall. Among individual PPIs, only omeprazole was found to be
      statistically significantly associated with increased risk of rehospitalization
      for ACS.

PMID- 22364157
TI  - Suboptimal magnesium status in the United States: are the health consequences
      underestimated?
AB  - In comparison with calcium, magnesium is an "orphan nutrient" that has been
      studied considerably less heavily. Low magnesium intakes and blood levels have
      been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive
      protein, hypertension, atherosclerotic vascular disease, sudden cardiac death,
      osteoporosis, migraine headache, asthma, and colon cancer. Almost half (48%) of
      the US population consumed less than the required amount of magnesium from food
      in 2005-2006, and the figure was down from 56% in 2001-2002. Surveys conducted
      over 30 years indicate rising calcium-to-magnesium food-intake ratios among
      adults and the elderly in the United States, excluding intake from supplements,
      which favor calcium over magnesium. The prevalence and incidence of type 2
      diabetes in the United States increased sharply between 1994 and 2001 as the
      ratio of calcium-to-magnesium intake from food rose from <3.0 to >3.0. Dietary
      Reference Intakes determined by balance studies may be misleading if subjects
      have chronic latent magnesium deficiency but are assumed to be healthy. Cellular
      magnesium deficit, perhaps involving TRPM6/7 channels, elicits calcium-activated
      inflammatory cascades independent of injury or pathogens. Refining the magnesium
      requirements and understanding how low magnesium status and rising calcium-to
      magnesium ratios influence the incidence of type 2 diabetes, metabolic syndrome,
      osteoporosis, and other inflammation-related disorders are research priorities.

PMID- 22364158
TI  - The nutrient problem.
AB  - Nutrient intake recommendations, unlike hormone replacement standards, are based
      empirically, rather than physiologically, i.e., they lack an a priori normal
      referent. Randomized controlled trials do not provide the needed referent and are
      unlikely to distinguish between fully normal and various suboptimal nutritional
      states. Several alternative approaches, each providing an a priori normal, are
      described and briefly discussed.

PMID- 22364159
TI  - Sulfur amino acid metabolism and requirements.

PMID- 22364160
TI  - Effects of decreased availability of sulfur amino acids in severe childhood
      undernutrition.
AB  - In studies of glutathione (GSH) metabolism in children with severe childhood
      undernutrition (SCU), slower erythrocyte GSH synthesis in children with edema was
      associated with lower concentrations of cysteine, the rate-limiting precursor of
      GSH synthesis. This finding suggested a shortage of cysteine available for GSH
      synthesis in children with edematous SCU. The plasma concentration of methionine,
      the sulfur donor for cysteine synthesis, was also lower in children with
      edematous SCU, suggesting decreased availability of methionine for cysteine
      synthesis. It is also possible that reduced methionine availability will result
      in decreased synthesis of S-adenosylmethionine, which could lead to an overall
      defect in methylation reactions. This review focuses on the relationship between
      cysteine availability and GSH synthesis in children with SCU. It also examines
      whether there is an inadequate supply of cysteine in those with edematous SCU
      and, if so, whether this is due to a shortage of methionine due to a decreased
      release of methionine from protein breakdown. Finally, the review explores
      whether a shortage of methionine results in decreased synthesis of S
      adenosylmethionine, the universal methyl donor.

PMID- 22364161
TI  - Policies to promote healthy eating in Europe: a structured review of policies and
      their effectiveness.
AB  - This review provides a classification of public policies to promote healthier
      eating as well as a structured mapping of existing measures in Europe. Complete
      coverage of alternative policy types was ensured by complementing the review with
      a selection of major interventions from outside Europe. Under the auspices of the
      Seventh Framework Programme's Eatwell Project, funded by the European Commission,
      researchers from five countries reviewed a representative selection of policy
      actions based on scientific papers, policy documents, grey literature, government
      websites, other policy reviews, and interviews with policy-makers. This work
      resulted in a list of 129 policy interventions, 121 of which were in Europe. For
      each type of policy, a critical review of its effectiveness was conducted, based
      on the evidence currently available. The results of this review indicate a need
      exists for a more systematic and accurate evaluation of government-level
      interventions as well as for a stronger focus on actual behavioral change rather
      than changes in attitude or intentions alone. The currently available evidence is
      very heterogeneous across policy types and is often incomplete.

PMID- 22364163
TI  - Phylogeographic reconstruction of HIV type 1B in Montenegro and the Balkan
      region.
AB  - Human immunodeficiency virus (HIV) is one of the most genetically variable human
      viruses as it is characterized by high rates of mutation, viral replication, and
      recombination. Phylodynamics is a powerful means of describing the behavior of an
      infection as a combination of evolutionary and ecological processes. Only a few
      studies of HIV-1 molecular epidemiology have so far been carried out in the
      Balkans. In this study, we used Bayesian methods to reconstruct the
      phylogeography and phylodynamics of HIV-1B in Montenegro and some other Balkan
      countries on the basis of pol gene sequences retrieved from a public database.
      The phylogenetic analysis showed that 43% of the isolates grouped in accordance
      with their geographic area, whereas the majority were interspersed in the tree,
      thus confirming the multiple introductions of HIV-1B in the Balkans. The Bayesian
      phylogeographic analysis suggested that HIV-1B entered the Balkans in the early
      1970s probably through Greece and other Mediterranean tourist/travel destinations
      (such as Slovenia). Other Balkan countries, such as Bulgaria and Serbia, may have
      played an important role in spreading the infection to the entire Eastern
      Mediterranean area, and possibly to Northeast Europe. This suggests that the
      Balkans may have played a role as a "gateway" between Western and Eastern Europe.

PMID- 22364164
TI  - Land and water impacts of oil sands production in Alberta.
AB  - Expansion of oil sands development results not only in the release of greenhouse
      gas emissions, but also impacts land and water resources. Though less discussed
      internationally due to to their inherently local nature, land and water impacts
      can be severe. Research in key areas is needed to manage oil sands operations
      effectively; including improved monitoring of ground and surface water quality.
      The resulting information gap means that such impacts are not well understood.
      Improved analyses of oil sands products are required that compare land and water
      use with other transportation fuel pathways and use a regional perspective so
      local effects can be considered and mitigated.

PMID- 22364166
TI  - If roflumilast inhibits the innate immunity in the stable patient, what about
      infection?

PMID- 22364167
TI  - Dietary moderately oxidized oil activates the Nrf2 signaling pathway in the liver
      of pigs.
AB  - BACKGROUND: Previous studies have shown that administration of oxidized oils
      increases gene expression and activities of various enzymes involved in
      xenobiotic metabolism and stress response in the liver of rats and guinea pigs.
      As these genes are controlled by nuclear factor erythroid-derived 2-like 2
      (Nrf2), we investigated the hypothesis that feeding of oxidized fats causes an
      activation of that transcription factor in the liver which in turn activates the
      expression of antioxidant, cytoprotective and detoxifying genes. METHODS: Twenty
      four crossbred pigs were allocated to two groups of 12 pigs each and fed
      nutritionally adequate diets with either fresh rapeseed oil (fresh fat group) or
      oxidized rapeseed oil prepared by heating at a temperature of 175 degrees C for
      72 h (oxidized fat group). RESULTS: After 29 days of feeding, pigs of the
      oxidized fat group had a markedly increased nuclear concentration of the
      transcription factor Nrf2 and a higher activity of cellular superoxide dismutase
      and T4-UDP glucuronosyltransferase in liver than the fresh fat group (P < 0.05).
      In addition, transcript levels of antioxidant and phase II genes in liver, like
      superoxide dismutase 1, heme oxygenase 1, glutathione peroxidase 1, thioredoxin
      reductase 1, microsomal glutathione-S-transferase 1, UDP glucuronosyltransferase
      1A1 and NAD(P)H:quinone oxidoreductase 1 in the liver were higher in the oxidized
      fat group than in the fresh fat group (P < 0.05). Moreover, pigs of the oxidized
      fat group had an increased hepatic nuclear concentration of the transcription
      factor NF-kappaB which is also an important transcription factor mediating
      cellular stress response. CONCLUSION: The present study shows for the first time
      that administration of an oxidized fat activates the Nrf2 in the liver of pigs
      which likely reflects an adaptive mechanism to prevent cellular oxidative damage.
      Activation of the NF-kappaB pathway might also contribute to this effect of
      oxidized fat.

PMID- 22364165
TI  - The relationship between the MMP system, adrenoceptors and phosphoprotein
      phosphatases.
AB  - The MMPs and their inhibitors [tissue inhibitor of MMPs (TIMPs)] form the
      mainstay of extracellular matrix homeostasis. They are expressed in response to
      numerous stimuli including cytokines and GPCR activation. This review highlights
      the importance of adrenoceptors and phosphoprotein phosphatases (PPP) in
      regulating MMPs in the cardiovascular system, which may help explain some of the
      beneficial effects of targeting the adrenoceptor system in tissue remodelling and
      will establish emerging crosstalk between these three systems. Although alpha-
      and beta-adrenoceptor activation increases MMP but decreases TIMP expression,
      MMPs are implicated in the growth stimulatory effects of adrenoceptor activation
      through transactivation of epidermal growth factor receptor. Furthermore, they
      have recently been found to catalyse the proteolysis of beta-adrenoceptors and
      modulate vascular tone. While the mechanisms underpinning these effects are not
      well defined, reversible protein phosphorylation by kinases and phosphatases may
      be key. In particular, PPP (Ser/Thr phosphatases) are not only critical in
      resensitization and internalization of adrenoceptors but also modulate MMP
      expression. The interrelationship is complex as isoprenaline (ISO) inhibits
      okadaic acid [phosphoprotein phosphatase type 1/phosphoprotein phosphatase type
      2A (PP2A) inhibitor]-mediated MMP expression. While this may be simply due to its
      ability to transiently increase PP2A activity, there is evidence for MMP-9 that
      ISO prevents okadaic acid-mediated expression of MMP-9 through a beta-arrestin,
      NF-kappaB-dependent pathway, which is abolished by knock-down of PP2A. It is
      essential that crosstalk between MMPs, adrenoceptors and PPP are investigated
      further as it will provide important insight into how adrenoceptors modulate
      cardiovascular remodelling, and may identify new targets for pharmacological
      manipulation of the MMP system.

PMID- 22364168
TI  - Social relevance enhances memory for impressions in older adults.
AB  - Previous research has demonstrated that older adults have difficulty retrieving
      contextual material over items alone. Recent research suggests this deficit can
      be reduced by adding emotional context, allowing for the possibility that memory
      for social impressions may show less age-related decline than memory for other
      types of contextual information. Two studies investigated how orienting to social
      or self-relevant aspects of information contributed to the learning and retrieval
      of impressions in young and older adults. Participants encoded impressions of
      others in conditions varying in the use of self-reference (Experiment 1) and
      interpersonal meaningfulness (Experiment 2), and completed memory tasks requiring
      the retrieval of specific traits. For both experiments, age groups remembered
      similar numbers of impressions. In Experiment 1 using more self-relevant encoding
      contexts increased memory for impressions over orienting to stimuli in a non
      social way, regardless of age. In Experiment 2 older adults had enhanced memory
      for impressions presented in an interpersonally meaningful relative to a
      personally irrelevant way, whereas young adults were unaffected by this
      manipulation. The results provide evidence that increasing social relevance
      ameliorates age differences in memory for impressions, and enhances older adults'
      ability to successfully retrieve contextual information.

PMID- 22364170
TI  - Measuring binding of protein to gel-bound ligands using magnetic levitation.
AB  - This paper describes the use of magnetic levitation (MagLev) to measure the
      association of proteins and ligands. The method starts with diamagnetic gel beads
      that are functionalized covalently with small molecules (putative ligands).
      Binding of protein to the ligands within the bead causes a change in the density
      of the bead. When these beads are suspended in a paramagnetic aqueous buffer and
      placed between the poles of two NbFeB magnets with like poles facing, the changes
      in the density of the bead on binding of protein result in changes in the
      levitation height of the bead that can be used to quantify the amount of protein
      bound. This paper uses a reaction-diffusion model to examine the physical
      principles that determine the values of rate and equilibrium constants measured
      by this system, using the well-defined model system of carbonic anhydrase and
      aryl sulfonamides. By tuning the experimental protocol, the method is capable of
      quantifying either the concentration of protein in a solution, or the binding
      affinities of a protein to several resin-bound small molecules simultaneously.
      Since this method requires no electricity and only a single piece of inexpensive
      equipment, it may find use in situations where portability and low cost are
      important, such as in bioanalysis in resource-limited settings, point-of-care
      diagnosis, veterinary medicine, and plant pathology. It still has several
      practical disadvantages. Most notably, the method requires relatively long assay
      times and cannot be applied to large proteins (>70 kDa), including antibodies.
      The design and synthesis of beads with improved characteristics (e.g., larger
      pore size) has the potential to resolve these problems.

PMID- 22364171
TI  - A preliminary retrospective study about the relationship between ductus venosus
      Doppler indices, nuchal translucency (NT) and biochemical markers in the first
      and second trimester screening tests.
AB  - In our study, we tried to assess the relation between ductus venosus Doppler
      indices [pulsatility index (PI), resistance index (RI) and S/D] and first
      trimester screening markers (MoM of serum pregnancy-associated plasma protein A,
      pappalysin 1 (PAPP-A), MoM of serum free beta-human chorionic gonadotrophin (beta
      hCG), and nuchal translucency (NT) and second trimester screening markers (MoM of
      serum alpha-fetoprotein, MoM of serum total beta-hCG and MoM of serum estriol).
      We analyzed the data of 121 singleton pregnancies. Roche cobas e 601ECLIA
      (electrochemiluminescence immunoassay) was used to measure MoM of serum PAPP-A
      and Roche cobas e 602 ECLIA (electrochemiluminescence immunoassay) was used to
      measure MoM of serum free beta-hCG in the first trimester. Beckman Coulter Access
      2 Immunoassay was used to measure MoM of serum alpha-fetoprotein, MoM of serum
      total beta-hCG and MoM of serum estriol in the second trimester. The first author
      performed all ultrasound screenings and ductus venosus Doppler studies. What we
      found new in our study is presented as following; MoM of serum alpha-fetoprotein
      had a negative correlation with RI of ductus venosus Doppler, MoM of serum
      estriol had a negative correlation with RI of ductus venosus Doppler and MoM of
      serum estriol had a negative correlation with S/D of ductus venosus doppler. The
      results of our study suggest that ductus venosus Doppler can be used to increase
      the effectiveness of the second trimester screening test.

PMID- 22364172
TI  - Nanoporous PtCo surface alloy architecture with enhanced properties for methanol
      electrooxidation.
AB  - By selectively dealloying a PtCoAl ternary alloy, a novel nanoporous PtCo (np
      PtCo) alloy with a three-dimensional bicontinuous pore-ligament structure is
      successfully fabricated. X-ray diffraction and electron microscopic
      characterizations demonstrate the single-crystal nature of the alloy ligament
      with a ligament size down to ~3 nm. After a mild electrochemical dealloying
      process, a nanoporous near-surface alloy structure with a Pt-rich surface and a
      PtCo alloy core is obtained. Electrochemical measurements show that the np-PtCo
      surface alloy has greatly enhanced catalytic activity and durability toward
      methanol electrooxidation compared with a state-of-the-art Pt/C catalyst. The
      peak current density of methanol electrooxidation on a np-PtCo surface alloy is
      more than 5 times of that on Pt/C. More importantly, continuous potential cycling
      from 0.6 to 0.9 V (vs RHE) in a 0.5 M H(2)SO(4) aqueous solution demonstrates
      that a np-PtCo surface alloy has excellent structure stability, with more than
      90% of the initial electrochemical active surface area (EASA) retained after 5000
      potential cycles. Under the same conditions, the EASA of Pt/C drops to ~70%. With
      evident advantages of facile preparation as well as enhanced electrocatalytic
      activity and durability, a np-PtCo surface alloy nanomaterial holds great
      potential as an anode catalyst in direct methanol fuel cells.

PMID- 22364173
TI  - Upper rim guanidinocalix[4]arenes as artificial phosphodiesterases.
AB  - Calix[4]arene derivatives, blocked in the cone conformation and functionalized
      with two to four guanidinium units at the upper rim were synthesized and
      investigated as catalysts in the cleavage of the RNA model compound 2
      hydroxypropyl p-nitrophenyl phosphate. When compared with the behavior of a
      monofunctional model compound, the catalytic superiority of the calix[4]arene
      derivatives points to a high level of cooperation between catalytic groups.
      Combination of acidity measurements with the pH dependence of catalytic rates
      unequivocally shows that a necessary requisite for effective catalysis is the
      simultaneous presence, on the same molecular framework, of a neutral guanidine
      acting as a general base and a protonated guanidine acting as an electrophilic
      activator. The additional guanidinium (guanidine) group in the diprotonated
      (monoprotonated) trifunctional calix[4]arene acts as a more or less innocent
      spectator. This is not the case with the tetrasubstituted calix[4]arene, whose
      mono-, di-, and triprotonated forms are slightly less effective than the
      corresponding di- and triguanidinocalix[4]arene derivatives, most likely on
      account of a steric interference with HPNP caused by overcrowding.

PMID- 22364175
TI  - One-pot noninjection synthesis of Cu-doped Zn(x)Cd(1-x)S nanocrystals with
      emission color tunable over entire visible spectrum.
AB  - Unlike Mn doped quantum dots (d-dots), the emission color of Cu dopant in Cu d
      dots is dependent on the nature, size, and composition of host nanocrystals
      (NCs). The tunable Cu dopant emission has been achieved via tuning the particle
      size of host NCs in previous reports. In this paper, for the first time we doped
      Cu impurity in Zn(x)Cd(1-x)S alloyed NCs and tuned the dopant emission in the
      whole visible spectrum via variation of the stoichiometric ratio of Zn/Cd
      precursors in the host Zn(x)Cd(1-x)S alloyed NCs. A facile noninjection and low
      cost approach for the synthesis of Cu:Zn(x)Cd(1-x)S d-dots was reported. The
      optical properties and structure of the obtained Cu:Zn(x)Cd(1-x)S d-dots have
      been characterized by UV-vis spectroscopy, photoluminescence (PL) spectroscopy,
      transmission electron microscopy (TEM), and X-ray diffraction (XRD). The
      influences of various experimental variables, including Zn/Cd ratio, reaction
      temperature, and Cu dopant concentration, on the optical properties of Cu dopant
      emission have been systematically investigated. The as-prepared Cu:Zn(x)Cd(1-x)S
      d-dots did show PL emission but with quite low quantum yield (QY) (typically
      below 6%). With the deposition of ZnS shell around the Cu:Zn(x)Cd(1-x)S core NCs,
      the PL QY increased substantially with a maximum value of 65%. More importantly,
      the high PL QY can be preserved when the initial oil-soluble d-dots were
      transferred into aqueous media via ligand replacement by mercaptoundeconic acid.
      In addition, these d-dots have thermal stability up to 250  degrees C.

PMID- 22364176
TI  - Mixed vitiligo in childhood: a study on 13 Italian patients.

PMID- 22364177
TI  - Defined xenogeneic-free and hypoxic environment provides superior conditions for
      long-term expansion of human adipose-derived stem cells.
AB  - Development and implementation of therapeutic protocols based on stem cells or
      tissue-engineered products relies on methods that enable the production of
      substantial numbers of cells while complying with stringent quality and safety
      demands. In the current study, we aimed to assess the benefits of maintaining
      cultures of adipose-derived stem cells (ASCs) in a defined culture system devoid
      of xenogeneic components (xeno-free) and hypoxia over a 49-day growth period. Our
      data provide evidence that conditions involving StemPro mesenchymal stem cells
      serum-free medium (SFM) Xeno-Free and hypoxia (5% oxygen concentration) in the
      culture atmosphere provide a superior proliferation rate compared to a standard
      growth environment comprised of alpha-modified Eagle medium (A-MEM) supplemented
      with fetal calf serum (FCS) and ambient air (20% oxygen concentration) or that of
      A-MEM supplemented with FCS and hypoxia. Furthermore, a flow cytometric analysis
      and in vitro differentiation assays confirmed the immunophenotype stability and
      maintained multipotency of ASCs when expanded under xeno-free conditions and
      hypoxia. In conclusion, our data demonstrate that growth conditions utilizing a
      xeno-free and hypoxic environment not only provide an improved environment for
      the expansion of ASCs, but also set the stage as a culture system with the
      potential broad spectrum utility for regenerative medicine and tissue engineering
      applications.

PMID- 22364179
TI  - Clinical competence and childhood cancer - a view from primary care.

PMID- 22364178
TI  - Mobile elements in the human genome: implications for disease.
AB  - Perhaps as much as two-thirds of the mammalian genome is composed of mobile
      genetic elements ('jumping genes'), a fraction of which is still active or can be
      reactivated. By their sheer number and mobility, retrotransposons, DNA
      transposons and endogenous retroviruses have shaped our genotype and phenotype
      both on an evolutionary scale and on an individual level. Notably, at least the
      non-long terminal repeat retrotransposons are still able to cause disease by
      insertional mutagenesis, recombination, providing enzymatic activities for other
      mobile DNA, and perhaps by transcriptional overactivation and epigenetic effects.
      Currently, there are nearly 100 examples of known retroelement insertions that
      cause disease. In this review, we highlight those genome-scale technologies that
      have expanded our knowledge of the diseases that these mobile elements can
      elicit, and we discuss the potential impact of these findings for medicine. It is
      now likely that at least some types of cancer and neurological disorders arise as
      a result of retrotransposon mutagenesis.

PMID- 22364180
TI  - Bimodal effect of retinoic acid on melanocyte differentiation identified by time
      dependent analysis.
AB  - Retinoic acid (RA) is considered to control melanocytes; however, its precise
      mechanism remains unclear because of a bimodal effect, which promotes or inhibits
      melanin synthesis depending on the cell type, culture condition of melanocytes
      and skin conditions. In this study, we examined the effects of RA throughout each
      stage of differentiation of melanocytes using a mouse embryonic stem cell culture
      system to induce melanocytes. The results showed that RA has significantly
      different effects depending on the stage of differentiation of melanocytes. More
      specifically, RA promoted differentiation in earlier stages, wherein embryonic
      stem cells became melanoblasts via neural crest cells, and inhibited
      differentiation in later stages, wherein melanoblasts became melanocytes. It was
      revealed for the first time that melanocytes show markedly different reactions to
      RA depending on the stage of differentiation.

PMID- 22364181
TI  - Identification of simultaneous U(VI) sorption complexes and U(IV)
      nanoprecipitates on the magnetite (111) surface.
AB  - Sequestration of uranium (U) by magnetite is a potentially important sink for U
      in natural and contaminated environments. However, molecular-scale controls that
      favor U(VI) uptake including both adsorption of U(VI) and reduction to U(IV) by
      magnetite remain poorly understood, in particular, the role of U(VI)-CO(3)-Ca
      complexes in inhibiting U(VI) reduction. To investigate U uptake pathways on
      magnetite as a function of U(VI) aqueous speciation, we performed batch sorption
      experiments on (111) surfaces of natural single crystals under a range of
      solution conditions (pH 5 and 10; 0.1 mM U(VI); 1 mM NaNO(3); and with or without
      0.5 mM CO(3) and 0.1 mM Ca) and characterized surface-associated U using grazing
      incidence extended X-ray absorption fine structure spectroscopy (GI-EXAFS),
      grazing incidence X-ray diffraction (GI-XRD), and scanning electron microscopy
      (SEM). In the absence of both carbonate ([CO(3)](T), denoted here as CO(3)) and
      calcium (Ca), or in the presence of CO(3) only, coexisting adsorption of U(VI)
      surface species and reduction to U(IV) occurs at both pH 5 and 10. In the
      presence of both Ca and CO(3), only U(VI) adsorption (VI) occurs. When U
      reduction occurs, nanoparticulate UO(2) forms only within and adjacent to surface
      microtopographic features such as crystal boundaries and cracks. This result
      suggests that U reduction is limited to defect-rich surface regions. Further, at
      both pH 5 and 10 in the presence of both CO(3) and Ca, U(VI)-CO(3)-Ca ternary
      surface species develop and U reduction is inhibited. These findings extend the
      range of conditions under which U(VI)-CO(3)-Ca complexes inhibit U reduction.

PMID- 22364182
TI  - Valvular heart disease in a patient taking 3,4-methylenedioxymethamphetamine
      (MDMA, 'Ecstasy').

PMID- 22364183
TI  - Thermal stability and surface passivation of Ge nanowires coated by epitaxial
      SiGe shells.
AB  - Epitaxial growth of a highly strained, coherent SiGe alloy shell around a Ge
      nanowire core is investigated as a method to achieve surface passivation and
      carrier confinement, important in realizing nanowire devices. The high
      photoluminescence intensity observed from the core-shell nanowires with spectral
      features similar to that of bulk Ge indicates effective surface passivation.
      Thermal stability of these core-shell heterostructures has been systematically
      investigated, with a method demonstrated to avoid misfit strain relaxation during
      postgrowth annealing.

PMID- 22364184
TI  - Synergistic effect of cyanidin and PPAR agonist against nonalcoholic
      steatohepatitis-mediated oxidative stress-induced cytotoxicity through MAPK and
      Nrf2 transduction pathways.
AB  - Nonalcoholic steatohepatitis (NASH) is caused by an elevation in oxidative
      stress, which might further lead to hepatic fibrogenesis. Importantly, both
      peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2
      related factor 2 (Nrf2) play roles in modulating oxidative stress-mediated
      hepatic dysfunction. The objective of this study was to investigate the
      mechanisms of the multifunctional effects of cyanidin on regulating antioxidant
      enzymes and oxidative stress-induced hepatotoxicity. The data indicated that
      cyanidin-mediated antioxidant enzyme expression involved the extracellular signal
      regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways and Nrf2
      activation. Furthermore, the synergistic effect of cyanidin and the PPAR agonist,
      troglitazone, on Nrf2-PPAR activation, was also observed. Besides, treatment of
      cyanidin and troglitazone abolished H2O2-induced downregulation of genes involved
      in lipid metabolism. In addition, H2O2-mediated cytotoxicity, which was caused by
      inducing ROS formation and apoptotic cell death, was also ameliorated upon
      cyanidin and troglitazone stimulation. In conclusion, mitogen-activated protein
      kinases (MAPKs) and the transcription factor Nrf2 played regulatory roles in
      cyanidin-mediated antioxidant enzyme activation. Furthermore, the combination of
      cyanidin and troglitazone activated PPARgamma-Nrf2 and improved H2O2-mediated
      perturbation of genes involved in lipid metabolism. These data suggested that
      cyanidin and PPAR agonists might have synergistic benefits against metabolic
      dysfunction-related oxidative damage.

PMID- 22364186
TI  - Dimensional reduction of a layered metal chalcogenide into a 1D near-IR direct
      band gap semiconductor.
AB  - Reducing the dimensionality of inorganic lattices allows for the creation of new
      materials that have unique optoelectronic properties. We demonstrate that a
      layered metal chalcogenide lattice, TiS(2), can form a dimensionally reduced
      crystalline one-dimensional hybrid organic/inorganic TiS(2)(ethylenediamine)
      framework when synthesized from molecular precursors in solution. This solid has
      strong absorption above 1.70 eV and pronounced emission in the near-IR regime.
      The energy dependence of the absorption, the near-IR photoluminescence, and
      electronic band structure calculations confirm that TiS(2)(ethylenediamine) has a
      direct band gap.

PMID- 22364185
TI  - Recombination between variants from genital tract and plasma: evolution of
      multidrug-resistant HIV type 1.
AB  - Multidrug-resistant (MDR) HIV-1 presents a challenge to the efficacy of
      antiretroviral therapy (ART). To examine mechanisms leading to MDR variants in
      infected individuals, we studied recombination between single viral genomes from
      the genital tract and plasma of a woman initiating ART. We determined HIV-1 RNA
      sequences and drug resistance profiles of 159 unique viral variants obtained
      before ART and semiannually for 4 years thereafter. Soon after initiating
      zidovudine, lamivudine, and nevirapine, resistant variants and intrapatient HIV-1
      recombinants were detected in both compartments; the recombinants had inherited
      genetic material from both genital and plasma-derived viruses. Twenty-three
      unique recombinants were documented during 4 years of therapy, comprising ~22% of
      variants. Most recombinant genomes displayed similar breakpoints and clustered
      phylogenetically, suggesting evolution from common ancestors. Longitudinal
      analysis demonstrated that MDR recombinants were common and persistent,
      demonstrating that recombination, in addition to point mutation, can contribute
      to the evolution of MDR HIV-1 in viremic individuals.

PMID- 22364187
TI  - Identification of putative biomarkers for the serodiagnosis of drug-resistant
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Early diagnosis and treatment of Mycobacterium tuberculosis infection
      can prevent most deaths resulting from this pathogen; however, multidrug
      resistant strains present serious threats to global tuberculosis control and
      prevention efforts. In this study, we identified antigens that could be used for
      the serodiagnosis of drug-resistant M. tuberculosis strains, using a proteomics
      based analysis. RESULTS: Serum from patients infected with drug-resistant or drug
      susceptible M. tuberculosis strains and healthy controls was subjected to two
      dimensional gel electrophoresis using a western blot approach. This procedure
      identified nine immunoreactive proteins, which were subjected to MALDI-TOF-MS
      analysis. Six recombinant proteins, namely rRv2031c, rRv0444c, rRv2145c, rRv3692,
      rRv0859c, and rRv3040, were expressed and used to determine the immuno-reactivity
      of 100 serum samples. Antibody reactivity against rRv2031c, rRv3692, and rRv0444c
      was consistently observed. Among them, the best sensitivity and specificity of
      rRv3692 were 37% and 95% respectively. Furthermore, when rRv2031c and rRv3692 or
      rRv2031c, rRv3692, and rRv0444c were combined in 2:1 or equal amounts, the assay
      sensitivity and specificity were improved to 56.7% and 100% respectively.
      CONCLUSIONS: These results suggest that Rv2031c, Rv3692, and Rv0444c are possible
      candidate biomarkers for effective use in the serodiagnosis of drug-resistant
      tuberculosis infections, and a combined formula of these antigens should be
      considered when designing a subunit assay kit.

PMID- 22364188
TI  - Immunoproteomic identification of 11 novel immunoreactive proteins of Riemerella
      anatipestifer serotype 2.
AB  - Riemerella anatipestifer (RA) is one of the most important bacterial pathogens of
      ducks and other avian species worldwide. Twenty-one serotypes of RA have been
      identified, with RA serotype two (RA2) being reported as one of the most
      predominant serotypes underlying infections in China. Current approaches to the
      control of RA are hindered by the absence of effective vaccines, particularly
      those that exhibit cross-protection between different serotypes. In this study, a
      combination of two-dimensional electrophoresis, Western blot analysis and mass
      spectrometry were used to identify the antigenic proteins of RA2. A total of 16
      immunoreactive proteins, representing 12 distinct proteins, were identified.
      These included OmpA, a known immunogenic protein of RA, as well as novel
      immunogens. PCR analysis also indicated that genes corresponding to each of the
      12 distinct proteins were conserved among different RA serotypes. Eleven genes
      encoding these proteins were cloned and expressed in Escherichia coli BL21 (DE3).
      Eight of the 11 expressed proteins were able to react with hyperimmune rabbit
      serum against RAf153. One of these, recombinant elongation factor G, responded to
      RA2 sera but not RA1, whereas recombinant OmpA responded to both RA1 and RA2
      sera. These data form a basis for the development of vaccine for both homologous
      and heterogeneous RA serotypes in addition to the production of target antigens
      for the development of diagnostic antibodies with the potential to distinguish
      between RA serotypes.

PMID- 22364189
TI  - "All of those things we don't eat": a culture-centered approach to dietary health
      meanings for Asian Indians living in the United States.
AB  - This article applies a culture-centered approach to analyze the dietary health
      meanings for Asian Indians living in the United States. The data were collected
      as part of a health promotion program evaluation designed to help Asian Indians
      reduce their risk of chronic disease. Community members who used two aspects of
      the program participated in two focus groups to learn about their health care
      experiences and to engage them in dialogue about how culture impacts their
      overall health. Using constructionist grounded theory, we demonstrate that one
      aspect of culture, the discourses around routine dietary choice, is an important,
      but underrecognized, aspect of culture that influences community members'
      experiences with health care. We theorize community members' dietary health
      meanings operate discursively through a dialectic tension between homogeneity and
      heterogeneity, situated amid culture, structure, and agency. Participants enacted
      discursive homogeneity when they affirmed dietary health meanings around diet as
      an important means through which members of the community maintain a sense of
      continuity of their identity while differentiating them from others. Participants
      enacted discursive heterogeneity when they voiced dietary health meanings that
      differentiated community members from one another due to unique life-course
      trajectories and other membership affiliations. Through this dialectic, community
      members manage unique Asian Indian identities and create meanings of health and
      illness in and through their discourses around routine dietary choice. Through
      making these discursive health meanings audible, we foreground how community
      members' agency is discursively enacted and to make understandable how discourses
      of dietary practice influence the therapeutic alliance between primary care
      providers and members of a minority community.

PMID- 22364190
TI  - A translational view of biomarkers in preterm labor.
AB  - Preterm labor and birth continue to pose a significant challenge to physicians in
      the obstetrics and neonatal fields. Until specific and effective therapeutic
      treatments are developed to prevent preterm labor, the best means of reducing
      preterm birth rate is early detection and diagnosis. However, current approaches
      to predict preterm labor have had variable success in the clinical setting. In
      this review, we discuss several limitations of using biomarkers from biological
      samples to predict preterm labor. In addition, we propose strategies for
      improving our ability to predict preterm labor, as well as directing therapies
      that are best suited to the underlying cause of preterm labor.

PMID- 22364191
TI  - Validation of an analytical method for the determination of cadmium (Cd) in fish
      by atomic absorption spectrometry with electrothermal atomisation.
AB  - The validation of an analytical method was carried out for the determination of
      cadmium (Cd) in fish. The method was based on sample digestion in a microwave
      oven and subsequent reading using an atomic absorption spectrometer with a
      graphite furnace. The factorial design of experiments was applied to assess
      method ruggedness using the methodology of Box et al. [Box GEP, Hunter WG, Hunter
      JS. 1978. Statistics for experiments: an introduction to design, data analysis
      and model building. New York (NY): Wiley], studying the influence of sample mass,
      volume and concentration of acid used for sample digestion and the volume of
      modifier used. To study the possible matrix effect in the determination of Cd,
      the standard addition method was also performed. The results were treated using
      the OLS method. For the normality test a homoskedastic distribution was observed
      for the developed method and the results were adjusted to the statistical model
      proposed. F-tests and Student's t-tests indicated that there was no matrix effect
      on the calibration curve between the concentration range 1.0-10.0 ug Cd l(-1).
      Parameters such as selectivity, precision, decision limit, detection capability
      and limit of quantification were established by the method of standard addition
      to blank samples. The limit of quantification was 6.8 ug kg(-1). Accuracy, which
      was evaluated by using a certified reference material, was 107.0%. The recovery
      of the spiked analyte was 93.69% for the concentration of 50 ug kg(-1). Precision
      was defined by the coefficient of variation observed (Horrat value), estimated in
      terms of repeatability and reproducibility, and the values were below the limit,
      which is 2.0. The validation procedure confirmed the suitability of the method.

PMID- 22364192
TI  - Nursing students' knowledge and beliefs about care of older adults in a shifting
      context of nursing education.
AB  - AIM:   To a report a study of improvements in students' knowledge and beliefs
      about nursing care of older adults following completion of an introductory course
      with integrated adult/older adult content. Background.  Nursing schools are under
      pressure to provide accelerated programmes to meet growing workforce demands and
      provide students with the knowledge they require to care for an ageing
      population. Thus, stand-alone courses in gerontological nursing are being
      eliminated and integrated with general adult content. The effect of this approach
      remains poorly understood. DESIGN:   A one-group pretest-post-test design was
      used. METHODS:   Data were collected between September-December 2010. Students
      completed the Palmore Facts on Aging Quiz, the Perceptions of Caring for Older
      People Scale, and open-ended questions about their experiences before and after
      completing a course with integrated adult/older content. RESULTS:   Students'
      knowledge and beliefs about nursing care of older adults demonstrated an
      important improvement following completion of the course. Qualitative findings
      reflected three themes: relating to older people; neglect by the system; having
      time to learn. CONCLUSIONS:   Findings from this study suggest that even when
      integrated with general adult content, students' knowledge and beliefs about
      older adult care can be positively influenced. Furthermore research is needed to
      examine long-term integration of students' learning about older adult care.
      Nursing faculty with expertise in nursing care of older adults must develop
      resources and supports for their colleagues to build capacity among nurse
      educators and integrate older adult content throughout nursing programmes to
      enhance nursing practice with an ageing population.

PMID- 22364193
TI  - PTPN22 splice forms: a new role in rheumatoid arthritis.
AB  - Genetic variation in the protein tyrosine phosphatase non-receptor type gene 22
      (PTPN22, encoding lymphoid tyrosine phosphatase, LYP) influences the risk of
      developing multiple autoimmune diseases, but the underlying mechanisms are not
      completely understood. In a recent study published in Genome Medicine, Ronninger
      et al. showed that there are differences in the expression of PTPN22 isoforms
      between peripheral blood mononuclear cells from rheumatoid arthritis patients and
      those of healthy controls. This study provides new insights into the role of
      PTPN22 in autoimmune diseases.

PMID- 22364194
TI  - Molecular dynamics simulation of secondary sorption behavior of montmorillonite
      modified by single chain quaternary ammonium cations.
AB  - Organoclays synthesized from single chain quaternary ammonium cations (QAC)
      ((CH(3))(3)NR(+)) exhibit different mechanisms for the sorption of nonpolar
      organic compounds as the length of the carbon chain is increased. The interaction
      between a nonpolar sorbate and an organoclay intercalated with small QACs has
      been demonstrated to be surface adsorption, while partitioning is the dominant
      mechanism in clays intercalated with long chain surfactants. This study presents
      the results of a molecular dynamics (MD) simulation performed to examine the
      sorption mechanisms of benzene in the interlayer of three organoclays with chain
      lengths ranging from 1 to 16 carbons: tetramethylammonium (TMA) clay;
      decyltrimethylammonium (DTMA) clay; and hexadecyltrimethylammonium (HDTMA) clay.
      The basis of the overall simulation was a combined force field of ClayFF and
      CVFF. In the simulations, organic cations were intercalated and benzene molecules
      were introduced to the interlayer, followed by whole system NPT and NVT time
      integration. Trajectories of all the species were recorded after the system
      reached equilibrium and subsequently analyzed. Simulation results confirmed that
      the arrangement of the surfactants controlled the sorption mechanism of
      organoclays. Benzene molecules were observed to interact directly with the clay
      surface in the presence of TMA cations, but tended to interact with the aliphatic
      chain of the HDTMA cation in the interlayer. The simulation provided insight into
      the nature of the adsorption/partitioning mechanisms in organoclays, and
      explained experimental observations of decreased versus increased uptake
      capacities as a function of increasing total organic carbon (TOC) for TMA clay
      and HDTMA clay, respectively. The transition of sorption mechanisms was also
      quantified with simulation of DTMA clay, with a chain length between that of TMA
      and HDTMA. Furthermore, this study suggested that at the molecular level, the
      controlling factor for the ultimate sorption capacity is available surface sites
      in the case of TMA clay, and density of aliphatic chains within the interlayer
      space for HDTMA clay.

PMID- 22364195
TI  - Memory conformity affects inaccurate memories more than accurate memories.
AB  - After controlling for initial confidence, inaccurate memories were shown to be
      more easily distorted than accurate memories. In two experiments groups of
      participants viewed 50 stimuli and were then presented with these stimuli plus 50
      fillers. During this test phase participants reported their confidence that each
      stimulus was originally shown. This was followed by computer-generated responses
      from a bogus participant. After being exposed to this response participants again
      rated the confidence of their memory. The computer-generated responses
      systematically distorted participants' responses. Memory distortion depended on
      initial memory confidence, with uncertain memories being more malleable than
      confident memories. This effect was moderated by whether the participant's memory
      was initially accurate or inaccurate. Inaccurate memories were more malleable
      than accurate memories. The data were consistent with a model describing two
      types of memory (i.e., recollective and non-recollective memories), which differ
      in how susceptible these memories are to memory distortion.

PMID- 22364196
TI  - Synthesis, structural, and photoluminescence studies of
      Gd(terpy)(H2O)(NO3)2M(CN)2 (M = Au, Ag) complexes: multiple emissions from intra-
      and intermolecular excimers and exciplexes.
AB  - The highly luminescent bimetallic cyanide materials,
      Gd(terpy)(H(2)O)(NO(3))(2)M(CN)(2) (M = Au, Ag; GdAu and GdAg, respectively) are
      quick and easy to synthesize under ambient conditions. A characteristic feature
      exhibited by both solid-state compounds is an intense red emission when excited
      with UV light. Additionally, GdAu exhibits a broad-band green emission upon
      excitation in the near UV region. A combination of structural and spectroscopic
      results for the compounds helps explain the underlying conditions responsible for
      their unique properties. Single-crystal X-ray diffraction experiments expose
      their structural features, including the fact that they are isostructural.
      Crystallographic data for the representative GdAu compound (Mo K(alpha), lambda =
      0.71073 A, T = 290 K): triclinic, space group P 1, a = 7.5707(3) A, b =
      10.0671(4) A, c = 15.1260(4) A, alpha = 74.923(3) degrees , beta = 78.151(3)
      degrees , gamma = 88.401(3) degrees , V = 1089.04(7) A(3), and Z = 2. Although
      the compounds crystallize as dimers containing M...M distances smaller than the
      sum of their van der Waals radii, the Au...Au (3.5054(4) A) and/or the Ag...Ag
      (3.6553(5) A) interactions are relatively weak and are not responsible for the
      low energy red emission. Rather, the green emission in GdAu presumably originates
      from the [Au(CN)(2)(-)](2) dimeric excimer, while the [Ag(CN)(2)(-)](2) dimers in
      GdAg do not display visible emission at either 290 or 77 K. The unusual red
      emission exhibited by both compounds likely originates from the formation of an
      excited state exciplex that involves intermolecular pi-stacking of 2,2':6',2"
      terpyridine ligands. The room-temperature and low-temperature steady-state
      photoluminescent properties, along with detailed time-dependent, lifetime, and
      quantum yield spectroscopic data provide evidence regarding the sources of the
      multiple visible emissions exhibited by these complexes.

PMID- 22364197
TI  - Fractures in a tertiary Neonatal Intensive Care Unit in Wales.
AB  - AIM: To explore associations with fractures reported in a tertiary neonatal
      intensive care unit (NICU). METHOD: Babies admitted to NICU from 1998 to 2007 in
      Cardiff, UK, with fractures during admission were identified. Clinical
      information was extracted from inpatient records. Results were reported as median
      (ranges). RESULTS: Seventy-one fractures were recorded in 27 (boys = 16) infants
      with a gestational age of 28 (23.6-40.4) weeks and birthweight of 920 g (485
      4875). Fractures were recognized at 57 (1-128) days of age. Neonates with
      fractures without clear aetiologies (n = 17) were more preterm (p < 0.001), were
      born lighter (p < 0.001), required multiple medical interventions, were more
      commonly osteopenic (p < 0.001), had fractures detected later (p < 0.001) and had
      more posterior rib fractures (p = 0.009). Rib fractures were detected later than
      other sites (p = 0.002). Associations with rib fractures included osteopenia (p =
      0.04), longer oxygen therapy (p = 0.018), length on total parental nutrition (p =
      0.03), later achievement of full enteral feeds (p = 0.038), sepsis (p = 0.038)
      and surgical procedures (p = 0.004). Posterior rib fractures were more common in
      babies born more preterm (25.1 vs. 29.4 weeks, p = 0.003) and requiring diuretics
      (p = 0.027). CONCLUSION: Fractures in premature infants are associated with a
      variety of predisposing factors. Clinicians evaluating the cause of rib and
      multiple fractures in preterm neonates shortly after discharge need to take these
      factors into consideration.

PMID- 22364198
TI  - Influence of geometry, porosity, and surface characteristics of silica
      nanoparticles on acute toxicity: their vasculature effect and tolerance
      threshold.
AB  - Silica nanoparticles (SiO(2)) are widely used in biomedical applications such as
      drug delivery, cell tracking, and gene transfection. The capability to control
      the geometry, porosity, and surface characteristics of SiO(2) further provides
      new opportunities for their applications in nanomedicine. Concerns however remain
      about the potential toxic effects of SiO(2) upon exposure to biological systems.
      In the present study, the acute toxicity of SiO(2) of systematically varied
      geometry, porosity, and surface characteristics was evaluated in immune-competent
      mice when administered intravenously. Results suggest that in vivo toxicity of
      SiO(2) was mainly influenced by nanoparticle porosity and surface
      characteristics. The maximum tolerated dose (MTD) increased in the following
      order: mesoporous SiO(2) (aspect ratio 1, 2, 8) at 30-65 mg/kg < amine-modified
      mesoporous SiO(2) (aspect ratio 1, 2, 8) at 100-150 mg/kg < unmodified or amine
      modified nonporous SiO(2) at 450 mg/kg. The adverse reactions above MTDs were
      primarily caused by the mechanical obstruction of SiO(2) in the vasculature that
      led to congestion in multiple vital organs and subsequent organ failure. It was
      revealed that hydrodynamic sizes of SiO(2) post-protein exposure had an important
      implication in relating SiO(2) physicochemical properties with their vasculature
      impact and resultant tolerance threshold, as the larger the hydrodynamic size in
      the presence of serum protein, the lower the MTD. This study sheds light on the
      rational design of SiO(2) to minimize in vivo toxicity and provides a critical
      guideline in selecting SiO(2) as the appropriate system for nanomedicine
      applications.

PMID- 22364199
TI  - Glucocorticoid receptors participate in the opiate withdrawal-induced stimulation
      of rats NTS noradrenergic activity and in the somatic signs of morphine
      withdrawal.
AB  - BACKGROUND AND PURPOSE: Recent evidence suggests that glucocorticoid receptor
      (GR) is a major molecular substrate of addictive properties of drugs of abuse.
      Hence, we performed a series of experiments to further characterize the role of
      GR signalling in opiate withdrawal-induced physical signs of dependence, enhanced
      noradrenaline (NA) turnover in the hypothalamic paraventricular nucleus (PVN) and
      tyrosine hydroxylase (TH) phosphorylation (activation) as well as GR expression
      in the nucleus of the solitary tract noradrenergic cell group (NTS-A2).
      EXPERIMENTAL APPROACH: The role of GR signalling was assessed by i.p.
      pretreatment of the selective GR antagonist, mifepristone. Rats were implanted
      with two morphine (or placebo) pellets. Six days later, rats were pretreated with
      mifepristone or vehicle 30 min before naloxone and physical signs of abstinence,
      NA turnover, TH activation, GR expression and the hypothalamus-pituitary
      adrenocortical axis activity were measured using HPLC, immunoblotting and RIA.
      KEY RESULTS: Mifepristone alleviated the somatic signs of naloxone-induced opiate
      withdrawal. Mifepristone attenuated the increase in the NA metabolite, 3-methoxy
      4-hydroxyphenylethylen glycol (MHPG), in the PVN, and the enhanced NA turnover
      observed in morphine-withdrawn rats. Mifepristone antagonized the TH
      phosphorylation at Ser31 and the expression of c-Fos expression induced by
      morphine withdrawal. Finally, naloxone-precipitated morphine withdrawal induced
      up-regulation of GR in the NTS. CONCLUSIONS AND IMPLICATIONS: These results
      suggest that the physical signs of opiate withdrawal, TH activation and
      stimulation of noradrenergic pathways innervating the PVN are modulated by GR
      signalling. Overall, the present data suggest that drugs targeting the GR may
      ameliorate stress and aversive effects associated with opiate withdrawal.

PMID- 22364200
TI  - Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and
      HBD3 ligands.
AB  - Binding of melanocortin peptide agonists to the melanocortin-1 receptor of
      melanocytes results in eumelanin production, whereas binding of the agouti
      signalling protein inverse agonist results in pheomelanin synthesis. Recently, a
      novel melanocortin-1 receptor ligand was reported. A beta-defensin gene mutation
      was found to be responsible for black coat colour in domestic dogs. Notably, the
      human equivalent, beta-defensin 3, was found to bind with high affinity to the
      melanocortin-1 receptor; however, the action of beta-defensin as an agonist or
      antagonist was unknown. Here, we use in vitro assays to show that beta-defensin 3
      is able to act as a weak partial agonist for cAMP signalling in human embryonic
      kidney (HEK) cells expressing human melanocortin-1 receptor. beta-defensin 3 is
      also able to activate MAPK signalling in HEK cells stably expressing either wild
      type or variant melanocortin-1 receptors. We suggest that beta-defensin 3 may be
      a novel melanocortin-1 receptor agonist involved in regulating melanocyte
      responses in humans.

PMID- 22364201
TI  - Clinical epidemiological analysis of 173 supernumerary molars.
AB  - OBJECTIVES: To determine the prevalence of supernumerary molars in a sector of
      the population of Madrid, as well as the possible complications associated with
      the presence of hypergenetic molars. MATERIALS AND METHODS: A retrospective,
      descriptive study was carried out, which included a data assessment of all
      patients (13557) seeking dental care at a hospital's department of oral surgery
      across 4 years. The proposed methodology consisted of preparing a medical record
      in order to obtain data on the medical record number, age and sex of the patient,
      radiological findings such as location and type of supernumerary molar,
      retained/erupted molar, related accidents and tooth morphology. RESULTS:
      Supernumerary molars were found to be present in 130 patients, representing a
      prevalence of 0.96% of the total population studied. These patients had a total
      of 173 hypergenetic molars, consisting of 137 distomolars and 36 paramolars
      Mechanical-obstructive pathology was associated with 28.9%, whereas enlargement
      of the follicular sack bigger than 3 mm was present in 16.2% of the sample.
      CONCLUSION: Supernumerary molars are usually diagnosed as a coincidental
      radiological finding without any associated pathology. However a higher
      percentage of comorbidity was found than initially expected.

PMID- 22364202
TI  - Enantioselective organocatalytic intramolecular Diels-Alder reactions: a
      computational study.
AB  - The diastereo- and enantioselectivity obtained experimentally by Christmann in
      the amine-catalyzed intramolecular Diels-Alder reaction of alpha,beta-unsaturated
      carbonylic compounds were fully rationalized using density functional theory
      methods at the PBE1PBE/6-311+G** level. A polarizable continuum model was used to
      describe solvent effects. The selectivity is induced in the cyclization step, and
      while the enantioselectivity results from the syn/anti orientation around the C-N
      enamine bond, the diastereoselectivity mainly results from the syn/anti
      configuration of the substituents in the forming cyclopentane ring. The
      remarkable reaction rate experimentally observed when an external protic acid is
      used is attributed to the strong decrease in the activation energy of all steps
      needed for the enamine formation, while the external acid marginally influences
      the cyclization step. When hydrogen-bond-donor catalysts are used, the formation
      of one hydrogen bond in the cyclization step inverts the configuration and
      reduces the selectivity. The different behavior between dialdehydes and
      ketoaldehydes is suggested to be resulting from different reaction rates in the
      catalyst elimination step.

PMID- 22364203
TI  - Elevated gene expression in chalcone synthase enzyme suggests an increased
      production of flavonoids in skin and synchronized red cell cultures of North
      American native grape berries.
AB  - Anthocyanins are antioxidants and are among the natural products synthesized via
      the flavonoid biosynthesis pathway. Anthocyanins have been recommended for
      dietary intake in the prevention of cardiovascular diseases, cancer, and age
      related conditions such as Alzheimer's disease or dementia. With an increasingly
      aging population in many parts of the world, strategies for the commercial
      production of in vitro synchronized red cell cultures as natural antioxidants
      will be a significant contribution to human medicine. Red pigmented fruits such
      as grapes (Vitis sp.) are a major source of bioavailable anthocyanins and other
      polyphenols. Since the level of antioxidants varies among cultivars, this study
      is the first one that phytochemically and genetically characterizes native grape
      cultivars of North America to determine the optimal cultivar and berry cells for
      the production of anthocyanins as antioxidants. Using real-time PCR and
      bioinformatics approaches, we tested for the transcript expression of the
      chalcone synthase (CHS) gene, an enzyme involved in the flavonoid and anthocyanin
      biosynthesis pathway, in different parts of physiologically mature grape berries
      and in vitro synchronized red cells. A low level of expression was recorded in
      berry flesh, compared with an elevated expression in berry skins and in vitro
      synchronized red cells, suggesting increased production of flavonoids in skin and
      cell cultures. This preliminary study demonstrates the potential of functional
      genomics in natural products research as well as in systematic studies of North
      American native grapes, specifically in muscadine (Vitis rotundifolia).

PMID- 22364206
TI  - A survey of Sub-Saharan African medical schools.
AB  - BACKGROUND: Sub-Saharan Africa suffers a disproportionate share of the world's
      burden of disease while having some of the world's greatest health care workforce
      shortages. Doctors are an important component of any high functioning health care
      system. However, efforts to strengthen the doctor workforce in the region have
      been limited by a small number of medical schools with limited enrolments,
      international migration of graduates, poor geographic distribution of doctors,
      and insufficient data on medical schools. The goal of the Sub-Saharan African
      Medical Schools Study (SAMSS) is to increase the level of understanding and
      expand the baseline data on medical schools in the region. METHODS: The SAMSS
      survey is a descriptive survey study of Sub-Saharan African medical schools. The
      survey instrument included quantitative and qualitative questions focused on
      institutional characteristics, student profiles, curricula, post-graduate medical
      education, teaching staff, resources, barriers to capacity expansion, educational
      innovations, and external relationships with government and non-governmental
      organizations. Surveys were sent via e-mail to medical school deans or officials
      designated by the dean. Analysis is both descriptive and multivariable. RESULTS:
      Surveys were distributed to 146 medical schools in 40 of 48 Sub-Saharan African
      countries. One hundred and five responses were received (72% response rate). An
      additional 23 schools were identified after the close of the survey period. Fifty
      eight respondents have been founded since 1990, including 22 private schools.
      Enrolments for medical schools range from 2 to 1800 and graduates range from 4 to
      384. Seventy-three percent of respondents (n = 64) increased first year
      enrolments in the past five years. On average, 26% of respondents' graduates were
      reported to migrate out of the country within five years of graduation (n = 68).
      The most significant reported barriers to increasing the number of graduates, and
      improving quality, related to infrastructure and faculty limitations,
      respectively. Significant correlations were seen between schools implementing
      increased faculty salaries and bonuses, and lower percentage loss of faculty over
      the previous five years (P = 0.018); strengthened institutional research tools (P
      = 0.00015) and funded faculty research time (P = 0.045) and greater faculty
      involvement in research; and country compulsory service requirements (P = 0.039),
      a moderate number (1-5) of post-graduate medical education programs (P = 0.016)
      and francophone schools (P = 0.016) and greater rural general practice after
      graduation. CONCLUSIONS: The results of the SAMSS survey increases the level of
      data and understanding of medical schools in Sub-Saharan Africa. This data serves
      as a baseline for future research, policies and investment in the health care
      workforce in the region which will be necessary for improving health.

PMID- 22364207
TI  - Kinetics and morphology of polymicrobial biofilm formation on polypropylene mesh.
AB  - We examined the ability of three clinical bacterial isolates to form mixed
      biofilms on surgical polypropylene mesh (PPM) in vitro. The three strains-
      Staphylococcus aureus, Enterococcus faecalis, and Enterobacter cloacae--were
      isolated from a patient with an infected PPM. Staphylococcus aureus and E.
      faecalis (alone and in combination) were inoculated into culture containing
      squares of PPM and allowed to attach and propagate into mature biofilms.
      Enterococcus faecalis initially attached to the mesh in greater numbers; however,
      7 days postinoculation, there were more S. aureus cells attached, indicating that
      in vitro S. aureus is the out-competing species. All three isolates were then co
      cultured to form mature biofilms on mesh, and the biofilms were examined by
      confocal microscopy using both Live/Dead staining and fluorescent in situ
      hybridization (FISH). Imaging revealed a dense biofilm structure with
      interstitial voids and channels; rods and cocci were interspersed throughout the
      biofilm, indicating bacterial coexistence in close proximity. FISH revealed
      staphylococci and enterococci adjacent to each other and also to the
      Enterobacter, distinguishable by its rod morphology. These studies show that
      different species can co-operatively form mature biofilms on mesh but that the
      relative abundance of a species within the biofilm may vary over time.

PMID- 22364204
TI  - Extracellular nucleic acids in maternal circulation as potential biomarkers for
      placental insufficiency.
AB  - Since the placenta is being continuously remodeled during normal placental
      development, extracellular nucleic acids of both fetal and placental origin,
      packed into either trophoblast-derived apoptotic bodies or shedding
      syncytiotrophoblast microparticles, may be detected in maternal circulation
      during the course of normal gestation. Placental-insufficiency-related pregnancy
      complications have been shown to be associated with excessive placental
      trophoblast apoptosis and shedding of placenta debris. Recent advances in the
      field are reviewed with a focus on the diagnostic potential of particular
      molecular biomarkers and their eventual implementation in the currently used
      predictive and diagnostic algorithms for placental-insufficiency-related
      pregnancy complications.

PMID- 22364208
TI  - The mechanism of alkene addition to a nickel bis(dithiolene) complex: the role of
      the reduced metal complex.
AB  - The binding of an alkene by Ni(tfd)(2) [tfd = S(2)C(2)(CF(3))(2)] is one of the
      most intriguing ligand-based reactions. In the presence of the anionic, reduced
      metal complex, the primary product is an interligand adduct, while in the absence
      of the anion, dihydrodithiins and metal complex decomposition products are
      preferred. New kinetic (global analysis) and computational (DFT) data explain the
      crucial role of the anion in suppressing decomposition and catalyzing the
      formation of the interligand product through a dimetallic complex that appears to
      catalyze alkene addition across the Ni-S bond, leading to a lower barrier for the
      interligand adduct.

PMID- 22364210
TI  - Nanoscale pumping of water by AC electric fields.
AB  - Using molecular dynamics simulations we demonstrate pumping of water through a
      carbon nanotube by time-dependent electric fields. The fields are generated by
      electrodes with oscillating charges in a broad gigahertz frequency range that are
      attached laterally to the tube. The key ingredient is a phase shift between the
      electrodes to break the spatiotemporal symmetry. A microscopic theory based on a
      polarization-dragging mechanism accounts quantitatively for our numerical
      findings.

PMID- 22364209
TI  - Intimate partner violence among HIV-infected crack cocaine users.
AB  - HIV-infected crack cocaine users are at high risk for HIV transmission and
      disease progression because they encounter difficulty practicing safe sex,
      entering and remaining in HIV care, and taking antiretroviral therapy (ART). We
      hypothesized intimate partner violence (IPV) occurs frequently in this population
      and contributes to these shortcomings. From December 2006 to April 2010 inpatient
      HIV-infected crack users were recruited from Grady Memorial (Atlanta, GA) and
      Jackson Memorial Hospitals (Miami, FL). Participants were screened for IPV using
      a 5-item tool that was adapted from a previously validated instrument, the STaT.
      IPV survivors were questioned about support service utilization. Multivariable
      analysis was conducted to evaluate the association between IPV and unprotected
      sexual intercourse and sexually transmitted infection (STI) diagnosis in the
      prior 6 months, use of outpatient HIV care in the past year, and current ART use.
      We enrolled 343 participants, the majority African Americans of low socioeconomic
      status. The estimated IPV prevalence was 56%, highest in women (68%) and gay,
      bisexual, and transgendered men (71%). In multivariable analysis, IPV was
      associated with diminished ART use (adjusted prevalence ratios [adjPRs] 0.57; 95%
      confidence interval [CI] 0.41-0.80), unprotected sexual intercourse (adjPR 1.34;
      95% CI 1.08-1.68) and STI diagnosis in the prior 6 months (adjPR 3.49; 95% CI
      1.60-7.62). After experiencing abuse, IPV survivors most commonly turned to
      emergency services; however, 38% reported not using any supportive services. This
      study highlights that IPV occurs frequently among HIV-infected crack users and is
      associated with outcomes known to facilitate HIV transmission and disease
      progression. Reduced utilization of outpatient HIV care, ART nonadherence, and
      new STI diagnoses in this population should trigger IPV screening and support
      services referral.

PMID- 22364211
TI  - An epigenomic mechanism in retinoblastoma: the end of the story?
AB  - The role that retinoblastoma has played in our understanding of cancer biology
      could hardly have been imagined 40 years ago when this disease was a rare
      curiosity, of interest primarily because of its variable laterality, occasional
      dominant inheritance, frequent lethality and embyronal origin. The discovery of
      its cause (biallelic loss of RB1) did not offer insight to improved management.
      However, the recent discovery of aberrant expression of the gene encoding spleen
      tyrosine kinase (SYK) subsequent to widespread methylation abnormalities in
      retinoblastoma suggests a potential new therapy for the disease. There is more to
      the story, however.

PMID- 22364212
TI  - The balance of the immune system between T cells and NK cells in miscarriage.
AB  - Immunological dysfunction has been proposed to explain the etiology of recurrent
      pregnancy loss (RPL). The immunological environment differs between the decidua
      basalis and decidua parietalis, and also between RPL cases with normal fetal
      chromosomes and those with abnormal fetal chromosomes. The problem with analyzing
      decidual tissues from spontaneous abortions is that cause versus effect phenomena
      are difficult to distinguish. Recent data show that the immune system in a late
      stage miscarriage is completely different from that in an early-stage
      miscarriage. If immunocompetent cells can cause RPL, the immunological
      environment may be a causative factor, especially in an early-stage miscarriage,
      at the decidua basalis, and/or in cases of RPL with a normal embryo. Careful
      examination of the immune system at the decidua basalis in an early-stage
      miscarriage in RPL cases with normal fetal chromosomes may reveal useful
      information. This paper aimed at finding a cause of RPL by analyzing the balance
      of the immune system between T cells and NK cells in an early-stage miscarriage.

PMID- 22364214
TI  - Can experimental pharmacology be always applied to human nutrition?
AB  - Randomized clinical trials are the gold standard of pharmacology and are the only
      way to provide solid and evidence-based data. However, they are difficult to
      apply to nutrition-based settings. This article outlines the major differences
      between pharmacology and nutrition research and indicates some potential pathways
      to follow during claim building.

PMID- 22364215
TI  - Challenges to nurse prescribers of a no-antibiotic prescribing strategy for
      managing self-limiting respiratory tract infections.
AB  - AIMS: To report a qualitative study of the experiences of nurse prescribers in
      managing patients with self-limiting respiratory tract infections. BACKGROUND:
      Patients frequently attend primary care with respiratory tract infections.
      Although a no-prescribing strategy is recommended for these consultations,
      general practitioners frequently prescribe antibiotics, citing non-clinical
      reasons such as patient pressure. Nurses increasingly manage people with
      respiratory tract infections, but research has not yet explored their experiences
      within such consultations. DESIGN: Semi-structured interviews and focus groups.
      METHODS: Fifteen semi-structured interviews and three focus groups (n=5, n=4, and
      n=12) with a purposive sample of nurse prescribers (n=34) and other non-medical
      prescribers (n=2) were conducted between November 2009-November 2010. A
      qualitative approach was used to develop conceptual categories from the dataset,
      and emerging themes were explored in subsequent interviews/focus groups.
      FINDINGS: Although participants reported experiencing numerous challenges within
      these consultations, they believed that they possessed some of the communication
      skills to deal effectively with patients without prescribing antibiotics.
      Participants reported that protocols supported their decision-making and welcomed
      the benefits of peer support in dealing with 'demanding' patients. However, the
      newness of nurses and other non-medical prescribers to the prescribing role meant
      that some were cautious in dealing with patients with respiratory tract
      infections. CONCLUSION: Training for nurses and other non-medical prescribers
      should focus on building their confidence and skills to manage people with
      respiratory tract infections without recourse to antibiotics. Further work should
      seek to explore which strategies are most effective in managing respiratory tract
      infections while maintaining patient satisfaction with care.

PMID- 22364217
TI  - hTERT mutations associated with idiopathic pulmonary fibrosis affect telomerase
      activity, telomere length, and cell growth by distinct mechanisms.
AB  - Telomerase is a ribonucleoprotein reverse transcriptase (RT) that synthesizes
      specific DNA repeats, or telomeric DNA, at the ends of chromosomes. Telomerase is
      minimally composed of a protein subunit, TERT, and an RNA component, TR. Aberrant
      telomerase activity has been associated with most human cancers and several
      premature aging diseases, such as idiopathic pulmonary fibrosis (IPF), a chronic,
      progressive, and fatal lung disease characterized by alveolar epithelial cell
      damage and fibrosis. Our study focuses on three hTERT mutations that were
      identified in a subset of patients with IPF, in which these patients also
      exhibited shorter telomeres compared with age-matched controls. We characterized
      how three IPF-associated hTERT mutations, V144M, R865C, and R865H, affected
      telomerase function both in vitro and in human cells. We demonstrated that the
      R865 residue is crucial for repeat addition processivity and thus telomere
      synthesis in telomerase-positive 293 cells and telomerase-negative BJ cells,
      consistent with its location in the hTERT nucleotide-binding motif. In contrast,
      while the V144M mutant did not exhibit any biochemical defects, this mutant was
      unable to elongate telomeres in human cells. As a result, our studies have
      identified hTERT V144 and R865 as two critical residues required for proper
      telomerase function in cells. Together, this may explain how inherited hTERT
      mutations can lead to shortened telomeres in patients with IPF and, thus, provide
      further insight into the role of naturally occurring telomerase mutations in the
      pathophysiology of certain age-related disease states.

PMID- 22364218
TI  - Coronin 1C harbours a second actin-binding site that confers co-operative binding
      to F-actin.
AB  - Dynamic rearrangement of actin filament networks is critical for cell motility,
      phagocytosis and endocytosis. Coronins facilitate these processes, in part, by
      their ability to bind F-actin (filamentous actin). We previously identified a
      conserved surface-exposed arginine (Arg(30)) in the beta-propeller of Coronin 1B
      required for F-actin binding in vitro and in vivo. However, whether this finding
      translates to other coronins has not been well defined. Using quantitative actin
      binding assays, we show that mutating the equivalent residue abolishes F-actin
      binding in Coronin 1A, but not Coronin 1C. By mutagenesis and biochemical
      competition, we have identified a second actin-binding site in the unique region
      of Coronin 1C. Interestingly, leading-edge localization of Coronin 1C in
      fibroblasts requires the conserved site in the beta-propeller, but not the site
      in the unique region. Furthermore, in contrast with Coronin 1A and Coronin 1B,
      Coronin 1C displays highly co-operative binding to actin filaments. In the
      present study, we highlight a novel mode of coronin regulation, which has
      implications for how coronins orchestrate cytoskeletal dynamics.

PMID- 22364219
TI  - Presence of nano-sized silica during in vitro digestion of foods containing
      silica as a food additive.
AB  - The presence, dissolution, agglomeration state, and release of materials in the
      nano-size range from food containing engineered nanoparticles during human
      digestion is a key question for the safety assessment of these materials. We used
      an in vitro model to mimic the human digestion. Food products subjected to in
      vitro digestion included (i) hot water, (ii) coffee with powdered creamer, (iii)
      instant soup, and (iv) pancake which either contained silica as the food additive
      E551, or to which a form of synthetic amorphous silica or 32 nm SiO(2) particles
      were added. The results showed that, in the mouth stage of the digestion, nano
      sized silica particles with a size range of 5-50 and 50-500 nm were present in
      food products containing E551 or added synthetic amorphous silica. However,
      during the successive gastric digestion stage, this nano-sized silica was no
      longer present for the food matrices coffee and instant soup, while low amounts
      were found for pancakes. Additional experiments showed that the absence of nano
      sized silica in the gastric stage can be contributed to an effect of low pH
      combined with high electrolyte concentrations in the gastric digestion stage.
      Large silica agglomerates are formed under these conditions as determined by DLS
      and SEM experiments and explained theoretically by the extended DLVO theory.
      Importantly, in the subsequent intestinal digestion stage, the nano-sized silica
      particles reappeared again, even in amounts higher than in the saliva (mouth)
      digestion stage. These findings suggest that, upon consumption of foods
      containing E551, the gut epithelium is most likely exposed to nano-sized silica.

PMID- 22364220
TI  - Hexoctahedral Au nanocrystals with high-index facets and their optical and
      surface-enhanced Raman scattering properties.
AB  - Au nanocrystals (NCs) with an unprecedented hexoctahedral structure enclosed
      exclusively by high-index {321} facets have been prepared for the first time.
      Manipulating the NC growth kinetics by controlling the amount of reductant and
      the reaction temperature in the presence of a suitable surfactant was the key
      synthetic lever for controlling the morphology of the Au NCs. The hexoctahedral
      Au NCs exhibited efficient optical and surface-enhanced Raman scattering
      activities due to their unique morphological characteristics.

PMID- 22364221
TI  - Radiographic assessments on prevalence and technical quality of endodontically
      treated teeth in the Finnish population, aged 30 years and older.
AB  - OBJECTIVE: To assess the prevalence and technical quality of endodontic treatment
      (ET) in Finland by panoramic radiography. MATERIALS AND METHODS: As part of the
      Finnish nationwide Health 2000 Survey, panoramic radiographs of 5244 dentate
      subjects, aged 30-95 years, were analyzed. The criterion for a technically
      adequate ET was a distance from the root filling to the root apex of <=3 mm.
      RESULTS: Sixty-one per cent of subjects had one or more teeth with ET. ET was
      more prevalent in older subjects and among women. Of all teeth (n = 120 250), 7%
      had had ET, the percentages being greatest for molars and premolars. Technical
      quality was adequate in 47% of all ET, in 71% of anterior teeth, in 51% of
      premolars and in 25% of molars. CONCLUSIONS: Prevalence and technical quality of
      endodontic treatment in Finland are comparable to that reported elsewhere, but
      are still calling for improvement in endodontic treatment, especially regarding
      molars.

PMID- 22364222
TI  - From InSb nanowires to nanocubes: looking for the sweet spot.
AB  - High aspect ratios are highly desired to fully exploit the one-dimensional
      properties of indium antimonide nanowires. Here we systematically investigate the
      growth mechanisms and find parameters leading to long and thin nanowires.
      Variation of the V/III ratio and the nanowire density are found to have the same
      influence on the "local" growth conditions and can control the InSb shape from
      thin nanowires to nanocubes. We propose that the V/III ratio controls the droplet
      composition and the radial growth rate and these parameters determine the
      nanowire shape. A sweet spot is found for nanowire interdistances around 500 nm
      leading to aspect ratios up to 35. High electron mobilities up to 3.5 * 10(4)
      cm(2) V(-1) s(-1) enable the realization of complex spintronic and topological
      devices.

PMID- 22364223
TI  - Methylglyoxal causes structural and functional alterations in adipose tissue
      independently of obesity.
AB  - CONTEXT: Adipose tissue is one of the first organs to develop insulin resistance
      even with moderate BMI. However, the contribution of developing hyperglycaemia
      and concomitant methylglyoxal increment to tissue dysfunction during type 2
      diabetes progression was not addressed before. METHODS: Young and aged Wistar and
      Goto-Kakizaki rats (non-obese model of type 2 diabetes) and a group of MG-treated
      W rats were used to investigate the chronic effects of hyperglycaemia and ageing
      and specifically MG-induced mechanisms. RESULTS: Diabetic and aged rats showed
      decreased adipose tissue irrigation and interstitial hypoxia. Hyperglycaemia of
      diabetic rats leaded to fibrosis and accumulation of PAS-positive components,
      exacerbated in aged animals, which also showed decreased hipoadiponectinemia,
      increased MCP-1 expression and macrophage infiltration to glycated fibrotic
      regions. MG leaded to increased free fatty acids, hipoadiponectinemia, decreased
      irrigation, hypoxia and macrophage recruitment for glycated fibrotic regions.
      CONCLUSIONS: MG contributes to dysfunction of adipose tissue during type 2
      diabetes progression.

PMID- 22364224
TI  - Seroprevalence and risk factors of bovine herpesvirus 1 infection in cattle herds
      in the state of Parana, Brazil.
AB  - Epidemiological data describing bovine herpesvirus 1 (BoHV-1) infection in
      Brazilian cattle herds are scarce. A cross-sectional study was conducted in the
      state of Parana between December 2001 and July 2002 with the objective of
      estimating the apparent prevalence of BoHV-1-seropositive herds and animals and
      identifying the potential risk factors for infection in farms with breeding
      animals in the state of Parana in Southern Brazil. The state was divided into
      seven regions based on the livestock production dynamics of the different areas.
      Sampling was performed in two stages. Initially, herds were randomly selected,
      followed by a random selection of animals within the selected herds. Blood
      samples were collected from 14803 females, aged >=24 months, from 2018 BoHV-1 non
      vaccinated herds. Serum samples were tested for antibodies against BoHV-1 using
      an indirect enzyme-linked immunosorbent assay (ELISA). The apparent prevalence of
      seropositivity in the herds and animals in Parana was 71.3% (95% CI: 69.3-73.3)
      and 59.0% (95% CI: 56.2-61.8), respectively. Multiple logistic regression
      analysis revealed that risk factors associated with the presence of the infection
      were as follows: beef herds [OR = 1.58 (1.12-2.23)], natural service [OR = 1.48
      (1.02-2.14)], purchase of animals [OR = 1.90 (1.52-2.37)], pasture rental [OR =
      2.24 (1.51-3.33)], existence of calving pens [OR = 1.56 (1.20-2.03)] and records
      of abortion in the last 12 months [OR = 1.45 (1.08-1.95)]. These results indicate
      that BoHV-1 infection is widespread in the state of Parana.

PMID- 22364225
TI  - A new class of lithium and sodium rechargeable batteries based on selenium and
      selenium-sulfur as a positive electrode.
AB  - A new class of selenium and selenium-sulfur (Se(x)S(y))-based cathode materials
      for room temperature lithium and sodium batteries is reported. The structural
      mechanisms for Li/Na insertion in these electrodes were investigated using pair
      distribution function (PDF) analysis. Not only does the Se electrode show
      promising electrochemical performance with both Li and Na anodes, but the
      additional potential for mixed Se(x)S(y) systems allows for tunable electrodes,
      combining the high capacities of S-rich systems with the high electrical
      conductivity of the d-electron containing Se. Unlike the widely studied Li/S
      system, both Se and Se(x)S(y) can be cycled to high voltages (up to 4.6 V)
      without failure. Their high densities and voltage output offer greater volumetric
      energy densities than S-based batteries, opening possibilities for new energy
      storage systems that can enable electric vehicles and smart grids.

PMID- 22364226
TI  - NOD/scid IL-2Rg(null) mice: a preclinical model system to evaluate human
      dendritic cell-based vaccine strategies in vivo.
AB  - BACKGROUND: To date very few systems have been described for preclinical
      investigations of human cellular therapeutics in vivo. However, the ability to
      carry out comparisons of new cellular vaccines in vivo would be of substantial
      interest for design of clinical studies. Here we describe a humanized mouse model
      to assess the efficacy of various human dendritic cell (DC) preparations. Two
      reconstitution regimes of NOD/scid IL2Rg(null) (NSG) mice with adult human
      peripheral blood mononuclear cells (PBMC) were evaluated for engraftment using 4
      week and 9-week schedules. This led to selection of a simple and rapid protocol
      for engraftment and vaccine evaluation that encompassed 4 weeks. METHODS: NSG
      recipients of human PBMC were engrafted over 14 days and then vaccinated twice
      with autologous DC via intravenous injection. Three DC vaccine formulations were
      compared that varied generation time in vitro (3 days versus 7 days) and signals
      for maturation (with or without Toll-like receptor (TLR)3 and TLR7/8 agonists)
      using MART-1 as a surrogate antigen, by electroporating mature DC with in vitro
      transcribed RNA encoding full length protein. After two weekly vaccinations, the
      splenocyte populations containing human lymphocytes were recovered 7 days later
      and assessed for MART-1-specific immune responses using MHC-multimer-binding
      assays and functional assessment of specific killing of melanoma tumor cell
      lines. RESULTS: Human monocyte-derived DC generated in vitro in 3 days induced
      better MART-1-specific immune responses in the autologous donor T cells present
      in the humanized NSG mice. Moreover, consistent with our in vitro observations,
      vaccination using mature DC activated with TLR3 and TLR7/8 agonists resulted in
      enhanced immune responses in vivo. These findings led to a ranking of the DC
      vaccine effects in vivo that reflected the hierarchy previously found for these
      mature DC variations in vitro. CONCLUSIONS: This humanized mouse model system
      enables comparisons among different DC vaccine types to be rapidly assessed in
      vivo. In addition, ex vivo analyses of human CD3+ T cells recovered from the
      spleens of these mice are also possible, including studies on lymphocyte subsets,
      Th1/Th2 polarization, presence of regulatory T cells and the impact of DC
      vaccination on their functions.

PMID- 22364228
TI  - Palladium-catalyzed divergent reactions of 1,6-enyne carbonates: synthesis of
      vinylidenepyridines and vinylidenepyrrolidines.
AB  - A method for preparing five- or six-membered heterocyclic compounds from enyne
      carbonates via palladium catalysis was developed. Enyne carbonates were
      transformed into 3-vinylidene-1-tosylpyridines 2 in the presence of PdI(2) as the
      catalyst. Using Pd(dba)(2) as the catalyst, 3-vinylidene-1-tosylpyrrolidines 3
      were obtained. Further functionalizations of compounds 3 were carried out in a
      one-pot manner.

PMID- 22364227
TI  - Extended-spectrum beta-lactamase (ESBL) in Danish clinical isolates of
      Escherichia coli and Klebsiella pneumoniae: prevalence, beta-lactamase
      distribution, phylogroups, and co-resistance.
AB  - BACKGROUND: Most Gram-negative community-acquired and nosocomial infections are
      caused by Escherichia coli and Klebsiella pneumoniae, among which increasing
      resistance due to extended-spectrum beta-lactamase (ESBL) is a major problem. We
      present data from the first Danish nationwide prevalence study on ESBL-producing
      E. coli, K. pneumoniae, and Proteus mirabilis in blood and urine cultures from
      hospitals and the community. METHODS: During September and October 2007, 13 of 15
      Danish departments of clinical microbiology collected data and strains.
      Confirmatory ESBL test-positive isolates were sent to a central laboratory for
      species and ESBL-phenotype confirmation, extended susceptibility testing,
      phylogenetic grouping of E. coli strains, and ESBL gene characterization.
      RESULTS: During the study, blood samples from 18,259 patients and urine samples
      from 47,504 patients were subjected to culture. Among 14,674 cultured isolates,
      352 were confirmed to be ESBL-producers. Thus, the crude ESBL prevalence was 2.4%
      (range 1.5% of E. coli in community urine to 6.6% of K. pneumoniae in hospital
      urine). An average of 7.2 ESBL-producers per 100,000 consumed bed-days was
      calculated. Of the 352 reported ESBL-producers, 205 E. coli, 73 K. pneumoniae,
      and 1 P. mirabilis, were available for testing. CTX-M enzymes dominated, both in
      hospitals and in the community, occurring in 92% of E. coli and 88% of K.
      pneumoniae, and with CTX-M-15 constituting 60% and 77%, respectively.
      CONCLUSIONS: Compared to 2003 data the ESBL prevalence in Denmark has increased
      significantly. In the ESBL-producers, reduced susceptibility towards both
      gentamicin and ciprofloxacin was seen among 43% E. coli and 55% K. pneumoniae,
      leaving clinicians in these cases with only a carbapenem for the treatment of
      serious infections. Part of this study was presented at the 20(th) European
      Congress of Clinical Microbiology and Infectious Diseases, abstract P-1617.

PMID- 22364229
TI  - Inhibition of adrenergic human prostate smooth muscle contraction by the
      inhibitors of c-Jun N-terminal kinase, SP600125 and BI-78D3.
AB  - BACKGROUND AND PURPOSE alpha(1) -Adrenoceptor-induced contraction of prostate
      smooth muscle is mediated by calcium- and Rho kinase-dependent mechanisms. In
      addition, other mechanisms, such as activation of c-jun N-terminal kinase (JNK)
      may be involved. Here, we investigated whether JNK participates in alpha(1)
      adrenoceptor-induced contraction of human prostate smooth muscle. EXPERIMENTAL
      APPROACH Prostate tissue was obtained from patients undergoing radical
      prostatectomy. Effects of the JNK inhibitors SP600125 (50 uM) and BI-78D3 (30 uM)
      on contractions induced by phenylephrine, noradrenaline and electric field
      stimulation (EFS) were studied in myographic measurements. JNK activation by
      noradrenaline (30 uM) and phenylephrine (10 uM), and the effects of JNK
      inhibitors of c-Jun phosphorylation were assessed by Western blot analyses with
      phospho-specific antibodies. Expression of JNK was studied by
      immunohistochemistry and fluorescence double staining. KEY RESULTS The JNK
      inhibitors SP600125 and BI-78D3 reduced phenylephrine- and noradrenaline-induced
      contractions of human prostate strips. In addition, SP600125 reduced EFS-induced
      contraction of prostate strips. Stimulation of prostate tissue with noradrenaline
      or phenylephrine in vitro resulted in activation of JNK. Incubation of prostate
      tissue with SP600125 or BI-78D3 reduced the phosphorylation state of c-Jun.
      Immunohistochemical staining demonstrated the expression of JNK in smooth muscle
      cells of human prostate tissue. Fluorescence staining showed that alpha(1A)
      adrenoceptors and JNK are expressed in the same cells. CONCLUSIONS AND
      IMPLICATIONS Activation of JNK is involved in alpha(1)-adrenoceptor-induced
      prostate smooth muscle contraction. Models of alpha(1)-adrenoceptor-mediated
      prostate smooth muscle contraction should include this JNK-dependent mechanism.

PMID- 22364230
TI  - Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of
      molecular weight of PEG-PCL diblock copolymer on the in vitro and in vivo
      performance of micelles.
AB  - In the present study, six different molecular weight diblock copolymer of methoxy
      poly (ethylene glycol)-b-poly (epsilon-caprolactone) (MPEG-PCL) were synthesized
      and characterized and was used for fabrication of etoposide-loaded micelles by
      nanoprecipitation technique. The particle size and percentage drug entrapment of
      prepared micelles were found to be dependent on the molecular weight of PCL block
      and drug to polymer ratio. The maximum drug loading of 5.32% was found in
      micellar formulation MPEG5000-PCL10000, while MPEG2000-PCL2000 exhibited 2.73% of
      maximum drug loading. A variation in the fixed aqueous layer thickness and PEG
      surface density of micellar formulations was attributed to difference in MPEG
      molecular weight and interaction of PEG and PCL block of copolymer. The MPEG2000
      PCL2000 micelles demonstrated poor in vitro stability among other micellar
      formulations, due to its interaction with bovine serum albumin and immediate
      release of drug from micelles. Furthermore, plain etoposide and MPEG2000-PCL2000
      micelles exhibited greater extent of hemolysis, due to presence of surfactants
      and faster release of drug from micelles, respectively. The biodistribution
      studies carried out on Ehrlich ascites tumor-bearing Balb/C mice confirmed higher
      accumulation of etoposide-loaded micellar formulation at tumor site compared to
      plain etoposide due to enhanced permeability and retention effect.

PMID- 22364231
TI  - Bacterial diversity in suspected prosthetic joint infections: an exploratory
      study using 16S rRNA gene analysis.
AB  - Formation of biofilm is a prominent feature of prosthetic joint infections (PJIs)
      and constitutes a challenge to current sampling procedures and culture practices.
      Molecular techniques have a potential for improving diagnosis of biofilm-adapted,
      slow-growing and non-culturable bacteria. In this exploratory study we
      investigated the bacterial diversity in specimens from 22 patients clinically
      suspected of having PJIs. Bacteriological cultures were performed according to
      standard practice. A total of 55 specimens from 25 procedures ('specimen sets')
      were submitted to broad range 16S rRNA gene PCR, cloning, sequencing and
      phylogenetic analysis. More than 40 bacterial taxa within six phyla were
      identified in 14 specimen sets originating from 11 patients. Direct observation
      of biofilm was made in selected specimens by fluorescence in situ hydridization.
      16S rRNA gene analysis and bacteriological cultures were concordant for 15/25
      specimen sets (60%; five positive, 10 negative); additional taxa were detected in
      four sets by gene analysis, and discrepant results were obtained for six sets,
      five of which were negative on culture. Polymicrobial communities were revealed
      in 9/14 sets by gene analysis and 1/10 sets by culture (P < 0.05). Although our
      study was not conclusive, these findings are consistent with a primary role of
      biofilm formation in PJIs.

PMID- 22364232
TI  - Changes of NK cells in preeclampsia.
AB  - The regulation of uterine and circulating peripheral blood natural killer (NK)
      cells has been associated with reproductive immunology such as recurrent
      pregnancy losses, implantation failures, or preeclampsia. Preeclampsia is a
      hypertensive disorder of pregnancy characterized by increased blood pressure
      accompanied by proteinuria and is a major cause of maternal and fetal mortality.
      Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell
      cytotoxicity and cytokine production. The relation of NCRs to reproduction is not
      fully characterized yet. The different profile of NCRs expression may suggest
      presence of abnormal regulation of NK cell in women with reproductive failures.
      Pregnant women with preeclampsia carry immunological abnormalities of NCRs on
      peripheral blood NK cells during pregnancy. The lower expression of NKp46(+) NK
      cells in women with preeclampsia may account for the higher production of NK1
      cytokine that is known as NK1 shift in pregnant women with preeclampsia.
      Evaluation of NKp46 on peripheral blood NK cells may be applicable to find the
      onset of preeclampsia. In this review, various expressions of NK cell surface
      markers including NCRs on NK cells, NK cell cytotoxicity, and production of
      cytokines and angiogenic factors by NK cells were reviewed in relation to
      preeclampsia.

PMID- 22364234
TI  - Full surface embedding of gold clusters on silicon nanowires for efficient
      capture and photothermal therapy of circulating tumor cells.
AB  - We report on rapid thermal chemical vapor deposition growth of silicon nanowires
      (Si NWs) that contain a high density of gold nanoclusters (Au NCs) with a uniform
      coverage over the entire length of the nanowire sidewalls. The Au NC-coated Si
      NWs with an antibody-coated surface obtain the unique capability to capture
      breast cancer cells at twice the highest efficiency currently achievable (~88% at
      40 min cell incubation time) from a nanostructured substrate. We also found that
      irradiation of breast cancer cells captured on Au NC-coated Si NWs with a near
      infrared light resulted in a high mortality rate of these cancer cells, raising a
      fine prospect for simultaneous capture and plasmonic photothermal therapy for
      circulating tumor cells.

PMID- 22364233
TI  - Systems-level analysis of age-related macular degeneration reveals global
      biomarkers and phenotype-specific functional networks.
AB  - Please see related commentary: http://www.biomedcentral.com/1741
      7015/10/21/abstract BACKGROUND: Age-related macular degeneration (AMD) is a
      leading cause of blindness that affects the central region of the retinal
      pigmented epithelium (RPE), choroid, and neural retina. Initially characterized
      by an accumulation of sub-RPE deposits, AMD leads to progressive retinal
      degeneration, and in advanced cases, irreversible vision loss. Although genetic
      analysis, animal models, and cell culture systems have yielded important insights
      into AMD, the molecular pathways underlying AMD's onset and progression remain
      poorly delineated. We sought to better understand the molecular underpinnings of
      this devastating disease by performing the first comparative transcriptome
      analysis of AMD and normal human donor eyes. METHODS: RPE-choroid and retina
      tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11
      potential pre-AMD human donor eyes. Transcriptome profiles were generated for
      macular and extramacular regions, and statistical and bioinformatic methods were
      employed to identify disease-associated gene signatures and functionally enriched
      protein association networks. Selected genes of high significance were validated
      using an independent donor cohort. RESULTS: We identified over 50 annotated genes
      enriched in cell-mediated immune responses that are globally over-expressed in
      RPE-choroid AMD phenotypes. Using a machine learning model and a second donor
      cohort, we show that the top 20 global genes are predictive of AMD clinical
      diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid
      that delineate the advanced AMD phenotypes, neovascular AMD and geographic
      atrophy. Moreover, we identified a graded increase of transcript levels in the
      retina related to wound response, complement cascade, and neurogenesis that
      strongly correlates with decreased levels of phototransduction transcripts and
      increased AMD severity. Based on our findings, we assembled protein-protein
      interactomes that highlight functional networks likely to be involved in AMD
      pathogenesis. CONCLUSIONS: We discovered new global biomarkers and gene
      expression signatures of AMD. These results are consistent with a model whereby
      cell-based inflammatory responses represent a central feature of AMD etiology,
      and depending on genetics, environment, or stochastic factors, may give rise to
      the advanced AMD phenotypes characterized by angiogenesis and/or cell death.
      Genes regulating these immunological activities, along with numerous other genes
      identified here, represent promising new targets for AMD-directed therapeutics
      and diagnostics.

PMID- 22364237
TI  - Gum chewing modulates heart rate variability under noise stress.
AB  - OBJECTIVE: Gum chewing may relieve stress, although this hypothesis has not been
      proven. Heart-rate variability (HRV) is commonly used to measure stress levels.
      However, it is not known if gum chewing modulates HRV under acute stress. The aim
      of this study was to investigate the effects of gum chewing on HRV under acute
      stress. MATERIALS AND METHODS: A cross-over study involving 47 non-smoking
      healthy subjects, aged 22-27 years, was carried out. The subjects received a
      stress procedure with gum chewing (GS group) and without gum chewing (S group).
      Additionally, the other 20 subjects were allocated to the gum chewing without
      stress group (G group). The GS and S groups were exposed to noise for 5 min (75
      dBA) as stress. Before and after stress exposure/gum chewing, participants
      completed the state portion of the State-Trait Anxiety Inventory (STAI-s) and a
      single Stress Visual Analogue Scale (VAS) measurement. HRV measurement was
      performed before and during stress/gum chewing for 5 min. RESULTS: After the
      stress procedure, VAS score significantly increased in the GS and S groups.
      During the stress procedure, the GS group showed a significantly lower level of
      high frequency (HF) and higher levels of low frequency (LF) and LF/HF than the S
      group. However, there were no significant differences in the scores of the state
      portion of the State-Trait Anxiety Inventory (STAI-s) and VAS between the two
      stress groups. CONCLUSIONS: These findings suggest that gum chewing modulates
      HRV, but may not relieve acute stress caused by noise.

PMID- 22364236
TI  - Tyrosine replacing tryptophan as an anchor in GWALP peptides.
AB  - Synthetic model peptides have proven useful for examining fundamental peptide
      lipid interactions. A frequently employed peptide design consists of a
      hydrophobic core of Leu-Ala residues with polar or aromatic amino acids flanking
      each side at the interfacial positions, which serve to "anchor" a specific
      transmembrane orientation. For example, WALP family peptides (acetyl
      GWW(LA)(n)LWWA-[ethanol]amide), anchored by four Trp residues, have received
      particular attention in both experimental and theoretical studies. A recent
      modification proved successful in reducing the number of Trp anchors to only one
      near each end of the peptide. The resulting GWALP23 (acetyl
      GGALW(5)(LA)(6)LW(19)LAGA-[ethanol]amide) displays reduced dynamics and greater
      sensitivity to lipid-peptide hydrophobic mismatch than traditional WALP peptides.
      We have further modified GWALP23 to incorporate a single tyrosine, replacing W(5)
      with Y(5). The resulting peptide, Y(5)GWALP23 (acetyl-GGALY(5)(LA)(6)LW(19)LAGA
      amide), has a single Trp residue that is sensitive to fluorescence experiments.
      By incorporating specific (2)H and (15)N labels in the core sequence of
      Y(5)GWALP23, we were able to use solid-state NMR spectroscopy to examine the
      peptide orientation in hydrated lipid bilayer membranes. The peptide orients well
      in membranes and gives well-defined (2)H quadrupolar splittings and (15)N/(1)H
      dipolar couplings throughout the core helical sequence between the aromatic
      residues. The substitution of Y(5) for W(5) has remarkably little influence on
      the tilt or dynamics of GWALP23 in bilayer membranes of the phospholipids DOPC,
      DMPC, or DLPC. A second analogue of the peptide with one Trp and two Tyr anchors,
      Y(4,5)GWALP23, is generally less responsive to the bilayer thickness and exhibits
      lower apparent tilt angles with evidence of more extensive dynamics. In general,
      the peptide behavior with multiple Tyr anchors appears to be quite similar to the
      situation when multiple Trp anchors are present, as in the original WALP series
      of model peptides.

PMID- 22364235
TI  - Nitric oxide donor exisulind is an effective inhibitor of murine
      photocarcinogenesis.
AB  - NO-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) have been shown to
      have anti-inflammatory, antiproliferative and apoptosis-inducing effects in tumor
      cells. Herein, we have investigated the effects of NO-exisulind on the growth of
      UVB-induced skin tumor development in a murine model. We found that the topical
      treatment with NO-exisulind significantly reduced UVB-induced tumors in SKH-1
      hairless mice. The tumors/tumor bearing mouse, the number of tumors/mouse and
      tumor volume/mouse decreased significantly (P < 0.05) as compared with vehicle
      treated and UVB-irradiated positive controls. Consistently, NO-exisulind-treated
      animals showed reduced expression of proliferation markers, such as PCNA and
      cyclin D1. These mice also manifested increased expression of proapoptotic Bax
      and decreased expression of antiapoptotic Bcl2 with an increase in the number of
      TUNEL-positive cells in tumors. We also investigated whether NO-exisulind-treated
      tumors are less invasive and progress less efficiently from benign to malignant
      carcinomas. For this, tumors were stained for various epithelial-mesenchymal
      transition (EMT) markers. NO-exisulind decreased the expression of mesenchymal
      markers, such as Fibronectin, N-cadherin, SNAI, Slug and Twist and enhanced the
      epithelial marker E-cadherin. Similarly, UVB-induced phosphorylation of Erk1/2
      and p38 was decreased in NO-exisulind-treated animals. These data suggest that NO
      exisulind reduces tumor growth and inhibits tumor progression by blocking
      proliferation, inducing apoptosis and reducing EMT.

PMID- 22364238
TI  - Phase I clinical trial of oral rosiglitazone in combination with intravenous
      carboplatin in cancer-bearing dogs.
AB  - Rosiglitazone is an FDA-approved peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist and antidiabetic agent in humans that has been investigated
      for its ability to reduce tumor cell growth. The purpose of this study was to
      determine the maximally tolerated dose, peak plasma concentrations and side
      effect profile of oral rosiglitazone when combined with carboplatin in dogs with
      cancer. Rosiglitazone was administered at 6 and 8 mg/m(2) to seven dogs.
      Carboplatin was administered at 240-300 mg/m(2) in combination with
      rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in
      this study were combined with the toxicity data from three dogs previously
      reported in a methodology study. Peak plasma rosiglitazone concentrations varied
      with dose. The dose-limiting toxicity was hepatic at a dose of 8 mg/m(2). Three
      dogs had mild to moderate alanine aminotransferase elevations but no changes in
      total bilirubin, alkaline phosphatase, blood glucose or gamma
      glutamyltranspeptidase values were noted.

PMID- 22364240
TI  - Nanoparticle manipulation by thermal gradient.
AB  - A method was proposed to manipulate nanoparticles through a thermal gradient.
      The motion of a fullerene molecule enclosed inside a (10, 10) carbon nanotube
      with a thermal gradient was studied by molecular dynamics simulations. We created
      a one-dimensional potential valley by imposing a symmetrical thermal gradient
      inside the nanotube. When the temperature gradient was large enough, the
      fullerene sank into the valley and became trapped. The escaping velocities of the
      fullerene were evaluated based on the relationship between thermal gradient and
      thermophoretic force. We then introduced a new way to manipulate the position of
      nanoparticles by translating the position of thermostats with desirable thermal
      gradients. Compared to nanomanipulation using a scanning tunneling microscope or
      an atomic force microscope, our method for nanomanipulation has a great advantage
      by not requiring a direct contact between the probe and the object.

PMID- 22364241
TI  - Controlling the exciton fine structure splitting in CdSe/CdS dot-in-rod
      nanojunctions.
AB  - We demonstrate control and tunability of the exciton fine-structure splitting by
      properly engineering a nanojunction consisting of a CdSe nanocrystal core and an
      asymmetric rod-like CdS shell. Samples with small core and/or thick rod diameters
      exhibit a strongly reduced fine-structure splitting resulting from a reduced
      electron-hole exchange interaction. These results shed light onto the electronic
      configuration of such nanosystems and, apart from being of fundamental interest,
      could enable the use of colloidal nanocrystals as a source of entangled photons.

PMID- 22364243
TI  - Facile solvothermal synthesis of porous cubic Cu microparticles as copper
      catalysts for Rochow reaction.
AB  - Porous cubic Cu microparticles were synthesized by a facile solvothermal method
      using Cu(CH(3)COO)(2).H(2)O as the Cu precursor and NaOH in a solution containing
      ethanol, ethylene glycol, and water. The synthesis conditions were investigated
      and a growth process of porous cubic Cu microparticles was proposed. The
      catalytic properties of the porous Cu microparticles as model copper catalysts
      for Rochow reaction were explored. The samples were characterized by X-ray
      diffraction, scanning electron microscopy, transmission electron microscopy,
      thermogravimetric analysis, temperature-programmed reduction, and nitrogen
      adsorption. It was found that the morphology and structure of the porous cubic Cu
      microparticles are highly dependent on the reaction time and temperature as well
      as on the amount of reactants added. Compared to the commercial Cu microparticles
      with irregular morphology and dense internal structure, porous cubic Cu
      microparticles show much higher dimethyldichlorosilane selectivity and Si
      conversion via Rochow reaction, which are attributed to the enhanced formation of
      active Cu(x)Si phase and gas transportation in the presence of the pore system
      within microparticles, demonstrating the significance of the pore structure of
      the copper catalysts in catalytic reactions of organosilane synthesis.

PMID- 22364244
TI  - The use of failure mode and effect analysis in a radiation oncology setting: the
      Cancer Treatment Centers of America experience.
AB  - Delivering radiation therapy in an oncology setting is a high-risk process where
      system failures are more likely to occur because of increasing utilization,
      complexity, and sophistication of the equipment and related processes. Healthcare
      failure mode and effect analysis (FMEA) is a method used to proactively detect
      risks to the patient in a particular healthcare process and correct potential
      errors before adverse events occur. FMEA is a systematic, multidisciplinary team
      based approach to error prevention and enhancing patient safety. We describe our
      experience of using FMEA as a prospective risk-management technique in radiation
      oncology at a national network of oncology hospitals in the United States,
      capitalizing not only on the use of a team-based tool but also creating momentum
      across a network of collaborative facilities seeking to learn from and share best
      practices with each other. The major steps of our analysis across 4 sites and
      collectively were: choosing the process and subprocesses to be studied,
      assembling a multidisciplinary team at each site responsible for conducting the
      hazard analysis, and developing and implementing actions related to our findings.
      We identified 5 areas of performance improvement for which risk-reducing actions
      were successfully implemented across our enterprise. 

PMID- 22364245
TI  - Googling for ghosts: a meditation on writers' block, mourning, and the Holocaust.
AB  - The author describes her father's experience of being a Holocaust survivor and
      how his unfinished mourning contributed to her struggle with muteness, her own
      story being dwarfed by the magnitude of her father's losses. When her non-Jewish
      mother is chosen to be honored by Yad Vashem, the ceremony proves unexpectedly
      powerful. The witnessing by community, through the Internet, helps dissolve the
      shame and isolation, heals some of the trauma, and promotes greater psychological
      freedom. In creating this paper, the author memorializes her parents and her lost
      relatives, and succeeds in working through much that had haunted her.

PMID- 22364246
TI  - Whereof one cannot speak: conducting psychoanalysis online.

PMID- 22364247
TI  - The couch as icon.
AB  - The couch has always been an integral part of psychoanalytic practice. It has
      even become a cultural icon representing psychoanalysis itself. However, minimal
      evidence exists in the psychoanalytic literature that using the couch is
      necessary or even necessarily helpful to establish a psychoanalytic process and
      conduct an analysis. Furthermore, it can potentially be harmful to patients such
      as those who have experienced early loss and trauma or who have significant ego
      organizational problems. Therefore, the use of the couch per se does not seem
      well suited as a defining criterion of psychoanalysis. To the extent that it may
      be clinically valuable, the use of the couch should be more carefully considered
      and critically examined.

PMID- 22364248
TI  - Psychoanalysis and psychiatry in the twenty-first century: historical
      reflections.

PMID- 22364249
TI  - Expanding the single-case study: a proposed psychoanalytic research program.
AB  - This paper offers a proposed program of research using single-case time-series
      methods that can be used by practicing clinicians. The paper is written for
      psychodynamically oriented clinicians who want to get involved in psychotherapy
      research and make contributions to the scientific literature. How to measure
      treatment outcomes and psychodynamic constructs are discussed. With few
      exceptions, conducting single-case time-series research using psychodynamic
      psychotherapy has far more advantages than disadvantages.

PMID- 22364250
TI  - Political humiliation, object use, and psychological changes in the life of
      Malcolm X.
AB  - This article examines and describes the traumatic effects of political
      humiliation in the life of Malcolm X, and the psychosocial changes exhibited in
      his moving from being snared by the talons of racism to a greater sense of
      freedom and flexibility in working with a wide variety of people. Malcolm X's
      suffering and psychosocial changes are framed in terms of object relating and
      use, as well as by his search for a transformational object that would restore
      and secure his self-worth and efficacy.

PMID- 22364253
TI  - Environmental isolation and characterisation of Cryptococcus species from living
      trees in Havana city, Cuba.
AB  - Cryptococcus isolates from Cuban patients were identified as C. neoformans var.
      grubii. Although this species has since long been associated with bird droppings,
      a recent genotyping study provided strong evidence for additional origins of
      exposure. We sampled different species of trees in Havana, Cuba to identify other
      potential sources of exposure to this fungus. A total of 662 samples were
      collected from 331 trees and cacti from Havana, Cuba. Initial selection of the
      isolates was carried out by conventional techniques. Isolates were further
      characterised using a combination of AFLP analysis and DNA sequence analysis.
      Identification by conventional methods yielded 121 C. neoformans and 61 C. gattii
      isolates. Molecular analyses showed that none of these isolates was C. gattii and
      only one isolate proved to be C. neoformans var. grubii. A total of 27 different
      other species were identified. The most prevalent species was C. heveanensis
      (33%). Sixty-five unidentifiable isolates segregated into ten potentially novel
      species. Conventional cultivation methods have a low specificity for C.
      neoformans complex and molecular analyses need to be applied to confirm
      identification of isolates from environmental sources. Environmental niches
      responsible for most of human cryptococcal infections in Cuba remain to be
      identified.

PMID- 22364257
TI  - Halogen bonding in DNA base pairs.
AB  - Halogen bonding (R-X...Y) is a qualitative analogue of hydrogen bonding that may
      prove useful in the rational design of artificial proteins and nucleotides. We
      explore halogen-bonded DNA base pairs containing modified guanine, cytosine,
      adenine and thymine nucleosides. The structures and stabilities of the
      halogenated systems are compared to the normal hydrogen bonded base pairs. In
      most cases, energetically stable, coplanar structures are identified. In the most
      favorable cases, halogenated base pair stabilities are within 2 kcal mol(-1) of
      the hydrogen bonded analogues. Among the halogens X = Cl, Br, and I, bromine is
      best suited for inclusion in these biological systems because it possesses the
      best combination of polarizability and steric suitability. We find that the most
      stable structures result from a single substitution of a hydrogen bond for a
      halogen bond in dA:dT and dG:dC base pairs, which allows 1 or 2 hydrogen bonds,
      respectively, to complement the halogen bond.

PMID- 22364256
TI  - Putting the brakes on a cycle: bottom-up effects damp cycle amplitude.
AB  - Pest population density oscillations have a profound effect on agroecosystem
      functioning, particularly when pests cycle with epidemic persistence. Here, we
      ask whether landscape-level manipulations can be used to restrict the cycle
      amplitude of the European corn borer moth [Ostrinia nubilalis (Hubner)], an
      economically important maize pest. We analysed time series from Minnesota (1963
      2009) and Wisconsin (1964-2009) to quantify the extent of regime change in the US
      Corn Belt where rates of transgenic Bt maize adoption varied. The introduction of
      Bt maize explained cycle damping when the adoption of the crop was high
      (Minnesota); oscillations were damped but continued to persist when Bt maize was
      used less intensely (Wisconsin). We conclude that host plant quality is key to
      understanding both epidemic persistence and the success of intervention
      strategies. In particular, the dichotomy in maize management between states is
      thought to limit the spatial autocorrelation of O. nubilalis.

PMID- 22364254
TI  - Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of
      Bacopa monnieri and Bacoside-A.
AB  - BACKGROUND: Gamma amino butyric acid (GABA), the principal inhibitory
      neurotransmitter in the cerebral cortex, maintains the inhibitory tones that
      counter balances neuronal excitation. When this balance is perturbed, seizures
      may ensue. METHODS: In the present study, alterations of the general GABA, GABAA
      and GABAB receptors in the cerebral cortex of the epileptic rat and the
      therapeutic application of Bacopa monnieri were investigated. RESULTS: Scatchard
      analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of
      the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to
      control. Real Time PCR amplification of GABA receptor subunits such as
      GABAAalpha1, GABAAgamma, GABAAdelta, GABAB and GAD where down regulated (P <
      0.001) in epileptic rats. GABAAalpha5 subunit and Cyclic AMP responsible element
      binding protein were up regulated. Confocal imaging study confirmed the decreased
      GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y
      maze performance. CONCLUSIONS: Bacopa monnieri and Bacoside-A treatment reverses
      epilepsy associated changes to near control suggesting that decreased GABA
      receptors in the cerebral cortex have an important role in epileptic occurrence;
      Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy
      management.

PMID- 22364258
TI  - MicroRNA-34a regulates the longevity-associated protein SIRT1 in coronary artery
      disease: effect of statins on SIRT1 and microRNA-34a expression.
AB  - Endothelial senescence is thought to play a role in CAD (coronary artery
      disease). miR-34a (microRNA-34a) and other SIRT1 (silent information regulator 1)
      related miRs have recently been found to target SIRT1 leading to endothelial
      senescence. In the present study, we investigated whether SIRT1-related miRs,
      including miR-9, miR-34a, miR-132, miR-181a, miR-195, miR-199a, miR-199b and miR
      204, and SIRT1 were expressed in EPCs (endothelial progenitor cells) obtained
      from patients with CAD, and whether statins (atorvastatin or rosuvastatin)
      affected these levels. To determine the effects of miR-34a on SIRT1, cultured
      EPCs transfected with miR-34a were analysed for total SIRT1 protein levels. EPCs
      were obtained from 70 patients with CAD and 48 subjects without CAD. Patients
      with CAD were randomized to 8 months of treatment with atorvastatin or
      rosuvastatin. EPCs were obtained from peripheral blood at baseline and after 8
      months of statin therapy. Levels of miRs and SIRT1 in EPCs were measured by real
      time RT-PCR (reverse transcription-PCR) and FACS. Functional approaches to miR
      34a have shown that transfection of miR-34a into EPCs resulted in regulation of
      SIRT1 expression. Levels of miR-34a were higher in the CAD group than in the non
      CAD group, whereas levels of SIRT1 protein were lower in the CAD group than in
      the non-CAD group. There were no significant differences in other miRs (miR-9,
      miR-132, miR-181a, miR-195, miR-199a, miR-199b and miR-204) between the two
      groups. Levels of miR-34a were mildly negatively correlated with SIRT1 protein
      levels. A randomized clinical study has shown that the atorvastatin group had
      markedly decreased miR-34a levels and increased SIRT1 levels, whereas the
      rosuvastatin group showed no change in these levels. Levels of other miRs
      remained unchanged in the atorvastatin and rosuvastatin groups. In conclusion the
      results of the present study suggest that miR-34a may regulate SIRT1 expression
      in EPCs and that atorvastatin up-regulates SIRT1 expression via inhibition of miR
      34a, possibly contributing to the beneficial effects of atorvastatin on
      endothelial function in CAD.

PMID- 22364259
TI  - A comparison of two clinical methods for measuring saliva in patients with
      Sjogren's syndrome.
AB  - OBJECTIVE: The aim of the present study was to evaluate two different ways of
      measuring unstimulated and stimulated whole salivary output in the dental clinic,
      namely by volume (mL/min) and by weight (g/min). MATERIALS AND METHODS: Thirty
      one patients diagnosed with Secondary Sjogren's syndrome (SSS) participated in
      the study. RESULTS: The results showed a large discrepancy between the
      measurements performed by volume and by weight (p < 0.001) and additionally when
      taking into account density calculation, especially in individuals with low
      salivary secretion rate. CONCLUSION: It is suggested that weight measurement of
      saliva should be more routinely implemented, especially in patients with reduced
      salivary secretion.

PMID- 22364261
TI  - Newer insights into the drug delivery approaches of alpha-glucosidase inhibitors.
AB  - INTRODUCTION: alpha-Glucosidase inhibitors (AGIs) are an important category of
      oral antidiabetic agents being extensively exploited for the effective management
      of type 2 diabetes and associated disorders. These drugs significantly reduce the
      postprandial rise in glycemic and plasma insulin levels both in nondiabetics and
      in type 2 diabetic patients. Currently only three drugs belonging to this
      category, viz, acarbose, miglitol and voglibose are in the market. The major
      limitations associated with the administration of AGIs are the stringent
      repetitive dosing schedule at specified time intervals, along with a high
      incidence of gastrointestinal disturbances that mainly include flatulence,
      abdominal distension, borborygmus and diarrhea. All these factors tend to
      decrease patient compliance. AREAS COVERED: This review focuses on the various
      formulation approaches being targeted for the effective delivery of AGIs, viz,
      unit matrix systems, bioadhesive pellets, hydrogels and lipid-based granules.
      EXPERT OPINION: It is concluded that development of a successful controlled
      release delivery system for these drugs will obviate the need of repeated
      administration, which in turn will improve patient compliance.

PMID- 22364263
TI  - Ubiquitylation of Drosophila p54/Rpn10/S5a regulates its interaction with the UBA
      UBL polyubiquitin receptors.
AB  - Analysis of the in vivo ubiquitylation of the p54/Rpn10 polyubiquitin receptor
      subunit of the Drosophila 26S proteasome revealed that the site of ubiquitylation
      is the C-terminal cluster of lysines, which is conserved in higher eukaryotes.
      Extraproteasomal p54 was extensively multiubiquitylated, but only very modest
      modification was detected in the proteasome-assembled subunit. Ubiquitylation of
      p54 seriously jeopardizes one of its most important functions, i.e., the
      interaction of its ubiquitin-interacting motifs with the ubiquitin-like domain of
      Dsk2 and Rad23 extraproteasomal polyubiquitin receptors. This modification of p54
      supports the previous notion that p54 is a shuttling subunit of the 26S
      proteasome with a specific extraproteasomal function. This assumption is
      supported by the observation that, while transgenic p54 can fully rescue the
      lethal phenotype of the Deltap54 null mutation, its derivative from which the
      cluster of conserved lysines is deleted shifts the lethality from the early pupa
      to pharate adult stage but cannot rescue the Deltap54 mutation, suggesting that
      ubiquitylated extraproteasomal p54 has an essential role in the pupa-adult
      transition.

PMID- 22364262
TI  - Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated
      alcoholic liver fibrosis - a randomized open-label controlled study.
AB  - BACKGROUND: Recent studies have shown that the renin-angiotensin system is
      implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was
      done in humans with alcoholic liver disease. AIM: To investigate the antifibrotic
      effect of angiotensin II type 1 receptor (AT1-R) blocking agents (ARB) in
      patients with alcoholic liver disease. METHODS: The primary outcome was
      improvement in patients' histological features. Eighty-five patients with
      compensated alcoholic liver fibrosis (>= F2) which was confirmed by baseline
      liver biopsy were randomized (intention-to-treat (ITT)) to receive either ARB,
      candesartan (8 mg/day) with ursodeoxycholic acid (UDCA) (600 mg/day) (n = 42) or
      UDCA alone (n = 43) as control for 6 months and follow-up liver biopsies were
      conducted. RESULTS: According to the Laennec fibrosis system, candesartan showed
      significantly higher rates of histological improvements (ITT, 33.3% vs. 11.6%, P
      = 0.020). In addition, the fibrosis score was significantly reduced from 3.4 +/-
      1.4 to 3.1 +/- 1.5 (P = 0.005) in the candesartan group. Candesartan also reduced
      the area of fibrosis and alpha-smooth muscle actin positive from 11.3 +/- 6.0 to
      8.3 +/- 4.7 and 28.7 +/- 10.5 to 23.9 +/- 10.3 (%), and the hydroxyproline levels
      (MUg/g liver tissue) from 7.8 +/- 2.4 to 6.3 +/- 1.7 respectively (P < 0.05). In
      addition, the relative expression of transforming growth factor-beta1(TGF-beta1),
      collagen-1, AT1-R, tissue inhibitor of metalloproteinase 1 (TIMP-1),
      metalloproteinases2 (MMP2), Rac1 and p22phox by real-time RT-PCR decreased in the
      candesartan group (P < 0.05). Mean arterial blood pressure in the candesartan
      group decreased mildly but significantly (P < 0.001). No significant
      complications and side effects were observed during the present study.
      CONCLUSIONS: Administration of ARB in compensated alcoholic liver disease induces
      improvement of fibrosis in histological and quantitative measurements.

PMID- 22364264
TI  - How girls and boys expect disclosure about problems will make them feel:
      implications for friendships.
AB  - Although girls disclose to friends about problems more than boys, little is known
      about processes underlying this sex difference. Four studies (Ns = 526, 567, 769,
      154) tested whether middle childhood to mid-adolescent girls and boys (ranging
      from 8 to 17 years old) differ in how they expect that talking about problems
      would make them feel. Girls endorsed positive expectations (e.g., expecting to
      feel cared for, understood) more strongly than boys. Despite common perceptions,
      boys did not endorse negative expectations such as feeling embarrassed or worried
      about being made fun of more than girls. Instead, boys were more likely than
      girls to expect to feel "weird" and like they were wasting time. Sex differences
      in outcome expectations did help to account for girls' greater disclosure to
      friends.

PMID- 22364265
TI  - Detection of the early stage of recombinational DNA repair by silicon nanowire
      transistors.
AB  - A silicon nanowire-based biosensor has been designed and applied for label-free
      and ultrasensitive detection of the early stage of recombinational DNA repair by
      RecA protein. Silicon nanowires transistors were fabricated by atomic force
      microscopy nanolithography and integrated into a microfluidic environment. The
      sensor operates by measuring the changes in the resistance of the nanowire as the
      biomolecular reactions proceed. We show that the nanoelectronic sensor can detect
      and differentiate several steps in the binding of RecA to a single-stranded DNA
      filament taking place on the nanowire-aqueous interface. We report relative
      changes in the resistance of 3.5% which are related to the interaction of 250
      RecA.single-stranded DNA complexes. Spectroscopy data confirm the presence of the
      protein-DNA complexes on the functionalized silicon surfaces.

PMID- 22364266
TI  - Light might directly affect retinal ganglion cell mitochondria to potentially
      influence function.
AB  - Visible light (360-760 nm) entering the eye impinges on the many ganglion cell
      mitochondria in the non-myelinated part of their axons. The same light also
      disrupts isolated mitochondrial function in vitro and kills cells in culture with
      the blue light component being particularly lethal whereas red light has little
      effect. Significantly, a defined light insult only affects the survival of
      fibroblasts in vitro that contain functional mitochondria supporting the view
      that mitochondrial photosensitizers are influenced by light. Moreover, a blue
      light insult to cells in culture causes a change in mitochondrial structure and
      membrane potential and results in a release of cytochrome c. Blue light also
      causes an alteration in mitochondria located components of the OXPHOS (oxidative
      phosphorylation system). Complexes III and IV as well as complex V are
      significantly upregulated whereas complexes I and II are slightly but
      significantly up- and downregulated, respectively. Also, blue light causes
      Dexras1 and reactive oxygen species to be upregulated and for mitochondrial
      located apoptosis-inducing factor to be activated. A blue light detrimental
      insult to cells in culture does not involve the activation of caspases but is
      known to be attenuated by necrostatin-1, typical of a death mechanism named
      necroptosis.

PMID- 22364267
TI  - Sol-gel synthesis and characterization of silica polyamine composites:
      applications to metal ion capture.
AB  - A sol-gel method has been developed for the synthesis of composite materials
      analogous to the previously reported and commercialized silica polyamine
      composite (SPC) materials made from amorphous silica. Monolithic xerogels were
      formed using a two-step procedure with no templating agent using acid catalyzed
      followed by base catalyzed hydrolysis. This reaction was followed by (1)H NMR.
      Initial sol-gels were formed using a methyltrimethoxysilane (MTMOS) and 3
      chloropropyltrimethoxysilane (CPTMOS) mixture. Elemental analyses and (13)C CPMAS
      NMR confirmed incorporation of both monomeric units into the surface structure.
      Some control over surface morphology was achieved by adjusting synthetic
      conditions. The resulting xerogels were reacted with poly(allylamine) (PAA) to
      give composite materials which showed much lower metal ion capacities than the
      commercially available amorphous silica analogs. The low degree of reaction of
      the chloropropyl groups indicated they were not surface-available to the
      polyamine. Addition of tetramethoxysilane (TMOS) produced a structural matrix and
      resulted in higher chloride utilization (reaction of surface chloropropyl groups
      with the polyamine). The ratio of the three siloxane monomeric components was
      varied until the resulting polyamine composite xerogels had metal capacities
      comparable with the commercialized SPC materials. These composites had narrower
      average pore size distributions and fewer small pores. Further modification of
      these composites with metal selective ligands showed material characteristics
      similar to those of commercially available SPC materials. Subjecting a composite
      made by the sol-gel route to one thousand load-strip cycles with Cu(2+) shows
      essentially no loss in metal capacity, and this robustness compares favorably
      with that observed for the SPC made from amorphous silica gels.

PMID- 22364268
TI  - Strain-engineering of band gaps in piezoelectric boron nitride nanoribbons.
AB  - Two-dimensional atomic sheets such as graphene and boron nitride monolayers
      represent a new class of nanostructured materials for a variety of applications.
      However, the intrinsic electronic structure of graphene and h-BN atomic sheets
      limits their direct application in electronic devices. By first-principles
      density functional theory calculations we demonstrate that band gap of zigzag BN
      nanoribbons can be significantly tuned under uniaxial tensile strain. The
      unexpected sensitivity of band gap results from reduced orbital hybridization
      upon elastic strain. Furthermore, sizable dipole moment and piezoelectric effect
      are found in these ribbons owing to structural asymmetry and hydrogen
      passivation. This will offer new opportunities to optimize two-dimensional
      nanoribbons for applications such as electronic, piezoelectric, photovoltaic, and
      opto-electronic devices.

PMID- 22364270
TI  - TEAhM-Technologies for Enhancing Access to Health Management: a pilot study of
      community-based telehealth.
AB  - OBJECTIVE: To explore implementation of nurse-mediated telehealth in community
      based senior centers. MATERIALS AND METHODS: Two senior centers had telehealth
      kiosks installed, and two other centers served as control sites. Participants
      with diagnosed hypertension were instructed to use the equipment at least once
      per week to measure blood pressure (BP). Nurses monitored BP data for 10 months
      and made referrals based on primary care physicians' protocols. RESULTS:
      Participants' mean age was 74.1 years, 75% were women, and mean baseline systolic
      BPs were 131 and 138 mm Hg in the intervention and control groups, respectively.
      At baseline, 64% and 85% of participants reported ever having owned a home
      computer and cell phone, respectively, and 84% reported having used an automated
      BP device outside of a doctor's office. At 10 months, mean systolic BP was 126
      and 132 mm Hg in the intervention and control groups, respectively. Intervention
      participants used the telehealth station once per week during 69% of all follow
      up weeks, and 71% of high readings received nurse follow-up within 24 h. Kiosk
      use increased steadily during the follow-up period, peaking at 80%, but declined
      over time to 47% at 10 months. Nearly all intervention group participants
      reported being "very comfortable" with the technology at study end, 81% reported
      it was "very easy" to use, and 89% would recommend it to friends. Senior center
      staff reported that the technology was consistent with their organizational
      mission and that clients and boards of directors were enthusiastic about it.
      CONCLUSIONS: This pilot study demonstrates that telehealth was embraced by
      clients and staff of community-based senior centers. A larger study is needed to
      determine the clinical impact and cost-effectiveness of using senior centers as a
      venue for telehealth-based management of hypertension and other common chronic
      conditions.

PMID- 22364272
TI  - Combined effect of anterior malocclusion and inadequate lip coverage on dental
      trauma in primary teeth.
AB  - OBJECTIVES:   The main objective of this study was to investigate whether the
      interaction of malocclusion (open bite or increased overjet) combined with
      inadequate lip coverage strengthens its association with traumatic dental injury
      (TDI) in the primary teeth of preschool children compared to the presence of
      malocclusion alone. SUBJECTS AND METHODS:   A cross-sectional survey was
      conducted with 376 children aged 36-59 months who attended the National Day of
      Children's Vaccination. Presence of TDI, tooth discoloration, and sinus tract
      were evaluated in the children. Variables associated with occlusion were also
      evaluated. A Poisson regression analysis was performed to verify the association
      between the explanatory variables and TDI as well as possible interactions among
      the variables. Then, the prevalence ratio was calculated. RESULTS:   The
      prevalence of TDI was 27.7%. The maxillary central incisor was the most affected
      tooth, without differences between the right and left sides. Boys had more dental
      trauma than girls (P = 0.04). The most common TDI was crown fracture restricted
      to the enamel (58.4%). Children with a combination of anterior open bite or
      increased overjet and inadequate lip coverage presented a higher prevalence of
      TDI than when the malocclusions were presented alone (P < 0.05). The same trends
      were observed when we included, in the final adjusted model, increased overjet
      instead of open bite. CONCLUSIONS:   Anterior malocclusions of primary teeth such
      as increased overjet and anterior open bite are statistically significantly
      associated with dental trauma only when inadequate lip coverage is also present.

PMID- 22364271
TI  - Parasitic wasp responses to symbiont-based defense in aphids.
AB  - BACKGROUND: Recent findings indicate that several insect lineages receive
      protection against particular natural enemies through infection with heritable
      symbionts, but little is yet known about whether enemies are able to discriminate
      and respond to symbiont-based defense. The pea aphid, Acyrthosiphon pisum,
      receives protection against the parasitic wasp, Aphidius ervi, when infected with
      the bacterial symbiont Hamiltonella defensa and its associated bacteriophage APSE
      (Acyrthosiphon pisum secondary endosymbiont). Internally developing parasitoid
      wasps, such as A. ervi, use maternal and embryonic factors to create an
      environment suitable for developing wasps. If more than one parasitoid egg is
      deposited into a single aphid host (superparasitism), then additional complements
      of these factors may contribute to the successful development of the single
      parasitoid that emerges. RESULTS: We performed experiments to determine if
      superparasitism is a tactic allowing wasps to overcome symbiont-mediated defense.
      We found that the deposition of two eggs into symbiont-protected aphids
      significantly increased rates of successful parasitism relative to singly
      parasitized aphids. We then conducted behavioral assays to determine whether A.
      ervi selectively superparasitizes H. defensa-infected aphids. In choice tests, we
      found that A. ervi tends to deposit a single egg in uninfected aphids, but two or
      more eggs in H. defensa-infected aphids, indicating that oviposition choices may
      be largely determined by infection status. Finally, we identified differences in
      the quantity of the trans-beta-farnesene, the major component of aphid alarm
      pheromone, between H. defensa-infected and uninfected aphids, which may form the
      basis for discrimination. CONCLUSIONS: Here we show that the parasitic wasp A.
      ervi discriminates among symbiont-infected and uninfected aphids, and changes its
      oviposition behavior in a way that increases the likelihood of overcoming
      symbiont-based defense. More generally, our results indicate that natural enemies
      are not passive victims of defensive symbionts, and that an evolutionary arms
      race between A. pisum and the parasitoid A. ervi may be mediated by a bacterial
      symbiosis.

PMID- 22364273
TI  - Phylogenetic distribution of genes encoding beta-glucuronidase activity in human
      colonic bacteria and the impact of diet on faecal glycosidase activities.
AB  - Bacterial beta-glucuronidase in the human colon plays an important role in
      cleaving liver conjugates of dietary compounds and xenobiotics, while other
      glycosidase activities are involved in the conversion of dietary plant
      glycosides. Here we detected an increase in beta-glucuronidase activity in faecal
      samples from obese volunteers following a high-protein moderate carbohydrate
      weight-loss diet, compared with a weight maintenance diet, but little or no
      changes were observed when the type of fermentable carbohydrate was varied. Other
      faecal glycosidase activities showed little or no change over a fivefold range of
      dietary NSP intake, although alpha-glucosidase increased on a resistant starch
      enriched diet. Two distinct groups of gene, gus and BG, have been reported to
      encode beta-glucuronidase activity among human colonic bacteria. Degenerate
      primers were designed against these genes. Overall, Firmicutes were found to
      account for 96% of amplified gus sequences, with three operational taxonomic
      units particularly abundant, whereas 59% of amplified BG sequences belonged to
      Bacteroidetes and 41% to Firmicutes. A similar distribution of operational
      taxonomic units was found in a published metagenome dataset involving a larger
      number of volunteers. Seven cultured isolates of human colonic bacteria that
      carried only the BG gene gave relatively low beta-glucuronidase activity that was
      not induced by 4-nitrophenyl-beta-D-glucuronide. By comparison, in three of five
      isolates that possessed only the gus gene, beta-glucuronidase activity was
      induced.

PMID- 22364274
TI  - The role of motor experience in understanding action function: the case of the
      precision grasp.
AB  - Recent evidence suggests adults and infants selectively attend to features of
      action, such as how a hand contacts an object. The current research investigated
      whether this bias stems from infants' processing of the functional consequences
      of grasps: understanding that different grasps afford different future actions. A
      habituation paradigm assessed 10-month-old infants' (N = 62) understanding of the
      functional consequences of precision and whole-hand grasps in others' actions,
      and infants' own precision grasping abilities were also assessed. The results
      indicate infants understood the functional consequences of another's grasp only
      if they could perform precision grasps themselves. These results highlight a
      previously unknown aspect of early action understanding, and deepen our
      understanding of the relation between motor experience and cognition.

PMID- 22364275
TI  - Gastric neuromodulation with Enterra system for nausea and vomiting in patients
      with gastroparesis.
AB  - OBJECTIVE: Gastric electrical stimulation (GES) has been introduced for treating
      gastric motility disorders, such as gastroparesis, and obesity. A special method
      of GES using high frequency-short pulses, called Enterra(r) Therapy, has been
      clinically applied to treat nausea and vomiting in patients with gastroparesis.
      However, its mechanisms are not well understood. MATERIALS AND METHODS: General
      methodologies of GES published in the literature are systematically reviewed and
      their main effects and application are presented. The major part of this review
      is focused on Enterra Therapy since this is the only method that has been used
      clinically. A number of different GES methods have been proposed. RESULTS: GES
      with long pulses or dual pulses, but not short pulses, are able to alter (enhance
      or inhibit) such parameters of gastric motility as gastric slow waves and gastric
      emptying. Synchronized GES has been reported to improve antral contractions. GES
      with high frequency-short pulses, or Enterra Therapy, is known to improve nausea
      and vomiting in patients with gastroparesis and has a response rate of 50-70%.
      Improved gastric accommodation, direct enteric nervous system effects, enhanced
      vagal activity, and activation of central neurons are believed to be the
      underlying mechanisms involved in the antiemetic effect of this therapy.
      CONCLUSIONS: GES with high frequency-short pulses effectively reduces nausea and
      vomiting in patients with gastroparesis. This antiemetic effect could be mediated
      via enteric, autonomic, and/or central neural mechanisms. Further systematic and
      controlled studies are needed to improve the efficacy of Enterra Therapy and to
      understand its mechanisms of action.

PMID- 22364276
TI  - Short-term outcome in living donors for lung transplantation: the role of
      preoperative computer tomographic evaluations of fissures and vascular anatomy.
AB  - Successful living-donor lobar lung transplantation (LDLLT) largely depends on
      donor outcome. We reviewed our experiences with LDLLT and focused on preoperative
      computed tomographic evaluations of donors. Twenty-five LDLLTs were performed in
      Kyoto University. As a routine preoperative assessment, high-resolution chest
      computed tomography (CT), and three-dimensional (3D)-CT angiography were
      performed. Preoperative evaluations, surgical procedures, and early postoperative
      outcomes were reviewed in 43 consecutive LDLLT donors. All donors were discharged
      home after the donor lobectomies. Severely incomplete fissures were
      intraoperatively identified in two donors, whose interlobar fissures were mostly
      not identified by high resolution CT preoperatively. Preoperative 3D-CT
      angiography was effective for the identification of the branches of the pulmonary
      artery and vein. Pulmonary arterioplasties were performed with auto pericardial
      patches in three left donors. The bilateral donors had to be exchanged because of
      an anomaly of the pulmonary veins in one donor. Small pulmonary arterial branches
      to the remaining lobes were to be sacrificed in 23 donors (53%). Early
      postoperative complications were ascertained in seven donors, and five of them
      presented air leak-related complications. Living donor lobectomies were safely
      performed with low morbidities in our institution. Preoperative computer
      tomographic evaluations might be useful in donor lobectomies.

PMID- 22364277
TI  - Novel GSK-3beta inhibitors and CBM-1078 guide hATSCs' deaging via Oct4 and beta
      catenin activation.
AB  - Abstract Aims: The fate decision of adult stem cells is determined by the
      activation of specific intracellular signaling pathways after exposure to
      specific stimuli. In this study, we demonstrated specific functions of a novel
      small molecule, CBM-1078, that induced cell self-renewal via Oct4- and canonical
      Wnt/beta-catenin-mediated deaging in cultured human adipose tissue-derived stem
      cells (hATSCs). RESULTS: As a potential glycogen synthase kinase-3beta (GSK
      3beta) inhibitor, CBM-1078 primarily activated beta-catenin and Oct4 expression
      after inhibition of GSK-3beta. Treatment of hATSCs with CBM-1078 led to
      transdifferentiation toward a neural precursor cell fate after transient self
      renewal, and the cells were capable of differentiation into gamma-Aminobutyric
      acid (GABA)-secreting neuronal cells with pain-modulating functions in an animal
      model of neuropathic pain. During cell self-renewal, CBM-1078 directs the
      translocalization of beta-catenin and Oct4 into the nucleus, an event that is
      crucial for the cooperative activation of hATSC neurogenesis via Oct4 and
      Wnt/beta-catenin. Nuclear-localized beta-catenin and Oct4 act together to
      regulate the expression of Oct4, Nanog, Sox2, beta-catenin, c-Myc, and STAT3
      after binding to the regulatory regions of these genes. Nuclear Oct4 and
      Wnt3a/beta-catenin also control cell growth by binding to the promoters of STAT3,
      Gli3, and c-Myc after complex formation and direct interaction. CBM-1078 actively
      enhanced the DNA-binding affinity of Oct4 and beta-catenin to functional genes
      and activated the Wnt/beta-catenin pathway to promote hATSC reprogramming.
      INNOVATION AND CONCLUSION: This study revealed the value of a single small
      molecule, CBM-1078, showing a definitive cell reprogramming mechanism. Finally,
      we confirmed the therapeutic potential of GABA-hATSCs for treatment of
      neuropathic pain, which could be used for therapeutic purposes in humans.
      Antioxid. Redox Signal. 00, 000-000.

PMID- 22364279
TI  - Large-scale integration of semiconductor nanowires for high-performance flexible
      electronics.
AB  - High-performance flexible electronics has attracted much attention in recent
      years due to potential applications in flexible displays, artificial skin, radio
      frequency identification, sensor tapes, etc. Various materials such as organic
      and inorganic semiconductor nanowires, carbon nanotubes, graphene, etc. have been
      explored as the active semiconductor components for flexible devices. Among them,
      inorganic semiconductor nanowires are considered as highly promising materials
      due to their relatively high carrier mobility, reliable control on geometry and
      electronic properties, and cost-effective synthesis processes. In this review,
      recent progress on the assembly of high-performance inorganic semiconductor
      nanowires and their applications for large-scale flexible electronics will be
      summarized. In particular, nanowire-based integrated circuitry and high-frequency
      electronics will be highlighted.

PMID- 22364282
TI  - Targeting Lyn tyrosine kinase through protein fusions encompassing motifs of Cbp
      (Csk-binding protein) and the SOCS box of SOCS1.
AB  - The tyrosine kinase Lyn is involved in oncogenic signalling in several leukaemias
      and solid tumours, and we have previously identified a pathway centred on Cbp
      [Csk (C-terminal Src kinase)-binding protein] that mediates both enzymatic
      inactivation, as well as proteasomal degradation of Lyn via phosphorylation
      dependent recruitment of Csk (responsible for phosphorylating the inhibitory C
      terminal tyrosine of Lyn) and SOCS1 (suppressor of cytokine signalling 1; an E3
      ubiquitin ligase). In the present study we show that fusing specific functional
      motifs of Cbp and domains of SOCS1 together generates a novel molecule capable of
      directing the proteasomal degradation of Lyn. We have characterized the binding
      of pY (phospho-tyrosine) motifs of Cbp to SFK (Src-family kinase) SH2 (Src
      homology 2) domains, identifying those with high affinity and specificity for the
      SH2 domain of Lyn and that are preferred substrates of active Lyn. We then fused
      them to the SB (SOCS box) of SOCS1 to facilitate interaction with the
      ubiquitination-promoting elongin B/C complex. As an eGFP (enhanced green
      fluorescent protein) fusion, these proteins can direct the polyubiquitination and
      proteasomal degradation of active Lyn. Expressing this fusion protein in DU145
      cancer cells (but not LNCaP or MCF-7 cells), that require Lyn signalling for
      survival, promotes loss of Lyn, loss of caspase 3, appearance of an apoptotic
      morphology and failure to survive/expand. These findings show how functional
      domains of Cbp and SOCS1 can be fused together to generate molecules capable of
      inhibiting the growth of cancer cells that express high levels of active Lyn.

PMID- 22364283
TI  - IkappaB kinase beta (IKKbeta) does not mediate feedback inhibition of the insulin
      signalling cascade.
AB  - In the present study, we have examined whether IKKbeta [IkappaB (inhibitor of
      nuclear factor kappaB) kinase beta] plays a role in feedback inhibition of the
      insulin signalling cascade. Insulin induces the phosphorylation of IKKbeta, in
      vitro and in vivo, and this effect is dependent on intact signalling via PI3K
      (phosphoinositide 3-kinase), but not PKB (protein kinase B). To test the
      hypothesis that insulin activates IKKbeta as a means of negative feedback, we
      employed a variety of experimental approaches. First, pharmacological inhibition
      of IKKbeta via BMS-345541 did not potentiate insulin-induced IRS1 (insulin
      receptor substrate 1) tyrosine phosphorylation, PKB phosphorylation or 2
      deoxyglucose uptake in differentiated 3T3-L1 adipocytes. BMS-345541 did not
      prevent insulin-induced IRS1 serine phosphorylation on known IKKbeta target
      sites. Secondly, adenovirus-mediated overexpression of wild-type IKKbeta in
      differentiated 3T3-L1 adipocytes did not suppress insulin-stimulated 2
      deoxyglucose uptake, IRS1 tyrosine phosphorylation, IRS1 association with the p85
      regulatory subunit of PI3K or PKB phosphorylation. Thirdly, insulin signalling
      was not potentiated in mouse embryonic fibroblasts lacking IKKbeta. Finally,
      insulin treatment of 3T3-L1 adipocytes did not promote the recruitment of IKKbeta
      to IRS1, supporting our findings that IKKbeta, although activated by insulin,
      does not promote direct serine phosphorylation of IRS1 and does not contribute to
      the feedback inhibition of the insulin signalling cascade.

PMID- 22364281
TI  - PI3K signalling in B- and T-lymphocytes: new developments and therapeutic
      advances.
AB  - Activation of PI3K (phosphoinositide 3-kinase) is a shared response to engagement
      of diverse types of transmembrane receptors. Depending on the cell type and
      stimulus, PI3K activation can promote different fates including proliferation,
      survival, migration and differentiation. The diverse roles of PI3K signalling are
      well illustrated by studies of lymphocytes, the cells that mediate adaptive
      immunity. Genetic and pharmacological experiments have shown that PI3K activation
      regulates many steps in the development, activation and differentiation of both B
      and T-cells. These findings have prompted the development of PI3K inhibitors for
      the treatment of autoimmunity and inflammatory diseases. PI3K activation,
      however, has both positive and negative roles in immune system activation.
      Consequently, although PI3K suppression can attenuate immune responses it can
      also enhance inflammation, disrupt peripheral tolerance and promote autoimmunity.
      An exciting discovery is that a selective inhibitor of the p110delta catalytic
      isoform of PI3K, CAL-101, achieves impressive clinical efficacy in certain B-cell
      malignancies. A model is emerging in which p110delta inhibition disrupts signals
      from the lymphoid microenvironment, leading to release of leukaemia and lymphoma
      cells from their protective niche. These encouraging findings have given further
      momentum to PI3K drug development efforts in both cancer and immune diseases.

PMID- 22364284
TI  - Elicitation of health state utilities in neuroendocrine tumours.
AB  - BACKGROUND: Neuroendocrine tumours (NETs) are a rare form of neoplasm that can
      arise in most organs of the body and which share many common pathologic features.
      Although curative surgery can be conducted for patients with localised disease,
      once progression occurs and the disease becomes metastatic or un-resectable,
      treatment aims to extend life and maintain quality-of-life for as long as
      possible. The aim of the study was to elicit utilities for health state vignettes
      describing the burdens associated with receiving therapy for advanced NETs.
      METHODS: Health state vignettes were developed by reviewing published literature
      and conducting in-depth interviews with patients and clinical experts. These
      states described the burden associated with both stable and progressive disease,
      in addition to the experience of a number of serious toxicities commonly
      associated with treatments (grade III/IV diarrhoea, hand-foot syndrome,
      hyperglycaemia, nausea/vomiting, pneumonitis, rash, stomatitis, and
      thrombocytopenia). One hundred members of the UK general public valued the states
      using the time trade-off methodology to determine utility values. RESULTS: Stable
      disease had a utility value of 0.77 whilst disease progression was associated
      with a significant decline in health-related quality-of-life (HRQoL) and a value
      of 0.61. Toxicities experienced in the context of stable disease exhibited
      varying degrees of impact, with several being deemed as debilitating as disease
      progression (such as hand-foot syndrome [0.58] and stomatitis [0.56]).
      CONCLUSION: Although vignette studies have been criticised for the difficulty in
      establishing their validity, the collection of health utilities in rare
      populations is challenging. The findings from this study suggest that advanced
      NETs is associated with a considerable HRQoL burden, both as a direct result of
      the disease and the potential of experiencing a number of severe adverse events.
      These values could assist in future economic evaluation processes.

PMID- 22364280
TI  - Cell signalling by reactive lipid species: new concepts and molecular mechanisms.
AB  - The process of lipid peroxidation is widespread in biology and is mediated
      through both enzymatic and non-enzymatic pathways. A significant proportion of
      the oxidized lipid products are electrophilic in nature, the RLS (reactive lipid
      species), and react with cellular nucleophiles such as the amino acids cysteine,
      lysine and histidine. Cell signalling by electrophiles appears to be limited to
      the modification of cysteine residues in proteins, whereas non-specific toxic
      effects involve modification of other nucleophiles. RLS have been found to
      participate in several physiological pathways including resolution of
      inflammation, cell death and induction of cellular antioxidants through the
      modification of specific signalling proteins. The covalent modification of
      proteins endows some unique features to this signalling mechanism which we have
      termed the 'covalent advantage'. For example, covalent modification of signalling
      proteins allows for the accumulation of a signal over time. The activation of
      cell signalling pathways by electrophiles is hierarchical and depends on a
      complex interaction of factors such as the intrinsic chemical reactivity of the
      electrophile, the intracellular domain to which it is exposed and steric factors.
      This introduces the concept of electrophilic signalling domains in which the
      production of the lipid electrophile is in close proximity to the thiol
      containing signalling protein. In addition, we propose that the role of
      glutathione and associated enzymes is to insulate the signalling domain from
      uncontrolled electrophilic stress. The persistence of the signal is in turn
      regulated by the proteasomal pathway which may itself be subject to redox
      regulation by RLS. Cell death mediated by RLS is associated with bioenergetic
      dysfunction, and the damaged proteins are probably removed by the lysosome
      autophagy pathway.

PMID- 22364285
TI  - Budget-impact model for colonoscopy cost calculation and comparison between 2
      litre PEG+ASC and sodium picosulphate with magnesium citrate or sodium phosphate
      oral bowel cleansing agents.
AB  - OBJECTIVE: With the availability of several bowel cleansing agents, physicians
      and hospitals performing colonoscopies will often base their choice of cleansing
      agent purely on acquisition cost. Therefore, an easy to use budget impact model
      has been developed and established as a tool to compare total colon preparation
      costs between different established bowel cleansing agents. METHODS: The model
      was programmed in Excel and designed as a questionnaire evaluating information on
      treatment costs for a range of established bowel cleansing products. The sum of
      costs is based on National Health Service reference costs for bowel cleansing
      products. Estimations are made for savings achievable when using a 2-litre
      polyethylene glycol with ascorbate components solution (PEG+ASC) in place of
      other bowel cleansing solutions. Test data were entered into the model to confirm
      validity and sensitivity. The model was then applied to a set of audit cost data
      from a major hospital colonoscopy unit in the UK. RESULTS: Descriptive analysis
      of the test data showed that the main cost drivers in the colonoscopy process are
      the procedure costs and costs for bed days rather than drug acquisition costs,
      irrespective of the cleansing agent. Audit data from a colonoscopy unit in the UK
      confirmed the finding with a saving of L107,000 per year in favour of PEG+ASC
      when compared to sodium picosulphate with magnesium citrate solution
      (NaPic+MgCit). For every patient group the model calculated overall cost savings.
      This was irrespective of the higher drug expenditure associated with the use of
      PEG+ASC for bowel preparation. Savings were mainly realized through reduced costs
      for repeat colonoscopy procedures and associated costs, such as inpatient length
      of stay. CONCLUSIONS: The budget impact model demonstrated that the primary cost
      driver was the procedure cost for colonoscopy. Savings can be realized through
      the use of PEG+ASC despite higher drug acquisition costs relative to the
      comparator products. From a global hospital funding perspective, the acquisition
      costs of bowel preparations should not be used as the primary reason to select
      the preferred treatment agent, but should be part of the consideration, with an
      emphasis on the clinical outcome.

PMID- 22364286
TI  - Cost-effectiveness of tapentadol prolonged release compared with oxycodone
      controlled release in the UK in patients with severe non-malignant chronic pain
      who failed 1st line treatment with morphine.
AB  - OBJECTIVES: The aim of this analysis was to assess the cost-effectiveness of
      tapentadol PR (prolonged release) compared with oxycodone CR (controlled release)
      in severe non-malignant chronic pain patients in whom controlled release morphine
      was ineffective or not tolerated. METHODS: A Markov model was developed to assess
      costs and benefits over a 1-year time horizon from the National Health Service
      perspective in the UK. Patients could either continue on 2nd line therapy or
      switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients
      failing also 3rd line therapy entered the final absorbing health state (4th
      line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone
      were obtained from the three comparative phase III clinical trials. Costs of
      resource consumption associated with opioid treatment were derived from a
      retrospective database analysis of anonymized patient records. RESULTS: The model
      results predicted that initiating 2nd line therapy with tapentadol leads to
      higher effectiveness and lower costs vs oxycodone. For the overall population
      included in the clinical trials, mean annual costs per patient when treated with
      tapentadol and oxycodone were L3543 and L3656, respectively. Treatment with
      tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237
      quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively),
      meaning that tapentadol dominated oxycodone. For the sub-group of opioid
      experienced patients with severe pain at baseline the ranking in terms of costs
      and QALYs remained unchanged. Extensive sensitivity analyses showed that
      conclusions about the cost-effectiveness are consistent. CONCLUSIONS: The cost
      effectiveness study suggested that initiating 2nd line treatment in patients with
      severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone
      improves patients' quality-of-life and is less costly. Key limitations when
      interpreting the results are the use of different sources to populate the model
      and restricted generalizability due to data extrapolation.

PMID- 22364287
TI  - Genomic scan of selective sweeps in thin and fat tail sheep breeds for
      identifying of candidate regions associated with fat deposition.
AB  - BACKGROUND: Identification of genomic regions that have been targets of selection
      for phenotypic traits is one of the most important and challenging areas of
      research in animal genetics. However, currently there are relatively few genomic
      regions identified that have been subject to positive selection. In this study, a
      genome-wide scan using ~50,000 Single Nucleotide Polymorphisms (SNPs) was
      performed in an attempt to identify genomic regions associated with fat
      deposition in fat-tail breeds. This trait and its modification are very important
      in those countries grazing these breeds. RESULTS: Two independent experiments
      using either Iranian or Ovine HapMap genotyping data contrasted thin and fat tail
      breeds. Population differentiation using FST in Iranian thin and fat tail breeds
      revealed seven genomic regions. Almost all of these regions overlapped with QTLs
      that had previously been identified as affecting fat and carcass yield traits in
      beef and dairy cattle. Study of selection sweep signatures using FST in thin and
      fat tail breeds sampled from the Ovine HapMap project confirmed three of these
      regions located on Chromosomes 5, 7 and X. We found increased homozygosity in
      these regions in favour of fat tail breeds on chromosome 5 and X and in favour of
      thin tail breeds on chromosome 7. CONCLUSIONS: In this study, we were able to
      identify three novel regions associated with fat deposition in thin and fat tail
      sheep breeds. Two of these were associated with an increase of homozygosity in
      the fat tail breeds which would be consistent with selection for mutations
      affecting fat tail size several thousand years after domestication.

PMID- 22364289
TI  - Nitrile imines: matrix isolation, IR spectra, structures, and rearrangement to
      carbodiimides.
AB  - The structures and reactivities of nitrile imines are subjects of continuing
      debate. Several nitrile imines were generated photochemically or thermally and
      investigated by IR spectroscopy in Ar matrices at cryogenic temperatures (Ph-CNN
      H 6, Ph-CNN-CH(3)17, Ph-CNN-SiMe(3)23, Ph-CNN-Ph 29, Ph(3)C-CNN-CPh(3)34, and the
      boryl-CNN-boryl derivative 39). The effect of substituents on the structures and
      IR absorptions of nitrile imines was investigated computationally at the B3LYP/6
      31G* level. IR spectra were analyzed in terms of calculated anharmonic
      vibrational spectra and were generally in very good agreement with the calculated
      spectra. Infrared spectra were found to reflect the structures of nitrile imines
      accurately. Nitrile imines with IR absorptions above 2200 cm(-1) have essentially
      propargylic structures, possessing a CN triple bond (typically PhCNNSiMe(3)23,
      PhCNNPh 29, and boryl-CNN-boryl 39). Nitrile imines with IR absorptions below ca.
      2200 cm(-1) are more likely to be allenic (e.g., HCNNH 1, PhCNNH 6, HCNNPh 43,
      PhCNNCH(3)17, and Ph(3)C-CNN-CPh(3)34). All nitrile imines isomerize to the
      corresponding carbodiimides both thermally and photochemically. Monosubstituted
      carbodiimides isomerize thermally to the corresponding cyanamides (e.g., Ph-N?C?N
      H 5 -> Ph-NH-CN 8), which are therefore the thermal end products for nitrile
      imines of the types RCNNH and HCNNR. This tautomerization is reversible under
      flash vacuum thermolysis conditions.

PMID- 22364288
TI  - Probing the interaction between fluorophores and DNA nucleotides by fluorescence
      correlation spectroscopy and fluorescence quenching.
AB  - We have investigated the association interactions between the fluorescent dyes
      TAMRA, Cy3B and Alexa-546 and the DNA deoxynucleoside monophosphates by means of
      fluorescence quenching and fluorescence correlation spectroscopy (FCS). The
      interactions of Cy3B and TAMRA with the nucleotides produce a decrease in the
      apparent diffusion coefficient of the dyes, which result in a shift toward longer
      times in the FCS autocorrelation decays. Our results with Cy3B demonstrate the
      existence of Cy3B-nucleotide interactions that do not affect the fluorescence
      intensity or lifetime of the dye significantly. The same is true for TAMRA in the
      presence of dAMP, dCMP and dTMP. In contrast, the diffusion coefficient of Alexa
      546 remains practically unchanged even at high concentrations of nucleotide.
      These results demonstrate that interactions between this dye and the four dNMPs
      are not significant. The presence of the negatively charged sulfonates and the
      bulky chlorine atoms in the phenyl group of Alexa 546 possibly prevent strong
      interactions that are otherwise possible for TAMRA. The characterization of dye
      DNA interactions is important in biophysical research because they play an
      important role in the interpretation of energy transfer experiments, and because
      they can potentially affect the structure and dynamics of the DNA.

PMID- 22364290
TI  - Contributions of CF and CF2 Species to fluorocarbon film composition and
      properties for C(x)F(y) plasma-enhanced chemical vapor deposition.
AB  - Inductively-coupled C(x)F(y) (y/x = 2.0-4.0) plasma systems were investigated to
      determine relationships between precursor chemistry, CF(n) radical-surface
      reactivities, and surface properties of deposited films. The contributions of
      CF(n) (n = 1, 2) radicals to film properties were probed via gas-phase
      diagnostics and the imaging of radicals interacting with surfaces (IRIS)
      technique. Time-resolved radical emission data elucidate CF(g) and CF(2)(g)
      production kinetics from the C(x)F(y) source gases and demonstrate that CF(4)
      plasmas inherently lag in efficacy of film formation when compared to C(2)F(6),
      C(3)F(8), and C(3)F(6) systems. IRIS data show that as the precursor y/x ratio
      decreases, the propensity for CF(n) scatter concomitantly declines. Analyses of
      the composition and characteristics of fluorocarbon films deposited on Si wafers
      demonstrate that surface energies of the films decrease markedly with increasing
      film fluorine content. In turn, increased surface energies correspond with
      significant decreases in the observed scatter coefficients for both CF and CF(2).
      These data improve our molecular-level understanding of CF(n) contributions to
      fluorocarbon film deposition, which promises advancements in the ability to
      tailor FC films to specific applications.

PMID- 22364291
TI  - Minor manifestations of periodontal diseases in young adults with type 1 diabetes
      mellitus. Periodontal and microbiological findings.
AB  - OBJECTIVE: The aim of this study was to evaluate periodontal status and
      microbiological conditions in young adults with insulin-dependent diabetes (IDDM)
      in comparison with age- and sex-matched non-diabetic controls. MATERIALS AND
      METHODS: Forty-one patients, 18-24 years of age with IDDM since childhood, were
      examined and the results were compared to those of a group of 41 sex- and age
      matched non-diabetic controls. According to the HbA(1c) %, the group of diabetic
      patients was divided into two groups, with good or poor metabolic control.
      RESULTS: Periodontal health, expressed in probing pocket depths and marginal bone
      loss, was fairly good in all patients. Fifty per cent of the patients in the
      study and control groups displayed probing pocket depths >=4 mm, mostly pocket
      depths 4 mm. These findings were also equally distributed among the patients with
      good and poor metabolic control. No significant differences were found between
      the groups regarding bleeding on probing, but in the number of sites with
      excessive bleeding the study group exhibited higher scores than the healthy
      controls. Different microbiological species were equally distributed between the
      groups. CONCLUSION: Neither periodontal nor microbiological status in young
      adults with IDDM differs from that of healthy controls.

PMID- 22364292
TI  - Quantification system for the viral dynamics of a highly pathogenic simian/human
      immunodeficiency virus based on an in vitro experiment and a mathematical model.
AB  - BACKGROUND: Developing a quantitative understanding of viral kinetics is useful
      for determining the pathogenesis and transmissibility of the virus, predicting
      the course of disease, and evaluating the effects of antiviral therapy. The
      availability of data in clinical, animal, and cell culture studies, however, has
      been quite limited. Many studies of virus infection kinetics have been based
      solely on measures of total or infectious virus count. Here, we introduce a new
      mathematical model which tracks both infectious and total viral load, as well as
      the fraction of infected and uninfected cells within a cell culture, and apply it
      to analyze time-course data of an SHIV infection in vitro. RESULTS: We infected
      HSC-F cells with SHIV-KS661 and measured the concentration of Nef-negative
      (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the
      infectious viral load daily for nine days. The experiments were repeated at four
      different MOIs, and the model was fitted to the full dataset simultaneously. Our
      analysis allowed us to extract an infected cell half-life of 14.1 h, a half-life
      of SHIV-KS661 infectiousness of 17.9 h, a virus burst size of 22.1 thousand RNA
      copies or 0.19 TCID50, and a basic reproductive number of 62.8. Furthermore, we
      calculated that SHIV-KS661 virus-infected cells produce at least 1 infectious
      virion for every 350 virions produced. CONCLUSIONS: Our method, combining in
      vitro experiments and a mathematical model, provides detailed quantitative
      insights into the kinetics of the SHIV infection which could be used to
      significantly improve the understanding of SHIV and HIV-1 pathogenesis. The
      method could also be applied to other viral infections and used to improve the in
      vitro determination of the effect and efficacy of antiviral compounds.

PMID- 22364294
TI  - Hydrogenated TiO2 nanotube arrays for supercapacitors.
AB  - We report a new and general strategy for improving the capacitive properties of
      TiO(2) materials for supercapacitors, involving the synthesis of hydrogenated
      TiO(2) nanotube arrays (NTAs). The hydrogenated TiO(2) (denoted as H-TiO(2)) were
      obtained by calcination of anodized TiO(2) NTAs in hydrogen atmosphere in a range
      of temperatures between 300 to 600  degrees C. The H-TiO(2) NTAs prepared at 400 
      degrees C yields the largest specific capacitance of 3.24 mF cm(-2) at a scan
      rate of 100 mV s(-1), which is 40 times higher than the capacitance obtained from
      air-annealed TiO(2) NTAs at the same conditions. Importantly, H-TiO(2) NTAs also
      show remarkable rate capability with 68% areal capacitance retained when the scan
      rate increase from 10 to 1000 mV s(-1), as well as outstanding long-term cycling
      stability with only 3.1% reduction of initial specific capacitance after 10,000
      cycles. The prominent electrochemical capacitive properties of H-TiO(2) are
      attributed to the enhanced carrier density and increased density of hydroxyl
      group on TiO(2) surface, as a result of hydrogenation. Furthermore, we
      demonstrate that H-TiO(2) NTAs is a good scaffold to support MnO(2)
      nanoparticles. The capacitor electrodes made by electrochemical deposition of
      MnO(2) nanoparticles on H-TiO(2) NTAs achieve a remarkable specific capacitance
      of 912 F g(-1) at a scan rate of 10 mV s(-1) (based on the mass of MnO(2)). The
      ability to improve the capacitive properties of TiO(2) electrode materials should
      open up new opportunities for high-performance supercapacitors.

PMID- 22364295
TI  - Levosalbutamol  for chronic obstructive pulmonary disease: a treatment
      evaluation.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an inflammatory
      disorder associated with considerable morbidity and mortality. beta2-adrenoceptor
      agonists (beta2-agonists) act by stimulating the beta2-adrenoceptor present on
      smooth muscle and other cells in the airways, resulting in bronchodilatation.
      beta2-agonists play a central role in the treatment of breathlessness in patients
      with COPD. Salbutamol is a chiral drug with (R)- and (S)- isomers. Almost all
      beta2-agonists that are currently used are racemic mixtures of (R)- and (S)
      salbutamol. AREAS COVERED: (R)-salbutamol alone (Xenopex(r), generically known as
      levosalbutamol) is now indicated for the treatment or prevention of bronchospasm
      with reversible obstructive airway disease. This evaluation demonstrates that (R)
      salbutamol provides a beneficial beta2-agonist effect at a cellular level and in
      experimental models of airways disease. Furthermore, we demonstrate that (S)
      salbutamol opposes the desirable effects of (R)-salbutamol and can actually cause
      features of asthma and COPD in vitro and in experimental asthma. EXPERT OPINION:
      Despite this strong body of preclinical experimental evidence, (R)-salbutamol has
      not shown consistent superiority over (S)- or racemic salbutamol in the treatment
      of patients with COPD.

PMID- 22364296
TI  - Silence of p15 expression by RNAi enhances cisplatin resistance in hepatocellular
      carcinoma cells.
AB  - The insensitivity of hepatocellular carcinoma to chemotherapy is associated with
      alternation in tumor cell cycling. This current study was designed to investigate
      the impact of p15 silencing on the sensitivity of Human hepatocellular carcinoma
      HepG2 cells to cisplatin. HepG2/CDDP/1.6 and HepG2/CDDP/2.0 cells were induced by
      culture with increased doses of cisplatin and their sensitivities to cis-Diamine
      dichloroplatinum (CDDP) were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT). The impacts of p15 silencing on the cell
      cycling and P-gp expression were characterized by flow cytometry, RT-PCR and
      Western blot assays, respectively. Knockdown of p15 expression dramatically
      reduced the relative levels of p15 expression and the frequency of phase G1,
      promoting cell cycling. On the other hand, knockdown of p15 expression
      significantly up-regulated the expression of P-glycoprotein (P-gp) in
      HepG2/CDDP/2.0 cells, associated with the increased resistance of HepG2 cells to
      CDDP in vitro. In conclusion, the p15 may be a critical regulator of the
      development of CDDP resistance in HepG2 cells.

PMID- 22364297
TI  - The effect of continuous jejunal interposition on gastrointestinal hormones after
      distal gastrectomy.
AB  - The objective of our study was to determine the effect of continuous jejunal
      interposition on gastrointestinal hormones after distal gastrectomy, and lay a
      foundation for surgical management.Distal subtotal gastrectomy experimental model
      were established on 24 adult Beagle dogs. Digestive tract reconstruction of the
      dogs was randomly divided into continuous jejunal interposition group, Billroth
      II anastomosis group and isolated jejunum interposition group. The content of
      serum gastrin, plasma motilin and cholecystokinin after different digestive tract
      reconstructions was detected and compared by enzyme-linked immunosorbent assay.
      In the dogs which received continuous jejunal interposition, postoperative serum
      gastrin level was significantly lower than before surgery either in fasting or
      postprandial state (all p<0.05). The serum gastrin level of continuous jejunal
      interposition group was significantly higher than the other groups in
      postprandial state (all p<0.05), and was significantly higher than Billroth II 
      type anastomosis group in fasting state (p<0.05). Furthermore, the postoperative
      plasma motilin and cholecystokinin levels were significantly higher than before
      surgery either in fasting or postprandial in dogs received continuous jejunal
      interposition (all p<0.05). The postoperative plasma motilin level of continuous
      jejunal interposition group was significantly higher than the other groups in
      postprandial state (all p<0.05), and was significantly higher than Billroth II 
      type anastomosis group in fasting state (p<0.05). However, the postoperative
      cholecystokinin level of continuous jejunal interposition group was significantly
      lower than the other groups (all p <0.05).Continuous jejunal interposition after
      distal gastrectomy could maintain the postoperative plasma motilin and serum
      gastrin in a relatively high level, while cholecystokinin in a low level.

PMID- 22364298
TI  - Glycogen accumulation in cardiomyocytes and cardiotoxic effects after 3NPA
      treatment.
AB  - Mitochondrial toxin 3-nitropropionic acid (3NPA) is a neurotoxin that inhibits
      the activity of succinate dehydrogenase, a key enzyme of oxidative energy
      production, and characteristically provokes neurodegeneration in the striatum,
      resembling Huntington's disease. 3NPA also affects the activity of glycogen
      sinthase-kinase-3b (GSK-3b), an enzyme implicated in glycogen synthesis and in
      signal transduction. The aim of this study was to evaluate cardiac glycogen
      content and histopathological changes in the hearts of rats after subchronic
      treatment with 3NPA.Female adult Wistar rats were treated daily with 30mg/kg of
      3NPA subcutaneously 8 days. The control group was treated with normal saline for
      8 days. For the comparison of measured parameters between groups we used the
      Student's t-test (p<0.05). The stereological evaluation of glycogen content in
      histological sections of the heart was processed with periodic acid-Schiff (PAS).
      Histochemical procedure showed a significant accumulation of glycogen granules in
      the 3NPA group (0.028mm(3)/mm(3)+/-0.022), whereas the hearts of control animals
      were nearly devoid of glycogen granules (0.002mm(3)/mm(3)+/-0.001). Haematoxylin
      eosin histological staining showed diffuse swelling of cardiomyocytes
      (3NPA=15.989MUm +/-1.649; saline=13.456MUm +/- 0.786), loss of cell cross
      striations, lower myofibril volume fraction (3NPA=0.3922mm(3)/mm3 +/- 0.0230,
      saline=0.4550mm(3)/mm3 +/- 0.0083), and mononuclear infiltration in the
      interstitial tissue, mostly along the blood vessels. Sirius red staining showed
      fibrosis of the heart (3NPA=0.0531mm93)/mm(3)+/-0.0090, saline=0.0135mm(3)/mm3 +/
      0.0051). TUNEL staining showed TUNEL-positive cells in the 3NPA group
      (2.04cells/mm2 +/- 0.92) and almost no TUNEL-positive cells in the saline group
      (0.27cells/mm2 +/- 0.14). This experiment shows that 3NPA-induced
      histopathological changes in the heart are accompanied by a significant
      accumulation of glycogen granules in cardiomyocytes.

PMID- 22364299
TI  - Possible involvement of calcium channels and plasma membrane receptors on
      Staurosporine-induced neurite outgrowth.
AB  - Staurosporine as a protein kinases inhibitor induced cell death or neurite
      outgrowth in PC12 cells. We investigated the involvement of calcium channel and
      plasma membrane receptors on staurosporine inducing neurite outgrowth in PC12
      cells. PC12 cells were preincubated with NMDA receptor inhibitors (1.8 mM
      ketamine and 1uM MK801, treatment 1) or L-Type Calcium channels (100 MUM
      nifedipine and 100 uM flavoxate hydrochloride, treatment 2) or calcium
      calmoduline kinasses (10 MUM trifluoprazine, treatment 3) and nifedipine, MK801,
      flavoxate hydrochloride and ketamine (treatment4) or without pretreatments
      (control). Then, the cells were cultured in RPMI culture medium containing 214nM
      staurosporine for induction of neurite outgrowth. The percentage of Cell
      cytotoxicity and apoptotic index was assessed. Total neurite length (TNL) and
      fraction of cell differentiation were assessed. After 24h, the percentage of cell
      cytotoxicity were increased in treatments 1, 2 and 4 compared with control
      (p<0.05). After 6h, apoptotic index was similar between all treatments. After
      12h, apoptotic index were increased in treatment 4 compared with control
      (p<0.05). After 24h, apoptotic index were increased in treatments 1, 2 and 4
      compared with control (p<0.05). TNL were decreased in treatments 1, 2 and 4
      compared with control in different times of assessment (6, 12 and 24 h) (p<0.05).
      The fraction of cell differentiation were decreased in treatments 1, 2 and 4
      compared with control (p<0.05). It can be concluded that the possible involvement
      of L-type calcium channel and the N-methyl D-aspartate receptor on staurosporine
      induced neurite outgrowth process in PC12 cells.

PMID- 22364300
TI  - Effect of high saturated free fatty acids feeding on progression of renal failure
      in rat model of experimental nephrotoxicity.
AB  - The current study evaluates the impact of high saturated fat feeding in rat model
      of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats
      weighing 200 g were randomized into four groups; the first one received the
      standard rodents chow for 8 weeks and was treated as control, the second group
      (HFD)received an experimental high fat diet rich in palm kernel oil (40% of
      Calories as fat) for the same period. The third group (HFDG) was given 80 mg/kg
      (body weight)/day gentamicin sulphate intraperitoneally during the last 24 days
      of the feeding period while the fourth group was given gentamicin as above along
      with the standard rodents chow. Renal function was assessed through measuring
      serum creatinine, creatinine clearance and absolute and fractional excretion of
      both sodium and potassium. At the end, rats underwent a surgical procedure for
      blood pressure measurement. Renal function study showed a stronger nephrotoxicity
      for HFDG group. Hypertension was observed in HFD group while the pressure
      declined after gentamicin co-administration. Overall, changing the feeding
      behavior toward using more SAFFAs for rats injected with gentamicin promotes the
      progression of renal failure.

PMID- 22364301
TI  - Use of immunochromatographic assay for rapid identification of Mycobacterium
      tuberculosis complex from liquid culture.
AB  - A new, simple immunochromatographic assay for rapid identification of
      Mycobacterium tuberculosis complex in liquid cultures has been developed. The
      principle of the assay is binding of the Mycobacterium tuberculosis complex
      specific antigen to the monoclonal antibody conjugated on the test strip. The aim
      of this study is evaluation of the performance of immunochromatographic assay in
      identification of Mycobacterium tuberculosis complex in primary positive liquid
      cultures of BacT/Alert automated system. A total of 159 primary positive liquid
      cultures were tested using the immunochromatographic assay (BD MGIT TBc ID) and
      the conventional subculture, followed by identification using biochemical
      tests.Of 159 positive liquid cultures, using the conventional method,
      Mycobacterium tuberculosis was identified in 119 (74.8%), nontuberculous
      mycobacteria were found in 4 (2.5%), 14 (8.8%) cultures were contaminated and 22
      (13.8%) cultures were found to be negative. Using the immunochromatographic
      assay, Mycobacterium tuberculosis complex was detected in 118 (74.2%) liquid
      cultures, and 41 (25.8%) tests were negative. Sensitivity, specificity, positive
      and negative predictive values of the test were 98.3%; 97.5%; 99.15% i 95.12%,
      respectively. The value of kappa test was 0.950, and McNemar test was 1.00. The
      immunochromatographic assay is a simple and rapid test which represents a
      suitable alternative to the conventional subculture method for the primary
      identification of Mycobacterium tuberculosis complex in liquid cultures of
      BacT/Alert automated system.

PMID- 22364302
TI  - Intrauterine blood transfusion in immune hydrops fetalis, corrects middle
      cerebral artery Doppler velocimetry very quickly.
AB  - The aim of our study was to evaluate the middle cerebral artery velocimetry
      before and after intrauterine blood transfusion in immune hydrops fetalis. The
      current study was conducted in a tertiary research hospital, from February 2009
      to January 2011. Nineteen intrauterine blood transfusions performed during the
      study period. The factors recorded were age of the mothers, gestational weeks,
      pre-transfusion fetal hematocrit and post-transfusion fetal hematocrit, and also
      middle cerebral artery peak systolic velocimetry (MCA-PSV) was detected and
      recorded before and after intrauterine transfusion. A control group of twenty two
      cases for normal MCA doppler velocimetry was also included to the study. During
      the study, a total of eleven rhesus isoimmunized pregnancies underwent
      intrauterine blood transfusions at our perinatal diagnose unit. Before
      transfusion seventeen severe and two moderate anemias were detected and mean MoM
      of MCA-PSV was 1.76+/-0.38 MoM. Post transfusion mean MoM of MCA-PSV in the
      patient group and control group were 1.08+/-0.22 MoM and 0.96+/-0.21 MoM,
      respectively. The mean MCA-PSV values were higher in RI fetuses than post
      transfusion and control group. In current study, we found that MCA-PSV is a
      valuable parameter in detecting fetal anemia requiring intrauterine transfusion
      and mean MCA-PSV values is higher than 1.5 MoM in fetuses with anemia. And also
      decrease in MCA-PSV just after transfusion in anemic fetuses showed the quick
      response of the fetus to correction of anemia.

PMID- 22364303
TI  - C-Erb-b2 oncogene expression in intraductal proliferative lesions of the breast.
AB  - The ductal intraepithelial neoplasia (DIN) classification which proposes new
      approaches to the diagnosis, terminology and differential diagnosis of
      intraductal proliferative lesions of the breast was applied to a series of female
      patients comprising C-erbB2 oncogene expression which may serve as an adjunct to
      the morphology by immunohistochemistry. The study was performed using the data of
      94 patients. There was no difficulty encountered in the diagnosis of intraductal
      hyperplasia (IDH). In patients with Atypical Ductal Hyperplasia (AIDH), the
      diagnosis could be made by using the 2-mm rule of the DIN classification in
      patients who exhibited cytologic and structural characteristics of Ductal
      Carcinoma in Situ (DCIS) alone or in conjunction with classical IDH patterns.
      However, in lesions that mimicked classical IDH patterns despite displaying
      cytological features of in situ carcinomas, the experience and view point of the
      pathologist played a more prominent role. When the DIN classification criteria
      were applied to grade DCIS lesions, although the system was found to be
      practical, it did not provide adequate differentiation in intermediate grade
      (grade II-DIN 2) patients and further improvement was considered desirable.
      Fourty-five cases (47.8%) IDH, 19 (20.2%) AIDH, and 30 (31.9%) were DCIS. There
      were statistically significant differences in the levels of c-erbB2 oncogene
      expression between IDH, AIDH and DCIS lesions (p<0.001). In DCISs, grade, cell
      size, pleomorphic nuclear atypia showed statistically significant associations
      with c-erbB2 oncogene expression. These results suggest that c-erbB2 oncogene
      expression is a valuable marker in the differential diagnosis and prognostic
      evaluation of patients with intraductal proliferative lesions.

PMID- 22364304
TI  - Morphological characteristics of pubic symphysis for age estimation of exhumed
      persons.
AB  - Suchey-Brooks method based on morphological features of pubic symphysis is a
      common method of age evaluation of human skeletal remains. The aim of the study
      was the classification of the examined samples into a particular phase according
      to Suchey-Brooks method, comparing the estimated age according to Suchey-Brooks
      with living age of the identified persons. The study was conducted on 120 pairs
      of pubic bones symphysis of male who disappeared from the area of north-west
      Bosnia during previous war, who were exhumed and the process of their
      identification was previously finished. The youngest person was 19 years old and
      the oldest 86. The study was retrospective, made by comparing the morphological
      characteristics of pubic symphysis pairs of the examined sample with Suchey
      Brooks standards. The statistical analysis of data obtained by the survey showed
      that the smallest deviations from the average were in phase II by Suchey-Brooks,
      while the maximum deviation was in phase IV. The standard deviation generally
      increases from phase to phase, which is to be expected. The span of age obtained
      for Bosnian population is smaller at all stages in relation to Suchey Brooks
      standards, as well as standard deviation, except in phases IV and VI. There was a
      significant difference noticed in phase V in the estimation of age between the
      original method and Bosnian population. In general, Suchey-Brooks method leads to
      underestimation of age, but the underestimation or overestimation in relation to
      the actual age is possible at each stage, which indicates the individual
      biological variation.

PMID- 22364305
TI  - Microscopic polyangiitis presented with polyneuropathy of lower extremities and
      ANCA-associated glomerulonephritis: case report.
AB  - We present the case of a 67-year-old female patient with microscopic polyangiitis
      presented with polyneuropathy of lower extremities and rapidly progressive
      glomerulonephritis. Disease had started as a pain and weakening of muscular
      strength first in the left and than in the right leg. Electromiography has shown
      that a mainly dominant neurological affection was paresis of peroneal nerve in
      both lower extremities. In laboratory examination the titer of anti
      myeloperoxidase anti-neutrophilic cytoplasmic antibodies (p-ANCA) was elevated.
      Due to renal involvement presented as a microscopic haematuria and decreasing of
      renal function, patient undergone kidney biopsy. It confirmed the immune
      vasculitis microscopic polyangiitis type with ANCA-associated glomerulonephritis.
      This is one of rare case of microscopic polyangiitis without lung simptomatology,
      first presented with asymmetrical polineuropathy of lower extremities. The
      patient was treated with methylprednisolone and cyclophosphamide in dosis
      adjusted to the level of disease severity and the renal function
      (methylprednisolone 1 mg/kg of body weight for two months with gradually tapering
      to the minimum effective dose and cyclophosphamide 1 mg/kg of body weight). This
      treatment lead to the partial remission of disease. In maintenance therapy
      azathioprin was introduced instead of cyclophosphamide.

PMID- 22364306
TI  - Is there an improvement on the Web sites of the national and international
      pharmaceutical companies in Turkey? A follow-up study.
AB  - OBJECTIVE: In this follow-up study, we aimed to assess national and international
      pharmaceutical companies' Web sites using guidelines of The Association of
      Research-Based Pharmaceutical Companies (AIFD) and Pharmaceutical Manufacturers
      Association of Turkey (IEIS) to define whether there has been progress since
      2004. MATERIALS AND METHODS: We used two national guidelines in order to evaluate
      the Web sites of pharmaceutical companies in our study. The first guideline was
      from IEIS, and the second was from AIFD, which was issued recently. We collected
      our data between February 1 and April 30, 2011. Data analyses were performed
      using SPSS version 15.0. Chi squared test was done for comparing the two
      assessments in different years (2004 and 2011). RESULTS: In general, the progress
      that we were expecting was not satisfactory for both the international and
      national companies. The percentage of unmet criteria increased for "links" (from
      48.0% to 52.0%) and for "mentioning the responsible person/firm for the Web site
      design" (from 40.6% to 59.4%) among national companies. We observed statistically
      significant progress only for the "information for the public" criterion (from
      52.9% to 100%) among international companies. On the other hand, there was
      progress and a statistically significant difference in terms of not displaying
      any "drug ads" on the Web sites of national firms (from 55.9% to 87.5%),
      availability of "mail address" (from 88.2% to 100%), "telephone number" (from
      88.2% to 100%), "indication of the target group" (from 23.5% to 52.1%), and
      "disclaimer stating the given information cannot replace a physician or
      pharmacist" (from 29.4% to 53.1%). CONCLUSIONS: Our major recommendation to
      pharmaceutical companies is to update their Web sites with evidence-based
      scientific information about themselves and their products using international
      and national standards. From the companies' perspective, this should be a
      priority responsibility based on the ethical aspect of individual and community
      health.

PMID- 22364307
TI  - Should you search the Internet for information about your acute symptom?
AB  - OBJECTIVE: To determine if symptom-related Web sites give sufficient information
      for users to seek urgent care when warranted. MATERIALS AND METHODS: We reviewed
      120 Web sites (15 sites for each of eight acute symptoms). Symptom-related sites
      were identified with Google, Yahoo!(r), and BingTM searches and focused on
      potentially hazardous symptoms such as chest pain, shortness of breath, abdominal
      pain, and syncope. We reviewed each symptom-related site for the presence of
      critical symptom indicators (key symptom characteristics and associated factors)
      that triage the user to urgent care. RESULTS: Of the 120 sites reviewed, 41 (33%)
      contained no critical symptom indicators. No site contained a complete set of
      critical symptom indicators. Overall, out of the 1,020 total critical symptoms
      searched for in the sites, we only found 329 (32%). When present, critical
      symptom indicators were found on the top half of the first page of the site in
      only 34%. Specific recommendations for further care were absent in 42% of the
      cases where critical symptom indicators were identified. CONCLUSIONS: Symptom
      related sites ranked highly by major search engines lack much of the information
      needed to make a decision about whether a symptom needs urgent attention. When
      present, this information is usually not located where users can rapidly access
      it and often lacks prescriptive guidance for users to seek care. Until more sites
      contain at least minimal triage advice, relying on an Internet search to help
      determine the urgency of a symptom could be risky.

PMID- 22364308
TI  - Self-reported "communication technology" usage in patients attending a cardiology
      outpatient clinic in a remote regional hospital.
AB  - PURPOSE: This study assessed the perceived usage of, and attitudes toward,
      communication technologies (mobile phone and texting, e-mail, and the World Wide
      Web) in patients attending a cardiology clinic with a view to guiding future
      health service redesign. METHODS: This was performed in a remote regional
      hospital serving both urban and rural populations. A self-completion
      questionnaire was completed by a convenience sample of 221 patients attending a
      general cardiology clinic. The questions asked about patients' access to and use
      of technology at home. Data collected also included age, gender, travel time to
      the clinic, mode of travel, and whether the respondent was accompanied to the
      clinic. Appropriate statistical tests were used with significance taken at the
      0.05 level. FINDINGS: Age was the strongest predictor of use of communication
      technologies, with younger patients more likely to use e-mail, Web, mobile phone,
      and texting. However, frequency of use of e-mail was not related to age. It is
      encouraging that over 99% of patients used at least one communication technology.
      CONCLUSIONS: This study has highlighted that there may be several potential
      barriers to the widespread implementation of communication technologies in
      general cardiology patients. Cognizance should be taken of these findings when
      attempting service redesign.

PMID- 22364309
TI  - Effect of spinal cord stimulation in patients with refractory angina: evidence
      from observational studies.
AB  - OBJECTIVES:   To review the evidence in observational studies of the effect of
      spinal cord stimulation (SCS) in patients with refractory angina pectoris (RAP)
      due to obstructive coronary artery disease. The effect of SCS in patients with
      refractory microvascular angina (MVA) also was assessed. MATERIALS AND METHODS:  
      We reviewed the observational studies, published from 1987 to 2010, which
      investigated the effects of SCS on RAP. The number of angina attacks and that of
      taken nitrate tablets, as well as the class of angina, were considered as main
      outcome variables. The occurrence of adverse events related to the treatment also
      was assessed. RESULTS:   The results showed a consistent reduction of the number
      of angina attacks (by 45-84%) and of consumption of short-acting nitrate tablets
      (by -75% to -94%), whereas the New York Heart Association and Canadian
      Cardiovascular Society class of angina were significantly improved in some
      studies. No case fatalities related to the therapy were reported. Significant
      clinical benefits were observed in some studies in patients with refractory MVA.
      Device-related infections and catheter dislodgment were the most significant and
      frequent side-effects, respectively. CONCLUSIONS:   In observational studies, SCS
      showed to be an effective form of treatment for RAP, including refractory MVA.
      The treatment appears to be safe both at short- and long-term follow-up.

PMID- 22364310
TI  - Influence of wet distillers grains diets on beef cattle fecal bacterial community
      structure.
AB  - BACKGROUND: The high demand for ethanol in the U.S. has generated large stocks of
      wet distillers grains (DG), a byproduct from the manufacture of ethanol from corn
      and sorghum grains. Little is known, however, about the potential influence of
      dietary DG on fecal microbial community structure. A better understanding of the
      microbial population in beef cattle feces could be an important monitoring tool
      to facilitate goals of improving nutrient management, increasing animal growth
      performance and decreasing odors and/or shedding of pathogens. Five diets
      consisting of a traditional diet fed to finishing beef cattle in the Southern
      High Plains of Texas-CON (steam-flaked corn control with 0% DG), and four
      concentrations of DG in the dietary dry matter; 10 C (10% corn-based DG), 5S (5%
      sorghum-based DG), 10S (10% sorghum DG), and 15S (15% sorghum DG) were fed to
      steers at the Texas Tech University Burnett Animal Center. Diets were essentially
      isonitrogenous with a formulated crude protein value of 13.5%. RESULTS: Fecal
      grab samples were obtained from 20 steers (n = 4 per diet) and the barcoded DNA
      pyrosequencing method was used to generate 127,530 16S operational taxonomic
      units (OTUs). A total of 24 phyla were observed, distributed amongst all beef
      cattle on all diets, revealing considerable animal to animal variation, however
      only six phyla (core set) were observed in all animals regardless of dietary
      treatment. The average abundance and range of abundance, respectively of the core
      phyla were as follows: Firmicutes (61%, 19 to 83%), Bacteroidetes (28%, 11 to
      63%), Proteobacteria (3%, 0.34 to 17.5%), Tenericutes (0.15%, 0.0 to 0.35%),
      Nitrospirae (0.11%, 0.03 to 0.22%), and Fusobacteria (0.086%, 0.017 to 0.38%).
      Feeding DG-based diets resulted in significant shifts in the fecal microbial
      community structure compared with the traditional CON. Four low abundance phyla
      significantly responded to dietary treatments: Synergistetes (p = 0.01), WS3 (p =
      0.054), Actinobacteria (p = 0.06), and Spirochaetes (p = 0.06). CONCLUSIONS: This
      is, to our knowledge, the first study using this method to survey the fecal
      microbiome of beef cattle fed various concentrations of wet DG. Comparison of our
      results with other cattle DNA sequencing studies of beef and dairy cattle feces
      from a variety of geographical locations and different management practices
      identifies a core set of three phyla shared across all cattle. These three phyla,
      in order of relative abundance are; Firmicutes, Bacteroidetes, and
      Proteobacteria. The presence of large animal-to-animal variation in cattle
      microbiome was noted in our study as well as by others.

PMID- 22364311
TI  - How do the different components of episodic memory develop? Role of executive
      functions and short-term feature-binding abilities.
AB  - This study investigated the development of all 3 components of episodic memory
      (EM), as defined by Tulving, namely, core factual content, spatial context, and
      temporal context. To this end, a novel, ecologically valid test was administered
      to 109 participants aged 4-16 years. Results showed that each EM component
      develops at a different rate. Ability to memorize factual content emerges early,
      whereas context retrieval abilities continue to improve until adolescence, due to
      persistent encoding difficulties (isolated by comparing results on free recall
      and recognition tasks). Exploration of links with other cognitive functions
      revealed that short-term feature-binding abilities contribute to all EM
      components, and executive functions to temporal and spatial context, although
      ability to memorize temporal context is predicted mainly by age.

PMID- 22364312
TI  - Renal resistive index as a new independent risk factor for new-onset diabetes
      mellitus after kidney transplantation.
AB  - Pulse pressure and urinary albumin excretion were recently identified as risk
      factors of new-onset diabetes after renal transplantation (NODAT), suggesting
      that microvascular injury may be implicated in NODAT. However, the relationship
      between of microvascular injury and NODAT is unknown. In the present long-term
      (median follow-up: 5.7years; observation period: 4908 patient-years)
      retrospective study in 656 renal transplant recipients, the association between
      baseline renal resistance index (RI, used as a marker of widespread microvascular
      damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2%
      and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months
      was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09),
      P<0.0001]. RI >0.75 (vs. 0<=0.75) was a potent a predictor of NODAT [HR: 3.29
      (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030]
      on age, weight, glucose, nephropathy, and arterial pressure. Similar results were
      observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001]
      and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High
      RI early after renal transplantation is a long-term risk factor for NODAT, and
      could be used to refine the individual risk of NODAT.

PMID- 22364313
TI  - Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates
      the killing activity against Candida albicans.
AB  - Bovine lactoferrin harbors 2 antimicrobial sequences (LFcin and LFampin),
      situated in close proximity in the N1-domain. To mimic their semi parallel
      configuration we have synthesized a chimeric peptide (LFchimera) in which these
      sequences are linked in a head-to-head fashion to the alpha- and epsilon-amino
      group, respectively, of a single lysine. In line with previously described
      bactericidal effects, this peptide was also a stronger candidacidal agent than
      the antimicrobial peptides LFcin17-30 and LFampin265-284, or a combination of
      these 2. Conditions that strongly reduced the candidacidal activities of LFcin17
      30 and LFampin265-284, such as high ionic strength and energy depletion, had
      little influence on the activity of LFchimera. Freeze-fracture electron
      microscopy showed that LFchimera severely affected the membrane morphology,
      resulting in disintegration of the membrane bilayer and in an efflux of small and
      high molecular weight molecules such as ATP and proteins. The differential
      effects displayed by the chimeric peptide and a mixture of its constituent
      peptides clearly demonstrate the synergistic effect of linking these peptides in
      a fashion that allows a similar spatial arrangement as in the parent protein,
      suggesting that in bovine lactoferrrin the corresponding fragments act in concert
      in its candidacidal activity.

PMID- 22364314
TI  - Co-evolution and symbiont replacement shaped the symbiosis between adelgids
      (Hemiptera: Adelgidae) and their bacterial symbionts.
AB  - The Adelgidae (Insecta: Hemiptera), a small group of insects, are known as severe
      pests on various conifers of the northern hemisphere. Despite of this, little is
      known about their bacteriocyte-associated endosymbionts, which are generally
      important for the biology and ecology of plant sap-sucking insects. Here, we
      investigated the adelgid species complexes Adelges laricis/tardus, Adelges
      abietis/viridis and Adelges cooleyi/coweni, identified based on their coI and
      ef1alpha genes. Each of these insect groups harboured two phylogenetically
      different bacteriocyte-associated symbionts belonging to the Betaproteobacteria
      and the Gammaproteobacteria, respectively, as inferred from phylogenetic analyses
      of 16S rRNA gene sequences and demonstrated by fluorescence in situ
      hybridization. The betaproteobacterial symbionts of all three adelgid complexes
      ('Candidatus Vallotia tarda', 'Candidatus Vallotia virida' and 'Candidatus
      Vallotia cooleyia') share a common ancestor and show a phylogeny congruent with
      that of their respective hosts. Similarly, there is evidence for co-evolution
      between the gammaproteobacterial symbionts ('Candidatus Profftia tarda',
      'Candidatus Profftia virida') and A. laricis/tardus and A. abietis/viridis. In
      contrast, the gammaproteobacterial symbiont of A. cooleyi/coweni ('Candidatus
      Gillettellia cooleyia') is different from that of the other two adelgids but
      shows a moderate relationship to the symbiont 'Candidatus Ecksteinia
      adelgidicola' of A. nordmannianae/piceae. All symbionts were present in all
      adelgid populations and life stages analysed, suggesting vertical transmission
      from mother to offspring. In sharp contrast to their sister group, the aphids,
      adelgids do not consistently contain a single obligate (primary) symbiont but
      have acquired phylogenetically different bacterial symbionts during their
      evolution, which included multiple infections and symbiont replacement.

PMID- 22364315
TI  - Tumor accumulation, penetration, and antitumor response of cisplatin-loaded
      gelatin/poly(acrylic acid) nanoparticles.
AB  - In this report, the cisplatin (CDDP)-loaded gelatin/poly(acrylic acid) (GEL-PAA)
      nanoparticles with a spherical shape and drug loading content of 24.6% were
      prepared. In vivo near-infrared fluorescence (NIRF) imaging and ex vivo gamma
      scintillation counting analyses reveal that CDDP-loaded GEL-PAA nanoparticles
      have prominent passive tumor-targeting ability and the nontarget nanoparticles
      can be readily excreted from the body. Further, it is demonstrated that the CDDP
      loaded nanoparticles have the ability to penetrate the tumor after their
      extravasation through the leaky vessels and distribute in a distance of about 20
      MUm from the vessels at 24 h postinjection. The in vivo antitumor responses
      reveal that the nanoparticle formulation exhibits significantly superior in vivo
      antitumor effect than free CDDP by the comparison of tumor volume and the
      examinations of cell apoptosis and proliferation in tumor tissues through
      proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl
      transferase-mediated nick end labeling (TUNEL) methods.

PMID- 22364316
TI  - Sustained efficacy of ustekinumab in refractory erythrodermic psoriasis after
      failure of antitumor necrosis factor therapies.

PMID- 22364317
TI  - Optimizing the reinforcement of polymer-based nanocomposites by graphene.
AB  - The stress transfer between the internal layers of multilayer graphene within
      polymer-based nanocomposites has been investigated from the stress-induced shifts
      of the 2D Raman band. This has been undertaken through the study of the
      deformation of an ideal composite system where the graphene flakes were placed
      upon the surface of a polymer beam and then coated with an epoxy polymer. It is
      found that the rate of band shift per unit strain for a monolayer graphene flake
      is virtually independent of whether it has one or two polymer interfaces (i.e.,
      with or without an epoxy top coating). In contrast, the rate of band shift is
      lower for an uncoated bilayer specimen than a coated one, indicating relatively
      poor stress transfer between the graphene layers. Mapping of the strain in the
      coated bilayer regions has shown that there is strain continuity between adjacent
      monolayer and bilayer regions, indicating that they give rise to similar levels
      of reinforcement. Strain-induced Raman band shifts have also been evaluated for
      separate flakes of graphene with different numbers of layers, and it is found
      that the band shift rate tends to decrease with an increase in the number of
      layers, indicating poor stress transfer between the inner graphene layers. This
      behavior has been modeled in terms of the efficiency of stress transfer between
      the inner graphene layers. Taking into account the packing geometry of polymer
      based graphene nanocomposites and the need to accommodate the polymer coils,
      these findings enable the optimum number of graphene layers for the best
      reinforcement to be determined. It is demonstrated that, in general, multilayer
      graphene will give rise to higher levels of reinforcement than monolayer
      material, with the optimum number of layers depending upon the separation of the
      graphene flakes in the nanocomposite.

PMID- 22364318
TI  - Effect of organic matter on the in vitro photoeradication of Pseudomonas
      aeruginosa by means of a cationic tetraaryl-porphyrin.
AB  - Photodynamic therapy is emerging as an antimicrobial alternative approach; the
      concomitant presence of a photosensitizer (PS), O(2)  and visible light induces
      lethal oxidative damages to bacterial cells. Among Gram-negative bacteria,
      Pseudomonas aeruginosa seems to be one of the least susceptible to photodynamic
      treatment. In this study, we evaluated the influence of several experimental
      conditions on photoeradication of a planktonic culture of P. aeruginosa PAO1 by
      means of a tetracationic meso-arylsubstituted porphyrin (RM24). Our findings
      suggest that the photo-oxidative stress induced by RM24 is strictly correlated to
      the amount of PS bound to the cells that in turn decreases with the increasing
      concentrations of organic compounds in the medium. The photoeradication is
      dependent on PS concentrations, cellular density and light dose. RM24 was able to
      induce oxidative stress by means of singlet oxygen formation, although ROS
      formation cannot be ruled out. The standardized experimental conditions of the
      photospot test allowed us to evidence intraspecific PDT sensitivity differences
      among three strains of P. aeruginosa.

PMID- 22364319
TI  - Principles of nuclear medicine imaging: planar, SPECT, PET, multi-modality, and
      autoradiography systems.
AB  - The underlying principles of nuclear medicine imaging involve the use of unsealed
      sources of radioactivity in the form of radiopharmaceuticals. The ionizing
      radiations that accompany the decay of the administered radioactivity can be
      quantitatively detected, measured, and imaged in vivo with instruments such as
      gamma cameras. This paper reviews the design and operating principles, as well as
      the capabilities and limitations, of instruments used clinically and
      preclinically for in vivo radionuclide imaging. These include gamma cameras,
      single-photon emission computed tomography (SPECT) scanners, and positron
      emission tomography (PET) scanners. The technical basis of autoradiography is
      reviewed as well.

PMID- 22364322
TI  - What is the best drug-delivery approach for the acute treatment of migraine?

PMID- 22364321
TI  - Metal organic chemical vapor deposition of phase change Ge1Sb2Te4 nanowires.
AB  - The self-assembly of Ge(1)Sb(2)Te(4) nanowires (NWs) for phase change memories
      application was achieved by metal organic chemical vapor deposition, catalyzed by
      Au nanoislands in a narrow range of temperatures and deposition pressures. In the
      optimized conditions of 400  degrees C, 50 mbar, the NWs are Ge(1)Sb(2)Te(4)
      single hexagonal crystals. Phase change memory switching was reversibly induced
      by nanosecond current pulses through metal-contacted NWs with threshold voltage
      of about 1.35 V.

PMID- 22364320
TI  - Rhodium-catalyzed intra- and intermolecular [5 + 2] cycloaddition of 3-acyloxy
      1,4-enyne and alkyne with concomitant 1,2-acyloxy migration.
AB  - A new type of rhodium-catalyzed [5 + 2] cycloaddition was developed for the
      synthesis of seven-membered rings with diverse functionalities. The ring
      formation was accompanied by a 1,2-acyloxy migration event. The five- and two
      carbon components of the cycloaddition are 3-acyloxy-1,4-enynes (ACEs) and
      alkynes, respectively. Cationic rhodium(I) catalysts worked most efficiently for
      the intramolecular cycloaddition, while only neutral rhodium(I) complexes could
      facilitate the intermolecular reaction. In both cases, electron-poor phosphite or
      phosphine ligands often improved the efficiency of the cycloadditions. The scope
      of ACEs and alkynes was investigated in both the intra- and intermolecular
      reactions. The resulting seven-membered-ring products have three double bonds
      that could be selectively functionalized.

PMID- 22364323
TI  - Testosterone and suicidal behavior.

PMID- 22364325
TI  - Lurasidone for schizophrenia: what's different?
AB  - Lurasidone is one of several antipsychotics approved in the recent past by the US
      FDA for the treatment of schizophrenia. Several Phase II and III studies have
      established that lurasidone is more efficacious than placebo. There are no
      available adequately powered head-to-head comparisons of efficacy of lurasidone
      with other antipsychotics. However, in contrast to some other antipsychotics,
      lurasidone is associated with minimal weight gain and no clinically meaningful
      alterations in glucose, lipids, or the ECG QT interval. As per the product label,
      the recommended starting dose is 40 mg/day and the maximum recommended dose is 80
      mg/day. Higher doses do not appear to be more efficacious, and may be associated
      with increases in adverse effects, such as somnolence and akathisia; however,
      this tolerability issue was not observed in one recently conducted 6-week study
      when lurasidone was administered at a dose of 160 mg/day. It is recommended that
      lurasidone be administered once daily with at least 350 calories of food.
      Additional studies are desirable to directly compare and contrast lurasidone with
      other antipsychotic agents.

PMID- 22364326
TI  - Vigabatrin monotherapy for infantile spasms.
AB  - Infantile spasms syndrome (IS) (also known as West syndrome) is an epileptic
      encephalopathy with a heterogeneous etiology. One of the most common specific
      causes is tuberous sclerosis, diagnosed in almost 10% of the affected infants.
      Adrenocorticotropic hormone or steroids have been the preferred treatments for IS
      for several decades. Clinical studies have shown that vigabatrin is superior to
      placebo in decreasing the frequency of infantile spasms. In tuberous sclerosis,
      vigabatrin may be considered the first-line treatment for IS. The mode of action
      is increasing concentrations of the inhibitory neurotransmitter GABA in the
      brain. The use of vigabatrin is limited by a serious adverse effect, permanent
      visual field constriction, which may affect 6-7% of exposed infants. Treatment
      choices are based on balancing the potential adverse effects against the risk of
      catastrophic cognitive and behavioral outcomes caused by uncontrolled spasms.

PMID- 22364327
TI  - Prevalence, clinical features and potential therapies for fibromyalgia in primary
      headaches.
AB  - Fibromyalgia (FM) syndrome is predominantly related to generation and persistence
      of central sensitization, which is an aggravating factor for chronic headaches.
      This review aims to examine the last 11 years of studies on FM and primary
      headache comorbidity, focusing on prevalence, clinical features and treatments.
      Chronic forms of migraine and tension-type headache show a high frequency of FM
      comorbidity. The symptoms characterizing headache patients presenting with FM
      comorbidity are high headache frequency, poor sleep quality, pericranial
      tenderness, anxiety and reduction of physical performances. The effects of
      headache-preventive drugs on factors favoring FM comorbidity were poorly
      evaluated. Nonpharmacological approaches such as transcranial magnetic
      stimulation may be an option for treatment of chronic migraine associated with
      FM.

PMID- 22364329
TI  - Acute confusional migraine: our knowledge to date.
AB  - Acute confusional migraine (ACM) is a rare migraine variant, affecting children
      and adolescents, as well as adults. Between 0.45 and 7.8% of children with
      migraine present with ACM, but the disorder may well be underdiagnosed. ACM is an
      exclusion diagnosis and some dangerous causes of confusion (e.g., epilepsy,
      ischemia, hemorrhagia, neoplasm, intoxication and encephalitis) should be ruled
      out. The confusional state often manifests with a wide diversity of cortical
      dysfunctions, such as speech difficulties, increased alertness, agitation and
      amnesia. Exact history taking, clinical examination, and laboratory, radiological
      and electroencephalographical findings lead the practitioner towards the
      diagnosis. Approximately half of the cases may be triggered by mild head trauma.
      Transient global amnesia is an important differential diagnosis, possibly caused
      by similar pathophysiological mechanisms. The exact pathomechanism remains
      unclear, with the common hypothesis comprising of the confusional state as a
      complex aura phenomenon, in which the cortical spreading depression wave reaches
      not only the occipital, but also the temporal, parietal and frontal cortex, as
      well as the brainstem and the hippocampi, leading to transient hypoperfusion and
      dysfunction of these brain areas.

PMID- 22364330
TI  - Muscle trigger point therapy in tension-type headache.
AB  - Recent evidence suggests that active trigger points (TrPs) in neck and shoulder
      muscles contribute to tension-type headache. Active TrPs within the suboccipital,
      upper trapezius, sternocleidomastoid, temporalis, superior oblique and lateral
      rectus muscles have been associated with chronic and episodic tension-type
      headache forms. It seems that the pain profile of this headache may be provoked
      by referred pain from active TrPs in the posterior cervical, head and shoulder
      muscles. In fact, the presence of active TrPs has been related to a higher degree
      of sensitization in tension-type headache. Different therapeutic approaches are
      proposed for proper TrP management. Preliminary evidence indicates that
      inactivation of TrPs may be effective for the management of tension-type
      headache, particularly in a subgroup of patients who may respond positively to
      this approach. Different treatment approaches targeted to TrP inactivation are
      discussed in the current paper, focusing on tension-type headache. New studies
      are needed to further delineate the relationship between muscle TrP inactivation
      and tension-type headache.

PMID- 22364328
TI  - Pharmacological targeting of spreading depression in migraine.
AB  - Migraine, particularly with aura, is a genetically heterogeneous disorder of ion
      channels, pumps or transporters associated with increased cortical excitability.
      Spreading depression, as one reflection of hyperexcitability, is the
      electrophysiological event underlying aura symptoms and a trigger for headache.
      Endogenous (e.g., genes and hormones) and exogenous factors (e.g., drugs)
      modulating migraine susceptibility have also been shown to modulate spreading
      depression susceptibility concordantly, suggesting that spreading depression can
      be a relevant therapeutic target in migraine. In support of this, several
      migraine prophylactic drugs used in clinical practice have been shown to suppress
      spreading depression susceptibility as a probable mechanism of action, despite
      belonging to widely different pharmacological classes. Hence, susceptibility to
      spreading depression can be a useful preclinical model with good positive and
      negative predictive value for drug screening.

PMID- 22364331
TI  - Clinical applications of imaging disease burden in multiple sclerosis: MRI and
      advanced imaging techniques.
AB  - This review will address the critical role of radiographic techniques in
      monitoring multiple sclerosis disease course and response to therapeutic
      interventions using conventional imaging. We propose an algorithm of obtaining a
      contrast-enhanced brain MRI 6 months after starting a disease-modifying therapy,
      and considering a gadolinium-enhancing lesion on that scan to indicate suboptimal
      response to therapy. New or enlarging T2 lesions should be followed on scans at 6
      month intervals to assess for change, and the presence of one or more enhancing
      lesions on a 6- or 12-month scan, or two or more new or enlarging T2 lesions on a
      12-month scan should prompt consideration of therapy change. New techniques such
      as PET imaging, magnetic resonance spectroscopy, magnetic resonance relaxometry,
      iron-sensitive imaging and perfusion MRI will also be overviewed, with their
      potential roles in monitoring disease course and activity.

PMID- 22364332
TI  - Secondary autoimmune diseases following alemtuzumab therapy for multiple
      sclerosis.
AB  - Alemtuzumab is a humanized monoclonal antibody that causes prolonged lymphopenia.
      In a recent Phase III trial, alemtuzumab was shown to reduce both the annualized
      relapse rate and the rate of sustained accumulation of disability by over 70%
      when compared with IFN-beta1a. However, the drug is associated with thyroid
      autoimmunity in approximately a third of treated patients, as well as other
      secondary autoimmune conditions in smaller numbers. Secondary autoimmunity
      typically arises during reconstitution of the lymphocyte repertoire. Individuals
      with high baseline circulating levels of IL-21 are at highest risk of developing
      autoimmunity following treatment with alemtuzumab.

PMID- 22364333
TI  - Participatory medicine and patient empowerment towards personalized healthcare in
      multiple sclerosis.
AB  - The current understanding that the key for successful healthcare is an integrated
      approach, involving predictive, preventive, personalized and participatory
      medicine, is leading major changes. These are: a shift from medical decisions
      based on 'trial and error' to informed therapeutics based on diagnostics
      (theranostics); a shift from a 'disease-centered' to a 'patient-centered'
      approach; and a shift from a 'reactive' to 'proactive' medical approach. It is
      essential that not only the physician, but also the patient, becomes proactive.
      Therefore, beyond the integration of genomic medicine and predictive biomarkers
      into practice, patient empowerment and participatory medicine are gaining
      increasing attention. This requires, besides appropriate sharing of information
      between patients and healthcare providers, new insights in patient involvement,
      such as patient-reported outcomes, both at the clinical trial stage of drug
      development and during post-marketing follow-up assessments. Patient empowerment
      and participatory medicine, as part of predictive, preventive, personalized and
      participatory medicine, are especially crucial in paving the way towards
      optimized healthcare in complex and chronic neurological diseases, such as
      multiple sclerosis.

PMID- 22364334
TI  - Insight and suicidal behavior in first-episode schizophrenia.
AB  - Suicidal behavior and suicide is prevalent in schizophrenia, with an estimated
      lifetime risk of approximately 5%. The risk is particularly high in the early
      phases of the disorder, and especially during the years around treatment
      initiation. Suicide attempts before first treatment contact are also prevalent,
      with the risk of suicide attempt associated with the length of untreated illness.
      Several risk factors are in common with the general population, and include
      previous suicide attempts, impulsive personality traits, substance abuse,
      depression and feelings of hopelessness. Recent research examines how patients'
      subjective experiences, including their insight into having a severe mental
      illness and their beliefs about mental illnesses, may influence suicidal
      behavior. In this article, we will present a review of studies illustrating the
      complex background of suicide risk in schizophrenia, with a particular emphasis
      on the role of insight in the early phases of schizophrenia.

PMID- 22364336
TI  - Is constant current or constant voltage spinal cord stimulation superior for the
      suppression of nociceptive visceral and somatic stimuli? A rat model.
AB  - OBJECTIVES: This study compares the effects of constant current (CC) and constant
      voltage (CV) spinal cord stimulation (SCS) at various frequencies and intensities
      on standard nociceptive measurements in rats, the visceromotor reflex (VMR) and
      neuronal activity, during noxious visceral and somatic stimuli. MATERIALS AND
      METHODS: Abdominal muscle electromyographic activity changes were measured to
      indicate VMR, and extracellular activity of L6-S2 spinal neurons was recorded
      during somatic (pinching) and noxious visceral stimulation (colorectal distension
      [CRD], 60 mmHg) in anesthetized rats. A stimulating (unipolar ball) electrode at
      L2-L3 delivered CC- or CV-SCS at varied frequencies and intensities. RESULTS: CC
      SCS reduced VMR evoked by CRD significantly more than CV-SCS (p < 0.05). For
      neuronal activity, high-frequency CC-SCS (40 and 100 Hz) and CV-SCS (100 Hz)
      effectively reduced intraspinal somatic nociceptive transmission more than low
      frequency SCS (2 Hz). No significant differences were observed between the
      effects of CC- and CV-SCS on spontaneous activity and nociceptive responses of
      spinal neurons to noxious CRD following short- (five to ten minutes) or long-term
      (20-30 min) SCS. CONCLUSIONS: Although high-frequency CC- and CV-SCS may be more
      useful for the management of somatic pain, CC-SCS may be more effective for
      treating complex pain systems like visceral hypersensitivity.

PMID- 22364337
TI  - Discovery of 1,4-disubstituted 3-cyano-2-pyridones: a new class of positive
      allosteric modulators of the metabotropic glutamate 2 receptor.
AB  - The discovery and characterization of compound 48, a selective and in vivo active
      mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the
      discovery was the rational exploration of the initial HTS hit 13 guided by an
      overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak
      in vitro activity of the hit 13 was quickly improved, although compounds still
      had suboptimal druglike properties. Subsequent modulation of the physicochemical
      properties resulted in compounds having a more balanced profile, combining good
      potency and in vivo pharmacokinetic properties. Final refinement by addressing
      cardiovascular safety liabilities led to the discovery of compound 48. Besides
      good potency, selectivity, and ADME properties, compound 48 displayed robust in
      vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with
      mGlu2 receptor activation, in accordance with previous work from our
      laboratories.

PMID- 22364338
TI  - Toward a possibility to exchange CO2 and CH4 in sI clathrate hydrates.
AB  - We study the thermodynamic conditions for exchange of CH(4) with CO(2) in sI
      clathrate hydrates using Grand Canonical Monte Carlo simulations. From the
      variations in the Helmholtz energy, we suggest a thermodynamic path for exchange
      of CH(4) by CO(2). The results can be understood from single-component occupancy
      isotherms. Simulations of pure component systems show that all methane sites are
      essentially equivalent, whereas carbon dioxide distinguishes between two types of
      sites, large or small. Mixture of CO(2) and CH(4) in the clathrate can be
      regarded as ideal, as long as only the large sites are occupied. A strong
      preference in selectivity is demonstrated for methane when the smaller sites
      become filled. The Helmholtz energies of the hydrate with a CO(2)-CH(4) gas
      mixture for temperatures between 278 and 328 K and pressures between 10(4) and
      10(9) Pa indicate that there exists a region of stability of a mixed hydrate
      referred to single-component hydrates.

PMID- 22364339
TI  - Effects of micromovement on the changes in stress distribution of partially
      stabilized zirconia (PS-ZrO2) dental implants and bridge during clenching: a
      three-dimensional finite element analysis.
AB  - OBJECTIVE: This investigation aims to evaluate the changes in stress magnitudes
      and distributions on Partially Stabilized Zirconia (PS-ZrO(2)) dental implants
      and bridges and on the mandible caused by fibrous encapsulations during
      clenching. MATERIALS AND METHODS: Four 3.26 mm diameter PS-ZrO(2) dental implants
      with lengths of 12 mm were modelled and placed in the second premolar and first
      molar region on both sides of the mandible model. A rigid zirconia bridge with a
      thickness of 0.5 mm connects the PS-ZrO(2) dental implants placed in the second
      premolar and first molar. Four periodontal ligament (PDL) case studies were
      examined: PDL in the second premolars; PDL in the first molars; PDL in both the
      second premolars and first molars; and no PDL present. RESULTS: The results
      reveal the magnitudes and distributions of stresses on the dental implants and
      connecting bridges were governed by the PDLs. A significant drop in stress levels
      were recorded when the PDL encapsulates the roots of the dental implants. Of the
      four PDL case studies, it was found that when the PDLs are present in both the
      second premolars and first molars the lowest stress magnitudes are generated. The
      analysis also revealed that, during the healing process after implant insertion
      and the result of fibrous encapsulation, the dental implant system will
      experience a varying amount of stress levels. CONCLUSION: This study was intended
      to produce more insight into the influence of the PDL on the changes in stress
      distribution on the dental implant system during clenching.

PMID- 22364341
TI  - Self-change in eating disorders: is "spontaneous recovery" possible?
AB  - A limited series of community studies including non-treatment-seekers has shown
      that a considerable number of eating disorder patients do not enter the health
      care system but can be considered "clinically recovered" (remission of major
      symptoms) if followed up long enough. The possibility of "spontaneous recovery"
      (overcoming an eating disorder without professional treatment or formal help)
      often faces scepticism on the part of professionals. Clearly, self-change is an
      underestimated pathway to recovery from an eating disorder, but open-minded
      clinicians can learn a lot from it. Active coping and making use of one's
      "recovery capital" are key features of self-change even if maintenance of change
      is associated with social support and positive life changes.

PMID- 22364342
TI  - Drive for muscularity and drive for thinness: the impact of pro-anorexia
      websites.
AB  - In recent years, websites that stress the message of thinness as the ideal and
      only choice have surfaced on the internet. The possibility that pro-anorexia
      websites may reinforce restrictive eating and exercise behaviors is an area of
      concern. In addition, friends may be influencing one another to view these
      websites, further contributing to drive for thinness in women and drive for
      muscularity in men. Three hundred male and female undergraduate psychology
      students responded to questionnaires assessing: internalization of pro-anorexia
      website content, internalization of general media content, influence of friends
      to view pro-anorexia websites, peer influence, drive for muscularity, and drive
      for thinness. Results showed internalization of pro-anorexia website content was
      positively correlated with drive for thinness in women, and negatively correlated
      with drive for muscularity in men. Internalization of pro-anorexia website
      content was found to be related to both drive for thinness in women and drive for
      muscularity in men.

PMID- 22364340
TI  - Minocycline markedly reduces acute visceral nociception via inhibiting neuronal
      ERK phosphorylation.
AB  - BACKGROUND: Minocycline prevents the development of neuropathic and inflammatory
      pain by inhibiting microglial activation and postsynaptic currents. But, how
      minocycline obviates acute visceral pain is unclear. The present study
      investigated whether minocycline had an any antinociceptive effect on acetic acid
      induced acute abdominal pain after intraperitoneal (i.p.) administration of
      saline or minocycline 1 hour before acetic acid injection (1.0%, 250 MUl, i.p.).
      RESULTS: Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid
      induced nociception (0-60 minutes post-injection) and the enhancement in the
      number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid
      injection. Also, the expression of spinal phosphorylated extracellular signal
      regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre
      administration. Interestingly, intrathecal introduction of PD98059, an ERK
      upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain
      responses. CONCLUSIONS: These results demonstrate that minocycline effectively
      inhibits acetic acid-induced acute abdominal nociception via the inhibition of
      neuronal p-ERK expression in the spinal cord, and that minocycline may have
      therapeutic potential in suppressing acute abdominal pain.

PMID- 22364343
TI  - Evaluating the effects of a peer-support model: reducing negative body esteem and
      disordered eating attitudes and behaviours in grade eight girls.
AB  - During adolescence girls become increasingly preoccupied with unrealistic ideals
      about body weight, often leading to dieting and unhealthy compensatory
      behaviours. These practices have been linked to adverse psychological, social,
      and health consequences. Peer-support groups offer promise in addressing risk
      factors for disordered eating. This study explored the effects of peer-support on
      measures of body satisfaction, weight loss/weight gain behaviour, internalization
      of media ideals, weight based teasing, and communication, for a cohort of grade 8
      girls. High-risk participants demonstrated trends toward decreased
      internalization of media ideals and increased body satisfaction at post-test.
      Implications and future research direction are discussed.

PMID- 22364344
TI  - Using the implicit relational assessment procedure to compare implicit pro
      thin/anti-fat attitudes of patients with anorexia nervosa and non-clinical
      controls.
AB  - Implicit pro-thin/anti-fat attitudes were investigated among a mixed group of
      patients with full and sub-threshold Anorexia Nervosa (n = 17), and a matched-age
      control group (n = 17). The Implicit Relational Assessment Procedure (IRAP) was
      employed to measure implicit pro-thin and anti-fat attitudes towards Self and
      Others in addition to "striving for thinness" and "avoidance of fatness." The
      clinical group showed an implicit pro-fat attitude towards Others and stronger
      anti-fat attitudes towards Self and avoidance of fatness compared with controls.
      The findings are discussed in relation to the over-evaluation of weight and shape
      in the clinical group.

PMID- 22364345
TI  - Discerning thoughts from feelings: the cognitive-affective division in eating
      disorders.
AB  - This article delineates the phenomenon of "cognitive-affective division" in
      eating disorders, used to refer to the difficulty some patients face in
      translating what they "think" cognitively to what they "feel" emotionally. A
      clinical description of cognitive-affective division is first presented, drawing
      on existing research, before moving on to discuss psychological theories that
      might shed some light on this often-seen but seldom understood phenomenon. These
      include the role of emotion awareness and alexithymia, cognitive and emotional
      development, and neuropsychological theories. We discuss implications for
      treatment and further research of the cognitive-affective division in eating
      disorders.

PMID- 22364346
TI  - Effect of non-select menus on weight and eating concern in adolescents
      hospitalized with anorexia nervosa.
AB  - The objective of this study was to assess the impact of food service menu type
      (i.e., non-select versus select) on weight restoration and eating concern for
      adolescent patients hospitalized with Anorexia Nervosa. Charts of 40 adolescents
      (mean age 13.3 +/- 2.2 years) were reviewed. Rate of weight gain was
      significantly increased when non-select menus were used (0.95 kg/wk versus 0.72
      kg/wk [p < .03]). No significant differences in total weight gain, length of
      stay, or eating concern were observed. Non-select menus significantly increase
      rate of weight restoration in children and adolescents hospitalized with Anorexia
      Nervosa.

PMID- 22364351
TI  - Tuning the optical property and photocatalytic performance of titanate nanotube
      toward selective oxidation of alcohols under ambient conditions.
AB  - Titanate nanotube (TNT) represents one class of novel one-dimensional
      semiconducting nanomaterials that can be used as photocatalyst for given
      applications. However, TNT is only UV-light photoactive because of its intrinsic
      limitation of light absorption in the UV region. Here, we report a facile
      approach to tune the optical property and photocatalytic performance of TNT by
      doping various metal ions (Cu(2+), Co(2+), Ni(2+), Fe(2+), and Mn(2+)) via an ion
      exchange method in an aqueous phase. The optical properties of TNT can be finely
      tuned by incorporating different kinds of metal ions into its tubular framework.
      In particular, the incorporation of metal ions into the matrix of TNT is able to
      extend its light absorption to the visible-light region, thus making TNT have the
      visible-light photoactivity. Activity testing on photocatalytic selective
      oxidation of a variety of benzylic and allylic alcohols under mild conditions
      demonstrates that these metal-ion-doped TNTs exhibit markedly enhanced catalytic
      performance as compared to the undoped TNTs under both the irradiation of UV
      light and visible light. Such an enhancement of photocatalytic activity with
      regard to metal-ion-doped TNT is primarily attributed to the prolonged lifetime
      of photogenerated electron-hole pairs in comparison with that of undoped TNT. Our
      current research work demonstrates the tunable optical property of TNT by doping
      metal ions and, more significantly, opens promising prospects of one-dimensional
      nanotubular TNT or TNT-based materials as visible-light-driven photocatalyst in
      the area of selective transformation using molecular oxygen as benign oxidant
      under ambient conditions.

PMID- 22364350
TI  - Biomimetically mineralized salmon collagen scaffolds for application in bone
      tissue engineering.
AB  - Biomimetic mineralization of collagen is an advantageous method to obtain
      resorbable collagen/hydroxy-apatite composites for application in bone
      regeneration. In this report, established procedures for mineralization of bovine
      collagen were adapted to a new promising source of collagen from salmon skin
      challenged by the low denaturation temperature. Therefore, in the first instance,
      variation of temperature, collagen concentration, and ionic strength was
      performed to reveal optimized parameters for fibrillation and simultaneous
      mineralization of salmon collagen. Porous scaffolds from mineralized salmon
      collagen were prepared by controlled freeze-drying and chemical cross-linking. FT
      IR analysis demonstrated the mineral phase formed during the preparation process
      to be hydroxyapatite. The scaffolds exhibited interconnecting porosity, were
      sufficiently stable under cyclic compression, and showed elastic mechanical
      properties. Human mesenchymal stem cells were able to adhere to the scaffolds,
      cell number increased during cultivation, and osteogenic differentiation was
      demonstrated in terms of alkaline phosphatase activity.

PMID- 22364352
TI  - Find your manners: how do infants detect the invariant manner of motion in
      dynamic events?
AB  - To learn motion verbs, infants must be sensitive to the specific event features
      lexicalized in their language. One event feature important for the acquisition of
      English motion verbs is the manner of motion. This article examines when and how
      infants detect manners of motion across variations in the figure's path.
      Experiment 1 shows that 13- to 15-month-olds (N = 30) can detect an invariant
      manner of motion when the figure's path changes. Experiment 2 reveals that
      reducing the complexity of the events, by dampening the figure's path, helps 10-
      to 12-month-olds (N = 19) detect the invariant manner. These findings suggest
      that: (a) infants notice event features lexicalized in English motion verbs, and
      (b) attention to manner can be promoted by reducing event complexity.

PMID- 22364353
TI  - Metatranscriptomics of the marine sponge Geodia barretti: tackling phylogeny and
      function of its microbial community.
AB  - Geodia barretti is a marine cold-water sponge harbouring high numbers of
      microorganisms. Significant rates of nitrification have been observed in this
      sponge, indicating a substantial contribution to nitrogen turnover in marine
      environments with high sponge cover. In order to get closer insights into the
      phylogeny and function of the active microbial community and the interaction with
      its host G. barretti, a metatranscriptomic approach was employed, using the
      simultaneous analysis of rRNA and mRNA. Of the 262 298 RNA-tags obtained by
      pyrosequencing, 92% were assigned to ribosomal RNA (ribo-tags). A total of 109
      325 SSU rRNA ribo-tags revealed a detailed picture of the community, dominated by
      group SAR202 of Chloroflexi, candidate phylum Poribacteria and Acidobacteria,
      which was different in its composition from that obtained in clone libraries
      prepared form the same samples. Optimized assembly strategies allowed the
      reconstruction of full-length rRNA sequences from the short ribo-tags for more
      detailed phylogenetic studies of the dominant taxa. Cells of several phyla were
      visualized by FISH analyses for confirmation. Of the remaining 21 325 RNA-tags,
      10 023 were assigned to mRNA-tags, based on similarities to genes in the
      databases. A wide range of putative functional gene transcripts from over 10
      different phyla were identified among the bacterial mRNA-tags. The most abundant
      mRNAs were those encoding key metabolic enzymes of nitrification from ammonia
      oxidizing archaea as well as candidate genes involved in related processes. Our
      analysis demonstrates the potential and limits of using a combined rRNA and mRNA
      approach to explore the microbial community profile, phylogenetic assignments and
      metabolic activities of a complex, but little explored microbial community.

PMID- 22364355
TI  - A new luminescent terbium 4-methylsalicylate complex as a novel sensor for
      detecting the purity of methanol.
AB  - A new dinuclear terbium complex [Tb(2)(4-msal)(6)(H(2)O)(4)].6H(2)O (1) (4-msal =
      4-methylsalcylate) was synthesized. Its structure was determined by single
      crystal X-ray diffraction, and the complex was characterized by PXRD, FT-IR,
      fluorescence, TGA and DTA. Complex 1 exists as discrete molecules that are linked
      by extensive O-H ... O hydrogen bonds into a 3D network. The luminescence
      lifetimes of 3 MUM methanol solution and solid sample of 1 are 1.321 and 1.009
      ms, respectively. The quantum yield of solid sample is 6.0%. The luminescence
      quenched more than 50% when 3% (vol/vol) different impurities (acetone,
      acetonitrile, chloroform, dichloromethane, dioxane, DMF, DMSO, ethanol, ether,
      ethyl acetate, glycol, H(2)O, hexane, TEA, THF and toluene or their mixture) were
      added. The inverse linear relationship between the Lg value of fluorescence
      intensity and the volume ratio of the minor component (to a maximum of 20%) is
      interpreted in terms of LgI = a-bX (I: luminescence intensity; X: volume ratio of
      impurities in methanol; a, b are constants). So 1 is a potential luminescent
      sensor for analyzing the purity of methanol.

PMID- 22364356
TI  - Case of mucous membrane pemphigoid characterized by circulating immunoglobulin A
      and immunoglobulin G autoantibodies to the gamma-2 subunit of laminin-332.

PMID- 22364357
TI  - Base camp personnel exposure to particulate matter during wildland fire
      suppression activities.
AB  - Wildland fire base camps commonly house thousands of support personnel for weeks
      at a time. The selection of the location of these base camps is largely a
      strategic decision that incorporates many factors, one of which is the potential
      impact of biomass smoke from the nearby fire event. Biomass smoke has many
      documented adverse health effects due, primarily, to high levels of fine
      particulate matter (PM(2.5)). Minimizing particulate matter exposure to
      potentially susceptible individuals working as support personnel in the base camp
      is vital. In addition to smoke from nearby wildland fires, base camp operations
      have the potential to generate particulate matter via vehicle emissions, dust,
      and generator use. We monitored particulate matter at three base camps during the
      fire season of 2009 in Washington, Oregon, and California. During the sampling
      events, 1-min time-weighted averages of PM(2.5) and particle counts from three
      size fractions (0.3-0.5 microns, 0.5-1.0 microns, and 1.0-2.5 microns) were
      measured. Results showed that all PM size fractions (as well as overall PM(2.5)
      concentrations) were higher during the overnight hours, a trend that was
      consistent at all camps. Our results provide evidence of camp-based, site
      specific sources of PM(2.5) that could potentially exceed the contributions from
      the nearby wildfire. These exposures could adversely impact wildland firefighters
      who sleep in the camp, as well as the camp support personnel, who could include
      susceptible individuals. A better understanding of the sources and patterns of
      poor air quality within base camps would help to inform prevention strategies to
      reduce personnel exposures.

PMID- 22364354
TI  - The neural correlates of picture naming facilitated by auditory repetition.
AB  - BACKGROUND: Overt repetition of auditorily presented words can facilitate picture
      naming performance in both unimpaired speakers and individuals with word
      retrieval difficulties, but the underlying neurocognitive mechanisms and
      longevity of such effects remain unclear. This study used functional magnetic
      resonance imaging to examine whether different neurological mechanisms underlie
      short-term (within minutes) and long-term (within days) facilitation effects from
      an auditory repetition task in healthy older adults. RESULTS: The behavioral
      results showed that both short- and long-term facilitated items were named
      significantly faster than unfacilitated items, with short-term items
      significantly faster than long-term items. Neuroimaging analyses identified a
      repetition suppression effect for long-term facilitated items, relative to short
      term facilitated and unfacilitated items, in regions known to be associated with
      both semantic and phonological processing. A repetition suppression effect was
      also observed for short-term facilitated items when compared to unfacilitated
      items in a region of the inferior temporal lobe linked to semantic processing and
      object recognition, and a repetition enhancement effect when compared to long
      term facilitated items in a posterior superior temporal region associated with
      phonological processing. CONCLUSIONS: These findings suggest that different
      neurocognitive mechanisms underlie short- and long-term facilitation of picture
      naming by an auditory repetition task, reflecting both phonological and semantic
      processing. More specifically, the brain areas engaged were consistent with the
      view that long-term facilitation may be driven by a strengthening of semantic
      phonological connections. Short-term facilitation, however, appears to result in
      more efficient semantic processing and/or object recognition, possibly in
      conjunction with active recognition of the phonological form.

PMID- 22364358
TI  - The inhibitory effects of pudendal nerve stimulation on bladder overactivity in
      spinal cord injury dogs: is early stimulation necessary?
AB  - OBJECTIVE: To determine the inhibitory effects of pudendal nerve stimulation (5
      Hz) on bladder overactivity at early and late stages of spinal cord injury in
      dogs. MATERIALS AND METHODS: The study was performed in eight dogs with chronic
      spinal cord transection at the T9-T10 level. Group 1 (four dogs) underwent
      electrical stimulation of pudendal nerve one month after spinal cord transection.
      Group 2 (four dogs) underwent stimulation six months after spinal cord
      transection. The bladders were removed for histological examination of fibrosis
      after the stimulation. RESULTS: The bladder capacity and the compliance were
      significantly increased (p < 0.05) by pudendal nerve stimulation in group 1, but
      not in group 2. The nonvoiding contractions were inhibited in both groups by
      electrical stimulation. Collagen fiber was increased, while elastic fiber was
      significantly decreased (p < 0.05) in group 2 when compared with group 1.
      CONCLUSION: Pudendal nerve stimulation can increase the bladder capacity and
      compliance only during the early period before the bladder wall becomes fibrosit
      and can inhibit the nonvoiding contraction during two stages.

PMID- 22364359
TI  - "Yes, we can!": Perceptions of collective efficacy sources in volleyball.
AB  - Collective efficacy can be defined as a group's shared confidence that they will
      successfully achieve their goal. We examined which behaviours and events are
      perceived as sources of collective efficacy beliefs in a volleyball context. In
      study 1, volleyball coaches from the highest volleyball leagues (n = 33) in
      Belgium indicated the most important sources of collective efficacy. This list
      was then adapted based on the literature and on feedback given by an expert focus
      group, resulting in a 40-item questionnaire. In Study 2, coaches and players from
      all levels of volleyball in Belgium (n = 2365) rated each of these sources on
      their predictive value for collective efficacy. A principal component analysis
      revealed that the 40 sources could be divided into eight internally consistent
      factors. Positive supportive communication (e.g., enthusiasm after making a
      point) was identified as the factor most predictive for positive collective
      efficacy beliefs. The factor referring to the negative emotional reactions of
      players (e.g., discouraging body language) was the most predictive for negative
      collective efficacy beliefs. These findings offer a starting point for the design
      of continuous measurements of collective efficacy through observation.

PMID- 22364360
TI  - Controlled Sn-doping in TiO2 nanowire photoanodes with enhanced
      photoelectrochemical conversion.
AB  - We demonstrate for the first time the controlled Sn-doping in TiO(2) nanowire
      (NW) arrays for photoelectrochemical (PEC) water splitting. Because of the low
      lattice mismatch between SnO(2) and TiO(2), Sn dopants are incorporated into
      TiO(2) NWs by a one-pot hydrothermal synthesis with different ratios of SnCl(4)
      and tetrabutyl titanate, and a high acidity of the reactant solution is critical
      to control the SnCl(4) hydrolysis rate. The obtained Sn-doped TiO(2) (Sn/TiO(2))
      NWs are single crystalline with a rutile structure, and the incorporation of Sn
      in TiO(2) NWs is well controlled at a low level, that is, 1-2% of Sn/Ti ratio, to
      avoid phase separation or interface scattering. PEC measurement on Sn/TiO(2) NW
      photoanodes with different Sn doping ratios shows that the photocurrent increases
      first with increased Sn doping level to >2.0 mA/cm(2) at 0 V vs Ag/AgCl under 100
      mW/cm(2) simulated sunlight illumination up to ~100% enhancement compared to our
      best pristine TiO(2) NW photoanodes and then decreases at higher Sn doping
      levels. Subsequent annealing of Sn/TiO(2) NWs in H(2) further improves their
      photoactivity with an optimized photoconversion efficiency of ~1.2%. The incident
      photon-to-current conversion efficiency shows that the photocurrent increase is
      mainly ascribed to the enhancement of photoactivity in the UV region, and the
      electrochemical impedance measurement reveals that the density of n-type charge
      carriers can be significantly increased by the Sn doping. These Sn/TiO(2) NW
      photoanodes are highly stable in PEC conversion and thus can serve as a potential
      candidate for pure TiO(2) materials in a variety of solar energy driven
      applications.

PMID- 22364361
TI  - Hybrid nanocrystals: University of Kentucky US20060280680A1.
AB  - This patent application claims an interesting and novel combination of passive
      accumulation of drug nanocrystals within diseased tissue, in combination with
      active uptake of the nanocrystals by diseased cells. The patent application
      further claims the hybrid nanocrystals combining imaging or stabilizing molecules
      as inclusions in the crystal matrix. There is a focus on cancer chemotherapy and
      imaging, but the initial claims are not disease specific. In this patent
      evaluation, the novelty and utility of this application is examined, while the
      state of the art in nanocrystal formulations and formulation is discussed.

PMID- 22364363
TI  - Effect of incorporation of additives in tris-based egg yolk extender on buffalo
      (Bubalus bubalis) sperm tyrosine phosphorylation during cryopreservation.
AB  - Phosphorylation of tyrosine residues on sperm protein is a known indicator of
      capacitation and a major intracellular signalling event. There is evidence that
      sperm cryopreservation promotes tyrosine phosphorylation and is associated with
      reduced fertility of spermatozoa. Under this study, cryoprotective role of
      different additives namely taurine, trehalose, catalase and 4-bromophenacyl
      bromide on buffalo sperm quality was evaluated. Buffalo semen was cryopreserved
      in tris-based egg yolk extender supplemented with additives like taurine (50 mm)
      or trehalose (100 mm) or 4-bromophenacyl bromide (200 MUm) or catalase (100 U/ml)
      and used for assessment of levels of tyrosine phosphorylation in frozen-thawed
      spermatozoa. The results obtained were compared with the level of protein
      tyrosine phosphorylation of semen cryopreserved in tris-based egg yolk extender
      without additives. Proteins were extracted from a total number of nine ejaculates
      from three individual buffalo bulls chosen at random and analysed for tyrosine
      phospho-proteins using SDS-PAGE followed by immunoblotting. Monoclonal anti
      phosphotyrosine antibody (Clone pT-154) was used as primary antibody followed by
      treatment with HRP-conjugated secondary antibody. Signals were detected on X-ray
      film using chemiluminescence. Nine proteins (p20, p30, p32, p38, p49, p56, p59,
      p72 and p86) were found to be tyrosine phosphorylated in cryopreserved
      spermatozoa. Supplementation of additives significantly (p<0.05) reduced the
      level of protein tyrosine phosphorylation in spermatozoa. Moreover, this study
      showed improved (p<0.05) post-thaw motility, viability and membrane integrity of
      spermatozoa on addition of these additives. The results obtained clearly indicate
      reduced level of capacitation like changes on supplementation of additives in
      terms of protein tyrosine phosphorylation.

PMID- 22364364
TI  - Structural transformations, composition anomalies and a dramatic collapse of
      linear polymer chains in dilute ethanol-water mixtures.
AB  - Water-ethanol mixtures exhibit many interesting anomalies, such as negative
      excess partial molar volume of ethanol, excess sound absorption coefficient at
      low concentrations, and positive deviation from Raoult's law for vapor pressure,
      to mention a few. These anomalies have been attributed to different, often
      contradictory origins, but a quantitative understanding is still lacking. We show
      by computer simulation and theoretical analyses that these anomalies arise from
      the sudden emergence of a bicontinuous phase that occurs at a relatively low
      ethanol concentration of x(eth) ~ 0.06-0.10 (that amounts to a volume fraction of
      0.17-0.26, which is a significant range!). The bicontinuous phase is formed by
      aggregation of ethanol molecules, resulting in a weak phase transition whose
      nature is elucidated. We find that the microheterogeneous structure of the
      mixture gives rise to a pronounced nonmonotonic composition dependence of local
      compressibility and nonmonotonic dependence in the peak value of the radial
      distribution function of ethyl groups. A multidimensional free energy surface of
      pair association is shown to provide a molecular explanation of the known
      negative excess partial volume of ethanol in terms of parallel orientation and
      hence better packing of the ethyl groups in the mixture due to hydrophobic
      interactions. The energy distribution of the ethanol molecules indicates
      additional energy decay channels that explain the excess sound attenuation
      coefficient in aqueous alcohol mixtures. We studied the dependence of the
      solvation of a linear polymer chain on the composition of the water-ethanol
      solvent. We find that there is a sudden collapse of the polymer at x(eth) ~ 0.05
      a phenomenon which we attribute to the formation of the microheterogeneous
      structures in the binary mixture at low ethanol concentrations. Together with
      recent single molecule pulling experiments, these results provide new insight
      into the behavior of polymer chain and foreign solutes, such as enzymes, in
      aqueous binary mixtures.

PMID- 22364366
TI  - Factors predicting early- and long-term survival in patients undergoing
      extracorporeal membrane oxygenation (ECMO).
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an established
      treatment option in patients with cardiogenic shock and respiratory dysfunction.
      We assessed outcomes of ECMO, as well as predictors of ECMO weaning and survival,
      in patients treated in our institution over the past five years. METHODS: We
      reviewed the records of 185 patients who received ECMO support for various
      medical conditions between January 2005 and January 2010. Risk factors for
      successful weaning, early mortality, and overall survival were investigated.
      RESULTS: There were 101 males and 84 females, and the mean age was 56.1 +/- 14.7
      years. Patients received either venoarterial (n = 137) or veno-veno (n = 48)
      ECMO. ECMO was instituted in stable patients (n = 40, 21.6%), those in shock (n =
      105, 56.8%), or those in cardiac arrest (n = 40, 21.6%). Mean ECMO support lasted
      4.7 days and weaning was successful in 68 patients (36.7%), with 38 (20.5%)
      eventually being discharged from the hospital. Univariate analysis showed
      hemodynamic status at insertion (p = 0.05) including intra-aortic balloon pump
      usage to significantly influence successful weaning, whereas the duration of ECMO
      was strongly associated with overall survival (p = 0.05). CONCLUSIONS: Early ECMO
      application before catastrophic clinical deterioration and weaning as soon as
      possible may enhance overall survival.

PMID- 22364368
TI  - The mechanics of bacterial cluster formation on plant leaf surfaces as revealed
      by bioreporter technology.
AB  - Bacteria that colonize the leaves of terrestrial plants often occur in clusters
      whose size varies from a few to thousands of cells. For the formation of such
      bacterial clusters, two non-mutually exclusive but very different mechanisms may
      be proposed: aggregation of multiple cells or clonal reproduction of a single
      cell. Here we assessed the contribution of both mechanisms on the leaves of bean
      plants that were colonized by the bacterium Pantoea agglomerans. In one approach,
      we used a mixture of green and red fluorescent P. agglomerans cells to populate
      bean leaves. We observed that this resulted in clusters made up of only one
      colour as well as two-colour clusters, thus providing evidence for both
      mechanisms. Another P. agglomerans bioreporter, designed to quantify the
      reproductive success of bacterial colonizers by proxy to the rate at which green
      fluorescent protein is diluted from dividing cells, revealed that during the
      first hours on the leaf surface, many bacteria were dividing, but not staying
      together and forming clusters, which is suggestive of bacterial relocation.
      Together, these findings support a dynamic model of leaf surface colonization,
      where both aggregative and reproductive mechanisms take place. The bioreporter
      based approach we employed here should be broadly applicable towards a more
      quantitative and mechanistic understanding of bacterial colonization of surfaces
      in general.

PMID- 22364367
TI  - Feasibility study of a clinically-integrated randomized trial of modifications to
      radical prostatectomy.
AB  - BACKGROUND: Numerous technical modifications to radical prostatectomy have been
      proposed. Such modifications are likely to lead to only slight improvements in
      outcomes. Although small differences would be worthwhile, an appropriately
      powered randomized trial would need to be very large, and thus of doubtful
      feasibility given the expense, complexity and regulatory burden of contemporary
      clinical trials. We have proposed a novel methodology, the clinically-integrated
      randomized trial, which dramatically streamlines trial procedures in order to
      reduce the marginal cost of an additional patient towards zero. We aimed to
      determine the feasibility of implementing such a trial for radical prostatectomy.
      METHODS: Patients undergoing radical prostatectomy as initial treatment for
      prostate cancer were randomized in a factorial design to involvement of the
      fascia during placement of the anastomotic sutures, urethral irrigation, both or
      neither. Endpoint data were obtained from routine clinical documentation. Accrual
      and compliance rates were monitored to determine the feasibility of the trial.
      RESULTS: From a total of 260 eligible patients, 154 (59%) consented; 56 patients
      declined to participate, 20 were not approached on recommendation of the treating
      surgeon, and 30 were not approached for logistical reasons. Although recording by
      surgeons of the procedure used was incomplete (~80%), compliance with
      randomization was excellent when it was recorded, with only 6% of procedures
      inconsistent with allocation. Outcomes data was received from 71% of patients at
      one year. This improved to 83% as the trial progressed. CONCLUSIONS: A clinically
      integrated randomized trial was conducted at low cost, with excellent accrual,
      and acceptable compliance with treatment allocation and outcomes reporting. This
      demonstrates the feasibility of the methodology. Improved methods to ensure
      documentation of surgical procedures would be required before wider
      implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00928850.

PMID- 22364369
TI  - Cyclopentadiene based low-valent group 13 metal compounds: ligands in
      coordination chemistry and link between metal rich molecules and intermetallic
      materials.

PMID- 22364370
TI  - Inflammatory disseminated superficial porokeratosis with an unusual clinical
      feature of the pruritic, erythematous papules preceding annular brownish
      pigmentation.

PMID- 22364371
TI  - Effects of labeling on preschoolers' explicit false belief performance: outcomes
      of cognitive flexibility or inhibitory control?
AB  - Executive function mechanisms underpinning language-related effects on theory of
      mind understanding were examined in a sample of 165 preschoolers. Verbal labels
      were manipulated to identify relevant perspectives on an explicit false belief
      task. In Experiment 1 with 4-year-olds (N = 74), false belief reasoning was
      superior in the fully and protagonist-perspective labeled conditions compared to
      the child-perspective and nondescript labeling conditions. In Experiment 2 with 3
      year-olds (N = 53), labeling the nondominant belief only biased attentional
      inertia. In Experiment 3 testing generalization in 4-year-olds (N = 38), labeling
      manipulations translated to improved performance on a second label-free explicit
      false belief task. These outcomes fit a cognitive flexibility account whereby age
      changes in the effects of labeling turn on formulating sophisticated conceptual
      representations.

PMID- 22364372
TI  - Two-body wear of monolithic, veneered and glazed zirconia and their corresponding
      enamel antagonists.
AB  - OBJECTIVE: This study tested whether the two-body wear of monolithic zirconia and
      their corresponding enamel antagonists was higher compared to monolithic alloy
      and veneered zirconia. MATERIALS AND METHODS: Cylindrical specimens (N = 36, n =
      6) were prepared out of (A) veneered zirconia (VZ), (B) glazed zirconia using a
      glaze ceramic (GZC), (C) glazed zirconia using a glaze spray (GZS), (D) manually
      polished monolithic zirconia (MAZ), (E) mechanically polished monolithic zirconia
      (MEZ) and (F) monolithic base alloy (control group, MA). Wear tests were
      performed in a chewing simulator (49 N, 1.7 Hz, 5 degrees C/50 degrees C) with
      enamel antagonists. The wear analysis was performed using a 3D profilometer
      before and after 120,000, 240,000, 640,000 and 1,200,000 masticatory cycles. SEM
      images were used for evaluating wear qualitatively. The longitudinal results were
      analysed using linear mixed models (alpha = 0.05). RESULTS: Materials (p < 0.001)
      and number of masticatory cycles (p < 0.001) had a significant effect on the wear
      level. The least enamel antagonist wear was observed for MAZ and MEZ (27.3 +/-
      15.2, 28 +/- 11.1 MUm, respectively). GZC (118 +/- 30.9 MUm) showed the highest
      wear of enamel antagonists. The highest wear rate in the material was observed in
      GZS (91.3 +/- 38.6 MUm). While in the groups of MA, VZ, GZC and GZS 50% of the
      specimens developed cracks in enamel, it was 100% in MAZ and MEZ groups.
      CONCLUSION: Polished monolithic zirconia showed lower wear rate on enamel
      antagonists as well as within the material itself but developed higher rates of
      enamel cracks.

PMID- 22364373
TI  - Systems biology-based approaches toward understanding drought tolerance in food
      crops.
AB  - Economically important crops, such as maize, wheat, rice, barley, and other food
      crops are affected by even small changes in water potential at important growth
      stages. Developing a comprehensive understanding of host response to drought
      requires a global view of the complex mechanisms involved. Research on drought
      tolerance has generally been conducted using discipline-specific approaches.
      However, plant stress response is complex and interlinked to a point where
      discipline-specific approaches do not give a complete global analysis of all the
      interlinked mechanisms. Systems biology perspective is needed to understand
      genome-scale networks required for building long-lasting drought resistance.
      Network maps have been constructed by integrating multiple functional genomics
      data with both model plants, such as Arabidopsis thaliana, Lotus japonicus, and
      Medicago truncatula, and various food crops, such as rice and soybean. Useful
      functional genomics data have been obtained from genome-wide comparative
      transcriptome and proteome analyses of drought responses from different crops.
      This integrative approach used by many groups has led to identification of
      commonly regulated signaling pathways and genes following exposure to drought.
      Combination of functional genomics and systems biology is very useful for
      comparative analysis of other food crops and has the ability to develop stable
      food systems worldwide. In addition, studying desiccation tolerance in
      resurrection plants will unravel how combination of molecular genetic and
      metabolic processes interacts to produce a resurrection phenotype. Systems
      biology-based approaches have helped in understanding how these individual
      factors and mechanisms (biochemical, molecular, and metabolic) "interact"
      spatially and temporally. Signaling network maps of such interactions are needed
      that can be used to design better engineering strategies for improving drought
      tolerance of important crop species.

PMID- 22364374
TI  - Does extensive on-water rowing increase muscular strength and endurance?
AB  - The purpose of this study was to compare changes in aerobic condition, strength,
      and muscular endurance following 8 weeks of endurance rowing alone or in
      combination with weight-training. Twenty-two elite rowers were assigned to (1)
      rowing (n = 10, 250-270 km . week-1) or (2) rowing (n = 12, 190-210 km . week-1)
      plus four weight-training sessions each week. Pre and post mean and standardized
      effect-size (ES) differences in aerobic condition (watts at 4 mmol . L-1) and
      strength (isometric pull, N), prone bench-pull (6-repetition maximum, 6-RM), 5-
      and 30-repetition leg-press and 60-repetition seated-arm-pull (J, performed on a
      dynamometer) normalized by body mass and log-transformed were analysed, after
      adjusting for gender. The standardized differences between groups were trivial
      for aerobic condition (ES [+/-90% CI] = 0.15; +/-0.28, P = 0.37) and prone bench
      pull (ES = 0.27; +/-0.33, P = 0.18), although a moderate positive benefit in
      favour of rowing only was observed for the seated-arm-pull (ES = 0.42; +/-0.4, P
      = 0.08). Only the weight-training group improved isometric pull (12.4 +/- 8.9%, P
      < 0.01), 5-repetition (4.0 +/- 5.7%, P < 0.01) and 30-repetition (2.4 +/- 5.4%, P
      < 0.01) leg-press. In conclusion, while gains in aerobic condition and upper-body
      strength were comparable to extensive endurance rowing, weight-training led to
      moderately greater lower-body muscular-endurance and strength gains.

PMID- 22364375
TI  - Isokinetic hamstrings-to-quadriceps peak torque ratio: the influence of sport
      modality, gender, and angular velocity.
AB  - The purpose of this study was to determine differences in hamstrings-to
      quadriceps (H/Q) peak torque ratios evaluated at different angular velocities
      between men and women who participate in judo, handball or soccer. A total of 166
      athletes, including 58 judokas (26 females and 32 males), 39 handball players (22
      females and 17 males), and 69 soccer players (17 females and 52 males), were
      evaluated using an isokinetic dynamometer. The H/Q isokinetic peak torque ratios
      were calculated at angular velocities of 1.05 rad . s-1 and 5.23 rad . s-1. In
      the analysis by gender, female soccer players produced lower H/Q peak torque
      ratios at 1.05 rad . s-1 than males involved in the same sport. However, when H/Q
      peak torque ratio was assessed at 5.23 rad . s-1, there were no significant
      differences between the sexes. In the analysis by sport, there were no
      differences among females at 1.05 rad . s-1. In contrast, male soccer players had
      significantly higher H/Q peak torque ratios than judokas (66 +/- 12% vs. 57 +/-
      14%, respectively). Female handball players produced significantly lower peak
      torque ratios at 5.23 rad . s-1 than judokas or soccer players, whereas males
      presented no ratio differences among sports At 5.23 rad . s-1. In the analysis by
      velocity, women's muscular ratios assessed at 1.05 rad . s-1 were significantly
      lower than at 5.23 rad . s-1 for all sports; among men, only judokas presented
      lower ratios at 1.05 rad . s-1 than at 5.23 rad . s-1. The present results
      suggest that sport modality and angular velocity influence the isokinetic
      strength profiles of men and women.

PMID- 22364376
TI  - Prediction of maximal lactate steady state in runners with an incremental test on
      the field.
AB  - During a maximal incremental ergocycle test, the power output associated with
      Respiratory Exchange Ratio equal to 1.00 (RER = 1.00) predicts maximal lactate
      steady state (MLSS). We hypothesised that these results are transferable for
      runners on the field. Fourteen runners performed a maximal progressive test, to
      assess the speed associated with RER = 1.00, and several 30 minutes constant
      velocity tests to determine the speed at MLSS. We observed that the speeds at RER
      = 1.00, at the second ventilatory threshold (VT2) and at MLSS did not differ
      (15.7 +/- 1.1 km . h-1, 16.2 +/- 1.4 km . h-1, 15.5 +/- 1.1 km . h-1
      respectively). The speed associated with RER = 1.00 was better correlated with
      that at MLSS (r = 0.79; p = 0.0008) than that at VT2 (r = 0.73; p = 0.002).
      Neither the concentration of blood lactate nor the heart rate differed between
      the speed at RER = 1.00 and that at MLSS from the 10th and the 30th minute of the
      constant velocity test. Bland and Altman analysis showed a fair agreement between
      the speed at MLSS and that at RER (0.2 +/- 1.4 km . h-1). This study demonstrated
      that the speed associated with RER = 1.00 determined during maximal progressive
      track running allows a fair estimation of the speed associated with MLSS,
      markedly decreasing the burden of numerous invasive tests required to assess it.

PMID- 22364377
TI  - Radical prostatectomy in very high-risk localized prostate cancer: long-term
      outcomes and outcome predictors.
AB  - OBJECTIVE: The objective of this study was to present the long-term outcomes and
      determine outcome predictors in very high-risk (cT3b-T4) prostate cancer (PCa)
      after radical prostatectomy (RP). MATERIAL AND METHODS: Between January 1989 and
      December 2004, 51 patients with cT3b-T4 PCa underwent RP. Kaplan-Meier survival
      analysis was used to calculate the biochemical progression-free survival (BPFS),
      clinical progression-free survival (CPFS), cancer-specific survival (CSS) and
      overall survival (OS) rate. Multivariate Cox proportional hazard models were used
      to determine the predictive power of clinical and pathological variables in BPFS
      and CPFS. RESULTS: Median follow-up was 108 months [interquartile range (IQR)
      73.5-144.5]. The median serum prostate-specific antigen (PSA) was 16.9 ng/ml (IQR
      7-37.2). Median biopsy and pathological Gleason (pGS) score were both scored as 7
      (range 4-10 and 5-9, respectively). Overstaging was frequent (37.2%); four
      patients (7.8%) had organ-confined stage pT2, while 15 (29.4%) had extracapsular
      extension only (pT3a). Another 23 (45.1%) were confirmed with seminal vesicle
      invasion (pT3b) and nine (17.7%) had adjacent structure invasion (pT4). Eleven
      patients (21.6%) had lymph-node involvement. Thirty-two patients (62.7%) had
      positive surgical margins. The BPFS, CPFS, CSS and OS at 5 and 10 years were
      52.7%, 45.8%;78.0%, 72.5%; 91.9%, 91.9% and 88.0%, 70.7%. In the multivariate Cox
      proportional hazard models, pathological stage was an independent predictor of
      BPFS while preoperative PSA and pGS was an independent predictor of CPFS.
      CONCLUSIONS: The management of cT3b-T4 PCa typically consists of a multimodality
      treatment in which RP is a valuable first step. Overstaging was frequent (37.2%),
      and almost one-quarter of the patients remained free of additional treatments.
      Long-term cancer-related outcomes were very satisfactory.

PMID- 22364379
TI  - N-Acetylcysteine supplementation for the prevention of atrial fibrillation after
      cardiac surgery: a meta-analysis of eight randomized controlled trials.
AB  - BACKGROUND: Atrial fibrillation is the most common type of arrhythmia after
      cardiac surgery. An increasing body of evidence demonstrates that oxidative
      stress plays a pivotal role in the pathophysiology of atrial fibrillation. N
      acetylcysteine (NAC) is a free radical scavenger, and may attenuate this
      pathophysiologic response and reduce the incidence of postoperative AF (POAF).
      However, it is unclear whether NAC could effectively prevent POAF. Therefore,
      this meta-analysis aims to assess the efficacy of NAC supplementation on the
      prevention of POAF. METHODS: Medline and Embase were systematically reviewed for
      studies published up to November 2011, in which NAC was compared with controls
      for adult patients undergoing cardiac surgery. Outcome measures comprised the
      incidence of POAF and hospital length of stay (LOS). The meta-analysis was
      performed with the fixed-effect model or random-effect model according to the
      heterogeneity. RESULTS: Eight randomized trials incorporating 578 patients
      provided the best evidence and were included in this meta-analysis. NAC
      supplementation significantly reduced the incidence of POAF (OR 0.62, 95% CI 0.41
      to 0.93; P = 0.021) compared with controls, but had no effect on LOS (WMD -0.07,
      95% CI -0.42 to 0.28; P = 0.703). CONCLUSIONS: The prophylactic NAC
      supplementation may effectively reduce the incidence of POAF. However, the
      overall quality of current studies is poor and further research should focus on
      adequately powered randomized controlled trials with POAF incidence as a primary
      outcome measure.

PMID- 22364382
TI  - Topographic and spectroscopic characterization of electronic edge states in CVD
      grown graphene nanoribbons.
AB  - We used scanning tunneling microscopy and spectroscopy (STM/S) techniques to
      analyze the relationships between the edge shapes and the electronic structures
      in as-grown chemical vapor deposition (CVD) graphene nanoribbons (GNRs). A rich
      variety of single-layered graphene nanoribbons exhibiting a width of several to
      100 nm and up to 1 MUm long were studied. High-resolution STM images highlight
      highly crystalline nanoribbon structures with well-defined and clean edges.
      Theoretical calculations indicate clear spin-split edge states induced by
      electron-electron Coulomb repulsion. The edge defects can significantly modify
      these edge states, and different edge structures for both sides of a single
      ribbon produce asymmetric electronic edge states, which reflect the more
      realistic features of CVD grown GNRs. Three structural models are proposed and
      analyzed to explain the observations. By comparing the models with an atomic
      resolution image at the edge, a pristine (2,1) structure was ruled out in favor
      of a reconstructed edge structure composed of 5-7 member rings, showing a better
      match with experimental results, and thereby suggesting the possibility of a
      defective morphology at the edge of CVD grown nanoribbons.

PMID- 22364381
TI  - Gadolinium containing photochromic micelles as potential magnetic resonance
      imaging traceable drug carriers.
AB  - Novel photochromic amphipathic molecules, KMR-AZn (Gd-DTPA-AZCn), composed of
      hydrophilic Gd-DTPA and hydrophobic alkylated azobenzene were prepared. In
      aqueous environment, KMR-AZn indicated self-assembly. The resulting aggregates
      were demonstrated to be able to include a hydrophobic drug substitute
      (hydrophobic fluorescent dye) into the internal core, and to release the included
      compound upon photoirradiation within 10 min through the influence of azobenzene
      photoisomerization. This micellar MRI contrast agent exhibited three- to four
      fold higher r(1) relaxivity (r(1) = 14.5-16.5 mM(-1) s(-1), 0.47 T at 40 degrees
      C) than the widely applied small molecule contrast agent Gd-DTPA (Magnevist((r))
      r(1)  = 4.1 mM(-1) s(-1), 0.47 T at 40 degrees C). This dual functionality of
      encapsulated compound release and increased MR imaging contrast indicates that
      KMR-AZn is a potential candidate for application as a lipid-based MRI-traceable
      drug carrier.

PMID- 22364383
TI  - Meta-analysis of randomized controlled trials on the treatment of unprotected
      left main coronary artery disease: one-year outcomes with coronary artery bypass
      grafting versus percutaneous coronary artery intervention with drug-eluting
      stent.
AB  - BACKGROUND AND AIM: Coronary artery bypass surgery (CABG) is the standard
      treatment for left main coronary artery (LMCA) disease. However, percutaneous
      coronary intervention using drug-eluting stents (DES-PCI) is now widely used and
      is associated with improved outcomes following coronary revascularization. The
      goal of this study was to assess early outcomes associated with CABG and DES-PCI
      among patients with LMCA disease through a meta-analysis of randomized controlled
      trials. METHODS AND RESULTS: After searching of electronic databases, three
      randomized controlled trials with 2601 patients were identified. All-cause death
      occurred in 3.3% with CABG and 3.6% with DES-PCI (odds ratio [OR], 0.92; 95%
      confidence interval [CI]= 0.60 to 1.40; p = 0.76). The incidence of myocardial
      infarction was 2.6% with CABG and 3.8% with DES-PCI (OR, 0.67; 95% CI = 0.43 to
      1.05; p = 0.10). Target vessel revascularization occurred in 5.1% with CABG and
      11.7% with DES-PCI (OR, 0.40; 95% CI = 0.29 to 0.55; p < 0.0001). Major adverse
      cardiac and cerebrovascular events (MACCE) occurred in 10.7% with CABG and 15.7%
      with DES-PCI (OR, 0.40; 95% CI = 0.29 to 0.55; p < 0.0001). CONCLUSIONS: DES-PCI
      is a safe alternative to CABG for the management of LMCA disease. However, CABG
      was superior to DES-PCI in terms of MACCE and need for target vessel
      revascularization at one year. Thus, CABG remains the standard of care for the
      treatment of LMCA disease.

PMID- 22364384
TI  - Effect of education and health locus of control on safe use of pesticides: a
      cross sectional random study.
AB  - BACKGROUND: In Egypt, many pesticides are used to control pests in agricultural
      farms. Our study aimed to investigate knowledge and behaviors of farmers related
      to pesticide use and their relation to educational level and health locus of
      control. Health locus of control is the degree to which individuals believe that
      their health is controlled by internal or external factors. METHODS: A cross
      sectional randomized approach was used to collect data from 335 farmers in
      Mahmoudiya region, Egypt using an interview questionnaire. Results were analyzed
      using Pearson Chi-square test, Fisher's exact test, Student t-test and ANOVA.
      RESULTS: The average age of farmers was 34 years and 61% of them didn't receive
      school education. School education was related to higher levels of knowledge and
      behaviors. Farmers who received school education had more knowledge about the
      negative effects of pesticides on health and routes of contamination with
      pesticides. They also had higher scores on reading labels of pesticides
      containers and taking precautions after coming in contact with pesticides.
      Regarding health locus of control, higher internal beliefs were significantly
      related to higher knowledge and behaviors scores, while there was no significant
      relation between chance and powerful others beliefs with knowledge or behaviors.
      CONCLUSION: In the present study, higher level of education and lower level of
      internal beliefs were related to better knowledge and safer use of pesticides
      among Egyptian farmers. We recommend that strategies for raising internal beliefs
      must be included in health education programs that aim to ameliorate pesticides
      use among farmers.

PMID- 22364385
TI  - Acral junctional nevus with prominent pagetoid spread.

PMID- 22364386
TI  - Protonation and anion binding control the kinetics of iron release from human
      transferrin.
AB  - Iron release in vitro from human serum diferric transferrin (hFe(2)Tf) in acidic
      media (4.2 <= pH <= 5.4) in the presence of nonsynergistic anions occurs in at
      least five kinetic steps. Step 1 (most rapid) involves proton assisted release of
      carbonate from the protein. In subsequent steps, iron release from both the N-
      and C-terminal lobes is controlled by slow proton transfers and anion binding. In
      step 2, the N-terminal lobe takes up one proton with kinetic linkage to the
      binding of one anion. In step 3, iron release from the anion-linked N-terminal
      lobe is controlled by slow uptake of two protons with rate-constant, k(2N), of
      2.6(6) * 10(7), 6.1(6) * 10(7), and 9(1) * 10(7) M(-2) s(-1) in the presence of
      Cl(-), NO(3)(-), and SO(4)(2-), respectively. In step 4, the C-terminal lobe
      takes up one proton with kinetic linkage to the binding of one anion. In step 5,
      iron release from the anion-linked C-terminal lobe is controlled by slow uptake
      of two protons with rate-constant, k(2C), of 8.4(2) * 10(4), 4.4(6) * 10(5), and
      8.1(2) * 10(5) M(-2) s(-1) in the presence of Cl(-), NO(3)(-), and SO(4)(2-),
      respectively.

PMID- 22364387
TI  - Does regular exercise during pregnancy influence lumbopelvic pain? A randomized
      controlled trial.
AB  - OBJECTIVE: To study lumbopelvic pain in women randomized to a regular exercise
      program during pregnancy in comparison to women receiving standard antenatal
      care. DESIGN: A two-armed, two-center, randomized controlled trial. Setting. St
      Olavs Hospital, Trondheim University Hospital and Stavanger University Hospital.
      POPULATION: A total of 855 pregnant women were randomized to intervention or
      control groups. METHODS: The intervention was a 12 week exercise program,
      including aerobic and strengthening exercises, conducted between 20 and 36 weeks
      of pregnancy. One weekly group session was led by physiotherapists, and home
      exercises were encouraged twice a week. The control group received standard
      antenatal care. MAIN OUTCOME MEASURES: Self-reports of lumbopelvic pain and sick
      leave due to lumbopelvic pain. The data were analysed according to the "intention
      to-treat" principle. RESULTS: There were no significant differences between
      groups of women reporting lumbopelvic pain at 36 weeks (74 vs. 75%, p=0.76). The
      proportion of women on sick leave due to lumbopelvic pain was lower in the
      intervention group (22% vs 31%, p=0.01). CONCLUSIONS: Exercise during pregnancy
      does not influence the prevalence of lumbopelvic pain, but women offered a
      regular exercise course seem to handle the disorder better.

PMID- 22364388
TI  - Managing glaucoma in those with co-morbidity: not as easy as it seems.
AB  - PURPOSE: To identify the extent of use of medicines recommended to be used with
      caution in glaucoma patients with specified comorbidities and to determine
      evidence of associated harm. Retrospective cohort analysis from administrative
      claims data and prescription/event sequence symmetry analysis. PARTICIPANTS:
      Australian Government Department of Veterans' Affairs treatment card holders
      dispensed glaucoma eye-drops. MAIN OUTCOME MEASURES: Proportion of veterans with
      glaucoma and diabetes, airways disease, heart failure, ischemic heart disease or
      depression, dispensed glaucoma eye drops which should be used with caution. For
      harms, outcome measures were hospitalizations for airways disease and heart
      disease. RESULTS: The cohort analysis included 25,984 veterans. Of these, 88%
      with airways disease were dispensed glaucoma eye drops with the potential to
      aggravate airways disease, 43% with heart failure were dispensed topical beta
      blockers and 49% with depression received glaucoma eye drops which should be used
      cautiously in those with depression. We found increased risk of initiation of
      inhaled beta-agonist following timolol (adjusted sequence ratio (ASR) 1.48, 99%
      CI 1.22-1.78) and latanoprost (ASR 1.24, 99% CI 1.11-1.38) initiation. We found
      increased risk of inhaled corticosteroid initiation following initiation of
      timolol (ASR 1.43, 99% CI 1.13-1.81). There was increased risk of antidepressant
      initiation following timolol initiation (ASR 1.24, 99% CI 1.07-1.43), and
      latanoprost (ASR 1.16, 99% CI 1.03-1.31). There was also increased risk of
      hospitalization for bradycardia following timolol initiation (ASR 2.22,99% CI
      1.15-4.31). CONCLUSION: Use of glaucoma eye drops recommended to be used with
      caution in co-morbidities is common and was associated with adverse outcomes.
      Awareness of co-morbidities is required in the selection and prescription of
      glaucoma eye drops.

PMID- 22364390
TI  - Adjustable continence balloons: clinical results of a new minimally invasive
      treatment for male urinary incontinence.
AB  - OBJECTIVE: This study aimed to evaluate the results of the Danish experience with
      the ProACT urinary continence device inserted in men with stress urinary
      incontinence. MATERIAL AND METHODS: The ProACT was inserted in 114 patients. Data
      were registered prospectively. The main endpoints were complications, pad use per
      day and 24 h urinary leakage. A questionnaire evaluating symptoms and
      satisfaction was sent to the patients. RESULTS: Data including preoperative and
      postoperative pad use and urinary leakage were available for 92 and 90 patients,
      respectively. A decrease in the median 24 h urinary leakage (352.5 vs 11 ml, p <
      0.001) and in the median number of pads used per day (4.75 vs 2.25, p = 0.001)
      was demonstrated. Forty-six patients had a pad use of 0-1 pads per day and/or a
      daily urinary leakage less than 8 g, corresponding to an overall dry rate of 50%.
      A decrease in urinary leakage > 50% was seen in 72 patients (80%). Complications
      were seen in 23 patients. All of these were treated successfully by removal of
      the device in the outpatient setting followed by replacement of the device.
      Another eight patients had a third balloon inserted to improve continence
      further. Fourteen patients (12%) ended up with an artificial sphincter or a
      urethral sling. Sixty patients (63%) experienced no discomfort and 58 (61%)
      reported being dry or markedly improved. Overall, 50 patients (53%) reported
      being very or predominantly satisfied. CONCLUSIONS: Adjustable continence
      balloons seem to be a good alternative in the treatment of male urinary
      incontinence. Complications are mild and easily treated.

PMID- 22364389
TI  - Laforin, a protein with many faces: glucan phosphatase, adapter protein, et alii.
AB  - Lafora disease (LD) is a rare, fatal neurodegenerative disorder characterized by
      the accumulation of glycogen-like inclusions in the cytoplasm of cells from most
      tissues of affected patients. One hundred years after the first description of
      these inclusions, the molecular bases underlying the processes involved in LD
      physiopathology are finally being elucidated. The main cause of the disease is
      related to the activity of two proteins, the dual-specificity phosphatase laforin
      and the E3-ubiquitin ligase malin, which form a functional complex. Laforin is
      unique in humans, as it is composed of a carbohydrate-binding module attached to
      a cysteine-based catalytic dual-specificity phosphatase domain. Laforin directly
      dephosphorylates glycogen, but other proteinaceous substrates, if they exist,
      have remained elusive. Recently, an emerging set of laforin-binding partners
      apart from malin have been described, suggestive of laforin roles unrelated to
      its catalytic activity. Further investigations based on different transgenic
      mouse models have shown that the laforin-malin complex is also involved in other
      cellular processes, such as response to endoplasmic reticulum stress and
      misfolded protein clearance by the lysosomal pathway. However, controversial data
      and some missing links still make it difficult to assess the concrete
      relationship between glycogen deregulation and neuronal damage leading to the
      fatal symptoms observed in LD patients, such as myoclonic seizures and epilepsy.
      Consequently, clinical treatments are far from being achieved. In the present
      review, we focus on the knowledge of laforin biology, not only as a glucan
      phosphatase, but also as an adaptor protein involved in several physiological
      pathways.

PMID- 22364392
TI  - The chemistry of N-hydroxyamidoximes, N-aminoamidoximes, and hydrazidines.

PMID- 22364391
TI  - The combined effect of the T2DM susceptibility genes is an important risk factor
      for T2DM in non-obese Japanese: a population based case-control study.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic
      disorder. Recently, several genome-wide association studies (GWAS) have
      identified many novel susceptibility loci for T2DM, and indicated that there are
      common genetic causes contributing to the susceptibility to T2DM in multiple
      populations worldwide. In addition, clinical and epidemiological studies have
      indicated that obesity is a major risk factor for T2DM. However, the prevalence
      of obesity varies among the various ethnic groups. We aimed to determine the
      combined effects of these susceptibility loci and obesity/overweight for
      development of T2DM in the Japanese. METHODS: Single nucleotide polymorphisms
      (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in
      Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417
      control subjects. RESULTS: We confirmed that the cumulative number of risk
      alleles based on 17 susceptibility loci for T2DM was an important risk factor in
      the development of T2DM in Japanese population (P<0.0001), although the effect of
      each risk allele was relatively small. In addition, the significant association
      between an increased number of risk alleles and an increased risk of T2DM was
      observed in the non-obese group (P<0.0001 for trend), but not in the
      obese/overweight group (P=0.88 for trend). CONCLUSIONS: Our findings indicate
      that there is an etiological heterogeneity of T2DM between obese/overweight and
      non-obese subjects.

PMID- 22364394
TI  - High prevalence of risk factors for chronic kidney disease in Balkan endemic
      nephropathy foci.
AB  - BACKGROUND/AIMS: The aim of this study was to find out the prevalence of the most
      frequent risk factors for chronic kidney disease (CKD) and the prevalence of
      urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy
      (BEN) villages near Bijeljina, Bosnia and Herzegovina. METHODS: The survey
      consisted of an interview, blood pressure measurement, and urine dipstick test
      for proteinuria, hematuria, and glycosuria. RESULTS: The study involved 1625 (739
      males, aged 51 +/- 16 years) subjects: 319 (19.6%) with positive family history
      for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with
      diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was
      present in 6.2-7.1% of the subjects with risk factors for CKD but in 3.4% of
      those without risk factors. Systolic blood pressure and BEN in brother/sister
      were found to be significant variables associated with proteinuria, but female
      gender and history of kidney disease with hematuria. CONCLUSION: In addition to a
      family burden for BEN, other risk factors for CKD were highly prevalent in BEN
      villages of the Bijeljina municipality. The frequency of proteinuria was higher
      in the at-risk group than in the group without risk factors and increased with
      the number of risk factors.

PMID- 22364395
TI  - The effects of auditory information on 4-month-old infants' perception of
      trajectory continuity.
AB  - Young infants perceive an object's trajectory as continuous across occlusion
      provided the temporal or spatial gap in perception is small. In 3 experiments
      involving 72 participants the authors investigated the effects of different forms
      of auditory information on 4-month-olds' perception of trajectory continuity.
      Provision of dynamic auditory information about the object's trajectory enhanced
      perception of trajectory continuity. However, a smaller positive effect was also
      obtained when the sound was continuous but provided no information about the
      object's location. Finally, providing discontinuous auditory information or
      auditory information that was dislocated relative to vision had negative effects
      on trajectory perception. These results are discussed relative to the
      intersensory redundancy hypothesis and emphasize the need to take an intersensory
      approach to infant perception.

PMID- 22364396
TI  - Visualization and quantitative analysis of G protein-coupled receptor-beta
      arrestin interaction in single cells and specific organs of living mice using
      split luciferase complementation.
AB  - Methods used to assess the efficacy of potentially therapeutic reagents for G
      protein-coupled receptors (GPCRs) have been developed. Previously, we
      demonstrated sensitive detection of the interaction of GPCRs and beta-arrestin2
      (ARRB2) using 96-well microtiter plates and a bioluminescence microscope based on
      split click beetle luciferase complementation. Herein, using firefly luciferase
      emitting longer wavelength light, we demonstrate quantitative analysis of the
      interaction of beta2-adrenergic receptor (ADRB2), a kind of GPCR, and ARRB2 in a
      96-well plate assay with single-cell imaging. Additionally, we showed
      bioluminescence in vivo imaging of the ADRB2-ARRB2 interaction in two systems:
      cell implantation and hydrodynamic tail vein (HTV) methods. Specifically, in the
      HTV method, the luminescence signal from the liver upon stimulation of an agonist
      for ADRB2 was obtained in the intact systems of mice. The results demonstrate
      that this method enables noninvasive screening of the efficacy of chemicals at
      the specific organ in in vivo testing. This in vivo system can contribute to
      effective evaluation in pharmacokinetics and pharmacodynamics and expedite the
      development of new drugs for GPCRs.

PMID- 22364397
TI  - Theoretical study of absorption and fluorescence spectra of firefly luciferin in
      aqueous solutions.
AB  - The absorption and fluorescence spectra of firefly luciferin, which is an analog
      of oxyluciferin, are investigated by performing the density functional theory
      (DFT) calculations, especially focusing on the experimentally unassigned peaks.
      Time-dependent DFT calculations are performed for the excited states of firefly
      luciferin and its conjugate acids and bases. We find that (1) the peaks in the
      experimental absorption spectra correspond to the excited states of not only
      (6'O(-), 4COO(-)) and (6'OH, 4COO(-)), but also (6'OH, 4COOH) and (6'OH, 3H(+),
      4COOH); (2) the peaks in the experimental fluorescence spectra correspond to the
      excited states of not only (6'O(-), 4COO(-)), but also (6'OH, 4COO(-)), (6'O(-),
      4COOH), (6'OH, 4COOH) and (6'OH, 3H(+), 4COOH); (3) the unassigned peak near 400
      nm in the experimental absorption spectra at pH 1 is assigned to the absorption
      from the equilibrium ground state to the first excited state of (6'OH, 3H(+),
      4COOH); and (4) the unassigned peak at 610 nm in the experimental fluorescence
      spectra corresponds to the transition from the equilibrium first excited state to
      the ground state of (6'OH, 4COO(-)).

PMID- 22364398
TI  - Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly
      predicts cancer progression.
AB  - Emerging evidence has indicated a role of the bone morphogenetic proteins (BMP)
      in the pathogenesis of certain cancers. The signaling of BMP family members is
      tightly regulated by their antagonists, including noggin and SOST, which are, in
      turn, positively regulated by BMP, thereby forming a negative feedback loop.
      Consequently, the expression of these antagonists should be taken into account in
      studies on the prognostic significance of BMP. In the present paper, we
      correlated protein and mRNA expression levels of BMP6, noggin and SOST, alone or
      in combination, with patient survival in various types of cancer. We found that
      BMP6 alone was not significantly correlated with esophageal squamous cell
      carcinoma patient survival. Instead, a high level of inhibitor of differentiation
      1, a downstream factor of BMP6, was associated with shorter survival in patients
      whose tumors stained strongly for BMP6. Knockdown of noggin in esophageal cancer
      cell line EC109, which expresses BMP6 strongly and SOST weakly, enhanced the non
      adherent growth of the cells. Noggin and SOST expression levels, when analyzed
      alone, were not significantly correlated with patient survival. However, high
      BMP6 activity, defined by strong BMP6 expression coupled with weak noggin or SOST
      expression, was significantly associated with shorter survival in esophageal
      squamous cell carcinoma patients. We further confirmed that BMP6 activity could
      be used as a prognostic indicator in prostate, bladder and colorectal cancers,
      using publicly available data on BMP6, noggin and SOST mRNA expression and
      patient survival. Our results strongly suggest that BMP6, noggin and SOST could
      be used in combination as a prognostic indicator in cancer progression.

PMID- 22364399
TI  - Anatomical repair of double outlet right ventricle associated with complete
      atrioventricular septal defect and pulmonary stenosis: extending the indications
      for aortic translocation.
AB  - The combination of double outlet right ventricle (DORV) and complete
      atrioventricular septal defect (CAVSD) remains a surgical challenge for
      anatomical repair. Inasmuch as the ventricular septal defect is noncommitted in
      this combination, the major concern regarding anatomical repair is the
      reconstruction of the unobstructed left ventricular outflow tract without
      compromising right ventricular volume and the right ventricular outflow tract. We
      report on a patient who underwent an anatomical repair using aortic root
      translocation for DORV with CAVSD and pulmonary stenosis (PS).

PMID- 22364400
TI  - Persistence of stimulants in children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine the persistence of three newly initiated stimulant
      preparations among Medicaid children and adolescents with attention
      deficit/hyperactivity disorder (ADHD) diagnosis. METHODS: A retrospective
      longitudinal claims analysis was conducted by using Medicaid analytical eXtract
      data of four states. The study focused on patients between 6 and 19 years of age
      with ADHD diagnosis and a stimulant prescription from January 2003 to December
      2005. Stimulants were grouped into short-acting stimulants (SAS), intermediate
      acting stimulants (IAS), and long-acting stimulants (LAS). Persistence was
      measured by totaling the number of days the patient remained on the index
      stimulant therapy from the index prescription date provided the refill gap
      between two consecutive stimulant claims was no more than 30 days. All the
      stimulant recipients were uniformly followed for 1 year (365 days). Survival time
      ratios (STR) were calculated by using accelerated failure time models to examine
      variation in index stimulant persistence for each stimulant class. RESULTS: Among
      the 46,135 patients with ADHD continuously followed for 1 year, 8,260 were SAS
      users, 4,314 were IAS users, and 33,561 were LAS users. Children who received IAS
      medications had 4% shorter persistence (STR, 0.96 [95% confidence interval [CI],
      0.93-0.98]) when compared with those who received SAS medications, whereas those
      who received index LAS medications had 29% longer persistence (STR, 1.29 [95% CI,
      1.27-1.32]). Multivariate accelerated failure time models revealed that Blacks
      and Hispanics had consistently lower persistence than their counterparts. Foster
      care was positively associated with index stimulant persistence in the three
      stimulant types. Further, addition of another stimulant and other psychotropic
      medications significantly improved persistence of index stimulant in all three
      stimulant classes. CONCLUSIONS: LAS had comparatively longer persistence than
      other stimulants. An understanding of demographic and clinical characteristics
      that influence treatment continuation can help improve stimulant persistence
      rates in ADHD.

PMID- 22364401
TI  - Low-dose sertraline-induced erythema multiforme in a child.

PMID- 22364402
TI  - Modulation of attention-deficit/hyperactivity disorder symptoms by short- and
      long-acting methylphenidate over the course of a day.
AB  - The purpose of this study was to investigate whether a long-acting
      methylphenidate formulation (MPH-ret) is as effective as two doses of immediate
      release methylphenidate (MPH-IR) in reducing attention-deficit/hyperactivity
      disorder (ADHD) symptoms including inattention, impulsivity, and hyperactivity
      during the course of the day. Two groups of children (n=18 each) with ADHD aged
      between 8 and 12 years completed a continuous performance test in combination
      with a motion-tracking system four times a day within 8 hours. Inattention
      (standard deviation of reaction time), impulsivity (commission error rate), and
      hyperactivity (path length of the headband) were simultaneously measured. We
      included a control group (n=20) to rule out circadian fluctuations of attentional
      performance and motor activity. We observed a postlunch dip in attentional
      performance and an increasing trend of motor activity throughout the day whereas
      impulsivity remained stable in controls. The MPH-ret and MPH-IR groups had
      comparable treatment effects on measures of hyperactivity and inattention and
      normalized participant performance to control levels. In contrast, MPH-IR seems
      to have an advantage over MPH-ret in impulsivity treatments. Thus, our data
      suggest that it is crucial to assess the different domains of ADHD symptoms
      precisely over the course of a day to determine the optimal titration and
      stimulant formulation for a person with ADHD.

PMID- 22364403
TI  - Atypical antipsychotic medications to control symptoms of delirium in children
      and adolescents.
AB  - BACKGROUND: Atypical antipsychotics have been documented to be effective in the
      management of delirium in adults, but despite considerable need, their use has
      been less studied in pediatric patients. OBJECTIVE: A retrospective chart review
      was done to describe the use of atypical antipsychotics in controlling symptoms
      of delirium in children and adolescents. METHODS: Pharmacy records at Children's
      Hospital Los Angeles were reviewed to identify patients to whom antipsychotic
      agents were dispensed over a 24-month period. Psychiatric inpatient consultations
      during the same 24-month period were reviewed. Patients 1-18 years old diagnosed
      with delirium given antipsychotics constituted the study population. Delirium
      Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when
      possible, at time antipsychotic was started to confirm the initial diagnosis of
      delirium and evaluate symptom severity, and again when antipsychotic was stopped,
      to assess symptom response. RESULTS: Olanzapine (n=78), risperidone (n=13), and
      quetiapine (n=19) were used during the 2 years of the study. Mean patient age,
      length of treatment, and response were comparable for the three medications. For
      patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores
      decreased significantly (p<0.001) with antipsychotic without significant adverse
      side effects. CONCLUSION: Although randomized placebo-controlled studies are
      needed, atypical antipsychotic medications appeared to be effective and safe for
      managing delirium symptoms in pediatric patients while underlying etiology was
      addressed.

PMID- 22364404
TI  - Evaluation of the safety, efficacy, and versatility of a new surgical energy
      device (THUNDERBEAT) in comparison with Harmonic ACE, LigaSure V, and EnSeal
      devices in a porcine model.
AB  - BACKGROUND: THUNDERBEATTM (TB) (Olympus, Japan) simultaneously delivers
      ultrasonically generated frictional heat energy and electrically generated
      bipolar energy. The aim of this study was to evaluate the versatility, bursting
      pressure, thermal spread, and dissection time of the TB compared with
      commercially available devices: Harmonic((r)) ACE (HA) (Ethicon Endo-Surgery,
      USA), LigaSureTM V (LIG) (Covidien, USA), and EnSeal((r)) (Ethicon). METHODS: An
      acute study was done with 10 female Yorkshire pigs (weighing 30-35 kg). Samples 2
      cm long of small (2-3 mm)-, medium (4-5 mm)-, and large (6-7 mm)-diameter vessels
      were created. One end of the sample was sent for histological evaluation, and the
      other was used for burst pressure testing in a blinded fashion. Versatility was
      defined as the performance of the surgical instrument based on the following five
      variables, using a score from 1 to 5 (1=worst, 5=best), adjusted by coefficient
      of variable importance with weighted distribution: hemostasis, 0.275; histologic
      sealing, 0.275; cutting, 0.2; dissection, 0.15; and tissue manipulation, 0.1.
      There were 80 trials per vessel group and 60 trials per instrument group, giving
      a total of 240 samples. RESULTS: Versatility score was higher (P<.01) and
      dissection time was shorter (P<.01) using TB compared with the other three
      devices. Bursting pressure was similar among TB and the other three instruments.
      Thermal spread at surgery was similar between TB and HA (P=.4167), TB and EnSeal
      (P=.6817), and TB and LIG (P=.8254). Difference in thermal spread was noted
      between EnSeal and HA (P=.0087) and HA and LIG (P=.0167). CONCLUSION: TB has a
      higher versatility compared with the other instruments tested with faster
      dissection speed, similar bursting pressure, and acceptable thermal spread. This
      new energy device is an appealing, safe alternative for cutting, coagulation, and
      tissue dissection during surgery and should decrease time and increase
      versatility during surgical procedures.

PMID- 22364405
TI  - Community volunteers can improve breastfeeding among children under six months of
      age in the Democratic Republic of Congo crisis.
AB  - BACKGROUND: Malnutrition is a major public health problem in developing countries
      and exclusive breastfeeding is an efficient strategy that can be used to prevent
      malnutrition and reduce child mortality. The objective of this study is to
      evaluate the effectiveness of community volunteers in promoting exclusive
      breastfeeding from birth in an area of endemic malnutrition. METHODS: This
      evaluation analyzed the impact of the community-based nutrition project in Katana
      health district of the Democratic Republic of Congo from 2004 to 2006. Each of
      the villages in this sector had a nutritional village committee made up of five
      members responsible for continuously working to raise awareness of the importance
      of exclusive breastfeeding from birth among pregnant women and community leaders
      in their respective villages. The program worked with community volunteers with a
      mean age of 37 years, most of whom were married (86%). Eighty percent of the
      community volunteers had completed secondary school or a higher level of
      education. Data related to the period of exclusive breastfeeding and to the
      number of visits made to the health services for 208 children. The data were
      compared with data from 178 infants collected from another health sector, which
      had never developed a community-based nutrition program. RESULTS: The duration of
      exclusive breastfeeding from birth (median, range) was 6 months (2 to 7) in the
      intervention area compared with 4 months (1 to 6) in the comparison area (p <
      0.001). The proportion of infants receiving exclusive breastfeeding at six months
      of age was higher in the intervention area than in the comparison area: 57.7%
      (95% Confidence Interval, CI, 50.9 to 64.5) versus 2.7% (95%CI, 1.1 to 6.6) (p <
      0.001). The intervention group had a higher mean weight at 12 months (standard
      deviation): 8.42 kg (1.41) compared to 7.97 kg (1.02), although this difference
      was not statistically significant (p = 0.055). CONCLUSIONS: The promotion of
      breastfeeding by community volunteers in an area of endemic malnutrition in rural
      Democratic Republic of Congo increased the duration of exclusive breastfeeding
      from birth.

PMID- 22364406
TI  - Direct determination of minority carrier diffusion lengths at axial GaAs nanowire
      p-n junctions.
AB  - Axial GaAs nanowire p-n diodes, possibly one of the core elements of future
      nanowire solar cells and light emitters, were grown via the Au-assisted vapor
      liquid-solid mode, contacted by electron beam lithography, and investigated using
      electron beam induced current measurements. The minority carrier diffusion
      lengths and dynamics of both, electrons and holes, were determined directly at
      the vicinity of the p-n junction. The generated photocurrent shows an exponential
      decay on both sides of the junction and the extracted diffusion lengths are about
      1 order of magnitude lower compared to bulk material due to surface
      recombination. Moreover, the observed strong diameter-dependence is well in line
      with the surface-to-volume ratio of semiconductor nanowires. Estimating the
      surface recombination velocities clearly indicates a nonabrupt p-n junction,
      which is in essential agreement with the model of delayed dopant incorporation in
      the Au-assisted vapor-liquid-solid mechanism. Surface passivation using ammonium
      sulfide effectively reduces the surface recombination and thus leads to higher
      minority carrier diffusion lengths.

PMID- 22364407
TI  - Disseminated lichen planus due to a zinc allergy.

PMID- 22364409
TI  - Photoinduced electron transfer in folic acid investigated by ultrafast infrared
      spectroscopy.
AB  - Conformational control of excited-state intramolecular electron transfer (ET) in
      folic acid (FA) has been investigated using femtosecond time-resolved infrared
      (TRIR) spectroscopy. Ultrafast excited-state ET between the pterin and the 4
      aminobenzoyl subunits of FA is observed for the anionic form (at pH 10.0). An ET
      lifetime of 2.5 ps is estimated from Marcus theory for FA in the "U"
      conformation, in close agreement with the observed lifetime of 2.0 ps. Return to
      the ground state through the reverse ET reaction happens almost as rapidly,
      within 5 ps, resulting in rapid quenching of the singlet excited state. In mixed
      water:dimethyl sulfoxide solvent, ET becomes more unfavorable as FA adopts a more
      open conformation, thereby increasing the effective donor-acceptor distance and
      reducing the coupling energy. In contrast, no ET is observed for the cationic
      form of FA at low pH (6.0). In this case, the initial singlet excited state is
      localized on the pterin moiety of FA, and the excited-state charge distribution
      evolves with time. The charge redistribution in the pterin that occurs with
      intersystem crossing to the triplet state is characterized by changes in the
      transient IR spectrum. The excited-state lifetime is much longer in the absence
      of an ET quenching pathway. These results provide new insight into the mechanism
      of photodegradation and toxicity of FA. Ultrafast intramolecular ET in closed
      conformations of FA rapidly quenches the excited state and prevents efficient
      triplet state formation. Thus, conformations of FA that allow ultrafast intra-ET
      and rapid quenching of the singlet excited state play a key role in inhibiting
      pathological pathways following photoexcitation of FA.

PMID- 22364410
TI  - Effects of immunosuppressive therapy on wound healing.
AB  - Immunosuppressive therapy is increasingly being used in clinical practice and has
      been shown to affect wound healing to varying degrees. This article looks at the
      effects of the newer immunosuppressive agents on wound healing. It is shown that
      wound healing is impaired via different mechanisms. Some of the animal and human
      studies are reviewed in more detail. It is shown that some of the newer agents
      affect wound healing to such an extent that reduction or avoidance of these drugs
      until complete wound healing is achieved is advocated. More research is required
      for these newer agents to determine the most appropriate time to introduce them.

PMID- 22364411
TI  - Screening for inborn errors of metabolism in high-risk children: a 3-year pilot
      study in Zhejiang Province, China.
AB  - BACKGROUND: Tandem mass spectrometry (MS/MS) has been available in China for 8
      years. This technique makes it possible to screen for a wide range of previously
      unscreened inborn errors of metabolism (IEM) using a single test. This 3-year
      pilot study investigated the screening, diagnosis, treatment and outcomes of IEM
      in symptomatic infants and children. METHODS: All children encountered in the
      Newborn Screening Center of Zhejiang Province during a 3-year period with
      symptoms suspicious for IEM were screened for metabolic diseases. Dried blood
      spots were collected and analyzed by tandem mass spectrometry. The diagnoses were
      further confirmed by clinical symptoms and biochemical analysis. Neonatal
      intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase
      deficiency and primary carnitine deficiency were confirmed by DNA analysis.
      RESULTS: A total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a
      median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these,
      62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were
      males and 27 females and the median age was 3.55 months (range 0.07-143.9
      months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had
      organic acidemias and nine (14.5%) had fatty acid oxidation disorders.
      CONCLUSIONS: Because most symptomatic patients are diagnosed at an older age,
      mental retardation and motor delay are difficult to reverse. Additionally, poor
      medication compliance reduces the efficacy of treatment. More extensive newborn
      screening is thus imperative for ensuring early diagnosis and enhancing the
      treatment efficacy of IEM.

PMID- 22364412
TI  - Tail morphology controls DNA release in two Salmonella phages with one
      lipopolysaccharide receptor recognition system.
AB  - Bacteriophages use specific tail proteins to recognize host cells. It is still
      not understood to molecular detail how the signal is transmitted over the tail to
      initiate infection. We have analysed in vitro DNA ejection in long-tailed
      siphovirus 9NA and short-tailed podovirus P22 upon incubation with Salmonella
      typhimurium lipopolysaccharide (LPS). We showed for the first time that LPS alone
      was sufficient to elicit DNA release from a siphovirus in vitro. Crystal
      structure analysis revealed that both phages use similar tailspike proteins for
      LPS recognition. Tailspike proteins hydrolyse LPS O antigen to position the phage
      on the cell surface. Thus we were able to compare in vitro DNA ejection processes
      from two phages with different morphologies with the same receptor under
      identical experimental conditions. Siphovirus 9NA ejected its DNA about 30 times
      faster than podovirus P22. DNA ejection is under control of the conformational
      opening of the particle and has a similar activation barrier in 9NA and P22. Our
      data suggest that tail morphology influences the efficiencies of particle opening
      given an identical initial receptor interaction event.

PMID- 22364413
TI  - Visuomotor and audiomotor processing in continuous force production of oral and
      manual effectors.
AB  - The authors examined force control in oral and manual effectors as a function of
      sensory feedback (i.e., visual and auditory). Participants produced constant
      isometric force via index finger flexion and lower lip elevation to 2 force
      levels (10% and 20% maximal voluntary contraction) and received either online
      visual or online auditory feedback. Mean, standard deviation, and coefficient of
      variation of force output were used to quantify the magnitude of force
      variability. Power spectral measures and approximate entropy of force output were
      calculated to quantify the structure of force variability. Overall, it was found
      that the oral effector conditions were more variable (e.g., coefficient of
      variation) than the manual effector conditions regardless of sensory feedback. No
      effector differences were found for the structure of force variability with
      visual or auditory feedback. Oral and manual force control appears to involve
      different control mechanisms regulating continuous force production in the
      presence of visual or auditory feedback.

PMID- 22364415
TI  - Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in
      a renal transplant recipient.
AB  - Abstract   Calcific uremic arteriolopathy (CUA) is a rare but life-threatening
      disorder of arteriolar calcification. It frequently leads to severe ischemia,
      intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually
      occurs in patients with chronic kidney disease (CKD), especially those on
      dialysis, and its occurrence is rare in kidney transplant recipients. The
      treatment of this disorder is not clearly defined, and no randomized prospective
      trials are available. Treatment has focused on optimizing dialysis treatment,
      control of bone mineral parameters, wound care, experimental anticalcification
      therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric
      oxygen. Such treatments are based on the pathophysiological considerations and
      evidences from case reports or series. Recently, several cases have reported
      about the emerging benefits of intravenous sodium thiosulfate (STS) in the
      treatment of CUA. STS has resulted in rapid pain relief, wound healing, and
      prevention of death. We report a case of CUA in a 63-year-old Caucasian man with
      a functioning renal allograft. In this patient, intravenous STS was administered
      for 8 months, which was the principal therapy, which resulted in complete
      resolution of the CUA and skin healing.

PMID- 22364416
TI  - Identification, design and biological evaluation of bisaryl quinolones targeting
      Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).
AB  - A program was undertaken to identify hit compounds against NADH:ubiquinone
      oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport
      chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known
      inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with
      a range of chemoinformatics methods in the rational selection of 17 000 compounds
      for high-throughput screening. Twelve distinct chemotypes were identified and
      briefly examined leading to the selection of the quinolone core as the key target
      for structure-activity relationship (SAR) development. Extensive structural
      exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for
      further biological evaluation. The lead compound within this series 7-chloro-3
      methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl)quinolin-4(1H)-one (CK-2-68) has
      antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is
      selective for PfNDH2 over other respiratory enzymes (inhibitory IC(50) against
      PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability
      in the presence of human liver microsomes. This lead compound and its phosphate
      pro-drug have potent in vivo antimalarial activity after oral administration,
      consistent with the target product profile of a drug for the treatment of
      uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the
      capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc(1), and studies
      to determine the potential advantage of this dual-targeting effect are in
      progress.

PMID- 22364418
TI  - Continuous low-dose-rate radiation of radionuclide phosphorus-32 for hemangiomas.
AB  - The study goal was to clarify the therapeutic effect and the absorbed dose of
      radionuclide phosphorus-32 for skin hemangiomas and the consequent risk of side
      effects in these patients. Phosphorus-32 is an beta emitter and is used for skin
      hemangioma treatment. In comparison with the few Gy per minute of the linear
      accelerators, the dose rate of phosphorus-32 for hemangiomas is much <1 Gy/hour;
      so, the latter is called low-dose-rate radiation. To achieve the therapeutic
      dose, continuous hours or days of radiation is necessary. For strawberry
      hemangiomas, the phosphorus-32 applicator was tightly placed on the lesion site
      for several hours until reaching therapeutic dose. The absorbed dose was
      estimated by radiochromic films. The absorbed dose of phosphorus-32 irradiation
      declined exponentially with a depth from 0 to 2.5 mm. Of the 316 patients with
      strawberry hemangiomas, the lesion disappeared completely within 3 months after
      one-time treatment in 259 cases (82%). For cavernous hemangiomas, 370KBq
      phosphorus-32 colloid was injected into the hemangioma each square centimeter,
      and the absorbed radiation was estimated by theoretical calculation. Forty-two of
      the 58 patients with cavernous hemangiomas (72%) had lesions that completely
      disappeared within 3 months after receiving one to six treatments. Thus, the
      phosphorus-32 for strawberry hemangiomas and the chromium phosphate-32 colloid
      for cavernous hemangiomas were clearly efficacious.

PMID- 22364417
TI  - Identification, design and biological evaluation of heterocyclic quinolones
      targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).
AB  - Following a program undertaken to identify hit compounds against NADH:ubiquinone
      oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite
      Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68,
      a molecule suitable for further development. In order to reduce ClogP and improve
      solubility of CK-2-68 incorporation of a variety of heterocycles, within the side
      chain of the quinolone core, was carried out, and this approach led to a lead
      compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the
      enzyme and whole cell P. falciparum (IC(50) = 15 nM PfNDH2; IC(50) = 54 nM (3D7
      strain of P. falciparum) with notable oral activity of ED(50)/ED(90) of 1.87/4.72
      mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when
      formulated as a phosphate salt. Analogues in this series also demonstrate
      nanomolar activity against the bc(1) complex of P. falciparum providing the
      potential added benefit of a dual mechanism of action. The potent oral activity
      of 2-pyridyl quinolones underlines the potential of this template for further
      lead optimization studies.

PMID- 22364420
TI  - Universal features of the melt elasticity of interacting polymer nanocomposites.
AB  - We study the structure and linear viscoelasticity of interacting polymer
      nanocomposites based on mixtures of poly(ethylene oxide) and fumed silica
      particles. The filler is dispersed within the polymer using two different
      techniques which lead to different dispersion states. The analysis of the dynamic
      response of our systems highlights the formation of a stress-bearing network
      above a critical volume fraction, Phi(c). Extending a two-phase model used to
      describe weakly interacting systems, we show that above Phi(c) the melt-state
      elasticity of the composites arises from the independent contributions of a
      polymer-particle network and a viscous matrix. We also find that, although Phi(c)
      depends on the initial state of dispersion, the network elasticity scales with
      volume fraction following a universal power-law, with an exponent nu ~ 1.8. Such
      a scaling law has been recently predicted for the stress-bearing mechanism
      governed by polymer-mediated interactions.

PMID- 22364419
TI  - Long-term outcome following imatinib therapy for chronic myelogenous leukemia,
      with assessment of dosage and blood levels: the JALSG CML202 study.
AB  - A prospective multicenter Phase II study was performed to examine the efficacy
      and safety of imatinib therapy in newly diagnosed Japanese patients with chronic
      phase CML. Patients were scheduled to receive imatinib 400 mg daily. Plasma
      imatinib concentrations were measured by liquid chromatography-tandem mass
      spectrometry. In 481 evaluable patients, estimated 7-year overall survival (OS)
      and event-free survival (EFS) at a median follow-up of 65 months were 93% and
      87%, respectively. Because imatinib dosage was reduced in many patients due
      mainly to adverse events, subgroup analysis was performed according to the mean
      daily dose during the first 24 months of treatment: >=360 mg (400-mg group; n =
      294), 270-359 mg (300-mg group; n = 90) and <270 mg (200-mg group; n = 67). There
      were no significant differences in OS and EFS between the 300- and 400-mg groups;
      however, cumulative rates of complete cytogenetic and major molecular responses
      differed significantly between the two groups. There were no significant
      differences in mean imatinib trough levels between these two groups for the
      patients in whom trough levels had been measured. Survival and efficacy in the
      200-mg group were markedly inferior to the former two groups. These results
      suggest that, although a daily dose of 400 mg imatinib is associated with better
      outcomes, 300 mg imatinib may be adequate for a considerable number of Japanese
      patients who are intolerant to 400 mg imatinib. Blood level monitoring would be
      useful to determine the optimal dose of imatinib.

PMID- 22364421
TI  - Transcranial Doppler quantification of residual shunt after percutaneous patent
      foramen ovale closure: correlation of device efficacy with intracardiac anatomic
      measures.
AB  - BACKGROUND: Percutaneous, mechanical closure of defects of the atrial septum
      fails to completely resolve shunting in up to 20% of cases. Little is known about
      the factors associated with device failure. METHODS: We measured the left atrial
      opening (X), right atrial opening (Z), tunnel length (Y), septum secundum, device
      septum primum separation, and tunnel compressibility of the patent foramen ovale
      (PFO) in 301 patients with cryptogenic neurological events, PFO anatomy, and
      severe Valsalva shunting (Spencer Grade 5-5+). All patients then underwent
      percutaneous closure with the GORE(r)HELEX Septal Occluder device and were
      evaluated at 3 months for residual shunt by transcranial Doppler (TCD). RESULTS:
      Severe residual Valsalva shunt (TCD Grade 5-5+) was found at 3 months in 21 of
      301 (7%) patients. X, Y, and Z were associated with failure with a high degree of
      statistical significance, whereas the width of the septum secundum, device-septum
      primum separation, and tunnel compressibility were not. An unanticipated finding
      was that 14 of 35 (40%) patients sized with a large balloon failed compared with
      9 of 280 (3%) sized with a small balloon (P < 0.0001). In the multivariate
      logistic regression model, X (P = < 0.0001) and balloon size (P < 0.0001) were
      both strong predictors of failure. CONCLUSIONS: In an intracardiac
      echocardiography-defined PFO population, characterized by severe baseline
      Valsalva shunt and a high incidence of persistent (rest) shunting, association of
      six intracardiac measurements to closure device failure by multivariate logistic
      regression showed that the width of the left atrial opening was a strong
      predictor of residual shunting. An unanticipated finding was that use of a large
      sizing balloon was also strongly associated with failure.

PMID- 22364422
TI  - Intramolecular oxidative diamination and aminohydroxylation of olefins under
      metal-free conditions.
AB  - A metal-free procedure that is simple to operate and convenient to handle was
      developed for the facile intramolecular oxidative diamination of olefins using an
      iodobenzene diacetate oxidant and a halide additive to furnish bisindolines at
      room temperature. The present reaction is featured by mild conditions, a broad
      substrate scope, and excellent functional group tolerance. The same protocol was
      successfully extended to the aminohydroxylation.

PMID- 22364423
TI  - New thoughts on talk therapies.

PMID- 22364424
TI  - Doing the best I can do: moral distress in adolescent mental health nursing.
AB  - The purpose of this research was to explore the process used by mental health
      nurses working with adolescents to ameliorate the experience of moral distress.
      Using grounded theory methodology, a substantive theory was developed to explain
      the process. All the incidents that led to the experience of moral distress were
      related to safety and resulted in the nurses asking themselves the question, "Is
      this the best I can do?" Engaging in dialogue was the primary means nurses used
      to work through the experience of moral distress. Engaging in dialogue was an
      ongoing process, and nurses sought out dialogue with a variety of people as they
      tried to make sense of their experience. Participants identified qualities of
      dialogue that were helpful or unhelpful as they sought to resolve their moral
      distress. Participants who had a positive experience of dialogue were able to
      answer the "Is this the best I can do" question satisfactorily and continue
      working with adolescents with a renewed focus on the therapeutic relationship.
      Participants who had a negative experience of dialogue are unable to answer the
      question and either left the unit or agency or talked about leaving.

PMID- 22364425
TI  - The characteristics of consumers receiving case management in the community: a
      review of literature.
AB  - Mental health nurses increasingly provide care for consumers in the community who
      once would have received treatment in psychiatric inpatient units. The purpose of
      this review is to determine the characteristics of these consumers. We searched
      electronic databases and obtained information on some of the characteristics of
      community mental health consumers. For some nurses, over half of their caseloads
      are consumers with schizophrenia. Up to about one-third of consumers may be
      involuntary, but this proportion varies considerably. Impairments of health and
      social functioning appear common among consumers of community mental health
      services. This study identifies the need for greater interrogation of national
      databases to enhance understanding of community caseloads.

PMID- 22364426
TI  - The relationship among young adult college students' depression, anxiety, stress,
      demographics, life satisfaction, and coping styles.
AB  - Recent research indicates that young adult college students experience increased
      levels of depression, anxiety, and stress. It is less clear what strategies
      college health care providers might use to assist students in decreasing these
      mental health concerns. In this paper, we examine the relative importance of
      coping style, life satisfaction, and selected demographics in predicting
      undergraduates' depression, anxiety, and stress. A total of 508 full-time
      undergraduate students aged 18-24 years completed the study measures and a short
      demographics information questionnaire. Coping strategies and life satisfaction
      were assessed using the Brief COPE Inventory and an adapted version of the Brief
      Students' Multidimensional Life Satisfaction Scale. Depression, anxiety, and
      stress were measured using the Depression Anxiety and Stress Scale-21 (DASS-21).
      Multiple regression analyses were used to examine the relative influence of each
      of the independent variables on depression, anxiety, and stress. Maladaptive
      coping was the main predictor of depression, anxiety, and stress. Adaptive coping
      was not a significant predictor of any of the three outcome variables. Reducing
      maladaptive coping behaviors may have the most positive impact on reducing
      depression, anxiety, and stress in this population.

PMID- 22364427
TI  - A lonely life journey bordered with struggle: being a sibling of an individual
      with psychosis.
AB  - Research suggests that siblings of individuals with severe mental illness are
      affected by the situation and that health care services seem to be inadequate in
      meeting their needs for support. The aim of this study is to explore how siblings
      of individuals with a psychotic illness, and who have participated in a support
      group, experience their situation. Thirteen individuals participated in focus
      group interviews, which were analyzed by inductive content analysis. The findings
      were interpreted into an overall single theme: A lonely life journey bordered
      with struggle. This theme consists of three categories: facing existential
      thoughts, facing ambiguity in approach and engagement, and facing disparate
      attitudes and expectations.

PMID- 22364428
TI  - The ethos of physical activity delivery in mental health: a narrative study of
      service user experiences.
AB  - Our research into the physical activity experiences of people with severe mental
      illness has led us to take seriously the social and cultural environment in which
      physical activity is delivered. In this study, through narrative methodology, we
      examine service user accounts of physical activity to illuminate the
      characteristics of physical activity groups that are experienced as positive,
      helpful, or beneficial. We present several qualities and show how effective
      leadership and coaching is central to these qualities being present. We conclude
      that it is not so much what activity is delivered, but how it is delivered that
      is critical for sustained participation and positive outcomes.

PMID- 22364429
TI  - Exploring barriers to primary care for patients with severe mental illness:
      frontline patient and provider accounts.
AB  - The goal of this study was to obtain in-depth descriptions of barriers to primary
      care for adults with serious mental illness (SMI) and to provide solutions to
      these barriers. Qualitative interviews were administered to mental health and
      medical providers, as well as patients. Several major themes were reported
      including: poor access to care; patient limitations (e.g., psychopathology,
      cognitive difficulties); societal, health care system, and provider bias;
      integrated/fragmented care, communication difficulties; and quality of care
      issues. Results point to a need for nursing professionals to continue to improve
      access to medical care for this population, as well as to continue to integrate
      mental health and primary care.

PMID- 22364430
TI  - Mental illness training for licensed staff in long-term care.
AB  - Licensed care staff working in long-term care facilities may be poorly prepared
      to work with residents with mental illness. This research reports on the program
      evaluation of Caring Skills: Working with Mental Illness, a training program
      delivered on the Internet. It was tested with a randomized treatment-control
      design, with an eight-week follow-up. The training provided video-based
      behavioral skills and knowledge training. Measures included video situations
      testing and assessment of psycho-social constructs including empathy and
      stigmatization. ANCOVA analysis at 4-weeks posttest showed significant positive
      effects with medium-large effect sizes, which were largely maintained at the 8
      week follow-up. The training was well-received by the users.

PMID- 22364432
TI  - Mental health care and health literacy.

PMID- 22364433
TI  - Chronic calcaneal osteomyelitis associated with soft-tissue defect could be
      successfully treated with platelet-rich plasma: a case report.
AB  - Chronic osteomyelitis associated with soft-tissue defect following surgical
      management is a severe complication for orthopaedic surgeons. Traditionally, the
      treatment protocol for the notorious complication involved thorough debridement,
      bone grafting, long-term antibiotic use and flap surgery. Alternatively, platelet
      rich plasma (PRP), a high concentration of platelets collected via
      centrifugation, has been successfully used as an adjuvant treatment for bone and
      soft-tissue infection in medical practices. PRP has numerous significant
      advantages, including stypsis, inflammation remission and reducing the amount of
      infected fluid. It increases bone and soft-tissue healing and allows fewer
      opportunities for transplant rejection. Through many years of studies showing the
      advantages of PRP, it has become preferred organic product for the clinical
      treatment of infections, especially for chronic osteomyelitis associated with
      soft-tissue defect. To promote the clinical use of this simple and efficacious
      technique in trauma, we report the case of a patient with chronic calcaneal
      osteomyelitis associated with soft-tissue defect that healed uneventfully with
      PRP.

PMID- 22364434
TI  - The interplay between input and initial biases: asymmetries in vowel perception
      during the first year of life.
AB  - Vowels with extreme articulatory-acoustic properties act as natural referents.
      Infant perceptual asymmetries point to an underlying bias favoring these referent
      vowels. However, as language experience is gathered, distributional frequency of
      speech sounds could modify this initial bias. The perception of the /i/-/e/
      contrast was explored in 144 Catalan- and Spanish-learning infants (2 languages
      with a different distribution of vowel frequency of occurrence) at 4, 6, and 12
      months. The results confirmed an acoustic bias at 4 and 6 months in all infants.
      However, at 12 months, discrimination was not affected by the acoustic bias but
      by the frequency of occurrence of the vowel.

PMID- 22364435
TI  - The French OQALI survey on dairy products: comparison of nutrient contents and
      other nutrition information on labels among types of brands.
AB  - BACKGROUND: Depending on their spending power, consumers may choose foodstuffs
      from more or less expensive types of brands (national, retailer, economy-line
      retailer or discount brands). The present study, on dairy products, assesses the
      nutritional composition and the frequencies of labelled nutrition parameters,
      according to types of brands. METHODS: The 1646 most consumed dairy products were
      collected. Nutrient contents and other labelled nutrition parameters provided on
      the packaging (i.e. nutrition and health claims, nutrition guidelines such as
      guideline daily amounts, consumption advice and information on added vitamins and
      minerals) were captured in the French branded product composition database
      (OQALI). RESULTS: Significant differences between brands were found for energy,
      protein, fat, saturates, carbohydrate, sugars, dietary fibre, calcium and sodium,
      in four of six dairy groups studied, but not systematically. National brands and
      retailer brands provided more detailed nutrition labelling and more frequent
      nutrition claims than cheaper brands. More retailer brand products provided
      nutrition guidelines and consumption advice than the other branded products.
      National brand products more frequently contained added vitamins and minerals and
      more frequently bore health claims. CONCLUSIONS: Nutrient contents of the cheaper
      brands of dairy products did not vary systematically from more expensive ones.
      However, national brands and retailer brands products provided more nutrition
      information on labels than the cheaper ones. There should be more detailed
      studies comparing different types of brands regarding labelling practices for
      nutrient contents and other nutrition information about foodstuffs to help
      prepare public health recommendations, adapted to all consumers, regardless of
      their income.

PMID- 22364436
TI  - Polarization-induced local pore-wall functionalization for biosensing: from
      micropore to nanopore.
AB  - The use of biological-probe-modified solid-state pores in biosensing is currently
      hindered by difficulties in pore-wall functionalization. The surface to be
      functionalized is small and difficult to target and is usually chemically similar
      to the bulk membrane. Herein, we demonstrate the contactless
      electrofunctionalization (CLEF) approach and its mechanism. This technique
      enables the one-step local functionalization of the single pore wall fabricated
      in a silica-covered silicon membrane. CLEF is induced by polarization of the pore
      membrane in an electric field and requires a sandwich-like composition and a
      conducting or semiconducting core for the pore membrane. The defects in the
      silica layer of the micropore wall enable the creation of an electric pathway
      through the silica layer, which allows electrochemical reactions to take place
      locally on the pore wall. The pore diameter is not a limiting factor for local
      wall modification using CLEF. Nanopores with a diameter of 200 nm fabricated in a
      silicon membrane and covered with native silica layer have been successfully
      functionalized with this method, and localized pore-wall modification was
      obtained. Furthermore, through proof-of-concept experiments using ODN-modified
      nanopores, we show that functionalized nanopores are suitable for translocation
      based biosensing.

PMID- 22364437
TI  - Impact of metabolic comorbidity on the association between body mass index and
      health-related quality of life: a Scotland-wide cross-sectional study of 5,608
      participants.
AB  - BACKGROUND: The prevalence of obesity is rising in Scotland and globally.
      Overall, obesity is associated with increased morbidity, mortality and reduced
      health-related quality of life. Studies suggest that "healthy obesity" (obesity
      without metabolic comorbidity) may not be associated with morbidity or mortality.
      Its impact on health-related quality of life is unknown. METHODS: We extracted
      data from the Scottish Health Survey on self-reported health-related quality of
      life, body mass index (BMI), demographic information and comorbidity. SF-12
      responses were converted into an overall health utility score. Linear regression
      analyses were used to explore the association between BMI and health utility,
      stratified by the presence or absence of metabolic comorbidity (diabetes,
      hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for
      potential confounders (age, sex and deprivation quintile). RESULTS: Of the 5,608
      individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had
      metabolic comorbidity. There was an inverted U-shaped relationship whereby health
      utility was highest among overweight individuals and fell with increasing BMI.
      There was a significant interaction with metabolic comorbidity (p = 0.007).
      Individuals with metabolic comorbidty had lower utility scores and a steeper
      decline in utility with increasing BMI (morbidly obese, adjusted coefficient: 
      0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042,
      95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). CONCLUSIONS: The
      adverse impact of obesity on health-related quality of life is greater among
      individuals with metabolic comorbidity. However, increased BMI is associated with
      reduced health-related quality of life even in the absence of metabolic
      comorbidity, casting doubt on the notion of "healthy obesity".

PMID- 22364438
TI  - Functional expression and characterization of five wax ester synthases in
      Saccharomyces cerevisiae and their utility for biodiesel production.
AB  - BACKGROUND: Wax ester synthases (WSs) can synthesize wax esters from alcohols and
      fatty acyl coenzyme A thioesters. The knowledge of the preferred substrates for
      each WS allows the use of yeast cells for the production of wax esters that are
      high-value materials and can be used in a variety of industrial applications. The
      products of WSs include fatty acid ethyl esters, which can be directly used as
      biodiesel. RESULTS: Here, heterologous WSs derived from five different organisms
      were successfully expressed and evaluated for their substrate preference in
      Saccharomyces cerevisiae. We investigated the potential of the different WSs for
      biodiesel (that is, fatty acid ethyl esters) production in S. cerevisiae. All
      investigated WSs, from Acinetobacter baylyi ADP1, Marinobacter
      hydrocarbonoclasticus DSM 8798, Rhodococcus opacus PD630, Mus musculus C57BL/6
      and Psychrobacter arcticus 273-4, have different substrate specificities, but
      they can all lead to the formation of biodiesel. The best biodiesel producing
      strain was found to be the one expressing WS from M. hydrocarbonoclasticus DSM
      8798 that resulted in a biodiesel titer of 6.3 mg/L. To further enhance biodiesel
      production, acetyl coenzyme A carboxylase was up-regulated, which resulted in a
      30% increase in biodiesel production. CONCLUSIONS: Five WSs from different
      species were functionally expressed and their substrate preference characterized
      in S. cerevisiae, thus constructing cell factories for the production of specific
      kinds of wax ester. WS from M. hydrocarbonoclasticus showed the highest
      preference for ethanol compared to the other WSs, and could permit the engineered
      S. cerevisiae to produce biodiesel.

PMID- 22364439
TI  - Bayesian effect estimation accounting for adjustment uncertainty.
AB  - Model-based estimation of the effect of an exposure on an outcome is generally
      sensitive to the choice of which confounding factors are included in the model.
      We propose a new approach, which we call Bayesian adjustment for confounding
      (BAC), to estimate the effect of an exposure of interest on the outcome, while
      accounting for the uncertainty in the choice of confounders. Our approach is
      based on specifying two models: (1) the outcome as a function of the exposure and
      the potential confounders (the outcome model); and (2) the exposure as a function
      of the potential confounders (the exposure model). We consider Bayesian variable
      selection on both models and link the two by introducing a dependence parameter,
      omega, denoting the prior odds of including a predictor in the outcome model,
      given that the same predictor is in the exposure model. In the absence of
      dependence (omega= 1), BAC reduces to traditional Bayesian model averaging (BMA).
      In simulation studies, we show that BAC, with omega > 1, estimates the exposure
      effect with smaller bias than traditional BMA, and improved coverage. We, then,
      compare BAC, a recent approach of Crainiceanu, Dominici, and Parmigiani (2008,
      Biometrika 95, 635-651), and traditional BMA in a time series data set of
      hospital admissions, air pollution levels, and weather variables in Nassau, NY
      for the period 1999-2005. Using each approach, we estimate the short-term effects
      of on emergency admissions for cardiovascular diseases, accounting for
      confounding. This application illustrates the potentially significant pitfalls of
      misusing variable selection methods in the context of adjustment uncertainty.

PMID- 22364440
TI  - Assigning structures to gas-phase peptide cations and cation-radicals. An
      infrared multiphoton dissociation, ion mobility, electron transfer, and
      computational study of a histidine peptide ion.
AB  - Infrared multiphoton dissociation (IRMPD) spectroscopy, using a free-electron
      laser, and ion mobility measurements, using both drift-cell and traveling-wave
      instruments, were used to investigate the structure of gas-phase peptide (AAHAL +
      2H)(2+) ions produced by electrospray ionization. The experimental data from the
      IRMPD spectra and collisional cross section (Omega) measurements were consistent
      with the respective infrared spectra and Omega calculated for the lowest-energy
      peptide ion conformer obtained by extensive molecular dynamics searches and
      combined density functional theory and ab initio geometry optimizations and
      energy calculations. Traveling-wave ion mobility measurements were employed to
      obtain the Omega of charge-reduced peptide cation-radicals, (AAHAL + 2H)(+?), and
      the c(3), c(4), z(3), and z(4) fragments from electron-transfer dissociation
      (ETD) of (AAHAL + 2H)(2+). The experimental Omega for the ETD charge-reduced and
      fragment ions were consistent with the values calculated for fully optimized ion
      structures and indicated that the ions retained specific hydrogen bonding motifs
      from the precursor ion. In particular, the Omega for the doubly protonated ions
      and charge-reduced cation-radicals were nearly identical, indicating negligible
      unfolding and small secondary structure changes upon electron transfer. The
      experimental Omega for the (AAHAL + 2H)(+?) cation-radicals were compatible with
      both zwitterionic and histidine radical structures formed by electron attachment
      to different sites in the precursor ion, but did not allow their distinction. The
      best agreement with the experimental Omega was found for ion structures fully
      optimized with M06-2X/6-31+G(d,p) and using both projection approximation and
      trajectory methods to calculate the theoretical Omega values.

PMID- 22364441
TI  - Reproducibility and variability of the cost functions reconstructed from
      experimental recordings in multifinger prehension.
AB  - The study examines whether the cost functions reconstructed from experimental
      recordings are reproducible over time. Participants repeated the trials on three
      days. By following Analytical Inverse Optimization procedures, the cost functions
      of finger forces were reconstructed for each day. The cost functions were found
      to be reproducible over time: application of a cost function C(i) to the data of
      Day j (i?j) resulted in smaller deviations from the experimental observations
      than using other commonly used cost functions. Other findings are: (a) the 2nd
      order coefficients of the cost function showed negative linear relations with
      finger force magnitudes; (b) the finger forces were distributed on a 2
      dimensional plane in the 4-dimensional finger force space for all subjects and
      all testing sessions; (c) the data agreed well with the principle of
      superposition, i.e. the action of object prehension can be decoupled into the
      control of rotational equilibrium and slipping prevention.

PMID- 22364443
TI  - Pretreatment with pentoxifylline and N-acetylcysteine in liver ischemia
      reperfusion-induced renal injury.
AB  - BACKGROUND AND AIMS: Acute hepatic injury causes systematic inflammatory
      responses which may finally lead to functional disturbances in remote organs. In
      this study, the effects of an inhibitor of inflammatory cytokines
      (pentoxifylline, PTX) and a well-known antioxidant, N-acetylcysteine (NAC), were
      evaluated on renal damage and oxidative stress following liver ischemia
      reperfusion (IR). METHOD: Five groups of six male rats were used. Group 1 was
      sham operated. In group 2, 90 min liver partial ischemia was induced by a clamp
      around both hepatic artery and portal vein and then followed by 4 h of
      reperfusion. In groups 3 and 4, PTX or NAC was injected intraperitoneally before
      the ischemia, while in group 5 both drugs were co-administered. The levels of
      alanine amino-transferase (ALT), aspartate amino-transferase (AST), blood urea
      nitrogen (BUN), and creatinine in serum as well as malonyldialdehyde (MDA) and
      glutathione (GSH) levels and morphological changes in renal tissues were
      assessed. RESULTS: Significant increase in the serum levels of ALT and AST in IR
      group is indicative of liver functional damages. Elevated BUN and renal tissue
      MDA, decreased GSH levels, and morphological damages in IR group demonstrate a
      significant kidney injury and oxidative stress comparing to sham group.
      Administration of PTX alone and PTX + NAC prevented the IR-induced increase in
      renal MDA levels. Administration of both drugs and their co-administration
      prevented the reduction in renal GSH levels and morphological changes.
      CONCLUSION: Pretreatment with PTX and NAC before liver IR may be useful to
      ameliorate renal oxidative damage by preservation of cellular GSH concentration
      and a reduction in MDA levels.

PMID- 22364445
TI  - Technetium-99m labeled pyridyl benzofuran derivatives as single photon emission
      computed tomography imaging probes for beta-amyloid plaques in Alzheimer's
      brains.
AB  - Three novel (99m)Tc-labeled pyridyl benzofuran derivatives were tested as
      potential probes for imaging beta-amyloid plaques using single photon emission
      computed tomography (SPECT). The (99m)Tc and corresponding rhenium complexes were
      synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re
      complexes showed affinity for Abeta(1-42) aggregates (K(i) = 13.6-149.6 nM).
      Biodistribution experiments in normal mice revealed that the (99m)Tc-labeled
      derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min
      postinjection). Notably, [(99m)Tc]BAT-Bp-2 showed a good initial uptake (1.80%
      ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex
      vivo autoradiography with [(99m)Tc]BAT-Bp-2 revealed substantial labeling of beta
      amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not
      in the age-matched controls. [(99m)Tc]BAT-Bp-2 may be a potential SPECT probe for
      imaging beta-amyloid plaques in Alzheimer's brains.

PMID- 22364447
TI  - Advances in primary immunodeficiency diseases in Latin America: epidemiology,
      research, and perspectives.
AB  - Primary immunodeficiencies (PIDs) are genetic disorders of the immune system
      comprising many different phenotypes. Although previously considered rare, recent
      advances in their clinical, epidemiological, and molecular definitions are
      revealing how much we still need to learn about them. For example, geographical
      and ethnic variations as well as the impact of certain practices influence their
      frequency and presentation, making it necessary to consider their study in terms
      of regions. The Latin American Society for Immunodeficiencies was established as
      an organization dedicated to provide scientific support for basic and clinical
      research and to develop tools and educational resources to promote awareness in
      the medical community. Initiatives such as these are positively influencing the
      way PIDs are tackled in these countries, as shown by recent reports and
      publications. This paper provides a historical compilation and a current view of
      the many issues faced by scientists studying these diseases in these countries,
      highlighting the diverse scientific contributions and offering a promising
      perspective for the further developments in this field in Latin America.

PMID- 22364446
TI  - SMRT compounds correct nonsense mutations in primary immunodeficiency and other
      genetic models.
AB  - Within less than 10 years after the realization of the double helix of DNA, the
      ability of aminoglycosides to influence the misreading or readthrough of
      premature termination codons was discovered. It took another three decades to
      clone and sequence disease genes and appreciate the similarity of mutation
      spectra for most inborn errors. Nonsense mutations once again have become the
      target of readthrough compounds. In this brief review, we trace the development
      in our laboratory of the next generation of readthrough agents, small molecule
      readthrough (SMRT) drug-like chemicals, and assays for comparing their in vitro
      activity. Possible mechanisms of action and potential clinical applications are
      considered.

PMID- 22364448
TI  - Towards a systems approach to assessment.

PMID- 22364449
TI  - Medical education in Taiwan.
AB  - Taiwan's medical education system bears a close relationship with its colonial
      and post-colonial history. Since the late nineteenth century, Western medicine,
      Chinese medicine, and the practice of the other forms of traditional healing have
      encountered complex transactions with the state and one another, eventually
      evolving into the present medical system. Nowadays, the mainstream form of
      medical education in Taiwan is a 7-year Western program; other forms of medical
      education include a 5-year graduate program and traditional medicine programs.
      Challenged by the National Health Insurance that emphasizes cost management since
      1995 and criticized by the US National Committee on Foreign Medical Education and
      Accreditation in 1998, medical education reform was implemented by the Taiwan
      Medical Accreditation Council established in 2000. The reform tries to bring
      humanities into various aspects of medical education, including student
      recruitment, curriculum, licensing, and continuing education. Similar to other
      modernization projects, the reform transplants the American and British standards
      to Taiwan. These changes hope to insure the reflective capabilities in physicians
      on the welfare of patients. However, frustration of current and future physicians
      may be deepened if the reform is insensitive to local issues or incapable of
      addressing new global tendencies.

PMID- 22364450
TI  - Twelve tips for developing and implementing an effective surgical simulation
      programme.
AB  - Recent changes to the working practices of physicians in both Europe and the
      United States have led to concerns regarding a reduced exposure of surgical
      trainees to operations and thus a potential for a decreased operative experience
      throughout training. Simulation has been used in many professional fields such as
      the aeronautical industry to prepare pilots prior to real-life situations and has
      become recognised as a potentially useful educational tool in surgery. Surgical
      skills from basic knot-tying to more sophisticated simulation programmes for
      aortic aneurysm surgery have been introduced in surgical training programmes.
      Surgical simulation has been demonstrated to have validity in preparing surgeons
      for operative situations; however, a commitment from educators, protected time
      and well-orchestrated sessions are key elements in the success of a simulation
      programme. This article provides 12 tips for the development and implementation
      of an effective surgical simulation programme informed by experience of large
      scale simulation at an academic institution and relevant literature regarding
      simulation training.

PMID- 22364451
TI  - Twelve tips for effective lecturing in a PBL curriculum.
AB  - BACKGROUND: Retaining lectures in problem-based learning (PBL) curriculum places
      new demands on lecturers. In addition to subject knowledge, the lecturers must
      know the overall aims of the lectures, their context in the course, their
      relation to the subsequent examinations and the underlying educational
      philosophy. AIM: Aim of this communication is to propose ways that will transform
      the traditional didactic lectures into PBL-compliant teaching/learning sessions.
      METHODS: Insights from the self-experience and that of colleagues and the
      feedback from students are synthesised with current literature regarding best
      teaching practices to develop these tips. RESULTS: These tips, ranging from
      involving students in the learning process to a routine practice of reflection
      after delivering a lecture, highlight methods of preparing and delivering
      lectures that follow the educational philosophy underpinning the PBL approach.
      CONCLUSION: We believe that these tips by advancing the driving force for
      meaningful learning will transform the didactic lectures of traditional
      curriculum to interactive sessions that would enhance understanding, augment
      critical thinking and promote self-directed learning among students.

PMID- 22364452
TI  - A model for programmatic assessment fit for purpose.
AB  - We propose a model for programmatic assessment in action, which simultaneously
      optimises assessment for learning and assessment for decision making about
      learner progress. This model is based on a set of assessment principles that are
      interpreted from empirical research. It specifies cycles of training, assessment
      and learner support activities that are complemented by intermediate and final
      moments of evaluation on aggregated assessment data points. A key principle is
      that individual data points are maximised for learning and feedback value,
      whereas high-stake decisions are based on the aggregation of many data points.
      Expert judgement plays an important role in the programme. Fundamental is the
      notion of sampling and bias reduction to deal with the inevitable subjectivity of
      this type of judgement. Bias reduction is further sought in procedural assessment
      strategies derived from criteria for qualitative research. We discuss a number of
      challenges and opportunities around the proposed model. One of its prime virtues
      is that it enables assessment to move, beyond the dominant psychometric discourse
      with its focus on individual instruments, towards a systems approach to
      assessment design underpinned by empirically grounded theory.

PMID- 22364453
TI  - Evidence within a portfolio-based assessment program: what do medical students
      select to document their performance?
AB  - BACKGROUND: Decisions about performance in programs of assessment that provide an
      array of assessment evidence require judgments about the quality of different
      pieces of assessment data to determine which combination of data points best
      represent a trainee's overall performance. AIM: In this article, we examine the
      nature of evidence selected by first-year medical students to include in a
      portfolio used to make promotion decisions. METHODS: We reviewed portfolios to
      examine the number, type, and source of assessments selected by students (n = 32)
      to document their performance in seven competencies. The quality of assessment
      data selected for each competency was rated by promotion committee members (n =
      14). RESULTS: Findings indicate that students cited multiple types and sources of
      available assessments. The promotion committee rated evidence quality highest for
      competencies where the program provided sufficient evidence for students to cite
      a broad range of assessments. When assessments were not provided by the program,
      students cited self-generated evidence. CONCLUSION: We found that when student
      constructed portfolios are part of an overall assessment system, students
      generally select evidence in proportion to the number and types of assessments
      available.

PMID- 22364454
TI  - Student perspectives on assessment: experience in a competency-based portfolio
      system.
AB  - Despite considerable evidence recognizing the importance of learners' perceptions
      of the assessment process, there is little literature depicting the participants'
      experience. We aim to capture these perceptions in order to gain insights into
      the strengths and weaknesses of a competency-based assessment system. Cleveland
      Clinic Lerner College of Medicine has implemented a learner-centered portfolio
      assessment system built around competency standards and continuous formative
      feedback. Promotion of students is based upon their feedback-supported portfolio
      essays, but feedback itself is individualized and formative in nature under the
      umbrella of the competencies. Importantly, there are no grades or ranking awarded
      for the competencies or at promotion. Four students share personal reflections of
      their experience to illuminate themes from the subjective experience of the
      learner and to understand how to align the learners' interests with the
      requirements of an assessment program.

PMID- 22364455
TI  - The use of programmatic assessment in the clinical workplace: a Maastricht case
      report.
AB  - The differences of learning experiences in the workplace put challenges on the
      assessment: the assessment programme should be aligned with the general
      competency framework of the curriculum and also fit to the differences in
      learning contexts of the workplace. We used van der Vleuten's programmatic
      assessment model to develop a workplace-based assessment programme for final year
      clerkships. We aimed to design a programme that stimulates learning, supports
      assessment decision, is feasible and non-bureaucratic. The first experiences with
      the programme show that students think that the programme has high learning value
      and the assessment is sufficiently robust. Many of the commonly reported
      weaknesses of work-based assessment (not a good fit with the educational context,
      too complex, too bureaucratic and too much work) were not mentioned by the
      students.

PMID- 22364456
TI  - A global template for reforming residency without work-hours restrictions:
      decrease caseloads, increase education. Findings of the Japan Resident Workload
      Study Group.
AB  - BACKGROUND: Japanese physician training programs are currently not subject to
      rigorous national standardization. Despite residency restructuring in 2004,
      little is known about the current work allocation of residents in Japan. AIMS: We
      quantified the amount of time that Japanese junior residents spend in service
      versus education in the context of caseload, fatigue, and low-value
      administrative work. METHODS: In this prospective, time-and-motion study, the
      activity of 1st- and 2nd-year residents at three Japanese community hospitals was
      observed at 5-min intervals over 1 week, and categorized as patient care,
      academic, non-patient care, and personal. Self-reported sleep data and caseload
      information were simultaneously collected. Data were subanalyzed by gender,
      training level, hospital, and shift. RESULTS: A total of 64 participating
      residents spent substantially more time in patient care activities than education
      (59.5% vs. 6.8%), and little time on low-value, non-patient work (5.1%).
      Residents reported a median 5 h of sleep before shifts and excessive sleepiness
      (median Epworth score, 12). Large variations in caseload were reported (median 10
      patients, range 0-60). CONCLUSIONS: New physicians in Japan deliver a large
      volume of high-value patient care, while receiving little structured education
      and enduring substantial sleep deprivation. In programs without work-hour
      restrictions, caseload limits may improve safety and quality.

PMID- 22364457
TI  - Can achievement emotions be used to better understand motivation, learning, and
      performance in medical education?
AB  - In this article, we consider an emergent theory of human emotion. The overarching
      purpose of the article is to introduce medical education researchers to the
      notion of achievement emotions and provide a brief overview of how this work can
      inform the theory, research, and practice of medical education. First, we define
      achievement emotions and describe one of the leading contemporary theories of
      achievement emotions, control-value theory (Pekrun R. 2006. The control-value
      theory of achievement emotions: Assumptions, corollaries, and implications for
      educational research and practice. Educ Psychol Rev 18:315-341.). Next, we
      distinguish between different types of achievement emotions, their proximal
      causes, and their consequences for motivation, learning, and performance, and we
      discuss several implications for educational practice. Finally, we end with a
      call for more research on achievement emotions in medical education to facilitate
      our understanding of emotions and their impact on important educational outcomes.

PMID- 22364458
TI  - Post-examination interpretation of objective test data: monitoring and improving
      the quality of high-stakes examinations--a commentary on two AMEE Guides.
AB  - As great emphasis is rightly placed upon the importance of assessment to judge
      the quality of our future healthcare professionals, it is appropriate not only to
      choose the most appropriate assessment method, but to continually monitor the
      quality of the tests themselves, in a hope that we may continually improve the
      process. This article stresses the importance of quality control mechanisms in
      the exam cycle and briefly outlines some of the key psychometric concepts
      including reliability measures, factor analysis, generalisability theory and item
      response theory. The importance of such analyses for the standard setting
      procedures is emphasised. This article also accompanies two new AMEE Guides in
      Medical Education (Tavakol M, Dennick R. Post-examination Analysis of Objective
      Tests: AMEE Guide No. 54 and Tavakol M, Dennick R. 2012. Post examination
      analysis of objective test data: Monitoring and improving the quality of high
      stakes examinations: AMEE Guide No. 66) which provide the reader with practical
      examples of analysis and interpretation, in order to help develop valid and
      reliable tests.

PMID- 22364459
TI  - Fit for practice: are we there yet?

PMID- 22364460
TI  - Workplace-based assessments: the emphasis on formative assessment.

PMID- 22364461
TI  - Low medical student publishing rates: lack or opportunity or initiative?

PMID- 22364462
TI  - Medical students' attitudes towards treating patients with HIV: a 12-year follow
      up study.

PMID- 22364463
TI  - Why teach medical students aspects of the respiratory examination that do not aid
      in diagnosis?

PMID- 22364464
TI  - Thirteenth tip for teaching expertise in clinical reasoning.

PMID- 22364465
TI  - Medical students' perceptions of learning reflective skills.

PMID- 22364466
TI  - Let the patient teach: patient feedback will help prepare medical students for
      the changing healthcare world.

PMID- 22364467
TI  - Successive objective long-case assessment as a driver of clerkship learning-
      evaluation through perception questionnaire.

PMID- 22364468
TI  - Clinically oriented laboratory illuminates challenging respiratory concepts to
      the pre-clinical medical students.

PMID- 22364469
TI  - The use of peer-assisted learning in medical education.

PMID- 22364470
TI  - eMedical Teacher.

PMID- 22364472
TI  - Control-value theory: using achievement emotions to improve understanding of
      motivation, learning, and performance in medical education: AMEE Guide No. 64.
AB  - In this AMEE Guide, we consider the emergent theoretical and empirical work on
      human emotion and how this work can inform the theory, research, and practice of
      medical education. In the Guide, we define emotion, in general, and achievement
      emotions, more specifically. We describe one of the leading contemporary theories
      of achievement emotions, control-value theory (Pekrun 2006), and we distinguish
      between different types of achievement emotions, their proximal antecedents, and
      their consequences for motivation, learning, and performance. Next, we review the
      empirical support for control-value theory from non-medical fields and suggest
      several important implications for educational practice. In this section, we
      highlight the importance of designing learning environments that foster a high
      degree of control and value for students. Finally, we end with a discussion of
      the need for more research on achievement emotions in medical education, and we
      propose several key research questions we believe will facilitate our
      understanding of achievement emotions and their impact on important educational
      outcomes.

PMID- 22364473
TI  - Post-examination interpretation of objective test data: monitoring and improving
      the quality of high-stakes examinations: AMEE Guide No. 66.
AB  - The purpose of this Guide is to provide both logical and empirical evidence for
      medical teachers to improve their objective tests by appropriate interpretation
      of post-examination analysis. This requires a description and explanation of some
      basic statistical and psychometric concepts derived from both Classical Test
      Theory (CTT) and Item Response Theory (IRT) such as: descriptive statistics,
      explanatory and confirmatory factor analysis, Generalisability Theory and Rasch
      modelling. CTT is concerned with the overall reliability of a test whereas IRT
      can be used to identify the behaviour of individual test items and how they
      interact with individual student abilities. We have provided the reader with
      practical examples clarifying the use of these frameworks in test development and
      for research purposes.

PMID- 22364474
TI  - Innovations in applied health: evaluating a simulation-enhanced,
      interprofessional curriculum.
AB  - BACKGROUND: In response to current trends in healthcare education, teachers at
      the Michener Institute for Applied Health Sciences implemented a New Curriculum
      Model (NCM) in 2006, building a curriculum to better transition students from
      didactic to clinical education. Through the implementation of interprofessional
      education and simulated clinical scenarios, educators created a setting to
      develop, contextualize and apply students' skills before entry to the clinical
      environment. AIMS: In this pilot study, researchers assessed the impact of the
      NCM intervention on student preparedness for clinical practicum. METHODS: A mixed
      methods evaluation was conducted, collecting survey assessments and qualitative
      focus group feedback from clinical educators and students. RESULTS: Clinical
      educators identified Michener NCM students to be significantly better prepared
      for clinical practicum when compared to previous cohorts (p < 0.05%). Students
      also noted significant improvements as implementation issues were resolved from
      years one to two of the NCM. CONCLUSIONS: The infusion of simulation and
      interprofessional education into Michener's applied health curricula resulted in
      a significant improvement in clinical preparedness. The Michener NCM bridged the
      gap previously separating didactic education and clinical practice, transitioning
      applied health students from trained technicians to more complete health care
      professionals.

PMID- 22364475
TI  - Reaching the limits of mandated self-reporting: clinical logbooks do not predict
      clerkship performance.
AB  - BACKGROUND: Logbooks are used by US medical schools to evaluate curricular
      objectives and meet accreditation requirements, but research supporting their
      utility is conflicting. AIMS: The goal of our study was to examine the
      relationship between volume of clinical rotation experiences as reported in a
      logbook and clerkship grades within a longitudinal integrated clerkship. METHODS:
      We conducted a retrospective cohort study of third-year (clinical) medical
      students during academic year 2008-2009. We tracked student entries in a pocket
      sized logbook (number of clinical encounters per clerkship, total number of
      exams, and procedures over the academic year). We performed correlation analyses
      between logbook entries and clerkship grades. RESULTS: We enrolled 36 students,
      who reported a total of 2992 encounters, 2262 exams, and 2342 procedures.
      Correlation coefficients between volume of clinical experience and clerkship
      grades were less than 0.4, indicating low correlation. We found borderline
      statistical significance for the Neurology, OB/Gyn, and Surgery clerkships.
      Sensitivity analyses showed little correlation between low-reporting activity and
      clerkship grades. CONCLUSIONS: Even within an integrated longitudinal clerkship
      framework, our findings are consistent with previous studies showing a negligible
      relationship between logbooks as an educational process measure and how they
      relate to educational outcomes.

PMID- 22364476
TI  - Medical students as teachers at CoSMO, Columbia University's student-run clinic:
      a pilot study and literature review.
AB  - BACKGROUND: Although medical students are expected to teach as soon as they begin
      residency, medical schools have just recently begun adding teacher training to
      their curricula. Student-run clinics (SRCs) may provide opportunities in clinical
      teaching before residency. AIM: The aim of this pilot study was to examine
      students' experiences in clinical teaching at Columbia Student Medical Outreach
      (CoSMO), Columbia University's SRC, during the 2009-2010 school year. METHODS: A
      mixed-methods approach was used. Data included closed and open-ended surveys (n =
      34), combined interviews with preclinical and clinical student pairs (n = 5),
      individual interviews (n = 10), and focus groups (n = 3). The transcripts were
      analyzed using the principles of grounded theory. RESULTS: Many students had
      their first clinical teaching experience while volunteering at CoSMO. Clinical
      students' ability to teach affected the quality of the learning experience for
      their preclinical peers. Preclinical students who asked questions and engaged in
      patient care challenged their clinical peers to balance teaching with patient
      care. Clinical students began to see themselves as teachers while volunteering at
      CoSMO. CONCLUSION: The practical experiences in clinical teaching that students
      have at SRCs can supplement classroom-based trainings. Medical schools might
      revisit their SRCs as places for exposure to clinical teaching.

PMID- 22364477
TI  - Comparing three experiential learning methods and their effect on medical
      students' attitudes to learning communication skills.
AB  - BACKGROUND: Despite numerous studies exploring medical students' attitudes to
      communication skills learning (CSL), there are apparently no studies comparing
      different experiential learning methods and their influence on students'
      attitudes. AIMS: We compared medical students' attitudes to learning
      communication skills before and after a communication course in the data as a
      whole, by gender and when divided into three groups using different methods.
      METHOD: Second-year medical students (n = 129) were randomly assigned to three
      groups. In group A (n = 42) the theatre in education method, in group B (n = 44)
      simulated patients and in group C (n = 43) role-play were used. The data were
      gathered before and after the course using Communication Skills Attitude Scale.
      RESULTS: Students' positive attitudes to learning communication skills (PAS;
      positive attitude scale) increased significantly and their negative attitudes
      (NAS; negative attitude scale) decreased significantly between the beginning and
      end of the course. Female students had more positive attitudes than the male
      students. There were no significant differences in the three groups in the mean
      scores for PAS or NAS measured before or after the course. CONCLUSIONS: The use
      of experiential methods and integrating communication skills training with visits
      to health centres may help medical students to appreciate the importance of CSL.

PMID- 22364478
TI  - Who am I? Key influences on the formation of academic identity within a faculty
      development program.
AB  - INTRODUCTION: Professional identity encompasses how individuals understand
      themselves, interpret experiences, present themselves, wish to be perceived, and
      are recognized by the broader professional community. For health professional and
      health science educators, their 'academic' professional identity is situated
      within their academic community and plays an integral role in their well being
      and productivity. This study aims to explore factors that contribute to the
      formation and growth of academic identity (AI) within the context of a
      longitudinal faculty development program. METHODS: Using a qualitative case study
      approach, data from three cohorts of a 2-year faculty development program were
      explored and analyzed for emerging issues and themes related to AI. RESULTS:
      Factors salient to the formation of AI were grouped into three major domains:
      personal (cognitive and emotional factors unique to each individual); relational
      (connections and interactions with others); and contextual (the program itself
      and external work environments). DISCUSSION: Faculty development initiatives not
      only aim to develop knowledge, skills, and attitudes, but also contribute to the
      formation of academic identities in a number of different ways. Facilitating the
      growth of AI has the potential to increase faculty motivation, satisfaction, and
      productivity. Faculty developers need to be mindful of factors within the
      personal, relational, and contextual domains when considering issues of program
      design and implementation.

PMID- 22364479
TI  - Incidence of metachronous second primary cancers in Osaka, Japan: update of
      analyses using population-based cancer registry data.
AB  - Cancer survivors are at excess risk of developing second primary cancers, but the
      precise level of risk in Japanese patients is not known. To investigate the risk
      of survivors developing second primary cancers, we conducted a retrospective
      cohort study using data from the Osaka Cancer Registry. The study subjects
      comprised all reported patients aged 0-79 years who were first diagnosed with
      cancer between 1985 and 2004 in Osaka and who survived for at least 3 months,
      followed-up through to December 2005. A metachronous second primary cancer was
      defined as any invasive second cancer that was diagnosed between 3 months and 10
      years after the first cancer diagnosis. The main outcome measures were incidence
      rates per 100,000 person-years, cumulative risk and standardized incidence ratios
      (SIR) of second primary cancer. Metachronous second primary cancers developed in
      13,385 of 355,966 survivors (3.8%) after a median follow-up of 2.5 years. Sex
      specific incidence rates of metachronous second primary cancer per 100,000 person
      years increased with age, and were higher among men than women (except for the 0
      49 years age group), but these rates did not differ over the study period. The 10
      year cumulative risk was estimated as 13.0% for those who first developed cancer
      at 60-69 years of age (16.2% for men, 8.6% for women). The SIR among those with
      first cancer diagnosed at 0-39 and 40-49 years of age were 2.13 and 1.52,
      respectively, in both sexes, whereas the SIR among cancers of the mouth/pharynx,
      esophagus and larynx were much higher than one as for site relationships. We
      showed that cancer survivors in Osaka, Japan, were at higher risk of second
      primary cancers compared with the general population. Our findings indicate that
      second primary cancers should be considered as a commonly encountered major
      medical problem. Further investigations are required to advance our understanding
      to enable the development of effective measures against multiple primary cancers.

PMID- 22364480
TI  - Cu-promoted [2 + 2] cycloaddition of 1,4-bisallenes.
AB  - The thermal reaction of 1,4-bisallenes with the aid of Cu salt/amine
      significantly suppressed the formal [3,3] sigmatropic rearrangement resulting in
      the highly selective formation of the bicyclo[4.2.0]octadiene framework. This
      reaction could be applied to the one-pot synthesis of bicyclo[4.2.0]octadienes
      from 1,5-hexadiynes via the Crabbe homologation.

PMID- 22364481
TI  - Correlation of oil-water and air-water contact angles of diverse silanized
      surfaces and relationship to fluid interfacial tensions.
AB  - The use of air-water, theta(wa), or air-liquid contact angles is customary in
      surface science, while oil-water contact angles, theta(ow), are of paramount
      importance in subsurface multiphase flow phenomena including petroleum recovery,
      nonaqueous phase liquid fate and transport, and geological carbon sequestration.
      In this paper we determine both the air-water and oil-water contact angles of
      silica surfaces modified with a diverse selection of silanes, using hexadecane as
      the oil. The silanes included alkylsilanes, alkylarylsilanes, and silanes with
      alkyl or aryl groups that are functionalized with heteroatoms such as N, O, and
      S. These silanes yielded surfaces with wettabilities from water wet to oil wet,
      including specific silanized surfaces functionalized with heteroatoms that yield
      intermediate wet surfaces. The oil-water contact angles for clean and silanized
      surfaces, excluding one partially fluorinated surface, correlate linearly with
      air-water contact angles with a slope of 1.41 (R = 0.981, n = 13). These data
      were used to examine a previously untested theoretical treatment relating air
      water and oil-water contact angles in terms of fluid interfacial energies.
      Plotting the cosines of these contact angles against one another, we obtain the
      relationship cos theta(wa) = 0.667 cos theta(ow) + 0.384 (R = 0.981, n = 13),
      intercepting cos theta(ow) = -1 at -0.284, which is in excellent agreement with
      the linear assumption of the theory. The theoretical slope, based on the fluid
      interfacial tensions sigma(wa), sigma(ow), and sigma(oa), is 0.67. We also
      demonstrate how silanes can be used to alter the wettability of the interior of a
      pore network micromodel device constructed in silicon/silica with a glass cover
      plate. Such micromodels are used to study multiphase flow phenomena. The contact
      angle of the resulting interior was determined in situ. An intermediate wet
      micromodel gave a contact angle in excellent agreement with that obtained on an
      open planar silica surface using the same silane.

PMID- 22364482
TI  - DOPA-mediated reduction allows the facile synthesis of fluorescent gold
      nanoclusters for use as sensing probes for ferric ions.
AB  - In this paper, we describe a simple one-pot method, employing l-3,4
      dihydroxyphenylalanine (L-DOPA) as a reducing/capping reagent, for the synthesis
      of fluorescent gold nanoclusters (AuNCs). Within a short reaction time of 15 min
      (excluding the time required for purification), this strategy allows the
      fabrication of homogeneous AuNCs having the capability to sense ferric ions
      (Fe(3+)). The as-prepared AuNCs exhibited a fluorescence emission at 525 nm and a
      quantum yield of 1.7%. On the basis of an aggregation-induced fluorescence
      quenching mechanism, these fluorescent AuNCs offer acceptable sensitivity, high
      selectivity, and a limit of detection of 3.5 MUM for the determination of Fe(3+)
      ions, which is lower than the maximum level (0.3 mg L(-1), equivalent to 5.4 MUM)
      of Fe(3+) permitted in drinking water by the U.S. Environmental Protection
      Agency.

PMID- 22364483
TI  - Epoxy pipe relining - an emerging contact allergy risk for workers.
AB  - BACKGROUND: Epoxy pipe relining is a method of repairing old and worn water pipes
      supplying households. The method, using epoxy resin systems (ERSs), involves
      creating a new pipe inside an existing pipe. Large amounts of epoxy are normally
      handled at small, temporary worksites. OBJECTIVES: To describe working conditions
      and contact allergies to ERSs in 8 patients with occupational contact dermatitis
      related to their work in the relining trade. METHODS: Eight patients with
      suspected work-related eczema in the relining trade were referred to our
      Occupational and Environmental Dermatology outpatient unit. They were examined
      and patch-tested between August 2010 and May 2011. RESULTS: Seven patients were
      patch test-positive to ERSs, and 6 of 8 reacted to the epoxy resin (MW 340) in
      the baseline series. Five of the patients were patch test-positive to their own
      work products. Seven of the cases had to leave the relining trade because of skin
      problems. CONCLUSIONS: Relining is a widely used alternative to replacing old
      pipes, and entails a risk of massive skin exposure to ERSs and consequently a
      high risk of developing allergic contact dermatitis. Further mapping of working
      methods and use of personal protective equipment (PPE) is crucial to reduce
      hazardous skin exposure.

PMID- 22364484
TI  - A modified provisional stenting approach to coronary bifurcation lesions:
      clinical application of the "jailed-balloon technique".
AB  - OBJECTIVES: To demonstrate the application of a novel provisional side branch
      (SB) stenting strategy for coronary bifurcation lesions using a "jailed-balloon"
      technique (JBT). BACKGROUND: Adverse cardiac events are higher for percutaneous
      coronary intervention (PCI) of bifurcation lesions. Recent studies support the
      use of provisional SB stenting, but a risk of SB closure and a higher rate of
      target lesion revascularization (TLR) remain important limitations. METHODS: From
      December 2007 to August 2010, 100 patients with 102 bifurcation lesions underwent
      PCI using the JBT. Baseline and postprocedural quantitative coronary angiography
      (QCA) analysis were performed. Procedural and immediate clinical outcomes were
      reviewed. RESULTS: The majority of patients presented with acute coronary
      syndrome (68%) and had Medina class 1,1,1 bifurcation lesions (91%). TIMI 3 flow
      was established in 100% of main branch and 99% of SB lesions. QCA revealed
      preservation of the bifurcation angle after PCI (pre-PCI: 59.6 +/- 30.0; post
      PCI: 63.3 +/- 26.8, P = 0.41). Nine patients (9%) had lesions that required
      rewiring and two patients (2%) required provisional stenting of the SB. SB loss
      occurred in one patient (1%). The jailed-balloon or wire was not entrapped during
      any PCI. One patient (1%) suffered a periprocedural myocardial infarction (MI).
      CONCLUSIONS: Provisional stenting of complex coronary bifurcation lesions using a
      JBT is associated with a high procedural success rate, improved SB patency, and a
      low rate of immediate cardiac events. Further study is warranted to evaluate the
      role of JBT in improving long-term clinical outcomes in PCI of complex
      bifurcation lesions.

PMID- 22364485
TI  - Functional coupling of sensorimotor and associative areas during a catching ball
      task: a qEEG coherence study.
AB  - BACKGROUND: Catching an object is a complex movement that involves not only
      programming but also effective motor coordination. Such behavior is related to
      the activation and recruitment of cortical regions that participates in the
      sensorimotor integration process. This study aimed to elucidate the cortical
      mechanisms involved in anticipatory actions when performing a task of catching an
      object in free fall. METHODS: Quantitative electroencephalography (qEEG) was
      recorded using a 20-channel EEG system in 20 healthy right-handed participants
      performed the catching ball task. We used the EEG coherence analysis to
      investigate subdivisions of alpha (8-12 Hz) and beta (12-30 Hz) bands, which are
      related to cognitive processing and sensory-motor integration. RESULTS:
      Notwithstanding, we found the main effects for the factor block; for alpha-1,
      coherence decreased from the first to sixth block, and the opposite effect
      occurred for alpha-2 and beta-2, with coherence increasing along the blocks.
      CONCLUSION: It was concluded that to perform successfully our task, which
      involved anticipatory processes (i.e. feedback mechanisms), subjects exhibited a
      great involvement of sensory-motor and associative areas, possibly due to
      organization of information to process visuospatial parameters and further catch
      the falling object.

PMID- 22364489
TI  - Motor performance improved by exercises in cerebral ischemic rats.
AB  - Physical exercise may induce neuroprotective effects against brain damage after
      stroke. The authors aimed to investigate the effects of various exercises on
      motor function, striatal angiogenesis, and infarct volume in cerebral ischemic
      rats. Adult male Sprague Dawley rats were subjected to middle cerebral artery
      occlusion and randomly assigned to 1 of the 4 groups: Rota-rod training, lower
      speed treadmill training, higher speed treadmill training, or no exercise
      control. Motor function, striatal angiogenesis, and infarct volume were evaluated
      before or after motor training. After training, motor function and striatal
      angiogenesis changed significantly in Rota-rod and higher speed treadmill
      training groups as compared with the control group. Improvement in motor function
      significantly correlated with striatal angiogenesis after motor training. Infarct
      volumes were significantly decreased in lower and higher speed treadmill training
      groups. The results indicated that both motor training procedures can be used as
      effective training programs in stroke rehabilitation.

PMID- 22364487
TI  - Tribal casinos in California: the last vestige of indoor smoking.
AB  - BACKGROUND: High levels of airborne particles from secondhand smoke have been
      reported in California Indian casinos. Yet, little is known regarding the smoking
      status of casino patrons, their avoidance of secondhand smoke while visiting, and
      their views on a hypothetical smoking ban. METHODS: Predictors of visiting an
      Indian casino were assessed among participants of the 2008 California Tobacco
      Survey (n = 10,397). Exposure to and avoidance of secondhand smoke were
      subsequently analyzed among a subset of participants who had visited a casino in
      the year prior to the survey (n = 3,361). RESULTS: Ethnic minorities, older
      individuals, current smokers and residents of sparsely populated regions of
      California were more likely than other demographic groups to visit a tribal
      casino. Avoidance of secondhand smoke was more frequent among the never smokers
      than former and current smokers, particularly those who last visited a casino
      lacking physical separation between non-smoking and smoking sections. The never
      smokers versus current smokers disproportionately expressed a willingness to
      extend their stay and visit again if smoking were prohibited. CONCLUSIONS: If
      casinos became smoke free, then it is anticipated that they would be visited by a
      significantly larger number of Californians, including both patrons and those who
      otherwise would not have visited a casino.

PMID- 22364490
TI  - Mercury in the spinal cord after inhalation of mercury.
AB  - Amyotrophic lateral sclerosis (ALS) affects anterior horn cells of the spinal
      cord causing an indolent slow and steady deterioration of muscle strength leading
      inevitably to death in respiratory failure. ALS is a model condition for
      neurodegenerative disorders. Exposure to different agents dispersed in the
      environment has been suggested to cause neurodegeneration but no convincing
      evidence for such a link has yet been presented. Respiratory exposure to metallic
      mercury (Hg(0)) from different sources may be suspected. Body distribution of
      metallic mercury is fast and depends on solubility properties. Routes of
      transport, metabolism, excretion and biological half-life determine the overall
      toxic effects. Inhalation experiments were performed in 1984 where small marmoset
      monkeys (Callithrix jacchus) were exposed to (203) Hg(0 vapour) mixed into the
      breathing air (4-5 MUg/l). After 1 hr of exposure, they were killed and whole
      body autoradiograms prepared to study the distribution of mercury within organs.
      Autoradiograms showed that Hg was deposited inside the spinal cord. Areas of
      enhanced accumulation anatomically corresponding to motor nuclei could be
      observed. This study describes a reinvestigation, with new emphasis on the spinal
      cord, of these classical metal exposure data in a primate, focusing on their
      relevance for the causation of neurodegenerative disorders. A comparison with
      more recent rodent experiments with similar findings is included. The hypothesis
      that long-time low-dose respiratory exposure to metals, for example, Hg,
      contributes to neurodegenerative disorders is forwarded and discussed.

PMID- 22364491
TI  - Seeking to shed some light on the binding of fluoroquinolones to albumins.
AB  - Interactions between serum albumins (HSA, human, and BSA, bovine) and
      fluoroquinolones (FQs), such as enoxacin, norfloxacin, ciprofloxacin, and
      ofloxacin, have been studied using the laser flash photolysis technique.
      Lifetimes and quantum yields of FQs triplet excited states ((3)FQs) are not
      affected by the presence of albumins, however, the quenching of (3)FQs by
      tryptophan and tyrosine and the subsequent generation of FQs radical anions and
      tyrosyl or tryptophanyl radicals were detected. These results, besides agreeing
      with association constants (K(a)) for FQs binding to albumins lower than 6 *
      10(2) M(-1), are highly relevant to understanding the process of photohapten
      formation, the first event in the onset of photoallergy. The emission of
      tryptophan within albumin is not affected by the presence of FQs when the inner
      filter effects (IFE) of these drugs are taken into account, which explains the
      discrepancies reported in the literature about K(a) of FQs with albumins.

PMID- 22364492
TI  - Method for the validation of intraspecific crosses of  Saccharomyces cerevisiae 
      strains by minisatellite analysis.
AB  - The crossing of  Saccharomyces  strains by spore conjugation is one of the ways
      to obtain new starter cultures for the fermentation industry. One of the major
      difficulties of this practice is the identification of the newly formed hybrids.
      In this work we describe an effective molecular method for the validation of
      Saccharomyces intraspecific crosses. The method described is based in the
      hypothesis that hybrids constructed by spore conjugation contain the sum of the
      genomes of both parental strains. As a consequence, the conjugation of spores of
      two yeasts showing different genomic fingerprinting profiles will result in a
      hybrid culture that will show the sum of both profiles. We demonstrated that the
      detection of polymorphism in two genes containing minisatellite-like sequences,
      either SED1 or AGA1, is suitable for this purpose. Using this strategy we were
      able to validate 15 crosses out of 162 hybridization attempts.

PMID- 22364494
TI  - Dynamic changes in the gene expression of zebrafish Reelin receptors during
      embryogenesis and hatching period.
AB  - The brain morphology of vertebrates exhibits huge evolutionary diversity, but one
      of the shared morphological features unique to vertebrate brain is laminar
      organization of neurons. Because the Reelin signal plays important roles in the
      development of the laminar structures in mammalian brain, investigation of Reelin
      signal in lower vertebrates will give some insights into evolution of vertebrate
      brain morphogenesis. Although zebrafish homologues of Reelin, the ligand, and
      Dab1, a cytoplasmic component of the signaling pathway, have been reported, the
      Reelin receptor molecules of zebrafish are not reported yet. Here, we sought cDNA
      sequence of zebrafish homologue of the receptors, vldlr and apoer2, and examined
      their expression patterns by in situ hybridization. Developmental gene expression
      pattern of reelin, dab1, vldlr, and apoer2 in the central nervous system of
      zebrafish was compared, and their remarkable expression was detected in the
      developing laminar structures, such as the tectum and the cerebellum, and also
      non-laminated structures, such as the pallium. The Reelin receptors exhibited
      different spatial and temporal gene expression. These results suggest a
      possibility that duplication and subsequent functional diversity of Reelin
      receptors contributed to the morphological and functional evolution of vertebrate
      brain.

PMID- 22364493
TI  - Inverse-phosphocholine lipids: a remix of a common phospholipid.
AB  - Zwitterionic inverse-phosphocholine (iPC) lipids contain headgroups with an
      inverted charge orientation relative to phosphocholine (PC) lipids. The iPC lipid
      headgroup has a quaternary amine adjacent to the bilayer interface and a
      phosphate that extends into the aqueous phase. Neutral iPC lipids with ethylated
      phosphate groups (CPe) and anionic iPC lipids nonethylated phosphate groups (CP)
      were synthesized. The surface potential of CPe liposomes remains negative across
      a broad pH range and in the presence of up to 10 mM Ca(2+). CP liposomes
      aggregate in the presence of Ca(2+), but at a slower rate than other anionic
      lipids. Hydrolysis of CP lipids by alkaline phosphatases generates a cationic
      lipid. CPe liposomes release encapsulated anionic carboxyfluorescein (CF) 20
      times faster than PC liposomes and release uncharged glucose twice as fast as PC
      liposomes.  As such,  iPC lipids afford a unique opportunity to investigate the
      biophysical and bioactivity-related ramifications of a charge inversion at the
      bilayer surface.

PMID- 22364495
TI  - Shenfushu granule and atropine attenuate microvasculature loss in rat models with
      5/6 nephrectomy.
AB  - OBJECTIVE: To investigate the effect of Shenfushu granule (SFSG) and atropine
      treatment on microvessels of the kidney and intestine after chronic renal failure
      (CRF) induced by 5/6 nephrectomy. METHODS: Sprague Dawley rats were randomly
      divided into a sham group, a model group, an SFSG group, and an SFSG + atropine
      group. SFSG was administered daily 1 week after inducing CRF. Rats were
      sacrificed at the end of the eighth week. Urinary protein and stool and serum
      urea nitrogen (UN) and creatinine (Cr) levels were assessed. Hematoxylin and
      eosin and periodic acid-Schiff staining of the kidney and examination of the
      vascular endothelial growth factor (VEGF) and microvessel density (MVD) levels in
      kidney and intestine were performed. RESULTS: The Cr and UN levels were
      significantly increased in blood and stool of the model group. SFSG significantly
      improved renal function, and the protective effects were further enhanced with
      the addition of atropine. Glomerular sclerosis, tubulointerstitial fibrosis, and
      microvessel loss were observed in CRF rats, and these pathological changes were
      ameliorated in the two treatment groups (p < 0.05), especially in the SFSG +
      atropine group. The expression of VEGF and MVD was decreased in the CRF rats
      compared with the sham group. SFSG treatment increased the expression of these
      proteins and reversed the degree of microvessel loss, glomerular sclerosis, and
      tubulointerstitial fibrosis (p < 0.05). Co-treatment with atropine enhanced these
      effects. CONCLUSIONS: SFSG alleviated renal function, upregulated the expression
      of VEGF and MVD in the kidney and intestine, and attenuated the degree of
      microvessel loss, glomerular sclerosis, and tubulointerstitial fibrosis in the
      early stages of CRF in rats, and addition of atropine enhanced these effects.

PMID- 22364496
TI  - Living with coeliac disease: survey results from the U.S.A.
AB  - BACKGROUND: The only treatment for coeliac disease is lifelong adherence to a
      rigorous gluten-free diet. The present study aimed to evaluate the influence of
      coeliac disease on the social aspects of daily life of individuals in the U.S.A.
      METHODS: The present study used a self-administered survey including the standard
      Quality of Life questionnaire (12-item short-form) with validated disease
      specific questions. sas statistical software 2010 (SAS Institute, Cary, NC,
      U.S.A.) was used to calculate the mean (SD). RESULTS: Individuals with coeliac
      disease overall had a low positive health perception. Validated diet and disease
      specific questions revealed a significant negative impact on quality of life in
      social settings. Specifically, the areas of travel, dining out and family life
      are most affected. The negative impact of diet significantly decreased over time,
      although it did not resolve for the domains of dining out of the home and travel.
      Those diagnosed in childhood and maintained on the diet had less of an impact on
      the quality of life as an adult. CONCLUSIONS: Individuals with coeliac disease in
      the U.S.A. have a diminished quality of life, especially in the social aspects of
      life.

PMID- 22364497
TI  - Potentials of a ten dollar pre-paid public health plan for rural health in Sub
      Saharan Africa.

PMID- 22364498
TI  - The neural representation of time: an information-theoretic perspective.
AB  - A prominent finding in psychophysical experiments on time perception is Weber's
      law, the linear scaling of timing errors with duration. The ability to reproduce
      this scaling has been taken as a criterion for the validity of neurocomputational
      models of time perception. However, the origin of Weber's law remains unknown,
      and currently only a few models generically reproduce it. Here, we use an
      information-theoretical framework that considers the neuronal mechanisms of time
      perception as stochastic processes to investigate the statistical origin of
      Weber's law in time perception and also its frequently observed deviations. Under
      the assumption that the brain is able to compute optimal estimates of time, we
      find that Weber's law only holds exactly if the estimate is based on temporal
      changes in the variance of the process. In contrast, the timing errors scale
      sublinearly with time if the systematic changes in the mean of a process are used
      for estimation, as is the case in the majority of time perception models, while
      estimates based on temporal correlations result in a superlinear scaling. This
      hierarchy of temporal information is preserved if several sources of temporal
      information are available. Furthermore, we consider the case of multiple
      stochastic processes and study the examples of a covariance-based model and a
      model based on synfire chains. This approach reveals that existing
      neurocomputational models of time perception can be classified as mean-, variance
      and correlation-based processes and allows predictions about the scaling of the
      resulting timing errors.

PMID- 22364499
TI  - Markov chain Monte Carlo methods for state-space models with point process
      observations.
AB  - This letter considers how a number of modern Markov chain Monte Carlo (MCMC)
      methods can be applied for parameter estimation and inference in state-space
      models with point process observations. We quantified the efficiencies of these
      MCMC methods on synthetic data, and our results suggest that the Reimannian
      manifold Hamiltonian Monte Carlo method offers the best performance. We further
      compared such a method with a previously tested variational Bayes method on two
      experimental data sets. Results indicate similar performance on the large data
      sets and superior performance on small ones. The work offers an extensive suite
      of MCMC algorithms evaluated on an important class of models for physiological
      signal analysis.

PMID- 22364500
TI  - The successor representation and temporal context.
AB  - The successor representation was introduced into reinforcement learning by Dayan
      ( 1993 ) as a means of facilitating generalization between states with similar
      successors. Although reinforcement learning in general has been used extensively
      as a model of psychological and neural processes, the psychological validity of
      the successor representation has yet to be explored. An interesting possibility
      is that the successor representation can be used not only for reinforcement
      learning but for episodic learning as well. Our main contribution is to show that
      a variant of the temporal context model (TCM; Howard & Kahana,  2002 ), an
      influential model of episodic memory, can be understood as directly estimating
      the successor representation using the temporal difference learning algorithm
      (Sutton & Barto,  1998 ). This insight leads to a generalization of TCM and new
      experimental predictions. In addition to casting a new normative light on TCM,
      this equivalence suggests a previously unexplored point of contact between
      different learning systems.

PMID- 22364501
TI  - A proof of convergence of the concave-convex procedure using Zangwill's theory.
AB  - The concave-convex procedure (CCCP) is an iterative algorithm that solves d.c.
      (difference of convex functions) programs as a sequence of convex programs. In
      machine learning, CCCP is extensively used in many learning algorithms, including
      sparse support vector machines (SVMs), transductive SVMs, and sparse principal
      component analysis. Though CCCP is widely used in many applications, its
      convergence behavior has not gotten a lot of specific attention. Yuille and
      Rangarajan analyzed its convergence in their original paper; however, we believe
      the analysis is not complete. The convergence of CCCP can be derived from the
      convergence of the d.c. algorithm (DCA), proposed in the global optimization
      literature to solve general d.c. programs, whose proof relies on d.c. duality. In
      this note, we follow a different reasoning and show how Zangwill's global
      convergence theory of iterative algorithms provides a natural framework to prove
      the convergence of CCCP. This underlines Zangwill's theory as a powerful and
      general framework to deal with the convergence issues of iterative algorithms,
      after also being used to prove the convergence of algorithms like expectation
      maximization and generalized alternating minimization. In this note, we provide a
      rigorous analysis of the convergence of CCCP by addressing two questions: When
      does CCCP find a local minimum or a stationary point of the d.c. program under
      consideration? and when does the sequence generated by CCCP converge? We also
      present an open problem on the issue of local convergence of CCCP.

PMID- 22364502
TI  - On the relation between encoding and decoding of neuronal spikes.
AB  - Neural coding is a field of study that concerns how sensory information is
      represented in the brain by networks of neurons. The link between external
      stimulus and neural response can be studied from two parallel points of view. The
      first, neural encoding, refers to the mapping from stimulus to response. It
      focuses primarily on understanding how neurons respond to a wide variety of
      stimuli and constructing models that accurately describe the stimulus-response
      relationship. Neural decoding refers to the reverse mapping, from response to
      stimulus, where the challenge is to reconstruct a stimulus from the spikes it
      evokes. Since neuronal response is stochastic, a one-to-one mapping of stimuli
      into neural responses does not exist, causing a mismatch between the two
      viewpoints of neural coding. Here we use these two perspectives to investigate
      the question of what rate coding is, in the simple setting of a single stationary
      stimulus parameter and a single stationary spike train represented by a renewal
      process. We show that when rate codes are defined in terms of encoding, that is,
      the stimulus parameter is mapped onto the mean firing rate, the rate decoder
      given by spike counts or the sample mean does not always efficiently decode the
      rate codes, but it can improve efficiency in reading certain rate codes when
      correlations within a spike train are taken into account.

PMID- 22364503
TI  - Adaptive optimal control without weight transport.
AB  - Many neural control systems are at least roughly optimized, but how is optimal
      control learned? There are algorithms for this purpose, but in their current
      forms, they are not suited for biological neural networks because they rely on a
      type of communication that is not available in the brain, namely, weight
      transport-transmitting the strengths, or "weights," of individual synapses to
      other synapses and neurons. Here we show how optimal control can be learned
      without weight transport. Our method involves a set of simple mechanisms that can
      compensate for the absence of weight transport in the brain and so may be useful
      for neural computation generally.

PMID- 22364504
TI  - Analytical integrate-and-fire neuron models with conductance-based dynamics and
      realistic postsynaptic potential time course for event-driven simulation
      strategies.
AB  - In a previous paper (Rudolph & Destexhe, 2006), we proposed various models, the
      gIF neuron models, of analytical integrate-and-fire (IF) neurons with conductance
      based (COBA) dynamics for use in event-driven simulations. These models are based
      on an analytical approximation of the differential equation describing the IF
      neuron with exponential synaptic conductances and were successfully tested with
      respect to their response to random and oscillating inputs. Because they are
      analytical and mathematically simple, the gIF models are best suited for fast
      event-driven simulation strategies. However, the drawback of such models is they
      rely on a nonrealistic postsynaptic potential (PSP) time course, consisting of a
      discontinuous jump followed by a decay governed by the membrane time constant.
      Here, we address this limitation by conceiving an analytical approximation of the
      COBA IF neuron model with the full PSP time course. The subthreshold and
      suprathreshold response of this gIF4 model reproduces remarkably well the
      postsynaptic responses of the numerically solved passive membrane equation
      subject to conductance noise, while gaining at least two orders of magnitude in
      computational performance. Although the analytical structure of the gIF4 model is
      more complex than that of its predecessors due to the necessity of calculating
      future spike times, a simple and fast algorithmic implementation for use in large
      scale neural network simulations is proposed.

PMID- 22364506
TI  - Coatings of polyethylene glycol for suppressing adhesion between solid
      microspheres and flat surfaces.
AB  - This article describes the development and the examination of surface coatings
      that suppress the adhesion between glass surfaces and polymer microspheres.
      Superparamagnetic doping allowed for exerting magnetic forces on the microbeads.
      The carboxyl functionalization of the polymer provided the means for coating the
      beads with polyethylene glycol (PEG) with different molecular weight. Under
      gravitational force, the microbeads settled on glass surfaces with similar
      polymer coatings. We examined the efficacy of removing the beads from the glass
      surfaces by applying a pulling force of ~1.2 pN. The percent beads remaining on
      the surface after applying the pulling force for approximately 5 s served as an
      indication of the adhesion propensity. Coating of PEG with molecular weight
      ranging between 3 and 10 kDa was essential for suppressing the adhesion. For the
      particular substrates, surface chemistry and aqueous media we used, coatings of 5
      kDa manifested optimal suppression of adhesion: that is, only 3% of the
      microbeads remained on the surface after applying the pulling magnetic force.
      When either the glass or the beads were not PEGylated, the adhesion between them
      was substantial. Addition of a noncharged surfactant, TWEEN, above its critical
      micelle concentrations (CMCs) suppressed the adhesion between noncoated
      substrates. The extent of this surfactant-induced improvement of the adhesion
      suppression, however, did not exceed the quality of preventing the adhesion that
      we attained by PEGylating both substrates. In addition, the use of surfactants
      did not significantly improve the suppression of bead-surface adhesion when both
      substrates were PEGylated. These findings suggest that such surfactant additives
      tend to be redundant and that covalently grafted coatings of PEGs with selected
      chain lengths provide sufficient suppression of nonspecific interfacial
      interactions.

PMID- 22364508
TI  - Controlled ultraviolet (UV) photoinitiated fabrication of monolithic porous layer
      open tubular (monoPLOT) capillary columns for chromatographic applications.
AB  - An automated column fabrication technique that is based on a ultraviolet (UV)
      light-emitting diode (LED) array oven, and provides precisely controlled "in
      capillary" ultraviolet (UV) initiated polymerization at 365 nm, is presented for
      the production of open tubular monolithic porous polymer layer capillary
      (monoPLOT) columns of varying length, inner diameter (ID), and porous layer
      thickness. The developed approach allows the preparation of columns of varying
      length, because of an automated capillary delivery approach, with precisely
      controlled and uniform layer thickness and monolith morphology, from controlled
      UV power and exposure time. The relationships between direct exposure times,
      intensity, and layer thickness were determined, as were the effects of capillary
      delivery rate (indirect exposure rate), and multiple exposures on the layer
      thickness and axial distribution. Layer thickness measurements were taken by
      scanning electron microscopy (SEM), with the longitudinal homogeneity of the
      stationary phase confirmed using scanning capacitively coupled contactless
      conductivity detection (sC(4)D). The new automated UV polymerization technique
      presented in this work allows the fabrication of monoPLOT columns with a very
      high column-to-column production reproducibility, displaying a longitudinal phase
      thickness variation within +/-0.8% RSD (relative standard deviation).

PMID- 22364507
TI  - Importance of stress receptor-mediated mechanisms in the amygdala on visceral
      pain perception in an intrinsically anxious rat.
AB  - BACKGROUND: Stress worsens abdominal pain experienced by patients with irritable
      bowel syndrome (IBS), a chronic disorder of unknown origin with comorbid anxiety.
      Previously, we have demonstrated colonic hypersensitivity in Wistar-Kyoto rats
      (WKYs), a high-anxiety strain, which models abdominal pain in IBS. In low-anxiety
      rats, we have demonstrated that the central nucleus of the amygdala (CeA)
      regulates colonic hypersensitivity and anxiety induced by selective activation of
      either glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), which
      is also mediated by the corticotropin releasing factor (CRF) Type-1 receptor. The
      goal of the present study was to test the hypothesis that the CeA through GR, MR,
      and/or CRF-1R regulates colonic hypersensitivity in WKYs. METHODS: One series of
      WKYs had micropellets of a GR antagonist, an MR antagonist or cholesterol
      (control) stereotaxically implanted onto the CeA. Another series were infused in
      the CeA with CRF-1R antagonist, or vehicle. Colonic sensitivity was measured as a
      visceromotor response (VMR) to graded colorectal distension (CRD). KEY RESULTS:
      The exaggerated VMR to graded CRD in WKYs was unaffected by GR or MR antagonism
      in the CeA. In contrast, direct CeA infusion of CRF-1R antagonist significantly
      inhibited the VMR to CRD at noxious distension pressures. CONCLUSIONS &
      INFERENCES: Stress hormones in the CeA regulate colonic hypersensitivity in the
      rat through strain-dependent parallel pathways. The colonic hypersensitivity in
      WKYs is mediated by a CRF-1R mechanism in the CeA, independent of GR and MR.
      These complementary pathways suggest multiple etiologies whereby stress hormones
      in the CeA may regulate abdominal pain in IBS patients.

PMID- 22364509
TI  - Sri Lanka in global medical research: a scientific analysis of the Sri Lankan
      research output during 2000-2009.
AB  - BACKGROUND: Scientific research is an essential component in guiding improvements
      in health systems. There are no studies examining the Sri Lankan medical research
      output at international level. The present study evaluated the Sri Lankan
      research performance in medicine as reflected by the research publications output
      between years 2000-2009. METHODS: This study was based on Sri Lankan medical
      research publication data, retrieved from the SciVerse Scopus(r) from January
      2000 to December 2009. The process of article selection was as follows:
      Affiliation - 'Sri Lanka' or 'Ceylon', Publication year - 'January 2000 to
      December 2009' and Subject area - 'Life and Health Sciences'. The articles
      identified were classified according to disease, medical speciality,
      institutions, major international collaborators, authors and journals. RESULTS:
      Sri Lanka's cumulative medical publications output between years 2000-2009 was
      1,740 articles published in 160 different journals. The average annual
      publication growth rate was 9.1%. Majority of the articles were published in
      'International' (n = 950, 54.6%) journals. Most articles were descriptive studies
      (n = 611, 35.1%), letters (n-345, 19.8%) and case reports (n = 311, 17.9%). The
      articles were authored by 148 different Sri Lankan authors from 146 different
      institutions. The three most prolific local institutions were Universities of;
      Colombo (n = 547), Kelaniya (n = 246) and Peradeniya (n = 222). Eighty four
      countries were found to have published collaborative papers with Sri Lankan
      authors during the last decade. UK was the largest collaborating partner (n =
      263, 15.1%).Malaria (n = 75), Diabetes Mellitus (n = 55), Dengue (n = 53),
      Accidental injuries (n = 42) and Lymphatic filariasis (n = 40) were the major
      diseases studied. The 1,740 publications were cited 9,708 times, with an average
      citation of 5.6 per paper. The most cited paper had 203 citations, while there
      were 597 publications with no citations. The Sri Lankan authors' contribution to
      the global medical research output during the last decade was only 0.086%.
      CONCLUSION: The Sri Lankan medical research output during the last decade is only
      a small fraction of the global research output. There it is a necessity to setup
      an enabling environment for research, with a proper vision, support, funds and
      training. In addition, collaborations across the region need to be strengthened
      to face common regional health challenges.

PMID- 22364510
TI  - Occupational contact allergy to cocamidopropyl betaine and its impurities.
AB  - BACKGROUND: Contact allergy to cocamidopropyl betaine has been attributed to its
      impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. OBJECTIVES:
      To describe patients with positive patch test reactions to cocamidopropyl betaine
      related compounds in an occupational dermatology clinic. METHODS: We reviewed the
      2002-2009 patch test records at the Finnish Institute of Occupational Health for
      allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine,
      cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant
      reactions to at least one of the test substances were seen in 39% of the 1092
      patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to
      cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl
      dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to
      cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl
      dimethylamine were common. Ten of the 15 patients were diagnosed with
      occupational allergic contact dermatitis caused by cocamidopropyl betaine-related
      compounds. The sources of occupational exposure included hair care products, hair
      colours, perm wave solutions, and liquid soaps. Multiple contact allergies and
      exposure to several irritant factors were common, and all patients had hand
      eczema. CONCLUSIONS: Patch test reactions to cocamidopropyl betaine-related
      compounds are difficult to interpret, owing to extremely common irritant
      reactions. Cocamidopropyl betaine itself is probably not an allergen.
      Occupational allergic contact dermatitis caused by cocamidopropyl betaine-related
      compounds is relatively rare and, unlike non-occupational cocamidopropyl betaine
      related allergy, typically manifests as hand dermatitis.

PMID- 22364511
TI  - Reducing needle-to-balloon time by using a single guiding catheter during
      transradial primary coronary intervention.
AB  - OBJECTIVES AND BACKGROUND: It is unknown whether using a single guiding catheter
      for both nonculprit and culprit vessel angiography and intervention during
      transradial primary percutaneous coronary intervention (PCI) is feasible.
      METHODS: This single-center study enrolled 242 consecutive patients with ST
      segment elevation myocardial infarction (STEMI) who received primary PCI. Among
      them, 102 patients received primary PCI via transfemoral approach (TFI), 109
      patients received primary PCI via transradial approach using conventional
      technique (Conventional TRI), and 31 underwent primary TRI using a single guiding
      catheter (Single Guiding TRI). The catheter used for this purpose was 6 Fr RM(r)
      3.5 guiding catheter. RESULTS: Using a single guiding catheter, both coronary
      artery angiograms and intervention were successful in 30 of 31 patients (96.7%).
      Needle-to-balloon time (from puncture to first balloon) and door-to-balloon (D2B)
      time were similar between TFI and Conventional TRI groups and significantly lower
      in the Single Guiding TRI group (13.8 [TFI] and 14.1 [Conventional TRI] vs. 7.6
      minutes, P < 0.001; 89.5 [TFI] and 91.0 [Conventional TRI] vs. 68.5 minutes, P =
      0.008, respectively), whereas proportion of patients achieving D2B time within 90
      minutes increased significantly in the Single Guiding TRI group from 51.0% for
      TFI and 49.5% for Conventional TRI to 74.2% (P = 0.023). CONCLUSIONS: Primary
      transradial PCI using a single guiding catheter is feasible and highly successful
      and might allow timely restoration of blood flow in infarct-related artery.

PMID- 22364512
TI  - Oral health in nursing home residents with different cognitive statuses.
AB  - OBJECTIVE: To compare oral health in nursing home (NH) residents with different
      cognitive statuses. BACKGROUND: Oral health is a significant issue for NH
      residents because of its relationships to quality of life, systemic health and
      well-being. It is known that oral health is poor in NH residents. However, how
      oral health differs in NH residents with different cognitive statuses remains
      unclear. MATERIALS AND METHODS: Nine hundred and two NH residents were
      retrospectively recruited from a community-based geriatric dental clinic in
      Minnesota, USA. Comprehensive medical, dental, cognitive and functional
      assessments were completed for the participants. On the basis of medical history
      and cognitive status, participants were categorized into three groups: without
      cognitive impairment (non-impaired group), with cognitive impairment but no
      dementia (impaired group) and with dementia (demented group). ANOVA, Chi-square
      and Fisher's exact tests were used to compare medical, dental and functional
      statuses between groups. RESULTS: Oral hygiene was poor in NH residents. Forty
      per cent of participants in the impaired group were edentulous, significantly
      higher than the edentulism rate in the demented group (29%, p = 0.01). More than
      60% of the participants lost 16 or more teeth prior to examination. Depending on
      their cognitive status, 82-92% of the participants arrived with one or more
      caries or retained root. Dentate participants in the impaired and demented groups
      averaged about six caries or retained roots, significantly more than 4.7 caries
      or retained roots in the non-impaired group (p = 0.01). CONCLUSION: Oral health
      was poor but slightly different in NH residents with different cognitive and
      functional statuses.

PMID- 22364513
TI  - 1/3 magnetization plateau induced by magnetic field in monoclinic CoV2O6.
AB  - It was recently observed by He et al. [  J. Am. Chem. Soc.     2009  ,   131  ,  
      7554  ] that the monoclinic CoV(2)O(6) shows an unusual magnetic behavior with a
      magnetization plateau at the height of 1/3 saturated magnetization, and the
      critical magnetic field for the second jump in magnetization is about 2 times as
      large as that for the first one. By using the Wang-Landau simulation, we show
      that this stepwise magnetic behavior can be well reproduced in a distorted
      antiferromagnetic triangular model with anisotropic exchange interactions. The
      1/3 magnetization plateau here originates from the same ferrimagnetic state as
      observed in the regular triangular system, but the critical fields show different
      features due to the frustration relaxed by anisotropy. The relative value of the
      weakest interaction plays a key role in this stepwise magnetic behavior, and
      hereby the critical fields of the magnetization plateau can be accurately
      modulated by tuning exchange interactions, which provides a wide-use principle
      for the phenomena of 1/3 magnetization plateau observed in experiments.

PMID- 22364515
TI  - Transport of SiO2 nanoparticles through human skin.

PMID- 22364514
TI  - A survey of oral health in a Sudanese population.
AB  - BACKGROUND: We aimed to assess the oral health status and risk factors for dental
      caries and periodontal disease among Sudanese adults resident in Khartoum State.
      To date, this information was not available to health policy planners in Sudan.
      METHODS: A descriptive population-based survey of Sudanese adults aged >= 16
      years was conducted. After stratified sampling, 1,888 adult patients from public
      dental hospitals and dental health centres scattered across Khartoum State,
      including different ethnic groups present in Sudan, were examined in 2009-10.
      Data were collected using patient interviews and clinical examinations. Dental
      status was recorded using the DMFT index, community periodontal index (CPI), and
      a validated tooth wear index. RESULTS: Caries prevalence was high, with 87.7% of
      teeth examined having untreated decay. Periodontal disease increased in extent
      and severity with age. For 25.8% of adults, tooth wear was mild; 8.7% had
      moderate and 1% severe toothwear. Multivariate analysis revealed that decay was
      less prevalent in older age groups but more prevalent in southern tribes and
      frequent problem based attenders; western tribes and people with dry mouths who
      presented with less than18 sound, untreated natural teeth (SUNT). Older age
      groups were more likely to present with tooth wear; increasing age and gender
      were associated with having periodontal pocketing >= 4 mm. CONCLUSIONS: The
      prevalence of untreated caries and periodontal disease was high in this
      population. There appear to be some barriers to restorative dental care, with
      frequent use of dental extractions to treat caries and limited use of restorative
      dentistry. Implementation of population-based strategies tailored to the
      circumstances of Sudanese population is important to improve oral health status
      in Sudan.

PMID- 22364516
TI  - Evolutionary factor analysis of replicated time series.
AB  - In this article, we develop a novel method that explains the dynamic structure of
      multi-channel electroencephalograms (EEGs) recorded from several trials in a
      motor-visual task experiment. Preliminary analyses of our data suggest two
      statistical challenges. First, the variance at each channel and cross-covariance
      between each pair of channels evolve over time. Moreover, the cross-covariance
      profiles display a common structure across all pairs, and these features
      consistently appear across all trials. In the light of these features, we develop
      a novel evolutionary factor model (EFM) for multi-channel EEG data that
      systematically integrates information across replicated trials and allows for
      smoothly time-varying factor loadings. The individual EEGs series share common
      features across trials, thus, suggesting the need to pool information across
      trials, which motivates the use of the EFM for replicated time series. We explain
      the common co-movements of EEG signals through the existence of a small number of
      common factors. These latent factors are primarily responsible for processing the
      visual-motor task which, through the loadings, drive the behavior of the signals
      observed at different channels. The estimation of the time-varying loadings is
      based on the spectral decomposition of the estimated time-varying covariance
      matrix.

PMID- 22364517
TI  - The clinical spectrum of the m.10191T>C mutation in complex I-deficient Leigh
      syndrome.
AB  - Mitochondrial respiratory chain diseases represent one of the most common
      inherited neurometabolic disorders of childhood, affecting a minimum of 1 in 7500
      live births. The marked clinical, biochemical, and genetic heterogeneity means
      that accurate genetic counselling relies heavily upon the identification of the
      underlying causative mutation in the individual and determination of carrier
      status in the parents. Isolated complex I deficiency is the most common
      respiratory chain defect observed in children, resulting in organ-specific or
      multisystem disease, but most often presenting as Leigh syndrome, for which
      mitochondrial DNA mutations are important causes. Several recurrent, pathogenic
      point mutations in the MTND3 gene - including m.10191T>C (p.Ser45Pro) - have been
      previously identified. In this short clinical review we evaluate the case reports
      of the m.10191T>C mutation causing complex I-deficient Leigh syndrome described
      in the literature, in addition to two new ones diagnosed in our laboratory. Both
      of these appear to have arisen de novo without transmission of the mutation from
      mother to offspring, illustrating the importance not only of fully characterizing
      the mitochondrial genome as part of the investigation of children with complex I
      deficient Leigh syndrome but also of assessing maternal samples to provide
      crucial genetic advice for families.

PMID- 22364519
TI  - Acute oliguric renal failure in HELLP syndrome: case report and review of
      literature.
AB  - We describe a 32-year-old female with past medical history of preeclampsia, who
      presented at 29th week of gestation of her second pregnancy with abdominal pain,
      emesis, and diarrhea. Initial evaluation revealed hypertension, placental
      abruption, and intrauterine fetal death. After spontaneous rupture of membranes,
      a stillborn fetus was delivered. The clinical course was complicated by seizures
      and acute kidney injury requiring hemodialysis. She also exhibited
      microangiopathic hemolytic anemia, thrombocytopenia, and elevated liver enzymes
      (consistent with HELLP syndrome). A biopsy showed acute renal cortical necrosis.

PMID- 22364520
TI  - Aging-associated alteration of telomere length and subtelomeric status in female
      patients with Parkinson's disease.
AB  - A telomere is a repetitive DNA structure at chromosomal ends that stabilizes the
      chromosome structure and prevents harmful end-to-end recombinations. The telomere
      length of somatic cells becomes shorter with aging because of the "end
      replication problem." This telomere shortening is accelerated by
      pathophysiological conditions including daily mental stress. Living with
      Parkinson's disease (PD) causes physical and mental stress; therefore, the
      authors hypothesized that the telomere length of somatic cells was shortened
      excessively in patients with PD. In order to detect PD-associated somatic
      telomeric alterations, the telomere length and subtelomeric methylation status of
      peripheral leukocytes of PD patients were assessed by Southern blotting, using
      methylation-sensitive and -insensitive isoschizomers. The results demonstrated
      that the peripheral leukocytes of Japanese female patients with PD bore fewer
      long telomeres and a proportional increase of hypomethylated subtelomeres in
      short telomeres in comparison with the healthy controls. This study indicates
      that with the neurodegeneration associated with PD, telomeric and subtelomeric
      structural alterations occur. These structural telomere alterations most likely
      occur secondary to the acceleration of aging-associated telomeric changes and the
      accelerated loss of cells bearing short telomeres.

PMID- 22364521
TI  - Development of a novel antifouling platform for biosensing probe immobilization
      from methacryloyloxyethyl phosphorylcholine-containing copolymer brushes.
AB  - The immobilization of thiol-terminated poly[(methacrylic acid)-ran-(2
      methacryloyloxyethyl phosphorylcholine)] (PMAMPC-SH) brushes on gold-coated
      surface plasmon resonance (SPR) chips was performed using the "grafting to"
      approach via self-assembly formation. The copolymer brushes provide both
      functionalizability and antifouling characteristics, desirable features
      mandatorily required for the development of an effective platform for probe
      immobilization in biosensing applications. The carboxyl groups from the
      methacrylic acid (MA) units were employed for attaching active biomolecules that
      can act as sensing probes for biospecific detection of target molecules, whereas
      the 2-methacryloyloxyethyl phosphorylcholine (MPC) units were introduced to
      suppress unwanted nonspecific adsorption. The detection efficiency of the biotin
      immobilized PMAMPC brushes with the target molecule, avidin (AVD), was evaluated
      in blood plasma in comparison with the conventional 2D monolayer of 11
      mercaptoundecanoic acid (MUA) and homopolymer brushes of poly(methacrylic acid)
      (PMA) also immobilized with biotin using the SPR technique. Copolymer brushes
      with 79 mol % MPC composition and a molecular weight of 49.3 kDa yielded the
      platform for probe immobilization with the best performance considering its high
      S/N ratio as compared with platforms based on MUA and PMA brushes. In addition,
      the detection limit for detecting AVD in blood plasma solution was found to be
      1.5 nM (equivalent to 100 ng/mL). The results have demonstrated the potential for
      using these newly developed surface-attached PMAMPC brushes for probe
      immobilization and subsequent detection of designated target molecules in complex
      matrices such as blood plasma and clinical samples.

PMID- 22364522
TI  - The regenerative potential of angiotensin AT2 receptor in cardiac repair.
AB  - Angiotensin II, the main effector peptide of the renin-angiotensin system,
      interferes with cardiac remodeling and repair through its receptors, including
      AT(1) and AT(2) receptor (R). The functional relevance of the previously
      neglected AT(2)R is currently intensively studied. Pharmacological therapies with
      AT(1)R blockers have improved outcomes in patients with ischemic heart injury,
      probably involving an indirect stimulation of AT(2)R. Previous experimental
      studies have clearly shown a protective action of AT(2)R in tissue repair and
      regeneration. We have recently identified the c-kit(+)AT(2)R(+) progenitor cell
      population in rat heart and bone marrow, which increases after induction of
      myocardial infarction. Further experimental evidence demonstrates that AT(2)R
      mediates cardiac homing and repair process of the c-kit(+) progenitor cells.
      AT(2)R stimulation through AT(1)R blockers or directly by AT(2)R agonist or both
      in combination may potentially offer the translational options to improve the
      regenerative potentials of stem/progenitor cells derived from patients with
      cardiovascular disease.

PMID- 22364523
TI  - 'Doing things together': male caregivers' experiences of giving care to patients
      in forensic psychiatric care.
AB  - Studies into work carried out by male caregivers in a care environment in which
      male patients and male caregivers constitute a majority are lacking. The purpose
      of this study was to illuminate the experiences of male caregivers in providing
      care for patients in forensic psychiatric care. The study has a qualitative
      design and data were constituted by interviews with six male caregivers at a
      clinic of forensic psychiatry in a town in central Sweden. The method of analysis
      chosen was latent content analysis. The results consist of four themes:
      Activities as a component of care, Social training as the basis of care, Feelings
      of powerlessness and Seeing the complete person. The experience that comes out
      most distinctly in the descriptions given by caregivers involves performing
      activities together with the patients. The activities had different significances
      and these contribute to creating a more secure care relationship, in which the
      boundaries between personnel and patients become less clear. Physical activities
      contribute to recreating the patient's health. Social training appears as a
      component of the care in which the significance of rules and routines in the
      operations was integrated. Feelings of powerlessness arise when the caregivers do
      not experience that the care given on the ward contributes to recreating health
      for the patients. Seeing the complete person behind the crime constitutes the
      themes that can be said to summarize the meaning of the work carried out by male
      caregivers.

PMID- 22364524
TI  - Epigenetics: a paradigm shift in understanding Alzheimer's disease.

PMID- 22364526
TI  - Two cycles of the PS-341/bortezomib, adriamycin, and dexamethasone combination
      followed by autologous hematopoietic cell transplantation in newly diagnosed
      multiple myeloma patients.
AB  - INTRODUCTION: Treatment with 3-6 cycles of PS-341/bortezomib, adriamycin, and
      dexamethasone (PAD) has been explored in terms of induction therapy prior to
      autologous stem cell transplantation (ASCT) in patients with multiple myeloma
      (MM). We evaluated the effects of two cycles of PAD given before ASCT. PATIENTS
      AND METHODS: Patients received two 21-d cycles of PAD (bortezomib 1.3 mg/m(2) * 4
      d, adriamycin 9 mg/m(2) * 4 d, and dexamethasone 40 mg * 4 d * 2). Starting on
      day 12 of cycle 2, patients were given subcutaneous granulocyte-colony
      stimulating factor to mobilize peripheral blood stem cells (PBSCs). Following
      PBSC harvesting, ASCT was performed using high-dose melphalan, followed by
      thalidomide. RESULTS: A total of 32 patients were enrolled. Of 31 who completed
      two cycles of PAD, 25 (81%) achieved a partial response (PR) or better. Major
      adverse events were cytopenia, with grade I/II neurotoxicity evident during 4.8%
      of PAD cycles. Two patients were withdrawn from the study prior to PBSC
      collection. Thirty patients showed successful mobilization of PBSCs and underwent
      ASCT, with all 30 showing adequate neutrophil and platelet recovery. Following
      ASCT, 14 patients (47%) achieved a complete response (CR), 8 (27%) a very good
      partial response (VGPR), and 6 (20%) PR. Thalidomide was given to 25 patients
      after ASCT, as maintenance therapy. Twelve patients showed better responses after
      administration of thalidomide, and a total of 21 patients (70%) achieved CR. The
      5-yr probabilities of overall and progression-free survival were 71.1% and 23.5%,
      respectively. CONCLUSION: A short course of PAD was effective as an induction
      treatment before ASCT in patients newly diagnosed with MM. Prospective
      comparisons with longer courses of such treatment are needed.

PMID- 22364527
TI  - Validation of the Swedish version of the chronic liver disease questionnaire.

PMID- 22364525
TI  - Early and individualized goal-directed therapy for trauma-induced coagulopathy.
AB  - Severe trauma-related bleeding is associated with high mortality. Standard
      coagulation tests provide limited information on the underlying coagulation
      disorder. Whole-blood viscoelastic tests such as rotational thromboelastometry or
      thrombelastography offer a more comprehensive insight into the coagulation
      process in trauma. The results are available within minutes and they provide
      information about the initiation of coagulation, the speed of clot formation, and
      the quality and stability of the clot. Viscoelastic tests have the potential to
      guide coagulation therapy according to the actual needs of each patient, reducing
      the risks of over- or under-transfusion. The concept of early, individualized and
      goal-directed therapy is explored in this review and the AUVA Trauma Hospital
      algorithm for managing trauma-induced coagulopathy is presented.

PMID- 22364528
TI  - 1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia
      inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia.
AB  - The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a
      structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of
      enzymes for the treatment of anemia is described. The initial hit class,
      spirooxindoles, was identified through affinity selection mass spectrometry (AS
      MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting
      PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were
      optimized as an advanced lead class derived from the original spiroindole hit. A
      new set of general conditions for C-N coupling, developed using a high-throughput
      experimentation (HTE) technique, enabled a full SAR analysis of the
      spirohydantoins. This rapid and directed SAR exploration has resulted in the
      first reported examples of hydantoin derivatives with good PK in preclinical
      species. Potassium channel off-target activity (hERG) was successfully eliminated
      through the systematic introduction of acidic functionality to the molecular
      structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes
      was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins
      represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a
      robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species.
      This profile deems spirohydantoins as attractive short-acting PHDi inhibitors
      with the potential for treatment of anemia.

PMID- 22364529
TI  - Impact of electronic medical record on physician practice in office settings: a
      systematic review.
AB  - BACKGROUND: Increased investments are being made for electronic medical records
      (EMRs) in Canada. There is a need to learn from earlier EMR studies on their
      impact on physician practice in office settings. To address this need, we
      conducted a systematic review to examine the impact of EMRs in the physician
      office, factors that influenced their success, and the lessons learned. RESULTS:
      For this review we included publications cited in Medline and CINAHL between 2000
      and 2009 on physician office EMRs. Studies were included if they evaluated the
      impact of EMR on physician practice in office settings. The Clinical Adoption
      Framework provided a conceptual scheme to make sense of the findings and allow
      for future comparison/alignment to other Canadian eHealth initiatives.In the
      final selection, we included 27 controlled and 16 descriptive studies. We
      examined six areas: prescribing support, disease management, clinical
      documentation, work practice, preventive care, and patient-physician interaction.
      Overall, 22/43 studies (51.2%) and 50/109 individual measures (45.9%) showed
      positive impacts, 18.6% studies and 18.3% measures had negative impacts, while
      the remaining had no effect. Forty-eight distinct factors were identified that
      influenced EMR success. Several lessons learned were repeated across studies: (a)
      having robust EMR features that support clinical use; (b) redesigning EMR
      supported work practices for optimal fit; (c) demonstrating value for money; (d)
      having realistic expectations on implementation; and (e) engaging patients in the
      process. CONCLUSIONS: Currently there is limited positive EMR impact in the
      physician office. To improve EMR success one needs to draw on the lessons from
      previous studies such as those in this review.

PMID- 22364532
TI  - AAC and ICF: A good fit to emphasize outcomes.

PMID- 22364530
TI  - Comparison between amine fluoride and chlorhexidine with institutionalized
      elders: a pilot study.
AB  - OBJECTIVE: Compare the efficacy of amine fluoride toothpaste and gel with
      chlorhexidine spray in an institutionalised population. BACKGROUND: People who
      live in nursing homes have poorer oral hygiene because of their dependency for
      the basic activities of daily living as they rely on caregivers. METHODS: Twenty
      six people over 65 years old who had at least four teeth and living in a nursing
      home. They were assigned to three groups: A: amine fluoride toothpaste and once a
      week amine fluoride gel (Elmex((r)) ), B: 0.12% spray-chlorhexidine once a day
      (Perio-Aid((r)) ) and C: brush teeth without toothpaste. The plaque and gingival
      index of Silness and Loe, General Oral Health Assessment Index, McLeran and
      Pfeiffer index were recorded, and the number of colonies of Streptoccocus mutans
      and Lactobacillus and the remineralisation of caries were evaluated using
      Diagnodent((r)). Measurements were taken at the beginning of the study and after
      6 months. RESULTS:   Twenty-two people finished the study. No group showed a
      statistical difference in the plaque or gingival index, but there was a tendency
      to show improvement in the amine fluoride group. There was also no difference
      between the number of colonies of either S. mutans or lactobacillus. There was a
      significant difference between the plaque and gingival index and the cognitive
      status (p=0.0054), along with their requirement for assistance to perform good
      oral hygiene (p=0.0001). Both products remineralised the carious lesions in this
      period compared with the control group (p=0.0151). CONCLUSION: The plaque and
      gingival indices did not improve during the study, but both products
      remineralised the previous caries lesions.

PMID- 22364533
TI  - Communication, disability, and the ICF-CY.
AB  - The child's interactions with persons in the proximal environment constitute the
      context for development of communication. Within early close relationships, the
      child acquires communication skills; developmental outcomes are defined by the
      continuous dynamic interactions of the child, the experiences provided by the
      family and close environment, and the use of different means of augmentative and
      alternative communication (AAC). Communication problems manifest in a variety of
      ways and at different levels of severity. The nature of problems differs as a
      function of the child's age and diagnosed condition, the communication skills of
      interaction partners, and the availability of communication aids. The focus for
      assessment and intervention may be the child, the family, the close environment
      and/or the interactions between them. Clarifying these varied functions and
      environmental factors is crucial for appropriate assessment and provision of
      augmentative and alternative communication (AAC) interventions. This paper
      reviews issues in assessment and intervention for children in need of AAC and
      presents the World Health Organizations' (WHO) International Classification of
      Functioning, Disability and Health version for Children and Youth (ICF-CY) as a
      tool to enhance assessment and intervention in the AAC field.

PMID- 22364534
TI  - Implementation of the International Classification of Functioning, Disability and
      Health (ICF) and the ICF Children and Youth Version (ICF-CY) within the context
      of augmentative and alternative communication.
AB  - The purpose of this article is to discuss the implementation of the International
      Classification of Functioning, Disability and Health (ICF), and the ICF version
      for Children and Youth (ICF-CY), within the context of augmentative and
      alternative communication (AAC). First, the use of the ICF and the ICF-CY in AAC
      research is analyzed. Second, examples of training and implementation of ICF from
      other contexts besides AAC are provided. Finally, we synthesize data to provide
      directions for future implementation of the ICF and ICF-CY in the field of AAC.
      We conclude that, within AAC, organizational routines and intervention documents
      need to be adapted to the universal language and classification framework of the
      ICF and ICF-CY. Furthermore, examples are needed to demonstrate how factors
      affect implementation at organizational and individual levels.

PMID- 22364535
TI  - Developing the ICF-CY for AAC profile and code set for children who rely on AAC.
AB  - We describe the ICF-CY for AAC Profile, a tool to integrate information about the
      multiple factors affecting communication skill development and use in school-aged
      children with complex communication needs. The Profile uses the World Health
      Organization's International Classification of Functioning, Disability and Health
      - Children & Youth Version ( WHO, 2007 ) as its framework. We propose that the
      ICF-CY for AAC Profile constitutes a code set for AAC users and discuss the
      iterative process of code-set development. The Profile is one component of a
      proposed process to guide the development of educational goals for children in
      Grades kindergarten-12 who currently or potentially rely on AAC.

PMID- 22364536
TI  - School participation and social networks of children with complex communication
      needs, physical disabilities, and typically developing peers.
AB  - The aim of the study was to describe and compare the school participation and
      social networks of children with physical disabilities and complex communication
      needs (Group CCN), children with physical disabilities only (Group PD), and
      children with typical development (Group TD). The 39 participants, 10-15 years of
      age, were observed for 4 hours at school. School staff and the parent and/or
      child provided information on children's social networks. A striking observation
      was that, while participants in Group TD continuously conversed and socialized
      with peers inside and outside classrooms; those in Group CCN rarely used aided
      AAC, were provided with limited communication opportunities at school, and had
      fewer acquaintances and friends. Findings warrant intervention at the
      participation level at school and in the community.

PMID- 22364537
TI  - An examination of relations between participation, communication and age in
      children with complex communication needs.
AB  - The aim of this study was to examine variation in the frequency of children's
      participation in out-of-school activities as a function of speech
      intelligibility, perceived effectiveness of the child's communication aid, and
      age. Sixty-nine caregivers of children with complex communication needs provided
      with communication aids completed a questionnaire survey. Rate of participation
      was higher for younger than for older children, particularly in recreational
      activities. Younger children with partial intelligibility participated more
      frequently in recreational and social activities than both younger children
      without speech and older children. Results and limitations are discussed within
      the context of participation research in childhood disability, highlighting the
      impact of communicative resources and maturation on everyday participation.

PMID- 22364538
TI  - Using the WHO-ICF with talking mats to enable adults with long-term communication
      difficulties to participate in goal setting.
AB  - The World Health Organization International Classification of Functioning,
      Disability and Health (WHO-ICF) provides a framework that helps rehabilitation
      staff to take a holistic view of the patient. However, it is used predominantly
      by professionals rather than by active participation on behalf of the person with
      the disability. In addition, the language used within the framework can be
      difficult for patients to understand. In order to address these issues the
      Activities and Participation section of the ICF has been adapted by using graphic
      symbols. It has been used in conjunction with Talking Mats(TM 1 ), a low-tech
      communication framework, to help adults with long-term conditions participate in
      goal setting. This paper describes how this was done and provides examples from
      clinical practice. The paper discusses how this combined framework can empower
      people with communication difficulties and long-term conditions to become active
      participants in the rehabilitation process by identifying their own goals,
      indicating changing priorities and tracking their progress.

PMID- 22364540
TI  - A network-based analysis of the 1861 Hagelloch measles data.
AB  - In this article, we demonstrate a statistical method for fitting the parameters
      of a sophisticated network and epidemic model to disease data. The pattern of
      contacts between hosts is described by a class of dyadic independence exponential
      family random graph models (ERGMs), whereas the transmission process that runs
      over the network is modeled as a stochastic susceptible-exposed-infectious
      removed (SEIR) epidemic. We fit these models to very detailed data from the 1861
      measles outbreak in Hagelloch, Germany. The network models include parameters for
      all recorded host covariates including age, sex, household, and classroom
      membership and household location whereas the SEIR epidemic model has
      exponentially distributed transmission times with gamma-distributed latent and
      infective periods. This approach allows us to make meaningful statements about
      the structure of the population-separate from the transmission process-as well as
      to provide estimates of various biological quantities of interest, such as the
      effective reproductive number, R. Using reversible jump Markov chain Monte Carlo,
      we produce samples from the joint posterior distribution of all the parameters of
      this model-the network, transmission tree, network parameters, and SEIR
      parameters-and perform Bayesian model selection to find the best-fitting network
      model. We compare our results with those of previous analyses and show that the
      ERGM network model better fits the data than a Bernoulli network model previously
      used. We also provide a software package, written in R, that performs this type
      of analysis.

PMID- 22364541
TI  - Synthesis of Au-based porous magnetic spheres by selective laser heating in
      liquid.
AB  - We report the synthesis of Au-based submicrometer-sized spherical particles with
      uniform morphology/size and integrated porosity-magnetic property in a single
      particles. The particles are synthesized by a two-step process: (a) selective
      pulsed laser heating of colloidal nanoparticles to form particles with Au-rich
      core and Fe-rich shell and (b) acid treatment which leads to formation of porous
      architecture on particle surface. The simple, fast, inexpensive technique that is
      proposed demonstrates very promising perspectives for synthesis of composite
      particles.

PMID- 22364543
TI  - Modulation of GABAergic synaptic currents and current responses by alpha-thujone
      and dihydroumbellulone.
AB  - alpha-Thujone (1a), a constituent of wormwood, has been suspected to cause
      adverse psychoactive reactions in addicted drinkers of absinthe. While the
      content of 1a in absinthe is too low for such effects, at higher doses it can
      indeed induce seizures and inhibit GABA(A) receptors (GABA(A)Rs). The effect of
      1a on GABAergic synaptic currents and the mechanisms by which it modulates
      GABA(A)Rs remain unknown. To address these issues, cultured hippocampal neurons
      were used to investigate the action of 1a on GABAergic miniature inhibitory
      postsynaptic currents (mIPSCs) and on responses to exogenous GABA applications.
      Since lipophilic compounds often show nonspecific actions related to their
      hydrophobicity, the action of 1a was compared to that of dihydroumbellulone (2),
      a configurationally pseudoenantiomeric constitutional isomer. alpha-Thujone (1a)
      reduced mIPSC frequency and amplitude and also moderately affected their
      kinetics, indicating both pre- and postsynaptic mechanisms. Analysis of current
      responses to exogenous GABA revealed that 1a reduced their amplitude, affecting
      their onset, desensitization, and deactivation, suggesting an effect on receptor
      gating. In contrast, 2 caused only a weak or negligible effect on GABAergic
      currents, supporting the effects of 1a on GABAergic inhibition as being due to
      specific interactions with GABA(A)Rs.

PMID- 22364544
TI  - Advances and applications of induced pluripotent stem cells.
AB  - Direct reprogramming of somatic cells into pluripotent cells is an emerging
      technology for creating patient-specific cells, and potentially opens new
      scenarios in medical and pharmacological fields. From the discovery of Shinya
      Yamanaka, who first obtained pluripotent cells from fibroblasts by retrovirus
      derived ectopic expression of defined embryonic transcription factors, new
      methods have been developed to generate safe induced pluripotent stem (iPS) cells
      without genomic manipulations. This review will focus on the recent advances in
      iPS technology and their application in pharmacology and medicine.

PMID- 22364546
TI  - Dispersion serial dilution methods using the gradient diluter device.
AB  - A solute aspirated into a prefilled tube of diluent undergoes a dilution effect
      known as dispersion. Traditionally the effects of dispersion have been considered
      a negative consequence of using liquid-filled fixed-tip liquid handlers. We
      present a novel device and technique that utilizes the effects of dispersion to
      the benefit of making dilutions. The device known as the Gradient Diluter extends
      the dilution range of practical serial dilutions to six orders of magnitude in
      final volumes as low as 10 MUL. Presented are the device, dispersion methods, and
      validation tests using fluorescence detection of sulforhodamine and the high
      performance liquid chromatography/ultraviolet detection of furosemide. In
      addition, a T-cell inhibition assay of a relevant downstream protein is used to
      demonstrate IC(50) curves made with the Gradient Diluter compare favorably with
      those generated by hand.

PMID- 22364547
TI  - Recurrent seizures in tramadol intoxication: implications for therapy based on
      100 patients.
AB  - Tramadol is an atypical opioid analgesic used in the treatment of mild to
      moderate pain. Despite being a GABA(A) agonist, seizures are a prominent
      complication with its therapeutic use, abuse or overdose. For patients who have
      had a tramadol-induced seizure, the likelihood of recurrent seizures and the need
      for emergent anticonvulsant prophylaxis is unknown. However, treatment of
      patients with anticonvulsants prophylactically may cause adverse effects and
      increased morbidity in tramadol poisoning. We studied the outcome and frequency
      of recurrent seizures in tramadol-intoxicated patients in an attempt to determine
      the need for prophylactic anticonvulsant therapy. This was a retrospective cohort
      study of tramadol-intoxicated patients who had at least one seizure. Patients'
      age, sex, cause(s) of intoxication, route of poisoning, dose or number of
      capsules or tablets taken, vital signs, other signs or symptoms, numbers of
      seizures, length of stay, co-ingestions and past medical history were
      ascertained. Exactly 100 patients met the inclusion criteria. Eighty-two per cent
      were men, and 50% were between 21 and 30 years old. By our standard clinical
      protocol, none were treated with seizure prophylaxis after their first seizure.
      Only 7% had recurrent seizures and all patients recovered without sequelae.
      Because of the low risk of multiple seizures in tramadol poisoning and the lack
      of morbidity in patients who do seize, it appears to be unnecessary to administer
      prophylactic anticonvulsant therapy in patients with tramadol poisoning, even if
      they have an initial seizure.

PMID- 22364545
TI  - Bioluminescence methodology for the detection of protein-protein interactions
      within the voltage-gated sodium channel macromolecular complex.
AB  - Protein-protein interactions are critical molecular determinants of ion channel
      function and emerging targets for pharmacological interventions. Yet, current
      methodologies for the rapid detection of ion channel macromolecular complexes are
      still lacking. In this study we have adapted a split-luciferase complementation
      assay (LCA) for detecting the assembly of the voltage-gated Na+ (Nav) channel C
      tail and the intracellular fibroblast growth factor 14 (FGF14), a functionally
      relevant component of the Nav channelosome that controls gating and targeting of
      Nav channels through direct interaction with the channel C-tail. In the LCA, two
      complementary N-terminus and C-terminus fragments of the firefly luciferase were
      fused, respectively, to a chimera of the CD4 transmembrane segment and the C-tail
      of Nav1.6 channel (CD4-Nav1.6-NLuc) or FGF14 (CLuc-FGF14). Co-expression of CLuc
      FGF14 and CD4-Nav1.6-NLuc in live cells led to a robust assembly of the
      FGF14:Nav1.6 C-tail complex, which was attenuated by introducing single-point
      mutations at the predicted FGF14:Nav channel interface. To evaluate the dynamic
      regulation of the FGF14:Nav1.6 C-tail complex by signaling pathways, we
      investigated the effect of kinase inhibitors on the complex formation. Through a
      platform of counter screenings, we show that the p38/MAPK inhibitor, PD169316,
      and the IkappaB kinase inhibitor, BAY 11-7082, reduce the FGF14:Nav1.6 C-tail
      complementation, highlighting a potential role of the p38MAPK and the
      IkappaB/NFkappaB pathways in controlling neuronal excitability through protein
      protein interactions. We envision the methodology presented here as a new
      valuable tool to allow functional evaluations of protein-channel complexes toward
      probe development and drug discovery targeting ion channels implicated in human
      disorders.

PMID- 22364548
TI  - The prevalence of type 2 idiopathic macular telangiectasia in two African
      populations.
AB  - PURPOSE: Type 2 idiopathic macular telangiectasia (MacTel) is a progressive
      retinal disease associated with a slow deterioration of visual acuity, starting
      in the fifth to seventh decades of life. The etiology and pathogenesis of the
      disease are little known, and no effective therapy is available. We aimed to
      estimate the prevalence and describe the phenotype of type 2 MacTel in two
      African populations. METHODS: From two population-based cross-sectional surveys
      conducted nationally in Nigeria and in the Nakuru district of Kenya, patients
      with fundus features of type 2 MacTel were selected. Diagnosis was based on color
      fundus images, grading performed according to the MacTel Study protocol and
      staged using the Gass and Blodi system. Disease phenotype and clinical
      characteristics of affected participants were assessed. RESULTS: Of 8599 total
      participants, five showed a phenotype compatible with type 2 MacTel. Prevalence
      was estimated as 0.06% (95% confidence interval [CI] 0.02-0.21%) in Kenya, 0.06%
      (95% CI 0.01-0.17%) in Nigeria, and overall at 0.06% (95% CI 0.02-0.14%). Mean
      age was 62 years (SD 5 years), four of five affected participants were female,
      and none had a history of diabetes. Median corrected visual acuity was 6/12 in
      the better eye and 6/69 in the worse eye. CONCLUSIONS: The estimated prevalence
      and phenotype of type 2 MacTel in the African populations examined were similar
      to those in predominantly white populations. All data published so far are based
      on the analysis of color fundus images only and are thus likely to underestimate
      the true prevalence of this disease.

PMID- 22364549
TI  - Digested Ara h 1 loses sensitizing capacity when separated into fractions.
AB  - The major peanut allergen Ara h 1 is an easily digestible protein under
      physiological conditions. The present study revealed that pepsin digestion
      products of Ara h 1 retained the sensitizing potential in a Brown Norway rat
      model, while this sensitizing capacity was lost by separating the digest into
      fractions by gel permeation chromatography. Protein chemical analysis showed that
      the peptide composition as well as the aggregation profiles of the fractions of
      Ara h 1 digest differed from that of the whole pool. These results indicate that
      the sensitizing capacity of digested Ara h 1 is a consequence of the peptides
      being in an aggregated state resembling the intact molecule or that most peptides
      of the digests need to be present in the same solution, having a synergistic or
      adjuvant effect and thereby augmenting the immune response against other
      peptides.

PMID- 22364550
TI  - High content screening for compounds that induce early stages of human embryonic
      stem cell differentiation.
AB  - Embryonic stem cells, due to their self-renewal and pluripotency properties, can
      be used to repair damaged tissues and as an unlimited source of differentiated
      cells. Although stem cells represent an important opportunity for cell based
      therapy and small molecules screening (in the context of drug or target
      discovery) many drawbacks are still preventing their widespread use. One of the
      most significant limitations is related to the complexity, as well as the
      reliability, of current protocols driving stem cells into any homogeneously
      differentiated cellular population. In this respect there is a strong demand for
      molecular agents promoting differentiation and thereby enabling robust, efficient
      and safe production of differentiated cells. In order to identify novel molecules
      that enhance early stages of differentiation, we developed an image based high
      content screening (HCS) approach using human embryonic stem cells (hESC). In our
      approach, we took advantage of custom image mining software specifically adapted
      for the selection of stem cell differentiation agents and the rejection of false
      positive hits. As a proof of concept -3500 small molecules originating from
      commercial libraries were screened and a number of molecules of interests were
      identified. These molecules show stem cell differentiation properties comparable
      to the phenotypic signature obtained with the reference compound retinoic acid.

PMID- 22364551
TI  - Pentafluorophenylammonium triflate as a mild and new organocatalyst for acylation
      of alcohols, phenols, and amines under solvent-free condition.
AB  - A simple, inexpensive, environmentally friendly and efficient route for the
      acylation of a number of alcohols, phenols and amines using
      pentafluorophenylammonium triflate (PFPAT) as a catalyst is described. PFPAT
      organocatalyst is air-stable, cost-effective, easy to handle, and easily removed
      from the reaction mixtures.

PMID- 22364552
TI  - Effect of classroom air quality on students' concentration: results of a cluster
      randomized cross-over experimental study.
AB  - To assess the effect of indoor air quality as indicated by the median carbon
      dioxide (CO2) level in the classroom on the concentration performance (CP) of
      students, a cross-over cluster-randomized experimental study was conducted in 20
      classrooms with mechanical ventilation systems. Test conditions 'worse' (median
      CO2 level on average 2115 ppm) and 'better' (median CO2 level on average 1045
      ppm) were established by the regulation of the mechanical ventilation system on
      two days in one week each in every classroom. Concentration performance was
      quantified in students of grade three and four by the use of the d2-test and its
      primary parameter 'CP' and secondary parameters 'total number of characters
      processed' (TN) and 'total number of errors' (TE). 2366 d2-tests from 417
      students could be used in analysis. In hierarchical linear regression accounting
      for repeated measurements, no significant effect of the experimental condition on
      CP or TN could be observed. However, TE was increased significantly by 1.65 (95%
      confidence interval 0.42-2.87) in 'worse' compared to 'better' condition. Thus,
      low air quality in classrooms as indicated by increased CO2 levels does not
      reduce overall short-term CP in students, but appears to increase the error rate.
      PRACTICAL IMPLICATIONS: This study could not confirm that low air quality in
      classrooms as indicated by increased CO2 levels reduces short-term concentration
      performance (CP) in students; however, it appears to affect processing accuracy
      negatively. To ensure a high level of accuracy, good air quality characterized,
      for example, by low CO2 concentration should be maintained in classrooms.

PMID- 22364553
TI  - Inhibitory effect of prolactin on Toxoplasma proliferation in peripheral blood
      mononuclear cells from patients with hyperprolactinemia.
AB  - Despite many years of studies on the mechanisms of immunological defence
      responses induced in host organisms by Toxoplasma, no satisfactory
      immunoprophylaxis or chemotherapy have yet been established for humans. Thus,
      alternative methods to prevent toxoplasmosis and to enhance the efficacy of
      currently used antitoxoplasmic drugs are under evaluation. In this work, we
      strove to determine the influence of human prolactin (endogenous present in serum
      -sPRL and recombinant--rhPRL) on the course of Toxoplasma infection of peripheral
      blood mononuclear cells (PBMC) originating from female hyperprolactinemia
      patients. This study revealed that exogenous rhPRL as well as autologous sPRL
      from inactivated sera significantly restricted intracellular growth of Toxoplasma
      in PBMC cultures. Moreover, analysis of IL-10 production by PBMC infected with
      Toxoplasma and cultured in the presence of sPRL showed a positive correlation
      between sPRL concentration and the level of IL-10. The obtained results could
      indicate the possible protective action of PRL in a host organism infected with
      Toxoplasma and suggest that a significant increase in the serum PRL level, during
      pregnancy for instance, might significantly limit the risk of Toxoplasma
      spreading and could play an important role in natural protection against
      toxoplasmosis. The mechanism of inhibitory effect of PRL needs further detailed
      study.

PMID- 22364554
TI  - Paediatric CT scan usage and referrals of children to computed tomography in
      Germany--a cross-sectional survey of medical practice and awareness of radiation
      related health risks among physicians.
AB  - BACKGROUND: Computed tomography (CT) is a major source of ionizing radiation
      exposure in medical diagnostic. Compared to adults, children are supposed to be
      more susceptible to health risks related to radiation. The purpose of a cross
      sectional survey among office-based physicians in Germany was the assessment of
      medical practice in paediatric CT referrals and to investigate physicians'
      knowledge of radiation doses and potential health risks of radiation exposure
      from CT in children. METHODS: A standardized questionnaire was distributed to all
      paediatricians and surgeons in two defined study areas. Furthermore, the study
      population included a random sample of general practitioners in the two areas.
      The questionnaire covered the frequency of referrals for paediatric CT
      examinations, the medical diagnoses leading to paediatric CT referrals,
      physicians' knowledge of radiation doses and potential health risks of radiation
      exposure from CT in children. RESULTS: A total of 295 (36.4%) physicians
      responded. 59% of the doctors had not referred a child to CT in the past year,
      and approximately 30% referred only 1-5 children annually. The most frequent
      indications for a CT examination in children were trauma or a suspected cancer.
      42% of the referrals were related to minor diagnoses or unspecific symptoms. The
      participants underestimated the radiation exposure due to CT and they
      overestimated the radiation exposure due to conventional X-ray examinations.
      CONCLUSIONS: In Germany, the frequency of referrals of children to computed
      tomography is moderate. The knowledge on the risks from radiation exposure among
      office-based physicians in our sample varied, but there was a tendency to
      underestimate potential CT risks. Advanced radiological training might lead to
      considerable amendments in terms of knowledge and practice of CT referral.

PMID- 22364555
TI  - Reliability and accuracy of anthropometry performed by community health workers
      among infants under 6 months in rural Kenya.
AB  - OBJECTIVE: To assess the inter-observer variability and accuracy of Mid Upper Arm
      Circumference (MUAC) and weight-for-length Z score (WFLz) among infants aged <6
      months performed by community health workers (CHWs) in Kilifi District, Kenya.
      METHODS: A cross-sectional repeatability study estimated inter-observer variation
      and accuracy of measurements initially undertaken by an expert anthropometrist,
      nurses and public health technicians. Then, after training, 18 CHWs (three at
      each of six sites) repeatedly measured MUAC, weight and length of infants aged <6
      months. Intra-class correlations (ICCs) and the Pitman's statistic were
      calculated. RESULTS: Among CHWs, ICCs pooled across the six sites (924 infants)
      were 0.96 (95% CI 0.95-0.96) for MUAC and 0.71 (95% CI 0.68-0.74) for WFLz. MUAC
      measures by CHWs differed little from their trainers: the mean difference in MUAC
      was 0.65 mm (95% CI 0.023-1.07), with no significant difference in variance (P =
      0.075). CONCLUSION: Mid Upper Arm Circumference is more reliably measured by CHWs
      than WFLz among infants aged <6 months. Further work is needed to define cut-off
      values based on MUAC's ability to predict mortality among younger infants.

PMID- 22364556
TI  - Calibration of a chemical ionization mass spectrometer for the measurement of
      gaseous sulfuric acid.
AB  - The accurate measurement of the gaseous sulfuric acid concentration is crucial
      within many fields of atmospheric science. Instruments utilizing chemical
      ionization mass spectrometry (CIMS) measuring H(2)SO(4), therefore, require a
      careful calibration. We have set up a calibration source that can provide a
      stable and adjustable concentration of H(2)SO(4). The calibration system
      initiates the production of sulfuric acid through the oxidation of SO(2) by OH.
      The hydroxyl radical is produced by UV photolysis of water vapor. A numerical
      model calculates the H(2)SO(4) concentration provided at the outlet of the
      calibration source. From comparison of this concentration and the signals
      measured by CIMS, a calibration factor is derived. This factor is evaluated to be
      1.1 * 10(10) cm(-3), which is in good agreement with values found in the
      literature for other CIMS instruments measuring H(2)SO(4). The calibration system
      is described in detail and the results are discussed. Because the setup is
      external to the CIMS instrument, it offers the possibility for future CIMS
      intercomparison measurements by providing defined and stable concentrations of
      sulfuric acid.

PMID- 22364557
TI  - Nonparametric inference for median costs with censored data.
AB  - Increasingly, estimations of health care costs are used to evaluate competing
      treatments or to assess the expected expenditures associated with certain
      diseases. In health policy and economics, the primary focus of these estimations
      has been on the mean cost, because the total cost can be derived directly from
      the mean cost, and because information about total resources utilized is highly
      relevant for policymakers. Yet, the median cost also could be important, both as
      an intuitive measure of central tendency in cost distribution and as a subject of
      interest to payers and consumers. In many prospective studies, cost data
      collection is sometimes incomplete for some subjects due to right censoring,
      which typically is caused by loss to follow-up or by limited study duration.
      Censoring poses a unique challenge for cost data analysis because of so-called
      induced informative censoring, in that traditional methods suited for survival
      data generally are invalid in censored cost estimation. In this article, we
      propose methods for estimating the median cost and its confidence interval (CI)
      when data are subject to right censoring. We also consider the estimation of the
      ratio and difference of two median costs and their CIs. These methods can be
      extended to the estimation of other quantiles and other informatively censored
      data. We conduct simulation and real data analysis in order to examine the
      performance of the proposed methods.

PMID- 22364558
TI  - Iron-regulatory gene expression during liver regeneration.
AB  - BACKGROUND: In rat, the first 18-24 h after partial hepatectomy (PH) are
      characterized by an acute-phase reaction, after which liver regeneration
      predominates. Interleukin-6 (IL-6) induces the iron hormone hepcidin, which
      blocks iron uptake and may compromise iron uptake in the growing liver. The
      expressions of hepcidin and the iron-regulatory pathway of hepcidin gene
      expression during the late phase of liver regeneration are unknown. AIM: To
      characterize the expression pattern of hepcidin and the iron-sensing pathway of
      hepcidin regulation during liver regeneration. METHODS: Rats were subjected to PH
      or sham operation. Liver weights, number of S-phase nuclei, and serum levels of
      iron and IL-6 were determined. Messenger-RNA levels of hepcidin, ferritin,
      hemojuvelin, transferrin receptor 1 and 2, HFE, divalent metal transporter 1,
      ferroportin, and ceruloplasmin were determined with qPCR at different time
      points. Protein levels of STAT3 and SMAD4 were determined with western blot.
      RESULTS: During the acute-phase response, IL-6 release induced STAT3 protein and
      hepcidin mRNA, whereas mRNA levels of proteins in the iron-sensing pathway (HFE,
      hemojuvelin, and transferrin receptor 2) decreased. The mRNA levels of proteins
      involved in cellular iron uptake were increased and cellular iron export
      unchanged. During liver regeneration >24 h after PH, gene expressions in the iron
      sensing pathway were continuously suppressed and hepcidin mRNA levels declined 3
      7 days after surgery. CONCLUSIONS: Hepcidin gene expression peaks during the
      acute-phase response, but a sustained down-regulation of the iron-sensing pathway
      of hepcidin regulation gradually reduces hepcidin gene expression until
      regeneration is complete, thereby promoting iron mobilization to the regenerating
      liver.

PMID- 22364561
TI  - Effects of trunk restraint in addition to home-based modified constraint-induced
      movement therapy after stroke: a randomized controlled trial.
AB  - RATIONALE: Upper limb deficits contribute to disabilities after stroke, and
      constraint-induced movement therapy has been recommended to improve functional
      activity. People with stroke excessively move their trunk when reaching and
      grasping objects. Therefore, trunk restraints in addition to constraint-induced
      movement therapy may provide advantages over constraint-induced movement therapy
      alone by promoting both increases in upper limb use and movement recovery.
      Although a pilot study has previously evaluated this combination, the assessors
      were not blinded, thus compromising the validity of the results. AIM: This study
      will test the hypothesis that home-based constraint-induced movement therapy plus
      trunk restraints are superior to constraint-induced movement therapy alone in
      improving strength, function, and participation with chronic stroke patients.
      DESIGN: For this prospective, blinded, randomized clinical trial, people after
      stroke will be randomly allocated into either experimental or control groups. The
      experimental group will undertake three-hours/day of modified constraint-induced
      movement therapy plus trunk restraints to prevent trunk displacements, five
      days/week over two-weeks, while the control group only will undertake the same
      doses of modified constraint-induced movement therapy. At baseline, after two
      weeks of interventions, and four and 12 weeks after the cessation of the
      interventions, researchers blinded to group allocations will collect outcome
      measures. The interventions will be delivered in the individuals' homes by
      trained physical therapists. The constraint-induced movement therapy will include
      shaping, task practice, and the transfer packages. STUDY OUTCOMES: Primary
      outcomes will be the upper limb function (referred amounts and quality of
      movement). Secondary outcomes will be measured for levels of impairments
      (strength and dexterity), activity (reaching kinematics and observed upper limb
      function), and levels of participation (quality of life).

PMID- 22364560
TI  - Oral health-related quality of life and nutritional status of institutionalized
      elderly population aged 60 years and above in Mysore City, India.
AB  - OBJECTIVE: To assess whether oral health-related quality of life (OHRQoL) is
      associated with nutritional status in the institutionalised elderly population of
      Mysore. BACKGROUND: Malnutrition in the elderly has an evident impact on their
      general health and quality of life. Analysis of data of the Geriatric Oral Health
      Assessment Index (GOHAI) and their association with the Mini Nutritional
      Assessment (MNA) results improves our understanding of the complex relationship
      between oral health and malnutrition. MATERIALS AND METHODS: The study was
      conducted among the institutionalised elderly population in Mysore city,
      Karnataka. Data on socio-demographic, oral health status were gathered. OHRQoL
      was evaluated using GOHAI, and malnutrition risk using MNA. RESULTS: Out of 141
      elderly, 41.1% were men and 58.9% were women with mean age of 72.2 +/-7.5 years.
      Mean GOHAI score was 47.03 +/- 9.2, with 69.5% had low perception of oral health.
      Mean MNA score was 9.91 +/- 2.4, 15.6% were malnourished, 52.5% were at risk of
      malnutrition and 31.9% were adequately nourished. A strong association was found
      between the mean GOHAI and MNA scores. CONCLUSION:  Oral health-related quality
      of life was associated with nutritional deficit, and it requires a greater
      integration between dentistry and nutrition in the health promotion of older
      adults.

PMID- 22364559
TI  - Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver
      disease progression.
AB  - Our understanding of the mechanisms by which nonalcoholic fatty liver disease
      (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very
      limited. Despite the growing number of studies linking the disease with altered
      serum metabolite levels, an obstacle to the development of metabolome-based NAFLD
      predictors has been the lack of large cohort data from biopsy-proven patients
      matched for key metabolic features such as obesity. We studied 467 biopsied
      individuals with normal liver histology (n=90) or diagnosed with NAFLD
      (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all
      patients) and validation (20% of all patients) groups. Qualitative determinations
      of 540 serum metabolite variables were performed using ultraperformance liquid
      chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was
      dependent on patient body-mass index (BMI), suggesting that the NAFLD
      pathogenesis mechanism may be quite different depending on an individual's level
      of obesity. A BMI-stratified multivariate model based on the NAFLD serum
      metabolic profile was used to separate patients with and without NASH. The area
      under the receiver operating characteristic curve was 0.87 in the estimation and
      0.85 in the validation group. The cutoff (0.54) corresponding to maximum average
      diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a
      specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present
      data, indicating that a BMI-dependent serum metabolic profile may be able to
      reliably distinguish NASH from steatosis patients, have significant implications
      for the development of NASH biomarkers and potential novel targets for
      therapeutic intervention.

PMID- 22364562
TI  - Rationale and procedures for nesting semi-structured interviews in surveys or
      censuses.
AB  - Demographers who use survey data and census data from health and demographic
      surveillance areas can gain substantially from expanding their repertoire of
      methods to make use of qualitative methods. Similarly, those who conduct and
      analyse data primarily from semi-structured interviews or focus groups can
      benefit from information provided by survey research. This paper presents a
      systematic mixed-methods model-data-linked nested studies-for sampling
      respondents for semi-structured interviews from survey or census lists. The paper
      outlines how to conduct these types of study, and their technical and analytical
      advantages. It highlights the benefits of building on a strong foundation, the
      ability to compare samples, and the expansion of the range of evidence for, or
      against, the validity of the substantive findings. Case studies from two data
      linked nested projects-in Malawi and South Africa-are used to describe in detail
      the nested-study approach.

PMID- 22364563
TI  - Unsensitized photochemical hydrogen production catalyzed by diiron hydrides.
AB  - The diiron hydride [(MU-H)Fe(2)(pdt)(CO)(4)(dppv)](+) ([H2](+), dppv = cis-1,2
      C(2)H(2)(PPh(2))(2)) is shown to be an effective photocatalyst for the H(2)
      evolution reaction (HER). These experiments establish the role of hydrides in
      photocatalysis by biomimetic diiron complexes. Trends in redox potentials
      suggests that other unsymmetrically substituted diiron hydrides are promising
      catalysts. Unlike previous catalysts for photo-HER, [H2](+) functions without
      sensitizers: irradiation of [H2](+) in the presence of triflic acid (HOTf)
      efficiently affords H(2). Instead of sacrificial electron donors, ferrocenes can
      be used as recyclable electron donors for the photocatalyzed HER, resulting in 4
      turnovers.

PMID- 22364564
TI  - Minimizing defects in polymer-based Langmuir-Blodgett monolayers and bilayers via
      gluing.
AB  - Polymeric surfactants were prepared by quaternization of poly(4
      chloromethylstyrene) with N,N-dimethyl-N-n-dodecylamine and N,N-dimethyl-N-n
      octylamine to give 1 and 2, respectively. Each of these polymers formed stable
      monolayers at the air/water interface. Injection of poly(acrylic acid) (PAA)
      beneath the surface of these films led to a substantial increase in their
      cohesiveness (i.e., "gluing"), as evidenced by a dramatic increase in their
      surface viscosity. Examination of monolayers of 1 by atomic force microscopy,
      after being transferred to silicon wafers that were surface-modified with n
      octadecyltrichlorosilane, showed that the presence of PAA leads to intact film.
      In contrast, transfer of unglued monolayers resulted in poor coverage. Comparison
      of the barrier properties of single glued and unglued LB bilayers formed in the
      presence and in the absence of PAA have shown that PAA minimizes defect formation
      within these ultrathin assemblies.

PMID- 22364565
TI  - Evaluation of early regenerative processes in a preclinical pig model of acute
      kidney injury.
AB  - Renal failure due to ischemic injury is a common denominator of various clinical
      situations in critically ill patients. This study was designed to characterize
      the TPSO/Cholesterol synthesis and cell division pathways in response to
      different levels of ischemia. Porcine kidneys were subjected to either 60 min
      warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4 degrees
      C (CS), or both conditions (WI+CS), pathway activation and function were
      evaluated at 3 h, 3 and 7 days after reperfusion. CS combined to WI affects renal
      functions indicating a high degree of injury. During the first week of
      reperfusion, renal levels of free and esterified cholesterol, major cellular
      components, increased in CS group with an attenuated production when WI was
      associated. CS and WI+CS groups exhibited an elevated expression of cell cycle
      induction markers such as PCNA and stathmin. TSPO expression was highest in
      groups with the lowest injury, and correlated with kidney outcome, revealing its
      potential for diagnosis.

PMID- 22364566
TI  - Pipestelides A-C: cyclodepsipeptides from the Pacific marine sponge Pipestela
      candelabra.
AB  - Pipestelides A-C (2-4) are three new NRPS-PKS hybrid macrolides containing
      uncommon moieties, isolated from the Pacific marine sponge Pipestela candelabra.
      Their structures were elucidated on the basis of spectroscopic data. These
      cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka
      jasplakinolide) (1) by chemical modification of the building blocks of the
      polyketide or peptide chains. Pipestelides A-C (2-4) contain a bromotyrosine [3
      amino-3-(bromo-4-hydroxyphenyl)propanoic acid] unit, a polypropionate with a Z
      double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift
      assignments are provided for the co-isolated known jasplakinolide C(a) (5). In
      addition, compounds 2 and 3 exhibited cytotoxic activities in the micromolar
      range.

PMID- 22364567
TI  - Clinical and economic outcomes associated with National Kidney Foundation
      guideline-concordant oral antidiabetic drug treatment among type 2 diabetes
      patients with chronic kidney disease.
AB  - OBJECTIVE: To assess outcomes associated with oral anti-diabetic drug (OAD)
      treatment concordant with guidelines from the National Kidney Foundation (NKF)
      among type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD).
      METHODS: Electronic health record data between 1/1/2005 and 10/31/2010 provided
      by an integrated health system were analyzed. T2DM patients were selected based
      on diagnosis from the health record. Patients with stages 3-5 CKD based on
      diagnosis or lab results were further identified with the date of first indicated
      CKD set as index date. Patients who had a medication order of OADs within three
      months of the index date were included. Patients were considered non-guideline
      concordant if prescribed OADs that were recommended to be avoided or if they
      required dosage adjustment, but were unadjusted. Glycemic control, hospital
      admissions, and costs of encounters were assessed over a 12-month post-index
      period, and hypoglycemic events were evaluated until loss of follow-up.
      Regression analyses were performed, adjusting for patient demographic and
      clinical characteristics. RESULTS: Among 6058 patients (mean age: 70; 42% male),
      45% were not [corrected] guideline-concordant. After adjusting for patient
      characteristics, guideline-concordant patients had a lower risk for hypoglycemic
      events (HR: 0.72; 95% CI: 0.62-0.83), were less likely to have a hospital
      admission (OR: 0.87; 95% CI: 0.77-0.98), and more likely to have glycemic control
      (OR: 1.64, 95% CI: 1.46-1.84). Non-guideline-concordant patients had annual
      encounter costs of 1.10 times those of guideline-concordant patients (marginal
      cost = $731; P = 0.04). LIMITATIONS: Unobservable confounders may still exist and
      bias the results; therefore, findings should be interpreted as associations
      instead of causations. Findings were based on a single integrated health system
      and may not be generalizable to larger populations. CONCLUSION: The findings of
      this exploratory study suggest that guideline-concordant treatment may yield
      better clinical and economic outcomes. Future research with a better controlled
      design is warranted to confirm these preliminary findings.

PMID- 22364568
TI  - Patient survival and healthcare utilization costs after diagnosis of triple
      negative breast cancer in a United States managed care cancer registry.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) makes up 10-17% of all breast
      cancers and, due to lack of receptor expression, is unresponsive to therapies
      that target hormonal receptors or HER2. Unique in its tumor aggression and high
      rates of recurrence, TNBC is less likely to be detected by mammogram and has a
      poorer prognosis than other breast cancer subtypes (non-TNBC). OBJECTIVES: To
      examine the survival, healthcare utilization, and healthcare cost for women with
      TNBC compared with non-TNBC breast cancer. METHODS: The study population was
      derived from a US managed care cancer registry linked to health insurance claims
      and social security mortality data. Based on initial type and stage at diagnosis,
      patients were divided into two cohorts: patients with TNBC and those with non
      TNBC. Records were analyzed from initial diagnosis until death, disenrollment, or
      end of observation period. Survival and annual healthcare utilization and costs
      were estimated and compared between cohorts after adjusting for baseline
      demographic characteristics, comorbidities, and prior resource use. Subgroup
      analyses were performed in patients diagnosed with stage I-III and IV breast
      cancer. RESULTS: The study included women diagnosed with TNBC (n = 450) and non
      TNBC (n = 1807). Median follow-up time for all patients was 716 days (688.5 and
      733 days for TNBC and non-TNBC patients, respectively). After initial diagnosis,
      overall mortality risk for the TNBC cohort was twice as high as the non-TNBC
      cohort (HR = 2.02, p < 0.0001). Patients with TNBC had more annual
      hospitalizations, hospitalized days, and number of emergency room visits relative
      to non-TNBC. Despite similar annual total healthcare costs, adjusted inpatient
      costs for patients with non-TNBC averaged 77% higher ($8395 vs. $4745, p <
      0.0001). Furthermore, payer reimbursements were higher for TNBC than non-TNBC
      patients ($8213 vs. $4486, p < 0.0001). CONCLUSIONS: While it does not control
      for race or socioeconomic status, this study found that in a US managed care
      setting, patients with TNBC compared with non-TNBC have significantly shorter
      survival, accompanied by higher inpatient utilization and healthcare costs.

PMID- 22364569
TI  - Analysis of volatile organic compounds released from human lung cancer cells and
      from the urine of tumor-bearing mice.
AB  - BACKGROUNDS: A potential strategy for the diagnosis of lung cancer is to exploit
      the distinct metabolic signature of this disease by way of biomarkers found in
      different sample types. In this study, we investigated whether specific volatile
      organic compounds (VOCs) could be detected in the culture medium of the lung
      cancer cell line A549 in addition to the urine of mice implanted with A549 cells.
      RESULTS: Several VOCs were found at significantly increased or decreased
      concentrations in the headspace of the A549 cell culture medium as compared with
      the culture medium of two normal lung cell lines. We also analyzed the urine of
      mice implanted with A549 cells and several VOCs were also found to be
      significantly increased or decreased relative to urine obtained from control
      mice. It was also revealed that seven VOCs were found at increased concentrations
      in both sample types. These compounds were found to be dimethyl succinate, 2
      pentanone, phenol, 2-methylpyrazine, 2-hexanone, 2-butanone and acetophenone.
      CONCLUSIONS: Both sample types produce distinct biomarker profiles, and VOCs have
      potential to distinguish between true- and false-positive screens for lung
      cancer.

PMID- 22364571
TI  - Quantitative structure-reactivity study of electrochemical oxidation of phenolic
      compounds at the SnO2-based electrode.
AB  - In the present study, the electrochemical oxidation of 22 phenolic compounds was
      systemically examined at the RuO(2)-SnO(2)-Sb(2)O(5) electrode to elucidate the
      inherent structure-reactivity correlation. The oxidation process was monitored in
      situ by UV-vis spectroscopy. A variety of substituents (e.g., -CH(3), -NH(2), 
      Cl, -OH, -COOH, -NO(2), -CHO) were employed in order to cover various possible
      electronic effects. Our experimental results revealed that the relationship
      between the Hammett constant and rate constant for the electrochemical oxidation
      of phenolic compounds at the RuO(2)-SnO(2)-Sb(2)O(5) electrode was different from
      the results obtained at a platinum electrode. The substituted phenols with
      electron-withdrawing groups were electrochemically oxidized more rapidly than
      those with electron-donating groups. To decipher the effects of physiochemical
      properties on the electrochemical reactivity of phenolic compounds, 140 molecular
      descriptors were calculated and assessed for each phenolic compound; a
      quantitative structure property relationship (QSPR) model was developed.
      Correlations between the rate constants and quantum properties of the phenolic
      compounds were achieved using partial least-squares (PLS) analysis. The most
      crucial quantum descriptors responsible for the electrochemical reactivity of
      phenolic compounds were determined to be E(HOMO), chemical potential, total
      dipole, quadrupoles, subgraph counts, relative positive charged surface area, and
      pK(a). The proposed QSPR model was based on the quantum descriptors derived from
      the whole molecule, providing lucid explanation and effective prediction of the
      electrochemical reactivity of various phenolic compounds.

PMID- 22364570
TI  - Contributions of mass spectrometry-based proteomics to defining cellular
      mechanisms and diagnostic markers for systemic lupus erythematosus.
AB  - Systematic lupus erythematosus (SLE) is a complex disease for which molecular
      diagnostics are limited and pathogenesis is not clearly understood. Important
      information is provided in this regard by identification and characterization of
      more specific molecular and cellular targets in SLE immune cells and target
      tissue and markers of early-onset and effective response to treatment of SLE
      complications. In recent years, advances in proteomic technologies and
      applications have facilitated such discoveries. Here we provide a review of
      insights into SLE pathogenesis, diagnosis and treatment that have been provided
      by mass spectrometry-based proteomic approaches.

PMID- 22364572
TI  - Cytocompatibility of the ready-to-use bioceramic putty repair cement iRoot BP
      Plus with primary human osteoblasts.
AB  - AIM: To verify the in vitro cytocompatibility of iRoot BP Plus (iRoot) and to
      compare it with White ProRoot MTA (MTA). METHODOLOGY: Thirty-six human maxillary
      incisor root canals were prepared using a step-back flaring technique. The apical
      3 mm was resected perpendicular to the long axis at the roots, and root-end
      cavities were prepared with the aid of an ultrasonic device plus a diamond
      retrotip with continuous irrigation using water, producing standardized
      preparations. After that, the root-end cavities were filled with iRoot or MTA,
      and each root was exposed to cell culture media for 24 or 48 h. Human osteoblast
      cells were exposed to the extracts thus obtained, and a multiparametric cell
      viability assay was performed, evaluating mitochondrial activity, membrane
      integrity and cell density. The results were analysed by one-way analysis of
      variance, complemented with the Duncan post-test (P < 0.05). RESULTS: Cells
      exposed to MTA revealed a cytocompatibility pattern similar to the untreated
      cells (negative control), at both experimental times (P > 0.05). iRoot, however,
      promoted a significantly poorer viability than MTA and the control, after 48 h of
      exposure (P < 0.001). Nevertheless, iRoot did not induce critical cytotoxic
      effects because cell viability remained higher than 70% of the control group in
      most tests performed. CONCLUSION: iRoot and MTA were biocompatible and did not
      induce critical cytotoxic effects.

PMID- 22364573
TI  - Interaction of tea polyphenols and food constituents with model gut epithelia:
      the protective role of the mucus gel layer.
AB  - The luminal surface of the gastrointestinal tract is covered by a mucus gel layer
      that acts to protect gut epithelial cells from the harsh luminal environment.
      This study investigated the use of two human colonic adenocarcinoma cell lines,
      HT29-MTX-E12 and HT29, as a model to mimic gut epithelium with and without a
      mucus gel layer. The effect of adding the tea polyphenols epigallocatechin
      gallate (EGCG) and epicatechin (EC) to the cells with subsequent examination of
      cell morphology and viability was assessed. EGCG, at the concentrations tested,
      was very toxic to the HT29 cells, but less toxic to the HT29-MTX-E12 cells,
      suggesting that the mucus gel layer on the HT29-MTX-E12 cells can protect the
      cells against EGCG toxicity. In contrast, EC had no effect on the viability of
      either the HT29 or HT29-MTX-E12 cells, suggesting that proteins within the mucus
      gel layer on the apical surface of gut epithelial cells may bind to the galloyl
      ring of EGCG. The effect of adding food-related ingredients with the ability to
      complex with EGCG, beta-casein and maltodextrin, on cell viability was also
      examined. The presence of beta-casein was very effective in protecting the cells
      against the toxicity effect of EGCG, but maltodextrin, at the concentration
      tested, was less effective in protecting against this toxicity. In conclusion,
      the results demonstrate that the mucus gel layer on HT29 human colonic
      adenocarcinoma cells may protect these cells against EGCG toxicity. In addition,
      the data showing reduced toxicity of EC compared to that of EGCG suggest that the
      cytotoxic effects of high polyphenol levels may be associated with the ability of
      polyphenols to interact with cellular proteins and mucins.

PMID- 22364575
TI  - Philosophy and the practice of Bayesian statistics.
AB  - A substantial school in the philosophy of science identifies Bayesian inference
      with inductive inference and even rationality as such, and seems to be
      strengthened by the rise and practical success of Bayesian statistics. We argue
      that the most successful forms of Bayesian statistics do not actually support
      that particular philosophy but rather accord much better with sophisticated forms
      of hypothetico-deductivism. We examine the actual role played by prior
      distributions in Bayesian models, and the crucial aspects of model checking and
      model revision, which fall outside the scope of Bayesian confirmation theory. We
      draw on the literature on the consistency of Bayesian updating and also on our
      experience of applied work in social science. Clarity about these matters should
      benefit not just philosophy of science, but also statistical practice. At best,
      the inductivist view has encouraged researchers to fit and compare models without
      checking them; at worst, theorists have actively discouraged practitioners from
      performing model checking because it does not fit into their framework.

PMID- 22364576
TI  - Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal
      differentiation in a patient with von Hippel-Lindau disease.
AB  - There are controversies regarding the histogenesis of stromal cells of
      hemangioblastoma, and no hypothesis has conclusively been proven. We report a
      case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau
      disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were
      located within both sides of the cerebellar hemisphere. Histologically, only
      small areas showing the typical morphology of hemangioblastoma were recognized in
      masses. Most areas of masses were composed of cohesive epithelioid tumor cells
      with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were
      arranged around blood vessels, exhibiting perivascular anuclear zone structures
      like ependymoma. The epithelioid tumor cells were diffusely positive for
      vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial
      membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid
      droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor
      cells under an electron microscope. A diagnosis of epithelioid cellular
      hemangioblastoma with possible ependymal differentiation (WHO grade I) was made.
      To our knowledge, only a few cases of hemangioblastoma show epithelioid
      appearance or EMA immunoreactivity. The present case indicates that the stromal
      cells of hemangioblastoma might originate from primitive neuroectodermal cells,
      and they have the capacity to show a distinctive sign of glial or ependymal
      differentiation.

PMID- 22364577
TI  - Validation of the Reflux, Airway and Sleep Questionnaire (RASQ).
AB  - BACKGROUND: Airway symptoms and sleeplessness in patients with gastroesophageal
      reflux disease (GERD) may be of importance. This study validates a new
      questionnaire dealing with such symptoms. MATERIAL AND METHODS: The Reflux,
      Airway and Sleep Questionnaire (RASQ) is self-administered, asks about 18
      symptoms or diagnoses possibly related to GERD answered on a seven-point Likert
      scale and with a 1-year recall period. There are questions about
      heartburn/regurgitation, sleeplessness, snoring, pneumonia, and upper airway
      infections, as well as various bronchial and laryngeal symptoms. The study
      included 305 patients diagnosed with GERD (n = 65), laryngitis (n = 32), asthma
      (n = 30), chronic obstructive pulmonary disease (n = 45), acute bronchitis (n =
      39), pneumonia (n = 42), or upper airway infection (n = 52) during the last year,
      and 708 matched healthy controls. Concurrent validity was based on comparisons
      between patients and controls. Convergent validity for sleeplessness and snoring
      were tested by comparing the RASQ with the Pittsburgh Sleep Quality Index (PSQI)
      and the Epworth Sleepiness Scale (ESS). Test-retest reliability was examined in
      patients with GERD with stable symptoms (n = 29). RESULTS: Response rates were
      64% for patients and 55% for controls. Scores for RASQ as a total and all
      subscales were significantly higher in patients than in controls. Sleeplessness
      scores correlated significantly to the global PSQI score. Snoring correlated
      significantly with both the ESS and relevant aspects of the PSQI. Test-retest
      reliability and Cronbach's alpha were satisfactory, with coefficients ranging
      between 0.65-0.95 and 0.88-0.92, respectively. CONCLUSION: The RASQ appears to be
      well suited for measuring typical reflux symptoms as well as airway symptoms and
      sleep disturbances.

PMID- 22364578
TI  - Socioeconomic status and lifetime risk for workplace eye injury reported by a us
      population aged 50 years and over.
AB  - PURPOSE: To examine whether socioeconomic status, as measured by educational
      attainment and annual household income, is associated with lifetime risk for
      workplace eye injury in a large US population. METHODS: In analyses of data from
      the Behavioral Risk Factor Surveillance System (2005-2007, N = 43,510), we used
      logistic regression analysis and propensity score matching to assess associations
      between socioeconomic measures and lifetime risk for workplace eye injury among
      those aged >=50 years. RESULTS: The lifetime prevalence of self-reported
      workplace eye injury was significantly higher among men (13.5%) than women (2.6%)
      (P < 0.001). After adjusting for age, race/ethnicity, eye care insurance, health
      status, and risk-taking behaviors, men with less than high school education
      (adjusted odds ratio [OR] = 2.24, 95% CI: 1.74-2.87) or high school education
      (adjusted OR = 1.92, 95% CI: 1.57-2.33) were more likely to report having had a
      lifetime workplace eye injury than those with more than a high school education.
      Men with an annual household income <$15,000 were also more likely to report
      having had a lifetime workplace eye injury than those whose income was >$50,000
      (adjusted OR = 1.44, 95% CI: 1.07-1.95). After adjusting for other factors, no
      statistically significant associations between education, income, and lifetime
      workplace eye injury were found among women. CONCLUSIONS: Socioeconomic status
      was associated with lifetime risk for workplace eye injury among men but not
      women. Greater public awareness of individual and societal impacts of workplace
      eye injuries, especially among socioeconomically disadvantaged men, could help
      support efforts to develop a coordinated prevention strategy to minimize
      avoidable workplace eye injuries.

PMID- 22364579
TI  - Hypoglycaemia, analogue insulins; prescribing cost or quality of life?

PMID- 22364580
TI  - Glucose-lowering treatment and clinical results in 163 121 patients with type 2
      diabetes: an observational study from the Swedish national diabetes register.
AB  - AIMS: To analyse clinical characteristics and treatment results in unselected
      type 2 diabetes mellitus (T2DM) patients, with non-pharmacological treatment as
      well as the most commonly used pharmacological glucose-lowering treatment
      regimens, in everyday clinical practice. METHODS: In this population-based cross
      sectional study, information was linked from the Swedish National Diabetes
      Register, Prescribed Drug Register and Patient Register. T2DM patients with non
      pharmacological treatment and T2DM patients continuously using the 12 most common
      pharmacological treatment regimens were included in the study (n = 163121).
      RESULTS: There were statistically significant differences in clinical
      characteristics between the groups. Patients with insulin-based treatment
      regimens had the longest duration of diabetes and more cardiovascular risk
      factors than the T2DM-population in general. The proportion of patients reaching
      HbA1c <= 7% varied between 70.1% (metformin) and 25.0% [premixed insulin (PMI) +
      SU) in patients with pharmacological treatment. 84.8% of the patients with non
      pharmacological treatment reached target. Compared to patients on metformin,
      patients on other pharmacological treatments had a lower likelihood, with hazard
      ratios ranging from 0.58; 95% confidence interval (CI), 0.54-0.63 to 0.97;0.94
      0.99, of having HbA1c <= 7% (adjusted for covariates). Patients on insulin-based
      treatments had the lowest likelihood, while non-pharmacological treatment was
      associated with an increased likelihood of having HbA1c <= 7%. CONCLUSION: This
      nation-wide study shows insufficiently reached treatment goals for haemoglobin
      A1c (HbA1c) in all treatment groups. Patients on insulin-based treatment regimens
      had the longest duration of diabetes, more cardiovascular risk factors and the
      highest proportions of patients not reaching HbA1c target.

PMID- 22364581
TI  - Learning separate visual representations of independently rotating objects.
AB  - Individual cells that respond preferentially to particular objects have been
      found in the ventral visual pathway. How the brain is able to develop neurons
      that exhibit these object selective responses poses a significant challenge for
      computational models of object recognition. Typically, many objects make up a
      complex natural scene and are never presented in isolation. Nonetheless, the
      visual system is able to build invariant object selective responses. In this
      paper, we present a model of the ventral visual stream, VisNet, which can solve
      the problem of learning object selective representations even when multiple
      objects are always present during training. Past research with the VisNet model
      has shown that the network can operate successfully in a similar training
      paradigm, but only when training comprises many different object pairs. Numerous
      pairings are required for statistical decoupling between objects. In this
      research, we show for the first time that VisNet is capable of utilizing the
      statistics inherent in independent rotation to form object selective
      representations when training with just two objects, always presented together.
      Crucially, our results show that in a dependent rotation paradigm, the model
      fails to build object selective representations and responds as if the two
      objects are in fact one. If the objects begin to rotate independently, the
      network forms representations for each object separately.

PMID- 22364582
TI  - Total lymphocyte count is a reliable surrogate marker for CD4 cell counts after
      the first year of antiretroviral therapy: data from an Indonesian cohort study.
AB  - Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate
      marker for CD4 cells in HIV-infected patients not receiving antiretroviral
      therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating
      the immunological response to ART. In a cohort of patients in Indonesia TLC, if
      measured after at least 1-year ART, correctly identified patients with <200 CD4
      cells, and reliably excluded immunological failure, obviating the need for CD4
      cell measurement in 43% of patients.

PMID- 22364584
TI  - Identification and characterization of mesenchymal stem cells derived from the
      trabecular meshwork of the human eye.
AB  - Mesenchymal stem cells (MSC) have been isolated from several adult human tissues.
      Their propensity to differentiate into cell types of connective tissue, such as
      osteocytes, chondrocytes, and adipocytes, suggests that MSC may function as a
      reserve of progenitor cells that repair and maintain healthy adult tissues.
      Dysfunction of the trabecular meshwork (TM), a connective tissue at the anterior
      region of the human eye that regulates intraocular pressure, plays a major role
      in the pathogenesis of glaucoma. The mechanobiology and pharmacological aspects
      of the TM tissue have been relatively well studied in disease states. Less well
      understood is if there are progenitor cells within the TM that contribute to
      maintenance of this tissue. In this study, we have identified and characterized
      an expandable population of cells that have stem cell-like properties. In
      particular, these cells express the markers CD73, CD90, and CD105, which are
      typically associated with MSC. Thus, we have named these cells TM-MSC. As further
      evidence that these cells are MSC, they were differentiated in vitro into
      adipocytes, osteocytes, and chondrocytes. Through genomic characterization, we
      show that TM-MSC have gene expression patterns most similar to MSC derived from
      other tissues. TM-MSC express genes found on adult TM tissue, suggesting that TM
      MSC are progenitor cells that serve to maintain a healthy TM.

PMID- 22364583
TI  - Proteomic analysis of ripening tomato fruit infected by Botrytis cinerea.
AB  - Botrytis cinerea, a model necrotrophic fungal pathogen that causes gray mold as
      it infects different organs on more than 200 plant species, is a significant
      contributor to postharvest rot in fresh fruit and vegetables, including tomatoes.
      By describing host and pathogen proteomes simultaneously in infected tissues, the
      plant proteins that provide resistance and allow susceptibility and the pathogen
      proteins that promote colonization and facilitate quiescence can be identified.
      This study characterizes fruit and fungal proteins solubilized in the B. cinerea
      tomato interaction using shotgun proteomics. Mature green, red ripe wild type and
      ripening inhibited (rin) mutant tomato fruit were infected with B. cinerea
      B05.10, and the fruit and fungal proteomes were identified concurrently 3 days
      postinfection. One hundred eighty-six tomato proteins were identified in common
      among red ripe and red ripe-equivalent ripening inhibited (rin) mutant tomato
      fruit infected by B. cinerea. However, the limited infections by B. cinerea of
      mature green wild type fruit resulted in 25 and 33% fewer defense-related tomato
      proteins than in red and rin fruit, respectively. In contrast, the ripening stage
      of genotype of the fruit infected did not affect the secreted proteomes of B.
      cinerea. The composition of the collected proteins populations and the putative
      functions of the identified proteins argue for their role in plant-pathogen
      interactions.

PMID- 22364585
TI  - Could muscle deformity in children with spastic cerebral palsy be related to an
      impairment of muscle growth and altered adaptation?
AB  - Skeletal muscle deformity is common in children with spastic cerebral palsy (CP),
      but the underlying mechanisms are unclear. This review explores some possible
      factors which may influence the development of muscle deformity in CP. Normal
      muscle function and growth appear to depend on the interaction of neuronal,
      endocrinal, nutritional, and mechanical factors, and also on the development of
      an appropriate balance between muscle protein synthesis and degradation, and
      between the development of contractile and non-contractile components. In this
      context, the changes seen in muscle in children with CP are reviewed and
      discussed. It is suggested that the development of muscle deformity in children
      with CP may be related to a multifactorial impairment of muscle growth, on which
      adaptation of the extracellular matrix due to altered loading may be imposed.

PMID- 22364586
TI  - Sex after stroke: a content analysis of printable educational materials available
      online.
AB  - BACKGROUND: Providing written educational materials to stroke survivors is a key
      recommendation in many international stroke guidelines. Yet, sexual concerns are
      generally overlooked in current stroke rehabilitation and the content of
      educational materials on sexual concerns has not been analyzed nor evaluated in
      published stroke research. AIM: The aim of this study was to identify, describe,
      and analyze printable educational materials on sexual concerns that are available
      online and easily shared with stroke survivors. METHOD: Google search engine was
      used to locate printable educational materials from the Internet using a search
      term strategy of 35 phrases that were piloted for accuracy. The content of
      eligible materials was analyzed using NVivo software to produce both enumerative
      and thematic data. RESULTS: Nine educational materials from reputable
      organizations were included with an average length of seven pages and 1445 words
      (total 61 pages, 13 000 words). The content of the materials was similar and
      covered three main content areas: problems experienced after stroke: 30% coverage
      suggested solutions: 32% coverage, and reassurance: 9% coverage. Content
      describing potential problems reflected published research, but solutions and
      reassurance were general, nonspecific, and often not supported by evidence.
      CONCLUSIONS: Educational materials on sex after stroke may be helpful for health
      professionals, stroke survivors, and their partners, yet some messages appear to
      discourage recovery. Educators, health professionals, and organizations can use
      this analysis to evaluate their own educational resources and create resources
      that better address the sexual concerns of stroke survivors and their partners.

PMID- 22364588
TI  - Light traps fail to estimate reliable malaria mosquito biting rates on Bioko
      Island, Equatorial Guinea.
AB  - BACKGROUND: The human biting rate (HBR), an important parameter for assessing
      malaria transmission and evaluating vector control interventions, is commonly
      estimated by human landing collections (HLC). Although intense efforts have been
      made to find alternative non-exposure mosquito collection methods, HLC remains
      the standard for providing reliable and consistent HBRs. The aim of this study
      was to assess the relationship between human landing and light trap collections
      (LTC), in an attempt to estimate operationally feasible conversion factors
      between the two. The study was conducted as part of the operational research
      component of the Bioko Island Malaria Control Project (BIMCP), Equatorial Guinea.
      METHODS: Malaria mosquitoes were collected indoors and outdoors by HLCs and LTCs
      in three villages on Bioko Island, Equatorial Guinea during five bimonthly
      collections in 2009. Indoor light traps were suspended adjacent to occupied long
      lasting, insecticide-treated bed nets. Outdoor light traps were placed close to
      the outer wall under the roof of the collection house. Collected specimens were
      subjected to DNA extraction and diagnostic PCR to identify species within the
      Anopheles gambiae complex. Data were analysed by simple regression of log
      transformed values and by Bayesian regression analysis. RESULTS: There was a poor
      correlation between the two collection methods. Results varied by location,
      venue, month, house, but also by the statistical method used. The more robust
      Bayesian analyses indicated non-linear relationships and relative sampling
      efficiencies being density dependent for the indoor collections, implying that
      straight-forward and simple conversion factors could not be calculated for any of
      the locations. Outdoor LTC:HLC relationships were weak, but could be estimated at
      0.10 and 0.07 for each of two locations. CONCLUSIONS: Light trap collections in
      combination with bed nets are not recommended as a reliable method to assess
      human biting rates on Bioko Island. Different statistical analyses methods give
      variable and inconsistent results. Substantial variation in collection methods
      prevents the determination of reliable and operationally feasible conversion
      factors for both indoor and outdoor data. Until improved mosquito collection
      methods are developed that can provide reliable and unbiased HBR estimates, HLCs
      should continue to serve as the reference method for HBR estimation.

PMID- 22364589
TI  - Mesiobuccal root resection in endodontic-periodontal combined lesions.
AB  - AIM: To present two successful cases involving management of endodontic
      periodontal combined lesions with root resection and guided tissue regeneration
      (GTR) therapy. SUMMARY: Mesiobuccal resection surgery was performed concomitant
      with GTR therapy to manage endodontic-periodontal combined lesions on teeth 17
      and 26. The increased mobility after the periodontal surgery gradually decreased
      during the healing period. At 15 and 20 month follow-ups, respectively, the teeth
      showed no mobility, 2-3 mm pocket depths and no further bone loss. KEY LEARNING
      POINTS: Treatment of periodontally involved maxillary teeth creates unique
      challenges, given the presence of furcations, root proximities and the maxillary
      sinus. Root resection combined with GTR therapy can enable tooth maintenance with
      a good long-term prognosis.

PMID- 22364590
TI  - Fluorescence probing of the temperature-induced phase transition in a glycolipid
      self-assembly: hexagonal <-> micellar and cubic <-> lamellar.
AB  - Water-driven self-assembly of lipids displays a variety of liquid crystalline
      phases that are crucial for membrane functions. Herein, we characterize the
      temperature-induced phase transitions in two compositions of an aqueous self
      assembly system of the octyl beta-D-glucoside (betaGlcOC(8)) system, using steady
      state and time-resolved fluorescence measurements. The phase transitions
      hexagonal <-> micellar and cubic <-> lamellar were investigated using tryptophan
      (Trp) and two of its ester derivatives (Trp-C(4) and Trp-C(8)) to probe the polar
      headgroup region and pyrene to probe the hydrophobic tail region. The polarity of
      the headgroup region was estimated to be close to that of simple alcohols
      (methanol and ethanol) for all phases. The pyrene fluorescence indicates that the
      pyrene molecules are dispersed among the tails of the hydrophobic region, yet
      remain in close proximity to the polar head groups. Comparing the present results
      with our previously reported one for betaMaltoOC(12), increasing the tail length
      of the hexagonal phase from C(8) to C(12) leads to less interaction with pyrene,
      which is attributed to the more random and wobbling motion of the longer alkyl
      tail. We measured a reduction (more hydrophobic) in the ratio of the vibronic
      peak intensities of pyrene (I(1)/I(3)) for the lamellar phase compared to that of
      the cubic phase. The higher polarity in the cubic phase can be correlated to the
      nature of its interface, which curves toward the bulk water. This geometry also
      explains the slight reduction in polarity of the headgroup region compared to the
      other phases. Upon the addition of Trp-C(8), the fluorescence lifetime of pyrene
      is reduced by 28% in the lamellar and cubic phases, whereas the I(1)/I(3) value
      is only slightly reduced. The results reflect the dominant role of dynamic
      interaction mechanism between the C(8) chain of Trp-C(8) and pyrene. This
      mechanism may be important for these two phases since they participate in the
      process of membrane fusion. Both lipid compositions show completely reversible
      temperature-induced phase transitions, reflecting the thermodynamic equilibrium
      structures of their mesophases. Probing both regions of the different lipid
      phases reveals a large degree of heterogeneity and flexibility of the lipid self
      assembly. These properties are crucial for carrying out different biological
      functions such as the ability to accommodate various molecular sizes.

PMID- 22364591
TI  - Transmission and strain variation of Shigella flexneri 4a after mass prophylaxis
      in a long-stay psychiatric centre.
AB  - Shigella flexneri 4a caused sustained outbreaks in a large long-stay psychiatric
      centre, Taiwan, 2001-2006. Trimethoprim-sulphamethoxazole (SXT) prophylaxis was
      administered in 2004. We recovered 108 S. flexneri 4a isolates from 83
      symptomatic (including one caregiver) and 12 asymptomatic subjects (11 contacts,
      one caregiver). The isolates were classified into eight antibiogram types and 15
      genotypes (six clusters) by using antimicrobial susceptibility testing and pulsed
      field gel electrophoresis of NotI-digested DNA, respectively. These
      characteristics altered significantly after SXT prophylaxis (P < 0.05), with
      concomitant emergence of SXT-resistant isolates in two antibiogram types. P01 (n
      = 71), the predominant epidemic genotype, caused infection in two caregivers and
      five patients under their care; two P01 isolates were recovered from the same
      patient 6 months apart. These results indicate the importance of sustained person
      to-person transmission of S. flexneri 4a by long-term convalescent, asymptomatic
      or caregiver carriers, and support the emergence of SXT-resistant strains
      following selective pressure by SXT prophylaxis.

PMID- 22364593
TI  - Insights to the clarification of sugar cane juice expressed from sugar cane stalk
      and trash.
AB  - Processing of juice expressed from green sugar cane containing all the trash
      (i.e., tops and leaves, the nonstalk component) of the sugar cane plant during
      sugar manufacture has been reported to lead to poor clarified juice (CJ) quality.
      Studies of different liming techniques have been conducted to identify which
      liming technique gives the best clarification performance from juice expressed
      from green cane containing half of all trash extracted (GE). Results have shown
      that lime saccharate addition to juice at 76  degrees C either continuous or
      batchwise gives satisfactory settling rates of calcium phosphate flocs (50-70
      cm/min) and CJ with low turbidity and minimal amounts of mineral constituents.
      Surprisingly, the addition of phosphoric acid (<= 300 mg/kg as P2O5), prior to
      liming to reduce juice turbidity (<= 80%), increased the Mg (<= 101%) and Si (<=
      148%) contents particularly for clarified GE juices. The increase was not
      proportional with increasing phosphoric acid dose. The nature of the flocs
      formed, including the zeta potential of the particles by the different liming
      techniques, has been used to account for the differences in clarification
      performance. Differences between the qualities of the CJ obtained with GE juice
      and that of burnt cane juices with all trash extracted (BE) have been discussed
      to provide further insights into GE processing.

PMID- 22364595
TI  - Association of blepharitis with Demodex: a meta-analysis.
AB  - PURPOSE: To conduct a meta-analysis to confirm the association between Demodex
      infestation and blepharitis. METHODS: We conducted a comprehensive and
      quantitative analysis of relevant published case-control studies which were found
      from the ISI Web of Knowledge, MEDLINE and CNKI from January 1950 to December
      2010. Meta-analysis was applied for 13 of these and included matched data sets,
      using odds ratio (OR) as the effect indicator. Sensitivity was assessed. RESULTS:
      Eleven articles (13 matched data sets) covering four different countries and
      reporting 4741 participants (2098 blepharitis and 2643 controls) were eligible.
      The pooled OR in random effect models was 4.89 (95% confidence interval, 3.00
      7.97). Sensitivity analysis showed that results of pooled ORs in different effect
      models, language, sample size, and control groups were completely consistent,
      which demonstrated a stable association between Demodex infestation and
      blepharitis by meta-analysis. CONCLUSIONS: The association between Demodex
      infestation and blepharitis was statistically significant. The conclusion implies
      that when conventional treatments for blepharitis fail, examination of Demodex
      mites and acaricidal therapy should be considered.

PMID- 22364592
TI  - Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic
      study.
AB  - INTRODUCTION: The aim of this study was to explore the presence and localization
      of myocardial citrullination in samples from rheumatoid arthritis (RA) patients
      compared to rheumatic and non-rheumatic disease control groups. METHODS: Archived
      myocardial samples obtained during autopsy from 1995 to 2009 were assembled into
      four groups: RA; scleroderma; fatal myocarditis; and non-rheumatic disease
      controls. Samples were examined by immunohistochemistry (IHC) for the presence
      and localization of citrullination and peptidyl arginine deiminase enzymes (PADs)
      by a single cardiovascular pathologist blinded to disease group and clinical
      characteristics. RESULTS: Myocardial samples from seventeen RA patients were
      compared with those from fourteen controls, five fatal myocarditis patients, and
      ten scleroderma patients. Strong citrullination staining was detected exclusively
      in the myocardial interstitium in each of the groups. However, average and peak
      anti-citrulline staining was 59% and 44% higher, respectively, for the RA group
      compared to the combined non-RA groups (P < 0.05 for both comparisons).
      Myocardial fibrosis did not differ between the groups. In contrast to
      citrullination, PADs 1 to 3 and 6 were detected in cardiomyocytes (primarily PADs
      1 and 3), resident inflammatory cells (primarily PADs 2 and 4), and, to a smaller
      extent, in endothelial cells and vascular smooth muscle cells. PAD staining did
      not co-localize with anti-citrulline staining in the interstitium and did not
      vary by disease state. CONCLUSIONS: Staining for citrullination was higher in the
      myocardial interstitium of RA compared to other disease states, a finding that
      could link autoimmunity to the known increase in myocardial dysfunction and heart
      failure in RA.

PMID- 22364596
TI  - Prognostic value of diffusion tensor imaging parameters in severe traumatic brain
      injury.
AB  - Diffusion tensor imaging (DTI) has recently emerged as a useful tool for
      assessing traumatic brain injury (TBI). In this study, the prognostic value of
      the relationship between DTI measures and the clinical status of severe TBI
      patients, both at the time of magnetic resonance imaging (MRI), and their
      discharge to acute TBI rehabilitation, was assessed. Patients (n=59) admitted to
      the trauma center with severe closed head injuries were retrospectively evaluated
      after approval from the institution's institutional review board, to determine
      the prognostic value of DTI measures. The relationship of DTI measures, including
      apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial
      (lambda||) and radial diffusivity (lambda?) from the whole brain white matter,
      internal capsule, genu, splenium, and body of the corpus callosum, were compared
      with neurological status at MRI and at discharge to acute TBI rehabilitation.
      Whole brain white matter averages of ADC, lambda||, and lambda?, and their
      coefficient of variation (CV) were significantly correlated with the Glasgow Coma
      Scale (GCS) score on the day of MRI. The average lambda|| was significantly
      correlated with GCS scores on the day of MRI in all measured brain regions.
      Outcomes were associated with whole brain white matter averages of ADC and
      lambda||, and the CVs of FA, ADC, lambda||, and lambda?; and the averages and CVs
      of FA and lambda|| in all corpus callosum regions. The inclusion of regional and
      global DTI measures improved the accuracy of prognostic models, when adjusted for
      admission GCS score and age (p<0.05). Whole brain white matter and regional DTI
      measures are sensitive markers of TBI, and correlate with neurological status
      both at MRI and discharge to rehabilitation. The addition of DTI measures
      adjusted for age, gender, and admission GCS score significantly improved
      prognostic models.

PMID- 22364597
TI  - Effect of azithromycin on small bowel motility in patients with gastrointestinal
      dysmotility.
AB  - OBJECTIVE: To investigate the effect of azithromycin (AZI) on small bowel
      activity in patients with gastrointestinal dysmotility (GID). MATERIAL AND
      METHODS: Manometric data on a consecutive series of 21 patients was reviewed.
      Only those patients with gastroparesis and small bowel dysmotility as defined by
      antroduodenal manometric criteria were included. Pressure profiles were recorded
      in three stages: baseline period, fed state and postprandial after administration
      of erythromycin (ERY) and AZI. The measured parameters included the number and
      characteristics of activity fronts and migrating motor complexes (MMCs) including
      duration, amplitude and frequency of contractions. The data were analyzed using
      repeated measures analysis of variance for comparison of each medication.
      RESULTS: AZI induced more MMCs in the duodenum with origin of activity fronts in
      the antrum than did ERY (18 patients with AZI, 10 patients with ERY). No
      significant difference between AZI and ERY was seen with respect to the amplitude
      of MMCs or number of cycles per minute. The average duration of activity fronts
      was longer with AZI compared with ERY (AZI mean 18.5 min, ERY mean 9.7 min, p <
      0.02). CONCLUSIONS: AZI induces activity fronts in the antrum followed by
      duodenal contractions more frequently than ERY in patients with GID. AZI
      potentially promises to be a prokinetic for treatment of small bowel dysmotility.

PMID- 22364598
TI  - IL1A-889 C/T gene polymorphism in irritant contact dermatitis.
AB  - BACKGROUND: Upon skin contact to irritants, interleukin-1 alpha (IL-1alpha) is
      released in the stratum corneum as a primary step of skin inflammation.
      Variations in the IL-1A gene have been shown to alter the expression of IL
      1alpha. This may influence the susceptibility to skin inflammation and the
      development of irritant contact dermatitis (ICD). OBJECTIVE: To determine effects
      of an IL1A-889 C/T polymorphism in view of susceptibility to develop irritant
      contact dermatitis. METHODS: In a case-control study, 478 Caucasian patients with
      occupational ICD of the hands were genotyped for an IL1A-889 C/T polymorphism.
      Results were compared to 393 apprentices from the same high risk occupations
      (controls). RESULTS: Trends of a protective effect of the C -> T transition at
      position IL1A-889 were seen (OR = 0.81; 95% CI: 0.65-1.00). The genotype
      distribution for IL1A-889 was 52.2% wild type (C/C), 39.2% heterozygous (C/T) and
      8.6% homozygous for variant allele (T/T) in patients and 46.0%, 42.7% and 11.4%
      in controls. Subgroup analysis, which took into account atopy status and
      exposure, did not reveal a significant effect of this polymorphism for an
      aberrant risk to acquire for ICD. CONCLUSION: Our study indicates a possible
      protective effect of the IL1A-889 C/T polymorphism regarding the development of
      ICD.

PMID- 22364599
TI  - Cellular and physiological mechanisms of new-onset diabetes mellitus after solid
      organ transplantation.
AB  - New-onset diabetes after transplantation is recognized as one of the metabolic
      consequences which may increase the risk of morbidity and mortality after solid
      organ transplantation. The pathophysiology of new-onset diabetes after
      transplantation has not been clearly defined and may resemble that of Type 2
      diabetes, characterized by predominantly insulin resistance or defective insulin
      secretion, or both. This review aims to summarize the current state of knowledge
      regarding the prevalence, consequences, pathogenesis, and management of new-onset
      diabetes after transplantation, with a major focus on the possible mechanisms
      involved in the pathogenesis of the disorder. The aetiology of new-onset diabetes
      after transplantation is multifactorial, with diabetogenic immunosuppressive
      drugs playing a major role. Multiple cellular and physiologic mechanisms are
      involved in the process. Selection of an appropriate maintenance
      immunosuppressive regimen should involve balancing the risk of patient and graft
      survival vs. the potential for new-onset diabetes after transplantation.

PMID- 22364600
TI  - Dietary fish oil regulates gene expression of cholesterol and bile acid
      transporters in mice.
AB  - AIM:   Fish oil rich in n-3 polyunsaturated fatty acids is known to affect
      hepatic lipid metabolism. Several studies have demonstrated that fish oil may
      affect the bile acid metabolism as well as lipid metabolism, whereas only scarce
      data are available. The aim of this study was to investigate the effect of fish
      oil on the gene expression of the transporters and enzymes related to bile acid
      as well as lipid metabolism in the liver and small intestine. METHODS:   Seven
      week old male C57BL/6 mice were fed diets enriched in 10% soybean oil or 10% fish
      oil for 4 weeks. After 4 weeks, blood, liver and small intestine were obtained.
      RESULTS:   Hepatic mRNA expression of lipids (Abcg5/8, multidrug resistance gene
      product 2) and bile acids transporters (bile salt export pump, multidrug
      resistance associated protein 2 and 3, organic solute transporter alpha) was
      induced in fish oil-fed mice. Hepatic Cyp8b1, Cyp27a1 and bile acid CoA : amino
      acid N-acyltransferase were increased in fish oil-fed mice compared with soybean
      oil fed mice. Besides, intestinal cholesterol (Abcg5/8) and bile acid
      transporters (multidrug resistance associated protein 2 and organic solute
      transporter alpha) were induced in fish oil-fed mice. CONCLUSION:   Fish oil
      induced the expression of cholesterol and bile acid transporters not only in
      liver but in intestine. The upregulation of Abcg5/g8 by fish oil is caused by an
      increase in cellular 27-HOC through Cyp27a1 induction. The hepatic induction of
      bile acid synthesis through Cyp27a1 may upregulate expression of bile acid
      transporters in both organs.

PMID- 22364601
TI  - Paternal isodisomy of chromosome 2 in a child with bile salt export pump
      deficiency.
AB  - We describe a child with progressive familial intrahepatic cholestasis (PFIC) of
      type 2 inherited as uniparental isodisomy of chromosome 2. Bile salt export pump
      (BSEP) deficiency is a severe, genetically determined subtype PFIC caused by
      mutations in ABCB11, the gene encoding a bile salt transporter protein. Clinical
      and pathological diagnosis in PFIC2 is corroborated by an ample array of ABCB11
      mutations, inherited in an autosomal recessive fashion. We report clinical,
      pathological, and molecular studies in a child with PFIC2. A 5.5-year-old boy
      harbored a described pathogenic mutation (p.R832C) in ABCB11. The mutation was
      found to be homozygous in the patient and heterozygous in DNA from paternal, but
      not maternal blood. Having ruled out maternal gene deletion and somatic
      mosaicism, we showed that the child had inherited an isodisomic paternal
      chromosome 2, including the 2q31.1 region where ABCB11 is located. The present
      report is the first description of uniparental isodisomy in a hepatic heritable
      disorder. Recognizing isodisomic transmission may have a significant impact on
      genetic counseling helping to define the risk of recurrence in subsequent
      pregnancies.

PMID- 22364603
TI  - [Integrated approach to comorbidity in patients with psoriasis.Working Group on
      Psoriasis-associated Comorbidities].
AB  - The relationship between psoriasis and associated diseases has drawn particular
      interest in recent years. To provide appropriate management of psoriasis from an
      early stage, it is necessary to include prompt diagnosis of concomitant disease
      and to prevent and treat any comorbidity found. Such an integrated approach also
      serves to ensure that the drugs used to treat associated diseases do not
      interfere with the management of psoriasis, and vice versa. This clinical
      practice guideline on the management of comorbidity in psoriasis has been drawn
      up to help dermatologists to achieve an integrated approach to this inflammatory
      disease. The guide focuses primarily on the diseases most often found in patients
      with psoriasis, which include psoriatic arthritis, cardiovascular disease,
      nonalcoholic fatty liver disease, inflammatory bowel disease, lymphoma, skin
      cancer, anxiety, and depression. Cardiovascular disease is approached through the
      study of its major risk factors (obesity, diabetes mellitus, hypertension,
      dyslipidemia, and metabolic syndrome). Other cardiovascular risk factors related
      to lifestyle, such as smoking and alcohol consumption, are also discussed. The
      overall aim of this guide is to provide the dermatologist with a precise, easy to
      use tool for systematizing the diagnosis of comorbidity in these patients and to
      facilitate decisions regarding referral and treatment once associated diseases
      have been found. The specific objectives are as follows: a) to review the most
      common diseases associated with psoriasis, including the prevalence of each one
      and its importance to the dermatologist; b) to provide guidelines for the
      physical examination, diagnostic tests, and clinical criteria on which to base a
      preliminary diagnosis; c) to establish criteria for the appropriate referral of
      patients with suspected comorbidity; d) to provide information on how therapies
      for psoriasis may modify the course of associated diseases, and e) to provide
      information concerning treatments prescribed for associated diseases that may
      have an impact on the course of psoriasis. This guide has been written by a
      working group of guideline methodologists and clinical experts. The selection of
      the diseases included was based on a systematic review of the literature and a
      summary of available evidence; information on the prevalence of each comorbidity
      was also taken from the literature. The recommendations on diagnostic criteria
      are based on the main clinical practice guidelines for each of the diseases
      discussed and on the recommendations of the expert advisory group. The
      information regarding the repercussions of psoriasis treatments on comorbid
      diseases was obtained from the summary of product characteristics of each drug.
      The statements concerning the impact on psoriasis of the associated diseases and
      their treatment are based on the review of the literature.

PMID- 22364604
TI  - Meta-analysis of randomized trials comparing antibiotic therapy with appendectomy
      for acute uncomplicated (no abscess or phlegmon) appendicitis.
AB  - BACKGROUND: The objective was to conduct a meta-analysis of randomized controlled
      trials evaluating the efficacy and morbidity of the management of acute
      uncomplicated (no abscess or phlegmon) appendicitis by antibiotics versus
      appendectomy. METHODS: Appropriate trials were identified. The seven outcome
      variables were overall complication rate, treatment failure rate for index
      hospital admission, overall treatment failure rate, length of stay (LOS),
      utilization of pain medication, duration of pain, and sick leave. Both fixed and
      random effects meta-analyses were performed using odds ratios (ORs) and weighted
      or standardized mean differences (WMDs or SMDs, respectively). RESULTS: Five
      trials totaling 980 patients (antibiotics=510, appendectomy=470) were analyzed.
      In three of the seven outcome analyses, the summary point estimates favored
      antibiotics over appendectomy, with a 46% reduction in the relative odds of
      complications (OR 0.54; 95% confidence interval [CI] 0.37, 0.78; p=0.001); a
      reduction in sick leave/disability (SMD -0.19; CI -0.33, -0.06; p=0.005), and
      decreased pain medication utilization (SMD -1.55; CI -1.96, -1.14; p<0.0001). For
      overall treatment failure, the summary point estimate favored appendectomy, with
      a 40.2% failure rate for antibiotics versus 8.5% for appendectomy (OR 6.72; CI
      0.08, 12.99; p<0.001). Initial treatment failure, LOS, and pain duration were
      similar in the two groups. CONCLUSIONS: Non-operative management of uncomplicated
      appendicitis with antibiotics was associated with significantly fewer
      complications, better pain control, and shorter sick leave, but overall had
      inferior efficacy because of the high rate of recurrence in comparison with
      appendectomy.

PMID- 22364605
TI  - Bladder pressure measurements and urinary tract infection in trauma patients.
AB  - BACKGROUND: The purpose of this trial was to determine if using a closed
      technique for bladder pressure measurements (BPMs) would eliminate them as a risk
      factor for urinary tract infection (UTI) in trauma patients, as was shown
      previously using an open technique. METHODS: Data were collected prospectively
      from January 2006 until December 2009 by a dedicated epidemiology nurse and
      combined with trauma registry data at our Level 1 trauma center. All trauma
      patients admitted to the surgical trauma intensive care unit (STICU) with and
      without UTIs were compared for demographic and epidemiologic data. A closed
      system was used in which the urinary drainage catheter (UDC) remained connected
      to the bag and 45 mL of saline was injected through a two-way valved sideport,
      with subsequent measurements through the sideport. RESULTS: There were 1,641
      patients in the trial. The UTI group was sicker (Injury Severity Score [ISS]
      18.7+/-11.9 no UTI vs. 28+/-10.7 UTI; p<0.0001), with longer stays (11.4+/-12.4
      days no UTI vs. 37.9+/-20.3 days UTI; p<0.0001) and more UDC days (4.3+/-6.6 no
      UTI vs. 23.9+/-16.6 UTI; p<0.0001). The BPM group had more UDC days (15.6 days+/
      16.0 BPM vs. 5.4 days+/-7.3 no BPM; p<0.0001), yet no difference in UTI
      rate/1,000 UDC days (5.7 no BPM vs. 8.0 BPM; p=0.5291). Logistic regression
      demonstrated only UDC days to be a predictor of UTI (1.125; 95% confidence
      interval [CI] 1.097-1.154; p<0.0001), whereas ISS (1.083, 95% CI 1.063-1.104;
      p<0.0001) and age (1.051, 95% CI 1.037-1.065; p<0.0001) were the only predictors
      of death. CONCLUSION: Although patients undergoing BPM have more UTIs than
      patients without BPM, the measurements are not an independent predictor of UTI
      when done by the closed technique. These findings emphasize the judicious use of
      BPM with a closed system and, more importantly, the need for early removal of
      catheters.

PMID- 22364602
TI  - Therapeutic implications of disorders of cell death signalling: membranes, micro
      environment, and eicosanoid and docosanoid metabolism.
AB  - Disruptions of cell death signalling occur in pathological processes, such as
      cancer and degenerative disease. Increased knowledge of cell death signalling has
      opened new areas of therapeutic research, and identifying key mediators of cell
      death has become increasingly important. Early triggering events in cell death
      may provide potential therapeutic targets, whereas agents affecting later signals
      may be more palliative in nature. A group of primary mediators are derivatives of
      the highly unsaturated fatty acids (HUFAs), particularly oxygenated metabolites
      such as prostaglandins. HUFAs, esterified in cell membranes, act as critical
      signalling molecules in many pathological processes. Currently, agents affecting
      HUFA metabolism are widely prescribed in diseases involving disordered cell death
      signalling. However, partly due to rapid metabolism, their role in cell death
      signalling pathways is poorly characterized. Recently, HUFA-derived mediators,
      the resolvins/protectins and endocannabinoids, have added opportunities to target
      selective signals and pathways. This review will focus on the control of cell
      death by HUFA, eicosanoid (C20 fatty acid metabolites) and docosanoid (C22
      metabolites), HUFA-derived lipid mediators, signalling elements in the micro
      environment and their potential therapeutic applications. Further therapeutic
      approaches will involve cell and molecular biology, the multiple hit theory of
      disease progression and analysis of system plasticity. Advances in the cell
      biology of eicosanoid and docosanoid metabolism, together with structure/function
      analysis of HUFA-derived mediators, will be useful in developing therapeutic
      agents in pathologies characterized by alterations in cell death signalling.

PMID- 22364606
TI  - Depressive symptoms as a predictor of quality of life in cerebral small vessel
      disease, acting independently of disability; a study in both sporadic small
      vessel disease and CADASIL.
AB  - BACKGROUND: Cerebral small vessel disease causes lacunar stroke, and more
      recently has been implicated as a cause of depression. Factors causing reduced
      quality of life in small vessel disease, including the relative contributions of
      disability and depressive symptoms, remain uncertain. METHODS: One hundred
      patients with small vessel disease and 55 controls completed the Stroke-Specific
      Quality of Life scale. The protocol was repeated in 40 patients with the young
      onset genetic form of small vessel disease, cerebral autosomal dominant
      arteriopathy with sub-cortical infarcts and leukoencephalopathy, and 35 controls.
      Disability, activities of daily living, cognition and depression were measured.
      RESULTS: Quality of life was significantly lower in small vessel disease versus
      controls: mean (standard deviation), 196?8 (35?2) vs. 226?8 (15?3), P < ?0001.
      Depressive symptoms were the major predictor of quality of life, explaining 52?9%
      of variance. The only other independent predictor was disability, explaining an
      additional 18?4%. A similar pattern was found in the young-onset genetic group,
      with reduced quality of life 202?0 (29?7) vs. controls 228?6 (13?1) P < ?0001,
      and depressive symptoms accounting for 42?2% of variance. Disability explained an
      additional 17?6%. Relationships between depression and quality of life, and
      disability and quality of life were independent of one another. CONCLUSIONS:
      Depressive symptoms, often unrecognized, are a major determinant of reduced
      quality of life in small vessel disease. They account for greater reduction than,
      and are independent of, disability. This relationship may reflect the proposed
      causal association between white matter disease and depression. Treatment of
      depressive symptoms might significantly improve quality of life in small vessel
      disease.

PMID- 22364607
TI  - Quality of life in patients operated on for digestive neoplasia: a prospective
      study.
AB  - AIM: The aim of this study was to evaluate the quality of life in patients having
      surgery for a digestive neoplasm and to monitor how the patient's perception
      evolves during the first 6 months after surgery. METHOD: A prospective study was
      carried out on the pre and postoperative quality of life of patients undergoing
      surgery for a digestive system neoplasm between May 2009 and December 2010.
      Patients were asked to complete the Short Form (36) Health Survey questionnaire
      (SF-36; spanish version 1.4). RESULTS: The study included 80 patients. At 1 month
      after surgery there was a statistically significant improvement in some domains
      of the SF-36. At 6 months, a statistically significant improvement was seen in
      physical functioning, social functioning, mental health and in the two physical
      and mental domains. We also found statistically significant differences, with
      women having a worse quality of life. CONCLUSION: Comparison of quality of life
      before and 6 months after surgical intervention showed improvement in both the
      psychological and the physical elements. This can be attributed to the fact that
      the patients have had time to recover from the surgery.

PMID- 22364608
TI  - How chain plasmons govern the optical response in strongly interacting self
      assembled metallic clusters of nanoparticles.
AB  - Self-assembled clusters of metallic nanoparticles separated by nanometric gaps
      generate strong plasmonic modes that support both intense and localized near
      fields. These find use in many ultrasensitive chemical and biological sensing
      applications through surface enhanced Raman scattering (SERS). The inability to
      control at the nanoscale the structure of the clusters on which the optical
      response crucially depends, has led to the development of general descriptions to
      model the various morphologies fabricated. Here, we use rigorous electrodynamic
      calculations to study clusters formed by a hundred nanospheres that are separated
      by ~1 nm distance, set by the dimensions of the macrocyclic molecular linker
      employed experimentally. Three-dimensional (3D) cluster structures of moderate
      compactness are of special interest since they resemble self-assembled clusters
      grown under typical diffusion-limited aggregation conditions. We find very good
      agreement between the simulated and measured far-field extinction spectra,
      supporting the equivalence of the assumed and experimental morphologies. From
      these results we argue that the main features of the optical response of two- and
      three-dimensional clusters can be understood in terms of the excitation of simple
      units composed of different length resonant chains. Notably, we observe a
      qualitative difference between short- and long-chain modes in both spectral
      response and spatial distribution: dimer and short-chain modes are observed in
      the periphery of the cluster at higher energies, whereas inside the structure
      longer chain excitation occurs at lower energies. We study in detail different
      configurations of isolated one-dimensional chains as prototypical building blocks
      for large clusters, showing that the optical response of the chains is robust to
      disorder. This study provides an intuitive understanding of the behavior of very
      complex aggregates and may be generalized to other types of aggregates and
      systems formed by large numbers of strongly interacting particles.

PMID- 22364609
TI  - Proteomics-based strategy to delineate the molecular mechanisms of RhoGDI2
      induced metastasis and drug resistance in gastric cancer.
AB  - Rho GDP dissociation inhibitor 2 (RhoGDI2) was initially identified as a
      regulator of the Rho family of GTPases. Our recent works suggest that RhoGDI2
      promotes tumor growth and malignant progression, as well as enhances
      chemoresistance in gastric cancer. Here, we delineate the mechanism by which
      RhoGDI2 promotes gastric cancer cell invasion and chemoresistance using two
      dimensional gel electrophoresis (2-DE) on proteins derived from a RhoGDI2
      overexpressing SNU-484 human gastric cancer cell line and control cells.
      Differentially expressed proteins were identified using matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). In total,
      47 differential protein spots were identified; 33 were upregulated, and 14 were
      downregulated by RhoGDI2 overexpression. Upregulation of SAE1, Cathepsin D,
      Cofilin1, CIAPIN1, and PAK2 proteins was validated by Western blot analysis. Loss
      of-function analysis using small interference RNA (siRNA) directed against
      candidate genes reveals the need for CIAPIN1 and PAK2 in RhoGDI2-induced cancer
      cell invasion and Cathepsin D and PAK2 in RhoGDI2-mediated chemoresistance in
      gastric cancer cells. These data extend our understanding of the genes that act
      downstream of RhoGDI2 during the progression of gastric cancer and the
      acquisition of chemoresistance.

PMID- 22364610
TI  - Long-term, longitudinal follow-up of individuals with unilateral cleft lip and
      palate after the Gothenburg primary early veloplasty and delayed hard palate
      closure protocol: speech outcome.
AB  - OBJECTIVE: To investigate long-term, longitudinal speech outcome in patients born
      with unilateral cleft lip and palate treated according to a two-stage primary
      palatal protocol with early veloplasty and delayed hard palate closure. DESIGN:
      Retrospective, longitudinal cohort study. Setting : A university hospital in
      western Sweden. SUBJECTS: A consecutive series of 55 patients from the total
      cohort of 65 were included. All patients had surgical procedures at Sahlgrenska
      University Hospital, Gothenburg, Sweden. METHODS: Standardized audio recordings
      were blindly analyzed at 5, 7, 16, and 19 years of age and after at a clinical
      visit at 10 years of age. Typical cleft speech variables were rated independently
      on ordinal scales. Intelligibility and perceived velopharyngeal function were
      assessed also. Prevalences of speech characteristics were determined, and
      interrater and intrarater agreement were calculated. Results : Prominent
      hypernasality, nasal air leakage, and retracted oral articulation at 5 years were
      markedly reduced throughout the years with low prevalences at ages 16 and 19
      years. Perceived velopharyngeal competence was noted in 82% at age 16 and 87% at
      age 19 years along with normal intelligibility. Pharyngeal flap surgery was
      performed in 6 of the 55 patients (11%). CONCLUSIONS: Long-term speech outcome in
      patients with two-stage palatoplasty with early soft palate repair was considered
      good and improved even before hard palate repair. The typical retracted oral
      articulation was quite frequent during the early ages; whereas, nonoral
      misarticulations were almost nonexistent, implying good velopharyngeal
      competence.

PMID- 22364614
TI  - Current applications of 19F NMR to studies of protein structure and dynamics.

PMID- 22364613
TI  - Existence of the rdl mutant alleles among the anopheles malaria vector in
      Indonesia.
AB  - BACKGROUND: The gamma-aminobutyric acid (GABA) receptor-chloride channel complex
      is known to be the target site of dieldrin, a cyclodiene insecticide. GABA
      receptors, with a naturally occurring amino acid substitution, A302S/G in the
      putative ion-channel lining region, confer resistance to cyclodiene insecticides
      that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan.
      METHODS: A total of 154 mosquito samples from 10 provinces of malaria-endemic
      areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central
      Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North
      Molucca) were obtained and identified by species, using morphological
      characteristic. The DNA was individually extracted using chelex-ion exchanger and
      the DNA obtained was used for analyses using sequencing method. RESULTS:
      Molecular analysis indicated 11% of the total 154 Anopheles samples examined,
      carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl
      302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West
      Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris
      (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and
      Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was
      only found in Anopheles farauti from Molucca. CONCLUSION: The existence of the
      Rdl mutant allele indicates that, either insecticide pressure on the Anopheles
      population in these areas might still be ongoing (though not directly associated
      with the malaria control programme) or that the mutant form of the Rdl allele is
      relatively stable in the absence of insecticide. Nonetheless, the finding
      suggests that integrated pest management is warranted in malaria-endemic areas
      where insecticides are widely used for other purposes.

PMID- 22364615
TI  - Numerical estimation of relaxation and diffusion distributions in two dimensions.

PMID- 22364616
TI  - Metabolic signatures of cancer unveiled by NMR spectroscopy of human biofluids.

PMID- 22364617
TI  - Information for parents and teachers on the European Academy for Childhood
      Disability (EACD) recommendations on developmental coordination disorder.

PMID- 22364618
TI  - Effect of comorbidity on the risk of death associated with antipsychotic use
      among community-dwelling older adults.
AB  - BACKGROUND: Antipsychotics are associated with adverse events and mortality among
      older adults with dementia. The objective of this study was to evaluate the risk
      of death associated with antipsychotic use among community-dwelling older adults
      with a range of comorbidities. METHODS: This was a population-based cohort study
      of all 2,224 residents of Leppavirta, Finland, aged >=65 years on 1 January 2000.
      Records of all reimbursed drug purchases were extracted from the Finnish National
      Prescription Register and diagnostic data were obtained from the Special
      Reimbursement Register. All-cause mortality was evaluated over a nine-year follow
      up period. Time-dependent Cox proportional hazard models were used to compute
      unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of
      mortality of antipsychotic use compared to non-use. RESULTS: In total, 332
      residents used antipsychotics between 2000 and 2008. The unadjusted HR for risk
      of death associated with antipsychotic use was 2.71 (95% CI = 2.3-3.2). After
      adjusting for baseline age, sex, antidepressant use, and diagnostic confounders,
      the HR was 2.07 (95% CI = 1.73-2.47). The adjusted HR was the highest among
      antipsychotic users with baseline respiratory disease (HR = 2.21, 95% CI = 1.30
      3.76). CONCLUSIONS: The increased risk of death associated with antipsychotic use
      was similar across diagnostic categories, the highest being among those with
      baseline respiratory disease. However, the results should be interpreted with
      caution, as the overall sample size of antipsychotic users was small. As in other
      observational studies, residual confounding may account for the higher mortality
      observed among antipsychotic users. Further research is needed to confirm these
      findings.

PMID- 22364619
TI  - Conformation of 2,2,2-trifluoroethanol and the solvation structure of its 2
      fluoropyridine clusters.
AB  - The conformation of 2,2,2-trifluoroethanol (TFE) in the 2-fluoropyridine-(TFE)(m)
      (H(2)O)(n) clusters in a supersonic jet has been investigated with fluorescence
      detected infrared spectroscopy and quantum chemical calculations. It is common to
      the observed clusters that they form chain structures containing the weak
      interaction of the pyridyl CH with the fluorine or oxygen atom in the terminal
      TFE. The detectable conformation of TFE is gauche only even in the case of the
      existence of the strong base such as 2-fluoropyridine. This result is explained
      by the change in hyperconjugation among several dominant orbitals. The preference
      of the terminal TFE in the mixed clusters with TFE and water solvents is
      observed, which is ascribed to the stronger cooperative effect of TFE than water.

PMID- 22364621
TI  - Dihydrogen complexes of iridium and rhodium.
AB  - A series of iridium and rhodium pincer complexes have been synthesized and
      characterized: [(POCOP)Ir(H)(H(2))] [BAr(f)(4)] (1-H(3)), (POCOP)Rh(H(2)) (2
      H(2)), [(PONOP)Ir(C(2)H(4))] [BAr(f)(4)] (3-C(2)H(4)), [(PONOP)Ir(H)(2))]
      [BAr(f)(4)] (3-H(2)), [(PONOP)Rh(C(2)H(4))] [BAr(f)(4)] (4-C(2)H(4)) and
      [(PONOP)Rh(H(2))] [BAr(f)(4)] (4-H(2)) (POCOP = kappa(3)-C(6)H(3)-2,6
      [OP(tBu)(2)](2); PONOP = 2,6-(tBu(2)PO)(2)C(5)H(3)N; BAr(f)(4) = tetrakis(3,5
      trifluoromethylphenyl)borate). The nature of the dihydrogen-metal interaction was
      probed using NMR spectroscopic studies. Complexes 1-H(3), 2-H(2), and 4-H(2)
      retain the H-H bond and are classified as eta(2)-dihydrogen adducts. In contrast,
      complex 3-H(2) is best described as a classical dihydride system. The presence of
      bound dihydrogen was determined using both T(1) and (1)J(HD) coupling values:
      T(1) = 14 ms, (1)J(HD) = 33 Hz for the dihydrogen ligand in 1-H(3), T(1)(min) =
      23 ms, (1)J(HD) = 32 Hz for 2-H(2), T(1)(min) = 873 ms for 3-H(2), T(1)(min) = 33
      ms, (1)J(HD) = 30.1 Hz for 4-H(2).

PMID- 22364620
TI  - Effects of hypothermia on cerebral autoregulatory vascular responses in two
      rodent models of traumatic brain injury.
AB  - Traumatic brain injury (TBI) can trigger disturbances of cerebral pressure
      autoregulation that can translate into the generation of secondary insults and
      increased morbidity/mortality. Few therapies have been developed to attenuate the
      damaging consequences of disturbed autoregulatory control, although some suggest
      that hypothermia may exert such protection. Here we reexamine this issue of
      traumatically induced autoregulatory disturbances and their modulation by
      hypothermic intervention, examining these phenomena in two different models of
      TBI. Adult rats were subjected to either impact acceleration injury (IAI) or
      lateral fluid percussion injury (LFPI) followed by the insertion of cranial
      windows to assess the pial arteriolar cerebral autoregulatory vascular response
      to the post-traumatic induction of sequential reductions of arterial blood
      pressure. The potential for continued pial vasodilation in response to declining
      blood pressure was directly measured post-injury and compared with that in
      injured groups subjected to 33 degrees  C of hypothermia of 1-2 h duration
      initiated 1 h post-injury. We observed that the TBI resulted in either impaired
      or abolished cerebral vascular dilation in response to the sequential declines in
      blood pressure. Following IAI there was a 50% reduction in the vasculature's
      ability to dilate in response to the induced hypotension. In contrast, following
      LFPI, the vascular response to hypotension was abolished both ipsilateral and
      contralateral to the LFPI. In animals sustaining IAI, the use of 1 h post
      traumatic hypothermia preserved vascular dilation in response to declines in
      blood pressure in contrast to the LFPI in which the use of the same strategy
      afforded no improvement. However, with LFPI, the use of 2 h of hypothermia
      provided partial vascular protection. These results clearly illustrate that TBI
      can alter the cerebral autoregulatory vascular response to sequentially induced
      hypotensive insult, whereas the use of post-traumatic hypothermia provides
      benefit. Collectively, these studies also demonstrate that different animal
      models of TBI can evoke different biological responses to injury.

PMID- 22364622
TI  - Comitant horizontal strabismus in South African black and mixed race children--a
      clinic-based study.
AB  - PURPOSE: To examine the types of comitant horizontal strabismus in children
      belonging to the two largest ethnic groups of the Western Cape, South Africa.
      METHODS: Retrospective review of 2371 children presenting with comitant
      horizontal strabismus to a single, large, pediatric tertiary referral center in
      Cape Town, South Africa, between 1997 and 2007. RESULTS: 81% of children were of
      mixed race and 19% were black. The overall esotropia:exotropia ratio was 73:27.
      For black children this was 85:15 and for mixed race, 71:29. The overwhelming
      majority of black children had congenital esotropias (74%), whereas accommodative
      esotropia was rare (9%). In mixed race children, esotopias were more equally
      divided between congenital (46%) and accommodative types (35%). Exotropias were
      uncommon in black children, and were mainly constant (61%). Intermittent
      exotropias predominated in mixed race children (55%). CONCLUSION: Congenital
      esotropia remains common in South African black children, and of the few who
      presented with exotropia, most had constant type. Accommodative esotropias were
      more prevalent in South African mixed race children, but in smaller proportions
      than in other studies. Exotropias were mostly intermittent in this ethnic group,
      and showed a similar profile to that in white American children.

PMID- 22364623
TI  - [Chemotherapy in perioperative setting for infiltrative bladder cancer].
AB  - INTRODUCTION: Despite an aggressive initial treatment, only 60% of patients with
      T2-staged bladder tumours, 50% with T3a and 15% with T3b staged-tumours will be
      alive at 5 years. The purpose of this review is to clarify the potential role of
      chemotherapy in localised urothelial tumours, which has not been clearly defined.
      MATERIALS AND METHODS: To address this question, we reviewed published randomized
      trials of chemotherapy in urothelial tumours of the bladder in both neoadjuvant
      and adjuvant settings from 1980 and 2010 and corresponding meta-analyses in
      PubMed. RESULTS: In the neoadjuvant setting, a meta-analysis of individual data
      from 3005 patients demonstrated an absolute survival benefit of 5.5% at 5 years.
      Despite these results, neoadjuvant chemotherapy is very rarely proposed in this
      indication. Comparative trials performed in the adjuvant setting have been
      limited by major methodological weaknesses, preventing definitive conclusions. In
      a meta-analysis based on individual data from 491 patients, a 25% reduction in
      death risk was observed for an absolute gain of 9% at 3 years. CONCLUSION: In
      light of these data, chemotherapy should be offered early and proposed as a
      reasonable option for patients for tumours with extravesical extension or with
      nodal involvement detected postoperatively, neoadjuvant chemotherapy is the
      standard of care.

PMID- 22364624
TI  - [Results obtained after robotic-assisted laparoscopic sacral colpopexy for the
      management of urogenital prolapse: a review].
AB  - INTRODUCTION: Laparoscopic sacral colpopexy (LSCP) is one of the gold standard
      surgical treatment for the management of urogenital prolapse. Robot-assisted
      laparoscopic sacrocolpopexy (RALSCP) is an alternative surgical access which has
      been recently proposed. The aim of the current study was to report the functional
      results obtained after RALSCP. MATERIAL AND METHODS: [corrected] A systematic
      review of the scientific literature was achieved in the Pubmed database, using
      the following keywords: robotic; robot; sacrocolpopexy; sacralcolpopexy. Clinical
      cases and series of less than five cases were spontaneously not selected herein.
      RESULTS: Overall, 12 series in published between September 2004 and September
      2011 which included 350 female patients were selected. The mean age was 63 years
      old with a pelvic organ prolapse of stage 3 to 4 in the Baden Walker
      classification. The mean operative time of the RALSCP was 207 minutes with a
      conversion rate of 3,4% and an intraoperative complication rate of 4,6%. The mean
      length of hospital stay was 3 days and the perioperative complication rate of
      7,1%. The success rate of the RALSCP was 97% and the vaginal erosion rate was
      2,5% with a median follow-up of 13,5 months. CONCLUSION: The mid-term functional
      results obtained after RALSCP were equivalent to those obtained with the LSCP
      approach. However, there is no prospective randomized comparison available
      between the two access so far. In addition, the experience with RALSCP remains
      limited due to the important cost that the robotic access generates.

PMID- 22364625
TI  - [Prone and supine position for percutaneous nephrolithotomy: is it necessary to
      change the operative technique?].
AB  - PURPOSE: To assess the safety and effectiveness of percutaneous nephrolithotomy
      performed in the supine position. To investigate whether the change in operative
      technique, between prone and supine position, is easy. METHOD: Thirty patients
      who underwent percutaneous nephrolithotomy, by one surgeon in one hospital, were
      studied retrospectively. The eight first cases were performed in prone position,
      and the following 22 patients were operated in supine position according to
      Valdivia's operative technique. Data were analyzed with t-test. We considered
      P<0.05 as significant. RESULTS: Surgical complication rate, transfusion rate and
      fever rate were the same for both groups. Success rate was 72% in supine position
      group and 63% in prone position group (P>0.05). These results were comparable
      with the data of the literature. Only operative time was shorter in supine
      position group with significant statistical difference (P=0.02). CONCLUSION: In
      our experience, percutaneous nephrolithotomy in the supine position was safe and
      efficient, and outcomes were similar to that in the prone position. Learning
      curve was easy and fast.

PMID- 22364626
TI  - [Magnetic resonance imaging for delineation of prostate in radiotherapy:
      monocentric experience and review of literature].
AB  - PURPOSE: To assess the benefits of magnetic resonance imaging (MRI) in the
      dosimetric treatment planning for prostate radiotherapy. PATIENTS AND METHODS:
      Ten consecutive patients have been enrolled. They were treated for a low risk
      prostate adenocarcinoma. A rigid superimposition was performed between MRI and
      scan slides obtained at time of virtual simulation, then prostate volume was
      delineated by four to five physicians, on TDM slides and on MRI/TDM
      superimposition. For each treatment plan, we assessed the impact of MRI in terms
      of planned treatment volume (PTV) position, individual variability of prostate
      delineation and doses delivered to the critical organs. The prescribed dose was
      74 Gy in 37 fractions to the PTV. RESULTS: PTV delineated on TDM (V(TDM)) were
      1.15 (SD 3.71) larger than volumes delineated on MRI. Prostate apex was 4.6 mm
      (SD 2.87) lower on TDM than on MRI. Posterior limit of the prostate was in mean 4
      mm more posterior on TDM. The variability between physicians in terms of prostate
      delineation was lower using MRI. For apex, these variations were 6.8 mm using
      TDM, versus 3.3 mm using MRI. Mean rectal dose was 8 % lower with MRI, compared
      to delineation using TDM. CONCLUSION: Superimposition TDM/MRI improves accuracy,
      decreases delineation variability, and allows to spare anterior part of the
      rectum from irradiation. It remains unknown whether this strategy translates into
      clinical benefit.

PMID- 22364627
TI  - [Use of Eductyl((r)) suppository for rectal preparation before prostate biopsy:
      an observational survey].
AB  - BACKGROUND: Local preparation of rectum governs the possibly survenue of
      complications during transrectal ultrasound guided biopsies of prostate.
      OBJECTIVE: To determine the efficacy and acceptability of rectal preparation
      (Eductyl((r)) suppository) in patients undergoing a transrectal prostate biopsy.
      PATIENTS AND METHODS: From May to August 2005, eight urologists (Bel-Air
      Urological Center, Bordeaux) included 137 patients (mean age 66.4 years) with an
      indication of prostate biopsies. All patients were administrated prophylactic
      antibiotic therapy. They used Eductyl((r)) effervescent suppositories for local
      preparation, the day before and/or the morning of the exam. RESULTS: Rectal
      vacuity was satisfactory or very satisfactory for 99% of patients. Introduction
      of probe and tracking of prostate were easy or very easy in 99% of cases. Eight
      days after the exam, only 35% of patients had suffered anal or rectal pain during
      a mean of 2 days. Most of patients recovered bowel function without requiring
      treatment and without any difficulty or pain. The bowel function recovery
      occurred the day of prostate biopsy and the day after for 28.4% and 62.2% of
      patients, respectively. CONCLUSION: Urologists considered that the use of
      Eductyl((r)) suppositories before prostate biopsies ensured a satisfactory rectal
      preparation and optimal conditions for the exam. Moreover, this preparation was
      well accepted by patients.

PMID- 22364628
TI  - [Interest of flexible videocystoscopy in blue light (+Hexvix((r))) in
      consultation for the diagnosis of vesical tumor].
AB  - OBJECTIVES: Estimate the feasibility and the results of the realization in
      consultation of a flexible videocystoscopy in blue light preceded by an
      instillation of Hexvix((r)) (GE Healthcare) for the initial diagnosis or the
      surveillance of vesicals tumors (VT). The objective of this study was to compare
      the number of hurts seen in white light and in blue light, and to estimate in
      which percentage of case the use of the Hexvix((r)) in consultation modified the
      care. PATIENTS AND METHODS: Thirty consecutive patients (26 men and four women)
      were estimated prospectively by vesical videofibroscopy in blue light (Wolf's PD
      videofibroscope) realized 1 hour after an endovesical instillation of
      Hexvix((r)). All the examinations were realized in external consultation under
      local anesthetic by xylocaine gel: 23 (76.6%) patients within the framework of a
      surveillance of VT and seven (23.4%) for the diagnosis of a hematuria with normal
      echography. When a suspect hurt or a VT was discovered, the patients benefited
      from an endoscopic resection under anesthesia with new cystoscopy in blue light.
      RESULTS: Suspect hurts were revealed in 10 out of 30 patients, five in white and
      blue light, five in blue light only. Among the five only visible hurts in blue
      light, three were urothelial tumors (any pTa of bottom-rank, less of 5 mm) and
      two non-specific hurts. No CIS's hurt was revealed during this study. The
      fibroscopy in blue light allowed to diagnose invisible hurts in white light in
      three patients (10%) and has modified the care of five patients (16.7%). The
      duration of the cystoscopy was on average of 9.5 minutes. The tolerance of the
      examination was good and no complication arose. CONCLUSION: The use of the
      flexible videocystoscopy in blue light +Hexvix((r)) has allowed to improve the
      rate of detection of VT. Except CIS's hurts, this improvement was bound to the
      diagnosis of little aggressive small-sized VT. The indications must be specified
      by studies of bigger scale and a medical economic evaluation.

PMID- 22364629
TI  - [Erythropoietin before severe hypospadias repair: fewer complications?].
AB  - OBJECTIVE: To study the effect of a preparation by erythropoietin before Onlay's
      intervention on postoperative hematocrits and medium-term results of the surgery.
      PATIENTS AND METHODS: Twenty-one patients were operated on by Onlay's technique
      between 2001 January and 2008 September, after being treated by erythropoietin.
      Seven had a midshaft hypospadias, two a posterior hypospadias and 12 a
      penoscrotal hypospadias. All children were examinated four months after surgery
      to evaluate the surgical results. RESULTS: After the surgery, 18 children had an
      apical meatus (85.7%). Three had a balanopreputial meatus, two a stenosis of the
      meatus. Two children were reoperated on, one with the Duplay's technique, the
      other for a meatostomy. No fistula, no necrosis of the preputial flap was
      observed. The preoperative hematocrit was measured at 41%, with an increase of
      3.8% because of the preparation. Peroperative blood loss was evaluated at 6.6%.
      After surgery, 12 children had an hematocrit inferior than 35%, four an
      hematocrit inferior than 30%. No transfusion was needed. CONCLUSION: Preparation
      by erythropoietin before severe hypospadias surgery seemed to have several
      advantages: a more elevated hematocrit after surgery than with an iron
      preparation alone, and a lower rate of postoperative complications, including
      fistulas and necrosis of the preputial flap.

PMID- 22364630
TI  - [Analysis of the bibliometrics score of surgical department from the academic
      hospitals of Paris: what is the rank of urology?].
AB  - OBJECTIVES: Analyze the results of the bibliometric system and analysis of
      scientific publications (SIGAPS) in the Assistance publique-Hopitaux de Paris (AP
      HP) and compare the scientific production among the various surgical disciplines
      of the academic hospitals of Paris and define the place of urology. METHODS: The
      publications from 115 surgical departments between 2006 and 2008 were included.
      Only surgical departments were considered in the current study. The following
      data were taken into account: the hospital department of origin, the number of
      articles published, the number of first place, last places, the number of full
      time unit, the SIGAPS score. Statistical analysis focused on the quality and on
      the quantity of published articles per surgeons and per department. There were
      eight academic departments of urology identified within the AP-HP. RESULTS: The
      database contained information for 115 surgical departments. The mean number of
      articles published by department was 42.89+/-27.34 (13.2 to 110.75). The mean
      number of publications per full-time surgeon was 6.7+/-2.59 (3.77 to 12.84), or a
      mean of 2.25+/-0.86 released by full-time and by year. The median score SIGAPS of
      surgery was 304 with a wide interval (122 to 903.5). Urology was the specialty
      with the highest median score compared to other surgical specialties. The
      department, which published the most, was the center 1, in comparison with the
      center 6 which was publishing the most in A/B ranking journals. CONCLUSION:
      Urology was the absolute leader by far in terms of scientific publications in the
      AP-HP when compared to other surgical disciplines. The discipline is organized
      efficiently to juggle clinical work and research indicating a certain dynamism of
      the teams that invest there to fulfill the missions assigned to them in the
      University Hospital and the part of the autonomy of the universities.

PMID- 22364631
TI  - [Congenital mesoblastic nephroma: diagnosis and treatment of one case].
AB  - The congenital mesoblastic nephroma (CMN) described by Bolande et al. in 1967 is
      a renal tumor often discovered in neonatal period and early childhood. It's
      usually considered as a benign tumor with good prognostic for which nephrectomy
      is the reference treatment. But some cases of local recidives and metastatic
      sites had been described in the literature. For these reasons histologic analysis
      and quality of follow up are very important. In this observation we describe a
      neonatal kind of CMN and we discuss this pathology.

PMID- 22364632
TI  - [Distal and late ureteral obstruction: a rare complication following
      dextranomer/hyaluronic acid injection for vesicoureteral reflux in children].
AB  - Surgically relevant obstruction after dextranomer/hyaluronic acid injection
      (Dx/Ha, Deflux((r))) for the treatment of vesicoureteral reflux (VUR) is rare
      with a 0.6% incidence. It occurs usually during the early postoperative period.
      We report here the case of a 9-year-old boy with a history of VUR who was
      previously treated with Deflux((r)) and was referred more than 2 years later with
      acute flank pain (as he already did 2 weeks after surgery with a spontaneous
      relief under medical treatment). Initial radiological investigations showed
      hydronephrosis caused by distal ureteral obstruction which required open surgery
      removal of the Dx/Ha and Cohen procedure. This is the second case of delayed
      symptomatic obstruction due to Dx/Ha reported in the literature.

PMID- 22364633
TI  - [Is SIGAPS score a good evaluation criteria for university departments?].

PMID- 22364634
TI  - From many one: the various approaches to pediatric heart transplantation.

PMID- 22364635
TI  - Treatment of livedoid vasculopathy with alprostadil (PGE-1): case report and
      review of published literature.

PMID- 22364636
TI  - Plasma testosterone is associated with Framingham risk score.
AB  - INTRODUCTION: The Framingham risk score predicts a patient's 10-year risk of
      developing cardiovascular disease. Many risk factors included in its calculation
      influence or are influenced by circulating testosterone. To investigate the
      possible association between testosterone and cardiovascular risk, as defined by
      the Framingham score, a Veterans Affairs (VA) database was analyzed. METHODS: A
      retrospective chart review was performed. Inclusion criteria were male sex and
      age >= 20 years. Exclusion criteria included pre-existing cardiovascular disease,
      stroke, and diabetes. Data were collected on veterans who had total plasma
      testosterone checked in the year 2008. RESULTS: The study included 1,479 patients
      (mean age 61 years). Framingham score was negatively associated with both total
      testosterone (p < 0.0001) and free testosterone (p = 0.0003). There was a
      positive association between total testosterone and high-density lipoprotein and
      negative associations between total testosterone and body mass index (BMI), total
      cholesterol, triglycerides, and blood pressure medication use. Free testosterone
      was positively associated with total cholesterol, low-density lipoprotein, and
      current smoking status and negatively associated with age, BMI, and blood
      pressure medication use. The BMI was not associated with Framingham score.
      CONCLUSIONS: Lower plasma testosterone may suggest the presence of cardiovascular
      risk factors and potentially increased risk for heart disease.

PMID- 22364639
TI  - Special Interest Group on Cardiac Physiology established within the Scandinavian
      Physiological Society.

PMID- 22364637
TI  - Effects of dexpramipexole on brain mitochondrial conductances and cellular
      bioenergetic efficiency.
AB  - Cellular stress or injury can result in mitochondrial dysfunction, which has been
      linked to many chronic neurological disorders including amyotrophic lateral
      sclerosis (ALS) and Parkinson's disease (PD). Stressed and dysfunctional
      mitochondria exhibit an increase in large conductance mitochondrial membrane
      currents and a decrease in bioenergetic efficiency. Inefficient energy production
      puts cells, and particularly neurons, at risk of death when energy demands exceed
      cellular energy production. Here we show that the candidate ALS drug
      dexpramipexole (DEX; KNS-760704; ((6R)-4,5,6,7-tetrahydro-N6-propyl-2,6
      benzothiazole-diamine) and cyclosporine A (CSA) inhibited increases in ion
      conductance in whole rat brain-derived mitochondria induced by calcium or
      treatment with a proteasome inhibitor, although only CSA inhibited calcium
      induced permeability transition in liver-derived mitochondria. In several cell
      lines, including cortical neurons in culture, DEX significantly decreased oxygen
      consumption while maintaining or increasing production of adenosine triphosphate
      (ATP). DEX also normalized the metabolic profile of injured cells and was
      protective against the cytotoxic effects of proteasome inhibition. These data
      indicate that DEX increases the efficiency of oxidative phosphorylation, possibly
      by inhibition of a CSA-sensitive mitochondrial conductance.

PMID- 22364640
TI  - Signal termination: how many different ways can you hit the brakes in biological
      systems?

PMID- 22364641
TI  - Let 'em grow: the Yin and Yang of vessel growth.

PMID- 22364642
TI  - Serratin a new metabolite obtained from Serratia marcescens, a bacterium isolated
      from the microflora associated with banana plantations.
AB  - When cultures of Serratia marcescens, an enterobacteria isolated from the
      microflora associated with banana plantations incubated at 27 degrees C in a
      yeast-calcium carbonate-dextrose solid medium (10 g of yeast extract, 20 g
      dextrose, 15 g bacteriological agar, 20 g calcium carbonate and 1000 mL distilled
      water) were extracted with chloroform and purified by column chromatography, we
      obtained a new colourless bacterial metabolite which according to spectroscopic
      data proved to be serratin.

PMID- 22364643
TI  - A multimetallic piano-stool Ir-Sn3 catalyst for nucleophilic substitution
      reaction of gamma-hydroxy lactams through N-acyliminium ions.
AB  - A multimetallic piano-stool complex [Cp*Ir(SnCl(3))(2){SnCl(2)(H(2)O)(2)}] (1)
      having Ir-Sn(3) motif has been synthesized from [Cp*IrCl(2)](2) and SnCl(2). The
      multimetallic complex catalytically promotes the nucleophilic substitution
      reaction (here after alpha-amidoalkylation reaction) of gamma-hydroxylactams
      generated from phthalimidals to obtain decorated isoindolinones in excellent
      yields. Succinamidals, however, lead to the substituted pyrrolidinones
      (thermodynamic control product) via S(N)1-type path as well as eliminated
      pyrrolinones (kinetic control product) via an E1-type path, depending on the
      reaction parameters. A straightforward application of this methodology is to
      synthesize benzo-fused indolizidine alkaloid mimics.

PMID- 22364644
TI  - Surface fluorination of zirconia: adhesive bond strength comparison to commercial
      primers.
AB  - OBJECTIVE: This study evaluated contact angle and shear bond strength of three
      commercial zirconia primers and compared them to a recently developed
      fluorination pre-treatment. Earlier investigations reported that plasma
      fluorinated zirconia modifies the chemical bonding structure creating a more
      reactive surface. MATERIALS AND METHODS: Yttria-stabilized zirconia (LAVA, 3M
      ESPE) plates were highly polished using 3MUm diamond paste (R(a) ~200nm) prior to
      pretreatments. After primer and fluorination treatment, contact angles were
      measured to quantify surface hydrophobicity before and after ethanol clean.
      Additionally, simple shear bond tests were performed to measure the adhesion
      strength to a composite resin. RESULTS: Plasma fluorination produced the lowest
      contact angle (7.8 degrees ) and the highest shear bond strength (37.3MPa)
      suggesting this pretreatment facilitates a more "chemically" active surface for
      adhesive bonding. CONCLUSIONS: It is hypothesized that plasma fluorination
      increase hydroxylation at the surface, making it more reactive, thus allowing for
      covalent bonding between zirconia surface and resin cement. A strong correlation
      was observed between contact angle and adhesion strength for all specimens; a
      relationship which may help understand the frequency and modes of failures,
      clinically. It is also believed that this surface treatment can increase long
      term viability of zirconia restorations over other adhesive techniques.

PMID- 22364646
TI  - Safe high-pressure freezing of infectious micro-organisms.
AB  - We describe how high-pressure freezing of infectious biological material can
      safely be accomplished with the help of membrane carriers. The method described
      is easy to perform; however, careful manipulations are required. Existing safety
      regulations must still be followed. However, the procedure reduces the risk of
      dissemination of infectious material.

PMID- 22364647
TI  - Semiautomated QT interval measurement in electrocardiograms from a thorough QT
      study: comparison of the grouped and ungrouped superimposed median beat methods.
AB  - INTRODUCTION: We postulated that it may be easier to identify earliest Q onset
      and latest T offset when the median beats from 12 leads are separated vertically
      by 5 to 10 mm (ungrouped superimposed median beat [SMB] method) rather than when
      their baselines closely (but rarely perfectly) overlap (grouped SMB method).
      METHODS: Three readers manually adjudicated annotations placed by an automated
      algorithm, using grouped (gSMB) and ungrouped (uSMB) methods in 2658
      electrocardiograms (ECGs) recorded in 38 subjects in a crossover design thorough
      QT study at predose and 6 time points postdosing with placebo or moxifloxacin.
      RESULTS: Placebo-subtracted, moxifloxacin-induced QTcF prolongation was
      comparable with both methods. Maximum QTcF prolongation was seen at 2 hours--10.5
      milliseconds (90% confidence interval, 7.9-13.1 milliseconds) with gSMB and 12.9
      milliseconds (90% confidence interval, 9.9-15.8 milliseconds) by uSMB. Both
      methods showed good agreement; mean QT was 4 milliseconds greater by uSMB.
      Interreader variability of absolute differences in QT measurements was 1
      millisecond lower with the uSMB method (6.8 +/- 5.7 milliseconds by gSMB and 5.9
      +/- 4.5 milliseconds by uSMB). CONCLUSION: Mean QT was 4 milliseconds longer, and
      interreader variability, 1 millisecond lower with uSMB. Otherwise, both methods
      were comparable and detected the moxifloxacin effect.

PMID- 22364649
TI  - Mechanisms for CO production from CO2 using reduced rhenium tricarbonyl
      catalysts.
AB  - The chemical conversion of CO(2) has been studied by numerous experimental
      groups. Particularly the use of rhenium tricarbonyl-based molecular catalysts has
      attracted interest owing to their ability to absorb light, store redox
      equivalents, and convert CO(2) into higher-energy products. The mechanism by
      which these catalysts mediate reduction, particularly to CO and HCOO(-), is
      poorly understood, and studies aimed at elucidating the reaction pathway have
      likely been hindered by the large number of species present in solution. Herein
      the mechanism for carbon monoxide production using rhenium tricarbonyl catalysts
      has been investigated using density functional theory. The investigation
      presented proceeds from the experimental work of Meyer's group (J. Chem. Soc.,
      Chem. Commun.1985, 1414-1416) in DMSO and Fujita's group (J. Am. Chem. Soc.2003,
      125, 11976-11987) in dry DMF. The latter work with a simplified reaction mixture,
      one that removes the photo-induced reduction step with a sacrificial donor, is
      used for validation of the proposed mechanism, which involves formation of a
      rhenium carboxylate dimer, [Re(dmb)(CO)(3)](2)(OCO), where dmb = 4,4'-dimethyl
      2,2'-bipyridine. CO(2) insertion into this species, and subsequent rearrangement,
      is proposed to yield CO and the carbonate-bridged [Re(dmb)(CO)(3)](2)(OCO(2)).
      Structures and energies for the proposed reaction path are presented and compared
      to previously published experimental observations.

PMID- 22364648
TI  - Advance directives and physicians' orders in nursing home residents with dementia
      in Flanders, Belgium: prevalence and associated outcomes.
AB  - BACKGROUND: Advance care planning (ACP) is an important element of high-quality
      care in nursing homes, especially for residents having dementia who are often
      incompetent in decision-making toward the end of life. The aim of this study was
      describe the prevalence of documented ACP among nursing home residents with
      dementia in Flanders, Belgium, and associated clinical characteristics and
      outcomes. METHODS: All 594 nursing homes in Flanders were asked to participate in
      a retrospective cross-sectional postmortem survey in 2006. Participating homes
      identified all residents who had died over the last two months. A structured
      questionnaire was mailed to the nurses closely involved in the deceased
      resident's care regarding the diagnosis of dementia and documented care planning,
      i.e. advance patient directives, authorization of a legal representative, and
      general practitioners' treatment orders (GP orders). RESULTS: In 345 nursing
      homes (58% response rate), nurses identified 764 deceased residents with dementia
      of whom 62% had some type of documented care plan, i.e. advance patient
      directives in 3%, a legal representative in 8%, and GP orders in 59%.
      Multivariate logistic regression showed that the presence of GP orders was
      positively associated with receiving specialist palliative care in the nursing
      home (OR 3.10; CI, 2.07-4.65). Chances of dying in a hospital were lower if there
      was a GP order (OR 0.38; CI, 0.21-0.70). CONCLUSIONS: Whereas GP orders are
      relatively common among residents with dementia, advance patient directives and a
      legal representative are relatively uncommon. Nursing home residents receiving
      palliative care are more likely to have a GP order. GP orders may affect place of
      death.

PMID- 22364650
TI  - Systematic review of the role of a belly board device in radiotherapy delivery in
      patients with pelvic malignancies.
AB  - PURPOSE: This review analyses the literature concerning the influence of the
      patient position (supine, prone and prone on a belly board device (BB) on the
      irradiated small-bowel-volume (SB-V)) and the resulting morbidity of radiation
      therapy (RT) in pelvic malignancies. METHODS: A literature search was performed
      in MEDLINE, web of science and Scopus. RESULTS: Forty-six full papers were found,
      of which 33 met the eligibility criteria. Fifteen articles focussed on the
      irradiated SB-V using dose volume histograms (DVHs). Twenty-seven articles
      studied the patient setup in different patient positions. This review showed that
      a prone treatment position can result in a lower irradiated SB-V as compared to a
      supine position, but a more significant reduction of the SB-V can be reached by
      the additional use of a BB in prone position, for both 3D-CRT and IMRT treatment
      plans. This reduction of the irradiated SB-V might result in a reduced GI
      morbidity. The patient position did not influence the required PTV margins for
      prostate and rectum. CONCLUSIONS: The irradiated SB-V can be maximally reduced by
      the use of a prone treatment position combined with a BB for both 3D-CRT and
      IMRT, which might individually result in a reduction of GI-morbidity.

PMID- 22364651
TI  - Structural transformation and guest dynamics of methanol-loaded hydroquinone
      clathrate observed by temperature-dependent Raman spectroscopy.
AB  - The structural transformations and guest dynamics of methanol-loaded beta-form
      hydroquinone (HQ) clathrate were investigated using temperature-dependent Raman
      spectroscopy. Methanol-loaded beta-form HQ clathrate was obtained by
      recrystallization and characterized by elemental analysis, synchrotron X-ray
      diffraction, solid-state (13)C NMR spectroscopy, and Raman spectroscopy.
      Temperature-dependent Raman spectra of methanol-loaded beta-form HQ clathrate
      were measured in the temperature range 300-412 K at increments of 4 K. Although
      no significant changes were evident in the temperature range 300-376 K, abrupt
      changes in the relative intensity and shape of the Raman bands were observed
      between 380 and 412 K indicating the structural transition from methanol-loaded
      beta-form HQ clathrate to pure alpha-form HQ. Methanol molecules were gradually
      released from the beta-form HQ clathrate in the range 364-380 K. Upon returning
      to ambient conditions, the crystal structure of the HQ sample remained identical
      to that of pure alpha-form HQ. Therefore, the temperature-induced structural
      transition of methanol-loaded HQ clathrate is completely irreversible and alpha
      form HQ is more stable at ambient conditions.

PMID- 22364652
TI  - Alternating gender incongruity: a new neuropsychiatric syndrome providing insight
      into the dynamic plasticity of brain-sex.
AB  - Between the two extreme ends of human sexuality - male and female - lie a poorly
      understood and poorly studied spectrum of ambiguously defined sexual identities
      that are very much a part of the human condition but defy rigid classification.
      "Bigender" is a recently formed sub-category of transgenderism, describing
      individuals who experience a blending or alternation of gender states. While
      recognized nominally by the APA, no scientific work to our knowledge has
      addressed this fascinating condition, or proposed any physiological basis for it.
      In addition, the alternation aspect has not been proposed as a nosological entity
      distinct from blending. We present descriptive data suggesting that many bigender
      individuals experience an involuntary switching of gender states without any
      amnesia for either state. In addition, similar to transsexual individuals, the
      majority of bigender individuals experience phantom breasts or genitalia
      corresponding to the non-biologic gender when they are in a trans-gender state.
      Finally, our survey found decreased lateralization of handedness in the bigender
      community. These observations suggest a biologic basis of bigenderism and lead us
      to propose a novel gender condition, "alternating gender incongruity" (AGI). We
      hypothesize that AGI may be related to an unusual degree or depth of hemispheric
      switching and corresponding callosal suppression of sex appropriate body maps in
      parietal cortex- possibly the superior parietal lobule- and its reciprocal
      connections with the insula and hypothalamus. This is based on two lines of
      reasoning. First, bigender individuals in our survey sample reported an elevated
      rate of bipolar disorder, which has been linked to slowed hemispheric switching.
      We hypothesize that tracking the nasal cycle, rate of binocular rivalry, and
      other markers of hemispheric switching will reveal a physiological basis for AGI
      individuals' subjective reports of gender switches. Switching may also trigger
      hormonal cascades, which we are currently exploring. Second, we base our
      hypotheses on ancient and modern associations between the left and right
      hemispheres and the male and female genders. By providing a case of sharp brain
      sex shifts within individuals, we believe that the study of AGI could prove
      illuminating to scientific understanding of gender, body representation, and the
      nature of self.

PMID- 22364653
TI  - Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a
      consecutive cohort of 108 patients.
AB  - BACKGROUND: Prurigo nodularis Hyde (PN) is a highly pruritic condition due to a
      vicious circle of repeated itching and scratching. There are no representative
      clinical studies investigating comorbidities in a large collective of PN
      patients. OBJECTIVE: This pilot study aimed to investigate the exact distribution
      of the coexisting diseases in a large representative consecutive cohort of PN
      patients. METHODS: A total of 108 PN patients (36.1% male; mean age of 61.5 +/-
      16.7 years) were enrolled in the study. RESULTS: In 87.0% of patients, diseases
      underlying PN could be established (18.5% skin disease, 7.4% systemic origin,
      1.8% neurological diseases, 59.3% mixed origin). Due to several possible
      causative co-factors, the majority of patients were classified in the group of
      mixed origin (59.3%). In 53.1% of these patients, at least one dermatological
      factor was involved in the induction of PN. Interestingly, nearly half (46.3%) of
      all PN patients had either an atopic predisposition or atopic dermatitis as a
      single cause of PN (18.5%) or as one co-factor of PN of mixed origin (27.8%).
      Considering the different underlying diseases, there was no significant age or
      gender difference. CONCLUSION: PN does not seem to represent a characteristic
      symptom of one disease only. Multiple pruritogenic diseases are linked to
      evolution and improvement of PN upon treatment. Atopic predisposition is a major
      factor in nearly half of PN patients. The large collective of the present study
      helped detect a broad range of underlying diseases and thus to provide
      recommendations for rational diagnostics.

PMID- 22364654
TI  - prevalence and causes of blindness and low vision revisited after 5 years of eye
      care in Timor-Leste.
AB  - PURPOSE: To estimate the 2010 prevalence and causes of blindness and low vision
      among Timor-Leste adults aged >=40 years, and compare these to the results of a
      survey conducted 5 years previously. METHOD: A population-based cross-sectional
      survey used multistage cluster random sampling proportionate to size to identify
      50 clusters of 45 people each. Cause of vision loss was determined for each eye
      with presenting visual acuity worse than 6/18. RESULTS: A participation rate of
      89.5% (n = 2014) was achieved. The gender-age-domicile adjusted prevalence was
      7.7% (95% confidence interval [CI] 6.5, 8.8) for 6/60, and 3.6% (95% CI 2.7, 4.4)
      for 3/60 blindness (better eye presenting vision worse than 6/60 and 3/60,
      respectively) among Timorese aged >=40 years. Cataract caused most blindness
      (69.3% at 6/60). The population prevalence of low vision (better eye presenting
      vision of 6/60 or better, but worse than 6/18) was 13.6% (95%CI 12.1, 15.1), most
      caused by uncorrected refractive error (57.4%) or cataract (39.5%). The
      prevalence and causes of blindness were unchanged compared with 5 years earlier,
      but low vision was less common. CONCLUSION: Unusually for a developing country,
      Timor-Leste has initiated a cycle of evidence-based eye care in which, although
      with limitations, population data are periodically available for monitoring and
      planning.

PMID- 22364655
TI  - The need for emergency surgical treatment in carotid-related stroke in evolution
      and crescendo transient ischemic attack.
AB  - OBJECTIVE: The purpose of this study was to examine the safety of emergency
      carotid endarterectomy (CEA) in patients with carotid stenosis and unstable
      neurological symptoms. METHODS: This prospective, single-center study involved
      patients with stroke in evolution (SIE) or fluctuating stroke or crescendo
      transient ischemic attack (cTIA) related to a carotid stenosis >= 50% who
      underwent emergency surgery. Preoperative workup included National Institute of
      Health Stroke Scale (NIHSS) neurological assessment on admission, immediately
      before surgery and at discharge, carotid duplex scan, brain contrast-enhanced
      head computed tomography (CT) or magnetic resonance imaging (MRI). End points
      were perioperative (30-day) neurological mortality, NIHSS score variation, and
      hemorrhagic or ischemic stroke recurrence. Patients were evaluated according to
      clinical presentation (SIE or cTIA), timing of surgery, and presence of brain
      infarction on neuroimaging. RESULTS: Between January 2005 and December 2009, 48
      patients were submitted to emergency surgery. CEAs were performed from 1 to 24
      hours from onset of symptoms (mean, 10.16 +/- 7.75). Twenty-six patients
      presented an SIE with a worsening NIHSS score between admission and surgery, and
      22 presented >= 3 cTIAs with a normal NIHSS score (= 0) immediately before
      surgery. An ischemic brain lesion was detected in four patients with SIE and
      eight patients with cTIA. All patients with cTIA presented a persistent NIHSS
      normal score before and after surgery. Twenty-five patients with SIE presented an
      NIHSS score improvement after surgery. Mean NIHSS score was 5.30 +/- 2.81 before
      surgery and 0.54 +/- 0.77 at discharge in the SIE group (P < .0001). One patient
      with SIE had a hemorrhagic transformation of an undetected brain ischemic lesion
      after surgery, with progressive neurological deterioration and death (2%).
      CONCLUSIONS: Due to the absence of randomized controlled trials of CEA for
      neurologically unstable patients, data currently available do not support a
      policy of emergency CEA in those patients. Our results suggest that a fast
      protocol, including CT scans and carotid duplex ultrasound scans in
      neurologically unstable patients, could help identify those that can be safely
      submitted to emergency CEA.

PMID- 22364656
TI  - Valproate and the risk for congenital malformations: Is formulation and dosage
      regime important?
AB  - BACKGROUND: Use of valproate in pregnancy, especially in doses over 1000mg a day,
      is known to be associated with a higher risk for major congenital malformations
      compared with other antiepileptic drugs. We sought to investigate whether the
      increased risk could be minimised by using controlled release or divided daily
      doses of valproate. METHODS: The UK Epilepsy and Pregnancy Register is a
      prospective, observational and follow up study set up to determine the risks of
      major congenital malformations for infants exposed to antiepileptic drugs in
      utero. In this study we have extracted data for those pregnancies exposed to
      valproate in monotherapy. We have calculated malformation rates and relative
      risks as a function of valproate exposure. RESULTS: Outcome data were available
      for 1109 pregnancies exposed to valproate in monotherapy. Exposure to 1000mg a
      day or more of valproate was associated with almost double the risk of major
      congenital malformation compared with daily valproate doses below 1000mg daily
      (8.86% vs 4.88%, RR: 1.7; 95% CI: 1.1-2.9). There were no differences in the
      risks for malformations between standard release valproate and controlled release
      valproate preparations (RR: 1.11; 95% CI: 0.67-1.83) or for those exposed to
      single or multiple daily administrations (RR: 0.99, 95% CI: 0.58-1.70).
      CONCLUSION: Prescribing controlled release valproate or multiple daily
      administrations in pregnancy did not reduce the risk for malformations. Higher
      malformation rates observed with in utero exposure to valproate are more likely
      related to total daily dose, rather than peak serum levels.

PMID- 22364657
TI  - A 15-month-old boy with reduced consciousness and convulsion.

PMID- 22364658
TI  - Diagnosis and surgical management of the arterial myopericytoma.

PMID- 22364659
TI  - Rhizobium radiobacter: an unusual pathogen isolated on an active chronic ulcerous
      inflammation.

PMID- 22364660
TI  - Combined use of free and pedicled flaps for stomal recurrence after total
      laryngectomy.

PMID- 22364661
TI  - Squamous cell carcinoma arising in epidermoid cysts: report of four cases and
      review of the literature.
AB  - Epidermoid cysts are commonly encountered in clinical practice and while the
      majority are benign, isolated cases of premalignant and malignant conditions have
      been identified in their walls. We report four cases of squamous cell carcinoma
      arising in the walls of epidermoid cysts and review the literature.

PMID- 22364662
TI  - Treatment of blowout fracture: optimal treatment modality yet to be found?

PMID- 22364663
TI  - Dancing eyes and uvula after brain tumour extirpation--a sign of tumour
      progression?

PMID- 22364664
TI  - Influence of smoking on interleukin-1beta level, oxidant status and antioxidant
      status in gingival crevicular fluid from chronic periodontitis patients before
      and after periodontal treatment.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the impact of
      smoking on the relationship between interleukin-1 (IL-1beta) and oxidation in
      patients with periodontitis and response to nonsurgical periodontal therapy.
      MATERIAL AND METHODS: Data were obtained from 30 patients with generalized
      chronic periodontitis (15 smokers and 15 nonsmokers) and from 10 periodontally
      healthy controls. IL-1beta level, total oxidant status (TOS) and total
      antioxidant status (TAS) were recorded in gingival crevicular fluid. Probing
      depth, clinical attachment level, gingival and plaque indices and bleeding on
      probing were also measured. The gingival crevicular fluid and clinical parameters
      were recorded at baseline and 6 wk after periodontal treatment. RESULTS: The
      study showed statistically significant improvement of clinical parameters in both
      smokers and nonsmokers after periodontal treatment. Moreover, the baseline IL
      1beta levels were significantly higher in smokers compared with nonsmokers (p <
      0.05). After periodontal treatment, the IL-1beta levels were significantly
      reduced in both smokers and nonsmokers (p < 0.05). There were no significant
      differences in TOS and TAS between periodontitis patients and healthy controls at
      baseline and 6 wk after periodontal treatment. The level of IL-1beta in gingival
      crevicular fluid was positively correlated with TOS in both smokers and
      nonsmokers. CONCLUSIONS: Periodontal treatment improved the clinical parameters
      in both smokers and nonsmokers. The results confirm that periodontal therapy has
      an effect on IL-1beta levels in gingival crevicular fluid, but not on TOS and
      TAS.

PMID- 22364665
TI  - Towards an international system of professional recognition for public health
      nutritionists: a feasibility study within the European Union.
AB  - OBJECTIVE: To test the feasibility of a pan-European professional recognition
      system for public health nutrition. DESIGN: A multistage consultation process was
      used to test the feasibility of a model system for public health nutritionist
      certification. A review of existing national-level systems for professional
      quality assurance was conducted via literature review and a web-based search,
      followed by direct inquiries among stakeholders. This information was used to
      construct a consultation document circulated to key stakeholders summarising the
      rationale of the proposed system and inviting feedback about the feasibility of
      the system. Two consultation workshops were also held. The qualitative data
      gathered through the consultation were collated and thematically analysed.
      SETTING: Europe. SUBJECTS: Public health nutrition workforce stakeholders across
      twenty-nine countries in the European Union. RESULTS: One hundred and forty-five
      contacts/experts representing twenty-nine countries were contacted with responses
      received from a total of twenty-eight countries. The system proposed involved a
      certification system of professional peer review of an applicant's professional
      practice portfolio, utilising systems supported by information technology for
      document management and distribution similar to peer-review journals. Through the
      consultation process it was clear that there was overall agreement with the model
      proposed although some points of caution and concern were raised, including the
      need for a robust quality assurance framework that ensures transparency and is
      open to scrutiny. CONCLUSIONS: The consultation process suggested that the added
      value of such a system goes beyond workforce development to enhancing recognition
      of the important role of public health nutrition as a professional discipline in
      the European public health workforce.

PMID- 22364666
TI  - Multi heart-cutting two-dimensional liquid chromatography-atmospheric pressure
      photoionization-tandem mass spectrometry method for the determination of
      endocrine disrupting compounds in water.
AB  - The multi-heart-cutting two-dimensional liquid chromatography-tandem mass
      spectrometry method using atmospheric pressure photoionization has been developed
      and successfully validated for the determination of nine endocrine disrupting
      compounds in river water. The method is based on the use of two different reverse
      phase columns connected through a six-port two-position switching valve equipped
      with a 200 MUl loop. An orthogonal separation was achieved by proper selection of
      stationary phases, mobile phases, and the use of a gradient elution in both
      dimensions. The method shows excellent performance in terms of accuracy (86.2
      111.1%), precision (intra-batch: 6.7-11.2%, inter-batch: 7.2-13.5%), and
      sensitivity (1.2-7.1 ng l(-1)). Twenty real samples collected from the Loucka and
      the Svratka rivers were analyzed, the studied compounds were found in all Svratka
      samples (9.7-11.2 ng l(-1) for beta-estradiol, 7.6-9.3 ng l(-1) for estrone, and
      24.6-38.7 ng l(-1) for bisphenol A).

PMID- 22364667
TI  - Comprehensive multidimensional separations for the analysis of petroleum.
AB  - Petroleum analysis presents many unique challenges as a result of the
      overwhelming number of compounds present in petroleum samples. Consequently the
      use of multidimensional separation techniques will almost invariably be required
      in order to overcome these challenges. Within this paper we review recent
      developments in the application of comprehensive multidimensional techniques for
      petroleum analysis focusing on more recent applications. Basic instrumentation
      for various comprehensive multidimensional techniques is outlined along with an
      overview of a broad range of applications in both group-type and target molecule
      analyses for petroleum and biofuel analysis. In addition, strategies for data
      interpretation and chemometric analysis of multidimensional data are also
      reviewed.

PMID- 22364668
TI  - Partitioning behavior of amino acids in aqueous two-phase systems formed by
      imidazolium ionic liquid and dipotassium hydrogen phosphate.
AB  - Partition coefficients of amino acids, including glycine, alanine, 2-aminobutyric
      acid, valine, leucine, threonine, methinoine, tryptophan and tyrosine, in
      [C(n)mim]Br (n=4, 6, 8)+K(2)HPO(4) aqueous two-phase systems (ATPSs) have been
      determined, and the relative hydrophobicity of the equilibrium phases in the
      ionic liquids-based aqueous two-phase systems has been characterized by the Gibbs
      energies of transfer for methylene group from the bottom salt-rich phase to the
      top ionic liquid-rich phase. Based on these results, factors affecting the
      partitioning behavior of the amino acids have been investigated. It is shown that
      partition coefficients of the amino acids increase with the increase of
      hydrophobicity of the amino acids and the ionic liquids, solution pH value, tie
      line length of the ATPSs and temperature of the systems. The possible driving
      forces and the thermodynamic parameters for the partitioning of amino acids in
      the ionic liquids-based ATPSs have also been discussed.

PMID- 22364669
TI  - Optimization of an improved single-column chromatographic process for the
      separation of enantiomers.
AB  - This work addresses optimization of an improved single-column chromatographic
      (ISCC) process for the separation of guaifenesin enantiomers. Conventional feed
      injection and fraction collection systems have been replaced with customized
      components facilitating simultaneous separation and online monitoring with the
      ultimate objective of application of an optimizing controller. Injection volume,
      cycle time, desorbent flow rate, feed concentration, and three cut intervals are
      considered as decision variables. A multi-objective optimization technique based
      on genetic algorithm (GA) is adopted to achieve maximum productivity and minimum
      desorbent requirement in the region constrained by product specifications and
      hardware limitations. The optimization results along with the contribution of
      decision variables are discussed using Pareto fronts that identify non-dominated
      solutions. Optimization results of a similar simulated moving bed process have
      also been included to facilitate comparison with a continuous chromatographic
      process.

PMID- 22364670
TI  - Magnetic solid-phase extraction based on diphenyl functionalization of Fe3O4
      magnetic nanoparticles for the determination of polycyclic aromatic hydrocarbons
      in urine samples.
AB  - Superparamagnetic Fe(3)O(4) diphenyl nanoparticles were prepared according to a
      solvothernal procedure and characterized by X-ray diffraction, infrared
      spectroscopy, surface area measurements, scanning electron microscopy, X-ray
      photoelectron spectroscopy and transmission electron microscopy. The magnetic
      phases present in the nanoparticle samples were analyzed by thermomagnetic
      analysis and the samples' magnetic properties were studied by vibrating sample
      magnetometry. The resulting nanoparticles having an average diameter of 200 nm
      were then used as solid-phase extraction sorbent for the determination of
      polycyclic aromatic hydrocarbons in urine samples. Method validation proved the
      feasibility of the developed beads for the quantitation of the investigated
      analytes at trace levels obtaining lower limit of quantitation values in the ng/l
      range. A good precision with coefficients of variations always lower than 15% was
      obtained. Finally, the superior extraction performance of the synthesized
      nanoparticles with respect to commercially available beads was proved.

PMID- 22364671
TI  - Lung function tests in clinical decision-making.
AB  - In this article, we review the utility of the most common lung function tests
      (spirometry, reversibility test, peak expiratory flow, lung volumes, maximal
      respiratory pressure, carbon monoxide transference, arterial blood gas, 6-minute
      walk test and desaturation with exercise and ergospirometry) related to the most
      frequent pathologies (dyspnea of undetermined origin, chronic cough, asthma,
      COPD, neuromuscular diseases, interstitial diseases, pulmonary vascular diseases,
      pre-operative evaluation and disability evaluation). Our analysis has been
      developed from the perspective of decision-making, clinical interpretation or
      aspects that the physician should take into account with their use. Consequently,
      the paper does not deal with aspects of quality, technique or equipment, with the
      exception of when regarding costs as we believe that this is an important element
      in the decision-making process. The document is extensively supported by
      references from the literature.

PMID- 22364672
TI  - Acanthamoeba keratitis in South India: a longitudinal analysis of epidemics.
AB  - PURPOSE: In light of the increased incidence of contact lens associated
      Acanthamoeba keratitis in recent years, this study analyzed longitudinal trends
      of its incidence among predominantly non-contact lens wearers in a high-volume
      referral center in South India. METHODS: A retrospective analysis of microbiology
      laboratory records at the Aravind Eye Hospital from 1988-2009 was performed. The
      Maximum Excess Events Test (MEET) was used to identify epidemics of Acanthamoeba
      keratitis. RESULTS: There were a total of 38,529 unique cases of infectious
      keratitis evaluated over this time period, of which 372 were culture-positive for
      Acanthamoeba. Only three cases (0.9%) of Acanthamoeba keratitis occurred among
      contact lens wearers. MEET identified unique Acanthamoeba keratitis epidemics in
      1993 and 2002. CONCLUSION: Discrete epidemics of Acanthamoeba keratitis occurred
      among a rural, non-contact lens wearing, population in South India in 1993 and
      2002.

PMID- 22364673
TI  - Intoxication strategy of Helicobacter pylori VacA toxin.
AB  - VacA toxin from the cancer-inducing bacterium Helicobacter pylori is currently
      classified as a pore-forming toxin but is also considered a multifunctional
      toxin, apparently causing many pleiotropic cell effects. However, an increasing
      body of evidence suggests that VacA could be the prototype of a new class of
      monofunctional A-B toxins in which the A subunit exhibits pore-forming instead of
      enzymatic activity. Thus, VacA may use a peculiar mechanism of action, allowing
      it to intoxicate the human stomach. By combining the action of a cell-binding
      domain, a specific intracellular trafficking pathway and a novel mitochondrion
      targeting sequence, the VacA pore-forming domain is selectively delivered to the
      inner mitochondrial membrane to efficiently kill target epithelial cells by
      apoptosis.

PMID- 22364674
TI  - A closer look at the nitrogen next door: 1H-15N NMR methods for glycosaminoglycan
      structural characterization.
AB  - Recently, experimental conditions were presented for the detection of the N
      sulfoglucosamine (GlcNS) NHSO(3)(-) or sulfamate (1)H and (15)N NMR resonances of
      the pharmaceutically and biologically important glycosaminoglycan (GAG) heparin
      in aqueous solution. In the present work, we explore further the applicability of
      nitrogen-bound proton detection to provide structural information for GAGs.
      Compared to the detection of (15)N chemical shifts of aminosugars through long
      range couplings using the IMPACT-HNMBC pulse sequence, the more sensitive two
      dimensional (1)H-(15)N HSQC-TOCSY experiments provided additional structural
      data. The IMPACT-HNMBC experiment remains a powerful tool as demonstrated by the
      spectrum measured for the unsubstituted amine of 3-O-sulfoglucosamine (GlcN(3S)),
      which cannot be observed with the (1)H-(15)N HSQC-TOCSY experiment due to the
      fast exchange of the amino group protons with solvent. The (1)H-(15)N HSQC-TOCSY
      NMR spectrum reported for the mixture of model compounds GlcNS and N
      acetylglucosamine (GlcNAc) demonstrate the broad utility of this approach.
      Measurements for the synthetic pentasaccharide drug Arixtra(r) (Fondaparinux
      sodium) in aqueous solution illustrate the power of this NMR pulse sequence for
      structural characterization of highly similar N-sulfoglucosamine residues in GAG
      derived oligosaccharides.

PMID- 22364675
TI  - Impact of the CATIE trial on antipsychotic prescribing patterns at a state
      psychiatric facility.
AB  - INTRODUCTION: Results from the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) indicate that, with the exception of olanzapine, no
      substantial overall differences were identified between second generation
      antipsychotics (SGAs) and the first generation antipsychotic (FGA) perphenazine.
      METHODS: This study evaluated the effect of CATIE on antipsychotic prescribing. A
      retrospective review of 1807 adults with schizophrenia was conducted and relative
      quarterly percentages of FGA versus SGA prescriptions were calculated. RESULTS:
      Time series analysis did not identify significant differences in rates of FGA
      prescriptions. CONCLUSIONS: Critiques of the methods used in CATIE may have
      mitigated its potential impact on antipsychotic prescribing despite cost
      effectiveness of perphenazine treatment.

PMID- 22364676
TI  - Neonatal management and safe discharge of late and moderate preterm infants.
AB  - Late and moderate preterm infants form the majority of admissions for prematurity
      to special care neonatal nurseries. Although at risk for acute disorders of
      prematurity, they do not suffer the serious long term risks and chronic illnesses
      of the extremely premature. The special challenges addressed here are of
      transition and of thermal adaptation, nutritional compensation for postnatal
      growth restriction, the establishment of early feeding, and the avoidance of post
      discharge jaundice or apnea. These 'healthy' premature infants provide challenges
      for discharge planning, in that opportunities may be available for discharge well
      before the expected date of delivery, which should be pursued. Barriers to early
      discharge are rigid conservative protocols and unwarranted investigations;
      facilitators of discharge are individualized care by nurses expert in cue-based
      feeding, early management of the thermal environment, support of family
      preferences and encouragement of mother-baby interactions. Safe discharge depends
      on recognizing these opportunities and applying strategies to address them.

PMID- 22364677
TI  - School outcome, cognitive functioning, and behaviour problems in moderate and
      late preterm children and adults: a review.
AB  - A large number of children (6 to 11% of all births) are born at a gestational age
      between 32 and 36 weeks. Little is known of long term outcomes for these moderate
      and late preterm children. In this review, results of 28 studies on school
      outcome, cognitive functioning, behaviour problems, and psychiatric disorders are
      presented. Overall, more school problems, less advanced cognitive functioning,
      more behaviour problems, and higher prevalence of psychiatric disorders were
      found in moderate and late preterm born infants, children, and adults compared
      with full term peers. Suggestions for future research are discussed.

PMID- 22364678
TI  - Impact of multiple births on late and moderate prematurity.
AB  - Multiple gestations have an increased risk of pregnancy complications compared
      with singletons. Delay in childbearing and assisted reproductive techniques have
      remained common reasons for the increase in multiple gestations over the last few
      decades. Higher rates of both spontaneous and indicated preterm birth in twins
      and triplets lead to a significant proportion of the moderate preterm birth and
      late preterm birth rates. The article is a review of the causes of preterm birth
      and morbidities associated with these pregnancies.

PMID- 22364679
TI  - Economic costs associated with moderate and late preterm birth: primary and
      secondary evidence.
AB  - Despite constituting the vast majority of preterm births, relatively little is
      known about the clinical and economic outcomes of children born either moderately
      or late preterm. This paper outlines the economic consequences of moderate and
      late preterm birth for the health services, for other sectors of the economy, for
      families and carers and, more broadly, for society. The paper reviews both the
      peer-reviewed literature and additional sources for information on the economic
      consequences of moderate and late preterm birth. It then goes on to present the
      results of a decision-analytic modelling study that aimed to estimate the
      societal costs associated with moderate and late preterm birth throughout the
      childhood years. Finally, the requirements for future methodological and applied
      research in this area are briefly outlined.

PMID- 22364680
TI  - Uninfected but not unaffected: chronic maternal infections during pregnancy,
      fetal immunity, and susceptibility to postnatal infections.
AB  - Chronic infections during pregnancy are highly prevalent in some parts of the
      world. Infections with helminths, Trypanosoma cruzi, Plasmodium spp, and HIV
      might affect the development of fetal immunity and susceptibility to postnatal
      infections independently of in-utero transmission of the pathogens. Fetal
      adaptive immune responses are common in neonates who have been exposed to
      maternal infection during pregnancy but not infected themselves. Such responses
      could affect the development of immunity to the homologous pathogens and their
      control during the first few years of life. Fetal innate and regulatory responses
      might also affect immunity to unrelated pathogens and responses to vaccines.
      Strategies to improve child health should integrate the possible clinical
      implications of in-utero exposure to chronic maternal infections.

PMID- 22364681
TI  - Treatment outcome of dogs with meticillin-resistant and meticillin-susceptible
      Staphylococcus pseudintermedius pyoderma.
AB  - BACKGROUND: The prevalence of meticillin- and multidrug-resistant Staphylococcus
      pseudintermedius (MRSP) in canine pyoderma has been increasing in recent years;
      thus, treatment of these cases has become challenging. HYPOTHESIS/OBJECTIVES: To
      compare treatment outcome (clinical resolution and treatment duration), adverse
      effects of medication, and concurrent diseases and medications in dogs with
      meticillin-susceptible S. pseudintermedius (MSSP) and MRSP pyoderma.
      ANIMALS/METHODS: Medical records were reviewed retrospectively, and 123 MSSP and
      93 MRSP clinical cases between January 2008 and April 2010 were included.
      RESULTS: In MSSP infections, cefalexin and cefpodoxime were the most commonly
      prescribed antimicrobials, accounting for 43.2 and 34.4% of cases, respectively.
      In MRSP infections, chloramphenicol and doxycycline were most commonly
      prescribed, accounting for 52.6 and 14.4% of cases, respectively. Adverse effects
      were reported in seven MSSP and 31 MRSP cases. The most commonly reported adverse
      effects were gastrointestinal, prompting antibiotic discontinuation in three MSSP
      and 20 MRSP cases. Chloramphenicol was associated with the highest incidence of
      adverse reactions (27 of 51 cases). Of 164 cases with follow up, 43 of 88 MSSP
      infections and 29 of 76 MRSP infections achieved complete clinical resolution at
      the first recheck examination. Three MSSP and seven MRSP cases failed to improve
      or resolve at subsequent visits assessed at 3-4 week intervals. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Results from this study showed that the majority of
      pyodermas resolved regardless of meticillin susceptibility. Although some cases
      of MRSP pyoderma took longer to treat, this is likely to be because of chronicity
      and not the organism. In addition, adverse effects were frequently associated
      with chloramphenicol administration.

PMID- 22364682
TI  - Comparison of dental esthetic perceptions of young adolescents and their parents.
AB  - OBJECTIVES: To compare dental esthetic perceptions of adolescents at age 13 with
      those of parents and to assess associations with dental fluorosis. METHODS:
      Adolescents aged 13 underwent dental examinations for fluorosis on maxillary
      anterior teeth using the Fluorosis Risk Index. Adolescents and parents completed
      questionnaires concerning satisfaction with adolescents' dental appearance.
      McNemar and Bowker tests of symmetry were used for comparisons of esthetics
      ratings between parents and adolescents. Comparison of satisfaction between
      subjects with fluorosis and subjects with no fluorosis was made using Cochran
      Armitage Trend and Fisher's Exact tests. RESULTS: From 376 adolescents included
      in the study, 26 percent had definitive fluorosis, mostly at a mild level.
      Fifteen percent of adolescents were dissatisfied with dental appearance, and
      concerns were mainly about color (45 percent) and alignment (35 percent).
      Adolescents were less satisfied with overall dental appearance (P < 0.001) and
      color (P = 0.048) and more concerned about tooth shape (P = 0.002) than were
      their parents. Fluorosis status (yes/no) was not significantly associated with
      adolescents' perceptions (P > 0.05). Parents of subjects with fluorosis were more
      dissatisfied with dental appearance (P = 0.014) and color (P < 0.001) than other
      parents. The number of maxillary anterior zones exhibiting fluorosis was
      negatively associated with adolescent (P = 0.03) and parent (P = 0.002)
      satisfaction. CONCLUSION: Adolescents generally had less satisfaction with dental
      appearance and color, and were more concerned with tooth shape than were parents.
      For both parents and adolescents, decreased satisfaction was associated with the
      number of zones with definitive fluorosis.

PMID- 22364683
TI  - Possibility of scanning electron microscope observation and energy dispersive X
      ray analysis in microscale region of insulating samples using diluted ionic
      liquid.
AB  - The possibility of scanning electron microscope (SEM) observation and energy
      dispersive X-ray (EDX) spectrometry analysis in microscale regions of insulating
      samples using diluted ionic liquid was investigated. It is possible to obtain
      clear secondary electron images of insulating samples such as a rock and mineral
      at 5,000 times magnification by dropping 10 MUL of 1 wt% of 1-ethyl-3
      methylimidazolium acetate (EMI-CH3COO) diluted with ethanol onto the samples. We
      also obtained EDX spectra of the samples in microscale regions (~5 MUm2) without
      overlapping EDX spectra of other minerals with different composition. It might be
      possible to perform quantitative analysis of the samples if a method that does
      not need standard samples is applied or an X-ray detector sensitive for light
      elements was attached. The method of dropping 1 wt% EMI-CH3COO diluted with
      ethanol onto insulating samples is useful for SEM observation, EDX analysis in
      microscale regions, and the preservation of scarce rock and mineral samples
      because ionic liquid can be easily removed with acetone.

PMID- 22364684
TI  - Distribution of central corneal thickness and intraocular pressure in a large
      population of Turkish school children.
AB  - PURPOSE: To determine the distribution of central corneal thickness (CCT) and
      intraocular pressure (IOP) in a population of Turkish school children and to
      evaluate the relationships between these values and both age and gender. METHODS:
      A total of 30,320 eyes from 15,160 healthy school children aged 5-18 years were
      examined. CCT and IOP were measured using an ultrasonic pachymeter and a non
      contact tonometer, respectively. Measurements were compared with age, gender, and
      parental consanguinity of subjects. RESULTS: The mean age of the school children
      was 10.43 +/- 2.54 years. For right eyes, mean CCT was 557.91 +/- 34.26 um and
      mean IOP was 14.15 +/- 2.87 mmHg. Mean CCT was significantly thicker in males
      compared to females (P < 0.0001). Mean IOP was significantly higher in females
      compared to males (P < 0.0001). CCT in children aged 14 years and older was
      significantly thinner than that in the younger age groups (P < 0.0001). There was
      a significant difference among the age groups for IOP (P < 0.05). No significant
      differences were observed in CCT or IOP related to parental consanguinity (P =
      0.538, P = 0.319, respectively). CONCLUSION: Mean CCT in Turkish school children
      is of comparable thickness to that in Western school children. CCT reached adult
      values around 14 years of age in our children. Furthermore, males had thicker CCT
      than females. IOP was lower in males than females, and increased with age.

PMID- 22364686
TI  - SOS for veno-occlusive disease: defibrotide prophylaxis.

PMID- 22364685
TI  - Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric
      haemopoietic stem-cell transplantation: an open-label, phase 3, randomised
      controlled trial.
AB  - BACKGROUND: Hepatic veno-occlusive disease is a leading cause of morbidity and
      mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess
      whether defibrotide can reduce the incidence of veno-occlusive disease in this
      setting. METHODS: In our phase 3 open-label, randomised controlled trial, we
      enrolled patients at 28 European university hospitals or academic medical
      centres. Eligible patients were younger than 18 years, had undergone
      myeloablative conditioning before allogeneic or autologous HSCT, and had one or
      more risk factor for veno-occlusive disease based on modified Seattle criteria.
      We centrally assigned eligible participants on the basis of a computer-generated
      randomisation sequence (1:1), stratified by centre and presence of osteopetrosis,
      to receive intravenous defibrotide prophylaxis (treatment group) or not (control
      group). The primary endpoint was incidence of veno-occlusive disease by 30 days
      after HSCT, adjudicated by a masked, independent review committee, in eligible
      patients who consented to randomisation (intention-to-treat population), and was
      assessed with a competing risk approach. Patients in either group who developed
      veno-occlusive disease received defibrotide for treatment. We assessed adverse
      events to 180 days after HSCT in all patients who received allocated prophylaxis.
      This trial is registered with ClinicalTrials.gov, number NCT00272948. FINDINGS:
      Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the
      intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the
      defibrotide group had veno-occlusive disease by 30 days after HSCT compared with
      35 (20%) of 176 controls (risk difference -7.7%, 95% CI -15.3 to -0.1; Z test for
      competing risk analysis p=0.0488; log-rank test p=0.0507). 154 (87%) of 177
      patients in the defibrotide group had adverse events by day 180 compared with 155
      (88%) of 176 controls. INTERPRETATION: Defibrotide prophylaxis seems to reduce
      incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis
      could present a useful clinical option for this serious complication of HSCT.
      FUNDING: Gentium SpA, European Group for Blood and Marrow Transplantation.

PMID- 22364687
TI  - Small is beautiful: models of small neuronal networks.
AB  - Modeling has contributed a great deal to our understanding of how individual
      neurons and neuronal networks function. In this review, we focus on models of the
      small neuronal networks of invertebrates, especially rhythmically active CPG
      networks. Models have elucidated many aspects of these networks, from identifying
      key interacting membrane properties to pointing out gaps in our understanding,
      for example missing neurons. Even the complex CPGs of vertebrates, such as those
      that underlie respiration, have been reduced to small network models to great
      effect. Modeling of these networks spans from simplified models, which are
      amenable to mathematical analyses, to very complicated biophysical models. Some
      researchers have now adopted a population approach, where they generate and
      analyze many related models that differ in a few to several judiciously chosen
      free parameters; often these parameters show variability across animals and thus
      justify the approach. Models of small neuronal networks will continue to expand
      and refine our understanding of how neuronal networks in all animals program
      motor output, process sensory information and learn.

PMID- 22364688
TI  - Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics
      and social drinkers.
AB  - Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have
      been extensively studied in rodents, BDNF levels have rarely been measured in
      abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group
      comparisons of serum BDNF levels is difficult due to limited information
      regarding analytical variance, biological variability, and the relative
      contribution of platelet and plasma pools to serum BDNF. Analytical variance
      (intra- and inter-assay coefficients of variation) of the enzyme-linked
      immunosorbent assay (ELISA) was characterized. Within- and between-subject
      variability, and group differences in serum and plasma BDNF, was assessed on
      three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social
      drinkers (SDs; 8M/8F). Significantly higher mean (+/-sd) serum BDNF levels were
      observed for the AD group compared to the SD (p = 0.003). No significant
      difference in mean baseline plasma BDNF levels was observed between AD and SD
      groups. The low analytical variance, high day-to-day within-individual stability
      and the high degree of individuality demonstrates the potential clinical utility
      of measuring serum BDNF levels. The low correlations that we observed between
      plasma and serum levels are congruent with their representing separate pools of
      BDNF. The observation of higher basal serum BDNF in the AD group without a
      concomitant elevation in plasma BDNF levels indicates that the elevated serum
      BDNF in AD patients is not due to greater BDNF exposure. Further research is
      warranted to fully elucidate mechanisms underlying this alteration and determine
      the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol
      abuse.

PMID- 22364689
TI  - Determination of Trichinella spiralis in pig muscles using Mid-Fourier Transform
      Infrared Spectroscopy (MID-FTIR) with Attenuated Total Reflectance (ATR) and Soft
      Independent Modeling of Class Analogy (SIMCA).
AB  - The aim of this work was to study the feasibility of detection of Trichinella
      spiralis in swine meat using Middle Infrared Spectroscopy Fourier Transform with
      Attenuated Total Reflectance (ATR) and Soft Independent Modeling of Class Analogy
      (MID-FTIR-ATR-SIMCA). Five male Pigs were orally infected at different larvae
      concentrations (13,000, 6500, 3500, 1625, 812 larvae/pig) and after 24 weeks the
      animals were euthanized. Five types of muscles were studied (leg, loin, rib,
      masseter, and diaphragm). Results showed that MID-FTIR-ATR-SIMCA was useful to
      determine the presence of T. spiralis in the samples, as the interclass distance
      between infected and non infected muscles varied from 13.5 to 36.8. This
      technique was also useful to discriminate among pig muscles, where masseter
      showed the largest interclass distance, while rib presented the smallest one. In
      all cases the recognition and rejection rates were 100%, which means that the
      methodology is capable of accurately separating T. spiralis infected from non
      infected swine meat.

PMID- 22364690
TI  - Effect of torsemide and furosemide on clinical, laboratory, radiographic and
      quality of life variables in dogs with heart failure secondary to mitral valve
      disease.
AB  - OBJECTIVES: Diuretic therapy reduces preload and relieves congestion secondary to
      cardiac dysfunction. Torsemide (torasemide) is a loop diuretic with longer
      duration of action, decreased susceptibility to diuretic resistance, and
      adjunctive aldosterone antagonist properties compared with furosemide. We
      hypothesized that torsemide would be well tolerated and no less effective than
      furosemide at diuresis, control of clinical signs, and maintenance of quality of
      life (QOL) in dogs with congestive heart failure (CHF). ANIMALS, MATERIALS AND
      METHODS: Seven client-owned dogs with stable CHF receiving twice daily oral
      furosemide and adjunctive medications. Utilizing a double-blinded, randomized,
      crossover design, dogs were administered either oral furosemide at their current
      dose or an equivalent oral dose of torsemide (1/10 of the daily furosemide dose
      divided into twice daily dosing) on day 0. Crossover occurred at day 7 and the
      study ended on day 14. Clinical, laboratory, radiographic, and QOL variables were
      evaluated on days 0, 7 and 14. RESULTS: No dogs developed recurrent CHF during
      the study. Mean furosemide dose on day 0 was 5.13 mg/kg/day (range 2.8-9.6).
      Following torsemide treatment, creatinine (P = 0.020), urea nitrogen (P = 0.013),
      phosphorus (P = 0.032), albumin (P = 0.019), carbon dioxide (P = 0.015) and anion
      gap (P = 0.005) were significantly increased, and urine specific gravity (P =
      0.004) and chloride (P = 0.021) were significantly decreased compared with
      furosemide dosing. No differences in QOL were found. CONCLUSIONS: Results
      indicate that torsemide is equivalent to furosemide at controlling clinical signs
      of CHF in dogs and is likely to achieve greater diuresis vs. furosemide. Larger
      clinical trials evaluating torsemide as a first or second-line loop diuretic for
      congestive heart failure in dogs are warranted.

PMID- 22364691
TI  - Auscultatory, echocardiographic, biochemical, nutritional, and environmental
      characteristics of mitral valve disease in Norfolk terriers.
AB  - OBJECTIVES: In order to more fully understand degenerative mitral valve disease
      (DMVD) in the Norfolk terrier, we sought to characterize findings from the
      physical and echocardiographic examination; biochemical, biomarker, and
      nutritional profiles; and select environmental variables from a cohort of
      apparently healthy Norfolk terriers. ANIMALS, MATERIALS AND METHODS: Overtly
      healthy Norfolk terriers >= 6 yrs old were recruited by 3 different veterinary
      hospitals and underwent historical, physical, electrocardiographic (ECG), and
      2D/color-flow Doppler echocardiographic examinations. Anterior mitral valve
      leaflet length, maximal thickness, area, and degree of prolapse were measured or
      calculated from two-dimensional images. Blood samples were obtained for serum
      biochemistry, serum serotonin, plasma NT-proBNP, amino acid profile, C-reactive
      protein, and cardiac troponin I. RESULTS: Of the 48 dogs entered into the study,
      23 (48%) had murmurs, 2 (4%) had mid-systolic clicks, 11 (23%) had ECG P
      pulmonale, and 41 (85%) were deemed to have echocardiographic evidence of DMVD,
      including 18 Norfolk terriers without a murmur. Seven (15%), 28 (58%), and 13
      (27%) dogs were classified as normal (stage 0), International Small Animal
      Cardiac Health Council (ISACHC) stage 1a, and 1b, respectively. Mean indexed
      echocardiographic mitral leaflet thickness (P = 0.017), area (P = 0.0002),
      prolapse (P = 0.0004), and left atrial to aortic diameter (P = 0.01) were
      significantly different between ISACHC 0, 1a, and 1b. CONCLUSION: DMVD is
      relatively common in Norfolk terriers and echocardiographic changes consistent
      with mild DMVD can be seen in dogs without a heart murmur.

PMID- 22364692
TI  - Signaling pathways in mitral valve degeneration.
AB  - Heart valves exhibit a highly-conserved stratified structure exquisitely designed
      to counter biomechanical forces delivered over a lifetime. Heart valve structure
      and competence is maintained by heart valve cells through a process of continuous
      turnover extracellular matrix (ECM). Degenerative (myxomatous) mitral valve
      disease (DMVD) is an important disease associated with aging in both dogs and
      humans. DMVD is increasingly regarded as a disease with identifiable signaling
      mechanisms that control key genes associated with regulation and dysregulation of
      ECM homeostasis. Initiating stimuli for these signaling pathways have not been
      fully elucidated but likely include both mechanical and chemical stimuli.
      Signaling pathways implicated in DMVD include serotonin, transforming growth
      factor beta (TGFbeta), and heart valve developmental pathways. High circulating
      serotonin (carcinoid syndrome) and serotoninergic drugs are known to cause
      valvulopathy that shares pathologic features with DMVD. Recent evidence supports
      a local serotonin signaling mechanism, possibly triggered by high tensile loading
      on heart valves. Serotonin initiates TGFbeta signaling, which in turn has been
      strongly implicated in canine DMVD. Recent evidence suggests that degenerative
      aortic and mitral valve disease may involve pathologic processes that mimic
      osteogenesis and chondrogenesis, respectively. These processes may be mediated by
      developmental pathways shared by heart valves, bone, and cartilage. These
      pathways include bone morphogenic protein (BMP) and Wnt signaling. Other
      signaling pathways implicated in heart valve disease include Notch, nitric oxide,
      and angiotensin II. Ultimately, increased understanding of signaling mechanisms
      could point to therapeutic strategies aimed at slowing or halting disease
      progression.

PMID- 22364693
TI  - Static and cyclic tensile strain induce myxomatous effector proteins and
      serotonin in canine mitral valves.
AB  - OBJECTIVES: Degenerative (myxomatous) mitral valve disease is an important
      cardiac disease in dogs and humans. The mechanisms that initiate and propagate
      myxomatous pathology in mitral valves are poorly understood. We investigated the
      hypothesis that tensile strain initiates expression of proteins that mediate
      myxomatous pathology. We also explored whether tensile strain could induce the
      serotonin synthetic enzyme tryptophan hydroxylase 1 (TPH1), serotonin synthesis,
      and markers of chondrogenesis. ANIMALS: Mitral valves were obtained postmortem
      from dogs without apparent cardiovascular disease. METHODS: Mitral valves were
      placed in culture and subjected to 30% static or cyclic tensile strain and
      compared to cultured mitral valves subjected to 0% strain for 72 h. Abundance of
      target effector proteins, TPH1, and chondrogenic marker proteins was determined
      by immunoblotting. Serotonin was measured in the conditioned media by ELISA.
      RESULTS: Both static and cyclic strain increased (p < 0.05) expression of
      myxomatous effector proteins including markers of an activated myofibroblast
      phenotype, matrix catabolic and synthetic enzymes in canine mitral valves
      compared to unstrained control. Expression of TPH1 was increased in statically
      and cyclically strained mitral valves. Expression of chondrogenic markers was
      increased in statically strained mitral valves. Serotonin levels were higher (p <
      0.05) in media of cyclically strained valves compared to unstrained valves after
      72 h of culture. CONCLUSION: Static or cyclic tensile strain induces acute
      increases in the abundance of myxomatous effector proteins, TPH1, and markers of
      chondrogenesis in canine mitral valves. Canine mitral valves are capable of local
      serotonin synthesis, which may be influenced by strain.

PMID- 22364694
TI  - Retrospective review of carvedilol administration in 38 dogs with preclinical
      chronic valvular heart disease.
AB  - OBJECTIVES: Report the effect of carvedilol administration on clinical and
      echocardiographic parameters and outcome in dogs with preclinical (ACVIM Stage B)
      chronic valvular heart disease (CVD). ANIMALS, MATERIALS AND METHODS:
      Retrospective case series of 38 client-owned dogs. Demographic, physical
      examination and diagnostic imaging findings, blood pressure (BP), administration
      details and outcome were obtained from medical records of dogs receiving
      carvedilol for preclinical CVD. When possible, additional follow-up information
      was obtained through telephone interviews with referring veterinarians and
      owners. RESULTS: Baseline data and follow-up were evaluated. Median and
      interquartile range (IQR) for age and weight were 8.6 (7.2-10.8) years and 8.5
      (7.6-9.6)kg. 14/38 were male; 33/38 were Cavalier King Charles Spaniels; 33/38
      had Stage B2 CVD. The initial dose of carvedilol was 0.31 (0.26-0.35)mg/kg PO
      twice daily. The carvedilol dose achieved following up titration was 1.11 (0.81
      1.32)mg/kg twice daily. No adverse effects were recorded during up titration.
      Median survival for all dogs was 48.5 months with a 95% CI of 38.3-58.6.
      CONCLUSIONS: This study suggests that carvedilol at the dose reported herein is
      well tolerated in small breed dogs with preclinical CVD. Prospective studies to
      evaluate efficacy are warranted.

PMID- 22364695
TI  - Liver transplantation with preservation of the inferior vena cava: lessons
      learned through 2,000 cases.
AB  - BACKGROUND: We aim to demonstrate the utility and efficacy of the "piggyback
      technique" (PBT); liver transplant (LT) with caval preservation. STUDY DESIGN:
      Adult LTs were performed with intent to use the PBT except in cases of juxtacaval
      malignancy or technical difficulty. Hepatic venous outflow was established
      between the donor suprahepatic cava and the joined ostia of all recipient
      suprahepatic veins. Technical variants with the donor cava and recipient
      retrohepatic cava were used as needed. The experience was divided into 2 eras: E1
      (1994-2002), E2 (2002-2010). RESULTS: We completed 945 of 1080 LTs in E1 (87.5%)
      and 851 of 920 LTs in E2 (92.5%) using the PBT. Thirty day mortality was 4.6% in
      E1, 3% in E2 (p = 0.02) with 2 intra-operative deaths in E1. One, 3, 5 year
      patient survival was 83.7, 75.6, 69.3% in E1 vs. 86, 78.4, 73.8% in E2 (p =
      0.057). Graft survival was 77.7, 69, 62.3% in E1 vs. 84, 76.2, 71.2% in E2 (p <
      0.0001). Median operative time and hospital length of stay improved in E2 (p <
      0.0001, 0.0001). Outflow variants were used more frequently in E2 (11.3% vs.
      6.1%). Nine patients (0.5%) developed outflow obstruction, 6 in E1, and 3 in E2.
      Twice, it was recognized and corrected intraoperatively. Seven patients presented
      with refractory ascites. Six were successfully treated (4 balloon dilatation, 2
      surgical revision), one patient died after attempted dilatation. CONCLUSIONS: The
      PBT can be used as the preferred technique in adult LT. With experience, the
      technique was used more frequently, with more variants, with improved outcomes.
      Outflow obstruction was a rare complication.

PMID- 22364696
TI  - Bridging peripheral nerve defects with a tissue engineered nerve graft composed
      of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold.
AB  - Tissue engineered nerve grafts are considered as a promising alternative to
      autologous nerve grafts used for peripheral nerve repair. The differences between
      these two types of nerve grafts are mainly in the regenerative microenvironment
      established by them. To construct ideal tissue engineered nerve grafts, it is
      therefore required to develop a better way to introduce biochemical cues into a
      neural scaffold, as compared to single or combined use of support cells and
      growth factors. Here, we used a co-culture system of dorsal root ganglia and
      Schwann cells to create an in vitro formed nerve equivalent, which was introduced
      into a silk fibroin-based scaffold to furnish a tissue engineered nerve graft
      (TENG). At 4- and 12- weeks after the TENG was implanted to bridge a 10-mm-long
      sciatic nerve defect in rats, histological and functional assessments as well as
      Western blot analysis were performed to evaluate the influences of the TENG on
      peripheral nerve regeneration. We found that at an early stage of nerve
      regeneration, the TENG significantly accelerated axonal growth, and up-regulated
      expressions of N-cadherin and PMP22. Twelve weeks after nerve grafting, the TENG
      produced a further improved outcome of nerve regeneration and functional
      recovery, which was more close to that of the autologous nerve graft than that of
      the silk fibroin-based scaffold. The introduction of an in vitro cultured nerve
      equivalent into a scaffold might contribute to establishing a native-like
      microenvironment for nerve regeneration.

PMID- 22364697
TI  - The potential of laminin-2-biomimetic short peptide to promote cell adhesion,
      spreading and migration by inducing membrane recruitment and phosphorylation of
      PKCdelta.
AB  - Laminin alpha2 chain plays an important role in basement membrane assembly and
      peripheral myelinogenesis; however, the integrin binding motif within human
      laminin alpha2 chain and the signaling pathways downstream of this ligand
      receptor interaction are poorly understood. We identified a motif, RNIPPFEGCIWN
      (Ln2-LG3-P2), within LG3 domain of human laminin alpha2 chain as a major site for
      both alpha3beta1 integrin and cellular activities such as cell adhesion,
      spreading, and migration. Binding of alpha3beta1 integrin with Ln2-LG3-P2 induced
      the membrane recruitment of protein kinase Cdelta (PKCdelta) and stimulated its
      tyrosine phosphorylation. The cellular activities induced by Ln2-LG3-P2 and the
      phosphorylation of focal adhesion kinase (FAK) were inhibited by rottlerin, a
      PKCdelta inhibitor, but not by Go6976, a PKCalpha/beta inhibitor. These results
      indicate that RNIPPFEGCIWN motif within human laminin alpha2 chain is a major
      ligand for alpha3beta1 integrin, and that binding of alpha3beta1 integrin
      mediates cellular activities through membrane recruitment and tyrosine
      phosphorylation of PKCdelta and FAK phosphorylation.

PMID- 22364699
TI  - Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and
      therapy.
AB  - Tumor-targeted imaging and therapy have been the challenging issue in the
      clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles
      (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for
      simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were
      synthesized by chemical conjugation of aminated 5beta-cholanic acid, polyethylene
      glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was
      readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded
      hyaluronic acid nanoparticles (Ce6-HANPs), wherein in the loading efficiency of
      Ce6 was higher than 80%. The resulting Ce6-HANPs showed stable nano-structure in
      aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were
      rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may
      enable intracellular release of Ce6 at the tumor tissue. After an intravenous
      injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the
      tumor tissue via the passive targeting mechanism and specifically enter tumor
      cells through the receptor-mediated endocytosis based on the interactions between
      HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon
      laser irradiation, Ce6 which was released from the nanoparticles could generate
      fluorescence and singlet oxygen inside tumor cells, resulting in effective
      suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be
      successfully applied to in vivo photodynamic tumor imaging and therapy
      simultaneously.

PMID- 22364698
TI  - A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with
      transferrin and tamoxifen for treating brain gliomas.
AB  - A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized
      with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the
      interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain
      barrier (BBB) transportation and improving the drug accumulation in the glioma
      cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30
      PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of
      each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the
      interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6%
      at pH 7.4, indicating a comparatively fast drug release at weak acidic condition
      and stable state of the carrier at physiological environment. The in vitro assay
      of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM
      exhibited higher BBB transportation ability with the transporting ratio of 6.06%
      in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB
      model by the coactions of TfR-mediated endocytosis and the inhibition effect of
      TAM to the drug efflux transports. Moreover, it also displayed the in vitro
      accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume
      effectively reduced.

PMID- 22364700
TI  - Osteoinductive hydroxyapatite-coated titanium implants.
AB  - Previous studies have shown that heterotopic induction of bone formation by
      calcium phosphate-based macroporous constructs is set into motion by the geometry
      of the implanted substrata, i.e. a sequence of repetitive concavities assembled
      within the macroporous spaces. The aim of this study was to construct
      osteoinductive titanium implants that per se, and without the exogenous
      application of the osteogenic soluble molecular signals of the transforming
      growth factor-beta supergene family, would initiate the induction of bone
      formation. To generate intrinsically osteoinductive titanium implants for
      translation in clinical contexts, titanium grade Ti-6A1-4V cylinders of 15 mm in
      length and 3.85 mm in diameter, with or without concavities, were plasma sprayed
      with crystalline hydroxyapatite resulting in a uniform layer of 30 MUm in
      thickness. Before coating, experimental titanium implants were prepared with a
      sequence of 36 repetitive concavities 1600 MUm in diameter and 800 MUm in depth,
      spaced a distance of 1000 MUm apart. Mandibular molars and premolars were
      extracted to prepare edentulous mandibular ridges for later implantation. Planar
      and geometric hydroxyapatite-coated titanium constructs were implanted in the
      left and right edentulized hemi-mandibles, respectively, after a healing period
      of 7-8 months, 3 per hemi-mandible. Three planar and three geometric implants
      were implanted in the left and right tibiae, respectively; additionally, planar
      and geometric constructs were also inserted in the rectus abdominis muscle. Six
      animals were euthanized at 30 and 90 days after implantation; one animal had to
      be euthanized 5 days after surgery and the remaining animal was euthanized 31
      months after implantation. Undecalcified longitudinal sections were precision
      sawed, ground and polished to 40-60 MUm; all sections were stained with a
      modified Goldner's trichrome. Undecalcified specimen block preparation was
      performed using the EXAKT precision cutting and grinding system.
      Histomorphometric analyses of bone in contact (BIC) showed that on day 30 there
      was no difference between the geometric vs. planar control implants; on day 90,
      the ratio of BIC to surface within the geometric implants was greater than on the
      standard planar implants in both mandibular and tibial sites; 31 months after
      implantation, selected concavities cut into the geometric implants harvested from
      the rectus abdominis muscle showed the spontaneous induction of bone formation
      with mineralized bone surfaced by osteoid seams. These data in non-human primates
      indicate that geometrically-constructed plasma-sprayed titanium implants are per
      se osteogenic, the concavities providing a unique microenvironment to initiate
      bone differentiation by induction.

PMID- 22364701
TI  - Dual functionalized PVA hydrogels that adhere endothelial cells synergistically.
AB  - Cell adhesion molecules govern leukocyte-endothelial cell (EC) interactions that
      are essential in regulating leukocyte recruitment, adhesion, and transmigration
      in areas of inflammation. In this paper, we synthesized hydrogel matrices
      modified with antibodies against vascular cell adhesion molecule-1 (VCAM1) and
      endothelial leukocyte adhesion molecule-1 (E-Selectin) to mimic leukocyte-EC
      interactions. Adhesion of human umbilical vein ECs to polyvinyl alcohol (PVA)
      hydrogels was examined as a function of the relative antibody ratio (anti
      VCAM1:anti-E-Selectin) and substrate elasticity. Variation of PVA backbone
      methacrylation was used to affect hydrogel matrix stiffness, ranging from 130 to
      720 kPa. Greater EC adhesion was observed on hydrogels presenting 1:1 anti
      VCAM1:anti-E-Selectin than on gels presenting either arginine-glycine-asparagine
      (RGD) peptide, anti-VCAM1, or anti-E-Selectin alone. Engineered cell adhesion -
      based on complementing the EC surface presentation - may be used to increase the
      strength of EC-matrix interactions. Hydrogels with tunable and synergistic
      adhesion may be useful in vascular remodeling.

PMID- 22364702
TI  - Tissue regeneration in vivo within recombinant spidroin 1 scaffolds.
AB  - One of the major tasks of tissue engineering is to produce tissue grafts for the
      replacement or regeneration of damaged tissue, and natural and recombinant silk
      based polymer scaffolds are promising candidates for such grafts. Here, we
      compared two porous scaffolds made from different silk proteins, fibroin of
      Bombyx mori and a recombinant analog of Nephila clavipes spidroin 1 known as
      rS1/9, and their biocompatibility and degradation behavior in vitro and in vivo.
      The vascularization and intergrowth of the connective tissue, which was
      penetrated with nerve fibers, at 8 weeks after subcutaneous implantation in
      Balb/c mice was more profound using the rS1/9 scaffolds. Implantation of both
      scaffolds into bone defects in Wistar rats accelerated repair compared to
      controls with no implanted scaffold at 4 weeks. Based on the number of
      macrophages and multinuclear giant cells in the subcutaneous area and the number
      of osteoclasts in the bone, regeneration was determined to be more effective
      after the rS1/9 scaffolds were implanted. Microscopic examination of the
      morphology of the matrices revealed differences in their internal
      microstructures. In contrast to fibroin-based scaffolds, the walls of the rS1/9
      scaffolds were visibly thicker and contained specific micropores. We suggest that
      the porous inner structure of the rS1/9 scaffolds provided a better micro
      environment for the regenerating tissue, which makes the matrices derived from
      the recombinant rS1/9 protein favorable candidates for future in vivo
      applications.

PMID- 22364703
TI  - Usefulness of cardiac computed tomographic delayed contrast enhancement of the
      left atrial appendage before pulmonary vein ablation.
AB  - Left atrial appendage (LAA) contrast filling defects are commonly found in
      patients undergoing multidetector cardiac computed tomography (CCT) before
      catheter ablation of atrial fibrillation. Delayed CCT allows quantification of
      the LAA delayed/initial attenuation ratio and improves accuracy for LAA thrombus
      detection, which may obviate routine transesophageal echocardiography (TEE)
      before ablation. CCT with contrast-enhanced scans (initial CCT) and with
      noncontrast-enhanced scans (delayed CCT) was performed in 176 patients. LAA was
      evaluated for filling defects. LAA apex, left atrial (LA) body, and ascending
      aorta (AA) attenuations (Hounsfield units) were measured on initial and delayed
      cardiac computed tomograms to calculate LAA, LA, LAA/LA, and LAA/AA attenuation
      ratios. LAA, initial LAA/LA, and initial LAA/AA attenuation ratios differed
      significantly in patients with versus without filling defects on cardiac computed
      tomogram, those with atrial fibrillation versus normal sinus rhythm, and those
      with abnormal left ventricular ejection fraction versus larger LA volumes (p
      <0.05). In 70 patients (40%) who underwent TEE, 13 LAA filling defects were seen
      on initial cardiac computed tomogram. Two defects persisted on delayed cardiac
      computed tomogram and thrombus was confirmed on transesophageal echocardiogram.
      Sensitivity, specificity, and positive and negative predictive values of initial
      CCT for LAA thrombi detection were 100%, 84%, 15%, and 100%, respectively. With
      delayed CCT these values increased to 100%. Intraobserver and interobserver
      reproducibilities for cardiac computed tomographic measurements were good
      (intraclass correlation 0.72 to 0.97, kappa coefficients 0.93 to 1.00). In
      conclusion, delayed CCT provided an increase in diagnostic accuracy of CCT for
      detection of LAA thrombus in patients with atrial fibrillation before ablation,
      which may decrease the need for routine TEE before the procedure.

PMID- 22364704
TI  - Angiotensin-converting enzyme (ACE) inhibitor angioedema: the silent epidemic.

PMID- 22364705
TI  - Higher random plasma glucose level is associated with increased plasma cardiac
      troponin in emergency department patients with suspected acute coronary syndrome.

PMID- 22364706
TI  - Examination of isolated ventricular noncompaction (hypertrabeculation) as a
      distinct entity in adults.

PMID- 22364707
TI  - Prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) from
      skin and carriage sites of dogs after treatment of their meticillin-resistant or
      meticillin-sensitive staphylococcal pyoderma.
AB  - BACKGROUND: Meticillin-resistant staphylococci are significant pathogens in
      veterinary dermatology, yet longitudinal studies of the impact of routine
      antimicrobial therapy on emergence or resolution of resistance are lacking.
      OBJECTIVES: To determine the prevalence of meticillin-resistant staphylococci on
      skin and carriage sites in dogs with bacterial pyoderma and evaluate the
      prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP)
      colonization after successful treatment of pyoderma. ANIMALS: One hundred and
      seventy-three dogs that presented to a dermatology referral service with pyoderma
      and 41 healthy control dogs. METHODS: Skin, nasal and rectal swabs for bacterial
      culture were collected at the time of referral and after clinical resolution of
      the pyoderma. Meticillin resistance was confirmed by demonstration of penicillin
      binding protein 2a antigen. RESULTS: Initially, skin cultures yielded MRSP in 70
      (40.5%) dogs, meticillin-resistant Staphylococcus aureus (MRSA) in three (1.7%)
      and meticillin-resistant Staphylococcus schleiferi ssp. coagulans (MRSScoag) in
      five (2.9%). Samples collected from the nose and rectum (carriage sites) yielded
      MRSP in 59 (34.1%) dogs, MRSA in 11 (6.4%) and MRSScoag in seven (4.0%). One
      hundred and two dogs were available for follow-up cultures after clinical cure.
      Of 42 dogs initially diagnosed with MRSP pyoderma, MRSP was isolated at follow-up
      from skin in 19 (45.2%) and carriage sites in 20 (47.6%). Of 60 dogs that did not
      have MRSP pyoderma initially, MRSP was isolated post-treatment from the skin in
      17 (28.3%), and MRSP from carriage sites increased from 7.8% (initially) to 26.7%
      (P = 0.0022). CONCLUSIONS AND CLINICAL IMPORTANCE: Colonization by MRSP often
      persists after resolution of MRSP pyoderma. Acquisition of MRSP during treatment
      appears to be common.

PMID- 22364708
TI  - The pharmacology of dienogest.
AB  - Dienogest (DNG) is a 19-nortestosterone derivative (a C-19 progestogen) with a
      cyanomethyl instead of an ethinyl group at the C-17 position, which may make the
      compound elicit fewer hepatic effects than other C-19 nortestosterone
      derivatives. Its similarity to norethisterone is reflected in its high
      endometrial efficacy, which could explain the high stability of the menstrual
      cycle women achieve when they use DNG in combination with ethinyl estradiol (EE)
      or with estradiol valerate (E2V). Its strong endometrial efficacy underlies the
      use of DNG (on its own) to treat endometriosis, and gives it antiproliferative
      and anti-inflammatory effects in the treatment of endometriotic lesions.
      Properties derived from its C-19 derivative structure include its short plasma
      half-life, of about 10h (which means the drug is not accumulated), and its high
      oral bioavailability, of more than 90%. However, DNG also has some of the
      properties of typical of progesterone derivatives, including a lack of effect on
      the metabolic and cardiovascular systems, and considerable antiandrogenic
      activity, the latter increased by its lack of affinity to the sex-hormone binding
      globulin (SHBG), in contrast to other C-19 progestogens. DNG has no
      glucocorticoid and no antimineralocorticoid activity. It also has no
      antiestrogenic activity, which suggests that it should not antagonize estradiol's
      beneficial effects. This is important for its use in the treatment of
      endometriosis, because, due to DNG's low gonadotropic activity, E2 levels are not
      decreased to zero, in contrast to treatments with gonadotropin-releasing hormone
      (GnRH) analogues. This maintenance beneficial E2 effects is of particular
      importance for the general tolerability of the first contraceptive pill to use
      E2V instead of EE, although clinical endpoint studies are still ongoing. These
      studies are expected, on the basis of its pharmacology, to demonstrate the
      cardiovascular safety of the new pill.

PMID- 22364709
TI  - The pharmacology of nomegestrol acetate.
AB  - Nomegestrol acetate (NOMAC) is a 19-norprogesterone derivative with high
      biological activity at the progesterone receptor, a weak anti-androgenic effect,
      but with no binding to estrogen, glucocorticoid or mineralocorticoid receptors.
      At dosages of 1.5mg/day or more, NOMAC effectively suppresses gonadotropic
      activity and ovulation in women of reproductive age. Hemostasis, lipids and
      carbohydrate metabolism remain largely unchanged. In normal and cancerous human
      breast cells, NOMAC has shown favorable effects on estrogen metabolism. Like
      natural progesterone (but in contrast to some other synthetic progestogens), it
      does not appear stimulate the proliferation of cancerous breast cells. While
      there has been some experience of the use of NOMAC in combination with estrogens
      as a hormone replacement therapy, most of the data on the compound are reported
      in the context of its inclusion as a component of a new contraceptive pill
      comprising 2.5mg NOMAC combined with 1.5mg estradiol. Because of its strong
      endometrial efficacy, and due to its high antigonadotropic activity and long
      elimination half-life (about 50h), the contraceptive efficacy of the new pill is
      maintained even when dosages are missed. Furthermore, for the first time with a
      monophasic 24/4 regimen containing estradiol, cyclical stability can be achieved
      comparable with that obtained using pills containing ethinyl estradiol and
      progestogens like levonorgestrel or drospirenone. The addition of NOMAC to
      estradiol means that the beneficial effects of estrogen are not lost, which is of
      especial importance in relation to the cardiovascular system. On the basis both
      of its pharmacology and of studies performed during the development of the
      NOMAC/estradiol pill, involving some 4000 women in total, good long-term
      tolerability can be expected for NOMAC, although its safety profile is still to
      be fully ascertained, as the clinical endpoint studies are yet to be completed.

PMID- 22364711
TI  - Superparamagnetic and fluorescent thermo-responsive core-shell-corona hybrid
      nanogels with a protective silica shell.
AB  - We present the preparation and the characterization of the solution behavior and
      functional properties of superparamagnetic and/or fluorescent, thermo-responsive
      inorganic/organic hybrid particles with an intermediate protective silica shell
      and a smart polymer corona. These well-defined multifunctional nanogels were
      prepared via two consecutive encapsulation processes of superparamagnetic
      Fe(2)O(3) nanoparticles (NPs) and/or fluorescent CdSe(ZnS) semiconductor
      nanocrystals with a silica layer and a crosslinked poly(N-isopropylacrylamide)
      (PNIPAAm) polymer shell. First, the different NPs were entrapped into a silica
      shell using a microemulsion process. Therein, the precise adjustment of the
      conditions allows to entrap either several particles or single ones and to tailor
      the thickness of the silica shell in the range of 20-60 nm. In a second step, a
      polymer coating, i.e. thermosensitive PNIPAAm, was attached onto the surface of
      the multifunctional core-shell particles via free radical precipitation
      polymerization, furnishing multifunctional core-shell-corona hybrid nanogels.
      Analyses of the functional properties, i.e. optical brightness and magnetic
      moments, along with transmission electron microscopy reveal near monodisperse
      hybrid nanoparticles that retain the intrinsic properties of the original
      nanocrystals. Additionally, we demonstrate the drastically increased chemical
      stability due to the barrier properties of the intermediate silica layer that
      protects and shields the inner functional nanocrystals and the responsive
      character of the smart PNIPAAm shell.

PMID- 22364710
TI  - Hydroxyapatite-armored poly(epsilon-caprolactone) microspheres and hydroxyapatite
      microcapsules fabricated via a Pickering emulsion route.
AB  - Hydroxyapatite (HAp) nanoparticle-armored poly(epsilon-caprolactone) (PCL)
      microspheres were fabricated via a "Pickering-type" emulsion solvent evaporation
      method in the absence of any molecular surfactants. It was clarified that the
      interaction between carbonyl/carboxylic acid groups of PCL and the HAp
      nanoparticles at an oil-water interface played a crucial role in the preparation
      of the stable Pickering-type emulsions and the HAp nanoparticle-armored
      microspheres. The HAp nanoparticle-armored PCL microspheres were characterized in
      terms of size, size distribution, morphology, and chemical compositions using
      scanning electron microscopy, laser diffraction, energy dispersive X-ray
      microanalysis, and thermogravimetric analysis. The presence of HAp nanoparticles
      at the surface of the microspheres was confirmed by scanning electron microscopy
      and energy dispersive X-ray microanalysis. Pyrolysis of the PCL cores led to the
      formation of the corresponding HAp hollow microcapsules.

PMID- 22364712
TI  - Selective endovascular embolization for refractory idiopathic epistaxis is a safe
      and effective therapeutic option: technique, complications, and outcomes.
AB  - Epistaxis generally responds to conservative management, but a more invasive
      approach, such as superselective embolization, is sometimes justified. We report
      our experience with endovascular procedures in 19 patients from 2002 to 2011 for
      the treatment of refractory idiopatic posterior epistaxis. The sphenopalatine
      artery and distal internal maxillary arteries were embolized in all patients.
      Unilateral embolization was performed in 12 patients (63%), bilateral
      embolization in seven (37%). Additional embolization of the descending palatine
      artery was performed in eight patients (42%) and embolization of the facial
      artery and palatine arteries in four (21%). In one patient the distal ophthalmic
      artery was embolized with n-butyl cyanoacrylate. No minor or major complications
      occurred in relation to the embolization procedures. The average hospital stay
      was 11.1+/-8.6 days, including an average 5.2+/-3.4 days after embolization.
      Average follow-up after discharge was 21.3+/-25.7 months. Superselective
      endovascular embolization proved safe and effective in controlling idiopathic
      epistaxis, refractory to other maneuvers.

PMID- 22364713
TI  - Detrusorectomy reduces the need for augmentation and use of antimuscarinics in
      children with neuropathic bladders.
AB  - OBJECTIVE: To assess bladder behaviour and long-term outcome after detrusorectomy
      in children. MATERIAL AND METHODS: Between 1990 and 2001, 49 detrusorectomies
      were performed (mean follow-up: 9.6 years) in children with neuropathic bladders
      (mean age at surgery: 9.8 years). Urodynamic study (UDS) was done before surgery
      (pre-UDS) and after surgery (UDS-1 and UDS-2). Bladder behaviour was assessed as
      good, fair or poor depending on the volume and intravesical pressure. In all
      patients, oxybutynin and clean intermittent catheterization were used
      preoperatively. In 24 patients, good bladder compliance and capacity were seen
      before detrusorectomy. RESULTS: Good and fair outcomes were observed in 35 (71%)
      patients at 1 year and in 39 (79%) patients 6 years after detrusorectomy. In 30
      (60%) patients, there was hardly any difference between the first and second
      follow-up. In 9 (18%) patients, formal bowel bladder augmentation was necessary:
      in 6 (12%) because of poor compliance and in 3 because of small bladder volume
      and incontinence. Seven patients improved during follow-up, 5 of them after
      resuming oxybutynin. In 11 patients, oxybutynin could be stopped, and in 2 the
      dosage could be reduced to once daily. CONCLUSIONS: The good short-term results
      of detrusorectomy generally remain unchanged at long-term follow-up.
      Detrusorectomy can reduce the need for antimuscarinics, and the need for formal
      bladder augmentation in selected cases.

PMID- 22364715
TI  - Stakeholders involvement by HTA Organisations: why is so different?
AB  - OBJECTIVE: To investigate stakeholder involvement by Health Technology Assessment
      Organisations (HTAOs) in France, Spain, England and Wales, Germany, Sweden, and
      The Netherlands and to examine whether this involvement depends on (i) the
      administrative tradition and the relevant conception of the relationship between
      state and society (contractarian and corporative vs. organic), (ii) the general
      structure of the healthcare system (HCS) (Bismarckian vs. Beveridgian system),
      and (iii) the role of Health Technology Assessment (HTA) and HTAOs in the HCS.
      METHODS: Given the exploratory nature of the study, we considered interviews
      based on semi-structured questionnaires the most appropriate data-gathering
      technique. The interviews were administered to 16 key personnel in the HTAOs
      concerned. We have also carried out a literature review on HTAOs and stakeholders
      (1999-2011) using PubMed, Ebsco, JSTOR and Wiley Science. RESULTS: In
      contractarian and (to a lesser extent) Bismarckian models, stakeholders are more
      involved. The administrative tradition and the HCS appear less important when the
      HTA is binding and used for regulatory purposes. In such situations, stakeholders
      are more intensively involved because their participation provides an opportunity
      for HTAOs to achieve consensus and legitimacy in advance. CONCLUSIONS: Despite
      the limitations of the research (we did not conduct multiple interviews for each
      HTAO, and key informants were not always available) and its exploratory nature,
      we can conclude that models of stakeholders involvement cannot easily be
      transferred from one country to another due to the importance of national
      administrative traditions and the characteristics of HCSs.

PMID- 22364714
TI  - Percutaneous insertion of double-J ureteral stent in children with ureteral
      obstruction: our experiences.
AB  - OBJECTIVE: Ureteral obstruction (UO) is usually treated by surgical or endoscopic
      approaches. We investigated whether percutaneous anterograde treatment with
      insertion of double-J ureteral stent (DJ) is a feasible alternative technique for
      the management of UO in selected cases, where traditional approaches are not
      possible or too risky. PATIENTS AND METHODS: The DJ was percutaneously inserted
      into 10 children (mean age 9 years) who suffered from UO. Three children had
      already been treated surgically for complex urotract congenital anomalies; six
      children had restenosis/reocclusion or stenosis of ureteropelvic junction; and
      one girl suffered migration of an intraoperatively placed DJ with stenosis of the
      distal ureter. RESULTS: Percutaneous insertion of the DJ was successful on the
      first attempt in 8 and on the second in 2 children. Adverse events after the
      procedure, all successfully treated, included one pyelonephritis and one
      migration of DJ, and 3 children had bacteriuria and 3 hematuria. Mean duration of
      insertion of the DJ was 6.4 months. After removal of the DJ, 7 children did not
      need any further interventions, but 2 children needed surgical correction and 1
      reinsertion of the DJ. CONCLUSION: In selected cases, percutanous insertion of a
      DJ should be considered as an alternative to surgery or endoscopic treatment in
      the management of children with UO.

PMID- 22364716
TI  - Diffusion and activity of antibiotics against Burkholderia pseudomallei biofilms.
AB  - The diffusion and activity of ceftazidime (CAZ), imipenem (IPM) and
      trimethoprim/sulfamethoxazole (TMP/SMX) against Burkholderia pseudomallei
      biofilms were comparatively tested using the high biofilm-producing strain B.
      pseudomallei 377 and the biofilm-defective mutant B. pseudomallei M6. Biofilms
      were generated by inoculation of bacteria on polycarbonate membranes placed on
      the surface of tryptic soy agar plates. The results showed that diffusion of
      TMP/SMX through B. pseudomallei biofilms was similar for both strains. However,
      diffusion of CAZ and IPM was significantly faster through strain M6 biofilm in
      comparison with strain 377 biofilm. The viabilities of strain 377 biofilm were
      significantly higher than those observed with strain M6 for all antibiotics
      challenged at 4 h, suggesting that the biofilm-forming capacity may be involved
      in antibiotic susceptibilities in B. pseudomallei. These results re-emphasise the
      importance of biofilm for antibiotic resistance in B. pseudomallei.

PMID- 22364717
TI  - Efficacy of tigecycline and vancomycin in experimental catheter-related
      Staphylococcus epidermidis infection: microbiological and electron microscopic
      analysis of biofilm.
AB  - Central venous catheters are frequently used. The commonest cause of catheter
      related bloodstream infections (CRBSI) is coagulase-negative staphylococci (CoNS)
      associated with adherent biofilm. Tigecycline, a derivative of tetracycline, acts
      against strains producing biofilm. In this study, we aimed to determine the
      effect of tigecycline in a CRBSI model. A single dose of 10(8) colony-forming
      units (CFU)/mL of slime-producing Staphylococcus epidermidis was given through
      polyethylene catheters inserted into 24 rabbits. After 72 h, groups of eight
      rabbits were treated with heparin, vancomycin/heparin or tigecycline/heparin.
      Blood obtained from peripheral veins and the catheter lumen as well as catheter
      tips were cultured, and three catheters from each group were studied using
      electron microscopy. Surfaces were randomly subdivided and areas with >=50
      bacteria were compared. Blood cultures were positive from all heparin-treated
      rabbits but were negative from those receiving either antibiotic (P<0.001).
      Catheter tip cultures revealed growth from six, two and one rabbit(s) given
      heparin, vancomycin and tigecycline, respectively. Electron microscopy showed
      that catheters from heparin-treated rabbits were most heavily colonised (more
      areas with >=50 CFU) compared with catheters from animals treated with vancomycin
      or tigecycline (P<0.003 and P<0.001, respectively). In conclusion, this study
      shows that tigecycline and vancomycin are both effective for treating CRBSI due
      to CoNS. Electron microscopy of catheters themselves suggests that tigecycline is
      superior to vancomycin (P<0.001). Tigecycline may be useful for the treatment of
      CRBSI.

PMID- 22364718
TI  - A negative stain for electron microscopic tomography.
AB  - While negative staining can provide detailed, two-dimensional images of
      biological structures, the potential of combining tomography with negative
      staining to provide three-dimensional views has yet to be fully realized. Basic
      requirements of a negative stain for tomography are that the density and atomic
      number of the stain are optimal, and that the stain does not degrade or rearrange
      with the intensive electron dose (~106 e/nm2) needed to collect a full set of
      tomographic images. A commercially available, tungsten-based stain appears to
      satisfy these prerequisites. Comparison of the surface structure of negatively
      stained influenza A virus with previous structural results served to evaluate
      this negative stain. The combination of many projections of the same structure
      yielded detailed images of single proteins on the viral surface. Corresponding
      surface renderings are a good fit to images of the viral surface derived from
      cryomicroscopy as well as to the shapes of crystallized surface proteins.
      Negative stain tomography with the appropriate stain yields detailed images of
      individual molecules in their normal setting on the surface of the influenza A
      virus.

PMID- 22364719
TI  - How prevalent is macular telangiectasia type 2?

PMID- 22364721
TI  - Pulmonary hypertension in canine degenerative mitral valve disease.
AB  - Pulmonary hypertension secondary to degenerative mitral valve disease has been
      recognized clinically for many years in veterinary medicine, and clinical
      diagnosis of this syndrome in dogs has been enhanced greatly by widespread use of
      echocardiography and Doppler echocardiography. Medical therapy is now available
      to treat this clinical complication of mitral valve disease, making timely
      diagnosis even more important to patient longevity and quality of life.

PMID- 22364720
TI  - Differentiating the aging of the mitral valve from human and canine myxomatous
      degeneration.
AB  - During the course of both canine and human aging, the mitral valve remodels in
      generally predictable ways. The connection between these aging changes and the
      morbidity and mortality that accompany pathologic conditions has not been made
      clear. By exploring work that has investigated the specific valvular changes in
      both age and disease, with respect to the cells and the extracellular matrix
      found within the mitral valve, heretofore unexplored connections between age and
      myxomatous valve disease can be found. This review addresses several studies that
      have been conducted to explore such age and disease related changes in
      extracellular matrix, valvular endothelial and interstitial cells, and valve
      innervation, and also reviews attempts to correlate aging and myxomatous disease.
      Such connections can highlight avenues for future research and help provide
      insight as to when an individual diverts from an aging pattern into a diseased
      pathway. Recognizing these patterns and opportunities could result in earlier
      intervention and the hope of reduced morbidity and mortality for patients.

PMID- 22364722
TI  - Pathology, protein expression and signaling in myxomatous mitral valve
      degeneration: comparison of dogs and humans.
AB  - Myxomatous degenerative mitral valve disease (MMVD) is a common heart disease in
      dogs. Although several morphological similarities occur between human and canine
      MMVD differences exist. However, in advanced stages the accumulation of
      proteoglycans is the main finding in both species. The extracellular matrix (ECM)
      in normal canine and human mitral valves is similar. In MMVD of both species
      proteoglycans is the major alteration, although specific changes in collagen
      distribution exists. The valvular expression pattern of matrix metalloproteinases
      (MMPs) and of their inhibitors (TIMPs) differs, in part, between dogs and humans.
      The MMPs and TIMPs expression patterns are similar in normal canine and human
      mitral valves, but they are quite different during degenerative progression.
      Valve endothelial cells (VEC) and interstitial cells (VIC) are phenotypically
      transformed in canine and human MMVD. Inflammation is an unlikely cause of valve
      degeneration in humans and dogs. There are several lines of evidence suggesting
      that transforming growth factor beta1 (TGF beta1) and serotonin signaling may
      mediate valve degeneration in humans and dogs. Although human and canine MMVD
      share structural similarities, there are some differences in ECM changes, enzyme
      expression and cell transformation, which may reflect a varied pathogenesis of
      these diseases.

PMID- 22364724
TI  - Electrode and brain modeling in stereo-EEG.
AB  - OBJECTIVE: To quantify the perturbation due to the presence of a measuring depth
      electrode on the intracranial electric potential distribution, and to study the
      effect of the heterogeneity and anisotropy of the brain tissues' electric
      conductivity. METHODS: The governing differential equations are solved with the
      Boundary Elements Method to compute the perturbation on the electric potential
      distribution caused by the presence of the measuring electrode, and with the
      Finite Elements Method to simulate measurements in an heterogeneous anisotropic
      brain model. RESULTS: The perturbation on the measured electric potential is
      negligible if the source of electric activity is located more than approximately
      1mm away from the electrode. The error induced by this perturbation in the
      estimation of the source position is below 1mm in all tested situations. The
      results hold for different sizes of the electrode's contacts. The effect of the
      brain's heterogeneity and anisotropy is more important. In a particular example
      simulated dipolar sources in the gray matter show localization differences of up
      to 5mm between homogeneous isotropic and heterogeneous anisotropic brain models.
      CONCLUSIONS: It is not necessary to include detailed electrode models in order to
      solve the stereo-EEG (sEEG) forward and inverse problems. The heterogeneity and
      anisotropy of the brain electric conductivity should be modeled if possible. The
      effect of using an homogeneous isotropic brain model approximation should be
      studied in a case by case basis, since it depends on the electrode positions, the
      subject's electric conductivity map, and the source configuration. SIGNIFICANCE:
      This simulation study is helpful for interpreting the sEEG measurements, and for
      choosing appropriate electrode and brain models; a necessary first step in any
      attempt to solve the sEEG inverse problem.

PMID- 22364723
TI  - Involuntary paretic wrist/finger flexion forces and EMG increase with shoulder
      abduction load in individuals with chronic stroke.
AB  - OBJECTIVE: Clinical observations of the flexion synergy in individuals with
      chronic hemiparetic stroke describe coupling of shoulder, elbow, wrist, and
      finger joints. Yet, experimental quantification of the synergy within a shoulder
      abduction (SABD) loading paradigm has focused only on shoulder and elbow joints.
      The paretic wrist and fingers have typically been studied in isolation.
      Therefore, this study quantified involuntary behavior of paretic wrist and
      fingers during concurrent activation of shoulder and elbow. METHODS: Eight
      individuals with chronic moderate-to-severe hemiparesis and four controls
      participated. Isometric wrist/finger and thumb flexion forces and wrist/finger
      flexor and extensor electromyograms (EMG) were measured at two positions when
      lifting the arm: in front of the torso and at maximal reaching distance. The task
      was completed in the ACT(3D) robotic device with six SABD loads by paretic, non
      paretic, and control limbs. RESULTS: Considerable forces and EMG were generated
      during lifting of the paretic arm only, and they progressively increased with
      SABD load. Additionally, the forces were greater at the maximal reach position
      than at the position front of the torso. CONCLUSIONS: Flexion of paretic wrist
      and fingers is involuntarily coupled with certain shoulder and elbow movements.
      SIGNIFICANCE: Activation of the proximal upper limb must be considered when
      seeking to understand, rehabilitate, or develop devices to assist the paretic
      hand.

PMID- 22364725
TI  - Biodiversity of antifungal lactic acid bacteria isolated from raw milk samples
      from cow, ewe and goat over one-year period.
AB  - Antifungal lactic acid bacteria (ALAB) biodiversity was evaluated in raw milk
      from ewe, cow and goat over one year period. Lactic acid bacteria were enumerated
      using 8 semi-selective media, and systematically screened for their antifungal
      activity against 4 spoilage fungi commonly encountered in dairy products.
      Depending on the selective medium, between 0.05% (Elliker agar) and 5.5% (LAMVAB
      agar) screened colonies showed an antifungal activity. The great majority of
      these active colonies originated from cow (49%) and goat (43%) milks, whereas
      only 8% were isolated from ewe milk. Penicillium expansum was the most frequently
      inhibited fungus with 48.5% of colonies active against P. expansum among the 1235
      isolated, followed by Mucor plumbeus with 30.6% of active colonies, Kluyveromyces
      lactis with only 12.1% of active colonies and Pichia anomala with 8.7% of active
      colonies. In the tested conditions, 94% of the sequenced active colonies belonged
      to Lactobacillus. Among them, targeted fungal species differed according to the
      Lactobacillus group, whose presence largely depended on year period and milk
      origin. The Lb. casei and Lb. reuteri groups, predominantly recovered in
      summer/fall, were overrepresented in the population targeting M. plumbeus,
      whereas isolates from the Lb. plantarum group, predominantly recovered in spring,
      were overrepresented in the population targeting K. lactis, the ones belonging to
      the Lb. buchneri group, predominantly recovered in spring, were overrepresented
      in the population targeting P. anomala. Raw milk, especially cow and goat milks
      from the summer/fall period appeared to be a productive reservoir for antifungal
      lactobacilli.

PMID- 22364726
TI  - FoxP3+, and not CD25+, T cells increase post-transplant in islet allotransplant
      recipients following anti-CD25+ rATG immunotherapy.
AB  - Anti-CD25 antibodies are used as an induction therapy in islet
      allotransplantation for type 1 diabetes. Although previous reports suggested that
      anti-CD25 treatment may lead to depletion of CD4+CD25+ regulatory T cells (Tregs)
      and questioned its use in tolerance-promoting protocols for transplantation, the
      effect of anti-CD25 antibodies on the frequency and function of Tregs remains
      unclear. We examined the effect of anti-CD25 antibody, daclizumab, in vivo on
      Tregs in islet allograft recipients enrolled in a single-center study and
      monitored post-transplant. Our data shows that the reduction in CD25+ Treg cells
      observed post-transplant is due to masking of CD25 receptor by daclizumab and not
      due to depletion. In addition, using Treg marker, FoxP3, we show that anti-CD25+
      ATG treatment leads to an increase in FoxP3+ Tregs post-transplant. These data
      suggest that anti-CD25-based therapy has beneficial effects on Tregs and combined
      with ATG may be a promising therapy for autoimmunity and transplantation.

PMID- 22364727
TI  - Perfectionism, narcissism, and depression in suicidal and nonsuicidal adolescent
      inpatients.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between 2
      psychological profiles: (a) the intrapersonal profile, involving self-critical
      depression, self-oriented perfectionism, and narcissism, and (b) the
      interpersonal profile, involving dependent depression and socially prescribed
      perfectionism, and the association of these 2 profiles with suicidal behavior
      among adolescent inpatients. METHODS: One hundred adolescents, admitted to a
      university-affiliated psychiatric adolescent inpatient unit in Israel, completed
      the Depressive Experience Questionnaire for Adolescents, the Child and Adolescent
      Perfectionism Scale, and the Narcissistic Personality Inventory. The Suicidal
      Potential Interview was used to evaluate suicidal behavior and separate them into
      low-risk and high-risk groups. RESULTS: Dependent depression correlated
      positively and significantly with severity of suicidal behavior. Adolescent
      inpatients with high levels of suicidal behavior (n = 54) were more dependent in
      terms of depression and were more inclined to socially prescribed perfectionism
      compared with adolescent inpatients with low levels of suicidal behavior (n =
      45). The components of the intrapersonal profile did not correlate with severity
      of suicidal behavior; however, low narcissism scores characterized the
      psychological function that strongly predicted severe suicidal behavior.
      CONCLUSIONS: The findings indicated that the conceptualization of 2 broad
      intrapersonal and interpersonal profiles in adolescent inpatients may have some
      validity in terms of the interpersonal dimension. The components of the
      interpersonal profile related to severe suicidal behavior and may be important in
      planning treatment strategy.

PMID- 22364728
TI  - Temperature-responsive poly(N-isopropylacrylamide)-grafted microcarriers for
      large-scale non-invasive harvest of anchorage-dependent cells.
AB  - Cell cultivation on the surface of microcarriers in stirred suspension is an
      essential method for the large-scale culture of anchorage-dependent cells. For
      applying this method to the field of cell therapy and for obtaining a large
      number of intact cells, non-invasive cell harvest without proteolytic enzyme
      treatment is an advantageous method. In this regard, temperature-responsive
      microcarriers that bearing poly(N-isopropylacrylamide) (PIPAAm)-grafted chains on
      the outermost surface were developed for harvesting cultured cells by temperature
      alteration. PIPAAm-grafted beads with the various grafted amount of PIPAAm and
      various bead diameters were synthesized for optimizing cell proliferation and
      thermally-induced detachment on the surface. The chinese hamster ovary (CHO-K1)
      cells adhered on the surface of all PIPAAm-grafted beads at 37  degrees C, while
      the adhering cells were found to detach themselves from the surfaces at 20 
      degrees C. The efficiency of thermally-induced cell detachment increased with
      increasing the grafted amount of PIPAAm and the diameter of bead. An efficient
      cell proliferation on bead surfaces in stirred suspension culture and subsequent
      thermally-induced cell detachment were achieved by the precise regulation of both
      the grafted amount of PIPAAm and diameter of bead. The temperature-responsive
      microcarriers exhibiting temperature-dependent cell adhesion and detachment will
      be an attractive candidate for the large-scale cell culture of therapeutic cells.

PMID- 22364729
TI  - Nanoparticle uptake and gene transfer efficiency for MSCs on chitosan and
      chitosan-hyaluronan substrates.
AB  - Nanoparticles (NPs) are usually surface modified to increase endocytosis for
      applications in cellular imaging and gene delivery. The influence of cell culture
      substrates on endocytosis remains relatively unexplored. This study investigated
      the substrate-mediated effects on the uptake of NPs by mesenchymal stem cells
      (MSCs). Two types of NPs were employed, negatively charged paramagnetic iron
      oxide (Fe(3)O(4)) NPs (~5 nm) and bare plasmid DNA pTRE-Tight-DsRED2 (3.3 kb, ~5
      nm), each of which were poorly endocytosed by the adipose-derived MSCs grown on
      tissue culture polystyrene (TCPS). When cells were cultured on chitosan or
      hyaluronan-modified chitosan (chitosan-HA) membranes, significant increases (>5
      fold) in the intracellular uptake of Fe(3)O(4) NPs as well as transfectability of
      plasmid DNA were demonstrated. The enhancement in transgene expression was more
      pronounced than that using the transfection agent. The beneficial effects were
      not caused by elevated proliferation or a change in the differentiation state of
      interacting MSCs. On chitosan and chitosan-HA, cells moved fast and formed
      spheroids. The cytoskeletal arrangement associated with the up-regulated RhoA
      activity during spheroid formation may have accounted for the increased
      endocytosis. Using different inhibitors, the endocytosis pathways were further
      clarified. Both Fe(3)O(4) NPs and plasmid DNA were taken up primarily by clathrin
      mediated endocytosis on chitosan (~50%). The caveolae-mediated endocytosis on
      chitosan-HA was more evident (~30-40%) than that on chitosan (<25%). For plasmid
      DNA but not Fe(3)O(4) NPs, macropinocytosis also occurred on both substrates.
      Chitosan and chitosan-HA as cell culture substrates may activate different
      endocytic pathways of MSCs to increase NP internalization or plasmid
      transfection. The substrate-mediated endocytosis described here may represent a
      new and potentially attractive approach to facilitate stem cell labeling or to
      improve gene delivery efficiency without altering cell viability and
      differentiation.

PMID- 22364730
TI  - Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and
      polyethylene particle-associated bone loss.
AB  - Particle-associated periprosthetic osteolysis remains a major issue in joint
      replacement. Ongoing bone loss resulting from wear particle-induced inflammation
      is accompanied by continued attempts at bone repair. Previously we showed that
      mesenchymal stem cells (MSCs) are recruited systemically to bone exposed to
      continuous infusion of ultra high molecular weight polyethylene (UHMWPE)
      particles. The chemokine-receptor axis that mediates this process is unknown. We
      tested two hypotheses: (1) the CCR1 receptor mediates the systemic recruitment of
      MSCs to UHMWPE particles and (2) recruited MSCs are able to differentiate into
      functional mature osteoblasts and decrease particle-associated bone loss. Nude
      mice were allocated randomly to four groups. UHMWPE particles were continuously
      infused into the femoral shaft using a micro-pump. Genetically modified murine
      wild type reporter MSCs were injected systemically via the left ventricle. Non
      invasive imaging was used to assay MSC migration and bone mineral density.
      Bioluminescence and immunohistochemistry confirmed the chemotaxis of reporter
      cells and their differentiation into mature osteoblasts in the presence of
      infused particles. Injection of a CCR1 antagonist decreased reporter cell
      recruitment to the UHMWPE particle infusion site and increased osteolysis. CCR1
      appears to be a critical receptor for chemotaxis of MSCs in the presence of
      UHMWPE particles. Interference with CCR1 exacerbates particle-induced bone loss.

PMID- 22364731
TI  - Is there a general autoantibody signature for cancer?
AB  - BACKGROUND: There is longstanding evidence for the diagnostic potential of single
      autoantibodies for cancer and other diseases and more recently for the potential
      of complex autoantibody signatures. Here we address the question whether cancer
      specific signatures exist. METHODS: We analysed our autoantibody screening data
      both newly and previously generated using a single array platform with 1827
      identified immunogenic clones. These clones were tested for their reactivity
      against a total of 428 human sera including 191 sera of patients with different
      cancer entities, 60 sera of healthy individuals and 177 sera of patients with non
      cancer diseases by using bioinformatics approaches. RESULTS: Principal Component
      Analysis and hierarchical clustering revealed significant differences between the
      three cohorts. Evaluating the autoantibody reactivities in the three groups using
      Support Vector Machines, we were able to separate cancer sera from normal sera
      with an accuracy of 94.08%. A pathway analysis that was based on antigens with an
      increased reactivity in patients' sera as compared to controls indicated
      glycolysis as central pathway. The separation between cancer and non-cancer
      disease sera was possible with an accuracy of only 69.58%, which is still
      significantly higher than by random classification. CONCLUSION: As for single
      autoantigens, we show that proteins that are frequently reactive with cancer sera
      are also frequently reactive with non-cancer sera. While these results underline
      the potential of autoantibody signatures for cancer diagnosis, they also caution
      to premature claim specificity of a signature.

PMID- 22364732
TI  - Salvage radiotherapy: a plea for dose-escalation with intensity-modulated
      radiotherapy.

PMID- 22364733
TI  - Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously
      treated with a platinum-gemcitabine regimen.
AB  - BACKGROUND: Gemcitabine plus cisplatinum was shown to exert comparable activity
      and a different toxicity profile when compared to the methotrexate, vinblastine,
      doxorubicin, cisplatinum (MVAC) regimen in patients with advanced bladder cancer.
      Accelerated MVAC (aMVAC, the four drugs being administered every 2 weeks with
      granulocyte colony-stimulating factor (G-CSF)) is better tolerated than
      conventional MVAC, with a trend for improved activity. There is no standard of
      care after failure of gemcitabine-platinum (GP) chemotherapy. Our aim was to
      assess the activity and toxicity of accelerated MVAC as second-line treatment.
      METHODS: We reviewed data from patients previously treated with GP who had
      received aMVAC at two institutions at the time of disease progression. RESULTS:
      Forty-five patients received aMVAC after GP: 18 (40%) and 27 (60%) had received
      GP in the adjuvant and the metastatic settings, respectively. The median time to
      progression (TTP) after first-line GP was 9.3 months. The response rate for aMVAC
      was 61%, including 4/38 (10%) complete responses. Median time to progression and
      median overall survival (OS) were 5.8 and 14.2 months, respectively. Median TTP
      and OS were 9.6 and 16.5 months when GP was used in the adjuvant setting and 4.4
      and 5.7 months when GP was used in the metastatic setting. Grade 3-4 toxicities
      were observed in 31 patients (69%), including four sepsis-related deaths.
      CONCLUSION: aMVAC exerts clinical activity after previous treatment with GP,
      especially when GP was used in the adjuvant setting. aMVAC should however be
      administered with caution due to toxicity.

PMID- 22364734
TI  - Intermittent hypoxia and systemic leptin administration induces pSTAT3 and
      Fos/Fra-1 in the carotid body.
AB  - Glomus cells within the carotid body are known to respond to hypoxic stimuli.
      Recently, these cells have been shown to express the long form of the leptin
      receptor (Ob-Rb). However, whether these glomus cells expressing the Ob-Rb are
      activated by hypoxic stimuli is not known. Therefore, in this study we
      investigated whether intermittent hypoxia (IH) or changes in circulating levels
      of leptin induced phosphorylated signal transducer and activator of transcription
      3 (pSTAT3), the immediate early gene c-fos protein, or fos-related antigen-1
      protein (Fra-1) within carotid body glomus cells that expressed the Ob-Rb, and
      within neurons of the petrosal (PG) and nodose (NG) ganglia. Rats were subjected
      to IH (120 s normoxia, 80s hypoxia for 8h) or normoxia (8h), or intravenous
      injections of leptin (50 or 200 ng/0.1 mL) or the vehicle saline. Plasma leptin
      levels were measured in animals exposed to IH and normoxia. Exposure to 8h of IH
      increased plasma leptin levels greater than 2-fold compared to normoxic controls.
      Animals were then perfused with Zamboni's fixative, and the region of the carotid
      bifurcation containing the carotid body and PG/NG complex was removed, paraffin
      embedded and sectioned at 6 MUm for immunohistochemical processing. Carotid body
      glomus cells were identified by their expression of tyrosine hydroxylase
      immunoreactivity. These glomus cells also expressed the OB-Rb and were found to
      express pSTAT3-, fos-, and Fra-1-like immunoreactivity in response to both IH and
      systemic leptin injections. IH and leptin injections also increased fos and Fra-1
      like expression in the PG, NG and jugular ganglion. Taken together, these data
      suggest IH alters circulating leptin which in turn activates directly carotid
      body glomus cells to exert a modulatory effect on the peripheral chemoreceptor
      reflex.

PMID- 22364735
TI  - Reading skill and neural processing accuracy improvement after a 3-hour
      intervention in preschoolers with difficulties in reading-related skills.
AB  - This study aimed at determining whether an intervention game developed for
      strengthening phonological awareness has a remediating effect on reading skills
      and central auditory processing in 6-year-old preschool children with
      difficulties in reading-related skills. After a 3-hour training only, these
      children made a greater progress in reading-related skills than did their matched
      controls who did mathematical exercises following comparable training format.
      Furthermore, the results suggest that this brief intervention might be beneficial
      in modulating the neural basis of phonetic discrimination as an enhanced speech
      elicited mismatch negativity (MMN) was seen in the intervention group, indicating
      improved cortical discrimination accuracy. Moreover, the amplitude increase of
      the vowel-elicited MMN significantly correlated with the improvement in some of
      the reading-skill related test scores. The results, albeit obtained with a
      relatively small sample, are encouraging, suggesting that reading-related skills
      can be improved even by a very short intervention and that the training effects
      are reflected in brain activity. However, studies with larger samples and
      different subgroups of children are needed to confirm the present results and to
      determine how children with different dyslexia subtypes benefit from the
      intervention.

PMID- 22364736
TI  - Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its
      anxiolytic-like action.
AB  - The aim of the study is to determine the acute toxicity and anxiolytic-like
      effects of a mixture of cis and trans of (+)-limonene epoxide in animal models of
      anxiety. After acute treatment with (+)-limonene epoxide at doses of 25, 50 and
      75 mg/kg (i.p.) no mortality was noted during 14 days of observation. In general,
      behavior, food and water consumption showed no significant changes. In open field
      test, (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg, after intraperitoneal
      administration, significantly decreased the number of crossings, grooming and
      rearing (p<0.001). All these effects were reversed by the pre-treatment with
      flumazenil (25 mg/kg, i.p.), similar to those observed with diazepam used as a
      positive standard. In the elevated-plus-maze test, (+)-limonene epoxide increased
      the time of permanence and the number of entrances in the open arms. All these
      effects were reversed by flumazenil, an antagonist of benzodiazepine receptors.
      In addition, (+)-limonene epoxide (75 mg/kg) also produced a significant
      inhibition of the motor coordination (p<0.01), that was reversed by flumazenil.
      In conclusion, the present work evidenced sedative and anxiolytic-like effects of
      (+)-limonene epoxide, which might involve an action on benzodiazepine-type
      receptors. These results indicate that the properties of (+)-limonene epoxide
      should be more thoroughly examined in order to achieve newer tools for management
      and/or treatment of central nervous system diseases and anxiolytic-like effects.
      The LD50 obtained for the acute toxicity studies using intraperitoneal route of
      administration was 4.0 g/kg. These findings suggest that acute administration of
      the (+)-limonene epoxide exerts an anxiolytic-like effect on mice, and it could
      serve as a new approach for the treatment anxiety, since it practically does not
      produce toxic effects.

PMID- 22364737
TI  - Hijacking hebb: noninvasive methods to probe plasticity in psychiatric disease.

PMID- 22364738
TI  - Impaired visual cortical plasticity in schizophrenia.
AB  - BACKGROUND: Impaired cortical plasticity may be part of the core pathophysiology
      of schizophrenia (SZ). Long-term potentiation is a form of neuroplasticity that
      has been recently demonstrated in humans by showing that repetitive visual
      stimulation produces lasting enhancement of visual evoked potentials (VEP). Using
      this paradigm, we examined whether visual cortical plasticity is impaired in SZ.
      METHODS: Electroencephalographic data were recorded from 19 SZ and 22 healthy
      control (HC) subjects during a visual long-term potentiation paradigm. Visual
      evoked potentials were elicited by standard visual stimuli (~.83 Hz, 2-minute
      blocks) at baseline and at 2, 4, and 20 minutes following exposure to visual high
      frequency stimulation (HFS) (~8.8 Hz, 2 minutes) designed to induce VEP
      potentiation. To ensure attentiveness during VEP assessments, subjects responded
      with a button press to infrequent (10%) target stimuli. Visual evoked potentials
      were subjected to principal components analysis. Two negative-voltage components
      prominent over occipital-parietal electrode sites were evident at 92 msec (C1)
      and at 146 msec (N1b). Changes in C1 and N1b component scores from baseline to
      the post-HFS assessments were compared between groups. RESULTS: High-frequency
      stimulation produced sustained potentiation of visual C1 and N1b in HCs but not
      in SZs. The HCs and SZs had comparable HFS-driven electroencephalographic visual
      steady state responses. However, greater visual steady state responses to the HFS
      predicted greater N1b potentiation in HCs but not in SZs. Schizophrenia patients
      with greater N1b potentiation decreased their reaction times to target stimuli.
      CONCLUSIONS: Visual cortical plasticity is impaired in schizophrenia, consistent
      with hypothesized deficits in N-methyl-D-aspartate receptor function.

PMID- 22364740
TI  - The evolving placenta: convergent evolution of variations in the
      endotheliochorial relationship.
AB  - Endotheliochorial placentas occur in orders from all four major clades of
      eutherian mammal. Species with this type of placenta include one of the smallest
      (pygmy shrew) and largest (African elephant) land mammals. The endotheliochorial
      placenta as a definitive form has an interhemal area consisting of maternal
      endothelium, interstitial lamina, trophoblast, individual or conjoint basal
      laminas, and fetal endothelium. We commonly think of such placentas as having
      hypertrophied maternal endothelium with abundant rough endoplasmic reticulum
      (rER), and as having hemophagous regions. Considering them as a whole, the
      trophoblast may be syncytial or cellular, fenestrated or nonfenestrated, and
      there may or may not be hemophagous regions. Variations also appear in the extent
      of hypertrophy of the maternal endothelium and in the abundance of rER in these
      cells. This combination of traits and a few other features produces many
      morphological variants. In addition to endotheliochorial as a definitive
      condition, a transitory endotheliochorial condition may appear in the course of
      forming a hemochorial placenta. In some emballonurid bats the early
      endotheliochorial placenta has two layers of trophoblast, but the definitive
      placenta lacks an outer syncytial trophoblast layer. In mollosid bats a well
      developed endotheliochorial placenta is present for a short time even after a
      definitive hemochorial placenta has developed in a different region. It is
      concluded that the endotheliochorial placenta is more widespread and diversified
      than originally thought, with the variant with cellular trophoblast in particular
      appearing in several species studied recently.

PMID- 22364739
TI  - COMT Val(158)Met genotype determines the direction of cognitive effects produced
      by catechol-O-methyltransferase inhibition.
AB  - BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT
      Val(158)Met polymorphism influences its activity, and multiple neural correlates
      of this genotype on dopaminergic phenotypes, especially working memory, have been
      reported. COMT activity can also be regulated pharmacologically by COMT
      inhibitors. The inverted-U relationship between cortical dopamine signaling and
      working memory predicts that the effects of COMT inhibition will differ according
      to COMT genotype. METHODS: Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT
      Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant
      COMT inhibitor tolcapone or placebo in a randomized, double-blind, between
      subjects design. They completed the N-back task of working memory and a gambling
      task. RESULTS: In the placebo group, Met-COMT subjects outperformed Val-COMT
      subjects on the 2- back, and they were more risk averse. Tolcapone had opposite
      effects in the two genotype groups: it worsened N-back performance in Met-COMT
      subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects
      less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed
      the baseline genotype differences. CONCLUSIONS: Depending on genotype, COMT
      inhibition can enhance or impair working memory and increase or decrease risky
      decision making. To our knowledge, the data are the clearest demonstration to
      date that the direction of effect of a drug can be influenced by a polymorphism
      in its target gene. The results support the inverted-U model of dopamine
      function. The findings are of translational relevance, because COMT inhibitors
      are used in the adjunctive treatment of Parkinson's disease and are under
      evaluation in schizophrenia and other disorders.

PMID- 22364741
TI  - TOR signaling regulates ribosome and tRNA synthesis via LAMMER/Clk and GSK-3
      family kinases.
AB  - Target of rapamycin (TOR)-dependent signaling and the control of cell growth is
      deregulated in many cancers. However, the signaling molecules downstream of TOR
      that coordinately regulate the synthesis of ribosomes and tRNAs are not well
      defined. Here, we show in yeast that conserved kinases of the LAMMER/Cdc-like and
      GSK-3 families function downstream of TOR complex 1 to repress ribosome and tRNA
      synthesis in response to nutrient limitation and other types of cellular stress.
      As a part of this response, we found that the LAMMER kinase Kns1 is
      differentially expressed and hyperphosphorylated and accumulates in the nucleus
      after rapamycin treatment, whereupon it primes the phosphorylation of the RNA
      polymerase III subunit Rpc53 by a specific GSK-3 family member, Mck1. In
      cooperation with another polymerase subunit, Rpc11, this phosphorylation of Rpc53
      modifies the function of the enzyme and together with dephosphorylation of the
      Maf1 repressor inhibits the growth-promoting activity of RNA polymerase III
      transcription.

PMID- 22364743
TI  - Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium
      channel blocker in human prostate cancer xenografts.
AB  - Voltage-gated sodium channels are known to be expressed in neurons and other
      excitable cells. Recently, voltage-gated sodium channels have been found to be
      expressed in human prostate cancer cells. alpha-Hydroxy-alpha-phenylamides are a
      new class of small molecules that have demonstrated potent inhibition of voltage
      gated sodium channels. The hydroxyamide motif, an isostere of a hydantoin ring,
      provides an active scaffold from which several potent racemic sodium channel
      blockers have been derived. With little known about chiral preferences, the
      development of chiral syntheses to obtain each pure enantiomer for evaluation as
      sodium channel blockers is important. Using Seebach and Frater's chiral template,
      cyclocondensation of (R)-3-chloromandelic acid with pivaldehyde furnished both
      the cis- and trans-2,5-disubsituted dioxolanones. Using this chiral template, we
      synthesized both enantiomers of 2-(3-chlorophenyl)-2-hydroxynonanamide, and
      evaluated their ability to functionally inhibit hNa(v) isoforms, human prostate
      cancer cells and xenograft. Enantiomers of lead demonstrated significant ability
      to reduce prostate cancer in vivo.

PMID- 22364744
TI  - Efficient synthesis and biological evaluation of proximicins A, B and C.
AB  - A quick and efficient synthesis and the biological evaluation of promising
      antitumor-antibiotics proximicins A, B and C are reported. The characteristic
      repetitive unit of these molecules, the methyl 4-Boc-aminofuran-2-carboxylate 15,
      was prepared in three synthetic steps in good yield using an optimised copper
      catalysed amidation method. The proximicins were evaluated for their antitumor
      activity using cellular methods. Proximicin B induced apoptosis in both Hodgkin's
      lymphoma and T-cell leukemia cell lines and proximicin C exhibited significantly
      high cytotoxicity against glioblastoma and breast carcinoma cells. The
      proximicins were also screened against Escherichia coli, Enterococcus faecalis
      and several strains of methicillin-and multidrug-resistant Staphylococcus aureus.
      Proximicin B showed noteworthy activity against antibiotic-resistant Gram
      positive cocci.

PMID- 22364742
TI  - IL6-mediated suppression of miR-200c directs constitutive activation of
      inflammatory signaling circuit driving transformation and tumorigenesis.
AB  - Abnormal inflammatory signaling activation occurs commonly in cancer cells.
      However, how it is initiated and maintained and its roles in early stages of
      tumorigensis are largely unknown. Here, we report that the monocyte-derived MCP-1
      induced transformation of immortal breast epithelial cells is triggered by
      transient activation of MEK/ERK and IKK/NF-kappaB pathways and maintained by
      constitutive activation of a feed-forward inflammatory signaling circuit composed
      of miR-200c, p65, JNK2, HSF1, and IL6. Suppression of miR-200c by IL6
      constitutively activates p65/RelA and JNK2, and the latter phosphorylates and
      activates HSF1. In turn, HSF1 triggers demethylation of the IL6 promoter that
      facilitates the binding of p65 and c-Jun, which together drive constitutive IL6
      transcription. Importantly, this signaling circuit is manifest in human cancer
      cells and in a mouse model of ErbB2-driven breast cancer, where IL6 loss
      significantly impairs tumorigenesis. Therefore, targeting this signaling circuit
      represents an effective therapeutic avenue for breast cancer prevention and
      treatment.

PMID- 22364745
TI  - The synthesis of 2'-methylseleno adenosine and guanosine 5'-triphosphates.
AB  - Modified nucleoside triphosphates (NTPs) represent powerful building blocks to
      generate nucleic acids with novel properties by enzymatic synthesis. We have
      recently demonstrated the access to 2'-SeCH(3)-uridine and 2'-SeCH(3)-cytidine
      derivatized RNAs for applications in RNA crystallography, using the corresponding
      nucleoside triphosphates and distinct mutants of T7 RNA polymerase. In the
      present note, we introduce the chemical synthesis of the novel 2'-methylseleno-2'
      deoxyadenosine and -guanosine 5'-triphosphates (2'-SeCH(3)-ATP and 2'-SeCH(3)
      GTP) that represent further candidates for the enzymatic RNA synthesis with
      engineered RNA polymerases.

PMID- 22364746
TI  - Synthesis and biological evaluation of 4beta-sulphonamido and 4beta-[(4'
      sulphonamido)benzamide]podophyllotoxins as DNA topoisomerase-IIalpha and
      apoptosis inducing agents.
AB  - A series of new 4beta-sulphonamido and 4beta-[(4'-sulphonamido)benzamide]
      conjugates of podophyllotoxin (11a-j and 15a-g) were synthesized and evaluated
      for anticancer activity against six human cancer cell lines and found to be more
      potent than etoposide. Some of the compounds 11b, 11d and 11e that showed
      significant antiproliferative activity in Colo-205 cells, were superior to
      etoposide. The flow cytometric analysis indicates that these compounds (11b, 11d
      and 11e) showed G2/M cell cycle arrest and among them 11e is the most effective.
      It is observed that this compound (11e) caused both single-strand DNA breaks as
      observed by comet assay as well as double-strand DNA breaks as indicated by gamma
      H2AX. Further 11e showed inhibition of topo-IIalpha as observed from Western blot
      analysis and related studies. Compounds caused activation of ATM as well as Chk1
      protein indicating that the compound caused effective DNA damage. Moreover
      activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein
      suggests that this compound (11e) has apoptotic cell death inducing ability,
      apart from acting as a topo-IIalpha inhibitor.

PMID- 22364747
TI  - Counterfeit drugs: a growing global threat.

PMID- 22364748
TI  - Approval of biosimilars in the USA--dead ringers?

PMID- 22364749
TI  - Social determinants of health: the environmental dimension.

PMID- 22364752
TI  - Azad Khan: prime mover behind NCD programmes in Bangladesh.

PMID- 22364753
TI  - Exhaled nitric oxide as a guide to management of asthma in pregnancy.

PMID- 22364755
TI  - Cost-effectiveness of diagnosis of high blood pressure in primary care.

PMID- 22364756
TI  - Side-effects of roflumilast.

PMID- 22364759
TI  - The good news about cancer in developing countries--pathology answers the call.

PMID- 22364760
TI  - Thrombocytopenia in a nutshell.

PMID- 22364761
TI  - NMR relaxometry as a versatile tool to study Li ion dynamics in potential battery
      materials.
AB  - NMR spin relaxometry is known to be a powerful tool for the investigation of
      Li(+) dynamics in (non-paramagnetic) crystalline and amorphous solids. As long as
      significant structural changes are absent in a relatively wide temperature range,
      with NMR spin-lattice (as well as spin-spin) relaxation measurements information
      on Li self-diffusion parameters such as jump rates and activation energies are
      accessible. Diffusion-induced NMR relaxation rates are governed by a motional
      correlation function describing the ion dynamics present. Besides the mean
      correlation rate of the dynamic process, the motional correlation function (i)
      reflects deviations from random motion (so-called correlation effects) and (ii)
      gives insights into the dimensionality of the hopping process. In favorable
      cases, i.e., when temperature- and frequency-dependent NMR relaxation rates are
      available over a large dynamic range, NMR spin relaxometry is able to provide a
      comprehensive picture of the relevant Li dynamic processes. In the present
      contribution, we exemplarily present two recent variable-temperature (7)Li NMR
      spin-lattice relaxation studies focussing on Li(+) dynamics in crystalline ion
      conductors which are of relevance for battery applications, viz. Li(7)
      La(3)Zr(2)O(12) and Li(12)Si(7).

PMID- 22364762
TI  - Social support for self-management behaviors among people with epilepsy: a
      content analysis of the WebEase program.
AB  - Social support is an important component in managing epilepsy; however little is
      known about support provided to people with epilepsy. This study examined whom
      people with epilepsy identify as supportive, and how those individuals support
      people with epilepsy's self-management efforts. Data come from the WebEase
      project, an effective online epilepsy self-management program. People with
      epilepsy who participated in the pilot (n=35) and efficacy trials (n=118) were
      included. A content analysis was conducted on responses to open-ended questions
      related to support. The majority of participants provided information about their
      supporters. The number of support providers ranged from 0 to 6, with about 12%
      indicating no support. Parents and significant others were most commonly listed
      as supporters. Support providers mainly offer emotional and instrumental support,
      reminders and aid for taking medication, and support for self-management
      strategies. These results could be useful for interventions aimed at bolstering
      support in order to improve self-management.

PMID- 22364763
TI  - Effects of experimental osteoporosis and low calcium intake on postextraction
      sockets of rats.
AB  - This study analysed the initial effects of the combination of oestrogen
      deficiency with a calcium-deficient diet on alveolar bone repair. Sixty-three 3
      month-old female rats were either ovariectomized (OVX, n = 42) or sham-operated
      (SHAM, n = 21). Among the 42 ovariectomized rats, 21 received standard commercial
      food (OVX) and 21 received food with low calcium content (ESP). The mandibular
      first molars were extracted bilaterally 15 days after ovariectomy or sham
      surgery. The rats were weighed and killed at 7, 21 and 45 days after tooth
      extraction. The results were evaluated by descriptive microscopic analysis,
      histomorphometry of the trabecular and osteoid volume and mast cell counts.
      Analysis of the results indicated that trabecular volume and mast cell counts
      increased significantly over time, while osteoid volume decreased over time.
      Comparisons between the SHAM and OVX groups demonstrated no statistical
      differences, while comparison between the OVX and ESP groups indicated
      differences in trabecular volume and the number of mast cells. The data suggest
      that hormonal deficiency does not delay alveolar bone repair in OVX rats;
      however, oestrogen deficiency associated with calcium deficiency can lead to bone
      resorption through the activation of mast cells.

PMID- 22364764
TI  - Advances in high density lipoprotein formation and metabolism: a tribute to John
      F. Oram (1945-2010).

PMID- 22364765
TI  - [Severe hyperthermia and neurological disorders following prostaglandin treatment
      for uterine atonia after caesarean section].
AB  - Uterine atony is the most frequent cause of post-partum haemorrhage. In France,
      the management is based on early administration of oxytocic agents and
      prostaglandin analogues (sulprostone-Nalador(r)). We report the case of a 30-year
      old woman who presented soon after administration of sulprostone, a severe
      hyperthermia with neurological disorders. A complete reversibility was observed a
      few hours after discontinuation of sulprostone administration. Other causes were
      eliminated by biological and radiological findings.

PMID- 22364766
TI  - [History of acute kidney injury, the early development of hemodialysis in
      France].
AB  - From the end of the 19th century to the 1950s, from mechanisms of disease and
      pathology to the first success of hemodialysis, the author depicts the history of
      acute kidney injury. These remarkable improvements of modern medicine led
      concurrently to the spread of hemodialysis for the replacement of end-stage renal
      disease.

PMID- 22364767
TI  - The effect of chlorotrimethylsilane on bonding of nano hydroxyapatite with a
      chitosan-polyacrylamide matrix.
AB  - Stimuli sensitive biodegradable polymers have important applications in the
      fields of drug delivery and tissue engineering. In this study, biodegradable
      composite films of chitosan-polyacrylamide-nano hydroxyapatite (Cs-PAAm-nHA) with
      different concentrations of Chlorotrimethylsilane (CTMS) were fabricated and
      characterized using Fourier transform infrared (FTIR) spectroscopy. FTIR and XRD
      results suggested that CTMS functioned to couple nHA with the Cs-PAAm polymer
      matrix. The swelling study indicated that the formation of numerous CTMS based
      inter-chain bridges and pores facilitated water absorption and swelling. Hence,
      incorporation of CTMS into Cs-PAAm-nHA composites not only improved their
      stability but also controlled the degradation of the composites, which are
      important for drug delivery applications.

PMID- 22364768
TI  - Nerve root herniation into a calcified pseudomeningocele after lumbar
      laminectomy.

PMID- 22364769
TI  - Cervical pseudarthrosis and lumbar fusion mass.

PMID- 22364770
TI  - Anaerobic digestibility of algal bioethanol residue.
AB  - The aim of this work was to investigate anaerobic digestibility of algal
      bioethanol residue from saccharification and fermentation processes. A series of
      batch anaerobic digestion tests using saccharification and fermentation residue
      showed that the maximum methane yields of saccharification residue and
      fermentation residue were 239 L/kg VS (Volatile Solids) and 283 L/kg VS (Volatile
      Solids), respectively. Energy recovered by anaerobic digestion of the residue was
      2.24 times higher than that from the ethanol produced in the main process. 5-HMF
      (5-hydroxymethylfurfural), a saccharification byproduct, could retard
      methanogenesis at over 3g/L however, the inhibition was prevented by increasing
      cell biomass concentration. Anaerobic digestion of residue has the potential to
      enhance bioenergy recovery and environmental sustainability of algal bioethanol
      production.

PMID- 22364771
TI  - Capacitive deionization coupled with microbial fuel cells to desalinate low
      concentration salt water.
AB  - A new technology (CDI-MFC) that combined capacitive deionization (CDI) and
      microbial fuel cell (MFC) was developed to treat low-concentration salt water
      with NaCl concentration of 60mg/L. The water desalination rate was 35.6mg/(Lh),
      meanwhile the charge efficiency was 21.8%. Two desorption modes were
      investigated: discharging (DC) mode and short circuit (SC) mode. The desalination
      rate in the DC mode was 200.6+/-3.1mg/(Lh), 47.8% higher than that in the SC mode
      [135.7+/-15.3mg/(Lh)]. The average current in the DC mode was also much higher
      than that of the SC mode. The energy stored in the CDI cell has been reused to
      enhance the electron production of MFC by the discharging desorption mode (DC
      mode), which offers an approach to recover the electrostatic energy in the CDI
      cell.

PMID- 22364772
TI  - Evolution of the chloroplast genome in photosynthetic euglenoids: a comparison of
      Eutreptia viridis and Euglena gracilis (Euglenophyta).
AB  - The chloroplast genome of Eutreptia viridis Perty, a basal taxon in the
      photosynthetic euglenoid lineage, was sequenced and compared with that of Euglena
      gracilis Ehrenberg, a crown species. Several common gene clusters were identified
      and gene order, conservation, and sequence similarity was assessed through
      comparisons with Euglena gracilis. Significant gene rearrangements were present
      between Eutreptia viridis and Euglena gracilis chloroplast genomes. In addition,
      major expansion has occurred in the Euglena gracilis chloroplast accounting for
      its larger size. However, the key chloroplast genes are present and differ only
      in the absence of psaM and roaA in Eutreptia viridis, and psaI in Euglena
      gracilis, suggesting a high level of gene conservation within the euglenoid
      lineage. Further comparisons with the plastid genomes of closely related green
      algal taxa have provided additional support for the hypothesis that a Pyramimonas
      like alga was the euglenoid chloroplast donor via secondary endosymbiosis.

PMID- 22364773
TI  - Multigene phylogenies of diverse Carpediemonas-like organisms identify the
      closest relatives of 'amitochondriate' diplomonads and retortamonads.
AB  - Diplomonads, retortamonads, and "Carpediemonas-like" organisms (CLOs) are a
      monophyletic group of protists that are microaerophilic/anaerobic and lack
      typical mitochondria. Most diplomonads and retortamonads are parasites, and the
      pathogen Giardia intestinalis is known to possess reduced mitochondrion-related
      organelles (mitosomes) that do not synthesize ATP. By contrast, free-living CLOs
      have larger organelles that superficially resemble some hydrogenosomes,
      organelles that in other protists are known to synthesize ATP anaerobically. This
      group represents an excellent system for studying the evolution of parasitism and
      anaerobic, mitochondrion-related organelles. Understanding these evolutionary
      transitions requires a well-resolved phylogeny of diplomonads, retortamonads and
      CLOs. Unfortunately, until now the deep relationships amongst these taxa were
      unresolved due to limited data for almost all of the CLO lineages. To address
      this, we assembled a dataset of up to six protein-coding genes that includes
      representatives from all six CLO lineages, and complements existing rRNA
      datasets. Multigene phylogenetic analyses place CLOs as well as the retortamonad
      Chilomastix as a paraphyletic basal assemblage to the lineage comprising
      diplomonads and the retortamonad Retortamonas. In particular, the CLO Dysnectes
      was shown to be the closest relative of the diplomonads + Retortamonas clade,
      with strong support. This phylogeny is consistent with a drastic degeneration of
      mitochondrion-related organelles during the evolution from a free-living organism
      resembling extant CLOs to a probable parasite/commensal common ancestor of
      diplomonads and Retortamonas.

PMID- 22364774
TI  - The role of mitochondrial Ca(2+) and NAD(P)H in the control of aldosterone
      secretion.
AB  - The mineralocorticoid hormone aldosterone is synthesized in the zona glomerulosa
      of the adrenal cortex. Glomerulosa cells respond to the physiological stimuli,
      elevated extracellular [K(+)] and angiotensin II, with an intracellular Ca(2+)
      signal. Cytosolic Ca(2+) facilitates the transport of the steroid-precursor
      cholesterol to mitochondria and, after a few hours, it also induces the
      transcription of aldosterone synthase. Therefore, the cytosolic Ca(2+) signal is
      regarded as the most important short and long-term mediator of aldosterone
      secretion. However, cytosolic Ca(2+) is also taken up by mitochondria and, in
      turn, the mitochondrial Ca(2+) response activates mitochondrial dehydrogenases
      resulting in stimulation of respiration and increase in reduced pyridine
      nucleotides. Since both cholesterol side-chain cleavage and all of the
      hydroxylation steps of steroid synthesis require NADPH as a cofactor, the
      importance of cytosolic Ca(2+) - mitochondrial Ca(2+) coupling and of appropriate
      NADPH supply in respect to hormone production can be assumed. However, the
      importance of the mitochondrial factors has been neglected so far. Here, after
      summarizing earlier findings we provide new results obtained through modifying
      mitochondrial Ca(2+) uptake by knocking down p38 MAPK or OPA1 and overexpressing
      S100G, supporting the notion that mitochondrial Ca(2+) and reduced pyridine
      nucleotides are facilitating factors for both basal and stimulated steroid
      production.

PMID- 22364775
TI  - Effects of rapamycin-induced oligomerization of parvalbumin, Stim1 and Orai1 in
      puncta formation.
AB  - Elevations of cytosolic Ca2+ from the endoplasmic reticulum (ER) regulate a
      diverse range of cellular processes. When these luminal stores become depleted,
      the transmembrane ER protein Stim1 oligomerizes and translocates within the ER
      membrane to puncta junctions to couple with Orai1 channels, activating store
      operated calcium entry (SOCE). Stim1 oligomerization and puncta formation have
      generally been associated with its luminal domains, however, studies have
      implicated that the cytoplasmic domains may contribute to this oligomerization.
      Studies have also suggested that intermediate or regulating elements may be
      required to fine-tune puncta formation and activation of SOCE. Here we made
      fusion proteins of Stim1 and Orai1 with FRB and FKBP12 domains that associate in
      the presence of rapamycin. Rapamycin-induced coupling of Stim1 to Stim1, Orai1 to
      Orai1 and Stim1 to Orai1 was found to be insufficient for puncta formation.
      Rapamycin was then used to recruit the cytosolic Ca2+ buffer protein parvalbumin
      (Pav) to Stim1 in order to buffer the local cytosolic Ca2+ near the ER membrane.
      Interestingly, Pav buffering near the ER caused puncta formation that was
      indistinguishable from those caused by thapsigargin. Our results suggest that
      Stim1 oligomerization and puncta formation may be additionally regulated either
      by local Ca2+ levels near the ER membrane or by as yet unidentified Ca2+
      dependent proteins interacting with the cytoplasmic domains of Stim1.

PMID- 22364776
TI  - Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and
      tobacco withdrawal symptoms in adult smokers with ADHD.
AB  - BACKGROUND: Tobacco withdrawal symptoms may be confounded with attention
      deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD.
      OBJECTIVE: (1) To assess overlap between ADHD symptoms and tobacco/nicotine
      withdrawal symptoms and craving; (2) to assess the relationship between craving
      or withdrawal symptoms and the effect of osmotic-release oral system
      methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of
      ADHD symptoms, craving, and withdrawal symptoms with abstinence. METHODS:
      Secondary analysis of a randomized, placebo controlled smoking cessation trial
      assessing the efficacy of OROS-MPH taken in addition to nicotine patch among
      individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were
      assessed at baseline and 2, 4 and 6 weeks after a target quit day. RESULTS:
      Withdrawal symptoms and craving showed limited and modest overlap with ADHD
      symptoms prior to abstinence but more extensive and stronger correlation after
      quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was
      attenuated by controlling for withdrawal symptoms, but not by craving. Craving,
      but not ADHD symptoms and withdrawal symptoms, was associated with abstinence
      during the trial. CONCLUSION: When treating smokers with ADHD (1) craving, rather
      than tobacco withdrawal symptoms or ADHD symptoms may be the more effective
      therapeutic smoking cessation targets; (2) careful distinction of craving,
      withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is
      needed.

PMID- 22364777
TI  - The Washington circle engagement performance measures' association with
      adolescent treatment outcomes.
AB  - BACKGROUND: For adolescents, substance use disorder (SUD) treatment outcomes
      (e.g., abstinence, problematic behaviors) often cannot be measured soon enough to
      influence treatment trajectory. Although process measures (e.g., treatment
      engagement) can play an important role, it is essential to demonstrate their
      association with outcomes. This study explored the extent to which engagement in
      outpatient treatment was associated with outcomes and whether
      demographic/clinical characteristics moderated these relationships. METHODS: This
      is a prospective study of adolescents (N=1491) who received outpatient treatment
      for SUDs at one of 28 treatment sites taking part in a national evidence-based
      practice implementation initiative. Information from the Global Appraisal of
      Individual Needs interviews at intake and six-month follow-up, as well as
      encounter data, were used. Adjusted hierarchical logistic models were used to
      estimate effects of engagement on six-month outcomes. RESULTS: Sixty-one percent
      of adolescents engaged in outpatient treatment. Adolescents engaging in treatment
      had significantly lower likelihoods of reporting any substance use (OR 0.60, 95%
      CI 0.41, 0.87), alcohol use (OR 0.63, 95% CI 0.45, 0.87), heavy alcohol use (OR
      0.53, 95% CI 0.33, 0.86), and marijuana use (OR 0.64, 95% CI 0.45, 0.93). This
      association of engagement with abstinence outcomes was not limited to any
      particular group. Treatment engagement, however, was not associated with
      adolescents' self-report of illegal activity or trouble controlling behavior at
      follow-up. CONCLUSION: At the individual level, the Washington Circle engagement
      measure was a predictor of some positive outcomes for adolescents in outpatient
      treatment. Efforts to better engage adolescents in treatment could improve
      quality of care.

PMID- 22364778
TI  - Gait analysis of adults with generalised joint hypermobility.
AB  - BACKGROUND: The majority of adults with Generalised Joint Hypermobility
      experience symptoms such as pain and joint instability, which is likely to
      influence their gait pattern. Accordingly, the purpose of the present project was
      to perform a biomechanical gait analysis on a group of patients with Generalised
      Joint Hypermobility and compare them to a group of healthy subjects. METHODS:
      Seventeen adults clinically classified with Generalised Joint Hypermobility (6
      males and 11 females) and seventeen healthy subjects (9 males and 8 females) were
      included in the project. The subjects walked across three force platforms while
      they were filmed by five video cameras. Net joint moments were calculated in 3D
      by inverse dynamics and peak values were input to statistical analyses. A 3D knee
      joint model was used to calculate bone-on-bone forces. FINDINGS: In the frontal
      plane both the peak knee and hip abductor moments were 13% higher in the patient
      group. In the sagittal plane the peak knee extensor moment was 10% higher for the
      patients and the flexor moment about the knee joint in the middle of stance was
      27% lower for the patients. Increased flexion in the knee joint for the patients
      was also observed. INTERPRETATION: The finding that adults with Generalised Joint
      Hypermobility display higher joint moments during walking in both the frontal and
      the sagittal planes and increased knee joint loadings may explain the pain
      symptoms in the patient group and indicate these subjects are subjected to an
      increased risk of developing osteo-arthritis.

PMID- 22364779
TI  - Extracting plants core genes responding to abiotic stresses by penalized matrix
      decomposition.
AB  - Sparse methods have a significant advantage to reduce the complexity of genes
      expression data and to make them more comprehensible and interpretable. In this
      paper, based on penalized matrix decomposition (PMD), a novel approach is
      proposed to extract plants core genes, i.e., the characteristic gene set,
      responding to abiotic stresses. Core genes can capture the changes of the
      samples. In other words, the features of samples can be caught by the core genes.
      The experimental results show that the proposed PMD-based method is efficient to
      extract the core genes closely related to the abiotic stresses.

PMID- 22364781
TI  - Tako-tsubo cardiomyopathy probably associated with administration of sulprostone
      following cesarean delivery.

PMID- 22364780
TI  - Field assessment of Bt cry1Ah corn pollen on the survival, development and
      behavior of Apis mellifera ligustica.
AB  - Honeybees may be exposed to insecticidal proteins from transgenic plants via
      pollen. An assessment of the impact of such exposures on the honeybee is an
      essential part of the risk assessment process for transgenic Bacillus
      thuringiensis corn. A field trial was conducted to evaluate the effect of
      transgenic Bt cry1Ah corn on the honeybee Apis mellifera ligustica. Colonies of
      honeybees were moved to Bt or non-Bt corn fields during anthesis and then sampled
      to record their survival, development and behavior. No differences in immature
      stages, worker survival, bee body weight, hypopharyngeal gland weight, colony
      performance, foraging activity or olfactory learning abilities were detected
      between colonies that were placed in non-Bt corn fields and those placed in Bt
      corn fields. We conclude that cry1Ah corn carries no risk for the survival,
      development, colony performance or behavior of the honeybee A. mellifera
      ligustica.

PMID- 22364782
TI  - Highly reproducible secondary electron imaging under electron irradiation using
      high-pass energy filtering in low-voltage scanning electron microscopy.
AB  - The reproducibility of contrast in secondary electron (SE) imaging during
      continuous electron irradiation, which caused surface contamination, was
      investigated using SE high-pass energy filtering in low-voltage scanning electron
      microscopy (SEM). According to high-pass energy-filtered imaging, dopant contrast
      in an indium phosphide remained remarkably stable during continuous electron
      irradiation although the contrast in unfiltered SE images decreased rapidly as a
      contamination layer was formed. Charge neutralization and the SE energy
      distributions indicate that the contamination layer induces a positive charge.
      This results in a decrease of low-energy SE emissions and reduced dopant contrast
      in unfiltered SE images. The retention of contrast was also observed in high-pass
      energy-filtered images of a gold surface. These results suggest that this imaging
      method can be widely used when SE intensities decrease under continuous electron
      irradiation in unfiltered SE images. Thus, high-pass energy-filtered SE imaging
      will be of a great assistance for SEM users in the reproducibility of contrast
      such as a quantitative dopant mapping in semiconductors.

PMID- 22364783
TI  - Pemetrexed, oxaliplatin and bevacizumab as first-line treatment in patients with
      stage IV non-small cell lung cancer.
AB  - BACKGROUND: Oxaliplatin has less haematological toxicity than cisplatin and
      carboplatin. The combination of pemetrexed, oxaliplatin and bevacizumab appeared
      well tolerated and active as second- or third-line treatment in a previous phase
      II study. Its role as first-line therapy remains to define. PATIENTS AND METHODS:
      From August 2008 to May 2011, consecutive chemo-naive patients with stage IV non
      squamous non-small cell lung cancer (NSCLC) received pemetrexed 500mg/m(2),
      oxaliplatin 100mg/m(2) and bevacizumab 7.5mg/kg every 3 weeks for 6 cycles, in
      the outpatient setting. Maintenance therapy including pemetrexed and bevacizumab
      was given to patients with non-progressive disease. The primary evaluation
      criterion was safety. Secondary evaluation criteria were response rate,
      progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-eight
      patients (50% males, median age: 55 years, range 38-76) received a total of 199
      cycles (median per patient: 6, range 2-6), plus 98 cycles of maintenance therapy.
      Twenty patients (52.6%) had a PS of 2, and 6 (15.8%) had brain metastases. The
      most frequent toxicities were hypertension (all grades: 42.1%) and peripheral
      neuropathy (grade 2-3: 21.1%). Haematological toxicities included grade 4
      neutropenia, grade 3 anaemia and thrombopenia (5.3% each). Neither febrile
      neutropenia nor arterial thrombo-embolic event occurred. The objective response
      rate was 55.3% (95%CI: 39.5-71.1). The median PFS and OS were 6.2 (95%CI: 5.4
      9.0) and 14.6 (95%CI: 9.8-19.5) months, respectively. CONCLUSIONS: In this single
      centre experience, the combination of pemetrexed, oxaliplatin and bevacizumab was
      well tolerated and had promising activity as first-line therapy in unselected
      patients with stage IV non-squamous NSCLC.

PMID- 22364784
TI  - Determination of Cu/Zn and Fe in human serum of patients with sickle cell anemia
      using radiation synchrotron.
AB  - In this work we analyzed serum samples from patients with Sickle Cell Anemia
      (SCA) using Total Reflection X-Ray Fluorescence using Synchrotron Radiation
      (SRTXRF). The SRTXRF measurements were performed at the X-Ray Fluorescence
      Beamline at the Brazilian National Synchrotron Light Laboratory (LNLS). We
      studied forty-three patients aged 18-50 suffering from SCA and sixty healthy
      volunteers aged 18-60. It was possible to determine the concentrations of the
      following elements: P, S, Cl, K, Ca, Fe, Cu, Zn, Br and Rb. Moreover, there are
      evidences of an association among Fe, Cu, Zn and Cu/Zn in the SCA pathogenesis
      process. The concentrations of Fe and Cu in the serum samples of patients with
      SCA were larger, 120% and 20%, respectively, when compared with the CG. The serum
      level Cu/Zn ratio was significantly higher (60%) in the serum samples from
      patients suffering from SCA than from the CG. Therefore, the Cu/Zn ratio can be
      used as an adjuvant index in enhancement for diagnosis of SCA.

PMID- 22364785
TI  - Molecular dynamics simulation for PBR pebble tracking simulation via a random
      walk approach using Monte Carlo simulation.
AB  - Using a Monte Carlo (MC) simulation, random walks were used for pebble tracking
      in a two-dimensional geometry in the presence of a biased gravity field. We
      investigated the effect of viscosity damping in the presence of random Gaussian
      fluctuations. The particle tracks were generated by Molecular Dynamics (MD)
      simulation for a Pebble Bed Reactor. The MD simulations were conducted in the
      interaction of noncohesive Hertz-Mindlin theory where the random walk MC
      simulation has a correlation with the MD simulation. This treatment can easily be
      extended to include the generation of transient gamma-ray spectra from a single
      pebble that contains a radioactive tracer. Then the inverse analysis thereof
      could be made to determine the uncertainty of the realistic measurement of
      transient positions of that pebble by any given radiation detection system
      designed for that purpose.

PMID- 22364786
TI  - Response tests of a LaCl(3):Ce scintillation detector with low energy prompt
      gamma rays from boron and cadmium.
AB  - The yield of 478 and 558 keV gamma-rays have been measured from water samples
      containing 0.031-0.500 wt. % boron and 0.0625-0.500 wt. % cadmium, respectively,
      using a cylindrical 76 mm * 76 mm (height * diameter) LaCl(3):Ce detector.
      Inspite of interferences between detector-associated and the sample-associated
      prompt gamma rays, the LaCl(3):Ce detector has excellent resolution for the low
      energy prompt gamma-rays. An excellent agreement has been observed between the
      experimental and calculated yield of boron and cadmium prompt gamma ray from
      water samples.

PMID- 22364787
TI  - Quality control methodology and implementation of X-radiation standards beams,
      mammography level, following the standard IEC 61267.
AB  - This study presents the results of the establishment of a quality control program
      developed and applied for the X-ray system of the Calibration Laboratory of IPEN.
      The X-ray standard beams, mammography level, using molybdenum and aluminum as
      additional filtration were established after the application of this quality
      control and the spectrometry of these qualities was made. The reference
      ionization chamber has traceability to the PTB. The radiation qualities RQR-M,
      RQA-M, RQN-M and RQB-M, following the recommendations of the IEC 61267 and the
      IAEA TRS 457 were established.

PMID- 22364788
TI  - Demonstration of enhanced iodine K-edge imaging using an energy-dispersive X-ray
      computed tomography system with a 25 mm/s-scan linear cadmium telluride detector
      and a single comparator.
AB  - An energy-dispersive (ED) X-ray computed tomography (CT) system is useful for
      carrying out monochromatic imaging. To perform enhanced iodine K-edge CT, we
      developed an oscillation linear cadmium telluride (CdTe) detector with a scan
      velocity of 25 mm/s and an energy resolution of 1.2 keV. CT is performed by
      repeated linear scans and rotations of an object. Penetrating X-ray photons from
      the object are detected by the CdTe detector, and event signals of X-ray photons
      are produced using charge-sensitive and shaping amplifiers. The lower photon
      energy is determined by a comparator device, and the maximum photon energy of 60
      keV corresponds to the tube voltage. Rectangular-shaped comparator outputs are
      counted by a counter card. In the ED-CT, tube voltage and current were 60 kV and
      0.30 mA, respectively, and X-ray intensity was 14.8 MUGy/s at 1.0m from the
      source at a tube voltage of 60 kV. Demonstration of enhanced iodine K-edge X-ray
      CT for cancer diagnosis was carried out by selecting photons with energies
      ranging from 34 to 60 keV.

PMID- 22364789
TI  - Outcome of cochlear implantation in children with congenital cytomegalovirus
      infection or GJB2 mutation.
AB  - CONCLUSIONS: Outcomes following cochlear implantation in children with congenital
      cytomegalovirus (CMV) infection were almost equivalent to those of children with
      GJB2 mutation-related sensorineural hearing loss (SNHL). Although our patients
      with developmental disorder showed poor auditory performance and speech and
      language skills after cochlear implantation, SNHL with developmental disorder
      should not be a contraindication for the procedure. OBJECTIVE: Congenital CMV
      infection accounts for approximately 20% of all cases of neonatal hearing loss,
      while the GJB2 mutation accounts for 30-50% of all cases of profound nonsyndromic
      hearing loss. Here, outcomes for auditory behavior and speech and language skills
      were compared in children with congenital CMV infection or GJB2 mutation who
      received cochlear implantation for profound SNHL. METHODS: Five children with
      asymptomatic congenital CMV infection and seven children with GJB2 mutation
      related SNHL, with and without developmental disorder, underwent cochlear
      implantation. Hearing level and speech and language development were evaluated
      post-implantation using IT-MAIS, MUSS, and S-S method. RESULTS: The IT-MAIS and
      MUSS scores of the congenital CMV infection group and the GJB2 mutation group
      continued to increase for 4 years after implantation. The S-S method score in
      both groups gradually increased, although the scores for children with mental
      retardation were low.

PMID- 22364790
TI  - The differences in spiritual health between non-depressed and depressed nurses.
AB  - AIMS AND OBJECTIVES: The aim of this study was to compare the differences in
      spiritual health between depressed and non-depressed nurses. BACKGROUND: Previous
      studies have revealed that spirituality can buffer emotional pressure and
      maintain health, even in cases of depression. Nurses may have a tendency to
      develop depression; however, the relationship between depression and spirituality
      in nurses has been investigated only rarely. DESIGN: A correlational study.
      METHODS: The study was conducted using a convenience sample of 283 nurses who
      worked at a local hospital in northern Taiwan. We used a structured, self
      administered questionnaire to obtain the data. This questionnaire included a
      spiritual health scale, the Beck Depression Inventory and personal data. The
      quantitative data were analysed using the t-test, one-way analysis of variance
      and logistic regression. RESULTS: All the participants were women, and 22.6% of
      the participants were ascertained to have depression. The non-depressed group had
      a higher average score for the different domains of the spiritual health scale
      than the depressed group. When personal and job-related variables were
      controlled, spirituality was a significant explanatory variable for depression.
      CONCLUSIONS: The spiritual health of the non-depressed nurses was better than
      that of the depressed nurses. The result was consistent with the previous studies
      on other populations. RELEVANCE TO CLINICAL PRACTICE: The spiritual health and
      depression of nurses should be paid attention by nursing administrators.
      Spiritual promoting programme in preventing depression should be examined in
      future researches.

PMID- 22364791
TI  - Molecular identification of vaginal fluid by microbial signature.
AB  - The discrimination of body fluids in forensic examinations can play an important
      role in crime scene reconstruction. Conventional methods rely on the detection of
      antigens or enzymatic activity, limiting detection sensitivity and specificity,
      particularly on old forensic samples. Methods based on human RNA analysis are not
      easily applicable to samples exposed to harsh and degrading environments. An
      alternative approach based on the identification of prokaryotic genomes was
      developed. Specific bacterial communities are characteristic typical of different
      human non-sterile body fluids: the molecular characterization of a microbial
      signature, and not the typing of single bacterial species, can effectively lead
      to univocal identification of these fluids. A multiplex real time PCR assay was
      developed using oligonucleotide mixtures targeting genomes specific for a
      selected group of bacteria. Microflora DNA (mfDNA) was extracted from vaginal,
      oral and fecal clinical swabs. In addition forensic samples were processed.
      Vaginal samples showed a strong specific signal for bacteria of the female
      genital tract. Oral samples clearly showed signal for bacteria present in saliva,
      and in fecal samples the main signal was from Enterococcaceae. Vaginal casework
      samples showed results comparable to freshly collected ones; moreover the DNA
      extracted was successfully used for STR typing. Also mixtures of body fluids were
      analyzed, providing a microbiological signature compatible with the presence of
      microbes of oral, fecal and vaginal origin. The presented method can be useful in
      identifying biological fluids, and it is based on DNA technologies already
      available in forensic laboratories and feasible for further high throughput
      automation.

PMID- 22364793
TI  - Eminence-based medicine: the King is dead.

PMID- 22364792
TI  - Layer by layer self-assembly of poly[2-(methacryloyloxy) ethyl phosphorylcholine]
      multilayer via the ionic complexation with zirconium.
AB  - Zirconium-phosphonate (Zr-P) ionic complexation chemistry is explored as a new
      approach to fabricate poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC)
      multilayer film by layer-by-layer self-assembly method. Quartz crystal
      microbalance with dissipation (QCM-D) and optical ellipsometry measurements
      demonstrated that PMPC layer can be fully absorbed on each Zr(4+) layer. The
      thickness of the multilayer film with a good linear relationship was followed by
      the ellipsometry in situ adlayer characterization. The influence of pH of the
      PMPC and Zr(4+) solutions on the multilayer deposition were investigated by
      optical ellipsometry. QCM-D results indicated that the multilayer film is stable
      in a PBS flowing chamber at a high flow rate of 5.2*10(-3)m/s. The ellipsometry
      data demonstrated that 67.2% of the film still remained on the silicon wafer
      after being strong shaken in PBS at 80 rpm for 12h. The adsorption of bovine
      serum albumin (BSA) and fetal bovine serum (FBS) on the PMPC surface was
      monitored by the QCM-D and spectroscopic ellipsometry, and the results showed the
      multilayer film have excellent protein resistance.

PMID- 22364794
TI  - Evidence-based medicine: a strategy to reduce clinical uncertainty, resulting in
      improved patient outcomes and population health and reduced cost through
      improvements in care.

PMID- 22364795
TI  - Finding and evaluating renal evidence: bridging the knowledge gap.
AB  - Nephrologists often search for clinical information to guide patient care,
      especially in the chronic kidney disease patient population where information
      needs are complex. Applying evidence-based principles while searching for current
      high-quality information can be challenging. This article details the "6S"
      framework to approaching evidence-based information resources popularized by
      Haynes and colleagues. This hierarchal structure of resources includes "systems,"
      "summaries," "synopses of syntheses," "syntheses," "synopses of studies," and
      finally, "studies" with the intent of providing nephrologists with an efficient
      method of retrieving accurate, high-quality information. Accurate clinical
      decision support systems are ideal but are yet to reach their full potential.
      Summaries of best evidence for individual clinical problems are useful (UpToDate,
      DynaMed, Best Practice, and PIER). Syntheses of articles are an efficient way to
      understand the available evidence for a clinical question. The Cochrane Renal
      Review Group is a helpful resource which provides many systematic reviews in
      renal research. When using bibliographic databases, such PubMed, nephrologists
      can improve the precision of their search results with information filters. The
      application of accurate and current clinical knowledge is increasingly important
      in renal patient care. Better ways of achieving this will have large benefits.

PMID- 22364797
TI  - Confounding and control of confounding in nonexperimental studies of medications
      in patients with CKD.
AB  - Confounding is an important source of bias in nonexperimental studies, arising
      when the effect of an exposure on the occurrence of an outcome is distorted by
      the effect of some other factor. In nonexperimental studies of patients with CKD
      or who are on chronic dialysis, confounding is a significant concern owing to the
      high burden of comorbid disease, extent of required clinical management, and high
      frequency of adverse clinical events in this patient population. Confounding can
      be addressed in both the design stage (restriction, accurate measurement of
      confounders) and analysis stage (stratification, multivariable adjustment,
      propensity scores, marginal structural models, instrumental variable) of a study.
      Time-dependent confounding and confounding by indication are 2 special cases of
      confounding that can arise in studies of treatment effects and may require more
      sophisticated analytic techniques to adequately address. The availability and
      expanded use of large health care databases have ensured greater precision and
      have now placed the focus on validity. Addressing the major threats to validity,
      such as confounding, should be a first-order concern.

PMID- 22364796
TI  - Observational studies versus randomized controlled trials: avenues to causal
      inference in nephrology.
AB  - A common frustration for practicing Nephrologists is the adage that the lack of
      randomized controlled trials (RCTs) does not allow us to establish causality, but
      merely associations. The field of nephrology, like many other disciplines, has
      been suffering from a lack of RCTs. The view that without RCTs, there is no
      reliable evidence has hampered our ability to ascertain the best course of action
      for our patients. However, many clinically important questions in medicine and
      public health, such as the association of smoking and lung cancer, are not
      amenable to RCTs owing to ethical or other considerations. Whereas RCTs
      unquestionably hold many advantages over observational studies, it should be
      recognized that they also have many flaws that render them fallible under certain
      circumstances. We provide a description of the various pros and cons of RCTs and
      of observational studies using examples from the nephrology literature, and argue
      that it is simplistic to rank them solely based on preconceived notions about the
      superiority of one over the other. We also discuss methods whereby observational
      studies can become acceptable tools for causal inferences. Such approaches are
      especially important in a field like nephrology where there are myriads of
      potential interventions based on complex pathophysiologic states, but where
      properly designed and conducted RCTs for all of these will probably never
      materialize.

PMID- 22364798
TI  - Evidence-based practice in nephrology: critical appraisal of nephrology clinical
      research: were the correct statistical tests used?
AB  - Nephrologists rely on valid clinical studies to inform their health care
      decisions. Knowledge of simple statistical principles equips the prudent
      nephrologist with the skills that allow him or her to critically evaluate
      clinical studies and to determine the validity of the results. Important in this
      process is knowing when certain statistical tests are used appropriately and if
      their application in interpreting research data will most likely lead to the most
      robust or valid conclusions. The research team bears the responsibility for
      determining the statistical analysis during the design phase of the study and
      subsequently for carrying out the appropriate analysis. This will ensure that
      bias is minimized and "valid" results are reported. We have summarized the
      important caveats and components in correctly choosing a statistical test with a
      series of tables. With this format, we wish to provide a tool for the
      nephrologist/researcher that he or she can use when required to decide if an
      appropriate statistical analysis plan was implemented for any particular study.
      We have included in these tables the types of statistical tests that might be
      used best for analysis of different types of comparisons on small and on larger
      patient samples.

PMID- 22364799
TI  - Evidence-based practice in nephrology: systematic reviews.
AB  - A systematic review, the careful search and comprehensive analysis of all
      available data on a particular clinical question, is a useful tool for the busy
      clinician seeking to practice evidence-based medicine. When performed
      appropriately, they can provide a concise overview of the available literature.
      Meta-analysis is a method of mathematically combining the results of multiple
      individual studies, and it must be done in the setting of conceptual and
      statistical homogeneity. However, as with all forms of research, one must become
      familiar with the strengths and drawbacks of this type of evidence to critically
      appraise its validity.

PMID- 22364801
TI  - Evidence-based medicine and public policy: implications of nephrology.
AB  - The fundamentals of evidence-based medicine inform public policy and, in
      particular, the products derivative therefrom, namely, clinical practice
      guidelines, clinical performance measures, and point-of-care clinical decision
      making. Each provides a component of the foundation of a national quality
      enterprise. The national organizations engaged in developing and endorsing these
      applications and the interrelationships among these applications are outlined.
      The challenges being faced by these organizations and the implications of these
      initiatives for nephrology, in general, are discussed.

PMID- 22364800
TI  - Randomized controlled trials in nephrology: state of the evidence and critiquing
      the evidence.
AB  - The randomized controlled trial (RCT) remains the "gold standard" for the
      evaluation of therapies. Despite some progress during the past decade, the number
      and quality of published RCTs addressing the core issues for patients with CKD
      and with renal diseases, in general, lag behind other areas in internal medicine.
      The paucity of robust evidence results in fewer patients receiving evidence-based
      therapies in nephrology and fewer rigorous systematic reviews to inform
      nephrology practice and health care policy. Because trials of lower methodologic
      rigor continue to be published, the evidence-based practitioner must evaluate new
      evidence from the medical literature carefully before incorporating that evidence
      into their clinical practice. The types of errors that may limit the validity or
      applicability of evidence from RCTs is outlined. A detailed discussion of the
      most important design elements for the conduct of a high-quality RCT is described
      in the text. These considerations are placed into the context of critical
      appraisal tools. These tools allow the clinician to efficiently assess the
      quality of published RCTs and to determine how the new RCT evidence should change
      current best practice.

PMID- 22364802
TI  - [Treatment for intracranial aneurysms].
AB  - Aneurysm rupture is suspected in case of sudden, intense headache, sometimes
      associated with nausea or vomiting, focal neurologic deficit or loss of
      consciousness. Aneurysm rupture is a diagnostic and therapeutic emergency that
      has to be managed in highly specialized centers. Ruptured aneurysms have to be
      treated in emergency to avoid rebleeding. Endovascular approach is the first line
      treatment. The indications for treatment of unruptured have to be discussed
      according to several factors including patient's age, aneurysm size and location.
      Follow-up examinations are needed after aneurysm treatment (CTA, MRA, DSA).
      According to aneurysm risk factors, patients with aneurysms have to stop smoking
      and their blood pressure should be controlled on a regular basis and treated if
      needed.

PMID- 22364803
TI  - [Favorable evolution of a cutaneous vasculitis after pheochromocytoma excision].

PMID- 22364804
TI  - [A mange-like case...].

PMID- 22364805
TI  - [Indications for thrombolysis in ischemic stroke].
AB  - Cerebral MRI with angio-MR are more effective than CT scan for selecting patients
      with ischemic stroke for thrombolysis. The use of cerebral MRI has to be
      available 24h a day and everyday as a standardized emergency procedure. Off-label
      criteria for thrombolysis after acute ischemic stroke are too restritive and have
      to be revised. In acute ischemic stroke, imaging that shows the collateral
      circulation within the hypoperfusion area has to be used to estimate the
      potential of therapeutic revascularization. When there are contraindications for
      intravenous thrombolysis, the endovascular approach must be argued individually
      by neurologists and neurointerventionalists together.

PMID- 22364806
TI  - [Adult-onset Still disease in pregnancy].

PMID- 22364807
TI  - A smashing time at the tennis.

PMID- 22364808
TI  - Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism
      among Palestinians at Gaza Strip.
AB  - BACKGROUND: The G6PD c.563 C>T deficient mutation is endemic among Mediterranean
      populations but its clinical significance is not well delineated. We set up to
      estimate the proportion of G6PD deficient children presenting with hemolytic
      anemia at Al Nasser Pediatric Hospital at Gaza Strip, Palestine. We then
      established the prevalence of c.563T Mediterranean mutation and its linkage to
      c.1311 C>T polymorphism in this population. DESIGN AND METHODS: G6PD deficiency
      was identified in children presenting with hemolytic anemia at Al Nasser
      Pediatric Hospital by spectrophotometric measurement of G6PD activity. G6PD exon
      6 and exon 11 were amplified from genomic DNA and evaluated for c.563T mutation
      by sequencing and the c.1311T polymorphism by restriction fragment analysis.
      Seventy X-chromosomes (60 males and 5 females) from G6PD deficient patients and
      40 X-chromosomes from a control group known to be not G6PD deficient were tested.
      RESULTS: Over 80% of these children presenting with hemolytic anemia were G6PD
      deficient and 34% of these had the Mediterranean G6PD deficient variant. The
      allelic frequencies of Mediterranean c.563T and c.1311T polymorphisms among G6PD
      deficient patients were 0.33 and 0.38 respectively. The c.1311T polymorphism was
      linked in 95.2% of patients with the Mediterranean mutation, an allele frequency
      of 0.87, compared to the control non-G6PD deficient group with an allele
      frequency of 0.18. CONCLUSIONS: We conclude that G6PD deficiency accounts for
      majority of hemolytic anemia encountered in Gaza children treated at Al Nasser
      Pediatric Hospital Emergency department. The Mediterranean mutation c.563T, while
      not accounting for a majority of G6PD deficiency, is common among G6PD deficient
      Gaza Strip Palestinians and is frequently, but not always, linked to the c.1311T
      polymorphism. This work provides a foundation for the population screening of
      Palestinians for G6PD deficiency and for investigations of ancestral origin of
      the Mediterranean variant in world populations.

PMID- 22364809
TI  - Genetic portrait of Brazilian immigrant population living in Lisboa.

PMID- 22364810
TI  - Harnessing gammadelta T cells in anticancer immunotherapy.
AB  - gammadelta T lymphocytes are involved in the stress response to injured epithelia
      and in tissue homeostasis by limiting the dissemination of malignant or infected
      cells and by regulating the nature of the subsequent adaptive immune response.
      gammadelta T cells have potent MHC-unrestricted cytotoxicity, a high potential
      for cytokine release and broad-spectrum recognition of cancer cells, and as such,
      are attractive effectors for cancer immunotherapy. Current expectations are going
      beyond ex vivo manipulation of the Vgamma9Vdelta2 T subset, and target novel
      gammadelta T cell subsets, properties or receptors, to harness these
      unconventional T lymphocytes against cancer. This Opinion article discusses novel
      aspects of gammadelta T cell function during the course of anticancer therapies,
      as well as new avenues for their clinical implementation.

PMID- 22364811
TI  - Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid
      leukemia.
AB  - Ensuring adherence to therapy is a challenge in chronic diseases, particularly in
      cancers such as chronic myeloid leukemia (CML), where there has been increased
      availability and use of oral formulations. A conceptual model of adherence was
      developed based on findings from a comprehensive literature review, to inform
      strategies for improving adherence to oral CML therapies. A complex interplay of
      factors (including clinical, psychological and behavioural) influence adherence
      to such therapies. Healthcare professionals have a key role in promoting and
      facilitating adherence and future strategies should place greater emphasis on
      understanding patient-level experiences in order to create personalized
      solutions.

PMID- 22364812
TI  - Substituent effects on P2-cyclopentyltetrahydrofuranyl urethanes: design,
      synthesis, and X-ray studies of potent HIV-1 protease inhibitors.
AB  - The design, synthesis, and biological evaluation of novel C3-substituted
      cyclopentyltetrahydrofuranyl (Cp-THF)-derived HIV-1 protease inhibitors are
      described. Various C3-functional groups on the Cp-THF ligand were investigated in
      order to maximize the ligand-binding site interactions in the flap region of the
      protease. Inhibitors 3c and 3d have displayed the most potent enzyme inhibitory
      and antiviral activity. Both inhibitors have maintained impressive activity
      against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray
      crystal structure of 3c-bound HIV-1 protease revealed a number of important
      molecular insights into the ligand-binding site interactions.

PMID- 22364813
TI  - Radiosynthesis of [11C]BBAC and [11C]BBPC as potential PET tracers for orexin2
      receptors.
AB  - Radiosynthesis of [N-methyl-(11)C](S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H
      benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide ([(11)C]BBAC or
      [(11)C]3) and [N-methyl-(11)C] (S)-N-([1,1'-biphenyl]-2-yl)-1-(3-(1-methyl-1H
      benzo[d]imidazol-2-yl)propanoyl)pyrrolidine-2-carboxamide ([(11)C]BBPC or [(11)C]
      4), two potential PET tracers for orexin2 receptors are described. Syntheses of
      non-radioactive standards 3, 4 and corresponding desmethyl precursors 1, 2 were
      achieved from common intermediate (S)-2-([1,1'-biphenyl]-2-yl)-1-(pyrrolidin-2
      yl)ethanone. Methylation using [(11)C]CH(3)OTf in the presence of base in acetone
      afforded [(11)C]3 and [(11)C]4 in 30+/-5% yield (EOS) with >99 % radiochemical
      purities with a specific activity ranged from 2.5+/-0.5 Ci/MUmol (EOB). The logP
      of [(11)C]3 and [(11)C]4 were determined as 3.4 and 2.8, respectively. The total
      synthesis time was 30 min from EOB. However, PET scans performed in a rhesus
      monkey did not show tracer retention or appropriate brain uptake. Hence [(11)C]3
      and [(11)C]4 cannot be used as PET tracers for imaging orexin2 receptors.

PMID- 22364814
TI  - Synthesis of [12]aneN3-dipeptide conjugates as metal-free DNA nucleases.
AB  - In this Letter, a series of macrocyclic polyamine [12]aneN(3)-dipeptide
      conjugates as a new type of metal-free nucleases were synthesized and fully
      characterized with (1)H NMR, (13)C NMR, IR, and HR-MS. Results indicate that
      these conjugates can bind to calf thymus DNA mainly through electrostatic
      interaction and can cleave the plasmid DNA at 200 MUM (pH 7.2, 37 degrees C),
      with an acceleration of 10(6)-fold via hydrolytic pathway.

PMID- 22364815
TI  - Isolation and identification of antibacterial neo-compounds from the red ants of
      ChangBai Mountain, Tetramorium sp.
AB  - Three novel coumarin compounds along with two known amide alkaloids were isolated
      from a methanol extract of the red ants of ChangBai Mountain, Tetramorium sp.
      Their structures were identified on the basis of IR, 2D NMR ((1)H-(1)H COSY,
      HSQC, HMBC and NOESY) and HRESIMS analysis. Antibacterial activity of all the
      compounds was evaluated using KB paper diffusion through measurement of
      inhibiting zone. It was found that four of all the compounds exhibited
      significant inhibitory activity against Gram-positive bacteria Bacillus subtilis
      with MIC values of 25 MUg/ml (compounds 1-3) and 15 MUg/ml (compound 4).

PMID- 22364816
TI  - Contraindications to progestin-only oral contraceptive pills among reproductive
      aged women.
AB  - BACKGROUND: Progestin-only oral contraceptive pills (POPs) have fewer
      contraindications to use compared to combined pills. However, the overall
      prevalence of contraindications to POPs among reproductive-aged women has not
      been assessed. STUDY DESIGN: We collected information on contraindications to
      POPs in two studies: (1) the Self-Screening Study, a sample of 1267 reproductive
      aged women in the general population in El Paso, TX, and (2) the Prospective
      Study of OC Users, a sample of current oral contraceptive (OC) users who obtained
      their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican
      pharmacies (n=514). In the Self-Screening Study, we also compared women's self
      assessment of contraindications using a checklist to a clinician's evaluation.
      RESULTS: Only 1.6% of women in the Self-Screening Study were identified as having
      at least one contraindication to POPs. The sensitivity of the checklist for
      identifying women with at least one contraindication was 75.0% [95% confidence
      interval (CI): 50.6%-90.4%], and the specificity was 99.4% (95% CI: 98.8%-99.7%).
      In total, 0.6% of women in the Prospective Study of OC Users reported having any
      contraindication to POPs. There were no significant differences between clinic
      and OTC users. CONCLUSION: The prevalence of contraindications to POPs was very
      low in these samples. POPs may be the best choice for the first OTC oral
      contraceptive in the United States.

PMID- 22364817
TI  - Vaginal misoprostol aids in difficult intrauterine contraceptive removal: a
      report of three cases.
AB  - BACKGROUND: Intrauterine devices are the most used long-acting reversible
      contraceptive method worldwide. Under normal circumstances, removal of an
      intrauterine contraceptive (IUC) is an uncomplicated procedure requiring gentle
      traction on the string. STUDY DESIGN: We report three cases of nonvisible IUC
      strings where, following use of vaginal misoprostol, the IUC strings were
      visualized and the IUCs were removed intact with gentle traction. CONCLUSIONS:
      The uterotonic and uterocontractile effects following vaginal misoprostol
      facilitated removal in three cases of nonvisible IUC strings. We suggest that
      clinicians consider including vaginal misoprostol alone or prior to planned
      repeat office or procedure-clinic interventions for nonvisible IUC strings.

PMID- 22364818
TI  - Effect of two kinds of different combined oral contraceptives use on bone mineral
      density in adolescent women.
AB  - BACKGROUND: Steroid hormonal contraceptives are highly effective and widely used.
      Most studies have shown a negative effect of combined oral contraceptives (COCs)
      on the bone mineral density (BMD) of adolescents. The study was conducted to
      compare BMD among users of ethinylestradiol/desogestrel, users of
      ethinylestradiol/cyproterone acetate and nonhormonal control subjects in women
      aged 16-18 years. STUDY DESIGN: The study included 450 women 16-18 years of age.
      One hundred fifty women were using ethinylestradiol/desogestrel, 150 women were
      using ethinylestradiol/cyproterone acetate, and 150 women were using nonhormonal
      contraception as control subjects. BMD ofthe lumbar spine and femoral neck was
      obtained using dual-energy X-ray absorptiometry, and mean BMD changes in COCs
      users and nonusers were compared. RESULTS: At 24 months of treatment, lumbar
      spine and femoral neck mean BMD values in women (n=127) who used
      ethinylestradiol/desogestrel were slightly lower compared with baseline, but
      these effects did not reach statistical significance (p=.837 and p=.630,
      respectively). The mean lumbar spine and femoral neck BMD values in women (n=134)
      who used ethinylestradiol/cyproterone acetate were slightly higher compared with
      baseline, but there was no statistical significance (p=.789 and p=.756,
      respectively). The increases in mean percent change in lumbar spine and femoral
      neck BMD in the ethinylestradiol/cyproterone acetate group were less than those
      in the control group (1.88% vs. 0.30% and 0.98% vs. 0.49%, respectively). There
      were no significant differences in mean BMD of the lumbar spine and femoral neck
      between the users of ethinylestradiol/desogestrel or ethinylestradiol/cyproterone
      acetate and nonusers (p>.05). CONCLUSION: Our study indicates that 2 years of
      COCs therapy had no significant effect on bone density in adolescents, but it
      remains unknown whether therapy longer than 2 years has a significant adverse
      effect on the attainment of peak bone mass.

PMID- 22364819
TI  - Challenges in reconciling best interest and parental exercise of autonomy in
      pediatric life-or-death situations.
AB  - OBJECTIVE: To study attitudes regarding life-saving interventions. STUDY DESIGN:
      An Internet questionnaire describing 6 patients of different ages needing
      resuscitation was sent to members of the Norwegian Pediatric Association (n =
      676): a 24-week gestational age infant, a term infant, a 2-month-old infant, a 7
      year, a 50-year, and an 80-year-old individual. Neonates had similar or better
      described outcomes than older patients. RESULTS: A total of 266 people responded
      (39.4%). The majority would resuscitate all the patients except the 80-year-old.
      The majority thought that resuscitation was in the best interest of the younger 5
      patients, but fewer thought so for neonates (P < .05). Although the majority of
      the respondents thought that resuscitation was in the neonates' best interest
      (71% for 24-week-old and 75% for term infant), significantly more would accept
      comfort care at parental demand (62% for 24-week-old and 72% for term infant),
      unlike for other scenarios. Quality of life was used to justify decision making;
      25% used the length of the life for neonates to motivate their answers. Patients
      were prioritized for resuscitation in the following order: 2-month-old infant, 7
      year-old child with multiple disabilities, 50-year-old adult, the neonates, and
      lastly the 80-year-old individual. CONCLUSION: There are challenges in
      reconciling best interest and parental exercise of autonomy in pediatric life-or
      death situations. Neonates seem to be devalued.

PMID- 22364820
TI  - Heritability of respiratory infection with Pseudomonas aeruginosa in cystic
      fibrosis.
AB  - OBJECTIVE: To quantify the relative contribution of factors other than cystic
      fibrosis transmembrane conductance regulator genotype and environment on the
      acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis.
      STUDY DESIGN: Lung infection with Pa and mucoid Pa was assessed using a co-twin
      study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two
      definitions were used to establish infection: first positive culture and
      persistent positive culture. Genetic contribution to infection (ie, heritability)
      was estimated based on concordance analysis, logistic regression, and age at
      onset of infection through comparison of intraclass correlation coefficients.
      RESULTS: Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30
      pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76.
      Logistic regression adjusted for age corroborated genetic control of persistent
      Pa infection. The correlation for age at persistent Pa infection was higher in MZ
      twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, -0.352 to
      0.607), generating a heritability of 0.85. CONCLUSION: Genetic modifiers play a
      significant role in the establishment and timing of persistent Pa infection in
      individuals with cystic fibrosis.

PMID- 22364821
TI  - Hemifacial flushing after bathing and crying.

PMID- 22364822
TI  - Relationship between sleep position and risk of extreme cardiorespiratory events.
AB  - OBJECTIVE: To determine whether infants at sleep in the prone side positions are
      at higher risk for an extreme cardiorespiratory event compared with infants at
      sleep in the supine position. STUDY DESIGN: We used a case-control study to
      compare sleep position, determined with an accelerometer, in 116 infants during
      an extreme cardiorespiratory event with that in 231 matched control subjects (2
      per case) who did not experience any extreme events during monitoring. RESULTS:
      From calculation of adjusted ORs and 95% CIs, infants placed in the prone or side
      position were no more likely to experience an extreme cardiorespiratory event
      compared with infants at sleep in the supine position. We used conditional
      logistic regression to account for the matched design of the study and to adjust
      for potential confounders or effect-modifiers. CONCLUSION: These findings,
      coupled with our earlier observation that the peak incidence of severe
      cardiorespiratory events occurred before the peak incidence of sudden infant
      death syndrome, strongly suggest that the supine sleeping position decreases the
      risk of sudden infant death syndrome by mechanisms other than by decreasing
      extreme cardiorespiratory events detected by monitoring.

PMID- 22364823
TI  - Comparative prophylactic and therapeutic effects of intravenous labetalol 0.4
      mg/kg and nicardipine 20 MUg/kg on hypertensive responses to endotracheal
      intubation in patients undergoing elective surgeries with general anesthesia: a
      prospective, randomized, double-blind study.
AB  - BACKGROUND: Laryngoscopy and tracheal intubation (LTI) after induction of general
      anesthesia often cause hypertension and tachycardia. Labetalol and nicardipine
      have been used to prevent and treat acute cardiovascular responses to LTI.
      OBJECTIVE: The goal of this study was to compare the preventive and therapeutic
      effects of labetalol 0.4 mg/kg IV and nicardipine 20 MUg/kg IV on hypertensive
      responses to LTI during induction of general anesthesia. METHODS: Patients
      undergoing general anesthesia were randomly allocated to 4 groups. In part I
      (prevention), 80 patients were randomized to receive either 0.4 mg/kg of
      labetalol (n = 40) or 20 MUg/kg of nicardipine (n = 40) 4 minutes before LTI. In
      part II (treatment), patients were randomized to receive 0.4 mg/kg of labetalol
      (n = 40) or 20 MUg/kg of nicardipine (n = 40) after LTI if hypertension occurred.
      The number of additional study drug doses required by patients with hypertension
      (parts I and II) and time to return to normotension (part II) were recorded. Mean
      arterial pressure and heart rate were monitored, and rate-pressure product was
      calculated. Adverse events were also monitored. RESULTS: A total of 130 patients
      (72 patients in part I and 58 patients in part II) were included in the analysis.
      In parts I and II, the number of patients who required additional doses of the
      study drug because of persistent hypertension was lower in the nicardipine groups
      than in the labetalol groups (P < 0.05). Mean arterial pressure was lower and
      heart rate was significantly higher over time in the nicardipine groups compared
      with the labetalol groups (P < 0.05) in parts I and II. In part II, time to
      return to normotension was shorter in the nicardipine treatment group than in the
      labetalol treatment group (61 [21] vs 130 [46] seconds; P = 0.01). No statistical
      differences were observed in the incidence of adverse events except for
      tachycardia in part I (2 cases in the labetalol prevention group vs 18 cases in
      the nicardipine prevention group; P = 0.01). CONCLUSIONS: Patients who received
      nicardipine were less likely to require additional doses for either the
      prevention or treatment of hypertensive responses to LTI and responded to the
      study drug more rapidly than patients who received labetalol for the treatment of
      hypertensive responses to LTI. However, labetalol was associated with a lower
      incidence of tachycardia and less of an increase in rate-pressure product when
      used for the prevention of hypertension during LTI.

PMID- 22364824
TI  - Tolerability and dose proportional pharmacokinetics of pasireotide administered
      as a single dose or two divided doses in healthy male volunteers: a single
      center, open-label, ascending-dose study.
AB  - BACKGROUND: Pasireotide is a multireceptor-targeted somatostatin analogue with
      high binding affinity for somatostatin receptor subtypes SST 1, 2, 3, and 5.
      OBJECTIVE: To evaluate the safety profile, tolerability, and pharmacokinetic
      profile of pasireotide in single- and divided-dose regimens in healthy
      volunteers. METHODS: A single-center, open-label, ascending-dose study was
      performed in healthy volunteers. Pasireotide, 900, 1200, and 1500 MUg SC, was
      administered as either a single dose or as two divided doses given 12 hours
      apart, with a 7-day washout period between treatments. RESULTS: Seventeen men
      (median age, 26 years) were enrolled. Their median weight was 81 kg, and 65% were
      white. One participant dropped out because of a grade 2 adverse event; most other
      adverse events were mild and affected the gastrointestinal tract. Blood glucose
      concentration increased after pasireotide administration, but returned to normal
      within 10 hours. After single-dose administration, pasireotide plasma
      concentration peaked rapidly at 15 minutes to 1 hour after dosing, followed by a
      tri-exponential (alpha, beta, and gamma phases) decline over time. Mean t(1/2)
      values during the alpha, beta, and gamma phases were approximately 2 to 3, 12 to
      17, and 54 to 97 hours, respectively. In the single-dose cohort, the mean (SD)
      AUC(infinity) was 110 (29), 149 (42), and 188 (52) h . ng/mL in the 900-, 1200-,
      and 1500-MUg groups, respectively. Time to reach C(max) was 0.69 (0.41), 0.59
      (0.38), and 0.56 (0.18) hours in the 900-, 1200-, and 1500-MUg groups,
      respectively. AUC(infinity) values were similar in the single-dose and divided
      dose cohorts. Mean total body clearance was 8 to 9 L/h across the dosage groups
      and dosing regimens, indicating a linear pharmacokinetic profile between doses.
      CONCLUSIONS: When administered as a single- or divided-dose regimen, pasireotide
      had a favorable tolerability profile in this selected group of healthy male
      volunteers. Its pharmacokinetic profile indicated rapid absorption, low
      clearance, high volume of distribution, and a long terminal half-life.

PMID- 22364825
TI  - Proposal of an innovative benchmark for accuracy evaluation of dental crown
      manufacturing.
AB  - An innovative benchmark representing a dental arch with classic features
      corresponding to different kinds of prepared teeth is proposed. Dental anatomy
      and general rules for tooth preparation are taken into account. This benchmark
      includes tooth orientation and provides oblique surfaces similar to those of real
      prepared teeth. The benchmark is produced by additive manufacturing (AM) and
      subjected to digitization by a dental three-dimensional scanner. The evaluation
      procedure proves that the scan data can be used as reference model for crown
      restorations design. Therefore this benchmark is at the basis for comparative
      studies about different CAD/CAM and AM techniques for dental crowns.

PMID- 22364826
TI  - Four-year longitudinal performance of a population-based sample of healthy
      children on a neuropsychological battery: the NIH MRI study of normal brain
      development.
AB  - The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of
      Normal Brain Development is a landmark study in which structural and metabolic
      brain development and behavior are followed longitudinally from birth to young
      adulthood in a population-based sample of healthy children. Cross-sectional
      findings from the neuropsychological test battery have been previously described
      (Waber et al., 2007). The present report details 4-year longitudinal
      neuropsychological outcomes for those children who were aged 6 to 18 years at
      baseline (N = 383), of whom 219 (57.2%) completed all 3 visits. Primary
      observations were (1) individual children displayed considerable variation in
      scores across visits on the same measures; (2) income-related differences were
      more prominent in the longitudinal than in the cross-sectional data; (3) no
      association between cognitive and behavioral measures and body mass index; and
      (4) several measures showed practice effects, despite the 2-year interval between
      visits. These data offer an unparalleled opportunity to observe normative
      performance and change over time on a set of standard and commonly used
      neuropsychological measures in a population-based sample of healthy children.
      They thus provide important background for the use and interpretation of these
      instruments in both research settings and clinical practice.

PMID- 22364827
TI  - [Perilunate dislocations and fracture-dislocations of the wrist, a review of 17
      cases].
AB  - INTRODUCTION: The authors present the results of a retrospective series of 17
      cases of dislocations or perilunate fracture-dislocations of the carpus, treated
      in emergency (period of less than 7 days). The objective aim of our study was to
      evaluate the radioclinical fate prognosis of these lesions pathologies and their
      social commitment impact. PATIENTS AND METHODS: It is a retrospective study
      covering the period from July 2004 to December 2009 (or 54 months). Were included
      in the study, patients hospitalised for a pure dislocation or a perilunate
      fracture-dislocation authenticated confirmed by an x-ray postero-anterior and
      lateral views were included. The series included 15 men and two women, nine
      manual workers, with an average age of 38.9 years. Based on Herzberg radiological
      classification, the series included six pure perilunate dislocations (35%) and 11
      fracture-dislocations (59%) including seven forms trans-scapho-perilunate and
      four fractures of the lower end of radius. On the profile x-ray, 16 of the
      lesions were posterior displacement, including 12 stages I lesions (lunatum in
      place under the radius), and four stage II (lunatum dislocated in front of the
      radius). A patient had an anterior dislocation stage II, associated with a radial
      styloid fracture. All patients were operated using surgical treatment,
      percutaneous, either open pit, or open approaches combining with broaching
      scapholunate, scaphocapitate and triquetrolunate pinning. Then, an immobilization
      for 6 weeks was put in place and was performed using a forearm cast.
      Rehabilitation began as early as the removal of osteosynthesis was done at pin
      removal. RESULTS: The average decline follow-up in the series was 26 months. The
      mean score of Cooney was 63/100. There were two excellent results, two good
      results, seven middle moderate results, and six bad results. The average Quick
      DASH score was 24.6/55 and the PRWE 41/150. The average duration of the work
      stoppage leave was 8 months, including one retired. The average of flexion
      extension arc of the traumatized side was 77% (101 degrees ) in comparison to the
      healthy side. The average strength of the traumatized side was 71% (34kg) in
      comparison with the healthy side. The average radial-ulnar tilt arc of the
      traumatized side was 67% (37 degrees ) in comparison with the healthy side.
      DISCUSSION: There is no formal radioclinical prognostic in the radioclinic
      correlation. However, it seems to emerge that the timing and the type of support
      treatment bear the most important prognostic guarantors of a better result
      factors. Perilunate fracture-dislocations have major arthrogeneous arthrogenic
      potential, yet with a despite functional outcome consistent allowing resumption
      of recovery of past previous activities. It would seem that perilunate fracture
      dislocations have a better functional outcome than those of pure dislocations.
      Thus, this work is the beginning of a long-term study, including a larger number
      of patients.

PMID- 22364828
TI  - Identification of two phytotoxins, blumenol A and grasshopper ketone, in the
      allelopathic Japanese rice variety Awaakamai.
AB  - Aqueous methanol extracts of the traditional rice (Oryza sativa) variety
      Awaakamai, which is known to have the greatest allelopathic activity among
      Japanese traditional rice varieties, inhibited the growth of roots and shoots of
      cress (Lepidium sativum), lettuce (Lactuca sativa), timothy (Phleum pratense),
      Digitaria sanguinalis, Lolium multiflorum and Echinochloa crus-galli. Increasing
      the extract concentration increased the inhibition, suggesting that the extract
      of Awaakamai contains growth inhibitory substances. The extract of Awaakamai was
      purified and two main growth inhibitory substances were isolated and determined
      by spectral data as blumenol A and grasshopper ketone. Blumenol A and grasshopper
      ketone, respectively, inhibited the growth of cress shoots and roots at
      concentrations greater than 10 and 30 MUmol/L. The concentrations required for
      50% growth inhibition on cress roots and shoots were 84 and 27 MUmol/L,
      respectively, for blumenol A, and 185 and 76 MUmol/L, respectively, for
      grasshopper ketone. These results suggest that blumenol A and grasshopper ketone
      may contribute to the growth inhibitory effect of Awaakamai and may play an
      important role in the allelopathy of Awaakamai.

PMID- 22364829
TI  - Infected total hip arthroplasty revision: one- or two-stage procedure?
AB  - INTRODUCTION: Better outcomes have been reported for two-stage total hip
      arthroplasty (THA) revision for infection. However, one-stage revision
      arthroplasty remains an attractive alternative option since it requires only one
      operation. A decision tree has been developed by the authors in order to
      determine which type of surgical procedure can be performed safely. The goal of
      this study was to assess this decision tree for THA replacement in the case of a
      peri-prosthetic infection. HYPOTHESIS: A one-stage procedure may be as successful
      as a two-stage procedure provided some criteria are fulfilled. METHODS: A
      prospective study included 84 patients, all diagnosed with infected THA who had
      prosthesis replacement. A one-stage exchange was performed in 38 cases and a two
      stage procedure in 46 cases. A two-stage procedure was decided in the case of
      important bone loss or unidentified germ. Postoperatively, patients received
      intravenous antibiotics (six weeks), then oral antibiotics (six weeks). The main
      evaluation criterion was the rate of infection eradication at 2 years minimal
      follow-up since surgery. If new infection was suspected, a hip aspiration was
      performed to determine whether it was non-eradication (same germ) or a new re
      infection (other germ), which was not considered as a failure. RESULTS: The
      initial infection was cured in 83 out of 84 patients (98.8%), 38 (100%) for the
      one-stage group and 45 (97.8%) for the two-stage group. Three patients were re
      infected with different germs in the two-stage group. Eighty out of 84 (95.2%)
      patients were infection free, all patients (100%) of the one-stage group and 42
      patients (91.3%) of two-stage group. DISCUSSION: If some selection criteria were
      respected, a high success rate in THA replacement for infection may be achieved
      with a one-stage procedure. It permits to reduce the costs with no loss of chance
      for the patients. The decision tree was validated. LEVEL OF EVIDENCE: Level III;
      prospective case control study.

PMID- 22364830
TI  - Brassinosteroids induce plant tolerance against phenanthrene by enhancing
      degradation and detoxification in Solanum lycopersicum L.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are toxic to both plants and animals. The
      enhancement of plant tolerance and detoxification capacity is important for the
      plant-based remediation of PAHs. Therefore, we investigated the effects of 24
      epibrassinolide (EBR) on the metabolism of a three-ringed PAH (phenanthrene-PHE)
      and subsequent stress tolerance in tomato (Solanum lycopersicum L.) plants.
      Exposure to PHE (300 MUM) for 21 d significantly decreased biomass and net CO(2)
      assimilation (P(n)) but induced photoinhibition, malondialdehyde (MDA), H(2)O(2)
      and antioxidant enzymes. Obvious ultrastructural alterations were observed in the
      PHE-treated root tip cells. Importantly, the foliar application of EBR (0.1 MUM)
      significantly increased biomass, P(n) and antioxidant enzyme activities but
      decreased MDA and H(2)O(2) compared with PHE alone and saved the root cells from
      severe damage. The expression of detoxification genes (CYP90b3, GSH1, GST1),
      reduced glutathione (GSH) content and glutathione S-transferase activity in the
      EBR+PHE-treated plants were higher than those of PHE alone. Additionally, lower
      levels of PHE residues in the roots were observed as a result of EBR+PHE
      treatment. Taken together, our results strongly suggest an enhanced and
      coordinated detoxification and degradation of PHE by EBR.

PMID- 22364831
TI  - Arundo donax as a potential biomonitor of trace element contamination in water
      and sediment.
AB  - Environmental monitoring through living organisms is an effective technique of
      human impact assessment, based on reliable and cost-effective biological tools of
      control. In this study, roots, stems and leaves of the worldwide distributed
      macrophyte Arundo donax (giant reed) were tested as potential biomonitors of
      trace element contamination in water and sediment. In particular, the
      concentrations of the following elements were analyzed: Al, As, Cd, Cr, Cu, Hg,
      Mn, Ni, Pb, Zn. A two-year sampling was conducted in an urban watercourse of
      Catania (Sicily, Italy), affected by municipal and industrial discharges of
      wastewaters. Results showed that the amount of concentrations in plant tissues is
      significantly dependent on the kind of organ and element. Trace element
      concentrations decreased according to the pattern of root>leaf>stem, implying
      that roots acted as the main centers of bioaccumulation, and stems as transit
      organs as a consequence of the general high translocation from roots to leaves.
      Overall, A. donax showed a significant capacity of bioaccumulation in agreement
      with ecologically similar macrophytes. Positive correlations were found between
      trace concentrations in plant organs and sediment (Al, Cr, Mn, Ni, Zn), and water
      (Cu, Ni, Zn). The results of this study suggested that A. donax acts as an
      ecological indicator of environmental conditions, thus, its application may prove
      a useful tool during monitoring campaigns of wetlands.

PMID- 22364832
TI  - Hyperleukocytosis, leukostasis and leukapheresis: practice management.
AB  - Hyperleukocytosis, arbitrarily defined in acute leukemia as a white blood cell
      count greater than 100,000/mL, often is associated with increased morbidity and
      mortality in patients with leukemic processes. It can induce leukostasis, tumor
      lysis syndrome and disseminated intravascular coagulopathy and has significant
      prognostic implications with or without one of these clinical complications. The
      main sites that tend to be injured from the obstructions are the central nerve
      system and lungs. Despite characteristic clinical presentations, the diagnosis of
      leukostasis is rarely made with high confidence. The main goal of the management
      of hyperleukocytosis and/or leukostasis is to reduce the white blood cell count
      before starting induction chemotherapy. The cytoreduction can be achieved by
      either leukapheresis and/or hyroxyurea. The technical aspects, complications and
      efficacy of leukapheresis are discussed in the current article.

PMID- 22364833
TI  - Vorinostat, a histone deacetylase inhibitor, facilitates fear extinction and
      enhances expression of the hippocampal NR2B-containing NMDA receptor gene.
AB  - Histone acetylation, which alters the compact chromatin structure and changes the
      accessibility of DNA to regulatory proteins, is emerging as a fundamental
      mechanism for regulating gene expression. Histone deacetylase (HDAC) inhibitors
      increase histone acetylation and enhance fear extinction. In this study, we
      examined whether vorinostat, an HDAC inhibitor, facilitates fear extinction,
      using a contextual fear conditioning (FC) paradigm, in Sprague-Dawley rats. We
      found that vorinostat facilitated fear extinction. Next, the levels of global
      acetylated histone H3 and H4 were measured by Western blotting. We also assessed
      the effect of vorinostat on the hippocampal levels of NMDA receptor mRNA by real
      time quantitative PCR (RT-PCR) and protein by Western blotting. 2 h after
      vorinostat administration, the levels acetylated histones and NR2B mRNA, but not
      NR1 or NR2A mRNA, were elevated in the hippocampus. The NR2B protein level was
      elevated 4 h after vorinostat administration. Last, we investigated the levels of
      acetylated histones and phospho-CREB (p-CREB) binding at the promoter of the NR2B
      gene using the chromatin immunoprecipitation (ChIP) assay followed by RT-PCR. The
      ChIP assay revealed increases in the levels of acetylated histones and they were
      accompanied by enhanced binding of p-CREB to its binding site at the promoter of
      the NR2B gene 2 h after vorinostat administration. These findings suggest that
      vorinostat increases the expression of NR2B in the hippocampus by enhancing
      histone acetylation, and this process may be implicated in fear extinction.

PMID- 22364834
TI  - [Role of surgery in the management of pulmonary parasitosis].
AB  - Pulmonary parasitosis is scarcely encountered in France, and its diagnosis is
      quite difficult. If numerous parasites can be responsible for respiratory
      symptoms, only few of them can develop in the lung parenchyma and lead to
      complications necessitating a surgical treatment. The most common example is the
      hydatic disease of the lung. The authors review the biological cycles, clinical
      forms, diagnostic and treatment principles of those main lung parasites, which
      deserve surgical consideration.

PMID- 22364835
TI  - MicroRNAs in heart, lung and circulation (and beyond): life's ubiquitous code for
      regulating complex function.

PMID- 22364837
TI  - INTERIM guidelines for the diagnosis and management of familial
      hypercholesterolaemia.

PMID- 22364838
TI  - Decreased colonization of chicks by Salmonella enterica serovar Gallinarum
      expressing mannose-sensitive FimH adhesin from Salmonella enterica serovar
      Enteritidis.
AB  - To investigate the role of non-hemagglutinating type 1 fimbriae in the
      pathogenesis of Salmonella Gallinarum, the isogenic mutant elaborating type 1
      fimbriae with mannose-sensitive (MS) variant of the FimH adhesin from Salmonella
      Enteritidis and the mutant strain with no FimH expression were constructed. Their
      binding to chicken leukocytes in vitro and invasiveness in 1-day-old chicks were
      studied. Our results demonstrated that S. Gallinarum type 1 fimbriae with an
      endogenous variant of the FimH adhesin mediated mannose-resistant (MR) binding to
      avian leukocytes and did not bind to human epithelial cells. However, after
      allelic replacement of the FimH, mutated fimbriae with S. Enteritidis variant of
      the FimH adhesin bound to both cell types in a mannose-dependent manner. In chick
      model, S. Gallinarum expressing wild-type FimH variant colonized cecal tonsils
      and bursa of Fabricius more effectively and invaded the spleen and liver in
      greater numbers than S. Gallinarum fimH knockout strain or mutant expressing MS
      FimH variant from S. Enteritidis. The invasive potential of the latter was
      greatly reduced in chicks since no viable bacteria expressing MS variant of the
      adhesin could be recovered from intestinal lymphoid tissues or liver over a 6
      days course of infection. Together, these results demonstrate that the S.
      Gallinarum type 1 fimbriae with the endogenous MR variant of the FimH protein
      increase systemic dissemination of S. Gallinarum and colonization of internal
      organs in chicks indicating the importance of these adhesive structures in the
      virulence of S. Gallinarum.

PMID- 22364839
TI  - Objectification of cranial vault correction for craniosynostosis by three
      dimensional photography.
AB  - PURPOSE: Correction of craniosynostosis is necessary in predominant cases.
      Surgical planning usually requires a preoperative CT to estimate the bony and
      intracerebral structures. A postoperative CT scan would involve a significant
      dose of radiation, which carries an elevated risk of malignant tumor development
      in later life. This study was performed to demonstrate the quality of three
      dimensional (3D) photogrammetry when objectifying perioperative changes in
      craniofacial surgery. PATIENTS AND METHODS: Twenty-eight patients with different
      premature craniosynostoses were analyzed photogrammetrically before and after
      surgical correction. 3D changes in cranial distances, symmetry and volumes were
      evaluated. A statistical covariance analysis excluded changes in cranial shape
      caused by physiological head growth. RESULTS: The Cephalic Index in Scaphocephaly
      changed from 75.1% to a median value of 77.4%. The anterior symmetry ratio for
      coronal synostoses improved from 0.943 to 0.949 (a value of 1.0 represents
      perfect symmetry). The posterior symmetry ratio improved from 0.733 to 0.808
      postoperatively in one single lambdoidal synostosis. In trigonocephaly, the
      median anterior skull volume rose from 528 to 601 ml. CONCLUSIONS: 3D
      photogrammetry has great potential to track and objectify the clinical course of
      surgical correction of craniosynostoses. Craniofacial changes become highly
      reproducible and demonstrate clinical utility based on this technology.

PMID- 22364840
TI  - Reducing electromagnetic irradiation and fields alleviates experienced health
      hazards of VDU work.
AB  - Word Heath Organisation (WHO) outlined in 2005 recommendations, how to treat
      people suffering from the functional impairment electrohypersensitivity in its
      document "Electromagnetic fields and public health". Unfortunately the reduction
      of electromagnetic fields was not considered as a treatment option. The aim of
      the current study was to shield the computer user from the emitted
      electromagnetic irradiation and fields and to correlate that to the subjective
      symptoms reported by electrohypersensitive volunteers. The irradiation of the
      shielding cabinets was recorded. They housed either separate computer screens or
      whole laptops. When the volunteers had used the shielding cabinet for 1-7 years,
      they were able work with their computers whole working day, Those who had used
      the shielding cabined for 2-3 months were partially symptom free. The person who
      had used the cabinet only for 1 week reported some alleviation of her nausea. IN
      CONCLUSION: it seems that reducing the electromagnetic irradiation of the
      computer can lessen the symptoms of electrohypersensitivity and permit working
      without problems. Further studies are needed to clarify how the symptoms of
      different organ systems recover and make computer users to work also
      professionally.

PMID- 22364841
TI  - The unrecognized effects of the volume and composition of the resuscitation fluid
      used during the administration of blood products.
AB  - BACKGROUND: Recent publications have reported the severe adverse events
      associated with blood products but have not considered the effect of the volume
      and composition of the resuscitative fluids infused with the blood products.
      METHODS: Injury leads to cellular reaction characterized by insulin resistance
      during which glucose cannot enter muscle and fat cells. In all cells,
      mitochondrial pyruvate dehydrogenase activity is decreased during insulin
      deficiency leaving cells deficient in substrates needed to power the Krebs cycle
      and make ATP. RESULTS: d-beta-Hydroxybutyrate, a normal ketone body metabolite,
      enters cells on the monocarboxylate transport mimicking the action of insulin and
      bypassing the enzymatic block at PDH. Metabolism of ketone bodies increases
      efficiency of mitochondrial energy production and cellular ATP level. CONCLUSION:
      Infusion of 250 ml of 600 mM Na d-beta-hydroxybutyrate solution, with the same
      osmotic strength as the hypertonic NaCl solution currently being used, would
      correct insulin resistance, provide energy substrates for cells to produce ATP,
      correct the tendency of injured tissue to swell due to decreased energy of ionic
      gradients and correct acidosis observed in hemorrhage.

PMID- 22364842
TI  - From individuals to populations: impacts of environmental pollution on natural
      eelpout populations.
AB  - Investigating how individuals are affected by environmental pollution is
      relatively straightforward, for example through conducting field studies or
      laboratory toxicity tests. Exploring such effects at a population level is
      considerably more difficult. Nonetheless, the exploration of population-level
      effects is important as the outcomes may differ from those seen at the individual
      level. Eelpout (Zoarces viviparus L.) have been used for several years as a
      bioindicator for hazard substances in both the field and laboratory tests, and
      individual effects on reproduction have been reported. However, the influence of
      these effects at the population level remained unexplored. In this study, four
      Leslie matrix models were parameterized using data from non-polluted eelpout
      populations (Skagerrak, Baltic Proper, Gulf of Bothnia and Gulf of Finland). The
      four sites represent an environmental gradient in salinity. Furthermore, life
      history data revealed differences between the sites with growth rate, fecundity,
      age at maturity and longevity being the most significant. The effect of pollution
      on natural eelpout populations was then simulated by combining the outputs from
      the Leslie matrices with data from laboratory and field studies exploring
      reproductive impairment in contaminated environments. Our results show that
      despite differences in life-history characteristics between sites, survival of
      early life stages (i.e. larvae and zero-year-old fish) was the most important
      factor affecting population growth and persistence for all sites. The range of
      change in survival of larvae necessary to change population dynamics (i.e.
      growth) and persistence is well within the range documented in recipient and
      experimental studies of chemicals and industrial waste waters. Overall, larval
      malformation resulting from environmental pollution can have large effects on
      natural populations, leading to population losses and possibly even extinction.
      This study hereby contributes valuable knowledge by extending individual-level
      effects of environmental contaminants to the population level.

PMID- 22364843
TI  - Stable isotope ratios and mercury levels in red meat products from baleen whales
      sold in Japanese markets.
AB  - We analyzed the delta(13)C, delta(15)N and delta(18)O values and Hg concentration
      in red meat products originating from the predominant types sold in Japan for
      human consumption: two populations of common minke (J- and O-types), Bryde's and
      sei whales in the western North Pacific Ocean, and fin and Antarctic minke whales
      in the Southern Ocean. The order of the trophic positions, evaluated by
      delta(15)N values and Hg concentrations, coincided with their known feeding
      habits: common minke (J-type)=common minke (O-type)> Bryde's >= sei >= Antarctic
      minke >= fin. The Hg concentrations in the combined samples from the six samples
      were significantly correlated with their delta(15)N values (gamma=0.455, n=66,
      p<0.05), reflecting overall differences in the trophic level. This correlation
      was not significant for within-species comparison for the common minke (J- and O
      types) or the Bryde's whale, probably reflecting the higher delta(15)N value and
      lower Hg concentration in the North Pacific Ocean around Japan. Determination of
      delta(13)C, delta(15)N and delta(18)O could be used to discriminate between the
      red meat products originating from the whale species in the North Pacific and
      Southern Oceans. However, the four whale species or populations in the Pacific
      Ocean could not be discriminated on basis of these values, nor could the two
      species in the Southern Ocean. Positive correlations between the delta(13)C and
      delta(15)N values and negative correlations between the delta(15)N and delta(18)O
      values and the delta(13)C and delta(18)O values, probably reflecting migration
      patterns, were found in some whale species in the North Pacific and Southern
      Oceans.

PMID- 22364844
TI  - Subchronic exposure to atrazine induces biochemical and histopathological changes
      in the gills of a Neotropical freshwater fish, Prochilodus lineatus.
AB  - The impact of acute (48 h) and subchronic (14 days) exposures to environmentally
      realistic atrazine concentrations (2, 10 and 25 MUg L(-1)) were evaluated on the
      gills of Prochilodus lineatus by assessing the activity of superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase
      (GST), the levels of reduced glutathione (GSH) and lipid peroxide (LPO) as well
      as the histopathological damage. Acute and subchronic exposure to atrazine at 2
      or 25 MUg L(-1) did not change the activities of GST, SOD, CAT or GPx or the
      concentrations of GSH and LPO; however, subchronic exposure to 10 MUg L(-1)
      increased the activity of GST, SOD and CAT and the LPO level. Histopathological
      indexes indicated normal gill function with scattered epithelial changes after
      acute and chronic exposure to 2 or 10 MUg L(-1) of atrazine; however, fish
      chronically exposed to 25 MUg L(-1) of atrazine, although had scattered lesions,
      the severity of lesions resulted in slightly to moderately gill damage. Acute
      exposure to atrazine decreased the type 3 MCs (containing acid mucosubstances
      with sulfate esters) in fish exposed to 2 or 10 MUg L(-1) and increased the type
      4 MCs (containing all types of mucosubstances) in fish exposed to 25 MUg L(-1).
      Chronic exposure to atrazine reduced the type 3 MCs in fish exposed to 10 or 25
      MUg L(-1). The gills showed a low sensitivity to atrazine after acute exposure.
      However, the persistence of atrazine in water (subchronic exposure) promoted an
      increase of LPO levels in the gills and increased the frequency and severity of
      histopathological changes. The decreased density of type 3 MCs in fish exposed to
      atrazine suggests a mechanism to wash toxic substances away from the gill
      surface.

PMID- 22364845
TI  - The Maori foot exhibits differences in plantar loading and midfoot morphology to
      the Caucasian foot.
AB  - The question being addressed in the current study was whether the diabetic Maori
      foot was more or less prone to ulceration than the diabetic New Zealand Caucasian
      (NZC) foot. Harris mat and pedobarographic analyses were employed to assess
      static and dynamic foot morphology and plantar loading in 40 Maori and NZC
      diabetic and non-diabetic participants. Significantly higher peak pressures were
      exhibited by the diabetic Maori participants compared to their NZC peers at the
      central forefoot. Significantly higher static and dynamic arch index values and
      significantly higher sub-arch angle values were exhibited by the non-diabetic
      Maori participants compared to their NZC peers. The latter findings suggest that
      healthy Maori may have a predisposition towards having a flatter foot than
      healthy NZC, which may have footwear design implications.

PMID- 22364847
TI  - Integration of health and environment through health impact assessment: cases
      from three continents.
AB  - Despite the strong linkage between environment and health, institutions
      responsible for these fields operate in largely fragmented ways with limited
      interaction. As illustrated in the recent engagement between health and urban
      planning institutions, inter-institutional cooperation could support more
      effective and politically acceptable solutions for both local and global
      problems. Analysis of three case-studies, from three different continents, shows
      that HIA might serve to promote synergies among health and environmental
      disciplines in different local contexts, and could lead to institutional and
      procedural changes that promote health. Case examples provided supportive
      evidence for these effects, despite differences in approaches to HIA and
      governance levels. Obstacles to the use of HIA for inter-institutional
      integration also differed between countries. Lessons learned could support
      cooperation in other common interests of health and environment disciplines such
      as research, training and preparedness, and mitigation of public health
      emergencies related to the environment.

PMID- 22364846
TI  - Comparison of functional and morphologic characteristics of mice models of noise
      induced hearing loss.
AB  - OBJECTIVES: This study was conducted to compare morphologic and audiologic
      changes after noise exposure in two different strains of mice (CBA and C57) and
      to create morphologically proven models of noise-induced hearing loss. METHODS:
      Mice were exposed to white noise at 110-dB sound-pressure level for 60 minutes at
      the age of 1 month. Hearing thresholds and outer hair cell functions were
      evaluated by auditory brainstem response recordings and distortion product
      otoacoustic emission immediately and 22 days after noise exposure. Cochlear
      pathology was observed and compared by light and electron microscopic studies.
      RESULTS: Both mice strains showed hearing threshold shifts with decreased outer
      hair cell function immediately and 22 days after noise exposure. More severe
      auditory brainstem response threshold shifts were observed in C57 mice compared
      with CBA mice at click, 8-, 16-, and 32-kHz tone-burst stimuli. A cochlear
      morphologic study demonstrated predominant outer hair cell degeneration at all
      turns of the cochlea; degeneration was most severe at the basal turn in both mice
      strains. A scanning electron microscopic study revealed more severe
      ultrastructural damage of outer hair cells at each turn of the cochlea in C57
      mice. The lateral wall of the cochlea was more severely degenerated in CBA mice.
      CONCLUSION: Both mice strains showed consistent, permanent noise-induced hearing
      loss with different susceptibilities and site vulnerabilities. Further studies to
      investigate the mechanism of the different degree and cochlear site vulnerability
      to noise exposure between two mice strains are necessary.

PMID- 22364848
TI  - Juvenile-onset permanent weakness in muscle phosphofructokinase deficiency.
AB  - We describe a 41-year-old Moroccan woman with phosphofructokinase (PFK)
      deficiency who presented slowly progressive muscular weakness since childhood,
      without rhabdomyolysis episode or hemolytic anemia. Deltoid biopsy revealed
      massive glycogen storage in the majority of muscle fibers and polysaccharide
      deposits. PFK activity in muscle was totally absent. A novel homozygous non-sense
      mutation was detected in PFKM gene. Our observation suggests that juvenile-onset
      fixed muscle weakness may be a predominant clinical feature of PFK deficiency.
      Vacuolar myopathy with polyglucosan deposits remains an important morphological
      hallmark of this rare muscle glycogenosis.

PMID- 22364849
TI  - Collaborative evaluation within a framework of stakeholder-oriented evaluation
      approaches.
AB  - Collaborative Evaluation systematically invites and engages stakeholders in
      program evaluation planning and implementation. Unlike "distanced" evaluation
      approaches, which reject stakeholder participation as evaluation team members,
      Collaborative Evaluation assumes that active, on-going engagement between
      evaluators and program staff, result in stronger evaluation designs, enhanced
      data collection and analysis, and results that stakeholder understand and use.
      Among similar "participant-oriented" evaluation approaches (Fitzpatrick, Sanders,
      & Worthen, 2011), Collaborative Evaluation distinguishes itself in that it uses a
      sliding scale for levels of collaboration. This means that different program
      evaluations will experience different levels of collaborative activity. The
      sliding scale is applied as the evaluator considers each program's evaluation
      needs, readiness, and resources. While Collaborative Evaluation is a term widely
      used in evaluation, its meaning varies considerably. Often used interchangeably
      with participatory and/or empowerment evaluation, the terms can be used to mean
      different things, which can be confusing. The articles use a comparative
      Collaborative Evaluation Framework to highlight how from a theoretical
      perspective, Collaborative Evaluation distinguishes itself from the other
      participatory evaluation approaches.

PMID- 22364850
TI  - Vocal cord adduction causing obstructive sleep apnea from vagal nerve
      stimulation: case report.
AB  - A recognized complication of vagal nerve stimulation is new or worsening sleep
      apnea. Its pathophysiology is not clearly understood. We report a patient with
      obstructive sleep apnea that was directly associated with vagal nerve stimulation
      causing recurring vocal cord adduction. Adjusting the stimulator settings
      resolved the problem.

PMID- 22364851
TI  - Standardized childhood fitness percentiles derived from school-based testing.
AB  - OBJECTIVE: To develop a statewide school-based program of measuring and reporting
      cardiovascular fitness levels in children, and to create age- and sex-specific
      cardiovascular fitness percentile-based distribution curves. STUDY DESIGN: A
      pilot study validated cardiovascular fitness assessment with Progressive Aerobic
      Cardiovascular Endurance Run (PACER) testing as an accurate predictor of
      cardiovascular fitness measured by maximal oxygen consumption treadmill testing.
      Schools throughout the state were then recruited to perform PACER and body mass
      index (BMI) measurement and report de-identified data to a centralized database.
      RESULTS: Data on 20 631 individual students with a mean age 12.1 +/- 2.0 years,
      BMI of 21.4 +/- 5.1, and a cardiovascular fitness measured with PACER of 29.7 +/-
      18.2 laps (estimated maximal oxygen consumption of 36.5 mL/kg/min) were submitted
      for analysis. Standardized fitness percentiles were calculated for age and sex.
      CONCLUSIONS: This study demonstrates the feasibility of performing, reporting,
      and recording annual school-based assessments of cardiovascular fitness to
      develop standardized childhood fitness percentiles on the basis of age and sex.
      Such data can be useful in comparing populations and assessing initiatives that
      aim to improve childhood fitness. Because health consequences of obesity result
      from both adiposity and physical inactivity, supplementation of BMI measurement
      with tracking of cardiovascular fitness adds a valuable tool for large-scale
      health assessment.

PMID- 22364853
TI  - Comparative effectiveness research using the electronic medical record: an
      emerging area of investigation in pediatric primary care.

PMID- 22364854
TI  - Familial hypercholesterolemia: a decade of progress, part 2.

PMID- 22364855
TI  - Laparoscopic prosthetic hiatal reinforcement for large hiatal hernia repair.
AB  - BACKGROUND: Large hiatal hernia (LHH) is defined by a hiatal defect larger than
      6cm; repair is indicated whenever it becomes symptomatic. As the risk of
      recurrence after most techniques is relatively high, laparoscopic repair with
      prosthetic reinforcement of the hiatus has been proposed to reduce the recurrence
      rate. Our technique and outcomes are reported. PATIENTS AND METHODS: Laparoscopic
      prosthetic hiatal reinforcement was performed in 58 patients between August 1997
      and October 2009. Prolene((r)), Mersilene((r)), Goretex((r)), and Parietex((r))
      were the four types of prosthetic material used. Since January 2004, the double
      sided V shaped Crurasoft((r)) mesh was introduced. Surgical evaluation was based
      on anatomical and functional criteria: the anatomical results included the
      presence of recurrent hiatal hernia or esophageal stricture as evaluated by an
      upper gastrointestinal (UGI) series; functional evaluation was based on a
      questionnaire concerning long-term patient satisfaction according to the Visick
      score. Median follow-up was 51 months. RESULTS: Postoperative UGI series were
      performed during the initial hospitalization in 37 patients: results were judged
      to be satisfactory. A routine follow-up UGI series was obtained at 8 months and
      one year in 46 patients. Two patients underwent reoperation for lower esophageal
      stricture at 6 months and 16 months. Forty-five patients (77.6%) were
      reevaluated. Of these, 29 patients (64.4%) were free of symptoms with a good
      quality of life, eight patients (17.7%) complained of moderate dysphagia and two
      patients (4.4%) had severe dysphagia. Four patients (8.9%) had moderate pyrosis
      while severe pyrosis requiring long term PPI treatment was observed in three
      patients (6.7%). No prosthesis-induced ulceration or perforation was noted. Late
      follow-up UGI series, performed in 21 patients, showed two patients with severe
      stricture and a single case of recurrence, but neither of these patients required
      surgical management. CONCLUSION: The addition of mesh reinforcement to surgical
      repair of large hiatal defects is safe and beneficial in terms of quality of
      life.

PMID- 22364856
TI  - Ultrasound-guided intralesional photocoagulation of intramuscular vascular
      malformation in the masseter muscle.

PMID- 22364857
TI  - Platyhelminthes in tongue--a rare case and review.
AB  - Humans are the only known definitive host of the tapeworm Taenia solium and
      become a carrier by eating undercooked pork contaminated with "Cysticercus
      cellulosae" (cysticerci). Pigs act as an intermediate host and acquire
      cysticercosis by ingestion of eggs or proglottids from human feces, which develop
      into cysticerci within tissue, mostly without causing clinical symptoms in the
      host. Cysticercosis occurs in humans in a context of "fecal peril" by ingestion
      of egg-contaminated soil, water, vegetation, or auto-infestation. It has been
      reported in the published data that the separation of swine from humans, healthy
      cooking, and hygienic practices would lead to the eradication of the disease.
      However, cysticercosis is still a major public health problem in endemic regions,
      with more than 50 million infected people and is now a re-emerging disease in
      industrialized countries owing to human migration. It is the second most common
      cause of seizures in tropical countries. We report a case of oral cysticercosis
      in a 28-year-old woman who presented with a painless swelling in the ventral
      portion of the tongue. An excisional biopsy was performed, and histopathologic
      examination revealed a cystic cavity containing the tapeworm.

PMID- 22364858
TI  - Small bolus of esmolol effectively prevents sodium nitroprusside-induced reflex
      tachycardia without adversely affecting blood pressure.
AB  - PURPOSE: Hypotensive anesthesia with sodium nitroprusside (SNP) often is
      associated with reflex tachycardia. The purpose of this study was to investigate
      whether a small bolus of esmolol could counteract SNP-induced reflex tachycardia
      and sympathetic activation without affecting blood pressure. MATERIALS AND
      METHODS: Using a time-series study design, 27 healthy young patients scheduled
      for mandibular osteotomy were enrolled in this study. General anesthesia was
      maintained with 2% sevoflurane and 67% nitrous oxide in oxygen. SNP was
      administered to decrease the mean arterial pressure to 55 to 65 mm Hg. When heart
      rate (HR) increased reflexively to higher than 95 beats/min from SNP-induced
      hypotension, esmolol 0.5 mg/kg was given. Blood pressure and HR were measured,
      and the low-frequency component (0.04 to 0.15 Hz) of systolic blood pressure
      variability and high-frequency component (0.15 to 0.4 Hz) of HR variability were
      calculated to evaluate the autonomic condition. Data were analyzed using 1-way
      analysis of variance after multiple comparisons or t test. P < .05 was considered
      statistically significant. RESULTS: Of the 27 patients analyzed, 19 patients
      (70%) required esmolol. In these patients, SNP caused an increase in the low
      frequency component of systolic blood pressure variability and a decrease in the
      high-frequency component of HR variability, leading to tachycardia (HR range,
      95.9 +/- 7.3 to 106.7 +/- 7.4 beats/min; P < .001). Esmolol suppressed the
      effects of SNP on the low-frequency component of systolic blood pressure
      variability and high-frequency component of HR variability, resulting in an
      immediate decrease in HR to 86.9 +/- 6.2 beats/min (P < .001), whereas mean
      arterial pressure remained unchanged. CONCLUSIONS: A small bolus of esmolol can
      suppress reflex tachycardia without significantly changing mean arterial
      pressure. Thus, esmolol restores the autonomic imbalance induced by SNP during
      hypotensive anesthesia.

PMID- 22364859
TI  - What are orthognathic patients' expectations of treatment outcome--a qualitative
      study.
AB  - PURPOSE: Patient's expectations of treatment outcome are one of the key
      determinants of satisfaction. The aim of this study was to evaluate orthognathic
      patients' expectations of the outcome of orthognathic treatment. METHODS: This
      study was a cross-sectional qualitative study involving in-depth interviews with
      patients with dentofacial deformities. Patients who were about to commence
      orthognathic treatment were recruited from new-patient clinics. Inclusion
      criterion were patients of any ethnicity 16 years or older who were about to
      commence orthognathic treatment to correct a dentofacial deformity. Exclusion
      criteria were patients who had previously received orthognathic treatment, who
      were younger than 16 years, and those with congenital craniofacial anomalies or
      acquired defects. The data were analyzed using a framework approach to management
      and critical qualitative theory, which involved identifying the main themes and
      subthemes. RESULTS: Eighteen adult patients 18 to 40 years old were interviewed;
      9 were women and 9 were men. Most were Caucasian and 6 were from the black and
      minority ethnic group. Participants' expectations could be divided broadly into 2
      main categories: expectations of actual physical changes and expectations of the
      effects that these physical changes would indirectly have on them (nonphysical
      changes). In addition, a typology of patients, based on expectations, was
      identified, whereby patients could be classified as metamorphosizers,
      pragmatists, shedders, or evolvers, together with implications and suggestions
      for practice. CONCLUSIONS: These findings represent a new insight into the
      complex issues of managing patient expectations and satisfaction. The clinical
      relevance of identifying expectations is not just to ration treatment or identify
      those who will make good or bad candidates for treatment, but to be able to offer
      them additional support to enhance satisfaction with the outcome. This highlights
      the need for a qualitative methodology to complete the full circle of evidence
      based practice.

PMID- 22364860
TI  - The role of maxillary osteotomy in the treatment of arhinia.
AB  - PURPOSE: Arhinia is a very rare malformation, and only 41 cases are described in
      the literature. Given its rarity, there is no standardized surgical protocol.
      This article describes our preferred treatment, which underlines the importance
      of maxillary osteotomy for obtaining satisfactory results. METHODS: We observed 3
      girls with arhinia, 2 of whom were treated by a 2-step surgical protocol. During
      the first phase, the patients underwent maxillary osteotomy with the creation of
      a new epithelium-lined nasal cavity. A skin expander was also placed in the
      forehead. During the second step, an external nose was created in both patients
      from the expanded forehead flap with local perinasal flaps and costochondral
      grafts. RESULTS: Both reconstructions were viable and esthetically acceptable. No
      internal nose restenosis was observed. CONCLUSIONS: On the basis of our
      experience, maxillary osteotomy should be considered part of an integrated
      approach in treating arhinia.

PMID- 22364861
TI  - ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal
      differentiation.
AB  - Disrupted epidermal differentiation characterizes numerous diseases that impact
      >25% of the population. In a search for dominant mediators of differentiation, we
      defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750
      controlled genes mutated in numerous human skin diseases, including FLG, LOR,
      LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an
      evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator,
      p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750
      restored differentiation to p63-deficient tissue, suggesting that it acts
      downstream of p63. A search for functionally important ZNF750 targets via
      analysis of ZNF750-regulated genes identified KLF4, a transcription factor that
      activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites
      flanking the transcriptional start site and controls its expression. ZNF750 thus
      directly links a tissue-specifying factor, p63, to an effector of terminal
      differentiation, KLF4, and represents a potential future target for disorders of
      this process.

PMID- 22364863
TI  - Three-year visual acuity outcomes after Descemet's stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To evaluate the long-term improvement of visual acuity after Descemet's
      stripping automated endothelial keratoplasty (DSAEK) surgery. DESIGN:
      Retrospective analysis of a noncomparative, interventional case series.
      PARTICIPANTS: One hundred eight patients undergoing DSAEK surgery for Fuchs'
      endothelial dystrophy and pseudophakic bullous keratopathy without other ocular
      comorbidities who completed a full 3-year follow-up period. METHODS:
      Postoperative best spectacle-corrected visual acuity (BSCVA) was recorded at 6,
      12, 24, and 36 months. Improvement in BSCVA between each time point was evaluated
      using paired-samples t tests. Subanalysis evaluating the percentage of eyes
      achieving a BSCVA of 20/20, 20/25, 20/30, and 20/40 at each time point was
      performed. MAIN OUTCOME MEASURES: Improvement in postoperative BSCVA. RESULTS:
      There was a statistically significant trend toward improvement in average BSCVA
      with time at postoperative month 6 and postoperative years 2 and 3. There were
      also increasing proportions of eyes reaching vision of 20/20, 20/25, and 20/30
      from 6 months to 1 year, 1 year to 2 years, and 2 years to 3 years. The
      percentage of patients achieving 20/25 BSCVA improved from 36.1% at 6 months to
      70.4% at 3 years after surgery. A similar increase in the percentage of patients
      reaching a BSCVA of 20/20 after DSAEK surgery also was observed from 11.1% at 6
      months to approximately 47.2% at 3 years. CONCLUSIONS: There is gradual
      improvement of visual acuity over time after DSAEK surgery for Fuchs' endothelial
      dystrophy and pseudophakic bullous keratopathy in patients without other vision
      limiting ocular comorbidities. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 22364864
TI  - Longitudinal measures of visual function, tumor volume, and prediction of visual
      outcomes after treatment of optic pathway gliomas.
AB  - PURPOSE: To examine longitudinal changes in visual acuity, tumor volume, and
      visual evoked potentials (VEP) before and after treatment in children with optic
      pathway gliomas. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one
      patients (0.7-9 years of age). METHODS: Patients initially were treated either by
      chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with
      serial magnetic resonance imaging, age-corrected visual acuity measurements in
      logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP.
      Longitudinal visual outcome data were obtained on average for 9 years (range, 4
      16 years). Tumor volumes before and after treatment were estimated in 15
      patients. Multivariate regression was used to predict visual outcomes. MAIN
      OUTCOME MEASURES: Visual acuity, relative tumor volumes, and VEP. RESULTS: Before
      treatment, 81% of patients had reduced visual acuity and 81% had optic nerve
      pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment,
      tumor volume decreased in 53%, stabilized in 27%, and progressively increased in
      20%. Treatment arrested the rapid decline in visual acuity loss and stabilized
      visual acuity for 4 to 5 years. The rate of visual acuity decline was not
      correlated with tumor shrinkage. Sixty-two percent of patients required
      additional treatment with either chemotherapy or radiation because of tumor
      growth or progressive loss of visual function. Visual acuity at last examination
      was stable or improved in 33% of patients, but on average declined 0.4 logMAR
      units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate
      of visual acuity decline was predicted weakly by tumor volume at presentation
      (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by
      visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001).
      CONCLUSIONS: Systemic chemotherapy arrested the decline in visual acuity and
      stabilized vision on average for 5 years. At presentation, VEPs were a more
      sensitive indicator of optic pathway damage than visual acuity or optic nerve
      appearance. Although tumor reduction or stabilization was achieved in 80% of
      patients, pre-existing visual damage, indexed by objective measures of tumor
      volume and visual function, limited visual outcomes. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 22364862
TI  - Stalk cell phenotype depends on integration of Notch and Smad1/5 signaling
      cascades.
AB  - Gradients of vascular endothelial growth factor (VEGF) induce single endothelial
      cells to become leading tip cells of emerging angiogenic sprouts. Tip cells then
      suppress tip-cell features in adjacent stalk cells via Dll4/Notch-mediated
      lateral inhibition. We report here that Smad1/Smad5-mediated BMP signaling
      synergizes with Notch signaling during selection of tip and stalk cells.
      Endothelium-specific inactivation of Smad1/Smad5 in mouse embryos results in
      impaired Dll4/Notch signaling and increased numbers of tip-cell-like cells at the
      expense of stalk cells. Smad1/5 downregulation in cultured endothelial cells
      reduced the expression of several target genes of Notch and of other stalk-cell
      enriched transcripts (Hes1, Hey1, Jagged1, VEGFR1, and Id1-3). Moreover, Id
      proteins act as competence factors for stalk cells and form complexes with Hes1,
      which augment Hes1 levels in the endothelium. Our findings provide in vivo
      evidence for a regulatory loop between BMP/TGFbeta-Smad1/5 and Notch signaling
      that orchestrates tip- versus stalk-cell selection and vessel plasticity.

PMID- 22364865
TI  - Preservation of posterior mandibular extraction site with allogeneic
      demineralized, freeze-dried bone matrix and calcium sulphate graft binder before
      eventual implant placement: a case series.
AB  - OBJECTIVE: This case series reports short- and long-term healing, before and
      after placement of an implant, in posterior mandibular extraction sites grafted
      with demineralized, freeze-dried bone matrix (DFDBM) allograft mixed with calcium
      sulphate graft binder. METHODS: Three patients who underwent surgical extraction
      of a posterior mandibular molar experienced partial loss of the buccal bone plate
      at the extraction site. Alveolar bone reconstruction with a DFDBM allograft mixed
      with calcium sulphate graft binder was performed immediately. The graft was
      covered with a biodegradable regenerative membrane. For each of the 3 patients,
      the implant and healing abutment were placed after 6, 9 and 12 months,
      respectively, followed by crown placement 3, 5 and 5 months later, respectively.
      The implants were periodically re-evaluated, both clinically and
      radiographically, between 10 and 39 months after final insertion of the crown. An
      implant stability device was used to evaluate the long-term biological and
      functional stability of the implants. RESULTS: Upon exposure and implant
      placement, the grafted alveolar ridge in all patients presented appropriately
      sized, dense and well-vascularized bone, wide enough to receive the planned wide
      platform implant. The long-term interface stability quotient ranged from 87 to
      90. CONCLUSIONS: Posterior mandibular extraction sites with compromised buccal
      alveolar bone may be effectively managed by immediate alveolar augmentation using
      a mixture of DFDBM allograft and calcium sulphate graft binder. This approach
      provides ideal alveolar form and consistency for eventual placement of the
      implant.

PMID- 22364866
TI  - Oral health status of long-term care residents-a vulnerable population.
AB  - OBJECTIVE: To conduct an observational, cross-sectional survey of the oral health
      status of adults >= 45 years of age in rural and urban long-term care (LTC)
      facilities in Nova Scotia, Canada. METHODS: Residents capable of informed consent
      were recruited by LTC staff in a stratified random sample of LTC facilities.
      Calibrated personnel administered standard clinical and quality-of-life
      instruments. RESULTS: Of the 335 adults (74% female) surveyed (mean age 80.8 +/-
      11.6 years), only 25% reported having regular dental care. Although 76% described
      their oral health as good or excellent, 41% were edentulous, 41% had some mucosal
      abnormality, 36% reported xerostomia and 25% had perceived or self-reported
      untreated dental conditions. Most mandibular dentures were nonretentive (59%) and
      almost half were unstable (49%). Among the dentate, 51% had untreated coronal
      caries, 44% had untreated root caries and 67% had attachment loss of >= 4 mm at
      >= 1 site. Predictors of coronal decay were a debris score >= 2 (adjusted odds
      ratio [adj OR] = 2.12; p = 0.045) or a history of smoking (adj OR = 1.02 per year
      of smoking; p = 0.024). Predictors of root caries were participants' perceiving a
      need for dental treatment (adj OR = 2.56; p = 0.015) or a history of smoking (adj
      OR = 1.02 per year of smoking; p = 0.026). CONCLUSIONS: This epidemiologic study
      of the oral health of LTC residents revealed a high prevalence of untreated oral
      disease and low use of oral care services, highlighting the need for better
      access to oral care for this population.

PMID- 22364867
TI  - Assessment of Medicare's imaging efficiency measure for emergency department
      patients with atraumatic headache.
AB  - STUDY OBJECTIVE: Computed tomography (CT) use has increased rapidly, raising
      concerns about radiation exposure and cost. The Centers for Medicare & Medicaid
      Services (CMS) developed an imaging efficiency measure (Outpatient Measure 15 [OP
      15]) to evaluate the use of brain CT in the emergency department (ED) for
      atraumatic headache. We aim to determine the reliability, validity, and accuracy
      of OP-15. METHODS: This was a retrospective record review at 21 US EDs. We
      identified 769 patient visits that CMS labeled as including an inappropriate
      brain CT to identify clinical indications for CT and reviewed the 748 visits with
      available records. The primary outcome was the reliability of OP-15 as determined
      by CMS from administrative data compared with medical record review. Secondary
      outcomes were the measure's validity and accuracy. Outcome measures were defined
      according to the testing protocol of the American Medical Association's Physician
      Consortium for Performance Improvement. RESULTS: On record review, 489 of 748 ED
      brain CTs identified as inappropriate by CMS had a measure exclusion documented
      that was not identified by administrative data; the measure was 34.6% reliable
      (95% confidence interval [CI] 31.2% to 38.0%). Among the 259 patient visits
      without measure exclusions documented in the record, the measure's validity was
      47.5% (95% CI 41.4% to 53.6%), according to a consensus list of indications for
      brain CT. Overall, 623 of the 748 ED visits had either a measure exclusion or a
      consensus indication for CT; the measure's accuracy was 16.7% (95% CI 14% to
      19.4%). Hospital performance as reported by CMS did not correlate with the
      proportion of CTs with a documented clinical indication (r=-0.11; P=.63).
      CONCLUSION: The CMS imaging efficiency measure for brain CTs (OP-15) is not
      reliable, valid, or accurate and may produce misleading information about
      hospital ED performance.

PMID- 22364868
TI  - Ramsay Hunt syndrome.
AB  - INTRODUCTION: Ramsay Hunt syndrome is a viral infection that combines facial
      palsy and pinnal vesicular rash. OBJECTIVES: To detail diagnostic criteria,
      treatment and prognosis in Ramsay Hunt syndrome. PATIENTS AND METHODS: A
      retrospective study of 15 patients with Ramsay Hunt syndrome admitted to the ENT
      department of La Rabta Hospital (Tunis) from 2003 to 2009. RESULTS: The main
      presenting symptom was facial palsy associated with conchal vesicular rash. House
      Brackmann classification of facial nerve function ranged from III to V. All
      patients were treated with acyclovir and corticosteroids. Mean follow-up was 8
      months. Ten patients showed improvement in facial palsy, four had permanent palsy
      and one moved from grade IV to grade III. CONCLUSION: Ramsay Hunt syndrome
      involves severe dysfunction, with poorer facial nerve prognosis than in Bell's
      palsy.

PMID- 22364869
TI  - First diagnostic criteria for atopic myelitis with special reference to
      discrimination from myelitis-onset multiple sclerosis.
AB  - OBJECTIVE: To establish the first evidence-based diagnostic criteria for atopic
      myelitis (AM) enabling it to be discriminated from myelitis-onset multiple
      sclerosis (MS), which is a difficult differential diagnosis. METHODS: Sixty-nine
      consecutive AM patients examined from 1996 to 2010 at Kyushu University hospital,
      who fulfilled the empirical definition of AM (2003), and 51 myelitis-onset MS
      patients in whom allergen-specific IgE was measured, were enrolled. The first
      available brain MRI findings were compared between the two. Then, we compared the
      clinical and laboratory features between the 16 AM cases who did not meet the
      Barkhof brain MRI criteria for MS after more than 5 years follow-up and 51
      myelitis-onset MS cases. Based on the discriminative findings, we established
      diagnostic criteria for AM and calculated the sensitivity and specificity.
      RESULTS: AM patients had a significantly lower frequency of Barkhof brain lesions
      on baseline MRI than myelitis-onset MS patients. AM patients had a significantly
      higher frequency of present and/or past history of atopic disease and
      hyperIgEemia, and higher cerebrospinal fluid levels of interleukin 9 and
      CCL11/eotaxin, but a lower frequency of oligoclonal IgG bands than myelitis-onset
      MS patients. Our proposed diagnostic criteria for AM demonstrated 93.3%
      sensitivity and 93.3% specificity for AM against myelitis-onset MS, with 82.4%
      positive predictive value and 97.7% negative predictive value. CONCLUSION: Our
      first evidence-based criteria for AM show high sensitivity and specificity, and
      would be useful clinically.

PMID- 22364870
TI  - [Answers to residentship reforms in obstetrics and gynaecology: what new
      education means?].

PMID- 22364872
TI  - New insights into the regulation of Na+,K+-ATPase by ouabain.
AB  - Cardiac glycosides have been widely used in the treatment of congestive heart
      failure and cardiac arrhythmias. The mechanism of their positive ionotropic
      effect is well characterized and is based on the inhibition of Na(+),K(+)-ATPase.
      However, recently it has been discovered that circulating endogenous cardiotonic
      steroids bind to Na(+),K(+)-ATPase, activate cell signaling pathways, and
      regulate diverse cellular functions. Thus, they play an important role in both
      physiological and pathological processes. Circulating endogenous ouabain has been
      reported to activate several signaling pathways upon binding to Na(+),K(+)
      ATPase, and altered plasma levels of this endogenous cardiotonic steroid have
      been found in several pathologies. This review focuses on ouabain-mediated
      activation of cell signaling pathways and secondary messengers that conversely
      may modulate Na(+),K(+)-ATPase function.

PMID- 22364873
TI  - Ciliary and flagellar structure and function--their regulations by
      posttranslational modifications of axonemal tubulin.
AB  - Eukaryotic cilia and flagella are evolutionarily conserved microtubule-based
      organelles protruding from the cell surface. They perform dynein-driven beating
      which contributes to cell locomotion or flow generation. They also play important
      roles in sensing as cellular antennae, which allows cells to respond to various
      external stimuli. The main components of cilia and flagella, alpha- and beta
      tubulins, are known to undergo various posttranslational modifications (PTMs),
      including phosphorylation, palmitoylation, tyrosination/detyrosination, Delta2
      modification, acetylation, glutamylation, and glycylation. Recent identification
      of tubulin-modifying enzymes, especially tubulin tyrosine ligase-like proteins
      which perform tubulin glutamylation and glycylation, has demonstrated the
      importance of tubulin modifications for the assembly and functions of cilia and
      flagella. In this chapter, we review recent work on PTMs of ciliary and flagellar
      tubulins in conjunction with discussing the basic knowledge.

PMID- 22364874
TI  - New insights into the regulation of epithelial-mesenchymal transition and tissue
      fibrosis.
AB  - Tissue fibrosis often presents as the final outcome of chronic disease and is a
      significant cause of morbidity and mortality worldwide. Fibrosis is driven by
      continuous expansion of fibroblasts and myofibroblasts. Epithelial-mesenchymal
      transition (EMT) is a form of cell plasticity in which epithelia acquire
      mesenchymal phenotypes and is increasingly recognized as an integral aspect of
      tissue fibrogenesis. In this review, we describe recent insight into the
      molecular and cellular factors that regulate EMT and its underlying signaling
      pathways. We also consider how mechanical cues from the microenvironment affect
      the regulation of EMT. Finally, we discuss the role of EMT in fibrotic diseases
      and propose approaches for detecting and treating fibrogenesis by targeting EMT.

PMID- 22364876
TI  - Mechanism of function of viral channel proteins and implications for drug
      development.
AB  - Viral channel-forming proteins comprise a class of viral proteins which, similar
      to their host companions, are made to alter electrochemical or substrate
      gradients across lipid membranes. These proteins are active during all stages of
      the cellular life cycle of viruses. An increasing number of proteins are
      identified as channel proteins, but the precise role in the viral life cycle is
      yet unknown for the majority of them. This review presents an overview about
      these proteins with an emphasis on those with available structural information. A
      concept is introduced which aligns the transmembrane domains of viral channel
      proteins with those of host channels and toxins to give insights into the
      mechanism of function of the viral proteins from potential sequence identities. A
      summary of to date investigations on drugs targeting these proteins is given and
      discussed in respect of their mode of action in vivo.

PMID- 22364877
TI  - Report on 2nd Royan Institute International Summer School on developmental
      biology and stem cells Tehran, Iran, 17-22nd July 2011.
AB  - The 2nd Royan Institute International Summer School was built around the topic of
      stem cells and grounding in the discipline of developmental biology. The meeting
      provided not only direct transfer of technical and intellectual information, the
      normal process in scientific meetings, but was also a forum for the exchange of
      personal ideas of science as a creative pursuit. This summer school introduced
      aspiring young Iranian scientists to international researchers and exposed the
      latter to a rich culture that highly values learning and education, attested by
      the confident, intelligent young men and women who asked probing questions and
      who were eager to participate in the workshops. Hossein Baharvand's dedication
      and passion for science have led to an impressive record of national and
      international peer-reviewed publications and an increasing number of students who
      pursue science in Iran, and shows how the right people can create an environment
      where good science, good science education and motivation will flourish. This
      report summarizes some of the activities of the workshop in the Royan Institute
      and the impressions of the visiting scientists in the wider context of the
      scientific and cultural heritage of Iran.

PMID- 22364875
TI  - Cellular and molecular biology of optineurin.
AB  - Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other
      neurodegenerative diseases, and Paget's disease of bone. This review describes
      the characteristics of optineurin and summarizes the cellular and molecular
      biology investigations conducted so far on optineurin. Data from a number of
      laboratories indicate that optineurin is a cytosolic protein containing 577 amino
      acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin,
      transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic
      cellular functions including protein trafficking, maintenance of the Golgi
      apparatus, as well as NF-kappaB pathway, antiviral, and antibacteria signaling.
      Mutation or alteration of homeostasis of optineurin (such as overexpression or
      knockdown) results in adverse consequences in the cells, leading to the
      development of neurodegenerative diseases including glaucoma.

PMID- 22364878
TI  - Nuclear cardiac troponin and tropomyosin are expressed early in cardiac
      differentiation of rat mesenchymal stem cells.
AB  - Nuclear actin - which is immunologically distinct from cytoplasmic actin - has
      been documented in a number of differentiated cell types, and cardiac isoforms of
      troponin I (cTnI) and troponin T (cTnT) have been detected in association with
      nuclei of adult human cardiac myocytes. It is not known whether these and related
      proteins are present in undifferentiated stem cells, or when they appear in
      cardiomyogenic cells following differentiation. We first tested the hypothesis
      that nuclear actin and cardiac isoforms of troponin C (cTnC) and tropomyosin
      (cTm) are present along with cTnI and cTnT in nuclei of isolated, neonatal rat
      cardiomyocytes in culture. We also tested the hypothesis that of these five
      proteins, only actin is present in nuclei of multipotent, bone marrow-derived
      mesenchymal stem cells (BM-MSCs) from adult rats in culture, but that cTnC, cTnI,
      cTnT and cTm appear early and uniquely following cardiomyogenic differentiation.
      Here we show that nuclear actin is present within nuclei of both ventricular
      cardiomyocytes and undifferentiated, multipotent BM-MSCs. We furthermore show
      that cTnC, cTnI, cTnT and cTm are not only present in myofilaments of ventricular
      cardiomyocytes in culture but are also within their nuclei; significantly, these
      four proteins appear between days 3 and 5 in both myofilaments and nuclei of BM
      MSCs treated to differentiate into cardiomyogenic cells. These observations
      indicate that cardiac troponin and tropomyosin could have important cellular
      function(s) beyond Ca(2+)-regulation of contraction. While the roles of nuclear
      associated actin, troponin subunits and tropomyosin in cardiomyocytes are not
      known, we anticipate that the BM-MSC culture system described here will be useful
      for elucidating their function(s), which likely involve cardiac-specific, Ca(2+)
      dependent signaling in the nucleus.

PMID- 22364879
TI  - Differentiation of Caco-2 cells requires both transcriptional and post
      translational down-regulation of Myc.
AB  - Caco-2 cancer cell line is widely used to reproduce in vitro the differentiation
      of absorptive enterocytes of human intestinal epithelium. This cell line, when
      cultured over confluence for 21 days, spontaneously undergoes cell cycle arrest
      and differentiates with the formation of a polarized enterocyte-like monolayer.
      During this process, Myc protein is completely down-regulated, as occurs in
      normal enterocytes. Caco-2 cells differ from normal enterocytes for mutations of
      APC and beta-catenin genes, factors known to be involved in the transcriptional
      control of MYC gene during enterocyte differentiation. In this paper, we
      investigated how Myc regulation could be achieved during Caco-2 differentiative
      process, notwithstanding the APC and beta-catenin mutations. We highlighted the
      post translational regulation of Myc protein as one of the essential mechanisms
      that allows the exit from cell cycle and onset of differentiation of Caco-2
      cells. Moreover, we found a strong correlation between Myc protein downregulation
      and the expression of the transcription factor Cdx2, suggesting the existence of
      a regulative link between these two proteins.

PMID- 22364880
TI  - Integration potential of mouse and human bone marrow-derived mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) are a multipotent cell population which has been
      described to exert renoprotective and regenerative effects in experimental models
      of kidney injury. Several lines of evidence indicate that MSCs also have the
      ability to contribute to nephrogenesis, suggesting that the cells can be employed
      in stem cell-based applications aimed at de novo renal tissue generation. In this
      study we re-evaluate the capacity of mouse and human bone marrow-derived MSCs to
      contribute to the development of renal tissue using a novel method of embryonic
      kidney culture. Although MSCs show expression of some genes involved in renal
      development, their contribution to nephrogenesis is very limited in comparison to
      other stem cell types tested. Furthermore, we found that both mouse and human
      MSCs have a detrimental effect on the ex vivo development of mouse embryonic
      kidney, this effect being mediated through a paracrine action. Stimulation with
      conditioned medium from a mouse renal progenitor population increases the ability
      of mouse MSCs to integrate into developing renal tissue and prevents the negative
      effects on kidney development, but does not appear to enhance their ability to
      undergo nephrogenesis.

PMID- 22364871
TI  - Cellular functions of tissue transglutaminase.
AB  - Transglutaminase 2 (TG2 or tissue transglutaminase) is a highly complex
      multifunctional protein that acts as transglutaminase, GTPase/ATPase, protein
      disulfide isomerase, and protein kinase. Moreover, TG2 has many well-documented
      nonenzymatic functions that are based on its noncovalent interactions with
      multiple cellular proteins. A vast array of biochemical activities of TG2
      accounts for its involvement in a variety of cellular processes, including
      adhesion, migration, growth, survival, apoptosis, differentiation, and
      extracellular matrix organization. In turn, the impact of TG2 on these processes
      implicates this protein in various physiological responses and pathological
      states, contributing to wound healing, inflammation, autoimmunity,
      neurodegeneration, vascular remodeling, tumor growth and metastasis, and tissue
      fibrosis. TG2 is ubiquitously expressed and is particularly abundant in
      endothelial cells, fibroblasts, osteoblasts, monocytes/macrophages, and smooth
      muscle cells. The protein is localized in multiple cellular compartments,
      including the nucleus, cytosol, mitochondria, endolysosomes, plasma membrane, and
      cell surface and extracellular matrix, where Ca(2+), nucleotides, nitric oxide,
      reactive oxygen species, membrane lipids, and distinct protein-protein
      interactions in the local microenvironment jointly regulate its activities. In
      this review, we discuss the complex biochemical activities and molecular
      interactions of TG2 in the context of diverse subcellular compartments and
      evaluate its wide ranging and cell type-specific biological functions and their
      regulation.

PMID- 22364881
TI  - Epithelial morphogenesis of germline-derived pluripotent stem cells on
      organotypic skin equivalents in vitro.
AB  - For tissue engineering, cultivation of pluripotent stem cells on three
      dimensional scaffolds allows the generation of organ-like structures. Previously,
      we have established an organotypic culture system of skin to induce epidermal
      differentiation in adult stem cells. Multipotent stem cells are not able to
      differentiate across germinal boundaries. In contrast, pluripotent stem cells
      readily differentiate into tissues of all three germ layers. Germline-derived
      pluripotent stem cells (gPS cells) can be generated by induction of pluripotency
      in mouse unipotent germline stem cells without the introduction of exogenous
      transcription factors. In the current study, we analyzed the influence of
      organotypic culture conditions of skin on the epithelial differentiation of gPS
      cells in comparison to the well-established HM1 ES cell line. Quantitative RT-PCR
      data of the pluripotency gene Oct4 showed that gPS cells are characterized by an
      accelerated Oct4-downregulation compared to HM1 ES cells. When subjected to the
      organotypic culture conditions of skin, gPS cells formed tubulocystic structures
      lined by stratified (CK5/6(+), CK14(+), CK8/18(-)) epithelia. HM1 ES cells formed
      only small tubulocystic structures lined by simple, CK8/18(+) epithelia. BMP-4,
      an epidermal morphogen, significantly enhanced the expression of epithelial
      markers in HM1 ES cells, but did not significantly affect the formation of
      complex (squamous) epithelia in gPS cells. In HM1 ES cells the differentiation
      into squamous epithelium was only inducible in the presence of mature dermal
      fibroblasts. Both pluripotent stem cell types spontaneously differentiated into
      mesodermal, endodermal and into neuroectodermal cells at low frequency,
      underlining their pluripotent differentiation capacity. Concluding, the
      organotypic culture conditions of skin induce a multilayered, stratified
      epithelium in gPS cells, in HM1 ES cells only in the presence of dermal
      fibroblasts. Thus, our data show that differentiation protocols strongly depend
      on the stem cell type and have to be modified for each specific stem cell type.

PMID- 22364882
TI  - Characterisation of FAP-1 expression and CD95 mediated apoptosis in the A818-6
      pancreatic adenocarcinoma differentiation system.
AB  - The present study investigated the expression and localisation of FAP-1 (Fas
      associated phosphatase-1) and CD95 in a 3D differentiation model in comparison to
      2D monolayers of the pancreatic adenocarcinoma cell line A818-6. Under non
      adherent growth conditions, A818-6 cells differentiate into 3D highly organised
      polarised epithelial hollow spheres, resembling duct-like structures. A818-6
      cells showed a differentiation-dependent FAP-1 localisation. Cells grown as 2D
      monolayers revealed FAP-1 staining in a juxtanuclear cisternal position, as well
      as localisation in the nucleus. After differentiation into hollow spheres, FAP-1
      was relocated towards the actin cytoskeleton beneath the outer plasma membrane of
      polarised cells and no further nuclear localisation was observed. CD95 surface
      staining was found only in a subset of A818-6 monolayer cells, while
      differentiated hollow spheres appeared to express CD95 in all cells of a given
      sphere. We rarely observed co-localisation of CD95 and FAP-1 in A818-6 monolayer
      cells, but strong co-localisation beneath the outer plasma membrane in polarised
      cells. Analysis of surface expression by flow cytometry revealed that only a
      subset (36%) of monolayer cells showed CD95 surface expression, and after
      induction of hollow spheres, CD95 presentation at the outer plasma membrane was
      reduced to 13% of hollow spheres. Induction of apoptosis by stimulation with
      agonistic anti-CD95 antibodies, resulted in increased caspase activity in both,
      monolayer cells and hollow spheres. Knock down of FAP-1 mRNA in A818-6 monolayer
      cells did not alter resposiveness to CD95 agonistic antibodies. These data
      suggested that CD95 signal transduction was not affected by FAP-1 expression in
      A818-6 monolayer cells. In differentiated 3D hollow spheres, we found a
      polarisation-induced co-localisation of CD95 and FAP-1. A tight control of
      receptor surface representation and signalling induced apoptosis ensures
      controlled removal of individual cells instead of a "snowball effect" of
      apoptotic events.

PMID- 22364883
TI  - In search of a wide-angle perspective.

PMID- 22364884
TI  - Polymorphisms of SLC30A2 and selected perinatal factors associated with low milk
      zinc in Chinese breastfeeding women.
AB  - The variability of breast-milk zinc concentration is high among breastfeeding
      women, and it is known to be independent of dietary zinc intake. As a result,
      transient neonatal zinc deficiency is not rare in the breastfed infants due to
      low milk zinc concentration in their breastfeeding mothers. Up to now, SLC30A2
      has been documented the only candidate gene showing correlation with human milk
      zinc trait. In this study, 750 breastfeeding women were recruited and 10ml
      foremilk was collected on 42nd postpartum day. The milk zinc concentration was
      measured, and genomic DNA was isolated from breast-milk. Direct sequencing and
      Taqman assay were used to identify the SLC30A2 polymorphisms associated with low
      milk-zinc. Subsequently, the factors associated with breast-milk zinc were
      investigated using regression model. The correlation study showed that SLC30A2/
      697G>T and SLC30A2/1031A>G polymorphisms were associated with low-milk-zinc in
      our subjects. These two polymorphisms explained 3.23% of total variance in milk
      zinc level. For non-genetic variables, the obese breastfeeding women (BMI>25)
      secreted less zinc into their breast-milk. The variation of milk zinc was
      independent of pregnant age, birth weight, infant gender, cesarean delivery,
      preterm delivery and vitamin D supplementation. In conclusion, our results
      indicated that -697G>T and 1031A>G polymorphisms in the SLC30A2 gene may be
      associated with low-milk-zinc in Chinese breastfeeding women. Maternal BMI is
      significantly correlated with milk zinc level in negative manner. Our study
      demonstrated that both genetic and non-genetic factors could modulate milk zinc
      level.

PMID- 22364885
TI  - The long-term predictive validity of early motor development in "apparently
      normal" ELBW survivors.
AB  - BACKGROUND: Within the able majority of ELBW survivors, there is a lack of
      identified predictors of which children will require extra support despite having
      escaped significant disability. AIMS: Investigate the predictive validity of
      early motor scores, compared to that of perinatal descriptors or early growth, on
      long-term motor impairment in non-disabled ELBW (<1000g) children. STUDY DESIGN:
      Prospective longitudinal study. OUTCOME MEASURES: 48 non-disabled ELBW children
      (27 male) completed the Neurosensory Motor Developmental Assessment (NSMDA) at 8
      months, 2 years and 4 years post term and The Motor Assessment Battery for
      Children (MABC) at 11-13 years of age. Other possible predictors of long-term
      outcomes (gestational age, birthweight, multiple birth, head circumference
      measures and gender) were retrieved from the records. RESULTS: Early motor
      assessment (NSMDA score) independently predicted the MABC total score at 11-13
      years of age with a positive predictive value of 87% by 4 years post term. There
      was increased risk of long-term motor impairment associated with male gender but
      the degree of prematurity, multiple birth status or early growth measures did not
      predict motor outcome. Postural control and sensory motor scores at 4 years post
      term, rather than neurological score, were associated with long-term motor
      outcomes for the ELBW children at 11-13 years of age. CONCLUSIONS: Early motor
      scores are valid markers of long-term motor outcomes for "apparently normal" ELBW
      children. Early postural competence and sensory motor function are discriminating
      in regards to long-term motor function in neurologically normal ELBW children.

PMID- 22364886
TI  - Removal of parotid, submandibular, and sublingual glands.
AB  - Surgical removal of the major salivary glands is a common task for the oral and
      maxillofacial surgeon. The major salivary glands have complex anatomic
      relationships with the surrounding neurovascular structures, and a thorough
      understanding of the surgical anatomy is essential for any surgeon involved in
      the management of salivary gland disease. This article reviews the indications,
      surgical anatomy, diagnostic evaluation, and surgical techniques for removal of
      the major salivary glands.

PMID- 22364887
TI  - [Tours experience of endovascular treatment in superior vena cava syndrome].
AB  - Superior vena cava syndrome is a clinical entity including symptoms arising from
      an obstruction of return flow in the superior vena cava. It can be life
      threatening. In the context of lung cancer, by far the most prominent etiology
      (nine of ten cases in our series), the condition is particularly serious, with
      only 20% survival at one year. Medical treatment may be insufficient, requiring
      surgical salvage. Palliative procedures are rapidly effective and well tolerated.
      We perform a first intention transluminal angioplasty under local anesthesia via
      the right femoral vein. This ultrasound-guided procedure enables insertion of a
      non-coated nitinol stent. The success rate in our hands has been 90%. Clinical
      improvement is constant and immediate with long-term efficacy. The early and late
      post-operative period is uneventful.

PMID- 22364888
TI  - Population based strategy for dietary salt intake reduction: Italian initiatives
      in the European framework.
AB  - Excess dietary sodium chloride (salt) intake is etiologically related to
      hypertension and cardiovascular disease (CVD). Moderate reduction of salt intake
      reduces blood pressure (BP) and is expected to contribute to reduce the risk of
      CVD. Previous community-based trials to reduce BP by means of salt reduction were
      very successful. The initial positive results of national strategies of dietary
      salt intake reduction in several European countries, driven by the initiative of
      the World Health Organisation (WHO) and non-governmental organisations such as
      the World Action of Salt and Health (WASH), have paved the way for action in
      other European Union (EU) member states. In Italy, several initiatives aiming at
      reduction of salt intake at the population level have been recently undertaken.
      These initiatives include i) the evaluation of current dietary habits promoted by
      the Working Group for Dietary Salt Reduction in Italy (GIRCSI); ii) the chemical
      analysis of the bread salt content, a major source of sodium intake in Italy, and
      the agreement between the bakers' associations and the Ministry of Health for a
      gradual reduction of the bread salt content; iii) the implementation of
      educational campaigns to increase population awareness, iv) the involvement of
      the food catering system. In the immediate future, food reformulation must be
      extended to other food categories in collaboration with industry, foods' salt
      targets ought to be defined, the food labelling system must be improved and
      population salt awareness must be further increased through educational
      campaigns. The GIRCSI Working Group is committed to pursue these objectives.

PMID- 22364889
TI  - Glitazones in chronic kidney disease: potential and concerns.
AB  - AIMS: Glitazones rank now among the most used hypoglycemic agents in patients
      with type-2 diabetes. This systematic review focuses on the cardiovascular and
      renal outcomes in chronic kidney disease (CKD) patients treated with these drugs.
      DATA SYNTHESIS: Data from randomized clinical trials and a meta-analysis indicate
      that glitazones (particularly rosiglitazone) may increase the risk of myocardial
      infarction, heart failure and cardiovascular death in type-2 diabetics.
      Observational studies looking at survival and cardiovascular outcomes in diabetic
      patients with kidney failure show controversial results. Studies in experimental
      models and clinical studies suggest that glitazones may have favorable effects on
      renal disease progression, because these drugs coherently reduce urinary albumin
      excretion and proteinuria in diabetic and non-diabetic nephropathies. No clinical
      trial based on clinical end-points like kidney failure has until now tested the
      effect of glitazones on the evolution of chronic renal failure in these patients.
      CONCLUSIONS: Whether the use of glitazones has a positive or a negative impact
      upon major cardiovascular and renal outcomes in diabetic patients remains an
      open, unanswered question. Specific studies are needed to assess the efficacy and
      safety of glitazones in a high risk population like type-2 diabetics with chronic
      kidney disease.

PMID- 22364890
TI  - Small fiber function in drug naive patients with idiopathic restless legs
      syndrome.
AB  - To assess whether idiopathic restless legs syndrome (RLS) is associated with
      small fiber abnormalities, we evaluated somatic and autonomic small fiber
      function in 56 patients with idiopathic RLS and 36 age-matched and sex-matched
      healthy controls using quantitative sensory testing and quantitative sudomotor
      axon reflex tests. The warm detection thresholds (WDT) of the hands (p=0.017) and
      feet (p=0.008) were higher in patients with RLS than in controls. Cooling
      detection thresholds (CDT) were higher in the feet of patients with RLS than
      controls (p<0.001), but CDT in the hands did not differ between groups (p=0.161).
      There were no significant between-group differences in total sweat volume and
      sweat production in the forearms, proximal legs, distal legs, and feet (p>0.1
      each). These findings suggest that abnormal sensory perception in patients with
      idiopathic RLS may result from impairment of central somatosensory processing
      rather than small fiber neuropathy.

PMID- 22364891
TI  - Probabilistic health risk assessment of carcinogenic emissions from a MSW
      gasification plant.
AB  - Health risk assessment due to the atmospheric emissions of carcinogenic
      pollutants (PCDD/Fs and Cd) from a waste gasification plant is performed by means
      of a probabilistic approach based on probability density functions for the
      description of the input data of the model parameters involved in the assessment.
      These functions incorporate both the epistemic and stochastic uncertainty of the
      input data (namely, the emission rate of the pollutants) and of all the
      parameters used for individual exposure assessment through the pathways of
      inhalation, soil ingestion and dermal contact, and diet. The uncertainty is
      propagated throughout the evaluation by Monte Carlo technique, resulting in the
      probability distribution of the individual risk. The median risk levels nearby
      the plant are in the 10(-8)-10(-10) range, ten-fold lower than the deterministic
      estimate based on precautionary values for the input data; however, the very
      upper percentiles (>95th) of the risk distribution can exceed the conventional
      10(-6) reference value. The estimated risk is almost entirely determined by the
      Cd exposure through the diet; the pathways arising from PCDD/Fs exposure are
      without any practical significance, suggesting that the emission control should
      focus on Cd in order to reduce the carcinogenic risk. Risk variance decomposition
      shows the prevailing influence on the estimated risk of the Cd concentration at
      the emission stack: thus, for a more accurate risk assessment the efforts should
      focus primarily on the definition of its probability density function.

PMID- 22364892
TI  - Facing depression with botulinum toxin: a randomized controlled trial.
AB  - Positive effects on mood have been observed in subjects who underwent treatment
      of glabellar frown lines with botulinum toxin and, in an open case series,
      depression remitted or improved after such treatment. Using a randomized double
      blind placebo-controlled trial design we assessed botulinum toxin injection to
      the glabellar region as an adjunctive treatment of major depression. Thirty
      patients were randomly assigned to a verum (onabotulinumtoxinA, n = 15) or
      placebo (saline, n = 15) group. The primary end point was change in the 17-item
      version of the Hamilton Depression Rating Scale six weeks after treatment
      compared to baseline. The verum and the placebo groups did not differ
      significantly in any of the collected baseline characteristics. Throughout the
      sixteen-week follow-up period there was a significant improvement in depressive
      symptoms in the verum group compared to the placebo group as measured by the
      Hamilton Depression Rating Scale (F((6,168)) = 5.76, p < 0.001, eta(2) = 0.17).
      Six weeks after a single treatment scores of onabotulinumtoxinA recipients were
      reduced on average by 47.1% and by 9.2% in placebo-treated participants
      (F((1,28)) = 12.30, p = 0.002, eta(2) = 0.31, d = 1.28). The effect size was even
      larger at the end of the study (d = 1.80). Treatment-dependent clinical
      improvement was also reflected in the Beck Depression Inventory, and in the
      Clinical Global Impressions Scale. This study shows that a single treatment of
      the glabellar region with botulinum toxin may shortly accomplish a strong and
      sustained alleviation of depression in patients, who did not improve sufficiently
      on previous medication. It supports the concept, that the facial musculature not
      only expresses, but also regulates mood states.

PMID- 22364893
TI  - Blood levels of dioxins, furans, dioxin-like PCBs, and TEQs in general
      populations: a review, 1989-2010.
AB  - A comprehensive worldwide literature review of blood levels of dioxins and dioxin
      like compounds in non-exposed adult general populations was performed. The
      studies published in 1989-2010 reporting information on polychlorinated dibenzo
      para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho-PCBs
      (nPCBs), mono-ortho-PCBs (mPCBs) levels and Toxic Equivalencies (TEQs, a summary
      weighted measure of their combined toxicity) were reviewed. TEQs were calculated
      using as standard the most recent WHO 2005 reevaluation of Toxic Equivalency
      Factors (TEFs). Weighted multiple regression analyses adjusted for year,
      subject's age, type of sample analyzed, method used for values below detection
      limit, and central tendency measure used were performed for each congener and
      standardized TEQs (log-transformed). We identified 187 studies regarding 29,687
      subjects of 26 countries. Year of blood collection ranged from 1985 to 2008. The
      studies reporting congener levels 161. In adjusted analyses, European countries
      showed higher levels of most dioxin-like congeners and TEQs. A strong positive
      association of subjects' age with most congeners and with TEQ values was found,
      confirming previous findings. Significant decreases over time (1985-2008) were
      documented for PCCDs, PCDFs, and TEQs including their contributions. No
      significant decrease was found for non-ortho-PCBs, notably PCB 126. Only some
      mono-ortho-PCBs showed clear significant declines. Accordingly, TEQs including
      only PCB contribution did not decrease over time. In interpreting these findings,
      it should be considered that for dioxin-like PCBs the analysis period was shorter
      (17 years), since these compounds were first measured in 1992.

PMID- 22364895
TI  - Residual valve and stricture after posterior urethral valve ablation: how to
      evaluate?
AB  - OBJECTIVE: To investigate the clinical and radiological parameters of posterior
      urethral valve (PUV) patients with residual valve or strictures after primary
      valve ablation. PATIENTS AND METHODS: A total of 127 PUV patients were treated in
      our clinic between 1986 and 2009. We retrospectively reviewed the records of 101
      patients, who had at least 1 year of follow-up data, regarding the presence of
      valve remnants or urethral strictures after PUV ablation. RESULTS: A total of 21
      patients (20.8%) underwent repeat-urethroscopy and, of these, residual valve
      leaflets or stricture were detected in 10 patients (10/101, 9.9%). In 2 of these
      10 (20%), the urethra had been found to be normal on the first voiding
      cystourethrogram following ablation. However, these two boys underwent re
      urethroscopy due to persistent vesicoureteral reflux in one and persistent
      hydroureteronephrosis in the other, and valve remnants were detected. The
      remaining 8 cases had radiological signs consistent with persistent infravesical
      obstruction in the early period. Obstruction was due to urethral stricture and
      residual valve remnants in 2 and 6 cases, respectively. CONCLUSIONS: There was
      clinical suspicion of residual valve in about 20% of the cases and in half of
      these the urethra was found to be normal on urethroscopy. The possible presence
      of residual valve remnants after primary valve ablation should be confirmed by
      careful clinical, radiological and endoscopic evaluation.

PMID- 22364894
TI  - Long-term impact of radial artery harvest on forearm function and symptoms: a
      comparison with leg vein.
AB  - OBJECTIVE: The radial artery (RA) has gained popularity as a conduit for coronary
      artery bypass surgery despite a paucity of patient-centered analysis of long-term
      quality of life after its removal. We sought to characterize forearm function and
      symptoms after RA harvest and compare these with those associated with saphenous
      vein (SV) removal. METHODS: A total of 408 patients from an RA trial completed a
      questionnaire up to 14 years after primary coronary artery bypass surgery. The
      survey included 7 statements concerning hand and forearm symptoms or limitations
      in daily life and 4 questions on concerns associated with arm or leg scars. A
      total of 230 patients had received an RA graft (RA group). Responses were graded
      in order of severity from 0 to 7, with greater than 3 (mild concern) being
      regarded as a significant symptom. Mean response to each question and total
      scores were compared with the non-RA harvest group. Comparisons were also made
      with responses to the same questionnaire completed preoperatively and 3 months
      postoperatively. In patients who had both RA and SV removal, we compared the
      impact of a forearm scar on quality of life with that of a leg scar. RESULTS: The
      mean duration of follow-up was 9.3 years (range, 4-14 years), and the response
      rate was 83%. In the RA group, 92% to 99% reported no significant symptoms, with
      the most frequent concerns relating to pain and numbness (8% each), but this was
      not significantly higher than in those who had not had an RA harvested. In the RA
      group, the mean scores for scar appearance and discomfort were 0.95 and 0.93,
      respectively (where 1 = no concern), suggesting satisfactory cosmesis and no
      impact on function. Symptom severity was significantly worse in 6 of 7 questions
      when compared with preoperative responses and in 4 of 7 items compared with 3
      month follow-up, indicating a general deterioration in function over long-term
      follow-up. In those who had both the RA and SV harvested, patients reported more
      scar discomfort associated with SV harvest at 3 months (1.69 vs 1.34, P < .001)
      and in the present questionnaire (1.21 vs 0.97, P = .002). Concerns with scar
      appearance were no different between the arm and leg. CONCLUSIONS: RA harvesting
      is associated with high patient satisfaction and less scar discomfort than SV
      removal. Overall, functionality declines with time, and a small proportion of
      patients seem to experience forearm pain and numbness. However, this is not
      different than in those without artery removal and may therefore be unrelated to
      the effects of surgery.

PMID- 22364896
TI  - Quantification of superparamagnetic iron oxide with large dynamic range using
      TurboSPI.
AB  - This work proposes the use of TurboSPI, a multi-echo single point imaging
      sequence, for the quantification of labeled cells containing moderate to high
      concentrations of iron oxide contrast agent. At each k-space location, TurboSPI
      acquires several hundred time points during a spin echo, permitting reliable
      relaxation rate mapping of large-R(2)(*) materials. An automatic calibration
      routine optimizes image quality by promoting coherent alignment of spin and
      stimulated echoes throughout the multi-echo train, and this calibration is
      sufficiently robust for in vivo applications. In vitro relaxation rate
      measurements of SPIO-loaded cervical cancer cells exhibit behavior consistent
      with theoretical predictions of the static dephasing regime in the spin echo
      case; the relaxivity measured with TurboSPI was 10.47+/-2.3 s(-1)/mG, comparable
      to the theoretical value of 10.78 s(-1)/mG. Similar measurements of micron-sized
      iron oxide particles (0.96 MUm and 1.63 MUm diameter) show a reduced relaxivity
      of 8.06+/-0.68 s(-1)/mG and 7.13+/-0.31 s(-1)/mG respectively, indicating that
      the static dephasing criterion was not met. Nonetheless, accurate quantification
      of such particles is demonstrated up to R(2)(*)=900 s(-1), with a potentially
      higher upper limit for loaded cells having a more favorable R(2)('):R(2) ratio.
      Based on the cells used in this study, reliable quantification of cells loaded
      with 10 pg of iron per cell should be possible up to a density of 27 million
      cells/mL. Such quantification will be of crucial importance to the development of
      longitudinal monitoring for cellular therapy and other procedures using iron
      labeled cells.

PMID- 22364897
TI  - Feeding skill milestones of preterm infants born with extremely low birth weight
      (ELBW).
AB  - AIM: To compare the feeding development of preterm infants with that of full-term
      infants. PARTICIPANTS: Nineteen preterm infants with extremely low birth weight,
      and 11 healthy full-term infants. METHODS: Intensive follow-up study. Feeding
      situations were analyzed by NOMAS (Neonatal Oral Motor Assessment Scale) and by
      an oral motor patterns checklist based on video recorded sessions. RESULTS: Most
      of the preterm infants showed a disorganized sucking pattern and most of the full
      term infants a normal sucking pattern, as long as suckling was present. However,
      the early suckling pattern did not predict the schedule of later feeding
      development. Preterm infants seemed to learn the various feeding skills at the
      same corrected ages as full-term infants, with the exception of munching, which
      they learned earlier than the full-term infants. However, the age range for
      gaining these skills was wider for the preterm infants. Preterm infants also
      seemed to have feeding problems more often than full-term infants when
      qualitative features of feeding were considered. Feeding was prolonged and messy,
      and the preterm infants were sensitive to different qualities of food.
      CONCLUSION: Feeding development of preterm and full-term infants is similar
      except for suckling, when only oral motor skills are concerned. When the
      qualitative characteristics of feeding are taken into account, the preterm
      infants suffer from feeding problems that create a risk for early interaction and
      communication.

PMID- 22364898
TI  - Postoperative lymphocysts after lymphadenectomy for gynaecological malignancies:
      preventive techniques and prospects.
AB  - Postoperative lymphocyst formation is an insufficiently recognised complication
      of lymphadenectomy for gynaecological malignancies. Lymphocysts are collections
      of lymph organised into cysts that develop in contact with lymphadenectomy
      compartments. There has been considerable debate about the relevance of
      lymphocyst prevention using surgical or pharmacotherapeutic methods. Here, we
      review the available studies about the impact of these methods on the incidence
      of lymphocysts. This review suggests that several techniques may decrease the
      incidence of lymphocysts when used in combination. On a literature basis, the
      peritoneum should be left open over the lymphadenectomy sites at the end of the
      procedure and drains should not be placed at the end of the procedure.
      Omentoplasty should be encouraged and further studies are needed to assess the
      potential benefits of new energies. Postoperative octreotide therapy seems
      beneficial but the role of this drug in pelvic oncological surgery remains to be
      determined.

PMID- 22364899
TI  - William H. Harridge Memorial Lecture. Changing the surgical education paradigm
      for the 21st century.

PMID- 22364900
TI  - Biplanar flap reconstruction for pressure ulcers: experience in patients with
      immobility from chronic spinal cord injuries.
AB  - BACKGROUND: Surgical therapy for advanced-stage pressure ulcers recalcitrant to
      healing is a widely accepted practice. The present study examined the incidence
      of wound recurrence after reconstruction with fasciocutaneous versus combined
      (biplanar) muscle and fasciocutaneous flaps. METHODS: A retrospective review
      identified 90 nonambulatory patients with spinal cord injury who underwent
      reconstruction for persistent decubitus ulcers from 2002 to 2008. Electronic
      medical records were surveyed for patient comorbidities and postoperative
      complications. Statistical methods included the Fisher exact test and the Mann
      Whitney U test with a 2-sided P value of less than .05. RESULTS: Among 90
      patients reviewed, 33% (n = 30) received fasciocutaneous flaps and 66% (n = 60)
      underwent biplanar reconstruction. Comorbidities were the same between cohorts
      with the exception of a greater prevalence of diabetes in the biplanar group (27%
      vs 50%; P < .05). The incidence of recurrence for biplanar flaps (25%) was
      significantly lower than for fasciocutaneous reconstruction (53%; P < .01).
      CONCLUSIONS: Biplanar flap reconstruction should be considered for chronically
      immobilized patients at high risk for recurrent decubitus ulceration.

PMID- 22364902
TI  - Does resident involvement effect surgical times and complication rates during
      laparoscopic appendectomy for uncomplicated appendicitis? An analysis of 16,849
      cases from the ACS-NSQIP.
AB  - BACKGROUND: Controversy exists regarding whether resident involvement during
      surgery impacts patient outcomes. We compared surgical times and perioperative
      complications of patients undergoing laparoscopic appendectomy with and without
      residents. METHODS: Patients undergoing laparoscopic appendectomy for
      uncomplicated acute appendicitis during 2005 to 2008 were identified from the
      American College of Surgeons National Surgical Quality Improvement Program
      database. RESULTS: During the study period, 16,849 patients underwent
      laparoscopic appendectomy for uncomplicated appendicitis (residents participated
      in 68% of procedures). There were no statistical and/or clinically meaningful
      differences between median age, sex, body mass index, American Society of
      Anesthesiology score, and morbidity probability between the 2 groups, suggesting
      that case mix was not a significant confounder. Patients undergoing laparoscopic
      appendectomy with residents compared with patients undergoing laparoscopic
      appendectomy without residents had a higher incidence of serious and overall
      morbidity and longer surgical times. However, surgical times and complications
      were similar between residents in postgraduate years 1 to 5. CONCLUSIONS:
      Regardless of the postgraduate year level, resident involvement resulted in a
      clinically appreciable increase in surgical times and a statistically significant
      increase in certain complications.

PMID- 22364901
TI  - Outcomes using a bioprosthetic mesh at the time of permanent stoma creation in
      preventing a parastomal hernia: a value analysis.
AB  - PURPOSE/METHODS: A retrospective review of the medical records of all patients
      who had a prosthetic placed at the time of stoma creation for the prevention of a
      parastomal hernia was performed. The purpose of this study was to evaluate the
      safety, efficacy, and cost-effectiveness of bioprosthetics. RESULTS: A
      bioprosthetic was used in 16 patients to prevent the occurrence of a parastomal
      hernia. The median follow-up was 38 months. There were no mesh-related
      complications, and no parastomal hernias occurred. On value analysis, to be cost
      effective, the percentage of patients who would have subsequently needed surgical
      repair of a parastomal hernia would have to be in excess of 39% or the
      bioprosthetic would have to cost less than $2,267 to $4,312. CONCLUSIONS: These
      data show the safety and efficacy of using a bioprosthetic at the time of
      permanent stoma creation in preventing a parastomal hernia and defines the
      parameters for this approach to be cost-effective.

PMID- 22364903
TI  - Does a history of wound infection predict postoperative surgical site infection
      after ventral hernia repair?
AB  - BACKGROUND: Stratification of risks of postoperative wound/mesh infection after
      hernia repair remains a challenge. We aimed to determine the role of a previous
      wound infection on surgical site infection in patients undergoing open ventral
      hernia repair. METHODS: All patients undergoing open ventral hernia repair in a
      clean setting were evaluated from a prospectively maintained database. The
      primary end point was the development of a postoperative surgical site infection.
      RESULTS: A total of 146 patients were included in the analysis, and 22 patients
      had a history of previous wound infection. The rate of surgical site infection
      did not differ between those with or without a history of wound infection (14% vs
      9%; P = .444). Patients with a history of chronic obstructive pulmonary disease
      or smoking were at an increased risk of developing a surgical site infection.
      CONCLUSIONS: For patients undergoing open ventral hernia repair, a history of
      previous wound infection is not predictive of postoperative surgical site
      infection.

PMID- 22364904
TI  - Outcomes of ileocolic resection and right hemicolectomies for Crohn's patients in
      comparison with non-Crohn's patients and the impact of perioperative
      immunosuppressive therapy with biologics and steroids on inpatient complications.
AB  - BACKGROUND: The purpose of this study was to compare medication use and
      complication rates between Crohn's disease (CD) and non-CD patients undergoing
      ileocolic resections and right hemicolectomies. METHODS: A review of patients who
      underwent ileocolic resections and right hemicolectomies from January 1, 2003,
      through December 31, 2010, was performed. Data collected included demographics
      and clinical information, biologics use (eg, infliximab, adalimumab), other
      medication use (eg, steroids), complications, and mortality. RESULTS: There were
      791 records reviewed, with 93 CD patients. There was no significant difference in
      major or minor complications, anastomotic leaks, operating room time, or
      postoperative ileus occurrence between the CD and non-CD groups (P > .05). Use of
      biologics and steroids were significantly higher among the CD patients.
      Mortality, age, and American Society of Anesthesiologists score were
      significantly higher in the non-CD group. CONCLUSIONS: Ileocolic resections and
      right hemicolectomies in CD patients are not associated with an increase in
      complication rates even when the patients use steroids and biologics in the
      preoperative period.

PMID- 22364905
TI  - Developing an experimental model for surgical drainage investigations: an initial
      report.
AB  - BACKGROUND: We sought to pilot and initiate validation of a surgical drainage
      model. METHODS: We designed a laboratory model to compare Jackson-Pratt surgical
      drains using 3 soups to emulate body fluids of serous, purulent, and necrotic
      debris. Each drain was trialed with each of the 3 fluids. Time and completeness
      of drainage were recorded. A survey of surgical residents and faculty was
      performed for convenience sampling. RESULTS: Under serous conditions, the round
      Jackson-Pratt drained the cavity quicker, but left a larger residual volume of
      fluid. Under purulent conditions, the round Jackson-Pratt was slower and drained
      less fluid. With debris fluid, the round Jackson-Pratt was quicker with less
      residual fluid whereas the flat type clogged each time. Survey results showed
      adequate concordance with surgeons in agreement on soup choice. CONCLUSIONS: The
      Jackson-Pratt drains perform differently depending on the drainage situation. The
      surgical community requires improved drain data to drive practice patterns.

PMID- 22364906
TI  - Does gender predict performance of novices undergoing Fundamentals of
      Laparoscopic Surgery (FLS) training?
AB  - BACKGROUND: This study was performed to assess the hypothesis that performance
      levels for Fundamentals of Laparoscopic Surgery (FLS) tasks were not dependent on
      trainee gender. METHODS: Initial and final task completion times for 4 FLS tasks
      performed by 132 novices (4th-year medical students and 1st-year residents) were
      collated by task type and compared by gender. RESULTS: All novices improved
      significantly with training (P > .001) on all tasks. Initial performance by men
      was better than by women but only reached significance for peg transfer and
      intracorporeal knot tying (P > .05). With training, women's performance became
      equivalent to that of men but showed a comparable or greater response to
      training. CONCLUSIONS: The gender-related differences noted in initial FLS task
      performance disappeared after training. Gender displayed no effect on FLS
      training outcomes. The use of initial FLS task performance levels, seemingly
      objective selection criteria, would introduce gender bias into the ranking
      process.

PMID- 22364907
TI  - Tibial component fixation with a peri-apatite coating: evaluation by
      radiostereometric analysis in a canine total knee arthroplasty model.
AB  - Cementless fixation for the tibial component in total knee arthroplasty (TKA)
      remains problematic. Peri-Apatite (PA), a solution-deposited hydroxyapatite, is
      under investigation as an option for improving the fixation of cementless tibial
      components. In this study, radiostereometric analysis was used to document
      implant migration in 48 dogs that underwent TKA with cementless, PA-coated, or
      cemented tibial components. Migration at 12 weeks was similar in the 2 groups. At
      12 months, there was greater migration in the PA-coated group, but the difference
      between the 2 groups was below the threshold considered clinically significant.
      In this canine TKA model, cementless fixation with PA performed less well than
      did cemented fixation, but not to a degree that would make a clinical difference
      in the short term.

PMID- 22364908
TI  - Outcomes of total hip and knee arthroplasty after cardiac transplantation.
AB  - The outcomes of 18 primary or revision total hip (THA) and knee arthroplasties
      (TKA) in 9 patients with cardiac transplants were reviewed. Primary total joint
      arthroplasties were performed for osteonecrosis (5 hips) or osteoarthritis (5
      hips, 4 knees). There were no infections in any of these patients. Final Harris
      Hip Scores were 71.8 for patients with osteonecrosis and 88.6 for osteoarthritis.
      Eight of 10 hips were pain-free at final follow-up. Two of the 10 primary THAs
      required late revision at 7 and 10 years after the index arthroplasty. One
      patient (2 hips and 1 knee) had chronic bilateral lower extremity pain. Total
      knee arthroplasty range of motion averaged from 7.5 degrees  to 118 degrees .
      Average final Knee Society function score was 79, and objective score was 88. One
      of 4 patients with primary TKA required a manipulation under anesthesia. No
      reoperations were required in this group. Overall, patients with heart
      transplantations on immunosuppression had generally good pain relief after THA
      and TKA. There were no infections in this small cohort; however, there were many
      complications.

PMID- 22364909
TI  - [Misleading improvement of abdominal tuberculosis with amikacin, within 72
      hours].

PMID- 22364910
TI  - Vaccination programs for reproductive disorders of small ruminants.
AB  - Vaccines are available for the control of contagious epididymitis and abortion in
      small ruminants, although many of them have significant limitations either in
      efficacy or safety to both the animals vaccinated and to the people handling the
      vaccine or animals. Shelf-life of vaccines should be extended and improved, so
      that the vaccine remains effective with longer term storage and ideally without
      refrigeration, so that use in under-developed rural areas is not restricted
      (e.g., Brucella melitensis, Toxoplasma gondii). The vaccines should not be
      dangerous for veterinarians or producers to handle (again as examples, B.
      melitensis, T. gondii). The vaccines should prevent shedding of the organism, in
      order to prevent spread of the disease causal agent through the sale of
      vaccinated but shedding animals (e.g., inactivated killed Chlamydophila abortus
      vaccines), as well as to prevent possible exposure to people handling those
      vaccinated animals. Production of vaccines using zoonotic disease agents is
      problematic and sometime dangerous, which increases regulatory restrictions and
      reduces availability of those vaccines (e.g., C. abortus, Coxiella burnetii).
      Development of subunit recombinant DNA vaccines may offer a method to increase
      access to these important vaccines, as long as they are also effective, prevent
      shedding and remain cost effective. It is important that these vaccines are
      brought to international commercial production. As many of these disease agents
      are zoonotic and prevalent world-wide, improvement in vaccine efficacy and safety
      is of extreme importance.

PMID- 22364911
TI  - IEP as a parameter characterizing the pH-dependent surface charging of materials
      other than metal oxides.
AB  - The numerical values of points of zero charge (PZC, obtained by potentiometric
      titration) and of isoelectric points (IEP) of various materials reported in the
      literature have been analyzed. In sets of results reported for the same chemical
      compound (corresponding to certain chemical formula and crystallographic
      structure), the IEP are relatively consistent. In contrast, in materials other
      than metal oxides, the sets of PZC are inconsistent. In view of the inconsistence
      in the sets of PZC and of the discrepancies between PZC and IEP reported for the
      same material, it seems that IEP is more suitable than PZC as the unique number
      characterizing the pH-dependent surface charging of materials other than metal
      oxides. The present approach is opposite to the usual approach, in which the PZC
      and IEP are considered as two equally important parameters characterizing the pH
      dependent surface charging of materials other than metal oxides.

PMID- 22364912
TI  - Systematic reviews: toward best practice in patient care.

PMID- 22364913
TI  - Reconstituting National Institute for Biological Standards and Control (NIBSC)
      chemokines.
AB  - We observed significant discrepancies between immunoassay results when using
      different internally prepared reference preparations for interleukin-8 (IL-8) and
      monocyte chemoattractant protein-1 (MCP-1) from the National Institute for
      Biological Standards and Control (NIBSC). To evaluate the reasons for this we
      prepared the chemokines using diluents that incorporated protein at different
      steps. This showed that even brief addition of water to these preparations, in
      the absence of additional protein, resulted in loss of immunoreactivity in
      assays. The data obtained emphasise the importance of adding protein at an early
      stage of preparation to avoid loss of material and potential loss of activity.

PMID- 22364914
TI  - Leptin and adiponectin, but not IL18, are related with insulin resistance in
      treated HIV-1-infected patients with lipodystrophy.
AB  - Leptin, adiponectin and IL18 are adipokines related with obesity, insulin
      resistance and dyslipidemia in the general population. Treated HIV-1-infected
      patients with lipodystrophy may develop insulin resistance and proatherogenic
      dyslipidemia. We assessed the relationship between plasma adipokine levels,
      adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin,
      adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected
      patients treated with antiretroviral drugs (132 with lipodystrophy and 150
      without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R,
      ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by
      sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with
      or without lipodystrophy (p<0.001 for both comparisons) and were lower in
      patients with lipodystrophy compared with those without lipodystrophy (p=0.006).
      In patients with lipodystrophy, leptin had a positive correlation with insulin
      and with HOMA-IR. Adiponectin levels were non-significantly different in UC and
      HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels
      than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy,
      adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides.
      Plasma IL18 levels were higher in HIV-1-infected patients compared with UC
      (p<0.001), and no differences were found according to the presence of
      lipodystrophy. In patients with lipodystrophy there was a negative correlation
      between IL18 levels and LDLc. Genetic analyses indicated no significant
      associations with lipodystrophy nor with insulin resistance or with lipid
      abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin
      levels. This reduction is magnified in patients with lipodystrophy whose
      adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma
      IL18 levels are increased in infected patients irrespective of the presence of
      lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy
      or metabolic disturbances in treated HIV-1-infected patients.

PMID- 22364915
TI  - The association between self-reported cardiovascular disorders and troublesome
      neck pain: a population-based cohort study.
AB  - OBJECTIVE: The purpose of this population-based cohort study was to investigate
      the association between self-reported cardiovascular disorders and troublesome
      neck pain. METHODS: Using data from the Saskatchewan Health and Back Pain Survey
      (1995), we formed a cohort of 922 randomly sampled Saskatchewan adults with no or
      mild neck pain. We used the Comorbidity Questionnaire to measure the point
      prevalence of self-reported cardiovascular disorders and classified them into 3
      levels of severity: (1) absent, (2) present but does not or mildly impacts on my
      health, and (3) present and moderately or severely impacts on my health. Six and
      12 months later, we measured the presence of troublesome neck pain (grades II-IV)
      using the Chronic Pain Questionnaire. Multivariable Cox regression was used to
      estimate the association between cardiovascular disorders and the troublesome
      neck pain while controlling for confounders. RESULTS: The follow-up rate was
      73.8% (680/922) at 6 months and 62.7% (578/922) at 1 year. No association was
      found between self-reported cardiovascular disorders that had no or mild impact
      on health and the onset of troublesome neck pain. We found a crude association
      between self-reported cardiovascular disorders that moderately or severely
      impacted health and the onset of troublesome neck pain (crude hazard rate ratio,
      4.3; 95% confidence interval, 1.8-10.0). The association was positively
      confounded by age, sex, and education (adjusted hazard rate ratio, 5.9; 95%
      confidence interval, 2.3-14.9). CONCLUSIONS: Our analysis suggests that self
      reported cardiovascular disorders that moderately or severely impact one's health
      are a risk factor for developing troublesome neck pain.

PMID- 22364916
TI  - Too close for comfort: screening strategy to detect methicillin-resistant
      Staphylococcus aureus conversion in exposed roommates.
AB  - All 899 roommates exposed to methicillin-resistant Staphylococcus aureus (MRSA)
      index cases were studied over 57 months. MRSA detection is better at
      approximately 3 days (50%-55%) or 7 days (56%) after contact has been broken than
      day 0 (30%). Polymerase chain reaction testing at day 3 performs similarly to
      culture at day 7. Nasal/rectal screening provides superior detection than nasal
      alone. Those exposed >48 hours are at significantly greater risk of colonization.

PMID- 22364917
TI  - Long-term survival curve of methicillin-resistant Staphylococcus aureus on
      clinical contact surfaces in natural-like conditions.
AB  - We investigated methicillin-resistant Staphylococcus aureus (MRSA) survival on a
      noncritical environmental surface in real-life conditions (dental chair located
      in a box of a Dentistry Department, subjected to microclimate variations and
      presence of people) and with a plausible baseline inoculum (5-log colony-forming
      units) in contrast to survival that has been frequently tested in laboratory
      conditions and/or using high baseline levels. We tested 5 freshly isolated
      sporadic strains and observed a drastic MRSA fall (>90%) 15 minutes after
      exposure to the environment. After 4 months, we detected MRSA at very low levels
      in 9 out of 25 tests. The MRSA survival curve showed that the velocity of log
      count decrease, highest soon after exposure, tended to decrease progressively.
      Thus, whereas the risk for infection through shared surfaces is probably minimal,
      the risk for MRSA diffusion in the community is high.

PMID- 22364918
TI  - An evaluation of immediate-use steam sterilization practices in adult knee and
      hip arthroplasty procedures.
AB  - BACKGROUND: Immediate-use steam sterilization (IUSS) is a safe method to
      sterilize emergently contaminated instruments, but inappropriate use may lead to
      an increased risk for surgical site infection. This study aimed to identify risk
      factors, rationale, and variability in procedural adherence in cases of IUSS.
      METHODS: This retrospective, case-control study compared adult patients
      undergoing hip and knee arthroplasty in which IUSS was (n = 104) and was not (n =
      81) performed. RESULTS: Multivariate analysis revealed 4 predictive risk factors
      for IUSS: history of malignancy (odds ratio [OR], 3.2 [95% confidence interval
      (CI) 1.1-9.3]), obesity (OR, 2.3 [95% CI: 1.02-5.2]), procedure performed in
      operating room 13 (OR, 2.5 [95% CI: 1.2-5.4]), and Monday procedure (OR, 3.6 [95%
      CI: 1.4-9.1]). The only factor that protected against IUSS was performing the
      procedure in the morning (OR, 0.4 [95% CI: 0.2-0.96]). Only 9.5% of cases of IUSS
      involved an acceptable indication. Documented adherence to core practices was
      also variable. CONCLUSION: Several patient- and case-specific factors can help
      predict the incidence of IUSS. Furthermore, practices should be hardwired to
      ensure IUSS is utilized for the correct indication. Documentation must be
      improved to allow institutions to accurately track IUSS.

PMID- 22364919
TI  - Application of electrolyte analysis of pleural effusion to diagnosis of drowning.
AB  - We measured concentrations of sodium (Na), chloride (Cl), calcium (Ca), and
      magnesium (Mg) in pleural effusion from forensic autopsy cases to examine whether
      they were useful for a diagnosis of drowning. We analyzed a total of 51 cases (15
      seawater drowning, 10 freshwater drowning, and 26 non-drowning), and determined
      the following reference values. If the concentration of Na or Cl is under 65
      mEq/l, a diagnosis of freshwater drowning can be made. If the concentration of Na
      is higher than 175 mEq/l, or that of Cl is higher than 155 mEq/l, or that of Ca
      is higher than 16 mg/dl, or that of Mg is higher than 15 mg/dl, a diagnosis of
      seawater drowning can be made. We recommend that pleural effusion from the left
      and the right thoracic cavities should be collected and analyzed separately
      because large differences may be observed between each side in the case of
      drowning. If one side corresponds to the reference value for seawater or
      freshwater drowning and the other side does not, a diagnosis of drowning can
      still be made according to the obtained value.

PMID- 22364921
TI  - Thymic stromal lymphopoietin downregulates NME1 expression and promotes invasion
      in human trophoblasts via the activation of STAT3 signaling pathway.
AB  - Our previous study has demonstrated that TSLP induces the invasion of human
      trophoblasts and plays a role in embryo implantation. The present study is
      undertaken to explore the mechanism by which TSLP modulates trophoblast invasion.
      It was revealed that TSLP treatment significantly downregulated NME1 and TIMP1
      expression in both human trophoblasts and JEG-3 cells. The stimulatory effect of
      TSLP on trophoblast invasion was partially inhibited by either STAT3 inhibitor or
      STAT5 inhibitor. The downregulation of NME1 expression by TSLP was completely
      abrogated by STAT3 inhibitor. TIMP1 expression was attenuated by NME1 siRNA
      interference and enhanced by NME1 overexpression in JEG-3 cells. TSLP-stimulated
      increase in trophoblast invasion was partially attenuated by NME1 overexpression.
      Our data suggest that TSLP might downregulate NME1 expression via STAT3 signaling
      pathway, affecting TIMP1 expression in influencing trophoblast invasion. Our
      studies suggest that further studies on TSLP as a potential therapeutic for
      recurrent spontaneous abortion are warranted.

PMID- 22364922
TI  - RETRACTED: Corrigendum to "Improved haplotype assembly using Xor genotypes" [J.
      Theor. Biol. 298 (2012) 122-130].
AB  - This Corrigendum has been withdrawn at the request of the authors. 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- 22364920
TI  - Transmethylation in immunity and autoimmunity.
AB  - The activation of immune cells is mediated by a network of signaling proteins
      that can undergo post-translational modifications critical for their activity.
      Methylation of nucleic acids or proteins can have major effects on gene
      expression as well as protein repertoire diversity and function. Emerging data
      indicate that indeed many immunologic functions, particularly those of T cells,
      including thymic education, differentiation and effector function are highly
      dependent on methylation events. The critical role of methylation in immunocyte
      biology is further documented by evidence that autoimmune phenomena may be
      curtailed by methylation inhibitors. Additionally, epigenetic alterations
      imprinted by methylation can also exert effects on normal and abnormal immune
      responses. Further work in defining methylation effects in the immune system is
      likely to lead to a more detailed understanding of the immune system and may
      point to the development of novel therapeutic approaches.

PMID- 22364923
TI  - The Fukushima Nuclear Power Station incident and marine pollution.
AB  - Based on the facts relating to the radioactive wastewater discharged by the
      Fukushima Nuclear Power Station in Japan, this paper intends to explore the
      international legal obligations for Japan from three perspectives, namely, the
      immediate notification, the prevention of transboundary harm and the prevention
      of dumping. Furthermore, this article defines and compares two types of
      international legal liabilities, the traditional state responsibility and the
      responsibility for transboundary harm. Through comparison, the international
      legal liability of Japan is discussed. After detailed analysis, the conclusion is
      that Japan should be responsible for the obligation of immediate notification and
      since Japan unilaterally discharge the wastes without prior specific permits of
      other contracting countries, it should also be responsible for the violation of
      prevention of dumping. Since so far, no material injury has emerged and there
      would appear to be no culpability as regards the prevention of transboundary
      harm. Finally, this paper stresses the necessity to develop a worldwide agreement
      concerning the liability for transboundary harm and to establish an institutional
      framework for the enforcement of a state's obligations, and also the great
      significance of international cooperation between nations and organisations in
      relation to marine environmental protection.

PMID- 22364924
TI  - A marine secondary producer respires and feeds more in a high CO2 ocean.
AB  - Climate change mediates marine chemical and physical environments and therefore
      influences marine organisms. While increasing atmospheric CO(2) level and
      associated ocean acidification has been predicted to stimulate marine primary
      productivity and may affect community structure, the processes that impact food
      chain and biological CO(2) pump are less documented. We hypothesized that
      copepods, as the secondary marine producer, may respond to future changes in
      seawater carbonate chemistry associated with ocean acidification due to
      increasing atmospheric CO(2) concentration. Here, we show that the copepod,
      Centropages tenuiremis, was able to perceive the chemical changes in seawater
      induced under elevated CO(2) concentration (>1700 MUatm, pH<7.60) with avoidance
      strategy. The copepod's respiration increased at the elevated CO(2) (1000 MUatm),
      associated acidity (pH 7.83) and its feeding rates also increased
      correspondingly, except for the initial acclimating period, when it fed less. Our
      results imply that marine secondary producers increase their respiration and
      feeding rate in response to ocean acidification to balance the energy cost
      against increased acidity and CO(2) concentration.

PMID- 22364925
TI  - MRI analysis for rotation of total knee components.
AB  - PURPOSE: The aim of this study was to analyze rotation of total knee (TKA)
      implant components using magnetic resonance imaging (MRI) and to assess the
      reproducibility of results. It was hypothesized that rotation of both femoral and
      tibial implants would be reliably reproduced. METHODS: A retrospective analysis
      of 55 MRI studies in subjects with painful TKA implants was conducted. There were
      27 zirconium and 28 cobalt/chrome/molybdenum alloy (CoCrMo) femoral components in
      the group. The rotation angle of femoral and tibial components was measured and
      determined. Statistical analysis included tests for reliability, variance between
      implant groups, standard deviations and confidence intervals. RESULTS: There was
      a sufficient inter- and intra-observer reliability determined for rotation in all
      implants. The inter-observer reliability was notably higher in the zirconium
      femur group with significant less variance and lower standard deviations than the
      CoCrMo femoral component comparison group. Standard deviations for femoral
      rotational analysis were within a clinically acceptable range. The standard
      deviations were considerably higher in the tibial component rotational analysis.
      CONCLUSION: MRI analysis of the rotation of femoral implants after TKA allows
      good reproducibility, especially with review of zirconium implants. There is less
      reproducibility for tibial components related to the applied geometric method to
      quantify rotation and not to the MRI technique.

PMID- 22364926
TI  - Anthropometric predictors of geometric indices of hip bone strength in a group of
      Lebanese postmenopausal women.
AB  - The effects of anthropometric characteristics on hip bone strength in
      postmenopausal women are not completely elucidated. The aim of this study was to
      investigate the influence of anthropometric characteristics on geometric indices
      of hip bone strength using the hip structure analysis (HSA) program in a group of
      Lebanese postmenopausal women. This study included 109 postmenopausal women (aged
      64--84yr). Age and years since menopause were recorded. Body composition and bone
      mineral density were assessed by dual-energy X-ray absorptiometry (DXA). To
      evaluate hip bone strength, DXA scans were analyzed at the femoral neck (FN), the
      intertrochanteric (IT), and the femoral shaft (FS) by the HSA program. Cross
      sectional area (CSA), an index of axial compression strength, section modulus
      (Z), an index of bending strength, and buckling ratio (BR), an estimate of
      cortical stability in buckling, were measured from bone mass profiles. Using
      univariate analysis, weight, height, body mass index (BMI), lean mass, and fat
      mass were positively correlated to CSA and Z of the FN, IT, and FS. Weight, BMI,
      fat mass, and fat mass percentage were negatively correlated to BR of the FN, IT,
      and FS. Multiple linear regression analysis showed that lean mass was a stronger
      determinant of FN CSA, FN Z, IT Z, and FS Z than fat mass, whereas fat mass was a
      stronger determinant of IT CSA, FS CSA, IT BR, and FS BR than lean mass. This
      study suggests that, in postmenopausal women, fat mass is a strong predictor of
      hip axial compression strength and cortical stability in buckling, and lean mass
      is a strong predictor of hip bending strength.

PMID- 22364927
TI  - [Experience with bosentan in a female patient with systemic lupus erythematosus
      and livedo racemosa].

PMID- 22364929
TI  - Biological sex and menstrual cycle phase modulation of cortisol levels and
      psychiatric symptoms in a non-clinical sample of young adults.
AB  - Prior research examined the complex, bidirectional interplay of the hypothalamic
      pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal axes and their roles
      in (clinical) cognitive/behavioral functions. Less well understood are
      contemporaneous relationships in non-clinical samples. This pilot study explored
      cortisol in relation to psychiatric symptoms/personality as a function of self
      reported menstrual cycle phase and sex differences in a non-clinical, young adult
      sample. Consistent with literature and hypotheses, cortisol levels were lowest
      during early-follicular, intermediary during late-follicular, and highest during
      mid-luteal phases (not significant), and greater among males than early
      follicular females. An acute stressor uniformly affected cortisol across phases
      and sex, though magnitude and time course differed. Psychiatric symptoms were
      greater among early-follicular/late-follicular females versus males, and early
      follicular and/or late-follicular versus mid-luteal. Contrary to hypotheses,
      positive psychotic-like symptoms were greater among males than (mid-luteal)
      females. Cortisol inversely related to early-follicular symptoms, and directly
      related to late-follicular/mid-luteal symptoms. Results suggest menstrual cycle
      phase modulates non-clinical psychiatric symptomatology and HPA activity.
      Findings tentatively bolster a dimensional/continuum model of psychopathology
      with implications for understanding neurobiological underpinnings and
      risk/protective factors for mental/physical health conditions, particularly those
      marked by sex differences and neuroendocrine dysfunction
      (depression/schizophrenia/Alzheimer's/multiple sclerosis). We speculate a dose
      response cortisol effect on symptoms, modulated by endogenous gonadal hormones
      via gene expression.

PMID- 22364928
TI  - Does stress induce (para)sex? Implications for Candida albicans evolution.
AB  - Theory predicts that stress is a key factor in explaining the evolutionary role
      of sex in facultatively sexual organisms, including microorganisms. Organisms
      capable of reproducing both sexually and asexually are expected to mate more
      frequently when stressed, and such stress-induced mating is predicted to
      facilitate adaptation. Here, we propose that stress has an analogous effect on
      the parasexual cycle in Candida albicans, which involves alternation of
      generations between diploid and tetraploid cells. The parasexual cycle can
      generate high levels of diversity, including aneuploidy, yet it apparently occurs
      only rarely in nature. We review the evidence that stress facilitates four major
      steps in the parasexual cycle and suggest that parasex occurs much more
      frequently under stress conditions. This may explain both the evolutionary
      significance of parasex and its apparent rarity.

PMID- 22364930
TI  - Diagnostic classifications in depression and somatization should include
      biomarkers, such as disorders in the tryptophan catabolite (TRYCAT) pathway.
AB  - The tryptophan catabolite (TRYCAT) pathway is induced by indoleamine 2,3
      dioxygenase (IDO), which upon activation depletes plasma tryptophan (TRP) and
      increases the synthesis of TRYCATs. Both phenomena are associated with
      somatization and depression. The aims of this study are to examine whether
      disorders in the TRYCAT pathway are specific to depression or somatization and
      whether the diagnoses somatization, depression, and comorbid
      depression+somatization reflect qualitatively distinct clinical and biological
      categories. Plasma TRP, the kynurenine (KY)/TRP and KY/kynurenic acid (KA) ratios
      were measured in 36 patients with somatization, 35 depressed and 38
      depressed+somatization patients and 22 controls. Using pattern recognition
      methods, the diagnosis comorbid depression+somatization could not be validated,
      while there was an important overlap between depression and somatization, which
      form one continuum. Cluster analysis detected a) a control cluster; b) a cluster
      with lower tryptophan, and higher KY/TRP and KY/KA ratios and somatization
      scores; and c) a cluster with increased depression but lower KY/TRP values. The
      differences between both patient clusters were quantitative and not qualitative.
      Within the patient group, cluster analysis has generated a "pathway phenotype",
      i.e. aberrations in the TRYCAT pathway, which are associated with somatization
      rather than with depression.

PMID- 22364931
TI  - Using the Johns Hopkins Aggregated Diagnosis Groups (ADGs) to predict mortality
      in a population-based cohort of adults with schizophrenia in Ontario, Canada.
AB  - Administrative health care databases are increasingly used for health services
      and comparative effectiveness research. When comparing outcomes between different
      treatments, interventions and exposures, the ability to adjust for differences in
      the risk of the outcome occurring between treatment groups is important. There is
      a paucity of validated methods to ascertain comorbidities for risk-adjustment in
      ambulatory populations of subjects with schizophrenia using administrative health
      care databases. Our objective was to examine the ability of th?e Johns Hopkins'
      Aggregated Diagnosis Groups (ADGs) to predict 1-year mortality in a population
      based cohort of subjects with schizophrenia. We used a retrospective cohort
      constructed using population-based administrative data that consisted of all
      94,466 residents of Ontario, Canada between the ages of 20 and 100years who were
      alive on January 1, 2007 and who had been diagnosed with schizophrenia prior to
      this date. Subjects were randomly divided into derivation and validation samples.
      A logistic regression model consisting of age, sex, and indicator variables for
      14 of the 32 ADG categories had excellent discrimination: the c-statistic
      (equivalent to the area under the ROC curve) was 0.845 and 0.836 in the
      derivation and validation samples, respectively. Furthermore, the model
      demonstrated very good calibration.

PMID- 22364932
TI  - Replication of the five-dimensional structure of positive psychotic experiences
      in young adulthood.
AB  - Previous work has examined the structure of subclinical positive psychotic
      experiences. The current study, using confirmatory factor analysis in a general
      population sample of young adult females, replicated a five-dimensional model,
      which showed excellent model fit. The results suggest stability of the five
      dimensional model across adolescent and young adult life.

PMID- 22364933
TI  - Evaluation of the factor structure of symptoms in patients with schizophrenia.
AB  - Considering the widespread use of the Positive and Negative Syndrome Scale
      (PANSS) and its factors around the world in clinical trials, it is clearly
      necessary to perform a transcultural validation of the factor structure of the
      PANSS. The purpose of the present study was to examine the PANSS factor structure
      in a Korean sample of subjects with schizophrenia. A total of 150 outpatients
      were assessed using the PANSS and other clinical rating scales. Principal
      component analyses revealed five factors, i.e., negative,
      cognitive/disorganization, positive, excitement, and depression/anxiety
      dimensions, which accounted for 64.1% of the total variance. All five factors
      showed good internal consistency, suggesting that the reliability of the factors
      extracted was adequate. Significant correlations were found between the five
      components of the PANSS and the corresponding clinical rating scales. The results
      of the present study indicate that the five-factor model best fit the data from
      our patients and that it was validated transculturally. The factor structures
      should be further validated using various neurobiological methods to ultimately
      help in clarifying the heterogeneity and pathogenesis of symptomatology in
      schizophrenia.

PMID- 22364934
TI  - Performance on the continuous performance test under parametric increase of
      working memory load in schizophrenia.
AB  - We asked 24 schizophrenia patients and 24 healthy comparison subjects to complete
      a parametric working memory version of the continuous performance test. Patients
      exhibited a relatively rapid performance decline with increasing working memory
      demands. We suggest an interaction between sustained attention and working memory
      abnormalities in schizophrenia.

PMID- 22364935
TI  - Dead bodies for the anatomical institute in the Third Reich: An investigation at
      the University of Jena.
AB  - During the period of 2004-2005, a group of anatomists and historians investigated
      the origin of dead bodies received by the anatomical institute of the University
      of Jena in the Third Reich. Between 1933 and 1945, the institute received the
      bodies of 203 executed persons, most of whom had been sentenced to death for
      relatively minor offenses or opposition to National Socialist (NS) regulations.
      Moreover, the institute received about 200 bodies of possible "euthanasia"
      victims from nearby nursing homes and mental institutions, and several dozen dead
      bodies of forced laborers from Eastern Europe. Many of these persons must be
      considered victims of NS injustice. One of the central questions of the
      investigation was whether any remains of NS victims were still present in the
      anatomical collections of the institute. At their own initiative, members of the
      anatomical institute initiated the investigation after a change of leadership at
      the institute. The investigation was characterized by (1) a scholarly approach
      thanks to the participation of expert historians, (2) transparency, including
      early and full information of the press, (3) documentation and publication of the
      results at the national and international level, (4) appropriate consequences for
      the anatomical collections, and (5) commemoration of the victims. This and other
      recent investigations demonstrate that a new generation of German anatomists has
      begun to uncover the role of their institutes during the Third Reich, finally
      overcoming the phase of silence in postwar German anatomy.

PMID- 22364936
TI  - Origin and immunophenotype of aberrant IEL in RCDII patients.
AB  - OBJECTIVES: Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of
      refractory coeliac disease type II RCDII and considered a premalignant cell
      population from which aggressive enteropathy-associated T cell lymphoma (EATL)
      can evolve. The aim of this study was to gain further insight in the origin and
      characteristics of aberrant IELs by analysing T-cell receptor (TCR)
      rearrangements, and by immunophenotypic analysis of aberrant IELs. DESIGN:
      Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed
      for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs
      isolated from biopsies derived from RCDII patients were phenotypically analysed.
      RESULTS: Aberrant IELs showed an upregulated expression of granzyme B and
      decreased expression of PCNA. TCR rearrangements in the aberrant IEL population
      in biopsies of RCDII patients were heterogenic, which is most likely due to a
      variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR
      rearrangement pattern. CONCLUSION: Aberrant IELs originate from deranged immature
      T lymphocytes and display clear differentiation to a cytotoxic phenotype.
      Aberrant IELs displayed different stages of maturity between RCDII patients, of
      which only the patients harbouring the most mature aberrant IEL population
      developed an EATL.

PMID- 22364938
TI  - 'Venous insufficiency' is not the cause of multiple sclerosis (MS) (but it could
      be a risk factor for MS and for different brain disorders).

PMID- 22364939
TI  - Chronic cerebrospinal venous insufficiency in multiple sclerosis: a historical
      perspective.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) is a term used to describe
      impaired venous drainage from the central nervous system (CNS) caused by
      abnormalities in anatomy and flow affecting the extracranial veins. Recently, it
      has been proposed that CCSVI may contribute to the pathogenesis of multiple
      sclerosis (MS). It is hypothesized that venous obstruction results in abnormal
      flow that promotes inflammation at the blood-brain barrier and that this triggers
      a process marked by a disturbance of homeostasis within the CNS that leads to
      demyelination and neurodegeneration. The venous abnormalities of CCSVI are often
      diagnosed by ultrasound or magnetic resonance venography, however the prevalence
      of CCSVI detailed in groups of MS patients and patients without MS varies widely
      in published reports. Increased standardization of diagnostic studies to evaluate
      both anatomical and physiological findings associated with CCSVI is needed. The
      purpose of this article is to provide a background to understand the development
      of the theory of CCSVI and to frame the relevant issues regarding its diagnosis
      and relationship to the pathogenesis of MS.

PMID- 22364940
TI  - Prevalence of extracranial venous abnormalities: results from a sample of 586
      multiple sclerosis patients.
AB  - The aim of this study was to assess the prevalence of chronic cerebrospinal
      venous insufficiency in an unselected cohort of multiple sclerosis (MS) patients.
      A total of 586 patients with clinically defined MS underwent catheter venography
      of the internal jugular veins, brachiocephalic veins and azygos vein. The
      following findings were regarded as pathologic: no outflow, slowed outflow,
      reversal of flow direction, prestenotic dilation accompanied by impaired outflow,
      outflow through collaterals, intraluminal structures obstructing the vein,
      hypoplasia, agenesia or significant narrowing of the vein. Venous abnormalities
      were found in 563 patients (96.1%). Lesions in one vein were found in 43.5%, in
      two veins in 49.5%, and in three veins in 3.1% of patients. Venous pathologies in
      the right internal jugular vein were found in 64.0% of patients, in the left
      internal jugular vein in 81.7%, in the left brachiocephalic vein in 1.0%, and in
      the azygos vein in 4.9%. Venous pathologies were found to be highly associated
      with MS, yet the clinical relevance of this phenomenon remains to be established.

PMID- 22364941
TI  - Sensitivity and specificity for screening of chronic cerebrospinal venous
      insufficiency using a multimodal non-invasive imaging approach in patients with
      multiple sclerosis.
AB  - The aim of this study was to investigate whether a combination of Doppler
      sonography (DS) and magnetic resonance venography (MRV) on 3T MRI increases
      specificity for detection of chronic cerebrospinal venous insufficiency (CCSVI)
      in 171 (113 relapsing-remitting, 47 secondary-progressive, 11 primary
      progressive) patients with multiple sclerosis (MS) and 79 age- and sex matched
      healthy controls (HCs). One hundred ten (64.3%) MS patients and 30 (38%) HCs
      presented >=2 venous hemodynamic CCSVI criteria (p<.0001). Both DS and MRV showed
      relatively high specificity but lower sensitivity for determining a CCSVI
      diagnosis in patients with MS vs HCs and between MS subgroups. In MS patients
      this diagnostic specificity increased to over 90% by combining internal jugular
      vein and vertebral vein abnormal DS and MRV findings, reflux in deep cerebral
      veins and MRV findings of >1 collateral veins. This study suggests that a
      multimodal non-invasive approach (DS and MRV) increases the specificity for a
      diagnosis of CCSVI in patients with MS.

PMID- 22364942
TI  - Cerebrospinal fluid flow dynamics in patients with multiple sclerosis: a phase
      contrast magnetic resonance study.
AB  - Cerebrospinal fluid (CSF) flow dynamics, which supposedly have a strong
      relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be
      expected to be affected in multiple sclerosis (MS) patients. In this study, CSF
      flow at the level of the cerebral aqueduct was evaluated quantitatively by phase
      contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow
      dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy
      controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and
      craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS
      patients compared with the controls. These findings may support the venous
      occlusion theory, but may also be explained by atrophy-dependent ventricular
      dilatation independent of the venous theory in MS patients.

PMID- 22364943
TI  - Cerebrovascular reactivity during the Valsalva maneuver in migraine, tension-type
      headache and medication overuse headache.
AB  - The aim of this study was to investigate, by means of transcranial Doppler
      ultrasound (TCD), cerebrovascular reactivity during the Valsalva maneuver (VM)
      during the headache-free interval in patients with migraine (M), migraine plus
      tension-type headache (M+TTH), and migraine plus medication overuse headache
      (M+MOH). A total of 114 patients (n=60 M, n=38 M+TTH, n=16 M+MOH) and n=60
      controls were investigated; diagnoses were made according to the International
      Headache Society criteria. All subjects underwent TCD monitoring and,
      simultaneously, non-invasive assessment of arterial blood pressure and end-tidal
      CO2. Two indices were determined: the cerebrovascular Valsalva ratio (CVR) was
      calculated as the maximum end-diastolic flow velocity acceleration during the
      late straining phase of the VM [cm/s2] and the centroperipheral Valsalva ratio
      (CPVR) was defined as the quotient of CVR to the concomitant arterial blood
      pressure acceleration [cm/mmHg x s]. The dynamic cerebrovascular autoregulatory
      response to the VM, measured as CVR, was increased in patients with M and M+TTH
      compared to age-matched healthy subjects. By contrast, CPVR (i.e. the quotient of
      the cerebrovascular to the peripheral autonomic response), was increased in M
      patients compared to healthy subjects and all other headache conditions tested.
      Cerebrovascular autoregulatory response during the VM was increased in M patients
      compared to age-matched normal healthy subjects, indicating a disturbed autonomic
      control of cerebral vasoreactivity. The CPVR seems to be a sensitive parameter
      for distinguishing between M patients and M+TTH or M+MOH patients.

PMID- 22364944
TI  - Screening for chronic cerebrospinal venous insufficiency (CCSVI) using
      ultrasound: recommendations for a protocol.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by
      stenoses or obstructions of the internal jugular and/or azygos veins with
      disturbed flow and formation of collateral venous channels. Ultrasound and
      venographic studies of the internal jugular and azygos venous systems in patients
      with multiple sclerosis (MS) have demonstrated a high prevalence of CCSVI (mean
      71%, range 0-100%; n=1336) associated with activation of collaterals. By
      contrast, ultrasound and venographic examinations of normal controls and patients
      without MS have demonstrated a much lower prevalence (mean 7.1%, range 0-22%;
      n=505). Ultrasound in the form of duplex scanning uses a combination of
      physiological measurements as well as anatomical imaging and has been used for
      the detection of CCSVI by different centers with variable results. A high
      prevalence of obstructive lesions, ranging from 62% to 100%, has been found by
      some teams in patients with MS compared with a low prevalence (0-25%) in
      controls. However, others have reported absence of these lesions or a lower
      prevalence (16-52%). This variability could be the result of differences in
      technique, training, experience or criteria used. In order to ensure a high
      reproducibility of duplex scanning with comparable accuracy between centers a
      detailed protocol with standard methodology and criteria is needed. Also,
      standardization of the method of reporting of duplex measurements and other
      findings will facilitate validation of the proposed criteria by different
      centers. The aim of this document is to produce recommendations for such a
      protocol and indicate what future research is needed in order to address areas of
      uncertainty.

PMID- 22364945
TI  - Smoking, nicotine and dementia.

PMID- 22364947
TI  - Adventitious agents, new technology, and risk assessment, 19-20 May 2011,
      Baltimore, MD.
AB  - In May 2011, the International Alliance for Biological Standardization, with the
      cooperation of WHO, FDA, and NIAID, organized a conference on adventitious agents
      that might be found in biological products using new technology
      (http://www.iabs.org/index.php/past-conference-reports/116-baltimore-2011
      slides). The implications of such findings on risk assessment also were
      considered. Topics that were addressed included: a) current routine testing--what
      are we doing now?; b) recent advances in testing--what tests are being
      explored/applied?; c) examples of finding agents with "new" techniques; and d)
      risk assessment, including recent WHO activities. A draft algorithm for risk
      assessment was discussed in terms of its applicability to a variety of potential
      new agents and the possibilities for improving it.

PMID- 22364946
TI  - Reduced oxidative tissue damage during endotoxemia in IRAK-1 deficient mice.
AB  - The generation of reactive oxygen species (ROS) triggered by bacterial endotoxin
      lipopolysaccharide (LPS) plays a key role during the pathogenesis of sepsis.
      Given the key role that the interleukin-1 receptor associated kinase-1 (IRAK-1)
      plays in LPS-mediated Toll-like-receptor 4 (TLR4) pathway, we herein tested
      whether deletion of IRAK-1 gene in mice may render protection from LPS-induced
      oxidative tissue damage. In this report, we studied the levels of oxidative
      stress in vital organs including liver, kidney, and brain from wild type (WT) and
      IRAK-1 deficient mice injected with a lethal dose of LPS (25mg/kg), a TLR4
      specific agonist. We demonstrated that LPS challenge induced marked elevation of
      lipid peroxidation and nitrite levels in the plasma and tissues of WT mice, as
      well as elevated pro-inflammatory mediators. In contrast, IRAK-1 deficient mice
      had significantly lower lipid peroxidation and nitrite levels, as well as lower
      levels of pro-inflammatory mediators. Mechanistically, LPS triggered higher
      levels of iNOS activity and elevated membrane translocation of p47(phox), a key
      component of NADPH oxidase in immune cell derived from WT mice compared to IRAK-1
      deficient mice. Additionally, tissues harvested from WT mice injected with LPS
      exhibited reduced activities of anti-oxidant enzymes including glutathione
      peroxidase (GPx), catalase, and superoxide dismutase (SOD). In contrast, LPS
      challenge failed to reduce the activities of GPx and SOD in IRAK-1 deficient
      tissues. As a consequence, LPS caused significantly pronounced damage to liver
      and kidney tissues in WT mice as compared to IRAK-1 deficient mice.

PMID- 22364948
TI  - Subconjunctival hemorrhage as a complication of intraoperative positioning for
      lumbar spinal surgery.

PMID- 22364949
TI  - Comment on "A set of rapid-response models for pollutant dispersion assessments
      in southern Spain coastal waters" by R. Perianez and F. Caravaca, Marine
      Pollution Bulletin 60 (2010) 1412-1422.

PMID- 22364950
TI  - Tolerance and accumulation of copper in the salt-marsh shrub Halimione
      portulacoides.
AB  - The present study evaluated the tolerance and accumulation potential in the salt
      marsh shrub Halimione portulacoides under moderate and high external Cu levels. A
      greenhouse experiment was conducted in order to investigate the effects of a
      range of external Cu concentrations (0 to 60 mmol l(-1)) on growth and
      photosynthetic performance by measuring gas exchange, chlorophyll fluorescence
      parameters and photosynthetic pigments. We also determined total copper,
      nitrogen, phosphorus and sulfur concentrations in the plant tissues. H.
      portulacoides survived with external Cu concentrations of up to 35 mmol Cu l(-1),
      although the excess of metal resulted in a biomass reduction of 48%. The effects
      of Cu on growth were linked to a drastic reduction in net photosynthesis.
      However, H. portulacoides tolerated Cu levels of up to 15 mmol Cu l(-1) without
      suffering adverse physiological effects. Our results indicate that this species
      could play an important role in the restoration of Cu-contaminated soils.

PMID- 22364951
TI  - Fine sediment and nutrient dynamics related to particle size and floc formation
      in a Burdekin River flood plume, Australia.
AB  - The extreme 2010-2011 wet season resulted in highly elevated Burdekin River
      discharge into the Great Barrier Reef lagoon for a period of 200 days, resulting
      in a large flood plume extending >50km offshore and >100km north during peak
      conditions. Export of suspended sediment was dominated by clay and fine silt
      fractions and most sediment initially settled within ~10km of the river mouth.
      Biologically-mediated flocculation of these particles enhanced deposition in the
      initial low salinity zone. Fine silt and clay particles and nutrients remaining
      in suspension, were carried as far as 100km northward from the mouth, binding
      with planktonic and transparent exopolymer particulate matter to form large floc
      aggregates (muddy marine snow). These aggregates, due to their sticky nature,
      likely pose a risk to benthic organisms e.g. coral and seagrass through
      smothering, and also by contributing to increased turbidity during wind-induced
      resuspension events.

PMID- 22364952
TI  - Synthesis and antidiabetic performance of beta-amino ketone containing nabumetone
      moiety.
AB  - We wish to report the further design and improved synthesis that resulted in two
      series of target molecules, TM-1 and TM-2, with remarkably simplified structures
      containing beta-amino ketone of discrete nabumetone moiety. These were obtained
      via a 'one-pot, two-step, three-component' protocol of Mannich reaction with
      yield up to 97%. A total of 28 out of 31 new compounds were characterized using
      (1)H NMR, (13)C NMR, ESI MS and HRMS techniques. Studies on their antidiabetic
      activities, screened in vitro at 10 MUg mL(-1) level, indicate that TM-2
      possesses peroxisome proliferator-activated receptor activation and alpha
      glucosidase inhibition activity significantly stronger than that of TM-1, and
      also that of the series B compounds that were previously synthesized by the
      group. Analysis of the structure-activity relationship points to the
      sulfanilamide unit as the most probable potent group of beta-amino ketone and, on
      the basis of which, a tangible strategy is presented for the development of new
      antidiabetic drugs.

PMID- 22364953
TI  - Identification of cytochrome P450 2D6 and 2C9 substrates and inhibitors by QSAR
      analysis.
AB  - This paper presents four new QSAR models for CYP2C9 and CYP2D6 substrate
      recognition and inhibitor identification based on human clinical data. The models
      were used to screen a large data set of environmental chemicals for CYP activity,
      and to analyze the frequency of CYP activity among these compounds. A large
      fraction of these chemicals were found to be CYP active, and thus potentially
      capable of affecting human physiology. 20% of the compounds within applicability
      domain of the models were predicted to be CYP2C9 substrates, and 17% to be
      inhibitors. The corresponding numbers for CYP2D6 were 9% and 21%. Where the
      majority of CYP2C9 active compounds were predicted to be both a substrate and an
      inhibitor at the same time, the CYP2D6 active compounds were primarily predicted
      to be only inhibitors. It was demonstrated that the models could identify
      compound classes with a high occurrence of specific CYP activity. An
      overrepresentation was seen for poly-aromatic hydrocarbons (group of
      procarcinogens) among CYP2C9 active and mutagenic compounds compared to CYP2C9
      inactive and mutagenic compounds. The mutagenicity was predicted with a QSAR
      model based on Ames in vitro test data.

PMID- 22364954
TI  - Single strand DNA catenane synthesis using the formation of G-quadruplex
      structure.
AB  - DNA is a good material for constructing nanostructures such as DNA origami. One
      of the challenges in this field is constructing a topologically complex
      structure. Here, we synthesized a DNA catenane through the formation of a G
      quadruplex structure. The formation of the DNA catenane was investigated by gel
      electrophoresis. Interestingly, the synthesized DNA catenane was destroyed by
      heat treatment. Because conventional methods to construct DNA catenane include
      enzymatic ligation or chemical reactions, DNA is cyclized by covalent bond
      connection and never destroyed by heat treatment. To our knowledge, this is the
      first report of the synthesis of DNA catenane without using covalent bonds. Our
      novel way of synthesizing DNA catenane may be of use in easily recoverable DNA
      topological labeling.

PMID- 22364956
TI  - [HIV infection and chronic inflammation: is the bacterial translocation the
      underlying cause?].
AB  - Currently, non-AIDS comorbidities (cardiovascular disease, non-AIDS-related
      cancers, liver disease, osteoporosis, etc.) have become an important cause of
      morbimortality in patients with human immunodeficiency virus type 1 (HIV-1)
      infection. The elevation of plasma markers of inflammation has been associated
      with the development of cardiovascular disease and death from all causes.
      Therefore, there is great interest in elucidating the underlying causes
      responsible for this persistent inflammatory status. The intestinal barrier
      disruption associated with HIV-1 infection may favor the passage of gut microbial
      products into the blood, resulting in immune stimulation. In this article we
      review the pathogenesis of bacterial translocation and its relevance to HIV-1
      infection.

PMID- 22364957
TI  - Arrhythmias (IV). Clinical approach to atrial tachycardia and atrial flutter from
      an understanding of the mechanisms. Electrophysiology based on anatomy.
AB  - In 2009, 2343 catheter ablation procedures were performed in Spain for focal
      atrial tachycardia or atrial flutter (typical and atypical), with a yearly growth
      rate of 8%, indicating the clinical importance of these arrhythmias. The classic
      categorization of atrial tachycardia and atrial flutter based on rate and
      morphological criteria has become almost irrelevant at a time when clinical
      electrophysiology may lead to curative intervention based on a definition of the
      mechanism, making it necessary to bring laboratory experience closer to clinical
      practice. In this review we outline our present understanding of atrial
      tachycardia mechanisms, both focal and macroreentrant, and attempt to establish
      the conceptual links with classic concepts that may help the clinician to make a
      differential diagnosis and establish therapeutic indications, including that of
      an electrophysiologic study. Some of the concepts may seem complex, but we
      thought it important to provide an overview of the electrophysiological methods
      that may eventually lead to the description of the anatomic bases of the
      arrhythmias; currently, these are easier to understand thanks to the virtual
      anatomic casts built using computerized navigation systems.

PMID- 22364955
TI  - Anaerobic power and muscle strength in human immunodeficiency virus-positive
      preadolescents.
AB  - OBJECTIVE: To determine the anaerobic power and muscle strength of preadolescents
      with human immunodeficiency virus (HIV). DESIGN: Cross-sectional design. SETTING:
      Human performance laboratory at the University District Hospital at the Puerto
      Rico Medical Center. PARTICIPANTS: Fifteen preadolescents (8 girls and 7 boys)
      with a classification of HIV A and B attending an investigational treatment
      program at the University Pediatric Hospital. Fifteen seronegative control
      subjects matched by age and gender also were included. MAIN OUTCOME MEASURES: The
      power of the lower extremities was measured with use of the Wingate Anaerobic
      Power Test on a MONARK cycle ergometer (mean power in watts). Local muscle
      strength of the dominant knee extensors (peak torque/body weight * 100) was
      tested with an isokinetic dynamometer set at 60 deg/s. Statistical analysis was
      performed with the Wilcoxon signed-rank test, and statistical significance was
      accepted at an alpha level of <.05. RESULTS: No significant differences between
      the control group and study group were detected on muscle strength testing. The
      study group presented a lower anaerobic power (mean power) compared with control
      subjects (P = .04). CONCLUSIONS: This exploratory study suggests that HIV
      infected preadolescents present lower anaerobic power compared with uninfected
      control subjects. Our findings of impaired anaerobic capacity can have clinical
      implications in this population because most of the activities of daily living,
      such as play, leisure, and sport activities, are short term and high intensity
      (anaerobic) in nature.

PMID- 22364958
TI  - Application of odor identification test in Parkinson's disease in China: a
      matched case-control study.
AB  - As one of the most common non-motor symptoms in Parkinson's disease (PD),
      hyposmia is of great importance in establishing the early diagnosis of PD. To
      date, there are still no studies on the application of the 16-item odor
      identification test from Sniffin' Sticks (SS-16) in Chinese patients with PD. The
      aim of this study was to investigate the validity of SS-16 in Chinese PD patients
      (n=110) compared with age and gender matched controls (n=110), and to explore the
      associated factors with olfactory function in PD patients. The 16 odors in the
      original odor identification test were retained but some alternative descriptions
      were developed before applications. Mean identification scores in patients were
      significantly lower than in controls (7.3 +/- 2.8 VS. 11.6 +/- 2.0 P<0.01), with
      66.4% of patients had an impairment of odor identification as evaluated by 95%
      confidential interval of the identification score of the control group. Receiver
      operating characteristic curves revealed 86% sensitivity and 81% specificity in
      separating PD and healthy controls with a cut-off value of 9.5. Multiple linear
      regression analysis revealed that autonomic dysfunction was a significant
      influential factor of odor identification scores in patients with PD. In
      conclusion, SS-16 provides a valid instrument for olfactory assessment in Chinese
      PD patients, and hyposmia may correlate with autonomic dysfunction in patients
      with PD.

PMID- 22364959
TI  - Transcriptional analysis of major chaperone genes in salt-tolerant and salt
      sensitive mesorhizobia.
AB  - Salinity is an important abiotic stress that limits rhizobia-legume symbiosis,
      affecting plant growth, thus reducing crop productivity. Our aims were to
      evaluate the tolerance to salinity of native chickpea rhizobia as well as to
      investigate the expression of chaperone genes groEL, dnaKJ and clpB in both
      tolerant and sensitive isolates. One hundred and six native chickpea mesorhizobia
      were screened for salinity tolerance by measuring their growth with 1.5% and 3%
      NaCl. Most isolates were salt-sensitive, showing a growth below 20% compared to
      control. An association between salt tolerance and province of origin of the
      isolates was found. The transcriptional analysis by northern hybridization of
      chaperone genes was performed using tolerant and sensitive isolates belonging to
      different Mesorhizobium species. Upon salt shock, most isolates revealed a slight
      increase in the expression of the dnaK gene, whereas the groESL and clpB
      expression was unchanged or slightly repressed. No clear relationship was found
      between the chaperone genes induction and the level of salt tolerance of the
      isolates. This is the first report on transcriptional analysis of the major
      chaperones genes in chickpea mesorhizobia under salinity, which may contribute to
      a better understanding of the mechanisms that influence rhizobia salt tolerance.

PMID- 22364960
TI  - Janus kinase (JAK) 2 V617F mutation as the cause of primary thrombocythemia in
      acromegaly with severe visceromegaly and divergence between growth hormone and
      insulin-like growth factor-1 concentrations during the follow-up: causal or
      casual association?
AB  - OBJECTIVE: An increased prevalence of hematological abnormalities is reported in
      acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2
      mutation in acromegalic patients have been described. DESIGN: We report the
      complex clinical presentation of the unique case, never described, of acromegaly
      due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation.
      RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2
      V617F mutation, severe visceromegaly and a peculiar clinical course of the
      disease characterized by discrepant values of GH and IGF-1 during somatostatin
      analog (SA) treatment despite a significant reduction in pituitary adenoma size
      and therapeutic resistance both to SA and pegvisomant. CONCLUSIONS: The presence
      of JAK2 V617F mutation is a cause of primary thrombocythemia and myelofibrosis in
      acromegaly. In this patient, a peculiar clinical course of acromegaly was
      observed, with the difficulty in controlling the disease. More data, on a larger
      cohort of patients, could clarify whether JAK2 V617F mutation has a serious
      impact on the clinical features and course of acromegaly.

PMID- 22364961
TI  - Estimating postprandial glucose fluxes using hierarchical Bayes modelling.
AB  - A new stochastic computational method was developed to estimate the endogenous
      glucose production, the meal-related glucose appearance rate (R(a meal)), and the
      glucose disposal (R(d)) during the meal tolerance test. A prior probability
      distribution was adopted which assumes smooth glucose fluxes with individualized
      smoothness level within the context of a Bayes hierarchical model. The new method
      was contrasted with the maximum likelihood method using data collected in 18
      subjects with type 2 diabetes who ingested a mixed meal containing [U
      13C]glucose. Primed [6,6-2H2]glucose was infused in a manner that mimicked the
      expected endogenous glucose production. The mean endogenous glucose production,
      R(a meal), and R(d) calculated by the new method and maximum likelihood method
      were nearly identical. However, the maximum likelihood gave constant,
      nonphysiological postprandial endogenous glucose production in two subjects
      whilst the new method gave plausible estimates of endogenous glucose production
      in all subjects. Additionally, the two methods were compared using a simulated
      triple-tracer experiment in 12 virtual subjects. The accuracy of the estimates of
      the endogenous glucose production and R(a meal) profiles was similar [root mean
      square error (RMSE) 1.0+/-0.3 vs. 1.4+/-0.7 MUmol/kg/min for EGP and 2.6+/-1.0
      vs. 2.9+/-0.9 MUmol/kg/min for R(a meal); new method vs. maximum likelihood
      method; P=NS, paired t-test]. The accuracy of R(d) estimates was significantly
      increased by the new method (RMSE 5.3+/-1.9 vs. 4.2+/-1.3; new method vs. ML
      method; P<0.01, paired t-test). We conclude that the new method increases
      plausibility of the endogenous glucose production and improves accuracy of
      glucose disposal compared to the maximum likelihood method.

PMID- 22364962
TI  - Group art therapy as an adjunctive treatment for people with schizophrenia: a
      randomised controlled trial (MATISSE).
AB  - OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of
      referral to group art therapy plus standard care, compared with referral to an
      activity group plus standard care and standard care alone, among people with
      schizophrenia. DESIGN: A three-arm, parallel group, single-blind, pragmatic,
      randomised controlled trial. Participants were randomised via an independent and
      remote telephone randomisation service using permuted blocks, stratified by study
      centre. SETTING: Study participants were recruited from secondary care mental
      health and social services in four UK centres. PARTICIPANTS: Potential
      participants were aged 18 years or over, had a clinical diagnosis of
      schizophrenia, confirmed by an examination of case notes, and provided written
      informed consent. We excluded those who were unable to speak sufficient English
      to complete the baseline assessment, those with severe cognitive impairment and
      those already receiving arts therapy. INTERVENTIONS: Group art therapy was
      delivered by registered art therapists according to nationally agreed standards.
      Groups had up to eight members, lasted for 90 minutes and ran for 12 months.
      Members were given access to a range of art materials and encouraged to use these
      to express themselves freely. Activity groups were designed to control for the
      non-specific effects of group art therapy. Group facilitators offered various
      activities and encouraged participants to collectively select those they wanted
      to pursue. Standard care involved follow-up from secondary care mental health
      services and the option of referral to other services, except arts therapies, as
      required. MAIN OUTCOME MEASURES: Our co-primary outcomes were global functioning
      (measured using the Global Assessment of Functioning Scale - GAF) and mental
      health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS)
      at 24 months. The main secondary outcomes were level of group attendance, social
      functioning, well-being, health-related quality of life, service utilisation and
      other costs measured 12 and 24 months after randomisation. RESULTS: Four hundred
      and seventeen people were recruited, of whom 355 (85%) were followed up at 2
      years. Eighty-six (61%) of those randomised to art therapy and 73 (52%) of those
      randomised to activity groups attended at least one group. No differences in
      primary outcomes were found between the three study arms. The adjusted mean
      difference between art therapy and standard care at 24 months was -0.9 [95%
      confidence interval (CI) -3.8 to 2.1] on the GAF Scale and 0.7 (95% CI -3.1 to
      4.6) on the PANSS Scale. Differences in secondary outcomes were not found, except
      that those referred to an activity group had fewer positive symptoms of
      schizophrenia at 24 months than those randomised to art therapy. Secondary
      analysis indicated that attendance at art therapy groups was not associated with
      improvements in global functioning or mental health. Although the total cost of
      the art therapy group was lower than the cost of the two comparison groups,
      referral to group art therapy did not appear to provide a cost-effective use of
      resources. CONCLUSIONS: Referring people with established schizophrenia to group
      art therapy as delivered in this randomised trial does not appear to improve
      global functioning or mental health of patients or provide a more cost-effective
      use of resources than standard care alone. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN 46150447. FUNDING: This project was funded by the NIHR Health
      Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 16, No. 8. See the HTA programme website for further
      project information.

PMID- 22364963
TI  - Use of the nitroblue tetrazolium reduction test for the evaluation of Domperidone
      effects on the neutrophilic function of healthy dogs.
AB  - The nitroblue tetrazolium reduction test (NBT) is an assay based on the
      activation percentage of neutrophils in peripheral blood, that has been proposed
      for the follow up of canine leishmaniosis owing to the narrow relationship
      between the molecules involved in the oxidative burst and the leishmanicidal
      activity of phagocytes. Domperidone is a drug used for the treatment of canine
      leishmaniosis having been claimed to stimulate the dogs' cell-mediated immune
      response. The aim of this study was to evaluate the degree and the lasting of
      phagocytic activation induced by a 30-day course treatment with Domperidone (0.5
      mg/kg/day) in healthy dogs, by using the NBT. A statistically significant
      increase in the percentages of activated phagocytes was observed in the treated
      group during treatment, thereafter remaining high for up to one month after the
      end of treatment. In contrast, untreated dogs maintained the baseline percentage
      of activated neutrophils all along the study. It is concluded that the NBT is a
      useful tool for the follow up of the stimulating effects of Domperidone on the
      neutrophilic response of healthy dogs and that these effects persist for up to
      one month after treatment with this molecule.

PMID- 22364964
TI  - Tuberculosis trends in the Kingdom of Saudi Arabia, 2005 to 2009.
AB  - PURPOSE: Policymakers should know the distribution and determinants of
      tuberculosis (TB) over time. This is especially true for the Kingdom of Saudi
      Arabia (KSA), a country at increased risk for TB transmission because of mass
      gatherings (e.g., Hajj) and a large number of immigrant workers. METHODS: Using
      national TB notification data reported from 13 provinces from 2005 through 2009,
      trends in annual TB incidence were calculated by nationality, age, and gender.
      RESULTS: Compared with Saudis, non-Saudis had a 2-fold greater TB incidence rate
      each year. In 2009 among all KSA provinces, Makkah had the greatest proportion of
      non-Saudis (38%), the greatest number of TB cases (1648), and the highest TB
      incidence rate (26 per 100,000). We observed significantly increasing yearly
      trends of TB incidence among Saudis in the Najran province (21.3%) and in Riyadh
      (8.5%). Conversely, we observed a significantly decreasing yearly trend among non
      Saudis in Baha (23.1%), Hail (17.4%), and the Eastern region (22.6%).
      CONCLUSIONS: Disparate KSA regional and longitudinal TB trends existed from 2005
      through 2009, by nationality. We recommend a review of all TB policies in KSA
      that addresses screening for latent TB infection and drug resistance.
      Additionally, we recommend a new TB public health education program.

PMID- 22364965
TI  - Invited commentary.

PMID- 22364966
TI  - Invited commentary.

PMID- 22364967
TI  - Thoracic or thoracoabdominal approaches to endovascular device removal and open
      aortic repair.
AB  - BACKGROUND: Endovascular aortic repair is becoming increasingly common and
      diverse in its application despite ongoing uncertainty about long-term
      durability. Recent reports detail late conversion to open surgical repair to
      treat disease progression and repair failure. We describe our experience with
      using thoracic or thoracoabdominal approaches to endovascular device removal and
      open aortic repair after previous endovascular procedures. METHODS: Thirty-five
      patients underwent open aortic repair through thoracotomy (n=7) or
      thoracoabdominal incision (n=28) 0.5 to 48 months after undergoing endovascular
      thoracic (n=27) or abdominal (n=8) aortic procedures. Indications for open repair
      included expanding aneurysm (n=23), device infection (n=8), fistula (n=5),
      pseudoaneurysm (n=2), aneurysm rupture (n=2), and restenosis (n=1). Endovascular
      devices were completely removed in 26 patients and partially removed in 9.
      Descending thoracic aortic repair was performed in 10 patients, thoracoabdominal
      aortic repair in 24, and juxtarenal abdominal aortic repair in 1. RESULTS: There
      were 2 in-hospital deaths (6%), both in patients who presented with endovascular
      device infection. There were 8 late deaths. Overall 1-year survival was 83%+/-7%.
      Among the patients who presented with infected devices, 3 experienced major late
      complications, including persistent infection, pseudoaneurysm, and recurrent
      fistula; 2 of these patients succumbed to late deaths. CONCLUSIONS: Open surgical
      repair after previous endovascular aortic procedures is successful in the
      majority of patients, particularly in those without device infections. Achieving
      definitive aortic repair in patients with infected endovascular devices is
      particularly challenging.

PMID- 22364968
TI  - Noninferiority of closely monitored mechanical valves to bioprostheses
      overshadowed by early mortality benefit in younger patients.
AB  - BACKGROUND: Confidence in bioprosthetic durability without anticoagulation has
      led to a contemporary trend of offering tissue valves to younger patients. Close
      monitoring of mechanical valve patients at lower international normalized ratio
      (INR) thresholds may reduce anticoagulation morbidity. We prospectively compared
      results of bioprostheses (BP) and a bileaflet mechanical prosthesis (MP)
      monitored at low INR thresholds. METHODS: Patients received an isolated
      Carpentier-Edwards bovine or Medtronic porcine BP or the On-X MP. INR targets
      were 2.0 for MP recipients undergoing aortic valve replacement and 2.5 for mitral
      valve replacement, using point-of-care home monitoring. Operations consecutively
      performed between September 2003 and August 2007 were propensity matched using
      logistic regression by preoperative covariates of age, sex, valve position, New
      York Heart Association class, ejection fraction, atrial fibrillation, and
      creatinine. RESULTS: Of 469 operations consecutively performed, 172 patients were
      matched for analysis. Mean age was 56.2+/-9.6 years (range, 24 to 72 years).
      Median follow-up was 4.0 years (total follow-up, 667.0 patient-years). No late
      bleeding events occurred. The thromboembolic complication rates per patient-year
      were 0.77% for MP and 0.78% for BP (p=0.67). There were 9 BP deaths vs 4 MP
      (2.35% vs 1.41%/patient-year; BP hazard ratio, 0.60; 95% confidence interval,
      0.13 to 2.15). Postoperative linearized mortality benefit of MP was observed as
      early as 5 years, reaching significance at 7.5 years (p=0.04). CONCLUSIONS:
      Patients aged 65 years or younger with MP and closely monitored anticoagulation
      display noninferiority to BP from bleeding and thromboembolic complications. MP
      valves begin to confer mortality benefit over BP as early as 7.5 years
      postoperatively. Because this predates the timeline of typical structural valve
      degeneration, equipoise is suggested when choosing a BP in a young patient with
      future expectations of valve-in-valve intervention.

PMID- 22364969
TI  - Invited commentary.

PMID- 22364970
TI  - Quality of life after early mitral valve repair using conventional and robotic
      approaches.
AB  - BACKGROUND: Early mitral valve (MV) repair of degenerative mitral regurgitation
      is associated with superior clinical outcomes compared with prosthetic
      replacement and restores normal life expectancy, even in those without symptoms.
      Although current guidelines recommend prompt referral for effective MV repair in
      those with severe mitral regurgitation, some are reluctant to pursue early
      correction due to the perception that short-term quality of life (QOL) may be
      adversely affected by the operation. METHODS: Between January 2008 and November
      2009, 202 patients underwent conventional transsternotomy or minimally invasive
      port-access robot-assisted MV repair, with or without patent foramen ovale
      closure or left Maze, and were mailed a postsurgical QOL survey. RESULTS:
      Unadjusted QOL scores for patients undergoing MV repair were excellent early
      after the operation using both approaches. Robotic repair was associated with
      slightly improved scores on the Duke Activity Status Index, the Short Form-12
      Item Health Survey Physical domain, and the Linear Analogue Self-Assessment
      frequency of chest pain and fatigue indices during the first postoperative year;
      however, differences between treatment groups became indistinguishable after 1
      year. Robotic repair patients returned to work slightly quicker (median, 33 vs 54
      days, p<0.001). CONCLUSIONS: Functional QOL outcomes within the first 2 years
      after early MV repair are excellent using open and robotic platforms. A robotic
      approach may be associated with slightly improved early QOL and return to
      employment-based activities. These results may have implications regarding future
      evolution of clinical guidelines and economic health care policy.

PMID- 22364971
TI  - Invited commentary.

PMID- 22364972
TI  - Surgical risk and outcome of repair versus replacement for late tricuspid
      regurgitation in redo operation.
AB  - BACKGROUND: Late tricuspid regurgitation after previous cardiac operation remains
      controversial in terms of when to repair and who will benefit. We reviewed our
      surgical experiences and stratified the risk factors for death and morbidity.
      METHODS: From September 2005 to September 2010, 77 consecutive patients (36 men
      [47%]) underwent redo open heart operations with the tricuspid valve (TV)
      procedure. Their mean age was 56+/-13 years (range, 27 to 83 years). TV repair
      was performed in 44 (57%) and TV replacement in 33 (43%): 23 received
      bioprostheses; 10 received mechanical prostheses. RESULTS: Fourteen (18%)
      patients died after the operation. Risk factors of hospital death by multivariate
      analysis were age (>65 years), preoperative renal insufficiency (creatinine>2
      mg/dL), and preoperative severe liver cirrhosis (Child classification C).
      Compared with the group that underwent TV repair, those who underwent TV
      replacement tended to have had previous TV operations (46% vs 9%; p<0.001) and
      preoperative Child class C liver cirrhosis (21% vs 2%; p=0.018). Although in
      hospital mortality was insignificant (24% vs 14%; p=0.232), postoperative
      morbidities of tracheotomy, gastrointestinal bleeding, and late death were higher
      in the replacement group. CONCLUSIONS: Patients who had previous TV operations
      and preoperative severe liver cirrhosis were more likely to undergo TV
      replacement in tricuspid reoperations. Compared with patients in the repair
      group, patients in the replacement group had higher morbidities and low late
      survival. Earlier intervention, before decompensated heart failure occurs, is
      warranted to improve the outcome.

PMID- 22364973
TI  - Melody valve-in-ring procedure for mitral valve replacement: feasibility in four
      annuloplasty types.
AB  - BACKGROUND: The recurrence of regurgitation after surgical mitral valve (MV)
      repair remains a significant clinical problem. Mitral annuloplasty rings are
      commonly used in MV repair procedures. The purpose of this study was to
      demonstrate the feasibility of transvenous valve-in-ring (VIR) implantation using
      the Melody valve (Medtronic, Minneapolis, MN), which is a valved-stent designed
      for percutaneous pulmonary valve replacement, and 4 distinct types of
      annuloplasty ring (AR) in an ovine model. METHODS: Ten sheep underwent surgical
      MV annuloplasty ring placement (n=10): CE-Physio, Edwards Lifesciences, Irvine,
      CA [n=5]; partial ring [n=3]; flexible ring [n=1]; and saddle ring [n=1]). All
      animals underwent cardiac catheterization, hemodynamic assessment, and Melody VIR
      implantation through a transfemoral venous, transatrial septal approach 1 week
      after surgery. Follow-up hemodynamic, angiographic, and echocardiographic data
      were recorded. RESULTS: Melody VIR implantation was technically successful in all
      but 1 animal. In this animal a 26-mm partial AR proved too large for secure
      anchoring of the Melody valve. In the remaining 9 animals, fluoroscopy showed the
      Melody devices securely positioned within the annuloplasty rings.
      Echocardiography revealed no perivalvular leak, and angiography revealed no left
      ventricular outflow tract obstruction, vigorous left ventricular function, and no
      aortic valve insufficiency. The median procedure time was 55.5 (range, 45 to 78)
      minutes. CONCLUSIONS: This study demonstrates the feasibility of a purely
      percutaneous approach to MV replacement in patients with preexisting annuloplasty
      rings, regardless of ring type. This approach may be of particular benefit to
      patients with failed repair of ischemic mitral regurgitation.

PMID- 22364974
TI  - Invited commentary.

PMID- 22364975
TI  - Invited commentary.

PMID- 22364976
TI  - Serial changes in renal function as a prognostic indicator in advanced heart
      failure patients with left ventricular assist system.
AB  - BACKGROUND: Left ventricular assist system (LVAS) implantation is an established
      treatment for patients with advanced heart failure. We investigated the clinical
      implication of serial changes in renal function after LVAS implantation. METHODS:
      This study included 110 patients who underwent pulsatile LVAS implantation
      intended as a bridge to transplantation and were alive more than 2 weeks after
      implantation. Data collection of demographic and hematologic values was performed
      1 day before (baseline) and 2 weeks after implantation. All patients were
      monitored for 2 years or until death. RESULTS: The 2-year postimplantation
      mortality rate was 31.8%. Multivariate Cox regression analysis showed the
      baseline estimated glomerular filtration rate (eGFR) was an independent predictor
      of death (hazard ratio, 0.90 for each 10 mL/min increase, p<0.05). The eGFR
      significantly increased at 2 weeks after LVAS implantation (70.5+/-37.8 to
      121.0+/-78.8 mL/min, p<0.01). Kaplan-Meier curves with log-rank tests showed
      significantly poorer event-free survival rates in the group with an inframedian
      value of change in eGFR at 2 weeks after implantation (DeltaeGFR; p=0.03) as well
      as in the group with the lowest tertile of eGFR at 2 weeks after implantation (2w
      eGFR; p<0.01). Multivariate Cox regression analysis showed that DeltaeGFR (hazard
      ratio, 0.89 for each 10 mL/min increase) and 2w-eGFR (hazard ratio, 0.92 for each
      10 mL/min increase) were independent predictors of death (p<0.01, respectively).
      CONCLUSIONS: Impaired renal function, and in particular, a poor response of eGFR
      to LVAS implantation, may have a strong association with worse outcome.

PMID- 22364977
TI  - Invited commentary.

PMID- 22364978
TI  - Invited commentary.

PMID- 22364979
TI  - Invited commentary.

PMID- 22364980
TI  - Invited commentary.

PMID- 22364981
TI  - Invited commentary.

PMID- 22364982
TI  - Similar outcomes after primary and secondary esophagocoloplasty for caustic
      injuries.
AB  - BACKGROUND: The main purpose of the study was to report a comparative experience
      with primary and secondary esophagocoloplasty for caustic injuries. Secondary
      esophagocoloplasty is the main rescue option after graft loss, but data in the
      literature are scarce. METHODS: The operative characteristics, postoperative
      course, and functional outcomes of 21 secondary and of 246 primary
      esophagocoloplasty operations performed for caustic injuries between 1987 and
      2006 were compared. Intraoperative events requiring significant changes in the
      planned operative strategy, such as graft ischemia or necrosis, were recorded.
      Statistical tests were performed in both cohorts to identify factors predictive
      of postoperative graft necrosis. Univariate analysis was performed to identify
      factors predictive of functional failure after secondary esophagocoloplasty.
      RESULTS: Operative mortality (5% vs 4%, p=0.56), morbidity (62% vs 59%, p=0.96),
      postoperative graft necrosis (14% vs 7%, p=0.16), and functional success (68% vs
      70%, p=0.79) rates of the secondary and primary esophagocoloplasty operations
      were similar. Intraoperative graft ischemia at the time of secondary
      esophagocoloplasty was significantly associated with the risk of postoperative
      graft necrosis (p=0.015) and functional failure (p=0.046). At the time of primary
      esophagocoloplasty, intraoperative necrosis of the colon was the only independent
      predictive factor of postoperative graft necrosis (p<0.0001). CONCLUSIONS:
      Secondary esophagocoloplasty is a safe and reliable salvage option after primary
      graft loss in patients with caustic injuries. Delayed esophagocoloplasty should
      be considered if intraoperative colon necrosis occurs at the time of primary
      reconstruction.

PMID- 22364983
TI  - Donor type impact on ischemia-reperfusion injury after lung transplantation.
AB  - BACKGROUND: Extended criteria donors, non-heart-beating donors (NHBD), and living
      donation are options to overcome the organ shortage for lung transplantation
      (LTx). However little is known about the impact of the donor lung on ischemia
      reperfusion injury (IRI), which often leads to high mortality rates. METHODS:
      Recipient pigs (N=32) were divided equally into 4 groups according to their donor
      status: (1) living donor=control group, (2) conventional heart-beating donor, (3)
      non-heart-beating donor according to Maastricht category I (NHBD-I), and (4)
      Maastricht category IV (NHBD-IV). After cold flush and 3 hours of hypothermic
      preservation, a single left LTx was performed. Thereafter only the transplanted
      left lung was ventilated and perfused to assess isolated left lung function at 1
      and 2 hours after LTx compared with before LTx. RESULTS: No significant
      differences were seen between the 4 groups regarding wet-to-dry weight ratio,
      mean airway pressure, or compliance. Arterial oxygenation and alveolar-arterial
      difference showed significant differences between the groups (p<0.05). Two-way
      analysis of variance (ANOVA) for the factors brain death and cardiac arrest found
      significantly increased alveolar-arterial differences for the brain-death group
      but not for the beating-heart donor group. CONCLUSIONS: The use of lungs from
      brain-death donors and NHBDs has different effects on the occurrence of symptoms
      of IRI after LTx. Further observations and therapeutic strategies are necessary
      to minimize IRI when grafts from NHBDs are used.

PMID- 22364984
TI  - Influence of age and IB status after resection of node-negative non-small cell
      lung cancer.
AB  - BACKGROUND: Anatomic segmentectomy has been proposed as a reasonable alternative
      to lobectomy in the management of small early-stage non-small cell lung cancers.
      We reviewed our outcomes with anatomic segmentectomy versus lobectomy for stages
      IA and IB non-small cell lung cancer stratified by age and stage. METHODS: We
      conducted a retrospective review of prospectively-collected data analyzing
      outcomes after anatomic segmentectomy (n=305) for stage IA (n=187) or IB (n=118)
      NSCLC from 1999 to 2010. Lobectomy was performed in 594 patients for stage IA
      (n=290) and IB (n=304) disease during the same period. Surgical approach was
      stratified by stage and by the following age groups: less than 70, 70 to 79, and
      80 or greater. Primary outcome variables included complications, mortality,
      recurrence patterns, and survival. Mean follow-up was 37 months. RESULTS:
      Segmentectomy was associated with reduced complications (43.6% vs 58.7%) and
      mortality (0% vs 7.8%) in patients greater than 80 years old, without a
      difference in recurrence rates. There was no difference in complications or
      mortality in the younger age groups. Freedom from recurrence was similar between
      segmentectomy and lobectomy for stage IA tumors across all age groups. A reduced
      recurrence-free survival was seen with segmentectomy for stage IB tumors,
      especially with visceral pleural invasion (median 22.7 vs 29.6 months), p=0.048).
      CONCLUSIONS: Segmentectomy appears to be a reasonable approach for early-stage
      NSCLC in patients 80 years of age or greater due to reduced morbidity and
      mortality with equivalent freedom from recurrence. Although equivalent survival
      was seen in all age groups for stage IA, these data further support the use of
      lobectomy for resection of stage IB tumors.

PMID- 22364985
TI  - A new morphologic classification of congenital tracheobronchial stenosis.
AB  - BACKGROUND: Congenital tracheal stenoses are rare and life-threatening anomalies,
      associated with considerable variation in both morphology and prognosis. They
      have been classified previously according to the length of the stenosis or the
      severity of the symptoms, but not according to bronchial involvement. METHODS:
      Data from patients who underwent slide tracheoplasty for long-segment (>50%)
      congenital tracheal stenosis were collected. We identified four different types
      of bronchial arborization (normal, n=52; tracheal right upper lobe bronchus,
      n=10; carina with "trifurcation," n=14; and unilateral bronchial and lung
      agenesis, n=8). Each type included congenital tracheal (above the carina) or
      tracheobronchial (extending below the carina) stenosis. RESULTS: Eighty-four
      children were enrolled in the study. Preoperative ventilation was necessary in 44
      patients (52.4%; 75% in patients with a single lung), and preoperative
      extracorporeal membrane oxygenation was needed in 10 patients (11.9%).
      Preoperative tracheostomy was present in 3 patients initially treated elsewhere
      (3.5%), and a left pulmonary artery sling was performed in 44% (37 of 84). The
      overall mortality was 13% (11 of 84), 7.9% in patients with tracheal stenosis and
      28.6% with tracheobronchial stenosis. No deaths occurred in patients with right
      upper lobe bronchus anatomy. Endoscopic procedures after slide tracheoplasty were
      required in 34 patients (40.4%). Stents were placed in 18 patients (21.4%), with
      a higher incidence in those with bronchial trifurcation (42.8%, 6 of 12).
      CONCLUSIONS: This classification appears useful for the morphologic
      characterization of congenital airway stenosis and could be the benchmark for
      future prospective studies on the outcome of these patients.

PMID- 22364986
TI  - Invited commentary.

PMID- 22364987
TI  - Initial pediatric cardiac experience with decellularized allograft patches.
AB  - PURPOSE: This study examines use patterns, early outcomes, and technical surgical
      adaptability of a newly approved decellularized allograft pulmonary artery patch
      for right ventricular outflow tract reconstructions in neonates and infants,
      including primary operations and reoperations. DESCRIPTION: The study includes
      the 44 consecutive initial patients in which 46 patches were used for
      cardiovascular reconstruction between September 2009 and September 2010. Recorded
      variables include sex, age at operation, adverse outcome end points (eg, death,
      stenosis, aneurysm), congenital diagnoses, postoperative complications, and
      number, type, and location of patches. EVALUATION: Patients were a mean age of
      290+/-343 days at operation, and 54.5% were boys. Three types of patch were used:
      58.7% thin, 21.7% thick, and 19.6% hemipulmonary. No device-related deaths or
      adverse events occurred. A biopsy specimen of one patch at elective reoperation
      demonstrated active recellularization, with no inflammation. CONCLUSIONS: These
      patches have a wide range of applicability. Handling and technical flexibility is
      excellent and superior to standard options. There appears to be potential for
      autologous revitalization of the tissue.

PMID- 22364988
TI  - Long-term durability of a St. Jude medical X-cell bioprosthesis.
AB  - An 82-year-old female had undergone aortic valve replacement with a 23-mm St.
      Jude Medical X-Cell porcine bioprosthesis (XCB), a glutaraldehyde-fixed valve
      subjected to a decellularization process. More than 13 years later, she required
      a repeated operation because of XCB structural failure. Pathologic examination of
      an unused XCB as control showed that many interstitial cells were still present
      in the porcine cusps. The XCB explant exhibited gross mineralization on
      radiograph, fairly well-preserved fibrosa, lack of interstitial and endothelial
      cells, scattered empty spaces with plasma insudation, and calcific deposits.
      Ultrastructural examination revealed calcium deposition on collagen fibers and
      cell debris. Partial cusp decellularization observed in an XCB was not effective
      in preventing mineralization and most likely should be associated with other
      antimineralization treatments as well as methods favoring cell repopulation in
      vitro or in vivo.

PMID- 22364989
TI  - Unusual cause of acute mitral regurgitation: idiopathic hypereosinophilic
      syndrome.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare multisystem condition
      characterized by dysregulated overproduction of eosinophils. Cardiac involvement
      in HES is characterized by necrosis from infiltration of eosinophils and thrombus
      formation and, in the late stage, by fibrosis and chronic valvular regurgitation.
      We report a very unusual presentation of idiopathic HES with acute mitral
      regurgitation due to papillary muscle rupture. The transesophageal echocardiogram
      was suggestive of a flail posterior leaflet and suspicious for endocarditis.
      Intraoperatively, papillary muscle rupture was seen and the patient underwent
      mitral valve replacement. The pathologic examination of the valve revealed
      eosinophilic infiltration of the papillary muscle. The patient was treated with
      steroids and responded well clinically.

PMID- 22364990
TI  - Implantation of the HeartWare HVAD in a child after a recent thromboembolic
      stroke.
AB  - We report the implantation of a HeartWare left ventricular assist device in a
      child. A 9-year-old girl presented in cardiogenic shock complicated by an embolic
      stroke. Catheter-based thrombolysis partially reversed the neurologic deficit,
      but worsening cardiac failure prompted consideration of mechanical circulatory
      support (MCS). Limited available pericardial space, anticoagulation requirements,
      and thromboembolic potential favored the use of the HeartWare left ventricular
      assist device (HeartWare International, Inc, Framingham, MA). After device
      implantation and intensive physical rehabilitation, the patient underwent
      successful cardiac transplantation after 60 days of support.

PMID- 22364991
TI  - Percutaneous ventricular assist device in hypertrophic obstructive cardiomyopathy
      with cardiogenic shock: bridge to myectomy.
AB  - We present the case of a 69-year-old woman with end-stage hypertrophic
      obstructive cardiomyopathy who developed cardiogenic shock. She underwent
      emergent placement of a percutaneous left ventricular assist device (TandemHeart)
      in the catheterization lab as a bridge support device until a septal myectomy
      could be performed as definitive treatment. This case suggests a novel and
      promising use of the TandemHeart as a bridge to myectomy.

PMID- 22364992
TI  - Giant posterolateral left ventricular aneurysm diagnosed 6 weeks after incomplete
      surgical revascularization.
AB  - We report the surgical repair of a true left ventricular aneurysm diagnosed 6
      weeks after incomplete surgical revascularization.

PMID- 22364993
TI  - Spontaneous ear hemorrhage during cardiac surgery.
AB  - A 79-year-old patient who underwent mitral valve replacement experienced
      prolonged elevated central venous pressure associated with poor venous return
      during a cardiopulmonary bypass. After the procedure, the patient was noted to
      have spontaneous bleeding from the left ear. Otolaryngologic examination in the
      operating room showed no trauma in the exterior auditory canal and suggested that
      the hemorrhage was related to a superior vena cava syndrome and anticoagulation
      during the cardiopulmonary bypass. Determinants and management considerations of
      poor venous return, including maintenance of cerebral perfusion pressure, are
      discussed.

PMID- 22364994
TI  - Antibiotic-impregnated beads for the treatment of aortic graft infection.
AB  - Infection of a prosthetic graft after replacement of the ascending aorta is an
      uncommon but life-threatening complication of surgery. We report the use of
      antibiotic-impregnated calcium sulfate beads in a patient with ascending aortic
      graft infection to provide localized, high-dose therapy to the infected region.
      Perigraft placement of antibiotic beads provides an alternative method for the
      treatment of aortic graft infection.

PMID- 22364995
TI  - Surgical treatment of transposition of the great arteries with bilateral
      intramural coronary arteries.
AB  - A 33-day-old neonate with transposition of the great arteries, ventricular septal
      defect, and intramural course of both coronary arteries underwent successful
      arterial switch repair. At a follow-up time of 36 months, left ventricular
      function and coronary arterial anatomy at angiography were normal. Optimal
      treatment of such rare coronary arterial abnormality may allow functional and
      anatomic results comparable to usual coronary arterial patterns in transposition
      of the great arteries.

PMID- 22364996
TI  - Airway gastric fistula after esophagectomy for esophageal cancer.
AB  - Airway gastric fistula formation is a rare and complex complication after
      esophagectomy. Clinical presentations vary, making a uniform approach to
      treatment not possible. Recently, nonsurgical approaches have been reported using
      various types of airway stents. However, the usefulness of airway stenting in the
      treatment of airway gastric fistula is relatively unknown. We present a patient
      with hemoptysis, respiratory failure, and an enlarging left mainstem
      bronchogastric fistula after esophagectomy. The patient's symptoms were
      temporized by the placement of a silicone stent.

PMID- 22364997
TI  - Mediastinal mature teratoma with rupture into pleural cavity due to blunt trauma.
AB  - We report a rare case of mediastinal mature teratoma with rupture due to blunt
      trauma. A 15-year-old boy had received a strong head-butt in the left upper chest
      wall and was admitted with the sudden onset of left-sided severe chest pain and
      dyspnea. Chest computed tomography (CT) scan on admission revealed a
      heterogeneous mass lesion in the anterior mediastinum. The contrast-enhanced CT
      scans obtained 2 days after admission showed not only mediastinal mass lesion but
      also left pleural effusion. On the radiologic finding at 5 months later, the
      lesion became larger and was thought to be a typical mediastinal mature teratoma.
      The patient underwent extirpation of the tumor. Microscopically, the tumor was
      typically composed of adult-type tissues and was confirmed to be mature teratoma.

PMID- 22364998
TI  - Conservative management of traumatic lung hernia.
AB  - Traumatic lung hernia is a rare entity. The majority of cases reported in the
      literature have been treated surgically with early thoracotomy to prevent
      strangulation of pulmonary tissue. We report the case of a 63-year-old patient
      who experienced a 20-foot fall, causing multiple rib fractures with a lung hernia
      that was managed conservatively for 48 hours followed by spontaneous resolution
      of the herniated pulmonary segment. There is a need to review the indications for
      surgical versus conservative approach in the management of posttraumatic lung
      hernia.

PMID- 22364999
TI  - Thoracic outlet syndrome caused by fibrous dysplasia of the first rib.
AB  - Fibrous dysplasia causing thoracic outlet syndrome is rare. A 41-year-old woman
      presented with neurogenic thoracic outlet syndrome with imaging that demonstrated
      a large tumor of her proximal left first rib. Transaxillary excision was
      unsuccessful due to involvement of the subclavian vasculature and brachial
      plexus. Subsequent posterolateral thoracotomy and resection of her first rib
      revealed fibrous dysplasia. Thoracotomy should be considered in these cases for
      optimal vascular control and identification of thoracic outlet anatomy.

PMID- 22365000
TI  - Primary de novo angiosarcoma of the pleura.
AB  - Primary angiosarcoma of the pleura is an extremely rare soft tissue tumor with a
      poor prognosis. We report a case of primary angiosarcoma of the pleura in which
      the patient was admitted for dyspnea and massive bilateral recurrent hemothorax
      with fatal outcome. We also review the literature.

PMID- 22365001
TI  - Acute aortic valve thrombosis secondary to recombinant factor VIIa.

PMID- 22365002
TI  - Saccular aneurysm of the descending aorta after surgery for aortic arch
      interruption.

PMID- 22365003
TI  - Iatrogenic tracheal injury.

PMID- 22365004
TI  - A novel approach to ventricular rupture: clinical needs and surgical technique.
AB  - Cardiac rupture is a life-threatening event that often occurs after myocardial
      infarction and is often associated with significant death. Pericardiocentesis
      provides hemodynamic short-term improvement; however, patients with cardiac
      rupture require an emergency operation. This report describes a new procedure
      used to repair left ventricle free wall rupture after myocardial infarction. The
      technique described repairs the rupture off-pump and without the need for
      suturing. Midterm results demonstrate the feasibility and durability of this
      procedure.

PMID- 22365005
TI  - Transbrachial endoclamping of the graft for descending aortic aneurysm after the
      elephant trunk procedure.
AB  - Patients who have undergone the elephant trunk procedure because of aortic
      dissection may subsequently present with a descending aortic aneurysm. We
      describe the technique of "endograft aortic control by inflating a compliant
      aortic occlusion balloon," in which a balloon is placed in the proximal
      descending aortic graft without cross-clamping to avert problems of hemorrhage at
      the second stage of the elephant trunk procedure.

PMID- 22365006
TI  - Perventricular device closure of patent ductus arteriosus: a secondary chance.
AB  - Transcatheter closure is the mainstay of treatment for patent ductus arteriosus
      (PDA) in the pediatric patient but it is technically challenging and does not
      always succeed, especially in a younger age child with a large PDA. We present a
      technique of using a transesophageal echocardiogram-guided minimally invasive
      perventricular closure for the pediatric patient with a large PDA who failed
      transcatheter closure.

PMID- 22365007
TI  - Use of a pedicled omental flap in the treatment of chest wall tuberculosis.
AB  - The most effective way to treat the chest wall tuberculosis is to fill the
      residual space with a muscle flap after complete resection of the lesion.
      However, in some situations a muscle flap cannot be used. The greater omentum has
      been widely used for reconstruction and the treatment of infections. We describe
      our technique of using a pedicled omental transposition flap in the management of
      chest wall tuberculosis for closing the dead space created by excision of the
      lesion.

PMID- 22365008
TI  - Safety of magnetic resonance imaging in cardiac surgery patients: annuloplasty
      rings, septal occluders, and transcatheter valves.

PMID- 22365010
TI  - Impact of annuloplasty device aggressiveness on leaflet coaptation.

PMID- 22365012
TI  - The surgical treatment of hyperhidrosis.

PMID- 22365014
TI  - Aortic root reimplantation for isolated sinus of valsalva aneurysm in the patient
      with Marfan's syndrome.
AB  - We describe an isolated extracardiac unruptured acquired aneurysm in the right
      coronary sinus of Valsalva, which was seen in a 55-year-old woman with Marfan's
      syndrome. The patient underwent aortic root replacement using a reimplantation
      technique. Pathologic examination revealed absence of the medial elastic fiber of
      the aortic wall of the normal sinus of Valsalva. This result supports the
      preference of entire root replacement instead of patch repair of the affected
      sinus for the isolated aneurysm in 1 sinus of Valsalva in a patient with Marfan's
      syndrome.

PMID- 22365015
TI  - Replacement of a stented biologic prosthesis within an aortic valved conduit.
AB  - A 68-year-old man was referred for severe aortic regurgitation 10 years after
      aortic root replacement with a valved conduit containing a stented bioprosthesis
      that had been sutured inside of the vascular tube graft, rather than at its
      extremity. Because of this simple modification of the Bentall concept, replacing
      the prosthetic valve within the aortic conduit was easy and uneventful.

PMID- 22365016
TI  - Left atrial wall hematoma as a consequence of percutaneous coronary angioplasty.
AB  - Intramural left atrial dissection and hematoma as a complication of a coronary
      stenting procedure is a very rare entity. We report the case of a 73-year-old man
      who underwent percutaneous coronary angioplasty for a severe stenosis of the left
      circumflex coronary artery, complicated by a left atrial intramural hematoma, and
      was successfully treated with via a minimally invasive port-access surgical
      approach.

PMID- 22365017
TI  - Total arch replacement for acute aortic dissection (Stanford A) in a patient with
      hemophilia A.
AB  - As a result of improvements in medical management, patients suffering from
      hemophilia have a life expectancy approaching that of the normal population. An
      increased life expectancy, however, brings an increased risk of developing age
      related disorders. Several article have reported elective cardiac operations
      successfully performed on hemophiliacs. To our knowledge, there are no articles
      describing such patients undergoing emergent aortic surgery. Our report describes
      the successful management of an individual with hemophilia A undergoing emergent
      total arch replacement for acute aortic dissection (Stanford A). We used a
      continuous infusion of factor VIII concentrate during the perioperative period.
      The patient was discharged without bleeding complications.

PMID- 22365018
TI  - A double-orifice tricuspid valve associated with a divided right atrium.
AB  - Right atrioventricular valve duplication is a rare congenital anomaly with only
      isolated cases of a double-orifice tricuspid valve having been described. This
      article presents a case of the surgical repair of a double-orifice tricuspid
      valve associated with a divided right atrium, a ventricular septal defect, and
      Wolff-Parkinson-White syndrome.

PMID- 22365019
TI  - A new option for autologous anterior chest wall reconstruction: the composite
      thoracodorsal artery perforator flap.
AB  - Sternal chondrosarcoma is rare and often requires total or subtotal sternectomy.
      The authors describe the case of a 70-year-old man with sternoclavicular joint
      chondrosarcoma who underwent subtotal sternectomy with partial resection of the
      two clavicles and anterior arches of first to third right ribs. Anterior chest
      wall reconstruction was performed with a composite thoracodorsal artery
      perforator free flap with sixth and seventh ribs vascularized on serratus muscle.
      The postoperative course was uneventful. Seven months after surgery, the patient
      was doing well. This surgical procedure is a new option for autologous
      reconstruction without prosthetic material after extensive sternectomy.

PMID- 22365020
TI  - Allogenic sternal transplant after sternectomy for metastasis of ovarian
      carcinoma.
AB  - Sternal metastasis from ovarian carcinoma is extremely rare. We report a case of
      a young woman in whom a single metastasis at the level of the upper portion of
      the sternum developed. Surgical excision of the sternum was performed with
      replacement by a sternal allograft stabilized by titanium plates and transosseous
      high-tension sutures. With this simple and reproducible technique, we obtained a
      stable and dynamic reconstruction of the sternoclavicular joints and shoulder
      girdle. The use of a sternal allograft provides excellent functional and cosmetic
      results. The implantation technique is simple and reproducible.

PMID- 22365021
TI  - Myxoma in the left atrium?

PMID- 22365022
TI  - Anomalous right coronary artery arising from the pulmonary artery.

PMID- 22365023
TI  - Left atrial reduction plasty: a novel technique.
AB  - We describe a novel technique of left atrial volume reduction in a patient
      presenting with severe dyspnea from severe mitral insufficiency, giant left
      atrium, and compressive symptoms of dysphagia and dysphonia. Resection involved
      circumferential excision of the left atrium anterior to the pulmonary venous
      vestibule and posterior to the mitral valve and fossa ovalis, including the left
      atrial appendage. A chordal-sparing bioprosthetic mitral valve replacement,
      tricuspid valve annuloplasty, and coronary bypass were also performed.
      Significant reduction of left atrial volume by 50% was achieved and clinical
      resolution of compressive symptoms was seen at 6-month follow-up.

PMID- 22365024
TI  - Metformin-associated lactic acidosis masquerading as ischemic bowel.

PMID- 22365025
TI  - From the outside looking in.

PMID- 22365026
TI  - Nature versus nurture in gout: a twin study.
AB  - BACKGROUND: Gouty arthritis (gout) is the most common inflammatory arthritis in
      the United States and several other countries. Some rare forms of gout have a
      known genetic basis, but the relative importance of genetic factors on the risk
      for the lifetime prevalence of gout is not clear. METHODS: We performed a
      heritability analysis for hyperuricemia and gout among 514 unselected, all-male
      twin pairs who were a part of the National Heart, Lung, and Blood Institute twin
      study, a prospective observational cohort study. Statistical analyses were
      performed using structural equation models and maximum likelihood methods. The
      covariates used for adjustment in the structural equation models were identified
      using bivariate logistic regressions. RESULTS: The study population included 253
      monozygotic (MZ) and 261 dizygotic (DZ) twin pairs, aged 48 (+/-3) years at
      baseline and followed for a mean of 34 years. The lifetime prevalence of gout did
      not differ between MZ and DZ twins. The concordance of hyperuricemia was 53% in
      MZ and 24% in DZ twin pairs (P<.001). Models that quantified the relative
      contribution of genetic and environmental factors on phenotypic variance showed
      that individual variability in gout was substantially influenced by environmental
      factors shared between co-twins and not by genetic factors. In contrast,
      individual differences in hyperuricemia were influenced significantly by genetic
      factors. CONCLUSION: Hyperuricemia is a genetic trait. Outside the context of
      rare genetic disorders, risk for gout is determined by the environment. This has
      implications for prevention and treatment approaches.

PMID- 22365027
TI  - Sono-synthesis of core-shell nanocrystal (CdS/TiO2) without surfactant.
AB  - A core-shell nanocomposite (CdS/TiO(2)) was synthesized at relatively low
      temperature (70 degrees C) with small particle sizes (~11 nm). First, CdS
      nanoparticles were prepared by a combination of ultrasound and new micro-emulsion
      (O/W) without surfactant. Then the synthesized CdS was easily combined with
      TiO(2) under sonication. The formation of uniform surface layer of TiO(2) with
      depths of 0.75-1.1 nm on the CdS led to an increase of particle size. Ultrasonic
      irradiation can control the hydrolysis and condensation of titanium tetra
      isopropoxide (TTIP) and the formation of TiO(2) shell around the CdS core. This
      technique avoids some of the problems that exist in conventional microemulsion
      synthesis such as the presence of different additives and calcinations. It was
      found that nanocomposite particles extend the optical absorption spectrum into
      the visible region in comparison with pure TiO(2) and pure CdS. In addition, a
      larger depth of TiO(2) led to a red-shift of the absorption band in
      nanocomposite. The characterization of nanocomposites has been studied by HRTEM,
      TEM, XRD, EDAX, BET and, UV-vis.

PMID- 22365028
TI  - The crews are key!: specialized EMS team deployment yields best results.

PMID- 22365029
TI  - Stuck in a rut: EMS has opportunity for system redesign.

PMID- 22365030
TI  - Little things: stuff we can learn from 'ambulance drivers'.

PMID- 22365031
TI  - Easy as E-C-G: teach 12-lead interpretation in 3 easy phases.

PMID- 22365032
TI  - More than chest pain: providers treat patient with thoracic aortic dissection.

PMID- 22365034
TI  - Evolution or revolution: EMS industry faces difficult changes.

PMID- 22365035
TI  - EMS royal flush: Jersey City Medical Center EMS reinvents itself & achieves five
      major national EMS recognitions.

PMID- 22365036
TI  - No pulse?: check for a left-ventricular assist device.

PMID- 22365037
TI  - First 100 early endometrial cancer cases treated with laparoendoscopic single
      site surgery: a multicentric retrospective study.
AB  - OBJECTIVE: We sought to assess feasibility and perioperative outcomes for
      laparoendoscopic single-site surgery (LESS) in early endometrial cancer. STUDY
      DESIGN: This was a retrospective multicentric study of 100 early endometrial
      cancer cases undergoing LESS from July 2009 through July 2011. RESULTS: All
      patients underwent total hysterectomy and bilateral salpingo-oophorectomy by
      LESS. Pelvic and paraaortic lymphadenectomy were performed in 48 and 27 patients,
      respectively. A median of 16 pelvic lymph nodes (range, 1-33) and 7 paraaortic
      lymph nodes (range, 2-28) were retrieved. Both median operative time (129
      minutes; range, 45-321) and estimated blood loss (70 mL; range, 10-500) were
      greater when staging lymphadenectomy was performed (P values = .001). Four
      intraoperative and 4 postoperative complications were observed. Conversion to
      standard laparoscopy and laparotomy was necessary for completion of 1 case each.
      Patients responded positively regarding cosmetic result and minimal postoperative
      pain control. CONCLUSION: LESS further minimizes the invasive nature of surgery
      and is feasible for treatment of early-stage endometrial cancer.

PMID- 22365038
TI  - The expression of antioxidant enzymes in a mouse model of fetal alcohol syndrome.
AB  - OBJECTIVE: Superoxide dismutase, glutathione peroxidase, and catalase prevent
      cellular damage produced by free radicals. Our objective was to evaluate if
      prenatal alcohol exposure decreased the expression of antioxidant enzymes in the
      brain, liver, or placenta of fetal mice. STUDY DESIGN: Timed, pregnant C57BL6/J
      mice were treated on gestational day 8 with intraperitoneal injection of alcohol
      (0.03 mL/g) or saline (control). Fetuses were harvested on gestational day 18.
      Fetal brain, liver, and placenta were analyzed for mRNA expression of superoxide
      dismutase, glutathione peroxidase, and catalase by real-time polymerase chain
      reaction, with 18S RNA used as reference. RESULTS: Superoxide dismutase,
      glutathione peroxidase, and catalase expression was lower in fetal brains exposed
      to alcohol with no differences detected in the liver or placenta between the 2
      groups. CONCLUSION: Maternal alcohol consumption causes a decrease in superoxide
      dismutase, glutathione peroxidase, and catalase expression in the fetal brain.
      This may explain the long-term neurologic findings in fetal alcohol syndrome.

PMID- 22365039
TI  - Levator avulsion using a tomographic ultrasound and magnetic resonance-based
      model.

PMID- 22365041
TI  - [Promoting prevention policy].

PMID- 22365040
TI  - Impact of high glucose and transforming growth factor-beta on bioenergetic
      profiles in podocytes.
AB  - Diabetic nephropathy is the most common cause of chronic renal failure in
      industrialized countries. Depletion of podocytes plays an important role in the
      progression of diabetic glomerulopathy. Various factors in the diabetic milieu
      lead to serious podocyte stress driving the cells toward cell cycle arrest
      (p27(Kip1)), hypertrophy, detachment, and apoptosis. Mitochondria are responsible
      for oxidative phosphorylation and energy supply in podocytes. Recent studies
      indicated that mitochondrial dysfunction is a key factor in diabetic nephropathy.
      In the present study, we investigated metabolic profiles of podocytes under
      diabetic conditions. We examined oxygen consumption rates (OCRs) and oxidative
      phosphorylation complex activities in murine podocytes. Cells were exposed to
      high glucose for 48 hours, cultured for 10 passages under high-glucose conditions
      (30 mmol/L), or incubated with transforming growth factor-beta (5 ng/mL) for 24
      hours. After prolonged exposure to high glucose, podocytes showed a significantly
      increased OCR at baseline and also a higher OCR after addition of oligomycin,
      indicating significant changes in mitochondrial energy metabolism. Higher OCRs
      after inhibition of respiration by rotenone also indicated changes in
      nonmitochondrial respiration. Podocytes stimulated with a proapoptotic
      concentration of transforming growth factor-beta displayed similar bioenergetic
      profiles, even with decreased citrate synthase activity. In all tested
      conditions, we found a higher cellular nicotinamide adenine dinucleotide content
      and changes in activities of respiratory chain complexes. In summary, we provide
      for the first time evidence that key factors of the diabetic milieu induce
      changes in glucose metabolism and mitochondrial function in podocytes.

PMID- 22365042
TI  - [The publication of scientific articles plays a key role in the construction of
      health problems and their national and international visibility].

PMID- 22365043
TI  - [Adapting medical practices to the field: pregnancy and HIV in French Guyana and
      Saint-Martin].
AB  - Because of its high prevalence, HIV in pregnancy is a major public health issue
      in French Guyana and Saint Martin, particularly since the risk of transmission to
      the child can be significantly reduced through pharmacological treatment. Most of
      the HIV-infected women in these areas are immigrants living in highly precarious
      circumstances. This study examines the capacity of the healthcare system to adapt
      to the specific social characteristics of overseas regions, focusing in
      particular on perceptions of the risks associated with pregnancy among HIV
      infected women and the social inequalities affecting adherence to HIV treatment.
      Semi-structured interviews were conducted in Cayenne, Saint-Laurent du Maroni and
      Saint-Martin with 19 HIV-infected women and 54 social and health care
      professionals. Observations (medical consultations, therapeutic education
      consultations, discussion groups, medical meetings) were also conducted to
      complete the data set. The results show that professionals tend to use the most
      significant concern expressed by HIV-infected women - i.e. the risk of
      transmitting their infection to their child - as an opportunity to promote the
      active involvement of patients in their own care and the health care of their
      children by encouraging them to adhere to their treatment. The study found that
      professionals seek to lessen the impact of social inequalities on patient
      adherence to the treatment in a context of social stigmatization linked to the
      particular status of their patients as HIV-infected women, undocumented migrants,
      and ethnic minority members. The example of HIV in pregnancy illustrates the
      capacity of the healthcare system to reduce the impact of social inequalities on
      health and highlights the significant negative impact that a reduced commitment
      to this issue would have.

PMID- 22365044
TI  - [Determinants of street drug use in urban areas].
AB  - A descriptive and analytical cross-sectional study was conducted to assess street
      drug use in an urban setting. The study was conducted in Abidjan city center
      (Adjame). The general aim of the study was to contribute to the fight against
      street drug consumption by identifying the determinants of drug use. The
      objectives of this paper are to describe the socio-demographic characteristics of
      street drug users, to determine the type of drugs purchased, and to identify the
      factors influencing drug purchase. Based on a sample of 300 individuals, the
      study found that the use of street drugs is a widespread phenomenon, as shown by
      its prevalence in the surveyed population (216 individuals out of a total of 300,
      i.e. 72% of the surveyed population). The study found that most drug users were
      young, male (32%) and worked in the informal sector. More than half of the drug
      users (58%) had a monthly income below 50,000 CFA and had no health insurance.
      The low cost of drugs was found to be the main reason for drug use (69%). The
      most commonly used drugs were analgesics (75%), antimalarial drugs (72%) and
      antibiotics (48%). Because of the lack of medical knowledge of drug sellers, drug
      users are exposed to serious health risks. The results of this study suggest the
      need for greater public awareness of the dangers of street drugs and emphasize
      the importance of promoting access to essential generic drugs.

PMID- 22365045
TI  - [Perceived quality of care among health professionals at the University Hospital
      of Oran (EHUO)].
AB  - Created in 2003 as a profit organization, the University Hospital of Oran
      (Etablissement Hospitalier Universitaire d'Oran-EHUO) is currently in the process
      of developing a 'Quality' project aimed at assessing staff perception of quality.
      20% of staff members representing the various professional categories working at
      EHUO (medical, nursing and administrative staff) were selected using quota
      sampling. Face-to-face interviews were conducted in March 2009 with 117 staff
      members from 25 medical and 5 non-medical units. The average length of service
      among medical and administrative staff was higher than the average length of
      service of nursing staff (8.3 vs 5.8 years; p = 0.9 Kruskal-Wallis H test). In
      discussing the question of quality, it was found that all categories of staff
      emphasized their specific professional experiences, standards and frames of
      reference. All staff members showed a greater preference for the various
      dimensions of the "are process" (mostly physicians and nurses rather than
      administrative staff (p=0.01)) than for the "structure" or "organization"
      components of the quality plan. In this sense, there appears to be a greater
      focus on technical rather than management aspects, as shown by the fact that two
      thirds of staff members were ill-informed about the hospital's quality assurance
      program (quality management, blood safety, complaints management...). While they
      appeared to be fully supportive of audit and certification procedures, 50% of
      health staff members were reluctant to support patient involvement in the
      management of the 'Quality' project. Finally, there appears to be a lack of
      awareness of quality concepts, standards and methodologies among hospital staff.
      This study suggests that there is a need for greater awareness, further training,
      and greater monitoring of practices based on concrete actions.

PMID- 22365046
TI  - [Highly pathogenic influenza pandemic: results of a feasibility study in a
      general practice (SIMUGRIP-MG2)].
AB  - The French Pandemic Influenza Plan ("Plan National de Prevention et de Lutte
      Pandemie Grippale") places general practitioners at the heart of the provision of
      care to patients through consultations and house calls. The purpose of this study
      was to determine whether GP practices are able to provide treatment to flu
      patients within their premises in the event of a highly pathogenic influenza
      pandemic. A simulation exercise conducted in a GP practice (SIMUGRIP-MG2) was
      carried out in the autumn of 2009. 3 general practitioners, the practice
      secretary, 33 patients and care staff took part in the exercise during a half day
      of practice. The study found that the quality of some hygiene practices and
      procedures was inadequate: the duration of handwashing was too short (mean: 11.8
      seconds), gloves were not worn, and FFP2 masks were often handled. The study
      found that the implementation of these procedures required increased effort and
      attention from GPs. It was also found that this type of consultation requires
      additional preparation time (refitting, supply of materials) and generates
      additional costs (linked, for example, to storage issues). In seeking to improve
      the quality of care provided to infected patients in the event of an influenza
      pandemic, several factors must be considered, including recent data on the
      effectiveness of countermeasures, additional training to improve hygiene
      practices, and infrastructure modernization to improve ergonomics in GP
      practices.

PMID- 22365047
TI  - [A simulation exercise in a flu clinic].
AB  - A simulation exercise aimed at assessing the management and provision of
      ambulatory care in the context of a highly pathogenic influenza pandemic was
      conducted in a specifically dedicated consultation center (Centre de Consultation
      Dedie (CCD) a la grippe) based on official French guidelines. The exercise was
      carried out in a school in Paris equipped to simulate a "flu clinic". 3
      practitioners provided treatment lasting 2 hours to nursing students acting as
      patients.   The exercise highlighted a number of major organizational issues.
      Staff were found to be unable to manage the center and to perform patient
      transfers; face masks were not routinely and consistently worn by doctors and
      patients; and communication between professionals within the clinic was limited. 
      The exercise showed that much remains to be done to ensure that "flu clinics"
      are effective and functional. The results suggest that the exercise will need to
      be repeated on a larger scale and over a longer period.

PMID- 22365050
TI  - Capucin does not modify the toxicity of a mutant Huntingtin fragment in vivo.
AB  - Genes selectively expressed in the striatum may be involved in the preferential
      vulnerability of striatal neurons to Huntington's disease (HD). Here, we
      investigated whether perturbations of Capucin expression, which is enriched in
      the striatum and downregulated in Huntington's disease models, could modify the
      neurotoxicity induced by the injection of a lentiviral vector encoding a short N
      terminal fragment of mutant Huntingtin (mHtt) into the mouse striatum. Neither
      constitutive Capucin deficiency in knockout mice nor lentiviral vector-mediated
      Capucin overexpression in the striatum of adult wild type mice significantly
      modified vulnerability to the mHtt fragment in vivo, suggesting that Capucin has
      no impact on mHtt toxicity.

PMID- 22365049
TI  - Longitudinal imaging pattern analysis (SPARE-CD index) detects early structural
      and functional changes before cognitive decline in healthy older adults.
AB  - This article investigates longitudinal imaging characteristics of early cognitive
      decline during normal aging, leveraging on high-dimensional imaging pattern
      classification methods for the development of early biomarkers of cognitive
      decline. By combining magnetic resonance imaging (MRI) and resting positron
      emission tomography (PET) cerebral blood flow (CBF) images, an individualized
      score is generated using high-dimensional pattern classification, which predicts
      subsequent cognitive decline in cognitively normal older adults of the Baltimore
      Longitudinal Study of Aging. The resulting score, termed SPARE-CD (Spatial
      Pattern of Abnormality for Recognition of Early Cognitive Decline), analyzed
      longitudinally for 143 cognitively normal subjects over 8 years, shows functional
      and structural changes well before (2.3-2.9 years) changes in neurocognitive
      testing (California Verbal Learning Test [CVLT] scores) can be measured.
      Additionally, this score is found to be correlated to the [(11)C] Pittsburgh
      compound B (PiB) PET mean distribution volume ratio at a later time. This work
      indicates that MRI and PET images, combined with advanced pattern recognition
      methods, may be useful for very early detection of cognitive decline.

PMID- 22365051
TI  - In situ and tomographic observations of defect free channel formation in ion
      irradiated stainless steels.
AB  - The effects of heavy-ion irradiation on dislocation processes in stainless steels
      were investigated using in situ irradiation and deformation in the transmission
      electron microscope as well as post mortem electron tomography to retrieve
      information on the three-dimensional dislocation state. Irradiation-induced
      defects were found to pose a strong collective barrier to dislocation motion,
      leading to dislocation pileups forming in grain interiors and at grain
      boundaries. The passage of multiple dislocations along the same slip plane
      removes the irradiation defects and leads to the eventual formation of a defect
      free channel. These channels are composed of densely tangled dislocation networks
      which line the channel-matrix walls as well as residual dislocation debris in the
      channel interiors. The structures of the dislocation tangles were found to be
      similar to those encountered in later stages of deformation in unirradiated
      materials, with the exception that they developed earlier in the deformation
      process and were confined to the defect free channels. Also, defect free channels
      were found to widen through both source widening as well as complex cross-slip
      mechanisms.

PMID- 22365054
TI  - Application of nanoLC-ESI-TOF-MS for the metabolomic analysis of phenolic
      compounds from extra-virgin olive oil in treated colon-cancer cells.
AB  - Crude phenolic extracts (PE) have been obtained from naturally bearing Spanish
      extra-virgin olive oil (EVOO) showing different polyphenol families such as
      secoiridoids, phenolic alcohols, lignans, and flavones. EVOO-derived complex
      phenols (especially from the Arbequina variety olive) have been shown to suppress
      cell growth of SW480 and HT29 human colon adenocarcinoma cell lines. Inhibition
      of proliferation by EVOO-PE Arbequina variety extract was accompanied by
      apoptosis in both colon-cancer-cell lines and a limited G2M cell-cycle arrest in
      the case of SW480 cells. The metabolized compounds from EVOO-PE in culture medium
      and cytoplasm of both cell lines were analyzed using nano-liquid chromatography
      (nanoLC) coupled with electrospray ionization-time-of-flight-mass spectrometry
      (ESI-TOF-MS). The results showed many phenolic compounds and their metabolites
      both in the culture medium as well as in the cytoplasm. The main compounds
      identified from EVOO-PE were hydroxylated luteolin and decarboxymethyl oleuropein
      aglycone.

PMID- 22365055
TI  - Persistence of high sustained antibodies to enzyme replacement therapy despite
      extensive immunomodulatory therapy in an infant with Pompe disease: need for
      agents to target antibody-secreting plasma cells.
AB  - With the advent of enzyme replacement therapy (ERT) with alglucosidase alfa
      (rhGAA, Myozyme(r)) for Pompe disease, the clinical course of the disease has
      changed. We have previously described the poor outcome in cross reactive
      immunologic material (CRIM)-negative and high-titer CRIM-positive (HTCP) patients
      secondary to high sustained antibody titers (HSAT) which effectively neutralize
      ERT efficacy. Various immunomodulation strategies are being explored to diminish
      the immune response to ERT. However, once HSAT are formed, tolerization therapy
      has uniformly failed to lower antibody titers. Here we describe a case in which
      immunomodulation over a prolonged period of 28 months with cyclophosphamide,
      intravenous immunoglobulin, plasmapheresis, increased doses of rhGAA and
      rituximab failed to lower antibody titers and resulted in continued clinical
      decline in an infantile Pompe disease patient treated with ERT. Thus, it appears
      that the failure to target the antibody-secreting plasma cells responsible for
      HSAT led to a failure of tolerance induction. This is the first report using this
      combination of agents over a very extensive period of time with no success.

PMID- 22365056
TI  - Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness:
      comparison with nerve fiber layer and optic nerve head.
AB  - PURPOSE: To determine the diagnostic performance of macular ganglion cell-inner
      plexiform layer (GCIPL) thickness measured with the Cirrus high-definition
      optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm
      (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early
      glaucoma and to compare it with that of peripapillary retinal nerve fiber layer
      (RNFL) thickness and optic nerve head (ONH) measurements. DESIGN: Evaluation of
      diagnostic test or technology. PARTICIPANTS: Fifty-eight patients with early
      glaucoma and 99 age-matched normal subjects. METHODS: Macular GCIPL and
      peripapillary RNFL thicknesses and ONH parameters were measured in each
      participant, and their diagnostic abilities were compared. MAIN OUTCOME MEASURES:
      Area under the curve (AUC) of the receiver operating characteristic. RESULTS: The
      GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal
      (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918).
      There were no significant differences between these AUCs and those of inferior
      quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical
      cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area
      (0.910), all P>0.05. CONCLUSIONS: The ability of macular GCIPL parameters to
      discriminate normal eyes and eyes with early glaucoma is high and comparable to
      that of the best peripapillary RNFL and ONH parameters. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosure may be found after the references.

PMID- 22365057
TI  - Validation and cost-effectiveness of a home-based screening system for amblyopia.
AB  - PURPOSE: To investigate the cost-effectiveness of a novel home-based screening
      system for amblyopia and amblyogenic risk factors. DESIGN: Evaluation of
      diagnostic test or technology. PARTICIPANTS: Two thousand four hundred forty-two
      preschoolers 3 to 6 years of age from 10 kindergartens randomly selected from
      Guangzhou participated in the study in 2009. METHODS: Preschoolers were assessed
      for amblyopia and amblyogenic risk factors by their parents using the home-based
      screening system and were re-evaluated by professionals who conducted a
      comprehensive eye examination. MAIN OUTCOME MEASURES: Sensitivity, specificity,
      positive predictive value, negative predictive value, and the cost-benefit of the
      home-based screening system were calculated by comparing the results from the
      home-assessed model and those from the professional evaluation. RESULTS: Three
      thousand three hundred children were invited to participate in the study, and
      2308 (1216 boys and 1092 girls) completed all of the procedures. Twenty-four
      amblyopes were found by professional examinations. Fifteen of these amblyopes had
      not been diagnosed previously, and 12 of them were detected by the home
      assessment model. The sensitivity, specificity, positive predictive value, and
      negative predictive value were 80.0%, 94.1%, 8.2%, and 99.9%, respectively.
      Professional examinations cost an average of US $1131.00 per case of amblyopia
      detected, whereas the cost was only US $266.00 per case for the home-based
      method. For amblyogenic factors, 50, 87, and 96 children were classified into
      grade I, II, or III according to the professional examinations. The corresponding
      numbers in the home-based system were 23, 29, and 15, respectively. Accordingly,
      the true positive rates were 46.0%, 33.3%, and 15.6% for each grade. CONCLUSIONS:
      The home-based amblyopia screening system was found to be a simple, effective,
      and cost-beneficial method for amblyopia screening and amblyogenic risk factors.
      The approach offers a practical option for developing areas with large
      populations. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 22365059
TI  - The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule
      for diagnosing glaucomatous optic disc damage.
AB  - PURPOSE: To determine the accuracy with which the optic disc can be diagnosed as
      normal or glaucomatous according to the ISNT rule, whereby, in the normal eye,
      the neuroretinal rim area follows the order inferior (I) > superior (S) > nasal
      (N) > temporal (T). DESIGN: Prospective, cross-sectional, observational, case
      series. PARTICIPANTS: Fifty-one normal individuals and 78 individuals with open
      angle glaucoma exhibiting field loss (median mean deviation, -4.37 dB;
      interquartile range [IQR], -2.10 to -7.96 dB; median pattern standard deviation,
      5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on
      the basis of the appearance of the optic disc and of the corresponding visual
      field. METHODS: Stereoscopic optic disc photographs, acquired for each
      individual, were digitized at high resolution and analyzed using a digital, quad
      buffered, stereoscopic viewing system in which a Z screen was used to dissociate
      the images to the 2 eyes of the observer. Three expert observers, trained to
      fellowship standard in glaucoma, independently undertook planimetry of the
      neuroretinal rim and of the disc margin from 1 eye of each individual, using a
      cursor moving in stereoscopic space to minimize parallax errors. Software
      automatically calculated the neuroretinal rim area in 10 degrees , 30 degrees ,
      40 degrees , and 90 degrees  segments. For the ISNT rule to be obeyed, the 3
      Boolean comparisons of the neuroretinal rim area, I>S, S>N, and N>T, had to be
      true. If any of the comparisons returned false, the rule was considered not to
      have been obeyed. Values were compared at a precision of 0.0001 mm(2). MAIN
      OUTCOME MEASURES: The outcome of the ISNT rule in terms of the 3 Boolean
      comparisons of the neuroretinal rim area was specified in terms of the
      sensitivity, specificity, and hence, the positive and negative likelihood ratios.
      RESULTS: Based on the ISNT rule being obeyed for 10 degrees  segments, the
      positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval
      [CI], 0.99-1.25), 1.07 (95% CI, 0.94-1.21), and 1.06 (95% CI, 0.96-1.18),
      respectively. It was similar for the other segment sizes. Variants of the rule
      were not appreciably better. CONCLUSIONS: The ISNT rule has limited utility in
      the diagnosis of open-angle glaucoma.

PMID- 22365058
TI  - Ganglion cell loss in relation to visual disability in multiple sclerosis.
AB  - PURPOSE: We used high-resolution spectral-domain optical coherence tomography (SD
      OCT) with retinal segmentation to determine how ganglion cell loss relates to
      history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning,
      visual function, and vision-related quality of life (QOL) in multiple sclerosis
      (MS). DESIGN: Cross-sectional study. PARTICIPANTS: A convenience sample of
      patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes).
      Among MS eyes, 87 had a history of ON before enrollment. METHODS: The SD-OCT
      images were captured using Macular Cube (200*200 or 512*128) and ONH Cube 200*200
      protocols. Retinal layer segmentation was performed using algorithms established
      for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform
      layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer
      nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus
      control eyes and MS ON versus non-ON eyes. The relation between changes in
      macular thickness and visual disability was also examined. MAIN OUTCOME MEASURES:
      The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity
      (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25
      item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10
      Item Neuro-Ophthalmic Supplement composite score. RESULTS: Macular RNFL and
      GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P =
      0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary
      RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were
      significantly correlated with VA (P<=0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA
      (P<=0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL
      (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most
      strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL
      scores; GCL+IPL thinning was significant even accounting for macular RNFL
      thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL). CONCLUSIONS: We
      demonstrated that GCL+IPL thinning is most significantly correlated with both
      visual function and vision-specific QOL in MS, and may serve as a useful
      structural marker of disease. Our findings parallel those of magnetic resonance
      imaging studies that show gray matter disease is a marker of neurologic
      disability in MS. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure
      may be found after the references.

PMID- 22365060
TI  - Potential reach of effective smoking prevention programmes in vocational schools:
      determinants of school directors' intention to adopt these programmes.
AB  - OBJECTIVES: Investigating the current, intended and potential reach of two
      effective smoking prevention programs in Dutch vocational schools and identifying
      determinants of school directors' intention to adopt these programs. STUDY
      DESIGN: Cross-sectional survey. METHODS: Two questionnaires were developed based
      on the Diffusion of Innovation theory and the I-Change model, focussing on either
      the 'Healthy School and Stimulants program' (HSS program) or the 'Out-of-school
      Computer Tailoring program' (CT program). The questionnaires were distributed
      amongst all Dutch vocational school directors (n = 452) of which 34% completed
      the questionnaire. RESULTS: The potential reach of the HSS program was 29%
      whereas the potential reach of the CT program was 5%. Regression analyses
      revealed that being female, perceiving a higher percentage of smoking students in
      school, having a personality more open towards change, perceiving a low need for
      a smoking prevention program, fewer disadvantages of the program, a higher level
      of self-efficacy towards adopting the program and a more positive social norm
      towards adopting a smoking prevention program from other school directors
      resulted in a positive intention towards adopting either program. CONCLUSIONS:
      The present study showed that the reach of effective smoking prevention programs
      is fairly low. School-based smoking prevention efforts are likely to improve if
      schools choose to use programs that are proven to be effective, which can be
      encouraged by adapting existing and newly designed programs to school directors'
      characteristics and providing easy access to reliable information regarding
      available programs.

PMID- 22365061
TI  - Dynamic annuloplasty for mitral regurgitation.
AB  - OBJECTIVE: The MiCardia DYANA annuloplasty system (MiCardia Corp, Irvine, Calif)
      is a nitinol-based dynamic complete ring that allows modification of the septal
      lateral diameter under transesophageal echocardiography guidance in the loaded
      beating heart after mitral valve repair. Shape alteration is induced by
      radiofrequency via detachable activation wires. This multicenter study reports
      the first human experience with this device. METHODS: Patients (n = 35, 67 +/- 8
      years) with degenerative (n = 29), functional/ischemic (n = 5), or rheumatic (n =
      1) mitral regurgitation underwent mitral valve repair using the new device. We
      analyzed the occurrence of death, endocarditis, ring dehiscence, systolic
      anterior motion, thromboembolism, pulmonary edema, heart block, ventricular
      arrhythmia, hemolysis, or myocardial infarction at 30 days (primary end point)
      and 6 months (secondary end point) postprocedure. RESULTS: All patients exhibited
      mitral regurgitation of 2 or less early postoperatively and at 6 months follow
      up. In 29 patients, the initial mitral valve repair result was satisfactory and
      no ring activation was required. In 6 patients, the nitinol-based ring was
      deformed intraoperatively postrepair with further improvement of mitral
      regurgitation in all cases (preactivation: 0.9 +/- 0.2, postactivation: 0.2 +/-
      0.3; P = .001). One death (2.9%, multisystem organ failure, non-device related),
      2 ventricular arrhythmias (5.7%), and 1 heart block (2.9%) occurred, all in the
      first 30 days after surgery. No additional major adverse clinical events occurred
      later than 1 month postprocedure (total observed major adverse clinical event
      rate 11.5%). CONCLUSIONS: The implantation of the new dynamic annuloplasty ring
      allows for safe mitral valve repair. The option of postrepair modification of the
      septal-lateral diameter by radiofrequency may further optimize repair results.

PMID- 22365062
TI  - Improving and standardizing capture of pediatric cardiac surgical complications.
AB  - OBJECTIVE: Our objective was to establish baseline data and develop a tool to
      allow for systematic evaluation of pediatric cardiac surgical complications. As a
      first step, we examined the incidence and distribution of complications, risk
      stratified by case complexity in a single institution. With improving mortality
      rates for congenital heart surgery, the next frontier for improving patient
      outcomes is characterizing and reducing complications. Currently, no standardized
      approach is available to monitor the incidence and severity of all complications
      associated with a congenital cardiac surgery program. METHODS: Complications
      occurring in pediatric cardiac surgical patients (January 2006 to March 2009)
      were collected by database review applying standardized definitions. The surgical
      procedures were stratified by complexity to analyze the distribution of
      complications over the risk spectrum. Each complication was assigned a severity
      coefficient (1-3) used to calculate the combined effect of frequency and
      severity. The cumulative sum method was used to determined the trend of the
      adverse outcomes. RESULTS: Of 292 procedures, 84 (28.8%) were associated with a
      total of 150 complications. Of the 150 complications, 37 occurred in patients who
      died. The most common complications were arrhythmias (14.5%), cardiac (12.6%),
      and operative (12.6%). There was a linear relationship between the frequency and
      severity of complications and surgical complexity, as stratified using the Risk
      Adjustment for Congenital Heart Surgery category or Aristotle basic complexity
      levels (Spearman's coefficient = 1). CONCLUSIONS: When examined in a systematic
      fashion, the risk of complications in pediatric cardiac surgical patients is
      considerable. Our data illustrate that it is possible to track complications over
      time in a consistent manner. The effect of complication monitoring on patient
      outcomes remains to be proved.

PMID- 22365063
TI  - Quality of life and survival of septuagenarians and octogenarians after repair of
      descending and thoracoabdominal aortic aneurysms.
AB  - OBJECTIVE: We assessed quality of life and survival in elderly patients after
      complex aortic operations to aid in surgical decision making. METHODS: A
      retrospective review was performed of 93 patients who underwent descending
      thoracic aneurysm or thoracoabdominal aortic aneurysm (TAAA) repair from 2002 to
      2008. A Cox model was used for survival analysis. The SF-36 Item Health Survey
      was administered to assess postoperative quality of life in 39 patients and was
      compared with age- and gender-matched normal scores. RESULTS: The mean age at
      operation was 75 +/- 4.1 years; 51% of patients were male. In-hospital mortality
      was 15%. One-year survival was 69%, and 5-year survival was 45%. Only acute
      respiratory distress syndrome was a predictor of in-hospital mortality (hazard
      ratio = 3.75; P < .01) and 1-year mortality (hazard ratio = 4.61; P < .001).
      After 1 year, patients enjoyed longevity equivalent to that of a normal age- and
      gender-matched population (standardized mortality ratio = 1.06; P = .81). Being
      male is a predictor of long-term survival (hazard ratio = 0.18; P < .05). For
      women, extremely low and high body mass indexes (quadratic term = 0.020; P < .05)
      with an inflection point of body mass index of 28 is a risk factor of long-term
      survival. Quality of life scores were similar to those of the general population
      except for lower vitality scores, (s-score = -0.67, 95% CI, -1.09 to -0.26).
      CONCLUSIONS: TAAA repair in this selected older surgical population yields
      acceptable survival beyond the first year. Among 1-year survivors, quality of
      life is similar to that of an age- and gender-matched population.

PMID- 22365064
TI  - Benefits of ambulatory axillary intra-aortic balloon pump for circulatory support
      as bridge to heart transplant.
AB  - OBJECTIVE: Axillary intra-aortic balloon pump therapy has been described as a
      bridge to transplant. Advantages over femoral intra-aortic balloon pump therapy
      include reduced incidence of infection and enhanced patient mobility. We
      identified the patients who would benefit most from this therapy while awaiting
      heart transplantation. METHODS: We conducted a single-center, retrospective
      observational study to evaluate outcomes from axillary intra-aortic balloon pump
      therapy. These included hemodynamic parameters, duration of support, and success
      in bridging to transplant. We selected patients on the basis of history of
      sternotomy, elevated panel-reactive antibody, and small body habitus. Patients
      were made to ambulate aggressively beginning on postoperative day 1. RESULTS:
      Between September 2007 and September 2010, 18 patients underwent axillary intra
      aortic balloon pump therapy. All patients had the devices placed through the left
      axillary artery with a Hemashield side graft (Boston Scientific, Natick, Mass).
      Before axillary placement, patients underwent femoral placement to demonstrate
      hemodynamic benefit. Duration of support ranged from 5 to 63 days (median = 19
      days). There was marked improvement in ambulatory potential and hemodynamic
      parameters, with minimal blood transfusion requirements. There were no device
      related infections. Some 72% of the patients (13/18) were successfully bridged to
      transplantation. CONCLUSIONS: Axillary intra-aortic balloon pump therapy provides
      excellent support for selected patients as a bridge to transplant. The majority
      of the patients were successfully bridged to transplant and discharged. Although
      this therapy has been described in previous studies, this is the largest series
      to incorporate a regimen of aggressive ambulation with daily measurements of
      distances walked.

PMID- 22365065
TI  - Aortic root numeric model: annulus diameter prediction of effective height and
      coaptation in post-aortic valve repair.
AB  - OBJECTIVE: The aim of the present study was to determine the influence of the
      aortic annulus (AA) diameter in order to examine the performance metrics, such as
      maximum principal stress, strain energy density, coaptation area, and effective
      height in the aortic valve. METHODS: Six cases of aortic roots with an AA
      diameter of 20 and 30 mm were numerically modeled. The coaptation height and area
      were calculated from 3-dimensional fluid structure interaction models of the
      aortic valve and root. The structural model included flexible cusps in a
      compliant aortic root with material properties similar to the physiologic values.
      The fluid dynamics model included blood hemodynamics under physiologic diastolic
      pressures of the left ventricle and ascending aorta. Furthermore, zero flow was
      assumed for effective height calculations, similar to clinical measurements. In
      these no-flow models, the cusps were loaded with a transvalvular pressure
      decrease. All other parameters were identical to the fluid structure interaction
      models. RESULTS: The aortic valve models with an AA diameter range of 20 to 26 mm
      were fully closed, and those with an AA diameter range of 28 to 30 mm were only
      partially closed. Increasing the AA diameter from 20 to 30 mm decreased the
      averaged coaptation height and normalized cusp coaptation area from 3.3 to 0.3 mm
      and from 27% to 2.8%, respectively. Increasing the AA diameter from 20 to 30 mm
      decreased the effective height from 10.9 to 8.0 mm. CONCLUSIONS: A decreased AA
      diameter increased the coaptation height and area, thereby improving the
      effective height during procedures, which could lead to increased coaptation and
      better valve performance.

PMID- 22365066
TI  - Topical anesthesia versus regional anesthesia for cataract surgery: a meta
      analysis of randomized controlled trials.
AB  - PURPOSE: To examine possible differences in the clinical outcomes of topical
      anesthesia (TA) and regional anesthesia including retrobulbar anesthesia (RBA)
      and peribulbar anesthesia (PBA) in phacoemulsification. DESIGN: Systematic review
      and meta-analysis. PARTICIPANTS: Patients from previously published randomized
      controlled trials (RCTs) of phacoemulsification under TA and RBA/PBA reporting
      clinical outcomes. METHODS: A comprehensive literature search was performed
      according to the Cochrane Collaboration method to identify RCTs that compare TA
      and RBA/PBA in phacoemulsification. MAIN OUTCOME MEASURES: Primary outcome
      parameters investigated were pain score during and after surgery, intraoperative
      difficulties and inadvertent ocular movement, intraoperative necessity to
      administer additional anesthesia, and patient preference. Secondary outcome
      parameters investigated were postoperative visual acuity, anesthesia-related
      complications, intraoperative complications, and severe local or systemic
      complications. RESULTS: Fifteen studies were identified and analyzed to compare
      TA (1084 eyes) with RBA/PBA (1121 eyes) in phacoemulsification. Data synthesis
      showed that intraoperative and postoperative pain perception was significantly
      higher in the TA group (P < 0.05). The TA group showed more frequent inadvertent
      ocular movement (P < 0.05) and a greater intraoperative need for supplementary
      anesthesia (P = 0.03). There was no statistically significant difference between
      the 2 groups in intraoperative difficulties as assessed by the surgeons (P >
      0.05). Patients significantly preferred TA (P < 0.00001). The RBA/PBA group had
      more frequent anesthesia-related complications, such as chemosis, periorbital
      hematoma, and subconjunctival hemorrhage (P < 0.05). There was no statistically
      significant difference in surgery-related complications (P > 0.05). CONCLUSIONS:
      Compared with RBA/PBA, TA does not provide the same excellent pain relief in
      cataract surgery; however, it achieves similar surgical outcomes. Topical
      anesthesia reduces injection-related complications and alleviates patients' fear
      of injection. The choice of TA is not suitable for patients with a higher initial
      blood pressure or greater pain perception.

PMID- 22365067
TI  - Characteristics of an Acanthamoeba keratitis outbreak in British Columbia between
      2003 and 2007.
AB  - OBJECTIVE: Quantify and describe Acanthamoeba keratitis (AK) cases in British
      Columbia (BC). DESIGN: A comparison of annual incidence rates confirms the
      presence of an outbreak. A case series describes characteristics of the outbreak.
      PARTICIPANTS: All laboratory-confirmed AK cases (persons) in BC (1988-2011; n =
      68) were included in the incidence rate comparison. Of the 42 cases (persons)
      between 2003 and 2007, 32 were selected to interview (laboratory confirmed, 2005
      2007), and the 23 who completed interviews form the case series. METHODS: A
      comparison of standardized annual incidence rates in historic to outbreak periods
      is performed by z-score test. A telephone interview and descriptive analysis
      detailing demographics, risk factors, and contact lens (CL) wearing habits was
      completed for 23 cases. MAIN OUTCOME MEASURES: We measure number of laboratory
      confirmed cases in BC. In addition, risk factors and potential exposures of these
      cases are reported. RESULTS: The annual incidence of AK increased significantly
      from 0.029 to 0.200 per 100 000 population between historic years (1988-2002) and
      outbreak years (2003-2007; P = 0.022). The annual incidence of AK has since
      returned to near historic levels (0.056/100 000 population). The case series
      identified multiple risk factors, including the use of a specific recalled
      solution (60.9%), daily soft CL wear (95.7%), all-in-one solutions (95.7%),
      showering while wearing CL (65.2%), and generally poor CL hygiene. CONCLUSIONS: A
      significant increase in annual AK incidence occurred between 2003 and 2007 in BC.
      After 2007, the incidence of AK returned to near historic levels. The recalled
      solution was associated with many cases; however, other risk factors were also
      identified, including being unaware of the recall and poor CL hygiene practices,
      highlighting the need for improved education about the severity of AK and
      consequences of improper CL hygiene. FINANCIAL DISCLOSURE(S): The authors have no
      proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 22365068
TI  - Protein folding in membranes.

PMID- 22365069
TI  - Serum zinc levels and goiter in Iranian school children.
AB  - Iodine deficiency has been shown to have high prevalence in Iran despite
      sufficient iodine supplementation. Zinc deficiency may also contribute to the
      pathogenesis of endemic goiter. The aim of this study was to compare serum zinc
      level in Iranian school children with and without goiter. A cross-sectional study
      was performed among urban children aged 8-12 years in city of Kerman, Iran. A
      multistage proportional to size cluster sampling method was used to screen 5500
      subjects out of 29,787 students. After the screening phase, serum and urine
      specimens of randomly selected 165 students were evaluated for serum zinc levels
      and urinary iodine excretion and compared in goiterous and non-goiterous
      children. Serum zinc level was 149.5+/-29.4 MUg/l in goiterous children and
      141.2+/-52 MUg/l in non-goiterous children but no significant difference was
      found between the groups (p=0.37). But urinary iodine excretion was significantly
      (p<0.001) lower in goiterous children (207.5 MUg/l in goiterous children and
      262.5 MUg/l in non-goiterous children). This study showed that serum zinc level
      in goiterous and non-goiterus children is not different and zinc deficiency is
      not a risk factor for endemic goiter in this population.

PMID- 22365070
TI  - Low serum zinc levels in patients undergoing coronary angiography correlate with
      immune activation and inflammation.
AB  - INTRODUCTION: Low serum zinc concentrations are associated with adverse outcomes.
      To explain this phenomenon we aimed to investigate whether low zinc levels are
      related to immune activation, renal function and coronary artery disease (CAD).
      METHODS: Serum concentrations of zinc and the immune activation markers neopterin
      and C-reactive protein (CRP) were measured in 2048 patients derived from the
      LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among
      patients referred for coronary angiography. RESULTS: Zinc concentrations did not
      differ between patients with CAD (mean+/-SD: 13.3+/-2.4 MUmol/L) and controls
      (13.3+/-2.2 MUmol/L; Welch's t test: p=n.s.) but CAD patients had higher
      neopterin (8.6+/-7.4 nmol/L) and CRP (9.7+/-19.6 mg/L) concentrations compared to
      controls (neopterin: 7.5+/-4.8 nmol/L, p=0.0005; CRP: 5.5+/-10.0 mg/L, p<0.0001).
      There was an inverse correlation between serum zinc concentrations and neopterin
      (Spearman's rank correlation: r(s)=-0.222) and CRP (r(s)=-0.166; both p<0.0001)
      concentrations. CONCLUSIONS: Our results indicate increased inflammatory
      processes in patients with low zinc levels. Further studies should clarify
      whether inflammation related processes such as renal wasting contribute to zinc
      deficiency and underlie the adverse health consequences of low serum zinc levels.

PMID- 22365071
TI  - Concentrations of trace elements in bones of the hip joint from patients after
      hip replacement surgery.
AB  - The aim of this research was to determine the concentrations of two essential
      elements (copper (Cu) and zinc (Zn)) and three toxic elements (lead (Pb), cadmium
      (Cd) and mercury (Hg)) in the hip joint bones of patients from the Chair and
      Clinic of Orthopaedics and Traumatology at the Pomeranian Medical University in
      Szczecin. We examined 111 samples of hip joint bones obtained from patients from
      north-western Poland who had undergone arthroplasty of the femoral head. In
      cartilage with the adjacent compact bone, and in spongy bone from the examined
      patients, the concentrations (medians) determined were placed in the following
      descending sequence Zn>Pb>Cu>Cd>Hg. The concentrations ranged from 86 mg Zn/kg to
      0.0020 mg Hg/kg dw. It was found that the concentration of lead in the cartilage
      with adjacent compact bone was higher in men than in women. In conclusion, it
      seems that in addition to routine monitoring of the abiotic environment, it is
      essential to monitor concentrations of heavy metals having a long-term impact in
      humans.

PMID- 22365072
TI  - Selenium levels in men with liver disease in Hungary.
AB  - PROJECT: We studied the relationship between selenium (Se) levels and chronic
      liver disease (CLD) severity and the association between socioeconomic and
      lifestyle factors and serum Se levels. PROCEDURE: We performed a case-control
      study in Hungarian men, examining 281 patients with CLD and 778 controls. Liver
      function was evaluated using biochemical markers, and liver disease was verified
      with physical examination and blood tests. Linear regression analysis was
      performed to study the association of serum Se level with biochemical markers in
      cases and controls. In control participants we examined the relationship between
      Se levels and age, financial status, education, alcohol consumption, cigarette
      smoking, type of fat used for cooking and body mass index. RESULTS: Serum Se
      levels were lower in cases (median 0.87 MUmol/L (IQR: 0.77-1.03)) than in
      controls (median 1.08 MUmol/L (IQR: 0.97-1.19)). In controls, increases in
      bilirubin and glutamic-oxaloacetic transaminase (GOT) were associated with
      decreases in Se levels. In patients with CLD, a statistically significant
      relationship was found between serum Se and the GOT/GPT ratio, albumin and
      bilirubin. Younger, better-educated controls had significantly higher, and
      regular smokers and heavy drinkers had significantly lower Se levels. The use of
      vegetable oil/fat was also associated with higher Se levels. Se level was
      associated with the severity of liver injury in people even in patients who did
      not exhibit signs and symptoms of CLD. CONCLUSIONS: Serum Se level is strongly
      associated with the severity of liver damage in people with CLD from the early
      stage on.

PMID- 22365073
TI  - Kinetics of zinc status and zinc deficiency in Berardinelli-Seip syndrome.
AB  - Berardinelli-Seip syndrome (BSS) is a very rare disorder characterized by near
      complete absence of adipose tissue from birth or early infancy, hypoleptinemia,
      hypertriglyceridemia, insulin resistance, diabetes mellitus, and other clinical
      signals. It is caused by mutations in AGPAT2 or Gng3lg. We evaluated 10 BSS
      patients and 10 healthy subjects. A single dose of 382.43 MUmol zinc was
      administered intravenously before and after 3 months of oral zinc
      supplementation. Blood samples were collected from the contralateral arm at 0,
      30, 60, 90, and 120 min after zinc injection. Plasma and serum were obtained to
      measure hematological and biochemical parameters. Urine was collected to measure
      creatinine, protein, and zinc. Basal serum zinc levels were similar in controls
      and BSS patients. However, serum zinc profiles were significant reduced in BSS
      patients in comparison with controls. The change in total-body zinc clearance was
      more significant in BSS patients, indicating that these patients had suboptimum
      zinc deficiency.

PMID- 22365074
TI  - Copper deprivation modulates CTR1 and CUP1 expression and enhances cisplatin
      cytotoxicity in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae has been established as a model system for cancer
      studies, due to the widely conserved family of genes involved in cell cycle
      progression, proliferation and apoptosis. In the current study, we sought to
      determine whether copper deprivation modulates sensitivity of yeast to cisplatin.
      Yeast cultures grown in low copper medium and exposed to bathocuproiene disulfate
      (BCS) resulted in significant reduction of intracellular copper. We report here
      that low copper medium rendered BY4741 hypersensitive to cisplatin (CDDP). Yeast
      grown in low copper medium exhibited ~2.0 fold enhanced cytotoxicity in survival
      and colony-forming ability, compared to copper adequate control cells grown in
      YPD. The effect of copper restriction on CDDP sensitivity appeared to be
      associated with the up regulation of CTR1, facilitating enhanced uptake and
      accumulation of CDDP. Also, CDDP further lowered copper deprivation-induced
      changes in CUP1 metallothionein levels, SOD activity and GSH levels. These
      changes were associated with increased protein oxidation and lipid peroxidation
      induced by CDDP. These results thus suggest that cisplatin cytotoxicity is
      potentiated under low copper conditions due to enhanced uptake and accumulation
      of cisplatin and also in part due to lowered antioxidant defense and increased
      oxidative stress imposed by copper deprivation.

PMID- 22365076
TI  - Increased expression of macrophage colony-stimulating factor and its receptor in
      patients with endometriosis.
AB  - OBJECTIVE: To investigate the expression and regulation of colony-stimulating
      factor 1 (CSF-1) and its receptor, C-FMS, in endometriosis. DESIGN: In vivo and
      vitro study. SETTING: University-based academic medical center. PATIENT(S):
      Reproductive-age women undergoing surgery for benign conditions. INTERVENTION(S):
      Peritoneal and endometrial tissue samples were obtained. MAIN OUTCOME MEASURE(S):
      CSF-1 and C-FMS expression. RESULT(S): Significantly higher CSF-1 levels were
      found in peritoneal fluid of patients with endometriosis compared with control
      subjects. Ectopic endometriotic tissue had 3.5-fold and 1.7-fold increases in CSF
      1 and C-FMS expression, respectively, compared with eutopic tissue. Coculture of
      endometrial cells from either established cell lines or patient samples with
      peritoneal mesothelial cells (PMCs) led to increased expression of CSF-1 and C
      FMS. A higher but nonsignificant increase in levels of C-FMS and CSF-1 was found
      in cocultures of endometrial epithelial cells from patients with endometriosis
      compared with those without endometriosis. CONCLUSION(S): Increased CSF-1 levels
      may contribute to endometriosis lesion formation and progression. Elevation in
      CSF-1 after coculture of endometrial cells with PMCs suggests that endometrial
      tissue may be a source of peritoneal CSF-1. Increased C-FMS expression in
      endometrial cells from women with endometriosis cocultured with PMCs suggests
      that endometrial tissue involved in lesion formation is highly responsive to CSF
      1 signaling.

PMID- 22365075
TI  - The use of recombinant luteinizing hormone in patients undergoing assisted
      reproductive techniques with advanced reproductive age: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of recombinant LH in assisted reproduction
      technology (ART) cycles in patients of advanced reproductive age. DESIGN: A
      systematic review and meta-analysis. SETTING: Published randomized controlled
      clinical trials comparing recombinant LH plus recombinant FSH versus recombinant
      FSH only in patients of advanced reproductive age. PATIENT(S): Patients 35 years
      and older undergoing assisted reproduction. INTERVENTION(S): Recombinant LH plus
      recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH
      stimulation only in assisted reproduction cycles. MAIN OUTCOME MEASURE(S):
      Implantation and clinical pregnancy. RESULT(S): Seven trials were identified that
      met inclusion criteria and comprised 902 assisted reproduction technology cycles.
      No differences in serum E(2) on the day of hCG administration were reported in
      any trials. Two trials reported lower oocyte yield and one trial reported lower
      metaphase II oocyte yield in the recombinant LH-supplemented group. One trial
      reported higher fertilization rates in the recombinant LH-supplemented group. In
      a fixed effect model, implantation was higher in the recombinant LH-supplemented
      group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical
      pregnancy was increased in the recombinant LH-supplemented group (odds ratio
      1.37, 95% confidence interval 1.03-1.83). CONCLUSION(S): The addition of
      recombinant LH to ART cycles may improve implantation and clinical pregnancy in
      patients of advanced reproductive age.

PMID- 22365077
TI  - Electroejaculation combined with intracytoplasmic sperm injection in patients
      with psychogenic anejaculation yields comparable results to patients with spinal
      cord injuries.
AB  - OBJECTIVE: To evaluate sperm quality and fertility potential of men with
      psychogenic anejaculation treated by electroejaculation (EEJ) and
      intracytoplasmic sperm injection (ICSI). Treatment results were compared to
      spinal cord injured (SCI) patients treated similarly. DESIGN: Retrospective
      clinical study. SETTING: Academic tertiary referral fertility center. PATIENT(S):
      Couples with isolated psychogenic anejaculation or SCI. INTERVENTION(S):
      Electroejaculation and ICSI. MAIN OUTCOME MEASURE(S): Semen analysis,
      fertilization rate, implantation rate, pregnancy rate, delivery rate and safety
      of the procedure. RESULT(S): Fifteen patients diagnosed with psychogenic
      anejaculation underwent 40 EEJ/ICSI cycles. The semen retrieved was characterized
      by low motility (mean 10.7% +/- 12.3%), normal volume (2.2 +/- 1.9 mL) and normal
      count (25.1 +/- 29.9 * 10(6)/mL), according to World Health Organization
      criteria. Results of EEJ/ICSI were compared with 22 SCI patients treated by 66
      EEJ/ICSI cycles during the same period. Mean female age and the number of oocytes
      retrieved per cycle were similar between the groups. Similar semen parameters
      after EEJ were found between psychogenic and SCI patients. Fertilization rate was
      significantly lower in the psychogenic patients compared to SCI (47.0% and 57.0%,
      respectively). No significant differences were found regarding pregnancy rates
      (20% and 22.7%, respectively), implantation rate (10.2% and 11.6%, respectively)
      or delivery rates (15% and 18.2%, respectively). CONCLUSION(S): Sperm retrieved
      by EEJ is characterized by asthenospermia and normal count. In spite of the lower
      fertilization rate in psychogenic patients, combination of EEJ and ICSI gives
      adequate results to couples with psychogenic anejaculation similar to the results
      obtained for SCI patients. Current results give these couples a reasonable chance
      of pregnancy achievement.

PMID- 22365078
TI  - [Impact of overactive bladder treatment on associated comorbidities].
AB  - OBJECTIVES: To analyze the management of patients newly diagnosed with overactive
      bladder (OAB) and to assess the impact of treatment on associated comorbidities.
      MATERIAL AND METHODS: 1,434 patients over 60 years with newly diagnosed OAB and
      at least one associated comorbidity (urinary tract infections, genital skin
      infections, sleep disturbances, depression, and hypertension) were recruited in
      300 urology/gynecology surgeries in Spain. In the first visit sociodemographic
      and clinic data were recorded, and treatment for OAB following usual practice was
      prescribed. 4-6 months later symptoms were reevaluated. A descriptive statistical
      analysis was performed, variables were compared by gender (Chi(2)/Mann-Whitney)
      and between visits (McNemar). RESULTS: Data for 1,274 valid patients in visit 1
      and 1,153 in visit 2 are presented. Mean age in the sample was 68.17(6.19) years,
      71.51% were women. 66.41% presented urgency, with or without urge urinary
      incontinence, and 33.59% presented urgency related to stress urinary
      incontinence. The most frequent associated pathologies were sleep disturbances
      (56.44%) and urinary tract infections (53.14%). Urinary tract infections and
      genital skin infections and treatment for depression were more frequent in women;
      sleep disturbances and hypertension in men. Treatments more frequently prescribed
      were anticholinergics (95.45%) and guidance for lifestyle changes (85.32%).
      Statistically significant improvement in symptoms of associated comorbidities was
      detected in visit 2. CONCLUSIONS: Detection and treatment of OAB symptoms is
      relevant to reduce both the impact of the affection and of associated
      pathologies.

PMID- 22365079
TI  - [Endovascular treatment of stenosis of the renal artery in transplanted kidney].
AB  - INTRODUCTION: The incidence of renal artery stenosis in the transplanted kidney
      (TRAS) varies between 2 and 23%, being the most frequent vascular complication
      following renal trasplantation. The delay in diagnosis and treatment can lead to
      functional graft loss. Percutaneous trasluminal angioplasty with stent (PTAS) is
      the treatment of choice to restore kidney perfusion. MATERIALS AND METHODS:
      Retrospective review of renal transplant casuistic in our institution between
      September 2005 and August 2009. Were included patients with greater than 70% TRAS
      and impaired graft function, treated with PTAS. Follow-up at 3, 12 and 36 months
      was done with creatinine, glomerular filtration rate (GFR) and Doppler
      ultrasonography (DUS). Technical success was defined as correct stent placement
      associated with decreased flow, and clinical success as improve renal function
      during follow-up. RESULTS: Incidence of TRAS was 7.3% (22/298), 60% PTAS
      subsidiary. 100% technical success and 84.6% clinical success, 15.4% without
      changes in renal function. 84% decreases flow rate greater than 70% by DUS, and
      26% up to 60%. Wave changes from type III to type II were recorded in 69% and to
      type I in 33%. CONCLUSIONS: The PTAS is a safe and effective procedure for the
      treatment of selected TRAS patients, as it preserves vascular permeability in
      short and medium term, ensuring the functionality of the graft. DUS is the method
      of choice for diagnosis and monitoring TRAS.

PMID- 22365080
TI  - [Update on the diagnosis and treatment of vulvodynia].
AB  - CONTEXT: Vulvodynia is a complex and multifactorial clinical condition. It is
      defined as chronic vulvar discomfort characterized by burning, stinging or
      irritation. Its diagnostic difficulty and treatment is known. OBJECTIVES: To
      review the medical literature of the last 10 years from a critical point of view.
      EVIDENCE ACQUISITION: A search was made in Medline/Pubmed and the Cochrane
      Library using the terms vulvodynia and vestibulodynia to which etiology,
      epidemiology, diagnosis, neurophysiological test and treatment or management,
      were added. EVIDENCE SYNTHESIS: In spite of the advances achieved in all of the
      aspects of vulvodynia, the methodology used at present in many cases does not
      have the desirable statistical soundness: there are few control or placebo
      controlled groups and double-blind studies. Uniformity is lacking in the scales,
      indexes and questionnaires for the correct evaluation of pain before and after
      the treatment and debatable diagnostic criteria are use. The limited use of
      neurophysiological diagnostic resources that validate the clinical findings has
      been observed in the studies analyzed. In most of the works, the medical
      treatments have been shown to be ineffective. Physiotherapy and cognitive
      behavioral therapy seem to be promising therapeutic tools. Surgery
      (vestibulectomy) stands out by its demonstrated efficacy in the publications
      studied. CONCLUSIONS: A multidisciplinary approach is always necessary. Topical
      medical, psychological and physical therapy treatments may have sum effects and
      become an alternative to surgery. New pathways of research and more regulated
      studies are required.

PMID- 22365081
TI  - [Relevance of the clinical-pathological predictive factors in force in
      chromophobe renal cell cancer].
AB  - INTRODUCTION: The identification of new subtypes of renal cell carcinoma (RCC)
      has made it necessary to re-evaluate the current clinical and pathological
      predictive factors (stage, Fuhrman nuclear grade, necrosis, lymphovascular
      invasion [LVI] and sarcomatoid component) in these new subtypes. The chromophobe
      renal cell carcinoma (CRCC) is considered a less aggressive subtype of RCC. The
      purpose of this article is to evaluate the usefulness of current
      clinicopathologic predictors of RCC in our series of CRCC. MATERIAL AND METHODS:
      We retrospectively reviewed the clinicopathologic features of 63 patients with
      CRCC treated with radical nephrectomy. The parameters analyzed were tumor
      extension with the TNM, grade according to Fuhrman classification, LVI, tumor
      necrosis, tumor thrombus, surgical margin status, and involvement of the
      collecting system. The results (disease recurrence) were evaluated by Cox
      regression model with univariate and multivariate analysis. RESULTS: With a
      median follow up of 60.2 months (0.37-160.2), 8 (11%) patients had recurrence,
      with median time to recurrence of 31.7 months (5.37-124.33). In the univariate
      analysis, TNM extension (p=0.0001), Fuhrman grade III or IV (p=0.031), LVI
      (p=0.0001) and the presence of positive surgical margins (p=0.0001) were
      statistically significant variables for recurrence. In the multivariate analysis,
      only tumor stage was confirmed as an independent predictor of recurrence, pT1
      versus pT2 (p=0.02, OR 0.27 95% CI 0.03-0.258) and pT2 versus higher stage
      (p=0.037, OR 0.173 95% CI 0.033-0.896). CONCLUSIONS: The tumor stage predicts
      aggressiveness in the CCRC. The classification of Fuhrman nuclear grade is not
      useful for this histological subtype.

PMID- 22365082
TI  - [Effects of delivery and oophorectomy on urethral collagen: an experimental
      study].
AB  - OBJECTIVE: Stereological evaluation of the concentration of type I and III
      collagen fibers in the urethral tissue of rats subjected to simulated labor and
      oophorectomy. To compare the concentrations of collagen between oophorectomized
      and non-oophorectomized rats. MATERIAL AND METHOD: Sixty adult Wistar rats were
      divided into six groups. A group made up of virgin rats was used as control group
      and another group was made up of oophorectomized rats. Two groups underwent
      vaginal distention for 30 and 120 minutes, respectively. The two other groups
      were subjected to the same distension periods, followed by oophorectomy. Sixty
      days later, euthanasia and removal of urethral tissue was carried out for
      stereological analysis of type I and III collagen after staining with hematoxylin
      and eosin and picrosirius red. RESULTS: A decrease in estrogen levels was
      observed in the oophorectomized rats. There was a reduction of type III collagen
      in the oophorectomized control group compared to the control group when analyzed
      independently. No significant differences were observed among the other groups.
      Type I collagen decreased in all groups compared to the control group. However,
      in the prolonged vaginal distension and oophorectomy group, these fibers
      increased. CONCLUSION: In normal rats, simulation of labor does not alter the
      collagen III levels. In hypoestrogenic rats, the concentration of collagen type I
      and III decreased, except in those undergoing prolonged labor simulation in which
      collagen I increased.

PMID- 22365084
TI  - Visual performance after posterior chamber phakic intraocular lens implantation
      and wavefront-guided laser in situ keratomileusis for low to moderate myopia.
AB  - PURPOSE: To compare postoperative visual function after implantable collamer lens
      (ICL) implantation and after wavefront-guided laser in situ keratomileusis
      (LASIK) in eyes with low to moderate myopia. DESIGN: Retrospective observational
      case study. PATIENTS AND METHODS: We investigated 30 eyes of 20 patients
      undergoing ICL implantation and 64 eyes of 38 patients undergoing wavefront
      guided LASIK for the correction of low to moderate myopia (manifest spherical
      equivalent: -3.00 to -5.88 diopters [D]). Ocular higher-order aberrations (HOAs)
      and contrast sensitivity (CS) function were measured by Hartmann-Shack
      aberrometry and a contrast sensitivity unit before and 3 months after surgery,
      respectively. From the contrast sensitivity, the area under the log contrast
      sensitivity function was calculated. RESULTS: For 4-mm and 6-mm pupils, the
      changes in ocular third-order aberrations, fourth-order aberrations, and total
      HOAs after ICL implantation were significantly less than those after wavefront
      guided LASIK (P < .05, Mann-Whitney U test). The postoperative area under the log
      contrast sensitivity function was significantly increased after ICL implantation
      (P < .001), whereas, after wavefront-guided LASIK, it was not significantly
      changed (P = .11). CONCLUSIONS: ICL implantation induces significantly fewer
      ocular HOAs than wavefront-guided LASIK. Moreover, CS was significantly improved
      after ICL implantation but unchanged after wavefront-guided LASIK in eyes with
      low to moderate myopia. Thus, even in the correction of low to moderate myopia,
      ICL implantation appears to be superior in visual performance to wavefront-guided
      LASIK, suggesting that it may be a viable surgical option for the treatment of
      such eyes.

PMID- 22365083
TI  - Interleukin-10 plays a crucial role in suppression of experimental autoimmune
      encephalomyelitis by Bowman-Birk inhibitor.
AB  - The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor
      with anti-inflammatory properties. Experimental autoimmune encephalomyelitis
      (EAE) serves as an animal model of the central nervous system (CNS) inflammatory
      disorder multiple sclerosis (MS). EAE is mediated by Th1 and Th17 cells which
      migrate into the CNS and initiate inflammation directed against myelin
      components, resulting in CNS pathology and neurological clinical deficit. We have
      shown previously that oral treatment with BBI delays onset of EAE and reduces its
      severity. These beneficial effects were associated with an increase in IL-10
      secretion by immune cells of BBI-treated mice. It is not known, however, whether
      this was a causal relationship or simply an epiphenomenon. In the present study
      we provide evidence that BBI regulates CD4+ T cell immune responses in EAE. BBI
      administration delayed the onset of EAE and reduced its severity in an IL-10
      dependent manner, as BBI-mediated suppression of EAE was abrogated in IL-10
      knockout mice. The beneficial effects were accompanied by reduced IFN-gamma, IL
      17 and increased IL-10 production, as well as increased Foxp3 expression. CD4+ T
      cells were the major source of IL-10 in the periphery and in the CNS during BBI
      treatment. Furthermore, BBI-treated mice had reduced numbers of infiltrated cells
      in the CNS, including Th17 cells, as compared with PBS-treated control animals.
      In conclusion, our data provide clear evidence for the essential role of IL-10 in
      BBI-mediated suppression in EAE, and indicate that BBI may be a promising
      candidate for the development of a novel MS therapy.

PMID- 22365085
TI  - The efficacy and tolerability of exenatide in comparison to placebo; a systematic
      review and meta-analysis of randomized clinical trials.
AB  - Recent investigations in finding new drugs in the treatment of diabetes have led
      to the discovery of several pathological pathways involved in diabetes. Exenatide
      a drug with incretin mimetic activity was studied in several in vivo and in vitro
      as well as human studies. It has shown promising results in controlling metabolic
      indices in type-2 diabetes and was approved by FDA but still there is an active
      safety alert on it. In this study we aimed to meta-analyze all placebo-controlled
      clinical trials on the efficacy or tolerability of exenatide in type 2 diabetes.
      The literature search provided 1016 articles while only 14 articles were eligible
      to be included in the meta-analysis with a total of 2583 patients enrolled in the
      study. According to the wide variation in design of various studies, the study
      duration of 16 weeks and less or more and dose (5 MUg bid versus 10 MUg bid) were
      considered and analyzed. The results of this meta-analysis show that exenatide
      decreases fasting plasma glucose and HbA1C significantly regardless of dose and
      study duration. The effect of exenatide on weight reduction was more prominent at
      the dose of 10 MUg bid regardless of the study duration, however at the dose of 5
      MUg bid, significant results were observed after drug administration for more
      than 16 weeks. Exenatide usage decreased serum triglycerides indifferent to dose
      and study duration while its effect on cholesterol was not prominent. Along with
      these impacts, exenatide changed LDL and HDL cholesterol at the lower dose. The
      hemodynamic effect of exenatide was observed as significant decrements in
      systolic and diastolic blood pressure at the higher dose. The risk of nausea,
      vomiting and hypoglycemia was significant and indifferent to dose while headache
      and nasopharyngaitis were seen more at lower dose. It is concluded that exenatide
      can be considered as a good hypoglycemic agent in type-2 diabetic patients with
      benefits on lipid profile and blood pressure with partially questionable
      tolerability.

PMID- 22365086
TI  - Multidrug resistance reversal effects of aminated thioxanthones and interaction
      with cytochrome P450 3A4.
AB  - PURPOSE: Aminated thioxanthones have recently been described as dual-acting
      agents: growth inhibitors of leukemia cell lines and P-glycoprotein (P-gp)
      inhibitors. To evaluate the selectivity profile of thioxanthones as inhibitors of
      multidrug resistance (MDR), their interaction with other ABC transporters, which
      were found to have a strong correlation with multidrug resistance, such as
      multidrug resistant proteins 1 (MRP1), 2 (MRP2) and 3 (MRP3) and breast cancer
      resistance protein (BCRP) was also evaluated. The interaction of thioxanthones
      with cytochrome P450 3A4 (CYP3A4) together with the prediction of their binding
      conformations and metabolism sites was also investigated. METHODS: The UIC2
      monoclonal antibody-labelling assay was performed using P-gp overexpressing
      leukemia cells, K562Dox, incubated with eight thioxanthonic derivatives, in order
      to confirm their P-gp inhibitory activity. A colorimetric-based ATPase assay
      using membrane vesicles from mammalian cells overexpressing a selected human ABC
      transporter protein (P-gp, MRP1, MRP2, MRP3, or BCRP) was performed. To verify if
      some of the thioxanthonic derivatives were substrates or inhibitors of CYP3A4, a
      luciferin-based luminescence assay was performed. Finally, the in silico
      prediction of the most probable metabolism sites and docking studies of
      thioxanthones on CYP3A4 binding site were investigated. RESULTS: Thioxanthones
      interacted not only with P-gp but also with MRP and BCRP transporters. These
      compounds also interfere with CYP3A4 activity in vitro, in accordance with the in
      silico prediction. CONCLUSION: Thioxanthonic derivatives are multi-target
      compounds. A better characterization of the interactions of these compounds with
      classical resistance mechanisms may possibly identify improved treatment
      applications.

PMID- 22365087
TI  - Effectiveness and safety of abatacept in moderate to severe rheumatoid arthritis.
AB  - PURPOSE: Abatacept was approved in our hospital by the Pharmacy and Therapeutics
      Committee for treatment of moderate to severe rheumatoid arthritis (RA) in adult
      patients with inadequate response or intolerance to disease modifying
      antirheumatic drugs (DMARDs), including at least one anti-tumour necrosis factor
      (anti-TNF). The objectives of this study were to analyze compliance with our
      protocol and to evaluate effectiveness and safety of abatacept in our patients.
      METHODS: We performed a descriptive longitudinal study of patients with RA
      treated with abatacept between August 2008 and May 2010 in our day care unit. We
      reviewed clinical records and recorded the following data: sex, age, weight, year
      of diagnosis, previous antirheumatic treatments and reasons for withdrawal of
      anti-TNFs, indication for abatacept, dose and date of administration, Disease
      Activity Score (DAS28) and adverse events. Effectiveness was evaluated using the
      European League Against Rheumatism (EULAR) criteria. RESULTS: We recruited 16
      patients. Mean follow-up time was 10.4 (SD: 6.1) months. All patients had been
      previously treated with DMARDs, including at least one anti-TNF, and the mean
      dose of abatacept was 9.4 (SD: 1.4) mg/kg. During the first 6 months of
      treatment, 11/16 of patients experienced a decrease in their DAS28 value, but
      only 5/16 achieved a satisfactory response. Dyspnea was the most frequent adverse
      event (7/16), followed by fatigue and asthenia (6/16) and dry skin (5/16).
      CONCLUSIONS: The indication for abatacept in our hospital complied with the
      protocol approved by the Pharmacy and Therapeutics Committee. Only 5/16 of
      patients achieved a satisfactory response; however, it should be noted that these
      patients had moderate to severe RA that was refractory to other treatments.
      Adverse reactions were consistent with those described in the summary of product
      characteristics. Further studies with larger cohorts are needed to analyze the
      long-term safety and effectiveness profile in clinical practice.

PMID- 22365088
TI  - Nonclassical biological activities of quinolone derivatives.
AB  - Quinolones are considered as a big family of multi-faceted drugs; their chemical
      synthesis is flexible and can be easily adapted to prepare new congeners with
      rationally devised structures. This is shown by the description of many thousands
      of derivatives in the literature. Scientists could accurately describe their
      QSAR, which is essential for effective drug design. This also gave them the
      chance to discover new and unprecedented activities, which makes quinolones an
      endless source of hope and enables further development of new clinically useful
      drugs. Quinolones are among the most common frameworks present in the bioactive
      molecules that have dominated the market for more than four decades. Since 1962,
      4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial
      agents. Quinolones have a broad and potent spectrum of activity and are also used
      as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been
      reported to display "nonclassical" biological activities, such as antitumor, anti
      HIV-1 integrase, anti-HCV-NS3 helicase and -NS5B-polymerase activities. The
      present review focuses on the structural modifications responsible for the
      transformation of an antibacterial into an anticancer agent and/or an antiviral
      agent. Indeed, quinolones' antimicrobial action is distinguishable among
      antibacterial agents, because they target different type II topoisomerase
      enzymes. Many derivatives of this family show high activity against bacterial
      topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured
      mammalian cells and in vivo tumor models. Moreover, quinolones have shown
      antiviral activity against HIV and HCV viruses. In this context the quinolones
      family of drugs seem to link three different biological activities
      (antibacterial, anticancer, and the antiviral profiles) and the review will also
      provide an insight into the different mechanisms responsible for these activities
      among different species.

PMID- 22365089
TI  - Sample sizes for designing bioequivalence studies for highly variable drugs.
AB  - PURPOSE: To provide tables of sample sizes which are required, by the European
      Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), for the
      design of bioequivalence (BE) studies involving highly variable drugs. To
      elucidate the complicated features of the relationship between sample size and
      within-subject variation. METHODS: 3- and 4-period studies were simulated with
      various sample sizes. They were evaluated, at various variations and various true
      ratios of the two geometric means (GMR), by the approaches of scaled average BE
      and by average BE with expanding limits. The sample sizes required for yielding
      80% and 90% statistical powers were determined. RESULTS: Because of the
      complicated regulatory expectations, the features of the required sample sizes
      are also complicated. When the true GMR = 1.0 then, without additional
      constraints, the sample size is independent of the intrasubject variation. When
      the true GMR is increased or decreased from 1.0 then the required sample sizes
      rise at above but close to 30% variation. An additional regulatory constraint on
      the point estimate of GMR and a cap on the use of expanding limits further
      increase the required sample size at high variations. Fewer subjects are required
      by the FDA than by the EMA procedures. CONCLUSIONS: The methods proposed by EMA
      and FDA lower the required sample sizes in comparison with unscaled average BE.
      However, each additional regulatory requirement (applying the mixed procedure,
      imposing a constraint on the point estimate of GMR, and using a cap on the
      application of expanding limits) raises the required number of subjects.

PMID- 22365090
TI  - Swim training reduces metformin levels in fructose-induced insulin resistant
      rats.
AB  - PURPOSE: Regular exercise training and metformin medication are widely considered
      to increase insulin sensitivity and protect against type 2 diabetes, however,
      evaluating the effect of exercise training on the disposition and
      pharmacokinetics of metformin is unclear. METHODS: We investigated the effect of
      a 4-wk swim training program (45 min/day, 5 days/wk) on the pharmacokinetics for
      the use of metformin in fructose-induced insulin resistant rats. Fructose-induced
      insulin resistant rats were assigned into two groups (n=6/group): swim training
      with metformin (SM), and non-swim training with metformin (CM). Blood samples
      were collected from 12 h-fasted rats at baseline and at 0.25, 0.5, 0.75, 1, 2, 3,
      4, 6, 8, 10, and 12 h after an oral glucose tolerance test (OGTT) with
      administration of a single dose of metformin (450 mg/kg). RESULTS: Our study
      revealed that both glucose and insulin levels in the SM group were significantly
      lower than those in the CM group at 15 min following OGTT. The maximum
      concentration (C(max)) and area under the serum concentration-time curve (AUC)
      for the SM group were significantly lower than CM group. The apparent
      distribution volume (Vd) and the time-averaged total body clearance (CL) for the
      SM group were significantly higher than those for the CM group. There were no
      significant differences in the time to maximum concentration (T(max)) or the time
      to half-life concentration (t(1/2)) between the two groups. CONCLUSIONS: Our data
      demonstrate that swim training reduces metformin serum levels.

PMID- 22365091
TI  - Ginkgo extract EGb761 confers neuroprotection by reduction of glutamate release
      in ischemic brain.
AB  - PURPOSE: Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in
      various experimental models. In the present study, we demonstrate neuroprotective
      effects of EGb761 in experimental stroke while monitoring brain metabolism by
      microdialysis. METHODS: We have used oxygen-glucose deprivation in brain slices
      in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia
      in mouse brain. We used microdialysis in mouse striatum to monitor extracellular
      concentrations of glucose and glutamate. RESULTS: In vitro, EGb761 reduced
      ischemia-induced cell swelling in hippocampal slices by 60%. In vivo,
      administration of EGb761 (300 mg/kg) reduced cell degeneration and edema
      formation after MCAO by 35-50%. Immediately following MCAO, striatal glucose
      levels dropped to 25% of controls, and this reduction was not significantly
      affected by EGb761. Striatal glutamate levels, in contrast, increased 15-fold
      after MCAO; after pretreatment with EGb761, glutamate levels only increased by 4
      5fold. CONCLUSIONS: We show that pretreatment with EGb761 strongly reduces
      cellular edema formation and neurodegeneration under conditions of ischemia. The
      mechanism of action seems to be related to a reduction of excitotoxicity, because
      ischemia-induced release of glutamate was strongly suppressed. Ginkgo extracts
      such as EGb761 may be valuable to prevent ischemia-induced damage in stroke-prone
      patients.

PMID- 22365092
TI  - Nanosponges: a novel class of drug delivery system--review.
AB  - Effective targeted drug delivery systems have been a dream for a long time, but
      it has been largely frustrated by the complex chemistry that is involved in the
      development of new systems. The invention of nanosponges has become a significant
      step toward overcoming these problems. Nanosponges are tiny sponges with a size
      of about a virus, which can be filled with a wide variety of drugs. These tiny
      sponges can circulate around the body until they encounter the specific target
      site and stick on the surface and begin to release the drug in a controlled and
      predictable manner. Because the drug can be released at the specific target site
      instead of circulating throughout the body it will be more effective for a
      particular given dosage. Another important character of these sponges is their
      aqueous solubility; this allows the use of these systems effectively for drugs
      with poor solubility.

PMID- 22365093
TI  - Potential renoprotective effects of silymarin against nephrotoxic drugs: a review
      of literature.
AB  - Drug-induced nephrotoxicity (DIN) accounts for up to sixty percent of hospital
      acquired acute kidney injury. Several efforts have been made to reduce drug
      induced renal damage; however, DIN remains a matter of concern, with substantial
      impact on patients and the health system. Silymarin is a drug that has been used
      for many years in alternate and modern medicine for treating hepatic diseases.
      Its antioxidant, anti-inflammatory and anti-apoptotic effects make it an
      interesting herbal medicine, and these properties have implicated this compound
      as a potential renoprotective agent. Based on the findings from animal studies,
      this review concluded that silymarin might exert significant protective or
      ameliorative effects against drug-induced kidney disease, especially against
      cisplatin-induced renal damage. Whether the protective administration of
      silymarin could be an effective clinical pharmacological strategy to prevent DIN
      is a question that remains to be answered in clinical trials.

PMID- 22365094
TI  - Organic glues or fibrin glues from pooled plasma: efficacy, safety and potential
      as scaffold delivery systems.
AB  - Since 1976, fibrin glues have been attracting medical interest, spreading from
      their initial use as a hemostatic agent in cardiovascular surgery to other fields
      of surgery. Studies have compared the efficacy of fibrin glues vs sutures in
      surgery. However, few comparisons have been made of the efficacy and safety of
      the different fibrin glues commercially available. Recently, fibrin glues have
      been tested as a scaffold delivery system for various substances inside the body
      (drugs, growth factors, stem cells). The infectious risk (viruses, new germs) of
      this blood-derived product was also studied in assays on viral inactivation
      methods. The development of autologous fibrin glues offers a solution to the
      problem of infectious risk. This review examines the current state of knowledge
      on the efficacy, safety and future potential of fibrin glues.

PMID- 22365095
TI  - alpha-Amylase inhibitors: a review of raw material and isolated compounds from
      plant source.
AB  - Inhibition of alpha-amylase, enzyme that plays a role in digestion of starch and
      glycogen, is considered a strategy for the treatment of disorders in carbohydrate
      uptake, such as diabetes and obesity, as well as, dental caries and periodontal
      diseases. Plants are an important source of chemical constituents with potential
      for inhibition of alpha-amylase and can be used as therapeutic or functional food
      sources. A review about crude extracts and isolated compounds from plant source
      that have been tested for alpha-amylase inhibitory activity has been done. The
      analysis of the results shows a variety of crude extracts that present alpha
      amylase inhibitory activity and some of them had relevant activity when compared
      with controls used in the studies. Amongst the phyto-constituents that have been
      investigated, flavonoids are one of them that demonstrated the highest inhibitory
      activities with the potential of inhibition related to number of hydroxyl groups
      in the molecule of the compound. Several phyto-constituents and plant species as
      alpha-amylase inhibitors are being reported in this article. Majority of studies
      have focused on the anti-amylase phenolic compounds.

PMID- 22365096
TI  - Development and characterization of niosomal formulations of doxorubicin aimed at
      brain targeting.
AB  - PURPOSE: The aim of the present work was the development and characterization of
      a niosomal formulation functionalized with the glucose-derivative N
      palmitoylglucosamine (NPG) to obtain a potential brain targeted delivery system
      for the anticancer agent doxorubicin. METHODS: Five different methods have been
      examined for vesicle preparation. Light scattering and transmission electron
      microscopy were used for vesicle characterization, in terms of mean size,
      homogeneity and Zeta potential, and selection of the best composition and
      preparation conditions for developing NPG-functionalized niosomes. Drug
      entrapment efficiency was determined after separation of loaded from unloaded
      drug by size exclusion chromatography or dialysis. Preliminary in vivo studies
      were performed on rats, injected i.v. with 12 mg/kg of doxorubicin as commercial
      solution (Ebewe, 2 mg/mL) or NPG-niosomal formulation. Drug amounts in the blood
      and in the major organs of the animals, sacrificed 60 min post injection, were
      determined by HPLC. RESULTS: The selected formulation consisted in
      Span:cholesterol:Solulan:NPG (50:40:10:10 mol ratio) vesicles obtained by thin
      layer evaporation, leading to homogeneous vesicles of less than 200 nm diameter.
      This formulation was used for preparation of NPG-niosomes loaded with doxorubicin
      (mean size 161+/-4 nm, encapsulation efficacy 57.8+/-1.8%). No significant
      changes (P>0.05) in vesicle dimensions, Zeta potential or entrapment efficiency
      were observed after six months storage at room temperature, indicative of good
      stability. I.v. administration to rats of the NPG-niosomal formulation allowed
      for reducing drug accumulation in the heart and keeping it longer in the blood
      circulation with respect to the commercial formulation. Moreover, a doxorubicin
      brain concentration of 2.9+/-0.4 MUg/g was achieved after 60 min, while the
      commercial solution yielded undetectable drug brain concentrations (<0.1 MUg/g).
      CONCLUSIONS: The developed NPG-niosomal formulation gave rise to stable, nano
      sized vesicles, able to improve doxorubicin brain delivery. Positive results of
      preliminary in vivo studies require future pharmacokinetic studies to gain more
      insight into the mechanism of drug transport of functionalized niosomes.

PMID- 22365097
TI  - Drug delivery properties of macroporous polystyrene solid foams.
AB  - PURPOSE: Polymeric porous foams have been evaluated as possible new
      pharmaceutical dosage forms. METHODS: These materials were obtained by
      polymerization in the continuous phase of highly concentrated emulsions prepared
      by the phase inversion temperature method. Their porosity, specific surface and
      surface topography were characterized, and the incorporation and release of
      active principles was studied using ketoprofen as model lipophilic molecule.
      RESULTS: Solid foams with very high pore volume, mainly inside macropores, were
      obtained by this method. The pore morphology of the materials was characterized,
      and very rough topography was observed, which contributed to their nearly
      superhydrophobic properties. These solid foams could be used as delivery systems
      for active principles with pharmaceutical interest, and in the present work
      ketoprofen was used as a model lipophilic molecule. CONCLUSIONS: Drug
      incorporation and release was studied from solid foam disks, using different
      concentrations of the loading solutions, achieving a delayed release with short
      lag-time.

PMID- 22365098
TI  - Low back pain post partum - a case report.
AB  - Sacral stress fracture is an unusual source of low back pain and can be easily
      confused with a number of other clinical conditions seen in physiotherapy
      clinics. The purpose of this case report is to describe the case of a patient
      presenting with low back pain post partum illustrating pertinent aspects of
      differential diagnosis and issues of management. A 31 year old female presented
      complaining of low back pain since the birth of her second child 11 months
      earlier. Subjective and objective examination led the Therapist to consider a
      diagnosis of sacral stress fracture. This diagnosis was confirmed by MRI. Three
      months after presenting to physiotherapy the patient was pain free and had
      returned to all aspects of her daily life without any difficulties. Clinicians
      must be aware of the less common pathologies in any hypotheses development. A
      careful history and physical examination and broad hypotheses generation will
      ensure that patients are accurately diagnosed and receive appropriate and
      effective treatments.

PMID- 22365099
TI  - Tale of two sites: capillary versus arterial blood glucose testing in the
      operating room.
AB  - INTRODUCTION: Pre- and intraoperative glycemic control has been identified as a
      putative target to improve outcomes of surgical patients. Glycemic control
      requires frequent monitoring of blood glucose levels with appropriate
      adjustments. However, monitoring standards have been called into question,
      especially in cases in which capillary samples are used. Point-of-care testing
      (POCT) using capillary samples and glucometers has been noted to give relatively
      accurate results for critically ill patients. However, the package inserts of
      most glucometers warn that they should not be used for patients in shock. This
      has led clinicians to doubt their accuracy in the operating room. The accuracy of
      capillary samples when tested in patients undergoing surgical procedures has not
      been proven. This study aims to determine the accuracy of intraoperative blood
      glucose values using capillary samples relative to arterial samples. METHODS: A
      prospective study was conducted by collecting paired capillary and arterial
      samples of patients undergoing major operations at a tertiary medical center from
      August 2009 to May 2011. Subjects were a convenience sample of patients who had
      arterial lines and needed glucose testing while undergoing the procedure.
      Precision Xceed Pro (Abbott) handheld glucometers were used to obtain the blood
      glucose values. Our primary outcome of interest was the degree of correlation
      between capillary and arterial blood glucose values or the degree to which
      arterial glucose levels can be predicted by capillary glucose samples. We used
      linear regression and the Student t tests for statistical analyses. RESULTS:
      Seventy-two-paired samples were collected. Of the cases, 54% were major abdominal
      operations, whereas 24% were vascular operations. The mean values +/- standard
      deviation for glucose levels were 146 +/- 35 mg/dL (capillary) and 147 +/- 36
      mg/dL (arterial). The mean time +/- standard deviation between the collection of
      both samples was 3.5 +/- 1.3 minutes. The regression coefficient showed a strong
      positive correlation of .91 between capillary glucose values and arterial values
      (P < .001) although correlation was less stringent at the hyperglycemic range of
      values. The R(2) statistic was 84%. Differences in values between capillary and
      arterial samples would not have altered the diagnosis of hypo- and hyperglycemia
      using typical thresholds. CONCLUSIONS: Capillary samples collected
      intraoperatively are strongly correlated with arterial samples. Glucose
      monitoring in the operating room can be safely performed by collecting capillary
      samples for POCT. However, clinicians should still be cautious when interpreting
      glucose levels that are high, either by repeating the blood glucose test or by
      having samples sent to the laboratory.

PMID- 22365100
TI  - [Angiosarcoma in chronic lymphedema (Stewart-Treves syndrome)].

PMID- 22365101
TI  - [How do women in puerperium perceive the care received in the obstetrics
      department of the Albacete (Spain) hospital complex?].
AB  - AIM: To describe the level of satisfaction of women who come to the University
      Hospital of Albacete (CHUA), as regards the health carereceived upon admission
      for giving birth and during the immediate postnatal period, and to evaluate if
      the socio-demographic variable has an influence on user satisfaction of the
      delivery room service. METHOD: Descriptive and cross-sectional study carried out
      through an interview in order to obtain data on the socio-demographic, obstetric
      and gynaecological variables, together with a satisfaction questionnaire for
      women in the puerperium period at the CHUA, reference hospital of the Health Area
      in Albacete, in the Obstetrics Service. The selection was made by systematic
      sampling, in which immigrants and Spanish born women were enrolled according to
      the inclusion criteria. RESULTS: We found that 92.1% (164) of Spanish-born women
      carry out a proper integral control of pregnancy, compared to 63.4% (109) of
      immigrants (chi(2)=42.172; gl=1; P=.000). The majority (87.5%, 287) of the total
      number of satisfied women thought that the midwife interest was better or much
      better than they expected (chi(2)=102.466; gl=4; P=.000). The large majority of
      satisfied women (95.81%, 320) would recommend the hospital, while the number of
      unsatisfied women had doubts (chi(2)=93.680; gl=2; P=.000). CONCLUSIONS: The
      socio-demographic variables did not appear to have an influence on the overall
      satisfaction of the women, except for the age. In general, both the autochthonous
      and immigrant women were satisfied with the attention received in the CHUA
      Delivery room.

PMID- 22365102
TI  - [Breast cancer survivors: quality of life and prevailing diagnoses].
AB  - Knowledge of the Quality of Life (QoL) of surviving patients with breast cancer
      using an effective tool, and adapting it to nursing language using NANDA
      taxonomy, is essential to identify their needs and health problems. OBJECTIVES:
      To evaluate the QoL of women diagnosed with breast cancer in 2004 (survivors). To
      identify the most common health problems, and adapting them to the NANDA
      taxonomy. METHODOLOGY: A cross-sectional descriptive study was conducted using a
      QoL Survey (EORTC QLQ-C30 and BR23) in breast cancer survivors with the
      collection of demographic and clinical data (October-December 2009). Descriptive
      statistics (SPSS 18.0) were performed, as well as an analysis of the responses to
      questionnaire items, identifying defining characteristics, related factors and
      actual/potential diagnoses (NANDA taxonomy). RESULTS: The study included 140
      participants. There was a significant effect on: Sexual Function (23.16 +/-
      25.85), Sexual Enjoyment (48.3 +/- 29.15), Concern for the future (51.63 +/-
      32.32), insomnia (33.03 +/- 33.91) and Concern for hair loss (32.67 +/- 33.67).
      The most prevalent health problems were: inefficient sexual pattern (87.1%), body
      image disorder (80.7%), anxiety (41.5) and sexual dysfunction (31.7%). The
      relationship between these, the defining characteristics, the related factors and
      key questionnaire items for their identification are shown. DISCUSSION: The QoL
      of breast cancer survivors is affected in various fields. The EORTC scale can be
      used as a focused evaluation of QoL. Evidence is provided on the most prevalent
      diagnoses in survivors, being a first step towards standardisation of care.
      Research on nursing interventions aimed at improving the QOL of patients is
      necessary.

PMID- 22365103
TI  - Methods in health systems and policy research.

PMID- 22365104
TI  - The nursing profession and patient safety and healthcare provider influenza
      immunization: the puzzling stance of the American Nursing Association.

PMID- 22365105
TI  - Nursing leadership to ensure patient and health worker protection from influenza.

PMID- 22365106
TI  - Copper(II)-based metal affinity chromatography for the isolation of the
      anticancer agent bleomycin from Streptomyces verticillus culture.
AB  - The glycopeptide-based bleomycins are structurally complex natural products
      produced by Streptomyces verticillus used in combination therapy against
      testicular and other cancers. Bleomycin has a high affinity towards a range of
      transition metal ions with the 1:1 Fe(II) complex relevant to its mechanism of
      action in vivo and the 1:1 Cu(II) complex relevant to its production from
      culture. The affinity between Cu(II) and bleomycin was the underlying principle
      for using Cu(II)-based metal affinity chromatography in this work to selectively
      capture bleomycin from crude S. verticillus culture. A solution of standard
      bleomycin was retained at a binding capacity of 300 nmol mL(-1) on a 1-mL bed
      volume of Cu(II)-loaded iminodiacetate (IDA) resin at pH 9 via the formation of
      the heteroleptic immobilized complex [Cu(IDA)(bleomycin)]. Bleomycin was eluted
      from the resin at pH 5 as the metal-free ligand under conditions where pK(a)
      (IDA)<pH<pK(a) beta-hydroxyhistidine amide (bleomycin). Bleomycin was captured on
      a Cu(II)-loaded IDA resin at pH 9 in 50% yield from bleomycin-containing S.
      verticillus culture that was pre-processed using XAD-2 resin to remove
      endogenously bound Cu(II). The approximate 25-fold purification of bleomycin from
      complex culture supernatant under aqueous conditions in a single step
      demonstrates the potential of Cu(II)-based metal affinity chromatography as a
      green chemistry platform for streamlined access to this high-value therapeutic
      agent.

PMID- 22365107
TI  - Glucocorticoid and calcitonin receptor expression in central giant cell lesions:
      implications for therapy.
AB  - Central giant cell lesion is an uncommon benign jaw lesion, with uncertain
      aetiology, and variable clinical behaviour. Studies of molecular markers may help
      to understand the nature and behaviour of this lesion, and eventually may
      represent a target for pharmacological approaches to treatment. The aim of this
      study was to analyse the expression of glucocorticoid and calcitonin receptors in
      central giant cell lesions before and after treatment with intralesional steroid.
      Paraffin-embedded blocks from patients who underwent treatment with intralesional
      triamcinolone hexacetonide injections were stained immunohistochemically.
      Biological material from patients who underwent a surgical procedure after
      treatment were tested immunohistochemically. 18 cases (9 aggressive and 9 non
      aggressive) were included. The difference in calcitonin receptor expression was
      not statistically significant between the aggressive and non-aggressive lesions
      and between the patients with a good response and those with a moderate/negative
      response to treatment. Glucocorticoid receptor expression in the multinucleated
      giant cells was higher in patients with a good response. It can be postulated
      that immunohistochemical staining for glucocorticoid receptors may provide a tool
      for selecting the therapeutic strategy. An H-score greater than 48 for
      glucocorticoid receptors in multinucleated giant cells predicted a good response
      in this study.

PMID- 22365108
TI  - Seronegative myasthenia gravis with bladder dysfunction.

PMID- 22365109
TI  - Low linoleic acid may facilitate Delta6 desaturase activity and docosahexaenoic
      acid accretion in human fetal development.
AB  - The n-3 and n-6 fatty acids are transferred across the placenta with consistently
      higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought
      to determine whether maternal and fetal cord blood red blood cell (RBC)
      phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed
      the relationship between 18:2n-6 and Delta6 desaturase product/precursor ratios
      for 97 mothers and newborns. Despite higher fetal than maternal plasma
      phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed
      similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of
      failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma
      phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6
      was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and
      18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be
      a specific mechanism to prevent inhibition of fetal Delta6 desaturase and
      facilitate fetal cellular phospholipid 22:6n-3 accretion.

PMID- 22365111
TI  - High-efficiency microstructured semiconductor neutron detectors that are arrayed,
      dual-integrated, and stacked.
AB  - Silicon diodes with large aspect ratio 3D microstructures backfilled with 6LiF
      show a significant increase in neutron detection efficiency beyond that of
      conventional thin-film coated planar devices. Described in this work are
      advancements in the technology using detector stacking methods and summed
      detector 6*6-element arraying methods to dramatically increase the sensitivity to
      thermal neutrons. The intrinsic detection efficiency of the 6*6 array for normal
      incident 0.0253 eV neutrons was found 6.8% compared against a calibrated 3He
      proportional counter.

PMID- 22365110
TI  - [Pyogenic liver abscess: clinical presentation and predictors of unfavorable
      outcome].
AB  - OBJECTIVES: To describe the clinical features of pyogenic liver abscesses (PLA)
      and identify the factors associated with an unfavorable outcome. MATERIAL AND
      METHODS: We performed a retrospective review of the clinical histories of
      patients with liver abscess (1996-2009), including those that met the diagnostic
      criteria for PLA. Outcome was classified as favorable or unfavorable (severe
      sepsis, distant infectious complications, local complications, intensive care
      unit admission, admission for>30 days, death, readmission). RESULTS: There were
      54 patients with PLA (65% men), with a mean age of 61 years. Predisposing factors
      consisted of biliopancreatic disease in 33%, recent admission in 20%, alcoholism
      in 15%, diabetes mellitus in 15%, a history of gastrointestinal neoplasm in 11%
      and abdominal surgery in 11%. The cause was cryptogenic in 65%, biliary in 31%,
      and portal in 4%. Symptoms consisted of fever in 100%, abdominal pain in 65%,
      vomiting in 37%, enlarged liver in 33%, systemic inflammatory response syndrome
      in 26%, and jaundice in 9%. Blood and pus cultures were positive in 40% and 65%,
      respectively. The most frequently isolated microorganisms were E. coli and
      Streptococcus spp. Percutaneous drainage was performed in 72% (surgical drainage
      was also performed in 6%), and antibiotic treatment alone was administered in
      28%. Outcome was unfavorable in 52% and was associated with greater age
      (p=0.016), a history of biliopancreatic disease (p=0.007), systemic inflammatory
      response syndrome at diagnosis (p=0.005), coagulation alterations (p=0.043),
      aspartate aminotransferase elevation (p=0.033), and biliary etiology (p<0.001).
      CONCLUSIONS: PLA developed in patients with comorbidity, although most were
      cryptogenic. The majority of PLA were resolved with antibiotic therapy and
      percutaneous drainage, without surgery. Mortality was 9%, but half the patients
      had unfavorable outcome, associated with biliary etiology and some laboratory
      alterations.

PMID- 22365112
TI  - A simple approach for EPID dosimetric calibration to overcome the effect of image
      lag and ghosting.
AB  - EPID dosimetry has known drawbacks. The main issue is that a measurable residual
      signal is observed after the end of irradiation for prolonged periods of time,
      thus making measurement difficult. We present a detailed analysis of EPID
      response and suggest a simple, yet accurate approach for calibration that avoids
      the complexity of incorporating ghosting and image-lag using the maximum
      integrated signal instead of the total integrated signal. This approach is linear
      with dose and independent of dose rate.

PMID- 22365113
TI  - Hierarchical dendritic gold microstructure-based aptasensor for ultrasensitive
      electrochemical detection of thrombin using functionalized mesoporous silica
      nanospheres as signal tags.
AB  - A sensitive electrochemical approach for the detection of thrombin was designed
      by using densely packed hierarchical dendritic gold microstructures (HDGMs) with
      secondary and tertiary branches as matrices, and thionine-functionalized
      mesoporous silica nanospheres as signal tags. To prepare the signal tags, the
      positively charged thionine (as an indicator) was initially adsorbed onto the
      mesoporous silica nanoparticles (MSNs). Then [AuCl(4)](-) ions were in situ
      reduced on the thionine-modified MSNs by ascorbic acid to construct nanogold
      decorated MSNs (GMSNs). The formed GMSNs were employed as label of the aminated
      aptamers. The assay was carried out in PBS, pH 7.4 with a sandwich-type assay
      mode by using the assembled thionine in the GMSNs as indicators. Compared with
      the pure silica nanoparticles, mesoporous silica could provide a larger surface
      for the immobilization of biomolecules and improve the sensitivity of the
      aptasensor. Under optimal conditions, the electrochemical aptasensors exhibited a
      wide linear range from 0.001 to 600 ng mL(-1) (i.e. 0.03 pM to 0.018 MUM
      thrombin) with a low detection limit (LOD) of 0.5 pg mL(-1) (~15 fM) thrombin at
      3sigma. No obvious non-specific adsorption was observed during a series of
      analyses to detect target analyte. The precision, selectivity and stability of
      the aptasensors were acceptable. Importantly, the methodology was evaluated with
      thrombin spiked samples in blank fetal calf serum, and the recoveries were 94.2
      112%, indicating an exciting potential for thrombin detection.

PMID- 22365114
TI  - Certified reference materials for analytical mercury speciation in biological and
      environmental matrices: do they meet user needs?; a review.
AB  - The usefulness of a certified reference material (CRM) for analytical method
      validation and quality control purposes is attributed mainly to its key
      properties, namely homogeneity and stability. However, it is also advisable to
      select suitable CRMs in terms of representativeness. To assess the
      representativeness of a CRM for analytical mercury speciation, a number of
      aspects must be considered in regard to the routine samples analyzed: the origin
      of the matrix, the type of mercury species and the level of concentration. This
      review critically analyzes the availability of current CRMs for mercury
      speciation analysis in environmental and biological fields. The characteristics
      of the CRMs are compared with the matrices and samples covered in papers
      published in the last five years on mercury speciation, mainly in water, soils,
      sediments, sewage sludge, seafood, blood, urine and hair.

PMID- 22365115
TI  - Neutral losses: a type of important variables in prediction of branching degree
      for acyclic alkenes from mass spectra.
AB  - Neutral losses are a type of important variables in mass spectral interpretation.
      Since it is hard to calculate or extract neutral losses from mass spectra, they
      are usually discarded. In this study, dissimilarity analysis was employed to
      extract mass spectral characteristics for predicting branching degree of acyclic
      alkenes. The relationships between branching degree and neutral loss were
      constructed under direction of experimental observation and mass spectral
      fragmentations. A branching degree predictor of acyclic alkenes was subsequently
      built based on the above relationships. After tested by the experimental data in
      previous studies, the predictor could correctly provide the branching degree from
      abundant ions of mass spectra. More importantly, this predictor was able to point
      out which acyclic alkenes could be predicted correctly or not.

PMID- 22365116
TI  - NIR analysis for batch process of ethanol precipitation coupled with a new
      calibration model updating strategy.
AB  - Ethanol precipitation plays a major role in the pretreatment of Flos Lonicerae
      Japonicae of Qingkailing injection, and is also one of the most popular
      purification techniques in Chinese herbal medicines. In order to monitor and have
      a better understanding of the ethanol precipitation process, a PLS model was
      built based on NIR spectroscopy and HPLC analysis of chlorogenic acid content
      within the framework of FDA's PAT initiative. Nevertheless, due to the complex
      mechanism of and the raw materials' natural variability introduced into the
      ethanol precipitation process, it was unable to foresee the variations in new
      batches which may jeopardize the robustness of the established model. Therefore,
      based on the simple interval calculation (SIC) theory, a new model expansion
      updating strategy which could continuously expand the variation coverage of the
      calibration model along with the batch proceeding of ethanol precipitation
      process was proposed. Effects of model updating were validated by an individual
      batch with 60 samples. After two times of updating, the root mean squared error
      of prediction (RMSEP) decreased from 0.268 mg mL(-1) to 0.199 mg mL(-1), while
      the insiders in the object status plot (OSP) increased from 44 to 58,
      demonstrating the good performance of the proposed approach.

PMID- 22365117
TI  - Electropolymerized surface ion imprinting films on a gold nanoparticles/single
      wall carbon nanotube nanohybrids modified glassy carbon electrode for
      electrochemical detection of trace mercury(II) in water.
AB  - Electrochemical detection of Hg(II) using a electropolymerized ion imprinting
      poly(2-mercaptobenzothiazole) films at the surface of gold nanoparticles/single
      walled carbon nanotube nanohybrids modified glassy carbon electrode
      (PMBT/AuNPs/SWCNTs/GCE) is described for the first time. The Hg(II)-imprinted
      PMBT/AuNPs/SWCNTs/GCE sensor exhibits larger binding to functionalized capacity,
      larger affinity, faster binding kinetics and higher selectivity to template
      Hg(II). The differential pulse anodic stripping voltammetry (DPASV) response of
      the Hg(II)-imprinted PMBT/AuNPs/SWCNTs/GCE sensor to Hg(II) is ca. 3.7- and 10.5
      fold higher than that at the non-imprinted PMBT/AuNPs/SWCNTs/GCE and the
      imprinted PMBT/AuNPs/GCE, respectively, and the detection limit for Hg(II) is
      0.08 nM (S/N=3, which is well below the guideline value given by the World Health
      Organization) and a sensitivity of 0.749 MUA nM(-1) was obtained. Excellent wide
      linear range (0.4-96.0 nM) and good repeatability (relative standard deviation of
      2.6%) were obtained for Hg(II). The interference experiments show that Ag(I),
      Pb(II), Cd(II), Zn(II) and Cu(II) had little or no influence on the Hg(II)
      signal. These values, particularly the high sensitivity and excellent selectivity
      in contrast to the values reported previously in the area of electrochemical
      Hg(II) detection, demonstrate the analytical performance of the Hg(II)-imprinted
      PMBT/AuNPs/SWCNTs/GCE toward Hg(II) is superior to the existing electrodes and
      could be used for efficient determination of Hg(II) in natural water samples.

PMID- 22365118
TI  - Immobilization of tris(1,10-phenanthroline)ruthenium with graphene oxide for
      electrochemiluminescent analysis.
AB  - Electrochemiluminescence (ECL) of ruthenium complexes has broad applications and
      the immobilization of Ru(bpy)(3)(2+) has received extensive attention. In
      comparison with Ru(bpy)(3)(2+), Ru(phen)(3)(2+) can be immobilized more easily
      because of its better adsorbability. In this study, immobilization of
      Ru(phen)(3)(2+) for ECL analysis has been demonstrated for the first time by
      using graphene oxide (GO) as an immobilization matrix. The immobilization of
      Ru(phen)(3)(2+) is achieved easily by mixing Ru(phen)(3)(2+) with GO without
      using any ion exchange polymer or covalent method. The strong binding of
      Ru(phen)(3)(2+) with GO is attributed to both the pi-pi stacking interaction and
      the electrostatic interaction. The Ru(phen)(3)(2+)/GO modified electrode was
      characterized by using tripropylamine (TPA) as the coreactant. The linear range
      of TPA is from 3*10(-7) to 3*10(-2) mol L(-1) with the detection limit of 3*10(
      7) mol L(-1). The ECL sensor demonstrates outstanding long-term stability. After
      the storage in the ambient environment for 90 days, the ECL response remains
      comparable with its original signal.

PMID- 22365119
TI  - Impedimetric immunosensor for human serum albumin detection on a direct aldehyde
      functionalized silicon nitride surface.
AB  - In this work we report the fabrication and characterization of a label-free
      impedimetric immunosensor based on a silicon nitride (Si(3)N(4)) surface for the
      specific detection of human serum albumin (HSA) proteins. Silicon nitride
      provides several advantages compared with other materials commonly used, such as
      gold, and in particular in solid-state physics for electronic-based biosensors.
      However, few Si(3)N(4)-based biosensors have been developed; the lack of an
      efficient and direct protocol for the integration of biological elements with
      silicon-based substrates is still one of its the main drawbacks. Here, we use a
      direct functionalization method for the direct covalent binding of monoclonal
      anti-HSA antibodies on an aldehyde-functionalized Si-p/SiO(2)/Si(3)N(4)
      structure. This methodology, in contrast with most of the protocols reported in
      literature, requires less chemical reagents, it is less time-consuming and it
      does not need any chemical activation. The detection capability of the
      immunosensor was tested by performing non-faradaic electrochemical impedance
      spectroscopy (EIS) measurements for the specific detection of HSA proteins.
      Protein concentrations within the linear range of 10(-13)-10(-7) M were detected,
      showing a sensitivity of 0.128 Omega MUM(-1) and a limit of detection of 10(-14)
      M. The specificity of the sensor was also addressed by studying the interferences
      with a similar protein, bovine serum albumin. The results obtained show that the
      antibodies were efficiently immobilized and the proteins detected specifically,
      thus, establishing the basis and the potential applicability of the developed
      silicon nitride-based immunosensor for the detection of proteins in real and more
      complex samples.

PMID- 22365120
TI  - Amperometric enzyme electrodes of glucose and lactate based on
      poly(diallyldimethylammonium)-alginate-metal ion-enzyme biocomposites.
AB  - Sodium alginate (AlgNa) and poly(diallyldimethylammonium chloride) (PDDA) were
      mixed to obtain an interpenetrating polymer composite via electrostatic
      interaction and then cast on an Au electrode surface, followed by incorporation
      of metal ions (e.g. Fe(3+) or Ca(2+), to form AlgFe or AlgCa hydrogel) and
      glucose oxidase (GOx) (or lactate oxidase (LOx)), to prepare amperometric enzyme
      electrodes. The interactions of PDDA, Alg, and Fe(3+) are studied by visual
      inspection as well as microscopic and electrochemical methods. Under optimized
      conditions, the PDDA-AlgFe-enzyme/Au and PDDA-AlgCa-enzyme/Au electrodes can give
      good analytical performance (e.g. nM-scale limit of detection of glucose or
      lactate, and sensitivities > 50 MUA cm(-2) mM(-1)) in the first-generation
      biosensing mode, which are better than the reported analogs using typical
      polysaccharide biopolymers as enzyme-immobilization matrices. The enzyme
      electrodes also worked well in the second-generation biosensing mode in the
      coexistence of p-benzoquione or ferrocene monocarboxylic acid artificial
      mediator. Biofuel cells (BFCs) with the enzyme electrodes as the bioanodes and
      glucose (or lactate) as the biofuel were also fabricated with satisfactory
      results. The proposed protocols for preparation of high performance Alg-based
      biocomposites may find wide applications in bioanalysis.

PMID- 22365121
TI  - Facile synthesis of magnetic one-dimensional polyaniline and its application in
      magnetic solid phase extraction for fluoroquinolones in honey samples.
AB  - In this work, we proposed a simple co-mixing method to fabricate magnetic one
      dimensional polyaniline (denoted as 1D-PANIs/MNPs). One-dimensional polyanilines
      (1D-PANIs) and magnetic nanoparticles (MNPs) were prepared by chemical oxidation
      and solvothermal methods, respectively. When MNPs and 1D-PANIs (with mass ratio
      4:1) were co-mixed and vortexed evenly in a solvent (e.g., ethanol, water,
      acetonitrile), they could assemble into 1D-PANIs/MNPs spontaneously and thus be
      magnetically separable. To testify the feasibility of 1D-PANIs/MNPs in sample
      preparation, it was applied as the sorbent for magnetic solid phase extraction
      (MSPE) of fluoroquinolones (FQs) in honey samples. Under optimized conditions, a
      rapid, convenient, and efficient method for the determination of four FQs in
      honey samples by 1D-PANIs/MNPs-based MSPE coupling with high performance liquid
      chromatography with fluorescence detection (HPLC-FLD) was established. The limits
      of detection (LODs) for four FQs ranged from 0.4 to 1.4 ng g(-1). The intra- and
      interday relative standard deviations (RSDs) were less than 17.6%. The recoveries
      of FQs for three spiked honey samples ranged from 86.3 to 121.3%, with RSDs of
      less than 16.3%.

PMID- 22365122
TI  - Hydrophobic polymer monoliths as novel phase separators: application in
      continuous liquid-liquid extraction systems.
AB  - Hydrophobic macroporous polymer monoliths are shown to be interesting materials
      for the construction of "selective solvent gates". With the appropriate surface
      chemistry and porous properties the monoliths can be made permeable only for
      apolar organic solvents and not for water. Different poly(butyl methacrylate-co
      ethylene dimethacrylate) (BMA-EDMA) and poly(styrene-co-divinylbenzene) (PS-DVB)
      monoliths prepared with tailored chemistries and porosities were evaluated for
      this purpose. After extensive characterization, the PS-DVB monoliths were
      selected due to their higher hydrophobicity and their more suitable flow
      characteristics. BMA-EDMA monoliths are preferred for mid-polarity solvents such
      as ethyl acetate, for which they provide efficient separation from water.
      Breakthrough experiments confirmed that the pressures necessary to generate flow
      of organic solvents through PS-DVB monoliths were substantially lower than for
      water. A phase separator was constructed using the monoliths as the flow
      selector. This device was successfully coupled on-line with a chip-based
      continuous liquid-liquid-extraction (LLE) system with segmented flow. Efficient
      separation of different solvents was obtained across a wide range of flow rates
      (0.5-4.0 mL min(-1)) and aqueous-to-organic flow ratios (beta=1-10). Good
      robustness and long life-time were also confirmed. The suitability of the device
      to perform simple, cheap, and reliable phase separation in a continuous LLE
      system prior to gas-chromatographic analysis was proven for some selected real
      life applications.

PMID- 22365123
TI  - A novel superparamagnetic surface molecularly imprinted nanoparticle adopting
      dummy template: an efficient solid-phase extraction adsorbent for bisphenol A.
AB  - Leakage of the residual template molecules is one of the biggest challenges for
      application of molecularly imprinted polymer (MIP) in solid-phase extraction
      (SPE). In this study, bisphenol F (BPF) was adopted as a dummy template to
      prepare MIP of bisphenol A (BPA) with a superparamagnetic core-shell nanoparticle
      as the supporter, aiming to avoid residual template leakage and to increase the
      efficiency of SPE. Characterization and test of the obtained products (called mag
      DMIP beads) revealed that these novel nanoparticles not only had excellent
      magnetic property but also displayed high selectivity to the target molecule BPA.
      As mag-DMIP beads were adopted as the adsorbents of solid-phase extraction for
      detecting BPA in real water samples, the recoveries of spiked samples ranged from
      84.7% to 93.8% with the limit of detection of 2.50 pg mL(-1), revealing that mag
      DMIP beads were efficient SPE adsorbents.

PMID- 22365124
TI  - Advances in humeomics: enhanced structural identification of humic molecules
      after size fractionation of a soil humic acid.
AB  - We size fractionated a soil humic acid (HA) by preparative high performance size
      exclusion chromatography (HPSEC) and evaluated the analytical capacity of
      humeomics to isolate and identify humic molecular components in the separated
      size-fractions. HA and its three size-fractions were chemically fractionated to
      extract non-covalently bound organosoluble compounds (ORG1), weakly ester-bound
      organosoluble (ORG2) and hydrosoluble constituents (AQU2), strongly ester-bound
      organosoluble components (ORG3), and final unextractable residues (RES4).
      According to their solubility, the extracts were characterized by either GC-MS or
      on-line thermochemolysis/GC-MS techniques. The humeomic sequence showed that the
      analytical yields of identified compounds in either ORG or AQU extracts of size
      fractions were invariably larger than for the unfractionated HA. This was
      attributed to a weaker conformational stability of humic suprastructures obtained
      by HPSEC fractionation, thereby enabling an improved separation and
      identification of single humic molecules. In line with the supramolecular
      understanding of humic substances, we found that hydrophobic compounds were
      mainly distributed in the largest size-fraction, while hydrophilic components
      were eluted in the smallest size-fraction. Furthermore, compounds with linear
      chains or stackable aromatic rings associated in regular structures were more
      abundant in the former fraction, whereas irregularly shaped compounds, that
      hindered association in larger size, were mostly found in the latter fraction.
      Thus the structural characteristics of single humic molecules determined their
      mutual association in humic suprastructures, as well as their conformational
      strength and shape. The lack of de novo synthesized macropolymers in the
      unfractionated soil humic matter was confirmed by the absence of RES4 fractions
      in the separated size-fractions. Our results indicate that humeomics capacity to
      reveal the complex molecular composition of humic suprastructures was
      significantly improved by subjecting humic matter to a preliminary HPSEC
      fractionation.

PMID- 22365125
TI  - Optimisation of beryllium-7 gamma analysis following BCR sequential extraction.
AB  - The application of cosmogenic (7)Be as a sediment tracer at the catchment-scale
      requires an understanding of its geochemical associations in soil to underpin the
      assumption of irreversible adsorption. Sequential extractions offer a readily
      accessible means of determining the associations of (7)Be with operationally
      defined soil phases. However, the subdivision of the low activity concentrations
      of fallout (7)Be in soils into geochemical fractions can introduce high gamma
      counting uncertainties. Extending analysis time significantly is not always an
      option for batches of samples, owing to the on-going decay of (7)Be (t(1/2)=53.3
      days). Here, three different methods of preparing and quantifying (7)Be extracted
      using the optimised BCR three-step scheme have been evaluated and compared with a
      focus on reducing analytical uncertainties. The optimal method involved carrying
      out the BCR extraction in triplicate, sub-sampling each set of triplicates for
      stable Be analysis before combining each set and coprecipitating the (7)Be with
      metal oxyhydroxides to produce a thin source for gamma analysis. This method was
      applied to BCR extractions of natural (7)Be in four agricultural soils. The
      approach gave good counting statistics from a 24 h analysis period (~10% (2sigma)
      where extract activity >40% of total activity) and generated statistically useful
      sequential extraction profiles. Total recoveries of (7)Be fell between 84 and
      112%. The stable Be data demonstrated that the extraction procedure had a high
      reproducibility (<1% RSD), thus gamma counting uncertainties dominated the
      overall uncertainty. In addition, extractions of soil equilibrated with stable Be
      at a concentration below the Cation Exchange Capacity (CEC) of the soil
      demonstrated that doubling the soil:solution ratio to enhance the mass of soil
      used in a sequential extraction scheme affects the apparent distribution of
      approximately 10% of the total Be. At high concentration, stable Be was found to
      be a poor proxy for (7)Be fallout in sequential extractions.

PMID- 22365126
TI  - Analysis of antibiotics from liquid sample using electrospray ionization-ion
      mobility spectrometry.
AB  - The recent findings of antibiotic residues in aquatic environment at trace level
      have gained much concern for the detrimental effect on ecological and human
      health due to bacterial resistance. Here, the feasibility of using electrospray
      ionization ion mobility spectrometry (ESI-IMS) for analysis antibiotics in liquid
      sample is demonstrated. Reduced mobilities and collision cross sections of 18
      antibiotics are experimentally measured and compared with theoretical values
      according to mass-mobility correlation. Gentamicin is used as an example to
      investigate the capability of ESI-IMS for multi-component analysis of
      antibiotics. Mixtures of antibiotics at different concentrations are analyzed.
      The estimated detection limit for amoxicillin is 0.7 mg L(-1) (70 pg) and the
      linear range of response maintains over two orders. This method will be a
      potential technique for the analysis of antibiotics in aquatic environment.

PMID- 22365127
TI  - Volatile composition and sensory properties of Vitis vinifera red cultivars from
      north west Spain: correlation between sensory and instrumental analysis.
AB  - The aroma and volatile composition of wines from five red cultivars from NW Spain
      (Brancellao, Mencia, Merenzao, Mouraton and Souson) have been studied by gas
      chromatography-mass spectrometry (GC-MS) and sensory descriptive analysis (SDA)
      during three consecutive vintages (2007-2009) in order to characterize these
      wines. In addition, relationships between the instrumental (volatile) and sensory
      variables were analyzed through the application of partial least squares
      regression (PLSR). Results revealed that the effect of "cultivar" was very
      important as a third of compounds (16 in total) varied significantly (P<=0.05)
      among varieties. Mencia wines presented the highest concentrations of gamma
      nonalactone, whereas Souson wines were the richest in monoterpene compounds. On
      the contrary, no significant difference was observed with respect to the esters
      content, probably as a consequence of using the same yeast for all vinifications.
      Twenty out of 51 quantified volatile compounds were present in some samples at
      concentrations higher than their corresponding odor thresholds (OAV>1), thus
      contributing to the final wine aroma. Partial least square (PLS) regression was
      applied to volatile compounds with OAV>0.2 and aroma descriptors with %GM>10.
      PLSR yielded a satisfactory model for the prediction of four important aroma
      descriptors in this set of wines--aroma quality, aroma intensity, herbaceous and
      red fruit--from instrumental analysis data. This work contributes to gaining
      knowledge about the sensory profiles and its relation to the volatile composition
      of minority Galician red grape cultivars.

PMID- 22365128
TI  - Preparation of strongly fluorescent silica nanoparticles of polyelectrolyte
      protected cadmium telluride quantum dots and their application to cell toxicity
      and imaging.
AB  - Based on the polyelectrolyte-protected CdTe quantum dots (QDs), which were
      prepared by self-assembling of QDs and poly-diallyldimethylammonium chloride
      (PDADMAC) in the help of electrostatic attraction, the strong fluorescence silica
      nanoparticles (QDs-PDADMAC@SiO(2)) have been prepared via a water-in-oil reverse
      microemulsion method. Transmission electron microscopy and Zeta potential
      analysis were used to characterize the as-prepared nanoparticles. All of the
      particles were almost spherical and there is a uniform distribution of the
      particle size with the average diameter about 25 nm. There is a large Zeta
      potential of -35.07 mV which is necessary for good monodispersity of
      nanoparticles solution. As compared with the QDs coated by SiO(2) (QDs@SiO(2)),
      the QDs-PDADMAC@SiO(2) nanoparticles have much stronger fluorescence, and their
      fluorescence stability could be obviously improved. Moreover, QDs-PDADMAC@SiO(2)
      exhibits good biological compatibility which promotes their application in
      cellular imaging.

PMID- 22365129
TI  - A dendrimer-based immunosensor for improved capture and detection of tumor
      necrosis factor-alpha cytokine.
AB  - A dendrimer-based sandwich type enzyme-linked immunosorbent assay (ELISA) was
      developed for the improved detection of recombinant human tumor necrosis factor
      alpha (TNF-alpha) for early diagnosis of perinatal diseases. Hydroxyl-terminated
      generation four poly(amidoamine) dendrimer (G4-OH) was used for the development
      of a solid phase bio-sensing platform. The surface of the ELISA plate was
      modified with polyethylene-glycol (PEG) and thiol-functionalized G4-OH was
      immobilized on the PEG-functionalized plate. A capture antibody was oxidized and
      covalently immobilized onto the dendrimer-modified ELISA plate, which provides
      favorable orientation for the antigen binding sites toward the analyte. The
      dendrimer-modified plate showed enhanced sensitivity, and the detection limit for
      TNF-alpha was found to be 0.48 pg mL(-1), which is significantly better than the
      commercially available ELISA kit. The selectivity of the dendrimer-modified ELISA
      plate was further evaluated with a mixture of cytokines, which showed results for
      similar to that of TNF-alpha alone. The modified plate provides a greater
      opportunity for the detection of a wide range of cytokines and biomarkers.

PMID- 22365130
TI  - Chromogenic platform based on recombinant Drosophila melanogaster
      acetylcholinesterase for visible unidirectional assay of organophosphate and
      carbamate insecticide residues.
AB  - In this study we propose a chromogenic platform for rapid analysis of
      organophosphate (OP) and carbamate (CM) insecticide residues, based on
      recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and
      indoxyl acetate as substrate. The visible chromogenic strip had the advantages
      identical to those of commonly used lateral flow assays (LFAs) with utmost
      simplicity in sample loading and result observation. After optimization,
      depending on the color intensity (CI) values, the well-established assay has the
      capabilities of both qualitative measurement via naked eyes and quantitative
      analysis by colorimetric reader with the desirable IC(50) values against the
      tested six insecticides (0.06 MUg mL(-1) of carbofuran, 0.28 MUg mL(-1) of
      methomyl, 0.03 MUg mL(-1) of dichlorvos, 31.6 MUg mL(-1) of methamidophos, 2.0
      MUg mL(-1) of monocrotophos, 6.3 MUg mL(-1) of omethoate). Acceptable matrix
      effects and satisfactory detection performance were confirmed by in-parallel LC
      MS/MS analysis in different vegetable varieties at various spiked levels of 10(
      3) to 10(1) MUg g(-1). Overall, the testified suitability and applicability of
      this novel platform meet the requirements for practical use in food safety
      management and environmental monitoring, especially in the developing world.

PMID- 22365131
TI  - Determination of non-steroidal anti-inflammatory drugs in water samples by solid
      phase microextraction based sol-gel technique using poly(ethylene glycol) grafted
      multi-walled carbon nanotubes coated fiber.
AB  - In this study, poly(ethylene glycol) (PEG) grafted multi-walled carbon nanotubes
      (PEG-g-MWCNTs) were synthesized by the covalent functionalization of MWCNTs with
      hydroxyl-terminated PEG chains. PEG-g-MWCNTs was used as a novel stationary phase
      to prepare the sol-gel solid-phase microextraction (SPME) fiber in combination
      with gas chromatography-flame ionization detector (GC-FID) for the determination
      of ibuprofen, naproxen and diclofenac in real water samples. Some parameters
      which influencing the extraction efficiency were such as desorption temperature
      and time, extraction temperature and time, pH, salt effect and stirring speed
      that were investigated and optimized. Under the optimal conditions, the method
      detection limits (S/N=3) were in the range of 0.007-0.03 ng mL(-1) and the limits
      of quantification (S/N=10) between 0.05 and 0.07 ng mL(-1). The relative standard
      deviations (RSDs) for one fiber (repeatability) (n=5) were obtained from 5.9 up
      to 8.1% and between fibers or batch to batch (n=3) (reproducibility) in the range
      of 7.2-9.1%. The developed method was successfully applied to real water samples
      while the relative recovery percentages obtained for the spiked water samples at
      0.2 ng mL(-1) were from 84 to 107%.

PMID- 22365132
TI  - Prediction of liquid chromatographic retention for differentiation of structural
      isomers.
AB  - A liquid chromatography (LC) retention time prediction software, ACD/ChromGenius,
      was employed to calculate retention times for structural isomers, which cannot be
      differentiated by accurate mass measurement techniques alone. For 486 drug
      compounds included in an in-house database for urine drug screening by liquid
      chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS), a
      retention time knowledge base was created with the software. ACD/ChromGenius
      calculated retention times for compounds based on the drawn molecular structure
      and given chromatographic parameters. The ability of the software for compound
      identification was evaluated by calculating the retention order of the 118
      isomers, in 50 isomer groups of 2-5 compounds each, included in the database.
      ACD/ChromGenius predicted the correct elution order for 68% (34) of isomer
      groups. Of the 16 groups for which the isomer elution order was incorrectly
      calculated, two were diastereomer pairs and thus difficult to distinguish using
      the software. Correlation between the calculated and experimental retention times
      in the knowledge base tested was moderate, r(2)=0.8533. The mean and median
      absolute errors were 1.12 min, and 0.84 min, respectively, and the standard
      deviation was 1.04 min. The information generated by ACD/ChromGenius, together
      with other in silico methods employing accurate mass data, makes the
      identification of substances more reliable. This study demonstrates an approach
      for tentatively identifying compounds in a large target database without a need
      for primary reference standards.

PMID- 22365133
TI  - Nuts and seed: a natural yet dangerous foreign body.
AB  - RATIONALE AND AIM: This paper has the object to present the impact of nuts' and
      seeds' injuries withdrawing data from the Susy Safe registry, highlighting that
      as for other foreign bodies the main item efficiently and substantially
      susceptible to changes to decrease the accidents' rates is the education of
      adults and children, that can be shared with parents both from pediatricians and
      general practitioners. Indeed labeling and age related warnings have also a
      fundamental relevance in prevention. METHODS: The present study draws its data
      from the Susy Safe registry. Details on injuries are entered in the Susy Safe Web
      registry through a standardized case report form, that includes information
      regarding: children age and gender, features of the object, circumstances of
      injury (presence of parents and activity) and hospitalization's details (lasting,
      complications and removal details). Cases are prospectively collected using the
      Susy Safe system from 06/2005; moreover, also information regarding past
      consecutive cases available in each centre adhering to the project have been
      entered in the Susy Safe registry. RESULTS: Nuts and seeds are one of the most
      common food item retrieved in foreign bodies injuries in children. In Susy Safe
      registry they represent the 38% in food group, and almost the 10% in general
      cases. Trachea, bronchi and lungs were the main location of FB's retrieval,
      showing an incidence of 68%. Hospitalization occurred in 83% of cases, showing
      the major frequency for foreign bodies located in trachea. This location was also
      the principal site of complications, with a frequency of 68%. There were no
      significant associations between these outcomes and the age class of the
      children. The most common complications seen (22.4%) was bronchitis, followed by
      pneumonia (19.7%). Adult presence was recorded as positive in 71.2% of cases,
      showing an association (p value 0.009) between the adult supervision and the
      hospitalization outcome. On the contrary there was a non significant association
      between adult presence and the occurrence of complications. In 80.7% of cases,
      the incident happened while the child was eating. Among those cases, 88.6%
      interested trachea, lungs and bronchi. CONCLUSIONS: Food-related aspiration
      injuries are common events for young children, particularly under 4 years of age,
      and may lead to severe complication. There is a need to study in more depth
      specific characteristics of foreign bodies associated with increased hazard, such
      as size, shape, hardness or firmness, lubricity, pliability and elasticity, in
      order to better identify risky foods, and more precisely described the
      pathogenetic pathway. Parents are not adequately conscious and aware toward this
      risk; therefore, the number and severity of the injuries could be reduced by
      educating parents and children. Information about food safety should be included
      in all visits to pediatricians in order to make parents able to understand,
      select, and identify key characteristics of hazardous foods and better control
      the hazard level of various foods. Finally, preventive measures including warning
      labels on high-risk foods could be implemented.

PMID- 22365134
TI  - Cluster sampling with referral to improve the efficiency of estimating unmet
      needs among pregnant and postpartum women after disasters.
AB  - INTRODUCTION AND BACKGROUND: Women of reproductive age, in particular women who
      are pregnant or fewer than 6 months postpartum, are uniquely vulnerable to the
      effects of natural disasters, which may create stressors for caregivers, limit
      access to prenatal/postpartum care, or interrupt contraception. Traditional
      approaches (e.g., newborn records, community surveys) to survey women of
      reproductive age about unmet needs may not be practical after disasters. Finding
      pregnant or postpartum women is especially challenging because fewer than 5% of
      women of reproductive age are pregnant or postpartum at any time. METHODS: From
      2009 to 2011, we conducted three pilots of a sampling strategy that aimed to
      increase the proportion of pregnant and postpartum women of reproductive age who
      were included in postdisaster reproductive health assessments in Johnston County,
      North Carolina, after tornadoes, Cobb/Douglas Counties, Georgia, after flooding,
      and Bertie County, North Carolina, after hurricane-related flooding. RESULTS:
      Using this method, the percentage of pregnant and postpartum women interviewed in
      each pilot increased from 0.06% to 21%, 8% to 19%, and 9% to 17%, respectively.
      CONCLUSION AND DISCUSSION: Two-stage cluster sampling with referral can be used
      to increase the proportion of pregnant and postpartum women included in a
      postdisaster assessment. This strategy may be a promising way to assess unmet
      needs of pregnant and postpartum women in disaster-affected communities.

PMID- 22365135
TI  - Circulating 25-hydroxyvitamin D levels in relation to blood pressure parameters
      and hypertension in the Shanghai Women's and Men's Health Studies.
AB  - Little is known about the association of circulating 25-hydroxyvitamin D
      (25(OH)D) and blood pressure (BP) parameters, including systolic and diastolic
      BP, pulse pressure (PP), mean arterial pressure (MAP) and hypertension in non
      Western populations that have not yet been exposed to foods fortified with
      vitamins and seldom use vitamin D supplements. A cross-sectional analysis of
      plasma 25(OH)D levels in association with BP measures was performed for 1460
      participants (1055 women and 405 men, aged 40-74 years) of two large cohort
      studies in Shanghai. Multivariable linear and logistic regressions were
      conducted. Overall, the prevalence of vitamin D deficiency was 55.8 % using
      National Health and Nutrition Examination Survey, USA criteria and 29.9 % using
      WHO criteria. The median plasma 25(OH)D level in the population was 38.0 nmol/l
      for men and 33.6 nmol/l for women (P < 0.01) among participants who were not on
      antihypertensive drugs. Among men, BP parameters (systolic BP, diastolic BP and
      MAP) were significantly and inversely associated with higher quintiles of 25(OH)D
      compared with the lowest quintile (P trend < 0.05 for all). Vitamin D non
      deficient status (WHO criteria) was inversely associated with hypertension
      (ORadjusted = 0.29; 95 % CI 0.10, 0.82). An inverse association was also found
      between hypertension and the highest quintile of 25(OH)D (ORadjusted = 0.16; 95 %
      CI 0.04, 0.65 for >= 50.6 nmol/l; P trend = 0.02). Among women, no significant
      associations were found for BP parameters and hypertension. The present study
      shows that vitamin D deficiency is common among adults in urban China.
      Circulating 25(OH)D levels were inversely related to the levels of individual BP
      parameters and hypertension among middle-aged and elderly men but not among
      women. More research is needed to investigate the potential sex differential
      associations.

PMID- 22365136
TI  - Characterizing Mycobacterium tuberculosis isolates from Karachi, Pakistan: drug
      resistance and genotypes.
AB  - OBJECTIVES: To study the prevalence, risk factors, and genotypes of drug
      resistant Mycobacterium tuberculosis in Karachi. METHODS: Pulmonary tuberculosis
      (TB) patients were recruited in a cross-sectional study (2006-2009). Drug
      susceptibility testing was performed for culture-positive cases (n=1004). Factors
      associated with drug resistance were evaluated using logistic regression
      analysis. Strains were typed using spoligotyping and mycobacterial interspersed
      repetitive units-variable number tandem repeat (MIRU-VNTR). The associations of
      genotype and drug resistance were explored using the Chi-square test. RESULTS:
      Resistance rates - new and previously treated - were as follows: multidrug
      resistant (MDR)-TB, 2.4% and 13.9%, respectively; rifampin (RIF) monoresistance,
      0.1% and 0.6%, respectively; any isoniazid (INH) resistance, 8.9% and 28.5%,
      respectively; and INH monoresistance, 3.0% and 6.3%, respectively. Prior TB
      treatment was a risk factor for MDR-TB (adjusted odds ratio (AOR) 6.8, 95%
      confidence interval (CI) 3.5-13.1) and INH monoresistance (AOR 2.4, 95% CI 1.1
      5.2). Additional risk factors included low socioeconomic status for INH
      monoresistance (AOR 3.3, 95% CI 1.7-6.5), and belonging to Balouchi (AOR 9.2, 95%
      CI 2.5-33.4), Sindhi (AOR 4.1, 95% CI 1.2-13.5), or Pakhtun (AOR 3.4, 95% CI 1.0
      11.2) ethnicity for MDR-TB. Although Central Asian strain (55.6%) was the most
      prevalent genotype, MDR-TB was significantly associated with Haarlem (H)
      genogroup (crude OR 9.2, 95% CI 3.6-23.8). CONCLUSIONS: An MDR-TB rate of 2.4% is
      reported in new patients. Low RIF monoresistance supports the use of RIF as a
      marker for MDR-TB in this population. The need to strengthen TB care in the
      identified at-risk groups is emphasized. Based on INH resistance rates, a review
      of national treatment/prevention regimens relying on INH is suggested.

PMID- 22365137
TI  - Odontogenic maxillofacial space infections at a tertiary care center in North
      India: a five-year retrospective study.
AB  - OBJECTIVE: Odontogenic infections contribute to a significant proportion of
      maxillofacial space infections (MSI) across the world. MSI can cause several life
      threatening complications despite skillful management. The objective of this
      study was to review the clinical characteristics, management, and outcome of
      odontogenic MSI treated at a tertiary care center, and to identify the factors
      predisposing to life-threatening complications. METHODS: A retrospective chart
      review of all patients treated for MSI from January 2006 to December 2010 at the
      Christian Medical College Hospital in Ludhiana, North India, was conducted.
      RESULTS: Out of 137 patients identified, 66.4% were men. Mean patient age was 40
      years, and 24.1% of the patients were diabetic. The most common origin was pulpal
      (70.8%), the most common space involved was the submandibular space, and the most
      common teeth responsible were the lower third molars. Twenty patients (14.6%)
      developed complications. Diabetes, multiple space involvement, and a total
      leukocyte count of >=15*10(9)/l were associated with complications. CONCLUSIONS:
      Patients with MSI who present with multiple space involvement, a high leukocyte
      count, and those with diabetes are at higher risk of developing life-threatening
      complications and need to be closely monitored.

PMID- 22365138
TI  - Particulate matter (PM10) exposure induces endothelial dysfunction and
      inflammation in rat brain.
AB  - Epidemiological studies suggest that particulate matter (PM(10)) inhalation was
      associated with adverse effects on brain-related health, however, existing
      experimental data lacked relevant evidences. In this study, we treated Wistar
      rats with PM(10) at different concentrations (0.3, 1, 3 and 10 mg/kg body weight
      (bw)), and investigated endothelial dysfunction and inflammatory responses in the
      brain. The results indicate that mild pathological abnormal occurred after 15-day
      exposure (five times with 3 days each), followed by the changes of endothelial
      mediators (ET-1 and eNOS) and inflammatory markers (IL-1beta, TNF-alpha, COX-2,
      iNOS and ICAM-1). Also, the sample up-regulated bax/bcl-2 ratio and p53
      expression, and induced neuronal apoptosis. It implicates that PM(10) exerted
      injuries to mammals' brain, and the mechanisms might be involved in endothelial
      dysfunction and inflammatory responses.

PMID- 22365139
TI  - Electrokinetic-enhanced bioaugmentation for remediation of chlorinated solvents
      contaminated clay.
AB  - Successful bioremediation of contaminated soils is controlled by the ability to
      deliver bioremediation additives, such as bacteria and/or nutrients, to the
      contaminated zone. Because hydraulic advection is not practical for delivery in
      clays, electrokinetic (EK) injection is an alternative for efficient and uniform
      delivery of bioremediation additive into low-permeability soil and heterogeneous
      deposits. EK-enhanced bioaugmentation for remediation of clays contaminated with
      chlorinated solvents is evaluated. Dehalococcoides (Dhc) bacterial strain and
      lactate ions are uniformly injected in contaminated clay and complete
      dechlorination of chlorinated ethene is observed in laboratory experiments. The
      injected bacteria can survive, grow, and promote effective dechlorination under
      EK conditions and after EK application. The distribution of Dhc within the clay
      suggests that electrokinetic transport of Dhc is primarily driven by
      electroosmosis. In addition to biodegradation due to bioaugmentation of Dhc, an
      EK-driven transport of chlorinated ethenes is observed in the clay, which
      accelerates cleanup of chlorinated ethenes from the anode side. Compared with
      conventional advection-based delivery, EK injection is significantly more
      effective for establishing microbial reductive dechlorination capacity in low
      permeability soils.

PMID- 22365140
TI  - Green synthesis of nanosilver as a sensor for detection of hydrogen peroxide in
      water.
AB  - Present "green" synthesis is an efficient, easy-going, fast, renewable,
      inexpensive, eco-friendly and non-toxic approach for nanosilver formation, which
      offers numerous benefits over physiochemical approaches. The X-ray diffraction
      (XRD) pattern suggests the formation and crystallinity of nanosilver. The average
      particle size of silver nanoparticles was 8.25+/-1.37 nm as confirmed by
      transmission electron microscopy (TEM). The UV-vis absorption spectrum shows a
      characteristic absorption peak of silver nanoparticles at 410 nm. FTIR confirms
      Azadirachtin as reducing and stabilizing agent for nanosilver formation. In
      addition, the nanosilver modified electrode (Ag/GC) exhibited an excellent
      electro-catalytic activity toward the reduction of hydrogen peroxide (H(2)O(2)).
      The produced nanosilver is stable and comparable in size. These silver
      nanoparticles show potential applications in the field of sensors, catalysis,
      fuel cells and nanodevices.

PMID- 22365141
TI  - Management of metal chlorides in high temperature processes--application to the
      nuclear wastes treatment.
AB  - Thermal processes are now the benchmark for the destruction of some waste whose
      toxicity requires special attention and management. Over many years the
      Commissariat a l'Energie Atomique (French atomic energy commission) has developed
      technologies to process radioactive waste containing many metals together with
      chlorine, and thus with a major risk of producing volatile chlorides with
      potentially catastrophic effects on plant facilities. To mitigate these
      difficulties in an incineration process for radioactive waste contaminated by
      plutonium (IRIS), the CEA has investigated the processes by which potentially
      hazardous compounds are produced in order to eliminate them or prevent their
      formation. The studies have led to propose a phosphate-based stabilization
      technique thanks to an addition of phosphorus in the waste. Through a reaction
      occurring in gas phase, the metals are stabilized under a phosphate form when the
      formation of volatiles chlorides is avoided. While this technique has
      substantially improved process maintenance and security, it has revealed other
      difficulties related to potentially large phosphate deposits capable to cause
      unacceptable pressure drops detrimental to the gas flow conditions. This article
      describes the results of recent studies seeking to prevent the formation of
      volatile chlorides and phosphate deposits liable to obstruct the system flow
      lines.

PMID- 22365142
TI  - Multivariate factorial analysis to design a robust batch leaching test to assess
      the volcanic ash geochemical hazard.
AB  - A method to obtain robust information on short term leaching behaviour of
      volcanic ashes has been developed independently on the sample age. A mixed
      factorial design (MFD) was employed as a multivariate strategy for the evaluation
      of the effects of selected control factors and their interactions (amount of
      sample (A), contact time (B), and liquid to solid ratio or L/S (C)) on the
      leaching process of selected metals (Na, K, Mg, Ca, Si, Al, V, Mn, Fe, and Co)
      and anions (Cl(-) and SO(4)(2-)). Box plots of the data acquired were used to
      evaluate the reproducibility achieved at different experimental conditions. Both
      the amount of sample (A) and leaching time (B) had a significant effect on the
      element stripping whereas the L/S ratio influenced only few elements. The lowest
      dispersion values have been observed when 1.0 g was leached with an L/S ratio
      equal to 10, shaking during 4 h. The entire method is completed within few hours,
      and it is simple, feasible and reliable in laboratory conditions.

PMID- 22365143
TI  - An efficient ultrasound assisted approach for the impregnation of room
      temperature ionic liquid onto Dowex 1*8 resin matrix and its application toward
      the enhanced adsorption of chromium (VI).
AB  - The work discussed in this paper is based on the utilization of ultrasound in
      conjunction with an ionic liquid (Aliquat 336) impregnated Dowex 1*8 resin for
      the effective adsorption of chromium. Ionic liquids are known for their
      selectivity toward metal extraction and ultrasonic medium offers efficient energy
      transfer for impregnating the ionic liquid in the resin matrix. The molecular
      interaction between the ionic liquid impregnated resin and chromium was studied
      through various physicochemical and spectroscopic techniques. The influence of
      various analytical parameters on the adsorption of Cr(VI) such as pH, adsorbent
      dosage, temperature and interference of foreign ions was studied in detail.
      Chromium (VI) was quantitatively adsorbed in the pH range of 3.5-4, with a high
      adsorption capacity of 230.9 mg g(-1) in conformity with the Langmuir isotherm
      model. The study of thermodynamic parameters showed that the adsorption process
      is exothermic and spontaneous. The adsorbent could be regenerated using 1 mol L(
      1) HCl-0.28 mol L(-1) ascorbic acid mixture. Chromium could be effectively
      detoxified from an industrial effluent and finally the developed method was
      validated with the analysis of a certified reference material (BCR-715). The
      obtained results indicated that the ultrasonic assisted impregnation of the room
      temperature ionic liquid significantly enhances and improves the removal
      efficiency of Cr(VI).

PMID- 22365144
TI  - Perturbations of the actin cytoskeleton activate a Dictyostelium STAT signalling
      pathway.
AB  - The Dictyostelium transcription factor STATc is tyrosine phosphorylated and
      accumulates in the nucleus when cells are exposed either to hyper-osmotic stress
      or to the prestalk-inducing polyketide DIF-1. In the case of stress STAT
      activation is mediated by regulated dephosphorylation; whereby two serine
      residues on PTP3, the tyrosine phosphatase that de-activates STATc, become
      phosphorylated after exposure to stress so inhibiting enzymatic activity. We now
      show that the more highly regulated of the two PTP3 serine residues, S747, is
      also phosphorylated in response to DIF-1, suggesting a common activation
      mechanism. Hyper-osmotic stress causes a re-distribution of F-actin to the
      cortex, cell rounding and shrinkage and we show that DIF-1 induces a similar but
      transient F-actin re-distribution and rounding response. We also find that two
      mechanistically distinct inhibitors of actin polymerization, latrunculin A and
      cytochalasin A induce phosphorylation at S747 of PTP3 and activate STATc. We
      suggest that PTP3 phosphorylation, and consequent STATc activation, are regulated
      by changes in F-actin polymerization status during stress and DIF-induced
      cytoskeletal remodelling.

PMID- 22365145
TI  - Effects of cerivastatin on adrenergic pathways, hypertrophic growth and TGFbeta
      expression in adult ventricular cardiomyocytes.
AB  - The effects of statin treatment in the setting of heart failure have already been
      shown. Nevertheless, there is little knowledge about its influence on adrenergic
      pathways in cardiomyocytes. Therefore, this study investigated the impact of
      cerivastatin on adrenoceptor-mediated signalling pathways in isolated adult
      ventricular cardiomyocytes. It focused on two endpoints: hypertrophic growth and
      TGFbeta expression. Cultured cardiomyocytes were used to study rac activation
      (analysed by its translocation into the membrane fraction), ROS formation
      (H(2)DCF fluorescence) and hypertrophic growth ((14)C-phenylalanine
      incorporation). Alpha- and beta-adrenoceptor stimulation showed significant
      differences regarding rac activation, ROS formation, and p38 MAP kinase
      activation. Both alpha- and beta-adrenoceptor stimulation induced TGFbeta
      expression. Upon activation of alpha-adrenergic signalling - although ROS
      formation was not influenced by cerivastatin - TGFbeta expression decreased.
      Following beta stimulation, TGFbeta expression as well as rac and p38 MAP kinase
      activation were reduced after pre-treatment with cerivastatin. Statin treatment
      did not show any influence on hypertrophic growth. In summary, this study clearly
      demonstrates the ability of adrenoceptor stimulation to increase TGFbeta
      expression. One component of the beneficial effects of statin therapy on heart
      failure might therefore be due to a dominant reduction and inhibition of TGFbeta,
      which is involved in many pathophysiological processes in cardiomyocytes.

PMID- 22365146
TI  - Regulation of cathepsins S and L by cystatin F during maturation of dendritic
      cells.
AB  - In dendritic cells (DCs) cysteine cathepsins play a key role in antigen
      processing, invariant chain (Ii) cleavage and regulation of cell adhesion after
      maturation stimuli. Cystatin F, a cysteine protease inhibitor, is present in DCs
      in endosomal/lysosomal vesicles and thus has a potential to modulate cathepsin
      activity. In immature DCs cystatin F colocalizes with cathepsin S. After
      induction of DC maturation however, it is translocated into lysosomes and
      colocalizes with cathepsin L. The inhibitory potential of cystatin F depends on
      the properties of the monomer. We showed that the full-length monomeric cystatin
      F was a 12-fold stronger inhibitor of cathepsin S than the N-terminally processed
      cystatin F, whereas no significant difference in inhibition was observed for
      cathepsins L, H and X. Therefore, the role of cystatin F in regulating the main
      cathepsin S function in DCs, i.e. the processing of Ii, may depend on the form of
      the monomer present in endosomal/lysosomal vesicles. On the other hand, intact
      and truncated monomeric cystatin F are both potent inhibitors of cathepsin L and
      it is likely that cystatin F could regulate its activity in maturing, adherent
      DCs, controlling the processing of procathepsin X, which promotes cell adhesion
      via activation of Mac-1 (CD11b/CD18) integrin receptor.

PMID- 22365147
TI  - Cytokines and inflammation.

PMID- 22365149
TI  - Decreased glutathione levels predict loss of brain volume in children and
      adolescents with first-episode psychosis in a two-year longitudinal study.
AB  - Progressive loss of cortical gray matter (GM), as measured by magnetic resonance
      imaging, has been described early in the course of first-episode psychosis. This
      study aims to assess the relationship between oxidative balance and progression
      of cortical GM changes in a multicenter sample of first-episode early-onset
      psychosis (EOP) patients from baseline to two-year follow-up. A total of 48
      patients (13 females, mean age 15.9+/-1.5 years) and 56 age- and gender-matched
      healthy controls (19 females, 15.3+/-1.5 years) were assessed. Magnetic resonance
      imaging (MRI) scans performed both at the time of the first psychotic episode and
      2 years later were used for volumetric measurements of left and right gray matter
      regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal
      fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In
      patients, after controlling for possible confounding variables, lower baseline
      GSH levels were significantly associated with greater volume decrease in left
      frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620,
      p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal
      (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI:
      0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total
      CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not
      show significant associations between brain volume changes and GSH levels. GSH
      deficit during the first psychotic episode was related to greater loss of
      cortical GM two years later in patients with first-episode EOP, suggesting that
      oxidative damage may contribute to the progressive loss of cortical GM found in
      patients with first-episode psychosis.

PMID- 22365148
TI  - Cortical gyrification in velo-cardio-facial (22q11.2 deletion) syndrome: a
      longitudinal study.
AB  - INTRODUCTION: Velo-cardio-facial syndrome (VCFS) has been identified as an
      important risk factor for psychoses, with up to 32% of individuals with VCFS
      developing a psychotic illness. Individuals with VCFS thus form a unique group to
      identify and explore early symptoms and biological correlates of psychosis. In
      this study, we examined if cortical gyrification pattern, i.e. gyrification index
      (GI) can be a potential neurobiological marker for psychosis. METHOD: GIs of 91
      individuals with VCFS were compared with 29 siblings and 54 controls. Further, 58
      participants with VCFS, 21 siblings and 18 normal controls were followed up after
      3 years and longitudinal changes in GI were compared. Additionally, we also
      correlated longitudinal changes in GI in individuals with VCFS with prodromal
      symptoms of psychosis on the Scale of Prodromal Symptoms (SOPS). RESULT:
      Individuals with VCFS had significantly lower GIs as compared to their siblings
      and normal controls. Longitudinal examination of GI did not reveal any
      significant group-time interactions between the three groups. Further,
      longitudinal change in GI scores in the VCFS group was negatively correlated with
      positive prodromal symptoms, with the left occipital region reaching statistical
      significance. CONCLUSION: The study confirms previous reports that individuals
      with VCFS have reduced cortical folding as compared to normal controls. However
      over a period of three years, there is no difference in the rate of change of GI
      among both individuals with VCFS and normal controls. Finally, our results
      suggest that neuroanatomical alterations in areas underlying visual processing
      may be an early marker for psychosis.

PMID- 22365150
TI  - Use of a multiethnic approach to identify rheumatoid- arthritis-susceptibility
      loci, 1p36 and 17q12.
AB  - We have previously shown that rheumatoid arthritis (RA) risk alleles overlap
      between different ethnic groups. Here, we utilize a multiethnic approach to show
      that we can effectively discover RA risk alleles. Thirteen putatively associated
      SNPs that had not yet exceeded genome-wide significance (p < 5 * 10(-8)) in our
      previous RA genome-wide association study (GWAS) were analyzed in independent
      sample sets consisting of 4,366 cases and 17,765 controls of European, African
      American, and East Asian ancestry. Additionally, we conducted an overall
      association test across all 65,833 samples (a GWAS meta-analysis plus the
      replication samples). Of the 13 SNPs investigated, four were significantly below
      the study-wide Bonferroni corrected p value threshold (p < 0.0038) in the
      replication samples. Two SNPs (rs3890745 at the 1p36 locus [p = 2.3 * 10(-12)]
      and rs2872507 at the 17q12 locus [p = 1.7 * 10(-9)]) surpassed genome-wide
      significance in all 16,659 RA cases and 49,174 controls combined. We used
      available GWAS data to fine map these two loci in Europeans and East Asians, and
      we found that the same allele conferred risk in both ethnic groups. A series of
      bioinformatic analyses identified TNFRSF14-MMEL1 at the 1p36 locus and IKZF3
      ORMDL3-GSDMB at the 17q12 locus as the genes most likely associated with RA.
      These findings demonstrate empirically that a multiethnic approach is an
      effective strategy for discovering RA risk loci, and they suggest that combining
      GWASs across ethnic groups represents an efficient strategy for gaining
      statistical power.

PMID- 22365153
TI  - Self-reporting of height and weight: valid and reliable identification of
      malnutrition in preoperative patients.
AB  - BACKGROUND: Preoperative screening for malnutrition has become mandatory in The
      Netherlands. A sensitive method to diagnose malnutrition would save time and
      improve effectiveness. METHODS: A prospective cross-sectional study of 488 adult
      elective preoperative outpatients was performed. The accuracy of self-reported
      height and weight was compared with measured data and 3 commonly used
      malnutrition screening tools. Interobserver agreement was calculated by the
      intraclass correlation coefficient, studied in Bland and Altman plots, and
      analyzed by using Cohen's kappa statistic. Accuracy was expressed in sensitivity,
      specificity, and false-negative rates. RESULTS: Differences between self-reported
      and measured data were significant, but clinically irrelevant, because only 1
      patient was falsely identified as well nourished. Intraclass correlation
      coefficient for height, weight, and body mass index was high (.97-.99). Bland
      Altman plots showed that the mean +/- standard deviation differences and 95%
      limits of agreement between both methods were as follows: height, .0096 m (+/
      .0262, -.0417 to +.0609 m); weight, -1.28 kg (+/-2.29, -5.76 to +3.20 kg); body
      mass index, -.72 kg/m(2) (+/-1.11, -2.92 to +1.46 kg/m(2)). The kappa coefficient
      was .84 (95% confidence interval, .75-.94). Sensitivity was .97 and specificity
      was .98. Sensitivity and false-negative rates of self-reported data were better
      overall compared with the screening tools. CONCLUSIONS: Self-reported data
      provide highly sensitive information to diagnose malnutrition in preoperative
      outpatients.

PMID- 22365154
TI  - Tuberculosis control in a highly endemic indigenous community in Brazil.
AB  - In Latin America, indigenous populations have high rates of non-completion of TB
      treatment and case fatality and have been defined as a priority group for
      investments. To evaluate TB control, a retrospective cohort study was performed
      to identify factors predictive of non-completion of treatment and mortality in an
      indigenous and non-indigenous population between 2002 and 2008 in Dourados,
      Brazil. A 90% reduction in non-completion of TB treatment was observed in the
      indigenous population after DOTS (directly observed treatment, short course)
      implementation (20% vs 2%). In the non-indigenous population, the number of
      patients not completing TB treatment continued to increase. Non-indigenous TB
      patients had 4.5 times higher mortality than indigenous TB patients (9% vs 2%).
      In multivariate analysis, non-indigenous race [odds ratio (OR) 2.33, 95% CI 1.32
      4.10] was associated with non-completion of TB treatment, and HIV-positive status
      (OR 5.58, 95% CI 2.38-13.07) was associated with mortality. Implementation of
      DOTS in the indigenous populations in Dourados showed a significant reduction in
      non-completion of TB treatment. Nevertheless, a high rate of TB in children and
      young adults indicates the continuous transmission and maintenance of the
      epidemic in this community. Among the non-indigenous population, the TB case
      fatality rate is closely linked to the HIV prevalence.

PMID- 22365151
TI  - The Basque paradigm: genetic evidence of a maternal continuity in the Franco
      Cantabrian region since pre-Neolithic times.
AB  - Different lines of evidence point to the resettlement of much of western and
      central Europe by populations from the Franco-Cantabrian region during the Late
      Glacial and Postglacial periods. In this context, the study of the genetic
      diversity of contemporary Basques, a population located at the epicenter of the
      Franco-Cantabrian region, is particularly useful because they speak a non-Indo
      European language that is considered to be a linguistic isolate. In contrast with
      genome-wide analysis and Y chromosome data, where the problem of poor time
      estimates remains, a new timescale has been established for the human mtDNA and
      makes this genome the most informative marker for studying European prehistory.
      Here, we aim to increase knowledge of the origins of the Basque people and, more
      generally, of the role of the Franco-Cantabrian refuge in the postglacial
      repopulation of Europe. We thus characterize the maternal ancestry of 908 Basque
      and non-Basque individuals from the Basque Country and immediate adjacent regions
      and, by sequencing 420 complete mtDNA genomes, we focused on haplogroup H. We
      identified six mtDNA haplogroups, H1j1, H1t1, H2a5a1, H1av1, H3c2a, and H1e1a1,
      which are autochthonous to the Franco-Cantabrian region and, more specifically,
      to Basque-speaking populations. We detected signals of the expansion of these
      haplogroups at ~4,000 years before present (YBP) and estimated their separation
      from the pan-European gene pool at ~8,000 YBP, antedating the Indo-European
      arrival to the region. Our results clearly support the hypothesis of a partial
      genetic continuity of contemporary Basques with the preceding
      Paleolithic/Mesolithic settlers of their homeland.

PMID- 22365155
TI  - Nicotine control: E-cigarettes, smoking and addiction.
AB  - BACKGROUND: Over the past year or so, electronic cigarettes, more commonly known
      as 'e-cigarettes', have achieved widespread visibility and growing popularity.
      These products, which deliver nicotine via an inhaled mist, have caused no small
      amount of controversy in public health circles, and their rise has been
      accompanied by energetic debate about their potential harms and benefits.
      METHODS: Interspersed with an analysis of current media coverage on e-cigarettes
      and the response of mainstream tobacco control and public health to these
      devices, this article examines the emergence of nicotine as both as an
      'addiction' and a treatment for addiction. RESULTS: We argue that by delivering
      nicotine in way that resembles the visual spectacle and bodily pleasures of
      smoking, but without the harms of combustible tobacco, e-cigarettes highlight the
      complex status of nicotine as both a poison and remedy in contemporary public
      health and tobacco control. CONCLUSION: In consequence, e-cigarettes jeopardize
      the carefully drawn distinctions between 'good' and 'bad' forms of nicotine.

PMID- 22365152
TI  - De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a
      family quartet affected by infantile epileptic encephalopathy and SUDEP.
AB  - Individuals with severe, sporadic disorders of infantile onset represent an
      important class of disease for which discovery of the underlying genetic
      architecture is not amenable to traditional genetic analysis. Full-genome
      sequencing of affected individuals and their parents provides a powerful
      alternative strategy for gene discovery. We performed whole-genome sequencing
      (WGS) on a family quartet containing an affected proband and her unaffected
      parents and sibling. The 15-year-old female proband had a severe epileptic
      encephalopathy consisting of early-onset seizures, features of autism,
      intellectual disability, ataxia, and sudden unexplained death in epilepsy. We
      discovered a de novo heterozygous missense mutation (c.5302A>G [p.Asn1768Asp]) in
      the voltage-gated sodium-channel gene SCN8A in the proband. This mutation alters
      an evolutionarily conserved residue in Nav1.6, one of the most abundant sodium
      channels in the brain. Analysis of the biophysical properties of the mutant
      channel demonstrated a dramatic increase in persistent sodium current, incomplete
      channel inactivation, and a depolarizing shift in the voltage dependence of
      steady-state fast inactivation. Current-clamp analysis in hippocampal neurons
      transfected with p.Asn1768Asp channels revealed increased spontaneous firing,
      paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency,
      consistent with a dominant gain-of-function phenotype in the heterozygous
      proband. This work identifies SCN8A as the fifth sodium-channel gene to be
      mutated in epilepsy and demonstrates the value of WGS for the identification of
      pathogenic mutations causing severe, sporadic neurological disorders.

PMID- 22365156
TI  - Cardio-renal syndromes: introduction.

PMID- 22365157
TI  - Cardio-renal syndrome: new perspective in diagnostics.
AB  - Chronic heart failure and chronic renal failure are at epidemic proportions.
      These patients have significantly altered cardiac, renal, and all-cause outcomes.
      Much of the current research has focused on treating these individual organs in
      isolation. Although there are positive data on outcomes with neurohormonal
      modulation, they, however, remain underused. At present, data lacks for novel
      treatment options, while evidence continues to point at significantly worsened
      prognosis. Current diagnostic tools that detect acute changes in renal function
      or renal injury appear retrospective, which often hinder meaningful diagnostic
      and therapeutic decisions. This review is aimed at exploring the importance of
      accurate assessment of renal function for the heart failure patient by providing
      a synopsis on cardio-renal physiology and establishing the possibility of novel
      approaches in bridging the divide.

PMID- 22365158
TI  - Cardio-renal syndrome type 1: epidemiology, pathophysiology, and treatment.
AB  - One third of heart failure admissions may be complicated by acute kidney injury,
      resulting in a three-fold increase in length of stay and a greater likelihood of
      rehospitalization. Cardio-Renal syndrome type 1 refers to acute decompensation of
      cardiac function leading to acute renal failure. It often complicates acute
      coronary syndrome and acute decompensated heart failure. Both components of the
      syndrome contribute to morbidity and mortality. The pathophysiology of renal
      dysfunction is complex. Reduced cardiac output, passive congestion of the
      kidneys, and increased intra-abdominal pressure may contribute to the disorder.
      The heart, kidneys, renin-angiotensin system, sympathetic nervous system, immune
      system, and vasculature interact through intricate feedback loops. An imbalance
      in this complex system often will cause deterioration in both cardiac and renal
      function. Appreciation of these interactions is crucial to understanding the
      overall burden of disease, as well as its natural history, risk factors,
      associated morbidity and mortality, and therapeutic implications.

PMID- 22365159
TI  - Cardio-renal syndrome type 2: epidemiology, pathophysiology, and treatment.
AB  - Cardiac and kidney disease are becoming increasingly more prevalent in the
      population, and may exist concurrently. One of the most important comorbidities
      in heart failure is renal dysfunction. The pathophysiology of cardio-renal
      syndromes is complicated, and has been divided into five categories. Cardio-Renal
      syndrome type 2 is described by chronic cardiac abnormalities resulting in
      impaired renal function. It is important to recognize this entity and to
      understand the pathophysiology underlying the cardiac and renal disorders to
      distinguish best treatment practices. The success in improved outcomes lies in
      optimization of heart failure therapies.

PMID- 22365160
TI  - Cardio-renal syndrome type 3: epidemiology, pathophysiology, and treatment.
AB  - A complex pathophysiology, cardio-renal syndrome (CRS), has been redefined in
      recent years. One subtype is acute renocardiac CRS, or CRS type 3. This syndrome
      is intended to comprise situations in which acute kidney injury (AKI) results in
      acute cardiac injury or dysfunction. The pathophysiology of CRS type 3 is not
      well understood. Existing evidence suggests a bidirectional link between these
      two organ systems. The mechanisms whereby AKI leads to cardiac dysfunction have
      been proposed to include two categories: direct effects of AKI on the heart, and
      effects of AKI on remote organ function with indirect effects on the heart. AKI
      has been shown to cause inflammation in experimental renal ischemic models, which
      then induced cytokine expression, leukocyte infiltration into the heart, cell
      death by apoptosis, and impaired cardiac function. Combined with this finding is
      the well-known significant physiological derangements, such as fluid and
      electrolyte imbalance and uremia, that underpin remote organ failure and finally
      affect cardiac function, which in turn causes further kidney injury. This vicious
      cycle is fundamental to cardio-renal syndromes. The high morbidity and mortality
      is likely a result of this adverse synergy. A standard definition and diagnostic
      criteria are important first steps to approach this syndrome. Results obtained
      from studies using a standard definition of AKI can lead us to the next step of
      early recognition, prevention, therapeutic intervention, and improved quality of
      care. Novel biomarkers and therapeutic interventions for primary and secondary
      disorders are being developed and tested. The hope is that improved outcomes will
      follow.

PMID- 22365161
TI  - Cardio-renal syndrome type 4: epidemiology, pathophysiology and treatment.
AB  - Cardiovascular diseases such as coronary artery disease, congestive heart
      failure, arrhythmia, and sudden cardiac death represent the leading causes of
      morbidity and mortality in patients with CKD, increasing sharply as patients
      approach end-stage renal disease. The pathogenesis includes a complex,
      bidirectional interaction between the heart and kidneys that encompasses
      traditional and nontraditional risk factors, and has been termed cardio-renal
      syndrome type 4. In this review, an overview of the epidemiology and scope of
      this problem is provided, some suggested mechanisms for the pathophysiology of
      this disorder are discussed, and some of the key treatment strategies are
      described, with particular focus on recent clinical trials, both negative and
      positive.

PMID- 22365162
TI  - Cardio-renal syndrome type 5: epidemiology, pathophysiology, and treatment.
AB  - The cardio-renal syndromes (CRS) recently were defined systematically as
      disorders of the heart or kidney whereby dysfunction of one organ leads to
      dysfunction of another. Five types of CRS are defined. The first four types
      describe acute or chronic cardio-renal or renocardiac syndromes. Type 5 CRS
      refers to secondary cardio-renal syndrome or cardio-renal involvement in systemic
      conditions. It is a clinical and pathophysiological entity to describe the
      concomitant presence of renal and cardiovascular dysfunction. Type 5 CRS can be
      acute or chronic and it does not strictly satisfy the definition of CRS. However,
      it encompasses many conditions in which combined heart and kidney dysfunction is
      observed. Because this entity has been described only recently there is limited
      information about the epidemiology, clinical course, and treatment of this
      condition.

PMID- 22365163
TI  - Role of iron deficiency and anemia in cardio-renal syndromes.
AB  - Chronic heart failure is a common disorder associated with unacceptably high
      mortality rates. Chronic renal disease and anemia are two important comorbidities
      that significantly influence morbidity and mortality in patients with chronic
      heart failure (CHF). Progress in CHF again may cause worsening of kidney function
      and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome
      has been suggested. Iron deficiency is part of the pathophysiology of anemia in
      both CHF and chronic kidney disease, which makes it an interesting target for
      treatment of anemia in cardio-renal anemia syndrome. Recently, studies have
      highlighted the potential clinical benefits of treating iron deficiency in
      patients with CHF, even if these patients are nonanemic. This article summarizes
      studies investigating the influence of iron deficiency with or without anemia in
      chronic kidney disease and CHF and gives an overview of preparations of
      intravenous iron currently available.

PMID- 22365164
TI  - Role of vitamin d receptor activators in cardio-renal syndromes.
AB  - The involvement of vitamin D deficiency in cardiovascular morbidity and mortality
      is attracting great interest. In patients with chronic kidney disease this
      association is stronger because vitamin D levels decrease as a result of renal
      progressive impairment. In chronic kidney disease secondary hyperparathyroidism
      commonly occurs in response to persistent hypocalcemia and hyperphosphatemia;
      moreover, parathyroid gland volume increases, vascular calcification is
      accelerated, and structural and functional modifications of the left ventricle
      are observed. These alterations entail both cardiac and renal involvement,
      resulting in cardio-renal syndrome. Recent studies concluded that vitamin D
      administration seems to have cardioprotective and renoprotective effects and
      improve peripheral vascular disease, vascular calcification, cardiac outcome, and
      blood pressure control. In clinical practice, therefore, the use of this hormone
      may play an important role in cardio-renal syndrome prevention.

PMID- 22365165
TI  - The role of inflammation in the cardio-renal syndrome: a focus on cytokines and
      inflammatory mediators.
AB  - Cardiovascular and kidney diseases are highly prevalent and frequently are seen
      in the same patient. This overlap between cardiac and kidney diseases, in part,
      relates to common etiologies such as diabetes and hypertension. However, there
      are important dynamic and bidirectional interactions between the cardiovascular
      system and kidneys that may explain the occurrence of organ dysfunction. In this
      regard, it is clear that inflammation plays an important role in the pathogenesis
      of both cardiovascular and renal diseases. Given the circulating nature of many
      inflammatory mediators (cytokines, immune cells), it is tempting to speculate
      that the immune system can act as a mediator of organ cross-talk and may be
      involved in the reciprocal dysfunction that is encountered commonly in cardio
      renal syndromes.

PMID- 22365166
TI  - Role of biomarkers in the diagnosis and management of cardio-renal syndromes.
AB  - The complex interaction between heart and kidney disease has been increasingly
      recognized over the recent years. Pathologies within these two organs frequently
      coexist and, due to organ cross-talk, dysfunction in one often leads to problems
      in the other. The classification of the various forms of cardio-renal syndrome
      has made these interactions clearer. To aid in the diagnosis, management and
      prognosis of these conditions, many novel cardiac and renal biomarkers have
      emerged to supplement traditional markers which have limited specificity and
      sensitivity. In this review we will summarize the literature on novel renal
      behind these and other biomarkers and discuss their potential relevance to the
      clinical scenarios of cardio-renal syndrome.

PMID- 22365167
TI  - Role of bioimpedance vectorial analysis in cardio-renal syndromes.
AB  - The cardio-renal syndromes (CRS) are the result of complex bidirectional organ
      cross-talk between the heart and kidney, with tremendous overlap of diseases such
      as coronary heart disease, heart failure (HF), and renal dysfunction in the same
      patient. Volume overload plays an important role in the pathophysiology of CRS.
      The appropriate treatment of overhydration, particularly in HF and in chronic
      kidney disease, has been associated with improved outcomes and blood pressure
      control. Clinical examination alone is often insufficient for accurate assessment
      of volume status because significant volume overload can exist even in the
      absence of peripheral or pulmonary edema on physical examination or radiography.
      Bioelectrical impedance techniques increasingly are being used in the management
      of patients with HF and those on chronic dialysis. These methods provide more
      objective estimates of volume status in such patients. Used in conjunction with
      standard clinical assessment and biomarkers such as the natriuretic peptides,
      bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration
      therapies and subsequently restoring such patients to a euvolemic or optivolemic
      state. In this article, we review the use of these techniques in CRS.

PMID- 22365168
TI  - Extracorporeal ultrafiltration in heart failure and cardio-renal syndromes.
AB  - Acute decompensated heart failure and fluid overload are the most common causes
      of hospitalization in heart failure patients and they often contribute to disease
      progression. Initial treatment encompasses intravenous diuretics, although there
      might be a percentage of patients refractory to this pharmacologic approach. New
      technologies have been developed to perform extracorporeal ultrafiltration in
      fluid-overloaded patients. Newer simplified devices permit ultrafiltration to be
      performed with peripheral venous access and low blood flows, making
      ultrafiltration feasible at most hospitals and acute care settings.
      Extracorporeal ultrafiltration then is prescribed and conducted by specialized
      teams and fluid removal is planned to restore a status of hydration close to
      normal. Recent clinical trials, and European and North American practice
      guidelines, suggest that ultrafiltration is reasonable for patients with
      refractory congestion not responding to medical therapy and assigned to this
      recommendation a class IIa, level of evidence B. It seems that a close
      collaboration between nephrologists and cardiologists may be the key for a
      collaborative therapeutic effort in heart failure patients. Further studies
      suggest that wearable technologies might become available soon to treat patients
      in ambulatory and de-hospitalized settings. These new technologies may help to
      cope with the increasing demand for care of chronic heart failure patients.

PMID- 22365169
TI  - Fluid overload assessment and management in heart failure patients.
AB  - Heart failure is a syndrome in which myocardial function is incapable of
      providing for normal physiologic needs. In the acute care setting, cardiac
      dysfunction primarily manifests with volume perturbations and presents with signs
      and symptoms of vascular congestion. Thus, in acute heart failure volume
      assessment is crucial in diagnosing and improving the prognosis. Also, goal
      directed therapy relies on accurate volume assessment to minimize the adverse
      outcomes of inappropriate, ineffective, or excessive diuresis. Currently, in most
      institutions clinical methods of volume assessment are the mainstay. However,
      these methods are highly dependent on the practitioners' skill level. In fact,
      there is a high variability between experienced physicians when assessing volume.
      As adjuncts, objective methods of volume assessment are being developed and used
      such as natriuretic peptides, bioimpedance analysis, and imaging.

PMID- 22365171
TI  - Diagnosis and management of fluid overload in heart failure and cardio-renal
      syndrome: the "5B" approach.
AB  - Cardio-Renal syndrome may occur as a result of either primarily renal or cardiac
      dysfunction. This complex interaction requires a tailored approach to manage the
      underlying pathophysiology while optimizing the patient's symptoms and thus
      providing the best outcomes. Patients often are admitted to the hospital for
      signs and symptoms of congestion and fluid overload is the most frequent cause of
      subsequent re-admission. Fluid management is of paramount importance in the
      strategy of treatment for heart failure patients. Adequate fluid status should be
      obtained but a target value should be set according to objective indicators and
      biomarkers. Once the fluid excess is identified, a careful prescription of fluid
      removal by diuretics or extracorporeal therapies must be made. While delivering
      these therapies, adequate monitoring should be performed to prevent unwanted
      effects such as worsening of renal function or other complications. There is a
      very narrow window of optimal hydration for heart failure patients. Overhydration
      can result in myocardial stretching and potential decompensation. Inappropriate
      dehydration or relative reduction of circulating blood volume may result in
      distant organ damage caused by inadequate perfusion. We suggest consideration of
      the "5B" approach. This stands for balance of fluids (reflected by body weight),
      blood pressure, biomarkers, bioimpedance vector analysis, and blood volume.
      Addressing these parameters ensures that the most important issues affecting
      symptoms and outcomes are addressed. Furthermore, the patient is receiving the
      best possible care while avoiding unwanted side effects of the treatment.

PMID- 22365170
TI  - Neutrophil gelatinase-associated lipocalin curve and neutrophil gelatinase
      associated lipocalin extended-range assay: a new biomarker approach in the early
      diagnosis of acute kidney injury and cardio-renal syndrome.
AB  - Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which
      multiple causative factors are involved. The time window between renal insult and
      development of acute kidney injury (AKI) in acute heart failure (AHF) can be
      varied in different patients and AKI often is diagnosed too late, only when the
      effects of the insult become evident with a loss or decline of renal function.
      For this reason, pharmaceutical interventions for AKI that have been shown to be
      renoprotective or beneficial when tested in experimental conditions do not
      display similar results in the clinical setting. In most cases patients with AHF
      are admitted with clinical signs and symptoms of congestion and fluid overload.
      Loop diuretics, typically used to induce an enhanced diuresis in these congested
      patients, often are associated with a subsequent significant decrease in
      glomerular filtration rate and cause a creatinine increase that is apparent
      within 72 hours. Early detection of AKI is not possible with the use of serum
      creatinine and there is a need for a timely diagnostic tool able to address renal
      damage while it is happening. We need to define the diagnosis of both AHF and AKI
      in the early phases of CRS type 1 by coupling a kidney damage marker such as
      neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide
      (BNP). Indeed, it would be ideal to make available a panel including whole blood
      or plasma cardiac and renal biomarkers building specific, pathophysiologically
      based, molecular profiles. Based on current knowledge and consensus, we can use
      kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI.
      However, differences in individual patient values and uncertainties about the
      ideal cut-off values may currently limit the application of these biomarkers. We
      propose that NGAL may increase its usefulness in the diagnosis and prevention of
      CRS if a curve of plasma values rather than a single plasma measurement is
      determined. To apply the concept of measuring an NGAL curve in AHF patients,
      however, assay performance in the lower-range values becomes a critical factor.
      For this reason, we propose the use of the new extended-range plasma NGAL assay
      that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF
      and lead to more effective intervention strategies.

PMID- 22365172
TI  - Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of
      olanzapine.
AB  - Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and
      is associated with substantial instability. The aim of this study was to
      investigate the instability of OLZ and to identify the degradants formed from its
      breakdown. Three experiments were conducted to monitor the degradation of OLZ and
      the formation of degradants in blood (1), water (2), and post-extraction at 4 
      degrees C (3). All three sample sets were analysed in duplicate and repeated in
      the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was
      identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl
      OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed
      the degradation of OLZ down in all three experiments and inhibited the formation
      of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on
      the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional
      experiment (4) was conducted. Sample sets were prepared containing different
      vortexing or sonication steps in order to alter the oxygen content in the
      samples. Statistical analysis confirmed that degradation increased significantly
      following vortexing for 1 min while sonication did not affect the rate of
      degradation of OLZ further suggesting the involvement of oxygen in the
      degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in
      aqueous solutions. It also degrades over time but its product is currently
      unknown and is under investigation.

PMID- 22365173
TI  - Treatment of estrogens and androgens in dairy wastewater by a constructed wetland
      system.
AB  - Constructed wetland systems (CWS) have been used as a low cost bio-filtration
      system to treat farm wastewater. While studies have shown that CWS are efficient
      in removing organic compounds and pathogens, there is limited data on the
      presence of hormones in this type of treatment system. The objective of this
      study was to evaluate the ability of the CWS to reduce estrogenic and androgenic
      hormone concentration in dairy wastewater. This was achieved through a year long
      study on dairy wastewater samples obtained from a surface flow CWS. Analysis of
      hormonal levels was performed using a solid phase extraction (SPE) sample clean
      up method, combined with reporter gene assays (RGAs) which incorporate relevant
      receptors capable of measuring total estrogenic or androgenic concentrations as
      low as 0.24 ng L(-1) and 6.9 ng L(-1) respectively. Monthly analysis showed a
      mean removal efficiency for estrogens of 95.2%, corresponding to an average
      residual concentration of 3.2 ng L(-1) 17beta-estradiol equivalent (EEQ), below
      the proposed lowest observable effect concentration (LOEC) of 10 ng L(-1).
      However, for one month a peak EEQ concentration of 115 ng L(-1) was only reduced
      to 18.8 ng L(-1). The mean androgenic activity peaked at 360 ng L(-1) and a
      removal efficiency of 92.1% left an average residual concentration of 32.3 ng L(
      1) testosterone equivalent (TEQ). The results obtained demonstrate that this type
      of CWS is an efficient system for the treatment of hormones in dairy wastewater.
      However, additional design improvements may be required to further enhance
      removal efficiency of peak hormone concentrations.

PMID- 22365174
TI  - Influence of secondary settling tank performance on suspended solids mass balance
      in activated sludge systems.
AB  - Secondary settling is the final step of the activated sludge-based biological
      waste water treatment. Secondary settling tanks (SSTs) are therefore an essential
      unit of producing a clear effluent. A further important function of SSTs is the
      sufficient thickening to achieve highly concentrated return sludge and biomass
      within the biological reactor. In addition, the storage of activated sludge is
      also needed in case of peak flow events (Ekama et al., 1997). Due to the
      importance of a high SST performance the problem has long been investigated
      (Larsen, 1977; Krebs, 1991; Takacs et al., 1991; Ekama et al., 1997; Freimann,
      1999; Patziger et al., 2005; Burger et al., 2011), however, a lot of questions
      are still to solve regarding e.g. the geometrical features (inflow, outflow) and
      operations (return sludge control, scraper mechanism, allowable maximum values of
      surface overflow rates). In our study we focused on SSTs under dynamic load
      considering both the overall unsteady behaviour and the features around the
      peaks, investigating the effect of various sludge return strategies as well as
      the inlet geometry on SST performance. The main research tool was a FLUENT-based
      novel mass transport model consisting of two modules, a 2D axisymmetric SST model
      and a mixed reactor model of the biological reactor (BR). The model was
      calibrated and verified against detailed measurements of flow and concentration
      patterns, sludge settling, accompanied with continuous on-line measurement of in-
      and outflow as well as returned flow rates of total suspended solids (TSS) and
      water. As to the inlet arrangement a reasonable modification of the geometry
      could result in the suppression of the large scale flow structures of the sludge
      water interface thus providing a significant improvement in the SST performance.
      Furthermore, a critical value of the overflow rate (q(crit)) was found at which a
      pronounced large scale circulation pattern develops in the vertical plane, the
      density current in such a way hitting the outer wall of the SST, turning then to
      the vertical direction accompanied with significant flow velocities. This
      phenomenon strengthens with the hydraulic load and can entrain part of the sludge
      thus resulting in unfavourable turbid effluent. As a representative case study an
      operating circular SST most commonly used in practice was investigated. Focusing
      on the sludge return strategies, it was found that up to a threshold peak flow
      rate the most efficient way is to keep the return sludge flow rate constant, at
      0.4Q(MAX). However, once the inflow rate exceeds the threshold value the return
      sludge flow rate should be slowly increased up to 0.6Q(MAX), performed in a
      delayed manner, about 20-30 min after the threshold value is exceeded. For
      preserving the methodology outlined in the present paper, other types of SSTs,
      however, need further individual investigations.

PMID- 22365175
TI  - Degradation of carbamazepine in environmentally relevant concentrations in water
      by Hydrodynamic-Acoustic-Cavitation (HAC).
AB  - The antiepileptic drug carbamazepine is one of the most abundant pharmaceuticals
      in the German aquatic environment. The effect of low carbamazepine concentrations
      (1-50 MUg L(-1)) is discussed controversially, but ecotoxicological studies
      revealed reproduction toxicity, decreased enzymatic activity and bioaccumulation
      in different test organisms. Therefore, as a preventive step, an efficient and
      cost-effective technique for wastewater treatment plants is needed to stop the
      entry of pharmaceuticals into the aquatic environment. Cavitation, the formation,
      growth, and subsequent collapse of gas- or vapor-filled bubbles in fluids, was
      applied to solve this problem. The technique of Hydrodynamic-Acoustic-Cavitation
      was used showing high synergistic effect. Under optimized conditions
      carbamazepine (5 MUg L(-1)) was transformed by pseudo-first order kinetics to an
      extent of >96% within 15 min (27% by hydrodynamic cavitation, 33% by acoustic
      cavitation). A synergistic effect of 63% based on the sum of the single methods
      was calculated. Carbamazepine concentrations were monitored by a sensitive and
      selective immunoassay and after 60 min no known metabolites were detectable by LC
      MS/MS.

PMID- 22365176
TI  - Optimal conduit choice in the absence of single-segment great saphenous vein for
      below-knee popliteal bypass.
AB  - BACKGROUND: Single-segment great saphenous vein (SSGSV) remains the conduit of
      choice for femoral to below-knee popliteal (F-BK) surgical revascularization. The
      purpose of this study was to determine the optimal conduit in patients with
      inadequate SSGSV. METHODS: This was a retrospective review of a prospectively
      maintained vascular registry. Patients underwent F-BK bypass with alternative
      vein (AV; arm vein, spliced GSV, or composite vein) or prosthetic conduit (PC).
      RESULTS: From January 1995 to June 2010, 83 patients had unusable SSGSV for F-BK
      popliteal reconstruction. Thirty-three patients had an AV conduit and 50 had PC.
      The AV group was a lower median age than the PC group (69 vs 75 years). The two
      groups were otherwise similar in comorbid conditions of diabetes mellitus (57.6%
      vs 58.0%; P > .99), smoking (15.2% vs 32.0%; P = .12), and hemodialysis (3% vs
      12%; P = .23). The groups were similar in baseline characteristics such as limb
      salvage as indication (93.9% vs 86.0%; P = .31), mean runoff score (5.2 vs 4.6; P
      = .39), and prior ipsilateral bypass attempts (18.2% vs 18.0%; P > .99). The AV
      and PC groups were also similar in 30-day mortality (6.1% vs 4.0%; P > .99) and
      wound infection rates (6.1% vs 6.0%; P > .99). PC patients were more likely to be
      discharged on Coumadin (Bristol-Myers Squibb, Princeton, NJ) than AV patients
      (62.0% vs 27.3%; P = .002). Seventeen of the 50 PC patients (34%) had a distal
      anastomotic vein cuff. A log-rank test comparison of 5-year outcomes for the AV
      and PC groups found no significant difference in primary patency (55.3% +/- 9.9%
      vs 51.9% +/- 10.8%; P = .82), assisted primary patency (68.8% +/- 9.6% vs 54.0%
      +/- 11.0%; P = .45), secondary patency (68.4% +/- 9.6% vs 63.7% +/- 10.4% for PC;
      P = .82), or limb salvage rates (96.2% +/- 3.8% vs 81.1% +/- 8.1%; P = .19).
      Multivariable analysis demonstrated no association between conduit type and loss
      of patency or limb. The factors most predictive of primary patency loss were limb
      salvage as the indication for surgery (hazard ratio [HR], 4.23; 95% confidence
      interval [CI], 1.65-10.9; P = .003) and current hemodialysis (HR, 3.51; 95% CI,
      1.08-11.4; P = .037). The most predictive factor of limb loss was current
      hemodialysis (HR, 7.02; 95% CI, 1.13-43.4; P = .036). CONCLUSIONS: For patients
      with inadequate SSGSV, PCs, with varying degrees of medical and surgical
      adjuncts, appear comparable to AV sources in graft patency for below-knee
      popliteal bypass targets. This observation is tempered by the small cohort sample
      size of this single-institutional analysis. Critical limb ischemia as the
      operative indication and current hemodialysis predict impaired patency, and
      hemodialysis is associated with limb loss.

PMID- 22365178
TI  - The influence of neck thrombus on clinical outcome and aneurysm morphology after
      endovascular aneurysm repair.
AB  - OBJECTIVE: This study investigated the influence of significant aneurysm neck
      thrombus in clinical and morphologic outcomes after endovascular aneurysm repair
      (EVAR). METHODS: The patient population was derived from a prospective EVAR
      database from two university institutions in The Netherlands from 2004 to 2008.
      Patients with significant thrombus in the neck (>2 mm in thickness in at least
      >25% of circumference) were identified as the thrombus group and were compared
      with the remaining patients without neck thrombus (no-thrombus group), treated
      within the same period. The primary end point was clinical success. Secondary end
      points included technical success and rates of decline in renal function.
      Detailed morphologic analysis of the aortic neck was serially performed for the
      thrombus group patients to assess changes in thrombus volume. RESULTS: The study
      included 389 patients: 43 (39 men; mean age of 72.3 years) met the criteria for
      the thrombus group; of these, 31 (72%) had significant thrombus in >50% of the
      aortic neck circumference, and 8 (19%) had circumferential thrombus >2-mm thick.
      Median follow-up was 3.34 years (interquartile range, 2.67-4.72). The estimated 5
      year clinical success rate was 74% for the thrombus group and 62% for the no
      thrombus group (P = .23). Endograft migration was more frequent in the thrombus
      group (P = .02). Multivariable Cox regression analysis showed a significant
      association between migration and use of a device without active fixation (hazard
      ratio, 4.9; 95% confidence interval, 1.31-18.23; P = .018) but not with the
      presence of neck thrombus (P = .063). No differences were found in the rates of
      decline in estimated glomerular filtration rate at 30 days and during follow-up
      between the thrombus and no-thrombus groups. The thrombus volume in the first 10
      mm of aortic neck was progressively reduced over time until it was not measurable
      in most patients, resulting in complete circular attachment of the endograft to
      the vessel wall. CONCLUSIONS: Our findings suggest that the presence of aneurysm
      neck thrombus has no significant influence on short-term and midterm EVAR
      results.

PMID- 22365177
TI  - Higher body mass index is associated with more adverse changes in calf muscle
      characteristics in peripheral arterial disease.
AB  - OBJECTIVE: This study investigated whether higher body mass index (BMI) is
      associated with more adverse lower extremity muscle characteristics at baseline
      and more adverse changes in muscle over time among participants with lower
      extremity peripheral arterial disease (PAD). METHODS: This was a longitudinal,
      observational study of 425 men and women with PAD and 261 without PAD. Computed
      tomography was used to measure calf muscle characteristics at baseline and every
      2 years. Knee extension isometric strength, power, and 6-minute walk distance
      were measured at baseline and annually. Baseline BMI (kg/m(2)) categories were
      ideal (20-25), overweight (>25-30), and obese (>30). Analyses adjust for age,
      race, sex, ankle brachial index, comorbidities, and other covariates. RESULTS: At
      baseline, higher BMI among participants with PAD was associated with greater calf
      muscle area (ideal BMI: 5181 mm(2); overweight: 5513 mm(2); obese: 5695 mm(2); P
      = .0009 for trend), higher calf muscle percentage of fat (6.38%, 10.28%, 17.44%,
      respectively, P < .0001 for trend), lower calf muscle density (P < .0001 for
      trend), and higher isometric knee extension strength (P = .015 for trend). Among
      participants with PAD, higher BMI was associated with greater declines in calf
      muscle area (P = .030 for trend) and greater increases in calf muscle percentage
      of fat (P = .023 for trend). Among participants without PAD, there were no
      significant associations of baseline BMI with changes in lower extremity muscle
      outcomes over time. CONCLUSIONS: Among PAD participants, higher BMI is associated
      with greater calf muscle area at baseline. However, higher BMI is associated with
      more adverse calf muscle density and calf muscle percentage of fat at baseline
      and greater declines in calf muscle area over time.

PMID- 22365179
TI  - Children balance theories and evidence in exploration, explanation, and learning.
AB  - We look at the effect of evidence and prior beliefs on exploration, explanation
      and learning. In Experiment 1, we tested children both with and without
      differential prior beliefs about balance relationships (Center Theorists, mean:
      82 months; Mass Theorists, mean: 89 months; No Theory children, mean: 62 months).
      Center and Mass Theory children who observed identical evidence explored the
      block differently depending on their beliefs. When the block was balanced at its
      geometric center (belief-violating to a Mass Theorist, but belief-consistent to a
      Center Theorist), Mass Theory children explored the block more, and Center Theory
      children showed the standard novelty preference; when the block was balanced at
      the center of mass, the pattern of results reversed. The No Theory children
      showed a novelty preference regardless of evidence. In Experiments 2 and 3, we
      follow-up on these findings, showing that both Mass and Center Theorists
      selectively and differentially appeal to auxiliary variables (e.g., a magnet) to
      explain evidence only when their beliefs are violated. We also show that children
      use the data to revise their predictions in the absence of the explanatory
      auxiliary variable but not in its presence. Taken together, these results suggest
      that children's learning is at once conservative and flexible; children integrate
      evidence, prior beliefs, and competing causal hypotheses in their exploration,
      explanation, and learning.

PMID- 22365180
TI  - Comparison of the principal proteins in bovine, caprine, buffalo, equine and
      camel milk.
AB  - Proteomic analysis of bovine, caprine, buffalo, equine and camel milk highlighted
      significant interspecies differences. Camel milk was found to be devoid of beta
      lactoglobulin, whereas beta-lactoglobulin was the major whey protein in bovine,
      buffalo, caprine, and equine milk. Five different isoforms of kappa-casein were
      found in camel milk, analogous to the micro-heterogeneity observed for bovine
      kappa-casein. Several spots observed in 2D-electrophoretograms of milk of all
      species could tentatively be identified as polypeptides arising from the
      enzymatic hydrolysis of caseins. The understanding gained from the proteomic
      comparison of these milks may be of relevance both in terms of identifying
      sources of hypoallergenic alternatives to bovine milk and detection of
      adulteration of milk samples and products.

PMID- 22365181
TI  - [Vertebral aspergillosis in a cirrhotic patient: an uncommon cause of
      spondylitis].

PMID- 22365182
TI  - [Venous thromboembolism in patients with HIV: A case series].

PMID- 22365183
TI  - Molecular epidemiology of fluoroquinolone resistance in invasive clinical
      isolates of Streptococcus pneumoniae in Seville.
AB  - INTRODUCTION: Due to the emergence of drug-resistant pneumococcal isolates, new
      fluoroquinolones have been recommended for the treatment of pneumococcal
      infections. The purpose of this study was to establish surveillance, and to
      conduct molecular characterization, of fluoroquinolone-resistant Streptococcus
      pneumoniae in Seville. METHOD: Norfloxacin-resistant S. pneumoniae isolates were
      characterized by quinolone resistance-determining region (QRDR) substitutions,
      reserpine-sensitive efflux, serotype and by pulsed-field gel electrophoresis
      (PFGE) patterns. RESULTS: Fourteen isolates (5.1%) showed an MIC>16 MUg/ml to
      norfloxacin. Eight of 10 adult isolates were susceptible to levofloxacin. The 4
      infant isolates with norfloxacin MIC>16 MUg/ml were susceptible to levofloxacin.
      Seven of these 12 low-level-resistant isolates had mutations in ParC, while
      mutations both in ParC and GyrA genes were only detected in one of the two high
      level-resistant isolates. All the isolates without QRDR substitutions that
      remained norfloxacin-resistant were positive for reserpine-inhibited efflux. The
      serotyping and PFGE revealed significant heterogeneity. We obtained 9 different
      profiles, 3 of which had two isolates each. Two of the isolates with the same
      pulsotype were from the same patient. The first isolate showed a mutation in the
      QRDR of ParC, and the second one had an additional GyrA mutation. CONCLUSION: In
      our study a levofloxacin resistance rate of 0.7% was found among invasive
      isolates. Although resistance level is low, surveillance is necessary, especially
      to prevent cases of in vivo resistance development as reported.

PMID- 22365184
TI  - "Underwater" EMR without submucosal injection for large sessile colorectal polyps
      (with video).
AB  - BACKGROUND: Submucosal injection is widely performed before EMR of large sessile
      colorectal polyps to facilitate resection and decrease perforation risk. We
      developed a novel method of water immersion ("underwater") EMR (UEMR) that
      eliminates submucosal injection. OBJECTIVE: To evaluate the feasibility and
      outcomes of UEMR without submucosal injection for large sessile colorectal
      polyps. DESIGN: Prospective, observational study. SETTING: Single, tertiary-care
      referral center. INTERVENTION: The standardized EMR technique involves full water
      immersion for the entire procedure and piecemeal resection with a 15-mm "duck
      bill" snare. MAIN OUTCOME MEASUREMENTS: Complete resection, bleeding,
      perforation, postpolypectomy syndrome, residual or recurrence adenoma. RESULTS:
      Sixty patients with 62 large sessile colorectal polyps underwent UEMR. The
      mean/median polyp size was 34/30 mm, and the mean/median resection time was 21/18
      minutes. Histology revealed the following: tubular adenoma (n = 22),
      tubulovillous adenoma (n = 19), villous adenoma (n = 4), serrated adenoma (n =
      11), and high-grade dysplasia/carcinoma in situ (n = 6). The mean/median interval
      until a follow-up colonoscopy in 54 patients (90%) was 20.4/15.2 weeks. One of 54
      patients (2%) had an adenoma smaller than 5 mm outside of the postresection scar,
      consistent with a residual lesion missed on index UEMR. COMPLICATIONS: There was
      no perforation or postpolypectomy syndrome. Delayed bleeding occurred in 3
      patients and was managed conservatively. LIMITATIONS: Limited follow-up; single
      center, single-endoscopist, uncontrolled study. CONCLUSIONS: The underwater
      resection technique enables complete removal of large sessile colorectal polyps
      without submucosal injection. The technique was safe in a large patient cohort,
      and the early recurrence rate appears low. Use of a water interface for UEMR has
      potential advantages that deserve further study.

PMID- 22365185
TI  - Parenteral nutrition in advanced cancer patients.
AB  - Parenteral nutrition (PN) is a medical treatment aimed at providing intravenous
      nutrients in patients in whom gastrointestinal function is partially or totally
      impaired. An obvious indication of PN in advanced cancer patients is the
      prevention and/or treatment of malnutrition in hypo-aphagic patients with
      intestinal failure due to the disease itself or the consequences of
      antineoplastic treatments. However, PN may also improve compliance with
      palliative radio/chemotherapy, reduce its side effects, enhance quality of life
      and prolong survival. A careful evaluation of patients' clinical conditions and
      families' expectations is mandatory before the decision to initiate PN in ACPs is
      taken, in order to avoid administration of an inappropriate or even life
      threatening medical treatment. Current available evidence indicates that patients
      expected to die earlier from the underlying tumour rather than from starvation
      gather no benefit from intravenous nutritional support. Although it is likely
      that intravenous nutrients provided to feed the patients are also utilized by
      cancer cells, at present there is no evidence that this translates into a
      clinically relevant harm to the patient. Fear of tumour growth stimulation must
      not be a reason for not considering parenteral nutrition in advanced cancer
      patients. The risk of septic, metabolic and mechanical complications has to be
      considered when PN support is prescribed, although a specialized and well trained
      medical and nursing staff may dramatically reduce complication rate. Decisions
      regarding treatment initiation and its possible withdrawal should be made based
      on the best available evidence and non on cultural and personal attitudes.

PMID- 22365186
TI  - Robotic sleeve gastrectomy after liver transplantation.

PMID- 22365187
TI  - Invited review: Mastitis in dairy heifers: nature of the disease, potential
      impact, prevention, and control.
AB  - Heifer mastitis is a disease that potentially threatens production and udder
      health in the first and subsequent lactations. In general, coagulase-negative
      staphylococci (CNS) are the predominant cause of intramammary infection and
      subclinical mastitis in heifers around parturition, whereas Staphylococcus aureus
      and environmental pathogens cause a minority of the cases. Clinical heifer
      mastitis is typically caused by the major pathogens. The variation in proportions
      of causative pathogens between studies, herds, and countries is considerable. The
      magnitude of the effect of heifer mastitis on an individual animal is influenced
      by the form of mastitis (clinical versus subclinical), the virulence of the
      causative pathogen(s) (major versus minor pathogens), the time of onset of
      infection relative to calving, cure or persistence of the infection when milk
      production has started, and the host's immunity. Intramammary infection in early
      lactation caused by CNS does not generally have a negative effect on subsequent
      productivity. At the herd level, the impact will depend on the prevalence and
      incidence of the disease, the nature of the problem (clinical, subclinical,
      nonfunctional quarters), the causative pathogens involved (major versus minor
      pathogens), the ability of the animals to cope with the disease, and the response
      of the dairy manager to control the disease through management changes. Specific
      recommendations to prevent and control mastitis in late gestation in
      periparturient heifers are not part of the current National Mastitis Council
      mastitis and prevention program. Control and prevention is currently based on
      avoidance of inter-sucking among young stock, fly control, optimal nutrition, and
      implementation of hygiene control and comfort measures, especially around
      calving. More risk factors for subclinical and clinical heifer mastitis have been
      identified (e.g., season, location of herd, stage of pregnancy) although they do
      not lend themselves to the development of specific intervention strategies
      designed to prevent the disease. Pathogen-specific risk factors and associated
      control measures need to be identified due to the pathogen-related variation in
      epidemiology and effect on future performance. Prepartum intramammary treatment
      with antibiotics has been proposed as a simple and effective way of controlling
      heifer mastitis but positive long-lasting effects on somatic cell count and milk
      yield do not always occur, ruling out universal recommendation of this practice.
      Moreover, use of antibiotics in this manner is off-label and results in an
      increased risk of antibiotic residues in milk. Prepartum treatment can be
      implemented only as a short-term measure to assist in the control of a
      significant heifer mastitis problem under supervision of the herd veterinarian.
      When CNS are the major cause of intramammary infection in heifers, productivity
      is not affected, making prepartum treatment redundant and even unwanted. In
      conclusion, heifer mastitis can affect the profitability of dairy farming because
      of a potential long-term negative effect on udder health and milk production and
      an associated culling risk, specifically when major pathogens are involved.
      Prevention and control is not easy but is possible through changes in young stock
      and heifer management. However, the pathogenesis and epidemiology of the disease
      remain largely unknown and more pathogen-specific risk factors should be
      identified to optimize current prevention programs.

PMID- 22365188
TI  - Invited review: Role of physically effective fiber and estimation of dietary
      fiber adequacy in high-producing dairy cattle.
AB  - Highly fermentable diets require the inclusion of adequate amounts of fiber to
      reduce the risk of subacute rumen acidosis (SARA). To assess the adequacy of
      dietary fiber in dairy cattle, the concept of physically effective neutral
      detergent fiber (peNDF) has received increasing attention because it amalgamates
      information on both chemical fiber content and particle size (PS) of the
      feedstuffs. The nutritional effects of dietary PS and peNDF are complex and
      involve feed intake behavior (absolute intake and sorting behavior), ruminal mat
      formation, rumination and salivation, and ruminal motility. Other effects include
      fermentation characteristics, digesta passage, and nutrient intake and
      absorption. Moreover, peNDF requirements depend on the fermentability of the
      starch source (i.e., starch type and endosperm structure). To date, the
      incomplete understanding of these complex interactions has prevented the
      establishment of peNDF as a routine method to determine dietary fiber adequacy so
      far. Therefore, this review is intended to analyze the quantitative effects of
      and interactions among forage PS, peNDF, and diet fermentability with regard to
      rumen metabolism and prevention of SARA, and aims to give an overview of the
      latest achievements in the estimation of dietary fiber adequacy in high-producing
      dairy cattle. Recently developed models that synthesize the effects of both peNDF
      and fermentable starch on rumen metabolism appear to provide an appropriate basis
      for estimation of dietary fiber adequacy in high-producing dairy cows. Data
      suggest that a period lasting more than 5 to 6h/d during which ruminal pH is <5.8
      should be avoided to minimize health disturbances due to SARA. The knowledge
      generated from these modeling approaches recommends that average amounts of 31.2%
      peNDF inclusive particles >1.18mm (i.e., peNDF(>1.18)) or 18.5% peNDF inclusive
      particles >8mm (i.e., peNDF(>8)) in the diet (DM basis) are required. However,
      inclusion of a concentration of peNDF(>8) in the diet beyond 14.9% of diet DM may
      lower DM intake level. As such, more research is warranted to develop efficient
      feeding strategies that encourage inclusion of energy-dense diets without the
      need to increase their content in peNDF above the threshold that leads to lower
      DM intake. The latter would require strategies that modulate the fermentability
      characteristics of the diet and promote absorption and metabolic capacity of
      ruminal epithelia of dairy cows.

PMID- 22365189
TI  - Comparison of heat stability of goat milk subjected to ultra-high temperature and
      in-container sterilization.
AB  - Goat milk with and without stabilizing salt was subjected to in-container and UHT
      sterilization. Heat stability was assessed by measuring the amount of sediment in
      the milk. Without stabilizing salts, goat milk usually produced less sediment
      when subjected to in-container sterilization compared with UHT processing.
      Addition of stabilizing salts up to 12.8mM resulted in a progressive increase in
      sediment for in-container sterilization. In contrast, adding stabilizing salts at
      6.4mM initially reduced sediment formation in UHT-treated milk but addition of
      stabilizing salts at 12.8mM increased sediment formation. Adding stabilizing
      salts to goat milk increased pH, decreased ionic calcium, and increased ethanol
      stability. Adding up to 2mM calcium chloride increased sediment formation more
      after UHT treatment than after in-container sterilization. These results suggest
      that no single mechanism or set of reactions causes milk to produce sediment
      during heating and that the favored pathway is different for UHT and in-container
      sterilization processes. Poor heat stability could be induced both by increasing
      ionic calcium and by decreasing it. Ethanol stability is not a good indicator of
      heat stability for in-container sterilization, but it may be for UHT
      sterilization, if milk does not enter the region of poor heat stability found at
      low concentrations of ionic calcium.

PMID- 22365190
TI  - A survey of the bacterial composition of kurut from Tibet using a culture
      independent approach.
AB  - Kurut (fermented yak milk) made by natural fermentation is a very important dairy
      food for the local people in Tibet (China). It is important to fully understand
      the bacterial composition of kurut for quality improvement and industrial
      production. Because more than 99% of prokaryotes cannot be cultured and
      identified by methods currently used in taxonomy, we applied a culture
      independent approach to explore the microbial biodiversity of this traditional
      food. In this study, a bacterial 16S rRNA gene clone library, including 460
      clones, was constructed using total DNA extracted from 30 samples of kurut. After
      screening by restriction fragment length polymorphism (RFLP) analysis, 56
      operational taxonomic units (OTU) with unique RFLP patterns were obtained. Then,
      1 representative sequence of every OTU was sequenced and phylogenetically
      analyzed. The representative phylotypes were affiliated with 5 groups, including
      Lactococcus lactis ssp. lactis, Lactobacillus helveticus, Streptococcus
      thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, and Acetobacter. In
      addition, nearly one-third of the representative clones (132 clones) had low
      similarity to species in GenBank (<97%), and these phylotypes were regarded as
      unknown bacteria. The characteristics of kurut are determined not only by lactic
      acid bacteria well known by the culture-dependent approach but also by bacteria
      that have not yet been identified.

PMID- 22365191
TI  - Identification of lactic acid bacteria in traditional fermented yak milk and
      evaluation of their application in fermented milk products.
AB  - In this study, 53 strains of lactic acid bacteria (LAB) isolated from Xueo, a
      traditional fermented yak milk in the western Sichuan Plateau of China, were
      identified and their use in fermented milk was evaluated. All gram-positive and
      catalase-negative strains were divided into 6 groups at the level of 87%
      similarity using amplified ribosomal DNA restriction analysis. These groups were
      identified as 6 species using 16S rDNA sequence analysis and atpA gene analysis.
      The dominant LAB strains in Xueo were Enterococcus durans, Lactobacillus
      fermentum, and Lactobacillus paracasei, accounting for 45.3, 22.6, and 17.0% of
      isolates, respectively. Milk fermented with most of the representative strains
      was high in quality, exhibiting relatively high viscosity, moderate acidity, good
      sensory quality, and high counts of viable LAB. Fermented milk of E. durans SCA16
      and L. fermentum SCA52 achieved the highest scores for overall sensory quality.
      Most strains displayed antimicrobial activity against at least 1 of 9 spoilage
      microorganisms. Lactic acid was the main factor inhibiting the growth of spoilage
      bacteria, and H(2)O(2) was also inhibitory to some extent. Excluding the
      influence of acid and H(2)O(2), strains SCA52 (L. fermentum) and SCA7
      (Lactobacillus plantarum) were antagonistic against some of the indicators,
      suggesting that the 2 strains may produce a bacteriocin-like substance.
      Therefore, the development of superior strains isolated from Xueo to ferment milk
      with similar flavor and texture to Xueo is expected.

PMID- 22365192
TI  - Identification of major milk fat globule membrane proteins from pony mare milk
      highlights the molecular diversity of lactadherin across species.
AB  - Although several studies have been devoted to the colloidal and soluble protein
      fractions of mare milk (caseins and whey proteins), to date little is known about
      the milk fat globule membrane (MFGM) protein fraction from mare milk. The
      objective of this study was thus to describe MFGM proteins from Equidae milk and
      to compare those proteins to already described MFGM proteins from cow and goat
      milk. Major MFGM proteins (namely, xanthine oxidase, butyrophilin, lactadherin,
      and adipophilin) already described in cow or goat milk were identified in mare
      milk using mass spectrometry. However, species-specific peculiarities were
      observed for 2 MFGM proteins: butyrophilin and lactadherin. A highly glycosylated
      70-kDa protein was characterized for equine butyrophilin, whereas proteins of 64
      and 67 kDa were characterized for cow and goat butyrophilin, respectively.
      Prominent differences across species were highlighted for lactadherin. Indeed,
      whereas 1 or 2 polypeptide chains were identified, respectively, by peptide mass
      fingerprinting matrix-assisted laser desorption/ionization-time of flight
      analysis for caprine and bovine lactadherin, 4 isoforms (60, 57, 48, and 45 kDa)
      for lactadherin from mare milk were identified by 10% sodium dodecyl sulfate
      PAGE. Polymerase chain reaction experiments on lactadherin transcripts isolated
      from milk fat globules revealed the existence of 2 distinct lactadherin
      transcripts in the horse mammary gland. Cloning and sequencing of both
      transcripts encoding lactadherin showed an alternative use of a cryptic splice
      site located at the end of intron 5 of the equine lactadherin-encoding gene. This
      event results in the occurrence of an additional alanine (A) residue in the
      protein that disrupts a putative atypical N-glycosylation site (VNGC/VNAGC)
      described in human lactadherin. Liquid chromatography coupled with tandem mass
      spectrometry analyses confirmed the existence of both lactadherin variants in
      mare MFGM. We show here that lactadherin from Equidae milk is much more complex
      than that from Bovidae milk (i.e., cow and goat milk), therefore raising
      questions regarding the precise function of these different isoforms, if any, in
      the equine mammary gland.

PMID- 22365193
TI  - The effects of information on willingness to pay for animal welfare in dairy
      production: application of nonhypothetical valuation mechanisms.
AB  - The objective of this study was to examine consumer willingness to pay (WTP) for
      animal welfare in dairy production using nonhypothetical Vickrey auctions and
      open-ended choice experiments. Two hundred fifteen subjects participated in
      experimental sessions with 4 types of dairy products (humane animal care-labeled
      cheese and ice cream and conventional cheese and ice cream) and 4 valuation
      mechanisms. Information treatment, which included information about humane animal
      care principles in dairy production, was used to examine the effects of
      information on WTP. The results showed that participants, on average, were
      willing to pay extra for a scoop of humane animal care-labeled ice cream above
      the price of conventional ice cream. However, no premium WTP for humane animal
      care-labeled cheese was detected. Furthermore, provision of information only
      about humane animal care principles in dairy production, without corresponding
      information about conventional production practices, did not increase WTP for
      humane animal care-labeled products.

PMID- 22365194
TI  - beta-Casein hydrolysate generated by the cell envelope-associated proteinase of
      Lactobacillus delbrueckii ssp. lactis CRL 581 protects against trinitrobenzene
      sulfonic acid-induced colitis in mice.
AB  - Lactobacillus delbrueckii ssp. lactis CRL 581, a thermophilic lactic acid
      bacterium used as a starter culture for the manufacture of several fermented
      dairy products, possesses an efficient proteolytic system that is able to release
      a series of potentially bioactive peptides (i.e., antihypertensive and
      phosphopeptides) from alpha- and beta-caseins. Considering the potential
      beneficial health effects of the peptides released by L. delbrueckii ssp. lactis
      CRL 581 from milk proteins, the aim of this work was to analyze the anti
      mutagenic and anti-inflammatory properties of the casein hydrolysates generated
      by the cell envelope-associated proteinase of this bacterium. The ability of
      alpha- and beta-casein hydrolysates to suppress the mutagenesis of a direct
      acting mutagen 4-nitroquinoline-N-oxide on Salmonella typhimurium TA 98 and TA
      100 increased concomitantly with the time of casein hydrolysis. The anti
      inflammatory effect of the beta-casein hydrolysate was evaluated using a
      trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease murine model. The
      hydrolysate was administered to mice 10 d before the intrarectal inoculation of
      TNBS. The mice that received beta-casein hydrolysate previously to TNBS showed
      decreased mortality rates, faster recovery of initial body weight loss, less
      microbial translocation to the liver, decreased beta-glucuronidase and
      myeloperoxidase activities in the gut, and decreased colonic macroscopic and
      microscopic damage compared with the animals that did not receive this
      hydrolysate. In addition, beta-casein hydrolysate exerted a beneficial effect on
      acute intestinal inflammation by increased interleukin 10 and decreased IFN-gamma
      production in the gut. Our findings are consistent with the health-promoting
      attributes of the milk products fermented by L. delbrueckii ssp. lactis CRL 581
      and open up new opportunities for developing novel functional foods.

PMID- 22365195
TI  - Effects of small-diameter silver nanoparticles on microbial load in cow milk.
AB  - Controlling bacterial growth in fluid milk is of economic interest, and
      supplemental methods to stop or reduce bacterial growth before and during the
      cooling chain may be valuable. Silver is effective in controlling growth of
      single-celled organisms, but has no effect on tissue cells. Smaller diameter (6-8
      nm) silver nanoparticles were produced, with purity over 99.99% (no chemical
      reaction used in the process), by using a terminated gas condensation principle.
      The first trial investigated effects of time, temperature, and accelerating
      voltages on total aerobic bacteria count in control milk and milk treated with
      silver nanoparticles. Metal braids were coated with silver nanoparticles using 3
      accelerating voltages, 0, 100, and 200V, the results of which indicated that the
      braids coated using 100V (AgNP100) were optimal. The AgNP100 particles were
      effective at all treatment temperatures and durations except for 10h, which
      indicated that the treated milk could be used after 10h for other dairy products
      such as yogurt, which require microbial activity. The second experiment
      investigated the effects of silver nanoparticles on counts of yeasts and molds,
      coliform bacteria, Escherichia coli, and Staphylococcus aureus in cow milk by
      treating milk with AgNP100 braids at 22  degrees C for 1h. Inductively coupled
      plasma mass spectrometry analyses indicated that the maximum amount of silver
      found in the AgNP100-treated milk was 6.1MUg/L, which is below the safety limits.
      Counts in milk samples containing the nanoparticle-coated braids were lower for
      all yeasts and molds and bacteria investigated compared with the control milk
      samples, which were kept under the same conditions but without the braids. The
      differences were significant for coliforms, Escherichia coli, and Staphylococcus
      aureus but not for yeasts and molds, although ranking of the counts (AgNP100 <
      initial load < control) were the same for all microorganisms. Small-diameter,
      silver nanoparticle-coated braids can stop or reduce bacterial growth in fluid
      milk. Silver nanoparticles inhibited microbial growth and may be useful in
      complementing the cooling chain and the thermal processes. These results warrant
      more research on the sensory properties and long-term safety of the use of silver
      nanoparticles in dairy products.

PMID- 22365196
TI  - Diacetyl levels and volatile profiles of commercial starter distillates and
      selected dairy foods.
AB  - Starter distillates (SDL) are used as ingredients in the formulation of many food
      products such as cottage cheese, margarine, vegetable oil spreads, processed
      cheese, and sour cream to increase the levels of naturally occurring buttery
      aroma associated with fermentation. This buttery aroma results, in part, from the
      presence of the vicinal dicarbonyl, diacetyl, which imparts a high level of
      buttery flavor notes and is a key component of SDL. Diacetyl (2,3-butanedione) is
      a volatile product of citrate metabolism produced by certain bacteria, including
      Lactococcus lactis ssp. diacetylactis and Leuconostoc citrovorum. In the United
      States, SDL are regarded as generally recognized as safe ingredients, whereby
      usage in food products is limited by good manufacturing practices. Recently,
      diacetyl has been implicated as a causative agent in certain lung ailments in
      plant workers; however, little is published about the volatile composition of SDL
      and the levels of diacetyl or other flavoring components in finished dairy
      products. The objective of this work was to characterize the volatile compounds
      of commercial SDL and to quantitate levels of diacetyl and other Flavor and
      Extract Manufacturers Association-designated high-priority flavoring components
      found in 18 SDL samples and 24 selected dairy products. Headspace volatiles were
      assessed using a solid-phase microextraction and analyzed by gas chromatography
      mass spectrometry. In addition to diacetyl (ranging from 1.2 to 22,000 MUg/g), 40
      compounds including 8 organic acids, 4 alcohols, 3 aldehydes, 7 esters, 3 furans,
      10 ketones, 2 lactones, 2 sulfur-containing compounds, and 1 terpene were
      detected in the SDL. A total of 22 food samples were found to contain diacetyl
      ranging from 4.5 to 2,700 MUg/100g. Other volatile compounds, including
      acetaldehyde, acetic acid, acetoin, benzaldehyde, butyric acid, formic acid,
      furfural, 2,3-heptanedione, 2,3-pentanedione, and propanoic acid, were also
      identified and quantified in SDL or food samples, or both. The results obtained
      in this work summarize the volatile composition of commercial SDL and the
      approximate levels of diacetyl and other Flavor and Extract Manufacturers
      Association-designated high-priority flavoring components found in SDL and
      selected dairy foods.

PMID- 22365197
TI  - The effect of substitution of sodium chloride with potassium chloride on the
      physicochemical, microbiological, and sensory properties of Halloumi cheese.
AB  - This study investigated the effect of salt reduction and partial replacement with
      KCl on the microbiological and sensory characteristics of fresh and matured
      Halloumi cheese. Halloumi samples were matured for 8 wk and moisture, fat,
      protein, pH, lactic acid, sodium, and potassium contents determined. Instrumental
      textural characteristics of the samples were measured using a texture analyzer.
      Microbiological analyses included counts of total bacteria, lactic acid bacteria,
      yeasts and molds, total coliforms, and psychrophilic bacteria. Descriptive
      sensory analysis was carried out by a 9-member panel, and acceptability testing
      was conducted with 72 panelists. Salt treatment had a significant effect on the
      pH, sodium, and potassium contents of the cheeses, whereas age by salt treatment
      interaction had a significant effect on the pH, lactic acid, and potassium
      contents of the samples. No major trends could be discerned from the texture
      profile analysis. All tested microorganisms increased with storage but in general
      did not differ between treatments and were, in certain instances, lower than
      levels reported in the literature for other cheeses. Descriptive analysis
      revealed a significant difference between salt treatments for bitterness,
      crumbliness, and moistness, whereas age of cheese was significant for saltiness
      and squeakiness. Salt treatment had no significant effect on any of the
      acceptability variables for all Halloumi samples.

PMID- 22365198
TI  - Determination of sialic acids in infant formula by chromatographic methods: a
      comparison of high-performance anion-exchange chromatography with pulsed
      amperometric detection and ultra-high-performance liquid chromatography methods.
AB  - Sialic acid determination in an infant formula presents many challenges,
      including efficient sialic acid release from glycoconjugates, effective sample
      preparation, and rugged chromatography. This work compares 2 chromatographic
      assays developed for determination of sialic acids in infant formula. Prior to
      chromatography, both assays release sialic acids by acid hydrolysis and treat the
      hydrolysate with a subsequent anion-exchange sample preparation. Both high
      performance anion-exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD) and fluorescence ultra-high-performance liquid chromatography (UHPLC)
      sample analysis methods were evaluated to compare assay performance and
      convenience. Calibration ranges were chosen to encompass the expected amounts of
      2 sialic acids in infant formula: N-acetylneuraminic acid (Neu5Ac) and N
      glycolylneuraminic acid (Neu5Gc). Response was linear by either method with
      coefficients of determination of 1.00 by HPAEC-PAD between 5.0 and 100pmol of
      Neu5Ac and between 0.34 and 6.8 pmol of Neu5Gc and >0.99 by UHPLC between 5.0 and
      260 pmol of Neu5Ac and between 0.20 and 9.8 pmol of Neu5Gc. Both methods had
      sufficient sensitivity to determine these sialic acids in infant formula. Three
      infant formulas were analyzed to evaluate accuracy and precision of the assays.
      The HPAEC-PAD assay was found to be faster overall and the UHPLC assay was more
      sensitive. Reaction efficiency, and therefore sensitivity, was dependent on the
      sample matrix. This work illustrates sample-specific complexity that must be
      considered in choosing an assay.

PMID- 22365199
TI  - Short communication: Examination of milk filters by real-time PCR as a herd-level
      indicator of the presence of Mycobacterium avium subspecies paratuberculosis in
      dairy herds.
AB  - The aim of this study was to assess the suitability of real-time quantitative PCR
      (qPCR) for the detection of Mycobacterium avium ssp. paratuberculosis (MAP) in
      milk filters as a herd level indicator of paratuberculosis infection. Seventy
      nine samples from textile or metal milk filters from 15 herds with defined MAP
      prevalence (infection status = noninfected, 0-5%, 5-10%, or >10% of animals with
      clinically confirmed paratuberculosis) were analyzed. The MAP DNA was isolated by
      a modified commercially available protocol for feces, and detection and
      quantification of the pathogen was performed by the IS900 qPCR. Mycobacterium
      avium ssp. paratuberculosis DNA was detected in 63 (79.7%) samples. Determination
      of MAP infection established by fecal and tissue culture was correctly confirmed
      by the analysis of milk filters on 11 of 12 infected farms; MAP was not detected
      in filters from 3 farms where paratuberculosis was never diagnosed. Statistical
      analysis of the data supports the evidence that milk filters can be used as a
      template for the direct detection of MAP on the herd level. The probability of
      successful MAP detection in milk filters in a herd with MAP-infected cows is at
      least 94.3%. Absolute numbers of MAP detected on the milk filter can be used for
      a rough estimation of paratuberculosis prevalence >10% in the herd. Analysis of
      milk filters for the presence of MAP can be a useful tool for the detection of
      paratuberculosis on the herd level before any individual control strategies.

PMID- 22365200
TI  - Short communication: Detection of Shiga toxin-producing Escherichia coli (STEC)
      in healthy cattle and pigs in Lima, Peru.
AB  - The aim of this study was to determine the prevalence of Shiga toxin-producing
      Escherichia coli (STEC) in cattle and pigs as a possible STEC reservoir in Lima,
      Peru. One hundred and fourteen cattle and 112 pigs from 10 and 4 farms,
      respectively, were studied. Five E. coli colonies per culture were studied by a
      multiplex real-time PCR to identify Shiga toxin-producing (stx1, stx2, eaeA),
      enterotoxigenic (lt, st), enteropathogenic (eaeA), enteroinvasive (ipaH),
      enteroaggregative (aggR), and diffusely adherent E. coli (daaD). Shiga toxin
      producing E. coli were isolated from 16 cattle (14%) but none from pigs. stx1 was
      found in all bovine isolates, 11 of which also carried eaeA genes (69%); only 1
      sample had both stx1 and stx2. Thirteen stx-positive strains were classified as
      Shiga-toxigenic (81%) using an enzymatic immunoassay, 2 STEC strains were from
      serogroup O157 (13%), and 7 were sorbitol negative (44%). Enteropathogenic E.
      coli were detected more frequently in cattle (18%, 20/114) than in pigs (5%,
      6/112). To our knowledge, this is the first study on the prevalence of STEC in
      farms animals in Peru using molecular methods. Further studies are needed in a
      large number of farms to determine the relevance of these findings and its
      consequences for public health.

PMID- 22365201
TI  - The effect of premilking udder preparation on Holstein cows milked 3 times daily.
AB  - Premilking udder preparation (including forestripping and duration of lag time
      the time between first tactile stimulation and attachment of milking unit) might
      influence milking measures such as milking unit on-time, incidence of bimodality,
      and milk flow rates in Holstein cows milked 3 times daily. Holstein cows (n=786)
      from an 1,800-cow commercial dairy herd were enrolled under a restricted
      randomized design to determine the effect of 9 different premilking routines. Lag
      times were 0, 60, 90, 120, and 240s and included forestripping or no
      forestripping for a total of 9 treatments (no forestripping for 0 lag time); the
      study was conducted from February to November 2008. All cow-treatment
      combinations were compared with the control: predipping plus forestripping and
      drying with 90s of lag time. Cows were initially assigned to 1 of 3 treatments
      for a period of 7d and upon completion of the first 7-d period were reassigned to
      a different treatment until all treatments had been completed. From one treatment
      period to the next, cows had to switch stimulation method with no restriction on
      lag time. Cows did not receive all treatments during the duration of the trial.
      Early- to mid-lactation cows (EML; 17-167 DIM) and late-lactation cows (LL; 174
      428 DIM) were housed in 2 different pens. Milk yield was significantly different
      between dip + forestrip and dip+dry for 2 of the treatments for EML cows compared
      with dip + forestrip and 90 s of lag-time (DF90); however, this was not thought
      to be due to treatment because the significant lag times were very different (60
      and 240 s) and neither was an extreme value. Milk yield did not differ with
      treatment for the LL cows. Milking unit on-time did not differ when comparing all
      treatments for EML with treatment DF90; however, an increase in milking unit on
      time occurred when lag time was 60s or less for LL cows. The highest incidence of
      bimodal milk curves was when lag time = 0 and this was independent of stage of
      lactation; a lag time of 240 s had the second-highest incidence of bimodal milk
      curves for EML and LL cows. Milk harvested in the first 2 min was lower for lag
      times of 0 and 240 s when compared with DF90. Increasing the lag time for all
      cows appeared to improve overall milking time efficiency (although lag time had
      no effect on EML cows).

PMID- 22365202
TI  - A reduction in milking frequency and feed allowance improves dairy cow immune
      status.
AB  - Twice-daily milking is the most common milking regimen used globally. A reduction
      in milking frequency to once daily, combined with a reduced feed allowance (FA),
      could reduce the physiological stress associated with the transition to peak milk
      production, and hence improve immune function. This study investigated how
      milking frequency and FA affect dairy cow immune status. Cows (n = 48) were
      milked once a day (OAD) or twice a day (TAD) on 1 of 2 FA: high (HFA) or low
      (LFA), in a 2 * 2 factorial arrangement of treatments. After the mean calving
      date of March 11, HFA cows were offered ad libitum grass silage and 7 kg of
      concentrates/cow per day until March 22, then 4 kg of concentrates/cow per day
      until April 17, and thereafter allocated 31.3 kg of dry matter (DM) grass/cow per
      day. The LFA cows were offered 4 kg of concentrates/cow per day, 1 kg of
      concentrates/cow per day, and allocated 19 kg of DM grass/cow per day for the
      same respective periods. Milk yield was recorded daily and body condition score
      weekly, and somatic cell count was performed at approximately 2-wk intervals.
      Blood samples were collected prepartum (d -7 to -1) and at d 1 to 7, d 14 to 21,
      and d 42 to 49 postpartum. Total and differential leukocyte percentage, IFN-gamma
      production in response to concanavalin A and phytohemagglutinin, and cortisol,
      haptoglobin (Hp), and serum amyloid A (SAA) concentrations were evaluated. Cows
      milked OAD had reduced milk yield and body reserve mobilization, but higher
      somatic cell counts. Milking frequency and diet had no effect on total leukocyte
      counts. Cows milked OAD had a higher lymphocyte percentage and lower monocyte
      percentage, and tended to have a lower neutrophil percentage than cows milked
      TAD. In addition, the LFA cows had a higher eosinophil percentage than cows fed
      the HFA. Milking frequency and diet had no effect on IFN-gamma, Hp, SAA, or
      cortisol production. Utilization of strategies to reduce milk yield at the
      beginning of the lactation could not only reduce body reserve mobilization, but
      also help to maintain a functioning immune system, and thus improve cow welfare.

PMID- 22365203
TI  - Characterization of bovine glucose transporter 1 kinetics and substrate
      specificities in Xenopus oocytes.
AB  - Glucose is an essential substrate for lactose synthesis and an important energy
      source in milk production. Glucose uptake in the mammary gland, therefore, plays
      a critical role in milk synthesis. Facilitative glucose transporters (GLUT)
      mediate glucose uptake in the mammary gland. Glucose transporter 1 (GLUT1) is the
      major facilitative glucose transporter expressed in the bovine mammary gland and
      has been shown to localize to the basolateral membrane of mammary epithelial
      cells. Glucose transporter 1 is, therefore, thought to play a major role in
      glucose uptake during lactation. The objective of this study was to determine the
      transport kinetic properties and substrate specificity of bovine GLUT1 using the
      Xenopus oocyte model. Bovine GLUT1 (bGLUT1) was expressed in Xenopus oocytes by
      microinjection of in vitro transcribed cRNA and was found to be localized to the
      plasma membrane, which resulted in increased glucose uptake. This bGLUT1-mediated
      glucose uptake was dramatically inhibited by specific facilitative glucose
      transport inhibitors, cytochalasin B, and phloretin. Kinetic analysis of bovine
      and human GLUT1 was conducted under zero-trans conditions using radio-labeled 2
      deoxy-D-glucose and the principles of Michaelis-Menten kinetics. Bovine GLUT1
      exhibited a Michaelis constant (K(m)) of 9.8 +/- 3.0mM for 2-deoxy-d-glucose,
      similar to 11.7 +/- 3.7 mM for human GLUT1. Transport by bGLUT1 was inhibited by
      mannose and galactose, but not fructose, indicating that bGLUT1 may also be able
      to transport mannose and galactose. Our data provides functional insight into the
      transport properties of bGLUT1 in taking up glucose across mammary epithelial
      cells for milk synthesis.

PMID- 22365204
TI  - Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of
      dairy cows.
AB  - Endocrines and metabolites in the circulation act as long-term hunger or satiety
      signals in the brain during negative energy balance and play an important role in
      the control of feed intake. These signals also occur in the cerebrospinal fluid
      (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed
      intake regulation. Thus CSF functions as a transport medium for fuel signals
      between blood and brain. The CSF metabolite concentrations are mainly under
      control of the blood-brain barriers, which provide specific carrier molecules
      facilitating the entry of substances required by the brain and protect the brain
      from factors that could impair neuronal function. The transport of small
      molecules such as amino acids (AA) across the blood-brain barriers may be limited
      by competing AA that share a common transporter for the uptake into brain.
      Consequently, CSF metabolite concentrations differ from those in blood. Thus it
      appears likely that central (CSF) rather than peripheral (blood) metabolites act
      as pivotal signals for the control of feed intake. However, the contribution of
      putative orexigenic and anorexigenic signals in CSF of cows has not been studied
      so far. Therefore, the aim of this study was to elucidate associations existing
      between both plasma and CSF metabolites, each in response to feed restriction
      induced negative energy balance. Seven German Holstein dairy cows, between 87 and
      96 DIM of the second lactation (milk yield, 27.9 L/d) were fed ad libitum (AL)
      for 4 d and CSF from the spinal cord and blood from the jugular vein was
      withdrawn before morning feeding at the fifth day. Subsequently, animals were
      feed restricted (R) to 50% of the previous AL intake for 4 d and CSF and plasma
      were collected at the ninth day. Body weight, feed intake, water intake, and milk
      production were determined. Thirty-one AA, beta-hydroxybutyric acid, cholesterol,
      glucose, lactate, nonesterified fatty acids, urea, and osmolality were measured
      in both CSF and plasma, whereas free fatty acids and volatile fatty acids were
      determined in plasma only. Although plasma arginine (132%), leucine (134%),
      lysine (117%), nonesterified fatty acids (224%), and cholesterol (112%)
      increased, tryptophan and carnosine decreased (-33% and -20%, respectively) in R
      animals as compared with AL animals. In CSF, concentrations of these metabolites
      were not affected after R feeding, suggesting that these identified plasma
      metabolites have only little potential to contribute to central feed intake
      regulatory signaling in cows. By contrast, in CSF, serine, threonine, and
      tyrosine decreased (-20, -24, and -31%, respectively) after R feeding. Therefore,
      these 3 AA are potential centrally acting anorexigenic signals in cows.

PMID- 22365205
TI  - Antimicrobial use on Canadian dairy farms.
AB  - Antimicrobial use (AMU) data are critical for formulating policies for containing
      antimicrobial resistance. The present study determined AMU on Canadian dairy
      farms and characterized variation in AMU based on herd-level factors such as milk
      production, somatic cell count, herd size, geographic region and housing type.
      Drug use data were collected on 89 dairy herds in 4 regions of Canada, Alberta,
      Ontario, Quebec, and the Maritime provinces (Prince Edward Island, New Brunswick,
      and Nova Scotia) for an average of 540 d per herd. Dairy producers and farm
      personnel were asked to deposit empty drug containers into specially provided
      receptacles. Antimicrobial use was measured as antimicrobial drug use rate
      (ADUR), with the unit being number of animal defined-daily doses (ADD)/1,000 cow
      days. Antimicrobial drug use rates were determined at farm, region, and national
      level. Combined ADUR of all antimicrobial classes was 14.35 ADD/1,000 cow-days
      nationally. National level ADUR of the 6 most commonly used antimicrobial drug
      classes, cephalosporins, penicillins, penicillin combinations, tetracyclines,
      trimethoprim-sulfonamide combinations, and lincosamides were 3.05, 2.56, 2.20,
      1.83, 0.87, and 0.84 ADD/1,000 cow-days, respectively. Dairy herds in Ontario
      were higher users of third-generation cephalosporins (ceftiofur) than in Quebec.
      Alberta dairy herds were higher users of tetracyclines in comparison to
      Maritimes. Antimicrobial drug use rate was higher via systemic route as compared
      with intramammary and other routes of administration (topical, oral, and
      intrauterine). The ADUR of antimicrobials used intramammarily was higher for
      clinical mastitis treatment than dry cow therapy. For dry cow therapy, penicillin
      ADUR was greater than ADUR of first-generation cephalosporins. For clinical
      mastitis treatment, ADUR of intramammary penicillin combinations was greater than
      ADUR of cephapirin. Herd-level milk production was positively associated with
      overall ADUR, ADUR of systemically administered ceftiofur, cephapirin
      administered for dry cow therapy, and pirlimycin administered for clinical
      mastitis treatment. Herd size and ADUR of systemically administered ceftiofur
      were also positively associated. In conclusion, beta-lactams were most commonly
      used on Canadian dairy farms. Among antimicrobials of very high importance in
      human medicine, the use of fluoroquinolones was rare, whereas third-generation
      cephalosporins and penicillin combinations containing colistin were used very
      frequently on Canadian dairy farms.

PMID- 22365206
TI  - Effect of conjugated linoleic acid supplementation on body composition, body fat
      mobilization, protein accretion, and energy utilization in early lactation dairy
      cows.
AB  - The objective of the study was to investigate the effects of trans-10,cis-12 and
      cis-9,trans-11 conjugated linoleic acid (CLA) supplementation on body
      composition, mobilization or accretion of body fat and protein mass, as well as
      the energy metabolism of dairy cows during the first 105 d in milk (DIM). For
      this purpose, a comparative slaughter experiment was conducted with 25
      primiparous German Holstein cows. The experiment started at 1 DIM with the
      slaughter of 5 animals of an initial group receiving no CLA supplement. The
      remaining animals were fed a CLA supplement (n=10) or a stearic acid-based
      control fat supplement (CON; n=10) from 1 DIM up to slaughter. After 42 DIM, 5
      more cows from each treatment (42-CLA and 42-CON) were slaughtered. The remaining
      5 cows in each treatment were slaughtered after 105 DIM (105-CLA and 105-CON).
      The animals of the CLA groups consumed 6.0 g/d of trans-10,cis-12 CLA and 5.7 g/d
      of cis-9,trans-11 CLA. During the slaughter process, the empty body mass was
      recorded and partitioned into 9 fractions (meat, bone, offal, hide, mammary
      gland, retroperitoneal fat, omental fat, mesenteric fat, and s.c. fat). The
      fractions were analyzed for dry matter, ether extract, crude protein, and ash to
      calculate the body composition of the empty body mass at the different slaughter
      times. The principle of the comparative slaughter technique was applied to
      estimate body fat or protein mobilization and accretion in the viewed periods
      from 1 DIM until 42 and 105 DIM. The heat production (HP) was calculated by
      subtracting the energy in milk and energy changes in body mass from the
      metabolizable energy intake. The body composition was not affected by CLA
      supplementation. However, the mobilization of body fat mass from 1 until 42 DIM
      was 24.1 kg in the 42-CON group and 14.3 kg in the 42-CLA group. This resulted in
      a trend to lower body mass (fat and protein) mobilization of 10.5 kg in the 42
      CLA group. Energy mobilization from body mass was 21.2 MJ/d in the 42-CON and
      11.5 MJ/d in the 42-CLA group. The HP was unchanged for the 42-CON and 42-CLA
      group with 123.0 and 116.9 MJ/d, respectively. From 1 until 105 DIM, the protein
      accretion was 4.3 kg and the daily energy retention in body protein was 1.0 MJ
      higher for CLA-supplemented cows. The HP was decreased in this period for the 105
      CLA group (115.5 MJ/d) as compared with the 105-CON group (125.9 MJ/d). Overall,
      the trend for a decreased body mass mobilization suggested a protective effect of
      CLA supplementation against excessive use of body reserves within 42 DIM.
      Continuous CLA supplementation until 105 DIM increased protein accretion. The
      effects on body mass mobilization and protein accretion in combination with the
      decreased HP in the CLA-fed cows suggested a more efficient utilization of
      metabolizable energy in CLA-supplemented early lactation dairy cows.

PMID- 22365207
TI  - Associations of subclinical hypocalcemia at calving with milk yield, and feeding,
      drinking, and standing behaviors around parturition in Holstein cows.
AB  - The objectives of this study were to describe the associations of subclinical
      hypocalcemia with milk yield, and feeding, drinking, and resting behavior during
      the period around calving. Blood was sampled within 24h of calving and analyzed
      for serum total calcium. Fifteen Holstein dairy cows were classified as having
      subclinical hypocalcemia (serum calcium concentration <= 1.8 mmol/L, without
      clinical milk fever) and were matched with 15 control cows (serum calcium
      concentration >1.8 mmol/L) based on parity and presence of other diseases. Daily
      feeding and drinking behavior were monitored using an electronic feeding system
      (Insentec, BV, Marknesse, the Netherlands) and summarized by week relative to
      calving (wk -3, -2, -1, +1, +2, and +3). Standing behavior was monitored from 7 d
      before until 7 d after calving using dataloggers. Daily milk yields were obtained
      for all cows up to 280 d in milk (DIM). These data were summarized by week for
      the first 4 wk of lactation to assess short-term differences in milk yield, and
      were summarized into 4-wk periods to assess long-term (280 DIM) differences in
      milk yield between groups. Cows with subclinical hypocalcemia produced, on
      average, 5.7 kg/d more milk during wk 2, 3, and 4 compared with control cows;
      however, only subclinically hypocalcemic cows in their third lactation sustained
      greater milk yields throughout 280 DIM. Despite greater milk yield during the
      weeks following calving, cows with subclinical hypocalcemia did not consume more
      water after calving and tended to have greater dry matter intake only during wk
      2. However, these animals made fewer visits to the water bins during the first 2
      wk after calving and tended to make fewer visits to the feed bins during wk 1 and
      3, suggesting that they used these resources more efficiently. Dry matter intake
      was, on average, 1.7 kg/d greater during wk -2 and -1 among cows subsequently
      diagnosed with subclinical hypocalcemia compared with control cows but neither
      group was lactating during this period. Cows with subclinical hypocalcemia stood
      for 2.6h longer during the 24-h period before parturition, which may suggest
      these animals experience increased discomfort at calving; these cows spent 2.7h
      less time standing during d +1. Although milk yield was greater among cows with
      subclinical hypocalcemia, this study controlled for the confounding effects of
      disease incidence; these results do not refute previous research that associates
      subclinical hypocalcemia with an increased risk for health disorders. The
      mechanisms by which subclinical hypocalcemia is associated with behavior and
      production require further investigation.

PMID- 22365208
TI  - Gluconeogenic enzymes are differentially regulated by fatty acid cocktails in
      Madin-Darby bovine kidney cells.
AB  - Expression of mRNA for pyruvate carboxylase (PC) is elevated at calving and
      during other physiological states when plasma NEFA concentrations are increased.
      The objective of this study was to determine the direct effects of fatty acids on
      expression of PC, cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C),
      mitochondrial PEPCK (PEPCK-M), and glucose-6-phosphatase (G6Pase) mRNA in Madin
      Darby bovine kidney (MDBK) cells. Combinations of C14:0, C16:0, C18:0, C18:1n-6
      cis, C18:2n-6 cis, and C18:3n-3 cis were created to mimic the profiles and
      concentrations in serum from far-off dry cows and late postcalving intervals
      (PRPT), the profile at calving (CALV), and the profile observed in cows induced
      to express fatty liver at calving (IFL). The MDBK cells were exposed to fatty
      acid mixtures for 24h at the following concentrations: 0.25 and 0.5mM for PRPT;
      0.25, 0.5, and 1.0mM for CALV; and 0.5 and 1.0mM for IFL. Cells exposed to PRPT
      had greater PEPCK-C and tended to have greater G6Pase mRNA than control cells.
      Exposure of cells to 0.25mM PRPT increased expression of PEPCK-C compared with
      cells exposed to 0.5mM PRPT. Expression of PC and PEPCK-M did not differ with
      exposure to PRPT. Expression of PEPCK-C was decreased and that of PEPCK-M and
      G6Pase mRNA increased linearly in response to CALV. The ratio of PC:PEPCK-C mRNA
      was increased by the IFL mixture and in response to increasing amounts of the
      CALV fatty acid mixture. Treatment of cells with CALV or IFL increased the sum of
      PC 5' untranslated region (UTR) variants A, B, C, and F but did not alter PC 5'
      UTR D and E expression. The changes in PEPCK-C, G6Pase, and PC mRNA and the ratio
      of PC:PEPCK-C observed in MDBK cells in response to fatty acids suggests a role
      for fatty acid concentration and profile in mediating the expression of key
      gluconeogenic enzymes.

PMID- 22365209
TI  - The association between metabolic parameters and oocyte quality early and late
      postpartum in Holstein dairy cows.
AB  - The objective of this was to study the association between metabolic parameters
      and oocyte quality in postpartum lactating dairy cows as assessed by oocyte
      morphology and development after fertilization and culture in vitro. Holstein
      Friesian spring-calving cows were used (n = 16, parity 3.0 +/- 0.36, weight at
      calving 611 +/- 16.2 kg, previous 305-d milk yield 6,454.0 +/- 276.4 kg).
      Bodyweight (BW) and body condition score were recorded at approximately 2 wk
      before expected calving date, at calving, and then weekly until the end of the
      experiment (approximately 80 d postpartum). Blood plasma samples were collected
      weekly, starting 2 wk before the expected calving date and continuing until the
      end of the experiment and were analyzed for nonesterified fatty acids (NEFA),
      beta-hydroxybutyrate (BHBA), insulin, insulin-like growth factor-I, and glucose.
      Transvaginal oocyte recovery was carried out twice weekly on each cow for a
      period of approximately 12 wk starting 14 d after calving until approximately 80
      d postpartum. A linear decrease in BW was observed from calving (d 0) to d 28,
      after which it remained stable. Body condition score decreased from 14 d
      precalving, reaching a nadir at approximately d 35 to 42, after which it
      increased to the end of the period. Nonesterified fatty acid concentrations were
      significantly elevated from the week before calving until d 42 postcalving,
      whereas BHBA concentration was significantly elevated from calving to d 49
      postcalving. Insulin-like growth factor-I concentration dramatically decreased
      from d -14 to a nadir on d 7. A significant increase in glucose concentration
      occurred from d -7 to d 0, followed by a precipitous decrease to d 7. Based on
      the metabolic profiles (particularly NEFA and BHBA concentrations), data from d 0
      to 42 postpartum (period 1) were compared with corresponding data from d 42 to 80
      (period 2). Apart from body condition score, all of the physiological parameters
      measured (milk yield, BW, and blood metabolites) differed significantly between
      the 2 periods. In particular, insulin-like growth factor-I, insulin, and glucose
      concentrations were higher post-d 42, whereas BHBA and NEFA were lower compared
      with pre-d 42 postpartum. The number of oocytes recovered per session and oocyte
      quality grade did not differ between periods. Positive associations of follicles
      aspirated and insulin, BHBA, and NEFA were detected. The number of oocytes
      recovered was positively associated with milk yield, BW, and glucose and NEFA
      concentrations. The number of cleaved oocytes was positively associated with BW
      and NEFA concentration. In conclusion, the data do not provide evidence of an
      effect of lactation-induced metabolic stress on oocyte developmental competence
      in the postpartum dairy cow assessed in terms of morphological quality and
      ability to develop following in vitro fertilization.

PMID- 22365210
TI  - A linear programming model to optimize diets in environmental policy scenarios.
AB  - The objective was to develop a linear programming model to formulate diets for
      dairy cattle when environmental policies are present and to examine effects of
      these policies on diet formulation and dairy cattle nitrogen and mineral
      excretions as well as methane emissions. The model was developed as a minimum
      cost diet model. Two types of environmental policies were examined: a tax and a
      constraint on methane emissions. A tax was incorporated to simulate a greenhouse
      gas emissions tax policy, and prices of carbon credits in the current carbon
      markets were attributed to the methane production variable. Three independent
      runs were made, using carbon dioxide equivalent prices of $5, $17, and $250/t. A
      constraint was incorporated into the model to simulate the second type of
      environmental policy, reducing methane emissions by predetermined amounts. The
      linear programming formulation of this second alternative enabled the calculation
      of marginal costs of reducing methane emissions. Methane emission and manure
      production by dairy cows were calculated according to published equations, and
      nitrogen and mineral excretions were calculated by mass conservation laws.
      Results were compared with respect to the values generated by a base least-cost
      model. Current prices of the carbon credit market did not appear onerous enough
      to have a substantive incentive effect in reducing methane emissions and altering
      diet costs of our hypothetical dairy herd. However, when emissions of methane
      were assumed to be reduced by 5, 10, and 13.5% from the base model, total diet
      costs increased by 5, 19.1, and 48.5%, respectively. Either these increased costs
      would be passed onto the consumer or dairy producers would go out of business.
      Nitrogen and potassium excretions were increased by 16.5 and 16.7% with a 13.5%
      reduction in methane emissions from the base model. Imposing methane restrictions
      would further increase the demand for grains and other human-edible crops, which
      is not a progressive solution for an industry trying to be sustainable. However,
      these results might depend on the constraints and inputs used in our model (e.g.,
      feed prices), and more extensive analyses are required before they are used in
      policy development. The model structure was able to incorporate effects of
      environmental policies in diet formulation and it can assist dairy producers in
      meeting limits set by these policies. The model can also assist policy makers
      examining the effects of policies on the dairy production system.

PMID- 22365211
TI  - Manageable risk factors associated with the lactational incidence, elimination,
      and prevalence of Staphylococcus aureus intramammary infections in dairy cows.
AB  - Staphylococcus aureus intramammary infections (IMI) are a major cause of mastitis
      on farms worldwide. Incidence and elimination rates are the key determinants of
      prevalence of Staph. aureus, and risk factors associated with these rates must be
      identified, prioritized, and controlled to obtain long-term reduction in
      prevalence. The objectives of this study were to identify manageable risk factors
      associated with the lactational incidence, elimination, and prevalence of Staph.
      aureus IMI. A cohort of 90 Canadian dairy farms was recruited and followed in
      2007 and 2008. Quarter milk samples were collected repeatedly from a selection of
      cows, and bacteriological culture was realized to assess incidence, elimination,
      and prevalence of Staph. aureus IMI. Practices used on farms were measured using
      direct observations and a validated questionnaire. A linear regression model was
      used to explore the relationship between herd IMI prevalence and incidence and
      elimination rates. Multilevel logistic regression models were used to compute
      measures of associations between practices used on farms and IMI incidence,
      elimination, and prevalence. The herd incidence rate was the most important
      predictor of herd IMI prevalence: a reduction of the incidence rate equivalent to
      its interquartile range (0.011 new IMI/quarter-month) was associated with a
      prevalence reduction of 2.2 percentage points; in comparison, an equivalent
      increase of the elimination rate by its interquartile range (0.36 eliminated
      IMI/quarter-month) resulted in a prevalence reduction of 0.4 percentage points.
      Postmilking teat disinfection and blanket dry-cow therapy were already
      implemented by most herds. Most of the practices associated with Staph. aureus
      IMI incidence were related to milking procedures. Among these, wearing gloves
      during milking showed desirable associations with IMI incidence, elimination, and
      prevalence. Similarly, adequate teat-end condition and use of premilking teat
      disinfection were associated with lower IMI incidence and prevalence. The initial
      herd prevalence of Staph. aureus IMI was positively associated with subsequent
      IMI incidence. This indicates that, in some situations, an initial reduction of
      the pool of infected quarters could be justified. Some housing practices were
      associated with IMI incidence, elimination, or prevalence. The effects of these
      latter practices, however, were often influenced by specific cow characteristics
      such as parity or days in milk. These results highlight the importance of good
      milking practices to prevent Staph. aureus IMI acquisition and, therefore, reduce
      their prevalence.

PMID- 22365212
TI  - The association of serum metabolites in the transition period with milk
      production and early-lactation reproductive performance.
AB  - The objective was to examine the associations of peripartum concentrations of
      nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), and calcium with
      milk production in early lactation and pregnancy at the first artificial
      insemination (AI) across different management systems. Fifty-five Holstein
      freestall dairy herds located across the United States and Canada were visited
      weekly for blood sample collection from 2,365 cows. For each week of sampling
      (from wk -1 through wk 3 relative to calving) and for each metabolite, serum
      concentrations were dichotomized at various thresholds to identify the thresholds
      with the best negative associations with milk production and pregnancy at first
      AI. These thresholds were used to categorize the serum concentrations into higher
      and lower risk categories. Repeated-measures ANOVA and multivariable logistic
      regression were conducted for milk production and pregnancy at the first AI data,
      respectively, considering cow as the experimental unit and herd as a random
      effect. In the week before calving, serum NEFA >= 0.5 mEq/L, BHBA >= 600 MUmol/L,
      and calcium <= 2.1 mmol/L were associated with 1.6 to 3.2 kg/d milk loss across
      the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of
      NEFA and BHBA in wk 1 and 2 after calving (>= 0.7 and >= 1.0 mEq/L for NEFA, and
      >= 1,400 and >= 1,200 MUmol/L for BHBA), and low levels of calcium (<= 2.1
      mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the
      first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated
      with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4
      mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy
      at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low
      concentrations of calcium around parturition were associated with early lactation
      milk loss, and low calcium concentration around parturition was associated with
      impaired early lactation reproduction.

PMID- 22365213
TI  - Genetic merit for fertility traits in Holstein cows: I. Production
      characteristics and reproductive efficiency in a pasture-based system.
AB  - The objective of the present study was to characterize the phenotypic performance
      of cows with similar proportions of Holstein genetics, similar genetic merit for
      milk production traits, but with good (Fert+) or poor (Fert-) genetic merit for
      fertility traits. Specifically, we tested the hypothesis that cows with a
      negative estimated breeding value for calving interval would have superior
      fertility performance and would have detectable differences in body reserve
      mobilization and circulating concentrations of metabolic hormones and metabolites
      compared with cows that had a positive estimated breeding value for calving
      interval. For the duration of the study, cows were managed identically as a
      single herd in a typical grass-based, spring-calving production system. A total
      of 80 lactation records were available from 26 Fert+ and 26 Fert- cows over 2
      consecutive years (2008 and 2009). During yr 1, cows were monitored during a 20
      wk breeding season to evaluate reproductive performance. Milk production, body
      condition score (scale 1 to 5), body weight, grass dry matter intake, energy
      balance, and metabolic hormone and metabolite data were collected during both
      years. The Fert+ cows had greater daily milk yield (19.5 vs. 18.7 kg/d), shorter
      interval from calving to conception (85.6 vs. 113.8 d), and fewer services per
      cow (1.78 vs. 2.83). No difference between groups in grass dry matter intake,
      energy balance, or body weight was observed. The Fert+ cows maintained greater
      BCS during mid (2.84 vs. 2.74 units) and late lactation (2.82 vs. 2.73 units).
      Circulating concentrations of insulin-like growth factor-I were greater
      throughout the gestation-lactation cycle in Fert+ cows (148.3 vs. 128.2 ng/mL).
      The Fert+ cows also had greater circulating concentrations of insulin during the
      first 4 wk of lactation (1.71 vs. 1.24 MUIU/mL). Analysis of records from
      national herd data verified the association between genetic merit for fertility
      traits and phenotypic reproductive performance; Fert+ cows (n = 2,436) required
      11.1 d less to recalve than did Fert- cows (n = 1,388), and the percentage of
      cows that successfully calved for the second time within 365 and 400 d of the
      first calving was 8 and 13% greater for Fert+ compared with Fert- cows,
      respectively. These results demonstrate that genetic merit for fertility traits
      had a pronounced effect on reproductive efficiency, BCS profiles, and circulating
      concentrations of insulin-like growth factor-I.

PMID- 22365214
TI  - Effects of monensin on metabolic parameters, feeding behavior, and productivity
      of transition dairy cows.
AB  - The effects of monensin on transition cow metabolism may be dependent on
      modulation of feeding behavior, rumen pH, and expression of key metabolic genes.
      Multiparous Holstein cows were used to determine the effects of monensin
      (400mg/cow daily) on these variables. Cows were randomly assigned, based on
      calving date, to control or monensin treatments (n = 16 per treatment) 21 d
      before their expected calving date, and cows remained on treatments through 21 d
      postpartum. Feeding behavior and water intake data were collected daily. Liver
      biopsies were conducted after assessing BCS and BW on d -21, -7, 1, 7, and 21
      relative to calving for analysis of triglyceride (TG) content as well as mRNA
      abundance of cytosolic phosphoenolpyruvate carboxykinase, carnitine
      palmitoyltransferase 1a, and apolipoprotein B. Blood samples were collected 21,
      7, and 4 d before expected calving and 1 (day of calving), 4, 7, 14, and 21 d
      postpartum for nonesterified fatty acid, beta-hydroxybutyrate, glucose, insulin,
      and haptoglobin analyses. Ruminal pH was collected every 5 min on d 1 through 6
      postpartum via a wireless indwelling probe. On d 7 postpartum, a caffeine
      clearance test was performed to assess liver function. Data were analyzed using
      mixed models with repeated measures over time. Monensin decreased mean plasma
      beta-hydroxybutyrate (734 vs. 616 +/- 41 MUM) and peak concentrations (1,076 vs.
      777 +/- 70 MUM on d 4 postpartum). Monensin also decreased time between meals
      prepartum (143 vs. 126 +/- 5.0 min) and postpartum (88.8 vs. 81.4 +/- 2.9 min),
      which was likely related to a smaller ruminal pH standard deviation in the first
      day after cows changed to a lactation ration (0.31 vs. 0.26 +/- 0.015). Monensin
      also increased liver mRNA abundance of carnitine palmitoyltransferase 1a (0.10
      vs. 0.15 +/- 0.002 arbitrary units), which corresponded to a slower rate of liver
      TG accumulation from d -7 to +7 (412 vs. 128 +/- 83 mg of TG/g of protein over
      this time period). No significant effects of monensin supplementation were
      observed on milk production, liver cytosolic phosphoenolpyruvate carboxykinase,
      apolipoprotein B, plasma nonesterified fatty acid, glucose, insulin, or
      haptoglobin. No effects on disease incidence were detected, but sample size was
      small for detecting such effects. Overall, results confirm that the effects of
      monensin on transition cows extend beyond altered propionate flux.

PMID- 22365215
TI  - The effect of stocking rate and calving date on reproductive performance, body
      state, and metabolic and health parameters of Holstein-Friesian dairy cows.
AB  - Two groups of Holstein-Friesian dairy cows with different mean calving dates (CD)
      were established from within the existing research herd at Moorepark (Teagasc,
      Ireland). Animals were assigned to either an early calving (mean CD February 12)
      treatment or a late calving (mean CD February 25) treatment. Animals within each
      CD treatment were randomly allocated to 1 of 3 stocking rate (SR) treatments, low
      (2.51 cows/ha), medium (2.92 cows/ha), or high (3.28 cows/ha), which were
      designed to represent 3 alternative whole-farm SR in a spring-calving, grass
      based milk production system following abolition of the European Union milk
      quotas. A total of 138 spring-calving dairy cows, comprising 2 strains of
      Holstein-Friesian, North American (NA) and New Zealand (NZ), were used in each
      year (2009 and 2010). The effects of CD, SR treatment, genetic strain, and their
      interactions on reproductive performance, body weight, body condition score,
      blood metabolites, hormone and immunological parameters, and health status were
      analyzed. Stocking rate and CD had no effect on pregnancy rates, immunological
      parameters, or health status, although a tendency was observed for more
      reproductive intervention as SR increased. Earlier calving and increased SR also
      resulted in reduced body weight, body condition score, and metabolic status in
      early lactation. Strain of Holstein-Friesian also affected reproductive
      performance. The NZ strain tended to have a higher submission rate and 42 d
      pregnancy rate compared with the NA strain, and a strain by SR interaction was
      observed for pregnancy rate to first service. Earlier calving and increased SR
      can be achieved without adverse effects on overall pregnancy rates. The existence
      of a SR by strain interaction for several reproductive variables suggests that
      the smaller NZ strain is better adapted to increased SR systems.

PMID- 22365216
TI  - A novel diagnostic technique to determine uterine health of Holstein cows at 35
      days postpartum.
AB  - The objectives were (1) to evaluate the association of uterine lavage sample
      optical density (ULSOD) with uterine health, and (2) to estimate and evaluate a
      threshold value that will maximize the accuracy of ULSOD as a diagnostic tool for
      clinical endometritis. The study enrolled 1,742 cows from 3 dairy farms located
      near Ithaca, New York. The samples were collected at 35 +/- 3 d in milk (DIM) by
      using low-volume uterine lavage. Cows with a purulent or mucopurulent secretion
      in the sample were diagnosed with clinical endometritis, whereas a subgroup of
      all studied cows was examined for cytological evidence of inflammation by
      endometrial cytology. Data for ULSOD measured at different wavelengths (200, 352,
      620, 790, 860, and 960 nm) were available for 554 cows; all 1,742 cows had data
      for ULSOD measured at 620 nm (ULSOD(620)). Incidences of clinical endometritis,
      metritis, and retained placenta were 10, 15.2, and 5.6%, respectively. The
      ULSOD(620) was associated with clinical endometritis. Receiver operating
      characteristic (ROC) analysis of the accuracy of optical density in the detection
      of clinical endometritis was conducted for ULSOD measured at different
      wavelengths; ULSOD(620) was selected for further analysis because it presented
      the best ROC curve to detect clinical endometritis. The recommended threshold for
      ULSOD(620) ROC was 0.058, where the sensitivity and specificity were 76.3 and
      78.3%, respectively. The ROC analysis of the accuracy of optical density in the
      detection of endometritis defined as a percentage of neutrophils in the uterine
      lavage samples higher than 18% was conducted for ULSOD(620). The recommended
      threshold was 0.059, where the sensitivity and specificity were 100 and 82.2%,
      respectively. Cows with ULSOD(620) <= 0.058 were 1.21 times more likely to
      conceive than cows with ULSOD(620) >0.058; moreover, the median calving-to
      conception interval for cows that had ULSOD(620) <= 0.058 was 122 d compared with
      148 d for cows that had ULSOD(620) >0.058. Cows that were positive for
      Arcanobacterium pyogenes, diagnosed with metritis, or had retained placenta had
      4.0, 1.4, and 1.7 times higher odds of having ULSOD(620) >0.058, respectively.
      Cows with ULSOD(620) >0.058 had a higher percentage of neutrophils in the uterine
      lavage samples than cows with ULSOD(620) <= 0.058. Uterine lavage sample optical
      density measured at 620 nm can be used as an objective indicator of uterine
      health in dairy cows, principally for clinical endometritis.

PMID- 22365217
TI  - Milk production and somatic cell counts: a cow-level analysis.
AB  - The objectives of this study were to quantify the relationship between 24-h milk
      loss and lactation milk loss due to mastitis at the cow level. For the year 2009,
      individual cow test-day production records from 2,835 Ontario dairy herds were
      examined. Each record consisted of 24-h milk and component yields, stage of
      lactation (days in milk, DIM), somatic cell count (SCC, *10(3) cells/mL) and
      parity. The modeling was completed in 2 stages. In stage 1, for each animal in
      the study, the estimated slope from a linear regression of 24-h milk yield (kg),
      adjusted for DIM, the quadratic effect of DIM, and the 24-h fat yield (kg) on
      ln(SCC) was determined. In stage 2, the estimated slope were modeled using a
      mixed model with a random component due to herd. The fixed effects included
      season (warm: May to September, cool: October to April), milk quartile class [MQ,
      determined by the rank of the 24-h average milk yield (kg) over a lactation
      within the herd] and parity. The estimated slopes from the mixed model analysis
      were used to estimate 24-h milk loss (kg) by comparing to a referent healthy
      animal with an SCC value of 100 (*10(3) cells/mL) or less. Lactation milk loss
      (kg) was then estimated by using estimated 24-h milk loss within lactation by
      means of a test-day interval method. Lactation average milk loss (kg) and SCC
      were also estimated. Lastly, lactation milk loss (kg) was modeled on the log
      scale using a mixed model, which included the random effect of herd and fixed
      effects, parity, and the linear and quadratic effect of the number of 24-h test
      days within a lactation where SCC exceeded 100 (*10(3) cells/mL; S100). The
      effect of SCC was significant with respect to 24-h milk loss (kg), increasing
      across parity and MQ. In general, first-parity animals in the first MQ (lower
      milk yield animals) were estimated to have 45% less milk loss than later parity
      animals. Milk losses were estimated to be 33% less for animals in first parity
      and MQ 2 through 4 than later parity animals in comparable MQ. Therefore, the
      relative level of milk production was found to be a significant risk factor for
      milk loss due to mastitis. For animals with 24-h SCC, values of 200 (*10(3)
      cells/mL), 24-h milk loss ranged from 0.35 to 1.09 kg; with 24-h SCC values of
      2,000 (*10(3) cells/mL), milk loss ranged from 1.49 to 4.70 kg. Lactation milk
      loss (kg) increased significantly as lactation average SCC increased, ranging
      from 165 to 919 kg. The linear and quadratic effect of S100 was a significant
      risk factor for lactation milk loss (kg), where greatest losses occurred in
      lactations with 5 or more 24-h test days where SCC exceeded 100 (*10(3)
      cells/mL).

PMID- 22365218
TI  - Short communication: Prevalence and risk factors of subclinical mastitis as
      determined by the California Mastitis Test in water buffaloes (Bubalis bubalis)
      in Nueva Ecija, Philippines.
AB  - A retrospective analysis using records of lactating Bulgarian Murrah buffaloes
      subjected to the California Mastitis Test in a herd in Nueva Ecija, Philippines
      was done to determine the prevalence of subclinical mastitis (SCM) and to
      identify risk factors that may influence its occurrence and recurrence. Results
      showed that SCM prevalence was 42.76%, whereas its recurrence was 75.03%. Age and
      lactation length influenced the occurrence of SCM. In contrast to the conclusions
      for dairy cows, younger buffalo cows were more susceptible compared with those at
      least 6 yr old. Dams younger than 3 yr have a 76% probability, whereas those age
      3 yr have an 82% probability of having SCM.

PMID- 22365219
TI  - Short communication: Prepartum plasma insulin-like growth factor-I concentrations
      based on day of insemination are lower in cows developing postpartum diseases.
AB  - Because peripartal production diseases are prevalent in dairy cows, early
      recognition is crucial. Several studies reported metabolic variables as risk
      predictors for subsequent diseases. To improve on-farm testing and application of
      those methods, the sampling procedure should take into account variation in
      gestation length. Furthermore, additional variables indicating cows at risk of
      any production disease should be sought. Therefore, the objective was to
      characterize differences between cows with and without postpartum production
      disease (retained fetal membranes, ketosis, hypocalcemia, abomasal displacement,
      metritis, mastitis) by prepartum measurement of serum nonesterified fatty acid
      (NEFA) and plasma insulin-like growth factor (IGF)-I concentrations relative to
      the artificial insemination (AI) that established pregnancy. Blood was collected
      from 41 Holstein Friesian cows on 235 to 241, 242 to 248, 249 to 255, 256 to 262,
      263 to 269, 270 to 276, 277 to 283, and 284 to 290 d after AI. Health status was
      assessed daily for 3 wk after calving; 25 cows (66%) had at least one production
      disease. Cows developing postpartum diseases had higher mean serum NEFA
      concentrations (450 +/- 26 MUmol/L; mean +/- SE) and lower plasma IGF-I
      concentrations (78 +/- 6 ng/mL) prepartum compared with healthy cows (259 +/- 19
      MUmol/L and 117 +/- 8 ng/mL, respectively). In conclusion, because of substantial
      variation among cows in gestation length, blood samples should be collected and
      studies performed on risk prediction relative to AI rather than expected date of
      calving. As the somatotropic axis is one of the key regulators of metabolic
      adaption for onset of lactation, IGF-I might be a useful variable to
      differentiate between cows susceptible to production diseases and cows that are
      able to adapt adequately within the transition period and remain healthy.

PMID- 22365220
TI  - Short communication: Presence of G protein-coupled receptor 43 in rumen
      epithelium but not in the islets of Langerhans in cattle.
AB  - Volatile fatty acids (VFA) are the major products of microbial fermentation in
      the rumen. Besides serving as substrates for energy generation, VFA are known to
      stimulate rumen development, increase serum insulin and glucagon concentrations,
      and regulate gene expression in cattle and sheep. The mechanisms underlying these
      regulatory effects of VFA are unknown, but the recent discovery that VFA can bind
      to G protein-coupled receptor 43 (GPR43) and 41 (GPR41) suggests that the
      regulatory effects of VFA may be mediated by these receptors. As a step toward
      testing this possibility, we determined whether GPR43 was expressed in bovine
      rumen wall and the pancreatic islets of Langerhans. Polyclonal antibody against a
      bovine GPR43 peptide was generated. The specificity of the antibody for bovine
      GPR43 was confirmed by Western blot analysis of recombinant bovine GPR43 protein.
      Immunohistochemical analyses using this antibody revealed the presence of GPR43
      immunoreactive cells in the epithelium, but not in the other layers of cattle
      rumen wall. The same immunohistochemical analyses did not reveal GPR43
      immunoreactive cells in the islets of Langerhans or the surrounding exocrine
      tissue of cattle pancreas. These data support the possibility that the effect of
      VFA on rumen epithelial growth in cattle is directly mediated by GPR43 in the
      rumen epithelial cells and that the effect of VFA on pancreatic secretion of
      insulin and glucagon in cattle is unlikely to be directly mediated by GPR43.

PMID- 22365221
TI  - Characterization of the disappearance and formation of biohydrogenation
      intermediates during incubations of linoleic acid with rumen fluid in vitro.
AB  - Dietary unsaturated fatty acids are extensively hydrogenated in the rumen,
      resulting in the formation of numerous intermediates that may exert physiological
      effects and alter the fat composition of ruminant-derived foods. A batch culture
      method was used to characterize the hydrogenation of linoleic acid (LeA) by
      strained rumen fluid in vitro. Incubations (n = 5) were performed in 100-mL
      flasks maintained at 39  degrees C containing 400mg of grass hay, 50 mL of
      buffered rumen fluid, and incremental amounts of LeA (0, 1.0, 2.5, 5.0, or
      10.0mg) for 0, 1.5, 3.0, 4.5, 6.0, and 9.0 h. The fatty acid composition of flask
      contents was determined using complimentary silver-ion thin-layer chromatography,
      gas chromatography mass-spectrometry, and silver-ion high-performance liquid
      chromatography. Linoleic acid was extensively (98.1, 97.6, 98.0, and 89.8% for
      additions of 1.0, 2.5, 5.0, and 10.0mg of LeA, respectively) hydrogenated over
      time. Complete reduction of LeA to 18:0 was inhibited in direct relation to the
      amount of added substrate, the extent of which was greatest for the highest
      amount of LeA addition. Recoveries of 1.0, 2.5, 5.0, and 10.0mg of added LeA as
      18:0 averaged 73.6, 65.0, 57.3, and 10.7%, respectively. Incubation of
      incremental amounts of LeA resulted in a time-dependent accumulation of geometric
      isomers of 9,11 and 10,12 conjugated linoleic acid, several nonconjugated 18:2
      isomers, and a wide range of cis 18:1 and trans 18:1 intermediates. Several
      unusual intermediates including cis-6,cis-12 18:2; cis-7,cis-12 18:2; and cis
      8,cis-12 18:2, were found to accumulate in direct relation to the amount of added
      LeA, providing the first indications that hydrogenation of LeA by ruminal
      bacteria may also involve mechanisms other than hydrogen abstraction or
      isomerization of the cis-12 double bond. Fitting of single-pool, first-order
      kinetic models to experimental data indicated that the rate of LeA disappearance
      decreased with increases in substrate availability. Reduction of 18:1 and 18:2
      intermediates occurred at much lower rates compared with conjugated linoleic acid
      and nonconjugated 18:2 isomer formation. In conclusion, the extent of LeA
      biohydrogenation in vitro was shown to be time- and dose-dependent with evidence
      that LeA is hydrogenated by ruminal bacteria via several distinct metabolic
      pathways. The accumulation of several unusual 18:2 isomers indicates that
      biohydrogenation of LeA also proceeds via mechanisms other than isomerization of
      the cis-12 double bond.

PMID- 22365222
TI  - Effect of time duration of ruminal urea infusions on ruminal ammonia
      concentrations and portal-drained visceral extraction of arterial urea-N in
      lactating Holstein cows.
AB  - The effects of a 6 versus 24h ruminal urea infusion in lactating dairy cows fed a
      basal diet deficient in N on ruminal ammonia concentration, arterial urea-N
      concentration, net portal-drained viscera (PDV) urea-N flux, arterial urea-N
      extraction across the PDV, and renal urea-N kinetics were investigated. Three
      Danish Holstein cows fitted with ruminal cannulas and permanent indwelling
      catheters in major splanchnic blood vessels were randomly allocated to a 3 * 3
      Latin square design with 21-d periods. Treatments were ventral ruminal infusion
      of water for 24h (water INF), 24-h infusion of 15 g of urea/kg of dry matter
      intake (DMI; 24-h INF), and 6-h infusion of 15 g of urea/kg of DMI (6-h INF). The
      6-h INF was initiated 0.5h after the afternoon feeding, and ran until 2230 h.
      Eight sample sets of arterial, portal, and hepatic blood, ruminal fluid, and
      urine were obtained at 0.5h before the morning feeding and 0.5, 1.5, 2.5, 3.5,
      4.5, 5.5, and 6.5h after feeding (i.e., 9 to 15.5h after the 6h infusion was
      terminated). A substantial decrease in DMI for 6-h INF compared with 24-h INF and
      water INF was observed, and it has to be recognized that DMI may have confounding
      effects. However, the experimental setting plan was met (i.e., to cause changes
      in the daily pattern of ruminal ammonia and blood urea-N concentrations). The
      arterial urea-N concentration for 24-h INF and 6-h INF were greater than the
      arterial urea-N concentration with water INF throughout the sampling window.
      However, the arterial urea-N concentration for 6-h INF decreased steadily with
      sampling time reflecting a carryover effect from the ruminal urea infusion. The
      ruminal ammonia concentration and net portal flux of ammonia for 6-h INF were not
      different from water INF; hence, no carryover effect on ruminal ammonia
      concentration was observed. The portal flux of urea-N was not affected by
      treatment (i.e., even the combination of low ruminal ammonia and high arterial
      urea-N concentration with 6-h INF was not used by the cow to increase the uptake
      of urea-N across the PDV). Arterial urea-N extraction across the PDV was
      increased with water INF especially from 0.5 to 3.5h postprandial relative to the
      urea infusion treatments, reflecting increased epithelial permeability for urea
      N. This indicates that daily ruminal peak of ammonia or blood urea-N
      concentrations overruled potential signals from low ruminal ammonia concentration
      observed during the sampling window. In conclusion, dairy cows appear unable to
      increase transport of urea-N from blood to gut in periods with low ruminal
      ammonia concentrations, even in a situation with infrequent N supply and apparent
      carryover effects on blood urea-N. It is speculated that mechanisms responsible
      for downregulation of epithelial urea-N transport based on daily maximum
      concentrations of ammonia in the rumen or urea-N in the blood suppresses any
      short-term signal from low ruminal ammonia during periods with low ruminal N
      supply.

PMID- 22365223
TI  - Prediction of immunoglobulin G content in bovine colostrum by near-infrared
      spectroscopy.
AB  - The objective of this work was to assess the potential of near infrared
      spectroscopy to predict the immunoglobulin G (IgG) content in bovine colostrum.
      Liquid colostrum samples (n=157) were collected from Holstein cows from 2 dairy
      farms in southern Chile. Samples were obtained within 1h of parturition and
      scanned in folded transmission (transflectance) in the visible-near infrared
      range. Multivariate regression models (modified partial least squares) were
      developed with spectral data against IgG content measured by radial
      immunodiffusion. The best calibration included a mathematical treatment of the
      spectra by a second derivative plus standard normal variate and detrending. The
      best equation explained a high proportion of the variation in IgG content (R(2)
      of 0.95 in calibration and 0.94 in cross-validation). Average (91.5 g/L),
      standard deviation (37.6g/L), and range, as highest minus lowest values (171.9
      g/L) of reference values were 10.1, 4.2, and 19 times the value of the root mean
      square error of cross-validation (9.03 g/L) respectively. Near-infrared
      spectroscopy, scanned in folded transmission, is an effective tool to predict the
      IgG content in liquid colostrum.

PMID- 22365224
TI  - A fibrolytic enzyme additive for lactating Holstein cow diets: ruminal
      fermentation, rumen microbial populations, and enteric methane emissions.
AB  - The objective was to determine if supplementing a dairy cow diet with an
      exogenous fibrolytic enzyme additive (Econase RDE; AB Vista, Marlborough,
      Wiltshire, UK) altered fermentation, pH, and microbial populations in the rumen
      or enteric methane (CH(4)) emissions. In a companion study, this enzyme additive
      improved efficiency of fat-corrected milk production in a dose-dependent manner
      by up to 11% for early lactation dairy cows. Nine ruminally cannulated, lactating
      Holstein cows were used in a replicated 3 * 3 Latin square design with 21-d
      periods. Dietary treatments were 0 (control), 0.5 (low), and 1.0 (high) mL of
      enzyme/kg of total mixed ration dry matter. Rumen contents were collected on 2 d
      (d 15 and 19), ruminal pH was measured continuously for 6 d (d 13 to 18) by using
      an indwelling system, and enteric CH(4) production was measured for 3 d (d 16 to
      18) using the sulfur hexafluoride tracer gas technique. The enzyme additive did
      not alter volatile fatty acids, NH(3), pH, or population densities of total
      protozoa, bacteria, and methanogens in ruminal fluid. However, population
      densities of certain bacteria, calculated as copy number of species-specific 16S
      rRNA, were affected by enzyme treatment. Population density of Ruminobacter
      amylophilus was increased and that of Fibrobacter succinogenes tended to be
      increased by the high enzyme treatment. Selenomonas ruminantium tended to
      increase linearly with increasing levels of enzyme in the diet, although its
      population density was only numerically increased by the high enzyme treatment.
      Streptococcus bovis, however, tended to be decreased by the low enzyme treatment.
      Increasing the level of enzyme supplement in the diet also linearly increased
      enteric CH(4) production, even when adjusted for feed intake or milk production
      (19.3, 20.8, and 21.7 g of CH(4)/kg of dry matter intake or 12.9, 13.6, and 15.1g
      of CH(4)/kg of milk for the control, low, and high enzyme treatments,
      respectively). This shift in ruminal bacterial communities and higher CH(4)
      emissions could imply increased ruminal digestion of feed, which needs to be
      substantiated in longer term studies.

PMID- 22365225
TI  - Effect of physical damage to ears of corn before harvest and treatment with
      various additives on the concentration of mycotoxins, silage fermentation, and
      aerobic stability of corn silage.
AB  - We studied the effects of damaging ears of corn in the field prior to harvest and
      the use of various additives on the production of selected mycotoxins, silage
      fermentation, and aerobic stability of whole plant corn. In experiment 1, ears of
      corn were undamaged or were slashed with a knife 7 d before harvesting, exposing
      damaged kernels to the environment. Corn plants were harvested (about 35% DM) and
      treated in a 2 * 2 factorial arrangement of treatments. Treatments were undamaged
      or damaged plants, untreated or treated with Lactobacillus buchneri 40788
      (400,000 cfu/g of fresh forage) and Pediococcus pentosaceus (100,000 cfu/g).
      Damaging ears prior to harvest increased the amount of fumonisin but decreased
      the amount of starch in harvested corn plants. After ensiling, corn silage made
      from plants damaged before harvest had lower starch but greater concentrations of
      deoxynivalenol and fumonisin than silage made from plants that were undamaged.
      Microbial inoculation resulted in fewer yeasts and lower concentrations of
      zearalenone in silage when compared to uninoculated silage. Inoculated silage
      also had more acetic acid and 1,2-propanediol than did uninoculated silage. In
      experiment 2, ears of corn were undamaged or were slashed with a knife 27 d or 9
      d before harvesting for corn silage. Whole plants were harvested at about 36% DM
      in a 2 * 3 factorial arrangement of treatments. Factors were time of damaging the
      ears (27 d, 9 d, or no damage) relative to harvest and no additive or 0.1% (fresh
      weight) potassium sorbate. Damaging plants 9 d prior to harvest did not affect
      the concentrations of deoxynivalenol, fumonisin, and zearalenone in plants at
      harvest. However, concentrations of deoxynivalenol and fumonisin were increased
      in fresh forage that had ears damaged at 27 d when compared to corn plants that
      were undamaged. Corn plants damaged for 27 d prior to harvest also had a lower
      concentration of starch than corn damaged for 9 d but was higher in acid
      detergent fiber than other treatments. The addition of potassium sorbate at
      harvest had no effect on the concentrations of mycotoxins in the resulting
      silage, but concentrations of mycotoxins were still greatest in silage made from
      plants that were damaged the longest prior to harvest (27 d). Silages treated
      with potassium sorbate had fewer yeasts and molds than silages without the
      additive. Damaging ears of corn before harvest had no effects on the aerobic
      stability of silages in both experiments. In contrast, the addition of the
      inoculant and potassium sorbate improved aerobic stabilities of silages when
      compared to untreated silages. These studies showed that physical damage to ears
      of corn prior to harvest can result in the production of mycotoxins in the field.
      This finding suggests that producers should test corn silage for mycotoxins prior
      to feeding especially if the forage has been subjected to physical damage prior
      to ensiling.

PMID- 22365226
TI  - An unprotected conjugated linoleic acid supplement decreases milk production and
      secretion of milk components in grazing dairy ewes.
AB  - Feeding conjugated linoleic acid (CLA) in a rumen-inert form to dairy ewes has
      been shown to increase milk production, alter milk composition, and increase the
      milk fat CLA content. However, few studies have tested ruminally unprotected CLA
      sources. The objective of this study was to evaluate the effects of an
      unprotected CLA supplement (29.8% of cis-9,trans-11 and 29.9% of trans-10,cis-12
      isomers as methyl esters) on milk yield and composition of dairy ewes. Twenty
      four lactating Lacaune ewes were used in a crossover design and received 2
      dietary treatments: (1) control: basal diet containing no supplemental lipid and
      (2) basal diet plus CLA (30 g/d). The CLA supplement was mixed into the
      concentrate and fed in 2 equal meals after morning and afternoon milkings. Each
      experimental period consisted of 21 d: 7 d for adaptation and 14 d for data
      collection. The CLA supplement decreased milk fat content and yield by 31.3 and
      38.0%, respectively. Milk yield and secretion of milk lactose and protein were
      decreased by 8.0, 9.8, and 5.6%, respectively. On the other hand, milk protein
      content and linear SCC score were 1.8 and 17.7% higher in ewes fed the CLA
      supplement. The concentration of milk fatty acids originating from de novo
      synthesis (<C16) was decreased by 25%, whereas the concentration of milk fatty
      acids taken up preformed from the plasma (>C16) was increased by 22.6% in ewes
      fed the CLA supplement. The CLA supplement decreased C14:1/C14:0, C16:1/C16:0,
      and C18:1/C18:0 desaturase indexes by 25, 18.7, and 0.1%, respectively, but
      increased the cis-9,trans-11 CLA/trans-11 C18:1 ratio by 8.6%. The concentrations
      of trans-10,cis-12 CLA and cis-9,trans-11 CLA in milk fat was 309 and 33.4%
      higher in ewes fed CLA. Pronounced milk fat depression coupled with the
      deleterious effects on milk yield, milk SCC, and secretion of all milk solids
      observed in ewes fed an unprotected CLA supplement is likely to be associated
      with high doses of trans-10,cis-12 CLA reaching the mammary gland, corroborating
      previous results obtained with dairy cows.

PMID- 22365227
TI  - Effect of dietary fat blend enriched in oleic or linoleic acid and monensin
      supplementation on dairy cattle performance, milk fatty acid profiles, and milk
      fat depression.
AB  - The effect of feeding increasing levels of oleic and linoleic acid both
      independently and together, with or without monensin, on milk fat depression was
      evaluated. Fifty-six Holstein cows were blocked by parity and then were divided
      by milk production into 2 groups (high or low) of 14 cows each within each parity
      block. A cow pair of 1 high and 1 low production cow within each parity block was
      fed in a single electronic feeding gate. Gates (n = 28) were considered the
      experimental unit and were assigned to monensin (17.5 g/t of dry matter) or
      control as the main plot (n = 14 each). The 7 cow pairs in each of the fixed
      effect groups were further assigned to a sequence of fat blend diets as split
      plot. Seven fat blend treatments in the split plot 7 * 7 Latin square were no
      added fat (no fat) and diets with increasing levels of oleic or linoleic acid:
      low C18:1 + low C18:2 (LOLL); low C18:1 + medium C18:2 (LOML); low C18:1 + high
      C18:2 (LOHL); medium C18:1 + low C18:2 (MOLL); medium C18:1+medium C18:2 (MOML);
      and high C18:1+low C18:2 (HOLL). Monensin feeding did not affect milk yield or
      concentration and yield of milk fat. Feeding monensin decreased the proportion of
      C <16, increased the proportion of total C18, increased the proportion and yield
      of trans-10 C18:1, and increased the proportion of trans-10,cis-12 conjugated
      linoleic acid in milk fatty acids (FA). As dietary C18:1 or C18:2 increased
      beyond the concentration present in LOLL, milk fat concentration, milk fat yield,
      and proportion and yield of milk C <16 all decreased, and the proportion and
      yield of milk trans-10 C18:1 increased. A quadratic effect on milk fat
      concentration and yield was noticed for C18:2 feeding, but not for C18:1 feeding.
      When dietary contents of total FA and FA other than C18:1 and C18:2 were similar,
      C18:2-rich diets decreased milk fat concentration and yield compared with C18:1
      rich diets (LOML vs. MOLL, and LOHL vs. HOLL), indicating that C18:2 is more
      potent than C18:1 for depressing milk fat. Increasing dietary FA content from no
      fat to LOLL, which increased primarily C18:1 and C18:2 with small increases in
      C18:0 and C16:0, decreased the secretion of C <16 but increased total C18
      secretion in milk. This suggests that biohydrogenation intermediates act to
      decrease mammary FA synthesis at low levels of added C18:1 and C18:2. No
      significant monensin * fat interactions were detected for the milk composition
      parameters analyzed; however, a monensin * fat interaction was found for milk fat
      trans-10 C18:1 proportion.

PMID- 22365228
TI  - Measuring residual feed intake in dairy heifers fed an alfalfa (Medicago sativa)
      cube diet.
AB  - Selection for divergence between individuals for efficiency of feed utilization
      (residual feed intake, RFI) has widespread application in the beef industry and
      is usually undertaken when animals are fed diets based on silages with grain. The
      objective of this research was to develop a feeding system (using Gallagher,
      Hamilton, New Zealand, electronics) to measure RFI for growth in Holstein
      Friesian heifers (aged 5-9 mo), and identify divergent individuals to be tested
      for RFI during lactation. A dry forage diet (alfalfa cubes) was fed because
      intakes could be measured accurately, and the New Zealand dairy industry (4.4
      million milking cows in lactation) relies heavily on forage feeding. The
      evaluation was undertaken over 3 yr with 1,052 animals fed in a facility for 7
      wk, and weighed 3 times weekly. The mean age at the start of measurements was 215
      d, body weight (BW) 189 kg, and mean daily dry matter intakes averaged 6.7 kg.
      Body weight gain (all animals) averaged 0.88 kg/d. The RFI was determined as the
      residuals from the regression of mean intake on mean BW(0.75) and daily BW gain
      of individuals. Actual and fitted intakes were strongly related (R(2) = 0.82). In
      terms of gross efficiency (feed intake/BW gain), RFI+year explained 43% of the
      variation, BW gain+year explained 66%, and RFI+BW gain+year explained 79% of the
      variation (all P<0.001). Daily BW gains (kg) of the most and least efficient 10%
      averaged (+/- standard deviation) 0.88 +/- 0.15 and 0.88 +/- 0.12 (P = 0.568),
      respectively, and the divergence between mean intakes was 1.46 kg of dry
      matter/d. The most and least efficient animals will be tested for RFI during
      lactation and genetic markers will be identified for the trait.

PMID- 22365229
TI  - Effect of corn silage harvest maturity and concentrate type on milk fatty acid
      composition of dairy cows.
AB  - The variation in maturity at harvest during grain filling has a major effect on
      the carbohydrate composition (starch:NDF ratio) and fatty acid (FA) content of
      corn silages, and can alter the FA composition of milk fat in dairy cows. This
      study evaluated the effect of silage corn (cv. Atrium) harvested and ensiled at
      targeted DM contents of 300, 340, 380, and 420 g/kg of fresh weight and fed to
      dairy cows in combination with a highly degradable carbohydrate (HC) or low
      degradable carbohydrate concentrate, on the nutrient intake, milk yield, and
      composition of milk and milk fat. Sixty-four multiparous Holstein-Friesian dairy
      cows in their first week of lactation were assigned to the 8 dietary treatments
      according to a randomized complete block design. The 8 dietary treatments
      consisted of a factorial combination of the 4 corn silages and the 2
      concentrates. Corn silages were offered ad libitum as part of a basal forage
      mixture, whereas the concentrates were given at the rate of 8.5 kg of DM/cow per
      day during the 15-wk experimental period. Dry matter, crude protein, and energy
      intakes did not differ across the corn silages. However, the intake of starch
      increased, and those of NDF and C18:3n-3 decreased with increasing maturation.
      Milk yield and composition were not different across the corn silages. Yield
      (kg/d) of milk, protein, and lactose was higher for low-degradable carbohydrate
      compared with HC concentrate-fed groups. Increasing maturity of corn silages
      decreased the content of C18:3n-3 and total n-3 and increased the n-6:n-3 ratio
      in milk fat. Concentrate type significantly altered the composition of all trans
      FA, except C18:2 trans-9,12. Inclusion of the HC concentrate in the diets
      increased the contents of all C18:1 trans isomers, C18:2 cis-9,trans-11, and
      C18:2 trans-10,cis-12 conjugated linoleic acid in milk fat. Milk fat composition
      was strongly influenced by the stage of lactation (wk 3 to 10). The content of
      all even short- and medium-chain FA changed with lactation, except C8:0 and
      C10:0. The content of C12:0, C14:0, and C16:0 and total saturated FA increased
      and the content of C18:0, C18:1 cis total, and total cis monounsaturated FA
      decreased with lactation. Maturity of the corn silages at harvest did not affect
      the production performance of dairy cows, but resulted in a decreased content of
      C18:3n-3, total n-3, and an increased n-6:n-3 ratio in the milk fat of dairy
      cows.

PMID- 22365230
TI  - Comparison of effects of dietary coconut oil and animal fat blend on lactational
      performance of Holstein cows fed a high-starch diet.
AB  - Dietary medium-chain fatty acids (C(8:0) through C(12:0)) are researched for
      their potential to reduce enteric methane emissions and to increase N utilization
      efficiency in ruminants. We aimed to 1) compare coconut oil (CNO; ~60% medium
      chain fatty acids) with a source of long-chain fatty acids (animal fat blend;
      AFB) on lactational responses in a high-starch diet and 2) determine the effect
      of different dietary concentrations of CNO on dry matter intake (DMI). In
      experiment 1, the control diet (CTRL) contained (dry basis) 40% forage (71% corn
      silage, and alfalfa hay and haylage), 26% NDF, and 35% starch. Isonitrogenous
      treatment diets contained 5.0% of AFB (5%-AFB), CNO (5%-CNO), or a 1-to-1 mixture
      of AFB and CNO (5%-AFB-CNO) and 0.8% corn gluten meal in place of corn grain.
      Thirty-two multiparous dairy cows (201 +/- 46 d postpartum; 42.0 +/- 5.5 kg/d
      3.5% fat-corrected milk yield) were adapted to CTRL, blocked by milk yield, and
      randomly assigned to 1 of 4 treatment diets for 21 d with samples and data
      collected from d 15 through 21. Treatment 5%-CNO decreased DMI markedly and
      precipitously and was discontinued after d 5. In wk 3, 5%-AFB and especially 5%
      AFB-CNO lowered total-tract NDF digested vs. CTRL (2.6 vs. 1.8 vs. 3.1 kg/d,
      respectively), likely because fat treatments reduced DMI and 5%-AFB-CNO impaired
      total-tract NDF digestibility. Milk fat concentrations were 3.10% (CTRL), 2.51%
      (5%-AFB), and 1.97% (5%-AFB-CNO) and correlated negatively to concentrations of
      C(18:2 trans-10,cis-12) in milk fat. Additionally, 5%-AFB and 5%-AFB-CNO tended
      to lower milk yield and decreased yields of solids-corrected milk and milk
      protein compared with CTRL. Fat treatments decreased milk lactose concentration,
      but increased milk citrate concentration. Moreover, cows fed 5%-AFB-CNO produced
      less solids-corrected milk than did cows fed 5%-AFB. In experiment 2, diets
      similar to CTRL contained 2.0, 3.0, or 4.0% CNO. Fifteen multiparous cows (219 +/
      42 d postpartum; 42.1 +/- 7.0 kg milk yield; mean +/- SD) were blocked by DMI
      and randomly assigned to 1 of 3 treatment diets for an 8-d evaluation. Dietary
      concentration of CNO affected DMI, with the greatest depression at 4.0% CNO.
      Overall, dietary CNO depressed DMI and NDF digestibility of a high-starch diet
      compared with AFB. Feeding CNO to lactating cows equal to or greater than 2.5%
      decreased lactational performance or DMI.

PMID- 22365231
TI  - Establishment of ruminal enzyme activities and fermentation capacity in dairy
      calves from birth through weaning.
AB  - The objectives of this study were to characterize the establishment of ruminal
      fermentation and enzymatic activities in dairy calves from birth to weaning (d
      83). Six Holstein calves, immediately separated from their mother at birth, were
      fed colostrum for 3 d after birth, and thereafter milk replacer, starter pelleted
      concentrate, and hay until d 83 of age. Ruminal samples were collected from each
      calf every day for the first 10 d, and additionally at d 12, 15, 19, 22, 26, 29,
      33, 36, 40, 43, 47, 50, 55, 62, 69, and 83. Ruminal samples were collected 1h
      after milk feeding with a stomach tube. The pH and redox potential (E(h)) were
      immediately measured. Samples were kept for further determination of ammonia
      nitrogen (NH(3)-N) and volatile fatty acid (VFA) concentrations, and xylanase,
      amylase, urease, and protease activities. Ruminal pH averaged 6.69, 5.82, and
      6.34, from d 1 to 9, d 10 to 40, and d 43 to 83 of age, respectively. At first
      day of life, the ruminal E(h) value was positive (+224 mV). From d 2 to 9, d 10
      to 40, and d 43 to 83 of age, ruminal E(h) averaged -164, -115, and -141 mV,
      respectively. From d 1 to 3, d 4 to 22, and d 26 to 83 of age, NH(3)-N
      concentration averaged 60.1, 179.8, and 58.2 mg/L, respectively. No VFA were
      detected in ruminal samples collected on d 1 of life of calves. From d 2 to 10
      and d 12 to 83 of age, ruminal total VFA concentration averaged 19.5 and 84.4mM,
      respectively. Neither ruminal xylanase or amylase activities were observed at d 1
      of age. From d 5 to 15 and d 19 to 83 of age, the xylanase activity averaged
      182.2 and 62.4 MUmol of sugar released per hour per gram of ruminal content dry
      matter (DM), respectively. From d 5 to 83 of age, the amylase activity reached
      35.4 MUmol of sugar released per hour per gram of ruminal content DM. The ruminal
      ureolytic activity was observed with an average value of 6.9 MUg of NH(3)-N
      released per minute per gram of ruminal content DM over the 83-d experimental
      period. From d 1 to 4 and d 5 to 83 of age, the proteolytic activity was 8.2 and
      27.9 optical density units per hour per gram of ruminal content DM, respectively.
      The fermentative and enzymatic activities were rapidly established in the rumen
      from d 2 after birth. Most parameters did not evolve further after 1 mo of age.

PMID- 22365232
TI  - Comparison and improvements of different Bayesian procedures to integrate
      external information into genetic evaluations.
AB  - The aim of this research was to compare different Bayesian procedures to
      integrate information from outside a given evaluation system, hereafter called
      external information, and in this context estimated breeding values (EBV), into
      this genetic evaluation, hereafter called internal evaluation, and to improve the
      Bayesian procedures to assess their potential to combine information from diverse
      sources. The 2 improvements were based on approximations of prior mean and
      variance. The first version of modified Bayesian evaluation considers all animals
      as animals associated with external information. For animals that have no
      external information (i.e., internal animals), external information is predicted
      from available external information. Thereby, propagation of this external
      information through the whole pedigree is allowed. Furthermore, the prediction of
      external information for internal animals allows large simplifications of the
      computational burden during setup and solving of mixed model equations. However,
      double counting among external animals (i.e., animals associated with available
      external information) is not avoided. Double counting concerns multiple
      considerations of contributions due to relationships by integration of external
      EBV for related external animals and is taken into account by the second version
      of modified Bayesian evaluation. This version includes the estimation of double
      counting before integration of external information. To test the improvements, 2
      dairy cattle populations were simulated across 5 generations. Milk production for
      the first lactation for each female was simulated in both populations. Internal
      females were randomly mated with internal males and 50 external males. Results
      for 100 replicates showed that rank correlations among Bayesian EBV and EBV based
      on the joint use of external and internal data were very close to 1 for both
      external and internal animals if all internal and external animals were
      associated with external information. The respective correlations for the
      internal evaluation were equal to 0.54 and 0.95 if no external information was
      integrated. If double counting was avoided, mean squared error, expressed as a
      percentage of the internal mean squared error, was close to zero for both
      external and internal animals. However, computational demands increased when
      double counting was avoided. Finally, the improved Bayesian procedures have the
      potential to be applied for integrating external EBV, or even genomic breeding
      values following some additional assumptions, into routine genetic evaluations to
      evaluate animals more reliably.

PMID- 22365233
TI  - Food intake, milk production, and tissue changes of Holstein-Friesian and Jersey
      * Holstein-Friesian dairy cows within a medium-input grazing system and a high
      input total confinement system.
AB  - Although interest in crossbreeding within dairy systems has increased, the role
      of Jersey crossbred cows within high concentrate input systems has received
      little attention. This experiment was designed to examine the performance of
      Holstein-Friesian (HF) and Jersey * Holstein-Friesian (J * HF) cows within a high
      concentrate input total confinement system (CON) and a medium concentrate input
      grazing system (GRZ). Eighty spring-calving dairy cows were used in a 2 (cow
      genotype) * 2 (milk production system) factorial design experiment. The
      experiment commenced when cows calved and encompassed a full lactation. With GRZ,
      cows were offered diets containing grass silage and concentrates [70:30 dry
      matter (DM) ratio] until turnout, grazed grass plus 1.0 kg of concentrate/day
      during a 199-d grazing period, and grass silage and concentrates (75:25 DM ratio)
      following rehousing and until drying-off. With CON, cows were confined throughout
      the lactation and offered diets containing grass silage and concentrates (DM
      ratio; 40:60, 50:50, 40:40, and 75:25 during d 1 to 100, 101 to 200, 201 to 250,
      and 251 until drying-off, respectively). Full-lactation concentrate DM intakes
      were 791 and 2,905 kg/cow for systems GRZ and CON, respectively. Although HF cows
      had a higher lactation milk yield than J * HF cows, the latter produced milk with
      a higher fat and protein content, so that solids-corrected milk yield (SCM) was
      unaffected by genotype. Somatic cell score was higher with the J * HF cows.
      Throughout lactation, HF cows were on average 37 kg heavier than J * HF cows,
      whereas the J * HF cows had a higher body condition score. Within each system,
      food intake did not differ between genotypes, whereas full-lactation yields of
      milk, fat plus protein, and SCM were higher with CON than with GRZ. A significant
      genotype * environment interaction was observed for milk yield, and a trend was
      found for an interaction with SCM. Crossbred cows on CON gained more body
      condition than HF cows, and overall pregnancy rate was unaffected by either
      genotype or management system. In summary, milk and SCM yields were higher with
      CON than with GRZ, whereas genotype had no effect on SCM. However, HF cows
      exhibited a greater milk yield response and a trend toward a greater SCM yield
      response with increasing concentrate levels compared with the crossbred cows.

PMID- 22365234
TI  - Genetic analysis of pathogen-specific clinical mastitis in Norwegian Red cows.
AB  - The objective of this study was to estimate heritabilities and genetic
      correlations for pathogen-specific clinical mastitis (CM) in Norwegian Red cows.
      In Norway, breeding values for mastitis are predicted based on records of
      veterinary treatments of clinical mastitis. Bacteriological milk sample results
      from the mastitis laboratories have been recorded routinely into the Norwegian
      Dairy Herd Recording System since 2000, but have so far not been used in genetic
      analyses. This additional source of data may provide valuable information on
      pathogen-specific CM. Records from 234,088 first-lactation Norwegian Red cows,
      daughters of 1,656 sires, were used for genetic analyses of unspecific,
      Staphylococcus aureus, Streptococcus dysgalactiae, and Escherichia coli CM. The 4
      CM traits were defined as binary and scored as 1 if the cow had at least 1 case
      of the CM in question and 0 otherwise. A Bayesian approach using Gibbs sampling
      was applied, and a multivariate threshold liability model was used for the
      analyses. The posterior mean (SD <= 0.01) of the heritabilities were 0.06 for
      liability of unspecific CM, 0.04 for Staph. aureus CM, 0.02 for Strep.
      dysgalactiae CM, and 0.03 for E. coli CM. The posterior mean (SD) of the genetic
      correlations were all high, ranging from 0.75 (0.14) to 0.87 (0.07). The highest
      genetic correlation was found between unspecific CM and Strep. dysgalactiae CM,
      whereas the lowest was found for E. coli CM and Staph. aureus CM. Genetic
      correlations lower than 1 indicate that mastitis caused by different pathogens
      can be considered as partly different traits. In spite of high rank correlations
      (0.95-0.98), some re-ranking of sires was observed.

PMID- 22365235
TI  - Use of the Illumina Bovine3K BeadChip in dairy genomic evaluation.
AB  - Genomic evaluations using genotypes from the Illumina Bovine3K BeadChip (3K)
      became available in September 2010 and were made official in December 2010. The
      majority of 3K-genotyped animals have been Holstein females. Approximately 5% of
      male 3K genotypes and between 3.7 and 13.9%, depending on registry status, of
      female genotypes had sire conflicts. The chemistry used for the 3K is different
      from that of the Illumina BovineSNP50 BeadChip (50K) and causes greater
      variability in the accuracy of the genotypes. Approximately 2% of genotypes were
      rejected due to this inaccuracy. A single nucleotide polymorphism (SNP) was
      determined to be not usable for genomic evaluation based on percentage missing,
      percentage of parent-progeny conflicts, and Hardy-Weinberg equilibrium
      discrepancies. Those edits left 2,683 of the 2,900 3K SNP for use in genomic
      evaluations. The mean minor allele frequencies (MAF) for Holstein, Jersey, and
      Brown Swiss were 0.32, 0.28, and 0.29, respectively. Eighty-one SNP had both a
      large number of missing genotypes and a large number of parent-progeny conflicts,
      suggesting a correlation between call rate and accuracy. To calculate a genomic
      predicted transmitting ability (GPTA) the genotype of an animal tested on a 3K is
      imputed to the 45,187 SNP included in the current genomic evaluation based on the
      50K. The accuracy of imputation increases as the number of genotyped parents
      increases from none to 1 to both. The average percentage of imputed genotypes
      that matched the corresponding actual 50K genotypes was 96.3%. The correlation of
      a GPTA calculated from a 3K genotype that had been imputed to 50K and GPTA from
      its actual 50K genotype averaged 0.959 across traits for Holsteins and was
      slightly higher for Jerseys at 0.963. The average difference in GPTA from the 50K
      and 3K-based genotypes across trait was close to 0. The evaluation system has
      been modified to accommodate the characteristics of the 3K. The low cost of the
      3K has greatly increased genotyping of females. Prior to the availability of the
      3K (August 2010), female genotyping accounted for 38.7% of the genotyped animals.
      In the past year, the portion of total genotypes from females across all chip
      types rose to 59.0%.

PMID- 22365236
TI  - Short communication: Interactions of milk, fat, and protein yield genotypes with
      herd feeding characteristics.
AB  - Data from 879 Holstein cows from 11 tie-stall herds in Pennsylvania were analyzed
      to determine the effects of nutritional management practices on the level of
      genetic expression for milk, fat, and protein yields. Environments were defined
      according to the amount of dry matter refusals at the end of 24h for the average
      cow (DMR), diet crude protein percentage (CP), and diet NE(L) concentration. Sire
      predicted transmitting ability (PTA) was available for all cows, whereas 775 cows
      were genotyped and received a molecular breeding value (MBV) for milk, fat, and
      protein yields. Milk, fat, and protein yields were regressed on sire PTA and cow
      MBV independently in addition to combined breeding values (CBV) of sire PTA and
      cow MBV. Four-trait animal models with fat-corrected milk yield in high and low
      environments plus either body weight or body condition score in high and low
      environments treated as separate traits were also evaluated. Regressions on sire
      PTA (0.31 for fat yield to 0.54 for milk yield) were significantly lower in the 5
      herds that had the lowest average DMR than in the 6 herds with highest average
      DMR (0.82 for fat yield to 1.11 for protein yield). The regressions of milk and
      protein yield on CBV were also significantly lower in the 5 herds with low NE(L)
      concentration in the ration than in herds that had high NE(L) concentration.
      Genetic correlations from animal models showed that large cows were more affected
      by low DMR, CP, and NE(L) concentration than smaller cows. Efforts to minimize
      feed wastage must ensure that cows receive adequate nutrient intake to avoid
      suppression of genetic potential for yield, particularly for larger cows.

PMID- 22365237
TI  - Short communication: Association of an OLR1 polymorphism with milk production
      traits in the Israeli Holstein population.
AB  - Previous studies have reported significant associations between haplotypes of the
      oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) gene and a
      single nucleotide polymorphism (SNP) in its 3'-untranslated region with milk
      composition and health traits in different cattle populations. However, to
      provide a better estimation of the impact and size of the association of OLR1
      with production traits, a need exists to validate its genomic association in
      additional cattle populations. Thus, the objective of this study was to perform
      association analysis of the OLR1 SNP with milk traits in the Israeli Holstein
      population. Estimated breeding values of milk composition traits and somatic cell
      score were obtained for a total of 1,211 Holstein cows, which were genotyped for
      a SNP in the 3'-untranslated region. Statistical analysis revealed significant
      association between the OLR1 SNP and protein percentage and somatic cell score.
      Thus, the validation of association of this SNP with milk traits in independent
      cattle populations suggests OLR1 as a candidate gene for further functional
      studies.

PMID- 22365238
TI  - Evaluation of various selective media for the detection of Pseudomonas species in
      pasteurized milk.
AB  - Pseudomonas spp. are common gram-negative, post-pasteurization contaminants that
      contribute to spoilage of pasteurized dairy products. This study evaluated 5
      common selective media for detecting Pseudomonas spp. in pasteurized milk. The
      performance of each selective medium for recovering 12 different Pseudomonas
      isolates (selected to represent a diversity of pasteurized milk isolates) was
      compared with that of standard plate count agar pour plates. Pseudomonas isolates
      showed varying abilities to produce colonies on different selective media. For 2
      of 12 isolates, a 48-h incubation time was required for colony formation on any
      of the media tested. Violet red bile agar and coliform Petrifilm (3M, St. Paul,
      MN) were less effective than standard plate count agar pour plates at recovering
      Pseudomonas, regardless of incubation time, and MacConkey agar showed poor
      detection efficiency compared with SPCP after a 48-h incubation (R(2) = 0.26).
      Therefore, the use of violet red bile agar, MacConkey agar, or coliform Petrifilm
      may not be sufficient for detecting common Pseudomonas spp. in milk. The methods
      showing the highest detection efficiencies were crystal violet tetrazolium agar
      (CVTA) pour plates (R(2) = 0.95) and CVTA plates inoculated by spiral plating
      (R(2) = 0.89) incubated at 32  degrees C for 48 h. Overall, plating milk samples
      on CVTA followed by a 48-h incubation at 32  degrees C was the most effective
      selective method for recovering a diversity of Pseudomonas spp. from milk.

PMID- 22365239
TI  - Lactating dairy cows adapt quickly to being milked by an automatic milking
      system.
AB  - Transitioning a dairy herd to an automatic milking system (AMS) from a
      conventional parlor system may be stressful for the cow, as many changes occur
      during this process. Chronic stress may affect the welfare of the cow, and acute
      stress during milking can decrease milk yield. Therefore, it is important to
      quantify if and how long stress during adaptation to an AMS might persist.
      Seventy-seven cows with acceptable udder and teat conformation that would not
      interfere with adaptation to the AMS and that were lactating n = 18, early [0 to
      100 d in milk (DIM)]; n = 27, mid (100 to 200 DIM); and n = 32, late (200+ DIM)
      for the full duration of the project were chosen for observation. All cows had
      been milked previously in a double-6 herringbone milking parlor. Four stress
      related behaviors [step-kick behavior both before and after attachment of teat
      cups, elimination (urination and defecation instances), and vocalization] were
      recorded during milking by trained observers, whereas milk yield was
      automatically recorded by the AMS. Data were collected for 24-h periods beginning
      on the day the cows transitioned to milking in the AMS (d 0), and on d 1, 2, 4,
      8, 16, and 32 thereafter. Instances of elimination and vocalization were greater
      on d 0 compared with all other days (elimination: d 0 = 3.1 +/- 0.09, d 1 = 0.6
      +/- 0.07, and 0 +/- 0 instances thereafter; vocalization: d 0 = 1.7 +/- 0.07, d 1
      = 0.05 +/- 0.04, and 0 +/- 0 instances thereafter). Milk yield increased between
      d 0 (18.3 +/- 1.7 kg) and d 1 (30.9 +/- 1.7 kg). Primiparous cows (n=28) were
      more likely than multiparous cows (n = 49) to display step-kick behaviors both
      before (8.3 +/- 2.5; 5.5 +/- 0.6, respectively) and after (15.6 +/- 2.4; 13.3 +/-
      1.3, respectively) teat cup attachment during milking. Eight days after
      introducing the cows to the AMS, over 60% of the herd was milking voluntarily and
      95% of the herd was milking voluntarily within a month, which suggests that cows
      did not find the AMS aversive. Greater elimination and vocalization behavior and
      lower milk yield on d 0 relative to subsequent days indicated initial stress and
      discomfort with the milking process in the new system; however, the cows appeared
      to adapt within 24h.

PMID- 22365240
TI  - Prevalence of plasmid-mediated quinolone resistance determinants qnr and aac(6')
      Ib-cr in Escherichia coli and Klebsiella pneumoniae producing extended-spectrum
      beta-lactamases in Spain.
AB  - The presence of the plasmid-mediated quinolone resistance determinants qnrA,
      qnrB, qnrS and aac(6')-Ib-cr was evaluated in a collection of 382 isolates of
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella
      pneumoniae collected between February and March 2006 for the nationwide Spanish
      GEIH-ESBL 2006 project. In total, 14 isolates (3.7%) were positive for qnr genes
      (3 qnrA1, 5 qnrB-like and 6 qnrS1) and 62 isolates (16.2%) were positive for the
      mutant variant of aac(6')-Ib-cr. The Aac(6')-Ib-cr enzyme was the most prevalent
      plasmid-mediated mechanism of quinolone resistance in Spain. Most of the Aac(6')
      Ib-cr-producing E. coli isolates (94.2%) carried two mutations in gyrA and two in
      parC, whilst only 57.2% of K. pneumoniae harbouring this enzyme were gyrA and/or
      parC mutants. Most qnr plasmids were transferable, but only four were
      conjugative. Plasmid incompatibility groups were identified for only four
      plasmids, belonging to FIA, HI2 and I1gamma. The most prevalent ESBLs associated
      with qnr plasmids belonged to the SHV and CTX-M families. The present study
      highlights the broad geographical spread of qnr-like determinants in Spain and
      their association with the SHV-12 and CTX-M-9 ESBLs in human clinical isolates.

PMID- 22365241
TI  - Approach to the diagnosis of interstitial lung disease.
AB  - Interstitial lung diseases (ILDs) encompass a wide range of diffuse pulmonary
      disorders, characterized by a variable degree of inflammatory and fibrotic
      changes of the alveolar wall and eventually the distal bronchiolar airspaces.
      ILDs may occur in isolation or in association with systemic diseases. The
      clinical evaluation of a patient with ILD includes a thorough medical history and
      detailed physical examination; obligatory diagnostic testing includes laboratory
      testing, chest radiography, and high-resolution computed tomography and
      comprehensive pulmonary function testing and blood gas analysis. To optimize the
      diagnostic yield, a dynamic interaction between the pulmonologist, radiologist,
      and pathologist is mandatory.

PMID- 22365242
TI  - Radiological approach to interstitial lung disease: a guide for the
      nonradiologist.
AB  - Articles in the past have described the radiological appearances of different
      interstitial lung diseases (ILDs) in varying levels of detail. However, these
      articles have generally been written for radiologists with a background in basic
      chest computed tomography (CT) interpretation. This article summarizes a basic
      approach for diagnosing ILDs on high-resolution CT (HRCT) for the nonradiologist
      clinician and discusses the most common HRCT features of common ILDs.

PMID- 22365243
TI  - Histopathologic approach to the surgical lung biopsy in interstitial lung
      disease.
AB  - Interpretation of lung biopsy specimens is an integral part in the diagnosis of
      interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy
      for disease involves answering several questions. Unlike much of surgical
      pathology of neoplastic lung disease, arriving at the correct diagnosis in
      nonneoplastic lung disease often requires correlation with clinical and
      radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers
      several hundred entities. This article is meant to be a launching point in the
      clinician's approach to the histologic evaluation of lung disease.

PMID- 22365244
TI  - Idiopathic pulmonary fibrosis: diagnosis and epidemiology.
AB  - In 2000, the American Thoracic Society and European Respiratory Society published
      the first consensus statement providing guidelines on the diagnosis and treatment
      of idiopathic pulmonary fibrosis (IPF). This statement presented, for the first
      time, diagnostic criteria for IPF and recommendations for treatment. Results from
      several studies have reshaped the thinking on IPF, and as a result, the
      guidelines have been recently revised using an evidence-based approach.
      Meanwhile, several epidemiologic studies have yielded data that identify
      potential risk factors and that better define the societal burden of IPF. This
      article summarizes the approach to diagnosing IPF and reviews epidemiologic data
      on IPF.

PMID- 22365245
TI  - Idiopathic pulmonary fibrosis: phenotypes and comorbidities.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease of the lung
      with an unknown etiology and limited treatment options. Three distinct phenotypes
      of IPF have been proposed: combined pulmonary fibrosis and emphysema,
      disproportionate pulmonary hypertension in IPF, and rapidly progressive IPF.
      Although treatment options for IPF are limited, much can be done to identify and
      alleviate symptoms from comorbidities, potentially improving the overall quality
      of life and well-being of these patients. This article describes emerging
      evidence to support the hypothesis that there is more than one phenotype for IPF
      and describes the common comorbidities seen in this disease.

PMID- 22365246
TI  - Acute exacerbation of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive and ultimately fatal
      disease, the clinical course of which in individual patients is highly variable.
      Sudden deterioration of a patient's respiratory condition during a stable course
      is not uncommon. Many cases of uncertain etiology have been called acute
      exacerbation (AEx) of IPF, under the assumption of sudden acceleration of the
      underlying disease process. In recent years, several studies have reported the
      clinical significance of AEx-IPF. In 2007 Collard and colleagues created a
      Consensus Perspective, which proposed consensus definition and standard
      diagnostic criteria. This review primarily discusses studies performed after this
      Consensus Perspective.

PMID- 22365247
TI  - Idiopathic pulmonary fibrosis: pathobiology of novel approaches to treatment.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown cause
      that conveys a dismal prognosis. In the United States there are currently no
      licensed therapies for treatment of IPF. The development of effective IPF
      clinical trials networks across the United States and Europe, however, has led to
      key developments in the treatment of IPF. Advances in understanding of the
      pathogenetic processes involved in the development of pulmonary fibrosis have led
      to novel therapeutic targets. These developments offer hope that there may, in
      the near future, be therapeutic options available for treatment of this
      devastating disease.

PMID- 22365248
TI  - Management of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a deadly progressive lung disease without
      an effective standard treatment approach. Because of the complexity and
      uncertainties of IPF treatment, therapeutic decisions need to be tailored to the
      individual patient, after discussing the potential benefits and pitfalls.
      Pirfenidone has been approved for the treatment of IPF in many countries, but is
      not recommended as a first-choice therapy by current guidelines because of the
      lack of a definite efficacy. Randomized controlled trials represent a valid
      choice for patients with IPF, and their completion is important in improving both
      survival and quality of life.

PMID- 22365250
TI  - Nonspecific interstitial pneumonia.
AB  - Traditionally, a subset of patients diagnosed as having idiopathic pulmonary
      fibrosis had positive results on cellular biopsies (prominent lymphoplasmacytic
      inflammation), bronchoalveolar lavage lymphocytosis, a clinical response to
      steroids, and a better long-term prognosis. On review of the lung histopathology,
      the lesion was characterized by varying degrees of inflammation and fibrosis.
      This entity is now recognized as a distinct entity among idiopathic interstitial
      pneumonias.

PMID- 22365251
TI  - Interstitial lung disease in the connective tissue diseases.
AB  - The connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders
      in which interstitial lung disease (ILD) is common and clinically important.
      Interstitial lung disease may be the first manifestation of a CTD in a previously
      healthy patient. CTD-associated ILD frequently presents with the gradual onset of
      cough and dyspnea, although rarely may present with fulminant respiratory
      failure. Infection and drug reaction should always be ruled out. A diagnosis of
      idiopathic ILD should never be made without a careful search for subtle evidence
      of underlying CTD. Treatment of CTD-ILD typically includes corticosteroids and
      immunosuppressive agents.

PMID- 22365252
TI  - Chronic hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation
      of environmental antigens. Chronic HP may mimic other fibrotic lung diseases,
      such as idiopathic pulmonary fibrosis. Recognition of the antigen is important
      for diagnosis; avoidance of further exposure is critical for treatment. Fibrosis
      on biopsy or high-resolution computed tomography is a predictor of increased
      mortality. Additional research is needed to understand why the disease develops
      only in a minority of exposed individuals and why cases of chronic HP may
      progress without further antigen exposure.

PMID- 22365249
TI  - Genetic interstitial lung disease.
AB  - The interstitial lung diseases (ILDs), or diffuse parenchymal lung diseases, are
      a heterogeneous collection of more than 100 different pulmonary disorders that
      affect the tissue and spaces surrounding the alveoli. Patients affected by ILD
      usually present with shortness of breath or cough; for many, there is evidence of
      pulmonary restriction, decreased diffusion capacity, and radiographic appearance
      of alveolar and/or reticulonodular infiltrates. This article reviews the
      inherited ILDs, with a focus on the diseases that may be seen by pulmonologists
      caring for adult patients. The authors conclude by briefly discussing the utility
      of genetic testing in this population.

PMID- 22365253
TI  - Smoking-related interstitial lung diseases.
AB  - Cigarette smoke, a toxic collection of thousands of chemicals generated from
      combustion of tobacco, is recognized as the primary causative agent of certain
      diffuse interstitial and bronchiolar lung diseases. Most patients afflicted with
      these disorders are cigarette smokers, and smoking cessation has been shown to be
      capable of inducing disease remission and should occupy a pivotal role in the
      management of all smokers with these diffuse lung diseases. The role of
      pharmacotherapy with corticosteroids or other immunomodulating agents is not well
      established but may be considered in patients with progressive forms of smoking
      related interstitial lung diseases.

PMID- 22365254
TI  - Lung transplantation for interstitial lung disease.
AB  - For selected parenchymal lung disease patients who fail to respond to medical
      therapy and demonstrate declines in function that place them at increased risk
      for mortality, lung transplantation should be considered. Lung transplantation
      remains a complex medical intervention that requires a dedicated recipient and
      medical team. Despite the challenges, lung transplantation affords appropriate
      patients a reasonable chance at increased survival and improved quality of life.
      Lung transplantation remains an appropriate therapeutic option for selected
      patients with parenchymal lung disease.

PMID- 22365255
TI  - Interstitial lung diseases. Preface.

PMID- 22365256
TI  - Cataract surgery in eyes with nanophthalmos and relative anterior microphthalmos.
AB  - PURPOSE: To compare the refractive outcome and postoperative complications of
      cataract surgery among nanophthalmos and relative anterior microphthalmos and the
      normal control eyes. DESIGN: Retrospective case-control series. METHODS:
      Seventeen eyes with nanophthalmos, 29 eyes with relative anterior microphthalmos,
      and 54 normal control eyes were enrolled in this study. The subjects were divided
      into 3 diagnostic subgroups according to the following: nanophthalmos with an
      axial length <20.5 mm and without morphologic malformation; relative anterior
      microphthalmos with a corneal diameter (CD) <= 11 mm, an anterior chamber depth
      (ACD) <= 2.2 mm, and an axial length (AL) >= 20.5 mm; and normal control group
      eyes defined as an AL >= 20.5 mm with a CD >11 mm or an ACD >2.2 mm. The
      implanted intraocular lens (IOL) power was used to calculate the predicted
      postoperative refraction error according to 4 IOL power formulas: SRK II, SRK/T,
      Hoffer Q, and Holladay 1. With each formula, the mean numeric error and mean
      absolute error were calculated. At postoperative 2 months, the endothelial cell
      count and the complications were analyzed. RESULTS: As measured by mean numeric
      error or mean absolute error, there was a significant difference among the 3
      groups based on SRK II, SRK/T, and Hoffer Q, with less predictability in the
      nanophthalmic eyes. In eyes with nanophthalmos, the Holladay 1 produced the best
      refractive results as measured by mean numeric error (P < .001). A higher
      occurrence rate of posterior capsule rupture (11.7%) was shown in the
      nanophthalmic eyes. The difference among the 3 groups for the postoperative
      endothelial cell loss was not significant (P = .421). CONCLUSIONS: The refractive
      predictability and postoperative outcome was poorer in the eyes with
      nanophthalmos compared to the eyes with relative anterior microphthalmos or
      normal control.

PMID- 22365257
TI  - Exploration of a possible association between the tryptophan hydroxylase 2 (TPH2)
      gene and panic symptoms induced by carbon dioxide in healthy individuals.

PMID- 22365258
TI  - Cytokinin dehydrogenase differentially regulates cytokinin and indirectly affects
      hydrogen peroxide accumulation in tomato leaf.
AB  - Cytokinin dehydrogenase (CKX) catalyzes the irreversible degradation of
      cytokinins (CKs). CKs play a role in the regulation of hydrogen peroxide
      (H(2)O(2)) accumulation while H(2)O(2) is involved in chlorophyll degradation.
      Here, we elucidated how CKX differentially regulates representative CK levels and
      indirectly influence H(2)O(2) accumulation in tomato leaves. We induced drought,
      salt and iron-deficiency stresses in tomato plants and found that chlorosis
      inducing stresses (salt and iron-deficiency) induced lower chlorophyll levels as
      compared to drought stress and control. Protein gel blot analysis detected two
      CKXs in tomato leaves: a 35 kDa protein (CKX35) found in chlorotic leaves
      associated with a reduction in representative CK levels and high H(2)O(2)
      concentrations, and a 37 kDa protein (CKX37) found in green leaves associated
      with representative CKs and H(2)O(2) at normal levels. In summary, CKX isoforms
      in the tomato leaf appear to have distinct roles in differentially regulating CK
      levels and indirectly influencing H(2)O(2) accumulation.

PMID- 22365259
TI  - Mechanical tricuspid valve replacement is not superior in patients younger than
      65 years who need long-term anticoagulation.
AB  - BACKGROUND: We evaluated long-term results of tricuspid valve replacement (TVR)
      with mechanical valves and bioprostheses in patients less than 65 years old who
      needed anticoagulation therapy irrespective of TVR. METHODS: Among 156 patients
      who underwent TVR from January 1996 to April 2010, 119 patients younger than 65
      years who needed anticoagulation therapy independent of the TVR were studied.
      Anticoagulation therapy was needed owing to left-sided mechanical valves (n =
      11), atrial fibrillation (n = 13), or both (n = 95). Seventy patients underwent
      mechanical TVR, and 49 underwent bioprosthetic TVR. The follow-up duration was 68
      +/- 38 months. Propensity score-adjusted analyses were performed. RESULTS: Early
      postoperative outcomes were similar between groups, with an operative morality
      rate of 6.7% (8 of 119). Overall survival rates at 5 and 10 years were 86.4% and
      80.3%, respectively. There were no differences in propensity score-adjusted
      overall survival rates between the two groups (p = 0.291). Freedom from the
      composite endpoint of thrombosis, embolism, and bleeding was lower in the
      mechanical TVR group than in the bioprosthetic TVR group (76.3% and 70.0% at 5
      and 10 years, respectively, versus 97.6% and 97.6%, p = 0.020). Five- and 10-year
      valve-related event-free survivals were also lower in the mechanical TVR group
      than in the bioprosthetic TVR group, although not statistically significant
      (75.0% and 61.7% versus 89.2% and 80.3%, p = 0.129). CONCLUSIONS: Even in younger
      patients who need anticoagulation therapy irrespective of TVR, mechanical TVR is
      not superior because of increased occurrence of valve-related events, especially
      the composite of thrombosis, embolism, and bleeding.

PMID- 22365260
TI  - [Assessment of movements of the different anatomic portions of the bladder,
      implications for image-guided radiation therapy for bladder cancer].
AB  - PURPOSE: To assess interfraction and intrafraction bladder wall movements in the
      different anatomic portions of the bladder. PATIENTS AND METHODS: Six patients
      were treated for prostate cancer with conformal irradiation. Daily online cone
      beam computed tomography was performed for repositioning and an additional one
      was performed following irradiation once weekly. Four craniocaudal levels were
      defined to calculate movements amplitudes compared to the scanner tracking: level
      1 at the bladder neck, level 2 at mid-height of the bladder, level 3 at mid
      height of the dome, level 4 at the apex in a distended bladder. Bladder height
      was also measured. RESULTS: On 198 daily cone beam computed tomographies, radial
      bladder right/left/anterior/posterior wall displacements at level 2 were 0.08 +/-
      0.24, 0.11 +/- 0.33, 0.16 +/- 0.45 and 0.14 +/- 0.50 cm and at level 3 0.07 +/-
      0.78, 0.18 +/- 0.98, 0.43 +/- 0.94 and 0.04 +/- 1.02 cm. Dome and neck
      displacements were 0.08 +/- 1.41 cm and 0.08 +/- 0.64 cm. Seventeen cone beam
      computed tomographies were done following irradiation. Radial bladder
      right/left/anterior/halfway up the trine wall displacements at level 2 before and
      after irradiation were 0.02+/-0.18, 0.01+/-0.30, 0.09 +/- 0.32 and 0.22 +/- 0.42
      cm and at level 3 0.27 +/- 0.60, 0.37 +/- 1.15, 0.18 +/- 0.87 and 0.54 +/- 1.68
      cm. CONCLUSION: Significant bladder wall displacements were observed on the
      anterior wall and upper portion of the bladder. Isotropic margins may not be
      sufficient to account for inter- and intrafraction bladder wall displacements at
      the latter levels. Tailored bladder anatomy-based anisotropic margins may be
      necessary to optimally spare the small intestine and to guaranty proper tumour
      coverage in case of bladder cancer. For upper bladder tumours, margins of over 2
      cm would be necessary, which make them less adequate for external beam
      irradiation.

PMID- 22365261
TI  - Gender disparities in dietary status and its risk factors in underserved
      populations.
AB  - OBJECTIVES: To examine dietary status and its risk factors among adults aged 40
      74 years at high risk of colorectal cancer (CRC) in an economically and medically
      underserved population. STUDY DESIGN: Cross-sectional survey in 2007. METHODS: A
      survey was conducted among a random sample (n = 1844) nested in a screening
      cohort of a rural population in Jiashan County, China. Information about diet,
      family history of CRC and other factors was collected by questionnaire. The
      primary outcome was dietary status, assessed by consumption (servings/week) of
      plant-based food and unhealthy food. Linear or multinomial logistic regressions
      were used to determine risk factors for dietary status. RESULTS: On average,
      individuals with a family history of CRC ate 2.25 fewer servings of plant-based
      food each week compared with individuals without a family history of CRC.
      Individuals who smoked and drank alcohol ate less plant-based food. After
      stratification by gender, there were multiple determinants for consumption of
      plant-based food for men, including family history of CRC, smoking, alcohol
      consumption and income. For women, the only association was found for income.
      Consumption of unhealthy food was positively associated with high income and high
      body mass index. Determinants for an unhealthy diet were the same in both
      genders. CONCLUSIONS: There are gender disparities in the consumption of plant
      based food and the risk factors for CRC in medically and economically underserved
      populations. Men's insufficient consumption of plant-based food and unhealthy
      lifestyle behaviours, such as smoking and drinking, may explain, in part, why men
      have a higher risk of CRC than women.

PMID- 22365262
TI  - Coronary artery bypass operations for elderly patients in California, 2003 to
      2008.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is no longer rare for elderly
      patients. This study evaluates operative mortality and the effects of off-pump
      CABG (OPCAB) on mortality for elderly Californians between 2003 and 2008.
      METHODS: All isolated CABGs in California for 2003 to 2008 were classified into
      cohorts by age: (1) younger than 75, (2) 75 to 84, and (3) 85 or older.
      Multivariable logistic regression models were developed for operative mortality.
      Trend analyses for observed and predicted mortality, and observed-to-expected
      mortality ratios were performed. The "recycled predictions" method was used to
      assess the effect of OPCAB on operative mortality. RESULTS: Among 101,710
      isolated CABGs between 2003 and 2008, 22.0% were in cohort 2 and 2.3% were in
      cohort 3. Predicted mortality was unchanged for cohorts 2 and 3 (all p > 0.05),
      but observed-to-expected mortality ratios declined from 0.958 to 0.633 for cohort
      2 (p = 0.021) and from 1.027 to 0.965 for cohort 3 (p = 0.168). The proportion of
      OPCAB for patients aged 75 years or older increased from 25.0% to 29.1% between
      2003 and 2008. The adjusted odds ratio for operative mortality for OPCAB in
      patients aged 75 years or older was 0.752 (95% confidence interval, 0.650 to
      0.871; p < 0.001) compared with on-pump CABG for the same age cohort.
      CONCLUSIONS: In California, overall predicted mortality was unchanged for elderly
      patients between 2003 and 2008, but operative mortality significantly decreased
      for patients aged 75 to 84. Improvement for CABG patients aged 85 years or older
      was insignificant. The increase in the number of OPCAB patients was associated
      with decreased mortality for elderly patients.

PMID- 22365263
TI  - Morbidity of the arterial switch operation.
AB  - BACKGROUND: The arterial switch operation (ASO) has become a safe, reproducible
      surgical procedure with low mortality in experienced centers. We examined
      morbidity, which remains significant, particularly for complex ASO. METHODS: From
      2003 to 2011, 101 consecutive patients underwent ASO, arbitrarily classified as
      "simple" (n=52) or "complex" (n=49). Morbidity was measured in selected
      complications and postoperative hospitalization. Three outcomes were analyzed:
      ventilation time, postextubation hospital length of stay, and a composite
      morbidity index, defined as ventilation time+postextubation hospital length of
      stay+occurrence of selected major complications. Complexity was measured with the
      comprehensive Aristotle score. RESULTS: The operative mortality was zero. Twenty
      five major complications occurred in 23 patients: 6 of 25 (12%) in simple ASO and
      19 of 49 (39%) in complex ASO (p=0.002). The most frequent complication was
      unplanned reoperation (15 vs 6, p=0.03). No patients required permanent pacing.
      The complex group had a significantly higher morbidity index and longer
      ventilation time and postextubation hospital length of stay. In multivariate
      analysis, factors independently predicting higher morbidity were the
      comprehensive Aristotle score, arch repair, bypass time, and malaligned
      commissures. Myocardial infarction caused one sudden late death at 3 months. Late
      coronary failure was 2%. Overall survival was 99% at a mean follow-up of 49+/-27
      months. CONCLUSIONS: In this consecutive series without operative mortality,
      morbidity was significantly higher in complex ASO. The only anatomic incremental
      risk factors for morbidity were aortic arch repair and malaligned commissures,
      but not primary diagnosis, weight less than 2.5 kg, or coronary patterns.

PMID- 22365264
TI  - Composition and production rate of pharmaceutical and chemical waste from Xanthi
      General Hospital in Greece.
AB  - The objective of this work was to determine the composition and production rates
      of pharmaceutical and chemical waste produced by Xanthi General Hospital in
      Greece (XGH). This information is important to design and cost management systems
      for pharmaceutical and chemical waste, for safety and health considerations and
      for assessing environmental impact. A total of 233 kg pharmaceutical and 110 kg
      chemical waste was collected, manually separated and weighed over a period of
      five working weeks. The total production of pharmaceutical waste comprised 3.9%
      w/w of the total hazardous medical waste produced by the hospital. Total
      pharmaceutical waste was classified in three categories, vial waste comprising
      51.1%, syringe waste with 11.4% and intravenous therapy (IV) waste with 37.5% w/w
      of the total. Vial pharmaceutical waste only was further classified in six major
      categories: antibiotics, digestive system drugs, analgesics, hormones,
      circulatory system drugs and "other". Production data below are presented as
      average (standard deviation in parenthesis). The unit production rates for total
      pharmaceutical waste for the hospital were 12.4 (3.90) g/patient/d and 24.6
      (7.48) g/bed/d. The respective unit production rates were: (1) for vial waste 6.4
      (1.6) g/patient/d and 13 (2.6) g/bed/d, (2) for syringe waste 1.4 (0.4)
      g/patient/d and 2.8 (0.8) g/bed/d and (3) for IV waste 4.6 (3.0) g/patient/d and
      9.2 (5.9) g/bed/d. Total chemical waste was classified in four categories,
      chemical reagents comprising 18.2%, solvents with 52.3%, dyes and tracers with
      18.2% and solid waste with 11.4% w/w of the total. The total production of
      chemical waste comprised 1.8% w/w of the total hazardous medical waste produced
      by the hospital. Thus, the sum of pharmaceutical and chemical waste was 5.7% w/w
      of the total hazardous medical waste produced by the hospital. The unit
      production rates for total chemical waste for the hospital were 5.8 (2.2)
      g/patient/d and 1.1 (0.4) g/exam/d. The respective unit production rates were:
      (1) for reagents 1.7 (2.4) g/patient/d and 0.3 (0.4) g/examination/d, (2) for
      solvents 248 (127) g/patient/d and 192 (101) g/examination/d, (3) for dyes and
      tracers 4.7 (1.4) g/patient/d and 2.5 (0.9) g/examination/d and (4) for solid
      waste 54 (28) g/patient/d and 42 (22) g/examination/d.

PMID- 22365265
TI  - Open capsular shift and arthroscopic capsular plication for treatment of
      multidirectional instability.
AB  - PURPOSE: To compare the results of open inferior capsular shift with arthroscopic
      capsular plication for multidirectional instability in patients without a Bankart
      lesion. We hypothesized that there is no difference with regard to the specific
      clinical outcomes evaluated, including recurrent instability, range of motion,
      return to sport, and complications. METHODS: We conducted a comprehensive
      literature search. Databases searched included PubMed from 1966 to 2010, the
      Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL (Cumulative
      Index to Nursing and Allied Health Literature) from 1982 to 2010, and SPORTDiscus
      from 1975 to 2010. Limits included English language, human subjects, and title.
      RESULTS: We found 7 articles with a total of 197 patients (219 shoulders) that
      met our inclusion criteria. The data did not clearly show open treatment to be
      superior to arthroscopic treatment. No study reported a consistent loss of
      greater than 40 degrees  of external rotation. No technique showed significantly
      less external rotation loss over the other. Whereas there was a slight trend
      toward increased return to sport for patients treated arthroscopically, no clear
      conclusion can be drawn given the variability of reporting in the reviewed
      studies. Analysis of complications shows that both procedures are reliably safe
      with minimal complications. CONCLUSIONS: When one is evaluating patients with
      traumatic or atraumatic onset of shoulder instability in 2 directions and no
      structural lesions, arthroscopic capsular plication yields comparable results to
      open capsular shift with regard to recurrent instability, return to sport, loss
      of external rotation, and overall complications.

PMID- 22365266
TI  - Incidence of bilateral discoid lateral meniscus in an Asian population: an
      arthroscopic assessment of contralateral knees.
AB  - PURPOSE: To investigate the incidence of bilateral discoid lateral meniscus (DLM)
      and to evaluate the arthroscopic features of lateral meniscus in asymptomatic
      contralateral knees in an Asian population who presented with symptomatic DLMs.
      METHODS: This study prospectively enrolled 52 consecutive patients who underwent
      arthroscopic procedures for symptomatic DLMs (31 complete and 21 incomplete) and
      who consented to the examination of the contralateral knee at the time of
      arthroscopy. Types of DLMs and of meniscus tears were assessed by use of
      arthroscopic findings. Preoperative and postoperative functional outcomes were
      evaluated with Lysholm and Tegner activity scores. RESULTS: Arthroscopic
      examinations showed 21 complete DLMs, 19 incomplete DLMs, 11 normal lateral
      menisci, and 1 ring-shaped lateral meniscus in contralateral knees. The incidence
      of bilateral DLM in our study population was 79% (41 of 52 contralateral knees).
      Furthermore, 65% of patients (34 pairs of knees) had the same DLM types. In
      addition, 3 pairs of knees with complete DLMs had menisci of different
      thicknesses. DLM tears were observed in 2 contralateral knees (1 radial and 1
      longitudinal) and were treated by partial central meniscectomy. CONCLUSIONS: This
      study provides evidence of the high prevalence of bilateral DLM in an Asian
      population.

PMID- 22365267
TI  - Long-term outcome of arthroscopic massive rotator cuff repair: the importance of
      double-row fixation.
AB  - PURPOSE: The purpose of this study was to (1) evaluate the long-term functional
      outcome of arthroscopic rotator cuff repair of massive rotator cuff tears (RCTs)
      and (2) compare double-row (DR) and single-row (SR) repairs. METHODS: This was a
      retrospective review of massive RCTs treated with an arthroscopic rotator cuff
      repair over an 8-year period. Minimum 5-year follow-up was available for 126
      repairs at a mean of 99 months. Among 107 complete repairs, there were 62 SR and
      45 DR repairs. Functional outcome was determined by University of California, Los
      Angeles (UCLA) and American Shoulder and Elbow Surgeons scores. A multivariate
      analysis was performed to examine the role of a DR repair. RESULTS: For all
      repairs combined, improvements were observed in forward flexion (132 degrees  v
      168 degrees ), pain (6.3 v 1.3), UCLA score (15.7 v 30.7), and American Shoulder
      and Elbow Surgeons score (41.7 v 85.7) (P < .001). A good or excellent outcome,
      obtained in 78% of cases, was associated with a complete repair (P = .035) and a
      DR repair (P = .008). When we excluded partial repairs, postoperative UCLA gain
      was greater after a DR repair (P = .007). Patients reported their shoulder as
      feeling closer to normal after a DR repair compared with an SR repair (93.5% v
      84.4%, P = .006). A DR repair was 4.9 times more likely to lead to a good or
      excellent outcome (P = .021). CONCLUSIONS: When a DR repair of a massive RCT is
      possible, on the basis of the ability to mobilize the tendons, a better long-term
      functional outcome can be expected compared with an SR repair. Given the known
      high risk of recurrence after repair of massive RCTs and the knowledge that
      functional outcome is related to recurrence, a DR repair of massive RCTs should
      be performed when there is sufficient tendon mobility.

PMID- 22365268
TI  - Diagnostics of femoroacetabular impingement and labral pathology of the hip: a
      systematic review of the accuracy and validity of physical tests.
AB  - PURPOSE: Femoroacetabular impingement (FAI) and labral pathology have been
      recognized as causative factors for hip pain. The clinical diagnosis is now based
      on MRI-A (magnetic resonance imaging-arthrogram) because the physical diagnostic
      tests available are diverse and information on diagnostic accuracy and validity
      is lacking. The purpose of this systematic review was to identify the diagnostic
      accuracy and validity of physical tests that are used to assess FAI and labral
      pathology of the hip joint. METHODS: We performed a computerized literature
      search using PubMed, Medline, Web of Science, PEDro, the Cochrane Library, and
      CINAHL (Cumulative Index to Nursing and Allied Health Literature) (through
      EBSCO). Studies describing tests and diagnostic accuracy studies were included.
      All included studies were assessed by the Levels of Evidence for Primary Research
      Questions list. All diagnostic accuracy studies were assessed by the QUADAS
      (Quality Assessment of Diagnostic Accuracy Studies) score. RESULTS: We included
      21 studies in which 18 different tests were described. For 11 of these tests,
      diagnostic accuracy figures were presented. Sensitivity was examined for all
      tests. Other diagnostic accuracy figures were often lacking, and when available,
      these were low. All articles describing tests had Level IV or V evidence. All
      diagnostic accuracy studies, except 1, had Level II or III evidence. Three
      articles had a good QUADAS score. CONCLUSIONS: In previous studies a wide range
      of physical diagnostic tests have been described. Little is known about the
      diagnostic accuracy and validity of these tests, and if available, these figures
      were low. The quality of the studies investigating these tests is too low to
      provide a conclusive recommendation for the clinician. Thus, currently, no
      physical tests are available that can reliably confirm or discard the diagnoses
      of FAI and/or labral pathology of the hip in clinical practice. LEVEL OF
      EVIDENCE: Level III, systematic review of Level III studies.

PMID- 22365269
TI  - Characterization of presbyequilibrium among institutionalized elderly persons.
AB  - OBJECTIVE: The aim was to characterize dizziness, vertigo, poor maintenance of
      posture, and sudden instabilities (called presbyequilibrium) among
      institutionalized elderly to model and identify possible treatable causes.
      METHODS: A questionnaire based study focusing on symptoms among 72 elderly
      persons from a single residential facility and followed them for 3 years.
      RESULTS: Dizziness, vertigo, poor maintenance of posture, and black-outs were
      reported by 68% of the 72 elderly and make them at risk for falls, and reduced
      quality of life. The most common complaint was postural instability, with a
      tendency to fall. "Spinning" vertigo and "floating" sensation had a strong inter
      correlation and correlated with habitual falls. The various dizziness symptoms
      often occurred in combinations. Attacks of self-experienced syncope never
      occurred alone but always in combination with "spinning vertigo" or "tendency to
      fall". In factorial analysis, presbyequilibrium could be divided into six
      categories. Two of these categories correlated with falls. CONCLUSIONS: Among
      elderly, presbyequilibrium is commonly characterized by a combination of
      phenomena involving perceptual, orientation, postural, and autonomic
      manifestations. It is often difficult to obtain an accurate history from the
      elderly and the presence of vestibular symptoms is frequently overlooked. Taking
      a careful history and utilizing the classification of symptoms that emerged from
      the factorial analysis may give a deeper understanding of the etiology of
      presbyequilibrium, thereby facilitating appropriate rehabilitation.

PMID- 22365270
TI  - [Congenital cytomegalovirus infection and cortical/subcortical malformations].
AB  - INTRODUCTION: Intrauterine infection due to cytomegalovirus is the most common of
      the intrauterine viral/parasitic infections that affect the central nervous
      system and cause permanent lesions in the cortex as well as the subcortical white
      matter. Studies using brain magnetic resonance imaging (MRI) are limited.
      MATERIAL AND METHODS: Six patients (4 females and 2 males) were studied in the
      first months of life in order to make a diagnosis of congenital cytomegalovirus,
      and identify the cortical and subcortical lesions using the necessary MRI
      sequences. RESULTS: The six patients showed malformations of cortical development
      (MDC) (schizencephaly, polymicrogyria or lissencephaly-pachygyria) from the
      neonatal period, and diffuse changes of the white matter, which remained with few
      changes during the first two years. They then began reducing in size in the form
      of high signal areas in T2, restricted to certain areas, and were evident for a
      few years more with little change. CONCLUSION: Intrauterine infection due to
      cytomegalovirus causes changes in the cortical grey matter, which consists of
      MDC, and in the subcortical white matter. The latter show a changing aspect as
      they appear as diffuse and wide areas of high signal intensity, which is usually
      due to delay in myelinisation, but could also be caused directly by the
      cytomegalovirus. These changes in the white matter are subjected to morphological
      changes throughout the first years of life, leading to brain atrophy. The
      neurological sequelae of these lesions left by these alterations are severe and
      chronic.

PMID- 22365271
TI  - Proteomic study of proteolysis during ripening of Cheddar cheese made from milk
      over a lactation cycle.
AB  - Milk for cheese production in Ireland is predominantly produced by pasture-fed
      spring-calving herds. Consequently, there are marked seasonal changes in milk
      composition, which arise from the interactive lactational, dietary and
      environmental factors. In this study, Cheddar cheese was manufactured on a
      laboratory scale from milk taken from a spring calving herd, over a 9-month
      lactation cycle between early April and early December. Plasmin activity of 6
      months-old Cheddar cheese samples generally decreased over ripening time. One
      dimensional urea-polyacrylamide gel electrophoresis (PAGE) of cheese samples
      taken after 6 months of ripening showed an extensive hydrolysis of caseins, with
      the fastest hydrolysis of alpha(s1)-caseins in cheeses made in August. A
      proteomic comparison between cheeses produced from milk taken in April, August
      and December showed a reduction in levels of beta-casein and appearance of
      additional products, corresponding to low molecular weight hydrolysis products of
      the caseins. This study has demonstrated that a seasonal milk supply causes
      compositional differences in Cheddar cheese, and that proteomic tools are helpful
      in understanding the impact of those differences.

PMID- 22365272
TI  - Cognitive control components and speech symptoms in people with schizophrenia.
AB  - Previous schizophrenia research suggests poor cognitive control is associated
      with schizophrenia speech symptoms. However, cognitive control is a broad
      construct. Two important cognitive control components are poor goal maintenance
      and poor verbal working memory storage. In the current research, people with
      schizophrenia (n=45) performed three cognitive tasks that varied in their goal
      maintenance and verbal working memory storage demands. Speech symptoms were
      assessed using clinical rating scales, ratings of disorganized speech from typed
      transcripts, and self-reported disorganization. Overall, alogia was associated
      with both goal maintenance and verbal working memory tasks. Objectively rated
      disorganized speech was associated with poor goal maintenance and with a task
      that included both goal maintenance and verbal working memory storage demands. In
      contrast, self-reported disorganization was unrelated to either amount of
      objectively rated disorganized speech or to cognitive control task performance,
      instead being associated with negative mood symptoms. Overall, our results
      suggest that alogia is associated with both poor goal maintenance and poor verbal
      working memory storage and that disorganized speech is associated with poor goal
      maintenance. In addition, patients' own assessment of their disorganization is
      related to negative mood, but perhaps not to objective disorganized speech or to
      cognitive control task performance.

PMID- 22365273
TI  - Atypical presentations of 22q11.2 deletion syndrome: explaining the genetic
      defects and genome architecture.
AB  - 22q11.2 deletion syndrome, the most common microdeletion syndrome, exhibits a
      broad range of phenotypes, implying a cumbersome diagnosis due to atypical or
      paucisymptomatic presentations. We present two atypical cases of 22q11.2 deletion
      syndrome and suggest a preferential occurrence of the breakpoints in regions poor
      in repetitive elements of SINE/Alu family.

PMID- 22365274
TI  - The influence of personality and dysfunctional sleep-related cognitions on the
      severity of insomnia.
AB  - Previous findings suggest that personality traits and dysfunctional sleep-related
      cognitions may perpetuate insomnia, but findings concerning this have been
      scarce. Thus, we hypothesized that personality and sleep-related cognitions
      influence the severity of insomnia, and investigated the association personality
      and sleep-related cognitions had with various sleep-related parameters, including
      severity of insomnia. Forty-four patients with psychophysiological insomnia were
      assessed using The Temperament and Character Inventory, the Insomnia Severity
      Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the
      Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal
      Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was
      significantly and positively correlated with harm avoidance, self-transcendence
      and sleep-related cognitions, and negatively correlated with novelty seeking,
      reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions
      were positively correlated with insomnia severity and sleep quality. Stepwise
      multiple regression analysis showed that sleep-related cognitions, depression and
      reward dependence scores were significant determinants of insomnia severity, and
      that sleep-related cognitions and self-transcendence were significant positive
      determinants of sleep quality. Reward dependence, depression and sleep-related
      cognitions were associated with insomnia severity, and comparison with previous
      findings implied that 'internalizing behavior' and depression may be more
      plausible candidates for the link between personality and insomnia than anxiety.
      Considering the major role of cognitive-behavioral treatment (CBT) in the
      treatment of insomnia, assessment of these factors and management of sleep
      related cognitions may help alleviate symptoms in patients with insomnia.

PMID- 22365275
TI  - The Beck Depression Inventory and General Health Questionnaire as measures of
      depression in the general population: a validation study using the Composite
      International Diagnostic Interview as the gold standard.
AB  - The Beck Depression Inventory (BDI) and the General Health Questionnaire (GHQ)
      are commonly used in population studies as measures of depression. We examined in
      a population sample the validity of four scales for depressive symptoms, the GHQ
      12, the 21- and 13-item versions of the BDI, and a new 6-item version of the BDI
      developed for this study. A total of 5561 participants in the "Health 2000"
      survey (30-79 years) completed the four scales and were assessed with the
      Composite International Diagnostic Interview (CIDI), which was used as the
      validation criterion. We selected items for the BDI-6 through an exploratory
      factor analysis for the BDI-21. The accuracy of the scales, including the BDI-6,
      was satisfactory (c-statistics 0.88-0.92 for depression within the past 2 weeks
      and 0.80-0.83 within the past 12 months) and slightly better for men (0.92-0.96
      and 0.85-0.87) than for women (0.86-0.88 and 0.78-0.79). Higher scores in all the
      scales were associated with more severe depression and more recent depressive
      episodes. This study suggests that various versions of the BDI and the GHQ-12 are
      useful in detecting depressive disorders in the general population. Even the 6
      item version of the BDI showed acceptable criterion validity, although
      replication in an independent dataset is needed to confirm its validity.

PMID- 22365276
TI  - Eichhornia crassipes capability to remove naphthalene from wastewater in the
      absence of bacteria.
AB  - The aim of the current study was to investigate the potential of an aquatic
      plant, the water hyacinth (Eichhornia crassipes) devoid rhizospheric bacteria, to
      reduce naphthalene (a polyaromatic hydrocarbon) present in wastewater and
      wetlands. The capability of sterile water hyacinth plants to remove naphthalene
      from water and wastewater was studied in batch systems. Water hyacinths enhance
      the removal of pollutants through their consumption as nutrients and also through
      microbial activity of their rhizospheric bacteria. Experimental kinetics of
      naphthalene removal by water hyacinth coupled with natural rhizospheric bacteria
      was 100% after 9 d. Plants, decoupled of rhizospheric bacteria, reduced
      naphthalene concentration up to 45% during 7 d. Additionally, naphthalene uptake
      by water hyacinth revealed a biphasic behavior: a rapid first phase completed
      after 2.5 h, and a second, considerably slower rate, phase (2.5-225 h). In
      conclusion, water hyacinth devoid rhizospheric bacteria reduced significantly
      naphthalene concentration in water, revealing a considerable plant contribution
      in the biodegradation process of this pollutant.

PMID- 22365277
TI  - Electrochemical incineration of sulfanilic acid at a boron-doped diamond anode.
AB  - The anodic oxidation of sulfanilic acid solutions has been studied in acidic
      medium using a divided cell with a boron-doped diamond (BDD) anode and a
      stainless steel cathode. Overall mineralization was achieved under all
      experimental conditions tested due to the efficient destruction of sulfanilic
      acid and all its by-products with hydroxyl radicals generated at the BDD anode
      from water oxidation. The alternative use of an undivided cell with the same
      electrodes gave rise to the coating of the cathode with polymeric compounds, thus
      preventing the complete electrochemical incineration of sulfanilic acid. The
      solutions treated in the anodic compartment of the divided cell were degraded at
      similar rate under pH regulation within the pH interval 2.0-6.0. The
      mineralization current efficiency was enhanced when the applied current decreased
      and the initial substrate concentration increased. The decay of sulfanilic acid
      was followed by reversed-phase HPLC, showing a pseudo first-order kinetics.
      Hydroquinone and p-benzoquinone were identified as aromatic intermediates by gas
      chromatography-mass spectrometry and/or reversed-phase HPLC. Maleic, acetic,
      formic, oxalic and oxamic acids were detected as generated carboxylic acids by
      ion-exclusion HPLC. Ionic chromatographic analysis of electrolyzed solutions
      revealed that the N content of sulfanilic acid was mainly released as NH(4)(+)
      ion and in much smaller proportion as NO(3)(-) ion.

PMID- 22365278
TI  - Assessment of the environmental fate and effects of azilsartan, a selective
      antagonist of angiotensin II type 1.
AB  - In this paper the results of a thorough evaluation of the environmental fate and
      effects of azilsartan are presented. Azilsartan medoxomil is administered as a
      pro-drug for the treatment of patients with essential hypertension. The pro-drug
      is converted by hydrolysis to the active pharmaceutical ingredient azilsartan.
      Laboratory tests to evaluate the environmental fate and effects of azilsartan
      medoxomil were conducted with azilsartan and performed in accordance with OECD
      test guidelines. The predicted environmental concentration (PEC) in surface water
      was estimated at 0.32 MUg L(-1) (above the action limit of 0.01 MUg L(-1)),
      triggering a Phase II assessment. Azilsartan is not readily biodegradable.
      Results of the water sediment study demonstrated significant shifting of
      azilsartan metabolites to sediment. Based on the equilibrium partitioning method,
      metabolites are unlikely to pose a risk to sediment-dwelling organisms. Ratios of
      the predicted environmental concentrations (PECs) to the predicted-no-effect
      concentrations (PNECs) did not exceed the relevant triggers, and the risk to
      aquatic, sewage treatment plant (STP), groundwater and sediment compartments was
      concluded acceptable. A terrestrial assessment was not triggered. Azilsartan
      poses an acceptable risk to the environment.

PMID- 22365280
TI  - Functions of microRNAs in plant stress responses.
AB  - The discovery of microRNAs (miRNAs) as gene regulators has led to a paradigm
      shift in the understanding of post-transcriptional gene regulation in plants and
      animals. miRNAs have emerged as master regulators of plant growth and
      development. Evidence suggesting that miRNAs play a role in plant stress
      responses arises from the discovery that miR398 targets genes with known roles in
      stress tolerance. In addition, the expression profiles of most miRNAs that are
      implicated in plant growth and development are significantly altered during
      stress. These later findings imply that attenuated plant growth and development
      under stress may be under the control of stress-responsive miRNAs. Here we review
      recent progress in the understanding of miRNA-mediated plant stress tolerance.

PMID- 22365279
TI  - Enchytraeus crypticus as model species in soil ecotoxicology.
AB  - Enchytraeids are ecologically relevant soil organisms, due to their activity in
      decomposition and bioturbation in many soil types worldwide. The enchytraeid
      reproduction test (ERT) guidelines ISO 16387 and OECD 220 are exclusive to the
      genus Enchytraeus and recommend using the species E. albidus with a 6-week test
      period. The suggested alternative, E. crypticus has a shorter generation time
      which may enable the ERT to be twice as fast. To confirm the suitability of a 3
      week test period for E. crypticus, the toxicity of five chemicals, with distinct
      properties and modes of action, was assessed in LUFA 2.2 soil. In all controls
      the validity criteria were met, as survival of E. crypticus was above 92% and
      more than 772 juveniles were produced. The good performance supports its
      appropriateness as model species. Reproduction was more sensitive than survival,
      with only cadmium and 3,5-dichloroaniline causing significant lethal effects in
      the tested concentration ranges. The effect concentration causing 50% reduction
      in the number of juveniles (EC50) was 35 mg kg(-1) for cadmium, <1.0 mg kg(-1)
      for carbendazim, 145 mg kg(-1) for phenanthrene, 275 mg kg(-1) for
      pentachloroaniline and 102 mg kg(-1) for 3,5-dichloroaniline. To evaluate the
      sensitivity of E. crypticus, the present results were compared to literature data
      for E. albidus. In conclusion, E. crypticus is a suitable model species in soil
      ecotoxicology, with advantages such as good control performance and speed,
      leading to a reliable and faster ERT.

PMID- 22365281
TI  - Instrumentation and techniques for examination of the ear, nose, throat, and
      sinus.
AB  - Optimal and accurate management of any patient depends on a detailed history and
      thorough physical examination. The information garnered dictates the definitive
      management of the patient. Adequate examination of the head and neck,
      particularly the upper aerodigestive tract, presents a unique challenge because
      much of the area to be examined is not easily accessible to direct visualization.
      However, advances in medical technology have prompted the evolution of the
      instrumentation and the techniques used to examine this anatomic region. This
      evolution allows for a more informative assessment of the patient and a more
      comfortable experience.

PMID- 22365282
TI  - Re: Thomas Hambrock, Caroline Hoeks, Christina Hulsbergen-van de Kaa, et al.
      Prospective assessment of prostate cancer aggressiveness using 3-T diffusion
      weighted magnetic resonance imaging-guided biopsies versus a systematic 10-core
      transrectal ultrasound prostate biopsy cohort. Eur Urol 2012;61:177-84.

PMID- 22365283
TI  - One-year atherothrombotic vascular events rates in outpatients with recent non
      cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction
      after STroke) registry.
AB  - BACKGROUND: Patients with recent ischemic stroke may have higher risk of
      atherothrombosis than stable patients with established vascular events. Our aims
      were to investigate 1-year atherothrombotic vascular event rates and to assess
      the risk factors for recurrent ischemic stroke in this population. METHODS: This
      prospective cohort study was conducted between January 2007 and July 2009 at 313
      hospitals in Japan. Outpatients who were at least 45 years of age and who had
      received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from
      the last onset of noncardioembolic ischemic stroke. At 12 +/- 3 months after
      enrollment, data on presence/absence of atherothrombotic vascular events were
      collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic
      stroke. RESULTS: A total of 3452 patients were enrolled, and 3411 patients who
      had baseline data were included in the analysis. The 1-year event rate was 3.81%
      (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and
      0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual
      rate of recurrent ischemic stroke was significantly higher in patients who had
      ischemic stroke at least twice than in patients who had first-ever ischemic
      stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis,
      recurrent ischemic stroke was significantly associated with age (P = .0033), the
      presence of diabetes (P = .0129), and waist circumference >=80 cm (P = .0056).
      CONCLUSIONS: Patients with recent ischemic stroke have a higher risk of stroke
      recurrence than stable patients enrolled in the REduction of Atherothrombosis for
      Continued Health (REACH) registry even though they received antiplatelet therapy.
      The rigorous management of risk factors is needed.

PMID- 22365284
TI  - Cerebellar infarction originating from vertebral artery stenosis caused by a
      hypertrophied uncovertebral joint.
AB  - We report a case of cerebellar infarction originating from vertebral artery
      stenosis caused by a hypertrophied uncovertebral joint. A 38-year-old man
      presented with sudden onset of headache, dizziness, and dysarthria. The magnetic
      resonance imaging scan of the brain revealed acute infarction in the right
      cerebellar hemisphere in the territory of the posterior inferior cerebellar
      artery (PICA) and superior cerebellar artery (SCA). Magnetic resonance, 3
      dimensional computed tomographic, and conventional angiography revealed severe
      right vertebral artery stenosis by extrinsic compression of the hypertrophied
      right C5-C6 uncovertebral joint. The diagnosis was acute cerebellar infarction,
      which was probably caused by embolism from the right vertebral artery stenosis
      that was caused by the hypertrophied C5-C6 uncovertebral joint. C5-C6 anterior
      discectomy and fusion were performed together with direct uncovertebral joint
      decompression. Postoperative 3-dimensional computed tomographic angiography
      revealed improvement in antegrade filling in the right vertebral artery. The
      imaging findings for this patient and the pathogenesis of cerebellar infarction
      for our patient are discussed.

PMID- 22365285
TI  - Median levels of serum biomarkers of fetal Down syndrome detected during the
      first trimester among pregnant Thai women.
AB  - OBJECTIVE: To develop Thai-specific medians of serum pregnancy-associated plasma
      protein A (PAPP-A) and free beta-human chorionic gonadotropin (hCG) levels during
      the first trimester of pregnancy and to compare these values to a Caucasian
      specific model for the detection of fetal Down syndrome. METHODS: Serum
      concentrations of PAPP-A and free beta-hCG were measured during the first
      trimester in a group of 2339 Thai women undergoing normal singleton pregnancies.
      RESULTS: Thai reference ranges of PAPP-A and free beta-hCG were established by
      gestational age (70-98 days). The equation of best fit for PAPP-A was: predicted
      median PAPP-A level=28.767 - 0.781*(gestational age in days)+0.006*(gestational
      age in days)(2); r=0.986. The equation of best fit for free beta-hCG was:
      predicted median free beta-hCG level=465.332*10((-0.024*gestational age in
      days)); r=0.881. Weight-corrected models were also derived for each biomarker.
      The Thai-specific reference ranges gave higher positive screening rates than the
      Caucasian-specific model, even after weight correction (5.1% versus 4.0%). The
      Thai-specific models were validated in an independent group of 302 pregnant
      women. CONCLUSION: Ethnic group-specific medians for PAPP-A and free beta-hCG
      should be incorporated during first-trimester screening for fetal Down syndrome.

PMID- 22365287
TI  - Simulation of nuclear quadrupole resonance for sensor probe optimization.
AB  - A simulation method to estimate the detection efficiency of nuclear quadrupole
      resonance (NQR) was proposed for optimizing a sensing probe operating at radio
      frequencies (RFs). It first calculates the transmitted magnetic field from the
      probe coil to the target sample. The nuclei make quadrupole resonance by it. We
      considered this nonlinear reaction to estimate NQR emission by the nuclei. Then
      the received NQR signal intensity from the sample at the probe coil. We
      calculated the efficiency by testing two different probe types (solenoid and
      gradiometer) and by changing the relative positions of the probe and sample. The
      simulation results were in good agreement with the experimental results.

PMID- 22365286
TI  - Y chromosome gene expression in the blood of male patients with ischemic stroke
      compared with male controls.
AB  - BACKGROUND: Sex is suggested to be an important determinant of ischemic stroke
      risk factors, etiology, and outcome. However, the basis for this remains unclear.
      The Y chromosome is unique in males. Genes expressed in males on the Y chromosome
      that are associated with stroke may be important genetic contributors to the
      unique features of males with ischemic stroke, which would be helpful for
      explaining sex differences observed between men and women. OBJECTIVE: We compared
      Y chromosome gene expression in males with ischemic stroke and male controls.
      METHODS: Blood samples were obtained from 40 male patients <=3, 5, and 24 hours
      after ischemic stroke and from 41 male controls (July 2003-April 2007). RNA was
      isolated from blood and was processed using Affymetrix Human U133 Plus 2.0
      expression arrays (Affymetrix Inc., Santa Clara, California). Y chromosome genes
      differentially expressed between male patients with stroke and male control
      subjects were identified using an ANCOVA adjusted for age and batch. A P < 0.05
      and a fold change >1.2 were considered significant. RESULTS: Seven genes on the Y
      chromosome were differentially expressed in males with ischemic stroke compared
      with controls. Five of these genes (VAMP7, CSF2RA, SPRY3, DHRSX, and PLCXD1) are
      located on pseudoautosomal regions of the human Y chromosome. The other 2 genes
      (EIF1AY and DDX3Y) are located on the nonrecombining region of the human Y
      chromosome. The identified genes were associated with immunology, RNA metabolism,
      vesicle fusion, and angiogenesis. CONCLUSIONS: Specific genes on the Y chromosome
      are differentially expressed in blood after ischemic stroke. These genes provide
      insight into potential molecular contributors to sex differences in ischemic
      stroke.

PMID- 22365288
TI  - Time domain para hydrogen induced polarization.
AB  - Para hydrogen induced polarization (PHIP) is a powerful hyperpolarization
      technique, which increases the NMR sensitivity by several orders of magnitude.
      However the hyperpolarized signal is created as an anti-phase signal, which
      necessitates high magnetic field homogeneity and spectral resolution in the
      conventional PHIP schemes. This hampers the application of PHIP enhancement in
      many fields, as for example in food science, materials science or MRI, where low
      B(0)-fields or low B(0)-homogeneity do decrease spectral resolution, leading to
      potential extinction if in-phase and anti-phase hyperpolarization signals cannot
      be resolved. Herein, we demonstrate that the echo sequence (45 degrees -tau-180
      degrees -tau) enables the acquisition of low resolution PHIP enhanced liquid
      state NMR signals of phenylpropiolic acid derivatives and phenylacetylene at a
      low cost low-resolution 0.54 T spectrometer. As low field TD-spectrometers are
      commonly used in industry or biomedicine for the relaxometry of oil-water
      mixtures, food, nano-particles, or other systems, we compare two variants of para
      hydrogen induced polarization with data-evaluation in the time domain (TD-PHIP).
      In both TD-ALTADENA and the TD-PASADENA strong spin echoes could be detected
      under conditions when usually no anti-phase signals can be measured due to the
      lack of resolution. The results suggest that the time-domain detection of PHIP
      enhanced signals opens up new application areas for low-field PHIP
      hyperpolarization, such as non-invasive compound detection or new contrast agents
      and biomarkers in low-field Magnetic Resonance Imaging (MRI). Finally, solid
      state NMR calculations are presented, which show that the solid echo (90y-tau-90x
      tau) version of the TD-ALTADENA experiment is able to convert up to 10% of the
      PHIP signal into visible magnetization.

PMID- 22365289
TI  - Is cryotherapy the optimal technology for ablation of lung tumors?

PMID- 22365290
TI  - From good to good deal: value-focused research.

PMID- 22365291
TI  - Nationwide trends in abdominal aortic aneurysm repair and use of endovascular
      repair in the emergency setting.
AB  - PURPOSE: To analyze nationwide trends in abdominal aortic aneurysm (AAA) repair
      and the use of endovascular abdominal aortic aneurysm repair (EVAR) in the
      emergency setting. MATERIALS AND METHODS: Data were obtained from the Nationwide
      Inpatient Sample (NIS) using the International Classification of Diseases, Ninth
      Revision-Clinical Modification (ICD-9-CM) codes for open and endovascular repairs
      from 2001-2009. Trends in outcome parameters and hospital charges were compared.
      RESULTS: The number of emergency EVAR procedures increased from 382 in 2001 to
      1,247 in 2009 (P < .001). During the study period, length of hospital stay
      associated with total number of EVAR procedures decreased from 3.8 days to 3.4
      days (P < .05), and the in-hospital mortality decreased from 2.4% to 2% (P =
      .32). From 2001-2009, mean hospital charges associated with EVAR increased from
      $50,630 to $91,401 (74% increase), whereas charges associated with open repairs
      increased from $54,578 to $128,925 (136% increase). The proportion of patients
      needing rehabilitation or nursing home placement after EVAR increased from 5.8%
      to 7.7% (P < .01), and need for home health increased from 6.9% to 10.5% (P <
      .01). CONCLUSIONS: There was a significant increase in the number of emergency
      EVAR procedures during the study period; however, the overall in-hospital
      mortality associated with EVAR remained unchanged, and the length of hospital
      stay showed a decreasing trend. The total hospital charges for EVAR were lower
      than the charges for open abdominal aneurysm repair throughout the study period;
      the difference in charges between the procedures showed a significant increasing
      trend with time.

PMID- 22365292
TI  - Commentary on "nationwide trends in abdominal aortic aneurysm repair and use of
      endovascular repair in the emergency setting".

PMID- 22365293
TI  - Commentary on "nationwide trends in abdominal aortic aneurysm repair and use of
      endovascular repair in the emergency setting".

PMID- 22365294
TI  - Increased complexity and complications associated with multiple peripherally
      inserted central catheter insertions in children: the tip of the iceberg.
AB  - PURPOSE: To assess the effects of repeated placements of peripherally inserted
      central catheters (PICCs) on the venous system in children. MATERIALS AND
      METHODS: Children who underwent successful first-time PICC placements between
      2005 and 2007 were retrospectively evaluated. Patient demographics, procedural
      data, and complications were obtained from hospital databases. Data from
      subsequent PICC insertions were compared with those from previous PICC
      insertions. A generalized estimating equation was used with appropriate
      statistical tests for data analysis. RESULTS: PICCs were grouped into four
      groups: first PICCs (n = 1,274), second PICCs (n = 167), third PICCs (n = 52),
      and fourth to seventh PICCs (n = 32). Successive PICCs were associated with
      progressively increased difficulty of access compared with earlier PICCs, as
      demonstrated by significant increases in procedural duration (P = .01) and
      fluoroscopy time (P = .005). Increased complexity was also evident through
      significant increases in the percentages of cases that required
      venography/digital subtraction angiography (P <.0001), multiple attempts to gain
      venous access (P <.0001), and a switch to another limb for venous access (P
      <.0001) between subsequent and first PICCs. In addition, rates of procedural
      complications also increased for subsequent PICCs compared with first PICCs (P
      <.0001). Furthermore use of the most preferred vein for vascular access
      significantly decreased in subsequent versus first PICC insertions (P <.0001).
      CONCLUSIONS: Increased procedural complexity and complications were found with
      successive PICC insertions. These results confirm the need for a prospective
      study to directly assess the long-term effects of PICCs on venous patency.

PMID- 22365295
TI  - Totally implantable venous access device placement by interventional
      radiologists: are prophylactic antibiotics necessary?
AB  - PURPOSE: To determine the rate of early infection for totally implantable venous
      access devices (TIVADs) placed without antibiotic prophylaxis. MATERIAL AND
      METHODS: A list of patients who underwent TIVAD placement in 2009 was obtained
      from the patient archiving and communication system (PACS). This list was cross
      referenced to all patients who underwent TIVAD removal from January 1, 2009,
      through January 30, 2010, to identify TIVADs that were removed within 30 days of
      placement. Retrospective chart review was performed to record patient
      demographics, including age, sex, cancer diagnosis, and indication for removal.
      Concurrent antibiotic therapy, chemotherapy, and laboratory data before and
      within 30 days of placement were recorded. Central line-associated bloodstream
      infections (CLABSIs) were identified using U.S. Centers for Disease Control and
      Prevention (CDC) criteria. RESULTS: There were 1,183 ports placed and 13 removed.
      CLABSIs occurred in seven (0.6%) patients within 30 days of placement. At the
      time of TIVAD placement, 81 (7%) patients were receiving antibiotics incidental
      to the procedure. One patient who received an antibiotic the day of implantation
      developed a CLABSI. Chemotherapy was administered to 148 (13%) patients on the
      day of placement. CONCLUSIONS: The rate of early infection without antibiotic
      prophylaxis before TIVAD placement in the interventional radiology suite is < 1%.
      Based on these data, use of prophylactic antibiotics for TIVAD placement is not
      recommended.

PMID- 22365296
TI  - Outcomes of percutaneous interventions for managing stenosis after meso-Rex
      bypass for extrahepatic portal vein obstruction.
AB  - PURPOSE: To determine outcomes in children with extrahepatic portal vein
      obstruction who underwent percutaneous intervention for anastomotic stenosis
      after meso-Rex bypass. MATERIALS AND METHODS: Eighty-six patients who underwent
      meso-Rex bypass between 1997 and 2009 were retrospectively reviewed, and 15 who
      underwent transhepatic portal venography for graft stenosis were identified.
      Technical success and clinical outcomes were analyzed. RESULTS: Nine of 15
      patients (60%) with anastomotic stenosis were successfully treated by
      endovascular techniques and remain symptom-free with patent shunts, three (20%)
      underwent technically successful interventions but currently have recurrent
      stenosis, and three (20%) underwent failed attempts at percutaneous intervention.
      All three in whom percutaneous intervention failed required surgical revision,
      including two with near-occlusive lesions that prevented traversal of the
      stenosis and one who developed postprocedure shunt thrombosis. In total, patients
      underwent 27 endovascular procedures, including 17 balloon venoplasties, four
      cutting balloon venoplasties, five stent placements, and one balloon venoplasty
      with thrombolysis. The mean pressure gradient across the stenosis decreased from
      11 mm Hg +/- 3 to 5 mm Hg +/- 3 (P < .001) after technically successful
      intervention. Platelet count improved (from 97,000/MUL +/- 41,000 to 165,000 +/-
      67,000/MUL; P = .002) and ammonia levels decreased (from 40 MUmol/L +/- 11 to 24
      MUmol/L +/- 13; P = .05) after intervention. Patients were followed for a median
      duration of 39 months after the last intervention. CONCLUSIONS: Percutaneous
      interventions allow for long-term vein graft patency and clinical resolution of
      symptoms in the majority of patients with anastomotic stenosis after meso-Rex
      bypass.

PMID- 22365297
TI  - Animal models in hepatocellular carcinoma: another step in the right direction.

PMID- 22365298
TI  - Vena cava filter scaffold to prevent migration of embolic materials in the
      treatment of a massive renal arteriovenous malformation.
AB  - Transcatheter occlusion of high-flow arteriovenous malformations (AVMs) or
      arteriovenous fistulas may be complicated by migration of embolic materials
      intended to impede flow. Reducing antegrade flow during catheter embolization via
      balloon occlusion or inhibiting migration with anchoring devices may improve
      procedural safety in high-flow settings. We describe the use of an inferior vena
      cava filter as a scaffold to support complete vascular occlusion of a large renal
      AVM.

PMID- 22365300
TI  - Pyomyoma after uterine artery embolization.

PMID- 22365299
TI  - Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: successful
      treatment with embolization and vincristine in two newborns.
AB  - Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor and has a high
      mortality in newborns when associated with Kasabach-Merritt syndrome (KMS). In
      two newborns with KHE and severe KMS refractory to medical treatment, emergency
      embolization led to clinical improvement in the acute neonatal setting by
      reducing tumor volume, increasing the platelet count, and improving other
      clotting parameters. Systemic vincristine treatment was added for further tumor
      control. Both patients remained symptom-free at long-term follow-up.

PMID- 22365301
TI  - Combined endovascular thrombolysis and uterine fibroid embolization in a patient
      with dural venous sinus thrombosis and severe metrorrhagia.

PMID- 22365302
TI  - Persistent primitive hypoglossal artery (a normal variant) as the sole supply to
      the brain.

PMID- 22365303
TI  - Therapeutic ureteral occlusion with n-butyl cyanoacrylate glue and an AMPLATZER
      plug scaffold.

PMID- 22365304
TI  - Uterine artery embolization for the treatment of adenomyosis: questions for long
      term efficacy.

PMID- 22365305
TI  - Leave no sponge uncounted.

PMID- 22365308
TI  - Expression of Toll-like receptors and downstream genes in lipopolysaccharide
      induced porcine alveolar macrophages.
AB  - The aim of the present study was to determine the age-related kinetic changes of
      Toll-like receptors (TLRs) and downstream genes expression, and secretion of
      cytokine in lipopolysaccharide (LPS) stimulated porcine alveolar macrophages
      (AM). For this purpose, AMs were isolated from 5-day-old newborn piglets and 120
      day-old young pigs. mRNA expression and cytokine measurement was determined by
      quantitative real-time PCR and ELISA, respectively. First, AMs were incubated for
      24 h in the absence or presence of increasing concentrations of LPS. Results
      showed the up-regulation of TLRs 2, 4, 5 and 9 mRNA from all concentrations of
      LPS used, as compared to non-stimulated cells, and TLR4 was the highest
      expression in both ages (P<0.05). Furthermore, quantitative analysis demonstrated
      increased expression of mRNAs encoding TLRs 2, 4, 5 and 9, LBP, CD14, MD2, MyD88,
      IRAK4 and TRAF6 in both ages in a time-dependant manner (P<0.05). Overall, LPS
      inducible mRNA for TLR4, LBP, CD14 and MyD88 had higher expression in newborn
      piglets compared with those of young pigs (P<0.05). The level of cytokine protein
      IL6 and TNFalpha in supernatant fluid significantly varied with time of
      incubation and age of animals. Their concentration increased immediately at 1 h
      after LPS stimulation and remained significantly higher up to 48 h in both ages.
      Production of pro-inflammatory cytokine protein IL6 and TNFalpha in supernatant
      was significantly higher in young pigs than those of piglets. This study suggests
      that differential age-related changes in the expression of TLRs and downstream
      genes, and pro-inflammatory cytokine could contribute to a different age-related
      innate immune response during pulmonary infection. Further investigation is
      warranted to determine the precise effects of LPS on porcine AMs by means of a
      functional study across a wider age range.

PMID- 22365309
TI  - Imaging the neural correlates of neuropathic pain and pleasurable relief
      associated with inherited erythromelalgia in a single subject with quantitative
      arterial spin labelling.
AB  - We identified a patient with severe inherited erythromelalgia secondary to an
      L858F mutation in the voltage-gated sodium channel Na(v)1.7. The patient reported
      severe ongoing foot pain, which was exquisitely sensitive to limb cooling. We
      confirmed this heat hypersensitivity using quantitative sensory testing.
      Additionally, we employed a novel perfusion imaging technique in a simple block
      design to assess her baseline erythromelalgia pain vs cooling relief. Robust
      activations of key pain, pain-affect, and reward-related centres were observed.
      This combined approach allowed us to confirm the presence of a temperature
      sensitive channelopathy of peripheral neurons and to investigate the neural
      correlates of tonic neuropathic pain and relief in a single subject.

PMID- 22365310
TI  - Pain affect in the absence of pain sensation: evidence of asomaesthesia after
      somatosensory cortex lesions in the rat.
AB  - Multidimensional models of pain processing distinguish the sensory, motivational,
      and affective components of the pain experience. Efforts to understand underlying
      mechanisms have focused on isolating the roles of specific brain structures,
      including both limbic and non-limbic cortical areas, in the processing of
      nociceptive stimuli. The purpose of this study was to examine the role of the
      somatosensory cortex in both sensory and affective aspects of pain processing. It
      was hypothesized that animals with lesions of the hind limb area of the
      somatosensory cortex would demonstrate altered sensory processing (asomaesthesia,
      a deficit in the ability to detect and identify somatic sensation) in the
      presence of an inflammatory state when compared to animals with sham lesions. The
      level of pain affect produced by an inflammatory pain condition was not expected
      to change, as this region has not demonstrated a role in processing the affective
      component of pain. Seventy-nine adult female Sprague-Dawley rats were randomly
      assigned to receive bilateral lesions or a sham procedure. The results showed
      that somatosensory lesions to the hindlimb region altered responses to mechanical
      stimulation in the presence of experimentally-induced inflammation, but did not
      attenuate the inflammation-induced paw volume changes or the level of pain
      affect, as demonstrated by escape/avoidance behavior in response to mechanical
      stimulation. Overall, these results support previous evidence suggesting that the
      somatosensory cortex is primarily involved in the processing the
      sensory/discriminative aspect of pain, and the current study is the first to
      demonstrate the presence of pain affect in the absence of somatosensory
      processing.

PMID- 22365311
TI  - Pain and the primary somatosensory cortex.

PMID- 22365312
TI  - Metabolite movement across the schistosome surface.
AB  - Intravascular schistosome parasites are covered by an unusual double lipid
      bilayer. Nutrients, such as glucose and amino acids, as well as other
      metabolites, are known to be transported across this surface via specific
      transporter proteins. For instance, the glucose transporter protein SGTP4 is
      found in the host-interactive tegumental membranes. A second glucose transporter,
      SGTP1, localizes to the tegumental basal membrane (and internal tissues).
      Following expression in Xenopus oocytes, SGTP1 and SGTP4 both function as
      facilitated-diffusion sugar transporters. Suppressing the expression of SGTP1 and
      SGTP4 in juvenile schistosomes using RNA interference (RNAi) impairs the
      parasite's ability to import glucose and severely decreases worm viability. Amino
      acids can also be imported into schistosomes across their surface and an amino
      acid transporter (SPRM1lc) has been localized in the parasite surface membranes
      (as well as internally). In Xenopus oocytes, SPRM1lc can import the basic amino
      acids arginine, lysine and histidine as well as leucine, phenylalanine,
      methionine and glutamine. To function, this protein requires the assistance of a
      heavy-chain partner (SPRM1hc) which acts as a chaperone. Water is transported
      across the tegument of schistosomes via the aquaporin protein SmAQP. Suppressing
      SmAQP gene expression makes the parasites less able to osmoregulate and decreases
      their viability. In addition, SmAQP-suppressed adult parasites have been shown to
      be impaired in their ability to excrete lactate. Analysis of tegumental
      transporter proteins, as described in this report, is designed to generate a
      comprehensive understanding of the role of such proteins in promoting parasite
      survival by controlling the movement of metabolites into and out of the worms.

PMID- 22365313
TI  - Aspirin desensitization in patients undergoing planned or urgent coronary stent
      implantation. A single-center experience.
AB  - INTRODUCTION: Dual antiplatelet therapy (aspirin and ADP-antagonists) is
      mandatory after stent implantation in order to avoid stent thrombosis, especially
      in the era of DES. In fact, a delayed re-endothelization process may enlarge the
      window of occurrence of stent thrombosis beyond 1-year after implantation.
      Allergy to acid acetylsalicylic is not a rare event and may influence the use and
      the choice of coronary stent with an important impact in terms of outcome
      especially in patients at high risk for in-stent restenosis. The aim of this
      study was to evaluate the safety and efficacy of a new intravenous rapid
      desensitization protocol in patients with acetylsalicylic acid sensitivity
      undergoing coronary stent implantation. METHODS: Among a total of 1385 patients
      undergoing coronary angioplasty at our catheterization laboratory from January
      2007 to June 2011, a total of 43 patients (3.1%) had history of aspirin
      sensitivity characterized by respiratory or cutaneous manifestations (none had
      previous anaphylactic reactions). Twenty-three patients (53.5%) presented with
      acute coronary syndromes. All patients underwent a novel rapid desensitization
      procedure before or after cardiac catheterization (in case of ST-elevation
      myocardial infarctions, n=5). The desensitization procedure was based on
      intravenous administration of 9 sequential doses of aspirin (1, 2, 4, 8, 16, 32,
      64, 128, 250 mg) over 4.5h without the use of corticosteroids or antihistamines.
      Patients were followed for at least 30 days and up to 12 months to assess
      compliance with aspirin therapy and adverse events. RESULTS: The desensitization
      procedure was successful in 42 patients (97.6%). All patients underwent stent
      implantation (1.6 stents/patient). Drug-eluting stents were used in 36 patients
      (85.7%). At follow-up, all patients who successfully responded to the
      desensitization procedure did not develop any allergic reaction. CONCLUSIONS:
      This study showed the safety and efficacy of a new rapid intravenous protocol
      desensitization for patients with history of aspirin sensitivity undergoing
      planned or urgent coronary stent implantation.

PMID- 22365314
TI  - Glycemic improvement normalizes myocardial microvascular reserve in type 2
      diabetes.

PMID- 22365315
TI  - Quantification of left ventricular regional myocardial function using two
      dimensional speckle tracking echocardiography in healthy volunteers--a multi
      center study.
AB  - BACKGROUND: Although two-dimensional speckle tracking (2DST) has been validated
      in animal and early clinical studies for quantitative evaluation of myocardial
      motion and contractility, there are only limited measurements in large healthy
      population to be used as reference data, which severely restricts its clinical
      application. This study aimed at determining the age-specific normal values of
      left ventricular (LV) longitudinal, circumferential and radial strain in healthy
      adults. METHODS: We studied 228 healthy subjects (109 males, mean age 44 +/- 15
      years, range 18-78 years). Their LV longitudinal, circumferential and radial
      strains were measured by 2DST at basal, middle and apical levels of parasternal
      short-axis and apical 2-, 4- and 3-chamber views. The effects of age, gender and
      echocardiographic machines (52 patients had measurements obtained by both GE and
      Philips machines) on these parameters were also evaluated. RESULTS: The
      longitudinal and circumferential strains were -20.4 +/- 3.4% and -22.9 +/- 3.1%,
      respectively with higher values being observed at basal than apical segments. On
      the contrary, the radial strain which ranged 42.6 +/- 12.9% decreased towards
      apical segments. The longitudinal strain declined, the circumferential strain
      rose and the radial strain remained similar during aging. Adult females had
      slightly higher circumferential and longitudinal strains than males (23 +/- 3% vs
      -22 +/- 3%, -21 +/- 3% vs -20 +/- 3% respectively; both p<0.01). Strains measured
      by the 2 different echo machines had good correlations but Phillips-assessed
      strains (longitudinal and circumferential) were 10% higher than GE measurements.
      Inter- and intra-observer variabilities were acceptable. CONCLUSIONS: Strain
      measurements by 2DST echocardiography varies with age, gender and
      echocardiographic vendors in healthy adults. These findings are important to
      differentiate between health and disease and to assess the severity of disease.

PMID- 22365316
TI  - Acute bilateral posterior dislocation of the shoulder: one-stage reconstruction
      of both humeral heads with cancellous autograft and cartilage preservation.
AB  - We present a case of bilateral posterior shoulder dislocation after an epileptic
      seizure. The anterior humeral-head impression fracture was 60% of the articular
      surface on the right shoulder and 30% on the left shoulder. We performed an early
      one-stage reconstruction of both humeral heads. A cancellous autograft was used
      on the left side and an iliac cortico-cancellous autograft on the right side,
      with preservation of the patient's cartilage. Three years later, the clinical and
      morphological results were excellent. The discussion focuses on surgical options
      that range from conservative treatment with excision of the damaged cartilage to
      immediate hemiarthroplasty. This case is original because of the preservation of
      the patient's cartilage during reconstruction.

PMID- 22365317
TI  - [Preiser's disease: a five-case series].
AB  - Preiser's disease, or avascular necrosis of the scaphoid occurs without fracture
      or non-union. Between 1998 and 2009, the authors report on 5 patients who
      complained of mild pain on the radial aspect of the wrist, associated with
      stiffness and/or loss of strength. Our management consisted in different options:
      one bilateral intraarticular injection of hyaluronic acid, three vascularised
      radial bone graft and one resection of the first carpal row. With four and a half
      years follow-up, our results are quite satisfactory for improvement of pain,
      sometimes with residual postoperative stiffness. Management remains difficult
      because Preiser's disease is rare and there are no relevant prospective control
      studies. We attempt to provide an algorithm for early management of the disease
      and to answer the question: "until when can we save the scaphoid and how?"

PMID- 22365318
TI  - [Scaphoidectomy (instead of trapezectomy) in the treatment of rhizoarthrosis.
      Report of a case].
AB  - INTRODUCTION: Surgery site errors and technical errors in hand surgery are rare
      and not often published. OBSERVATION: A 46-year-old patient with rhizoarthrosis
      of the left hand was initially treated by mistake in another center by a
      scaphoidectomy instead of a trapezectomy. She was seen in consultation 6months
      later, still suffering from her rhizoarthrosis and with carpal instability,
      clinically symptomatic and radiologically confirmed. The instability of the wrist
      was treated by a hamatocapito-lunar arthrodesis and a trapeziometacarpal
      arthrodesis was performed to treat the rhizoarthrosis. The clinical and
      radiological results were acceptable. DISCUSSION: Besides the paradigmatic error,
      this observation confirms that the excision of the scaphoid quickly leads to a
      destabilization of the wrist, the capitatum no longer maintaining its alignment
      under the lunatum, and leads to a limitation of the wrist mobility and a loss of
      strength. The hamato-capito-lunate arthrodesis described in 1997 can treat wrist
      instability and only the trapeziometacarpal arthrodesis can, in the absence of
      scaphoid, treat the problem of rhizoarthrosis. CONCLUSION: The authors recommend
      to always carry out a radiography of the wrist during trapezectomy surgery when
      there is doubt about the identification of the trapezium.

PMID- 22365319
TI  - Thumb metacarpophalangeal joint ligament reconstruction with a triangular tendon
      graft in posttraumatic chronic instability.
AB  - The purpose of this study was to report the results of static triangular ligament
      reconstruction, in thumb metacarpophalangeal (MCP) joint chronic posttraumatic
      laxity using a tendon graft with a proximal apex in ten patients. The mean
      postoperative follow-up was 40.2 months. The mean postoperative thumb MCP joint
      stress testing was 43 degrees  less than before surgery, and 6.5 degrees  less
      than in the non-injured hand. The mean range of flexion was 10.5 degrees  lower
      in the operated thumb than in the contralateral one, and the mean range of
      extension was 8 degrees  lower. Minimal differences in the values of the Kapandji
      score, grip and key-pinch strength were found. The preoperative pain became an
      occasional discomfort after surgery. All patients had a subjective sense of
      stability until final follow-up. All patients returned to their work or daily
      activities. LEVEL OF EVIDENCE IV: For therapeutic studies investigating the
      results of treatment.

PMID- 22365320
TI  - Brachial plexus endoscopy: feasibility study on cadavers.
AB  - The development of a minimally invasive technique for exploration of the brachial
      plexus seems a logical step towards refinement of diagnosis and treatment. For
      certain pathological conditions, minimally invasive techniques have become the
      method of choice; for others, they remain as an ancillary option for assistance
      during open surgery. We have developed a full endoscopic technique for brachial
      plexus exploration. Our endoscopic technique used saline liquid infusion in seven
      brachial plexus of four cadavers. Five portals have been described and the
      endoscopic landmarks also. We were able to demonstrate excellent views and
      adequate possibilities for cadaver plexus dissection and its anatomic landmarks
      and portals. LEVEL OF EVIDENCE: 4.

PMID- 22365321
TI  - Evaluation of factors influencing confidence and trust in the patient-physician
      relationship: a survey of patient in a hand clinic.
AB  - OBJECTIVES: The purpose of this study was to identify the skills found most
      important to gain patient's trust from a patient's perspective. METHODS: One
      hundred and twenty-two patients were surveyed prospectively using a questionnaire
      assessing professionalism, physical environment, verbal and non-verbal
      communication skills. Factors required to establish a trusting patient-surgeon
      relationship were ranked in order of importance before and after initial
      consultation with a surgeon in a hand surgery clinic model. RESULTS: No
      significant relationship was identified between gender, age, education or income,
      and answers provided by respondents. Technical ability, verbal communication
      skills and respect of patient's autonomy by the physician were found most
      important. CONCLUSION: The visit with the surgeon significantly affected the
      ranking of some of the skills deemed important. Patients view respect of autonomy
      and verbal communication skills as the most important attributes when developing
      trust and confidence in a surgeon, followed by technical proficiency.

PMID- 22365322
TI  - [Reproducibility study of the "400 Points assessment", a measurement of the
      hand's functional ability].
AB  - OBJECTIVES: Evaluate the inter-rater and test-retest reproducibility of the "400
      Points assessment", a measurement of the functional ability of the hand. The
      scale included four tests: function of the hand, prehension strengths, handling
      and displacement of things, and function with both hands. METHODS: Thirty
      patients with hand injuries were participated. The inter-rate agreements were
      examinated between three occupational therapists. The First rater was an
      experienced user of this instrument (observer 1), the second one was a novice
      user (observer 2), the last rater is a student who had never used it before
      (observer 3). Subjects were tested twice by the same raters independently, with
      30 minutes intervals between tests. Statistical analysis was done by calculating
      average differences and intraclass correlation coefficient. RESULTS: (i) The
      difference between the three raters agreements was small for the two
      measurements, except for function with both hands in the second period. Every
      intraclass correlation coefficient was higher than 0.95. (ii) Difference between
      the two measurements was small for every observer. These differences are not
      significant except for function with both hands. Intraclass correlation
      coefficients are all higher than 0.82 even than 0.90 for the total score. The
      difference between the two periods for the overall test is small, from 5% to 10%
      for seven patients and from 10 to 15% for two patients. Differences at two times
      had the same agreement for the three observers. CONCLUSION: "400 Points
      assessment" is reproducible (inter-rater and test-retest reproductibility). The
      test "function with both hands" requires more experience of the assessment.

PMID- 22365324
TI  - The effect of various topical peri-implantitis antiseptics on Staphylococcus
      epidermidis, Candida albicans, and Streptococcus sanguinis.
AB  - OBJECTIVE: Although peri-implantitis has presented an ever increasing problem in
      modern dentistry, satisfying therapeutic strategies or scientifically based
      treatment recommendations are still not available. The main object of the present
      study was to evaluate the antibacterial efficacy of six different topical
      antiseptics on three test microorganisms attached to titanium implant specimens.
      MATERIAL AND METHODS: For biofilm formation, plane titan specimens were incubated
      either in Candida albicans, Streptococcus sanguinis, or Staphylococcus
      epidermidis for 2h. The specimens were then treated with different topical
      antiseptics for 60s (sodium hypochlorite 1.0%, hydrogen peroxide 3.0%,
      chlorhexidine gluconate 0.2%, citric acid 40.0%, Plax, or Listerine) and with
      sterile saline as control. Remaining vital fungi were quantified by means of a
      bioluminometric assay and the bacterial load and the viability of adhering S.
      epidermidis and S. sanguinis by live or dead cell labelling in combination with
      fluorescence microscopy. RESULTS: Sodium hypochlorite was effective against all
      three species, whereas hydrogen peroxide was solely effective against C.
      albicans. CHX and Listerine showed antimicrobial activity against S. sanguinis
      and C. albicans and citric acid and Plax against both tested bacteria.
      CONCLUSIONS: None of the tested antimicrobial agents, except for sodium
      hypochlorite, showed a significant in vitro effect on all three test microbes.
      Considering the possible toxicity of sodium hypochlorite, none of the tested -
      and so far widely used - antiseptics showed any broad-spectrum antimicrobial
      effect and could therefore not be recommended for the topical disinfection and
      detoxification of infected implant surfaces.

PMID- 22365323
TI  - A prospective study of nosocomial-infection-related mortality assessed through
      mortality reviews in 14 hospitals in Northern France.
AB  - AIM: To determine the number of deaths associated with nosocomial infection (NI)
      occurring in French hospitals, and to evaluate the role of hospital mortality
      reviews in assessing the preventability of NI-associated death. METHODS: The
      study considered 13,537 consecutive deaths occurring in 14 French hospitals in
      2007 and 2008. An expert commission including attending physicians and nurses
      determined the likelihood that deaths could be attributed to NI, and the
      preventability of NI and death. FINDINGS: Medical records of the 2355 eligible
      patients with a McCabe score of 0 or 1 who died more than 48 h after admission
      were reviewed. Among them, 33% had at least one NI. Death was attributable to NI
      in 182 patients, and was considered preventable in 35 cases. Among these, 10
      deaths were unexpected. CONCLUSION: Extrapolating these figures nationally,
      approximately 3500 [95% confidence interval (CI) 2605-4036] deaths attributable
      to NI occur in France annually. Among these, approximately 1300 NIs (95% CI 357
      2196) and 800 deaths (95% CI 51-1481) can be considered preventable. Hospital
      mortality review commissions can help to improve the quality of health care by
      identifying circumstances associated with NI contributing to death, and targeting
      specific preventative measures. Such hospital commissions should involve all
      healthcare personnel.

PMID- 22365325
TI  - Internally deleted WNV genomes isolated from exotic birds in New Mexico: function
      in cells, mosquitoes, and mice.
AB  - Most RNA viruses exist in their hosts as a heterogeneous population of related
      variants. Due to error prone replication, mutants are constantly generated which
      may differ in individual fitness from the population as a whole. Here we
      characterize three WNV isolates that contain, along with full-length genomes,
      mutants with large internal deletions to structural and nonstructural protein
      coding regions. The isolates were all obtained from lorikeets that died from WNV
      at the Rio Grande Zoo in Albuquerque, NM between 2005 and 2007. The deletions are
      approximately 2kb, in frame, and result in the elimination of the complete
      envelope, and portions of the prM and NS-1 proteins. In Vero cell culture, these
      internally deleted WNV genomes function as defective interfering particles,
      reducing the production of full-length virus when introduced at high
      multiplicities of infection. In mosquitoes, the shortened WNV genomes reduced
      infection and dissemination rates, and virus titers overall, and were not
      detected in legs or salivary secretions at 14 or 21 days post-infection. In mice,
      inoculation with internally deleted genomes did not attenuate pathogenesis
      relative to full-length or infectious clone derived virus, and shortened genomes
      were not detected in mice at the time of death. These observations provide
      evidence that large deletions may occur within flavivirus populations more
      frequently than has generally been appreciated and suggest that they impact
      population phenotype minimally. Additionally, our findings suggest that highly
      similar mutants may frequently occur in particular vertebrate hosts.

PMID- 22365327
TI  - Avian influenza A virus PB2 promotes interferon type I inducing properties of a
      swine strain in porcine dendritic cells.
AB  - The 2009 influenza A virus (IAV) pandemic resulted from reassortment of avian,
      human and swine strains probably in pigs. To elucidate the role of viral genes in
      host adaptation regarding innate immune responses, we focussed on the effect of
      genes from an avian H5N1 and a porcine H1N1 IAV on infectivity and activation of
      porcine GM-CSF-induced dendritic cells (DC). The highest interferon type I
      responses were achieved by the porcine virus reassortant containing the avian
      polymerase gene PB2. This finding was not due to differential tropism since all
      viruses infected DC equally. All viruses equally induced MHC class II, but
      porcine H1N1 expressing the avian viral PB2 induced more prominent nuclear NF
      kappaB translocation compared to its parent IAV. The enhanced activation of DC
      may be detrimental or beneficial. An over-stimulation of innate responses could
      result in either pronounced tissue damage or increased resistance against IAV
      reassortants carrying avian PB2.

PMID- 22365326
TI  - Point mutations in the West Nile virus (Flaviviridae; Flavivirus) RNA-dependent
      RNA polymerase alter viral fitness in a host-dependent manner in vitro and in
      vivo.
AB  - The West Nile virus (WNV) genome contains a single RNA-dependent RNA polymerase
      (RdRp) gene, which is responsible for replication of the viral genome and, as
      such, is an important target for antiviral therapy. Viral RdRps are known to lack
      proofreading capabilities and as a result viruses such as WNV exist as a mixture
      of viral genotypes within an infection, enabling the virus to readily emerge and
      adapt to new host environments. To test the consequences of subtle structural
      alterations remote from the RdRp active-site, the following single point
      mutations were engineered in the WNV NS5 RdRp coding region: T363N, A365N, and
      T537I; these mutations were selected in an effort to stabilize the secondary
      structural elements near the rNTP binding pocket of the RdRp. Mutant viruses were
      tested in vitro on Vero, C6/36, Culex tarsalis and DF-1 cell types and in vivo in
      one day old chickens and Culex pipiens mosquitoes. Plaque morphology was affected
      by each mutation and growth and RNA replication kinetics were altered as well.
      Our results demonstrate that subtle alteration of the RdRp protein away from the
      active site can have a significant overall biological effect on WNV fitness, and
      that this effect can be host-dependent.

PMID- 22365329
TI  - Neural network and multiple linear regression to predict school children
      dimensions for ergonomic school furniture design.
AB  - The current study investigates the possibility of obtaining the anthropometric
      dimensions, critical to school furniture design, without measuring all of them.
      The study first selects some anthropometric dimensions that are easy to measure.
      Two methods are then used to check if these easy-to-measure dimensions can
      predict the dimensions critical to the furniture design. These methods are
      multiple linear regression and neural networks. Each dimension that is deemed
      necessary to ergonomically design school furniture is expressed as a function of
      some other measured anthropometric dimensions. Results show that out of the five
      dimensions needed for chair design, four can be related to other dimensions that
      can be measured while children are standing. Therefore, the method suggested here
      would definitely save time and effort and avoid the difficulty of dealing with
      students while measuring these dimensions. In general, it was found that neural
      networks perform better than multiple linear regression in the current study.

PMID- 22365328
TI  - MuLV IN mutants responsive to HDAC inhibitors enhance transcription from
      unintegrated retroviral DNA.
AB  - For Moloney murine leukemia virus (M-MuLV), sustained viral infections require
      expression from an integrated provirus. For many applications, non-integrating
      retroviral vectors have been utilized to avoid the unwanted effects of
      integration, however, the level of expression from unintegrated DNA is
      significantly less than that of integrated provirus. We find that unintegrated
      DNA expression can be increased in the presence of HDAC inhibitors, such as TSA,
      when applied in combination with integrase (IN) mutations. These mutants include
      an active site mutation as well as catalytically active INs bearing mutations of
      K376 in the MuLV C-terminal domain of IN. MuLV IN K376 is homologous to K266 in
      HIV-1 IN, a known substrate for acetylation. The MuLV IN protein is acetylated by
      p300 in vitro, however, the effect of HDAC inhibitors on gene expression from
      unintegrated DNA is not dependent on the acetylation state of MuLV IN K376.

PMID- 22365332
TI  - Global transcription analysis of vaccinated channel catfish following challenge
      with virulent Edwardsiella ictaluri.
AB  - To determine the identities of genes involved in either innate or adaptive
      immunity, microarray analysis of 65,182 UniGene transcripts were performed to
      compare gene expression in vaccinated channel catfish after challenge with a
      virulent Edwardsiella ictaluri compared to that in sham-vaccinated fish without
      challenge. With a filter of false-discovery rate less than 0.05 and fold change
      greater than 2, a total of 167 functionally known unique transcripts were found
      to be up-regulated, whereas 40 were down-regulated. The 167 up-regulated
      transcripts represent genes with putative functions in the following eight major
      categories: (1) immunity (30%); (2) metabolism and energy production (22%); (3)
      transcription or translation (12%); (4) protein degradation (11%); (5) signal
      transduction (6%); (6) traffic and transport (6%); (7) cell structure or cell
      cycle (8%); and (8) others (5%). The 40 down-regulated transcripts represent
      genes with putative functions in the following six major categories: (1)
      metabolism (27.5%); (2) immunity (17.5%); (3) cell structure (17.5%); (4) cell
      motility (10%); (5) signal transduction (15%); and (6) others (12.5%). Microarray
      analysis revealed that lysozyme c was up-regulated the most (70-fold) in
      vaccinated fish at 48 h post challenge of virulent E. ictaluri whereas
      myotubularin related protein 1a and cytochrome P450 2J27 were down-regulated the
      most (8.1 fold). Differential regulation of eight randomly selected transcripts
      in vaccinated fish after challenge with virulent E. ictaluri was also validated
      by quantitative PCR. Our results suggest that these differentially regulated
      genes might play important roles in channel catfish immunity against E. ictaluri.

PMID- 22365331
TI  - Analysis of herbal dietary supplements for sexual performance enhancement: first
      characterization of propoxyphenyl-thiohydroxyhomosildenafil and identification of
      sildenafil, thiosildenafil, phentolamine and tetrahydropalmatine as adulterants.
AB  - Nine herbal dietary supplements intended to be beverages for enhancing sexual
      performance were analyzed before their possible launch on the market. Four of
      them contained a sildenafil analog reported for the first time as an adulterant.
      After isolation and characterization using NMR, MS, IR and UV, this analog was
      named propoxyphenyl-thiohydroxyhomosildenafil as the ethoxy chain on the phenyl
      ring of the already known analog thiohydroxyhomosildenafil was replaced by a
      propoxy moiety. One formulation was tainted with thiosildenafil, another
      unapproved PDE-5 inhibitor. Sildenafil along with the natural alkaloid
      tetrahydropalmatine that has no documented effect for enhancing erectile
      dysfunction were identified in two formulations. Another formulation was
      adulterated with phentolamine, a drug that is not approved for boosting male
      sexual performance when taken orally. The last formulation containing osthole, a
      bioactive natural coumarine improving sexual dysfunction, is most probably truly
      natural.

PMID- 22365330
TI  - Cellular senescence and cancer chemotherapy resistance.
AB  - Innate or acquired resistance to cancer therapeutics remains an important area of
      biomedical investigation that has clear ramifications for improving cancer
      specific death rates. Importantly, clues to key resistance mechanisms may lie in
      the well-orchestrated and highly conserved cellular and systemic responses to
      injury and stress. Many anti-neoplastic therapies typically rely on DNA damage,
      which engages potent DNA damage response signaling pathways that culminate in
      apoptosis or growth arrest at checkpoints to allow for damage repair. However, an
      alternative cellular response, senescence, can also be initiated when challenged
      with these internal/external pressures and in ideal situations acts as a self
      protecting mechanism. Senescence-induction therapies are an attractive concept in
      that they represent a normal, highly conserved and commonly invoked tumor
      suppressing response to overwhelming genotoxic stress or oncogene activation.
      Yet, such approaches should ensure that senescence by-pass or senescence re
      emergence does not occur, as emergent cells appear to have highly drug resistant
      phenotypes. Further, cell non-autonomous senescence responses may contribute to
      therapy-resistance in certain circumstances. Here we provide an overview of
      mechanisms by which cellular senescence plausibly contributes to therapy
      resistance and concepts by which senescence responses can be influenced to
      improve cancer treatment outcomes.

PMID- 22365333
TI  - Virus-specific CD8+ T-cells detected in PBMC from horses vaccinated against
      African horse sickness virus.
AB  - African horsesickness (AHS) is an infectious but noncontagious viral disease
      affecting all species of Equidae. The recall immune response of AHSV naive horses
      immunised with an attenuated African horsesickness virus serotype 4 (AHSV4) was
      characterised using immune assays including ELISPOT, real-time PCR (qPCR) and
      flow cytometry. The recall immune response detected in PBMC isolated from three
      inoculated horses showed an upregulation of circulating B lymphocytes that
      correlated with elevated IL-4 mRNA expression indicative of humoral immunity, but
      reduced frequency of CD4+ cells. In addition to the expected antibody response,
      an increase in CD8+ cells was also detected. Although these CD8+ cells may be
      CTL, the role of these cells in immunity against AHSV still has to be determined.

PMID- 22365334
TI  - Intracranial cotton ball gossypiboma mimicking recurrent meningioma: report of a
      case with literature review for intentional and unintentional foreign body
      granulomas.

PMID- 22365336
TI  - Endocranial volume of Australopithecus africanus: new CT-based estimates and the
      effects of missing data and small sample size.
AB  - Estimation of endocranial volume in Australopithecus africanus is important in
      interpreting early hominin brain evolution. However, the number of individuals
      available for investigation is limited and most of these fossils are, to some
      degree, incomplete and/or distorted. Uncertainties of the required reconstruction
      ('missing data uncertainty') and the small sample size ('small sample
      uncertainty') both potentially bias estimates of the average and within-group
      variation of endocranial volume in A. africanus. We used CT scans, electronic
      preparation (segmentation), mirror-imaging and semilandmark-based geometric
      morphometrics to generate and reconstruct complete endocasts for Sts 5, Sts 60,
      Sts 71, StW 505, MLD 37/38, and Taung, and measured their endocranial volumes
      (EV). To get a sense of the reliability of these new EV estimates, we then used
      simulations based on samples of chimpanzees and humans to: (a) test the accuracy
      of our approach, (b) assess missing data uncertainty, and (c) appraise small
      sample uncertainty. Incorporating missing data uncertainty of the five adult
      individuals, A. africanus was found to have an average adult endocranial volume
      of 454-461 ml with a standard deviation of 66-75 ml. EV estimates for the
      juvenile Taung individual range from 402 to 407 ml. Our simulations show that
      missing data uncertainty is small given the missing portions of the investigated
      fossils, but that small sample sizes are problematic for estimating species
      average EV. It is important to take these uncertainties into account when
      different fossil groups are being compared.

PMID- 22365337
TI  - ELISAs based on rNcGRA7 and rNcSAG1 antigens as an indicator of Neospora caninum
      activation.
AB  - Bovine abortion caused by the Apicomplexa parasite Neospora caninum is a major
      economical problem in the livestock industry worldwide. However, the relationship
      between N. caninum infection and abortion is still unknown. Our study aimed to
      elucidate the relationship between parasite-specific antibody responses, parasite
      stages and abortion. In experimentally infected cattle, anti-NcGRA7 IgG1 antibody
      was predominantly detected during the acute infection stage, while the production
      of anti-NcSAG1 IgG1 antibody was observed during both acute and chronic stages.
      Furthermore, levels of anti-NcGRA7 IgG2 antibody were lower than those of anti
      NcSAG1 IgG2 antibody. When tested on cattle with Neospora-associated abortion,
      positive rates of the anti-NcGRA7 IgG2 antibody were significantly lower than
      those of the anti-NcSAG1 antibody, although there was no difference in IgG1
      antibody-positive rates between the two antigens. In addition, anti-NcGRA7 IgG2
      antibodies were not detected in cattle for more than 30days after abortion. Our
      results suggested that anti-NcGRA7 and anti-NcSAG1 antibodies are suitable
      indicators for the activation stage of N. caninum infection and broad detection
      of the infection, respectively. In conclusion, the use of recombinant NcGRA7 and
      NcSAG1-based ELISAs will be useful for evaluating the abortion risk associated
      with N. caninum infection.

PMID- 22365338
TI  - A survey of ixodid ticks feeding on cattle and prevalence of tick-borne pathogens
      in the Black Sea region of Turkey.
AB  - The study reports the frequency of infestation and the prevalence of tick-borne
      pathogens in feeding adult ticks detached from cattle in two climatic zones of
      the Black Sea region of Turkey. A total of 2160 adult ticks were collected during
      2007-2008. Of these, 1062 were randomly selected, divided into 224 pools, and
      tested for the presence of bovine Theileria, Babesia, and Anaplasma species.
      Eleven tick species were recognized on cattle in the study. Hyalomma marginatum
      was widely disrubuted in the semi-arid bioclimatic zone, but few specimens were
      collected in the humid bioclimatic zone. The most prevalent tick species in the
      humid climatic zone was Ixodes ricinus. Infection rates were calculated as the
      maximum likelihood estimation with 95% confidence intervals (CI). Overall, 4% (CI
      2.87-5.44) of 224 tick pools were found to be positive for the pathoges by
      Reverse line blot. Maximum likelihood estimation of the infection rate varied
      among tick species, ranging from 2.68% (CI 0.16-12.68) in Haemaphysalis sulcata
      to 10.49% (CI 4.07-23.66) in Rhipicephalus bursa. The most prevalent tick-borne
      pathogen was Anaplasma phagocytophilum at 6.78% (CI 3.41-12.18) followed by A.
      centrale (6.56%, CI 0.42-31.47), Anaplasma/Ehrlichia spp. (3.61%, CI 1.99-6.06),
      Babesia spp. (3.33%, CI 1.65-6.03), and T. buffeli/orientalis (2.71%, CI 0.73
      7.18). Sequencing results indicated that Babesia spp. shared 99% to 100%
      similarity with the unnamed Babesia sp. Kashi 1 and 2, Babesia sp. Kayseri 1 and
      Babesia sp.CS58. Anaplasma/Ehrlichia spp. were 98% and 100% identical to
      Ehrlichia canis and Ehrlichia sp. Omatjenne strain, respectively.

PMID- 22365339
TI  - Developmental capacity of in vitro-matured human oocytes retrieved from
      polycystic ovary syndrome ovaries containing no follicles larger than 6 mm.
AB  - OBJECTIVE: To test the developmental competence of oocytes in a nonhCG-triggered
      in vitro maturation (IVM) system when oocyte-cumulus complexes (OCC) are
      retrieved from antral follicles with a diameter of <6 mm. DESIGN: Prospective
      cohort study. SETTING: Tertiary university-based referral center. PATIENT(S):
      From January 2010 to September 2011, 121 patients with polycystic
      ovaries/polycystic ovary syndrome underwent 239 IVM cycles in total. In 58 of
      these cycles (44 patients), all antral follicles had a diameter of <6 mm on the
      day of oocyte retrieval. INTERVENTION(S): NonhCG-triggered IVM of oocytes, fresh
      or vitrified/warmed embryo transfer (ET). MAIN OUTCOME MEASURE(S): Oocyte
      diameter, maturation rate, fertilization rate, embryo development and morphology,
      implantation rate, clinical pregnancy rate, ongoing pregnancy rate. RESULT(S):
      Oocyte retrieval yielded 16.7 OCC/cycle, and 50.8% of oocytes completed IVM. The
      mean oocyte diameter increased from 108.8 +/- 4.3 MUm to 111.9 +/- 4.1 MUm after
      IVM. Mean fertilization rate was 63.7%, and 45.4% of 2-pronuclei oocytes
      developed into a morphologically good-quality embryo on day 3 after
      intracytoplasmic sperm injection. Fresh ET resulted in two ongoing pregnancies
      (2/37; 5.4%). Deferred vitrified-warmed ET led to an ongoing pregnancy rate of
      34.6% (9/24). Three healthy babies were born and eight pregnancies were still
      ongoing. CONCLUSION(S): Oocytes retrieved from follicles with a diameter of <6 mm
      grow during a 40-hour IVM culture can acquire full competence in vitro, as
      illustrated by their development into healthy offspring. Endometrial quality
      appears to be a crucial determinant of pregnancy after nonhCG-triggered IVM.

PMID- 22365340
TI  - Effects of laser polar-body biopsy on embryo quality.
AB  - OBJECTIVE: To evaluate the effect of laser polar-body biopsy (PBB) for
      preimplantation genetic diagnosis on embryo quality. STUDY DESIGN: Retrospective
      case-control analysis. The quality of 145 embryos after PBB was compared to 276
      embryos of the same group of women without biopsy. SETTING: University-based
      tertiary-care medical center. PATIENT(S): Women with inherited genetics disease.
      INTERVENTION(S): Laser PBB of IVF embryos for genetic diagnosis. MAIN OUTCOME
      MEASURE(S): The study and control embryos were compared for fertilization rate,
      pronuclear grading, and cleavage-stage parameters on days 1, 2, and 3 after
      oocyte retrieval. RESULT(S): The study embryos demonstrated higher rates of
      cleavage arrest (3.6% vs. 0.7%), higher rate of significant fragmentation on day
      2 (9.5% vs. 3.0%), and lower rate of good cleavage embryos on day 2 (69.1% vs.
      78.4%) compared with control embryos. On day 3, the study embryos had lower
      cleavage rates (six or more blastomeres; 56.5% vs. 74.5%), higher fragmentation
      (11.7% vs. 3.9%), higher rate of embryos presenting inferior cleavage pattern
      (57.2% vs. 38.5%), and lower mean blastomere number (5.8 +/- 2.1 vs. 6.6 +/- 1.9)
      compared with control embryos. CONCLUSION(S): Polar-body biopsy may have a
      negative effect on embryo quality.

PMID- 22365341
TI  - [Internal medicine and Third Reich: a past that does not pass].

PMID- 22365342
TI  - Deep thrombocytopenia due to dengue fever in a patient splenectomized for immune
      thrombocytopenia.

PMID- 22365343
TI  - [Which treatments for infantile colics?].
AB  - BACKGROUND: Infantile colics or excessive crying represent a source of stress for
      parents and a frequent reason for encounter in primary care. OBJECTIVE: To assess
      the effectiveness of treatments of this syndrome from a systematic review.
      INFORMATION SOURCES: Medline, Cochrane and Embase databases. SELECTION OF
      STUDIES: We used the following inclusion criteria: therapeutic assessment of
      infant colics or excessive crying, randomized controlled trials or meta-analyses,
      published in English or French language. Thirty-one randomized controlled trials
      and one meta-analysis have been included. RESULTS: Allopathic drugs have not
      proved effectiveness (simethicone, lactase) and some of them can cause
      potentially serious adverse reactions (dicyclomine). Protein hydrolysate or soy
      formulas seem to be effective, but soy milk can induce allergies. Sucrose
      solutions provide some benefit in studies with low level of evidence.
      Effectiveness is likely for a probiotics (Lactobacillus reuteri) and for herbal
      mixtures containing fennel extracts. Evidence is lacking for manual (osteopathy,
      acupuncture) and behavioural therapies (decreased stimulations, reassurance of
      parents). LIMITATIONS: The definition of infantile colics and the methods used
      for crying measurement changed across trials. The included trials were of
      variable quality, especially with no double-blind procedure in 17 trials.
      CONCLUSION: The most validated treatments for infantile colics are the
      substitution of cows' milk by a hydrolysed formula, the use of L. reuteri and of
      fennel extracts.

PMID- 22365344
TI  - [Safety of tonka bean].

PMID- 22365345
TI  - Studies on the pathogenesis and survival of different culture forms of Listeria
      monocytogenes to pulsed UV-light irradiation after exposure to mild-food
      processing stresses.
AB  - The effects of mild conventional food-processing conditions on Listeria
      monocytogenes survival to pulsed UV (PUV) irradiation and virulence-associated
      characteristics were investigated. Specifically, this study describes the
      inability of 10 strains representative of 3 different culture forms or
      morphotypes of L. monocytogenes to adapt to normally lethal levels of PUV
      irradiation after exposure to sub-lethal concentrations of salt (7.5% (w/v) NaCl
      for 1 h), acid (pH 5.5 for 1 h), heating (48  degrees C for 1 h) or PUV (UV dose
      0.08 MUJ/cm(2)). Findings showed that the order of increasing sensitivity of L.
      monocytogenes of non-adapted and stressed morphotypes to low pH (pH 3.5 for 5 h,
      adjusted with lactic), high salt (17.5% w/v NaCl for 5 h), heating (60  degrees C
      for 1 h) and PUV-irradiation (100 pulses at 7.2 J and 12.8 J, equivalent to UV
      doses of 2.7 and 8.4 MUJ/cm(2) respectively) was typical wild-type smooth (S/WT),
      atypical filamentous rough (FR) and atypical multiple-cell-chain (MCR) variants.
      Exposure of L. monocytogenes cells to sub-lethal acid, salt or heating conditions
      resulted in similar or increased susceptibility to PUV treatments. Only prior
      exposure to mild heat stressing significantly enhanced invasion of Caco-2 cells,
      whereas subjection of L. monocytogenes cells to combined sub-lethal salt, acid
      and heating conditions produced the greatest reduction in invasiveness.
      Implications of these findings are discussed. This constitutes the first study to
      show that pre-exposure to mild conventional food-processing stresses enhances
      sensitivity of different culture morphotypes of L. monocytogenes to PUV, which is
      growing in popularity as an alternative or complementary approach for
      decontamination in the food environment.

PMID- 22365346
TI  - Development of a multilocus variable number of tandem repeat typing method for
      Oenococcus oeni.
AB  - Oenococcus oeni is responsible for the malolactic fermentation of wine. Genomic
      diversity has already been established in this species. In addition, winemakers
      usually report varying starter culture efficiency. The monitoring of indigenous
      and selected strains is essential for understanding strain survival and
      implantation during the winemaking process. In this study, we report the
      development of the first typing scheme for O. oeni using multiple-locus variable
      number of tandem repeat analysis (VNTR). The discriminatory power of 14 out of 44
      tandem repeat loci in the genome of the PSU-1 strain was initially evaluated with
      a test collection of 18 genotypically distinct starter strains. Then five VNTR
      loci, which can be easily scored with the technology used here, were identified
      and used to genotype a collection of 236 strains, previously classified by
      restriction endonuclease analysis-pulsed-field gel electrophoresis (REA-PFGE) and
      multilocus sequence typing (MLST) into 136 REA-PFGE types or 110 MLST types. The
      discriminatory power of VNTR (as determined by Simpson's index of discrimination)
      was higher than that of the other two methods, with 201 VNTR types. The targeted
      VNTR markers were found to be stable and did not change for the clones of the
      same strain deposited in a collection at intervals of several years. Strains
      isolated from the different wine producing areas or the products were assigned to
      phylogenetic groups and were statistically linked with the VNTR profiles. Another
      interesting observation was that the loci were found in sequences homologous to
      regions encoding for membrane-anchored proteins.

PMID- 22365347
TI  - Assessment of tetracycline and erythromycin resistance transfer during sausage
      fermentation by culture-dependent and -independent methods.
AB  - The food chain is considered one of the main routes of antibiotic resistance
      diffusion between animal and human population. The resistance to antimicrobial
      agents among enterococci could be related to the efficient exchange of
      transferable genetic elements. In this study a sausage model was used to evaluate
      the persistence of antibiotic resistant enterococci during meat fermentation and
      to assess horizontal gene transfer among bacteria involved in meat fermentation.
      Enterococcus faecalis OG1rf harbouring either pCF10 or pAMbeta1 plasmid was used
      as donor strain. The analysis of population dynamics during fermentation
      confirmed that the human isolate E. faecalis OG1rf was able to colonize the meat
      ecosystem with similar growth kinetics to that of food origin enterococci and to
      transfer the mobile genetic elements coding for tetracycline and erythromycin
      resistances. Transconjugant strains were detected after only two days of
      fermentation and increased their numbers during ripening even in the absence of
      selective antibiotic pressure. By means of culture-dependent and -independent
      molecular techniques, transconjugant strains carrying both tetracycline and
      erythromycin resistance genes were identified in enterococci, pediococci,
      lactobacilli and staphylococci groups. Our results suggest that the sausage model
      provides a suitable environment for horizontal transfer of conjugative plasmids
      and antibiotic resistance genes among food microbiota.

PMID- 22365348
TI  - Effect of prebiotic carbohydrates on the growth and tolerance of Lactobacillus.
AB  - Resistance to gastrointestinal conditions is a requirement for bacteria to be
      considered probiotics. In this work, we tested the resistance of six different
      Lactobacillus strains and the effect of carbon source to four different
      gastrointestinal conditions: presence of alpha-amylase, pancreatin, bile extract
      and low pH. Novel galactooligosaccharides synthesized from lactulose (GOS-Lu) as
      well as commercial galactooligosaccharides synthesized from lactose (GOS-La) and
      lactulose were used as carbon sources and compared with glucose. In general, all
      strains grew in all carbon sources, although after 24 h of fermentation the
      population of all Lactobacillus strains was higher for both types of GOS than for
      glucose and lactulose. No differences were found among GOS-Lu and GOS-La. alpha
      amylase and pancreatin resistance was retained at all times for all strains.
      However, a dependence on carbon source and Lactobacillus strain was observed for
      bile extract and low pH resistance. High hydrophobicity was found for all strains
      with GOS-Lu when compared with other carbon sources. However, concentrations of
      lactic and acetic acids were higher in glucose and lactulose than GOS-Lu and GOS
      La. These results show that the resistance to gastrointestinal conditions and
      hydrophobicity is directly related with the carbon source and Lactobacillus
      strains. In this sense, the use of prebiotics as GOS and lactulose could be an
      excellent alternative to monosaccharides to support growth of probiotic
      Lactobacillus strains and improve their survival through the gastrointestinal
      tract.

PMID- 22365349
TI  - The contribution of sampling uncertainty to total measurement uncertainty in the
      enumeration of microorganisms in foods.
AB  - Random samples of each of several food products were obtained from defined lots
      during processing or from retail outlets. The foods included raw milk (sampled on
      farm and from a bulk-milk tanker), sprouted seeds, raw minced meat, frozen de
      shelled raw prawns, neck-flaps from raw chicken carcasses and ready-to-eat
      sandwiches. Duplicate sub-samples, generally of 100 g, were examined for aerobic
      colony counts; some were examined also for counts of presumptive
      Enterobacteriaceae and campylobacters. After log(10)-transformation, all sets of
      colony count data were evaluated for conformity with the normal distribution (ND)
      and analysed by standard ANOVA and a robust ANOVA to determine the relative
      contributions of the variance between and within samples to the overall variance.
      Sampling variance accounted for >50% of the reproducibility variance for the
      majority of foods examined; in many cases it exceeded 85%. We also used an
      iterative procedure of re-sampling without replacement to determine the effects
      of sample size (i.e. the number of samples) on the precision of the estimate of
      variance for one of the larger data sets. The variance of the repeatability and
      reproducibility variances depended on the number of replicate samples tested (n)
      in a manner that was characteristic of the underlying distribution. The results
      are discussed in relation to the use of measurement uncertainty in assessing
      compliance of results with microbiological criteria for foods.

PMID- 22365350
TI  - Occurrence and characterization of Listeria spp. in ready-to-eat retail foods
      from Vancouver, British Columbia.
AB  - The occurrence of Listeria spp. and Listeria monocytogenes in retail RTE meat and
      fish products in Vancouver, British Columbia (B.C.) was investigated. To assess
      potential consumer health risk, recovered L. monocytogenes isolates were
      subjected to genotypic and phenotypic characterization. Conventional methods were
      used to recover Listeria spp. from deli meat (n = 40) and fish (n = 40) samples
      collected from 17 stores. Listeria spp. were recovered only from fish samples
      (20%); 5% harboured Listeria innocua, 5% had L. monocytogenes and 10% contained
      Listeria welshimeri. L. monocytogenes isolates serotyped as 1/2a and 1/2b,
      possessed dissimilar PFGE patterns, and had full-length InlA. Three 1/2a clonal
      isolates encoded the 50 kb genomic island, LGI1. Antimicrobial resistance (AMR)
      profiling showed all Listeria spp. possessed resistance to cefoxitin and
      nalidixic acid. L. monocytogenes were resistant to clindamycin, two were
      resistant to streptomycin, and one to amikacin. Reduced susceptibility to
      ciprofloxacin was seen in all L. monocytogenes, L. innocua and three L.
      welshimeri isolates. Reduced susceptibility to amikacin and chloramphenicol was
      also observed in one L. monocytogenes and three L. welshimeri isolates,
      respectively. Recovery of L. monocytogenes in fish samples possessing AMR, full
      length InlA, LGI1, and serotypes frequently associated with listeriosis suggest
      B.C. consumers are exposed to high-risk strains.

PMID- 22365351
TI  - On-farm implementation of a starter culture for improved cocoa bean fermentation
      and its influence on the flavour of chocolates produced thereof.
AB  - Cocoa bean fermentations controlled by means of starter cultures were introduced
      on several farms in two different cocoa-producing regions (West Africa and
      Southeast Asia). Two starter culture mixtures were tested, namely one composed of
      Saccharomyces cerevisiae H5S5K23, Lactobacillus fermentum 222, and Acetobacter
      pasteurianus 386B (three heaps and one box), and another composed of L. fermentum
      222 and A. pasteurianus 386B (seven heaps and one box). In all starter culture
      added cocoa bean fermentation processes, the inoculated starter culture species
      were able to outgrow the natural contamination of the cocoa pulp-bean mass and
      they prevailed during cocoa bean fermentation. The application of both added
      starter cultures resulted in fermented dry cocoa beans that gave concomitant milk
      and dark chocolates with a reliable flavour, independent of cocoa-producing
      region or fermentation method. The addition of the lactic acid bacterium
      (LAB)/acetic acid bacterium (AAB) starter culture to the fermenting cocoa pulp
      bean mass accelerated the cocoa bean fermentation process regarding citric acid
      conversion and lactic acid production through carbohydrate fermentation. For the
      production of a standard bulk chocolate, the addition of a yeast/LAB/AAB starter
      culture was necessary. This enabled an enhanced and consistent ethanol production
      by yeasts for a successful starter culture-added cocoa bean fermentation process.
      This study showed possibilities for the use of starter cultures in cocoa bean
      fermentation processing to achieve a reliably improved fermentation of cocoa pulp
      bean mass that can consistently produce high-quality fermented dry cocoa beans
      and flavourful chocolates produced thereof.

PMID- 22365352
TI  - Inactivation of Salmonella spp. in liquid whole egg using pulsed electric fields,
      heat, and additives.
AB  - This paper evaluates the lethal effectiveness on 7 different Salmonella serovars
      of the application, in static and continuous conditions, of pulsed electric
      fields (PEF) followed by heat treatments in liquid whole egg (LWE) with additives
      (EDTA or triethyl citrate-TC-). Compared to heat treatments, the PEF (25 kV/cm
      and 75-100 kJ/kg) followed by heat (52 degrees C/3.5', 55 degrees C/2', or 60
      degrees C/1') in LWE with 2% TC permitted the reduction of heat treatment time
      from 92 fold at 52 degrees C to 3.4 fold at 60 degrees C, and 4.8 fold at 52
      degrees C in LWE with EDTA for a 9-Log(10) reduction of the population of
      Salmonella Enteritidis. The new designed treatments inactivated more than 5
      Log(10) cycles of Salmonella serovars Dublin, Enteritidis 4300, Enteritidis 4396,
      Typhimurium, Typhi, Senftenberg, and Virchow, both in static and continuous
      conditions. Conversely, current heat pasteurization treatments of 60 degrees
      C/3.5' and 64 degrees C/2.5' reduced 5 Log(10) cycles of various serovars of
      Salmonella but only 2 and 3-4 Log(10) cycles of Salmonella Senftenberg and
      Salmonella Enteritidis 4396, respectively. Soluble protein content (SPC)
      decreased 1.8%, 1.3%, and 5.0% after the successive application of PEF followed
      by heat at 52, 55, and 60 degrees C in the presence of 2% TC, respectively,
      whereas 1.6% and 9.4% of SPC were reduced after heat pasteurization at 60 and 64
      degrees C, respectively. Results indicate that designed treatments could be an
      alternative to current heat pasteurization of LWE as showed higher lethal
      effectiveness against Salmonella serovars with a similar or even lower decrement
      of the soluble protein content.

PMID- 22365353
TI  - Use of deodorized yellow mustard powder to control Escherichia coli O157:H7 in
      dry cured Westphalian ham.
AB  - Dry cured (uncooked) hams with low water activity and pH >=5.6 seem a likely food
      vehicle for Escherichia coli O157:H7. In previous work, isothiocyanates produced
      from mustard glucosinolates by bacterial myrosinase-like activity converted
      deodorized mustard into a potent antimicrobial in dry sausage. In this study its
      value in controlling E. coli O157:H7 survival in Westphalian ham was
      investigated. Hams were inoculated with a 7.5 log cfu g(-1) cocktail of E. coli
      O157:H7, 4% or 6% (w/w) deodorized yellow mustard powder was surface applied and
      monitored 80 d for pathogen survival. In one trial to accelerate formation of
      isothiocyanate, a Staphylococcus (S.) carnosus meat starter culture was added to
      hams at 45 d (after salt equilibration). At 21 d, E. coli O157:H7 was reduced by
      3 log cfu g(-1) on hams treated with mustard powder compared to only a 1 log cfu
      g(-1) reduction in the control. By 45 d, mustard powder caused a reduction of >5
      log cfu g(-1)E. coli O157:H7, whereas it took 80 d for numbers in control hams to
      be similarly reduced. Although the commercial process used caused a 5 log cfu g(
      1) reduction of E. coli O157:H7 in 80 d, 4% or 6% deodorized mustard accelerated
      this reduction and the S. carnosus starter culture may have contributed to the
      maintenance of this effect.

PMID- 22365354
TI  - Microbiological spoilage of vacuum and modified atmosphere packaged Vietnamese
      Pangasius hypophthalmus fillets.
AB  - This study investigated the identity, growth and metabolite production of micro
      organisms causing spoilage of Pangasius hypophthalmus fillets packaged in air,
      vacuum and modified atmospheres (MAP) (MAP 1: 50%CO(2)-50%N(2) and MAP 2:
      50%CO(2)-50%O(2)) during storage at 4  degrees C. Based on the time it took for
      psychrotrophic total colony counts to exceed 7 log cfu g(-1), the shelf life of
      the fillets packaged in air, vacuum, MAP 1 and MAP 2 was estimated to be 7, 10,
      12 and 14 days respectively. The longest lag phases were observed in the samples
      packaged in MAP 2 (50%CO(2)-50%O(2)). In the fillets packaged in air and under
      vacuum, the dominant flora identified by partial 16S rDNA sequencing at the end
      of the shelf life generally consisted of Gram-negative bacteria mostly belonging
      to the genera Serratia and Pseudomonas. In contrast, lactic acid bacteria
      (Carnobacterium maltaromaticum and Carnobacterium divergens) and Brochothrix
      thermosphacta were identified as the dominant spoilage flora in the samples
      packaged under the two MAPs investigated. By means of solid-phase microextraction
      gas chromatography mass spectrometry (SPME GC-MS) analysis, volatile organic
      compounds in the headspace of the samples at the end of the shelf life were
      identified for each packaging condition. Based on these results, a selective ion
      flow tube mass spectrometry (SIFT-MS) method was developed to quantify the
      production of volatile metabolites during storage of the fillets. The results of
      these analyses indicated that several compounds contributed to the bacterial
      spoilage of Pangasius fillets e.g., ethanol, 2,3-butanediol, diacetyl, acetoin,
      ethyl acetate, acetic acid and sulfur compounds. It also emerged that the
      production of these compounds was dependent on the packaging condition applied.

PMID- 22365355
TI  - Detection of human norovirus in cherry tomatoes, blueberries and vegetable salad
      by using a receptor-binding capture and magnetic sequestration (RBCMS) method.
AB  - In this study, we developed a sensitive receptor-binding capture and magnetic
      sequestration (RBCMS) method capable of concentrating human norovirus (HuNoV)
      from various food samples within few hours. We found that distilled water was
      suitable for the elution of HuNoV from inoculated tomatoes and blueberries, and
      glycine buffer improved the elution of HuNoV from inoculated salad. A significant
      improvement in post-extraction RNA yield was achieved by sequentially heat
      releasing and column-extracting over either technique alone. The viral recovery
      of the RBCMS method was significantly higher than both the same-day PEG method
      (90 min PEG precipitation) and the two-day PEG method (overnight PEG
      precipitation) with a recovery rate of 8.75%, 1.03% and 5.40%, respectively. The
      detection limit of HuNoV by RBCMS method was significantly improved to 0.056 RTU.
      The estimated minimal concentration powers (MCPs) were 6.11, 30.48, and 63.60
      fold for the same-day PEG, two-day PEG, and RBCMS methods, respectively. RNase
      protection assay suggests that the viral genome was protected from RNase attack
      by remaining within the viral capsid. The signal detected by the RBCMS method
      might be more biologically relevant, as it requires both intact viral capsid to
      bind to HBGA receptors and the presence of viral genome to be amplified. Overall,
      the RBCMS method takes significantly less time than current PEG precipitation
      methods, recovers a higher yield of HuNoV from various food samples, and hence
      exhibits higher sensitivity.

PMID- 22365356
TI  - Thermal inactivation of Escherichia coli O157:H7 and Salmonella on catfish and
      tilapia.
AB  - Thermal inactivation kinetics of individual cocktails of Escherichia coli
      O157:H7, or of Salmonella meat isolates or seafood isolates were determined in
      catfish and tilapia. Determinations were done at 55, 60 and 65  degrees C using a
      circulating-water bath and calculated using linear regression analysis.
      Salmonella seafood and meat isolates D-10 values on the finfish were the same and
      ranged from 425 to 450, 27.1 to 51.4, 2.04-3.8 s (z = 4.3  degrees C) at 55, 60
      and 65  degrees C, respectively. The E. coli O157:H7 D-10 values ranged from 422
      to 564, 45.2 to 55.5 and 3.3-4.2 s (z = 4.3  degrees C) at 55, 60 and 65 degrees 
      C, respectively. The only statistical difference (P <= 0.05) was found when
      comparing the D-10 values for E. coli O157:H7 at 55  degrees C on catfish and
      tilapia. The other D-10 values for the Salmonella at all temperatures and E. coli
      O157:H7 at 60 and 65  degrees C on the catfish or tilapia showed no statistical
      difference. D-10 values for the catfish and tilapia were significantly lower than
      the reported values in other food systems, but the z-values were within the
      literature reported range. These D-10 values can be used to determine cooking
      parameters of finfish.

PMID- 22365358
TI  - Characterization of the "viable but nonculturable" (VBNC) state in the wine
      spoilage yeast Brettanomyces.
AB  - Although the viable but not culturable (VBNC) state has been studied in detail in
      bacteria, it has been suggested that maintenance of viability with loss of
      culturability also exists in eukaryotic cells, such as in the wine spoilage yeast
      Brettanomyces. To provide conclusive evidence for the existence of a VBNC state
      in this yeast, we investigated its capacity to become viable and nonculturable
      after sulfite stress, and its ability to recover culturability after stressor
      removal. Sulfite addition induced loss of culturability but maintenance of
      viability. Increasing the medium pH to decrease the concentration of toxic SO(2)
      allowed yeast cells to become culturable again, thus demonstrating the occurrence
      of a VBNC state in Brettanomyces upon SO(2) exposure. Relative to culturable
      Brettanomyces, VBNC yeast cells were found to display a 22% decrease in size on
      the basis of laser granulometry. Assays for 4-ethylguaiacol and 4-ethylphenol,
      volatile phenols produced by Brettanomyces, indicated that spoilage compound
      production could persist in VBNC cells. These morphological and physiological
      changes in VBNC Brettanomyces were coupled to extensive protein pattern
      modifications, as inferred by comparative two-dimensional electrophoresis and
      mass spectrometric analyses. Upon identification of 53 proteins out of the 168
      spots whose abundance was significantly modified in treated cells relative to
      control, we propose that the SO(2)-induced VBNC state in Brettanomyces is
      characterized by a reduced glycolytic flux coupled to changes in redox
      homeostatis/protein turnover-related processes. This study points out the
      existence of common mechanisms between yeast and bacteria upon entry to the VBNC
      state.

PMID- 22365357
TI  - Rapid discrimination of Bifidobacterium animalis subspecies by matrix-assisted
      laser desorption ionization-time of flight mass spectrometry.
AB  - Currently, the species Bifidobacterium animalis consists of two subspecies, B.
      animalis subsp. lactis and B. animalis subsp. animalis. Among these two
      subspecies, B. animalis subsp. lactis is especially important because it is
      widely used in the manufacture of probiotic dairy products. The application of
      these microbes in the food industry demands fast, accurate and low cost methods
      to differentiate between species and strains. Although various genotypic methods
      have been employed to discriminate between these two subspecies, they are not
      easily adapted for rapid identification in the industry. The purpose of this
      study was to evaluate the use of matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF MS) to differentiate between the two
      subspecies of B. animalis, and for discrimination at strain level. We identified
      twenty-three strains of B. animalis at subspecies and strain level by genotypic
      methods and by proteomics using MALDI-TOF MS. The proteomics identification by
      MALDI-TOF was nearly identical to that obtained by genotypic identification using
      comparison of tuf and atpD gene sequences, and single-nucleotide polymorphisms
      (SNPs), insertions, and deletions (INDELs). We identified four protein markers,
      L1, L2, A1, and A2, which are useful for discriminating between both subspecies.
      Proteomics identification using MALDI-TOF MS was therefore an accurate method for
      discriminating and identifying these bacteria. Given the speed in which this
      method is achieved (~20 min including sample preparation), MALDI-TOF MS is
      promising as a tool for rapid discrimination of starter cultures and probiotics.

PMID- 22365359
TI  - Influence of lactate and acetate salt adaptation on Salmonella Typhimurium acid
      and heat resistance.
AB  - The aim of the present study was to determine the survival of Salmonella
      Typhimurium adapted with sodium lactate (NaL), potassium lactate/sodium acetate
      mixture (KL/NaA) or sodium acetate (NaA) in simulated gastric fluid (SGF) and
      during heat treatment. NaL-, KL/NaA- and NaA-adapted cells were prepared by
      incubating in tryptic soy broth (TSB) containing these salts at 5, 5 and 3% (w/v)
      concentration levels, respectively, for 24 h at 37  degrees C. The Baranyi model
      was used to compare the growth kinetic parameters of adapted cells. The acid and
      heat resistance of adapted cells were determined by incubating in SGF (pH 2.04)
      at 37  degrees C and in TSB at 55.8, 57.8 and 59.8  degrees C, respectively.
      Adapted cells had significantly (P < 0.05) longer lag phase duration (LPD) and
      slower maximum growth rate (MGR) than non-adapted cells. The acid resistance of
      KL/NaA-adapted cells was not significantly (P > 0.05) different from that of non
      adapted cells. NaL-adapted cells were more susceptible to the low pH environment,
      whereas NaA-adapted cells showed enhanced acid resistance compared to non-adapted
      and other adapted cells. Unlike acid resistance, both NaL- and NaA-adapted cells
      showed enhanced heat resistance with increased D-values, regardless of treatment
      temperatures. Thus, this study indicates that adaptation of S. Typhimurium to 5%
      NaL or 3% NaA could enhance their ability to survive thermal processes or in the
      human stomach, possibly increasing the risk of Salmonella outbreaks.

PMID- 22365360
TI  - Transfer of Salmonella Enteritidis to four types of surfaces after cleaning
      procedures and cross-contamination to tomatoes.
AB  - The objectives of the present study were to evaluate the spread of Salmonella
      Enteritidis to different cutting boards (wood, triclosan-treated plastic, glass,
      and stainless steel) from contaminated poultry skin (5 log CFU/g) and then to
      tomatoes and to analyze the effect of different protocols used to clean these
      surfaces to control contamination. The following procedures were simulated: (1)
      no cleaning after handling contaminated poultry skin; (2) rinsing in running
      water; (3) cleaning with dish soap and mechanical scrubbing; and (4) cleaning
      with dish soap and mechanical scrubbing, followed by disinfection with
      hypochlorite. The pathogen was recovered from all surfaces following procedure 1,
      with counts ranging from 1.90 to 2.80 log, as well as from the tomatoes handled
      on it. Reduced numbers of S. Enteritidis were recovered using the other
      procedures, both from the surfaces and from the tomatoes. Counts were
      undetectable after procedure 4. From all surfaces evaluated, wood was the most
      difficult to clean, and stainless steel was the easiest. The use of hypochlorite
      as a disinfecting agent helped to reduce cross-contamination.

PMID- 22365361
TI  - Heat acclimation and the role of RpoS in prolonged heat shock of Escherichia coli
      O157.
AB  - Escherichia coli, a commensal mesophile that primarily inhabits the gastro
      intestinal tract, responds to temperature up-shifts with transient expression of
      stress-response proteins. The goal of this study was to identify adaptive
      proteins of E. coli O157 crucial for growth resumption of this human pathogen
      after heat shock, with specific focus on the role of the RpoS sigma factor. Using
      the comparative proteomic analysis of hyper-thermally acclimatized wild-type
      strain B-1 and rpoS-mutant strain SV521, we identified 39 proteins that underwent
      significantly-different induction upon temperature shock at 45 degrees C or rpoS
      mutation. All identified proteins of the heat post-acclimation stimulon fell into
      two large sub-groups: (i) stress proteins, including molecular chaperons,
      proteases, DNA/RNA stabilizing enzymes, and anti-oxidant proteins, and (ii)
      housekeeping proteins. It was found that in the heat stress stimulon RpoS has
      significantly (P=0.012) limited control over the key stress proteins involved in
      translation, translational elongation, protein folding and refolding. However,
      RpoS showed a significant (P=0.035) control over the cellular metabolic processes
      that included NADPH regeneration, pentose-phosphate shunt, nicotinamide
      nucleotide and NADP metabolic processes, reflecting its specific importance in
      promoting resource utilization (energy, protein synthesis etc.) during
      proliferation of hyperthermally-adapted cells. Pathogenic strains, like E. coli
      O157, have the ability to survive a variety of harsh stress conditions, leading
      to their entry into the food chain, and subsequent pathogenesis. This research
      offers insights into the physiological response of this pathogen during the
      critical period following adaptation to thermal stress and subsequent resumption
      of growth.

PMID- 22365362
TI  - A quantum dot-based optical immunosensor for human serum albumin detection.
AB  - In this study, a CdSe/ZnS quantum dot (QD)-based immunosensor using a simple
      optical system for human serum albumin (HSA) detection is developed. Monoclonal
      anti-HSA (AHSA) immobilized on 3-aminopropyltriethoxysilane (APTES)-modified
      glass was used to capture HSA specifically. Bovine serum albumin (BSA) was used
      to block non-specific sites. The solution, containing AHSA-QD complex prepared by
      mixing biotinylated polyclonal anti-HSA and streptavidin coated QD, was used to
      conjugate with the HSA molecules captured on AHSA/BSA/APTES-modified glass for
      the modification of HSA with QD. A simple optical system, comprising a diode
      laser (405 nm), an optical lens, a 515-nm-long pass filter, and an Si-photodiode,
      was used to detect fluorescence and convert it to photocurrent. The current
      intensity was determined by the amount of QD specifically conjugated with HSA,
      and was therefore HSA-concentration-dependent and could be used to quantify HSA
      concentration. The detection limit of the pure QD solution was ~3.5*10(-12) M,
      and the detection limit for the CdSe/ZnS QD-based immunosensor developed in this
      study was approximately 3.2*10(-5) mg/ml. This small optical biosensing system
      shows considerable potential for future applications of on-chip liver-function
      detection.

PMID- 22365363
TI  - Impedimetric detection of single-stranded PCR products derived from methicillin
      resistant Staphylococcus aureus (MRSA) isolates.
AB  - Using electrochemical impedance spectroscopy (EIS) the sensitive and specific
      detection of the antibiotic resistance gene mecA has been demonstrated. The gene
      sequence was obtained from clinical Staphylococcus aureus isolates. Initially a
      mecA specific probe was selected from hybridisation tests with a 3' and 5'
      version of a previously published probe sequence. When immobilised on a gold
      electrode in PNA form it was possible to detect hybridisation of mecA PCR product
      electrochemically at concentrations as low as 10nM. By incorporating an undecane
      thiol and 1.8 nm glycol spacer into the PNA probe it was possible to extend the
      limit of detection for mecA to 10 pM. Most published studies on EIS and nucleic
      acid detection report the use of short artificial DNA sequences or novel signal
      amplification schemes which improve sensitivity whereas this study reports the
      successful detection of long DNA fragments produced by PCR following extraction
      from clinical isolates. Finally, using screen printed electrodes the paper
      demonstrates hybridisation monitoring of mecA in an "on-line" assay format under
      ambient conditions which paves the way for rapid mecA detection in point of care
      scenarios.

PMID- 22365364
TI  - Oligonucleotide-functionalized silver nanoparticle extraction and laser-induced
      fluorescence for ultrasensitive detection of mercury(II) ion.
AB  - This study describes the development of a simple, sensitive, and selective
      detection system for Hg(2+) ion by combining nanoparticle extraction, fluorescent
      dye labeling, and flow injection analysis (FIA) detection. Repeats of 33 thymine
      nucleotides-functionalized silver nanoparticles (T(33)-AgNPs) specifically
      capture Hg(2+) from aqueous solution through the coordination between T(33) and
      Hg(2+). Meanwhile, Hg(2+) ion drives a T(33) conformational change from a random
      coil to a folded structure. The T(33)-Hg(2+)complexes adsorbed on the NP surface
      were collected from the initial sample by centrifugation, and they were then
      detached from the NP surface by addition of H(2)O(2). The T(33)-Hg(2+) complexes
      preferentially bind to SYBR Green I (SG), enhancing the SG fluorescence. By
      contrast, SG fluoresces only weakly in the presence of T(33) alone. The
      extraction efficiency of Hg(2+) was highly dependent on polythymine length, the
      concentration of T(33)-AgNPs, and the incubaton time of T(33)-AgNPs with Hg(2+).
      Under optimal extraction and labeling conditions, FIA detection showed the limit
      of detection (at a signal-to-noise ratio of three) for Hg(2+)of 3 pM. The
      selectivity of our analytical system is more than 1000-fold for Hg(2+) over any
      metal ions. We validated the applicability of this system for the determination
      of Hg(2+) concentrations in tap water.

PMID- 22365365
TI  - Fabrication of polymeric electron-transfer mediator/enzyme hydrogel multilayer on
      an Au electrode in a layer-by-layer process.
AB  - The layer-by-layer (LBL) construction of an enzyme electrode covered with a
      multilayer structure alternately composed of a polymeric electron transfer
      mediator and a polymer-modified enzyme was examined. Poly(2-methacryloyloxyethyl
      phosphorylcholine-co-p-vinylphenylboronic acid-co-vinylferrocene) (PMVF) was
      synthesized and used as a polymeric electron transfer mediator. Glucose oxidase
      (GOx) was selected as a model enzyme and poly(vinyl alcohol) (PVA) chains were
      bound to the GOx (GOx-PVA) under mild conditions. The PMVF and PVA formed a gel
      spontaneously through a selective reaction between phenylboronic acid units and
      hydroxyl groups in both polymers. Using the spin coating technique, a repeating
      PMVF/GOx-PVA multilayer was fabricated on the surface of an Au electrode. The
      thickness of each PMVF/GOx-PVA layer was around 5.8 nm, corresponding to the
      dimensions of GOx. The electrochemical performance of the electrode was evaluated
      in glucose concentration measurement. The oxidation current of glucose by GOx was
      measured at 0.38 V (vs. Ag/AgCl), verifying that ferrocene units in the PMVF of
      the hydrogel electrically wired the immobilized GOx. Moreover, the current
      increased with the number of PMVF/GOx-PVA layers. That is, both intermolecular
      electron transfer between each individual layer and the presence of a freely
      diffusing substrate in the hydrogel were achieved. We conclude that a LBL
      structure constructed from PMVF and a PVA-modified enzyme is effective for use in
      developing bioelectronic devices that employ enzyme molecules.

PMID- 22365366
TI  - First case of human infection with a Bunyamwera serogroup virus in Argentina.

PMID- 22365367
TI  - Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg
      seroconversion in a subgroup of patients with chronic hepatitis B.
AB  - BACKGROUND: Nucleos(t)ides effectively halt disease progression in hepatitis B
      but require long-term medication. OBJECTIVES: To determine whether add-on of peg
      IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces
      seroconversion. STUDY DESIGN: We observed HBsAg kinetics in 12 patients on a
      stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN
      alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean
      baseline HBsAg was 4695 (range 16-15,120)IU/ml. RESULTS: A continuous decline of
      HBsAg was observed in 2 patients. The slope, respectively, became detectable at
      week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48,
      and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3
      fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus
      tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the
      patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative,
      genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving
      entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the
      remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01
      0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No
      unexpected side effects were observed. DISCUSSION: We observed that the add-on of
      peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may
      have been higher with prolongation of therapy. The add-on concept merits to be
      evaluated in a clinical trial.

PMID- 22365368
TI  - A novel hybrid nano zerovalent iron initiated oxidation--biological degradation
      approach for remediation of recalcitrant waste metalworking fluids.
AB  - Disposal of operationally exhausted metal working fluids (MWF) through a
      biological route is an attractive option, since it is effective with relatively
      low energy demands. However, it is enormously challenging since these fluids are
      chemically complex, including the addition of toxic biocides which are added
      specifically to retard bio-deterioration whilst the fluids are operational. Nano
      sized elemental iron represents a new generation of environmental remediation
      technologies. Laboratory scale batch studies were performed to test the
      degradation ability of a semi-synthetic metalworking fluid (MWF) wastewater
      (which was found to be resistant to initial bacterial treatment in specifically
      established bioreactors) by employing a novel hybrid approach. The approach was
      to combine the synergistic effects of nano zerovalent iron (nZVI) induced
      oxidation, followed by biodegradation, specifically for the remediation of
      recalcitrant components of MWF effluent. Addition of nZVI particles to oxygenated
      wastewater resulted in oxidation of organic contaminants present. Our studies
      confirmed 78% reduction in chemical oxygen demand (COD) by nZVI oxidation at pH
      3.0 and 67% reduction in neutral pH (7.5), and 85% concurrent reduction in
      toxicity. Importantly, this low toxicity made the nZVI treated effluent more
      amenable for a second stage biological oxidation step. An overall COD reduction
      of 95.5% was achieved by the novel combined treatment described, demonstrating
      that nZVI oxidation can be exploited for enhancing the biodegradability of a
      recalcitrant wastewater in treatment processes.

PMID- 22365369
TI  - Ozonation products of triclosan in advanced wastewater treatment.
AB  - Triclosan is an antimicrobial agent widely used in many household and personal
      care products. Widespread use of this compound has led to the elevated
      concentrations of triclosan in wastewater, wastewater treatment plants and
      receiving waters. In this study removal of triclosan by aqueous ozone was
      investigated and the degradation products formed during ozonation of an aqueous
      solution of triclosan were analyzed by GC-MS and HPLC-MS/MS. The following
      transformation products have been identified: 2,4-dichlorophenol, chloro-catecol,
      mono-hydroxy-triclosan and di-hydroxy-triclosan during treatment process.
      Cytotoxicity and genotoxicity of pure triclosan and 2,4-dichlorophenol have been
      investigated and the results showed reduced genotoxic effects after ozonation,
      though the respective chlorophenol is harmful to aquatic organisms.

PMID- 22365370
TI  - Spatial and temporal variation in indicator microbe sampling is influential in
      beach management decisions.
AB  - Fecal indicator microbes, such as enterococci, are often used to assess potential
      health risks caused by pathogens at recreational beaches. Microbe levels often
      vary based on collection time and sampling location. The primary goal of this
      study was to assess how spatial and temporal variations in sample collection,
      which are driven by environmental parameters, impact enterococci measurements and
      beach management decisions. A secondary goal was to assess whether enterococci
      levels can be predictive of the presence of Staphylococcus aureus, a skin
      pathogen. Over a ten-day period, hydrometeorologic data, hydrodynamic data,
      bather densities, enterococci levels, and S. aureus levels including methicillin
      resistant S. aureus (MRSA) were measured in both water and sand. Samples were
      collected hourly for both water and sediment at knee-depth, and every 6 h for
      water at waist-depth, supratidal sand, intertidal sand, and waterline sand.
      Results showed that solar radiation, tides, and rainfall events were major
      environmental factors that impacted enterococci levels. S. aureus levels were
      associated with bathing load, but did not correlate with enterococci levels or
      any other measured parameters. The results imply that frequencies of advisories
      depend heavily upon sample collection policies due to spatial and temporal
      variation of enterococci levels in response to environmental parameters. Thus,
      sampling at different times of the day and at different depths can significantly
      impact beach management decisions. Additionally, the lack of correlation between
      S. aureus and enterococci suggests that use of fecal indicators may not
      accurately assess risk for some pathogens.

PMID- 22365371
TI  - Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for
      chronic kidney disease patients.
AB  - Chronic kidney disease (CKD) is increasingly common, and there is an increasing
      awareness that every strategy should be used to avoid complications of CKD.
      Restriction of dietary protein intake has been a relevant part of the management
      of CKD for more than 100 years, but even today, the principal goal of protein
      restricted regimens is to decrease the accumulation of nitrogen waste products,
      hydrogen ions, phosphates, and inorganic ions while maintaining an adequate
      nutritional status to avoid secondary problems such as metabolic acidosis, bone
      disease, and insulin resistance, as well as proteinuria and deterioration of
      renal function. This supplement focuses on recent experimental and clinical
      findings related to an optimized dietary management of predialysis, dialysis, and
      transplanted patients as an important aspect of patient care. Nutritional
      treatment strategies are linked toward ameliorating metabolic and endocrine
      disturbances, improving/maintaining nutritional status, as well as delaying the
      renal replacement initiation and improving outcomes in CKD patients. A final
      consensus states that dietary manipulations should be considered as one of the
      main approaches in the management program of CKD patients and that a reasonable
      number of patients with moderate or severe CKD benefit from dietary
      protein/phosphorus restriction.

PMID- 22365372
TI  - Keto acid therapy in predialysis chronic kidney disease patients: final
      consensus.

PMID- 22365374
TI  - Algal wastewater treatment systems for seasonal climates: application of a simple
      modelling approach to generate local and regional design guidelines.
AB  - Algal waste stabilisation ponds (WSP) provide a means of treating wastewater, and
      also a potential source of water for re-use in irrigation, aquaculture or algal
      biomass cultivation. The quantities of treated water available and the periods in
      which it is suitable for use or discharge are closely linked to climatic factors.
      This paper describes the application, at a continent-wide scale, of a modelling
      approach based on the use of readily available climate datasets to provide WSP
      design and performance guidelines linked to geographical location. Output is
      presented in regionally-based contour maps covering a wide area of Russia and
      central Asia and indicating pond area, earliest discharge date, discharge
      duration, wastewater inflow:outflow ratio and salinity under user-specified
      conditions. The results confirm that broad-brush discharge guidelines of the type
      commonly used in North America can safely be applied; but suggest that a more
      detailed approach is worthwhile to optimise operating regimes for local
      conditions. The use of long-series climate data can also permit tailoring of
      designs to specific sites. The work considers a simple 2-pond system, but other
      configurations and operating regimes should be investigated, especially for the
      wide range of locations across the world that are intermediate between the 'one
      short discharge per year' mode and year-round steady-state operation.

PMID- 22365373
TI  - Effect of transtympanic low-pressure therapy in patients with unilateral
      Meniere's disease unresponsive to betahistine: a randomised, placebo-controlled,
      double-blinded, clinical trial.
AB  - OBJECTIVE: To determine the effect of the Meniett low-pressure generator on the
      subjective symptoms and audiovestibular disease markers of patients with
      unilateral Meniere's disease unresponsive to betahistine treatment. METHODS:
      Randomised, placebo-controlled, double-blinded, clinical trial at a tertiary
      referral centre. After ventilation tube placement, patients were randomised to
      the active treatment or placebo group. Monitoring comprised audiometry and air
      caloric testing and a vertigo diary (enabling calculation of vertigo and activity
      scores, and the number of vertigo days, vertigo-free days and sick days).
      RESULTS: Sixty-eight patients completed the study. For the active treatment
      versus placebo group, the following pre- and post-treatment values, and
      significances for treatment effect comparisons, were respectively seen:
      cumulative vertigo scores, 22.47 and 15.97 vs 20.42 and 19.23 (p = 0.048);
      vertigo days, 6.5 and 4.08 vs 5.94 and 5.52 (p = 0.102); sick days, 3.08 and 0.78
      vs 2.87 and 3.45 (p = 0.041); vertigo-free days, 14.47 and 17.61 vs 15.48 and
      17.58 (p = 0.362); activity score, 23.61 and 13.42 vs 24.68 and 20.23 (p =
      0.078); low-tone hearing threshold, 49.15 and 53.18 dB nHL vs 41.66 and 46.10 dB
      nHL (p > 0.05); and slow phase velocity in response to caloric stimulation, 18.86
      and 18.72  degrees /second vs 14.97 and 15.95  degrees /second, (p > 0.05).
      CONCLUSION: Use of the Meniett low-pressure generator improved patients' vertigo
      but not their hearing or vestibular function. This safe, minimally invasive
      treatment is recommended as second-line treatment for unilateral Meniere's
      disease.

PMID- 22365376
TI  - Management of foreign bodies in the airway and oesophagus.
AB  - BACKGROUND: Ingestion and/or aspiration of foreign bodies (FB) are avoidable
      incidents. Children between 1 and 3 years are common victims for many reasons:
      exploration of the environment through the mouth, lack of molars which decreases
      their ability to properly chew food, lack of cognitive capacity to distinguish
      between edible and inedible objects, and tendency to distraction and to perform
      other activities, like playing, whilst eating. Most FBs are expelled
      spontaneously, but a significant percentage impacts the upper aerodigestive
      tract. Approximately 80% of children's choking episodes are evaluated by
      pediatricians. The symptoms of aspiration or ingestion of FBs can simulate
      different paediatric diseases such as asthma, croup or pneumonia, delaying the
      correct diagnosis. SYMPTOMS: There are three clinical phases both in aspiration
      and in ingestion of FBs: initial stage (first stage or impaction or FB) shows
      choking, gagging and paroxysms of coughing, obstruction of the airway (AW),
      occurring at the time of aspiration or ingestion. These signs calm down when the
      FB lodges and the reflexes grow weary (second stage or asymptomatic phase).
      Complications occur in the third stage (also defined as complications' phase),
      when the obstruction, erosion or infection cause pneumonia, atelectasis, abscess
      or fever (FB in AW), or dysphagia, mediastinum abscess, perforation or erosion
      and oesophagus (FB in the oesophagus). The first symptoms to receive medical care
      may actually represent a complication of impaction of FB. LOCATIONS AND
      MANAGEMENT: Determining the site of obstruction is important in managing the
      problem. The location of the FB depends on its characteristics and also on the
      position of the person at the time of aspiration. Determining the site of
      obstruction is important in managing the problem. Larynx and trachea have the
      lowest prevalence, except in children under 1year. They are linked with the most
      dangerous outcomes, complete obstruction or rupture. Bronchus is the preferred
      location in 80-90% of AW's cases. Esophageal FBs are twice more common than
      bronchial FBs, although most of these migrate to the stomach and do not require
      endoscopic removal. Diagnosis of FB proceeds following the traditional steps,
      with a particular stress on history and radiological findings as goal standards
      for the FB retrieval. The treatment of choice for AW's and esophageal FBs is
      endoscopic removal. Endoscopy should be carried out whenever the trained
      personnel are available, the instruments are checked, and when the techniques
      have been tested. The delay in the removal of FBs is potentially harmful. The
      communication between the endoscopist and the anaesthesiologist is essential
      before the procedure to establish the plan of action; full cooperation is
      important and improves the outcome of endoscopy. CONCLUSIONS: Ingestion and or
      aspiration of FB in children are multifactorial in their aetiology, in their
      broad spectrum of different resolutions for the same FB and in the response of
      each patient to the treatment. Prevention remains the best treatment, implying an
      increased education of parents on age-appropriate foods and household items, and
      strict industry standards regarding the dimensions of toy parts and their secure
      containers.

PMID- 22365375
TI  - Non food foreign body injuries.
AB  - RATIONALE AND AIM: The aim of the present study is to acquire a better
      understanding of Non Food Foreign Bodies (NFFB) injuries in children with
      particular regard to the quantification of the risk of complications and
      hospitalization associated with patient characteristics, FB features, FB location
      and circumstances of the accident, as emerging from the SUSY Safe Web-Registry.
      METHODS: The present study uses data provided by the SUSY Safe Project, a DG
      SANCO co-funded project which was aimed to collect as many scientific data as
      possible regarding Foreign Bodies (FB) injuries in children aged 0-14 years and
      to serve as a basis for a knowledge-based consumer protection activity in the
      Europe market. FBs were characterized by size, shape and consistency. Descriptive
      statistics (absolute and relative number or median, I and III quartile according
      to the categorical or continuous variable, respectively) were calculated for each
      considered non food item characteristics; FB features distribution by children
      class age and site of obstruction were assessed. Two different outcomes were
      considered: hospitalization and complication. FBs which most frequently cause
      complications were identified. The association between children age, adult
      presence, object characteristics and outcomes was computed using crude odds
      ratios and the related 95% confidence intervals. RESULTS: 16,878 FB injuries in
      children aged 0-14 yrs have been recorded in the Susy Safe databases. FB type was
      specified in 10,564 cases; among them 7820 (74%) were due to a non food item.
      Almost two thirds of injuries occurred in patients 3 years or more old. 53% of
      patients were males, while 47% were females. When injury happened, the great part
      of children (86%) was playing. Almost 30% (2339) of injuries happened under
      adults' supervision. Complications occurred in 299 cases and the most documented
      was infections (10% of cases) followed by perforation (5%). CONCLUSIONS: The
      inhalation/aspiration of a FB, as well as the ingestion and the insertion in the
      orifices of a FB may result in significant morbidity. Particularly, long-standing
      or hazardous foreign bodies can cause extensive damage. Some objects, because of
      their composition, contour, or location, are particularly hazardous: for
      instance, objects with sharp edges pose a significant risk of laceration and
      perforation, while fragments of toys have been found only in 2 cases. Parents are
      frequently unconscious of hazard related with some objects and they are not
      adequately able to promptly recognize dangerous objects and risky situations.
      Moreover, also clinicians seem to pay little attention to adult role in the
      dynamic of the accident: in fact in case series descriptions, data regarding
      adult presence are often under-reported. On the contrary, since many injuries to
      children cannot be prevented without some degree of active behavior on the part
      of parents, the dissemination of information regarding safe behaviors and the
      implementation of educational strategies aiming to improve parent's attention
      toward this issue could be fundamental in preventing injuries and need to be
      promoted by family pediatricians and health practitioners.

PMID- 22365377
TI  - Predictors of walking performance and walking capacity in people with lumbar
      spinal stenosis, low back pain, and asymptomatic controls.
AB  - OBJECTIVE: To examine predictors of community walking performance and walking
      capacity in people with lumbar spinal stenosis (LSS), compared with people with
      low back pain and asymptomatic control subjects. DESIGN: Retrospective analysis.
      SETTING: University spine program. PARTICIPANTS: Participants (N=126; 50 LSS, 44
      low back pain, 32 asymptomatic control subjects) aged 55 to 80 years were
      studied. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Seven-day
      community walking distance measured by pedometer (walking performance) and a 15
      minute walking test (walking capacity). All participants had lumbosacral magnetic
      resonance imaging, electrodiagnostic testing, and a history and physical
      examination, including a history of pain and neurologic symptoms, a straight leg
      raise test, and tests for directional symptoms, reflexes, strength, and nerve
      tension signs. The study questionnaire included demographic information, a
      history of back/leg pain, and questions about walking, exercise frequency, and
      pain level, as well as the standardized Quebec Back Pain Disability Scale.
      RESULTS: Body mass index (BMI), pain, age, and female sex predicted walking
      performance (r(2)=.41) and walking capacity (r(2)=.41). The diagnosis of LSS
      itself had no clear relationship with either walking variable. Compared with the
      asymptomatic group, LSS participants had significantly lower values for all
      walking parameters, with the exception of stride length, while there was no
      significant difference between the LSS and low back pain groups. CONCLUSIONS:
      BMI, pain, female sex, and age predict walking performance and capacity in people
      with LSS, those with low back pain, and asymptomatic control subjects. While pain
      was the strongest predictor of walking capacity, BMI was the strongest predictor
      of walking performance. Average pain, rather than leg pain, was predictive of
      walking performance and capacity. Obesity and pain are modifiable predictors of
      walking deficits that could be targets for future intervention studies aimed at
      increasing walking performance and capacity in both the low back pain and LSS
      populations.

PMID- 22365378
TI  - Equilibrium and kinetic studies on biosorption of 2,4,6-trichlorophenol from
      aqueous solutions by Acacia leucocephala bark.
AB  - Biosorption of 2,4,6-trichlorophenol (2,4,6-TCP) from aqueous solution by biomass
      prepared from Acacia leucocephala bark, an agricultural solid waste has been
      investigated in the present study. All the experiments are carried out by batch
      mode technique. The resulting biosorbent was characterized by Fourier transform
      infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) techniques.
      The effect of experimental parameters such as contact time, effect of pH (2-10),
      initial concentration of adsorbate (50-200 mg L(-1)) and amount of biosorbent
      dosage was evaluated. The removal was found to be pH dependent, and maximum
      removal was found to be at pH 5.0. The equilibrium time was found to be 3h. The
      biosorbent dose was increased, and the percentage removal of 2,4,6-TCP was
      increased, while the adsorption capacity at equilibrium q(e) (mg g(-1)) (amount
      of 2,4,6-TCP loaded per unit weight of adsorbent) decreased. Biosorption kinetic
      and isotherm studies showed the pseudo-second-order kinetics with a good
      correlation coefficient (R(2)=0.999), and both Langmuir and Freundlich isotherms
      were the best choices to describe the adsorption behaviors. The maximum monolayer
      biosorption capacity of A. leucocephala bark for 2,4,6-TCP was found to be 256.4
      mg g(-1), at 30+/-1 degrees C according to Langmuir model. This study
      demonstrated for the first time that the A. leucocephala bark could be an
      alternative for more costly adsorbents used for removal of 2,4,6-TCP from aqueous
      media.

PMID- 22365379
TI  - Estimating spatial and temporal variations of the reproduction number for highly
      pathogenic avian influenza H5N1 epidemic in Thailand.
AB  - Since 2003, highly pathogenic avian influenza (HPAI) H5N1 virus has spread,
      causing a pandemic with serious economic consequences and public health
      implications. Quantitative estimates of the spread of HPAI H5N1 are needed to
      adapt control measures. This study aimed to estimate the variations of the
      reproduction number R in space and time for the HPAI H5N1 epidemic in Thailand.
      Transmission between sub-districts was analyzed using three different and
      complementary methods. Transmission of HPAI H5N1 was intense (R(t)>1) before
      October 2004, at which point the epidemic started to progressively fade out
      (R(t)<1). The spread was mainly local, with 75% of the putative distances of
      transmission less than 32km. The map of the mean standardized ratio of
      transmitting the infection (sr) showed sub-districts with a high risk of
      transmitting infection. Findings from this study can contribute to discussions
      regarding the efficacy of control measures and help target surveillance programs.

PMID- 22365380
TI  - Oocyte slow freezing using a 0.2-0.3 M sucrose concentration protocol: is it
      really the time to trash the cryopreservation machine?
AB  - OBJECTIVE: To update results on outcomes with frozen/thawed oocytes using a
      differential sucrose concentration during dehydration (0.2 M) and rehydration
      (0.3 M), combined with a one-step propanediol exposure. DESIGN: Retrospective
      cohort study. SETTING: Private IVF centers. PATIENT(S): Infertile couples
      undergoing IVF treatment. INTERVENTION(S): Oocyte thawing cycles between May 2004
      and December 2010. MAIN OUTCOME MEASURE(S): Survival, fertilization, and cleavage
      rates were reported to evaluate biological outcomes. Clinical pregnancy and
      implantation rates were analyzed as markers of efficiency. RESULT(S): Three
      hundred forty-two patients and 443 cycles were monitored; the survival was 71.8%,
      fertilization 77.9%, and of the embryos obtained 83.8% were classified as grade 1
      and 2. Three hundred ninety-four transfers were performed, resulting in 90
      pregnancies. The pregnancy rate per transfer was 22.8% and per patient was 26.3%,
      with 122 gestational sacs. The implantation rate per embryo was 13.5%. Patients
      were divided into three groups according to their age: <= 34 years (group A), 35
      38 years (group B), and >= 39 years (group C). Biological outcomes were
      comparable in all three groups, whereas the pregnancy rate per transfer was
      higher in the first group (27.7% vs. 21.4% and 17.6%). The implantation rates per
      injected egg were 11.8%, 8.0%, and 7.5% for the three groups, respectively.
      CONCLUSION(S): The biological and clinical data obtained on 443 cycles are
      consistent with our previous results showing that slow freezing of oocytes can be
      a valid tool in IVF practice when performed with a suitable protocol.

PMID- 22365381
TI  - Microarray expression profiling in adhesion and normal peritoneal tissues.
AB  - OBJECTIVE: To identify molecular markers associated with adhesion and normal
      peritoneal tissue using microarray expression profiling. DESIGN: Comparative
      study. SETTING: University hospital. PATIENT(S): Five premenopausal women.
      INTERVENTION(S): Adhesion and normal peritoneal tissue samples were obtained from
      premenopausal women. Ribonucleic acid was extracted using standard protocols and
      processed for hybridization to Affymetrix Whole Transcript Human Gene Expression
      Chips. Microarray data were obtained from five different patients, each with
      adhesion tissue and normal peritoneal samples. Real-time polymerase chain
      reaction was performed for confirmation using standard protocols. MAIN OUTCOME
      MEASURE(S): Gene expression in postoperative adhesion and normal peritoneal
      tissues. RESULT(S): A total of 1,263 genes were differentially expressed between
      adhesion and normal tissues. One hundred seventy-three genes were found to be up
      regulated and 56 genes were down-regulated in the adhesion tissues compared with
      normal peritoneal tissues. The genes were sorted into functional categories
      according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down
      regulated genes were identified with functions potentially relevant to the
      pathophysiology of postoperative adhesions. We evaluated and confirmed expression
      of 12 of these specific genes via polymerase chain reaction. CONCLUSION(S): The
      pathogenesis, natural history, and optimal treatment of postoperative adhesive
      disease remains unanswered. Microarray analysis of adhesions identified specific
      genes with increased and decreased expression when compared with normal
      peritoneum. Knowledge of these genes and ontologic pathways with altered
      expression provide targets for new therapies to treat patients who have or are at
      risk for postoperative adhesions.

PMID- 22365382
TI  - An investigation into the relationship between the metabolic profile of
      follicular fluid, oocyte developmental potential, and implantation outcome.
AB  - OBJECTIVE: To determine whether metabolomic analysis of follicular fluid could
      prove a useful noninvasive technique for the selection of viable oocytes and
      embryos. DESIGN: Metabolomic analysis based on proton nuclear magnetic resonance
      ((1)H NMR) performed on follicular fluid collected from in vitro fertilization
      (IVF) patients. SETTING: A university research center and a private fertility
      clinic. PATIENT(S): Fifty-eight women undergoing IVF treatment. INTERVENTION(S):
      Follicular fluid collected at the time of oocyte retrieval. MAIN OUTCOME
      MEASURE(S): Metabolomic profile, assessment of oocyte developmental potential and
      embryo viability. RESULT(S): The metabolomic profile of follicular fluid from
      follicles where the oocyte resulted in a fertilized egg that failed to cleave (n
      = 9) was distinctly different from that where oocytes developed into early
      cleavage-stage embryos. Discriminating metabolites included glucose, lactate,
      choline/phosphocholine, and lipoproteins. Comparison of follicular fluid from
      women who subsequently had a positive beta human chorionic gonadotropin (n = 10)
      to those who were unsuccessful in achieving a pregnancy (n = 12) revealed
      metabolic differences that were correlated to cycle outcome. CONCLUSION(S):
      Differences in the metabolite composition of follicular fluid correlate with the
      developmental competence of the human oocyte. Therefore, metabolomic profiling of
      follicular fluid may prove to be an important technique in gamete/embryo
      selection.

PMID- 22365383
TI  - NPY suppressed development of experimental autoimmune encephalomyelitis in Dark
      Agouti rats by disrupting costimulatory molecule interactions.
AB  - Neuropeptide Y (NPY) suppressed clinical experimental autoimmune
      encephalomyelitis (EAE) and reduced numbers of CD28+, CD11b+ and CD80+ cells
      among spinal cord infiltrating cells at the peak of disease in Dark Agouti rat
      strain. Suppression of EAE was accompanied by the reduced expression of
      costimulatory CD80 and CD86 molecules on ED1+ macrophages and OX62+ dendritic
      cells in draining lymph nodes during the inductive phase of EAE. An inhibitor of
      dipeptidyl peptidase 4, an enzyme which terminates the action of NPY on Y1
      receptor subtype, did not sustain the suppressive effect of NPY on the EAE
      development, suggesting involvement of Y2 and Y5 receptors.

PMID- 22365384
TI  - Global gray matter changes in posterior cortical atrophy: a serial imaging study.
AB  - BACKGROUND: Posterior cortical atrophy (PCA) is a neurodegenerative condition
      predominantly associated with Alzheimer's disease (AD) pathology. Cross-sectional
      imaging studies have shown different atrophy patterns in PCA patients compared
      with typical amnestic Alzheimer's disease (tAD) patients, with greatest atrophy
      commonly found in posterior regions in the PCA group, whereas in the tAD group,
      atrophy is most prominent in medial temporal lobe regions. However, differential
      longitudinal atrophy patterns are not well understood. METHODS: This study
      assessed longitudinal changes in brain and gray matter volumes in 17 PCA
      patients, 16 tAD patients, and 18 healthy control subjects. Both patient groups
      had symptom durations of approximately 5 years. RESULTS: Progressive gray matter
      losses in both PCA and tAD patients were relatively widespread throughout the
      cortex, compared with control subjects, and were not confined to areas related to
      initial symptomatology. A multivariate classification analysis revealed a
      statistically significant group separation between PCA and tAD patients, with
      72.7% accuracy (P < .01). CONCLUSION: Progression from an initially focal
      presentation to a more global pattern suggests that these different clinical
      presentations of AD might converge pathologically over time.

PMID- 22365385
TI  - What can global positioning systems tell us about the contribution of different
      types of urban greenspace to children's physical activity?
AB  - Urban greenspace is hypothesised to be an important location for physical
      activity in children, but their actual use of the resource to be active is not
      well known. In this study, global positioning systems (GPS) and accelerometers
      were used to measure activity within green environments for 902 English children
      aged 11-12. We summarised activity intensities in different types of greenspace
      on weekday evenings, weekend days and by season. Around half of outdoor moderate
      vigorous activity took place in greenspace at the weekend and use was consistent
      across seasons. The findings suggest the importance of certain types of
      greenspace to children's physical activity.

PMID- 22365386
TI  - Infectious Insecurities: H1N1 and the politics of emerging infectious disease.
AB  - Responses to the 2009 H1N1 pandemic, and criticisms of those responses, were
      framed by issues endemic to the meeting of 'health' and 'security' as governing
      domains. Offering an editorial introduction to the selection of papers in this
      special issue, it is suggested that existing scholarship in the emerging field of
      'health security' can be categorized according to realist-advocacy, historical
      analytic, problematization and critical-inequality approaches. In contributing to
      this literature through an event-based focus on the pandemic, the papers embrace
      the opportunity to examine health security architectures acting and interacting
      'in the event', to not only speculate over the possible implications of this
      governing trope, but to review them. Questions of the scales of governance and
      associated forms of expertise, the implications of differing modes of governance
      (from preparedness to surveillance to forms of intervention), and the role of
      health inequalities in the patterning of the pandemic are identified as key
      themes running across the papers.

PMID- 22365387
TI  - Biodegradation of bensulphuron-methyl by a novel Penicillium pinophilum strain,
      BP-H-02.
AB  - A fungal strain able to rapidly degrade bensulphuron-methyl (BSM), called BP-H
      02, was isolated for the first time from soil that had been contaminated with BSM
      for several years. BP-H-02 can use BSM as the sole carbon and energy source for
      growth in a mineral salt medium. Based on morphological and internal transcribed
      spacer (ITS) analysis, BP-H-02 was identified as Penicillium pinophilum. Under
      optimal conditions (pH 6.5, temperature 30  degrees C and 200 mg/L VSSinoculum),
      more than 87% of the initially added BSM (50mg/L) was degraded after 60 h.
      Metabolites were identified as 2-amino-4,6-dimethoxypyrimidine and 1-(4,6
      dimethoxypyrimidin-2-yl) urea by liquid chromatography-mass spectrometry (LC-MS),
      and a possible degradation pathway was deduced. In a soil bioremediation
      experiment, inoculation of soil with BP-H-02 promoted the degradation of BSM more
      effectively than did the control. These results revealed that BP-H-02 can
      biodegrade bensulphuron-methyl efficiently and could potentially be used to
      bioremediate sulphonylurea herbicides contamination.

PMID- 22365388
TI  - Preparation and electrochemical properties of Ce-Ru-SnO2 ternary oxide anode and
      electrochemical oxidation of nitrophenols.
AB  - A cerium doped ternary SnO(2) based oxides anode that is CeO(2)-RuO(2)-SnO(2) (Ce
      Ru-SnO(2)) anode, was prepared by facile thermal decomposition technique. XRD was
      used to characterize the crystal structures of modified SnO(2) anodes.
      Electrochemical impedance spectroscopy (EIS) and accelerated life test were also
      utilized to study the electrochemical property of Ce-Ru-SnO(2) anode. The results
      indicated that Ce-Ru-SnO(2) anode possessed smaller charge transfer resistance
      and longer service life than other modified SnO(2) anodes. Oxidants, such as
      hydroxyl radicals, hydrogen peroxide and hypochlorite ions were determined.
      Electrochemical oxidation of nitrophenols (NPs) were conducted and compared with
      previous studies. The degradation of nitrophenols revealed two distinguishing
      laws for mononitrophenol and multinitrophenols. The Ce-Ru-SnO(2) anode is
      considered to be a promising material for the treatment of organic pollutants due
      to its high electrochemical activity and benign stability.

PMID- 22365389
TI  - Traumatic tympanic membrane perforations: a study of etiology and factors
      affecting outcome.
AB  - OBJECTIVE: The purposes of this study were to determine the factors involved in
      the spontaneous healing and to profile the various etiologies of traumatic
      tympanic membrane (TM) perforation. METHODS: A retrospective review was performed
      on 729 cases of traumatic TM perforation diagnosed in the emergency department
      and outpatient clinic from January 2007 to March 2011. RESULTS: A total 641
      patients with traumatic TM perforations were enrolled in the study. The group
      consisted of 320 male and 321 female patients with a mean age of 33.6 years (3-79
      years). The types of trauma included compression injury (554 patients), blast
      injury (55 patients), and instrumental injury (32 patients). The causes of
      conflict by a slap or a fist were spouse or lover (52%), parents and sibling
      (3%), school teachers (4%), schoolmate (12%), state police and prisoner (7%), and
      blow against the ear during street fight (22%). Of the 641, 137 were lost during
      follow-up; of the remaining 504, perforations closed spontaneously in 451 (89%),
      within a mean of 27.4 days. Wet perforations with bloody or watery discharge
      significantly improved the healing rate (P < .01) and shortened the average
      perforation closure time (P < .01), as compared with dry perforations. Although
      the perforation that involved malleus or umbo damage did not significantly affect
      the healing rate (P > .05), a significantly prolonged closure time (41.6 vs 23.8
      days) was observed as compared with no damage. However, the curled edges did not
      also affect the outcome of spontaneous healing; the healing rate was 91% and 88%
      (P > .05), and the average closure time was 28.1 and 26.7 days (P > .05),
      respectively, for with and without curler edges. By perforation size, the overall
      healing rate was 92% and 54% (P < .01), and the average closure time was 22.8 and
      47.3 days (P < .01), respectively, for small and larger perforations. Moreover, 7
      patients had neomembrane formation on follow-up, 2 developed cholesteatoma, 1
      developed tympanosclerosis, and 1 developed facial paralysis. CONCLUSION: In our
      experience, domestic violence and street fight were the most common causes of the
      traumatic TM perforation. Traumatic TM perforations have excellent prognosis.
      However, preexisting tympanosclerosis and the perforation that involved malleus
      or umbo damage could lengthen the healing time of perforation, Wet perforations
      with bloody or watery discharge accelerate the healing, but the curled edges did
      not affect the outcome of spontaneous healing.

PMID- 22365390
TI  - Missing fish bone: case report and literature review.

PMID- 22365391
TI  - Phosphorus nutrition alters herbicide toxicity on Daphnia magna.
AB  - We examined the effects of algal phosphorus (P) content on the toxicity of a
      common herbicide, WeatherMAX Roundup (WMR), to Daphnia magna. The growth,
      reproduction, and survival of D. magna were assessed with animals consuming
      different food P content and exposed to different concentrations of WMR. While
      the effects of WMR on mortality increased with time of exposure, we found no
      interactive effects between food P content and WMR on daphnid survival over any
      of time periods examined (4, 10, or 20 days). In contrast, we found interactive
      effects of WMR and dietary P content on Daphnia juvenile growth (measured after 6
      days) with the greatest effects of WMR on animals consuming P-rich food.
      Interactive effects of WMR and food P content were also found on some aspects of
      Daphnia's reproduction (number of broods and total offspring production) with P
      deprived animals most affected by WMR exposure. Our results demonstrate that P
      nutrition can alter the toxicity of WMR on key life-history traits of D. magna
      but that the nature and strength of these effects differ among the traits
      examined. The effects of P-nutrition on WMR-toxicity likely reflect changes in
      the exposure to and/or incorporation of WMR into animal bodies associated with
      changes in growth resulting from poor nutrition and the ability of animals to
      repair ensuing damage. Given the widely variable nutritional state of animals in
      nature, this differential toxicity of WMR with food quality warrants further
      study and should be incorporated in future risk assessments of this widely used
      chemical.

PMID- 22365392
TI  - Isolation, identification and characterization of Bacillus amyloliquefaciens BZ
      6, a bacterial isolate for enhancing oil recovery from oily sludge.
AB  - Over 100 biosurfactant-producing microorganisms were isolated from oily sludge
      and petroleum-contaminated soil from Shengli oil field in north China. Sixteen of
      the bacterial isolates produced biosurfactants and reduced the surface tension of
      the growth medium from 71 to <30 mN m(-1) after 72 h of growth. These bacteria
      were used to treat oily sludge and the recovery efficiencies of oil from oily
      sludge were determined. The oil recovery efficiencies of different isolates
      ranged from 39% to 88%. Bacterial isolate BZ-6 was found to be the most efficient
      strain and the three phases (oil, water and sediment) were separated
      automatically after the sludge was treated with the culture medium of BZ-6. Based
      on morphological, physiological characteristics and molecular identification,
      isolate BZ-6 was identified as Bacillus amyloliquefaciens. The biosurfactant
      produced by isolate BZ-6 was purified and analyzed by high performance liquid
      chromatography-electrospray ionization tandem mass spectrometry. There were four
      ion peaks representing four different fengycin A homologues.

PMID- 22365393
TI  - Structural variation of the superintegron in the toxigenic Vibrio cholerae O1 El
      Tor.
AB  - OBJECTIVE: To understand the genetic structures and variations of the
      superintegron (SI) in Vibrio cholerae isolated in the seventh cholera pandemic.
      METHODS: Polymerase chain reaction scanning and fragment sequencing were used.
      Sixty toxigenic V. cholerae O1 El Tor strains isolated between 1961 and 2008 were
      analyzed. RESULTS: Some variations were found, including insertions,
      replacements, and deletions. Most of the deletions were probably the result of
      recombination between V. cholerae repeat sequences. The majority of the
      variations clustered together. The SIs of the strains isolated in the 1960s and
      1970s showed more diversity, whereas SI cassette variations in strains isolated
      in the 1990s and after were lower, with ~24 kb signature sequence deletion. This
      indicates the predominant SI in the host during the epidemic in the 1990s and
      after. The insertion cassettes suggested the mobilization from the SIs of other
      V. cholerae serogroups and Vibrio mimicus. CONCLUSION: The study revealed that
      structural variations of SIs were obvious in the strains isolated in epidemics in
      different decades, whereas the divergence was based on syntenic structure of SIs
      in these El Tor strains. Also, the continuing cassette flows in the SIs of the
      host strains during the seventh cholera pandemics were displayed.

PMID- 22365394
TI  - In vitro evaluation of cytotoxicity and oxidative stress induced by multiwalled
      carbon nanotubes in murine RAW 264.7 macrophages and human A549 lung cells.
AB  - OBJECTIVE: To investigate in vitro cytotoxicity and oxidative stress response
      induced by multiwalled carbon nanotubes (MWCNTs). METHODS: Cultured macrophages
      (murine RAW264.7 cells) and alveolar epithelium cells type II (human A549 lung
      cells) were exposed to the blank control, DNA salt control, and the MWCNTs
      suspensions at 2.5, 10, 25, and 100 MUg/mL for 24 h. Each treatment was evaluated
      by cell viability, cytotoxicity and oxidative stress. RESULTS: Overall, both cell
      lines had similar patterns in response to the cytotoxicity and oxidative stress
      of MWCNTs. DNA salt treatment showed no change compared to the blank control. In
      both cell lines, significant changes at the doses of 25 and 100 MUg/mL treatments
      were found in cell viabilities, cytotoxicity, and oxidative stress indexes. The
      reactive oxygen species (ROS) generation was also found to be significantly
      higher at the dose of 10 MUg/mL treatment, whereas no change was seen in most of
      the indexes. The ROS generation in both cell lines went up in minutes, reached
      the climax within an hour and faded down after several hours. CONCLUSION:
      Exposure to MWCNTs resulted in a dose-dependent cytotoxicity in cultured RAW264.7
      cells and A549 cells, that was closely correlated to the increased oxidative
      stress.

PMID- 22365395
TI  - Optimization of the assembly efficiency for lidamycin chromophore bound to its
      apoprotein: a case study using orthogonal array.
AB  - OBJECTIVE: Lidamycin (LDM) can be dissociated to an apoprotein (LDP) and an
      active enediyne chromophore (AE). The detached AE can reassemble with its LDP
      containing fusion protein to endow the latter with potent antitumor activity.
      However, the reassembly of AE with LDP is affected by several factors. Our aim
      was to optimize the assembly efficiency of the AE with a LDP-containing fusion
      protein and investigate the influence of several factors on the assembly
      efficacy. METHODS: A method based on RP-HPLC was developed to analyze the
      assembly rate, and an orthogonal experimental design L(9) (3(4)) was used to
      investigate the effects of temperature, assembly time, pH and molecular ratio of
      LDP-containing fusion protein to AE on the assembly rate. Furthermore, the
      determined optimum conditions for the assembly rate of the LDP-containing fusion
      protein with AE were applied and evaluated. RESULTS: A calibration curve based on
      the LDM micromolar concentration against the peak-area of AE by HPLC was
      obtained. The order in which individual factors in the orthogonal experiment
      affected the assembly rate were temperature>time>pH>molar ratio of AE to protein
      and all were statistically significant (P<0.01). The optimal assembly conditions
      were temperature at 10 degrees C, time of 12 h, pH 7.0, and the molar ratio of
      AE: protein of 5:1. The assembly rate of AE with a LDP-containing fusion protein
      was improved by 23% after condition optimization. CONCLUSION: The assembly rate
      of chromophore of lidamycin with its LDP-containing fusion protein was improved
      after condition optimization by orthogonal design, and the optimal conditions
      described herein should prove useful for the development of this type of LDP
      containing fusion protein.

PMID- 22365396
TI  - Establishment of hamster- and human-PRNP transgenic mice.
AB  - OBJECTIVE: To create transgenic mice expressing hamster- and human-PRNP as a
      model for understanding the physiological function and pathology of prion protein
      (PrP), as well as the mechanism of cross-species transmission of transmissible
      spongiform encephalopathies (TSEs). METHODS: Hamster and human-PRNP transgenic
      mice were established by conventional methods. The copy number of integrated PRNP
      in various mouse lines was mapped by real-time PCR. PRNP mRNA and protein levels
      were determined by semi-quantitative RT-PCR, real-time RT-PCR, and western blot
      analysis. Histological analyses of transgenic mice were performed by hematoxylin
      and eosin (H & E) staining and immunohistochemical (IHC) methods. RESULTS:
      Integrated PRNP copy number in various mouse lines was 53 (Tg-haPrP1), 18 (Tg
      huPrP1), 3 (Tg-huPrP2), and 16 (Tg-huPrP5), respectively. Exogenous PrPs were
      expressed at both the transcriptional and translational level. Histological
      assays did not detect any abnormalities in brain or other organs. CONCLUSION: We
      have established one hamster-PRNP transgenic mouse line and three human-PRNP
      transgenic mouse lines. These four transgenic mouse lines provide ideal models
      for additional research.

PMID- 22365397
TI  - Dietary iodine intake in the Chinese population.
AB  - OBJECTIVE: To evaluate dietary iodine intake and its potential risks among the
      Chinese population. METHODS: Individual dietary iodine intake was calculated
      using food consumption data multiplying by iodine concentration in foods, table
      salt and drinking water, followed by summing, and then compared with the
      corresponding age-specific reference values, including Upper Intake Level (UL)
      and Recommended Nutrient Intake (RNI). RESULTS: In areas with water iodine
      concentration (WI) lower than 150 MUg/L, 80.8% of residents had iodine intake
      between the RNI and UL, 5.8% higher than UL, and the remaining (13.4%) lower than
      RNI if iodized salt was consumed. However, in the uniodized salt consumption
      scenario, only 1.0% of residents between RNI and UL, 1.4% higher than UL, and a
      large part of residents (97.6%) lower than RNI. In areas with WI higher than 150
      MUg/L, all residents had iodine intake between RNI and UL if iodized salt was
      consumed, except 10.5% and 24.9% of residents higher than UL in areas with WI at
      150-300 MUg/L and higher than 300 MUg/L respectively. However, in the uniodized
      salt consumption scenario, only 1.5% and 1.7% of residents had higher iodine
      intake than UL respectively. CONCLUSION: The findings suggested that in general,
      the dietary iodine intake by the Chinese population was appropriate and safe at
      the present stage. People in areas with WI lower than 150 MUg/L were more likely
      to have iodine deficiency. While people in areas with WI higher than 150 MUg/L
      were more likely to have excessive iodine intake if iodized salt was consumed.

PMID- 22365398
TI  - Effect of aluminum hydroxide adjuvant on the immunogenicity of the 2009 pandemic
      influenza A/H1N1 vaccine: multi-level modeling of data with repeated measures.
AB  - OBJECTIVE: To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on
      the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine. METHODS: In a multicenter,
      double-blind, randomized, placebo-controlled trial, participants received two
      doses of split-virion formulation containing 15 MUg hemagglutinin antigen, with
      or without aluminum hydroxide (Al-OH). We classified the participants into six
      age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and
      3-7 years) and obtained four blood samples from each participant on days 0, 21,
      35, and 42 following the first dose of immunization. We assessed vaccine
      immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination
      inhibiting antibody. We used a two-level model to evaluate the fixed effect of
      aluminum Al-OH and other factors, accounting for repeated measures. RESULTS: The
      predictions of repeated measurement on GMTs of formulations with or without Al
      OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced
      immunogenicity after controlling for time post immunization, age-group and
      gender. CONCLUSION: The Al-OH adjuvant does not increase but actually reduces the
      immunogenicity of the split-virion pH1N1 vaccine.

PMID- 22365399
TI  - Correlation of seven biological factors (Hsp90a, p53, MDM2, Bcl-2, Bax,
      Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic
      large-cell lymphoma.
AB  - OBJECTIVE: To explore correlation of seven apoptosis-related proteins (Hsp90a,
      p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes
      of ALK+ anaplastic large-cell lymphoma (ALCL). METHODS: Using
      immunohistochemistry and immunofluorescence double staining methods, the
      expressions of these seven apoptosis-associated proteins were studied to clarify
      their relationship with clinical outcomes of 36 ALK+ and 25 ALK-systemic ALCL
      patients enrolled between 1996 and 2006. The relationship of these apoptosis
      regulating proteins with NPM-ALK status was also evaluated with the tyrosine
      inhibitor herbimycin A (HA) in vitro by immunocytochemistry, Western blotting and
      flow cytometric assays. RESULTS: The presence of Hsp90alpha-, MDM2-, Bax-,
      Cytochrome C, and Cleaved caspase3-positive tumor cells was found significantly
      different in ALK+ and ALK-ALCLs, which was correlated with highly favorable
      clinical outcome. The Bcl-2- and p53-positive tumor cells were found in groups of
      patients with unfavorable prognosis. Inhibition of NPM-ALK by HA could reactivate
      the p53 protein and subsequent apoptosis-related proteins and therefore induced
      apoptosis in ALK+ ALCL cells. CONCLUSION: Our results suggest that these seven
      proteins might be involved in apoptosis regulation and associated with clinical
      outcome of ALK+ systemic ALCLs. We also reveal a dynamic chain relation that NPM
      ALK regulates p53 expression and subsequent apoptosis cascade in ALK+ ALCLs.

PMID- 22365400
TI  - The effects of demographic features on differences in sensitivity between PCL-C
      and SCL-90 scores in a follow-up study in secondary school students in the
      Wenchuan earthquake region.
AB  - OBJECTIVE: To analyze the sensitivity of effect factors between the PCL-C and the
      SCL-90, to provide evidence for social psychological crisis screening and post
      trauma interventions. METHODS: We administered the PCL-C and SCL-90 to screen for
      PTSD and other psychological problems among students who survived the disaster
      and continued their school studies. The surveys were carried out 3, 6, 9, and 12
      months after the earthquake. A bivariate 2-level logistic model was used to
      explore the different levels of sensitivity among students. The factors
      influencing the relationships between PTSD and depression, and between PTSD and
      anxiety were examined. RESULTS: We analyzed data from 1 677 students, revealing
      that female students in higher grades were more likely to exhibit symptoms of
      depression, rather than PTSD, compared with the control group (males in lower
      grades), and the difference was significant (P<0.05). In contrast, ethnic
      minorities were more likely to exhibit PTSD symptoms compared to the others. In
      addition, female students were more likely to exhibit symptoms of anxiety than
      PTSD. Other effects that did not reach statistical significance were suggested to
      have a similar influence on PTSD, depression, and anxiety. CONCLUSION: After a
      natural disaster, specific aspects of depression and anxiety should be examined,
      avoiding an overemphasis on PTSD in social psychological crisis interventions.

PMID- 22365401
TI  - Coping as a mechanism linking stressful life events and mental health problems in
      adolescents.
AB  - OBJECTIVE: Although stressful life events represent an etiologic factor of mental
      health problems in adolescents, few studies have been conducted to address
      mechanisms linking the stress-psychopathology relation. The present study was
      designed to examine coping as a mediate factor on the relationship between
      stressful life events and symptoms of anxiety and depression. METHODS: The
      participants were 13 512 students from eight cities of China, who participated in
      a school-based survey. Data were collected by a questionnaire comprising coping,
      stressful life events, anxiety, and depressive symptoms. As a model, a series of
      regression equations were used to examine whether coping mediated the association
      between stressful life events and symptoms of anxiety and depression. RESULTS:
      Each dimension of stressful life events showed significant correlation with
      anxiety, depression and coping (all P<0.001). In the model to analyze mediate
      effects, all standardized coefficients (beta) were significant (all P<0.01),
      indicating marked mediator effects. Furthermore, negative coping might account
      for more mediate effects than positive coping on this relationship. CONCLUSION:
      Coping partially mediated the relationship between stressful life events and
      mental health during adolescence. This study highlighted an important public
      health priority for preventive interventions targeting stress-related
      psychopathology, and for further promoting adolescents' mental health.

PMID- 22365402
TI  - Effect of water hardness on the toxicity of cobalt and nickel to a freshwater
      fish, Capoeta fusca.
AB  - OBJECTIVE: To determine the effects of water hardness on the toxicities of cobalt
      (Co) and nickel (Ni) to a freshwater fish, Capoeta fusca. METHODS: Toxicity was
      investigated by static bioassay. Fish were exposed to cobalt (as CoCl(2)) and
      nickel (as NiCl(2)) for 96 h in waters with two levels of hardness ("hard" and
      "very hard", nominally 130 mg/L and 350 mg/L as CaCO(3), respectively). RESULTS:
      Water hardness had a significant effect on the acute toxicity of both elements.
      The 96 h LC(50) values for Co were 91.7 mg/L and 204.8 mg/L in hard and very hard
      waters, respectively, and for Ni the 96 h LC(50) values were 78.0 mg/L and 127.2
      mg/L, respectively. CONCLUSION: The fish were more sensitive to Co and Ni
      toxicity in hard water than in very hard water; very hard water protects C. fusca
      against the toxicity of Co and Ni.

PMID- 22365403
TI  - ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human
      fetal lung fibroblasts.
AB  - OBJECTIVE: This study aims to investigate and compare the toxic effects of four
      types of metal oxide (ZnO, TiO(2), SiO(2,) and Al(2)O(3)) nanoparticles with
      similar primary size (~20 nm) on human fetal lung fibroblasts (HFL1) in vitro.
      METHODS: The HFL1 cells were exposed to the nanoparticles, and toxic effects were
      analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258
      staining. RESULTS: The results show that the four types of metal oxide
      nanoparticles lead to cellular mitochondrial dysfunction, morphological
      modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the
      toxic effects are obviously displayed in dose-dependent manner. ZnO is the most
      toxic nanomaterials followed by TiO(2), SiO(2), and Al(2)O(3) nanoparticles in a
      descending order. CONCLUSION: The results highlight the differential cytotoxicity
      associated with exposure to ZnO, TiO(2), SiO(2), and Al(2)O(3) nanoparticles, and
      suggest an extreme attention to safety utilization of these nanomaterials.

PMID- 22365404
TI  - Association of polymorphisms of STAT6 and SO(2) with Chinese childhood asthma: a
      case-control study.
AB  - OBJECTIVE: To investigate the association of polymorphisms of STAT6 gene and air
      pollutants of PM(10), NO(2), and SO(2), with asthma in Chinese children. METHODS:
      418 subjects aged 14 years and under were recruited in a case-control study. The
      association between STAT6 polymorphisms and childhood asthma were tested by
      allele frequency, genotype analysis, and MDR analysis. Exposure to outdoor air
      pollutants was estimated by a 5-day moving average level. Statistical analyses
      were performed with SAS 9.1 software. RESULTS: Only 3 alleles of GT repeats at
      exon 1 of STAT6 were found in Chinese children. C258T and T710C were 2 new SNPs
      of STAT6 at 3'-UTR. Children who carried T allele of C258T were more common in
      asthma children than in control subjects (P<0.05). The MDR analysis showed that
      GT repeats, C258T and T710C of STAT6 polymorphisms interacted together in leading
      to susceptibility to childhood asthma among Chinese people. After confounding
      factors were controlled, such as SNP C258T, family history of asthma, frequency
      of influenza within a year, the 5-day average of SO(2) was tested to be a key
      risk factor of asthma in Chinese children (P<0.05). CONCLUSION: Chinese children
      differed in polymorphisms of STAT6 and in its relation with childhood asthma.

PMID- 22365405
TI  - The relationship between polymorphisms of interleukin-4 gene and silicosis.
AB  - OBJECTIVE: To explore the relationship between polymorphisms of interleukin-4 (IL
      4) gene (-33, +45, intron3, +429, +448) and the susceptibility of silicosis.
      METHODS: A case-control study was carried out. 101 silicosis patients were
      selected as cases. As strictly matching, 121 of non silicosis workers were
      selected as the controls. The polymophisms of IL-4 (five locus) were detected by
      the method of polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) techniques. RESULTS: The GA genotype in the IL-4+429 locus and the CC
      genotype in the IL-4+448 locus were found. The frequencies of AA, GG and AG of IL
      4+45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were
      62.0%, 11.6%, and 26.4%. The differences between cases and controls were not
      significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the
      cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and
      29.8%. The differences were not significant. The frequencies of TT, CC, and CT in
      -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were
      69.4%, 4.1%, and 26.4%. The differences were significant (P=0.034). CONCLUSION:
      The relationship between genetic polymorphism of IL-4-33 site and silicosis has
      been found and -33TT is a protective genotype for silicosis.

PMID- 22365406
TI  - Meta-analysis of cytochrome P4501A1 MspI gene polymorphism and childhood acute
      leukemia.
AB  - OBJECTIVE: To investigate the relationship between cytochrome P4501A1 (CYP1A1)
      Msp I gene polymorphism and childhood acute leukemia (AL). METHODS: Relevant
      literature was extensively searched and screened by Pubmed and Wanfang Database,
      Chinese Science Journal Database and Chinese Journal Net. Various data
      consolidation, combined OR values and their 95% CI were tested by RevMan 4.2;
      Funnel plots were used for the bias analysis. RESULTS: Six related literatures
      were found to meet the requirements. According to heterogeneity results, there
      was no significant difference in homozygous types(P>0.05), while there was
      significant difference in two others types (P all<0.05). For wild CYP1A1MspI
      homozygous for the reference group, Combined OR of heterozygous mutation,
      homozygous, heterozygous + homozygous mutation in AL and control groups were
      1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1MspI
      homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL)
      and the control group were 0.10 and 0.76 respectively, Z values in non-acute
      lymphoblastic leukemia and control group were 0.74 and 0.75. CONCLUSION: There is
      no correlation between CYP1A1MspI gene polymorphism and the susceptibility of
      childhood AL.

PMID- 22365407
TI  - Orthogonal test design for optimization of the extraction of flavonid from the
      Fructus Gardeniae.
AB  - OBJECTIVE: It is imperative to provide some consistent experimental results for
      the extraction of flavonid from Fructus Gardeniae. METHODS: The key extraction
      parameters that influenced the yield of flavonid from Fructus Gardeniae were
      optimized by employing an orthogonal experiment [L(9)(3)(4)], including the ratio
      of buffer solution (Na(2)B(4)O(7).10H(2)O) to raw material, concentration of
      Fructus Gardeniae in extracting solution, extraction time and pH of buffer
      solution. An UV/Vis detector was used to perform the qualitative and quantitative
      analyses of the extracted flavonid with the using of the standard sample.
      RESULTS: The maximum extraction yield of the crude extract was 5.0533 (mg/g)
      after 20 min when the mass ratio of Na(2)B(4)O(7).10H(2)O to raw material was
      0.4%, the concentration of Fructus Gardeniae in the extraction solution was 1/12
      (g/mL), and pH of buffer solution was 4.5. The positive reactions to the Molish
      and HCl-Mg tests suggested that the extracted compound was flavonoid, and FTIR
      measurements also identified the presence of flavonoid in the extracts.
      CONCLUSION: This work is expected to provide a basis for further research,
      development, and utilization of Fructus gardenia in flavonid extraction.

PMID- 22365408
TI  - A Flavobacterium lindanitolerans strain isolated from the ascites sample of a
      Chinese patient with EV71 virus infection.
AB  - A strain of Flavobacterium lindanitolerans isolated from a sick child's ascites
      was described. The 16S rRNA gene of the strain was 100% identical to that of
      Flavobacterium lindanitolerans which was first identified in India in 2008. It
      was first described that the isolate required X factor (Hemin) for growth in the
      optimal conditions of 37  degrees C with 5% CO(2). The isolate produced indole
      and H(2)S. It did not present hemolytic feature on blood agar.

PMID- 22365409
TI  - Computer-assisted rational design, synthesis, and bioassay of non-steroidal anti
      inflammatory agents.
AB  - A focused dataset of previously synthesized and tested [1,2,4]-triazolo[1,5
      a]pyridines and pyridine-3-carboxylates was studied by Molecular Field Topology
      Analysis (MFTA) to identify steric and electronic determinants of anti
      inflammatory activity useful for the design and synthesis of new anti
      inflammatory agents. Rational design based on the MFTA model identified eleven
      novel pyridine-3-carboxylates (2a-e and 3a-f) as promising. After synthesis and
      screening, three of (2a, 2c, 3a) revealed potent anti-inflammatory activity
      exceeding that of indomethacin, the reference inhibitor for artificially induced
      edema in rats.

PMID- 22365410
TI  - Synthesis and preliminary antibacterial evaluation of Linezolid-like 1,2,4
      oxadiazole derivatives.
AB  - In the present study the synthesis of new Linezolid-like molecules has been
      achieved by substitution of the oxazolidinone central heterocyclic moiety with a
      1,2,4-oxadiazole ring. Two series of 1,2,4-oxadiazoles, bearing different side
      chains and containing a varying number of fluorine atoms, were synthesized and
      preliminarily tested for biological activity against some Gram-positive and Gram
      negative bacteria using Linezolid and Ceftriaxone as reference drugs.

PMID- 22365411
TI  - Novel triacsin C analogs as potential antivirals against rotavirus infections.
AB  - Recently our group has demonstrated that cellular triglyceride (TG) levels play
      an important role in rotavirus replication. In this study, we further examined
      the roles of the key enzymes for TG synthesis (lipogenesis) in the replication of
      rotaviruses by using inhibitors of fatty acid synthase, long chain fatty acid
      acyl-CoA synthetase (ACSL), and diacylglycerol acyltransferase and acyl
      CoA:cholesterol acyltransferase in association with lipid droplets of which TG is
      a major component. Triacsin C, a natural ACSL inhibitor from Streptomyces
      aureofaciens, was found to be highly effective against rotavirus replication.
      Thus, novel triacsin C analogs were synthesized and evaluated for their
      efficacies against the replication of rotaviruses in cells. Many of the analogs
      significantly reduced rotavirus replication, and one analog (1e) was highly
      effective at a nanomolar concentration range (ED(50) 0.1MUM) with a high
      therapeutic index in cell culture. Our results suggest a crucial role of lipid
      metabolism in rotavirus replication, and triacsin C and/or its analogs as
      potential therapeutic options for rotavirus infections.

PMID- 22365412
TI  - Synthesis and photodynamic properties of adamantylethoxy Zn(II) phthalocyanine
      derivatives in different media and in human red blood cells.
AB  - Novel unsymmetrically substituted Zn(II) phthalocyanine bearing an
      adamantylethoxy group (AZnPc) was synthesized by the ring expansion reaction of
      boron(III) subphthalocyanine chloride with an appropriated phthalonitrile
      derivative (APc). Also, APc was used to obtain a new Zn(II) phthalocyanine
      bearing four adamantylethoxy groups (A(4)ZnPc) by cyclotetramerization reaction.
      The spectroscopic and photodynamic properties of these photosensitizers were
      compared with those of a Zn(II) phthalocyanine substituted by four methoxy groups
      (M(4)ZnPc) in different media. Similar results were obtained in N,N
      dimethylformamide. However, a higher photodynamic activity was found for AZnPc in
      a biomimetic system formed by reverse micelles. This behavior was also observed
      in the presence of human red blood (HRB) cells, which were used as an in vitro
      cellular model. Thus, AZnPc was the most effective photosensitizer to produce HRB
      cells hemolysis. The photodynamic effect produced a decrease in the HRB cells
      osmotic stability leading to the release of hemoglobin. Studies of photodynamic
      action mechanism showed that photohemolysis of HRB cells was protected in the
      presence of azide ion, while the addition of mannitol produced a negligible
      effect on the cellular photodamage, indicating the intermediacy of
      O(2)((1)Delta(g)). Therefore, the presence of an adamantyl unit in the
      phthalocyanine macrocycle represents an interesting molecular architecture for
      potential phototherapeutic agents.

PMID- 22365413
TI  - [Surgery for bronchiectasis].
AB  - The incidence of bronchiectasis has declined significantly in industrialized
      countries and its management has also changed because of the progress of
      antibiotic therapy. However, for some patients, medical treatment is not
      sufficient to control the disease and the quality of life is affected. Surgical
      treatment is then a very good alternative, when a gesture of complete resection
      of the affected areas is feasible in terms of lung function and it allows, with a
      low morbidity and mortality, for very satisfactory long-term results and slows
      down the progression of the disease. In cases of diffuse and inhomogeneous
      bronchiectasis, a gesture of incomplete resection of cystic, non-perfused and
      suppurative areas improves symptoms and reduces recurrent infections. When the
      bronchiectasis is diffuse, but homogeneous, associated with severe respiratory
      failure, lung transplantation should be considered. Therefore, surgery remains
      important in the management of bronchiectasis. Its indications and the lung
      resection gesture to achieve should be discussed based on the symptoms, imaging
      examinations and the lung function of the patient.

PMID- 22365414
TI  - Synthesis of nanoscale zero-valent iron/ordered mesoporous carbon for adsorption
      and synergistic reduction of nitrobenzene.
AB  - Nanoscale zero-valent iron (NZVI) supported on ordered mesoporous carbon (OMC)
      was synthesized through liquid phase reduction route. The NZVI/OMC composite was
      characterized by X-ray diffraction, N(2) adsorption/desorption and transmission
      electron microscopy. Results reveal that the composite possesses ordered
      mesostructure with NZVI distributing homogeneously on the surface of OMC support.
      The removal effects of nitrobenzene (NB) in water with OMC, NZVI/OMC and non
      supported NZVI were evaluated. Results indicate that NZVI/OMC shows enhanced
      removal efficiency, which is attributed to its adsorption and synergistic
      reduction for NB. The transformation process of NB was further investigated by
      HPLC. Nitrosobenzene and phenylhydroxylamine were detected as intermediate
      products and aniline was the final reductive product.

PMID- 22365415
TI  - Amber codon-mediated expanded saturation mutagenesis of proteins using a cell
      free translation system.
AB  - Saturation mutagenesis of proteins, in which an amino acid at a specific site is
      substituted with each of the other 19 amino acids, is a powerful method for
      protein analysis and engineering. However, 19 mutated genes have to be prepared
      to express all possible amino acid-substituted proteins at one site. We
      previously reported a four-base codon-mediated saturation mutagenesis method for
      the expression of all 20 amino acid-substituted proteins from one four-base codon
      containing gene using 20 types of chemically aminoacylated tRNAs corresponding to
      the four-base codon. In this study, an improved method for saturation mutagenesis
      using an amber codon was developed. By combining the use of Escherichia coli
      derived amber suppressor tRNAs and chemically aminoacylated Mycoplasma-derived
      tRNAs, all 20 mutated proteins were successfully expressed from one amber mutant
      gene in a cell-free translation system. The use of E. coli-derived amber
      suppressor tRNAs simplified the preparation of the tRNA reagents required for
      saturation mutagenesis, and also improved the expression of some of the mutated
      proteins. The expressed mutant proteins were used to evaluate the effect of the
      amino acid substitutions on the ligand-binding activity. To further expand the
      possibilities of saturation mutagenesis, a series of nonnatural amino acids
      analogous to a naturally occurring amino acid was added to the amino acid
      repertoire. The expanded saturation mutagenesis was utilized to evaluate the
      effect of a series of atomic-level side chain substitutions on the protein
      activity.

PMID- 22365416
TI  - Postmastectomy radiotherapy with integrated scar boost using helical tomotherapy.
AB  - The purpose of this study was to evaluate helical tomotherapy dosimetry in
      postmastectomy patients undergoing treatment for chest wall and positive nodal
      regions with simultaneous integrated boost (SIB) in the scar region using strip
      bolus. Six postmastectomy patients were scanned with a 5-mm-thick strip bolus
      covering the scar planning target volume (PTV) plus 2-cm margin. For all 6 cases,
      the chest wall received a total cumulative dose of 49.3-50.4 Gy with daily
      fraction size of 1.7-2.0 Gy. Total dose to the scar PTV was prescribed to 58.0
      60.2 Gy at 2.0-2.5 Gy per fraction. The supraclavicular PTV and mammary nodal PTV
      received 1.7-1.9 dose per fraction. Two plans (with and without bolus) were
      generated for all 6 cases. To generate no-bolus plans, strip bolus was contoured
      and overrode to air density before planning. The setup reproducibility and
      delivered dose accuracy were evaluated for all 6 cases. Dose-volume histograms
      were used to evaluate dose-volume coverage of targets and critical structures. We
      observed reduced air cavities with the strip bolus setup compared with what we
      normally see with the full bolus. The thermoluminescence dosimeters (TLD) in vivo
      dosimetry confirmed accurate dose delivery beneath the bolus. The verification
      plans performed on the first day megavoltage computed tomography (MVCT) image
      verified that the daily setup and overall dose delivery was within 2% accuracy
      compared with the planned dose. The hotspot of the scar PTV in no-bolus plans was
      111.4% of the prescribed dose averaged over 6 cases compared with 106.6% with
      strip bolus. With a strip bolus only covering the postmastectomy scar region, we
      observed increased dose uniformity to the scar PTV, higher setup reproducibility,
      and accurate dose delivered beneath the bolus. This study demonstrates the
      feasibility of using a strip bolus over the scar using tomotherapy for SIB
      dosimetry in postmastectomy treatments.

PMID- 22365417
TI  - An evaluation of the contouring abilities of medical dosimetry students for the
      anatomy of a prostate cancer patient.
AB  - Prostate cancer is one of the most common diseases treated in a radiation
      oncology department. One of the major predictors of the treatment outcome and
      patient side effects is the accuracy of the anatomical contours for the treatment
      plan. Therefore, the purpose of this study was to determine which anatomical
      structures are most often contoured correctly and incorrectly by medical
      dosimetry students. The author also wanted to discover whether a review of the
      contouring rules would increase contouring accuracy. To achieve this, a male
      computed tomography dataset consisting of 72 transverse slices was sent to
      students for contouring. The students were instructed to import this dataset into
      their treatment planning system and contour the following structures: skin,
      bladder, rectum, prostate, penile bulb, seminal vesicles, left femoral head, and
      right femoral head. Upon completion of the contours, the contour file was
      evaluated against a "gold standard" contour set using StructSure software
      (Standard Imaging, Inc). A review of the initial contour results was conducted
      and then students were instructed to contour the dataset a second time. The
      results of this study showed significant differences between contouring sessions.
      These results and the standardization of contouring rules should benefit all
      individuals who participate in the treatment planning of cancer patients.

PMID- 22365418
TI  - The use of RapidArc volumetric-modulated arc therapy to deliver stereotactic
      radiosurgery and stereotactic body radiotherapy to intracranial and extracranial
      targets.
AB  - Twenty-three targets in 16 patients treated with stereotactic radiosurgery (SRS)
      or stereotactic body radiotherapy (SBRT) were analyzed in terms of dosimetric
      homogeneity, target conformity, organ-at-risk (OAR) sparing, monitor unit (MU)
      usage, and beam-on time per fraction using RapidArc volumetric-modulated arc
      therapy (VMAT) vs. multifield sliding-window intensity-modulated radiation
      therapy (IMRT). Patients underwent computed tomography simulation with site
      specific immobilization. Magnetic resonance imaging fusion and optical tracking
      were incorporated as clinically indicated. Treatment planning was performed using
      Eclipse v8.6 to generate sliding-window IMRT and 1-arc and 2-arc RapidArc plans.
      Dosimetric parameters used for target analysis were RTOG conformity index
      (CI(RTOG)), homogeneity index (HI(RTOG)), inverse Paddick Conformity Index (PCI),
      D(mean) and D5-D95. OAR sparing was analyzed in terms of D(max) and D(mean).
      Treatment delivery was evaluated based on measured beam-on times delivered on a
      Varian Trilogy linear accelerator and recorded MU values. Dosimetric conformity,
      homogeneity, and OAR sparing were comparable between IMRT, 1-arc RapidArc and 2
      arc RapidArc plans. Mean beam-on times +/- SD for IMRT and 1-arc and 2-arc
      treatments were 10.5 +/- 7.3, 2.6 +/- 1.6, and 3.0 +/- 1.1 minutes, respectively.
      Mean MUs were 3041, 1774, and 1676 for IMRT, 1-, and 2-arc plans, respectively.
      Although dosimetric conformity, homogeneity, and OAR sparing were similar between
      these techniques, SRS and SBRT fractions treated with RapidArc were delivered
      with substantially less beam-on time and fewer MUs than IMRT. The rapid delivery
      of SRS and SBRT with RapidArc improved workflow on the linac with these otherwise
      time-consuming treatments and limited the potential for intrafraction organ and
      patient motion, which can cause significant dosimetric errors. These clinically
      important advantages make image-guided RapidArc useful in the delivery of SRS and
      SBRT to intracranial and extracranial targets.

PMID- 22365419
TI  - The Schizosaccharomyces pombe AlkB homolog Abh1 exhibits AP lyase activity but no
      demethylase activity.
AB  - 2-Oxoglutarate (2OG) and iron (Fe(II)) dependent dioxygenases catalyze a wide
      range of biological oxidations, including hydroxylation and demethylation of
      proteins and nucleic acids. AlkB from Escherichia coli directly reverses certain
      methyl lesions in DNA, and defines a subfamily of 2OG/Fe(II) dioxygenases that
      has so far been shown to be involved in both nucleic acid repair and
      modification. The human genome encodes nine AlkB homologs and the function of
      most of these is still unknown. The fission yeast Schizosaccharomyces pombe has
      two AlkB homologs and here we have addressed the function of one of these, Abh1,
      which appears not to possess a classical AlkB-like repair activity. No enzymatic
      activity was found toward methylated DNA or etheno adducts, nor was the yeast
      abh1- mutant sensitive toward alkylating agents. Interestingly, heterologous
      expression of E. coli AlkB protected the fission yeast cells from alkylation
      induced cytotoxicity, suggesting that S. pombe lacks systems for efficient repair
      of lesions that are AlkB substrates. Further, we show that Abh1 possesses an
      unexpected DNA incision activity at apurinic/apyrimidinic (AP) sites. This AP
      lyase activity did not depend on 2OG and Fe(II) and was not repressed by
      dioxygenase inhibitors. Survival and complementation analyses failed to reveal
      any biological role for AP lyase cleavage by Abh1. It appears that in vitro AP
      lyase activity can be detected for a number of enzymes belonging to structurally
      and functionally unrelated families, but the in vivo significance of such
      activities may be questionable.

PMID- 22365420
TI  - Functional analysis of the interaction between the mismatch repair protein MutS
      and the replication processivity factor beta clamp in Pseudomonas aeruginosa.
AB  - Interaction between MutS and the replication factor beta clamp has been
      extensively studied in a Mismatch Repair context; however, its functional
      consequences are not well understood. We have analyzed the role of the MutS-beta
      clamp interaction in Pseudomonas aeruginosa by characterizing a beta clamp
      binding motif mutant, denominated MutSbeta, which does not interact with the
      replication factor. A detailed characterization of P. aeruginosa strain PAO1
      harboring a chromosomal mutSbeta allele demonstrated that this mutant strain
      exhibited mutation rates to rifampicin and ciprofloxacin resistance comparable to
      that of the parental strain. mutSbeta PAO1 was as proficient as the parental
      strain for DNA repair under highly mutagenic conditions imposed by the adenine
      base analog 2-aminopurine. In addition, using a tetracycline resistance reversion
      assay to assess the repair of a frameshift mutation, we determined that the
      parental and mutSbeta strains exhibited similar reversion rates. Our results
      clearly indicate that the MutS-beta clamp interaction does not have a central
      role in the methylation-independent Mismatch Repair of P. aeruginosa.

PMID- 22365421
TI  - Evaluation of socket healing in irradiated rats after diode laser exposure
      (histological and morphometric studies).
AB  - OBJECTIVE: The purpose of this study is to evaluate the effect of low-level laser
      therapy (LLLT) in enhancing bone repair in irradiated sockets of albino rats.
      DESIGN: Thirty male Swiss Albino rats ranging from 120 to 150 g were used in this
      study. The animals were subjected 6 gray gamma radiations. Three days post
      irradiation, right and left mandibular first molars were extracted. The sockets
      of the left sides were irradiated by (GaAIAs) diode laser device immediately
      after extraction, while the sockets of the right side were not exposed to the
      laser and served as control. The rats were randomly assigned into three groups
      (10 rats each) according to the date of sacrifice, 3, 7 and 10 days into groups
      I, II and III, respectively. The two sides of each mandible were separated. Each
      group was further subdivided into subgroups A and B (10 specimens each), where A
      represents the right side of the mandible and B represents the left side. The
      specimens were stained with hematoxylin and eosin, and Masson's trichrome.
      RESULTS: LLLT accelerated bone healing, while, radiotherapy induced delay of bone
      healing along the three experimental groups. This acceleration was assessed
      histologically by the presence of mature collagen fibre bundles and early new
      bone formation in the lased groups. Histomorphometric analysis revealed an
      increase in the area percentage of bone trabeculae in the lased sockets compared
      to the control ones in group II. This increase was statistically significant (p =
      0.0274). The increase in the area percentage of bone trabeculae between the lased
      and control sockets of group III was statistically insignificant (p = 0.1903).
      CONCLUSIONS: In a rat model application of LLLT with a GaAIAs diode laser device
      can enhance bone healing and mineralisation in sockets subjected to gamma
      radiation.

PMID- 22365422
TI  - Dowsing can be interfered with by radio frequency radiation.
AB  - The soil radiation, watercourses and ores have been located for centuries by
      sensitive persons, dowsers. An ideomotoric explanation of the dowsing reaction,
      with no physical interaction, has been accepted. Our present re-analyses of some
      such results have shown, that there could be a physical phenomenon connecting the
      human reactions in field experiments, where the test subjects walked or were
      sitting in a slow-moving car, with the windows covered, and a dowsing rod in
      their hands was recorded. The correlations between the reaction points by test
      subjects in the moving car and the points by walking along the same path were
      highly significant. The correlation was not seen in all test locations. The
      distance between the test location and the radio tower, and the incidence angle
      of the transmitted radio wave, possibly had an effect on results. We hypothesize
      that the experiments carried out in the 20th century were interfered with by man
      made radio frequency radiation, mainly FM radio and TV broadcasting, as test
      subjects' bodies absorbed the radio waves and unconscious hand movement reactions
      took place following the standing waves or intensity variations due to multipath
      propagation.

PMID- 22365423
TI  - 3-dimensional aortic annular assessment by multidetector computed tomography
      predicts moderate or severe paravalvular regurgitation after transcatheter aortic
      valve replacement: a multicenter retrospective analysis.
AB  - OBJECTIVES: This study sought to analyze multidetector computed tomography (MDCT)
      3-dimensional aortic annular dimensions for the prediction of paravalvular aortic
      regurgitation (PAR) following transcatheter aortic valve replacement (TAVR).
      BACKGROUND: Moderate or severe PAR after TAVR is associated with increased
      morbidity and mortality. METHODS: A total of 109 consecutive patients underwent
      MDCT pre-TAVR with a balloon expandable aortic valve. Differences between
      transcatheter heart valve (THV) size and MDCT measures of annular size (mean
      diameter, area, and circumference) were analyzed concerning prediction of PAR.
      Patients with THV malposition (n = 7) were excluded. In 50 patients, MDCT was
      repeated after TAVR to assess THV eccentricity (1 - short diameter/long diameter)
      and expansion (MDCT measured THV area/nominal THV area). RESULTS: Moderate or
      severe PAR (13 of 102) was associated with THV undersizing (THV diameter - mean
      diameter = -0.7 +/- 1.4 mm vs. 0.9 +/- 1.8 mm for trivial to mild PAR, p < 0.01).
      The difference between THV size and MDCT annular size was predictive of PAR (mean
      diameter: area under the curve [AUC]: 0.81, 95% confidence interval [CI]: 0.68 to
      0.88; area: AUC: 0.80, 95% CI: 0.65 to 0.90; circumference: AUC: 0.76, 95% CI:
      0.59 to 0.91). Annular eccentricity was not associated with PAR (AUC: 0.58, 95%
      CI: 0.46 to 0.75). We found that 35.3% (36 of 102) and 45.1% (46 of 102) of THVs
      were undersized relative to the MDCT mean diameter and area, respectively. THV
      oversizing relative to the annular area was not associated with THV eccentricity
      or underexpansion (oversized vs. undersized THVs; expansion: 102.7 +/- 5.3% vs.
      106.1 +/- 5.6%, p = 0.03; eccentricity: median: 1.7% [interquartile range: 1.4%
      to 3.0%] vs. 1.7% [interquartile range: 1.1% to 2.7%], p = 0.28). CONCLUSIONS:
      MDCT-derived 3-dimensional aortic annular measurements are predictive of moderate
      or severe PAR following TAVR. Oversizing of THVs may reduce the risk of moderate
      or severe PAR.

PMID- 22365424
TI  - Cross-sectional computed tomographic assessment improves accuracy of aortic
      annular sizing for transcatheter aortic valve replacement and reduces the
      incidence of paravalvular aortic regurgitation.
AB  - OBJECTIVES: In an effort to define the gold standard for annular sizing for
      transcatheter aortic valve replacement (TAVR), we sought to critically analyze
      and compare the predictive value of multiple measures of the aortic annulus for
      post-TAVR paravalvular (PV) regurgitation and then assess the impact of a novel
      cross-sectional computed tomographic (CT) approach to annular sizing. BACKGROUND:
      Recent studies have shown clear discrepancies between conventional 2-dimensional
      (2D) echocardiographic and CT measurements. In terms of aortic annular
      measurement for TAVR, such findings have lacked the outcome analysis required to
      inform clinical practice. METHODS: The discriminatory value of multiple CT
      annular measures for post-TAVR PV aortic regurgitation was compared with 2D
      echocardiographic measures. TAVR outcomes with device selection according to
      aortic annular sizing using a traditional 2D transesophageal echocardiography
      guided or a novel CT-guided approach were also studied. RESULTS: In receiver
      operating characteristic models, cross-sectional CT parameters had the highest
      discriminatory value for post-TAVR PV regurgitation: This was with the area under
      the curve for [maximal cross-sectional diameter minus prosthesis size] of 0.82
      (95% confidence interval: 0.69 to 0.94; p < 0.001) and that for [circumference
      derived cross-sectional diameter minus prosthesis size] of 0.81 (95% confidence
      interval: 0.7 to 0.94; p < 0.001). In contrast, traditional echocardiographic
      measures were nondiscriminatory in relation to post-TAVR PV aortic regurgitation.
      The prospective application of a CT-guided annular sizing approach resulted in
      less PV aortic regurgitation of grade worse than mild after TAVR (7.5% vs. 21.9%;
      p = 0.045). CONCLUSIONS: Our data lend strong support to 3-dimensional cross
      sectional measures, using CT as the new gold standard for aortic annular
      evaluation for TAVR with the Edwards SAPIEN device.

PMID- 22365425
TI  - Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality
      and incomplete recovery.
AB  - OBJECTIVES: This study sought to evaluate the long-term mortality in patients
      with viral myocarditis, and to establish the prognostic value of various
      clinical, functional, and cardiovascular magnetic resonance (CMR) parameters.
      BACKGROUND: Long-term mortality of viral myocarditis, as well as potential risk
      factors for poor clinical outcome, are widely unknown. METHODS: A total of 222
      consecutive patients with biopsy-proven viral myocarditis and CMR were enrolled.
      A total of 203 patients were available for clinical follow-up, and 77 patients
      underwent additional follow-up CMR. The median follow-up was 4.7 years. Primary
      endpoints were all-cause mortality and cardiac mortality. RESULTS: We found a
      relevant long-term mortality in myocarditis patients (19.2% all cause, 15%
      cardiac, and 9.9% sudden cardiac death [SCD]). The presence of late gadolinium
      enhancement (LGE) yields a hazard ratio of 8.4 for all-cause mortality and 12.8
      for cardiac mortality, independent of clinical symptoms. This is superior to
      parameters like left ventricular (LV) ejection fraction, LV end-diastolic volume,
      or New York Heart Association (NYHA) functional class, yielding hazard ratios
      between 1.0 and 3.2 for all-cause mortality and between 1.0 and 2.2 for cardiac
      mortality. No patient without LGE experienced SCD, even if the LV was enlarged
      and impaired. When focusing on the subgroup undergoing follow-up CMR, we found an
      initial NYHA functional class >I as the best independent predictor for incomplete
      recovery (p = 0.03). CONCLUSIONS: Among our population with a wide range of
      clinical symptoms, biopsy-proven viral myocarditis is associated with a long-term
      mortality of up to 19.2% in 4.7 years. In addition, the presence of LGE is the
      best independent predictor of all-cause mortality and of cardiac mortality.
      Furthermore, initial presentation with heart failure may be a good predictor of
      incomplete long-term recovery.

PMID- 22365426
TI  - Postprandial accumulation of chylomicrons and chylomicron remnants is determined
      by the clearance capacity.
AB  - OBJECTIVE: To better understand the postprandial clearance of triglyceride-rich
      lipoproteins (TRLs) and its relation to the fasting kinetics of TRLs. METHODS:
      Two studies were performed on 30 male subjects: a fasting kinetic study to
      determine the fasting secretion and clearance rates of apolipoprotein B (apoB)
      100 and triglycerides in the very low-density lipoprotein 1 and 2 (VLDL(1) and
      VLDL(2)) fractions; and a postprandial study to determine the postprandial
      accumulation of apoB48, apoB100 and triglycerides in the chylomicron, VLDL(1) and
      VLDL(2) fractions. Results from these two studies were combined to characterize
      the postprandial clearance of TRLs in a physiologically relevant setting.
      RESULTS: Our results show that postprandial accumulation of the apoB48-carrying
      chylomicrons can be predicted from the clearance capacity of the lipolytic
      pathway, determined in the fasting state. Furthermore, we show that chylomicrons
      and VLDL(1) particles are not cleared equally by the lipoprotein lipase pathway,
      and that chylomicrons seem to be the preferred substrate. Subjects with a rapid
      fasting lipid metabolism accumulate lower levels of postprandial triglycerides
      with less accumulation of apoB100 in the VLDL(1) fraction and a faster transfer
      of apoB100 into the VLDL(2) fraction. In contrast, fasting VLDL(1) secretion does
      not predict postprandial triglyceride accumulation. CONCLUSIONS: Non-fasting
      triglyceride levels have recently been identified as a major predictor of future
      cardiovascular events. Here we show that the capacity of the lipolytic pathway is
      a common determinant of both the fasting and non-fasting triglyceride levels and
      may thus play an important role in the development of dyslipemia and
      atherosclerosis.

PMID- 22365428
TI  - Computer-aided manufacturing in medicine.

PMID- 22365427
TI  - A comparison of maxillofacial CBCT and medical CT.

PMID- 22365429
TI  - Virtual technologies in dentoalveolar evaluation and surgery.

PMID- 22365430
TI  - Computer-guided planning and placement of dental implants.

PMID- 22365431
TI  - Technological advances in the treatment of facial trauma.

PMID- 22365432
TI  - Digital technologies in mandibular pathology and reconstruction.

PMID- 22365433
TI  - Computer-aided orthognathic surgery.

PMID- 22365434
TI  - Facial skeletal augmentation using custom facial implants.

PMID- 22365435
TI  - Systematic treatment planning protocol for patients with maxillofacial defects:
      avoiding living a life of seclusion and depression.

PMID- 22365436
TI  - Digital technologies in oral and maxillofacial surgery. Preface.

PMID- 22365437
TI  - Variceal transection of esophageal varix using the ESD method: new treatment
      technique for esophageal varix (with video).

PMID- 22365438
TI  - Gastric necrosis caused by gastric banding.

PMID- 22365439
TI  - Mediastinal abscess formation after EUS-guided FNA: are patients with sarcoidosis
      at increased risk?

PMID- 22365440
TI  - A case of oropharyngeal squamous papilloma in which endoscopic resection was
      performed.

PMID- 22365441
TI  - Effect of the introducer technique compared with the pull technique on the
      peristomal infection rate in PEG: a meta-analysis.
AB  - BACKGROUND: Peristomal infection is a main complication of PEG. The pull
      technique appears to be associated with higher infection rates compared with the
      introducer technique, although published results are controversial. OBJECTIVE: To
      determine which technique is associated with a higher risk of infection. DESIGN:
      Systematic review and meta-analysis. SETTING: Studies reporting rates of
      peristomal infection after PEG performed by either the pull or introducer
      technique. PATIENTS: This study involved 2336 patients from 6 comparative and 10
      observational studies. INTERVENTION: Public MEDLINE (National Library of Medicine
      journal articles database), Excerpta Medica Database, Cochrane Central Register
      of Controlled Trials, and Latin American and Caribbean Center on Health Sciences
      Information databases and proceedings of two meetings, Digestive Disease Week and
      United European Gastroenterology Week, were searched. Both comparative and
      observational studies were included and analyzed separately. MAIN OUTCOME
      MEASUREMENTS: Effect measures from each comparative study were reported as the
      odds ratio (OR). The pooled effect was then calculated. The infection rate in
      each observational study was also calculated, and a summary effect was then
      determined. RESULTS: In comparative studies, the risk of infection was
      significantly higher with the pull technique (OR 13.0; 95% confidence interval
      [CI], 4.6-36.8; P < .0001). Similarly, observational studies also reported higher
      infection rates with the pull technique (10.7%; 95% CI, 4.9-21.8 with the pull
      technique vs 0.9%; 95% CI, 0.2-4.5 with the introducer technique). LIMITATIONS:
      Few studies were available for inclusion, and there was a high risk of bias among
      the comparative studies. CONCLUSION: The pull technique appears to be associated
      with a significantly higher risk of infection compared with the introducer
      technique.

PMID- 22365442
TI  - Medical expulsive therapy in a tertiary care emergency department.
AB  - OBJECTIVE: To assess the extent of Medical expulsive therapy (MET) use and
      practice patterns in our tertiary care emergency department. MET is the first
      line intervention for select symptomatic urolithiasis recommended by the American
      Urological Association and supported by clinical trials investigating its
      efficacy. Nonetheless, MET is not always prescribed in the emergency department
      setting for symptomatic patients with ureteral stones. METHODS: Using the
      "International Classification of Diseases" diagnostic codes, we retrospectively
      reviewed the medical records of all emergency department patients treated for
      urolithiasis at our institution from January to December 2008. Abstracted patient
      data included demographic and medically relevant information; MET use was
      determined by reviewing the electronic prescriptions at discharge. RESULTS: Of
      165 patients identified with a diagnosis of renal colic owing to urolithiasis, 23
      were excluded for suspected stone passage or failure to document a stone on cross
      sectional imaging. Most (138 [97%] of 142) of the remaining patients met the
      criteria for outpatient treatment of symptomatic stone episodes and were eligible
      for MET. Urology consultation was requested in 19 outpatients (13%), and MET was
      prescribed for most (14 [73.7%] of 19). Of the 119 patients seen by an emergency
      department physician without urologic input and discharged, 17 (14%) received
      MET. Overall, tamsulosin was prescribed to 31 (22%) of 138 stone episodes treated
      with an outpatient trial of passage. CONCLUSION: The underusage of tamsulosin in
      the emergency department of our institution highlights the need for educational
      interventions to improve the quality and cost of emergent patient care.

PMID- 22365444
TI  - Penile plication without degloving enables effective correction of complex
      Peyronie's deformities.
AB  - OBJECTIVE: To present our initial experience with extended plication repair for
      men with severe and/or biplanar penile curvature. MATERIALS AND METHODS: A review
      of men who underwent plication repair for complex penile deformity (biplanar
      curvature or curvature >= 60 degrees ) was performed. All patients underwent
      tunical plication via a 2-cm penoscrotal incision mobilized distally along the
      penile shaft without degloving. Angle of curvature, direction(s), stretched
      penile length (SPL), and number of sutures were recorded. RESULTS: Among 102
      patients treated with plication surgery, 43 (44%) had complex penile deformity.
      Among 11 men with biplanar curvature, median angle in the primary plane of
      curvature was corrected from 45 degrees  to 10 degrees  and secondary plane was
      corrected from 35 degrees  to 5 degrees  using an average of 7 sutures (5 degrees
      correction per suture). Among 32 men with severe curvature, median angle of
      curvature was corrected from 70 degrees  to 15 degrees  using an average of 11
      sutures (6 degrees  correction per suture). SPL was unchanged in 29 (69%),
      increased an average of 0.65 cm in 7 (16%), and decreased 0.5 cm in only 6 (14%)
      patients. At a mean follow-up of 15.3 months, repeat plication was required in 2
      patients and 2 required penile prosthesis. CONCLUSION: Penile plication without
      degloving appears to be safe and effective for correction of complex penile
      curvature without significant impact on penile length.

PMID- 22365445
TI  - A method for the rapid detection of urinary tract infections.
AB  - OBJECTIVE: To determine the reliability of a rapid detection method compared with
      the reference standard streaked agar plate in diagnosing the presence of urinary
      tract infection (UTI). METHODS: De-identified clean catch urine specimens from
      980 office visit patients were processed during a 30-day period. Classic 1-MUL
      and 10-MUL streaked agar plates were used in parallel with the new CultureStat
      Rapid UTI Detection System (CSRUDS). Urine results were evaluated using the
      CSRUDS at 30 and 90 minutes after collection. A comparative analysis of the
      subsequent plate results versus the CSRUDS results was achieved for 973 of these
      samples. RESULTS: Positive UTI conditions were accurately identified by both
      CSRUDS and agar streak plate methods. CSRUDS accurately identified UTI negative
      conditions with 99.3% reliability at 90 minutes. The negative predictive value of
      CSRUDS was 99.2% at 30 minutes. CONCLUSION: Current agar plating for first-round
      UTI screening has substantial documented problems that can negatively affect an
      accurate and timely UTI diagnosis. A novel rapid detection system, the CSRUDS
      provides UTI negative/positive same-day results in <= 90 minutes from the start
      of test. Such rapidly available results will enable more accurate and timely
      clinical decisions to be made in the urology office, particularly regarding
      infection status before urologic instrumentation.

PMID- 22365446
TI  - Editorial comment.

PMID- 22365447
TI  - A modified surgical technique for treatment of radiation-induced vesicovaginal
      fistulas.
AB  - OBJECTIVE: To present a modified surgical technique in the management of
      radiation-induced vesicovaginal fistulas. Radiation-induced vesicovaginal
      fistulas pose a great challenge to the treating surgeon owing to the fibrotic,
      poorly vascularized tissue in the area. Various techniques have been used to
      promote healing and prevent fistula recurrence, but most centers still recommend
      urinary diversion or more individualized management. MATERIALS AND METHODS: We
      used the left rectus abdominis muscle based on the deep inferior epigastric
      vessels as an interposition flap in 3 patients presenting with vesicovaginal
      fistulas 19, 28, and 34 years after radiotherapy for cervical cancer. The
      fistulas were isolated using an abdominal approach, and the distal half of the
      left rectus abdominis muscle was mobilized. Without closure of the 2 defects, the
      muscle was then interposed between the bladder and vagina, where it was fixed
      using single sutures around the edges of the 2 defects. The operations were
      performed by a team that included both a urologist and a plastic surgeon.
      RESULTS: All 3 patients underwent successful treatment. With a follow-up of 5-8
      years, there has been no recurrence of symptoms. CONCLUSION: This modified
      surgical technique offers well-vascularized, nonirradiated tissue to be used as
      an interposition flap based on the inferior epigastric vessels in the management
      of radiation-induced vesicovaginal fistulas. The technique allows obstruction of
      the fistula without the need for closure of the mucosal defects in the bladder
      and vagina.

PMID- 22365448
TI  - Pediatric renal lymphangiectasia: importance of recognition and accurate renal
      imaging.
AB  - Renal lymphangiectasia is a rare diagnosis. It is also referred to as renal
      lymphangioma, renal lymphangiomatosis, peripelvic lymphangiectasia, renal
      peripelvic multicystic lymphangiectasia, and hygroma renale. The presentation
      varies, and the diagnosis depends on accurate radiologic interpretation. We
      present the radiologic images of a pediatric patient who was diagnosed with renal
      lymphangiectasia after being evaluated for suspected nonaccidental trauma to
      emphasize the importance of identifying this entity by the characteristic
      radiologic findings.

PMID- 22365449
TI  - Editorial comment.

PMID- 22365451
TI  - Dyssynergia or asynergia?

PMID- 22365450
TI  - Doppler ultrasound-guided percutaneous nephrolithotomy with two-step tract
      dilation for management of complex renal stones.
AB  - OBJECTIVE: To report our experience and assess the safety and efficacy of Doppler
      ultrasound-guided percutaneous nephrolithotomy (PCNL) with 2-step tract dilation
      for complex renal stones. MATERIALS AND METHODS: From March 2009 to February
      2011, 262 patients underwent PCNL. Eighty-three patients had a complete and 105
      had partial staghorn calculus, and 74 had a renal pelvic stone of >2 cm in
      diameter. Thirty-five patients had renal surgical history. Doppler ultrasound
      guided PCNL with 2-step tract dilation were performed. Stones were fragmented and
      cleared using a combination of ultrasonic and pneumatic lithotripters. RESULTS:
      All PCNL procedures were successful. Successful access to the collecting system
      was 100%. Although most of the cases (231/262) were managed satisfactorily by a
      single tract, a second tract was used in 31 cases. Mean operation time was 56
      minutes (range 25-145). The primary stone-free rate of PCNL was 80.9%. There were
      39 auxiliary procedures (13 second PCNL and 26 extracorporeal shock wave
      lithotripsy). One month after treatment, the overall stone-free rate was 92.7%.
      Five patients (1.9%) received blood transfusion. Eight patients (3.1%) with a
      postoperative fever of >=38.5 degrees C were cured by intravenous antibiotics. No
      other severe complications occurred. The mean postoperative stay was 3.8 days
      (range 2-12). CONCLUSION: Doppler ultrasound-guided PCNL with 2-step tract
      dilation for complex renal stones is safe, effective, and worthy of wider use in
      clinical practice.

PMID- 22365452
TI  - Hydroxyfasudil ameliorates bladder dysfunction in male spontaneously hypertensive
      rats.
AB  - OBJECTIVE: To investigate the effect of hydroxyfasudil, a nonselective Rho-kinase
      inhibitor, on hypertension-related bladder dysfunction in spontaneously
      hypertensive rats (SHRs), as there is an increasing evidence that the Rho
      associated protein kinase (ROCK) system plays an important role in bladder
      contraction. METHODS: Twelve-week-old male SHRs were treated with hydroxyfasudil
      (1 mg/kg i.p.) once a day for 6 weeks. Wistar rats and SHRs without treatment
      with hydroxyfasudil were used as controls. Six weeks after the hydroxyfasudil
      treatment, voiding functions were evaluated by metabolic cages and cystometric
      studies under urethane anesthesia (1.0 g/kg i.p.). Bladder blood flow (BBF) was
      estimated by the hydrogen clearance method. The bladder tissue levels of nerve
      growth factor (NGF) and ROCK activity were evaluated by the ELISA method.
      RESULTS: The SHR showed significant increases in micturition frequency and
      decreases in single-voided volume in metabolic cages, and significantly increases
      in micturition frequency and intercontractile interval in cystometric studies.
      Furthermore, the SHR showed significant increases in the BBF and bladder NGF
      concentration compared with the Wistar rats. These alterations in the SHR were
      significantly ameliorated after treatment with hydroxyfasudil, with small changes
      in blood pressure. However, the maximum detrusor pressures during voiding and the
      ROCK activities in the experimental bladders were similar in all rats examined.
      CONCLUSION: Our data indicate that this dose of hydroxyfasudil was effective on
      the BBF, whereas it had no significant effect on micturition pressure. These
      findings suggest that hydroxyfasudil could ameliorate hypertension-related
      bladder dysfunction in the SHR via improvement of the BBF (248 words).

PMID- 22365453
TI  - The contemporary role of lymph node dissection during nephroureterectomy in the
      management of upper urinary tract urothelial carcinoma: the Canadian experience.
AB  - OBJECTIVE: To investigate the association between lymph node dissection (LND) and
      survival among patients undergoing nephroureterectomy for upper urinary tract
      urothelial cell carcinoma (UTUC). METHODS: This study includes 1029 patients from
      10 Canadian institutions who underwent nephroureterectomy between 1990 and 2010.
      Disease-specific survival (DSS), overall survival (OS), and recurrence-free
      survival (RFS) were compared for patients with a node-negative LND (N0), node
      positive LND (N+), or no LND (Nx) using Kaplan-Meyer analysis and Cox regression
      analysis. The association between survival and number of positive nodes, number
      of nodes removed, and ratio of positive nodes to nodes removed was also
      investigated. RESULTS: The median follow-up for the entire cohort was 19.8 months
      (interquartile range = 7.2-53.8). LND was performed in 276 (26.8%) patients, and
      77 (27.9%) had N+ disease. Patients with N+ disease had significantly shorter OS,
      DSS, and RFS compared with N0 and Nx patients(P < .01). No differences were
      identified between N0 and Nx patients in any survival categories (P > .05). A
      ratio of positive nodes to nodes removed >= 20% had a per annum hazard ratio of
      2.24 (95% confidence interval [CI] 1.18-4.65) for OS, 2.70 (95% CI = 1.25-5.83)
      for DSS, and 1.94 (95% CI = 1.13-3.32) for RFS. The number of positive nodes and
      the number of nodes removed were not associated with survival in any survival
      category (P > .05). CONCLUSION: LND during nephroureterectomy provides more
      accurate staging and prediction of survival; however, it remains uncertain
      whether LND independently improves survival in patients with UTUC.

PMID- 22365455
TI  - Live surgical demonstrations: an old, but increasingly controversial practice.
AB  - OBJECTIVE: To survey a group of leading academic urologists from North America
      and abroad about their opinions regarding the educational value, safety, and
      ethics of live surgical demonstrations. MATERIALS AND METHODS: An anonymous
      survey pertaining to live clinical demonstrations was sent to all active members
      of the American Association of Genitourinary Surgeons (AAGUS). RESULTS: Ninety
      (50%) members completed the survey. Most respondents had performed at least one
      live surgical demonstration (93.2% at away institution, 81.5% at home
      institution). Overall anxiety level as a visiting professor was rated as
      moderate, high, and very high by 29.8%, 25.0%, and 17.9% of respondents,
      respectively. Anxiety while performing demonstrations at one's home institution
      was reported as moderate, high, and very high by 28.2%, 9.9%, and 8.5% of
      respondents, respectively. Excessive conversation in the operating room was cited
      as a major distraction by 41.3% of respondents. Concern over the appropriateness
      of selected cases was reported often (43.9%) and always (13.4%) of the time. Only
      28.2% of AAGUS members would let a visiting faculty member operate on them or a
      family member. Most (70.9%) respondents felt live surgical demonstrations are
      morally ethical, but only 30.1% stated they should continue indefinitely in their
      present form. CONCLUSION: No studies have been published within the urological
      literature about live operative demonstrations. Results from the present survey
      support concerns within the cardiothoracic and endoscopy literature about the
      continued use of live operative demonstrations. A formal review culminating in
      the development of an explicit policy statement by urologists should be
      undertaken.

PMID- 22365456
TI  - Editorial "Algae innovation".

PMID- 22365457
TI  - In this issue/abstract thinking: of mice, monkeys, and men.

PMID- 22365458
TI  - Facing autism: eye tracking paves the way to underlying mechanisms.

PMID- 22365459
TI  - Amygdala response to emotional faces: a neural marker of risk for bipolar
      disorder?

PMID- 22365460
TI  - Parsing heterogeneity in autism spectrum disorders: visual scanning of dynamic
      social scenes in school-aged children.
AB  - OBJECTIVE: To examine patterns of variability in social visual engagement and
      their relationship to standardized measures of social disability in a
      heterogeneous sample of school-aged children with autism spectrum disorders
      (ASD). METHOD: Eye-tracking measures of visual fixation during free-viewing of
      dynamic social scenes were obtained for 109 children with ASD (mean age, 10.2 +/-
      3.2 years), 37 of whom were matched with 26 typically-developing (TD) children
      (mean age, 9.5 +/- 2.2 years) on gender, age, and IQ. The smaller subset allowed
      between-group comparisons, whereas the larger group was used for within-group
      examinations of ASD heterogeneity. RESULTS: Between-group comparisons revealed
      significantly attenuated orientation to socially salient aspects of the scenes,
      with the largest effect size (Cohen's d = 1.5) obtained for reduced fixation on
      faces. Within-group analyses revealed a robust association between higher
      fixation on the inanimate environment and greater social disability. However, the
      associations between fixation on the eyes and mouth and social adaptation varied
      greatly, even reversing, when comparing different cognitive profile subgroups.
      CONCLUSIONS: Although patterns of social visual engagement with naturalistic
      social stimuli are profoundly altered in children with ASD, the social adaptivity
      of these behaviors varies for different groups of children. This variation likely
      represents different patterns of adaptation and maladaptation that should be
      traced longitudinally to the first years of life, before complex interactions
      between early predispositions and compensatory learning take place. We propose
      that variability in these early mechanisms of socialization may serve as proximal
      behavioral manifestations of genetic vulnerabilities.

PMID- 22365461
TI  - Autism spectrum disorder and autistic traits in the Avon Longitudinal Study of
      Parents and Children: precursors and early signs.
AB  - OBJECTIVE: To chart the emergence of precursors and early signs of autism
      spectrum disorder (ASD) and autistic traits in the Avon Longitudinal Study of
      Parents and Children, a prospective longitudinal cohort study of the surviving
      offspring of 14,541 pregnant women from southwestern England with an expected
      delivery date between April 1991 and December 1992. METHOD: Parents'
      contemporaneous reports of their infant's development (241 questionnaire
      responses collected up to 30 months of age) were examined in relation to the
      diagnosis of autism spectrum disorder by age 11 years (n = 86) and a measure of
      autistic traits, derived by factor analysis. RESULTS: Among the children later
      diagnosed with ASD, concerns about vision and hearing were more often reported in
      the first year, and differences in social, communication, and fine motor skills
      were evident from 6 months of age. Repetitive behaviors and differences in play,
      imitation, and feeding habits were reported in the second year. Differences in
      temperament emerged at 24 months of age and bowel habit by 30 months. All of
      these early signs were strongly associated with the presence of autistic traits
      in the rest of the population and these differences were often evident in the
      first year of development. Over the first 30 months of development, the best
      predictors of both later ASD and autistic traits included the Social Achievement
      and Communication scores from the Denver Developmental Screening Test, measures
      of communicative skills (Vocabulary and Combines Words) from the MacArthur Infant
      Communicative Development Inventories, and a repetitive behavior score.
      CONCLUSIONS: Precursors, early signs, and other developmental differences were
      reported in the first year of development among children from the general
      population who later developed autism spectrum disorder and subtler autistic
      traits. Other differences emerged and unfolded as development progressed. The
      findings confirm the long-held suspicion that early differences underscore the
      multifaceted nature of autism spectrum disorder and the broader autism phenotype,
      and highlight the centrality of impairments in social communication skills.

PMID- 22365462
TI  - A randomized controlled trial of the Cool Teens CD-ROM computerized program for
      adolescent anxiety.
AB  - OBJECTIVE: Computerized cognitive behavioral interventions for anxiety disorders
      in adults have been shown to be efficacious, but limited data are available on
      the use of computerized interventions with young persons. Adolescents in
      particular are difficult to engage in treatment and may be especially suited to
      computerized technologies. This paper describes the results of a small randomized
      controlled trial of the Cool Teens program for adolescent anxiety, and examines
      potential barriers to treatment and user preferences of computerized technology
      in this population. METHOD: Forty-three adolescents with a primary diagnosis of
      anxiety were randomly allocated to the Cool Teens program, a 12-week computerized
      cognitive-behavioral therapy program for anxiety management, or a 12-week wait
      list. Effects on symptoms, negative thoughts, and life interference were assessed
      at post-treatment and 3-month follow-up, based on diagnosis as well as self and
      maternal report. RESULTS: Using mixed-model analyses, at post-treatment and
      follow-up assessments, adolescents in the Cool Teens condition, compared with
      those on the wait list, were found to have significant reductions in the total
      number of anxiety disorders, the severity of the primary anxiety disorder, and
      the average severity for all disorders. These results were matched by significant
      reductions in mother and child questionnaire reports of anxiety, internalizing
      symptoms, automatic thoughts, and life interference. Further few barriers to
      treatment were found, and user preferences indicated that the computerized
      treatment was well suited to adolescents with anxiety. CONCLUSIONS: The Cool
      Teens program is efficacious for treatment of adolescent anxiety. Clinical trial
      registration information-A randomized controlled trial of the Cool Teens
      computerized program for anxious adolescents compared with waist list;
      http://www.anzctr.org.au; ACTRN12611000508976.

PMID- 22365463
TI  - Involvement in bullying and suicide-related behavior at 11 years: a prospective
      birth cohort study.
AB  - OBJECTIVE: To study the prospective link between involvement in bullying (bully,
      victim, bully/victim), and subsequent suicide ideation and suicidal/self
      injurious behavior, in preadolescent children in the United Kingdom. METHOD: A
      total of 6,043 children in the Avon Longitudinal Study of Parents and Children
      (ALSPAC) cohort were assessed to ascertain involvement in bullying between 4 and
      10 years and suicide related behavior at 11.7 years. RESULTS: Peer victimization
      (victim, bully/victim) was significantly associated with suicide ideation and
      suicidal/self-injurious behavior after adjusting for confounders. Bully/victims
      were at heightened risk for suicide ideation (odds ratio [OR]; 95% confidence
      interval [CI]): child report at 8 years (OR = 2.84; CI = 1.81-4.45); child report
      at 10 years (OR = 3.20; CI = 2.07-4.95); mother report (OR = 2.71; CI = 1.81
      4.05); teacher report (OR = 2.79; CI = 1.62-4.81), as were chronic victims: child
      report (OR = 3.26; CI = 2.24-4.75); mother report (OR = 2.49; CI = 1.64-3.79);
      teacher report (OR = 5.99; CI = 2.79-12.88). Similarly, bully/victims were at
      heightened risk for suicidal/self-injurious behavior: child report at 8 years (OR
      = 2.67; CI = 1.66-4.29); child report at 10 years (OR = 3.34; CI = 2.17-5.15);
      mother report (OR = 2.09; CI = CI = 1.36-3.20); teacher report (OR = 2.44, CI =
      1.39-4.30); as were chronic victims: child report (OR = 4.10; CI = 2.76-6.08);
      mother report (OR = 1.91; 1.22-2.99); teacher report (OR = 3.26; CI = 1.38-7.68).
      Pure bullies had increased risk of suicide ideation according to child report at
      age 8 years (OR = 3.60; CI = 1.46-8.84), suicidal/self-injurious behavior
      according to child report at age 8 years (OR = 3.02; CI = 1.14-8.02), and teacher
      report (OR = 1.84; CI = 1.09-3.10). CONCLUSIONS: Children involved in bullying,
      in any role, and especially bully/victims and chronic victims, are at increased
      risk for suicide ideation and suicidal/self-injurious behavior in preadolescence.

PMID- 22365464
TI  - Aftercare, emergency department visits, and readmission in adolescents.
AB  - OBJECTIVE: U.S. and Canadian data demonstrate decreasing inpatient days,
      increasing nonurgent emergency department (ED) visits, and short supply of child
      psychiatrists. Our study aims to determine whether aftercare reduces ED visits
      and/or readmission in adolescents with first psychiatric hospitalization. METHOD:
      We conducted a population-based cohort analysis using linked health
      administrative databases with accrual from April 1, 2002, to March 1, 2004. The
      study cohort included all 15- to 19-year-old adolescents with first psychiatric
      admission. Adolescents with and without aftercare in the month post-discharge
      were matched on their propensity to receive aftercare. Our primary outcome was
      time to first psychiatric ED visit or readmission. Secondary outcomes were time
      to first psychiatric ED visit and readmission, separately. RESULTS: We identified
      4,472 adolescents with first-time psychiatric admission. Of these, 57% had
      aftercare in the month post-discharge. Propensity-score-based matching, which
      accounted for each individual's propensity for aftercare, produced a cohort of
      3,004 adolescents. In matched analyses, relative to those with no aftercare in
      the month post-discharge, those with aftercare had increased likelihood of
      combined outcome (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.05
      1.42), and readmission (HR = 1.38, 95% CI = 1.14-1.66), but not ED visits (HR =
      1.14, 95% CI = 0.95-1.37). CONCLUSIONS: Our results are provocative: we found
      that aftercare in the month post-discharge increased the likelihood of
      readmission but not ED visit. Over and above confounding by severity and
      Canadian/U.S. systems differences, our results may indicate a relative lack of
      psychiatric services for youth. Our results point to the need for improved data
      capture of pediatric mental health service use.

PMID- 22365465
TI  - Amygdala hyperactivation during face emotion processing in unaffected youth at
      risk for bipolar disorder.
AB  - OBJECTIVE: Youth at familial risk for bipolar disorder (BD) show deficits in face
      emotion processing, but the neural correlates of these deficits have not been
      examined. This preliminary study tests the hypothesis that, relative to healthy
      comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those
      with a first-degree BD relative) will demonstrate amygdala hyperactivation when
      viewing fearful and happy faces. The at-risk youth were unaffected, in that they
      had no history of mood disorder. METHOD: Amygdala activity was examined in 101
      unrelated participants, 8 to 18 years old. Age, gender, and IQ-matched groups
      included BD (N = 32), unaffected at-risk (N = 13), and HC (N = 56). During
      functional magnetic resonance imaging, participants attended to emotional and
      nonemotional aspects of fearful and happy faces. RESULTS: While rating their fear
      of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala
      hyperactivity versus HC. There were no between-group differences in amygdala
      activity in response to happy faces. Post-hoc comparisons revealed that, in at
      risk youth, familial risk status (offspring versus sibling), presence of Axis I
      diagnosis (n = 1 attention-deficit/hyperactivity disorder [ADHD], n = 1 social
      phobia), and history of medication exposure (n = 1) did not influence imaging
      findings. CONCLUSIONS: We found amygdala hyperactivation in both unaffected at
      risk and BD youth while rating their fear of fearful faces. These pilot data
      suggest that both face emotion labeling deficits and amygdala hyperactivity
      during face processing should receive further study as potential BD
      endophenotypes. Longitudinal studies should test whether amygdala hyperactivity
      to fearful faces predicts conversion to BD in at-risk youth.

PMID- 22365467
TI  - Mental health in low-to-moderate risk preterm, low birth weight, and small for
      gestational age children at 4 to 5 years: the role of early maternal parenting.
AB  - OBJECTIVES: The majority of children born preterm, with low birth weight, or
      small for gestational age are born with low-to-moderate risk (LTM), yet most
      research focuses on the high-risk group. Little is known about whether children
      with LTM perinatal risk are at greater risk for mental health problems, or what
      the role of early maternal parenting is in determining these outcomes. METHOD:
      Longitudinal data were from a large nationally representative Australian cohort
      of 5,000 children, aged 0 to 1, 2 to 3, and 4 to 5 years of age. Participants
      were 354 children with LTM perinatal risk born at 33 to 36 weeks, with birth
      weight 1,501 to 2,499 grams, or born between the first and 10th percentiles for
      gestational age; and 2,461 children in the normal birth weight, term comparison
      group. Child mental health was measured by mother-report on the Strengths and
      Difficulties Questionnaire (SDQ). Parenting irritability, warmth, self-efficacy,
      maternal separation anxiety, and overprotective parenting were measured when
      children were 0 to 1 and 2 to 3 years of age. RESULTS: Parents in the LTM
      perinatal risk group were more likely to experience parenting difficulties on one
      of eight parenting measures (irritable parenting at age 0-1 year) when adjusting
      for socio-demographic differences (odds ratio = 1.43; 95% confidence interval =
      1.05, 1.95, p < .02). This group difference was no longer apparent by age 2 to 3
      years. Compared with healthy-term peers, there were small increases in Emotional
      Symptoms and Total Difficulties on the SDQ for the LTM perinatal risk group at
      age 4 to 5 years. When accounting for maternal-specific and socio-demographic
      factors, LTM perinatal risk group continued to predict Emotional Symptoms but not
      Total Difficulties at age 4 to 5 years. CONCLUSIONS: Children with LTM perinatal
      risk were at a small increased risk for emotional difficulties but did not differ
      significantly from other children of similar social backgrounds in their risk for
      generalized mental health problems. These findings support a biological and socio
      economic, rather than parenting, pathway to psychological risk in children born
      with LTM perinatal risk.

PMID- 22365466
TI  - Stress reactivity and corticolimbic response to emotional faces in adolescents.
AB  - OBJECTIVE: Adolescence is a critical period in the development of lifelong
      patterns of responding to stress. Understanding underpinnings of variations in
      stress reactivity in adolescents is important, as adolescents with altered stress
      reactivity are vulnerable to negative risk-taking behaviors including substance
      use, and have increased lifelong risk for psychopathology. Although both
      endocrinological and corticolimbic neural system mechanisms are implicated in the
      development of stress reactivity patterns, the roles of these systems and
      interactions between the systems in reactivity to social stimuli in adolescents
      are not clear. We investigated the relationship between cortisol response to a
      laboratory-based social stressor and regional brain responses to emotional face
      stimuli in adolescents. METHOD: Changes in cortisol levels following the Trier
      Social Stress Test-Child version (TSST-C) were measured in 23 disadvantaged and
      chronically stressed adolescents who also participated in functional magnetic
      resonance imaging during processing of emotional faces and structural magnetic
      resonance imaging. The relationships between changes in cortisol following the
      TSST-C with regional brain activation during face processing, as well as with
      regional brain morphology, were assessed. RESULTS: Cortisol change on the TSST-C
      showed a significant inverse relationship with left hippocampus response to
      fearful faces (p < .05, corrected); significant associations with volume were not
      observed. CONCLUSIONS: Increased cortisol response to the Trier social stressor
      was associated with diminished response of the left hippocampus to faces
      depicting fear. This suggests that HPA-corticolimbic system mechanisms may
      underlie vulnerability to maladaptive responses to stress in adolescents that may
      contribute to development of stress-related disorders.

PMID- 22365468
TI  - Cardiovascular events and methylphenidate use in Taiwan.

PMID- 22365471
TI  - [Lyme disease with hepatitis and corticosteroids: a case report].
AB  - INTRODUCTION: Abnormalities of liver function tests have been occasionally
      described in large series of Lyme disease, but only one case of hepatitis
      directly related to infection have been described in literature. CASE REPORT: A
      78-year-old-man, with a past medical history of polymyalgia rheumatica (PMR) who
      had discontinued corticosteroids two years before, presented a transient acute
      fever and liver cholestasis and cytolysis after an exposure to tick bites. A few
      days later, cervical pain occurred and corticosteroids were resumed as a PMR
      relapse was suspected. Hematogenous dissemination with acute meningoradiculitis
      and multiple erythema migrans led to conclude to a stage 2 Lyme disease.
      CONCLUSION: Although hepatitis complicating the course of Lyme disease has been
      described in literature, the marked inflammation in our patient led us to
      investigate the possibility of a co-infection. Also, we discuss the
      responsibility of corticosteroids in clinical worsening of Lyme disease if they
      are prescribed without concomitant antibiotics.

PMID- 22365472
TI  - [Chorea, lupus and antiphospholipid antibodies].
AB  - Chorea may occur in patients with SLE with a frequency estimated at 1 to 3% in
      adults and up to 9% in paediatric lupus. Chorea is frequently a presenting
      feature, and is strongly related to the presence of antiphospholipid antibodies.
      A treatment with antiplatelet agents and hydroxychloroquine is generally
      sufficient. During follow-up, the patients with chorea have a significant higher
      risk to develop thrombotic events (mainly arterial). They also have an excess
      risk of obstetric morbidity and valvular disease. The prescription of
      antiplatelet agents and adequate management, especially during pregnancy, can
      probably reduce this risk.

PMID- 22365473
TI  - [Auditory and vestibular findings in Fabry disease: a study of 25 patients].
AB  - PURPOSE: Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage
      disorder due to deficient activity of the enzyme alpha-galactosidase A. Males and
      females exhibit severe organ involvement. The high incidence of otological
      symptoms was recently reported. PATIENTS AND METHODS: Monocentric and
      retrospective study of twenty-five patients with FD (13 families; seven males and
      18 females). The patients underwent audiological assessment before initiation and
      during enzyme replacement therapy. We also analysed neurologic heart and kidney
      status. RESULTS: Twenty patients (80%; 13 females and seven males) complained of
      otologic symptoms. Audiological evaluation showed a sensorineural hearing loss in
      17 patients, bilateral in 16 out of them. Vestibular examination showed a
      functional impairment in two patients (one female, one male). Correlations were
      found between hearing loss and either kidney disease (73,3%), neurological
      complications (100%) and cardiomyopathy (80%). Fourteen patients (56%; seven
      females, seven males) received enzyme replacement therapy. Improvement or
      stabilization of the audiological evaluation was reported in seven patients,
      whereas worsening was observed in three patients. CONCLUSION: This study confirms
      the high frequency of audiological involvements in females and males with FD. Our
      analysis suggests that the frequency of hearing loss is increased in the presence
      of renal or neurologic involvement or cardiomyopathy. There is no clinically
      significant efficacy of enzyme replacement therapy on hearing function. Although
      the pathophysiology remains unknown, a vascular mechanism responsible of the
      inner ear involvement seems to be privileged.

PMID- 22365474
TI  - [Detection of extended spectrum beta-lactamase OXA-141 in Pseudomonas aeruginosa
      strains isolated from patients with cystic fibrosis].
AB  - INTRODUCTION: The aims of this research were to study the presence of extended
      spectrum beta-lactamases (ESBL) to investigate the location of the genes encoding
      these enzymes, and determine the clonal relationship of strains of ceftazidime
      resistant Pseudomonas aeruginosa isolated from Mexican patients with cystic
      fibrosis. METHODS: We determined the resistance profile to 11 antibiotics (CLSI)
      and phenotypic ESBL detection following a disk diffusion method adapted for P.
      aeruginosa. Characterization of ESBL genes and integrons was performed by
      polymerase chain reaction (PCR) and DNA sequencing, while analysis of the clonal
      relationship was performed by pulsed field gel electrophoresis (PFGE). RESULTS:
      Of the 148 strains studied, 22 were resistant to ceftazidime, and analysis by PCR
      and sequencing revealed the presence of the gene bla(OXA-141) in 7 strains, 6 of
      which were resistant and one, susceptible to ceftazidime. In addition, bla(GES)
      was detected in 11 strains. intI2 and intI3 genes were not detected by PCR, but
      in the 6 ceftazidime-resistant strains, the bla(OXA-141) gene was determined in a
      class 1 integron. Analysis of the clonal relationship of isolates showed that the
      majority of patients were infected during the study period with P. aeruginosa
      strains that exhibit different patterns, especially in individuals without a
      familial relationship. CONCLUSIONS: This report demonstrates the existence of the
      bla(OXA-141) gene associated with a class 1 integron in several strains of P.
      aeruginosa, as well as bla(GES) genes, and their location and variants are being
      studied by our research group. This, combined with the diversity of strains able
      to infect several susceptible individuals, suggests the risk of spread of P.
      aeruginosa-strain ESBL producers among Mexican populations with cystic fibrosis.

PMID- 22365475
TI  - Assessment of pulmonary restriction in cervical spinal cord injury: a preliminary
      report.
AB  - OBJECTIVE: To compare the prevalence of pulmonary restriction on the basis of a
      vital capacity (VC) below the lower limit of normal (LLN) and a normal or high
      forced expiratory volume in 1 second (FEV(1))/VC ratio with the criterion
      standard of total lung capacity (TLC) less than LLN in individuals with spinal
      cord injury (SCI) and able-bodied (AB) controls. DESIGN: Method comparison with
      criterion standard. SETTING: University research center. PARTICIPANTS:
      Individuals with cervical SCI (n=12; injury level, C5-7) and AB controls (n=12)
      matched for age, stature, and body mass. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: TLC via plethysmography; FEV(1) and VC via spirometry; and maximum
      inspiratory and expiratory pressures (P(Imax) and P(Emax)). RESULTS: All
      participants with SCI exhibited a VC less than LLN and a normal-to-high FEV(1)/VC
      ratio, whereas significantly fewer (8 of 12) participants with SCI exhibited a
      TLC less than LLN (P=.046). For the AB group, no participant exhibited a VC or
      TLC less than LLN. Percent-predicted VC was lower than the percent-predicted TLC
      in SCI (P=.013), whereas percent-predicted VC was higher than percent-predicted
      TLC in AB controls (P=.001). Percent-predicted P(Imax) was higher than P(Emax) in
      SCI (P=.001) but not AB controls (P=.146). CONCLUSIONS: A VC less than LLN with a
      normal-to-high FEV(1)/VC ratio does not accurately predict pulmonary restriction
      in cervical SCI. When using spirometry to infer pulmonary restriction in cervical
      SCI, we recommend using a VC below 60% of the AB predicted value.

PMID- 22365476
TI  - Comparison of pelvic complex kinematics during treadmill and overground walking.
AB  - OBJECTIVES: To determine if there are changes in temporal gait parameters with a
      focus on pelvis when comparing overground and treadmill ambulation, and to assess
      the effect of sex. DESIGN: An observational study employing motion analysis
      techniques to evaluate pelvic movement during gait. SETTING: University
      biomechanics laboratory. PARTICIPANTS: Men (n=8; 22.5+/-3.0 y) and women (n=6;
      23.8+/-4.1 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cadence,
      stride time, stance phase percent, and pelvic tilt, obliquity, and rotation
      parameters throughout the gait cycle were assessed during overground and
      treadmill walking. Kinematic data were recorded using a passive full body marker
      based motion analysis system. While an independent sample t test was used to
      determine if differences in walking speed were evident between sexes, a 2-way,
      repeated-measures analysis of variance was performed to examine the effect of
      walking mode and sex on each dependent variable. RESULTS: Significant differences
      (P<.05) between overground and treadmill walking for the temporal parameters
      analyzed were evident for both sexes. A lower pelvic obliquity motion for
      treadmill walking when compared with overground walking was evident for both
      sexes, and the pelvic rotation movement pattern showed the greatest difference
      between walking modes. The majority of the significant differences between sexes
      were of a magnitude greater than the differences between overground and treadmill
      walking. CONCLUSIONS: The differences in temporal and angular kinematics
      identified in the present study should be considered when treadmills are used in
      a rehabilitation program.

PMID- 22365477
TI  - The Posttraumatic Stress Disorder Checklist as a screening measure for
      posttraumatic stress disorder in rehabilitation after burn injuries.
AB  - OBJECTIVES: To determine the profile of posttraumatic stress disorder (PTSD)
      among outpatients with burn injuries referred to psychology in a rehabilitation
      hospital, and the utility of the Posttraumatic Stress Disorder Checklist-Civilian
      Version (PCL-C) as a screening measure for PTSD. DESIGN: Retrospective
      psychological chart review. SETTING: Outpatient burn clinic of a rehabilitation
      hospital. PARTICIPANTS: Outpatients (N=132) with burns referred to psychology
      between December 1999 and January 2010. INTERVENTIONS: Psychological evaluation
      and self-report questionnaires measuring PTSD and depression. MAIN OUTCOME
      MEASURES: The Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition to assess clinical diagnosis of disorders, PCL-C to measure PTSD, and the
      Beck Depression Inventory-II to measure depression. RESULTS: Of 132 outpatients,
      127 (96%) had work-related injuries, 116 (88%) were men, and 16 (12%) were women.
      Mean age +/- SD at injury was 39.0+/-11.1 years. Mean time from injury to
      assessment was 15.7+/-42.7 months. Burn etiology included: electrical (46.2%),
      scald (28.0%), flame (16.7%), chemical (5.3%), and contact (3.8%). Most patients
      (75%) were diagnosed with PTSD, either clinical (39.4%) or subclinical (35.6%).
      PTSD (clinical or subclinical) was frequently diagnosed in the following etiology
      groups: scald (85.7%), flame (77.3%), and electrical (74.6%). There were
      significant relationships between PTSD and depression (P<.001), and between
      subclinical PTSD and adjustment disorder (P<.03). PCL-C mean scores +/- SD in the
      clinical and subclinical PTSD groups were 59.7+/-8.9 and 43.5+/-15.6,
      respectively. A PCL-C total score of 50 or higher had a sensitivity of 90% and
      specificity of 79% for PTSD diagnosis. CONCLUSIONS: There was a high prevalence
      of PTSD (clinical or subclinical) among outpatients with burns referred to
      psychology. Prospective screening of psychological symptoms, clinical assessment,
      and intervention is warranted, especially for patients with work-related burn
      injuries. Our results suggest that PCL-C is a useful screening measure for PTSD
      in patients with burns.

PMID- 22365478
TI  - A meta-analysis of botulinum toxin sphincteric injections in the treatment of
      incomplete voiding after spinal cord injury.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis to examine the effect
      of injecting botulinum toxin A (BTX-A) into the detrusor sphincter on improving
      bladder emptying in individuals with spinal cord injury (SCI). DATA SOURCES:
      MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for all relevant
      articles published from 1980 to September 2011. DATA SELECTION: All trials
      examining the use of BTX-A injections into the detrusor sphincter for the
      treatment for incomplete bladder emptying after SCI were included if at least 50%
      of the study sample comprised subjects with SCI, and if the SCI sample size was 3
      or greater. DATA EXTRACTION: A standardized mean difference (SMD) +/- SE and 95%
      confidence interval (CI) were calculated for each outcome of interest, and the
      results were pooled using a fixed or random effects model, as appropriate.
      Outcomes assessed included postvoid residual urine volume (PRV), detrusor
      pressure (PDet), and urethral pressure (UP). Effect sizes were interpreted as
      small, 0.2; moderate, 0.5; and large, 0.8. DATA SYNTHESIS: A relatively limited
      number of studies (2 randomized controlled trials, 6 uncontrolled trials) were
      identified. The 8 studies included results from 129 subjects. There was a
      statistically significant decrease in PRV at 1 month (SMD=1.119+/-.140; 95% CI,
      .844-1.394; P<.001), with a pooled mean PRV decrease from 251.8 to 153.0 mL.
      There was a moderate statistical effect on PDet (SMD=.570+/-.217; 95% CI, .145
      .995; P=.009); pooled PDet decreased from 88.7 to 20.5 cmH(2)O. A large
      statistical effect size on UP (SMD=.896+/-.291; 95% CI, .327-1.466; P=.002) and
      an improvement from 119.7 to 102.3 cmH(2)O were seen. The systematic review also
      indicated a 50% reduction in urinary tract infections based on 3 studies.
      Discontinuation or reduction in catheter usage was reported in 4 studies after
      BTX-A. CONCLUSIONS: Results of the meta-analysis indicate that BTX-A is effective
      in reducing PRV and demonstrating a statistically significant reduction in PDet
      and UP 1 month postinjection. However, the clinical utility of BTX-A is yet to be
      determined.

PMID- 22365479
TI  - Manual wheelchair skills capacity versus performance.
AB  - OBJECTIVES: To test the hypotheses that self-reported manual wheelchair skills
      capacity and performance are highly correlated and that capacity significantly
      exceeds performance. DESIGN: Cross-sectional. SETTING: Rehabilitation center.
      PARTICIPANTS: Manual wheelchair users (N=26) with a variety of diagnoses and an
      average of 10.8 years of wheelchair experience. INTERVENTIONS: None. MAIN OUTCOME
      MEASURE: We administered the questionnaire version of the Wheelchair Skills Test
      version 4.1 (WST-Q), recording the participants' capacity and performance scores
      on each of 32 skills. RESULTS: The mean total WST-Q capacity and performance
      scores +/- SD were 72.5%+/-19.2% and 58.1%+/-21.2%. The Spearman rho correlation
      coefficient between total WST-Q capacity and performance scores was .853
      (P=.000). The mean difference +/- SD in total WST-Q scores (capacity minus
      performance) was 14.4%+/-9.5% with a median of 10.9% (P=.000 on a Wilcoxon signed
      rank test). There were 9 (28%) of the 32 skills for which the participants' mean
      capacity success rates were >=20% higher than the mean performance success rates.
      Of the reasons for not performing individual skills, 66% of the instances were
      because the participant lacked the capacity. A variety of other reasons were
      given by participants for not performing skills of which they were capable (eg,
      the situation was not encountered, it could be avoided, or assistance was usually
      available). CONCLUSIONS: Manual wheelchair skills capacity and performance are
      highly correlated but capacity exceeds performance, more so for some skills than
      others. Although further study is needed, these findings have implications for
      the assessment and training of wheelchair skills.

PMID- 22365480
TI  - Motor imagery ability in patients with traumatic brain injury.
AB  - OBJECTIVE: To assess motor imagery (MI) ability in patients with moderate to
      severe traumatic brain injury (TBI). DESIGN: Prospective, cohort study. SETTING:
      University hospital rehabilitation unit. PARTICIPANTS: Patients with traumatic
      brain injury (mean coma duration, 18d) undergoing rehabilitation (n=20) and
      healthy controls (n=17) matched for age and education level. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The vividness of MI was assessed using a
      revised version of the Movement Imagery Questionnaire-Revised second version (MIQ
      RS); the temporal features were assessed using the time-dependent motor imagery
      (TDMI) screening test, the temporal congruence test, and a walking trajectory
      imagery test; and the accuracy of MI was assessed using a mental rotation test.
      RESULTS: The MIQ-RS revealed a decrease of MI vividness in the TBI group. An
      increasing number of stepping movements was observed with increasing time periods
      in both groups during the TDMI screening test. The TBI group performed a
      significantly smaller number of imagery movements in the same movement time. The
      temporal congruence test revealed a significant correlation between imagery and
      actual stepping time in both groups. The walking trajectory test revealed an
      increase of the imagery and actual walking time with increasing path length in
      both groups, but the ratio of imaginary walking over actual walking time was
      significantly greater than 1 in the TBI group. Results of the hand mental
      rotation test indicated significant effects of rotation angles on imagery
      movement times in both groups, but rotation time was significantly slower in the
      TBI group. CONCLUSIONS: Our patients with TBI demonstrated a relatively preserved
      MI ability indicating that MI could be used to aid rehabilitation and subsequent
      functional recovery.

PMID- 22365481
TI  - Preoperative home-based physical therapy versus usual care to improve functional
      health of frail older adults scheduled for elective total hip arthroplasty: a
      pilot randomized controlled trial.
AB  - OBJECTIVE: To investigate the feasibility and preliminary effectiveness of a home
      based intensive exercise program to improve physical health of frail elderly
      patients scheduled for elective total hip arthroplasty (THA). DESIGN: Single
      blind pilot randomized controlled trial. SETTING: Patients' homes and a general
      hospital in The Netherlands. PARTICIPANTS: Frail patients (N=30) older than 65
      years. INTERVENTION: A preoperative, home-based program supervised by an
      experienced physical therapist to train functional activities and walking
      capacity. The control group received usual care consisting of 1 session of
      instructions. MAIN OUTCOME MEASURES: Feasibility was determined on the basis of
      adherence to treatment, patient satisfaction, adverse events, walking distance
      (measured with a pedometer), and intensity of exercise (evaluated with the Borg
      scale). Preliminary pre- and postoperative effectiveness was determined by the
      Timed Up & Go (TUG) test, 6-minute walk test (6MWT), Chair Rise Time, and self
      reported measures of functions, activities, and participation. RESULTS: Patient
      satisfaction and adherence to the training were good (median=5 on a 5-point
      Likert scale) and no serious adverse events occurred. The Borg score during
      training was 14 (range, 13-16). Preoperative clinical relevant differences on the
      TUG test (2.9 s; 95% confidence interval [CI], -0.9 to 6.6) and significant
      differences on the 6MWT (41 m; 95% CI, 8 to 74) were found between groups.
      CONCLUSIONS: Intensive preoperative training at home is feasible for frail
      elderly patients waiting for THA and produces relevant changes in functional
      health. A larger multicenter randomized controlled trial is in progress to
      investigate the (cost-)effectiveness of preoperative training.

PMID- 22365482
TI  - Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in
      depressive disorder.
AB  - Depression and eating disorders are frequently associated, but the molecular
      pathways responsible for co-occurrence of altered mood, appetite and body weight
      are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and
      orexigenic properties and low central NPY levels have been reported in major
      depression. In the present study, we hypothesized that in patients with major
      depression alteration of mood, appetite and body weight may be related to NPY
      reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma
      levels and affinities of NPY-reactive autoAbs between patients with major
      depression and healthy controls. Then, to evaluate if changes of NPY autoAb
      properties can be causally related to altered mood and appetite, we developed
      central and peripheral passive transfer models of human autoAbs in mice and
      studied depressive-like behavior in forced-swim test and food intake. We found
      that plasma levels of NPY IgG autoAbs were lower in patients with moderate but
      not with mild depression correlating negatively with the Montgomery-Asberg
      Depression Rating Scale scores and with immobility time of the forced-swim test
      in mice after peripheral injection of autoAbs. No significant differences in NPY
      IgG autoAb affinities between patients with depression and controls were found,
      but higher affinity of IgG autoAbs for NPY was associated with lower body mass
      index and prevented NPY-induced orexigenic response in mice after their central
      injection. These data suggest that changes of plasma levels of anti-NPY autoAbs
      are relevant to altered mood, while changes of their affinity may participate in
      altered appetite and body weight in patients with depressive disorder.

PMID- 22365483
TI  - Timing matters: long term effects of adversities from prenatal period up to
      adolescence on adolescents' cortisol stress response. The TRAILS study.
AB  - OBJECTIVE: Altered cortisol response is a vulnerability marker for a variety of
      stress-related diseases and psychiatric disorders. Childhood adversity has been
      shown to modify this response, but evidence is inconsistent. Effects may differ
      depending on the timing of exposure, or due to the interplay between
      pre/postnatal adversity and later adversities. The present study examined the
      influence of adversity during different timeframes (pre/postnatal, ages 0-5, 6
      11, 12-13, 14-15 years), and the interaction between pre/postnatal and later
      adversity on adolescents' cortisol stress response. METHOD: Four salivary
      cortisol samples were collected before and after a social stress test in 471 16
      year-old adolescents from the longitudinal study TRAILS. Data on pre/postnatal
      exposure to adversities were obtained from Preventive Child Healthcare records
      and parental reports, subsequent adversities from parental and self-reports.
      RESULTS: Pre/postnatal adversity was associated with increased cortisol
      reactivity. Adversities during ages 0-5 were not associated with cortisol
      outcomes. Adversities during ages 6-11 were associated with a high cortisol
      level, especially in those exposed to pre/postnatal adversity, while adversities
      during ages 12-13 and 14-15 were associated with a low cortisol level.
      CONCLUSIONS: Results highlight the importance to take the timing of stress
      exposure into account. In addition to programming effects, pre/postnatal
      adversity interacts with childhood adversity in producing deviant cortisol
      levels. Puberty may be marked by a transition in how adversities affect the HPA
      axis, with cortisol hypersecretion before age 11 and hyposecretion after age 11.

PMID- 22365484
TI  - The Active Straight Leg Raise test in lumbopelvic pain during pregnancy.
AB  - Although many properties of the Active Straight Leg Raise (ASLR) test as a
      diagnostic test in lumbopelvic pain (LPP) are well documented, various elements
      are lacking. A cross-sectional study was performed to compute sensitivity and
      specificity, to assess the advantages and disadvantages of various cutoff points,
      to analyze the relation between the ASLR test and the Posterior Pelvic Pain
      Provocation (PPPP) test, and to investigate the relation with confounders. Data
      of 110 women with LPP and 72 without LPP were available. The advantages and
      disadvantages of four cutoff points of ASLR, and combinations of the ASLR and
      PPPP, were investigated by comparing sensitivity, specificity and area under the
      curves (AUC) of receiver operating characteristic curves (ROC). The influence of
      the site of pain was analyzed by means of AUC. The relation with confounders was
      measured using Pearson correlation coefficients. Results show that for diagnostic
      use the best cutoff for the ASLR test in pregnancy is between score 0 and 1.
      Specificity of the ASLR test is good (88%). Sensitivity for all types of LPP
      during pregnancy is moderate (54%), and is larger in case of more pain and
      disability. When combined with the PPPP test, sensitivity of the ASLR test is
      larger (68%). Isolated symphyseal pain, isolated low back pain and isolated
      coccyx pain are not diagnosed by these two tests. The ASLR test is not influenced
      by age, number of previous deliveries, BMI, cause of LPP (pregnancy-related or
      not), the existence of urinary incontinence and/or level of fatigue.

PMID- 22365485
TI  - Neuromuscular transmission modulation by adenosine upon aging.
AB  - In infant rats adenosine A(2A) receptor-mediated modulation of neuromuscular
      transmission predominates over A1 receptor-mediated neuromodulation. We
      investigated whether aging affects this A(2A)/A(1) receptor balance. Evoked
      (EPPs) and miniature end plate potentials (MEPPs) were recorded from single
      fibers of (weeks-old) infant (3-4), young adult (12-16), older (36-38), and aged
      (80-90) male rat-diaphragm. The non A1/A(2A) selective agonist, 2-chloroadenosine
      (CADO; 30 nM) and the adenosine kinase inhibitor, iodotubericidin (ITU; 10 MUM)
      increased mean amplitude and quantal content of EPPs in infant, young adult, and
      older adult rats, but not in aged rats. The facilitatory effects were prevented
      by the A(2A) receptor antagonist, ZM241385 (50 nM) and mimicked by the A(2A)
      receptor agonist, CGS21680 (10 nM). The A1 receptor agonist, 6
      cyclopentyladenosine (CPA; 100 nM), decreased EPPs amplitude in all age groups.
      It is concluded that aging differently influences adenosine A1 receptor and A(2A)
      receptor-mediated presynaptic modulation of neuromuscular transmission, so that
      the facilitatory influence decreases upon aging, whereas the inhibitory influence
      remains unchanged in aged animals. The reduction of adenosine A(2A) receptors
      upon aging may contribute to the age-related changes in neuromuscular function.

PMID- 22365486
TI  - Resting metabolic connectivity in prodromal Alzheimer's disease. A European
      Alzheimer Disease Consortium (EADC) project.
AB  - We explored resting-state metabolic connectivity in prodromal Alzheimer's disease
      (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional
      correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography
      (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose
      positron emission tomography of 36 patients with amnestic mild cognitive
      impairment who converted to Alzheimer's disease (AD) dementia after an average
      time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism
      in pAD showed less metabolic connectivity in patients than in CTR
      (autocorrelation and correlation with large temporal and frontal areas,
      respectively). pAD patients showed limited correlation even in selected
      nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal
      cortex (DLFC). On the contrary, in CTR group correlation was highlighted between
      hippocampi and precuneus/posterior cingulate and frontal cortex, and between
      dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The
      reduced metabolic connections both in hypometabolic and nonhypometabolic areas in
      pAD patients suggest that metabolic disconnection (reflecting early diaschisis)
      may antedate remote hypometabolism (early sign of synaptic degeneration).

PMID- 22365487
TI  - Computed tomographic measurement of gender differences in bowing of the sagittal
      femoral shaft in persons older than 50 years.
AB  - Surgeons do not give enough weight to the effects of bowing of the sagittal
      femoral shaft in total knee arthroplasty (TKA), which can result in damage to the
      cortex, fractures, or malalignment of the femoral component. To determine gender
      differences in bowing, we used spiral computed tomography to scan the femurs of
      26 men and 47 women older than 50 years who required TKA. Skeletal extraction of
      the total sagittal femoral shaft from computed tomographic images was done by a
      matrix laboratory. The extracted curves were evenly divided into 3 sections.
      Comparison of the curvature on different sections of the same side of the femur
      showed that the distal third was significantly bowed. In addition, the curvature
      of the distal third was significantly larger in women than in men. Such
      morphological characteristics put forward new requirements in how intramedullary
      guide rods are used in TKA.

PMID- 22365488
TI  - Detection of total knee prostheses at airport security checkpoints.
AB  - Airport security screening measures have changed substantially during the past
      decade, but few reports have examined how this affects patients who have
      undergone knee arthroplasties. The purpose of this study was to characterize the
      efficacy of airport metal detection of total knee prostheses, the delays faced,
      any inconvenience this may have caused, and the role of implant identification
      cards. Ninety-seven total knee arthroplasty recipients reported passing through
      an airport metal detector, with 70 triggering the alarm a mean of 3 times (range,
      1-36). The presence of a single-knee prosthesis triggered airport security alarms
      more than 83% of the time and increased patient inconvenience. Patients should be
      informed about this chance and be prepared to present documentation of their
      prosthesis.

PMID- 22365489
TI  - Functional and physiological outcomes from an exercise-based dysphagia therapy: a
      pilot investigation of the McNeill Dysphagia Therapy Program.
AB  - OBJECTIVE: To investigate functional and physiological changes in swallowing
      performance of adults with chronic dysphagia after an exercise-based dysphagia
      therapy. DESIGN: Intervention study: before-after trial with 3-month follow-up
      evaluation. SETTING: Outpatient clinic within a tertiary care academic health
      science center. PARTICIPANTS: Adults (N=9) with chronic (>12 mo) dysphagia after
      unsuccessful prior therapies. Subjects were identified from among patients
      referred to an outpatient dysphagia clinic. Subjects had dysphagia secondary to
      prior treatment for head/neck cancer or from neurologic injury. All subjects
      demonstrated clinical and fluoroscopic evidence of oropharyngeal dysphagia. No
      subject withdrew during the course of this study. INTERVENTIONS: All subjects
      completed 3 weeks of an intensive, exercise-based dysphagia therapy. Therapy was
      conducted daily for 1h/d, with additional activities completed by subjects each
      night between therapy sessions. MAIN OUTCOME MEASURES: Primary outcomes were
      clinical and functional change in swallowing performance with maintenance at 3
      months after intervention. Secondary, exploratory outcomes included physiological
      change in swallow performance measured by hyolaryngeal elevation, lingual-palatal
      and pharyngeal manometric pressure, and surface electromyographic amplitude.
      RESULTS: Clinical and functional swallowing performances improved significantly
      and were maintained at the 3-month follow-up examination. Subject perspective
      (visual analog scale) on functional swallowing also improved. Four of 7 subjects
      who were initially feeding tube dependent progressed to total oral intake after 3
      weeks of intervention. Physiological indices demonstrated increased swallowing
      effort after intervention. CONCLUSIONS: Significant clinical and functional
      improvement in swallowing performance followed a time-limited (3 wk) exercise
      based intervention in a sample of subjects with chronic dysphagia. Physiological
      changes after therapy implicate improved neuromuscular functioning within the
      swallow mechanism.

PMID- 22365490
TI  - The impact of retirement on the drinking patterns of older adults: a review.
AB  - OBJECTIVE: Due to the aging of the population, there is renewed focus on the
      public health issues of middle-aged and older adults. One area of such focus is
      unhealthy drinking, and researchers seek to understand the unique developmental
      risk and protective factors among those entering older adulthood. Retirement has
      been hypothesized as a contributing factor in the onset and maintenance of
      unhealthy drinking in late life. This review describes the relevant theories and
      critically reviews empirical evidence that explores the relationship between
      alcohol and retirement drawn from both the industrial and organizational
      psychology and substance misuse literatures. METHOD: Using four research
      databases, thirteen studies published in the last 25years that investigated the
      relationship of retirement and alcohol use and met specific selection criteria
      were reviewed. RESULTS: The literature suggests that retirement may not have a
      strong direct impact on drinking behaviors or problems, but attributes of the
      process (e.g. retirement voluntariness) of transition to retirement and
      individual attributes, such as having a history of problem drinking, may
      facilitate or inhibit drinking. CONCLUSIONS: Future research should delve into
      the social context of drinking in retirement with a goal of understanding the
      aspects and conditions of retirement that increase risk of alcohol problems.
      Investigation should also examine heterogeneity in retirement drinking patterns
      with a goal of identifying subpopulations that are at greater risk.

PMID- 22365491
TI  - Impact of thromboprophylaxis guidelines on clinical outcomes following total hip
      and total knee replacement.
AB  - BACKGROUND: The American College of Chest Physicians (ACCP) guidelines recommends
      thromboprophylaxis for total hip replacement (THR) and total knee replacement
      (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines
      among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE),
      bleeding event rates and risk factors for VTE between patients receiving ACCP
      recommended thromboprophylaxis ('ACCP') and those who did not ('non-ACCP').
      METHODS: This retrospective observational study used a large US health plan
      claims database that was linked to an inpatient database containing detailed
      inpatient medication use and a database containing date-of-death information.
      Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006
      were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP
      patients were analyzed using chi-squared tests and multivariate logistic
      regression. RESULTS: Of 3,497 linked patients, 1,395 (40%) received ACCP
      recommended thromboprophylaxis. Of the patients who received non-ACCP recommended
      prophylaxis the majority (81%) received shorter than the recommended minimum 10
      day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non
      ACCP patients were almost twice as likely to experience an incident DVT (3.76%
      versus 2.01%, p=0.003) and more than eight times as likely to experience an
      incident PE (1.19% versus 0.14%, p=0.001) relative to ACCP patients; there were
      no statistically significant difference in bleeding rates. Multivariate logistic
      regression indicated that the odds of a VTE event were significantly lower for
      ACCP patients (DVT: OR=0.54; p=0.006; PE: OR=0.12; p=0.004). CONCLUSIONS: This
      study offers a unique perspective on 'real-world' thromboprophylaxis patterns and
      associated outcomes in THR and TKR patients in the US. It suggests that only 40%
      of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not
      receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and
      PE.

PMID- 22365492
TI  - Pregnancy-related venous thromboembolism: risk and the effect of
      thromboprophylaxis.
AB  - Venous thromboembolism (VTE) is a leading cause of maternal mortality and
      morbidity during pregnancy in developed countries. The incidence of VTE per
      pregnancy-year increases about 4-fold during pregnancy and at least 14-fold
      during the puerperium. Risk factors include a personal history of VTE, presence
      of inherited or acquired thrombophilia, a family history of VTE and general
      medical conditions, such as immobilisation, overweight, varicose veins, some
      haematological diseases and inflammatory disorders. VTE is considered potentially
      preventable with the prophylactic administration of anticoagulants, but there are
      no high quality randomized clinical trials that compared different strategies of
      thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against
      the risks of exposure to anticoagulants, this review provides advice regarding
      which women may benefit from thromboprophylaxis during and after pregnancy.

PMID- 22365493
TI  - Primary care and diagnosis of cancer.

PMID- 22365494
TI  - Variation in number of general practitioner consultations before hospital
      referral for cancer: findings from the 2010 National Cancer Patient Experience
      Survey in England.
AB  - BACKGROUND: Information from patient surveys can help to identify patient groups
      and cancers with the greatest potential for improvement in the experience and
      timeliness of cancer diagnosis. We aimed to examine variation in the number of
      pre-referral consultations with a general practitioner between patients with
      different cancers and sociodemographic characteristics. METHODS: We analysed data
      from 41,299 patients with 24 different cancers who took part in the 2010 National
      Cancer Patient Experience Survey in England. We examined variation in the number
      of general practitioner consultations with cancer symptoms before hospital
      referral to diagnose cancer. Logistic regression was used to identify independent
      predictors of three or more pre-referral consultations, adjusting for cancer
      type, age, sex, deprivation quintile, and ethnic group. FINDINGS: We identified
      wide variation between cancer types in the proportion of patients who had visited
      their general practitioner three or more times before hospital referral (7.4%
      [625 of 8408] for breast cancer and 10.1% [113 of 1124] for melanoma; 41.3% [193
      of 467] for pancreatic cancer and 50.6% [939 of 1854] for multiple myeloma). In
      multivariable analysis, with patients with rectal cancer as the reference group,
      those with subsequent diagnosis of multiple myeloma (odds ratio [OR] 3.42, 95% CI
      3.01-3.90), pancreatic cancer (2.35, 1.91-2.88), stomach cancer (1.96, 1.65
      2.34), and lung cancer (1.68, 1.48-1.90) were more likely to have had three or
      more pre-referral consultations; conversely patients with subsequent diagnosis of
      breast cancer (0.19; 0.17-0.22), melanoma (0.34, 0.27-0.43), testicular cancer
      (0.47, 0.33-0.67), and endometrial cancer (0.59, 0.49-0.71) were more likely to
      have been referred to hospital after only one or two consultations. The
      probability of three or more pre-referral consultations was greater in young
      patients (OR for patients aged 16-24 years vs 65-74 years 2.12, 95% CI 1.63-2.75;
      p<0.0001), those from ethnic minorities (OR for Asian vs white 1.73, 1.45-2.08;
      p<0.0001; OR for black vs white 1.83, 1.51-2.23; p<0.0001), and women (OR for
      women vs men 1.28, 1.21-1.36; p<0.0001). We identified strong evidence of
      interactions between cancer type and age group and sex (p<0.0001 for both), and
      between age and ethnicity (p=0.0013). The model including these interactions
      showed a particularly strong sex effect for bladder cancer (OR for women vs men
      2.31, 95% CI 1.98-2.69) and no apparent ethnic group differences in young
      patients aged 16-24 years, whilst the only cancers without an apparent age
      gradient were testicular cancer and mesothelioma. INTERPRETATION: Our findings
      could help to prioritise and stratify early diagnosis initiatives and research,
      focusing on patients with cancers and sociodemographic characteristics with the
      largest potential for improvement. FUNDING: None.

PMID- 22365496
TI  - Transcription factories: genetic programming in three dimensions.
AB  - Among the most intensively studied systems in molecular biology is the eukaryotic
      transcriptional apparatus, which expresses genes in a regulated manner across
      hundreds of different cell types. Several studies over the past few years have
      added weight to the concept that transcription takes place within discrete
      'transcription factories' assembled inside the cell nucleus. These studies apply
      innovative technical approaches to gain insights into the molecular constituents,
      dynamical behaviour and organizational regulators of transcription factories,
      providing exciting insights into the spatial dimension of transcriptional
      control.

PMID- 22365495
TI  - Replication stress and mechanisms of CNV formation.
AB  - Copy number variants (CNVs) are widely distributed throughout the human genome,
      where they contribute to genetic variation and phenotypic diversity. De novo CNVs
      are also a major cause of numerous genetic and developmental disorders. However,
      unlike many other types of mutations, little is known about the genetic and
      environmental risk factors for new and deleterious CNVs. DNA replication errors
      have been implicated in the generation of a major class of CNVs, the nonrecurrent
      CNVs. We have found that agents that perturb normal replication and create
      conditions of replication stress, including hydroxyurea and aphidicolin, are
      potent inducers of nonrecurrent CNVs in cultured human cells. These findings have
      broad implications for identifying CNV risk factors and for hydroxyurea-related
      therapies in humans.

PMID- 22365497
TI  - Double-strand break repair and recombination-dependent replication of DNA in
      bacteriophage T4 in the absence of UvsX recombinase: replicative resolution
      pathway.
AB  - The effects of mutations in bacteriophage T4 genes uvsX and 49 on the double
      strand break (DSB)-promoted recombination were studied in crosses, in which DSBs
      were induced site-specifically within the rIIB gene by SegC endonuclease in the
      DNA of only one of the parents. Frequency of rII+ recombinants was measured in
      two-factor crosses of the type i*ets1 and in three-factor crosses of the type
      i*ets1 a6, where ets1 is an insertion in the rIIB gene carrying the cleavage site
      for SegC; i's are rIIB or rIIA point mutations located at various distances (12
      2040 bp) from the ets1 site, and a6 is rIIA point mutation located at 2040 bp
      from ets1. The frequency/distance relationships were obtained in crosses of the
      wild-type phage and of the amber mutant S17 (gene uvsX) and the double mutant S17
      E727 (genes uvsX and 49). These data provide information about the frequency and
      distance distribution of the single-exchange (splices) and double-exchange
      (patches) events. The extended variant of the splice/patch coupling (SPC) model
      of recombination, which includes transition to the replication resolution (RR)
      alternative is substantiated and used for interpretation of the
      frequency/distance relationships. We conclude that the uvsX mutant executes
      recombination-dependent replication but does it by a qualitatively different way.
      In the absence of UvsX function, the DSB repair runs largely through the RR
      subpathway because of inability of the mutant to form a Holliday junction. In the
      two-factor crosses, the double uvsX 49- is recombinationally more proficient than
      the single uvsX mutant (partial suppression of the uvsX deficiency), while the
      patch-related double exchanges are virtually eliminated in this background.

PMID- 22365498
TI  - Release from quiescence stimulates the expression of human NEIL3 under the
      control of the Ras dependent ERK-MAP kinase pathway.
AB  - Base excision repair (BER) is believed to be the predominant pathway for the
      repair of oxidative DNA damage. BER is initiated by lesion-specific DNA
      glycosylases that recognize and remove the damaged base. NEIL1, NEIL2 and NEIL3
      are three mammalian members of the Fpg/Nei DNA glycosylase family with similar
      enzymatic properties. In this study we showed that both the transcription and
      protein levels of hNEIL3 fluctuated during the cell cycle. Based on predicted
      promoter elements of cell cycle-regulated genes and microarray data from various
      reports, we suggest that hNEIL3 repression in quiescent cells might be mediated
      by the DREAM (DP1, RB p130, E2F4 and MuvB core complex) complex. Release from G0
      by mitogenic stimulation showed an induction of hNEIL3 in early S phase under the
      control of the Ras dependent ERK-MAP kinase pathway. In contrast, the total
      expression of hNEIL1 was downregulated upon release from quiescence while the
      expression of hNEIL2 was cell cycle independent. Notably, hNEIL3 showed a similar
      regulation pattern as the replication protein hFEN1 supporting a function of
      hNEIL3 in replication associated repair. Thus, it appears that specialized
      functions of the NEILs are ensured by their expression patterns.

PMID- 22365500
TI  - Large deforming buoyant embolus passing through a stenotic common carotid artery:
      a computational simulation.
AB  - Arterial embolism is responsible for the death of lots of people who suffers from
      heart diseases. The major risk of embolism in upper limbs is that the ruptured
      particles are brought into the brain, thus stimulating neurological symptoms or
      causing the stroke. We presented a computational model using fluid-structure
      interactions (FSI) to investigate the physical motion of a blood clot inside the
      human common carotid artery. We simulated transportation of a buoyant embolus in
      an unsteady flow within a finite length tube having stenosis. Effects of stenosis
      severity and embolus size on arterial hemodynamics were investigated. To fulfill
      realistic nonlinear property of a blood clot, a rubber/foam model was used. The
      arbitrary Lagrangian-Eulerian formulation (ALE) and adaptive mesh method were
      used inside fluid domain to capture the large structural interfacial movements.
      The problem was solved by simultaneous solution of the fluid and the structure
      equations. Stress distribution and deformation of the clot were analyzed and
      hence, the regions of the embolus prone to lysis were localized. The maximum
      magnitude of arterial wall shear stress during embolism occurred at a short
      distance proximal to the throat of the stenosis. Through embolism, arterial
      maximum wall shear stress is more sensitive to stenosis severity than the embolus
      size whereas role of embolus size is more significant than the effect of stenosis
      severity on spatial and temporal gradients of wall shear stress downstream of the
      stenosis and on probability of clot lysis due to clot stresses while passing
      through the stenosis.

PMID- 22365499
TI  - Which diameter and angle rule provides optimal flow patterns in a coronary
      bifurcation?
AB  - The branching angle and diameter ratio in epicardial coronary artery bifurcations
      are two important determinants of atherogenesis. Murray's cubed diameter law and
      bifurcation angle have been assumed to yield optimal flows through a bifurcation.
      In contrast, we have recently shown a 7/3 diameter law (HK diameter model), based
      on minimum energy hypothesis in an entire tree structure. Here, we derive a
      bifurcation angle rule corresponding to the HK diameter model and critically
      evaluate the streamline flow through HK and Murray-type bifurcations. The
      bifurcations from coronary casts were found to obey the HK diameter model and
      angle rule much more than Murray's model. A finite element model was used to
      investigate flow patterns for coronary artery bifurcations of various types. The
      inlet velocity and pressure boundary conditions were measured by ComboWire. Y
      bifurcation of Murray type decreased wall shear stress-WSS (10%-40%) and created
      an increased oscillatory shear index-OSI in atherosclerosis-prone regions as
      compared with HK-type bifurcations. The HK-type bifurcations were found to have
      more optimal flow patterns (i.e., higher WSS and lower OSI) than Murray-type
      bifurcations which have been traditionally believed to be optimized. This study
      has implications for changes in bifurcation angles and diameters in percutaneous
      coronary intervention.

PMID- 22365501
TI  - Quantitative analysis of exogenous IGF-1 administration of intervertebral disc
      through intradiscal injection.
AB  - Exogenous administration of IGF-1 has been proposed as a therapy for disc
      degeneration. The objectives of this study were to develop a numerical model for
      quantitatively analysing exogenous administration of IGF-1 into the
      intervertebral disc (IVD) via intradiscal injection and to investigate the
      effects of IGF-1 administration on distribution of glucose and oxygen in the IVD.
      In this study, the reversible binding reaction between IGF-1 and IGF binding
      proteins was incorporated into the mechano-electrochemical mixture model. The
      model was used to numerically analyse transport of IGF-1, glucose, oxygen and
      lactate in the IVD after IGF-1 administration. The enhancement of IGF-1 on
      lactate production was also taken into account in the theoretical model. The
      numerical analyses using finite element method demonstrated that the binding
      reactions significantly affect the time-dependent distribution of IGF-1 in the
      IVD. It was found that the region affected by IGF-1 was smaller and the duration
      of the therapeutic IGF-1 level was longer in the degenerated disc with a higher
      concentration of IGF binding proteins. It was also found that the IGF-1 injection
      can reduce glucose concentration and increase lactate accumulation (i.e., lower
      pH) in the IVD and these influences were regulated by the IGF-1 binding
      reactions. This study indicated the complexity of intradiscal administration of
      growth factors, which needs to be fully analysed in order to achieve a successful
      outcome. The new theoretical model developed in this study can serve as a
      powerful tool in analysing and designing the optimal treatments of growth factors
      for disc degeneration.

PMID- 22365502
TI  - [Anuric acute renal failure after suprapubic catheterization].
AB  - Percutaneous suprapubic catheterization is an alternative when placement of a
      urethral catheter is contraindicated or unsuccessful. We report the case of a 3
      day-old newborn, who presented anuric acute renal failure secondary to placement
      of a suprapubic catheter. An excessive length of catheter had been inserted into
      the bladder and was obstructing the vesicoureteral junctions. Several measures
      can be taken to prevent this complication, such as systematic measurement of the
      length inserted into the bladder, use of a catheter with 1cm gradations or
      recourse to radiopaque material.

PMID- 22365503
TI  - Alpha-1-antitrypsin and other proteinase inhibitors.
AB  - Since the end of the 1980s augmentation therapy with alpha-1 antitrypsin (AAT)
      from human plasma has been available for specific treatment of emphysema due to
      AAT deficiency. Intravenous augmentation therapy has demonstrated to be safe and
      weekly infusions of AAT have demonstrated to result in plasma AAT concentration
      above those considered protective for the lungs. Randomized, placebo-controlled
      clinical trials have confirmed a reduction in the decline in lung density in
      patients receiving augmentation therapy. This is the first example of an
      antiprotease effective in restoring the protease/antiprotease imbalance in the
      lungs and changing the natural history of congenital emphysema. On the basis of
      the results obtained with the long-term infusion of AAT, there is growing
      interest in the possible use of antiprotease treatment in patients with smokers
      COPD. However, no drugs are yet available to increase antiprotease protection of
      the lower airways of smokers.

PMID- 22365504
TI  - Signaling and aging at the neuromuscular synapse: lessons learnt from
      neuromuscular diseases.
AB  - The neuromuscular junction (NMJ) is a specialized synapse between motor neurons
      and skeletal muscle with a complex signaling network that assures highly reliable
      neuromuscular transmission. Diseases of the NMJ cause skeletal muscle fatigue and
      include inherited and acquired disorders that affect presynaptic, intrasynaptic
      or postsynaptic components. Moreover, fragmentation of the NMJ contributes to
      sarcopenia, the loss of muscle mass during aging. Studies from recent years
      indicate that the formation and stabilization of NMJs differs between various
      muscles and that this difference affects their response under pathological
      conditions. This review summarizes the most important mechanisms involved in the
      development, maintenance and dysfunction of the NMJ and it discusses their
      significance in myasthenic disorders and aging and as targets for possible future
      treatment of NMJ dysfunction.

PMID- 22365505
TI  - Invited commentary.

PMID- 22365506
TI  - Is chlorhexidine-alcohol more effective than povidone-iodine?

PMID- 22365507
TI  - Nipple micro-anatomy: ductal epithelial types.

PMID- 22365508
TI  - Is it time to lower the recommended screening age for colorectal cancer?

PMID- 22365510
TI  - Evaluating the validity of CT in complicated gallstone disease.

PMID- 22365514
TI  - Prognostic factors and staging for soft tissue sarcomas: an update.
AB  - Soft tissue sarcoma (STS) staging is a constantly evolving process. Grading is
      still of utmost importance and has been adapted into a three-tier system. The STS
      most difficult to categorize are those with uncertain malignant potential, such
      as solitary fibrous tumors, gastrointestinal stromal tumors, and glomus tumors,
      some of which have developed completely separate staging systems and may not even
      be considered sarcomas. Beyond the current TNM staging system, a multitude of
      prognostic factors for STS will continue to be discovered and ultimately
      incorporated into future revisions of the staging system.

PMID- 22365515
TI  - Modern surgical therapy: limb salvage and the role of amputation for extremity
      soft-tissue sarcomas.
AB  - Historically the surgical management of extremity soft-tissue sarcomas (ESTS)
      commonly involved amputation. Nowadays limb-sparing, function-preserving surgery
      is the standard of care for ESTS. Adjuvant therapies such as radiation therapy
      and chemotherapy are used selectively in an effort to minimize both local
      recurrence and distant spread. Less common modalities, such as isolated limb
      perfusion, isolated limb infusion, and hyperthermia are being evaluated to
      potentially expand the cohort of individuals who may be eligible for limb-sparing
      surgery and to improve outcomes. This article reviews the standard and evolving
      approaches to the management of ESTS.

PMID- 22365516
TI  - Radiation therapy: neoadjuvant, adjuvant, or not at all.
AB  - Clinical trial data show that radiation enhances local tumor control of extremity
      sarcomas with acceptable morbidity when sophisticated radiation techniques are
      combined with limb-sparing resections performed by oncologic surgeons with
      sarcoma expertise. Similar controlled data is not available for retroperitoneal
      sarcomas but some studies suggest a benefit for radiotherapy. Radiation can be
      delivered by external beam or brachytherapy; it can be given pre-operatively,
      post-operatively, or intra-operatively. Indications for and advances in radiation
      therapy are discussed in this article.

PMID- 22365517
TI  - Adjuvant chemotherapy for soft tissue sarcomas.
AB  - Soft tissue sarcomas are rare mesenchymal neoplasms with considerable
      heterogeneity in biologic behavior and response to systemic therapy. Most
      patients present with localized disease and are potentially curable with
      multidisciplinary treatment. In patients with a high risk of developing
      metastatic disease, optimal use of neoadjuvant/adjuvant therapy has a definite
      role in improving patient outcomes by decreasing local and distant recurrences.
      Histology-specific clinical trials enrolling a homogenous high-risk population
      have been more successful in demonstrating benefit than larger trials with
      unselected heterogeneous patient populations. In specific histologic subtypes
      responsive to chemotherapy, neoadjuvant chemotherapy with close monitoring of
      response is recommended.

PMID- 22365518
TI  - Margin status, local recurrence, and survival: correlation or causation?
AB  - The relationship between surgical margin status and outcomes in sarcoma has been
      an area of controversy for years. Some question whether a positive margin
      represents inadequate surgery or perhaps is a marker of aggressive cancer
      biology. This article reviews the literature regarding the natural history of
      positive margins and its possible influence on sarcoma recurrence and survival.

PMID- 22365519
TI  - Pulmonary metastasectomy for soft tissue sarcoma.
AB  - The American Cancer Society predicts 10,520 new cases and 3920 deaths from soft
      tissue sarcoma (STS) for 2010. STS disseminates primarily via the hematogenous
      route, although lymphatic spread does occur with certain subtypes. The lung is
      the most common metastatic site in most large series, accounting for up to 80% of
      metastases. The median overall survival for pulmonary metastatic disease with
      current multidisciplinary treatment is approximately 12 to 14 months. Pulmonary
      metastasectomy (PM) represents the only potentially curative treatment for
      patients with STS and lung metastases. This article discusses the management of
      STS using PM.

PMID- 22365520
TI  - Isolated regional therapy for advanced extremity soft tissue sarcomas.
AB  - Patients presenting with unresectable, large, primary or recurrent extremity soft
      tissue sarcoma or locally advanced extremity tumors may benefit from treatment
      options in the form of isolated regional perfusion therapy. Hyperthermic isolated
      limb perfusion (HILP) and isolated limb infusion (ILI) have proved to be
      efficacious with acceptable systemic and regional toxicity profiles. Both
      procedures are attractive as options for patients who might otherwise be facing
      amputation as limb salvage procedures. HILP and ILI can be offered as either
      definitive treatment or as neoadjuvant therapy followed by surgery and/or
      radiation treatment. Response rates are encouraging as are limb preservation
      rates after regional therapy. Ongoing multicenter collaborations and clinical
      trials are required to gain knowledge on HILP and ILI for unresectable extremity
      sarcoma and expand the indications for use in the management of advanced
      extremity soft tissue sarcoma.

PMID- 22365522
TI  - Improving outcomes for retroperitoneal sarcomas: a work in progress.
AB  - This article presents the current understanding of prognostic factors and
      outcomes for retroperitoneal sarcoma. The discussion focuses on the literature
      published since 2000, including studies with cohorts of at least 30 patients. An
      interpretation of factors that have contributed to an improvement in outcomes has
      been performed. With demonstration of the potential for good long-term outcomes
      and a better appreciation for the importance of minimizing treatment-related
      morbidity, the international sarcoma community has increasingly recognized and
      emphasized the importance of expert multidisciplinary assessment and care for
      this rare malignancy.

PMID- 22365521
TI  - Updates on the management of gastrointestinal stromal tumors.
AB  - Despite being the most common sarcoma of the gastrointestinal tract,
      gastrointestinal stromal tumor (GIST) has been widely recognized as a unique
      entity for just over a decade. The advent of tyrosine kinase inhibitors has
      revolutionized the diagnosis and treatment of GIST. Although surgery remains the
      only chance for cure, multimodal treatment that includes molecular therapy
      continues to develop. Optimal management of GIST requires careful radiographic,
      pathologic, medical, and surgical care, emphasizing the need for a
      multidisciplinary approach. This review highlights recent developments in the
      management of GIST.

PMID- 22365523
TI  - Atypical lipomatous tumor/well-differentiated liposarcoma: what is it?
AB  - Liposarcoma (LPS) is the most common soft tissue sarcoma, frequently found in the
      thigh and retroperitoneum. LPS is commonly classified into well-differentiated
      LPS and dedifferentiated LPS. Histologic subtype, tumor location, and
      completeness of surgical resection are important prognostic indicators for LPS.
      Magnetic resonance imaging best characterizes extremity lesions, whereas computed
      tomography is most often used for intra-abdominal and retroperitoneal tumors.
      Surgical resection is the mainstay of treatment. Adjuvant radiation is considered
      for close margins. Survival for extremity tumors is favorable. However,
      difficulty in obtaining wide margins in the retroperitoneum predisposes to local
      recurrence and, ultimately, death from unresectable disease.

PMID- 22365524
TI  - Sarcomas and the immune system: implications for therapeutic strategies.
AB  - Soft-tissue sarcomas are a heterogeneous group of tumors that are capable of
      generating host immune responses. Historically the role of antitumor immunity was
      first studied in soft-tissue sarcomas. Subsequent in vitro studies, preclinical
      models, and clinical observations have provided ample evidence for an immunologic
      approach to sarcoma treatment. Initial clinical trials involving vaccines and
      adoptive immunotherapy have demonstrated promising results. The continued search
      for sarcoma tumor-associated antigens as specific targets is central to the
      clinical translation of effective immunotherapies.

PMID- 22365525
TI  - Surgical Oncology Clinics of North America. Foreword.

PMID- 22365526
TI  - Soft tissue sarcoma. Preface.

PMID- 22365527
TI  - Use of the i-gel for tracheal intubation without the interruption of chest
      compressions.

PMID- 22365528
TI  - T-cell lymphoblastic leukemia as a rare cause of bilateral nephromegaly.

PMID- 22365529
TI  - Post-traumatic stress disorder in an emergency department population one year
      after Hurricane Katrina.
AB  - BACKGROUND: Hurricane Katrina resulted in a significant amount of injury, death,
      and destruction. STUDY OBJECTIVES: To determine the prevalence of, and risk
      factors for, symptoms of post-traumatic stress disorder (PTSD) in an emergency
      department (ED) population, 1 year after hurricane Katrina. METHODS: Survey data
      including the Primary Care PTSD (PC-PTSD) screening instrument, demographic data,
      and questions regarding health care needs and personal loss were collected and
      analyzed. RESULTS: Seven hundred forty-seven subjects completed the survey. The
      PC-PTSD screen was positive in 38%. In the single variate analysis, there was a
      correlation with a positive PC-PTSD screen and the following: staying in New
      Orleans during the storm (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.28
      2.34), having material losses (OR 1.64, 95% CI 1.03-2.60), experiencing the death
      of a loved one (OR 1.96, 95% CI 1.35-1.87), needing health care during the storm
      (OR 2.01, 95% CI 1.48-2.73), and not having health care needs met during the
      storm (OR 2.00, 95% CI 1.26-3.18) or after returning to New Orleans (OR 2.29, 95%
      CI 1.40-3.73). In the multivariate analysis, the death of a loved one (OR 1.87,
      95% CI 1.26-2.78), being in New Orleans during the storm (OR 1.69, 95% CI 1.22
      2.33), and seeking health care during the storm (OR 1.69, 95% CI 1.22-2.35) were
      associated with positive PC-PTSD screens. CONCLUSIONS: There was a high
      prevalence of PTSD in this ED population surveyed 1 year after hurricane Katrina.
      By targeting high-risk patients, disaster relief teams may be able to reduce the
      impact of PTSD in similar populations.

PMID- 22365530
TI  - Aspiration pneumonia and severe self-poisoning: about the necessity of early
      airway management.

PMID- 22365531
TI  - Sacral decubitus ulcers and bacterial meningitis.

PMID- 22365532
TI  - A review on second- and third-order multivariate calibration applied to
      chromatographic data.
AB  - Quantitative analytical works developed by processing second- and third-order
      chromatographic data are reviewed. The various modes in which data of complex
      structure can be measured are discussed, with chromatographic separation
      providing either one or two of the data dimensions. This produces second-order
      data (matrices from uni-dimensional chromatography with multivariate detection or
      from two-dimensional chromatography) or third-order data (three-dimensional data
      arrays from two-dimensional chromatography with multivariate detection). The
      available algorithms for processing these data are classified and discussed,
      regarding their ability to cope with the ubiquitous phenomenon of retention time
      shifts from run to run. A summary of relevant works applying this combination of
      techniques is presented, with focus on quantitative analytical results. Special
      attention is paid to works achieving the full potentiality of the
      multidimensional data, i.e., the second-order advantage.

PMID- 22365533
TI  - Development and validation of a sensitive LC-MS/MS method for the simultaneous
      quantitation of theophylline and its metabolites in rat plasma.
AB  - A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed
      and validated in rat plasma for the simultaneous quantitation of theophylline and
      its four metabolites: 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX), 1
      methylxanthine (1-MX), and 1-methyluric acid (1-MU). Chromatographic separation
      of these analytes was achieved on a Gemini C18 column (50 mm * 4.60 mm, 5 MUm)
      using reversed phase chromatography. The analytes were monitored by electrospray
      ionization in negative ion multiple reaction monitoring mode. Modification of
      collision energies was performed in parallel with chromatographic separation to
      further eliminate interference peaks. The method was validated from 0.05 to 30
      MUg/mL for 1-MX, 1,3-DMU, 1-MU, and theophylline and from 0.1 to 30 MUg/mL for 3
      MX using 0.2 mL of plasma sample. The intra- and inter-day precision and accuracy
      of the quality control samples at low, medium, and high concentration levels
      exhibited relative standard deviations (RSD) of less than 13% and with relative
      error (RE) values of -8.8% to 9.7%. The method was successfully applied for the
      quantitation of theophylline and its metabolite in rat plasma samples.

PMID- 22365534
TI  - Determination of biomarkers of tobacco smoke exposure in oral fluid using solid
      phase extraction and gas chromatography-tandem mass spectrometry.
AB  - A new, simple and sensitive method was described for the simultaneous
      determination of nicotine, cotinine and trans-3'-hydroxycotinine in oral fluid
      samples using solid-phase extraction and gas chromatography/tandem mass
      spectrometry (GC-MS/MS). This technique was developed using only 0.2 mL of
      sample, and deuterated analogues were used as internal standards. The method was
      found to be linear between 0.5 and 1000 ng/mL, with determination coefficients
      higher than 0.996 for all analytes. Intra- and interday precision and accuracy
      were in conformity with the criteria normally accepted in bioanalytical method
      validation. All analytes were stable in the samples for at least 24h at room
      temperature, for at least 72 h at 25 degrees C in processed samples and for at
      least three freeze/thaw cycles. Absolute recoveries ranged from 89 to 92% for all
      analytes. GC-MS/MS has demonstrated to be a powerful tool for the simultaneous
      quantitation of the analytes, providing adequate selectivity and sensitivity. In
      addition, its performance characteristics allow its routine use in the analysis
      of biomarkers of tobacco smoke exposure, extending the window of analyte
      detection in nicotine cessation programs, using a sample amount as low as 0.2 mL
      of human oral fluid.

PMID- 22365535
TI  - Determination of antimalarial compound, ARB-89 (7beta-hydroxy-artemisinin
      carbamate) in rat serum by UPLC/MS/MS and its application in pharmacokinetics.
AB  - Among all the antimalarial agents, artemisinin and its semi synthetic family of
      analogs are the most potent antimalarials available for the treatment of
      Plasmodium falciparum infections. But these analogs have a few issues such as
      shorter half-lives and low oral bioavailability values. In order to overcome
      these inherent problems, novel artemisinin analogs were synthesized from 7beta
      hydroxy artemisinin by the Department of Medicinal Chemistry, University of
      Mississippi using a new synthesis mechanism. Out of all the 7beta-hydroxy
      artemisinin analogs synthesized, 7beta-hydroxy artemisinin carbamate (ARB-89) was
      chosen as a lead compound because of its high in vitro and in vivo activity. In
      this manuscript, a sensitive and rapid ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the
      quantification of ARB-89 in rat serum. The analysis was carried out on an
      AcquityTM UPLC BEH C(18) column (1.7 MUm, 2.1 mm * 50 mm) with a flow rate of 0.3
      mL/min. The detection was performed on a triple quadrupole tandem mass
      spectrometer in positive electrospray ionization (ESI) mode. The selected mass-to
      charge (m/z) ratio transitions used in the multiple reaction monitoring (MRM) for
      ARB-89 and artemisinin (internal standard) were m/z 778.4>253.4 and m/z
      283.4>151.1 respectively. The calibration curve was linear from 1.00 ng/mL to
      10.0 MUg/mL (r(2)=0.999). A simple protein precipitation method was used for
      extraction. Moreover, the inter-day and intra-day precision values were found to
      be less than 15%. The recoveries of the method ranged from 94.0% to 96.7% at
      three concentrations. ARB-89 in rat serum was found to be stable at room
      temperature for 12h. This method was successfully used to quantitate the novel
      antimalarial compound ARB-89 after intravenous and oral administration to rats.

PMID- 22365536
TI  - In vivo spreading of tau pathology.
AB  - Recent findings have suggested that tau pathology may spread in the brain by a
      prion-like mechanism. In this issue of Neuron, de Calignon et al. (2012)
      recreated an early stage of neurofibrillary tangle pathology to show that tau
      aggregates initially generated in a circumscribed area spread throughout the
      brain and lead to neurodegeneration.

PMID- 22365537
TI  - Bers-ERK Schwann cells coordinate nerve regeneration.
AB  - In this issue of Neuron, Napoli et al. (2012) demonstrate that elevated ERK/MAPK
      signaling in Schwann cells is a crucial trigger for Schwann cell
      dedifferentiation in vivo. Moreover, the authors show that dedifferentiated
      Schwann cells have the potential to coordinate much of the peripheral nerve
      response to injury.

PMID- 22365538
TI  - Suppressive competition: how sounds may cheat sight.
AB  - In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex
      activation directly engages local GABAergic circuits in V1 to induce sound-driven
      hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds
      can directly suppress V1 activity and visual driven behavior.

PMID- 22365539
TI  - Axonal mRNA translation: an unexpected link to axon survival and the
      mitochondrion.
AB  - Localized mRNA translation plays roles in dendrites and axons, but the regulatory
      mechanisms and downstream pathways are not well understood. An article in Cell by
      Yoon et al. (2012) shows that lamin B2, well known as a nuclear protein,
      undergoes regulated synthesis in axons, promoting mitochondrial function and axon
      survival.

PMID- 22365540
TI  - What does it mean to be musical?
AB  - Music can be seen as a model system for understanding gene * environment
      interactions and how these can influence neurocognitive development. The concept
      of musicality, however, is underspecified and not well understood. Here, I
      propose a framework for defining musicality to provide a foundation for studying
      the contributions of biological and environmental factors.

PMID- 22365541
TI  - Deconstructing the neuropathic pain phenotype to reveal neural mechanisms.
AB  - After nerve injury maladaptive changes can occur in injured sensory neurons and
      along the entire nociceptive pathway within the CNS, which may lead to
      spontaneous pain or pain hypersensitivity. The resulting neuropathic pain
      syndromes present as a complex combination of negative and positive symptoms,
      which vary enormously from individual to individual. This variation depends on a
      diversity of underlying pathophysiological changes resulting from the convergence
      of etiological, genotypic, and environmental factors. The pain phenotype can
      serve therefore, as a window on underlying pathophysiological neural mechanisms
      and as a guide for developing personalized pain medicine.

PMID- 22365543
TI  - Hierarchical deployment of factors regulating temporal fate in a diverse neuronal
      lineage of the Drosophila central brain.
AB  - The anterodorsal projection neuron lineage of Drosophila melanogaster produces 40
      neuronal types in a stereotypic order. Here we take advantage of this complete
      lineage sequence to examine the role of known temporal fating factors, including
      Chinmo and the Hb/Kr/Pdm/Cas transcriptional cascade, within this diverse central
      brain lineage. Kr mutation affects the temporal fate of the neuroblast (NB)
      itself, causing a single fate to be skipped, whereas Chinmo null only elicits
      fate transformation of NB progeny without altering cell counts. Notably, Chinmo
      operates in two separate windows to prevent fate transformation (into the
      subsequent Chinmo-indenpendent fate) within each window. By contrast, Hb/Pdm/Cas
      play no detectable role, indicating that Kr either acts outside of the cascade
      identified in the ventral nerve cord or that redundancy exists at the level of
      fating factors. Therefore, hierarchical fating mechanisms operate within the
      lineage to generate neuronal diversity in an unprecedented fashion.

PMID- 22365542
TI  - Rethinking the emotional brain.
AB  - I propose a reconceptualization of key phenomena important in the study of
      emotion-those phenomena that reflect functions and circuits related to survival,
      and that are shared by humans and other animals. The approach shifts the focus
      from questions about whether emotions that humans consciously feel are also
      present in other animals, and toward questions about the extent to which circuits
      and corresponding functions that are present in other animals (survival circuits
      and functions) are also present in humans. Survival circuit functions are not
      causally related to emotional feelings but obviously contribute to these, at
      least indirectly. The survival circuit concept integrates ideas about emotion,
      motivation, reinforcement, and arousal in the effort to understand how organisms
      survive and thrive by detecting and responding to challenges and opportunities in
      daily life.

PMID- 22365544
TI  - Propagation of tau pathology in a model of early Alzheimer's disease.
AB  - Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II)
      toward limbic and association cortices as Alzheimer's disease evolves. However,
      the mechanism involved in this hierarchical pattern of disease progression is
      unknown. We describe a transgenic mouse model in which overexpression of human
      tau P301L is restricted to EC-II. Tau pathology progresses from EC transgene
      expressing neurons to neurons without detectable transgene expression, first to
      EC neighboring cells, followed by propagation to neurons downstream in the
      synaptic circuit such as the dentate gyrus, CA fields of the hippocampus, and
      cingulate cortex. Human tau protein spreads to these regions and coaggregates
      with endogenous mouse tau. With age, synaptic degeneration occurs in the
      entorhinal target zone and EC neurons are lost. These data suggest that a
      sequence of progressive misfolding of tau proteins, circuit-based transfer to new
      cell populations, and deafferentation induced degeneration are part of a process
      of tau-induced neurodegeneration.

PMID- 22365545
TI  - A cascade of morphogenic signaling initiated by the meninges controls corpus
      callosum formation.
AB  - The corpus callosum is the most prominent commissural connection between the
      cortical hemispheres, and numerous neurodevelopmental disorders are associated
      with callosal agenesis. By using mice either with meningeal overgrowth or
      selective loss of meninges, we have identified a cascade of morphogenic signals
      initiated by the meninges that regulates corpus callosum development. The
      meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is
      overcome by the induction of expression of Wnt3 by the callosal pathfinding
      neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the
      cingulate callosal pathfinding axons is developmentally regulated by another BMP
      family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and
      turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn
      under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus,
      the meninges and medial neocortex use a cascade of signals to regulate corpus
      callosum development.

PMID- 22365547
TI  - A central role for the ERK-signaling pathway in controlling Schwann cell
      plasticity and peripheral nerve regeneration in vivo.
AB  - Following damage to peripheral nerves, a remarkable process of clearance and
      regeneration takes place. Axons downstream of the injury degenerate, while the
      nerve is remodeled to direct axonal regrowth. Schwann cells are important for
      this regenerative process. "Sensing" damaged axons, they dedifferentiate to a
      progenitor-like state, in which they aid nerve regeneration. Here, we demonstrate
      that activation of an inducible Raf-kinase transgene in myelinated Schwann cells
      is sufficient to control this plasticity by inducing severe demyelination in the
      absence of axonal damage, with the period of demyelination/ataxia determined by
      the duration of Raf activation. Remarkably, activation of Raf-kinase also induces
      much of the inflammatory response important for nerve repair, including breakdown
      of the blood-nerve barrier and the influx of inflammatory cells. This reversible
      in vivo model identifies a central role for ERK signaling in Schwann cells in
      orchestrating nerve repair and is a powerful system for studying peripheral
      neuropathies and cancer.

PMID- 22365548
TI  - Motor protein KIF1A is essential for hippocampal synaptogenesis and learning
      enhancement in an enriched environment.
AB  - Environmental enrichment causes a variety of effects on brain structure and
      function. Brain-derived neurotrophic factor (BDNF) plays an important role in
      enrichment-induced neuronal changes; however, the precise mechanism underlying
      these effects remains uncertain. In this study, a specific upregulation of
      kinesin superfamily motor protein 1A (KIF1A) was observed in the hippocampi of
      mice kept in an enriched environment and, in hippocampal neurons in vitro, BDNF
      increased the levels of KIF1A and of KIF1A-mediated cargo transport. Analysis of
      Bdnf(+/-) and Kif1a(+/-) mice revealed that a lack of KIF1A upregulation resulted
      in a loss of enrichment-induced hippocampal synaptogenesis and learning
      enhancement. Meanwhile, KIF1A overexpression promoted synaptogenesis via the
      formation of presynaptic boutons. These findings demonstrate that KIF1A is
      indispensable for BDNF-mediated hippocampal synaptogenesis and learning
      enhancement induced by enrichment. This is a new molecular motor-mediated
      presynaptic mechanism underlying experience-dependent neuroplasticity.

PMID- 22365546
TI  - Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is
      required for myelination in the central nervous system.
AB  - Myelination by oligodendrocytes in the central nervous system (CNS) is essential
      for proper brain function, yet the molecular determinants that control this
      process remain poorly understood. The basic helix-loop-helix transcription
      factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein
      (BMP) and Wnt/beta-catenin signaling inhibit myelination. Here we show that these
      opposing regulators of myelination are functionally linked by the Olig1/2 common
      target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an
      essential modulator of CNS myelination. Sip1 represses differentiation inhibitory
      signals by antagonizing BMP receptor-activated Smad activity while activating
      crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated
      target, Smad7, is required for oligodendrocyte differentiation and partially
      rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination
      by blocking the BMP- and beta-catenin-negative regulatory pathways. Thus, our
      findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical
      for promoting CNS myelination and point to new mediators for myelin repair.

PMID- 22365549
TI  - Encoding of luminance and contrast by linear and nonlinear synapses in the
      retina.
AB  - Understanding how neural circuits transmit information is technically challenging
      because the neural code is contained in the activity of large numbers of neurons
      and synapses. Here, we use genetically encoded reporters to image synaptic
      transmission across a population of sensory neurons-bipolar cells in the retina
      of live zebrafish. We demonstrate that the luminance sensitivities of these
      synapses varies over 10(4) with a log-normal distribution. About half the
      synapses made by ON and OFF cells alter their polarity of transmission as a
      function of luminance to generate a triphasic tuning curve with distinct maxima
      and minima. These nonlinear synapses signal temporal contrast with greater
      sensitivity than linear ones. Triphasic tuning curves increase the dynamic range
      over which bipolar cells signal light and improve the efficiency with which
      luminance information is transmitted. The most efficient synapses signaled
      luminance using just 1 synaptic vesicle per second per distinguishable gray
      level.

PMID- 22365551
TI  - Functional split between parietal and entorhinal cortices in the rat.
AB  - Posterior parietal cortex (PPC) and medial entorhinal cortex (MEC) are important
      elements of the neural circuit for space, but whether representations in these
      areas are controlled by the same factors is unknown. We recorded single units
      simultaneously in PPC and MEC of freely foraging rats and found that a subset of
      PPC cells are tuned to specific modes of movement irrespective of the animals'
      location or heading, whereas grid cells in MEC expressed static spatial maps. The
      behavioral correlates of PPC cells switched completely when the same animals ran
      in a spatially structured maze or when they ran similar stereotypic sequences in
      an open arena. Representations in PPC were similar in identical mazes in
      different rooms where grid cells completely realigned their firing fields. The
      data suggest that representations in PPC are determined by the organization of
      actions while cells in MEC are driven by spatial inputs.

PMID- 22365550
TI  - EPAC null mutation impairs learning and social interactions via aberrant
      regulation of miR-124 and Zif268 translation.
AB  - EPAC proteins are the guanine nucleotide exchange factors that act as the
      intracellular receptors for cyclic AMP. Two variants of EPAC genes including
      EPAC1 and EPAC2 are cloned and are widely expressed throughout the brain. But,
      their functions in the brain remain unknown. Here, we genetically delete EPAC1
      (EPAC1(-/-)), EPAC2 (EPAC2(-/-)), or both EPAC1 and EPAC2 genes (EPAC(-/-)) in
      the forebrain of mice. We show that EPAC null mutation impairs long-term
      potentiation (LTP) and that this impairment is paralleled with the severe
      deficits in spatial learning and social interactions and is mediated in a direct
      manner by miR-124 transcription and Zif268 translation. Knockdown of miR-124
      restores Zif268 and hence reverses all aspects of the EPAC(-/-) phenotypes,
      whereas expression of miR-124 or knockdown of Zif268 reproduces the effects of
      EPAC null mutation. Thus, EPAC proteins control miR-124 transcription in the
      brain for processing spatial learning and social interactions.

PMID- 22365552
TI  - Tuned normalization explains the size of attention modulations.
AB  - The effect of attention on firing rates varies considerably within a single
      cortical area. The firing rate of some neurons is greatly modulated by attention
      while others are hardly affected. The reason for this variability across neurons
      is unknown. We found that the variability in attention modulation across neurons
      in area MT of macaques can be well explained by variability in the strength of
      tuned normalization across neurons. The presence of tuned normalization also
      explains a striking asymmetry in attention effects within neurons: when two
      stimuli are in a neuron's receptive field, directing attention to the preferred
      stimulus modulates firing rates more than directing attention to the nonpreferred
      stimulus. These findings show that much of the neuron-to-neuron variability in
      modulation of responses by attention depends on variability in the way the
      neurons process multiple stimuli, rather than differences in the influence of top
      down signals related to attention.

PMID- 22365553
TI  - Sound-driven synaptic inhibition in primary visual cortex.
AB  - Multimodal objects and events activate many sensory cortical areas
      simultaneously. This is possibly reflected in reciprocal modulations of neuronal
      activity, even at the level of primary cortical areas. However, the synaptic
      character of these interareal interactions, and their impact on synaptic and
      behavioral sensory responses are unclear. Here, we found that activation of
      auditory cortex by a noise burst drove local GABAergic inhibition on
      supragranular pyramids of the mouse primary visual cortex, via cortico-cortical
      connections. This inhibition was generated by sound-driven excitation of a
      limited number of cells in infragranular visual cortical neurons. Consequently,
      visually driven synaptic and spike responses were reduced upon bimodal
      stimulation. Also, acoustic stimulation suppressed conditioned behavioral
      responses to a dim flash, an effect that was prevented by acute blockade of
      GABAergic transmission in visual cortex. Thus, auditory cortex activation by
      salient stimuli degrades potentially distracting sensory processing in visual
      cortex by recruiting local, translaminar, inhibitory circuits.

PMID- 22365554
TI  - Only coherent spiking in posterior parietal cortex coordinates looking and
      reaching.
AB  - Here, we report that temporally patterned, coherent spiking activity in the
      posterior parietal cortex (PPC) coordinates the timing of looking and reaching.
      Using a spike-field approach, we identify a population of parietal area LIP
      neurons that fire spikes coherently with 15 Hz beta-frequency LFP activity. The
      firing rate of coherently active neurons predicts the reaction times (RTs) of
      coordinated reach-saccade movements but not of saccades when made alone. Area LIP
      neurons that do not fire coherently do not predict RT of either movement type.
      Similar beta-band LFP activity is present in the parietal reach region but not
      nearby visual area V3d. This suggests that coherent spiking activity in PPC can
      control reaches and saccades together. We propose that the neural mechanism of
      coordination involves a shared representation that acts to slow or speed
      movements together.

PMID- 22365555
TI  - Computerized cognitive training restores neural activity within the reality
      monitoring network in schizophrenia.
AB  - Schizophrenia patients suffer from severe cognitive deficits, such as impaired
      reality monitoring. Reality monitoring is the ability to distinguish the source
      of internal experiences from outside reality. During reality monitoring tasks,
      schizophrenia patients make errors identifying "I made it up" items, and even
      during accurate performance, they show abnormally low activation of the medial
      prefrontal cortex (mPFC), a region that supports self-referential cognition. We
      administered 80 hr of computerized training of cognitive processes to
      schizophrenia patients and found improvement in reality monitoring that
      correlated with increased mPFC activity. In contrast, patients in a computer
      games control condition did not show any behavioral or neural improvements.
      Notably, recovery in mPFC activity after training was associated with improved
      social functioning 6 months later. These findings demonstrate that a serious
      behavioral deficit in schizophrenia, and its underlying neural dysfunction, can
      be improved by well-designed computerized cognitive training, resulting in better
      quality of life.

PMID- 22365556
TI  - Spontaneous healing of Hill-Sachs lesion after arthroscopic bony Bankart repair.

PMID- 22365557
TI  - The influence of superior labrum anterior to posterior (SLAP) repair on restoring
      baseline glenohumeral translation and increased biceps loading after simulated
      SLAP tear and the effectiveness of SLAP repair after long head of biceps
      tenotomy.
AB  - HYPOTHESIS: Biomechanical studies have shown increased glenohumeral translation
      and loading of the long head biceps (LHB) tendon after superior labrum anterior
      to posterior (SLAP) tears. This may explain some of the typical clinical
      findings, including the prevalence of humeral chondral lesions, after SLAP
      lesions. The first hypothesis was that SLAP repair could restore the original
      glenohumeral translation and reduce the increased LHB load after SLAP lesions.
      The second hypothesis was that SLAP repair after LHB tenotomy could significantly
      reduce the increased glenohumeral translation. MATERIALS AND METHODS:
      Biomechanical testing was performed on 21 fresh frozen human cadaveric shoulders
      with an intact shoulder girdle using a sensor-guided industrial robot to apply 20
      N of compression in the joint and 50 N translational force at 0 degrees , 30
      degrees , and 60 degrees  of abduction. LHB loading was measured by a load-cell
      with 5 N and 25 N preload. Type IIC SLAP lesions were created arthroscopically,
      and a standardized SLAP repair was done combined with or without LHB tenotomy.
      RESULTS: No significant difference of glenohumeral translation and increased LHB
      load in SLAP repair compared with the intact shoulder was observed under 5 N and
      25 LHB preload, except for anterior translation under 25 N LHB preload. After LHB
      tenotomy after SLAP lesions, no significant difference of translation was
      observed with or without SLAP repair. CONCLUSIONS: SLAP repair without associated
      LHB tenotomy helps normalize glenohumeral translation and LHB loading. The
      stabilizing effect of the SLAP complex is dependent on the LHB. After biceps
      tenotomy, SLAP repair does not affect glenohumeral translation.

PMID- 22365558
TI  - Treatment of rotator cuff tears in older individuals: a systematic review.
AB  - BACKGROUND: Rotator cuff disease is common in older adults and may compromise
      health status and functional independence. However, little evidence exists to
      guide the treatment of rotator cuff tears (RCTs) in the older patient. This study
      evaluated the evidence regarding treatment of RCTs in patients with a mean age of
      60 years or older. METHODS: PubMed, SCOPUS, Science Citation Index (Web of
      Knowledge), Sport Discus, CINAHL, The Cochrane Controlled Trials registry, podium
      and poster presentations, proceedings, and abstracts from American Academy of
      Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, and
      American Shoulder and Elbow Surgeons were searched for published and unpublished
      studies from 1966 to 2009. Inclusion criteria were English language, level of
      evidence I to III or greater, a full-thickness RCT, and treatment (surgery,
      physical therapy, injections, medications, or observation). Exclusion criteria
      included purely retrospective studies, isolated tears of the subscapularis,
      partial RCTs, revision surgery, and grafting or tendon transfer procedures. The
      blinded studies were independently evaluated using principles in the CONSORT
      (Consolidated Standards of Reporting Trials, 2001) statement and then collated by
      level of evidence and treatment strategy. RESULTS: Eight studies (1 level I, 4
      level II, and 3 level III) evaluated treatment outcomes in patients aged older
      than 60 years. Review of the included operative studies suggests possible
      efficacy with operative intervention. However, heterogeneity of these studies and
      bias did not allow for a valid consensus on the best treatment approach.
      CONCLUSIONS: There is insufficient evidence to suggest efficacy in operative or
      nonoperative treatment of RCTs in older patients. The results presented here
      suggest possible favorable outcomes with operative management of RCTs.

PMID- 22365559
TI  - Wear simulation of reverse total shoulder arthroplasty systems: effect of
      glenosphere design.
AB  - BACKGROUND: Although early results with reverse total shoulder arthroplasty
      (rTSA) have been promising, concern exists about the high reported rates of
      scapular notching and the potential for catastrophic failure of glenoid component
      fixation. Generation of polyethylene wear debris may also contribute to notching
      and osteolysis of the scapula. A testing model for polyethylene wear is currently
      unavailable for reverse shoulder prostheses. The goal of this study was to
      develop a testing protocol using a commercially available hip simulator.
      Component design may also influence the generation of polyethylene debris. It is
      hypothesized that increased polyethylene wear occurs in glenospheres with holes
      in the articulating surface. MATERIALS AND METHODS: Custom fixtures were
      fabricated to simulate both glenohumeral abduction and flexion on a 12-station
      hip wear simulator. Loading profiles for both abduction and flexion were
      alternated every 250,000 cycles for a total of 5 million cycles. Gravimetric
      analysis of humeral cups throughout the test was used to characterize wear.
      Lubricant fluid was collected throughout the test and digested for polyethylene
      particle analysis. RESULTS: Comparisons of volumetric wear rates and total volume
      loss between glenospheres with and without holes and between flexion and
      abduction loading profiles showed similar results. Particle analysis displayed
      fibrillar particles with an equivalent circle diameter of 0.3 +/- .1 MUm and an
      aspect ratio of 2.5 +/- 1.4. CONCLUSIONS: This study represents the first wear
      simulation and particle characterization of reverse shoulder systems. No
      significant difference in wear was reported between glenospheres with and without
      holes.

PMID- 22365560
TI  - Thrombin generation post elective caesarean section: effect of low molecular
      weight heparin.
AB  - INTRODUCTION: Caesarean section (CS) is a significant risk factor for venous
      thromboembolism.. Low molecular weight heparin (LMWH) is commonly used for
      thromboprophylaxis post emergency caesarean delivery. However, no consensus
      exists regarding LMWH thromboprophylaxis following elective caesarean section.
      Measures of thrombin formation may indicate the full anticoagulant activity of
      LMWH in this setting. MATERIALS AND METHODS: Anti-Xa, tissue factor pathway
      inhibitor (TFPI), thrombin anti-thrombin complex (TAT) and endogenous thrombin
      potential (ETP) were measured in twenty healthy women who received 4,500 IU
      tinzaparin 6 hours post CS (CS1), twenty women who received 4,500 IU tinzaparin
      at 10-12 hours post delivery (CS2) and twenty women post spontaneous vaginal
      delivery (SVD). RESULTS: Prior to initiation of LMWH, TAT levels at 6 hours post
      delivery were significantly higher in the CS1 and CS2 groups than the SVD group
      (P<0.002); TAT levels were significantly reduced up to 24 hours post LMWH
      treatment despite declining anti-Xa levels (P<0.001). In CS1, peak thrombin and
      ETP were significantly reduced following LMWH prophylaxis (P<0.0001; P<0.002) and
      reverted to pre-delivery levels 10 hours post LMWH. TFPI levels mirror anti-Xa
      levels during the 24 hours following LMWH treatment in CS1 group with peak levels
      coinciding with peak anti-Xa levels 4 hours post injection. CONCLUSION: In women
      post caesarean section, anti-Xa levels do not reflect the full anticoagulant
      effects of LMWH. In-vivo thrombin production (TAT) is effectively reduced even
      when anti-Xa levels are negligible. LMWH thromboprophylaxis in this healthy
      cohort of patients appears to have a sustained effect in reducing excess thrombin
      production post elective caesarean section.

PMID- 22365561
TI  - Three novel cyclic hexapeptides from Streptomyces alboflavus 313 and their
      antibacterial activity.
AB  - Three novel cyclic hexapeptides, designated NW-G05 (1), NW-G06 (2) and NW-G07
      (3), were isolated from the fermentation broth of Streptomyces alboflavus 313.
      Their structures were elucidated on the basis of extensive spectroscopic
      analysis, MS experiments, and chemical analysis. Their antibacterial activities
      against several strains of bacteria were evaluated by micro-broth dilution
      method. Among these compounds, NW-G06 (2) and NW-G07 (3) displayed highly
      antibacterial activity against gram-positive bacteria, but not gram negative
      ones. However, NW-G05 (1) was not active against all tested microorganisms.

PMID- 22365562
TI  - Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold.
AB  - Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin
      inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were
      prepared as potential dual antithrombotic compounds. Fluorine scan (3
      fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl
      substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4
      difluorobenzyl)amino compound (9i) as the most potent compound with balanced dual
      activity (K(i(Thr))=0.33+/-0.07MUM, IC(50(GP IIb/IIIa))=1.1+/-0.6MUM).

PMID- 22365563
TI  - Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP
      ribose)polymerase-1 inhibitors.
AB  - We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with
      PARP-1 inhibitory activity in the high micromolar range (IC(50) = 5.75 MUM) could
      be transformed into highly active derivatives with only marginal increase in
      molecular weight. Convenient one to two synthetic steps allowed us to explore
      extensive SAR at the 2-, and 5- through 8-positions of the quinazolin-4(3H)-one
      scaffold. Substitutions at the 2- and 8-positions were found to be most favorable
      for improved PARP-1 inhibition. The amino group at 8-position resulted in
      compound 22 with an IC(50) value of 0.76 MUM. Combination of the 8-amino
      substituent with an additional methyl substituent at the 2-position provided the
      most potent compound 31 [8-amino-2-methylquinazolin-4(3H)-one, IC(50) = 0.4 MUM]
      in the present study. Compound 31 inhibited the proliferation of Brca1-deficient
      cells with an IC(50) value of 49.0 MUM and displayed >10-fold selectivity over
      wild type counterparts. Binding models of these derivatives within the active
      site of PARP-1 have further supported the SAR data and will be useful for future
      lead optimization efforts.

PMID- 22365564
TI  - Primary primitive neuroectodermal tumor of the cervix confirmed with molecular
      analysis in a 23-year-old woman: A case report.
AB  - Primitive Neuroectodermal Tumor (PNET) of the genital tract is very rare,
      especially in the cervix. A case report of a young woman with a diagnosis of PNET
      originating from the uterine cervix is presented here. A 23-year-old woman
      presented with abnormal uterine bleeding and sharp lower abdominal pain of two
      months duration. CT and MRI of the abdomen and thorax revealed the presence of a
      large mass in the uterine cervix, enlarged pelvic lymph nodes and broncho
      pulmonary infiltrations with regional nodes. Pathological examination of the
      tumor revealed a malignant neoplasm composed predominantly of small cells,
      immunohistochemically positive for CD99, vimentin and c-Kit. Molecular testing
      demonstrated the expression of EWS/FLI1 fusion transcripts corresponding to the
      t(11;22)(q24;q12) translocation, which confirmed the diagnosis of PNET of the
      uterine cervix. Despite surgical excision and administration of the first cycle
      of adjuvant chemotherapy, the patient died from multiple-organ failure and
      cardiac arrest. PNET arising from the genital tract, especially in the uterine
      cervix, is very rare and presents a diagnostic challenge. A timely confirmation
      with molecular analysis is essential for the diagnosis of such a tumor at an
      unusual site as in the present case.

PMID- 22365565
TI  - Modulation of remifentanil-induced postinfusion hyperalgesia by the beta-blocker
      propranolol in humans.
AB  - Acute and chronic exposure to opioids has been associated with hyperalgesia in
      both animals and humans. A genetic analysis of opioid-induced hyperalgesia in
      mice linked the beta(2)-adrenergic receptor to mechanical sensitization after
      opioid exposure. In humans, expansion of the area of mechanical hyperalgesia
      surrounding an experimentally induced lesion after the cessation of remifentanil
      infusion is a commonly used model of opioid hyperalgesia (remifentanil-induced
      postinfusion hyperalgesia, RPH). The purpose of our translational study was to
      test the hypothesis that the beta-adrenergic receptor antagonist propranolol
      modulates the expression of RPH in humans. This double-blinded, randomized,
      placebo-controlled, crossover study was performed in 10 healthy human volunteers.
      During test sessions, intracutaneous electrical stimulation was used to generate
      areas of secondary mechanical hyperalgesia. The area of this sensitization was
      measured before, during, and after remifentanil infusion. Heat pain sensitivity
      was also followed. During one test session, subjects received propranolol
      infusion. We observed an average increase in the areas of secondary mechanical
      hyperalgesia to 141% of the baseline in subjects infused with remifentanil and
      placebo (P=0.00040). However, when remifentanil infusion was combined with
      propranolol, the area of secondary hyperalgesia after terminating remifentanil
      was not significantly different than the area before beginning the opioid
      infusion (P=0.13). Thermal hyperalgesia was not observed after remifentanil
      infusion. Propranolol infusion at the selected dose had minor hemodynamic
      effects. Concomitant infusion of propranolol with remifentanil prevented the
      expression of RPH. beta-adrenergic receptor blockade may be a useful
      pharmacological strategy for preventing hyperalgesia in patients exposed to
      opioids.

PMID- 22365566
TI  - Direct and fast determination of paclitaxel, morphine and codeine in urine by
      micellar electrokinetic chromatography.
AB  - A micellar electrokinetic chromatography (MEKC) method was developed for the
      determination of paclitaxel, morphine and codeine in human urine from patients
      under cancer treatment. The background electrolyte consisted of a borate buffer
      (pH 9.2; 20 mM) with sodium dodecyl sulfate (60 mM) and 5% MeOH. The applied
      voltage was 25 kV, temperature was 20  degrees C and the sample injection was
      performed in the hydrodynamic mode. All analyses were carried out in a fused
      silica capillary with an internal diameter of 75 MUm and a total length of 57 cm.
      The detection of target compounds was performed at 212 nm. Under these
      conditions, a complete separation of paclitaxel, morphine and codeine was
      achieved in less than 15 min. According to the validation study, the developed
      method was proved to be accurate, precise, sensitive, specific, rugged and
      robust. This method was applied to the analysis of six urines samples from
      different cancer patients undergoing treatment with paclitaxel or/and codeine. In
      all the urine paclitaxel determination were done.

PMID- 22365567
TI  - Quantitative determination of perchlorate in bottled water and tea with online
      solid phase extraction high-performance liquid chromatography coupled to tandem
      mass spectrometry.
AB  - Due to the similarity in ionic radius, perchlorate has been reported to inhibit
      the iodide intake in the thyroid gland, which may lead to low heart rate, weight
      gain, and fatigue. In recent years, the presence of perchlorate in drinking
      water, surface water, soil, and food supplies in the United States has raised a
      great concern on establishing the maximum residue limit (MRL) for perchlorate to
      reduce its possible adverse influence on human health. US EPA currently puts
      perchlorate on the final third Contamination Candidate List (CCL3) and suggests a
      health reference level at 4.9 MUg L-1. The MRL of perchlorate was therefore set
      at 5.0 MUg L-1 by the authors for method validation. In this study, large volume
      injection (up to 1-mL) and online solid phase extraction (SPE) were utilized for
      pre-concentrating perchlorate ions and removing unretained matrix components
      prior to reversed-phase HPLC analysis using ESI-tandem MS under the negative
      mode. After eluting perchlorate from online SPE, 0.1% formic acid solution was
      utilized for isocratic HPLC analysis without any organic solvent. Multiple
      reaction monitoring (MRM) and the internal standard, Cl18O4-, were utilized for
      quantitatively determining perchlorate in bottled water and bottled tea samples.
      Two linear ranges, 0.05-0.50 MUg L-1 and 0.50-10.00 MUg L-1, were established to
      better estimate the residual amounts of perchlorate in bottled water samples with
      a method detection limit (MDL, signal-to-noise ratio of 3) of 0.01 MUg L-1. The
      linear range was 1.50-10.00 MUg L-1 for bottled tea samples with a MDL of 0.5 MUg
      L-1. In addition, the proposed method was further validated based on the EU
      Commission Decision 2002/657/EC, including within-laboratory reproducibility,
      decision limit (CCalpha), and detection capability (CCbeta) for bottled water and
      bottled tea samples. The intra-day/inter-day precision and accuracy as well as
      within-laboratory reproducibility were determined by calculating the relative
      standard deviation (RSD) at three spiked levels (0.5 MRL, 1 MRL, 1.5 MRL). The
      within-laboratory reproducibility (n=18) for both bottled water and bottled tea
      samples, spiked at MRL (5.0 MUg L-1) of ClO4-, was less than 10%. The values of
      CCalpha/CCbeta were reported as 5.43/5.74 MUg L-1 and 5.03/5.75 MUg L-1 for
      bottled water and bottled tea samples, respectively.

PMID- 22365568
TI  - A method for improving the calculation accuracy of acid-base constants by inverse
      gas chromatography.
AB  - In this paper, studies were conducted in order to improve the calculation
      accuracy of acid-base constants measured by inverse gas chromatography. The
      conventional a.(gamma(d)(l))(0.5) parameters of DCM (dichloromethane), TCM
      (trichloromethane), and EtAcet (ethyl acetate) were corrected as 185, 212, and
      235 A(2)(mJ/m(2))(0.5) by analyzing the relationship between a.(gamma(d)(l))(0.5)
      and the boiling temperature of the probe solvents, where a is molecular area and
      gamma(l)(d) is surface dispersive free energy of the probe solvents,
      respectively. To validate the availability of the new a.(gamma(d)(l))(0.5)
      values, the acid-base constants of polystyrene were measured. It was found that
      when the new a.(gamma(d)(l))(0.5) parameters were adopted, the final linear fit
      degree for the plot of -DeltaH(a)(s)/AN* versus DN/AN* was enhanced from 0.993 to
      0.999, and the standard deviation was decreased from 0.344 to 0.156. In addition,
      the availability of general application to improving the calculation accuracy of
      acid-base constants with the new a.(gamma(d)(l))(0.5) parameters was also proved
      with a mathematical justification.

PMID- 22365569
TI  - Dioctyl sulfosuccinate analysis in near-shore Gulf of Mexico water by direct
      injection liquid chromatography-tandem mass spectrometry.
AB  - Dioctyl sulfosuccinate (DOSS) was a major component of the dispersants most used
      in the 2010 Deepwater Horizon Oil Spill incident response. This analytical method
      quantifies salt water DOSS concentrations to a reporting limit of 20 MUg/L, which
      was below the United States Environmental Protection Agency's (U.S. EPA) 40 MUg/L
      DOSS Aquatic Life Benchmark. DOSS in Gulf of Mexico water samples were analyzed
      by direct-injection reversed-phase liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Sample preparation with 50% acetonitrile (ACN) enabled quantitative
      transfer of DOSS and increased DOSS response 20-fold by reducing aggregation.
      This increased sensitivity enabled the detection of a confirmatory transition
      over the calibration range of 10-200 MUg/L. U.S. EPA Region 5 and Region 6
      laboratories analyzed hundreds of near-shore surface Gulf of Mexico water
      samples, none contained more than the 20 ppb reporting limit. The matrix spike
      DOSS/deuterated surrogate (DOSS-D34) correlation of determination varied with
      mobile phase modifier (ammonium formate R(2)=0.95 and formic acid R(2)=0.27).
      Using ammonium formate, DOSS-D34 accurately measured DOSS matrix effect. The near
      shore sodium concentrations varied more than 10,000-fold, but were not strongly
      correlated with DOSS recovery. DOSS detection by LC-MS/MS enabled rapid analysis
      which was valuable in guiding incident response.

PMID- 22365570
TI  - Food prices and blood cholesterol.
AB  - Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High
      cholesterol levels, which are closely related to dietary habits, are a major
      contributor to CVD. In this article, we study whether changes in food prices are
      related to cholesterol levels and whether taxes or subsidies on particular foods
      would be effective in lowering cholesterol levels and, consequently, CVD costs.
      We find that prices of vegetables, processed foods, whole milk and whole grains
      are significantly associated with blood cholesterol levels. Having analyzed the
      costs and benefits of government interventions, we find that a subsidy of
      vegetables and whole grains would be an efficient way to reduce CVD expenditures.

PMID- 22365572
TI  - Origin of blood cells and HSC production in the embryo.
AB  - Hematopoietic stem cells (HSCs) are capable of self-renewal and differentiation
      into all blood cell types. During adult life, they reside in the bone marrow in a
      quiescent state. By contrast, in the growing embryo hematopoiesis is sequentially
      found in several developmental niches. This review provides an overview of the
      still controversial contribution of each of these embryonic sites to the final
      pool of adult HSCs and discusses new insights into the cellular origin and the
      molecular regulation implicated in the generation of blood progenitor cells. A
      better understanding of HSC development during ontogeny is essential to develop
      new strategies to amplify HSCs or to generate them from embryonic stem cells or
      by somatic cell reprogramming.

PMID- 22365571
TI  - [The Alliance for the Prevention of Colorectal Cancer in Spain. A civil
      commitment to society].
AB  - Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and
      women are considered together, and the second leading cause of cancer death.
      Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people
      die from the disease. Epidemiologic estimations for the coming years show a
      significant increase in the number of annual cases. CRC is a perfectly
      preventable tumor and can be cured in 90% of cases if detected in the early
      stages. Population-based screening programs have been shown to reduce the
      incidence of CRC and mortality from the disease. Unless early detection programs
      are established in Spain, it is estimated that in the coming years, 1 out of 20
      men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for
      the Prevention of Colorectal Cancer in Spain is an independent and non-profit
      organization created in 2008 that integrates patients' associations, altruistic
      non-governmental organizations and scientific societies. Its main objective is to
      raise awareness and disseminate information on the social and healthcare
      importance of CRC in Spain and to promote screening measures, early detection and
      prevention programs. Health professionals, scientific societies, healthcare
      institutions and civil society should be sensitized to this highly important
      health problem that requires the participation of all sectors of society. The
      early detection of CRC is an issue that affects the whole of society and
      therefore it is imperative for all sectors to work together.

PMID- 22365573
TI  - Phosducin rs12402521 polymorphism predicts development of hypertension in young
      subjects with overweight or obesity.
AB  - BACKGROUND AND AIMS: The G-protein regulator phosducin has been shown to be
      associated with stress-dependent blood pressure, but whether obesity is a
      modulator of the relationship between phosducin and risk of hypertension is
      unknown. We studied the effect of two phosducin polymorphisms on risk of
      hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants
      from the HARVEST and 287 normal weight (NW) participants. METHODS AND RESULTS:
      Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time
      PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele,
      27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of
      follow-up, 339 subjects developed hypertension. In a Cox multivariable model,
      carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk
      of hypertension. However, increased incidence of hypertension associated with A
      allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob
      individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in
      NW subjects the incidence of hypertension did not differ by genotype (56% in both
      groups). In the whole cohort, there was a significant interaction of phosducin
      genotype with body mass index on the risk of hypertension (p = 0.012). For SNP
      rs6672836 no association was found with incident hypertension. No haplotype
      effect was detected on the risk of hypertension. CONCLUSION: These data suggest
      that phosducin rs12402521 polymorphism is an important genetic predictor of
      obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive
      nonpharmacological measures should be implemented.

PMID- 22365574
TI  - Coarse-grained molecular simulations of large biomolecules.
AB  - Recently, we saw a dramatic increase in the number of researches that rely on
      coarse-grained (CG) simulations for large biomolecules. Here, first, we briefly
      describe recently developed and used CG models for proteins and nucleic acids.
      Balance between structure-based and physico-chemical terms is a key issue. We
      also discuss the multiscale algorithms used to derive CG parameters. Next, we
      comment on the dynamics used in CG simulations with an emphasis on the importance
      of hydrodynamic interactions. We then discuss the pros and cons of CG
      simulations. Finally, we overview recent exciting applications of CG simulations.
      Publicly available tools and software for CG simulations are also summarized.

PMID- 22365575
TI  - How SNARE molecules mediate membrane fusion: recent insights from molecular
      simulations.
AB  - SNARE molecules are the core constituents of the protein machinery that
      facilitate fusion of synaptic vesicles with the presynaptic plasma membrane,
      resulting in the release of neurotransmitter. On a molecular level, SNARE
      complexes seem to play a quite versatile and involved role during all stages of
      fusion. In addition to merely triggering fusion by forcing the opposing membranes
      into close proximity, SNARE complexes are now seen to also overcome subsequent
      fusion barriers and to actively guide the fusion reaction up to the expansion of
      the fusion pore. Here, we review recent advances in the understanding of SNARE
      mediated membrane fusion by molecular simulations.

PMID- 22365576
TI  - Organisation of maternity care and choices of mode of birth: a worldwide view.
AB  - Drawing on the findings from a Cochrane systematic review of midwife-led care vs.
      other models of maternity care, this article discusses maternity organisation of
      care, women's choice of mode of birth and a global trend in reducing normality of
      childbirth. The review included 11 trials involving 12,276 women. The results
      showed that women who received models of midwife led care were less likely to
      experience fetal loss before 24 weeks' gestation, less likely to have regional
      analgesia, less likely to have instrumental birth, less likely to have an
      episiotomy (with no significant differences in perineal lacerations), and were
      more likely to be attended at birth by a known midwife, more likely to have a
      spontaneous vaginal birth, initiate breast feeding and more stated to feel in
      control. In addition, their babies were more likely to have a shorter length of
      hospital stay. No statistically significant differences were observed in fetal
      loss/neonatal death of at least 24 weeks or in overall fetal/neonatal death
      between women who were allocated to the midwifery led care and those in the
      medical led care. In light of these findings, the interrelationship between
      social organisation of maternity care, philosophy of care and choice is explored
      using case examples with high and low rates of caesarean section rates. A
      worldwide overview of vaginal birth and caesarean section rates as indicators of
      normality (and lack of it) is also presented. Questions are raised with regard to
      the fast growing rate of caesarean section rates particularly among middle income
      countries. The rate of caesarean section is twice as much in private settings
      compared to public hospitals in these countries. In conclusion, the importance of
      sharing good practice among countries with particular attention to social
      location of midwifery, mobilisation of consumer groups as well as education of
      maternity health-care professionals and women, in facilitation of an effective
      'informed choice', is highlighted. Areas for further global research on factors,
      which may influence women's choice of mode of birth are debated.

PMID- 22365577
TI  - [Et al].

PMID- 22365578
TI  - Cataract surgery practice patterns in the United States Veterans Health
      Administration.
AB  - To document current cataract surgery practice patterns of ophthalmologists in the
      United States Veterans Health Administration, an anonymous online 27-question
      survey was emailed to the 132 members of the Association of Veterans Affairs
      Ophthalmologists. The results were tabulated in a computerized database and
      analyzed with descriptive statistics. The response rate was 53% (70/132); 89%
      (62/70) of the respondents performed cataract surgery. Sixty percent (36/60) of
      the responding cataract surgeons were full-time employees, and most (85%, 51/60)
      trained residents. Common practices among them included partial coherence
      interferometry for biometry (81%, 47/58), topical anesthesia (57%, 33/58), clear
      corneal incisions (91%, 53/58), and acrylic single-piece intraocular lens (IOL)
      implantation (97%, 56/58). Eighty-three percent (48/58) offered toric IOLs at
      their facilities. These results will help benchmark cataract surgery practice
      patterns in teaching hospitals and facilitate comparison with cataract surgery in
      other settings.

PMID- 22365579
TI  - Combined treatment with flap amputation, phototherapeutic keratectomy, and
      collagen crosslinking in severe intractable post-LASIK atypical mycobacterial
      infection with corneal melt.
AB  - A 23-year-old woman was referred for management of intractable post-laser in situ
      keratomileusis (LASIK) keratitis due to atypical mycobacteria in the left eye.
      Corrected distance visual acuity was 20/20 in the right eye and counting fingers
      at 3 meters in the left eye. Slitlamp examination revealed multiple infiltrates
      in the flap interface and severe corneal stromal melting with thinning. Despite
      maximum antibiotic therapy for 7 days, the keratitis continued to worsen. A
      penetrating keratoplasty (PKP) was scheduled. While waiting for a corneal graft,
      corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A was
      proposed as an alternative treatment. Flap amputation and limited
      phototherapeutic keratotomy (PTK) (10 MUm) were also performed. One week
      postoperatively, all infiltrates and stromal edema had resolved. At 3 months, the
      uncorrected distance visual acuity improved to 20/35. Corneal crosslinking after
      flap amputation and limited PTK was an effective treatment for severe intractable
      post-LASIK keratitis with corneal melting and obviated PKP.

PMID- 22365580
TI  - Comparison of Goldmann applanation and dynamic contour tonometry before and after
      cataract surgery.
AB  - PURPOSE: To validate changes in intraocular pressure (IOP) after
      phacoemulsification with intraocular lens (IOL) implantation without pressure
      lowering surgery in previously unoperated eyes of normal and glaucoma patients.
      SETTING: University Eye Clinic, Otto-von-Guericke-University, Magdeburg, Germany.
      DESIGN: Cohort study. METHODS: The IOP in both eyes of patients was determined by
      Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) 1 to 2
      days before and after uneventful unilateral surgery. Central corneal thickness
      was used to correct raw GAT readings. RESULTS: Of the 50 patients having
      unilateral phacoemulsification, 29 had had cataract extraction in the
      contralateral eye. The mean baseline IOP was 17.4 +/- 4.4 mm Hg (GAT) and 16.6 +/
      2.9 mm Hg (DCT). Postoperatively, the GAT IOP decreased to 16.4 +/- 6.5 mm Hg
      and the DCT IOP increased slightly to 17.1 +/- 4.1 mm Hg. The mean tonometer
      difference (DeltaIOP = GAT - DCT) amounted to DeltaIOP(pre) = +0.75 +/- 2.69 mm
      Hg in phakic eyes and DeltaIOP(post) = -0.70 +/- 3.76 mm Hg in pseudophakic eyes
      (P=.0011). Consistent results were found in pairs of phakic eyes and pseudophakic
      eyes (mean IOP 18.0 +/- 4.8 mm Hg [GAT] and 17.0 +/- 3.3 mm Hg [DCT]). In fellow
      eyes, the mean GAT reading was 13.4 +/- 4.4 mm Hg and the mean DCT value, 14.8 +/
      2.4 mm Hg. DeltaIOP(phakic) was +1.04 +/- 2.75 mm Hg and DeltaIOP(pseudophakic)
      was -1.48 +/- 2.78 mm Hg (P=.00000021). CONCLUSIONS: The GAT IOP readings in
      pseudophakic eyes seemed to be falsely low. Hence, special attention in the
      screening, diagnosis, and management of glaucoma is necessary.

PMID- 22365581
TI  - Dendritic cells and alveolar macrophages mediate IL-13-induced airway
      inflammation and chemokine production.
AB  - BACKGROUND: IL-13 in the airway induces pathologies that are highly
      characteristic of asthma, including mucus metaplasia, airway hyperreactivity
      (AHR), and airway inflammation. As such, it is important to identify the IL-13
      responding cell types that mediate each of the above pathologies. For example, IL
      13's effects on epithelium contribute to mucus metaplasia and AHR. IL-13's
      effects on smooth muscle also contribute to AHR. However, it has been difficult
      to identify the cell types that mediate IL-13-induced airway inflammation.
      OBJECTIVE: We sought to determine which cell types mediate IL-13-induced airway
      inflammation. METHODS: We treated the airways of mice with IL-13 alone or in
      combination with IFN-gamma. We associated the inhibitory effect of IFN-gamma on
      IL-13-induced airway inflammation and chemokine production with cell types in the
      lung that coexpress IL-13 and IFN-gamma receptors. We then evaluated IL-13
      induced responses in CD11c promoter-directed diphtheria toxin receptor-expressing
      mice that were depleted of both dendritic cells and alveolar macrophages and in
      CD11b promoter-directed diphtheria toxin receptor-expressing mice that were
      depleted of dendritic cells. RESULTS: Dendritic cell and alveolar macrophage
      depletion protected mice from IL-13-induced airway inflammation and CCL11, CCL24,
      CCL22, and CCL17 chemokine production. Preferential depletion of dendritic cells
      protected mice from IL-13-induced airway inflammation and CCL22 and CCL17
      chemokine production but not from IL-13-induced CCL11 and CCL24 chemokine
      production. In either case mice were not protected from IL-13-induced AHR and
      mucus metaplasia. CONCLUSIONS: Pulmonary dendritic cells and alveolar macrophages
      mediate IL-13-induced airway inflammation and chemokine production.

PMID- 22365582
TI  - CD27: a new player in the field of common variable immunodeficiency and EBV
      associated lymphoproliferative disorder?

PMID- 22365583
TI  - We call for iCAALL: International Collaboration in Asthma, Allergy and
      Immunology.

PMID- 22365585
TI  - Elevated serum Bcl-2 in children with temporal lobe epilepsy.
AB  - Intractable temporal lobe epilepsy (TLE) is associated with alterations in
      expression of apoptosis-associated signaling molecules in the temporal lobe. Bcl
      2 is an anti-apoptotic molecule which has previously been reported to be raised
      in patient's brain and serum. In the present study we examined serum Bcl-2
      protein levels as a surrogate marker of apoptosis-associated signaling in
      children with non lesional TLE. Serum Bcl-2 levels were found to be higher in
      patients with TLE than controls. The serum level correlated to seizure variables
      including, duration of disease, frequency of seizures, and disease severity. The
      impact of epilepsy on cognition was assessed using total score intelligence
      quotient (IQ). IQ was found to be lower than controls and negatively correlated
      to serum Bcl-2. These findings support serum Bcl-2 levels as a marker of seizure
      burden and cognition in children with epilepsy.

PMID- 22365586
TI  - Early-onset versus typical childhood absence epilepsy; clinical and
      electrographic characteristics.
AB  - PURPOSE: Childhood absence epilepsy (CAE) is characterized by absence attacks
      with stereotyped electrographic discharges. Epidemiologic data concerning early
      onset CAE is scarce. We tried to specifically analyze the early-onset CAE and
      compare it with typical CAE. METHODS: In this retrospective study, all patients
      with a clinical diagnosis of CAE were recruited in the outpatient epilepsy clinic
      at Shiraz University of Medical Sciences from 2008 to 2011. We considered the age
      of onset at four years or earlier as early-onset and above four years as typical
      CAE. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors,
      and EEG findings of all patients were registered routinely. Statistical analyses
      were performed using Chi square and Fisher's Exact tests. RESULTS: Forty-six
      patients were diagnosed as having CAE. Sixteen patients (35%) had early-onset and
      30 (65%) patients had typical CAE. Sex ratio (female to male) in early-onset was
      7:9 and in typical CAE was 19:11 (P=0.2). Generalized tonic-clonic and myoclonic
      seizures were reported in both early-onset and typical CAE. The differences were
      not statistically significant. Epilepsy risk factors were similarly reported in
      both conditions. The EEG findings were similar in both groups. CONCLUSION: We did
      not observe any significant differences between early-onset and typical childhood
      absence epilepsies with respect to the demographic, clinical and
      electroencephalographic characteristics.

PMID- 22365587
TI  - Modeling single versus multiple systems in implicit and explicit memory.
AB  - It is currently controversial whether priming on implicit tasks and
      discrimination on explicit recognition tests are supported by a single memory
      system or by multiple, independent systems. In a Psychological Review article,
      Berry and colleagues used mathematical modeling to address this question and
      provide compelling evidence against the independent-systems approach.

PMID- 22365588
TI  - C-reactive protein (CRP) is a predictor of high medical-care expenditures in a
      community-based elderly population aged 70 years and over: the Tsurugaya project.
AB  - Because CRP is a strong independent predictor of various diseases, it was
      hypothesized that CRP may be a useful predictor or treatment target for medical
      care expenditures. The aim of this study was to investigate the relationship
      between CRP and medical-care expenditures in a community-dwelling elderly
      population. This prospective cohort study was conducted including 925 Japanese
      subjects aged >=70 years. A high-sensitivity CRP assay was used by applying the
      nephelometric method. Hospitalizations, outpatient visits, and expenditures were
      ascertained through computerized linkage with claims lodged between August 2002
      and March 2008 with the Miyagi National Health Insurance (NHI) Association. Since
      medical-care expenditures were not normally distributed, the category of high
      medical-care expenditures (>75th percentile of medical-care expenditures:
      inpatient expenditures >$494/month; outpatient expenditure >$522/month; total
      expenditures >$1103/month) was used to examine the relation of CRP levels with
      medical-care expenditures. Multiple logistic regression analysis was used to
      examine the relationship between CRP cutoff points (low concentrations: <1.0mg/L;
      intermediate concentrations: 1.0-3.0mg/L; or high concentrations: >=3.0 mg/L) and
      medical-care expenditures during 6 year-follow up period. After adjustment for
      potential confounding factors, a positive association of CRP with
      hospitalization, and total expenditures (p for trend=0.03 and 0.02, respectively)
      was found. An elevated baseline CRP level is an independent predictor of
      increases in prospective medical-care expenditures among community-dwelling
      elderly. Further study is required to clarify whether reducing CRP by
      intervention is a cost-effective measure.

PMID- 22365589
TI  - Expert consensus on gender criteria for assessment in medical communication
      education.
AB  - OBJECTIVE: The aim of this study is to develop gender criteria that can be
      included in communication skills assessment in medical education. METHODS: A
      three-round Delphi study was conducted. The invited 59 participants were experts
      in the field of gender medicine education (n = 28) and doctor-patient
      communication (n = 31). Each Delphi round comprised a questionnaire, an analysis,
      and a feedback report. In the first round, gender experts explored gender themes
      in doctor-patient communication from which initial gender criteria were defined.
      The second and third rounds were used to validate the importance and feasibility
      of gender criteria. Consensus was defined as a 75% panel agreement and a mean of
      4 or higher on a 5-point Likert scale. RESULTS: Four gender criteria achieved
      consensus after the third round. The importance of including the gender criteria
      in communication skills assessment was rated consistently higher than its
      feasibility. Gender criteria relating to the patients' perspective, to gathering
      information and to gender and power were considered the most important.
      CONCLUSION: Using a Delphi study, we have developed gender criteria for inclusion
      in communication skills assessment to promote good communication between doctors
      and patients. PRACTICE IMPLICATIONS: Gender influences medical communication.
      Incorporating gender in communication skills assessment may be useful to improve
      the teaching and learning of communication skills.

PMID- 22365590
TI  - Patients' medical knowledge and health counseling: what kind of information helps
      to make communication patient-centered?
AB  - OBJECTIVE: To examine how physicians use information about a patient's background
      knowledge when both anticipating what a patient knows and producing actual
      answers in an email counseling setting. METHODS: A fictitious patient used a
      (high vs. low) level of technical jargon in an email inquiry about diabetes and
      provided explicit information on prior knowledge (high vs. low) through self
      report. Final-year medical students (semi-experts) were asked to gauge the
      patient's knowledge level (Experiment 1) and to produce an answer to the inquiry
      (Experiment 2). A total of N=150 participated in one of the two experiments.
      RESULTS: Information from word usage and self-reports was used differently in the
      two experiments. A patient self-reporting low knowledge was assumed to have less
      background knowledge than one reporting some knowledge about the domain. The
      technicality of the patient's word use influenced the answers: these were more
      technical when the inquiry used technical jargon instead of everyday language.
      CONCLUSION: Knowledge anticipation and communication behavior in email health
      care seem to be guided by different hints regarding the patient, suggesting the
      existence of two separate mechanisms. PRACTICE IMPLICATIONS: Beyond merely
      teaching physicians or health care providers to be aware of the patient's
      knowledge level when formulating a patient-centered response, on-task methods
      should support health care providers during the actual communication phase by
      providing, for instance, metacognitive prompts.

PMID- 22365591
TI  - Prevalence of and influencing factors for chronic headaches among pregnant women.
AB  - OBJECTIVE: To determine the prevalence of headaches and their influencing factors
      among pregnant women. METHODS: A cross-sectional study was conducted from January
      3 to April 29, 2005, with 1357 women receiving routine pregnancy check-ups at the
      obstetric clinics of the community health institutions of Kayseri, Turkey. A
      structured questionnaire and the Zung Depression Scale were used to collect data.
      RESULTS: Overall, 24.6% (95% confidence interval, 22.3%-26.9%) of the
      participants had headaches before pregnancy, whereas only 17.9% (95% confidence
      interval, 15.9%-20.1%) had headaches during pregnancy. Although the headache
      prevalence was lower during than before pregnancy, it was high among the
      participants aged 35 years or older, those who received help in their housework,
      and those who were multiparous. Moreover, the Zung depression score was
      significantly high among those experiencing headaches. CONCLUSION: The
      significant decrease in headache prevalence observed during pregnancy may be the
      result of a pregnancy-specific hormonal status. However, the most significant
      factors influencing the frequency of headaches in the participants were related
      to their socioeconomic status and the severity of depression.

PMID- 22365592
TI  - Superselective embolization for the management of postpancreatectomy hemorrhage:
      a single-center experience in 25 patients.
AB  - PURPOSE: To evaluate the efficacy of superselective embolization in patients with
      late postpancreatectomy hemorrhage (PPH). MATERIALS AND METHODS: Between January
      2002 and July 2010, 25 patients (19 men) with suspected late PPH (> 24 hours
      after the operation) were evaluated. The primary study endpoint was technical
      success, defined as complete angiographic occlusion of the site of hemorrhage.
      Secondary study endpoints were multidetector computed tomography (CT) and
      angiographic findings regarding accurate detection of the site of hemorrhage,
      persistence of hemorrhage, or occurrence of rebleeding during clinical follow-up.
      RESULTS: Multidetector CT was performed before the intervention in 17 (68%)
      patients with detection of hemorrhage in 15 (88%) patients. The site of
      hemorrhage was detected in 23 (92%) of 25 patients by angiography. Four (17%)
      patients required a superselective catheter position. Embolization was attempted
      in all 23 patients with angiographically visible hemorrhage. In three (13%)
      patients, embolization could not be performed because a superselective catheter
      position was not achievable. Technical success was 83% (19 patients). In one
      patient, hemostasis was not achieved by embolization. Minor complications
      occurred in three (13%) patients. No major complications occurred. Three patients
      with technically successful embolization (16%) had a second episode of bleeding
      during follow-up and required repeat embolization 5-23 days after the procedure.
      The 30-day mortality rate was 20%. CONCLUSIONS: Superselective embolization is a
      technically and clinically effective procedure in patients with late PPH.
      Diagnostic angiography should be performed with a superselective microcatheter
      position to detect the bleeding site effectively.

PMID- 22365593
TI  - Prolonged antibiotic prophylaxis in patients with bilioenteric anastomosis
      undergoing percutaneous radiofrequency ablation.
AB  - PURPOSE: To reduce risk of development of a hepatic abscess in patients with
      preexisting bilioenteric anastomosis (BEA) undergoing radiofrequency (RF)
      ablation of hepatic tumors by use of prolonged antibiotic prophylaxis over at
      least 10 days. MATERIALS AND METHODS: Between April 2003 and June 2011, 184
      patients underwent 206 percutaneous RF ablation procedures for hepatic
      malignancies. Eight patients presented with BEA and were treated in 10 sessions
      at 14 tumor locations. These 8 patients were male and ranged in age from 55-73
      years. Median follow-up was 34 months. Antibiotic prophylaxis was given before
      the intervention (n = 9, piperacillin/tazobactam; n = 1, ciprofloxacin). Oral
      antibiotic prophylaxis after the intervention was continued with ciprofloxacin
      for at least 10 days. In four cases, prophylaxis after the intervention was
      extended with additional antibiotics. RESULTS: A liver abscess occurred 22 days
      after 1 of 10 RF ablation sessions in patients with preexisting BEA. The patient
      who developed an abscess presented with a large hepatocellular carcinoma (59 mm *
      54 mm) and underwent transarterial chemoembolization 8 days before RF ablation.
      No hepatic abscess occurred after 196 RF ablation sessions in 176 patients
      without BEA. CONCLUSIONS: Preexisting BEA is a risk factor for formation of
      hepatic abscesses after RF ablation. An antibiotic prophylaxis regimen before the
      intervention and for a prolonged period after the intervention that covers
      anaerobic bacteria for at least 10 days is presented. Combined therapy of
      transarterial chemoembolization and RF ablation increases the risk for
      complications in patients with known BEA.

PMID- 22365594
TI  - Safe and effective treatment of colorectal anastomotic stricture using a well
      defined balloon dilation protocol.
AB  - PURPOSE: To present a well-defined protocol for balloon dilation for colorectal
      anastomotic strictures and evaluate clinical efficacy of the dilation in 42
      patients. MATERIALS AND METHODS: From October 1999 to June 2010, 42 patients (32
      males and 10 females with mean age 52.1 years +/- 16.3) with surgical colorectal
      anastomotic strictures who received transanal balloon dilation using a well
      defined protocol were retrospectively investigated. After the procedure, a water
      soluble contrast media study was performed to detect possible complications.
      Stricture diameter was measured 1 month after balloon dilation. Clinical outcomes
      and recurrence were evaluated with a median follow-up period of 63.7 months.
      RESULTS: There were 47 dilation sessions performed in 42 patients. Technical
      success and clinical success were achieved in all patients. At long-term follow
      up, 36 (85.7%) patients had complete improvement. No complications were observed
      in any patients. Stricture diameter 1 month after the procedure was 8.85 cm +/-
      3.23, which was a significant increase over stricture diameter before the
      procedure of 5.89 cm +/- 2.64 (P < .001), showing increase in diameter by 50.3%.
      Four (9.5%) patients experienced symptomatic recurrence. Stricture diameter of
      the patients with recurrence was considerably larger than stricture diameter of
      other patients (P = .036). CONCLUSIONS: Fluoroscopically guided balloon dilation
      using the protocol described is safe and clinically effective for treatment of
      colorectal anastomotic stricture.

PMID- 22365595
TI  - Elastic stockings or Tubigrip for ankle sprain: a randomised clinical trial.
AB  - BACKGROUND: Ankle sprains are common and generally believed to be benign and self
      limiting. However, a significant proportion of patients with ankle sprains have
      persistent symptoms for months or even years. AIMS: The study aimed to evaluate
      whether elastic stockings improve recovery following ankle sprain. METHODOLOGY:
      All patients within 72 h of ankle sprain were identified in Accident & Emergency
      or the Fracture Clinic. Consenting patients, stratified for sex, were randomised
      to either: (i) Tubigrip or (ii) class II below knee elastic stockings (ESs, Medi
      UK Ltd.) which were fitted immediately and worn until the patient was pain-free
      and fully mobile. The deep veins of the injured legs were imaged by duplex
      Doppler for deep vein thrombosis (DVT) at 4 weeks. Outcome was compared using the
      American Orthopaedic Foot and Ankle Score (AOFAS) and SF12v2 for quality of life.
      RESULTS: In the 36 randomised patients, the mean (95% confidence interval (CI))
      circumference of the injured ankle treated by ES was 23.5 (23-24)cm initially and
      22 (22-23) and 22 (21-22.5)cm at 4 and 8 weeks (p<0.001) compared with 24 (23-25)
      cm initially and 24 (23-25) and 24 (23-24.5) cm using Tubigrip (p<0.001). By 8
      weeks, the mean AOFAS and SF12v2 scores were significantly improved by ES at 99
      (8.1) and 119 (118-121) compared with 88 (11) and 102 (99-107) with Tubigrip
      (p<0.001). Of the 34 duplex images at 4 weeks, none had a DVT. CONCLUSION:
      Elastic compression improves recovery following ankle sprain.

PMID- 22365596
TI  - Occupational amputations in Illinois 2000-2007: BLS vs. data linkage of trauma
      registry, hospital discharge, workers compensation databases and OSHA citations.
AB  - BACKGROUND: Workplace amputation is a widespread, disabling, costly, and
      preventable public health problem. Thousands of occupational amputations occur
      each year, clustering in particular economic sectors, workplaces, and demographic
      groups such as young workers, Hispanics, and immigrants. OBJECTIVES: To identify
      and describe work related amputations amongst Illinois residents that occur
      within Illinois as reported in three legally mandated State databases; to compare
      these cases with those identified through the BLS-Survey of Occupational
      Illnesses and Injuries (SOII); and to determine the extent of direct intervention
      by the Occupational Safety and Health Administration (OSHA) for these injuries in
      the State. METHODS: We linked cases across three databases in Illinois - trauma
      registry, hospital discharge, and workers compensation claims. We describe
      amputation injuries in Illinois between 2000 and 2007, compare them to the BLS
      SOII, and determine OSHA investigations of the companies where amputations
      occurred. RESULTS: There were 3984 amputations identified, 80% fingertips, in the
      Illinois databases compared to an estimated 3637, 94% fingertips, from BLS-SOII.
      Though the overall agreement is close, there were wide fluctuations (over- and
      under-estimations) in individual years between counts in the linked dataset and
      federal survey estimates. No OSHA inspections occurred for these injuries.
      CONCLUSIONS/RECOMMENDATIONS: Increased detection of workplace amputations is
      essential to targeting interventions and to evaluating program effectiveness.
      There should be mandatory reporting of all amputation injuries by employers and
      insurance companies within 24h of the event, and every injury should be
      investigated by OSHA. Health care providers should recognise amputation as a
      public health emergency and should be compelled to report. There should be a more
      comprehensive occupational injury surveillance system in the US that enhances the
      BLS-SOII through linkage with state databases. Addition of industry, occupation,
      and work-relatedness fields to the Electronic Health Record, the Uniform Billing
      form, and national health surveys would allow better capture of occupational
      cases for prevention and for assigning bills to the right payer source.

PMID- 22365597
TI  - New NIH center to streamline translational science.

PMID- 22365598
TI  - Flexing and stretching in nonribosomal Peptide synthetases.
AB  - Re-engineering of nonribosomal peptide synthetase molecular assembly lines has
      been hampered by a lack of detailed knowledge concerning inter-domain substrate
      transfer. Recent structural studies of catalytically relevant domain-domain
      interactions provide valuable insights into this problem (Liu et al., 2011;
      Sundlov et al., 2012 [in this issue of Chemistry & Biology]).

PMID- 22365599
TI  - Exploiting effectors of Rac GTPase.
AB  - Targeting a specific arm of signaling pathways is of great interest. In this
      issue of Chemistry & Biology, Bosco et al. exploit the interactive interface
      between Rac GTPase and its effector p67(phox) to specifically inhibit reactive
      oxygen species production without perturbing other Rac-mediated cellular
      processes.

PMID- 22365600
TI  - Synergy of peptide and sugar in O-GlcNAcase substrate recognition.
AB  - Protein O-GlcNAcylation is an essential reversible posttranslational modification
      in higher eukaryotes. O-GlcNAc addition and removal is catalyzed by O-GlcNAc
      transferase and O-GlcNAcase, respectively. We report the molecular details of the
      interaction of a bacterial O-GlcNAcase homolog with three different synthetic
      glycopeptides derived from characterized O-GlcNAc sites in the human proteome.
      Strikingly, the peptides bind a conserved O-GlcNAcase substrate binding groove
      with similar orientation and conformation. In addition to extensive contacts with
      the sugar, O-GlcNAcase recognizes the peptide backbone through hydrophobic
      interactions and intramolecular hydrogen bonds, while avoiding interactions with
      the glycopeptide side chains. These findings elucidate the molecular basis of O
      GlcNAcase substrate specificity, explaining how a single enzyme achieves cycling
      of the complete O-GlcNAc proteome. In addition, this work will aid development of
      O-GlcNAcase inhibitors that target the peptide binding site.

PMID- 22365601
TI  - Chemical genetic-mediated spatial regulation of protein expression in neurons
      reveals an axonal function for wld(s).
AB  - The degeneration of axons is the underlying pathological process of several
      neurological disorders. The Wallerian degeneration (Wld(S)) slow protein, which
      is primarily nuclear, markedly inhibits axonal degeneration. Contradictory models
      have been proposed to explain its mechanism, including a role in the nucleus,
      where it affects gene transcription, and roles outside the nucleus, where it
      regulates unknown effectors. To determine which pool of Wld(S) accounts for its
      axon-protective effects, we developed a strategy to control the spatial
      expression of proteins within neurons. This strategy couples a chemical genetic
      method to control protein stability with microfluidic culturing. Using neurons
      that are selectively deficient in Wld(S) in axons, we show that the axonal pool
      of Wld(S) is necessary for protection from axon degeneration. These results
      implicate an axonal pathway regulated by Wld(S) that controls axon degeneration.

PMID- 22365603
TI  - Biomembrane interactions reveal the mechanism of action of surface-immobilized
      host defense IDR-1010 peptide.
AB  - Dissecting the mechanism of action of surface-tethered antimicrobial and
      immunomodulatory peptides is critical to the design of optimized anti-infection
      coatings on biomedical devices. To address this, we compared the biomembrane
      interactions of host defense peptide IDR-1010cys (1) in free form, (2) as a
      soluble polymer conjugate, and (3) with one end tethered to a solid support with
      model bacterial and mammalian lipid membranes. Our results show that IDR-1010cys
      in all three distinct forms interacted with bacterial and mammalian lipid
      vesicles, but the extent of the interactions as monitored by the induction of
      secondary structure varied. The enhanced interaction of surface-tethered peptides
      is well correlated with their very good antimicrobial activities. Our results
      demonstrate that there may be a difference in the mechanism of action of surface
      tethered versus free IDR-1010cys.

PMID- 22365602
TI  - Structural and functional investigation of the intermolecular interaction between
      NRPS adenylation and carrier protein domains.
AB  - Nonribosomal peptide synthetases (NRPSs) are modular proteins that produce
      peptide antibiotics and siderophores. These enzymes act as catalytic assembly
      lines where substrates, covalently bound to integrated carrier domains, are
      delivered to adjacent catalytic domains. The carrier domains are initially loaded
      by adenylation domains, which use two distinct conformations to catalyze
      sequentially the adenylation of the substrate and the thioesterification of the
      pantetheine cofactor. We have used a mechanism-based inhibitor to determine the
      crystal structure of an engineered adenylation-carrier domain protein
      illustrating the intermolecular interaction between the adenylation and carrier
      domains. This structure enabled directed mutations to improve the interaction
      between nonnative partner proteins. Comparison with prior NRPS adenylation domain
      structures provides insights into the assembly line dynamics of these modular
      enzymes.

PMID- 22365604
TI  - Interrogating signaling nodes involved in cellular transformations using kinase
      activity probes.
AB  - Protein kinases catalyze protein phosphorylation and thereby control the flow of
      information through signaling cascades. Currently available methods for
      concomitant assessment of the enzymatic activities of multiple kinases in complex
      biological samples rely on indirect proxies for enzymatic activity, such as
      posttranslational modifications to protein kinases. Our laboratories have
      recently described a method for directly quantifying the enzymatic activity of
      kinases in unfractionated cell lysates using substrates containing a
      phosphorylation-sensitive unnatural amino acid termed CSox, which can be
      monitored using fluorescence. Here, we demonstrate the utility of this method
      using a probe set encompassing p38alpha, MK2, ERK1/2, Akt, and PKA. This panel of
      chemosensors provides activity measurements of individual kinases in a model of
      skeletal muscle differentiation and can be readily used to generate
      individualized kinase activity profiles for tissue samples from clinical cancer
      patients.

PMID- 22365605
TI  - Cholesterol catabolism by Mycobacterium tuberculosis requires transcriptional and
      metabolic adaptations.
AB  - To understand the adaptation of Mycobacterium tuberculosis to the intracellular
      environment, we used comprehensive metabolite profiling to identify the
      biochemical pathways utilized during growth on cholesterol, a critical carbon
      source during chronic infection. Metabolic alterations observed during
      cholesterol catabolism centered on propionyl-CoA and pyruvate pools.
      Consequently, growth on this substrate required the transcriptional induction of
      the propionyl-CoA-assimilating methylcitrate cycle (MCC) enzymes, via the Rv1129c
      regulatory protein. We show that both Rv1129c and the MCC enzymes are required
      for intracellular growth in macrophages and that the growth defect of MCC mutants
      is largely attributable to the degradation of host-derived cholesterol. Together,
      these observations define a coordinated transcriptional and metabolic adaptation
      that is required for scavenging carbon during intracellular growth.

PMID- 22365607
TI  - Elucidation of Piericidin A1 biosynthetic locus revealed a thioesterase-dependent
      mechanism of alpha-pyridone ring formation.
AB  - Piericidins are a class of alpha-pyridone antibiotics that inhibit mitochondrial
      respiratory chain and exhibit antimicrobial, antifungal, and antitumor
      activities. Sequential analysis of Streptomyces piomogeues var. Hangzhouwanensis
      genome revealed six modular polyketide synthases, an amidotransferase, two
      methyltransferases, and a monooxygenase for piericidin A1 production. Gene
      functional analysis and deletion results provide overview of the biosynthesis
      pathway. Furthermore, in vitro characterization of the terminal polyketide
      synthase module with the thioesterase domain using beta-ketoacyl substrates was
      performed. That revealed a pathway where the alpha-pyridone ring formation is
      dependent on hydrolysis of the product beta, delta-diketo carboxylic acid by the
      C-terminal thioesterase followed by amidation and cyclization. These findings set
      the stage to investigate unusual enzymatic mechanisms in alpha-pyridone
      antibiotics biosynthesis, provide a foundation for genome mining of alpha
      pyridone antibiotics, and produce analogs by molecular engineering.

PMID- 22365608
TI  - A bacterial lipooligosaccharide that naturally mimics the epitope of the HIV
      neutralizing antibody 2G12 as a template for vaccine design.
AB  - The broadly neutralizing antibody 2G12 binds a fairly conserved cluster of
      oligomannose sugars on the HIV surface glycoprotein gp120, which has led to the
      hypothesis that these sugars pose potential vaccine targets. Here, we present the
      chemical analysis, antigenicity, and immunogenicity of a bacterial
      lipooligosaccharide (LOS) comprised of a manno-oligosaccharide sequence analogous
      to the 2G12 epitope. Antigenic similarity of the LOS to oligomannose was
      evidenced by 2G12 binding to the LOS and the inability of sera elicited against
      synthetic oligomannosides, but incapable of binding natural oligomannose, to bind
      the LOS. Immunization with heat-killed bacteria yielded epitope-specific serum
      antibodies with the capacity to bind soluble gp120. Although these sera did not
      exhibit specific anti-HIV activity, our data suggest that this LOS may find
      utility as a template for the design of glycoconjugates to target HIV.

PMID- 22365606
TI  - Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox)
      signaling axis in inflammation.
AB  - The NADPH oxidase enzyme complex, NOX2, is responsible for reactive oxygen
      species production in neutrophils and has been recognized as a key mediator of
      inflammation. Here, we have performed rational design and in silico screen to
      identify a small molecule inhibitor, Phox-I1, targeting the interactive site of
      p67(phox) with Rac GTPase, which is a necessary step of the signaling leading to
      NOX2 activation. Phox-I1 binds to p67(phox) with a submicromolar affinity and
      abrogates Rac1 binding and is effective in inhibiting NOX2-mediated superoxide
      production dose-dependently in human and murine neutrophils without detectable
      toxicity. Medicinal chemistry characterizations have yielded promising analogs
      and initial information of the structure-activity relationship of Phox-I1. Our
      studies suggest the potential utility of Phox-I class inhibitors in NOX2 oxidase
      inhibition and present an application of rational targeting of a small GTPase
      effector interface.

PMID- 22365609
TI  - TR-FRET-based duplex immunoassay reveals an inverse correlation of soluble and
      aggregated mutant huntingtin in huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder caused by
      the amplification of a polyglutamine stretch at the N terminus of the huntingtin
      protein. N-terminal fragments of the mutant huntingtin (mHtt) aggregate and form
      intracellular inclusions in brain and peripheral tissues. Aggregates are an
      important hallmark of the disease, translating into a high need to quantify them
      in vitro and in vivo. We developed a one-step TR-FRET-based immunoassay to
      quantify soluble and aggregated mHtt in cell and tissue homogenates. Strikingly,
      quantification revealed a decrease of soluble mHtt correlating with an increase
      of aggregated protein in primary neuronal cell cultures, transgenic R6/2, and
      HdhQ150 knock-in HD mice. These results emphasize the assay's efficiency for
      highly sensitive and quantitative detection of soluble and aggregated mHtt and
      its application in high-throughput screening and characterization of HD models.

PMID- 22365610
TI  - Catalytic contributions of key residues in the adenine glycosylase MutY revealed
      by pH-dependent kinetics and cellular repair assays.
AB  - MutY prevent DNA mutations associated with 8-oxoguanine (OG) by catalyzing the
      removal of adenines opposite OG. pH dependence of the adenine glycosylase
      activity establish that Asp 138 of MutY must be deprotonated for maximal activity
      consistent with its role in stabilizing the oxacarbenium ion transition state in
      an S(N)1 mechanism. A cellular OG:A repair assay allowed further validation of
      the critical role of Asp 138. Conservative substitutions of the catalytic
      residues Asp 138 and Glu 37 resulted in enzymes with a range of activity that
      were used to correlate the efficiency of adenine excision with overall OG:A
      repair and suppression of DNA mutations in vivo. The results show that MutY
      variations that exhibit reduced mismatch affinity result in more dramatic
      reductions in cellular OG:A repair than those that only compromise adenine
      excision catalysis.

PMID- 22365611
TI  - In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the
      biosynthesis of nocardicin A.
AB  - Two nonribosomal peptide synthetases (NRPS), NocA and NocB, together comprising
      five modules, are essential for the biosynthesis of the D,L,D configured
      tripeptide backbone of the monocyclic beta-lactam nocardicin A. We report a
      double replacement gene strategy in which point mutations were engineered in the
      two encoding NRPS genes without disruption of the nocABC operon by placing
      selective markers in adjacent genes. A series of mutants was constructed to
      inactivate the thiolation (T) domain of each module and to evaluate an HHxxxDR
      catalytic motif in NocA and an atypical extended histidine motif in NocB. The
      loss of nocardicin A production in each of the T domain mutants indicates that
      all five modules are essential for its biosynthesis. Conversely, production of
      nocardicin A was not affected by mutation of the NocB histidine motif or the
      R828G mutation in NocA.

PMID- 22365612
TI  - Food for patients at nutritional risk: a model of food sensory quality to promote
      intake.
AB  - BACKGROUND & AIMS: The aim was to investigate food sensory quality as experienced
      and perceived by patients at nutritional risk within the context of establishing
      a framework to develop foods to develop foods to promote intake. METHODS:
      Patients at nutritional risk (NRS-2002; food intake <= 75% of requirements) were
      observed at meals in hospital (food choice, hunger/fullness/appetite scores).
      This was followed by a semi-structured interview based on the observations and
      focusing on food sensory perception and eating ability as related to food
      quality. Two weeks post-discharge, a 3-day food record was taken and interviews
      were repeated by phone. Interviews were transcribed, coded, and analysed
      thematically. RESULTS: Patients (N = 22) from departments of gastrointestinal
      surgery, oncology, infectious medicine, cardiology, and hepatology were
      interviewed at meals (N = 65) in hospital (82%) and post-discharge (18%). Food
      sensory perception and eating ability dictated specific food sensory needs (i.e.,
      appearance, aroma, taste, texture, temperature, and variety defining food sensory
      quality to promote intake) within the context of motivation to eat including:
      pleasure, comfort, and survival. Patients exhibited large inter- and intra
      individual variability in their food sensory needs. CONCLUSIONS: The study
      generated a model for optimising food sensory quality and developing user-driven,
      innovative foods to promote intake in patients at nutritional risk.

PMID- 22365614
TI  - The symphony of the ninth: the development and function of Th9 cells.
AB  - CD4+ T helper cells are obligate regulators of inflammatory disease. An expanding
      cadre of T helper (Th) subsets, specialized for promoting particular types of
      inflammation, function through the secretion of a restricted set of cytokines.
      The latest addition to the list of subsets is the Th9 cell that secretes IL-9 as
      a signature cytokine and contributes to several classes of inflammatory disease.
      In this review we focus on recent advances in understanding the development of
      Th9 cells, and how Th9 cells contribute to the orchestration of disease.

PMID- 22365613
TI  - Higher serum concentrations of dietary antioxidants are associated with lower
      levels of inflammatory biomarkers during the year after hip fracture.
AB  - BACKGROUND & AIMS: Chronic inflammation impairs recovery among the 1.6 million
      people who suffer from hip fracture annually. Vitamin E and the carotenoids are
      two classes of dietary antioxidants with profound anti-inflammatory effects, and
      the goal of this study was to assess whether higher post-fracture concentrations
      of these antioxidants were associated with lower levels of interleukin 6 (IL-6)
      and the soluble receptor for tumor necrosis factor-alpha (sTNF-alphaR1), two
      common markers of inflammation. METHODS: Serum concentrations of the dietary
      antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12
      month follow-up visits among 148 hip fracture patients from The Baltimore Hip
      Studies. Generalized estimating equations modeled the relationship between
      baseline and time-varying antioxidant concentrations and inflammatory markers.
      RESULTS: Higher post-fracture concentrations of vitamin E and the carotenoids
      were associated with lower levels of inflammatory markers. Associations were
      strongest at baseline, particularly between the alpha-tocopherol form of vitamin
      E and sTNF-alphaR1 (p = 0.05) and total carotenoids and both sTNF-alphaR1(p =
      0.01) and IL-6 (p = 0.05). Higher baseline and time-varying alpha-carotene and
      time-varying lutein concentrations were also associated with lower sTNF-alphaR1
      at all post-fracture visits (p <= 0.05). CONCLUSIONS: These findings suggest that
      a clinical trial increasing post-fracture intake of vitamin E and the carotenoids
      may be warranted.

PMID- 22365615
TI  - A randomised prospective study of split skin graft donor site dressings: AWBAT
      DTM vs. Duoderm(r).
AB  - OBJECTIVE: To assess patient comfort and wound-healing efficacy of a new, purpose
      designed biosynthetic material (AWBAT-DTM) in the healing of split-skin graft
      donor sites in comparison with our standard dressing, Duoderm((r)). MATERIALS AND
      METHODS: We conducted a prospective randomised controlled trial of donor site
      dressings, comparing AWBAT-DTM with our standard dressing, Duoderm((r)). Patients
      were randomly allocated to have their donor site dressed with one of these
      materials. Outcome measures included pain scores at rest and during dressing
      changes, time to re-epithelialisation, time to discharge, scarring and infection.
      Results were assessed for significance using the Mann-Whitney U-test (non
      parametric data) and the Chi-Square test (parametric data). RESULTS: Fourteen
      patients were recruited with 8 donor sites in each group. The mean pain scores at
      rest and during dressing changes were not found to be significantly different
      between the two groups (P=0.99 and P=0.90 respectively). The median time to re
      epithelialisation was shorter in the Duoderm((r)) group at 11 days compared to 17
      days in the AWBAT-DTM group (P=0.007). The median time to discharge was not
      significantly different (P=0.38). No infection or scarring has been observed.
      CONCLUSIONS: Based on these early results, AWBAT-DTM appears to have slower donor
      site healing and does not provide significant improvements in postoperative pain
      or discharge time compared to Duoderm((r)). There is no evidence at this stage
      that our standard donor site dressing should be changed.

PMID- 22365616
TI  - Treatment outcomes for keloid scar management in the pediatric burn population.
AB  - INTRODUCTION: Keloids scars are challenging problems facing many reconstructive
      surgeons and have proven to be resistant to many treatments. This is evident by
      the broad range of treatments available and implemented with inconsistent
      results. We reviewed our experience to better define the disorder and to evaluate
      the impact of specific treatment options as related to our patient population.
      METHODS: After obtaining Institutional Review Board approval, we examined the
      medical records of pediatric patients who were evaluated at our pediatric burn
      center between 2000 to 2008. All study subjects were identified as having keloid
      scars confirmed by clinical evaluation (raised scar extending beyond the margins
      of the original wound [1,2]). Treatments included excision and grafting [split
      thickness autograft (STAG) or full thickness autograft (FTAG)], excision and
      grafting with steroid injection, excision and primary closure, or excision and
      primary closure with steroid injection. Patients were included only if there was
      follow-up of 12 months or greater. RESULTS: One hundred and ten subjects with a
      diagnosis of a keloid scar were identified. Twenty-six were treated with excision
      and skin grafting and 8 were treated with a steroid and surgery regimen. Of the
      patients treated with surgery and steroids, the treatment varied from an intra
      operative injection to post-operative injections at 6-week intervals. The number
      of injections was determined by the administering surgeon and varied from one to
      three. Clinical end points were determined by the administering surgeon and
      included: (1) no further improvement in scar maturation or (2) absence of
      improvement. Recurrence was defined as return of a raised scar consistent with a
      keloid scar. The recurrence rate was 87.5% for patients treated with surgery and
      steroids and 80.0% for surgery only. This difference was not statistically
      significant. CONCLUSIONS: Our data demonstrate that steroids do not significantly
      decrease recurrence in pediatric burn related keloids as compared to previously
      published series involving non-burn related keloids [3,5]. This further
      emphasizes that burn related keloids respond differently to conventional
      treatments that have proven successful in keloid scars from other mechanisms of
      injury. A consistent and effective treatment algorithm should be implemented in
      treating keloid scars from burn wounds.

PMID- 22365617
TI  - [Use of an empirical antiretroviral treatment depends on the primary resistance
      rate of the human immunodeficiency virus].
AB  - OBJECTIVE: The objective of this study was the analysis of the prevalence and
      type of primary resistance to antiretroviral drugs in patients diagnosed with HIV
      infection, and to determine the most appropriate empirical treatment to obtain a
      virological and immunological response. PATIENTS AND METHODS: An observational
      analysis of patients with a de novo diagnosis of HIV infection during the period
      2008-2010. Clinical, immunological and virological characteristics, including
      genotype analysis of resistance to antiretrovirals, were considered as
      independent variables. The dependent variable was an undetectable HIV viral load
      after six months of treatment. Data are provided as median (interquartile range)
      and absolute number (percentage). RESULTS: Seventy-three patients with a de novo
      diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old;
      prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection:
      13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute
      HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37%
      (n=27) of all patients. The initiation of antiretroviral therapy followed the
      GESIDA recommendations (no therapy: 20 patients;
      tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1
      patient; tenofovir+emtricitabine+protease inhibitors: 5 patients;
      abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the
      follow-up). After starting antiretroviral therapy, the resistance analyses
      detected the existence of primary resistance to antiretrovirals in 12.7%
      (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated
      resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in
      9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%;
      there were no cases of resistance to protease inhibitors. Consequently,
      antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an
      undetectable HIV viral load at 6 months in all of them. The primary resistance to
      antiretrovirals was not related with epidemiological, virological (including
      infection by non B subtype) or immunological variables. CONCLUSIONS: In the
      present study, a change in the epidemiological pattern of de novo diagnosis of
      HIV infection in our area has been observed. The existence of resistance
      mutations in more than 5% of the new cases is noteworthy. This finding must be
      considered in order to establish the rules of empirical treatment in our area.

PMID- 22365618
TI  - [Clinico-epidemiological characteristics of HIV-positive immigrants: study of 371
      cases].
AB  - INTRODUCTION: The number of HIV-positive immigrants have increased in Spain in
      the last few years, and now represent a significant proportion of the epidemic.
      Our objective is to describe the clinico-epidemiological characteristics of HIV
      positive immigrants seen in a specialist unit in Madrid. MATERIAL AND METHODS:
      Retrospective study. Every patient born in a country other than Spain and
      attended an HIV Unit in Madrid between 1992 and 2009 was included. RESULTS: Of
      the 371 patients included, 53.1% were Latin Americans, 24.5% Sub-Saharan
      Africans, and 22.4% others), and 60% were males. Immigrants represented 0.3% of
      new patients in 1992 and rose to 49.2% in 2009. The principal reason for HIV
      testing had been pregnancy/delivery among women (32.7%) and having a category-B
      disease among men (17.4%). Sexual transmission accounted for 92% of patients.
      Tuberculosis was the principal AIDS-diagnosing illness. Respectively 90%, 7.7%,
      60%, 26.7%, 96% and 95% of patients had an IgG for HAV, HCV, Toxoplasma,
      Treponema, CMV and VZV. VHB-Ags+: 5.4%; PPD+: 17%. At least one syphilis episode
      was recorded in 62% of the men who have sex with men (MSM). Prevalence of HLA
      B5701 was 6%, 0.9% and 3.8% in Caucasians, Amerindians and Afro-Americans,
      respectively. CONCLUSIONS: Immigrants represent a significant proportion of new
      HIV-positive patients. It is a very heterogeneous group according to their
      clinical and epidemiological characteristics.

PMID- 22365619
TI  - The DWEYS peptide in systemic lupus erythematosus.
AB  - Current therapies for treating systemic lupus erythematosus (SLE) mainly rely
      upon nonspecific and toxic immunosuppression by corticosteroids and cytotoxics.
      Although biologics hold promise, many agents have yet to prove clinical
      efficiency in controlled trials, with further limitations related to safety and
      cost. The primary self-specificity in SLE is double-stranded (ds) DNA. Studying
      anti-dsDNA antibodies in animal models of lupus and SLE patients identified a
      neurotoxic and nephrotoxic subset, including the nephritogenic mouse monoclonal
      anti-dsDNA antibody R4 that crossreacts with a sequence present in subunits of
      the N-methyl-d-aspartate receptor. In this review, anti-dsDNA antibodies as a
      pathogenic factor in SLE and recent efforts for the creation of highly specific,
      nontoxic therapeutics against an extremely pathogenic subset of such antibodies
      is discussed.

PMID- 22365620
TI  - Relative importance of hip and sacral pain among long-term gynecological cancer
      survivors treated with pelvic radiotherapy and their relationships to mean
      absorbed doses.
AB  - PURPOSE: To investigate the relative importance of patient-reported hip and
      sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its
      relationship to the absorbed doses in these organs. METHODS AND MATERIALS: We
      used data from a population-based study that included 650 long-term gynecological
      cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in
      Sweden with a median follow-up of 6 years (range, 2-15) and 344 population
      controls. Symptoms were assessed through a study-specific postal questionnaire.
      We also analyzed the hip and sacral dose-volume histogram data for 358 of the
      survivors. RESULTS: Of the survivors, one in three reported having or having had
      hip pain after completing RT. Daily pain when walking was four times as common
      among the survivors compared to controls. Symptoms increased in frequency with a
      mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the
      sacrum. Sacral pain also affected their walking ability and tended to increase
      with a mean absorbed dose >42.5 Gy. CONCLUSIONS: Long-term survivors of
      gynecological cancer treated with pelvic RT experience hip and sacral pain when
      walking. The mean absorbed dose was significantly related to hip pain and was
      borderline significantly related to sacral pain. Keeping the total mean absorbed
      hip dose below 37.5 Gy during treatment might lower the occurrence of long
      lasting pain. In relation to the controls, the survivors had a lower occurrence
      of pain and pain-related symptoms from the hips and sacrum compared with what has
      previously been reported for the pubic bone.

PMID- 22365621
TI  - Clinical behaviors and outcomes for adenocarcinoma or adenosquamous carcinoma of
      cervix treated by radical hysterectomy and adjuvant radiotherapy or
      chemoradiotherapy.
AB  - PURPOSE: To compare clinical behaviors and treatment outcomes between patients
      with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma
      (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant
      radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS:
      A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and
      116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The
      indications for RT/CCRT were deep stromal invasion, positive resection margin,
      parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was
      administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with
      presence of parametrial invasion or LN metastasis were stratified into a high
      risk group, and the rest into an intermediate-risk group. The patterns of failure
      and factors influencing survival were evaluated. RESULTS: The treatment failed in
      39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free
      survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p
      = 0.000). Distant metastasis was the major failure pattern in both groups. After
      multivariate analysis, prognostic factors for local recurrence included younger
      age, parametrial invasion, AC/ASC histology, and positive resection margin; for
      distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC
      histology. Compared with SCC patients, those with AC/ASC had higher local relapse
      rates for the intermediate-risk group but a higher distant metastasis rate for
      the high-risk group. Postoperative CCRT tended to improve survival for
      intermediate-risk but not for high-risk AC/ASC patients. CONCLUSIONS:
      Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for
      cervical cancer patients treated by RH and postoperative RT. Concurrent
      chemoradiotherapy could improve survival for intermediate-risk, but not
      necessarily high-risk, AC/ASC patients.

PMID- 22365622
TI  - Dosimetric impact of breathing motion in lung stereotactic body radiotherapy
      treatment using intensity modulated radiotherapy and volumetric modulated arc
      therapy [corrected].
AB  - PURPOSE: The objective of this study was to investigate the influence of tumor
      motion on dose delivery in stereotactic body radiotherapy (SBRT) for lung cancer,
      using fixed field intensity- modulated radiotherapy (IMRT) and volumetric
      modulated arc therapy (VMAT). METHODS AND MATERIALS: For each of 10 patients with
      stage I/II non-small-cell pulmonary tumors, a respiration-correlated four
      dimensional computed tomography (4DCT) study was carried out. The internal target
      volume was delineated on the maximum intensity projection CT, which was
      reconstructed from the 4DCT dataset. A 5-mm margin was used for generation of the
      planning target volume. VMAT and five-field IMRT plans were generated using
      Pinnacle(3) SmartArc and direct machine parameter optimization, respectively. All
      plans were generated for an Elekta Synergy linear accelerator using 6-MV photons.
      Simulation was performed to study the interplay between multileaf collimator
      (MLC) sequences and target movement during the delivery of VMAT and IMRT. For
      each plan, 4D dose was calculated using deformable image registration of the 4DCT
      images. Target volume coverage and doses to critical structures calculated using
      4D methodology were compared with those calculated using 3D methodology. RESULTS:
      For all patients included in this study, the interplay effect was found to
      present limited impact (less than 1% of prescription) on the target dose
      distribution, especially for SBRT, in which fewer fractions (three fractions) are
      delivered. Dose to the gross tumor volume (GTV) was, on average, slightly
      decreased (1% of prescription) in the 4D calculation compared with the 3D
      calculation. The motion impact on target dose homogeneity was patient-dependent
      and relatively small. CONCLUSIONS: Both VMAT and IMRT plans experienced
      negligible interplay effects between MLC sequence and tumor motion. For the most
      part, the 3D doses to the GTV and critical structures provided good
      approximations of the 4D dose calculations.

PMID- 22365623
TI  - The impact of body mass index on heterotopic ossification.
AB  - PURPOSE: To analyze the impact of different body mass index (BMI) as a surrogate
      marker for heterotopic ossification (HO) in patients who underwent surgical
      repair (SR) for displaced acetabular fractures (DAF) followed by radiation
      therapy (RT). METHODS AND MATERIALS: This is a single-institution retrospective
      study of 395 patients. All patients underwent SR for DAF followed by RT +/-
      indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The
      patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25
      29.9, and >30. The end point of this study was to evaluate the efficacy of RT +/-
      indomethacin in preventing HO in patients with different BMI. RESULTS: Analysis
      of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6
      patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of
      117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression
      analysis showed that the correlation between odds of HO and BMI is significant, p
      < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO
      increased. The risk of developing HO is 1.0* (10%) more likely among those with
      higher BMI compared with those with lower BMI. For a one-unit increase in BMI the
      log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no
      significant difference among all other factors and HO (e.g., indomethacin, race,
      gender). CONCLUSIONS: Despite similar surgical treatment and prophylactic
      measures (RT +/- indomethacin), the risk of HO appears to significantly increase
      in patients with higher BMI after DAF. Higher single-fraction doses or multiple
      fractions and/or combination therapy with nonsteroidal inflammatory drugs may be
      of greater benefit to these patients.

PMID- 22365624
TI  - Live-cell imaging visualizes frequent mitotic skipping during senescence-like
      growth arrest in mammary carcinoma cells exposed to ionizing radiation.
AB  - PURPOSE: Senescence-like growth arrest in human solid carcinomas is now
      recognized as the major outcome of radiotherapy. This study was designed to
      analyze cell cycle during the process of senescence-like growth arrest in mammary
      carcinoma cells exposed to X-rays. METHODS AND MATERIALS: Fluorescent
      ubiquitination-based cell cycle indicators were introduced into the human mammary
      carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell
      imaging for up to 5 days after exposure to 10 Gy of X-rays. RESULTS: Live-cell
      imaging revealed that cell cycle transition from G2 to G1 phase without mitosis,
      so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2
      irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear
      accumulation of mKO(2)-hCdt1 as well as cyclin E, which was inversely correlated
      to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More
      than 90% of cells skipping mitosis were persistently arrested in G1 phase and
      showed positive staining for the senescent biochemical marker, which is
      senescence-associated beta-galactosidase, indicating induction of senescence-like
      growth arrest accompanied by mitotic skipping. While G2 irradiation with higher
      doses of X-rays induced mitotic skipping in approximately 80% of cells,
      transduction of short hairpin RNA (shRNA) for p53 significantly suppressed
      mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is
      associated with p53 function. CONCLUSIONS: The present study found the pathway of
      senescence-like growth arrest in G1 phase without mitotic entry following G2
      irradiation.

PMID- 22365625
TI  - Clinical outcomes in international federation of gynecology and obstetrics stage
      IA endometrial cancer with myometrial invasion treated with or without
      postoperative vaginal brachytherapy.
AB  - PURPOSE: To assess the clinical outcomes of patients with Stage IA endometrial
      cancer with myometrial invasion treated with postoperative vaginal brachytherapy
      (VBT) with those who received no adjuvant therapy (NAT). METHODS AND MATERIALS:
      All patients treated with hysterectomy for endometrial cancer at Northwestern
      Memorial Hospital between 1978 and 2005 were identified. Those patients with
      Stage IA disease with myometrial invasion who were treated with VBT alone or NAT
      were identified and included in the present analysis. RESULTS: Of 252 patients
      with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who
      met the inclusion criteria, 169 underwent VBT and 83 received NAT. The median
      follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the
      VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In
      the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively.
      Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and
      5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year
      recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT
      group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT
      patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal
      recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%).
      Recurrences developed 2-102 months after surgical treatment. Two of the four
      vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation
      toxicity was noted. CONCLUSIONS: The use of postoperative VBT in patients with
      Stage I endometrial cancer with <50% myometrial invasion yielded excellent
      vaginal disease control and disease-free survival, with minimal toxicity.

PMID- 22365626
TI  - Acute cardiac impairment associated with concurrent chemoradiotherapy for
      esophageal cancer: magnetic resonance evaluation.
AB  - PURPOSE: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT)
      for esophageal cancer. METHODS AND MATERIALS: This prospective study was approved
      by the institutional review board, and written informed consent was obtained from
      all participants. The left ventricular function (LVF) of 31 patients with
      esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was
      evaluated using cardiac cine magnetic resonance imaging. The patients were
      classified into two groups according to mean LV dose. The parameters related to
      LVF were compared between before and during (40 Gy) or between before and after
      CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios
      (during/before CCRT, after/before CCRT) were also compared between the groups
      with a t test. Data were expressed as mean +/- SE. RESULTS: In the low LV-dose
      group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased
      significantly (before vs. during vs. after CCRT; 62.7% +/- 2.98% vs. 59.8% +/-
      2.56% vs. 60.6% +/- 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV
      dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1
      +/- 2.93 vs. 57.0 +/- 3.23 mL/m(2)), LV stroke volume index (38.6 +/- 1.56 vs.
      29.9 +/- 1.60 mL/m(2)), and LV ejection fraction (56.9% +/- 1.79% vs. 52.8% +/-
      1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased
      significantly (before vs. during vs. after CCRT; 66.8 +/- 3.05 vs. 72.4 +/- 4.04
      vs. 85.4 +/- 3.75 beats per minute, p < 0.01). Left ventricle wall motion
      decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after
      CCRT; 6.64 +/- 0.54 vs. 4.78 +/- 0.43 vs. 4.79 +/- 0.50 mm), 9 (6.88 +/- 0.45 vs.
      5.04 +/- 0.38 vs. 5.27 +/- 0.47 mm), and 10 (9.22 +/- 0.48 vs. 8.08 +/- 0.34 vs.
      8.19 +/- 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke
      volume index, wall motion in segment 9, and heart rate showed significant
      difference (p < 0.05) after CCRT between the groups. CONCLUSIONS: Concurrent
      chemoradiotherapy for esophageal cancer impairs LVF from an early treatment
      stage. This impairment is prominent in patients with high LV dose.

PMID- 22365627
TI  - Evaluation of the accuracy of a 3D surface imaging system for patient setup in
      head and neck cancer radiotherapy.
AB  - PURPOSE: To evaluate the accuracy of three-dimensional (3D) surface imaging
      system (AlignRT) registration algorithms for head-and-neck cancer patient setup
      during radiotherapy. METHODS AND MATERIALS: Eleven patients, each undergoing six
      repeated weekly helical computed tomography (CT) scans during treatment course
      (total 77 CTs including planning CT), were included in the study. Patient surface
      images used in AlignRT registration were not captured by the 3D cameras; instead,
      they were derived from skin contours from these CTs, thereby eliminating issues
      with immobilization masks. The results from surface registrations in AlignRT
      based on CT skin contours were compared to those based on bony anatomy
      registrations in Pinnacle(3), which was considered the gold standard. Both rigid
      and nonrigid types of setup errors were analyzed, and the effect of tumor
      shrinkage was investigated. RESULTS: The maximum registration errors in AlignRT
      were 0.2 degrees  for rotations and 0.7 mm for translations in all directions.
      The rigid alignment accuracy in the head region when applied to actual patient
      data was 1.1 degrees , 0.8 degrees , and 2.2 degrees  in rotation and 4.5, 2.7,
      and 2.4 mm in translation along the vertical, longitudinal, and lateral axes at
      90% confidence level. The accuracy was affected by the patient's weight loss
      during treatment course, which was patient specific. Selectively choosing surface
      regions improved registration accuracy. The discrepancy for nonrigid registration
      was much larger at 1.9 degrees , 2.4 degrees , and 4.5 degrees  and 10.1, 11.9,
      and 6.9 mm at 90% confidence level. CONCLUSIONS: The 3D surface imaging system is
      capable of detecting rigid setup errors with good accuracy for head-and-neck
      cancer. Further investigations are needed to improve the accuracy in detecting
      nonrigid setup errors.

PMID- 22365628
TI  - Fast arc delivery for stereotactic body radiotherapy of vertebral and lung
      tumors.
AB  - PURPOSE: Flattening filter-free (FFF) beams with higher dose rates and faster
      delivery are now clinically available. The purpose of this planning study was to
      compare optimized non-FFF and FFF RapidArc plans for stereotactic body
      radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. METHODS
      AND MATERIAL: Ten patients with peripheral lung tumors and 10 with vertebral
      metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10
      MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs
      at risk (OAR), number of monitor units (MU), and beam delivery times were
      assessed. GafChromic EBT2 film measurements of FFF plans were performed to
      compare calculated and delivered dose distributions. RESULTS: No major dosimetric
      differences were seen between the two delivery techniques. For lung SBRT plans,
      conformity indices and OAR doses were similar, although the average MU required
      were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV
      coverage, with no significant differences in OAR doses. Average beam delivery
      times were reduced by a factor of up to 2.5, with all FFF fractions deliverable
      within 4 min. Measured FFF plans showed high agreement with calculated plans,
      with more than 99% of the area within the region of interest fulfilling the
      acceptance criterion. CONCLUSION: The higher dose rate of FFF RapidArc reduces
      delivery times significantly, without compromising plan quality or accuracy of
      dose delivery.

PMID- 22365629
TI  - The use of radiation therapy appears to improve outcome in patients with
      malignant primary tracheal tumors: a SEER-based analysis.
AB  - PURPOSE: To conduct a matched pair analysis assessing the impact of radiotherapy
      (RT) in patients with resectable and unresectable primary malignant tracheal
      tumors using Surveillance, Epidemiology and End Results (SEER) database. PATIENTS
      AND METHODS: The SEER registry was used to identify every patient (or "case") who
      received RT between 1988 and 2007 for primary malignant tracheal tumors, and to
      search for corresponding "controls" (not treated with RT), with the same
      prognostic and treatment factors (surgery on the trachea, disease extension,
      histology, and gender). Overall survival (OS) was calculated with the Kaplan
      Meier methods. Results of OS and cumulative incidence of death from tracheal
      cancer in the cases and controls, and in various subsets, were compared using log
      rank and Gray's tests. RESULTS: Two hundred fifty-eight patients who received RT
      were identified, and 78 of these had appropriate matched controls identified,
      forming the basis of this analysis. In the 78 (+RT) cases, the median follow-up
      was 60 months (range, 10-192) in the survivors vs. 55 months (range, 2-187) in
      the controls (no-RT group). Patients in RT group had significantly better OS, and
      a lower cumulative incidence of death from tracheal cancer than no-RT patients (p
      < 0.05). Treatment with radiation was associated with improved survival in
      patients with squamous cell histology [p < 0.0001], regional disease extension [p
      = 0.030], or those that did not undergo resection [p = 0.038]. There were four
      deaths in RT group and three in no-RT group attributed to cardiac and respiratory
      causes. CONCLUSION: Our data suggest a survival benefit for the use of RT broadly
      for all patients with tracheal cancer. Nevertheless, the retrospective nature of
      this observational study limits its interpretation.

PMID- 22365630
TI  - Dosimetric verification using monte carlo calculations for tissue heterogeneity
      corrected conformal treatment plans following RTOG 0813 dosimetric criteria for
      lung cancer stereotactic body radiotherapy.
AB  - PURPOSE: The recently activated Radiation Therapy Oncology Group (RTOG) studies
      of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer
      (NSCLC) require tissue density heterogeneity correction, where the high and
      intermediate dose compliance criteria were established based on superposition
      algorithm dose calculations. The study was aimed at comparing superposition
      algorithm dose calculations with Monte Carlo (MC) dose calculations for SBRT for
      NSCLC and to evaluate whether compliance criteria need to be adjusted for MC dose
      calculations. METHODS AND MATERIALS: Fifteen RTOG 0236 study sets were used. The
      planning tumor volumes (PTV) ranged from 10.7 to 117.1 cm(3). SBRT conformal
      treatment plans were generated using XiO (CMS Inc.) treatment planning software
      with superposition algorithm to meet the dosimetric high and intermediate
      compliance criteria recommended by the RTOG 0813 protocol. Plans were
      recalculated using the MC algorithm of a Monaco (CMS, Inc.) treatment planning
      system. Tissue density heterogeneity correction was applied in both calculations.
      RESULTS: Overall, the dosimetric quantities of the MC calculations have larger
      magnitudes than those of the superposition calculations. On average, R(100%)
      (ratio of prescription isodose volume to PTV), R(50%) (ratio of 50% prescription
      isodose volume to PTV), D(2 cm) (maximal dose 2 cm from PTV in any direction as a
      percentage of prescription dose), and V(20) (percentage of lung receiving dose
      equal to or larger than 20 Gy) increased by 9%, 12%, 7%, and 18%, respectively.
      In the superposition plans, 3 cases did not meet criteria for R(50%) or D(2 cm).
      In the MC-recalculated plans, 8 cases did not meet criteria for R(100%), R(50%),
      or D(2 cm). After reoptimization with MC calculations, 5 cases did not meet the
      criteria for R(50%) or D(2 cm). CONCLUSIONS: Results indicate that the dosimetric
      criteria, e.g., the criteria for R(50%) recommended by RTOG 0813 protocol, may
      need to be adjusted when the MC dose calculation algorithm is used.

PMID- 22365632
TI  - Oxytocin and pair bonding: on possible influences during the life course.

PMID- 22365633
TI  - Effect of natural organic matter on aggregation behavior of C60 fullerene in
      water.
AB  - The stability of C(60) fullerene particles in water affects its mobility,
      bioavailability, and toxicity to organisms. Natural organic matters (NOMs) have
      pronounced effects on the aggregation behavior of C(60) fullerene. This study was
      to examine the effects of NOM structural properties on the aggregation behavior
      of fullerene water suspension (FWS). Fulvic acid (FA), tannic acid (TA), and two
      structurally different humic acids (HA1 and HA7) were studied. HA1 and HA7 were
      sequentially extracted HAs, where HA7 was more hydrophobic than HA1 and had a
      higher molecular weight. Aggregation was induced by addition of varying amounts
      of Ca(2+) to the FWS with 2 mg/L of each NOM. The absolute value of zeta
      potential |zeta| of pure FWS increased after addition of any type of NOM.
      Addition of Ca(2+) to the FWS+NOM system decreased |zeta| of fullerene almost
      uniformly for all types of NOM. FWS critical coagulation concentration (CCC) was
      equal to 14.5, 6.5, 5.4, and 3.7 mM Ca(2+) for HA7, HA1, FA, and TA,
      respectively. The order of increasing CCCs was positively correlated to the NOMs
      molecular weight and negatively to their polarity. A nearly constant zeta for
      FWS+NOM system at a wide range of Ca(2+) concentrations suggested the steric
      stability rather than electrostatic one. This study highlighted the role of NOM
      in the fate of manufactured nanoparticles in the environment and linked the
      structural properties of NOM to their interaction with manufactured
      nanoparticles.

PMID- 22365634
TI  - Oscillations in the capacitance of a nanopore containing an electrolyte due to
      pore width and nonzero size ions.
AB  - Jiang, Jin, and Wu (Nano Lett., 11 (2011), pp. 5373-5377) have reported the
      results of a density functional theory (DFT) study of the capacitance of a
      nanopore containing an electrolyte consisting of charged hard spheres of equal
      diameter and charge. They find that the capacitance of the nanopore and
      electrolyte oscillates. The 'period' of the oscillations is of the order of the
      ionic diameter. Intuitively, the capacitance should tend to zero when the pore
      diameter is too small to accommodate the electrolyte ions and, thus, would
      contains no charge. A superficial glance at their table of contents figure might
      lead one to think that this does not occur in their calculation. However, they do
      not report results for exceedingly small pore diameters. In order to gain insight
      into their results, the Poisson-Boltzmann (PB) theory, which does not account for
      the diameter, is examined briefly. Unsurprisingly, the PB capacitance decreases
      monotonically to zero as the pore diameter decreases. The effect of a nonzero ion
      diameter is included in a semi-empirical manner by appealing to the results of
      the mean spherical approximation (MSA). The resulting capacitance oscillates and
      is qualitatively similar to the DFT results; it is zero at small pore diameter.

PMID- 22365631
TI  - Genome-wide association study of temperament in bipolar disorder reveals
      significant associations with three novel Loci.
AB  - BACKGROUND: The many attempts to identify genes for bipolar disorder (BD) have
      met with limited success, which has generally been attributed to genetic
      heterogeneity and small gene effects. However, it is also possible that the
      categorical phenotypes used in genetic studies of BD are not the most informative
      or biologically relevant. Although quantitative phenotypes provide an alternative
      to categorical phenotypes based on diagnosis, they have not been fully exploited
      in BD genetics due to the lack of accessible biological measures. We have
      explored aspects of temperament as quantitative phenotypes that might define
      subtypes of BD with different clinical features and courses of illness.
      Temperament is a heritable personality factor that establishes the baseline level
      of reactivity, mood, and energy of a person. METHODS: We have performed a genome
      wide association study with genotype data from the Bipolar Genome Study and 1263
      bipolar subjects that had completed the Temperament Evaluation of Memphis, Pisa,
      Paris, and San Diego Autoquestionnaire (TEMPS-A). The TEMPS-A is designed to
      assess lifelong, milder aspects of bipolar symptomatology and defines five
      temperaments: hyperthymic, dysthymic, cyclothymic, irritable, and anxious.
      RESULTS: The irritable temperament produced the most significant result with a
      genome-wide significant p value of 1.7 * 10(-8) on chromosome 1. The hyperthymic
      temperament produced additional genome-wide significant p values of 4.1 * 10(-8)
      and 2.1 * 10(-8) on chromosomes 12 and 22, respectively. CONCLUSIONS: These
      results suggest that aspects of temperament might define subtypes of BD that are
      more clinically and genetically homogenous, which might aid in the identification
      of predisposing genetic variants.

PMID- 22365635
TI  - Catalytic reduction of NO with decomposed methanol on alumina-supported Mn-Ce
      catalysts.
AB  - A series of manganese-ceria supported on alumina catalysts with various Mn/Ce
      ratios are investigated in both methanol decomposition to CO and hydrogen and SCR
      of NO(x) with CO. The study is aimed at the potential application of both
      reactions in integrated devices, where NO(x) is reduced with the products of the
      decomposed methanol. The samples are characterized by nitrogen physisorption,
      XRD, TEM, XPS, UV-Vis, and TPR. It was established that manganese-ceria supported
      on alumina catalysts are perspective in both methanol decomposition and NO
      reduction at temperatures above 723 K, which are typical for exhausted gases from
      the vehicles and some stationary stations. The best catalytic activity and
      selectivity to the desired products under these conditions was found for the
      samples with Mn/Mn+Ce ratio of 0.5 and 0.7. This superior catalytic performance
      is related to the formation of mixed valence Mn(3+)/Ce(4+) and Mn(4+)/Ce(3+)
      active sites.

PMID- 22365636
TI  - Synthesis and properties of Au-Fe3O4 heterostructured nanoparticles.
AB  - Au-Fe(3)O(4) composite nanoparticles have received much research interest due to
      their promising biomedical applications. In this work, Au-Fe(3)O(4) composites
      with well-defined dimer-like nanostructure were synthesized via thermal
      decomposition route. The surfactant 1,2-hexandicandiol has proved to be critical
      for the formation of the Au-Fe(3)O(4) hetero-dimers. The hetero-dimers production
      yield could be significantly improved to be 90% when the 1,2-hexandicandiol
      concentration was optimized at 0.6 M. The obtained Au-Fe(3)O(4) hetero-dimers
      possess dual-functionalities of plasmon resonance and magnetization. Moreover,
      the Fe(3)O(4) domain of the hetero-dimers can be tuned readily by adjusting the
      molar ratio between Fe and Au sources. Furthermore, it was demonstrated that
      these Au-Fe(3)O(4) hetero-dimers could be further developed into star-like Au
      Fe(3)O(4) nanoparticles which showed plasmon absorption at NIR region.

PMID- 22365637
TI  - Synthesis of microporous eskolaite from Cr(VI) using activated carbon as a
      reductant and template.
AB  - A novel technique has been devised for the synthesis of microporous alpha
      Cr(2)O(3) (eskolaite). The technique was based on the formation of amorphous
      Cr(2)O(3) onto microporous activated carbon through adsorption-reduction of
      dichromate ions (Cr(2)O(7)(2-)) at the activated carbon/aqueous solution
      interface. Then, the Cr(2)O(3)-loaded carbon was thermally processed under
      oxidizing conditions to remove the carbon and recover the chromium oxide as alpha
      Cr(2)O(3). Both the Cr(2)O(3)-loaded carbon and the synthetic product were
      characterized by XRD, SEM, surface area and pore volume measurements. The
      synthetic eskolaite assayed 97.3% Cr(2)O(3) and its specific surface area was
      15.48 m(2)/g and pore size of 16.1 A.

PMID- 22365638
TI  - Reprint of "Update of the reference and HBM values derived by the German Human
      Biomonitoring Commission".
AB  - In 2007, we reviewed the working principles and working procedures of the German
      Human Biomonitoring Commission together with the reference values and human
      biomonitoring (HBM) values derived up to that time. Since then, the Commission
      has decided to derive additionally HBM I values on the basis of tolerable daily
      intakes and has used and evaluated this new approach on the metabolites of (2
      ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a
      HBM I value for thallium in urine, has recinded the HBM values for lead in blood,
      and has updated the HBM values for cadmium in urine. Based on the representative
      data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV),
      the Commission has updated the reference values for a large number of
      environmental pollutants in urine and blood of children in Germany. Since 2007,
      the Commission has derived new and updated reference values for PFOS and PFOA in
      human plasma, for thallium in urine, for aromatic amines in urine, for a
      comprehensive number of phthalate metabolites in urine, and for organochlorine
      pesticides in human breast milk. Furthermore, the Commission has evaluated
      background exposure levels for two naphthalene metabolites and acrylamide (using
      acrylamide-haemoglobin adduct) for the general population. This paper reports the
      new values, including those already published, in order to provide an updated
      overview.

PMID- 22365639
TI  - [Thyrotoxicosis and cerebral venous sinus thrombosis, causality or chance
      alone?].

PMID- 22365640
TI  - Modest improvement in 20 years of kidney cancer care in the Netherlands.
AB  - AIM: For an evaluation of the progress achieved in the field of kidney cancer
      care in the Netherlands in the last decades, we described trends in incidence,
      treatment, mortality and relative survival. METHODS: All adult patients newly
      diagnosed with kidney cancer between 1989 and 2009 (N=32,545) were selected from
      the Netherlands Cancer Registry. Age-standardised incidence and mortality rates
      were calculated. Follow-up was completed until January 2010. In order to assess
      trends estimated annual percentages of change (EAPC) were estimated. RESULTS: The
      incidence of kidney cancer has been fairly stable between 1989 and 2001 with a
      European Standardised Rate of approximately 11 per 100,000 person years (PY).
      Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%;
      95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly
      over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in
      treatment were observed, except for the introduction of targeted therapies for
      stage IV disease, since 2005. The 5-year relative survival improved from 51% in
      1989-1994 to 58% in 2005-2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in
      survival was especially seen in males, younger age groups and low stages.
      CONCLUSIONS: The incidence of kidney cancer has increased slightly, and survival
      improved modestly, resulting in a decreasing mortality. A positive effect of the
      introduction of targeted therapies for metastatic kidney cancer was observed in 1
      year relative survival. For progress in kidney cancer care, effective prevention
      strategies and new therapies remain warranted.

PMID- 22365641
TI  - Aerosols generated by hardcopy devices and other electrical appliances.
AB  - In recent years the pollution of indoor air with ultrafine particles has been an
      object of intensive research. Several studies have concurred in demonstrating
      that outdoor air makes only a limited contribution to polluting indoor air with
      ultrafine particles, provided significant sources in the immediate neighborhood
      are absent. Nowadays, electrical devices operated in homes and offices are
      identified as particle emission sources. A comparison of the emission rates can
      be made by calculating the total number of particles released with respect to the
      operating time. The identified particles are condensed semi-volatile organic
      compounds with a low percentage of non-volatile inorganic components. To
      characterize the indoor exposure to airborne particles, an algorithm has been
      developed which permits a realistic calculation of the particle intake and
      deposition in the human respiratory tract from measured size and time resolved
      particle number concentrations following the model of the International
      Commission on Radiological Protection.

PMID- 22365643
TI  - [Molecular biomarkers involved in the tumor dedifferentiation process of thyroid
      carcinoma of epithelial origin: perspectives].
AB  - Although papillary or follicular well-differentiated thyroid carcinoma usually
      has a good prognosis, a proportion of well-differentiated thyroid carcinomas show
      a more aggressive behavior with local recurrence and metastases, either at
      diagnosis (in less than 5% of cases) or over time. Although there are several
      scoring systems to assess prognosis of well-differentiated thyroid carcinoma,
      mainly based on clinical and pathological data, there is currently no valid
      criterion to define an adequate, differential treatment for patients with low
      risk carcinomas as compared to those with more aggressive tumors. Identification
      of patients with a high risk at the time of diagnosis would be essential to
      develop new therapeutic strategies and to improve follow-up, and molecular
      biomarkers could be a highly useful tool for this purpose.

PMID- 22365642
TI  - Interplay between gene expression noise and regulatory network architecture.
AB  - Complex regulatory networks orchestrate most cellular processes in biological
      systems. Genes in such networks are subject to expression noise, resulting in
      isogenic cell populations exhibiting cell-to-cell variation in protein levels.
      Increasing evidence suggests that cells have evolved regulatory strategies to
      limit, tolerate or amplify expression noise. In this context, fundamental
      questions arise: how can the architecture of gene regulatory networks generate,
      make use of or be constrained by expression noise? Here, we discuss the interplay
      between expression noise and gene regulatory network at different levels of
      organization, ranging from a single regulatory interaction to entire regulatory
      networks. We then consider how this interplay impacts a variety of phenomena,
      such as pathogenicity, disease, adaptation to changing environments, differential
      cell-fate outcome and incomplete or partial penetrance effects. Finally, we
      highlight recent technological developments that permit measurements at the
      single-cell level, and discuss directions for future research.

PMID- 22365644
TI  - A mixture model to correct misclassification of gestational age.
AB  - PURPOSE: Misclassification of gestational age based on the last menstrual period
      (LMP) in routinely collected data creates bias in newborn birthweight and
      gestational age-related indicators. Common correction methods have not been
      evaluated. We developed a normal mixture model for use with SAS software to
      correct misclassification of gestational age and compare its performance with
      other available correction methods and estimates of gestational age. METHODS:
      Using the 2007 United States natality file from the National Center for Health
      Statistics, we compared LMP preterm and postterm birth rates and gestational age
      specific birthweight percentiles against a reference subset of births, where the
      likelihood of misclassification in gestational age was minimized, before and
      after correction by a normal mixture model, two truncation methods, and the
      clinical/obstetric estimate of gestational age. RESULTS: The mixture model
      corrected preterm and postterm birth rates by 90% and 41% respectively, but
      previous methods performed poorly. The mixture model was also superior in
      correcting birthweight percentiles 50 and 90 with error reductions in the range
      of 68% to 85% between 28 and 36 weeks of gestation, where most misclassification
      occurred. CONCLUSIONS: The mixture model behaved consistently better than
      truncation methods, particularly between weeks 28 and 36 of gestation.

PMID- 22365646
TI  - Outcome of Chagas cardiomyopathy in comparison to ischemic cardiomyopathy.
AB  - BACKGROUND: Chagas cardiomyopathy and ischemic heart disease (IHD) are frequent
      causes of chronic systolic heart failure (CHF) in areas where the former is
      endemic. Nonetheless, a specific comparison of outcome and role of etiology of
      CHF failure has not been performed in patients with both conditions. METHODS: Two
      hundred twenty two patients with Chagas cardiomyopathy and 79 with IHD with CHF
      were included in the study. A Cox proportional hazards model was used to
      establish independent predictors of mortality for the studied population.
      Survival analysis was performed with the Kaplan-Meir product limit method.
      RESULTS: In the multivariable model, Beta-Blocker therapy [(hazard ratio
      (HR)=0.36; 95% confidence interval (CI) 0.24 to 0.52; p<0.005)], Chagas etiology
      of CHF (HR=3.6; 95% CI 2.0 to 6.5; p<0.005), serum sodium levels (HR=0.95; 95% CI
      0.91 to 0.98; p<0.005), digoxin use (HR=2.1; 95% CI 1.19 to 3.80, p=0.01), and
      spironolactone use (HR=1.7; 95% CI 1.10 to 2.80; p=0.02) were determined
      independent predictors of all-cause mortality for this cohort. Probability of
      survival at 12, 24, 36, 48, and 60 months was 92%, 92%, 88%, 81%, and 78%,
      respectively, in IHD patients, and 79%, 61%, 49%, 41%, and 35%, respectively, in
      Chagas cardiomyopathy patients (p<0.005). CONCLUSION: Outcome in patients with
      chronic systolic heart failure secondary to Chagas cardiomyopathy is poorer than
      that seen in those with IHD.

PMID- 22365645
TI  - Inverse associations between perceived racism and coronary artery calcification.
AB  - PURPOSE: To evaluate whether racial discrimination is associated with coronary
      artery calcification (CAC) in African-American participants of the Coronary
      Artery Risk Development in Young Adults (CARDIA) study. METHODS: The study
      included American Black men (n = 571) and women (n = 791) aged 33 to 45 years in
      the CARDIA study. Perceived racial discrimination was assessed based on the
      Experiences of Discrimination scale (range, 1-35). CAC was evaluated using
      computed tomography. Primary analyses assessed associations between perceived
      racial discrimination and presence of CAC using multivariable-adjusted logistic
      regression analysis, adjusted for age, gender, socioeconomic position (SEP),
      psychosocial variables, and coronary heart disease (CHD) risk factors. RESULTS:
      In age- and gender-adjusted logistic regression models, odds of CAC decreased as
      the perceived racial discrimination score increased (odds ratio [OR], 0.94; 95%
      confidence interval [CI], 0.90-0.98 per 1-unit increase in Experiences of
      Discrimination scale). The relationship did not markedly change after further
      adjustment for SEP, psychosocial variables, or CHD risk factors (OR, 0.93; 95%
      CI, 0.87-0.99). CONCLUSIONS: Perceived racial discrimination was negatively
      associated with CAC in this study. Estimation of more forms of racial
      discrimination as well as replication of analyses in other samples will help to
      confirm or refute these findings.

PMID- 22365647
TI  - Cardiovascular effects of B-vitamins and/or N-3 fatty acids: the SU.FOL.OM3
      trial.
AB  - BACKGROUND: Mechanisms involved in coronary stenosis evolution are different than
      those involved in clinical events. Because of differential vascular effects, N-3
      polyunsatured fatty acids (PUFA) and B vitamins could have differential effects
      on different types of cardiovascular clinical events in high-risk patients.
      METHODS: We analyzed the effects of n-3 PUFA and of B vitamins on both coronary
      revascularization and on hard coronary events risks in a subgroup of the
      SU.FOL.OM3 trial, a randomized, double-blind, placebo-controlled secondary
      prevention trial. Data were analyzed according to the intention-to-treat
      principle, with the use of Cox proportional-hazards models. RESULTS: After a mean
      follow-up of 4.2 +/- 1.0 years among the 1,863 participants with coronary heart
      disease, 163 coronary revascularizations were performed, and 95 patients
      experienced a hard coronary event. Neither treatment with n-3 PUFA, nor treatment
      with B vitamins was associated with any significant effect on the occurrence of
      hard coronary events. Allocation to n-3 PUFA was not associated with any
      significant effect on coronary revascularization. However, treatment with B
      vitamins was associated with a statistically significant 52% increase in the risk
      of coronary revascularization (multivariate HR: 1.52; 95% CI: [1.11-2.10];
      p=0.01). CONCLUSIONS: Neither n-3 PUFA, nor B vitamins reduced the rates of hard
      coronary events and of coronary revascularization. Furthermore, B vitamins
      significantly increased the rate of coronary revascularization. Consistent with
      the findings of previous trials, our results do not support the routine use of
      dietary supplements containing n-3 PUFA and argue against using dietary
      supplements containing B-vitamins in coronary patients in secondary
      cardiovascular prevention.

PMID- 22365648
TI  - The possible role of chemotherapy in antiangiogenic drug resistance.
AB  - The use of antiangiogenic drugs for cancer treatment was welcomed because of the
      hypothesis that they would be much less likely to lose their therapeutic activity
      as a result of tumor-acquired resistance over time. Unfortunately, the clinical
      experience has shown that acquired resistance to antiangiogenic therapeutic
      strategies is possible since many patients whose tumors initially respond to
      drugs such as bevacizumab (a monoclonal antibody against VEGF), sorafenib, or
      sunitinib (tyrosine kinase inhibitors targeting VEGF receptors and PDGF
      receptors) or metronomic chemotherapy (e.g. low dose cyclophosphamide) become
      nonresponsive, often within months of therapy initiation. Indeed, the role of
      associated antineoplastic chemotherapy in antiangiogenic resistance seems to be
      ignored by the previous studies and the real part played by these drugs has to be
      written yet. The studies undertaken on antiangiogenic resistance mainly involved
      mechanisms directly related to the antiangiogenic drugs alone and as such lead
      one to ask whether the acquired resistance to angiogenesis pathway-targeting
      might also be mediated by the chemotherapeutic drugs usually associated (at least
      into the clinic) with these types of drugs. The proposed hypothesis is concerning
      the possibility that the acquired resistance to antiangiogenic therapy could be
      actively and heavily modulated by the choice of the associated chemotherapeutic
      drug. The chemotherapeutic compounds may delay or accelerate the process through
      the induction, upregulation or downregulation of pro-angiogenic or anti
      angiogenic factors or their receptors in the tumor, endothelial and other type of
      cells of the tumor microenvironment. In conclusion, the consequences of our
      hypothesis could be promptly translated into the preclinical studies and verified
      in clinical trials, involving cancer patients resistant to chemotherapy plus
      antiangiogenic drug schedules.

PMID- 22365649
TI  - Myoelectric signals of levator palpebrae superioris as a trigger for FES to
      restore the paralyzed eyelid.
AB  - Some closed loop FES systems have been designed to restore the blinking function
      of facial paralysis patients. All of them used myoelectric signal of orbicularis
      oculi at the normal side as the trigger to stimulate the paralyzed side. They
      were limited to the one side facial paralysis. Here we proposed that the
      myoelectric signal of levator palpebrae superioris could be used as the trigger
      to stimulate the paralyzed orbicularis oculi. Because the levator palpebrae
      superioris and the innervating nerve are intact, the myoelectric signal of the
      paralyzed side still could be used as the trigger. It will be more acceptable for
      the patients and have the potential to resolve the bilateral facial paralysis.

PMID- 22365650
TI  - Inflammatory cytokines as an underlying mechanism of the comorbidity between
      bipolar disorder and migraine.
AB  - A bi-directional association between mood disorders and migraine has been
      consistently reported. Nevertheless, the neurobiological substrate underlying the
      association between these disorders remains unknown. In the article herein we
      review evidence for the role of inflammatory cytokines in the neurobiology of
      bipolar disorder and migraine. In addition, inflammation is hypothesized to be a
      shared pathophysiological mechanism subserving the bipolar disorder and migraine
      concomitance. A derivative of this hypothesis is that pharmacological treatments
      primarily targeting the inflammatory system may have symptom suppressing effects
      in bipolar disorder.

PMID- 22365651
TI  - Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and
      allostasis in epilepsy, depression, and post-traumatic stress disorder.
AB  - A theory is proposed to explain the benefits of yoga practices in diverse,
      frequently comorbid medical conditions based on the concept that yoga practices
      reduce allostatic load in stress response systems such that optimal homeostasis
      is restored. It is hypothesized that stress induces (1) imbalance of the
      autonomic nervous system (ANS) with decreased parasympathetic nervous system
      (PNS) and increased sympathetic nervous system (SNS) activity, (2) underactivity
      of the gamma amino-butyric acid (GABA) system, the primary inhibitory
      neurotransmitter system, and (3) increased allostatic load. It is further
      hypothesized that yoga-based practices (4) correct underactivity of the PNS and
      GABA systems in part through stimulation of the vagus nerves, the main peripheral
      pathway of the PNS, and (5) reduce allostatic load. Depression, epilepsy, post
      traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions
      that are exacerbated by stress, have low heart rate variability (HRV) and low
      GABAergic activity, respond to pharmacologic agents that increase activity of the
      GABA system, and show symptom improvement in response to yoga-based
      interventions. The observation that treatment resistant cases of epilepsy and
      depression respond to vagal nerve stimulation corroborates the need to correct
      PNS underactivity as part of a successful treatment plan in some cases. According
      to the proposed theory, the decreased PNS and GABAergic activity that underlies
      stress-related disorders can be corrected by yoga practices resulting in
      amelioration of disease symptoms. This has far-reaching implications for the
      integration of yoga-based practices in the treatment of a broad array of
      disorders exacerbated by stress.

PMID- 22365652
TI  - A novel 'microscopic method' of shrinkage calculation in the pursuance of
      shrinkage based histopathological guidelines for interpretation of surgical
      margins.

PMID- 22365653
TI  - ICON: food allergy.
AB  - Food allergies can result in life-threatening reactions and diminish quality of
      life. In the last several decades, the prevalence of food allergies has increased
      in several regions throughout the world. Although more than 170 foods have been
      identified as being potentially allergenic, a minority of these foods cause the
      majority of reactions, and common food allergens vary between geographic regions.
      Treatment of food allergy involves strict avoidance of the trigger food.
      Medications manage symptoms of disease, but currently, there is no cure for food
      allergy. In light of the increasing burden of allergic diseases, the American
      Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical
      Immunology; World Allergy Organization; and American College of Allergy, Asthma &
      Immunology have come together to increase the communication of information about
      allergies and asthma at a global level. Within the framework of this
      collaboration, termed the International Collaboration in Asthma, Allergy and
      Immunology, a series of consensus documents called International Consensus ON
      (ICON) are being developed to serve as an important resource and support
      physicians in managing different allergic diseases. An author group was formed to
      describe the natural history, prevalence, diagnosis, and treatment of food
      allergies in the context of the global community.

PMID- 22365654
TI  - Omalizumab and the risk of malignancy: results from a pooled analysis.
AB  - BACKGROUND: Since initial registration, the omalizumab clinical trial database
      has expanded considerably, with a doubling of patients exposed in the clinical
      trial environment. Previous pooled data (2003) from phase I to III studies of
      omalizumab showed a numeric imbalance in malignancies arising in omalizumab
      recipients (0.5%) compared with control subjects (0.2%). The previous analysis
      was based on limited available data, warranting further investigation. OBJECTIVE:
      We sought to examine the incidence of malignancy using comprehensive pooled data
      from clinical trials of omalizumab-treated patients. METHODS: This pooled
      analysis included data from 67 phase I to IV clinical trials. The prespecified
      primary analysis assessed the incidence of primary malignancy in 32 randomized,
      double-blind, placebo-controlled (RDBPC) trials. RESULTS: There were 11,459
      unique patients in all clinical trials (7,789 received omalizumab). The primary
      analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254
      omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence
      rates per 1,000 patient-years of observation time for omalizumab- and placebo
      treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94),
      respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary
      malignancies were of varying histologic type and occurred in a number of
      different organ systems; no cluster of histologies was identified. CONCLUSIONS:
      In this pooled analysis no association was observed between omalizumab treatment
      and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data
      suggest that a causal relationship between omalizumab therapy and malignancy is
      unlikely.

PMID- 22365655
TI  - Feline parathyroid hormone: validation of hormonal assays and dynamics of
      secretion.
AB  - Validated assays for quantification of intact parathyroid hormone (I-PTH) are no
      longer available. Moreover, the third-generation PTH assay that only detects the
      whole PTH molecule (W-PTH) has never been tested in cats. The work presented here
      is aimed to validate a commercially available assay for measurement of I-PTH and
      W-PTH in cats and to study the dynamics of PTH secretion in healthy cats. Our
      results show that both assays are reliable for the measurement of feline PTH. In
      healthy adult cats W-PTH concentration (15.1 +/- 1.6 pg/mL) was greater (P <
      0.001) than I-PTH concentration (9.1 +/- 0.7 pg/mL). The dynamics of PTH
      secretion in response to changes in extracellular calcium (Ca(2+)) were
      investigated in 13 cats by studying PTH-Ca(2+) curves. PTH-Ca(2+) curves were
      obtained by intravenous infusion of disodium ethylenediaminetetraacetic acid and
      CaCl(2). PTH was measured using both I-PTH and W-PTH assays. During hypocalcemia
      a sigmoidal curve that was similar when measured with I-PTH or W-PTH was
      obtained. The maximal PTH concentration in response to hypocalcemia was greater
      with W-PTH (179.6 +/- 41.9 pg/mL) than with I-PTH (67.6 +/- 10.5 pg/mL; P =
      0.01). However, hypercalcemia resulted in an equivalent PTH inhibition, with both
      assays yielding PTH concentrations as follows: W-PTH = 4.0 +/- 0.4 pg/mL and I
      PTH = 4.9 +/- 0.3 pg/mL (NS). Parameters of the feline PTH-Ca(2+) curve are
      similar to what has been previously reported in dogs.

PMID- 22365656
TI  - Apolipoprotein E genotype and the cardiovascular disease risk phenotype: impact
      of sex and adiposity (the FINGEN study).
AB  - Here the impact of APOE genotype on CHD risk in UK adults is reported, along with
      an analysis of APOE genotype * BMI/age/sex interactions. APOE genotype had a
      significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio,
      triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with
      an overall trend towards lower and higher risk in E2- and E4-carriers,
      respectively, relative to the wild-type E3/E3 genotype. A greater impact of
      genotype on TC:HDL-C was observed in females, which explained 16% of the
      variability in this outcome versus 6% in males. APOE genotype was also associated
      with plasma C-reactive protein and adhesion molecule concentrations (P<0.05),
      with significant genotype * BMI interactions observed. Our observations indicate
      that the association between the APOE genotype and CHD risk is unlikely to be
      homogenous and highlights the risk of inaccurate estimations of genotype
      phenotype associations in population subgroups without appropriate stratification
      for sex and adiposity.

PMID- 22365657
TI  - Controlling angiogenesis in breast cancer: a systematic review of anti-angiogenic
      trials.
AB  - PURPOSE: Angiogenesis is critical for tumor growth and a promising therapeutic
      target. This review will summarize and analyze data from clinical trials of anti
      angiogenic agents in the treatment of breast cancer (BC). DESIGN: A systematic
      search of PubMed and conference databases was performed to identify reports of
      randomized clinical trials investigating specific anti-angiogenic agents in the
      treatment of BC. RESULTS AND DISCUSSION: Phase III trials in advanced BC have
      demonstrated a reduction in the risk of disease progression (22-52%), improved
      response rates and net improvements in progression-free survival of 1.2 to 5.5
      months, but no significant improvements in overall survival with the addition of
      bevacizumab to chemotherapy. Results of phase III trials in early breast cancer
      have been inconsistent. Bevacizumab-containing regimens have also been associated
      with higher overall adverse event rates compared to chemotherapy alone. Phase III
      trials of the tyrosine kinase inhibitor sunitinib were negative, while randomized
      phase II trials of sorafenib and pazopanib have improved some outcomes when
      combined with chemotherapy or targeted therapy compared to controls. In addition
      to expected vascular class safety signals, tyrosine kinase inhibitors show "off
      target" side effects. Ongoing clinical trials evaluating combinatorial strategies
      based on biological synergies and translational studies identifying biological
      predictors of response will be crucial to establish meaningful clinical benefits
      in selected BC populations. CONCLUSION: Most trials of anti-angiogenic agents in
      BC have reported improved response rate and progression-free survival but no
      increase in overall survival compared to chemotherapy alone. Optimizing the
      therapeutic indices of these agents is a focus of ongoing research and will be
      critical to their future development.

PMID- 22365658
TI  - Inhibitors of apoptosis proteins and IL-1beta: a tangled relationship.
AB  - Inhibitors of apoptosis proteins (IAPs) are important regulators of both cell
      death and inflammation. In this issue of Immunity, Vince et al. (2012) report
      that inhibition of IAPs results in the processing and secretion of IL-1beta
      through RIP3-mediated caspase-1- and caspase-8-dependent pathways.

PMID- 22365659
TI  - JAK's SOCS: a mechanism of inhibition.
AB  - SOCS1 and SOCS3 are specific inhibitors for JAK tyrosine kinases. In this issue
      of Immunity, Babon et al. (2012) discovered the inhibition mechanism of SOCS3 by
      employing nuclear magnetic resonance and classical enzyme kinetics.

PMID- 22365660
TI  - Toll-like receptor 9, what o'clock is it?
AB  - In this issue of Immunity, Silver et al. (2012) provide evidence that murine Toll
      like receptor 9 (TLR9) expression and function in innate and adaptive immunity is
      controlled by the circadian cycle.

PMID- 22365661
TI  - Regulatory T cells stay on course.
AB  - Regulatory T (Treg) cells are thought to be susceptible to conversion into
      effector T cells. In this issue of Immunity, Miyao et al. (2012) provide evidence
      that the apparent plasticity of murine Foxp3(+) Treg cells is largely restricted
      to a defined subset of poorly committed Foxp3(+) cells.

PMID- 22365662
TI  - Losing TREC with age.
AB  - In this issue of Immunity, den Braber et al. (2012) highlight differences in
      naive T cell lifespan between mice and humans. Their data suggest that mechanisms
      of naive T cell maintenance may differ between mice and men.

PMID- 22365663
TI  - Constitutive type I interferon modulates homeostatic balance through tonic
      signaling.
AB  - Interferons (IFNs) were discovered as cytokines induced during and protecting
      from viral infection. They have been documented to play essential roles in
      numerous physiological processes beyond antiviral and antimicrobial defense,
      including immunomodulation, cell cycle regulation, cell survival, and cell
      differentiation. Recent data have also uncovered a potentially darker side to
      IFN, including roles in inflammatory diseases, such as autoimmunity and diabetes.
      IFN can have effects in the absence of acute infection, highlighting a
      physiologic role for constitutive IFN. Type I IFNs are constitutively produced at
      vanishingly low quantities and yet exert profound effects, mediated in part
      through modulation of signaling intermediates required for responses to diverse
      cytokines. We review evidence for a yin-yang of IFN function through its role in
      modulating crosstalk between multiple cytokines by both feedforward and feedback
      regulation of common signaling intermediates and postulate a homeostatic role for
      IFN through tonic signaling in the absence of acute infection.

PMID- 22365664
TI  - The 3' enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral
      immunity in follicular helper T cells.
AB  - A main role for interleukin-4 (IL-4) is in humoral immunity, and follicular
      helper CD4(+) T (Tfh) cells may be an intrinsic IL-4 source. Here we demonstrate
      that conserved noncoding sequence 2 (CNS2) is an essential enhancer element for
      IL-4 expression in Tfh cells but not in Th2 cells. Mice with a CNS2 deletion had
      a reduction in IgG1 and IgE production and in IL-4 expression in Tfh cells.
      Tracking of CNS2 activity via a GFP reporter mouse demonstrated that CNS2-active
      cells expressed several markers of Tfh cells: CXCR5, PD-1, and ICOS; the
      transcriptional master regulator Bcl6; and the cytokines IL-21 and IL-4. These
      CNS2-active cells were mainly localized in B cell follicles and germinal centers.
      The GFP(+) Tfh cells were derived from GFP(-) naive T cells after in vivo
      systemic immunization. These results indicate that CNS2 is an essential enhancer
      element required for IL-4 expression in Tfh cells controlling humoral immunity.

PMID- 22365665
TI  - Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1
      activation.
AB  - Interleukin-1beta (IL-1beta) is a potent inflammatory cytokine that is usually
      cleaved and activated by inflammasome-associated caspase-1. To determine whether
      IL-1beta activation is regulated by inhibitor of apoptosis (IAP) proteins, we
      treated macrophages with an IAP-antagonist "Smac mimetic" compound or genetically
      deleted the genes that encode the three IAP family members cIAP1, cIAP2, and
      XIAP. After Toll-like receptor priming, IAP inhibition triggered cleavage of IL
      1beta that was mediated not only by the NLRP3-caspase-1 inflammasome, but also by
      caspase-8 in a caspase-1-independent manner. In the absence of IAPs, rapid and
      full generation of active IL-1beta by the NLRP3-caspase-1 inflammasome, or by
      caspase-8, required the kinase RIP3 and reactive oxygen species production. These
      results demonstrate that activation of the cell death-inducing ripoptosome
      platform and RIP3 can generate bioactive IL-1beta and implicate them as
      additional targets for the treatment of pathological IL-1-driven inflammatory
      responses.

PMID- 22365666
TI  - Maintenance of peripheral naive T cells is sustained by thymus output in mice but
      not humans.
AB  - Parallels between T cell kinetics in mice and men have fueled the idea that a
      young mouse is a good model system for a young human, and an old mouse, for an
      elderly human. By combining in vivo kinetic labeling using deuterated water,
      thymectomy experiments, analysis of T cell receptor excision circles and CD31
      expression, and mathematical modeling, we have quantified the contribution of
      thymus output and peripheral naive T cell division to the maintenance of T cells
      in mice and men. Aging affected naive T cell maintenance fundamentally
      differently in mice and men. Whereas the naive T cell pool in mice was almost
      exclusively sustained by thymus output throughout their lifetime, the maintenance
      of the adult human naive T cell pool occurred almost exclusively through
      peripheral T cell division. These findings put constraints on the extrapolation
      of insights into T cell dynamics from mouse to man and vice versa.

PMID- 22365668
TI  - Preparation of single donor platelet with low antibody titers for all patients.
AB  - Platelet concentrates from ABO-identical donors are the components of choice for
      patients. However, since inventories are generally insufficient and because there
      is usually a relative abundance of group O donors, perfect matches are not always
      possible. It is therefore the accepted practice for platelets to be transfused
      out of the ABO group when ABO-identical platelets are unavailable.
      Notwithstanding, the transfusion of platelets containing high titers of
      antibodies to the antigens on the red blood cells of the patient can cause
      clinically significant hemolysis. The way to improve the safety of group O
      platelets has focused on defining a safe level of antibodies or reducing the
      volume of incompatible plasma. In the current study, 107 group O single donor
      platelets (SDP) were modified after collecting the platelet pellet in a bag. The
      AB plasma was added instead of the donor's own plasma. The direct agglutination
      titers of anti-A/anti-B in the original group O SDPs' plasma were performed by
      doing a gel test, resulting in from 1:4 to 1:1024. The prevalence of high titers
      (i.e., at least 1:64 in our study) was relatively high, ~63% for anti-A and 78%
      for anti-B. The titer of residual anti-A/anti-B in the modified SDPs ranged from
      negative to 1:8. In most of the modified SDPs anti-A/anti-B could not be detected
      in the plasma (58.9% and 52.3%, respectively). The results indicate that our
      modified SDPs have very low titers; that is, acting as a universal SDP which is
      safe for all ABO patients. This modified SDP form is a more convenient way to
      overcome the risk from incompatible plasma or loss of platelets during the
      process of volume reduction and can help effectively manage our inventory.

PMID- 22365670
TI  - Pseudoaneurysm of the cystic artery as a complication of laparoscopic
      cholecystectomy.

PMID- 22365669
TI  - Asthma control assessed in the EGEA epidemiological survey and health-related
      quality of life.
AB  - BACKGROUND: The aims were to assess 1) the relationship of asthma control
      assessed by combining epidemiological survey questions and lung function to
      Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled
      asthma reach similar generic HRQL levels as individuals without asthma. METHODS:
      The analysis included 584 individuals without asthma and 498 with asthma who
      participated in the follow-up of the Epidemiological study on Genetics and
      Environment of Asthma (EGEA). Asthma control was assessed from survey questions
      and lung function, closely adapted from the 2006-2009 Global Initiative for
      Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1
      7) and the generic SF-36 (scores range: 0-100) were used. RESULTS: Adjusted mean
      total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9
      and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p
      < 0.0001). The differences in SF-36 scores between individuals with controlled
      asthma and those without asthma were minor and not significant for the PCS (-1, p
      = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8
      domains (<5.1) although statistically significant for 4 domains. CONCLUSION:
      These results support the discriminative properties of the proposed asthma
      control grading system and its use in epidemiology.

PMID- 22365667
TI  - Reward-related learning via multiple memory systems.
AB  - The application of a neuroeconomic approach to the study of reward-related
      processes has provided significant insights in our understanding of human
      learning and decision making. Much of this research has focused primarily on the
      contributions of the corticostriatal circuitry, involved in trial-and-error
      reward learning. As a result, less consideration has been allotted to the
      potential influence of different neural mechanisms such as the hippocampus or to
      more common ways in human society in which information is acquired and utilized
      to reach a decision, such as through explicit instruction rather than trial-and
      error learning. This review examines the individual contributions of multiple
      learning and memory neural systems and their interactions during human decision
      making in both normal and neuropsychiatric populations. Specifically, the
      anatomical and functional connectivity across multiple memory systems are
      highlighted to suggest that probing the role of the hippocampus and its
      interactions with the corticostriatal circuitry via the application of model
      based neuroeconomic approaches may provide novel insights into neuropsychiatric
      populations that suffer from damage to one of these structures and as a
      consequence have deficits in learning, memory, or decision making.

PMID- 22365671
TI  - A SAS macro for direct adjusted survival curves based on Aalen's additive model.
AB  - Aalen's additive model defines the covariate effects on the survival outcome to
      be time-varying. The aim of this paper is to explore the application of Aalen's
      model in assessing treatment effects, adjusting for possibly different patient
      profiles between the treatment groups. We treat Aalen's model as the underlying
      model and compute the direct adjusted survival curves for different treatments.
      The treatment comparison can be performed by finding a confidence interval for
      the difference between two direct adjusted survivals. We developed a SAS macro
      that calculates the direct adjusted survival estimates and the standard errors,
      based on Aalen's model. In this paper, we give two examples to explain the syntax
      for using the macro.

PMID- 22365672
TI  - Infrared spectroscopy: a potential tool in huanglongbing and citrus variegated
      chlorosis diagnosis.
AB  - Huanglongbing (HLB) and citrus variegated chlorosis (CVC) are serious threats to
      citrus production and have caused considerable economic losses worldwide,
      especially in Brazil, which is one of the biggest citrus producers in the world.
      Neither disease has a cure nor an efficient means of control. They are also
      generally confused with each other in the field since they share similar initial
      symptoms, e.g., yellowing blotchy leaves. The most efficient tool for detecting
      these diseases is by polymerase chain reaction (PCR). However, PCR is expensive,
      is not high throughput, and is subject to cross reaction and contamination. In
      this report, a diagnostic method is proposed for detecting HLB and CVC diseases
      in leaves of sweet orange trees using attenuated total reflectance Fourier
      transform infrared spectroscopy and the induced classifier via partial least
      squares regression. Four different leaf types were considered: healthy, CVC
      symptomatic, HLB-symptomatic, and HLB-asymptomatic. The results show a success
      rate of 93.8% in correctly identifying these different leaf types. In order to
      understand which compounds are responsible for the spectral differences between
      the leaf types, samples of carbohydrates starch, sucrose, and glucose, flavonoids
      hesperidin and naringin, and coumarin umbelliferone were also analyzed. The
      concentration of these compounds in leaves may vary due to biotic stresses.

PMID- 22365673
TI  - Monoliths with proteins as chiral selectors for enantiomer separation.
AB  - Recent advances in monolithic systems, especially the development of
      functionalized monoliths, make it more tentative for separation science, such as
      enantiomer separation. Proteins, as one category of well-acknowledged chiral
      selectors, have won a reputation of separating a wide range of enantiomeric
      mixtures due to varieties of functional groups at their surface. However, the
      combination of protein and monoliths for chiral analysis is seldom reported, thus
      the state-of-the-art in monolith with proteins as chiral selectors for enantiomer
      separations is comprehensively reviewed. This review focuses on organic polymer
      monoliths, silica monoliths and molecularly imprinted polymer monoliths
      functionalized by proteins or glycoproteins, introducing the possible mechanisms,
      the immobilizing ways as well as the associated problems. Related areas such as
      partial filling technique are also covered.

PMID- 22365674
TI  - Thiophene anchored coumarin derivative as a turn-on fluorescent probe for Cr3+:
      cell imaging and speciation studies.
AB  - A thiophene-coumarin hybrid molecule, (6E)-6-((thiophen-2-yl)methyleneamino)-2H
      chromen-2-one (TMC) has been prepared and its single crystal X-ray structure is
      reported. TMC can selectively detect Cr(3+) in presence of other common cations.
      Both TMC and its Cr(3+) complex are well characterized by different spectroscopic
      techniques like (1)H NMR, QTOF-MS ES(+), FTIR and elemental analysis as well. TMC
      exhibits fluorescence enhancement upon binding Cr(3+) in CH(3)CN-HEPES buffer
      (0.02 M, pH 7.4) (4:6, v/v) medium. Detection limit of the method is 1 * 10(-6)M.
      Binding constant is estimated with the Benesi-Hildebrand method and the value 8 *
      10(4) indicates a fairly strong interaction between TMC and Cr(3+). Speciation
      studies have been performed in a fast and environment friendly way using least
      sample volume, less hazardous chemicals and solvents. Cr(3+) assisted restricted
      rotation around the imine bond and inhibited photo-induced electron transfer from
      the N,S-donor sites to the coumarin unit are responsible for fluorescence
      enhancement. TMC is capable to detect intracellular Cr(3+) in living cells.

PMID- 22365675
TI  - New tetradecyltrimethylammonium-selective electrodes: surface composition and
      topography as correlated with electrode's life span.
AB  - Two conventional plastic membrane electrodes that are selective for the
      tetradecyltrimethylammonium cation (TTA) have been prepared. The ion exchangers
      of these sensors were the ion associate, TTA-PT, and the ion aggregate, TTA-PSS,
      where PT and PSS are phosphotungstate and polystyrene sulfonate, respectively.
      The following performance characteristics of the TTA-PT- and TTA-PSS-containing
      electrodes were found: conditioning time of 30 and 20 min; potential response of
      58.2 and 61.1 mV/TTA concentration decade; rectilinear concentration ranges of
      2.0 * 10(-5)-5.0 * 10(-2) and 1.5 * 10(-5)-7.9 * 10(-2) mol L(-1); average
      working pH ranges of 4.0-10.5 and 3.8-10.7; life spans of 20 and 28 weeks, and
      isothermal temperature coefficients of 4.44 * 10(-4) and 6.10 * 10(-4)V/ degrees
      C, respectively. Both electrodes exhibited high selectivity for TTA with an
      increasing number of inorganic and quaternary ammonium surfactant cations. These
      electrodes have been successfully applied to assay an antiseptic formulation
      containing TTA. Surface analyses using electron microscopy and X-ray
      photoelectron spectroscopy were used to determine the cause of the limited life
      span of plastic membrane electrodes.

PMID- 22365676
TI  - Comprehensive analysis of gluten in processed foods using a new extraction method
      and a competitive ELISA based on the R5 antibody.
AB  - The only treatment for coeliac disease is to follow a strict, life-long gluten
      free diet. It is therefore essential to use a highly sensitive, specific
      technique for gluten analysis in foods. Nowadays, the usual method for
      determining gluten content in gluten-free foods, internationally accepted by the
      Codex Alimentarius Commission, is the R5 antibody-based sandwich ELISA, combined
      with the cocktail-extraction solution. This technique requires at least two
      epitopes in the protein, but in hydrolysed foods, proteins are fragmented during
      food processing and converted into peptides in which only one toxic epitope may
      appear. Consequently, it was necessary to develop a new competitive immunoassay
      that, together with a reliable, compatible extraction solution, would provide a
      complete gluten analysis in any kind of food. We analysed commercial foods and
      home-made maize breads spiked with a known amount of gliadins using the sandwich
      R5 ELISA and the new competitive R5 ELISA that has been developed. These foods
      had previously been extracted with 60% ethanol/water, the cocktail solution or
      the new extracting solution called UPEX (universal prolamin and glutelin
      extractant solution). The complementary SDS-PAGE and western blot techniques were
      also used to confirm the gluten content. The limits of detection and
      quantification of the competitive R5 ELISA were 0.36 and 1.22 ng/ml of gliadins,
      respectively. The intra- and inter-assay precisions based on two samples were,
      respectively, 7.3% and 5.4% for the first sample and 9.9% and 6.3% for the
      second. This new assay was a better technique than the sandwich R5 ELISA for
      detecting gliadins quantitatively in hydrolysed foods. Regarding the extraction
      procedure, we did not find any significant interference from components of the
      UPEX solution at the concentration used. In addition, the UPEX solution
      extraction was compatible with the R5 western blot and mass spectrometry
      techniques. The competitive R5 ELISA we developed, combined with the UPEX
      solution described here, is a very useful tool for detecting and quantifying
      gluten in any kind of food samples, including heat-treated and/or hydrolysed
      ones.

PMID- 22365677
TI  - A disposable chitosan-modified carbon fiber electrode for dengue virus envelope
      protein detection.
AB  - A chitosan-modified carbon fiber electrode (CFE) for dengue virus envelope
      protein (DENV) was developed. Antibodies against DENV were covalently immobilized
      on the chitosan (CHIT) matrix after activation with sodium periodate. Cyclic
      voltammetries and scanning electron microscopies analysis were performed to
      monitor steps involved in the CFE surface modification. Amperometric response of
      the competitive immunoassays was generated by hydrogen peroxide reaction with the
      peroxidase conjugated to DENV and 2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic
      acid) (ABTS) as mediator. The immunosensor showed a lower limit of detection for
      DENV (0.94 ng mL(-1)) than previously described and a linear range from 1.0 to
      175 ng mL(-1), in concentration levels clinically relevant for dengue virus
      diagnosis. The intra- and inter-assay were respectively 5.8% and 3.6%. The unique
      and simple design of this immunoassay format provides an economical alternative
      for the manufacture of other sensitive sensors.

PMID- 22365678
TI  - Gas diffusion flow injection determination of thiomersal in vaccines.
AB  - A new simple gas diffusion flow injection method has been developed for the
      determination of thiomersal in biological samples. The method is based on cold
      vapor generation of monoatomic mercury from thiomersal reaction with acidic
      stannous chloride solution (0.6%) acting as reducing agent. The evolved mercury
      partially diffuses through a Teflon membrane into an acidic permanganate (2.25 *
      10(-4) mol L(-1)) acceptor stream, where it is oxidized and re-converted to
      Hg(II). The resulting decrease in acceptor stream absorbance is sensitively
      monitored at 528 nm. Flow injection variable parameters such as reagents
      concentrations, injected volume, reactor length, temperature and flow rate were
      carefully investigated and optimized. The concentration-response relationship was
      linear over a concentration range of 1-30 mg L(-1) with a correlation coefficient
      greater than 0.99 and a good reproducibility (RSD<1.42%, n=6) at 10 mg L(-1). A
      detection limit of 0.07 mg L(-1) (S/N=3) and a sampling frequency of 5 samples h(
      1) were obtained. The method was successfully applied for the determination of
      thiomersal in different types of vaccines and gave results in close agreement
      with those found by previously established HPLC method with no significant
      interference from vaccines matrices.

PMID- 22365679
TI  - Modification of VTMS hybrid monolith via thiol-ene click chemistry for capillary
      electrochromatography.
AB  - An n-octadecanethiol (C(18))/3-mercapto-1-propane-sulfonate (MPS) modified
      organic-inorganic hybrid silica monolithic column possessing vinyl ligands
      through thiol-ene click chemistry for capillary electrochromatography (CEC) is
      described. The proposed column is prepared via the sol-gel process by in situ co
      condensation using vinyltrimethoxysilane (VTMS) and tetra-methoxysilane (TMOS) as
      precursors. Examination by SEM shows that the capillary has homogenous
      macroporous morphology and is well attached to the inner wall of the capillary.
      The obtained C(18)-MPS-VTMS silica hybrid monolithic column demonstrated an
      enhanced hydrophilic property and could be applied as a reversed-phase stationary
      phase in CEC directly. Compared with unmodified VTMS silica hybrid monolithic
      column, stronger EOF was observed using this monolithic column. VTMS/TOMS ratios
      in the reaction mixture were varied and 1:3 was found to be optimum. Good
      separations of benzenes, aromatic amines, acids and peptides were achieved, the
      lowest plate height of ~ 3MUm was obtained, the peak symmetry range from 0.98 to
      1.29. The resulting C(18)-MPS-VTMS silica hybrid monolithic column can be used in
      different separation modes, including reversed phase mode and ion exchange mode.

PMID- 22365680
TI  - Reduction of acid effects on trace element determination in food samples by CH4
      mixed plasma-DRC-MS.
AB  - A robust method for trace element determination in food samples by addition of
      methane to the plasma of a dynamic reaction cell mass spectrometer (CH(4) mixed
      plasma-DRC-MS) was developed. Addition of 3 mL min(-1) methane to Ar-plasma
      eliminates the signal suppressions of various elements (As, Se, Hg, etc.) due to
      the high concentration of nitric acid (10%, v/v). The CH(4)-Ar mixed plasma may
      compensate for the plasma cooling effects due to the highly concentrated nitric
      acid. The interfering polyatomic ions (40)Ar(12)C(+), (40)Ar(35)Cl(+) and
      (40)Ar(40)Ar(+) on (52)Cr(+), (75)As(+) and (80)Se(+) determination were removed
      effectively using the DRC with CH(4) as the reaction gas. The limits of
      quantification (LOQ, 10sigma) were 0.35 ng g(-1), 0.07 ng g(-1), 0.35 ng g(-1),
      0.07 ng g(-1), 0.15 ng g(-1), and 0.07 ng g(-1) for As, Cd, Cr, Hg, Pb and Se,
      respectively. The proposed method was applied to the determination of these trace
      elements in four food standard reference materials (NIST1577b, GBW10018,
      NIST1570a and GBW10016), and the results were in good agreement with the
      certified values.

PMID- 22365681
TI  - An optical sensor for mercuric ion based on immobilization of Rhodamine B
      derivative in PVC membrane.
AB  - A novel prepared mercuric ion PVC membrane sensor based on a Rhodamine B
      derivative (RND) as a selective sensing material was described. The sensor
      exhibited a specific fluorescent off-on response to Hg(2+), and showed a linear
      response over the Hg(2+) concentration range from 1.0 * 10(-9) to 2.0 * 10(-3)M
      with a very low detection limit of 8.1 * 10(-10)M in bulk method. The sensor has
      also been incorporated into a flow-cell for determination of Hg(2+) in flowing
      streams with improved sensitivity and detection limit. The sensor shows excellent
      selectivity toward Hg(2+) with respect to common coexisting cations. The proposed
      fluorescence optode was successfully applied to detect Hg(2+) in environmental
      water samples and fish.

PMID- 22365682
TI  - Direct matrix assisted laser desorption ionization mass spectrometry-based
      analysis of wine as a powerful tool for classification purposes.
AB  - The variables affecting the direct matrix assisted laser desorption ionization
      mass spectrometry-based analysis of wine for classification purposes have been
      studied. The type of matrix, the number of bottles of wine, the number of
      technical replicates and the number of spots used for the sample analysis have
      been carefully assessed to obtain the best classification possible. Ten different
      algorithms have been assessed as classification tools using the experimental data
      collected after the analysis of fourteen types of wine. The best matrix was found
      to be alpha-Cyano with a sample to matrix ratio of 1:0.75. To correctly classify
      the wines, profiling a minimum of five bottles per type of wine is suggested,
      with a minimum of three MALDI spot replicates for each bottle. The best algorithm
      to classify the wines was found to be Bayes Net.

PMID- 22365683
TI  - Simple and rapid determination of norethindrone in human plasma by supported
      liquid extraction and ultra performance liquid chromatography with tandem mass
      spectrometry.
AB  - We report for the first time an ultra performance liquid chromatographic method
      with tandem mass spectrometric detection (UPLC/MS/MS) for the determination of
      norethindrone alone in human plasma over the concentration range of 50.0-25000 pg
      mL(-1) using a sample volume of 0.250 mL. Norethindrone and its internal standard
      (ISTD), norethindrone-(13)C(2), were extracted from human plasma by supported
      liquid extraction (SLE). After evaporation of the organic solvent, samples were
      reconstituted and analyzed on an UPLC/MS/MS system. The UPLC system used a Waters
      BEH C18 (100 mm * 2.1mm, 1.7 MUm) column with mobile phase A of 0.05% formic acid
      in water:acetonitrile (65:35, v/v) and mobile phase B of 0.05% formic acid in
      methanol:acetonitrile (50:50, v/v). The flow rate was 0.500 mL min(-1). The
      method was fully validated. The inter-run accuracy and precision at the lower
      limit of quantitation (LLOQ), low, mid and high quality control (QC)
      concentration levels were 99.2-108.4% with a <8.1% CV (coefficient of variation),
      respectively. The validated method has been successfully applied to analysis of
      thousands of pharmacokinetic samples.

PMID- 22365684
TI  - Determination of puerarin in pharmaceutical and biological samples by capillary
      zone electrophoresis with UV detection.
AB  - A rapid and efficient capillary zone electrophoresis (CZE) method with
      ultraviolet detection has been successfully developed for the determination of
      puerarin in Xinkeshu capsules and biological samples. The optimal CZE conditions
      were determined to be 70 mM H(3)BO(3)-Na(2)B(4)O(7), pH 9.2, injection time 5s,
      applied voltage 25 kV, working temperature 25 degrees C and detection wavelength
      254 nm. Under these conditions, a linear range from 17.3 to 138 MUg/mL with the
      correlation coefficient of 0.9998 and limit of detection of 34.6 ng/mL (S/N=3)
      for puerarin were obtained. The relative standard deviation of the migration time
      and peak area of puerarin were 0.23-0.91, 0.43-1.62, 0.10-0.64 and 0.64-1.32% for
      intra-day and inter-day analyses, respectively. Satisfactory results were
      obtained for recovery and repeatability. The proposed method was successfully
      applied to analyze the puerarin content in Xinkeshu capsules and some biological
      samples with good results. It is suitable for applications in pharmaceutical
      industries for quality control and in clinical laboratories for therapeutic drug
      monitoring purposes.

PMID- 22365685
TI  - Fabrication of new single-walled carbon nanotubes microelectrode for
      electrochemical sensors application.
AB  - In this paper, we describe two simple different ways to fabricate an array of
      single-walled carbon nanotubes (SWCNT) microelectrodes from SWCNT network, grown
      on Si substrate, through micro-fabrication process. Two kinds of material,
      photoresist - organic compound and sputtered SiO(2), were used as an insulator
      layer for these arrays of SWCNT microelectrodes. The SWCNT microelectrodes were
      characterized by scanning electron microscopy (SEM), Raman spectroscopy, and
      electrochemical measurements. The SWCNT microelectrodes with sputtered SiO(2) as
      an insulator exhibit some prior advances to these used photoresist layer as
      insulator such as much stable in harsh condition (high active organic solvents)
      and high current density (24.94 MUA mm(-2) compared to 2.69 MUA mm(-2),
      respectively). In addition, the well-defined geometry of SWCNT microelectrodes is
      not only useful for investigating kinetics of electron transfer, but also
      promising candidate in electrochemical sensors application.

PMID- 22365686
TI  - Electrochemical immunosensor for carcinoembryonic antigen based on nanosilver
      coated magnetic beads and gold-graphene nanolabels.
AB  - A novel redox-active magnetic nanostructure was synthesized by using a wet
      chemical method for high-efficiency electrochemical immunoassay of
      carcinoembryonic antigen (CEA, as a model analyte). The nanostructures based on
      the combination of a magnetic nanocore, a layer of electroactive poly(o
      phenylenediamine) (PPD), and a silver metallic shell displayed good adsorption
      properties for the attachment of anti-CEA antibody selective to CEA. The magnetic
      nanostructure presented good redox behaviors to facilitate and modulate the way
      it was integrated into a magnetic carbon paste electrode. The assay was based on
      a sandwich-type immunoassay protocol by using nanogold-patterned graphene oxide
      nanoscales (AuNP-GO), conjugated with horseradish peroxidase-labeled anti-CEA, as
      secondary antibodies and biofunctionalized magnetic nanostructures as
      immunosensing probes. Under optimal conditions, the nanoparticle-based
      immunocomposites exhibited good electrochemical responses for the determination
      of CEA, and allowed the detection of CEA at a concentration as low as 1.0 pg mL(
      1) at a signal-to-noise ratio of 3. In addition, the magnetic immunosensing had
      good reproducibility, and acceptable accuracy, and could be successfully applied
      for the detection of CEA in the clinical serum specimens. Significantly, by
      controlling the target biomolecules, this assay can be easily extended for use
      with other immunosensings, and thus represents a versatile design routine.

PMID- 22365687
TI  - Gold nanoparticle extraction followed by o-phthaldialdehyde derivatization for
      fluorescence sensing of different forms of homocysteine in plasma.
AB  - This study reports a selective and sensitive method for fluorescent detection of
      total, protein-bound, free, and free oxidized homocysteine (HCys) using tris(2
      carboxyethyl)phosphine (TCEP) as a reducing agent, fluorosurfactant-capped gold
      nanoparticles (FSN-AuNP) as a preconcentrating probe, and o-phthaldialdehyde
      (OPA) as a derivatizing agent. TCEP was used to reduce the disulfide bonds of
      protein-bound and free oxidized HCys. FSN-AuNPs can extract HCys from a
      complicated complex because the FSN capping layer stabilizes the AuNPs in a high
      salt solution and inhibits non-specific adsorption. HCys was selectively
      derivatized with OPA in the absence of a nucleophile. By taking advantage of
      these features, the selectivity of the proposed system is greater than 100-fold
      for HCys and homocystine (HCys-HCys disulfide; diHCys) compared to any
      aminothiols. The limits of detection for HCys and diHCys were 4.4 and 4.6 nM,
      respectively. Different forms of plasma HCys were determined by varying the order
      of disulfide reduction with TCEP.

PMID- 22365688
TI  - Carbon nanotubes-ionic liquid nanocomposites sensing platform for NADH oxidation
      and oxygen, glucose detection in blood.
AB  - An excellent electrochemical sensing platform has been designed by combining the
      huge specific surface area of carbon nanotubes (CNTs) and the remarkable
      conductivity of ionic liquid (IL). IL can easily untangle CNTs bundles and
      disperse CNTs by itself under grinding condition due to the pi-pi interaction
      between CNTs and IL. The resulting nanocomposites showed an augmentation on the
      voltammetric and amperometric behaviors of electrocatalytic activity toward O(2)
      and NADH. Therefore, such an efficient platform was developed to fabricate
      mediator-free oxygen sensor and glucose biosensor based on glucose dehydrogenase
      (GDH). O(2) could be determined in the range of zero to one hundred percent of
      O(2) content with the detection limit of 126 MUg L(-1) (S/N=3). The glucose
      biosensor which was constructed by entrapping GDH into chitosan on the
      nanocomposites modified glassy carbon electrode surface, exhibited good
      electrocatalytic oxidation toward glucose with a detection limit of 9 MUM in the
      linear range of 0.02-1mM. We also applied the as-prepared sensors to detect
      oxygen and glucose in real blood samples and acquired satisfied results.

PMID- 22365689
TI  - Synthesis and time-gated fluorometric application of a europium(III) complex with
      a borono-substituted terpyridine polyacid ligand.
AB  - A new europium(III) complex with a borono-substituted terpyridine polyacid
      ligand, (4'-borono-2,2':6',2"-terpyridine-6,6"-diyl) bis(methylenenitrilo)
      tetrakis(acetate)-Eu(3+) (BTTA-Eu(3+)), has been designed and synthesized as a
      luminescence probe for hydrogen peroxide (H(2)O(2)). The complex is highly
      luminescent in aqueous buffers to display a typical Eu(3+) emission pattern with
      a sharp emission peak at 610 nm and a long luminescence lifetime of 1.34 ms. Upon
      reaction with H(2)O(2), the deboronation derivative of BTTA-Eu(3+), (4'-hydroxy
      2,2':6',2"-terpyridine-6,6"-diyl) bis(methylenenitrilo) tetrakis(acetate)-Eu(3+)
      (HTTA-Eu(3+)), can be generated. It was found that the luminescence of BTTA
      Eu(3+) was pH-insensitive, whereas that of HTTA-Eu(3+) was pH-dependent and could
      be remarkably weakened in neutral and basic buffers, which allowed BTTA-Eu(3+) to
      be a luminescence probe for the time-gated luminescence detection of H(2)O(2) in
      neutral and basic buffers. The H(2)O(2)-BTTA-Eu(3+) system was applied to monitor
      the kinetics of the palladium-catalyzed Suzuki cross-coupling reaction between
      BTTA-Eu(3+) and bromobenzene, which suggested a useful strategy for the
      application of time-gated luminescence technique in catalysis reaction
      researches.

PMID- 22365690
TI  - iTRAQ plus 18O: a new technique for target glycoprotein analysis.
AB  - A novel strategy combining iTRAQ with (18)O stable isotope labeling (iTRAQ plus
      (18)O) was established to identify N-glycosylation site, quantify the
      glycopeptides and non-glycosylated peptides, and obtain N-glycosylation site
      ratio on the target glycoprotein. In this approach, all peptides of four
      biological samples are labeled with four iTRAQ reagents in parallel, followed by
      PNGase F catalyzed labeling of N-glycosylation sites with H(2)(16)O and
      H(2)(18)O. Two sample groups are labeled with H(2)(16)O and the other two are
      labeled with H(2)(18)O. After the modification of MS precursor ion isolation
      window, tagged peptides are identified by LC-MS/MS, both glycopeptides and non
      glycopeptides are quantified simultaneously using ProteinPilotTM Software. With
      four samples to be maximally analyzed in parallel, this workflow supports
      accurate identification and quantification of glycopeptides in a site-specific
      fashion. Furthermore, N-glycosylation site ratios on serum haptoglobin (Hp) beta
      chain in healthy individuals as well as patients with hepatitis B virus (HBV),
      liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were quantified to
      validate the novel 'iTRAQ plus (18)O' method. Glycosite ratios of
      VVLHPN#YSQVDIGLIK were observed to change significantly in HCC patients compared
      with LC and HBV patients. This novel approach supports the screening of the
      target glycoproteins as biomarkers in clinical application.

PMID- 22365691
TI  - Determination of ultra-trace formaldehyde in air using ammonium sulfate as
      derivatization reagent and capillary electrophoresis coupled with on-line
      electrochemiluminescence detection.
AB  - The reaction between formaldehyde and ammonium ion to produce
      hexamethylenetetramine is well known. The reaction conditions are very easily
      controlled in situ and the experiment operation is very simple. However, such
      derivatization reaction for trace formaldehyde determination using capillary
      electrophoresis (CE) electrochemiluminescence (ECL) has not been reported before.
      In this study, the application of ammoniun sulfate as derivatization reagent to
      in-situ determination of formaldehyde in air was reported. Based on ECL
      enhancement of tris(2,2'-bipyridyl)ruthenium(II) with hexamethylenetetramine, a
      novel approach for the determination of ultra-trace formaldehyde in air using CE
      coupled with on-line ECL of tris(2,2'-bipyridyl)ruthenium(II) has been developed.
      The parameters affecting separation and detection such as detection potential,
      concentration and pH of phosphate buffer, and electrokinetic voltage, were
      investigated. Under the optimal conditions, the linear concentration range of
      formaldehyde in air was from 0.48 MUg/m(3) to 96 mg/m(3) (linear range covering 5
      orders of magnitude). The limit of detection (3sigma) was 0.15 MUg/m(3). The
      relative standard deviations of peak height and migration time for six
      consecutive injection of 1 ng/mL formaldehyde derivative were 0.9% and 0.8%,
      respectively. The recoveries of formaldehyde in air were between 99.3% and 101%.

PMID- 22365692
TI  - Carbohydrate-functionalized surfactant vesicles for controlling the density of
      glycan arrays.
AB  - We report on the development of a method for rapidly characterizing the glycan
      binding properties of lectins. Catanionic surfactant vesicles, prepared from
      cationic and anionic surfactants, spontaneously formed in water and remained
      stable at room temperature for months. By varying the amount of glycoconjugate
      added during preparation, glycans were incorporated onto the outer surface of the
      vesicles in a controlled range of densities. The carbohydrate-functionalized
      vesicles were applied to commercially available, nitrocellulose-coated slides to
      generate glycan arrays. As proof of concept, the binding of two lectins,
      concanavalin A and peanut agglutinin, to the arrays was quantified using a biotin
      avidin fluorescence sandwich assay. This facile method of preparing a glycan
      array by using vesicles to control the glycan density can be expanded to provide
      a platform for characterizing unknown lectins.

PMID- 22365693
TI  - Utilization of endogenous fatty acid stores for energy production in bovine
      preimplantation embryos.
AB  - Although current embryo culture media are based on carbohydrate metabolism of
      embryos, little is known about metabolism of endogenous lipids. L-carnitine is a
      beta-oxidation cofactor absent in most culture media. The objective was to
      investigate the influence of L-carnitine supplementation on bovine embryo
      development. Abattoir-derived bovine cumulus oocyte complexes were cultured and
      fertilized. Post-fertilization, presumptive zygotes were transferred into a basic
      cleavage medium +/- carbohydrates (glucose, lactate and pyruvate) +/- 5 mm L
      carnitine and cultured for 4 days in vitro. In the absence of carbohydrates
      during culture, embryos arrested at the 2- and 4-cell stages. Remarkably, +L
      carnitine increased development to the morula stage compared to +carbohydrates
      alone (P < 0.001). The beneficial effects of L-carnitine were further
      demonstrated by inclusion of carbohydrates, with 14-fold more embryos reaching
      the morula stage after culture in the +carbohydrates +L-carnitine group compared
      to the +carbohydrates group (P < 0.05). Whereas there was a trend for +L
      carnitine to increase ATP (P = 0.09), ADP levels were higher and ATP: ADP ratio
      were 1.9-fold lower (main effect, P < 0.05) compared to embryos cultured in -L
      carnitine. Therefore, we inferred that +L-carnitine embryos were more
      metabolically active, with higher rates of ATP-ADP conversion. In conclusion, L
      carnitine supplementation supported precompaction embryo development and there
      was an additive effect of +L-carnitine +carbohydrates on early embryo
      development, most likely through increased beta-oxidation within embryos.

PMID- 22365694
TI  - Morphometrically-distinct sperm subpopulations defined by a multistep statistical
      procedure in ram ejaculates: intra- and interindividual variation.
AB  - The existence of sperm subpopulations within the mammalian ejaculate has now been
      widely recognized. However, to the best of our knowledge, no data exist regarding
      the existence of sperm morphometric subpopulations within the ovine ejaculate.
      Computer assisted sperm morphometry analysis (ASMA) data and clustering methods
      were used in this study to identify sperm-head subpopulations in ram semen. Two
      experiments were carried out. In Experiment 1, ejaculates from 226 mature rams of
      the Manchega breed belonging to 36 different herds were used. A minimum of 100
      sperm heads were analyzed from each male and eight morphometric characteristics
      for each individual sperm were recorded. Subpopulation analysis was performed in
      sequential steps: variable group analysis and correlation analysis to select
      which morphometric characteristics to use in cluster analyses; nonhierarchical
      clustering analysis using sperm head length and p2a (also known as roundness)
      shape factor as initial classificatory variables; and hierarchical clustering
      analysis to obtain the final number of clusters. The clustering analyses, based
      on 26,306 individual cells, revealed the existence of four sperm subpopulations
      (SP1, SP2, SP3 and SP4) with different morphometric characteristics. Significant
      differences in the proportion of spermatozoa in the SP1 and SP3 were found
      between rams belonging to different herds. In Experiment 2, the intra- and
      intermale variability on the distribution of sperm subpopulations was assessed.
      Three ejaculates from each of 21 rams were collected and the same multistep
      clustering analysis was performed. For all subpopulations defined, the intermale
      variability resulted in high values, being the intramale variability much lower.
      This fact would allow the use of sperm head morphometry to characterize a male
      and might provide valuable information to asses its fertility. In conclusion, our
      results show that using computer assisted sperm morphometry analysis and
      multivariate cluster analyses, four sperm subpopulations with different head
      phenotype were identified in ram ejaculates.

PMID- 22365695
TI  - Flow cytometry as an estimation tool for honey bee sperm viability.
AB  - Flow cytometry is a method to conduct a multiparameter analysis of cells
      suspended in liquid and passing through a laser beam. Analyses of human and other
      mammal sperm using this method have already been performed but its application
      for insect semen is still the subject of investigation. Semen isolated from honey
      bee Apis mellifera seminal vesicles was dyed using SYBR-14 and propidium iodide
      (PI). The fluorescence of the SYBR-14 stained cells was analyzed in a green
      fluorescence channel (FL-1), while the PI fluorescence was analyzed in a red
      fluorescence channel (FL-3). Living and dead cell populations were separated
      using a density dot plot and the percentage of each in the sample was calculated.
      Flow cytometry seems to be an effective tool for assessing the viability of honey
      bee semen, solving the problems of distinguishing and counting the double-stained
      cells.

PMID- 22365696
TI  - Progesterone exposure of the preovulatory follicle in the seasonally anestrous
      ewe alters the expression of angiogenic growth factors in the early corpus
      luteum.
AB  - Gonadotrophin releasing hormone (GnRH)-induced ovulation in seasonally anestrous
      ewes is associated with a high incidence of defective corpora lutea (CL), which
      can be completely eliminated by priming ewes with progesterone before GnRH
      treatment, but the physiological basis of this has remained elusive. This study
      tested the hypothesis that progesterone priming eliminates defective luteal
      function by altering the expression of Vascular Endothelial Growth Factor (VEGF),
      its receptor VEGFR-2, and angiopoietin (ANG)-1, ANG-2 and their receptor TIE-2 in
      the early CL. Fifteen seasonally anestrous ewes were treated by i.m. injection
      with 20 mg of progesterone 3 days before the start of GnRH treatment, while
      another 15 animals served as controls. Intravenous injections of 500 ng GnRH were
      given to all the ewes every 2 h for 28 h, followed by a 300 MUg GnRH bolus
      injection to synchronize the preovulatory luteinizing hormone (LH) surge. Corpora
      lutea were collected 1, 2 and 4 days after ovulation and analyzed for protein and
      mRNA expression of VEGF, VEGFR-2, ANG-1, ANG-2 and Tie-2 using Western
      Immunoblotting and in situ hybridization. VEGF, VEGFR-2 and ANG-1 expression was
      significantly higher (P <= 0.05) in the CL of progesterone-primed animals
      compared to non-primed ones. However, no differences were observed in the ANG-2
      or Tie-2 expression levels between the two treatment groups. These data suggest
      that progesterone priming of the preovulatory follicle alters the expression of
      some angiogenic growth factors in the early CL, leading to greater vascular
      stability and thereby normal luteal function.

PMID- 22365697
TI  - Ovarian hydrobursitis in female camels (Camelus dromedarius): the role of
      Chlamydophila abortus and a trial for medical treatment.
AB  - The occurrence of Chlamydophila abortus in female camels affected with ovarian
      hydrobursitis and a trial for medical treatment were studied. A total of 111
      cases were included in two experiments. In Experiment 1, sera from 51 affected
      cases were tested for C. abortus antibody using enzyme-linked immunosorbent assay
      (ELISA). In Experiment 2, 60 female camels affected with bilateral ovarian
      hydrobursitis were divided into treated and control groups (n = 30 each). Based
      on the bursal diameter, females of both groups were subdivided into those having
      small (< 5 cm), medium (5-7 cm) or large (> 7 cm) bursae. Treated group received
      20 mg/kg body weight oxytetracycline intramuscular, 4% lotagen intrauterine, and
      500 MUg cloprostenol intramuscular. Controls did not receive any treatment. All
      females were observed for 90 days non-return rate (NRR) and calving rate (CR).
      Antibodies against C. abortus were observed in 44/51 (86.3%) of the affected
      females. The 90 days NRR of the treated and control groups were 13/30 (43.3%) and
      0/30 (0.0%), respectively, (P = 0.001), while the CR were 10/30 (33.3%) and 0/30
      (0.0%), respectively, (P = 0.01). Based on bursal size, the 90 days NRR were
      11/15 (73.3%), 2/7 (28.6%) and 0/8 (0.0%) for treated females having small,
      medium and large bursa, while the CR were 9/15 (60%), 1/7 (14.3%), and 0/8
      (0.0%), respectively, (P = 0.01). In conclusion, it seems that C. abortus may be
      responsible for the spreading of the ovarian hydrobursitis syndrome in
      dromedaries. Small sized bursa could be medically treated.

PMID- 22365698
TI  - Effect of GnRHa, pimozide and Ovaprim on ovulation and plasma sex steroid
      hormones in African catfish Clarias gariepinus.
AB  - Nine groups each of four fish were injected with a single intramuscular dose of
      the following preparations: Physiological saline (0.9% NaCl) as a control group,
      0.5 ml kg(-1) Ovaprim, 20 and 40 MUg kg(-1) BW of GnRHa, 8 and 16 mL kg(-1)
      pimozide tablets and the following combination of GnRHa with pimozide (GP): 20
      MUg + 4 mg, 30 MUg + 8 mg and 40 MUg + 16 mg kg(-1) BW. The primary oocyte
      diameter (POD) before hormone administration ranged from 943.3 to 1071.0 MUm. The
      latency periods (LP) were in the range of 9.0 to 12.0 h after injection. The
      highest ovulation ratio (OR) was observed in groups Ovaprim, GP(30 + 8) and GP(40
      + 16). Other treatments were effective for ovulation, the ovulation ratio in
      Groups G(40) and GP(20 + 4) were significantly higher than G(20) treatment. The
      ovulation index (OI) was in the range 62 to 77% and showed significant
      differences among groups. There was no significant difference in fertilization
      ratio (FR) among Ovaprim, GP(30 + 8) and GP(40 + 16) groups, while there were
      significant difference between the previous group and G(20) and G(40) groups.
      Control, P8, P16 showed negative results in all the parameters LP, OED, OR, OI
      and FR. Levels of sex steroids were analyzed on 6 and 12 h after initiation of
      treatments. A significant increase in plasma E(2) with GP(30 + 8) injection was
      observed 6 and 12 h after injection, while there were no significant increase
      between all the other groups 6 h after injection. Treatments with GP(20 + 4)
      resulted in a significant increase in plasma T concentration in females compared
      with control after 6 h. In contrast, plasma T and E(2) concentrations were lower
      during the combined GP(20 + 4), GP(30 + 8) and GP(40 + 16) after 12 h than after
      16 h of injection. The combined treatments (GnRHa + PIM) are better compared with
      Ovaprim which gave the same results, they have some advantages, such as reliable
      response and low cost. Ovaprim is more than 3 to 5-fold of the cost of (GnRH +
      PIM). Therefore, this method could be useful tool for commercial catfish breeders
      to ensure spawning success.

PMID- 22365699
TI  - Characterization of the estrous cycle and reproductive traits of the aoudad
      (Ammotragus lervia) in captivity.
AB  - In this study the estrous cycle of the aoudad has been analyzed and characterized
      for the first time, using non-invasive methods for tracking reproductive
      cyclicity. The duration of the estrous cycle is 23 days (range 16-32 days), with
      a luteal phase of 17 days (range 12-27 days) and an interluteal phase of 6 days
      (range 3-14 days). The estrous cycle did not differ between females, but it was
      affected by the time of the year. Intraindividual variation of the cycle was
      observed in one out of the nine individuals. The average hormone concentration
      values, the estrogen:progestogen ratio, as well as their minimum and maximum
      values for each interluteal and luteal phases of the estrous cycle, are shown.
      Interindividual differences found in these values were basically associated with
      age. Females tended to start their cycle when in the presence of an adult male.
      Anestrus was observed in study females except for the oldest (14 years old). Age
      and anestrus onset were correlated, with younger females starting earlier than
      the older ones. This study reveals that Ammotragus reproductive biology is more
      similar to that of Capra than Ovis, except for some endocrinological features.

PMID- 22365700
TI  - Canine perinatal mortality: a cohort study of 224 breeds.
AB  - Canine perinatal mortality is known to be relatively high. However, the
      literature on perinatal mortality in dogs is still sparse and often refers to a
      single or only a few breeds. The aim of this large-scale observational study was
      to describe the perinatal mortality in purebred dogs of various breeds at both
      puppy and litter level. In addition, the influence of breed, breed size, litter
      size, age of the bitch, litter number and season for whelping on the risk of
      perinatal mortality at litter level was studied and the mean litter size at eight
      days and eight wks after birth was calculated. A retrospective cohort study was
      performed by studying 10,810 litters of 224 breeds registered in the Norwegian
      Kennel Club in 2006 and 2007. Perinatal mortality was defined as the sum of
      stillborn puppies and puppies that died during the first wk after birth (early
      neonatal mortality) and was present in 24.6% of the litters. Eight percent of the
      puppies died before eight days after birth, with 4.3% as stillbirth and 3.7% as
      early neonatal mortality. For most breeds the perinatal mortality was low, but
      for some breeds a higher perinatal mortality was found. The mean litter size at
      eight days and eight wks after birth was 4.97 (+/-0.02) and 4.92 (+/-0.02)
      puppies, respectively. Of all puppies born, only 1% died during the period from
      eight days to eight wks after birth. Random effects logistic regression analysis
      indicated that increasing litter size and age of the bitch were associated with
      an increased risk of stillbirth, early neonatal mortality and total perinatal
      mortality at the litter level (P < 0.001). The random breed effect was
      significant for all outcomes. Litter number also had a significant effect on
      stillbirth, early neonatal mortality and total perinatal mortality at the litter
      level, with the highest risk of perinatal mortality found in the first litter (P
      < 0.001). Further, the risk of early neonatal mortality was doubled in litters
      with stillborn puppies. No significant effect of whelping season on perinatal
      mortality at litter level was found. An interaction existed between the age of
      the bitch and litter number and the risk of stillbirth was three times as high
      (odds ratio = 3.00) in litters from bitches having their first litter after the
      age of six y. Breed was a more important determinant of perinatal mortality in
      litters than breed size. However, more than 90% of the variation in perinatal
      mortality was found at the individual litter level and efforts to minimize puppy
      mortality should be targeted at the management of the individual litter rather
      than at the breed level.

PMID- 22365701
TI  - Angiotensin II, progesterone, and prostaglandins are sequential steps in the
      pathway to bovine oocyte nuclear maturation.
AB  - Oocyte meiotic resumption is triggered by the ovulatory gonadotropin surge; in
      cattle, angiotensin II (AngII) and prostaglandins (PG) are key mediators of this
      gonadotropin-induced event. Here, we tested the hypothesis that progesterone
      (P(4)) is also involved in oocyte meiotic resumption induced by the gonadotropin
      surge. In Experiment I, P(4) induced nuclear maturation in a dose-dependent
      manner using a coculture of follicular hemisections and cumulus-oocyte complexes.
      In the second experiment, using an in vivo model, an injection of mifepristone
      (MIFE; P(4) receptor antagonist) at the antrum of preovulatory follicles
      prevented GnRH-induced oocyte meiotic resumption in vivo. In Experiment III
      (coculture system similar to that of Experiment I), MIFE prevented stimulatory
      effects of AngII on resumption of meiosis, but saralasin (AngII receptor
      antagonist) did not inhibit P(4) actions. In Experiments IV and V, fibroblast
      growth Factor 10 (FGF10; known to suppress steroidogenesis in granulosa cells),
      blocked AngII-but not P(4)-induced oocyte meiotic resumption. Therefore, we
      inferred that AngII is upstream to P(4) in a cascade to induce meiotic
      resumption. Previously, we had reported that AngII acted throughout the PGs
      pathway to modulate nuclear progression. In Experiment V, indomethacin inhibited
      resumption of meiosis induced by P(4), providing further support to the AngII
      P(4) sequential effect on meiotic resumption. In conclusion, we inferred that
      AngII, P(4) and PGs are sequential steps in the same pathway that culminates with
      bovine oocyte maturation.

PMID- 22365702
TI  - Preimplantation antagonism of adrenomedullin action compromises fetoplacental
      development and reduces litter size.
AB  - Concentrations of adrenomedullin (ADM) in circulation, the uterus, and corpora
      lutea (CL) increase during pregnancy. We previously reported a temporal-spatial
      pattern of ADM level and gene expression of Adm and its receptor components, from
      early pregnancy through midpregnancy to late pregnancy in rats. Two earlier
      reports using an in vivo model of ADM antagonism demonstrated the important roles
      of ADM in the post-implantation period. Treatment with ADM receptor blocker
      hADM22-52 starting from gestation Day 8 or Day 14 resulted in fetal-placental
      growth restriction and reduction in litter size. In this study, the endogenous
      ADM actions were abolished in the preimplantation period by infusing the
      antagonist for the ADM receptor (hADM22-52) with the osmotic (Alzet) pump from
      Days 1-4 of pregnancy. We inferred that ADM, acting through the ADM receptor, had
      critical roles during preimplantation, as brief inhibition of ADM action by
      hADM22-52 during this period reduced litter size by restricting placental growth
      and increasing fetal resorption in midpregnancy.

PMID- 22365703
TI  - Corpus luteum development and function and relationship to pregnancy during the
      breeding season in the Mediterranean buffalo.
AB  - The aim of this study was to ascertain corpus luteum (CL) development and
      function in buffaloes synchronized and mated by artificial insemination (AI)
      during the breeding season. Italian Mediterranean buffalo cows (n = 43) at 86.5
      +/- 2.7 days postpartum were synchronized by the Ovsynch-TAI Program and
      inseminated using frozen thawed semen at 20 and 44 h after the second injection
      of GnRH. The CL dimensions (diameter and area) and blood flow were examined on
      Days 5, 10, 15, 20, and 25 after AI by realtime B-mode/colour-Doppler
      ultrasonography. The resistive index (RI), pulsatility index (PI) and time
      average medium velocity (TAMV) were recorded at each time, together with CL
      dimensions. Blood samples were taken on the days of ultrasonography for
      progesterone (P4) assay by RIA. Data were grouped into pregnant or non-pregnant
      and retrospectively analyzed by repeated measure ANOVA and correlation analyses.
      Dimensions of the CL on Days 10, 20, and 25 after AI were greater (P < 0.01) in
      buffaloes pregnant on Day 45 (n = 18) compared with non-pregnant buffaloes (n =
      25). The former buffaloes also showed a greater (P < 0.01) rate of CL growth
      between Days 5 and 10 after AI. Blood flow to the CL on Day 10 after AI showed a
      higher TAMV (P < 0.01) and lower RI (P < 0.05) in pregnant buffaloes compared
      with non-pregnant buffaloes. Negative correlations were observed on Day 10 after
      AI between CL diameter and RI (r = -0.61; P < 0.01) and PI (r = -0.60; P < 0.01);
      P4 concentrations and RI (r = -0.46; P < 0.02); and RI and pregnancy (r = 0.45; P
      < 0.02). Positive correlations were observed between pregnancy and CL size (r =
      0.54; P < 0.01), DeltaCL diameter between Days 5 and 10 (r = 0.52; P < 0.01),
      DeltaCL area between Days 5 and 10 (r = 0.48; P < 0.015), and DeltaP4 between
      Days 5 and 10 (r = 0.50; P < 0.01). Based on these findings it is concluded that
      the period between Day 5 and 10 is very important for CL growth and crucial in
      evaluating pregnancy. Accordingly, the assessment of CL parameters during the
      period from Day 5 to Day 10 after AI might be used to predict the likelihood of
      an ongoing pregnancy.

PMID- 22365704
TI  - Cellular and molecular characterization of the impact of laboratory setup on
      bovine in vitro embryo production.
AB  - One of the main objectives related to performing comparative analysis of
      embryonic transcriptomes is to share information with other reproductive
      biologists or commercial service providers. Biological extracts influence
      performance of in vitro production systems and affect the reproducibility of
      results between production sites; these sources of variation could impede the
      potential for knowledge transfer. The objective of the present study was to
      assess the impact of the production site when sharing a common in vitro embryo
      production protocol. Biological extracts and semen were shared between production
      sites and thus removed as potential sources of variation. To remove the impact of
      blastocyst staging, all comparisons used expanded blastocysts. Although
      blastocyst yields and the number of Tunel positive cells per embryo differed
      between production sites, blastocysts were morphologically very similar in
      regards to cell number, their allocation to either the trophoblast or inner cell
      mass, or their gender ratio. These observations were also confirmed at the gene
      expression level, as indicated by highly similar transcript abundances. Only 36
      genes out of the 16,121 expressed during bovine prehatching development were
      statistically differentially expressed, of which a large proportion were
      associated with the apoptotic process. These results highlighted the impact of
      laboratory set up, including personnel experience, when replicating an in vitro
      production system. Although inherent differences may arise, given the similarity
      of results between production sites, we concluded that embryo production
      protocols have the potential to be transferred and shared.

PMID- 22365705
TI  - GnRH dose reduction decreases pituitary LH release and ovulatory response but
      does not affect corpus luteum (CL) development and function in llamas.
AB  - Gonadotrophin releasing hormone (GnRH) is commonly used in llamas to induce
      ovulation; however, the consequence of reduced doses of GnRH on luteinizing
      hormone (LH) release, ovulatory response, and subsequent corpus luteum (CL)
      development and function have apparently not been investigated. Hence, we
      examined the effect of gradual reduction of gonadorelin acetate (GnRH) dosage on
      pituitary LH release, ovulatory response, CL development, and plasma progesterone
      concentrations in llamas. Non-pregnant, non-lactating adult llamas were examined
      once daily by transrectal ultrasonography, and those with a follicle >=8 mm in
      diameter that had grown for three consecutive days were randomly assigned to
      receive 50 (GnRH50, n = 23), 25 (GnRH25, n = 29), 12.5 (GnRH12.5, n = 29), or
      6.25 MUg (GnRH6.25, n = 29) of GnRH, or 0.5 mL of PBS (Control group, n = 16) im.
      In a subset (7 or 8 animals/group), intense blood sampling was done to measure LH
      concentrations. All females were examined by ultrasonography every 12 h from
      treatment (Day 0) to Day 2 to determinate ovulation, and thereafter on alternate
      days until Day 16 to evaluate CL development (9-13 animals/group). Also, blood
      samples for progesterone determination were taken (9 or 10 animals/group) on
      alternate days from Days 0-16. Ovulatory response (%) was highest (P < 0.05) in
      the GnRH50 (82.6), intermediate in the GnRH25 (72.3) and GnRH12.5 (75.9) groups,
      and lowest in the GnRH6.25 group (48.3). No ovulations were detected in the
      Control group. Mean peak LH concentrations (ng/mL) were highest (P < 0.05) for
      GnRH50 (6.2), intermediate for GnRH25 (4.4) and GnRH12.5 (2.9), and lowest for
      GnRH6.25 (2.2) groups. In addition, based on regression analysis, llamas with an
      LH peak <4 ng/mL were less likely to ovulate. Llamas given 50 MUg of GnRH
      released more (P < 0.05) pituitary LH and had an LH surge of longer duration than
      those given 25, 12.5, or 6.25 MUg. However, in those that ovulated, neither GnRH
      treatment nor treatment by time interaction affected (P > 0.05) CL diameter or
      plasma progesterone concentrations. In summary, reducing the dose of GnRH
      gradually decreased the magnitude of the preovulatory LH surge and ovulatory
      response; however, subsequent CL development and plasma progesterone
      concentrations were not affected.

PMID- 22365706
TI  - "To wheeze or not to wheeze": that is not the question--the sequel.

PMID- 22365707
TI  - Can simple echocardiographic measures reduce the number of cardiac magnetic
      resonance imaging studies to diagnose right ventricular enlargement in congenital
      heart disease?
AB  - BACKGROUND: Right ventricular (RV) enlargement is used as a criterion for the
      treatment of RV outflow tract dysfunction in patients with congenital heart
      disease. Although RV volumes are most accurately measured by cardiac magnetic
      resonance (CMR), CMR is a limited resource. The aim of this study was to
      investigate whether simple echocardiographic measurements can adequately predict
      RV volumes below clinical thresholds, thereby reducing the need for CMR in some
      patients. METHODS: Children with repaired tetralogy of Fallot, double-outlet
      right ventricle, or truncus arteriosus who underwent CMR and echocardiography
      within a 4-week interval were retrospectively studied. From the four-chamber
      view, indexed RV lateral wall length, indexed RV end-diastolic perimeter length,
      and indexed RV end-diastolic area (RVEDAi), were measured. Results were compared
      with CMR indexed RV volume. The sensitivity and specifity of echocardiographic
      threshold values predicting RV volumes < 170 mL/m(2) were determined. RESULTS:
      Fifty-one children (mean age, 12.7 +/- 3.5 years; 25 male, 26 female) were
      reviewed. RVEDAi was correlated with CMR indexed RV volume (r = 0.60, P < .0001).
      Indexed RV end-diastolic perimeter length and indexed RV lateral wall length were
      not correlated with CMR. RVEDAi < 20 cm(2)/m(2) had 100% specificity to predict
      indexed RV volume <= 170 mL/m(2) (area under the curve, 0.79), reducing the need
      for CMR in 15 of 51 patients (29%). A threshold RVEDAi of 22 cm(2)/m(2) would
      reduce the need for CMR in 21 of 51 patients (41%) at the expense of one false
      negative result. The coefficients of variation were 14.7% for intraobserver
      variability and 9.6% for interobserver variability. CONCLUSIONS: The specificity
      of echocardiography-measured RVEDAi can be set to predict RV volumes below a 170
      mL/m(2) threshold in 100% of cases. This may reduce the need for CMR to determine
      RV volumes in >=25% of patients with congenital heart disease, potentially
      reducing patient burden and costs.

PMID- 22365708
TI  - The dominant vein in the infraclavicular fossa is the axillary vein, not the
      subclavian.

PMID- 22365709
TI  - The effect of Definity on systemic and pulmonary hemodynamics in patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the pulmonary and systemic
      hemodynamic effects of Definity in patients with normal as well as those with
      elevated pulmonary artery pressure at baseline. Secondary objectives of the study
      were to evaluate safety and determine whether any potential immunologic reactions
      develop after Definity administration. METHODS: Patients with normal and elevated
      pulmonary artery systolic pressure undergoing right-heart catheterization
      received Definity (10 MUL/kg) as a slow bolus over 30 to 60 sec. Multiple
      sequential measurements of right atrial pressure, pulmonary artery systolic
      pressure, pulmonary artery diastolic pressure, mean pulmonary artery pressure,
      cardiac output, and pulmonary capillary wedge pressure were made before and after
      Definity administration. Vital signs, electrocardiograms, and blood samples were
      taken at multiple time points. Patients were followed for the development of
      adverse events. RESULTS: A total of 32 patients (16 with elevated pulmonary
      artery systolic pressure > 35 mm Hg) were enrolled. No significant changes in any
      pulmonary or systemic hemodynamic parameters, vital sign values,
      electrocardiographic data, or laboratory variables were found for data obtained
      before versus after receipt of Definity. CONCLUSIONS: The administration of
      Definity at the approved dosage does not change pulmonary or systemic
      hemodynamics in control patients or those with mild to moderate pulmonary
      hypertension. No significant changes were noted in a wide array of clinical and
      laboratory safety assessments after patients were exposed to Definity.

PMID- 22365710
TI  - Assessment of moyamoya disease using multidetector row computed tomography.
AB  - The recent introduction of multidetector row computed tomography (MDCT) scanners
      has enabled high-resolution 3-dimensional reconstruction. The purpose of this
      study was to establish a method to evaluate moyamoya disease using computed
      tomography angiography (CTA), specifically MDCT. Twenty-four patients (48 sides
      total) with moyamoya disease diagnosed by magnetic resonance angiography (MRA)
      were evaluated by means of CTA using MDCT by 3 independent observers, and the
      resulting 144 sides were analyzed. CTA and MRA were compared in terms of the
      steno-occlusive changes exhibited in each vessel. CTA and MRA scores were
      assigned on the basis of the severity of occlusive changes in the internal
      carotid artery, middle cerebral artery, anterior cerebral artery, and posterior
      cerebral artery. CTA scores were significantly correlated with MRA scores (P <
      .0001), and the 2 scores were in complete agreement in 57 sides (39.6%). The mean
      CTA score was significantly lower than the mean MRA score (P < .0001). Compared
      with CTA, MRA overestimated occlusion in 115 of the 576 vessels assessed. The
      mean MRA score was significantly higher in the overestimation group than in the
      good correlation group (P < .0001). CTA had a significantly higher rate of
      detection of moyamoya-affected vessels (P = .0001). Our data indicate that CTA
      using MDCT is a more reliable technique than MRA for diagnosing moyamoya disease.
      The ability to perform CTA quickly is a significant benefit for patients with
      moyamoya disease, particularly in pediatric and emergency cases.

PMID- 22365711
TI  - Using routine data for quality assessment in NeuroNet telestroke care.
AB  - BACKGROUND: Systematic clinical trials are often unavailable to evaluate and
      optimize operational telestroke networks. In a complementary approach, readily
      available routine clinical data were analyzed in this study to evaluate the
      effect of a telestroke network over a 4-year period. METHODS: Routine clinical
      data from the HELIOS hospital information system were compared before and after
      implementation of the NeuroNet concept, including neurologic acute stroke
      teleconsultations, standard operating procedures, and peer review quality
      management in 3 hospital cohorts: 5 comprehensive stroke centers, 5 NeuroNet
      hospitals, and 5 matched control hospitals. RESULTS: During the study period, the
      rate of thrombolytic therapy increased by 4.8% in NeuroNet hospitals, while
      ischemic stroke in-hospital mortality decreased (relative risk reduction ~29% in
      NeuroNet and control hospitals). The odds ratio for thrombolytic therapy in
      comprehensive stroke centers compared to NeuroNet hospitals was reduced from 3.7
      to 1.3 between 2006 and 2009. Comprehensive stroke care coding according to
      German Diagnosis Related Groups definitions increased by 45% in NeuroNet (P <
      .0001) and by 18% in control hospitals. CONCLUSIONS: Routine clinical data on in
      hospital mortality, the rate of thrombolytic therapy, and comprehensive stroke
      care coding reflect different aspects of acute stroke care improvement related to
      the implementation of the telemedical NeuroNet concept and unified quality
      management (standard operating procedure teaching concept, peer review process).
      Similar evaluation processes could contribute to quality monitoring in other
      telestroke networks.

PMID- 22365712
TI  - Surface markers for locating the pulleys and flexor tendon anatomy in the palm
      and fingers with reference to minimally invasive incisions.
AB  - PURPOSE: Palm and finger pulley anatomy has been well described in relation to
      osseous structures. The goal of this study was to describe skin surface markers
      that locate the underlying flexor tendon and pulley system. We describe the
      anatomic detail of these structures and provide a guide for the surgeon for
      making small incisions. Using this approach, extensile exposure can be avoided,
      and the integrity of the complex pulley system is maintained. METHODS: We
      dissected 12 palms and 48 fingers in 12 cadaver hands. We marked the palm and
      finger creases with methylene blue before dissection. We removed palm skin,
      finger skin, and subcutaneous tissue over the flexor tendon sheath and retained a
      2-mm strip of each skin crease in its native position. We divided the palm and
      palmar surface of the fingers into 4 distinct zones and measured the location of
      the proximal and distal extent of each pulley and the tendon anatomy relative to
      the proximal and distal skin crease. RESULTS: We documented the location of the
      proximal and distal extent of the annular and cruciate pulleys as well as the
      decussation of the flexor digitorum superficialis (FDS) tendon and Camper chiasm.
      The results allow us to establish a relationship between the skin creases and
      underlying anatomy by dividing the palm and finger into 4 zones. In zone A, in
      the palm, the A2 pulley is located in the distal third and the FDS decussation is
      at the proximal extent of the A2 pulley. Zone B is in the proximal phalanx and A2
      lies in the proximal third of this zone, whereas the Camper chiasm lies in the
      middle third. Zone C is in the middle phalanx and A4 and the insertion of FDS lie
      in the middle third of this zone. Zone D lies in the distal phalanx and the
      flexor digitorum profundus tendon inserts into the middle third of this zone.
      CONCLUSIONS: Skin creases can be used as surface markers to accurately locate the
      underlying pulley and tendon system and plan for limited incisions. CLINICAL
      RELEVANCE: These anatomic descriptions can aid surgeons in preoperative planning
      and may also help minimize the required exposure for flexor tendon repair and
      other surgery in the fingers and palm.

PMID- 22365713
TI  - Carpal tunnel release using the MANOS CTR system: preliminary results in 52
      patients.
AB  - PURPOSE: To describe a carpal tunnel release technique using the MANOS Carpal
      Tunnel Release device, with preliminary results in 52 patients. METHODS: The
      MANOS Carpal Tunnel Release device is a blade that divides the transverse carpal
      ligament using wrist and palm skin punctures. The awake patient provides feedback
      as the surgeon navigates a 2.1-mm-diameter blunt probe across the undersurface of
      the ligament from a wrist incision with standard disposable nerve stimulator
      monitoring. The leading tip of the blunt probe is uninsulated and conducts 2 mA.
      The surgeon converts the blunt insulated probe into an uninsulated blade by
      advancing a 0.9-mm needle through the palm with a thumb-activated deployment
      feature. The surgeon saws the ligament through the 2 skin punctures. We used a
      validated outcome questionnaire to assess postoperative symptoms at 3 months.
      RESULTS: Symptom severity and functional status scores compare favorably with
      literature controls for open and endoscopic surgery at 3 months. One patient
      required reoperation for incomplete release. There were no tendon or nerve
      injuries. CONCLUSIONS: Preliminary results suggest the MANOS Carpal Tunnel
      Release device to be safe and effective. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 22365714
TI  - Correction of varus heel pad in patients with Syme's amputations.
AB  - Syme's amputations can provide a reliable alternative to more proximal
      amputations, but they are not without their occasional complication. Varus heel
      pad migration has been well documented as a complication following Syme's
      amputations. We describe a technique of resection of soft tissue and bone
      combined with anchoring of the lateral band of the plantar fascia in order to
      treat patients with the complication of varus heel pad migration.

PMID- 22365715
TI  - Effect of ultraviolet radiation on photosynthesis, biomass, and fatty acid
      content and profile of a Scenedesmus rubescens-like microalga.
AB  - The effects of ultraviolet radiation (UVR) and nitrogen (NaNO(3)) concentration
      on photosynthesis, biomass, and fatty acid content and profile of a Scenedesmus
      rubescens-like microalga were measured in an outdoor 8-day culture study. UV
      induced photoinhibition decreased from 42.6% to 3.5%, in the presence of 75 mg/L
      NaNO(3) (HN) and from 52.9% to 22.6% in the presence of 7.5mg/L NaNO(3) (LN)
      nitrogen concentration, respectively. The concentrations of UV-absorbing
      compounds increased 4.3 and 4.9 times under HN and LN, respectively. Biomass
      accumulation was suppressed (10.7%) by UVR under HN, but not under LN conditions.
      Carotenoid content decreased from 1.05 +/- 0.06 to 0.96 +/- 0.15 (with UV
      radiation) and to 0.91 +/- 0.07 (without UV radiation), respectively, under HN,
      while it decreased to 0.05 +/- 0.04 (with UV radiation) and to 0.11 +/- 0.08
      (without UV radiation), respectively, under LN. The content of C18:1n9 fatty
      acids increased by about 430%, whereas that of C18:3n3 decreased by about 65% in
      both radiation treatments during nitrogen starvation. The results showed that the
      absence of UVR screening does not change the fatty acid content and profile of S.
      rubescens-like algae cultivated outdoors under HN and LN conditions.

PMID- 22365716
TI  - Carbon neutral electricity production by Synechocystis sp. PCC6803 in a microbial
      fuel cell.
AB  - The aim of this work was to illustrate the use of photosynthetic microbes in a
      microbial fuel cell to produce electricity without the requirement of an external
      carbon source. This research here describes the use of a cyanobacterium
      Synechocystis PCC6803, to produce electricity without any net CO(2) production in
      a two-chambered MFC. Conditions for optimum electricity production were
      determined through standardizing operating parameters. A maximum power density of
      6.7mWm(-3)(anode chamber volume) was achieved under high intensity lighting
      (10,000lux). Light intensity and wavelength directly affected electricity
      production, indicating the pivotal role played by photosynthesis. The maximum
      removal of CO(2) was 625mmolm(-3) over 20h under high intensity light. The
      results presented here will contribute to the understanding of how cyanobacteria
      can be exploited for the direct conversion of CO(2) to electric current.

PMID- 22365717
TI  - Application of T-DNA insertional mutagenesis for improving cellulase production
      in the filamentous fungus Trichoderma reesei.
AB  - A T-DNA-tagged mutant library created by Agrobacterium-mediated transformation
      (AMT) was assayed for improvement of cellulase production. After 96-well plate
      screening for rapid growth on cellulose substrates followed by plate-clearing
      zone assay, three putative mutants, TA-32, TB-87 and TE-6, with enhanced
      cellulolytic ability were isolated, exhibiting 38%, 51% and 31% increase in total
      cellulase activity than the parental strain QM9414, respectively. Endoglucanase,
      cellobiohydrolase and beta-glucosidase activities as well as the hydrolysis
      efficiencies of the mutants were also improved. Moreover, T-DNA was shown to be
      integrated at a single site in the genomes of TA-32 and TE-6 while inserted at
      two copies into the genome of TB-87. Further, the sequences flanking the T-DNA
      insertion sites were successfully rescued, demonstrating the increased utility of
      T-DNA insertional mutagenesis for improvement of cellulase production as well as
      subsequent identification of the tagged genes relevant to cellulolytic ability.

PMID- 22365718
TI  - Diversity of a mesophilic lignocellulolytic microbial consortium which is useful
      for enhancement of biogas production.
AB  - A mesophilic lignocellulolytic microbial consortium BYND-5, established by
      successive subcultivation, was applied to enhance the biogas production. The
      degradation efficiency of BYND-5 for rice straw was more than 49.0 +/- 1.8% after
      7 days of cultivation at 30 degrees C. Various organic compounds, including
      acetic acid, propionic acid, butyric acid and glycerin were detected during
      biodegradation. The diversity analysis of BYND-5 was conducted by ARDRA
      (Amplified ribosomal DNA restriction analysis) of the 16S rDNA clone library.
      Results indicated that bacterial groups represented in the clone library were the
      Firmicutes (5.96%), the Bacteroidetes (40.0%), Deferribacteres (8.94%),
      Proteobacteria (16.17%), Lentisphaerae (2.13%), Fibrobacteraceae (1.7%), and
      uncultured bacterium (25.1%). Additionally, the enhancement of biogas yield and
      methane content was directly related to the pretreatment with BYND-5. The
      microbial community identified herein is potential candidate consortium for the
      degradation of waste lignocellulose and enhancement of biogas production under
      the mesophilic temperature conditions.

PMID- 22365719
TI  - [Responses by neuropaediatricians to a palliative care questionnaire].
AB  - INTRODUCTION: Up to 70% of children currently treated by Palliative Care Units in
      Europe are neurological patients. Our objective is to assess the knowledge,
      interest and involvement in Paediatric Palliative Care (PPC) among Spanish
      paediatric neurologists. MATERIAL AND METHODS: We contacted 297
      Neuropaediatricians by and attached a 10-question multiple choice test. This
      questionnaire was related to the level of knowledge of PPC, identification of
      patients requiring this specific care, involvement of a paediatric neurologist,
      use of local palliative resources, and formal training in this subject. RESULTS:
      Participation rate was 32% (96/297). Around 90% knew the definition of PPC, could
      identify patients with a short-term survival prognosis, and had treated children
      who eventually died due to their illnesses. A "non resuscitation order" had been
      written by 61% of them at least once; 77% considered the patients home as the
      preferred location of death (if receiving appropriate care), 9% preferred the
      hospital, and 14% had no preference for any of these options. Just over half
      (52%) had contacted local PC resources, and 61% had referred or would refer
      patients to be seen periodically by both services (PC and Paediatric Neurology).
      More than half (55%) consider themselves not trained enough to deal with these
      children, and 80% would like to increase their knowledge about PPC. CONCLUSION:
      The paediatric neurologists surveyed frequently deal with children who suffer
      from incurable diseases. Their level of involvement with these patients is high.
      However, there is an overwhelming necessity and desire to receive more training
      to support these children and their families.

PMID- 22365720
TI  - Determination of the boar taint compound skatole in meat juice by means of stable
      isotope dilution analysis-direct immersion-solid phase microextraction-gas
      chromatography/mass spectrometry.
AB  - A novel SIDA-DI-SPME-GC/MS procedure for the quantitation of skatole in pork meat
      juice was developed and validated as a substitute for back fat sample analysis.
      System suitability was evaluated by determining the correlation between skatole
      concentrations in a subset of 38 paired meat juice and back fat samples selected
      from 90 fattened boars. High correlation was observed between both matrices and
      conclusions about the partitioning of skatole as well as of androstenone between
      fat and lean compartments in vivo were drawn.

PMID- 22365721
TI  - Adding the spatial dimension to the social network analysis of an epidemic:
      investigation of the 2007 outbreak of equine influenza in Australia.
AB  - Equine influenza is a highly contagious and widespread viral respiratory disease
      of horses and other equid species, characterised by fever and a harsh dry cough.
      In 2007, in the first reported outbreak in Australia, the virus spread through
      the horse populations of two states within 4 months. Most of the geographic
      spread occurred within the first 10 days and was associated with the movement of
      infected horses prior to the implementation of movement controls. This study
      applies social network analysis to describe spread of equine influenza between
      horse premises infected in the early outbreak period, identifying spread
      occurring through a contact network and secondary local spatial spread. Social
      networks were constructed by combining contact-tracing data on horse movements
      with a distance matrix between all premises holding horses infected within the
      first 10 days of the outbreak. These networks were analysed to provide a
      description of the epidemic, identify premises that were central to disease
      spread and to estimate the relative proportion of premises infected through
      infected horse movements and through local spatial spread. We then explored the
      effect of distance on disease spread by estimating the range of local spread
      (through direct contact, transmission on fomites and windborne transmission)
      based on the level of fragmentation in the network and also by directly
      estimating the shape of the outbreak's spatial transmission kernel. During the
      first 10 days of this epidemic, 197 horse premises were infected; 70 of these
      were included in the contact-traced network. Most local spread occurred within 5
      km. Local spread was estimated to have occurred up to a distance of 15.3 km -
      based on the contact-and-proximity network - and at a very low incidence beyond
      this distance based on the transmission kernel estimate. Of the 70 premises in
      the contact network, spread to 14 premises (95% CI: 9, 20 premises) was likely to
      have occurred through local spatial spread from nearby infected premises,
      suggesting that 28.3% of spread in the early epidemic period was 'network
      associated' (95% CI: 25.6, 31.0%). By constructing a 'maximal network' of contact
      and proximity (based on a distance cut-off of 15.3 km), 44 spatial clusters were
      described, and the horse movements that initiated infection in these locations
      were identified. Characteristics of the combined network, incorporating both
      spatial and underlying contact relationships between infected premises, explained
      the high rate of spread, the sequence of cluster formation and the widespread
      dispersal experienced in the early phase of this epidemic. These results can
      inform outbreak control planning by guiding the imposition of appropriate control
      zone diameters around infected premises and the targeting of surveillance and
      interventions.

PMID- 22365723
TI  - A rare occurrence of hepatocellular carcinoma metastasis to the mandible: report
      of a case and review of the literature.

PMID- 22365722
TI  - Stability after mandibular setback: mandible-only versus 2-jaw surgery.
AB  - PURPOSE: The objective of this study was to evaluate whether changes in the
      technique for mandibular setback surgery since the introduction of rigid internal
      fixation have improved postoperative stability in Class III correction with
      setback alone and 2-jaw surgery. PATIENTS AND METHODS: Cephalometric (skeletal
      and dental) outcomes for 17 patients with mandibular setback alone were compared
      with outcomes in 83 patients with 2-jaw surgery for Class III correction.
      Demographic characteristics in the 2 groups were similar, and the mean amount of
      setback (-4.7 mm) was the same; however, given a mean maxillary advancement of
      4.9 mm, the 2-jaw patients had a greater total Class III correction. RESULTS:
      Greater than 4 mm of posterior movement of the gonion at surgery and a resulting
      significant change in ramus inclination were found in 8 of the mandible-only
      patients (47%) but only 1 of the 2-jaw patients (1%). Postoperatively, the mean
      changes for the 2 groups were similar, with mean forward movement of the chin
      (pogonion) of 2.8 mm in both groups, but the mechanism was different. In the
      mandible-only patients, the major reason for forward movement of the chin was
      recovery of ramus inclination. In the 2-jaw group, about half the change in chin
      position was because of forward movement of the gonion; the other half was
      because of small upward movement of the maxilla that allowed upward-forward
      rotation of the mandible. In both groups there was a significant correlation (r =
      0.42, P < .0001) between postoperative change in the position of the chin and
      gonion. CONCLUSIONS: Despite improvements in surgical techniques for mandibular
      setback since 1995, postoperative stability still leaves something to be desired,
      but there is better control of the ramus position when 2-jaw surgery is
      performed.

PMID- 22365724
TI  - University of Washington oral and maxillofacial surgery program.

PMID- 22365725
TI  - Biliary cast syndrome in a non-transplant patient with acute pancreatitis.

PMID- 22365726
TI  - Amygdala lesion profoundly alters altruistic punishment.

PMID- 22365727
TI  - Evidence for shared susceptibility to epilepsy and psychosis: a population-based
      family study.
AB  - BACKGROUND: There is emerging evidence of an etiological overlap between a range
      of neurodevelopmental disorders, including schizophrenia and epilepsy. Here we
      investigate shared familial vulnerability to psychotic illness and epilepsy in a
      family-based study. METHODS: The study population consisted of parents and their
      children born in Helsinki between 1947 and 1990. The Finnish Hospital Discharge
      Register was used to determine psychiatric and neurological outcomes in adulthood
      for all offspring. Parental history of psychosis and epilepsy was determined by
      linking the Hospital Discharge Register and the Finnish Population Register.
      RESULTS: Our total sample comprised 9653 families and 23,404 offspring.
      Individuals with epilepsy had a 5.5-fold increase in the risk of having a broadly
      defined psychotic disorder, an almost 8.5-fold increase in the risk of having
      schizophrenia, and a 6.3-fold increase in the risk of having bipolar disorder.
      There was strong evidence of clustering of the association between epilepsy and
      psychosis within families. Individuals with a parental history of epilepsy had a
      2-fold increase in the risk of developing psychosis, compared with individuals
      without a parental history of epilepsy. Individuals with a parental history of
      psychosis had, reciprocally, a 2.7-fold increase in the risk of having a
      diagnosis of generalized epilepsy, compared with individuals without a parental
      history of psychosis. Post hoc analyses showed that these associations were not
      driven by the comorbidity of epilepsy and psychosis in the parents. CONCLUSIONS:
      These findings support recent evidence of overlapping etiological factors between
      epilepsy and schizophrenia, especially recent evidence of a genetic overlap
      between these disorders.

PMID- 22365728
TI  - Bacterial lysates as a potentially effective approach in preventing acute
      exacerbation of COPD.
AB  - The use of bacterial lysates to reduce acute exacerbations of COPD (AECOPDs) is
      an intriguing concept. Bacterial lysates are powerful inducers of a specific
      immune response against bacterial infections, but their mechanism of action is
      not fully understood. Apparently, they lower bacterial carriage levels in the
      respiratory tract, decrease the incidence and severity of exacerbations, decrease
      hospitalizations owing to exacerbations, and reduce the need for antibiotics.
      Unfortunately, almost all trials conducted to date are small and methodologically
      flawed. Further studies are needed to produce a greater level of evidence that
      can support the recommendation for a more widely use of bacterial lysates as a
      prophylactic treatment of AECOPDs.

PMID- 22365729
TI  - p38 MAPK inhibitors, IKK2 inhibitors, and TNFalpha inhibitors in COPD.
AB  - COPD represents a major respiratory disorder, causing significant morbidity and
      mortality throughout the world. While therapies exist for COPD, they are not
      always effective, and many patients experience exacerbations and morbidity
      despite current therapies. Study of the molecular mechanisms involved in the
      underlying physiological manifestations of COPD has yielded multiple new targets
      for therapeutic intervention. In this review, we discuss signaling pathways
      involved in COPD pathogenesis and review clinical studies of p38 MAPK inhibitors,
      TNFalpha inhibitors, and IKK2 inhibitors as potential COPD therapies.

PMID- 22365730
TI  - Vitamin D modulates airway smooth muscle function in COPD.
AB  - COPD is a disease manifested as persistent airflow obstruction with an enhanced
      inflammatory response in the airways and lungs to noxious particles and gases
      which evokes symptoms of dyspnea on exertion, cough and mucus production. Airway
      smooth muscle plays a central role in the COPD diathesis and is implicated in
      many aspects of COPD pathogenesis. Vitamin D deficiency has been associated with
      COPD severity and studies suggest a role for Vitamin D as a treatment for COPD.
      In this review, we describe the effects of 1,25-dihydroxyvitamin D on airway
      smooth muscle function, including agonist-induced shortening, secretion of
      inflammatory mediators, and myocyte hypertrophy and hyperplasia.

PMID- 22365731
TI  - Determination of lutein by high-performance thin-layer chromatography using
      densitometry and screening of major dietary carotenoids in food supplements.
AB  - The main problem in the densitometric determination of carotenoids is their rapid
      degradation during and immediately after chromatography, respectively. In this
      study, we show that 15 ng of lutein, lycopene and beta-carotene standards applied
      on C(18) RP high-performance thin-layer chromatography (HPTLC) plates pre
      developed with dichloromethane-methanol 1:1 (v/v) remained stable for 1h after
      the development of chromatogram using methanol-acetone 1:1 (v/v) with 0.1% of 2
      tert-butylhydroquinone (TBHQ), which is a substantial improvement of their
      stability. An HPTLC quantification procedure for free lutein, with densitometry
      at 450 nm based on the developed method described above, was established and
      validated. Repeatabilities of the chromatography expressed by the relative
      standard deviation (RSD) from 6 applications of lutein standard at 5, 15 and 25
      ng were 3.41, 1.33 and 1.65%, respectively. The best fit calibration curve from 5
      ng to 30 ng of lutein was polynomial. Limit of detection (1.5 ng) and limit of
      quantification (5 ng) were the best achieved so far. With these chromatographic
      conditions dietary carotenoids lutein esters, lycopene, free lutein and beta
      carotene from food supplements were also well separated and were identified by
      visible absorption spectra scanned in situ and by mass spectra. Some additional
      developing solvents with the same type of chromatographic layer are proposed for
      the fast separation of lutein esters from free lutein in food supplements.

PMID- 22365733
TI  - Let's make it happen: the role of let-7 microRNA in development.
AB  - Noncoding RNAs have emerged as an integral part of posttranscriptional gene
      regulation. Among that class of RNAs are the microRNAs (miRNAs), which
      posttranscriptionally regulate target mRNAs containing complementary sequences.
      The broad presence of miRNAs in lower eukaryotes, plants, and mammals highlights
      their importance throughout evolution. MiRNAs have been shown to regulate many
      pathways, including development, and disruption of miRNA function can lead to
      disease (Ivey and Srivastava, 2010; Jiang et al., 2009). Although the first miRNA
      genes were discovered in the nematode, Caenorhabditis elegans, almost 20 years
      ago, the field of miRNA research began when they were found in multiple organisms
      a little over a decade ago (Lagos-Quintana et al., 2001; Lau et al., 2001; Lee
      and Ambros, 2001; Lee et al., 1993; Pasquinelli et al., 2000; Wightman et al.,
      1993). Here, we review one of the first characterized miRNAs, let-7, and describe
      its role in development and the intricacies of its biogenesis and function.

PMID- 22365732
TI  - Hepcidin is correlated to soluble hemojuvelin but not to increased GDF15 during
      pregnancy.
AB  - Increased maternal and foetal iron requirements during pregnancy are compensated
      by an increase of intestinal iron absorption. Animal studies have shown that the
      expression of the main iron regulator hepcidin is significantly suppressed during
      pregnancy, but the factors associated with hepcidin suppression remain unknown.
      To investigate possible suppressors of hepcidin expression during pregnancy we
      determined serum concentrations of growth-differentiation factor-15 (GDF15),
      erythropoietin (EPO), soluble hemojuvelin (HJV) and hepcidin in 42 pregnant women
      at different time points of gestation and correlated them with serum iron and
      haematological parameters. Serum iron parameters and serum hepcidin concentration
      significantly decreased during pregnancy, whereas serum concentrations of GDF15,
      EPO and soluble HJV significantly increased. A negative correlation of hepcidin
      with EPO and soluble HJV but no correlation between hepcidin and GDF15 was found.
      Hepcidin and ferritin were positively correlated throughout the pregnancy. Our
      findings suggest that hepcidin expression is controlled by body iron stores where
      soluble HJV and EPO may act as suppressors of hepcidin.

PMID- 22365734
TI  - Evolution, expression, and developmental function of Hox-embedded miRNAs.
AB  - Exquisite regulation of Hox protein activity is fundamental to the
      regionalization of the early embryo across diverse taxa. Highlighting the
      critical importance of these transcription factors, an astonishing number of
      different mechanisms have evolved to tightly coordinate their activity both in
      time and in space. The recent identification of numerous microRNAs that are not
      only embedded within Hox clusters but also target numerous Hox genes suggests an
      important role for these regulatory molecules in shaping Hox protein output.
      Here, we discuss the positioning of these miRNAs within clusters over
      evolutionary time, the unexpected complexity in miRNA processing and target
      interactions, and the current understanding of Hox-embedded miRNA function during
      development.

PMID- 22365735
TI  - The role of microRNAs in muscle development.
AB  - MicroRNAs play essential roles during animal development, including in developing
      muscle. Many microRNAs are expressed during muscle development and some, like miR
      1 and miR-133, are muscle specific. Muscle microRNAs are integrated into myogenic
      regulatory networks: their expression is under the transcriptional and
      posttranscriptional control of myogenic factors, and they in turn have widespread
      control of muscle gene expression. This review summarizes recent work
      characterizing the function of microRNAs in muscle biology and specifically
      focuses on the genetic analysis of muscle microRNAs in a variety of model
      organisms including worms, flies, zebrafish, and mice.

PMID- 22365736
TI  - Small RNAs in germ cell development.
AB  - The identification of small RNA molecules and the elucidation of their functions
      in the cell enhanced our understanding of the mechanisms controlling gene
      expression at the posttranscriptional level. Here, we review findings concerning
      the role small RNA molecules play in the development of the germline in various
      organisms. In this context, microRNAs (miRNAs) function predominantly in
      regulating mRNA expression and turnover and direct the expression of specific
      proteins to founders of the germline, the primordial germ cells (PGCs). miRNA
      function is then important for the maintenance of germline stem cells (GSCs) in
      their niche and for coordinating GSC differentiation into the gametes. The second
      family of small RNA molecules, the short endo-siRNAs, regulate gene expression
      posttranscriptionally as well but are also important for transposable elements
      regulation and thus for genome stability. Last, the Piwi-interacting small RNAs
      (piRNAs) are specifically expressed in the germline, where they primarily control
      transposon activity, guarding the genome from potential damage associated with
      excessive transposition. Together, the function of these three groups of small
      RNAs ensures proper development and continuation of the germline through the
      generations.

PMID- 22365737
TI  - Diverse functions of microRNAs in nervous system development.
AB  - MicroRNAs (miRNAs) are integral parts of the gene regulatory networks that
      control most developmental processes. Through their regulatory action, miRNAs
      introduce an additional layer of genetic complexity that can translate into
      increased cellular diversity, something that is extremely relevant to nervous
      system structure. In addition, miRNAs sharpen the spatial and temporal boundaries
      between different cellular states during development. Here, we illustrate these
      roles with a number of specific miRNAs that act during distinct steps of neural
      development. We further discuss specific aspects of miRNA function that make
      these regulators particularly suited to provide the robustness and complexity
      that are essential for the dynamic nature of both the development and activity of
      the nervous system.

PMID- 22365738
TI  - MicroRNAs and hematopoietic cell development.
AB  - Hematopoiesis is a dynamic and highly complex developmental process that gives
      rise to a multitude of the cell types that circulate in the blood of
      multicellular organisms. These cells provide tissues with oxygen, guard against
      infection, prevent bleeding by clotting, and mediate inflammatory reactions.
      Because the hematopoietic system plays such a central role in human diseases such
      as infections, cancer, autoimmunity, and anemia, it has been intensely studied
      for more than a century. This scrutiny has helped to shape many of the
      developmental paradigms that exist today and has identified specific protein
      factors that serve as master regulators of blood cell lineage specification.
      Despite this progress, many aspects of blood cell development remain obscure,
      suggesting that novel layers of regulation must exist. Consequently, the
      emergence of regulatory noncoding RNAs, such as the microRNAs (miRNAs), is
      beginning to provide new insights into the molecular control networks underlying
      hematopoiesis and diseases that stem from aberrations in this process. This
      review will discuss how miRNAs fit into our current understanding of
      hematopoietic development in mammals and how breakdowns in these pathways can
      trigger disease.

PMID- 22365739
TI  - A miR image of stem cells and their lineages.
AB  - MicroRNAs (miRs) comprise a class of tiny (~19-24 nucleotide), noncoding RNAs
      that regulate gene expression posttranscriptionally. Since the discovery of the
      founding members lin-4 and let-7 as key regulators in the developing nematode,
      miRs have been found throughout the eukaryotic kingdom. Functions for miRs are
      wide-ranging and encompass embryogenesis, stem cell biology, tissue
      differentiation, and human diseases including cancers. In this chapter, we begin
      by acquainting our readers with miRs and introducing them to their biogenesis.
      Then, we focus on the roles of miRs in stem cells during tissue development and
      homeostasis. We use mammalian skin as our main paradigm, but we also consider miR
      functions in several different types of adult stem cells. We conclude by
      discussing future challenges that will lead to a comprehensive understanding of
      miR functions in stem cells and their lineages.

PMID- 22365742
TI  - Understanding how miRNA genes function in metazoan development. Preface.

PMID- 22365741
TI  - Biological robustness and the role of microRNAs: a network perspective.
AB  - Over the past decade, microRNA molecules have emerged as critical regulators in
      the expression and function of animal genomes. This review discusses the
      relationship between microRNA-mediated regulation and the robustness of
      biochemical networks that contain microRNAs. Most biochemical networks are
      robust; they are relatively insensitive to the precise values of reaction
      constants and concentrations of molecules acting within the network. MicroRNAs
      involved in network robustness may appear to be nonessential under favourable
      uniform conditions used in conventional laboratory experiments. However, the
      function of these molecules can be revealed under environmental and genetic
      perturbations. Recent advances have revealed unexpected features of microRNA
      organization in networks that help explain their promotion of robustness.

PMID- 22365740
TI  - Exploiting Drosophila genetics to understand microRNA function and regulation.
AB  - Although a great deal is known about the identity, biogenesis, and targeting
      capacity of microRNAs (miRNAs) in animal cells, far less is known about their
      functional requirements at the organismal level. Much remains to be understood
      about the necessity of miRNAs for overt phenotypes, the identity of critical
      miRNA targets, and the control of miRNA transcription. In this review, we provide
      an overview of genetic strategies to study miRNAs in the Drosophila system,
      including loss- and gain-of-function techniques, genetic interaction strategies,
      and transgenic reporters of miRNA expression and activity. As we illustrate the
      usage of these techniques in intact Drosophila, we see certain recurrent themes
      for miRNA functions, including energy homeostasis, apoptosis suppression, growth
      control, and regulation of core cell signaling pathways. Overall, we hope that
      this exposition of Drosophila genetic techniques, well known to the legions of
      fly geneticists and used to study all genes, can inform the general miRNA
      community that focuses on other biochemical, molecular, computational, and
      structural avenues. Clearly, it is the combination of these myriad techniques
      that has accelerated miRNA research to its extraordinary pace.

PMID- 22365743
TI  - Cacogeusia following pine nut ingestion: a six patient case series.
AB  - This is a retrospective case series of 6 patients complaining of a bad taste
      (cacogeusia) specifically metallogeusia, following the ingestion of pine nuts.(1)
      The taste arose always within 48h of ingestion, and in all but one patient
      spontaneously resolved within 14 days. Pine nuts also have a potential for
      triggering anaphylaxis.(2).

PMID- 22365744
TI  - The microvascular thenar flap as a new possibility for super-thin soft tissue
      reconstruction in the oral cavity--initial clinical results.
AB  - We report the first clinical use of a free microvascular thenar flap for
      reconstruction of intraoral soft tissues. In 9 patients with a recurrent oral
      squamous cell carcinoma (SCC), a new primary oral SCC, or a defect of the hard
      palate after radiotherapy, we covered the soft tissue defect, after resection of
      the tumour or local preparation, with a microvascular thenar flap. All patients
      had had combined resection and irradiation for treatment of the initial tumour.
      In every case the thenar flap was harvested from the left forearm. Arteries were
      anastomosed to cervical arteries on either side. The veins were anastomosed to
      the deep jugular or subclavian vein. Patients were followed up clinically after
      3, 6, and 12 months and radiologically every 6 months. The mean length of the
      pedicle was 21 cm. The mean width of the flap was 27 mm (range 24-30) and the
      mean length 37 mm (range 26-49). All anastomoses worked well. All flaps healed
      without major complications. A thin but stable layer of soft tissue resulted in
      every case. All patients were able to wear their prostheses. Good functional and
      aesthetic results were seen at each follow-up visit, and there were no signs of
      relapse. The microvascular thenar flap is well-suited for reconstruction of thin
      layers of soft tissue in the oral cavity. The long pedicle and hairlessness are
      also ideal for covering intraoral defects after previous operations and in necks
      with few if any vessels. Primary wound closure is possible in many cases.

PMID- 22365745
TI  - Deep hypothermia terminates status epilepticus--an experimental study.
AB  - In search for novel treatment approaches in status epilepticus, the
      anticonvulsant effect of moderate and deep hypothermia was assessed in a rodent
      model. Self-sustaining status epilepticus (SSSE) characterized by spontaneous
      high-amplitude discharges recorded from the dentate gyrus was induced in male
      adult rats by electrical stimulation of the perforant path. After the end of
      stimulation, rats underwent cooling to 30  degrees C (n=7) and 20  degrees C
      (n=10) for 120 min and rewarming to 37  degrees C for another 60 min. Control
      SSSE animals (n=6) remained untreated for 180 min. Frequency of epileptiform
      discharges was assessed every 10 min. At the target temperature of 20  degrees C,
      SSSE was completely suppressed in four rats, this effect was not observed in any
      animal of the other two groups (p=0.043). On rewarming, seizure activity did not
      reoccur. Discharge frequency was significantly lower in the 20  degrees C group
      at most time points after 60 min of cooling. Following deep hypothermia, eight
      animals were rewarmed, all survived and moved spontaneously at 37  degrees C.
      These experimental data indicate the strong and enduring anticonvulsant and
      obviously safe properties of cooling down to 20  degrees C. Patients with status
      epilepticus refractory to first- and second-line anticonvulsants may benefit from
      deep cooling as an effective non-pharmacological adjunct to anesthetic
      anticonvulsants.

PMID- 22365746
TI  - Moderating effects of music on resting state networks.
AB  - Resting state networks (RSNs) are spontaneous, synchronous, low-frequency
      oscillations observed in the brains of subjects who are awake but at rest. A
      particular RSN called the default mode network (DMN) has been shown to exhibit
      changes associated with neurological disorders such as temporal lobe epilepsy or
      Alzheimer's disease. Previous studies have also found that differing experimental
      conditions such as eyes-open versus eyes-closed can produce measurable changes in
      the DMN. These condition-associated changes have the potential of confounding the
      measurements of changes in RSNs related to or caused by disease state(s). In this
      study, we use fMRI measurements of resting-state connectivity paired with EEG
      measurements of alpha rhythm and employ independent component analysis,
      undirected graphs of partial spectral coherence, and spatiotemporal regression to
      investigate the effect of music-listening on RSNs and the DMN in particular. We
      observed similar patterns of DMN connectivity in subjects who were listening to
      music compared with those who were not, with a trend toward a more introspective
      pattern of resting-state connectivity during music-listening. We conclude that
      music-listening is a valid condition under which the DMN can be studied.

PMID- 22365748
TI  - Direct microRNA detection with universal tagged probe and time-resolved
      fluorescence technology.
AB  - microRNAs have emerged as the central player in gene expression regulation and
      have been considered as potent cancer biomarkers for early disease diagnosis.
      Direct microRNA detection without amplification and labeling is highly desired.
      Here we present a rapid, sensitive and selective microRNA detection method based
      on the base stacking hybridization coupling with time-resolved fluorescence
      technology. Other than planar microarrays, magnetic beads are used as reaction
      platforms. In this method, one universal tag is used to report all microRNA
      targets. Its specificity allows for discrimination between microRNAs differing by
      a single nucleotide, and between precursor and mature microRNAs. This method also
      provides a high sensitivity down to 20 fM. Moreover, the full protocol can be
      completed in about 3 h starting from total RNA.

PMID- 22365749
TI  - An aptamer based competition assay for protein detection using CNT activated gold
      interdigitated capacitor arrays.
AB  - An aptamer can specifically bind to its target molecule, or hybridize with its
      complementary strand. A target bound aptamer complex has difficulty to hybridize
      with its complementary strand. It is possible to determine the concentration of
      target based on affinity separation system for the protein detection. Here, we
      exploited this property using C-reactive protein (CRP) specific RNA aptamers as
      probes that were immobilized by physical adsorption on carbon nanotubes (CNTs)
      activated gold interdigitated electrodes of capacitors. The selective binding
      ability of RNA aptamer with its target molecule was determined by change in
      capacitance after allowing competitive binding with CRP and complementary RNA
      (cRNA) strands in pure form and co-mixtures (CRP:cRNA=0:1, 1:0, 1:1, 1:2 and
      2:1). The sensor showed significant capacitance change with pure forms of
      CRP/cRNA while responses reduced considerably in presence of CRP:cRNA in co
      mixtures (1:1 and 1:2) because of the binding competition. At a critical CRP:cRNA
      ratio of 2:1, the capacitance response was dramatically lost because of the
      dissociation of adsorbed aptamers from the sensor surface to bind when excess
      CRP. Binding assays showed that the immobilized aptamers had strong affinity for
      cRNA (K(d)=1.98 MUM) and CRP molecules (K(d)=2.4 MUM) in pure forms, but low
      affinity for CRP:cRNA ratio of 2:1 (K(d)=8.58 MUM). The dynamic detection range
      for CRP was determined to be 1-8 MUM (0.58-4.6 MUg/capacitor). The approach
      described in this study is a sensitive label-free method to detect proteins based
      on affinity separation of target molecules that can potentially be used for
      probing molecular interactions.

PMID- 22365747
TI  - Concordance of MEG and fMRI patterns in adolescents during verb generation.
AB  - In this study we focused on direct comparison between the spatial distributions
      of activation detected by functional magnetic resonance imaging (fMRI) and
      localization of sources detected by magnetoencephalography (MEG) during identical
      language tasks. We examined the spatial concordance between MEG and fMRI results
      in 16 adolescents performing a three-phase verb generation task that involves
      repeating the auditorily presented concrete noun and generating verbs either
      overtly or covertly in response to the auditorily presented noun. MEG analysis
      was completed using a synthetic aperture magnetometry (SAM) technique, while the
      fMRI data were analyzed using the general linear model approach with random
      effects. To quantify the agreement between the two modalities, we implemented
      voxel-wise concordance correlation coefficient (CCC) and identified the left
      inferior frontal gyrus and the bilateral motor cortex with high CCC values. At
      the group level, MEG and fMRI data showed spatial convergence in the left
      inferior frontal gyrus for covert or overt generation versus overt repetition,
      and the bilateral motor cortex when overt generation versus covert generation.
      These findings demonstrate the utility of the CCC as a quantitative measure of
      spatial convergence between two neuroimaging techniques.

PMID- 22365750
TI  - Paraoxonase1 deficiency in mice is associated with hypotension and increased
      levels of 5,6-epoxyeicosatrienoic acid.
AB  - AIM: Serum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its
      association with hypertension is controversial. We studied the possible role of
      PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice.
      METHODS AND RESULTS: Both, systolic and diastolic BPs were lower in PON1KO
      compared to WT mice. Hypotension detected in PON1KO is probably neither related
      to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or
      aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt
      diet, BP was further reduced in PON1KO mice. The later, pointed to a possible
      involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed,
      administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP.
      The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT.
      However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4
      specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6
      EET levels were further elevated under high-salt diet or administration of
      arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in
      increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in
      elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in
      vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol.
      Vasodilation, blocked by excess of dietary K(+) but not reversed by depletion of
      cellular Ca(2+) stores, point to endothelial-derived hyperpolarization-like
      response. CONCLUSION: The present study shows causal, direct relationship between
      PON1 and blood pressure which is mediated, at least in part, by the regulation of
      5,6-EET.

PMID- 22365751
TI  - Synthesis and evaluation of a new series of 1'-cyclobutyl-6-(4
      piperidyloxy)spiro[benzopyran-2,4'-piperidine] derivatives as high affinity and
      selective histamine-3 receptor (H3R) antagonists.
AB  - A novel class of 1'-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4'
      piperidine] derivatives with low nanomolar affinity for the human and rat
      histamine-3 receptors (H(3)Rs) are described. The spirobenzopyran piperidine
      ether analogs demonstrated excellent H(3)R affinity and selectivity against
      histamine receptor subtypes (H(1)R, H(2)R, and H(4)R), were stable in liver
      microsomes, and had selectivity against CYP P450 enzymes. Compounds 10, 13, 15,
      and 16 demonstrated high H(3)R affinity, in vitro liver microsomal stability,
      selectivity against CYP isoforms, moreover, these ether analogs exhibited
      acceptable iv pharmacokinetic (PK) properties but had poor oral exposure in rat.

PMID- 22365752
TI  - Novel N'-benzylidene benzofuran-3-carbohydrazide derivatives as antitubercular
      and antifungal agents.
AB  - Tuberculosis constitutes today a serious threat to human health worldwide,
      aggravated by the increasing number of identified multi-drug resistant strains of
      Mycobacterium tuberculosis (Mtb), its causative agent, as well as by the lack of
      development of novel mycobactericidal compounds for the last few decades. A novel
      series of benzofuran-3-carbohydrazide and its analogs was synthesized and
      characterized spectroscopically. All the compounds were characterized and
      screened for in vitro anti-tuberculosis (anti-TB) activity against Mycobacterium
      tuberculosis H37Rv strains by using resazurin assay utilizing microtiter-plate
      method (REMA). These compounds also showed good antifungal activity against
      Candida albicans. Thus, the high level of activity shown by the compounds (8a,
      8k) suggests that these compounds could serve as leads for development of novel
      synthetic compounds with enhanced anti-TB and antifungal activity.

PMID- 22365753
TI  - Relationship between structure and P-glycoprotein inhibitory activity of dimeric
      peptides related to the Dmt-Tic pharmacophore.
AB  - To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to
      an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their
      P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized,
      N(alpha),N(epsilon)-[(CH(3))(2)Mle-Tic](2)Lys-NH(2) and its D-Lys analog were
      found to exhibit potent P-gp inhibitory activity, twice that of verapamil, in
      doxorubicin-resistant K562 cells. Structure-activity studies indicated that the
      correct hydrophobicity and spacer length between two aromatic rings are important
      structural elements in this series of analogs for inhibition of P-gp.

PMID- 22365754
TI  - Identification and evaluation of apoptotic compounds from Garcinia oligantha.
AB  - Four new compounds, oliganthins A-D (1-4), and one known caged xanthone
      gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The
      structures of the new compounds were elucidated by spectroscopic evidences. All
      of the five compounds were evaluated for their apoptosis-inducing effects using
      HeLa-C3 cells which have been genetically engineered to produce a fluorescent
      biosensor capable of detecting caspase-3 activation. All of them induced cell
      apoptosis at 10 MUM or lower concentrations. The apoptotic activity of
      oliganthins A, B and gaudichaudione H were further confirmed by detecting the
      cleavage of PARP, which is the substrate of activated caspase-3, in these
      compounds-treated cells using the method of Western blot. Moreover, the values of
      IC(50) were measured for all five compounds on HeLa cells using the MTT assay.
      Among them, gaudichaudione H had the lowest IC(50) value of 0.90 MUM, while the
      other four new compounds had IC(50) values of 1.58, 1.52, 4.15, and 7.82 MUM,
      respectively. These results show that gaudichaudione H has the strongest
      apoptosis-inducing effect and cell growth inhibition effect among these xanthones
      and it may have the potential to be developed into a new anticancer agent.

PMID- 22365755
TI  - Discovery of potent, selective, and metabolically stable 4-(pyridin-3
      yl)cinnolines as novel phosphodiesterase 10A (PDE10A) inhibitors.
AB  - We report the discovery of 6,7-dimethoxy-4-(pyridin-3-yl)cinnolines as novel
      inhibitors of phosphodiesterase 10A (PDE10A). Systematic examination and analyses
      of structure-activity-relationships resulted in single digit nM potency against
      PDE10A. X-ray co-crystal structure revealed the mode of binding in the enzyme's
      catalytic domain and the source of selectivity against other PDEs. High in vivo
      clearance in rats was addressed with the help of metabolite identification (ID)
      studies. These findings combined resulted in compound 39, a promising potent
      inhibitor of PDE10A with good in vivo metabolic stability in rats and efficacy in
      a rodent behavioral model.

PMID- 22365756
TI  - Sesquiterpenoids from Atractylodes macrocephala act as farnesoid X receptor and
      progesterone receptor modulators.
AB  - Two sesquiterpenoids, atractylenolide II and III, were isolated and identified
      from Atractylodes macrocephala (Asteraceae) to be subsequently evaluated for
      their activity against farnesoid X receptor (FXR) and progesterone receptor (PR)
      by transient transfection reporter assays. These sesquiterpenoids did not exert
      significant agonistic effect but antagonized the activity of chenodeoxycholic
      acid (CDCA), an endogenous FXR agonist, for FXR driven SHP promoter
      transactivation. Additionally, they transactivated CYP7A1 gene promoter activity
      by antagonizing FXR. Apart from acting as a FXR antagonist, atractylenolide III
      also showed agonistic activity against PR. All these results demonstrated that
      atractylenolide II and III are the active components of Atractylodes macrocephala
      to exert specific pharmacologic effects.

PMID- 22365757
TI  - Molecular modeling study of cyclic pentapeptide CXCR4 antagonists: new insight
      into CXCR4-FC131 interactions.
AB  - CXCR4 is a G-protein coupled receptor that is associated with many diseases such
      as breast cancer metastasis, HIV infection, leukemic disease and rheumatoid
      arthritis, and is thus considered an attractive drug target. Previously, we
      identified a cyclic pentapeptide, FC131, that is a potent antagonist for CXCR4.
      In this study, we constructed a three dimensional model of the CXCR4-FC131
      complex. To investigate the backbone flexibility of FC131, we performed molecular
      dynamics simulations of FC131 based on the NMR structure of FC131, and obtained
      snapshot structures from the trajectories which were used to model the docking
      pose of FC131 into CXCR4. Our final model of the CXCR4-FC131 complex is partially
      different from the X-ray crystal structure of CXCR4-CVX15 and suggests water
      mediated interactions. Nevertheless, this docking pose is consistent with the
      experimental data. We believe our model will aid in the discovery and development
      of small-molecule antagonists for CXCR4.

PMID- 22365758
TI  - Identification and optimization of small molecule antagonists of vasoactive
      intestinal peptide receptor-1 (VIPR1).
AB  - Identification, synthesis and structure-activity relationship of small-molecule
      VIPR1 antagonists encompassing two chemical series are described.

PMID- 22365759
TI  - Catalysis by molecular iodine: a rapid synthesis of 1,8-dioxo-octahydroxanthenes
      and their evaluation as potential anticancer agents.
AB  - Molecular iodine facilitated the reaction of 5,5-dimethyl-1,3-cyclohexanedione
      with aromatic aldehydes in iso-propanol affording a variety of 1,8-dioxo
      octahydroxanthenes in high yields. Most of the compounds synthesized showed good
      anti-proliferative properties in vitro against three cancer cell lines and 9-(2
      hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)
      dione possessing a 2-hydroxy phenyl group at C-9 position was found to be
      promising. Further structure elaboration of the same compound and the crystal
      structure analysis and hydrogen bonding patterns of another compound that is, 9
      (4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)
      dione prepared by using this methodology is presented.

PMID- 22365760
TI  - Pyrrolovesamicols--synthesis, structure and VAChT binding of two 4-fluorobenzoyl
      regioisomers.
AB  - This Letter describes the synthesis of two regioisomers of a new class of
      vesamicol analogs as possible ligands for imaging the vesicular acetylcholine
      transporter in future PET studies. The two pyrrolovesamicols (+/-)-6a and (+/-)
      6b were synthesized by nucleophilic ring opening reaction of a tetrahydroindole
      epoxide precursor with 4-phenylpiperidine. The reaction mechanism of the
      synthesis was studied by HPLC and the molecular structures were determined by X
      ray structure analysis. Unexpected low binding affinities to VAChT (K(i)=312+/-73
      nM for (+/-)-6a and K(i)=7320+/-1840 nM for (+/-)-6b) were determined by
      competitive binding analysis using a cell line stably transfected with ratVAChT
      and (-)-[(3)H]vesamicol.

PMID- 22365761
TI  - New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low
      affinity for the offtarget cytosolic isoform II.
AB  - Considering phenols and coumarins as lead molecules for obtaining non-sulfonamide
      inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1), we screened a large number
      of compounds possessing diverse chemotypes, but structural features which
      resemble the two chemical classes. Here we report an investigation of such
      derivatives which do not significantly inhibit CA II, but show interesting
      inhibition profiles against other isozymes. Pyridine-N-oxide-2-thiophenol,
      thiobenzoic acid, thimerosal, two oximes derived from a six-membered-ring lactone
      and from coumarin; 2-hydroxyquinoline and coumaphos, were investigated as
      inhibitors of CA I-XIV. All these compounds did not inhibit CA II, whereas the
      two oximes and 2-hydroxyquinoline were low nanomolar inhibitors of CA I, IX, XII,
      XIII and XIV, showing a very different inhibition profile compared to
      sulfonamides and sulfamates. Some other compounds showed low micromolar
      inhibition of other isoforms of interest, such as CA VA/VB, CA VI and VII. This
      study demonstrates that a rather wide range of structures show low nanomolar
      micromolar inhibitory activity against many CA isozymes, without inhibiting
      significantly the offtarget isoform CA II.

PMID- 22365762
TI  - Pyridyl aminothiazoles as potent Chk1 inhibitors: optimization of cellular
      activity.
AB  - Translation of significant biochemical activity of pyridyl aminothiazole class of
      Chk1 inhibitors into functional CEA potency required analysis and adjustment of
      both physical properties and kinase selectivity profile of the series. The steps
      toward optimization of cellular potency included elimination of CDK7 activity,
      reduction of molecular weight and polar surface area and increase in
      lipophilicity of the molecules in the series.

PMID- 22365763
TI  - [Present and future of echography in spondyloarthritis].
AB  - Today ultrasound in spondyloarthritis is being developed in three main areas.
      Joint ultrasound is similar to that described in rheumatoid arthritis and other
      synovitis, with extensive literature on the matter. Enthesis ultrasound has a
      growing number of publications that describe the main elementary lesions. Several
      ultrasound enthesis scores have been developed that provide an overall view of
      the patient status and this information is useful both in the field of diagnosis
      and in assessing disease activity. The sacroiliac joints have also received
      attention and the published sensitivity and specificity could be useful in
      clinical practice. The future is unknown, but ultrasound has many possibilities
      that include improving the reliability, the incorporation of enthesis ultrasound
      assessment to the diagnostic classification criteria as well as the likelyhood
      developing simplified scores.

PMID- 22365764
TI  - Struggling for independence: a grounded theory study on convalescence of ICU
      survivors 12 months post ICU discharge.
AB  - OBJECTIVES: To explore and explain the challenges, concerns, and coping
      modalities in ICU-survivors living with a partner or spouse during the first 12
      months post ICU discharge. DESIGN: Qualitative, longitudinal grounded theory
      study. SETTINGS: Five ICUs in Denmark, four general, one neurosurgical. METHODS:
      Thirty-five interviews with patients and their partners at three and 12 months
      post ICU discharge plus two group interviews with patients only and two with
      partners only. FINDINGS: The ICU survivors struggled for independence and
      focussed chiefly on 'recovering physical strength', 'regaining functional
      capacity', and 'resuming domestic roles'. The first year of recovery evolved in
      three phases characterised by training, perseverance and continued hope for
      recovery. The ICU survivors did not seem to worry about traumatic experiences.
      Rather, their focus was on a wide range of other aspects of getting well.
      CONCLUSION: The study offers new insight into post-ICU convalescence emphasising
      patients' motivation for training to recover. The findings may contribute to
      defining the best supportive measures and timing of rehabilitation interventions
      in ICU and post ICU that may help ICU-survivors in their struggle for
      independence throughout recovery.

PMID- 22365765
TI  - Critical care nurses' judgement of pain status: a case study design.
AB  - In the performance of their professional activities, critical care nurses
      routinely make important judgements based on uncertain, fallible and inter
      substitutable data. It is anticipated that this study will make visible the
      strategy by which critical care nurses use and combine multiple fallible cues, of
      which little is known, to reach a judgement about the pain status of the
      ventilated patient after coronary artery bypass graft (CABG) surgery. The study
      was conducted in one intensive care unit in a large university hospital with
      thirty critical care nurses and thirty ventilated patients. Nurses providing care
      for critically ill ventilated patients post CABG surgery were asked to think
      aloud, whilst the researcher simultaneously observed patient pain behaviours. For
      the purposes of this article, two contrasting pain episodes will be presented,
      namely, incident pain related to repositioning (initial hour) versus pain at rest
      (five hours later) post CABG surgery. Critical care nurses utilised different
      combinations of pain cues to make a judgement that the ventilated patient was
      either at 'risk for acute pain' during repositioning (initial hour) or was 'in
      acute pain' at rest (five hours) post CABG surgery. The combinations were: a
      'primary preventative pain cue pattern' and a 'pain behaviour cue pattern', which
      were reliant on the critical care nurse's constant surveillance at the bedside
      linked with a theoretical and practical understanding of how pain, against a
      background of rapidly changing haemodynamics, could lead to a swift deterioration
      in a ventilated patient post CABG surgery.

PMID- 22365766
TI  - General principles of retrovirus vector design.
AB  - An understanding in the life cycle of gamma-retroviruses has led to significant
      progress in the development of murine leukemia virus (MLV)-based vectors for gene
      delivery and human gene therapy. An MLV-based vector consists of the cis-acting
      sequences important for viral replication and gene expression. The sequence that
      encodes viral proteins is replaced with the gene of interest. To generate
      infectious retroviral vectors, viral-encoded proteins are supplied in trans for
      virion assembly. Here, we describe a method to rapidly generate MLV vectors from
      transiently transfected human 293T cells. The strategies to purify and titer the
      vector and to detect the presence of replication competent retrovirus (RCR) in
      the vector harvest are also described.

PMID- 22365767
TI  - Strategies for retrovirus-based correction of severe, combined immunodeficiency
      (SCID).
AB  - Severe combined immunodeficiencies (SCIDs) appear as optimal disease targets to
      challenge potential efficacy of gene therapy. Ex vivo, retrovirally mediated gene
      transfer into hematopoietic progenitor cells has been shown to provide sustained
      correction of two forms of SCID, that is, SCID-X1 and adenosine deaminase
      deficiencies. In the former case, however, genotoxicity was observed in a
      minority of patients as a consequence of retroviral integration into proto
      oncogenes loci and transactivation. Design of vectors in which the enhancer
      element of retroviral LTR has been deleted and an internal promoter added (self
      inactivated vectors) could provide both safe and efficient gene transfer as being
      presently tested.

PMID- 22365768
TI  - Retrovirus and lentivirus vector design and methods of cell conditioning.
AB  - Retroviruses are useful tools for the efficient delivery of genes to mammalian
      cells, owing to their ability to stably integrate into the host cell genome. Over
      the past few decades, retroviral vectors have been used in gene therapy clinical
      trials for the treatment of a number of inherited diseases and cancers. The
      earliest retrovirus vectors were based on simple oncogenic gammaretroviruses such
      as Moloney murine leukemia virus (MMLV) which, when pseudotyped with envelope
      proteins from other viruses such as the gibbon ape leukemia virus envelope
      protein (GALV) or vesicular stomatitis virus G protein (VSV-G), can efficiently
      introduce genes to a wide range of host cells. However, gammaretroviral vectors
      have the disadvantage that they are unable to efficiently transduce nondividing
      or slowly dividing cells. As a result, specific protocols have been developed to
      activate cells through the use of growth factors and cytokines. In the case of
      hematopoietic stem cells, activation has to be carefully controlled so that
      pluripotency is maintained. For many applications, gammaretroviral vectors are
      being superseded by lentiviral vectors based on human immunodeficiency virus type
      1 (HIV-1) which has additional accessory proteins that enable integration in the
      absence of cell division. In addition, retroviral and lentiviral vector design
      has evolved to address a number of safety concerns. These include separate
      expression of the viral genes in trans to prevent recombination events leading to
      the generation of replication-competent viruses. Further, the development of self
      inactivating (SIN) vectors reduces the potential for transactivation of
      neighboring genes and allows the incorporation of regulatory elements that may
      target gene expression more physiologically to particular cell types.

PMID- 22365769
TI  - Analysis of the clonal repertoire of gene-corrected cells in gene therapy.
AB  - Gene therapy-based clinical phase I/II studies using integrating retroviral
      vectors could successfully treat different monogenetic inherited diseases.
      However, with increased efficiency of this therapy, severe side effects occurred
      in various gene therapy trials. In all cases, integration of the vector close to
      or within a proto-oncogene contributed substantially to the development of the
      malignancies. Thus, the in-depth analysis of integration site patterns is of high
      importance to uncover potential clonal outgrowth and to assess the safety of gene
      transfer vectors and gene therapy protocols. The standard and nonrestrictive
      linear amplification-mediated PCR (nrLAM-PCR) in combination with high-throughput
      sequencing exhibits technologies that allow to comprehensively analyze the clonal
      repertoire of gene-corrected cells and to assess the safety of the used vector
      system at an early stage on the molecular level. It enables clarifying the
      biological consequences of the vector system on the fate of the transduced cell.
      Furthermore, the downstream performance of real-time PCR allows a quantitative
      estimation of the clonality of individual cells and their clonal progeny. Here,
      we present a guideline that should allow researchers to perform comprehensive
      integration site analysis in preclinical and clinical studies.

PMID- 22365770
TI  - Developing novel lentiviral vectors into clinical products.
AB  - Gene therapy vectors based on murine retroviruses have now been in clinical
      trials for over 20 years. During that time, a variety of novel vector pseudotypes
      were developed in an effort to improve gene transfer. Lentiviral vectors are now
      in clinical trials and a similar evolution of vector technology is anticipated.
      These modifications present challenges for those producing large-scale clinical
      materials. This chapter discusses approaches to process development for novel
      lentiviral vectors, highlight considerations, and methods to be incorporated into
      the development schema.

PMID- 22365771
TI  - Lentivirus vectors in beta-thalassemia.
AB  - Patients with beta-thalassemia major require lifelong transfusions and iron
      chelation, regardless of the type of causative mutations (e.g., beta0,
      beta(E)/beta0). The only available curative therapy is allogeneic hematopoietic
      transplantation, although most patients do not have an HLA-matched, geno
      identical donor, and those who do still risk graft-versus-host disease. Hence,
      gene therapy by ex vivo transfer of a functional beta-globin gene is an
      attractive novel therapeutic modality. In beta-thalassemia, transfer of a
      therapeutic globin gene does not confer a selective advantage to transduced stem
      cells, and complex DNA regulatory sequences have to be present within the
      transfer vector for proper expression. This is why lentiviral vectors have proven
      especially suited for this application, and the first Phase I/II human clinical
      trial was initiated. Here, we report on the first gene therapy patient with
      severe beta(E)/beta0-thalassemia, who has become transfusion-independent, and
      provide methods and protocols used in the context of this clinical trial.

PMID- 22365772
TI  - Gene therapy for chronic granulomatous disease.
AB  - Mutations in phagocyte NADPH oxidase cause CGD, resulting in recurrent infections
      and granulomatous inflammation. Hematopoietic stem cell (HSC) transplant can cure
      CGD, but most patients lack a suitable donor. We conducted a clinical trial of ex
      vivo autologous HSC gene transfer as salvage therapy for three patients with X
      linked CGD (X-CGD) who had incurable infection. Patients received
      nonmyeloablative busulfan conditioning and then were infused with amphotropic
      MFGS-gp91phox murine retrovirus vector-transduced autologous HSC, resulting in
      early gene marking and high-level oxidase function correction of 24%, 5%, and 4%
      of circulating neutrophils. Subjects #1 and #3 fully resolved infection and have
      maintained gene marking at 5 years at 0.7% and 0.03% oxidase-normal neutrophils.
      Subject #2 lost gene marking by 4 weeks and at 6 months succumbed to his
      infection. The two surviving subjects have normal blood count and bone marrow
      exam, with no evidence for clonal dominance of vector inserts. We conclude that
      gene therapy salvage treatment for severe infection unresponsive to conventional
      therapy can provide life-saving clinical benefit to CGD patients lacking a
      suitable donor. We are developing lentivectors for our next generation gene
      therapy of CGD. We are also exploring novel alternate approaches to gene therapy
      using zinc finger nuclease-mediated gene targeting of induced pluripotent stem
      cells derived from CGD patients.

PMID- 22365773
TI  - Alternative splicing caused by lentiviral integration in the human genome.
AB  - Gene transfer vectors derived from murine oncoretroviruses or human lentiviruses
      are widely used in human gene therapy. Integration of these vectors in the human
      genome may, however, have genotoxic effects, caused by deregulation of gene
      expression at the transcriptional or posttranscriptional level. In particular,
      integration of lentiviral vectors within transcribed genes has a significant
      potential to affect their expression by interfering with splicing and
      polyadenylation of primary transcripts. Aberrant splicing is caused by the usage
      of both constitutive and cryptic splice sites located in the retroviral backbone
      as well as in the gene expression cassettes. We describe a set of simple methods
      that allow the identification of chimeric transcripts generated by the insertion
      of a lentiviral vector within genes and the evaluation of their relative
      abundance. Identification of the splice sites, either constitutive or cryptic,
      that are frequently used by the cell splicing machinery within a given vector
      provides a useful resource to attempt recoding of the vector with the objective
      of reducing its potential genotoxicity in a clinical context.

PMID- 22365774
TI  - Genotoxicity assay for gene therapy vectors in tumor prone Cdkn2a-/- mice.
AB  - Integrative viral vectors are able to efficiently transduce hematopoietic stem
      progenitor cells allowing stable transgene expression in the entire hematopoietic
      system upon transplant in conditioned recipients. For these reasons, integrative
      vectors based on gamma-retroviruses and lentiviruses have been successfully used
      in gene therapy clinical trials for the treatment of genetic diseases, especially
      blood disorders. However, in different gamma-retroviral-based clinical trials,
      vector integration into the host cell genome triggered oncogenesis by a mechanism
      called insertional mutagenesis. Thus, a thorough reassessment of the safety of
      available gene transfer systems is a crucial outstanding issue for the whole gene
      therapy field. Sensitive preclinical models of vector genotoxicity are
      instrumental to achieve a more detailed understanding of the factors that
      modulate the risks of insertional mutagenesis. Here, we will describe the
      methodologies used to address the mutagenesis risk of vector integration using a
      murine in vivo genotoxicity assay based on transduction and transplantation of
      tumor-prone hematopoietic stem and progenitor cells.

PMID- 22365775
TI  - Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a severe genetic demyelinating disease
      caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette
      transporter encoded by the ABCD1 gene. When performed at an early stage of the
      disease, allogeneic hematopoietic stem cell transplantation (HCT) can arrest the
      progression of cerebral demyelinating lesions. To overcome the limitations of
      allogeneic HCT, hematopoietic stem cell (HSC) gene therapy strategy aiming to
      perform autologous transplantation of lentivirally corrected cells was developed.
      We demonstrated the preclinical feasibility of HSC gene therapy for ALD based on
      the correction of CD34+ cells from X-ALD patients using an HIV1-derived
      lentiviral vector. These results prompted us to initiate an HSC gene therapy
      trial in two X-ALD patients who had developed progressive cerebral demyelination,
      were candidates for allogeneic HCT, but had no HLA-matched donors or cord blood.
      Autologous CD34+ cells were purified from the peripheral blood after G-CSF
      stimulation, genetically corrected ex vivo with a lentiviral vector encoding wild
      type ABCD1 cDNA, and then reinfused into the patients after they had received
      full myeloablative conditioning. Over 3 years of follow-up, the hematopoiesis
      remained polyclonal in the two patients treated with 7-14% of granulocytes,
      monocytes, and T and B lymphocytes expressing the lentivirally encoded ALD
      protein. There was no evidence of clonal dominance or skewing based on the
      retrieval of lentiviral insertion repertoire in different hematopoietic lineages
      by deep sequencing. Cerebral demyelination was arrested 14 and 16months,
      respectively, in the two treated patients, without further progression up to the
      last follow-up, a clinical outcome that is comparable to that observed after
      allogeneic HCT. Longer follow-up of these two treated patients and HSC gene
      therapy performed in additional ALD patients are however needed to evaluate the
      safety and efficacy of lentiviral HSC gene therapy in cerebral forms of X-ALD.

PMID- 22365776
TI  - Retroviral replicating vectors in cancer.
AB  - The use of replication-competent viruses for the treatment of cancer is an
      emerging technology that shows significant promise. Among the various different
      types of viruses currently being developed as oncolytic agents, retroviral
      replicating vectors (RRVs) possess unique characteristics that allow highly
      efficient, non-lytic, and tumor-selective gene transfer. By retaining all of the
      elements necessary for viral replication, RRVs are capable of transmitting genes
      via exponential in situ amplification. Their replication-competence also provides
      a powerful means whereby novel and useful RRV variants can be generated using
      natural selection. Their stringent requirement for cell division in order to
      achieve productive infection, and their preferential replication in cells with
      defective innate immunity, confer a considerable degree of natural specificity
      for tumors. Furthermore, their ability to integrate stably into the genome of
      cancer cells, without immediate cytolysis, contributes to long-lasting
      therapeutic efficacy. Thus, RRVs show much promise as therapeutic agents for
      cancer and are currently being tested in the clinic. Here we describe
      experimental methods for their production and quantitation, for adaptive
      evolution and natural selection to develop novel or improved RRV, and for in
      vitro and in vivo assessment of the therapeutic efficacy of RRVs carrying prodrug
      activator genes for treatment of cancer.

PMID- 22365777
TI  - Adeno-associated virus vectorology, manufacturing, and clinical applications.
AB  - Adeno-associated virus (AAV) has emerged as an attractive vector for gene
      therapy. The benefits of using AAV for gene therapy include long-term gene
      expression, the inability to autonomously replicate without a helper virus,
      transduction of dividing and nondividing cells, and the lack of pathogenicity
      from wild-type infections. A number of Phase I and Phase II clinical trials
      utilizing AAV have been carried out worldwide (Aucoin et al., 2008; Mueller and
      Flotte, 2008). A number of challenges have been identified based upon data
      generated from these clinical trials. These challenges include (1) large scale
      manufacturing technologies in accordance with current Good Manufacturing
      Practices (cGMP), (2) tissue specific tropism of AAV vectors, (3) high
      quality/high potency recombinant AAV vectors (rAAV), and (4) immune response to
      AAV capsids and transgene. In this chapter, we will provide an overview of AAV
      biology, AAV vectorology, rAAV manufacturing, and the current status on the
      latest rAAV clinical trials.

PMID- 22365779
TI  - Generation of hairpin-based RNAi vectors for biological and therapeutic
      application.
AB  - RNA interference (RNAi) is a natural process of gene silencing mediated by small
      RNAs. Shortly after the discovery of the RNAi mechanism, scientists devised
      various methods of delivering small interfering RNAs (siRNAs) capable of co
      opting the endogenous RNAi machinery and suppressing target gene expression based
      on sequence complementarity. RNAi has since become a powerful tool to study gene
      function and is being investigated as a potential therapeutic approach to treat a
      vast array of human diseases (e.g., cancer, viral infections, and dominant
      genetic disorders). Among the available RNAi vectors are hairpin-based expression
      platforms (short-hairpin RNAs and artificial microRNAs) designed to mimic
      endogenously expressed inhibitory RNAs. These RNAi vectors are capable of
      achieving long-term potent gene silencing in vitro and in vivo. Here, we describe
      methods to design and generate these hairpin-based vectors and briefly review
      considerations for downstream applications.

PMID- 22365778
TI  - Gene delivery to the retina: from mouse to man.
AB  - With the recent progress in identifying disease-causing genes in humans and in
      animal models, there are more and more opportunities for using retinal gene
      transfer to learn more about retinal physiology and also to develop therapies for
      blinding disorders. Success in preclinical studies for one form of inherited
      blindness have led to testing in human clinical trials. This paves the way to
      consider a number of other retinal diseases as ultimate gene therapy targets in
      human studies. The information presented here is designed to assist scientists
      and clinicians to use gene transfer to probe the biology of the retina and/or to
      move appropriate gene-based treatment studies from the bench to the clinic.

PMID- 22365780
TI  - Recombinant adeno-associated viral vector reference standards.
AB  - Reference standard materials (RSMs) exist for a variety of biologics including
      vaccines but are not readily available for gene therapy vectors. To date, a
      recombinant adeno-associated virus serotype 2 RSM (rAAV2 RSM) has been produced
      and characterized and was made available to the scientific community in 2010. In
      addition, a rAAV8 RSM has been produced and will be characterized in the coming
      months. The use of these reference materials by members of the gene therapy field
      facilitates the calibration of individual laboratory vector-specific internal
      standards and the eventual comparison of preclinical and clinical data based on
      common dosage units. Normalization of data to determine therapeutic dose ranges
      of rAAV vectors for each particular tissue target and disease indication is
      important information that can enhance the safety and protection of patients.

PMID- 22365781
TI  - NIH oversight of human gene transfer research involving retroviral, lentiviral,
      and adeno-associated virus vectors and the role of the NIH recombinant DNA
      advisory committee.
AB  - In response to public and scientific concerns regarding human gene transfer
      research, the National Institutes of Health (NIH) developed a transparent
      oversight system that extends to human gene transfer protocols that are either
      conducted with NIH funding or conducted at institutions that receive NIH funding
      for recombinant DNA research. The NIH Recombinant DNA Advisory Committee (RAC)
      has been the primary advisory body to NIH regarding the conduct of this research.
      Human gene transfer research proposals that are subject to the NIH Guidelines for
      Research Involving Recombinant DNA Molecules (NIH Guidelines) must be submitted
      to the NIH Office of Biotechnology Activities (OBA), and protocols that raise
      novel scientific, safety, medical, ethical, or social issues are publicly
      discussed at the RAC's quarterly public meetings. OBA also convenes gene transfer
      safety symposia and policy conferences to provide a public forum for scientific
      experts to discuss emerging issues in the field. This transparent system of
      review promotes the rapid exchange of important scientific information and
      dissemination of data. The goal is to optimize the conduct of individual research
      protocols and to advance gene transfer research generally. This process has
      fostered the development of retroviral, lentiviral, and adeno-associated viral
      vector mediated gene delivery.

PMID- 22365782
TI  - Regulatory structures for gene therapy medicinal products in the European Union.
AB  - Taking into account the complexity and technical specificity of advanced therapy
      medicinal products: (gene and cell therapy medicinal products and tissue
      engineered products), a dedicated European regulatory framework was needed.
      Regulation (EC) No. 1394/2007, the "ATMP Regulation" provides tailored regulatory
      principles for the evaluation and authorization of these innovative medicines.
      The majority of gene or cell therapy product development is carried out by
      academia, hospitals, and small- and medium-sized enterprises (SMEs). Thus,
      acknowledging the particular needs of these types of sponsors, the legislation
      also provides incentives for product development tailored to them. The European
      Medicines Agency (EMA) and, in particular, its Committee for Advanced Therapies
      (CAT) provide a variety of opportunities for early interaction with developers of
      ATMPs to enable them to have early regulatory and scientific input. An important
      tool to promote innovation and the development of new medicinal products by micro
      , small-, and medium-sized enterprises is the EMA's SME initiative launched in
      December 2005 to offer financial and administrative assistance to smaller
      companies. The European legislation also foresees the involvement of
      stakeholders, such as patient organizations, in the development of new medicines.
      Considering that gene therapy medicinal products are developed in many cases for
      treatment of rare diseases often of monogenic origin, the involvement of patient
      organizations, which focus on rare diseases and genetic and congenital disorders,
      is fruitful. Two such organizations are represented in the CAT. Research networks
      play another important role in the development of gene therapy medicinal
      products. The European Commission is funding such networks through the EU Sixth
      Framework Program.

PMID- 22365783
TI  - The successful clinical use of viral vectors for human gene therapy. Preface.

PMID- 22365784
TI  - Outcome measures for primary Sjogren's syndrome.
AB  - Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the
      pathological hallmark of primary Sjogren's syndrome, whereas involvement of
      salivary and lachrymal glands with the clinical counterpart of dry eye and dry
      mouth are the predominant features of the disease, together with fatigue and
      musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin
      vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a
      consistent number of patients. As result, clinical features in SS can be divided
      into two facets: the benign subjective but disabling manifestations such as
      dryness, pain and fatigue, and the systemic manifestations. In the past decades,
      a core set of domains, which included sicca symptoms, objective measurements of
      tear and saliva production, fatigue, quality of life, disease activity and damage
      was indicated as essential for outcome assessment in this disorder. Afterwards,
      great efforts have been made to develop valid tools for the assessment of
      different domains. Specific questionnaires such as the Profile of Fatigue and
      Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI) have been proposed as
      dedicated tools for the evaluation of patients symptoms, whereas different
      composite indexes have been suggested for the assessment of disease activity and
      damage. Some of these preliminary studies served as bases of an international
      project supported by EULAR, aimed at developing two consensus disease activity
      indexes: the EULAR Sjogren's Syndrome Patients Reported Index (ESSPRI), and the
      EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), a systemic activity
      index to assess systemic manifestations. A detailed and critical review of all
      these indexes is provided in this article. Both EULAR indexes showed, in recent
      studies, to be feasible, valid, and reliable instruments. After their final
      validation, which is currently in process, they could be used as consensus
      outcome criteria in therapeutic trials and in clinical practice.

PMID- 22365785
TI  - Potentially autoreactive naturally occurring transitional T3 B lymphocytes
      exhibit a unique signaling profile.
AB  - B lymphocytes exhibit phenotypic differences that correlate with their
      developmental or functional stages and affect humoral immune responses. One
      recently described subset of naturally occurring immature transitional type 3
      (T3) B lymphocytes is believed to consist of potentially autoimmune cells whose
      signaling properties have not been studied in detail. This study characterizes
      intracellular signaling in T3 B cells in wildtype C57BL/6 mice. Protein
      phosphorylation and Ca(2+) responses upon B-cell antigen receptor (BCR)
      engagement were measured by multicolor flow cytometry. We observed high baseline
      signaling activity and reduced BCR-mediated responses in T3 cells, which
      confirmed their anergy - a functional state in which lymphocytes recognize
      chronically present self-antigens but cannot produce immune response due to
      intrinsic signaling inhibition. Our results also revealed a previously unknown T3
      specific phosphorylation pattern of 24 key signaling molecules involved in BCR
      signal transduction. These characteristics reflect the balance between
      stimulatory and inhibitory BCR signaling pathways in anergy. Results obtained in
      the collagen-induced arthritis model demonstrate the loss of anergy in T3 B cells
      during the onset of the disease. Our findings provide rationale for further
      investigating alterations in B-cell signaling patterns as earliest functional
      biomarkers of changes in the immune tolerance of autoreactive B cells.

PMID- 22365786
TI  - Implementation of an automated system for monitoring adherence to hemodialysis
      treatment: a report of seven years of experience.
AB  - OBJECTIVE: In this paper we present the clinical deployment and evaluation of a
      computerized system, EMOSTAT, aimed at improving the quality of hemodialysis
      sessions. EMOSTAT automatically imports data from the hemodialysis monitoring
      software tools and analyzes the delivered treatment looking at six clinically
      relevant parameters. Failures-to-adhere (FtAs) to the planned treatment are
      detected and reported to the care-givers. METHODS: EMOSTAT has been used for more
      than seven years in the management of a dialysis service located in Mede, Italy.
      A total of 72 patients were monitored and 21251 dialyses were collected. Data
      analysis is performed on the periods 2002-2005 and 2005-2008, corresponding to
      two different software releases. RESULTS: The system had been exploited into
      everyday clinical practice for the entire considered period. The number of FtAs
      significantly decreased along the first period: the bulk blood flow FtAs
      decreased after the introduction of the system. Hemodialysis sessions lasted
      longer in the second period. Co-occurring FtAs, highlighting the presence of
      complex FtAs patterns, were also detected. CONCLUSIONS: EMOSTAT provides an
      effective way to re-focus the attention of the dialysis department on the
      treatment plan and on its implementation. The automatic data collection and the
      design philosophy of EMOSTAT allowed the routine use of the system.

PMID- 22365787
TI  - Development and validation of the Compensatory Eating and Behaviors in Response
      to Alcohol Consumption Scale (CEBRACS).
AB  - The goal of the current investigation was to develop and validate a measure to
      assess an individual's eating-related behaviors related to alcohol consumption,
      specifically behaviors intended to compensate for calories so that more alcohol
      could be consumed or restrict calories to enhance the psychoactive effects of
      alcohol consumption. Two hundred and seventy four undergraduate students (n=51
      males; 75.2% Caucasian) completed a newly developed scale, the Compensatory
      Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS), along
      with measures of eating restriction, bulimia, and body dissatisfaction. An
      exploratory factor analysis on the CEBRACS revealed the existence of 4 clear-cut
      factors: alcohol effects, bulimia, dieting and exercise, and restriction.
      Internal consistency statistics for all subscales ranged from .79 to .95. Pearson
      product-moment correlations between the CEBRACS and measures of bulimia,
      restriction, and body dissatisfaction ranged from .04 to .44. T-tests revealed no
      gender differences in compensatory eating behaviors. Future research directions
      and limitations of the current study are discussed.

PMID- 22365788
TI  - An examination of dieting behaviors among adults: links with depression.
AB  - In the current study, we examined predictors of healthy and unhealthy dieting
      behaviors with the aim of examining whether or not weight control strategies are
      associated with depression. Men and women (N=198; M=24.80 years; 51% women) were
      recruited from a university campus and its surrounding community in the
      northeastern US. Participants' height and weight were measured, and they
      completed a survey on health behaviors and attitudes. Results indicated that
      women and men with high BMIs were more likely to engage in both healthy and
      unhealthy dieting behaviors than those with low BMIs. Additionally, women with
      higher levels of depressive symptoms utilized fewer healthy dieting behaviors and
      more unhealthy dieting behaviors. Depression was not linked to healthy or
      unhealthy dieting behaviors in men. These findings are discussed in terms of the
      potential reciprocal relationship between women's unhealthy weight control
      strategies and depression.

PMID- 22365789
TI  - Investigating the use of the Mizes Anorectic Cognitions Questionnaire in a
      community sample of racially diverse high school males and females.
AB  - There are relatively few assessment devices which have been developed to measure
      the cognitions or cognitive processes of the eating disordered pathology of
      adolescents. One promising scale is the Mizes Anorectic Cognitions Questionnaire,
      and its revised version (MAC; MAC-R). The present study examined scores on the
      MAC and MAC-R in a racially diverse sample consisting of 201 non-clinical
      adolescents. The goals of this study were (1) to examine the reliability and
      validity of the MAC and MAC-R in a heretofore unexamined population, adolescents,
      and (2) to examine scores across sex, race, and weight classification in
      adolescents in order to determine whether normative data should be further
      stratified into these groups. Findings of the study suggest that the MAC and MAC
      R are internally consistent, reliable, and strongly related to other well
      established instruments. The present study also suggests that separate means and
      standard deviations be used when determining nonclinical male and female
      adolescent normative scores. There were no significant differences on scores
      across race and weight classification thus further stratification is not advised.

PMID- 22365790
TI  - The role of experiential avoidance, rumination and mindfulness in eating
      disorders.
AB  - Anorexia nervosa has been associated with high levels of ruminative thoughts
      about eating, shape and weight as well as avoidance of emotion and experience.
      This study examined the associations between disorder-specific rumination,
      mindfulness, experiential avoidance and eating disorder symptoms. A sample of
      healthy females (n=228) completed a battery of on-line self-report measures. A
      hierarchical regression analysis revealed that ruminative brooding on eating,
      weight and shape concerns was uniquely associated with eating disorder symptoms,
      above and beyond anxiety and depression symptoms. In a small group (n=42) of
      individuals with a history of anorexia nervosa, only reflection on eating weight
      and shape was able to predict eating disorder symptoms when controlling for
      depression and anxiety. The results suggest that rumination (both brooding and
      reflection) on eating, weight and shape concerns may be a process which
      exacerbates eating disorder symptoms. Examining rumination may improve
      understanding of the cognitive processes which underpin anorexia nervosa and this
      may in turn aid the development of novel strategies to augment existing
      interventions. Replication in a larger clinical sample is warranted.

PMID- 22365791
TI  - Deconstructing the concept of the healthy eater self-schematic: relations to
      dietary intake, weight and eating cognitions.
AB  - This study investigated differences in dietary intake, weight status, food
      preoccupation, and attributions about healthy eating lapses between individuals
      classified as healthy eater self-schematics and nonschematics. The study also
      assessed whether the separate dimensions of the self-schema construct (self
      description as a healthy eater and perceived importance of being a healthy eater
      to self-image) are related to these health outcomes. College students (N=125; 82%
      female) completed questionnaires assessing healthy eater self-schema status,
      dietary intake, weight status, food preoccupation, and lapse attributions.
      Results revealed that females who were classified as healthy eater self
      schematics ate more fruits and vegetables, ate less junk food and had lower BMIs
      than nonschematics. Healthy eater self-schematics also engaged in more positive
      thoughts and fewer negative thoughts about food, made less stable attributions
      about lapses in healthy eating and endorsed more personal control over lapses.
      When the two dimensions of the self-schema were examined separately, self
      description appeared to be more related to these outcomes than perceived
      importance.

PMID- 22365792
TI  - Stepped-care in obesity treatment: matching treatment intensity to participant
      performance.
AB  - This investigation examined the effectiveness of a self-help (SH), stepped-care
      (SC) weight loss program. Based on a failure to achieve pre-assigned weight loss
      goals, participants were eligible to be stepped-up from a SH program to two
      levels of treatment intensity (weight loss group [WLG]; individual counseling
      [IC]) beyond SH. The primary outcome was change in body weight. Fifty-three
      overweight/obese adults (BMI>=27 kg/m(2); mean BMI of 37.3, SD=6.6, 89%
      Caucasian, and 77% female) participated in an 18-week weight loss intervention.
      During several phases of the investigation, those stepped-up to more intensive
      treatment lost comparable weight to those who were not stepped-up. Nevertheless,
      by the end of treatment, individuals who remained in SH (M=8.6%) lost a
      significantly greater percentage of weight than individuals who received SH+IC
      (M=4.7%; p<.05) and individuals in SH+IC lost a significantly greater percentage
      of weight than individuals who received SH+WLG+IC (M=1.6%; p<.05). While some
      individuals benefited from being stepped-up to greater intensity treatment, other
      individuals experienced little benefit. The application of SC principles to the
      treatment of obesity needs further study.

PMID- 22365793
TI  - Adolescent aesthetic athletes: a group at risk for eating pathology?
AB  - Previous research shows that leanness- and weight-dependent sports increase the
      risk of developing disturbed eating behaviour. This study investigated whether
      adolescent aesthetic athletes (n=68, M=14.6 years), particularly ballet dancers
      and figure skaters, exhibit more eating pathology compared to the general
      population. Furthermore, it was investigated whether sport-related factors have
      explanatory value for the dieting behaviour of aesthetic athletes. To asses
      eating pathology, reliable and valid self-report questionnaires were used
      including the Eating Disorder Inventory-II, the Children's Eating Disorder
      Examination-Questionnaire and the Dutch Eating Behaviour Questionnaire. Results
      show that female aesthetic athletes show more drive for thinness, features of
      bulimia, dieting behaviour and concerns about weight and shape compared to female
      adolescents from the general population. Concerning the explanation of dieting
      behaviour in aesthetic athletes, both sport-related factors (competition state
      anxiety) and general risk factors (eating concern) seem to be relevant. These
      results suggest that female aesthetic athletes show more disturbed eating
      behaviour and thoughts than female adolescents from the general population and
      therefore may have an enhanced risk of developing clinical eating disorders.

PMID- 22365794
TI  - The validity of the transdiagnostic cognitive behavioural model of eating
      disorders in predicting dietary restraint.
AB  - The study examined the validity of the transdiagnostic cognitive behavioural
      theory of eating disorders. The aim was to determine if the maintaining
      mechanisms of clinical perfectionism, core low self esteem, mood intolerance and
      interpersonal difficulties have a direct impact on dietary restraint or an
      indirect impact via eating, shape and weight concerns. The model was tested in a
      community sample of 224 females recruited via the internet. The structural
      equation model provided a good fit for the data. The relationship between
      maintaining mechanisms and dietary restraint was due to maintaining mechanisms
      impacting indirectly on dietary restraint via eating disorder psychopathology.
      The results lend support for the validity of the transdiagnostic model of eating
      disorders as the maintaining mechanisms lead to restraint via the core
      psychopathology of eating concerns, weight concerns and shape concerns. The
      findings suggest the four maintaining mechanisms alone are not enough to lead to
      dietary restraint, the core psychopathology of eating disorders needs to be
      present, which supports the predictions of the theory. These results help
      establish the validity of the transdiagnostic cognitive behavioural theory of
      eating disorders.

PMID- 22365795
TI  - Exercising for weight and shape reasons vs. health control reasons: the impact on
      eating disturbance and psychological functioning.
AB  - The aim of this study was to determine the prevalence and correlates of exercise
      motivated by health and weight/shape reasons. In total, 301 participants (53.5%
      males) completed questionnaires assessing eating behaviors, affect, self-esteem
      and attitudes toward exercise. Almost 48% of the participants reported that their
      exercise is motivated by weight/shape reasons. These individuals were more likely
      to report eating problems and more positive affect after exercising. For both
      groups, gender, ideal weight, and the impact of weight gain on self-esteem
      significantly predict disordered eating. Body mass index, affect, and attitudes
      toward exercise also emerged as predictors for the health reasons group. Weight
      and shape control reasons for exercise participation were very common and related
      to eating disturbance.

PMID- 22365796
TI  - Quality of life and motivation to change in eating disorders. Perception patient
      psychiatrist.
AB  - PURPOSE: To assess motivation to change (Mch) of patients with an eating disorder
      (ED) and its relationship with quality-of-life (QoL) by comparing patient and
      psychiatrist perceptions. METHOD: Patients (n=358) with an ED completed the
      disease-specific Health-Related Quality of Life for Eating Disorders (HeRQoLED)
      questionnaire, the Eating Attitudes Test (EAT-26) and the Short-Form Health
      Survey (SF-12) at baseline; 273 completed them after 1 year of treatment. The
      relationship between health-related quality of life (HRQoL) and the Mch stage was
      assessed using analysis of variance. Chi-square and Kappa statistical analysis
      assessed congruence in motivational change perception of the patients and
      psychiatrists. RESULTS: Higher patient-reported Mch was associated with higher
      HRQoL at the study beginning and end but not using the patient Mch as perceived
      by the psychiatrist. Initially, the patient and psychiatrist perceptions of Mch
      differed (kappa coefficient, -0.01); after 1 year they tended to converge
      (k=0.34). CONCLUSIONS: Higher Mch and higher QoL are positively associated.
      However, patient and psychiatrist perceptions of Mch and the relationship with
      QoL differ. After 1 year of treatment, these differences decreased.

PMID- 22365797
TI  - Disordered eating and complexities of cultural origin: a focus on Jews from
      Muslim countries.
AB  - CONTEXT: A dearth of data concerning eating problems among adult women from
      diverse cultural origins leaves substantial knowledge gaps and constrains
      evidence-based interventions. OBJECTIVE: To examine prevalence and predictors of
      disordered eating behaviors (DEB) among adult Jewish women (21+) from distinct
      cultural origins. DESIGN: Community-based study includes 175 Israelis born to
      parents from Muslim countries (aka Sephardic) and 108 second generation Israelis
      mostly of European ancestry. DEB assessed with DSM-IV related symptoms.
      Hierarchical regressions examine influence of weight, self-criticism and
      psychological distress on DEB severity. RESULTS: Despite similar exposure to
      Israel's westernized norms, substantial group differences emerge. Considerably
      lower rate of DEB found among respondents of Sephardic origin (11.4%, 19.4%,
      p<.05); regressions reveal dissimilar patterns of clinical predictors.
      CONCLUSIONS: Community cohesiveness and deeply-rooted cultural and religious
      traditions may be protective for Israelis of Sephardic origin. Additional
      research is needed to clarify cultural influences and enhance culturally
      sensitive interventions for multicultural populations.

PMID- 22365798
TI  - Do exercise motives predict obligatory exercise?
AB  - Few studies have examined whether factors predicting obligatory exercise differ
      by gender. 303 participants completed the Obligatory Exercise Questionnaire and
      the Reason for Exercise Inventory. All variables correlated significantly.
      However, the correlation between exercising for fitness and obligatory exercise
      was significantly stronger in women than men. In women, obligatory exercise was
      predicted by exercising to improve body tone, fitness, and to enhance mood; in
      men, obligatory exercise was predicted by exercising to improve body tone,
      enjoyment, and perceived attractiveness. Implications for treatment are
      discussed.

PMID- 22365799
TI  - Thinness expectations and weight cycling in a sample of middle-aged adults.
AB  - BACKGROUND: The False Hope Syndrome suggests that unrealistic expectations of
      dieting and weight loss are key constructs in the prediction of behavioral
      failure and may exacerbate weight cycling. The objective of this study was to
      determine cross-sectional associations among dieting and thinness expectations
      and weight cycling history within the framework of the False Hope Syndrome.
      METHODS: Participants were middle-aged (45+/-12 years) women (n=116) and men
      (n=98) recruited via worksite intranet distributions. Information on dieting and
      thinness expectations, weight loss attempts, and weight cycling history was
      gathered using standard questionnaires. RESULTS: More women than men reported
      currently dieting (43% vs. 26%; p<0.01). Moderate [OR=2.54; 95%CI: 1.01-6.45] and
      higher [OR=2.70; 95%CI: 1.07-6.80] levels of the thinness expectation score were
      significantly associated with the greater odds of weight cycling, independent of
      age, sex, BMI, and weight loss attempts. CONCLUSIONS: These data are the first to
      extend the pervasive and potent influence of thinness expectancy to middle-aged
      persons and in particular, to men.

PMID- 22365800
TI  - Who benefits most from guided self-help for binge eating? An investigation into
      the clinical features of completers and non-completers.
AB  - Guided self-help (GSH) is a recommended first step in treatment for bulimia
      nervosa (BN) and binge eating disorder (BED) (NICE, 2004). It remains unclear
      what makes some individuals more likely to respond to this form of treatment than
      others. Forty-eight patients participated in this study using a GSH programme for
      binge eating. Profiles of treatment completers and non-completers are compared,
      and reasons for non-completion explored. Completion of treatment was associated
      with significant improvements in mood, general functioning and on measures of
      dietary restraint, frequency of objective binge eating (OBE), laxative misuse,
      self-induced vomiting (SIV) and driven exercise. Improvements were maintained at
      follow-up. Treatment non-completers reported significantly higher pre-treatment
      levels of depression and weight concern, and lower levels of general health and
      vitality. Reasons for discontinuing treatment were related to perceptions of the
      GSH programme; practicalities of the programme; and readiness to change. Whilst
      GSH can be effective for a sub-group of patients, factors such as pre-morbid
      level of depression, degree of weight concern, perceptions of the programme, and
      readiness to change may increase the likelihood of non-completion.

PMID- 22365801
TI  - Do parental feeding practices moderate the relationships between impulsivity and
      eating in children?
AB  - This study examines the relationships between children's impulsivity, their
      eating behaviours, and their perceptions of their parent's feeding practices. 153
      10-13 year old children completed questionnaires assessing their eating
      behaviours, their impulsiveness and their perception of their parent's feeding
      practices. Children's reports of dysfunctional eating behaviours were
      significantly correlated with their perceptions of their parents feeding
      practices and with their levels of impulsivity. Children's reports of parental
      monitoring of their food intake significantly moderated the influence of child
      impulsiveness upon emotional eating. Children's perceptions of parental
      monitoring of their food intake may potentially have a protective effect at
      preventing more impulsive children from eating in response to emotional feelings.

PMID- 22365802
TI  - Effects of low dose tryptophan depletion on emotional processing in dieters.
AB  - Biased processing of ED-relevant stimuli (eg Fairburn, Shafran, & Cooper, 1999)
      and 5-HT function (Kaye, Fudge, & Paulus, 2009) are implicated in vulnerability
      to and the maintenance of eating disorders (EDs), but it is not known if these
      findings are connected: Could manipulating 5-HT function affect the processing of
      ED-relevant stimuli? To address this question we assessed emotional processing in
      female dieters (T+n=12, T-n=14) following acute low dose tryptophan depletion.
      ATD increased interference in the masked condition of the emotional Stroop to all
      negative emotional stimuli, in the absence of any other differences in emotional
      processing. These results suggest that ATD affects the processing of some
      negative (including ED-relevant) stimuli, and that reduced 5-HT function may be
      involved in some aspects of psychological vulnerability to EDs.

PMID- 22365803
TI  - The impact of age and BMI on Eating Disorder Examination Questionnaire (EDE-Q)
      scores in a community sample.
AB  - OBJECTIVES: The primary objectives for this study were to establish normative
      data for the EDE-Q in a nationally representative sample of women and to
      investigate the unique and relative effects of age and BMI. METHODS: A community
      sample of 3000 women aged 16-50 was randomly selected from the Norwegian National
      Population Register. RESULTS: Mean global EDE-Q was 1.27 (SD=1.19). EDE-Q scores
      decreased significantly with age yet increased with BMI. In the regression model,
      BMI and age accounted for 19% versus 2%, respectively, of the global EDE-Q.
      Extreme shape and weight concerns appeared to drive the higher global EDE-Q
      scores for individuals with overweight or obesity, with 30-40% scoring above the
      recommended clinical cut-off for Shape and Weight Concern. CONCLUSIONS: Higher
      EDE-Q scores, largely driven by elevated shape and weight concerns, appear
      normative among individuals with obesity in a nationally representative
      population. BMI should be routinely considered when establishing criteria for
      defining recovery and determining clinical significance using the EDE-Q.

PMID- 22365804
TI  - Associations between eating patterns, dietary intakes and eating behaviors in
      premenopausal overweight women.
AB  - The regulation of energy intake is complex and many biological, psychosocial and
      environmental influences have been identified. To our knowledge, no study has yet
      investigated how eating patterns could mediate associations between eating
      behaviors and self-reported energy intake in premenopausal overweight women.
      Therefore, objectives of this study were to examine associations between eating
      behaviors and eating patterns in premenopausal overweight women and to test if
      eating patterns could mediate the associations between eating behaviors and self
      reported energy intake. Women completed a 3-day food record and the Three-Factor
      Eating Questionnaire was used to assess eating behaviors (dietary restraint,
      disinhibition, hunger). In the total sample of women, flexible restraint was
      negatively (r=-0.18; p=0.03) and binge eating severity was positively (r=0.24;
      p=0.004) associated with self-reported energy intake. Moreover, flexible
      restraint was positively associated with the proportion of energy intake at
      breakfast (r=0.24; p=0.004), whereas disinhibition and binge eating severity were
      positively associated with the proportion of energy intake from snacks consumed
      after 5:00 pm (r=0.22, p=0.007 and r=0.22, p=0.01, respectively). In addition,
      mediational analyses showed that proportion of energy intake from snacks consumed
      after 5:00 pm explained 24.1% of the association between binge eating severity
      and self-reported energy intake. In conclusion, these results suggest that eating
      patterns are important factors to consider in order to explain the associations
      between eating behaviors and self-reported energy intake.

PMID- 22365805
TI  - The relationship between anxiety sensitivity and disordered eating: the mediating
      role of experiential avoidance.
AB  - This study examined the role of experiential avoidance in the association between
      dimensions of anxiety sensitivity (AS) and disordered eating. A sample of 395
      undergraduate students completed a series of questionnaires assessing the
      constructs of interest. Results indicate that the AS dimension of fear of
      cognitive dyscontrol was significantly uniquely associated with disordered
      eating. Furthermore, results provide support for a model in which experiential
      avoidance mediates the association between fear of cognitive dyscontrol and
      disordered eating. Findings of the present study highlight one potential
      mechanism underlying the association between AS and disordered eating, suggesting
      that efforts to avoid internal experiences may play a role in eating pathology.
      Clinical implications of these findings are discussed.

PMID- 22365806
TI  - What if high expectations feel good? Perceived parental expectations, their
      meanings, and bulimic symptoms in Black and White college women.
AB  - This study aimed to test an interactive model of perceived parental expectations
      and the meaning of those expectations in relation to bulimic symptoms in Black
      (n=97) and White (n=179) college women. Black young women reported higher
      parental expectations and attached more positive meanings to high parental
      expectations, in comparison to their White peers. There was an interactive effect
      for Black young women such that, in the context of perceived high parental
      expectations, interpreting high parental expectations as negative was associated
      with higher levels of bulimic symptoms whereas interpreting high expectations as
      positive was associated with lower levels of bulimic symptoms. However, no
      interactive effect emerged for White young women. The role of differences in
      cultural contexts is discussed.

PMID- 22365807
TI  - Loss of control eating in African-American and Caucasian youth.
AB  - Loss of control (LOC) eating, a disinhibited eating behavior shown to predict
      excessive weight gain in youth, has been reported by African-American children
      and adolescents. Yet, little is known about how LOC-eating manifests in this
      population. To investigate potential racial differences in LOC-eating, the Eating
      Disorder Examination was administered to 185 non-Hispanic African-American and
      Caucasian youth ages 8-17 y. Objective eating was assessed at two test meals
      during which youth ate ad libitum from a multi-item lunchtime food array. African
      American and Caucasian youth reported a similar prevalence of LOC episodes (24.2%
      vs. 28.9%, p=.75). Yet, accounting for sex, age, fat-free mass, percent fat mass,
      height, and socioeconomic status, African-Americans consumed more total energy at
      both laboratory meals (1608+/-57 kcal vs. 1362+/-44 kcal; p<.001). Furthermore,
      African-American youth reporting LOC consumed the most total energy across both
      meals (1855+/-104 kcal) compared to African-Americans without LOC (1524+/-60
      kcal), Caucasians with LOC (1278+/-68 kcal), and Caucasians without LOC (1399+/
      46 kcal; p<.001). Future research is required to examine whether LOC-eating
      contributes to the high rates of obesity in African-American youth.

PMID- 22365808
TI  - Relationship of fruit, vegetable, and fat consumption to binge eating symptoms in
      African American and Hispanic or Latina women.
AB  - African American (AA) and Hispanic or Latina (HL) women have the highest rates of
      overweight and obesity of any gender and ethnic groups. Binge eating disorder
      (BED) is the most common eating disorder in the United States and is linked to
      overweight and obesity. Traditional treatments for BED may not be appropriate or
      viable for AA and HL women, because they are less likely than whites to seek
      treatment for psychological conditions and may have less access to healthcare.
      Improving dietary habits in those with BED or subthreshold BED may reduce binge
      eating symptoms. The current study investigated the association of fruit,
      vegetable, and fat consumption to binge eating symptoms in AA and HL women. AA
      and HL women in the Health Is Power (HIP) study (N=283) reported fruit and
      vegetable intake, fat intake, and binge eating symptoms. Women were middle aged
      (M=45.8 years, SD=9.2) and obese (M BMI=34.5 kg/m(2), SD=7.5). Greater fat
      consumption was correlated with lower fruit and vegetable consumption (r(s)=
      0.159, p<0.01). Higher BMI (r(s)=0.209, p<0.01), and greater fat consumption
      (r(s)=0.227, p<0.05) were correlated with increased binge eating symptoms.
      Multiple regression analysis demonstrated that for HL women (beta=0.130,
      p=0.024), higher BMI (beta=0.148, p=0.012), and greater fat consumption
      (beta=0.196, p=0.001) were associated with increased binge eating symptoms
      (R(2)=0.086, F(3,278)=8.715, p<0.001). Findings suggest there may be a
      relationship between fat consumption and binge eating symptoms, warranting
      further study to determine whether improving dietary habits may serve as a
      treatment for BED in AA and HL women.

PMID- 22365809
TI  - Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene
      delivery.
AB  - A low molecular weight polyethyleneimine (PEI 1.8 kDa) was modified with
      dioleoylphosphatidylethanolamine (PE) to form the PEI-PE conjugate investigated
      as a transfection vector. The optimized PEI-PE/pDNA complexes at an N/P ratio of
      16 had a particle size of 225 nm, a surface charge of +31 mV, and protected the
      pDNA from the action of DNase I. The PEI-PE conjugate had a critical micelle
      concentration (CMC) of about 34 MUg/ml and exhibited no toxicity compared to a
      high molecular weight PEI (PEI 25 kDa) as tested with B16-F10 melanoma cells. The
      B16-F10 cells transfected with PEI-PE/pEGFP complexes showed protein expression
      levels higher than with PEI-1.8 or PEI-25 vectors. Complexes prepared with YOYO 1
      labeled pEGFP confirmed the enhanced delivery of the plasmid with PEI-PE compared
      to PEI-1.8 and PEI-25. The PEI-PE/pDNA complexes were also mixed with various
      amounts of micelle-forming material, polyethylene glycol (PEG)-PE to improve
      biocompatibility. The resulting particles exhibited a neutral surface charge,
      resistance to salt-induced aggregation, and good transfection activity in the
      presence of serum in complete media. The use of the low-pH-degradable PEG
      hydrazone-PE produced particles with transfection activity sensitive to changes
      in pH consistent with the relatively acidic tumor environment.

PMID- 22365810
TI  - The targeted intracellular delivery of cytochrome C protein to tumors using lipid
      apolipoprotein nanoparticles.
AB  - Intracellular-acting therapeutic proteins offer a promising clinical alternative
      to extracellular-acting agents, but are limited in efficacy by their low
      permeability into the cell cytoplasm. We have developed a nanoparticle (NP)
      composed of lipid (DOTAP/DOPE) and apolipoprotein (APOA-I) to mediate the
      targeted delivery of intracellular-acting protein drugs to non-small cell lung
      tumors. NPs were produced with either GFP, a fluorescent model protein, or
      cytochrome C (cytC), an inducer of apoptosis in cancer cells. GFP and cytC were
      separately conjugated with a membrane permeable sequence (MPS) peptide and were
      admixed with DOPE/DOTAP nanoparticle formulations to enable successful protein
      loading. Protein-loaded NPs were modified with DSPE-PEG-Anisamide to enable
      specific NP targeting to the tumor site in a xenograft model. The resulting
      particle was 20-30 nm in size and exhibited a 64-75% loading efficiency. H460
      cells treated with the PEGylated MPS-cytC-NPs exhibited massive apoptosis. When
      MPS-GFP-NPs or MPS-cytC-NPs were intravenously administered in H460 tumor bearing
      mice, a specific tumor targeting effect with low NP accumulation in the liver was
      observed. In addition, MPS-cytC-NP treatment provoked a tumor growth retardation
      effect in H460 xenograft mice. We conclude that our NP enables targeted,
      efficacious therapeutic protein delivery for the treatment of lung cancer.

PMID- 22365811
TI  - Microfabrication of complex porous tissue engineering scaffolds using 3D
      projection stereolithography.
AB  - The success of tissue engineering will rely on the ability to generate complex,
      cell seeded three-dimensional (3D) structures. Therefore, methods that can be
      used to precisely engineer the architecture and topography of scaffolding
      materials will represent a critical aspect of functional tissue engineering.
      Previous approaches for 3D scaffold fabrication based on top-down and process
      driven methods are often not adequate to produce complex structures due to the
      lack of control on scaffold architecture, porosity, and cellular interactions.
      The proposed projection stereolithography (PSL) platform can be used to design
      intricate 3D tissue scaffolds that can be engineered to mimic the
      microarchitecture of tissues, based on computer aided design (CAD). The PSL
      system was developed, programmed and optimized to fabricate 3D scaffolds using
      gelatin methacrylate (GelMA). Variation of the structure and prepolymer
      concentration enabled tailoring the mechanical properties of the scaffolds. A
      dynamic cell seeding method was utilized to improve the coverage of the scaffold
      throughout its thickness. The results demonstrated that the interconnectivity of
      pores allowed for uniform human umbilical vein endothelial cells (HUVECs)
      distribution and proliferation in the scaffolds, leading to high cell density and
      confluency at the end of the culture period. Moreover, immunohistochemistry
      results showed that cells seeded on the scaffold maintained their endothelial
      phenotype, demonstrating the biological functionality of the microfabricated
      GelMA scaffolds.

PMID- 22365812
TI  - Enrichment of cell populations in metaphase, anaphase, and telophase by
      synchronization using nocodazole and blebbistatin: a novel method suitable for
      examining dynamic changes in proteins during mitotic progression.
AB  - Mitosis is a continuous process to separate replicated chromosomes into two
      daughter cells through prophase, metaphase, anaphase, and telophase. Although a
      number of methods have been established to synchronize cells at different phases
      of the cell cycle, it is difficult to synchronize cells at the specific phases,
      anaphase and telophase, during mitosis because of the short duration of anaphase.
      Here, we show that HeLa S3 cells in anaphase and in telophase are successfully
      enriched by treatment with a combination of low concentrations of the microtubule
      depolymerizing agent nocodazole and the myosin II inhibitor blebbistatin. After 9
      h release from thymidine block at G1/S phase, addition of nocodazole at 20 ng/ml
      but not 40 ng/ml ensures rapid release from the nocodazole arrest. Subsequently,
      the cells are cultured in the presence of 50 MUM blebbistatin for 20 and 50 min
      to enrich cells in anaphase and telophase, respectively. Western blot analysis
      verifies down-regulation of phospho-histone H3-Ser10, phospho-Aurora A/B/C, and
      cyclin B1 during M-phase progression. Furthermore, we show how the
      electrophoretic mobility shifts of the Src-family kinases c-Yes and c-Src can
      change in each phase of mitosis. These results provide a useful synchronization
      method for biochemically examining protein dynamics during M-phase progression.

PMID- 22365813
TI  - Young dentate granule cells mediate pattern separation, whereas old granule cells
      facilitate pattern completion.
AB  - Adult-born granule cells (GCs), a minor population of cells in the hippocampal
      dentate gyrus, are highly active during the first few weeks after functional
      integration into the neuronal network, distinguishing them from less active,
      older adult-born GCs and the major population of dentate GCs generated
      developmentally. To ascertain whether young and old GCs perform distinct memory
      functions, we created a transgenic mouse in which output of old GCs was
      specifically inhibited while leaving a substantial portion of young GCs intact.
      These mice exhibited enhanced or normal pattern separation between similar
      contexts, which was reduced following ablation of young GCs. Furthermore, these
      mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern
      separation requires adult-born young GCs but not old GCs, and older GCs
      contribute to the rapid recall by pattern completion. Our data suggest that as
      adult-born GCs age, their function switches from pattern separation to rapid
      pattern completion.

PMID- 22365815
TI  - [Profitability of a day hospital: analysis of activity, cost and effectiveness].
AB  - OBJECTIVE: Day hospitals are an alternative to conventional hospital care. We
      analyzed the functioning and profitability of the day hospital of Hospital
      Clinico de Valladolid, Spain, in 2009. Profitability is expressed as the
      provision of identical health coverage at a lower cost than that generated by
      conventional hospital care and with adequate quality indicators. METHODS: We
      performed a retrospective, observational and descriptive study of the information
      obtained on each patient attended in the day hospital from January 1 to December
      31, 2009. We studied four quality indicators: cancellation of meetings, the rate
      of transfusion reactions, the out-patient rate and the satisfaction index. The
      estimated savings for each process was calculated as the difference in the
      average cost of hospitalization minus the average cost of the process in the day
      hospital. RESULTS: The most frequent diseases were systemic and connective tissue
      diseases, accounting for 25.4% of the processes treated; of these, 17.1%
      corresponded to rheumatoid arthritis. Patient satisfaction was 93%. Meetings
      cancellations and the rate of transfusion reactions were 0%. The out-patient rate
      was 26%. Day hospital costs were 8.6% of conventional hospital costs, with
      savings of 78,390.69 euros. CONCLUSION: The day hospital is cost effective due to
      savings compared with conventional hospitalization and has a satisfactory quality
      index.

PMID- 22365814
TI  - Mutually exclusive binding of telomerase RNA and DNA by Ku alters telomerase
      recruitment model.
AB  - In Saccharomyces cerevisiae, the Ku heterodimer contributes to telomere
      maintenance as a component of telomeric chromatin and as an accessory subunit of
      telomerase. How Ku binding to double-stranded DNA (dsDNA) and to telomerase RNA
      (TLC1) promotes Ku's telomeric functions is incompletely understood. We
      demonstrate that deletions designed to constrict the DNA-binding ring of Ku80
      disrupt nonhomologous end-joining (NHEJ), telomeric gene silencing, and telomere
      length maintenance, suggesting that these functions require Ku's DNA end-binding
      activity. Contrary to the current model, a mutant Ku with low affinity for dsDNA
      also loses affinity for TLC1 both in vitro and in vivo. Competition experiments
      reveal that wild-type Ku binds dsDNA and TLC1 mutually exclusively. Cells
      expressing the mutant Ku are deficient in nuclear accumulation of TLC1, as
      expected from the RNA-binding defect. These findings force reconsideration of the
      mechanisms by which Ku assists in recruiting telomerase to natural telomeres and
      broken chromosome ends. PAPERCLIP:

PMID- 22365816
TI  - [Questionnaire to assess behavior, knowledge and attitudes on hand hygiene among
      physicians].
AB  - OBJECTIVE: Valid and reliable instruments to measure aspects of hand hygiene are
      needed to determine the current situation and impact of training among health
      professionals. The main objective of this study was to describe the development
      of a questionnaire on hand hygiene among health professionals and to analyze the
      properties of this instrument. METHOD: A questionnaire was designed and
      implemented between January 2010 and March 2011 at the Hospital Clinico San
      Cecilio (Granada, Spain). The final questionnaire consisted of 44 items that
      assessed provider behavior before and after contact with the patient, declarative
      knowledge, and attitudes to hand hygiene. The questionnaire was administered to
      113 health professionals. RESULTS: A factor analysis was performed. Data were
      obtained that supported the unidimensionality of the instrument with a general
      convergence value that explained 39.289% of the total variance and a Cronbach's
      alpha of 0.784 for the established elements. Significant differences were found
      in hand hygiene behavior before and after contact with the patient (t=-8,991, p
      <0.001). Declarative knowledge and attitudes significantly predicted behavior.
      CONCLUSIONS: The questionnaire shows high internal consistency, reliability, and
      validity and is thus a valid tool to assess behavior, knowledge and attitudes
      related to hand hygiene in health professionals. This instrument also detects
      deficiencies in basic knowledge.

PMID- 22365817
TI  - Patient reported activities after reverse shoulder arthroplasty: part II.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) is becoming a commonly performed
      procedure. Surgeons are advised to select older patients with lower demands. This
      study defines patient reported activities following RSA. MATERIALS AND METHODS:
      Seventy-eight patients with 81 treated shoulders (average age 73 years; 49 women,
      32 men) completed a survey asking about clinical parameters: pain, motion,
      strength, and 72 different activities. Diagnoses were rotator cuff tear
      arthropathy in 70 shoulders, massive rotator cuff tears with psuedoparalysis in
      6, and failed treatment for proximal humeral fractures in 5. Average time from
      surgery to survey was 3.6 years (range, 3-5). RESULTS: All clinical parameters
      were favorable. The 3 most commonly reported activities were low demand (cooking,
      baking, and driving), medium demand (gardening, leaf raking, and lawn mowing),
      and high demand (snow shoveling, wheelbarrow use, and dirt shoveling). These were
      comparable to the activities reported for total shoulder arthroplasty and
      hemiarthroplasty. There was no clinical or activity difference between those
      components with a lateral or a medial center of rotation. CONCLUSION: A
      significant proportion of patients continue medium or high demand activities
      following RSA. These are similar to other types of shoulder arthroplasties.
      Future studies to determine the safety level of different activities would be
      helpful to counsel patients accordingly.

PMID- 22365818
TI  - Do the indications, results, and complications of reverse shoulder arthroplasty
      change with surgeon's experience?
AB  - BACKGROUND: The goal of this study was to compare 2 consecutive series of 240
      reverse total shoulder arthroplasties (TSA) in order to evaluate if the increase
      in surgeon experience modified the indications, clinical and radiographic
      results, and rate of complications. MATERIAL AND METHODS: Two hundred forty
      reverse TSA performed between July 2003 and March 2007 were clinically and
      radiographically evaluated by an independent examiner with a minimum follow-up of
      2 years and compared with a previous published study (240 cases implanted by the
      same 2 surgeons between May 1995 and June 2003). RESULTS: The main etiology
      remained cuff tear arthropathy with an increase noted between the 2 studies. The
      rate of revision arthroplasty as an etiology decreased from 22.5% to 9.1%.
      Conversely, the rate of rheumatoid arthritis increased from 0.4% to 6.3%. The
      average postoperative Constant score was significantly better than the first
      series (66.9 vs 59.7, P < .001). The postoperative complication rate decreased
      with increased experience (from 19% to 10.8%), with dislocations reducing (from
      7% to 3.2%), and infections reducing (from 4% to 0.9%). However, the number of
      nerve palsies increased. The revision rate decreased from 7.5% to 5%. The rate of
      glenoid notching remained stable, but the severity of notching decreased.
      CONCLUSION: Experience did not lead us to operate on younger patients, but
      significantly modified patient selection, results, and complications. Increased
      experience with the reverse shoulder arthroplasty did not reduce the rate of
      glenoid notching.

PMID- 22365819
TI  - Irreducible luxatio erecta humeri caused by an aberrant position of the axillary
      nerve.

PMID- 22365820
TI  - Oxytocin increases amygdala reactivity to threatening scenes in females.
AB  - The neuropeptide oxytocin (OT) is well known for its profound effects on social
      behavior, which appear to be mediated by an OT-dependent modulation of amygdala
      activity in the context of social stimuli. In humans, OT decreases amygdala
      reactivity to threatening faces in males, but enhances amygdala reactivity to
      similar faces in females, suggesting sex-specific differences in OT-dependent
      threat-processing. To further explore whether OT generally enhances amygdala
      dependent threat-processing in females, we used functional magnetic resonance
      imaging (fMRI) in a randomized within-subject crossover design to measure
      amygdala activity in response to threatening and non-threatening scenes in 14
      females following intranasal administration of OT or placebo. Participants' eye
      movements were recorded to investigate whether an OT-dependent modulation of
      amygdala activity is accompanied by enhanced exploration of salient scene
      features. Although OT had no effect on participants' gazing behavior, it
      increased amygdala reactivity to scenes depicting social and non-social threat.
      In females, OT may, thus, enhance the detection of threatening stimuli in the
      environment, potentially by interacting with gonadal steroids, such as
      progesterone and estrogen.

PMID- 22365821
TI  - Pyoderma gangrenosum.

PMID- 22365822
TI  - Radiocapitellar cartilage injuries associated with tennis elbow syndrome.
AB  - PURPOSE: A recent anatomical study has suggested that considerable contact
      between the undersurface of the extensor carpi radialis brevis (ECRB) and the
      lateral edge of the capitellum is the cause of tendon injury in lateral
      epicondylosis. We hypothesized that this contact might concurrently induce
      cartilage injuries of the capitellum. The purpose of the present study was to
      determine the prevalence, location, and severity of cartilage lesions of the
      radiocapitellar joint accompanying lateral epicondylosis and to identify their
      correlation with ECRB status. METHODS: Arthroscopic assessment of the articular
      cartilage was performed for 31 elbows in 31 patients with lateral epicondylosis
      who had surgery. The study group consisted of 18 women and 13 men with a mean age
      of 50 years (range, 35 to 67 y). The relationship between the presence of the
      cartilage lesions and patient demographics, preoperative pain visual analog scale
      score, number of cortisone injections, and surgical findings including ECRB tears
      were investigated. RESULTS: Cartilage injuries of the capitellum were found in 20
      (65%) and cartilage injuries of the radial head were found in 25 (81%) of 31
      elbows. Most of the lesions were located on the lateral aspect of the capitellum
      and radial head. Multivariate logistic regression analysis revealed that the
      absence of ECRB tears was independently associated with a higher risk of
      cartilage injuries of the capitellum. CONCLUSIONS: Cartilage injury was
      frequently found in the lateral edge of the capitellum and radial head. Lesions
      of the capitellum were related to the absence of ECRB tears. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Prognostic IV.

PMID- 22365823
TI  - Radial nerve injury during double plating of a displaced intercondylar fracture.
AB  - Double-plate fixation is a popular treatment method for intercondylar humeral
      fractures. Ulnar nerve complications are emphasized, but radial nerve
      complications are rarely mentioned. We present a case of iatrogenic radial nerve
      palsy following open reduction and double plating of a
      supracondylar/intercondylar fracture of the humerus. Before surgery, only a
      sensory deficit in the radial nerve territory was present, but after surgery,
      there was a complete motor deficit of the wrist and finger extensors. On
      exploration, a segment of nerve was found crushed within the reduced lateral
      condyle fracture site, with a screw from the posteroradial plate going through
      the nerve. Although rare, radial nerve injury can occur with posteriorly
      displaced supracondylar/intercondylar humerus fractures. When preoperative signs
      of radial nerve injury are present, we recommend that the radial nerve be
      identified and protected during double-plate fixation.

PMID- 22365824
TI  - The mediator couples transcription and splicing.
AB  - Transcription is coupled with pre-mRNA splicing in metazoans. In the current
      issue of Molecular Cell, Huang et al. (2012) show that Med23 interacts with the
      RNA binding protein hnRNP L to regulate alternative splicing, thus expanding
      Mediator's function beyond transcriptional control.

PMID- 22365825
TI  - An RNA reset button.
AB  - In this issue of Molecular Cell, single-cell analyses by Bumgarner et al. (2012)
      reveal how two antagonistic long noncoding RNAs at the FLO11 locus define a
      toggle responsible for morphological heterogeneity in genetically identical
      populations of budding yeast.

PMID- 22365826
TI  - When noisy neighbors are a blessing: analysis of gene expression noise identifies
      coregulated genes.
AB  - In this issue of Molecular Cell, Stewart-Ornstein et al. (2012) use systematic
      pair-wise correlation analysis of expression noise in a large number of yeast
      genes to identify clusters of functionally related genes and signaling pathways
      responsible for elevated noise.

PMID- 22365827
TI  - Conservation between the RNA polymerase I, II, and III transcription initiation
      machineries.
AB  - Recent studies of the three eukaryotic transcription machineries revealed that
      all initiation complexes share a conserved core. This core consists of the RNA
      polymerase (I, II, or III), the TATA box-binding protein (TBP), and transcription
      factors TFIIB, TFIIE, and TFIIF (for Pol II) or proteins structurally and
      functionally related to parts of these factors (for Pol I and Pol III). The
      conserved core initiation complex stabilizes the open DNA promoter complex and
      directs initial RNA synthesis. The periphery of the core initiation complex is
      decorated by additional polymerase-specific factors that account for functional
      differences in promoter recognition and opening, and gene class-specific
      regulation. This review outlines the similarities and differences between these
      important molecular machines.

PMID- 22365828
TI  - Cellular noise regulons underlie fluctuations in Saccharomyces cerevisiae.
AB  - Stochasticity is a hallmark of cellular processes, and different classes of genes
      show large differences in their cell-to-cell variability (noise). To decipher the
      sources and consequences of this noise, we systematically measured pairwise
      correlations between large numbers of genes, including those with high
      variability. We find that there is substantial pathway variability shared across
      similarly regulated genes. This induces quantitative correlations in the
      expression of functionally related genes such as those involved in the Msn2/4
      stress response pathway, amino-acid biosynthesis, and mitochondrial maintenance.
      Bioinformatic analyses and genetic perturbations suggest that fluctuations in PKA
      and Tor signaling contribute to pathway-specific variability. Our results argue
      that a limited number of well-delineated "noise regulons" operate across a yeast
      cell and that such coordinated fluctuations enable a stochastic but coherent
      induction of functionally related genes. Finally, we show that pathway noise is a
      quantitative tool for exploring pathway features and regulatory relationships in
      un-stimulated systems.

PMID- 22365829
TI  - Epigenetic silencing of core histone genes by HERS in Drosophila.
AB  - Cell cycle-dependent expression of canonical histone proteins enables newly
      synthesized DNA to be integrated into chromatin in replicating cells. However,
      the molecular basis of cell cycle-dependency in the switching of histone gene
      regulation remains to be uncovered. Here, we report the identification and
      biochemical characterization of a molecular switcher, HERS (histone gene-specific
      epigenetic repressor in late S phase), for nucleosomal core histone gene
      inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent
      kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene
      regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin
      inactivation through histone H3 lysine 9 methylation. These findings illustrate a
      salient molecular switch linking epigenetic gene silencing to cell cycle
      dependent histone production.

PMID- 22365831
TI  - Conformational switching of the molecular chaperone Hsp90 via regulated
      phosphorylation.
AB  - Hsp90 is an essential molecular chaperone in the eukaryotic cytosol. Its function
      is modulated by cochaperones and posttranslational modifications. Importantly,
      the phosphatase Ppt1 is a dedicated regulator of the Hsp90 chaperone system.
      Little is known about Ppt1-dependent phosphorylation sites and how these affect
      Hsp90 activity. Here, we identified the major phosphorylation sites of yeast
      Hsp90 in its middle or the C-terminal domain and determined the subset regulated
      by Ppt1. In general, phosphorylation decelerates the Hsp90 machinery, reduces
      chaperone function in vivo, sensitizes yeast cells to Hsp90 inhibition and
      affects DNA repair processes. Modification of one particular site (S485) is
      lethal, whereas others modulate Hsp90 activity via distinct mechanisms affecting
      the ATPase activity, cochaperone binding and manipulating conformational
      transitions in Hsp90. Our mechanistic analysis reveals that phosphorylation of
      Hsp90 permits a regulation of the conformational cycle at distinct steps by
      targeting switch points for the communication of remote regions within Hsp90.

PMID- 22365830
TI  - Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double
      strand break signaling and repair.
AB  - DNA double-strand break (DSB) signaling and repair are critical for cell
      viability, and rely on highly coordinated pathways whose molecular organization
      is still incompletely understood. Here, we show that heterogeneous nuclear
      ribonucleoprotein U-like (hnRNPUL) proteins 1 and 2 play key roles in cellular
      responses to DSBs. We identify human hnRNPUL1 and -2 as binding partners for the
      DSB sensor complex MRE11-RAD50-NBS1 (MRN) and demonstrate that hnRNPUL1 and -2
      are recruited to DNA damage in an interdependent manner that requires MRN.
      Moreover, we show that hnRNPUL1 and -2 stimulate DNA-end resection and promote
      ATR-dependent signaling and DSB repair by homologous recombination, thereby
      contributing to cell survival upon exposure to DSB-inducing agents. Finally, we
      establish that hnRNPUL1 and -2 function downstream of MRN and CtBP-interacting
      protein (CtIP) to promote recruitment of the BLM helicase to DNA breaks.
      Collectively, these results provide insights into how mammalian cells respond to
      DSBs.

PMID- 22365832
TI  - Plk1-dependent phosphorylation of optineurin provides a negative feedback
      mechanism for mitotic progression.
AB  - Plk1 activation is required for progression through mitotic entry to cytokinesis.
      Here we show that at mitotic entry, Plk1 phosphorylates Optineurin (Optn) at
      serine 177 and that this dissociates Optn from the Golgi-localized GTPase Rab8,
      inducing its translocation into the nucleus. Mass spectrometry analysis revealed
      that Optn is associated with a myosin phosphatase complex (MP), which antagonizes
      the mitotic function of Plk1. Our data also indicate that Optn functionally
      connects this complex to Plk1 by promoting phosphorylation of the myosin
      phosphatase targeting subunit 1 (MYPT1). Accordingly, silencing Optn expression
      increases Plk1 activity and induces abscission failure and multinucleation, which
      were rescued upon expression of wild-type (WT) Optn, but not a phospho-deficient
      mutant (S177A) that cannot translocate into the nucleus during mitosis. Overall,
      these results highlight an important role of Optn in the spatial and temporal
      coordination of Plk1 activity.

PMID- 22365833
TI  - Dynamic protein-protein interaction wiring of the human spliceosome.
AB  - More than 200 proteins copurify with spliceosomes, the compositionally dynamic
      RNPs catalyzing pre-mRNA splicing. To better understand protein - protein
      interactions governing splicing, we systematically investigated interactions
      between human spliceosomal proteins. A comprehensive Y2H interaction matrix
      screen generated a protein interaction map comprising 632 interactions between
      196 proteins. Among these, 242 interactions were found between spliceosomal core
      proteins and largely validated by coimmunoprecipitation. To reveal dynamic
      changes in protein interactions, we integrated spliceosomal complex purification
      information with our interaction data and performed link clustering. These data,
      together with interaction competition experiments, suggest that during step 1 of
      splicing, hPRP8 interactions with SF3b proteins are replaced by hSLU7,
      positioning this second step factor close to the active site, and that the DEAH
      box helicases hPRP2 and hPRP16 cooperate through ordered interactions with GPKOW.
      Our data provide extensive information about the spliceosomal protein interaction
      network and its dynamics.

PMID- 22365834
TI  - Effect of an inactivated bluetongue serotype 8 vaccine on semen quality in rams.
AB  - The aim of this study was to determine whether a single dose of an inactivated
      bluetongue virus serotype 8 (BTV-8) vaccine altered semen quality in rams. Twenty
      sexually mature rams were assigned to three experimental groups: two groups of
      four animals were vaccinated and a third group of four animals was unvaccinated.
      The first group included rams with a history of natural BTV-8 infection in 2007
      and the second and third groups included BTV-8 naive rams. Semen was collected
      prior to vaccination and for 4 months post-vaccination. There were no significant
      differences in semen quality traits, including motility and concentration of
      spermatozoa, and percentages of living, normal dead and abnormal dead
      spermatozoa, between vaccinated and unvaccinated groups, or over time (P>0.05).
      The BTV-8 vaccine tested in this study did not appear to have any adverse effect
      on semen quality in rams.

PMID- 22365835
TI  - Information-hungry and disempowered: a qualitative study of women and their
      partners' experiences of severe postpartum haemorrhage.
AB  - OBJECTIVE: to explore how severe postpartum haemorrhage (PPH) and its management
      is experienced by women and their partners, and how they later view events.
      DESIGN: interpretive phenomenological qualitative study with semi-structured
      interviews. SETTING: in-depth interviews were conducted in participants' homes
      and focused on experiences of PPH in hospital and post-discharge. PARTICIPANTS:
      nine women who had experienced severe PPH and six partners. FINDINGS: this study
      demonstrates the stressful and emotional nature of severe PPH and extends the
      literature by considering partners' perspectives. Women and men had different
      experiences and information needs, but interviewees often shared a common desire
      for help to understand past events. A dominant theme of communication
      difficulties, and two subthemes, disempowerment and information-deprivation arose
      strongly from the data. Communication difficulties were understandable during the
      emergency but were frustrating and upsetting in postpartum care and the longer
      term. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: research is needed to develop
      better communication and supportive strategies, which might avoid the sense of
      disempowerment in this potentially vulnerable population. Different information
      and support needs for women and men should be considered whatever policies are
      implemented.

PMID- 22365837
TI  - Synthesis of heterocyclic N-(beta-D-glucopyranosyl)carboxamides for inhibition of
      glycogen phosphorylase.
AB  - In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylamine and
      propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylamine
      which was transformed by 1,3-dipolar cycloadditions with aromatic azides and
      nitrile-oxides to the corresponding O-peracetylated N-(beta-D-glucopyranosyl)-1
      substituted-1,2,3-triazole-4-carboxamides and N-(beta-D-glucopyranosyl)-3
      substituted-isoxazole-5-carboxamides, respectively. These compounds were O
      deacetylated by Zemplen's protocol to be tested as inhibitors of rabbit muscle
      glycogen phosphorylase b. The best inhibitors of the two series were N-(beta-D
      glucopyranosyl)-1-(3,5-dimethyl-phenyl)-1,2,3-triazole-4-carboxamide (K(i)=34
      MUM) and N-(beta-D-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide
      (K(i)=164 MUM).

PMID- 22365836
TI  - What does CNTNAP2 reveal about autism spectrum disorder?
AB  - Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous
      condition characterized by the presence of repetitive/restrictive behaviors and
      variable deficits in language and social behavior. Many genes predisposing an
      individual to ASD have been identified, and understanding the causal disease
      mechanism(s) is critical to be able to develop treatments. Neurobiological,
      genetic, and imaging data provide strong evidence for the CNTNAP2 gene as a risk
      factor for ASD and related neurodevelopmental disorders. This review discusses
      the clinical genetics and current understanding of the biology of CNTNAP2 as
      related to ASD and illustrates how the integration of multiple research
      approaches, from human studies to animal models, converge to inform functional
      biology focused on novel treatment development.

PMID- 22365838
TI  - Highly magnetizable superparamagnetic colloidal aggregates with narrowed size
      distribution from ferrofluid emulsion.
AB  - The formation of spherical superparamagnetic colloidal aggregates of magnetite
      nanoparticles by emulsification of a ferrofluid and subsequent solvent
      evaporation has been systematically studied. The colloidal aggregates occur as a
      dense sphere with magnetite nanoparticles randomly packed and preserved particle
      particle separation due to chemisorbed oleic acid. The voids between
      nanoparticles are filled with solvent and free oleic acid. The latter was found
      to influence the formation of colloidal aggregates and their surface properties.
      The choice of surfactant, whether low molecular weight or polymeric, was shown to
      lead to the colloidal aggregates having tailored interfacial behavior.
      Magnetization measurements at ambient temperature revealed that the magnetite
      colloidal aggregates preserve the superparamagnetic properties of the starting
      nanoparticle units and show high saturation magnetization values up to 57 emu/g.
      The size distribution of magnetite nanoparticle colloidal aggregates produced by
      such an approach was found to be a function of emulsion droplet breakup
      coalescence and stabilization kinetics and therefore is influenced by the
      emulsification process conditions and concentrations of the emulsion compounds.

PMID- 22365839
TI  - Monodisperse conducting colloidal dipoles with symmetric dimer structure for
      enhancing electrorheology properties.
AB  - This study introduces an electrorheological (ER) approach that allows us to
      obtain remarkably enhanced ER properties by using monodisperse colloidal dimer
      particles. Two sets of colloidal particles, which are spheres and symmetric
      dimers, were synthesized employing the seeded polymerization technique. The
      aspect ratio of dimer particles was ~1.43. Then, the surface of the particles was
      coated with polyaniline by using the chemically oxidative polymerization method.
      After preparation of the particle suspensions having the same particle volume and
      concentration, their ER behavior was investigated with changing the electric
      field strength. At the same experimental condition, both shear stress and shear
      yield stress of the dimer particle suspension remarkably increased, compared with
      those of the spherical particle suspension. This attributes to the fact that the
      shape anisotropy of suspending particles effectively led to increase in the
      dipole moment under the electric field, thus resulting in formation of a well
      structured colloidal chains between the electrodes.

PMID- 22365840
TI  - Opportunities and challenges of Web 2.0 for vaccination decisions.
AB  - A growing number of people use the Internet to obtain health information,
      including information about vaccines. Websites that allow and promote interaction
      among users are an increasingly popular source of health information. Users of
      such so-called Web 2.0 applications (e.g. social media), while still in the
      minority, represent a growing proportion of online communicators, including vocal
      and active anti-vaccination groups as well as public health communicators. In
      this paper, the authors: define Web 2.0 and examine how it may influence
      vaccination decisions; discuss how anti-vaccination movements use Web 2.0 as well
      as the challenges Web 2.0 holds for public health communicators; describe the
      types of information used in these different settings; introduce the theoretical
      background that can be used to design effective vaccination communication in a
      Web 2.0 environment; make recommendations for practice and pose open questions
      for future research. The authors conclude that, as a result of the Internet and
      Web 2.0, private and public concerns surrounding vaccinations have the potential
      to virally spread across the globe in a quick, efficient and vivid manner. Web
      2.0 may influence vaccination decisions by delivering information that alters the
      perceived personal risk of vaccine-preventable diseases or vaccination side
      effects. It appears useful for public health officials to put effort into
      increasing the effectiveness of existing communication by implementing
      interactive, customized communication. A key step to providing successful public
      health communication is to identify those who are particularly vulnerable to
      finding and using unreliable and misleading information. Thus, it appears
      worthwhile that public health websites strive to be easy to find, easy to use,
      attractive in its presentation and readily provide the information, support and
      advice that the searcher is looking for. This holds especially when less
      knowledgeable individuals are in need of reliable information about vaccination
      risks and benefits.

PMID- 22365841
TI  - Enhancement of protective immunity against intracellular bacteria using type-1
      polarized dendritic cell (DC) vaccine.
AB  - The development of effective vaccine strategies for intracellular bacteria,
      including tuberculosis, is one of the major frontiers of medical research. Our
      previous studies showed that dendritic cell (DC) vaccine is a promising approach
      for eliciting protective immunity against intracellular bacteria. However, it has
      been reported that standard fully mature DCs show reduced ability to produce IL
      12p70 upon subsequent interaction with antigen (Ag)-specific T cells, limiting
      their in vivo performance for vaccines. Recently, we found that such "DC
      exhaustion" could be prevented by the presence of IL-4 and IFN-gamma during the
      maturation of mouse DCs (type-1 polarization), resulting in improved induction of
      anti-tumor immunity in cancer. Here we show that such type-1 polarized DCs
      promote dramatic enhancement of protective immunity against an intracellular
      bacterium, Listeria monocytogenes. Murine bone marrow-derived DCs were cultured
      and matured with LPS, IL-4 and IFN-gamma (type-1 polarized DCs), and with LPS
      alone (non-polarized DCs). DCs were loaded with listeriolysin O (LLO) 91-99, H2
      K(d)-restricted epitope of L. monocytogenes, and were injected into naive BALB/c
      mice intravenously. Type-1 polarized DCs produced significantly higher levels of
      IL-12p70 than non-polarized DCs in vitro, and this vaccine strongly enhanced LLO
      91-99-specific CD8(+) T cells exhibiting epitope-specific cytotoxic activity and
      IFN-gamma production, leading to significant induction of protective immunity
      against L. monocytogenes. Type-1 polarized DCs are potential candidates for
      enhancing protective immunity in the design of effective vaccination strategies
      against intracellular bacteria.

PMID- 22365842
TI  - Nanomedicine and veterinary science: the reality and the practicality.
AB  - Nanomedicine is a rapidly expanding field with a promising future that is already
      permeating veterinary science. This review summarises the current applications
      for nanoparticles in human medicine and explores their potential applicability
      for veterinary use. The principles underlying the use of nanoparticles in drug
      delivery, imaging and as vaccine adjuvants are explored along with the unique
      issues surrounding nanoparticle toxicity and regulatory approval. A brief
      overview of the properties of different nanoparticle systems including,
      liposomes, micelles, emulsions and inorganic nanoparticles, is provided, along
      with a description of their current and potential future applications in
      veterinary medicine.

PMID- 22365843
TI  - Canine tissue-specific expression of multiple small leucine rich proteoglycans.
AB  - Small leucine rich proteoglycans (SLRPs) are important constituents of
      extracellular matrix (ECM) and contribute to the production, organization and
      remodelling of collagen and elastin through complex biological systems. The
      relative expression and distribution of SLRPs in a variety of different mammalian
      tissues is poorly characterized. The aim of this study was to map the expression
      of seven SLRPs (biglycan, versican, prolargin, fibromodulin, osteoglycin, decorin
      and lumican) in seven tissues (bone, cartilage, cruciate ligament, skin,
      ventricular myocardium, mitral valve and cornea) in young adult dogs using a
      combination of quantitative real-time PCR, immunohistochemistry and protein
      immunoblotting. Clear and consistent patterns of SLRP expression and distribution
      were identified for the seven tissues examined, with the greatest SLRP expression
      in cartilage, skin, cornea and mitral valve, and the least expression in
      myocardium. In general, lumican and prolargin had the greatest expression across
      the seven tissues whilst osteoglycin was the least abundantly expressed SLRP.
      These data provide a SLRP profile for different canine tissues which can inform
      future studies of SLRP expression in development and disease.

PMID- 22365844
TI  - Diagnosis and control of an outbreak of leptospirosis in goats with reproductive
      failure.
AB  - This study presents a Brazilian goat herd with reproductive failure over 2009
      2010, in which there were abortions (22/50; 44%), embryonic resorption (6/50;
      12%) and neonatal deaths (2/50; 4%). A diagnosis of leptospirosis was made, based
      on serology (microscopic agglutination test - MAT), bacterial culture, and
      polymerase chain reaction (PCR). Antibiotic therapy, specific vaccination
      protocols and changes in management practices were instigated. One year after the
      outbreak, diagnostic methods were repeated and reproductive performance re
      analysed. Soon after the outbreak, 61/125 (48.8%) of the goats were seropositive
      for Leptospira. Pure isolates of Leptospira were not obtained, but Leptospira PCR
      testing was positive in 48/50 (96%) urine samples. After 1 year only 4.2% were
      seropositive and the occurrence of reproductive problems decreased roughly 10
      fold, although five goats (10.4%) remained PCR-positive. A broad-based management
      approach, including serological and molecular diagnostic methods, vaccination,
      antibiotic treatment, and alteration of some environmental aspects, were critical
      to the control of this outbreak, thereby minimising subsequent reproductive
      failures and economic losses.

PMID- 22365845
TI  - Predictive simulation of gait at low gravity reveals skipping as the preferred
      locomotion strategy.
AB  - The investigation of gait strategies at low gravity environments gained momentum
      recently as manned missions to the Moon and to Mars are reconsidered. Although
      reports by astronauts of the Apollo missions indicate alternative gait strategies
      might be favored on the Moon, computational simulations and experimental
      investigations have been almost exclusively limited to the study of either
      walking or running, the locomotion modes preferred under Earth's gravity. In
      order to investigate the gait strategies likely to be favored at low gravity a
      series of predictive, computational simulations of gait are performed using a
      physiological model of the musculoskeletal system, without assuming any
      particular type of gait. A computationally efficient optimization strategy is
      utilized allowing for multiple simulations. The results reveal skipping as more
      efficient and less fatiguing than walking or running and suggest the existence of
      a walk-skip rather than a walk-run transition at low gravity. The results are
      expected to serve as a background to the design of experimental investigations of
      gait under simulated low gravity.

PMID- 22365846
TI  - Modified 3D scapular kinematic patterns for activities of daily living in painful
      shoulders with restricted mobility: a comparison with contralateral unaffected
      shoulders.
AB  - There is a lack of studies of 3D scapular kinematic patterns for patients with
      shoulder conditions comparing affected and contralateral nonaffected shoulders
      during self-care activities of daily living (ADL). In this study, we compared 48
      patients - 11 with glenohumeral osteoarthritis (GHOA), 20 with frozen shoulder
      (FS) and 17 with rotator cuff tendinopathies (RCT) - as they performed two ADL:
      hair combing and back washing. 3D scapular rotations and humerothoracic elevation
      (HTE) of the affected and contralateral nonaffected shoulders were recorded with
      use of a 6 degrees-of-freedom electromagnetic device. The HTE of affected and
      nonaffected shoulders were compared for each pathology group at rest and at the
      HTE used to perform the ADL: 30 degrees , 45 degrees  and 60 degrees  of HTE for
      hair combing, and 30 degrees  of HT elevation for back washing. For hair combing,
      mean peak HTE was significantly lower for affected than nonaffected shoulders.
      Mean scapular lateral rotation was significantly greater at each HTE degree for
      GHOA and RCT groups, and mean scapular posterior tilt was significantly lower at
      30 degrees  of HTE for the FS group. For back washing, mean peak HTE was lower
      for affected than nonaffected shoulders for the FS group only. Mean scapular
      medial rotation was significantly lower at 30 degrees  of HTE for the RCT group.
      3D scapular kinematics appear to be specific to the shoulder pathology and to the
      task studied. Specific scapular kinematic patterns must be considered for
      appropriate therapeutic management.

PMID- 22365847
TI  - Permeability analysis of scaffolds for bone tissue engineering.
AB  - Porous artificial bone substitutes, especially bone scaffolds coupled with
      osteobiologics, have been developed as an alternative to the traditional bone
      grafts. The bone scaffold should have a set of properties to provide mechanical
      support and simultaneously promote tissue regeneration. Among these properties,
      scaffold permeability is a determinant factor as it plays a major role in the
      ability for cells to penetrate the porous media and for nutrients to diffuse.
      Thus, the aim of this work is to characterize the permeability of the scaffold
      microstructure, using both computational and experimental methods.
      Computationally, permeability was estimated by homogenization methods applied to
      the problem of a fluid flow through a porous media. These homogenized
      permeability properties are compared with those obtained experimentally. For this
      purpose a simple experimental setup was used to test scaffolds built using Solid
      Free Form techniques. The obtained results show a linear correlation between the
      computational and the experimental permeability. Also, this study showed that
      permeability encompasses the influence of both porosity and pore size on mass
      transport, thus indicating its importance as a design parameter. This work
      indicates that the mathematical approach used to determine permeability may be
      useful as a scaffold design tool.

PMID- 22365848
TI  - The niche-dependent feedback loop generates a BMP activity gradient to determine
      the germline stem cell fate.
AB  - Stem cells interact with surrounding stromal cells (or niche) via signaling
      pathways to precisely balance stem cell self-renewal and differentiation.
      However, little is known about how niche signals are transduced dynamically and
      differentially to stem cells and their intermediate progeny and how the fate
      switch of stem cell to differentiating cell is initiated. The Drosophila ovarian
      germline stem cells (GSCs) have provided a heuristic model for studying the stem
      cell and niche interaction. Previous studies demonstrated that the niche
      dependent BMP signaling is essential for GSC self-renewal via silencing bam
      transcription in GSCs. We recently revealed that the Fused (Fu)/Smurf complex
      degrades the BMP type I receptor Tkv allowing for bam expression in
      differentiating cystoblasts (CBs). However, how the Fu is differentially
      regulated in GSCs and CBs remains unclear. Here we report that a niche-dependent
      feedback loop involving Tkv and Fu produces a steep gradient of BMP activity and
      determines GSC fate. Importantly, we show that Fu and graded BMP activity
      dynamically develop within an intermediate cell, the precursor of CBs, during GSC
      to-CB transition. Our mathematic modeling reveals a bistable behavior of the
      feedback-loop system in controlling the bam transcriptional on/off switch and
      determining GSC fate.

PMID- 22365849
TI  - Klp10A, a microtubule-depolymerizing kinesin-13, cooperates with CP110 to control
      Drosophila centriole length.
AB  - Klp10A is a kinesin-13 of Drosophila melanogaster that depolymerizes cytoplasmic
      microtubules. In interphase, it promotes microtubule catastrophe; in mitosis, it
      contributes to anaphase chromosome movement by enabling tubulin flux. Here we
      show that Klp10A also acts as a microtubule depolymerase on centriolar
      microtubules to regulate centriole length. Thus, in both cultured cell lines and
      the testes, absence of Klp10A leads to longer centrioles that show incomplete 9
      fold symmetry at their ends. These structures and associated pericentriolar
      material undergo fragmentation. We also show that in contrast to mammalian cells
      where depletion of CP110 leads to centriole elongation, in Drosophila cells it
      results in centriole length diminution that is overcome by codepletion of Klp10A
      to give longer centrioles than usual. We discuss how loss of centriole capping by
      CP110 might have different consequences for centriole length in mammalian and
      insect cells and also relate these findings to the functional interactions
      between mammalian CP110 and another kinesin-13, Kif24, that in mammalian cells
      regulates cilium formation.

PMID- 22365850
TI  - Chondroitin fragments are odorants that trigger fear behavior in fish.
AB  - The ability to detect and avoid predators is essential to survival. Various
      animals, from sea urchins to damselfly larvae, use injury of conspecifics to
      infer the presence of predators. In many fish, skin damage causes the release of
      chemicals that elicit escape and fear in members of the shoal. The chemical
      nature of the alarm substance ("Schreckstoff" in German), the neural circuits
      mediating the complex response, and the evolutionary origins of a signal with
      little obvious benefit to the sender, are unresolved. To address these questions,
      we use biochemical fractionation to molecularly characterize Schreckstoff.
      Although hypoxanthine-3 N-oxide has been proposed to be the alarm substance, it
      has not been reliably detected in the skin and there may be other active
      components. We show that the alarm substance is a mixture that includes the
      glycosaminoglycan (GAG) chondroitin. Purified chondroitins trigger fear
      responses. Like skin extract, chondroitins activate the mediodorsal posterior
      olfactory bulb, a region innervated by crypt neurons that has a unique projection
      to the habenula. These findings establish GAGs as a new class of odorants in
      fish, which trigger alarm behavior possibly via a specialized circuit.

PMID- 22365851
TI  - Pho85, Pcl1, and Hms1 signaling governs Candida albicans morphogenesis induced by
      high temperature or Hsp90 compromise.
AB  - BACKGROUND: Temperature exerts powerful control over development and virulence of
      diverse pathogens. In the leading human fungal pathogen, Candida albicans,
      temperature governs morphogenesis, a key virulence trait. Many cues that induce
      the yeast to filament transition are contingent on a minimum of 37 degrees C,
      whereas further elevation to 39 degrees C serves as an independent inducer. The
      molecular chaperone Hsp90 is a key regulator of C. albicans temperature-dependent
      morphogenesis. Compromise of Hsp90 function genetically, pharmacologically, or by
      elevated temperature induces filamentation in a manner that depends on protein
      kinase A signaling but is independent of the terminal transcription factor, Efg1.
      RESULTS: Here, we establish that despite morphological and regulatory
      differences, inhibition of Hsp90 induces a transcriptional profile similar to
      that induced by other filamentation cues and does so independently of Efg1.
      Further, we identify Hms1 as a transcriptional regulator required for
      morphogenesis induced by elevated temperature or Hsp90 compromise. Hms1 functions
      downstream of the cyclin Pcl1 and the cyclin-dependent kinase Pho85, both of
      which are required for temperature-dependent filamentation. Upon Hsp90
      inhibition, Hms1 binds to DNA elements involved in filamentous growth, including
      UME6 and RBT5, and regulates their expression, providing a mechanism through
      which Pho85, Pcl1, and Hms1 govern morphogenesis. Consistent with the importance
      of morphogenetic flexibility for virulence, deletion of C. albicans HMS1
      attenuates virulence in a metazoan model of infection. CONCLUSIONS: Thus, we
      establish a new mechanism through which Hsp90 orchestrates C. albicans
      morphogenesis, and define novel regulatory circuitry governing a temperature
      dependent developmental program, with broad implications for temperature sensing
      and virulence of microbial pathogens.

PMID- 22365852
TI  - Bub1 kinase and Sgo1 modulate pericentric chromatin in response to altered
      microtubule dynamics.
AB  - BACKGROUND: Tension sensing of bioriented chromosomes is essential for the
      fidelity of chromosome segregation. The spindle assembly checkpoint (SAC) conveys
      lack of tension or attachment to the anaphase promoting complex. Components of
      the SAC (Bub1) phosphorylate histone H2A (S121) and recruit the protector of
      cohesin, Shugoshin (Sgo1), to the inner centromere. How the chromatin structural
      modifications of the inner centromere are integrated into the tension sensing
      mechanisms and the checkpoint are not known. RESULTS: We have identified a
      Bub1/Sgo1-dependent structural change in the geometry and dynamics of
      kinetochores and the pericentric chromatin upon reduction of microtubule
      dynamics. The cluster of inner kinetochores contract, whereas the pericentric
      chromatin and cohesin that encircle spindle microtubules undergo a radial
      expansion. Despite its increased spatial distribution, the pericentric chromatin
      is less dynamic. The change in dynamics is due to histone H2A phosphorylation and
      Sgo1 recruitment to the pericentric chromatin, rather than microtubule dynamics.
      CONCLUSIONS: Bub1 and Sgo1 act as a rheostat to regulate the chromatin spring and
      maintain force balance. Through histone H2A S121 phosphorylation and recruitment
      of Sgo1, Bub1 kinase softens the chromatin spring in response to changes in
      microtubule dynamics. The geometric alteration of all 16 kinetochores and
      pericentric chromatin reflect global changes in the pericentromeric region and
      provide mechanisms for mechanically amplifying damage at a single kinetochore
      microtubule.

PMID- 22365853
TI  - Chromosome-wide gene silencing initiates Y degeneration in Drosophila.
AB  - Y degeneration is characterized by pseudogenization of its gene content, an
      accumulation of repetitive DNA and transcriptional inactivation associated with
      changes in chromatin structure. The sequence of events leading to genetically
      inert Y chromosomes, however, is unknown. Does the accumulation of nonsense and
      missense mutations at protein-coding Y genes trigger their transcriptional
      downregulation, or does transcriptional silencing of genes precede and expedite
      the decay of Y-linked genes at the amino acid level? Here, we study patterns of
      gene expression of the recently formed neo-Y chromosome of Drosophila albomicans,
      which displays few signs of degeneration of protein-coding genes. We show that
      chromosome-wide downregulation initiates the processes of Y evolution. This
      implies that the massive degeneration of protein-coding genes observed at many
      evolving Y-chromosomes may have limited deleterious effects, and instead, decay
      of regulatory functions is the initial trigger reducing fitness of the Y.

PMID- 22365854
TI  - "Do one, teach one": the new paradigm in general surgery residency training.

PMID- 22365855
TI  - Human patient simulator-based training ... for the olympics!

PMID- 22365856
TI  - Academic time at a level 1 trauma center: no resident, no problem?
AB  - BACKGROUND: Globally, the compliance of resident work-hour restrictions has no
      impact on trauma outcome. However, the effect of protected education time (PET),
      during which residents are unavailable to respond to trauma patients, has not
      been studied. We hypothesized that PET has no impact on the outcome of trauma
      patients. METHODS: We conducted a retrospective review of relevant patients at an
      academic level I trauma center. During PET, a trauma attending and advanced
      practice providers (APPs) responded to trauma activations. PGY1, 3, and 4
      residents were also available at all other times. The outcome of new trauma
      patient activations during Thursday morning 3-hours resident PET was compared
      with same time period on other weekdays (non-PET) using a univariate and
      multivariate analysis. RESULTS: From January 2005 to April 2010, a total of 5968
      trauma patients were entered in the registry. Of these, 178 patients (2.98%) were
      included for study (37 PET and 141 non-PET). The mean injury severity score (ISS)
      was 16.2. Although no significant difference were identified in mortality,
      complications, or length of stay (LOS), we do see that length of emergency
      department stay (ED-LOS) tends to be longer during PET, although not
      significantly (314 vs 381 minutes, p = 0.74). On the multiple logistic regression
      model, PET was not a significant factor of complications, LOS, or ED-LOS.
      CONCLUSIONS: Few trauma activations occur during PET. New trauma activations can
      be staffed safely by trauma activations and APPs. However, there could be some
      delays in transferring patients to appropriate disposition. Additional study is
      required to determine the effect of PET on existing trauma inpatients.

PMID- 22365857
TI  - An ERAS-based survey evaluating demographics, United States Medical Licensing
      Examination Performance, and research experience between American medical
      graduates and United States citizen international medical graduates: is the bar
      higher on the continent?
AB  - OBJECTIVE: To provide an assessment and comparison of the demographics, medical
      school academic performance, United States Medical Licensing Examination (USMLE)
      performance, and research experience between American Medical Graduate (AMG) and
      United States International Medical Graduate (USIMG) candidates who applied for
      and successfully matched into categorical general surgery residency programs.
      DESIGN: Data were obtained through the Electronic Residency Application Service
      (ERAS) and a post-match survey distributed to all applicants. SETTING: The study
      was conducted at a community-based, university-affiliated hospital. PARTICIPANTS:
      All United States citizen graduates of allopathic American medical schools or
      international medical schools, who were applying for a general surgery residency
      position at our institution. RESULTS: A total of 854 candidates applied,
      including 143 AMGs and 223 USIMGs. Seventy-two AMGs (50.3%) and 41 USIMGs (18.4%)
      were invited to interview (p < 0.0001). Mean USMLE step 1 scores were higher
      among USIMG applicants overall (USIMG: 212.1 +/- 14.9 vs AMG: 206.9 +/- 15.5; p <
      0.0005) and among those invited to interview (USIMG: 227.8 +/- 16.2 vs AMG: 215.5
      +/- 16.2; p < 0.0001). Seventy percent of AMGs matched into a categorical surgery
      residency compared with 31.6% of USIMGs (p < 0.001). Compared with AMGs, USIMGs
      applied to more programs (USIMG: 90.3 +/- 42.8 vs AMG: 52.1 +/- 26.4; p < 0.002),
      were offered fewer interviews (USIMG: 9.0 +/- 6.9 vs AMG: 20.9 +/- 13.7; p <
      0.0001), and subsequently ranked fewer programs (USIMG: 7.5 +/- 4.5 vs AMG: 12.5
      +/- 6.1; p < 0.0008). CONCLUSIONS: USIMGs require higher USMLE scores than their
      AMG counterparts to be considered for categorical general surgery residency
      positions. However, excellence on the USMLE neither ensures an invitation to
      interview nor categorical match success. A well-rounded application in
      conjunction with a practical application strategy is critical for USIMGs to
      achieve success in attaining a general surgery residency position.

PMID- 22365858
TI  - Assessing trainee impact on operative time for common general surgical procedures
      in ACS-NSQIP.
AB  - OBJECTIVE: To examine the effect of surgical trainee involvement on operative
      time for common surgical procedures. Laparoscopic appendectomy, laparoscopic
      cholecystectomy, and open inguinal hernia repair comprise 17.7% of the total
      cases sampled in the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) database. These cases are commonly performed by
      residents at varying levels of surgical training. STUDY DESIGN: A cross-sectional
      study was performed using American College of Surgeons National Surgical Quality
      Improvement Program data from 2005 through 2008 selecting patients undergoing
      laparoscopic appendectomy, laparoscopic cholecystectomy, and open inguinal hernia
      repair. The primary outcome was operative time and predictive variables were
      resident involvement and training level. Linear regression analysis was used to
      compare operative times between cases performed by an attending alone and those
      assisted by junior (postgraduate year 1-2) or senior (postgraduate year 3-5)
      trainees, adjusting for patient and operative factors. RESULTS: A total of
      115,535 surgical cases were included, with 65,364 (59%) performed with junior or
      senior surgical residents. Resident participation was associated with higher
      operative times with no significant differences between the junior and senior
      cohorts; this effect persisted after controlling for potential confounding
      factors. Operative time increased by 16.6 minutes (95% confidence interval, 16.2
      17.0) for junior residents and also by 16.6 minutes (95% confidence interval,
      16.2-16.9) for senior residents. CONCLUSIONS: Surgical trainees' participation in
      common surgical procedures is associated with an increase in total operative
      time, with no difference between trainee seniority levels. This finding may be
      significant in assessing the impact of residency training programs on hospital
      efficiency.

PMID- 22365859
TI  - Career development needs of vice chairs for education in departments of surgery.
AB  - AIM: To identify the career development needs Vice Chair for Education in Surgery
      Departments (VCESDs). METHODS: In all, 33 VCESDs were invited to complete an
      online survey to identify the scope of duties, scholarly activity, job
      satisfaction, and career development needs. RESULTS: A total of 29/33 (88%)
      VCESDs responded. Time constraints were the most frequent impediment for MDs vs.
      PhDs (p < 0.05). Dominant faculty development needs were conducting educational
      research (2.0 +/- 0.78 for MDs, 1.33 +/- 0.76 for PhDs), developing resident
      selection systems (1.68 +/- 0.73), and mentorship programs (1.95 +/- 0.77) for
      MDs, and developing teach the teacher programs (1 +/- 0), and program performance
      evaluation systems (1.33 +/- 0.76) for PhDs. The skills deemed to be of greatest
      importance were ability to communicate effectively (1.27 +/- 0.55), resolve
      personnel conflicts (1.32 +/- 0.57), and introduce change (1.41 +/- 0.59). PhDs
      revealed a greater need to learn strategies for dealing with disruptive faculty
      (1.0 +/- 0 vs 2.15 +/- 0.87). CONCLUSIONS: This information will inform the
      future career development of VCESDs and will assist Department Chairs who wish to
      recruit and retain VCESDs.

PMID- 22365860
TI  - Current approaches to journal club by general surgery programs within the
      Southwestern surgical congress.
AB  - BACKGROUND: Journal club (JC) is a well-recognized education tool for many
      postgraduate medical education programs. Journal club helps residents learn
      critical analytic skills and keep up to date with current medical practices. To
      our knowledge, there is minimal evidence in the current literature detailing
      modern JC practices of general surgery training programs. Our study attempts to
      define how general surgery residency programs are implementing JC in their
      training process. METHOD: We distributed by mail a 14-question survey to general
      surgery program directors within the Southwestern Surgical Congress. These
      surveys were redistributed 1 month after the initial attempt. The responses were
      collected and analyzed. Survey questions aimed to define JC practice
      characteristics, such as where JC is held, when JC is held, who directs JC, what
      journals are used, the perceived importance of JC, and average attendance.
      RESULTS: The surveys were sent to 32 program directors (PDs), which included 26
      university and 6 community-based programs. We received responses from 26 (81%)
      PDs. Ninety-two percent of the programs have a consistent journal club (JC). Most
      JCs meet monthly (64%) or weekly (16%). The meeting places ranged from conference
      rooms (60%), faculty homes (20%), restaurants (8%), or in the hospital (12%). The
      meeting times were divided between morning (29%), midday (29%), and evening
      (42%). Most JCs lasted between 1 and 2 hours (88%), reviewed 1-4 articles (88%),
      and are attended by more than 60% of residents routinely (75%). Half of the
      programs (50%) had 3-4 faculty members present during discussion; 29% of the
      programs had only 1-2 faculty present. The articles were selected from more than
      10 different journals. Seventy-five percent of the programs used the American
      Journal of Surgery and Annals of Surgery to find articles; only 13% of the
      programs used evidence-based reviews in surgery. PDs believe JC is very
      beneficial (42%), moderately beneficial (42%), or only fairly beneficial (16%).
      According to PDs, JC is most beneficial because it improves clinical knowledge
      (88%), initiates additional reading (62%), and improves American Board of Surgery
      In-Training Examination (ABSITE) scores (15%). CONCLUSION: Journal club has
      historically been an integral part of general surgery training. Our research
      indicates that journal club is still used widely as a beneficial educational
      resource and helps meet core competency requirements.

PMID- 22365861
TI  - Educational factors outweigh the importance of lifestyle factors for residency
      program applicants: an international comparative study.
AB  - OBJECTIVE: Although studies have been conducted to identify factors that attract
      students to a career in surgery, the relative importance of factors that attract
      students to a particular training program remains unknown. Comparative data
      between countries may provide insights and ultimately provide guidance to program
      directors as they seek to attract the best applicants to their program. DESIGN:
      Blinded written survey, scored 1-5 on a list of 26 factors divided into 3
      categories, including educational factors, lifestyle factors, and other. SETTING:
      Jichi Medical University, Japan and the David Geffen School of Medicine at
      University of California-Los Angeles. PARTICIPANTS: Japan residents (N = 125),
      Japan Medical Students (N = 68), United States Residents (N = 99), and United
      States Students (N = 55). RESULTS: All 4 groups surveyed judged faculty quality
      among the most important factors, with educational program quality, clinical
      experience and perceptions of resident happiness also rated among the most
      important. A comparison of factors consistent with lifestyle and factors
      consistent with the educational program found significantly (p < 0.05) higher
      scores for educational factors by 3 groups surveyed. CONCLUSIONS: Resident
      applicants are most interested in training program factors related to the quality
      of the educational program and the faculty. Issues such as salary, vacation,
      night call, location, or benefits are considered less important. The results in
      Japan and the United States were remarkably similar despite major differences in
      the educational system and debt load at the time of graduation. Program directors
      should communicate the value of those factors considered important by applicants
      as part of the recruitment process.

PMID- 22365862
TI  - Educational value of an intensive and structured interval practice laparoscopic
      training course for residents in obstetrics and gynecology: a four-year
      prospective, multi-institutional recruitment study.
AB  - OBJECTIVE: To assess the educational value of an ongoing interval practice
      laparoscopy training program among obstetrics and gynecology residents. DESIGN:
      Prospective cohort, multi-institutional recruitment study. We conducted
      structured laparoscopic training sessions for residents, using both inanimate and
      porcine models. The 6-day course was separated into two 3-day long modules
      conducted 2 months apart. A prospective evaluation of standardized tasks was
      performed using validated scales. Resident's performance was compared using the
      Student t test and Wilcoxon signed-rank test when appropriate. SETTING:
      International Center of Endoscopic Surgery (CICE), Clermont-Ferrand, France.
      PARTICIPANTS: 191 PGY2 or PGY3 residents from different institutions. RESULTS:
      Significant improvement in time and technical scores for both laparoscopic
      suturing and porcine nephrectomy was noted (p < 0.0001). After 2 months, we found
      no improvement in suturing time (p = 0.59) or technical scores (p = 0.62), and
      significant technical deterioration was observed for the right hand (p = 0.02).
      Porcine nephrectomy improvement remained significant after 2 months (p < 0.0001).
      CONCLUSIONS: Despite significant short-term educational value of interval
      practice in laparoscopic performance, some acquired skills seem to deteriorate
      faster than anticipated.

PMID- 22365863
TI  - Implementation of an objective structured clinical exam (OSCE) into orthopedic
      surgery residency training.
AB  - OBJECTIVE: While the musculoskeletal (MSK) physical examination (PE) is an
      essential part of a patient encounter, we believe it is an underemphasized
      component of orthopedic residency education and that resident PE skills may be
      lacking. The purpose of this investigation was to (1) assess the attitudes
      regarding PE teaching in orthopedic residencies today; (2) develop an MSK
      objective structured clinical examination (OSCE) to assess the MSK PE knowledge
      and skills of our orthopedic residents. DESIGN: Prospective, uncontrolled,
      observational. SETTING: A major Midwestern tertiary referral center and academic
      medical center. PARTICIPANTS: The orthopedic surgery residents in our program.
      Twenty-two of 24 completed the OSCE. RESULTS: Surveys showed that residents
      agreed that although learning the PE is important, there is not enough time in
      clinic to actually observe and critique a resident examining a patient. For the
      22 residents (postgraduate year [PGY] 2-5) who participated in the OSCE, the
      overall score was 66%. Scores were significantly better for the trauma scenario
      (78%; p < 0.05) than for the shoulder (67%), spine (64%), and knee (59%)
      encounters. The overall scores for each component of the OSCE were: (1) history
      53%; (2) PE 60%; (3) 5-question posttest 64%; and (4) communication skills 90%.
      CONCLUSIONS: We have exposed a deficiency in the PE knowledge and skills of our
      residents. Clinic time alone may be insufficient to both teach and learn the MSK
      PE. The use of a MSK OSCE, while novel in orthopedics, will allow more direct
      observation of our residents MSK PE skills and also allow us to follow resident
      skills longitudinally through their training. We hope that our efforts will
      encourage other programs to assess their PE curriculum and perhaps prompt change.

PMID- 22365864
TI  - Learning basic laparoscopic skills: a randomized controlled study comparing box
      trainer, virtual reality simulator, and mental training.
AB  - OBJECTIVES: The objectives of this study were (1) to compare different methods of
      learning basic laparoscopic skills using box trainer (BT), virtual reality
      simulator (VRS) and mental training (MT); and (2) to determine the most effective
      method of learning laparoscopic skills. DESIGN: Randomized controlled trial.
      SETTING: King's College, London. METHODS: 41 medical students were included in
      the study. After randomization, they were divided into 5 groups. Group 1 was the
      control group without training; group 2 was box trained; group 3 was also box
      trained with an additional practice session; group 4 was VRS trained; and group 5
      was solely mentally trained. The task was to cut out a circle marked on a
      stretchable material. All groups were assessed after 1 week on both BT and VRS.
      Four main parameters were assessed, namely time, precision, accuracy, and
      performance. RESULTS: Time: On BT assessment, the box-trained group with
      additional practice group 3 was the fastest, and the mental-trained group 5 was
      the slowest. On VRS assessment, the time difference between group 3 and the
      control group 1 was statistically significant. Precision: On BT assessment, the
      box-trained groups 2 and 3 scored high, and mental trained were low on precision.
      On VRS assessment, the VRS-trained group ranked at the top, and the MT group was
      at the bottom on precision. Accuracy: On BT assessment, the box-trained group 3
      was best and the mental-trained group was last. On VRS assessment, the VRS
      trained group 4 scored high closely followed by box-trained groups 2 and 3.
      Performance: On BT assessment, the box-trained group 3 ranked above all the other
      groups, and the mental-trained group ranked last. On VRS assessment, the VRS
      group 4 scored best, followed closely by box-trained groups 2 and 3. CONCLUSIONS:
      The skills learned on box training were reproducible on both VRS and BT. However,
      not all the skills learned on VRS were transferable to BT. Furthermore, VRS was
      found to be a reliable and the most convenient method of assessment. MT alone
      cannot replace conventional training.

PMID- 22365865
TI  - Learning styles of first-year orthopedic surgical residents at 1 accredited
      institution.
AB  - BACKGROUND: This study represents 1 arm of a 5-year prospective study
      investigating the learning styles of orthopedic residents and their surgical
      educators. METHODS: This project investigates the learning styles of the 2009
      2010 year 1 orthopedic surgical residents. A cross-sectional survey using the
      Kolb Learning Style Inventory was completed by 13 first year orthopedic
      residents. Direct 1-to-1 interviews were completed with the primary investigator
      and each participant using the Kolb Learning Style Inventory and learning styles
      were determined. RESULTS: Converging learning style was the most common among the
      residents (53.8%). Residents demonstrated a high tendency toward the learning
      skill of abstract conceptualization combined with active experimentation, and a
      transition from action-oriented to more reflective learning style with age and
      postgraduate education. CONCLUSIONS: These results may be useful in creating
      strategies specific to each learning style that will be offered to residents to
      enhance future teaching and learning.

PMID- 22365866
TI  - Learning surgical communication, leadership and teamwork through simulation.
AB  - BACKGROUND: In Australia and New Zealand, surgical trainees are expected to
      develop competencies across 9 domains. Although structured training is provided
      in several domains, there is little or no formal program for professionalism,
      communication, collaboration, and management and leadership. The Australian
      federal Department of Health and Aging funded a pilot course in simulation-based
      education to address these competencies for surgical trainees. This article
      describes the course and evaluation. METHODS: Course development: Content and
      methods drew on best-evidence for teaching and learning these competencies from
      other disciplines. Course evaluation: Participants completed surveys using rating
      scales and free text comments to identify aspects of the course that worked well
      and those that needed improvement. RESULTS: Eleven of 12 participants completed
      evaluation forms immediately after the course. Participants reported largely
      meeting learning objectives and valuing the educational methods. High levels of
      realism in simulations contributed to the ease with which participants immersed
      themselves in scenarios. CONCLUSIONS: This study demonstrates that a course
      designed to teach competencies in communication, teamwork, leadership, and the
      encompassing professionalism to surgical trainees is feasible. Although
      participants valued the content and methods, they identified areas for
      development. Limitations of the evaluation are highlighted, and further areas for
      research are identified.

PMID- 22365867
TI  - Mastery learning simulation-based curriculum for laparoscopic TEP inguinal hernia
      repair.
AB  - BACKGROUND: The laparoscopic totally extraperitoneal (TEP) inguinal herniorrhaphy
      requires 250 repairs to master. Simulation training could potentially accelerate
      this process. We describe the development, evaluation and implementation of a TEP
      mastery learning curriculum. DESIGN: We developed a 2-stage curriculum comprising
      online knowledge modules and skills practice on a simulator (the Guildford-MATTU
      TEP trainer; Limbs & Things, Ltd, Bristol, UK). Learners demonstrated mastery at
      each stage before advancing. The knowledge endpoint was a multiple-choice test.
      The skills endpoint was procedure time, as established by timing 5 experienced
      staff surgeons. Participants were proctored individually, receiving personalized
      feedback after each attempt until mastery time was achieved. The times to perform
      a simulated repair, number of attempts, and training time to reach mastery were
      compared between groups. RESULTS: The mastery time was established at 2 minutes.
      Nine medical students, 36 general surgery residents (PGY 1-5), and 3 surgery
      fellows participated as learners. All learners achieved the knowledge and skills
      mastery endpoints. For the skill endpoint, participants required a median of 69
      minutes (range, 13-193 minutes) and 16 simulated repairs (range, 7-27 repairs).
      The mean number of attempts and total training time to reach mastery varied by
      group (p < 0.001); more experienced residents required fewer attempts and less
      time to reach mastery. CONCLUSIONS: When training with a mastery learning-type
      simulation-based curriculum, surgical trainees can achieve the technical skill
      required to perform key portions of the TEP repair under artificial conditions
      with a performance similar to that of an expert, and are ready to move to the
      next phase of training in the operating room.

PMID- 22365868
TI  - Operating room fatigue: is your twentieth surgical knot as strong as your first?
AB  - OBJECTIVE: This study aimed to determine the tensile strength in a series of 20
      consecutively tied knots. Knot tying is a universally used technique in surgical
      procedures, and as such, knot integrity and security are essential. STUDY DESIGN:
      Twenty was the number of knots chosen as this is the average number of knots
      required for a vaginal hysterectomy. We used 0-0 gauge, nonexpired, polyglactin
      910 to tie 20 knots in succession with less than 20 seconds rest between knots.
      The knots were tied without a surgeon's knot and 4 additional square knots (1 = 1
      = 1 = 1 = 1). The knots were tied by 2 obstetrician/gynecologists investigators
      over the period of 2 weeks to minimize fatigue. The sutures were then soaked in
      0.9% sodium chloride for 60 seconds and subsequently transferred to a Chatillon
      LTCM-100 tensiometer (Ametek, Largo, Florida) where the tails were cut to 3 mm
      length. The force required to break the knots was recorded. To detect a
      difference over time while maintaining power of 80% with a type I error rate of
      5%, a minimum of 17 series of knots were needed (thus, 340 total knots after
      tying 20 knots per series). To buffer against unanticipated variability in the
      tensile strengths over time, we rounded the number of knot series up to 20, so a
      total of 400 knots were tied. RESULTS: A total of 800 knots were tied. All the
      sutures broke at the knot and 36% untied. For analyses, the data for each series
      of knots were collapsed into quarters (ie, knots 1-5, 6-10, 11-15, and 16-20). A
      repeated-measures analysis of variance found that there were no statistically
      significant differences between the four quartiles (p = 0.87). A paired samples t
      test comparing the first knots in each series with the last knots in each series
      showed no difference (p = 0.99). Similarly, a paired samples t-test comparing the
      first 10 knots to the last 10 knots showed no difference over time (p = 0.8). To
      determine whether there was a change in likelihood of knots coming untied, as
      more knots were tied, Cochran's Q was used to look across the entire series of 20
      knots. This analysis of proportions coming untied revealed no differences over
      time (p = 0.61). To compare across quarters, a Friedman test was used and
      similarly showed no change over time (p = 0.92). The different investigators were
      controlled for in the analysis as a covariate, which turned out to be
      statistically significant, p = 0.003. CONCLUSIONS: Under laboratory conditions,
      the order of knots tied does not change the tensile strength of the material.
      This would infer that fatigue does not influence the tensile strength for a
      series of 20 knots; however, additional studies with a larger number of knots
      series may be warranted.

PMID- 22365869
TI  - Self-regulated learning strategies used in surgical clerkship and the
      relationship with clinical achievement.
AB  - INTRODUCTION: Self-regulated learning indicates students' skills in controlling
      their own learning. Self-regulated learning, which a context-specific process,
      emphasizes autonomy and control. Students gain more autonomy with respect to
      learning in the clinical years. Examining the self-regulated learning skills of
      students in this period will provide important clues about the level at which
      students are ready to use these skills in real-life conditions. OBJECTIVES: The
      self-regulated learning strategies used by medical students in surgical clerkship
      were investigated in this study and their relation with clinical achievement was
      analyzed. METHODS: The study was conducted during the surgery clerkship of
      medical students. The participation rate was 94% (309 students). Motivated
      Strategies for Learning Questionnaire (MSLQ), a case-based examination, Objective
      Structured Clinical Examination (OSCE), and tutor evaluations for assessing
      achievement were used. The relationship between the Motivated Strategies for
      Learning Questionnaire scores of the students and clinical achievement was
      analyzed with multilinear regression analysis. RESULTS: The findings showed that
      students use self-regulated learning skills at medium levels during their surgery
      clerkship. A relationship between these skills and OSCE scores and tutor
      evaluations was determined. OSCE scores of the students were observed to increase
      in conjunction with increased self-efficacy levels. However, as students' beliefs
      regarding control over learning increased, OSCE scores decreased. No significant
      relationship was defined between self-regulated learning skills and case-based
      examination scores. CONCLUSIONS: We observed that a greater self-efficacy for
      learning resulted in higher OSCE scores. Conversely, students who believe that
      learning is a result of their own effort had lower OSCE scores.

PMID- 22365870
TI  - The effect of problem-based learning with cooperative-learning strategies in
      surgery clerkships.
AB  - BACKGROUND: Cooperative learning is used often as part of the problem-based
      learning (PBL) process. But PBL does not demand that students work together until
      all individuals master the material or share the rewards for their work together.
      OBJECTIVE: A cooperative learning and assessment structure was introduced in a
      PBL course in 10-week surgery clerkship, and the difference was evaluated between
      this method and conventional PBL in an acute abdominal pain module. METHODS: An
      experimental design was used. RESULTS: No significant differences in achievement
      were found between the study and control group. Both the study and control group
      students who scored low on the pretest made the greatest gains at the end of the
      education. Students in the cooperative learning group felt that cooperation
      helped them learn, it was fun to study and expressed satisfaction, but they
      complained about the amount of time the groups had to work together, difficulties
      of group work, and noise during the sessions. CONCLUSIONS: This study evaluated
      the impact of a cooperative learning technique (student team learning [STL]) in
      PBL and found no differences. The study confirms that a relationship exists
      between allocated study time and achievement, and student's satisfaction about
      using this technique.

PMID- 22365871
TI  - The American Board of Surgery Certifying Examination: a retrospective study of
      the decreasing pass rates and performance for first-time examinees.
AB  - BACKGROUND: There has been a noticeable decrease in the pass rate for the
      American Board of Surgery Certifying Examination during the last 5 years. We
      hypothesize that this decline is statistically significant, and we wish to
      determine whether the pass rates had any geographic patterns of distribution.
      METHODS: In this retrospective cohort trial, publically available electronic data
      sets of pass rates on the American Board of Surgery Certifying Examination were
      evaluated from the American Board of Surgery website. chi(2) tests were used to
      determine whether there was any association between the pass rates and the
      academic year. A descriptive geographic evaluation of program-specific pass rates
      for first-time examinees was also performed. RESULTS: From 2006 to 2010, there
      has been a 7% decrease in the pass rate for the American Board of Surgery
      Certifying Examination. A chi(2) test shows that there is a statistically
      significant association with the pass percentage on the American Board of Surgery
      Certifying Examination and the year (p < 0.0001). Subgroup analysis demonstrated
      a difference in pass rate between 2006 and 2007 (p = 0.02). Geographic analysis
      showed the pass rates for first-time examinees were the highest in Rhode Island
      (100%) and the lowest in Puerto Rico (63%) from 2005 to 2010. Three of the 5
      highest-performing states are on the Pacific Coast, and 4 of the 9 lowest
      performing states are in the southern United States. There are differences
      between these 2 groups of states (p < 0.001). CONCLUSIONS: There was a
      significant decrease in the pass rate for the American Board of Surgery
      Certifying Examination from 2006 to 2010. There also were some geographic
      patterns relating to first-time examinee performance from 2005 to 2010.

PMID- 22365872
TI  - Trauma leadership: does perception drive reality?
AB  - INTRODUCTION: Leadership plays a key role in trauma team management and might
      affect the efficiency of patient care. Our hypothesis was that a positive
      relationship exists between the trauma team members' perception of leadership and
      the efficiency of the injured patient's initial evaluation. METHODS: We conducted
      a prospective observational study evaluating trauma attending leadership (TAL)
      over 5 months at a level 1 trauma center. After the completion of patient care,
      trauma team members evaluated the TAL's ability using a modified Campbell
      Leadership Descriptor Survey tool. Scores ranged from 18 (ineffective leader) to
      72 (perfect score). Clinical efficiency was measured prospectively by recording
      the time needed to complete an advanced trauma life support (ATLS)-directed
      resuscitation. Assessment times across Leadership score groups were compared
      using Kruskal-Wallis and Mann-Whitney tests (p < 0.05, statistically
      significant). RESULTS: Seven attending physicians were included with a
      postfellowship experience ranging from <=1 to 11 years. The average leadership
      score was 59.8 (range, 27-72). Leadership scores were divided into 3 groups post
      facto: low (18-45), medium (46-67), and high (68-72). The teams directed by
      surgeons with low scores took significantly longer than teams directed by
      surgeons with high scores to complete the secondary survey (14 +/- 4 minutes in
      contrast to 11 +/- 2 minutes, p < 0.009) and to transport the patient for CT
      evaluation (19 +/- 5 minutes in contrast to 14 +/- 4 minutes; p < 0.001).
      Attending surgeon experience also affected clinical efficiency with teams
      directed by less experienced surgeons taking significantly longer to complete the
      primary survey (p < 0.05). CONCLUSION: The trauma team's perception of leadership
      is associated positively with clinical efficiency. As such, more formal
      leadership training could potentially improve patient care and should be included
      in surgical education.

PMID- 22365873
TI  - Invited commentary for "trauma leadership: does perception drive reality?".

PMID- 22365874
TI  - Boot cAMP: educational outcomes after 4 successive years of preparatory
      simulation-based training at onset of internship.
AB  - PURPOSE: Preparatory training for new trainees beginning residency has been used
      by a variety of programs across the country. To improve the clinical orientation
      process for our new postgraduate year (PGY)-1 residents, we developed an
      intensive preparatory training curriculum inclusive of cognitive and procedural
      skills, training activities considered essential for early PGY-1 clinical
      management. We define our surgical PGY-1 Boot Camp as preparatory simulation
      based training implemented at the onset of internship for introduction of skills
      necessary for basic surgical patient problem assessment and management. This
      orientation process includes exposure to simulated patient care encounters and
      technical skills training essential to new resident education. We report
      educational results of 4 successive years of Boot Camp training. Results were
      analyzed to determine if performance evidenced at onset of training was
      predictive of later educational outcomes. METHODS: Learners were PGY-1 residents,
      in both categorical and preliminary positions, at our medium-sized surgical
      residency program. Over a 4-year period, from July 2007 to July 2010, all 30 PGY
      1 residents starting surgical residency at our institution underwent specific
      preparatory didactic and skills training over a 9-week period. This consisted of
      mandatory weekly 1-hour and 3-hour sessions in the Simulation Center,
      representing a 4-fold increase in time in simulation laboratory training compared
      with the remainder of the year. Training occurred in 8 procedural skills areas
      (instrument use, knot-tying, suturing, laparoscopic skills, airway management,
      cardiopulmonary resuscitation, central venous catheter, and chest tube insertion)
      and in simulated patient care (shock, surgical emergencies, and respiratory,
      cardiac, and trauma management) using a variety of high- and low-tech simulation
      platforms. Faculty and senior residents served as instructors. All educational
      activities were structured to include preparatory materials, pretraining briefing
      sessions, and immediate in-training or post-training review and debriefing.
      Baseline cognitive skills were assessed with written tests on basic patient
      management. Post-Boot Camp tests similarly evaluated cognitive skills. Technical
      skills were assessed using a variety of task-specific instruments, and expressed
      as a mean score for all activities for each resident. All measurements were
      expressed as percent (%) best possible score. Cognitive and technical performance
      in Boot Camp was compared with subsequent clinical and core curriculum
      evaluations including weekly quiz scores, annual American Board of Surgery In
      Training Examination (ABSITE) scores, program in-training evaluations (New
      Innovations, Uniontown, Ohio), and operative assessment instrument scores (OP
      Rate, Baystate Medical Center, Springfield, Massachusetts) for the remainder of
      the PGY-1 year. RESULTS: Performance data were available for 30 PGY-1 residents
      over 4 years. Baseline cognitive skills were lower for the first year of Boot
      Camp as compared with subsequent years (71 +/- 13, 83 +/- 9, 84 +/- 11, and 86 +/
      6, respectively; p = 0.028, analysis of variance; ANOVA). Performance improved
      between pretests and final testing (81 +/- 11 vs 89 +/- 7; p < 0.001 paired t
      test). There was statistically significant correlation between Boot Camp final
      cognitive test results and American Board of Surgery In-Training Examination
      scores (p = 0.01; n = 22), but not quite significant for weekly curriculum quiz
      scores (p = 0.055; n = 22) and New Innovations cognitive assessments (p = 0.09; n
      = 25). Statistically significant correlation was also noted between Boot Camp
      mean overall skills and New Innovations technical skills assessments (p = 0.002;
      n = 25) and OP-Rate assessments (p = 0.01; n = 12). CONCLUSIONS: Individual
      simulation-based Boot Camp performance scores for cognitive and procedural skills
      assessments in PGY-1 residents correlate with subjective and objective clinical
      performance evaluations. This concurrent correlation with multiple traditional
      evaluation methods used to express competency in our residency program supports
      the use of Boot Camp performance measures as needs assessment tools as well as
      adjuncts to cumulative resident evaluation data.

PMID- 22365875
TI  - Safety and feasibility of the teaching assistant role of senior surgical
      residents: a prospective randomized study.
AB  - OBJECTIVE: The objective of the study was to assess the teaching assistant role
      of senior surgical residents. DESIGN: The study was designed in a prospective
      randomized fashion. All patients undergoing laparoscopic appendectomy were asked
      for consent. Consenters were assigned randomly to group A (attending directed) or
      group B (senior resident directed). In group A, all laparoscopic appendectomies
      were performed by junior residents (PGY-1, -2, or -3) with the attending faculty
      as the assistant. In group B, all cases were performed by junior residents (PGY
      1, -2, or -3) with the chief resident or PGY-4 acting as a teaching assistant.
      The allocation sequence was generated before the study by random permutations of
      120 assignments, 60 to each arm. The study ended after 60 laparoscopic
      appendectomies were recorded in each arm. SETTING: The study was conducted at San
      Joaquin General Hospital. This 200-bed, county teaching hospital has sponsored
      the general surgery residency program for the past 60 years. RESULTS: No
      significant difference in duration of surgery, hospital stay, postoperative
      complication, or baseline values was found between group A (attending faculty) or
      group B (senior resident). CONCLUSIONS: Senior surgical residents can act safely
      as teaching assistants for junior residents. Under faculty supervision, this
      teaching role can potentially enhance technical skills acquisition for senior
      residents in training programs without compromising patient safety.

PMID- 22365876
TI  - Novel educational approach for medical students: improved retention rates using
      interactive medical software compared with traditional lecture-based format.
AB  - BACKGROUND: Mannequin and computer-based simulators are useful for the practice
      of patient management, physical procedures, and competency. However, they are
      ineffective in teaching clinical medicine. StepStone Interactive Medical Software
      (SS) is a web-based medical learning modality that provides the user with a
      highly focused set of evaluative and interventional tasks to treat memorable
      virtual patients in a visual case-based format. OBJECTIVE: To determine whether
      the SS learning modality is superior to traditional lecture format in medical
      student learning and retention. METHODS: After Institutional Review Board (IRB)
      approval was obtained and the consents were signed, 30 third-year medical
      students were assigned randomly to 2 groups of 15 students each: The control
      group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond,
      Washington) about torsades de pointes (TdP) and pulseless electrical activity
      (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and
      PEA. A preintervention test was given to assess their baseline knowledge. An
      immediate postintervention test was given to both groups. Twenty-two days later,
      a long-term retention test was administered. The results were analyzed using a
      Student t test for continuous variables. RESULTS: The mean scores for the
      preintervention test in the control and SS groups were 44.9 +/- 3% and 44.1 +/-
      2%, respectively (p = 0.41). The mean scores for the postintervention test in the
      control and SS groups were 61.7 +/- 2% and 86.7 +/- 2%, respectively (p < 0.001).
      Improvement from baseline knowledge was calculated, and the mean improvement was
      16.8 +/- 3% in the control group and 42.5 +/- 2% in the SS group (p < 0.001). The
      long-term retention test revealed the mean scores of 55.8 +/- 3% in the control
      group and 70.1 +/- 3% in the SS group (p < 0.001). Long-term improvement from
      baseline knowledge was calculated and the control group improved by 10.9 +/- 4%,
      whereas the SS group improved by 26 +/- 3% (p = 0.002). CONCLUSIONS: The SS
      learning modality demonstrated a significant improvement in student learning
      retention compared to traditional didactic lecture format. SS is an effective web
      based medical education tool.

PMID- 22365877
TI  - Man is fashioned, not born: the contributions of George J. Heuer to surgical
      education.
AB  - George Heuer undertook his medical education and residency training in surgery at
      Johns Hopkins. He then joined the surgical faculty under Halsted. He became Chair
      of Surgery at the University of Cincinnati in 1922, where he developed the second
      formal surgical training program modeled on Halsted's principles. Subsequently,
      he became Chair of Surgery at Cornell where he founded another surgical
      residency. His training programs stressed broad and thorough experience, and he
      championed increasing resident responsibility and independence. The demonstrated
      efficacy of his surgical residencies assisted greatly in the formation of
      subsequent resident training programs across this country.

PMID- 22365878
TI  - Are great surgeons born?

PMID- 22365880
TI  - Value of tissue Doppler echocardiography in children with pulmonary hypertension.
AB  - BACKGROUND: The impact of pulmonary hypertension (PHT) on right ventricular and
      left ventricular (LV) function in children with PHT is unknown, and
      echocardiographic data combining conventional and Doppler tissue imaging (DTI) on
      PHT in children are sparse. METHODS: Forty-one children (18 male; mean age, 7.9
      +/- 5.6 years) with PHT and structurally normal hearts (27 with idiopathic PHT,
      14 with associated PHT) and 44 age-matched healthy controls were assessed using
      conventional echocardiography and DTI. RESULTS: Children with PHT had enlarged
      tricuspid valve diameters, right atrial areas, pulmonary artery dimensions, and
      LV eccentricity indices. In addition, pulmonary acceleration time and tricuspid
      annular plane systolic excursion were significantly reduced in patients compared
      with controls. DTI revealed that children with PHT had significantly lower
      systolic (S) and early diastolic (E) velocities at the tricuspid and septal
      levels. Despite preserved LV ejection fractions, left lateral free wall systolic
      velocities were significantly reduced in patients with PHT. Significantly reduced
      LV rapid filling velocities (E) suggested an underloaded left ventricle or LV
      diastolic dysfunction in children with PHT compared with controls. Pulmonary
      acceleration time and tricuspid annular plane systolic excursion correlated best
      with DTI systolic tricuspid and septal velocities. CONCLUSIONS: Despite not being
      evident on conventional two-dimensional echocardiography, LV systolic performance
      appears to be impaired in children with PHT. Quantitative DTI assessment of
      ventricular function and ventricular-ventricular interactions in this setting
      might provide further insights into the mechanisms leading to end-stage PHT and
      may guide clinicians to optimize antifailure treatment.

PMID- 22365879
TI  - Antimicrobial activity of sulfonamides containing 5-chloro-2-hydroxybenzaldehyde
      and 5-chloro-2-hydroxybenzoic acid scaffold.
AB  - A series of novel sulfonamides containing 5-chloro-2-hydroxybenzaldehyde or 5
      chloro-2-hydroxybenzoic acid scaffolds were designed, synthesized and
      characterized by IR, (1)H NMR and (13)C NMR. All ten target synthesized
      derivatives and starting sulfonamides were evaluated in vitro for the activity
      against Gram-positive and Gram-negative bacteria, fungi, Mycobacterium
      tuberculosis, Mycobacterium avium and Mycobacterium kansasii. The most active
      compound against methicillin-sensitive and methicillin-resistant Staphyloccoccus
      aureus was 5-chloro-N-{4-[N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl}-2
      hydroxybenzamide with MIC 15.62-31.25 MUmol/L. 4-Amino-N-(thiazol-2
      yl)benzenesulfonamide and 4-(5-chloro-2-hydroxybenzylideneamino)-N-(thiazol-2
      yl)benzenesulfonamide have shown the best activity against M. kansasii at the
      concentrations of 1-4 MUmol/L. The efficacy against other strains was weaker and
      the studied derivatives exhibited almost none antifungal potency.

PMID- 22365881
TI  - Left ventricular systolic dyssynchrony in pediatric and adolescent patients with
      congestive heart failure.
AB  - BACKGROUND: Echocardiographic measures of left ventricular (LV) dyssynchrony in
      pediatric patients with heart failure (HF) have not been adequately evaluated.
      The aim of this study was to evaluate LV systolic dyssynchrony in pediatric
      patients with HF and normal children. METHODS: Among a total of 68 patients, 22
      had HF and 46 were normal. Doppler tissue imaging, M-mode echocardiography, and
      pulsed-wave Doppler echocardiography were performed. Intraventricular
      dyssynchrony using the maximal difference in time to peak myocardial systolic
      contraction (Ts), the standard deviation of Ts of 12 LV segments, septal-to
      posterior wall motion delay, and interventricular dyssynchrony by measuring
      aortic and pulmonary pre-ejection delays were obtained. RESULTS: The maximal
      difference in Ts (patients with HF, 91.27 +/- 31.18 msec; controls, 45.93 +/-
      21.29 msec; P < .001), the standard deviation of Ts (patients with HF, 31.05 +/-
      10.68 msec; controls, 15.60 +/- 7.70 msec; P < .001), septal-to-posterior wall
      motion delay (patients with HF, 117.14 +/- 45.18 msec; controls, 48.69 +/- 16.63
      msec; P < .001) and interventricular dyssynchrony (patients with HF, 21.60 +/-
      16.27 msec; controls, 11.56 +/- 9.38 msec; P = .03) were significantly prolonged
      in the HF group. Defining systolic dyssynchrony as a standard deviation of Ts >
      31 msec (+2 standard deviations of normal controls) and a maximal difference in
      Ts > 89 msec in normal controls and 18 patients with HF due to dilated
      cardiomyopathy was included for analysis of systolic dyssynchrony; it was present
      in three (6.5%) and two (4.3%) controls and in nine (50%) and 10 (55%) patients
      with HF due to dilated cardiomyopathy, respectively. Low ejection fraction,
      elevated LV end-diastolic volume, and elevated LV end-systolic volume had
      significant correlations with systolic dyssynchrony. QRS duration was not
      significantly correlated with measures of dyssynchrony. CONCLUSIONS: Systolic
      mechanical dyssynchrony is common in pediatric patients with HF. QRS duration is
      not a determinant of systolic dyssynchrony in pediatric patients.
      Echocardiographic measurements of systolic dyssynchrony are feasible in pediatric
      patients.

PMID- 22365882
TI  - Use of SBA-15 for furosemide oral delivery enhancement.
AB  - The objective of this research was to realize a new oral solid dosage form in
      order to improve the release of furosemide (FURO) in its preferential absorption
      region. In fact FURO is a drug labeled in class IV of the Biopharmaceutical
      Classification System (BCS) characterized by low and variable bioavailability due
      to both low solubility and low permeability and because of its weakly acid nature
      is preferentially absorbed in the stomach whereas its solubility is hampered.
      FURO was included in the mesoporous silica material SBA-15 obtaining an inorganic
      organic compound fully characterized by: thermogravimetric analysis (TGA), X-ray
      Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Fourier
      Transform Infrared Spectroscopy (FT-IR) and nitrogen adsorption-desorption
      analysis and then submitted to in vitro dissolution. The results showed a
      remarkable dissolution rate improvement in comparison to the crystalline drug and
      to the marketed product Lasix(r). The inclusion product was also submitted to
      physical stability studies that revealed the matrix ability to prevent re
      organization in crystal nucleus of the drug molecules.

PMID- 22365883
TI  - Development and validation of a vitiligo-specific quality-of-life instrument
      (VitiQoL).
AB  - BACKGROUND: Vitiligo significantly affects a person's health-related quality of
      life (HRQL). Although a small number of generic, and disease-specific,
      dermatologic HRQL measures exist, currently no vitiligo-specific instrument is
      available to capture disease-targeted concerns and issues. OBJECTIVE: We sought
      to develop and validate a vitiligo-specific self-report instrument for HRQL.
      METHODS: A pool of vitiligo-specific items was created based on in-depth
      interviews with patients with vitiligo (n = 16) and their responses to items in
      several previously validated HRQL measures. These items comprising our new
      instrument, VitiQoL, along with Skindex-16 and Dermatology Life Quality Index
      were administered to patients with vitiligo (n = 90) at two academic centers.
      This new instrument was validated using psychometric analysis. RESULTS: The
      VitiQoL items showed high internal consistency (Cronbach alpha = 0.935).
      Exploratory factor analysis demonstrated 3 factors: participation limitation,
      stigma, and behavior. Concurrent validity was evidenced by large correlations
      between self-reported severity and VitiQoL scores (r = 0.51). Known groups
      validity was demonstrated for the VitiQoL behavior subscale between individuals
      with exposed and unexposed patches (P = .01). Convergent validity was shown by
      strong correlations between VitiQoL and outside dermatology scales measuring
      similar constructs (Skindex-16, r = 0.82; Dermatology Life Quality Index, r =
      0.83). LIMITATIONS: Potential selection bias was a limitation as most patients
      were recruited from academic centers. Reliability of the instrument was tested
      only with internal consistency and not reproducibility. Responsiveness of the
      instrument was not tested because of the prolonged time course necessary to
      observe clinically significant change in vitiligo. CONCLUSION: VitiQoL is a
      reliable and valid HRQL instrument.

PMID- 22365885
TI  - Repertoire of human natural anti-glycan immunoglobulins. Do we have auto
      antibodies?
AB  - BACKGROUND: Profiling of donor's antibodies using glycan arrays demonstrated
      presence of antibodies capable of binding to >100 mammalian glycans or their
      fragments. For example, relatively high binding to Galalpha1-4Galbeta1-4GlcNAc
      (P(1)), Galalpha1-4Galbeta1-4Glc (P(k)), Galbeta1-3GlcNAc (Le(c)), 4-O-SuGalbeta1
      4GlcNAc, and GalNAcalpha1-3GalNAc (Fs) was found in all tested individuals.
      Affinity isolation using hapten-specific chromatography in combination with
      epitope mapping revealed their glycotopes. Notably, a significant part of the
      antibodies was capable of recognizing a fragment of larger glycans, for example, 
      Galbeta1-4Glc of glycolipids, or Fucalpha1-3GlcNAc motif of Le(X)/Le(Y) antigens.
      Their epitope specificity did not vary between different healthy individuals.
      Nominally, all the mentioned immunoglobulins could be classified as auto
      antibodies. METHODS: In this work we re-evaluated results published earlier and
      analyzed new data to address the question why autologous antibodies found in
      healthy individuals do not cause severe auto-immune reactions. RESULTS: In all
      cases the presumably "auto" antibodies were found to bind short fragments
      "subtracted" from larger glycans whereas recognition of the same fragment in the
      context of the whole natural chain was completely abolished. Thus, in spite of
      numerous formally positive signals observed on the printed glycan array, we are
      yet unable to identify in blood serum of healthy individuals true auto-antibodies
      capable of binding carbohydrate chains in their naturally occurring form. GENERAL
      SIGNIFICANCE: The identified natural anti-glycan antibodies were found to be
      specific, high-titer and population conservative immunoglobulins - all of this
      suggesting as yet unknown biological role(s) of the studied proteins. This
      article is part of a Special Issue entitled Glycoproteomics.

PMID- 22365886
TI  - Phonation interval modification and speech performance quality during fluency
      inducing conditions by adults who stutter.
AB  - PURPOSE: To relate changes in four variables previously defined as characteristic
      of normally fluent speech to changes in phonatory behavior during oral reading by
      persons who stutter (PWS) and normally fluent controls under multiple fluency
      inducing (FI) conditions. METHOD: Twelve PWS and 12 controls each completed 4 ABA
      experiments. During A phases, participants read normally. B phases were 4
      different FI conditions: auditory masking, chorus reading, whispering, and
      rhythmic stimulation. Dependent variables were the durations of accelerometer
      recorded phonated intervals; self-judged speech effort; and observer-judged
      stuttering frequency, speech rate, and speech naturalness. The method enabled a
      systematic replication of Ingham et al. (2009). RESULTS: All FI conditions
      resulted in decreased stuttering and decreases in the number of short phonated
      intervals, as compared with baseline conditions, but the only FI condition that
      satisfied all four characteristics of normally fluent speech was chorus reading.
      Increases in longer phonated intervals were associated with decreased stuttering
      but also with poorer naturalness and/or increased speech effort. Previous
      findings concerning the effects of FI conditions on speech naturalness and effort
      were replicated. CONCLUSIONS: Measuring all relevant characteristics of normally
      fluent speech, in the context of treatments that aim to reduce the occurrence of
      short-duration PIs, may aid the search for an explanation of the nature of
      stuttering and may also maximize treatment outcomes for adults who stutter.
      LEARNING OUTCOMES: The reader will be able to (1) understand the differential
      effects of four well established fluency-inducing conditions on the quality of
      fluency of adult PWS and controls, (2) learn how intervals of phonation are
      modified during these conditions and (3) how the duration of specific intervals
      of phonation may be identified for their potential application in stuttering
      treatment.

PMID- 22365887
TI  - The separate and interactive effects of drinking motives and social anxiety
      symptoms in predicting drinking outcomes.
AB  - PURPOSE: Our goal was to test the separate and interactive effects of drinking
      motives and social anxiety symptoms in predicting drinking-related consumption
      and problems. METHODS: Participants (N=730; 59.7% female) were undergraduate
      college students who completed measures of social anxiety symptoms, drinking
      motives, alcohol consumption, and drinking problems. RESULTS: Greater social
      anxiety symptoms were significantly associated with less alcohol consumption, and
      there was some evidence that greater social anxiety symptoms were also associated
      with greater alcohol-relevant problems. Significant interactions between social
      anxiety and motives indicated that a) alcohol use was most pronounced for
      individuals high in enhancement motives and low in social anxiety symptoms; and
      b) among participants low in coping motives, drinking problems were greater for
      individuals high (vs. low) in social anxiety symptoms. CONCLUSIONS: More fully
      identifying the individual difference factors that link social anxiety symptoms
      with drinking outcomes is important for informing prevention and intervention
      approaches.

PMID- 22365888
TI  - Spatial and temporal expression of folate-related transporters and metabolic
      enzymes during mouse placental development.
AB  - It is well understood that maternal folate deficiency can cause abnormal fetal
      development. However, the extent to which placental development and function are
      also dependent upon folate uptake and metabolism remains unclear. To understand
      which trophoblast cell types may be affected by folate deficiency or abnormal
      folate metabolism, we completed a comprehensive spatial and temporal protein
      expression analysis of folate receptor (Folr), folate transporters (proton
      coupled folate receptor [Slc46a1 or PCFT] and reduced folate carrier-1 [Rfc1])
      and folate metabolic enzymes (5,10-methylenetetrahydrofolate reductase [Mthfr]
      and methionine synthase [Mtr]) in histological sections of mouse placentas from
      early development (E8.5) until term (E18.5). We observed that the highest level
      of protein expression was during early development (E8.5-E10.5), prior to the
      formation of the three main layers of the mature placenta suggesting that folate
      uptake and metabolism may be required for placental development, itself. As
      expected, the labyrinth trophoblast cells, which are responsible for nutrient
      transport, expressed these proteins throughout pregnancy, including robust
      expression in the sinusoidal trophoblast giant cells that line the maternal blood
      spaces. Other trophoblast giant cell (TGC) subtypes (parietal-TGCs and canal
      TGCs), whose function does not include nutrient transport, expressed folate
      transporters and enzymes from E8.5 onwards. Remarkably, these proteins were also
      detected in glycogen trophoblast cells from E12.5-E18.5 suggesting a new role in
      folate uptake and metabolism for these cells. Together, these data provide
      evidence that folate may be necessary for normal placental development and
      function, and perturbations in its availability or metabolism may lead to
      secondary effects on fetal development.

PMID- 22365889
TI  - Human placentation from nidation to 5 weeks of gestation. Part II: Tools to model
      the crucial first days.
AB  - Human pregnancy is unusual with respect to monthly spontaneous decidualisation as
      well as the degree of placental invasion and interaction with the decidualised
      endometrial stroma. This review covers in vivo animal models and in vitro cell
      culture models that have been used to study the earliest stages of human
      implantation and placentation from nidation to 5 weeks of gestation. The field
      has expanded rapidly in recent years due to the generation of human embryonic
      stem cell lines and the ability of some scientists to culture human blastocysts.
      These models have enabled researchers to begin to elucidate the interactions
      involved in human blastocyst apposition, adhesion and implantation. However, we
      still understand very little about the differentiation processes involved in the
      formation of the placenta. Continued improvements to current models, including
      the potential isolation of a human trophoblast stem cell, will significantly
      enhance our ability to define the molecular and structural events occurring
      during human implantation and early placental development.

PMID- 22365890
TI  - Acatalasemia and diabetes mellitus.
AB  - The enzyme catalase catalyzes the breakdown of hydrogen peroxide into oxygen and
      water. It is the main regulator of hydrogen peroxide metabolism. Hydrogen
      peroxide is a highly reactive small molecule formed as a natural byproducts of
      energy metabolism. Excessive concentrations may cause significant damages to
      protein, DNA, RNA and lipids. Low levels in muscle cells, facilitate insulin
      signaling. Acatalasemia is a result of the homozygous mutations in the catalase
      gene, has a worldwide distribution with 12 known mutations. Increased hydrogen
      peroxide, due to catalase deficiency, plays a role in the pathogenesis of several
      diseases such as diabetes mellitus. Diabetes mellitus is a disorder caused by
      multiple genetic and environmental factors. Examination of Hungarian diabetic and
      acatalasemic patients showed that an increased frequency of catalase gene
      mutations exists among diabetes patients. Inherited catalase deficiency may
      increase the risk of type 2 diabetes mellitus, especially for females. Early
      onset of type 2 diabetes occurs with inherited catalase deficiency. Low levels of
      SOD and glutathione peroxidase could contribute to complications caused by
      increased oxidative stress.

PMID- 22365891
TI  - Scholarship in education: the currency for career development for clinician
      educators in gastroenterology and hepatology.

PMID- 22365892
TI  - Quercetin prevents ethanol-induced dyslipidemia and mitochondrial oxidative
      damage.
AB  - Lipid metabolism disorder and oxidative stress play an important role on the
      development and progression of alcoholic liver disease (ALD), and mitochondria
      compartment is presumed as the main source and susceptible target of
      intracellular ROS. The objective of this study was to evaluate the protective
      effect of quercetin, a naturally occurring flavonoids possessing both antioxidant
      and hypolipidemic effect, on ethanol-induced dyslipidemia and oxidative damage
      focused on mitochondria. Chronic alcohol administration for adult male rats (4.0
      g/kg for 90 days) resulted in the leakage of alanine and especially aspartate
      aminotransferases, and morphological malformation mainly evidenced by sustained
      lipid infiltration and degenerative changes on mitochondria and rough endoplasmic
      reticulum, which was markedly alleviated by quercetin (100 mg/kg.bw.)
      pretreatment. Furthermore, quercetin prophylaxis evidently ameliorated ethanol
      stimulated mitochondrial dysfunction manifested by decreased membrane potential
      and induced permeability transition though suppressing glutathione depletion,
      enzymatic inactivation of manganese superoxide dismutase and glutathione
      peroxidase, ROS over-generation, and lipid peroxidation in mitochondria.
      Quercetin, thus, may protect rat, especially hepatic mitochondria, from chronic
      ethanol toxicity through its hypolipidemic effect and antioxidative role,
      highlighting a promising preventive strategy for ALD by naturally occurring
      phytochemicals.

PMID- 22365893
TI  - Evaluation of pharyngeal airway space amongst different skeletal patterns.
AB  - The aim of the present study was to evaluate the dimensions of the pharyngeal
      airway space (PAS) in awake, upright children with different anteroposterior
      skeletal patterns using cone beam computed tomography (CBCT). The volume, area,
      minimum axial area and seven linear measurements of PAS were obtained from the
      CBCT images of 50 children (mean age 9.16 years). The patients were divided in
      two groups according to the ANB angle (group I 2 degrees  <= ANB <= 5 degrees ;
      group II ANB > 5 degrees ). Means and standard deviations of each variable were
      compared and correlated using independent t-test and Pearson's correlation test.
      There were statistically significant differences in the following parameters:
      angle formed by the intersection between NA and NB lines (p<0.001), angle formed
      by the intersection between SN and NB lines (p<0.05), Minimal pharyngeal airway
      space between the uvula and the posterior pharyngeal wall (p<0.05), airway volume
      (p<0.01), airway area (p<0.01) and minimum axial area (p<0.05). The
      anteroposterior cephalometric variable SNB had positive correlation with the
      variables PAS-UP (p<0.01), Minimal pharyngeal airway space between the uvula tip
      and the posterior pharyngeal wall (p<0.05), Pharyngeal airway space on mandibular
      line (p<0.05), Minimal pharyngeal airway space between the back of the tongue and
      the posterior pharyngeal wall (p<0.05), volume airway (p<0.05), airway area
      (p<0.05) and minimum axial area (p<0.05). The vertical cephalometric variables
      angle formed by the intersection between SN and GoGn lines (p<0.05) and angle
      formed by the intersection between FH and mandible plane (p<0.05) showed negative
      correlation with PAS-UT. These results showed that PAS was statistically larger
      in group I than group II, indicating that the dimensions of the PAS are affected
      by different anteroposterior skeletal patterns.

PMID- 22365894
TI  - Intrathecal baclofen for progressive neurological disease in childhood.

PMID- 22365895
TI  - Role of cigarette sensory cues in modifying puffing topography.
AB  - BACKGROUND: Human puffing topography promotes tobacco dependence by ensuring
      nicotine delivery, but the factors that determine puffing behavior are not well
      explained by existing models. Chemosensory cues generated by variations in
      cigarette product design features may serve as conditioned cues to allow the
      smoker to optimize nicotine delivery by adjusting puffing topography. Internal
      tobacco industry research documents were reviewed to understand the influence of
      sensory cues on puffing topography, and to examine how the tobacco industry has
      designed cigarettes, including modified risk tobacco products (MRTPs), to enhance
      puffing behavior to optimize nicotine delivery and product acceptability.
      METHODS: Relevant internal tobacco industry documents were identified using
      systematic searching with key search terms and phrases, and then snowball
      sampling method was applied to establish further search terms. RESULTS: Modern
      cigarettes are designed by cigarette manufacturers to provide sensory
      characteristics that not only maintain appeal, but provide cues which inform
      puffing intensity. Alterations in the chemosensory cues provided in tobacco smoke
      play an important role in modifying smoking behavior independently of the central
      effects of nicotine. CONCLUSIONS: An associative learning model is proposed to
      explain the influence of chemosensory cues on variation in puffing topography.
      These cues are delivered via tobacco smoke and are moderated by design features
      and additives used in cigarettes. The implications for regulation of design
      features of modified risk tobacco products, which may act to promote intensive
      puffing while lowering risk perceptions, are discussed.

PMID- 22365896
TI  - Does the "gateway" sequence increase prediction of cannabis use disorder
      development beyond deviant socialization? Implications for prevention practice
      and policy.
AB  - BACKGROUND: This study was conducted to test whether non-normative socialization
      mediates the association between transmissible risk measured in childhood and
      cannabis use disorder manifested by young adulthood, and whether the sequence of
      drug use initiation ("gateway", i.e., consuming legal drugs before cannabis, or
      the reverse) increases accuracy of prediction of cannabis use disorder. METHODS:
      Sons of fathers with or without substance use disorders (SUDs) related to illicit
      drugs were tracked from 10-12 to 22 years of age to model the association between
      transmissible risk for SUD, socialization (peer deviance), order of drug use
      initiation ("gateway" or reverse sequence), and development of cannabis use
      disorder. Path analysis was used to evaluate relationships among the variables.
      RESULTS: Non-normative socialization mediates the association between
      transmissible risk measured during childhood and cannabis use disorder manifest
      by young adulthood. The sequence of drug use initiation did not contribute
      additional explanatory information to the model. CONCLUSIONS: The order of drug
      use initiation does not play a substantial role in the etiology of cannabis use
      disorder.

PMID- 22365897
TI  - Separate and combined psychopharmacological effects of alprazolam and oxycodone
      in healthy volunteers.
AB  - BACKGROUND: There are epidemiological data indicating that medical and/or
      nonmedical use of prescription opioids oftentimes involves concurrent use of
      other substances. One of those substances is benzodiazepines. It would be of
      relevance to characterize the effects of an opioid and a benzodiazepine when
      taken together to determine if measures related to abuse liability-related
      effects and psychomotor performance impairment are increased compared to when the
      drugs are taken alone. METHODS: Twenty volunteers participated in a crossover,
      randomized, double-blind study in which they received placebo, 0.5mg alprazolam,
      10mg oxycodone, and 0.5mg alprazolam combined with 10 mg oxycodone, all p.o.
      Subjective, psychomotor, and physiological measures were assessed during each of
      the four sessions. RESULTS: Oxycodone by itself increased drug liking and "take
      again" ratings relative to placebo, but these ratings were not increased when
      oxycodone was taken with alprazolam, which by itself did not increase either of
      these ratings. The two drugs in combination produced stronger effects (larger in
      magnitude or longer lasting) than when either was taken alone on a number of
      measures, including psychomotor performance impairment. CONCLUSIONS: In healthy
      volunteers, abuse liability-related subjective effects of oxycodone were not
      enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs
      were taken together, and thus, this is of significant concern from a public
      safety standpoint.

PMID- 22365899
TI  - Asymmetric switch-costs and ERPs reveal facial identity dominance over
      expression.
AB  - Previous studies on face processing have revealed an asymmetric overlap between
      identity and expression, as identity is processed irrespective of expression
      while expression processing partly depends on identity. To investigate whether
      this relative interaction is caused by dominance of identity over expression,
      participants performed familiarity and expression judgments during task
      switching. This paradigm reveals task-set dominance with a paradoxical asymmetric
      switch-cost (i.e., greater difference between switch and repeat trials when
      switching toward the dominant task). Event-related potentials (ERPs) were
      recorded to find the neural signature of the asymmetric cost. As expected,
      greater switch-cost was shown in the familiarity task with respect to response
      times, indicating its dominance over the expression task. Moreover, a left-sided
      ERP correlate of this effect was observed at the level of the frontal N2
      component, interpreted as an index of modulations in endogenous executive
      control. Altogether, these results confirm the overlap between identity and
      expression during face processing and further indicate their relative dominance.

PMID- 22365898
TI  - Risk factors for adolescent smoking: parental smoking and the mediating role of
      nicotine dependence.
AB  - BACKGROUND: Parental smoking and early-emerging nicotine dependence symptoms are
      well-documented risk factors for adolescent smoking. However, very little is
      known about the mediating pathways through which these risk factors may act, or
      whether parental smoking may cause or signal early-emerging nicotine dependence
      symptoms. METHODS: Data were drawn from the longitudinal Social and Emotional
      Contexts of Adolescent Smoking Patterns Study. Adolescents who had smoked under
      100 cigarettes in their lifetime (n=594; low-exposure group) and adolescents who
      had smoked over 100 cigarettes, but fewer than 5 cigarettes per day (n=152) were
      included in the analyses. Path analysis was performed on longitudinal data to
      investigate the association between parental smoking and smoking frequency at the
      48 months follow-up, both directly and through mediating variables of smoking
      frequency, smoking quantity, and nicotine dependence. RESULTS: Father's smoking
      was associated with higher adolescent nicotine dependence scores at the baseline
      assessment wave. Structural equation modeling revealed that mother's smoking at
      baseline was associated with adolescent's smoking frequency at the 48-month
      follow-up, and its effect was partially mediated by both smoking frequency and
      nicotine dependence among low-exposure adolescent smokers. CONCLUSIONS: Parental
      smoking is a risk factor for future smoking in low-exposure adolescent smokers,
      above and beyond the risks posed by smoking behavior and nicotine dependence.
      Moreover, parental smoking is associated with early-onset nicotine dependence in
      low-exposure adolescent smokers. As an easily measureable risk factor, parent
      smoking status can be used to identify and intervene with novice adolescent
      smokers who are at high risk for chronic smoking behavior.

PMID- 22365900
TI  - An inhibition effect in the temporal constrains of attentional selection: the
      Backward Blink.
AB  - The study aims at investigating the dynamics of visual information processing
      during sequential control of attentional selection. By combining two different
      traditional paradigms we show for the first time that during rapid selection of
      visual targets, encoding of a new target stimulus is facilitated by suppression
      of the preceding relevant stimulus category (Backward Blink; BB). Such inhibition
      would operate to reduce interference from previously stored information, in order
      to facilitate the instantiation of a new attentional episode. Results suggest
      that the same underlying inhibitory mechanism might contribute to two different
      attentional effects, specifically, the switch cost and the Attentional Blink,
      suggesting a general inhibitory mechanism of attentional control, with broad
      implications for understanding how the brain perceives any task-relevant
      stimulus.

PMID- 22365901
TI  - Myometry revealed medication-induced decrease in resting skeletal muscle
      stiffness in Parkinson's disease patients.
AB  - BACKGROUND: Based on combined analysis of clinical assessment of parkinsonian
      rigidity (constant resistance force generated during passive movement in a
      joint), electromyography and/or dynamometry many studies showed objectively that
      anti-parkinsonian medication decreases the rigidity in Parkinson's disease (PD).
      Rigidity-related changes in resting muscle stiffness (changed muscle's mechanical
      property related to its structural changes and changed neural drive) in PD
      patients have been revealed by myometry, a simple, sensitive, and reliable method
      for measuring mechanical properties in human soft tissues. However, an
      application of myometry in estimation of medication effects on the PD rigidity
      related muscle stiffness has not been reported yet. Therefore, our study aimed to
      assess medication-induced changes in resting muscle stiffness in PD patients
      using myometry. METHODS: We measured resting muscle stiffness by myometry and
      recorded a surface electromyogram of relaxed biceps brachii, brachioradialis and
      triceps brachii muscles in ten patients with PD (age: 51-80 years; Hoehn and Yahr
      stage: 2.5-4) during medication on-phase (when subjects felt best comfort and
      fitness after medication: Levodopa, Piribedil, Ropinirol) and medication off
      phase (12h after withdrawal of the medication). FINDINGS: Our patients had
      significantly lower myometric stiffness and electromyogram amplitude in all
      tested muscles, and also lower clinical rigidity scores during the medication on
      phase compared with the medication off-phase. INTERPRETATION: Myometry revealed
      that anti-parkinsonian medication decreases not only rigidity in PD, but also
      rigidity-related stiffness in resting skeletal muscles in PD patients. These
      findings show that myometry can enrich neurological practice, by allowing
      objective and reliable assessment of parkinsonian rigidity treatment
      effectiveness.

PMID- 22365902
TI  - Are plasmacytoid dendritic cells the misguided sentinels of malarial immunity?
AB  - Dendritic cells (DCs), the sentinels of immunity, reside in almost every organ of
      the body. These cells are responsible for initiating immune responses against
      infectious agents. DCs are divided into different subsets based on their
      biological functions, with plasmacytoid DCs (pDCs) and conventional DCs (cDCs)
      being two major populations. The ability of DCs to protect against malaria
      infection was recently questioned when pDCs were reported to be a reservoir for
      rodent Plasmodium spp. in the spleen. This opinion article explores how the
      occupation of pDCs by the parasite may corrupt immunity against malaria.

PMID- 22365903
TI  - Antigen presentation by endothelial cells: what role in the pathophysiology of
      malaria?
AB  - Disruption of the endothelial cell (EC) barrier leads to pathology via edema and
      inflammation. During infections, pathogens are known to invade the EC barrier and
      modulate vascular permeability. However, ECs are semi-professional antigen
      presenting cells, triggering T-cell costimulation and specific immune-cell
      activation. This in turn leads to the release of inflammatory mediators and the
      destruction of infected cells by effectors such as CD8(+) T-cells. During
      malaria, transfer of parasite antigens to the EC surface is now established. At
      the same time, CD8 activation seems to play a major role in cerebral malaria. We
      summarize here some of the pathways leading to antigen presentation by ECs and
      address the involvement of these mechanisms in the pathophysiology of cerebral
      malaria.

PMID- 22365904
TI  - FishPEST: an innovative software suite for fish parasitologists.

PMID- 22365905
TI  - The evolution of Trypanosoma cruzi: the 'bat seeding' hypothesis.
AB  - Recent discussions on the evolution of Trypanosoma cruzi have been dominated by
      the southern super-continent hypothesis, whereby T. cruzi and related parasites
      evolved in isolation in the mammals of South America, Antarctica and Australia.
      Here, we consider recent molecular evidence suggesting that T. cruzi evolved from
      within a broader clade of bat trypanosomes, and that bat trypanosomes have
      successfully made the switch into other mammalian hosts in both the New and Old
      Worlds. Accordingly, we propose an alternative hypothesis--the bat seeding
      hypothesis--whereby lineages of bat trypanosomes have switched into terrestrial
      mammals, thereby seeding the terrestrial lineages within the clade. One key
      implication of this finding is that T. cruzi may have evolved considerably more
      recently than previously envisaged.

PMID- 22365906
TI  - How ruminative thinking styles lead to dysfunctional cognitions: evidence from a
      mediation model.
AB  - BACKGROUND AND OBJECTIVES: Dysfunctional attitudes and a ruminative thinking
      style are of utmost clinical importance because they are found to be crucially
      implicated in depression vulnerability. In this study, based on the Diathesis
      Stress model (Beck, 1967) and the Differential Activation Hypothesis (Teasdale,
      1988), we investigated whether inter-individual differences in a ruminative
      thinking style would be related to the development of depressive symptoms,
      leading to the activation of dysfunctional attitudes under stress. METHODS:
      Seventy-six never depressed undergraduate students completed internet
      questionnaires measuring rumination, depressive symptoms and dysfunctional
      attitudes at 4 fixed moments in time (T1, T2, T3, T4): T1 was performed six weeks
      before their exams (considered as a low stress period); T2, T3 and T4 were
      performed during three consecutive weeks in their final exams (considered as life
      stress event). RESULTS: As expected, results revealed that the relationship
      between rumination, measured both out of (T1) and in (T2) a stressful period, and
      dysfunctional attitudes (measured at T4) was mediated by increased depressive
      symptoms (measured at T3). LIMITATIONS: Because the questionnaire for rumination
      was developed in the context of understanding responses to depressive symptoms,
      there might be a construct overlap between the predictor and the mediator of the
      models that were tested. Moreover, because only healthy undergraduates were
      included, our results demonstrate a decreased generalizability. CONCLUSIONS:
      These findings indicate that rumination can be conceived as a stable and
      underlying mechanism leading to depressed mood and dysfunctional attitudes under
      stress. Moreover, our findings highlight that clinical interventions should not
      only target dysfunctional schemas and attitudes, but might also benefit from the
      use of procedures aimed at changing processes such as a ruminative thinking
      style.

PMID- 22365907
TI  - Perceived control in clinically anxious and non-anxious children indirectly
      measured with the Implicit Association Procedure (IAP).
AB  - BACKGROUND: Perceived control is thought to play an important role in the
      development and maintenance of anxiety disorders in children. The objective of
      the present study was to further investigate the Perceived Control Implicit
      Association Procedure (IAP, Hogendoorn et al., 2008) as an indirect measure of
      perceived control in children. METHODS: The IAP was completed by 136 anxiety
      disordered children (aged 8-18 years old, M = 12.51) and 31 non-selected children
      (8-15 years old, M = 11.65). A second control group of 38 non-selected children
      (aged 8-18 years old, M = 12.08) was used to validate the pictorial stimuli in
      the computer task. RESULTS: First, children were able to correctly classify the
      pictures into Control and No control categories. Second, as predicted, anxious
      children reported less perceived control than the control group on both the
      direct measure (the ACQ-C) and the indirect measure (IAP). For the No Control
      score however, this was only the case for children younger than twelve years old.
      Third, test-retest correlation in the anxious group was fair to good (ICCs .57
      .58). CONCLUSIONS: These results suggest that the perceived control IAP is still
      quite experimental, but could be an interesting departure point for future
      research on perceived control in children.

PMID- 22365908
TI  - Hydration shells of molecules in molecular association: A mechanism for
      biomolecular recognition.
AB  - It has become clear that water should not be treated as an inert environment, but
      rather as an integral and active component of molecules. Here, we consider
      molecules and their hydration shells together as single entities. We show that:
      (1) the rate of association of molecules should be determined by the energetic
      barriers arising from interactions between their hydration shells; (2) replacing
      non-polar atoms of molecular surfaces with polar atoms increases these barriers;
      (3) reduction of the hydration shells during molecular association is the driving
      force for association not only of non-polar, but of polar molecules as well; (4)
      in most cases the dehydration of polar atoms during molecular association
      thermodynamically counteracts association; (5) on balance the thermodynamic
      stability of associated complexes is basically determined by the action of these
      two opposing factors: reduction of the hydration shells and dehydration of polar
      atoms; (6) molecular crowding reduces the energetic barriers counteracting
      association and changes the thermodynamic stability of associated complexes.
      These results lead to a mechanism for biomolecular recognition in the context of
      which the formation of unique structures is provided by rapidly forming kinetic
      traps with a biologically necessary lifetime but with a marginal thermodynamic
      stability. The mechanism gives definitive answers to questions concerning the
      heart of specific interactions between biomolecules, their folding and
      intracellular organization. Predictions are given that can be subjected to direct
      experimental tests.

PMID- 22365909
TI  - Physically based 3D finite element model of a single mineralized collagen
      microfibril.
AB  - Mineralized collagen microfibrils in human bone provide its mechanical properties
      (stiffness, elasticity, ductility, energy dissipation and strength). However,
      detailed 3D finite element models describing the mechanical behavior of the
      mineralized collagen microfibrils are still lacking. In the current work, we
      developed a 3D finite element model of the mineralized collagen microfibril that
      incorporates the physical 3D structural details. The model components consist of
      five tropocollagen molecules, mineral hydroxyapatite and intermolecular cross
      links joining primarily the ends of the tropocollagen molecules. Dimension,
      arrangement and mechanical behavior of the constituents are based on previously
      published experimental and theoretical data. Tensile and compressive loads were
      applied to the microfibril under different conditions (hydrated and dehydrated
      collagen) to investigate the relationship between the structure and the
      mechanical behavior of the mineralized collagen microfibril (stress-strain curve
      and elastic modulus). The computational results match the experimental available
      data well, and provide insight into the role of the phases and morphology on the
      microfibril behavior. Our predicted results show that the mechanical properties
      of collagen microfibrils arise due to their structure and properties. The
      proposed 3D finite element model of mineralized collagen microfibril contributes
      toward the investigation of the bottom-up structure-property relationships in
      human bone.

PMID- 22365910
TI  - Dietary iron supplements may affect stress adaptation and aggravate stress
      hyperglycemia in a rat model of psychological stress.
AB  - OBJECTIVE: Iron supplementation is believed to decrease the risk of iron
      deficiency anemia or low birth weight. In modern society, a majority of people
      are in a continual state of stress. Stress-induced hyperglycemia, known as
      transient hyperglycemia, may be a risk factor causing diabetes. To understand the
      role of iron in people under stress, it is necessary to evaluate the effect of
      iron supplementation on glucose or stress hyperglycemia. METHODS: The effect of a
      diet containing non-heme iron (80 or 320 mg/kg) on Sprague-Dawley rats and those
      under psychological stress was evaluated. RESULTS: Compared with control rats, a
      high-iron diet (320 mg/kg) increased blood glucose transiently in normal rats but
      induced hyperglycemia persistently in stressed rats throughout the experiment.
      Iron supplements further aggravated iron deposition and oxidative stress injury
      to the liver induced by the stress exposure. Glucose-related stress hormones were
      also affected by iron supplementation in stressed rats. CONCLUSION: Oxidative
      stress may be one of the main reasons for insulin resistance. Moreover, changes
      in stress hormones indicate that high-iron supplements may affect stress
      adaptation. Both are primary reasons for the hyperglycemia induced by iron
      supplementation in stressed rats. Gaining an insight into the mechanisms and
      correlations of these changes may be beneficial to human health and is important
      for the prevention of pathologic glycemia-related diseases.

PMID- 22365911
TI  - Synthesis and structure-activity relationship of 4-amino-2-phenylpyrimidine
      derivatives as a series of novel GPR119 agonists.
AB  - Through preparation and examination of a series of novel 4-amino-2
      phenylpyrimidine derivatives as agonists for GPR119, we identified 2-(4
      bromophenyl)-6-methyl-N-[2-(1-oxidopyridin-3-yl)ethyl]pyrimidin-4-amine (9t).
      Compound 9t improved glucose tolerance in mice following oral administration and
      showed good pharmacokinetic profiles in rats.

PMID- 22365912
TI  - New retinoid derivatives as back-ups of Adarotene.
AB  - Adarotene belongs to the so-called class of atypical retinoids. The presence of
      the phenolic hydroxyl group on Adarotene structure allows a rapid O
      glucuronidation as a major mechanism of elimination of the drug, favoring a fast
      excretion of its glucuronide metabolite in the urines. A series of ether,
      carbamate and ester derivatives was synthesized. All of them were studied and
      evaluated for their stability at different pH. The cytotoxic activity in vitro on
      NCI-H460 non-small cell lung carcinoma and A2780 ovarian tumor cell lines was
      also tested. A potential back-up of Adarotene has been selected to be evaluated
      in tumor models.

PMID- 22365913
TI  - Synthesis of macrocyclic bisbibenzyl derivatives and their anticancer effects as
      anti-tubulin agents.
AB  - Based on the core skeleton of the total synthesized bisbibenzyl marchantin C,
      riccardin D and plagiochin E, a series of brominated and aminomethylated
      derivatives of above three bisbibenzyls have been synthesized and their cytotoxic
      activity against KB, MCF-7 and PC3 cell lines has been preliminary evaluated. The
      bio-test results revealed that the brominated derivatives 21, 22, 24, 25 and 28
      exhibited excellent antiproliferative activity, with IC(50) value lower than
      their parent compounds. As a most potent microtubule depolymerization agent,
      compound 28 was found to arrest cells at the G(2)/M phase of the cell cycle as
      determined by the flow cytometry assay in PC3 cell line. The remarkable
      biological profile and novel structure of these bisbibenzyl derivatives make them
      possible as promising candidates for clinical development as chemotherapeutic
      agents.

PMID- 22365914
TI  - Changes by tacrolimus of the rat aortic proteome: involvement of endothelin-1.
AB  - The aim was to analyze the effect of tacrolimus on the aortic expression of
      proteins associated with the energetic metabolism and cytoskeleton and if it
      could be reverted by ET-1-receptor antagonist bosentan. Wistar Kyoto rats were
      divided into: control (n=10), tacrolimus (n=10, 0.5mg/kg bw/day tacrolimus for 30
      days) and tacrolimus+bosentan (n=10, 0.5mg/kg bw/day tacrolimus and 100mg/kg
      bw/day bosentan for 30 days). Rat aortic segments were homogenized and submitted
      to 2-dimensional electrophoresis and mass spectrometry. Tacrolimus treatment did
      not modify neither systolic nor diastolic arterial pressure but increased ET-1
      content, ET(A)- and ET(B)-type receptor expression in aorta. Proteomic study
      revealed that tacrolimus treatment modified the expression of aortic proteins
      associated with the cytoskeleton as some isotypes of lamin A and beta
      tropomyosin; and energetic metabolism such as ATP synthase gamma chain, NADH
      dehydrogenase ubiquinone, acyl CoA dehydrogenase long chain mitochondrial and
      phosphatidylinositol 3-kinase regulatory subunit gamma. Aortic expression of gp91
      phox and MnSOD was also increased by tacrolimus. Bosentan co-administration with
      tacrolimus prevented also changes in ET-1 content and the expression of proteins
      associated with energetic metabolism. Bosentan did not affect the increased
      expression of gp91-phox related to tacrolimus although significantly enhanced
      aortic MnSOD expression. As conclusion, tacrolimus treatment increased ET-1
      content in aortic wall and modified the expression of proteins associated with
      the cytoskeleton and energetic metabolism independently of changes on blood
      pressure. Bosentan reverted some effects induced by tacrolimus in the aorta and
      increased the antioxidant defense system.

PMID- 22365915
TI  - Laboratory-acquired brucellosis in Turkey.
AB  - BACKGROUND: Laboratory healthcare workers (HCWs) are at risk of laboratory
      acquired brucellosis (LAB). AIM: To describe the risk factors of LAB among HCWs.
      METHODS: A multicentre survey study was conducted by face-to-face interview in 38
      hospitals from 17 provinces of Turkey. A structured survey was administered to
      the HCWs, working in infectious diseases clinics and microbiology departments,
      who were at risk of brucella infection. FINDINGS: The survey response rate was
      100%. Of the 667 laboratory workers, 38 (5.8%) had a history of LAB. In
      multivariate analysis, factors independently associated with an increased risk of
      LAB included working with the brucella bacteria (odds ratio: 5.12; 95% confidence
      interval: 2.28-11.52; P < 0.001) and male gender (2.14; 1.02-4.45; P = 0.042).
      Using a biosafety cabinet level 2 (0.13; 0.03-0.60; P = 0.009), full adherence to
      glove use (0.27; 0.11-0.65; P = 0.004) and longer duration of professional life
      (0.86; 0.80-0.92; P < 0.001) were found to be protective. CONCLUSIONS: Working
      with the brucella bacteria, being male, a lack of compliance with personal
      protective equipment and biosafety cabinets were the independent risk factors for
      the development of LAB in our series. Increased adherence to personal protective
      equipment and use of biosafety cabinets should be priority targets to prevent
      LAB.

PMID- 22365916
TI  - Estimating bacterial surface contamination by means of ATP determinations: 20
      pence short of a pound.

PMID- 22365917
TI  - Hospital cleanliness: establishing a new science.

PMID- 22365918
TI  - Adaptive strategies for cumulative cultural learning.
AB  - The demographic and ecological success of our species is frequently attributed to
      our capacity for cumulative culture. However, it is not yet known how humans
      combine social and asocial learning to generate effective strategies for learning
      in a cumulative cultural context. Here we explore how cumulative culture
      influences the relative merits of various pure and conditional learning
      strategies, including pure asocial and social learning, critical social learning,
      conditional social learning and individual refiner strategies. We replicate the
      Rogers' paradox in the cumulative setting. However, our analysis suggests that
      strategies that resolved Rogers' paradox in a non-cumulative setting may not
      necessarily evolve in a cumulative setting, thus different strategies will
      optimize cumulative and non-cumulative cultural learning.

PMID- 22365919
TI  - Cullen's sign - Case report with a review of the literature.
AB  - INTRODUCTION: Cullen's sign is described as superficial oedema with bruising in
      the subcutaneous fatty tissue around the peri-umbilical region. It is also known
      as peri-umbilical ecchymosis. PRESENTATION OF CASE: We report a case of a fifty
      three year old gentleman who presented with non-specific abdominal pain.
      Significant bruising was present within the subcutaneous fatty tissue on the
      anterior abdominal wall in keeping with 'Cullen's sign.' Of note he denied any
      alcohol intake and his amylase was normal. A diagnosis of pancreatitis was made
      following a CT scan of his abdomen. DISCUSSION: A search of the entire English
      literature using PubMed with the phrase 'Cullen's sign' has been performed.
      Papers were reviewed in relation to recognition of this clinical sign,
      differential diagnosis, and management. CONCLUSION: Our case and review of the
      literature highlights the rarity of this clinical sign which a clinician may
      encounter. In addition we draw to attention the importance of having knowledge of
      the underlying possible conditions which may lead to this sign, and can be vital
      in successful acute management.

PMID- 22365920
TI  - Resection of metastatic liver cancer in a patient with a left-sided gallbladder
      and intrahepatic portal vein and bile duct anomalies: A case report.
AB  - INTRODUCTION: The presence of left-sided gallbladder is closely associated with
      multiple combined anomalies of the portal vein, hepatic vein, hepatic artery, and
      bile duct. This requires special attention for preoperative evaluation for the
      purpose of preventing postoperative complications. PRESENTATION OF CASE: A 70
      year-old woman with metastatic liver cancer and intrahepatic portal vein, biliary
      system and hepatic artery anomalies with left-sided gallbladder is reported. On
      computed tomography (CT), a solitary low density mass occupied from the right
      anterior to the posterior segment of the liver. The gallbladder bed was on the
      left of the hepatic fissure. On drip-infusion-cholangiography (DIC) CT three
      dimensional (3D) reconstruction, the left medial bile duct arose from the right
      umbilical portion after arising from the left lateral bile duct. Following a
      right hepatectomy and lymph node dissection of the hepatoduodenal ligament,
      hepaticojejunostomy was conducted separately to the left medial and left lateral
      bile duct. DISCUSSION: The left-sided gallbladder accompanies with several
      anomalies of hepatic vascular and bile duct anomalies in a frequent manner. A
      safe hepatectomy needs accurate operative plans to ascertain the range of
      hepatectomy, because it often has the diversity of a combined anomaly.
      CONCLUSION: Preoperative DIC-CT 3D reconstruction was extremely useful because it
      provided an important information that could not be obtained with 2D-DIC-CT. 3D
      imaging has the ability to demonstrate complex anatomical relationships, this
      devise is a effective new tool for making appropriate preoperative strategy.

PMID- 22365921
TI  - Glutamate and GABA synthesis, release, transport and metabolism as targets for
      seizure control.
AB  - The synthesis, release, reuptake, and metabolism of the excitatory and inhibitory
      neurotransmitters glutamate and GABA, respectively, are tightly controlled. Given
      the role that these two neurotransmitters play in normal and abnormal
      neurotransmission, it is important to consider the processes whereby they are
      regulated. This brief review is focused entirely on the metabolic aspects of
      glutamate and GABA synthesis and neurotransmission. It describes in limited
      detail the synthesis, release, reuptake, metabolism, cellular compartmentation
      and pharmacology of the glutamatergic and GABAergic synapse. This review also
      provides a summary and brief description of the pathologic and phenotypic
      features of the various genetic animal models that have been developed in an
      effort to provide a greater understanding of the role that each of the
      aforementioned metabolic processes plays in controlling excitatory and inhibitory
      neurotransmission and how their use will hopefully facilitate the development of
      safer and more efficacious therapies for the treatment of epilepsy and other
      neurological disorders.

PMID- 22365922
TI  - Interactions between the ROP18 kinase and host cell proteins that aid in the
      parasitism of Toxoplasma gondii.
AB  - Serine/threonine kinases secreted from rhoptry organelles are important virulence
      factors for Toxoplasma gondii. Among rhoptry proteins, the ROP18 kinase has been
      identified as a key virulence determinant mediating pathogenesis in T. gondii;
      however, the molecular mechanisms by which this kinase exerts its pathogenic
      action remain poorly understood. In this study, the interactions between the
      ROP18 kinase of Toxoplasma gondii and the host cell proteins were analyzed using
      a yeast two-hybrid technique. The cMyc-ROP18(25-251) fusion proteins expressed by
      pGBKT7 plasmids in AH109 yeast were bound to host cell proteins from a human
      fetal brain cDNA library transformed to AH109 yeast using a mating method. Using
      these selection procedures, we identified seven host proteins that had not
      previously been reported to interact with ROP18 such as DDB1, TOR1AIP1, integrin,
      SLC3A2, TPST2, DERL2 and OCIAD1. These host proteins are associated with DNA
      repair, transcriptional regulation, translation modification, protein degradation
      and cell adhesion. Our data strongly support the hypothesis that the secreted
      kinase ROP18 is involved in several complex cellular pathways for the invasion
      and commandeering of host functions.

PMID- 22365923
TI  - Sequential hermaphroditism and personality in a clonal vertebrate: the mangrove
      killifish.
AB  - Individuals are regularly documented to consistently differ in their behavioural
      types (BTs). For example, some individuals are bold whereas others are shy.
      Within the human personality literature, the big five personality dimensions are
      commonly documented to be sex-specific with testosterone suggested to underpin
      traits such as aggressiveness. In non-human animals recent research suggests sex
      specific BT expression may be influenced by ecology, mating system and sexual
      selection. While most research on sex-specific personality has focused on
      dioecious species, we explore sex differences in BT expression in a sequential
      hermaphrodite the mangrove killifish. We replicate within 7 isogenic genotypes
      and investigate sex differences (hermaphrodite and secondary male) in three BTs
      (exploration, boldness and aggression). This approach allows us to investigate
      sex differences in BT expression whilst controlling for genetic variation. In
      this study we find that both secondary males and hermaphrodites are repeatable at
      the individual level yet there was no difference between the sexes in average BT
      scores. Furthermore, aggression scores differed between genotypes, and were
      repeatable at the genotype level, suggesting strong genetic control. Finally,
      male boldness was significantly more repeatable than hermaphrodites potentially
      supporting recent proposals relating to sexual selection. We document a
      behavioural syndrome in male fish with bolder individuals being more aggressive,
      this behavioural syndrome was not observed however in hermaphrodites. In contrast
      to a previous developmental study in this species exploration did not correlate
      with either aggression or boldness in either males or hermaphrodites.

PMID- 22365924
TI  - orthodenticle/otx ortholog expression in the anterior brain and eyes of Sepia
      officinalis (Mollusca, Cephalopoda).
AB  - The origin of cerebral structures is a major issue in both developmental and
      evolutionary biology. Among Lophotrochozoans, cephalopods present both a derived
      nervous system and an original body plan, therefore they constitute a key model
      to study the evolution of nervous system and molecular processes that control the
      neural organization. We characterized a partial sequence of an ortholog of otx2
      in Sepia officinalis embryos, a gene specific to the anterior nervous system and
      eye development. By in situ hybridization, we assessed the expression pattern of
      otx2 during S. officinalis organogenesis and we showed that otx is expressed (1)
      in the eyes, from early to late developmental stages as observed in other species
      (2) in the nervous system during late developmental stages. The otx ortholog does
      not appear to be required for the precocious emergence of the nervous ganglia in
      cephalopods and is later expressed only in the most anterior ganglia of the
      future brain. Finally, otx expression becomes restricted to localized part of the
      brain, where it could be involved in the functional specification of the central
      nervous system of S. officinalis. These results suggest a conserved involvement
      of otx in eye maturation and development of the anterior neural structures in S.
      officinalis. 

PMID- 22365925
TI  - A prospective quality evaluation of single donor platelets (SDP) - an experience
      of a tertiary healthcare center in India.
AB  - Quality assurance of single donor platelets (SDP) is incomplete unless clinical
      response to platelet transfusion is measured. The primary objective of the study
      was to evaluate the quality of SDP derived from plateletpheresis procedures and
      to evaluate the response to platelet transfusion. Procedures were performed on
      2287 accepted donors while 271 donors were deferred. Platelet count <1.5 lac/MUl
      and hemoglobin <12.5 g/dl were the leading cause of deferral. The median platelet
      yield in a SDP bag was found to be 3.1*10(11). The median corrected count
      increment (CCI) and post-transfusion platelet recovery (PPR) were found to be
      10110*m(2)/MUl and 24.5%, respectively. In India, the criteria for the selection
      of plateletpheresis donors should be revisited. Based on quality parameters, the
      Fresenius COM.TEC cell separator is comparable to other cell separators.

PMID- 22365926
TI  - Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system - an
      update.
AB  - Considerable progress has been made in the last decade in producing purer, safer,
      leucocyte and plasma reduced platelet concentrates (PC) with an extended shelf
      life. The development of different pathogen inactivation technologies (PIT) has
      made a substantial contribution to this trend. Preceding platelet PIT (INTERCEPT
      Blood System/Cerus Corporation, Concord, CA, USA; MIRASOL/Caridian BCT, Lakewood,
      CO, USA) are based on adding a photosensitive compound to PC. The mixture is then
      activated by UV light in the UVB and/or UVA spectral regions. A novel procedure,
      THERAFLEX UV-Platelets (MacoPharma, Mouvaux, France), was recently developed that
      uses short-wave ultraviolet light (UVC), without addition of any photoactive
      agent. This technology has proven to be highly effective in sterilising bacteria
      (the major cause of morbidity/mortality after platelet transfusion) as well as
      inactivating other transfusion transmitted DNA/RNA containing pathogens and
      residual leucocytes. Any PIT reflects a balance between the efficacy of pathogen
      inactivation and preservation of platelet quality and function. A broad spectrum
      of in vitro tests have become available for the assessment of platelet storage
      lesion (PSL), aiming to better predict clinical outcome and untoward effects of
      platelet therapy. Recent paired studies on the release of platelet-derived
      cytokines, as new platelet performance indicators, revealed a parallel increase
      in both THERAFLEX UV-treated and control PC throughout storage, supporting the
      notion that the bioavailability of platelet function is not grossly affected by
      UVC treatment. This is corroborated by some newer technologies for proteomic
      analysis, showing that the THERAFLEX UV-Platelets system results in limited
      disruption of integrin-regulating extracellular disulfide bonds and minimal
      protein alterations when compared to UVB and gamma irradiation. Moreover,
      standard in vitro parameters reflecting activation, metabolic activity and
      function of platelets are useful indicators of the overall performance of
      processing and storage and may be used as surrogate markers of platelet quality
      in vivo. However, there is some doubt as to what degree each marker alone or in
      combination reflects the true clinical outcome of transfused platelets.
      Therefore, an appropriate clinical programme has been initiated. The preclinical
      evaluation demonstrated tolerability and immunological safety of THERAFLEX UV
      Platelets using an animal model. Additionally, the system has successfully
      completed two autologous Phase I trials on recovery and survival. Preliminary
      results suggest that the recovery and survival rates are consistent with other
      pathogen reduced platelet products that are licensed and in use. The method is
      currently under evaluation for safety and tolerability of UVC-treated platelets
      in healthy volunteers. Presently the THERAFLEX UV-Platelets system is the
      simplest and purest PIT easily adaptable to the existing blood bank setting. In
      the future, extension of the application range of the THERAFLEX UV-Platelets
      system is expected, in order to make this new technology compatible with a broad
      spectrum of collection and processing platforms, and with other blood products.

PMID- 22365927
TI  - Singlet oxygen and non-photochemical quenching contribute to oxidation of the
      plastoquinone-pool under high light stress in Arabidopsis.
AB  - The redox state of plastoquinone-pool in chloroplasts is crucial for driving many
      responses to variable environment, from short-term effects to those at the gene
      expression level. In the present studies, we showed for the first time that the
      plastoquinone-pool undergoes relatively fast oxidation during high light stress
      of low light-grown Arabidopsis plants. This oxidation was not caused by
      photoinhibition of photosystem II, but mainly by singlet oxygen generated in
      photosystem II and non-photochemical quenching in light harvesting complex
      antenna of the photosystem, as revealed in experiments with a singlet oxygen
      scavenger and with Arabidopsis npq4 mutant. The latter mechanism suppresses the
      influx of electrons to the plastoquinone-pool preventing its excessive reduction.
      The obtained results are of crucial importance in light of the function of the
      redox state of the plastoquinone-pool in triggering many high light-stimulated
      physiological responses of plants.

PMID- 22365928
TI  - The site-directed mutation I(L177)H in Rhodobacter sphaeroides reaction center
      affects coordination of P(A) and B(B) bacteriochlorophylls.
AB  - To explore the influence of the I(L177)H single mutation on the properties of the
      nearest bacteriochlorophylls (BChls), three reaction centers (RCs) bearing double
      mutations were constructed in the photosynthetic purple bacterium Rhodobacter
      sphaeroides, and their properties and pigment content were compared with those of
      the correspondent single mutant RCs. Each pair of the mutations comprised the
      amino acid substitution I(L177)H and another mutation altering histidine ligand
      of BChl P(A) or BChl B(B). Contrary to expectations, the double mutation
      I(L177)H+H(L173)L does not bring about a heterodimer RC but causes a 46nm blue
      shift of the long-wavelength P absorbance band. The histidine L177 or a water
      molecule were suggested as putative ligands for P(A) in the RC I(L177)H+H(L173)L
      although this would imply a reorientation of the His backbone and additional
      rearrangements in the primary donor environment or even a repositioning of the
      BChl dimer. The crystal structure of the mutant I(L177)H reaction center
      determined to a resolution of 2.9A shows changes at the interface region between
      the BChl P(A) and the monomeric BChl B(B). Spectral and pigment analysis provided
      evidence for beta-coordination of the BChl B(B) in the double mutant RC
      I(L177)H+H(M182)L and for its hexacoordination in the mutant reaction center
      I(L177)H. Computer modeling suggests involvement of two water molecules in the
      beta-coordination of the BChl B(B). Possible structural consequences of the L177
      mutation affecting the coordination of the two BChls P(A) and B(B) are discussed.
      This article is part of a Special Issue entitled: Photosynthesis Research for
      Sustainability: from Natural to Artificial.

PMID- 22365929
TI  - Identification by site-directed mutagenesis of a hydrophobic binding site of the
      mitochondrial carnitine/acylcarnitine carrier involved in the interaction with
      acyl groups.
AB  - The role of hydrophobic residues of the mitochondrial carnitine/acylcarnitine
      carrier (CAC) in the inhibition by acylcarnitines has been investigated by site
      directed mutagenesis. According to the homology model of CAC in cytosolic opened
      conformation (c-state), L14, G17, G21, V25, P78, V82, M85, C89, F93, A276, A279,
      C283, F287 are located in the 1st (H1), 2nd (H2) and 6th (H6) transmembrane alpha
      helices and exposed in the central cavity, forming a hydrophobic half shell.
      These residues have been substituted with A (or G) and in some cases with M.
      Mutants have been assayed for transport activity measured as
      [(3)H]carnitine/carnitine antiport in proteoliposomes. With the exception of G17A
      and G21M, mutants exhibited activity from 20% to 100% of WT. Among the active
      mutants only G21A, V25M, P78A and P78M showed Vmax lower than half and/or Km more
      than two fold respect to WT. Acylcarnitines competitively inhibited carnitine
      antiport. The extent of inhibition of the mutants by acylcarnitines with acyl
      chain length of 2, 4, 8, 12, 14 and 16 has been compared with the WT. V25A, P78A,
      P78M and A279G showed reduced extent of inhibition by all the acylcarnitines;
      V25M showed reduced inhibition by shorter acylcarnitines; V82A, V82M, M85A, C89A
      and A276G showed reduced inhibition by longer acylcarnitines, respect to WT.
      C283A showed increased extent of inhibition by acylcarnitines. Variations of Ki
      of mutants for acylcarnitines reflected variations of the inhibition profiles.
      The data demonstrated that V25, P78, V82, M85 and C89 are involved in the acyl
      chain binding to the CAC in c-state.

PMID- 22365930
TI  - An investigation into a cardiolipin acyl chain insertion site in cytochrome c.
AB  - Mitochondrial cytochrome c associates with the phosphoplipid cardiolipin (CL)
      through a combination of electrostatic and hydrophobic interactions. The latter
      occurs by insertion into cytochrome c of an acyl chain, resulting in the
      dissociation of the axial Met-80 heme-iron ligand. The resulting five coordinate
      cytochrome c/CL complex has peroxidatic properties leading to peroxidation of CL
      and dissociation of the complex. These events are considered to be pre-apoptotic
      and culminate with release of cytochrome c from the mitochondria into the
      cytoplasm. Two distinct surface regions on cytochrome c have been suggested to
      mediate CL acyl chain insertion and this study has probed one of these regions.
      We have constructed a series of alanine mutants aimed at disrupting a surface
      cleft formed between residues 67-71 and 82-85. The physicochemical properties,
      peroxidase activity, CL binding, and kinetics of carbon monoxide (CO) binding to
      the ferrous cytochrome c/CL complex have been assessed for the individual
      mutants. Our findings reveal that the majority of mutants are capable of binding
      CL in the same apparent stoichiometry as the wild-type protein, with the extent
      to which the Met-80 ligand is bound in the ferrous cytochrome c/CL complex being
      mutant specific at neutral pH. Mutation of the species conserved Arg-91 residue,
      that anchors the cleft, results in the greatest changes to physicochemical
      properties of the protein leading to a change in the CL binding ratio required to
      effect structural changes and to the ligand-exchange properties of the ferrous
      cytochrome c/CL complex.

PMID- 22365931
TI  - Alterations in photosynthetic pigments and amino acid composition of D1 protein
      change energy distribution in photosystem II.
AB  - The marine cyanobacterium Prochlorococcus marinus accumulates divinyl
      chlorophylls instead of monovinyl chlorophylls to harvest light energy. As well
      as this difference in its chromophore composition, some amino acid residues in
      its photosystem II D1 protein were different from the conserved amino acid
      residues in other photosynthetic organisms. We examined PSII complexes isolated
      from mutants of Synechocystis sp. PCC 6803, in which chromophore and D1 protein
      were altered (Hisashi Ito and Ayumi Tanaka, 2011) to clarify the effects of
      chromophores/D1 protein composition on the excitation energy distribution. We
      prepared the mutants accumulating divinyl chlorophyll (DV mutant). The amino acid
      residues of V205 and G282 in the D1 protein were substituted with M205 and C282
      in the DV mutant to mimic Prochlorococcus D1 protein (DV-V205M/G282C mutant).
      Isolated PSII complexes were analyzed by time-resolved fluorescence spectroscopy.
      Energy transfer in CP47 was interrupted in PSII containing divinyl chlorophylls.
      The V205M/G282C mutation did not recover the energy transfer pathway in CP47,
      instead, the mutation allowed the excitation energy transfer from CP43 to CP47,
      which neighbors in the PSII dimer. Mutual orientation of the subcomplexes of PSII
      might be affected by the substitution. The changes of the energy transfer
      pathways would reduce energy transfer from antennae to the PSII reaction center,
      and allow Prochlorococcus to acquire light tolerance.

PMID- 22365932
TI  - Thermodynamic characterization of viral procapsid expansion into a functional
      capsid shell.
AB  - The assembly of "complex" DNA viruses such as the herpesviruses and many tailed
      bacteriophages includes a DNA packaging step where the viral genome is inserted
      into a preformed procapsid shell. Packaging triggers a remarkable capsid
      expansion transition that results in thinning of the shell and an increase in
      capsid volume to accept the full-length genome. This transition is considered
      irreversible; however, here we demonstrate that the phage lambda procapsid can be
      expanded with urea in vitro and that the transition is fully reversible. This
      provides an unprecedented opportunity to evaluate the thermodynamic features of
      this fascinating and essential step in virus assembly. We show that urea
      triggered expansion is highly cooperative and strongly temperature dependent.
      Thermodynamic analysis indicates that the free energy of expansion is influenced
      by magnesium concentration (3-13 kcal/mol in the presence of 0.2-10 mM Mg(2+))
      and that significant hydrophobic surface area is exposed in the expanded shell.
      Conversely, Mg(2+) drives the expanded shell back to the procapsid conformation
      in a highly cooperative transition that is also temperature dependent and
      strongly influenced by urea. We demonstrate that the gpD decoration protein adds
      to the urea-expanded capsid, presumably at hydrophobic patches exposed at the 3
      fold axes of the expanded capsid lattice. The decorated capsid is biologically
      active and sponsors packaging of the viral genome in vitro. The roles of divalent
      metal and hydrophobic interactions in controlling packaging-triggered expansion
      of the procapsid shell are discussed in relation to a general mechanism for DNA
      triggered procapsid expansion in the complex double-stranded DNA viruses.

PMID- 22365933
TI  - The role of the beta5-alpha11 loop in the active-site dynamics of acylated
      penicillin-binding protein A from Mycobacterium tuberculosis.
AB  - Penicillin-binding protein A (PBPA) is a class B penicillin-binding protein that
      is important for cell division in Mycobacterium tuberculosis. We have determined
      a second crystal structure of PBPA in apo form and compared it with an earlier
      structure of apoenzyme. Significant structural differences in the active site
      region are apparent, including increased ordering of a beta-hairpin loop and a
      shift of the SxN active site motif such that it now occupies a position that
      appears catalytically competent. Using two assays, including one that uses the
      intrinsic fluorescence of a tryptophan residue, we have also measured the second
      order acylation rate constants for the antibiotics imipenem, penicillin G, and
      ceftriaxone. Of these, imipenem, which has demonstrable anti-tubercular activity,
      shows the highest acylation efficiency. Crystal structures of PBPA in complex
      with the same antibiotics were also determined, and all show conformational
      differences in the beta5-alpha11 loop near the active site, but these differ for
      each beta-lactam and also for each of the two molecules in the crystallographic
      asymmetric unit. Overall, these data reveal the beta5-alpha11 loop of PBPA as a
      flexible region that appears important for acylation and provide further evidence
      that penicillin-binding proteins in apo form can occupy different conformational
      states.

PMID- 22365934
TI  - Further insights into the properties of the HIV gp41 fusion domain: commentary on
      the article by A. L. Lai et al.

PMID- 22365935
TI  - A photovoice documentation of the role of neighborhood physical and social
      environments in older adults' physical activity in two metropolitan areas in
      North America.
AB  - A substantial body of evidence indicates that regular engagement in moderate
      intensity physical activity on most days of the week is sufficient for older
      adults to achieve positive health outcomes. Although there is a growing body of
      literature that examines the affect of neighborhood environment on physical
      activity in older adults, the research tends to overlook social aspects that
      potentially shape the relationship between physical environment and physical
      activity. This article presents qualitative themes related to the role of the
      physical and social environments in influencing physical activity among older
      adults as identified through the photovoice method with sixty-six older adults in
      eight neighborhoods in metropolitan Vancouver, British Columbia, Canada and
      Greater Portland, Oregon, USA. The photovoice data generated seven themes: being
      safe and feeling secure, getting there, comfort in movement, diversity of
      destinations, community-based programs, peer support and
      intergenerational/volunteer activities. Although the majority of these themes
      have explicit or implicit physical and social aspects, certain themes are
      primarily based on physical environmental aspects (e.g., safe and feeling secure,
      comfort in movement), while a few themes are more oriented to social context
      (e.g., peer support, intergenerational activity/volunteering). The themes are
      discussed with a focus on how the neighborhood physical and social environmental
      aspects interplay to foster or hinder older adults in staying active in both
      everyday activities and intentional physical activities. Policy implications of
      the findings are discussed.

PMID- 22365936
TI  - The influence of cognitive-perceptual variables on patterns of change over time
      in rural midlife and older women's healthy eating.
AB  - Although studies demonstrate that dietary interventions for healthy adults can
      result in beneficial dietary changes, few studies examine when and how people
      change in response to these interventions, particularly in rural populations. The
      purpose of this study was to examine patterns of change over time in healthy
      eating behaviors in midlife and older women in response to a one-year health
      promoting intervention, and to examine what predictors (perceived benefits,
      barriers, self-efficacy, and family support for healthy eating) influence the
      changes during the intervention and follow-up. Data for this secondary analysis
      were from the Wellness for Women community-based trial. Women (N = 225) between
      the ages of 50-69 in rural Nebraska, U.S.A., were recruited. A repeated-measures
      experimental design was used with randomization of two rural counties to
      intervention (tailored newsletter) or comparison (standard newsletter) groups.
      Eating behavior was measured by the Healthy Eating Index. The predictor variables
      were assessed using standard measures. Data analysis was done using latent growth
      curve modeling. The tailored newsletter group was successful in improving their
      healthy eating behavior compared to the standard newsletter group during the one
      year intervention, at the end of the intervention, and during the follow-up
      phase. Family support at the end of the intervention was positively associated
      with healthy eating at the end of the intervention. Perceived barriers had the
      strongest impact on healthy eating behavior at all time points. Compared to
      participants in the standard newsletter group, those in the tailored newsletter
      group perceived more family support and fewer barriers for healthy eating at the
      end of the intervention (mediation effects). Based on these findings, both family
      support and perceived barriers should be central components of interventions
      focused on healthy eating behavior in rural midlife and older women.

PMID- 22365937
TI  - The journals are full of great studies but can we believe the statistics?
      Revisiting the mass privatisation - mortality debate.
AB  - Cross-national statistical analyses based on country-level panel data are
      increasingly popular in social epidemiology. To provide reliable results on the
      societal determinants of health, analysts must give very careful consideration to
      conceptual and methodological issues: aggregate (historical) data are typically
      compatible with multiple alternative stories of the data-generating process.
      Studies in this field which fail to relate their empirical approach to the true
      underlying data-generating process are likely to produce misleading results if,
      for example, they misspecify their models by failing to explore the statistical
      properties of the longitudinal aspect of their data or by ignoring endogeneity
      issues. We illustrate the importance of this extra need for care with reference
      to a recent debate on whether discussing the role of rapid mass privatisation can
      explain post-communist mortality fluctuations. We demonstrate that the finding
      that rapid mass privatisation was a "crucial determinant" of male mortality
      fluctuations in the post-communist world is rejected once better consideration is
      given to the way in which the data are generated.

PMID- 22365938
TI  - Are recessions really good for your health? Evidence from Canada.
AB  - This study investigates the relationship between business cycle fluctuations and
      health in the Canadian context, given that a procyclical relationship between
      mortality rates and unemployment rates has already been well established in the
      U.S. literature. Using a fixed effects model and provincial data over the period
      1977-2009, we estimate the effect of unemployment rates on Canadian age and
      gender specific mortality rates. Consistent with U.S. results, there is some
      evidence of a strong procyclical pattern in the mortality rates of middle-aged
      Canadians. We find that a one percentage point increase in the unemployment rate
      lowers the predicted mortality rate of individuals in their 30s by nearly 2
      percent. In contrast to the U.S. data, we do not find a significant cyclical
      pattern in the mortality rates of infants and seniors.

PMID- 22365939
TI  - Do neighborhoods affect individual mortality? A systematic review and meta
      analysis of multilevel studies.
AB  - There has been increasing interest in investigating whether inhabitants in
      socially or physically deprived neighborhoods have higher mortality when
      individual socioeconomic status is adjusted for. Results so far appear ambiguous
      and the objective of this study was to conduct a systematic literature review of
      previous studies and to quantify the association between area-level socioeconomic
      status (ALSES) and all-cause mortality in a meta-analysis. Current guidelines for
      systematic reviews and meta-analyses were followed. Articles were retrieved from
      Medline, Embase, Social Sciences Citation Index and PsycInfo and individually
      evaluated by two researchers. Only peer-reviewed multilevel studies from high
      income countries, which analyzed the influence of at least one area-level
      indicator and which controlled for individual SES, were included. The ALSES
      estimates in each study were first combined into a single estimate using weighted
      linear regression. In the meta-analysis we calculated combined estimates with
      random effects to account for heterogeneity between studies. Out of the 40
      studies found eligible for the systematic review 18 studies were included in the
      meta-analysis. The systematic review suggests that there is an association
      between social cohesion and mortality but found no evidence for a clear
      association for area-level income inequality or for social capital. Studies
      including more than one area level suggest that characteristics on different area
      levels contribute to individual mortality. In the meta-analysis we found
      significantly higher mortality among inhabitants living in areas with low ALSES.
      Associations were stronger for men and younger age groups and in studies
      analyzing geographical units with fewer inhabitants.

PMID- 22365940
TI  - Decreased births among black female adolescents following school desegregation.
AB  - Although the socioeconomic impact of school desegregation in the U.S. has been
      well documented, little is known about the health consequences of this policy.
      The purpose of this study was to quantify the associations between school
      desegregation and adolescent births among black and white females. We compared
      the change in prevalence of adolescent births in areas that implemented school
      desegregation plans in the 1970s with areas that implemented school desegregation
      plans in other decades, using difference-in-difference methods with 1970 and 1980
      Census microdata. School desegregation policy in the U.S. in the 1970s was
      associated with a significant reduction of 3.2 percentage points in the
      prevalence of births among black female adolescents between 1970 and 1980. This
      association was specific to black female adolescents and was not observed among
      white adolescents.

PMID- 22365941
TI  - Successful treatment sequence incorporating bevacizumab for therapy of
      polyneuropathy in two patients with POEMS syndrome.

PMID- 22365942
TI  - A new recurrent chromosomal translocation t(3;11)(q13;q14) in myelodysplastic
      syndromes associated with overexpression of the ILDR1 gene.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases
      characterized by ineffective hematopoiesis and an increased risk of evolution to
      acute myeloid leukemia (AML). In this study, the combination of conventional
      cytogenetic, FISH studies and molecular techniques allowed us to unveil a novel
      recurrent t(3;11)(q13;q14) causing the overexpression of the immunoglobulin-like
      domain-containing receptor (ILDR1) gene. The analysis of gene expression was
      extended to Refractory Anemia (RA) and Refractory Anemia with excess blasts
      (RAEB) cases revealing ILDR1 overexpression in 36% of RAEB subgroup. The
      biological implications of the ILDR1 overexpression in MDS pathogenesis and its
      potential prognostic significance should be further investigated.

PMID- 22365944
TI  - 790 Kb microduplication in chromosome band 17p13.1 associated with intellectual
      disability, afebrile seizures, dysmorphic features, diabetes, and hypothyroidism.
AB  - We report a patient with a moderate mental retardation, afebrile seizure, mild
      dysmorphic features and type 2 diabetes mellitus with mild obesity and metabolic
      syndrome. Array-CGH analysis revealed a de novo 790-830 kb duplication on
      chromosome 17p13.1, not reported so far. Among the approximately 50 genes
      involved in the rearrangement, neuroligin 2 (NLGN2) and ephrin B3 (EFNB3) are
      candidates for the mental retardation phenotype. NLGN2 may therefore be a novel
      candidate gene for mental retardation or autistic spectrum disorder, joining
      other members of the neurexin/neuroligin network. Moreover, GLUT4, a member of
      the solute carrier family 2, may play a role in the patient's type 2 diabetes.

PMID- 22365943
TI  - De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A
      and B genes in a male infant with episodic hypotonia: a genomics approach to
      personalized medicine.
AB  - Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating
      neurotransmitters and various other biogenic amines. Patients deficient in one or
      both enzymes have distinct metabolic and neurologic profiles. MAOB deficient
      patients exhibit normal clinical characteristics and behavior, while MAOA
      deficient patients have borderline intellectual deficiency and impaired impulse
      control. Patients who lack both MAOA and MAOB have the most extreme laboratory
      values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O
      methylated amine metabolites and reduced deaminated metabolites) in addition to
      severe intellectual deficiency and behavioral problems. Mice lacking maoa and
      moab exhibit decreased proliferation of neural stem cells beginning in late
      gestation and persisting into adulthood. These mice show significantly increased
      monoamine levels, particularly serotonin, as well as anxiety-like behaviors as
      adults, suggesting that brain maturation in late embryonic development is
      adversely affected by elevated serotonin levels. We report the case of a male
      infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and
      MAOB genes. This newly recognized X-linked disorder is characterized by severe
      intellectual disability and unusual episodes of hypotonia, which resemble atonic
      seizures, but have no EEG correlate. A customized low dietary amine diet was
      implemented in an attempt to prevent the cardiovascular complications that can
      result from the excessive intake of these compounds. This is the second report of
      this deletion and the first attempt to maintain the patient's cardiovascular
      health through dietary manipulation. Even though a diet low in tyramine,
      phenylethylamine, and dopa/dopamine is necessary for long-term management, it
      will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB
      deficiency. Our patient displays markedly elevated levels of serotonin in blood,
      serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like
      para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower
      serotonin levels in patients with absent monoamine oxidase enzymes.

PMID- 22365945
TI  - A role for solvents in the toxicity of agricultural organophosphorus pesticides.
AB  - Organophosphorus (OP) insecticide self-poisoning is responsible for about one
      quarter of global suicides. Treatment focuses on the fact that OP compounds
      inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not
      benefit poisoned humans. We therefore studied the role of solvent coformulants in
      OP toxicity in a novel minipig model of agricultural OP poisoning. Gottingen
      minipigs were orally poisoned with clinically relevant doses of agricultural
      emulsifiable concentrate (EC) dimethoate, dimethoate active ingredient (AI)
      alone, or solvents. Cardiorespiratory physiology and neuromuscular (NMJ)
      function, blood AChE activity, and arterial lactate concentration were monitored
      for 12h to assess poisoning severity. Poisoning with agricultural dimethoate
      EC40, but not saline, caused respiratory arrest within 30 min, severe
      distributive shock and NMJ dysfunction, that was similar to human poisoning. Mean
      arterial lactate rose to 15.6 [SD 2.8] mM in poisoned pigs compared to 1.4 [0.4]
      in controls. Moderate toxicity resulted from poisoning with dimethoate AI alone,
      or the major solvent cyclohexanone. Combining dimethoate with cyclohexanone
      reproduced severe poisoning characteristic of agricultural dimethoate EC
      poisoning. A formulation without cyclohexanone showed less mammalian toxicity.
      These results indicate that solvents play a crucial role in dimethoate toxicity.
      Regulatory assessment of pesticide toxicity should include solvents as well as
      the AIs which currently dominate the assessment. Reformulation of OP insecticides
      to ensure that the agricultural product has lower mammalian toxicity could result
      in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates.

PMID- 22365946
TI  - Intermittent infusions of carperitide or inotoropes in out-patients with advanced
      heart failure.
AB  - BACKGROUND: The ambulatory treatment of advanced heart failure (HF) with
      intermittent infusions of inotropes or natriuretic peptide chosen immediately
      before each infusion has not been described. METHODS: Between May 2005 and July
      2009, we treated 11 patients presenting with advanced HF, who received a total of
      369 infusions of carperitide, olprinone, dopamine, or dobutamine, once or twice
      weekly. The pharmaceutical was selected before each infusion based on the
      systolic blood pressure (BP). RESULTS: Carperitide, olprinone, and catecholamines
      were administered to 8 (73 infusions of 0.030+/-0.004MUg/kg/min for 3.3+/-0.8h),
      4 (18 infusions of 0.070+/-0.017MUg/kg/min for 3.3+/-0.5h), and 6 patients (278
      infusions of 3.6+/-1.9MUg/kg/min for 2.8+/-1.0h), respectively. No adverse effect
      requiring cessation of infusion was observed. Over a mean follow-up of 29.3+/
      28.8months (range 2-104), 4 patients died, all from cardiac causes. The Kaplan
      Meier cumulative survival rate was 69.3% at 20 months (median follow-up).
      Compared with the pre-infusion period, the duration and number of
      hospitalizations for management of HF were decreased by 73.9% (p=0.017), and
      51.9% (p=0.007), respectively, during the treatment period, and the overall
      medical costs by 56.9% (p=0.021). CONCLUSIONS: In this study population,
      intermittent drug infusions selected from inotropes or natriuretic peptide based
      on the baseline systolic BP significantly decreased the length and number of
      hospitalizations and costs, without increasing mortality. These results indicate
      that intermittent infusions might be one of the therapeutic options in advanced
      HF.

PMID- 22365947
TI  - Comparative study of therapeutic effects of short- and long-acting loop diuretics
      in outpatients with chronic heart failure (COLD-CHF).
AB  - BACKGROUND: Loop diuretics have two different classes with different duration of
      activity: short-acting such as furosemide (duration of activity, 6h) and long
      acting such as azosemide (duration of activity, 10-12h). We conducted a
      multicenter, randomized, controlled trial in order to compare the therapeutic
      effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting
      one, on neurohumoral factors and cardiac function in outpatients with chronic
      heart failure (CHF). METHODS: We enrolled 98 patients with CHF who were receiving
      furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly
      divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group
      continued furosemide at the same dosage, and the azosemide group switched from
      furosemide to azosemide. At baseline and after 3 months, we measured body weight,
      and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP),
      norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium,
      and hematocrit. Chest X-ray and echocardiography were also performed. RESULTS:
      Body weight and plasma levels of BNP and ANP significantly decreased after 3
      months in the azosemide group compared to the furosemide group. There were no
      significant differences in changes of levels of creatinine, blood urea nitrogen,
      sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months
      between the furosemide and azosemide groups. Echocardiography and chest X-ray did
      not demonstrate significant differences between the two groups. CONCLUSIONS: Long
      acting azosemide is suggested to be useful for the improvement of neurohumoral
      factors compared with short-acting furosemide in patients with CHF.

PMID- 22365948
TI  - High-mobility group box 1 protein blockade suppresses development of abdominal
      aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) expansion is characterized by chronic
      inflammatory cell infiltration and extracellular matrix degradation. High
      mobility group box 1 protein (HMGB1) is one of the damage-associated molecular
      pattern molecules derived from injured/necrotic and activated inflammatory cells.
      We investigated the expression of HMGB1 in human AAA and mouse experimental AAA.
      Then, we evaluated the effect of HMGB1 blockade on AAA formation in the mouse
      model. METHODS AND RESULTS: Human AAA samples showed increased HMGB1 expression
      compared with normal aortic wall. In a mouse CaCl(2)-induced AAA model, the
      expression of HMGB1 was increased compared with that in sham, and was positively
      correlated with matrix metalloproteinase (MMP)-2 and MMP-9 activity. We
      administered neutralizing anti-HMGB1 antibody (AAA/anti-H) or control antibody
      (AAA/C) to AAA mice subcutaneously every 3 days for 6 weeks. Treatment with
      neutralizing anti-HMGB1 antibody suppressed AAA formation, and attenuated elastin
      fragmentation. HMGB1 blockade markedly reduced the number of macrophages and MMP
      2 and MMP-9 activity in aneurysmal tissue. The mRNA level of tumor necrosis
      factor-alpha and CD68 in the aorta was reduced in AAA/anti-H compared with AAA/C.
      CONCLUSIONS: Elevation of HMGB1 level in aneurysmal tissue was observed in human
      AAA and mouse experimental AAA. HMGB1 blockade in a mouse AAA model reduced AAA
      progression, in association with reduced infiltration of macrophages and MMPs
      activity. These findings suggest a significant role for HMGB1 in the pathogenesis
      of AAA.

PMID- 22365949
TI  - Serum deoxyribonuclease I activity can be a useful diagnostic marker for the
      early diagnosis of unstable angina pectoris or non-ST-segment elevation
      myocardial infarction.
AB  - BACKGROUND AND PURPOSE: Recently, serum deoxyribonuclease I (DNase I) activity
      has been highlighted as a potential diagnostic marker for transient myocardial
      ischemia. To evaluate whether serum DNase I activity can be a useful biomarker
      for diagnosing unstable angina pectoris (UAP) or non-ST-segment elevation
      myocardial infarction (NSTEMI), we investigated serial changes in DNase I levels
      after chest pain in UAP and NSTEMI (UAP/NSTEMI) patients. METHODS AND RESULTS:
      Thirty-three and ten patients classified into the UAP/NSTEMI and the chest pain
      syndrome (CPS) group, respectively, were enrolled. The serum DNase I activity
      levels within 3h after chest pain and the absolute median value of percentage
      differences in serum DNase I activity levels from admission to 3h after
      hospitalization in the UAP/NSTEMI patients was significantly higher than those in
      the CPS patients. We evaluated the patients to show positive results for DNase I
      activity if the serum levels or percentage differences exceeded the corresponding
      cut-off values. The sensitivity and specificity of DNase I within 6h after chest
      pain in the UAP/NSTEMI patients without elevated levels of cardiac troponin T and
      the MB isoenzyme of creatine kinase were 89% and 88%, respectively. CONCLUSIONS:
      Serum DNase I activity can be a useful marker for the early diagnosis of
      UAP/NSTEMI after the onset of chest pain, irrespective of the evidence of
      myocardial injury.

PMID- 22365951
TI  - Functional structure of antennal sensilla in the myrmecophilous beetle Paussus
      favieri (Coleoptera, Carabidae, Paussini).
AB  - The evolution of a myrmecophilous lifestyle in beetles is often associated with
      morphological alterations. In particular, the antennae of all members of the
      myrmecophilous ground beetle tribe Paussini are greatly modified, with
      flagellomeres flattened or crassate, frequently reduced in number from 9 to 5 or
      even 1 single "antennal club". The enhanced glandular function of the antennal
      club has been recently described by scanning (SEM) and transmission (TEM)
      electron microscopy in Paussus favieri Fairmaire, 1851, where the antenna has
      become a complex glandular organ, supplying rewarding substances to the ants. In
      the present work, the antennal sensilla of P. favieri are investigated by SEM,
      TEM and focused ion beam (FIB/SEM) technology. Most sensilla of scape and
      antennal club are highly modified mechanoreceptors (i.e. multipointed, fringed,
      branched, brush-like, sickle-shaped), singly or grouped in tufts ("antennal
      symphilous organs"). These "trichomes", here assigned to 8 different morphotypes
      of sensilla chaetica (Ch.1-Ch.8), show a variable number of basal pores (present
      also at the base of the taste sensilla Ch.9), which spread dense substances of
      unknown chemical composition on the seta. Although hygro-, thermo- and
      chemoreceptors are reduced in number as compared with non-myrmecophilous
      relatives, and mainly relegated to the apex of the antennal club, their diversity
      is comparable to that of other carabid beetles: two types of sensilla trichodea
      (Tr.1-Tr.2); three types of basiconica (Ba.1-Ba.3); one type of campaniformia
      (Ca); one type of coeloconica (Co) and one type of Bohm sensilla (Bo). Contrary
      to the hypothesis that Paussus species lack a Johston's organ, a non-connective
      chordotonal organ composed of 9 groups of scolopidia has been found inside the
      pedicel. A comparison between sensilla of P. favieri and those of other non
      myrmecophilous and myrmecophilous ground beetle species is provided.

PMID- 22365950
TI  - Accumulation of pericardial fat correlates with left ventricular diastolic
      dysfunction in patients with normal ejection fraction.
AB  - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) plays an important role
      in heart failure with normal left ventricular ejection fraction (LVEF). Obesity
      is one of the major comorbid conditions of LVDD. Pericardial fat (PF) is an
      ectopic fat depot with possible paracrine or mechanical effects on the coronary
      circulation and myocardial function. METHODS: We measured PF volume on 64 slice
      computed tomography and analyzed echocardiographic parameters to confirm LVDD in
      229 consecutive patients suspected of coronary artery disease with LVEF of more
      than 50% and no symptomatic heart failure (59% men, 67+/-12 years). LVDD was
      defined as the ratio of transmitral Doppler early filling velocity to tissue
      Doppler early diastolic mitral annular velocity (E/e') >10. RESULTS: PF volume
      correlated significantly with E/e' (r=0.21, p<0.01), left ventricular mass index
      (r=0.23, p<0.001), and left atrial diameter (r=0.32, p<0.001). The mean PF volume
      was significantly greater in patients with LVDD (184+/-61cm(3), n=141) than in
      those without LVDD (154+/-58, n=88, p<0.001). Multivariate logistic regression
      analysis indicated that PF volume correlated significantly with the presence of
      LVDD (odds ratio: 2.00 per 100cm(3) increase in PF volume, p=0.02) independent of
      age, gender, abdominal obesity, hypertension, and diabetes. CONCLUSIONS: PF
      volumes are significantly associated with LVDD, independent of other factors such
      as hypertension or diabetes. PF may be implicated in the pathogenesis of LVDD in
      patients with normal LVEF.

PMID- 22365952
TI  - Aquaporin-4 mediates astrocyte response to beta-amyloid.
AB  - It has been demonstrated that the water channel protein aquaporin-4 (AQP4) plays
      an important role in astrocyte plasticity in response to a variety of injuries or
      stimuli. However, the potential role of AQP4 in astrocyte response to beta
      amyloid (Abeta) has not been studied. The purpose of this study was to
      investigate this issue. Compared to media control, the lower concentrations of
      Abeta(1-42) (0.1-1 MUM) increased AQP4 expression in cultured mouse cortical
      astrocytes, while the higher concentrations of Abeta(1-42) (10 MUM) decreased
      AQP4 expression. AQP4 gene knockout reduced Abeta(1-42)-induced astrocyte
      activation and apoptosis, which was associated with a reduction in the uptake of
      Abeta via decreased upregulation of low-density lipoprotein receptor related
      protein-1. Moreover, time-course and levels of Abeta(1-42)-induced mitogen
      activated protein kinase phosphorylation were altered in AQP4 null astrocytes
      compared with wild-type controls. Our data reveal a novel role of AQP4 in the
      uptake of Abeta by astrocytes, indicating that AQP4 is a molecular target for
      Alzheimer's disease.

PMID- 22365953
TI  - The impact of preprinted prescription forms on medication prescribing errors in
      an ophthalmology clinic in northeast Thailand: a non-randomised interventional
      study.
AB  - OBJECTIVES: To understand the incidence and types of medication prescribing
      errors in a low resource setting ophthalmology clinic and to determine the impact
      of a preprinted prescription based on the hospital formulary (FormularyScript) on
      medication prescribing errors. DESIGN: Non-randomised interventional study.
      SETTING: Ophthalmology clinic in a teaching hospital in northeast Thailand.
      PARTICIPANTS: 4349 handwritten prescriptions collected from October 2009 to
      December 2009, and 4146 FormularyScripts collected from February 2010 to May
      2010. PRIMARY AND SECONDARY OUTCOME MEASURES: All prescriptions from the
      handwritten and FormularyScript groups were analysed for medication error rates
      by types (legibility, ambiguous, incomplete, abbreviation and accuracy) and
      subtypes (drug name, strength, which eye, route and dispensed amount). RESULTS:
      Comparison of error rates in the two groups showed a 10-fold reduction in the
      overall error rate using FormularyScript (32.9%-3.5%, p<0.001). FormularyScripts
      were associated with statistically significant (p<0.001) decreases in the
      following error types: legibility (16.1%-0.1%), incomplete (16.1%-0.1%) and
      abbreviation (3.1%-0.3%). There was no statistically significant change in
      accuracy errors (0.8%-0.6%, p=0.21). Ambiguous errors increased with
      FormularyScripts (0.6%-2.5%, p<0.001), likely due to the introduction of new ways
      to make errors. Decreases were seen in all legibility, abbreviation and accuracy
      error subtypes, and four out of six incomplete error subtypes. There were
      statistically significant increases in both ambiguous error subtypes: which eye
      (0.3%-2.5%, p<0.001) and drug name (0.3%-0.6%, p=0.03). CONCLUSIONS: In our study
      population, outpatient medication prescribing errors were common and primarily
      due to legibility and incomplete error types. A preprinted prescription form has
      the potential to decrease medication prescribing errors related to legibility,
      incomplete prescribing information and use of unacceptable abbreviations without
      changing the overall rate of accuracy errors. However, new error types can occur.

PMID- 22365954
TI  - Pharmacokinetic and pharmacodynamic properties of SOL1: a novel dual inhibitor of
      neutral endopeptidase and endothelin converting enzyme.
AB  - AIMS: The pharmacological profile of the novel putative neutral endopeptidase
      (NEP) and endothelin converting enzyme (ECE) inhibitor SOL1 was examined. MAIN
      METHODS: The enzyme inhibitory profile of SOL1 was established in vitro. The
      pharmacokinetic and pharmacodynamic profile was determined in rodents in vivo.
      KEY FINDINGS: In vitro, at neutral pH, 10 MUM SOL1 inhibited NEP-1, NEP-2, and
      ECE-1 by 99%, 94% and 75%, respectively. The IC(50)s were 25, 25 and 3200 nmol/L,
      respectively. In anesthetized rats, SOL1 inhibited blood pressure (BP) responses
      to big-ET-1 and ET-1(1-31) with ED(50)s of 1.9 and 0.03 mg/kg, corresponding to
      plasma EC(50)s of 4.6 and 0.1 MUmol/L, respectively. Pharmacokinetics of SOL1
      were examined after single injections in mice and rats. In these species, the
      estimated clearance of SOL1 varied between 5 and 9 ml/kg.min and T(1/2) between
      20 and 60 min. Steady state kinetics of SOL1 were examined after continuous s.c.
      infusions of SOL1 for 3 weeks at 50mg/kg.day in DOCA-salt hypertensive rats. This
      treatment lowered BP by 22 mmHg. Steady state concentrations of SOL1 in plasma
      were 3.9 MUmol/L. In heart, lung, and kidney the concentrations of SOL1 were 0.4,
      1.8, and 20.5 MUmol/kg, respectively. About 63% of the daily dose was retrieved
      unaltered in the urine. SIGNIFICANCE: These data indicate that SOL1 is primarily
      a NEP inhibitor in vitro as well as in vivo. Given the preferential renal
      accumulation and renal clearance of SOL1 additional ECE-1 inhibition in the
      kidney may have contributed to its chronic BP lowering effects in the DOCA-salt
      hypertensive rat model.

PMID- 22365955
TI  - Comparison of endothelin receptors in normal versus cirrhotic human liver and in
      the liver from endothelial cell-specific ETB knockout mice.
AB  - AIMS: Endothelin (ET) antagonists show promise in animal models of cirrhosis and
      portal hypertension. The aim was to pharmacologically characterise the expression
      of endothelin receptors in human liver, hepatic artery and portal vein. MAIN
      METHODS: Immunofluorescence staining, receptor autoradiography and competition
      binding assays were used to localise and quantify ET receptors on hepatic
      parenchyma, hepatic artery and portal vein in human cirrhotic or normal liver.
      Additional experiments were performed to determine the affinity and selectivity
      of ET antagonists for liver ET endothelin receptors. An endothelial cell ET(B)
      knockout murine model was used to examine the function of sinusoid endothelial
      ET(B) receptors. KEY FINDINGS: ET(B) receptors predominated in normal human liver
      and displayed the highest ratio (ET(B):ET(A) 63:47) compared with other
      peripheral tissues. In two patients examined, liver ET(B) expression was up
      regulated in cirrhosis (ET(B):ET(A) 83:17). Both sub-types localised to the media
      of normal portal vein but ET(B) receptors were downregulated fivefold in the
      media of cirrhotic portal vein. Sinusoid diameter was fourfold smaller in
      endothelial cell ET(B) knockout mice. The liver morphology of ET(B) knockout mice
      was markedly different to normal murine liver, with loss of the wide spread
      sinusoidal pattern. In the knockout mice, sinusoids were reduced in both number
      and absolute diameter, while large intrahepatic veins were congested with red
      blood cells. SIGNIFICANCE: These data support a role for the ET system in
      cirrhosis of the liver and suggest that endothelial ET(B) blockade may cause
      sinusoidal constriction which may contribute to hepatotoxicity associated with
      some endothelin antagonists.

PMID- 22365956
TI  - Involvement of the endothelin and nitric oxide systems in the pathogenesis of
      renal ischemic damage in an experimental diabetic model.
AB  - AIMS: Ischemic acute kidney injury (iAKI) in experimental diabetes mellitus (DM)
      is associated with a rapid kidney dysfunction more than in non-diabetic rats. We
      hypothesize that this vulnerability is due to excessive endothelin-1 (ET-1)
      expression along with dysregulation of nitric oxide synthase (NOS) isoforms. The
      aim of the present study was to assess the impact of ischemia on renal function
      in diabetic rats as compared with non-diabetic rats, and to investigate the
      involvement of ET-1 and NO systems in the susceptibility of diabetic kidney to
      ischemic damage. MAIN METHODS: DM was induced by Streptozotocin. iAKI was induced
      by clamping of left renal artery for 30 min. Right intact kidney served as
      control. 48 h following ischemia, clearance protocols were applied to assess
      glomerular filtration rate (GFR), urinary flow (V) and sodium excretion (U(Na)V)
      in both kidneys. The renal effects of ABT-627, ET(A) antagonist; A192621.1, ET(B)
      antagonist; L-NAME, NOS non-selective inhibitor; 1400 W, inducible NOS (iNOS)
      inhibitor; and NPLA, neuronal NOS (nNOS) inhibitor, were assessed following
      ischemic renal injury in diabetic rats. KEY FINDINGS: Induction of iAKI in
      diabetic and non-diabetic rats caused significant reductions in GFR, V, and
      U(Na)V, which were greater in diabetic than non-diabetic rats. While, treatment
      with ABT-627 decreased V and U(Na)V, and increased GFR, A192621.1 decreased all
      these parameters. L-NAME, 1400 W, and NPLA improved GFR in the ischemic diabetic
      kidney. SIGNIFICANCE: Excessive vasoconstrictive effects of ET-1 via ET(A) and
      upregulation of iNOS, are partly responsible for the impaired recovery of renal
      function following ischemia in diabetic rats.

PMID- 22365957
TI  - Implications of maternal nutrient restriction in transgenerational programming of
      hypertension and endothelial dysfunction across F1-F3 offspring.
AB  - AIMS: An extensive variety of prenatal insults are associated with an increased
      incidence of metabolic and cardiovascular disorders in adult life. We previously
      demonstrated that maternal global nutrient restriction during pregnancy leads to
      increased blood pressure and endothelial dysfunction in the adult offspring. This
      study aimed to assess whether prenatal exposure to nutritional insult has
      transgenerational effects in F2 and F3 offspring. MAIN METHODS: For this, female
      Wistar rats were randomly divided into two groups on day 1 of pregnancy: a
      control group fed standard chow ad libitum and a restricted group fed 50% of the
      ad libitum intake throughout gestation. At delivery, all animals were fed a
      standard laboratory chow diet. At 11 weeks of age, one female and one male from
      each restricted litter were randomly selected and mated with rats from another
      restricted litters in order to generate the F2 offspring. The same procedure
      produced F3 generation. Similarly, the rats in the control group were bred for
      each generation. KEY FINDINGS: Our findings show that the deleterious effects of
      maternal nutrient restriction to which the F0 mothers were exposed may not be
      limited to the male first generation. In fact, we found that elevated blood
      pressure, an impaired vasodilatory response to acetylcholine and alterations in
      NO production were all transferred to the subsequent males from F2 and F3
      generations. SIGNIFICANCE: Our data show that global nutrient restriction during
      pregnancy results in a specific phenotype that can be passed transgenerationally
      to a second and third generation.

PMID- 22365960
TI  - Effects of different physical training protocols on ventricular oxidative stress
      parameters in infarction-induced rats.
AB  - AIM: Physical exercise is important in the prevention and treatment of
      cardiovascular diseases. Nevertheless, controversy remains around type and
      intensity of effort required for significant biochemical protective changes. This
      study investigates two exercise protocols on ventricular oxidative parameters in
      rats post-infarction. MAIN METHODS: Thirty-six 2-month-old male Wistar rats were
      divided in two groups (n=18): Sham and acute myocardial infarction (AMI)
      conducted by blocking the coronary artery. Thirty days after AMI, animals were
      divided in 6 subgroups (n=6): sham, sham+continuous training (60 min),
      sham+interval training, AMI, AMI+continuous training, and AMI+interval training.
      Training was conducted in water (30-32 degrees C) 5 times a week for 6 weeks.
      Animals were sacrificed 48 h after the last exercise routine. Left ventricles
      were used for oxidative stress analyses (antioxidant enzyme activity and level,
      oxidative damage) and HIF1alpha and cit c oxidase expression. KEY FINDINGS: After
      AMI, both exercise models decreased superoxide levels significantly. Training
      routines did not alter SOD expression and activity, though CAT expression
      increased with continuous training and GPX level diminished in both training
      groups, which coincided with the increase in GPX activity. Lipid damage decreased
      only in the continuous training group, while protein damage decreased only in the
      interval training group. Cytochrome C increased in both groups, while HIF-1 alpha
      dropped significantly after both exercise protocols. SIGNIFICANCE: Significant
      improvement occurred in myocardium redox status in rats challenged with AMI after
      different training routines. However, continuous training seems to be more
      efficient in improving the parameters analyzed.

PMID- 22365958
TI  - The effect of endothelin receptor A antagonism on basilar artery endothelium
      dependent relaxation after ischemic stroke.
AB  - AIMS: Endothelin (ET) receptor A antagonism decreases neuronal damage in
      experimental models of stroke. Since large arteries like basilar artery
      contribute significantly to total cerebrovascular resistance and are major
      determinants of microvascular pressure, dysregulation of basilar artery function
      may worsen stroke injury. ET-1 is involved in the regulation of basilar
      constriction. However, whether stroke influences vasoreactivity of basilar artery
      and to what extent ET-1 contributes to basilar vascular dysfunction after stroke
      remained unknown. The goal of this study was to test the hypothesis that ET-1
      impairs basilar artery vasorelaxation after ischemia/reperfusion (I/R) injury via
      activation of ET(A) receptor. MAIN METHODS: Male Wistar rats were subjected to 3h
      middle cerebral artery occlusion (MCAO) and 21 h reperfusion. One group received
      ET(A) receptor antagonist atrasentan (5 mg/kg, i.p.) at reperfusion. At 24h,
      basilar arteries were isolated from control non-stroked, stroked and
      stroked+atrasentan-treated animals for vascular reactivity measurements using
      pressurized arteriograph. KEY FINDINGS: Acetylcholine (Ach)-induced maximum
      relaxation (R(max)) was decreased in stroked animals as compared to non-stroked
      group and ET(A) antagonism partially restored it. There was also a trend for
      decreased EC(50) value for the antagonist treatment group indicating improved Ach
      sensitivity. SIGNIFICANCE: These findings suggest that I/R not only affects
      vessels distal to the occlusion but also impairs relaxation of proximal large
      vessels. ET-1-mediated basilar artery dysfunction may contribute to neurovascular
      damage after stroke and early restoration of vascular function by ET receptor
      antagonism after I/R injury may offer a therapeutic strategy.

PMID- 22365959
TI  - Defining the genetic architecture of human developmental language impairment.
AB  - Language is a uniquely human trait, which poses limitations on animal models for
      discovering biological substrates and pathways. Despite this challenge, rapidly
      developing biotechnology in the field of genomics has made human genetics studies
      a viable alternative route for defining the molecular neuroscience of human
      language. This is accomplished by studying families that transmit both normal and
      disordered language across generations. The language disorder reviewed here is
      specific language impairment (SLI), a developmental deficiency in language
      acquisition despite adequate opportunity, normal intelligence, and without any
      apparent neurological etiology. Here, we describe disease gene discovery
      paradigms as applied to SLI families and review the progress this field has made.
      After review the evidence that genetic factors influence SLI, we discuss methods
      and findings from scans of the human chromosomes, including the main replicated
      regions on chromosomes 13, 16 and 19 and two identified genes, ATP2C2 and CMIP
      that appear to account for the language variation on chromosome 16. Additional
      work has been done on candidate genes, i.e., genes chosen a priori and not
      through a genome scanning studies, including several studies of CNTNAP2 and some
      recent work implicating BDNF as a gene x gene interaction partner of genetic
      variation on chromosome 13 that influences language. These recent developments
      may allow for better use of post-mortem human brain samples functional studies
      and animal models for circumscribed language subcomponents. In the future, the
      identification of genetic variation associated with language phenotypes will
      provide the molecular pathways to understanding human language.

PMID- 22365961
TI  - Neonatal repetitive maternal separation causes long-lasting alterations in
      various neurotrophic factor expression in the cerebral cortex of rats.
AB  - AIMS: This study was carried out to examine the effects of early postnatal
      maternal separation stress on the development of the cerebral cortex with respect
      to time-dependent fluctuations of neurotrophic factor ligand and receptor
      expression. MAIN METHODS: Wistar rats were separated from their mothers for 3h
      per day during postnatal days (PND) 10 to 15. The cerebral cortex was analyzed by
      real-time RT-PCR for the evaluation of the expression of mRNA for brain-derived
      neurotrophic factor (BDNF), TrkB, insulin-like growth factor-1 (IGF-1), and type
      1 IGF receptor (IGF-1R) on PND16, 20, 30, and 60. KEY FINDINGS: The expression of
      these neurotrophic factor ligands and receptors in the cerebral cortex was
      enhanced on PND16 and PND20, and then it returned to baseline levels on PND30. By
      PND60, however, the expression levels were attenuated. SIGNIFICANCE: The
      important implication of this study is the persistent abnormal fluctuation of
      neurotrophic factor expression for a prolonged period, triggered even after the
      brain growth spurt. Given that neurotrophic factors play important roles in brain
      development, it can be speculated that the altered expression of these factors
      induced by maternal separation may interrupt normal brain development and
      ultimately lead to functional disruption. However, the possibility of such
      changes leading to various functional disruptions and the underlying mechanisms
      involved require further study.

PMID- 22365962
TI  - Identification of ITGB4BP as a new interaction protein of P311.
AB  - AIMS: P311 is an 8 kDa protein that has been shown to be of importance in the
      process of myofibroblast transformation, glioblastoma invasion and nerve
      regeneration. However, the interaction protein of P311 has yet to be found. The
      purpose of this study was to find the interactive protein of P311. MAIN METHODS:
      The yeast two-hybrid system was used for screening the potential interaction
      proteins of P311. Joint expression of the potential interactive protein and P311
      was immunohistochemically stained. The interaction between P311 and the selected
      protein was further confirmed by fluorescence resonance energy transfer (FRET) in
      pulmonary adenocarcinoma tissue sections, and by coimmunoprecipitation in HEK293.
      KEY FINDINGS: Integrin beta4 binding protein (ITGB4BP) was confirmed as the
      interaction protein of P311. Co-expression and interaction of ITGB4BP and P311
      were demonstrated in pulmonary adenocarcinoma by both immunohistochemistry and
      FRET. Moreover the interaction between P311 and ITGB4BP was demonstrated by
      coimmunoprecipitation in HEK293. SIGNIFICANCE: The interactions between P311 and
      ITGB4BP may be very important in the process of tumor cell differentiation and
      metastasis. ITGB4BP may provide a potential new target for the therapy of tumors.

PMID- 22365963
TI  - Alteration in lymphocyte population and humoral immune response in type 2
      diabetic Goto-Kakizaki rats.
AB  - AIMS: Proinflammatory cytokine production by a skewed T cell compartment has been
      shown to be elevated in patients with type 2 diabetes (T2D). However, it is
      unknown whether humoral immune response controlled by lymphocytes is altered in
      T2D. MAIN METHODS: Lymphocyte populations and immunoglobulin production were
      investigated in Goto-Kakizaki (G-K) rat, which is a genetic experimental model
      for T2D, and Wistar rat as a control. Each lymphocyte population was analyzed
      using flow cytometry. Immunoglobulin in plasma was measured before and after
      immunization with ovalbumin. The immunoglobulin subclasses and ovalbumin-specific
      immunoglobulins were measured by enzyme-immunoassay. Effects of improvement in
      hyperglycemia of G-K rats by chronic diet restriction on lymphocyte populations
      were also investigated. KEY FINDINGS: T/B lymphocyte ratios in blood and spleen
      from the G-K rats were significantly higher than those from the Wistar rats. The
      difference in the T/B cell ratio in blood of the G-K and Wistar rats was not
      affected by the diet restriction and the immunization. The ability of
      immunoglobulin production in G-K rats was comparable to that in Wistar rats,
      while the levels of natural IgM and ovalbumin-specific IgG2a were higher in
      plasma from the G-K rats than in plasma from the Wistar rats. SIGNIFICANCE: Since
      helper T cell type 2 (Th2) is known to regulate the class switch to IgG2a in
      rats, the results of this study suggest that G-K rats are characterized as
      immunologically Th2 dominant, resulting in increases in natural IgM and T/B cell
      ratio.

PMID- 22365964
TI  - ET-1 from endothelial cells is required for complete angiotensin II-induced
      cardiac fibrosis and hypertrophy.
AB  - AIMS: Hypertensive patients develop cardiac hypertrophy and fibrosis with
      increased stiffness, contractile deficit and altered perfusion. Angiotensin II
      (AngII) is an important factor in the promotion of this pathology. The effects of
      AngII are partly mediated by endothelin-1 (ET-1) and transforming growth factor
      beta. The exact feature of these pathways and the intercellular communications
      involved remain unclear. In this study, we explored the role of endothelial cell
      derived ET-1 in the development of AngII-induced cardiac fibrosis and
      hypertrophy. MAIN METHODS: We used mice with vascular endothelial cell specific
      ET-1 deficiency (VEETKO) and their wild type littermates (WT). Mice were infused
      for one week with AngII (3.2mg/kg/day, n=12) or vehicle (0.15 mol/L NaCl and 1
      mmol/L acetic acid, n=5), using subcutaneous mini-pumps. Hearts were stained with
      hematoxylin-eosin and masson's trichrome for histology. Cardiac gene expression
      and protein abundance were measured by Northern Blot, real time PCR and Western
      Blot. KEY FINDINGS: AngII-induced cardiac hypertrophy, interstitial and
      perivascular fibrosis were less pronounced in VEETKO mice compared to WT. Blood
      pressure increased similarly in both genotypes. Expression of connective tissue
      growth factor, tumor growth factor-beta, collagen I and III in response to AngII
      required endothelial ET-1. Endothelial ET-1 was also necessary to the elevation
      in protein kinase C delta abundance and ERK1/2 activation. AngII-induced
      elevation in PKCepsilon abundance was however ET-1 independent. SIGNIFICANCE:
      This study underscores the significance of ET-1 from the vasculature in the
      process of AngII-induced cardiac hypertrophy and fibrosis, independently from
      blood pressure. Endothelial ET-1 represents therefore a possible pharmacological
      target.

PMID- 22365965
TI  - Intracellular localization of nicotinic acetylcholine receptors in human cell
      lines.
AB  - AIMS: Previously we demonstrated that mouse liver mitochondria express functional
      alpha7 nicotinic acetylcholine receptors (nAChRs). The aim of this study was to
      investigate whether the nAChRs are found in mitochondria of non-neuronal human
      cell lines. MAIN METHODS: Three cell lines: U373 (astrocytes), U937 (monocytes)
      and Daudi (B lymphocytes) were examined by flow cytometry, Cell ELISA and
      fluorescent confocal microscopy using the antibodies against extracellular
      epitopes of alpha3, alpha4, alpha7, alpha9, beta2 and beta4 nAChR subunits. KEY
      FINDINGS: It is shown that the studied cells expressed different sets of nAChR
      subunits on the plasma membrane suggesting the presence of alpha7 nAChRs on all
      cells, of alpha3beta4 nAChRs on U373 cells and of alpha4beta2/alpha4beta4 nAChRs
      on U937 cells. In addition to nAChRs exposed on the surface, all cells contained
      a considerable intracellular pool of alpha3- and alpha7-containing nAChRs. The
      binding of alpha3-, alpha7- and beta4-specific antibodies partially overlapped
      with that of mitochondrial outer membrane translocase-specific antibody. Binding
      of alpha7-specific antibody also overlapped with that of MitoTracker Green, which
      binds to active mitochondria. SIGNIFICANCE: The data obtained suggest that a part
      of intracellular alpha3beta4 and alpha7 nAChRs in U373, U937 and Daudi cells is
      located on mitochondria. This finding complements our previous observation of
      alpha7 nAChRs in mouse liver mitochondria and reveals new intracellular targets
      for cholinergic regulation.

PMID- 22365966
TI  - Functional characterization of the p53 binding site in the human PYNOD promoter.
AB  - Many members of the NOD-like receptor (NLR) family play important roles in
      pathogen recognition and inflammation. However, human PYNOD, an NLR-like protein
      consisting of a pyrin domain and a nucleotidebinding and oligomerization domain
      (NOD), has been reported to inhibit inflammatory signals. Using bioinformatics,
      we found a completely preserved canonical p53 binding site in the PYNOD core
      promoter (-228 to -237 bp) both in humans and in chimpanzees. In this study, we
      investigated the characterization and biologic function of this binding site in
      vitro. The results show that either deletion of the p53 binding elements within
      the PYNOD promoter or treatment with p53 inhibitor (PFT-alpha) could
      significantly reduce PYNOD promoter activity and PYNOD expression as detected by
      the enhanced green fluorescent protein (EGFP) reporter system, reverse
      transcription-polymerase chain reaction, and Western blot respectively.
      Furthermore, the chromatin immunoprecipitation (ChIP) method confirmed that p53
      could bind to the PYNOD promoter. Our findings suggest that the p53 binding site
      plays a positive role in regulating PYNOD gene expression, which may maintain an
      efficient balance between defense and self-inflicted injury in respond to
      pathogen invasion.

PMID- 22365967
TI  - Tumor necrosis factor-alpha -308 G>A and interleukin-6 -174 G>C promoter
      polymorphisms and pemphigus.
AB  - The objective of this study was to analyze the possible involvement of the tumor
      necrosis factor (TNF)-alpha -308 G>A and interleukin-6 (IL-6) -174 G>C
      polymorphisms in the susceptibility and/or disease profile of pemphigus in
      Egyptian patients. Detection of TNF-alpha -308 G>A by amplification refractory
      mutation system and IL-6 -174 G>C by restriction fragment length polymorphism was
      performed for 70 patients and 203 controls. No significant differences were
      observed in the distribution of TNF-alpha -308 in pemphigus patients and
      controls. However, GA+AA genotypes were more frequent in pemphigus vulgaris (PV)
      patients only versus controls (p(c) = 0.046). The frequency of the C allele and
      CC/GC genotypes of IL-6 -174 was significantly higher in pemphigus patients and
      those with the 2 major clinical forms (PV and pemphigus foliaceus [PF]) compared
      with controls (p < 0.05). Comparison of the distribution of TNF-alpha -308 and IL
      6 -174 variants in relation to clinical type of pemphigus (PV versus PF),
      activity score, recurrence, and demographic data of patients revealed no
      significant associations. The IL-6 -174 CC genotype represents a marker of
      increased susceptibility to pemphigus in Egyptian patients and GG genotype can be
      considered a low-risk genotype; TNF-alpha -308 A-containing genotypes contribute
      to the susceptibility to PV only.

PMID- 22365968
TI  - Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa
      DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin.
AB  - High-frequency alleles and/or co-occurring human leukocyte antigen (HLA) alleles
      across loci appear to be more important than individual alleles, because they
      might be markers of disease risk that have clinical value as biomarkers for
      targeted screening or the development of new therapies. To better elucidate the
      major histocompatibility complex background and to facilitate the experimental
      use of cynomolgus macaques, Mafa-B, Mafa-DQB1, and Mafa-DRB alleles were
      characterized and their combinations were investigated from 30 macaques of
      Vietnamese origin by cloning and sequencing. A total of 48 Mafa-B, 22 Mafa-DQB1,
      and 42 Mafa-DRB alleles, were detected in this study, respectively. In addition,
      two Mafa-DQB1 and eight Mafa-DRB alleles represented novel sequences that had not
      been documented in earlier studies. Our results also showed that the macaque from
      Vietnam might be valuable because >30% of the test animals possessed Mafa
      DRB*w304 (30%) and -DQB1*0616 (30%). We report that the combination of major
      histocompatibility complex (MHC) class I and II alleles, including the
      combination of DRB3*0403-DRB*w304, DRB1*1013-DRB*w304, and Mafa-B*007:01:01
      DRB*w304, which was in 17%, 13%, and 13% of the animals, respectively.
      Interesting, more than two Mafa-DQB1 alleles detected in one animal in this study
      suggest that Mafa-DQB1, like Mafa-DRB, might be a duplication in the chromosome,
      which have ever been documented in cynomolgus monkeys but has not yet been
      observed in rhesus macaques or other primates. Our results for the high frequency
      of commonly co-occurring MHC alleles across loci in a cohort of the Vietnamese
      cynomolgus macaque emphasized the value of this species as a model for biomedical
      research.

PMID- 22365969
TI  - Determining the mechanism of membrane permeabilizing peptides: identification of
      potent, equilibrium pore-formers.
AB  - To enable selection and characterization of highly potent pore-forming peptides,
      we developed a set of novel assays to probe 1) the potency of peptide pores at
      very low peptide concentration; 2) the presence or absence of pores in membranes
      after equilibration; 3) the interbilayer exchangeability of pore-forming
      peptides; and 4) the degree to which pore-forming peptides disrupt the bilayer
      organization at equilibrium. Here, we use these assays to characterize, in
      parallel, six membrane-permeabilizing peptides belonging to multiple classes. We
      tested the antimicrobial peptides LL37 and dermaseptin S1, the well-known natural
      lytic peptides melittin and alamethicin, and the very potent lentivirus lytic
      peptides LLP1 and LLP2 from the cytoplasmic domain of HIV GP41. The assays
      verified that that the antimicrobial peptides are not potent pore formers, and
      form only transient permeabilization pathways in bilayers which are not
      detectable at equilibrium. The other peptides are far more potent and form pores
      that are still detectable in vesicles after many hours. Among the peptides
      studies, alamethicin is unique in that it is very potent, readily exchanges
      between vesicles, and disturbs the local bilayer structure even at very low
      concentration. The equally potent LLP peptides do not exchange readily and do not
      perturb the bilayer at equilibrium. Comparison of these classes of pore forming
      peptides in parallel using the set of assays we developed demonstrates our
      ability to detect differences in their mechanism of action. Importantly, these
      assays will be very useful in high-throughput screening where highly potent pore
      forming peptides can be selected based on their mechanism of action.

PMID- 22365970
TI  - Ceramide channels: influence of molecular structure on channel formation in
      membranes.
AB  - The sphingolipid, ceramide, self-assembles in the mitochondrial outer membrane
      (MOM), forming large channels capable of translocating proteins. These channels
      are believed to be involved in protein release from mitochondria, a key decision
      making step in cell death. Synthetic analogs of ceramide, bearing modifications
      in each of the major structural features of ceramide were used to probe the
      molecular basis for the stability of ceramide channels. Channel stability and
      mitochondrial permeabilization were disrupted by methylation of the C1-hydroxyl
      group whereas modifications of the C3 allylic hydroxyl group were well tolerated.
      A change in chirality at C2 that would influence the orientation of the C1
      hydroxyl group resulted in a strong reduction of channel-forming ability.
      Similarly, methylation of the amide nitrogen is also detrimental to channel
      formation. Many changes in the degree, location and nature of the unsaturation of
      ceramide had little effect on mitochondrial permeabilization. Competition
      experiments between ceramide and analogs resulted in synergy with structures
      compatible with the ceramide channel model and antagonism with incompatible
      structures. The results are consistent with ceramide channels being highly
      organized structures, stabilized by specific inter-molecular interactions,
      similar to the interactions responsible for protein folding.

PMID- 22365971
TI  - SITVITWEB--a publicly available international multimarker database for studying
      Mycobacterium tuberculosis genetic diversity and molecular epidemiology.
AB  - Among various genotyping methods to study Mycobacterium tuberculosis complex
      (MTC) genotypic polymorphism, spoligotyping and mycobacterial interspersed
      repetitive units-variable number of DNA tandem repeats (MIRU-VNTRs) have recently
      gained international approval as robust, fast, and reproducible typing methods
      generating data in a portable format. Spoligotyping constituted the backbone of a
      publicly available database SpolDB4 released in 2006; nonetheless this method
      possesses a low discriminatory power when used alone and should be ideally used
      in conjunction with a second typing method such as MIRU-VNTRs for high-resolution
      epidemiological studies. We hereby describe a publicly available international
      database named SITVITWEB which incorporates such multimarker data allowing to
      have a global vision of MTC genetic diversity worldwide based on 62,582 clinical
      isolates corresponding to 153 countries of patient origin (105 countries of
      isolation). We report a total of 7105 spoligotype patterns (corresponding to
      58,180 clinical isolates) - grouped into 2740 shared-types or spoligotype
      international types (SIT) containing 53,816 clinical isolates and 4364 orphan
      patterns. Interestingly, only 7% of the MTC isolates worldwide were orphans
      whereas more than half of SITed isolates (n=27,059) were restricted to only 24
      most prevalent SITs. The database also contains a total of 2379 MIRU patterns
      (from 8161 clinical isolates) from 87 countries of patient origin (35 countries
      of isolation); these were grouped in 847 shared-types or MIRU international types
      (MIT) containing 6626 isolates and 1533 orphan patterns. Lastly, data on 5-locus
      exact tandem repeats (ETRs) were available on 4626 isolates from 59 countries of
      patient origin (22 countries of isolation); a total of 458 different VNTR
      patterns were observed - split into 245 shared-types or VNTR International Types
      (VIT) containing 4413 isolates) and 213 orphan patterns. Datamining of SITVITWEB
      further allowed to update rules defining MTC genotypic lineages as well to have a
      new insight into MTC population structure and worldwide distribution at country,
      sub-regional and continental levels. At evolutionary level, the data compiled may
      be useful to distinguish the occasional convergent evolution of genotypes versus
      specific evolution of sublineages essentially influenced by adaptation to the
      host. This database is publicly available at: http://www.pasteur
      guadeloupe.fr:8081/SITVIT_ONLINE.

PMID- 22365972
TI  - Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent
      manner.
AB  - Hedgehog (Hh) signaling, via the key signal transducer Smoothened (SMO) and Gli
      transcription factors, is essential for embryonic development and carcinogenesis.
      While the biological relevance of hedgehog signaling to cancer is well
      established, very little is known about the molecular mechanisms by which
      signaling transduction of this pathway occurs. Rab23 was discovered as a negative
      regulator of the Hh pathway through a mouse genetic study. Here we report that
      Rab23 directly associates with Su(Fu) and inhibits Gli1 function in a Su(Fu)
      dependent manner. By confocal microscope and immunoprecipitation, we detected
      interaction between Rab23 and Su(Fu). Using Gli1-mediated reporter gene analysis,
      we found that Rab23 can suppress Gli1 transcriptional activity in wild type but
      not Su(Fu) null fibroblasts. Similarly, Rab23 expression reduced the nuclear
      localization of Gli1 in wild type but not Su(Fu) null fibroblast cells.
      Consistent with the GTPase motif in the protein, we showed that Rab23 has GTPase
      activity. The dominant negative form of Rab23 was unable to suppress Gli1
      mediated transcriptional activity. Taken together, these data provide evidence to
      support that Rab23 negatively regulates Gli1 activity in a Su(Fu)-dependent
      manner.

PMID- 22365973
TI  - Preservation of renal function in the modern staged repair of classic bladder
      exstrophy.
AB  - OBJECTIVE: To compare the estimated glomerular filtration rate (eGFR) in bladder
      exstrophy patients with published normative GFR estimates. PATIENTS AND METHODS:
      eGFR was calculated using the Schwartz formula at three timepoints, with mean
      eGFR at each timepoint compared to normative values. RESULTS: At primary closure
      (n = 53) the mean eGFR (ml/min/1.73 m(2)) in exstrophy patients was similar to
      norms at 0-7 days (exstrophy vs norm: 42.5 vs 40.6, p > 0.05) and after 2 years
      of age (108.8 vs 133, p > 0.05). However, the mean eGFR in exstrophy patients was
      significantly lower than norms between 8 days (44.8 vs 65.8, p < 0.0001) and 2
      years of life (68 vs 95.7, p = 0.01). At bladder neck reconstruction (n = 13) no
      statistically significant difference existed between the exstrophy and normative
      eGFR values (137.1 vs 133, p > 0.05). Similarly, among 27 patients with at least
      1 year follow-up after bladder neck reconstruction, the mean exstrophy eGFR was
      no worse or higher than normative values (2-12 years: 124.5 vs 133, p > 0.05;
      males >=13 years 175.6 vs 140, p = 0.04; females >=13 years 128.8 vs 126, p >
      0.05). CONCLUSION: The staged reconstruction of exstrophy does not appear to
      negatively impact renal function in most patients. As eGFR detects only
      significant changes, surgical reconstruction may still cause more subtle renal
      damage.

PMID- 22365974
TI  - MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel
      prognostic markers in Barrett's adenocarcinoma.
AB  - To characterize proteomic changes found in Barrett's adenocarcinoma and its
      premalignant stages, the proteomic profiles of histologically defined precursor
      and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary
      proteomic screening, a discovery cohort of 38 fresh frozen Barrett's
      adenocarcinoma patient tissue samples was used. The goal was to find proteins
      that might be used as markers for monitoring cancer development as well as for
      predicting regional lymph node metastasis and disease outcome. Using mass
      spectrometry for protein identification and validating the results by
      immunohistochemistry on an independent validation set, we could identify two of
      60 differentially expressed m/z species between Barrett's adenocarcinoma and the
      precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are
      differentially expressed in Barrett's adenocarcinoma cases with and without
      regional lymph node metastasis, one was identified as TAGLN2. In the validation
      set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a
      poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel
      independent prognostic factor in Barrett's adenocarcinoma. Our results underscore
      the high potential of MALDI imaging for revealing new biologically significant
      molecular details from cancer tissues which might have potential for clinical
      application. This article is part of a Special Issue entitled: Translational
      Proteomics.

PMID- 22365975
TI  - Human IgG Fc-glycosylation profiling reveals associations with age, sex, female
      sex hormones and thyroid cancer.
AB  - IgG functions rely on interactions of the Fc region with other proteins, which
      are optimized by tailoring of a conserved N-linked glycosylation at Asn-297. We
      conducted a study involving 735 control individuals and 138 thyroid cancer
      patients. Here we demonstrated that previously described age-related change in Fc
      glycosylation was further characterized by definite sex specificity. In females,
      the incidences of most of glycosylated forms began to pose characteristic changes
      at ages of puberty or menopause. In addition, glycan-glycan relationships existed
      extensively within Fc glycosylation, which were characterized to be altered upon
      different states of subjects, such as age, sex and thyroid cancer. In thyroid
      cancer patients, detailed comparison of glycosylation incidences with control
      individuals yielded insight into aberrant change in IgG(1) Fc-glycosylation. This
      aberrant pattern was also featured by remarkable specificities of both age and
      sex. The receiver operating characteristic curve analysis was used to determine
      diagnostic values of Fc glycosylation. Finally, clinical measurement of two major
      female sex hormones estradiol and progesterone was conducted to determine
      potential associations of hormones with IgG Fc glycosylation. This study provided
      an important view to the associations of IgG Fc N-linked glycosylation with age,
      sex, female sex hormones and thyroid cancer. This article is part of a Special
      Issue entitled: Proteomics: The clinical link.

PMID- 22365976
TI  - Differential modulations of striatal tyrosine hydroxylase and dopamine metabolism
      by cannabinoid agonists as evidence for functional selectivity in vivo.
AB  - It is generally assumed that cannabinoids induce transient modulations of
      dopamine transmission through indirect regulation of its release. However, we
      previously described a direct cannabinoid-mediated control of tyrosine
      hydroxylase (TH) expression, in vitro. We herein report on the influence of
      cannabinoid agonists on the expression of this key enzyme in catecholamine
      synthesis as well as on the modification of dopamine content in adult rats. As
      expected for cannabinoid agonists, the exposure to either Delta(9)-THC, HU 210 or
      CP 55,940 induced both catalepsy and hypolocomotion. Supporting a possible long
      lasting control on dopaminergic activity, we noticed a significant HU 210
      mediated increase in TH expression in the striatum that was concomitant with an
      increase in striatal dopamine content. Surprisingly, while a similar trend was
      reported with Delta(9)-THC, CP 55,940 completely failed to modulate TH expression
      or dopamine content. Nevertheless, the access of CP 55,940 to brain structures
      was validated by determinations of drug concentrations in the tissue and by ex
      vivo binding experiments. Furthermore, confirming the central activity of CP
      55,940, the analysis of dopamine metabolites revealed a reduction in striatal
      DOPAC concentrations. Consistent with the involvement of the CB(1) cannabinoid
      receptor in these different responses, both HU 210- and CP 55,940-mediated
      effects were prevented by SR 141716A. Therefore, the present data suggest that
      both HU 210 and CP 55,940 cause a delayed/persistent regulation of the dopamine
      neurotransmission system. Nevertheless, these commonly used cannabinoid agonists
      endowed with similar pharmacodynamic properties clearly triggered distinct
      biochemical responses highlighting the existence of functional selectivity in
      vivo.

PMID- 22365978
TI  - Metachronous manifestation of carcinoma ex pleomorphic adenoma in a buccal minor
      salivary gland and the contralateral parotid gland: a case report and review of
      the literature.

PMID- 22365977
TI  - Platelet-rich plasma promotes angiogenesis of prefabricated vascularized bone
      graft.
AB  - PURPOSE: The objective was to assess the impact of platelet-rich plasma (PRP) on
      angiogenesis and bone formation of tissue-engineered bone in the prefabricated
      stage. MATERIALS AND METHODS: Both thighs of New Zealand white rabbits were used
      as prefabricated vascularized bone grafts using a combination of bone mesenchymal
      stem cells and vascular bundles in a titanium cage filled with beta-tricalcium
      phosphate ceramic. PRP was applied in the test group, and the same procedure was
      performed in the control group without the application of PRP. After 4, 8, and 12
      weeks, delayed static bone scanning with technetium-99m methylene diphosphonate
      was performed before sacrifice, and the tissue-engineered bone samples were
      collected for immunohistochemical analysis using a monoclonal antibody against
      CD31 and histologic analysis. RESULTS: The results showed superior angiogenesis
      in the PRP group compared with the control group at each time point as determined
      by bone scintigraphy and immunohistochemical examinations. The results of
      histologic analysis also showed that there was more bone formation in the PRP
      group than in the control group at each time point. CONCLUSIONS: The application
      of autologous PRP was an effective strategy for increasing angiogenesis and bone
      formation in tissue-engineered bone and had potential significance for clinical
      applications.

PMID- 22365979
TI  - Nasal endoscopy-assisted reconstruction of orbital floor blowout fractures using
      temporal fascia grafting.
AB  - PURPOSE: To present the experience and outcomes of an endoscopy-assisted
      reconstruction of isolated orbital floor blowout fractures using temporalis
      fascia grafting. MATERIALS AND METHODS: A retrospective chart review of 32
      patients who underwent repair of orbital floor fractures using temporalis fascia
      grafting from January 1, 2004, through December 1, 2009, was conducted. All
      procedures were performed through an upper buccal sulcus incision and a
      transmaxillary endoscopic approach to the orbital floor. The area of displaced
      bone fragments was limited to 2 cm(2) in all patients in this study. The
      parameters evaluated before and after surgery included visual acuity, extraocular
      motility and diplopia, and exophthalmometry. All patients underwent computed
      tomography before and 6 months after surgery. RESULTS: None of the 32 patients
      had a postoperative clinical infection or obvious inflammation. Visual acuity was
      better than or equal to 20/100 in 43% of patients before surgery compared with
      76% of patients after surgery. All patients had diplopia before surgery; only 3
      had diplopia 6 months after surgery. Enophthalmos was observed in all patients
      before surgery, and 4 patients still displayed enophthalmos at 6 months after
      surgery. No sagging of the reconstructed orbital floor was found on computed
      tomograms 6 months after surgery. CONCLUSIONS: This retrospective study is the
      first to show that the temporalis fascia is a reliable implant for the repair of
      orbital floor defects smaller than or equal to 2 cm(2).

PMID- 22365980
TI  - Do histologic criteria predict biologic behavior of giant cell lesions?
AB  - PURPOSE: To determine whether the clinical behavior of giant cell lesions (GCLs)
      or their anatomic location can be differentiated by histologic criteria alone.
      MATERIALS AND METHODS: We performed a retrospective study of patients with GCLs
      treated at Massachusetts General Hospital between 1993 and 2008. Predictor
      variables were histologic parameters: number of giant cells (GCs) per high-power
      field, number of nuclei per GC, GC size, stromal cellularity, stromal type,
      presence of hemorrhage and reactive osteoid, and blinded pathologists' prediction
      of location and behavior. Outcome variables were clinical behavior (aggressive or
      nonaggressive) and GCL location, that is, maxillofacial (MF) or
      axial/appendicular (AA). Descriptive and bivariate statistics were computed with
      statistical significance set at P <= .05. RESULTS: The sample included 88
      subjects: 41 MF GCLs (35 aggressive) and 47 AA GCLs (28 aggressive). Aggressive
      AA lesions had more GCs per high-power field, larger mean GC size, and increased
      stromal cellularity, and they more frequently had a mononuclear stroma when
      compared with aggressive MF lesions (P < .05). There were no significant
      histologic differences between aggressive and nonaggressive MF lesions or between
      nonaggressive MF and nonaggressive AA lesions. Aggressive AA lesions had more
      nuclei/GC than nonaggressive AA lesions (P = .03). Using histologic criteria
      only, blinded pathologists predicted clinical behavior in only 45% of cases
      (kappa = 0.19, P = .09). They predicted a lesion's location in 82% of cases with
      fair agreement (kappa = 0.44, P < .01). CONCLUSIONS: Results of this study
      indicate that histologic differences between aggressive and nonaggressive GCLs
      are insufficient for pathologists to differentiate them consistently regardless
      of location.

PMID- 22365982
TI  - Interval between injury and lingual nerve repair as a prognostic factor for
      success using type I collagen conduit.
AB  - PURPOSE: The purpose of the present study was to investigate the role of a type I
      collagen nerve conduit in the repair of lingual nerve injuries compared with
      those lingual nerve repairs performed without a collagen membrane and to identify
      the prognostic factors for functional sensory recovery (FSR). MATERIALS AND
      METHODS: This was a retrospective cohort study evaluating a sample derived from
      the population of patients who had undergone lingual nerve microsurgery from
      March 17, 2000, to February 23, 2010 by the same surgeon (V.B.Z.) with complete
      records available, including follow-up assessments. The primary outcome variable
      was the interval to successful FSR according to the British Medical Research
      Council criteria for FSR. The predictor variables were categorized into
      demographic, surgical, and clinical sensory testing. Appropriate descriptive
      statistics and univariate and multivariate Cox proportional hazards survival
      statistics were computed in analyzing the patient age at lingual nerve injury
      repair (in years), gender, timing of surgical intervention, mechanism of injury,
      specific surgical procedures, and application of a type I collagen conduit.
      RESULTS: The study cohort included 41 patients with 42 lingual nerve injuries who
      underwent surgical repair. Their mean age was 28.3 +/- 8.3 years (range 13 to
      44), with 88% females (n = 32). In the multivariate model, the injury to surgery
      interval per 1-month increase (hazard ratio 1.23, 95% confidence interval 1.02 to
      1.48, P = .029) and injury to surgery interval of 9 months or longer (hazard
      ratio 4.67, 95% confidence interval 1.04 to 20.87, P = .04) remained
      significantly associated statistically with successful FSR. CONCLUSIONS: The
      results of the present study have demonstrated that the injury to surgery
      interval is the most significant prognostic factor in the repair of lingual nerve
      injuries. The use of the collagen membrane demonstrated a greater level of FSR
      compared with those treated without the use of the membrane. However, the results
      from the collagen conduit were not statistically significant.

PMID- 22365981
TI  - Inductive, scaffold-based, regenerative medicine approach to reconstruction of
      the temporomandibular joint disk.
AB  - PURPOSE: A device composed of extracellular matrix (ECM) was investigated as an
      inductive template in vivo for reconstruction of the temporomandibular joint
      (TMJ) disk after discectomy. MATERIALS AND METHODS: A scaffold material composed
      of porcine-derived ECM was configured to mimic the shape and size of the TMJ.
      This device was implanted in a canine model of bilateral TMJ discectomy. After
      discectomy, 1 side was repaired with an ECM scaffold material and the
      contralateral side was left empty as a control. At 6 months after implantation,
      the joint space was opened, the joints were evaluated for signs of gross
      pathologic degenerative changes, and newly formed tissue was excised for
      histologic, biochemical, and biomechanical analysis. RESULTS: The results showed
      that implantation of an initially acellular material supported the formation of
      site-appropriate, functional host tissue that resembled that of the native TMJ
      disk. Furthermore, this prevented gross degenerative changes in the temporal
      fossa and mandibular condyle. No tissue formation and mild to severe gross
      pathologic changes were observed in the contralateral controls. CONCLUSIONS:
      These results suggest that an ECM-based bioscaffold could represent an off-the
      shelf solution for TMJ disk replacement.

PMID- 22365983
TI  - Continuous de novo synthesis of neurosteroids is required for normal synaptic
      transmission and plasticity in the dentate gyrus of the rat hippocampus.
AB  - Both in vivo and in vitro studies have shown that neurosteroids promote learning
      and memory by modulating synaptic functions in the hippocampus. However, we do
      not know to what degree endogenously synthesized neurosteroids contribute to the
      hippocampal synaptic functions. Cytochrome P450scc is the enzyme that converts
      cholesterol to pregnenolone (PREG), which is required for the biosynthesis of all
      other neurosteroids. To investigate the physiological roles of endogenous
      neurosteroids in synaptic functions, we electrophysiologically examined the
      effects of aminoglutethimide (AG), a selective inhibitor of P450scc, on the
      synaptic transmission and plasticity in the dentate gyrus of rat hippocampal
      slices. The application of AG (100 MUM) decreased the slope of the field
      excitatory postsynaptic potentials (fEPSPs) in granule cells by 20-30% in 20 min
      through the modulation of postsynaptic AMPA receptors, while it did not affect
      the presynaptic properties, including the paired-pulse ratio and the probability
      of glutamate release from presynaptic terminals. The AG-induced depression was
      nearly completely rescued by exogenously applied 500 nM PREG or by 1 nM
      dehydroepiandrosterone sulfate (DHEAS), one of the neurosteroids synthesized from
      PREG, suggesting that the AG-induced depression was caused by the loss of DHEAS.
      AG also reduced NMDA receptor activity, and suppressed high-frequency stimulation
      (HFS)-induced long-term potentiation (LTP). These findings provide novel evidence
      that the endogenous neurosteroids locally synthesized in the brain are required
      to maintain the normal excitatory synaptic transmission and plasticity in the
      dentate gyrus of the rat hippocampus.

PMID- 22365984
TI  - In vitro upregulation of erythrocytes glucose uptake by Rhaphnus sativa extract
      in diabetic patients.
AB  - In diabetes, both the increase in the oxidative stress and the decrease in the
      antioxidant defense may elevate the susceptibility of diabetic patients to many
      pathological complications. So, the aim of the present study was to investigate
      the effect of superoxide dismutase (SOD) like activity protein, partially
      purified from radish (Rhaphnus sativa) on uptake of glucose in vitro by
      erythrocytes of diabetic patients. In hyperglycemic patients, erythrocytes
      malondialdehyde level was highly significantly increased (P < 0.0001) than that
      of the control. However, the erythrocytes glutathione content and glutathione
      reductase activity, were both highly significantly decreased (P < 0.0001)
      compared to that corresponding control values. The glucose uptake by erythrocytes
      of diabetic patients was highly significantly decreased (P < 0.0001) with
      increasing hyperglycemia, while it was highly significantly elevated (p < 0.0001)
      after addition of the partially purified SOD like activity protein. On the other
      hand, the malondialdehyde concentration was highly significantly reduced (p <
      0.001) on adding the partially purified protein. It thus can be concluded that,
      an appropriate support for enhancing antioxidant supply, such as SOD like
      activity protein from natural sources, may help control blood glucose level and
      may prevent clinical complications of diabetes.

PMID- 22365985
TI  - Overexpression of Ipe protein from the coliphage mEp021 induces pleiotropic
      effects involving haemolysis by HlyE-containing vesicles and cell death.
AB  - Lysogenic Escherichia coli K-12 harbouring the prophage mEp021 displays
      haemolytic activity. From a genomic library of mEp021, we identified an open
      reading frame (ORF 4) that was responsible for the haemolytic activity. However,
      the ORF 4 sequence contains four initiation codons in the same frame: ORF 4.1-ORF
      4.4, coding for 83-a.a., 82-a.a., 77-a.a. and 72-a.a. products, respectively. The
      expression of the cloned ORF 4.3, or inducer of pleiotropic effects (ipe),
      reproduced the haemolytic phenotype in a native strain carrying the gene hlyE(+),
      but not in the mutant hlyE(-) strain. The overexpression of Ipe induced several
      pleiotropic effects, such as the inhibition of cell growth and the deregulation
      of cell division, which resulted in a mixture of normal and desiccated-like
      cells: normal-filamentous, desiccated-like-filamentous bacilli, minicells etc.
      Other effects included abnormalities of the cell membrane, the production of
      vesicles containing HlyE, and finally, cell death. These events were analysed at
      the molecular level by microarray assays. The global transcription profile of E.
      coli K-12 strain MC4100, which expressed Ipe after 4 h, revealed differential
      expression of various genes, most of which were related either to cell membrane
      and murein biosynthesis or to cell division. The up-regulation of some of these
      transcripts was confirmed by qRT-PCR. Additional research is needed to determine
      whether these effects are directly related to Ipe activity or are consequences of
      the cellular responses to putative structural damage induced by Ipe.

PMID- 22365986
TI  - Structural investigation of HIV-1 genomic RNA dimerization process reveals a role
      for the Major Splice-site Donor stem loop.
AB  - The 5'UnTranslated Region (5'UTR) of HIV-1 genomic RNA, which precedes the Gag
      coding sequence, fulfills several roles during the lentivirus life cycle. This
      335 nucleotides leader contains many stable structures that are crucial for the
      regulation of genetic expression at the level of transcription, splicing, and
      translation. In the late steps of the virus cycle, i.e. virions formation, the
      genomic RNA serves as propagated genome and its encapsidation in new particles
      relies on its ability to form non-covalent dimers. Dimerization is proposed to be
      initiated by the intermolecular pairing of a self-complementary sequence located
      in the apical loop of the DIS hairpin (Dimer Initiation Sequence). The regulation
      of this phenomenon and the extraordinary stability of the dimers imply that
      structural elements other than this kissing complex remain to be identified.
      Here, we show that swapping the Gag open reading frame (ORF) by reporter genes
      interferes with dimers formation efficiency. Importantly, the nature of the ORF
      alters specific structures of the 5'UTR. By using a systematic "SHAPE" approach,
      we pointed out that sequences within the Major Splice Site are involved in the
      dimerization process. Furthermore, by the use of an antisense oligonucleotide
      specific for the MSD associated to a SHAPE analysis of the 5'UTR structure, we
      demonstrated that interfering with the MSD results both in an impaired
      dimerization and in modifications of the 5'UTR structure. All together these data
      support a recently proposed model in which intramolecular base pairings are
      important determinants for the dimerization process. We further conclude that
      much care should be taken when comparing translation activity of reporter
      constructs with the viral situation.

PMID- 22365987
TI  - Danon disease: a focus on processing of the novel LAMP2 mutation and comments on
      the beneficial use of peripheral white blood cells in the diagnosis of LAMP2
      deficiency.
AB  - Danon disease (DD) is a monogenic X-linked disorder characterized by
      cardiomyopathy, skeletal myopathy and variable degrees of intellectual
      disability. DD develops due to mutations in the gene encoding lysosomal
      associated membrane protein 2 (LAMP2). We report on a family exhibiting the
      clinical phenotype comprising of hypertrophic cardiomyopathy and ventricular pre
      excitation, myopia and mild myopathy in two male patients and cardiomyopathy and
      myopia in a female patient. The diagnosis of DD in this family was based on the
      assessment of the clinical phenotypes and the absence of LAMP2 in skeletal and/or
      cardiac muscle biopsy specimens. Sequence analysis of the LAMP2 gene and its mRNA
      revealed a novel LAMP2 mutation (c.940delG) in all three patients. Approximately
      25% of the female patient's cardiomyocytes were LAMP2 positive apparently due to
      the unfavorable skewing of X chromosome inactivation. We further performed
      qualitative LAMP2 immunohistochemistry on peripheral white blood cells using the
      smear technique and revealed the absence of LAMP2 in the male patients. LAMP2
      expression was further assessed in granulocytes, CD4+ and CD8+ T lymphocytes,
      CD20+ B lymphocytes, CD14+ monocytes and CD56+ natural killer cells by
      quantitative polychromatic flow cytometry. Whereas the male DD patients lacked
      LAMP2 in all WBC populations, the female patient expressed LAMP2 in 15.1% and
      12.8% of monocytes and granulocytes, respectively. LAMP2 expression ratiometrics
      of highly vs. weakly expressing WBC populations discriminated the DD patients
      from the healthy controls. WBCs are thus suitable for initial LAMP2 expression
      testing when DD is a differential diagnostic option. Moreover, flow cytometry
      represents a quantitative method to assess the skewing of LAMP2 expression in
      female heterozygotes. Because LAMP2 is a major protein constituent of the
      membranes of a number of lysosome-related organelles, we also tested the exocytic
      capacity of the lytic granules from CD8+ T lymphocytes in the patient samples.
      The degranulation triggered by a specific stimulus (anti-CD3 antibody) was
      normal. Therefore, this process can be considered LAMP2 independent in human T
      cells. The c.940delG mutation results in a putatively truncated protein
      (p.A314QfsX32), which lacks the transmembrane domain and the cytosolic tail of
      the wild-type LAMP2. We tested whether this variant becomes exocytosed because of
      a failure in targeting to late endosomes/lysosomes. Western blotting of cardiac
      muscle, WBCs and cultured skin fibroblasts (and their culture media) showed no
      intra- or extracellular truncated LAMP2. By comparing the expression pattern and
      intracellular targeting in cultured skin fibroblasts of normal LAMP2 isoforms (A,
      B and C) tagged with green fluorescent protein (GFP) and the A314Qfs32-GFP
      fusion, we found that the A314Qfs32-GFP protein is not even expressed. These
      observations suggest that the truncated protein is unstable and is co
      translationally or early post-translationally degraded.

PMID- 22365988
TI  - Purification and biochemical characterization of a novel protein-tongue cancer
      chemotherapy resistance-associated protein1 (TCRP1).
AB  - Multidrug resistance is a major obstacle to successful treatment of oral squamous
      cell carcinoma (OSCC). Lately, we found a novel human gene named tongue cancer
      chemotherapy resistance-associated protein1 (TCRP1) in the tongue cancer multi
      drug resistance cell line (Tca8113/PYM) established by us. In this study, we
      focus on recombinant expression, purification, and biochemical characterization
      of TCRP1. After molecular cloning and purification of the gene encoding the 24
      kDa protein, a mouse polyclonal antibody against TCRP1 was prepared, and the
      specialty of the antibody was confirmed by Western blot. The cell proliferation
      was evaluated by MTS assay and DNA damage was determined by comet assay, the
      results indicated that this protein especially mediated the cell's resistance to
      cisplatin; it was associated with its role of providing protection against DNA
      damage. We also found that TCRP1 expression was increased in cisplatin-resistant
      carcinoma cell lines (Tca/PYM and A549/DDP), but not in cisplatin-sensitive MDR
      cell lines (MCF-7/5-Fu), compared with their parental counterparts by Western
      blot analysis. Immunofluorescence and immunohistochemical analysis showed TCRP1
      is mainly expression in cytoplasmic, the Mann-Whitney U test exhibited that TCRP1
      positive patients predicted the worst sensitive with cisplatin of OSCC patients.
      All these findings suggest that TCRP1 is a novel cisplatin-resistant protein
      which is mainly localized in the cytoplasm and can mediate cisplatin resistance
      against DNA damage; the expression level of TCRP1 in patients with OSCC may be
      useful as an indicator of therapeutic efficacy of the sensitivity to cisplatin.

PMID- 22365989
TI  - Molecular cloning, characterization and expression of the complement component
      Bf/C2 gene in grass carp.
AB  - The complement system is an integral part of the host immune system and plays an
      immunoregulatory role at the interface between the innate and acquired immune
      responses. Factor B (Bf) serves as the catalytic subunit of complement C3
      convertase in the alternative pathway (AP), while in the classical pathway (CP),
      this function is subjected to C2. In this study, we cloned and characterized the
      two Bf/C2 genes of grass carp, gcBf/C2A and gcBf/C2B. The gcBf/C2A and gcBf/C2B
      cDNA sequences are 2259 and 3004 bp in length, and the open reading frames (ORFs)
      of gcBf/C2A and gcBf/C2B were found to encode peptides of 752 and 837 amino
      acids, respectively. The genes share 30.7% amino acid identity with each other
      and 32.4-38.3% and 31.4-33% with the Bf and C2 genes in humans and mice. GcBf/C2A
      and gcBf/C2B were expressed in a wide range of grass carp tissues, with the
      highest level of expression of both genes detected in the liver. After a
      challenge with Aeromonas hydrophila, gcBf/C2A was significantly upregulated,
      especially at 4 h after infection, and the significantly higher expression of
      gcBf/C2B (27.3-fold) was found in the head kidney at 24 h post-challenge. The
      expression of gcBf/C2A was quickly upregulated at 1 day post-hatching and peaked
      at 5 days post-hatching. The maximum expression of gcBf/C2B was found at 1 day
      post-hatching. In conclusion, our data enables a better understanding of the
      physiological function of the Bf/C2 complement genes in vertebrates.

PMID- 22365990
TI  - Stimulatory effects of chitinase on growth and immune defense of orange-spotted
      grouper (Epinephelus coioides).
AB  - Chitinase, belonging to either family 18 or family 19 of the glycosylhydrolases,
      hydrolyze chitin into oligosaccharides. In the present study, the cDNA fragment
      encoding orange-spotted grouper (Epinephelus coioides) chitinase1 was subcloned
      into pPIC3.5K vector and expressed in Pichia pastoris GS115. The results showed
      that a band with the size of about 53 kDa could be detected by SDS-PAGE and
      Western blot. The recombinant protein of grouper chitinase1 (rgChi1) was added
      into the fish diet containing shrimp shell chitin for feeding experiment lasting
      8 weeks. The weight of orange-spotted grouper, fed with diets containing rgChi1
      at 0, 5, 10 and 20 MUg/g was calculated on the 2nd, 4th, 6th and 8th weeks, and
      difference in growth rates was first observed in the 6th week of the feeding
      period and it kept until the end of the feeding experiment. At the end of 8 weeks
      feeding trial, the percent weight gain (PWG), growth rate (GR) and specific
      growth rate (SGR) of fish fed with 10 and 20 MUg rgChi1/g feed were significantly
      higher compared to the control group. The neuropeptide Y (NPY), growth-hormone
      releasing hormone (GHRH), growth-hormone (GH), interleukin-1beta (IL-1beta),
      cyclooxygenase-2 (COX-2), superoxide dismutase (SOD) (Cu/Zn) and SOD (Mn) mRNA
      expression of fish fed with diet containing 10 MUg/g or/and 20 MUg/g rgChi1 were
      obviously higher than the control group. The lysozyme (LZM) and total SOD
      activity of fish fed with diet containing rgChi1 at 10 and 20 MUg/g were
      significantly higher than that of the control. The aspartate aminotransferase
      (AST)/glutamic oxalacetic transaminases (GOT) activity in 20 MUg/g group
      decreased compared to the control group. These results indicated that the grouper
      chitinase1 was successfully produced using the P. pastoris expression system and
      the recombinant protein had obvious effects on growth and immune defense. The
      mRNA expression and protein secretion of grouper chitinase1 and chitinase2 were
      significantly stimulated in spleen in response to bacterial lipopolysaccharide
      (LPS) challenge, strongly suggesting the existence of an innate pathway for local
      defense against chitin-containing organisms. Moreover, the pathogen such as
      Escherichia coli and Staphylococcus aureus could be inhibited by the recombinant
      protein of grouper chitinase1 to a certain extent.

PMID- 22365991
TI  - First report of two thioredoxin homologues in crustaceans: molecular
      characterization, genomic organization and expression pattern in swimming crab
      Portunus trituberculatus.
AB  - Previously, we had reported two homologues of the thioredoxin (Trx) super-family
      (PtTrx1 and PtTrx2) identified from eyestalk and haemocytes cDNA library of
      swimming crab Portunus trituberculatus, respectively. It was the first report of
      two thioredoxin homologues from the same crustacean species. Here, we focused on
      the molecular characterization, genomic organization and expression pattern of
      PtTrx1 and PtTrx2. The full-length cDNA sequences of PtTrx1 and PtTrx2 were 739
      and 1300 bp, encoding 105 and 133 amino acids, respectively. They both had a
      conserved CGPC active site and highly similar tertiary structures, which
      containing four beta-sheets and four alpha-helixes. Specifically, PtTrx2 was
      encoded by a nuclear gene and its cellular localization was targeted to
      mitochondria by an N-terminal mitochondrial pre-sequence. Sequence analysis
      revealed PtTrx1 and PtTrx2 were encoded by different genomic locus. As the first
      analyzed genomic structure of PtTrxs in crustaceans, two introns with
      microsatellites were found in the open reading frame region of these genes.
      Quantitative real-time PCR analysis revealed the mRNA expression of PtTrx1
      transcripts were mainly detected in gill, while, PtTrx2 in eyestalk and gill. The
      temporal expression levels of PtTrxs transcripts in haemocytes showed different
      expression patterns after challenge with Vibrio alginolyticus, Micrococcus luteus
      and Pichia pastoris. These results together indicate that PtTrxs should be
      involved in the responses to pathogen challenge of P. trituberculatus.

PMID- 22365992
TI  - Transcriptomic analysis of the host response to early stage salmonid alphavirus
      (SAV-1) infection in Atlantic salmon Salmo salar L.
AB  - Salmon pancreas disease, caused by salmonid alphavirus (SAV) of the family
      Togaviridae, is an economically important disease affecting farmed Atlantic
      salmon (Salmo salar L.) in Scotland, Norway, and Ireland. The virus causes
      characteristic lesions in the pancreas, heart, kidney and skeletal muscle of
      infected fish. The mechanisms responsible for the pathology and the immune
      responses elicited in infected Atlantic salmon are not fully understood. A
      microarray-based study was therefore performed to evaluate the host
      transcriptomic response during the early stages of an experimentally-induced SAV
      1 infection. Atlantic salmon parr were injected intra-peritoneally with viral
      cell culture supernatant or cell culture supernatant without virus. RNA,
      extracted from head kidney sampled from infected and control fish at 1, 3 and 5
      days post-injection (d.p.i.), was interrogated with the 17 k TRAITS/SGP cDNA
      microarray. The greatest number of significantly differentially expressed genes
      was recorded at 3 d.p.i., mainly associated with immune and defence mechanisms,
      including genes involved in interferon I pathways and Major Histocompatibility
      Complex Class I and II responses. Genes associated with apoptosis and cellular
      stress were also found to be differentially expressed between infected and
      uninfected individuals, as were genes involved in inhibiting viral attachment and
      replication. The microarray results were validated by follow-on analysis of eight
      genes by real-time PCR. The findings of the study reflect mechanisms used by the
      host to protect itself during the early stages of SAV-1 infection. In particular,
      there was evidence of rapid induction of interferon-mediated responses similar to
      those seen during mammalian alphavirus infections, and also early involvement of
      an adaptive immune response. This study provides essential knowledge to assist in
      the development of effective control and management strategies for SAV-1
      infection.

PMID- 22365993
TI  - PEANUT experiment in NQR spectroscopy for I=3/2.
AB  - The experiment with phase inversion and phase-inverted echo-amplitude detected
      nutation (PEANUT) was introduced in the nuclear quadrupole resonance (NQR).
      Formulas were obtained describing the NQR (I=3/2) experiment. Exemplary
      experiments are provided confirming the predicted particularities of the PEANUT
      spectra in NQR Cl-35. It is proposed to apply the method for the purpose of
      determination the asymmetry parameter of the electric field gradient (EFG) tensor
      in powders with the help of the analysis of PEANUT interferograms. Application of
      two-dimensional PEANUT experiments, in which the nutation frequencies correlate
      with the resonance NQR frequencies, can substantially simplify the interpretation
      of complex spectra.

PMID- 22365994
TI  - Effects of kirenol on bovine type II collagen-induced rat lymphocytes in vivo and
      in vitro.
AB  - OBJECTIVE: To investigate the effect of kirenol on bovine type II collagen (CII)
      specific lymphocytes in vivo and in vitro, and explore the mechanism of kirenol
      induced immunosuppression in antigen-specific lymphocytes. METHODS: Twenty-four
      Wistar rats were randomized into control group, collagen-induced arthritis (CIA)
      model group, kirenol group (2 mg/kg), and prednisolone group (2 mg/kg). After CII
      injection, the rats in the latter two groups received intragastric administration
      of kirenol and prednisolone for 30 days, and the spleens and draining lymph nodes
      of the rats were harvested to prepare single cell suspensions for measurement of
      the cytokine levels using ELISA. In the in vitro experiment, the lymphocytes from
      the control rats, with or without 20 ug/ml CII treatment in the presence of 0-80
      ug/ml kirenol, were evaluated for cell proliferation and apoptosis using [(3)H]
      thymidine incorporation and flow cytometry, respectively. RESULTS: Compared with
      those in CIA group, IFN-gamma and TNF-alpha production was significantly reduced
      in splenocyte culture supernatant of kirenol group (P<0.05 and P<0.01,
      respectively), and the level of IL-10 and IL-4 was up-regulated (P<0.05 and
      P<0.01, respectively); IFN-gamma and TNF-alpha secretion by the cultured lymph
      node cells (LNCs) significantly decreased (P<0.05 and P<0.001, respectively) and
      IL-10 and IL-4 production increased (P<0.05, P<0.001) in kirenol group. In the in
      vitro experiment, kirenol treatment caused obvious suppression of CII-induced LNC
      proliferation and dose-dependently induced antigen-specific apoptosis of the
      splenocytes and LNCs. CONCLUSION: Kirenol treatment reduces pro-inflammatory
      cytokine secretion, increases anti-inflammatory cytokine production, inhibits 
      cell proliferation and induces apoptosis of CII-specific lymphocytes in vitro,
      suggesting the potential of kirenol as an immunosuppressant.

PMID- 22365995
TI  - [Effect of lentivirus-mediated nestin gene silencing on metastatic potential of
      human melanoma cell line UACC903 in vitro].
AB  - OBJECTIVE: To study the effect of lentivirus-mediated RNA interference (RNAi) of
      nestin on the metastatic potential of human melanoma cell line UACC903. METHODS:
      A lentiviral vector for RNAi targeting the coding region of human nestin mRNA
      (nestin-RNAi-LV) and another control vector containing a nonsense sequence were
      constructed. The vectors were transfected into UACC903 cells, and nestin
      expression in the cells was detected by RT-PCR, immunofluorence assay and Western
      blotting. The invasive ability and migration of the transfected UACC903 cells was
      evaluated using Transwell and scrape assay, respectively. Fluorescence assay was
      used to examine the expressions of E-cadherin, N-cadherin and beta-catenin in the
      cells. RESULTS: The lentiviral vector nestin-RNAi-LV was constructed
      successfully. Compared with the control vector, nestin-RNAi-LV resulted in
      obviously reduced expression of nestin mRNA and protein, lowered migration
      ability of UACC903 cells, and reduced cell adhesion  and invasiveness (P<0.05).
      CONCLUSION: Lentivirus-mediated nestin RNAi can specifically inhibit nestin
      expression to cause decreased cell migration and invasiveness of human melanoma
      cell line UACC903.

PMID- 22365996
TI  - [Endothelial dysfunction induced by high glucose is associated with decreased ATP
      binding cassette transporter G1 expression].
AB  - OBJECTIVE: To investigate the role of ATP-binding cassette transporter G1 (ABCG1)
      in endothelial dysfunction induced by high glucose. METHODS: Human aortic
      endothelial cells (HAECs) were incubated in the presence of 5.6 or 30 mmol/L
      glucose for 24-72 h with or without a 2-h pretreatment with the LXR agonist 22(R)
      hydroxycholesterol. Real-time PCR and Western blotting were used to measure the
      mRNA and protein expressions of ABCG1; the intracellular cholesterol efflux and
      endothelial nitric oxide synthase (eNOS) activity were measured by scintillation
      counting. RESULTS: High glucose time-dependently suppressed ABCG1 expression and
      cholesterol efflux to HDL in HAECs. High glucose also decreased eNOS activity.
      ABCG1 down-regulation induced by high glucose, along with decreased cholesterol
      efflux and eNOS activity, was abolished by treatment of the cells with the LXR
      agonist. CONCLUSION: Endothelial dysfunction induced by high glucose is
      associated with decreased ABCG1 expression.

PMID- 22365997
TI  - [Multi-slice computed tomography for diagnosis of mucinous cystic neoplasms and
      serous cystadenomas of the pancreas].
AB  - OBJECTIVE: To assess the value of multi-slice computed tomography (MSCT) in the
      diagnosis and differential diagnosis of  pancreatic mucinous cystic neoplasms and
      serous cystadenoma. METHOD: The MSCT images were reviewed for 19 pathologically
      confirmed cases of pancreatic mucinous cystadenomas and 13 cases of pancreatic
      serous cystadenomas (n=13) treated in our center between July, 2003 and December,
      2009. The CT features were analyzed including the tumor location, contour,
      dimension of the largest cyst, cystic wall, septation, presence of calcification,
      solid component, pancreatic atrophy, main pancreatic duct dilatation, and lesion
      margins. RESULTS: Significant differences were found between the two groups in
      lesion diameter  (P=0.009), cyst distribution of the largest cyst (>2 cm)
      (P=0.01), and the presence of solid component (P=0.02). CONCLUSION: MSCT can be
      of important value in the diagnosis and differential diagnosis of  pancreatic
      mucinous cystic neoplasms and serous cystadenomas.

PMID- 22365998
TI  - [Liver CT image segmentation using statistical shape model based on statistical
      and specific information].
AB  - We propose an effective algorithm for accurate 3D segmentation of CT liver images
      based on statistical and specific information. We present a new intensity model
      which combines patient-specific intensity information of boundary with the
      statistical information for liver segmentation. Compared to the traditional
      methods, our approach not only produces excellent segmentation accuracy, but also
      increases the robustness.

PMID- 22365999
TI  - [Effect of 25-hydroxyvitamin D(3) on vitamin D receptor expression and
      distribution in human bronchial epithelial cells in vitro].
AB  - OBJECTIVE: To evaluate the effect of 25-hydroxyvitamin D(3) on the expression and
      distribution of vitamin D receptor in normal human bronchial epithelial cells.
      METHODS: MTT assay was used to assess the viability of human airway epithelial
      cell line 16HBE following a 24-h exposure to different concentrations of 25
      hydroxyvitamin D(3). Real-time quantitative PCR, Western blotting, and
      immunofluorescence assay were used to observe the expression and distribution of
      vitamin D receptor in the cells following the exposure. RESULTS: Compared with
      the control cells, 16HBE cells exposed to different concentrations of 25
      hydroxyvitamin D(3) exhibited no significantly increase in the expression or
      distribution of vitamin D receptor. CONCLUSION: The influence of 25
      hydroxyvitamin D(3) on bronchial epithelial cells might be independent of the
      expression and translocation of vitamin D receptor.

PMID- 22366000
TI  - [Effect of retinoic acid on alkaline phosphatase expression in rat adipose
      derived stem cells].
AB  - OBJECTIVE: To investigate whether adipose-derived stem cells (ADSCs) induced by
      retinoic acid (RA) in vitro express primordial germ cell marker alkaline
      phosphatase (ALP) and vasa. METHODS: ADSCs were isolated from adult female SD
      rats and cultured in vitro. The third passage of ADSCs was identified by
      adipogenic differentiation, osteogenic differentiation and cell surface marker
      detection. The ADSCs were treated with 1*10(-5), 1*10(-6), or 1*10(-7) mol/L RA
      for 7 or 14 days, and the cellular expression of ALP was detected. vasa mRNA
      expression in ADSCs treated with 1*10(-5) mol/L RA for 7 days was detected using
      RT-PCR. RESULTS: The OD value of ADSCs treated with 1*10(-5), 1*10(-6), or 1*10(
      7) mol/L RA was 0.59?0.04, 0.27?0.07, and 0.15?0.03 after a 7-day treatment, and
      was 0.42?0.02, 0.34?0.01, and 0.19?0.02 after a 14-day treatment, respectively,
      demonstrating significantly enhanced ALP expression in RA-treated ADSCs compared
      with that in the control cells (0.07?0.01 and 0.07?0.01 at 7 and 14 days,
      respectively, P<0.01). The ADSCs showed a negative vasa mRNA expression after
      1*10(-5) mol/L RA treatment for 7 days. CONCLUSION: RA-induced ADSCs express ALP,
      a marker of primordial germ cells, but does not express the primordial germ cell
      marker vasa.

PMID- 22366001
TI  - [Role of Slit-Robo signaling in the proliferation of human mucoepidermoid
      carcinoma Mc3 cells].
AB  - OBJECTIVE: To study the role of Slit-Robo signaling in the proliferation of human
      mucoepidermoid carcinoma Mc3 cells. METHODS: We measured the expressions of Slit2
      and Robo1 proteins in human mucoepidermoid carcinoma Mc3 cells using
      immunohistochemistry and flow cytometry. To test the role of Slit-Robo signaling
      in the proliferation of the cells, we treated the cells with the monoclonal
      antibody R5 against Robo1 receptor extracellular domain and observed the changes
      in the cell proliferation by cell counting and colonogenic assay; the expression
      of proliferating cell nuclear antigen (PCNA) in the cells following the treatment
      was measured with flow cytometry. RESULTS: Treatment of Mc3 cells with the
      monoclonal antibody R5 caused significantly suppressed cell growth and
      proliferation and obviously lowered the expression of PCNA. CONCLUSION: Slit-Robo
      signaling can suppress the proliferation of Mc3 cells possibly by up-regulating
      the expression of PCNA.

PMID- 22366002
TI  - [Preliminary application of an improved Demons deformable registration algorithm
      in tumor radiotherapy].
AB  - OBJECTIVE: To validate the efficiency of an improved Demons deformable
      registration algorithm and evaluate its application in registration of the
      treatment image and the planning image in image-guided radiotherapy (IGRT).
      METHODS: Based on Brox's gradient constancy assumption and Malis's efficient
      second-order minimization algorithm, a grey value gradient similarity term was
      added into the original energy function, and a formula was derived to calculate
      the update of transformation field. The limited Broyden-Fletcher-Goldfarb-Shanno
      (L-BFGS) algorithm was used to optimize the energy function for automatic
      determination of the iteration number. The proposed algorithm was validated using
      mathematically deformed images, physically deformed phantom images and clinical
      tumor images. RESULTS: Compared with the original Additive Demons algorithm, the
      improved Demons algorithm achieved a higher precision and a faster convergence
      speed. CONCLUSION: Due to the influence of different scanning conditions in
      fractionated radiation, the density range of the treatment image and the planning
      image may be different. The improved Demons algorithm can achieve faster and more
      accurate radiotherapy.

PMID- 22366003
TI  - [Construction and sequence analysis of recombinant HCV-1b replicon by replacing
      NS5A region].
AB  - OBJECTIVE: To construct the recombinant HCV-1b replicon by replacing NS5A region
      using serum samples from patients with chronic hepatitis C (CHC) in South China
      and explore the biological characteristics of NS5A protein in response to
      antiviral therapy. METHODS: The on-off plasmid containing the cutting sites of
      the restriction endonucleases MIu I and Bcl I was designed based on the backbone
      of robust HCV 1b replicon. The full-length fragments of HCV NS5A were amplified
      from different CHC patients by RT-PCR and cloned into pMD-18 vector, followed by
      sequence analysis of amino acid mutation of ISDR, PKRBD, V3 and IRRDR within the
      NS5A region. If the amplicon obtained contained no MIu I or Bcl I cutting sites,
      the NS5A fragment was re-amplified using primers containing the cutting sites and
      inserted into the replicon for replacement. RESULTS: The full-length fragments of
      NS5A were obtained successfully from CHC patients. The core region of ISDR-V3 of
      NS5A was replaced in the HCV replicon plasmid and showed correct sequences. The
      amino acid mutations of ISDR and PKRBD within NS5A were more frequent in patients
      with sustained viral response (SVR) than those without SVR. A high variability in
      the amino acid sequence was observed in both IRRDR and V3 regions. CONCLUSION:
      The plug-in type recombinant HCV replicon for replacement of NS5A region in the
      virus from CHC patients has been successfully constructed, which provides a basis
      for further investigation of the biological characteristics of NS5A protein, the
      mechanisms of interferon-resistance, and antiviral therapy of difficult-to-treat
      CHC.

PMID- 22366004
TI  - [Influences of D-galactosamine and lipopolysaccharide on liver tissue
      regeneration and repair in mice with partial hepatectomy].
AB  - OBJECTIVE: To observe the effect of D-galactosamine (D-GaIN) and
      lipopolysaccharide (LPS) on liver tissue regeneration and repair in mice
      following liver injury induced by partial hepatectomy. METHODS: A total of 40
      male BALB/c mice were randomly assigned into 2 equal groups to receive
      intraperitoneal injections of D-GaIN (500 mg/kg) plus LPS (50 ug/kg, given 1 h
      later) or two doses of saline 24 h prior to 1/3 hepatectomy. The liver
      weight/body weight (LW/BW) ratio and liver regeneration rate were observed at
      different time points after partial hepatectomy. Liver cell injury was assessed
      using HE staining, hepatocyte proliferation evaluated with BrdU staining, and the
      oval cell proliferation observed with immunohistochemistry. RESULTS: In mice
      receiving saline injection, the liver volume was nearly restored 9 days after
      partial hepatectomy, while in mice with D-GaIN and LPS injections, the liver
      failed to recover the normal volume even at 14 days, showing a significant
      difference in the liver regeneration rate between them [(22.6?105.93)% vs
      (9.49?32.55)%, P<0.001]. Significant degenerative changes of the hepatic cells
      were found in D-GaIN/LPS-treated group, while only mild inflammatory reaction was
      observed in saline-treated group after partial hepatectomy. Obvious hepatocyte
      proliferation was observed at day 7 in saline-treated group but not in D-GaIN/LPS
      treated group. Oval cell proliferation in the portal area occurred 3 days after
      partial hepatectomy in D-GaIN/LPS-treated group. CONCLUSION: D-GaIN and LPS can
      obviously inhibit hepatocyte regeneration after liver injury in mice. D-GaIN and
      LPS combined with partial hepatectomy can induce oval cell proliferation.

PMID- 22366005
TI  - [Construction of SDF-1P2G54, a specific antagonist of CXCR4].
AB  - OBJECTIVE: To obtain a specific antagonist of CXCR4, SDF-1P2G54 by mutating SDF-1
      second proline (P) into glycin (G) and removing the alpha-helix of its C
      terminal. METHODS: SDF-1p2g54 gene amplified by PCR was inserted into the vector
      pET-30a (+) and transformed into Escherichia coli (E. coli) strain BL21. After
      IPTG induction of E. coli, the expressed recombinant protein was purified with
      nickel-affinity chromatography column under denaturing conditions and refolded
      with gradient dilution and ultra-filtration. The chemotactic effect of SDF-1P2G54
      on Jurkat cells and its antagonistic effect against SDF-1 were determined by
      transwell assay; flow cytometry was used to assay the ability of SDF-1P2G54 to
      induce calcium influx and CXCR4 internalization in MOLT4 cells. RESULTS: The
      recombinant protein SDF-1P2G54 completely lost the functions to activate CXCR4 or
      to induce transmembrane migration of Jurkat cells and calcium influx in MOLT4
      cells, but maintained a high affinity to CXCR4. SDF-1P2G54 effectively inhibited
      the chemotactic effect of wild-type SDF-1 to Jurkat cells, and induced rapid
      CXCR4 internalization in MOLT4 cells. CONCLUSION: SDF-1P2G54 is a new antagonist
      of CXCR4 with a potential value as an effective inhibitor of HIV-1 infection,
      cancer metastasis or other major diseases.

PMID- 22366006
TI  - [Effect of human serum extracted by two different methods on human dermal
      fibroblast growth in vitro].
AB  - OBJECTIVE: To explore the optimal method for extracting human serum that retains
      rich growth factors. METHODS: Human serum was isolated by centrifugation of
      coagulated whole blood or by Anitua's method, and the concentrations of PDGF-AB
      and transforming growth factor-beta1 (TGF-beta1) in the serum samples were
      measured. Human dermal fibroblasts were cultured in the presence of 10% feral
      bovine serum or 10% human serum obtained, and the cell morphology, viability and
      proliferative activity of the cells were evaluated. RESULTS: The fibroblasts grew
      well in all the media with good viability. The cells cultured in the presence of
      human serum isolated by centrifugation of coagulated whole blood, which had the
      richest content of growth factors, showed the greatest cell number and cell
      viability among the groups (P<0.05), a result consistent with the growth curve
      and MTT curve. CONCLUSION: Centrifugation of coagulated whole blood retains high
      contents of growth factors in human serum to better promote cell growth, and is
      simple, cost-effective and most efficient for serum isolation.

PMID- 22366007
TI  - [Effect of a recombinant lentiviral vector carrying hepatocyte nuclear factor 6
      gene on migration and invasion abilities of SW620 cells].
AB  - OBJECTIVE: To construct a recombinant lentiviral vector that stably express
      hepatocyte nuclear factor 6 (HNF6) in colorectal cancer cell line and examine its
      effects on the invasive ability of SW620 cells. METHODS: The lentiviral vector
      pLeno-DCE-HA-HNF6 was constructed and transfected into 293T cells. The
      supernatant containing the lentivirus particles was harvested to determine the
      virus titer. A stable cell line was established by infecting SW620 cells with the
      lentivirus particles, and the transfection efficiency was examined by
      fluorescence microscopy and flow cytometry. The invasion ability of the
      transfected SW620-HNF6 cells was assessed by wound healing and transwell assays.
      RESULTS: The recombinant lentiviral vector was correctly constructed and verified
      by sequencing. SW620-HNF6 cell line with stable HNF6 expression was established
      successfully, and the transfection efficiency reached 82.3%. Western blotting and
      quantitative PCR demonstrated significantly upregulated HNF6 expression in SW620
      HNF6 cells, which showed obviously suppressed invasive ability in wound healing
      and transwell assays. CONCLUSION: We have successfully established a colorectal
      cancer cell line SW620-HNF6 stably expressing HNF6, which shows a lowered
      migration activity in vitro.

PMID- 22366008
TI  - [Effect of hyperoxia exposure on the function of N9 microglia in vitro].
AB  - OBJECTIVE: To observe the effect of normobaric hyperoxia exposure on the
      functions of N9 microglia and explore the underlying mechanism of hyperoxia
      induced immature brain injury. METHODS: N9 microglial cells were exposed to 900
      ml/L O(2) for 2, 6, 12, 24 or 48 h, and the cell apoptotic rate was assessed
      using flow cytometry. The intracellular oxidative stress was measured using a
      fluorescent DCFH-DA probe, and the expression of Toll-like receptor 4 (TLR4) mRNA
      was detected using RT-PCR. Interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha) concentrations in the supernatant of the cell cultures were
      tested with ELISA following the exposures. TLR4 protein expression was observed
      using immunofluorescence staining. RESULTS: Significant cell apoptosis was
      detected after oxygen exposures for 12-24 h. Accumulation of reactive oxygen
      species (ROS) were detected after a 2-h exposure. After prolonged hyperoxia
      exposure, TLR4 expression and IL-1beta and TNF-alpha levels significantly
      increased in the cells. CONCLUSION: Hyperoxia exposure activates TLR4 signaling
      pathway in N9 microglial cells in vitro, leading to massive production of ROS, IL
      1beta, and TNF-alpha and thus triggering cell apoptosis.

PMID- 22366009
TI  - [Effects of interleukin-17 on murine pulmonary fibroblast proliferation,
      transformation and collagen synthesis].
AB  - OBJECTIVE: To investigate the effects of interleukin-17 (IL-17) on the
      proliferation, transformation and collagen synthesis of the lung fibroblasts in
      mice with bleomycin-induced pulmonary fibrosis. METHODS: In a mouse model of
      pulmonary fibrosis established by intratracheal administration of 5 mg/kg
      bleomycin, the dynamic expressions of IL-17/IL-17 receptor (IL-17R) mRNAs were
      detected by RT-PCR. At 14 days following bleomycin administration, the pulmonary
      fibroblasts were isolated, cultured and identified. MTT assay was used to assess
      the proliferation of the pulmonary fibroblasts in response to IL-17 treatment at
      different concentrations, and RT-PCR and Western blotting were employed to
      examine the mRNA and protein expressions of alpha-smooth muscle actin (alpha-SMA)
      and types I and III collagen. RESULTS: IL-17/IL-17R mRNA levels were increased
      obviously in the pulmonary fibroblasts of rats with pulmonary fibrosis, and the
      highest expressions occurred at 14 days following bleomycin administration.
      Exogenous IL-17, at the optimal concentration of 50 ng/ml, significantly promoted
      the proliferation of the pulmonary fibroblasts in primary culture and obviously
      increased alpha-SMA expression and types I and III collagen synthesis in the
      fibroblasts. CONCLUSION: IL-17 can promote the proliferation, transformation, and
      collagen synthesis of the pulmonary fibroblasts from rats with bleomycin-induced
      pulmonary fibrosis.

PMID- 22366010
TI  - [Anxiolytic effect of Anshenfang in rats].
AB  - OBJECTIVE: To assess the anxiolytic effect of Anshenfang granules (ASF), a
      compound traditional Chinese medicinal preparation, on anxiety in rats and the
      mechanism of its actions. METHODS: Male Wistar rats with anxiety induced by
      chronic emotional stress were randomized to receive treatments with diazepam or
      ASF at high, medium or low doses. The behavioral changes of the rats were
      evaluated using plus-maze test, after which the rats in normal control group,
      model group, and medium AFS dose group were sacrificed to measure the hippocampal
      contents of glutamic acid and gamma-aminobutyric acid (GABA) using high
      performance liquid chromatography (HPLC); immunohistochemistry was employed to
      evaluate the expressions of GABAA receptor and N-methyl-D-aspartate receptor 1
      (NMDAR1). RESULTS: Plus-maze test showed obvious anxiety behaviors in the model
      group, which were significantly meliorated by diazepam and ASF, especially at the
      medium dose. Hippocampal glutamate levels increased and GABA decreased
      significantly in the model group, and such changes were obviously attenuated, by
      comparable amplitudes, by treatments with diazepam and medium-dose ASF. The model
      group showed significantly diminished GABAA receptor-positive cells and increased
      NMDAR1-positive cells, which were improved by diazepam and ASF at the medium
      dose. CONCLUSION: ASF produces strong anxiolytic effect in rats by increasing the
      content of GABA in the brain, enhancing GABAA receptor expression, reducing
      glutamic acid content, and decreasing NMDAR1 expression.

PMID- 22366011
TI  - [Heterogeneity of mitochondrial DNA in black and white hair of patients with type
      2 diabetes].
AB  - OBJECTIVE: To detect the heterogeneity of mitochondrial DNA (mtDNA) in black and
      white hair of patients with type 2 diabetes. METHODS: MtDNA was extracted from
      the hair shaft of the patients to amplify two target DNA fragment from mtDNA
      coding region and control region using PCR. The differences in the heterogeneity
      in the target DNA fragment was analyzed between diabetic patients and the control
      group with denaturing high-performance liquid chromatography (DHPLC). RESULTS: In
      the control subjects and diabetic patients, the mtDNA heterogeneity in the black
      hair was 3% and 10% in 20-45 year-old groups and 9% and 17% in 45-70 year-old
      groups, as compared to 9%, 20%, 21%, and 40% in the white hair, respectively. The
      mtDNA heterogeneity in the black and white hair was both higher in the diabetic
      patients than in the control subjects of the same age group, and was also higher
      in older age subgroups in both control and diabetic groups (P<0.05). The white
      hair mtDNA showed a significantly higher heterogeneity than the black hair mtDNA
      in the two age groups of diabetic patients and in 45-70 year-old control group
      (P<0.05). CONCLUSION: The mtDNA heterogeneity in the hair increases in type 2
      diabetic patients and show an association with aging.

PMID- 22366012
TI  - [Comparison of neuroprotective effects of hypothermia induced by different
      methods in rats with early cerebral ischemia].
AB  - OBJECTIVE: To compare the neuroprotective effects of intracarotid cold saline
      infusion (ICSI), ice cap and systemic cooling in rats with early cerebral
      ischemia. METHODS: SD rats were randomly divided into model group, ice cap group,
      systemic cooling group and ICSI group (n=13). Cerebral ischemia was induced by
      middle cerebral artery occlusion (MCAO) for 2 h. In the 3 hypothermic groups, the
      target temperature of 33-34 degrees celsius; was achieved and maintained for 20
      min. In each group, the neurological scores were recorded at 48 h after the
      reperfusion, and the brains were removed for measuring the infarct size using
      2,3,5-triphenyltetrazolium chloride staining. The brain water contents and serum
      levels of neuron-specific enolase (NSE), S100beta and matrix metalloproteinase 9
      (MMP9) were also measured. RESULTS: Compared with the model group, the ice cap,
      systemic cooling and ICSI groups all showed significantly reduced infarct size by
      27.4% (P<0.05), 47.6% (P<0.01) and 61.6% (P<0.01), respectively. The systemic
      cooling and ICSI groups, but not the ice cap group, had significantly lower brain
      water contents than the model group (P<0.05). Among the 3 hypothermic methods,
      only ICSI significantly improved the neurological scores (P<0.05) and reduced
      serum NSE and S100beta levels (P<0.05). CONCLUSION: Of the 3 hypothermic groups,
      ICSI has the best neuroprotective effects, and systemic cooling produces better
      effect than ice cap in rats with ischemic stroke.

PMID- 22366013
TI  - [Effects of erythropoietin pretreatment on pro-and anti-inflammatory balance in
      rats with severe acute pancreatitis].
AB  - OBJECTIVE: To evaluate the effect of pretreatment with erythropoietin (EPO) on
      disordered pro- and anti- inflammatory balance in rats with severe acute
      pancreatitis (SAP) and explore the underlying mechanisms. METHODS: Ninety healthy
      male SD rats were randomized equally into sham-operated group, SAP group and EPO
      pretreatment group. SAP model was induced in the latter two groups by retrograde
      injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In
      EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before
      SAP, and normal saline was administered in the other two groups. Serum amylase
      activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time
      points after the operation. The translocation and activation of nuclear factor
      kappaB (NF-kappaB) in the pancreatic tissue was detected using immunofluorescence
      staining, and pancreatic pathologies were evaluated. RESULTS: Compared with SAP
      group, EPO group showed a markedly decreased activation rate of NF-kappaB after
      SAP except for 12 h (P<0.05), significantly decreased serum amylase activity at
      3, 6, and 12 h (P<0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P<0.05),
      whereas serum IL-10 underwent no significant changes. The rats in EPO group
      showed an obviously milder pancreatic pathology than those in SAP group at 6, 12,
      and 24 h (P<0.05). CONCLUSION: EPO can effectively inhibit NF-kappaB activation
      by regulating the inflammatory mediators and restoring the pro-and anti
      inflammatory balance to alleviate SAP in rats.

PMID- 22366014
TI  - [Effect of tetrandrine on bax, bcl-2 and TGF-beta2 mRNA expressions in cultured
      human Tenon's capsule fibroblasts].
AB  - OBJECTIVE: To investigate the effect of tetrandrine (Tet) on the expression of
      bax, bcl-2, and transforming growth factor-beta2 (TGF-beta2) mRNA in cultured
      human fibroblasts of Tenon's capsules (TCFS) and explore its possible mechanism.
      METHODS: The third passage of TCFS cultured in vitro were exposed to 1*10(-5)
      mol/L Tet for 24 h, and real-time fluorescence quantitative PCR was used to
      detect the changes in the expressions of bax, bcl-2, and TGF-beta2 mRNA. RESULTS:
      The expression level of bax mRNA was obviously higher, while bcl-2 and TGF-beta2
      mRNA levels were significantly lower in Tet-treated TCFS than those in the
      control cells (P<0.05). CONCLUSION: Tet can  inhibit  the proliferation of TCFS
      possibly by reducing the expressions of bcl-2 and TGF-beta2 mRNA, enhancing the
      expression of bax mRNA and inducing cell apoptosis, suggesting its potential in
      preventing fibrous scar formation after glaucoma filtration surgery.

PMID- 22366015
TI  - [Intratumor injection of  recombinant  attenuated salmonella carrying
      Mycobacterium tuberculosis heat shock protein 70 and herpes simplex virus
      thymidine kinase genes to suppress murine melanoma growth].
AB  - OBJECTIVE: To study the effection of suppression murine melanoma growth by
      Intratumor injection of recombinant  attenuated salmonella carrying heat shock
      protein 70 and herpes simplex virus thymidine kinase genes. METHODS: Plasmids
      PCMV-mtHSP70-IRES-TK  were electro-transferred into salmonella typhimurium SL7207
      to construct recombinant salmonella typhimurium. In vivo, Recombinant bacteria
      were  injected into the mouse melanoma and the antitumor effection was observed.
      The survival period was recorded and safety analysis for this vaccine in each
      group. RESULTS: In vivo, the mtHSP70/HSV-tk recombinant bacteria can suppress
      tumor growth significantly and extend survival. After recombinant Salmonella,
      10(9) CFU/mL, was administered as an intratumoral injection, No diarrhea  were
      observed. During therapy, body weight did not change markedly. CONCLUSION:
      Results of the animal experiment suggests intratumor injection of recombinant
      attenuated salmonella typhimurium containing mtHSP70 and HSV-tk genes, has
      targeting ability against B16 tumor cell and could significantly inhibit tumor
      growth .

PMID- 22366016
TI  - [Optimization of a compound prescription for treating liver fibrosis].
AB  - OBJECTIVE: To optimize a compound prescription for treatment of liver fibrosis
      with an improved therapeutic effect and low toxicity. METHODS: In rat models of
      liver fibrosis induced by thioacetamide (TAA), the optimized prescription was
      screened based on a uniform design with 2-factor 5-level table using Uniform
      Design 3.0 software and tested using liver content of Hyp as the screening index.
      To verify the efficacy of the optimized prescription, the rat models of liver
      fibrosis were randomized  into normal control group, model group, colchicine
      group and optimized prescription group, and the changes of hepatic Hyp content,
      serum HA, ALT, AST, and ALB levels, and the pathology liver fibrosis were
      observed after corresponding treatments. RESULTS: The optimized prescription,
      which contained 70 mg/kg glycyrrhizin and 70 mg/kg matrine, showed a significant
      therapeutic effect against liver fibrosis in rats (Plt;0.05), and the effect was
      equivalent to that of colchicine (P>0.05). CONCLUSION: Uniform design is a
      valuable method in prescription optimization. The optimized compound prescription
      of matrine and glycyrrhizin has a significant effect in inhibiting liver
      fibrosis.

PMID- 22366017
TI  - [A pedigree analysis of pulmonary embolism caused by compound heterozygous
      mutations of protein C].
AB  - OBJECTIVE: To study the molecular pathogenesis of protein C (PC) deficiency in a
      patient with pulmonary embolism and in his family members. METHODS:
      Anticoagulated blood samples were collected from the proband and his family
      members to detect PC, PS and AT activities. PC antigen level was measured using
      ELISA. The genomic DNA was extracted to amplify all the 9 exons and their
      flanking sequences of PC gene using PCR, and the PCR products were sequenced. The
      mutated exons identified were amplified and sequenced for the other family
      members. RESULTS: The proband and his parents and sister were identified as
      carriers of PC gene mutation, which led to type II PC deficiency. Sequencing of
      the proband's PC gene showed two heterozygous point mutations in exon 3 (G5540A)
      and exon 7 (C10230T) to cause compound heterozygous mutations of PC E29K and PC
      R147W, which were inherited from his father and mother, respectively. His sister
      was a heterozygote of PC R147W. CONCLUSION: The proband is a compourd
      heterozygous mutations carrier of PC E29K and PC147W. PC E29K is a novel PC
      mutation, and PC R147W is a reported PC gene mutation seen in patients with type
      II hereditary PC deficiency and recurrent thrombosis.

PMID- 22366018
TI  - [Correlation between HIV antibody and sexual behaviors of men who have sex with
      men in Guangzhou in 2010].
AB  - OBJECTIVE: To investigate the correlation between human immunodeficiency virus
      (HIV) and the sexual behaviors of men who have sex with men (MSM) in Guangzhou in
      2010. METHODS: Anti-HIV antibody was detected in the volunteers undergoing HIV
      tests in the year 2010, and the differences in the sexual role, education, use of
      condom and complicated infection of syphilis were analyzed among these subjects.
      RESULTS: A total of 1526 MSM volunteered to participate in the investigation,
      among whom 87 (5.70%) were confirmed to have HIV infection. The positivity rate
      of HIV infection was 3.54%, 7.14% and 6.70% in subjects reporting active anal
      copulation, passive anal copulation, and both, respectively, showing a
      significant difference in respect of the sexual role (chi(2)=6.450, P=0.040). The
      positivity rate also differed significantly among married, unmarried and divorced
      subjects (9.45%, 4.92%, and 4.17%, respectively; chi(2)=7.184, P=0.028). The
      positivity rate was 21.31% among those with syphilis, significantly higher than
      the rate in those without syphilis (5.06%, chi(2)=25.770, P<0.001). Use of condom
      was not associated with a significant reduction of HIV positivity rate (P>0.05).
      CONCLUSION: The high anti-HIV positivity rate among MSM in Guangzhou indicates a
      high risk of unsafe sexual behaviors, especially anal copulations. The anal
      copulation receivers, often young and have a lower rate of condom use, constitute
      a high-risk group of HIV transmission.

PMID- 22366019
TI  - [Extracorporeal shock wave lithotripsy for lower urinary tract stones:
      complications and the contributing factors].
AB  - OBJEVTIVE: To analyze the complications of extracorporeal shock wave lithotripsy
      (ESWL) for treatment of lower urinary tract stones and identify the factors
      contributing to the complications. METHODS: We retrospectively analyzed the
      postoperative complications of ESWL in 83 patients with lower urinary tract
      stones and their association with the patients' age, height, body weight, body
      mass index (BMI), stone features, shock wave times, and shock wave energy.
      RESULTS: Of the 83 cases treated with ESWL, 72.3% (60 cases) showed gross
      hematuria, 27.7% (23 cases) complained of pain, and 25.3% (21 cases) had both
      pain and gross hematuria. None of the patients reported vomiting, skin rash,
      flatulence, gastrointestinal bleeding or other complications. Patients with
      postoperative gross hematuria, pain, and both had significantly greater stone
      length, stone width and more shock body times than those without these
      complications (P<0.01 or P<0.05). Patients with gross hematuria had significantly
      lower height than those without complications (P<0.05). CONCLUSION: The common
      complications of ESWL for lower urinary tract stones include hematuria and pain.
      The patient's height, stone length, stone width and shock times are important
      factors contributing to these postoperative complications.

PMID- 22366020
TI  - [Effect of CO(2) pneumoperitoneum on renal function in rats].
AB  - OBJECTIVE: To evaluate the effects of different CO(2) pneumoperitoneum conditions
      on renal function in rats and provide experimental evidence for improving renal
      graft function after transplantation. METHODS: SD rats were randomized into 10
      groups (n=12) and subject to CO(2) pneumoperitoneum at different pressures (0.67,
      1.33 and 2.0 kPa) for 60 or 120 min. Serum urea nitrogen (BUN), creatinine (Cr)
      and N-acetyl-beta-D-glocosaminidase (NAG) levels were detected after
      pneumoperitoneum. RESULTS: As the pressure and time of pneumoperitoneum
      increased, the renal function deteriorated gradually, showing significant
      differences between the groups (P<0.05). CONCLUSION: Increased pressure and
      prolonged duration of CO(2) pneumoperitoneum causes impairment of the renal
      function, suggesting the necessity of reducing the operative time and lowering
      the pressure of pneumoperitoneum when harvesting renal graft in living donors.

PMID- 22366021
TI  - [Effects of Bushen Huoxue Fang on rat cardiac fibroblast proliferation and
      collagen production in vitro].
AB  - OBJECTIVE: To investigate the effects of Bushen Huoxue Fang on the proliferation
      of rat cardiac fibroblasts and collagen production in the cells. METHODS: Rat
      cardiac fibroblasts were isolated and cultured in DMEM containing 10% (group A)
      or 20% (group B) or no (group C) serum from rats treated with Bushen Huoxue Fang,
      with cells cultured in DMEM containing 10% FBS as the control (group D). After 72
      h of cell culture, the proliferation of the fibroblasts was detected using CCK-8
      kit, and collagen mRNA and protein expressions were examined using RT-PCR and
      Western blotting, respectively. RESULTS: Compared with that in groups C and D,
      the cell proliferation decreased significantly in groups A and B, and especially
      in the latter (P<0.05). RT-PCR demonstrated significant reductions of the mRNAs
      of type 1 and 3 collagens in groups A and B (P<0.05), and their protein levels
      were also significantly lowered (P<0.05). CONCLUSION: Bushen Huoxue Fang can
      effectively inhibit the proliferation of rat cardiac fibroblasts and reduced
      collagen type 1 and 3 productions in the cells in vitro.

PMID- 22366022
TI  - [Determination of melamine by high-performance liquid chromatography-mass
      spectrometry in urinary calculi].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography-mass
      spectrometry (LC/MS)-based method for efficient determination of melamine in
      urinary calculi in children taking melamine-contaminated formula milk powder.
      METHODS: LC/MS was employed to determine the contents of melamine in urinary
      calculi surgically removed from 17 children with a history of taking melamine
      contaminated milk powder and in 4 samples of uric acid stone from adults. The
      positive ionization mode of electro-spray ionization source was used, and the
      limit of melamine determination was 0.1 mg/kg. RESULTS: No melamine was detected
      in the 4 uric acid stone samples from adults. Melamine was detected in 4 samples
      of urinary calculi from the 17 children, with the concentration ranging from 0.8
      to 64 mg/lkg. CONCLUSION: LC/MS is simple and effective for detecting melamine in
      urinary calculi, which is helpful to the treatment and follow-up.

PMID- 22366023
TI  - [Cardiac conductive disease with atrial fibrillation in a Chinese pedigree and
      evaluation of the treatments].
AB  - OBJECTIVE: To investigate the clinical characteristics of a Chinese pedigree with
      cardiac conductive disease complicated by atrial fibrillation and the therapeutic
      effect of the treatments. METHODS: All the family members including the proband
      were screened with routine examination, electrocardiography, echocardiograpy,
      Holter recording, chest X-ray, blood biochemistry tests and autoantibody test.
      The proband received dual chamber pacemaker implantation combined with oral
      amiodarone treatment for 3 months. The patient was monitored for thyreoid
      function and chest X-ray during the treatments, and was followed up for another 3
      months. RESULTS: Clinical evidence of organic heart disease was found in none of
      the family members. The proband showed recurrent dizziness and chest distress,
      which exacerbated after exercise, and ECG showed atrial fibrillation and severe A
      V block. The proband's uncle was found to have atrial fibrillation and III degree
      A-V block after a syncope episode at the age of 30, and received a pacemaker
      treatment. Her grandpa died from a heart attack without detailed clinical
      documentations. No other family members showed abnormal ECG or a history of any
      heart events. The proband's condition was improved by treatments, after which ECG
      and Holter recording showed pace rhythm without atrial fibrillation. CONCLUSION:
      Cardiac conductive disease with atrial fibrillation can present in one family,
      and can be managed effectively and safely with implantation of dual chamber
      pacemaker combined with oral amiodarone.

PMID- 22366024
TI  - [Clinicopathological analysis of clear cell meningioma].
AB  - We present two cases of clear cell meningioma (CCM) in the intracranial and
      intraspinal region with anaplastic features. On histological examination, both
      the tumors exhibited unusual anaplastic appearances with nuclear pleomorphism, a
      high mitotic activity and necrosis, which were different from classical CCMs. The
      tumor cells were immunoreactive to epithelial membrane antigen (EMA) and vimentin
      with a high MIB-1 index of 40%. Total excision of the tumors was performed in
      both cases. The male patient was found to have local recurrence and lateral
      ventricle metastasis 3 months after the total excision. We reviewed the
      clinicopathological features, disagnosis and prognosis of the disease. We
      recommend that postoperative adjuvant radiotherapy or chemotherapy be performed
      after total tumor excision, and MRI scan every 3-6 months is mandatory during the
      initial follow-up period.

PMID- 22366025
TI  - [Diagnosis and treatment of inflammatory myofibroblastic tumor of the chest].
AB  - OBJECTIVE: To explore the causes, clinic diagnosis, treatment and prognosis of
      inflammatory myofibroblastic tumor (IMT) of the chest. METHODS: The clinical data
      of 12 patients with IMT were retrospectively analyzed including 9 male and 3
      female patients aged 36 to 81 years (mean 60.08 years). Five patients underwent
      pulmonary lobectomy and mediastinal lymph node dissection, 1 had partial
      lobectomy, 1 had mediastinal tumor resection and costectomy, and 2 received
      conservative treatment. RESULTS: All the surgical patients recovered after
      surgery without lymph node metastasis detected by pathological examinations. In
      the follow-up lasting for 2 months to 5 years, no recurrence or metastasis
      occurred in these cases. In the 2 cases having conservative treatment, the tumor
      remained unchanged in one case at 3 month of follow-up and disappeared in the
      other case. CONCLUSION: IMT in the chest is a rare benign tumor with a low
      incidence rate and malignancy. Pathological examination is reliable for definite
      diagnosis. Surgical operation is the primary therapeutic approach. All IMT
      patients should be closely followed up after the treatment.

PMID- 22366026
TI  - Does vitamin D protect against DNA damage?
AB  - Vitamin D is a secosteroid best known for its role in maintaining bone and muscle
      health. Adequate levels of vitamin D may also be beneficial in maintaining DNA
      integrity. This role of vitamin D can be divided into a primary function that
      prevents damage from DNA and a secondary function that regulates the growth rate
      of cells. The potential for vitamin D to reduce oxidative damage to DNA in a
      human has been suggested by clinical trial where vitamin D supplementation
      reduced 8-hydroxy-2'-deoxyguanosine, a marker of oxidative damage, in colorectal
      epithelial crypt cells. Studies in animal models and in different cell types have
      also shown marked reduction in oxidative stress damage and chromosomal
      aberrations, prevention of telomere shortening and inhibition of telomerase
      activity following treatment with vitamin D. The secondary function of vitamin D
      in preventing DNA damage includes regulation of the poly-ADP-ribose polymerase
      activity in the DNA damage response pathway involved in the detection of DNA
      lesions. It is also able to regulate the cell cycle to prevent the propagation of
      damaged DNA, and to regulate apoptosis to promote cell death. Vitamin D may
      contribute to prevention of human colorectal cancer, though there is little
      evidence to suggest that prevention of DNA damage mediates this effect, if real.
      Very limited human data mean that the intake of vitamin D required to minimise
      DNA damage remains uncertain.

PMID- 22366027
TI  - Characterisation of vaccine-induced, broadly cross-reactive IFN-gamma secreting T
      cell responses that correlate with rapid protection against classical swine fever
      virus.
AB  - Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid
      onset of protection, but the lack of a serological test that can differentiate
      vaccinated from infected animals limits their application in CSF outbreaks. Since
      immunity may precede antibody responses, we examined the kinetics and specificity
      of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine
      and challenged after five days with a genotypically divergent CSFV isolate.
      Vaccinated animals displayed virus-specific IFN-gamma responses from day 3 post
      challenge, whereas, unvaccinated challenge control animals failed to mount a
      detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as
      the cellular source of IFN-gamma. IFN-gamma responses showed extensive cross
      reactivity when T cells were stimulated with CSFV isolates spanning the major
      genotypes. To determine the specificity of these responses, T cells were
      stimulated with recombinant CSFV proteins and a proteome-wide peptide library
      from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2
      and NS3 proteins. Finally, IFN-gamma was shown to exert potent antiviral effects
      on CSFV in vitro. These data support the involvement of broadly cross-reactive T
      cell IFN-gamma responses in the rapid protection conferred by the C-strain
      vaccine and this information should aid the development of the next generation of
      CSFV vaccines.

PMID- 22366028
TI  - Laser Doppler assessment of dermal circulatory changes in people with coronary
      artery disease.
AB  - BACKGROUND: Dermal microcirculation provides an easily accessible vasculature bed
      which can be used to assess endothelial mediated vasodilatation. We studied and
      compared microcirculatory changes in response to acetylcholine iontophoresis
      (ACh), local heating of the skin and reactive hyperaemia in patients with
      coronary artery disease (CAD). METHODS AND RESULTS: Forty eight patients with CAD
      were studied and compared with 25 age and sex matched control subjects.
      Vasodilatory changes in the dermal microcirculation were assessed in response to
      ACh iontophoresis, local heating of the skin and reactive hyperaemia using a
      laser Doppler flowmeter (LDF). RESULTS: Body mass index (BMI) and systolic BP
      were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured
      as absolute in agreement with our previous publish results) in response to ACh
      iontophoresis, local heating of the skin and reactive hyperaemia, in healthy
      controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units
      (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with
      CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was
      significantly higher in patients with CAD, 14.1+/-4.0 vs 10.9+/-1.7s; p=0.001.
      There was a small but significant positive correlation between the perfusion
      change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On
      ROC curve analysis, perfusion changes with heating had higher sensitivity and
      specificity in discriminating patients with CAD from the healthy controls with an
      area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of
      77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41%
      sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88%
      sensitivity and 60% specificity). CONCLUSION: Vasodilatation in the dermal
      microcirculation measured by the three techniques is attenuated in patients with
      coronary artery disease. Local heating of the skin is a better discriminator of
      patients with CAD than ACh iontophoresis and reactive hyperaemia.

PMID- 22366029
TI  - The rate of Q(x)->Q(y) relaxation in bacteriochlorophylls of reaction centers
      from Rhodobacter sphaeroides determined by kinetics of the ultrafast carotenoid
      bandshift.
AB  - Transient absorption changes induced by excitation of isolated reaction centers
      (RCs) from Rhodobacter sphaeroides with 600nm laser pulses of 20fs (full width at
      half maximum) were monitored in the wavelength region of 420-560nm. The spectral
      features of the spectrum obtained are characteristic for an electrochromic band
      shift of the single carotenoid (Car) molecule spheroidene, which is an integral
      constituent of these RCs. This effect is assigned to an electrochromic bandshift
      of Car due to the local electric field of the dipole moment formed by electronic
      excitation of bacteriochlorophyll (BChl) molecule(s) in the neighborhood of Car.
      Based on the known distances between the pigments, the monomeric BChl (B(B)) in
      the inactive B-branch is inferred to dominate this effect. The excitation of B(B)
      at 600nm leads to a transition into the S(2) state (Q(x) band), which is followed
      by rapid internal conversion to the S(1) state (Q(y) band), thus leading to a
      change of strength and orientation of the dipole moment, i.e., of the electric
      field acting on the Car molecule. Therefore, the time course of the
      electrochromic bandshift reflects the rate of the internal conversion from S(2)
      to S(1) of B(B). The evaluation of the kinetics leads to a value of 30fs for this
      relaxation process. This article is part of a Special Issue entitled:
      Photosynthesis Research for Sustainability: from Natural to Artificial.

PMID- 22366030
TI  - Purification and biochemical characterization of a lysosomal alpha-fucosidase
      from the deuterostomia Asterias rubens.
AB  - In vertebrates, mannose 6-phosphate receptors [MPR300 (Mr 300 kDa) and MPR46 (Mr
      46 kDa)] are highly conserved transmembrane glycoproteins that mediate transport
      of lysosomal enzymes to lysosomes. Our studies have revealed the appearance of
      these putative receptors in invertebrates such as the molluscs and deuterostomes.
      Starfish tissue extracts contain several lysosomal enzyme activities and here we
      describe the affinity purification of alpha-fucosidase. The purified enzyme is a
      glycoprotein that exhibited a molecular mass of ~56 kDa in SDS-PAGE under
      reducing conditions. It has also cross-reacted with an antiserum to the mollusc
      enzyme suggesting antigenic similarities among the two invertebrate enzymes. LC
      MS/MS analysis of the proteolytic peptides of the purified enzyme in combination
      with de novo sequencing allowed us to do partial amino acid sequence
      determination of the enzyme. These data suggest that this invertebrate enzyme is
      homologous to the known mammalian enzyme. The purified enzyme exhibited a mannose
      6-phosphate dependent interaction with the immobilized starfish MPR300 protein.
      Our results demonstrate that the lysosomal enzyme targeting pathway is conserved
      even among the invertebrates.

PMID- 22366031
TI  - Direct observation of the initial process of Ostwald ripening using spherical
      aberration-corrected transmission electron microscopy.
AB  - We study in situ behavior of platinum single atoms on amorphous carbon (a-carbon)
      using a spherical aberration-corrected transmission electron microscope (AC-TEM).
      Diffusion of single atoms, bi-atoms, clusters (<1 nm) and nanoparticles (<3 nm)
      was recorded in the same image with a time resolution of 1 s, and such diffusion
      matches the expected mechanism of Ostwald ripening, which was seen on these
      samples. In situ AC-TEM shows promise for dynamical observation of single atom
      diffusion, which is important for understanding nanosized catalysts and ceramic
      sintering processes. We apply in situ AC-TEM to image platinum (Pt) nanoparticles
      on a-carbon, which is a model catalyst system for the real Pt electrode catalysts
      using alloys and core-shell structures supported on carbon/oxide composite
      materials in the proton exchange membrane fuel cell.

PMID- 22366032
TI  - Hepatic ultrastructure in a neonatal piglet model of intestinal failure
      associated liver disease (IFALD).
AB  - This study was designed to evaluate liver disease in neonatal piglets with
      surgical short bowel syndrome causing intestinal failure with partial parenteral
      nutrition dependence. The short bowel piglets had 75% surgical resection of
      distal small intestine, including all ileum and cecum, and were compared with
      sham controls, without resection, and to healthy sow-reared controls. After 18
      days of combined parenteral and enteral nutrition in short bowel and sham
      piglets, liver tissue was collected for quantitative and semi-quantitative
      histological and ultrastructural evaluation. The short bowel piglets developed
      biochemical and histological cholestasis, not observed in sham and control
      piglets. Ultrastructural examination revealed bile canaliculus dilation with bile
      plugging, microvillus flattening and disappearance, but without abnormalities of
      the pericanalicular zone. Interestingly, these data are similar to bile
      canaliculus changes seen in human neonates with IFALD supporting an initial
      consideration of this model to elucidate the pathogenesis of IFALD.

PMID- 22366033
TI  - Subcellular localization and putative role of VPS13A/chorein in dopaminergic
      neuronal cells.
AB  - Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disorder
      caused by loss of function mutations in the vacuolar protein sorting 13 homolog A
      (VPS13A) gene encoding chorein. Although a deficiency in chorein function leads
      to apoptosis of striatal neurons in ChAc model mouse, its detailed subcellular
      localization and physiological role remain unclear. In this study, we produced
      two anti-chorein polyclonal antibodies and examined the intracellular
      localization of endogenous chorein in neuronal cells. Immunocytochemically,
      chorein was observed in the termini of extended neurites and partially
      colocalized with synaptotagmin I in differentiated PC12 cells. Subcellular
      localization analysis by sucrose density gradient fractionation showed that
      chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which
      contain dopamine. In addition, PC12 cells stably expressing carboxyterminal
      fragment of chorein increased K(+)-induced dopamine release. Taken together,
      these results suggest that chorein is involved in exocytosis of DCV.

PMID- 22366034
TI  - Dimerization is essential for HAb18G/CD147 promoting tumor invasion via MAPK
      pathway.
AB  - HAb18G/CD147 is a transmembrane glycoprotein of the immunoglobulin superfamily
      (IgSF) and is reported to be correlated with invasion and metastasis of many
      cancers. The crystal structure of HAb18G/CD147 ectodomain has shown that it can
      form homodimers in crystal. However, the functional significance of HAb18G/CD147
      dimerization remains unclear. In the present study, guided by the crystal
      structure, we performed extensive mutational and functional studies to identify
      residues critical for dimerization and molecular function of HAb18G/CD147.
      Fourteen mutants were purified and evaluated for their ability to form dimers in
      solution and in living cells. Subsequent functional validation revealed that K63E
      and S193A mutants, which disrupted CD147 dimerization both in solution and in
      living cells, showed clearly dominant-negative effects on MAPK activation, MMP2
      induction and invasiveness in tumor cells. Taken together, the present study
      provides mutational and functional evidences demonstrating for the first time the
      functional importance of CD147 dimerization and its direct correlation with
      invasion and metastasis of tumor cells.

PMID- 22366035
TI  - Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a
      common ancestral zinc protein.
AB  - Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin
      (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase.
      Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex
      constituents, as a zinc-binding protein, along with BoNT. A protein structure
      classification database search indicated that BoNT and NTNHA share a similar
      domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT
      coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma
      mass spectrometry analysis demonstrated that every single NTNHA molecule contains
      a single zinc atom. This is the first demonstration of a zinc atom in this
      protein, as far as we know. However, the NTNHA molecule does not possess any
      known zinc-coordinating motif, whereas all BoNT serotypes possess the classical
      HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K
      C-L-I-K-X(35)-D sequence common among all NTNHA serotype molecules appears to
      coordinate a single zinc atom. These findings lead us to propose that NTNHA and
      BoNT may have evolved distinct functional specializations following their
      branching out from a common ancestral zinc protein.

PMID- 22366036
TI  - A novel role of brain-type ACS4 isotype in neuronal differentiation.
AB  - Acyl-CoA synthetase (ACS4) is an arachidonate preferring acyl-CoA synthetase and
      has been shown to play an important role in lipid metabolism. Although
      arachidonate and decosahexanoate play a key role in lipid metabolism and in the
      brain, the mechanisms of its action are still not clearly understood. In this
      study, we identified brain-type ACS4 mRNA by 5'-RACE. We also confirmed that the
      mRNA in TT2 ES cells encoded a novel ACS4 protein, which contains 41 amino acids
      at its N-terminus. Furthermore, we found that ACS4 proteins were up-regulated in
      PC-12 cell by stimulation with nerve growth factor (NGF). Importantly, knockout
      of ACS4 in ES cells markedly attenuated neuronal differentiation induced by NGF
      and all-trans retinoic acids (RA). These results indicate that the ACS4 protein
      specifically expressed in brain plays an important role in arachidonate
      metabolism and neuronal differentiation in the brain.

PMID- 22366037
TI  - Quantitative analysis of extension-torsion coupling of actin filaments.
AB  - Actin filaments have a double-helix structure consisting of globular actin
      molecules. In many mechanical cellular activities, such as cell movement,
      division, and shape control, modulation of the extensional and torsional dynamics
      of the filament has been linked to regulatory actin-binding protein functions.
      Therefore, it is important to quantitatively evaluate extension-torsion coupling
      of filament to better understand the actin filament dynamics. In the present
      study, the extension-torsion coupling was investigated using molecular dynamics
      simulations. We constructed a model for the actin filament consisting of 14 actin
      subunits in an ionic solvent as a minimal functional unit, and analyzed
      longitudinal and twisting Brownian motions of the filament. We then derived the
      expected value of energy associated with extension and torsion at equilibrium,
      and evaluated the extension-torsion stiffness of the filament from the thermal
      fluctuations obtained from the MD simulations. The results demonstrated that as
      the analyzed sampling-window duration was increased, the extension-torsion
      coupling stiffness evaluated on a nanosecond scale tended to converge to a value
      of 7.6*10(-11) N. The results obtained from this study will contribute to the
      understanding of biomechanical events, under mechanical tension and torque,
      involving extension-torsion coupling of filaments.

PMID- 22366038
TI  - Thermospermine is not a minor polyamine in the plant kingdom.
AB  - Thermospermine is a structural isomer of spermine, which is one of the polyamines
      studied extensively in the past, and is produced from spermidine by the action of
      thermospermine synthase encoded by a gene named ACAULIS5 (ACL5) in plants.
      According to recent genome sequencing analyses, ACL5-like genes are widely
      distributed throughout the plant kingdom. In Arabidopsis, ACL5 is expressed
      specifically during xylem formation from procambial cells to differentiating
      xylem vessels. Loss-of-function mutants of ACL5 display overproliferation of
      xylem vessels along with severe dwarfism, suggesting that thermospermine plays a
      role in the repression of xylem differentiation. Studies of suppressor mutants of
      acl5 that recover the wild-type phenotype in the absence of thermospermine
      suggest that thermospermine acts on the translation of specific mRNAs containing
      upstream open reading frames (uORFs). Thermospermine is a novel type of plant
      growth regulator and may also serve in the control of wood biomass production.

PMID- 22366039
TI  - Establishing an emergency department syndromic surveillance system to support the
      London 2012 Olympic and Paralympic Games.
AB  - BACKGROUND: The London 2012 Olympic and Paralympic Games is a mass gathering
      event that will present a major public health challenge. The Health Protection
      Agency, in collaboration with the College of Emergency Medicine, has established
      the Emergency Department Sentinel Syndromic Surveillance System (EDSSS) to
      support the public health surveillance requirements of the Games. METHODS: This
      feasibility study assesses the usefulness of EDSSS in monitoring indicators of
      disease in the community. Daily counts of anonymised attendance data from six
      emergency departments across England were analysed by patient demographics (age,
      gender, partial postcode), triage coding and diagnosis codes. Generic and
      specific syndromic indicators were developed using aggregations of diagnosis
      codes recorded during each attendance. RESULTS: Over 339,000 attendances were
      recorded (26 July 2010 to 25 July 2011). The highest attendances recorded on
      weekdays between 10:00 and 11:00 and on weekends between 12:00 and 13:00. The
      mean daily attendance per emergency department was 257 (range 38-435). Syndromic
      indicators were developed including: respiratory, gastrointestinal, cardiac,
      acute respiratory infection, gastroenteritis and myocardial ischaemia.
      Respiratory and acute respiratory infection indicators peaked during December
      2010, concomitant with national influenza activity, as monitored through other
      influenza surveillance systems. CONCLUSIONS: The EDSSS has been established to
      provide an enhanced surveillance system for the London 2012 Olympics. Further
      validation of the data will be required; however, the results from this initial
      descriptive study demonstrate the potential for identifying unusual and/or severe
      outbreaks of infectious disease, or other incidents with public health impact,
      within the community.

PMID- 22366040
TI  - A case of paediatric simulated pneumothorax.

PMID- 22366041
TI  - Assessment of adverse drug event recognition by emergency physicians in a French
      teaching hospital.
AB  - OBJECTIVES: The frequency and the severity of drug-related visits in emergency
      department (ED) make the improvement of adverse drug event (ADE) recognition a
      crucial issue. As part of a research project aiming to improve the diagnosis and
      the management of ADEs in ED, the authors conducted a pilot study whose primary
      objective was to assess ADE recognition by emergency physicians. METHODS: The
      patients presenting to the ED were included at randomised time periods between 1
      October 2007 and 31 March 2008 in this prospective cross-sectional study. The
      primary outcome was the frequency of ADEs that were attributed to a medication
      related problem by the emergency physician. RESULTS: A total of 423 patients met
      the inclusion criteria, of which 95 experienced an ADE (22.5%; 95% CI 18.6% to
      26.7%). Emergency physicians correctly attributed 33 of these cases (34.7%; 95%
      CI 25.3% to 45.2%) to a medication-related problem. Of the 28 cases in which the
      ADE was considered as a 'direct drug effect' (29.5%; 95% CI 20.6% to 39.7%), 16
      were correctly identified by emergency physicians (57.1%; 95% CI 37.2% to 75.5%).
      Of the 67 cases in which the ADE was considered as a 'drug involvement in a
      multifactorial pathological condition' (70.5%; 95% CI 60.3% to 79.4%), 17 were
      correctly attributed (25.4%; 95% CI 15.5% to 37.5%). CONCLUSIONS: ADEs are
      frequent in EDs and are not well recognised by emergency physicians, especially
      when the drug is involved in a multifactorial pathological condition.

PMID- 22366042
TI  - Correlates of willingness to participate in microbicide research among African
      Americans.
AB  - The objective of the present article is to identify predictors of willingness to
      participate (WTP) in microbicide trials among African Americans. A total of 595
      participants completed a survey on WTP in microbicide trials and predictors of
      WTP. Significant associations were observed for relationships of greater WTP with
      female gender, greater HIV risk, lower mistrust of research, and knowing someone
      with HIV/AIDS. An interaction revealed HIV risk was positively associated with
      WTP for women only. Accurate knowledge of the Tuskegee Syphilis Study was
      associated with greater WTP. These predictors may be employed in microbicide
      trials to enhance African American participation.

PMID- 22366043
TI  - Increased numbers but functional defects of CD56+CD3+ cells in lung cancer.
AB  - CD56+ T cells were studied in samples of peripheral blood from small-cell lung
      cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients compared with
      healthy controls. Relative numbers of CD56+CD3+ cells were increased in NSCLC (P
      = 0.001) and SCLC (P = 0.002) compared with normal subjects but their ability to
      respond to activation by up-regulating CD25 or producing IFN-gamma were both
      significantly impaired. Expression of the killer-immunoglobulin-like receptor
      CD158a was significantly lower on CD56+CD3+ cells in SCLC than controls and also
      in early stage compared with late stage NSCLC patients. Mean levels of CD158e
      were higher in NSCLC patients than controls. CD158e levels on CD56+CD3+ cells
      were increased in the presence of its ligand HLA-Bw4 compared with controls.
      Although the precise role of CD56+CD3+ cells is not clear, they appear to be
      functionally impaired in lung cancer, which may have implications for a reduction
      of direct or indirect anti-tumour responses.

PMID- 22366044
TI  - Regulatory T cells form stable and long-lasting cell cluster with myeloid
      dendritic cells (DC).
AB  - Regulatory T cells (Treg) with the capacity to suppress T-cell proliferation
      exert various effects on T cell function. In addition, Treg have been shown to
      modulate the phenotype and function of antigen-presenting cells (APC) including
      dendritic cells (DC), B cells and monocytes/macrophages. However, the specific
      mechanism(s) of how Treg affect APC have not been entirely identified so far. In
      this study, we analyzed the interaction of human Treg and effector T cells (Teff)
      with peripheral blood myeloid and monocyte-derived dendritic cells in vitro. A
      strong tendency for cell cluster formation between Treg and DC was observed,
      which was dependent on the adhesion molecules ICAM-1, LFA-3 and ICAM-3. In
      addition, Treg were found to express higher levels of LFA-1, LFA-2, LFA-3 and
      ICAM-3 both before and after activation with anti-CD3 antibodies. Using in vitro
      live cell imaging, we were further able to show that Treg-DC cell clusters, in
      contrast to Teff-DC clusters, were stable and long lasting. Co-cultures of DC
      with Treg diminished the up-regulation of activation induced costimulatory
      molecule expression on DC, and further reduced the production of tumor necrosis
      factor alpha and stimulated the production of IL-4. In summary, our data indicate
      that Treg-DC cluster formation might enable Treg to modulate phenotypic and
      functional characteristics of DC and help to constrain Teff activation.

PMID- 22366045
TI  - Induction of immunological tolerance in chickens inoculated with xenogeneic
      antigens at a late stage of embryonic development.
AB  - To induce immunotolerance, chicken embryos were inoculated with BSA on embryonic
      incubation day (EID) 20. All hatched chickens were challenged with BSA four times
      at 10-day intervals, beginning at 3 weeks of age. Serum anti-BSA antibodies were
      analyzed and our results show that immunotolerance was obtained in the group
      micro-injected with 1 mg of BSA. We administered BSA labeled with 2,4
      dinitrophenyl (DNP) into blood vessels on EID 20 and detected the distribution of
      BSA by immunohistochemistry. Our results show that DNP-BSA was located in the
      bursal cortex, thymus and spleen. PBMCs were separated on the seventh day after
      the fourth immunization to determine the effect of treatments on lymphocytes and
      the percentage of CD4(+) T cells among the CD3(+) T cell population. Results from
      these experiments show that there was an influence on T lymphocyte proliferation,
      with the number of CD4(+) T cells in the tolerance group significantly increased.
      To determine whether tolerance was induced in B cells, 2,4,6-trinitrophenyl
      coupled to BSA (TNP-BSA) was inoculated into birds, followed by detection of anti
      TNP antibodies in the serum. Immunological tolerance in B cells was not observed
      following these experiments. The results from our study demonstrate that
      immunological tolerance was induced in T cells when 1 mg of BSA was micro
      injected on EID 20.

PMID- 22366046
TI  - Fever control using external cooling in septic shock: a randomized controlled
      trial.
AB  - RATIONALE: Fever control may improve vascular tone and decrease oxygen
      consumption, but fever may contribute to combat infection. OBJECTIVES: To
      determine whether fever control by external cooling diminishes vasopressor
      requirements in septic shock. METHODS: In a multicenter randomized controlled
      trial, febrile patients with septic shock requiring vasopressors, mechanical
      ventilation, and sedation were allocated to external cooling (n = 101) to achieve
      normothermia (36.5-37 degrees C) for 48 hours or no external cooling (n = 99).
      Vasopressors were tapered to maintain the same blood pressure target in the two
      groups. The primary endpoint was the number of patients with a 50% decrease in
      baseline vasopressor dose after 48 hours. MEASUREMENTS AND MAIN RESULTS: Body
      temperature was significantly lower in the cooling group after 2 hours of
      treatment (36.8 +/- 0.7 vs. 38.4 +/- 1.1 degrees C; P < 0.01). A 50% vasopressor
      dose decrease was significantly more common with external cooling from 12 hours
      of treatment (54 vs. 20%; absolute difference, 34%; 95% confidence interval [95%
      CI], -46 to -21; P < 0.001) but not at 48 hours (72 vs. 61%; absolute difference,
      11%; 95% CI, -23 to 2). Shock reversal during the intensive care unit stay was
      significantly more common with cooling (86 vs. 73%; absolute difference, 13%; 95%
      CI, 2 to 25; P = 0.021). Day-14 mortality was significantly lower in the cooling
      group (19 vs. 34%; absolute difference, -16%; 95% CI, -28 to -4; P = 0.013).
      CONCLUSIONS: In this study, fever control using external cooling was safe and
      decreased vasopressor requirements and early mortality in septic shock.

PMID- 22366047
TI  - Subclinical interstitial lung disease: why you should care.
AB  - The widespread use of high-resolution computed tomography in clinical and
      research settings has increased the detection of interstitial lung abnormalities
      (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers,
      ILA were present in about 1 of every 12 high-resolution computed tomographic
      scans; however, the long-term significance of these subclinical changes remains
      unclear. Studies in families affected with pulmonary fibrosis, smokers with
      chronic obstructive pulmonary disease, and patients with inflammatory lung
      disease have shown that asymptomatic and undiagnosed individuals with ILA have
      reductions in lung volume, functional limitations, increased pulmonary symptoms,
      histopathologic changes, and molecular profiles similar to those observed in
      patients with clinically significant interstitial lung disease (ILD). These
      findings suggest that, in select at-risk populations, ILA may represent early
      stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding
      this topic is motivated by our poor understanding of the inciting events and
      natural history of ILD, coupled with a lack of effective therapies. In this
      perspective, we outline past and current research focused on validating
      radiologic, physiological, and molecular methods to detect subclinical ILD. We
      discuss the limitations of the available cross-sectional studies and the need for
      future longitudinal studies to determine the prognostic and therapeutic
      implications of subclinical ILD in populations at risk of developing clinically
      significant ILD.

PMID- 22366049
TI  - Staphylococcus aureus (MSSA) and MRSA (CC398) isolated from post-mortem samples
      from pigs.
AB  - There are many reports on the occurrence of Livestock Associated Methicilline
      resistant Staphylococcus aureus (LA-MRSA, CC398) in healthy pigs. There are
      however, very few reports of LA-MRSA being associated with pathological lesions
      in pigs. With this study we try to find the answers to the questions: (1) how
      often is S. aureus found in post-mortem material from pigs, (2) how many of these
      isolates are methicillin resistant, (3) are these equally distributed over the
      years? Here we report the isolation of MRSA and of methicillin sensitive S.
      aureus (MSSA) from samples derived from post-mortem examinations at the Animal
      Health Service in The Netherlands in the period from 2003 through October 2008.
      The MSSA and MRSA described here were isolated from 159 pathological lesions and
      from 7 submissions of aborted foetuses derived from a total of 116 animals,
      representing 103 submissions coming from 92 different herds. This is
      approximately 0.5% of all pigs submitted for post mortem examination in those
      years. The proportion of pigs from which S. aureus (both MSSA and MRSA) was
      isolated from, did not increase over the years. MSSA (N=97) and LA-MRSA CC398
      (N=18) were present mainly in (peri)arthritis in over 30% of all cases, but were
      also isolated from internal organs such as lung, brain, spleen, kidneys, heart,
      indicating septicaemia. Remarkably, one non-CC398 MRSA (ST1) was isolated in a
      joint and a kidney of one pig. This isolate was resistant to 5 out of 6
      antimicrobials tested. There was no significant difference in the type of lesions
      in which LA-MRSA was found compared to MSSA. The number of antimicrobials these
      isolates were resistant to, increased rapidly after 2004. LA-MRSA was isolated
      for the first time in 2005 and then again in 2007 and 2008, suggesting that this
      is an emerging pathogen. However, due to changes in the panel of antimicrobials
      used to test S. aureus for antimicrobial susceptibility in 2005 and 2007, the
      possibility exists that we may have missed some MRSA isolates. LA-MRSA isolates
      are resistant to at least three but sometimes five out of six antimicrobials
      tested. All isolates were susceptible to the combination of
      Trimethoprim/Sulfamethaxol.

PMID- 22366048
TI  - Increased H1N1 infection rate in children with asthma.
AB  - RATIONALE: The 2009 H1N1 flu appeared to cause more severe cold symptoms during
      the 2009-2010 flu season. OBJECTIVES: We evaluated H1N1 infections during peak
      viral season in children with and without asthma to determine whether the H1N1
      infectivity rate and illness severity were greater in subjects with asthma.
      METHODS: One hundred and eighty children, 4-12 years of age, provided eight
      consecutive weekly nasal mucus samples from September 5 through October 24, 2009,
      and scored cold and asthma symptoms daily. Viral diagnostics were performed for
      all nasal samples. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty-one
      children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal
      samples. The incidence of H1N1 infection was significantly higher in children
      with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95%
      confidence interval, 1.8-9; P < 0.001), but rates of human rhinovirus infection
      (90% each) and other viral infections (47 vs. 41%) were similar. In children with
      asthma, there was a nonsignificant trend for increased loss of asthma control
      during H1N1 infections compared with human rhinovirus infections (38 vs. 21%;
      odds ratio, 2.6; 95% confidence interval, 0.9-7.2; P = 0.07). CONCLUSIONS: During
      peak 2009 H1N1 flu season, children with asthma were infected almost twice as
      often with H1N1 compared with other respiratory viruses. H1N1 infection also
      caused increased severity of cold symptoms compared with other viral infections.
      Given the increased susceptibility of children with asthma to infection, these
      findings reinforce the need for yearly influenza vaccination to prevent
      infection, and raise new questions about the mechanism for enhanced
      susceptibility to influenza infection in asthma.

PMID- 22366050
TI  - Tolerability of antiepileptic drugs: can we determine differences?
AB  - Patient tolerability of adverse effects is integral to successful treatment.
      Although standard antiepileptic drugs (AEDs) are well tolerated by many patients,
      the promise of newer AEDs has been the potential for diminished burden of
      problems with similar seizure control. This report reviews the prevalence of
      systemic and neurological adverse effects reported in clinical trials of AED
      monotherapy. A central finding in this report was the unidirectional higher
      prevalence of selected adverse effects from standard compared with newer AEDs. A
      system of questioning every patient at every visit to elicit information may be
      helpful when balancing benefit-to-risk ratio of individualized therapy during
      everyday practice.

PMID- 22366051
TI  - The ketogenic diet as a treatment option in adults with chronic refractory
      epilepsy: efficacy and tolerability in clinical practice.
AB  - The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that is
      used as a treatment for patients with difficult-to-control epilepsy. The present
      study assesses the efficacy and tolerability of the KD as an add-on therapy in
      adults with chronic refractory epilepsy. 15 adults were treated with the
      classical diet or MCT diet. During a follow-up period of 1 year we assessed
      seizure frequency, seizure severity, tolerability, cognitive performance, mood
      and quality of life (QOL). We found a significant reduction in seizures among the
      patients who followed the diet at least 1 year (n=5). Of these 5 patients, 2 had
      a reduction between 50 and 90%. Analyzing the study months separately, we found a
      seizure reduction of >=50% in 26.6% of the patients during at least 1 month of
      treatment. Common side-effects were gastrointestinal disorders, loss of weight
      and fatigue. There was a considerable, non-significant improvement found in mood
      and QOL scores. Improvements were independent of reduction in seizure frequency,
      indicating that the effects of the KD reach further than seizure control.

PMID- 22366052
TI  - Sleep disturbances in juvenile myoclonic epilepsy: a sleep questionnaire-based
      study.
AB  - Sleep and epilepsy share a complex pathophysiological association. Juvenile
      myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect
      of seizures could have therapeutic implications in terms of sleep disturbances
      and seizure control. This study aimed to analyze the effect of epilepsy on sleep
      in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age-
      and gender-matched controls were recruited into this prospective, hospital-based,
      case-control study after informed consent and screening for inclusion criteria.
      They underwent a detailed clinical assessment, electroencephalogram (EEG) and
      neuroimaging, and were administered validated sleep questionnaires, which
      included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index
      (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups
      had identical numbers of males and females (M: F=22: 28), without any significant
      difference in the age and body mass index (BMI). The clinical profile of JME was
      similar to published literature while the prevalence of EEG abnormalities was
      less compared to similar studies. The mean ESS and PSQI scores and the number of
      subjects with abnormal scores on one or both questionnaires were significantly
      more in patients. Patients had a higher prevalence of sleep disturbances,
      insomnia and excessive daytime somnolence. No significant seizure- or treatment
      related factors influencing sleep could be identified. This study, the first of
      its kind, revealed that patients with JME have significant sleep disturbances
      characterized by excessive daytime sleepiness and disturbed night sleep, despite
      adequate medications and good seizure control. The role of VPA in the genesis of
      these symptoms needs clarification.

PMID- 22366053
TI  - Morningness and eveningness: when do patients take their antiepileptic drugs?
AB  - Almost one-third of epilepsy patients continue to have seizures despite adequate
      drug treatment. Chronotherapy (based on dynamic changes in drug pharmacology and
      disease-related processes) could be a promising treatment option. We aimed to
      explore whether different circadian types adjust administration times of anti
      epileptic drugs (AEDs) as a step in exploring chronotherapeutic possibilities. We
      performed a questionnaire-based study to compare behavior of different circadian
      types in relation to times of taking drugs. Circadian type was determined by the
      Morningness-Eveningness Questionnaire. Results clearly show that morning types
      are taking their AEDs significantly earlier than do evening types on free days.
      Times of taking AEDs in the morning on work days also differ significantly
      between morning and evening types. Regardless of circadian type, drugs on free
      days are taken later than on working days. In conclusion, our study shows that
      patients adapt times of taking medication to their circadian type.

PMID- 22366054
TI  - Decision time and response accuracy in a conditional motor learning task are
      impaired independently in unilateral temporal lobe-resected patients.
AB  - Learning and memory of declarative knowledge and relational information are
      dependent on the integrity of medial temporal lobe (MTL). Numerous studies
      suggest that left lobectomy impairs verbal memory while right lobectomy impairs
      non-verbal memory. In order to instrumentally quantify material-specific memory
      impairment after temporal lobe excision, we compared, using a computerized
      conditional motor associative learning task, patients with surgically treated
      drug-resistant temporal lobe epilepsy to age-matched controls. We enrolled seven
      epileptic patients with left (LTR), seven with right (RTR) temporal lobe
      resection and fourteen controls. During the task, abstract visual stimuli had to
      be associated, by trial and error, with a spatially oriented joystick motor
      response. Response and decision time were analyzed. Statistical analysis
      disclosed that the learning curve slopes of both RTR and LTR patients were
      significantly shallower compared to controls, LTR patients needed a number of
      test trials significantly increased compared to RTR patients and controls, the
      average probability of success in the test trials was significantly lower in LTR
      patients compared to RTR patients and controls, and RTR patients' decision times
      were significantly longer than LTR patients and controls. The results suggest
      that RTR patients, using the preserved verbalization strategy, achieved higher
      learning scores than LTR patients, which were forced to use a visuo-spatial
      representation of the stimuli-response association. Accordingly, RTR patients
      were significantly slower, compared to LTR patients and controls, indicating that
      processes involving recall were partially impaired, and non-canonical networks
      for executing a non-verbal task could be in action.

PMID- 22366055
TI  - Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but
      paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice.
AB  - Niemann Pick type C (NPC) disease is a progressive neurodegenerative disease
      caused by mutations in NPC1 or NPC2, the gene products of which are involved in
      cholesterol transport in late endosomes. NPC is characterized by an accumulation
      of cholesterol, sphingomyelin and glycosphingolipids in the visceral organs,
      primarily the liver and spleen. In the brain, there is a redistribution of
      unesterified cholesterol and a concomitant accumulation of glycosphingolipids. It
      has been suggested that reducing the aberrant lysosomal storage of
      glycosphingolipids in the brain by a substrate reduction therapy (SRT) approach
      may prove beneficial. Inhibiting glucosylceramide synthase (GCS) using the
      iminosugar-based inhibitor miglustat (NB-DNJ) has been reported to increase the
      survival of NPC mice. Here, we tested the effects of Genz-529468, a more potent
      iminosugar-based inhibitor of GCS, in the NPC mouse. Oral administration of Genz
      529468 or NB-DNJ to NPC mice improved their motor function, reduced CNS
      inflammation, and increased their longevity. However, Genz-529468 offered a wider
      therapeutic window and better therapeutic index than NB-DNJ. Analysis of the
      glycolipids in the CNS of the iminosugar-treated NPC mouse revealed that the
      glucosylceramide (GL1) but not the ganglioside levels were highly elevated. This
      increase in GL1 was likely caused by the off-target inhibition of the murine non
      lysosomal glucosylceramidase, Gba2. Hence, the basis for the observed effects of
      these inhibitors in NPC mice might be related to their inhibition of Gba2 or
      another unintended target rather than a result of substrate reduction.

PMID- 22366056
TI  - Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid
      differentiated HL-60 cells, granulocytes, and monocytes.
AB  - The sex hormones are known to affect innate immunity in humans. In this study we
      evaluated the immunomodulatory effects of testosterone in a model system
      comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed
      the results in human granulocytes and monocytes. Results showed that testosterone
      at pharmacological doses reduced the production of interleukin-8 and reactive
      oxygen species from differentiated HL-60 cells in a concentration dependent
      manner without affecting phagocytosis. The cells were stimulated with zymosan,
      lipopolysaccharide, or Bacillus subtilis. At the highest concentration of
      testosterone (120 MUM), interleukin-8 secretion was reduced 42-80%, and
      production of reactive oxygen species was reduced 32-46%. Flutamide, an
      antagonist of the classical intracellular androgen receptor, was unable to
      antagonize the immunosuppressive effect of testosterone. We further demonstrated
      that the suppressive effect of testosterone has a short onset time. Our results
      suggest that testosterone affects the fast operating membrane bound androgen
      receptor or a rapid acting enzyme system. Testosterone, at pharmacological doses,
      was also shown to suppress generation of reactive oxygen species and interleukin
      8 in human granulocytes and monocytes, respectively, to a similar extent as
      observed in differentiated HL-60 cells.

PMID- 22366057
TI  - Allele-specific gene expression and epigenetic modifications and their
      application to understanding inheritance and cancer.
AB  - Epigenetic information is characterized by its plasticity during development and
      differentiation as well as its stable transmission during mitotic cell divisions
      in somatic tissues. This duality contrasts to genetic information, which is
      essentially static and identical in every cell in an organism with only a few
      exceptions such as immunoglobulin genes in lymphocytes. Epigenetics is
      traditionally perceived as a means to regulate gene expression without a change
      in DNA sequence. This, however, does not exclude a potential role for genetic
      variations in providing differential backgrounds on which epigenetic modulations
      and their regulatory consequences are achieved. An effective approach to
      investigating the interplay between genetic variations and epigenetic variations
      is through allele-specific analysis of epigenetics and gene expression. Such
      studies have generated many new insights into functions of genetic variations,
      mechanisms of gene expression regulation, and the role of mutations and
      epigenetic alterations in human cancer. This article is part of a Special Issue
      entitled: Chromatin in time and space.

PMID- 22366058
TI  - Characterization of starch Pickering emulsions for potential applications in
      topical formulations.
AB  - The aim of this work has been to characterize starch based Pickering emulsions as
      a first step to evaluate their possible use as vehicles for topical drug
      delivery. A minor phase study of emulsions with high oil content has been
      performed. Emulsion stability against coalescence over eight weeks and after mild
      centrifugation treatment has been studied. The particle size, rheological
      properties and in vitro skin penetration of emulsions containing three different
      oils (Miglyol, paraffin and sheanut oil) was investigated. It was shown that it
      is possible to produce oil in water starched stabilised Pickering emulsions with
      oil content as high as 56%. Furthermore, this emulsions show good stability
      during storage over eight weeks and towards mild centrifugation. The particle
      size of the systems are only dependent on the ratio between oil and starch and
      for liquid oils the type of oil do not affect the particle size. The type of oil
      also affects the cosmetic and rheological properties of the creams but did not
      affect the transdermal diffusion in in vitro tests. However, it seems as if the
      Pickering emulsions affected the transport over the skin, as the flux was twice
      that of what has been previously reported for solutions.

PMID- 22366059
TI  - Neuronal and intracellular signaling pathways mediating GLP-1 energy balance and
      glycemic effects.
AB  - The glucagon-like peptide-1 (GLP-1) system is physiologically involved in the
      control of energy balance and blood glucose homeostasis. Thus, GLP-1-based
      pharmaceuticals are emerging as a potent treatment for not only type II diabetes
      mellitus (T2DM), but potentially for obesity as well. Despite the plethora of
      investigations over the last two decades examining the physiological, endocrine,
      and behavioral responses mediated by the GLP-1 receptor (GLP-1R), the field is
      only recently embracing the perspective that GLP-1-mediated control of food
      intake and glycemia involves action on GLP-1R that are distributed throughout the
      periphery (e.g. pancreatic beta-cells, vagus nerve), as well as action on many
      GLP-1R-expressing nuclei within the central nervous system (CNS). This review
      highlights peripheral, as well as central GLP-1R populations that mediate GLP-1's
      food intake inhibitory and glycemic effects. In addition, focus is devoted to
      recent studies that examine the GLP-1R-mediated intracellular signaling pathways
      that are required for GLP-1's glycemic and feeding responses.

PMID- 22366060
TI  - Focal adhesion kinase negatively regulates neuronal insulin resistance.
AB  - Focal adhesion kinase (FAK), a non-receptor protein kinase, is known to be a
      phosphatidyl inositol 3-kinase (PI3K) pathway activator and thus widely
      implicated in regulation of cell survival and cancer. In recent years FAK has
      also been strongly implicated as a crucial regulator of insulin resistance in
      peripheral tissues like skeletal muscle and liver, where decrease in its
      expression/activity has been shown to lead to insulin resistance. However, in the
      present study we report an altogether different role of FAK in regulation of
      insulin/PI3K signaling in neurons, the post-mitotic cells. An aberrant increase
      in FAK tyrosine phosphorylation was observed in insulin resistant Neuro-2a (N2A)
      cells. Downregulation of FAK expression utilizing RNAi mediated gene silencing in
      insulin resistant N2A cells completely ameliorated the impaired insulin/PI3K
      signaling and glucose uptake. FAK silencing in primary cortical neurons also
      showed marked enhancement in glucose uptake. The results thus suggest that in
      neurons FAK acts as a negative regulator of insulin/PI3K signaling.
      Interestingly, the available literature also demonstrates cell-type specific
      functions of FAK in neurons. FAK that is well known for its cell survival effects
      has been shown to be involved in neurodegeneration. Along with these previous
      reports, present findings highlight a novel and critical role of FAK in neurons.
      Moreover, as this implicates differential regulation of insulin/PI3K pathway by
      FAK in peripheral tissues and neuronal cells, it strongly suggests precaution
      while considering FAK modulators as possible therapeutics.

PMID- 22366062
TI  - Evolutionary analyses of gap junction protein families.
AB  - Gap junctions are intercellular channels that link the cytoplasm of neighboring
      cells in animals, enabling straight passage of ions and small molecules. Two
      different protein families, pannexins and connexins, form these channels.
      Pannexins are present in all eumetazoans but echinoderms (and are termed innexins
      in non-chordates) whereas connexins are exclusive of chordates. Despite little
      sequence similarity, both types of proteins assemble into a common secondary
      structure with four hydrophobic transmembrane domains linked by one cytoplasmic
      and two extracellular loops. Although all pannexins and connexins are packed into
      hexamers forming single channels, only non-chordate pannexins (innexins) and
      connexins form gap junctions. Here, we revisit and review evolutionary features
      of pannexin and connexin protein families. For that, we retrieved members of both
      families from several complete genome projects, and searched for conserved
      positions in the independent alignments of pannexin and connexin protein
      families. In addition, the degree of evolutionary conservation was mapped onto
      the 3D structure of a connexon (i.e. the assembly of six connexins). Finally, we
      reconstructed independent phylogenies of pannexins and connexins using
      probabilistic methods of inference. Non-chordate (Drosophila and Caenorhabditis)
      pannexins (i.e. innexins) were recovered as sister group of chordate pannexins,
      which included Ciona paralogs and vertebrate pannexins (pannexin-1 and pannexin-3
      were recovered as sister groups to the exclusion of pannexin-2). In the
      reconstructed phylogeny of connexins, subfamilies alpha and beta were recovered
      as sister groups to the exclusion of subfamily gamma, whereas delta and (the
      newly identified) zeta subfamilies were recovered at the base of the tree. A
      sixth highly divergent subfamily (epsilon) was not included in the phylogenetic
      analyses. Several groups of paralogy were identified within each subfamily. This
      article is part of a Special Issue entitled: The Communicating junctions, roles
      and dysfunctions.

PMID- 22366061
TI  - Peroxisomal acyl-CoA synthetases.
AB  - Peroxisomes carry out many essential lipid metabolic functions. Nearly all of
      these functions require that an acyl group-either a fatty acid or the acyl side
      chain of a steroid derivative-be thioesterified to coenzyme A (CoA) for
      subsequent reactions to proceed. This thioesterification, or "activation",
      reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase family, is
      thus central to cellular lipid metabolism. However, despite our rather thorough
      understanding of peroxisomal metabolic pathways, surprisingly little is known
      about the specific peroxisomal acyl-CoA synthetases that participate in these
      pathways. Of the 26 acyl-CoA synthetases encoded by the human and mouse genomes,
      only a few have been reported to be peroxisomal, including ACSL4, SLC27A2, and
      SLC27A4. In this review, we briefly describe the primary peroxisomal lipid
      metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the
      evidence for presence and functions of acyl-CoA synthetases in peroxisomes, much
      of which was obtained before the existence of multiple acyl-CoA synthetase
      isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific acyl
      CoA synthetase isoforms in lipid metabolism.

PMID- 22366063
TI  - Administration of recombinant Reishi immunomodulatory protein (rLZ-8) diet
      enhances innate immune responses and elicits protection against nervous necrosis
      virus in grouper Epinephelus coioides.
AB  - Nervous necrosis virus (NNV) infection during larvae and juvenile stage in
      grouper (Epinephelus coioides) has caused severe economic losses in the
      aquaculture industry in Asia. The aims of this study were to evaluate the
      influence of recombinant Reishi protein, rLZ-8, on the innate immune responses
      and the viral resisting ability in fish. Groupers were fed with rLZ-8
      supplemented diet (1.25-37.5 mg (rLZ-8)/kg(diet)), and the cytokine gene
      expression, innate immune responses, and survival rate after NNV challenge were
      examined. The fish fed with rLZ-8 diet showed 6- to 11-fold upregulated TNF-alpha
      and IL-1beta gene expression, along with significant increased respiratory burst
      and phagocytic activity. Moreover, feeding the fish with 37.5 mg/kg rLZ-8 diet
      elicited significant improvement in post viral challenge survival rate (85.7%).
      These discoveries indicated that rLZ-8 could be utilized as an ant-pathogen
      immunostimulant, and provided a new candidate to fight against NNV infection in
      fish.

PMID- 22366064
TI  - RNA-seq analysis of mucosal immune responses reveals signatures of intestinal
      barrier disruption and pathogen entry following Edwardsiella ictaluri infection
      in channel catfish, Ictalurus punctatus.
AB  - The mucosal surfaces of fish (gill, skin, gastrointestinal tract) are important
      sites of bacterial exposure and host defense mechanisms. In mammalian systems,
      the intestinal epithelium is well characterized as both a selectively permeable
      barrier regulated by junctional proteins and as a primary site of infection for a
      number of enteric pathogens including viruses, bacteria, and parasites. The
      causative bacterium of enteric septicemia of catfish, Edwardsiella ictaluri, is
      believed to gain entry through the intestinal epithelium, with previous research
      using a rat intestinal epithelial cell line (IEC-6) indicating actin
      polymerization and receptor-mediated endocytosis as potential mechanisms of
      uptake. Here, we utilized high-throughput RNA-seq to characterize the role of the
      intestinal epithelial barrier following E. ictaluri challenge. A total of 197.6
      million reads were obtained and assembled into 176,481 contigs with an average
      length of 893.7 bp and N50 of 1676 bp. The assembled contigs contained 14,457
      known unigenes, including 2719 genes not previously identified in other catfish
      transcriptome studies. Comparison of digital gene expression between challenged
      and control samples revealed 1633 differentially expressed genes at 3 h, 24 h,
      and 3 day following exposure. Gene pathway analysis of the differentially
      expressed gene set indicated the centrality of actin cytoskeletal
      polymerization/remodelling and junctional regulation in pathogen entry and
      subsequent inflammatory responses. The expression patterns of fifteen
      differentially expressed genes related to intestinal epithelial barrier
      dysfunction were validated by quantitative real-time RT-PCR (average correlation
      coeff. 0.92, p < 0.001). Our results set a foundation for future studies
      comparing mechanisms of pathogen entry and mucosal immunity across several
      important catfish pathogens including E. ictaluri, Edwardsiellatarda,
      Flavobacterium columnare, and virulent atypical Aeromonas hydrophila.
      Understanding of molecular mechanisms of pathogen entry during infection will
      provide insight into strategies for selection of resistant catfish brood stocks
      against various diseases.

PMID- 22366065
TI  - Molecular characterization, expression, and functional analysis of two
      thioredoxins in the black rockfish (Sebastes schlegelii).
AB  - Thioredoxins (TRxs) are a family of small evolutionarily conserved proteins that
      are essential for the maintenance of cellular homeostasis. Two TRx homologue
      cDNAs were isolated from a black rockfish concanavalin A (Con A)/phorbol
      myristate acetate (PMA)-stimulated leucocyte cDNA library and named BrTPx1-1 and
      BrTPx1-2. As compared with other known TRx peptide sequences, the most conserved
      regions of both BrTRx1-1 and BrTRx1-2 peptides were found to be the redox-active
      site Trp-Cys-X-X-Cys (WCXXC). The TRx present in most species is a TRx1-2 protein
      with a Cys-Pro-Gly-Cys (CPGC) active site. However, in the larger 13 kDa BrTRx1-1
      protein, a Cys-Pro-Pro-Cys (CPPC) active site was identified. Here, we report the
      identification of a new member of the TRx protein family from the teleost black
      rockfish, which defines a new subclass of 13-kDa TRx1-1 proteins. Phylogenetic
      analysis indicated that both BrTRx1-1 and BrTRx1-2 were grouped with other
      vertebrate TRx1 peptides. BrTRx1-1 expression was strongly induced in peripheral
      blood leucocytes (PBLs) 12-24 h following Con A/PMA stimulation, with peak
      expression at 24 h post-stimulation. BrTRx1-2 was induced in PBLs after
      stimulation with lipopolysaccharide (LPS), Con A/PMA, or poly I:C at 24 h. The
      BrTRx1-1 gene was predominantly expressed in the liver and gills, while BrTRx1-2
      was expressed in PBLs and gills. After treatment with a high concentration (10
      MUg/mL) of rBrTRx1-1 or rBrTRx1-2, kidney leucocytes exhibited increased cell
      proliferation and viability under oxidative stress.

PMID- 22366066
TI  - Acute and sublethal effects in an Indian major carp Cirrhinus mrigala exposed to
      silver nitrate: Gill Na+/K+-ATPase, plasma electrolytes and biochemical
      alterations.
AB  - Due to prolonged use of silver in many applications, it enters into the
      freshwater and affects the aquatic organisms. Fingerlings of Cirrhinus mrigala
      were exposed to acute and sublethal concentrations of silver nitrate and the
      alterations of gill Na(+)/K(+)-ATPase, plasma electrolytes and biochemical
      parameters were assessed. The median lethal concentration of silver nitrate to
      the fish C. mrigala for 96 h was found to be 0.107 mg/l (with 95% confidence
      limits). 1/10th of LC 50 96 h value (0.0107 mg/l) was selected for sublethal
      study. During acute treatment branchial Na(+)/K(+)-ATPase activity was inhibited
      approximately 44.34% after 96 h of exposure. In sublethal treatment, silver
      nitrate could not produce a significant change in the activity of the enzyme at
      the end of 7th day. However, after 14th day, significant (p < 0.05) decrease was
      noted showing 22.52%-49.11% in rest of the study period. Silver intoxication
      resulted hyponatremia, hypokalemia, hypochloremia, and hypoproteinemia in both
      the treatments. Despite the decrease in these parameters, plasma glucose level
      was found to be increased in both the treatments to endure the silver toxicity.
      We suggest that the alterations in branchial Na(+)/K(+)-ATPase activity, plasma
      electrolytes, and biochemical parameters of fish may be useful in environmental
      biomonitoring and to assess the health of fish in freshwater habitat contaminated
      with silver.

PMID- 22366067
TI  - pH sensitive silica nanotubes as rationally designed vehicles for NSAIDs
      delivery.
AB  - A novel pH-sensitive drug delivery system based on functionalized silica
      nanotubes was developed for the incorporation of non-steroidal anti-inflammatory
      drugs (NSAIDs), aimed at a tailored drug release in acidic conditions
      characteristic of inflamed tissues. Silica nanotubes (SNTs) were synthesized by a
      nanoporous alumina template assisted sol-gel method. Inner surfaces were
      physically and chemically modified to improve both the functionalization and
      subsequent incorporation of the drug. Fourier transform infrared spectroscopy
      (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS)
      and transmission electron microscopy (TEM) were used to characterize the designed
      nanocarriers and their functionalization. To achieve the highest degree of
      functionalization, three types of aminosilanes were tested and calcination
      conditions were optimized. APTES was shown to be the most effective aminosilane
      regarding the functionalization of the SNTs' inner surface and an adequate
      calcination temperature (220 degrees C) was found to attain mechanical stability
      without compromising functionalization efficiency. Finally, the incorporation of
      naproxen into the nanotubes was accessed by fluorescence measurements and drug
      release studies were performed, revealing that the electrostatic linkage ensures
      effective release of the drug in the acidic pH typical of inflamed cells, while
      maintaining the SNT-drug conjugates stable at the typical bloodstream pH.

PMID- 22366068
TI  - Determination of main components in the extracellular polymeric substances
      extracted from activated sludge using a spectral probing method.
AB  - In this study, a spectral probing method was applied to determine the content of
      the main components, i.e., proteins, polysaccharides and humic substances, in the
      extracellular polymeric substances (EPS) extracted from activated sludge. The
      measurement results were consistent with those obtained from the conventional
      methods, such as the anthrone for polysaccharide determination, the modified
      Lowry method for protein and humic substance determination. The recoveries for
      the determination of proteins, humic substances and polysaccharides in the EPS
      extracted from six sludge samples using standard additional method were between
      92.4 and 108.9%, 84.8 and 108.9%, 75.1 and 117.2%, respectively. These results
      indicate that the propose method has a good accuracy and precision, and can be
      used as an effective approach to determine the main components in sludge EPS.

PMID- 22366069
TI  - Micelle-catalyzed reaction between ninhydrin and nickel dipeptide complex [Ni(II)
      Gly-Tyr]+.
AB  - The interaction of nickel dipeptide complex [Ni(II)-Gly-Tyr](+) with ninhydrin
      has been investigated in the absence and presence of cationic
      cetyltrimethylammonium bromide (CTAB) and gemini (16-s-16, s=4, 5, 6) surfactants
      spectrophotometrically at 80 degrees C and pH 5.0. The product formed was the
      same and the reaction followed first- and fractional-order kinetics with respect
      to [Ni(II)-Gly-Tyr](+) and [ninhydrin], respectively, in both aqueous as well as
      micellar media. In the presence of CTAB, rate increased and reached up to a
      maximum, then decreased. Also, whereas typical rate constant (k(Psi)) increase
      and leveling-off regions, just like CTAB, were observed with geminis, the latter
      produced a third region of increasing k(Psi) at higher concentrations. This
      unusual third-region effect of the gemini micelles is assigned to changes in
      their micellar morphologies. The micellar catalysis is explained in terms of
      pseudo-phase model. The binding constants and the values of activation parameters
      such as activation energy (E(a)), enthalpy of activation (DeltaH(#)) and entropy
      of activation (DeltaS(#)) have been evaluated.

PMID- 22366071
TI  - Neuropsychological functions in bipolar disorders I and II with and without
      comorbid alcohol dependence.
AB  - OBJECTIVE: Bipolar disorder (BP) is a mental disorder most likely to co-occur
      with substance dependence and abuse, especially alcohol dependence (ALD). Whether
      the effect of comorbid alcoholism is different between the BP-I and BP-II
      subtypes remains unclear. We aimed to identify the neuropsychological performance
      of BP patients with and without comorbid ALD in partial remission from depression
      or mania, and compare it with that of healthy controls (HCs). METHODS: We
      recruited 29 HCs and 94 BP patients, whom we categorized into four groups: (1) BP
      I without a history of alcohol abuse or dependence (BP-I(-ALD); n=22), (2) BP-II
      without a history of alcohol abuse and dependence (BP-II(-ALD); n=38), (3) BP-I
      with comorbid ALD (BP-I(+ALD); n=16), and (4) BP-II with comorbid ALD (BP
      II(+ALD); n=18). Only males were recruited in this study. RESULTS: When patients
      comorbid with ALD were not excluded, there were no significant differences on
      neuropsychological tests between the BP-I and BP-II groups. However, when
      patients with comorbid ALD were excluded, there were significant differences
      between the two BP(-ALD) groups. The BP-I(-ALD) group had lower scores on memory
      subtests (p<=0.01) than the HC and BP-II(-ALD) groups, but the BP-II(-ALD) and HC
      groups had similar scores. CONCLUSION: We found it important to exclude ALD
      comorbidity when evaluating neuropsychological functions due to our finding that
      ALD affected the cognitive performance in BP-I more severely than in the BP-II
      group. ALD not only impairs neuropsychological function, but also worsen the
      clinical course and leads to a more pernicious status and negative cycle.

PMID- 22366070
TI  - Enhanced stability of polyacrylate-coated magnetite nanoparticles in biorelevant
      media.
AB  - Magnetite nanoparticles (MNPs) were prepared by alkaline hydrolysis of Fe(II) and
      Fe(III) chlorides. Adsorption of polyacrylic acid (PAA) on MNPs was measured at
      pH=6.5+/-0.3 and I=0.01 M (NaCl) to find the optimal PAA amount for MNP
      stabilization under physiological conditions. We detected an H-bond formation
      between magnetite surface groups and PAA by ATR-FTIR measurements, but bonds of
      metal ion-carboxylate complexes, generally cited in literature, were not
      identified at the given pH and ionic strength. The dependence of the
      electrokinetic potential and the aggregation state on the amount of added PAA at
      various pHs was measured by electrophoretic mobility and dynamic light-scattering
      methods. The electrokinetic potential of the naked MNPs was low at near
      physiological pH, but PAA adsorption overcharged the particles. Highly negatively
      charged, well-stabilized carboxylated MNPs formed via adsorption of PAA in an
      amount of approximately ten times of that necessary to compensate the original
      positive charge of the magnetite. Coagulation kinetics experiments revealed
      gradual enhancement of salt tolerance at physiological pH from ~0.001 M at no
      added PAA up to ~0.5 M at 1.12 mmol/g PAA. The PAA-coated MNPs exert no
      substantial effect on the proliferation of malignant (HeLa) or non-cancerous
      fibroblast cells (MRC-5) as determined by means of MTT assays.

PMID- 22366072
TI  - Alteration in expression of estrogen receptor isoforms alpha and beta, and
      aromatase in the testis and its relation with changes in nitric oxide during
      aging in mice.
AB  - The aim of present study was to investigate the changes in the testicular
      expression of aromatase, ER alpha, ER beta and iNOS protein and correlate these
      with serum testosterone and nitric oxide levels, to elucidate the role of
      estrogen and nitric oxide in the testis during aging. This study showed
      localization of aromatase and ER alpha mainly in the Leydig cell and showed close
      correlation of testicular aromatase level with circulating testosterone level
      suggesting that estrogen may be modulating testicular steroidogenesis.
      Localization ER alpha mainly in the mitotically active germ cell suggest possible
      role of estrogen in germ cell proliferation. This study showed basal level of
      nitric oxide during reproductively active period, whereas increased serum nitric
      oxide coincides with decreased testicular activity in old age. This study showed
      inverse correlation between aromatase and NO level. Treatment with either SNP or
      L-NAME on testicular steroidogenic factor (3-beta HSD/ StAR) or germ cell
      survival factor (Bcl2) showed that increased NO causes decreased steroidogenesis
      and increased germ cell apoptosis. In conclusion this study suggest that estrogen
      modulate steroidogenesis and germ cell survival in reproductively active period
      whereas in old age decreased estrogen concentration causes increased nitric oxide
      which in turn decreases testicular steroidogenesis and germ cell apoptosis.

PMID- 22366073
TI  - Atropodiastereoselectivity in solid state BINOL synthesis: leads from the
      estradiol platform.
AB  - A novel functionalized steroidal BINOL scaffold is produced via a remarkable
      sequence of dehydrogenation, chlorination and atroposelective phenolic coupling
      steps. Its formation is straightforwardly obtained in a one-step synthesis under
      solid state conditions and in the absence of chiral additives.

PMID- 22366074
TI  - 27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of
      26-hydroxylated sterols.
AB  - Significant ambiguity exists in the scientific community with regard to the
      nomenclature of 26-hydroxylated oxysterols. Oxysterols constitute an important
      class of compounds that have biological roles in the regulation of cholesterol
      synthesis and as endogenous selective estrogen receptor modulators (SERMs). The
      ambiguity is attributable to deviations from clearly stated IUPAC rules and is
      likely to increase as more biologically active oxysterols are identified. This
      review provides a uniform approach to the naming of 26-hydroxylated sterols for
      those of current interest and for those on the horizon such as oxysterols of
      lanosterol that retain the unsaturation at C-24 and C-25 such as (E)-26
      hydroxylanosterol. Using this molecule as a starting point, this review hopes to
      establish a common language to keep all investigators on the same page.

PMID- 22366075
TI  - Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal
      derivatives possessing potent diversified pharmacological properties.
AB  - As a part of our investigations into the structural-activity relationship studies
      of a novel class of medicinally active 16-substituted steroids, several new 16
      imidazolyl substituted steroidal derivatives have been synthesized and
      pharmacologically evaluated in the current study. The new steroidal analogues 5,
      6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell
      lines derived from nine cancers types. The imidazolyl substituted steroidal
      derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful
      inhibitors of aromatase with IC50=0.18 MUM and IC50=0.168 MUM, respectively,
      approximately 1.2 and 1.4 times more potent in comparison to standard drug
      exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal
      muscle relaxant properties. An affinity constant of 0.007 MUM was observed for
      compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very
      high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in
      comparison to standard drug galanthamine (K(i)=2.9 MUM).

PMID- 22366076
TI  - Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral
      outcomes in the rat.
AB  - Previous work has indicated an association between seizures early in life and
      increased risk of psychiatric disorders, including schizophrenia. However,
      because early-life seizures are commonly treated with antiepileptic drugs (AEDs)
      such as phenobarbital, the possibility that drug treatment may affect later-life
      psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis
      that phenobarbital exposure in the neonatal rat increases the risk of
      schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we
      examined the effects of a single acute neonatal exposure to phenobarbital on
      adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion
      model of schizophrenia. We compared these outcomes to those in rats a) without
      nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for
      behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition,
      elevated plus-maze, and novel object recognition task. We found that neonatal
      phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt
      sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent
      equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced
      the locomotor response to amphetamine in adult animals with and without nVH
      lesions. Our findings suggest that neonatal exposure to phenobarbital can
      predispose to schizophrenia-like behavioral abnormalities. Our findings
      underscore the importance of examining AED exposure early in life as a potential
      risk factor for later-life neuropsychiatric abnormalities in clinical
      populations.

PMID- 22366078
TI  - Influences of disc degeneration and bone mineral density on the structural
      properties of lumbar end plates.
AB  - BACKGROUND CONTEXT: Implants subsidence is a frequent complication of interbody
      fusion, which can result in pain, deformity, nerve damage, and even failure of
      surgery. The end plates as the interface between implants and the vertebral
      bodies play a very important role in sharing the compression on the vertebral
      bodies. The information on the structural property distribution of the end plate
      and its relationship with bone mineral density (BMD) and disc degeneration will
      be of great significance for the reduction in implants subsidence and improvement
      in related operative procedures to increase the success rate of interbody fusion.
      PURPOSE: To investigate the structural property distribution of the lumbar end
      plate; the effects of disc degeneration on the biomechanical properties of the
      lumbar end plate; and the relationship between the biomechanical properties of
      the lumbar end plate and BMD. STUDY DESIGN: A biomechanical study was conducted
      in human cadaveric lumbar spine models. METHODS: Indentation tests were performed
      at 24 standardized test sites in 120 bony end plates of intact human vertebrae
      (L1-L5) using a 1.5-mm-diameter, hemispherical indenter at a speed of 0.2mm/s.
      The failure load at each test site was determined using the load-displacement
      curve. Disc condition was evaluated using a four-point grading scale and bone
      density was measured using the lateral dual-energy radiograph absorptiometry
      scans. All end plates were divided into different disc degeneration groups based
      on the states of the adjacent degenerative discs and BMD groups according to BMD
      values of the corresponding vertebral bodies. The experimental results were
      statistically analyzed using the SPSS 15.0 with the disc degeneration and BMD
      being considered as independent factor, and the failure loads of the superior and
      inferior end plates were also compared. RESULTS: The peripheral regions of lumbar
      end plates were stronger than the central regions (p<.05), with the
      posterolateral sites in front of vertebral pedicles being the strongest regions.
      The inferior lumbar end plates were found to be stronger than the superior lumbar
      end plates (p<.05). The disc degeneration was negatively correlated with the
      failure loads of the lumbar end plates (r(s)=-0.563; p<.01). With increasing disc
      degeneration, the decreases of failure loads were nonuniform across the lumbar
      end plate, and the central region became weak with little strength change on the
      end plate periphery. The BMD was positively correlated with the failure loads of
      the lumbar end plates (r(s)=0.812; p<.01). The failure loads decreased uniformly
      across the end plate surfaces as the BMD dropped, and the BMD decrease did not
      change the structural property distributions of lumbar end plates. CONCLUSIONS:
      Preoperative evaluation of the states of intervertebral discs and BMD of patients
      is necessary for predicting risks of implants subsidence after interbody fusion.
      For patients with or without disc degeneration or osteoporosis, the implants
      should be placed at the peripheral regions, especially the posterolateral sites,
      to acquire higher mechanical strength to reduce subsidence as much as possible.

PMID- 22366077
TI  - Mechanism of H2 histamine receptor dependent modulation of body temperature and
      neuronal activity in the medial preoptic nucleus.
AB  - Histamine is involved in the central control of arousal, circadian rhythms and
      metabolism. The preoptic area, a region that contains thermoregulatory neurons is
      the main locus of histamine modulation of body temperature. Here we report that
      in mice, histamine activates H(2) subtype receptors in the medial preoptic
      nucleus (MPON) and induces hyperthermia. We also found that a population of
      glutamatergic MPON neurons express H(2) receptors and are excited by histamine or
      H(2) specific agonists. The agonists decreased the input resistance of the neuron
      and increased the depolarizing "sag" observed during hyperpolarizing current
      injections. Furthermore, at -60 mV holding potential, activation of H(2)
      receptors induced an inward current that was blocked by ZD7288, a specific
      blocker of the hyperpolarization activated cationic current (I(h)). Indeed,
      activation of H(2) receptors resulted in increased I(h) amplitude in response to
      hyperpolarizing voltage steps and a depolarizing shift in its voltage-dependent
      activation. The neurons excited by H(2) specific agonism expressed the HCN1 and
      HCN2 channel subunits. Our data indicate that at the level of the MPON histamine
      influences thermoregulation by increasing the firing rate of glutamatergic
      neurons that express H(2) receptors.

PMID- 22366079
TI  - Orientation of noisy texture affects saccade direction during free viewing.
AB  - We redirect our eye approximately three times per second to bring a new part of
      our environment on to our fovea (Findlay & Gilchrist, 2003). How a scanning path
      is planned is still an unsolved matter. Most research to date has focused on the
      question of target selection: how is the next fixation location, or saccade
      target, selected. Here we investigated the direction of spontaneous saccades,
      rather than fixation locations per se. We measured eye movements, while observers
      were freely viewing noisy textures: oriented gabors embedded in either pink (1/f)
      noise or pixel noise, of which they later had to report their orientation. Our
      results show that a significant percentage of the spontaneous saccades were
      directed along the orientation of the stimulus. These results suggest that
      observers may have used an underlying eye movement strategy involving the search
      for contour endings. 

PMID- 22366080
TI  - Enhancing reproducibility of fMRI statistical maps using generalized canonical
      correlation analysis in NPAIRS framework.
AB  - Common fMRI data processing techniques usually minimize a temporal cost function
      or fit a temporal model to extract an activity map. Here, we focus on extracting
      a highly, spatially reproducible statistical parametric map (SPM) from fMRI data
      using a cost function that does not depend on a model of the subjects' temporal
      response. Based on a generalized version of canonical correlation analysis
      (gCCA), we propose a method to extract a highly reproducible map by maximizing
      the sum of pair-wise correlations between some maps. In a group analysis, each
      map is calculated from a linear combination of fMRI scans of a subset of subjects
      under study. The proposed method is applied to BOLD fMRI datasets without any
      spatial smoothing from 10 subjects performing a simple reaction time (RT) task.
      Using the NPAIRS split-half resampling framework with a reproducibility measure
      based on SPM correlations, we compare the proposed approach with canonical
      variate analysis (CVA) and a simple general linear model (GLM). gCCA provides
      statistical parametric maps with higher reproducibility than CVA and GLM with
      correlation reproducibilities across independent split-half SPMs of 0.78, 0.46,
      and 0.41, respectively. Our results show that gCCA is an efficient approach for
      extracting the default mode network, assessing brain connectivity, and processing
      event-related and resting-state datasets in which the temporal BOLD signal varies
      from subject to subject.

PMID- 22366081
TI  - The continuing challenge of understanding and modeling hemodynamic variation in
      fMRI.
AB  - Interpretation of fMRI data depends on our ability to understand or model the
      shape of the hemodynamic response (HR) to a neural event. Although the HR has
      been studied almost since the beginning of fMRI, we are still far from having
      robust methods to account for the full range of known HR variation in typical
      fMRI analyses. This paper reviews how the authors and others contributed to our
      understanding of HR variation. We present an overview of studies that describe HR
      variation across voxels, healthy volunteers, populations, and dietary or
      pharmaceutical modulations. We also describe efforts to minimize the effects of
      HR variation in intrasubject, group, population, and connectivity analyses and
      the limits of these methods.

PMID- 22366082
TI  - Quantitative comparison of resting-state functional connectivity derived from
      fNIRS and fMRI: a simultaneous recording study.
AB  - The feasibility of functional near-infrared spectroscopy (fNIRS) to assess
      resting-state functional connectivity (RSFC) has already been demonstrated.
      However the validity of fNIRS-based RSFC has rarely been studied. In the present
      study, fNIRS and fMRI data were simultaneously acquired from 21 subjects during
      the resting state. After the spatial correspondence was established between the
      two imaging modalities by transforming the fMRI data into fNIRS measurements
      space, the index of Between-Modality-Similarity (BMS) of RSFC was evaluated
      across multiple spatial scales. First, the RSFC between the bilateral primary
      motor ROI was quite similar between fNIRS and fMRI for all the subjects (BMS(ROI)
      = 0.95 +/- 0.04 for HbO and BMS(ROI) = 0.86 +/- 0.13 for HbR). Second, group
      level sensorimotor RSFC maps (0.79 for HbO and 0.74 for HbR) showed higher
      between-modality similarity than individual-level RSFC maps (0.48 +/- 0.16 for
      HbO and 0.41 +/- 0.15 for HbR). Finally, for the first time, we combined fNIRS
      and graph theory to investigate topological properties of resting-state brain
      networks. The clustering coefficient (C(p)) and characteristic path length (L(p))
      which are the most important network topological parameters, both showed high
      between-modality similarities (BMS(Cp) = 0.90 +/- 0.03 for HbO and 0.90 +/- 0.06
      for HbR; BMS(Lp) = 0.92 +/- 0.04 for HbO and 0.91 +/- 0.05 for HbR). In summary,
      the converged results across all the spatial scales demonstrated that fNIRS is
      capable of providing comparable RSFC measures to fMRI, and thus provide direct
      evidence for the validity of the optical brain connectivity and the optical brain
      network approaches to functional brain integration during resting state.

PMID- 22366083
TI  - Socio-economic status and cardiovascular risk factors in rural and urban areas of
      Vellore, Tamilnadu, South India.
AB  - BACKGROUND: We examined associations between socio-economic status (SES)
      indicators and cardiovascular disease (CVD) risk factors among urban and rural
      South Indians. METHODS: Data from a population-based birth cohort of 2218 men and
      women aged 26-32 years from Vellore, Tamilnadu were used. SES indicators included
      a household possessions score, attained education and paternal education. CVD
      risk factors included obesity, hypertension, impaired glucose tolerance or
      diabetes, plasma total cholesterol to high density lipoprotein (HDL) ratio and
      triglyceride levels and consumption of tobacco and alcohol. Multiple logistic
      regression analysis was used to assess associations between SES indicators and
      risk factors. RESULTS: Most risk factors were positively associated with
      possessions score in urban and rural men and women, except for tobacco use, which
      was negatively associated. Trends were similar with the participants' own
      education and paternal education, though weaker and less consistent. In a
      concurrent analysis of all the three SES indicators, adjusted for gender and
      urban/rural residence, independent associations were observed only for the
      possessions score. Compared with those in the lowest fifth of the score,
      participants in the highest fifth had a higher risk of abdominal obesity [odds
      ratio (OR) =6.4, 95% CI 3.4-11.6], high total cholesterol to HDL ratio (OR=2.4,
      95% CI 1.6-3.5) and glucose intolerance (OR=2.8, 95% CI 1.9-4.1). Their tobacco
      use (OR=0.4, 95% CI 0.2-0.6) was lower. Except for hypertension and glucose
      intolerance, risk factors were higher in urban than rural participants
      independently of SES. CONCLUSION: In this young cohort of rural and urban south
      Indians, higher SES was associated with a more adverse CVD risk factor profile
      but lower tobacco use.

PMID- 22366084
TI  - A pre-test post-test study of a brief educational intervention demonstrates
      improved knowledge of potential acute myocardial infarction symptoms and
      appropriate responses in cardiac rehabilitation patients.
AB  - BACKGROUND: Patient delay in recognizing and responding to potential acute
      myocardial infarction (AMI) symptoms is an international issue. Cardiac
      rehabilitation provides an ideal opportunity to deliver an intervention. AIMS:
      This study examines an individual educational intervention on knowledge of heart
      attack warning signs and specific chest pain action plans for people with
      coronary heart disease. METHODS: Cardiac rehabilitation participants at five
      hospitals were assessed at program entry and tailored education was provided
      using the Heart Foundation of Australia's Heart Attack Warning Signs campaign
      educational tool. Participants (n=137) were reassessed at program conclusion (six
      to eight weeks). RESULTS: Study participants had a mean age of 64.48 years (SD
      12.22), were predominantly male (78%) and most commonly presented with a current
      referral diagnosis of a percutaneous coronary intervention (PCI) (80%) and/or AMI
      (60%). There were statistically significant improvements in the reporting of 11
      of the 14 warning signs of heart attack, with patients reporting 2.56 more
      warning signs on average at outcome (p<.0001). Patients reported more heart
      attack warning signs if they had completed high school education (beta=1.14) or
      had better knowledge before the intervention (beta=.57). There were statistically
      significant improvements in reporting of all appropriate actions in response to
      potential AMI symptoms, with patients reporting an average of 1.3 more actions at
      outcome (p<.001), with no change in the median time they would tolerate symptoms
      (p=.16). CONCLUSIONS: A brief education session using a single standardised tool
      and adapted to a patient assessment is effective in improving knowledge of
      potential AMI symptoms and appropriate responses in cardiac rehabilitation up to
      two months following.

PMID- 22366085
TI  - Coronary care units continue to be effective at improving patient outcomes.

PMID- 22366086
TI  - Trimethylation of histone H3K4 is associated with the induction of fructose
      inducible genes in rat jejunum.
AB  - We previously reported that fructose force-feeding rapidly induces jejunal Slc2a5
      gene expression in rats. In this study, we conducted microarray analyses using
      total RNA to identify genes upregulated in rat jejunum by fructose force-feeding.
      Rats were force-fed fructose, glucose or distilled water for 6h. Genes such as
      Slc2a5, Cdkn1c, Cabp2, Ranbp3, Vwce and Gcgr were induced by force-feeding with
      fructose compared with glucose or distilled water. Chromatin immunoprecipitation
      assays revealed that trimethylation of histone H3K4, and acetylation of histones
      H3 and H4, on the transcribed region of these fructose-inducible genes were
      enhanced by force-feeding of fructose, but not glucose or distilled water. These
      results suggest that the induction of genes in the rat jejunum by fructose force
      feeding is coordinately regulated by histone modifications, particularly
      trimethylation of histone H3K4.

PMID- 22366087
TI  - XIAP reverses various functional activities of FRNK in endothelial cells.
AB  - In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation,
      migration, adhesion, and shear-stimulated activation of MAPK. We recently found
      that FAK is recruited into focal adhesion (FA) sites through interactions with
      XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src
      kinase in response to shear stress. In this study, we examined which domain(s) of
      FAK is(are) important for various vascular functions such as FA recruiting, XIAP
      binding and shear stress-stimulated ERK activation. Through a series of
      experiments, we determined that the FRNK domain is recruited into FA sites and
      promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to
      reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition,
      we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and
      FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and
      shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed
      by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in
      vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

PMID- 22366088
TI  - Analysis of AGE modified proteins and RAGE expression in HER2/neu negative
      invasive ductal carcinoma.
AB  - Cancer is associated with increased glycolysis and carbonyl stress. In view of
      this, AGE modified proteins were identified from clinical breast cancer tissue
      using 2DE-immunoblot and mass-spectrometry. These proteins were identified to be
      serotransferrin, fibrinogen gamma chain, glycerol-3-phosphate dehydrogenase,
      lactate dehydrogenase, annexin II, prohibitin and peroxiredoxin 6, which have
      established role in cancer. Further, RAGE expression and its downstream signaling
      proteins NADPH oxidase and NF-kB were studied. Role of these AGE modified
      proteins and RAGE signaling in breast cancer is discussed.

PMID- 22366089
TI  - NHE-1 blockade reversed changes in calcium transient in myocardial slices from
      isoproterenol-induced hypertrophied rat left ventricle.
AB  - We previously reported that left ventricular (LV) slices from isoproterenol (ISO)
      induced hypertrophied rat hearts showed an increase of energy expenditure due to
      remodeling of Ca(2+) handling in excitation-contraction coupling, i.e.,
      suppressed SERCA2a activity and enhanced Na(+)/Ca(2+)exchanger-1 (NCX-1)
      activity. Na(+)/H(+) exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated
      to exert beneficial effects in the development of cardiac remodeling. We
      hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling
      of Ca(2+) handling in LV slices of ISO-induced hypertrophied rat hearts mediated
      by inhibiting NCX-1 activity. The significant shortening in duration of multi
      cellular Ca(2+) transient in ISO group was normalized in ISO+BIIB723 group. The
      significant increase in amplitude of multi-cellular Ca(2+) waves (CaW) generated
      at high [Ca(2+)](o) of LV slices in ISO group was also normalized in ISO+BIIB723
      group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We
      recently reported that ISO-induced down-regulation of a Ca(2+) handling protein,
      SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723
      normalized shortened multi-cellular Ca(2+) transient duration and increased CaW
      amplitude in LV slices mediated via normalization of SERCA2a activity.
      Furthermore, the results presented here suggest the multi-cellular Ca(2+)
      transient duration and CaW amplitude in LV slices might be better indices
      reflecting SERCA2a activity than SERCA2a protein expression level.

PMID- 22366090
TI  - Polyubiquitin recognition by AtSAP5, an A20-type zinc finger containing protein
      from Arabidopsis thaliana.
AB  - Stress associated proteins (SAPs) in plants contain A20-type zinc finger (A20_ZF)
      domains and are involved with abiotic stress response. A20-type zinc finger
      domains in animals reportedly recognize ubiquitin as a regulatory signal in cell.
      However, it remains unclear whether A20_ZF domains in plants perform similar
      roles. AtSAP5, a SAP from Arabidopsis thaliana, exhibits a unique sequence
      feature among 10 AtSAPs harboring A20_ZF domains. The highly conserved diaromatic
      patch is replaced by the dialipathic patch. Here we investigated whether AtSAP5
      recognizes ubiquitin and the roles of the dialipathic patch in ubiquitin binding
      in vitro. GST pulldown assay reveals that AtSAP5 binds polyubiquitin rather than
      monoubiquitin. AtSAP5 shows preferences for linear and K63-linked polyubiquitin
      chains to K48-linked one. The A20_ZF domain of AtSAP5 is sufficient for linkage
      specific polyubiquitin recognition. The dialipathic patch in AtSAP5 plays an
      important role in K48-linked polyubiquitin recognition. Taken together, our
      results suggest that AtSAP5 participates in polyubiquitin recognition in plants
      and that the dialipathic patch in AtSAP5 is critical in binding K48-linked
      polyubiquitn chains.

PMID- 22366091
TI  - Silibinin inhibits the toxic aggregation of human islet amyloid polypeptide.
AB  - In type 2 diabetes mellitus (T2DM), misfolded human islet amyloid polypeptide
      (hIAPP) forms amyloid deposits in pancreatic islets. These amyloid deposits
      contribute to the dysfunction of beta-cells and the loss of beta-cell mass in
      T2DM patients. Inhibition of hIAPP fibrillization has been regarded as a
      potential therapeutic approach for T2DM. Silibinin, a major active flavonoid
      extracted from herb milk thistle (Silybum marianum), has been used for centuries
      to treat diabetes in Asia and Europe with unclear mechanisms. In this study, we
      tested whether silibinin has any effect on the amyloidogenicity of hIAPP. Our
      results provide first evidence that silibinin inhibits hIAPP fibrillization via
      suppressing the toxic oligomerization of hIAPP and enhances the viability of
      pancreatic beta-cells, therefore silibinin may serve as a potential therapeutic
      agent for T2DM.

PMID- 22366092
TI  - Crystal structure of the secretory isozyme of mammalian carbonic anhydrases CA
      VI: implications for biological assembly and inhibitor development.
AB  - Zn(2+)-dependent carbonic anhydrases (CA) catalyse the reversible hydration of
      carbon dioxide to bicarbonate and participate in diverse physiological processes,
      hence having manifold therapeutic potentials. Among the 15 human CAs with wide
      ranging sub-cellular localisation and kinetic properties, CA VI is the only
      secretory isoform. The 1.9A crystal structure of the human CA VI catalytic domain
      reveals a prototypical mammalian CA fold, and a novel dimeric arrangement as
      compared to previously-reported CA structures. The active site cavity contains a
      cluster of non-conserved residues that may be involved in ligand binding and have
      significant implications for developing the next-generation of isoform-specific
      inhibitors.

PMID- 22366093
TI  - Ethnoveterinary remedies of diseases among milk yielding animals in Kathua, Jammu
      and Kashmir, India.
AB  - The triangle of relationship between human beings, animals and plants has existed
      for ages, and has given rise to intense-relationships and consequently rich
      traditions of ethnoveterinary knowledge throughout the world. The predominantly
      rural population and the strong agricultural base have provided unique situation
      for rich ethnoveterinary practices in the study area. AIM OF THE STUDY: The
      present study was conducted in the Kathua district of Jammu and Kashmir between
      2007 and 2009 to provide list of the important plants of the region for further
      phytochemical and pharmacological studies, and to prepare inventory of the
      ethnoveterinary practices for the future generations. MATERIAL AND METHODS:
      Direct interview of 78 informants was conducted and the information gathered was
      analyzed for two quantitative methods viz. informant consensus factor (ICF) and
      use-value (UV). The characteristics of ethnoveterinary plants and practices were
      also documented. RESULTS: A total of 72 plants were used to cure 33 common
      ailments of milk yielding animals of Kathua district. Fabaceae (7 species) was
      the most represented family, along with Poaceae (6 species). Leaves (27.2%) were
      the most frequently used plant parts, herbs (48.6%) the most frequently used life
      form and wild flora (58.3%) the most used source for the ethnoveterinary
      practices. The highest ICF was reported for urological disorders (0.95) and
      lowest for nutritional diseases (0.80). The values of ICF were generally on the
      higher side which shows that the informants share the knowledge about the ailment
      among themselves. The important ethnoveterinary plant species on the basis of use
      values were: Brassica campestris, Saccharun officinarum, Emblica officinalis,
      Trachyspermum ammi, Asparagus adscendens, Musa paradisica, Oryza sativa, Curcuma
      longa, Azadirachta indica, Tinospora cordifolia and Tamarindus indica.
      CONCLUSION: High diversity of ethnoveterinary plants were found to cure the
      common milk yielding animals of Kathua district. Further phytochemical and
      pharmacological studies are required to ascertain their chemical nature for the
      betterment of the locals and farmers, and commercial utilization of this
      knowledge.

PMID- 22366094
TI  - Phylogenetic reconstruction and shell evolution of the Diplommatinidae
      (Gastropoda: Caenogastropoda).
AB  - The fascinating and often unlikely shell shapes in the terrestrial micromollusc
      family Diplommatinidae (Gastropoda: Caenogastropoda) provide a particularly
      attractive set of multiple morphological traits to investigate evolutionary
      patterns of shape variation. Here, a molecular phylogenetic reconstruction, based
      on five genes and 2700 bp, was undertaken for this family, integrated with
      ancestral state reconstruction and phylogenetic PCA of discrete and quantitative
      traits, respectively. We found strong support for the Diplommatininae as a
      monophyletic group, separating the Cochlostomatidae into a separate family. Five
      main clades appear within the Diplommatininae, corresponding with both coiling
      direction and biogeographic patterns. A Belau clade (A) with highly diverse (but
      always sinistral) morphology comprised Hungerfordia, Palaina, and some
      Diplommatina. Arinia (dextral) and Opisthostoma (sinistroid) are sister groups in
      clade B. Clade C and D solely contain sinistral Diplommatina that are robust and
      little ornamented (clade C) or slender and sculptured (clade D). Clade E is
      dextral but biogeographically diverse with species from all sampled regions save
      the Caroline Islands. Adelopoma, Diplommatina, Palaina, and Hungerfordia require
      revision to allow taxonomy to reflect phylogeny, whereas Opisthostoma is clearly
      monophyletic. Ancestral state reconstruction suggests a sinistral origin for the
      Diplommatinidae, with three reversals to dextrality.

PMID- 22366095
TI  - Genes implicated in insulin resistance are down-regulated in primary
      aldosteronism patients.
AB  - Primary aldosteronism (PA) patients display an increased incidence of insulin
      resistance. Herein we demonstrate the decreased gene expression of lipid
      metabolism genes PCK1, PLIN, ADIPOQ and PPARG in the visceral adipose tissue
      (VAT) of PA patients compared to age-, sex- and BMI-matched controls. In VAT, the
      expression of PCK1, PLIN, ADIPOQ and PPARG was inversely correlated with
      aldosterone levels; furthermore, PLIN and ADIPOQ gene expression was correlated
      with potassium levels. Therefore, raised aldosterone and low potassium may
      contribute to the reduced expression of these genes in PA patients. Finally,
      incubation of primary cultures of human adipocytes with aldosterone resulted in a
      decrease in the expression of PCK1, PLIN and ADIPOQ and this effect was blocked
      by eplerenone. Therefore, the characteristic aldosterone excess of PA patients
      may mediate the down-regulation of PCK1, PLIN and ADIPOQ in VAT that in turn may
      contribute to the insulin resistance observed in PA patients.

PMID- 22366096
TI  - Preliminary evidences on mitochondrial injury and impaired oxidative metabolism
      in breast cancer.
AB  - Mitochondriopathy is emerging as a new cancer theory; however, the relevance of
      mitochondrial pathobiology in breast cancer has not yet been completely explored.
      Herein we report on altered expression levels of the oxidative phosphorylation
      system (OXPHOS) subunits, mitochondrial structural injury and impaired ATP
      content from a breast-infiltrating ductal carcinoma (IDC). With this purpose, a
      human mammary carcinoma (HMC-1) cell, referred to a human mammary epithelial cell
      (HMEC) line, was assayed for: a) OXPHOS levels by quantitative cryo
      immunoelectron microscopy (CIEM) labeling; b) morphological characterization by a
      newly introduced damage grading (scale Mt-g1-3), calculated on the % of intact
      cristae carrying mitochondria; c) bioenergetic impairment by luminometric
      determinations of cellular ATP content and cytochemical visualization of COX
      activity. Drastic OXPHOS reduction was observed in HMC-1 cells for the succinate
      dehydrogenase complex II SDH-B protein, while decreasing was reported for the
      NADH-ubiquinone oxidoreductase complex I NDUFS3 and the ubiquinol cytochrome c
      reductase complex III UQCRC2 subunits. A significant dropping was detected for
      the ATP-synthase complex V F1beta protein. For the COX complex near-depletion of
      the mitochondrial-encoded COXI and no apparent variation of the COXIV subunits
      were observed. Injury grading was categorized assigning three levels of
      morphological damage in HMC-1 mitochondria: i) severe (4.6%), ii) moderate
      (23.1%), iii) slight (44.6%), corresponding to 0%, 1-50% and 51-75% of area
      occupied by intact cristae. ATP generation and COX activity appeared
      significantly reduced in HMC-1 cells. The structural damage grading here
      described could provide new insight on IDC mitochondrial impairment and represent
      hallmark in the breast cancer mitochondriopathy.

PMID- 22366097
TI  - Critical review of dose-response options for F344 rat mammary tumors for
      acrylamide - additional insights based on mode of action.
AB  - Previous risk assessment reviews analyzed the potential for dietary acrylamide to
      increase breast cancer risk. Here, we critically review acrylamide animal
      bioassay data on mammary tumors for human relevance. We applied a systematic
      evaluation using reasonable standards of scientific certainty and a systematic
      weight of evidence (WOE) approach to evaluate several hypothesized modes of
      action (MOA), including (1) genotoxicity related to glycidamide formation and
      oxidative stress, (2) endocrine effects due to age-related hyperprolactinemia or
      secondary to neurotoxicity, and (3) epigenetic effects. We conclude that the
      appropriate approach for low-dose extrapolation of the rat mammary tumors can be
      narrowed to two options: (1) linear low-dose extrapolation (i.e., based on a MOA
      of mutagenicity from direct DNA interaction) from a point of departure (POD) for
      the combined incidence of adenomas and adenocarcinomas, since these tumor types
      are related; or (2) non-linear extrapolation, using uncertainty factors to
      estimate a Reference Dose (RfD) from a POD for tumor promotion derived using the
      combined fibroadenoma, adenoma and adenocarcinoma data. Non-linear extrapolation
      is used in the latter approach because these combined tumor types are unlikely to
      be exclusively caused by mutagenicity. Comparison of the WOE for each alternative
      MOA indicates that a non-linear approach (option 2) is more appropriate for
      evaluation of acrylamide-induced mammary tumors; a linear approach (option 1) is
      shown for comparison.

PMID- 22366098
TI  - Comparing anti-hyperglycemic activity and acute oral toxicity of three different
      trivalent chromium complexes in mice.
AB  - Three different ligands (rutin, folate and stachyose) of chromium(III) complexes
      were compared to examine whether they have similar effect on anti-hyperglycemic
      activity as well as the acute toxicity status. Anti-hyperglycemic activities of
      chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium
      stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with
      daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute
      toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0
      g/kg with a single oral gavage and observed for a period of 2 weeks. Biological
      activities results indicated that only CrRC and CrFC could decrease blood glucose
      level, reduce the activities of aspartate transaminase, alanine transaminase,
      alkaline phosphatase, and increase liver glycogen level. In acute toxicity study,
      LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose
      for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic
      activity of those chromium complexes was not similar and their acute toxicities
      were also different. CrFC represent an optimal chromium supplement among those
      chromium complexes with potential therapeutic value to control blood glucose in
      diabetes and non-toxicity in acute toxicity.

PMID- 22366099
TI  - Anti-inflammatory activity of hydroxycinnamic acid derivatives isolated from corn
      bran in lipopolysaccharide-stimulated Raw 264.7 macrophages.
AB  - In this study, the effect of the 80% ethanolic extract of corn bran (EECB) on
      inhibition of nitric oxide (NO) production and inducible nitric oxide synthase
      (iNOS) expression in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells was
      investigated. The EECB inhibited LPS-induced NO production and iNOS expression in
      a dose-dependent manner. Four hydroxycinnamic acid derivatives (HADs), including
      two free cinnamic acids, p-coumaric acid (CA) and ferulic acid (FA), and their
      conjugate phenolic amides, p-dicoumaroyl-putrescine (DCP) and
      diferuloylputrescine (DFP), were found to be present in the EECB by LC-MS
      analysis, and DFP (378.66 MUg/g) was the predominant phenolic compound, followed
      by DCP (7.83 MUg/g)>CA (5.58 MUg/g)>FA (1.84 MUg/g). The four HADs significantly
      inhibited NO production and iNOS expression in a dose-dependent manner. Among the
      four HADs tested, DFP showed the most potent inhibition on NO production and iNOS
      mRNA and protein expression, followed by DCP>FA >= CA. DFP also exhibited the
      strongest inhibition on LPS-induced iNOS and NF-kappaB luciferase activity, which
      was followed by DCP >= FA (CA)>CA (FA). Thus, these results suggest that phenolic
      amides in the corn bran may be a potential source of natural anti-inflammatory
      agents.

PMID- 22366100
TI  - Neuroprotective action of bacterial melanin in rats after corticospinal tract
      lesions.
AB  - Experiments were performed on 48 albino rats. Part of the experimental animals
      were initially trained to a balancing instrumental conditioned reflex (ICR).
      Unilateral bulbar pyramidotomy performed in all rats caused contralateral
      hemiparesis. On the next day following the operation 24 rats were injected
      intramuscularly with bacterial melanin solution. 12 of these rats were initially
      trained to ICR. Recovery periods of ICR and paralyzed hindlimb movements were
      registered for melanin injected rats (n=24) and for operated rats, not treated
      with melanin (n=24). In rats injected with bacterial melanin the posttraumatic
      recovery is shorter than in animals not treated with melanin. The fastest and
      complete recovery was registered in rats initially trained to ICR and injected
      after the operation with bacterial melanin. Electrophysiological experiments were
      performed in transected animals treated with melanin, transected animals without
      melanin treatment and intact animals. Spiking activity of motoneurons was
      registered in lumbar motoneurons of rats in response to high frequency
      stimulation above the corticospinal tract transection. Spiking activity was very
      similar in motoneurons of melanin injected and intact or non operated animals. In
      animals, not dosed with bacterial melanin after the operation, areactivity or no
      change in firing rate was registered in response to stimulus. Stimulation of the
      corticospinal tract of melanin injected rats produced potentiation of the
      motoneuronal firing rate and is an evidence of regeneration in corticospinal
      tract. Similarity in spiking activity of intact and melanin injected rats shows
      the recovery of conductance in pyramidal tract. Morphohistochemical examination
      was carried out to confirm the results of behavioral and electrophysiological
      experiments. Medulla slices were prepared to trace the regeneration of nerve
      fibers. Examination of transection area revealed that bacterial melanin increases
      vascularization, dilates the capillaries in nervous tissue and stimulates the
      process of sprouting.

PMID- 22366101
TI  - Comparison of propagation of atrial excitation with the cardiopotential
      distribution on the body surface of hypertensive rats.
AB  - OBJECTIVE: Arterial hypertension is associated with the risk of developing atrial
      arrhythmia. This research was aimed at studying the sequence of depolarization
      along the atrial epicardium and formation of the cardioelectric field on the body
      surface of hypertensive rats. METHODS: The study was carried out on eleven ISIAH
      rats (with hereditary stress-induced hypertension). We analyzed spatial-temporal
      characteristics of body surface potential map (BSPM), time characteristics of
      electrocardiogram during atrial depolarization, sequence of atrial epicardial
      depolarization of rats. Statistical analysis was performed using independent
      samples t-test. RESULTS: The results indicated that in 27% of hypertensive rats
      in the pulmonary vein (PV) sleeves, early excitation areas are formed 2.0 +/- 0.5
      ms after the beginning of depolarization of the sino-atrial node area, in 73% of
      animals, the area of the PV sleeves is excited 6.5 +/- 0.4 ms after the beginning
      of depolarization. In experimental animals, the beginning of inversion of areas
      of positive and negative cardioelectric potentials on BSPM does not differ. In
      73% of rats, duration of inversion on BSPM was 7.7 +/- 1.9 ms, and in 27% - 3.9
      +/- 0.1 ms (p=0.011). The formation of early activation zones in PV of rats with
      arterial hypertension testifies to possible wandering focus in the myocardium of
      PV sleeves. Stress-induced hypertension results in actual risk of atrial
      arrhythmias, which originate at the base of the PV. CONCLUSION: In rats with
      arterial hypertension, two early depolarization zones are revealed in the sinus
      node area and in the PV return to the left atrium, projected on BSPM by mutual
      positions of negative and positive potential zones.

PMID- 22366102
TI  - Correlation of echocardiographic epicardial fat thickness with severity of
      coronary artery disease-an observational study.
AB  - OBJECTIVE: Epicardial fat is an indirect contact with coronary arteries. There
      are some studies about the relationship between this fat and metabolic syndrome
      and it has considered as an indicator of cardiovascular risk. Several studies
      have addressed the association between epicardial fat thickness (EFT) and
      coronary artery disease (CAD) with conflicting results. The aim of our study was
      to evaluate the hypothesis that echocardiographic EFT thickness could be a marker
      severe CAD. METHODS: Overall, 315 cases who underwent coronary angiography were
      classified in two groups: Normal and CAD. Measurement of EFT was done with
      echocardiography. The difference between mean EFT in two groups was analyzed.
      Califf scoring considered for severity of CAD. Then the relationship between EFT
      and age, sex, body mass index (BMI), serum lipids and severity of CAD was
      evaluated. The obtained data were compared by using ANCOVA test, Pearson and
      Spearman's partial correlation analyses. RESULTS: The EFT in CAD group was
      significantly higher than in normal group (5.4 +/- 1.9 mm vs 4.4 +/- 1.8 mm,
      p=0.0001). EFT had a positive relationship with Califf scoring of diseased
      coronary arteries (r=0.158 p=0.04), low-density lipoprotein cholesterol (p=0.04),
      female gender (p=0.02), BMI (p=0.001) and serum triglyceride levels (p=0.04).
      CONCLUSION: This study shows an association between EFT thickness and severity of
      CAD.

PMID- 22366103
TI  - Is increased epicardial fat thickness a marker of the presence of severe coronary
      artery disease?

PMID- 22366104
TI  - An observational study of the effect of coronary artery disease severity on acute
      pacing threshold and lead impedance in patients with permanent pacemaker.
AB  - OBJECTIVE: This study investigated the effect of coronary artery disease (CAD)
      severity, distribution and left ventricular ejection fraction (LVEF) on acute
      ventricular pacing threshold and lead impedance at the time of pacemaker
      implantation. METHODS: One hundred and thirty-two patients who received a
      ventricular pacemaker or internal cardioverter-defibrilator (ICD) lead in our
      institution between 2007-2010 were included in this observational study. Patients
      were divided into ICD and anti-bradycardic pacemaker (PM) groups. Groups were
      compared for ventricular stimulation threshold, lead impedance and LVEF. Later,
      groups were sub-grouped according to the severity and distribution of CAD and
      subgroups were compared in both groups for ventricular stimulation threshold,
      lead impedance. Quantitative data of groups were compared by means of independent
      samples t-test. RESULTS: Ventricular pacing thresholds were found significantly
      higher ICD group compared with PM group (p<0.05). Impedance and LVEF values were
      significantly lower in ICD group (p<0.05). Impedance and ventricular pacing
      thresholds were comparable in subgroups of ICD and PM groups. Our study does not
      confirm any relationship between pacing parameters and severity-distribution of
      CAD and LVEF. CONCLUSION: Patients with ventricular ICD lead had higher pacing
      thresholds but lower pacing impedance values comparing with PM group. This study
      did not find any significant relationship between pacing parameters at
      implantation and LVEF, severity and distribution of CAD.

PMID- 22366105
TI  - Clinical effects of enhanced external counterpulsation treatment in patients with
      ischemic heart failure.
AB  - OBJECTIVE: Enhanced external counterpulsation (EECP) is a noninvasive treatment
      that is proven safe and effective in patients with coronary artery disease (CAD)
      and heart failure (HF). The aims of this study are to investigate the clinical
      effects of EECP therapy in patients with symptomatic CAD and chronic HF, and to
      find out an answer to the question: Does EECP therapy have any effect on the
      prognostic markers of HF? METHODS: This study was designed as a prospective
      cohort study. A total of 68 consecutive patients with symptomatic CAD and chronic
      HF referred to EECP therapy were enrolled in this study between November 2007 and
      December 2010; 47 patients (39 males and 8 females, 65 +/- 7, years), have
      undergone EECP treatment, and 21 patients (20 males and 1 female, 62 +/- 10
      years), who did not want to participate in the EECP program comprised the control
      group. Statistical analysis was performed using t tests for dependent and
      independent samples, Mann-Whitney U test, Chi-square and Fischer exact tests.
      RESULTS: EECP therapy resulted in significant Improvement in post-intervention
      New York Heart Association functional class (p<0.001), left ventricular ejection
      fraction (p<0.001), B-type natriuretic peptide levels (p<0.003), uric acid levels
      (p<0.05), free-T3/free-T4 ratio (p<0.034) and mitral annular E (p<0.05) velocity,
      compared with baseline, a finding not evident in the control group. CONCLUSION:
      EECP treatment significantly improved clinical and some biochemical parameters,
      which are mostly prognostic markers in patients with symptomatic CAD and chronic
      HF.

PMID- 22366107
TI  - Ambulation following cardiac catheterization: the earlier the better.

PMID- 22366106
TI  - Effect of early ambulation after transfemoral cardiac catheterization in Hong
      Kong: a single-blinded randomized controlled trial.
AB  - OBJECTIVE: The purpose of the study was to investigate the effect of early
      ambulation after cardiac catheterization (CC) on patients' back pain, puncture
      site pain, vascular complications, urinary discomfort, general well-being
      perception and satisfaction level. METHODS: This study was a randomized single
      blinded controlled trial. Overall, 137 participants were randomly assigned to
      experimental (63 participants) or control (74 participants) group according to a
      computer generated random list. Early ambulation (ambulate at 4 hours post-CC)
      and routine post-procedure care of 12 to 24 hours were used in the experimental
      and control groups respectively. Independent t-test, Chi-square test, multiple
      logistic regression and generalized estimation equation model were applied to
      compare various outcomes between experimental and control groups. RESULTS: Only
      one patient in the control group experienced puncture site bleeding after CC.
      Ambulation at 4 hours after CC significantly reduced patients' back pain 8 hours
      after they returned to the unit (OR=0.19, 95% CI: 0.08-0.45, p<0.001) and in the
      next morning (OR=0.36, 95% CI: 0.15-0.87, p=0.023), decrease urinary discomfort
      (OR=0.35, 95% CI: 0.14-0.90, p=0.03 for "very or unbearable urination discomfort"
      and OR=0.22, 95% CI: 0.06-0.74, p=0.015 for "much difficulty or unable to urinate
      at all"), and increase general well- being (p=0.005 for vitality subscale and
      p=0.014 for the total general well-being). However, it made no significant
      differences on puncture site pain as well as the satisfaction level of patients.
      CONCLUSION: The study enhanced health providers' understanding about the effects
      of early ambulation on patient outcomes. Nurses may provide more individualized
      and appropriate care to post-CC patients in a more competent and cost-effective
      way.

PMID- 22366108
TI  - Inhibition of pyrimidine and purine nucleoside phosphorylases by a 3,5
      dichlorobenzoyl-substituted 2-deoxy-D-ribose-1-phosphate derivative.
AB  - The 3,5-dichlorobenzoyl-substituted 2-deoxy-D-ribose-1-phosphate derivative,
      designated Cf2891, was found to inhibit a variety of pyrimidine and purine
      nucleoside phosphorylases (NPs) with preference for uridine- and inosine
      hydrolyzing enzymes [uridine phosphorylase (UP; EC 2.4.2.3), pyrimidine
      nucleoside phosphorylase (PyNP; EC 2.4.2.2) and purine nucleoside phosphorylase
      (PNP; EC 2.4.2.1)]. Kinetic analyses revealed that Cf2891 competes with inorganic
      phosphate (P(i)) for binding to the NPs and, depending on the nature of the
      enzyme, acts as a competitive or non-competitive inhibitor with regard to the
      nucleoside binding site. Also, the compound prevents breakdown of pyrimidine
      analogues used in the treatment of viral infections and cancer. Since NPs are
      abundantly present in tumor tissue and may be overexpressed due to secondary
      bacterial infections in immunocompromised patients suffering viral infections,
      Cf2891 may serve as a lead molecule for the development of inhibitors to be used
      in nucleoside-based combination therapy.

PMID- 22366110
TI  - Characterization of desoxymethyltestosterone main urinary metabolite produced
      from cultures of human fresh hepatocytes.
AB  - Desoxymethyltestosterone (DMT; 17beta-hydroxy-17alpha-methyl-5alpha-androst-2
      ene) is a designer steroid present in hormonal supplements distributed illegally
      as such or in combination with other steroids, for self-administration. It
      figures on the list of substances prohibited in sports and its detection in
      athlete's urine samples is based upon the presence of the parent compound or the
      main urinary metabolite, which has not been characterized yet. Following its
      isolation from cultures of human fresh hepatocytes and S9 fractions of liver
      homogenates, we were able to identify this metabolite as being 17alpha-methyl
      2beta,3alpha,17beta-trihydroxy-5alpha-androstane. Other minor metabolites were
      also characterized. The production, isolation, NMR, mass spectral analyses and
      chemical synthesis are presented.

PMID- 22366109
TI  - Misexpression screen delineates novel genes controlling Drosophila lifespan.
AB  - In an initial preliminary screen we identified factors associated with
      controlling Drosophila aging by examining longevity in adults where EP elements
      induced over-expression or antisense-RNA at genes adjacent to each insertion.
      Here, we study 45 EP lines that initially showed at least 10% longer mean
      lifespan than controls. These 45 lines and a daughterless (da)-Gal4 stock were
      isogenized into a CS10 wild-type background. Sixteen EP lines corresponding to 15
      genes significantly extended lifespan when their target genes were driven by da
      Gal4. In each case, the target genes were seen to be over-expressed.
      Independently derived UAS-gene transgenic stocks were available or made for two
      candidates: ImpL2 which is ecdysone-inducible gene L2, and CG33138, 1,4-alpha
      glucan branching enzyme. With both, adult lifespan was increased upon over
      expression via the GeneSwitch inducible Gal4 driver system. Several genes in this
      set of 15 correspond to previously discovered longevity assurance systems such as
      insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new
      potential mechanisms for the control of aging including mRNA synthesis and
      maturation, intracellular vesicle trafficking, and neuroendocrine regulation.

PMID- 22366111
TI  - The role of the human ventral striatum and the medial orbitofrontal cortex in the
      representation of reward magnitude - an activation likelihood estimation meta
      analysis of neuroimaging studies of passive reward expectancy and outcome
      processing.
AB  - Reward maximization is a core motivation of every organism. In humans, several
      brain regions have been implicated in the representation of reward magnitude.
      Still, it is unclear whether identical brain regions consistently play a role in
      reward prediction and its consumption. In this study we used coordinate-based ALE
      meta-analysis to determine the individual roles of the ventral striatum (vSTR)
      and the medial orbitofrontal cortex (mOFC/VMPFC) in the representation of reward
      in general and of reward magnitude in particular. Specifically, we wanted to
      assess commonalities and differences in regional brain activation during the
      passive anticipation and consumption of rewards. Two independent meta-analyses of
      neuroimaging data from the past decade revealed a general role for the vSTR in
      reward anticipation and consumption. This was the case particularly when the
      consumed rewards occurred unexpectedly or were uncertain. In contrast, for the
      mOFC/VMPFC the present meta-analytic data suggested a rather specific function in
      reward consumption as opposed to passive anticipation. Importantly, when
      considering only coordinates that compared different reward magnitudes, the same
      parts of the vSTR and the mOFC/VMPFC showed concordant responses across studies,
      although areas of coherence were regionally more confined. These meta-analytic
      data suggest that the vSTR may be involved in both prediction and consumption of
      salient rewards, and may also be sensitive to different reward magnitudes, while
      the mOFC/VMPFC may rather process the magnitude during reward receipt.
      Collectively, our meta-analytic data conform with the notion that these two brain
      regions may subserve different roles in processing of reward magnitude.

PMID- 22366112
TI  - An experimental evaluation of an effective medium based compaction equation.
AB  - Tablet production involves compression of free flowing powder in an enclosed
      cavity of defined geometry. The complexity of the powder bed system necessitates
      that a way be found to better understand what occurs during compression. One such
      approach is by means of compaction equations, of which, the Heckel and Kawakita
      equations are the best known. This work attempts to experimentally evaluate the
      applicability of the effective medium (EM) equation introduced by Frenning et al.
      (2009) to powder systems. Two powder types (sodium chloride and lactose
      monohydrate), each consisting of three size fractions (<40, 125-212 and 212
      300MUm) were characterised and compressed to a pressure of 500MPa. These powders
      were chosen because of their differing mechanical properties. An invariance which
      is inherent in the EM equation is exposed by varying the starting points of
      compression, and can yield insights into compression mechanisms. Such invariant
      regions were observed once plastic particle deformation started to dominate the
      compression behaviour, and enabled the determination of the point where particle
      rearrangement stops.

PMID- 22366113
TI  - Early undernutrition is associated with attenuated inflammatory response and
      alteration in pharmacological efficacy of indomethacin in rats.
AB  - AIM: The intent of this study is to examine whether intrauterine malnutrition
      provokes alterations in the progression of the acute and subchronic inflammatory
      response, and its influence on the pharmacological effect of indomethacin.
      METHODS DESIGN: Rat offspring of dams which were fed from the first day of their
      gestation to term receiving a balanced diet (Labina) or a basic regional diet
      (BRD) from northeastern Brazil. According to their dams, the offspring were
      divided in two groups: Control-N (nourished) and BRD-g (undernourished during
      gestation). At 2 months of age, the animals were divided into groups (n=06): (1)
      Animals that were subjected to carrageenan or (2) zymosan-induce paw edema (acute
      inflammation models) and (3) Animals that were subjected to cotton pellet-induced
      granuloma (subchronic inflammation model). All animals received (saline 0.9%;
      p.o.). Another set of adult offspring was submitted to the same procedure as
      above, but instead of saline they received (via gavage) a single oral dose of
      indomethacin (10mg/kg) for the animals subjected to acute inflammation models or
      2mg/kg for seven consecutive days for the animals subjected to subchronic
      inflammation model. The animals were further divided in two groups: Control-NI
      (Control-N treated with indomethacin), and BRDI-g (BRD-g treated with
      indomethacin). The volume of hind paw swelling (mL) was measured at time zero
      (before), 30, 60, 120, 180 and 240 min after carrageenan or zymosan injection. In
      the subchronic model of inflammation, the pellets were removed and dried to a
      constant weight. Hind paw swelling, weight of granuloma, blood albumin and C
      reactive protein (CRP) levels, leukocyte count and cytokine levels were evaluated
      as indicators of inflammation. RESULTS: Undernutrition during pregnancy caused
      fetal growth retardation which was shown in terms of low birth weight (5.38+/
      0.28), when compared to the Control-N (7.26+/-0.64) group. The volume of paw
      edema, the serum levels of CRP and albumin and cytokine levels were lower than
      those in the BRD-g group when compared to those in the Control-N groups, in both
      models of acute inflammation studied. However, no difference was found in the
      total leukocyte count. When compared to the respective groups treated with saline
      (Control-N and BRD-g), the antiinflammatory effect of indomethacin in the animals
      of BRDI-g groups was lower than in the Control-NI groups, in the model of acute
      inflammation. In the model of subchronic inflammation, the pharmacological effect
      of indomethacin was effective only in nourished animals. CONCLUSION: Malnutrition
      in the early stages of development attenuated the severity of the acute
      inflammatory response, but there was no statistically significant change in
      subchronic inflammation induced by granulomatous lesion. Our findings provide
      impetus for larger trials to assess the influence of undernutrition on the
      pharmacokinetics/pharmacodynamics of indomethacin.

PMID- 22366114
TI  - Vaccines in non-small cell lung cancer: rationale, combination strategies and
      update on clinical trials.
AB  - Non-small cell lung cancer (NSCLC) remains the leading cause of cancer related
      mortality worldwide and despite some advances in therapy the overall prognosis
      remains disappointing. New therapeutic approaches like vaccination have been
      proposed and several clinical trials are ongoing. Many tumor antigens have been
      identified so far and specific tumor vaccines targeting these antigens have been
      developed. Even if the ideal setting for vaccine therapy might be the adjuvant
      one, vaccines seem to be potentially beneficial also in advanced disease and
      combination therapy could be a promising treatment option. In the advanced
      setting anti-MUC-1 vaccine (belagenpumatucel) and anti-TGF-beta(2) vaccine (BPL
      25) have entered in phase III trials as maintenance therapy after first line
      chemotherapy. In the adjuvant setting the most relevant and promising vaccines
      are directed against MAGE-A3 and PRAME, respectively. We will review the key
      points for effective active immunotherapies and combination therapies, giving an
      update on the most promising vaccines developed in NSCLC.

PMID- 22366115
TI  - Surveillance for hereditary cancer: does the benefit outweigh the psychological
      burden?--A systematic review.
AB  - Individuals at risk for developing hereditary cancer are offered surveillance in
      order to improve the prognosis. An important question is whether the benefit of
      surveillance outweighs the psychological burden. In this review, we evaluated all
      studies that investigated psychological distress and the quality of life in
      individuals under surveillance for hereditary cancer of the breast, ovarian,
      prostate, pancreas, colorectum, melanoma, and various rare syndromes such as
      familial adenomatous polyposis, Li-Fraumeni and Peutz-Jeghers syndrome. Thirty
      two studies were identified. Surveillance for most hereditary cancers was
      associated with good psychological outcomes. However, surveillance of individuals
      at high risk for developing multiple tumors appeared to be associated with
      increased distress and a lower quality of life. Common factors associated with
      worse psychological outcomes included a personal history of cancer, female
      gender, having a first degree relative with cancer, negative illness perceptions
      and coping style. The use of a simple screening tool to identify distressed
      individuals is recommended.

PMID- 22366116
TI  - A short-term toxicity study of Aspergillus carbonarius carotenoid.
AB  - In a pharmacokinetic study, high-performance liquid chromatography analysis of
      blood samples of Wistar female rats fed with partially saturated canthaxanthin
      (PSC) of Aspergillus carbonarius showed the presence of the carotenoid in the
      plasma within 6 hours of feeding. In another study for safety assessment of PSC
      fed to rats over a period of 28 days at 0.05%, 0.10%, and 0.25%, the rats showed
      no changes in food intake. There were no significant differences observed in body
      weight, hematological parameters, or serum clinical enzymes compared to the
      control group not fed with PSC. Deposition of PSC in the eyes of the rats was
      also not observed. The results showed that PSC-fed rats were not adversely
      affected as far as toxicological studies were concerned.

PMID- 22366118
TI  - Percutaneous closure of mitral paravalvular leaks in patients with aortic valve
      prostheses.

PMID- 22366117
TI  - Interacting sites of scorpion toxin ErgTx1 with hERG1 K+ channels.
AB  - Peptides purified from scorpion venoms were shown to interact with specific amino
      acid residues present in the outer vestibule of various sub-types of potassium
      channels, occluding the pore and causing a decrement of K(+) permeability through
      the membrane of excitable and non excitable cells. This communication describes
      the identification of several interacting sites of toxin ErgTx1, a toxin purified
      from the venom of the scorpion Centruroides noxius, with the human ERG1 K(+)
      channels, by means of site-directed mutagenesis of specific residues of the
      toxin. Recombinant mutants of the gene coding for ErgTx1 were expressed
      heterologously in Escherichia coli, properly folded and their affinities and
      interactions with hERG1 channels were determined by patch-clamp techniques.
      Residues in position Y14, Y17 and F37 of the solvent exposed hydrophobic surface,
      and charged residues at the position K13 and K38 of ErgTx1 were shown to cause a
      decrement of the affinity from 20 folds to 3 orders of magnitude, thus suggesting
      that they are certainly participating on the binding surface of this toxin
      towards the hERG1 channels. Double mutants at positions K13 and F37, Y14 and F37,
      Y17 and F37 and K13 and K38 were also prepared and assayed, but the results
      obtained are not much different from the single point mutants of ErgTx1. The
      results of the present work indicate the most probable surface area of ErgTx1
      that makes contact with the hERG channels.

PMID- 22366119
TI  - Characteristics of alcoholics attending 'clubs of alcoholics in treatment' in
      Italy: a national survey.
AB  - AIMS: To provide an overview of alcoholics attending a socio-ecological treatment
      programme [Clubs of Alcoholics in Treatment (CATs)] and to identify factors
      associated with abstinence and self-perceived improvement in lifestyle. METHODS:
      A national sample of 7522 subjects (76% males and 24% females, mean age 53.2 +/-
      11.3 years +/- SD) attending CATs was evaluated using a self-administered
      questionnaire completed at a weekly meeting in 2006. RESULTS: Of participants,
      >70% reported no alcohol use in the last year and around 90% indicated no use in
      the previous month, whereas 4% of them declared no alcohol use before club
      attendance. Abstinence and lifestyle improvement were related positively to the
      number of years of club attendance but negatively to the presence of other
      problems in addition to the alcohol-related one. Moreover, being older or female
      was associated with more likely achievement of abstinence as well as with the
      perception of a better lifestyle. Finally, attending the club with one or more
      family members was associated with achievement of better lifestyle. CONCLUSION:
      These data provide an overview of alcoholics attending the CAT programme and are
      a first step toward developing a surveillance system. In addition, on the basis
      of this preliminary picture further research (notably longitudinal studies) can
      be planned considering this method and its effectiveness.

PMID- 22366120
TI  - Changes in insulin sensitivity during GnRH agonist treatment in premenopausal
      women with leiomyoma.
AB  - OBJECTIVE: The purpose of this study was to determine (1) the influence of
      estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist
      administration on insulin sensitivity as well as hormones and factors related to
      insulin resistance and (2) the differences in the influence for these parameters
      by the degree of basal insulin sensitivity. METHODS: Thirty-five women diagnosed
      with leiomyoma were enrolled in this study. Serum levels of fasting glucose,
      insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular
      inflammatory markers and cytokines before and at 6months after commencement of
      GnRH agonist administration were examined. RESULTS: In all women, levels of
      insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR)
      were not significantly changed. However, in women who had a low HOMA-IR before
      treatment, levels of insulin, glucose and HOMA-IR showed significant increases
      and total testosterone level showed a significant decrease. In women who had a
      high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased
      and levels of highly sensitive C-reactive protein, soluble intercellular adhesion
      molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly
      increased. CONCLUSION: Change in insulin sensitivity caused by GnRH agonist
      administration for premenopausal women with leiomyoma differs depending on
      baseline insulin sensitivity before treatment.

PMID- 22366121
TI  - Interference of urinary amino acid analysis by pregabalin.

PMID- 22366122
TI  - Comparison of novel pro-BNP(1-108) and standard BNP assays in heart failure
      patients.
AB  - BACKGROUND: Heart failure (HF) progression and outcomes reflect activation of
      multiple neurohormonal systems. Which biomarkers reflecting these systems
      contribute incremental information remains unclear. The aim of this study was to
      determine if serial measurements of pro-BNP(1-108) separately, in combination
      with standard assay BNP, or with troponin T (cTnT) would enhance risk
      stratification in ambulatory HF patients. METHODS: A cohort of 187 Class III-IV
      HF patients was prospectively studied. Blood was collected every 3 months over 2
      years for biomarker analysis [pro-BNP(1-108), standard assay BNP, troponin T
      (cTnT)] in relation to the primary endpoint of death or cardiac transplantation.
      RESULTS: Univariate categorical and continuous variable analyses of single-sample
      and time-dependent serial values of pro-BNP(1-108) and BNP demonstrated that
      elevations in both biomarkers were associated with increased risk of
      death/transplantation. Multivariate analysis of serial measurements adjusted for
      cTnT revealed cTnT as the independent marker of risk. Combined elevations of
      either pro-BNP(1-108) or BNP with cTnT, however, were the most significant
      predictors of outcome. CONCLUSIONS: Circulating levels of pro-BNP(1-108) appear
      to be comparable to mature BNP in ambulatory HF out-patients. Elevated levels of
      pro-BNP(1-108) or BNP identified by serial monitoring similarly predict events. A
      strategy of serial monitoring of either pro-BNP(1-108) or BNP alone or
      particularly in combination with cTnT can serve a valuable role in detecting
      higher-risk HF patients.

PMID- 22366123
TI  - Does cultural integration explain a mental health advantage for adolescents?
AB  - BACKGROUND: A mental health advantage has been observed among adolescents in
      urban areas. This prospective study tests whether cultural integration measured
      by cross-cultural friendships explains a mental health advantage for adolescents.
      METHODS: A prospective cohort of adolescents was recruited from 51 secondary
      schools in 10 London boroughs. Cultural identity was assessed by friendship
      choices within and across ethnic groups. Cultural integration is one of four
      categories of cultural identity. Using gender-specific linear-mixed models we
      tested whether cultural integration explained a mental health advantage, and
      whether gender and age were influential. Demographic and other relevant factors,
      such as ethnic group, socio-economic status, family structure, parenting styles
      and perceived racism were also measured and entered into the models. Mental
      health was measured by the Strengths and Difficulties Questionnaire as a 'total
      difficulties score' and by classification as a 'probable clinical case'. RESULTS:
      A total of 6643 pupils in first and second years of secondary school (ages 11-13
      years) took part in the baseline survey (2003/04) and 4785 took part in the
      follow-up survey in 2005-06. Overall mental health improved with age, more so in
      male rather than female students. Cultural integration (friendships with own and
      other ethnic groups) was associated with the lowest levels of mental health
      problems especially among male students. This effect was sustained irrespective
      of age, ethnicity and other potential explanatory variables. There was a mental
      health advantage among specific ethnic groups: Black Caribbean and Black African
      male students (Nigerian/Ghanaian origin) and female Indian students. This was not
      fully explained by cultural integration, although cultural integration was
      independently associated with better mental health. CONCLUSIONS: Cultural
      integration was associated with better mental health, independent of the mental
      health advantage found among specific ethnic groups: Black Caribbean and some
      Black African male students and female Indian students.

PMID- 22366124
TI  - Presence of a large beta(1-3)glucan linked to chitin at the Saccharomyces
      cerevisiae mother-bud neck suggests involvement in localized growth control.
AB  - Previous results suggested that the chitin ring present at the yeast mother-bud
      neck, which is linked specifically to the nonreducing ends of beta(1-3)glucan,
      may help to suppress cell wall growth at the neck by competing with beta(1
      6)glucan and thereby with mannoproteins for their attachment to the same sites.
      Here we explored whether the linkage of chitin to beta(1-3)glucan may also
      prevent the remodeling of this polysaccharide that would be necessary for cell
      wall growth. By a novel mild procedure, beta(1-3)glucan was isolated from cell
      walls, solubilized by carboxymethylation, and fractionated by size exclusion
      chromatography, giving rise to a very high-molecular-weight peak and to highly
      polydisperse material. The latter material, soluble in alkali, may correspond to
      glucan being remodeled, whereas the large-size fraction would be the final cross
      linked structural product. In fact, the beta(1-3)glucan of buds, where growth
      occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan
      elongation showed a large increase in the polydisperse fraction. By a procedure
      involving sodium hydroxide treatment, carboxymethylation, fractionation by
      affinity chromatography on wheat germ agglutinin-agarose, and fractionation by
      size chromatography on Sephacryl columns, it was shown that the beta(1-3)glucan
      attached to chitin consists mostly of high-molecular-weight material. Therefore,
      it appears that linkage to chitin results in a polysaccharide that cannot be
      further remodeled and does not contribute to growth at the neck. In the course of
      these experiments, the new finding was made that part of the chitin forms a
      noncovalent complex with beta(1-3)glucan.

PMID- 22366125
TI  - Role of ATG8 and autophagy in programmed nuclear degradation in Tetrahymena
      thermophila.
AB  - Autophagy is an evolutionarily conserved mechanism for the degradation of
      cellular components, but its role in enucleation during differentiation has not
      been established. Tetrahymena thermophila is a unicellular eukaryote with two
      functionally distinct nuclei, the somatic (macro-) and the germ line (micro-)
      nuclei. These nuclei are produced during sexual reproduction (conjugation), which
      involves differentiation and selective degradation of several specific nuclei. To
      examine the role of autophagy in nuclear degradation, we studied the function of
      two ATG8 genes in Tetrahymena. Through fluorescent protein tagging, we found that
      both proteins are targeted to degrading nuclei at specific stages, with some
      enrichment on the nuclear periphery, suggesting the formation of autophagosomes
      surrounding these nuclei. In addition, ATG8 knockout mutant cells showed a
      pronounced delay in nuclear degradation without apparently preventing the
      completion of other developmental events. This evidence provided direct support
      for a critical role for autophagy in programmed nuclear degradation. The results
      also showed differential roles for two ATG8 genes, with ATG8-65 playing a more
      significant role in starvation than ATG8-2, although both are important in
      nuclear degradation.

PMID- 22366126
TI  - Cellular, biochemical, and molecular changes during encystment of free-living
      amoebae.
AB  - Free-living amoebae are protozoa found in soil and water. Among them, some are
      pathogenic and many have been described as potential reservoirs of pathogenic
      bacteria. Their cell cycle is divided into at least two forms, the trophozoite
      and the cyst, and the differentiation process is named encystment. As cysts are
      more resistant to disinfection treatments than trophozoites, many studies focused
      on encystment, but until recently, little was known about cellular, biochemical,
      and molecular modifications operating during this process. Important signals and
      signaling pathways at play during encystment, as well as cell responses at the
      molecular level, have been described. This review summarizes our knowledge and
      focuses on new findings.

PMID- 22366127
TI  - [Slow onset septic arthritis by Scedosporium apiospermum after periarticular
      infiltration].
AB  - BACKGROUND: Fungal arthritis is usually of haematogenous origin, and mainly
      affects patients with impaired cellular immunity or users of intravenous drugs.
      The infection in immunocompetent patients is generally caused by direct
      inoculation of the microorganism through an invasive device. The experience of
      azole therapy in these patients is limited. CASE REPORT: We report a case of
      arthritis caused by Scedosporium apiospermum characterized by its slow onset,
      lack of response to posaconazole and caspofungin, and its successful resolution
      after surgical debridement and treatment with voriconazole. CONCLUSIONS:
      Treatment with voriconazole and surgical debridement is an effective therapy for
      arthritis due to S. apiospermum.

PMID- 22366128
TI  - Allelic types of long polar fimbriae in bovine and human Escherichia coli O157
      strains.
AB  - Long polar fimbriae (Lpf) are recently discovered adhesins and increasingly
      important genetic markers of pathogenic Escherichia coli strains. The presence
      and genotype diversity of Lpf operons was screened in a collection of 97
      Escherichia coli O157 strains representing different pathotypes, isolated from
      healthy cattle (n = 43) and human patients (n = 54) in several countries.
      Individual structural genes of Lpf were scanned by PCR, and allelic variants were
      detected with a recently developed typing scheme. Ninety-five strains carried at
      least one whole Lpf operon (genes lpfABCD and/or lpfABCDE). The 64
      enterohaemorrhagic (EHEC) and 24 enteropathogenic (EPEC) strains all carried two
      Lpf operons, allele 3 of lpfA1 and allele 2 of lpfA2, a combination
      characteristic of the O157:H7/NM serotype. Out of the 9 bovine atypical (AT; stx
      , eae-) strains, 7 carried one complete Lpf operon, allele 1 of lpfA2. The
      atypical strains belonged to main phylogenetic groups A and B1, while the EHEC
      and EPEC strains were from group D. Lpf variants carried by the 72 strains of the
      Escherichia coli Reference Collection (ECOR) were determined with the same typing
      scheme. Alleles were detected in 25 strains, of which 6 were found negative for
      the respective Lpf operons in earlier studies. The marker value of the Lpf
      allelic combination for the O157:H7/NM serotype was confirmed, and further
      evidence was given for the presence of at least two different genetic lineages of
      atypical bovine E. coli O157 strains.

PMID- 22366129
TI  - Genomic and genetic aspects of heart failure in dogs - a review.
AB  - The most common causes of heart failure in dogs are valvular disease,
      predominantly endocardiosis, and myocardial disease, predominantly dilated
      cardiomyopathy. They are related to changes in the expression of several genes in
      the heart muscle and in peripheral blood nuclear cells which could be considered
      as prognostic or diagnostic markers of heart disease in dogs. Since many human
      genetic markers of heart failure have turned out to be useless in dogs, the
      screening for genomic markers of canine heart failure could give more insight
      into the molecular pathology of these diseases and aid the development of new
      treatment strategies.

PMID- 22366130
TI  - Evaluation of EnSeal(r), an adaptive bipolar electrosurgical tissue-sealing
      device.
AB  - Relatively few, and inconsistent, data are available in the literature about the
      properties of EnSeal(r), an electrosurgical tissue-sealing device. For this
      reason, we conducted control safety tests on experimental pigs. The mean burst
      pressure of sealed vessels (2-7 mm in diameter) proved to be 873.89 +/- 120.57
      mmHg (n = 60). Surface temperature increased to 69.25 +/- 0.98  degrees C in
      average (n = 22). The mean diameter of the collateral microscopic thermal injury
      zone was found to be 0.28 +/- 0.04 mm, and it did not show significant
      differences among the groups of tissues studied (n = 183). During our studies,
      the device worked reliably and met the relevant requirements in all cases. It can
      be established that EnSeal(r) enables high-safety clinical interventions at high
      blood pressure values, in different tissues and even at sites adjacent to heat
      sensitive tissues, and thus it paves the way for new operative solutions in both
      human and veterinary surgery. In our opinion, the discrepancies between data
      reported in the literature arise from differences in the design of studies and in
      the designated limit values. To ensure standardisation, we recommend the use of
      the nitroblue-tetrazolium chloride/lactate dehydrogenase (NBTC/LDH) enzyme
      histochemical technique for studying thermal injury induced by the different
      performance levels and application times of devices operating with
      electromagnetic energy.

PMID- 22366131
TI  - Laparoscopic cryptorchidectomy and ovariectomy in standing horses using the
      EnSeal(r) tissue-sealing device.
AB  - In the present series of cases, 8 laparoscopic cryptorchidectomies and 4
      laparoscopic ovariectomies were carried out in sedated standing horses. Sedation
      involved a lesser anaesthesiological risk than does general anaesthesia. As
      compared to laparotomic exposure, the minimally invasive laparoscopic
      intervention provided better visualisation, shorter operative time and faster
      recovery. The blood vessels supplying the testes and ovaries and the suspensory
      ligaments of the organs were sealed and cut with EnSeal(r), an adaptive bipolar
      electrosurgical blood vessel- and tissue-sealing device. The clinical use of the
      blood vessel- and tissue-sealing device proved to be successful in all cases.
      Gradual separation of the intact tissue from the treated, compacted, dehydrated
      and homogenised tissue areas and occlusion of the lumen of blood vessels treated
      with the device could be observed in all histological sections. To the best of
      our knowledge, this is the first report on the use of EnSeal(r) for laparoscopic
      cryptorchidectomy and ovariectomy in horses.

PMID- 22366132
TI  - Clinical factors determining the efficacy of urinary bladder tumour treatments in
      dogs: surgery, chemotherapy or both?
AB  - In a study of 44 canine patients suffering from histopathologically proven
      urinary bladder tumour with a high incidence of transitional cell carcinoma (TCC)
      (n = 35), a close relationship was found either between the disease-free period
      and the age (r = -0.40) of animals or between the survival times and the age (r =
      -0.62) of animals after treatment. In addition to the dog breeds known to be
      prone to have urinary bladder tumour, we found an additional potentially
      sensitive breed, the Hungarian Vizsla. The median survival times obtained by the
      applied treatment types were as follow: 'surgery and chemotherapy' (n = 8/44) 475
      days, 'surgery alone' (n = 19/44) 240 days, 'chemotherapy alone' (n = 7/44) 31
      days, and 'no treatment' (n = 10/44) 7 days (P < 0.001). According to the
      findings, chemotherapy combined with surgery completed in time is the most
      effective protocol in the treatment of urinary bladder tumour cases in dogs. A
      rational and more effective procedure for the assessment and treatment of urinary
      bladder tumour cases is presented.

PMID- 22366133
TI  - Remarks on the seasonal occurrence and identification of young plasmodial stages
      of Myxobolus spp. infecting cyprinid fishes in Hungary.
AB  - During a survey on the Myxobolus infection of two cyprinid fishes, the ide
      (Leuciscus idus) and the roach (Rutilus rutilus), myxosporean developmental
      stages were found around the arteries of the gill filaments and in the gill
      lamellae. An analysis of the 18S rDNA sequences of these stages revealed that
      plasmodia developing in the ide belonged to Myxobolus elegans, those developing
      in the gill lamellae of the roach corresponded to M. intimus, while plasmodia
      developing in close contact with the cartilaginous gill rays proved to be
      developmental stages of M. feisti. A strict seasonal cycle with a very long
      intrapiscine development was recorded for M. elegans and M. intimus. Developing
      plasmodia of the latter Myxobolus spp. occurred from early summer to next spring,
      and spore formation took place only in April. No seasonality associated with M.
      feisti infections was found. Developing plasmodia and mature spores of this
      species occurred simultaneously in different seasons of the year. Myxobolus
      feisti spore formation always occurred in close contact with the cartilaginous
      tissue of the gill filaments but spores were rarely encapsulated in the
      cartilaginous gill rays.

PMID- 22366134
TI  - Survey of nine abortifacient infectious agents in aborted bovine fetuses from
      dairy farms in Beijing, China, by PCR.
AB  - Abortion in dairy cattle causes considerable economic losses to the dairy
      industry. Aborted fetuses and samples from the corresponding aborting dams from
      12 dairy herds in Beijing were tested for 9 abortifacient infectious pathogens by
      PCR between 2008 and 2010. From a total of 80 abortion cases collected during
      this period, infectious agents were detected in 45 (56.3%) cases, 22 (48.9%) of
      which represented co-infections with two or three infectious agents. The detected
      pathogens included infectious bovine rhinotracheitis virus (36.3%) and Neospora
      caninum (31.3%), followed by bovine viral diarrhoea virus (7.5%), Brucella
      abortus (6.3%), Tritrichomonas foetus (5%) and Toxoplasma gondii (1.3%).
      Campylobacter fetus, Coxiella burnetii and Chlamydophila psittaci were not
      detected in any abortion case. Findings from this study indicated that infectious
      bovine rhinotracheitis virus and Neospora caninum were the main potential causes
      of abortions in Beijing dairy herds, whereas the bacterial pathogens were not, in
      contrast to reports from other countries. This is the first study to test nine
      abortifacient infectious agents by PCR at the same time, and it is also the first
      time to report the involvement of a variety of infectious agents in bovine
      abortion cases in China.

PMID- 22366135
TI  - Effects of short-term sodium chlorate exposure on pigs.
AB  - The present study evaluated the effects of exposure to different doses of sodium
      chlorate in 10-week-old pigs. Twenty pigs were divided into four equal groups and
      treated with different doses of sodium chlorate: 0, 125, 250 and 500 mg kg-1 body
      weight per day via the drinking water for 7 consecutive days. The results showed
      a significant decrease (P < 0.05) in red blood cell and white blood cell counts,
      packed cell volume, haemoglobin, blood urea nitrogen (P < 0.001) and creatinine
      levels, and an increase in aspartate aminotransferase and alanine
      aminotransferase (P < 0.05) activities in swine administered sodium chlorate at a
      dose of 500 mg kg-1 body weight per day. The histopathological study revealed
      increased numbers of vacuoles in the convoluted tubules, tubular necrosis and
      degeneration of the renal tubular epithelial cells, depletion of nuclei and
      lobular necrosis of the liver in all pigs treated with sodium chlorate at 500 mg
      kg-1 body weight per day. Thus, 7-day administration of sodium chlorate at 500 mg
      kg-1 body weight per day to pigs affects the liver and kidney tissues as well as
      the haematologic and serum biochemical parameters.

PMID- 22366136
TI  - Effect of lignin on oxidative stress in chickens fed a diet contaminated with
      zearalenone.
AB  - The effect of lignin supplementation to a diet contaminated with zearalenone
      (ZEA) on antioxidant status was studied in female chickens of the ISA BROWN
      laying strain. From the day of hatching to 2 weeks of age, four groups of
      chickens were fed the same uncontaminated control diet. After 14 days, Group 1
      (control) continued to receive the uncontaminated diet, while Group 2 was fed an
      identical diet enriched with 0.5% chemically modified lignin. Simultaneously,
      chickens of Group 3 were switched to a diet contaminated with 7.9 mg/kg ZEA and
      those of Group 4 to an identical contaminated diet supplemented with 0.5% lignin.
      At 6 weeks of age blood and tissue samples were collected. Feeding of a diet
      contaminated with a high level of ZEA resulted in elevated glutathione peroxidase
      (GPx) activity in the duodenal mucosa and kidney tissues, and an increased gamma
      glutamyltransferase (GGT) activity in the plasma, indicative of oxidative stress.
      In the liver tissue, no mycotoxin-induced response in GPx and thioredoxin
      reductase (TrxR) activities occurred, and the malondialdehyde (MDA) level was
      even reduced. Neither the plasma levels of retinol and alpha-tocopherol nor the
      activities of superoxide dismutase in erythrocytes and GPx in blood were affected
      in birds fed the contaminated diet. The only effect of lignin supplemented to the
      contaminated feed was that it prevented the increase of GPx activity in the
      duodenal mucosa as an indicator of oxidative stress.

PMID- 22366137
TI  - Artificial insemination of small ruminants - a review.
AB  - Artificial insemination (AI) can undoubtedly be regarded as the oldest and most
      widely used assisted reproductive technique/technology (ART) applied in livestock
      production and it is one of the most important ARTs. The three cornerstones of
      its application are that it is simple, economical and successful. Artificial
      insemination offers many well-known benefits for producers. Fresh, fresh +
      diluted + chilled and frozen semen can be used for AI in small ruminants. To
      ensure its successful use, the AI technique must be selected on the basis of the
      type of semen planned to be used. This review paper gives a detailed overview of
      semen processing and its effects on semen quality, as well as of the AI
      techniques applied in small ruminants and their success rates.

PMID- 22366138
TI  - Seasonal fertility differences in synchronised dairy cows: ultrasonic, metabolic
      and endocrine findings.
AB  - The aim of this study was to identify relationships among seasonal differences of
      fertility, metabolic parameters and appearance of irregular luteal forms in high
      yielding dairy cows. Holstein-Friesian cows were put on the Provsynch regimen in
      winter (n = 10) and in summer (n = 10). Blood sampling (starting 35 days post
      partum) and rectal ultrasound examinations (starting post insemination) were
      carried out once a week in each examination period. Metabolic [plasma
      nonesterified fatty acid (NEFA) and beta-hydroxybutyrate (BHB) levels, ferric
      reducing ability of plasma (FRAP) and serum beta-carotene] and endocrine
      parameters [plasma thyroxine (T4), triiodothyronine (T3), insulin-like growth
      factor (IGF-I) and insulin levels] were measured. In summer, two cows were
      excluded from the study because of metritis and none of the remaining animals
      became pregnant, but 6 of the 8 cows had irregular luteal forms (ILF) on their
      ovaries. In winter, one cow was excluded because of metritis and 6 of the 9 cows
      became pregnant, while 2 of the 3 open cows had irregular luteal forms. In summer
      the mean plasma NEFA and BHB concentrations were significantly higher, while
      serum carotene and plasma IGF-I concentrations were significantly lower than in
      winter. The high plasma NEFA concentration found in summer seemed to be in
      association with the lower body condition score (BCS) caused by depressed
      appetite. In conclusion, statistical analysis supports the hypothesis that
      increased plasma NEFA and BHB and decreased plasma IGF-I concentrations may
      result in reduced fertility in summer. These changes may be associated with the
      more frequent appearance of ILFs and probably have a negative effect on ovarian
      function and/or oocyte quality.

PMID- 22366139
TI  - Evaluation of the on-line electrical conductivity of milk in mastitic dairy cows.
AB  - Mastitis is a persistent, inflammatory reaction of the udder tissue, which
      entails a decline in potassium, and is also responsible for a higher somatic cell
      count (SCC) and electrical conductivity (EC) of milk. The measurement of EC is an
      indirect, rapid method to detect subclinical mastitis from milk. The aim of this
      study was to analyse the EC of milk throughout the lactation, around the day of
      mastitis detection, and also to estimate its heritability based on data from a
      large-scale dairy farm. Shortly after calving the EC value generally decreases;
      however, it was discovered that from the thirteenth week onwards, substantial
      differences arise between the mastitic and healthy groups of cows. The authors
      observed a significant (P < 0.001) increase in EC before the detection of
      clinical mastitis. This higher value (around 11 mS) persisted for 4 days, then it
      gradually returned to the normal level. The EC of milk from daughters sired by
      different bulls responded differently in case of mastitis. The heritability of EC
      seems to be high (h2 = 0.56). Therefore, the EC trait can be a beneficial
      indicator in detecting mastitis and should be considered in sire selection.

PMID- 22366140
TI  - Genetic diversity analysis of the ORF5 gene in porcine reproductive and
      respiratory syndrome virus samples from South China.
AB  - To understand the genetic diversity of porcine reproductive and respiratory
      syndrome virus (PRRSV) in South China, we collected 231 clinical samples from
      pigs with suspected PRRSV infection in Guangdong between 2007 and 2009. We found
      that 74 of 231 samples were positive by RT-PCR. The PCR products of the ORF5 gene
      of 35 isolates from different farms were sequenced and their DNA sequences were
      compared to 23 other PRRSV isolates in the GenBank. We found that the nucleotide
      similarity among all South China isolates ranged from 87.6% to 100%, and all
      belonged to the North American genotype. Most of them were classified into
      subgenotype I, but the rest mapped to subgenotypes III, V or VI. Those in
      subgenotypes I and III were found to be highly variable in the primary
      neutralising epitope (PNE) with a specific amino acid mutation (F39/L39->I39),
      and a few isolates in subgenotypes I and III isolates also had a mutation at L41
      (L41->S41). PRRSV isolates in subgenotypes III, V and VI had less potential
      glycosylation sites than those in subgenotype I. Our data contribute to the
      understanding of molecular variation of PRRSV in South China.

PMID- 22366141
TI  - Detection of very virulent infectious bursal disease virus from a field outbreak
      in Central India.
AB  - In order to detect infectious bursal disease virus (IBDV), bursal tissue was
      collected from 10 IBD-suspected birds from a 30-day-old, IBDV-vaccinated
      commercial broiler chicken flock of 2000 birds exhibiting clinical signs
      suggestive of infectious bursal disease (IBD). The presence of IBDV was confirmed
      by partial amplification of the VP2 gene by reverse transcription and polymerase
      chain reaction. Isolates were identified as very virulent strains of IBDV
      (vvIBDV) by nucleotide sequence analysis. The comparison of the VP2 nucleotide
      sequences among the isolates revealed the presence of single-nucleotide
      polymorphisms in the VP2 gene of IBDV in the same flock. The comparative analysis
      indicated that these viruses were genetically close to the vvIBDVs previously
      detected in India. Our analysis provided information about the existence of
      vvIBDV in Central India.

PMID- 22366142
TI  - Molecular characterisation of the ORF68 region of equine herpesvirus-1 strains
      isolated from aborted fetuses in Hungary between 1977 and 2008.
AB  - Equine herpesvirus-1 (EHV-1) can be classified into distinct groups by single
      nucleotide polymorphisms (SNPs) in their genomes. Only a few of these can be
      associated with a special attribute of the virus. Differences in the ORF30 region
      can determine the neuropathogenic potential, while by substitutions in the ORF68
      region several strain groups can be made. In previous studies no connection was
      found between the neuropathogenic potential and the SNPs in ORF68, but the
      occurrence of members of distinct groups in different outbreaks can facilitate
      epidemiological investigations because the geographical distribution of a
      particular group is very often specific. The present study aimed at the molecular
      examination and grouping of 35 EHV-1 strains isolated from aborted equine fetuses
      in Hungary between 1977 and 2008. Genotyping was based on the comparison of
      nucleotide sequences of a polymorphic segment located in the ORF68 region, which
      had previously been found to be a useful tool for classification. After
      sequencing this region, the Hungarian EHV-1 isolates could be classified into
      seven groups. Only 23 of the 35 isolates belonged to the formerly described
      groups, while the SNPs of 12 isolates diverged, and four new groups could be set
      up. In addition, phylogenetic analysis was performed to compare the ORF68
      sequences of the Hungarian strains with the sequences of isolates from Europe,
      America and Australia. The number of newly formed groups suggests that the
      further analysis of unknown EHV-1 isolates would involve the emergence of
      extended numbers of new groups, which can impair the usability of this grouping
      method.

PMID- 22366143
TI  - Glucocorticoids reduce alveolar and trabecular bone in mice.
AB  - Glucocorticoid (GC) treatment is the main cause of secondary osteoporosis. There
      are some controversies about the relationships between alveolar bone loss and
      bone loss at the appendicular and axial skeleton. OBJECTIVE: To assess, in
      parallel, the effects of GCs on alveolar bone and on the tibia in a mice model.
      METHODS: Five-month-old male Swiss-Webster mice were randomized into two groups.
      Pellets releasing 5 mg/kg/day of prednisolone or control pellets were
      subcutaneously implanted for 28 days. After euthanasia, the right tibia and the
      right hemimandible of each mouse were analyzed by histomorphometry and
      microcomputed tomography. Alveolar bone consists of a thin slab between the
      incisor and the molar roots connected with the alveolar processes. A 2D-frontal
      section was done through the pulp chamber of the first molar and was used to
      measure the thickness of the alveolar bone slab. A 2D-sagittal section was done
      through the pulp chamber of the three molars and was used to measure bone volume
      in the alveolar processes. RESULTS: At day 28, thickness and bone volume of
      alveolar bone were significantly decreased in the GC group (P<0.05). At the
      tibia, GCs decreased bone formation with a reduced mineral apposition rate and
      bone formation rate and a significant decrease in BV/TV and Tb.Th (P<0.05).
      CONCLUSION: Although the amount of alveolar bone is very low in the mouse, this
      study shows that GCs can induce an alveolar bone loss in long-term treated
      animals.

PMID- 22366144
TI  - Parry-Romberg syndrome in an 11-year-old female with neurological manifestations
      without brain imaging abnormalities.

PMID- 22366145
TI  - Citrullination under physiological and pathological conditions.
AB  - Citrullination, one of the enzymatic posttranslational modifications has become a
      hot topic of recent research as it is involved in various physiological and
      pathological processes. Antibodies against citrullinated proteins called anti
      citrullinated protein antibodies, are the hallmark (diagnostic and prognostic
      factors) of rheumatoid arthritis, and are specific for the disease.
      Citrullination has an important role in the normal function of the immune system,
      skin keratinization, the insulation of neurons and the plasticity of the central
      nervous system including its essential role in gene regulation. Abnormal
      citrullination has been proposed to play a role in multiple sclerosis and
      Alzheimer's disease, and recent research has drawn attention to its implication
      in tumorigenesis. Still, it is unclear whether citrullination is the cause or the
      consequence of these pathological alterations. Here, we discuss crucial aspects
      of citrullination during both physiological and pathological conditions.

PMID- 22366146
TI  - Therapeutic perspectives on uricases for gout.
AB  - Available recombinant uricases (rasburicase, pegloticase) are potent
      hypouricaemic agents for tophaceous gout, but their long-term use is in question.
      We have performed a literature review on uricases, using Scirus, PubMed, Science
      Direct, and several other search engines. We have also consulted the records of
      drug regulatory authorities and patents on uricases. Rasburicase (Fasturtec((r)))
      was approved in Europe for tumour lysis syndrome induced by chemotherapy, in a
      single daily infusion dose for a maximum of 7 days. A retrospective study (n=10)
      conducted in patients with gout and three clinical cases have shown that
      infusions spaced over time, over several months, ensure the control of serum uric
      acid and help to eliminate or significantly reduce the size of tophi. However,
      repeated gout attacks (despite colchicine) and hypersensitivity reactions
      (despite corticosteroids) have dampened enthusiasm for its use in gout.
      Pegloticase was recently approved by the Food and Drug Administration (FDA) for
      patients with chronic gout, refractory or intolerant to conventional
      hypouricaemic therapy. A 6 month study versus placebo showed that pegloticase
      (infused at 8 mg every 2 weeks), induced a significant decrease in plasma uric
      acid in about 40% of patients (associated with a tendency for tophi dissolution).
      However, the remaining patients were non-responders, which correlated with the
      formation of pegloticase antibodies and infusion reactions. Research efforts are
      needed to develop less immunogenic uricases. In conclusion, some uricases could
      have an important role in the treatment of gout, for instance as a first-line
      treatment and over a short period of several months in patients with severe and
      tophaceous gout to allow rapid tophi dissolution.

PMID- 22366147
TI  - Two cases of ankylosing spondylitis and Wilson's disease in the same patient.
      Only a fortuitous association?

PMID- 22366148
TI  - Ivory vertebra and systemic mastocytosis.
AB  - The ivory vertebra sign seen on a standard radiograph of the spine should prompt
      investigations for a cause, which is most likely to be a bone metastasis, a
      lymphoma, or Paget's disease of bone. A diagnosis of idiopathic ivory vertebra
      can be given if no cause is identified. We report an unusual case of ivory
      vertebra sign that was due to systemic mastocytosis and improved with specific
      treatment. Although osteoporosis is the most common bone abnormality in systemic
      mastocytosis, an isolated sclerotic or lytic lesion may be found. The ivory
      vertebra sign should not be considered idiopathic until tests are done for
      mastocytosis, particularly given the availability of effective treatments.

PMID- 22366149
TI  - Multilevel spinal stenosis at cervical, thoracic and lumbar spine: a clinical
      report.

PMID- 22366150
TI  - Cost-effectiveness of osteoporosis treatments in postmenopausal women using
      FRAXTM thresholds for decision.
AB  - PURPOSE: FRAXTM is a fracture prediction algorithm to determine a patient's
      absolute fracture risk. There is a growing consensus that osteoporosis treatment
      should be based on individual 10-year fracture probability, as calculated in the
      FRAXTM algorithm, rather than on T-scores alone. OBJECTIVE: Our objective was to
      evaluate the cost-effectiveness of five years of branded alendronate therapy in
      postmenopausal French women with a known FRAXTM score. METHOD: A Markov cohort
      state transition model using FRAXTM values and whenever possible population
      specific data and probabilities. We estimated the incremental cost-effectiveness
      ratio (ICER) of alendronate versus no treatment in postmenopausal women with
      FRAXTM ranging from 10 to 3%. OUTCOMES: Number of women to treat (NNT) for
      preventing hip fracture, costs, quality-adjusted life-years, incremental cost
      effectiveness ratios. RESULTS: The incremental cost-effectiveness ratios (ICER)
      compared to no treatment at age 70 ranged from ?104,183 to ?413,473 per QALY when
      FRAXTM decreased from 10 to 3%. The NNTs for preventing one hip fracture ranged
      from 97 to 388 according to age (50-80 years) and FRAXTM. Sensitivity analyses
      showed that the main determinants of cost-effectiveness were adherence to therapy
      and cost of treatment. CONCLUSION: Using French costs of branded drug and current
      estimates of treatment efficacy, alendronate therapy for 70-year-old women with
      10-year probability of hip fracture of 10% just meets the accepted cost
      effectiveness threshold. Improving treatment adherence and/or decreasing
      treatment cost lowers the ICER. The model however underestimates the potential
      benefit by excluding other fractures.

PMID- 22366151
TI  - Evolution of surgical treatment paradigms for advanced-stage ovarian cancer:
      redefining 'optimal' residual disease.
AB  - Over the past 40 years, the survival of patients with advanced ovarian cancer has
      greatly improved due to the introduction of combination chemotherapy with
      platinum and paclitaxel as standard front-line treatment and the progressive
      incorporation of increasing degrees of maximal cytoreductive surgery. The
      designation of "optimal" surgical cytoreduction has evolved from residual disease
      <= 1 cm to no gross residual disease. There is a growing body of evidence that
      patients with no gross residual disease have better survival than those with
      optimal but visible residual disease. In order to achieve this, more radical
      cytoreductive procedures such as radical pelvic resection and extensive upper
      abdominal procedures are increasingly performed. However, some investigators
      still suggest that tumor biology is a major determinant in survival and that
      optimal surgery cannot fully compensate for tumor biology. The aim of this review
      is to outline the theoretical rationale and historical evolution of primary
      cytoreductive surgery, to re-evaluate the preferred surgical objective and
      procedures commonly required to achieve optimal cytoreduction in the
      platinum/taxane era based on contemporary evidence, and to redefine the concept
      of "optimal" residual disease within the context of future surgical developments
      and analysis of treatment outcomes.

PMID- 22366152
TI  - Second Biennial Meeting of Asian Society of Gynecologic Oncology (ASGO): a
      turning point from good old days to a better future.

PMID- 22366153
TI  - Activity-related dyspnea is not modified by psychological status in people with
      COPD, interstitial lung disease or obesity.
AB  - Sensory (physiological) and affective (psychological) dimensions of dyspnea have
      been described but the usefulness of measuring psychological status in addition
      to ventilatory capacity (spirometry, lung volumes) in the assessment of
      exertional dyspnea remains controversial. We hypothesized that activity-related
      dyspnea would not be modified by psychological status. Principal component
      analysis (PCA) was used to reduce the number of parameters (psychological or
      functional) to fewer independent dimensions in 328 patients with altered
      ventilatory capacity: severe obesity (BMI >= 35, n = 122), COPD (n = 128) or
      interstitial lung disease (n = 78). PCA demonstrated that psychological status
      (Hospital Anxiety-Depression, Fatigue Impact scales) and dyspnea (Medical
      Research Council [MRC] scale) were independent dimensions. Ventilatory capacity
      was described by three main dimensions by PCA related to airways, volumes, and
      their combination (specific airway resistance, FEV(1)/FVC), which were weakly
      correlated with dyspnea. In conclusion, in patients with COPD, interstitial lung
      disease or severe obesity, psychological status does not modify activity-related
      dyspnea rating as evaluated by the MRC scale.

PMID- 22366154
TI  - Gas exchange measurements within a magnetic environment: validation of a new
      system.
AB  - Although simultaneous measurements of pulmonary oxygen uptake (VO2) and
      Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is attractive to
      investigate muscular metabolism during exercise, the superconducting magnet
      requires the design of specific gas exchange analyser (GEA). Thus, this study
      aimed to assess the validity of a commercial GEA system (ZAN600) compatible with
      (31)P MRS measurements. Using nonmagnetic pneumotachograph and prolonged sampling
      line (from 2m, control condition, to 6.5m) did not alter the proper
      synchronisation between flow and gas concentration signals. Also, end-expiratory
      fraction of O2 (FETO2) and CO(2) (FETCO2), and finally the values of steady-state
      ventilation (V(E)), carbon dioxide production (VCO2) and VO2 kinetics during
      moderate knee-extension exercise were not significantly different between 2m and
      6.5m conditions and between 6.5m condition inside and outside the magnet. These
      results showed that a prolonged sampling line used inside the superconducting
      magnet did not affect the accuracy of VO2 measurements of a commercial GEA
      system; the latter appears suitable for simultaneous measurements of VO2 and
      (31)P MRS.

PMID- 22366155
TI  - Acute phase response, inflammation and metabolic syndrome biomarkers of Libby
      asbestos exposure.
AB  - Identification of biomarkers assists in the diagnosis of disease and the
      assessment of health risks from environmental exposures. We hypothesized that
      rats exposed to Libby amphibole (LA) would present with a unique serum proteomic
      profile which could help elucidate epidemiologically-relevant biomarkers. In four
      experiments spanning varied protocols and temporality, healthy (Wistar Kyoto,
      WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously
      hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with
      saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic
      syndrome (MetS), and the acute phase response (APR) were analyzed. All rat
      strains exhibited acute increases in alpha-2-macroglobulin, and alpha1-acid
      glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH
      and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age
      related changes were apparent in MetS biomarkers, no LA effects were evident. The
      cancer marker mesothelin was increased only slightly at 1 month in WKY in one of
      the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4
      weeks after 4 weekly LA instillations indicated no oxidative protein
      modifications, however APR proteins were significantly increased. Those included
      serine protease inhibitor, apolipoprotein E, alpha-2-HS-glycoprotein, t-kininogen
      1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1
      day after last LA exposure. All changes were reversible after a short recovery
      regardless of the acute or long-term exposures. Thus, LA exposure induces an APR
      and systemic inflammatory biomarkers that could have implications in systemic and
      pulmonary disease in individuals exposed to LA.

PMID- 22366156
TI  - [Drugs news: special neonatalogy].

PMID- 22366157
TI  - Food selection and taste changes in humans after Roux-en-Y gastric bypass
      surgery: a direct-measures approach.
AB  - It has been suggested that the weight loss seen in individuals who receive Roux
      en-Y gastric bypass surgery may be due, at least in part, to changes in patient
      food selection, and that this change may stem from effects of the operation on
      the sense of taste. In this review, we evaluate the literature examining
      postoperative changes in food intake and food choice. While some evidence
      suggests that gastric bypass leads to altered food selection and taste
      perceptions, a clear picture regarding these changes remains to be elucidated and
      is blurred by inconsistencies, which may be rooted in the diverse subject pools
      within and between studies as well as in the indirect measures used to assess
      ingestive behavior. We argue that complementing current assessment tools with
      more direct measures of intake, food selection, and taste-related behavior might
      help provide some clarity and also facilitate translation between findings from
      animal models, in which similar measures are available, and clinical research.

PMID- 22366158
TI  - The mismatch hypothesis of psychiatric disease.

PMID- 22366159
TI  - Sexually active bucks are able to stimulate three successive groups of females
      per day with a 4-hour period of contact.
AB  - Bucks rendered sexually active by a photoperiod treatment of long days can induce
      fertile ovulation in a group of goats with only 4 h of contact daily with a
      male:female ratio of 1:10. Here we tested whether such bucks could induce fertile
      ovulations when stimulating successively three different groups of anovulatory
      goats when interacting 4 h per day during 15 consecutive days. Control males
      (n=3) were introduced in the control group (n=25) of does at 8:00 h and were
      removed at 12:00 h. Experimental males (n=3) were in contact with the
      experimental groups of does: from 8:00 h to 12:00 h with a first group (n=27),
      from 12:00 h to 16:00 h with a second group (n=26) and with a third one (n=27)
      from 16:00 h to 20:00 h. Bucks were then placed until next day in another pen.
      Both in the control and the experimental groups, more than 85% of females
      ovulated, and the proportions did not differ between the control and experimental
      groups (P>=0.67) or between the three experimental groups (P>=0.67). Moreover,
      the ovulation rate did not differ significantly between the control and the
      experimental females nor between the three experimental groups. Bucks were able
      to fertilize more than 72% of does independently of the number of females they
      were exposed to (P>=0.17). Finally, more than 58% of females kidded and fertility
      did not differ between the control and experimental groups (P=1) nor among
      experimental groups (P>=0.77). We conclude that sexually active bucks are able to
      induce fertile ovulation in three successive groups of anovulatory goats even
      when the period of contact between sexes is reduced to 4 h per day.

PMID- 22366160
TI  - Sex differences in HPA axis activity in response to a meal.
AB  - BACKGROUND: Sex may influence the relationship between HPA axis functioning and
      obesity. This has been suggested to be due to sex-specific differences in body
      composition, body fat distribution and psychological variables. Age and the use
      of oral contraceptives may also influence the relationship between HPA axis
      functioning and obesity. OBJECTIVE: To systematically investigate whether body
      composition, body fat distribution, psychological variables, age, or possible
      oral contraceptive use contribute to sex differences in HPA axis activity in
      response to a meal. METHODS: Subjects were men (n=19) and women (n=19) between 18
      and 51 years old with BMI between 20.3 and 33.2 kg/m(2). HPA axis activity was
      measured by salivary free cortisol levels before consuming a meal, and at 45, 75
      and 125 min postprandial on four repeated test days. Anthropometric and body
      composition measurements were performed. Questionnaires were used to assess
      cognitive eating behavior and trait anxiety level. RESULTS: No differences
      between the test days in postprandial cortisol responses appeared. Responses were
      significantly higher in men compared with women (p<.05). No significant
      correlations were found between cortisol concentrations and sex-specific body
      composition or body fat distribution. Psychological variables did not contribute
      to differences in cortisol responses after a meal between men and women. In
      women, baseline cortisol concentrations correlated inversely with age (p=.024).
      CONCLUSION: Higher HPA axis activity following a meal in men vs. women remained
      irrespective of sex-specific differences in body composition, body fat
      distribution, psychological variables, or in age. In women baseline cortisol
      concentrations were age-dependent.

PMID- 22366162
TI  - STAY-GREEN and chlorophyll catabolic enzymes interact at light-harvesting complex
      II for chlorophyll detoxification during leaf senescence in Arabidopsis.
AB  - During leaf senescence, plants degrade chlorophyll to colorless linear
      tetrapyrroles that are stored in the vacuole of senescing cells. The early steps
      of chlorophyll breakdown occur in plastids. To date, five chlorophyll catabolic
      enzymes (CCEs), NONYELLOW COLORING1 (NYC1), NYC1-LIKE, pheophytinase,
      pheophorbide a oxygenase (PAO), and red chlorophyll catabolite reductase, have
      been identified; these enzymes catalyze the stepwise degradation of chlorophyll
      to a fluorescent intermediate, pFCC, which is then exported from the plastid. In
      addition, STAY-GREEN (SGR), Mendel's green cotyledon gene encoding a chloroplast
      protein, is required for the initiation of chlorophyll breakdown in plastids.
      Senescence-induced SGR binds to light-harvesting complex II (LHCII), but its
      exact role remains elusive. Here, we show that all five CCEs also specifically
      interact with LHCII. In addition, SGR and CCEs interact directly or indirectly
      with each other at LHCII, and SGR is essential for recruiting CCEs in senescing
      chloroplasts. PAO, which had been attributed to the inner envelope, is found to
      localize in the thylakoid membrane. These data indicate a predominant role for
      the SGR-CCE-LHCII protein interaction in the breakdown of LHCII-located
      chlorophyll, likely to allow metabolic channeling of phototoxic chlorophyll
      breakdown intermediates upstream of nontoxic pFCC.

PMID- 22366161
TI  - New technologies for 21st century plant science.
AB  - Plants are one of the most fascinating and important groups of organisms living
      on Earth. They serve as the conduit of energy into the biosphere, provide food,
      and shape our environment. If we want to make headway in understanding how these
      essential organisms function and build the foundation for a more sustainable
      future, then we need to apply the most advanced technologies available to the
      study of plant life. In 2009, a committee of the National Academy highlighted the
      "understanding of plant growth" as one of the big challenges for society and part
      of a new era which they termed "new biology." The aim of this article is to
      identify how new technologies can and will transform plant science to address the
      challenges of new biology. We assess where we stand today regarding current
      technologies, with an emphasis on molecular and imaging technologies, and we try
      to address questions about where we may go in the future and whether we can get
      an idea of what is at and beyond the horizon.

PMID- 22366164
TI  - Prognostic value of combining high sensitive troponin T and N-terminal pro B-type
      natriuretic peptide in chest pain patients with no persistent ST-elevation.
AB  - The aim was to examine whether high sensitive troponin T (Hs-TnT) is better than
      conventional troponins to risk stratify chest pain patients, in particular when
      applying early serial measurements or combining with natriuretic peptides.
      Samples were obtained on admission and after 2 h in 231 chest pain patients who
      were followed for a median time of 22 months. Troponin levels were determined by
      Hs-TnT, conventional TnT (Roche Diagnostics) and troponin I (Beckman Coulter)
      assays. N-terminal pro B-type natriuretic peptide (NT-proBNP) was determined by
      the assay from Roche Diagnostics. The combined endpoint was death, MI or heart
      failure. When predefined decision limits were used, Hs-TnT (14 ng/L), TnT (0.04
      MUg/L), and TnI (0.06 MUg/L) identified 63%, 46%, and 52% of the patients with
      positive troponin. In those with negative TnT, Hs-TnT identified 36 patients of
      whom 19% had subsequent events. In those with negative TnI, Hs-TnT identified 26
      patients of whom 23% had subsequent events. After adjusting for differences in
      baseline characteristics, both Hs-TnT and NT-proBNP were independently associated
      with short-term (3 months) risk of combined endpoint and long-term risk of death
      or MI. By combining Hs-TnT and NT-proBNP patients could be divided into low-,
      intermediate- and high-risk groups.

PMID- 22366163
TI  - Sulfatases are determinants of alveolar formation.
AB  - Alveolar formation or alveolarization is orchestrated by a finely regulated and
      complex interaction between growth factors and extracellular matrix proteins. The
      lung parenchyma contains various extracellular matrix proteins including
      proteoglycans, which are composed of glycosaminoglycans (GAGs) linked to a
      protein core. Although GAGs are known to regulate growth factor distribution and
      activity according to their degree of sulfation the role of sulfated GAG in the
      respiratory system is not well understood. The degree of sulfation of GAGs is
      regulated in part, by sulfatases that remove sulfate groups. In vertebrates, the
      enzyme Sulfatase-Modifying Factor 1 (Sumf1) activates all sulfatases. Here we
      utilized mice lacking Sumf1(-/-) to study the importance of proteoglycan
      desulfation in lung development. The Sumf1(-/-) mice have normal lungs up until
      the onset of alveolarization at post-natal day 5 (P5). We detected increased
      deposition of sulfated GAG throughout the lung parenchyma and a decrease in
      alveolar septa formation. Moreover, stereological analysis showed that the
      alveolar volume is 20% larger in Sumf1(-/-) as compared to wild type (WT) mice at
      P10 and P30. Additionally, pulmonary function test was consistent with increased
      alveolar volume. Genetic experiments demonstrate that in Sumf1(-/-) mice arrest
      of alveolarization is independent of fibroblast growth factor signaling. In turn,
      the Sumf1(-/-) mice have increased transforming growth factor beta (TGFbeta)
      signaling and in vivo injection of TGFbeta neutralizing antibody leads to
      normalization of alveolarization. Thus, absence of sulfatase activity increases
      sulfated GAG deposition in the lungs causing deregulation of TGFbeta signaling
      and arrest of alveolarization.

PMID- 22366165
TI  - CXCL10: a candidate biomarker in transplantation.
AB  - Interferon (IFN) gamma-induced protein 10 kDa (IP-10) or C-X-C motif chemokine 10
      (CXCL10) is a small cytokine belonging to the CXC chemokine family. This family
      of signaling molecules is known to control several biological functions and to
      also play pivotal roles in disease initiation and progression. By binding to its
      specific cognate receptor CXCR3, CXCL10 critically regulates chemotaxis during
      several immune-inflammatory processes. In particular, this chemokine controls
      chemotaxis during the inflammatory response resulting from allograft rejection
      after transplantation. Interestingly, a strong association has been described
      between CXCL10 production, immune response and the fate of the graft following
      allotransplantation. Enhanced CXCL10 production has been observed in recipients
      of transplants of different organs. This enhanced production likely comes from
      either the graft or the immune cells and is correlated with an increase in the
      concentration of circulating CXCL10. Because CXCL10 can be easily measured in the
      serum and plasma from a patient, the detection and quantitation of circulating
      CXCL10 could be used to reveal a transplant recipient's immune status. The
      purpose of this review is to examine the critical role of CXCL10 in the
      pathogenesis of allograft rejection following organ transplantation. This
      important role highlights the potential utilization of CXCL10 not only as a
      therapeutic target but also as a biomarker to predict the severity of rejection,
      to monitor the inflammatory status of organ recipients and, hopefully, to fine
      tune patient therapy in transplantation.

PMID- 22366166
TI  - Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis
      of invasive aspergillosis in non-neutropenic patients.
AB  - BACKGROUND: Invasive aspergillosis (IA) is an important cause of mortality in
      critically ill patients, but the diagnosis is difficult as clinical and
      radiological signs are neither sensitive nor specific. Serum galactomannan (GM)
      is a useful marker for IA, but exhibits low sensitivity in non-neutropenic
      patients. In our previous work, strong antibody reactivity to thioredoxin
      reductase of Aspergillus fumigatus was found in non-neutropenic IA patients.
      METHODS AND RESULTS: Using recombinant thioredoxin reductase GliT (TR), an
      antigenic protein secreted by A. fumigatus, as the coating antigen, an enzyme
      linked immunosorbent assay (ELISA) for detecting anti-TR antibodies was
      developed. The antibody response to TR in IA animal models and 42 non-neutropenic
      patients with culture- and/or histology-documented IA was investigated. The
      results showed that anti-TR antibody was detectable in rabbit serum 7-9 days
      after exposure to the fungus. The sensitivity and specificity of the anti-TR
      antibody assay in patients were 80.9% and 96%, respectively, while the
      sensitivity of GM in this group of patients was only 52.3%. The specificity of
      the assay was confirmed by testing the sera from patients infected with other
      pathogenic fungal species and bacteria.

PMID- 22366167
TI  - Discrimination makes me sick! An examination of the discrimination-health
      relationship.
AB  - The attitudes of the general British population towards Muslims changed post
      2001, and this change led to a significant increase in Anti-Muslim
      discrimination. We use this exogenous attitude change to estimate the causal
      impact of increased discrimination on a range of objective and subjective health
      outcomes. The difference-in-differences estimates indicate that discrimination
      worsens blood pressure, cholesterol, BMI and self-assessed general health. Thus,
      discrimination is a potentially important determinant of the large racial and
      ethnic health gaps observed in many countries. We also investigate the pathways
      through which discrimination impacts upon health, and find that discrimination
      has a negative effect on employment, perceived social support, and health
      producing behaviours. Crucially, our results hold for different control groups
      and model specifications.

PMID- 22366168
TI  - Evidence for a relationship between mitochondrial Complex I activity and
      mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: effects of
      mitochondrial antioxidants.
AB  - The medical use of nitroglycerin (GTN) is limited by patient tolerance. The
      present study evaluated the role of mitochondrial Complex I in GTN
      biotransformation and the therapeutic effect of mitochondrial antioxidants. The
      development of GTN tolerance (in rat and human vessels) produced a decrease in
      mitochondrial O(2) consumption. Co-incubation with the mitochondria-targeted
      antioxidant mitoquinone (MQ, 10(-6)mol/L) or with glutathione ester (GEE, 10(
      4)mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial
      respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of
      GTN depended on the mitochondria being functionally active, particularly
      mitochondrial Complex I. Tolerance induced mitochondrial ROS production and
      oxidative stress, though these effects were not detected in HUVECrho(0) cells or
      Complex I mutant cells. Experiments performed to evaluate Complex I-dependent
      respiration demonstrated that its inhibition by GTN was prevented by the
      antioxidants in control samples. These results point to a key role for
      mitochondrial Complex I in the adequate functioning of ALDH-2. In addition, we
      have identified mitochondrial Complex I as one of the targets at which the
      initial oxidative stress responsible for GTN tolerance takes place. Our data also
      suggest a role for mitochondrial-antioxidants as therapeutic tools in the control
      of the tolerance that accompanies chronic nitrate use.

PMID- 22366169
TI  - The single NqrB and NqrC subunits in the Na(+)-translocating NADH: quinone
      oxidoreductase (Na(+)-NQR) from Vibrio cholerae each carry one covalently
      attached FMN.
AB  - The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is the prototype
      of a novel class of flavoproteins carrying a riboflavin phosphate bound to serine
      or threonine by a phosphodiester bond to the ribityl side chain. This membrane
      bound, respiratory complex also contains one non-covalently bound FAD, one non
      covalently bound riboflavin, ubiquinone-8 and a [2Fe-2S] cluster. Here, we report
      the quantitative analysis of the full set of flavin cofactors in the Na(+)-NQR
      and characterize the mode of linkage of the riboflavin phosphate to the membrane
      bound NqrB and NqrC subunits. Release of the flavin by beta-elimination and
      analysis of the cofactor demonstrates that the phosphate group is attached at the
      5'-position of the ribityl as in authentic FMN and that the Na(+)-NQR contains
      approximately 1.7mol covalently bound FMN per mol non-covalently bound FAD.
      Therefore, each of the single NqrB and NqrC subunits in the Na(+)-NQR carries a
      single FMN. Elimination of the phosphodiester bond yields a dehydro-2
      aminobutyrate residue, which is modified with beta-mercaptoethanol by Michael
      addition. Proteolytic digestion followed by mass determination of peptide
      fragments reveals exclusive modification of threonine residues, which carry FMN
      in the native enzyme. The described reactions allow quantification and
      localization of the covalently attached FMNs in the Na(+)-NQR and in related
      proteins belonging to the Rhodobacter nitrogen fixation (RNF) family of enzymes.
      This article is part of a Special Issue entitled: 17th European Bioenergetics
      Conference (EBEC 2012).

PMID- 22366171
TI  - Comparison of dual- and triple-freeze protocols for pulmonary cryoablation in a
      Tibet pig model.
AB  - The purpose of this study was to compare a dual-freeze protocol with a triple
      freeze protocol for pulmonary cryoablation in a porcine lung model. Five dual-
      (10-5-10-5) and five triple-freeze (5-5-5-5-10-5) cryoablations were performed on
      an exposed operation field in normal porcine lung. Changes in the temperature of
      the cryoprobes and the diameter of the iceballs were measured during the ablation
      and pathologic changes in the cryozones (zones of tissue destruction) were
      reviewed 7 days after the procedure. The diameter of the iceball surface differed
      between the two protocols. Pathologically, the triple-freeze protocol was
      associated with a longer complete necrosis zone than the dual-freeze protocol,
      though the two protocols produced cryolesions and cryozones of similar length,
      and in both cases there were five areas of tissue destruction. With the same
      duration of freezing (20 min), the triple-freeze protocol may be better for
      pulmonary cryoablation than the dual-freeze protocol.

PMID- 22366170
TI  - Breast density, body mass index, and risk of tumor marker-defined subtypes of
      breast cancer.
AB  - PURPOSE: Breast density and body mass index (BMI) are correlated attributes and
      are both potentially modifiable risk factors for breast cancer. However,
      relationships between these factors and risk of molecularly-defined subtypes of
      breast cancer have not been established. METHODS: We used breast density and BMI
      data collected by the Breast Cancer Surveillance Consortium from 1,054,466 women
      ages 40 to 84 years receiving mammography, including 13,797 women subsequently
      diagnosed with breast cancer. Cases were classified into three groups on the
      basis of expression of the estrogen receptor (ER), progesterone receptor (PR),
      and HER2:1) ER-positive (ER+, n = 10,026), 2) HER2-expressing (ER-negative/PR
      negative/HER2-positive, n = 308), or triple-negative (ER-negative/PR
      negative/HER2-negative, n = 705). Using Cox regression, we evaluated subtype
      specific associations with breast density and BMI. RESULTS: Breast density was
      similarly positively associated with risk of all subtypes, especially among women
      ages 40 to 64 years. BMI was positively associated with risks of ER+ and triple
      negative breast cancer in women ages 50 to 84 who were not users of hormone
      therapy. CONCLUSIONS: Breast density is positively associated with breast cancer
      risk, regardless of disease subtype. Associations with BMI appear to vary more by
      breast cancer subtype. Additional studies are needed to confirm and further
      characterize risk factors for HER2-expressing and triple-negative breast cancer.

PMID- 22366172
TI  - Culturing with trehalose produces viable endothelial cells after
      cryopreservation.
AB  - Dimethylsulfoxide, the most commonly employed cryoprotectant for cells, has well
      documented cytotoxic effects in patients. Among the compounds available that may
      provide protection to cells and tissues during preservation with less
      cytotoxicity is trehalose. Some animals, such as brine shrimp and tardigrades,
      accumulate trehalose during periods of extreme environmental stress. In this
      study, experiments were performed to evaluate the effects of culturing a bovine
      endothelial cell line (ATCC #CCL-209) in the presence of trehalose prior to
      preservation by freezing. A number of factors were shown to contribute to cell
      retention of metabolic activity and proliferative potential including cell
      culture time with trehalose and the solution conditions during cryopreservation.
      Using an optimized protocol consisting of 24 h of cell culture with 0.2 M
      trehalose followed by cryopreservation with 0.2-0.4 M trehalose in sodium
      bicarbonate buffered Eagles minimum essential medium at pH 7.4 resulted in 87+/
      4% post-preservation cell metabolic activity expressed as relative fluorescence
      based upon reduction of resazurin to resorufin. This new method provides an
      alternative preservation strategy to the more classical preservation methods
      employing dimethylsulfoxide available for cells and tissues.

PMID- 22366173
TI  - 17beta-Estradiol stimulates the translocation of endogenous estrogen receptor
      alpha at the plasma membrane of normal anterior pituitary cells.
AB  - In the present work we aimed at identifying ERalpha in the plasma membrane of
      normal anterior pituitary cells and investigated if 17beta-estradiol was able to
      induce their subcellular redistribution. Our results show that about 8% of
      anterior pituitary cells expressed ERalpha in the plasma membrane, with the
      geometrical mean fluorescence intensity being increased after steroid hormone
      treatment. 17beta-Estradiol and the selective ERalpha agonist PPT induced an
      increase of ERalpha expression in the plasma membrane and activated the
      PKCalpha/ERK 1/2 pathway in a time-course not compatible with genomic actions,
      thus supporting the notion of membrane-initiated effects. These findings suggest
      that 17beta-estradiol stimulates the translocation of endogenous ERalpha to the
      plasma membrane, consequently modulating this ER pool and leading to cellular
      biological effects in normal anterior pituitary gland.

PMID- 22366174
TI  - Time-resolved fluorescence study during denaturation and renaturation of curcumin
      myoglobin complex.
AB  - Curcumin influences the transition point, the concentration of denaturant
      required to effect 50% of the total change, of myoglobin denaturation. Curcumin
      enhances absorbance of myoglobin at 280 nm with a binding constant K=3.0*10(4) M(
      1) whereas fluorescence of curcumin is quenched by myoglobin with a Stern-Volmer
      association constant of 2.5*10(5) M(-1). Unfolding process of myoglobin-curcumin
      induces a recovery in fluorescence lifetime loss. The gain in time-resolved
      fluorescence lifetime during unfolding has been again lost during refolding of
      curcumin-myoglobin complex by dilution process suggesting partial reversibility
      of unfolding process for both myoglobin and curcumin-myoglobin complex.

PMID- 22366175
TI  - The blood concentration and organ distribution of haloperidol at therapeutic and
      toxic doses in severe fatty liver disease.
AB  - The aim of this study was to investigate the difference between the
      pharmacokinetics of haloperidol in normal rats and in rats with fatty liver
      disease. A therapeutic dosage (0.1 mg/kg) and a toxic dose (15 mg/kg) of
      haloperidol were administrated to normal 9-week-old male rats or those with
      severe fatty liver disease, and the blood concentration of haloperidol was
      determined 15 min, 1, 2, and 3 h following haloperidol administration. The
      concentration of haloperidol in the organs was determined 1, 2, and 3 h after the
      haloperidol administration. Additionally, the volume of the portal vein blood
      flow was measured 3 h after haloperidol administration. When given at the
      therapeutic dosage, the concentrations of haloperidol in both the blood and
      organs of the rats with fatty liver disease were significantly higher than those
      in the normal rats. However, when given at the toxic level, the blood and organ
      haloperidol concentrations 1 h after administration tended to be lower in the
      rats with fatty liver disease than those in the normal rats; these lower
      haloperidol levels returned to be the levels in the normal rats 3 h after the
      administration of haloperidol. The volume of the portal vein blood flow
      significantly increased following the toxic haloperidol dose as compared with the
      volume pre-administration and following the therapeutic haloperidol dose in the
      normal rats. However, the volume did not change after the toxic or the
      therapeutic dose of haloperidol compared with pre-administration in rats with
      severe fatty liver disease, although it was significantly higher than in the
      normal rats. The pathway for haloperidol metabolism might have been saturated
      before the administration of haloperidol in rats with fatty liver disease; thus,
      it is possible that the blood concentration of haloperidol tends to be much
      higher in individuals with severe fatty liver disease than in those with normal
      livers in an inverse proportion to the dosage of haloperidol.

PMID- 22366176
TI  - Postmortem measurement of C-reactive protein and interpretation of results in
      ketoacidosis.
AB  - C-reactive protein (CRP) is a widely used acute phase protein that reacts to
      various tissue-destroying stimuli. Its forensic applications have been
      established in prior studies. We show that CRP can be successfully measured even
      after a long postmortem period, up to 18 days, which has not previously been
      reported. Information on elevated CRP levels can be very valuable for the
      forensic pathologist in autopsy cases with scarce findings. The interpretation of
      results can be very challenging, as the elevation can originate from many
      different reasons, and due to the biochemical changes in cadavers. One less
      studied possible reason for elevated CRP is ketoacidosis. Here, we present a
      study on the effect of both alcoholic and diabetic ketoacidosis on blood CRP
      elevation in forensic autopsy material. Our results imply that ketoacidosis
      itself can cause a rise in CRP without other underlying causes, such as infection
      or trauma. However, more comprehensive studies are required to confirm the
      relationship between ketoacidosis and CRP level elevation.

PMID- 22366177
TI  - Many patients continue using proton pump inhibitors after negative results from
      tests for reflux disease.
AB  - BACKGROUND & AIMS: Ambulatory reflux testing is used to evaluate symptoms of
      gastroesophageal reflux disease (GERD) refractory to protein pump inhibitors
      (PPIs). We investigated the prevalence of PPI use in patients with negative
      results from Bravo pH or multichannel intraluminal impedance-pH (MII-pH) tests
      and factors that might predict the use of PPIs. METHODS: We analyzed data from
      patients who had undergone Bravo pH monitoring or MII-pH testing at Northwestern
      University, without evidence of reflux disease. Demographics, endoscopy findings,
      pathology results, and provider recommendations were obtained via chart review.
      Eligible patients (n = 90) were contacted by telephone, and a cross-sectional
      survey was administered with questions about symptom severity, demographics,
      medication use, and health behaviors. Patients were compared by current PPI use,
      and statistical analyses were performed by using SAS version 9.2 software.
      RESULTS: Thirty-eight patients (42.2%) reported current PPI use despite a
      negative result from a pH study. Only 17 patients (18.9%) recalled being
      instructed to stop taking PPIs; chart review showed documented instructions to
      stop PPI therapy for 15 patients (16.7%). There were no significant differences
      in demographic or clinical characteristics among patients compared by current PPI
      use. Patients taking a PPI were more likely than those not taking a PPI to report
      troublesome symptoms that affected their daily life, as measured by a
      questionnaire for the diagnosis of GERD (the GerdQ). CONCLUSIONS: More than 42%
      of patients with negative results from pH monitoring studies continue PPI therapy
      despite physiological data that they do not have GERD.

PMID- 22366178
TI  - Patients with autoimmune hepatitis who have antimitochondrial antibodies need
      long-term follow-up to detect late development of primary biliary cirrhosis.
AB  - Patients with autoimmune hepatitis (AIH) who have antibodies against
      mitochondrial proteins (AMA positive) are believed to have an autoimmune syndrome
      that should be managed as AIH. Of patients with AMA-positive AIH, we report on 3
      individuals to demonstrate how autoimmune liver disease can progress over time.
      Specific features of primary biliary cirrhosis (PBC) overlapped in time in these
      patients. Our observations indicate the importance of careful follow up of
      patients with AMA-positive AIH; health care professionals that treat such
      patients should therefore be aware of longitudinal clinical changes that might
      indicate development of PBC in this setting.

PMID- 22366179
TI  - Therapeutic end points in eosinophilic esophagitis: is elimination of esophageal
      eosinophils enough?

PMID- 22366180
TI  - Patients whose first episode of bleeding occurs while taking a beta-blocker have
      high long-term risks of rebleeding and death.
AB  - BACKGROUND & AIMS: Patients who have their first episode of variceal bleeding
      despite primary prophylaxis with a nonselective beta-adrenergic receptor
      antagonist (also called a nonselective beta-blocker [NSBB]) receive additional
      treatment by endoscopic band ligation to prevent further bleeding. However,
      little is known about their long-term outcomes. METHODS: We collected data on 89
      consecutive patients with cirrhosis who were admitted to the Liver Unit of
      Hospital Clinic, Barcelona, with acute esophageal variceal bleeding between June
      2007 and February 2011. Thirty-four patients were receiving primary prophylaxis
      with NSBBs when they had their first episode of variceal bleeding, whereas 55
      were not receiving NSBBs (controls). All patients were subsequently treated with
      a combination of endoscopic band ligation and NSBBs. Patients were examined after
      1, 3, and 6 months and every 6 months thereafter until 2 years. RESULTS: After 2
      years, a greater proportion of patients who had their first episode of bleeding
      while on NSBBs had further bleeding, compared with controls (48% vs 24%; P =
      .01). Primary prophylaxis with NSBBs and serum levels of bilirubin were
      independent predictors of rebleeding. Overall, 11 patients died, and 5 underwent
      liver transplantation. Liver transplantation-free survival was lower among
      patients who had their first episode of bleeding while taking NSBBs (66% vs 88%
      for controls; P = .02). Primary prophylaxis with NSBBs and Child-Pugh class were
      independently associated with liver transplantation-free survival. CONCLUSIONS:
      Patients who have their first episode of variceal bleeding while on primary
      prophylaxis with a beta-blocking agent have an increased risk of further bleeding
      and death, despite adding endoscopic band ligation. These patients possibly
      require alternative treatment approaches.

PMID- 22366181
TI  - Induction of thioredoxin-interacting protein is mediated by oxidative stress,
      calcium, and glucose after brain injury in mice.
AB  - Oxidative stress and glucose affect the expression of various genes that
      contribute to both reactive oxygen species generation and antioxidant systems.
      However, systemic alteration of oxidative stress-related gene expression in
      normal brains and in brains with a high-glucose status after ischemic-reperfusion
      has not been explored. Using a polymerase chain reaction array system, we
      demonstrate that thioredoxin-interacting protein (Txnip) is induced by both
      oxidative stress and glucose. We found that Txnip mRNA is induced by ischemic
      reperfusion injury and that Txnip is located in the cytoplasm of neurons.
      Moreover, in vitro oxygen-glucose deprivation (OGD) and subsequent reoxygenation
      without glucose and in vivo administration of 3-nitropropionic acid also promoted
      an increase in Txnip in a time-dependent manner, indicating that oxidative stress
      without glucose can induce Txnip expression in the brain. However, calcium
      channel blockers inhibit induction of Txnip after OGD and reoxygenation. Using
      the polymerase chain reaction array with ischemic and hyperglycemic-ischemic
      samples, we confirmed that enhanced expression of Txnip was observed in
      hyperglycemic-ischemic brains after middle cerebral artery occlusion. Finally,
      transfection of Txnip small interfering RNA into primary neurons reduced lactate
      dehydrogenase release after OGD and reoxygenation. This is the first report
      showing that Txnip expression is induced in neurons after oxidative or glucose
      stress under either ischemic or hyperglycemic-ischemic conditions, and that Txnip
      is proapoptotic under these conditions.

PMID- 22366182
TI  - Minocycline attenuates microglia activation and blocks the long-term
      epileptogenic effects of early-life seizures.
AB  - Innate immunity mediated by microglia appears to play a crucial role in
      initiating and propagating seizure-induced inflammatory responses. To address the
      role of activated microglia in the pathogenesis of childhood epilepsy, we first
      examined the time course of microglia activation following kainic acid-induced
      status epilepticus (KA-SE) in Cx3cr1(GFP/+) transgenic mice whose microglia are
      fluorescently labeled. We then determined whether this seizure-induced microglia
      activation primes the central immune response to overreact and to increase the
      susceptibility to a second seizure later in life. We used an inhibitor of
      microglia activation, minocycline, to block the seizure-induced inflammation to
      determine whether innate immunity plays a causal role in mediating the long-term
      epileptogenic effects of early-life seizure. First status epilepticus was induced
      at postnatal day (P) 25 and a second status at P39. KA-SE at P25 caused nearly a
      two-fold increase in microglia activation within 24h. Significant seizure-induced
      activation persisted for 7 days and returned to baseline by 14 days. P39 animals
      with prior exposure to KA-SE not only responded with greater microglial
      activation in response to "second hit" of KA, but shorter latency to express
      seizures. Inhibition of seizure-induced inflammation by 7 day minocycline post
      treatment abrogated both the exaggerated microglia activation and the increased
      susceptibility to the second seizure later in life. The priming effect of early
      life seizures is accompanied by modified and rapidly reactivated microglia. Our
      results suggest that anti-inflammatory therapy after SE may be useful to block
      the epileptogenic process and mitigate the long-term damaging effects of early
      life seizures.

PMID- 22366183
TI  - Functional recruitment of newborn hippocampal neurons after experimental stroke.
AB  - The adult brain responds to diverse pathologies such as stroke with increased
      generation of neurons in the dentate gyrus of the hippocampus. However, only
      little is known regarding the functional integration of newborn neurons into pre
      existing neuronal circuits. In this study, we investigated whether newborn
      neurons generated after experimental stroke are recruited for different
      behavioral tasks. Adult mice received photochemical cortical infarcts in the
      sensorimotor cortex and proliferating cells were labeled using the proliferation
      marker, bromodeoxyuridine. Eight weeks after stroke induction, the animals were
      trained to perform either a spatiotemporal task or a sensorimotor task. Immediate
      early gene expression (c-fos, Zif268) in newborn neurons was analyzed directly
      after the last session. Using this approach, we demonstrate that post-stroke
      generated neurons are recruited within the hippocampal networks. The sensorimotor
      task activates significantly more newborn neurons compared to the spatiotemporal
      task. Further experiments employing the two well-established stimulators of
      neurogenesis, enriched environment and voluntary wheel running, both
      significantly increase post-stroke neurogenesis in the dentate gyrus but do not
      affect the percentage of recruited neurons compared to controls. Significantly,
      the spatiotemporal task leads to a higher portion of activated newborn neurons in
      the granule cell layer, suggesting a specific spatial activation pattern of new
      neurons in the dentate gyrus.

PMID- 22366184
TI  - Aeromonas hydrophila induced head kidney macrophage apoptosis in Clarias
      batrachus involves the activation of calpain and is caspase-3 mediated.
AB  - The mechanism of macrophage cytotoxicity induced by Aeromonas hydrophila is yet
      unresolved. We observed A. hydrophila induces Head Kidney Macrophage (HKM)
      apoptosis in Clarias batrachus, as evident from Hoechst 33342 and AnnexinV
      Propidium Iodide staining and presence of oligonucleosomal DNA ladder. Initiation
      of apoptosis required the bacteria to be alive, be actively phagocytosed into HKM
      and was dependent on host proteins. Elevated cytosolic calcium and consequent
      calpain activity that declined following pre-incubation with EGTA, verapamil and
      nifedipine implicates the role of calcium influx through voltage gated calcium
      channels and calpain in A. hydrophila-induced HKM apoptosis. Though, calpain-1
      and -2 were involved, calpain-2 appeared to be more important in the process.
      EGTA, verapamil, nifedipine and calpain-2 inhibitor reduced caspase-3 activity
      and apoptosis. We conclude that A. hydrophila alters cytosolic calcium
      homeostasis initiating the activation of calpains, more specifically calpain-2,
      which leads to caspase-3 mediated HKM apoptosis in C. batrachus.

PMID- 22366185
TI  - A comparative overview of immunoglobulin genes and the generation of their
      diversity in tetrapods.
AB  - In the past several decades, immunoglobulin (Ig) genes have been extensively
      characterized in many tetrapod species. This review focuses on the expressed Ig
      isotypes and the diversity of Ig genes in mammals, birds, reptiles, and
      amphibians. With regard to heavy chains, five Ig isotypes - IgM, IgD, IgG, IgA,
      and IgE - have been reported in mammals. Among these isotypes, IgM, IgD, and IgA
      (or its analog, IgX) are also found in non-mammalian tetrapods. Birds, reptiles,
      and amphibians express IgY, which is considered the precursor of IgG and IgE.
      Some species have developed unique isotypes of Ig, such as IgO in the platypus,
      IgF in Xenopus, and IgY (DeltaFc) in ducks and turtles. The kappa and lambda
      light chains are both utilized in tetrapods, but the usage frequencies of kappa
      and lambda chains differ greatly among species. The diversity of Ig genes depends
      on several factors, including the germline repertoire and recombinatorial and
      post-recombinatorial diversity, and different species have evolved distinct
      mechanisms to generate antibody diversity.

PMID- 22366186
TI  - Intracellular pH regulation by Na+/H+ exchanger-1 (NHE1) is required for growth
      factor-induced mammary branching morphogenesis.
AB  - Regulation of intracellular pH (pHi) and protection against cytosolic
      acidification is primarily a function of the ubiquitous plasma membrane
      Na+/H+exchanger-1 (NHE1), which uses a highly conserved process to transfer
      cytosolic hydrogen ions (H+) across plasma membranes in exchange for
      extracellular sodium ions (Na+). Growth factors, which are essential regulators
      of morphogenesis, have also been found to be key activators of NHE1 exchanger
      activity; however, the crosstalk between both has not been fully evaluated during
      organ development. Here we report that mammary branching morphogenesis induced by
      transforming growth factor-alpha (TGFalpha) requires PI3K-dependent NHE1
      activation and subsequent pHi alkalization. Inhibiting NHE1 activity after
      TGFalpha stimulation with 10 MUM of the NHE1-specific inhibitor N-Methyl-N
      isobutyl Amiloride (MIA) dramatically disrupted branching morphogenesis, induced
      extensive proliferation, ectopic expression of the epithelial hyper-proliferative
      marker Keratin-6 and sustained activation of MAPK. Together these findings
      indicate a novel developmental signaling cascade involving TGFalpha>PI3K>NHE1>pHi
      alkalization, which leads to a permissible environment for MAPK negative feedback
      inhibition and thus regulated mammary branching morphogenesis.

PMID- 22366187
TI  - Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace
      Tc 99m bone scanning and computed tomography for single-step detection of
      metastases in patients with high-risk prostate cancer?
AB  - BACKGROUND: Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced
      computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and
      abdomen are universally recommended for detecting prostate cancer (PCa)
      metastases in cancer of all stages. However, this two-step approach has limited
      sensitivity and specificity. OBJECTIVE: Evaluate the diagnostic accuracy of whole
      body MRI (WBMRI) as a one-step screening test for PCa metastases. DESIGN,
      SETTING, AND PARTICIPANTS: One hundred consecutive PCa patients at high risk for
      metastases prospectively underwent WBMRI, CT, and BS completed with targeted x
      rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the
      images. MEASUREMENTS: This study compares the diagnostic performance of WBMRI,
      CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC)
      receiver operator characteristics. A best valuable comparator (BVC) approach was
      used to adjudicate final metastatic status in the absence of pathologic
      evaluation. RESULTS AND LIMITATIONS: Based on the BVC, 68 patients had
      metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was
      86% and 98-100%, respectively (p<0.04), and specificity was 98% and 98-100%,
      respectively. The first and second WBMRI readers respectively identified bone
      metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT
      and WBMRI for detecting enlarged lymph nodes was similar, at 77-82% for both;
      specificity was 95-96% and 96-98%, respectively. The sensitivity of the
      combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or
      enlarged lymph nodes was 84% and 91-94%, respectively (p=0.03-0.10);
      specificities were 94-97% and 91-96%, respectively. The 95% confidence interval
      of the difference between the AUC of the worst WBMRI reading and the AUC of any
      of the BS/TXR plus CT lay within the noninferiority margin of +/-10% AUC.
      CONCLUSIONS: WBMRI outperforms BS/TXR in detecting bone metastases and performs
      as well as CT for enlarged lymph node evaluation. WBMRI can replace the current
      multimodality metastatic work-up for the concurrent evaluation of bones and lymph
      nodes in high-risk PCa patients.

PMID- 22366188
TI  - Robotic extended pelvic lymphadenectomy for intermediate- and high-risk prostate
      cancer.
AB  - BACKGROUND: Accurate staging of prostate cancer is enhanced by a thorough
      evaluation of the pelvic lymph nodes. Limited data are available regarding
      robotic extended pelvic lymphadenectomy (PLA) in this setting. OBJECTIVE: Analyze
      our experience performing robotic extended PLA. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 143 consecutive men with intermediate- or high-risk
      clinically localized adenocarcinoma of the prostate underwent robotic extended
      PLA and radical prostatectomy between September 2010 and November 2011 by a
      single surgeon. SURGICAL PROCEDURE: Lymph node packets were sent separately from
      bilateral common, external, and internal iliacs, obturators, node of Cloquet, and
      anterior prostatic fat. MEASUREMENTS: Descriptive statistics were used to
      summarize lymph node yields and positive nodes. Clinical variables were examined
      in logistic regression models to predict lymph node positivity. RESULTS AND
      LIMITATIONS: Median lymph node yield was 20 (range: 9-65, interquartile range: 15
      25). Eighteen patients (13%) were found to have metastatic prostate cancer in the
      lymph nodes. The mean number of positive nodes found was 2.9 (range: 1-11). In 14
      of 18 node-positive patients (78%), the extent of nodal invasion was outside the
      boundaries of a limited PLA. For four patients with positive nodes (22%),
      prostate biopsy predicted unilateral disease but PLA revealed contralateral
      positive lymph nodes. A total of 82% of patients experienced no complications,
      and most Clavien grade 1-2 complications consisted of anastomotic leakage,
      urinary retention, ileus, and lymphocele. Only 4% of patients experienced a grade
      3 complication. Under multivariate regression analysis, prostate-specific antigen
      (PSA), clinical stage, and maximum biopsy core tumor volume were identified as
      significant predictors of finding positive pelvic lymph nodes (area under the
      curve: 91%). The main limitations include short follow-up and lack of
      randomization. CONCLUSIONS: Robotic extended bilateral PLA for prostate cancer up
      to the common iliac bifurcation increases nodal yield and positive nodal rate and
      can be performed safely. PSA, clinical stage, and maximum biopsy core volume are
      predictors for lymph node invasion. Long-term follow-up is needed to evaluate for
      therapeutic benefit.

PMID- 22366189
TI  - Characterization of a multidrug-resistant Acinetobacter baumannii strain carrying
      the blaNDM-1 and blaOXA-23 carbapenemase genes from the Czech Republic.

PMID- 22366190
TI  - Association of intron 1 variants of the dopamine transporter gene with
      schizophrenia.
AB  - The dopamine transporter (DAT1) gene has been implicated in the pathogenesis of
      many neuropsychiatric disorders, including schizophrenia. The present study aimed
      to investigate association of the DAT1 gene polymorphisms with schizophrenia in a
      Han Chinese population. Two single nucleotide polymorphisms (SNPs) in the DAT1
      gene (rs2975223 and rs2455391) were tested in 368 patients with schizophrenia and
      420 healthy controls, of whom 293 patients underwent an assessment of psychotic
      symptoms through the positive and negative syndrome scale (PANSS). The chi-square
      test (chi(2)) showed disease association for rs2455391 (corrected p=0.023 for
      allelic association and p=0.034 for genotypic association, respectively). The
      rs2975223(G)-rs2455391(C) haplotype was associated with increased risk of the
      illness (p=0.0012, OR=2.09, 95% CI=1.28-3.42). Quantitative trait analysis showed
      that rs2455391 was associated with positive symptoms, general symptoms and global
      symptoms but not with negative symptoms. The present results suggest that the
      DAT1 gene may be mainly involved in the development of the positive symptoms in
      the Chinese population.

PMID- 22366191
TI  - Subthreshold electrical stimulation reduces motor unit discharge variability and
      decreases the force fluctuations of plantar flexion.
AB  - The purpose of this study was to examine the influence of subthreshold electrical
      stimulation on the force fluctuations and motor-unit discharge variability during
      low-level, steady contraction of the plantar flexor muscles. Seven subjects
      performed a force-matching task of isometric plantar flexion at 5% of maximal
      voluntary contraction with and without random electrical stimulation applied to
      the tibial nerve. During the task, the motor unit action potential was
      continuously recorded with fine-wire electrodes, and the inter-spike intervals of
      a single motor unit were calculated. The coefficient of variation (CV) of the
      force fluctuations and the inter-spike intervals of the motor unit discharge were
      significantly decreased by the intervention of subthreshold electrical
      stimulation, although there were no changes in the mean values. These results
      suggest that subthreshold stimulation reduced the motor-unit discharge
      variability, which in turn, increased the steadiness of the force.

PMID- 22366192
TI  - The role of Irf6 in tooth epithelial invagination.
AB  - Thickening and the subsequent invagination of the epithelium are an important
      initial step in ectodermal organ development. Ikkalpha has been shown to play a
      critical role in controlling epithelial growth, since Ikkalpha mutant mice show
      protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium
      rather than invagination. We show here that mutation of the Interferon regulatory
      factor (Irf) family, Irf6 also results in evagination of incisor epithelium. In
      common with Ikkalpha mutants, Irf6 mutant evagination occurs in a NF-kappaB
      independent manner and shows the same molecular changes as those in Ikkalpha
      mutants. Irf6 thus also plays a critical role in regulating epithelial
      invagination. In addition, we also found that canonical Wnt signaling is
      upregulated in evaginated incisor epithelium of both Ikkalpha and Irf6 mutant
      embryos.

PMID- 22366194
TI  - 3,5,3'-triiodothyronine (T3) stimulates cell proliferation through the activation
      of the PI3K/Akt pathway and reactive oxygen species (ROS) production in chick
      embryo hepatocytes.
AB  - Thyroid hormones (THs) have a wide variety of essential roles in vertebrates,
      ranging from the regulation of key metabolic processes to cell proliferation and
      apoptosis. The classical mechanism of action of THs is genomic; 3,5,3'
      triiodothyronine (T3) binds to specific nuclear receptors (TRs) and modifies the
      expression of specific genes. Recently, a new category of mechanisms, termed
      nongenomic, has been discovered for T3. These mechanisms include, among others,
      the rapid activation of signal transduction pathways, such as PI3K/Akt and MAPK,
      which eventually lead to cell proliferation. These effects are mediated in some
      cell types by a plasma membrane receptor, identified as integrin alphavbeta3, and
      in other cell types by cytoplasmic TRbeta1. The aim of this work was to analyze
      the effect of T3 on the cell growth of chick embryo hepatocytes at two different
      stages of development, 14 and 19 days, and to determine the activation of the
      signal transduction pathways, focusing on the potential involvement of a plasma
      membrane receptor and the possible participation of PI3K/Akt and reactive oxygen
      species (ROS). Our results clearly show that T3 stimulates cell proliferation at
      both stages of development through the activation of the PI3K/Akt pathway and the
      production of small amounts of ROS, which operate as effective second messengers.
      Moreover, we prove that these effects are not initiated at the plasma membrane
      receptor for T3.

PMID- 22366193
TI  - Pharmacologic effects of 2-methoxyestradiol on angiotensin type 1 receptor down
      regulation in rat liver epithelial and aortic smooth muscle cells.
AB  - BACKGROUND: Delayed onset of cardiovascular disease (CVD) in female patients is
      not well understood, but could be due in part to the protective effect of
      estrogen before menopause. Experimental studies have identified the angiotensin
      type 1 receptor (AT1R) as a key factor in the progression of CVD. OBJECTIVE: We
      examined the effects of the estrogen metabolite 2-methoxyestradiol (2ME2) on AT1R
      expression. METHODS: Rat liver cells were exposed to 2ME2 for 24 hours, and
      angiotensin II (AngII) binding and AT1R mRNA expressions were assessed. RESULTS:
      In the presence of 2ME2, cells exhibited significant down-regulation of AngII
      binding that was both dose and time dependent, independent of estrogen receptors
      (ERalpha/ERbeta). Down-regulation of AngII binding was AT1R specific, with no
      change in receptor affinity. Under similar conditions, we observed lower
      expression of AT1R mRNA, significant inhibition of AngII-mediated increase in
      intracellular Ca(2+), and increased phosphorylation of ERK1/2. Pretreatment of
      cells with the MEK inhibitor PD98059 prevented 2ME2-induced ERK1/2
      phosphorylation and down-regulation of AT1R expression, which suggests that the
      observed inhibitory effect is mediated through ERK1/2 signaling intermediates.
      Similar analyses in stably transfected CHO (Chinese hamster ovary) cell lines
      with a constitutively active cytomegalovirus promoter showed no change in AT1R
      expression, which suggests that 2ME2-mediated effects are through transcriptional
      regulation. The effects of 2ME2 on AT1R down-regulation through ERK1/2 were
      consistently reproduced in primary rat aortic smooth muscle cells. CONCLUSIONS:
      Because AT1R has a critical role in the control of CVD, 2ME2-induced changes in
      receptor expression may provide beneficial effects to the cardiovascular and
      other systems.

PMID- 22366195
TI  - Association between circulating osteoblast progenitor cells and aortic
      calcifications in women with postmenopausal osteoporosis.
AB  - BACKGROUND AND AIMS: Ectopic artery calcification has been documented in women
      with postmenopausal osteoporosis, in whom an imbalance in the number of
      circulating osteoprogenitor cells (OPCs) has been identified. Circulating OPCs
      form calcified nodules in vitro; however, it remains unknown whether an
      association exists between the number of circulating OPCs and aortic
      calcifications. We investigated the relationship between OPCs and aortic
      calcifications in women with postmenopausal osteoporosis. METHODS AND RESULTS:
      The number of circulating OPCs was quantified by FACS analysis in 50 osteoporotic
      postmenopausal women. OPCs were defined as CD15-/alkaline-phosphatase(AP)+ cells
      coexpressing or not CD34. Participants underwent measurement of markers of bone
      metabolism, bone mineral density and abdominal aortic calcium (AAC) by 64-slice
      computed tomography. Patients with AAC were older, had lower 25(OH)vitamin D
      levels and higher circulating CD15-/AP+/CD34- cells than those without AAC.
      Significant correlates of AAC included age (rho = 0.38 p = 0.006), calcium (rho =
      0.35 p = 0.01), 25(OH)vitamin D (rho = -0.31, p = 0.03) and the number of CD15
      /AP+/CD34- cells (rho = 0.55 p < 0.001). In regression analyses, the log
      transformed number of CD15-/AP+/CD34- cells was associated with the presence (OR
      = 6.45, 95% CI 1.03-40.1, p = 0.04) and severity (beta = 0.43, p < 0.001) of AAC,
      independent of age, 25(OH)vitamin D, calcium and other potential confounders.
      Patients with low 25(OH)vitamin D and high CD15-/AP+/CD34- cells had higher
      median AAC than other patients (1927/MUL, 862-2714/MUL vs 147/MUL, 0-1665/MUL, p
      = 0.003). CONCLUSION: In women with postmenopausal osteoporosis, the number of
      circulating CD15-/AP+/CD34- cells is significantly associated with increased
      aortic calcifications, that appear to be correlated also with reduced
      25(OH)vitamin D levels.

PMID- 22366196
TI  - Safety and pharmacokinetics of multiple doses of aclidinium bromide administered
      twice daily in healthy volunteers.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by progressive
      airway obstruction and increased cholinergic tone. The global initiative for
      chronic obstructive lung disease (GOLD) guidelines recommend long-acting
      anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel,
      long-acting muscarinic antagonist developed for the treatment of COPD. A phase I,
      randomized, single-blind, multiple-dose clinical trial was conducted to assess
      the safety and pharmacokinetics (PK) of multiple doses of twice-daily (BID)
      aclidinium in healthy subjects. Thirty healthy male and female subjects received
      aclidinium 200 MUg, 400 MUg, 800 MUg, or placebo twice daily for 7 days. Subjects
      were randomized to 1 of 3 cohorts and 10 subjects in each cohort were randomized
      (8:2) to either aclidinium or placebo groups. Safety was assessed via adverse
      events (AEs), laboratory evaluations, vital signs, and ECGs. Plasma samples were
      obtained at multiple time points throughout the study and analyzed for aclidinium
      and its inactive acid and alcohol metabolites using a fully validated method of
      liquid chromatography coupled with tandem mass spectrometry. A total of 9
      treatment-emergent AEs were reported (1, placebo; 3, aclidinium 400 MUg; 5,
      aclidinium 800 MUg), all of which were mild in severity. No serious AEs were
      reported. There were no clinically meaningful changes in laboratory parameters or
      vital signs. PK parameters on Day 7 following BID dosing of aclidinium showed
      that steady state was achieved for aclidinium and its metabolites. On Days 1 and
      7, maximum plasma concentrations (Cmax) of aclidinium were generally observed at
      the first PK time point (5 min postdose) and rapidly declined, with plasma
      concentrations generally less than 10% of Cmax by 6 h postdose in all aclidinium
      groups. Mean effective t(1/2) after the evening dose on Day 7 ranged from 4.6 to
      7.0 h for aclidinium 400 MUg and 800 MUg, similar to the terminal t(1/2) observed
      on Day 1 (4.5-5.9 h). Exposure for aclidinium and both metabolites increased with
      increasing dose, with the increase in exposure being less than dose proportional
      between the 400 MUg and 800 MUg doses. Overall, all doses of aclidinium were safe
      and well tolerated throughout the study. Pharmacokinetic steady state was reached
      for aclidinium and both metabolites within the 7-day treatment period for all
      doses tested. Aclidinium bromide exhibited time-independent PK following dosing
      to steady state, indicating that similar concentration versus time profiles will
      occur after repeated administration at the same dose and frequency.

PMID- 22366197
TI  - Elastin in asthma.
AB  - Extracellular matrix is generally increased in asthma, causing thickening of the
      airways which may either increase or decrease airway responsiveness, depending on
      the mechanical requirements of the deposited matrix. However, in vitro studies
      have shown that the altered extracellular matrix produced by asthmatic airway
      smooth muscle cells is able to induce increased proliferation of non-asthmatic
      smooth muscle cells, which is a process believed to contribute to airway hyper
      responsiveness in asthma. Elastin is an extracellular matrix protein that is
      altered in asthmatic airways, but there has been no systematic investigation of
      the functional effect of these changes. This review reveals divergent reports of
      the state of elastin in the airway wall in asthma. In some layers of the airway
      it has been described as increased, decreased and/or fragmented, or unchanged.
      There is also considerable evidence for an imbalance of matrix
      metalloproteinases, which degrade elastin, and their respective inhibitors the
      tissue inhibitors of metalloproteinases, which collectively help to explain
      observations of both increased elastin and elastin fragments. A loss of lung
      elastic recoil in asthma suggests a mechanical role for disordered elastin in the
      aetiology of the disease, but extensive studies of elastin in other tissues show
      that elastin fragments elicit cellular effects such as increased proliferation
      and inflammation. This review summarises the current understanding of the role of
      elastin in the asthmatic airway.

PMID- 22366198
TI  - Ras/ERK1 pathway regulation of p27KIP1-mediated G1-phase cell-cycle arrest in
      cordycepin-induced inhibition of the proliferation of vascular smooth muscle
      cells.
AB  - Cordycepin, the main constituent of Cordyceps militaris, demonstrated an anti
      atherogenic effect in experimental animals. However, the effects of cordycepin on
      cell-cycle regulation and the signaling pathway in vascular smooth muscle cells
      (VSMC) remain largely unknown; therefore, unexpected roles of cordycepin-induced
      inhibition in VSMC growth were investigated. Mechanisms in cordycepin-treated
      VSMC were examined via an MTT assay, a thymidine uptake experiment, FACS
      analysis, immunoblot analysis, kinase assay, immunoprecipitation assay, and
      transient transfection assays. Cordycepin inhibited cell growth, induced G1-phase
      cell-cycle arrest, down-regulated cyclins and cyclin-dependent kinase (CDK)
      expression, and up-regulated p27KIP1 expression in VSMC. Cordycepin induced
      activation of JNK, p38MAPK and ERK1/2. Blocking of the ERK function using either
      ERK1/2-specific inhibitor U0126 or a small interfering RNA (si-ERK1) reversed
      p27KIP1 expression, inhibition of cell growth, and decreased cell-cycle proteins
      in cordycepin-treated VSMC. Ras activation was increased by cordycepin.
      Transfection of cells with dominant negative Ras (RasN17) mutant genes rescued
      cordycepin-induced ERK1/2 activity, increased p27KIP1 expression, inhibited cell
      proliferation, and reduced cell cycle proteins. In conclusion, our findings
      indicate that Ras/ERK1 pathways participate in p27KIP1-mediated G1-phase cell
      cycle arrest induced by cordycepin via a decrease in cyclin/CDK complexes in
      VSMC.

PMID- 22366199
TI  - Carnosine has antinociceptive properties in the inflammation-induced nociceptive
      response in mice.
AB  - Carnosine is a biologically active dipeptide that is found in fish and chicken
      muscle. Recent studies have revealed that carnosine has neuroprotective activity
      in zinc-induced neural cell apoptosis and ischemic stroke. In the present study,
      we examined the expression of carnosine in the spinal cord, and the
      antinociceptive potency of carnosine in a mouse model of inflammation-induced
      nociceptive pain. Immunohistochemical studies with antiserum against carnosine
      showed an abundance of carnosine-immunoreactivity in the dorsal horn of the mouse
      spinal cord. Double-immunostaining techniques revealed that carnosine was
      expressed in the neurons and astrocytes in the spinal cord. Oral administration
      of carnosine attenuated the number of writhing behaviors induced by the
      intraperitoneal administration of 0.6% acetic acid. Treatment with carnosine also
      attenuated the second phase, but not the first phase, of the nociceptive response
      to formalin. Moreover, intrathecal, but not intraplanter, administration of
      carnosine attenuated the second phase of the nociceptive response to formalin.
      Our immunohistochemical and behavioral data suggest that carnosine has
      antinociceptive effects toward inflammatory pain, which may be mediated by the
      attenuation of nociceptive sensitization in the spinal cord.

PMID- 22366200
TI  - Differential effects of sulfonylurea derivatives on vascular ATP-sensitive
      potassium channels.
AB  - Sulfonylurea drugs exert their insulinotropic action by inhibiting ATP-sensitive
      potassium channels in the pancreas. However, these channels are also expressed in
      myocardial and vascular smooth muscle, implicating possible detrimental
      cardiovascular effects. Aim of the present study was to investigate the
      inhibitory potency of various widely used sulfonylurea drugs in resistance
      arteries. Isolated mesenteric and renal resistance arteries mounted in a myograph
      and isolated perfused kidneys were used to measure drug responses. Pinacidil
      induced a dose-dependent relaxation of phenylephrine preconstricted mesenteric
      and renal arteries (pEC(50)=6.10 +/- 0.01 and 5.66 +/- 0.03, respectively).
      Schild plot analysis of pinacidil relaxation curves in mesenteric arteries in the
      presence of sulfonylurea antagonists revealed the following order of potency:
      glimepiride (pA(2)=7.22) >= glibenclamide (pA(2)=7.05) > glipizide (pA(2)=5.25) >
      gliclazide (pA(2)=4.31). The effects of glibenclamide in renal arteries were
      comparable. Furthermore, glibenclamide produced similar constrictive properties
      in isolated renal arteries as in isolated perfused whole kidneys. We conclude
      that sulfonylurea drugs exert differential effects on vascular smooth muscle
      K(ATP) channels. Our results suggest that glibenclamide and glimepiride will
      interact with these channels at therapeutic concentrations.

PMID- 22366201
TI  - Molecular events associated with Macrovipera lebetina obtusa and Montivipera
      raddei venom intoxication and condition of biomembranes.
AB  - Studies on the interaction of snake venom and organized lipid interfaces have
      been conducted using a variety of systems, including BLMs, SUVs and GUVs. The
      present study was undertaken to elucidate how the plastic properties (namely, its
      microviscosity, thickness, permeability) of model membranes from native lipids of
      different tissues of rats change in the course of Macrovipera lebetina obtusa
      (MLO), Montivipera raddei (MR) and Naja kaouthia (NK) venoms processing. The
      presence of viper venom in organism leads to increasing of the electrical
      resistance of BLMs from liver and muscle lipids approximately on a sequence,
      while the BLMs from brain lipids have not shown noticeable differences of plastic
      properties compared to the control. Giant unilamellar vesicles (GUVs) with a mean
      diameter of 30MUm have a minimum curvature and mimic cell membranes in this
      respect. Snake venom was added to the sample chamber before the vesicles were
      formed. The membrane fluorescence probes, ANS and pyrene, were used to assess the
      state of the membrane and specifically mark the phospholipid domains. Fluorescent
      spectra were acquired on a Varian fluorometer instrument. ANS and pyrene allow us
      to quantify the fluidity changes in the membrane by measuring of the fluorescence
      intensity. The presence of viper venom in GUVs media reveals a noticeable
      decreasing of membrane fluidity compared to the control, while the binding of
      fluorophores with GUVs modified by venom leads to the appearance of channel
      activity. These studies also emphasize the importance of a membrane surface
      curvature for its interaction with enzymatic components of venom.

PMID- 22366202
TI  - Interactions of the intact FsrC membrane histidine kinase with its pheromone
      ligand GBAP revealed through synchrotron radiation circular dichroism.
AB  - FsrC is the membrane-bound histidine kinase component of the Fsr two-component
      signal transduction system involved in quorum sensing in the hospital-acquired
      infection agent Enterococcus faecalis. Synchrotron radiation circular dichroism
      spectroscopy was used here to study the intact purified protein solubilised in
      detergent micelles. Conditions required for FsrC stability in detergent were
      firstly determined and tested by prolonged exposure of stabilised protein to far
      ultraviolet radiation. Using stabilised purified protein, far-ultraviolet
      synchrotron radiation circular dichroism revealed that FsrC is 61% alpha-helical
      and that it is relatively thermostable, retaining at least 57% secondary
      structural integrity at 90 degrees C in the presence or absence of gelatinase
      biosynthesis-activating pheromone (GBAP). Whilst binding of the quorum pheromone
      ligand GBAP did not significantly affect FsrC secondary structure, near
      ultraviolet spectra revealed that the tertiary structure in the regions of the
      Tyr and Trp residues was significantly affected. Titration experiments revealed a
      calculated kd value of 2 microM indicative of relatively loose binding
      ofgelatinase biosynthesis-activating pheromone to FsrC. Although use of
      synchrotron radiation circular dichroism has been applied to membrane proteins
      previously, to our knowledge this is the first report of its use to determine a
      kd value for an intact membrane protein. Based on our findings, we suggest that
      synchrotron radiation circular dichroism will be a valuable technique for
      characterising ligand binding by other membrane sensor kinases and indeed other
      membrane proteins in general. It further provides a valuable screening tool for
      membrane protein stability under a range of detergent conditions prior to
      downstream structural methods such as crystallisation and NMR experiments
      particularly when lower detergent concentrations are used.

PMID- 22366203
TI  - Methylation of ethanolamine groups in phosphoethanolamines is relevant for L
      arginine insertion in lipid membranes.
AB  - The interaction of L-arginine with membranes composed by phospholipids with
      different degrees of methylation of the ethanolamine group was studied by means
      of surface and dipole potentials and surface pressure variations. The subsequent
      methylation of the amine head group appears to hinder the synergic response of
      the adsorption observed in phosphatidylethanolamine membranes. The kinetics of
      the binding process denotes that the methyl groups are relevant in regulating the
      specific interaction of the amino acid with the interface by hydrogen bonds. This
      response can be put in correlation with the function of signal transduction
      assigned previously to methyl lipids [F. Hirata and J. Axelrod, 1980] and appears
      to be relevant to understand the mechanism of insertion of arginine residues in
      peptides of biological interest.

PMID- 22366204
TI  - Ethanol perturbs lipid organization in models of stratum corneum membranes: An
      investigation combining differential scanning calorimetry, infrared and (2)H NMR
      spectroscopy.
AB  - Ethanol is used in a variety of topical products. It is known to enhance the
      permeability of the skin by altering the ability of the stratum corneum (SC)
      intercellular membranes to form an effective barrier. In addition, ethanol and
      other alcohols are key components of antiseptic gels currently used for hand
      wash. Using infrared and deuterium NMR spectroscopy as well as calorimetry, we
      have investigated the effect of ethanol on a model membrane composed of lipids
      representing the three classes of SC lipids, an equimolar mixture of N
      palmitoylsphingosine (ceramide), palmitic acid and cholesterol. Ethanol is found
      to influence the membrane in a dose dependent manner, disrupting packing and
      increasing lipid motion at low concentrations and selectively extracting lipids
      at moderate concentrations.

PMID- 22366205
TI  - Novel ether lipid cardiolipins in archaeal membranes of extreme haloalkaliphiles.
AB  - The lipidome of two extremely haloalkaliphilic archaea, Natronococcus occultus
      and Natronococcus amylolyticus, has been examined by means of combined thin-layer
      chromatography and MALDI-TOF/MS analyses. The detailed investigation of lipid
      profiles has confirmed the presence of i) ether lipid phosphatidylglycerol and
      phosphatidylglycerophosphate methyl ester as main lipid components, ii) both
      C(20) and C(25) isopranoid chains in the lipid core and yielded new findings on
      membrane lipids of these unusual organisms. Besides some novel minor or trace
      phospholipids and glycolipids, data indicate the presence of ether lipid
      cardiolipin variants constituted by different combinations of C(20) and C(25)
      isopranoid chains, never before described in archaea. The role of C(25)
      isopranoid chains in the adaptation to high pH gradients in the presence of very
      high salt concentrations is discussed.

PMID- 22366206
TI  - Risk factors for community-associated methicillin-resistant Staphylococcus aureus
      infection in Hong Kong.
AB  - OBJECTIVES: The risk factors for community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) infection were not well understood. The objective
      of this study was to identify risk factors associated with CA-MRSA infection in
      Hong Kong. METHODS: We carried out a matched case control study. Cases and
      controls were recruited from 14 acute public hospitals in Hong Kong. One control
      was individually matched to one case based on sex, age, admission date and ward
      location. We interviewed each case and control by telephone using a standard
      questionnaire. We used a conditional logistic regression model for multivariate
      analysis. RESULTS: We successfully recruited 127 pairs of matched case and
      control. We found that sharing of personal items with other persons had a higher
      risk of CA-MRSA infection (Adjusted matched odds ratio [aOR]: 4.71, 95%
      confidence interval [CI] 1.43-15.59). On the other hand, patients who had
      frequent hand washing practice (aOR: 0.21, 95%CI 0.06-0.72) and those who
      reported history of acne (aOR: 0.12, 95%CI 0.02-0.74) had a lower risk of CA-MRSA
      infection. CONCLUSIONS: We concluded that sharing of personal items with other
      persons is a risk factor for CA-MRSA infection while frequent hand washing is a
      protective factor against the infection.

PMID- 22366207
TI  - Pulmonary Mycobacterium abscessus: a canary in the cystic fibrosis coalmine.
AB  - We present a case of pulmonary nontuberculous mycobacterial infection (PNTM) with
      M. abscessus. After exclusion of genetic immune disorders known to cause NTM
      susceptibility, we found compound heterozygosity of two mutations, F508del and
      R117H in CFTR. The combination of F508del with a hypomorphic CFTR mutation can
      cause a mild Cystic Fibrosis (CF) phenotype with delayed CF symptoms in
      adulthood. Although the patient was continuously treated for her lung infection
      by different physicians for more than twenty years, the diagnosis CF had been
      missed. The forme fruste of CF should be considered in the analysis of host
      factors predisposing for PNTM.

PMID- 22366208
TI  - Clinicopathological features of sudden unexpected infectious death: population
      based study in children and young adults.
AB  - INTRODUCTION AND OBJECTIVES: Infectious diseases are one of the major causes of
      sudden death, but data of sudden unexpected death from infectious diseases
      (SUDID) are sparse in children and young people. The aim of this study is to
      analyse their epidemiological, clinical, pathological and microbiological
      characteristics. METHODS: Population observational study of all deaths due to
      infectious diseases in people aged 0-34 years in Biscay between 1991 and 2010.
      The data of Mortality Register and Forensic Pathology Service were analysed. The
      SUDID cases in which a forensic autopsy was performed were identified. RESULTS:
      There were 56 SUDID cases (16% of the all sudden deaths). Myocarditis (n=20) and
      acute bacterial bronchopneumonia/pneumonia (n=18) were the most frequent causes,
      followed by meningococcemia (n=5) and viral pneumonia (n=4). A chronic co-morbid
      condition (mainly drug abuse in young people and moderate low birth weight in
      infants) was recorded in one-third and prodromal symptoms in two-thirds.
      Seventeen young people had consumed illegal drugs and/or methadone. In 17 of the
      23 autopsies where microbiological analyses were performed, the organism
      responsible was identified. The incidence of SUDID was 0.6/100000
      inhabitants/year, representing 5% of all deaths from infectious diseases. SUDID
      rate was 1.87 times higher in males than in females. The highest incidence
      occurred in infants (3.7). CONCLUSIONS: SUDID is infrequent, but it represents a
      significant proportion of all sudden deaths in children and young people. The
      relationship between methadone and bronchopneumonia is noticeable. This article
      stresses the importance of microbiological analyses in SUDID. Investigation based
      on forensic pathology provides useful epidemiologic, clinico-pathological and
      microbiological information for prevention of infectious diseases.

PMID- 22366209
TI  - Arabidopsis Hexokinase-Like1 and Hexokinase1 form a critical node in mediating
      plant glucose and ethylene responses.
AB  - Arabidopsis (Arabidopsis thaliana) Hexokinase-Like1 (HKL1) lacks glucose (Glc)
      phosphorylation activity and has been shown to act as a negative regulator of
      plant growth. Interestingly, the protein has a largely conserved Glc-binding
      domain, and protein overexpression was shown previously to promote seedling
      tolerance to exogenous 6% (w/v) Glc. Since these phenotypes occur independently
      of cellular Glc signaling activities, we have tested whether HKL1 might promote
      cross talk between the normal antagonists Glc and ethylene. We show that
      repression by 1-aminocyclopropane-1-carboxylic acid (ACC) of the Glc-dependent
      developmental arrest of wild-type Arabidopsis seedlings requires the HKL1
      protein. We also describe an unusual root hair phenotype associated with growth
      on high Glc medium that occurs prominently in HKL1 overexpression lines and in
      glucose insensitive 2-1 (gin2-1), a null mutant of Hexokinase1 (HXK1). Seedlings
      of these lines produce bulbous root hairs with an enlarged base after transfer
      from agar plates with normal medium to plates with 6% Glc. Seedling transfer to
      plates with 2% Glc plus ACC mimics the high-Glc effect in the HKL1 overexpression
      line but not in gin2-1. A similar ACC-stimulated, bulbous root hair phenotype
      also was observed in wild-type seedlings transferred to plates with 9% Glc. From
      transcript expression analyses, we found that HKL1 and HXK1 have differential
      roles in Glc-dependent repression of some ethylene biosynthesis genes. Since we
      show by coimmunoprecipitation assays that HKL1 and HXK1 can interact, these two
      proteins likely form a critical node in Glc signaling that mediates overlapping,
      but also distinct, cellular responses to Glc and ethylene treatments.

PMID- 22366211
TI  - Does brain slices from pentylenetetrazole-kindled mice provide a more predictive
      screening model for antiepileptic drugs?
AB  - The cortical wedge is a commonly applied model for in vitro screening of new
      antiepileptic drugs (AEDs) and has been extensively used in characterization of
      well-known AEDs. However, the predictive validity of this model as a screening
      model has been questioned as, e.g., carbamazepine has been reported to lack
      effect in this model. The neuroplastic changes induced in acute and chronic
      animal models of epilepsy are known to affect the pharmacological profile of AEDs
      in vivo. Hence, we investigated whether brain slices from pentylenetetrazole
      (PTZ)-kindled animals could provide a more predictive screening model for AEDs.
      To this end, we compared the in vitro and in vivo pharmacological profile of
      several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin,
      valproate, and carbamazepine) along with citalopram using the PTZ-kindled model
      and brain slices from naive, saline-injected and PTZ-kindled mice. Our data
      suggest that the use of slices from PTZ-kindled mice in the cortical wedge does
      not increase the predictive validity of the model as an in vitro screening model
      for AEDs. Traditionally, the incidence of certain seizure types is widely used as
      a measure to characterize drug action in animal models of epilepsy. In our study,
      the anticonvulsant effect of the AEDs was investigated in vivo using several
      observational parameters (i.e., incidence and duration of convulsions, latency to
      clonic convulsions, and severity of convulsions). We found that including the
      observational parameter "severity" offered important additional information about
      the drug profile that would otherwise be lost if only a single parameter as
      "incidence" was used.

PMID- 22366210
TI  - Cysteinyl leukotrienes mediate the response of submucosal ganglia from rat colon
      to bradykinin.
AB  - The aim of the present study was to find out the mechanism by which the
      inflammatory mediator, bradykinin, induces an increase of the cytosolic Ca(2+)
      concentration ([Ca(2+)](i)) in enteric neurons. For this purpose, ganglia in the
      isolated submucosa from rat colon were loaded with the Ca(2+)-sensitive dye, fura
      2, and were exposed to bradykinin (2.10(-8)mol/l). Under control conditions, the
      kinin evoked a transient increase in [Ca(2+)](i). Preincubation with quinacrine
      or arachidonyltrifluoromethylketone (AACOCF(3)), i.e. blockers of cytosolic
      phospholipase A(2), prevented the raise of [Ca(2+)](i). This inhibition was
      mimicked by 5,8,11,14-eicosatetrayonic acid (ETYA), an inhibitor of
      cyclooxygenases as well as lipoxygenases, and by BWA4C, a selective inhibitor of
      lipoxygenases, whereas indomethacin was ineffective, suggesting the mediation of
      the kinin response by a lipoxygenase metabolite. Indeed, a leukotriene,
      leukotriene D(4) (LTD(4)), mimicked the effect of bradykinin. The LTD(4) receptor
      blocker, MK-571, inhibited the increase in [Ca(2+)](i) evoked by LTD(4) and by
      bradykinin. Consequently, bradykinin receptors in submucosal ganglia from rat
      colon are coupled to a stimulation of phospholipase A(2), the release of
      arachidonic acid and the production of LTD(4), which seems to be finally
      responsible for the change in the cytosolic Ca(2+) concentration.

PMID- 22366212
TI  - Evidence that 2-aminoethoxydiphenyl borate provokes fibrillation in perfused rat
      hearts via voltage-independent calcium channels.
AB  - We tested whether 2-aminoethoxydiphenyl borate (2-APB) induces arrhythmia in
      perfused rat hearts and whether this arrhythmia might result from the activation
      of voltage-independent calcium channels. Rat hearts were Langendorff perfused and
      beat under sinus rhythm. An isovolumic balloon inserted into the left ventricle
      was used to record mechanical function while bipolar electrograms were recorded
      from electrodes sutured to the base and the apex of hearts. Western and
      immunofluorescence analyses were performed on rat left ventricular protein
      extracts and left ventricular frozen sections, respectively. Rat ventricular
      myocytes express Orai 1 and Orai 3, and ventricle also contains the Orai
      regulator Stim1. Rat hearts (n=5) perfused with Krebs-Henseleit (KH) alone
      maintained sinus rhythm at 4.8 +/- 0.1 Hz and stable mechanical function. By
      contrast, perfusing hearts (n=5) with (KH+22 MUM 2-APB) provoked a period of
      tachycardic ectopy at rates of up to 10.8 +/- 0.2 Hz. As perfusion with (KH+22
      MUM 2-APB) continued, the rate of spontaneous ventricular depolarization
      increased to 21.8 +/- 1.2 Hz and became disorganized. Heart mechanical function
      collapsed as developed pressure decreased from 87 +/- 8.8 to 3.5 +/- 1.9 mm Hg.
      Flow rate did not change between normal (16.6 +/- 0.9 ml/min) and fibrillating
      (17.4 +/- 0.8 ml/min) hearts. The addition of 20 MUM 1-[2-(4-methoxyphenyl)-2-[3
      (4-methoxyphenyl) propoxy]ethyl-1H-imidazole (SKF-96365) to (KH+22 MUM 2-APB)
      perfusates (n=4) restored sinus rhythm and heart mechanical output. These data
      indicate that activating myocardial voltage-independent calcium channels,
      possibly the Orais, may be a novel cause of ventricular arrhythmia.

PMID- 22366213
TI  - Nicotinic acid induces antinociceptive and anti-inflammatory effects in different
      experimental models.
AB  - Although in vitro studies have shown that nicotinic acid inhibits some aspects of
      the inflammatory response, a reduced number of in vivo studies have investigated
      this activity. To the best of our knowledge, the effects induced by nicotinic
      acid in models of nociceptive and inflammatory pain are not known. Per os (p.o.)
      administration of nicotinic acid (250, 500 or 1000 mg/kg, -1 h) inhibited the
      first and the second phases of the nociceptive response induced by formalin in
      mice. Nicotinic acid (250 or 500 mg/kg, -1 and 3 h) also inhibited the mechanical
      allodynia induced by carrageenan in rats, a model of inflammatory pain. However,
      in a model of nociceptive pain, exposure of mice to a hot-plate, nicotinic acid
      was devoid of activity. In addition to inhibiting the nociceptive response in
      models of inflammatory pain, nicotinic acid (250 or 500 mg/kg, p.o., -1 and 3 h)
      inhibited paw edema induced by carrageenan in mice and rats. Picolinic acid (62.5
      or 125 mg/kg, p.o., -1 h), a nicotinic acid isomer, inhibited both phases of the
      nociceptive response induced by formalin, but not paw edema induced by
      carrageenan in mice. The other nicotinic acid isomer, isonicotinic acid, was
      devoid of activity in these two models. In conclusion, our results represent the
      first demonstration of the activity of nicotinic acid in experimental models of
      nociceptive and inflammatory pain and also provide further support to its anti
      inflammatory activity. It is unlikely that conversion to nicotinamide represents
      an important mechanism to explain the antinociceptive and anti-inflammatory
      activities of nicotinic acid. The demonstration of new activities of nicotinic
      acid, a drug that has already been approved for clinical use and presents a
      positive safety record, may contribute to raise the interest in conducting
      clinical trials to investigate its usefulness in the treatment of painful and
      inflammatory diseases.

PMID- 22366214
TI  - Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and
      neuropathic pain models and possible mechanism with allopregnanolone.
AB  - Crude alkaloidal extraction from Gelsemium elegans Benth. produces analgesic
      property. However, its clinical utility has been obstructed by its narrow
      therapeutic index. Here, we investigated the potential of koumine, a monomer of
      Gelsemium alkaloids, to reduce both inflammatory and neuropathic pain.
      Interestingly, allopregnanolone, a neurosteroid, appeared to mediate the
      reduction of neuropathic pain. The potential anti-inflammatory pain effects of
      koumine were evaluated by acetic acid-, formalin- and complete Freund's adjuvant
      (CFA) -induced nociceptive behaviors in mice. Chronic constriction injury (CCI)
      and L5 spinal nerve ligation (L5 SNL), inducing thermal hyperalgesia and
      mechanical allodynia in rats, were used to test whether repeated treatment of
      koumine ameliorated neuropathic pain. Finally, we explored if koumine altered the
      level of neurosteroids in rat spinal cord of CCI neuropathy using liquid
      chromatography-tandem mass spectrometry. Koumine dose-dependently reduced the
      acetic acid-induced writhes and formalin-induced licking/biting time of Phase II
      in mice. Repeated administrations of koumine also dose-dependently reversed the
      CFA-, CCI- and L5 SNL-induced thermal hyperalgesia, as well as, CCI- and L5 SNL
      induced mechanical allodynia in rats. The level of allopregnanolone, but not
      pregnenolone, in the L5-6 spinal cord was elevated by repeated treatment of
      koumine in CCI-induced neuropathic rats. These results demonstrate that koumine
      has a significant analgesic effect in rodent behavioral models of inflammatory
      and neuropathic pain, and that the reduction in neuropathic pain may be
      associated with the upregulation of allopregnanolone in the spinal cord.

PMID- 22366215
TI  - Olfactory sensitivity for "green odors" (aliphatic C(6) alcohols and C(6)
      aldehydes)--a comparative study in male CD-1 mice (Mus musculus) and female
      spider monkeys (Ateles geoffroyi).
AB  - Using a conditioning paradigm, the olfactory sensitivity of six male CD-1 mice
      for "green odors", a group of eight structurally related aliphatic C(6) alcohols
      and aldehydes known to exert anxiolytic and stress-reducing effects, was
      investigated. With all eight stimuli, the animals discriminated concentrations
      <=0.03 ppm (parts per million) from the solvent, and with three of the eight
      stimuli the best-scoring animals were even able to detect concentrations <=0.03
      ppb (parts per billion). Three female spider monkeys tested in parallel were
      found to detect the same eight stimuli at concentrations <1 ppm, and with six of
      the eight stimuli the best-scoring animals detected concentrations <=0.1 ppm.
      Analysis of odor structure-activity relationships showed that in both species the
      type of functional group attached to the aliphatic C(6) backbone of the odorant
      molecules systematically affected their olfactory sensitivity whereas the
      presence/absence of a double bond did not. In the mice, but not in the spider
      monkeys, the position of a double bond and the cis/trans-configuration of the
      odorant molecules also had a systematic effect on detectability of the "green
      odors". A comparison of the detection thresholds between the two species tested
      here and those obtained in human subjects suggests that the number of functional
      olfactory receptor genes is a poor predictor of a species' olfactory sensitivity
      for "green odors".

PMID- 22366216
TI  - Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens
      shell on food-reinforced lever pressing by undeprived rats.
AB  - Previous studies have shown that large increases in food intake in nondeprived
      animals can be induced by injections of both the GABA(A) agonist muscimol and the
      MU-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while
      injections of the catecholamine agonist amphetamine have little effect. In the
      current study we examined whether injections of these drugs are able to increase
      food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained
      to lever press on a continuous reinforcement schedule while food deprived and
      were then tested after being placed back on ad libitum feeding. Under these
      conditions, responding was markedly increased by injections of either muscimol or
      DAMGO, although the onset of the effects of the latter drug was delayed by 30-40
      min. In contrast, amphetamine injections failed to increase reinforced lever
      pressing, although they did enhance responding on a non-reinforced lever,
      presumably reflecting alterations in behavioral activation. These results
      demonstrate that stimulation of GABA(A) and MU-opioid receptors within the AcbSh
      is able to promote not only food intake, but also food-directed operant behavior.
      In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral
      arousal, but does not appear to specifically potentiate behaviors directed toward
      food procurement.

PMID- 22366217
TI  - The combined predictive capacity of rat models of algogen-induced and neuropathic
      hypersensitivity to clinically used analgesics varies with nociceptive endpoint
      and consideration of locomotor function.
AB  - Different neurobiological mechanism(s) might contribute to evoked and non-evoked
      pains and to limited translational drug discovery efforts. Other variables
      including the pain model and sensory testing method used,
      dose/route/preadministration time of compound(s), lack of adverse effect
      profiling and level of observer experience might also contribute. With these
      points in mind, we tested three mechanistically distinct analgesics in rat models
      of algogen-induced and neuropathic pain. In chronic constriction injury (CCI)
      rats evoked hindpaw mechanical hypersensitivity and spontaneous weight bearing
      deficits developed quickly and persisted for at least 3 weeks post-injury. In
      contrast, evoked cold hypersensitivity, or movement-associated behavioural
      deficits (rotarod, beam-walking) were less manifested or dissipated rapidly post
      injury. Mechanical hypersensitivity was dose-dependently reversed by morphine (3
      10 mg/kg, s.c.) and gabapentin (50-200 mg/kg, i.p.). Weight bearing deficits and
      cold hypersensitivity were reversed only by high doses of each drug.
      Surprisingly, duloxetine (10-60 mg/kg, s.c.) was largely ineffective in
      neuropathic rats although it partially reduced formalin-induced spontaneous
      nocifensive behaviours; especially during interphase, a period associated with
      activation of descending monoaminergic inhibition. Morphine and gabapentin
      markedly attenuated second phase formalin- and in addition capsaicin-induced
      nocifensive behaviours; indicative of effects on central sensitization and
      nociceptor hyperexcitability mechanisms. Only gabapentin consistently attenuated
      nociceptive behaviours at a dose that did not impair exploratory locomotor
      behaviour in naive rats. Accordingly, this comparative analysis indicates that
      the pharmacological sensitivity of evoked and non-evoked pain indices does not
      necessarily correlate within models, perhaps reflecting differing underlying
      mechanisms. Conversely, the pharmacological specificity of non-evoked pain
      indices to selected drugs was conserved across models indicative of similar
      underlying mechanisms enduring in the face of differing aetiology. Finally,
      although the predictive capacity of these models was largely unaffected by
      observer-related experience, it was putatively compromised when adverse event
      profiling of each drug was considered in parallel.

PMID- 22366218
TI  - Ethanol exposure during either adolescence or adulthood alters the rewarding
      effects of cocaine in adult rats.
AB  - OBJECTIVES: The present studies assessed the effects of adolescent and adult
      ethanol exposure on the rewarding effects of cocaine as measured with the
      conditioned place preference procedure. METHODS: Male rats were exposed to
      intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days
      (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND
      65 or PND 105, respectively, and consisted of a baseline test followed by four
      conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the
      fourth conditioning cycle a final preference test was performed. Changes in time
      on the drug-paired side between the baseline and final test were analyzed.
      RESULTS: Animals exposed to vehicle (during adolescence or adulthood) showed a
      significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol
      (during adolescence or adulthood) showed a significant place preference at
      10mg/kg cocaine. CONCLUSIONS: Exposure to ethanol (adolescents or adults)
      sensitized the rewarding effects of cocaine. This may indicate an increase in the
      abuse liability of cocaine following a history of ethanol exposure.

PMID- 22366219
TI  - Akebia saponin D attenuates ibotenic acid-induced cognitive deficits and pro
      apoptotic response in rats: involvement of MAPK signal pathway.
AB  - Cholinergic deficit is one of the most remarkable symptoms and plays an important
      role in Alzheimer's disease. In the present study, the protective effects of
      Akebia saponin D (ASD) on learning and memory impairments induced by excitatory
      neurotoxin ibotenic acid injection were examined in vivo. Our findings suggest
      that ASD (90 mg/kg, p.o.) would exert a rescue effect on rats both in behavioral
      performances in Morris water maze and Y maze and cholinergic functions detected
      by chemical methods. We further investigated in the hippocampus and found ASD
      could regulate apoptosis-related proteins expression following ibotenic acid
      injection. Additionally, mitogen-activated protein kinase (MAPK) family
      phosphorylations were inhibited after ASD treatment, implicating that the MAPK
      signaling pathway could be involved in the mechanism underlying neuroprotection
      of ASD against ibotenic acid-induced excitotoxicity.

PMID- 22366220
TI  - Protection by an antioxidant of rotenone-induced neuromotor decline, reactive
      oxygen species generation and cellular stress in mouse brain.
AB  - Exposure to environmental toxins, including rotenone, results in central nervous
      system and systemic toxicity. Rotenone is a widely used pesticide and a
      mitochondrial complex I (CI) inhibitor. This study reports effectiveness of a
      synthetic lipoylcarnitine antioxidant compound, lipoylcarnitine methyl ester
      iodide (PMX-500F), for treatment of chronic rotenone induced neurological
      deficits in mice. Mice (C57BL/6NTac; two months of age) received oral
      administration of rotenone (30 mg/kg/day) or vehicle, preceded by intraperitoneal
      injection of PMX-500F (19 mg/kg) or vehicle for four weeks. In the Rota-rod test,
      rotenone treatment had no effect (P>0.05); however, PMX-500F treatment improved
      locomotor coordination and endurance (latency to fall time; P<0.05). For
      neuromuscular strength (wire hang test), rotenone treated mice showed reduced
      latency to fall compared to control mice (P<0.05). PMX-500F treatment improved
      the outcome in both control and rotenone exposed mice (P<0.05). Rotenone
      administration increased ROS generation in the forebrain and midbrain regions,
      but not in the cerebellum (P<0.05). Co-treatment with PMX-500F normalized the ROS
      in forebrain and midbrain regions to that of the control concentrations. In
      rotenone administered mice, activated stress-activated protein kinase/c-Jun NH2
      terminal kinase (pSAPK/JNK) was higher in forebrain and midbrain lysates than in
      control mice (P<0.05) and treatment with PMX-500F reduced pSAPK/JNK to control
      levels. The pSAPK/JNK levels in the cerebellum were similar in all four groups
      (P>0.05). Total SAPK/JNK was not altered by either rotenone or PMX-500F treatment
      (P>0.05). These results illustrate that an antioxidant, here PMX-500F, provides
      protection against rotenone induced decline in neuromotor function, reactive
      oxygen species (ROS) generation and cellular stress.

PMID- 22366221
TI  - Microarray analysis of the global gene expression profile following hypothermia
      and transient focal cerebral ischemia.
AB  - BACKGROUND: Hypothermia is one of the most robust experimental neuroprotective
      interventions against cerebral ischemia. Identification of molecular pathways and
      gene networks together with single genes or gene families that are significantly
      associated with neuroprotection might help unravel the mechanisms of therapeutic
      hypothermia. MATERIAL AND METHODS: We performed a microarray analysis of ischemic
      rat brains that underwent 90 min of middle cerebral artery occlusion (MCAO) and
      48 h of reperfusion. Hypothermia was induced for 4 h, starting 1 h after MCAO in
      male Wistar rats. At 48 h, magnetic resonance imaging (MRI) was performed for
      infarct volumetry, and functional outcome was determined by a neuroscore. The
      brain gene expression profile of sham (S), ischemia (I), and ischemia plus
      hypothermia (HI) treatment were compared by analyzing changes of individual
      genes, pathways, and networks. Real-time reverse-transcribed polymerase chain
      reaction (RT-PCR) was performed on selected genes to validate the data. RESULTS:
      Rats treated with HI had significantly reduced infarct volumes and improved
      neuroscores at 48 h compared with I. Of 4067 genes present on the array chip, HI
      compared with I upregulated 50 (1.23%) genes and downregulated 103 (3.20%) genes
      equal or greater than twofold. New genes potentially mediating neuroprotection by
      hypothermia were HNRNPAB, HIG-1, and JAK3. On the pathway level, HI globally
      suppressed the ischemia-driven gene response. Twelve gene networks were
      identified to be significantly altered by HI compared with I. The most
      significantly altered network contained genes participating in apoptosis
      suppression. CONCLUSIONS: Our data suggest that although hypothermia at the
      pathway level restored gene expression to sham levels, it selectively regulated
      the expression of several genes implicated in protein synthesis and folding,
      calcium homeostasis, cellular and synaptic integrity, inflammation, cell death,
      and apoptosis.

PMID- 22366222
TI  - Enhanced neurogenesis in organotypic cultures of rat hippocampus after transient
      subfield-selective excitotoxic insult induced by domoic acid.
AB  - New neurons are continuously generated in the hippocampus and may play an
      important role in many physiological and pathological conditions. Here we present
      evidence of cell proliferation and neurogenesis after a selective and transient
      excitotoxic injury to the hippocampal cornu ammonis 1 (CA1) area induced by low
      concentrations of domoic acid (DOM) in rat organotypic hippocampal slice cultures
      (OHSC). DOM is an excitatory amino acid analog to kainic acid that acts through
      glutamate receptors to elicit a rapid and potent excitotoxic response. Exposure
      of slice cultures to varying concentrations of DOM for 24 h induced dose
      dependent neuronal toxicity that was independent of activation of classic
      apoptotic markers. Treatment with 2 MUM DOM for 24 h caused a selective yet
      transient neurotoxic injury in the CA1 subfield of the hippocampus that appeared
      recovered after 7 days of incubation in a DOM-free medium and showed significant
      microgliosis but no sign of astrogliosis. The DOM insult (2 MUM, 24 h) resulted
      in a significant upregulation of cell proliferation, as assessed by 5-bromo-2
      deoxyuridine (BrdU) incorporation, and a concurrent increase of the neuronal
      precursor cell marker doublecortin (DCX) within the subgranular zone of the
      dentate gyrus and area CA1. Neurogenesis occurred primarily during the first week
      after termination of the DOM exposure. Our study shows that exposure of OHSC to
      concentrations of DOM below those required to induce permanent neurotoxicity can
      induce proliferation and differentiation of neural progenitor cells that may
      contribute to recovery from mild injury and to develop abnormal circuits relevant
      to disease.

PMID- 22366223
TI  - Engineered silica nanocarriers as a high-payload delivery vehicle for antioxidant
      enzymes.
AB  - Antioxidant enzymes for the treatment of oxidative stress-related diseases remain
      a highly promising therapeutic approach. As poor localization and stability have
      been the greatest challenges to their clinical translation, a variety of
      nanocarrier systems have been developed to directly address these limitations. In
      most cases, there has been a trade-off between the delivered mass of enzyme
      loaded and the carrier's ability to protect the enzyme from proteolytic
      degradation. One potential method of overcoming this limitation is the use of
      ordered mesoporous silica materials as potential antioxidant enzyme nanocarriers.
      The present study compared the loading, activity and retention activity of an
      anti-oxidant enzyme, catalase, on four engineered mesoporous silica types: non
      porous silica particles, spherical silica particles with radially oriented pores
      and hollow spherical silica particles with pores oriented either parallel to the
      hollow core or expanded, interconnected bimodal pores. All these silica types,
      except non-porous silica, displayed potential for effective catalase loading and
      protection against the proteolytic enzyme, pronase. Hollow particles with
      interconnected pores exhibit protein loading of up to 50 wt.% carrier mass, while
      still maintaining significant protection against proteolysis.

PMID- 22366224
TI  - An ERP study of the interaction between verbal information and conditioning
      pathways to fear.
AB  - Two experiments are described that explore the effects of verbal information and
      direct conditioning in the acquisition and extinction of fear responses.
      Participants were given verbal threat information about novel animals before
      conditioning trials in which the animals were presented alongside an aversive
      outcome (Experiment 1), or positive information about the animals before
      extinction trials (Experiment 2). Fear was measured using self-reported fear
      beliefs, expectancy of the unconditioned stimulus (US) and event-related brain
      potential (ERP). The results showed a direct effect of verbal information on
      acquisition (Experiment 1) and extinction (Experiment 2). There was a P2 peak
      latency shift at acquisition (Experiment 1) and P1 mean amplitude response at
      extinction (Experiment 2) based on the interaction between verbal information and
      US-contingency. However, the P2 response showed little evidence for an enhanced
      conditioned response (CR) when verbal threat information and direct conditioning
      combined: earlier P2 responses were found for all animals that had been
      associated with either threat information or the aversive US. Additionally,
      increase in P1 mean amplitude response (Experiment 2) seemed to stem from the
      conflict between verbal information and contingency information, rather than the
      predicted decrease in response where positive information and extinction training
      were combined. Future studies are suggested that might explore whether
      attention/arousal modulate the P1 response as a result of such expectation
      violations.

PMID- 22366227
TI  - Effects of ultrasound on the synthesis of silicalite-1 nanocrystals.
AB  - Application of power ultrasound, offers potential in the degree of control over
      the preparation and properties of nanocrystalline zeolites, which have become
      increasingly important due to their diverse emerging applications. Synthesis of
      silicalite-1 nanocrystals from a clear solution was carried out at 348 K in the
      absence and presence of ultrasound of 300 and 600 W, in an attempt to investigate
      the effects of sonication, in this respect. Variation of the particle size and
      particle size distribution was followed with respect to time using a laser light
      scattering device with a detector set to collect back-scattered light at an angle
      of 173 degrees . Product yield was determined and the crystallinity was analyzed
      by X-ray diffraction for selected samples collected during the syntheses.
      Nucleation, particle growth and crystallization rates all increased as a result
      of the application of ultrasound and highly crystalline silicalite-1 of smaller
      average particle diameter could be obtained at shorter synthesis times. The
      particle size distributions of the product populations, however, remained similar
      for similar average particle sizes. The rate of increase in yield was also
      speeded up in the presence of ultrasound, while the final product yield was not
      affected. Increasing the power of ultrasound, from 300 to 600 W, increased the
      particle growth rate and the crystalline domain size, and decreased both the
      final particle diameter and the time required for the particle growth to reach
      completion, while its effect on nucleation was unclear.

PMID- 22366225
TI  - Neural correlates of source memory retrieval in young, middle-aged and elderly
      adults.
AB  - Event-related potentials (ERPs) were recorded in young (21-27 years old), middle
      aged (50-57 years old) and older adults (70-77 years old) to determine whether
      the decline in source memory that occurs with advancing age coincides with
      contemporaneous neurophysiological changes. Source memory for the spatial
      location (quadrant on the screen) of images presented during encoding was
      examined. The images were shown in the center of the screen during the retrieval
      task. Retrieval success for source information was characterized by different
      scalp topographies at frontal electrode sites in young adults relative to middle
      aged and older adults. The right frontal effect during unsuccessful retrieval
      attempts showed amplitude and latency differences across age groups and was
      related to the ability to discriminate between old and new images only in young
      adults. These results suggest that the neural correlates of the retrieval success
      and attempt were affected by age and these effects were present by middle-age.

PMID- 22366228
TI  - Impact of ultrasonic pretreatment under different operational conditions on the
      mesophilic anaerobic digestion of sunflower oil cake in batch mode.
AB  - In this study ultrasonic (US) pretreatment was investigated with the aim of
      improving the anaerobic digestion of sunflower oil cake (SuOC), the solid waste
      derived from the extraction process of sunflower oil. Five ultrasonic
      pretreatment assays were conducted at specific energy (SE) and sonication times
      in a range from 24,000 kJ/kg TS and 16.6 min (assay 1: US1) to 597,600 kJ/kg TS
      and 331.2 min (assay 5: US5), respectively, all operating at a constant
      sonication frequency (20 kHz) and ultrasonic power (120 W). As regards ultrasonic
      pretreatment, the working conditions of the first assay (US1) using samples of
      SuOC at 2% (w/v) showed to be the most appropriate in terms of both lignin and
      hemicellulose degradation (57.7% and 66.7%, respectively) and cellulose increase
      (54% increase with respect to its initial concentration). The percentage of COD
      solubilization increased from only 14% to 21% when SE was 25 times higher.
      Results obtained in batch anaerobic digestion experiments (biochemical methane
      potential - BMP - tests) conducted at 35 degrees C of the solid and liquid
      fractions released from the different ultrasonic conditions tested, indicated
      that for the first experiment (US1) the average ultimate methane yield obtained
      was 53.8% higher than that achieved for untreated SuOC. Finally, the kinetic
      constants of the anaerobic digestion of the solid and liquid fractions released
      after the ultrasonic pretreatment were virtually independent of the operation
      conditions assayed.

PMID- 22366229
TI  - Simple sonochemical synthesis and characterization of HgSe nanoparticles.
AB  - Mercury selenide (HgSe) nanostructures were synthesized via a sonochemical method
      based on the reaction between HgCl(2), SeCl(4) and hydrazine hydrate
      (N(2)H(4).H(2)O) in water, in presence of various capping agents. The effects of
      preparation parameters such as: the kind of capping agent and its amount,
      ultrasonic power, reaction time and temperature were investigated. It was found
      that morphology, particle size and phase of the products could be greatly
      affected by these parameters. HgSe nanostructures were characterized by X-ray
      powder diffraction (XRD), transmission electron microscopy (TEM), scanning
      electron microscopy (SEM), photoluminescence spectroscopy (PL) and X-ray energy
      dispersive spectroscopy (EDS).

PMID- 22366230
TI  - Fluorogen activating proteins in flow cytometry for the study of surface
      molecules and receptors.
AB  - The use of fluorescent proteins, particularly when genetically fused to proteins
      of biological interest, have greatly advanced many flow cytometry research
      applications. However, there remains a major limitation to this methodology in
      that only total cellular fluorescence is measured. Commonly used fluorescent
      proteins (e.g., EGFP and its variants) are fluorescent whether the fusion protein
      exists on the surface or in sub-cellular compartments. A flow cytometer cannot
      distinguish between these separate sources of fluorescence. This can be of great
      concern when using flow cytometry, plate readers or microscopy to quantify cell
      surface receptors or other surface proteins genetically fused to fluorescent
      proteins. Recently developed fluorogen activating proteins (FAPs) solve many of
      these issues by allowing the selective visualization of only those cell surface
      proteins that are exposed to the extracellular milieu. FAPs are GFP-sized single
      chain antibodies that specifically bind to and generate fluorescence from
      otherwise non-fluorescent dyes ('activate the fluorogen'). Like the fluorescent
      proteins, FAPs can be genetically fused to proteins of interest. When exogenously
      added fluorogens bind FAPs, fluorescence immediately increases by as much as
      20,000-fold, rendering the FAP fusion proteins highly fluorescent. Moreover,
      since fluorogens can be made membrane impermeant, fluorescence can be limited to
      only those receptors expressed on the cell surface. Using cells expressing beta-2
      adrenergic receptor (beta2AR) fused at its N-terminus to a FAP, flow cytometry
      based receptor internalization assays have been developed and characterized. The
      fluorogen/FAP system is ideally suited to the study of cell surface proteins by
      fluorescence and avoids drawbacks of using receptor/fluorescent protein fusions,
      such as internal accumulation. We also briefly comment on extending FAP-based
      technologies to the study of events occurring inside of the cell as well.

PMID- 22366232
TI  - Insights into the anomalous heme pocket of rainbow trout myoglobin.
AB  - Rainbow trout myoglobin (Mb) is characterized by an unusually low affinity for
      oxygen, having a P(50) of 4.92+/-0.29 mm Hg at 25  degrees C which is the highest
      ever reported for any vertebrate Mb at the same temperature (Helbo and Fago,
      (2011) Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R101-R108). In order to
      gain insight into the structural factors of the heme pocket that may be important
      determinants for this atypical oxygen affinity, we have carried out an electronic
      absorption and resonance Raman characterization of the ferric and ferrous protein
      with and without exogenous ligands (O(2), CO, F(-)) and compared the results with
      those of other Mbs. While the nu(Fe-His) stretch appears at a frequency similar
      to other vertebrate Mbs, the resonance Raman frequencies of the Fe-ligand
      stretching modes reveal significant variations in the interaction of iron-bound
      ligands with distal residues. In particular, the spectroscopic characterization
      highlights two exceptional properties of rainbow trout Mb, a significantly higher
      level of reversed heme and reduced hydrogen bonding interactions between ligands
      and the distal HisE7 residue compared with other Mbs. The weakening of the
      hydrogen bond interaction is proposed to be the primary cause of the
      significantly reduced oxygen affinity.

PMID- 22366231
TI  - Comparative studies on manganese-based SOD mimetics, including the phosphate
      effect, by using global spectral analysis.
AB  - Stopped-flow measurements have been successfully combined with time-resolved
      UV/vis spectroscopy and global spectral analysis of superoxide decay for the
      comparative study of catalytic activity of putative manganese SOD (superoxide
      dismutase) mimetics known in the literature. The SOD activity of the studied
      complexes decreases in the following order: a) M40403>Mn(III)TM-4
      PyP(5+)>Mn(II)pyane >>EUK-113 at pH 7.4
      (M40403=([manganese(II)dichlorido{(4R,9R,14R,19R)-3,10,13,20,26
      pentaazatetracyclo[20.3.1.0.4,9014,19]hexacosa-1(26),-22(23),24-triene}],
      Mn(III)TM-4-PyP(5+)=Mn(III)meso-tetrakis(N-methylpyridinium-4-yl)porphyrin,
      Mn(II)Pyane=Mn(II)trans-2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]
      octadeca-1(18),14,16-triene, EUK-113=[manganese(III)acetato(6,6'-((1E,1'E)
      (ethane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenolate)])
      in Hepes buffer (Hepes=4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid), b)
      Mn(III)TM-4-PyP(5+)>M40403?Mn(II)pyane >>EUK-113 at pH 8.1 in Hepes buffer and c)
      Mn(III)TM-4-PyP(5+)?Mn(II)pyane>MnCl(2)>M40403?EUK-113 at pH 7.4 in phosphate
      buffer. MnCl(2) in Hepes, Mn(III)TSPP(3-), Mn(III)TBAP(3-), Mn(III)acetate,
      Mn(II)lactate and Mn(II)EDTA do not exhibit SOD activity (Mn(III)TSPP(3
      )=Mn(III)mesotetrakis(benzoic acid)porphyrin, Mn(III)TBAP(3
      )=Mn(III)mesotetrakis(4-sulfonatophenyl)porphyrin). MnCl(2) possess SOD activity
      that is comparable with those of other mimetics in the presence of phosphate. Our
      results demonstrate that phosphate anions, independent of ionic strength effect,
      influence the activity of manganese SOD mimetics, which is crucial for
      understanding and comparing their biological activity.

PMID- 22366235
TI  - Chronic obstructive pulmonary disease: a slowly progressive cardiovascular
      disease masked by its pulmonary effects?

PMID- 22366233
TI  - Selenate enhances STAT3 transcriptional activity in endothelial cells:
      differential actions of selenate and selenite on LIF cytokine signaling and cell
      viability.
AB  - Sodium selenate may have utility in treating Alzheimer's disease and diabetes;
      however, its impact on the associated proinflammatory cytokine signaling of
      endothelial cells has not been investigated. We report that treatment of human
      microvascular endothelial cells with sodium selenate at a pharmacological dose
      (100 MUM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response
      to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced
      STAT3 activity. Accordingly, STAT3 nuclear binding to DNA was increased, as well
      as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). CCL2
      plays a key role in inflammatory processes associated with neuronal degenerative
      and vascular diseases. The enhancing action of selenate on LIF-induced STAT3 Y705
      phosphorylation was replicated by vanadate and a specific inhibitor of protein
      tyrosine phosphatase, non-receptor type 1 (PTP1B). Moreover, we observed that
      selenite, the cellular reduction bioproduct of selenate but not selenate itself,
      inhibited enzymatic activity of human recombinant PTP1B. Our findings support the
      conclusion that in human microvascular endothelial cells selenate has a vanadate
      like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation.
      These findings raise the possibility that beneficial actions of supranutritional
      levels of selenate for treating Alzheimer's and diabetes may be offset by a
      proinflammatory action on endothelial cells.

PMID- 22366234
TI  - Airflow obstruction, lung function, and risk of incident heart failure: the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - AIMS: We examined the relationship between forced expiratory volume in 1 s
      (FEV(1)), airflow obstruction, and incident heart failure (HF) in black and
      white, middle-aged men and women in four US communities. METHODS AND RESULTS:
      Lung volumes by standardized spirometry and information on covariates were
      collected on 15 792 Atherosclerosis Risk in Communities (ARIC) cohort
      participants in 1987-89. Incident HF was ascertained from hospital records and
      death certificates up to 2005 in 13 660 eligible participants. Over an average
      follow-up of 14.9 years, 1369 (10%) participants developed new-onset HF. The age-
      and height-adjusted hazard ratios (HRs) for HF increased monotonically over
      descending quartiles of FEV(1) for both genders, race groups, and smoking status.
      After multivariable adjustment for traditional cardiovascular risk factors and
      height, the HRs [95% confidence intervals (CIs)] of HF comparing the lowest with
      the highest quartile of FEV(1) were 3.91 (2.40-6.35) for white women, 3.03 (2.12
      4.33) for white men, 2.11 (1.33-3.34) for black women, and 2.23 (1.37-3.59) for
      black men. The association weakened but remained statistically significant after
      additional adjustment for systemic markers of inflammation. The multivariable
      adjusted incidence of HF was higher in those with FEV(1)/forced vital capacity
      <70% vs. >=70%: HR 1.44 (95% CI 1.20-1.74) among men and 1.40 (1.13-1.72) among
      women. A consistent and positive association with HF was seen for self-reported
      diagnosis of emphysema and chronic obstructive pulmonary disease, but not for
      asthma. CONCLUSIONS: In this large population-based cohort with long-term follow
      up, low FEV(1) and an obstructive respiratory disease were strongly and
      independently associated with the risk of incident HF.

PMID- 22366236
TI  - Selenium and/or iodine deficiency alters hepatic xenobiotic metabolizing enzyme
      activities in rats.
AB  - The objective of this study was to investigate the effects of iodine (I(2))
      and/or selenium (Se) deficiency on thyroid hormones and hepatic xenobiotic
      metabolizing enzyme systems using a triple animal model. Three-week-old male
      Wistar rats were fed for seven weeks. Se deficiency was introduced by a diet
      containing <0.005 mg/kg Se, and I(2) deficiency was produced by sodium
      perchlorate containing drinking water. The levels of plasma thyroid hormones
      [total T(4) (TT(4)), total T(3) (TT(3))], thyroid stimulating hormone (TSH);
      total microsomal cytochrome P450 (CYP450) and cytochrome b5 (CYP b5) levels;
      activities of microsomal NADPH-cytochrome P450 reductase (P450R), microsomal
      aniline hydroxylase (CYP2E1), microsomal 7-ethoxyresorufin O-deethylase (EROD),
      microsomal 7-pentoxyresorufin O-depentylase (PROD) and cytosolic glutathione S
      transferase (GST) were determined. In I(2) deficiency total CYP450 levels,
      activities of CYP2E1, EROD and GST decreased, and CYP b5 content increased
      significantly. In Se-deficient rats, total CYP450 level and CYP2E1 activity
      increased, and EROD and GST activities and CYP b5 level decreased significantly.
      In combined I(2) and Se deficiency, except for CYP450 content and CYP2E1
      activity, all enzyme activities and CYP b5 content decreased significantly
      compared to control group. Overall results of this study have suggested that
      metabolism of xenobiotics as well as endogenous compounds is affected by Se and
      I(2) status.

PMID- 22366237
TI  - Nickel species: analysis and toxic effects.
AB  - This review gives an overview on the analysis of inorganic nickel species and
      their toxic effects. Based on the analytical procedure applied inorganic nickel
      species are usually classified in soluble, sulfidic, metallic and oxidic nickel
      fractions. Only few works were attempting a chemical characterization of the
      different nickel compounds in each fraction. This general classification in four
      nickel species groups is widely used in toxicological studies dealing with nickel
      particulate matter in workplace air. Compared to the general population,
      occupationally exposed people have a higher risk of respiratory tract cancer due
      to inhalation of nickel at their workplace in the nickel-producing or using
      industries. High cancer risk is related to less soluble oxidic and especially
      sulfidic nickel species in refinery dust. In contrast, within the general
      population the most harmful health effect related to nickel exposure is allergic
      contact dermatitis due to prolonged skin contact with nickel. Absorption
      processes of nickel species and molecular mechanisms of nickel toxicity are
      briefly outlined.

PMID- 22366238
TI  - Do symptoms of sluggish cognitive tempo in children with ADHD symptoms represent
      comorbid internalizing difficulties?
AB  - OBJECTIVE: Symptoms of sluggish cognitive tempo (SCT) are correlated with
      inattention and internalizing difficulties. The purpose of the present study was
      to determine whether symptoms of SCT reflect comorbid internalizing disorder with
      ADHD or a separate syndrome. METHOD: Using a clinical sample of youth evaluated
      for behavioral and learning difficulties (N = 73), this study examined whether
      SCT remains associated with symptoms of ADHD after accounting for comorbid
      symptoms of anxiety and depression reported by children and parents. RESULTS: SCT
      symptoms were correlated with inattention and parent reports of child depression,
      but not with parent-reported anxiety or child reports of internalizing problems.
      Inattention (in the absence of hyperactivity/impulsivity) remained uniquely
      associated with SCT even after accounting for internalizing problems. CONCLUSION:
      The findings confirm SCT as a correlate of inattention and support its construct
      validity as separate from comorbid internalizing problems. Further research on
      the clinical utility of SCT is needed.

PMID- 22366239
TI  - ADHD medication vacations and parent-child interactions by gender.
AB  - OBJECTIVE: The purpose of the current study was to examine medication vacations
      among children with ADHD according to parent-child dyads (e.g., mother-son,
      father-daughter, mother-daughter, and father-son). METHOD: In a survey study of
      259 parents of children with ADHD, the use of medication vacations according to
      parent-child sex dyads was examined. RESULTS: Results of the current study
      suggest that fathers seem to report endorsing medication vacations more with
      their sons with ADHD as opposed to their daughters with ADHD. There did not seem
      to be any significant differences among mothers. CONCLUSION: Results of the
      current study conclude with directions for future research and practice.

PMID- 22366240
TI  - Efficacy of atomoxetine for the treatment of ADHD symptoms in patients with
      pervasive developmental disorders: a prospective, open-label study.
AB  - OBJECTIVE: Atomoxetine's tolerance and efficacy were studied in 24 patients with
      pervasive developmental disorder and symptoms of ADHD. METHOD: Prospective, open
      label, 16-week study was performed, using the variables of the Clinical Global
      Impression Scale and the Conners' Scale, among others. RESULTS: A significant
      difference was found between pre- and posttreatment scores as well as a
      significant reduction was found on the scales used. Only five patients presented
      adverse events. CONCLUSION: Atomoxetine therefore appears to be a useful drug,
      pointing to the need for larger, randomized, controlled, double-blind studies to
      confirm its efficacy versus placebo and in comparison with other treatment
      options.

PMID- 22366241
TI  - An infant with spinal muscular atrophy and tetrology of Fallot.

PMID- 22366242
TI  - Polyglandular autoimmune syndrome type 4 with GAD antibody and dystonia.

PMID- 22366243
TI  - Accurate estimation of motor symptoms by diffusion tensor imaging in a patient
      with advanced Moyamoya disease.

PMID- 22366244
TI  - Neuro-Sweet disease mimicking recurrent anaplastic astrocytoma associated with
      therapy-related myelodysplastic syndrome: a case report.

PMID- 22366245
TI  - Diaphragm paralysis caused by transverse cervical artery compression of the
      phrenic nerve: the Red Cross syndrome.
AB  - BACKGROUND: The etiology of diaphragm paralysis is often elusive unless an
      iatrogenic or traumatic injury to the phrenic nerve can be clearly implicated.
      Until recently, there has been little interest in the pathophysiology of
      diaphragm paralysis since few treatment options existed. METHODS: We present
      three cases of symptomatic diaphragm paralysis in which a clear clinico
      pathologic diagnosis could be identified, specifically a vascular compression of
      the phrenic nerve in the neck caused by a tortuous or adherent transverse
      cervical artery. RESULTS: In two patients the vascular compression followed a
      preceding traction injury, whereas in one patient an inter-scalene nerve block
      had been performed. Following vascular decompression, all three patients regained
      diaphragmatic motion on fluoroscopic chest radiographs, and experienced a
      resolution of respiratory symptoms. CONCLUSION: We suggest that vascular
      compression of the phrenic nerve in the neck may occur following traumatic or
      iatrogenic injuries, and result in symptomatic diaphragm paralysis.

PMID- 22366246
TI  - Usefulness of estimating the volume gained by decompressive craniectomy.

PMID- 22366247
TI  - Synergistic effect of PKC activation and actin filament disruption on carbonate
      apatite-facilitated lymphocyte transfection.
AB  - Leukemia and lymphoma cells are potential targets for genetic manipulation in
      cancer therapy. On the other hand, genetically modified autologous lymphocytes
      expressing a chimeric antigen against a receptor overexpressed in tumor cells or
      tumor vasculature are promising cell-based therapeutics for cancer.However, the
      lack of a smart device for efficient transgene delivery to the lymphocytes poses
      the major obstacle to the successful clinical applications of these attractive
      approaches. Recently, we developed a carbonate apatite-based nanocarrier system
      for effective intracellular delivery and release of DNA molecules, achieving very
      high level of transgene expression in both primary and cancer cells. Although its
      efficacy in human T leukemia cells is relatively poor, immobilization of
      fibronectin and/or chimeric E-cadherin-Fc on particle surface could enhance
      transgene delivery in presence of an actin filament disrupter. Here, we report
      for the first time that simultaneous stimulation of human T leukemia cells by a
      protein kinase C (PKC) activator, a Ca(2+) ionophore and an actin filament
      disrupter dramatically accelerated carbonate apatite-mediated transgene delivery
      in the cells, resulting in over 100-fold more efficacy than commcercially
      available lipofectamine.

PMID- 22366248
TI  - NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing
      hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a
      xenograft mouse model.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer
      agents. However, their long-term use is associated with adverse gastrointestinal
      effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and
      hydrogen sulfide (H(2)S) can increase mucosal defense mechanisms has led to the
      development of NO- and H(2)S-releasing NSAIDs with increased safety profiles.
      Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H(2)S-releasing
      agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC(50)s of 45.5 +/-
      2.5, 19.7 +/- 3.3, and 7.7 +/- 2.2 nM at 24, 48, and 72 h, respectively. This is
      the first NSAID based agent with such high degree of potency. NOSH-aspirin
      inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle
      block. Reconstitution and structure-activity studies representing a fairly close
      approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more
      potent than the sum of its parts towards growth inhibition. NOSH-aspirin
      inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a
      human colon cancer xenograft caused a reduction in volume of 85%. Taken together,
      these results demonstrate that NOSH-aspirin has strong anti-cancer potential and
      merits further evaluation.

PMID- 22366249
TI  - Expression of cuticular protein genes, BmorCPG11 and BMWCP5 is differently
      regulated at the pre-pupal stage in wing discs of Bombyx mori.
AB  - Through BLAST search of the genomic database of Bombyx mori, we found a clone,
      BmorCPG11, which has only putative BR-C binding sites in the 2 kb upstream
      region. Both BmorCPG11 and BR-Z2 were expressed in the cephalic region of the
      epidermis, differently from BR-Z1 and BR-Z4. BR-Z2 transcripts increased by the
      addition of 20-hydroxyl-ecdysone (20E), which was slightly inhibited by
      cycloheximide. BmorCPG11 expression was also induced by the addition of 20E,
      which was inhibited by cycloheximide. Both BmorCPG11 and BR-Z2 were induced by
      the 20E pulse treatment, but they were inhibited by the addition of
      cycloheximide. Both genes showed similar expression pattern in wing discs during
      the developmental stage and in vitro ecdysone responsiveness, and both showed
      relatedness. The result of a reporter assay demonstrated the strong relatedness
      of BmorCPG11 and BR-Z2. The expression profiles of BmorCPG11 and BR-Z2 are
      different from those of BMWCP5 and betaFTZ-F1. The present findings showed
      different regulation of cuticular protein genes by ecdysone-responsive
      transcription factors at the pre-pupal stage of wing discs of B. mori.

PMID- 22366250
TI  - Paracrine regulation of vascular tone, inflammation and insulin sensitivity by
      perivascular adipose tissue.
AB  - A small amount of adipose tissue associated with small arteries and arterioles is
      encountered both in mice and man. This perivascular adipose tissue (PVAT) has a
      paracrine effect on the vascular tone regulation. PVAT is expanded in obesity and
      in diabetes. This expansion not only involves enlargement of fat cells, but also
      the accumulation of inflammatory cells and a shift in the production of
      adipokines and cytokines. This effect is illustrated in this review by the effect
      of PVAT-derived factors of insulin-mediated vasoregulation in mouse resistance
      arteries. Insulin sensitivity of endothelial cells is also involved in the
      insulin-mediated regulation of muscle glucose uptake. Insulin affects
      vasoregulation by acting on different signaling pathways regulating NO and
      endothelin-1 release. This process is influenced by various adipokines and
      inflammatory mediators released from PVAT, and is affected by the degree of
      expansion and content of inflammatory cells. It is modulated by adiponectin (via
      5' adenosine monophosphate-activated protein kinase, AMPK), TNFalpha (via c-jun N
      terminal kinase) and free fatty acids (via protein kinase C-theta). PVAT thus
      provides an important site of control of vascular (dys)function in obesity and
      type 2 diabetes. An altered profile of adipokine and cytokine production by PVAT
      of resistance arteries may also contribute to or modulate hypertension, but a
      causal role in hypertension has still to be established.

PMID- 22366251
TI  - Copy number aberrations in combined hepatocellular carcinoma and
      cholangiocarcinoma.
AB  - Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is a rare liver
      cancer which shares unequivocal features of both hepatocellular carcinoma (HCC)
      and cholangiocarcinoma (CC). A greater awareness of genetic relationship between
      HCC and CC components is limited. To help characterize this rare liver neoplasm,
      we described clinicopathologic features and evaluated copy number (CN) changes in
      this study. A total of 13 cases of CHC were collected. Four paired HCC and CC
      components from four cases were first subject to genome-wide analysis. Nine
      target genes were subsequently selected for further analysis using quantitative
      polymerase chain reaction. The paired HCC and CC components in each case had a
      concordant trend of CN gain or loss in these nine genes. However, the magnitude
      of concordant CN gain or loss was different. There were significant differences
      of CN copies between HCC and CC in each case. We demonstrate genetic divergence
      between HCC and CC components in CHC.

PMID- 22366252
TI  - Reproducibility of cerebral and peripheral haemodynamic responses to active,
      passive and motor imagery paradigms in older healthy volunteers: a fTCD study.
AB  - Cerebral blood flow velocity (CBFv) changes to sensorimotor and cognitive
      paradigms have been used to assess the integrity of haemodynamic responses,
      though the reproducibility of these responses has not been properly assessed.
      Continuous recordings of blood pressure, end-tidal CO(2), heart rate and
      bilateral CBFv were obtained during 60s of active, passive and mental imagined
      paradigms on two different occasions over a 1-week period in 13 healthy subjects.
      The correlation coefficient, standard error of measurement (SEM), intra-class
      correlation (ICC) and its 95% CI (confidence intervals) for each variable were
      calculated at the beginning and end of each paradigm. The temporal patterns of
      haemodynamic responses revealed substantial reproducibility. For the CBFv
      response, the SEM ranged from 2.4 to 5.5% for the different manoeuvres, whilst
      the ICC ranged from 0.5 to 0.8 with better reproducibility occurring at the
      beginning of the paradigm. These findings have important implications for the
      design of studies of the natural history of haemodynamic changes following ageing
      and disease.

PMID- 22366253
TI  - Atypical male and female presentations of FLNA-related periventricular nodular
      heterotopia.
AB  - Periventricular nodular heterotopia, the most common form of cortical
      malformation in adulthood, is characterized by nodules of neurons ectopically
      placed along the lateral ventricles. Classically, ectopic nodules are bilateral
      and symmetric defining bilateral periventricular nodular heterotopia (BPNH). BPNH
      can lead to epilepsy and intellectual disability of variable severity. The X
      linked dominant form of BPNH, related to mutations in FLNA encoding filamin A, is
      the major cause of BPNH, causing prenatal and neonatal lethality in males that
      explain the excess of affected women. However, few living males have been
      described with this condition. In addition, mutations in FLNA have been also
      exceptionally associated with unilateral nodular heterotopia. We describe here
      three new patients, all carrying a novel missense mutation in FLNA. Two of the
      patients were adult males with BPNH; both had normal cognitive development and
      one did not manifest any seizure until he died at age 57. The last patient was a
      female adult with epilepsy and focal nodules essentially located along the right
      ventricle. We compare the clinical and imaging data of our patients with those of
      previously described similar cases. The type and location of FLNA mutations
      leading to such atypical presentations are discussed.

PMID- 22366254
TI  - Effect of exercise-induced fatigue on postural control of the knee.
AB  - Muscle fatigue is associated with reduced power output and work capacity of the
      skeletal muscle. Fatigue-induced impairments in muscle function are believed to
      be a potential cause of increased injury rates during the latter stages of
      athletic competition and often occur during unexpected perturbations. However the
      effect of fatigue on functionally relevant, full body destabilizing perturbations
      has not been investigated. This study examines the effect of muscle fatigue on
      the activation of the quadriceps and hamstrings to fast, full body perturbations
      evoked by a moveable platform. Surface electromyographic (EMG) signals were
      recorded from the knee extensor (vastus medialis, rectus femoris, and vastus
      lateralis) and flexor muscles (biceps femoris and semitendinosus) of the right
      leg in nine healthy men during full body perturbations performed at baseline and
      immediately following high intensity exercise performed on a bicycle ergometer.
      In each condition, participants stood on a moveable platform during which 16
      randomized postural perturbations (eight repetitions of two perturbation types: 8
      cm forward slides, 8 cm backward slides) with varying inter-perturbation time
      intervals were performed over a period of 2-3 min. Maximal voluntary knee
      extension force was measured before and after the high intensity exercise
      protocol to confirm the presence of fatigue. Immediately after exercise, the
      maximal force decreased by 63% and 66% for knee extensors and flexors,
      respectively (P<0.0001). During the post-exercise postural perturbations, the EMG
      average rectified value (ARV) was significantly lower than the baseline condition
      for both the knee extensors (average across all muscles; baseline: 19.7+/
      25.4MUV, post exercise: 16.2+/-19.4 MUV) and flexors (baseline: 24.3+/-20.9 MUV,
      post exercise: 13.8+/-11.0 MUV) (both P<0.05). Moreover the EMG onset was
      significantly delayed for both the knee extensors (baseline: 132.7+/-32.9 ms,
      post exercise: 170.8+/-22.9 ms) and flexors (baseline: 139.1+/-38.8 ms, post
      exercise: 179.3+/-50.9 ms) (both P<0.05). A significant correlation (R(2)=0.53;
      P<0.05) was identified between the percent reduction of knee extension MVC and
      the percent change in onset time of the knee extensors post exercise. This study
      shows that muscle fatigue induces a reduction and delay in the activation of both
      the quadriceps and hamstring muscles in response to rapid destabilizing
      perturbations potentially reducing the stability around the knee.

PMID- 22366255
TI  - Multimodal event-related potentials in occupational chronic solvent
      encephalopathy.
AB  - The aim of this study was to test a multimodal event-related potential (ERP)
      paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method
      for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13
      healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual
      detection (VIS), and a recognition memory (MEM) task. The auditory and visual
      stimuli were presented in single- and dual-task conditions. The auditory P300
      amplitude in single-task condition was smaller in the patient group than in the
      control group at the parietal (Pz) but not at the frontal midline electrode
      location. The auditory P300 response in the dual task condition AUD+VIS was
      unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM
      condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition,
      the auditory P300 amplitude at Pz was smaller in the patient group than in the
      control group. Reaction time for auditory stimuli in both dual conditions as well
      as for visual stimuli in AUD+VIS condition were in the patient group prolonged.
      The ERP results indicate that CSE patients present with slowed performance speed
      and difficulties in allocation of attention. Based on ERP results, the
      disturbance in brain activity in CSE seems to affect posterior aspects of the
      frontoparietal continuity. The multimodal paradigm seems promising as a tool for
      the clinical diagnostics of CSE.

PMID- 22366256
TI  - [Staphylococcus pseudintermedius and Pasteurella dagmatis associated in a case of
      community-acquired pneumonia].

PMID- 22366257
TI  - GABA(B) receptor-mediated ERK1/2 phosphorylation via a direct interaction with
      Ca(V)1.3 channels.
AB  - Neuronal L-type Ca(2+) channels play pivotal roles in regulating gene expression,
      cell survival, and synaptic plasticity. The Ca(V)1.2 and Ca(V)1.3 channels are 2
      main subtypes of neuronal L-type Ca(2+) channels. However, the specific roles of
      Ca(V)1.2 and Ca(V)1.3 in L-type Ca(2+) channel-mediated neuronal responses and
      their cellular mechanisms are poorly elucidated. On the basis of our previous
      study demonstrating a physical interaction between the Ca(V)1.3 channel and
      GABA(B) receptor (GABA(B)R), we further examined the involvement of Ca(V)1.2 and
      Ca(V)1.3 in the GABA(B)R-mediated activation of ERK(1/2), a kinase involved in
      both CREB activation and synaptic plasticity. After confirming the involvement of
      L-type Ca(2+) channels in baclofen-induced ERK(1/2) phosphorylation, we examined
      a specific role of Ca(V)1.2 and Ca(V)1.3 channels in the baclofen effect. Using
      siRNA-mediated silencing of Ca(V)1.2 or Ca(V)1.3 messenger, we determined the
      relevance of each channel subtype to baclofen-induced ERK(1/2) phosphorylation in
      a mouse hippocampal cell line (HT-22) and primary cultured rat neurons. In the
      detailed characterization of each subtype using HEK293 cells transfected with
      Ca(V)1.2 or Ca(V)1.3, we found that GABA(B)R can increase ERK(1/2)
      phosphorylation and Ca(V)1.3 channel activity through direct interaction with
      Ca(V)1.3 channels. These results suggest a functional interaction between
      Ca(V)1.3 and GABA(B)R and important implications of Ca(V)1.3/GABA(B)R clusters
      for translating synaptic activity into gene expression alterations.

PMID- 22366258
TI  - ISOMAP induced manifold embedding and its application to Alzheimer's disease and
      mild cognitive impairment.
AB  - Neuroimaging data are high dimensional and thus cumbersome to analyze. Manifold
      learning is a technique to find a low dimensional representation for high
      dimensional data. With manifold learning, data analysis becomes more tractable in
      the low dimensional space. We propose a novel shape quantification method based
      on a manifold learning method, ISOMAP, for brain MRI. Existing work applied
      another manifold learning method, multidimensional scaling (MDS), to quantify
      shape information for distinguishing Alzheimer's disease (AD) from normal. We
      enhance the existing methodology by (1) applying it to distinguish mild cognitive
      impairment (MCI) from normal, (2) adopting a more advanced manifold learning
      technique, ISOMAP, and (3) showing the effectiveness of the induced low
      dimensional embedding space to predict key clinical variables such as mini mental
      state exam scores and clinical diagnosis using the standard multiple linear
      regression. Our methodology was tested using 25 normal, 25 AD, and 25 MCI
      patients.

PMID- 22366259
TI  - Postconditioning by mild hypoxic exposures reduces rat brain injury caused by
      severe hypoxia.
AB  - A potent neuroprotective effect of ischemic postconditioning has previously been
      described using cerebral artery occlusion but this is not a practical therapeutic
      option. The present study has been performed to determine whether
      postconditioning by mild episodes of hypobaric hypoxia (hypoxic postconditioning,
      HP) can reduce post-hypoxic brain injury in rats. Male Wistar rats were submitted
      to severe hypobaric hypoxia (180 Torr, 3 h) followed by HP (360 Torr, 2 h, 3
      trials spaced at 24 h) starting either 3h (early HP) or 24 h (delayed HP) after
      severe hypoxia. The structural and functional brain injury was assessed by a
      complex of histological techniques, behavioral methods, and by testing the
      functions of the hypothalamic-pituitary-adrenal axis (HPA). It was found that
      early and delayed HP considerably attenuated post-hypoxic injury, reducing
      pyknosis, hyperchromatosis, and interstitial brain edema, as well as the rates of
      neuronal loss in hippocampus and neocortex. Delayed HP produced prominent
      anxiolytic effect on rat behavior, preventing development of post-hypoxic
      anxiety. Both modes of HP had beneficial effect on the functioning of HPA, but
      only delayed HP normalized completely the baseline HPA activity and its
      reactivity to stress. The results obtained demonstrate that postconditioning by
      using repetitive episodes of mild hypobaric hypoxia may provide a powerful
      neuroprotective procedure that can be easily adopted for clinical practice and
      recommended as a research tool for identification of endogenous mechanisms
      involved in post-ischemic neuroprotection.

PMID- 22366260
TI  - A family-based association study of dopamine receptor D4 and mental retardation
      in Qinba region of China.
AB  - Dopamine receptor D4 (DRD4) is activated by the neurotransmitter dopamine and
      links to many neurological and psychiatric conditions because of its close
      relationship with prefrontal cortex and other important brain regions. To explore
      the possibility that genetic variants of DRD4 gene predispose to children with
      mental retardation (MR), five target SNPs of DRD4 were selected and genotyped in
      the samples of 163 MR pedigrees from the Qinba region of China. Two SNPs
      (rs752306 and rs3758653) showed weak association with MR (the P values were 0.022
      and 0.015 for dominant model, and 0.027 and 0.015 for recessive model,
      respectively). Although they did not bear the multiple testing corrections, the
      haplotype which contained rs3758653 exhibited a significant association with MR
      (global P values were 0.018 for dominant model and 0.028 for recessive model,
      respectively). The in silico analysis also indicated that rs752306 and rs3758653
      would be biologically meaningful SNPs. Therefore, the present study suggested
      that the genetic variants of DRD4 gene may play an important role in human MR.
      Further investigations, such as confirmation with other independent samples and
      functional studies, may elucidate their effect on gene expression and MR
      susceptibility.

PMID- 22366261
TI  - Involvement of transient receptor potential vanilloid 1 in ectopic pain following
      inferior alveolar nerve transection in rats.
AB  - Chronic pain often develops in the orofacial region after inferior alveolar nerve
      (IAN) injury. In animal models IAN injury often causes severe neuropathic pain
      like behavior in the IAN-innervated region as well as the adjacent region that
      includes the whisker pad skin. However, the basis for the spreading of pain to
      adjacent facial areas after IAN injury is still unknown. In this study we
      determined if the transient receptor potential vanilloid 1 (TRPV1) was associated
      with altered nocifensive behavior evoked by stimulation of the whisker pad skin
      following IAN transection. Grooming behavior after capsaicin injection into the
      whisker pad region was significantly increased after IAN transection and the
      increase in the behavior was reversed by systemic administration of a TRPV1
      antagonist. The number of phosphorylated extracellular signal-regulated kinase
      immunoreactive (IR) neurons in trigeminal spinal subnucleus caudalis and upper
      cervical spinal cord following capsaicin injection into the whisker pad region
      was significantly greater in IAN-transected rats than sham-operated rats. The
      number of TRPV1-IR trigeminal ganglion (TG) neurons innervating the whisker pad
      skin was also increased significantly after IAN transection. The present findings
      suggest that an increase in TRPV1 expression in TG neurons innervating the
      whisker pad skin after IAN transection may underlie the spreading of pain to the
      adjacent whisker pad skin.

PMID- 22366262
TI  - HaCaT keratinocytes exhibit a cholesterol and plasma membrane viscosity gradient
      during directed migration.
AB  - Keratinocyte migration plays an important role in cutaneous wound healing by
      supporting the process of reepithelialisation. During directional migration cells
      develop a polarised shape with an asymmetric distribution of a variety of
      signalling molecules in their plasma membrane. Here, we investigated front-to
      back differences of the physical properties of the plasma membrane of migrating
      keratinocyte-like HaCaT cells. Using FRAP and fluorescence lifetime analysis,
      both under TIR illumination, we demonstrate a reduced viscosity of the plasma
      membrane in the lamellipodia of migrating HaCaT cells compared with the cell
      rears. This asymmetry is most likely caused by a reduced cholesterol content of
      the lamellipodia as demonstrated by filipin staining. siRNA-mediated silencing of
      the cholesterol transporter ABCA1, which is known to redistribute cholesterol
      from rafts to non-raft regions, as well as pharmacological inhibition of this
      transporter with glibenclamide, strongly diminished the viscosity gradient of the
      plasma membrane. In addition, HaCaT cell migration was inhibited by glibenclamide
      treatment. These data suggest a preferential role of non-raft cholesterol in the
      establishment of the asymmetric plasma membrane viscosity.

PMID- 22366263
TI  - Isolation of stem-like cells from spontaneous feline mammary carcinomas:
      phenotypic characterization and tumorigenic potential.
AB  - Current carcinogenesis theory states that only a small subset of tumor cells, the
      cancer stem cells or tumor initiating cells (TICs), are responsible for tumor
      formation and progression. Human breast cancer-initiating cells have been
      identified as CD44-expressing cells, which retain tumorigenic activity and
      display stem cell-like properties. Spontaneous feline mammary carcinoma (FMC) is
      an aggressive cancer, which shows biological similarities to the human tumor
      counterpart. We report the isolation and phenotypic characterization of FMC
      derived stem/progenitor cells, showing in vitro self-renewal, long-lasting
      proliferation and in vivo tumorigenicity. Twenty-one FMC samples were collected,
      histologically classified and characterized for the expression of Ki67, EGFR, ER
      alpha and CD44, by immunohistochemistry. By culture in stem cell permissive
      conditions, we isolated, from 13 FMCs, a CD44-positive subpopulation able to
      survive and proliferate in vitro as mammospheres of different sizes and
      morphologies. When injected in NOD/SCID mice, FMC stem-like cells initiate
      tumors, generating cell heterogeneity and recapitulating the original histotype.
      In serum-containing medium, spheroid cells showed differentiation properties as
      shown by morphological changes, the loss of CD44 expression and tumorigenic
      potential. These data show that stem-defined culture of FMC enriches for TICs and
      validate the use of these cells as a suitable model for comparative oncology
      studies of mammary biology and testing therapeutic strategies aimed at
      eradicating TICs.

PMID- 22366265
TI  - Ciprofloxacin prophylaxis for patients undergoing high-dose chemotherapy and
      autologous stem cell transplantation (ASCT) - a single-center experience.
AB  - PURPOSE: The objective of the study was to evaluate the efficacy of ciprofloxacin
      prophylaxis for patients undergoing high-dose chemotherapy followed by autologous
      stem cell transplantation (ASCT). MATERIALS AND METHODS: The data of 104 patients
      transplanted at the Department of Hematology Medical University of Lodz between
      2005 and 2008 were analyzed. The cohort was divided into two groups depending on
      the administered ciprofloxacin prophylaxis. Conditioning regimens did not differ
      significantly among the groups. Multiple myeloma was the main indication for ASCT
      in both groups. RESULTS: Ciprofloxacin prophylaxis resulted in a statistically
      significant reduction of duration of intravenous (IV) antibiotic treatment in the
      group with prophylaxis (p=0.01). The trend has been observed towards lower
      prevalence of infectious episodes in the prophylaxis group. Positive blood
      cultures were similar in both groups with no significant resistance to
      ciprofloxacin. CONCLUSION: These data demonstrate that ciprofloxacin prophylaxis
      is beneficial for patients treated with ASCT following high dose chemotherapy
      regimen, in terms of the intravenous antibiotics usage. This advantage directly
      translates into economic benefit and may also induce less bacterial resistance
      due to less exposure to antibiotics.

PMID- 22366264
TI  - Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in
      familial adenomatous polyposis derived LT97 colon adenoma cells.
AB  - Chemoprevention would be a desirable strategy to avoid duodenectomy in patients
      with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis.
      We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2
      expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic
      acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells
      derived from a patient with FAP, were exposed to low dose celecoxib and UDCA
      alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic
      acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co
      treatment with low dose celecoxib and UDCA resulted in a decreased cell growth
      (14-17%, p<0.01). A more pronounced decrease (23-27%, p<0.01) was observed in
      LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with
      UDCA, was decreased (p<0.001), either in the absence or presence of celecoxib. In
      LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was
      decreased only in the presence of celecoxib (p<0.05). No clear evidence was found
      for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the
      cellular processes leading to the observed changes in cell growth. In conclusion,
      co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on
      colorectal adenoma cells derived from a patient with FAP, and further research on
      this combination as promising chemopreventive strategy is desired.

PMID- 22366266
TI  - A high cholesterol diet ameliorates hippocampus-related cognitive and
      pathological deficits in ovariectomized mice.
AB  - Both sex hormone deficiency and hypercholesterolemia are related to cognitive
      decline or Alzheimer's disease. However, their interactive influence on the
      neurodegenerative progress is not clear. This study was designed to assess the
      effects of ovarian hormone depletion and high cholesterol diet alone or in
      combination on hippocampus-related cognitive and pathological deficits in adult
      female ICR mice. Depletion of ovarian hormones by ovariectomy for 9 weeks
      resulted in significant spatial learning and memory deficits as revealed by the
      water maze testing. Such cognitive alteration was accompanied with increases in
      neuron death and decreases in choline acetyltransferase activity and synaptopysin
      expression in the hippocampus. On the other hand, the high cholesterol diet (3%
      cholesterol plus normal chow) did not exacerbate, but slightly alleviated
      cognitive decline and significantly attenuated hippocampal pathological changes
      in ovariectomized mice. Moreover, ovariectomized mice fed high cholesterol had
      increased serum estrogen levels compared with those fed a normal chow. These
      results indicate that high cholesterol intake increases the sex hormone synthesis
      and in turn partially attenuates hippocampus-related cognitive and pathological
      deficits caused by ovariectomy.

PMID- 22366267
TI  - Some stereotypic behaviors in rhesus macaques (Macaca mulatta) are correlated
      with both perseveration and the ability to cope with acute stressors.
AB  - The most prevalent sub-group of abnormal repetitive behaviors among captive
      animals is that of stereotypies. Previous studies have demonstrated some
      resemblance between stereotypy in captive animals and in humans, including the
      involvement of neurological malfunctions that lead to the expression of
      stereotypies. This malfunction can be evaluated through the use of
      neuropsychological tasks that assess perseveration as implying a failure of the
      basal ganglia (BG) to operate properly. Other studies, in contrast, have
      suggested that stereotypies are the product of neurologically intact individuals
      reacting to the abnormal nature of their surroundings, and are possibly
      characterized by an adaptive feature that enables the subject to cope with such
      adversity. Employing neuropsychological tests and also measuring the levels of
      fecal corticoids in captive rhesus macaques, we tested the hypothesis that
      stereotypies are related both to brain pathology and to a coping mechanism with
      stress, resembling accounts by autistic individuals exhibiting basal ganglia
      malfunction, and who report a sense of relief when performing stereotypies. Self
      directed and fine-motor stereotypies exhibited by the monkeys were positively
      correlated with perseveration, suggesting BG malfunction; while self-directed
      stereotypies were also negatively correlated with an increase in fecal corticoids
      following a stress challenge, suggesting a related coping mechanism. We therefore
      suggest that not all repetitive, unvarying, and apparently functionless behaviors
      should be regarded as one homogeneous group of stereotypic behaviors; and that,
      reflecting reports from autistic individuals, self-directed stereotypies in
      captive rhesus monkeys are related both to brain pathology, and to an adaptive
      mechanism that allows those that express them to better cope with acute
      stressors.

PMID- 22366268
TI  - Circadian modulation of passive avoidance is not eliminated in arrhythmic
      hamsters with suprachiasmatic nucleus lesions.
AB  - The expression of passive avoidance (PA) learning in rats displays a daily or
      circadian rhythm in that optimal performance is displayed when the time of
      testing matches the time of training. Lesions of the suprachiasmatic nucleus
      (SCN) were later shown to abolish this rhythm. Using golden hamsters, we have
      since demonstrated similar rhythms of performance in a conditioned place
      avoidance (CPA) task but unlike the PA results in rats, the rhythmic expression
      of CPA was maintained in arrhythmic hamsters with lesions of the SCN. We
      determined whether PA performance in hamsters is dependent on the SCN (as in the
      rat) or independent (as in the hamster CPA). Performance on the PA task was
      rhythmic in intact control animals with optimal performance occurring when
      training and testing time matched and significantly diminished at both 6h before
      and 6h after training time. SCN-lesions, verified by the loss of behavioral
      circadian rhythms, had no effect on the rhythmic expression. Therefore, time of
      day modulation of PA performance in the hamster does not depend on the SCN
      circadian clock.

PMID- 22366269
TI  - Dengue-3 encephalitis promotes anxiety-like behavior in mice.
AB  - Dengue virus is a human pathogen that may cause meningoencephalitis and other
      neurological syndromes. The current study investigated anxiety-like behavior and
      expression of proinflammatory cytokines and pro-apoptotic caspase-3 in the
      hippocampus of C57BL/6 mice infected with non-adapted Dengue virus 3 genotype I
      (DENV-3) inoculated intracranially with 4*10(3) (plaque-forming unit) PFU.
      Anxiety-like behavior was assessed in control and DENV-3 infected mice using the
      elevated plus maze. The open field test was performed to evaluate locomotor
      activity. Histopathological changes in CA regions of the hippocampus were
      assessed by haematoxylin and eosin staining. Immunoreactive and protein levels of
      cleaved caspase-3 were also analyzed in the hippocampus. The mRNA expression of
      IL-6 and TNF-alpha in the hippocampus were estimated by quantitative real time
      (polymerase chain reaction) PCR. All procedures were conducted on day 5 post
      infection. We found that DENV-3 infected mice presented higher levels of anxiety
      in comparison with controls (p<=0.05). No difference in motor activity was found
      between groups (p=0.77). The infection was followed by a significant increase of
      TNF-alpha and IL-6 mRNA expression in the hippocampus (p<=0.05). Histological
      analysis demonstrated meningoencephalitis with formation of perivascular cuffs,
      infiltration of immune cells and loss of neurons at CA regions of hippocampus.
      Numerous caspase-3 positive neurons were visualized at CA areas in DENV-3
      infected mice. Marked increase of cleaved caspase-3 levels were observed after
      infection. This study described anxiety-like behavior, hippocampal inflammation
      and neuronal apoptosis associated with DENV-3 infection in the central nervous
      system.

PMID- 22366270
TI  - Repeated cycles of restricted food intake and binge feeding disrupt sensory
      specific satiety in the rat.
AB  - The relationship between food restriction and subsequent dysregulation of food
      intake is complex, variable and long-lasting. The present study investigated in
      rats whether repeated cycles of food restriction and binge feeding opportunities
      may alter regulation of food intake by employing a test for sensory-specific
      satiety. Rats that experienced repeated food restriction-binge cycles maintained
      heavier body weights compared to rats that remained on continuous food
      restriction. In contrast to the control subjects, rats that alternated between
      food restriction and binge feeding failed to display sensory-specific satiety.
      During the first meal, there was a gradual decrease in the amount of food intake
      over a 40 min period. When presented with a second meal of the same food, these
      rats responded to the familiar food in a manner similar as to a novel food (i.e.,
      comparable quantities of both types of food were consumed). Food restriction
      binge feeding cycles may be considered as a form of stress, which in turn is
      associated with cross-sensitization to numerous behavioral responses. Therefore,
      we propose that stress-induced disruption of sensory-specific satiety reflects a
      sensitized response to food, in which the interaction between sensory and satiety
      factors are no longer the key regulators of food choice and meal cessation.
      Furthermore, a role for sensory-specific satiety in terminating food intake
      appeared to decline with the progression of the cycles, thereby contributing to a
      steady increase in body weight of rats that experienced restriction with bouts of
      binge feeding opportunities.

PMID- 22366271
TI  - Venlafaxine facilitates between-session extinction and prevents reinstatement of
      auditory-cue conditioned fear.
AB  - Anxiety disorders, characterized by anxiety and fearfulness, are found to be able
      to cause abnormal emotional responses' associated with memories of negative
      events, which implicate pressure on society with an increasingly large burden.
      Better treatment has been of concern to the community. Venlafaxine (VEN), a
      nonclassical antidepressant agent, is applied in the treatment of social phobia,
      major depression (MD) and general anxiety disorder (GAD) and, to a certain
      extent, posttraumatic stress disorder (PTSD), which improves working memory and
      spatial memory as well as ameliorates emotion by affecting specified brain
      regions. In this study, we committed to seek a new way for using VEN on treatment
      of anxiety disorders. To investigate the effect of VEN on extinction of auditory
      cue conditioned fear, conditioned rats received a treatment with VEN before
      extinction training and tests for freezing level of within-session and between
      session extinction. To investigate the effect of VEN on reinstatement, all
      conditioned rats received a treatment with VEN over a period for 21 days. After a
      rest for 7 days, two tests for freezing level were conducted. We found that: (1)
      VEN (40mg/kg) treatment at 30min prior to extinction training significantly
      facilitated the between-session extinction, but not the within-session
      extinction; (2) chronic administration with VEN (40mg/kg) prevented the return of
      extinguished auditory-cue fear. These data elucidate the critical role of VEN in
      auditory-cue fear memory, suggesting that VEN may be an ideal choice for the
      exposure-based drug treatment and maintenance treatment in patients with GAD, SAD
      and PTSD.

PMID- 22366272
TI  - Dorsal hippocampal lesions disrupt Pavlovian delay conditioning and conditioned
      response timing.
AB  - The involvement of the rat dorsal hippocampus (dhpc) in Pavlovian conditioning
      and timing of conditioned responding was examined in an appetitive preparation in
      which presentation of a relatively long, 40-s auditory conditioned stimulus (CS)
      was followed immediately by food delivery. Dorsal hippocampal lesions impaired
      Pavlovian conditioning in this task. They also produced a deficit in interval
      timing, replicating previous findings with short CSs. The conditioning and timing
      deficits observed are consistent with the findings from single-unit recording
      studies in other species, and suggest that the involvement of the dhpc in
      Pavlovian processes could be more general than is assumed by many of the current
      theories of hippocampal function.

PMID- 22366273
TI  - Methylglyoxal-induced modifications of significant honeybee proteinous components
      in manuka honey: Possible therapeutic implications.
AB  - Methylglyoxal (MGO) is a major antibacterial component of manuka honey. Another
      antibacterial component found in Revamil honey, peptide defensin1, was not
      identified in manuka honey. The primary aim of the study was to evaluate the
      content of defensin1 in honeys of different botanical origins and to investigate
      a presumed effect of reactive MGO on defensin1 and a dominant protein of honey
      MRJP1 in manuka honey. Immunoblotting of honey samples showed that defensin1 was
      a regular but quantitatively variable component of honeys. One of the reasons of
      varying contents of defensin1 in different honeys seems to be constitutive but
      varying defensin1 expression in individual honeybees in bee populations that we
      documented on samples of nurse and forager bees by RT-PCR. Comparative analyses
      of honeys revealed a size modification of defensin1, MRJP1 and probably also
      alpha-glucosidase in manuka honey. We further showed that (i) the treatment of
      purified defensin1 in solution containing high amount of MGO caused a time
      dependent loss of its antibacterial activity and (ii) increasing MGO
      concentrations in a non-manuka honey were connected with a gradual increase in
      the molecular weight of MRJP1. Obtained results demonstrate that MGO abrogates
      the antibacterial activity of defensin1 and modifies MRJP1 in manuka honey. We
      assume that MGO could also have negative effects on the structure and function of
      other proteins/peptides in manuka honey, including glucose oxidase, generating
      hydrogen peroxide.

PMID- 22366274
TI  - Dyskinetic patients show rebound worsening of affect after an acute L-dopa
      challenge.
AB  - BACKGROUND: Motor response complications that arise with repeated L-dopa
      administration for the treatment of Parkinson's disease are well understood but
      the relationship between motor response complications and affect are not. We
      proposed that patients with dyskinesias would report rebound worsening in affect
      during wearing-off of L-dopa effect. METHODS: Fifty Parkinson's disease patients
      with were assessed with the Purdue Pegboard test and rated Positive Affect and
      Negative Affect after overnight withdrawal of dopaminergic medications and half
      hourly for 6 h after a standard L-dopa challenge. Patients were carefully
      classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n
      = 23) groups. RESULTS: Positive Affect was improved by L-dopa in dyskinetics and
      to a lesser degree in fluctuators but not in stable responders. At T = 4-6 h,
      Positive Affect rebounded below baseline in dyskinetics only. On regression
      analysis, rebound worsening positively correlated with ratings of dyskinesia
      severity. Negative Affect improved with L-dopa in all groups and tended to remain
      below baseline for 6 h after L-dopa challenge. Peak effects of L-dopa on Positive
      Affect and Negative Affect occurred significantly earlier than effects on Purdue
      Pegboard test and were positively correlated with L-dopa equivalent daily dose.
      CONCLUSION: There is a clinical dissociation between L-dopa effects on motor
      function, Positive Affect and Negative Affect. Rebound worsening in Positive
      Affect occurred only in dyskinetic patients and the onset of rebound worsening
      occurred before the end of the motor benefit phase. These observations could
      explain why some Parkinson patients report wearing-off symptoms despite the
      external impression of good motor control.

PMID- 22366275
TI  - Heart rate variability in patients with idiopathic Parkinson's disease with and
      without obstructive sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with repeated
      apnea-induced sympathetic surges leading to specific alterations of the power
      spectrum of heart rate variability (HRV). Sympathetic dysfunction evolves early
      in idiopathic Parkinson's disease (PD), but the consequences on cardiac autonomic
      response to OSAS have not been studied so far in PD patients. METHODS: Sixty-two
      patients with PD (35 without OSAS (PD-wo), 27 with OSAS (PD-OSAS)) and 62 age
      matched control subjects (25 without OSAS (Co-wo), 37 with OSAS (Co-OSAS)) were
      included. HRV variables - including mean R-R interval, standard deviation of all
      normal-to-normal R-R intervals (SDNN), both low frequency (LF) and high frequency
      (HF) power bands, and the LF/HF ratio - were computed automatically from full
      night polysomnography and calculated separately for each sleep stage. RESULTS:
      HRV variables were similar in PD-wo and PD-OSAS. In contrast, Co-OSAS showed
      significantly higher LF power in NREM1 and NREM2 sleep and higher LF/HF ratio in
      NREM1, NREM2 and slow wave sleep than Co-wo. Similarly, correlations between HRV
      variables and parameters of OSAS severity were found only in controls but not in
      PD patients. CONCLUSION: Our results suggest that the sympathetic response to
      OSAS is blunted in PD, giving further clinical evidence of the sympathetic
      denervation commonly observed in this neurodegenerative disorder.

PMID- 22366276
TI  - The dual lives of bidirectional promoters.
AB  - The sequencing of the human genome led to many insights into gene organization
      and structure. One interesting observation was the high frequency of
      bidirectional promoters characterized by two protein encoding genes whose
      promoters are arranged in a divergent or "head-to-head" configuration with less
      than 2000 base pairs of intervening sequence. Computational estimates published
      by various groups indicate that nearly 10% of the coding gene promoters are
      arranged in such a manner and the extent of this bias is a unique feature of
      mammalian genomes. Moreover, as a class, head-to-head promoters appear to be
      enriched in specific categories of gene function. Here we review the structure,
      composition, genomic properties and functional classifications of genes
      controlled by bidirectional promoters and explore the biological implication of
      these features. This article is part of a Special Issue entitled: Chromatin in
      time and space.

PMID- 22366277
TI  - Beam-induced motion of vitrified specimen on holey carbon film.
AB  - The contrast observed in images of frozen-hydrated biological specimens prepared
      for electron cryo-microscopy falls significantly short of theoretical
      predictions. In addition to limits imposed by the current instrumentation, it is
      widely acknowledged that motion of the specimen during its exposure to the
      electron beam leads to significant blurring in the recorded images. We have
      studied the amount and direction of motion of virus particles suspended in thin
      vitrified ice layers across holes in perforated carbon films using exposure
      series. Our data show that the particle motion is correlated within patches of
      0.3-0.5 MUm, indicating that the whole ice layer is moving in a drum-like motion,
      with accompanying particle rotations of up to a few degrees. Support films with
      smaller holes, as well as lower electron dose rates tend to reduce beam-induced
      specimen motion, consistent with a mechanical effect. Finally, analysis of movies
      showing changes in the specimen during beam exposure show that the specimen moves
      significantly more at the start of an exposure than towards its end. We show how
      alignment and averaging of movie frames can be used to restore high-resolution
      detail in images affected by beam-induced motion.

PMID- 22366278
TI  - Crystal structures of the reverse transcriptase-associated ribonuclease H domain
      of xenotropic murine leukemia-virus related virus.
AB  - The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT)
      plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA
      hybrids. In addition, RNase H activity is required to precisely remove the RNA
      primers from nascent (-) and (+) strand DNA. We report here three crystal
      structures of the RNase H domain of xenotropic murine leukemia virus-related
      virus (XMRV) RT, namely (i) the previously identified construct from which helix
      C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with
      an active site alpha-hydroxytropolone inhibitor. Enzymatic assays showed that the
      intact RNase H domain retained catalytic activity, whereas the variant lacking
      helix C was only marginally active, corroborating the importance of this helix
      for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the
      essential role of helix C in binding a DNA/RNA hybrid and its likely mode of
      recognition. The crystal structure of the RNase H domain complexed with beta
      thujaplicinol clearly showed that coordination by two divalent cations mediates
      recognition of the inhibitor.

PMID- 22366279
TI  - The crystal structure of the dimeric colicin M immunity protein displays a 3D
      domain swap.
AB  - Bacteriocins are proteins secreted by many bacterial cells to kill related
      bacteria of the same niche. To avoid their own suicide through reuptake of
      secreted bacteriocins, these bacteria protect themselves by co-expression of
      immunity proteins in the compartment of colicin destination. In Escherichia coli
      the colicin M (Cma) is inactivated by the interaction with the Cma immunity
      protein (Cmi). We have crystallized and solved the structure of Cmi at a
      resolution of 1.95A by the recently developed ab initio phasing program
      ARCIMBOLDO. The monomeric structure of the mature 10kDa protein comprises a long
      N-terminal alpha-helix and a four-stranded C-terminal beta-sheet. Dimerization of
      this fold is mediated by an extended interface of hydrogen bond interactions
      between the alpha-helix and the four-stranded beta-sheet of the symmetry related
      molecule. Two intermolecular disulfide bridges covalently connect this dimer to
      further lock this complex. The Cmi protein resembles an example of a 3D domain
      swapping being stalled through physical linkage. The dimer is a highly charged
      complex with a significant surplus of negative charges presumably responsible for
      interactions with Cma. Dimerization of Cmi was also demonstrated to occur in
      vivo. Although the Cmi-Cma complex is unique among bacteria, the general fold of
      Cmi is representative for a class of YebF-like proteins which are known to be
      secreted into the external medium by some Gram-negative bacteria.

PMID- 22366280
TI  - Evaluation of enantioselective binding of propanocaine to human serum albumin by
      ultrafiltration and electrokinetic chromatography under intermediate precision
      conditions.
AB  - Stereoselectivity in protein binding can have a significant effect on the
      pharmacokinetic and pharmacodynamic properties of chiral drugs. In this paper,
      the enantioselective binding of propanocaine (PRO) enantiomers to human serum
      albumin (HSA), the most relevant plasmatic protein in view of stereoselectivity,
      has been evaluated by incubation and ultrafiltration of racemic PRO-HSA mixtures
      and chiral analysis of the bound and unbound fractions by electrokinetic
      chromatography using HSA as chiral selector. Experimental conditions for the
      separation of PRO enantiomers using HSA as chiral selector and electrokinetic
      chromatography have been optimised. Affinity constants and protein binding in
      percentage (PB) were obtained for both enantiomers of PRO, as well as the
      enantioselectivity (ES) to HSA. Data were obtained in two independent working
      sessions (days). The influence of the session and fraction processed factors were
      examined. A univariate direct-estimation approach was used facilitating outliers'
      identification and statistical comparison. Non-linear fitting of data was used to
      verify the stoichiometry and affinity estimations obtained by the direct
      approach. Robust statistics were applied to obtain reliable estimations of
      uncertainty, accounting for the factors (day and processed fraction), thus
      representing intermediate precision conditions. Mimicking in vivo experimental
      conditions, information unapproachable by in vivo experiments was obtained for
      PRO enantiomers interacting with HSA. For the first (E1) and the second (E2)
      eluted PRO enantiomers the results were: 1:1 stoichiometry, medium affinity
      constants, logK(E1)=3.20+/-0.16 and log K(E2)=3.40+/-0.14, medium protein binding
      percentage, PB=48.7 and 60.1% for E1 and E2, respectively, and moderate but
      significant enantioselectivity, ES=K(E2)/K(E1)=1.5+/-0.3.

PMID- 22366281
TI  - Quantification of carbamazepine and its active metabolite by direct injection of
      human milk serum using liquid chromatography tandem ion trap mass spectrometry.
AB  - This work reports the use of a liquid chromatography ion trap tandem mass
      spectrometry (LC-IT-MS/MS) system for quantification in human milk samples of
      both carbamazepine (CBZ) and its active metabolite, carbamazepine 10,11-epoxide
      (CBZE). An octadecyl restricted-access media bovine serum albumin column (RAM-BSA
      C(18)) was used in single-column mode. Selectivity, extraction efficiency,
      accuracy and precision were achieved employing 100 MUL of the sample, without
      preparation, with detection limits of 20.0 ng/mL for CBZ and 40.0 ng/mL for CBZE.
      The matrix effect was investigated for the compounds by post-column infusion
      (qualitative) and by on-line extraction (quantitative). It was observed
      suppression effect for CBZ and CBZE by post-column infusion, ion suppression of
      0.80 for CBZ, and enhancement of 1.28 for CBZE by on-line extraction. The
      developed method was validated and applied to analyze breast milk samples from
      one nursing mother. CBZ and CBZE were quantified in the concentrations of 2.26
      MUg/mL and 1.54 MUg/mL, respectively. To our knowledge, this is the first report
      on the simultaneous determination of CBZ and its active metabolite by direct
      injection of human milk serum.

PMID- 22366282
TI  - Quantification of blending of olive oils and edible vegetable oils by
      triacylglycerol fingerprint gas chromatography and chemometric tools.
AB  - A reliable procedure for the identification and quantification of the
      adulteration of olive oils in terms of blending with other vegetable oils
      (sunflower, corn, seeds, sesame and soya) has been developed. From the analytical
      viewpoint, the whole procedure relies only on the results of the determination of
      the triacylglycerol profile of the oils by high temperature gas chromatography
      mass spectrometry. The chromatographic profiles were pre-treated (baseline
      correction, peak alignment using iCoshift algorithm and mean centering) before
      building the models. At first, a class-modeling approach, Soft Independent
      Modeling of Class Analogy (SIMCA) was used to identify the vegetable oil used
      blending. Successively, a separate calibration model for each kind of blending
      was built using Partial Least Square (PLS). The correlation coefficients of
      actual versus predicted concentrations resulting from multivariate calibration
      models were between 0.95 and 0.99. In addition, Genetic algorithms (GA-PLS), were
      used, as variable selection method, to improve the models which yielded R(2)
      values higher than 0.90 for calibration set. This model had a better predictive
      ability than the PLS without feature selection. The results obtained showed the
      potential of this method and allowed quantification of blends of olive oil in the
      vegetable oils tested containing at least 10% of olive oil.

PMID- 22366283
TI  - Quantitation of bentysrepinine (Y101) in rat plasma by liquid chromatography
      tandem mass spectrometry: application to pharmacokinetic study.
AB  - A simple, accurate and sensitive liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method was developed and validated for quantitation of bentysrepinine
      (Y101) in rat plasma. After the addition of diphenhydramine (internal standard,
      IS), plasma samples were pretreated by protein precipitation. Chromatographic
      separation was carried out on an Atlantis((r)) analytical column (4.6 mm * 100
      mm, 5 MUm, Waters) with methanol: 20 mM ammonium formate consisting of 1.0%
      formic acid (65:35, v/v) as the mobile phase at an isocratic flow rate of 0.4
      mL/min for 7.5 min. The multiple reaction monitoring (MRM) transitions were
      performed at m/z 490.2->339.5 for Y101 and m/z 256.0->167.0 for IS on a SCIEX API
      4000 mass spectrometer in the positive ion mode with electrospray ionization
      (ESI) source. Good linearity was achieved over the concentration range of 1-2500
      ng/mL. The intra- and inter-day precisions were less than 8.3%, and the accuracy
      ranged from -4.0% to 2.8%. Y101 was stable during the analysis and the storage
      period. The pharmacokinetic profiles of Y101 at three dose levels were
      successfully studied for the first time in rats by this method. After single
      intra-gastric administration of Y101 at the doses of 25, 50 and 100 mg/kg, C(max)
      and AUC(0-t) were proportional to the doses given.

PMID- 22366284
TI  - Prednisolone exerts exquisite inhibitory properties on platelet functions.
AB  - We have previously reported presence of the glucocorticoid (GC) receptor (GR)
      alpha on blood platelets, and its ability to modulate platelet aggregation when
      activated by the synthetic GC prednisolone (Pred). In the present study we
      investigated the effects of Pred on broader aspects of platelet functions to
      unveil novel non-genomic actions on this cell type. Using whole blood assay we
      demonstrated that Pred was the only GC able to inhibit platelet aggregation and
      platelet-monocyte interactions. This latter effect was due to regulation of
      platelets, not monocytes. We next examined the effects of Pred on physiological
      actions of platelets, observing inhibition of platelet adhesion and spreading on
      collagen under static conditions. Moreover Pred inhibited thrombus formation
      under flow, suggesting potential important effects in haemostasis and thrombosis.
      Pred was unable to regulate platelet reactivity under conditions where the
      effects of platelet-derived ADP and TxA2 were blocked, suggesting that the GC
      targeted the activation-dependent component of the adhesion and aggregation
      response. The effects of Pred were not mediated through cyclic nucleotide
      signaling, but rather seemed to evolve around selective regulation of P2Y12 ADP
      receptor signaling, intimating a novel mode of action. This study details the
      actions of Pred on platelets unveiling novel properties which could be relevant
      for this GC in controlling unwanted vascular and thrombotic diseases.

PMID- 22366285
TI  - Appetite, energy intake and resting metabolic responses to 60 min treadmill
      running performed in a fasted versus a postprandial state.
AB  - This study investigated the effect of fasted and postprandial exercise on
      appetite, energy intake and resting metabolic responses. Twelve healthy males
      (mean+/-SD: age 23+/-3 years, body mass index 22.9+/-2.1 kg m(-2), maximum oxygen
      uptake 57.5+/-9.7 mL kg(-1) min(-1)) performed three 10 h experimental trials
      (control, fasted exercise and postprandial exercise) in a Latin Square design.
      Trials commenced at 8 am after an overnight fast. Sixty min of treadmill running
      at ~70% of maximum oxygen uptake was performed at 0-1 h in the fasted exercise
      trial and 4-5 h in the postprandial exercise trial. A standardised breakfast was
      provided at 1.5 h and ad libitum buffet meals at 5.5 and 9.5 h. Appetite ratings
      and resting expired air samples were collected throughout each trial.
      Postprandial exercise suppressed appetite to a greater extent than fasted
      exercise. Ad libitum energy intake was not different between trials, resulting in
      a negative energy balance in exercise trials relative to control after accounting
      for differences in energy expenditure (control: 9774+/-2694 kJ; fasted exercise:
      6481+/-2318 kJ; postprandial exercise: 6017+/-3050 kJ). These findings suggest
      that 60 min treadmill running induces a negative daily energy balance relative to
      a sedentary day but is no more effective when performed before or after
      breakfast.

PMID- 22366286
TI  - Pulmonary vein anatomy assessment prior to atrial fibrillation ablation using
      balloon-based technologies: can it really be abandoned?

PMID- 22366287
TI  - Matrikines and the lungs.
AB  - The extracellular matrix is a complex network of fibrous and nonfibrous molecules
      that not only provide structure to the lung but also interact with and regulate
      the behaviour of the cells which it surrounds. Recently it has been recognised
      that components of the extracellular matrix proteins are released, often through
      the action of endogenous proteases, and these fragments are termed matrikines.
      Matrikines have biological activities, independent of their role within the
      extracellular matrix structure, which may play important roles in the lung in
      health and disease pathology. Integrins are the primary cell surface receptors,
      characterised to date, which are used by the matrikines to exert their effects on
      cells. However, evidence is emerging for the need for co-factors and other
      receptors for the matrikines to exert their effects on cells. The potential for
      matrikines, and peptides derived from these extracellular matrix protein
      fragments, as therapeutic agents has recently been recognised. The natural role
      of these matrikines (including inhibitors of angiogenesis and possibly
      inflammation) make them ideal targets to mimic as therapies. A number of these
      peptides have been taken forward into clinical trials. The focus of this review
      will be to summarise our current understanding of the role, and potential for
      highly relevant actions, of matrikines in lung health and disease.

PMID- 22366288
TI  - Histone deacetylase (HDAC) inhibitors and regulation of TRAIL-induced apoptosis.
AB  - Evasion of apoptosis represents a key mechanism leading to treatment resistance
      of human cancers. Abnormal regulation of chromatin remodeling has been implied in
      tumorigenesis as well as treatment resistance. Acetylation of histones represents
      one of the key posttranslational modifications that contribute to the regulation
      of chromatin remodeling. Histone acetylation is governed by the balance between
      enzymes that put acetyl groups on histone tails or, alternatively, remove them.
      Since a disturbed regulation of histone acetylation plays an important role in
      cancer formation and progression, a variety of histone deacetylase (HDAC)
      inhibitors have been developed in recent years to target aberrant HDAC activity.
      HDAC inhibitors also represent a promising strategy to lower the threshold of
      cancer cells for apoptosis induction. For example, synergistic induction of
      apoptosis has been documented for the concomitant use of HDAC inhibitors together
      with the death receptor ligand TRAIL in a panel of human cancers. Understanding
      the molecular mechanism that mediates this synergistic drug interaction will be
      critical to further optimize this approach in order to successfully translate it
      into a clinical setting.

PMID- 22366289
TI  - Autophagy is a survival force via suppression of necrotic cell death.
AB  - Macroautophagy or autophagy is a self-digesting mechanism that the cellular
      contents are engulfed by autophagosomes and delivered to lysosomes for
      degradation. Although it has been well established that autophagy is an important
      protective mechanism for cells under stress such as starvation via provision of
      nutrients and removal of protein aggregates and damaged mitochondria, there is a
      very complex relation between autophagy and cell death. At present, the molecular
      cross-talk between autophagy and apoptosis has been well discussed, while the
      relationship between autophagy and programmed necrotic cell death is less
      understood. In this review we focus on the role of autophagy in necrotic cell
      death by detailed discussion on two important forms of necrotic cell death: (i)
      necroptosis and (ii) poly-(ADP-ribose) polymerase (PARP)-mediated cell death. It
      is believed that one important aspect of the pro-survival function of autophagy
      is achieved via its ability to block various forms of necrotic cell death.

PMID- 22366290
TI  - Evaluation of propofol containing 2% benzyl alcohol preservative in cats.
AB  - Propofol emulsion containing benzyl alcohol preservative (BA) was evaluated in
      cats. Eight (PB) received 1% propofol containing 2% benzyl alcohol and eight (PC)
      preservative-free propofol. In phase 1, cats were anaesthetised (8 mg/kg) three
      times at 48 h intervals. In phase 2, cats underwent three anaesthetic procedures
      at 48 h intervals where anaesthesia was maintained until 24 mg/kg had been
      administered. Clinical examination and haematological and biochemical analyses
      were performed regularly. Cardiorespiratory function was monitored throughout
      anaesthesia. Neurological examination was performed daily for 7 days after phase
      2. All cats were euthanased 7 days after phase 2 and examined post mortem to
      determine any organ toxicity and to comply with regulatory requirements.
      Anaesthesia was as expected for propofol in cats and no clinically relevant
      differences between PB and PC were detected. The addition of BA has no additional
      effect when propofol is used at normal-to-high clinical doses in healthy cats.

PMID- 22366291
TI  - Effects of an agonist interleukin-2/Fc fusion protein, a mutant antagonist
      interleukin-15/Fc fusion protein, and sirolimus on cardiac allograft survival in
      non-human primates.
AB  - BACKGROUND: To tilt the immunologic balance toward tolerance and away from
      rejection, non-human primate recipients of cardiac allografts were treated with
      interleukin (IL)-2/Fc, mutant (m) antagonist type mIL-15/Fc, and sirolimus.
      METHODS: Heterotopic heart transplants were performed on 8 fully mismatched
      cynomolgus macaques. An untreated control recipient rejected its graft by post
      operative Day 6. The remaining 7 animals received oral or intramuscular
      immunosuppression with sirolimus. A recipient treated with sirolimus alone
      rejected at the end of 28 days of immunosuppression. The remaining 6 monkeys also
      received IL-2/Fc and mIL-15/Fc intramuscularly until 28 days after transplant.
      One animal received a second 28-day course of fusion protein starting at Day 50.
      In these 6 animals, sirolimus was continued for 28 days (n = 4) or until protein
      levels were low (n = 2). RESULTS: In the 4 monkeys treated with a 28-day course
      of sirolimus and fusion proteins, mean graft survival was 51.5 days (range, 28-76
      days). The animal receiving a second course of fusion protein rejected its graft
      on Day 177, despite detectable levels of the fusion proteins and sirolimus. The
      central memory, effector memory, and naive CD4(+) and CD8(+) T-cell populations
      in the peripheral blood did not change significantly during fusion protein
      administration. A 2.5-fold expansion in CD4(+)CD25(+) lymphocytes occurred in
      recipients treated with fusion proteins and sirolimus that was not observed in
      the recipient treated with sirolimus alone. CONCLUSIONS: Although IL-2/Fc, mIL
      15/Fc, and sirolimus administered in this manner permitted modest prolongation of
      graft survival and expansion of CD4(+)CD25(+) T cells, tolerance was not
      achieved.

PMID- 22366292
TI  - Reproducibility of mass spectrometry based protein profiles for diagnosis of
      ovarian cancer across clinical studies: A systematic review.
AB  - The focus of this systematic review is to give an overview of the current status
      of clinical protein profiling studies using MALDI and SELDI MS platforms in the
      search for ovarian cancer biomarkers. A total of 34 profiling studies were
      qualified for inclusion in the review. Comparative analysis of published
      discriminatory peaks to peaks found in an original MALDI MS protein profiling
      study was made to address the key question of reproducibility across studies. An
      overlap was found despite substantial heterogeneity between studies relating to
      study design, biological material, pre-analytical treatment, and data analysis.
      About 47% of the peaks reported to be associated to ovarian cancer were also
      represented in our experimental study, and 34% of these redetected peaks also
      showed a significant difference between cases and controls in our study. Thus,
      despite known problems related to reproducibility an overlap in peaks between
      clinical studies was demonstrated, which indicate convergence toward a set of
      common discriminating, reproducible peaks for ovarian cancer. The potential of
      the discriminating protein peaks for clinical use as ovarian cancer biomarkers
      will be discussed and evaluated. This article is part of a Special Issue
      entitled: Proteomics: The clinical link.

PMID- 22366293
TI  - Implementation of the Department of Veterans Affairs' first point-of-care
      clinical trial.
AB  - OBJECTIVES: The Massachusetts Veterans Epidemiology Research and Information
      Center in collaboration with the Stanford Center for Innovative Study Design set
      out to test the feasibility of a new method of evidence generation. The first
      pilot of a point-of-care clinical trial (POCCT), adding randomization and other
      study processes to an electronic medical record (EMR) system, was launched to
      compare the effectiveness of two insulin regimens. MATERIALS AND METHODS:
      Existing functionalities of the Veterans Affairs (VA) computerized patient record
      system (CPRS)/veterans health information systems and technology architecture
      (VISTA) were modified to support the activities of a randomized controlled trial
      including enrolment, randomization, and longitudinal data collection. RESULTS:
      The VA's CPRS/VISTA was successfully adapted to support the processes of a
      clinical trial and longitudinal study data are being collected from the medical
      record automatically. As of 30 June 2011, 55 of the 67 eligible patients
      approached received a randomized intervention. DISCUSSION: The design of
      CPRS/VISTA made integration of study workflows and data collection possible.
      Institutions and investigators considering similar designs must carefully map
      clinical workflows and clinical trial workflows to EMR capabilities. POCCT study
      teams are necessarily interdisciplinary and interdepartmental. As a result,
      executive sponsorship is critical. CONCLUSION: POCCT represent a promising new
      method for conducting clinical science. Much work is needed to understand better
      the optimal uses and designs for this new approach. Next steps include focus
      groups to measure patient and clinician perceptions, multisite deployment of the
      current pilot, and implementation of additional studies.

PMID- 22366294
TI  - Evaluating the state of the art in coreference resolution for electronic medical
      records.
AB  - BACKGROUND: The fifth i2b2/VA Workshop on Natural Language Processing Challenges
      for Clinical Records conducted a systematic review on resolution of noun phrase
      coreference in medical records. Informatics for Integrating Biology and the
      Bedside (i2b2) and the Veterans Affair (VA) Consortium for Healthcare Informatics
      Research (CHIR) partnered to organize the coreference challenge. They provided
      the research community with two corpora of medical records for the development
      and evaluation of the coreference resolution systems. These corpora contained
      various record types (ie, discharge summaries, pathology reports) from multiple
      institutions. METHODS: The coreference challenge provided the community with two
      annotated ground truth corpora and evaluated systems on coreference resolution in
      two ways: first, it evaluated systems for their ability to identify mentions of
      concepts and to link together those mentions. Second, it evaluated the ability of
      the systems to link together ground truth mentions that refer to the same entity.
      Twenty teams representing 29 organizations and nine countries participated in the
      coreference challenge. RESULTS: The teams' system submissions showed that machine
      learning and rule-based approaches worked best when augmented with external
      knowledge sources and coreference clues extracted from document structure. The
      systems performed better in coreference resolution when provided with ground
      truth mentions. Overall, the systems struggled in solving coreference resolution
      for cases that required domain knowledge.

PMID- 22366295
TI  - Evaluation of an Android-based mHealth system for population surveillance in
      developing countries.
AB  - OBJECTIVE: In parts of the developing world traditionally modeled healthcare
      systems do not adequately meet the needs of the populace. This can be due to
      imbalances in both supply and demand--there may be a lack of sufficient
      healthcare and the population most at need may be unable or unwilling to take
      advantage of it. Home-based care has emerged as a possible mechanism to bring
      healthcare to the populace in a cost-effective, useful manner. This study
      describes the development, implementation, and evaluation of a mobile device
      based system to support such services. MATERIALS AND METHODS: Mobile phones were
      utilized and a structured survey was implemented to be administered by community
      health workers using Open Data Kit. This system was used to support screening
      efforts for a population of two million persons in western Kenya. RESULTS: Users
      of the system felt it was easy to use and facilitated their work. The system was
      also more cost effective than pen and paper alternatives. DISCUSSION: This
      implementation is one of the largest applications of a system utilizing handheld
      devices for performing clinical care during home visits in a resource-constrained
      environment. Because the data were immediately available electronically, initial
      reports could be performed and important trends in data could thus be detected.
      This allowed adjustments to the programme to be made sooner than might have
      otherwise been possible. CONCLUSION: A viable, cost-effective solution at scale
      has been developed and implemented for collecting electronic data during
      household visits in a resource-constrained setting.

PMID- 22366296
TI  - Superoxide signaling and cell death in retinal ganglion cell axotomy: effects of
      metallocorroles.
AB  - Injury to retinal ganglion cell (RGC) axons within the optic nerve causes
      apoptosis of the soma. We previously demonstrated that in vivo axotomy causes
      elevation of superoxide anion within the RGC soma, and that this occurs 1-2 days
      before annexin-V positivity, a marker of apoptosis. Pegylated superoxide
      dismutase delivery to the RGC prevents the superoxide elevation and rescues the
      soma. Together, these results imply that superoxide is an upstream signal for
      apoptosis after axonal injury in RGCs. We then studied metallocorroles, potent
      superoxide dismutase mimetics, which we had shown to be neuroprotective in vitro
      and superoxide scavengers in vivo for RGCs. RGCs were retrograde labeled with the
      fluorescent dye 4Di-10Asp, and then axotomized by intraorbital optic nerve
      transection. Iron(III) 2,17-bis-sulfonato-5,10,15-tris(pentafluorophenyl)corrole
      (Fe(tpfc)(SO(3)H)(2)) (Fe-corrole) was injected intravitreally. Longitudinal
      imaging of RGCs was performed and the number of surviving RGCs enumerated. There
      was significantly greater survival of labeled RGCs with Fe-corrole, but the
      degree of neuroprotection was relatively less than that predicted by their
      ability to scavenge superoxide-This implies an unexpected complexity in signaling
      of apoptosis by reactive oxygen species.

PMID- 22366298
TI  - Dual therapy in IPAH and SSc-PAH. A qualitative systematic review.
AB  - BACKGROUND: Use of endothelin receptor antagonists (ERA), phosphodiesterase type
      5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved
      outcomes in idiopathic pulmonary arterial hypertension (IPAH) and systemic
      sclerosis-associated PAH (SSc-PAH) patients. However, patients often deteriorate
      on monotherapy. The objective of this study is to evaluate the effect of dual
      therapy on outcomes in IPAH and SSc-PAH. METHODS: A systematic review of MEDLINE
      (1950-2011), EMBASE (1980-2011) and CINAHL (inception-2011) was conducted to
      identify studies that evaluated the effect of any dual combination of ERA, PDE-5
      inhibitors or prostaglandin analogues on 6-min walk distance (6MWD), functional
      class (FC), haemodynamics, quality-of-life (QoL) or time-to-clinical-worsening in
      IPAH or SSc-PAH. A standardized form was used to abstract design, sample size,
      aetiology, outcome and treatment effect. RESULTS: Twenty-six observational
      studies and 6 randomized trials were identified. Using combination PDE-5
      inhibitor and prostaglandin analogues, 6/7 studies reported improvement in 6MWD,
      6/8 studies reported improvement in FC, 6/6 studies reported improvement in
      haemodynamics and 1 trial demonstrated improvement in QoL and time-to-clinical
      worsening. Using combination ERA and prostaglandin analogues, 4/6 studies and 1
      trial reported improvement in 6MWD, 3/3 studies and 1 trial reported improvement
      in FC, 4/5 studies and 1 trial reported improvement in PAP. Using combination ERA
      and PDE-5 inhibitor, 4/7 studies reported an improvement in 6MWD, and 2/6 report
      improvement in FC. CONCLUSION: The evidence suggests a beneficial effect of dual
      therapy in IPAH and SSc-PAH, particularly those who are deteriorating on
      monotherapy. Research should focus on subsets of patients to identify the optimal
      timing and combination of dual therapy.

PMID- 22366297
TI  - Upregulation of high-affinity GABA(A) receptors in cultured rat dorsal root
      ganglion neurons.
AB  - Despite evidence that high-affinity GABA(A) receptor subunit mRNA and protein are
      present in dorsal root ganglia (DRG), low-affinity currents dominate those
      detected in acutely dissociated DRG neurons in vitro. This observation raises the
      possibility that high-affinity receptors are normally trafficked out of the DRG
      toward central and peripheral terminals. We therefore hypothesized that with time
      in culture, there would be an increase in high-affinity GABA(A) currents in DRG
      neurons. To test this hypothesis, we studied dissociated DRG neurons 2 h (acute)
      and 24 h (cultured) after plating with whole-cell patch-clamp techniques, Western
      blot, and semiquantitative reverse transcriptase polymerase chain reaction (sqRT
      PCR) analysis. GABA(A) current density increases dramatically with time in
      culture in association with the emergence of two persistent currents with EC50's
      of 0.25+/-0.01 MUM and 3.2+/-0.02 MUM for GABA activation. In a subpopulation of
      neurons, there was also an increase in the potency of GABA activation of the
      transient current from an EC50 of 78.16+/-10.1 MUM to 9.56+/-1.3 MUM with time in
      culture. A fraction of the high-affinity current was potentiated by delta-subunit
      agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP). delta-subunit
      immunoreactivity was largely restricted to the cytosolic fraction in acute, but
      the membrane fraction in cultured, DRG neurons, with no detectable change in
      delta-subunit mRNA. However, the emergence of a high-affinity current blocked by
      THIP and insensitive to bicuculline was detected in a subpopulation of cultured
      neurons as well in association with an increase in rho2- and rho3-subunit mRNA in
      cultured DRG neurons. Our results suggest that high-affinity delta-subunit
      containing GABA(A) receptors are normally trafficked out of the DRG where they
      are targeted to peripheral and central processes. They also highlight that the
      interpretation of data obtained from cultured DRG neurons should be made with
      caution.

PMID- 22366299
TI  - Affect, corporeality and the limits of belonging: breastfeeding in public in the
      contemporary UK.
AB  - The UK has some of the lowest breastfeeding duration rates in the industrialised
      world. This paper considers women's experiences breastfeeding in public as a
      factor in breastfeeding duration. Research is based on an analysis of: 11
      interviews and a 46-person survey of new mothers in Southampton, Hampshire; 180
      postings about breastfeeding in public on UK parenting website mumsnet; and a
      patent application for a 'portable lactation module'. I analyse these data
      through an engagement with the work of cultural theorist Sara Ahmed to argue that
      the 'limits of sociability' in public space in the UK can be marked through
      affective practice. This paper makes three unique contributions to scholarship.
      First, it increases understanding regarding an issue of direct importance to
      health policy by filling a gap in knowledge about women's experiences
      breastfeeding outside the home in the UK. Second, it contributes to the field of
      health geography by showing how affective environments can constrain health
      promoting behaviours. Third, it extends conceptual work in human geography more
      broadly through an analysis of the relationships between affect, embodiment and
      urban subjectivity.

PMID- 22366300
TI  - A comparison of two approaches to extracting Cryptosporidium DNA from human
      stools as measured by a real-time PCR assay.
AB  - Direct extraction of Cryptosporidium DNA from 46 stools by bead-beating,
      guanidine thiocyanate and silica purification provided slightly lower PCR
      positivity (93.5% vs. 100%) and higher threshold cycle values (mean 34.93 vs.
      28.03; P=0.00) than spin-column extraction from boiled, semi-purified oocyst
      suspensions. However, direct extraction is cheaper, and amenable to automation.

PMID- 22366301
TI  - A rapid microtiter plate serum bactericidal assay method for determining serum
      complement-mediated killing of Mannheimia haemolytica.
AB  - In this study, we describe a rapid microtiter serum bactericidal assay (RMSBA)
      that can be used to measure the functionality of immune sera. It quantifies
      bactericidal activity of immune sera in the presence of complement against a
      homologous bacterium, M. haemolytica in this case. There is high correlation
      between data from RMSBA and standard complement-mediated bacterial killing assay
      (r=0.756; p<0.0001). The RMSBA activity of sera can be generated in less than 5 h
      instead of overnight incubation. RMSBA costs substantially less in terms of time,
      labor, and resources and is highly reproducible.

PMID- 22366302
TI  - Structural determinants of MALT1 protease activity.
AB  - The formation of the CBM (CARD11-BCL10-MALT1) complex is pivotal for antigen
      receptor-mediated activation of the transcription factor NF-kappaB. Signaling is
      dependent on MALT1 (mucosa-associated lymphoid tissue lymphoma translocation
      protein 1), which not only acts as a scaffolding protein but also possesses
      proteolytic activity mediated by its caspase-like domain. It remained unclear how
      the CBM activates MALT1. Here, we provide biochemical and structural evidence
      that MALT1 activation is dependent on its dimerization and show that mutations at
      the dimer interface abrogate activity in cells. The unliganded protease presents
      itself in a dimeric yet inactive state and undergoes substantial conformational
      changes upon substrate binding. These structural changes also affect the
      conformation of the C-terminal Ig-like domain, a domain that is required for
      MALT1 activity. Binding to the active site is coupled to a relative movement of
      caspase and Ig-like domains. MALT1 binding partners thus may have the potential
      of tuning MALT1 protease activity without binding directly to the caspase domain.

PMID- 22366303
TI  - Prenatal diagnosis of partial trisomy 3q resulting from t(3;14) in a fetus with
      multiple anomalies including vermian hypoplasia.
AB  - While genetic origin of Dandy-Walker complex has not yet fully elucidated, the
      complex has been known to be associated with structural and chromosomal
      abnormalities. A partial trisomy 3q was also identified in patients with DWC. 3q
      duplication syndrome is defined as duplications of large parts of 3q, especially
      3q21-qter. Most cases with 3q duplication are diagnosed postnatally and the
      patients show typical features including various facial dysmorphisms, congenital
      heart defects, genitourinary malformations, and mental and growth retardation.
      Here we report a 28 year old nulliparous woman who was referred from the
      infertility clinic at 21 gestational weeks. Fetal ultrasonographic examination
      showed various abnormal findings including a ventricular septal defect,
      hydrocephalus, and hypoplasia of the cerebellar vermis. Fetal chromosome analysis
      was initially reported as 46,XY,der(14)(?::p11.2->qter). Array CGH followed by
      FISH allowed precise characterization of the der(14) chromosome and the initial
      karyotype of the fetus had been changed to 46,XY,add(14)(p11).ish
      der(14)t(3;14)(q26.1;p11)(tel3q+).arr 3q26.1q29(166249469-199288361)x3. Though
      further studies are required, gene clusters rather than a single gene might be
      responsible for the clinical features of the Dandy-Walker complex.

PMID- 22366304
TI  - Genome-wide analysis and environmental response profiling of the FK506-binding
      protein gene family in maize (Zea mays L.).
AB  - The FK506-binding proteins (FKBPs) belong to the peptidyl-prolyl cis/trans
      isomerase (PPIase) superfamily, and have been implicated in a wide spectrum of
      biological processes, including protein folding, hormone signaling, plant growth,
      and stress responses. Genome-wide structural and evolutionary analyses of the
      entire FKBP gene family have been conducted in Arabidopsis and rice. In the
      present study, a genome-wide analysis was performed to identify all maize FKBP
      genes. The availability of complete maize genome sequences allowed for the
      identification of 24 FKBP genes. Chromosomal locations in the maize genome were
      determined and the protein domain and motif organization of ZmFKBPs analyzed. The
      phylogenetic relationships between maize FKBPs were also assessed. The expression
      profiles of ZmFKBP genes were measured under different environmental conditions
      and revealed distinct ZmFKBP gene expression patterns under heat, cold, salt, and
      drought stress. These data not only contribute to a better understanding of the
      complex regulation of the maize FKBP gene family, but also provide evidence
      supporting the role of FKBPs in multiple signaling pathways involved in stress
      responses. This investigation may provide valuable information for further
      research on stress tolerance in plants and potential strategies for enhancing
      maize survival under stressful conditions.

PMID- 22366305
TI  - Lentivirus vector driven by polybiquitin C promoter without woodchuck
      posttranscriptional regulatory element and central polypurine tract generates low
      level and short-lived reporter gene expression.
AB  - Lentivirus (LV) encoding woodchuck posttranscriptional regulatory element (WPRE)
      and central polypurine tract (cPPT) driven by CMV promoter have been proven to
      act synergistically to increase both transduction efficiency and gene expression.
      However, the inclusion of WPRE and cPPT in a lentiviral construct may pose safety
      risks when administered to human. A simple lentiviral construct driven by an
      alternative promoter with proven extended duration of gene expression without the
      two regulatory elements would be free from the risks. In a non-viral gene
      delivery context, gene expression driven by human polybiquitin C (UbC) promoter
      resulted in higher and more persistent expression in mouse as compared to
      cytomegalovirus (CMV) promoter. In this study, we measured the efficiency and
      persistency of green fluorescent protein (GFP) reporter gene expression in cells
      transduced with LV driven by UbC (LV/UbC/GFP) devoid of the WPRE and cPPT in
      comparison to the established LV construct encoding WPRE and cPPT, driven by CMV
      promoter (LV/CMV/GFP). However, we found that LV/UbC/GFP was inferior to
      LV/CMV/GFP in many aspects: (i) the titer of virus produced; (ii) the levels of
      reporter gene expression when MOI value was standardized; and (iii) the
      transduction efficiency in different cell types. The duration of reporter gene
      expression in selected cell lines was also determined. While the GFP expression
      in cells transduced with LV/CMV/GFP persisted throughout the experimental period
      of 14 days, expression in cells transduced with LV/UbC/GFP declined by day 2 post
      transduction. In summary, the LV driven by the UbC promoter without the WPRE and
      cPPT does not exhibit enhanced or durable transgene expression.

PMID- 22366306
TI  - Congenital heart defect and mental retardation in a patient with a 13q33.1-34
      deletion.
AB  - 13q deletion syndrome is a rare genetic disorder caused by deletions of the long
      arm of chromosome 13. Patients with 13q deletion display a variety of phenotypic
      features. We describe a one-year-old female patient with congenital heart defects
      (CHD), facial anomalies, development and mental retardation. We identified a
      12.75Mb deletion in chromosome region 13q33.1-34 with high resolution SNP Array
      (Human660W-Quad, Illumina, USA). This chromosome region contains about 55 genes,
      including EFNB2, ERCC5, VGCNL1, F7, and F10. Comparing our findings with
      previously reported 13q deletion patients with congenital heart defects, we
      propose that the 13q33.1-34 deletion region might contain key gene(s) associated
      with cardiac development. Our study also identified a subclinical deficiency of
      Factors VII and X in our patient with Group 3 of 13q deletion syndrome.

PMID- 22366307
TI  - The membrane interactions of antimicrobial peptides revealed by solid-state NMR
      spectroscopy.
AB  - Solid-state NMR spectroscopic techniques provide valuable information about the
      structure, dynamics and topology of membrane-inserted polypeptides. In particular
      antimicrobial peptides (or 'host defence peptides') have early on been
      investigated by solid-state NMR spectroscopy and many technical innovations in
      this domain have been developed with the help of these compounds when
      reconstituted into oriented phospholipid bilayers. Using solid-state NMR
      spectroscopy it could be shown for the first time that magainins or derivatives
      thereof exhibit potent antimicrobial activities when their cationic amphipathic
      helix is oriented parallel to the bilayer surface, a configuration found in later
      years for many other linear cationic amphipathic peptides. In contrast
      transmembrane alignments or lipid-dependent tilt angles have been found for more
      hydrophobic sequences such as alamethicin or beta-hairpin antimicrobials. This
      review presents various solid-state NMR approaches and develops the basic
      underlying concept how angular information can be obtained from oriented samples.
      It is demonstrated how this information is used to calculate structures and
      topologies of peptides in their native liquid-disordered phospholipid bilayer
      environment. Special emphasis is given to discuss which NMR parameters provide
      the most complementary information, the minimal number of restraints needed and
      the effect of motions on the analysis of the NMR spectra. Furthermore, recent
      (31)P and (2)H solid-state NMR measurements of lipids are presented including
      some unpublished data which aim at investigating the morphological and structural
      changes of oriented or non-oriented phospholipids. Finally the structural models
      that have been proposed for the mechanisms of action of these peptides will be
      presented and discussed in view of the solid-state NMR and other biophysical
      experiments.

PMID- 22366308
TI  - EGFR and myosin II inhibitors cooperate to suppress EGFR-T790M-mutant NSCLC
      cells.
AB  - An acquired mutation (T790M) in the epidermal growth factor receptor (EGFR)
      accounts for half of all relapses in non-small cell lung cancer (NSCLC) patients
      who initially respond to EGFR kinase inhibitors. In this study, we demonstrated
      for the first time that EGFR-T790M interacts with the cytoskeletal components,
      myosin heavy chain 9 (MYH9) and beta-actin, in the nucleus of H1975 cells
      carrying the T790M-mutant EGFR. The interactions of EGFR with MYH9 and beta-actin
      were reduced in the presence of blebbistatin, a specific inhibitor for the MYH9
      beta-actin interaction, suggesting that the EGFR interaction with MYH9 and beta
      actin is affected by the integrity of the cytoskeleton. These physical
      interactions among MYH9, beta-actin, and EGFR were also impaired by CL-387,785, a
      kinase inhibitor for EGFR-T790M. Furthermore, CL-387,785 and blebbistatin
      interacted in a synergistic fashion to suppress cell proliferation and induce
      apoptosis in H1975 cells. The combination of CL-387,785 and blebbistatin enhanced
      the down-regulation of cyclooxygenase-2 (COX-2), a transcriptional target of
      nuclear EGFR. Overall, our findings demonstrate that disrupting EGFR interactions
      with the cytoskeletal components enhanced the anti-cancer effects of CL-387,785
      against H1975 cells, suggesting a novel therapeutic approach for NSCLC cells that
      express the drug-resistant EGFR-T790M.

PMID- 22366309
TI  - Orphan drug development: an economically viable strategy for biopharma R&D.
AB  - Orphan drug incentives have stimulated research into diseases with significant
      unmet medical need. Although the targeting of orphan diseases is seen by industry
      as an attractive strategy, there are limited economic data available to support
      its use. In this paper we show that the revenue-generating potential of orphan
      drugs is as great as for non-orphan drugs, even though patient populations for
      rare diseases are significantly smaller. Moreover, we suggest that orphan drugs
      have greater profitability when considered in the full context of developmental
      drivers including government financial incentives, smaller clinical trial sizes,
      shorter clinical trial times and higher rates of regulatory success. The data
      support the targeting of rare diseases as an important component of a successful
      biopharma R&D strategy.

PMID- 22366310
TI  - Dietary administration of chitooligosaccharides to enhance growth, innate immune
      response and disease resistance of Trachinotus ovatus.
AB  - The present study was conducted to investigate the effects of dietary
      chitooligosaccharides (COS) supplementation on the innate immune response and
      protection against Vibrio harveyi infection in Trachinotus ovatus. A basal diet
      was supplemented with 0.0 (control), 2.0, 4.0 and 6.0 g COS kg(-1) to formulate
      four experimental diets. Each diet was randomly allocated to triplicate groups of
      fish in floating sea cages (1.5 * 1.0 * 2.0 m), and each cage was stocked with 80
      fish (initial average weight 10.8 +/- 0.05 g). After 8 weeks of feeding trial,
      Both the final weight and specific growth rate (SGR) significantly increased with
      increasing dietary COS levels up to 4.0 g kg(-1), whereas there were no
      significant differences for COS levels from 4.0 to 6.0 g kg(-1). A decreased feed
      conversion ratio (FCR) was observed with increasing dietary COS levels. The total
      leukocyte counts (WBC), differential leukocyte counts, respiratory burst
      activity, lysozyme and superoxide dismutase (SOD) activity were significantly
      increased with the increased levels of dietary COS (P < 0.05), and reached a
      maximum at level of 4.0 g kg(-1) COS. There were no significant differences in
      those immunological parameters between 4.0 and 6.0 g kg(-1) COS. Moreover, the
      dietary COS supplementation groups also exhibited a decrease in the cumulative
      symptom rates compared to the controls when challenged with V. harveyi. These
      results indicated that dietary intake containing COS could enhance the immune
      responses of fish and improve its resistance to infection by V. harveyi.
      Especially supplementation with 4.0 g kg(-1) COS to the fish for 56 days showed
      considerable improvement in the growth, survival and immune response of the fish.

PMID- 22366311
TI  - Effect of dietary vitamin C on the growth performance and innate immunity of
      juvenile cobia (Rachycentron canadum).
AB  - This study was conducted to evaluate the effects of dietary vitamin C on growth
      performance, hematologic parameters and innate immune responses in juvenile
      cobia, Rachycentron canadum. Seven practical diets were formulated to contain 0.0
      (as the basal diet), 13.6, 27.2, 54.4, 96.6, 193.4 and 386.5 mg ascorbic acid
      equivalent kg(-1) diet. Each diet was fed to triplicate groups of juvenile cobia
      with initial body weight of 5.5 g in 500-L cylindrical fiberglass tank. The
      results of 8 weeks feeding trial showed that typical vitamin C-deficient signs
      such as spinal deformation and body nigrescence were observed in the fish fed the
      basal diet. Fish fed the basal diet had significantly lower weight gain, specific
      growth rate (SGR), protein efficiency ratio (PER) and feed efficiency (FE) than
      those fed the diets supplemented with vitamin C, but no significant differences
      were observed among diets supplemented with vitamin C. However, survival rate was
      significantly affected by the dietary vitamin C levels, fish fed the basal diet
      had lower survival rate than those fed the diets supplemented with vitamin C. The
      ascorbic acid concentration in liver was correlated positively with the dietary
      vitamin C levels, however, the thiobarbituric acid reactive substances (TBARS)
      concentrations in liver was not significantly affected by the dietary vitamin C
      levels, although, fish fed the basal diet had the highest TBARS values among all
      treatments. The activities of serum lysozyme, superoxide dismutase (SOD),
      alkaline phophatase (AKP) and total immunoglobulin (Ig) were significantly
      influenced by the dietary vitamin C levels, fish fed the basal diet had lower
      lysozyme, SOD, AKP and total Ig than those fed diets supplemented with vitamin C.
      The serum glucose and triglyceride concentrations were significantly affected by
      the dietary vitamin C levels. Fish fed the basal diet had lower red blood cell
      and hemoglobin values than those fed the vitamin C supplemented diets. The
      challenge experiment with Vibrio harveyi showed that lower cumulative survival
      was in fish fed the unsupplemented diet, the cumulative survival were
      significantly increased with increase of the dietary ascorbic acid levels from
      13.6 to 96.6 mg kg(-1), while the cumulative survival reached plateau when
      dietary ascorbic acid levels increased from 96.6 to 386.5 mg kg(-1). These
      results indicated that dietary vitamin C did significantly influence on growth
      performance and immune response of juvenile cobia.

PMID- 22366312
TI  - Development of a quantitative assay to measure expression of transforming growth
      factor beta (TGF-beta) in Lost River sucker (Deltistes luxatus) and shortnose
      sucker (Chasmistes brevirostris) and evaluation of potential pitfalls in use with
      field-collected samples.
AB  - The Nature Conservancy is in the process of restoring the Williamson River Delta
      in an attempt to recreate important juvenile habitat for the endangered shortnose
      sucker Chasmistes brevirostris and the endangered Lost River sucker Deltistes
      luxatus. Measurement of TGF-beta mRNA expression level was one of the indicators
      chosen to evaluate juvenile sucker health during the restoration process. TGF
      beta mRNA expression level has been correlated with disease status in several
      laboratory studies and TGF-beta mRNA expression level has been used as a species
      specific indicator of immune status in field-based fish health assessments. We
      describe here the identification of TGF-beta and a possible splice variant from
      shortnose sucker and from Lost River sucker. The performance of a quantitative RT
      PCR assay to measure TGF-beta mRNA expression level was evaluated in field
      collected spleen and kidney tissue samples. The quality of extracted RNA was
      higher in tissues harvested in September compared to July and higher in tissues
      harvested at lower temperature compared to higher temperature. In addition, the
      expression level of both TGF-beta and 18S as assessed by qRT-PCR was higher in
      samples with higher quality RNA. TGF-beta mRNA expression was lower in kidney
      than in spleen in both Lost River sucker and shortnose sucker.

PMID- 22366313
TI  - Effects of different implant-abutment connections on micromotion and stress
      distribution: prediction of microgap formation.
AB  - OBJECTIVES: The aim of this study was to analyse micromotion and stress
      distribution at the connections of implants and four types of abutments: internal
      hexagonal, internal octagonal, internal conical and trilobe. METHODS: A three
      dimensional (3D) model of the left posterior mandible was reconstructed from
      medical datasets. Four dental implant systems were designed and analysed
      independently in a virtual simulation of a first molar replacement. Material
      properties, contact properties, physiological loading and boundary conditions
      were assigned to the 3D model. Statistical analysis was performed using one-way
      analysis of variance (ANOVA) with a 95% confidence interval and Tukey's Honestly
      Significant Difference (HSD) multiple comparison test. RESULTS: The internal
      hexagonal and octagonal abutments produced similar patterns of micromotion and
      stress distribution due to their regular polygonal design. The internal conical
      abutment produced the highest magnitude of micromotion, whereas the trilobe
      connection showed the lowest magnitude of micromotion due to its polygonal
      profile. CONCLUSIONS: Non-cylindrical abutments provided a stable locking
      mechanism that reduced micromotion, and therefore reduced the occurrence of
      microgaps. However, stress tends to concentrate at the vertices of abutments,
      which could lead to microfractures and subsequent microgap formation.

PMID- 22366314
TI  - Immobilized smart RNA on graphene oxide nanosheets to specifically recognize and
      adsorb trace peptide toxins in drinking water.
AB  - The contaminations of peptide toxins in drinking water lead directly to sickness
      and even death in both humans and animals. A smart RNA as aptamer is covalently
      immobilized on graphene oxide to form a polydispersed and stable RNA-graphene
      oxide nanosheet. RNA-graphene oxide nanosheets can resist nuclease and natural
      organic matter, and specifically adsorb trace peptide toxin (microcystin-LR) in
      drinking water. The adsorption data fit the pseudo-second-order kinetics and the
      Langmuir isotherm model. The adsorption capacity of RNA-graphene oxide nanosheets
      decreases at extreme pH, temperature, ionic strength and natural organic matter,
      but it is suitable to adsorb trance pollutants in contaminated drinking water.
      Compared with other chemical and biological sorbents, RNA-graphene oxide
      nanosheets present specific and competitive adsorption, and are easily
      synthesized and regenerated. Aptamer (RNA) covalently immobilized on graphene
      oxide nanosheets is a potentially useful tool in recognizing, enriching and
      separating small molecules and biomacromolecules in the purification of
      contaminated water and the preparation of samples.

PMID- 22366315
TI  - Simple synthesis of Ni-containing ordered mesoporous carbons and their
      adsorption/desorption of methylene orange.
AB  - A simple route has been developed to synthesize magnetic Ni-containing ordered
      mesoporous carbons (Ni/OMCs) without using a solvent for dissolving carbon
      precursor or magnetic source. The adsorption and desorption of methylene orange
      (MO) on the obtained Ni/OMCs were investigated. The effects of Ni(NO(3))(2)
      loading amount and carbonization temperature on the morphologies, the structural
      parameters and magnetic properties of these Ni/OMCs were evaluated by X-ray
      diffraction(XRD), N(2) sorption analysis, transmission electron microscopy(TEM)
      and physical property measurements. With the increase of Ni(NO(3))(2) loading
      amount, the ordering of the mesoporous structures, the specific surface area and
      the total pore volumes of Ni/OMCs decreased, but the pore diameters of Ni/OMCs
      and the sizes of Ni particle increased. The saturation magnetization strength
      could be easily adjusted by varying the amount of Ni(NO(3))(2). The specific
      surface area and total pore volumes decreased with the increasing of
      carbonization temperature. The size of Ni particle was the biggest at 750 degrees
      C. The adsorption of MO into Ni/OMCs followed the Sips adsorption model. More
      interestingly, a simple equation was obtained and was proved to well fit the
      desorption behavior of MO on Ni/OMCs. The values for the relative fitted
      parameters were obtained and the physical meanings of the parameters were well
      defined.

PMID- 22366316
TI  - Urine as a CO2 absorbent.
AB  - The aim of this work was to investigate the effect of urine on the absorption of
      greenhouse gases such as CO(2). Human urine diluted with olive-oil-mill
      wastewaters (OMW) could be used to capture CO(2) from flue gas of coal-fired
      power plant and convert CO(2) emissions into valuable fertilizers (mainly,
      NH(4)HCO(3)) that can enhance CO(2) sequestration into soil and subsoil layers.
      Thus, the CO(2) emissions could be reduced between 0.1 and 1%. The proposed
      strategy requires further research to increase CO(2) absorption and assess the
      risks associated with wastewater reuse and xenobiotics in the agroecological
      environment.

PMID- 22366317
TI  - Peptide tag forming a rapid covalent bond to a protein, through engineering a
      bacterial adhesin.
AB  - Protein interactions with peptides generally have low thermodynamic and
      mechanical stability. Streptococcus pyogenes fibronectin-binding protein FbaB
      contains a domain with a spontaneous isopeptide bond between Lys and Asp. By
      splitting this domain and rational engineering of the fragments, we obtained a
      peptide (SpyTag) which formed an amide bond to its protein partner (SpyCatcher)
      in minutes. Reaction occurred in high yield simply upon mixing and amidst diverse
      conditions of pH, temperature, and buffer. SpyTag could be fused at either
      terminus or internally and reacted specifically at the mammalian cell surface.
      Peptide binding was not reversed by boiling or competing peptide. Single-molecule
      dynamic force spectroscopy showed that SpyTag did not separate from SpyCatcher
      until the force exceeded 1 nN, where covalent bonds snap. The robust reaction
      conditions and irreversible linkage of SpyTag shed light on spontaneous
      isopeptide bond formation and should provide a targetable lock in cells and a
      stable module for new protein architectures.

PMID- 22366318
TI  - Dynamic denitrosylation via S-nitrosoglutathione reductase regulates
      cardiovascular function.
AB  - Although protein S-nitrosylation is increasingly recognized as mediating nitric
      oxide (NO) signaling, roles for protein denitrosylation in physiology remain
      unknown. Here, we show that S-nitrosoglutathione reductase (GSNOR), an enzyme
      that governs levels of S-nitrosylation by promoting protein denitrosylation,
      regulates both peripheral vascular tone and beta-adrenergic agonist-stimulated
      cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR
      deficient mice exhibited reduced peripheral vascular tone and depressed beta
      adrenergic inotropic responses that were associated with impaired beta-agonist
      induced denitrosylation of cardiac ryanodine receptor 2 (RyR2), resulting in
      calcium leak. These results indicate that systemic hemodynamic responses
      (vascular tone and cardiac contractility), both under basal conditions and after
      adrenergic activation, are regulated through concerted actions of NO
      synthase/GSNOR and that aberrant denitrosylation impairs cardiovascular function.
      Our findings support the notion that dynamic S-nitrosylation/denitrosylation
      reactions are essential in cardiovascular regulation.

PMID- 22366319
TI  - Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A.
AB  - MicroRNA-125b (miR-125b) is up-regulated in patients with leukemia.
      Overexpression of miR-125b alone in mice causes a very aggressive, transplantable
      myeloid leukemia. Before leukemia, these mice do not display elevation of white
      blood cells in the spleen or bone marrow; rather, the hematopoietic compartment
      shows lineage-skewing, with myeloid cell numbers dramatically increased and B
      cell numbers severely diminished. miR-125b exerts this effect by up-regulating
      the number of common myeloid progenitors while inhibiting development of pre-B
      cells. We applied a miR-125b sponge loss of function system in vivo to show that
      miR-125b physiologically regulates hematopoietic development. Investigating the
      mechanism by which miR-125b regulates hematopoiesis, we found that, among a panel
      of candidate targets, the mRNA for Lin28A, an induced pluripotent stem cell gene,
      was most repressed by miR-125b in mouse hematopoietic stem and progenitor cells.
      Overexpressing Lin28A in the mouse hematopoietic system mimicked the phenotype
      observed on inhibiting miR-125b function, leading to a decrease in hematopoietic
      output. Relevant to the miR-125b overexpression phenotype, we also found that
      knockdown of Lin28A led to hematopoietic lineage-skewing, with increased myeloid
      and decreased B-cell numbers. Thus, the miR-125b target Lin28A is an important
      regulator of hematopoiesis and a primary target of miR-125b in the hematopoietic
      system.

PMID- 22366320
TI  - Anti-tick monoclonal antibody applied by artificial capillary feeding in
      Rhipicephalus (Boophilus) microplus females.
AB  - The tick Rhipicephalus microplus is an ectoparasite harmful to livestock, a
      vector of disease agents that affects meat and milk production. However,
      resistance to acaricides reflects the need for alternative tick control methods,
      among which vaccines have gained increasing relevance. In this scenario,
      monoclonal antibodies can be used to identify and characterize antigens that can
      be used as vaccine immunogens. Capillary tube artificial feeding of partially
      engorged R. microplus females with monoclonal antibodies against proteins from
      the gut of tick were used to test the effects of immunoglobulins in the
      physiology of the parasite. The results of artificial feeding showed that female
      ticks over 25mg and under 60 mg in weight performed better in the artificial
      feeding process, with a 94-168% weight increase after 24h of feeding. Results
      showed that artificial feeding of ticks proved to be a viable technique to study
      the effects of antibodies or drugs in the physiology of the parasite. One
      monoclonal antibody (BrBm2) induced decreased oviposition. Moreover, the antigen
      recognized by BrBm2 was identified as a 27-kDa protein and immunolabeled on
      digestive vesicles membranes of digestive cells of partially and fully engorged
      females.

PMID- 22366321
TI  - Qualitative and quantitative reversed-phase high performance liquid
      chromatographic analysis of glycoprotein hormones in the presence of a large
      excess of human serum albumin.
AB  - The present work describes reversed-phase high performance liquid chromatographic
      methodologies (RP-HPLC) for the qualitative and quantitative analysis of the
      human glycoprotein hormones thyrotropin (hTSH), follitropin (hFSH),
      choriogonadotropin (hCG) and lutropin (hLH) in the presence of a large excess (up
      to 250:1) of human serum albumin (HSA). Chromatographic profiles with a good
      separation between the hormone and HSA were obtained by using a C4 column and
      specific gradient elution conditions for each hormone. Parameters such as
      resolution factor, tailing factor and relative retention time, were determined,
      and are useful for the evaluation of the quality of the separation obtained
      between the active pharmaceutical ingredient and the excipient present in the
      final formulation. The potential of each method for quantification of both HSA
      and the hormone was also demonstrated. Besides furnishing chromatographic
      quantifications that can substitute for in vivo bioassays and animal use, the
      chromatograms also provide a direct panorama of the quality and heterogeneity of
      the protein of interest.

PMID- 22366322
TI  - Development of a method for the determination of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol in urine of nonsmokers and smokers using liquid
      chromatography/tandem mass spectrometry.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an efficient biomarker of
      tobacco-specific carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
      The ability to monitor biomarker concentrations is very important in
      understanding potential cancer risk. An analytical method using molecularly
      imprinted polymer (MIP) column coupled with liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) for the determination of total NNAL in human urine was
      developed and validated. The combination of MIP column extraction and LC-MS/MS
      can provide a high sensitive and relatively simple analytical method. The limit
      of detection (LOD) was 0.30 pg/ml and analysis time was 6min. The method has been
      applied to urine samples of 36 nonsmokers and 207 smokers. NNAL was found to be
      significantly higher in the urine of smokers compared with nonsmokers. Compared
      with smokers with blended cigarettes, Chinese virginia cigarettes smokers had low
      urinary NNAL levels. There was a direct association between the 24-h mouth-level
      exposure of carcinogen NNK from cigarette smoking and the concentration of NNAL
      in the urine of smokers. However, there was not a positive correlation between
      urinary total NNAL levels in 24 h and tar. Total urinary NNAL is a valuable
      biomarker for monitoring exposure to carcinogenic NNK in smokers and in
      nonsmokers. A prediction model of cigarette smoke NNK and urinary average NNAL
      levels in 24 h was established (y=2.8987x-245.38, r2=0.9952, n=204).

PMID- 22366323
TI  - Methods to measure the binding of therapeutic monoclonal antibodies to the human
      Fc receptor FcgammaRIII (CD16) using real time kinetic analysis and flow
      cytometry.
AB  - Two different methods have been developed to measure the binding of therapeutic
      antibodies to the low affinity human Fc receptor FcgammaRIII (CD16). The first
      measures binding of antibody to recombinant soluble receptor by surface plasmon
      resonance and the second uses flow cytometry to measure antibody binding to cells
      which express the receptor. Both methods have been formatted as parallel line
      assays and show high levels of accuracy, precision and linearity, making them
      suitable for comparability, potency and stability assays. They are both readily
      able to detect structural differences such as glycosylation, which affect Fc
      receptor binding. The same approaches can be used to measure the binding of any
      antibody to any Fc receptor. These assays show greater internal precision and
      long-term reproducibility than traditional cell-based assays such as antibody
      dependent cell-mediated cytotoxicity. A combinational approach with a target
      binding might be appropriate for routine drug batch release as these assays are
      likely to be significantly more sensitive to small changes in drug structure or
      activity.

PMID- 22366324
TI  - Supercritical fluid chromatography for the enantioseparation of pharmaceuticals.
AB  - Chirality has a significant impact on drug discovery and development processes in
      the pharmaceutical industry. As the number of enantiopure drugs launched onto the
      market is yearly increasing, the need for fast and performant enantioseparation
      methods with minimal costs is becoming more compelling. In this context, sub- and
      supercritical fluid chromatography (SFC), being applicable at an analytical, as
      well as at a preparative scale is gaining more interest. In this review a
      practical overview is given of the different parameters that are important in
      supercritical fluid chromatographic separations. A comparison is made between the
      applicability for chiral separations of SFC and conventional high-performance
      liquid chromatography (HPLC), and illustrated by means of examples. Different
      aspects of method development and the upscaling feasibility in SFC are discussed.
      This review aims to give the reader a practical insight in the use of
      supercritical fluid chromatography for the chiral separation of pharmaceutical
      compounds.

PMID- 22366326
TI  - Altered ventral striatal activation during reward and punishment processing in
      premanifest Huntington's disease: a functional magnetic resonance study.
AB  - Recent research using various neuroimaging methods revealed the crucial role of
      the striatum concerning the neuropathology of Huntington's disease. Degenerative
      changes located in the basal ganglia are already observable in premanifest stages
      of Huntington's disease (pre-HD), i.e., before the onset of manifest motor
      symptoms. Although the impact of the striatum on reward and punishment processing
      is well-established in healthy subjects, these processes have not been
      investigated in manifest and premanifest HD subjects using functional magnetic
      resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to
      investigate valence discrimination in terms of rewarding and punishing cues in 30
      pre-HD and 15 healthy subjects. According to the probability of disease onset
      within the next 5 years, pre-HD subjects were categorized as either near to motor
      symptom onset (pre-HD(near); 9.9 [+/-2.91] years to onset) or far from manifest
      disease onset (pre-HD(far); 23.49 [+/-5.99] years to onset). Compared to pre
      HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal
      differentiation between reward and control anticipation located in the left
      ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant
      ventral striatal discrimination between punishing and control cues was detected
      in pre-HD(near) subjects. In the present study, we demonstrated for the first
      time significant differences in valence discrimination in pre-HD(near) subjects
      compared to pre-HD(far) subjects and healthy controls. Altered reward and
      punishment processing could therefore reflect a motivational deficit that may
      contribute to the pathogenesis of Huntington's disease.

PMID- 22366325
TI  - Susceptibility to a parkinsonian toxin varies during primate development.
AB  - Symptoms of Parkinson's disease typically emerge later in life when loss of
      nigrostriatal dopamine neuron function exceeds the threshold of compensatory
      mechanisms in the basal ganglia. Although nigrostriatal dopamine neurons are lost
      during aging, in Parkinson's disease other detrimental factors must play a role
      to produce greater than normal loss of these neurons. Early development has been
      hypothesized to be a potentially vulnerable period when environmental or genetic
      abnormalities may compromise central dopamine neurons. This study uses a specific
      parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to
      probe the relative vulnerability of nigrostriatal dopamine neurons at different
      stages of primate development. Measures of dopamine, homovanillic acid, 1-methyl
      pyridinium concentrations and tyrosine hydroxylase immunoreactive neurons
      indicated that at mid-gestation dopamine neurons are relatively vulnerable to
      MPTP, whereas later in development or in the young primate these neurons are
      resistant to the neurotoxin. These studies highlight a potentially greater risk
      to the fetus of exposure during mid-gestation to environmental agents that cause
      oxidative stress. In addition, the data suggest that uncoupling protein-2 may be
      a target for retarding the progressive loss of nigrostriatal dopamine neurons
      that occurs in Parkinson's disease and aging.

PMID- 22366327
TI  - In vivo intermittent hypoxia elicits enhanced expansion and neuronal
      differentiation in cultured neural progenitors.
AB  - In vitro exposure of neural progenitor cell (NPC) populations to reduced O(2)
      (e.g. 3% versus 20%) can increase their proliferation, survival and neuronal
      differentiation. Our objective was to determine if an acute (<1hr), in vivo
      exposure to intermittent hypoxia (AIH) alters expansion and/or differentiation of
      subsequent in vitro cultures of NPC from the subventricular zone (SVZ). Neonatal
      C57BL/6 mice (postnatal day 4) were exposed to an AIH paradigm (20*1 minute;
      alternating 21% and 10% O(2)). Immediately after AIH, SVZ tissue was isolated and
      NPC populations were cultured and assayed either as neurospheres (NS) or as
      adherent monolayer cells (MASC). AIH markedly increased the capacity for
      expansion of cultured NS and MASC, and this was accompanied by increases in a
      proliferation maker (Ki67), MTT activity and hypoxia-inducible factor-1alpha (HIF
      1alpha) signaling in NS cultures. Peptide blockade experiments confirmed that
      proteins downstream of HIF-1alpha are important for both proliferation and
      morphological changes associated with terminal differentiation in NS cultures.
      Finally, immunocytochemistry and Western blotting experiments demonstrated that
      AIH increased expression of the neuronal fate determination transcription factor
      Pax6 in SVZ tissue, and this was associated with increased neuronal
      differentiation in cultured NS and MASC. We conclude that in vivo AIH exposure
      can enhance the viability of subsequent in vitro SVZ-derived NPC cultures. AIH
      protocols may therefore provide a means to "prime" NPC prior to transplantation
      into the injured central nervous system.

PMID- 22366329
TI  - Release and transportation of Hedgehog molecules.
AB  - Secretion of the Hedgehog morphogen induces different cell fates over the short
      and long ranges during developmental patterning. Mature Hedgehog carries
      hydrophobic palmitic acid and cholesterol modifications essential for its correct
      spread. The long-range activity of Hedgehog raises questions about how a dually
      lipidated protein can spread in the hydrophilic environment of the extracellular
      space. There is compelling experimental evidence in favour of the existence of
      several different carriers for Hedgehog transportation, via very different
      routes. This suggests that different accessory proteins and cellular machineries
      may be involved in the specific release of Hedgehog. I suggest that Hh carriers
      may work in parallel within a given cell and that developmental context may
      condition the choice of Hh carrier in secreting cells.

PMID- 22366328
TI  - VEGF signaling inside vascular endothelial cells and beyond.
AB  - Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key
      regulator of vascular development and function in health and disease. VEGF is a
      secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors
      on the plasma membrane, inducing their dimerization, activation and assembly of a
      membrane-proximal signaling complex. Recent studies have revealed that many key
      events of VEGFR signaling occur inside the endothelial cell and are regulated by
      endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules,
      including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR
      endocytosis and trafficking. VEGF signaling is increasingly recognized for its
      roles outside of the vascular system, notably during neural development, and
      blood vessels regulate epithelial branching morphogenesis. We review here recent
      advances in our understanding of VEGF signaling and its biological roles.

PMID- 22366330
TI  - Cortical surface registration using spherical thin-plate spline with sulcal lines
      and mean curvature as features.
AB  - Analysis of cortical patterns requires accurate cortical surface registration.
      Many researchers map the cortical surface onto a unit sphere and perform
      registration of two images defined on the unit sphere. Here we have developed a
      novel registration framework for the cortical surface based on spherical thin
      plate splines. Small-scale composition of spherical thin-plate splines was used
      as the geometric interpolant to avoid folding in the geometric transform. Using
      an automatic algorithm based on anisotropic skeletons, we extracted seven sulcal
      lines, which we then incorporated as landmark information. Mean curvature was
      chosen as an additional feature for matching between spherical maps. We employed
      a two-term cost function to encourage matching of both sulcal lines and the mean
      curvature between the spherical maps. Application of our registration framework
      to fifty pairwise registrations of T1-weighted MRI scans resulted in improved
      registration accuracy, which was computed from sulcal lines. Our registration
      approach was tested as an additional procedure to improve an existing surface
      registration algorithm. Our registration framework maintained an accurate
      registration over the sulcal lines while significantly increasing the cross
      correlation of mean curvature between the spherical maps being registered.

PMID- 22366331
TI  - Use of statistical tools to evaluate the reductive dechlorination of high levels
      of TCE in microcosm studies.
AB  - A large, multi-laboratory microcosm study was performed to select amendments for
      supporting reductive dechlorination of high levels of trichloroethylene (TCE)
      found at an industrial site in the United Kingdom (UK) containing dense non
      aqueous phase liquid (DNAPL) TCE. The study was designed as a fractional
      factorial experiment involving 177 bottles distributed between four industrial
      laboratories and was used to assess the impact of six electron donors,
      bioaugmentation, addition of supplemental nutrients, and two TCE levels (0.57 and
      1.90 mM or 75 and 250 mg/L in the aqueous phase) on TCE dechlorination.
      Performance was assessed based on the concentration changes of TCE and reductive
      dechlorination degradation products. The chemical data was evaluated using
      analysis of variance (ANOVA) and survival analysis techniques to determine both
      main effects and important interactions for all the experimental variables during
      the 203-day study. The statistically based design and analysis provided powerful
      tools that aided decision-making for field application of this technology. The
      analysis showed that emulsified vegetable oil (EVO), lactate, and methanol were
      the most effective electron donors, promoting rapid and complete dechlorination
      of TCE to ethene. Bioaugmentation and nutrient addition also had a statistically
      significant positive impact on TCE dechlorination. In addition, the microbial
      community was measured using phospholipid fatty acid analysis (PLFA) for
      quantification of total biomass and characterization of the community structure
      and quantitative polymerase chain reaction (qPCR) for enumeration of
      Dehalococcoides organisms (Dhc) and the vinyl chloride reductase (vcrA) gene. The
      highest increase in levels of total biomass and Dhc was observed in the EVO
      microcosms, which correlated well with the dechlorination results.

PMID- 22366332
TI  - Age effects on the P300 potential and the corresponding fMRI BOLD-signal.
AB  - Age has been reported to influence amplitude and latency of the P300 potential.
      Nevertheless, it is not yet fully understood which brain regions are responsible
      for these effects. The aim of this study was to investigate age-effects on the
      P300 potential and the simultaneously acquired BOLD signal of functional MRI. 32
      healthy male subjects were investigated using an auditory oddball paradigm. The
      functional MRI data were acquired in temporal synchrony to the task. The evoked
      potential data were recorded during the intervals in between MR image
      acquisitions in order to reduce the influence of the scanner noise on the
      presentation of the tones and to reduce gradient artifacts. The age-effects were
      calculated by means of regression analyses. In addition, brain regions modulated
      by the task-induced amplitude variation of the P300 were identified (single trial
      analysis). The results indicated an age effect on the P300 amplitude. Younger
      subjects demonstrated increased parietal P300 amplitudes and increased BOLD
      responses in a network of brain regions including the anterior and posterior
      cingulate cortex, the insula, the temporo-parietal junction, the superior
      temporal gyrus, the caudate body, the amygdala and the parahippocampal gyrus.
      Single trial coupling of EEG and fMRI indicated that P300 amplitudes were
      predominantly associated with neural responses in the anterior cingulate cortex,
      the putamen and temporal brain areas. Taken together, the results indicate
      diminished neural responses in older compared to younger subjects especially in
      frontal, temporo-parietal and subcortical brain regions.

PMID- 22366333
TI  - Decoding covert spatial attention using electrocorticographic (ECoG) signals in
      humans.
AB  - This study shows that electrocorticographic (ECoG) signals recorded from the
      surface of the brain provide detailed information about shifting of visual
      attention and its directional orientation in humans. ECoG allows for the
      identification of the cortical areas and time periods that hold the most
      information about covert attentional shifts. Our results suggest a transient
      distributed fronto-parietal mechanism for orienting of attention that is
      represented by different physiological processes. This neural mechanism encodes
      not only whether or not a subject shifts their attention to a location, but also
      the locus of attention. This work contributes to our understanding of the
      electrophysiological representation of attention in humans. It may also
      eventually lead to brain-computer interfaces (BCIs) that optimize user
      interaction with their surroundings or that allow people to communicate choices
      simply by shifting attention to them.

PMID- 22366334
TI  - The Human Connectome Project: a data acquisition perspective.
AB  - The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize
      brain connectivity and function and their variability in healthy adults. This
      review summarizes the data acquisition plans being implemented by a consortium of
      HCP investigators who will study a population of 1200 subjects (twins and their
      non-twin siblings) using multiple imaging modalities along with extensive
      behavioral and genetic data. The imaging modalities will include diffusion
      imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and
      T2-weighted MRI for structural and myelin mapping, plus combined
      magnetoencephalography and electroencephalography (MEG/EEG). Given the importance
      of obtaining the best possible data quality, we discuss the efforts underway
      during the first two years of the grant (Phase I) to refine and optimize many
      aspects of HCP data acquisition, including a new 7T scanner, a customized 3T
      scanner, and improved MR pulse sequences.

PMID- 22366335
TI  - Sub-chronic treatment with pioglitazone exerts anti-convulsant effects in
      pentylenetetrazole-induced seizures of mice: The role of nitric oxide.
AB  - OBJECTIVES: Pioglitazone delayed the development of seizure responses and
      shortened the duration of convulsion of genetically epileptic EL mice. The anti
      epileptic effect of pioglitazone was attributed partly through the reduction of
      inflammatory responses and preventing apoptosis. There are also some reports
      showing that some pioglitazone effects mediate through nitric oxide. In this
      study we evaluated sub-chronic pioglitazone effects in two models of intravenous
      and intraperitoneal pentylenetetrazole-induced clonic seizures in mice. MATERIALS
      AND METHODS: Different doses of pioglitazone were administered orally for 10 days
      in different groups of male mice. L-NAME, a non selective inhibitor of nitric
      oxide synthase, aminoguanidine, a selective inhibitor of inducible nitric oxide
      synthase, or L-arginine, a nitric oxide donor, was administered acutely or sub
      chronically to evaluate the role of nitric oxide in pioglitazone anti-seizure
      effects. RESULTS: We demonstrated that sub-chronic administration of pioglitazone
      exerted anti-convulsant effects in both models of intravenous and intraperitoneal
      pentylenetetrazole. Acute and sub-chronic pre-administration of L-NAME prevented
      the anti-convulsant effect of pioglitazone in both models of intravenous and
      intraperitoneal pentylenetetrazole. Aminoguanidine did not alter the anti
      convulsant effect of pioglitazone in two models of intravenous and
      intraperitoneal pentylenetetrazole. Both acute and sub-chronic pre-treatment of
      mice with L-arginine exerted anti-convulsant effect when administered with a non
      effective dose of pioglitazone in intraperitoneal method. In intravenous method,
      acute administration of L-arginine with a non-effective dose of pioglitazone
      enhanced the seizure clonic latency. CONCLUSION: Taken together, sub-chronic
      pioglitazone treatment exerts anti-convulsant effects in intravenous and
      intraperitoneal pentylenetetrazole-induced seizures of mice probably through
      induction of constitutive nitric oxide synthase.

PMID- 22366336
TI  - A changing landscape of physician quality reporting: analysis of patients' online
      ratings of their physicians over a 5-year period.
AB  - BACKGROUND: Americans increasingly post and consult online physician rankings,
      yet we know little about this new phenomenon of public physician quality
      reporting. Physicians worry these rankings will become an outlet for disgruntled
      patients. OBJECTIVE: To describe trends in patients' online ratings over time,
      across specialties, to identify what physician characteristics influence online
      ratings, and to examine how the value of ratings reflects physician quality.
      METHODS: We used data from RateMDs.com, which included over 386,000 national
      ratings from 2005 to 2010 and provided insight into the evolution of patients'
      online ratings. We obtained physician demographic data from the US Department of
      Health and Human Services' Area Resource File. Finally, we matched patients'
      ratings with physician-level data from the Virginia Medical Board and examined
      the probability of being rated and resultant rating levels. RESULTS: We estimate
      that 1 in 6 practicing US physicians received an online review by January 2010.
      Obstetrician/gynecologists were twice as likely to be rated (P < .001) as other
      physicians. Online reviews were generally quite positive (mean 3.93 on a scale of
      1 to 5). Based on the Virginia physician population, long-time graduates were
      more likely to be rated, while physicians who graduated in recent years received
      higher average ratings (P < .001). Patients gave slightly higher ratings to board
      certified physicians (P = .04), those who graduated from highly rated medical
      schools (P = .002), and those without malpractice claims (P = .1). CONCLUSION:
      Online physician rating is rapidly growing in popularity and becoming commonplace
      with no evidence that they are dominated by disgruntled patients. There exist
      statistically significant correlations between the value of ratings and physician
      experience, board certification, education, and malpractice claims, suggesting a
      positive correlation between online ratings and physician quality. However, the
      magnitude is small. The average number of ratings per physician is still low, and
      most rating variation reflects evaluations of punctuality and staff.
      Understanding whether they truly reflect better care and how they are used will
      be critically important.

PMID- 22366337
TI  - The cortisol awakening response is related to executive function in older age.
AB  - Changes in the cortisol awakening response (CAR) have been reportedly associated
      with older age and may reflect changes in cognitive performance. However
      methodological issues around adherence, in regard to careful timing of the CAR,
      suggest caution in drawing firm conclusions. More investigation is also needed
      regarding which cognitive domains may be most relevant. Executive Function (EF)
      is linked strongly to functioning of the frontal cortex, itself linked to
      cortisol secretion via regulation of the Hypothalamic Adrenocortical Axis. In
      this study, cortisol profiles, cognitive performance and adherence were carefully
      assessed in a sample of 50 older participants, aged 60-91 years (mean=74 years).
      Key aspects of EF were assessed using Form B of the standard Trail-making Test
      controlling for time taken to complete the simpler Trail-A form of the test.
      Strong associations between CAR profiles and EF were evident. Cortisol measures
      significantly predictive of superior EF-related performance in a regression
      analysis were: earlier peaking and greater magnitude of the CAR. Together these
      measures explained fully a quarter of all the variance in test performance
      (R(2)=0.25; F=7.90; df=2,47; p<.001). Cognitive tests of declarative memory,
      often linked to hippocampal functioning, were not associated with CAR profiles.
      We conclude that in a population of healthy older adults aspects of the CAR may
      be strongly, and perhaps with some degree of specificity, associated with that
      domain of cognitive functioning, EF, which seems to depend crucially on the
      integrity of frontal cortex circuitry.

PMID- 22366338
TI  - Peripheral biomarkers for individualizing immunosuppression in transplantation-
      regulatory T cells.
AB  - Regulatory T cells have gained much interest in the research community over the
      last 15 years. Here we give a short overview on the phenotype of Tregs, described
      subsets and their mode of action. We also summarize findings obtained within the
      last 4 years studying peripheral Tregs numbers and their function in solid organ
      transplant patients. Of special interest for the transplant community is whether
      such an analysis can be used to 1) identify pre-transplant "high risk" patients
      likely to develop severe acute rejection episodes shortly after transplantation,
      2) monitor drug-dependent reconstitution or changes of lymphocytes, 3) delineate
      and predict deterioration in graft function or rejections after transplantation
      and 4) identify potentially tolerant patients in whom immunosuppressive drugs can
      be safely withdrawn. The obtained results are very promising but mostly obtained
      by retrospective analysis on a limited number of patients. Thus, for the future
      collaborative efforts should be undertaken to initiate large prospective multi
      center trials in which the relevance of analyzing Tregs can be further validated.

PMID- 22366339
TI  - Isolation and characterization of transcription fidelity mutants.
AB  - Accurate transcription is an essential step in maintaining genetic information.
      Error-prone transcription has been proposed to contribute to cancer, aging,
      adaptive mutagenesis, and mutagenic evolution of retroviruses and
      retrotransposons. The mechanisms controlling transcription fidelity and the
      biological consequences of transcription errors are poorly understood. Because of
      the transient nature of mRNAs and the lack of reliable experimental systems, the
      identification and characterization of defects that increase transcription errors
      have been particularly challenging. In this review we describe novel genetic
      screens for the isolation of fidelity mutants in both Saccharomyces cerevisiae
      and Escherichia coli RNA polymerases. We obtained and characterized two distinct
      classes of mutants altering NTP misincorporation and transcription slippage both
      in vivo and in vitro. Our study not only validates the genetic schemes for the
      isolation of RNA polymerase mutants that alter fidelity, but also sheds light on
      the mechanism of transcription accuracy. This article is part of a Special Issue
      entitled: Chromatin in time and space.

PMID- 22366340
TI  - Insights into assembly and regulation of centromeric chromatin in Saccharomyces
      cerevisiae.
AB  - At the core of chromosome segregation is the centromere, which nucleates the
      assembly of a macromolecular kinetochore (centromere DNA and associated proteins)
      complex responsible for mediating spindle attachment. Recent advances in
      centromere research have led to identification of many kinetochore components,
      such as the centromeric-specific histone H3 variant, CenH3, and its interacting
      partner, Scm3. Both are essential for chromosome segregation and are
      evolutionarily conserved from yeast to humans. CenH3 is proposed to be the
      epigenetic mark that specifies centromeric identity. Molecular mechanisms that
      regulate the assembly of kinetochores at specific chromosomal sites to mediate
      chromosome segregation are not fully understood. In this review, we summarize the
      current literature and discuss results from our laboratory, which show that
      restricting the localization of budding yeast CenH3, Cse4, to centromeres and
      balanced stoichiometry between Scm3 and Cse4, contribute to faithful chromosome
      transmission. We highlight our findings that, similar to other eukaryotic
      centromeres, budding yeast centromeric histone H4 is hypoacetylated, and we
      discuss how altered histone acetylation affects chromosome segregation. This
      article is part of a Special Issue entitled: Chromatin in time and space.

PMID- 22366342
TI  - Taiwaniaquinoid and abietane quinone derivatives with trypanocidal activity
      against T. cruzi and Leishmania spp.
AB  - The in vitro leishmanicidal (Leishmania infantum and Leishmania braziliensis) and
      trypanocidal (Trypanosoma cruzi) activities of different compounds were
      evaluated. These compounds, of vegetal origin but synthesised in our laboratory,
      included five taiwaniaquinoid derivatives (S-567; S-569; S-589; S-602 and A-246)
      and one abietane quinone (P-1). The in vitro activity of the compounds on
      extracellular and intracellular forms of the two Leishmania species and T. cruzi
      was assayed. Infectivity and cytotoxicity tests for the Leishmania species were
      conducted on J774.2 macrophage cells using Glucantime as the reference drug. From
      all the compounds assayed, the derivatives P-1>S-567 were more active and less
      toxic than Glucantime. Infection rates and amastigote means indicated that these
      two compounds were the most active in both Leishmania species. In the case of T.
      cruzi, the best derivatives were P-1 and S-567, at the same levels as for the
      Leishmania species. These compounds exhibited the most potent anti-proliferative
      activity against the extracellular vector form (the epimastigote), the
      extracellular host form (the trypomastigote), and the intracellular host form
      (the amastigote), with lower toxicity than that of the reference drug
      Benznidazole. Metabolite excretion studies showed that alterations mainly at the
      level of the mitochondria may explain observed metabolic changes in succinate and
      acetate production, perhaps due to the disturbance of enzymes involved in sugar
      metabolism within the mitochondrion. The in vivo studies for T. cruzi provided
      results consistent with those found in vitro. No signs of toxicity were detected
      in mice treated with the compounds tested, and the parasitic charge was slightly
      lower than in the control. The effects of these two compounds were also
      demonstrated with the change in the anti-T. cruzi antibody levels during the
      chronic stage.

PMID- 22366343
TI  - Effects of fishing on parasitism in a sparid fish: contrasts between two areas of
      the Western Mediterranean.
AB  - This study addressed the impacts of fishing on the rates of parasitism using the
      sparid Boops boops as a model fish species. Using a large suite of parasite
      species in B. boops, with different life histories, transmission pathways and
      host specificity, we compared parasite diversity, prevalence, abundance and
      community structure at two Mediterranean localities in the Balearic Sea, Santa
      Pola Bay and the Gulf of Oran, that are characterised by a contrasting pattern of
      fishing of B. boops. A total of 360 fish were examined comprising nine distinct
      samples collected during the warm and the cold weather months. A total of 29
      parasite species were identified, with eight species in common for the two
      localities. Parasite component communities at Santa Pola Bay were more species
      rich and abundant than those at the Gulf of Oran and exhibited a different
      community structure. Of the eight common taxa used in the quantitative
      comparisons, five exhibited significant difference for prevalence between the two
      localities, four having substantially higher prevalence at Santa Pola and only
      one being more prevalent at the Gulf of Oran. Two specialist trematodes and the
      sparid generalist monogenean exhibited consistently higher prevalence and
      abundance at Santa Pola Bay than at the Gulf of Oran; the two specialists were
      also identified as key species for assigning individual fish to their locality of
      origin. The consistent differences in the richness, abundance and structure of
      parasite communities in B. boops from Santa Pola Bay and the Gulf of Oran may
      reflect the contrasting patterns of exploitation of the populations of this fish
      host at the two localities.

PMID- 22366341
TI  - Structure-toxicity relationship study of para-halogenated styrene analogues in
      CYP2E1 transgenic cells.
AB  - Styrene is one of the most important industrial intermediates consumed in the
      world and is mainly used as a monomer for reinforced plastics and rubber. Styrene
      has been found to be hepatotoxic and pneumotoxic in humans and experimental
      animals. The toxicity of styrene is suggested to be metabolism-dependent. Styrene
      7,8-oxide has been considered as the major metabolite responsible for styrene
      induced cytotoxicity. The objective of the study was to investigate the
      correlation between cytotoxicity of styrene and chemical and biochemical
      properties of the vinyl group of styrene by development of structure activity
      relationships (SAR). 4-Fluorostyrene, 4-chlorostyrene and 4-bromostyrene were
      selected for the SAR study. Cytotoxicity of styrene and the halogenated styrene
      derivatives with an order of 4-bromostyrene>4-chlorostyrene>4
      fluorostyrene~styrene was observed in CYP2E1 transgenic cells. Similar orders in
      the efficiency of the metabolism of styrene and the halogenated styrene analogues
      to their oxides and in the electrophilicity of the corresponding oxides were
      observed. Additionally, the order of the potency of cellular glutathione
      depletion and the degree of protein adduction induced by styrene and the
      halogenated styrenes were consistent with that of their cytotoxicities. The wild
      type cells were less susceptible to the toxicity of the corresponding model
      compounds than CYP2E1 cells. The present study provided insight into the roles of
      the biochemical and chemical properties of styrene in its cytotoxicity.

PMID- 22366344
TI  - Seroprevalence of Toxoplasma gondii in equids from Southern Spain.
AB  - Antibodies to Toxoplasma gondii were determined in serum samples from 616 equids
      (454 horses, 80 mules and 82 donkeys) in a cross-sectional study of 420 herds in
      Andalusia (Southern Spain), the region with the highest number of equids in
      Spain. Antibodies to T. gondii were found in 10.8% horses, 15.0% mules and 25.6%
      donkeys by using the modified agglutination test (MAT) at a cut-off of 1:25. Herd
      seroprevalence for horses, mules and donkeys was 14.7% (48/327), 23.9% (11/46)
      and 34.0% (16/47), respectively, and 75 herds (17.8%) had at least one
      seropositive animal. Significant differences in T. gondii seroprevalence were
      observed among species, with donkeys having the highest seroprevalence and horses
      the lowest (P=0.04). Seroprevalence was significantly higher in herds with
      presence of domestic ruminants. This study is the first report of the presence of
      T. gondii antibodies in equine species in Spain and the first reporting T. gondii
      infection in donkeys in Europe. The presence of antibodies is indication of
      contact with the parasite and therefore, consumption of equine meat could be a
      potential source of human infection in Spain.

PMID- 22366345
TI  - Increased frequency and enhanced perception of reflux in non-erosive reflux
      disease patients non-responders to proton pump inhibitors.
AB  - BACKGROUND: The unsatisfactory response to medical treatment in non-erosive
      patients is becoming a real challenge for gastroenterologists. Non-responder
      patients, evaluated under treatment, present symptoms which are related to non
      acidic, mixed and proximal reflux episodes. METHODS: To elucidate the reflux
      pattern and mechanisms related to persistence of symptoms despite treatment,
      oesophageal pH-impedance was performed in 55 non-erosive responder and 24 non
      responder patients, studied off therapy. Ten responder and 10 non-responder
      patients underwent a repeated study during proton pump inhibitor treatment.
      RESULTS: Non-responders were characterised by a higher overall number and larger
      proportion of symptomatic reflux episodes. Non-responders were also characterised
      by an enhanced sensitivity to acidic, mixed and proximal refluxes. Weakly acidic
      reflux accounted for 29% of symptomatic refluxes in non-responders and 34% in
      responders. Proportions of acidic and weakly acidic reflux episodes were
      comparable both in responders and non-responders when analysed off and on
      treatment. CONCLUSIONS: An increased overall number of reflux episodes and
      enhanced sensitivity to reflux are strongly associated with treatment failure.
      Treatment strategies aimed at decreasing transient lower oesophageal sphincter
      relaxations, pain modulators or anti-reflux surgery should be considered in non
      responders in whom a significant relationship between symptoms and reflux has
      been confirmed.

PMID- 22366346
TI  - Integration of an atmospheric dispersion model with a dynamic multimedia fate
      model: development and illustration.
AB  - Growing attention is devoted to understand the influence of the short-term
      variations in air concentrations on the environmental fate of semivolatile
      organic compounds (SVOCs) such as polycyclic aromatic hydrocarbons (PAHs). These
      variations are ascribable to factors such as temperature-mediated air-surface
      exchange and variability of planetary boundary layer (PBL) height and structure.
      But when investigating the fate of SVOCs at a local scale, further variability
      can derive from specific point source contributions. In this context, a new
      modeling approach (AirPlus) which integrates a previously developed model
      (AirFug) with an air dispersion model (AERMOD) is presented. The integrated model
      is illustrated for two PAHs in a Northern Italy scenario. Results show how
      chemical contributions deriving from background advective inflows, local
      emissions and a point source interact in an hourly-varying meteorological
      scenario to determine air concentration rapid changes and the consequent response
      of the soil compartment.

PMID- 22366347
TI  - Concentration responses to organochlorines in Phragmites australis.
AB  - Phragmites australis shows potential for the phytoremediation of chlorinated
      chemicals. Also there has been some attempt to determine the phytotoxic effects
      of organochlorines (OC). This study reports for lindane (HCH), monochlorobenzene
      (MCB), 1,4-dichlorobenzene (DCB) and 1,2,4-trichlorobenzene (TCB), a no-observed
      effect-concentration (NOEC(7d)) that was 1000-300,000 times higher than
      environmental concentrations. Nevertheless, the combined OC mixture (NOEC(7d)
      level of each congener) induced a synergistic toxic effect, causing a severe drop
      (70%) in chlorophyll concentration. The mixture 0.2 mg L(-1) MCB+0.2 mg L(-1)
      DCB+2.5 mg L(-1) TCB+0.175 mg L(-1) HCH, that was 15 times more concentrated than
      environmental OC mixture, did not cause phytotoxicity during 21 days. Antioxidant
      enzymes were affected immediately after the start of exposure (3 days), but the
      plants showed no signs of stress thereafter. These data suggest that
      environmental OC mixtures do not pose a significant risk to P. australis.

PMID- 22366348
TI  - Effects of aging on the digestive solubilization of Cu from sediments.
AB  - Solubilization of particulate Cu by different solutions, mimicking digestive
      fluids of deposit-feeders, was quantified in stable isotope (65)Cu-spiked
      sediments (with 3 days-2 months Cu-sediment contact time or aging). Copper
      solubilization generally decreased with prolonged aging. However, such decrease
      became less evident after 1 month and equilibrium of Cu in sediments could be
      reached after 2 months. Aging effects on Cu solubilization can be explained by
      the changes in Cu geochemical fractionation with aging: Cu generally transferred
      from more mobile phases (carbonate and Fe-Mn associated) to more refractory
      phases (organic associated and residual phase). Besides Cu geochemical
      fractionation, digestive fluid composition and different Cu solubilization
      pathways involved, as well as sedimentary organic content, could all affect the
      digestive solubilization of Cu and its change with aging. Our results emphasize
      the necessity of considering Cu aging in laboratory sediment toxicity
      experiments, and in risk assessment of Cu contaminated sediments.

PMID- 22366349
TI  - Metal leaching along soil profiles after the EDDS application--a field study.
AB  - One concern about the chelant-enhanced phytoextraction is the potential metal
      leaching associated with chelant application. A field study was carried out and
      the metal leaching along the 60-cm depth soil profiles were evaluated within 36
      days after the biodegradable chelant EDDS was applied. Results showed EDDS
      significantly increased soluble Cu in the top 5 cm soil layer 1 day after the
      application, and the increase of soluble metals was generally limited in the top
      20 cm soil. Metal speciation analysis indicated all Cu and Zn were in forms of Cu
      EDDS and Zn-EDDS complexes in soil solution, and Ca was the major competitor with
      trace metals to EDDS. The soluble metals decreased quickly with time, and no
      significant difference was observed in the extractable Cu between EDDS treatments
      and the controls 22 days after the EDDS addition. The potential leaching
      associated with biodegradable EDDS addition may be controlled under field
      conditions.

PMID- 22366350
TI  - A humanized IgG but not IgM antibody is effective in prophylaxis and therapy of
      yellow fever infection in an AG129/17D-204 peripheral challenge mouse model.
AB  - Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne
      virus found in tropical regions of Africa and South America that causes severe
      hepatic disease and death in humans. Despite the availability of effective
      vaccines, YFV is responsible for an estimated 200,000 cases and 30,000 deaths
      annually. There are currently no prophylactic or therapeutic strategies approved
      for use in human YFV infections. Furthermore, implementation of YFV 17D-204
      vaccination campaigns has become problematic due to an increase in reported post
      vaccinal adverse events. We have created human/murine chimeric MAbs of a YFV
      reactive murine monoclonal antibody (mMAb), 2C9, that was previously shown to
      protect mice from lethal YFV infection and to have therapeutic activity. The new
      chimeric (cMAbs) were constructed by fusion of the m2C9 IgG gene variable regions
      with the constant regions of human IgG and IgM and expressed in Sp2 murine
      myelomas. The 2C9 cMAbs (2C9-cIgG and 2C9-cIgM) reacted with 17D-204 vaccine
      strain in an enzyme-linked immunosorbent assay and neutralized virus in vitro
      similarly to the parent m2C9. Both m2C9 and 2C9-cIgG when administered
      prophylactically 24h prior to infection protected AG129 mice from peripheral 17D
      204 challenge at antibody concentrations >=1.27 MUg/mouse; however, the 2C9-cIgM
      did not protect even at a dose of 127 MUg/mouse. The 17D-204 infection of AG129
      mice is otherwise uniformly lethal. While the m2C9 was shown previously to be
      therapeutically effective in YFV-infected BALB/c mice at day 4 post-infection,
      the m2C9 and 2C9-cIgG demonstrated therapeutic activity only when administered 1
      day post-infection in 17D-204-infected AG129 mice.

PMID- 22366351
TI  - Coronary perfusion pressure during external chest compression in pseudo-EMD,
      comparison of systolic versus diastolic synchronization.
AB  - BACKGROUND: The fraction of cardiac arrest patients presenting with pulseless
      electrical activity is increasing, and it is likely that many of these patients
      have pseudo-electromechanical dissociation (P-EMD), a state in which there is
      residual cardiac contraction without a palpable pulse. The efficacy of
      cardiopulmonary resuscitation (CPR) with external chest compression synchronized
      with the P-EMD cardiac systole and diastole has not been fully evaluated.
      HYPOTHESIS: During external chest compression in P-EMD, the coronary perfusion
      pressure (CPP) will be greater with systolic synchronization compared with
      diastolic phase synchronization. METHODS: A porcine model of P-EMD induced by
      progressive hypoxia with peak aortic pressures targeted to 50 mmHg was used. CPR
      chest compressions were performed by either load distributing band or vest
      devices. Paired 10s intervals of systolic and diastolic synchronization were
      performed randomly during P-EMD, and aortic, right atrial and CPP were compared.
      RESULTS: Stable P-EMD was achieved in 8 animals, with 2.6+/-0.5 matched
      synchronization pairs per animal. Systolic synchronization was association with
      increases in relaxation phase aortic pressure (41.7+/-8.9 mmHg vs. 36.9+/-8.2
      mmHg), and coronary perfusion pressure (37.6+/-11.7 mmHg vs. 30.2+/-9.6 mmHg).
      Diastolic synchronization was associated with an increased right atrial pressure
      (6.7+/-4.1 mmHg vs. 4.1+/-5.7 mmHg). CONCLUSION: During P-EMD, synchronization of
      external chest compression with residual cardiac systole was associated with
      higher CPP compared to synchronization with diastole.

PMID- 22366352
TI  - The frequency and timing of epileptiform activity on continuous
      electroencephalogram in comatose post-cardiac arrest syndrome patients treated
      with therapeutic hypothermia.
AB  - AIM: The incidence and timing of electrographic seizures and epileptiform
      activity in comatose, adult, post-cardiac arrest syndrome (PCAS) patients treated
      with therapeutic hypothermia (TH) have not been extensively investigated. We
      hypothesized that onset most frequently occurs within the first 24 h post-arrest
      and is associated with poor neurologic outcome. METHODS: Single-center,
      retrospective analysis of a cohort of 38 comatose PCAS patients treated with TH
      and continuous-EEG-monitoring (cEEG), initiated as soon as possible after ICU
      admission. All raw cEEG waveform records were cleared of annotations and clinical
      information and classified by two fellowship-trained electroencephalographers.
      RESULTS: Twenty-three percent (9/38) of patients had electrographic seizures
      (median onset 19 h post-arrest); 5/9 (56%) had seizure-onset prior to rewarming;
      7/9 (78%) had status epilepticus. Forty-five percent (17/38) had evidence of
      epileptiform activity (electrographic seizures or interictal epileptiform
      discharges), typically occurring during first 24 h post-arrest. Interictal
      epileptiform activity was highly associated with later detection of
      electrographic seizures (6/14, 43%, p=0.001). Ninety-four percent (16/17) of
      patients with epileptiform activity had poor neurologic outcome or death at
      discharge (Cerebral Performance Category scale 3-5; p=0.002) as did all (9/9)
      patients with electrographic seizures (p=0.034). CONCLUSIONS: Electrographic
      seizures and epileptiform activity are common cEEG findings in comatose, PCAS
      patients treated with TH. In this preliminary study, most seizures were status
      epilepticus, had onset prior to rewarming, evolved from prior interictal
      epileptiform activity, and were associated with short-term mortality and poor
      neurologic outcome. Larger, prospective studies are needed to further
      characterize seizure activity in comatose post-arrest patients.

PMID- 22366353
TI  - The continuous quality improvement project for telephone-assisted instruction of
      cardiopulmonary resuscitation increased the incidence of bystander CPR and
      improved the outcomes of out-of-hospital cardiac arrests.
AB  - REVIEW: In 2007, the Ishikawa Medical Control Council initiated the continuous
      quality improvement (CQI) project for telephone-assisted cardiopulmonary
      resuscitation (telephone-CPR), which included instruction on chest-compression
      only CPR, education on how to recognise out-of-hospital cardiac arrests (OHCAs)
      with agonal breathing, emesis and convulsion, recommendations for on-line or
      redialling instructions and feedback from emergency physicians. This study aimed
      to investigate the effect of this project on the incidence of bystander CPR and
      the outcomes of OHCAs. MATERIALS AND METHODS: The baseline data were
      prospectively collected on 4995 resuscitation-attempted OHCAs, which were
      recognised or witnessed by citizens rather than emergency medical technicians
      during the period of February 2004 to March 2010. The incidence of telephone-CPR
      and bystander CPR, as well as the outcomes of the OHCAs, was compared before and
      after the project. RESULTS: The incidence of telephone-CPR and bystander CPR
      significantly increased after the project (from 42% to 62% and from 41% to 56%,
      respectively). The incidence of failed telephone-CPR due to human factors
      significantly decreased from 30% to 16%. The outcomes of OHCAs significantly
      improved after the projects. A multiple logistic regression analysis revealed
      that the CQI project is one of the independent factors associated with one-year
      (1-Y) survival with favourable neurological outcomes (odds ratio=1.81, 95%
      confidence interval=1.20-2.76). CONCLUSIONS: The CQI project for telephone-CPR
      increased the incidence of bystander CPR and improved the outcome of OHCAs. A CQI
      project appeared to be essential to augment the effects of telephone-CPR.

PMID- 22366354
TI  - A hybrid symbolic-numerical method for determining model structure.
AB  - In this article, we present a method for determining whether a model is at least
      locally identifiable and in the case of non-identifiable models whether any of
      the parameters are individually at least locally identifiable. This method
      combines symbolic and numeric methods to create an algorithm that is extremely
      accurate compared to other numeric methods and computationally inexpensive. A
      series of generic computational steps are developed to create a method that is
      ideal for practitioners to use. The algorithm is compared to symbolic methods for
      two capture-recapture models and a compartment model.

PMID- 22366355
TI  - Sudden asphyxia caused by retropharyngeal hematoma after blunt thyrocervical
      artery injury.
AB  - BACKGROUND: Retropharyngeal hematomas are often associated with blunt cervical
      spine injury. Generally, they improve with conservative treatment; however,
      rarely, airway obstruction occurs due to delayed swelling of retropharyngeal
      hematoma. OBJECTIVES: To report a case of sudden asphyxia due to retropharyngeal
      hematoma caused by blunt thyrocervical artery injury. CASE REPORT: A 30-year-old
      woman was admitted to the Emergency Department of Tokai University Hospital 4h
      after injury in a motor vehicle collision. On arrival, she had severe dyspnea and
      neck swelling; thereafter, a 26-mm-thick retropharyngeal swelling was visualized
      on lateral cervical plain X-ray study, extending from C1 anterior vertebrae to
      mediastinum. Emergency intubation was performed for the asphyxia. Because
      extravasation of contrast agent was observed in the hematoma on emergency
      contrast-enhanced computed tomography (CT) scan, emergency angiography was
      performed, from which we diagnosed a hemorrhage from the right thyrocervical
      artery. CONCLUSION: If a patient with a non-displaced cervical spine injury
      suffers airway obstruction due to retropharyngeal hematoma, vigorous hemorrhage
      from a thyrocervical artery injury should be considered as the cause, and
      emergency contrast-enhanced CT scan of the neck should be performed after
      emergent tracheal intubation.

PMID- 22366356
TI  - RNA editing of the Q/R site of GluA2 in different cultured cell lines that
      constitutively express different levels of RNA editing enzyme ADAR2.
AB  - Adenosine deaminase acting on RNA 2 (ADAR2) catalyzes RNA editing at the
      glutamine/arginine (Q/R) site of GluA2, and an ADAR2 deficiency may play a role
      in the death of motor neurons in ALS patients. The expression level of ADAR2 mRNA
      is a determinant of the editing activity at the GluA2 Q/R site in human brain but
      not in cultured cells. Therefore, we investigated the extent of Q/R site-editing
      in the GluA2 mRNA and pre-mRNA as well as the ADAR2 mRNA and GluA2 mRNA and pre
      mRNA levels in various cultured cell lines. The extent of the GluA2 mRNA editing
      was 100% except in SH-SY5Y cells, which have a much lower level of ADAR2 than the
      other cell lines examined. The ADAR2 activity at the GluA2 pre-mRNA Q/R site
      correlated with the ADAR2 mRNA level relative to the GluA2 pre-mRNA. SH-SY5Y
      cells expressed higher level of the GluA2 mRNA in the cytoplasm compared with
      other cell lines. These results suggest that the ADAR2 expression level reflects
      editing activity at the GluA2 Q/R site and that although the edited GluA2 pre
      mRNA is readily spliced, the unedited GluA2 pre-mRNA is also spliced and
      transported to the cytoplasm when ADAR2 expression is low.

PMID- 22366357
TI  - Costs of abandoned coal mine reclamation and associated recreation benefits in
      Ohio.
AB  - Two hundred years of coal mining in Ohio have degraded land and water resources,
      imposing social costs on its citizens. An interdisciplinary approach employing
      hydrology, geographic information systems, and a recreation visitation function
      model, is used to estimate the damages from upstream coal mining to lakes in
      Ohio. The estimated recreational damages to five of the coal-mining-impacted
      lakes, using dissolved sulfate as coal-mining-impact indicator, amount to $21
      Million per year. Post-reclamation recreational benefits from reducing sulfate
      concentrations by 6.5% and 15% in the five impacted lakes were estimated to range
      from $1.89 to $4.92 Million per year, with a net present value ranging from
      $14.56 Million to $37.79 Million. A benefit costs analysis (BCA) of recreational
      benefits and coal mine reclamation costs provides some evidence for potential
      Pareto improvement by investing limited resources in reclamation projects.

PMID- 22366358
TI  - Carbonised red mud--a new water treatment product made from a waste material.
AB  - Proposals to use red mud, the waste produced by the extraction of alumina from
      bauxite ore in the Bayer process, as a material for treatment of heavy metal
      contaminated water are limited by its inherent alkalinity and variability.
      Attempts to lower its pH have been largely unreliable. However, an alternative
      strategy is carbonisation of red mud by catalytic hydrocarbon cracking, which
      results in a magnetic material of greater surface area. The efficacy of this
      material has been compared with that of the untreated parent red mud and
      acidified red mud for the sorption of CrO(4)(2-), Cu(2+) and Pb(2+). Carbonised
      red mud does not remove CrO(4)(2-) from solution, but shows enhancement of Cu(2+)
      and Pb(2+) removal. There is an approximate ten-fold increase in removal of
      Cu(2+) and Pb(2+) by carbonised red mud compared with acidified red mud.

PMID- 22366359
TI  - The economic benefits of rainwater-runoff reduction by urban green spaces: a case
      study in Beijing, China.
AB  - Urbanization involves the replacement of vegetated surfaces with impervious built
      surfaces, and it often results in an increase in the rate and volume of rainwater
      surface runoff. Urban green spaces play a positive role in rainwater-runoff
      reduction. However, few studies have explored the benefits of rainwater-runoff
      reduction by urban green spaces. Based on inventory data of urban green spaces in
      Beijing, the paper evaluated the economic benefits of rainwater-runoff reduction
      by urban green spaces, using the rainwater-runoff-coefficient method as well as
      the economic valuation methods. The results showed that, 2494 cubic meters of
      potential runoff was reduced per hectare of green area and a total volume of 154
      million cubic meters rainwater was stored in these urban green spaces, which
      almost corresponds to the annual water needs of the urban ecological landscape in
      Beijing. The total economic benefit was 1.34 billion RMB in 2009 (RMB: Chinese
      currency, US$1=RMB6.83), which is equivalent to three-quarters of the maintenance
      cost of Beijing's green spaces; the value of rainwater-runoff reduction was 21.77
      thousand RMB per hectare. In addition, the benefits in different districts and
      counties were ranked in the same order as urban green areas, and the average
      benefits per hectare of green space showed different trends, which may be related
      to the impervious surface index in different regions. This research will
      contribute to an understanding of the role that Beijing's green spaces play in
      rainwater regulation and in the creation and scientific management of urban green
      spaces.

PMID- 22366360
TI  - A spatio-temporal analysis of fire recurrence and extent for semi-arid savanna
      ecosystems in Southern Africa using moderate-resolution satellite imagery.
AB  - Savanna ecosystems are semi-arid and fire-prone. Increasing temperatures and
      decreasing precipitation in Southern Africa will probably have a series of strong
      impacts on the various components of fire regimes in these ecosystems that will,
      in turn, affect their ecology, structure, and function. This paper presents a
      geospatial analysis to quantify changes in fire frequency, seasonality and
      spatial distribution during the last decade and creates a fire return interval
      map for the core area of the Kavango-Zambezi Transfrontier Conservation Area,
      which spans five Southern African countries and is the largest cooperative
      multistate conservation region in the world. To disentangle the relative
      contribution of environmental variability from country-specific land management
      decisions in driving changes in fire regimes, we use two different products from
      the MODIS Terra platform (Active Fire and Burned Area products), TRMM
      precipitation data and the Multivariate ENSO Index data to analyze change in fire
      regimes among the five countries, differentiating between different land uses
      such as protected areas, forest reserves, and communal lands and accounting for
      specific changes in fire management policies. There are significant differences
      in fire frequencies between countries with more effective fire management
      (Botswana and Zimbabwe) and countries where anthropogenic, mainly early-dry
      season, burning is largely uncontrolled (Namibia, Angola, and Zambia), both
      within and outside protected areas, while all countries and land-use units show
      an overall increasing trend in fire occurrences. Large fire occurrences increased
      up to 200% in the period before the beginning of the natural fire season in
      Namibia, where a new prescribed burn policy was introduced in 2006, while the
      other countries show a slightly different shift in seasonality of increasing fire
      occurrences mainly during the dry season. The mean size of fires also increases
      significantly across all land uses despite increasing fire prevention efforts in
      most protected areas in the five countries. These findings can contribute to more
      effective transboundary natural resource and wildlife habitat management by
      providing a baseline assessment of fire return intervals across five countries
      with different fire management policies and have implications in the climate
      change arena.

PMID- 22366361
TI  - A multi-scale modelling approach for analysing landscape service dynamics.
AB  - Shifting societal needs drive and shape landscapes and the provision of their
      services. This paper presents a modelling approach to visualize the regional
      spatial and temporal dynamics in landscape service supply as a function of
      changing landscapes and societal demand. This changing demand can result from
      different policy targets. In this paper we conceptualise the system in which
      these dynamics take place by explicitly addressing (i) the multifunctional
      character of a landscape, (ii) the different spatial levels at which interactions
      between landscape service supply, demand, and land management occur, and (iii)
      trade-offs in service supply as a result of land management actions. Next, we
      translate the resulting conceptual framework into an operational model. As a
      demonstration, this model is applied to simulate changes in landscape service
      supply driven by regional policies in a rural region of the Netherlands. This
      application demonstrates potential trade-offs, which emerge in a spatially
      explicit way in the region over time. It illustrates the potential relevance of
      modelling landscape service dynamics for environmental management and decision
      making.

PMID- 22366362
TI  - Isolation and identification of Acanthamoeba species from thermal spring
      environments in southern Taiwan.
AB  - Acanthamoeba species are free-living amoebae found in a range of environments.
      Within this genus, a number of species are recognized as human pathogens,
      potentially causing Acanthamoeba keratitis, granulomatous amoebic encephalitis,
      and chronic granulomatous lesions. In this study, 60 water samples were taken
      from four thermal spring recreation areas in southern Taiwan. We detected living
      Acanthamoeba spp. based on culture-confirmed detection combined with the
      molecular taxonomic identification method. Living Acanthamoeba spp. were detected
      in nine (15%) samples. The presence or absence of Acanthamoeba spp. in the water
      samples depended significantly on the pH value. The most frequently identified
      living Acanthamoeba genotype was T15 followed by T4, Acanthamoeba spp., and T2.
      Genotypes T2, T4, and T15 of Acanthamoeba, are responsible for Acanthamoeba
      keratitis as well as granulomatous amoebic encephalitis, and should therefore be
      considered a potential health risk associated with human activities in thermal
      spring environments.

PMID- 22366363
TI  - Strongyloides papillosus: changes in transcript levels of lysozyme and aspartic
      protease 2 in percutaneously migrated larvae.
AB  - The infection of the host is the crucial event in the life-cycle of parasites. To
      understand the molecular mechanisms of this important step, different methods are
      used in present studies. For analysis of changes in transcript levels the most
      sensitive method is the quantitative real-time PCR (qPCR). For an accurate
      analysis the evaluation of a set of adequate reference genes is necessary. The
      present study aimed to analyse the transcriptional levels of two genes of
      interest, the putative aspartic protease Spa-asp-2 and the putative lysozyme Spa
      lys, in infective, free-living larvae of Strongyloides papillosus at different
      ages and from long-term and short-term infections and percutaneously migrated
      ("parasitic") larvae. Percutaneously migrated larvae were collected using the
      PERL chamber system and ovine skin in vitro. Reference genes identified as most
      suitable for transcriptional analysis according to geNorm analysis were genes for
      the eukaryotic translation elongation factor 1 alpha (Spa-eft-2), actin variation
      2 (Spa-act-v2) and beta tubulin (Spa-tbb-1). Transcriptional analysis of the
      genes in percutaneously migrated larvae showed an upregulation of Spa-asp-2,
      while Spa-lys was downregulated. Data from the presented study provide a first
      glance into the changes of transcript levels of S. papillosus induced by
      percutaneous migration.

PMID- 22366364
TI  - Intra-articular osteoid osteoma in the proximal ulna combined with radial head
      subluxation: a case report.

PMID- 22366365
TI  - Does hyaluronate injection work in shoulder disease in early stage? A
      multicenter, randomized, single blind and open comparative clinical study.
AB  - BACKGROUND: This study assessed the hypothesis that injection of high-molecular
      weight hyaluronate in the treatment of subacromial impingement syndrome is
      effective and safe, compared with corticosteroid injection in the shoulder joint.
      METHODS: One hundred five patients were allocated randomly into 2 groups: 1 group
      was injected once a week for 3 weeks with hyaluronate and the other group was
      injected once with corticosteroid. All injections were guided to the subacromial
      space by an ultrasonogram. Eighty patients were followed up for 12 weeks after
      the injection: 38 patients in the hyaluronate group and 42 patients in the
      corticosteroid group. The functional outcome was measured using the American
      Shoulder and Elbow Surgeons standardized shoulder assessment form (ASES).
      RESULTS: The Visual Analogue Scale (VAS) score at 12 weeks was decreased
      significantly from 58.6 +/- 19.3 to 24.6 +/- 23.1 in the hyaluronate group (P <
      .0001) and from 57.2 +/- 19.9 to 36.9 +/- 26.5 (P < .0001) in the corticosteroid
      group. There was a significant difference in the VAS score between the hyaluronic
      acid group and corticoid group (P = .0180) at 12 weeks. The functional ASES
      scores in the hyaluronate and corticosteroid groups were increased from 17.6 +/-
      4.8 to 22.4 +/- 6.5 and from 17.3 +/- 4.9 to 21.7 +/- 5.8, respectively, at 12
      weeks (P = .4825). There was no difference in the number of patients requiring
      rescue medication between the hyaluronate group and corticosteroid group at 12
      weeks (P = .9254). CONCLUSION: A subacromial hyaluronate injection to treat
      impingement syndrome produces similar pain and functional improvement to
      corticosteroid at a short-term follow-up.

PMID- 22366366
TI  - The pharmacogenomics of clopidogrel.

PMID- 22366367
TI  - The "cookbook" approach to generating cell type of interest: anterior pituitary
      cells from embryonic stem cells.

PMID- 22366368
TI  - ITS2 database IV: interactive taxon sampling for internal transcribed spacer 2
      based phylogenies.
AB  - The first step of any molecular phylogenetic analysis is the selection of the
      species and sequences to be included, the taxon sampling. Already here different
      pitfalls exist. Sequences can contain errors, annotations in databases can be
      inaccurate and even the taxonomic classification of a species can be wrong.
      Usually, these artefacts become evident only after calculation of the
      phylogenetic tree. Following, the taxon sampling has to be corrected iteratively.
      This can become tedious and time consuming, as in most cases the taxon sampling
      is de-coupled from the further steps of the phylogenetic analysis. Here, we
      present the ITS2 Workbench (http://its2.bioapps.biozentrum.uni-wuerzburg.de/),
      which eliminates this problem by a tight integration of taxon sampling, secondary
      structure prediction, multiple alignment and phylogenetic tree calculation. The
      ITS2 Workbench has access to more than 280,000 ITS2 sequences and their
      structures provided by the ITS2 database enabling sequence-structure based
      alignment and tree reconstruction. This allows the interactive improvement of the
      taxon sampling throughout the whole phylogenetic tree reconstruction process.
      Thus, the ITS2 Workbench enables a fast, interactive and iterative taxon sampling
      leading to more accurate ITS2 based phylogenies.

PMID- 22366369
TI  - Diversification rates and chromosome evolution in the most diverse angiosperm
      genus of the temperate zone (Carex, Cyperaceae).
AB  - The sedge family (Cyperaceae: Poales; ca. 5600 spp.) is a hyperdiverse
      cosmopolitan group with centres of species diversity in Africa, Australia,
      eastern Asia, North America, and the Neotropics. Carex, with ca. 40% of the
      species in the family, is one of the most species-rich angiosperm genera and the
      most diverse in temperate regions of the Northern Hemisphere, making it atypical
      among plants in that it inverts the latitudinal gradient of species richness.
      Moreover, Carex exhibits high rates of chromosome rearrangement via fission,
      fusion, and translocation, which distinguishes it from the rest of the
      Cyperaceae. Here, we use a phylogenetic framework to examine how the onset of
      contemporary temperate climates and the processes of chromosome evolution have
      influenced the diversification dynamics of Carex. We provide estimates of
      diversification rates and map chromosome transitions across the evolutionary
      history of the main four clades of Carex. We demonstrate that Carex underwent a
      shift in diversification rates sometime between the Late Eocene and the
      Oligocene, during a global cooling period, which fits with a transition in
      diploid chromosome number. We suggest that adaptive radiation to novel temperate
      climates, aided by a shift in the mode of chromosome evolution, may explain the
      large-scale radiation of Carex and its latitudinal pattern of species richness.

PMID- 22366370
TI  - Three novel BRCA1/BRCA2 mutations in breast/ovarian cancer families in Croatia.
AB  - BRCA1 and BRCA2 genes from 167 candidates (145 families) were scanned for
      mutations. We identified 14 pathogenic point mutations in 17 candidates, 9 in
      BRCA1 and 5 in BRCA2. Of those, 11 have been previously described and 3 were
      novel (c.5335C>T in BRCA1 and c.4139_4140dupTT and c.8175G>A in BRCA2). No large
      deletions or duplications involving BRCA1 and BRCA2 genes were identified. No
      founder mutations were detected for the Croatian population. Croatia shares most
      of the mutations with neighboring Slovenia and also with Germany, Austria and
      Poland. Two common sequence variants in BRCA1, c.2077G>A and c.4956G>A, were
      found more frequently in mutation carriers compared to healthy controls. No
      difference in BRCA2 variants was detected between the groups. Haplotype inference
      showed no difference in haplotype distributions between deleterious mutation
      carriers and non-carriers in neither BRCA1 nor BRCA2. In silico analyses
      identified one BRCA1 sequence variant (c.4039A>G) and two BRCA2 variants
      (c.5986G>A and c.6884G>C) as harmful with high probability, and inconclusive
      results were obtained for our novel BRCA2 variant c.3864_3866delTAA. Combination
      of QMPSF and HRMA methods provides high detection rate and complete coverage of
      BRCA1/2 genes. Benefit of BRCA1/2 mutation testing is clear, since we detected
      mutations in young unaffected women, who will be closely monitored for breast and
      ovarian cancer.

PMID- 22366371
TI  - Aberrant expression of FcgammaRIIIA (CD16) contributes to the development of
      atherosclerosis.
AB  - Previous studies have documented that Fc receptor III A of immunoglobulin G
      (FcgammaRIIIA, also named CD16) is involved in the development of coronary heart
      disease (CHD). However, the mechanism responsible for FcgammaRIIIA's in
      contribution to CHD development remains largely unclear. Herein, we investigated
      the possible role of FcgammaRIIIA in the development of atherosclerosis. Our
      results showed that the elevated level of FcgammaRIIIA on monocytes closely
      correlated to the adhesive efficiency of human umbilical vein endothelial cells
      (HUVECs) in vitro. Importantly, we also observed increased population of CD16(+)
      monocytes and elevated CD16 level on monocytes in ApoE(-/-) mice with
      characterized atherosclerosis after feeding with high-fat diet for 10weeks. The
      enhancement of CD16 on monocytes closely correlated to increased content of MMP-9
      in aorta and increased inflammatory cytokines in sera. In addition, similar to
      simvastatin, recombinant human M-CSF represented a robust inhibitory influence on
      plaque instability and inflammation. Taken together, these data established that
      FcgammaRIIIA (CD16)-mediated signaling orchestrated by interaction between
      monocytes and HUVECs, coupled with inflammatory cytokine stimulation and MMP
      activation, as a fundamental pathway linked to the development of atherosclerotic
      formation. Inhibition of FcgammaRIIIA or its signaling thus might represent a
      promising approach for the prevention and treatment of CHD.

PMID- 22366372
TI  - Characterization of metalloproteinases, oxidative status and inflammation levels
      in the different stages of fibrosis in HCV patients.
AB  - OBJECTIVES: This study was aimed at searching noninvasive markers of the
      transition from mild to severe fibrosis stage in HCV patients undergoing hepatic
      fibrosis. DESIGN AND METHODS: Thirty-three patients affected by chronic HCV vs.
      twenty healthy donors were evaluated for the serum levels of several circulating
      matrix metalloproteinases (MMPs), TRAIL and beta-NGF by multiplex biometric ELISA
      based immunoassay and anti- and pro-oxidant status (d-ROMs, BAP and NO) using a
      Diacron automated method. RESULTS: HCV patients displayed increased expression
      levels of MMP-8, MMP-9, TRAIL and beta-NGF, and an imbalance between pro- and
      antioxidant status, that contribute to liver fibrosis. CONCLUSIONS: Since the
      determination of these parameters represents a reliable and easily applicable
      method, these parameters are suggested as serum surrogate markers for HCV
      patients in the routine clinical practice.

PMID- 22366373
TI  - HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein
      activity in patients at risk for type 2 diabetes.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MS) and type 2 diabetes are highly
      associated with an abnormal lipoprotein profile, which may be generated and
      accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the
      difficulty in measuring CETP activity, the aim was to identify simple biochemical
      predictors of high CETP activity. DESIGN AND METHODS: Eighty five subjects at
      risk for type 2 diabetes were classified according to the presence of MS.
      Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated.
      RESULTS: As expected, MS patients presented higher concentration of glucose,
      insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS
      patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for
      MS, high CETP activity was defined as >250%ml-1 h-1. The predictive variables of
      high CETP were non-HDL-C>=160mg/dl (OR=11.1;95%IC=3.3-38.2;p<0.001) and HOMA
      IR>2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). CONCLUSIONS: High non-HDL-C and insulin
      resistance were predictors for increased CETP activity which measurement is not
      accessible for clinical laboratories.

PMID- 22366374
TI  - HIF-1 versus HIF-2--is one more important than the other?
AB  - Hypoxia is a state where oxygen availability/delivery is below the level
      necessary to maintain physiological oxygen tension for a particular tissue. It is
      well-established that when tissue demand exceeds its oxygen supply, a cascade of
      intracellular events is activated, with the elevation of the expression of
      hypoxia-inducible factors (HIFs). As a consequence, the extensive transcriptional
      response regulating angiogenesis, glucose metabolism, cell growth, metastasis and
      others processes is induced. The discovery of differences between HIF isoforms
      has provided new insights into HIFs biology. Importantly, the opposite effects
      can be exerted by HIF-1 and HIF-2 on the regulation of angiogenic response.
      Although both isoforms may upregulate the expression of pro-angiogenic vascular
      endothelial growth factor (VEGF), HIF-1 diminished the expression of interleukin
      8 (IL-8) by inhibition of the Nrf2 transcription factor whereas HIF-2 augmented
      expression of IL-8 in an Nrf2-independent way but via upregulation of SP-1
      activity. Moreover, the opposite regulation of c-Myc transcription factor by both
      HIF isoforms may influence IL-8 regulation. Complexity of effects exerted by both
      HIF isoforms resulting from the cooperation with other transcription factors
      should be subjected to intensive investigation especially in the context of pro
      and anti-angiogenic therapies.

PMID- 22366375
TI  - Relevance of new drug discovery to reduce NF-kappaB activation in cardiovascular
      disease.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is a main regulator of
      the expression of several genes involved in the activation of inflammation, cell
      proliferation, cell immunity and apoptosis. Excess or inappropriate activation of
      NF-kappaB has been observed in human inflammatory diseases, including
      atherosclerosis. Because of the extensive involvement of NF-kappaB signaling in
      human diseases, efforts have been made in developing inhibitors of this pathway.
      Here we will provide an overview of the biology of NF-kappaB activation pathways.
      We will here especially focus on current knowledge of the role of the classical
      ("canonical") NF-kappaB activation pathway as a potential therapeutic target for
      anti-atherosclerotic therapies in clinical applications, and discuss classical
      and novel therapeutic strategies to reduce its prolonged activation.

PMID- 22366376
TI  - Electric impedance sensing in cell-substrates for rapid and selective
      multipotential differentiation capacity monitoring of human mesenchymal stem
      cells.
AB  - Biosensor systems which enable impedance measurements on adherent cell layers
      under label-free conditions are considered powerful tools for monitoring specific
      biological characteristics. A radio frequency identification-based sensor
      platform was adopted to characterize cultivation and differentiation of human
      bone marrow-derived multipotent stem cells (bmMSC) over periods of up to several
      days and weeks. Electric cell-substrate impedance sensing was achieved through
      fabrication of sensitive elements onto glass substrates which comprised two comb
      shaped interdigitated gold electrodes covering an area of 1.8 mm*2 mm. The
      sensing systems were placed into the wells of a 6-well tissue culture plate,
      stacked onto a reader unit and could thus be handled and operated under sterile
      conditions. Continuous measurements were carried out with a sinusoidal voltage of
      35 mV at a frequency of 10 kHz. After seeding of human bmMSC, this sensor was
      able to trace significant impedance changes contingent upon cell spreading and
      adhesion. The re-usable system was further proven suitable for live examination
      of cell-substrate attachment or continuous cell monitoring up to several weeks.
      Induction of either osteogenic or adipogenic differentiation could be validated
      in bmMSC cultures within a few days, in contrast to state-of-the-art protocols,
      which require several weeks of cultivation time. In the context of medical cell
      production in a GMP-compliant process, the here presented interdigitated electric
      microsensor technology allows the documentation of MSC quality in a fast,
      efficient and reliable fashion.

PMID- 22366377
TI  - A label-free, G-quadruplex DNAzyme-based fluorescent probe for signal-amplified
      DNA detection and turn-on assay of endonuclease.
AB  - A novel G-quadruplex DNAzyme molecular beacon (G-DNAzymeMB) strategy is developed
      for assays of target DNA and restriction endonuclease. The detection system
      consists of G-DNAzymeMB strand and a blocker DNA by using the fluorescence of
      2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) catalyzed by G-DNAzymeMB
      as a signal reporter. G-DNAzymeMB exhibits peroxidase activity in its free
      hairpin structure, and forms a catalytically inactive hybrid when hybridized with
      blocker DNA. Upon displacement of blocker DNA by target DNA or cleavage by
      restriction endonuclease, G-DNAzymeMB is released and two lateral portions of G
      DNAzymeMB form a G-quadruplex structure, resulting in the recovery of catalytic
      activity which acts as a cofactor to catalyze H(2)O(2)-mediated oxidation of
      H(2)DCFDA. For DNA detection system, exonuclease III (Exo III)-catalyzed
      amplification strategy is introduced to improve the sensitivity and target DNA
      could be detected as low as 0.1 pM. With respect to restriction endonuclease
      detection system, 0.1 U/mL EcoRI endonuclease could be detected and this method
      could be easily transported to other restriction endonuclease analysis by simply
      changing the recognition sequence. These results demonstrate that the proposed G
      DNAzymeMB strategy could be used as a label-free, simple, sensitive and cost
      effective approach in analysis of target DNA and restriction endonuclease.

PMID- 22366378
TI  - White blood cell count and risk of gastric cancer incidence in a general Japanese
      population: the Hisayama study.
AB  - The authors examined the association between white blood cell (WBC) count and the
      development of gastric cancer in a 19-year follow-up study of 2,558 Japanese
      subjects aged >=40 years (1988-2007). The subjects were stratified into 4 groups
      according to baseline WBC quartile (<=4.4, 4.5-5.2, 5.3-6.3, or >=6.4 * 10(3)
      cells/MUL). During follow-up, 128 subjects developed gastric cancer. The age- and
      sex-adjusted incidence of gastric cancer increased linearly with higher WBC
      level: 1.7, 2.6, 3.9, and 5.4 per 1,000 person-years, respectively, for the 4
      quartile groups (P for trend < 0.01). The risk of gastric cancer was 2.22-fold
      (95% confidence interval: 1.19, 4.14) higher in the highest WBC quartile group
      than in the lowest group after adjustment for confounding factors. With respect
      to Helicobacter pylori infection status, H. pylori-seropositive subjects in the
      highest WBC quartile group showed a significantly greater risk of gastric cancer
      than those in the lower 3 quartile groups, whereas such an association was not
      observed in H. pylori-seronegative subjects. There was no evidence of
      heterogeneity in the association (P for heterogeneity = 0.65). The study findings
      suggest that higher WBC levels are a risk factor for gastric cancer, especially
      in subjects with H. pylori infection.

PMID- 22366379
TI  - Association of repeated exposure to antibiotics with the development of pediatric
      Crohn's disease--a nationwide, register-based finnish case-control study.
AB  - To determine whether childhood exposure to antibiotics is associated with the
      risk of developing inflammatory bowel disease (IBD), the authors conducted a
      national, register-based study comprising all children born in 1994-2008 in
      Finland and diagnosed with IBD by October 2010. The authors identified 595
      children with IBD (233 with Crohn's disease and 362 with ulcerative colitis) and
      2,380 controls matched for age, gender, and place of residence. The risk of
      pediatric Crohn's disease increased with the number of antibiotic purchases from
      birth to the index date and persisted when the 6 months preceding the case's
      diagnosis were excluded (for 7-10 purchases vs. none, odds ratio = 3.48, 95%
      confidence interval: 1.57, 7.34; conditional logistic regression). The
      association between Crohn's disease and antibiotic use was stronger in boys than
      in girls (P = 0.01). Cephalosporins showed the strongest association with Crohn's
      disease (for 3 purchases vs. nonuse, odds ratio = 2.82, 95% confidence interval:
      1.65, 4.81). Antibiotic exposure was not associated with the development of
      pediatric ulcerative colitis. Repeated use of antibiotics may reflect shared
      susceptibility to childhood infections and pediatric Crohn's disease or
      alternatively may trigger disease development.

PMID- 22366380
TI  - [Current status and future expectations of immunotherapy with allergens in
      asthma].

PMID- 22366381
TI  - Characterization and evaluation of self-microemulsifying sustained-release pellet
      formulation of puerarin for oral delivery.
AB  - The present study aims to develop self-microemulsifying drug delivery systems
      (SMEDDS) in sustained-release pellets of puerarin to enhance the oral
      bioavailability of puerarin. The performances of puerarin-SMEDDS including oils,
      emulsifiers, and co-emulsifiers were evaluated. Pseudo-ternary phase diagrams
      shows that the optimized formulation consisted of castor oil as the oil phase,
      Cremophor EL as the emulsifier, and 1,2-propanediol as the co-emulsifier. SMEDDS
      sustained-release pellets were prepared via extrusion-spheronization. The
      particle size distributions of the formulations were determined using
      transmission electron microscopy and scanning electronic microscopy. The mean
      particle size was 50 +/- 8 nm. The pharmacokinetics and bioavailability of the
      puerarin-SMEDDS sustained-release pellets and puerarin tablets were evaluated and
      compared in beagle dogs. The absolute bioavailability of the puerarin-SMEDDS
      sustained-release pellets was enhanced by approximately 2.6-fold compared with
      that of the puerarin tablet. The relative bioavailability (F(rel)) of the SMEDDS
      pellets was 259.7% compared with the tablet group. The results demonstrated that
      the puerarin-SMEDDS sustained-release pellets had a sustained-release effect, and
      could remarkably improve the oral bioavailability of puerarin.

PMID- 22366382
TI  - Microstructural investigation to the controlled release kinetics of monolith
      osmotic pump tablets via synchrotron radiation X-ray microtomography.
AB  - Tomographic imaging techniques are attractive tools for the visualization of the
      internal structural characteristics of pharmaceutical solid dosage forms. In this
      paper, the internal structure of the tablet core for a monolith osmotic drug
      delivery system, felodipine sustained-release tablet, was visualized via
      synchrotron radiation X-ray computed microtomography during the drug release
      process. The surface areas and three dimensional parameters of the tablet core
      were calculated based on the three dimensional reconstruction of the images. At
      different stages of the drug release process, the surface morphology, the
      hydration, the swelling, and the structure changing of the tablet, were
      visualized from the two dimensional monochrome X-ray images. The three
      dimensional volumes of the remaining tablet core correlated well with the
      percentages of felodipine (R=0.9988). Also, the three dimensional surface area
      almost unchanged during the drug release process, which clearly demonstrated the
      intrinsic drug release mechanism of the osmotic drug delivery system. In
      conclusion, the synchrotron radiation X-ray computed microtomography, with rapid
      acquisition, high intensity and micro-scale spatial resolution, was found to be a
      useful tool for the quantitative elucidation of the intrinsic drug release
      kinetics and the three dimensional parameters such as surface areas of the
      remained core obtained by the synchrotron radiation. Thus, X-ray computed
      microtomography can be considered as a new and complimentary analytical tool to
      standard compendial pharmaceutical tests for quality control of osmotic drug
      delivery systems.

PMID- 22366383
TI  - Metal-associated amyloid-beta species in Alzheimer's disease.
AB  - Highly concentrated metals such as Cu, Zn, and Fe are found in amyloid-beta
      (Abeta) plaques within the brain of Alzheimer's disease (AD). In vitro and in
      vivo studies have suggested that metal binding to Abeta could facilitate Abeta
      aggregation and generate reactive oxygen species (ROS), which could contribute to
      the neuropathogenesis of AD. The connection between metal-Abeta
      interaction/reactivity and AD development, however, has not been clearly revealed
      owing to the complexity of the disease. In this review, metal-Abeta
      interaction/reactivity and its relation to neurotoxicity are briefly discussed.
      Additionally, our review illustrates the recent progress of small molecules,
      capable of targeting metal-Abeta species and modulating their
      interaction/reactivity, which could offer a promising approach to interrogate
      their role in AD.

PMID- 22366384
TI  - The hows and whys of aerobic H2 metabolism.
AB  - The bacterial [NiFe]-hydrogenases have been classified as either 'standard' or
      'O2-tolerant' based on their ability to function in the presence of O2.
      Typically, these enzymes contain four redox-active metal centers: a Ni-Fe-CO-2CN-
      active site and three electron-transferring Fe-S clusters. Recent research
      suggests that, rather than differences at the catalytic active site, it is a
      novel Fe-S cluster electron transfer (ET) relay that controls how [NiFe]
      hydrogenases recover from O2 attack. In light of recent structural data and
      mutagenic studies this article reviews the molecular mechanism of O2-tolerance in
      [NiFe]-hydrogenases and discusses the biosynthesis of the unique Fe-S relay.

PMID- 22366385
TI  - The potential of organometallic complexes in medicinal chemistry.
AB  - Organometallic complexes have unique physico-chemical properties, which have been
      widely used in homogenous catalysis, for example, for the synthesis of lead
      compounds and drug candidates. Over the past two decades, a few scientists from
      all over the world have extended the use of the specific characteristics of these
      compounds (e.g. structural diversity, possibility of ligand exchange, redox and
      catalytic properties) for medicinal purposes. The results are stunning. A few
      organometallic compounds have already entered clinical trials and it can be
      anticipated that several more will follow in coming years. In this short review,
      we present the specific advantages that organometallic metal complexes have over
      purely organic and also coordination compounds. Furthermore, using specific
      examples, we illustrate how these particular properties can be put to good use in
      medicinal chemistry. The examples we present have an emphasis on, but are not
      restricted to, anti-cancer activity.

PMID- 22366386
TI  - Does the prevention paradox apply to various alcohol habits and problems among
      Swedish adolescents?
AB  - BACKGROUND: The prevention paradox states that a majority of alcohol-related
      problems in a population come from moderate drinkers because they are more
      numerous than heavy drinkers, although the latter have a higher individual risk
      of adverse outcomes. We examined the extent to which the prevention paradox
      applies to the relationship between alcohol consumption, heavy episodic drinking
      (HED) and alcohol-related problems in adolescents; an area in which studies are
      lacking. METHODS: A total of 7288 alcohol-consuming adolescents aged 13-17 years
      were examined. The proportions (%) of problems related to drinking measures [the
      upper 10% and bottom 90% of drinkers by annual alcohol intake, and those with
      frequent (monthly), less frequent, and no heavy drinking episodes] were
      calculated. RESULTS: The bottom 90% of consumers by annual intake accounted for a
      large majority of the alcohol-related problems among boys and girls at all ages.
      The share of problems accounted for by monthly HEDs increased with age, from ~10%
      among those aged 13 years to >50% among those aged 17 years. Attributable
      proportions for the top 10% alcohol consumers ranged between 22% and 37%.
      CONCLUSIONS: Our analyses suggest that the prevention paradox is valid for
      adolescent boys and girls aged >=15 years and applies to a large range of alcohol
      related problems of varying severity. Our results imply that not only that
      prevention directed at all adolescents is essential, but also that HED should be
      particularly noticed.

PMID- 22366387
TI  - Knowledge and attitudes on pandemic and seasonal influenza vaccination among
      Slovenian physicians and dentists.
AB  - BACKGROUND: The aim of our study was to determine vaccination coverage among
      Slovenian physicians and dentists and assess their knowledge and attitudes
      regarding the pandemic and seasonal influenza vaccine. METHODS: In February 2010,
      an anonymous, self-administered questionnaire was developed and sent to all
      practising physicians and dentists in Slovenia. RESULTS: Out of 7092
      physicians/dentists, 1718 (24%) completed the questionnaire and 41.7% of the
      respondents were vaccinated against pandemic and seasonal influenza, while 58.3%
      of the study participants decided not to adhere to the recommendation: 15.6%
      received the pandemic vaccine only, 10.1% the seasonal vaccine only and 32.4%
      were not vaccinated at all. Acceptance of the pandemic and seasonal influenza
      vaccine was determined by higher age, being an internal medical trainee or
      specialist, working in a hospital, performing any kind of vaccination and having
      a chronic disease. Unvaccinated participants were more often working in out
      patient clinics, were without a specialty, were dentists and were not performing
      any vaccinations. Those who declined vaccination believed that they did not need
      to be vaccinated, had safety concerns and were afraid of side effects.
      Physicians/dentists vaccinated against pandemic and seasonal influenza had better
      knowledge and a more positive attitude towards the issue compared with their non
      vaccinated colleagues. CONCLUSIONS: Education on the efficacy and safety of
      vaccines should be one of the priority public health measures taken to improve
      knowledge and eliminate misconceptions and attitudinal barriers regarding
      immunization in physicians and dentists.

PMID- 22366388
TI  - Central pancreatectomy for benign or borderline lesions of the pancreatic neck: a
      single centre experience and literature review.
AB  - BACKGROUND/AIMS: To investigate the effectiveness and safety of central
      pancreatectomy. METHODOLOGY: We retrospectively studied 44 cases that underwent
      central pancreatectomy (CP), 55 patients who underwent distal pancreatectomy
      (DP), and 62 patients who underwent pancreatoduodenectomy (PD) for their benign
      or borderline pancreatic lesions; as well as the different management styles for
      pancreatic stumps in CP. RESULTS: The duration of surgery and length of hospital
      stay were shorter in the CP group than that of PD group, and blood loss was also
      less in CP group. There were no differences between the CP and DP groups in
      duration of surgery, length of hospital stay, and blood loss. The incidence of
      common surgical complications was higher in the PD group. There were more
      pancreatic fistulas (grade B/C) in CP and PD groups compared to that of the DP
      group. New onset or worsening of diabetes occurred only in the CP and PD groups
      at 4.8% and 10.9%, respectively. A pancreaticogastrostomy for distal pancreatic
      stumps reduced the incidence of pancreatic fistula (p=0.038). Duct-to-mucosa
      anastomosis had less pancreatic fistula than invagination anastomosis (p=0.017).
      There was no difference in incidence of pancreatic fistula between
      pancreaticojejunostomy and oversewing of proximal pancreatic stumps (p=0.601).
      CONCLUSIONS: CP is an available and safe operation for benign or borderline
      lesions located in the pancreatic neck. A pancreaticogastrostomy for distal
      pancreatic stumps or duct-to-mucosa anastomosis may reduce the risk of pancreatic
      fistula.

PMID- 22366389
TI  - The impact of glucocorticoids for cirrhosis patients performed major liver
      resection: a retrospective control study.
AB  - BACKGROUND/AIMS: Research on the influence of pre-operation usage of steroids for
      liver cirrhosis patients performed major liver resection (=3 segments).
      METHODOLOGY: In total, 741 cirrhosis patients who underwent major hepatectomy (>3
      segments) in our medical center were selected for the study. One hundred and five
      out of 741 patients used 500 mg methylprednisolone between half an hour and one
      hour before operation and were enrolled in the steroids group. The other 636
      patients without steroid injection were assigned in the control group. Our
      analysis compared the data of bilirubin, ALT, AST, postoperative PT,
      complications, mortality, IL-6, average length of hospitalization and the like.
      RESULTS: Blood sample test showed level of bilirubin and aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) and prothrombin time
      (PT), IL-6 were significantly lower in the steroids group than the control group
      in the postoperative days. There were no differences of mortality, morbidity and
      length of stay between the two groups. CONCLUSIONS: Methylprednisolone used in
      preoperative period could degrade the bilirubin and IL-6 level safely and
      effectively after operation but does not reduce the mortality and the average
      hospital stay for liver sclerotic patients with normal liver function with slight
      side effects; it may have positive clinical effects for marginal liver patients.

PMID- 22366390
TI  - Morphological features of early gallbladder carcinoma.
AB  - BACKGROUND/AIMS: This study aimed to clarify the morphological features of early
      gallbladder carcinoma including tumors invading the lamina propria (pT1a) or
      muscular layer (pT1b). METHODOLOGY: This retrospective study involved 299
      patients with early gallbladder carcinomas, identified from a surgical pathology
      database covering 29 years from 1982 through 2010. The macroscopic appearance of
      the tumor was classified as protruding (n=107, 36%) or superficial (n=192, 64%).
      Protruding tumors were subdivided into pedunculated or sessile, whereas
      superficial tumors were subdivided into elevated, flat or depressed. RESULTS:
      Eighty-four of 107 protruding tumors (79%) were detected preoperatively and/or
      intraoperatively, whereas only 47 of 192 superficial tumors (24%) were detected
      in this manner (p<0.001). Of the 107 protruding tumors, 21 were pedunculated and
      86 were sessile; 76 of these sessile tumors (88%) were accompanied by superficial
      elevated and/or flat tumors. In total, 257 patients (86%) had pT1a tumors and 42
      (14%) had pT1b tumors. No patient had evidence of lymphatic/blood vessel or
      perineural invasion or nodal metastasis on histology, except for lymphatic vessel
      invasion in one patient with a pT1b tumor. CONCLUSIONS: Two-thirds of early
      gallbladder carcinomas are classified as superficial. Most pT1b gallbladder
      carcinomas spread only locally.

PMID- 22366391
TI  - The Trypanosoma brucei CCCH zinc finger proteins ZC3H12 and ZC3H13.
AB  - CCCH-type zinc finger proteins have various roles in RNA metabolism. We here
      analysed the functional relevance of two such proteins from Trypanosoma brucei,
      TbZC3H12 and TbZC3H13. Each protein has a single CCCH motif very similar to those
      seen in metazoan proteins that regulate mRNA degradation. TbZC3H12 is expressed
      in bloodstream form parasites at low levels. It is phosphorylated, cytosolic and
      not required for normal growth of cultured bloodstream trypanosomes. RNA
      interference targeting TbZC3H13, on a TbZC3H12 null background, also had no
      effect on bloodstream trypanosome growth, but over-expression of tagged TbZC3H13
      inhibited procyclic trypanosome growth. Tandem affinity purification of both
      proteins revealed various interesting potential interactions; specificity was
      assessed against a list of proteins that were found in 24 other pull-down
      experiments, which is provided. The conservation of TbZC3H12 in all
      kinetoplastids, and TbZC3H13 in Salivaria, suggests that the two proteins may be
      required for optimal growth at some stage of the parasite life-cycle.

PMID- 22366392
TI  - [French clinical guidelines for prevention of perianaesthetic dental injuries.
      Short text].

PMID- 22366393
TI  - A review of parenting and adolescent sexual behavior: the moderating role of
      gender.
AB  - In spite of the established link between parenting and adolescent sexual risk
      behavior, less is known about the role of adolescent gender as a potential
      moderator of this association. This literature review integrates findings from 24
      studies to examine gender as a moderator of the link between parenting and youth
      sexual risk behavior. Despite the wide variability in methodology across the
      reviewed studies, findings suggest that monitoring may be more protective against
      sexual risk behavior for boys than girls, whereas parental warmth and emotional
      connection may be an especially salient factor for girls. The results of this
      review support further research on gender as an important factor in better
      understanding the role of parenting in the development of adolescent sexual
      behavior. Furthermore, the findings highlight the potential role of gender
      specific, tailored family-focused prevention programs targeting sexual behavior.

PMID- 22366394
TI  - Prognostic factors for survival following emergency Hartmann's procedure.
AB  - INTRODUCTION: Patients presenting with peritonitis require rapid treatment
      initiation including laparotomy. In the older population, this often leads to
      Hartmann's procedure being performed. The decision to perform surgery may be a
      difficult, multidisciplinary decision balancing premorbid comorbidity and quality
      of life with knowledge of the postoperative outcome. However, the evidence for
      survival outcome of emergency surgery based on age is lacking. The aim of this
      study was therefore to assess the survival implication of age and other
      prognostic factors on the outcome after Hartmann's procedure. METHODS: A
      retrospective review of prospectively collected data of all patients undergoing
      emergency (National Confidential Enquiry into Patient Outcome and Death category
      1-3) Hartmann's procedure in one NHS Health Board over a 5-year period. RESULTS:
      129 patients underwent Hartmann's procedure between November 2004 and November
      2009. The largest group, 61 patients (47.3%) had the procedure performed for
      perforated sigmoid diverticular disease. When examined at 5-year stratifications
      around the median, the most significant survival difference was seen at the age
      of 75 years (log rank chi(2) 11.246, p=0.001). Patients over 75 years had median
      survival significantly lower than those aged <75 years (p<0.001). However, Cox
      regression analysis showed that preoperative American Society of
      Anesthesiologists (ASA) status and haemoglobin were more significant independent
      predictors of mortality than this age strata (p=0.001 and 0.045 vs 0.660,
      respectively), adjusting for diagnosis. DISCUSSION: ASA grade and common blood
      abnormalities were more predictive of mortality after Hartmann's procedure than
      the most significant age stratification. Furthermore, age was not independently
      associated with survival. It would therefore be unreasonable to refuse Hartmann's
      procedure based on an age alone.

PMID- 22366395
TI  - Outpatient parenteral antibiotic therapy for infective endocarditis: a review of
      4 years' experience at a UK centre.
AB  - OBJECTIVES: To review the role of outpatient parenteral antibiotic therapy (OPAT)
      in the management of infective endocarditis (IE) with the aim to guide further
      development of the service modality both locally and at other centres, in light
      of the evolving recommendations on patient suitability in international
      guidelines. METHODS: A retrospective case review of all patients receiving OPAT
      for IE in Sheffield between January 2006 and October 2010 was conducted. Data
      were collected on site and microbiology of infection, antibiotic regimens,
      adverse events during OPAT therapy and outcomes were studied. RESULTS: A total of
      36 episodes of IE were treated in 34 patients. All patients received initial
      treatment as inpatients. Treatment was successful in 34/36 episodes (94.4%) with
      no evidence of recurrence at a median of 30 months follow-up. One patient had a
      relapse 2 months after completion of OPAT for enterococcal endocarditis and was
      found to have concurrent chronic prostatitis. One patient died of a ruptured
      pulmonary root abscess while receiving OPAT. Adverse events occurred in 12
      episodes (33.3%), of which seven were line associated. In four cases adverse
      events resulted in re-hospitalisation. A successful outcome was achieved in 22/24
      episodes (91.7%) deemed to be less suitable for OPAT due to higher risk of
      complications by Infectious Diseases Society of America guidelines. CONCLUSIONS:
      OPAT is a safe and effective means of completing therapy for IE, including
      prosthetic valve endocarditis and other cases at a higher risk of complicated
      disease. However, the relatively high rate of adverse events highlights the need
      for well-developed protocols and policies for patient selection and follow-up
      within the context of a formal OPAT service.

PMID- 22366396
TI  - alpha-Lipoic acid increases tolerance of cardiomyoblasts to glucose/glucose
      oxidase-induced injury via ROS-dependent ERK1/2 activation.
AB  - alpha-Lipoic acid (LA) has been shown to improve the diabetic cardiac symptoms.
      However, the underlying mechanisms have not been elucidated precisely. We have
      reported recently that LA potentially protected neurons from substance-induced
      apoptosis. We hypothesized that LA could attenuate cardiac cells death induced by
      oxidative stress derived from high glucose. To test this possibility, we examined
      the effects of LA on d-glucose/glucose oxidase (DG/GO, 30mM/5mU)-induced injury
      in rat cardiomyoblast H9c2 cells. We observed that LA pretreatment significantly
      increased cell viability in DG/GO-challenged cells. LA pretreatment also
      attenuated DG/GO-induced apoptosis as evidenced by decreases in both nuclear
      condensation and loss of mitochondrial potential. In addition, LA activated
      ERK1/2 and moderately increased ROS production. Blockade of ERK1/2 activation by
      PD98059 completely abolished LA-induced protection against DG/GO challenge.
      Inhibition of ROS by N-acetylcysteine abrogated LA-induced ERK1/2 activation and
      cytoprotection. Furthermore, we observed that the ROS production induced by LA
      was significantly slower and milder than that by DG/GO. Our results suggest that
      pretreatment with LA moderately increased ROS production to induce a
      preconditioning-like effect by ERK1/2 activation thereby increased tolerance of
      H9c2 cells to DG/GO challenge.

PMID- 22366397
TI  - Adolescent nonmedical users of prescription opioids: brief screening and
      substance use disorders.
AB  - OBJECTIVES: The objectives of this study are to examine the associations among a
      positive score on the CRAFFT (a substance use brief screening test for
      adolescents) and demographic characteristics, diversion sources, routes of
      administration, substance use behaviors and motivations associated with the use
      of prescription opioids without a legal prescription. METHODS: In 2009-2010, a
      sample of 2744 middle and high school students from two Midwestern school
      districts in the United States self-administered a Web-based survey. RESULTS:
      Approximately 5.6% (n=148) of respondents reported past-year nonmedical use of
      prescription opioids (NMUPO). Of those reporting NMUPO, approximately 35.1%
      (n=52) screened positive for substance use disorders based on the CRAFFT.
      Multiple logistic regression analyses indicated that the odds of buying
      prescription opioids, obtaining opioids from multiple diversion sources,
      administering opioids intranasally, and using opioids to get high were greater
      for nonmedical users with a positive CRAFFT screen as compared to NMUPO with a
      negative CRAFFT screen. NMUPO with a positive screen was motivated primarily for
      recreational purposes, while NMUPO with a negative screen was motivated almost
      exclusively by pain relief. CONCLUSIONS: The CRAFFT brief screening test for
      adolescents can be used to identify a subgroup of NMUPO at the highest risk for a
      substance use disorder as well as a subgroup of NMUPO who would benefit from
      appropriate pain management.

PMID- 22366398
TI  - Prevalence, awareness, and treatment of osteoporosis among Korean women: The
      Fourth Korea National Health and Nutrition Examination Survey.
AB  - PURPOSE: This study aimed to assess the factors associated with the prevalence,
      awareness, and treatment of osteoporosis in a representative sample of Korean
      women. METHODS: Data were obtained from dual energy X-ray absorptiometry
      measurement of the lumbar vertebrae and femoral neck, and from a standardized
      questionnaire in 2870 Korean women aged 50years and older who participated in the
      Fourth Korea National Health and Nutrition Examination Survey 2008-2009.
      Osteoporosis was defined by World Health Organization T-score criteria, and
      awareness and treatment were defined by self-report of an osteoporosis diagnosis
      and self-report of current anti-osteoporotic medication use, respectively. We
      assessed the relationship between multiple risk factors and prevalence,
      awareness, and treatment. RESULTS: Osteoporosis was reported in 39.1% of Korean
      women. Among those with osteoporosis, only 37.5% were aware of their diagnosis
      and 23.5% received pharmacological treatment. Despite higher prevalence among
      respondents who were older, of lower body weight, calcium intake, physical
      activity, and education levels, the awareness and treatment rates of these groups
      were similar or lower than that of the low-risk controls in multivariate logistic
      regression models. Moreover, easily identifiable risk factors (e.g., history of
      fracture, falls, height loss, familial osteoporosis) were not associated with
      awareness and treatment. Participants who had undergone health screening in the
      previous 2years exhibited increased awareness and treatment rates independently
      of other demographic factors. CONCLUSIONS: Osteoporosis was highly prevalent in
      this Korean study but was underdiagnosed and undertreated. Routine health
      screenings could be an effective strategy to increase osteoporosis awareness and
      treatment.

PMID- 22366399
TI  - Ubc9 negatively regulates BMP-mediated osteoblastic differentiation in cultured
      cells.
AB  - SUMO (small ubiquitin-related modifier) modification (SUMOylation) has been
      reported to regulate various biological events such as cell-cycle progression,
      proliferation, and survival. Bone morphogenetic proteins (BMPs) play an important
      role in osteoblast differentiation and maturation. Although Smad4, which acts as
      a transcriptional factor in the BMP signaling, is a target of SUMOylation, the
      involvement of SUMOylation in osteoblast differentiation remains unclear. In this
      report, we demonstrated spatial expression patterns of SUMO proteins and Ubc9
      (ubiquitin conjugating enzyme 9), which is a unique E2-SUMOylation enzyme, in
      mouse tibia. Furthermore, siRNA knockdown of Ubc9 enhanced osteoblastic
      differentiation induced by BMP2 in C2C12 mouse myoblasts and ST2 mouse bone
      marrow derived stromal cells. Ubc9 knockdown elevated the BMP signaling
      transduction and reduced the expression of muscle-related genes in cooperation
      with BMP2. Finally, a luciferase assay using an Id1 (target gene of BMP
      signaling) reporter revealed that Smad4 mutants prevented from SUMOylation at
      their Lys158 possessed more potent transcriptional activity than wild-type Smad4.
      Taken together, these findings suggest that Ubc9 negatively regulates
      osteoblastic differentiation induced by BMP via, at least in part, SUMOylation of
      Smad4.

PMID- 22366400
TI  - Combination therapy with eldecalcitol and alendronate has therapeutic advantages
      over monotherapy by improving bone strength.
AB  - Eldecalcitol (ED-71), a 2beta-hydroxypropyloxy derivative of
      1alpha,25(OH)(2)D(3), inhibits bone resorption more potently than does
      alfacalcidol while maintaining osteoblastic function in an estrogen-deficient,
      high-turnover osteoporosis rat model. Alendronate (ALN) has been reported to
      increase bone mass by suppressing bone resorption mainly by inducing apoptosis of
      osteoclasts. The aim of this study was to clarify the combination effect of ED-71
      and ALN on bone loss in ovariectomized rats. Wistar-Imamichi rats (32weeks old)
      were ovariectomized and randomly assigned to 10 groups (n=9-11); 11 rats were
      sham-operated. Rats were orally administered either vehicle alone, ALN (0.05,
      0.2mg/kg), ED-71 (0.015, 0.03MUg/kg), or a combination of ALN and ED-71. The
      treatment started 2weeks after surgery and continued for 12weeks. ED-71
      significantly increased calcium and phosphorus in serum and urine; however, the
      mean values were within the normal range. Bone mineral density (BMD) and maximum
      load in both the lumbar spine and femur significantly increased with ED-71
      monotherapy, and showed a tendency to increase with ALN monotherapy. Compared
      with ALN monotherapy, the combination of ALN and ED-71 significantly increased
      BMD and maximum load in both the lumbar spine and femur, suggesting that the
      combination therapy is more beneficial than ALN monotherapy in this protocol. The
      combination treatment had an additive suppressive effect on eroded surface and
      osteoclast number, with the suppressive effect more potent than either ALN or ED
      71 monotherapy. Moreover, the combination therapy partially counteracted the
      suppressive effects of ALN on bone formation and on the histomorphometric indices
      of osteoblast number and activity. Interestingly, ALN had no effect on the
      anabolic action of ED-71. In conclusion, the combination therapy of ALN and ED-71
      has therapeutic advantages over ALN monotherapy in terms of improving bone
      mechanical strength without excessive suppression of bone turnover.

PMID- 22366401
TI  - Beyond a reasonable doubt? Bisphosphonates and atypical femur fractures.
AB  - In May 2011, we were privileged to debate on behalf of the ECTS and the ASBMR in
      a Clinical Debate hosted by the IBMS and the ECTS with the motion "Atypical
      femoral shaft fractures are a consequence of bisphosphonate therapy". The
      evidence presented for and against the motion is summarized and discussed in this
      joint commentary. The hypothetical chain of evidence between bisphosphonates,
      decreased toughness of bone, microcrack accumulation in man and atypical
      fractures is plausible but unproven. However, the combination of consistent
      clinical features (which may include a stress reaction at the site of maximum
      tensile load), a significant statistical association and a feasible biological
      mechanism gives grounds for caution especially as regards long term treatment in
      patients at low or moderate risk of osteoporotic fractures.

PMID- 22366402
TI  - Spinal cord clinical trials and the role for bioengineering.
AB  - There is considerable need for bringing effective therapies for spinal cord
      injury (SCI) to the clinic. Excellent medical and surgical management has
      mitigated poor prognoses after SCI; however, few advances have been made to
      return lost function. Bioengineering approaches have shown great promise in
      preclinical rodent models, yet there remains a large translational gap to carry
      these forward in human trials. Herein, we provide a framework of human clinical
      trials, an overview of past trials for SCI, as well as bioengineered approaches
      that include: directly applied pharmacologics, cellular transplantation,
      biomaterials and functional neurorehabilitation. Success of novel therapies will
      require the correct application of comprehensive preclinical studies with well
      designed and expertly conducted human clinical trials. While biologics and
      bioengineered strategies are widely considered to represent the high potential
      benefits for those who have sustained a spinal injury, few such therapies have
      been thoroughly tested with appreciable efficacy for use in human SCI. With these
      considerations, we propose that bioengineered strategies are poised to enter
      clinical trials.

PMID- 22366403
TI  - Advances in natural biomaterials for nerve tissue repair.
AB  - Natural biomaterials are well positioned to play a significant role in the
      development of the next generation of biomaterials for nervous system repair.
      These materials are derived from naturally occurring substances and are highly
      diverse and versatile. They are generally biocompatible and are well tolerated in
      vivo, and therefore have a high potential to be successful as part of clinical
      repair strategies in the nervous system. Here we review recent reports on
      acellular tissue grafts, collagen, hyaluronan, fibrin, and agarose in their use
      to repair the nervous system. In addition, newly developed advanced fabrication
      techniques to further develop the next generation natural biomaterials-based
      therapeutic devices are discussed.

PMID- 22366404
TI  - The combination of interleukin-10 -1082 and tumor necrosis factor alpha -308 or
      interleukin-6 -174 genes polymorphisms suggests an association with
      susceptibility to Hashimoto's thyroiditis.
AB  - BACKGROUND: The etiopathogenesis of Hashimoto's thyroiditis (HT) has not been
      clearly elucidated although the role of chronical inflammation and endothelial
      dysfunction has been established. The imbalance between pro- and anti
      inflammatory cytokines may play a role in the etiology. The aim of the present
      study was to investigate whether cytokine gene polymorphisms are associated with
      HT, and to evaluate the relationship between genotypes and clinical/laboratory
      manifestation of HT. METHODS: Tumor necrosis factor alpha (TNFalpha) G-308A (rs
      1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 G-1082A (rs 1800896)
      single nucleotide polymorphisms (SNPs) in DNA from peripheral blood leukocytes of
      190 patients with HT and 231 healthy controls were investigated by real-time PCR
      combined with melting curve analysis using fluorescence-labeled hybridization
      probes. RESULTS: There was no notable risk for HT afflicted by TNFalpha -308, IL
      6 -174 and IL-10 -1082 polymorphisms alone. However, carriers of variant alleles
      of both IL-10 -1082 and TNFalpha -308 polymorphisms had four-fold times higher
      risk for HT in comparison with non-carriers. Additionally, concomitant presence
      of both mutant IL-10 -1082 A and IL-6 -174 C alleles raised three-fold the HT
      risk. CONCLUSION: Our results suggest that the combined effects of TNFalpha -308,
      IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce
      functional differences and modify the risk for HT.

PMID- 22366406
TI  - Immunomodulatory studies of a bioactive fraction from the fruit of Prunus cerasus
      in BALB/c mice.
AB  - In order to evaluate the role of ethyl acetate fraction (PNRS-EtOAC) obtained
      from the Prunus cerasus fruit in the modulation of immune responses, detailed
      studies were carried out using a panel of in vivo assays. Oral administration of
      PNRS-EtOAC (25-100 mg/kg) stimulated the IgM and IgG titre expressed in the form
      of hemagglutination antibody (HA) titre. Further, it elicited a dose related
      increase in the delayed type hypersensitivity reaction (DTH) after 24 and 48 h in
      BALB/c mice. Besides augmenting the humoral and cell mediated immune response,
      the concentration of cytokines (IFN-gamma, IL-4, and TNF-alpha) in serum with
      respect to T cell interactions, i.e. the proliferation of lymphocytes were
      significantly increased at 50 mg/kg compared with the control. The results in
      these studies demonstrated the immunostimulatory effect of PNRS-EtOAC in a dose
      dependent manner with respect to the macrophage activation possibly expressing
      the phagocytosis and nitrite production by the enhancement of TNF-alpha
      production as a mode of action.

PMID- 22366407
TI  - Liver transplantation for alcoholic hepatitis.

PMID- 22366405
TI  - The protein LJM 111 from Lutzomyia longipalpis salivary gland extract (SGE)
      accounts for the SGE-inhibitory effects upon inflammatory parameters in
      experimental arthritis model.
AB  - Several studies have pointed out the immunomodulatory properties of the Salivary
      Gland Extract (SGE) from Lutzomyia longipalpis. We aimed to identify the SGE
      component (s) responsible for its effect on ovalbumin (OVA)-induced neutrophil
      migration (NM) and to evaluate the effect of SGE and components in the antigen
      induced arthritis (AIA) model. We tested the anti-arthritic activities of SGE and
      the recombinant LJM111 salivary protein (rLJM111) by measuring the mechanical
      hypernociception and the NM into synovial cavity. Furthermore, we measured IL-17,
      TNF-alpha and IFN-gamma released by lymph nodes cells stimulated with mBSA or
      anti-CD3 using enzyme-linked immunosorbent assay (ELISA). Additionally, we tested
      the effect of SGE and rLJM111 on co-stimulatory molecules expression (MHC-II and
      CD-86) by flow cytometry, TNF-alpha and IL-10 production (ELISA) of bone marrow
      derived dendritic cells (BMDCs) stimulated with LPS, chemotaxis and actin
      polymerization from neutrophils. Besides, the effect of SGE on CXCR2 and GRK-2
      expression on neutrophils was investigated. We identified one plasmid expressing
      the protein LJM111 that prevented NM in OVA-challenged immunized mice.
      Furthermore, both SGE and rLJM111 inhibited NM and pain sensitivity in AIA and
      reduced IL-17, TNF-alpha and IFN-gamma. SGE and rLJM111 also reduced MHC-II and
      CD-86 expression and TNF-alpha whereas increased IL-10 release by LPS-stimulated
      BMDCs. SGE, but not LJM 111, inhibited neutrophils chemotaxis and actin
      polymerization. Additionally, SGE reduced neutrophil CXCR2 expression and
      increased GRK-2. Thus, rLJM111 is partially responsible for SGE mechanisms by
      diminishing DC function and maturation but not chemoattraction of neutrophils.

PMID- 22366408
TI  - Induction of apoptosis in EMU-myc lymphoma cells in vitro and in vivo through
      calpain inhibition.
AB  - Calpains are cysteine proteases that have been implicated as both effectors and
      suppressors of apoptosis. Previously, we showed that c-myc transformation
      regulated calpain activity and sensitized cells to apoptosis induced by calpain
      inhibition. The objective of this study was to investigate the role of calpain in
      the EMU-myc transgenic model of B-cell lymphoma. Calpain activity assays,
      apoptosis, cell cycle assays, and expression measurements were used to determine
      the activity and role of calpain in vitro and in vivo. We found that EMU-myc
      transgenic cells have highly elevated calpain activity. Calpastatin, the negative
      calpain regulator, was expressed at much lower levels in EMU-myc lymphoma cells
      compared to normal splenic B cells. The primary isoform in EMU-myc lymphoma is
      calpain 1. Treatment of EMU-myc lymphoma cells with the calpain inhibitors
      PD150606 or calpain inhibitor III induced caspase-3-dependent apoptosis in vitro.
      General caspase inhibitors or caspase-3/7 inhibitor protected cells from death
      induced by calpain inhibitor, whereas caspase-9 inhibitors failed to rescue
      cells. Human Burkitt's lymphoma (BL2) cells display a pattern of sensitivity and
      caspase-3 dependence similar to calpain inhibition. Treatment of EMU-myc lymphoma
      bearing mice with PD150606 inhibited calpain activity in vivo and induced cell
      death in these cells as determined by terminal deoxynucleotide transferase
      mediated dUTP nick-end labeling staining. Multiple daily treatments resulted in
      reduced tumor load, particularly in combination with etoposide. In conclusion,
      calpain is highly elevated in the EMU-myc lymphoma and calpain inhibition has
      therapeutic potential.

PMID- 22366409
TI  - The importance of applying a sentinel lymph node mapping algorithm in endometrial
      cancer staging: beyond removal of blue nodes.
AB  - OBJECTIVE: To determine the false-negative rate of a surgical sentinel lymph node
      (SLN) mapping algorithm that incorporates more than just removing SLNs in
      detecting metastatic endometrial cancer. METHODS: A prospective database of all
      patients who underwent lymphatic mapping for endometrial cancer was reviewed.
      Cervical injection of blue dye was used in all cases. The surgical algorithm is
      as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal
      evaluation including excision of all mapped SLNs and suspicious nodes regardless
      of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific
      pelvic, common iliac, and interiliac lymph node dissection (LND) is performed.
      Paraaortic LND is performed at the attendings' discretion. The algorithm was
      retrospectively applied. RESULTS: From 9/2005 to 4/2011, 498 patients received a
      blue dye cervical injection for SLN mapping. At least one LN was removed in 95%
      of cases (474/498); at least one SLN was identified in 81% (401/498). SLN
      correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN
      mapped, resulting in a 15% false-negative rate. After applying the algorithm, the
      false-negative rate dropped to 2%. Only one patient, whose LN spread would not
      have been caught by the algorithm, had an isolated positive right paraaortic LN
      with a negative ipsilateral SLN and pelvic LND. CONCLUSIONS: Satisfactory SLN
      mapping in endometrial cancer requires adherence to a surgical SLN algorithm and
      goes beyond just the removal of blue SLNs. Removal of any suspicious node along
      with side-specific lymphadenectomy for failed mapping are an integral part of
      this algorithm. Further validation of the false-negative rate of this algorithm
      is necessary.

PMID- 22366410
TI  - Nomograms to predict isolated loco-regional or distant recurrence among women
      with uterine cancer.
AB  - OBJECTIVE: While there is ample literature on prognostic factors for uterine
      cancer, currently there are nomeans to estimate an individual's risk for
      recurrence or to differentiate the risk of loco-regional recurrence from distant
      recurrence. We addressed this gap by developing nomograms to individualize the
      risk of recurrence. METHODS: A total of 2097 consecutive patients who underwent
      primary surgery between 1997 and 2007 were included. Sixteen covariates were
      evaluated for their prognostic significance and modeled using multivariable
      competing risks regression to predict three-year outcomes as part of a nomogram.
      Each covariate in the nomogram is assigned a value, and a sum of these values
      form the overall risk score from which three-year incidence probabilities can be
      predicted for each individual. Predictive accuracy was assessed with concordance
      index and then corrected for optimism. RESULTS: The median follow-up time (inter
      quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a
      recurrence (127 patients with isolated loco-regional recurrence, 94 patients with
      distant recurrence). The nomograms included the following covariates: age at
      diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type,
      depth of myometrial invasion, and peritoneal cytology. Concordance indices for
      isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively.
      CONCLUSIONS: Our nomograms quantify an individual patient's risk of isolated loco
      regional and distant recurrence, using factors that are routinely collected. They
      may assist clinicians to assess an individual's prognosis, individualize
      treatment and also assist in the risk stratification in prospective randomized
      clinical trials evaluating the effectiveness of treatments for uterine cancer.

PMID- 22366412
TI  - DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced
      DNA damage and apoptosis in human embryo lung fibroblast cells.
AB  - When cells encounter genotoxic stress, sensors for DNA lesions stabilize and
      activate p53; the signals involved, however, are largely unclear. Inorganic
      arsenite is a ubiquitous environmental contaminant associated with an increased
      risk of lung and skin damage and cancer. Although DNA double-strand breaks and
      apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism
      of action remains obscure. Here, we find that, in human embryo lung fibroblast
      (HELF) cells, arsenite induces the activation of dependent protein kinase
      catalytic subunit (DNA-PKcs), which then phosphorylates and activates c-Jun N
      terminal kinases 2 (JNK2), but not JNK1. As a positive regulator of p53, JNK2
      binds to p53 and prevents p53 from murine double minute 2 (mdm2)-mediated,
      ubiquitin-proteasome-dependent degradation. Knockdown of DNA-PKcs/JNK2 signal
      pathway or p53 reduces apoptosis but elevates the DNA damage induced by a high
      level of arsenite. These results suggest that DNA-PKcs-mediated stabilization of
      p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis.

PMID- 22366413
TI  - Bio-silica and bio-polyphosphate: applications in biomedicine (bone formation).
AB  - Bio-silica represents the main mineral component of the sponge skeletal elements
      (siliceous spicules), while bio-polyphosphate (bio-polyP), a multifunctional
      polymer existing in microorganisms and animals acts, among others, as
      reinforcement for pores in cell membranes. These natural inorganic bio-polymers,
      which can be readily prepared, either by recombinant enzymes (bio-silica and bio
      polyP) or chemically (polyP), are promising materials/substances for the
      amelioration and/or treatment of human bone diseases and dysfunctions. It has
      been demonstrated that bio-silica causes in vitro a differential effect on the
      expression of the genes OPG and RANKL, encoding two mediators that control the
      tuned interaction of the anabolic (osteoblasts) and catabolic (osteoclasts)
      pathways in human bone cells. Since bio-silica and bio-polyP also induce the
      expression of the key mediator BMP2 which directs the differentiation of bone
      forming progenitor cells to mature osteoblasts and in parallel inhibits the
      function of osteoclasts, they are promising candidates for treatment of
      osteoporosis.

PMID- 22366414
TI  - Role of the NiFe hydrogenase Hya in oxidative stress defense in Geobacter
      sulfurreducens.
AB  - Geobacter sulfurreducens, an Fe(III)-reducing deltaproteobacterium found in
      anoxic subsurface environments, contains 4 NiFe hydrogenases. Hyb, a
      periplasmically oriented membrane-bound NiFe hydrogenase, is essential for
      hydrogen-dependent growth. The functions of the three other hydrogenases are
      unknown. We show here that the other periplasmically oriented membrane-bound NiFe
      hydrogenase, Hya, is necessary for growth after exposure to oxidative stress when
      hydrogen or a highly limiting concentration of acetate is the electron source.
      The beneficial impact of Hya on growth was dependent on the presence of H(2) in
      the atmosphere. Moreover, the Hya-deficient strain was more sensitive to the
      presence of superoxide or hydrogen peroxide. Hya was also required to safeguard
      Hyb hydrogen oxidation activity after exposure to O(2). Overexpression studies
      demonstrated that Hya was more resistant to oxidative stress than Hyb.
      Overexpression of Hya also resulted in the creation of a recombinant strain
      better fitted for exposure to oxidative stress than wild-type G. sulfurreducens.
      These results demonstrate that one of the physiological roles of the O(2)
      resistant Hya is to participate in the oxidative stress defense of G.
      sulfurreducens.

PMID- 22366415
TI  - A stress-inducible quorum-sensing peptide mediates the formation of persister
      cells with noninherited multidrug tolerance.
AB  - Within a given microbial population, a small subpopulation known as dormant
      persister cells exists. This persistence property ensures the survival of the
      population as a whole in the presence of lethal factors. Although persisters are
      highly important in antibiotic therapy, the mechanism for persistence is still
      not thoroughly understood. We show here that the cariogenic organism
      Streptococcus mutans forms persister cells showing noninherited multidrug
      tolerance. We demonstrated that the ectopic expression of the type II toxin
      antitoxin systems, MazEF and RelBE, caused an increase in the number of
      persisters. In a search for additional persistence genes, an expression library
      was constructed, and several clones exhibiting a significant difference in
      persister formation after prolonged antibiotic treatment were selected. The
      candidate persister genes include genes involved in transcription/replication,
      sugar metabolism, cell wall synthesis, and energy metabolism, clearly pointing to
      redundant pathways for persister formation. We have previously reported that the
      S. mutans quorum-sensing peptide, CSP pheromone, was a stress-inducible alarmone
      capable of conveying sophisticated messages in the bacterial population. In this
      study, we demonstrate the involvement of the intraspecies quorum-sensing system
      during the formation of stress-induced multidrug-tolerant persisters. To the best
      of our knowledge, this is the first study reporting the induction of bacterial
      persistence using a quorum-sensing regulatory system.

PMID- 22366416
TI  - GntR-type transcriptional regulator PckR negatively regulates the expression of
      phosphoenolpyruvate carboxykinase in Corynebacterium glutamicum.
AB  - The pck (cg3169) gene of Corynebacterium glutamicum encodes a phosphoenolpyruvate
      carboxykinase (PEPCK). Here, a candidate transcriptional regulator that binds to
      the promoter region of pck was detected using a DNA affinity purification
      approach. An isolated protein was identified to be PckR (Cg0196), a GntR family
      transcriptional regulator which consists of 253 amino acids with a mass of 27 kDa
      as measured by peptide mass fingerprinting. The results of electrophoretic
      mobility shift assays verified that PckR specifically binds to the pck promoter.
      The putative regulator binding region extended from position -44 to -27 (an 18-bp
      sequence) relative to the transcriptional start point of the pck gene. We
      measured the expression of pck in a pckR deletion mutant by using quantitative
      real-time reverse transcription-PCR. The expression level of pck in the pckR
      mutant was 7.6 times higher than that in wild-type cells grown in glucose.
      Comparative DNA microarray hybridizations and bioinformatic searches revealed the
      gene composition of the transcriptional regulon of C. glutamicum. Based on these
      results, PckR seemed to play an important role in the regulation of PEPCK in C.
      glutamicum grown in glucose. In particular, these assays revealed that PckR acts
      as a repressor of pck expression during glucose metabolism.

PMID- 22366417
TI  - Physiological and proteomic adaptation of "Aromatoleum aromaticum" EbN1 to low
      growth rates in benzoate-limited, anoxic chemostats.
AB  - "Aromatoleum aromaticum" EbN1 was cultivated at different growth rates in
      benzoate-limited chemostats under nitrate-reducing conditions. Physiological
      characteristics, proteome dynamics, phospholipid-linked fatty acid (PLFA)
      composition, and poly(3-hydroxybutyrate) (PHB) content were analyzed in steady
      state cells at low (MU(low)) (0.036 h(-1)), medium (MU(med)) (0.108 h(-1)), and
      high (MU(high)) (0.180 h(-1)) growth rates. A positive correlation to growth rate
      was observed for cellular parameters (cell size, and DNA and protein contents).
      The free energy consumed for biomass formation steadily increased with growth
      rate. In contrast, the energy demand for maintenance increased only from MU(low)
      to MU(med) and then remained constant until MU(high). The most comprehensive
      proteomic changes were observed at MU(low) compared to MU(high). Uniformly
      decreased abundances of protein components of the anaerobic benzoyl coenzyme A
      (benzoyl-CoA) pathway, central carbon metabolism, and information processing
      agree with a general deceleration of benzoate metabolism and cellular processes
      in response to slow growth. In contrast, increased abundances were observed at
      MU(low) for diverse catabolic proteins and components of uptake systems in the
      absence of the respective substrate (aromatic or aliphatic compounds) and for
      proteins involved in stress responses. This potential catabolic versatility and
      stress defense during slow growth may be interpreted as preparation for future
      needs.

PMID- 22366418
TI  - A VapBC toxin-antitoxin module is a posttranscriptional regulator of metabolic
      flux in mycobacteria.
AB  - The largest family of toxin-antitoxin (TA) modules are encoded by the vapBC
      operons, but their roles in bacterial physiology remain enigmatic. Microarray
      analysis in Mycobacterium smegmatis overexpressing VapC/VapBC revealed a high
      percentage of downregulated genes with annotated roles in carbon transport and
      metabolism, suggesting that VapC was targeting specific metabolic mRNA
      transcripts. To validate this hypothesis, purified VapC was used to identify the
      RNA cleavage site in vitro. VapC had RNase activity that was sequence specific,
      cleaving single-stranded RNA substrates at AUAU and AUAA in vitro and in vivo
      (viz., MSMEG_2121 to MSMEG_2124). A bioinformatic analysis of these regions
      suggested that an RNA hairpin 3' of the AUA(U/A) motif is also required for
      efficient cleavage. VapC-mediated regulation in vivo was demonstrated by showing
      that MSMEG_2124 (dhaF) and MSMEG_2121 (dhaM) were upregulated in a DeltavapBC
      mutant growing on glycerol. The DeltavapBC mutant had a specific rate of glycerol
      consumption that was 2.4-fold higher than that of the wild type during
      exponential growth. This increased rate of glycerol consumption was not used for
      generating bacterial biomass, suggesting that metabolism by the DeltavapBC mutant
      was uncoupled from growth. These data suggest a model in which VapC regulates the
      rate of glycerol utilization to match the anabolic demands of the cell, allowing
      for fine-tuning of the catabolic rate at a posttranscriptional level.

PMID- 22366419
TI  - Prevalence and detailed mapping of the gonococcal genetic island in Neisseria
      meningitidis.
AB  - The 57-kb gonococcal genetic island (GGI) encodes a type IV secretion system
      (T4SS) that is found in most strains of N. gonorrhoeae. This T4SS functions to
      secrete single-stranded DNA that is active in natural transformation. The GGI has
      also been found in some strains of N. meningitidis. We screened 126 isolates of
      N. meningitidis and found the GGI in 17.5% of strains, with the prevalence
      varying widely among serogroups. The GGI is found in a significant number of
      serogroup C, W-135, and X strains but was not found in strains of serogroup A, B,
      or Y. Through detailed PCR mapping and DNA sequencing, we identified five
      distinct GGI types in meningococci. DNA sequencing and a genetic assay revealed
      that the GGI was likely integrated into the meningococcal chromosome by the site
      specific recombinase XerCD and that the GGI can be excised and lost from the
      genome. Functional studies showed that in contrast with the gonococcal T4SS, the
      meningococcal T4SS does not secrete DNA, nor does it confer Ton-independent
      intracellular survival. Deletion of T4SS genes did not affect association with or
      invasion of host cells. These results demonstrate that the GGI is found in a
      significant proportion of meningococcal strains and that while some strains carry
      multiple insertions and deletions in the GGI, other strains carry intact T4SS
      genes and may produce functional secretion systems.

PMID- 22366420
TI  - A better understanding of what makes some proteins "fat".

PMID- 22366421
TI  - Repression of Salmonella enterica phoP expression by small molecules from
      physiological bile.
AB  - Infection with Salmonella enterica serovar Typhi in humans causes the life
      threatening disease typhoid fever. In the laboratory, typhoid fever can be
      modeled through the inoculation of susceptible mice with Salmonella enterica
      serovar Typhimurium. Using this murine model, we previously characterized the
      interactions between Salmonella Typhimurium and host cells in the gallbladder and
      showed that this pathogen can successfully invade gallbladder epithelial cells
      and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile
      phospholipids to grow at high rates. These abilities are likely important for
      quick colonization of the gallbladder during typhoid fever and further pathogen
      dissemination through fecal shedding. To further characterize the interactions
      between Salmonella and the gallbladder environment, we compared the
      transcriptomes of Salmonella cultures grown in LB broth or physiological murine
      bile. Our data showed that many genes involved in bacterial central metabolism
      are affected by bile, with the citric acid cycle being repressed and alternative
      respiratory systems being activated. Additionally, our study revealed a new
      aspect of Salmonella interactions with bile through the identification of the
      global regulator phoP as a bile-responsive gene. Repression of phoP expression
      could also be achieved using physiological, but not commercial, bovine bile. The
      biological activity does not involve PhoPQ sensing of a bile component and is not
      caused by bile acids, the most abundant organic components of bile. Bioactivity
      guided purification allowed the identification of a subset of small molecules
      from bile that can elicit full activity; however, a single compound with phoP
      inhibitory activity could not be isolated, suggesting that multiple molecules may
      act in synergy to achieve this effect. Due to the critical role of phoP in
      Salmonella virulence, further studies in this area will likely reveal aspects of
      the interaction between Salmonella and bile that are relevant to disease.

PMID- 22366423
TI  - Some physicochemical properties of two major soluble hepatic glutathione
      transferases of tilapia (Tilapia zilli).
AB  - Two distinct glutathione transferases from the liver of adult Tilapia zilli were
      identified and purified to apparent homogeneity by ion-exchange chromatography on
      DEAE-cellulose and by gel filtration on Sephadex G-150. These major GST forms
      labeled tzGST1 and tzGST2 accounted for approximately 42% of the activity
      detectable with 1-chloro-2,4-dinitrobenzene (CDNB) as a typical electrophilic
      substrate. Apparent subunit and molecular mass values, substrate specificities
      and sensitivity to inhibitors as well as kinetic studies were used to
      differentiate the GST forms. SDS/PAGE indicated subunit molecular masses of 22.0
      kDa (tzGST1) and 26.1 kDa (tzGST2) while native molecular weight by gel
      filtration on sephadex G-100 indicated native molecular masses of 46.8 kDa and
      48.0 kDa for tzGST1 and tzGST2 respectively. They appeared to be homodimers.
      Inhibition studies showed that tzGST1 was more sensitive to ethacrynic acid (EA),
      hematin, tributyltinacetate (TBTA), triethyltinbromide (TETB), and
      triphenyltinchloride (TPTC) than tzGST2 with TPTC being the most potent
      inhibitor. T. zilli GSTs could conjugate CDNB, DCNB, rho-NBC, and EA with GSH but
      displayed no observable conjugating activity with NBDCl. The K(m) and V(max) for
      tzGST1 and tzGST2 with CDNB were 0.56 +/- 0.05 mM; 0.24 +/- 0.03 MUmol/min/ml and
      0.91 +/- 0.07 mM; 0.14 +/- 0.05 MUmol/min/ml respectively while K(m) and V(max)
      with GSH were 0.46 +/- 0.02 mM; 0.19 +/- 0.20 MUmol/min/ml and 1.32 +/- 0.15 mM;
      0.21 +/- 0.07 MUmol/min/ml respectively. Denaturation and renaturation studies
      with guanidine hydrochloride (Gdn-HCl) revealed that concentration of 4.0 M Gdn
      HCl completely denatured tzGST1 and the possible isoenzyme was able to renature
      to 92% of the original activity. The renaturation process was dependent on
      temperature. The outcome of this study indicated that tzGSTs are possible GST
      isoenzymes actively present and involve in the detoxification process in the
      liver of tilapia when the subject is exposed to chemical toxins. The wide range
      of chemical toxins encountered in the polluted environment may have directed the
      selection of multiple tilapia GST isoforms with broad substrate specificity via
      gene duplication. Consequently, tzGST1 has a better chemical toxin bio
      transforming capacity than tzGST2 due to its higher affinity for its substrates-
      a form of adaption to the polluted environment.

PMID- 22366422
TI  - Comparative analysis of the first complete Enterococcus faecium genome.
AB  - Vancomycin-resistant enterococci (VRE) are one of the leading causes of
      nosocomial infections in health care facilities around the globe. In particular,
      infections caused by vancomycin-resistant Enterococcus faecium are becoming
      increasingly common. Comparative and functional genomic studies of E. faecium
      isolates have so far been limited owing to the lack of a fully assembled E.
      faecium genome sequence. Here we address this issue and report the complete 3.0
      Mb genome sequence of the multilocus sequence type 17 vancomycin-resistant
      Enterococcus faecium strain Aus0004, isolated from the bloodstream of a patient
      in Melbourne, Australia, in 1998. The genome comprises a 2.9-Mb circular
      chromosome and three circular plasmids. The chromosome harbors putative E.
      faecium virulence factors such as enterococcal surface protein, hemolysin, and
      collagen-binding adhesin. Aus0004 has a very large accessory genome (38%) that
      includes three prophage and two genomic islands absent among 22 other E. faecium
      genomes. One of the prophage was present as inverted 50-kb repeats that appear to
      have facilitated a 683-kb chromosomal inversion across the replication terminus,
      resulting in a striking replichore imbalance. Other distinctive features include
      76 insertion sequence elements and a single chromosomal copy of Tn1549 containing
      the vanB vancomycin resistance element. A complete E. faecium genome will be a
      useful resource to assist our understanding of this emerging nosocomial pathogen.

PMID- 22366424
TI  - Combined effects of oestrogen receptor antagonists on in vitro vitellogenesis.
AB  - Some environmental compounds are known to have anti-oestrogenic activity and
      their modes of action (MoA) are believed to include competitive inhibition of
      17beta-estradiol (E2) binding to the oestrogen receptor (ER) or interference with
      ER-dependent processes. The presence of multiple compounds having the same MoA
      may cause concern, as exposure to multiple compounds at concentrations below
      their threshold for effect can interact with cellular targets to cause effects in
      combination. The combined effect of mixtures can be assessed using prediction
      models such as concentration addition (CA) and independent action (IA). The
      objective of the present study was to determine if the CA and IA prediction
      models could accurately characterise the combined effects of mixtures of ER
      antagonists in rainbow trout (Oncorhynchus mykiss) hepatocytes using the ER
      mediated production of the oestrogenic biomarker vitellogenin (Vtg) as a
      screening assay. Model anti-oestrogens (4-hydroxytamoxifen and ZM 189.154) and
      environmentally relevant compounds (PCBs and PAHs) were tested to ensure
      inclusion of compounds from different chemical classes and with different MoAs.
      All eleven tested compounds had the ability to reduce the in vitro E2-induced
      production of Vtg in a concentration-dependent manner. The potency of the tested
      compounds differed by four orders of magnitude based on the concentrations for
      50% inhibition (IC(50)). The observed order of potency was 2,3,7,8
      tetrachlorodibenzo-p-dioxin>4-hydroxytamoxifen>3,3',4,4',5
      pentachlorobiphenyl>benzo(k)fluoranthene>3,3',4,4'-tetrachlorobiphenyl>beta
      naphthoflavone>ZM 189.154>indeno[1,2,3
      cd]pyrene>benzo(b)fluoranthene>benzo(a)pyrene>benzo(a)anthracene. The CA and IA
      models were able to predict the combined effects of mixtures of ER antagonists
      with similar MoA. The mixtures of certain ER-antagonists with different and/or
      complex MoA caused deviations from both the CA and the IA model by causing higher
      anti-oestrogenic activity than predicted from the potency of the compounds alone.
      The rationale for these deviations warrants additional studies to assess the
      potential impacts on the health of organisms.

PMID- 22366425
TI  - Dechlorination of the dietary nona-chlorinated toxaphene congeners 62 and 50 into
      the octa-chlorinated toxaphene congeners 44 and 40 in zebrafish (Danio rerio) and
      Atlantic salmon (Salmo salar).
AB  - The relative feed-to-fish accumulation and possible biotransformation of the nona
      chlorinated toxaphene congeners currently included in EU-legislation (CHB-50 and 
      62) and the octa-chlorinated congeners recommended by the European Food Safety
      Authority to be included in future surveillance of fish samples (CHB-40, 41, and
      44) were investigated in the present study. Model fish Danio rerio were fed
      either (a) diets spiked with a combination as well as the pure individual
      toxaphene congeners CHB-50 or 62 or (b) diets spiked with the combination of CHB
      ?50+62 and/or CHB ?40+41+44. In addition, seawater adapted Atlantic salmon smolts
      were fed technical toxaphene enriched feeds for 62 days. Zebrafish fed a diet
      containing CHB-50 and CHB-62 accumulated newly formed CHB-40&41 and CHB-44,
      respectively. The biomagnifications factors (BMF) of the toxaphene congeners in
      Atlantic salmon muscle from the feeds spiked with technical toxaphene were
      significantly correlated with their relative lipophilicity (expressed as
      logK(ow)). An exception was CHB-44 which had a higher BMF than could be expected
      from its specific logK(ow), reflecting that CHB-44 is a metabolite formed under
      dietary exposure to CHB-62. This paper reports the in vivo dechlorination of nona
      chlorinated toxaphene congeners into octa-chlorinated congeners in feeding trials
      with a model fish (zebrafish) and an oily food fish (Atlantic salmon).

PMID- 22366426
TI  - Early stress responses in Atlantic salmon (Salmo salar) exposed to
      environmentally relevant concentrations of uranium.
AB  - Uranium (U) is a naturally occurring heavy metal widely used in many military and
      civil applications. Uranium contamination and the associated potential adverse
      effects of U on the aquatic environment have been debated during recent years. In
      order to understand the effect and mode of action (MoA) of U in vivo, juvenile
      Atlantic salmon (Salmo salar) were exposed to 0.25 mg/L, 0.5 mg/L and 1.0mg/L
      waterborne depleted uranyl acetate, respectively, in a static system for 48 h.
      The U concentrations in the gill and liver were analyzed by inductively coupled
      plasma mass spectrometry (ICP-MS) and the resulting biological effects were
      determined by a combination of analysis of gene expression and micronuclei
      formation. The hepatic transcriptional level of 12 biomarker genes from four
      stress-response categories, including oxidative stress (gamma-glutamyl cysteine
      synthetase (GCS), glutathione reductase (GR), glutathione peroxidase (GPx)), DNA
      damage and repair (P53, cyclin-dependent kinase inhibitor 1 (P21), growth arrest
      and DNA damage-inducible gene gamma (Gadd45G), proliferating cell nuclear antigen
      (PCNA), Rad51), apoptosis (Bcl2-associated X protein (BAX), Bcl-x, Caspase 6A,)
      and protein degradation (Ubiquitin) were evaluated by quantitative real-time
      polymerase chain reaction (q-rtPCR). The results clearly showed accumulation of U
      in the gill and liver with increasing concentrations of U in the exposure water.
      The effects of U on differential hepatic gene expression also occurred in a
      concentration-dependent manner, although deviations from ideal concentration
      response relationships were observed at the highest U concentration (1.0 mg/L).
      All the genes tested were found to be up-regulated by U while no significant
      micronuclei formation was identified. The results suggest that U may cause
      oxidative stress in fish liver at concentrations greater than 0.25 mg/L, giving
      rise to clear induction of several toxicologically relevant biomarker genes,
      although no significant adverse effects were observed after the relatively short
      exposure period.

PMID- 22366427
TI  - Self- and social perception of physical appearance in chest wall deformity.
AB  - This study analyzes self- and social perception of physical appearance in
      patients with chest wall deformity (CWD), including both pectus carinatum and
      pectus excavatum. Self-perception of appearance in 76 patients with CWD and
      social perception of patients' appearance by 20 adult and 20 adolescent raters
      was assessed using the Appearance Rating Scale (Stangier et al., 2000) and
      evaluated for agreement and multivariate correlates. Results indicate no
      agreement between self- and social rating. Based on mean scores patients rated
      their appearance significantly more negatively than adult raters but only
      slightly different than adolescent raters. Adolescent raters' judgment of the
      patients' appearance was related to CWD characteristics, while self-rating rather
      seems to be related to psychosocial factors. Because adolescents are a relevant
      peer group for adolescent patients with CWD their evaluation of the appearance
      might influence patients' self-image and might affect their psychological
      functioning. Effective interventions focusing on social interactions are needed.

PMID- 22366428
TI  - Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human
      cervical cancer cells in vitro.
AB  - Ganoderic acid T, a triterpenic acid produced by Ganoderma lucidum, has
      demonstrated therapeutic potential for tumor disease. In the current work,
      ganoderic acid T was modified to produce more effective small-molecule inhibitors
      of cancer cell proliferation. Moreover, the anticancer effects of three new
      ganoderic acid T derivatives, i.e., (22S,24E)-3alpha,15alpha,22-triacetoxy-5alpha
      lanosta-7,9(11),24-trien-26-oic acid ethyl ester (TLTO-Ee), (22S,24E)
      3alpha,15alpha,22-triacetoxy-5alpha-lanosta-7,9(11),24-trien-26-oic acid propyl
      ester (TLTO-Pe), and (22S,24E)-3alpha,15alpha,22-triacetoxy-5alpha-lanosta
      7,9(11),24-trien-26-oic acid amide (TLTO-A), and one known derivative, (22S,24E)
      3alpha,15alpha,22-triacetoxy-5alpha-lanosta-7,9(11),24-trien-26-oic acid methyl
      ester (TLTO-Me), on the cervical cell line HeLa were investigated and compared.
      MTT assay indicated that, among the tested compounds, TLTO-A displayed the
      highest inhibitory effect on the growth of HeLa cells, whereas it showed less
      cytotoxicity to the non-tumorous cell line MCF-10A than ganoderic acid T. Flow
      cytometry analysis revealed that all the compounds caused cell cycle arrest at
      the G1 phase and induced apoptosis. Furthermore, they decreased the mitochondrial
      membrane potential and enhanced the activities of pro-apoptotic factors caspase-3
      and caspase-9 in a dose-dependent manner. Accordingly, the apoptosis induction
      was presumed to occur through the endogenous pathway. The following order ranks
      both cytotoxic and pro-apoptotic effects of the compounds against HeLa cells:
      TLTO-A>ganoderic acid T~TLTO-Me~TLTO-Ee~TLTO-Pe. This study suggests that the
      carboxyl group of ganoderic acid T is not the main active group and is suitable
      for its further structural modification. The current work presents valuable
      information on the design of ganoderic acid T derivatives to develop potential
      chemotherapy agents.

PMID- 22366429
TI  - (-)Clausenamide facilitates synaptic transmission at hippocampal Schaffer
      collateral-CA1 synapses.
AB  - Clausenamide is a chiral compound isolated from leaves of the traditional Chinese
      herb Clausena lansium (lour) Skeels. It has been shown that (-)clausenamide, but
      not (+)clausenamide, improved learning and memory in amnesia animal models.
      However, the precise mechanism of clausenamide's actions remains unknown. Here we
      used an electrophysiological approach to observe the effect of (-)clausenamide on
      facilitating field excitatory postsynaptic potential (f-EPSP) in the CA1 area of
      hippocampal slices from rats. The results showed that (-)clausenamide enhanced
      synaptic transmission at doses 0.1, 1 and 10 MUM. The increase of f-EPSP induced
      by (-)clausenamide was completely inhibited by preincubation with nimodipine (L
      voltage-dependent calcium channel blocker, 10 MUM), but there was no change when
      nimodipine was added after (-)clausenamide application. However, ryanodine
      (ryanodine receptors blocker, 100 MUM) attenuated the slope of f-EPSP before or
      after (-)clausenamide incubation. The data suggested that (-)clausenamide
      promoted calcium influx to trigger intracellular calcium release which was
      responsible for potentiating synaptic transmission. Intracellular calcium release
      induced by (-)clausenamide promoted the activation of CaMKIIalpha at
      concentrations of 0.1, 1 and 10 MUM, and pretreatment with KN93 (CaMKIIalpha
      inhibitor, 10 MUM) completely blocked the enhancement of synaptic transmission
      induced by (-)clausenamide. cAMP response element-binding protein (CREB) was
      activated by (-)clausenamide and inhibited by KN93 preincubation, but H89 (PKA
      inhibitor, 10 MUM) had no effect, indicating that (-)clausenamide facilitated
      synaptic transmission by a PKA-independent pathway. Collectively, (-)clausenamide
      facilitated synaptic transmission by promoting calcium influx to trigger
      intracellular calcium release, subsequently activating CaMKIIalpha-CREB signal
      pathway.

PMID- 22366430
TI  - Galantamine (Reminyl) delays cardiac ventricular repolarization and prolongs the
      QT interval by blocking the HERG current.
AB  - Galantamine is a reversible inhibitor of acetylcholinesterase and an allosteric
      potentiating ligand of the nicotinic acetylcholine receptors. It is used for
      treating mild-to-moderate Alzheimer's disease. Interestingly, QT interval
      prolongation on the electrocardiogram (ECG), malignant ventricular arrhythmias
      and syncope have been reported with galantamine. Our objective was to evaluate
      the effects of galantamine on cardiac ventricular repolarization. Three sets of
      experiments were undertaken: 1) Whole cell patch-clamp experiments: HERG- or
      KCNQ1+KCNE1-transfected cells were exposed to galantamine 0.1-1000 MUmol/l (n=25
      cells, total) to assess drug effect on HERG and KCNQ1+KCNE1 currents. 2)
      Langendorff perfusion experiments: Isolated hearts from male Hartley guinea pigs
      (n=9) were exposed to galantamine 1 MUmol/l to assess drug-induced prolongation
      of monophasic action potential duration measured at 90% repolarization
      (MAPD(90)). 3) Cardiac telemetry experiments: Guinea pigs (n=7) implanted with
      wireless transmitters were injected a single intraperitoneal (i.p.) dose of
      galantamine 3mg/kg and 24h ECG recordings were made. 1) The estimated IC(50) for
      galantamine on HERG current was 760.2 MUmol/l. Moreover, galantamine 10 MUmol/l
      had a small inhibiting effect on KCNQ1+KCNE1 current (12.17 +/- 2.19% inhibition,
      n=10 cells). 2) While pacing at cycle lengths of 150, 200 or 250 ms, galantamine
      1 MUmol/l prolonged MAPD(90) by respectively 5.1 +/- 1.6 ms, 9.4 +/- 1.9 ms and
      12.1 +/- 2.1 ms. 3) Galantamine 3 mg/kgi.p. caused a maximal 11.9 +/- 2.7 ms
      prolongation of the corrected QT (QTc). Galantamine is a weak HERG blocker. This
      contributes to its mild QT-prolonging effect. Patients could be at risk of
      cardiac proarrhythmia during drug overdosage or interactions involving cytochrome
      2D6 drug-metabolizing enzyme.

PMID- 22366431
TI  - Knowledge and self-reported practice of the local inhabitants on traditional
      insect repellent plants in Western Hararghe zone, Ethiopia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper reveals the trend of knowledge and
      self-reported practice of traditional insect repellent plants (TIRPs) and could
      serve as a baseline data to identify/formulate novel plant-based insect
      repellents in the near future. AIM OF THE STUDY: Insect repellent plants usage is
      a long-standing and age old tradition. Thus, the major objective of this survey
      was to assess the knowledge and self-reported practice of the local inhabitants
      on TIRPs in Western Hararghe zone, Ethiopia. MATERIALS AND METHODS: The
      ethnobotanical survey was conducted between January and March 2011 via
      administering pre-tested questionnaire by involving the selected 150 household
      members in the study area. RESULTS: The survey results clearly reveal that nearly
      92.1% [90.1% (99/110) of female and 97.5% (39/40) of male] of the respondents
      have had adequate awareness on TIRPs. Leaves were the most widely applied plant
      parts and burning/smoldering the plant materials in order to generate smoke was
      the most common practice. Chi-square statistical analysis shows that there was no
      significant difference observed in the knowledge of the repellent plants between
      the gender (P-value=0.134), average monthly income (P-value=0.529) and
      educational status (P-value=0.107) but there was a significant association with
      the age (P-value=0.012) of respondents. However, repellent plants usage custom is
      significantly associated with gender (P-value=0.021) and educational status (P
      value=0.003) of the respondents but, there was such no significant relationship
      between the age (P-value=0.312) average monthly income (P-value=0.111) and
      repellent plants usage custom. CONCLUSION: Conducting more ethnobotanical survey
      on TIRPs is extremely important in order to generate and maintain the data-base.
      Besides, identifying the bio-active molecules, which are responsible for the
      repellent activity and eventually conducting laboratory and field based studies
      to evaluate their efficacy and safety are extremely imperative to formulate new
      classes of plant-based insect repellents/insecticides in the near future.

PMID- 22366432
TI  - Antidepressant-like effect of the ethanolic extract from Suanzaorenhehuan Formula
      in mice models of depression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaorenhehuan Formula (SHF) is a Chinese
      herbal formula for the treatment of depression-like disorders. It contains four
      herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen
      Platycladi. The present study is to investigate the antidepressant-like effect of
      the ethanolic extract of SHF and its possible mechanisms. MATERIALS AND METHODS:
      Mouse models of depression including the tail suspension test (TST), forced
      swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to
      evaluate the effects of SHF extract. The mechanisms were examined by measuring
      monoamine neurotransmitters in mice hippocampus and frontal cortex, testing
      monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice. RESULTS:
      After one-week treatment, SHF extract (50, 100 and 200mg/kg) induced a
      significant decrease on immobility time in TST. After two-week treatment, SHF
      extract (50, 100 and 200mg/kg) led to a reduction in the immobility period in TST
      and FST. The 5-HT levels in mice hippocampus were increased only after 200mg/kg
      SHF extract treatment. The noradrenaline (NE) levels were increased after
      200mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF
      extract (50, 100 and 200mg/kg) significantly inhibited monoamine oxidase-A (MAO
      A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure. CONCLUSION: These
      findings demonstrated that ethanolic SHF extract produced an antidepressant-like
      effect and the mechanism of action involves the serotonergic, noradrenergic and
      monoamine oxidase enzyme systems although underlying mechanism still remains to
      be further elucidated.

PMID- 22366434
TI  - Tong Luo Jiu Nao injection, a traditional Chinese medicinal preparation, inhibits
      MIP-1beta expression in brain microvascular endothelial cells injured by oxygen
      glucose deprivation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tong Luo Jiu Nao injection (TLJN), a modern
      Chinese formula based on Traditional Chinese Medicine theory, has been used to
      treat ischemic stroke and vascular dementia. TLJN belongs to the
      ethnopharmacological family of medicines. AIM OF THE STUDY: To investigate the
      protective effect of TLJN on oxygen-glucose deprivation (OGD) induced-injury of
      brain microvascular endothelial cells (BMECs). MATERIALS AND METHODS: The model
      of OGD was established in the primarily cultured BMECs. TLJN was added to the OGD
      injured BMECs for 6h. A series of assays were used to detect the effects of TLJN
      on: (i) MIP-1beta content in BMECs conditioned media (CM) by ELISA; (ii) MIP
      1beta protein expression in BMECs by western blotting and immunocytochemistry;
      (iii) the expression of CCR5, receptor of MIP-1beta, in BMECs by western
      blotting; (iv) the proliferative activity of microglial cells via the Cell
      Counting Kit-8 (CCK-8). RESULTS: Our results showed that the OGD-injured BMECs
      presented with large amounts of secretion and expression of MIP-1beta and up
      regulation of CCR5. Also, the CM of OGD-injured BMECs remarkably increased the
      proliferative activity of microglial cells. The TLJN-treated BMECs exhibited a
      reduction of MIP-1beta content in BMECs-CM and a down-regulation of MIP-1beta and
      CCR5 expression. In addition, an inhibitory effect of CM of OGD-injured plus TLJN
      injection-treated BMECs on microglial proliferation was also found. CONCLUSION:
      TLJN reduced the expression of MIP-1beta and CCR5 in OGD-injured BMECs, and the
      CM of OGD-injured plus TLJN injection-treated BMECs inhibited the proliferative
      activity of microglial cells, suggesting the therapeutic potential of TLJN on
      ischemic cerebral vascular disease.

PMID- 22366433
TI  - Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese
      herbal formula to promote diabetic wound healing.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) and Rehmanniae Radix (RR)
      are two traditional Chinese medicines widely used in China for treating diabetes
      mellitus and its complications, such as diabetic foot ulcer. AIM OF STUDY: In our
      previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was
      found effective in enhancing diabetic wound healing in rats through the actions
      of tissue regeneration, angiogenesis promotion and inflammation inhibition. The
      aims of the present study were to investigate the herb-herb interaction (or the
      possible synergistic effect) between AR and RR in NF3 to promote diabetic wound
      healing and to identify the principal herb in the formula by evaluating the
      potencies of individual AR and RR in different mechanistic studies. MATERIALS AND
      METHODS: A chemically induced diabetic foot ulcer rat model was used to examine
      the wound healing effect of NF3 and its individual herbs AR and RR. For
      mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human
      fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration
      assays were adopted to investigate the anti-inflammatory, granulation formation
      and angiogenesis-promoting activities of the herbal extracts, respectively.
      RESULTS: In the foot ulcer animal model, neither AR nor RR at clinical relevant
      dose (0.98g/kg) promoted diabetic wound healing. However, when they were used in
      combination as NF3, synergistic interaction was demonstrated, of which NF3 could
      significantly reduce the wound area of rats when compared to water group
      (p<0.01). For anti-inflammation and granulation formation, AR was more effective
      than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production
      from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect
      of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells.
      CONCLUSIONS: AR plays a preeminent role in the anti-inflammatory and fibroblast
      proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3
      to exert its overall wound-healing as well as the underlying angiogenesis
      promoting effects. The results of present study justified the combined usage of
      AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated
      that AR is the principal herb in this herbal formula.

PMID- 22366435
TI  - Inhibitory effects of Acorus calamus extracts on mast cell-dependent anaphylactic
      reactions using mast cell and mouse model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acorus calamus Linn. (Araceae) is a traditional
      herbal plant used for centuries to treat various allergic symptoms including
      asthma and bronchitis. AIM OF THE STUDY: The present study was focused to provide
      a pharmacological basis for the traditional use of Acorus calamus in allergic
      symptoms using the mast cell-dependent anaphylactic reactions in in vitro and in
      vivo models. MATERIALS AND METHODS: Cell viabilities were measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Dinitrophenyl
      human serum albumin (DNP-HSA) induced beta-hexosaminidase and interleukin (IL)-4
      productions in IgE-sensitized rat basophilic leukaemia (RBL-2H3) cells were
      measured by enzymatic assay and enzyme-linked immunosorbent assay (ELISA).
      Passive cutaneous anaphylaxis (PCA) reaction mouse model was implemented for in
      vivo studies. RESULTS: Hot water (HW), butylene glycol (BG), hexane (HE) and
      steam distilled (SD) extracts of Acorus calamus showed different cytoxicity
      levels evaluated in RBL-2H3 cells. Sub-toxic doses of HW extract suppressed the
      beta-hexosaminidase secretion and IL-4 production significantly and dose
      dependently in DNP-HSA induced IgE-sensitized RBL-2H3 cells compared to other
      extracts of Acorus calamus. Further, in vivo studies also revealed that the HW
      extract significantly inhibited the PCA reaction in mouse compared to the normal
      control group. CONCLUSION: HW extract of Acorus calamus most effectively
      inhibited degranulation and IL-4 secretion in DNP-HSA-stimulated RBL-2H3 cells
      and also reduced the mast cell-mediated PCA reaction in mouse, providing a
      therapeutic evidence for its traditional use in ameliorating allergic reactions.

PMID- 22366436
TI  - Back to basics: a revealing secondary reduction of the mitochondrial protein
      import pathway in diverse intracellular parasites.
AB  - Mitochondria are present in all eukaryotes, but remodeling of their metabolic
      contribution has in some cases left them almost unrecognizable and they are
      referred to as mitochondria-like organelles, hydrogenosomes or, in the case where
      evolution has led to a great deal of simplification, as mitosomes. Mitochondria
      rely on the import of proteins encoded in the nucleus and the protein import
      machinery has been investigated in detail in yeast: several sophisticated
      molecular machines act in concert to import substrate proteins across the outer
      mitochondrial membrane and deliver them to a precise sub-mitochondrial
      compartment. Because these machines are so sophisticated, it has been a major
      challenge to conceptualize the first phase of their evolution. Here we review
      recent studies on the protein import pathway in parasitic species that have
      mitosomes: in the course of their evolution for highly specialized niches these
      parasites, particularly Cryptosporidia and Microsporidia, have secondarily lost
      numerous protein functions, in accordance with the evolution of their genomes
      towards a minimal size. Microsporidia are related to fungi, Cryptosporidia are
      apicomplexans and kin to the malaria parasite Plasmodium; and this great
      phylogenetic distance makes it remarkable that Microsporidia and Cryptosporidia
      have independently evolved skeletal protein import pathways that are almost
      identical. We suggest that the skeletal pathway reflects the protein import
      machinery of the first eukaryotes, and defines the essential roles of the core
      elements of the mitochondrial protein import machinery. This article is part of a
      Special Issue entitled: Protein Import and Quality Control in Mitochondria and
      Plastids.

PMID- 22366437
TI  - Prognostic utility of angiogenesis and hypoxia effectors in patients with
      operable squamous cell cancer of the larynx.
AB  - Angiogenesis is active in localised laryngeal squamous cell carcinoma. We
      assessed relative messenger RNA (mRNA) and immunohistochemical (IHC) expression
      of Vascular Endothelial Growth Factors (VEGF) A, B, C, their receptors VEGFR1, 2,
      3, Neuropilins 1, 2 (NRP1, 2) and Hypoxia-Inducible Factor 1A (HIF1A) in paraffin
      embedded localised laryngeal carcinomas. In 289 patients with T3-4 (77.8%), node
      negative (84.1%) tumours of the larynx, high VEGFA and VEGFR1 mRNA correlated
      with advanced T stage, while low VEGFB and VEGFC mRNA with alcohol abuse and
      supraglottic primary, respectively (p<0.05). Age <55 was associated with high IHC
      expression of VEGFA, C and poor tumour differentiation with high IHC VEGFA. At a
      median follow-up of 74.5months, patients with VEGFR1-high tumours had
      significantly poorer disease-free survival (Hazard Ratio [HR] 1.93, p=0.008) and
      shorter overall survival (OS, HR 1.71, p=0.041). An association with dismal OS
      was seen for high VEGFR3 tumoural mRNA expression (HR 1.76, p=0.02). IHC
      expression of VEGF family proteins in the tumour was not prognostic and had poor
      concordance with mRNA expression (kappa<0.1, p=NS). In multivariate analysis,
      node-positive status, non-supraglottic localization, high VEGFR1 mRNA and high
      IHC VEGFA expression were significantly associated with relapse, while node
      positive status, high VEGFR1 and VEGFC mRNA expression in the tumour with risk of
      death. In laryngeal cancer, upregulated mRNA expression of VEGFR1 and VEGFC is
      associated with poor patient outcome.

PMID- 22366438
TI  - The role of IL-8 in the SDF-1alpha/CXCR4-induced angiogenesis of laryngeal and
      hypopharyngeal squamous cell carcinoma.
AB  - Stromal cell-derived factor-1 (SDF-1) (CXCL12) has been observed to promote
      laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) invasion through
      cooperation with its receptor CXCR4. Here, we further explore the angiogenesis
      mechanism induced by SDF-1/CXCR4 interaction in LHSCCs. Immunohistochemistry
      (IHC) reveals the significant correlation between CXCR4 and angiogenesis in
      tumors. After blocking the function of CXCR4 by specific inhibitor AMD3100 and
      neutralized antibody 12G5 or inhibiting the expression by siRNA, we were able to
      disrupt the HUVECs tube formation, demonstrating that SDF-1/CXCR4 indeed
      regulated the angiogenesis mechanism. The angiogenesis profiling from
      angiogenesis array and reverse transcription polymerase chain reaction indicates
      that IL-8 can be significantly triggered by SDF-1/CXCR4 interaction in LHSCCs. We
      also demonstrate that IL-8 secretion mechanism is regulated by Akt
      phosphorylation after SDF-1 stimulation. These results point out the importance
      of SDF-1/CXCR4 interaction in LHSCCs angiogenesis. The angiogenic factor IL-8
      would be triggered by the cooperation of SDF-1 and CXCR4 through an Akt-dependent
      pathway. This provides a new targeting therapy utility, disrupting SDF-1/CXCR4
      interaction combined with downstream-induced angiogenic factors in LHSCCs would
      be beneficial to improve clinical outcome.

PMID- 22366439
TI  - Can the transoral approach secure a cancer-free deep margin in tonsil cancer?
AB  - To verify whether the submuscular plane of the constrictor muscle, which is the
      resection margin in a transoral approach, is sufficient for securing a cancer
      free deep margin in tonsil cancer patients. Retrospective analysis of medical
      records and pathology specimens was done in sixty-two patients who were diagnosed
      with tonsil cancer and underwent surgery via a combined transoral-transcervical
      (transoral and transcervical lateral pharyngotomy) approach. The status of
      constrictor muscular invasion in tonsil cancer patients according to the TN stage
      and its predictors was investigated. Invasion or penetration of the constrictor
      muscle was found in three (27.3%), 30 (76.9%), and 12 (100%) stage T1, T2, and T3
      4 patients, respectively. In the univariate analysis, invasion or penetration of
      the constrictor muscle was significantly correlated with gender (p=0.004), stage
      >T2 (tumor >=2 cm; p=0.001), and N(+) (p=0.004). The multivariate analysis showed
      that stage >T2 [tumor >=2 cm; odds ratio (OR), 18.226; 95% confidence interval
      (CI), 2.976-111.608; p=0.002] and N(+) (OR, 7.560; 95% CI, 1.478-38.671; p=0.015)
      were significantly correlated with an increased risk of muscle invasion or
      penetration. The transoral approach is seems to be insufficient for securing a
      cancer-free deep margin in tonsil cancer beyond stage T2 or N1. The tumor beyond
      this stage should be treated more aggressively using multiple treatment
      modalities including radical surgery, chemotherapy, and radiotherapy.

PMID- 22366440
TI  - OrCa-dB: a complete catalogue of molecular and clinical information in oral
      carcinogenesis.

PMID- 22366441
TI  - Correlation of a priori DCE-MRI and (1)H-MRS data with molecular markers in neck
      nodal metastases: Initial analysis.
AB  - The aim of the present study is to correlate non-invasive, pretreatment
      biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic
      resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data
      in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC)
      patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal
      metastases of 12 patients who underwent surgery. Surgical specimens were analyzed
      with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular
      proliferation), vascular endothelial growth factor (VEGF) (the "endogenous
      marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible
      transcription factor (HIF-1alpha), and human papillomavirus (HPV). Additionally,
      necrosis was estimated based on H&E staining. The Spearman correlation was used
      to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant
      correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC
      expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki
      67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and
      rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not
      show significant correlation. The results of this preliminary study indicate that
      the level of heterogeneity of perfusion in metastatic HNSCC seems positively
      correlated with angiogenesis, and inversely correlated with proliferation. These
      results are preliminary in nature and are indicative, and not definitive, trends
      portrayed in HNSCC patients with nodal disease. Future studies with larger
      patient populations need to be carried out to validate and clarify our
      preliminary findings.

PMID- 22366442
TI  - Induction of lymphangiogenesis through vascular endothelial growth factor
      C/vascular endothelial growth factor receptor 3 axis and its correlation with
      lymph node metastasis in nasopharyngeal carcinoma.
AB  - The contribution of the lymphatic system to tumor metastasis is being
      increasingly appreciated through studies of human cancers. As the biological
      behavior of nasopharyngeal carcinoma (NPC) depends on its nodal status, patients
      with advanced nodal status show a higher tendency toward a poor outcome. Here, we
      examined the role of lymphangiogenesis on lymphatic spread of NPC. We also
      evaluated the involvement of vascular endothelial growth factor (VEGF)-C/VEGF
      receptor 3 (VEGFR3) signaling pathway on lymphangiogenesis in NPC. Furthermore,
      we tested whether Epstein-Barr virus (EBV)-latent membrane protein (LMP) 1
      induces VEGF-C. Forty-one patients with NPC were evaluated for expressions of
      VEGF-C and its receptor, VEGFR3, and LMP1 proteins and lymphatic vessel counts
      (LVC) highlighted by anti-podoplanin employing immunohistochemistry. The VEGF-C
      induction by LMP1 was then tested with Western blotting and enzyme-linked
      immunosorbent assay in vitro. The LVC and VEGF-C expression were significantly
      higher in cases with advanced regional lymph node metastasis (N2,3) than those
      with no or limited lymph node involvement (N0,1) (p=0.0380 and p=0.0109,
      respectively). In VEGF-C/VEGFR3-positive cases, the LVC were significantly
      increased compared with VEGF-C/VEGFR3-negative cases (p=0.0007). However, LMP1
      expression did not show significant associations with LVC and VEGF-C-expression
      scores (p=0.1210 and p=0.1324, respectively). Induction of VEGF-C protein by LMP1
      was not detected in vitro. These results suggest the involvement of the VEGF
      C/VEGFR3 axis in the induction of lymphangiogenesis which results in lymphatic
      spread of NPC. However, EBV-LMP1 was not associated with the mechanism.

PMID- 22366443
TI  - High stromal carbonic anhydrase IX expression is associated with nodal metastasis
      and decreased survival in patients with surgically-treated oral cavity squamous
      cell carcinoma.
AB  - Every year, approximately 25,000 patients are diagnosed with oral cavity squamous
      cell carcinoma (OCSCC) in the USA. The 5-year survival rate for OCSCC is
      approximately 40%. Intratumoral hypoxia confers poor prognosis and treatment
      failure but direct tumor oxygen measurement is challenging. Carbonic anhydrase IX
      (CAIX) is a marker of tissue hypoxia and we have recently shown that stromal CAIX
      is associated with reduced survival in patients with HPV-negative head and neck
      cancer. We examined the importance of this observation in OCSCC patients. We
      identified patients diagnosed and treated with OCSCC in Calgary (Alberta, Canada)
      between 1998 and 2005. Clinical and pathologic data were obtained from the
      Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were
      assembled from triplicate cores of archived tumor tissue. Stromal CAIX expression
      was assessed by quantitative immunohistochemistry (AQUA-HistoRx). The primary
      endpoint was disease-specific survival. We identified 102 patients with OCSCC; 87
      patients had surgery as their primary treatment and adequate tumor tissue for TMA
      construction was available for all patients. CAIX expression was evaluable for 61
      patients. High (top quartile) stromal CAIX expression was associated with
      significantly reduced 5-year disease-specific survival compared to low stromal
      CAIX expression (p<0.006). This study confirms our previously reported
      association between high stromal CAIX expression and significantly reduced
      overall survival in an independent, predominantly p16-negative, cohort of
      surgically treated OCSCC. Assessment of stromal CAIX expression could identify
      patients with the least favorable prognosis and inform therapeutic strategies in
      OCSCC.

PMID- 22366444
TI  - [Anterior pituitary failure secondary to intense exercise in a patient with
      Rathke's cleft cyst].

PMID- 22366445
TI  - [Corticotherapy: a useful update].

PMID- 22366446
TI  - A multisite randomized controlled effectiveness trial of cognitive processing
      therapy for military-related posttraumatic stress disorder.
AB  - Cognitive processing therapy (CPT) is currently applied in military veteran
      mental health services in many countries. This study tests the effectiveness of
      community-administered CPT for military-related PTSD under randomized controlled
      conditions. Fifty-nine treatment-seeking veterans with military-related PTSD were
      randomly allocated to receive 12 twice-weekly 60 min sessions of CPT or an
      equivalent period of usual treatment at veterans' community based counseling
      services. Intent to treat analyses found significantly greater improvement for
      participants receiving CPT over usual treatment at post-treatment and 3 month
      follow-up. CPT also produced greater improvements in anxiety, depression, social
      and dyadic relationships than usual treatment. No CPT related adverse events
      occurred during the trial. This trial reports the first randomized controlled
      trial evidence that CPT is an effective treatment for military PTSD and co-morbid
      conditions when compared to usual treatment and delivered in community settings
      by clinicians from diverse disciplines, preferred treatment orientation and
      levels of experience.

PMID- 22366447
TI  - Impulsive behaviors as an emotion regulation strategy: examining associations
      between PTSD, emotion dysregulation, and impulsive behaviors among substance
      dependent inpatients.
AB  - Recent investigations have demonstrated that posttraumatic stress disorder (PTSD)
      is associated with a range of impulsive behaviors (e.g., risky sexual behavior
      and antisocial behavior). The purpose of the present study was to extend extant
      research by exploring whether emotion dysregulation explains the association
      between PTSD and impulsive behaviors. Participants were an ethnically diverse
      sample of 206 substance use disorder (SUD) patients in residential substance
      abuse treatment. Results demonstrated an association between PTSD and impulsive
      behaviors, with SUD patients with PTSD reporting significantly more impulsive
      behaviors than SUD patients without PTSD (in general and when controlling for
      relevant covariates). Further, emotion dysregulation was found to fully mediate
      the relationship between PTSD and impulsive behaviors. Results highlight the
      relevance of emotion dysregulation to impulsive behaviors and suggest that
      treatments targeting emotion dysregulation may be useful in reducing impulsive
      behaviors among SUD patients with PTSD.

PMID- 22366448
TI  - Characteristics and anxiety symptom presentation associated with autism spectrum
      traits in youth with anxiety disorders.
AB  - There is limited information about the nature of anxiety among youth with
      symptoms of autism spectrum disorder (ASD). The present study examined (a)
      differences in the clinical characteristics of anxious youth with and without
      symptoms of ASD and (b) the symptoms of anxiety that best distinguish between
      these groups. Results indicated that anxious youth with elevated ASD symptoms had
      significantly more diagnoses (e.g., specific phobias), and were more likely to
      meet diagnostic criteria for social phobia (and list social concerns among their
      top fears) than youth without elevated ASD symptoms. At the symptom level,
      severity of interpersonal worry based on parent report and severity of fear of
      medical (doctor/dentist) visits based on youth report best differentiated ASD
      status. The findings inform diagnostic evaluations, case conceptualization, and
      treatment planning for youth with anxiety disorders and ASD symptoms.

PMID- 22366450
TI  - Cannabinoid receptors in submandibular acinar cells: functional coupling between
      saliva fluid and electrolytes secretion and Ca2+ signalling.
AB  - Cannabinoid receptors (CBRs) belong to the G protein-coupled receptor
      superfamily, and activation of CBRs in salivary cells inhibits agonist-stimulated
      salivation and modifies saliva content. However, the role of different CBR
      subtypes in acinar cell physiology and in intracellular signalling remains
      unclear. Here, we uncover functional CB(1)Rs and CB(2)Rs in acinar cells of rat
      submandibular gland and their essential role in saliva secretion. Pharmacological
      activation of CB(1)Rs and CB(2)Rs in the submandibular gland suppressed saliva
      outflow and modified saliva content produced by the submandibular gland in vivo.
      Using Na(+)-selective microelectrodes to record secretory Na(+) responses in the
      lumen of acini, we observed a reduction in Na(+) transport following the
      activation of CBRs, which was counteracted by the selective CB(1)R antagonist
      AM251. In addition, activation of CB(1)Rs or CB Rs caused inhibition of Na(+)
      K(+) 2 -ATPase activity in microsomes derived from the gland tissue as well as in
      isolated acinar cells. Using a Ca(2+) imaging technique, we showed that
      activation of CB(1)Rs and CB(2)Rs alters [Ca(2+)](cyt) signalling in acinar cells
      by distinct pathways, involving Ca(2+) release from the endoplasmic reticulum
      (ER) and store-operated Ca(2+) entry (SOCE), respectively. Our data demonstrate
      the expression of CB(1)Rs and CB(2)Rs in acinar cells, and their involvement in
      the regulation of salivary gland functioning.

PMID- 22366449
TI  - Inhibition of mRNA maturation in trypanosomes causes the formation of novel foci
      at the nuclear periphery containing cytoplasmic regulators of mRNA fate.
AB  - Maturation of all cytoplasmic mRNAs in trypanosomes involves trans-splicing of a
      short exon at the 5' end. Inhibition of trans-splicing results in an accumulation
      of partially processed oligocistronic mRNAs. Here, we show that the accumulation
      of newly synthesised partially processed mRNAs results in the formation of foci
      around the periphery of the nucleus. These nuclear periphery granules (NPGs)
      contain the full complement of P-body proteins identified in trypanosomes to
      date, as well as poly(A)-binding protein 2 and the trypanosome homologue of the
      RNA helicase VASA. NPGs resemble perinuclear germ granules from metazoa more than
      P-bodies because they: (1) are localised around the nuclear periphery; (2) are
      dependent on active transcription; (3) are not dissipated by cycloheximide; (4)
      contain VASA; and (5) depend on nuclear integrity. In addition, NPGs can be
      induced in cells depleted of the P-body core component SCD6. The description of
      NPGs in trypanosomes provides evidence that there is a perinuclear compartment
      that can determine the fate of newly transcribed mRNAs and that germ granules
      could be a specialised derivative.

PMID- 22366451
TI  - Met receptor tyrosine kinase signals through a cortactin-Gab1 scaffold complex,
      to mediate invadopodia.
AB  - Invasive carcinoma cells form actin-rich matrix-degrading protrusions called
      invadopodia. These structures resemble podosomes produced by some normal cells
      and play a crucial role in extracellular matrix remodeling. In cancer, formation
      of invadopodia is strongly associated with invasive potential. Although
      deregulated signals from the receptor tyrosine kinase Met (also known as
      hepatocyte growth factor are linked to cancer metastasis and poor prognosis, its
      role in invadopodia formation is not known. Here we show that stimulation of
      breast cancer cells with the ligand for Met, hepatocyte growth factor, promotes
      invadopodia formation, and in aggressive gastric tumor cells where Met is
      amplified, invadopodia formation is dependent on Met activity. Using both GRB2
      associated-binding protein 1 (Gab1)-null fibroblasts and specific knockdown of
      Gab1 in tumor cells we show that Met-mediated invadopodia formation and cell
      invasion requires the scaffold protein Gab1. By a structure-function approach, we
      demonstrate that two proline-rich motifs (P4/5) within Gab1 are essential for
      invadopodia formation. We identify the actin regulatory protein, cortactin, as a
      direct interaction partner for Gab1 and show that a Gab1-cortactin interaction is
      dependent on the SH3 domain of cortactin and the integrity of the P4/5 region of
      Gab1. Both cortactin and Gab1 localize to invadopodia rosettes in Met-transformed
      cells and the specific uncoupling of cortactin from Gab1 abrogates invadopodia
      biogenesis and cell invasion downstream from the Met receptor tyrosine kinase.
      Met localizes to invadopodia along with cortactin and promotes phosphorylation of
      cortactin. These findings provide insights into the molecular mechanisms of
      invadopodia formation and identify Gab1 as a scaffold protein involved in this
      process.

PMID- 22366453
TI  - Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in
      differentiating male germ cells.
AB  - CIZ1 is a nuclear-matrix-associated DNA replication factor unique to higher
      eukaryotes, for which alternatively spliced isoforms have been associated with a
      range of disorders. In vitro, the CIZ1 N-terminus interacts with cyclin E and
      cyclin A at distinct sites, enabling functional cooperation with cyclin-A-Cdk2 to
      promote replication initiation. C-terminal sequences anchor CIZ1 to fixed sites
      on the nuclear matrix, imposing spatial constraint on cyclin-dependent kinase
      activity. Here we demonstrate that CIZ1 is predominantly expressed as a predicted
      full-length product throughout mouse development, consistent with a ubiquitous
      role in cell and tissue renewal. CIZ1 is expressed in proliferating stem cells of
      the testis, but is notably downregulated following commitment to differentiation.
      Significantly, CIZ1 is re-expressed at high levels in non-proliferative
      spermatocytes before meiotic division. Sequence analysis identifies at least
      seven alternatively spliced variants, including a dominant cancer-associated form
      and a set of novel isoforms. Furthermore, we show that in these post-replicative
      cells, CIZ1 interacts with germ-cell-specific cyclin A1, which has been
      implicated in the repair of DNA double-strand breaks. Consistent with this role,
      antibody depletion of CIZ1 reduces the capacity for testis extract to repair
      digested plasmid DNA in vitro. Together, the data imply post-replicative roles
      for CIZ1 in germ cell differentiation that might include meiotic recombination -
      a process intrinsic to genome stability and diversification.

PMID- 22366452
TI  - Sculpting the endomembrane system in deep time: high resolution phylogenetics of
      Rab GTPases.
AB  - The presence of a nucleus and other membrane-bounded intracellular compartments
      is the defining feature of eukaryotic cells. Endosymbiosis accounts for the
      origins of mitochondria and plastids, but the evolutionary ancestry of the
      remaining cellular compartments is incompletely documented. Resolving the
      evolutionary history of organelle-identity encoding proteins within the
      endomembrane system is a necessity for unravelling the origins and
      diversification of the endogenously derived organelles. Comparative genomics
      reveals events after the last eukaryotic common ancestor (LECA), but resolution
      of events prior to LECA, and a full account of the intracellular compartments
      present in LECA, has proved elusive. We have devised and exploited a new
      phylogenetic strategy to reconstruct the history of the Rab GTPases, a key family
      of endomembrane-specificity proteins. Strikingly, we infer a remarkably
      sophisticated organellar composition for LECA, which we predict possessed as many
      as 23 Rab GTPases. This repertoire is significantly greater than that present in
      many modern organisms and unexpectedly indicates a major role for secondary loss
      in the evolutionary diversification of the endomembrane system. We have
      identified two Rab paralogues of unknown function but wide distribution, and thus
      presumably ancient nature; RabTitan and RTW. Furthermore, we show that many Rab
      paralogues emerged relatively suddenly during early metazoan evolution, which is
      in stark contrast to the lack of significant Rab family expansions at the onset
      of most other major eukaryotic groups. Finally, we reconstruct higher-order
      ancestral clades of Rabs primarily linked with endocytic and exocytic process,
      suggesting the presence of primordial Rabs associated with the establishment of
      those pathways and giving the deepest glimpse to date into pre-LECA history of
      the endomembrane system.

PMID- 22366454
TI  - CDK regulates septin organization through cell-cycle-dependent phosphorylation of
      the Nim1-related kinase Gin4.
AB  - Cyclin-dependent kinases (CDKs) regulate septin organization in a cell-cycle
      dependent manner in yeast. However, the mechanism remains unclear. Here, we show
      that the Candida albicans CDK Cdc28 phosphorylates the Nim1-related kinase Gin4,
      a known septin regulator, activating its kinase activity, which in turn
      phosphorylates the Sep7 septin. Gin4 contains a cluster of CDK phosphorylation
      sites near the kinase domain. Replacing serine/threonine with alanine in these
      sites prevents Gin4 activation, weakens its association with Sep7, alters Sep7
      dynamics and causes morphological and cytokinetic defects. By contrast,
      phosphomimetic mutation enhances the kinase activity with only moderate
      deteriorating effects. We also found that Gin4 has both kinase-independent and 
      dependent functions, acting during G1 phase and mitosis, respectively, with the
      former being essential for septin ring assembly. Thus, we have identified a
      previously unknown signaling pathway linking CDKs and the septins that provides
      new insights into the mechanisms controlling septin organization and function in
      coordination with cell-cycle phases.

PMID- 22366455
TI  - Increased retinoic acid levels through ablation of Cyp26b1 determine the
      processes of embryonic skin barrier formation and peridermal development.
AB  - The process by which the periderm transitions to stratified epidermis with the
      establishment of the skin barrier is unknown. Understanding the cellular and
      molecular processes involved is crucial for the treatment of human pathologies,
      where abnormal skin development and barrier dysfunction are associated with
      hypothermia and perinatal dehydration. For the first time, we demonstrate that
      retinoic acid (RA) levels are important for periderm desquamation, embryonic skin
      differentiation and barrier formation. Although excess exogenous RA has been
      known to have teratogenic effects, little is known about the consequences of
      elevated endogenous retinoids in skin during embryogenesis. Absence of cytochrome
      P450, family 26, subfamily b, polypeptide 1 (Cyp26b1), a retinoic-acid-degrading
      enzyme, results in aberrant epidermal differentiation and filaggrin expression,
      defective cornified envelopes and skin barrier formation, in conjunction with
      peridermal retention. We show that these alterations are RA dependent because
      administration of exogenous RA in vivo and to organotypic skin cultures phenocopy
      Cyp26b1(-/-) skin abnormalities. Furthermore, utilizing the Flaky tail (Ft/Ft)
      mice, a mouse model for human ichthyosis, characterized by mutations in the
      filaggrin gene, we establish that proper differentiation and barrier formation is
      a prerequisite for periderm sloughing. These results are important in
      understanding pathologies associated with abnormal embryonic skin development and
      barrier dysfunction.

PMID- 22366456
TI  - Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal
      muscle stem cells.
AB  - Skeletal muscle stem cell fate in adult mice is regulated by crucial
      transcription factors, including the determination genes Myf5 and Myod. The
      precise role of Myf5 in regulating quiescent muscle stem cells has remained
      elusive. Here we show that most, but not all, quiescent satellite cells express
      Myf5 protein, but at varying levels, and that resident Myf5 heterozygous muscle
      stem cells are more primed for myogenic commitment compared with wild-type
      satellite cells. Paradoxically however, heterotypic transplantation of Myf5
      heterozygous cells into regenerating muscles results in higher self-renewal
      capacity compared with wild-type stem cells, whereas myofibre regenerative
      capacity is not altered. By contrast, Pax7 haploinsufficiency does not show major
      modifications by transcriptome analysis. These observations provide a mechanism
      linking Myf5 levels to muscle stem cell heterogeneity and fate by exposing two
      distinct and opposing phenotypes associated with Myf5 haploinsufficiency. These
      findings have important implications for how stem cell fates can be modulated by
      crucial transcription factors while generating a pool of responsive heterogeneous
      cells.

PMID- 22366457
TI  - The Rac GEF ZizB regulates development, cell motility and cytokinesis in
      Dictyostelium.
AB  - Dock (dedicator of cytokinesis) proteins represent a family of guanine nucleotide
      exchange factors (GEFs) that include the well-studied Dock180 family and the
      poorly characterised zizimin family. Our current understanding of Dock180
      function is that it regulates Rho small GTPases and thus has a role in a number
      of cell processes, including cell migration, development and division. Here, we
      use a tractable model for cell motility research, Dictyostelium discoideum, to
      help elucidate the role of the related zizimin proteins. We show that gene
      ablation of zizA causes no change in development, whereas ablation of zizB gives
      rise to an aberrant developmental morphology and a reduction in cell
      directionality and velocity, and altered cell shape. Fluorescently labelled ZizA
      protein associates with the microtubule-organising centre (MTOC), whereas ZizB is
      enriched in the cortex. Overexpression of ZizB also causes an increase in the
      number of filopodia and a partial inhibition of cytokinesis. Analysis of ZizB
      protein binding partners shows that it interacts with Rac1a and a range of actin
      associated proteins. In conclusion, our work provides insight into the molecular
      and cellular functions of zizimin GEF proteins, which are shown to have a role in
      cell movement, filopodia formation and cytokinesis.

PMID- 22366458
TI  - Nuclear import of hTERT requires a bipartite nuclear localization signal and Akt
      mediated phosphorylation.
AB  - Sustained cell proliferation requires telomerase to maintain functional telomeres
      that are essential for chromosome integrity and protection. Although nuclear
      import of telomerase transcriptase (hTERT) is required for telomerase activity to
      elongate telomeres in vivo, the molecular mechanism regulating nuclear
      localization of hTERT is unclear. We have identified a bipartite nuclear
      localization signal (NLS; amino acid residues 222-240) that is responsible for
      nuclear import of hTERT. Immunofluorescence imaging of hTERT revealed that
      mutations in any of the bipartite NLS sequences result in decreased nuclear
      fluorescence intensity compared with wild-type hTERT. We also show that Akt
      mediated phosphorylation at serine 227 is necessary for directing nuclear
      translocation of hTERT. Interestingly, serine 227 is located between two clusters
      of basic amino acids in the bipartite NLS. Inactivation of Akt activity by a
      dominant-negative mutant or wortmannin treatment attenuated nuclear localization
      of hTERT. We further show that both bipartite NLS and serine 227 in hTERT are
      required for cell immortalization of normal human foreskin fibroblast cells.
      Taken together, our findings reveal a previously unknown regulatory mechanism for
      nuclear import of hTERT through a bipartite NLS mediated by Akt phosphorylation,
      which represents an alternative pathway for modulating telomerase activity in
      cancer.

PMID- 22366459
TI  - Re-replication induced by geminin depletion occurs from G2 and is enhanced by
      checkpoint activation.
AB  - To prevent re-replication of DNA in a single cell cycle, the licensing of
      replication origins by Mcm2-7 is prevented during S and G2 phases. Animal cells
      achieve this by cell-cycle-regulated proteolysis of the essential licensing
      factor Cdt1 and inhibition of Cdt1 by geminin. Here we investigate the
      consequences of ablating geminin in synchronised human U2OS cells. Following
      geminin loss, cells complete an apparently normal S phase, but a proportion
      arrest at the G2-M boundary. When Cdt1 accumulates in these cells, DNA re
      replicates, suggesting that the key role of geminin is to prevent re-licensing in
      G2. If cell cycle checkpoints are inhibited in cells lacking geminin, cells
      progress through mitosis and less re-replication occurs. Checkpoint kinases
      thereby amplify re-replication into an all-or-nothing response by delaying
      geminin-depleted cells in G2. Deep DNA sequencing revealed no preferential re
      replication of specific genomic regions after geminin depletion. This is
      consistent with the observation that cells in G2 have lost their replication
      timing information. By contrast, when Cdt1 is overexpressed or is stabilised by
      the neddylation inhibitor MLN4924, re-replication can occur throughout S phase.

PMID- 22366460
TI  - Nuclear inheritance and genetic exchange without meiosis in the binucleate
      parasite Giardia intestinalis.
AB  - The protozoan parasite Giardia intestinalis (also known as Giardia lamblia) is a
      major waterborne pathogen. During its life cycle, Giardia alternates between the
      actively growing trophozoite, which has two diploid nuclei with low levels of
      allelic heterozygosity, and the infectious cyst, which has four nuclei and a
      tough outer wall. Although the formation of the cyst wall has been studied
      extensively, we still lack basic knowledge about many fundamental aspects of the
      cyst, including the sources of the four nuclei and their distribution during the
      transformation from cyst into trophozoite. In this study, we tracked the
      identities of the nuclei in the trophozoite and cyst using integrated nuclear
      markers and immunofluorescence staining. We demonstrate that the cyst is formed
      from a single trophozoite by a mitotic division without cytokinesis and not by
      the fusion of two trophozoites. During excystation, the cell completes
      cytokinesis to form two daughter trophozoites. The non-identical nuclear pairs
      derived from the parent trophozoite remain associated in the cyst and are
      distributed to daughter cells during excystation as pairs. Thus, nuclear sorting
      (such that each daughter cell receives a pair of identical nuclei) does not
      appear to be a mechanism by which Giardia reduces heterozygosity between its
      nuclei. Rather, we show that the cyst nuclei exchange chromosomal genetic
      material, perhaps as a way to reduce heterozygosity in the absence of meiosis and
      sex, which have not been described in Giardia. These results shed light on
      fundamental aspects of the Giardia life cycle and have implications for our
      understanding of the population genetics and cell biology of this binucleate
      parasite.

PMID- 22366461
TI  - Brc1-dependent recovery from replication stress.
AB  - BRCT-containing protein 1 (Brc1) is a multi-BRCT (BRCA1 carboxyl terminus) domain
      protein in Schizosaccharomyces pombe that is required for resistance to chronic
      replicative stress, but whether this reflects a repair or replication defect is
      unknown and the subject of this study. We show that brc1Delta cells are
      significantly delayed in recovery from replication pausing, though this does not
      activate a DNA damage checkpoint. DNA repair and recombination protein Rad52 is a
      homologous recombination protein that loads the Rad51 recombinase at resected
      double-stranded DNA (dsDNA) breaks and is also recruited to stalled replication
      forks, where it may stabilize structures through its strand annealing activity.
      Rad52 is required for the viability of brc1Delta cells, and brc1Delta cells
      accumulate Rad52 foci late in S phase that are potentiated by replication stress.
      However, these foci contain the single-stranded DNA (ssDNA) binding protein RPA,
      but not Rad51 or gammaH2A. Further, these foci are not associated with increased
      recombination between repeated sequences, or increased post-replication repair.
      Thus, these Rad52 foci do not represent sites of recombination. Following the
      initiation of DNA replication, the induction of these foci by replication stress
      is suppressed by defects in origin recognition complex (ORC) function, which is
      accompanied by loss of viability and severe mitotic defects. This suggests that
      cells lacking Brc1 undergo an ORC-dependent rescue of replication stress,
      presumably through the firing of dormant origins, and this generates RPA-coated
      ssDNA and recruits Rad52. However, as Rad51 is not recruited, and the checkpoint
      effector kinase Chk1 is not activated, these structures must not contain the
      unprotected primer ends found at sites of DNA damage that are required for
      recombination and checkpoint activation.

PMID- 22366462
TI  - RhoB regulates uPAR signalling.
AB  - Urokinase-type plasminogen activator (uPA) and its receptor, uPAR, play important
      roles in promoting cancer cell adhesion, migration and invasion. Rho GTPases are
      key coordinators of these processes; the Rho GTPase Rac1 has previously been
      implicated in uPA- and/or uPAR-induced migratory or morphological cell responses.
      We used RNAi to deplete 12 different Rho GTPases to screen for effects on uPA
      stimulated migration, and found that depletion of RhoB significantly reduces uPA
      induced migration and invasion of prostate carcinoma cells. RhoB depletion did
      not affect the expression or surface levels of uPAR but reduced the uPAR-induced
      increase in levels of several integrins and inhibited uPAR signalling to the
      actin regulator cofilin, the cell-adhesion signal-transduction adaptor molecule
      paxillin and the serine/threonine kinase Akt. uPAR rapidly activated RhoB and
      increased RhoB expression. RhoB depletion also reduced cell adhesion to and
      spreading on vitronectin, which is a uPAR ligand. This correlated with decreased
      association between integrins and uPAR and reduced integrin beta1 activity. Our
      results indicate that RhoB is a key regulator of uPAR signalling in cell
      adhesion, migration and invasion.

PMID- 22366463
TI  - A method for the specific detection of resident bacteria in brine shrimp larvae.
AB  - In this study, we describe an easy but efficient method to specifically target
      the intestinal resident microbiota in brine shrimp larvae during DGGE analysis,
      hereby excluding the interference of both transient (luminal) bacteria and body
      surface bacteria. This effective technique has several advantages over
      alternative methods, with respect of ease of use and rapidity.

PMID- 22366464
TI  - Minimum taxonomic criteria for bacterial genome sequence depositions and
      announcements.
AB  - Multiple bioinformatic methods are available to analyse the information encoded
      within the complete genome sequence of a bacterium and accurately assign its
      species status or nearest phylogenetic neighbour. However, it is clear that even
      now in what is the third decade of bacterial genomics, taxonomically incorrect
      genome sequence depositions are still being made. We outline a simple scheme of
      bioinformatic analysis and a set of minimum criteria that should be applied to
      all bacterial genomic data to ensure that they are accurately assigned to the
      species or genus level prior to database deposition. To illustrate the utility of
      the bioinformatic workflow, we analysed the recently deposited genome sequence of
      Lactobacillus acidophilus 30SC and demonstrated that this DNA was in fact derived
      from a strain of Lactobacillus amylovorus. Using these methods researchers can
      ensure that the taxonomic accuracy of genome sequence depositions is maintained
      within the ever increasing nucleic acid datasets.

PMID- 22366465
TI  - Expression of multi-drug resistance-related genes MDR3 and MRP as prognostic
      factors in clinical liver cancer patients.
AB  - BACKGROUND/AIMS: To investigate the expression of multi-drug resistance-related
      genes, MDR3 and MRP, in clinical specimens of primary liver cancer and their
      potential as prognostic factors in liver cancer patients. METHODOLOGY: A total of
      26 patients with primary liver cancer were enrolled. The expression of MDR3 and
      MRP genes was measured by real-time PCR and the association between gene
      expression and the prognosis of patients was analyzed by the Kaplan-Meier method
      and COX regression model. RESULTS: This study showed that increases in MDR3 gene
      expression were identified in cholangiocellular carcinoma, cirrhosis and HBsAg
      positive patients, while MRP expression increased in hepatocellular carcinoma,
      non-cirrhosis and HBsAg-negative patients. Moreover, conjugated bilirubin and
      total bile acid in the serum were significantly reduced in patients with high MRP
      expression compared to patients with low expression. The overall survival tended
      to be longer in patients with high MDR3 and MRP expression compared to the
      control group. MRP might be an independent prognostic factor in patients with
      liver cancer by COX regression analysis. CONCLUSIONS: MDR3 and MRP may play
      important roles in liver cancer patients as prognostic factors and their
      underlying mechanisms in liver cancer are worthy of further investigation.

PMID- 22366466
TI  - The impact of hepatic denervation on the accumulation of hepatic progenitor cells
      during liver regeneration in rats.
AB  - BACKGROUND/AIMS: All autonomic hepatic nerves are transected following liver
      transplantation. Recent studies have shown the relationship between an inhibition
      of autonomic nerves and the accumulation of hepatic progenitor cells (HPC). This
      study aims to elucidate the influence of hepatic denervation on the accumulation
      of HPC in the process of liver regeneration. METHODOLOGY: Male Sprague-Dawley
      rats underwent hepatic denervation. Immediately after either denervation (DN
      group, n=30) or a sham operation (control group, n=30), a two-thirds hepatectomy
      was performed, and these were sacrificed chronologically. An immunohistochemical
      analysis of HPC was performed with a mouse monoclonal OV6 type antibody. RESULTS:
      The liver per body weight ratio gradually increased in both groups. On
      postoperative day (POD) 7, the DN group showed a significantly higher ratio. The
      HPC expression gradually increased in both groups. The maximal HPC number was
      observed on POD 7 in the DN group and on POD 3 in the control group. Although
      there was no significant difference in the HPC numbers between the DN and control
      group until POD 3, the number of HPC were significantly higher in livers of the
      denervated rats than in those of the sham operated rats between POD 5 and 14.
      CONCLUSIONS: The hepatic autonomic nerves were thus suggested to play an
      important role in the accumulation of HPC during liver regeneration in rats.

PMID- 22366467
TI  - Surgical treatment of retrorectal tumors: a retrospective study of a ten-year
      experience in three institutions.
AB  - BACKGROUND/AIMS: The relative rarity and anatomical position of retrorectal
      tumors may lead to difficulty in diagnosis and surgical management. METHODOLOGY:
      This was a retrospective review of 93 patients who had resection of retrorectal
      tumors between 2002 and 2011. RESULTS: All patients in this study were treated
      with excision of the retrorectal tumors. Surgical approach included transsacral
      approach (78 cases), transabdominal approach (12 cases) and combined approach (3
      cases). Seventy-two benign lesions (77.4%) and 21 malignant (22.6%) were
      confirmed by histological examination. The 72 benign cases included dermoid cysts
      (26 cases), simple cysts (12 cases), teratomas (12 cases), neurofibromas (12
      cases), fibrolipomas (6 cases), neurilemmomas (3 cases) and synovioma (1 case).
      The twenty-one malignant cases included lymphomas (6 cases), malignant teratomas
      (5 cases), fibrosarcomas (3 cases), interstitialomas (6 cases) and malignant
      mesothelioma (1 case). Complications occurred in 16.1% of patients including
      intra-operative bleedings (6 cases), rectal injury (6 cases) and presacral
      infection (3 cases). CONCLUSIONS: Primary retrorectal tumors are very rare.
      Successful treatment of these tumors requires extensive knowledge of pelvic
      anatomy and expertise in pelvic surgery.

PMID- 22366468
TI  - Promiscuity comes at a price: catalytic versatility vs efficiency in different
      metal ion derivatives of the potential bioremediator GpdQ.
AB  - The glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) is a highly
      promiscuous dinuclear metallohydrolase with respect to both substrate specificity
      and metal ion composition. While this promiscuity may adversely affect the
      enzyme's catalytic efficiency its ability to hydrolyse some organophosphates
      (OPs) and by-products of OP degradation have turned GpdQ into a promising
      candidate for bioremedial applications. Here, we investigated both metal ion
      binding and the effect of the metal ion composition on catalysis. The prevalent
      in vivo metal ion composition for GpdQ is proposed to be of the type
      Fe(II)Zn(II), a reflection of natural abundance rather than catalytic
      optimisation. The Fe(II) appears to have lower binding affinity than other
      divalent metal ions, and the catalytic efficiency of this mixed metal center is
      considerably smaller than that of Mn(II), Co(II) or Cd(II)-containing derivatives
      of GpdQ. Interestingly, metal ion replacements do not only affect catalytic
      efficiency but also the optimal pH range for the reaction, suggesting that
      different metal ion combinations may employ different mechanistic strategies.
      These metal ion-triggered modulations are likely to be mediated via an extensive
      hydrogen bond network that links the two metal ion binding sites via residues in
      the substrate binding pocket. The observed functional diversity may be the cause
      for the modest catalytic efficiency of wild-type GpdQ but may also be essential
      to enable the enzyme to evolve rapidly to alter substrate specificity and enhance
      k(cat) values, as has recently been demonstrated in a directed evolution
      experiment. This article is part of a Special Issue entitled: Chemistry and
      mechanism of phosphatases, diesterases and triesterases.

PMID- 22366469
TI  - AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct
      metastatic potential.
AB  - BACKGROUND: Despite recent advances, it is not clear to correlate the mechanical
      compliances and the metastatic potential of cancer cells. In this study, we
      investigated combined signatures of mechanical compliances, adhesions, and
      calcium dynamics correlated with the metastatic potential of cancer cells. SCOPE
      OF REVIEW: We used the lowly (LNCaP) and highly (CL-1, CL-2) metastatic human
      prostate cancer cells. The AFM-based nanomechanics was performed to determine the
      elastic moduli and the cell-to-substrate adhesion. The intracellular calcium
      dynamics was evaluated by fluorescence spectroscopy. Cell migration and the
      distribution of cytoskeleton were evaluated using the wounded monolayer model and
      immunofluorescence, respectively. The elastic moduli, the calcium dynamics, and
      the migratory ability are greater in CL-1 and CL-2 than LNCaP. CL-1 and CL-2 also
      display a significantly larger area of cell-to-substrate adhesions while the
      LNCaP displays a limited adhesion. These properties were slightly reduced in CL-2
      compared with CL-1 cells. The enhanced elastic moduli and calcium dynamics found
      in CL-1 and CL-2 can be consistently explained by the intensified tensile stress
      generated by actin cytoskeletons anchored at more focal adhesion sites. MAJOR
      CONCLUSIONS: Although the suppressed mechanical compliance of highly metastatic
      cells may not support the enhanced cancer metastasis, the enhanced adhesion and
      calcium dynamics are favorable for invasion and extra-vasation required for
      malignant progression. GENERAL SIGNIFICANCE: Our results suggest that the
      mechanical compliance alone may fail to indicate the metastatic progression, but
      the combined biomechanical signatures of mechanical compliance, adhesion, and
      calcium dynamics can provide critical clues to determine the metastatic potential
      of cells.

PMID- 22366470
TI  - Pre- and postprandial changes in orexigenic and anorexigenic factors in channel
      catfish (Ictalurus punctatus).
AB  - Ghrelin (GRLN), cocaine and amphetamine regulated transcript (CART), neuropeptide
      Y (NPY), and cholecystokinin (CCK) are neuropeptides involved in the regulation
      of appetite and feeding in vertebrates. We examined pre- and postprandial changes
      in the expression of plasma GHRL and mRNAs encoding GRLN, CART, NPY, and CCK in
      channel catfish. Fish were entrained to eat at 0900 h for 2 weeks. Fish were then
      sampled at 0700, 0800, and 0900 h. Remaining fish were either offered feed at
      0900 h (Fed) or fasted (Unfed). Fish sampling continued at 0.5, 1, 2, and 4 h
      post feeding. Feeding increased abundance of whole brain CART mRNA out to 4 h
      with no effect observed in unfed fish. Whole brain NPY expression peaked at 0.5 h
      in both treatments. NPY expression then declined in fed fish but remained
      elevated in unfed fish. No differences in plasma or stomach GRLN expression were
      observed. Two separate cDNAs for CCK were identified. Brain CCKa and CCKb
      expression increased after feeding. These results suggest CART, NPY, and CCK play
      roles in the regulation of channel catfish feeding. Taken together, these results
      provide new insights into the neural and gastroenteric mechanisms regulating
      appetite in channel catfish.

PMID- 22366471
TI  - Regulatory role of kit ligand-c-kit interaction and oocyte factors in
      steroidogenesis by rat granulosa cells.
AB  - Although kit ligand (KL)-c-kit interaction is known to be critical for oogenesis
      and folliculogenesis, its role in ovarian steroidogenesis has yet to be
      elucidated. We studied the impact of KL-c-kit interaction in regulation of
      steroidogenesis using rat oocyte/granulosa cell co-culture. In the presence of
      oocytes, soluble KL suppressed FSH-induced estradiol production and aromatase
      mRNA expression without affecting FSH-induced progesterone production. The KL
      effect on steroidogenesis was interrupted by an anti-c-kit neutralizing antibody,
      suggesting that KL-c-kit interaction is involved in suppression of estrogen by
      granulosa cells through oocyte c-kit action. The cAMP-PKA pathway activity was
      not directly involved in the estrogen regulation by KL-c-kit action. It was of
      note that KL treatment increased the expression levels of oocyte-derived FGF-8,
      GDF-9 and BMP-6, while it reduced the expression levels of oocyte-derived BMP-15
      in the oocyte-granulosa cell co-culture. Given the findings that FGF-8, but not
      GDF-9, BMP-6 or -15, suppressed FSH-induced estrogen production by granulosa
      cells, oocyte-derived FGF-8 is linked to suppression of FSH-induced estrogen
      production through the KL-c-kit interaction. Furthermore, the suppression of FSH
      induced estrogen production by KL in the co-culture was reversed by a FGF
      receptor kinase inhibitor and the effect of the inhibitor was enhanced in
      combination with extracellular-domain protein of BMPRII, which interferes with
      BMP-15 and GDF-9 activities. Thus, the actions of endogenous oocyte factors
      including FGF-8 and BMP-15/GDF-9 were involved in the KL activity that inhibited
      FSH-induced estradiol production. Collectively, the results indicate that KL-c
      kit interaction plays a role in estrogenic regulation through oocyte-granulosa
      cell communication.

PMID- 22366472
TI  - The C-terminal domains of melanocortin-2 receptor (MC2R) accessory proteins
      (MRAP1) influence their localization and ACTH-induced cAMP production.
AB  - ACTH binding to the human melanocortin-2 receptor (MC2R) requires the presence of
      the MC2R accessory protein1 isoforms, MRAPalpha or MRAPbeta. This study evaluated
      the role of the isoform-specific C-terminal domains of MRAP with regard to their
      cellular localization, topology, interaction with MRAP2 and cAMP production. When
      stably expressed in HEK293/FRT cells or in B16-G4F mouse melanoma cells (an MSH
      receptor-deficient cell clone), MRAPalpha and MRAPdCT (truncated MRAP1, N
      terminal only) localized mainly around the nuclear envelope and within dense
      intracellular endosomes, while MRAPbeta exhibited a strong localization at the
      plasma membrane, and partially with rapid recycling endosomes. MRAPbeta and
      MRAPdCT both exhibited dual-topology (N(cyto)/C(exo) and N(exo)/C(cyto)) at the
      plasma membrane whereas MRAPalpha exhibited only N(cyto)/C(exo) topology at the
      plasma membrane while adopting dual-topology in intracellular compartments. Both
      MRAPalpha and MRAP2 colocalized in intracellular compartments, as opposed to weak
      colocalization between MRAPbeta and MRAP2. MRAP2 and MC2R enhanced the expression
      of MRAP1 isoforms and vice versa. Moreover, in both HEK293/FRT and B16-G4F cells,
      ACTH failed to activate MC2R unless MRAP1 was present. MRAP1 expression enhanced
      MC2R cell-surface expression as well as concentration-dependent cAMP
      accumulation. In the presence of human or zebrafish MC2R, MRAPbeta induced the
      highest cAMP accumulation while MRAPdCT induced the lowest. Together, the present
      findings indicate that the C-terminal domains of MRAP dictate their intracellular
      localization in addition to regulating ACTH-induced cAMP production. These
      preferential localizations suggest that MRAPalpha is involved in MC2R targeting
      to the plasma membrane, while MRAPbeta may enhance ACTH-MC2R coupling to cAMP
      production.

PMID- 22366473
TI  - Seasonal rhythms of salivary cortisol secretion in captive Asian elephants
      (Elephas maximus).
AB  - Salivary cortisol has been recently used to assess welfare of captive and free
      ranging animals. However, rhythms of cortisol secretion may vary annually and
      thus, it is necessary to take into account these rhythms when evaluating the
      physiological significance of fluctuations of this hormone throughout the year as
      stress indicator in animals. Here, we analyze monthly differences in cortisol
      secretion in Asian elephants (Elephas maximus) during a year. Saliva samples of
      eight adult female Asian elephants were collected and analyzed using
      Radioimmunoassay. Results revealed an overall seasonal pattern of salivary
      cortisol secretion and significant differences in cortisol concentration among
      months were found. Overall, the highest cortisol levels were recorded in October,
      and then decreased until reaching the lowest concentration in April. However,
      some individual variations were found respect this annual overall trend. The
      occurrence of this annual pattern of cortisol secretion should be taken into
      account when using cortisol as a tool to assess animal welfare in captive animal
      at zoological parks, as well as it opens new questions to further analyze this
      pattern and its variations, as well as the endogenous mechanisms controlling it.

PMID- 22366474
TI  - A novel combination of printed 3-dimensional anatomic templates and computer
      assisted surgical simulation for virtual preoperative planning in Charcot foot
      reconstruction.
AB  - Charcot foot syndrome (Charcot neuroarthropathy affecting the foot), particularly
      in its latter stages, may pose a significant technical challenge to the surgeon.
      Because of the lack of anatomic consistency, preoperative planning with virtual
      and physical models of the foot could improve the chances of achieving a
      predictable intraoperative result. In this report, we describe the use of a
      novel, inexpensive, 3-dimensional template printing technique that can provide,
      with just a normal printer, multiple "copies" of the foot to be repaired.
      Although we depict this method as it pertains to repair of the Charcot foot, it
      could also be used to plan and practice, or revise, 3-dimensional surgical
      manipulations of other complex foot deformities.

PMID- 22366475
TI  - Polytraumatization and trauma symptoms in adolescent boys and girls:
      interpersonal and noninterpersonal events and moderating effects of adverse
      family circumstances.
AB  - The objective of this study was to investigate the cumulative effect of
      interpersonal and noninterpersonal traumatic life events (IPEs and nIPEs,
      respectively) on the mental health of adolescents and to determine if the adverse
      impacts of trauma were moderated by adverse family circumstances (AFC).
      Adolescents (mean age 16.7 years) from the normative population (n = 462)
      completed the questionnaire, the Linkoping Youth Life Experience Scale (LYLES),
      together with Trauma Symptom Checklist for Children (TSCC). The lifetime
      accumulation of interpersonal, noninterpersonal, and AFC was independently
      related to trauma-related symptoms in both boys and girls. The number of AFCs
      moderated the mental health impact of both IPEs and nIPEs in boys but not in
      girls. Cumulative exposure to both interpersonal and noninterpersonal traumatic
      events is important for the mental health of adolescents, and, at least for boys,
      family circumstances seem to be relevant for the impact of trauma. Our results
      suggest that broader approaches to the study, prevention, and treatment of
      trauma, including consideration of cumulative exposure, different types of
      trauma, and additional social risk factors, could be fruitful.

PMID- 22366476
TI  - Examining gender differences in the nature and context of intimate partner
      violence.
AB  - Many studies have been conducted on gender differences in intimate partner
      violence (IPV), producing inconsistent results. Some studies report that men were
      victimized by IPV as much as women were, whereas others find that IPV was
      predominantly perpetrated by men against women. The nature and context of IPV may
      be crucial to understanding gender differences in IPV, but national data
      collections do not regularly report on this information. This study expects to
      fill this gap by using nationally representative data to examine differences in
      the nature and context of IPV between male and female perpetrators. This study
      uses the Collaborative Psychiatric Epidemiology Surveys (CPES). Descriptive
      statistics for each gender are first obtained (n = 2,190). A discriminant
      analysis is used with gender as a grouping variable, including only perpetrators
      of IPV (n = 236). The independent variables are age, race, education, employment,
      financial security, frequency and severity of IPV, controlling behaviors, and the
      initiator of physical arguments. The study findings suggest that women and men do
      not vary much in the prevalence, frequency, and severity of IPV, controlling
      behaviors, or the initiation of physical arguments. They also suggest that those
      variables are rather weak in differentiating IPV against men from IPV against
      women. Since the study revealed some gender differences in IPV and, at the same
      time, encountered methodological difficulties in convincingly showing them as
      real gender differences, more research is clearly needed.

PMID- 22366477
TI  - Reducing intimate and paying partner violence against women who exchange sex in
      Mongolia: results from a randomized clinical trial.
AB  - Women who exchange sex for money or other goods, that is, female sex workers, are
      at increased risk of experiencing physical and sexual violence from both paying
      and intimate partners. Exposure to violence can be exacerbated by alcohol use and
      HIV/STI risk. The purpose of this study is to examine the efficacy of a HIV/STI
      risk reduction and enhanced HIV/STI risk reduction intervention at decreasing
      paying and intimate partner violence against Mongolian women who exchange sex and
      engage in harmful alcohol use. Women are recruited and randomized to either (a)
      four sessions of a relationship-based HIV/STI risk reduction intervention (n =
      49), (b) the same HIV/STI risk reduction intervention plus two additional
      motivational interviewing sessions (n = 58), or (c) a four session control
      condition focused on wellness promotion (n = 59). All the respondents complete
      assessments at baseline (preintervention) as well as at immediate posttest, 3 and
      6 months postintervention. A multilevel logistic model finds that women who
      participated in the HIV/STI risk reduction group (OR = 0.14, p < .00), HIV/STI
      risk reduction and motivational interview group (OR = 0.46, p = .02), and
      wellness (OR = 0.20, p < .00) group reduced their exposure to physical and sexual
      violence in the past 90 days. No significant differences in effects are observed
      between conditions. This study demonstrates the efficacy of a relationship-based
      HIV/STI risk reduction intervention, a relationship-based HIV/STI risk reduction
      intervention combined with motivational interviewing, and a wellness promotion
      intervention in reducing intimate and paying partner violence against women who
      exchange sex in Mongolia. The findings have significant implications for the
      impact of minimal intervention and the potential role of peer networks and social
      support in reducing women's experiences of violence in resource poor settings.

PMID- 22366478
TI  - Full-length 3'-untranslated region reporter construction with recombineering.
AB  - Complexity in higher animals derives in part from various modalities of protein
      coding gene expression regulation, including microRNA repression by binding to 3'
      untranslated regions (UTRs) of specific genes. Reporter constructs containing
      candidate microRNA target sites are a popular approach of functional studies, and
      full-length 3'-UTR sequences are preferred because they contain all regulatory
      elements and preserve higher order structure as much as possible. However, this
      approach is often handicapped by the extreme length of the 3'-UTR. Here, we
      present a rapid and accurate cloning procedure to generate full-length 3'-UTR
      reporter constructs by recombinogenic engineering (recombineering) in vivo
      cloning. The approach includes making retrieval constructs by sequence- and
      ligation-independent cloning (SLIC) and retrieving the full-length 3'-UTR in one
      exon to the retrieval construct from a bacterial artificial chromosome (BAC) by
      recombineering to generate the final full-length 3'-UTR reporter construct for
      the gene of interest. This method is successfully implemented with mouse full
      length 3'-UTRs of Igf1 (6.5 kb), Igf1r (7.5 kb), and Sp1 (5.5 kb). Expansion of
      this method is adaptable to retrieve 3'-UTRs encoded in more than one exon by
      removing the introns from the BAC first with recombineering. This method will
      advance functional studies of regulation of gene expression at the post
      transcriptional level through microRNA suppression.

PMID- 22366479
TI  - Preventing retinal apoptosis--is there a common therapeutic theme?
AB  - There is an urgent need for therapies for retinal diseases; retinitis pigmentosa
      sufferers have no treatment options available and those targeted at other
      retinopathies have shown limited effectiveness. The process of programmed cell
      death or apoptosis although complex, remains a possible target for the treatment
      of retinal diseases. Having identified apoptosis in the vertebrate retina in
      populations of immature neurons as an essential part of development it was
      proposed that re-activation of these developmental cell death pathways might
      provide insight into the death mechanisms operating in retinal diseases. However,
      the discovery that numerous factors initiate and mediate the apoptotic cascade in
      mature photoreceptors has resulted in a relatively untargeted approach to
      examining and arresting apoptosis in the retina. In the last 5 years, mouse
      models have been treated with a diverse range of drugs or factors including anti
      oxidants, growth factors, steroid hormones, calcium/calpain inhibitors and
      tetracycline antibiotics. Therefore to draw a unifying theme from these broad
      research areas is challenging. However, this review focusses on two targets which
      are currently under investigation, reactive oxygen species and mammalian target
      of rapamycin, drawing together the common themes of these research areas.

PMID- 22366480
TI  - Interactive effects of maternal and environmental exposure to coal combustion
      wastes decrease survival of larval southern toads (Bufo terrestris).
AB  - We conducted a mesocosm study to assess the individual and interactive effects of
      previous maternal exposure and larval exposure to trace element-laden sediments
      on southern toads (Bufo terrestris). Previous maternal exposure to coal
      combustion wastes (CCW) reduced larval survival to metamorphosis up to 57%
      compared to larvae of unexposed females. Larvae reared on CCW accumulated
      significant concentrations of trace elements resulting in extended larval
      periods, reduced growth rates, and reduced mass at metamorphosis. However, the
      effects were dependent on age of sediments, suggesting the effects of
      contaminants from CCW may be partially ameliorated over time through the reduced
      bioavailability of trace elements in aged CCW. Most importantly, maternal
      exposure to contaminants coupled with larval exposure to fresh CCW interacted to
      reduce survival to metamorphosis by 85% compared to reference conditions. Our
      study yields further evidence that disposal of CCW in aquatic basins potentially
      creates ecological traps for some amphibian populations.

PMID- 22366481
TI  - Relationships between POPs and baseline corticosterone levels in black-legged
      kittiwakes (Rissa tridactyla) across their breeding cycle.
AB  - Chronic exposure to persistent organic pollutants (POPs) in wildlife might alter
      the response to environmental changes through interference with the regulation of
      stress hormones. Here, we examined the relationship between blood concentrations
      of several POPs and baseline plasma corticosterone levels in the black-legged
      kittiwake (Rissa tridactyla) during three distinct periods in the breeding
      season. The concentrations of POPs and corticosterone increased, whereas body
      mass decreased progressively from the pre-laying period to the incubation and the
      chick rearing period. ?PCB (polychlorinated biphenyls) correlated positively with
      the baseline corticosterone levels during the pre-laying period, which might
      suggest that PCBs affect the regulation of corticosterone. However, this
      relationship was not found during the incubation or the chick rearing period.
      Possible explanations are discussed with emphasis on how total stress/allostatic
      load is handled during different periods and conditions.

PMID- 22366482
TI  - Bioaccumulation of microcystins in two freshwater gastropods from a cyanobacteria
      bloom plateau lake, Lake Dianchi.
AB  - To investigate the bioaccumulation patterns of microcystins (MCs) in organs of
      two gastropods, samples were collected in Lake Dianchi monthly from May to
      October, 2008, when cyanobacteria typically bloom. The average MCs concentrations
      for Radix swinhoei (pulmonate) and Margarya melanioides (prosobranch) tended to
      be similar for the different organs: the highest values in the hepatopancreas
      (9.33 by 3.74 MUg/g DW), followed by digestive tracts (1.66 by 3.03 MUg/g DW),
      gonads (0.45 by 1.34 MUg/g DW) and muscles (0.22 by 0.40 MUg/g DW). Pulmonate had
      higher value than prosobranch because of the stronger bioaccumulation ability in
      hepatopancreas. The levels in organs of R. swinhoei were correlated with
      environmentally dissolved MCs, but influenced by intracellular MCs for M.
      melanioides. The estimated MCs concentrations in edible parts of M. melanioides
      were beyond the WHO's provisional tolerable daily intake (0.04 MUg/kg),
      suggesting the risk of consumption of M. melanioides from the lake.

PMID- 22366483
TI  - Gemcitabine-releasing polymeric films for covered self-expandable metallic stent
      in treatment of gastrointestinal cancer.
AB  - Non-vascular drug-eluting stents have been studied for the treatment of
      gastrointestinal cancer and cancer-related stenosis. In this study, we designed
      and evaluated a gemcitabine (GEM)-eluting covered nonvascular stent. Polyurethane
      (PU)/polytetrafluoroethylene (PTFE) film was selected for the drug loading and
      eluting membrane. The membrane was fabricated by dip-coating on a Teflon bar (?;
      10mm), air-dried, peeled off and applied to a self-expanding Nitinol stent.
      Various amounts of poloxamer 407 (PL, Lutrol F127, BASF) (8%, 10%, or 12% of PU
      by weight) were added to control the release of GEM from membranes. The membrane
      containing 12% PL (GEM-PU-PL12%) showed the most favourable release properties;
      70% of the loaded GEM released within 35 days, including the 35% released during
      the initial burst. The biological activities of GEM-PU-PL12% were evaluated using
      human cholangiocarcinoma cells (SK-ChA-1). GEM-PU-PL12% most efficiently
      inhibited the proliferation of cholangiocarcinoma cells and most highly induced
      pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-12) and p38 MAPKs in the
      cells. Subtumoural insertion of the GEM-PU-PL12% membrane more efficiently
      inhibited the growth of CT-26 colon cancer than other membranes. In this study,
      the GEM-eluting metal stents covered with PU-PL12% showed considerable
      feasibility for the treatment of malignant gastrointestinal cancer as well as
      cancer-related stenosis.

PMID- 22366484
TI  - An insight into the role of barrier related skin proteins.
AB  - It is well-known that intercellular lipids in the stratum corneum (SC) of the
      skin play an important role in maintaining barrier function, and many types of
      penetration enhancers affecting lipids are used in topical products to improve
      transdermal drug permeability. Recently, it was reported that functional proteins
      in tight junctions of the epidermis are important for barrier function. In this
      study, the effects of penetration enhancers such as fatty esters, amines/amides,
      and alcohols on the barrier function of the skin were evaluated in rat skin and
      normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers
      decreased the electrical impedance (EI), however, the potencies of some
      penetration enhancers were not equal between rat skin and NHEK. The differences
      were clarified by immunohistochemical studies: some fatty esters decreased the
      immunoreactivity of involucrin and keratin 10 in the upper layer of the
      epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin
      1, and E-cadherin located in the lower layer of the epidermis. From these
      results, it is suggested that penetration enhancers show new action mechanisms
      disturbing barrier-related proteins in epidermis, which are classified into two
      categories depending on their action sites.

PMID- 22366486
TI  - Fabrication of drug-loaded polymer microparticles with arbitrary geometries using
      a piezoelectric inkjet printing system.
AB  - Carrier geometry is a key parameter of drug delivery systems and has significant
      impact on the drug release rate and interaction with cells and tissues. Here we
      present a piezoelectric inkjet printing system as a simple and convenient
      approach for fabrication of drug-loaded polymer microparticles with well-defined
      and controlled shapes. The physical properties of paclitaxel (PTX)-loaded
      poly(lactic-co-glycolic acid) (PLGA) inks, such as volatility, viscosity and
      surface tension, were optimized for piezoelectric inkjet printing, and PTX-loaded
      PLGA microparticles were fabricated with various geometries, such as circles,
      grids, honeycombs, and rings. The resulting microparticles with 10% (w/w) PTX
      exhibited a fairly homogeneous shape and size. The microparticle fabrication by
      piezoelectric inkjet printing was precise, reproducible, and highly favorable for
      mass production. The microparticles exhibited a biphasic release profile with an
      initial burst due to diffusion and a subsequent, slow second phase due to
      degradation of PLGA. The release rate was dependent on the geometry, mainly the
      surface area, with a descending rate order of honeycomb>grid, ring>circle. The
      PTX-loaded microparticles showed a comparable activity in inhibiting the growth
      of HeLa cells. Our results demonstrate that a piezoelectric inkjet printing
      system would provide a new approach for large-scale manufacturing of drug
      carriers with a desired geometry.

PMID- 22366485
TI  - Improvement of survival in C6 rat glioma model by a sustained drug release from
      localized PLGA microspheres in a thermoreversible hydrogel.
AB  - A local drug delivery system based on sustained drug release is an attractive
      approach to treat brain tumors. We have developed a novel device using drug
      incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in
      thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation).
      TGP forms a gel at body temperature but sol at room temperature. Therefore, when
      this formulation is injected into the brain tumor, the PLGA microspheres in TGP
      gel are localized at the injection site and do not diffuse throughout the brain
      tissue; eventually, sustained drug release from PLGA microspheres is achieved at
      the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or
      vincristine (VCR)) were incorporated into PLGA microspheres to prepare
      drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher
      encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In
      addition, VCR/PLGA microspheres showed a higher sustained release profile than
      CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic
      effect (mean survival) was evaluated in the C6 rat glioma model (control group,
      18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33
      days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors
      (>60 days). Therefore, this formulation can be therapeutically effective
      formulation for the glioma therapy.

PMID- 22366487
TI  - [When congenital lung malformations have to be operated?].
AB  - Both technical and anatomical features and the need for a long follow-up, usually
      over several years, explain the specificity of lung surgery in children. Apart
      from the oncological resections, the main indications for this surgery are
      congenital lung anomalies (cystic adenomatoid malformation, bronchopulmonary
      sequestration, lobar emphysema), symptomatic postinfectious lesions
      (bronchiectasis, atelectasis, abscess) and pneumothorax. Advances in
      miniaturization of the surgical equipment are used to carry the majority of these
      interventions by thoracoscopy, except when performed at the neonatal period. In
      the newborn, for which the indications for lung surgical resections are
      exceptional, ventilatory conditions and the tightness of the chest lead to still
      prefer open surgery. Pulmonary malformations can also be managed prenatally when
      they affect lung development or cause heart failure because of compressive
      complications. These interventions, performed after the 30th week of gestation,
      are not intended to remove the lesions, but to release the compression. But these
      procedures are still under evaluation and, in light of possible fetal and
      maternal complications, they should only be performed in tertiary centers and in
      the context of specific protocols.

PMID- 22366488
TI  - Transporters for amino acids in plant cells: some functions and many unknowns.
AB  - Membrane proteins are essential to move amino acids in or out of plant cells as
      well as between organelles. While many putative amino acid transporters have been
      identified, function in nitrogen movement in plants has only been shown for a few
      proteins. Those studies demonstrate that import systems are fundamental in
      partitioning of amino acids at cellular and whole plant level. Physiological data
      further suggest that amino acid transporters are key-regulators in plant
      metabolism and that their activities affect growth and development. By contrast,
      knowledge on the molecular mechanisms of cellular export processes as well as on
      intracellular transport of amino acids is scarce. Similarly, little is known
      about the regulation of amino acid transporter function and involvement of the
      transporters in amino acid signaling. Future studies need to identify the missing
      components to elucidate the importance of amino acid transport processes for
      whole plant physiology and productivity.

PMID- 22366489
TI  - Molecular characterization of porcine SARM1 and its role in regulating TLRs
      signaling during highly pathogenic porcine reproductive and respiratory syndrome
      virus infection in vivo.
AB  - Toll-like receptors (TLRs) are important pattern-recognition receptors (PRRs)
      that trigger innate immune response and mediate acquired immunity. Evidence has
      shown that SARM1 (sterile-alpha and TIR motif containing protein 1) is one of
      five TIR domain-containing adaptor proteins involved in TLRs signaling
      transduction. In the present study, a full-length cDNA sequence was cloned for
      the porcine SARM1 gene, which contains nine exons. Using the radiation hybrid
      mapping approach, we assigned the porcine gene to SSC12 q13. Under the normal
      condition, porcine SARM1 was highly expressed in brain and spleen. Polyinosinic
      polycytidylic acid (poly (I:C)) weakly induced the porcine SARM1 expression in
      the early stimulation. We found that porcine SARM1 protein is localized in
      mitochondria and attenuates NF-kappaB activation induced by stimulation and
      infection. The quantitative real-time PCR (Q-PCR) analysis showed that the
      expression of porcine SARM1 significantly decreased in several tissues of
      Tongcheng pigs infected with highly pathogenic porcine reproductive and
      respiratory syndrome virus (HP-PRRSV). Gene-interaction network analysis for
      porcine SARM1 in porcine alveolar macrophages (PAMs) showed that down-regulation
      of SARM1 gene in infected Tongcheng pig may modulate TRIF-depend TLRs signaling
      and regulate the expression of disease-resistant genes and inflammatory genes.
      Our findings provide evidence that porcine SARM1 may play an important role in
      immune regulation with PRRSV infection.

PMID- 22366490
TI  - Looking to the future on the shoulders of giants.

PMID- 22366491
TI  - Variation in the use of intraoperative cholangiography during cholecystectomy.
AB  - BACKGROUND: The role of intraoperative cholangiography (IOC) in prevention of
      common bile duct (CBD) injuries and the management of CBD stones is
      controversial, and current variation in use of IOC has not been well described.
      STUDY DESIGN: Multilevel hierarchical models using data from the Texas Hospital
      Inpatient Discharge Public Use data files (2001 to 2008) were used to evaluate
      the percentage of variance in the use of IOC that was attributable to patient,
      surgeon, and hospital factors. RESULTS: A total of 176,981 cholecystectomies were
      performed in 212 hospitals in Texas. There was wide variation in IOC use, ranging
      from 2.4% to 98.4% of cases among surgeons and 3.7% to 94.8% of cases among
      hospitals, even after adjusting for case mix differences. The percentage of
      variance in IOC use attributable to the surgeon was 20.7% and an additional 25.7%
      was attributable to the hospital. IOC use was associated with increased age,
      gallstone pancreatitis or CBD stones, Hispanic race, decreased illness severity,
      insurance, and later year of cholecystectomy. ERCP (24.0% vs 14.9%, p < 0.0001)
      and CBD exploration (1.63% vs 0.42%, p < 0.0001) were more commonly performed in
      patients undergoing IOC. CONCLUSIONS: Uncertainty regarding the benefit of IOC
      leads to wide variation in use across surgeons and hospitals. The surgeon and
      hospital are more important determinants of IOC use than measured patient
      characteristics. Our study highlights the need for further evaluation of
      comparative effectiveness of IOC in the prevention of CBD injuries and retained
      stones, taking into account patient risk factors, surgeon skill, cost, and
      availability of local expertise.

PMID- 22366492
TI  - Microarray analysis of mediastinal lymph node of pigs naturally affected by
      postweaning multisystemic wasting syndrome.
AB  - Postweaning multisystemic wasting syndrome (PMWS) is one of the pig diseases with
      major economic impact worldwide. Clinical, pathologic and some immunologic
      aspects of this disease are relatively well-known, but the molecular mechanisms
      underlying the pathogenic mechanisms of the disease are still poorly understood.
      The objective of the present study was to investigate the global transcriptome
      changes in the mediastinal lymph nodes from pigs naturally affected by PMWS, as
      well as healthy counterparts, using the Affymetrix Porcine Genechip((r)). From
      366 transcripts showing significant differential abundance in the PMWS group of
      pigs relative to healthy animals, 229 showed higher and 137 lower abundance. A
      relative increased abundance of mRNAs coded by a large set of genes involved in
      the inflammatory responses (e.g. cytokines, acute phase proteins, and respiratory
      burst) was observed in PMWS affected pigs. The Gpnmb and Lgals3 genes, which have
      antagonistic functions in regulation of inflammatory processes, showed high mRNA
      levels in diseased pigs. The complement system was altered by PMWS, notably by
      the lower levels of Cr1 mRNA, which might favour both complement deposition and
      secondary infections by impairing phagocytosis. Decreased mRNA abundance of
      several genes involved in lymphocyte activation/differentiation, such as Cd79b,
      Cd19, Cd21 and MybL1, and the high level of Vsig4 mRNA, which can compromise the
      activation of residing T-cells, pointed towards a defective adaptive immunity.
      This is the first study on gene expression in pigs naturally affected by PMWS.
      The present results allowed identifying potential mechanisms underlying the
      inflammation and lymphocyte depletion in lymphoid tissues by complement mediated
      damage and immunosuppression, which are key features of PMWS.

PMID- 22366493
TI  - Using an E. coli Type 1 secretion system to secrete the mammalian, intracellular
      protein IFABP in its active form.
AB  - A biotechnological production of proteins through protein secretion systems might
      be superior to the conventional cytoplasmic production, because of the absence of
      large amounts of proteases present in the extracellular space and the ease of
      purification or downstream processing. However, secretion of proteins is still a
      trial-and-error approach and many proteins fail to be secreted. Recently, a study
      of a Type 1 secretion system revealed that the folding rate of the passenger
      protein dictates secretion efficiency. Here, the well-known MalE failed to be
      secreted when fused to a C-terminal fragment of the natural substrate haemolysin
      A. In contrast, slow-folding mutants of MalE were secreted in high yields.
      However, MalE is a bacterial protein that is targeted to the periplasmic space of
      E. coli and possesses the intrinsic capability to cross a membrane. Therefore, we
      applied the same approach for another eukaryotic protein that resides in the
      cytoplasm. As an example, we chose the intestinal fatty acid binding protein
      (IFABP) and highlight the universal potential of this Type 1 secretion system to
      secrete proteins with slow-folding kinetics (here the G121V mutant). Finally, a
      one-step purification protocol was established yielding 1mg of pure IFABP G121V
      per liter culture supernatant. Moreover, secreted IFABP G121V was shown to reach
      a folded state, which is biologically active.

PMID- 22366494
TI  - Comparison of external beam treatment techniques for T1-2, N0, M0 glottic
      cancers.
AB  - The purpose of this study was to compare 4 different external beam radiation
      therapy treatment techniques for the treatment of T1-2, N0, M0 glottic cancers:
      traditional lateral beams with wedges (3D), 5-field intensity-modulated radiation
      therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy.
      Treatment plans in each technique were created for 10 patients using consistent
      planning parameters. The photon treatment plans were optimized using Philips
      Pinnacle(3) v.9 and the IMRT and VMAT plans used the Direct Machine Parameter
      Optimization algorithm. The proton treatment plans were optimized using Varian
      Eclipse Proton v.8.9. The prescription used for each plan was 63 Gy in 28
      fractions. The contours for spinal cord, right carotid artery, left carotid
      artery, and normal tissue were created with respect to the patient's bony anatomy
      so that proper comparisons of doses could be made with respect to volume. An
      example of the different isodose distributions will be shown. The data collection
      for comparison purposes includes: clinical treatment volume coverage, dose to
      spinal cord, dose to carotid arteries, and dose to normal tissue. Data
      comparisons will be displayed graphically showing the maximum, mean, median, and
      ranges of doses.

PMID- 22366495
TI  - Lymph nodes metastasis is a risk factor for bone metastasis from extrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND/AIMS: The rate and site of bone metastasis from cholangiocarcinoma as
      well as the prognosis are unclear. Therefore, we intend to make a comparative
      review of the background to bone metastasis, examine a high-risk group for bone
      metastasis and use the data towards the improvement in quality of life.
      METHODOLOGY: We studied 200 cases of cholangiocarcinoma resected in our division
      from January 2003 to April 2010. RESULTS: Bone metastasis was confirmed in four
      cases (2.0%). The survival period after the diagnosis of bone metastasis ranged
      from 2.9 months to 21.6 months and the average was 6.7 months. We studied
      histopathological findings of bone metastasis, lymph node metastasis, lymphatic
      invasion, blood vessel invasion and perineural invasion (ly, v and pn) and found
      that all of four bone metastasis cases were positive for lymph node metastasis
      which was a statistically significant factor affecting bone metastasis.
      CONCLUSIONS: Since the number of cases we studied is small, it is difficult to
      determine whether lymph node metastasis is a risk factor for bone metastasis;
      however, we think it is necessary to take the probability of bone metastasis into
      consideration when we provide medical care to patients positive for lymph node
      metastasis.

PMID- 22366496
TI  - Different associations of estrogen receptor beta isoforms, ERbeta1 and ERbeta2,
      expression levels with tumor size and survival in early- and late-onset breast
      cancer.
AB  - BACKGROUND: In breast cancer, little is known about the consequences of co
      expression of ERalpha with the second estrogen receptor, ERbeta, and its isoforms
      in light of their joint prognostic value. Previously reported correlations have
      been based mostly on independent ERalpha and ERbeta expression levels in breast
      tumors. PURPOSE: To address whether the expression ratio of ERalpha and ERbeta
      and its isoforms may be a more important parameter than their absolute levels, we
      analyzed relative mRNA expression ratios of ERbeta1 to ERbeta2 and ERalpha in 74
      clinical samples of invasive breast cancer including 39 early-onset and 35 late
      onset breast cancers. Expression levels were correlated with clinical and
      histopathological parameters and disease-free interval. RESULTS: A specific
      correlation of ERbeta1 expression levels with tumor size was detected in early
      onset breast cancer patients and of ERbeta2 levels with tumor size in late-onset
      patients. Expression of both ERbeta isoforms inversely correlated with expression
      of the two estrogen regulated genes, progesterone receptor and pS2 in both
      groups. Higher levels of ERbeta2 than ERbeta1 isoform were associated with a
      better outcome in late-onset patients. CONCLUSIONS: Our results suggest that
      different isoforms of ERbeta may be involved in suppression of tumor growth in
      young and elder patients and may have different prognostic values.

PMID- 22366497
TI  - Inhibition of DNA-dependent protein kinase promotes ultrasound-induced cell death
      including apoptosis in human leukemia cells.
AB  - Ultrasound (US) has been shown to induce cell death in cancer cells; however, the
      underlying mechanism remains elusive. Here, we report a set of novel findings on
      the molecular mechanism. We found that Akt (also known as protein kinase B), a
      substrate of DNA-dependent protein kinase (DNA-PK), was phosphorylated in U937
      cells nullified with p53 or Molt-4 cells artificially abrogated with p53 after US
      exposure. On the contrary, Akt phosphorylation was transiently down-regulated
      then recovered in Molt-4 cells harboring wild-type p53 in US-exposed cells,
      possibly due to a mutual regulation between p53 and Akt. Inhibition of ataxia
      telangiectasia mutated (ATM) or DNA-PK revealed that DNA-PK, rather than ATM, was
      preferentially involved in Akt phosphorylation and cell survival after US
      exposure in all cell lines. These results indicate that DNA-PK plays a protective
      role against US-induced cell death regardless of p53 phenotype. In conclusion,
      our findings provide the first delineation of the role of DNA-PK in US-induced
      cell death and suggest that targeting DNA-PK might be a promising strategy to
      augment cancer eradication by US.

PMID- 22366498
TI  - Reconstruction of orbital wall defects: recommendations based on a mathematical
      model.

PMID- 22366499
TI  - Allocating risk capital for a brownfields redevelopment project under
      hydrogeological and financial uncertainty.
AB  - In this study, we defined risk capital as the contingency fee or insurance
      premium that a brownfields redeveloper needs to set aside from the sale of each
      house in case they need to repurchase it at a later date because the indoor air
      has been detrimentally affected by subsurface contamination. The likelihood that
      indoor air concentrations will exceed a regulatory level subject to subsurface
      heterogeneity and source zone location uncertainty is simulated by a physics
      based hydrogeological model using Monte Carlo realizations, yielding the
      probability of failure. The cost of failure is the future value of the house
      indexed to the stochastic US National Housing index. The risk capital is
      essentially the probability of failure times the cost of failure with a surcharge
      to compensate the developer against hydrogeological and financial uncertainty,
      with the surcharge acting as safety loading reflecting the developers' level of
      risk aversion. We review five methodologies taken from the actuarial and
      financial literature to price the risk capital for a highly stylized brownfield
      redevelopment project, with each method specifically adapted to accommodate our
      notion of the probability of failure. The objective of this paper is to develop
      an actuarially consistent approach for combining the hydrogeological and
      financial uncertainty into a contingency fee that the brownfields developer
      should reserve (i.e. the risk capital) in order to hedge their risk exposure
      during the project. Results indicate that the price of the risk capital is much
      more sensitive to hydrogeological rather than financial uncertainty. We use the
      Capital Asset Pricing Model to estimate the risk-adjusted discount rate to
      depreciate all costs to present value for the brownfield redevelopment project. A
      key outcome of this work is that the presentation of our risk capital valuation
      methodology is sufficiently generalized for application to a wide variety of
      engineering projects.

PMID- 22366501
TI  - M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition
      of type II vestibular hair cells.
AB  - There are two types of hair cells in the sensory epithelium of vestibular end
      organ. Type II vestibular hair cell (VHC II) is innervated by the efferent nerve
      endings, which employ a cholinergic inhibition mediated by SK channels through
      the activation of alpha9-containing nAChR. Our previous studies demonstrated that
      a BK-type cholinergic inhibition was present in guinea pig VHCs II, which may be
      mediated by an unknown mAChR. In this study, BK channel activities triggered by
      ACh were studied to determine the mAChR subtype and function. We found the BK
      channel was insensitive to alpha9-containing nAChR antagonists and m1, m3, m4
      muscarinic antagonists, but potently inhibited by the m2 muscarinic antagonist.
      Muscarinic agonists could mimic the effect of ACh and be blocked by m2
      antagonist. cAMP analog activated the BK current and adenyl cyclase (AC)
      inhibitor inhibited the ACh response. Inhibitor of Gialpha subunit failed to
      affect the BK current, but inhibitor of Gialpha and Gibetagamma subunits showed a
      potent inhibition to these currents. Our findings provide the physiological
      evidence that mAChRs may locate in guinea pig VHCs II, and m2 mAChRs may play a
      dominant role in BK-type cholinergic inhibition. The activation of m2 mAChRs may
      stimulate Gibetagamma-mediated excitation of AC/cAMP activities and lead to the
      phosphorylation of Ca(2+) channels, resulting in the influx of Ca(2+) and opening
      of the BK channel.

PMID- 22366500
TI  - Temporal modulation transfer functions measured from auditory-nerve responses
      following sensorineural hearing loss.
AB  - The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as
      characterized by temporal modulation transfer functions (TMTFs), generally shows
      a low-pass shape with a cut-off frequency that increases with fiber
      characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this
      result has been interpreted to suggest that peripheral filtering has a
      significant effect on limiting the encoding of higher modulation frequencies.
      Sensorineural hearing loss (SNHL), which is typically associated with broadened
      tuning, is thus predicted to increase the range of modulation frequencies
      encoded; however, perceptual studies have generally not supported this
      prediction. The present study sought to determine whether the range of modulation
      frequencies encoded by AN fibers is affected by SNHL, and whether the effects of
      SNHL on envelope coding are similar at all modulation frequencies within the TMTF
      passband. Modulation response gain for sinusoidally amplitude modulated (SAM)
      tones was measured as a function of modulation frequency, with the carrier
      frequency placed at fiber CF. TMTFs were compared between normal-hearing
      chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers
      had significantly broadened tuning. Synchrony and phase responses for individual
      SAM tone components were quantified to explore a variety of factors that can
      influence modulation coding. Modulation gain was found to be higher than normal
      in noise-exposed fibers across the entire range of modulation frequencies encoded
      by AN fibers. The range of modulation frequencies encoded by noise-exposed AN
      fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off
      frequencies. These results suggest that physiological factors other than
      peripheral filtering may have a significant role in determining the range of
      modulation frequencies encoded in AN fibers. Furthermore, these neural data may
      help to explain the lack of a consistent association between perceptual measures
      of temporal resolution and degraded frequency selectivity.

PMID- 22366502
TI  - Prehospital Trauma Life Support (PHTLS) training of ambulance caregivers and
      impact on survival of trauma victims.
AB  - BACKGROUND: The Prehospital Trauma Life Support (PHTLS) course has been widely
      implemented and approximately half a million prehospital caregivers in over 50
      countries have taken this course. Still, the effect on injury outcome remains to
      be established. The objective of this study was to investigate the association
      between PHTLS training of ambulance crew members and the mortality in trauma
      patients. METHODS: A population-based observational study of 2830 injured
      patients, who either died or were hospitalized for more than 24 h, was performed
      during gradual implementation of PHTLS in Uppsala County in Sweden between 1998
      and 2004. Prehospital patient records were linked to hospital-discharge records,
      cause-of-death records, and information on PHTLS training and the educational
      level of ambulance crews. The main outcome measure was death, on scene or in
      hospital. RESULTS: Adjusting for multiple potential confounders, PHTLS training
      appeared to be associated with a reduction in mortality, but the precision of
      this estimate was poor (odds ratio, 0.71; 95% confidence interval, 0.42-1.19).
      The mortality risk was 4.7% (36/763) without PHTLS training and 4.5% (94/2067)
      with PHTLS training. The predicted absolute risk reduction is estimated to
      correspond to 0.5 lives saved annually per 100,000 population with PHTLS fully
      implemented. CONCLUSIONS: PHTLS training of ambulance crew members may be
      associated with reduced mortality in trauma patients, but the precision in this
      estimate was low due to the overall low mortality. While there may be a relative
      risk reduction, the predicted absolute risk reduction in this population was low.

PMID- 22366503
TI  - The eMOSAIC model for humanoid robot control.
AB  - In this study, we propose an extension of the MOSAIC architecture to control real
      humanoid robots. MOSAIC was originally proposed by neuroscientists to understand
      the human ability of adaptive control. The modular architecture of the MOSAIC
      model can be useful for solving nonlinear and non-stationary control problems.
      Both humans and humanoid robots have nonlinear body dynamics and many degrees of
      freedom. Since they can interact with environments (e.g., carrying objects),
      control strategies need to deal with non-stationary dynamics. Therefore, MOSAIC
      has strong potential as a human motor-control model and a control framework for
      humanoid robots. Yet application of the MOSAIC model has been limited to simple
      simulated dynamics since it is susceptive to observation noise and also cannot be
      applied to partially observable systems. Our approach introduces state estimators
      into MOSAIC architecture to cope with real environments. By using an extended
      MOSAIC model, we are able to successfully generate squatting and object-carrying
      behaviors on a real humanoid robot.

PMID- 22366504
TI  - Stress responses of testosterone and corticosterone-binding globulin in a multi
      brooded species, Eurasian Tree Sparrows (Passer montanus): Does CBG function as a
      mediator?
AB  - In avian plasma, testosterone (T) and corticosterone (CORT) compete to bind with
      corticosterone-binding globulin (CBG). Elevation of CBG may function to "buffer"
      the tissues against high circulating levels of T and stress-induced levels of
      CORT. To demonstrate the effects of acute stress on CBG and T levels and their
      biological functions, we investigated seasonal changes of baseline and stress
      induced T and CBG levels in Eurasian Tree Sparrows (Passer montanus) during
      different life stages using the capture-handling-restraint stress method. Our
      results show that (1) male sparrows had significantly higher baseline T levels
      and CBG capacities during the nest building, the first egg-laying, and the first
      nestling stages, and significantly decreased stress-induced T levels only during
      the nest building and the first egg-laying stages. They also expressed
      significantly increased stress-induced CBG capacities during the second nestling
      stage. (2) Females showed significantly higher baseline CBG capacities but
      significantly decreased stress-induced CBG capacities during the nest building
      stage, and females also showed significantly increased stress-induced CBG
      capacities during the second egg-laying and the second nestling stages.
      Therefore, the seasonal fluctuations of baseline CBG in both sexes and baseline T
      in males reflect their adaptive strategies for optimizing their physiological and
      behavioral states to the life history cycle. The different patterns of stress
      induced CBG in females suggest CBG functions as an essential mediator in
      regulating stress response to unpredictable perturbations. Our results highlight
      the need for future studies of stress-induced CBG and T levels on a wide range of
      vertebrate species that vary in different life history stages to gain a full
      understanding of the mechanisms that underlie biological functions of CBG and T
      for unpredictable stressors.

PMID- 22366505
TI  - Corticosterone levels in host and parasite nestlings: is brood parasitism a
      hormonal stressor?
AB  - Parasite chicks from non-evictor species usually try to monopolize host parental
      care, thereby increasing considerably the level of food competition in the nest.
      Here, we propose that brood parasitism is an important stressor for host and
      parasite nestlings and explore this hypothesis in the non-evictor great spotted
      cuckoo (Clamator glandarius) and its main hosts, the same-sized black-billed
      magpie (Pica pica) and the larger carrion crow (Corvus corone). We experimentally
      created 3-nestling broods of different brood compositions (only cuckoo chicks,
      only host chicks, or cuckoo and host chicks together) and measured baseline
      corticosterone levels of nestlings along their developmental period (early,
      middle and late). We found that brood parasitism increased corticosterone levels
      in magpie nestlings in the mid and late nestling period compared to those raised
      in unparasitized nests. Interestingly, carrion crow nestlings from parasitized
      nests only increased their corticosterone levels in the mid nestling period, when
      the competition for food with the cuckoo nestling was highest. Our results
      suggest that brood parasitism could be a potential physiological stressor for
      host nestlings, especially during the developmental stages where food
      requirements are highest. Conversely, cuckoo nestlings could be physiologically
      adapted to high competition levels since they did not show significant
      differences in corticosterone levels in relation to brood composition.

PMID- 22366506
TI  - Progesterone impairs social recognition in male rats.
AB  - The influence of progesterone in the brain and on the behavior of females is
      fairly well understood. However, less is known about the effect of progesterone
      in the male system. In male rats, receptors for progesterone are present in
      virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the
      stria terminalis (BST) and the medial amygdala (MeA). This colocalization
      functions to regulate AVP expression, as progesterone and/or progestin receptors
      (PR)s suppress AVP expression in these same extrahypothalamic regions in the
      brain. These data suggest that progesterone may influence AVP-dependent behavior.
      While AVP is implicated in numerous behavioral and physiological functions in
      rodents, AVP appears essential for social recognition of conspecifics. Therefore,
      we examined the effects of progesterone on social recognition. We report that
      progesterone plays an important role in modulating social recognition in the male
      brain, as progesterone treatment leads to a significant impairment of social
      recognition in male rats. Moreover, progesterone appears to act on PRs to impair
      social recognition, as progesterone impairment of social recognition is blocked
      by a PR antagonist, RU-486. Social recognition is also impaired by a specific
      progestin agonist, R5020. Interestingly, we show that progesterone does not
      interfere with either general memory or olfactory processes, suggesting that
      progesterone seems critically important to social recognition memory. These data
      provide strong evidence that physiological levels of progesterone can have an
      important impact on social behavior in male rats.

PMID- 22366507
TI  - Chest pain caused by myocardial ischemia or not: sometimes the old handgrip test
      can solve the dilemma.
AB  - We describe the case of a patient with typical chest pain but negative maximal
      bicycle exercise-electrocardiogram test and for whom significant coronary artery
      disease was hypothesized by a positive handgrip exercise test and demonstrated by
      coronary angiography. Despite negative exercise stress test, handgrip as well as
      other provocative tests have to be considered when the pretest probability of
      coronary artery disease is intermediate and the symptoms are typical for angina.

PMID- 22366508
TI  - Successful steroid therapy for heart failure due to myocarditis associated with
      primary biliary cirrhosis.
AB  - This report concerns a 65-year-old woman with primary biliary cirrhosis (PBC)
      featuring high titers of M2 antimitochondrial antibody who developed intractable
      heart failure (HF). Although the etiology is unclear, involvement of skeletal
      muscles has been reported with PBC as a result of mitochondrial damage from the
      autoimmune process. In this case, histopathological examination and (18)F
      fluorodeoxy glucose-positron emission tomography imaging revealed myocarditis
      concomitant with myositis. The patient showed favourable response to high-dose
      corticosteroid administration. To the best of our knowledge, this is the first
      case of HF with myocarditis and polymyositis associated with asymptomatic PBC who
      was successfully treated with prednisolone.

PMID- 22366509
TI  - Referral and use of heart failure clinics: what factors are related to use?
AB  - BACKGROUND: Heart failure (HF) clinics have been shown to reduce hospital
      readmissions and generally have favourable effects on quality of life, survival,
      and care costs. This study investigated the rates of referral and use of HF
      clinics and examined factors related to program use. METHODS: This study
      represents a secondary analysis of a larger prospective cohort study conducted in
      Ontario. In hospital, 474 HF inpatients from 11 hospitals across Ontario
      completed a survey that examined predisposing, enabling, and need factors
      affecting HF clinic use. Then 1 year later, 271 HF patients completed a mailed
      survey that assessed referral to and use of HF clinics. RESULTS: Forty-one
      patients (15.2%) self-reported referral, and 35 (13%) self-reported attending an
      HF clinic. Generalized estimating equations showed that factors related to
      greater program use were having an HF clinic at the site of hospital recruitment
      (odds ratio [OR] = 8.40; P = 0.04), referral to other disease management programs
      (OR = 4.87; P = 0.04), higher education (OR = 4.61; P = 0.02), lower stress (OR =
      0.93; P = 0.03), and lower functional status (OR = 0.97; P = 0.03). CONCLUSION:
      Similar to previous research, only one-seventh of HF patients were referred to
      and used an HF clinic. Both patient-level and health-system factors were related
      to HF clinic use. Given the benefits of HF clinics, more research examining how
      equitable access can be increased is needed. Also, the appropriateness and cost
      repercussions of use of multiple disease management programs should be
      investigated.

PMID- 22366510
TI  - Lipoxin A4 analog attenuates morphine antinociceptive tolerance, withdrawal
      induced hyperalgesia, and glial reaction and cytokine expression in the spinal
      cord of rat.
AB  - Spinal neuroinflammation has been shown to play an important role in the
      development of morphine tolerance and morphine withdrawal-induced hyperalgesia.
      Lipoxins are endogenous lipoxygenase-derived eicosanoids that can function as
      "braking signals" in inflammation. The present study investigated the effect of 5
      (S), 6 (R)-lipoxin A4 methyl ester (LXA4ME), a stable synthetic analog of lipoxin
      A4, on the expression of antinociceptive tolerance and withdrawal-induced
      hyperalgesia in chronic morphine-treated rats. Chronic morphine administration
      through repeated subcutaneous injection induced the development of hyperalgesia
      and the expression of spinal antinociceptive tolerance to morphine. However,
      LXA4ME treatment significantly attenuated the development of hyperalgesia and the
      expression of spinal antinociceptive tolerance to intrathecal morphine in both
      mechanical and thermal test. Moreover, the administration of LXA4ME during the
      induction of morphine tolerance inhibited the activation of microglia and
      astrocytes; reduced the expression of proinflammatory cytokines interleukin-1beta
      (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha); upregulated the
      expression of anti-inflammatory cytokines IL-10 and transforming growth factor
      beta1 (TGF-beta1); and inhibited nuclear factor-kappa B (NF-kappaB) activation at
      the L5 lumbar spinal cord. These results suggest that treatment of LXA(4)ME
      provides a potential preventative or therapeutic approach for morphine tolerance
      and associated abnormal pain sensitivity.

PMID- 22366511
TI  - Pravastatin attenuates noise-induced cochlear injury in mice.
AB  - Noise-induced hearing loss (NIHL) is one of the most common forms of
      sensorineural hearing loss and a well-known contributor to presbycusis. Based on
      the generation of reactive oxygen species (ROS) in the pathogenesis of NIHL,
      augmentation of the antioxidative defense system is a major target for
      pharmacological prevention. In this study, we assessed whether administration of
      pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase,
      which is a rate-limiting enzyme of cholesterol synthesis, before noise exposure
      protects against cochlear injury in BALB/c mice. Noise exposure produced both
      compound threshold shift (CTS) and permanent threshold shift (PTS) over 40 dB at
      16 and 32 kHz. Pretreatment with pravastatin (25 mg/kg) for 5 days significantly
      decreased both CTS and PTS. Pravastatin also reduced hair cell death after noise
      exposure in the cochlea, which was identified by surface preparation and scanning
      electron microscopy (SEM). It also reduced the formation of noise-induced 4
      hydroxynonenal (4-HNE), a byproduct of lipid peroxidation. Activation of Rac1,
      one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase complex, which is a major superoxide generator in the cell membrane, was
      inhibited by the administration of pravastatin. These findings suggest that
      pravastatin can protect against cochlear acoustic injury by lowering ROS
      generation via inhibition of the formation of the NADPH oxidase complex. This
      study will be helpful for the development of new therapeutic strategies for NIHL
      and other hearing loss-related diseases caused by ROS overproduction.

PMID- 22366512
TI  - Phosphorylated mitogen-activated protein kinase/extracellular signal-regulated
      kinase 1/2 may not always represent its kinase activity in a rat model of focal
      cerebral ischemia with or without ischemic preconditioning.
AB  - The extracellular signal-regulated kinase (ERK) 1/2 protein requires a dual
      phosphorylation at conserved threonine and tyrosine residues to be fully
      activated under normal physiological conditions. Thus, ERK1/2 kinase activity is
      often defined by the quantity of phosphorylated kinase. However, this may not
      accurately represent its true activity under certain pathological conditions. We
      investigated whether ERK1/2 kinase activity is proportional to its
      phosphorylation state in a rat focal ischemia model with and without rapid
      ischemic preconditioning. We showed that phosphorylated-ERK1/2 protein levels
      were increased 2.6+/-0.07-fold, and ERK1/2 kinase activity was increased 10.6+/
      1.9-fold in animals receiving ischemic preconditioning alone without test
      ischemia compared with sham group (P<0.05, n=6/group), suggesting that
      phosphorylated-ERK1/2 protein levels represent its kinase activity under these
      conditions. However, preconditioning plus test ischemia robustly blocked ERK1/2
      kinase activity, whereas it increased phosphorylated-ERK1/2 protein levels beyond
      those receiving test ischemia alone, suggesting that phosphorylated-ERK1/2
      protein levels were not representative of actual kinase activity in this
      pathological condition. In conclusion, protein phosphorylation levels of ERK1/2
      do not always correspond to kinase activity, thus, measuring the true kinase
      activity is essential.

PMID- 22366513
TI  - The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlates
      with its inability to alter the metabolism of sphingolipids.
AB  - Fumonisins are mycotoxins frequently found as natural contaminants in maize,
      where they are produced by the plant pathogen Fusarium verticillioides. They are
      toxic to animals and exert their effects through mechanisms involving disruption
      of sphingolipid metabolism. Fumonisin B1 (FB1) is the predominant fumonisin in
      this family. FB1 is converted to its hydrolyzed analogs HFB1, by alkaline cooking
      (nixtamalization) or through enzymatic degradation. The toxicity of HFB1 is
      poorly documented especially at the intestinal level. The objectives of this
      study were to compare the toxicity of HFB1 and FB1 and to assess the ability of
      these toxins to disrupt sphingolipids biosynthesis. HFB1 was obtained by a
      deesterification of FB1 with a carboxylesterase. Piglets, animals highly
      sensitive to FB1, were exposed by gavage for 2 weeks to 2.8 MUmol FB1 or HFB1/kg
      body weight/day. FB1 induced hepatotoxicity as indicated by the lesion score, the
      level of several biochemical analytes and the expression of inflammatory
      cytokines. Similarly, FB1 impaired the morphology of the different segments of
      the small intestine, reduced villi height and modified intestinal cytokine
      expression. By contrast, HFB1 did not trigger hepatotoxicity, did not impair
      intestinal morphology and slightly modified the intestinal immune response. This
      low toxicity of HFB1 correlates with a weak alteration of the
      sphinganine/sphingosine ratio in the liver and in the plasma. Taken together,
      these data demonstrate that HFB1 does not cause intestinal or hepatic toxicity in
      the sensitive pig model and only slightly disrupts sphingolipids metabolism. This
      finding suggests that conversion to HFB1 could be a good strategy to reduce FB1
      exposure.

PMID- 22366514
TI  - A sensitivity analysis of process design parameters, commodity prices and
      robustness on the economics of odour abatement technologies.
AB  - The sensitivity of the economics of the five most commonly applied odour
      abatement technologies (biofiltration, biotrickling filtration, activated carbon
      adsorption, chemical scrubbing and a hybrid technology consisting of a
      biotrickling filter coupled with carbon adsorption) towards design parameters and
      commodity prices was evaluated. Besides, the influence of the geographical
      location on the Net Present Value calculated for a 20 years lifespan (NPV20) of
      each technology and its robustness towards typical process fluctuations and
      operational upsets were also assessed. This comparative analysis showed that
      biological techniques present lower operating costs (up to 6 times) and lower
      sensitivity than their physical/chemical counterparts, with the packing material
      being the key parameter affecting their operating costs (40-50% of the total
      operating costs). The use of recycled or partially treated water (e.g. secondary
      effluent in wastewater treatment plants) offers an opportunity to significantly
      reduce costs in biological techniques. Physical/chemical technologies present a
      high sensitivity towards H2S concentration, which is an important drawback due to
      the fluctuating nature of malodorous emissions. The geographical analysis
      evidenced high NPV20 variations around the world for all the technologies
      evaluated, but despite the differences in wage and price levels, biofiltration
      and biotrickling filtration are always the most cost-efficient alternatives
      (NPV20). When, in an economical evaluation, the robustness is as relevant as the
      overall costs (NPV20), the hybrid technology would move up next to BTF as the
      most preferred technologies.

PMID- 22366515
TI  - Membrane technology as a promising alternative in biodiesel production: a review.
AB  - In recent years, environmental problems caused by the use of fossil fuels and the
      depletion of petroleum reserves have driven the world to adopt biodiesel as an
      alternative energy source to replace conventional petroleum-derived fuels because
      of biodiesel's clean and renewable nature. Biodiesel is conventionally produced
      in homogeneous, heterogeneous, and enzymatic catalysed processes, as well as by
      supercritical technology. All of these processes have their own limitations, such
      as wastewater generation and high energy consumption. In this context, the
      membrane reactor appears to be the perfect candidate to produce biodiesel because
      of its ability to overcome the limitations encountered by conventional production
      methods. Thus, the aim of this paper is to review the production of biodiesel
      with a membrane reactor by examining the fundamental concepts of the membrane
      reactor, its operating principles and the combination of membrane and catalyst in
      the catalytic membrane. In addition, the potential of functionalised carbon
      nanotubes to serve as catalysts while being incorporated into the membrane for
      transesterification is discussed. Furthermore, this paper will also discuss the
      effects of process parameters for transesterification in a membrane reactor and
      the advantages offered by membrane reactors for biodiesel production. This
      discussion is followed by some limitations faced in membrane technology.
      Nevertheless, based on the findings presented in this review, it is clear that
      the membrane reactor has the potential to be a breakthrough technology for the
      biodiesel industry.

PMID- 22366516
TI  - Vector-initiated transitive RNA interference in the filamentous fungus
      Aspergillus oryzae.
AB  - RNA interference (RNAi), modulates gene expression via cleavage of double
      stranded RNA (dsRNA) by Dicer, producing 21-25 nucleotide silence-inducing RNAs
      (siRNAs). In association with Argonaute containing complexes, these siRNAs target
      sequence-specific degradation of the homologous single-stranded messenger RNA. In
      the majority of eukaryotes, degradation occurs within the boundaries of the dsRNA
      target. In Arabidopsis thaliana and Caenorhabditis elegans, gene silencing can
      also take place transitively, impacting transcripts from coding sequences that
      are adjacent to the intended target gene. Here we demonstrate effective
      transitive RNAi in the ascomycete Aspergillus oryzae. Fragments of 174 bp and 499
      bp derived from the A. oryzae wA gene involved in spore color development, were
      inserted immediately upstream of an inverted repeat derived from the Escherichia
      coli gene encoding for Hygromycin Phosphotransferase B (hph), which provided a
      double-stranded hph RNAi trigger. Introduction of this construct into A. oryzae
      host cells produced transformants with spores that were lighter in color than
      those of wild type. Real-time RT-qPCR analysis demonstrated a direct
      correspondence of steady-state wA mRNA level to spore color. An A. oryzae strain
      deficient in RNA-dependent RNA Polymerase (RdRP) produced exclusively wild type
      colored spores when transformed with a wA transitive RNAi construct. Conversely,
      increased expression of RdRP enhanced the incidence of wA gene silencing via
      transitive RNAi.

PMID- 22366517
TI  - Platelet-rich plasma stimulates cell proliferation and enhances matrix gene
      expression and synthesis in tenocytes from human rotator cuff tendons with
      degenerative tears.
AB  - BACKGROUND: Platelet-rich plasma (PRP) contains various growth factors and
      appears to have a potential to promote tendon healing, but evidence is lacking
      regarding its effect on human tenocytes from rotator cuff tendons with
      degenerative tears. HYPOTHESIS: Platelet-rich plasma stimulates cell
      proliferation and enhances matrix gene expression and synthesis in tenocytes
      isolated from human rotator cuff tendons with degenerative tears. STUDY DESIGN:
      Controlled laboratory study. METHODS: Tenocytes were enzymatically isolated and
      cultured. To evaluate cell proliferation, tenocytes were cultured with 10%
      (vol/vol) platelet-poor plasma (PPP), PRP activated with calcium, and PRP
      activated with calcium and thrombin at platelet concentrations of 100, 200, 400,
      800, 1000, 2000, 4000, 8000, and 16,000 * 10(3)/uL for 14 days. Cell number was
      measured at days 7 and 14. To investigate matrix gene expression and synthesis,
      cells were cultured with a PPP or PRP gel (10% vol/vol) at a platelet
      concentration of 1000 * 10(3)/uL for 14 days. Quantitative real-time reverse
      transcriptase polymerase chain reaction was performed to determine the
      expressions of type I and III collagen, decorin, tenascin-C, and scleraxis, and
      measurements of total collagen and glycosaminoglycan (GAG) synthesis were
      conducted at days 7 and 14. RESULTS: Platelet-rich plasma significantly increased
      cell proliferation at days 7 and 14 in a dose-dependent manner, and the addition
      of thrombin moved up the plateau of proliferation. Platelet-rich plasma
      significantly induced the gene expression of type I collagen at day 7 but not at
      day 14, while it significantly promoted that of type III both at days 7 and 14.
      The ratio of type III/I collagens did not change at days 7 and 14. The
      expressions of decorin and scleraxis significantly increased at day 14, whereas
      that of tenascin-C significantly increased at days 7 and 14. Platelet-rich plasma
      significantly increased total collagen synthesis at days 7 and 14 and GAG
      synthesis at day 14. CONCLUSION: Platelet-rich plasma promoted cell proliferation
      and enhanced gene expression and the synthesis of tendon matrix in tenocytes from
      human rotator cuff tendons with degenerative tears. CLINICAL RELEVANCE: These
      findings suggest that PRP might be used as a useful biological tool for
      regenerative healing of rotator cuff tears by enhancing the proliferation and
      matrix synthesis of tenocytes from tendons with degenerative tears.

PMID- 22366518
TI  - Osteochondral lesions of the talus: effect of defect size and plantarflexion
      angle on ankle joint stresses.
AB  - BACKGROUND: Osteochondral lesions of the talus (OLTs) are a common cause of ankle
      pain and disability. Current clinical guidelines favor autogenous or allogenic
      osteochondral grafting procedures for lesions larger than 10 mm in diameter
      because of increased failure rates in these larger lesions with arthroscopic
      debridement, curettage, and microfracture. There are currently no biomechanical
      data nor level I clinical data supporting this size threshold. PURPOSE: The
      purpose of this study was to determine the effect of OLT defect size on stress
      concentration, rim stress, and location of peak stress and whether a threshold
      defect size exists. STUDY DESIGN: Descriptive laboratory study. METHODS:
      Progressively larger medial OLTs were created (6, 8, 10, and 12 mm) in 8 fresh
      frozen cadaveric ankle joints. With a calibrated Tekscan pressure sensor in the
      tibiotalar joint, an axial load of 686 N was applied, and pressure was recorded
      in neutral and 15 degrees  of plantar flexion with each defect size. Peak stress,
      contact area, peak and average rim stresses, and location of peak stress were
      determined. RESULTS: The distance between peak stress and defect rim was
      significantly decreased with increasing defect size for lesions of 10 mm and
      larger. Total tibiotalar contact area was significantly decreased with increasing
      defect size and with ankle plantar flexion. While peak joint stress and peak rim
      stress were not affected by defect size or plantar flexion, average rim stress
      was significantly increased by plantar flexion. CONCLUSION: Reduction in contact
      area and shift in the location of peak stress with increasing defect size may
      contribute to articular cartilage degeneration, pain, and defect enlargement in
      patients with OLTs. There appears to be a threshold of 10 mm after which the
      distance between the rim of the defect and the peak stress decreases; however,
      there is no change in peak stress magnitude with increasing defect size. CLINICAL
      RELEVANCE: The location of peak stress in the ankle joint becomes closer to the
      rim of the defect in OLTs at a threshold of 10 mm and greater in diameter. These
      data may have implications toward OLT size thresholds for surgical decision
      making in symptomatic lesions (ie, primary osteochondral transplantation
      procedure vs curettage and debridement). The ultimate goal is to determine
      whether there is a threshold defect size for primary osteoarticular graft
      techniques.

PMID- 22366519
TI  - Ultrasound as a primary evaluation tool of bone stress injuries in elite track
      and field athletes.
AB  - BACKGROUND: Little is known about therapeutic ultrasound (TUS) to diagnose bone
      stress injuries. HYPOTHESIS: Therapeutic ultrasound is an accurate, cost
      efficient alternative to other imaging methods for primary assessment of bone
      stress injuries. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: One hundred thirteen elite track and field athletes (mean age, 20.1
      years; range, 17-28 years) underwent TUS and magnetic resonance imaging (MRI) for
      clinical suspicion of a bone stress injury. A 5-stage MRI grading system was used
      to classify bone stress injuries. Sensitivity, specificity, accuracy, and
      positive and negative predictive values of TUS were calculated using MRI as the
      standard for diagnosis. RESULTS: At MRI, of 113 assessed patients, 3 (2.7%) had
      grade 0 injuries, 12 (10.6%) had grade 1, 15 (13.3%) had grade 2, 77 (68.2%) had
      grade 3, and 6 (5.3%) had grade 4. At TUS, no injury was detected in 22 of 113
      patients: 2 with grade 0 injury, 8 with grade 1, 8 with grade 2, and 4 with grade
      3. Using MRI as the gold standard, TUS showed 81.8% sensitivity, 66.6%
      specificity, 99.0% positive predictive value, 13.4% negative predictive value,
      and 81.4% accuracy. CONCLUSION: Therapeutic ultrasound is a reproducible
      procedure that is reliable to diagnose bone stress injuries.

PMID- 22366520
TI  - Molecular characterization of a new hypovirus infecting a phytopathogenic fungus,
      Valsa ceratosperma.
AB  - A double-stranded (ds) RNA, approximately 9.5kb in size; was identified in the
      MVC86 isolate of Valsa ceratosperma. Complete sequence of the dsRNA revealed a
      9543-bp segment (excluding the 3' poly-A tail) that is predicted to encode a
      single large protein (P330). P330 has 63%, 49%, and 55% amino acid sequence
      identities to the proteins encoded by hypoviruses Cryphonectria hypovirus 3
      (CHV3), CHV4, and Sclerotinia sclerotiorum hypovirus 1 (SsHV1), respectively.
      Like polyproteins encoded by CHV3, CHV4, and SsHV1, P330 comprises four conserved
      domains, including a papain-like protease, a UDP glucose/sterol
      glucosyltransferase (UGT), an RNA-dependent RNA polymerase (RdRp), and an RNA
      helicase. These molecular characteristics suggest that this dsRNA represents a
      new hypovirus that we tentatively designate Valsa ceratosperma hypovirus 1
      (VcHV1). Phylogenetic analysis of the RdRp and RNA helicase domains of VcHV1
      revealed that VcHV1, CHV3, CHV4, and SsHV1 clustered together into one clade
      distinct from that of CHV1 and CHV2, indicating the existence of two lineages in
      the family Hypoviridae. Comparison of biological properties between VcHV1
      infected and VcHV1-free isogenic strains did not reveal differences in colony
      morphology or fungal virulence under laboratory conditions.

PMID- 22366521
TI  - Positive and negative regulation in the promoter of the ORF46 gene of Kaposi's
      sarcoma-associated herpesvirus.
AB  - The ORF46 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes uracil
      DNA glycosylase, an enzyme involved in DNA repair. In this study, we show that
      the transcriptional start site of the ORF46 gene is located at nucleotide 69,425
      of the viral genome and ORF50 protein, a latent-lytic switch transactivator,
      activates the ORF46 promoter via RBP-Jkappa protein. Three consensus RBP-Jkappa
      binding sites found in the ORF46 promoter are critical for the binding of RBP
      Jkappa protein and conferring the ORF50 responsiveness. In addition, a negative
      regulatory region has been determined in the ORF46 promoter, which mediates the
      suppression of the ORF50 responsiveness. The functional negative region of the
      ORF46 promoter is mainly composed of the Sp1-binding sites. Like the negative
      region of the ORF46 promoter, addition of Sp1-binding sequences alone in an ORF50
      responsive promoter efficiently confers the suppression of the ORF50
      responsiveness. Furthermore, sodium butyrate, a pleiotropic inducing agent for
      the KSHV lytic cycle, is able to relieve the negative regulation of the ORF46
      promoter in the latently KSHV-infected cells. The identification of multiple
      positive and negative cis-acting regulatory elements in the viral promoters
      emphasizes the elaborate controls in the KSHV lytic cycle, which ensure the
      adequate expression of each viral lytic gene.

PMID- 22366522
TI  - Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC
      SIGN on dendritic cells.
AB  - Cancer immunotherapy requires potent tumor-specific CD8(+) and CD4(+) T-cell
      responses, initiated by dendritic cells (DCs). Tumor antigens can be specifically
      targeted to DCs in vivo by exploiting their expression of C-type lectin receptors
      (CLR), which bind carbohydrate structures on antigens, resulting in
      internalization and antigen presentation to T-cells. We explored the potential of
      glycan-modified liposomes to target antigens to DCs to boost murine and human T
      cell responses. Since DC-SIGN is a CLR expressed on DCs, liposomes were modified
      with DC-SIGN-binding glycans Lewis (Le)(B) or Le(X). Glycan modification of
      liposomes resulted in increased binding and internalization by BMDCs expressing
      human DC-SIGN. In the presence of LPS, this led to 100-fold more efficient
      presentation of the encapsulated antigens to CD4(+) and CD8(+) T-cells compared
      to unmodified liposomes or soluble antigen. Similarly, incubation of human moDC
      with melanoma antigen MART-1-encapsulated liposomes coated with Le(X) in the
      presence of LPS led to enhanced antigen-presentation to MART-1-specific CD8(+) T
      cell clones. Moreover, this formulation drove primary CD8(+) T-cells to
      differentiate into high numbers of tetramer-specific, IFN-gamma-producing
      effector T-cells. Together, our data demonstrate the potency of a glycoliposome
      based vaccine targeting DC-SIGN for CD4(+) and CD8(+) effector T-cell activation.
      This approach may offer improved options for treatment of cancer patients and
      opens the way to in situ DC-targeted vaccination.

PMID- 22366523
TI  - Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic
      differentiation and maturation with up-regulation of CB1 and CB2.
AB  - Three-dimensional scaffolds like hydrogels can be used for cell and drug delivery
      and have become a major research focus in tissue engineering. Presently, we
      investigated the regenerative potency of platelet-rich plasma (PRP) combined with
      a chondrocyte/hydrogel composite scaffold in the repair of articular cartilage
      defects using a rabbit model. Primary isolated joint chondrocytes from the
      trachlear groove of rabbit were cultured in hydrogels as follows; hydrogel (2900
      Pa or 5900 Pa)+chondrocytes and hydrogel+chondrocytes+PRP for in vitro analysis
      and in vivo implantation. The 5900 Pa hydrogel markedly increased cellular
      viability and development in a time-dependent manner. Furthermore, the hydrogels
      attenuated the expression of SOX-9, aggrecan, and type II collagen. PRP
      containing hydrogels produced an immediate increase in mRNA levels of cannabinoid
      receptor (CB)1 and CB2, compared with control and PRP-free hydrogels.
      Osteochondral defects were enhanced recovery with formation of cartilage and
      perichondrium in the 5900 Pa hydrogel+chondrocytes+PRP. Hydrogel may provide a
      suitable environment for proliferation and maturation of joint chondrocytes in
      relation to the gelation density and bioactive sources like PRP resulting in
      improvement for cartilage regeneration.

PMID- 22366524
TI  - Capitalization and proximity to agricultural and natural lands: evidence from
      Delaware.
AB  - This paper offers an applied study assessing the price impacts of proximity to
      open space in a residential property market. Data are collected in an urban
      influenced region of Delaware, USA, which has experienced rapid population growth
      -an 85 percent increase in number of households and 92 percent increase in
      population between Census 1990 and Census 2000--but also maintains substantial
      agricultural land use. In agreement with previous literature the results show the
      protection of agricultural and natural lands is capitalized into the value of
      neighboring properties. Surprisingly however, in this rapidly growing region the
      open space that is not protected from development offers no distinguishable
      effect on property values. This is likely because in a rapidly developing region
      all unprotected land is seen as potentially developable.

PMID- 22366525
TI  - A pilot trial of S-1 plus irinotecan chemotherapy for esophageal adenocarcinoma.
AB  - BACKGROUND/AIMS: This study investigated the clinical efficacy and toxicity of
      the combination chemotherapy using S-1 plus irinotecan for esophageal
      adenocarcinoma. METHODOLOGY: This study included 10 patients with histologically
      confirmed adenocarcinoma of the esophagus or esophagogastric junction between
      April 2005 and August 2011. S-1 was administered orally at a dose of 80 mg/m2/day
      from day 1 to 14 and irinotecan was given intravenously on day 1 and 8 at a dose
      of 80 mg/m2. RESULTS: A total of 65 cycles were administered and the response
      rate was 62.5%. The 50% progression-free survival period and the 50% overall
      survival period for all of the patients was 8.4 months and 19.1 months,
      respectively and 5.9 months and 16.3 months for the 8 patients with unresectable
      or recurrent tumors, respectively. The 2 patients that received adjuvant
      chemotherapy demonstrated a prophylactic effect for the post-operative
      recurrence. On the other hand, this therapy showed no severe non-hematological
      toxicity and only 20% experienced grade 3 neutropenia. As a result, the treatment
      regimen could generally be performed in an outpatient basis. CONCLUSIONS: The
      combination chemotherapy using S-1 and irinotecan showed tolerable clinical
      efficacy in terms of the response rate, survival and toxicity for esophageal
      adenocarcinoma.

PMID- 22366526
TI  - Fast track rehabilitation programme enhances functional recovery after
      laparoscopic colonic resection.
AB  - BACKGROUND/AIMS: Fast track (IT) rehabilitation programmes have demonstrated
      advantages over traditional perioperative care after open colonic surgery;
      however. their contribution in recovery after laparoscopic colonic surgery is not
      clearly defined. This study was conducted to estimate the value of FT
      rehabilitation programme in laparoscopic colonic resections. METHODOLOGY: This is
      a randomized prospective controlled clinical trial. Ninety-nine consecutive
      patients underwent elective laparoscopic colonic resection between February 2008
      and March 2009. Forty-nine patients received FT multimodal rehabilitation
      programme as FT group and 50 patients underwent traditional perioperative care as
      non-FT group. Postoperative hospital stay, return of gastrointestinal function,
      postoperative complications were recorded. RESULTS: Postoperative hospital stay
      was shorter in the FT group, a median duration of 4.0 days versus 5.0 days in the
      non-FT group (p<0.01). Gastrointestinal functional recovery occurred 1 day
      earlier in FT group (passage of flatus after 2.0 days vs. 3.0 days, p<0.01).
      There were no significant differences in complications within 30 postoperative
      days (12% in FT group vs. 20% in non-FT group, p=0.295). CONCLUSIONS: When
      applied after laparoscopic colonic surgery, FT rehabilitation programme is
      feasible, safe and may lead to accelerated functional recovery and reductions in
      postoperative hospital stay.

PMID- 22366527
TI  - Clinicopathological analysis of distal margin for rectal cancer after
      preoperative chemoradiation therapy.
AB  - BACKGROUND/AIMS: Preoperative chemoradiation therapy (CRT) for advanced rectal
      cancer allows anal sphincter preservation in some patients who would require an
      abdominoperineal resection. But adequate distal margin in patients with locally
      advanced rectal cancer requiring preoperative CRT is unclear. The objective was
      to evaluate necessary distal margin from reduced tumor by preoperative CRT for
      anal sphincter preservation. METHODOLOGY: This study included 11 consecutive
      patients who performed low anterior resection and abdominoperineal resection for
      rectal cancer after preoperative CRT. Distal margin length from reduced tumor by
      preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis
      stage and pathological changes of tumors were examined. RESULTS: Length from anal
      side edge of reduced tumor by preoperative CRT to pathological residual tumor
      ranged from +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0,
      M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence
      occurred in one patient and was distant and not local. Pathological examinations
      showed that no patient had lymph-node-metastasis and residual tumors by
      preoperative CRT. CONCLUSIONS: This study suggests that for patients with locally
      advanced rectal cancer undergoing resection and preoperative CRT, distal margins
      >=1 cm from reduced tumor by preoperative CRT seem to compromise pathological
      outcome.

PMID- 22366528
TI  - A case-control study of correlation between preoperative serum AFP and recurrence
      of hepatocellular carcinoma after curative hepatectomy.
AB  - BACKGROUND/AIMS: The prognostic impact of serum alpha-fetoprotein (AFP) on
      patients with hepatocellular carcinoma (HCC) undergoing curative resection
      remains unclear. We conducted a case-control study to investigate it.
      METHODOLOGY: A total of 196 HCC patients with negative preoperative AFP were
      admitted and treated by curative liver resection. During the same period, 196
      patients with positive preoperative AFP were enrolled to match the TN M stages,
      Child-Pugh score and HBs-Ag status of the AFP-negative patients. Time to
      recurrence (TTR) and overall survival (OS) were prospectively studied. RESULTS:
      Through a median follow-up duration of 5.25 years, we found that the median TTR
      of patients with negative preoperative AFP was significantly longer than those
      with positive AFP (17.3 vs. 12.8 months, p=0.001). The median TTRs of AFP
      negative and positive patients were 22.1 and 21.0 months (p=0.266), 145 and 7.4
      months (p=0.005) and 3.7 and 2.9 months (p=0.197) in TNM stages I, II and IIIa,
      respectively. The median TTRs of TNM stage II patients with :<=20, 20-400, 400
      1000 and >1000 ng/mL preoperative AFP concentration were 14.5, 13.7, 10.7 and 9.6
      months (p=0.092), respectively. CONCLUSIONS: Preoperative AFP level is an
      independent prognostic factor affecting postoperative recurrence in HCC patients
      and correlated with the TTR of TNM II.

PMID- 22366529
TI  - Differential expression of ghrelin mRNA according to anatomical portions of human
      stomach.
AB  - BACKGROUND/AIMS: The detailed ghrelin distribution on mRNA level in different
      anatomical portions of adult stomach and its association with plasma ghrelin
      levels are not yet well established. We investigated the ghrelin mRNA and peptide
      expression in different anatomical portions of stomach in human adults.
      METHODOLOGY: Stomach tissue samples were obtained from 16 patients with gastric
      cancer who underwent total gastrectomy. The normal stomach tissues were taken
      from the upper (gastric fundus and upper body), middle (gastric middle and lower
      body) and lower (gastric antrum and pylorus) portions of stomach, respectively.
      The expression of ghrelin mRNA and peptide in stomach tissue samples were
      measured using RT-PCR and immunohistochemistry. RESULTS: The ghrelin/actin ratio
      was 0.78 (range 0-3.38; n=16) at the upper portion, 0.20 (range 0-1.28; n=16) at
      the middle portion and 0.07 (range 0-0.67; n=16) at the lower portion of the
      stomach (p=0.001). Ghrelin-positive cells were seen in all parts of the gastric
      mucosa and were most numerous in the glandular compartment compared to foveolar
      compartment. Gastric body or fundic mucosa showed ghrelin-positive cells most
      abundantly as compared to other portions of the gastric mucosa (p<0.001).
      CONCLUSIONS: Ghrelin mRNA expression and immunoreactivity is highest at the upper
      portion of the human stomach.

PMID- 22366530
TI  - A promoter variant in the chitinase 3-like 1 gene is associated with serum YKL-40
      level and personality trait.
AB  - The chitinase 3-like 1 (CHI3L1) gene, a cellular survival factor against several
      environmental and psychosocial stresses, has been sown to be more highly
      expressed in the hippocampus and prefrontal cortex of patients with schizophrenia
      than unaffected individuals. We recently reported a significant association
      between schizophrenia and SNP rs4950928, which is located in the promoter region
      of the CHI3L1 gene, in a Japanese population. The G-allele at this SNP in the
      gene has been associated with higher transcriptional activity in a luciferase
      reporter assay and with higher mRNA levels in the peripheral blood cells of
      patients with schizophrenia. We investigated the impact of the CHI3L1
      polymorphism rs4950928 on serum YKL-40 levels, the protein product of CHI3L1. We
      found that individuals with the G-allele, who were more prevalent among patients
      with schizophrenia, had significantly higher serum YKL-40 levels (p=0.043).
      Personality traits are considered to be an important aspect of schizophrenia
      primarily because they may influence symptoms and social functioning. Personality
      trait analyses using the temperament and character inventory (TCI) indicated that
      schizophrenic patients have a unique personality profile that appears to be
      present across cultures. We hypothesized that higher serum YKL-40 levels are
      associated with personality trait in patients with schizophrenia. Thus, we next
      examined the impact of the risk CHI3L1 polymorphism on personality traits using
      the TCI. We found that individuals with the G-allele had significantly higher
      self-transcendence scores (p=0.0054). These findings suggest possible
      associations between the SNP in the CHI3L1 gene, the risk for schizophrenia, and
      higher serum YKL-40 levels and personality traits in a Japanese population.

PMID- 22366531
TI  - Screens, maps & networks: from genome sequences to personalized medicine.
AB  - Genome sequencing of tumors provides a wealth of information on mutations and
      structural variations, instilling hope that this data can be used to predict
      individual tumor progression and response to treatment. Yet currently, our
      ability to predict the functional consequences of these aberrations remains poor.
      How do cancer-associated mutations give rise to the hallmark phenotypes of
      cancer? Recently, information about the genetic makeup of cancer cells has been
      combined with novel functional genomics approaches to identify novel targets,
      exploit synthetic lethality and explore the rewiring of cellular pathways. Here,
      we highlight recent developments revealing the hidden landscape of genetic
      interactions in model organisms and cancer cells, a key step toward personalized
      cancer diagnostics and therapy.

PMID- 22366532
TI  - Genome instability mechanisms and the structure of cancer genomes.
AB  - Genomic instability is a hallmark of cancer cells, and arises from the
      aberrations that these cells exhibit in the normal biological mechanisms that
      repair and replicate the genome, or ensure its accurate segregation during cell
      division. Increasingly detailed descriptions of cancer genomes have begun to
      emerge from next-generation sequencing (NGS), providing snapshots of their nature
      and heterogeneity in different cancers at different stages in their evolution.
      Here, we attempt to extract from these sequencing studies insights into the role
      of genome instability mechanisms in carcinogenesis, and to identify challenges
      impeding further progress.

PMID- 22366533
TI  - Ethnomedicinal knowledge, belief and self-reported practice of local inhabitants
      on traditional antimalarial plants and phytotherapy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper reveals the trend of knowledge and
      practice of traditional antimalarial plants (TAPs) to prevent/treat malaria.
      MATERIALS AND METHODS: Stratified, systematic random sampling was adopted. The
      ethnomedicinal survey was conducted between January and March 2011 by involving
      the selected 371 household members on knowledge and practice of TAPs by
      administering a pre-tested questionnaire. RESULTS: Overall, 54.4% respondents had
      adequate awareness and usage custom of TAPs and 16 types of plant have been most
      commonly known and employed by the respondents to prevent/treat malaria. Leaves
      (57.2%) were most commonly used plant part to prepare traditional antimalarial
      phytotherapy remedies. Decoction was one of the most commonly used methods to
      administer TAPs. The chi-square test result revealed that a significant
      association is found between the usage custom of traditional antimalarial plants
      and gender (P-value=0.0282), age (P-value=0.0024), educational status (P
      value=0.0295), and monthly income (P-value=0.0001), although not with the
      ethnicity (P-value=0.7933) of the respondents. CONCLUSION: TAPs usage is an
      integral part of the tradition and custom of the Ethiopians. However, nearly half
      of the respondents have had lack of awareness about TAPs and majority of them are
      reluctant in exercising either due to its ineffectiveness or its bitter taste.
      Therefore, further laboratory-based research is extremely imperative to identify
      their antiplasmodial activity and bioactive molecules which could pave the way to
      formulate the novel affordable as well as accessible potent antimalarials in the
      near future.

PMID- 22366534
TI  - Increasingly certain about uncertainty: Intolerance of uncertainty across anxiety
      and depression.
AB  - Intolerance of uncertainty (IU) - a dispositional characteristic resulting from
      negative beliefs about uncertainty and its implications - may be an important
      construct in anxiety disorders and depression. Despite the potential importance
      of IU, clinical data on the construct remains relatively scant and focused on
      generalized anxiety disorder and obsessive-compulsive disorder. The present study
      systematically investigated IU, as measured by the Intolerance of Uncertainty
      Scale-12 (IUS-12), across groups diagnosed with anxiety disorders (i.e., social
      anxiety disorder, panic disorder, generalized anxiety disorder, obsessive
      compulsive disorder) or depression (clinical sample: n=376; 61% women), as well
      as undergraduate (n=428; 76% women) and community samples (n=571; 67% women).
      Analysis of variance revealed only one statistically significant difference in
      IUS-12 scores across diagnostic groups in the clinical sample; specifically,
      people with social anxiety disorder reported higher scores (p<.01; eta(2)=.03)
      than people with panic disorder. People diagnosed with an anxiety disorder or
      depression reported significantly and substantially higher IUS-12 scores relative
      to community and undergraduate samples. Furthermore, IUS-12 score distributions
      were similar across diagnostic groups as demonstrated by Kernel density
      estimations, with the exception of panic disorder, which may have a relatively
      flat distribution of IU. Response patterns were invariant across diagnostic
      groups as demonstrated by multi-group confirmatory factor analyses, but varied
      between clinical and nonclinical samples. Overall, the findings suggest IU may
      serve as an important transdiagnostic feature across anxiety disorders and
      depression. In addition, robust support was found for the proposed 2-factor model
      of the IUS-12. Comprehensive findings, implications, and future research
      directions are discussed.

PMID- 22366535
TI  - Effects of subthalamic nucleus deep brain stimulation and L-DOPA on blinking in
      Parkinson's disease.
AB  - In this study we asked whether subthalamic nucleus deep brain stimulation (STN
      DBS) alone, or in combination with l-dopa, modifies voluntary, spontaneous and
      reflex blinking in patients with Parkinson's disease (PD). Sixteen PD patients
      who underwent STN-DBS were studied in four experimental conditions: without STN
      DBS and without l-dopa, STN-DBS alone, l-dopa alone and STN-DBS plus l-dopa. The
      results were compared with those obtained in 15 healthy controls. Voluntary
      blinking was assessed by asking participants to blink as fast as possible;
      spontaneous blinking was recorded during two 60s rest periods; reflex blinking
      was evoked by electrical stimulation of the supraorbital nerve. Blinking were
      recorded and analysed with the SMART motion system. STN-DBS increased the peak
      velocity and amplitude for both the closing and opening voluntary blink phases,
      but prolonged the inter-phase pause duration. l-dopa had no effects on voluntary
      blinking but reversed the increased inter-phase pause duration seen during STN
      DBS. Spontaneous blink rate increased after either STN-DBS or l-dopa. Reflex
      blinking kinematics were not modified by STN-DBS or l-dopa. The STN-DBS effects
      on voluntary blinking kinematics and spontaneous blinking rate may occur as
      results of changes of cortico-basal ganglia activity. The prolonged pause
      duration of voluntary blinking indicates that STN-DBS has detrimental effects on
      the cranial region. These results also shed light on the pathophysiology of
      eyelids opening apraxia following STN-DBS.

PMID- 22366537
TI  - Reconstruction of a maxillary defect using the remnant bone of mandibular angle
      ostectomy.
AB  - The buttress is the cornerstone of the midface both functionally and
      aesthetically. Therefore, fracture of the buttress requires surgery. A patient
      wanted cosmetic surgery simultaneously with a reduction of facial bone fracture.
      To achieve this, we reconstructed the defect of the maxillary buttress using the
      remnant bone of the mandible angle ostectomy. A 27-year-old man presented with a
      left maxilla fracture and defect at the maxillary buttress. Since the patient was
      considering cosmetic surgery to alter his square face, we planned a mandibular
      angle ostectomy and used the remnant bone as an onlay bone graft for maxillary
      reconstruction. There was no complication and the patient was satisfied with both
      the functional and aesthetical look of the reconstructive surgery. We
      reconstructed the defect of the maxillary buttress successfully using the remnant
      bone of the mandible angle ostectomy. Although this technique cannot be applied
      to every patient, reconstruction of facial bone defects with the remnant bone of
      the mandibular angle ostectomy may be a potential option in some cases.

PMID- 22366536
TI  - The use of a chimaeric sero-muscular flap to prevent anastomotic leakage in head
      and neck reconstruction with free ileocolon flap.
AB  - BACKGROUND: In simultaneous reconstructions of cervical oesophagus and voice
      mechanism with free ileocolon flap, one of the most cumbersome complications is
      the anastomotic leakage at the junction between the colon and thoracic
      oesophagus. METHODS: Since 2007, a chimaeric sero-muscular flap has been islanded
      from the distal end of the voice tube to cover the anterior aspect of the colo
      oesophageal junction. Fourteen patients undergoing reconstruction of the
      hypopharyngo-laryngectomy defects were consecutively treated with the sero
      muscular flap. The leakage rate was compared with a group of 15 patients who were
      reconstructed with a free ileocolon flap prior to the adoption of the new
      procedure. RESULTS: All flaps survived completely. Swallowing function (scores 5
      7), was restored in 69% of the patients. Speech function was restored (scores 4
      5) in 59% of the patients. In the treatment group, only one patient suffered from
      anastomotic leakage compared to four patients in the control group. CONCLUSIONS:
      The chimaeric sero-muscular flap can secure the colo-oesophageal junction,
      improving the healing process and preventing delays in the administration of
      adjuvant therapy.

PMID- 22366538
TI  - Comparison of reinnervation for preservation of denervated muscle volume with
      motor and sensory nerve: an experimental study.
AB  - Prevention of the atrophy of denervated muscles is essential for a good outcome
      in facial contouring and oral reconstruction. In this study, we compared the
      effectiveness of end-to-end and end-to-side neurorrhaphy of the motor nerve, and
      end-to-end neurorrhaphy of the sensory nerve, all of which are frequently used in
      such reconstruction for the prevention of muscle atrophy. Wistar rats were
      divided into four groups: group 1, motor nerve division of semi-membranosus
      without repair; group 2, motor nerve division and end-to-end coaptation to the
      saphenous nerve; group 3, motor nerve division and end-to-side coaptation to the
      sciatic nerve; and group 4, motor nerve division and end-to-end repair.
      Measurement of semi-membranosus volume, histological evaluation and staining of
      neuromuscular junctions that were carried out 3 months postoperatively revealed
      that muscle volume preservation was larger in groups 3 and 4 than in the other
      two groups (p<0.05), but slightly superior in group 4 (p<0.05). There was no
      statistical difference between groups 2 and 1; histologically, muscle
      architecture was better preserved in group 2 than in group 1; reactivation of the
      neuromuscular junctions was observed in all except group 1. End-to-side repair of
      motor nerves is one of the better options for the preservation of muscle volume
      when end-to-end nerve repair is not indicated. Sensory protection may also
      provide some advantages in the preservation of muscle volume.

PMID- 22366539
TI  - The nerve to delay: the impact of delayed referrals in the management of
      traumatic brachial plexus injuries in the Republic of Ireland.

PMID- 22366540
TI  - "Sea anemone-shaped fixation": a feasible tie-over technique for axillary
      osmidrosis.

PMID- 22366541
TI  - Dyslipidaemia and age-related involutional blepharoptosis.
AB  - BACKGROUND: The aetiology of age-related involutional blepharoptosis may be
      multifactorial. Dyslipidaemia may be involved in the pathogenesis of this
      disease, as dyslipidaemia, which is often related to ageing, is a risk factor for
      many disorders. The relationship between lipid profiles and age-related
      involutional blepharoptosis was evaluated to investigate this hypothesis. There
      are no known reference data in the literature examining the statistical
      association between dyslipidaemia and age-related involutional blepharoptosis.
      METHODS: The study population was 251 consecutive Japanese patients aged 60 years
      or older who had at least one of the most common age-related changes of the
      eyelid and eyebrow, and who underwent surgical intervention. Blepharoptosis was
      defined as a marginal reflex distance of <2mm. Using strict exclusion criteria
      applied to all the patients regardless of eyelid position, 101 patients were
      finally enrolled. The selected demographic and clinical characteristics, as well
      as biochemical parameters including plasma lipids, were statistically compared
      between the patients who developed pure age-related involutional blepharoptosis
      and those who did not. MAIN FINDINGS: Dyslipidaemia was observed to be associated
      with the presence of age-related involutional blepharoptosis (odds ratio: 4.008,
      95% confidence interval: 1.586-10.131, p=0.002). Univariate analysis revealed
      that triglycerides and non-high-density lipoprotein cholesterol were
      significantly higher in patients with age-related involutional blepharoptosis
      compared with those without blepharoptosis. With multivariate analysis, non-high
      density lipoprotein cholesterol (p=0.003) and high-density lipoprotein
      cholesterol (p=0.044) were both significantly and independently associated with
      the presence of age-related involutional blepharoptosis, but in opposite
      directions (positive and inverse, respectively), whereas triglycerides were no
      longer significant. CONCLUSION: Dyslipidaemia, specifically atherogenic
      dyslipidaemia, should be considered as a possible determinant of age-related
      involutional blepharoptosis. Further studies are required to clarify the causal
      relationship between dyslipidaemia and age-related involutional blepharoptosis.

PMID- 22366542
TI  - Mechanisms of activation and survival of ovarian follicles.

PMID- 22366543
TI  - Impact of epigallo catechin-3-gallate on acetylcholine-acetylcholine esterase
      cycle in aged rat brain.
AB  - Neurotransmission plays an important role in communication of messages in brain.
      Cholinergic alterations during aging are associated with learning and memory.
      Neurotransmitters and enzymes that influence these neurotransmitters are
      significant in age-associated memory. Neurotransmitters like acetylcholine,
      serotonin and dopamine levels were studied. Kinetics of acetylcholine esterase
      was studied. There was an alteration in km and Vm values which was brought back
      to near-normalcy by EGCG. Behavioural changes were assessed by radial maze
      experiment. EGCG, a good neuroprotective drug proved to alleviate the behavioural
      alterations in aged rat brain. Acetylcholine esterase was partially purified from
      rat brain and assayed in vitro. Several modifiers like EGCG and donepezil were
      added in silico and the activity of the enzyme was calculated. EGCG increased the
      activity when compared to negative control, donepezil. Using bioinformatics tools
      EGCG, acetylcholine and donepezil were docked with acetylcholine esterase. EGCG
      formed a good docking-complex with the enzyme. Thus, it shall be hypothesized
      that the neuroprotective activity of EGCG might be due to its influence on
      cholinergic neurotransmission thereby improving the cognitive functions of the
      brain.

PMID- 22366544
TI  - Structural basis for profilin-mediated actin nucleotide exchange.
AB  - Actin is a ubiquitous eukaryotic protein that is responsible for cellular
      scaffolding, motility, and division. The ability of actin to form a helical
      filament is the driving force behind these cellular activities. Formation of a
      filament depends on the successful exchange of actin's ADP for ATP. Mammalian
      profilin is a small actin binding protein that catalyzes the exchange of
      nucleotide and facilitates the addition of an actin monomer to a growing
      filament. Here, crystal structures of profilin-actin have been determined to show
      an actively exchanging ATP. Structural analysis shows how the binding of profilin
      to the barbed end of actin causes a rotation of the small domain relative to the
      large domain. This conformational change is propagated to the ATP site and causes
      a shift in nucleotide loops, which in turn causes a repositioning of Ca(2+) to
      its canonical position as the cleft closes around ATP. Reversal of the solvent
      exposure of Trp356 is also involved in cleft closure. In addition, secondary
      calcium binding sites were identified.

PMID- 22366545
TI  - Impact of ligand and protein desolvation on ligand binding to the S1 pocket of
      thrombin.
AB  - In the present study, we investigate the impact of a tightly bound water molecule
      on ligand binding in the S1 pocket of thrombin. The S1 pocket contains a deeply
      buried deprotonated aspartate residue (Asp189) that is, due to its charged state,
      well hydrated in the uncomplexed state. We systematically studied the importance
      of this water molecule by evaluating a series of ligands that contains pyridine
      type P1 side chains that could potentially alter the binding properties of this
      water molecule. All of the pyridine derivatives retain the original hydration
      state albeit sometimes with a slight perturbance. In order to prevent a direct H
      bond formation with Asp189, and to create a permanent positive charge on the P1
      side chain that is positioned adjacent to the Asp189 carboxylate anion, we
      methylated the pyridine nitrogen. This methylation resulted in displacement of
      water but was accompanied by a loss in binding affinity. Quantum chemical
      calculations of the ligand solvation free energy showed that the positively
      charged methylpyridinium derivatives suffer a large penalty of desolvation upon
      binding. Consequently, they have a substantially less favorable enthalpy of
      binding. In addition to the ligand desolvation penalty, the hydration shell
      around Asp189 has to be overcome, which is achieved in nearly all pyridinium
      derivatives. Only for the ortho derivative is a partial population of a water
      next to Asp189 found. Possibly, the gain of electrostatic interactions between
      the charged P1 side chain and Asp189 helps to compensate for the desolvation
      penalty. In all uncharged pyridine derivatives, the solvation shell remains next
      to Asp189, partly mediating interactions between ligand and protein. In the case
      of the para-pyridine derivative, a strongly disordered cluster of water sites is
      observed between ligand and Asp189.

PMID- 22366546
TI  - Drug eluting stents: developments and current status.
AB  - Coronary stenting has revolutionized current perspective of coronary artery
      disease management. Bare-metal stents (BMS) were introduced in 1994, but long
      term results have been shattered by the dual problems of in-stent restenosis
      (ISR) and stent thrombosis associated with BMS. Though stent thrombosis became
      much less frequent after the introduction of antiplatelet therapy, restenosis
      however remained as a significant problem. Intense work on stent development has
      successfully led to the introduction of drug-eluting stents (DES) in 2002, as an
      effort to address restenosis problem. First generation DES (sirolimus and
      paclitaxel eluting) were introduced first and found to be more effective than
      BMS. The use of first generation DES dealt with the problem of restenosis. But,
      despite early successes, uncertainty remains on the overall safety, especially
      for late adverse clinical events such as stent thrombosis. Thus, the second
      generation (everolimus and zotarolimus eluting) stents were developed and
      introduced with lower thrombosis rates. Today, in the search for improving the
      performance of available DES various developments and clinical studies are
      ongoing. Research and developments is primarily centred on increasing the long
      term safety and efficacy of stents.

PMID- 22366547
TI  - Polymer coatings for delivery of nucleic acid therapeutics.
AB  - Gene delivery remains the greatest challenge in applying nucleic acid therapeutic
      for a broad range of diseases. Combining stability during the delivery phase with
      activation and transgene expression following arrival at the target site requires
      sophisticated vectors that can discriminate between cell types and respond to
      target-associated conditions to trigger expression. Efficient intravenous
      delivery is the greatest single hurdle, with synthetic vectors frequently found
      to be unstable in the harsh conditions of the bloodstream, and viral vectors
      often recognized avidly by both the innate and the adaptive immune system. Both
      types of vectors benefit from coating with hydrophilic polymers. Self-assembling
      polyelectrolyte non-viral vectors can achieve both steric and lateral
      stabilization following surface coating, endowing them with much improved
      systemic circulation properties and better access to disseminated targets;
      similarly viral vectors can be 'stealthed' and their physical properties
      modulated by surface coating. Both types of vectors may also have their tropism
      changed following chemical linkage of novel ligands to the polymer coating. These
      families of vectors go some way towards realizing the goal of efficient systemic
      delivery of genes and should find a range of important uses in bringing this
      still-emerging field to fruition.

PMID- 22366548
TI  - Epigenetics: a key regulator of platyhelminth developmental biology?
AB  - The Platyhelminthes (flukes/flatworms) are a large group of derived metazoans
      beautifully adapted for existence in diversely challenging ecosystems. As
      tractable examples of development and self-regeneration or as causative agents of
      aquacultural, veterinary and biomedically-relevant parasitic diseases, the
      platyhelminths are subject to intensive inter-disciplinary research. Given the
      complex lifestyles exhibited by individuals within this phylum, we postulate that
      epigenetic processes feature in many aspects of platyhelminth lifecycle
      diversity, development and environmentally-driven adaptations.

PMID- 22366549
TI  - The impaired pregnancy outcome in murine congenital toxoplasmosis is associated
      with a pro-inflammatory immune response, but not correlated with decidual
      inducible nitric oxide synthase expression.
AB  - Congenital toxoplasmosis is associated with adverse pregnancy outcome. Despite
      the type 1 immune response, C57BL/6 mice are more susceptible than BALB/c mice to
      Toxoplasma gondii infection. Additionally, successful pregnancy appears to be
      correlated with type 2 T helper maternal immunity and regulatory T cells. In
      order to investigate the mechanisms of susceptibility/resistance to congenital
      toxoplasmosis in mice with different genetic backgrounds and the influence of
      inducible nitric oxide synthase in pregnancy outcome, groups of C57BL/6, BALB/c
      and C57BL/6 iNOS(-/-) females were orally infected with T. gondii ME-49 strain on
      day 1 of pregnancy and were sacrificed on day 8 p.i. and day 19 p.i. The uterus
      and placenta were evaluated for the foetal resorption rate, parasite load,
      immunological and histological changes. C57BL/6 mice presented inflammatory foci
      in the decidua (endometrium) of the uterus at a higher frequency than BALB/c mice
      on day 8 p.i., and a large number of pregnant C57BL/6 mice presented necrotic
      implantation sites. The parasite was seldom found in the uterus or placenta of
      either lineage of mice. Interestingly, there was no observed difference in
      inducible nitric oxide synthase expression in the uterus and placenta of infected
      mice. In addition, higher levels of TNF-alpha were detected in serum samples from
      C57BL/6 mice compared with BALB/c mice. Accordingly, C57BL/6 mice presented with
      levels of 90% abortion compared with 50% in BALB/c mice on day 19 p.i. C57BL/6
      iNOS(-/-) mice showed low placental parasite counts and high absorption rates,
      similar to wild type mice. The data suggest that the impaired pregnancy outcome
      due to T. gondii infection in C57BL/6 mice could be associated with a higher
      inflammatory response leading to cell apoptosis and necrosis of implantation
      sites compared with BALB/c mice, and this phenomenon was not due to inducible
      nitric oxide synthase expression in the decidua.

PMID- 22366551
TI  - Characterization of a beta-D-mannosidase from a marine gastropod, Aplysia
      kurodai.
AB  - A beta-D-mannosidase (EC 3.2.1.25) with a molecular mass of approximately 100 kDa
      was purified from the digestive fluid of a marine gastropod Aplysia kurodai by
      ammonium sulfate fractionation followed by column chromatographies on TOYOPEARL
      Butyl-650 M, TOYOPEARL DEAE-650 M, and Superdex 200 10/300 GL. This enzyme, named
      AkMnsd in the present study, showed optimal activities at pH 4.5 and 40  degrees
      C and was stable at the acidic pH range from 2.0 to 6.7 and the temperature below
      38  degrees C. The Km and Vmax values for AkMnsd determined at pH 6.0 and 30 
      degrees C with p-nitrophenyl beta-d-mannopyranoside were 0.10 mM and 3.75
      MUmol/min/mg, respectively. AkMnsd degraded various polymer mannans as well as
      mannooligosaccharides liberating mannose as a major degradation product. Linear
      mannan from green alga Codium fragile was completely depolymerized by AkMnsd in
      the presence of AkMan, an endolytic beta-mannanase, which we previously isolated
      from the same animal (Zahura et al., Comp. Biochem. Physiol. B 157, 137-148
      (2010)). A cDNA encoding AkMnsd was amplified from the Aplysia hepatopancreas
      cDNA by the PCR using degenerated primers designed on the basis of N-terminal and
      internal amino-acid sequences of AkMnsd. The cloned AkMnsd cDNA consisted of 2985
      bp and encoded an amino-acid sequence of 931 residues with the calculated
      molecular mass of 101,970 Da. The deduced sequence of AkMnsd showed 20-43% amino
      acid identity to those of glycoside-hydrolase-family 2 (GHF2) beta-mannosidases.
      The catalytically important amino-acid residues determined in GHF2 enzymes were
      completely conserved in AkMnsd. Thus, AkMnsd is regarded as a new member of GHF2
      mannosidase from marine gastropod.

PMID- 22366550
TI  - Trichostrongylus colubriformis larvae induce necrosis and release of IL33 from
      intestinal epithelial cells in vitro: implications for gastrointestinal nematode
      vaccine design.
AB  - Gastrointestinal nematodes represent a major production problem for ruminant
      livestock. Enhancing immunity to gastrointestinal nematodes through vaccination
      is desirable but mechanistic understanding of initial host responses that
      facilitate gastrointestinal nematode protective immunity is limited. We
      hypothesise that gastrointestinal nematode invasion induces mucosal epithelium
      damage and alarmin (e.g. IL33) release, thereby contributing to initiation of
      protective gastrointestinal nematode immunity. To test this, an in vitro air
      liquid interface human HT-29 epithelial cell-Trichostrongylus colubriformis co
      culture system was developed. Exsheathed L3 T. colubriformis exhibited both
      sinusoidal and burrowing motions in the co-culture system. Burrowing parasites,
      but not ivermectin-paralysed larvae, induced necrotic death of epithelial cells
      (annexin V(+)/propidium iodide(+)/caspase 3/7(-)). Microscopy confirmed that
      larvae consumed labelled necrotic epithelial cell contents. Trichostrongylus
      colubriformis larvae and their post-exsheathment antigens (excretory/secretory
      products) significantly induced IL33 mRNA expression in the epithelial cells.
      Immunoblot confirmed that IL33 was released from epithelial cells due to the
      damage caused by motile larvae. Exposure of HT-29 cells to alum or Sigma
      proprietary adjuvants induced significant epithelial cell IL33 mRNA expression
      without inducing cellular necrosis. Hence, the intracellular contents were not
      released externally where they might exert alarmin activity and this may limit
      their ability to trigger a protective anti-gastrointestinal nematode response. We
      conclude that T. colubriformis motion at the infection site induces intestinal
      epithelial cell necrosis which facilitates the release of intracellular contents,
      including IL33, and may be fundamental to the initiation of an appropriate host
      response to gastrointestinal nematodes. Our co-culture model is useful for
      studying initial epithelial cell-parasite interactions without conducting
      expensive animal trials.

PMID- 22366552
TI  - A goose-type lysozyme gene in Japanese scallop (Mizuhopecten yessoensis): cDNA
      cloning, mRNA expression and promoter sequence analysis.
AB  - Lysozyme is an important component of the immune response against bacteria that
      is characterized by its ability to break down bacterial cell-walls. We
      constructed a high-quality cDNA library from mantle tissue of adult Japanese
      scallop (Mizuhopecten yessoensis). The EST which is high homology with g-type
      lysozyme genes of other species was found in the cDNA library. In the present
      study, the complete express sequence of g-type lysozyme genes from Japanese
      scallop (designated as MyLysoG) was directly obtained by PCR. The complete
      sequence of MyLysoG cDNA consisted of a 5' untranslated region (UTR) of 25 bp, an
      open reading frame (ORF) of 606 bp, and a 3' UTR of 100 bp with one
      polyadenylation signal (AATAAA). The deduced amino acids of MyLysoG were 201
      amino acids with a putative signal peptide of 18 amino acid residues. It shared
      the sequence similarity and the common structure features with the g-type
      lysozyme from other species. Quantitative reverse trancriptase real-time PCR (qRT
      PCR) assay demonstrated that mRNA transcripts of g-type lysozyme could be
      detected in various tissues of unchallenged scallop, and the highest expression
      of MyLysoG was detected in hepatopancreas tissue. The temporal expression of
      MyLysoG in hemolymph after Vibrio anguillarum challenge was up-regulated and
      reached the maximum level at 3h post stimulation, and then dropped back to the
      original level even lower than the control group. Furthermore, a 978 bp of 5'
      flanking sequence of MyLysoG was identified by genome walking, and several
      potential transcription factor binding sites (TFBS) were detected in the putative
      promoter region. One part of the MyLysoG promoter region contains nine sites of
      SNPs and three sites of insert-deletion (indel) polymorphisms, and these
      mutations were found organize into two haplotypes. The two haplotypes were
      associated with different TFBS. The haplotypes could be selected to analyze the
      transcriptional-level control of scallop g-type lysozyme gene and the scallop
      immune system.

PMID- 22366553
TI  - Acylated flavonol glycosides from Epimedium elatum, a plant endemic to the
      Western Himalayas.
AB  - Herba Epimedii is a well-known Botanical preparation used over long time in
      traditional Chinese medicine. The extracts and chemical constituents from
      Epimedium species are aphrodisiac as well as to treat many ailments. Chemical
      investigation of lonely species growing in Kashmir Himalaya Epimedium elatum was
      undertaken to evaluate its chemical profile. Two unusual substituted acylated
      flavonol glycosides named Elatoside A (1) and Elatoside B (2) have been isolated
      from the ethanolic extract of E. elatum along with 23 previously known ones (3
      25). All isolates were evaluated for antimicrobial and PPAR-gamma ligand binding
      activity, and some of them appeared to be modestly active.

PMID- 22366554
TI  - In situ metabolomic mass spectrometry imaging: recent advances and difficulties.
AB  - MS imaging (MSI) is a remarkable new technology that enables us to determine the
      distribution of biological molecules present in tissue sections by direct
      ionization and detection. This technique is now widely used for in situ imaging
      of endogenous or exogenous molecules such as proteins, lipids, drugs and their
      metabolites, and it is a potential tool for pathological analysis and the
      investigation of disease mechanisms. MSI is also thought to be a technique that
      could be used for biomarker discovery with spatial information. The application
      of MSI to the study of endogenous metabolites has received considerable attention
      because metabolites are the result of the interactions of a system's genome with
      its environment and a total set of these metabolites more closely represents the
      phenotype of an organism under a given set of conditions. Recent studies have
      suggested the importance of in situ metabolite imaging in biological discovery
      and biomedical applications, but several issues regarding the technical
      application limits of MSI still remained to be resolved. In this review, we
      describe the capabilities of the latest MSI techniques for the imaging of
      endogenous metabolites in biological samples, and also discuss the technical
      problems and new challenges that need to be addressed for effective and
      widespread application of MSI in both preclinical and clinical settings.

PMID- 22366555
TI  - Biotechnological advances in the diagnosis, species differentiation and
      phylogenetic analysis of Schistosoma spp.
AB  - Schistosomiasis is a serious parasitic disease caused by blood-dwelling flukes of
      the genus Schistosoma. Throughout the world, schistosomiasis is associated with
      high rates of morbidity and mortality, with close to 800 million people at risk
      of infection. Precise methods for identification of Schistosoma species and
      diagnosis of schistosomiasis are crucial for an enhanced understanding of
      parasite epidemiology that informs effective antiparasitic treatment and
      preventive measures. Traditional approaches for the diagnosis of schistosomiasis
      include etiological, immunological and imaging techniques. Diagnosis of
      schistosomiasis has been revolutionized by the advent of new molecular
      technologies to amplify parasite nucleic acids. Among these, polymerase chain
      reaction-based methods have been useful in the analysis of genetic variation
      among Schistosoma spp. Mass spectrometry is now extending the range of biological
      molecules that can be detected. In this review, we summarize traditional, non-DNA
      based diagnostic methods and then describe and discuss the current and developing
      molecular techniques for the diagnosis, species differentiation and phylogenetic
      analysis of Schistosoma spp. These exciting techniques provide foundations for
      further development of more effective and precise approaches to differentiate
      schistosomes and diagnose schistosomiasis in the clinic, and also have important
      implication for exploring novel measures to control schistosomiasis in the near
      future.

PMID- 22366556
TI  - Involvement of dopaminergic and serotonergic systems in the neurobehavioral
      toxicity of lambda-cyhalothrin in developing rats.
AB  - In view of extensive uses of lambda-cyhalothrin, a new generation type II
      synthetic pyrethroid, human exposure is quite imminent. The present study has
      therefore been carried out to investigate effect of lambda-cyhalothrin on brain
      dopaminergic and serotonergic systems and functional alterations associated with
      them. Post-lactational exposure to lambda-cyhalothrin (1.0 mg/kg or 3.0 mg/kg
      body weight, p.o.) from PD22 to PD49 caused a significant decrease in the motor
      activity and rota-rod performance in rats on PD50 as compared to controls.
      Decrease in motor activity in lambda-cyhalothrin treated rats was found to
      persist 15 days after withdrawal of exposure on PD65 while a trend of recovery in
      rota-rod performance was observed. A decrease in the binding of 3H-Spiperone,
      known to label dopamine-D2 receptors in corpus striatum associated with decreased
      expression of tyrosine hydroxylase (TH)-immunoreactivity and TH protein was
      observed in lambda-cyhalothrin treated rats on PD50 and PD65 compared to
      controls. Increase in the binding of 3H-Ketanserin, known to label serotonin-2A
      receptors in frontal cortex was observed in lambda-cyhalothrin exposed rats on
      PD50 and PD65 as compared to respective controls. The changes were more marked in
      rats exposed to lambda-cyhalothrin at a higher dose (3.0 mg/kg) and persisted
      even 15 days after withdrawal of exposure. The results exhibit vulnerability of
      developing rats to lambda-cyhalothrin and suggest that striatal dopaminergic
      system is a target of lambda-cyhalothrin. Involvement of serotonin-2A receptors
      in the neurotoxicity of lambda-cyhalothrin is also suggested. The results further
      indicate that neurobehavioral changes may be more intense in case exposure to
      lambda-cyhalothrin continues.

PMID- 22366557
TI  - Low-dose, prospective triggered high-pitch spiral coronary computed tomography
      angiography: comparison with retrospective spiral technique.
AB  - RATIONALE AND OBJECTIVES: Cardiac computed tomographic angiography algorithms
      emphasize radiation reduction while maintaining diagnostic image quality (IQ).
      The aim of this study was to evaluate IQ and interreader variability using
      prospective electrocardiographically triggered high-pitch spiral cardiac computed
      tomographic angiography (FLASH-CT) compared to retrospective electrocardiographic
      gating (RETRO-CT) for coronary artery disease evaluation in a patient population
      including overweight and obese individuals. MATERIALS AND METHODS: Seventy
      patients (24 women; mean age, 60 years) matched for gender, age, body mass index
      (27.4 +/- 5.5 kg/m(2)), and calcium score (184 +/- 328) underwent cardiac
      computed tomographic angiography, 35 with FLASH-CT (Definition Flash) and 35 with
      RETRO-CT (Somatom Definition). Images were reconstructed using standard protocols
      and least motion phase for RETRO-CT acquisitions. Two independent, blinded
      readers evaluated the coronary arteries using an 18-segment model, grading IQ on
      a 5-point, Likert-type scale and coronary stenosis on a 5-point semiquantitative
      and binary scale. RESULTS: Effective radiation dose (1.50 vs 17.3 mSv, P < .0001)
      and mean heart rate (58 vs 62 beats/min, P < .05) were significantly lower for
      FLASH-CT compared to RETRO-CT. Seven hundred forty segments (> 1.5 mm) were
      evaluated. There was no significant difference between FLASH-CT and RETRO-CT
      scans in overall per-segment IQ (3.11 +/- 0.75 vs 3.10 +/- 0.82, P = .94). FLASH
      CT had noninferior IQ relative to RETRO-CT (95% confidence interval, -0.25 to
      0.26). There was no significant difference in interreader variability in
      diagnosis between FLASH-CT and RETRO-CT for all coronary segments (77.5% vs
      78.2%, P = .83). CONCLUSIONS: FLASH-CT is an acceptable coronary computed
      tomographic angiographic method for reducing radiation dose without compromising
      IQ for a patient population including overweight and obese individuals.

PMID- 22366558
TI  - Transitioning to a new residency curriculum.

PMID- 22366559
TI  - Gallbladder patterns in acute pancreatitis: an MRI study.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to assess the gallbladder
      patterns on magnetic resonance imaging (MRI) associated with acute pancreatitis
      (AP). MATERIALS AND METHODS: There were 197 patients with AP, all of whom had
      undergone abdominal MRI. AP was categorized as either edematous or necrotizing
      according to its findings on MRI and graded as mild (0-3 points), moderate (4-6
      points), or severe (7-10 points) according to the magnetic resonance severity
      index. The changes to the walls and dimensions of the gallbladder and common bile
      duct, in addition to the presence of biliary stones and pericholecystic fluid,
      were noted and compared with the severity of AP on the basis of the magnetic
      resonance severity index. RESULTS: Of the 197 patients with AP, 81% were
      classified as edematous and 19% as necrotizing on MRI. There were 35%, 59%, and
      6% of patients with mild, moderate, and severe AP according to the magnetic
      resonance severity index, respectively. Seventy-six percent of patients had at
      least one gallbladder abnormality on MRI, including a thickened gallbladder wall
      (42%), pericholecystic fluid (38%), gallbladder stones (35%), an enlarged
      gallbladder (24%), dilatation of the common bile duct (16%), and subserosal edema
      (15%). Eighty-nine percent of patients (34 of 38) with necrotizing AP had
      gallbladder abnormalities, which was significantly higher than the 72% of
      patients (115 of 159) with edematous AP (P < .05). The prevalence of gallbladder
      abnormalities was 64% in patients with mild AP, 81% in those with moderate AP,
      and 91% in those with severe AP (P < .05 among the three groups). CONCLUSIONS:
      Most patients with AP have gallbladder abnormalities on MRI, including a
      thickened gallbladder wall and pericholecystic fluid. The prevalence of
      gallbladder abnormalities has a positive correlation with the severity of AP on
      MRI.

PMID- 22366560
TI  - Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth.
AB  - Genomic aberrations of key regulators of the apoptotic pathway have hardly been
      identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the
      majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue
      Micro Array analysis. This BCL2 mRNA expression is strongly elevated compared to
      normal tissues and other malignancies. Most neuroblastoma cell lines lack this
      high BCL2 expression. Only two neuroblastoma cell lines (KCNR and SJNB12) show
      BCL2 expression levels representative for neuroblastoma tumours. To validate BCL2
      as a therapeutic target in neuroblastoma we employed lentivirally mediated shRNA.
      Silencing of BCL2 in KCNR and SJNB12 resulted in massive apoptosis, while cell
      lines with low BCL2 expression were insensitive. Identical results were obtained
      by treatment of the neuroblastoma cell lines with the small molecule BCL2
      inhibitor ABT263, which is currently being clinically evaluated. Combination
      assays of ABT263 with most classical cytostatics showed strong synergistic
      responses. Subcutaneous xenografts of a neuroblastoma cell line with high BCL2
      expression in NMRI nu/nu mice showed a strong response to ABT263. These findings
      establish BCL2 as a promising drug target in neuroblastoma and warrant further
      evaluation of ABT263 and other BCL2 inhibiting drugs.

PMID- 22366561
TI  - Adjuvant! Online is overoptimistic in predicting survival of Asian breast cancer
      patients.
AB  - BACKGROUND: Adjuvant! Online is a free web-based tool which predicts 10-year
      breast cancer outcomes and the efficacy of adjuvant therapy in patients with
      breast cancer. As its prognostic performance has only been validated in high
      income Caucasian populations, we validated the model in a middle income Asian
      setting. METHODS: Within the University Malaya Hospital-Based Breast Cancer
      Registry, all 631 women who were surgically treated for invasive non-metastatic
      breast cancer between 1993 and 2000 were identified. The discriminative
      performance of Adjuvant! Online was tested using receiver operating
      characteristic (ROC) analysis. Calibration of the model was evaluated by
      comparing predicted 10-year overall survival with observed 10-year survival.
      FINDINGS: Adjuvant! Online was fairly capable in discriminating between good and
      poor survivors, as attested by the area under ROC curve of 0.73 (95% Confidence
      Interval: 0.69-0.77). Overall, Adjuvant! Online predicted 10 year survival
      (70.3%) was significantly higher than the observed 10 year survival (63.6%,
      difference of 6.7%; 95% CI: 3.0-10.4%). The model was especially overoptimistic
      in women under 40 years and in women of Malay ethnicity, where survival was
      overestimated by approximately 20% (95% CI: 9.8-29.8%) and 15% (95% CI: 5.3
      24.5%) respectively. INTERPRETATION: Even though Adjuvant! Online is capable of
      discriminating between good and poor survivors, it systematically overestimates
      survival. These findings suggest that the model requires adaptation prior to use
      in Asian settings.

PMID- 22366562
TI  - Telomere length and regulatory proteins in human skeletal muscle with and without
      ongoing regenerative cycles.
AB  - New insights suggest the existence of telomere regulatory mechanisms in several
      adult tissues. In this study, we aimed to assess in vivo telomere length and the
      presence of specific proteins involved in telomere regulation in a model of human
      skeletal muscle with (patients with dermatomyosis or polymyositis) and without
      ongoing regenerative events (healthy subjects). Mean (meanTRF) and minimal
      telomere (miniTRF) lengths and the expression of telomerase, tankyrase 1, TRF2
      (telomeric repeat binding factor 2) and POT1 (protection of telomeres 1) were
      investigated in skeletal muscle samples from 12 patients (MYO) and 13 healthy
      subjects (CON). There was no significant shortening of telomeres in skeletal
      muscle from patients compared with control subjects (MYO, meanTRF length 11.0 +/-
      1.8 kbp and miniTRF length 4.7 +/- 0.8 kbp; CON, meanTRF length 10.4 +/- 1.1 kbp
      and miniTRF length 4.6 +/- 0.5 kbp). Theoretically, telomere length can be
      controlled by endogenous mechanisms. Here, we show for the first time that
      expression levels of telomerase, tankyrase 1, TRF2 and POT1 were, respectively,
      six-, seven-, three- and fivefold higher in the nuclear fraction of skeletal
      muscle of MYO compared with CON (P < 0.05). This suggests the existence of
      endogenous mechanisms allowing for telomere regulation in skeletal muscle with
      ongoing cycles of degeneration and regeneration and a model where regulatory
      factors are possibly involved in the protection of skeletal muscle telomeres.

PMID- 22366563
TI  - Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve
      activities in rats.
AB  - Adenosine is the first drug of choice in the treatment of supraventricular
      arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA)
      have been investigated, no information is available on the effects on cardiac
      vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA
      and cardiovascular variables to intravenous bolus administration of adenosine. In
      34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic
      fibres were recorded together with ECG, arterial pressure and ventilation, before
      and after administration of three doses of adenosine (100, 500 and 1000 MUg kg(
      1)). The effects of adenosine were also assessed in isolated perfused hearts (n =
      5). Adenosine induced marked bradycardia and hypotension, associated with a
      significant dose-dependent increase in VNA (+204 +/- 56%, P < 0.01; +275 +/-
      120%, P < 0.01; and +372 +/- 78%, P < 0.01, for the three doses, respectively; n
      = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted
      the adenosine-induced bradycardia (-56.0 +/- 4.5%, P < 0.05; -86.2 +/- 10.5%, P <
      0.01; and -34.3 +/- 9.7%, P < 0.01, respectively). Likewise, adenosine-induced
      bradycardia was markedly less in isolated heart preparations. Previous
      barodenervation did not modify the effects of adenosine on VNA. On the SNA side,
      adenosine administration was associated with a dose-dependent biphasic response,
      including overactivation in the first few seconds followed by a later profound
      SNA reduction. Earliest sympathetic activation was abolished by barodenervation,
      while subsequent sympathetic withdrawal was affected neither by baro- nor by
      chemodenervation. This is the first demonstration that acute adenosine is able to
      activate cardiac VNA, possibly through a central action. This increase in vagal
      outflow could make an important contribution to the antiarrhythmic action of this
      substance.

PMID- 22366564
TI  - Time course of hydrogen peroxide-thioredoxin balance and its influence on the
      intracellular signalling in myocardial infarction.
AB  - We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations
      and their association with some prosurvival and pro-apoptotic proteins, during
      the transition from myocardial infarction (MI) to heart failure in rats. Male
      Wistar rats were divided into the following six groups: three sham-operated
      groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac
      function was analysed by echocardiography; the concentration of H(2)O(2) and the
      ratio of reduced to oxidized glutathione were measured spectrophotometrically,
      while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin
      II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and
      p-GSK3beta/GSK3beta was evaluated by Western blot. Our results show that
      thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2)
      concentration. It was associated with lower JNK expression in the early period
      post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin
      system markers and levels of H(2)O(2) increased, over 28 days post-MI, in
      parallel with some signalling proteins involved in maladaptative cardiac
      remodelling and ventricular dysfunction. These findings provide insight into the
      time course profile of endogenous antioxidant adaptation to ischaemic injury,
      which may be useful for the design of therapeutical strategies targeting
      oxidative stress post-MI.

PMID- 22366565
TI  - The pathophysiological basis of chronic hypoxic pulmonary hypertension in the
      mouse: vasoconstrictor and structural mechanisms contribute equally.
AB  - Chronic hypoxic pulmonary hypertension is characterized by a sustained increase
      in pulmonary arterial pressure due to abnormally elevated pulmonary vascular
      resistance. This increased vascular resistance was previously thought to be due
      largely to changes in the structure of the pulmonary vasculature, i.e. lumen
      narrowing due to wall hypertrophy and loss of vessels. Recently, this model has
      been challenged by the demonstration that hypoxic pulmonary hypertension in the
      rat is caused almost completely by sustained vasoconstriction. The contribution
      of this vasocontriction to hypoxic pulmonary hypertension has not been examined
      directly in other species. We exposed groups of mice to hypoxia (10% O(2)) or
      normoxia for 3 weeks, following which the lungs were removed post mortem, and
      vascular resistance was measured in an isolated, ventilated, perfused
      preparation. Mean pulmonary vascular resistance was significantly increased in
      hypoxic compared with control normoxic lungs. The rho kinase inhibitor Y27635
      (10(-4)m) (Tocris Bioscience, Bristol, United Kingdom.) significantly reduced the
      mean (+/- SEM) hypoxia induced increase by 45.4 (10.8)%, implying that structural
      vascular changes acounted for the remainder of the hypoxic increase.
      Stereological quantification showed a significant reduction in the mean lumen
      diameter of the fully relaxed vessels in hypoxic lungs compared with normoxic
      control lungs; there was no intra-acinar vessel loss. Thus, in contrast to the
      rat, hypoxic pulmonary hypertension in the mouse is due to two mechanisms
      contributing equally: sustained vasoconstriction and structural lumen narrowing
      of intra-acinar vessels. These important species diferences must be considered
      when using genetically mutated mice to investigate the mechanisms underlying
      pulmonary hypertension.

PMID- 22366566
TI  - Biochemical characterization of RNase HII from Aeropyrum pernix.
AB  - Aeropyrum pernix contains one homolog of ribonuclease H (RNase H), A. pernix
      RNase HII (Ape-RNase HII). Activity characterization showed that Ape-RNase HII
      exhibited the highest activity in the presence of 5 mM Mn(2+), 1 mM Co(2+), or 10
      mM Mg(2+), respectively; however, its cleavage efficiencies at different cleavage
      sites for Mn(2+) and Mg(2+) were different. Ape-RNase HII cleaved 12-bp RNA/DNA
      substrates at multiple sites and the optimum pH value was 11.0. Moreover, 16-bp
      DNA-r4-DNA/DNA and 13-bp DNA-r1-DNA/DNA chimeric substrates were cleaved at DNA
      RNA junction. Ape-RNase HII was thermostable and the stabilization was enhanced
      with increased salt concentration. This work is believed to be the first in vitro
      functional study of Ape-RNase HII and the results should contribute to the
      analysis of RNase H of other archaeal species.

PMID- 22366567
TI  - Mitral valve degeneration: still more questions than answers.

PMID- 22366568
TI  - Prediction of first onset of congestive heart failure in dogs with degenerative
      mitral valve disease: the PREDICT cohort study.
AB  - OBJECTIVE: To identify risk factors for first-onset congestive heart failure
      (CHF) in dogs with degenerative mitral valve disease (DMVD). ANIMALS: Eighty-two
      dogs with and without CHF secondary to DMVD were retrospectively assigned to a
      derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a
      prospective validation cohort. METHODS: Variables associated with risk of CHF in
      dogs were identified in a derivation cohort and used to construct a predictive
      model, which was then prospectively tested through longitudinal examination of a
      validation cohort. RESULTS: Logistic regression analysis of the derivation cohort
      yielded a predictive model that included the left atrial to aortic root dimension
      ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic
      peptide (NT-proBNP). When this model was prospectively applied to the validation
      cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of
      the validation cohort revealed that plasma NT-proBNP concentration and indexed
      left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors
      for development of first-onset CHF in dogs with DMVD (NT-proBNP >= 1500 pmol/L,
      odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37-24.28, P = 0.017;
      LVIDd:Ao >= 3, OR, 6.11, 95% CI, 1.09-34.05, P = 0.039). CONCLUSIONS: Measures of
      left heart size and plasma NT-proBNP concentration independently estimate risk of
      first-onset of CHF in dogs with DMVD. These parameters can contribute to the
      management of dogs with DMVD.

PMID- 22366569
TI  - Selected echocardiographic variables change more rapidly in dogs that die from
      myxomatous mitral valve disease.
AB  - OBJECTIVES: To determine if echocardiographic measurements change at a greater
      rate in dogs with myxomatous mitral valve disease (MMVD) that die of cardiac
      mortality. ANIMALS: Client-owned dogs (n = 242) with MMVD of varying severity
      were recruited from first opinion private practice. Only dogs which died during
      the study period (n = 102) were included in statistical analyses. METHODS:
      Prospective cohort study comparing the rate of change of echocardiographic
      variables between dogs that experienced cardiac mortality and those that
      experienced non-cardiac mortality. Measurements were repeated approximately every
      6 months and repeated measures linear models were constructed to estimate the
      rate of change of each variable over time. RESULTS: Left ventricular (LV) end
      diastolic diameter, normalized for body weight (LVEDDN) increased over time in
      both mortality groups. LV end-systolic diameter, normalized for body weight
      (LVESDN), LV end-diastolic diameter to LV free wall thickness in diastole
      (LVEDD/LVFWd) ratio, E wave velocity, E- to A-wave velocity ratio and left atrial
      to aortic root diameter ratio all increased over time in the cardiac mortality
      group, but did not change in the non-cardiac mortality group. MR velocity
      decreased over time in the cardiac mortality group but did not change in the non
      cardiac mortality group. Tricuspid regurgitation jet velocity increased over time
      in both mortality groups. A wave velocity and fractional shortening did not
      change over time in either mortality group. CONCLUSIONS: Serial echocardiographic
      examination every 6-12 months is useful to identify dogs with progressive MMVD
      that are at increased risk of cardiac mortality.

PMID- 22366570
TI  - Ultrasonographic measurement of flow-mediated vasodilation in dogs with chronic
      valvular disease.
AB  - OBJECTIVES: To measure flow-mediated vasodilation (FMD) in healthy dogs and in
      client-owned dogs with chronic valvular disease (CVD) and to investigate possible
      correlations between markers of CVD severity and FMD. ANIMALS: Twelve dogs with
      CVD and 11 healthy weight-matched dogs. METHODS: Brachial artery FMD following 5
      min inflation of a cuff around the antebrachium was measured in 12 dogs with CVD
      and 11 healthy weight-matched dogs. Measurements were also obtained in the
      healthy dogs 5 min after cuff placement but without inflation ('sham cuff
      placement'). Dogs with CVD underwent echocardiography to confirm and characterize
      their disease. RESULTS: In healthy dogs (median age 4 [2-6] years), median FMD
      was 7.7% versus 3.4% with sham cuff placement (P = 0.003). In dogs with CVD
      (median age 8 [4-16] years) median FMD was 5.5% versus 7.7% in healthy dogs (P =
      0.131). FMD showed an inverse correlation with left ventricular end-diastolic
      diameter normalized for body weight (r = -0.76, P = 0.0043). CONCLUSIONS:
      Brachial FMD in dogs with early CVD inversely correlates with severity of left
      ventricular remodelling.

PMID- 22366571
TI  - Mitral valve repair in dogs.
AB  - Prognosis for dogs with severe mitral regurgitation is poor with medical therapy
      alone. Open surgical mitral valve repair consisting of circumferential mitral
      annuloplasty and artificial chordal replacement confers durability and improved
      long-term clinical outcome without a need for long-term antithrombotic therapies.
      This approach has been successfully used in canine patients, including small
      breed dogs. Methods for mitral valve repair applicable to small dogs are
      described.

PMID- 22366572
TI  - The mechanobiology of mitral valve function, degeneration, and repair.
AB  - In degenerative valve disease, the highly organized mitral valve leaflet matrix
      stratification is progressively destroyed and replaced with proteoglycan rich,
      mechanically inadequate tissue. This is driven by the actions of originally
      quiescent valve interstitial cells that become active contractile and migratory
      myofibroblasts. While treatment for myxomatous mitral valve disease in humans
      ranges from repair to total replacement, therapies in dogs focus on treating the
      consequences of the resulting mitral regurgitation. The fundamental gap in our
      understanding is how the resident valve cells respond to altered mechanical
      signals to drive tissue remodeling. Despite the pathological similarities and
      high clinical occurrence, surprisingly little mechanistic insight has been
      gleaned from the dog. This review presents what is known about mitral valve
      mechanobiology from clinical, in vivo, and in vitro data. There are a number of
      experimental strategies already available to pursue this significant opportunity,
      but success requires the collaboration between veterinary clinicians, scientists,
      and engineers.

PMID- 22366573
TI  - Echocardiographic assessment of canine degenerative mitral valve disease.
AB  - Degenerative mitral valve disease (MVD), the most common acquired heart disease
      in small-sized dogs, is characterized by valvular degeneration resulting in
      systolic mitral valve regurgitation (MR). Worsening of MR leads to several
      combined complications including cardiac remodeling, increased left ventricular
      filling pressure, pulmonary arterial hypertension, and myocardial dysfunction.
      Conventional two-dimensional, M-mode, and Doppler examination plays a critical
      role in the initial and longitudinal assessment of dogs affected by MVD,
      providing information on mitral valve anatomy, MR severity, left ventricular (LV)
      size and function, as well as cardiac and vascular pressures. Several standard
      echocardiographic variables have been shown to be related to clinical outcome.
      Some of these markers (e.g., left atrium to aorta ratio, regurgitation fraction,
      pulmonary arterial pressure) may also help in identifying asymptomatic MVD dogs
      at higher risk of early decompensation, which remains a major issue in practice.
      However, both afterload and preload are altered during the disease course. This
      represents a limitation of conventional techniques to accurately assess
      myocardial function, as most corresponding variables are load-dependent. Recent
      ultrasound techniques including tissue Doppler imaging, strain and strain rate
      imaging, and speckle tracking echocardiography, provide new parameters to assess
      regional and global myocardial performance (e.g., myocardial velocities and
      gradients, deformation and rate of deformation, and mechanical synchrony). As
      illustration, the authors present new data obtained from a population of 91 dogs
      (74 MVD dogs, 17 age-matched controls) using strain imaging, and showing a
      significant longitudinal systolic alteration at the latest MVD heart failure
      stage.

PMID- 22366574
TI  - A comparison of friendship quality and social functioning among children with
      perinatally acquired HIV, children with persistent asthma, and healthy children
      of HIV-positive mothers.
AB  - OBJECTIVE: To examine the friendships and social expectations of children with
      perinatally acquired HIV and compare them to children with moderate to severe
      persistent asthma and healthy children of HIV-positive mothers. METHODS: 70
      children (ages 8-14 years) were recruited from pediatric allergy and immunology
      multidisciplinary clinics and hospital-based HIV-support programming. Children
      completed measures of friendship quality and interpersonal functioning.
      Caregivers completed a measure of child psychosocial functioning. RESULTS:
      Children with asthma, not HIV, demonstrated poorer indicators of friendship and
      the most negative social expectations of the three groups. Children with HIV
      maintained best friendships and rated themselves as socially well-adjusted.
      CONCLUSIONS: Comprehensive multidisciplinary services and ancillary supports may
      have buffered against stressors and facilitated positive psychosocial outcomes in
      children with HIV. Children with asthma displayed higher disease activity,
      possibly contributing to poorer outcomes. Results suggest a need to better
      understand the protective factors that enhance social functioning in children
      with HIV.

PMID- 22366575
TI  - Commentary: examination of health and behavioral code reimbursement from private
      payers in the context of clinical multidisciplinary pediatric obesity treatment.

PMID- 22366576
TI  - Generation of immigration and body mass index in Canadian youth.
AB  - OBJECTIVE: To investigate the role of acculturation, as measured by generational
      status, on body mass index (BMI) in a sample of Canadian youth. METHODS:
      Population-based data from the National Longitudinal Survey of Children and Youth
      were used. Participants were divided into 2 age ranges: children aged 6-11 years
      (n = 14,287) and adolescents aged 12-17 years (n = 12,155). Youth were classified
      into one of five generations of immigration: first-generation, second-generation,
      mixed-generation, third-generation, and Aboriginal. Parent- and self-report
      height and weight were used to calculate BMI Z-scores. RESULTS: Generation of
      immigration was significantly related to BMI Z-score in both childhood and
      adolescence. First-generation immigrants had more weight gain compared to other
      groups during adolescence, but not during childhood. CONCLUSIONS: Acculturation,
      as measured by generation of immigration, is an important predictor of BMI in
      Canadian children and adolescents.

PMID- 22366577
TI  - Analysis of a calcium-binding EF-hand protein family in Fasciola gigantica.
AB  - Transcriptome data supports the notion of a Platyhelminthes-specific protein
      family that is characterized by combination of two N-terminal EF-hands and a C
      terminal dynein light chain-like domain. Family members in schistosomes induce an
      IgE response that has been connected with resistance to reinfection in
      schistosomiasis and is considered as a marker of protection. In the present
      study, we have compared three homologs of the liver fluke Fasciola gigantica for
      their immunological properties in mouse. Antisera raised against the recombinant
      proteins detected the native proteins in tegumental type tissues and epithelial
      linings of excretory system and intestinal tract. The recombinant EF-hand domains
      induced strong IgG and IgE responses in immunised mice while only weak to
      moderate responses were observed against the complete recombinant proteins and
      their DLC-like domains. Parasite crude worm and tegumental extract antisera
      reacted predominantly with one isoform and its EF-hand domain. Sera of F.
      gigantica infected mice did not react with the recombinant proteins. The RNA
      products of the three genes were detected from the metacercarial up to the adult
      stage. These observations indicate that the investigated EF-hand proteins are not
      at the frontier of humoral host/parasite interaction in acute fascioliasis
      gigantica in mouse but are acting as intracellular proteins in tissues that
      interface with the parasite's environment or tubular tracts.

PMID- 22366578
TI  - Fischoederius cobboldi: A scanning electron microscopy investigation of surface
      morphology of adult rumen fluke.
AB  - Adults Fischoederius cobboldi are conical-shaped, concave ventrally and convex
      dorsally, measures about 8-10mm in length and 4-6mm in width across the mid
      section. Scanning electron microscopy (SEM) of entire body showed that the
      tegumental surface exhibits highly corrugation and transverse folds alternating
      with grooves and without spines. At higher magnification, the surface of each
      fold is further increased with a meshwork of ridges separated by irregular-sized
      pits. The ventral surface has more complex corrugations and invaginations than
      those of the dorsal surface of the body. Both anterior and posterior suckers have
      thick edges covered with transverse folds and appear spineless. The genital pore
      is located at the anterior one-third of the body. There are two types of sensory
      papillae on the surface: type 1 is bulbous in shape and nipple-like tips,
      measuring 10-15 MUm in diameter at the base, and also type 2 is a similar shape
      and has short cilia on tips. These sensory papillae occur in large clusters, each
      having between 7 and 25 units depending on the region of the body. Clusters of
      papillae on the ventral surface and around the anterior suckers tend to be more
      abundant and larger in size. The dorsal side of the body exhibit similar surface
      features, but papillae appear less numerous and are smaller. Corrugations and
      invaginations of the dorsal aspect are also less extensive than those on the
      ventral surface of the body.

PMID- 22366579
TI  - Tumor necrosis factor-associated susceptibility to type 1 diabetes is caused by
      linkage disequilibrium with HLA-DR3 haplotypes.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine
      involved in the pathogenesis of autoimmune type 1 diabetes (T1D). The TNF gene
      locus is located in the major histocompatibility complex (MHC) class III region
      and its genetic polymorphisms have been reported to be associated with T1D.
      However, it is not clear whether these associations are primary or caused by
      their linkage disequilibrium with other predisposing genes within the MHC. We
      have tested 2 TNF-alpha single nucleotide polymorphisms at positions -308G/A and 
      238G/A in the 5' untranslated region and a (GT)n microsatellite TNFa in the North
      Indian healthy population and T1D patients with known HLA-A-B-DR-DQ haplotypes.
      The allele frequencies of TNFa5, -308A, and -238G were determined to be
      significantly increased among patients compared with controls. Although the
      observed positive association of -238G was caused by its presence on all 3 DR3(+)
      groups, namely, B8-DR3-DQ2, B50-DR3-DQ2, and B58-DR3-DQ2 haplotypes associated
      with T1D in this population, the increase of the -308A allele was caused by its
      association with the latter 2 haplotypes. On the other hand, TNF -308G occurred
      on B8-DR3 haplotypes along with -238G and TNFa5 alleles, particularly in T1D
      patients with late disease onset (at >20 years of age). These results indicate
      that TNF associations with T1D are caused by their linkage disequilibrium with
      specific HLA-DR3-DQ2 haplotypes in the Indian population. Because polymorphisms
      in the promoter region regulate TNF expression levels (e.g., -308A), they retain
      crucial immunological significance in the development of T1D and its management.

PMID- 22366580
TI  - In vitro induction of specific CD8+ T lymphocytes by tumor-associated antigenic
      peptides in patients with oral squamous cell carcinoma.
AB  - The aim of this study was to clarify candidate peptides for peptide-based
      specific immunotherapy of patients with oral squamous cell carcinoma (SCC).
      Thirteen peptides were examined for in vitro induction of peptide-specific CD8(+)
      T lymphocyte (CD8(+)TL) activity in peripheral blood mononuclear cells from 35
      patients with oral SCC. A correlation between the induction ability of CD8(+)TL
      and in vivo immune response of host was carried out immunohistochemically in 23
      patients. Peptide-specific activities of CD8(+)TL for at least one peptide were
      detectable in 21/35 patients (60.0%). The potent peptides were SART-1(690) in
      9/35 (25.7%), SART-2(93), and ART4(75) in 7/35 (20.0%), respectively. In the 9
      patients with SART-1(690)-specific activity, the whole of activities was
      significantly inducible for more number of other peptides compared to that in 26
      patients without the activity (P=0.035). Cellular responses in 7 patients with
      SART-1(690)-specific activity were significantly stronger than those in 16
      patients without the activity (P=0.027). Furthermore, the number of CD3(+) T
      cells around the SCC was also significantly different between the 2 groups of
      patients (P=0.041). In conclusion, SART-1(690), SART-2(93), and ART4(75) could be
      applicable as peptide-based specific immunotherapies for the majority of patients
      with oral SCC.

PMID- 22366581
TI  - Interleukin-12 inhibits the survival of human colon cancer stem cells in vitro
      and their tumor initiating capacity in mice.
AB  - Interleukin-12 (IL-12) is a potent immunomodulatory cytokine with unknown direct
      effect on the property of cancer stem cells (CSCs). In this study, we
      investigated the capacity of IL-12 to regulate the self-renewal and
      differentiation of human colon CSCs in vitro, as well as the effect of IL-12 on
      the growth of tumors initiated by CSCs in mice. After over-expression of IL-12
      with lentiviral transfection, CSCs exhibited reduced invasiveness and tumorsphere
      formation in association with increased apoptosis in vitro. After injection into
      NOD/SCID mice, tumors initiated by CSCs transfected with IL-12 showed markedly
      reduced rate of growth. Mechanistic studies revealed that over-expression of IL
      12 reduced the expression of IL-4 and STAT6 in CSCs. Thus, our study demonstrates
      a potentially beneficial role of IL-12 in directly limiting the malignant
      phenotype of CSCs.

PMID- 22366582
TI  - Selectin-deficiency reduces the number of spontaneous metastases in a xenograft
      model of human breast cancer.
AB  - Metastasis formation is a complex process still poorly understood. Previous work
      in a colon cancer xenograft model showed that E(ndothelial) and P(latelet)
      selectins mediate spontaneous metastasis to the lungs. To investigate the
      functional role of selectins in breast cancer, human DU4475 breast cancer cells
      were injected subcutaneously into pfp-/-rag2-/- mice and in all their selectin
      deficient variants (EP-/-, E-/- and P-/-). Pfp-/-rag2-/- mice as well as all
      their selectin-deficient variants developed primary tumours and spontaneous
      metastases. Compared with the wild-type mice, disseminated tumours cells were
      significantly lower (74% reduction, P=0.046) in the bone marrow of selectin
      deficient mice. Pfp-/-rag2-/- mice developed significantly higher numbers of lung
      metastases (6644.83+/-741.77) than the E-/- (4053.33+/-112.58; P=0.002) and the
      EP-/- pfp-/-rag2-/- mice (4665.65+/-754.50; P<0.001). The results indicate that E
      and P-selectins play a role in spontaneous metastasis formation both into bone
      marrow and lungs. However, spontaneous metastasis was not completely abrogated,
      hence additional cell adhesion molecules must be involved in the metastatic
      spread.

PMID- 22366583
TI  - Mild traumatic brain injury (concussion), posttraumatic stress disorder, and
      depression in U.S. soldiers involved in combat deployments: association with
      postdeployment symptoms.
AB  - OBJECTIVES: Several studies have examined the relationship between
      concussion/mild traumatic brain injury (mTBI), posttraumatic stress disorder
      (PTSD), depression, and postdeployment symptoms. These studies indicate that the
      multiple factors involved in postdeployment symptoms are not accounted for in the
      screening processes of the Department of Defense/Veteran's Affairs months after
      concussion injuries. This study examined the associations of single and multiple
      deployment-related mTBIs on postdeployment health. METHODS: A total of 1502 U.S.
      Army soldiers were administered anonymous surveys 4 to 6 months after returning
      from deployment to Iraq or Afghanistan assessing history of deployment-related
      concussions, current PTSD, depression, and presence of postdeployment physical
      and neurocognitive symptoms. RESULTS: Of these soldiers, 17% reported an mTBI
      during their previous deployment. Of these, 59% reported having more than one.
      After adjustment for PTSD, depression, and other factors, loss of consciousness
      was significantly associated with three postconcussive symptoms, including
      headaches (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.1-2.3).
      However, these symptoms were more strongly associated with PTSD and depression
      than with a history of mTBI. Multiple mTBIs with loss of consciousness increased
      the risk of headache (OR = 4.0, 95% CI = 2.4-6.8) compared with a single
      occurrence, although depression (OR = 4.2, 95% CI = 2.6-6.8) remained as strong a
      predictor. CONCLUSIONS: These data indicate that current screening tools for mTBI
      being used by the Department of Defense/Veteran's Affairs do not optimally
      distinguish persistent postdeployment symptoms attributed to mTBI from other
      causes such as PTSD and depression. Accumulating evidence strongly supports the
      need for multidisciplinary collaborative care models of treatment in primary care
      to collectively address the full spectrum of postwar physical and neurocognitive
      health concerns.

PMID- 22366584
TI  - Acculturation, maternal cortisol, and birth outcomes in women of Mexican descent.
AB  - OBJECTIVE: This study investigated the effects of acculturation on cortisol, a
      biological correlate of maternal psychological distress, and perinatal infant
      outcomes, specifically gestational age at birth and birth weight. METHODS: Fifty
      five pregnant women of Mexican descent were recruited from a community hospital,
      and their saliva samples were collected at home for 3 days during pregnancy at 15
      to 18 weeks (early), 26 to 32 weeks (mid), and more than 32 weeks (late) of
      gestation and once in the postpartum period (4-12 weeks). These values were used
      to determine the diurnal cortisol slope at each phase of pregnancy. Mothers also
      completed an acculturation survey and gave permission for a medical chart review
      to obtain neonate information. RESULTS: Multiple regression analyses determined
      that greater acculturation levels significantly predicted earlier infant
      gestational age at birth (R(2) = 0.09, p = .03). Results from t tests revealed
      that mothers of low-birth-weight infants (<2500 g) had significantly higher
      acculturation scores than mothers of infants with birth weight greater than 2500
      g (t = -2.95, p = .005). A blunted maternal cortisol slope during pregnancy was
      also correlated with low birth weight (r = -0.29, p = .05) but not gestational
      age (r = -0.08, p = .59). In addition, more acculturated women had a flatter
      diurnal cortisol slope late in pregnancy (R(2) = 0.21, p = .01). Finally, diurnal
      maternal cortisol rhythms were identified as a potential mediator between
      increased acculturation and birth weight. CONCLUSIONS: This study associated
      increased acculturation with perinatal outcomes in the US Mexican population.
      This relationship may be mediated by prenatal maternal diurnal cortisol, which
      can program the health of the fetus leading to several adverse perinatal
      outcomes.

PMID- 22366585
TI  - Association of in vivo beta-adrenergic receptor sensitivity with inflammatory
      markers in healthy subjects.
AB  - OBJECTIVE: Several stress-related states and conditions that are considered to
      involve sympathetic overactivation are accompanied by increased circulating
      levels of inflammatory immune markers. Prolonged sympathetic overactivity
      involves increased stimulation of the beta-adrenergic receptor (beta-AR).
      Although prior research suggests that one mechanism by which sympathetic
      stimulation may facilitate inflammation is via beta-AR activation, little work
      has focused on the relationship between circulating inflammatory immune markers
      and beta-AR function within the human body (in vivo). We examined whether
      decreased beta-AR sensitivity, an indicator of prolonged beta-adrenergic
      overactivation and a physiological component of chronic stress, is related to
      elevated levels of inflammatory immune markers. METHODS: Ninety-three healthy
      participants aged 19 to 51 years underwent the chronotropic 25 dose isoproterenol
      test to determine in vivo beta-AR function. Circulating levels of C-reactive
      protein, interleukin 6, and soluble tumor necrosis factor receptor 1 were
      determined. RESULTS: beta-AR sensitivity was lower in people with higher C
      reactive protein concentrations (r = 0.326, p = .003). That relationship remained
      significant after controlling for sociodemographic and health variables such as
      age, sex, ethnicity, body mass index, mean arterial blood pressure, heart rate,
      leisure-time exercise, and smoking status. No significant relationship was found
      between chronotropic 25 dose and interleukin 6 or soluble tumor necrosis factor
      receptor 1. CONCLUSIONS: This study demonstrates a link between in vivo beta
      adrenergic receptor function and selected circulating inflammatory markers (CRP)
      in humans. Future studies in specific disease states may be promising.

PMID- 22366587
TI  - Stress-induced alterations in coagulation: assessment of a new hemoconcentration
      correction technique.
AB  - OBJECTIVE: For the examination of psychological stress effects on coagulation,
      the Dill and Costill correction (DCC) for hemoconcentration effects has been used
      to adjust for stress-induced plasma volume changes. Although the correction is
      appropriate for adjusting concentrations of various large blood constituents, it
      may be inappropriate for time-dependent or functional coagulation assays. Two new
      plasma reconstitution techniques for correcting hemoconcentration effects on
      stress-induced changes in coagulation were compared with the DCC. METHODS: Blood
      was collected from 31 men during baseline, the Trier Social Stress Test (TSST),
      and after 20-minute recovery. For the reconstitution techniques, TSST plasma
      samples were reconstituted with either baseline plasma or physiological saline
      equal to the amount of plasma lost during stress. RESULTS: Uncorrected activated
      partial thromboplastin time (APTT) decreased, whereas fibrinogen, factor VIII
      clotting activity (FVIII:C), D-dimer and prothrombin time (PT%) increased
      significantly during the TSST. The DCC produced a significantly greater decrease
      in APTT during stress compared to uncorrected APTT, a significant decrease in PT%
      compared to uncorrected PT%, and stress D-dimer and fibrinogen and FVIII:C being
      no different than baseline. APTT, fibrinogen, D-dimer and PT% after saline
      reconstitution were not different from baseline, whereas FVIII:C after saline
      reconstitution remained elevated. APTT, PT%, fibrinogen and D-dimer after plasma
      reconstitution were no different from uncorrected values, whereas FVIII:C
      remained significantly elevated. CONCLUSIONS: The observed changes in coagulation
      are likely in part a consequence of stress and hemoconcentration, but the DCC
      seems to be an inappropriate hemoconcentration correction technique of time
      dependent assays. The saline reconstitution technique may be more biologically
      relevant when examining stress-hemoconcentration effects on coagulation.

PMID- 22366586
TI  - Association of physical versus affective depressive symptoms with cardiac event
      free survival in patients with heart failure.
AB  - OBJECTIVE: To determine whether physical depressive symptoms inflate the
      association between depressive symptoms as measured with the nine-item Patient
      Health Questionnaire (PHQ-9) and cardiac event-free survival in patients with
      heart failure (HF). METHODS: A total of 210 patients with HF were recruited from
      HF clinics affiliated with two academic medical centers. The PHQ-9 was used to
      assess levels of depressive symptoms. Cardiac event-free survival data (cardiac
      death, cardiac hospitalization, or cardiac emergency department visit) were
      collected for a median follow-up of 360 days. Cox proportional hazards regression
      analyses were performed separately for physical and affective depressive symptom
      dimensions of the PHQ-9 to examine predictive ability for time to the first
      cardiac event. RESULTS: Scores of both physical and affective depressive symptom
      dimensions of the PHQ-9 predicted time to the first cardiac event in separate
      unadjusted models. However, scores of the physical depressive symptom dimension
      did not predict time to the first cardiac events, whereas scores of the affective
      depressive symptom dimension remained as an independent predictor (hazard ratio =
      1.12, 95% confidence interval = 1.03-1.22) after controlling for health status
      (comorbidities and the New York Heart Association functional class) and clinical
      and sociodemographic factors. CONCLUSIONS: Affective depressive symptoms, not
      physical depressive symptoms, predicted time to the first cardiac event
      independent of health status and clinical and sociodemographic characteristics.
      The use of the full PHQ-9 does not inflate the relationship of depressive
      symptoms to cardiac event-free survival. Thus, clinicians can use the PHQ-9 to
      assess depressive symptoms in their patients with HF without concern that the
      instrument overestimates the relationship between depressive symptoms and
      outcomes.

PMID- 22366588
TI  - A brief history of neurosurgery in Chile and its incidence in Latin America.

PMID- 22366589
TI  - Smoking cessation counseling in women with genital intraepithelial neoplasia.
AB  - OBJECTIVE: Cigarette smoking is a risk factor for cervical, vaginal, vulvar, and
      anal dysplasia. We will study the prevalence of cigarette smoking in patients
      with genital dysplasia and effect of counseling on smoking cessation. METHODS:
      All patients with genital dysplasia were screened for smoking history. One
      clinician provided smoking cessation counseling using the US Department of Health
      5 A's technique: ask patients about their smoking status, advise smokers to quit,
      assess their readiness to quit, assist with their smoking cessation effort, and
      arrange for follow-up visits. Patients were informed on how smoking may cause
      worsening of genital dysplasia and increased risk of progression to cancer. Each
      patient received 2 counseling sessions, but no pharmacological or psychological
      interventions. Smoking cessation was evaluated by patient self-report via phone
      or during clinic visits. RESULTS: From January 2007 to December 2010, 344
      patients were referred to our gynecologic oncology clinic for evaluation of
      genital dysplasia. Patients who were smokers (n=125, 36%) were counseled to cease
      smoking in 2 counseling sessions, with 100% compliance for attendance. At study
      analysis (July 2011), 83 patients still smoke and 40 patients quit smoking
      (smoking cessation rate of 32%). Caucasian patients (P=.0013) and patients with
      vulvar dyplasia (P=.411) seemed to smoke more than other races and patients with
      cervical/vaginal dysplasia respectively. CONCLUSION: Smoking cessation counseling
      for the genital dysplasia patients who smoked was associated with smoking
      cessation in 32% of the patients.

PMID- 22366591
TI  - Bevacizumab rechallenge after first line maintenance bevacizumab.

PMID- 22366592
TI  - Surgical cytoreduction in patients with metastatic uterine leiomyosarcoma at the
      time of initial diagnosis.
AB  - OBJECTIVE: To determine whether cytoreduction is associated with improved outcome
      in patients newly diagnosed with metastatic uterine leiomyosarcoma (LMS).
      METHODS: We retrospectively identified all patients treated at our institution
      for high-grade uterine LMS with extrauterine disease at the time of initial
      diagnosis from 7/1/82 to 7/31/07. Pattern of disease spread was classified as
      intraperitoneal (IP) or extraperitoneal (EP). Progression-free survival (PFS) and
      overall survival (OS) were determined from date of initial surgery using Kaplan
      Meier estimates. RESULTS: We identified 96 cases. Median age was 54 years (range,
      23-81). IP disease was seen in 48 (50%) and EP in 48 (50%). A complete gross
      resection of all tumor was achieved in 41/84 (49%). Recurrence or progression was
      noted in 93 (97%); 81 (84%) have died. Median PFS and OS for the entire cohort
      was 9.7 months (range, 6.7-10.9) and 20.2 months (range, 15.5-24.8),
      respectively. All 8 non-surgical cases died within 30 months of diagnosis. Median
      PFS was 14.2 months (range, 11.4-16.9) for those with a complete gross resection
      versus 6.8 months (range, 4.1-9.5) for those with any residual disease (P=0.002).
      Median OS was 31.9 months (range, 3.3-60.4) versus 20.2 months (range, 11.8
      28.6), respectively (P=0.04). On multivariate analysis, no residual disease was
      independently associated with PFS when adjusting for disease distribution (IP vs
      EP) and the use of chemotherapy but not OS. CONCLUSIONS: Surgical cytoreduction
      of metastatic uterine LMS was independently associated with PFS but not OS in
      cases selected for surgery. The improvement in PFS must be weighed against the
      morbidity of surgery.

PMID- 22366593
TI  - Prognostic determinants in patients with uterine and ovarian clear carcinoma.
AB  - OBJECTIVE: The purpose of this study is to analyze and compare the demographics,
      treatment, recurrence, and survival rates in patients with uterine clear cell
      carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). METHODS: A
      retrospective review of the Cancer Registry database was performed. All patients
      with UCCC and OCCC who underwent surgical staging at the two participating
      institutions, between January, 1995 and December, 2007, were identified.
      Categorical variables were evaluated by Chi square test. Survival estimates were
      plotted utilizing the Kaplan-Meier method. RESULTS: Analysis of 41 women with
      UCCC and 121 with OCCC was performed. In patients with OCCC, 48.4% had localized
      disease, 18.9% had regional spread, 31.1% had distant metastasis, and in 1.6%
      spread is unknown; compared to UCCC, 41.5% had localized disease, 12.2% regional
      spread, and 46.3% distant metastasis (p=0.2). The median progression free
      survival was 31.4 months in women with UCCC, compared to 145 months in patients
      with OCCC (p=0.04). UCCC women had a median overall survival of 39.5 months,
      compared to 155.8 months in patients with OCCC (p=0.002). In the multivariate Cox
      regression model, age>55 years old, tumor extension, optimal cytoreduction, and
      platinum-based chemotherapy were identified as independent predictors of overall
      survival. UCCC vs. OCCC was not associated with decreased overall survival in
      multivariate analysis. CONCLUSION: OCCC and UCCC have the same rate of localized
      disease, regional spread and distant metastasis. After controlling for age, tumor
      extension, optimal cytoreduction, and platinum based chemotherapy, UCCC was not
      associated with decreased overall survival compared to OCCC.

PMID- 22366594
TI  - A phase II evaluation of belinostat and carboplatin in the treatment of recurrent
      or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal
      carcinoma: a Gynecologic Oncology Group study.
AB  - BACKGROUND: Patients with recurrent ovarian cancer have limited options,
      especially in the context of relapse less than six months from primary platinum
      based therapy. This Gynecologic Oncology Group (GOG) study was conducted to
      evaluate the impact of the histone deacetylase inhibitor, belinostat, in
      combination with carboplatin in women with platinum-resistant ovarian cancer.
      METHODS: Eligible patients had measurable, recurrent disease within six months of
      their last dose of a platinum-based combination. Belinostat was dosed at 1000
      mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles.
      The primary endpoint was overall response rate (ORR), using a two-stage design.
      RESULTS: Twenty-nine women enrolled on study and 27 were evaluable. The median
      number of cycles given was two (range 1-10). One patient had a complete response
      and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve
      patients had stable disease while eight had increasing disease. Response could
      not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10%
      of treated patients were uncommon and limited to neutropenia (22.2%),
      thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free
      survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at
      least six months was noted in 29.6% of patients. Due to the lack of drug
      activity, the study was closed after the first-stage. CONCLUSIONS: The addition
      of belinostat to carboplatin had little activity in a population with platinum
      resistant ovarian cancer.

PMID- 22366595
TI  - Overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) is
      associated with human cervical cancer malignancy, progression and prognosis.
AB  - OBJECTIVE: To investigate the correlation of cystic fibrosis transmembrane
      conductance regulator (CFTR) to cervical cancer progression and prognosis by
      examining CFTR expression levels in different cervical tissues and cell lines.
      METHODS: Paraffin-embedded cervical tissue samples (n=192) were collected for
      immunohistochemistry (IHC), while fresh cervical tissue samples (n=165) and human
      cervical cell lines were collected for protein and mRNA detection by quantitative
      real-time PCR and western blot, respectively. Correlations between CFTR
      expression levels to cancer clinicopathologic features and prognosis were
      statistically analyzed. RESULTS: Both CFTR mRNA and protein expression gradually
      increased from normal to precancerous (LSIL, HSIL) and cervical cancer tissues
      (p<0.05). Furthermore, CFTR expression level was well-correlated to tumor stage
      (p<0.001), histological grades (p<0.001), lymphatic metastasis (p<0.001),
      vascular invasion (p<0.05), interstitial invasive depth (p<0.05), tumor size
      (p<0.05) and HPV infection (p<0.05). In vitro, CFTR mRNA and protein were
      expressed strongly both in SiHa and HeLa, but little was seen in Caski and H8
      (p<0.05). More importantly, overexpression of CFTR conferred significantly poorer
      survival in cervical carcinoma (Log rank p=0.028), although it was not an
      independent predictor for prognosis according to multivariate analysis (p>0.05).
      CONCLUSIONS: These results suggest that higher CFTR expression is closely
      associated with cervical cancer progression, aggressive behaviors and poorer
      prognosis, indicating that CFTR may function as a novel tumor marker, a
      prospective prognostic indicator and a potential therapeutic target for cervical
      cancer.

PMID- 22366596
TI  - The effect of hysterectomy on survival of patients with borderline ovarian
      tumors.
AB  - OBJECTIVE: The classically recommended surgical treatment of borderline ovarian
      tumors (BOTs) includes hysterectomy in addition to bilateral adnexectomy.
      Possible reasons for hysterectomy might be a high frequency of uterine
      involvement and its favorable effect on survival. The purpose of the present
      study was to assess the frequency of uterine involvement in patients with BOTs
      and the effect of hysterectomy on survival. METHODS: All incident cases of
      histological confirmed BOTs diagnosed in Israeli Jewish women between March 1
      1994 and June 30 1999, were identified. Clinical and pathological characteristics
      were abstracted from medical records. Patients with tumors grossly confined to
      the ovaries (apparently stage I) were considered to have had surgical staging
      when at least hysterectomy, bilateral salpingooophorectomy, omentectomy and
      pelvic lymph node sampling were done. RESULTS: The study group comprised 225
      patients. Hysterectomy was performed in 147 (65.31%) patients and uterine
      involvement was present in only 3 (2.0%) of them. The 13 year survival of the
      total group of patients was 85.8% and of those in apparent stage I, 88.5%. Among
      patients with tumors apparently confined to the ovaries, no significant survival
      difference was observed between unstaged and surgically staged patients. There
      was also no survival difference between the overall staged and unstaged patients
      and between patients in stages II-III who did and did not undergo hysterectomy.
      CONCLUSIONS: Our data indicate that the rate of uterine involvement in BOT is low
      and that hysterectomy does not favorably affect survival. The necessity of
      hysterectomy in BOT patients is questioned.

PMID- 22366597
TI  - Delivery success rate of engineered nanoparticles in the presence of the protein
      corona: a systems-level screening.
AB  - Nanoparticles (NPs) for medical applications are often introduced into the body
      via intravenous injections, leading to the formation of a protein corona on their
      surface due to the interaction with blood plasma proteins. Depending on its
      composition and time evolution, the corona will modify the biological behavior of
      the particle. For successful delivery and targeting, it is therefore important to
      assess on a quantitative basis how and to what extent the presence of the corona
      perturbs the specific interaction of a designed NP with its cellular target. We
      present a theoretical systems-level analysis, in which peptides have been
      covalently coupled to the surface of nanoparticles, describing the delivery
      success rate in varying conditions, with regard to protein composition of the
      surrounding fluid. Dynamic modeling and parameter sensitivity analysis proved to
      be useful and computationally affordable tools to aid in the design of NPs with
      increased success rate probability in a biological context. FROM THE CLINICAL
      EDITOR: The formation of a protein corona consisting of blood plasma proteins on
      the surface of intravenously delivered nanoparticles may modify the biological
      behavior of the particles. This team of investigators present a theoretical
      systems-level analysis of this important and often neglected phenomenon.

PMID- 22366598
TI  - Ultradeformable archaeosomes as new topical adjuvants.
AB  - Ultradeformable archaeosomes (UDA) are vesicles made of soybean
      phosphatidylcholine (SPC), sodium cholate (NaChol) and polar lipids from
      Halorubrum tebenquichense (3:1:3 wt/wt). Although ultradeformable liposomes (UDL,
      made of SPC and NaChol at 6:1 wt/wt) and UDA were neither captured nor caused
      cytotoxicity on keratinocytes, UDA was avidly captured by macrophages, their
      viability being reduced by 0.4-1.6 mg/mL phospholipids by 25 to 60%. Instead, UDL
      were poorly captured and caused no toxicity. Balb/C mice immunized by the topical
      route with four doses of ovalbumin (OVA)-loaded UDA, at 75 MUg OVA/600 MUg
      phospholipids (125 nm mean size and -42 mV zeta potential), induced IgG titers
      tenfold to 100-fold higher than those immunized with OVA-loaded UDL at the same
      dosage. Both matrices penetrate to the same skin depth (nearly 10 MUm after 1
      hour on excised human skin), being the higher topical adjuvancy and higher
      phagocytic uptake of UDA related to its glycolipid content. FROM THE CLINICAL
      EDITOR: This work summarizes key findings related to the development of
      ultradeformable archaeosomes as vehicles utilized in transdermal delivery systems
      with improved skin penetration.

PMID- 22366599
TI  - Preparation and characterization of recombinant human growth hormone-Zn2+-dextran
      nanoparticles using aqueous phase-aqueous phase emulsion.
AB  - An effective and simple method was developed to prepare spherical and uniform
      sized recombinant human growth hormone (rhGH)-Zn(2+)-dextran nanoparticles (NPs)
      for a variety of delivery applications of the delicate protein. The results
      showed that the prepared rhGH-Zn(2+)-dextran particles were spherical, glassy,
      and uniform in size. rhGH recovered from the NPs maintained its structural
      integrity and its bioactivity well, as suggested by the Nb(2)-11 cell
      proliferation assay. Using polyethylene glycol and polysaccharide to mediate
      Zn(2+)-induced precipitation has proved to be a promising method to prepare
      spherical protein-loaded NPs with desired sizes and preserved protein stability.
      FROM THE CLINICAL EDITOR: This basic science paper discusses a simple yet
      effective method to prepare spherical and uniform-sized recombinant human growth
      hormone (rhGH)-Zn(2+)-dextran nanoparticles for a variety of delivery
      applications.

PMID- 22366600
TI  - Lipid production for second generation biodiesel by the oleaginous yeast
      Rhodotorula graminis.
AB  - The increasing cost of vegetable oils is turning the use of microbial lipids into
      a competitive alternative for the production of biodiesel fuel. The oleaginous
      yeast Rhodotorula graminis is able to use a broad range of carbon sources for
      lipid production, and is able to resist some of the inhibitors commonly released
      during hydrolysis of lignocellulosic materials. Using undetoxified corn stover
      hydrolysate as substrate, the yeast achieved a lipid productivity and lipid
      content of 0.21 g/L/h and 34%w/w, respectively. The corresponding results with
      crude glycerol as carbon source were 0.15 g/L/h and 54%w/w, respectively.
      Therefore, R. graminis appears to be a suitable candidate for fermentation
      processes involving renewable resources.

PMID- 22366601
TI  - Enhanced labeling of microalgae cellular lipids by application of an electric
      field generated by alternating current.
AB  - An alternating current was used to generate an electric field to enhance the
      fluorescent labeling of microalgae cellular lipids with Nile red and LipidTOX.
      The decay of the fluorescence intensity of Chlorella vulgaris cells in 0 V/cm was
      more than 50% after 10 min, and the intensity variation was as high as 7% in 20s.
      At 2000 V/cm, the decay rate decreased to 1.22% per minute and the intensity
      fluctuation was less than 1% for LipidTOX-labeled cells. For Spirulina sp. cells
      at 0 V/cm, the fluorescence intensity increased by 10% after 10 min, whereas at
      2000 V/cm, labeling was more rapid and fluorescence intensity doubled. These
      results show that applying an electric field can improve the quality of
      fluorescence detection by alleviating decay and fluctuation or by enhancing
      signal intensity.

PMID- 22366602
TI  - Effect of S0/X0 ratio and acclimation on respirometry of activated sludge in the
      cometabolic biodegradation of phenolic compounds.
AB  - Aerobic batch biodegradation experiments and respirometric analysis were
      performed in order to investigate the effect of S(0)/X(0) (substrate/biomass)
      ratio and preliminary acclimation on bi-solute biodegradation of phenolic
      compounds. It was shown that 2-chlorophenol (2-CP) and 2-nitrophenol (2-NP) could
      be cometabolically biodegraded only with acclimated biomass in the presence of
      phenol as growth substrate. Acclimation resulted in domination of phenol
      oxidizing bacteria which could induce the necessary enzymes for cometabolic
      transformation of 2-CP and 2-NP. Biodegradation of the cometabolic compounds
      occurred even after depletion of phenol at resting cell conditions. Both
      compounds could be successfully biodegraded by the acclimated biomass at initial
      substrate concentrations as high as 300 mg/L. Respirometric analysis showed that
      the optimum S(0)/X(0) ratio ranged between 1.5 and 5.5mg COD(eq)/mg MLSS for
      cometabolic substrates 2-CP and 2-NP, whereas it was as high as 8.5mg COD(eq)/mg
      MLSS for phenol which corresponds to a phenol concentration of about 1500 mg/L.

PMID- 22366603
TI  - Quantitatively understanding reduced xylose fermentation performance in AFEXTM
      treated corn stover hydrolysate using Saccharomyces cerevisiae 424A (LNH-ST) and
      Escherichia coli KO11.
AB  - Reduced xylose fermentation performance has been an issue during fermentation of
      AFEXTM hydrolysate using Saccharomyces cerevisiae 424A (LNH-ST) or Escherichia
      coli KO11. To better understand why fermentation performance is reduced, we
      quantitatively studied the effects of compounds present in the fermentation broth
      on xylose consumption. The compounds include biomass degradation products,
      ethanol and fermentation metabolites. The xylose consumption capability of E.
      coli KO11 was almost totally inhibited by the presence of both degradation
      products and ethanol. On the other hand, for S. cerevisiae 424A, 89% reduction of
      xylose consumption rate was found during hydrolysate fermentation. Degradation
      products, ethanol and fermentation metabolites were responsible for 32%, 24% and
      33% of such reduction, respectively. Those results suggest that to further
      improve the xylose fermentation in hydrolysate, strains should be selected not
      only for degradation products tolerance but also for ethanol and fermentation
      metabolites tolerance.

PMID- 22366604
TI  - An economic, sustainability, and energetic model of biodiesel production from
      microalgae.
AB  - A new process evaluation methodology of microalgae biodiesel has been developed.
      Based on four evaluation criteria, i.e. the net energy ratio (NER), biodiesel
      production costs, greenhouse gases (GHG) emission rate and water footprint, the
      model compares various technologies for each step of the process, from
      cultivation to oil upgrading. An innovative pathway (hybrid raceway/PBR
      cultivation system, belt filter press for dewatering, wet lipid extraction, oil
      hydrotreating and anaerobic digestion of residues) shows good results in
      comparison to a reference pathway (doubled NER, lower GHG emission rate and water
      footprint). The production costs are still unfavourable (between 1.94 and 3.35
      ?/L of biodiesel). The most influential parameters have been targeted through a
      global sensitivity analysis and classified: (i) lipid productivity, (ii) the
      cultivation step, and (iii) the downstream processes. The use of low-carbon
      energy sources is required to achieve significant reductions of the biodiesel GHG
      emission rate compared to petroleum diesel.

PMID- 22366605
TI  - Comparative assessment of single-stage and two-stage anaerobic digestion for the
      treatment of thin stillage.
AB  - A comparative evaluation of single-stage and two-stage anaerobic digestion
      processes for biomethane and biohydrogen production using thin stillage was
      performed to assess the impact of separating the acidogenic and methanogenic
      stages on anaerobic digestion. Thin stillage, the main by-product from ethanol
      production, was characterized by high total chemical oxygen demand (TCOD) of 122
      g/L and total volatile fatty acids (TVFAs) of 12 g/L. A maximum methane yield of
      0.33 L CH(4)/gCOD(added) (STP) was achieved in the two-stage process while a
      single-stage process achieved a maximum yield of only 0.26 L CH(4)/gCOD(added)
      (STP). The separation of acidification stage increased the TVFAs to TCOD ratio
      from 10% in the raw thin stillage to 54% due to the conversion of carbohydrates
      into hydrogen and VFAs. Comparison of the two processes based on energy outcome
      revealed that an increase of 18.5% in the total energy yield was achieved using
      two-stage anaerobic digestion.

PMID- 22366606
TI  - Biodegradation of rhamnolipids in liquid cultures: effect of biosurfactant
      dissipation on diesel fuel/B20 blend biodegradation efficiency and bacterial
      community composition.
AB  - Bacterial utilization of rhamnolipids during biosurfactant-supplemented
      biodegradation of diesel and B20 (20% biodiesel and 80% diesel v/v) fuels was
      evaluated under conditions with full aeration or with nitrate and nitrite as
      electron acceptors. Rhamnolipid-induced changes in community dynamics were
      assessed by employing real-time PCR and the ddCt method for relative
      quantification. The experiments with rhamnolipids at 150 mg/l, approx. double
      critical micelle concentration (CMC) and diesel oil confirmed that rhamnolipids
      were readily degraded by a soil-isolated consortium of hydrocarbon degraders in
      all samples, under both aerobic and nitrate-reducing conditions. The presence of
      rhamnolipids increased the dissipation rates for B20 constituents under aerobic
      conditions, but did not influence the biodegradation rate of pure diesel. No
      effect was observed under nitrate-reducing conditions. The biodegradation of
      rhamnolipids did not favor the growth of any specific consortium member, which
      proved that the employed biosurfactant did not interfere with the microbial
      equilibrium during diesel/biodiesel biodegradation.

PMID- 22366607
TI  - Combined biomimetic and inorganic acids hydrolysis of hemicellulose in Miscanthus
      for bioethanol production.
AB  - Combined acid catalysis was employed as a pretreatment alternative with combined
      acid catalysts blending sulfuric acid with two biomimetic acids, trifluoroacetic
      acid (TFA) and maleic acid (MA), respectively. The influences of acid blending
      ratio, temperature, and acid dosage on pretreatment performance were
      investigated. A synergistic effect on hemicellulose decomposition was observed in
      the combined acid hydrolysis, which greatly increased xylose yield, although
      TFA/MA would induce more total phenols. Besides, combined TFA pretreatment could
      efficiently prevent xylose degradation. Fermentation tests of the acid-catalyzed
      hydrolysates with overliming showed that compared to H(2)SO(4) pretreatment, TFA
      and MA pretreatments improved overall ethanol yield with an increase by 27-54%.
      Combined acid catalysis was shown as a feasible pretreatment method for its
      improved sugar yield, reduced phenols production and catalyst costs.

PMID- 22366608
TI  - Treatment of ammonium-rich swine waste in modified porphyritic andesite fixed-bed
      anaerobic bioreactor.
AB  - In this study, a modified porphyritic andesite (WRS) was developed as ammonium
      adsorbent and bed material for the anaerobic digestion of ammonium-rich swine
      waste. The performance in bioreactors with modified WRS, natural WRS, calcium
      chloride and no additives was investigated. The bioreactor with modified WRS
      exhibited the best performance, with start-up time on the 7th day, methane yield
      of 359.71 ml/g-VS, and COD removal of 67.99% during all 44 days of the experiment
      at 35 degrees C. The effective ammonium adsorption and essential ions
      dissociation for microorganisms by modified WRS, as well as the immobilization of
      microbial on the surface of the modified WRS play a great role on the high
      efficiency anaerobic digestion of ammonium-rich swine waste.

PMID- 22366609
TI  - Bio-electrochemical remediation of real field petroleum sludge as an electron
      donor with simultaneous power generation facilitates biotransformation of PAH:
      effect of substrate concentration.
AB  - Remediation of real-field petroleum sludge was studied under self-induced
      electrogenic microenvironment with the function of variable organic loads (OLs)
      in bio-electrochemical treatment (BET) systems. Operation under various OLs
      documented marked influence on both electrogenic activity and remediation
      efficiency. Both total petroleum hydrocarbons (TPH) and its aromatic fraction
      documented higher removal with OL4 operation followed by OL3, OL2, OL1 and
      control. Self-induced biopotential and associated multiple bio-electrocatalytic
      reactions during BET operation facilitated biotransformation of higher ring
      aromatics (5-6) to lower ring aromatic (2-3) compounds. Asphaltenes and NSO
      fractions showed negligible removal during BET operation. Higher electrogenic
      activity was recorded at OL1 (343mV; 53.11mW/m(2), 100Omega) compared to other
      three OLs operation. Bioaugmentation to anodic microflora with anaerobic culture
      documented enhanced electrogenic activity at OL4 operation. Voltammetric
      profiles, Tafel analysis and VFA generation were in agreement with the observed
      power generation and degradation efficiency.

PMID- 22366610
TI  - Improvement of biomass properties by pretreatment with ionic liquids for
      bioconversion process.
AB  - Cassava pulp residue and rice straw were used as a precursor for pretreatment
      with ionic liquids to study the effects of pretreatment conditions on product
      yield and properties. Cassava pulp residue is a potential biomass in the
      bioconversion process due to it requiring mild pretreatment conditions while
      providing a high sugar conversion. The maximum sugar conversion and lignin
      extraction are attained from pretreatment of biomasses with particle size of <38
      MUm and ionic liquid of 1-Ethyl-3-methylimidazolium acetate at 120 degrees C for
      24h. The effectiveness of ionic liquid for biomass pretreatment process follows
      the sequence: 1-Ethyl-3-methylimidazolium acetate>1-Ethyl-3-methylimidazolium
      diethyl phosphate>1,3-Dimethylimidazolium methyl sulfate. The increase of
      pretreatment temperature from 25 to 120 degrees C and decrease of biomass
      particle size renders higher sugar conversion, lignin extraction and lower
      crystallinity index. However, pretreatment at temperatures higher than 120
      degrees C shows a sharp decline of regenerated biomass yield, sugar conversion
      and lignin extraction and giving higher crystallinity index at pretreatment
      temperature of 180 degrees C.

PMID- 22366611
TI  - Acetone, butanol, and ethanol production from wastewater algae.
AB  - Acetone, butanol, and ethanol (ABE) fermentation by Clostridium
      saccharoperbutylacetonicum N1-4 using wastewater algae biomass as a carbon source
      was demonstrated. Algae from the Logan City Wastewater Lagoon system grow
      naturally at high rates providing an abundant source of renewable algal biomass.
      Batch fermentations were performed with 10% algae as feedstock. Fermentation of
      acid/base pretreated algae produced 2.74 g/L of total ABE, as compared with 7.27
      g/L from pretreated algae supplemented with 1% glucose. Additionally, 9.74 g/L of
      total ABE was produced when xylanase and cellulase enzymes were supplemented to
      the pretreated algae media. The 1% glucose supplement increased total ABE
      production approximately 160%, while supplementing with enzymes resulted in a
      250% increase in total ABE production when compared to production from pretreated
      algae with no supplementation of extraneous sugar and enzymes. Additionally,
      supplementation of enzymes produced the highest total ABE production yield of
      0.311 g/g and volumetric productivity of 0.102 g/Lh. The use of non-pretreated
      algae produced 0.73 g/L of total ABE. The ability to engineer novel methods to
      produce these high value products from an abundant and renewable feedstock such
      as algae could have significant implications in stimulating domestic energy
      economies.

PMID- 22366612
TI  - Oil production by the yeast Trichosporon dermatis cultured in enzymatic
      hydrolysates of corncobs.
AB  - Corncob was hydrolyzed with Trichoderma reesei cellulase and used as substrate
      for growth by the oleaginous yeast Trichosporon dermatis without detoxification
      or addition of a nitrogen source or trace elements. A total biomass of 24.4g/L
      with a lipid content of 40.1% (corresponding to a lipid yield of 9.8g/L), and a
      high lipid coefficient (lipid yield per mass of sugar, %g/g) of 16.7 could be
      achieved after cultivation for 7days. Therefore, T. dermatis is a promising
      strain for microbial oil production from lignocellulosic biomass.

PMID- 22366613
TI  - Optical and photoconductivity spectra of novel Ag2In2SiS6 and Ag2In2GeS6
      chalcogenide crystals.
AB  - Complex spectral studies of near-band gap and photoconductive spectra for novel
      Ag(2)In(2)SiS(6) and Ag(2)In(2)GeS(6) single crystals are presented. The spectral
      dependences of photoconductivity clearly show an existence of spectral maxima
      within the 450 nm-540 nm and 780 nm-920 nm. The fundamental absorption edge is
      analyzed by Urbach rule. The origin of the spectral photoconductivity spectral
      maxima is discussed. Temperature dependences of the spectra were done. The
      obtained spectral features allow to propose the titled crystals as photosensors.
      An analysis of the absorption and photoconductivity spectra is given within a
      framework of oversimplified spectroscopic model of complex chalcogenide crystals.

PMID- 22366614
TI  - Structural and spectroscopic characterization of 2-mesityl-1H-benzo[d]imidazol-3
      ium chloride: a combined experimental and theoretical analysis.
AB  - The title molecular salt, 2-mesityl-1H-benzo[d]imidazol-3-ium chloride
      (C(16)H(17)N(2)(+).Cl-), was synthesized unexpectedly from the reaction of N
      [(1E)-mesitylmethylene]benzene-1,2-diamine and CoCl(2).6H(2)O, and characterized
      by elemental analysis, (1)H NMR and FT-IR spectroscopies, and single-crystal X
      ray diffraction technique. In addition, quantum chemical calculations employing
      density functional theory (DFT) method with the 6-311++G(d,p) basis set were
      performed to study the molecular, spectroscopic and some electronic structure
      properties of the title compound, and the results were compared with the
      experimental findings. The computational result shows that the optimized geometry
      can well reproduce the crystal structural parameters. The intermolecular proton
      transfer process between the ionic (C(16)H(17)N(2)(+).Cl-) and nonionic forms
      (C(16)H(16)N(2).HCl) of the title salt is investigated and found to be almost
      barierless with an energy value of 0.20 kcal mol(-1). The NLO properties of the
      compound are bigger than those of urea.

PMID- 22366615
TI  - Two one-dimensional d10-metal coordination polymers based on polydentate Schiff
      base ligand: synthesis, crystal structure and luminescent properties.
AB  - Two one-dimensional d(10)-metal coordination polymers
      {[AgL(H(2)O)](2)[AgL(NO(3))](2)(NO(3))(2)L(H(2)O)(2)}(n) (1) and [ZnLCl(2)](n)
      (2) (L=N,N'-bis-(1-pyridin-4-yl-ethylidene)-hydrazine) have been synthesized and
      characterized by IR, elemental analysis, TG technique, XRPD and X-ray
      crystallography. Polymer 1 contains two types of 1D Ag-double-chain units. Ag(1)
      double-chain unit is formed by linking two adjacent Ag(1)-L-chains through face
      to-face pi?pi interactions, while Ag(2)-double-chain unit is formed through the
      combination of coordinating NO(3)(-) anions bridging interactions and pi?pi
      interactions between two adjacent Ag(2)-L-chains. Free ligands interact with the
      adjacent Ag(1)-double-chain units and Ag(2)-double-chain units to form a 3D
      supramolecular structure through multiform hydrogen bonds. For polymer 2, each
      ligand acts as a bis-monodentate bridging ligand to bind adjacent Zn(II) centers
      forming a one-dimensional chain structure. Furthermore, 1D chain is held together
      with its neighboring ones via CH?pi interactions. The luminescent properties of
      the polymers 1 and 2 were investigated in the solid state at room temperature.

PMID- 22366616
TI  - Study of coal and graphite specimens by means of Raman and cathodoluminescence.
AB  - The weak luminescence shown by coals has been attributed to accessorial minerals
      and poly-nuclear aromatic hydrocarbons, such as exinite, vitrinite or inertinite,
      while the luminescence quenching has been found in asphaltenes produced by coal
      hydrogenation or in pyridine extracts. Nowadays, the spatial resolution and the
      improved luminescence efficiency of the modern spectrometers allow some details
      of the luminescent emission centers to be explained. We have selected museum
      historical coal specimens with different rank, i.e., peat, lignite, sub
      bituminous, bituminous, and anthracite to be analyzed by their spectra from
      cathodoluminescence probe (CL) of an environmental scanning electron microscopy
      (ESEM), with an energy dispersive spectrometry analyzer (EDS). Additional
      analytical controls were also performed by X-ray diffraction (XRD), X-ray
      fluorescence (XRF) and Raman spectrometries. We conclude that coals may display
      different luminescence emission features coming from several different sources,
      as follows: (i) broadband of intense luminescence from polynuclear aromatic
      hydrocarbons, (ii) weakly visible broadband luminescence attributed to band-tail
      states caused by variations in the energy gap of individual sp(2) carbon
      clusters, which are different in size and/or shape, (iii) silicate impurities
      causing the common luminescence peak at 325 nm observed in coals. This peak is
      due to non-bridging oxygen hole centres (=Si-O.) probably generated by precursor
      Si-O-C species formed by =Si-O. defects and carbon atoms; (iv) a 710 nm CL
      emission commonly detected also in wood and ivory, which has been correlated with
      hydrocarbon groups of chlorophyll or lignine. Coals are very complex rocks,
      composed by both organic and inorganic phases with variable and complex spectra.
      More analyses are necessary and carbonaceous standards of graphite, silicon
      carbide, stuffed carbon silica and diamond at variable experimental conditions
      have to be developed.

PMID- 22366617
TI  - "Additive" cooperativity of hydrogen bonds in complexes of catechol with proton
      acceptors in the gas phase: FTIR spectroscopy and quantum chemical calculations.
AB  - Experimental study of hydrogen bond cooperativity in hetero-complexes in the gas
      phase was carried out by IR-spectroscopy method. Stretching vibration frequencies
      of O-H groups in phenol and catechol molecules as well as of their complexes with
      nitriles and ethers were determined in the gas phase using a specially designed
      cell. O-H groups experimental frequency shifts in the complexes of catechol
      induced by the formation of intermolecular hydrogen bonds are significantly
      higher than in the complexes of phenol due to the hydrogen bond cooperativity. It
      was shown that the cooperativity factors of hydrogen bonds in the complexes of
      catechol with nitriles and ethers in the gas phase are approximately the same.
      Quantum chemical calculations of the studied systems have been performed using
      density functional theory (DFT) methods. It was shown, that theoretically
      obtained cooperativity factors of hydrogen bonds in the complexes of catechol
      with proton acceptors are in good agreement with experimental values. Cooperative
      effects lead to a strengthening of intermolecular hydrogen bonds in the complexes
      of catechol on about 30%, despite the significant difference in the proton
      acceptor ability of the bases. The analysis within quantum theory of atoms in
      molecules was carried out for the explanation of this fact.

PMID- 22366618
TI  - Molecular structure (monomeric and dimeric structure) and HOMO-LUMO analysis of 2
      aminonicotinic acid: a comparison of calculated spectroscopic properties with FT
      IR and UV-vis.
AB  - The experimental (UV-vis and FT-IR) and theoretical study of 2-aminonicotinic
      acid (C(6)H(6)N(2)O(2)) was presented in this work. The ultraviolet absorption
      spectrum of title molecule that dissolved in ethanol and water were examined in
      the range of 200-400 nm. The FT-IR spectrum of the title molecule in the solid
      state were recorded in the region of 400-4000 cm(-1). The geometrical parameters
      and energies of 2-aminonicotinic acid have been obtained for all four
      conformers/isomers (C1, C2, C3, C4) from DFT (B3LYP) with 6-311++G(d,p) basis set
      calculations. C1 form has been identified the most stable conformer due to
      computational results. Therefore, spectroscopic properties have been searched for
      the most stable form of the molecule. The vibrational frequencies were calculated
      and scaled values were compared with experimental FT-IR spectrum. The complete
      assignments were performed based on the total energy distribution (TED) of the
      vibrational modes, calculated with scaled quantum mechanics (SQM) method. Also
      the molecular structures, vibrational frequencies, infrared intensities were
      calculated for a pair of molecules linked by the intermolecular O-H?O hydrogen
      bond. Moreover, the thermodynamic properties of the studied compound at different
      temperatures were calculated. Besides, charge transfer occurring in the molecule
      between HOMO and LUMO energies, frontier energy gap, molecular electrostatic
      potential (MEP) were calculated and presented. The spectroscopic and theoretical
      results are compared to the corresponding properties for monomer and dimer of C1
      conformer. The optimized bond lengths, bond angles, calculated frequencies and
      electronic transitions showed the agreement with the experimental results.

PMID- 22366619
TI  - DFT study of structure, IR and Raman spectra of the first generation dendron
      built from cyclotriphosphazene core with terminal carbamate and ester groups.
AB  - The FTIR and FT-Raman spectra of the first generation dendron built from the
      cyclotriphosphazene core, five arms -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds on the
      righthand side with ten carbamate terminal groups and one ester function G(v1)
      have been recorded. The IR and Raman spectra of the zero generation dendron G(v0)
      and first generation dendrimer G(1) with the same core and terminal groups were
      also examined. The structural optimization and normal mode analysis were
      performed for dendron G(v1) on the basis of the density functional theory (DFT).
      The calculated geometrical parameters and harmonic vibrational frequencies are
      predicted in a good agreement with the experimental data. It was found that G(v1)
      has a concave lens structure with planar -O-C(6)H(4)-CH=N-N(CH(3))-P(S) 2 bonds
      on the righhand side fragments and slightly non-planar cyclotriphosphazene core.
      The carbamate groups attached to different arms show significant deviations from
      a symmetrical arrangement relative to the local planes of repeating units. The
      experimental IR spectrum of G(v1) dendron was interpreted by means of potential
      energy distributions. The strong band 1604 cm(-1) shows marked changes of the
      optical density in dependence of the carbamate, ester or azomethyne substituents
      in the aromatic ring. The frequencies of nu(N-H) and nu(C=O) bands in the IR
      spectra reveal the presence of the different types of H-bonds in the studied
      dendrimers.

PMID- 22366620
TI  - Solvent dependent Raman bandshape analysis on CO containing molecules:
      vibrational relaxation study.
AB  - Solvent dependent Raman band studies of some carbonyl containing molecules have
      been carried out in chlorobenzene (CLB) and chloroform (CLF) solvents. The
      variation of bandwidth with the solvent concentration was discussed using
      different mechanisms. The vibrational and reorientational correlation times were
      studied corresponding to solvent concentrations. The reorientational correlation
      time follows with the liquid viscosity in molecules under study. It reflects
      about the nature of solvent molecules hindering to the orientational motion of
      solute in liquid solution.

PMID- 22366621
TI  - Study on the interaction between NCP-(4-hydroxycoumarins) and bovine serum
      albumin by spectroscopic techniques.
AB  - The interaction between N-confused porphyrins-(4-hydroxycoumarins) diad (NCP-(4
      hydroxycoumarins)) and bovine serum albumin (BSA) was studied using fluorescence
      and ultraviolet spectroscopy at different temperatures under imitated
      physiological conditions. The experimental results showed that the fluorescence
      of BSA was quenched by NCP-(4-hydroxycoumarins) through a combined quenching
      procedure. The binding constants, binding sites and corresponding thermodynamic
      parameters between NCP-(4-hydroxycoumarins) and BSA at different temperatures
      were obtained. According to Forster non-radiation energy transfer theory, the
      binding distance between BSA and NCP-(4-hydroxycoumarins) was calculated to be
      about 2.1 nm. The effect of NCP-(4-hydroxycoumarins) on the conformation of BSA
      was analyzed using synchronous fluorescence spectroscopy. In addition, the effect
      of some metal ions Cu(2+), Ca(2+), Mg(2+), and Ni(2+) on the binding constant
      between NCP-(4-hydroxycoumarins) and BSA was examined.

PMID- 22366622
TI  - Theoretical and experimental study on the excited states of the X-, alpha- and
      beta-forms of lithium phthalocyanine.
AB  - The electronic structures and absorption spectra for three different types (X,
      alpha and beta) of model dimers of lithium phthalocyanine (LiPc) were
      investigated by the density functional theory (DFT) and compared with a LiPc
      monomer. We quantitatively investigated the excited states of the three LiPc
      dimers using time-dependent DFT calculations. The differences and similarities of
      the observed absorption spectra in the solution and the polymorphic solids of
      LiPc were clearly interpreted by the calculated excited states of the monomer and
      dimers. The calculated results for the dimers presumed that the X-form showed a
      different electronic spectral pattern from the monomer and the other two forms,
      whereas the alpha- and beta-forms presented similar electronic absorption
      profiles to each other and to the monomer. The calculated excited states also
      explained the differences in absorption profiles between LiPc and typical
      phthalocyanine compounds. These characteristic features of LiPc would be closely
      related to its molecular orbitals, especially those which originated from the
      singly occupied molecular orbital (SOMO) of the LiPc monomer. It was shown that
      the next highest occupied pi-type orbital to the SOMO of the monomer reduced the
      energy of the low-lying excited states, which corresponded to the Q- and B-bands
      of the dimers.

PMID- 22366623
TI  - Platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo [1,5-a]pyrimidines:
      spectroscopical characterization and cytotoxic activity in vitro.
AB  - Complexes of the types: cis-[PtI(2)(dptp)(2)] (1), cis-[PtI(2)(NH(3))(dptp)] (2),
      trans-[PtI(2)(dptp)(dmso)] (3) and trans-[PtI(2)(dbtp)(dmso)] (4), where dptp=5,7
      diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), dbtp=5,7-ditertbutyl-1,2,4
      triazolo[1,5-a]pyrimidine have been synthesized and characterized by infrared and
      multinuclear magnetic resonance spectroscopic techniques ((1)H, (13)C, (15)N,
      (195)Pt). In (195)Pt NMR, the cis-diiodo complexes were observed between -2601
      ppm and -3261 ppm, while the trans coordination compounds were found at higher
      field (ca. -4389 ppm). In all cases significant (15)N NMR shielding (92-95 ppm)
      were observed for N(3) atom indicating this nitrogen atom as a coordination site.
      The cis complexes have been assayed for antitumor activity in vitro against two
      human cell lines: A549 (non-small cell lung carcinoma) and T47D (breast cancer).
      The results indicate a moderate antiproliferative activity of (2) against human
      cancer lines.

PMID- 22366624
TI  - Citrate-capped Mn-modified CdSe/CdS quantum dots as luminescent probes for
      levodopa detection in aqueous solution.
AB  - A novel kind of citrate capped Mn-modified CdSe/CdS quantum dots (QDs) was
      developed. The Mn-modified CdSe/CdS QDs had a narrow, symmetric emission and
      strong fluorescence with quantum yield over 41%. The interaction between the QDs
      and levodopa was investigated. The results showed that levodopa selectively
      quenched the fluorescence intensity of the QDs. Based on the fluorescence
      quenching of the synthesized QDs by levodopa, a simple, rapid and specific
      quantitative method for levodopa was proposed. The factors affecting the
      fluorescence detection for levodopa were studied. Under the optimum conditions,
      the quenched intensity of the fluorescence versus levodopa concentration from 1
      to 100 MUM gave a linear response with an excellent correlation coefficient of
      0.9996, and the limit of detection (3sigma/K) was 2 * 10(-7)M. The contents of
      levodopa in pharmaceutical tablets were determined by the proposed method and the
      results agreed with the claimed values.

PMID- 22366625
TI  - Psychometric properties of the Chinese Breast Cancer Screening Beliefs
      questionnaire.
AB  - BACKGROUND: Breast cancer is the most common type of cancer in women. The Chinese
      Breast Cancer Screening Beliefs (CBCSB) questionnaire was developed to measure
      Chinese-Australian women's beliefs, knowledge and attitudes about breast cancer
      and breast cancer screening. PURPOSE: To assess the psychometrics of the modified
      version CBCSB in a Chinese-speaking community. METHODS: Two items in the original
      CBCSB were removed because they were not applicable to the Hong Kong setting,
      which resulted in an 11-item CBCSB. A total of 730 women aged at least 18 years
      old without a history of breast cancer self-completed the questionnaire. RESULTS:
      Based on 730 Chinese-speaking women with mean age of 43 years, the three
      hypothesized subscales of the CBCSB had Cronbach's alpha ranging between 0.69 and
      0.75. Non-responses to the items were at most only 3.3%. The corrected item-total
      correlations for the hypothesized subscales ranged from 0.35 to 0.63 and were
      higher than those for the competing subscales. As hypothesized, the frequency of
      health practices was significantly associated with all subscales of the CBCSB.
      Confirmatory factor analysis showed an adequate fit for the hypothesized three
      factor structure of the modified CBCSB questionnaire. CONCLUSIONS: The 11-item
      CBCSB questionnaire was culturally appropriate, reliable and valid in a Chinese
      speaking community setting. It can be used to gain understanding of Chinese
      speaking women's beliefs, knowledge and attitudes about breast cancer and breast
      cancer screening. It may also serve as an outcome for the development and
      assessment of public education programs for breast cancer screening.

PMID- 22366626
TI  - People with intellectual disabilities who are affected by a relative or friend
      with cancer: a qualitative study exploring experiences and support needs.
AB  - PURPOSE: To explore the experiences of people with intellectual disabilities (ID)
      who have a relative or friend with cancer, and to identify their support needs.
      METHODS AND SAMPLE: Participants were 21 adults with ID who had a relative/friend
      with cancer, now or in the past. Data were collected using focus groups and face
      to-face interviews. Focus groups met four times, using a range of data collection
      techniques. Sessions were audio recorded and transcribed verbatim. Data were
      analysed using thematic content analysis. Data were collected between March 2010
      and March 2011. RESULTS: Four themes emerged: (1) Protection and inclusion:
      participants who had not been told about their loved one's illness felt excluded;
      (2) Coping with cancer: participants had vivid memories of events and feelings.
      They worried about their families. Many had become carers themselves; (3)
      Understanding cancer: participants lacked knowledge about cancer and wanted to
      know more. (4) Someone to talk to: participants would have liked to share their
      feelings and questions with family, friends or professionals, but had not voiced
      their questions or concerns. 'Someone to talk to about my feelings and worries'
      and 'Someone to support the rest of my family' were voted the most helpful
      support strategies. CONCLUSIONS: Cancer nurses should ensure that people with ID
      in their patients' social circle are included in the family unit and receive
      adequate emotional support. They should be proactive in giving them information
      that is easy to understand. Using fictional stories can be particularly helpful
      in eliciting questions and concerns.

PMID- 22366630
TI  - Evaluation for ulnar neuropathy at the elbow in Ironman triathletes: physical
      examination and electrodiagnostic evidence.
AB  - OBJECTIVE: Evaluation of the elbow in Ironman triathletes for ulnar compression
      neuropathy caused by aerobar use. DESIGN: Descriptive laboratory study. SETTING:
      Ironman California 70.3, Ironman Arizona, Ironman New Orleans 70.3, San Antonio,
      Texas. PARTICIPANTS: Study 1: (n = 712) Ironman California 70.3/Ironman Arizona
      participants. Study 2: (n = 54) Ironman New Orleans 70.3 finishers. Study 3: (n =
      11) participants training for an Ironman triathlon. INTERVENTIONS: Pilot
      questionnaire (study 1). Pilot questionnaire and prerace and postrace physical
      examination (study 2). Pilot questionnaire and preride and postride (and
      postseason) physical examination, and electrodiagnostic testing (study 3). MAIN
      OUTCOME MEASURES: Participants with symptoms, physical examination findings, and
      electrodiagnostic findings (amplitude or conduction velocity decrease) (P <
      0.05). RESULTS: In study 1, 20.8% reported a history of ulnar symptoms. In study
      2, 35.2% reported a history of ulnar symptoms. Preevent physical examination
      testing of the elbow showed 39.5% with positive Tinel sign and 41.5% with
      positive flexion/compression test. Postevent testing showed 70.4% with positive
      Tinel sign and 75.9% with positive flexion/compression test. In study 3, 46%
      reported ulnar symptoms. Preride physical examination testing showed 4.5% with
      positive Tinel sign and 9% with positive flexion/compression test. Postride
      testing showed 95.5% with positive Tinel sign and 91% with positive
      flexion/compression test. Postseason testing showed 64% with positive Tinel sign
      and 82% with positive flexion/compression test. Electrodiagnostic testing
      comparing preride and postride showed that ulnar nerve latency increased in 82%,
      amplitude decreased in 50%, and conduction velocity slowed in 64%.
      Electrodiagnostic testing comparing preseason and postseason showed that ulnar
      nerve latency increased in 73%, amplitude decreased in 64%, and conduction
      velocity slowed in 82%. CONCLUSIONS: The findings support the hypothesis of an
      ulnar compression neuropathy at the elbow occurring at high rates in aerobar
      using Ironman triathletes.

PMID- 22366631
TI  - An unusual mechanism for injury of the anterior cruciate ligament in figure
      skating.
AB  - A 20-year-old competitive figure skater presented with an acute disabling knee
      injury that occurred in the overhead, non-weight-bearing knee during the
      performance of a Biellmann spin. Examination and magnetic resonance imaging
      confirmed the diagnosis of a complete anterior cruciate ligament (ACL) tear. To
      our knowledge, no previous cases of acute injury of the ACL sustained during the
      execution of a Biellmann spin have been reported. The ACL injury we report is
      unique because it occurred without the blade contacting the ice. The mechanism of
      injury has some features that are similar to those of other noncontact ACL
      injuries, with the addition of centrifugal force as a potential contributor to
      the injury.

PMID- 22366632
TI  - Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody
      hapten complex: rapid and robust IgG response induced by a single subcutaneous
      injection.
AB  - Producing diagnostic antibodies in chicken egg yolk represents an alternate
      animal system that offers many advantages including high productivity at low
      cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG
      from yolk still represents an underused resource. The potential of agonistic
      monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has
      been demonstrated in mammals, but not in chickens. We recently reported an
      agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have
      potential as an immunological adjuvant. In this study, we examined the efficacy
      of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting
      cells (APCs)] in enhancing an effective IgG response in chickens. For this
      purpose, an immune complex consisting of one streptavidin molecule, two
      directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide
      molecules was produced. Chickens were immunized subcutaneously with doses of this
      complex ranging from 10 to 90 MUg per injection once, and relative quantification
      of the peptide-specific IgG response showed that the mAb 2C5-based complex was
      able to elicit a strong IgG response as early as four days post-immunization.
      This demonstrates that CD40-targeting antigen to chicken APCs can significantly
      enhance antibody responses and induce immunoglobulin isotype-switching. This
      immunization strategy holds promise for rapid production of hapten-specific IgG
      in chickens.

PMID- 22366633
TI  - Pitfalls in anti-influenza T cell detection by Elispot using thimerosal
      containing pandemic H1N1 vaccine as antigen.
AB  - Monitoring T cells in combination with humoral response may be of value to
      predict clinical protection and cross-protective immunity after influenza
      vaccination. Elispot technique which measures cytokine produced after antigen
      specific T cell stimulation is used routinely to detect and characterize anti
      viral T cells. We found that the preservative thimerosal present in most H1N1
      pandemic vaccines, induced in vitro abortive activation of T cells followed by
      cell death leading to false-positive results with the Elispot technique. The size
      of the spots, usually not measured in routine analysis, appears to be a
      discriminative criterion to detect this bias. Multi-dose vials of vaccine
      containing thimerosal remain important for vaccine delivery and our results alert
      about false-positive results of Elispot to monitor the clinical efficacy of these
      vaccines. We showed that this finding extends for other T cell monitoring
      techniques based on cytokine production such as ELISA. Although measuring in
      vitro immune response using the whole vaccine used for human immunization
      directly reflects in vivo global host response to the vaccine, the present study
      strongly supports the use of individual vaccine components for immune monitoring
      due to the presence of contaminants, such as thimerosal, leading to a bias in
      interpretation of the results.

PMID- 22366634
TI  - Acute phase response following intravenous zoledronate in postmenopausal women
      with low bone mass.
AB  - An acute phase response (APR) is frequently observed in patients treated with
      intravenous (i.v.) zoledronate (ZOL). We aimed to define clinical and laboratory
      parameters that may predict ZOL-induced APR in women with low bone mass. Fifty
      one postmenopausal women with low bone mass were given a single i.v. infusion of
      ZOL 5mg. APR was clinically defined by the visual analog pain scale (VAS) for the
      musculoskeletal symptoms and body temperature. White blood cell count (WBC),
      leucocyte subpopulations, C-reactive protein (CRP), parathyroid hormone (PTH), 25
      hydroxyvitamin D [25(OH)D], interleukins (IL)-1b and -6, tumor necrosis factor
      (TNF)alpha and interferon (IFN)gamma were measured before and 48 h following the
      infusion. Subsequently, patients were divided into those experiencing APR (APR+)
      or not (APR-). WBC, granulocytes, CRP, IL-1b and IL-6 were significantly
      increased, whereas lymphocytes, eosinophils, calcium, phosphate and 25(OH)D
      decreased 48h after ZOL infusion. Twenty-eight of the 51 patients (54.9%)
      experienced an APR. APR+ patients were younger and had higher baseline
      lymphocytes compared to APR- patients. There was no difference (p=0.405) in the
      development of APR between treatment-naive patients (19/32, 59.4%) and patients
      previously treated with another oral nitrogen-containing bisphosphonate (9/19,
      47.4%). In conclusion, our data suggest that pre-treatment higher lymphocyte
      number increases the risk of APR while previous treatment with another nitrogen
      containing bisphosphonate does not significantly reduce the risk. Serum 25(OH)D
      concentrations decrease significantly after the infusion, possibly as part of the
      inflammatory response to ZOL.

PMID- 22366635
TI  - High resolution electron backscatter diffraction measurements of elastic strain
      variations in the presence of larger lattice rotations.
AB  - In this paper we explore methods of measuring elastic strain variations in the
      presence of larger lattice rotations (up to -11 degrees ) using high resolution
      electron backscatter diffraction. We have examined the fundamental equations
      which relate pattern shifts to the elastic strain tensor and modified them to a
      finite deformation framework from the original infinitesimal deformation one. We
      incorporate the traction free boundary condition into the minimisation problem
      for the finite deformation case (i.e. large rotations and small elastic strains).
      Numerical experiments show that this finite deformation kinematic analysis
      continues to work well, while the infinitesimal analysis fails, when the
      misorientation between test and reference pattern is made increasingly high.
      However, measurements on patterns simulated using dynamical diffraction theory
      indicated that this formulation is not sufficient to recover elastic strains
      accurately because the pattern shifts are not determined accurately when large
      rotations are present. To overcome this issue we remap the test pattern to an
      orientation that is close to that of reference pattern. This remapping was
      defined by a finite rotation matrix, which was estimated from the infinitesimal
      rotation matrix measured using cross-correlation. A second cross-correlation
      analysis between the reference pattern and the remapped test pattern allows the
      elastic strains to be recovered using the much simpler infinitesimal deformation
      theory. We have also demonstrated that accurate recovery of elastic strains
      requires accurate knowledge of the pattern centre if this remapping algorithm is
      used.

PMID- 22366636
TI  - Substrate specificity screening of oat (Avena sativa) seeds aminopeptidase
      demonstrate unusually broad tolerance in S1 pocket.
AB  - Aminopeptidases are proteolytic enzymes that remove one amino acid at a time from
      N-terminus of peptidic substrates. In plants, inhibitors of aminopeptidases can
      find potential applications in agriculture as herbicides. In this report we have
      used a library of fluorogenic derivatives of natural and unnatural amino acids
      for substrate specificity profiling of oat (Avena sativa) aminopeptidase.
      Interestingly, we have found that this enzyme recognizes effectively among the
      natural amino acids basic residues like Arg and Lys, hydrophobic Phe, Leu and
      Met, but also to some extent acidic residues Asp and Glu. In the case of
      unnatural amino acids hydrophobic residues (hPhe and hCha) and basic hArg were
      preferentially recognized.

PMID- 22366637
TI  - Temporal accumulation of salicylic acid activates the defense response against
      Colletotrichum in strawberry.
AB  - Many authors have reported interactions between strawberry cultivars and
      pathogenic microorganisms, yet little is known about the mechanisms triggered in
      the plant. In this paper we examine the participation of the salicylic acid (SA)
      signaling pathway involved in the response of Fragaria x ananassa cv. Pajaro
      plants to pathogens. Strawberry plants were challenged with the virulent strain
      M11 of Colletotrichum acutatum, or with the avirulent strain M23 of
      Colletotrichum fragariae which confers resistance to the former. Our study showed
      that the isolate M23 induced a temporal SA accumulation that was accompanied with
      the induction of PR-1 gene expression in strawberry plants. Such events occured
      after the oxidative burst, evaluated as the accumulation of hydrogen peroxide and
      superoxide anion, and many hours before the protection could be detected. Similar
      results were obtained with exogenously applied SA. Results obtained supports the
      hypothesis that strawberry plants activate a SA mediated defense mechanisms that
      is effective against a causal agent of anthracnose. In contrast, plants
      inoculated with M11 did not show oxidative burst, SA accumulation or PR1 gene
      induction. This is the first report about a defense response signaling pathway
      studied in strawberry plants.

PMID- 22366639
TI  - Changes in beclin-1 and micro-calpain expression in tri-ortho-cresyl phosphate
      induced delayed neuropathy.
AB  - Tri-ortho-cresyl phosphate (TOCP) can cause toxic neuropathy known as
      organophosphate-induced delayed neuropathy (OPIDN), which is pathologically
      characterized by the swollen axon containing aggregations of neurofilaments,
      microtubules, and multivesicular vesicles. Autophagy is a self-degradative
      process which plays a housekeeping role in removing misfolded proteins and
      damaged organelles. The current study was designed to investigate the possible
      roles of autophagy in the pathogenesis of OPIDN. Adult hens were treated with a
      dose of 750mg/kg TOCP by gavage, or injected subcutaneously with 60mg/kg
      phenylmethanesulfonyl fluoride (PMSF) dissolved in DMSO 24h earlier and
      subsequently treated with TOCP, then sacrificed on the time-points of 0, 1, 5,
      10, and 21 days after dosing of TOCP respectively. The levels of beclin-1 and MU
      calpain in tibial nerves and spinal cords were determined by immunoblotting. The
      results showed that in both tissues TOCP increased the expression of MU-calpain
      while decreased that of beclin-1. When given before TOCP administration, PMSF
      pretreatment could protect hens against the delayed neuropathy. In the meantime,
      pretreatment with PMSF reduced calpain expression below basal and increased
      beclin-1 expression above basal in tibial nerve, whereas it simply returned
      calpain and beclin-1 expression to their basal levels in spinal cord. In
      conclusion, the intoxication of TOCP was associated with a significant change of
      beclin-1 in hen nervous tissues, which suggested that disruption of autophagy
      regulated machinery in neurons might be involved in the pathogenesis of OPIDN.

PMID- 22366638
TI  - Use of a polyanionic carbomer, Carbopol971P, in combination with MF59, improves
      antibody responses to HIV-1 envelope glycoprotein.
AB  - Identification of optimal antigen(s) and adjuvant combination(s) to elicit
      potent, protective, and long-lasting immunity has been a major challenge for the
      development of effective vaccines against chronic viral pathogens, such as HIV-1,
      for which there are not yet any licensed vaccines. Here we describe the use of a
      novel adjuvant approach employing Carbopol 971P((r)) NF (hereafter referred to as
      Carbopol971P), a cross-linked polyanionic carbomer, in combination with the
      Novartis proprietary oil-in-water adjuvant, MF59, as a potentially safe and
      effective adjuvant to augment humoral immune responses to the HIV-1 envelope
      glycoprotein (Env). Intramuscular immunization of small animals with recombinant
      Env glycoprotein (gp140) formulated in Carbopol971P plus MF59 gave significantly
      higher titers of binding and virus neutralizing antibodies as compared to
      immunization using gp140 with either MF59 or Carbopol971P alone. In addition, the
      antibodies generated were of higher avidity. Importantly, the use of Carbopol971P
      plus MF59 did not cause any serious adverse reactions or any obvious health
      problems in animals upon intramuscular administration. Hence, the Carbopol971P
      plus MF59 adjuvant formulation may provide a benefit for future vaccine
      applications.

PMID- 22366640
TI  - Integration of ethnic food into Swedish food rituals. The cultural fitness of
      tacos.
AB  - This paper explores the meaning of the Mexican dish tacos for Swedish consumers.
      As such, this study examines the relationship between ethnic food and food
      culture in light of contemporary changing food rituals. The results reveal that
      the Swedish food ritual of Friday dinner can be enacted through eating tacos.
      Friday dinner is a point in time and space at which family members gather, after
      a busy week following divergent schedules that keep them from eating together,
      and to which children's food preferences are central. Tacos fulfil all the
      requirements for a quick-to-cook yet social dish that enables hardworking but
      time-constrained families to eat together. The much-debated informal and
      fragmented character of food consumption in contemporary society is accommodated
      in the taco meal.

PMID- 22366641
TI  - Relationships between appetite and quality of life in hemodialysis patients.
AB  - The aim of this paper was to investigate the association between appetite and
      kidney-disease specific quality of life in maintenance hemodialysis patients.
      Quality of life (QoL) was measured using the kidney disease quality of life
      survey. Appetite was measured using self-reported categories and a visual analog
      scale. Other nutritional parameters included Patient-Generated Subjective Global
      Assessment (PGSGA), dietary intake, body mass index and biochemical markers C
      reactive protein and albumin. Even in this well nourished sample (n=62) of
      hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations
      (r=0.420) and body mass index (r=-0.409) were all significantly associated with
      the physical health domain of QoL. As self-reported appetite declined, QoL was
      significantly lower in nine domains which were mostly in the SF36 component and
      covered social functioning and physical domains. Appetite and other nutritional
      parameters were not as strongly associated with the Mental Health domain and
      Kidney Disease Component Summary Domains. Nutritional parameters, especially
      PGSGA score and appetite, appear to be important components of the physical
      health domain of QoL. As even small reductions in nutritional status were
      associated with significantly lower QoL scores, monitoring appetite and
      nutritional status is an important component of care for hemodialysis patients.

PMID- 22366642
TI  - The use of nonnutritive sucking to facilitate oral feeding in a term infant: a
      single case study.
AB  - This individual case study presents an evaluation of and reflection on the use of
      nonnutritive sucking as a technique to facilitate nutritive sucking with an
      infant with feeding difficulties. Nonnutritive sucking is used in a variable way
      with mainly premature or sick infants. However, the rationale underpinning use of
      such an approach is not clear. The infant participant in this study, Baby H, was
      born at 37 weeks. This case illustrates the use of nonnutritive sucking as an
      approach with supported rationales for promoting transition toward oral feeding
      with infants who have complex needs and who are term infants. The literature
      focuses on using nonnutritive sucking with premature infants who have no
      additional difficulties such as hypoxic neonatal encephalopathy, meconium
      aspiration, sepsis, or severe perinatal asphyxia. The intervention carried out
      with Baby H demonstrates that nonnutritive sucking can contribute toward the
      management of an infant's feeding development. Baby H took 23 days to develop a
      sequential nonnutritive sucking pattern, but her ability to transfer this to
      nutritive sucking and safe feeding took the first 17 months of this infant's
      life. This study is unique in that it explored the issues involved with a term
      infant who had complex needs that impacted on feeding development. It is
      important because many practitioners use nonnutritive sucking with infants who
      have complex needs.

PMID- 22366643
TI  - Glucose-dependent insulinotropic peptide impairs insulin signaling via inducing
      adipocyte inflammation in glucose-dependent insulinotropic peptide receptor
      overexpressing adipocytes.
AB  - Glucose-dependent insulinotropic peptide (GIP) exerts multiple biological effects
      via the G-protein-coupled receptor GIPR, including glucose-stimulated insulin
      production and secretion, cell proliferation, and antiapoptosis in pancreatic
      beta-cells. In an obese state, the circulating level of GIP is elevated. GIPR
      knockout mice are resistant to high-fat-diet-induced obesity. The rising evidence
      suggests a potential role of GIP in adipocyte biology and lipid metabolism. In
      our study, we overexpressed GIPR in 3T3-L1 CAR adipocytes and demonstrated that
      GIP impaired the physiological functions of adipocytes as a consequence of
      increased production of inflammatory cytokines and chemokines and phosphorylation
      of IkB kinase (IKK)-beta through activation of the cAMP-PKA pathway. Activation
      of Jun N-terminal kinase (JNK) pathway was also observed during GIP-induced
      inflammatory responses in adipocytes. The inhibition of JNK blocked GIP
      stimulated secretion of inflammatory cytokines and chemokines, as well as
      phosphorylation of IKKbeta. In addition, GIP-induced inflammatory response
      increased basal glucose uptake but inhibited insulin-stimulated glucose uptake.
      Moreover, GIP-induced adipocyte inflammation impaired insulin signaling in
      adipocytes as demonstrated by a reduction of AKT phosphorylation. Our results
      suggest that GIP might be one of the stimuli attributable to obesity-induced
      insulin resistance via the induction of adipocyte inflammation.

PMID- 22366644
TI  - Submarines, spacecraft and exhaled breath.
AB  - Foreword The International Association of Breath Research (IABR) meetings are an
      eclectic gathering of researchers in the medical, environmental and
      instrumentation fields; our focus is on human health as assessed by the
      measurement and interpretation of trace chemicals in human exhaled breath.  What
      may have escaped our notice is a complementary field of research that explores
      the creation and maintenance of artificial atmospheres practised by the submarine
      air monitoring and air purification (SAMAP) community.  SAMAP is comprised of
      manufacturers, researchers and medical professionals dealing with the engineering
      and instrumentation to support human life in submarines and spacecraft (including
      shuttlecraft and manned rockets, high-altitude aircraft, and the International
      Space Station (ISS)).  Here, the immediate concerns are short-term survival and
      long-term health in fairly confined environments where one cannot simply 'open
      the window' for fresh air.  As such, one of the main concerns is air monitoring
      and the main sources of contamination are CO(2) and other constituents of human
      exhaled breath.    Since the inaugural meeting in 1994 in Adelaide, Australia,
      SAMAP meetings have been held every two or three years alternating between the
      North American and European continents.  The meetings are organized by Dr Wally
      Mazurek (a member of IABR) of the Defense Systems Technology Organization (DSTO)
      of Australia, and individual meetings are co-hosted by the navies of the
      countries in which they are held.  An overriding focus at SAMAP is life support
      (oxygen availability and carbon dioxide removal).  Certainly, other air
      constituents are also important; for example, the closed environment of a
      submarine or the ISS can build up contaminants from consumer products, cooking,
      refrigeration, accidental fires, propulsion and atmosphere maintenance. However,
      the most immediate concern is sustaining human metabolism: removing exhaled CO(2)
      and replacing metabolized O(2). Another important concern is a suite of products
      from chemical reactions among oxidizing compounds with biological chemicals such
      as amines, thiols and carbonyls.  SAMAP Meeting  We (Armin and Joachim) attended
      the 2011 SAMAP conference in Taranto, Italy (10-14 October), which occurred just
      a few weeks after the IABR meeting in Parma, Italy (11-15 September 2011).  It
      was held at the Officers' Club of the Taranto Naval Base under the patronage of
      the Italian navy; the local host was Lucio Ricciardi of the University of
      Insubria, Varese, Italy.  At the 2011 SAMAP meeting, the theme was air
      independent propulsion (AIP), meaning the capability of recharging the main
      batteries of the submarine without the need to surface.  Only a few navies (e.g.
      US, UK, France, Russia, China) have historically had this capability using
      nuclear-powered submarines that can function underwater for extended periods of
      time (months). Most navies operate submarines with conventional diesel-electric
      propulsion, wherein diesel-powered generators charge battery banks which then
      drive an electric motor connected to the propeller. The batteries are charged
      while the boat is on the surface or during snorkelling, when the boat is
      submerged a few meters below the surface and a snorkel tube is extended to the
      surface. The period between battery charges can vary from several hours to one or
      two days depending on the power requirements and the nature of the mission. The
      process is necessary for breathing air revitalization (flushing out accumulated
      contaminants) and for the operation of the diesel engines. However, during this
      period the submarine is vulnerable to detection. Since the 1940s there have been
      various attempts to develop a power generation system that is independent of
      external air (AIP). To this end hydrogen peroxide was initially used and later
      liquid oxygen (LOX). Currently, most AIP submarines use fuel cell technology (LOX
      and hydrogen) to supplement the conventional diesel-electric system in order to
      extend the underwater endurance to 2-3 weeks. These propulsion engineering
      changes also reduce periodic ventilation of the submarine's interior and thus put
      a greater burden on the various maintenance systems.  We note that the
      spaceflight community has similar issues; their energy production mechanisms are
      essentially air independent in that they rely almost entirely on photovoltaic
      arrays for electricity generation, with only emergency back-up power from alcohol
      fuel cells.   In response to prolonged underwater submarine AIP operations,
      months-long spaceflight operations onboard the ISS and planning for future years
      long missions to Mars, there has been an increasing awareness that bio-monitoring
      is an important factor for assessing the health and awareness states of the
      crewmembers.  SAMAP researchers have been proposing various air and bio
      monitoring instruments and methods in response to these needs.  One of the most
      promising new methodologies is the non-invasive monitoring of exhaled breath. 
      So, what do the IABR and SAMAP communities have in common?   Inhalation
      toxicology. We are both concerned with contamination from the environment, either
      as a direct health threat or as a confounder for diagnostic assessments. For
      example, the exhaled breath from subjects in a contaminated and enclosed
      artificial environment (submarine or spacecraft) can serve as a model system and
      a source of contamination for their peers in a cleaner environment. In a similar
      way, exhaled anaesthetics can serve as a source of contamination in
      hospital/clinical settings, or exhalation of occupational exposures to
      tetrachloroethylene can impact family members at home.   Instrumentation
      development. Both communities have similar needs for better, more specific and
      more sensitive instruments.  Certainly, the analytical instruments to be used
      onboard submarines and spacecraft have severe restrictions on energy use,
      physical size and ease of operation.  The medical and clinical communities have
      similar long-term plans for their analytical tools,  in this case to take breath
      analysis away from the large complex instruments in the laboratory to the
      outpatient clinic and eventually to the home care market.  Similarly, for
      environmental and public health research, it is always desirable to have easily
      operated and deployable instruments that can be taken to the field, rather than
      bringing numerous subjects to a central laboratory.    Bio-monitoring. Although
      the SAMAP community is much more focused on air rather than breath measurement,
      this is changing because of the realization that longer deployment times (on
      submarines and spacecraft) will affect more than just acute health.  To monitor
      longer-term health outcomes, there is a great deal of commonality between our
      respective research communities.  Any instrument that monitors for contaminants
      in environmental air could certainly be adapted to breath analysis for assessing
      exposures and health state.  Instruments that simultaneously provide rapid
      response and high specificity to a broad range of analytes, such as those based
      on optical spectroscopy and mass spectrometry, are particularly valued.  The path
      forward  We found the SAMAP meeting to be a worthwhile experience, largely from
      the discovery that another high-tech community exists with similar needs as the
      IABR community.  Some collaboration could be fruitful for us; we suggest that the
      IABR community stay in contact with SAMAP in the future and attempt to attend
      each other's meetings if possible.  SAMAP meetings tend to run on a two year
      cycle and so the next one has not yet been announced.  We will let the IABR
      community know when the next meeting is scheduled, and will certainly make the
      SAMAP people aware of IABR meetings and the Journal of Breath Research.   This
      article has been subjected to EPA Agency review and approved for publication.
      Statements do not necessarily reflect official Agency policy.

PMID- 22366645
TI  - Acupuncture combined with curcumin attenuates carbon tetrachloride-induced
      hepatic fibrosis in rats.
AB  - BACKGROUND: Increasingly, studies demonstrate the effectiveness of acupuncture
      therapy against liver fibrosis. Curcumin is a natural product with antifibrotic
      effects, but has poor pharmacokinetic profiles. This study aimed to evaluate
      whether acupuncture combined with curcumin could more potently attenuate liver
      fibrosis in chemical intoxicated rats. METHODS: 60 Sprague-Dawley male rats were
      randomly divided into control, model, sham, acupuncture, curcumin and combination
      therapy groups. During the establishment of fibrosis using carbon tetrachloride
      (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by
      mouth were performed simultaneously. After treatment, pathological indexes and
      histology for hepatic injury and fibrogenesis were detected. The expression of
      extracellular matrix (ECM) components was also determined. RESULTS: Acupuncture
      combined with curcumin potently protected the liver from CCl(4)-induced injury
      and fibrogenesis, as indicated by reduced levels of serum aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, hyaluronic
      acid, laminin and procollagen III. Combined use also led to significant liver
      histological improvements. Furthermore, combined use effectively inhibited ECM
      expression such as alpha-smooth muscle actin, fibronectin and alpha1(1) collagen.
      CONCLUSIONS: Acupuncture treatment could significantly enhance the antifibrotic
      efficacy of curcumin on CCl(4)-induced hepatic fibrosis in rats in vivo,
      suggesting that a combination of acupuncture with curcumin may be exploited for
      the prevention of hepatic fibrosis.

PMID- 22366646
TI  - Face validity, construct validity and training benefits of a virtual reality TURP
      simulator.
AB  - OBJECTIVE: To assess face validity, construct validity and the training benefits
      of a virtual reality TURP simulator. METHOD: 11 novices (no TURP experience) and
      7 experts (>200 TURP's) completed a virtual reality median lobe prostate
      resection task on the TURPsimTM (Simbionix USA Corp., Cleveland, OH). Performance
      indicators (percentage of prostate resected (PR), percentage of capsular
      resection (CR) and time diathermy loop active without tissue contact (TAWC) were
      recorded via the TURPsimTM and compared between novices and experts to assess
      construct validity. Verbal comments provided by experts following task completion
      were used to assess face validity. Repeated attempts of the task by the novices
      were analysed to assess the training benefits of the TURPsimTM. RESULTS: Experts
      resected a significantly greater percentage of prostate per minute (p < 0.01) and
      had significantly less active diathermy time without tissue contact (p < 0.01)
      than novices. After practice, novices were able to perform the simulation more
      effectively, with significant improvement in all measured parameters. Improvement
      in performance was noted in novices following repetitive training, as evidenced
      by improved TAWC scores that were not significantly different from the expert
      group (p = 0.18). CONCLUSIONS: This study has established face and construct
      validity for the TURPsimTM. The potential benefit in using this tool to train
      novices has also been demonstrated.

PMID- 22366647
TI  - Retinal neural progenitors express topographic map markers.
AB  - Transplantation of neural stem cells for replacing neurons after
      neurodegeneration requires that the transplanted stem cells accurately
      reestablish the lost neural circuits in order to restore function. Retinal
      ganglion cell axons project to visual centers of the brain forming circuits in
      precise topographic order. In chick, dorsal retinal neurons project to ventral
      optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior
      tectum and posterior neurons to anterior tectum; forming a continuous point-to
      point map of retinal cell position in the tectal projection. We found that when
      stem cells derived from ventral retina were implanted in dorsal host retina, the
      stem cells that became ganglion cells projected to dorsal tectum, appropriate for
      their site of origin in retina but not appropriate for their site of implant in
      retina. This led us to ask if retinal progenitors exhibit topographic markers of
      cell position in retina. Indeed, retinal neural progenitors express topographic
      markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and,
      conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal
      stem cells. The fact that neural progenitors express topographic markers has
      pertinent implications in using neural stem cells in cell replacement therapy for
      replacing projecting neurons that express topographic order, e.g., analogous
      neurons of the visual, auditory, somatosensory and motor systems.

PMID- 22366648
TI  - Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+
      metabolites and single nucleotide polymorphisms of CD38.
AB  - Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl
      cyclase activity, plays a critical role in mouse social behavior by regulating
      the release of oxytocin (OXT), which is essential for mutual recognition. When
      CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism
      spectrum disorders (ASDs), characterized by defects in reciprocal social
      interaction and communication, occur either sporadically or in a familial
      pattern. However, the etiology of ASDs remains largely unknown. Therefore, the
      theoretical basis for pharmacological treatments has not been established. Hence,
      there is a rationale for investigating single nucleotide polymorphisms (SNPs) in
      the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP
      rs3796863 (C>A) was associated with high-functioning autism (HFA) in American
      samples from the Autism Gene Resource Exchange. Although this finding was
      partially confirmed in low-functioning autism subjects in Israel, it has not been
      replicated in Japanese HFA subjects. The second SNP of interest, rs1800561
      (4693C>T), leads to the substitution of an arginine (R) at codon 140 by
      tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD
      and in family members of three pedigrees with variable levels of ASD or ASD
      traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower
      than those in ASD subjects lacking this allele. The OXT levels were unchanged in
      healthy subjects with or without this mutation. One proband with the R140W allele
      receiving intranasal OXT for approximately 3years showed improvement in areas of
      social approach, eye contact and communication behaviors, emotion, irritability,
      and aggression. Five other ASD subjects with mental deficits received nasal OXT
      for various periods; three subjects showed improved symptoms, while two showed
      little or no effect. These results suggest that SNPs in CD38 may be possible risk
      factors for ASD by abrogating OXT function and that some ASD subjects can be
      treated with OXT in preliminary clinical trials.

PMID- 22366649
TI  - Amyloid precursor protein accumulates in aggresomes in response to proteasome
      inhibitor.
AB  - Aggresomes are cytoplasmic inclusions which are localized at the microtubule
      organizing center (MTOC) as a result of induced proteasome inhibition, stress or
      over-expression of certain proteins. Aggresomes are linked to the pathogenesis of
      many neurodegenerative diseases. Here we studied whether amyloid precursor
      protein (APP), a type-I transmembrane glycoprotein, is localized in aggresomes
      after exposure to stress condition. Using confocal microscopy we found that APP
      is located in aggresomes and co-localized with vimentin, gamma-tubulin, 20S and
      ubiquitin at the MTOC in response to proteasome dysfunction. An interaction
      between vimentin and APP was found after proteasome inhibition suggesting that
      APP is an additional protein constituent of aggresomes. Suppression of the
      proteasome system in APP-HEK293 cells overexpressing APP or transfected with APP
      Swedish mutation caused an accumulation of stable, detergent-insoluble forms of
      APP containing poly-ubiquitinated proteins. In addition, brain homogenates from
      transgenic mice expressing human APP with the Arctic mutation demonstrated an
      interaction between APP and the aggresomal-marker vimentin. These data suggest
      that malfunctioning of the proteasome system caused by mutation or overexpression
      of pathological or non-pathological proteins may lead to the accumulation of
      stable aggresomes, perhaps contributing to the neurodegeneration.

PMID- 22366650
TI  - NR2A and NR2B subunits differentially mediate MAP kinase signaling and
      mitochondrial morphology following excitotoxic insult.
AB  - NMDA receptors are essential for neurotransmission and key mediators of synaptic
      signaling, but they can also trigger deleterious degenerative processes that lead
      to cell death. Growing evidence suggests that selective blockade of the
      heterogeneous subunits that comprise the NMDA receptor may enable better control
      of pharmacotherapies for treating neurological diseases and injuries. We
      investigated the relationship between NMDAR activation, MAPK signaling, and
      mitochondrial shape following an excitotoxic insult. NR2A- and NR2B-containing
      NMDARs differentially mediated acute changes in cytosolic calcium, alterations in
      mitochondrial morphology, and phosphorylation of the MAPKs ERK and JNK.
      Activation of NR2A-containing NMDARs was associated with JNK phosphorylation that
      was neuroprotective in neuronal cultures subjected to excitotoxicity. In
      contrast, activation of NR2B-containing NMDARs triggered calcium accumulation in
      mitochondria that was strongly associated with mitochondrial swelling and
      neuronal cell death. Indeed, while blockade of NR2B-containing receptors was
      neuroprotective, this protection was lost when NR2A-initiated JNK phosphorylation
      was inhibited. Given the modest selectivity of the NR2A inhibitor, NVP-AAM077,
      the results highlight the significance of the relative, rather than absolute,
      activation of these two NMDA subtypes in modulating cell death pathways.
      Therefore, the balance between concurrent activation of NR2B-containing and NR2A
      containing NMDARs dictates neuronal fate following excitotoxicity.

PMID- 22366651
TI  - Ect2, an ortholog of Drosophila Pebble, regulates formation of growth cones in
      primary cortical neurons.
AB  - In collaboration with Marshall Nirenberg, we performed in vivo RNA interference
      (RNAi) genome-wide screening in Drosophila embryos. Pebble has been shown to be
      involved in Drosophila neuronal development. We have also reported that depletion
      of Ect2, a mammalian ortholog of Pebble, induces differentiation in NG108-15
      neuronal cells. However, the precise role of Ect2 in neuronal development has yet
      to be studied. Here, we confirmed in PC12 pheochromocytoma cells that inhibition
      of Ect2 expression by RNAi stimulated neurite outgrowth, and in the mouse
      embryonic cortex that Ect2 was accumulated throughout the ventricular and
      subventricular zones with neuronal progenitor cells. Next, the effects of Ect2
      depletion were studied in primary cultures of mouse embryonic cortical neurons:
      Loss of Ect2 did not affect the differentiation stages of neuritogenesis, the
      number of neurites, or axon length, while the numbers of growth cones and growth
      cone-like structures were increased. Taken together, our results suggest that
      Ect2 contributes to neuronal morphological differentiation through regulation of
      growth cone dynamics.

PMID- 22366652
TI  - Tehranolide inhibits proliferation of MCF-7 human breast cancer cells by inducing
      G0/G1 arrest and apoptosis.
AB  - Tehranolide, a novel natural sesquiterpene lactone with an endoperoxide group,
      bears a structural similarity to artemisinin and has been shown to inhibit cell
      growth. However, the underlying mechanisms of these activities remain obscure.
      The purpose of this study was to investigate the fundamental mechanisms by which
      tehranolide inhibits growth in MCF-7 cells. Cell growth was determined by using
      the MTT viability assay and counting cells. Apoptosis and cell-cycle progression
      were evaluated by means of Hoechst 33258 staining, flow cytometry with annexin
      V/propidium iodide double staining, and ROS formation. The protein expression of
      Bax and Bcl-2 was demonstrated by Western blotting. Moreover, to determine the
      molecular mechanism whereby tehranolide mediates G0/G1 arrest, the expression of
      PI3K, p-PI3K, Akt, p-Akt, p27kip1, cyclin D1, and CDK4 was monitored. Cell
      proliferation was significantly inhibited by tehranolide in a dose- and time
      dependent manner. This compound inhibited cell proliferation and induced G0/G1
      arrest through the PI3K/Akt/cyclin D1 pathway. It also induced apoptosis and an
      increase in ROS. In addition, an increase in cytochrome c and Bax, as well as a
      decrease in Bcl-2, was observed. Moreover, blocking the CD95 receptor with an
      anti-CD95 antibody (ZB4) had no effect on tehranolide-mediated apoptosis. This
      study has yielded promising results, which show for the first time that
      tehranolide does inhibit the growth of cancer cells. The selective inhibition of
      cancer cell growth, the apoptosis induction via the mitochondrial pathway, and
      the G0/G1 arrest by modulating the PI3K/AKT signaling pathway and downregulating
      cyclin D1, which leads to the release of p27kip1 and the association of this
      inhibitor with the cyclin E/CDK2 complex, ultimately preventing cell-cycle
      progression from G1 to S phase, all serve to provide support for further studies
      of tehranolide as a possible anticancer drug in the clinical treatment of cancer.

PMID- 22366653
TI  - Discovery of GS-9451: an acid inhibitor of the hepatitis C virus NS3/4A protease.
AB  - The discovery of GS-9451 is reported. Modification of the P3 cap and P2 quinoline
      with a series of solubilizing groups led to the identification of potent HCV NS3
      protease inhibitors with greatly improved pharmacokinetic properties in rats,
      dogs and monkeys.

PMID- 22366654
TI  - 2-Amidino analogs of glycine-amiloride conjugates: inhibitors of urokinase-type
      plasminogen activator.
AB  - The relative non-toxicity of the diuretic amiloride, coupled with its selective
      inhibition of the protease urokinase plasminogen activator (uPA), makes this
      compound class attractive for structure-activity studies. Herein we substituted
      the C(2)-acylguanidine of C(5)-glycyl-amiloride with amidine and amidoxime
      groups. The data show the importance of maintaining C(5)-hydrophobicity. The C(5)
      benzylglycine analogs containing either C(2)-acylguanidine or amidine inhibited
      uPA with an IC(50) ranging from 3 to 7 MUM and were cytotoxic to human U87
      malignant glioma cells.

PMID- 22366655
TI  - Anti-proliferative effects of the novel ceramide analog (S)-2-(benzylideneamino)
      3-hydroxy-N-tetrade-cylpropanamide in chemoresistant cancer.
AB  - The ceramide-sphingosine-1-phosphate rheostat is a promising therapeutic target.
      Here, the novel ceramide analog (S)-2-(benzylideneamino)-3-hydroxy-N-tetrade
      cylpropanamide is shown to block proliferation and enhance the efficacy of the
      clinical chemotherapeutics, etoposide and doxorubicin. These results demonstrate
      the therapeutic potential of this compound in treating both endocrine resistant
      and chemoresistant breast cancer.

PMID- 22366656
TI  - Oroxylin A analogs exhibited strong inhibitory activities against iNOS-mediated
      nitric oxide (NO) production.
AB  - A number of oroxylin A analogs were prepared and evaluated for their inhibitory
      activities against iNOS-mediated nitric oxide (NO) production from LPS-stimulated
      BV2 cells. The analogs were synthesized from purchased 2'-hydroxy-4,5,6
      trimethoxyacetophenone and aldehydes in 3 steps. Among the tested compounds,
      several analogs (3b, 3c, 3d, 3f) exhibited strong inhibitory activities.
      Especially, the analog with 4-nitrophenyl group (3b) showed stronger inhibitory
      activity (IC(50)=4.73 MUM) than that of wogonin (IC(50)=7.80 MUM).

PMID- 22366657
TI  - A novel series of benzimidazole NR2B-selective NMDA receptor antagonists.
AB  - A series of novel benzimidazoles are discussed as NR2B-selective N-methyl-d
      aspartate (NMDA) receptor antagonists. High throughput screening (HTS) efforts
      identified a number of potent and selective NR2B antagonists such as 1.
      Exploration of the substituents around the core of this template identified a
      number of compounds with high potency for NR2B (pIC(50) >7) and good selectivity
      against the NR2A subunit (pIC(50) <4.3) as defined by FLIPR-Ca(2+) and
      radioligand binding studies. These agents offer potential for the development of
      therapeutics for a range of nervous system disorders including chronic pain,
      neurodegeneration, migraine and major depression.

PMID- 22366658
TI  - Penicillin inhibitors of purple acid phosphatase.
AB  - Purple acid phosphatases (PAPs) are binuclear metallohydrolases that have a
      multitude of biological functions and are found in fungi, bacteria, plants and
      animals. In mammals, PAP activity is linked with bone resorption and over
      expression can lead to bone disorders such as osteoporosis. PAP is therefore an
      attractive target for the development of drugs to treat this disease. A series of
      penicillin conjugates, in which 6-aminopenicillanic acid was acylated with
      aromatic acid chlorides, has been prepared and assayed against pig PAP. The
      binding mode of most of these conjugates is purely competitive, and some members
      of this class have potencies comparable to the best PAP inhibitors yet reported.
      The structurally related penicillin G was shown to be neither an inhibitor nor a
      substrate for pig PAP. Molecular modelling has been used to examine the binding
      modes of these compounds in the active site of the enzyme and to rationalise
      their activities.

PMID- 22366659
TI  - Enhancement of rostral ventrolateral medulla neuronal nitric-oxide synthase
      nitric-oxide signaling mediates the central cannabinoid receptor 1-evoked pressor
      response in conscious rats.
AB  - Our recent studies implicated brainstem GABAergic signaling in the central
      cannabinoid receptor 1 (CB(1)R)-mediated pressor response in conscious rats.
      Given the well established link between neuronal nitric-oxide synthase
      (nNOS)/nitric oxide (NO) signaling and GABAergic transmission in brainstem
      cardiovascular regulating areas, we elucidated the role of nNOS-generated NO in
      the central CB(1)R-elicited pressor response. Compared with vehicle,
      intracisternal (i.c.) microinjection of the CB(1)R agonist (R)-(+)-[2,3-dihydro-5
      methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl) methanone mesylate (WIN55212-2) (15 MUg/rat) significantly enhanced
      nNOS phosphorylation as well as the total nitrate and nitrite content in the
      rostral ventrolateral medulla (RVLM) at 5, 10, and 30 min, which paralleled the
      elicited pressor response. These findings were corroborated by: 1) the parallel
      dose-related increases in blood pressure and RVLM-NO levels, measured in real
      time by in vivo electrochemistry, elicited by intra-RVLM WIN55212-2 (100, 200, or
      300 pmol /80 nl; n = 5) in conscious rats; and 2) the significantly higher
      phosphorylated nNOS (p-nNOS) levels in the WIN55212-2-injected RVLM compared with
      the contralateral RVLM. Subsequent neurochemical studies showed that WIN55212-2
      (15 MUg/rat i.c.) significantly increased the number and percentage of neurons
      immunostained for nNOS (nitroxidergic neurons) and c-Fos (marker of neuronal
      activity) within the RVLM. The increases in blood pressure and the neurochemical
      responses elicited by intracisternal WIN55212-2 were attenuated by prior central
      CB(1)R blockade by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-1H-pyrazole-3-carboxamide (AM251; 30 MUg/rat i.c.) or selective nNOS
      inhibition by N(omega)-propyl-(L)-arginine (1 MUg/rat i.c.). These findings
      implicate RVLM p-nNOS/NO signaling as a molecular mechanism in the central CB(1)R
      evoked pressor effect in conscious rats.

PMID- 22366660
TI  - Smooth muscle pharmacology in the isolated virgin and pregnant rat uterus and
      cervix.
AB  - Uterine smooth muscle function is established, but comparatively little is known
      about cervical smooth muscle pharmacology. We performed a proof-of-principle
      experiment that smooth muscle was expressed in the cervix in both virgin and
      pregnant rats, using the uterus as a comparator. We tested whether all tissues
      were pharmacologically responsive to contractile and relaxant agonists.
      Immunohistochemistry revealed the expression of smooth muscle alpha-actin in all
      tissues. The isolated tissue bath was used to measure isometric contractility of
      uterine strips and whole cervices from virgin and pregnant (day 11 +/- 2) female
      Sprague-Dawley rats. We tested classic activators of uterine smooth muscle
      contraction and relaxation in both uterus and cervix. All tissues contracted to
      the depolarizing agent potassium chloride, prostaglandin F2alpha, muscarinic
      cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N
      trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues,
      the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was
      present. Both cervix and uterus (virgin and pregnant) had concentration
      dependent, near-complete relaxation to the adrenergic agonist norepinephrine and
      adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b
      trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5
      yl acetate]. The beta-adrenergic receptor agonist isoproterenol was less potent
      in pregnant cervix versus virgin by ~10-fold. All tissues, particularly the
      cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing
      ~20% maximally. These findings support the importance of smooth muscle in the
      cervix, the use of the isolated cervix in pharmacological studies, and a
      similarity between smooth muscle pharmacology of the nonpregnant uterus and
      cervix. This work highlights the unappreciated smooth muscle function of the
      cervix versus uterus and cervical changes in pharmacology during pregnancy.

PMID- 22366662
TI  - Health economics and outcomes research within drug development: challenges and
      opportunities for reimbursement and market access within biopharma research.
AB  - Healthcare decision makers who determine funding for new medical technologies
      depend on manufacturers to provide evidence of the technology's efficacy, safety
      and cost-effectiveness. Constrained budgets and increasing reliance on formal
      health technology assessment (HTA) have created an abundance of external hurdles
      that manufacturers must navigate to ensure successful product commercialization.
      These demands have pushed pharmaceutical companies to adjust their internal
      structures to coordinate generation of appropriate evidence. In this article we
      summarize internal and external opportunities for manufacturers to establish a
      foundation of evidence for successful market access, starting in Phase I of
      development and continuing throughout the post-approval product lifecycle.

PMID- 22366663
TI  - Histopathological survey of pathogens and commensals of white-clawed crayfish
      (Austropotamobius pallipes) in England and Wales.
AB  - A histopathological survey of white-clawed crayfish (Austropotamobius pallipes)
      from six rivers in England and Wales was conducted between November 2007 and
      September 2011. A. pallipes bacilliform virus (ApBV) was present in four samples;
      infected crayfish showed pathological responses ranging from mild hypertrophy of
      infected nuclei and emargination of chromatin through to loss of architecture of
      the hepatopancreatic cells. Crayfish were found to be hosts to two different
      ciliate species, mites, nematodes, digeneans and the microsporidian Thelohania
      contejeani. The variation in disease presence between populations highlights the
      importance of conducting appropriate surveys of native crayfish prior to movement
      of animals to refugia sites for relocation, restocking or breeding programmes.

PMID- 22366661
TI  - Cognitive, academic, and behavioral correlates of medication adherence in
      children and adolescents with perinatally acquired HIV infection.
AB  - OBJECTIVE: Medication adherence is critical to the success of antiretroviral
      therapies for children and youth with perinatally acquired HIV. Factors that
      influence successful transition of medication responsibility from caregivers to
      youth are poorly understood. The purpose of this study was to evaluate the
      relationship of medication adherence with demographic, cognitive, academic, and
      behavioral characteristics. METHODS: Randomly selected youth, N = 151, aged 8 to
      18 years, completed cognitive and academic measures, and they and their
      caregivers completed questionnaires assessing behavior and emotional well-being.
      An announced pill count and questionnaires completed by youth and their
      caregivers were used to evaluate adherence. RESULTS: Of 151 participants, 100
      completed all adherence measures. Adherence rates varied by assessment method.
      Nonadherence (<90%) by pill count was associated with older child age, greater
      youth responsibility for medications, and other demographic and medication
      regimen variables. Verbal impairment predicted better self-reported adherence and
      reading problems predicted better self- and caregiver-reported adherence. Youth
      reported locus of control was associated with pill count nonadherence, and poor
      relationships with parents were associated with youth-reported nonadherence.
      CONCLUSIONS: Consideration of youth cognitive or academic status may be helpful
      in evaluating medication adherence in patients with perinatally acquired HIV
      infection, particularly when using self- or caregiver reports to assess
      adherence. Vigilance for adherence problems is indicated when youth are older,
      responsible for medications, report poor caregiver relationships, and/or sense a
      lack of control over their lives.

PMID- 22366664
TI  - Effects of salinity on hard clam (Mercenaria mercenaria) defense parameters and
      QPX disease dynamics.
AB  - QPX (Quahog Parasite Unknown) is a protistan parasite affecting hard clams
      (Mercenaria mercenaria) along the Northeast coast of the United States. The fact
      that QPX disease epizootics are usually observed in field sites with high
      salinities led to the general assumption that salinity represents an important
      factor for disease distribution. This study was designed to investigate the
      effect of salinity on QPX disease development as well as constitutive and QPX
      induced defense factors in M. mercenaria. Naive and QPX-infected (both
      experimentally and naturally) clams were submitted to 17 and 30 psu for 4 months.
      Standard and QPX-specific cellular and humoral defense parameters were assessed
      after 2 and 4 months. These included total and differential hemocyte counts,
      reactive oxygen species production, phagocytic activity of hemocytes, lysozyme
      concentration in plasma, anti-QPX activity in plasma and resistance of hemocytes
      to cytotoxic QPX extracellular products. Results demonstrated higher QPX
      associated mortality in naturally infected clams maintained at high salinity
      compared to those held at 17 psu. Our findings also showed an increase in
      mortality following experimental challenge with QPX in clams submitted to 30 psu
      but not in those held at 17 psu. Constitutive clam defense factors and the
      response to QPX challenge were also affected by salinity. QPX challenge caused
      significant but transitory changes in hemolymph parameters that were obvious at 2
      months but disappeared at 4 months. Overall, our results show that salinity
      modulates clam immunity and the progress of QPX disease although its impact
      appears secondary as compared to findings we reported earlier for temperature.

PMID- 22366665
TI  - Metastatic adenoid cystic carcinoma of the eyelid.
AB  - A 48-year-old man presented with an enlarging mass of the right upper eyelid over
      a 1-month period. Nine years prior, the patient was diagnosed with adenoid cystic
      carcinoma (ACC) of the right maxillary sinus and underwent a total maxillectomy
      followed by local radiotherapy. Over the previous year, the patient had been
      treated with chemotherapy and radiotherapy for multiple organ metastases,
      including the spine, chest, and oral cavity. Ophthalmic examination revealed a
      white, round mass on the tarsal conjunctiva of the right upper eyelid, measuring
      approximately 1 * 1 cm, and 2 palpable subcutaneous masses near the inferior
      orbital rim. Excisional biopsies of the masses were performed, and the
      histopathological findings were consistent with ACC with solid and cribriform
      patterns. Herein, the authors describe a case of metastatic ACC of the eyelid,
      which has not been described in the literature to their knowledge.

PMID- 22366666
TI  - Percutaneous drainage and ablation as first line therapy for macrocystic and
      microcystic orbital lymphatic malformations.
AB  - PURPOSE: To review the management of orbital lymphangiomas and to propose a new
      treatment for both macrocystic and microcystic lymphatic malformations of the
      orbit. METHODS: A retrospective case series of all patients from the authors'
      practice from 2001 to the present who met the histopathologic and/or diagnostic
      imaging criteria for orbital lymphatic malformation was reviewed. Lymphatic
      malformation was diagnosed if there was a multilobulated pattern on CT or a
      cystic internal structure on ultrasonography. In patients that were treated,
      macrocysts (>1 cm) were treated with dual-drug chemoablation (sequential
      intracystic sodium tetradecyl sulfate and ethanol); doxycycline injections were
      used for microcysts. The goal of treatment was complete cyst ablation documented
      by ultrasonography or MRI. RESULTS: Twenty patients met the inclusion criteria.
      They were separated in 3 groups based on the anatomical location of the lymphatic
      malformation: deep, superficial, or combined. Deep orbital lymphatic malformation
      presented in 14 patients (70%), superficial presented in 4 patients (20%), and
      both deep and superficial presented in 2 patients (10%). Thirteen of the 20
      patients underwent percutaneous sclerotherapy. Of those treated, 7 patients
      (53.8%) had lymphatic malformations (LM), while 6 patients (46.2%) had venous
      lymphatic malformations (VLMs). The average number of treatments required to
      achieve complete cyst ablation in patients with LM was 1.7. The average number of
      treatments required for patients with VLM was 3.0; however, some of these
      patients continue to have the venous component of their lesions treated.
      Clinically, all treated patients maintained or improved an average of one Snellen
      line (-0.16 decimal Snellen equivalent) from their preoperative visual acuity to
      their last recorded follow-up visit. There was a mean reduction in proptosis of
      2.4 mm (p - 0.003, confidence interval [CI] 0.838 to 3.962), which was
      statistically significant. There were no recurrences (0%) in patients who
      completed treatment with cyst ablation (n - 8) at an average follow-up period of
      43 months (range 6-96, standard deviation 30). There were no data available as to
      the recurrence status of one patient. Four patients were still undergoing
      treatment for a venous component at the time of this review. CONCLUSIONS:
      Percutaneous sclerotherapy provides a safe and effective treatment for both
      macrocystic and microcystic orbital lymphatic malformations as a primary
      treatment or for recurrence after surgical intervention.

PMID- 22366667
TI  - Occurrence and surgical management of a cerebrospinal fluid-filled cystoid space
      following routine enucleation.
AB  - A 73-year-old woman underwent routine enucleation for a blind, painful eye
      related to end-stage diabetic retinopathy and neovascular glaucoma. A large
      cystoid space, in continuity with the optic nerve stump, formed around the
      implant in the first few weeks following surgery. Aspirated contents were
      positive for beta-2 transferrin, confirming cerebrospinal fluid origin. Multiple
      comorbidities delayed surgical intervention, but the condition was ultimately
      managed with exposure of the patent optic nerve sheath at the compartment's base,
      temporary control of cerebrospinal fluid leakage with pulmonary hyperventilation
      and topical fibrin glue, dissection and vascular-clip ligation of the nerve
      stump, and capping with a dermis-fat graft. To the authors' knowledge, this
      postenucleation entity has not been previously described, and asymptomatic
      idiopathic intracranial hypertension may have been an underlying factor.

PMID- 22366668
TI  - Bilateral diffuse orbital myositis in a patient with relapsing ulcerative
      colitis.
AB  - Ophthalmic manifestations of inflammatory bowel disease are common, but orbital
      inflammatory disease is rare with most cases associated with Crohn disease. We
      describe the first case of bilateral, diffuse, orbital myositis associated with
      ulcerative colitis in a patient taking infliximab. Within 72 hours of intravenous
      methylprednisolone treatment, the orbital inflammation dramatically improved.
      After 8 weeks of prednisone, it completely resolved and has remained quiet for 13
      months. This is only the third report of ulcerative colitis-associated orbital
      inflammatory disease.

PMID- 22366669
TI  - Desmoplastic trichoepithelioma:  report of a unique periocular case.
AB  - In a 58-year-old woman with blepharospasm, a slowly enlarging left inferomedial
      eyelid lesion developed. It measured 3 * 5 mm and was nonulcerated, well
      circumscribed, whitish, upraised, and firm. An initial incomplete excision
      followed by a total repeated excision revealed small squamous microcysts, often
      exhibiting calcifications and cords of nonclefting basaloid cells embedded in a
      scirrhous stroma characteristic of desmoplastic trichoepithelioma (DTE).
      Immunohistochemical investigations disclosed CD34-positive stromal fibroblasts
      and many CK20-positive Merkel cells located among the epithelial cells, features
      absent in mimicking sclerosing basal cell carcinoma (BCC). The tumor has not
      recurred during 6 months of follow up. Besides BCC, the differential diagnosis
      chiefly concerns syringoma and microcystic adnexal carcinoma. Surgical therapy
      should aim at complete excision but does not have to be as extensive or
      aggressive as that used for morpheic or sclerosing BCC because of its lack of
      diffusely infiltrating margins.

PMID- 22366670
TI  - Loop-mediated isothermal amplification (LAMP) for malarial parasites of humans:
      would it come to clinical reality as a point-of-care test?
AB  - Loop-mediated isothermal amplification (LAMP) is a novel molecular method that
      accelerates and facilitates DNA amplification and detection under isothermal
      conditions. It represents a revolution in molecular biology by reducing the high
      cost, turnaround time and technicality of polymerase chain reaction and other
      amplification methods. It has been applied for the diagnosis of a variety of
      viral, bacterial, parasitic and other diseases in the biomedical field. LAMP has
      been involved in studies concerning the diagnosis of malaria which is still a
      major cause of morbidity and mortality in different parts of the world. For the
      success attained with this technology to diagnose human malaria, is it time to
      think that LAMP-based point-of-care diagnostics come to application to support
      the diagnosis of clinical malaria cases? The present review deals with the use of
      LAMP in the diagnosis of malaria and related investigations to make a view on
      what has been investigated and highlights the future perspectives regarding the
      possible applications of LAMP in diagnosis of the disease.

PMID- 22366671
TI  - A cross-sectional sero-epidemiological study of canine leishmaniasis in Greek
      mainland.
AB  - Canine leishmaniasis is endemic in Greece as in other countries of the
      Mediterranean basin. In this study, the regional prevalence of canine
      seropositivity to Leishmania spp. in Greek mainland was simultaneously assessed
      in 7 different regions. A total of 2620 serum samples were collected from
      clinically healthy dogs and were tested for anti-L. infantum antibodies by
      indirect immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent
      assay (ELISA). A high degree of agreement (kappa=0.96) was observed between these
      two tests. The seroprevalence rate in the whole study population was nearly 20%,
      being highest among dogs living in Attiki (30.12%) and lowest for those living in
      Florina (2.05%). There was no difference in terms of the gender of the dogs,
      their length of hair coat or their utility; on the contrary, seroprevalence rates
      were significantly higher among dogs in the age groups of 1-3 years (23.39%) and
      3-9 years (23.35%) than in younger (2.26%) or older (6.03%) dogs. Epidemiological
      data on the seroprevalence of canine leishmaniasis provide indirect information
      on the prevalence of the infection and the disease and are necessary to implement
      and then to evaluate the effectiveness of control measures.

PMID- 22366672
TI  - Toxicogenomic analysis of the gene expression changes in rat liver after a 28-day
      oral Tripterygium wilfordii multiglycoside exposure.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii multiglycoside (GTW),
      which is an extract derived from Tripterygium wilfordii Hook.f., has been used
      for the treatment of rheumatoid arthritis and other immune diseases in China.
      However, its potential hepatotoxicity has not been completely investigated. THE
      AIM OF THE STUDY: The aim of the study was to determine the hepatotoxicity of GTW
      in Wistar rats and to investigate the underlying cellular mechanism further by
      microarray analysis. MATERIALS AND METHODS: Doses of GTW at 60, 100 and
      120mg/kg/day were administered by oral gavage for subchronic toxicity in Wistar
      rats. Changes in the hepatic gene expression were identified with oligonucleotide
      microarrays at the 100-mg/kg/day dose level to study the hepatotoxic mechanism of
      GTW. RESULTS AND CONCLUSIONS: A number of changes in the body weight and food
      consumption, absolute and relative liver weight, biochemical analysis and
      histopathology were observed after the subacute exposure to GTW, and a dose
      dependent hepatotoxicity was observed. A total of 1312 genes were found to be
      significantly altered (2-fold, P<0.05), including 582 up-regulated genes and 730
      down-regulated genes. According to our biological pathway analysis, the GTW
      resulted in aberrant gene expression in metabolic pathways and the peroxisome
      proliferator-activated receptor (PPAR) signaling pathway and cellular stress.
      Real-time PCR analyses of several genes verified these results. Consequently, our
      gene expression microarray study will be useful for future GTW hepatotoxicity
      studies.

PMID- 22366673
TI  - Effects of taraxasterol on inflammatory responses in lipopolysaccharide-induced
      RAW 264.7 macrophages.
AB  - AIM OF THE STUDY: Taraxasterol, a pentacyclic-triterpene, was isolated from the
      Chinese medicinal herb Taraxacum officinale. In the present study, we
      investigated the in vitro anti-inflammatory activity of taraxasterol in
      lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. MATERIALS AND
      METHODS: RAW 264.7 cells were pretreated with 2.5, 5, or 12.5MUg/ml of
      taraxasterol 1h prior to treatment with 1MUg/ml of LPS. Nitric oxide (NO) level
      in supernatants from cells was examined by Griess reaction, the concentrations of
      prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6) were measured by ELISA. Nuclear factor
      kappa B (NF-kappaB) activation was evaluated by immunocytochemical analysis.
      RESULTS: We found that taraxasterol inhibited NO, PGE(2), TNF-alpha, IL-1beta and
      IL-6 production in LPS-induced RAW 264.7 macrophages in a dose-dependent manner.
      Further studies revealed that taraxasterol prevented the LPS-induced NF-kappaB
      translocation from cytoplasm into nuclear. CONCLUSIONS: These results indicate
      that taraxasterol has anti-inflammatory effect by blocking NF-kappaB pathway.

PMID- 22366674
TI  - Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker
      ethanol extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eupolyphaga sinensis Walker popularly known as
      "preferred drug to regulate blood flow" are traditionally used in folk medicine
      in the treatment of ecchymoma, posttraumatic wound, hepatic fibrosis and tumor.
      AIM OF THE STUDY: To characterize chemical compositions and to evaluate the
      antitumor and immunomodulatory of Eupolyphaga sinensis Walker ethanol extract
      (ESEE) in hepatocarcinoma H(22) bearing mice. MATERIALS AND METHODS: ESEE was
      obtained by ethanol reflux extraction and analyzed by gas chromatography-mass
      spectrometry (GC-MS) after methylation. ICR mice were treated with ESEE for 14
      consecutive days at doses of 31mg/kg (low-dose), 62mg/kg (mid-dose) and 124mg/kg
      (high-dose) after H(22) tumor cells were implanted. At the end of the
      experiments, the tumor weight of each mouse was measured. Levels of serum TNF
      alpha and IFN-gamma was assayed by ELISA. Protein expressions of Bax, Bcl-2 and
      caspases-3 were detected by immunohistochemistry. RESULTS: Chemical analysis
      revealed the presence of 6 components that account for 97.55% of fatty acids,
      indicating the occurrence of saturated and polyunsaturated fatty acids. Oral
      administration of ESEE could inhibit tumor growth, promote Th1 type cytokine
      productions (TNF-alpha and IFN-gamma) and induce apoptosis of hepatocarcinoma via
      increase of Bax/Bcl-2 ratio and activation of caspases-3. Oral administration of
      ESEE in a dosage of 6.2g/kg did not lead to toxic effects in mice. CONCLUSIONS:
      ESEE was effective in inhibiting tumor growth in vivo and could also serve as
      immunoadjuvant for tumor therapy.

PMID- 22366675
TI  - Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va
      Boyer Ahmad province of Iran.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are an important element of
      medical system. These resources are usually regarded as part of cultural
      traditional knowledge. We present for the first time the results of an
      ethnobotanical survey in Kohghiluyeh va Boyer Ahmad province of Iran, conducted
      between 2008 and 2010. This information could be the basis of an evidence based
      investigation to discover new drugs. MATERIALS AND METHODS: Ethnobotanical data
      were analyzed by use-reports in addition important indices like relative
      frequency of citation (RFC) and cultural importance index (CI) were calculated.
      Totally 23 informants were interviewed. RESULTS: Our study reports 138
      traditionally used plant species, belonging to 52 plant families from this
      province. Asteraceae and Lamiaceae are the dominant locally used families. The
      highest number of species and application were reported for digestive system
      disorder, metabolic disorder and respiratory system, respectively. The part of
      the plant most frequently used was the aerial part (31.9%), leaves (14.8%) and
      fruits (11.7%). The plants are used both for medicinal and non-medicinal
      purposes. Daphne mucronata Royle. and Teucrium polium L. have the largest value
      of relative frequency of citation and cultural importance index, respectively.
      CONCLUSION: Kohghiluyeh va Boyer Ahmad has good ethnobotanical potential for
      medicinal plants. This study is the first contribution to the ethnobotany of this
      region. We have gathered from this province some considerable knowledge about
      local medicinal plants for treating common health problem that is ready to be
      further investigated in the laboratory.

PMID- 22366676
TI  - Saponin rich fractions from Polygonatum odoratum (Mill.) Druce with more
      potential hypoglycemic effects.
AB  - AIMS: The root of Polygonatum odoratum (YuZhu), also a medicinal food has long
      been used for the treatment of diabetes. The objective of the study was to
      characterize the anti-diabetic active fractions or compounds in this herb.
      MATERIALS AND METHODS: Fractions with a different polarity were prepared by
      solvent extraction and macroporous absorptive resin (D101) column and their anti
      diabetic potentials were evaluated by glucose uptake in HepG2 cells and STZ
      induced diabetic rats. In addition, alpha-glycosidase inhibitory activities of
      active fractions were measured in vitro and chemical compositions including
      saponin, total flavonoids and total sugar in the fractions were determined.
      RESULTS: The n-buthanol fraction, a saponin-rich fraction obtained by
      partitioning the ethanol extract with n-buthanol after petroleum ether and acetic
      ether showed the highest anti-diabetic potential in glucose uptake in HepG2 cells
      followed by acetic ether fraction which was rich in flavonoids. Further
      fractionation the saponin-rich fraction using macroporous resin column (D101),
      polysaccharide, flavonoid and saponin rich fractions were obtained by elution
      with water, 40% and 60% ethanol, respectively and their anti-diabetic potentials
      proved by glucose uptake test in HepG2 cells and STZ-induced diabetic rats were
      in the order of saponin rich fraction>flavonoid rich fraction>polysaccharide rich
      fraction. Long-term therapy test (60d) in severe diabetic rats indicated that
      saponin-rich fraction significantly ameliorated clinical symptoms of diabetes
      including the elevated blood glucose, body weight loss as well as the increased
      food and water intake while flavonoid-rich fraction was more potential than
      saponin-rich fraction to increase superoxide dismutase (SOD) activity and
      decrease malondialdehyde (MDA) level in rat plasma. Additionally, saponin-rich
      fraction and flavonoid-rich fraction showed alpha-glycosidase inhibitory activity
      with IC(50) value of 2.05+/-0.32 and 3.92+/-0.65mg/ml, respectively. CONCLUSION:
      The results suggested that saponin in this herb was more important than flavonoid
      in exhibiting anti-diabetic activity and flavonoid contributed more to anti
      oxidant activity in vivo.

PMID- 22366677
TI  - Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch
      (Asteraceae) leaf extract in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Crassocephalum bauchiense have long
      been used in traditional Cameroonian medicine for the treatment of epilepsy,
      pain, inflammatory disorders, arthritis and intestinal pain. AIM OF THE STUDY: In
      this study, we attempted to identify the possible antinociceptive action of the
      aqueous extract and the alkaloid fraction prepared from the leaves of
      Crassocephalum baucheiense. MATERIALS AND METHODS: Using acetic acid induced
      abdominal constrictions, formalin-, capsaisin- and glutamate-induced nociception,
      and hot plate assay procedures, the antinociceptive effects of the aqueous
      extract and the alkaloid fraction was assessed after oral administration in mice.
      Morphine sulfate was used as reference analgesic agent. Mice were submitted to
      the rota-rod task and open-field test in order to assess any non-specific muscle
      relaxant or sedative effects of the extracts of Crassocephalum bauchiense. Male
      and female Swiss mice were used to assess acute toxicity of these extracts.
      RESULTS: The aqueous extract and the alkaloid fraction of Crassocephalum
      bauchiense produced a significant antinociceptive effects in the acetic acid,
      formalin, glutamate, capsaicin and hot plate tests. These antinociceptive effects
      of Crassocephalum bauchiense were significantly attenuated by pretreatment with
      naloxone. The extracts of Crassocephalum bauchiense did not alter the locomotion
      of animals in the open-field or rotarod tests, which suggest a lack of a central
      depressant effect. The animals did not exhibit any acute toxicity to the aqueous
      extract and the alkaloid fraction, so it was not possible to calculate the
      LD(50). CONCLUSION: The results confirm the popular use of Crassocephalum
      bauchiense as an antinociceptive, and contribute to the pharmacological knowledge
      of this species because it was shown that the aqueous extract and the alkaloid
      fraction of Crassocephalum bauchiense produced dose related antinociception in
      models of chemical and thermal nociception through mechanisms that involve an
      interaction with opioidergic pathway.

PMID- 22366678
TI  - Cardioprotective effect of HPLC standardized ethanolic extract of Terminalia
      pallida fruits against isoproterenol-induced myocardial infarction in albino
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia pallida is an evergreen endemic tree,
      mentioned in Ayurveda as the fruits of Terminalia pallida are excellent in
      cardioprotective property. Tribal people use Terminalia pallida fruit for the
      treatment of diabetes and this plant widely used in many other disorders. AIM OF
      STUDY: The present investigation was to evaluate the antioxidant, biochemical
      profile and histological studies of qualitatively standardized ethanolic extract
      of Terminalia pallida fruits (TpFE) against isoproterenol-induced myocardial
      infarction in rats. MATERIALS AND METHODS: TpFE was standardized by high
      performance liquid chromatography (HPLC) and mass spectroscopy (MS). Rats were
      pretreated orally with different doses of TpFE (100, 300, and 500mgkg(-1) body
      weight) and cardioprotective positive control gallic acid (GA) for 30 days prior
      to isoproterenol (ISO) induced myocardial infarction. The rats were sacrificed,
      hearts were collected and homogenized for biochemical analysis. The effects on
      total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol
      (LDL-C) and very low density lipoprotein cholesterol (VLDL-C), high density
      lipoprotein cholesterol (HDL-C), lipid peroxidation (LPO) marker, malondialdehyde
      (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase
      (ALT), aspartate transaminase (AST), catalase (CAT), glutathione peroxidase
      (GPx), sodium potassium (Na(+)/K(+)), calcium (Ca(2+)) and magnesium (Mg(2+))
      adenosine triphosphatases (ATPases) were estimated in heart tissue homogenate.
      RESULTS: Rats administered with ISO showed a significant increase in TC, TG, LDL
      C, VLDL-C, and MDA and a significant decrease in HDL-C, cardiac marker enzymes -
      CK, LDH, ALT and AST. ISO significantly reduced antioxidants - CAT, GPx, and
      membrane bound enzymes - Na(+)/K(+), Ca(2+) and Mg(2+) ATPases. Pretreatment with
      TpFE (100, 300, and 500mgkg(-1) bw) and GA (15mgkg(-1) bw) for a period of 30
      days significantly inhibited the effects of ISO. Moreover, biochemical findings
      were supported by histopathological observations. CONCLUSION: The present study
      provide evidence for the first time, that TpFE pretreatment ameliorated
      myocardial injury in ISO-induced myocardial infarcted rats and exhibited
      cardioprotective activity.

PMID- 22366679
TI  - Medicinal plants used with Thai Traditional Medicine in modern healthcare
      services: a case study in Kabchoeng Hospital, Surin Province, Thailand.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Thai Traditional Medicine (TTM) is available in
      many modern hospitals in Thailand. However, there have been difficulties in
      integrating TTM, particularly the practices of the use of herbal medicines, into
      modern healthcare services. Kabchoeng Hospital is one hospital that has been able
      to overcome these difficulties. Thus, this study aimed to document the successful
      utilization of herbal medicine at Kabchoeng Hospital. The documentation focused
      on both the knowledge of medicinal plants and the success factors that
      facilitated the utilization of herbal medicine in the context of a modern
      hospital in Thailand. MATERIALS AND METHODS: Kabchoeng Hospital was intentionally
      selected for this case study. Participatory observation was used for the data
      collection. There were six groups of key informants: three applied Thai
      Traditional Medicine practitioners (ATTMPs), a pharmacist, two physicians, two
      folk healers, the head of an herbal cultivation and collection group, and 190
      patients. The plant specimens were collected and identified based on the
      botanical literature and a comparison with authentic specimens; these
      identifications were assisted by microscopic and thin layer chromatography (TLC)
      techniques. RESULTS: Eighty-nine medicinal plants were used for the herbal
      preparations. The ATTMPs used these plants to prepare 29 standard herbal
      preparations and occasional extemporaneous preparations. Moreover, in this
      hospital, seven herbal preparations were purchased from herbal medicine
      manufacturers. In total, 36 preparations were used for 10 groups of symptoms,
      such as the treatment of respiratory system disorders, musculo-skeletal system
      disorders, and digestive system disorders. Four success factors that facilitated
      the utilization of herbal medicine at Kabchoeng Hospital were determined. These
      factors included a proper understanding of the uses of herbal medicines, the
      successful integration of the modern and TTM healthcare teams, the support of an
      herbal cultivation and collection group, and the acceptance of the local people.
      CONCLUSIONS: The practices that support the use of herbal medicine at Kabchoeng
      Hospital illustrated the successful application of TTM and also represented a
      model for the integration of TTM, and particularly the use of herbal medicine,
      into modern hospitals. This integration will be beneficial for sustainable
      healthcare systems in Thailand and in other countries where modern medicine is
      the mainstream medical system.

PMID- 22366680
TI  - Oryeongsan (Wulingsan), a traditional Chinese herbal medicine, induces
      natriuresis and diuresis along with an inhibition of the renin-angiotensin
      aldosterone system in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Oryeongsan (ORS, Wulingsan), a formula composed
      of five herbal medicines, has long been used for the treatment of impairments of
      the regulation of body fluid homeostasis in China, Japan and Korea. AIM OF THE
      STUDY: The purpose of the present study was to test the effects of ORS on the
      renal function and the mechanisms involved in rats. MATERIALS AND METHODS:
      Experiments were performed in rats caged individually. Renal function and plasma
      levels of renin activity and aldosterone concentration were measured. RESULTS:
      Treatment of ORS resulted in increases in urinary volume, excretion of Na(+),
      K(+), and Cl(-), and glomerular filtration rate, and decreases in urinary
      osmolality and Na(+) balance. Further, ORS decreased plasma renin activity and
      aldosterone concentration. An increase in urinay excretion of Na(+) was a
      function of glomerular filtration rate, while the increase in the day-time period
      was related with the increase in the ratio of urinary Na(+)/K(+). CONCLUSION:
      Therefore, the present results suggest that ORS induces diuresis and natriuresis
      via inhibition of the renin-angiotensin-aldosterone system in rats.

PMID- 22366681
TI  - Identification and quantification of the major volatile constituents in
      antidepressant active fraction of xiaoyaosan by gas chromatography-mass
      spectrometry.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), a well-known formula for
      relieving depression, was originated from the book of "Taiping Huimin Heji
      Jufang" in Song Dynasty (960-1127 AD), composed of Radix Bupleuri, Radix
      Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae,
      Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose
      proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of
      depression-related syndromes in China. In the formula, Radix Bupleuri usually
      serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba
      serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba
      Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix
      Glycyrrhizae serves as messenger drug, they coordinate with each other and
      enhance the effect of the formula. In our previous experiments, the
      antidepressant effect of XYS was revealed. However, the antidepressant part (or
      component) of this prescription was still obscure. MATERIALS AND METHODS: An
      experimental despair animal model: the mice tail suspension test (TST) was used
      to evaluate the antidepressant activity of XYS and its fractions. GC-MS method
      was developed to identify the volatile components and determine 4 major volatile
      components in active fraction. RESULTS: In the TST test, the effect of a low
      polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile
      compounds in the XY-EA were identified on the basis of standards, isolation and
      structural determination in our laboratory, NIST 05 database and literature data.
      The content of 4 major volatile compounds in XY-EA which is 6.703%. CONCLUSIONS:
      The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4
      major components Z-ligustilide, palmitic acid, atractylenolide I, and
      atractylenolide II may be the antidepressant active compounds.

PMID- 22366682
TI  - Total steroidal alkaloids from Veratrum patulum L. Inhibit platelet aggregation,
      thrombi formation and decrease bleeding time in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Veratrum patulum L. (Liliaceae) is used as one
      source of the Chinese traditional drug "Lilu" which has been used in the
      treatment of aphasia arising from apoplexy, wind type dysentery, headache, etc.
      for thousands of years. AIM OF THE STUDY: To evaluate the antithrombotic effect
      of Veratrum patulum L. (Liliaceae) total steroidal alkaloids (VpA) and explore
      the potential mechanisms. MATERIALS AND METHODS: The antithrombotic effect of VpA
      was evaluated in two experimental thrombosis models in rat. The potential
      antithrombotic mechanisms of VpA were explored by determining the coagulation
      parameters and platelet aggregation induced by various agonists. Cutting-tail rat
      model was used to evaluate the influence of VpA on bleeding time. RESULTS: VpA
      significantly inhibit the formation of arterial and venous thrombosis and showed
      different inhibitory effect on the platelet aggregation induced by various
      agonists with the following potency order: collagen>ADP>thrombin. VpA showed no
      influence on the coagulation parameters in rat. But VpA decreased the cutting
      tail bleeding time in rat. CONCLUSION: VpA possess antithrombotic effect on
      venous and arterial thrombosis. The antithrombotic effect of VpA is due to its
      inhibition to platelet aggregation, especially induced by collagen.

PMID- 22366683
TI  - Antiulcer principle from Zingiber montanum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizome of Zingiber montanum has been extensively
      used as a folk medicine to ameliorate peptic ulcer at northern part of
      Bangladesh. AIM OF THE STUDY: To identify the antiulcer principle of the MeOH
      extract of the rhizome of Zingiber montanum by an ex vivo bioassay guided
      chromatographic separation and purification, and structure elucidation of the
      purified compound by spectroscopic methods. MATERIALS AND METHODS: Dried powder
      of Zingiber montanum rhizomes was extracted with MeOH. The antiulcer activity of
      the crude extract and its chromatographic fractions were evaluated by the
      inhibition of 1N HCl induced gastric lesions in Swiss albino mice. The pure
      compound was purified from the active fraction by crystallization with hexanes.
      Structure of the pure compound was elucidated by spectroscopic methods. The
      antiulcer activity of the pure compound was evaluated by the inhibition of 1N
      HCl, 95% ethanol and indomethacin induced gastric lesions in mice. RESULTS: The
      MeOH extract of Zingiber montanum showed 61.97% and 83.10% inhibition of the 1N
      HCl induced gastric lesions at doses of 200mg/kg and 400mg/kg, respectively, in
      mice. Chromatographic separation on silica gel of the extract was yielded seven
      fractions and the fraction 2 was found to have most potent antiulcer activity in
      mice. This fraction showed 77.46% inhibition of the 1N HCl induced gastric
      lesions at a dose of 40mg/kg in mice. Crystallization of the fraction yielded 1
      (zerumbone, 180mg). It showed statistically 45.77% and 92.25% inhibition of 1N
      HCl induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg,
      respectively. It also showed 29.07% and 45.35% inhibition of 95% ethanol induced
      gastric mucosal damage, and 64.76% and 72.38% inhibition of indomethacin induced
      gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively.
      CONCLUSION: Zerumbone (1) showed potent cytoprotective effect against necrotizing
      agent (HCl) and non-steroidal anti-inflammatory drug (indomethacin) induced
      gastric ulceration. It also exhibited moderate cytoprotective effect against
      noxious agent (EtOH) induced gastric lesions. It can be considered as a promising
      new antiulcer natural drug lead.

PMID- 22366684
TI  - Biomodification to dentin by a natural crosslinker improved the resin-dentin
      bonds.
AB  - OBJECTIVES: Transient collagen cross-linking treatment by proanthocyanidins (PA),
      a natural crosslinker, was proved to increase the cross-linking degree and
      ultimate tensile strength of demineralised dentin. The present study aimed to
      investigate whether transient pretreatment by PA-based preconditioner can improve
      the resin-dentin bonds of various etch and rinse adhesives. The influence of
      solvent type, PA concentration and treatment duration were examined. METHODS: PA
      based preconditioners were prepared by adding powdered grape seed extract, rich
      in PA, to various solvents at different concentrations. They were used on
      demineralised dentin before the application of the bonding agent. Bond strength,
      failure modes and degree of conversion were evaluated via microtensile testing,
      field emission scanning electron microscopy and Fourier transform infrared
      spectroscopy, respectively. RESULTS: Collagen cross-linking treatment by PA-based
      preconditioners presented a concentration- and time-dependent increase in dentin
      bond strength even in reduced, clinically applicable treatment duration. PA
      preconditioning improved bond strength of the tested water/ethanol-based adhesive
      better than the water/acetone-based system. Mixed fracture was the most prevalent
      failure mode happened on the top of the hybrid layer in PA-pretreated specimens,
      whilst at the bottom in non-treated controls. The degree of conversion was not
      significantly affected by PA pretreatment. CONCLUSIONS: Transient PA
      preconditioning improved resin-dentin bonds without compromise on the curing
      behaviours of the tested adhesives.

PMID- 22366685
TI  - Evaluation of separate quantitative radiographic features adds to the prediction
      of incident radiographic osteoarthritis in individuals with recent onset of knee
      pain: 5-year follow-up in the CHECK cohort.
AB  - OBJECTIVE: Detailed radiographic evaluation might enable the identification of
      osteoarthritis (OA) earlier in the disease. This study evaluated whether and
      which separate quantitative features on knee radiographs of individuals with
      recent onset knee pain are associated with incidence of radiographic OA and
      persistence and/or progression of clinical OA during 5-year follow-up. METHOD:
      From the Cohort Hip & Cohort Knee study participants with knee pain at baseline
      were evaluated. Radiographic OA development was defined as Kellgren & Lawrence
      (K&L) grade >= II at 5-year follow-up. Clinical OA was defined as persistent knee
      pain and as progression of Westen Ontario & McMaster Universities Osteoarthritis
      index (WOMAC) pain and function score during follow-up. At baseline radiographic
      damage was determined by quantitative measurement of separate features using Knee
      Images Digital Analysis, and by K&L-grading. RESULTS: Measuring osteophyte area
      [odds ratio (OR) =7.0] and minimum joint space width (OR=0.7), in addition to
      demographic and clinical characteristics, improved the prediction of radiographic
      OA 5 years later [area under curve receiver operating characteristic=0.74 vs 0.64
      without radiographic features]. When the predictive score (based on multivariate
      regression coefficients) was larger than the cut-off for optimal specificity, the
      chance of incident radiographic OA was 54% instead of the prior probability of
      19%. Evaluating separate quantitative features performed slightly better than K&L
      grading (AUC=0.70). Radiographic characteristics hardly added to prediction of
      clinical OA. CONCLUSION: In individuals with onset knee pain, radiographic
      characteristics added to the prediction of radiographic OA development 5 years
      later. Quantitative radiographic evaluation in individuals with suspected OA is
      worthwhile when determining treatment strategies and designing clinical trials.

PMID- 22366686
TI  - Senescence is an endogenous trigger for microRNA-directed transcriptional gene
      silencing in human cells.
AB  - Cellular senescence is a tumour-suppressor mechanism that is triggered by cancer
      initiating or promoting events in mammalian cells. The molecular underpinnings
      for this stable arrest involve transcriptional repression of proliferation
      promoting genes regulated by the retinoblastoma (RB1)/E2F repressor complex.
      Here, we demonstrate that AGO2, RB1 and microRNAs (miRNAs), as exemplified here
      by let-7, physically and functionally interact to repress RB1/E2F-target genes in
      senescence, a process that we call senescence-associated transcriptional gene
      silencing (SA-TGS). Herein, AGO2 acts as the effector protein for let-7-directed
      implementation of silent-state chromatin modifications at target promoters, and
      inhibition of the let-7/AGO2 effector complex perturbs the timely execution of
      senescence. Thus, we identify cellular senescence as the an endogenous signal of
      miRNA/AGO2-mediated TGS in human cells. Our results suggest that miRNA/AGO2
      mediated SA-TGS may contribute to tumour suppression by stably repressing
      proliferation-promoting genes in premalignant cancer cells.

PMID- 22366687
TI  - Single-molecule assays reveal that RNA localization signals regulate dynein
      dynactin copy number on individual transcript cargoes.
AB  - Subcellular localization of mRNAs by cytoskeletal motors plays critical roles in
      the spatial control of protein function. However, optical limitations of studying
      mRNA transport in vivo mean that there is little mechanistic insight into how
      transcripts are packaged and linked to motors, and how the movement of mRNA-motor
      complexes on the cytoskeleton is orchestrated. Here, we have reconstituted
      transport of mRNPs containing specific RNAs in vitro. We show directly that mRNAs
      that are either apically localized or non-localized in Drosophila melanogaster
      embryos associate with the dynein motor and move bidirectionally on individual
      microtubules, with localizing mRNPs exhibiting a strong minus-end-directed bias.
      Single-molecule fluorescence measurements reveal that RNA localization signals
      increase the average number of dynein and dynactin components recruited to
      individual mRNPs. We find that, surprisingly, individual RNA molecules are
      present in motile mRNPs in vitro and provide evidence that this is also the case
      in vivo. Thus, RNA oligomerization is not obligatory for transport. Our findings
      lead to a model in which RNA localization signals produce highly polarized
      distributions of transcript populations through modest changes in motor copy
      number on single mRNA molecules.

PMID- 22366688
TI  - A 14-3-3gamma dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIbeta to
      regulate post-Golgi carrier formation.
AB  - Large pleiomorphic carriers leave the Golgi complex for the plasma membrane by en
      bloc extrusion of specialized tubular domains, which then undergo fission.
      Several components of the underlying molecular machinery have been identified,
      including those involved in the budding/initiation of tubular carrier precursors
      (for example, the phosphoinositide kinase PI(4)KIIIbeta, the GTPase ARF, and
      FAPP2), and in the fission of these precursors (for example, PKD, CtBP1-S/BARS).
      However, how these proteins interact to bring about carrier formation is poorly
      understood. Here, we describe a protein complex that mediates carrier formation
      and contains budding and fission molecules, as well as other molecules, such as
      the adaptor protein 14-3-3gamma. Specifically, we show that 14-3-3gamma dimers
      bridge CtBP1-S/BARS with PI(4)KIIIbeta, and that the resulting complex is
      stabilized by phosphorylation by PKD and PAK. Disrupting the association of these
      proteins inhibits the fission of elongating carrier precursors, indicating that
      this complex couples the carrier budding and fission processes.

PMID- 22366690
TI  - Analysis of cortisol in hair--state of the art and future directions.
AB  - Changes to long-term secretion of the glucocorticoid cortisol are considered to
      play a crucial role in mediating the link between chronic stress and the
      development of numerous immune system related diseases. However, obtaining valid
      assessments of long-term cortisol levels is difficult due to limitations of
      previous measurement strategies in blood, saliva or urine. This review discusses
      evidence on a recent methodological development assumed to provide a considerable
      advancement in this respect: the analysis of cortisol in hair. Being incorporated
      into the growing hair, hair cortisol concentrations (HCC) are assumed to provide
      a retrospective reflection of integrated cortisol secretion over periods of
      several months. Over the past years, supportive evidence has accumulated
      regarding several fundamental characteristics of HCC, including its validity as
      an index of long-term systemic cortisol levels, its reliability across repeated
      assessments and its relative robustness to a range of potential confounding
      influences. Based on this groundwork, research has now also commenced to utilise
      HCC for answering more specific questions regarding the role of long-term
      cortisol secretion in different stress and health-related conditions. The
      possibility of extending hair analysis to also capture long-term secretion of
      other steroid hormones (e.g., androgens or estrogens) provides a further
      intriguing prospect for future research. Given its unique characteristics, the
      use of hair analysis holds great promise to significantly enhance current
      understanding on the role of steroid hormones in psychoimmunological research.

PMID- 22366689
TI  - Lifetime exposure to traumatic psychological stress is associated with elevated
      inflammation in the Heart and Soul Study.
AB  - Exposure to traumatic psychological stress increases risk for disease events and
      mortality in patients with cardiovascular disease (CVD). While the biological
      mechanisms of these effects are not known, inflammation may play a key role as it
      is both elevated by psychological stress and involved in the development and
      progression of CVD. In a prospective study of patients with stable CVD (n=979),
      we examined if higher lifetime trauma exposure was associated with elevated
      levels of inflammation at baseline and at five-year follow-up, and with greater
      increases in inflammation over time. Inflammation was indexed by a composite
      score incorporating the inflammatory markers interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), C-reactive protein (CRP) and resistin. In follow-up
      analyses, we adjusted for sociodemographic factors, psychiatric disorders and
      health behaviors that were significantly associated with trauma exposure. Higher
      trauma exposure was associated with elevated inflammation at baseline (beta=.09,
      p=.01) and at five-year follow-up (beta=.09, p=.03). While levels of inflammation
      increased from baseline to follow-up in the sample, there was no significant
      association between trauma exposure and rate of change in inflammation. Findings
      were robust to adjustments for sociodemographic factors and psychiatric
      disorders, but health behaviors appeared to contribute to the association between
      trauma and inflammation at follow-up. This is the first large-scale demonstration
      of an association between lifetime trauma exposure and inflammation. High
      lifetime exposure to traumatic stress may contribute to an accelerated rate of
      CVD progression through elevated inflammation.

PMID- 22366691
TI  - Simulation of fluid-solid coexistence via thermodynamic integration using a
      modified cell model.
AB  - Despite recent advances, precise simulation of fluid-solid transitions still
      remains a challenging task. Thermodynamic integration techniques are the simplest
      methods to study fluid-solid coexistence. These methods are based on the
      calculation of the free energies of the fluid and the solid phases, starting from
      a state of known free energy which is usually an ideal-gas state. Despite their
      simplicity, the main drawback of thermodynamic integration techniques is the
      large number of states that must be simulated. In the present work, a
      thermodynamic integration technique, which reduces the number of simulated
      states, is proposed and tested on a system of particles interacting via an
      inverse twelfth-power potential energy function. The simulations are implemented
      at constant pressure and the solid phase is modeled according to the constrained
      cell model of Hoover and Ree. The fluid and the solid phases are linked together
      by performing constant-pressure simulations of a modified cell model. The
      modified cell model, which was originally proposed by Hoover and Ree, facilitates
      transitions between the fluid and the solid phase by tuning a homogeneous
      external field. This model is simulated on a constant-pressure path for a series
      of progressively increasing values of the field, thus allowing for direct
      determination of the free energy difference between the fluid and the solid phase
      via histogram reweighting. The size-dependent results are analyzed using
      histogram reweighting and finite-size scaling techniques. The scaling analysis is
      based on studying the size-dependent behavior of the second- and higher-order
      derivatives of the free energy as well as the dimensionless moment ratios of the
      order parameter. The results clearly demonstrate the importance of accounting for
      size effects in simulation studies of fluid-solid transitions.

PMID- 22366692
TI  - Mesquite pod extract modifies the reproductive physiology and behavior of the
      female rat.
AB  - Phytoestrogens are non steroidal compounds that can bind to estrogen receptors,
      mimicking some effects of estradiol (E(2)). These compounds are widespread among
      legumes, which are used as pasture, and their importance in animal agriculture
      has increased. Mesquite (Prosopis sp) is a widespread legume, widely used to feed
      several livestock species in Mexico. The main product of mesquite is the pod,
      which is considered high quality food. As a legume, it could be assumed that
      mesquite contains some amounts of phytoestrogens which might induce potential
      estrogenic effects. However, to our knowledge, there are no reports regarding the
      possible estrogenic activity of this legume either in livestock or in animal
      models such as the rat. Therefore, in this study, we evaluated the potential
      estrogenic effects of mesquite pod extract on several aspects of behavior and
      reproductive physiology of the female rat. The effects of the extract were
      compared with those of E(2) and two isoflavones: daidzein (DAI) and genistein
      (GEN). The following treatments were given to groups of intact and ovariectomized
      (OVX) female rats: vehicle; mesquite pod extract; E(2); GEN; DAI. Compared to
      vehicle groups, mesquite pod extract, DAI, GEN, and E(2) increased uterine weight
      and induced growth in vaginal and uterine epithelia. In intact rats, mesquite pod
      extract, GEN and DAI altered estrous cyclicity, decreased lordotic quotient and
      intensity of lordosis. In OVX rats, mesquite pod extract, DAI and GEN induced
      vaginal estrus, increased vaginal epithelium height, and induced lordosis,
      although its intensity was reduced, compared with intact rats in estrus and E2
      treated rats. These results suggest that mesquite pod extract could have
      estrogenic activity. However, the presence of phytoestrogens in this legume
      remains to be confirmed.

PMID- 22366693
TI  - Fate of invading bacteria in soil and survival of transformants after simulated
      uptake of transgenes, as evaluated by a model system based on lindane
      degradation.
AB  - Emergence of bacteria carrying new traits resulting from mutations, gene
      synthesis by gene-shuffling or acquisition of exogenous DNA underpins the need to
      better understand factors influencing their spread and establishment. Studies of
      soils may be difficult, since the gene of interest is often already present in
      high numbers. The gene linA, responsible for the first dechlorination steps
      during degradation of lindane (gamma-hexachlorocyclohexane), has low background
      levels in soil and is simple to detect. Development of transgenic plants
      containing linA and newly proposed approaches to bioremediation by in situ
      electrotransformation after addition of a vector carrying this gene call for
      documentation on the fate of bacteria that incorporate it. We inserted linA into
      the broad-host-range conjugative RP4-plasmid and transferred it to different soil
      bacteria which were inoculated into soil microcosms in the presence/absence of
      lindane. Similar experiments were performed using Sphingobium francense Sp+,
      which carries all genes for complete lindane degradation. This strain increased
      in numbers during lindane mineralization, but other bacteria increased more,
      resulting in a modified bacterial community structure. The engineered strains
      decreased below the detection limit, but rose in numbers after nutrient addition,
      demonstrating that new invading bacteria may persist in soil in the form of small
      populations over extended time periods.

PMID- 22366694
TI  - Screening of nuclear targeting proteins in Acinetobacter baumannii based on
      nuclear localization signals.
AB  - Nuclear targeting of bacterial proteins is an emerging pathogenic mechanism in
      bacteria. However, due to the absence of an appropriate screening system for
      nuclear targeting proteins, systematic approaches to nuclear targeting of
      bacterial proteins and subsequent host cell pathology are limited. In this study,
      we developed a screening system for nuclear targeting proteins in Acinetobacter
      baumannii using a combination of bioinformatic analysis based on nuclear
      localization signal (NLS) and the Gateway((r)) recombinational cloning system.
      Among 3367 open reading frames of A. baumannii ATCC 17978, 34 functional or
      hypothetical proteins were predicted to carry the putative NLS sequences. Of the
      29 clones generated by the Gateway((r)) recombinational cloning system, 14
      proteins tagged with green fluorescent protein (GFP) were targeted to nuclei of
      host cells. Among the 14 nuclear targeting proteins, S21, L20, and L32 ribosomal
      proteins and transposase carried putative nuclear export signal (NES) sequences,
      but only transposase harbored the functional NES. After translocation to nuclei
      of host cells, four A. baumannii proteins induced cytotoxicity. In conclusion, we
      have developed a screening system for nuclear targeting proteins in A. baumannii.
      This system may open the way to a new field of bacterial pathogenesis.

PMID- 22366696
TI  - The finding of anticardiolipin autoantibodies in patients with pseudoexfoliation
      syndrome requires further evaluation.

PMID- 22366695
TI  - Feasibility study of acupuncture for reducing sleep disturbances and hot flashes
      in postmenopausal breast cancer survivors.
AB  - OBJECTIVES: The present study was a feasibility study of a tailored acupuncture
      intervention in postmenopausal breast cancer survivors (BCSs) reporting sleep
      disturbances and hot flashes. Objectiveswere (1) to describe patterns of
      acupuncture point use; (2) evaluate outcome expectancy, credibility, and
      acceptability relative to the intervention; and (3) evaluate patterns of symptom
      change over time. DESIGN: This was a single-group, nonrandomized, quasi
      experimental 8-week study. SAMPLE/SETTING: Ten BCSs with both sleep disturbances
      and hot flashes were referred to any of 4 Midwestern community acupuncturists.
      METHODS: Assessments were done at baseline (weeks 1, 2), during treatment (weeks
      3, 4), and after treatment (weeks 5, 8). Acupuncture treatment was tailored to
      the individual by community acupuncturists and provided as 3 sessions within a 2
      week period (weeks 3, 4). Patients wore a wrist actigraph during weeks 1, 2, 3,
      4, 5, and 8 and a sternal skin conductance monitor for 24 consecutive hours
      during weeks 1, 2, 3, 4, 5, and 8. Subjective data were obtained by questionnaire
      at weeks 1, 2, 3, 4, 5, and 8. FINDINGS: Women were a mean age of 53 years, with
      an average 6.75 years since diagnosis. A mean of 10 needles were used per
      session, with the most common points located in the lung or lung meridian. Breast
      cancer survivors had high expectancy that acupuncture would decrease their
      symptoms, believed it was a credible treatment, and felt it an acceptable form of
      treatment. Three significant patterns of symptom change were noted from baseline:
      an increase in the number of minutes it took to fall asleep after treatment (from
      week 5 to 8; P = .04), a decrease in the percentage of time awake after sleep
      onset from baseline to follow-up 2 (week 8; P = .05), and a decrease in the
      number of hot flashes from baseline to follow-up 1 (week 5; P = .02).
      IMPLICATIONS FOR NURSING: Findings may be used by clinical nurse specialists to
      consider recommending acupuncture to improve sleep and reduce hot flashes in
      BCSs. CONCLUSIONS: Acupuncture treatment seems to be a feasible treatment option
      for highly motivated BCSs with sleep disturbances and hot flashes but needs to be
      further evaluated in a larger, randomized, controlled clinical trial.

PMID- 22366698
TI  - Cataract surgery in primary angle closure: can it replace iridectomy?

PMID- 22366699
TI  - Plateau iris in open-angle glaucoma?

PMID- 22366701
TI  - The effect of mitomycin C in the management of bleb failure.

PMID- 22366702
TI  - Comparison of optic nerve head parameter measurements obtained by time-domain and
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To compare the measurements of the optic nerve head (ONH) parameters
      provided by time-domain (TD) and spectral-domain (SD) optical coherence
      tomography (OCT). METHODS: Four ONH parameters were analyzed: optic disc area,
      rim area, cup-to-disc area ratio (CDR), and vertical cup-to-disc ratio (VCDR).
      Stratus OCT and Cirrus HD-OCT were used to obtain measurements by TD-OCT and SD
      OCT, respectively. Stratus OCT measurements were collected before and after
      manual correction of the ONH edges. RESULTS: Twenty healthy participants and 20
      patients with glaucomatous eyes were enrolled. Although manual correction of
      Stratus OCT measurements reduced the differences compared with Cirrus HD-OCT, the
      latter measured a smaller mean disc area than Stratus OCT in healthy (2.02+/-0.31
      vs. 2.18+/-0.29 mm2, P=0.0003) and glaucomatous eyes (1.92+/-0.35 vs. 2.19+/-0.38
      mm2, P<0.0001). Cirrus HD-OCT measured a smaller rim area than Stratus OCT in
      healthy (1.31+/-0.30 vs. 1.56+/-0.32 mm2, P<0.0001) and glaucomatous eyes (0.80+/
      0.25 vs. 0.97+/-0.36 mm2, P=0.0052), a higher CDR (0.55+/-0.11 vs. 0.49+/-0.11,
      P<0.0001) and VCDR in healthy eyes (0.55+/-0.11 vs. 0.49+/-0.11, P<0.0001), and a
      higher CDR in glaucomatous eyes (0.74+/-0.10 vs. 0.58+/-0.18, P<0.0001). No
      statistically significant differences were detected for VCDR in glaucomatous
      eyes. All measured values showed good correlation (r>=0.70). Large 95% limits of
      agreement between the 2 devices were found for most parameters. CONCLUSIONS: ONH
      parameter measurements provided by TD-OCT and SD-OCT show significant differences
      and cannot be considered interchangeable.

PMID- 22366703
TI  - Influence of corneal biomechanical properties on intraocular pressure differences
      between an air-puff tonometer and the Goldmann applanation tonometer.
AB  - PURPOSE: To estimate the influence of corneal properties on intraocular pressure
      (IOP) differences between an air-puff tonometer (NT530P; Nidek) and the Goldmann
      applanation tonometer (Haag-Streit). PATIENTS AND METHODS: The influence of
      central corneal thickness (CCT), keratometry, and Ocular Response Analyzer
      (Reichert) measurements of corneal viscoelasticity [corneal hysteresis (CH) and
      corneal resistance factor (CRF)] on IOP differences between tonometers was
      evaluated. RESULTS: The CRF was calculated to be the best predictor of the
      differences in IOP readings between tonometers (r2=0.23; P<0.001), followed by
      CCT (r2=0.15; P=0.003) and CH (r2=0.14; P=0.003). Keratometry performed very
      poorly as lone predictor of IOP differences. In a multiple regression model, CRF,
      CH, and CCT together accounted for 25% (r2=0.25; P<0.01) of the variance in IOP
      reading differences between tonometers. CONCLUSIONS: Corneal resistance to
      applanation induced by either contact or noncontact tonometers was calculated to
      be the most determinant factor in influencing IOP differences between applanation
      tonometers.

PMID- 22366704
TI  - The impact of corneal edema on intraocular pressure measurements using goldmann
      applanation tonometry, Tono-Pen XL, iCare, and ORA: an in vitro model.
AB  - PURPOSE: Among other corneal biomechanical properties, Goldmann applanation
      tonometry (GAT) has been shown to depend on corneal edema. New tonometry devices
      have been designed, such as the Tono-Pen XL, iCare, and ocular response analyzer
      (ORA), to measure the intraocular pressure (IOP) accurately. This study aims to
      investigate the influence of corneal edema on the accuracy of these IOP-measuring
      devices in an in vitro model. METHODS: A model of an artificial anterior chamber
      was developed using a guided trephination system. Eight donor corneas not
      suitable for keratoplasty were clamped into this artificial anterior chamber. All
      corneas showed signs of stromal edema. Intracameral pressure (ICP) was adjusted
      manometrically to 10, 20, 30, 40, and 50 mm Hg. The central corneal thickness
      (CCT) was determined by ultrasonic pachymetry. For each manometrically defined
      ICP, tonometry was performed using the iCare, Tono-Pen XL, GAT, and ORA. RESULTS:
      The mean CCT increased from 616.1+/-29.6 um to 626.9+/-36.1 um. At 10 mm Hg, GAT
      yielded a higher ICP than those manometrically adjusted (10.4+/-3.3 mm Hg); at
      all other ICP levels, GAT yielded lower ICP levels than those adjusted. The Tono
      Pen XL and iCare showed the greatest difference at 10 mm Hg, with the Tono-Pen XL
      yielding a value of 14.0+/-4.0 mm Hg and the iCare yielding a value of 12.5+/-2.6
      mm Hg. All other results of the 2 devices fell within a range of +/-2 mm Hg from
      the adjusted ICP. The ORA provided accurate results only at "physiological" ICP
      levels with a maximum difference of 2.6 mm Hg at 30 mm Hg. At higher ICP levels,
      corneal hysteresis decreased significantly with increasing ICP. None of the
      measurement devices revealed a statistically relevant dependence on CCT in this
      experimental setting. CONCLUSIONS: The Tono-Pen XL and the iCare yielded the most
      accurate ICP values across all the adjusted ICP values. This may be because of
      their relatively small contact area with the cornea and, consequently, greater
      independence from corneal biomechanical properties. The ORA yielded accurate
      measurement results only at physiological ICP levels. As anticipated, GAT
      underestimated ICP. The Tono-Pen XL and the iCare should therefore be used to
      determine IOP in patients suffering from corneal edema, such as bullous
      keratopathy or Fuchs endothelial dystrophy.

PMID- 22366705
TI  - Relationship between ocular pulse amplitude and glaucomatous central visual field
      defect in normal-tension glaucoma.
AB  - PURPOSE: To investigate the relationship between central visual field (VF)
      defects and ocular pulse amplitude (OPA) in early normal-tension glaucoma (NTG).
      PATIENTS AND METHODS: This retrospective study included 100 eyes of 100 subjects:
      54 NTG patients whose mean deviations were better than -7.00 dB and 46 normal
      subjects. OPA was measured by dynamic contour tonometry. NTG patients were
      divided into 2 subgroups according to VF tests: the central VF-invading and the
      central VF-sparing groups. Ocular parameters including OPA, intraocular pressure
      (IOP), and indices of VF tests were analyzed in glaucoma patients and normal
      subjects. RESULTS: There was no difference in the OPA between the NTG and normal
      groups. However, IOP and OPA of the central VF-invading group (14.4 +/- 2.87 and
      2.9 +/- 0.78 mm Hg) were higher than those of the central VF-sparing group (12.7
      +/- 2.52 and 2.0 +/- 0.80 mm Hg; P = 0.025 and P < 0.001, respectively). OPA, but
      not IOP, showed a positive correlation with the VF test indices that represented
      central field defects (r = 0.494, P < 0.001). CONCLUSIONS: Increased OPA was
      related to more centrally located VF defects in NTG patients with mild VF
      defects.

PMID- 22366706
TI  - The contributing role of the intestinal microbiota in stressor-induced increases
      in susceptibility to enteric infection and systemic immunomodulation.
AB  - The body is colonized by highly complex and genetically diverse communities of
      microbes, the majority of which reside within the intestines in largely stable
      but dynamically interactive climax communities. These microbes, referred to as
      the microbiota, have many functions that enhance the health of the host, and it
      is now recognized that the microbiota influence both mucosal and systemic
      immunity. The studies outlined in this review demonstrate that the microbiota are
      also involved in stressor-induced immunomodulation. Exposure to different types
      of stressors, including both physical and psychological stressors, changes the
      composition of the intestinal microbiota. The altered profile increases
      susceptibility to an enteric pathogen, i.e., Citrobacter rodentium, upon oral
      challenge, but is also associated with stressor-induced increases in innate
      immune activity. Studies using germfree mice, as well as antibiotic-treated mice,
      provide further evidence that the microbiota contribute to stressor-induced
      immunomodulation; stressor-induced increases in splenic macrophage microbicidal
      activity fail to occur in mice with no, or reduced, intestinal microbiota. While
      the mechanisms by which microbiota can impact mucosal immunity have been studied,
      how the microbiota impact systemic immune responses is not clear. A mechanism is
      proposed in which stressor-induced degranulation of mucosal mast cells increases
      the permeability of the intestines. This increased permeability would allow
      intact bacteria and/or bacterial products (like peptidoglycan) to translocate
      from the lumen of the intestines to the interior of the body, where they
      directly, or indirectly, prime the innate immune system for enhanced reactivity
      to antigenic stimulation.

PMID- 22366707
TI  - Neonatal immune challenge alters reproductive development in the female rat.
AB  - Neonatal lipopolysaccharide (LPS) exposure alters neuroendocrine, immune and
      behavioural responses in adult rats. Recent findings indicate that neonatal LPS
      treatment may have a more pronounced effect on the mating behaviours of females
      compared to males. The current study further explored the impact of neonatal
      inflammation on reproductive development in the female rat. Wistar rats were
      administered LPS (0.05 mg/kg, i.p.) or saline (equivolume) on postnatal days
      (PNDs) 3 and 5. The immediate effect of treatment was assessed on plasma
      corticosterone and tyrosine hydroxylase (TH) phosphorylation in the adrenal
      medulla. Weight gain and vaginal opening were recorded, and oestrous cyclicity
      was monitored post-puberty and in late adulthood. Blood and ovaries were
      collected throughout development to assess HPA and HPG hormones and to examine
      ovarian morphology. Reproductive success in the first (F1) generation and
      reproductive development in the second (F2) generation were also assessed.
      Neonatal LPS exposure resulted in increased TH phosphorylation in the neonatal
      adrenals. LPS treatment increased the corticosterone concentrations of females as
      juveniles, adolescents and adults, and reduced FSH in adolescence. Increased
      catch-up growth was evident in LPS-treated females, prompting earlier onset of
      puberty. Diminished follicular reserve was observed in neonatally LPS-treated
      females along with the advanced reproductive senescence. While fertility rates
      were not compromised, higher mortality and morbidity were observed in litters
      born to LPS-treated mothers. Female offspring of LPS-treated mothers displayed
      increased corticosterone on PND 14, increased catch-up growth and delayed
      emergence of the first oestrous cycle. No differences in any of the parameters
      assessed were observed in F2 males. These data suggest that neonatal
      immunological challenge has a profound impact on the female reproductive
      development, via the alteration of metabolic and neuroendocrine factors which
      regulate sexual maturation. Evidence of altered development in the female, but
      not male offspring of LPS-treated dams suggests increased susceptibility of
      females to the deleterious effects of neonatal immunological stress and its
      possible transferability to a subsequent generation.

PMID- 22366708
TI  - Target contrast affects reaching and grasping in the visually impaired subjects.
AB  - PURPOSE: The aim of this study is to investigate whether subjects with central
      visual impairment (VI) show different reaching and grasping behavior for targets
      of different contrasts compared with visually normal age-matched subjects.
      METHODS: Reaching and grasping performance was measured in 14 subjects with VI
      and 14 normal subjects. Subjects were asked to pick up a cylindrical target.
      Three different targets were used: black (low contrast), white (high contrast),
      and transparent, placed against a black background. A motion analysis system
      (Vicon 460) recorded and reconstructed the hand and finger movements. RESULTS:
      Significantly longer onset times, total movement duration, and time after maximum
      grip aperture were obtained for subjects with VI compared with normal subjects (p
      < 0.002). No significant differences existed in maximum velocity and grip
      aperture between the two groups for any of the targets. CONCLUSIONS: Subjects
      with VI took longer to initiate and to complete the movement. Maximum velocity
      and grip aperture were not different suggesting that once the target was "seen"
      by subjects with VI performance was similar to normal subjects. Time after
      maximum grip aperture was longer in subjects with VI indicating the need for
      "online" modifications in these subjects. Contrast sensitivity was significantly
      correlated to more indices than visual acuity.

PMID- 22366709
TI  - Scoring of progressive power lenses by means of user power maps.
AB  - PURPOSE: A progressive power lens (PPL) has a relatively complex power
      distribution, with regions for far, intermediate, and near vision, and also
      regions affected by aberrations, mainly astigmatism and defocus. Scoring
      techniques (Sheedy, Optom Vis Sci 2004;81:350-61) have been proposed to mark and
      classify PPLs according to their optical performance at each region. The
      objective of this study is to show that although scoring is useful to compare
      different lens designs, its outcome is highly dependent on the way power is
      defined and/or computed. METHODS: To demonstrate this, the progressive surfaces
      of many different current designs have been measured with a profiler. From these
      measurements and by means of exact ray tracing techniques, we obtain both the
      power maps that we would measure with a focimeter or a typical lens mapper and
      the power maps that the user perceives at the actual position of use. The scoring
      technique from Sheedy has then been applied to both types of maps. RESULTS: It is
      shown that the parameters that define the characteristics of a PPL when the power
      map is measured with a standard mapper are not significantly associated with the
      actual performance of the lens when it is fitted. In a similar way, it is shown
      that two lenses that have been optimized according to the same target power
      distribution may get completely different marks depending on the definition of
      power that has been used in the optimization process. We also propose a graphical
      method to easily grasp the overall PPL performance by simultaneously presenting
      four-dimensional information from the scoring technique. CONCLUSIONS: Although in
      general Sheedy's test is an important tool to compare different PPL designs, it
      cannot be used to compare those designs optimized for improving user power from
      classical front side designs when power has been measured for both types of
      designs with a standard focimeter.

PMID- 22366710
TI  - Useful field of view predicts driving in the presence of distracters.
AB  - PURPOSE: The Useful Field of View (UFOV) test has been shown to be highly
      effective in predicting crash risk among older adults. An important question
      which we examined in this study is whether this association is due to the ability
      of the UFOV to predict difficulties in attention-demanding driving situations
      that involve either visual or auditory distracters. METHODS: Participants
      included 92 community-living adults (mean age 73.6 +/- 5.4 years; range 65-88
      years) who completed all three subtests of the UFOV involving assessment of
      visual processing speed (subtest 1), divided attention (subtest 2), and selective
      attention (subtest 3); driving safety risk was also classified using the UFOV
      scoring system. Driving performance was assessed separately on a closed-road
      circuit while driving under three conditions: no distracters, visual distracters,
      and auditory distracters. Driving outcome measures included road sign
      recognition, hazard detection, gap perception, time to complete the course, and
      performance on the distracter tasks. RESULTS: Those rated as safe on the UFOV
      (safety rating categories 1 and 2), as well as those responding faster than the
      recommended cut-off on the selective attention subtest (350 msec), performed
      significantly better in terms of overall driving performance and also experienced
      less interference from distracters. Of the three UFOV subtests, the selective
      attention subtest best predicted overall driving performance in the presence of
      distracters. CONCLUSIONS: Older adults who were rated as higher risk on the UFOV,
      particularly on the selective attention subtest, demonstrated poorest driving
      performance in the presence of distracters. This finding suggests that the
      selective attention subtest of the UFOV may be differentially more effective in
      predicting driving difficulties in situations of divided attention which are
      commonly associated with crashes.

PMID- 22366711
TI  - Eye-related pain induced by visually demanding computer work.
AB  - PURPOSE: Eye strain during visually demanding computer work may include glare and
      increased squinting. The latter may be related to elevated tension in the
      orbicularis oculi muscle and development of muscle pain. The aim of the study was
      to investigate the development of discomfort symptoms in relation to muscle
      activity and muscle blood flow in the orbicularis oculi muscle during computer
      work with visual strain. METHODS: A group of healthy young adults with normal
      vision was randomly selected. Eye-related symptoms were recorded during a 2-h
      working session on a laptop. The participants were exposed to visual stressors
      such as glare and small font. Muscle load and blood flow were measured by
      electromyography and photoplethysmography, respectively. RESULTS: During 2 h of
      visually demanding computer work, there was a significant increase in the
      following symptoms: eye-related pain and tiredness, blurred vision, itchiness,
      gritty eyes, photophobia, dry eyes, and tearing eyes. Muscle load in orbicularis
      oculi was significantly increased above baseline and stable at 1 to 1.5% maximal
      voluntary contraction during the working sessions. Orbicularis oculi muscle blood
      flow increased significantly during the first part of the working sessions before
      returning to baseline. There were significant positive correlations between eye
      related tiredness and orbicularis oculi muscle load and eye-related pain and
      muscle blood flow. Subjects who developed eye-related pain showed elevated
      orbicularis oculi muscle blood flow during computer work, but no differences in
      muscle load, compared with subjects with minimal pain symptoms. CONCLUSIONS:
      Eyestrain during visually demanding computer work is related to the orbicularis
      oculi muscle. Muscle pain development during demanding, low-force exercise is
      associated with increased muscle blood flow, possible secondary to different
      muscle activity pattern, and/or increased mental stress level in subjects
      experiencing pain compared with subjects with minimal pain.

PMID- 22366712
TI  - Down-regulation of the serotonin transporter in hyperreactive platelets
      counteracts the pro-thrombotic effect of serotonin.
AB  - An elevated plasma concentration of serotonin ([5-HT]) is a common feature of
      cardiovascular disease often associated with enhanced platelet activation and
      thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent
      risk factor for platelet hyperreactivity or only is an epiphenomenon of
      cardiovascular disease is poorly understood. We examined in vitro and in vivo
      platelet function following a 24h elevation of plasma [5-HT] in mice. In vivo
      administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated
      mice compared to control mice instrumented with saline loaded pumps. 5-HT
      infusion did not increase systolic blood pressure, but markers of platelet
      activation including P-selectin and (PE)Jon/A staining were increased and these
      findings coincided with the enhanced aggregation of isolated platelets in
      response to type I fibrillar collagen. Tail bleeding times and the time to
      occlusion following chemical damage to the carotid artery were shortened in 5-HT
      infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT
      uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and
      attenuated platelet activation and aggregation. These results and our biochemical
      indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused
      mice reveal a mechanistic link between elevated plasma [5-HT], abnormal
      intracellular 5-HT signaling and accentuated platelet aggregation. Although a
      down-regulation of the serotonin transporter (SERT) on the platelet surface may
      counteract the pro-thrombotic influence of elevated plasma [5HT], this
      compensatory mechanism may fail to prevent the increased thrombotic risk caused
      by elevated plasma [5-HT].

PMID- 22366713
TI  - ATP acts as a survival signal and prevents the mineralization of aortic valve.
AB  - Calcific aortic valve disease (CAVD) is a disorder related to progressive
      mineralization of valvular tissue that is a leading cause of heart disease. Thus
      far, there is no medical treatment to prevent the mineralization of aortic
      valves. It is generally thought that pathologic mineralization is linked to
      apoptosis of vascular cells. However, the role of apoptosis during mineralization
      as well as the survival signals for valvular interstitial cells (VICs), the main
      cellular component of aortic valves, remains to be identified. Here, through
      several lines of evidence, we show that bioavailability of extracellular ATP is a
      signal which determines survival or apoptosis of VICs and, in doing so, plays a
      major role in the development of CAVD. Specifically, in CAVD and in VIC cultures
      undergoing mineralization, we found a high level of the ectonucleotidase ENPP1.
      In addition, a genetic polymorphism in the intron 9 of the ENPP1 gene was
      associated with CAVD in a case-control cohort as well as with mRNA expression
      levels of ENPP1 in aortic valves. A high level of ENPP1 in CAVD promoted
      apoptosis-mediated mineralization of VICs by depleting the extracellular pool of
      ATP. We then documented that release of ATP by VICs promoted cell survival via
      the P2Y(2) receptor and the PI3K/Akt signaling pathway. Hence, our results show
      that level of ENPP1 modulates extracellular concentration of ATP, which is an
      important survival signal for VICs. These findings may help to develop novel
      pharmacological treatment for CAVD.

PMID- 22366715
TI  - Research agenda for tackling inequalities related to migration and ethnicity in
      Europe.
AB  - Reducing ethnic inequalities and inequities in health needs to become a higher
      priority for public health research. Active involvement of migrant and ethnic
      minority populations in European population health research is necessary, for
      data show important inequalities but evidence, particularly on effectiveness, is
      sparse and strategic overviews rarer still. Ethnically disaggregated health
      surveillance systems are developing slowly, and pragmatically, often using
      country of birth. The principles to adopt, given the gaps between the ideal and
      the current reality, need wider discussion. Ethics may provide both principles
      and impetus. Doing no harm, doing good, respecting the research participants'
      autonomy are good starting points. More emphasis is needed on justice, fairness
      and equality, participation and communicating effectively. Ethnic minority groups
      are willing participants in trials once linguistic and trust-related barriers are
      overcome, though recruitment costs are higher. Guidelines and strategies by
      European bodies with research funding or enforcement responsibilities are needed.
      The research community needs an infrastructure within which to collect and
      utilize evidence. Research can help migrant and ethnic minority groups to
      participate more fully in our multi-ethnic societies.

PMID- 22366716
TI  - Successful treatment of Cryptococcus gattii neurocryptococcosis in a 5-year-old
      immunocompetent child from the French Guiana Amazon region.
AB  - Compared to the incidence in adults, cryptococcosis is rare among children. We
      report a case of neurocryptococcosis due to Cryptococcus gattii in a five-year
      old girl without identified risk factors living in French Guiana. Neurological
      surgery in combination with long-term antifungal treatment with amphotericin B
      and 5-flucytosine successfully resolved the cryptococcal infection. Subsequent
      molecular characterization of the Cryptococcus isolate revealed that the
      infection was caused by a C. gattii genotype AFLP6B/VGIIb strain.

PMID- 22366714
TI  - Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for
      oxidative-nitrosative stress.
AB  - Peripheral neuropathy develops in human subjects with prediabetes and metabolic
      syndrome before overt hyperglycemia. The contributions of impaired glucose
      tolerance and insulin signaling, hypertriglyceridemia and/or increased
      nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition
      remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor
      effect on glucose homeostasis. This study evaluated the roles of impaired glucose
      tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty
      (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of
      hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. Sixteen
      week-old Zucker fatty rats with impaired glucose tolerance, obesity,
      hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA
      displayed sensory nerve conduction velocity deficit, thermal and mechanical
      hypoalgesia, and tactile allodynia. Acipimox (100 mg kg(-1) day(-1), 4 weeks)
      reduced serum insulin, NEFA, and triglyceride concentrations without affecting
      glucose tolerance and hypercholesterolemia. It alleviated sensory nerve
      conduction velocity deficit and changes in behavioral measures of sensory
      function and corrected oxidative-nitrosative stress, but not impaired insulin
      signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial
      superoxide production and NAD(P)H oxidase activity in cultured human Schwann
      cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations
      cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering
      agents and antioxidants may find a use in the management of this condition.

PMID- 22366717
TI  - Phenotypic and molecular identification of Coccidioides posadasii in a patient
      evaluated for bilateral lung transplantation.
AB  - BACKGROUND: Coccidioidomycosis is an endemic fungal infection caused by
      Coccidioides immitis and Coccidioides posadasii. It can be particularly severe in
      transplant recipients that have a current or a previous coccidioidal infection.
      Fatal case of coccidioidomycosis has been described in this group of patients.
      AIMS: We report a severe case of pneumonia caused by C. posadassi in a 29 year
      old white woman that had been admitted to hospital as part of the evaluation for
      bilateral lung transplantation. The patient was a native and resident of
      Catamarca, Argentina. Molecular methodologies contributed to the species
      identification. METHODS: Clinical, laboratory records and microbiological tests
      were carried out to diagnose the infection and to identify C. posadasii. RESULTS:
      A fungus was isolated from BAL culture. Phenotypic characterization, specific PCR
      and experimental animal inoculation demonstrated the presence of C. posadasii.
      The patient responded well to amphotericin B deoxycholate. Lung transplantation
      was postponed. CONCLUSIONS: Specific PCR can be an important alternative for the
      correct identification of C. immitis or C. posadasii in laboratories with
      implemented molecular biology tools. This case emphasizes the need for a
      systematic assessment in organ transplant units of patients inhabiting endemic
      areas of coccidioidomycosis.

PMID- 22366718
TI  - Antifungal activity of altenusin isolated from the endophytic fungus Alternaria
      sp. against the pathogenic fungus Paracoccidioides brasiliensis.
AB  - BACKGROUND: Altenusin is a biphenyl derivative isolated from different species of
      fungi, which presents several biological activities. AIMS: We report the
      antifungal activity of the altenusin isolated from the endophytic fungus
      Alternaria sp., against clinical isolates of Paracoccidioides brasiliensis, and
      its action on cell walls of P. brasiliensis and the nonpathogenic yeast
      Schizosaccharomyces pombe. METHODS: In vitro antifungal activity of altenusin was
      evaluated using the broth microdilution method against 11 strains of P.
      brasiliensis and one strain of S. pombe. The effects of the altenusin on the cell
      wall were estimated using the sorbitol protection assay. RESULTS: The altenusin
      presented strong activity against P. brasiliensis with MIC values ranging between
      1.9 and 31.2 MUg/ml, and 62.5 MUg/ml for S. pombe. Our results demonstrated that
      the MIC values for altenusin were increased for P. brasiliensis Pb18 and for S.
      pombe when the medium was supplemented with sorbitol. Additionally, S. pombe
      cells treated with altenusin were more rounded in shape than untreated cells.
      CONCLUSIONS: Altenusin showed activity against clinical strains of P.
      brasiliensis at the concentration tested, and this compound probably affects
      fungal cell walls. These findings suggest that altenusin could act through the
      inhibition of cell wall synthesis or assembly in P. brasiliensis and S. pombe,
      and could be considered as a lead compound for the design of new antifungals.

PMID- 22366719
TI  - A comparison of outcomes of out-of-hospital cardiac arrest with non-cardiac
      etiology between emergency departments with low- and high-resuscitation case
      volume.
AB  - OBJECTIVES: It is unclear whether outcome after out-of-hospital cardiac arrest
      (OHCA) of non-cardiac etiology (NCE) is associated with the volume of patients
      with OHCA received annually at the emergency department (ED) where they receive
      treatment. This study evaluated whether the volume of patients treated is
      associated with better outcomes for non-cardiac OHCA patients. METHODS: This
      study was performed in an emergency medical service (EMS) system with a single
      tiered basic-to-intermediate service level and approximately 410 destination
      hospitals for eligible OHCA cases. A nationwide OHCA database (2006-2008),
      constructed from EMS run sheets, and a hospital medical record review were used.
      OHCA was defined as pulseless and unresponsive in the field. Included in the
      study were cases treated with OHCA whose etiology was non-cardiac. Excluded were
      cases with unknown hospital outcome. The cutoff number for a high volume (HV)
      versus a low volume (LV) of cardiopulmonary resuscitation (CPR) cases was
      calculated using a threshold model. The primary end points were survival to
      admission and survival to discharge. The adjusted odds ratios (ORs) and 95%
      confidence intervals (95% CIs) for the endpoints were calculated, adjusting for
      potential predictors. RESULTS: There were 10,425 eligible patients (trauma 5735;
      drowning 98; poisoning 684; asphyxia 1413; and hanging 1605). The survival-to
      admission and the survival-to-discharge rates of the study participants were 9.6%
      and 2.4%, respectively. The cutoff number for case volume was 38 per year. The
      rates of survival to admission and survival to discharge were significantly
      higher in the HV (18.6% and 5.1%, respectively) group when compared to the LV
      group (5.9% and 1.3%, respectively). For the treated, non-cardiac OHCA patients,
      the adjusted ORs in the HV group compared to the LV group were 2.16 for survival
      to admission (95% CI: 1.84-2.55) and 2.58 for survival to discharge (95% CI: 1.90
      3.52). The survival-to-discharge rate was significantly higher in the HV group
      than in the LV group for each cause: trauma 2.1% vs. 0.6%, drowning 6.8% vs.
      1.9%, poisoning 8.6% vs. 1.7%, asphyxia 13.5% vs. 3.8%, and hanging 5.2% vs.
      1.3%, respectively. CONCLUSION: This national cohort study suggests that greater
      survival to admission as well as discharge for patients with OHCA of NCE is
      associated with greater annual volume of patients with OHCA treated at that
      hospital.

PMID- 22366720
TI  - The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A.
AB  - Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the
      sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular
      peptide backbone that is additionally restrained by three unusual thioether bonds
      between three cysteines and the alpha-carbon of one threonine and two
      phenylalanines, respectively. In this study, we demonstrate that these bonds are
      synthesized by the radical S-adenosylmethionine enzyme AlbA, which is encoded by
      the sbo-alb operon and comprises two [4Fe-4S] clusters. One [4Fe-4S] cluster is
      coordinated by the prototypical CXXXCXXC motif and is responsible for the
      observed S-adenosylmethionine cleavage reaction, whereas the second [4Fe-4S]
      cluster is required for the generation of all three thioether linkages. On the
      basis of the obtained results, we propose a new radical mechanism for thioether
      bond formation. In addition, we show that AlbA-directed substrate transformation
      is leader-peptide dependent, suggesting that thioether bond formation is the
      first step during subtilosin A maturation.

PMID- 22366721
TI  - Regulation of nuclear PKA revealed by spatiotemporal manipulation of cyclic AMP.
AB  - Understanding how specific cyclic AMP (cAMP) signals are organized and relayed to
      their effectors in different compartments of the cell to achieve functional
      specificity requires molecular tools that allow precise manipulation of cAMP in
      these compartments. Here we characterize a new method using bicarbonate
      activatable and genetically targetable soluble adenylyl cyclase to control the
      location, kinetics and magnitude of the cAMP signal. Using this live-cell cAMP
      manipulation in conjunction with fluorescence imaging and mechanistic modeling,
      we uncovered the activation of a resident pool of protein kinase A (PKA)
      holoenzyme in the nuclei of HEK-293 cells, modifying the existing dogma of cAMP
      PKA signaling in the nucleus. Furthermore, we show that phosphodiesterases and A
      kinase anchoring proteins (AKAPs) are critical in shaping nuclear PKA responses.
      Collectively, our data suggest a new model in which AKAP-localized
      phosphodiesterases tune an activation threshold for nuclear PKA holoenzyme,
      thereby converting spatially distinct second messenger signals to temporally
      controlled nuclear kinase activity.

PMID- 22366722
TI  - An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating
      ubiquitination.
AB  - The anaphase-promoting complex/cyclosome (APC) is a ubiquitin ligase that is
      required for exit from mitosis. We previously showed that tosyl arginine methyl
      ester (TAME) inhibits APC-dependent proteolysis by competing with the C-terminal
      isoleucine-arginine tail of the APC activator cell division cycle 20 (Cdc20) for
      APC binding. Here we show that in the absence of APC substrates, TAME ejects
      Cdc20 from the APC by promoting Cdc20 autoubiquitination in its N-terminal
      region. Cyclin B1 antagonizes TAME's effect by promoting binding of free Cdc20 to
      the APC and by suppressing Cdc20 autoubiquitination. Nevertheless, TAME
      stabilizes cyclin B1 in Xenopus extracts by two mechanisms. First, it reduces the
      k(cat) of the APC-Cdc20-cyclin B1 complex without affecting the K(m), slowing the
      initial ubiquitination of unmodified cyclin B1. Second, as cyclin B1 becomes
      ubiquitinated, it loses its ability to promote Cdc20 binding to the APC in the
      presence of TAME. As a result, cyclin B1 ubiquitination terminates before
      reaching the threshold necessary for proteolysis.

PMID- 22366725
TI  - A heterotrimetallic Pd-Sm-Pd complex for asymmetric Friedel-Crafts alkylations of
      pyrroles with nitroalkenes.
AB  - Catalytic asymmetric Friedel-Crafts alkylations of pyrroles and nitroalkenes were
      carried out by using a novel heterotrimetallic Pd-Sm-Pd catalyst based on a
      simple chiral ligand 1, to give the adducts with high yields and up to 93% ee.

PMID- 22366723
TI  - Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against
      aggregation.
AB  - Oligomerization of tau is a key process contributing to the progressive death of
      neurons in Alzheimer's disease. Tau is modified by O-linked N-acetylglucosamine
      (O-GlcNAc), and O-GlcNAc can influence tau phosphorylation in certain cases. We
      therefore speculated that increasing tau O-GlcNAc could be a strategy to hinder
      pathological tau-induced neurodegeneration. Here we found that treatment of
      hemizygous JNPL3 tau transgenic mice with an O-GlcNAcase inhibitor increased tau
      O-GlcNAc, hindered formation of tau aggregates and decreased neuronal cell loss.
      Notably, increases in tau O-GlcNAc did not alter tau phosphorylation in vivo.
      Using in vitro biochemical aggregation studies, we found that O-GlcNAc
      modification, on its own, hinders tau oligomerization. O-GlcNAc also inhibits
      thermally induced aggregation of an unrelated protein, TAK-1 binding protein,
      suggesting that a basic biochemical function of O-GlcNAc may be to prevent
      protein aggregation. These results also suggest O-GlcNAcase as a potential
      therapeutic target that could hinder progression of Alzheimer's disease.

PMID- 22366726
TI  - Antagonistic modulatory influences of negative affect on cognitive control:
      Reduced and enhanced interference resolution capability after the induction of
      fear and sadness.
AB  - The present behavioral study investigated the influence of negative affect on the
      neural mechanisms of cognitive control. We expected to find evidence for an
      antagonistic modulation of cognition by threat-relevant and threat-irrelevant
      negative affect (i.e. fear and sadness) that should promote bottom-up monitoring
      and top-down selection, respectively. Subjects performed one of three conflict
      tasks (Stroop, Flanker, or Simon) that tap distinct control mechanisms of
      conflict resolution, comprising specific attentional and motor control processes.
      On each task trial, target stimuli were preceded by a face stimulus exhibiting a
      fearful, sad, or neutral expression, providing three affect conditions. Our data
      provides strong evidence for substantially increased selection (attentional and
      motor selection) after priming of threat-irrelevant negative affect (sadness).
      Deviating from the results of previous studies, our analysis did not consistently
      yield increased monitoring after fear priming. We discuss these findings with
      respect to the effectiveness of different experimental affect priming procedures
      (i.e. stimuli) and the role of the task context, among others.

PMID- 22366727
TI  - Mapping the timecourse of goal-directed attention to location and colour in human
      vision.
AB  - Goal-directed attention prioritises perception of task-relevant stimuli according
      to location, features, or onset time. In this study we compared the behavioural
      timecourse of goal-directed selection to locations and colours by varying the
      stimulus-onset asynchrony (SOA) between cue and target in a strategic cueing
      paradigm. Participants reported the presence or absence of a target following
      prior information regarding its location or colour. Results revealed that
      preparatory selection by colour is more effective at enhancing perceptual
      sensitivity than selection by location, even though both types of cue provided
      equivalent overall information. More detailed analysis revealed that this
      advantage arose due a limitation of spatial attention in maintaining a
      sufficiently broad focus (>2 degrees ) for target detection across multiple
      stimuli. In contrast, when target stimuli fell within 2 degrees  of the spatial
      attention spotlight, the strategic advantages and speed of spatial and colour
      attention were equated. Our findings are consistent with the conclusion that,
      under spatially optimal conditions, prior spatial and colour information are
      equally proficient at guiding top-down selection. When spatial locations are
      ambiguous, however, colour-based selection is the more efficient mechanism.

PMID- 22366728
TI  - A thumb opposition splint to improve manual dexterity and upper-limb functioning
      in Charcot-Marie-Tooth disease.
AB  - OBJECTIVE: To assess initial efficacy and tolerability of a thumb opposition
      splint on manual dexterity, perceived upper limb functioning and occupational
      performance in patients with Charcot-Marie-Tooth disease. DESIGN: One group pre
      post design. PATIENTS AND METHODS: Thirteen patients were provided with a
      neoprene opposition splint for their dominant hand. Manual dexterity (Sollerman
      hand function test), perceived upper limb functioning (Michigan Hand Outcomes
      Questionnaire) and occupational performance (Canadian Occupational Performance
      Measure) were assessed after using the splint and compared with pre-treatment
      scores (paired t-tests). Usability and tolerability were assessed with a
      questionnaire. RESULTS: Sollerman test scores improved significantly from a mean
      of 47 (standard deviation (SD) 11) to 52 (SD 12) points (norm 80 points) (p =
      0.006). Perceived functioning in the domain activities of daily living (scale 0
      100) improved significantly from 51 (SD 20) to 60 (SD 17) points (p = 0.04). Both
      occupational performance and satisfaction scores improved significantly (p =
      0.020). Efficacy did not relate to age, disease duration or severity. Subjects
      were satisfied with splint cosmesis and comfort. CONCLUSION: These results
      indicate that a thumb opposition splint can be applied effectively to improve
      upper limb functioning in patients with Charcot-Marie-Tooth disease.

PMID- 22366729
TI  - Highly selective red- and green-emitting two-photon fluorescent probes for
      cysteine detection and their bio-imaging in living cells.
AB  - Two highly selective two-photon fluorescent probes for cysteine over
      homocysteine, N-acetyl-L-cysteine, dithiothreitol, glutathione and other amino
      acids, and their fluorescent imaging in living cells have been shown.

PMID- 22366730
TI  - Flowing cell trail to determine erythrocyte velocity in rat mesentery
      microcirculation by a consumer grade high-speed camera.

PMID- 22366732
TI  - Substitution saturation and nuclear paralogs of commonly employed phylogenetic
      markers in the Caryophyllidea, an unusual group of non-segmented tapeworms
      (Platyhelminthes).
AB  - Caryophyllidean cestodes (Platyhelminthes) represent an unusual group of
      tapeworms lacking serially repeated body parts that potentially diverged from the
      common ancestor of the Eucestoda prior to the evolution of segmentation. Here we
      evaluate the utility of two nuclear and two mitochondrial molecular markers
      (ssrDNA and lsrDNA, nad3 and cox1) for use in circumscribing generic boundaries
      and estimating interrelationships in the group. We show that these commonly
      employed markers do not contain sufficient signal to infer well-supported
      phylogenetic estimates due to substitution saturation. Moreover, we detected
      multiple trnK+nad3+trnS+trnW+cox1 haplotypes within individuals, indicating a
      history of gene exchange between the mitochondrial and nuclear genomes. The
      presence of such nuclear paralogs (i.e. numts), to our knowledge described here
      in cestodes for the first time, together with the results of phylogenetic,
      saturation and split-decomposition analyses all suggest that finding informative
      markers for estimating caryophyllidean evolution is unusually problematic in
      comparison to other major lineages of tapeworms.

PMID- 22366731
TI  - Ookinete destruction within the mosquito midgut lumen explains Anopheles
      albimanus refractoriness to Plasmodium falciparum (3D7A) oocyst infection.
AB  - Previous studies have shown that the central American mosquito vector, Anopheles
      albimanus, is generally refractory to oocyst infection with allopatric isolates
      of the human malaria parasite Plasmodium falciparum. However, the reasons for the
      refractoriness of A. albimanus to infection with such isolates of P. falciparum
      are unknown. In the current study, we investigated the infectivity of the P.
      falciparum clone 3D7A to laboratory-reared A. albimanus and another natural
      vector of human malaria, Anopheles stephensi. Plasmodium falciparum gametocytes
      grown in vitro were simultaneously fed to both mosquito species and the progress
      of malaria infection compared. In 22 independent paired experimental feeds, no
      mature oocysts were observed on the midguts of A. albimanus 10days after
      bloodfeeding. In contrast, high levels of oocyst infection were found on the
      midguts of simultaneously fed A. stephensi. Direct immunofluorescence microscopy
      and light microscopical examination of Giemsa-stained histological sections were
      used to identify when the P. falciparum clone 3D7A failed to establish mature
      oocyst infections in A. albimanus. Similar densities of macrogametes/zygotes, and
      immature retort-form and mature ookinetes were found within the bloodmeals of
      both mosquito species. However, in A. albimanus, ookinetes were seldom associated
      with the peritrophic matrix, and were neither observed in the ectoperitrophic
      space nor the midgut epithelium. In contrast, ookinetes were frequently observed
      in these midgut compartments in A. stephensi. Additionally, young oocysts were
      observed on the midguts of A. stephensi but not A. albimanus 2days after
      bloodfeeding. Vital staining of the immature retort-form and mature ookinetes
      found within the luminal bloodmeal, demonstrated that a significantly greater
      proportion of these malaria parasite stages were non-viable in A. albimanus
      compared with A. stephensi. Overall, our observations indicate that ookinetes of
      the P. falciparum clone 3D7A are destroyed within the bloodmeal of A. albimanus
      and that the midgut lumen, rather than the midgut epithelium, is the site of
      mosquito refractoriness in this particular malaria parasite-mosquito vector
      combination.

PMID- 22366733
TI  - Epidemiology of mixed Schistosoma mansoni and Schistosoma haematobium infections
      in northern Senegal.
AB  - Due to the large overlap of Schistosoma mansoni- and Schistosoma haematobium
      endemic regions in Africa, many people are at risk of co-infection, with
      potential adverse effects on schistosomiasis morbidity and control. Nonetheless,
      studies on the distribution and determinants of mixed Schistosoma infections have
      to date been rare. We conducted a cross-sectional survey in two communities in
      northern Senegal (n=857) to obtain further insight into the epidemiology of mixed
      infections and ectopic egg elimination. Overall prevalences of S. mansoni and S.
      haematobium infection were 61% and 50%, respectively, in these communities. Among
      infected subjects, 53% had mixed infections and 8% demonstrated ectopic egg
      elimination. Risk factors for mixed infection - i.e. gender, community of
      residence and age - were not different from what is generally seen in Schistosoma
      endemic areas. Similar to overall S. mansoni and S. haematobium infections, age
      related patterns of mixed infections showed the characteristic convex-shaped
      curve for schistosomiasis, with a rapid increase in children, a peak in
      adolescents and a decline in adults. Looking at the data in more detail however,
      the decline in overall S. haematobium infection prevalences and intensities
      appeared to be steeper than for S. mansoni, resulting in a decrease in mixed
      infections and a relative increase in single S. mansoni infections with age.
      Moreover, individuals with mixed infections had higher infection intensities of
      both S. mansoni and S. haematobium than those with single infections, especially
      those with ectopic egg elimination (P<0.05). High infection intensities in mixed
      infections, as well as age-related differences in infection patterns between S.
      mansoni and S. haematobium, may influence disease epidemiology and control
      considerably, and merit further studies into the underlying mechanisms of
      Schistosoma infections in co-endemic areas.

PMID- 22366734
TI  - Tooth hard tissue stimulates bone remodeling as a potential motive force during
      tooth eruption.
AB  - Tooth eruption is an orientating action which migrates teeth coronally during
      life, even in bone or after occlusion contact is lost. The eruption pathway is
      due to bone resorption near the enamel crown and bone deposition around the
      cementum-covered roots. Due to their proximity to bone resorption and deposition,
      we hypothesize that the hard tissues enamel, dentine or cementum are important
      during eruption. In the present study, extracted human teeth were cut into enamel
      samples, enamel-dentine samples or dentine-cementum samples, and implanted into
      bone defects in rabbit tibia. Hematoxylin and eosin, tartrate-resistant acid
      phosphatase activity, tetracycline tracing and scanning electron microscopy were
      used to investigate bone resorption and deposition 1-8 weeks after surgery. The
      results showed that resorption lacunae with numerous osteoclasts were observed
      facing enamel and significant new bone deposition occurred near the cementum
      surface, compared to other hard tooth surfaces. These findings indicate that the
      enamel crown may stimulate bone resorption and initiate the eruption pathway, and
      that the cementum root may stimulate bone deposition. Bone regeneration initiated
      by tooth hard tissues may be a potential motive force during tooth eruption.

PMID- 22366735
TI  - Involvement of mitogen-activated protein kinases and peroxisome proliferator
      activated receptor gamma in monosodium urate crystal-induced vascular cell
      adhesion molecule 1 expression in human rheumatoid arthritis synovial
      fibroblasts.
AB  - To investigate whether monosodium urate (MSU) crystals could induce the
      production of VCAM-1 (vascular cell adhesion molecule 1) in human synovial cells
      and its possible signaling pathways, human synovial cells isolated from synovial
      tissue explants were stimulated with various doses of MSU crystals for different
      time intervals. Expression of VCAM-1 was evaluated with Western blotting. To
      explore the underlying mechanisms, VCAM-1 protein expression was also evaluated
      after activation of several signaling molecules including mitogen-activated
      protein kinases (MAPKs) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) were blocked. Exposure of synovial cells to MSU crystals induced VCAM
      1 expression in culture medium in a dose- and time-dependent manner, reaching a
      plateau at 1000 uM and 24 h. Inhibition of the activation of MAPKs and PPARgamma
      could block this increase. The present results demonstrated that MSU crystals
      could induce VCAM-1 expression. MAPKs and PPARgamma signaling pathways regulated
      the induced VCAM-1 expression.

PMID- 22366736
TI  - Advanced imaging of skeletal manifestations of systemic mastocytosis.
AB  - Systemic mastocytosis comprises a group of clonal disorders of the mast cell that
      most commonly involves the skeletal system. Imaging can be helpful in the
      detection and characterization of the osseous manifestations of this disease.
      While radiography and bone scans are frequently used for this assessment, low
      dose multidetector computed tomography and magnetic resonance imaging can be more
      sensitive for the detection of marrow involvement and for the demonstration of
      the various disease patterns. In this article, we review the pathophysiological
      and clinical features of systemic mastocytosis, discuss the role of imaging for
      staging and management, and illustrate the various cross-sectional imaging
      appearances. Awareness and knowledge of the imaging features of this disorder
      will increase the accuracy of image interpretation and can contribute important
      information for management decisions.

PMID- 22366737
TI  - Non-traumatic anterior cruciate ligament abnormalities and their relationship to
      osteoarthritis using morphological grading and cartilage T2 relaxation times:
      data from the Osteoarthritis Initiative (OAI).
AB  - OBJECTIVES: The aim of this work was to study anterior cruciate ligament (ACL)
      degeneration in relation to MRI-based morphological knee abnormalities and
      cartilage T2 relaxation times in subjects with symptomatic osteoarthritis.
      METHODS: Two radiologists screened the right knee MRI of 304 randomly selected
      participants in the Osteoarthritis Initiative cohort with symptomatic OA, for ACL
      abnormalities. Of the 52 knees with abnormalities, 28 had mucoid degeneration, 12
      had partially torn ACLs, and 12 had completely torn ACLs. Fifty-three randomly
      selected subjects with normal ACLs served as controls. Morphological knee
      abnormalities were graded using the WORMS score. Cartilage was segmented and
      compartment-specific T2 values were calculated. RESULTS: Compared to normal ACL
      knees, those with ACL abnormalities had a greater prevalence of, and more severe,
      cartilage, meniscal, bone marrow, subchondral cyst, and medial collateral
      ligament lesions (all p < 0.05). T2 measurements did not significantly differ by
      ACL status. CONCLUSIONS: ACL abnormalities were associated with more severe
      degenerative changes, likely because of greater joint instability. T2
      measurements may not be well suited to assess advanced cartilage degeneration.

PMID- 22366738
TI  - Diversity of tailed phages in Baltic Sea sediment: large number of siphoviruses
      with extremely long tails.
AB  - We present the first attempt at quantitative analysis of morphological diversity
      of tailed viruses obtained from marine sediments without ultracentrifugation or
      enrichment on specific host strains. Sandy mud samples were collected in the Gulf
      of Gdansk in the spring, autumn and winter. VLPs were analyzed by transmission
      electron microscopy. The distribution of three groups of tailed phages was
      similar in all seasons (Siphoviridae: 52% on average; Myoviridae: 42%;
      Podoviridae: 6%). 19% of siphoviruses had prolate heads. Interestingly, 11% of
      siphoviral particles had tails longer than 300 nm, and 6% longer than 600 nm.

PMID- 22366739
TI  - Simultaneous ingestion of dietary proteins reduces the bioavailability of
      galloylated catechins from green tea in humans.
AB  - PURPOSE: To investigate the influence of dietary proteins (casein, soy protein)
      and skimmed milk on the plasma kinetics of green tea (GT) catechins. METHODS: In
      a randomized cross-over design with one-week intervals, 24 healthy normal-weight
      women consumed a test drink containing 1.75 g GT extract with or without the
      addition of different proteins. Treatments were GT (control), GT with skimmed
      milk (GT + M), GT with caseinate (GT + CS), or GT with soy protein (GT + S).
      Venous blood samples were taken before and several times during a period of 4.5 h
      after consumption of the test drink. Plasma concentrations of catechins were
      analyzed by HPLC with electrochemical detection. RESULTS: Compared to control,
      consumption of GT with milk, caseinate, or soy protein significantly reduced the
      bioavailability (mean area under the plasma concentration-time curve) of total
      catechins (means +/- SEM; GT + M, 87 +/- 5%; GT + CS, 79 +/- 5%; GT + S, 88 +/-
      4%), epigallocatechin gallate (GT + M, 68 +/- 4%; GT + CS, 63 +/- 5%; GT + S, 76
      +/- 5%), and epicatechin gallate (GT + M, 68 +/- 5%; GT + CS, 66 +/- 6%; GT + S,
      77 +/- 6%), while the bioavailability of non-galloylated catechins such as
      epigallocatechin (GT + M, 134 +/- 9%; GT + CS, 118 +/- 9 %; GT + S, 123 +/- 8%)
      and epicatechin (GT + M, 125 +/- 10%; GT + CS, 114 +/- 11%; GT + S, 110 +/- 8%)
      significantly increased. No significant differences in bioavailability of GT
      catechins were observed between the treatments GT + M, GT + CS, or GT + S.
      CONCLUSION: Simultaneous ingestion of dietary proteins reduces the
      bioavailability of galloylated catechins from GT in humans.

PMID- 22366742
TI  - Occipitoatlantal dislocation in an infant: fusion techniques.

PMID- 22366740
TI  - Does equol production determine soy endocrine effects?
AB  - Isoflavones, a group of phytoestrogens, are selective oestrogen receptor (ER)
      modulators. They may positively impact endocrine-related conditions but the
      current evidence is sparse. Equol, a non-steroidal oestrogen, is produced by the
      metabolism of the isoflavone daidzein by intestinal bacteria. In Western
      countries, 30-50% of individuals metabolize daidzein into equol and are known as
      equol producers. Equol production may be the source of benefit from isoflavones
      in endocrine disease.

PMID- 22366743
TI  - Atlantoaxial arthrodesis with autograft versus allograft.

PMID- 22366744
TI  - Acute traumatic subdural hematoma outcome in patients older than 65 years.

PMID- 22366745
TI  - My aching back.

PMID- 22366746
TI  - Typical versus atypical trigeminal neuralgia and other factors that may affect
      results of neurosurgical treatment.

PMID- 22366747
TI  - Cysticercosis treatment: a complex interaction drug-parasite-host.

PMID- 22366748
TI  - The asymptomatic degenerative cervical disc: a dilemma.

PMID- 22366749
TI  - Trigeminal neuralgia: radiosurgery before microvascular decompression.

PMID- 22366750
TI  - Presurgical evaluation of retroauricular subcutaneous tissue thickness in BAHA
      surgery.
AB  - OBJECTIVE: A growing population of implanted patients benefit from the Bone
      Anchored Hearing Aid (BAHA). An important step in the surgery is subcutaneous
      tissue reduction. The proper preparation of the implant site depends on relevant
      tissue removal, which is combined with incision, surgical technique, and
      preliminary retroauricular tissue thickness. STUDY DESIGN: Prospective analysis.
      SETTING: Authors attempt to measure the retroauricular subcutaneous tissue
      thickness and try to trace the correlation between retroauricular subcutaneous
      tissue thickness with objective parameters such as sex, height, weight, and age.
      PATIENTS: Group of hundred randomly selected patients were enrolled in the study.
      INTERVENTION(S): Standard ultrasound with liner transducer probe was applied to
      measure the tissue thickness. MAIN OUTCOME MEASURES: Sex, weight, height, and age
      were correlated with retroauricular tissue thickness; results also were
      calculated for body mass index. RESULTS: The retroauricular subcutaneous tissue
      thickness ranged between 2.0 and 11.0 mm with the mean value of 5.25 mm.
      Statistical validation revealed strong correlation with weight and body mass
      index. Statistical difference was found between retroauricular subcutaneous
      tissue thickness and sex, confirming women to have thinner subcutaneous tissue
      than men. The age of the patient also was predictive but without the linear
      correlation. Conducted measurements revealed no association between
      retroauricular subcutaneous tissue thickness and height of the patients enrolled
      in the study. CONCLUSION: Our results provide a predictive value during
      preoperative counseling of patients and planning the surgery. Basic information
      obtained during the examination can help choose the optimal implantation
      technique. The ultrasound examination applied in the study turned to be an easy
      and reliable method to assess the retroauricular tissue thickness before the
      surgery.

PMID- 22366751
TI  - Assessment of postural stability using foam posturography at the chronic stage
      after acute unilateral peripheral vestibular dysfunction.
AB  - OBJECTIVE: To investigate the utility of foam posturography for assessing
      equilibrium at the chronic stage after acute unilateral peripheral
      vestibulopathy. METHODS: Thirty-four consecutive patients (16 patients at the
      chronic stage) with acute unilateral peripheral vestibulopathy and absent caloric
      responses unilaterally were recruited, along with 66 healthy control subjects.
      Two-legged stance tasks were performed in 4 conditions: with eyes open or closed,
      with or without using foam rubber. We adopted 6 parameters: the movement velocity
      of the center of pressure, the envelopment area traced by the movement of the
      center of pressure with eyes closed/foam rubber, Romberg's ratios of velocity and
      area with foam rubber, and the foam ratios (the ratio of a parameter measured
      with and without foam rubber) of velocity and area with eyes closed. RESULTS: All
      6 parameters were significantly higher in the patients in the acute/subacute
      stage (<3 mo) than in the control subjects (p < 0.0001). Five parameters,
      excluding the foam ratio of the area with eyes closed, were still significantly
      higher in the patients at the chronic stage (>3 mo) than in the control subjects
      (p < 0.01). CONCLUSION: Foam posturography is useful for assessing equilibrium
      even at the chronic stage after acute unilateral peripheral vestibulopathy.

PMID- 22366752
TI  - Application of active middle ear implants in patients with severe mixed hearing
      loss.
AB  - OBJECTIVE: To determine the long-term benefit of the Vibrant Soundbridge (VSB)
      middle ear implant in patients with severe mixed hearing loss and to compare it
      with other hearing devices. DESIGN: A retrospective analysis. SETTING: University
      affiliated medical center. PATIENTS: Six patients with severe mixed hearing loss
      and a mean sensorineural hearing loss component between 40 and 70 dB.
      INTERVENTIONS: Patients received a VSB with the floating mass transducer (FMT)
      coupled to the round window or to the oval window via a residual stapes
      structure. MAIN OUTCOME MEASURES: Functional gain and speech recognition results.
      Results are compared with 2 control groups matched for mean sensorineural hearing
      loss: 1) patients with mixed hearing loss and a bone-anchored hearing device, and
      2) patients with sensorineural hearing loss and traditional implantation of the
      VSB. RESULTS: There is large variance in functional gain between the patients
      suggesting high variability in the effectivity of the FMT coupling. The speech
      recognition results for the experimental group were not systematically better
      than in either control group. CONCLUSION: There is large variability in results
      that might be ascribed to coupling effectivity. On the average, speech
      recognition results were not better or worse than those found in patients with
      similar hearing loss fitted with bone-anchored hearing devices.

PMID- 22366753
TI  - Laser Eustachian tuboplasty: efficiency evaluation in the pressure chamber.
AB  - OBJECTIVE: Laser Eustachian tuboplasty (LETP) with ablation of the epipharyngeal
      orifice of the Eustachian tube (ET) shows good results in clinical observation.
      However, to this day, there are no reports evaluating the surgical procedure with
      valid test methods. The purpose of this study was to test the effect of minimally
      invasive LETP by means of a pressure chamber ET function test. STUDY DESIGN:
      Prospective surgical trial. SETTING: Tertiary and university hospital. PATIENTS:
      Thirty patients with a history of ET dysfunction during pressure changes were
      examined. INTERVENTION: Minimally invasive LETP was performed with an 812-nm
      diode laser under local anesthesia as an outpatient procedure. MAIN OUTCOME
      MEASURE: The ET function was tested preoperatively and postoperatively by
      pressure chamber ET function test. Eustachian tube closing pressure (ETCP) was
      evaluated as a measure of the tissue pressure of the ET. In cases of a severely
      impaired ET function, a "blocked" pattern was evident, and no measurement of ETCP
      was possible. RESULTS: Before minimally invasive LETP, 17 patients showed a
      completely blocked pattern. Postoperatively, 13 patients of this group showed an
      improved ET function with a restored normal opening pattern (p < 0.001). The ETCP
      was reduced from 6.24 +/- 3.46 mbar preoperatively to 4.06 +/- 2.36 mbar
      postoperatively (p < 0.013). CONCLUSION: The results strongly indicate that the
      effect of minimally invasive LETP can be proven by measuring the ET function in a
      pressure chamber. Results must be interpreted in combination with clinical
      methods like Valsalva maneuver and tympanometry. Patients with ET dysfunction
      during pressure changes seem to benefit from the minimally invasive LETP.

PMID- 22366754
TI  - Facile synthesis of 4-substituted 3,4-dihydrocoumarins via an organocatalytic
      double decarboxylation process.
AB  - 3,4-Dihydrocoumarins, considered to be valuable building blocks, have attracted
      considerable attention due to their various biological activities. Herein, we
      have documented an efficient and convenient double decarboxylation process for
      the synthesis of 4-substituted 3,4-dihydrocoumarin in moderate to excellent
      yields under mild reaction conditions (up to 98%).

PMID- 22366755
TI  - [Frontotemporal dementias].
AB  - Frontotemporal dementias (FTD) account for only 5-7% of all dementia aetiologies.
      However, FTD is one common form of dementia in the presenile period with a
      symptom onset between an age of 45 and 65 years. FTD are clinically classified
      into a group of rare genetic variants, the behavioural variant, primary
      progressive aphasias and a variant including motor neuron symptoms (FTD-MNS). In
      recent years the pathobiological characteristics of some FTD variants was
      clarified, demonstrating a pathological accumulation of TAR-DNA binding protein
      43 (TDP-43) as a common pathological substrate. The revised diagnostic criteria
      of the behavioural variant of the FTD require at least three of six clinically
      discriminating features (disinhibition, apathy, loss of sympathy, perseverative
      behaviours, hyperorality and dysexecutive neuropsychological profile). The
      primary progressive aphasias are classified in a nonfluent/agrammatic variant, a
      logopenic variant and a semantic variant according to clinical and imaging
      features. Movement disorders and more precisely a Parkinsonian syndrome can be
      part of the FTD spectrum. Some clinical features overlap the clinical diagnosis
      of a progressive supranuclear paralysis and the corticobasal ganglionic
      degeneration. A causal therapy does not exist and medical treatment is directed
      at the patient's key symptoms. Different agents such as serotonin reuptake
      inhibitors, tricyclic antidepressants, atypical neuroleptics, carbamazepine,
      valproate, lamotrigine and when indicated also acetylcholinesterase inhibitors
      are potentially helpful. All together, theses medical treatments have a low level
      of evidence. Non-pharmacological therapies such as physiotherapy, occupational
      therapy, speech therapy and disease-specific education of the patient and their
      relatives are important to ensure a safe residential environment and daily
      routine.

PMID- 22366756
TI  - Slow oscillations in two pairs of dopaminergic neurons gate long-term memory
      formation in Drosophila.
AB  - A fundamental duty of any efficient memory system is to prevent long-lasting
      storage of poorly relevant information. However, little is known about dedicated
      mechanisms that appropriately trigger production of long-term memory (LTM). We
      examined the role of Drosophila dopaminergic neurons in the control of LTM
      formation and found that they act as a switch between two exclusive consolidation
      pathways leading to LTM or anesthesia-resistant memory (ARM). Blockade, after
      aversive olfactory conditioning, of three pairs of dopaminergic neurons
      projecting on mushroom bodies, the olfactory memory center, enhanced ARM, whereas
      their overactivation conversely impaired ARM. Notably, blockade of these neurons
      during the intertrial intervals of a spaced training precluded LTM formation. Two
      pairs of these dopaminergic neurons displayed sustained calcium oscillations in
      naive flies. Oscillations were weakened by ARM-inducing massed training and were
      enhanced during LTM formation. Our results indicate that oscillations of two
      pairs of dopaminergic neurons control ARM levels and gate LTM.

PMID- 22366757
TI  - Serotonergic transcriptional networks and potential importance to mental health.
AB  - Transcription regulatory networks governing the genesis, maturation and
      maintenance of vertebrate brain serotonin (5-HT) neurons determine the level of
      serotonergic gene expression and signaling throughout an animal's lifespan.
      Recent studies suggest that alterations in these networks can cause behavioral
      and physiological pathogenesis in mice. Here, we synthesize findings from
      vertebrate loss-of-function and gain-of-function studies to build a new model of
      the transcriptional regulatory networks that specify 5-HT neurons during fetal
      life, integrate them into CNS circuitry in early postnatal life and maintain them
      in adulthood. We then describe findings from animal and human genetic studies
      that support possible alterations in the activity of serotonergic regulatory
      networks in the etiology of mental illness. We conclude with a discussion of the
      potential utility of our model, as an experimentally well-defined molecular
      pathway, to predict and interpret the biological effect of genetic variation that
      may be discovered in the orthologous human network.

PMID- 22366758
TI  - N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death.
AB  - Transient global ischemia in rats induces delayed death of hippocampal CA1
      neurons. Early events include caspase activation, cleavage of anti-death Bcl-2
      family proteins and large mitochondrial channel activity. However, whether these
      events have a causal role in ischemia-induced neuronal death is unclear. We found
      that the Bcl-2 and Bcl-x(L) inhibitor ABT-737, which enhances death of tumor
      cells, protected rats against neuronal death in a clinically relevant model of
      brain ischemia. Bcl-x(L) is prominently expressed in adult neurons and can be
      cleaved by caspases to generate a pro-death fragment, DeltaN-Bcl-x(L). We found
      that ABT-737 administered before or after ischemia inhibited DeltaN-Bcl-x(L)
      induced mitochondrial channel activity and neuronal death. To establish a causal
      role for DeltaN-Bcl-x(L), we generated knock-in mice expressing a caspase
      resistant form of Bcl-x(L). The knock-in mice exhibited markedly reduced
      mitochondrial channel activity and reduced vulnerability to ischemia-induced
      neuronal death. These findings suggest that truncated Bcl-x(L) could be a
      potentially important therapeutic target in ischemic brain injury.

PMID- 22366759
TI  - Primary oligodendrocyte death does not elicit anti-CNS immunity.
AB  - Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the
      initial trigger of this autoreactivity remains elusive. One of the proposed
      factors for initiating this disease is the primary death of oligodendrocytes. To
      specifically test such oligodendrocyte death as a trigger for anti-CNS immunity,
      we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia
      macrophage activation followed oligodendrocyte death, and myelin components in
      draining lymph nodes made CNS antigens available to lymphocytes. However, even
      conditions favoring autoimmunity-bystander activation, removal of regulatory T
      cells, presence of myelin-reactive T cells and application of demyelinating
      antibodies-did not result in the development of CNS inflammation after
      oligodendrocyte death. In addition, this lack of reactivity was not mediated by
      enhanced myelin-specific tolerance. Thus, in contrast with previously reported
      impairments of oligodendrocyte physiology, diffuse oligodendrocyte death alone or
      in conjunction with immune activation does not trigger anti-CNS immunity.

PMID- 22366760
TI  - Unique functional properties of somatostatin-expressing GABAergic neurons in
      mouse barrel cortex.
AB  - Neocortical GABAergic neurons have diverse molecular, structural and
      electrophysiological features, but the functional correlates of this diversity
      are largely unknown. We found unique membrane potential dynamics of somatostatin
      expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex
      of awake behaving mice. SOM neurons were spontaneously active during periods of
      quiet wakefulness. However, SOM neurons hyperpolarized and reduced action
      potential firing in response to both passive and active whisker sensing, in
      contrast with all other recorded types of nearby neurons, which were excited by
      sensory input. Optogenetic inhibition of SOM neurons increased burst firing in
      nearby excitatory neurons. We hypothesize that the spontaneous activity of SOM
      neurons during quiet wakefulness provides a tonic inhibition to the distal
      dendrites of excitatory pyramidal neurons. Conversely, the inhibition of SOM
      cells during active cortical processing likely enhances distal dendritic
      excitability, which may be important for top-down computations and sensorimotor
      integration.

PMID- 22366761
TI  - Temporal variability in the deglutition literature.
AB  - A literature review was conducted on temporal measures of swallowing in healthy
      individuals with the purpose of determining the degree of variability present in
      such measures within the literature. A total of 46 studies that met inclusion
      criteria were reviewed. The definitions and descriptive statistics for all
      reported temporal parameters were compiled for meta-analysis. In total, 119
      different temporal parameters were found in the literature. The three most
      frequently occurring durational measures were upper esophageal sphincter opening,
      laryngeal closure, and hyoid movement. The three most-frequently occurring
      interval measures were stage transition duration, pharyngeal transit time, and
      duration from laryngeal closure-to-UES opening. Subtle variations in operational
      definitions across studies were noted, making the comparison of data challenging.
      Analysis of forest plots compiling descriptive statistical data (means and 95%
      confidence intervals) across studies revealed differing degrees of variability
      across durations and intervals. Two parameters (UES opening duration and the
      laryngeal closure-to-UES opening interval) demonstrated the least variability,
      reflected by small ranges for mean values and tight confidence intervals. Trends
      emerged for factors of bolus size and participant age for some variables. Other
      potential sources of variability are discussed.

PMID- 22366762
TI  - Toxic and non-toxic aggregates from the SBMA and normal forms of androgen
      receptor have distinct oligomeric structures.
AB  - Hormone-dependent aggregation of the androgen receptor (AR) with a polyglutamine
      (polyQ) stretch amplification (>38) is considered to be the causative agent of
      the neurodegenerative disorder spinal and bulbar muscular atrophy (SBMA),
      consistent with related neurodegenerative diseases involving polyQ-extended
      proteins. In spite of the widespread acceptance of this common causal hypothesis,
      little attention has been paid to its apparent incompatibility with the
      observation of AR aggregation in healthy individuals with no polyQ stretch
      amplification. Here we used atomic force microscopy (AFM) to characterize sub
      micrometer scale aggregates of the wild-type (22 glutamines) and the SBMA form
      (65 glutamines), as well as a polyQ deletion mutant (1 glutamine) and a variant
      with a normal length polyQ stretch but with a serine to alanine double mutation
      elsewhere in the protein. We used a baculovirus-insect cell expression system to
      produce full-length proteins for these structural analyses. We related the AFM
      findings to cytotoxicity as measured by expression of the receptors in Drosophila
      motoneurons or in neuronal cells in culture. We found that the pathogenic AR
      mutants formed oligomeric fibrils up to 300-600nm in length. These were clearly
      different from annular oligomers 120-180nm in diameter formed by the
      nonpathogenic receptors. We could also show that melatonin, which is known to
      ameliorate the pathological phenotype in the fly model, caused polyQ-extended AR
      to form annular oligomers. Further comparative investigation of these
      reproducibly distinct toxic and non-toxic oligomers could advance our
      understanding of the molecular basis of the polyQ pathologies.

PMID- 22366763
TI  - Disruption of Nrf2/ARE signaling impairs antioxidant mechanisms and promotes cell
      degradation pathways in aged skeletal muscle.
AB  - Age-associated decline in antioxidant potential and accumulation of reactive
      oxygen/nitrogen species are primary causes for multiple health problems,
      including muscular dystrophy and sarcopenia. The role of the nuclear erythroid-2
      p45-related factor-2 (Nrf2) signaling has been implicated in antioxidant gene
      regulation. Here, we investigated the loss-of-function mechanisms for age
      dependent regulation of Nrf2/ARE (Antioxidant Response Element) signaling in
      skeletal muscle (SM). Under basal physiological conditions, disruption of Nrf2
      showed minimal effects on antioxidant defenses in young (2months) Nrf2-/- mice.
      Interestingly, mRNA and protein levels of NADH Quinone Oxidase-1 were
      dramatically (*P<0.001) decreased in Nrf2-/- SM when compared to WT at 2months of
      age, suggesting central regulation of NQO1 occurs through Nrf2. Subsequent
      analysis of the Nrf2-dependent transcription and translation showed that the aged
      mice (>24months) had a significant increase in ROS along with a decrease in
      glutathione (GSH) levels and impaired antioxidants in Nrf2-/- when compared to WT
      SM. Further, disruption of Nrf2 appears to induce oxidative stress (increased
      ROS, HNE-positive proteins), ubiquitination and pro-apoptotic signals in the aged
      SM of Nrf2-/- mice. These results indicate a direct role for Nrf2/ARE signaling
      on impairment of antioxidants, which contribute to muscle degradation pathways
      upon aging. Our findings conclude that though the loss of Nrf2 is not amenable at
      younger age; it could severely affect the SM defenses upon aging. Thus, Nrf2
      signaling might be a potential therapeutic target to protect the SM from age
      dependent accumulation of ROS by rescuing redox homeostasis to prevent age
      related muscle disorders such as sarcopenia and myopathy.

PMID- 22366764
TI  - Peroxisomal ABC transporters: structure, function and role in disease.
AB  - ATP-binding cassette (ABC) transporters belong to one of the largest families of
      membrane proteins, and are present in almost all living organisms from eubacteria
      to mammals. They exist on plasma membranes and intracellular compartments such as
      the mitochondria, peroxisomes, endoplasmic reticulum, Golgi apparatus and
      lysosomes, and mediate the active transport of a wide variety of substrates in a
      variety of different cellular processes. These include the transport of amino
      acids, polysaccharides, peptides, lipids and xenobiotics, including drugs and
      toxins. Three ABC transporters belonging to subfamily D have been identified in
      mammalian peroxisomes. The ABC transporters are half-size and assemble mostly as
      a homodimer after posttranslational transport to peroxisomal membranes.
      ABCD1/ALDP and ABCD2/ALDRP are suggested to be involved in the transport of very
      long chain acyl-CoA with differences in substrate specificity, and ABCD3/PMP70 is
      involved in the transport of long and branched chain acyl-CoA. ABCD1 is known to
      be responsible for X-linked adrenoleukodystrophy (X-ALD), an inborn error of
      peroxisomal beta-oxidation of very long chain fatty acids. Here, we summarize
      recent advances and important points in our advancing understanding of how these
      ABC transporters target and assemble to peroxisomal membranes and perform their
      functions in physiological and pathological processes, including the
      neurodegenerative disease, X-ALD.

PMID- 22366765
TI  - Molecular control of rodent spermatogenesis.
AB  - Spermatogenesis is a complex developmental process that ultimately generates
      mature spermatozoa. This process involves a phase of proliferative expansion,
      meiosis, and cytodifferentiation. Mouse models have been widely used to study
      spermatogenesis and have revealed many genes and molecular mechanisms that are
      crucial in this process. Although meiosis is generally considered as the most
      crucial phase of spermatogenesis, mouse models have shown that pre-meiotic and
      post-meiotic phases are equally important. Using knowledge generated from mouse
      models and in vitro studies, the current review provides an overview of the
      molecular control of rodent spermatogenesis. Finally, we briefly relate this
      knowledge to fertility problems in humans and discuss implications for future
      research. This article is part of a Special Issue entitled: Molecular Genetics of
      Human Reproductive Failure.

PMID- 22366766
TI  - EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in gastric
      cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways.
AB  - 5-Fluorouracil (5-FU) plays an important role in the chemotherapy of advanced
      gastric cancer. However, genetic factors that affect therapeutic efficacy of 5-FU
      warrant further investigation. In the present study, using stable transfection of
      the ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) gene, we explored the
      genetic influences on 5-FU-induced apoptosis of human gastric cancer cells.
      Stable overexpression of the EBP50 gene was determined by reverse transcription
      polymerase chain reaction (RT-PCR) assay and western blot analysis. After
      treatment with 5-FU, cell growth activities in vitro were investigated by MTT
      assay. Cell apoptosis was evaluated by Hoechst 33258 staining and flow cytometry
      of Annexin V-FITC/PI staining. Compared with the BGC823 or BGC823/neo cells,
      EBP50 mRNA and protein levels in the BGC823/EBP50 cells (EBP50-transfected BGC823
      cells) were markedly higher. Chemosensitivity and apoptosis rates of the
      BGC823/EBP50 cells were higher compared to the BGC823 and BGC823/neo cells
      following treatment with 5-FU. Stable overexpression of extrinsic EBP50
      distinctly increases the 5-FU-induced apoptosis of gastric cancer cells, and is a
      novel strategy by which to improve the chemosensitivity of gastric cancer to 5
      FU.

PMID- 22366767
TI  - Optimization of medium formulation and seed conditions for expression of mature
      PsaA (pneumococcal surface adhesin A) in Escherichia coli using a sequential
      experimental design strategy and response surface methodology.
AB  - PsaA, a candidate antigen for a vaccine against pneumonia, is well-conserved in
      all Streptococcus pneumoniae serotypes. A sequence of two-level experimental
      designs was used to evaluate medium composition and seed conditions to optimize
      the expression of soluble mature PsaA in E. coli. A face-centered central
      composite design was first used to evaluate the effects of yeast extract (5 and
      23.6 g/L), tryptone (0 and 10 g/L), and glucose (1 and 10 g/L), with replicate
      experiments at the central point (14.3 g/L yeast extract, 5 g/L tryptone, 5.5 g/L
      glucose). Next, a central composite design was used to analyze the influence of
      NaCl concentration (0, 5, and 10 g/L) compared with potassium salts (9.4 g/L
      K(2)HPO(4)/2.2 g/L KH(2)PO(4)), and seed growth (7 and 16 h). Tryptone had no
      significant effect and was removed from the medium. Yeast extract and glucose
      were optimized at their intermediate concentrations, resulting in an animal
      derived material-free culture medium containing 15 g/L yeast extract, 8 g/L
      glucose, 50 MUg/mL kanamycin, and 0.4% glycerol, yielding 1 g/L rPsaA after 16 h
      induction at 25 degrees C in shake flasks at 200 rpm. All the seed age and salt
      conditions produced similar yields, indicating that no variation had a
      statistically significant effect on expression. Instead of growing the seed
      culture for 16 h (until saturation), the process can be conducted with 7 h seed
      growth until the exponential phase. These results enhanced the process
      productivity and reduced costs, with 5 g/L NaCl being used rather than potassium
      salts.

PMID- 22366769
TI  - Early onset Alzheimer's disease is associated with a distinct neuropsychological
      profile.
AB  - Alzheimer's disease (AD) in younger patients is associated with a higher
      prevalence of atypical symptoms. We examined neuropsychological performance
      according to age-at-onset. We assessed cognition in 172 patients with AD (81
      early and 91 late onset) in five cognitive domains (memory, language, visuo
      spatial functioning, executive functioning, attention). Dementia severity was
      assessed using the Mini-Mental State Examination (MMSE) and global cognitive
      decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were
      performed with age-at-onset as between-subjects factor, and gender and education
      as covariates. Analysis was repeated after stratification for dementia severity
      (based on median MMSE). In early onset AD, age (mean +/- SD) was 60 +/- 4 years;
      44 (54%) were female. In late onset AD, age was 72 +/- 5 years; 47 (52%) were
      female. Dementia severity and global cognitive decline did not differ between
      groups (early onset: MMSE: 20 +/- 5, CAMCOG: 69 +/- 15, late onset: MMSE: 21 +/-
      5, CAMCOG: 70 +/- 15; p > 0.05). Early onset patients performed worse than late
      onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p
      < 0.001), and attention (p < 0.01). Late onset patients performed worse on
      memory, although not significantly (p = 0.11). Stratification for dementia
      severity showed that in mildly demented early onset patients, memory function was
      remarkably preserved compared to late onset patients (p < 0.01). In moderate AD,
      differences in memory function disappeared, but early onset patients performed
      worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001),
      and attention (p < 0.01) than late onset patients. Adjustment for APOE left
      results unchanged. In conclusion, early onset AD presents with a different
      cognitive profile and the disease course seems different. Relative sparing of
      memory function in early stages stresses the need to adequately test other
      cognitive domains.

PMID- 22366770
TI  - Clinical, neuropathological, and genetic characteristics of the novel IVS9+1delG
      GRN mutation in a patient with frontotemporal dementia.
AB  - Frontotemporal lobar degeneration (FTLD) refers to a clinically, pathologically,
      and genetically heterogeneous group of dementias that arises from the
      degeneration of the frontal and temporal lobes. Mutations in the progranulin gene
      (GRN) are a major cause of FTLD with TDP-43 inclusions. Herein, we describe the
      clinical, neuropathological, and genetic findings in a case of autosomal dominant
      behavioral variant of frontotemporal dementia (bvFTD) with asymmetrical
      parkinsonism and prominent visuospatial deficits that carries a novel GRN
      mutation. This case highlights important clinical characteristics that seem to be
      common in FTLD GRN-associated patients, such as asymmetrical parkinsonism and
      parietal symptoms, and that are correlated to the pathological involvement of
      striatum (rather than substantia nigra in our case) and parietal lobe. We also
      emphasize that plasma progranulin level can be useful to infer about the
      pathogenicity of new GRN mutations.

PMID- 22366768
TI  - Use of the Saccharomyces cerevisiae endopolygalacturonase promoter to direct
      expression in Escherichia coli.
AB  - In Saccharomyces cerevisiae, an endopolygalacturonase encoded by the PGL1 gene
      catalyzes the random hydrolysis of the alpha-1,4 glycosidic linkages in
      polygalacturonic acid. To study the regulation of the PGL1 gene, we constructed a
      reporter vector containing the lacZ gene under the control of PGL1 promoter.
      Surprisingly, when Escherichia coli DH5alpha was transformed by this vector,
      cells harboring the constructed plasmid produced blue colonies. Sequence analysis
      of this promoter revealed that E. coli consensus sequences required to express an
      in-frame lacZ alpha product were present. We next decided to investigate how the
      PGL1 promoter is regulated in E. coli compared to yeast. In this study, we
      examined the modulation of the PGL1 promoter in E. coli, and the results
      indicated that its activity is greatly induced by saturated digalacturonic acid
      and is indirectly regulated by the transcriptional regulators the 2-keto-3
      deoxygluconate repressor. Moreover, PGL1 expression is enhanced under aerobic
      conditions. We found that beta-galactosidase activity in E. coli could reach 180
      units, which is 40-fold greater than the activity produced in S. cerevisiae, and
      greater than recombinant protein expression previously reported by other
      researchers. We thus demonstrate that this vector can be considered as a dual
      expression plasmid for both E. coli and S. cerevisiae hosts. So far, no
      modulation of endoPG promoters expressed in E. coli has been reported.

PMID- 22366773
TI  - The role of diet in the pathogenesis and management of irritable bowel syndrome
      (Review).
AB  - Most patients with irritable bowel syndrome (IBS) believe that diet plays a
      significant role in inducing IBS symptoms and desire to know what foods to avoid.
      It has been found that the intake of calories, carbohydrates, proteins and fat by
      IBS patients does not differ from that of the background population. IBS patients
      were found to avoid certain food items that are rich in fermentable oligo-, di-
      and monosacharides and polyols (FODMAPs), but they did have a high consumption of
      many other FODMAP-rich food items. The diet of IBS patients was found to consist
      of a low calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There
      is no consistent evidence that IBS patients suffer from food allergy, nor is
      there documented evidence that food intolerance plays a role in IBS symptoms.
      Abnormalities in gut hormones have been reported in IBS patients. As gut hormones
      control and regulate gastrointestinal motility and sensation, this may explain
      the abnormal gastrointestinal motility and visceral hypersensitivity reported in
      these patients. Guidance concerning food management which includes individually
      based restrictions of FODMAP-rich food items and individual evaluation of the
      effects of protein-, fat- and carbohydrate-rich/poor diets may reduce IBS
      symptoms.

PMID- 22366772
TI  - A critical review of vitamin C for the prevention of age-related cognitive
      decline and Alzheimer's disease.
AB  - Antioxidants in the diet have long been thought to confer some level of
      protection against the oxidative damage that is involved in the pathology of
      Alzheimer's disease as well as general cognitive decline in normal aging.
      Nevertheless, support for this hypothesis in the literature is equivocal. In the
      case of vitamin C (ascorbic acid) in particular, lack of consideration of some of
      the specific features of vitamin C metabolism has led to studies in which
      classification of participants according to vitamin C status is inaccurate, and
      the absence of critical information precludes the drawing of appropriate
      conclusions. Vitamin C levels in plasma are not always reported, and estimated
      daily intake from food diaries may not be accurate or reflect actual plasma
      values. The ability to transport ingested vitamin C from the intestines into
      blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1)
      and thus very high intakes and the use of supplements are often erroneously
      considered to be of greater benefit that they really are. The current review
      documents differences among the studies in terms of vitamin C status of
      participants. Overall, there is a large body of evidence that maintaining healthy
      vitamin C levels can have a protective function against age-related cognitive
      decline and Alzheimer's disease, but avoiding vitamin C deficiency is likely to
      be more beneficial than taking supplements on top of a normal, healthy diet.

PMID- 22366774
TI  - Association between WDR21A polymorphisms and airway responsiveness to inhaled
      corticosteroids in asthmatic patients.
AB  - OBJECTIVE: Genetic polymorphism is partially responsible for the wide variation
      in the response of moderate-to-severe asthmatic patients to inhaled
      corticosteroids. The goal of the study was to examine polymorphisms in WDR21A,
      which encodes a putative glucocorticoid receptor (GR)-interacting protein, for
      their possible association with corticosteroid responsiveness. METHODS: The
      change in forced expiratory volume in 1 s [FEV(1) (DeltaFEV(1))] induced by 4
      weeks of inhaled treatment with fluticasone propionate (1000 ug daily) was
      measured in 230 asthmatic patients. Fifteen single nucleotide polymorphisms
      (SNPs) of WDR21A were genotyped using a TaqMan assay, and 11 SNPs were used for
      further analysis. WDR21A transcripts were analyzed for variant splicing using
      reverse transcriptase-PCR. The WDR21A protein structure was predicted using a
      template-based modeling method and docked to a GR using Zdock. RESULTS: Of the 11
      SNPs and three haplotypes of WDR21A analyzed, only the intronic SNP -10073G>C
      appeared to affect DeltaFEV(1). The DeltaFEV(1) of the -10073C/C homozygous
      genotype was twice that of the -10073G/G and -10073C/G genotypes (P(corr)=0.04 in
      recessive model). No splicing variant of WDR21A was observed, regardless of
      genotype. The predicted WDR21A protein structure was similar to the Gbeta(1)
      protein structure (template modeling-score=0.93). CONCLUSION: The minor allele 
      10073C of WDR21A may induce a good response to inhaled corticosteroids possibly
      through competition with the Gbeta(1) proteins for binding to GRs.

PMID- 22366776
TI  - Inflation in the number of eligibility criteria for industry-sponsored phase II
      cancer clinical trial: illustration over a 20-year period.

PMID- 22366775
TI  - Impaired associative taste learning and abnormal brain activation in kinase
      defective eEF2K mice.
AB  - Memory consolidation is defined temporally based on pharmacological interventions
      such as inhibitors of mRNA translation (molecular consolidation) or post
      acquisition deactivation of specific brain regions (systems level consolidation).
      However, the relationship between molecular and systems consolidation are poorly
      understood. Molecular consolidation mechanisms involved in translation initiation
      and elongation have previously been studied in the cortex using taste-learning
      paradigms. For example, the levels of phosphorylation of eukaryotic elongation
      factor 2 (eEF2) were found to be correlated with taste learning in the gustatory
      cortex (GC), minutes following learning. In order to isolate the role of the eEF2
      phosphorylation state at Thr-56 in both molecular and system consolidation, we
      analyzed cortical-dependent taste learning in eEF2K (the only known kinase for
      eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal
      levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical
      dependent associative, but not of incidental, taste learning. In order to gain a
      better understanding of the underlying mechanisms, we compared brain activity as
      measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K
      ki mice and WT mice during conditioned taste aversion (CTA) learning and observed
      clear differences between the two but saw no differences under basal conditions.
      Our results demonstrate that adequate levels of phosphorylation of eEF2 are
      essential for cortical-dependent associative learning and suggest that
      malfunction of memory processing at the systems level underlies this associative
      memory impairment.

PMID- 22366777
TI  - Conservative handling of missing data.

PMID- 22366778
TI  - Notes on testing non-inferiority under the partial verification design with a
      confirmatory procedure limited to screen positives.
AB  - When a new test with fewer invasions or less expenses to administer than the
      traditional test is developed, we may be interested in testing whether the former
      is non-inferior to the latter with respect to test accuracy. We define non
      inferiority via both the odds ratio (OR) of correctly identifying a case and the
      OR of correctly identifying a non-case between two tests under comparison. We
      focus our discussion on testing the non-inferiority of a new screening test to a
      traditional screening test when a confirmatory procedure is performed only on
      patients with screen positives. On the basis of well-established methods for
      paired-sample data, we derive an asymptotic test procedure and an exact test
      procedure with respect to the two ORs defined here. Using Monte Carlo simulation,
      we evaluate the performance of these test procedures in a variety of situations.
      We note that the test procedures proposed here can also be applicable if we are
      interested in testing non-inferiority with respect to the ratio of sensitivities
      and the ratio of specificities. We discuss interval estimation of these ORs and
      sample size calculation based on the asymptotic test procedure considered here.
      We use the data taken from a study of the prostate-specific-antigen (PSA) test
      and the digital rectal examination (DRE) test to illustrate the practical use of
      these test procedures, interval estimators and sample size calculation formula.

PMID- 22366771
TI  - The 2008-2012 French Alzheimer plan: description of the national Alzheimer
      information system.
AB  - In France, one of the aims of the current national Alzheimer's disease plan is to
      collect data from all memory centers (memory units, memory resource and research
      centers, independent neurologists) throughout the country. Here we describe the
      French Alzheimer Information System and present a 'snapshot' of the data
      collected throughout the country during the first year of operation. We analyzed
      all data transmitted by memory centers between January 2010 and December 2010.
      Each participating center is required to transmit information on patients to the
      French National Alzheimer dataBank (BNA). This involves completing a computer
      file containing 31 variables corresponding to a limited data set on AD (CIMA:
      Corpus minimum d'information Alzheimer). In 2010, the BNA received data from 320
      memory centers relating to 199,113 consultations involving 118,776 patients. An
      analysis of the data shows that the initial MMSE (Mini Mental State Examination)
      mean score for patients in France was 16.8 points for Alzheimer's disease, 25.7
      points for mild cognitive impairment, and 18.8 points for 'related disorders
      related disorders. The BNA will provide longitudinal data that can be used to
      assess the needs of individual local health areas and size specialized care
      provision in each regional health scheme. By contributing to the BNA, the memory
      centers enhance their clinical activity and help to advance knowledge in
      epidemiology and medical research in the important field of Alzheimer's disease
      and related dementias.

PMID- 22366780
TI  - Facile air-oxidation of large aromatic hydrocarbon bay regions to bay region
      quinones: predicted oxygen-sensitivity of hydrogen-terminated carbon nanotubes.
AB  - Dimesitylbisanthene (1) oxidizes to the corresponding bay region quinone (2) on
      standing in solutions exposed to air and ambient light. It is anticipated that
      hydrogen-terminated carbon nanotubes with bay regions on the rim are likely to
      exhibit even greater sensitivity toward air oxidation.

PMID- 22366782
TI  - Activity limitations before and after surgical carpal tunnel release among
      patients with and without diabetes.
AB  - OBJECTIVES: To evaluate activity limitations before and after carpal tunnel
      release among patients with and without diabetes, to explore differences between
      genders and the influence of grip strength on activity limitations. DESIGN:
      Prospective case-control study. PATIENTS: Thirty-three patients with diabetes and
      carpal tunnel syndrome (CTS) were age and gender matched with 30 patients without
      diabetes having idiopathic CTS. METHODS: Activity limitations were assessed pre
      operatively, 3 and 12 months after surgery, with the self-administered Evaluation
      of Daily Activities Questionnaire (EDAQ) containing 102 activity items in 11
      dimensions and 3 additional male-activity-oriented dimensions including 22 items.
      RESULTS: For all dimensions the mean score was higher for patients with diabetes
      compared with patients without diabetes. This indicates a more pronounced
      activity limitation for patients with diabetes. However, no statistical
      differences between the two groups could be demonstrated. In general, females
      have significantly higher activity limitation scores than males. CONCLUSION: CTS
      creates a broad variety of activity limitations for affected patients. After
      carpal tunnel release a significant alleviation of these limitations occurs
      within the first 3 months. Activity limitations seem not to be related to
      diabetes, but were more pronounced in women than in men, probably due to reduced
      grip strength.

PMID- 22366781
TI  - Discoidin domain receptor tyrosine kinases: new players in cancer progression.
AB  - Almost all human cancers display dysregulated expression and/or function of one
      or more receptor tyrosine kinases (RTKs). The strong causative association
      between altered RTK function and cancer progression has been translated into
      novel therapeutic strategies that target these cell surface receptors in cancer.
      Yet, the full spectrum of RTKs that may alter the oncogenic process is not
      completely understood. Accumulating evidence suggests that a unique set of RTKs
      known as the discoidin domain receptors (DDRs) play a key role in cancer
      progression by regulating the interactions of tumor cells with their surrounding
      collagen matrix. The DDRs are the only RTKs that specifically bind to and are
      activated by collagen. DDRs control cell and tissue homeostasis by acting as
      collagen sensors, transducing signals that regulate cell polarity, tissue
      morphogenesis, and cell differentiation. In cancer, DDRs are hijacked by tumor
      cells to disrupt normal cell-matrix communication and initiate pro-migratory and
      pro-invasive programs. Importantly, several cancer types exhibit DDR mutations,
      which are thought to alter receptor function and contribute to cancer
      progression. Other evidence suggests that the actions of DDRs in cancer are
      complex, either promoting or suppressing tumor cell behavior in a DDR
      type/isoform specific- and context-dependent manner. Thus, there is still a
      considerable gap in our knowledge of DDR actions in cancer tissues. This review
      summarizes and discusses the current knowledge on DDR expression and function in
      cancer. It is hoped that this effort will encourage more research into these
      poorly understood but unique RTKs, which have the potential of becoming novel
      therapeutic targets in cancer.

PMID- 22366783
TI  - De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter
      syndrome.
AB  - Brain malformations are individually rare but collectively common causes of
      developmental disabilities. Many forms of malformation occur sporadically and are
      associated with reduced reproductive fitness, pointing to a causative role for de
      novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well
      defined disorder characterized by distinct craniofacial features, ocular
      colobomata and neuronal migration defect. Using whole-exome sequencing of three
      proband-parent trios, we identified de novo missense changes in the cytoplasmic
      actin-encoding genes ACTB and ACTG1 in one and two probands, respectively.
      Sequencing of both genes in 15 additional affected individuals identified disease
      causing mutations in all probands, including two recurrent de novo alterations
      (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results
      confirm that trio-based exome sequencing is a powerful approach to discover genes
      causing sporadic developmental disorders, emphasize the overlapping roles of
      cytoplasmic actin proteins in development and suggest that Baraitser-Winter
      syndrome is the predominant phenotype associated with mutation of these two
      genes.

PMID- 22366784
TI  - Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer
      susceptibility in Japanese.
AB  - We have previously reported multiple loci associated with prostate cancer
      susceptibility in a Japanese population using a genome-wide association study
      (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped
      nine SNPs that were nominally associated with prostate cancer (P < 1 * 10(-4)) in
      our previous GWAS in three independent studies of prostate cancer in Japanese men
      (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta
      analysis of our previous GWAS and the replication studies, which included a total
      of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group,
      three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781;
      P = 1.10 * 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 * 10(-8)) and
      3p11.2 (rs2055109; P = 3.94 * 10(-8)). We also found suggestive evidence of
      association at a previously reported prostate cancer susceptibility locus at 2p11
      (rs2028898; P = 1.08 * 10(-7)). The identification of three new susceptibility
      loci should provide additional insight into the pathogenesis of prostate cancer
      and emphasizes the importance of conducting GWAS in diverse populations.

PMID- 22366785
TI  - Compound inheritance of a low-frequency regulatory SNP and a rare null mutation
      in exon-junction complex subunit RBM8A causes TAR syndrome.
AB  - The exon-junction complex (EJC) performs essential RNA processing tasks. Here, we
      describe the first human disorder, thrombocytopenia with absent radii (TAR),
      caused by deficiency in one of the four EJC subunits. Compound inheritance of a
      rare null allele and one of two low-frequency SNPs in the regulatory regions of
      RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this
      inheritance mechanism explained 53 of 55 cases (P < 5 * 10(-228)) of the rare
      congenital malformation syndrome. Of the 53 cases with this inheritance pattern,
      51 carried a submicroscopic deletion of 1q21.1 that has previously been
      associated with TAR, and two carried a truncation or frameshift null mutation in
      RBM8A. We show that the two regulatory SNPs result in diminished RBM8A
      transcription in vitro and that Y14 expression is reduced in platelets from
      individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an
      EJC defect as the cause of TAR syndrome.

PMID- 22366786
TI  - Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause
      limb-girdle muscular dystrophy.
AB  - Limb-girdle muscular dystrophy type 1D (LGMD1D) was linked to chromosome 7q36
      over a decade ago, but its genetic cause has remained elusive. Here we studied
      nine LGMD-affected families from Finland, the United States and Italy and
      identified four dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile
      changes in the ubiquitously expressed co-chaperone DNAJB6. Functional testing in
      vivo showed that the mutations have a dominant toxic effect mediated specifically
      by the cytoplasmic isoform of DNAJB6. In vitro studies demonstrated that the
      mutations increase the half-life of DNAJB6, extending this effect to the wild
      type protein, and reduce its protective anti-aggregation effect. Further, we show
      that DNAJB6 interacts with members of the CASA complex, including the
      myofibrillar myopathy-causing protein BAG3. Our data identify the genetic cause
      of LGMD1D, suggest that its pathogenesis is mediated by defective chaperone
      function and highlight how mutations in a ubiquitously expressed gene can exert
      effects in a tissue-, isoform- and cellular compartment-specific manner.

PMID- 22366788
TI  - Brain. Editorial.

PMID- 22366787
TI  - Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome.
AB  - Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive
      facial morphology, distal-limb anomalies and intellectual disability. We
      sequenced the exomes of ten individuals with NBS and identified heterozygous
      variants in SMARCA2 in eight of them. Extended molecular screening identified
      nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations
      were confirmed to be de novo when parental samples were available. SMARCA2
      encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling
      complex that is involved in the regulation of gene transcription. The mutations
      cluster within sequences that encode ultra-conserved motifs in the catalytic
      ATPase region of the protein. These alterations likely do not impair SWI/SNF
      complex assembly but may be associated with disrupted ATPase activity. The
      identification of SMARCA2 mutations in humans provides insight into the function
      of the Snf2 helicase family.

PMID- 22366789
TI  - Familial frontotemporal dementia and amyotrophic lateral sclerosis associated
      with the C9ORF72 hexanucleotide repeat.

PMID- 22366790
TI  - Episodic memory in frontotemporal dementia: a critical review.
AB  - This review offers a critical appraisal of the literature on episodic memory
      performance in frontotemporal dementia. Historically, description of patients
      diagnosed with what was then known as Pick's disease included the presence of
      memory deficits and an underlying amnestic syndrome was noted in some of these
      patients. Over the last 20 years, however, the clinical view has been that
      episodic memory processing is relatively intact in the frontotemporal dementia
      syndrome. In particular, patients with the subtypes of behavioural variant
      frontotemporal dementia and progressive non-fluent aphasia are reported to
      perform within normal limits on standard memory tests. In the third clinical
      presentation of frontotemporal dementia, semantic dementia, relatively intact
      episodic memory against a significantly impaired semantic memory was regarded as
      the hallmark. This position was instrumental in the development of clinical
      diagnostic criteria for frontotemporal dementia in which amnesia was explicitly
      listed as an exclusion criterion for the disease. The relative intactness of
      episodic memory, therefore, appeared to be a useful diagnostic marker to
      distinguish early frontotemporal dementia from Alzheimer's disease, in which
      early episodic memory disturbance remains the most common clinical feature. We
      argue that recent evidence questions the validity of preserved episodic memory in
      frontotemporal dementia, particularly in behavioural variant frontotemporal
      dementia. In semantic dementia, a complex picture emerges with preservation of
      some components of episodic memory, notably recognition-based visual memory and
      recall of recent autobiographical events. We propose a critical synthesis of
      recent neuropsychological evidence on retrograde and anterograde memory in light
      of neuroimaging and neuropathological findings, demonstrating involvement of
      medial temporal structures in frontotemporal dementia, structures known to be
      critical for episodic memory processing. We further argue that the multifactorial
      nature of most memory tests commonly used clinically fail to capture the memory
      deficits in frontotemporal dementia and that sensitive assessment tools of memory
      are needed. Together, recent clinical and experimental findings and the
      historical evidence represent a strong case for a re-evaluation of the importance
      of memory disturbance in the clinical diagnosis of frontotemporal dementia.

PMID- 22366791
TI  - Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion:
      clinical, neuroanatomical and neuropathological features.
AB  - An expanded hexanucleotide repeat in the C9ORF72 gene has recently been
      identified as a major cause of familial frontotemporal lobar degeneration and
      motor neuron disease, including cases previously identified as linked to
      chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and
      histopathological analysis of a C9ORF72 mutation case series in relation to other
      forms of genetically determined frontotemporal lobar degeneration ascertained at
      a specialist centre. Eighteen probands (19 cases in total) were identified,
      representing 35% of frontotemporal lobar degeneration cases with identified
      mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of
      the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified
      relevant family history. Families showed wide variation in clinical onset (43-68
      years) and duration (1.7-22 years). The most common presenting syndrome
      (comprising a half of cases) was behavioural variant frontotemporal dementia,
      however, there was substantial clinical heterogeneity across the C9ORF72 mutation
      cohort. Sixty per cent of cases developed clinical features consistent with motor
      neuron disease during the period of follow-up. Anxiety and agitation and memory
      impairment were prominent features (between a half to two-thirds of cases), and
      dominant parietal dysfunction was also frequent. Affected individuals showed
      variable magnetic resonance imaging findings; however, relative to healthy
      controls, the group as a whole showed extensive thinning of frontal, temporal and
      parietal cortices, subcortical grey matter atrophy including thalamus and
      cerebellum and involvement of long intrahemispheric, commissural and
      corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was
      significantly more symmetrical than progranulin mutations with significantly less
      temporal lobe involvement than microtubule-associated protein tau mutations.
      Neuropathological examination in six cases with C9ORF72 mutation from the
      frontotemporal lobar degeneration series identified histomorphological features
      consistent with either type A or B TAR DNA-binding protein-43 deposition;
      however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal
      cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of
      these cases, in contrast to the similar frequency of p62 and TAR DNA-binding
      protein-43 deposition in 53 control cases with frontotemporal lobar degeneration
      TAR DNA-binding protein. These findings corroborate the clinical importance of
      the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic
      and neuropathological features that could help to guide genetic testing, and
      suggest hypotheses for elucidating the neurobiology of a culprit subcortical
      network.

PMID- 22366792
TI  - Clinico-pathological features in amyotrophic lateral sclerosis with expansions in
      C9ORF72.
AB  - Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene
      causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron
      disease in both familial and sporadic cases. Initial reports indicate that this
      variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum
      is associated with transactive response DNA binding protein (TDP-43)
      proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype
      is not yet well characterized. We report the clinical and pathological phenotypes
      associated with pathogenic C9ORF72 mutations in a cohort of 563 cases from
      Northern England, including 63 with a family history of amyotrophic lateral
      sclerosis. One hundred and fifty-eight cases from the cohort (21 familial, 137
      sporadic) were post-mortem brain and spinal cord donors. We screened DNA for the
      C9ORF72 mutation, reviewed clinical case histories and undertook pathological
      evaluation of brain and spinal cord. Control DNA samples (n = 361) from the same
      population were also screened. The C9ORF72 intronic expansion was present in 62
      cases [11% of the cohort; 27/63 (43%) familial, 35/500 (7%) cases with sporadic
      amyotrophic lateral sclerosis/motor neuron disease]. Disease duration was
      significantly shorter in cases with C9ORF72-related amyotrophic lateral sclerosis
      (30.5 months) compared with non-C9ORF72 amyotrophic lateral sclerosis/motor
      neuron disease (36.3 months, P < 0.05). C9ORF72 cases included both limb and
      bulbar onset disease and all cases showed combined upper and lower motor neuron
      degeneration (amyotrophic lateral sclerosis). Thus, clinically, C9ORF72 cases
      show the features of a relatively rapidly progressive, but otherwise typical,
      variant of amyotrophic lateral sclerosis associated with both familial and
      sporadic presentations. Dementia was present in the patient or a close family
      member in 22/62 cases with C9ORF72 mutation (35%) based on diagnoses established
      from retrospective clinical case note review that may underestimate significant
      cognitive changes in late disease. All the C9ORF72 mutation cases showed
      classical amyotrophic lateral sclerosis pathology with TDP-43 inclusions in
      spinal motor neurons. Neuronal cytoplasmic inclusions and glial inclusions
      positive for p62 immunostaining in non-motor regions were strongly over
      represented in the C9ORF72 cases. Extra-motor pathology in the frontal cortex (P
      < 0.0005) and the hippocampal CA4 subfield neurons (P < 0.0005) discriminated
      C9ORF72 cases strongly from the rest of the cohort. Inclusions in CA4 neurons
      were not present in non-C9ORF72 cases, indicating that this pathology predicts
      mutation status.

PMID- 22366793
TI  - Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis
      associated with the GGGGCC repeat expansion in C9ORF72.
AB  - Numerous kindreds with familial frontotemporal dementia and/or amyotrophic
      lateral sclerosis have been linked to chromosome 9, and an expansion of the
      GGGGCC hexanucleotide repeat in the non-coding region of chromosome 9 open
      reading frame 72 has recently been identified as the pathogenic mechanism. We
      describe the key characteristics in the probands and their affected relatives who
      have been evaluated at Mayo Clinic Rochester or Mayo Clinic Florida in whom the
      hexanucleotide repeat expansion were found. Forty-three probands and 10 of their
      affected relatives with DNA available (total 53 subjects) were shown to carry the
      hexanucleotide repeat expansion. Thirty-six (84%) of the 43 probands had a
      familial disorder, whereas seven (16%) appeared to be sporadic. Among examined
      subjects from the 43 families (n = 63), the age of onset ranged from 33 to 72
      years (median 52 years) and survival ranged from 1 to 17 years, with the age of
      onset <40 years in six (10%) and >60 in 19 (30%). Clinical diagnoses among
      examined subjects included behavioural variant frontotemporal dementia with or
      without parkinsonism (n = 30), amyotrophic lateral sclerosis (n = 18),
      frontotemporal dementia/amyotrophic lateral sclerosis with or without
      parkinsonism (n = 12), and other various syndromes (n = 3). Parkinsonism was
      present in 35% of examined subjects, all of whom had behavioural variant
      frontotemporal dementia or frontotemporal dementia/amyotrophic lateral sclerosis
      as the dominant clinical phenotype. No subject with a diagnosis of primary
      progressive aphasia was identified with this mutation. Incomplete penetrance was
      suggested in two kindreds, and the youngest generation had significantly earlier
      age of onset (>10 years) compared with the next oldest generation in 11 kindreds.
      Neuropsychological testing showed a profile of slowed processing speed, complex
      attention/executive dysfunction, and impairment in rapid word retrieval.
      Neuroimaging studies showed bilateral frontal abnormalities most consistently,
      with more variable degrees of parietal with or without temporal changes; no case
      had strikingly focal or asymmetric findings. Neuropathological examination of 14
      patients revealed a range of transactive response DNA binding protein molecular
      weight 43 pathology (10 type A and four type B), as well as ubiquitin-positive
      cerebellar granular neuron inclusions in all but one case. Motor neuron
      degeneration was detected in nine patients, including five patients without ante
      mortem signs of motor neuron disease. While variability exists, most cases with
      this mutation have a characteristic spectrum of demographic, clinical,
      neuropsychological, neuroimaging and especially neuropathological findings.

PMID- 22366794
TI  - Clinical characteristics of patients with familial amyotrophic lateral sclerosis
      carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72.
AB  - A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72,
      a gene located on chromosome 9p21, has been recently reported to be responsible
      for ~40% of familial amyotrophic lateral sclerosis cases of European ancestry.
      The aim of the current article was to describe the phenotype of amyotrophic
      lateral sclerosis cases carrying the expansion by providing a detailed clinical
      description of affected cases from representative multi-generational kindreds,
      and by analysing the age of onset, gender ratio and survival in a large cohort of
      patients with familial amyotrophic lateral sclerosis. We collected DNA and
      analysed phenotype data for 141 index Italian familial amyotrophic lateral
      sclerosis cases (21 of Sardinian ancestry) and 41 German index familial
      amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected
      in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian
      ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral
      sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees
      and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On
      average, children developed disease 7.0 years earlier than their parents
      [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation
      10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms
      manifested by the child: of the 13 cases where the affected parent had an
      amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia,
      the affected child also developed amyotrophic lateral sclerosis-frontotemporal
      dementia in nine cases. When compared with patients carrying mutations of other
      amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had
      commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion
      cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non
      C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among
      cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients
      carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and
      longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7
      2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most
      frequent mutation in our large cohort of patients with familial amyotrophic
      lateral sclerosis of Italian, Sardinian and German ancestry. Together with
      mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for ~60% of
      familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72
      hexanucleotide repeat expansions present some phenotypic differences compared
      with patients with mutations of other genes or with unknown mutations, namely a
      high incidence of bulbar-onset disease and comorbidity with frontotemporal
      dementia. Their pedigrees typically display a high frequency of cases with pure
      frontotemporal dementia, widening the concept of familial amyotrophic lateral
      sclerosis.

PMID- 22366795
TI  - Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau,
      progranulin and sporadics.
AB  - A major recent discovery was the identification of an expansion of a non-coding
      GGGGCC hexanucleotide repeat in the C9ORF72 gene in patients with frontotemporal
      dementia and amyotrophic lateral sclerosis. Mutations in two other genes are
      known to account for familial frontotemporal dementia: microtubule-associated
      protein tau and progranulin. Although imaging features have been previously
      reported in subjects with mutations in tau and progranulin, no imaging features
      have been published in C9ORF72. Furthermore, it remains unknown whether there are
      differences in atrophy patterns across these mutations, and whether regional
      differences could help differentiate C9ORF72 from the other two mutations at the
      single-subject level. We aimed to determine the regional pattern of brain atrophy
      associated with the C9ORF72 gene mutation, and to determine which regions best
      differentiate C9ORF72 from subjects with mutations in tau and progranulin, and
      from sporadic frontotemporal dementia. A total of 76 subjects, including 56 with
      a clinical diagnosis of behavioural variant frontotemporal dementia and a
      mutation in one of these genes (19 with C9ORF72 mutations, 25 with tau mutations
      and 12 with progranulin mutations) and 20 sporadic subjects with behavioural
      variant frontotemporal dementia (including 50% with amyotrophic lateral
      sclerosis), with magnetic resonance imaging were included in this study. Voxel
      based morphometry was used to assess and compare patterns of grey matter atrophy.
      Atlas-based parcellation was performed utilizing the automated anatomical
      labelling atlas and Statistical Parametric Mapping software to compute volumes of
      37 regions of interest. Hemispheric asymmetry was calculated. Penalized
      multinomial logistic regression was utilized to create a prediction model to
      discriminate among groups using regional volumes and asymmetry score. Principal
      component analysis assessed for variance within groups. C9ORF72 was associated
      with symmetric atrophy predominantly involving dorsolateral, medial and
      orbitofrontal lobes, with additional loss in anterior temporal lobes, parietal
      lobes, occipital lobes and cerebellum. In contrast, striking anteromedial
      temporal atrophy was associated with tau mutations and temporoparietal atrophy
      was associated with progranulin mutations. The sporadic group was associated with
      frontal and anterior temporal atrophy. A conservative penalized multinomial
      logistic regression model identified 14 variables that could accurately classify
      subjects, including frontal, temporal, parietal, occipital and cerebellum volume.
      The principal component analysis revealed similar degrees of heterogeneity within
      all disease groups. Patterns of atrophy therefore differed across subjects with
      C9ORF72, tau and progranulin mutations and sporadic frontotemporal dementia. Our
      analysis suggested that imaging has the potential to be useful to help
      differentiate C9ORF72 from these other groups at the single-subject level.

PMID- 22366796
TI  - Acetylated tau, a novel pathological signature in Alzheimer's disease and other
      tauopathies.
AB  - The microtubule-binding protein, tau, is the major component of neurofibrillary
      inclusions characteristic of Alzheimer's disease and related neurodegenerative
      tauopathies. When tau fibrillizes, it undergoes abnormal post-translational
      modifications resulting in decreased solubility and altered microtubule
      stabilizing properties. Recently, we reported that the abnormal acetylation of
      tau at lysine residue 280 is a novel, pathological post-translational
      modification. Here, we performed detailed immunohistochemistry to further examine
      acetylated-tau expression in Alzheimer's disease and other major tauopathies.
      Immunohistochemistry using a polyclonal antibody specific for acetylated-tau at
      lysine 280 was conducted on 30 post-mortem central nervous system regions from
      patients with Alzheimer's disease (10 patients), corticobasal degeneration (5
      patients), and progressive supranuclear palsy (5 patients). Acetylated-tau
      pathology was compared with the sequential emergence of other tau modifications
      in the Alzheimer's disease hippocampus using monoclonal antibodies to multiple
      well-characterized tau epitopes. All cases studied showed significant acetylated
      tau pathology in a distribution pattern similar to hyperphosphorylated-tau.
      Acetylated-tau pathology was largely in intracellular, thioflavin-S-positive tau
      inclusions in Alzheimer's disease, and also thioflavin-S-negative pathology in
      corticobasal degeneration and progressive supranuclear palsy. Acetylated-tau was
      present throughout all stages of Alzheimer's disease pathology, but was more
      prominently associated with pathological tau epitopes in moderate to severe-stage
      cases. These temporal and morphological immunohistochemical features suggest
      acetylation of tau at this epitope is preceded by early modifications, including
      phosphorylation, and followed by later truncation events and cell death in
      Alzheimer's disease. Acetylation of tau at lysine 280 is a pathological
      modification that may contribute to tau-mediated neurodegeneration by both
      augmenting losses of normal tau properties (reduced solubility and microtubule
      assembly) as well as toxic gains of function (increased tau fibrillization).
      Thus, inhibiting tau acetylation could be a disease-modifying target for drug
      discovery target in tauopathies.

PMID- 22366797
TI  - Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant
      transgenic mice.
AB  - Mutations in the charged multivesicular body protein 2B (CHMP2B) gene cause
      frontotemporal lobar degeneration. The mutations lead to C-terminal truncation of
      the CHMP2B protein. We generated Chmp2b knockout mice and transgenic mice
      expressing either wild-type or C-terminally truncated mutant CHMP2B. The
      transgenic CHMP2B mutant mice have decreased survival and show progressive
      neurodegenerative changes including gliosis and increasing accumulation of p62-
      and ubiquitin-positive inclusions. The inclusions are negative for the TAR DNA
      binding protein 43 and fused in sarcoma proteins, mimicking the inclusions
      observed in patients with CHMP2B mutation. Mice transgenic for mutant CHMP2B also
      develop an early and progressive axonopathy characterized by numerous amyloid
      precursor protein-positive axonal swellings, implicating altered axonal function
      in disease pathogenesis. These findings were not observed in Chmp2b knockout mice
      or in transgenic mice expressing wild-type CHMP2B, indicating that CHMP2B
      mutations induce degenerative changes through a gain of function mechanism. These
      data describe the first mouse model of dementia caused by CHMP2B mutation and
      provide new insights into the mechanisms of CHMP2B-induced neurodegeneration.

PMID- 22366798
TI  - Correlates of spreading depolarization in human scalp electroencephalography.
AB  - It has been known for decades that suppression of spontaneous scalp
      electroencephalographic activity occurs during ischaemia. Trend analysis for such
      suppression was found useful for intraoperative monitoring during carotid
      endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after
      aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such
      suppression of activity has remained unclear. In five patients with aneurismal
      subarachnoid haemorrhage and four patients with decompressive hemicraniectomy
      after malignant hemispheric stroke due to middle cerebral artery occlusion, we
      here performed simultaneously full-band direct and alternating current
      electroencephalography at the scalp and direct and alternating current
      electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275
      slow potential changes, identifying spreading depolarizations, were recorded
      electrocorticographically over 694 h. Visual inspection of time-compressed scalp
      electroencephalography identified 193 (70.2%) slow potential changes [amplitude: 
      272 (-174, -375) uV (median quartiles), duration: 5.4 (4.0, 7.1) min,
      electrocorticography-electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals
      between successive spreading depolarizations were significantly shorter for
      depolarizations with electroencephalographically identified slow potential change
      [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009].
      Electroencephalography was thus more likely to display slow potential changes of
      clustered than isolated spreading depolarizations. In contrast to
      electrocorticography, no spread of electroencephalographic slow potential changes
      was seen, presumably due to superposition of volume-conducted
      electroencephalographic signals from widespread cortical generators. In two of
      five patients with subarachnoid haemorrhage, serial magnetic resonance imaging
      revealed large delayed infarcts at the recording site, while electrocorticography
      showed clusters of spreading depolarizations with persistent depression of
      spontaneous activity. Alternating current electroencephalography similarly
      displayed persistent depression of spontaneous activity, and direct current
      electroencephalography slow potential changes riding on a shallow negative
      ultraslow potential. Isolated spreading depolarizations with depression of both
      spontaneous electrocorticographic and electroencephalographic activity displayed
      significantly longer intervals between successive spreading depolarizations than
      isolated depolarizations with only depression of electrocorticographic activity
      [44.0 (28.0, 132.0) min, n = 96, versus 30.0 (26.5, 51.5) min, n = 109, P =
      0.001]. This suggests fusion of electroencephalographic depression periods at
      high depolarization frequency. No propagation of electroencephalographic
      depression was seen between scalp electrodes. Durations/magnitudes of isolated
      electroencephalographic and corresponding electrocorticographic depression
      periods correlated significantly. Fewer spreading depolarizations were recorded
      in patients with malignant hemispheric stroke but characteristics were similar to
      those after subarachnoid haemorrhage. In conclusion, spreading depolarizations
      and depressions of spontaneous activity display correlates in time-compressed
      human scalp direct and alternating current electroencephalography that may serve
      for their non-invasive detection.

PMID- 22366800
TI  - A representative cohort of patients with non-progressive multiple sclerosis at
      the age of normal life expectancy.
AB  - Multiple sclerosis may have a non-progressive symptomatology for decades;
      however, it is not clear whether the disease activity may abate completely. We
      identified a cohort of patients, resident in Gothenburg at the time of disease
      onset, between the years 1950-64 (n = 307). These geographical and temporal
      restrictions, along with favourable conditions for a 'spider' epidemiological
      study, were optimal for an unbiased selection; this 15-year incidence cohort was
      essentially followed prospectively for 37-59 years after onset. The shortest
      follow-up time for patients without primary or secondary progression was 45
      years. For patients with an initial relapsing-remitting course and multiple
      sclerosis diagnosis according to the Poser criteria (n = 202), the probability of
      non-progressive disease after 40 years was 22% (standard error 3.0%), and after
      50 years it was 14% (standard error 3.2%). For attack onset including patients
      with possible multiple sclerosis, the corresponding probabilities after 40 and 50
      years were 35% (standard error 3.3%) and 28% (standard error 3.5%), respectively.
      At the last follow-up in 2009-10, when patients reached the average age of the
      Swedish population life expectancy, only 13 patients from the multiple sclerosis
      diagnosis cohort, according to the Poser criteria, remained alive and non
      progressive. Their annualized attack frequency diminished with time from 0.29 to
      0.015. These patients had been functioning well socially. Nine patients had an
      Expanded Disability Status Scale score of 0-2.5, and four patients had a score of
      3 or 3.5, with deficits dating back to attacks decades ago. Eight patients
      participated in a complete neuropsychological examination, which showed a slight
      difference (P < 0.01) concerning verbal memory and executive function compared to
      an age and socially matched reference group, whereas results for five other
      cognitive domains were within the normal range. Magnetic resonance images
      fulfilled the Barkhof-Tintore criteria for multiple sclerosis in 10 of 11
      patients, with conspicuously few subcortical lesions relative to extensive
      periventricular lesions and lesions extending from the inferior midline aspect of
      the corpus callosum. Prediction of the non-progressive stage was possible with
      moderate hazard ratios and low sensitivity. Early features that predicted a non
      progressive course were complete remission of the onset attack, low or moderate
      initial relapse frequency and-when the patients with possible multiple sclerosis
      were included-dominating afferent symptoms. The clinical disease activity had
      abated in these 13 patients, with the caveat that transition to secondary
      progression continued to occur after four decades, albeit with decreasing risk.

PMID- 22366801
TI  - Functionally specific oscillatory activity correlates between visual and auditory
      cortex in the blind.
AB  - Many studies have shown that the visual cortex of blind humans is activated in
      non-visual tasks. However, the electrophysiological signals underlying this cross
      modal plasticity are largely unknown. Here, we characterize the neuronal
      population activity in the visual and auditory cortex of congenitally blind
      humans and sighted controls in a complex cognitive task. We recorded
      magnetoencephalographic responses from participants performing semantic
      categorization of meaningful sounds that followed the presentation of a
      semantically related or unrelated haptic object. Source analysis of the
      spectrally resolved magnetoencephalography data revealed that: (i) neuronal
      responses to sounds were stronger and longer lasting in the auditory cortex of
      blind subjects; (ii) auditory stimulation elicited strong oscillatory responses
      in the visual cortex of blind subjects that closely resembled responses to visual
      stimulation in sighted humans; (iii) the signal in the gamma frequency range was
      modulated by semantic congruency between the sounds and the preceding haptic
      objects; and (iv) signal power in the gamma range was correlated on a trial-by
      trial basis between auditory and visual cortex in blind subjects, and the
      strength of this correlation was modulated by semantic congruency. Our results
      suggest that specifically oscillatory activity in the gamma range reflects non
      visual processing in the visual cortex of blind individuals. Moreover, our
      results provide evidence that the deprived visual cortex is functionally
      integrated into a larger network that serves non-visual functions.

PMID- 22366799
TI  - NADPH oxidase expression in active multiple sclerosis lesions in relation to
      oxidative tissue damage and mitochondrial injury.
AB  - Multiple sclerosis is a chronic inflammatory disease of the central nervous
      system, associated with demyelination and neurodegeneration. The mechanisms of
      tissue injury are poorly understood, but recent data suggest that mitochondrial
      injury may play an important role in this process. Mitochondrial injury can be
      triggered by reactive oxygen and nitric oxide species, and we recently provided
      evidence for oxidative damage of oligodendrocytes and dystrophic axons in early
      stages of active multiple sclerosis lesions. In this study, we identified
      potential sources of reactive oxygen and nitrogen species through gene expression
      in carefully staged and dissected lesion areas and by immunohistochemical
      analysis of protein expression. Genome-wide microarrays confirmed mitochondrial
      injury in active multiple sclerosis lesions, which may serve as an important
      source of reactive oxygen species. In addition, we found differences in the gene
      expression levels of various nicotinamide adenine dinucleotide phosphate oxidase
      subunits between initial multiple sclerosis lesions and control white matter.
      These results were confirmed at the protein level by means of
      immunohistochemistry, showing upregulation of the subunits gp91phox, p22phox,
      p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide
      adenine dinucleotide phosphate oxidase organizer 1 in activated microglia in
      classical active as well as slowly expanding lesions. The subunits gp91phox and
      p22phox were constitutively expressed in microglia and were upregulated in the
      initial lesion. In contrast, p47phox, nicotinamide adenine dinucleotide phosphate
      oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1
      expression were more restricted to the zone of initial damage or to lesions from
      patients with acute or early relapsing/remitting multiple sclerosis. Double
      labelling showed co-expression of the nicotinamide adenine dinucleotide phosphate
      oxidase subunits in activated microglia and infiltrated macrophages, suggesting
      the assembly of functional complexes. Our data suggest that the inflammation
      associated oxidative burst in activated microglia and macrophages plays an
      important role in demyelination and free radical-mediated tissue injury in the
      pathogenesis of multiple sclerosis.

PMID- 22366802
TI  - To trust or not to trust: the dynamics of social interaction in psychosis.
AB  - Psychotic illness is a disorder of social interaction unique to humans. However,
      up to now research has failed to pin down the exact determinants of the complex
      and interactive processes associated with the development of trust and
      reciprocity in psychosis. Utilizing a novel multi-round version of an interactive
      trust game experiment, we show that patients with psychosis and healthy relatives
      with a heightened risk for the illness exhibit lower baseline levels of trust
      compared with healthy controls. This effect partly overlapped with a reduced
      general intelligence. Furthermore, patients were unable to modify their trusting
      behaviour neither in response to information about the general trustworthiness of
      their interaction partner, nor in response to their partners' specific direct
      behavioural feedback. Relatives, in contrast, modified their trusting behaviour
      towards similar levels as healthy subjects in response to both. The results show
      that behavioural flexibility in response to socially relevant information is a
      critical determinant of success in the instantiation and maintenance of social
      relationships. A lack thereof may drive social dysfunction and the progression
      from subclinical symptoms to a full-blown psychosis. This offers a testable
      mechanistic hypothesis for progression from prodrome to psychotic illness, and
      may provide a therapeutic avenue to grapple the psychotic symptoms of social
      dysfunction.

PMID- 22366803
TI  - Breastfeeding in Byzantine icon art.
AB  - INTRODUCTION: The Mary Galaktotrophousa is a representation of the Virgin
      breastfeeding the infant Jesus. MATERIALS: The origin of this theme goes back to
      Antiquity when images of gods feeding humans were considered as an example that
      should be imitated by human. In the early days of Christianity, the Fathers of
      the Church recognized on the feature of Mary the ideal exemplary of maternity.
      CONCLUSION: The image of the Virgin breastfeeding the Holy Child, except the
      theological interpretation of the gesture, underline the fact that breastfeeding
      represents one of the most substantial gestures in the woman nature.

PMID- 22366804
TI  - Using a titanium-coated polypropylene mesh (TiLOOP((r)) Bra) for implant-based
      breast reconstruction: case report and histological analysis.

PMID- 22366805
TI  - Laparoscopic and laparotomic approaches for endometrial cancer treatment: a
      comprehensive review.
AB  - OBJECTIVE: Endometrial cancer (EC) is the most common gynecological malignancy in
      the developed world, particularly among postmenopausal women. Endoscopic surgery
      is gaining more popularity among surgeons as a safe and feasible option for
      treatment of endometrial carcinoma, providing the possibility of adequate lymph
      node excision. METHODS: A comprehensive review. RESULTS: The advantages of
      laparoscopy prevail over laparotomy and authors report lower peri-operative
      complication rates, less blood loss, lower transfusion rates, and shorter
      hospital stay, as well as a better quality of life (QoL) after laparoscopic
      surgery, in contrast to conventional abdominal surgery. This was confirmed by a
      meta-analysis of four randomized controlled studies. This is also true for obese
      risky patients to whom laparotomies carry indolent side effects. In addition,
      with more training and experience this procedure would be even more feasible and
      safer. CONCLUSIONS: Because of the increasing importance of economic efficiency
      in health care, the endoscopic approach will continue to play a more important
      role in the future treatment of EC providing a better treatment option for the
      coming patients. As a promising therapeutical option, it should be offered to all
      patients with an early-stage EC.

PMID- 22366806
TI  - Three- and four-dimensional volume-rendered imaging of situs inversus totalis
      with inversion mode.

PMID- 22366807
TI  - Bilateral interhemispheric subdural hematoma after accidental lumbar puncture and
      epidural blood patch.

PMID- 22366808
TI  - Enchondromas in children: imaging appearance with pathological correlation.
AB  - OBJECTIVE: Enchondromas are benign lesions that may present with nonspecific
      features on imaging in children. Correlation of histology with imaging findings
      is often required to make the final diagnosis of a benign lesion. The aim of this
      study was to review imaging and pathological findings of enchondromas in
      children. MATERIALS AND METHODS: Imaging examinations of 12 enchondromas in 11
      patients (median age 14 years) were retrospectively reviewed. Imaging evaluation
      included an assessment of lesion size, relationship to the growth plate,
      mineralization, matrix and periosteal reaction, intrinsic MR signal
      characteristics, and intraosseous and soft-tissue edema. Pathological findings
      were reviewed. RESULTS: Lesions were located in the phalanx in 33% (4 out of 12),
      metacarpal in 25% (3 out of 12), femur in 33% (4 out of 12) and tibia in 8% cases
      (1 out of 12). The mean size was 28 mm (range, 11-70 mm). Matrix mineralization
      in a typical "rings-and-arcs" pattern was observed in 20% of the lesions with
      available radiographs/CT (2 out of 10). Lesions were expansive with endosteal
      scalloping in 75% of cases (9 out 12) and contacted the growth plate in 50% of
      cases (6 out of 12). All enchondromas in which MR imaging was available (5 out of
      5) demonstrated typical cartilaginous matrix of lobules of high T2 signal, low T1
      signal, and peripheral enhancement. CONCLUSION: Enchondromas in children are
      relatively large lesions, with frequent endosteal scalloping and rare matrix
      mineralization.

PMID- 22366809
TI  - Enteric hyperoxaluria, recurrent urolithiasis, and systemic oxalosis in patients
      with Crohn's disease.
AB  - BACKGROUND: Prevalence of recurrent calcium-oxalate (CaOx) urolithiasis (UL) is
      up to fivefold higher in Crohn's disease than in the general population.
      Treatment options are scarce and the risk of recurrent UL or progressive renal
      CaOx deposition, (oxalosis) based early end-stage renal failure (ESRF),
      subsequent systemic oxalosis, and recurrence in the kidney graft is pronounced.
      We aimed to find proof that secondary hyperoxaluria is the main risk factor for
      the devastating course and correlates with intestinal oxalate absorption.
      METHODS: 24-h urines were collected and analyzed for urinary oxalate (Uox) in 27
      pediatric (6-18 years) and 19 adult patients (20-62 years). In the 21 patients (8
      adults and 13 children) with hyperoxaluria a [(13)C(2)]oxalate absorption test
      was performed under standardized dietary conditions. RESULTS: Mean Uox was
      significantly higher in patients with UL or oxalosis (0.92 +/- 0.57) compared
      with those without (0.53 +/- 0.13 mmol/1.73 m(2)/24 h, p<0.05, normal < 0.5).
      Hyperoxaluria then significantly correlated with intestinal oxalate absorption
      (p< 0.05). CONCLUSION: As UL/oxalosis has major implications for the general
      health in patients with Crohn's disease (ESRF and systemic oxalosis), new
      medication, e.g. to reduce intestinal oxalate absorption, is definitely needed.

PMID- 22366810
TI  - Rheumatoid arthritis and the era of biologic therapy.
AB  - Biologic disease modifying anti-rheumatic drugs have transformed the management
      of rheumatoid arthritis (RA) since their introduction into clinical practice over
      a decade ago. Following large-scale clinical trials, a number of biologics, with
      different mechanisms of action, have been licensed for the condition. In this
      review, we will summarise the current evidence for biologic use in RA with an
      emphasis on their efficacy and tolerability. In addition, we will provide a
      commentary on the current limitations and unmet needs in this area and discuss
      the future of biologic intervention.

PMID- 22366811
TI  - Lactobacillus casei combats acid stress by maintaining cell membrane
      functionality.
AB  - Lactobacillus casei strains have traditionally been recognized as probiotics and
      frequently used as adjunct culture in fermented dairy products where lactic acid
      stress is a frequently encountered environmental condition. We have investigated
      the effect of lactic acid stress on the cell membrane of L. casei Zhang [wild
      type (WT)] and its acid-resistant mutant Lbz-2. Both strains were grown under
      glucose-limiting conditions in chemostats; following challenge by low pH, the
      cell membrane stress responses were investigated. In response to acid stress,
      cell membrane fluidity decreased and its fatty acid composition changed to reduce
      the damage caused by lactic acid. Compared with the WT, the acid-resistant mutant
      exhibited numerous survival advantages, such as higher membrane fluidity, higher
      proportions of unsaturated fatty acids, and higher mean chain length. In
      addition, cell integrity analysis showed that the mutant maintained a more intact
      cellular structure and lower membrane permeability after environmental
      acidification. These results indicate that alteration in membrane fluidity, fatty
      acid distribution, and cell integrity are common mechanisms utilized by L. casei
      to withstand severe acidification and to reduce the deleterious effect of lactic
      acid on the cell membrane. This detailed comparison of cell membrane responses
      between the WT and mutant add to our knowledge of the acid stress adaptation and
      thus enable new strategies to be developed aimed at improving the industrial
      performance of this species under acid stress.

PMID- 22366812
TI  - Identification of quantitative trait loci (QTL) for resistance to Fusarium crown
      rot (Fusarium pseudograminearum) in multiple assay environments in the Pacific
      Northwestern US.
AB  - Fusarium crown rot (FCR), caused by Fusarium pseudograminearum and F. culmorum,
      reduces wheat (Triticum aestivum L.) yields in the Pacific Northwest (PNW) of the
      US by as much as 35%. Resistance to FCR has not yet been discovered in currently
      grown PNW wheat cultivars. Several significant quantitative trait loci (QTL) for
      FCR resistance have been documented on chromosomes 1A, 1D, 2B, 3B, and 4B in
      resistant Australian cultivars. Our objective was to identify QTL and tightly
      linked SSR markers for FCR resistance in the partially resistant Australian
      spring wheat cultivar Sunco using PNW isolates of F. pseudograminerarum in
      greenhouse and field based screening nurseries. A second objective was to compare
      heritabilities of FCR resistance in multiple types of disease assaying
      environments (seedling, terrace, and field) using multiple disease rating
      methods. Two recombinant inbred line (RIL) mapping populations were derived from
      crosses between Sunco and PNW spring wheat cultivars Macon and Otis. The
      Sunco/Macon population comprised 219 F(6):F(7) lines and the Sunco/Otis
      population comprised 151 F(5):F(6) lines. Plants were inoculated with a single
      PNW F. pseudograminearum isolate (006-13) in growth room (seedling), outdoor
      terrace (adult) and field (adult) assays conducted from 2008 through 2010. Crown
      and lower stem tissues of seedling and adult plants were rated for disease
      severity on several different scales, but mainly on a numeric scale from 0 to 10
      where 0 = no discoloration and 10 = severe disease. Significant QTL were
      identified on chromosomes 2B, 3B, 4B, 4D, and 7A with LOD scores ranging from 3
      to 22. The most significant and consistent QTL across screening environments was
      located on chromosome 3BL, inherited from the PNW cultivars Macon and Otis, with
      maximum LOD scores of 22 and 9 explaining 36 and 23% of the variation,
      respectively for the Sunco/Macon and Sunco/Otis populations. The SSR markers
      Xgwm247 and Xgwm299 flank these QTL and are being validated for use in marker
      assisted selection for FCR resistance. This is the first report of QTL associated
      with FCR resistance in the US.

PMID- 22366813
TI  - The distal portion of the short arm of wheat (Triticum aestivum L.) chromosome 5D
      controls endosperm vitreosity and grain hardness.
AB  - Kernel vitreosity is an important trait of wheat grain, but its developmental
      control is not completely known. We developed back-cross seven (BC(7)) near
      isogenic lines in the soft white spring wheat cultivar Alpowa that lack the
      distal portion of chromosome 5D short arm. From the final back-cross, 46
      BC(7)F(2) plants were isolated. These plants exhibited a complete and perfect
      association between kernel vitreosity (i.e. vitreous, non-vitreous or mixed) and
      Single Kernel Characterization System (SKCS) hardness. Observed segregation of
      10:28:7 fit a 1:2:1 Chi-square. BC(7)F(2) plants classified as heterozygous for
      both SKCS hardness and kernel vitreosity (n = 29) were selected and a single
      vitreous and non-vitreous kernel were selected, and grown to maturity and
      subjected to SKCS analysis. The resultant phenotypic ratios were, from non
      vitreous kernels, 23:6:0, and from vitreous kernels, 0:1:28,
      soft:heterozygous:hard, respectively. Three of these BC(7)F(2) heterozygous
      plants were selected and 40 kernels each drawn at random, grown to maturity and
      subjected to SKCS analysis. Phenotypic segregation ratios were 7:27:6, 11:20:9,
      and 3:28:9, soft:heterozygous:hard. Chi-square analysis supported a 1:2:1
      segregation for one plant but not the other two, in which cases the two
      homozygous classes were under-represented. Twenty-two paired BC(7)F(2):F(3) full
      sibs were compared for kernel hardness, weight, size, density and protein
      content. SKCS hardness index differed markedly, 29.4 for the lines with a
      complete 5DS, and 88.6 for the lines possessing the deletion. The soft non
      vitreous kernels were on average significantly heavier, by nearly 20%, and were
      slightly larger. Density and protein contents were similar, however. The results
      provide strong genetic evidence that gene(s) on distal 5DS control not only
      kernel hardness but also the manner in which the endosperm develops, viz. whether
      it is vitreous or non-vitreous.

PMID- 22366814
TI  - ETS transcription factors and prostate cancer: the role of the family prototype
      ETS-1 (review).
AB  - The ETS family of transcription factors is known to play important roles in
      various biological processes such as development, differentiation, proliferation,
      apoptosis, migration, tissue remodeling, invasion and angiogenesis in various
      cell types including B cells, endothelial cells, fibroblasts as well as diverse
      neoplastic cells. In prostate cancer, recurrent gene fusions involving members of
      the ETS family are frequently reported. ETS-1, the prototype of the ETS family,
      is expressed in different cell types and is known to play various roles during
      both physiological and pathological conditions. In this review, we focus on
      studies investigating the role of ETS-1 in prostate cancer.

PMID- 22366815
TI  - Anorexia nervosa and the Val158Met polymorphism of the COMT gene:  meta-analysis
      and new data.
AB  - OBJECTIVES: This study aimed to test the association between the Val158Met
      polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia
      nervosa (AN). METHODS: First, an association study on two cohorts (306 cases and
      1009 controls from Utrecht, and 174 cases and 466 controls from Leiden/NTR) was
      performed. Subsequently, the results were integrated into a meta-analysis,
      together with all the case-control and family-based studies, which were testing
      the same hypothesis and were available in the literature. Altogether, eight
      studies (11 datasets) were included in this meta-analysis, with a total of 2021
      cases, 2848 controls, and 89 informative (heterozygous) trios. RESULTS: The
      present association studies found no association between AN and rs4680 when
      testing the allelic contrast [Utrecht odds ratio (OR)=1.14, P=0.14; Leiden
      OR=1.02, P=0.85]. There was an indication of an association under the dominant
      model of genetic effect in the Utrecht cohort (for the Met allele, OR=1.42,
      P=0.03). Nevertheless, the meta-analyses of both the allelic contrast and the
      dominant effect were nonsignificant (the allelic pooled OR=1.03, P=0.42 and the
      dominant pooled OR=1.1, P=0.18). The meta-analyses were performed under the fixed
      effect model and there was no significant heterogeneity among the effect sizes.
      CONCLUSION: Meta-analytically combined evidence from the present genotypings and
      the literature search shows that the effect sizes are homogeneous across studies
      and that rs4680 is not associated with AN.

PMID- 22366816
TI  - Characterization of maleimide dimers in photo-cross-linked copolyimide films.
AB  - Copolyimide membranes are established materials for the separation of gaseous and
      liquid mixtures. Cross-linking of the polymer strands improves the physical and
      chemical stability. The photo-cross-linking of a 6FDA-ODA/6FDA-DABA 4 : 1
      copolyimide membrane containing maleimide side groups as linker was investigated
      by FTIR spectroscopy. IR absorption spectra of the copolyimide backbone, 3
      hydroxypropyldimethyl maleimide and the copolyimide functionalized with 3
      hydroxypropyldimethyl maleimide were measured before and after different
      irradiation times and compared to each other. For band assignment a normal mode
      analysis was performed. The backbone of the polymer and the maleimide linker can
      be well distinguished due to their different spectral band positions. Only the
      films containing a maleimide moiety perform a photoreaction, the polymer backbone
      does not interfere. Based on the difference spectra and the results of the DFT
      calculations it was shown that the trans- and the cis-cycloadduct as well as the
      previously suggested 2-2'-adduct without a cyclobutane ring are formed upon UV
      irradiation. Evidence for an oxetane-like photoproduct was not found. Different
      time constants for the increase of the product bands were observed. The
      cycloadduct accumulates with a shorter time constant (tau = 2 to 5 min) than the
      2-2'-adduct (tau = 75 min). The yield of the photo-cross-linking reaction was
      determined by spectral deconvolution and kinetic fitting of several marker bands.
      For the copolyimide synthesized in this work, a maximum value of 6% was reached.
      The stiffness of the copolyimide backbone inhibits further photo-cross-linking.

PMID- 22366817
TI  - 18F-fluoride PET/CT for bone scanning. Role of attenuation correction.
AB  - AIM: 18F-fluoride PET/CT is a promising tool for bone scanning. Recently,
      guidelines concerning the conduct of 18F-fluoride PET/CT have been published. One
      open question of the German guideline was the necessity of attenuation correction
      for 18F-fluoride PET/CT. We evaluated the need for a CT-based attenuation
      correction in 18F-fluoride PET/CT scans for the detection of bone lesions.
      PATIENTS AND METHODS: We retrospectively analyzed whole-body 18F-Fluoride PET/CT
      scans of 59 cancer patients. The lesions were categorized as malignant, benign or
      inconclusive. This assignment was performed for every lesion in both: attenuation
      corrected (AC) and non-attenuation-corrected (NAC) images. The maximum
      standardized uptake values (SUVmax) of the lesion in the AC images were also
      determined. RESULTS: All bone lesions were detected in both image modalities. The
      AC images revealed 201 lesions categorized as malignant, 114 as benign and 35 as
      inconclusive. Without an AC, the results were 209, 116 and 25, respectively (p >
      0.05). 10/35 lesions categorized as inconclusive in the AC images were
      categorized as malignant in the NAC images, whereas 8 lesions were confirmed
      after comparison with other imaging modalities and follow-up data and 2 lesions
      were categorized as benign. The SUVmax for lesions identified as malignant showed
      a broad overlap with the SUV max of benign lesions and can consequently not be
      used for differentiation. CONCLUSION: An AC is not necessary for detecting bone
      lesions on 18F-fluoride PET/CT scans as the detection capability is identical for
      NAC imaging and lesion assignment was even better than with AC imaging. SUVmax
      seems not to improve the differentiation between malignant and benign bone
      lesions.

PMID- 22366818
TI  - Magnetic nanoparticles: an improved method for mitochondrial isolation.
AB  - The ultrastructure, function, and physical and chemical properties of
      mitochondria have become important issues in scientific research. Current
      mitochondrial isolation methods mainly rely on the physical and chemical
      properties of mitochondria. Our team presents a fast and reliable new isolation
      method based on magnetic nanoparticles binding with monoamine oxidase-A (MAO-A)
      expressed in the mitochondria. MAO-A is expressed in the outer membrane of human
      mitochondria and is localized on the cytoplasmic side of the membrane, which
      makes it possible to isolate the mitochondria effectively, using a magnetic
      field. As shown in the present study, in comparison with differential
      centrifugation and density gradient centrifugation, the yield of mitochondria
      isolated by magnetic nanoparticle binding is higher, with greater mitochondrial
      purity and activity. The entire process, from cell harvesting to final isolation
      of the mitochondria, takes approximately 1 h. Magnetic nanoparticles provide a
      simple, practical approach for mitochondrial isolation.

PMID- 22366819
TI  - Pleiotropic effects of dronedarone on ischemia/reperfusion injury in heart and
      brain.
AB  - In the present manuscript we critically review the available evidence for
      pleiotropic effects of dronedarone in settings of myocardial and cerebral
      ischemia/reperfusion, both from experimental and clinical data.

PMID- 22366821
TI  - Stroke rehabilitation is associated with a reduction in dementia risk: a
      population-based retrospective cohort study.
AB  - OBJECTIVE: Focusing on the relationship between physical activity and incident
      cognitive impairment, the aim of this study was to investigate whether stroke
      rehabilitation reduces the risk of dementia. METHODS: Claims data of 1,000,000
      insured subjects randomly selected from the National Health Insurance programme
      of Taiwan were used to identify adults with a newly diagnosed ischaemic stroke in
      1997-2002. Among them, 1,375 received rehabilitation and 3,722 did not. Both
      groups were followed up until the end of 2007 to measure the incidence of
      development of dementia. RESULTS: The incidence of development of dementia was
      lower in the rehabilitation cohort than in the non-rehabilitation cohort (1.22 vs
      1.70 per 100 person-years), with an adjusted hazard ratio (HR) of 0.73 (95%
      confidence interval (CI) = 0.60-0.89) in the multivariate Cox proportional hazard
      regression analysis. Female gender (HR = 1.26, 95% CI = 1.07-1.50), older age (HR
      = 7.71, 95% CI = 3.36-17.7), low income (HR = 1.82, 95% CI = 1.42-2.33), and
      Parkinson's disease (HR = 1.64, 95% CI = 1.33-2.03) were risk factors associated
      with the development of dementia. CONCLUSION: Post-stroke rehabilitation is
      associated with a reduction in dementia risk among ischaemic stroke patients.

PMID- 22366820
TI  - Mammalian-transmissible H5N1 influenza: facts and perspective.
AB  - Two recently submitted (but as yet unpublished) studies describe success in
      creating mutant isolates of H5N1 influenza A virus that can be transmitted via
      the respiratory route between ferrets; concern has been raised regarding human-to
      human transmissibility of these or similar laboratory-generated influenza
      viruses. Furthermore, the potential release of methods used in these studies has
      engendered a great deal of controversy around publishing potential dual-use data
      and also has served as a catalyst for debates around the true case-fatality rate
      of H5N1 influenza and the capability of influenza vaccines and antivirals to
      impact any future unintentional or intentional release of H5N1 virus. In this
      report, we review available seroepidemiology data for H5N1 infection and discuss
      how case-finding strategies may influence the overall case-fatality rate reported
      by the WHO. We also provide information supporting the position that if an H5N1
      influenza pandemic occurred, available medical countermeasures would have limited
      impact on the associated morbidity and mortality.

PMID- 22366822
TI  - The future of health care delivery and the experience of a tertiary care center
      in Saudi Arabia.
AB  - Five major technological changes will herald a new era in health care delivery
      around the World: digitalization of the personal health record, sharing of health
      care digital data across different platforms, applications and institutions,
      delivery of patient services via the internet, use of the digital media and
      social networking as a medium for education and preventive medicine and
      introduction of smart applications as counselors to prevent medical errors. The
      implications of such changes are huge. Saudi Arabia is not isolated from such
      important developments. This article explores the future of health care delivery
      with a special focus on the experience of a tertiary care center in Saudi Arabia
      that has led the wave in such changes regionally.

PMID- 22366823
TI  - Association of genetic polymorphisms of glutamate decarboxylase 2 and the
      dopamine D2 receptor with obesity in Taiwanese subjects.
AB  - BACKGROUND AND OBJECTIVES: It has been proposed that glutamate decarboxylase 2
      and the dopamine D2 receptor are involved in the brain reward cascade to increase
      carbohydrate craving and cause eating disorders. We investigated the association
      between the polymorphisms of the GAD2 and DRD2 genes and obesity with a higher
      body mass index (BMI) in Taiwanese patients. DESIGN AND SETTING: A retrospective,
      case-control study at Antai Tian-Sheng Memorial Hospital from 1 January to 31
      December 2009. SUBJECTS AND METHODS: Of 300 subjects enrolled in the study, 132
      were obese (BMI>=30 kg/m2) and 168 controls were not obese (BMI<=24 kg/m2). The
      polymorphisms of GAD2 (+61450 C/A), (+83987 T/A) and DRD2 (S311C) were
      characterized, respectively, by polymerase chain reaction-restriction fragment
      length polymorphism. The genotype and allele frequencies of the polymorphisms in
      this study were statistically analyzed. RESULTS: The genotype and allele
      frequencies of the GAD2 (+83987 T/A) and DRD2 (S311C) were significantly
      different between cases and controls (P=.001 for both). The frequencies of TT
      genotype and T allele of the GAD2 (+83987 T/A) as well as the frequencies of
      Ser/Cys genotype and Cys allele of DRD2 (S311C) were higher in cases compared to
      controls (P=.034 and =.036 for both). CONCLUSIONS: The study demonstrated a
      statistically significant difference in the frequency of the GAD2 (+83987 T/A)
      and DRD2 (S311C) genes between cases and controls in Taiwanese subjects.

PMID- 22366824
TI  - Association of interleukin-4 polymorphisms with multiple sclerosis in
      southeastern Iranian patients.
AB  - BACKGROUND AND OBJECTIVES: Immune system-related factors are important in the
      pathogenesis of multiple sclerosis (MS). Interleukin 4 (IL-4) as a helper T cell
      (2TH) cytokine is involved in the regulation of immune responses. Hence, this
      study was designed to explore the association between MS and polymorphisms in the
      -590 region of IL-4. DESIGN AND SETTING: A descriptive study at Rafsanjan
      University of Medical Sciences, Rafsnajan from September 2009 to August 2010.
      PATIENTS AND METHODS: Blood samples were collected from 100 MS patients and 150
      healthy controls on EDTA precoated tubes. DNA was extracted and analyzed for IL-4
      polymorphisms using restricted fragment length polymorphism in patients and
      controls. Demographic data were also collected by a questionnaire that was
      designed specifically for this study. RESULTS: We observed a significant
      difference in the C/C, T/C, and T/T genotypes of the -590 region of IL-4 between
      patients with MS and healthy controls (P<.001). CONCLUSIONS: We conclude that
      functional polymorphisms of IL-4 possibly play a crucial role in the pathogenesis
      of MS.

PMID- 22366825
TI  - Safety of recombinant human deoxyribonuclease as a rescue treatment for
      persistent atelectasis in newborns.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary problems are vitally important in newborns.
      Increased intense and mucoid secretions may lead to atelectasis, pulmonary
      infections, respiratory distress, prolonged mechanical ventilation or even death.
      The aim of this study was to evaluate the safety of recombinant human
      deoxyribonuclease (rhDNase) in the management of persistent atelectasis in term
      and preterm newborns, unresponsive to the conventional treatment. DESIGN AND
      SETTING: Prospective study of patients admitted to a general community setting of
      a neonatal intensive care unit between December 2007 and December 2009. PATIENTS
      AND METHODS: The study included 22 patients (12 premature and 10 term) who were
      admitted to the neonatal intensive care unit because of respiratory distress and
      developed atelectasis, and were unresponsive to conventional treatment. Nebulized
      rhDNase was administered to all patients at a dose of 1 mg/m2 twice daily for 3
      days. In patients who did not respond to 3 days of treatment, endotracheal
      rhDNase was administered at a dose of 1 mg/m2. We assessed the clinical
      (respiratory rate and oxygen requirement) and radiologic responses (chest
      radiographic score), recurrence of atelectasis, the need for a repetitive
      treatment, and mortality rate. RESULTS: A clinical and radiologic improvement of
      atelectasis was observed in 18 of 22 patients following 3 days of nebulized
      rhDNase treatment. Atelectasis relapsed in 4 patients. Following the
      administration of combined endotracheal and nebulized rhDNase treatment, an
      improvement of atelectasis was noted in all four recurrent cases. No adverse
      events were observed in patients because of the rhDNase treatment. CONCLUSIONS:
      rhDNase treatment is a safe option and may be used as an effective method for the
      management of persistent atelectasis in newborns, which is resistant to other
      conventional treatment methods.

PMID- 22366826
TI  - Fine needle aspiration cytology in the evaluation of lymphoid lesions: a
      retrospective study of the utility of flow cytometry in conjunction with
      morphology.
AB  - BACKGROUND AND OBJECTIVE: Fine needle aspiration (FNA) cytology, in conjunction
      with flow cytometry, is now widely used as a reliable and accurate method for the
      assessment of various lymphoid lesions, especially for lesions situated in odd
      locations where obtaining biopsy and monitoring for recurrence in previously
      diagnosed cases of lymphoma are difficult. The objective of this study was to
      determine the utility of FNA and immunophenotyping in the assessment of lymphoid
      lesions, and to find whether flow cytometry is more useful in the evaluation and
      subclassification of the small cell morphology group of lymphomas than in the
      large cell morphology group of lymphomas. DESIGN AND SETTING: Retrospective
      analysis of patients diagnosed with lymphoma over at a 5-year period. PATIENTS
      AND METHODS: All 175 FNA cases were followed carefully either clinically or
      histologically for at least 5 years. We compared the utility of flow cytometry in
      the diagnosis of small cell morphology lymphomas to large cell morphology
      lymphomas. RESULTS: Flow cytometry was performed on 72 of 175 (41%) of FNA
      specimens clinically suspicious of lymphoma. The excisional follow-up biopsy was
      obtained in 78 of 175 (44.5%) cases. Based on cytomorphologic evaluation, 82
      cases (47%) were considered negative, 34 cases (19%) were considered atypical, 32
      cases (18%) were positive for NHL-small cell morphology, 21 cases (12%) were
      positive for non-Hodgkin lymphoma (NHL)-large cell morphology, 3 cases (2%) were
      positive for NHL, and 3 cases (2%) were nondiagnostic. Immunophenotyping
      utilizing flow cytometry was the diagnostic parameter in 28 of 32 cases (88%) of
      the NHL-small cell morphology group and in 11 of 24 cases (46%) of the NHL-large
      cell morphology/Hodgkin lymphoma group. CONCLUSIONS: Immunophenotyping by flow
      cytometry is more essential for the accurate evaluation and classification of
      small cell morphology than large cell morphology lymphoid lesions in FNA
      cytology.

PMID- 22366827
TI  - Benchmarking the post-accreditation patient safety culture at King Abdulaziz
      University Hospital.
AB  - BACKGROUND AND OBJECTIVES: Accreditation is an internationally recognized
      evaluation process used to assess, promote, and guarantee efficient and effective
      patient care and safety. Saudi Arabia is one of the first countries in the
      eastern Mediterranean region to implement health care accreditation standards.
      This study provides valuable information pertaining to the impact of
      accreditation in the unique multicultural, multilingual competitive environment
      at King Abdulaziz University Hospital in Saudi Arabia. The objective of this
      study was to perform an unbiased assessment of the impact of accreditation on
      patient safety culture. DESIGN AND SETTING: Cross-sectional retrospective and
      prospective study post-accreditation at King Abdulaziz University Hospital in
      Jeddah, Saudi Arabia from January 1, 2006 to December 31, 2009. PATIENTS AND
      METHODS: A total of 870 registered nurses from eight different cultural
      backgrounds working at 22 hospital units were given electronic access to the
      survey. A 5-point Likert scale was used, ranging from 1 for 'Strongly disagree'
      to 5 for 'Strongly agree.' The survey results were matched with the international
      benchmarks from the Hospital Survey on Patient Safety Culture, 2005. RESULTS: A
      total of 605 nurses answered the survey questionnaire. The comparison between the
      percentages of nurses at King Abdulaziz University Hospital (KAUH) and those at
      international hospitals who answered 'Agree' and 'Strongly agree' showed a post
      accreditation improved perception of the culture of patient safety. CONCLUSIONS:
      Accreditation has an overall statistically significant improvement in the
      perception of the culture of patient safety.

PMID- 22366828
TI  - Assessing knowledge of the patient bill of rights in central Saudi Arabia: a
      survey of primary health care providers and recipients.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the implementation of the
      patient bill of rights (PBR) in Saudi Arabia. Therefore, this study was conducted
      to explore to what extent health care recipients and providers know about the
      bill and its implementation. DESIGN AND SETTING: A cross-sectional survey
      conducted on health care professionals and patients at Primary Health Care
      Centers in Riyadh, Saudi Arabia, during July 2010. PATIENTS AND METHODS: The
      study employed a self-administered questionnaire to collect data from 500
      patients (aged 18 years or older) and 500 health care providers (physicians and
      nurses) in primary health care (PHC) centers in Riyadh. Data was collected on the
      respondents' knowledge of the existence and contents of the bill, the extent to
      which the bill is implemented, and the obstacles that may hinder bill
      implementation. The data was analyzed and presented in a descriptive fashion.
      RESULTS: More than three quarters of patients and one third of PHC providers did
      not know about the existence of the bill. Among those who knew about its
      existence, about three quarters of patients and almost half of PHC providers had
      little (or very little) knowledge about the bill contents. In general, patients
      scored lower means of perception than PHC staff about the implementation of the
      bill's aspects. PHC staff reported several obstacles that may hinder the
      implementation of the PBR in Saudi Arabia. CONCLUSIONS: Patients and health care
      providers lack necessary knowledge about the PBR. More dissemination of
      information about the bill, taking into account the particularities of the Saudi
      population is needed. Future research is required to establish measures that are
      effective in ensuring that patients rights are ensured.

PMID- 22366829
TI  - Surgery for chronic total occlusion of the left main coronary artery.
AB  - BACKGROUND AND OBJECTIVES: Chronic total occlusion of the left main coronary
      artery (LMCA) is a rare condition, and the information on surgical experiences is
      limited. Although total occlusion of the LMCA is accompanied by well-developed
      collateral circulation, the condition of circulation is unstable during
      manipulation of the heart. We report our experience with revascularization in
      cases with total occlusion of the LMCA using the on-pump beating-heart (OnP-BH)
      technique. DESIGN AND SETTING: Retrospective case review of patients treated at
      The First Affiliated Hospital of China Medical University over a 10-year period
      (1999 to 2009). PATIENTS AND METHODS: The on-pump coronary artery bypass grafting
      with the beating heart was applied to 8 patients with chronic total occlusion of
      the LMCA. The extracorporeal circulation period, intubation duration, intensive
      care unit stay period, discharge period, preoperative and postoperative
      treatments, and follow-up were observed. RESULTS: The mean extracorporeal
      circulation period was 80.4 (19.7) minutes. The mean intubation duration was 13.0
      (4.6) hours. The mean intensive care unit stay period was 3.2 (0.7) days, and the
      mean discharge period was 16.8 (3.3) days. No perioperative myocardial infarction
      occurred. The mean follow-up period was 50.9 (34.8) months. All patients were
      asymptomatic, and no deaths were recorded during the follow-up period. The
      results of echocardiography showed improvement in the left ventricular function.
      CONCLUSIONS: The OnP-BH myocardial revascularization seems to be a valid
      alternative for chronic total occlusion of the LMCA.

PMID- 22366830
TI  - In vitro-activated tumor-bearing host T cells and the effectiveness of tumor
      vaccine immunotherapy.
AB  - BACKGROUND AND OBJECTIVE: Vaccination during periods of lymphopenia may
      facilitate immune responses to weak self-antigens and enhance antitumor immunity.
      The objective of this study was to determine the effectiveness of tumor vaccine
      immunotherapy combined with immune reconstruction using tumor-bearing host immune
      cells in lymphopenia, and to investigate the role of tumor-bearing host T cells
      activated in vitro during immunotherapy. DESIGN AND SETTING: Animal study
      conducted in the First Affiliated Hospital of Xi'an Jiaotong University from
      January 2009 to January 2010. PATIENTS AND METHODS: Lymphopenia was induced by
      cyclophosphamide. A reconstituted immune system with different syngeneic
      lymphocytes was employed, including lymphocytes from naive rats (unsensitized
      group), tumor-bearing rats (tumor-bearing group), and tumor-bearing rats
      activated in vitro (activated group). All rats were immunized with granulocyte
      macrophage colony-stimulating factor (GM-CSF)-modified NuTu-19 ovarian cancer (GM
      CSF/NuTu-19) cells. Tumor vaccine-draining lymph nodes (TVDLNs) were harvested,
      and then stimulated to induce effector T cells (T(E)). T(E) were then adoptively
      transferred to rats bearing a 3-day pre-established abdominal tumor (NuTu-19),
      and the survival rate was calculated. RESULTS: Compared with the unsensitized
      group, the levels of interleukin-2 (IL-2) were significantly lower in the tumor
      bearing group, whereas that of IL-4 were significantly higher (P<.05). The number
      of CD4+ T cells secreting interferon-gamma and the specific cytotoxicity of CD8+
      cytotoxic T lymphocytes were significantly lower (P<.05). The survival was
      significantly higher in the activated group compared with the other groups.
      CONCLUSIONS: Lymphocytes from tumor-bearing rats activated in vitro can
      effectively reverse the immunosuppressive effects of tumor-bearing hosts.

PMID- 22366831
TI  - Peripherally inserted central catheter bloodstream infection surveillance rates
      in an acute care setting in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVE: Peripherally inserted central venous catheters (PICCs)
      are alternatives to short-term central venous catheters and provide intravenous
      access in the acute hospital setting. In this study, we describe the rate of PICC
      associated bloodstream infections (BSI). DESIGN AND SETTING: Prospective cohort
      study using data on PICC lines reviewed from January to December 2009. METHODS:
      The infection control team was responsible for prospective BSI case findings. The
      infection rate was calculated per 1000 device-days. RESULTS: During the study
      period, 92 PICC lines were inserted with a total of 3336 device-days of
      prospective surveillance. The most frequent reasons for the insertion of the PICC
      lines were chemotherapy (n=19, 20.7%), intravenous antimicrobial therapy (n=34,
      37%), and for patients in the medical intensive care unit (ICU) (n=16, 17.4%).
      The overall BSI rate was 4.5/1000 PICC days. The PICC line-associated BSI rates
      for a specific indication were as follows: chemotherapy 6.6/1000 device-days,
      intravenous antimicrobial therapy 1.2/1000 device-days, medical ICU 7.3/1000
      device-days, surgical ICU 4.6/1000 device-days, and total parental nutrition
      patients 2.4/1000 device-days (P<.001). The rates were not adjusted for patient
      severity of illness. CONCLUSIONS: Our data suggest that underlying conditions and
      indications for the PICC line use may play an important role in the development
      of BSI.

PMID- 22366833
TI  - Prevalence of hepatitis C virus infection and human immunodeficiency virus in a
      cohort of Egyptian hemophiliac children.
AB  - BACKGROUND AND OBJECTIVE: The risk of blood-borne infections, especially
      hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection still
      remains in developing countries among children receiving blood products as
      hemophiliacs, but the risk is not known in Egypt. The objective of this study was
      to detect the prevalence of HCV and HIV infection among hemophiliac children to
      know the magnitude of the problem and determine potential risk factors. PATIENTS
      AND METHODS: This was a cross-sectional study conducted on 100 hemophiliac
      children that assessed the liver clinically and by laboratory tests. All children
      were screened for HCV and HIV antibodies by enzyme-linked immunosorbent assay.
      Those with positive HCV antibody titre were tested by polymerase chain reaction
      (HCV-PCR). RESULTS: Forty were positive for HCV antibodies with 19 children
      (47.5%) HCV-PCR positive as well. The mean age, average frequency of bleeds/year,
      dose of replacement therapy/year and alanine aminotransferase (ALT) levels were
      significantly high in HCV-antibody and PCR positive patients as compared to HCV
      antibody and PCR negative ones. None of our patients had clinical evidence of
      hepatic involvement or was co-infected with HIV. CONCLUSION: HIV infection does
      not appear to be a current health problem in Egyptian hemophiliac children though
      the prevalence of HCV infection is still high.

PMID- 22366834
TI  - Undifferentiated sarcoma of the liver: a rare pediatric tumor.
AB  - Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic
      tumor of mesenchymal origin recognized as a unique clinicopathologic entity since
      1978. UESL has historically been considered an aggressive neoplasm with an
      unfavorable prognosis. Survival has improved using recent multimodal approaches,
      designed for patients with soft tissue sarcomas at other sites. Several small
      series have reported survival of up to 70% of children. We report a case of a 12
      year-old boy from the United Arab Emirates who relapsed after complete surgical
      resection and was then successfully treated with re-resection followed by
      chemotherapy and radiotherapy. With a follow-up of 5 years, he is well and
      asymptomatic, and is leading a healthy life. This case emphasizes the fact that
      these poorly prognostic tumors may benefit from post-surgery chemotherapy. This
      case illustrates the improved survival of UESL patients following the
      multimodality therapy with a relatively long follow-up. This is the first case of
      UESL reported in this region of the world.

PMID- 22366835
TI  - Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis
      syndrome: a rare cause of protein-losing enteropathy.
AB  - Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease.
      Typically, ISH patients present with progressive painful joint contractures,
      intractable diarrhea, hyperpigmented skin lesions, and peri-anal fleshy nodules.
      We report a case of a 19-month-old male child with atypical ISH presentation. His
      main clinical finding was protein-losing enteropathy due to intestinal
      lymphangectasia. This report is intended to enhance awareness about the
      gastrointestinal tract presentation of ISH.

PMID- 22366836
TI  - Low-grade malignant myoepithelioma arising in a pleomorphic adenoma: a rare case.
AB  - Malignant myoepithelioma is a very rare salivary gland tumor that can arise de
      novo or within a pre-existing pleomorphic adenoma. We report a case of malignant
      myoepithelioma most probably arising in a pre-existing pleomorphic adenoma of the
      left parotid gland. The patient was a 60-year-old man who presented with a
      multinodular mass lesion over left side of the face and neck. He had undergone
      removal of a pleomorphic adenoma of the left parotid gland twice (8 and 22 years
      ago). Histological examination showed locally concentrated highly invasive
      myoepithelial cells with bland-looking morphology and no evidence of mitosis or
      necrosis. Immunohistochemistry confirmed the myoepithelial differentiation (S-
      100+, SMA+) and a low Ki-67 labeling index (<5%).

PMID- 22366832
TI  - Saudi guidelines for the diagnosis and management of hepatocellular carcinoma:
      technical review and practice guidelines.
AB  - Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi
      Arabia, and the difficulties often faced in early and accurate diagnoses,
      evidence-based management, and the need for appropriate referral of HCC patients,
      the Saudi Association for the Study of Liver diseases and Transplantation (SASLT)
      formed a multi-disciplinary task force to evaluate and update the previously
      published guidelines by the Saudi Gastroenterology Association. These guidelines
      were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as
      its official HCC guidelines as well. The committee assigned to revise the Saudi
      HCC guidelines was composed of hepatologists, oncologists, liver surgeons,
      transplant surgeons, and interventional radiologists. Two members of the task
      force served as guidelines editors. A wide based search on all published reports
      on all aspects of the epidemiology, natural history, risk factors, diagnosis, and
      management of HCC was performed. All available literature was critically examined
      and available evidence was then classified according to its strength. The whole
      document and the recommendations were then discussed in detail by members and
      consensus was obtained. All recommendations in these guidelines were based on the
      best available evidence, but were tailored to the patients treated in Saudi
      Arabia. We hope that these guidelines will improve HCC patient care and enhance
      the multidisciplinary care needed for these patients.

PMID- 22366837
TI  - RE: Reported child sexual abuse in Bahrain: 2000- 2009.

PMID- 22366838
TI  - Response to comments on urine iodine excretion in patients with euthyroid nodular
      disease.

PMID- 22366840
TI  - RE: Antenatal screening for Toxoplasma gondii infection at a tertiary care
      hospital in Riyadh, Saudi Arabia.

PMID- 22366842
TI  - Computed tomography-estimated specific gravity at hospital admission predicts 6
      month outcome in mild-to-moderate traumatic brain injury patients admitted to the
      intensive care unit.
AB  - BACKGROUND: It is clear that patients with a severe traumatic brain injury (TBI)
      develop secondary, potentially lethal neurological deterioration. However, it is
      difficult to predict which patients with mild-to-moderate TBI (MM-TBI), even
      after intensive care unit (ICU) admission, will experience poor outcome at 6
      months. Standard computed tomography (CT) imaging scans provide information that
      can be used to estimate specific gravity (eSG). We have previously demonstrated
      that higher eSG measurements in the standard CT reading were associated with poor
      outcomes after severe TBI. The aim of this study was to determine whether eSG of
      the intracranial content predicts 6-month outcome in MM-TBI. METHODS: We analyzed
      admission clinical and CT scan data (including eSG) of 66 patients with MM-TBI
      subsequently admitted to our neurosurgical ICU. Primary outcome was defined as a
      Glasgow Outcome Scale score of 1 to 3 after 6 months. Discriminating power (area
      under the receiver operating characteristic curve [ROC-AUC], 95% confidence
      interval) of eSG to predict 6-month poor outcome was calculated. The correlation
      of eSG with the main ICU characteristics was then compared. RESULTS: Univariate
      and stepwise multivariate analyses showed an independent association between eSG
      and 6-month poor outcome (P = 0.001). ROC-AUC of eSG for the prediction of 6
      month outcomes was 0.87 (confidence interval: 0.77-0.96). Admission eSG values
      were correlated with the main ICU characteristics, specifically 14-day mortality
      (P = 0.004), length of mechanical ventilation (P = 0.01), length of ICU stay (P =
      0.045), and ICU procedures such as intracranial pressure monitoring (P < 0.001).
      CONCLUSIONS: In this MM-TBI cohort admitted to the ICU, eSG of routine CT scans
      was correlated with mortality, ICU severity, and predicted 6-month poor outcome.
      An external validation with studies that include the spectrum of TBI severities
      is warranted to confirm our results.

PMID- 22366843
TI  - Ultrasound-guided popliteal sciatic block with a single injection at the sciatic
      division results in faster block onset than the classical nerve stimulator
      technique.
AB  - BACKGROUND: For successful, fast-onset sciatic popliteal block (SPB), either a
      single injection above the division of the sciatic nerve, or 2 injections to
      block the tibial nerve (TN) and common peroneal nerve (CPN) separately have been
      recommended. In this study, we compared the traditional nerve stimulator (NS)
      guided SPB above the division of the sciatic nerve with the ultrasound (US)
      guided block with single injection of local anesthetic (LA) between the TN and
      CPN at the level of their division. We hypothesized that US-SPB with a single
      injection between TN and CPN would result in faster block onset than a single
      injection NS-SPB. METHODS: Fifty-two patients were randomized to receive either
      an NS-SPB or a US-SPB. For both blocks, a single injection of 20 mL mepivacaine
      1.5% was given using an automated injection pump while controlling for injection
      force. For NS-SPB, a TN response below 0.5 mA was sought 7 cm above the popliteal
      fossa crease (and proximal to the divergence of the TN and peroneal nerves). For
      US-SPB, the injection was made after a US-guided needle was inserted between the
      TN and CPN at the level of their separation. Motor response was not actively
      sought but registered if present. The location and spread of LA were evaluated by
      US in both groups. Onset of motor and sensory blocks was serially assessed in 5
      minute intervals in the TN and CPN divisions and compared between the groups.
      RESULTS: All patients in both groups had successful block at 30 minutes after the
      injection, defined as sensory block to allow surgery without supplementation. A
      higher proportion of patients in the US-SPB group had a complete sensory (80% vs
      4%, P < 0.001) and motor block (60% vs 8%, P < 0.001), defined as anesthesia and
      paralysis in all nerve territories, at 15 minutes after injection. US signs of
      intraepineural injection were present in 19 patients (73%) in the NS-SPB group
      and 25 patients (100%) in the US-SPB group (P < 0.001). CONCLUSIONS: A single
      injection of LA in US-SPB with needle insertion at the separation of the TN and
      CPN results in a similar success rate at 30 minutes; however, more patients in
      the US-SPB group than in the NS-SPB group had complete block at 15 minutes.

PMID- 22366844
TI  - Anesthesiology residents' medical school debt influence on moonlighting
      activities, work environment choice, and debt repayment programs: a nationwide
      survey.
AB  - BACKGROUND: The amount of education debt incurred by medical school graduates in
      the United States has grown considerably over the last 30 years; it has outpaced
      inflation to reach a mean of $158,000. With this dramatic increase in education
      debt, there has been limited information on how medical school debt loads of
      anesthesiology physicians impact their decisions concerning moonlighting and
      future career choices. Our aim was to survey current anesthesiology interns,
      residents, and fellows to assess the correlation between the amount of medical
      school debt they had collected and (1) their outlook toward moonlighting
      activities, (2) future career plans, and (3) choice of employer with a debt
      repayment program. METHODS: We developed a web-based survey instrument and
      contacted residency training programs to obtain access to their anesthesiology
      interns, residents, and fellows (residents). We assessed each relationship of
      interest using a multivariable proportional odds model, adjusting for all
      available baseline potential confounding factors. Second, we compared
      participants with >$150,000 medical school debt versus participants with no debt
      on the same questions of interest, each using a multivariable proportional odds
      model with the same covariable adjustment. RESULTS: We had access to 2386
      residents through their training programs and 537 completed the survey. Those
      respondents with a 1-category-larger amount of medical school debt (i.e.,
      $30,000) were associated with 7%(99.3% confidence interval: 0%, 13%) increased
      odds of having the desire to moonlight during residency/fellowship, and were
      associated with 7% (1%, 13%) decreased odds of saying they would choose a career
      as an academic faculty, respectively. Also, those with a larger amount of medical
      school debt were more likely to be swayed to be interested in an anesthesiology
      group with an education debt repayment program (odds ratio: 1.3 [1.22, 1.39] for
      1-category increase in the debt amount); furthermore, the corresponding odds
      ratio was increased to 4.6 (2.8, 7.5) comparing those with >$150,000 debt with
      those without debt. CONCLUSIONS: In an effort to compete with private practice
      anesthesiology groups and to reduce the impact of debt on future career choices
      of residents/fellows, academic anesthesiology groups would do well to (1) promote
      moonlighting activities that are within the Accreditation Council for Graduate
      Medical Education and institutional guidelines, (2) develop financial curriculum
      for residents/fellows, and (3) offer debt repayment programs as an incentive for
      new faculty to join academic medicine.

PMID- 22366845
TI  - Unplanned endotracheal extubations in the intensive care unit: systematic review,
      critical appraisal, and evidence-based recommendations.
AB  - BACKGROUND: In this study, we updated the state of knowledge on unplanned
      tracheal extubations in the intensive care unit. We focused on the following
      topics: incidence, risk factors, reintubation after unplanned extubation,
      outcomes, and prevention. Based on this review, recommendations were made for
      preventing unplanned extubations. METHODS: Electronic databases were searched for
      relevant publications from January 1, 1950 through June 30, 2011 on the MEDLINE,
      EMBASE, CINAHL, SciELO, LILACS, and Cochrane systems. Fifty articles were
      eligible for data abstraction. Study quality was assessed using the Newcastle
      Ottawa Scale. Grades of recommendation were assessed according to the Oxford
      Centre for Evidence-Based Medicine. RESULTS: Unplanned extubations occur at a
      rate of 0.1 to 3.6 events per 100 intubation days. Risk factors associated with
      unplanned extubations included male gender (odds ratio [OR] 4.8), APACHE score
      >=17 (OR 9.0), chronic obstructive pulmonary disease, restlessness/agitation (OR
      3.3-30.6), lower sedation level (OR 2.0-5.4), higher consciousness level (OR 1.4
      2.0), and use of physical restraints (OR 3.1). Reintubation rates ranged from
      1.8% to 88% of unplanned extubations. Thirteen studies assessed preventive
      measures for avoiding unplanned extubations. These studies focused on data
      collection tools, standardization of procedures, staff education, staff
      surveillance, and identification and management of high-risk patients. These
      studies reported reductions in unplanned extubation rate from 22% to 53%. The
      best methods of securing the endotracheal tube and use of physical restraints
      remain controversial issues. CONCLUSIONS: Despite numerous publications on
      unplanned extubation, few studies assess preventive strategies for adverse
      events, and few clinical trials have assessed unplanned extubations.
      Recommendations are proposed based on the currently available literature.

PMID- 22366846
TI  - Nimodipine-induced hypotension but not nitroglycerin-induced hypotension
      preserves long- and short-term memory in adult mice.
AB  - BACKGROUND: Acute hypotension may be implicated in cognitive dysfunction. L-type
      calcium channel blockers in the setting of hypoxia are protective of learning and
      memory. We tested the hypothesis that hypotension induced by nimodipine (NIMO)
      and nicardipine (NICA) would be protective of long- and short-term memory
      compared to hypotension induced by nitroglycerin (NTG). METHODS: Forty Swiss
      Webster mice (30 to 35 g, 6 to 8 weeks) were randomized into 4 groups for i.p.
      injection immediately after passive avoidance (PA) learning on day 0: (1) NTG (30
      mg/kg); (2) NICA (40 mg/kg); (3) NIMO (40 mg/kg); and (4) saline. PA training
      latencies (seconds) were recorded for entry from a suspended platform into a
      Plexiglas tube where a shock (0.3 mA; 2-second duration) was automatically
      delivered. On day 2 latencies were recorded during a testing trial during which
      no shock was delivered. Latencies >900 seconds were assigned this value. Lower
      testing latency is indicative of an impairment of long-term associative memory.
      Forty-nine additional mice were randomized into similar groups for object
      recognition testing (ORT) and given i.p. injections on day 0. ORT measures short
      term memory by exploiting the tendency of mice to prefer novel objects where a
      familiar object is present. On day 5 during training, 2 identical objects were
      placed in a circular arena and mice explored both for 15 minutes. A testing trial
      was conducted 1 hour later for 3 minutes after a novel object replaced a familiar
      one. Mice with intact memory spend about 65% of the time exploring the novel
      object. Mice with impaired memory devote equal time to each object. Recognition
      index (RI) is defined as the ratio of time spent exploring the novel object to
      time spent exploring both objects was the measure of memory. Mean arterial blood
      pressure (MAP), cerebral bloodflow, and body and brain oxygenation (PO(2))
      studies were done in separate groups of mice to determine the dosages for matched
      degrees of hypotension and the physiological profile of each treatment. RESULTS:
      The median PA latencies for the different conditions were as follows: NTG (219.5
      +/- 93.5 second semi-interquartile range [SIQR]), NICA (372.5 +/- 75.5 second
      SIQR), NIMO (540 +/- 200 second SIQR) and saline (804 +/- 257.5 second SIQR).
      Rank methods were used to analyze the PA latencies for significant differences.
      NTG latency was significantly shorter than NIMO latency (P = 0.012) and saline
      latency (P = 0.006), but not NICA latency (P = 0.126). ORT RI values showed a
      similar pattern. We found that NTG RI (47.2 +/- 5.9% SEM) was different from NIMO
      RI (60.2 +/- 4.6% SEM, P = 0.031) and different from saline RI (66.9 + 3.7% SEM,
      P = 0.006). Physiological experiments showed that MAP decreased to 45 to 50 mm Hg
      in all animals who became minimally responsive to external stimuli within 10 to
      15 minutes of injection. Intergroup differences for MAP, body and brain
      oxygenation, and cerebral bloodflow were not statistically significant.
      CONCLUSION: Acute hypotension induced by NIMO was protective of 2 categories of
      memory formation relevant to the clinical posttreatment period. Both immediate
      long-term associative memory consolidation as measured by the PA learning
      paradigm and delayed short-term working memory function as measured by the ORT
      paradigm were significantly improved compared to matched levels of hypotension
      induced by NTG. These results indicate the utility of further investigation of l
      type calcium channel blockers as a potential means of preserving cognition in the
      setting of hypotensive and low flow states.

PMID- 22366847
TI  - Oxygen desaturation index from nocturnal oximetry: a sensitive and specific tool
      to detect sleep-disordered breathing in surgical patients.
AB  - INTRODUCTION: It is impractical to perform polysomnography (PSG) in all surgical
      patients suspected of having sleep disordered breathing (SDB). We investigated
      the role of nocturnal oximetry in diagnosing SDB in surgical patients. METHOD:
      All patients 18 years and older who visited the preoperative clinics for
      scheduled inpatient surgery were approached for study participation. Patients
      expected to have abnormal electroencephalographic findings were excluded. All
      patients underwent an overnight PSG at home with a portable device and a pulse
      oximeter. The PSG recordings were scored by a certified sleep technologist. The
      oximetry recordings were processed electronically. RESULT: Four hundred seventy
      five patients completed the study: 217 males and 258 females, aged 60 +/- 11
      years, and body mass index 31 +/- 7 kg/m(2). The apnea-hypopnea index (AHI), the
      average number of episodes of apnea and hypopnea per hour of sleep, was 9.1 (2.8
      to 21.4) [median (interquartile range)] and 64% patients had AHI >5. There was a
      significant correlation between oxygen desaturation index (ODI, hourly average
      number of desaturation episodes) and cumulative time percentage with SpO(2) <90%
      (CT90) from nocturnal oximetry, with the parameters measuring sleep breathing
      disorders from PSG. Compared to CT90, ODI had a stronger correlation and was a
      better predictor for AHI. The area under receiver operator characteristics curve
      for ODI to predict AHI >5, AHI >15, and AHI >30 was 0.908 (CI: 0.880 to 0.936),
      0.931 (CI: 0.090 to 0.952), and 0.958 (CI: 0.937 to 0.979), respectively. The
      cutoff value based on the maximal accuracy for ODI to predict AHI >5, AHI >15,
      and AHI >30 was ODI >5, ODI >15, and ODI >30. The accuracy was 86% (CI: 83%-88%),
      86% (CI: 83%-89%), and 94% (CI: 92%-96%), respectively. The ODI >10 demonstrated
      a sensitivity of 93% and a specificity of 75% to detect moderate and severe SDB.
      CONCLUSIONS: ODI from a high-resolution nocturnal oximeter is a sensitive and
      specific tool to detect undiagnosed SDB in surgical patients.

PMID- 22366848
TI  - Accuracy of identification of the cricothyroid membrane in female subjects using
      palpation: an observational study.
AB  - BACKGROUND: The cricothyroid membrane (CTM) is the recommended site of access to
      the airway during cricothyroidotomy to provide emergency oxygenation. Despite the
      apparent simplicity of the technique, this rescue maneuver frequently fails to
      achieve its goals and complications are numerous. The reasons for this failure
      are unclear. We sought to determine the ability of physicians to correctly
      identify the CTM in female patients. METHODS: Using fluorescent "invisible" ink,
      the physician was asked to mark the CTM with the patient in the supine neutral
      position and then with the head extended. The actual level was identified using
      ultrasound and the distance between the actual and estimated margin of the CTM
      was measured. A correct estimation was defined as a mark made between the upper
      and lower limits of the membrane and within 5 mm of midline. Participants were
      also asked to assess the ease of CTM palpation using a 10-cm visual analog
      scoring (VAS) scale. RESULTS: Fifty-six patients participated of whom 15 were
      obese. In the supine neutral neck position, the CTM was identified in 10/41 vs
      0/15 (P = 0.048) in nonobese versus obese, respectively. Of the 46 incorrectly
      identified CTMs in this position, 24 were above (maximum 3 cm) and 22 below
      (maximum 3 cm) the actual level. Similar results were observed when the patients
      were placed with the neck in the extended position; the CTM was identified
      correctly in 12/41 vs 1/15 nonobese and obese patients, respectively. The range
      of values was also extensive; the estimation of the position of the membrane was
      as high as 2.5 cm above and 4 cm below the actual level, and up to 1.6 cm
      laterally. Participating doctors found palpation of the CTM subjectively more
      difficult in the obese than nonobese groups; VAS score for palpation difficulty
      was 5.25 +/- 2.5 vs 3.3 +/- 2.5, respectively, P = 0.005. Using multiple linear
      regression, VAS scores for palpation correlated negatively with increased patient
      height (P < 0.001) and greater thyromental distance (P = 0.006), and correlated
      positively with increased sternomental distance (P = 0.011) and neck
      circumference (P = 0.001). CONCLUSIONS: Misidentification of the CTM in female
      patients is common and its localization is less precise in those who are obese.
      This has implications for the likely success of invasive airway access via the
      CTM.

PMID- 22366849
TI  - Rainy days for the Society for Pediatric Anesthesia.
AB  - Members of the Society for Pediatric Anesthesia (SPA) perceive the 47% rain rate
      has burdened its national meetings more than would be expected. We compared
      weather conditions on the first day of each national SPA meeting since 1987 with
      historical data using the day, month, and location of each meeting. Using a
      generalized estimating equations model, the odds ratio of rain comparing meeting
      and nonmeeting days was 2.63 (P value 0.006, 95% confidence interval 1.32-5.22).
      These results confirm a significantly higher frequency of rain at national SPA
      meetings than would be anticipated.

PMID- 22366850
TI  - Performance validation of a modified magnetic resonance imaging-compatible
      temperature probe in children.
AB  - INTRODUCTION: During magnetic resonance imaging (MRI), children are at risk for
      body temperature variations. The cold MRI environment that preserves the MRI
      magnet can cause serious hypothermia. On the other hand, hyperthermia may also
      develop because of radiofrequency-induced heating of the tissues, particularly in
      prolonged examinations. Because of a lack of MRI-compatible core temperature
      probes, temperature assessment is unreliable, and specific absorption rate
      related patient heat gain must be calculated to determine the allowable scan
      duration. We compared an MRI-compatible temperature probe and a modification
      thereof to a standard esophageal core body temperature probe in children.
      METHODS: Children undergoing general anesthesia were recruited, each patient
      serving as his/her own control. Core body temperature was measured using 3
      different devices: (1) a fiberoptic MRI-compatible skin surface temperature probe
      (MRI-skin) located on the child's skin surface; (2) a fiberoptic MRI-compatible
      temperature probe modified with a single-use sleeve at the tip (MRI-core),
      located in the nasopharynx; and (3) a standard temperature monitor (STRD) located
      in the esophagus or nasopharynx. The Bland-Altman method was used for statistical
      analysis. RESULTS: We enrolled 60 children aged 7.8 +/- 6 years (mean +/- SD)
      weighing 32.4 (+/-26.4) kg. The estimated difference between the STRD and MRI
      core measurements of core temperature was 0.06 degrees C (confidence interval
      [CI]: -0.02, 0.15), and between the STRD and the MRI-skin 1.19 degrees C (CI:
      0.97, 1.41). According to the Bland-Altman analysis, the 95% limits of agreement
      ranged from -0.9 to 3.4 and from -1.3 to 1.2 between the STRD and the MRI-skin
      probe and the MRI-core probe, respectively. DISCUSSION: Our results show good
      agreement between standard esophageal measurements of core temperature and core
      temperature measured using a modified MRI-core probe during general anesthesia in
      a general surgical pediatric population. The ability to accurately assess core
      temperature in the MRI suite may safely allow longer scan times and therefore
      reduce repeat anesthetic exposure, improve patient safety, and enhance the
      quality of care in children.

PMID- 22366851
TI  - Contrast-enhanced ultrasound for myocardial perfusion imaging.
AB  - Ultrasound contrast agents are gas-filled microbubbles that enhance visualization
      of cardiac structures, function and blood flow during contrast-enhanced
      ultrasound (CEUS). An interesting cardiovascular application of CEUS is
      myocardial contrast echocardiography, which allows real-time myocardial perfusion
      imaging. The intraoperative use of this technically challenging imaging method is
      limited at present, although several studies have examined its clinical utility
      during cardiac surgery in the past. In the present review we provide general
      information on the basic principles of CEUS and discuss the methodology and
      technical aspects of myocardial perfusion imaging.

PMID- 22366852
TI  - Historical perspectives of bariatric surgery: the jejunoileal bypass and vertical
      banded gastroplasty.
AB  - While neither the jejunoileal bypass nor vertical banded gastroplasty are still
      performed, many patients still possess this anatomy. They periodically have
      imaging procedures that need to be performed and interpreted appropriately. It is
      also important to know what has failed in the past to proceed more intelligently
      in the future.

PMID- 22366853
TI  - Chronic diverticulitis vs. colorectal cancer: findings on CT colonography.
AB  - PURPOSE: The purpose of this update article is to evaluate findings on CT
      colonography in patients with chronic diverticulitis and to compare the findings
      in patients with colorectal carcinoma. MATERIALS AND METHODS: Different
      morphological criteria retrieved from a literature review were retrospectively
      analyzed in a series of 13 patients with proven chronic diverticulitis. The
      findings were compared with a series of 10 patients with colorectal carcinoma.
      RESULTS: Overall, the findings in chronic diverticulitis resemble the findings in
      acute diverticulitis. The advantage of virtual CT colonography in differentiating
      both entities relies in the combination of morphological features previously
      described on axial computed tomography and double contrast barium enema. The
      single strongest morphological feature pointing towards the diagnosis of chronic
      diverticulitis is the presence of diverticula in the affected segment. In the
      presence of diverticula in the affected segment, a long segment (>=10 cm), thick
      fascia sign without adenopathies, mild bowel wall thickening, tapered margins,
      and distorted but preserved mucosal folds are likely to further improve accuracy
      of diagnosing chronic diverticulitis. CONCLUSION: The single strongest
      morphological sign to differentiate chronic diverticulitis from colorectal cancer
      is the presence of diverticula in the affected segment.

PMID- 22366854
TI  - Aortoenteric fistulas: spectrum of CT findings.
AB  - OBJECTIVE: This article reviews the causes of aortoenteric fistulas, diagnostic
      options, and important CT findings. CONCLUSION: Aortoenteric fistula, a rare but
      potentially fatal entity, presents a significant challenge to radiologists in
      diagnosis, largely because of its subtle and nonspecific imaging findings. These
      fistulas can be divided into primary and secondary forms, depending on the
      presence or absence of prior aortic reconstructive surgery, but the secondary
      form is more common. Typical CT findings, which can overlap with those seen in
      perigraft infection, aortitis, infected/mycotic aneurysms, perianeurysmal
      fibrosis, and the immediate post-operative period after placement of a graft,
      include: Effacement of the fat planes around the aorta, perigraft fluid/soft
      tissue thickening, ectopic gas, tethering of adjacent thickened bowel loops
      towards the aortic graft, and in rare cases, extravasation of contrast from the
      aorta into the involved segment of bowel.

PMID- 22366856
TI  - On not reinventing the wheel.
AB  - An alphabet soup of organizations and initiatives across the world are concerned
      with identifying, collecting and evaluating disease-causing human gene variants
      and using them to diagnose and treat rare diseases. Despite increasing
      standardization of nomenclature and technology, our efforts still need
      coordination to produce a pipeline leading from discovery to delivery.

PMID- 22366855
TI  - Emerging therapies for obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a prevalent disorder often associated with
      daytime sleepiness, cognitive dysfunction, and adverse cardiovascular
      consequences. Available therapies are limited by either lack of long-term
      adherence or low response rates. Two emerging therapies hold promise in providing
      alternatives to patients with OSA. The first stems from the importance of the
      upper-airway dilator muscles in maintaining pharyngeal stability. Electrical
      stimulation of the genioglossus muscle improves both upper-airway diameter and
      ameliorates pharyngeal obstruction. The results of phase I and II clinical trials
      hold promise, but the reported improvements in the apnea-hypopnea index vary
      between subjects and concerns about long-term safety await long-term studies. The
      second technology relies on creating an increased expiratory nasal resistance via
      a bidirectional valve designed to be worn just inside the nostrils. Initial
      findings of clinical trials suggest reduction in severity of sleep apnea and
      subjective daytime sleepiness. Considerable heterogeneity in response to the
      nasal device was noted despite the high adherence rates. It remains unclear which
      patients will likely benefit a priori from these devices.

PMID- 22366857
TI  - From HLA association to function.
AB  - A new study refines the association signals for rheumatoid arthritis
      susceptibility in the major histocompatibility complex (MHC) region to five amino
      acid positions encoded in three HLA genes, all within peptide-binding grooves. By
      adapting statistical methods from genome-wide association studies (GWAS) and
      using imputation from a large reference panel, they demonstrate the potential for
      this approach to identify functional variants in associated regions.

PMID- 22366858
TI  - Self-fertilization sweeps up variation in the worm genome.
AB  - A new study reports a comprehensive survey of genetic diversity in natural
      populations of the nematode Caenorhabditis elegans. Their analyses suggest that
      recent chromosome-scale selective sweeps have reduced C. elegans genetic
      diversity worldwide and strongly structured genetic variation across its genome.

PMID- 22366859
TI  - Connecting complex disorders through biology.
AB  - Mutations in CTC1, which encodes a key telomere component, have been identified
      as the cause of Coats plus syndrome. This discovery provides an important
      pathophysiological link between Coats plus and the clinically related telomere
      disorders dyskeratosis congenita, Revesz syndrome and Hoyeraal-Hreidarsson
      syndrome.

PMID- 22366865
TI  - Anti-inflammatory and neuroprotective effects of triptolide on traumatic brain
      injury in rats.
AB  - Traumatic brain injury (TBI) is characterized by neuroinflammation, brain edema,
      and cerebral damage leading to impairment of neurobehavioral function. Triptolide
      (PG-490), a diterpenoid component from Tripterygium wilfordii Hook F., has anti
      inflammatory properties. Whether triptolide has neuroprotective functions when
      treating TBI is unclear. To investigate this possibility, Sprague-Dawley rats
      were treated with triptolide immediately after TBI had been induced by a
      controlled cortical impact procedure or after a sham procedure. TBI produced
      neuroinflammation when measured on day 1 after TBI, induced cerebral damage when
      measured on day 1 and day 3, and impaired neurobehavioral functioning over a 28
      day observation period. Triptolide suppressed TBI-induced increases in contusion
      volume, cell apoptosis, edema and the levels of various pro-inflammatory
      mediators in the brain. Thriptolide reversed the TBI-induced decrease in brain
      levels of anti-inflammatory cytokine interleukin-10. Importantly, triptolide
      improved neurobehavioral outcomes regarding motor, sensory, reflex and balance
      function. We conclude that triptolide confers neuroprotection against TBI, at
      least in part, via its anti-inflammatory activity.

PMID- 22366866
TI  - Metabolic and heart rate responses to hypoxia in early chicken embryos in the
      transition from diffusive to convective gas transport.
AB  - Measurements of normoxic, hypoxic (15% or 10% O2) and post-hypoxic oxygen
      consumption (VO2) were conducted in chicken embryos every other day between
      embryonic day 3 (E3) and day 19 (E19), out of a total embryogenic period of 20.5
      days. The results indicated that, irrespective of age, hypoxia lowered VO2
      throughout embryogenesis without any contraction of an O2 debt. Hypoxic
      hypometabolism was more prominent at E3 than at E5, probably because of the
      differences in O2 sensitivity during the developmental transition from O2
      diffusion to O2 convection forms of gas transport. Further measurements at these
      two ages with either progressively increasing hypoxia or a sudden drop to 8% O2
      indicated that, at E5, the less pronounced hypometabolism was accompanied by a
      greater drop in heart rate (HR) than at E3. It was postulated that a functional
      causative link existed between these two phenomena, the decrease in whole-embryo
      [Formula: see text] favouring O2 availability to the heart. Indeed, when O2
      demands were decreased by cold exposure, the hypoxic effects on HR became similar
      between E3 and E5. We conclude that hypometabolism with no major reliance on
      anaerobic sources is the common response to hypoxia throughout embryogenesis. In
      the earliest phases of embryogenesis, when diffusion is the primary form of gas
      transport and despite the absence of neural regulation, the possibility of using
      some of the O2 saved in favour of the heart adds further value to hypometabolism
      as a survival strategy against hypoxia.

PMID- 22366867
TI  - Functional markers in wheat: current status and future prospects.
AB  - Functional markers (FM) are developed from sequence polymorphisms present in
      allelic variants of a functional gene at a locus. FMs accurately discriminate
      alleles of a targeted gene, and are ideal molecular markers for marker-assisted
      selection in wheat breeding. In this paper, we summarize FMs developed and used
      in common wheat. To date, more than 30 wheat loci associated with processing
      quality, agronomic traits, and disease resistance, have been cloned, and 97 FMs
      were developed to identify 93 alleles based on the sequences of those genes. A
      general approach is described for isolation of wheat genes and development of FMs
      based on in silico cloning and comparative genomics. The divergence of DNA
      sequences of different alleles that affect gene function is summarized. In
      addition, 14 molecular markers specific for alien genes introduced from common
      wheat relatives were also described. This paper provides updated information on
      all FMs and gene-specific STS markers developed so far in wheat and should
      facilitate their application in wheat breeding programs.

PMID- 22366868
TI  - Improvement of replication fidelity by certain mesalazine derivatives.
AB  - Epidemiological evidence on the chemopreventive activity of mesalazine against
      colitis-associated cancer has accumulated in recent years. Together with the
      variety of mesalazine molecular antitumor effects this has prompted the
      development of novel mesalazine derivatives. The objective of this study was to
      test five novel derivatives (compounds 2-14, 2-17, 2-28, 2-34L, 2-39) for their
      effect on cell proliferation, their capability to scavenge superoxide anions, to
      induce a cell cycle arrest and to improve replication fidelity in cultured
      colorectal cells. Compound 2-14 was identified as the strongest inhibitor of cell
      proliferation and functioned as a potent superoxide scavenger, as did 2-17 and 2
      34L. 2-14 induced a G2/M-arrest in HCT116 and a G0/G1-arrest in HT29 cells. 2-17
      caused a G0/G1-arrest and 2-34L a G2/M-arrest in HT29 cells. 2-17 and 2-34L
      reduced mutation rates at a (CA)13 repeat in a dose-dependent fashion. These data
      suggest that certain mesalazine derivatives share important antitumor effects.
      From this experimental profile compounds 2-17 and 2-34L both improve replication
      fidelity, which is biologically relevant not only for colitis-associated cancer
      but also potentially for individuals with hereditary non-polyposis colorectal
      cancer.

PMID- 22366869
TI  - Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis
      and improvement in gastrointestinal dysfunction: a pilot study.
AB  - OBJECTIVE: Clinical data demonstrating efficacy for nutraceutical compounds
      marketed for the symptom relief of osteoarthritis (OA) have been largely
      contentious. Furthermore, no association has been linked between clinical trial
      inconsistencies and gastrointestinal (GI) dysfunction. The aim of this study was
      to primarily investigate the efficacy of a high-dose New Zealand green-lipped
      mussel (GLM) extract in patients diagnosed with OA of the knee and concurrently
      assess GLM impact on GI function. METHODS: An open label, single group allocation
      study was conducted, that administered 3,000 mg/day of GLM extract over 8 weeks
      to 21 subjects diagnosed with knee OA. Outcome measures were scored using the
      WOMAC, the Lequesne algofunctional index, and the Gastrointestinal Symptom Rating
      Scale (GSRS) tools. An intention-to-treat analysis was employed and subject data
      collected at T0, T4 and T8 weeks. RESULTS: Paired t tests showed significant
      improvement for the Lequesne, WOMAC (p < 0.001) and GSRS (p = 0.005) scores. A
      repeated measures ANOVA analysis showed significant improvement in scores for the
      Lequesne (F = 20.317, p < 0.001), WOMAC (F = 28.383, p < 0.001) and the GSRS (F =
      9.221, p = 0.002). CONCLUSION: Green-lipped mussel significantly improved knee
      joint pain, stiffness and mobility. We report for the first time that the
      administration of GLM extract also significantly improved GI symptoms by 49% in
      OA patients. Given that GI dysfunction is linked to analgesic medication use, we
      further conclude that the therapeutic efficacy of the GLM extract used was
      possibly correlated to its effects on GI function by improving GSRS scores from
      baseline. Results from this trial highlight the requisite for further clinical
      investigations of gastrointestinal tract function in OA patients.

PMID- 22366870
TI  - Bonobos apparently search for a lost member injured by a snare.
AB  - This is the first report to demonstrate that a large mixed-sex party of bonobos
      travelled a long distance to return to the location of a snare apparently to
      search for a member that had been caught in it. An adult male was caught in a
      metallic snare in a swamp forest at Wamba, Luo Scientific Reserve, Democratic
      Republic of the Congo. After he escaped from the snare by breaking a sapling to
      which the snare was attached, other members of his party assisted him by
      unfastening the snare from lianas in which it was caught and licked his wound and
      tried to remove the snare from his fingers. In the late afternoon, they left him
      in the place where he was stuck in the liana and travelled to the dry forest
      where they usually spend the night. The next morning, they travelled back 1.8 km
      to revisit the location of the injured male. When they confirmed that he was no
      longer there, they returned to the dry forest to forage. This was unlike the
      usual ranging patterns of the party, suggesting that the bonobos travelled with
      the specific intention of searching for this injured individual who had been left
      behind. The incident described in this report likely occurred because bonobos
      usually range in a large mixed-sex party and try to maintain group cohesion as
      much as possible.

PMID- 22366871
TI  - Nanostructured Bi(2-x)Cu(x)S3 bulk materials with enhanced thermoelectric
      performance.
AB  - Nanostructured Bi(2-x)Cu(x)S(3) (x = 0, 0.002, 0.005, 0.007, 0.01, 0.03)
      thermoelectric polycrystals were fabricated by combining mechanical alloying (MA)
      and spark plasma sintering (SPS) methods. The effect of Cu content on the
      microstructure and thermoelectric property of Bi(2-x)Cu(x)S(3) bulk samples was
      investigated. It was found that the subtle tailoring of Cu content could reduce
      both the electrical resistivity and the thermal conductivity at the same time,
      and consequently enhancing the thermoelectric property. A low electrical
      resistivity of 1.34 * 10(-4)Omega m(-1) and a low thermal conductivity of 0.52 W
      m(-1) K(-1) were obtained for the Bi(1.995)Cu(0.005)S(3) sample at 573 K. The low
      thermal conductivity is supposed to be due to the nanoscopic Cu-rich regions
      embedded in the host matrix. A peak ZT value of 0.34 at 573 K was achieved for
      the Bi(1.995)Cu(0.005)S(3) composition, which is the highest value in the
      Bi(2)S(3) system reported so far.

PMID- 22366872
TI  - High intensity training induces alteration of the ubiquitin-proteasome system
      gene expression profile and structural changes in the ovaries.
AB  - The female reproductive system is highly sensitive to physiological stress.
      However, the mechanism(s) involved in dysfunction of the ovaries induced by high
      intensity exercise training remain unknown. In the present study, we established
      a rat model of high intensity exercise training, and investigated the
      morphological and functional changes in ovaries. Furthermore, we profiled the
      differential gene expression in the ovaries between high intensity exercise
      training rats and control rats by restriction fragment differential display PCR.
      Differentially expressed genes were validated by real-time PCR. The results
      showed that the weight and microstructure of the ovaries were significantly
      altered in the exercise training group rats. In addition, the levels of
      estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone
      were significantly decreased in the exercise training group rats compared with
      the control group rats. Immunohistochemistry revealed weak expression of
      estradiol, estrogen receptor and progesterone receptor in ovarian tissues from
      the high intensity exercise training group compared with the control group.
      Furthermore, the gene expression profiles of the exercise training and control
      group rats were analyzed, and differentially expressed genes, such as those
      involved in the ubiquitin-proteasome system, were identified. Our results
      indicate that high intensity exercise training can suppress the cellular function
      of the ovary glands. The mechanism may involve a series of alterations in the
      expression of genes particularly associated with the ubiquitin-proteasome system.

PMID- 22366873
TI  - Effects of a novel hydrogel on equine bone healing: a pilot study.
AB  - OBJECTIVE: To examine the efficacy and biocompatibility of a thiolated gelatin
      thiolated carboxymethyl hyaluronan (CMHA-SGX) sponge as an osteoconductive device
      in an equine second and fourth metacarpal bone defect model. METHODS: Seven
      millimetre segmental ostectomies were created bilaterally in the second and
      fourth metacarpal bones of four horses. The left and right metacarpal defects
      were randomly assigned to (1) be filled with a CMHA-SGX sponge (treated) or (2)
      were left unfilled (control). The duration of the study was nine weeks. Bone
      healing was evaluated using serial radiology, as well as histologically and
      histomorphometrically. Data were analyzed using an analysis of variance (ANOVA).
      The level of significance was p<0.05. RESULTS: Serial radiographic evaluation
      revealed improved healing in the treated compared to the control defects at weeks
      eight and nine (p = 0.02). This finding was not corroborated histologically.
      Histomorphometry did not reveal any significant differences in healing between
      experimental groups. The CMHA-SGX sponge did not inhibit bone formation, induce
      local inflammation or lead to surgical site infection. CLINICAL SIGNIFICANCE:
      While further optimization to improve osteoconductive properties should be
      considered, the CMHA-SGX sponge appears to be a biocompatible orthopaedic implant
      and its use as a carrier for osteogenic proteins warrants further investigation.

PMID- 22366875
TI  - Pseudohyperkalaemia associated with leukaemic cell lysis during pneumatic tube
      transport of blood samples.
AB  - BACKGROUND: Pseudohyperkalaemia is relatively uncommon in children, but needs to
      be considered in cases where extreme hyperkalaemia is associated with normal
      renal function. CASE: A previously well 12 year-old boy presented with new onset
      T cell acute lymphoblastic leukaemia associated with a high peripheral blood
      white cell count. Plasma biochemistry tests on a blood sample sent to the
      laboratory using a pneumatic tube system showed a high plasma potassium level of
      16.6 mmol/l, with otherwise normal electrolytes and renal function. A 12-lead
      electrocardiogram was normal, with no changes suggestive of hyperkalaemia.
      Pseudohyperkalaemia was suspected, and further samples transported to the
      laboratory by foot showed normal plasma potassium levels. It was subsequently
      demonstrated that the pseudohyperkalemia was due to the lysis of leukaemic white
      cells during the transport of blood samples from the ward to the laboratory
      within the pneumatic tube system. CONCLUSIONS: Paediatricians caring for children
      with haematological malignancies need to be aware of this cause of
      pseudohyperkalaemia so that unnecessary treatment, including the commencement of
      acute dialysis, is avoided. We recommend that blood samples collected from
      children with high white cell count malignancies are transported to the
      laboratory by foot rather than in pneumatic tube systems.

PMID- 22366874
TI  - Chronic kidney disease associated with perinatal HIV infection in children and
      adolescents.
AB  - BACKGROUND: This study describes the incidence, clinical and demographic
      characteristics, and spectrum of chronic kidney disease (CKD) in youths with
      perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and
      December 2006 of subjects with renal disease followed in the Pediatric AIDS
      Clinical Trials Group 219/219C multicenter study examining the long-term
      consequences of perinatal HIV infection. Diagnosis confirmation was made
      utilizing a questionnaire mailed to research sites. Participants with CKD of
      other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD
      and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using
      established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102
      participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases
      of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease
      (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2).
      Incidence rates for CKD associated with HIV in pre-highly active antiretroviral
      therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43,
      2.84, and 2.79 events per 1,000 person years respectively. In multivariate
      analysis, black race and viral load >=100,000 copies/mL (rate ratios 3.28 and
      5.05, p <= 0.02) were associated with CKD. CONCLUSIONS: A variety of immune
      complex-mediated glomerulonephritides and HIVAN occurs in this population. Black
      race and uncontrolled viral replication are risk factors for CKD associated with
      HIV.

PMID- 22366876
TI  - Native nephrectomy prior to pediatric kidney transplantation: biological and
      clinical aspects.
AB  - BACKGROUND: Pre-transplant nephrectomy is performed to reduce risks to graft and
      recipient. The aims of this study were to evaluate (1) indications, surgical
      approach, and morbidity of native nephrectomy and (2) the effects of kidney
      removal on clinical and biological parameters. METHODS: This study was designed
      as a single-center retrospective cohort study in which 49 consecutive patients
      with uni- or bilateral native nephrectomies were identified from a total of 126
      consecutive graft recipients in our pediatric kidney transplantation database
      between 1992 and 2011. Demographic, clinical, and laboratory details were
      extracted from charts and electronic records, including operation reports and pre
      and post-operative clinic notes. RESULTS: Of the 49 nephrectomized patients, 47%
      had anomalies of the kidneys and urinary tract, 22% had cystinosis, 12% had focal
      segmental glomerulosclerosis, and 6% had congenital nephrotic syndrome.
      Nephrectomy decisions were based on clinical judgment, taking physiological and
      psychosocial aspects into consideration. Nephrectomy was performed in patients
      with polyuria (>2.5 ml/kg/h) and/or large proteinuria (>40 mg/m(2)/h), recurrent
      urinary tract infection or (rarely) hypertension. Urine output decreased from
      (median) 3.79 to 2.32 ml/kg/h (-34%), and proteinuria from 157 to 100 mg/m(2)/h (
      40%) after unilateral nephrectomy (p=0.005). After bilateral nephrectomy, serum
      albumin, protein and fibrinogen concentrations normalized in 93, 73, and 55% of
      nephrectomized patients, respectively. Clinically relevant procedure-related
      complications (peritoneal laceration, hematoma) occurred in five patients.
      CONCLUSION: In summary, we demonstrate quantitatively that native nephrectomy
      prior to transplantation improved serum protein levels and anticipated post
      transplant fluid intake needs in select children, reducing the risk of graft
      hypoperfusion and its postulated consequences for graft outcome.

PMID- 22366877
TI  - Hyponatremic hypertensive syndrome in pediatric patients: is it really so rare?
AB  - BACKGROUND: Hyponatremic hypertensive syndrome (HHS) is characterized by
      unilateral renal artery stenosis with secondary hypertension and glomerular and
      tubular dysfunction due to hyperfiltration and activation of the renin
      angiotensin system (RAS). CASE-DIAGNOSIS/TREATMENT: We describe four children
      with HHS. All presented with polyuria and polydipsia, electrolyte disturbances,
      metabolic alkalosis, variable tubular dysfunction, and nephrotic range
      proteinuria along with hypertension. Interestingly, in one patient, glomerular
      and tubular abnormalities preceded the development of hypertension. All symptoms
      resolved after the underlying renal ischemia was corrected by percutaneous
      angioplasty. CONCLUSION: Hyponatremic hypertensive syndrome may be more common in
      children than previously thought. Clinicians should be alert of the signs and
      symptoms because cure is possible with timely diagnosis and treatment.

PMID- 22366878
TI  - Long-term benefits of progressive resistance training in chronic stroke: a 4-year
      follow-up.
AB  - OBJECTIVES: To evaluate the long-term benefits of progressive resistance training
      in chronic stroke. DESIGN: A 4-year follow-up of a randomized controlled trial of
      progressive resistance training. SUBJECTS: Eighteen women and men (mean age 66
      (standard deviation 4) from the original group of 24 post-stroke participants.
      METHODS: The training group (n = 11) had participated in supervised progressive
      resistance training of the knee extensors and flexors (80% of maximum) twice
      weekly for 10 weeks, whereas the control group (n = 7) had continued their usual
      daily activities. Muscle strength was evaluated isotonically and isokinetically
      (60o/s; Biodex), muscle tone with the Modified Ashworth Scale, gait performance
      by the Timed Up and Go test, the Fast Gait Speed test and 6-Minute Walk test, and
      perceived participation with the Stroke Impact Scale (Participation domain).
      RESULTS: Four years after the intervention, the improvements in muscle strength
      in the training group were maintained, and there was no reduction in strength in
      the control group. Compared with baseline there were still significant between
      group differences for both isotonic and isokinetic strength. No significant
      between-group differences were found in muscle tone, gait performance or
      perceived participation. CONCLUSION: The results indicate that there is a long
      term benefit of progressive resistance training in chronic stroke. This implies
      that progressive resistance training could be an effective training method to
      improve and maintain muscle strength in a long-term perspective.

PMID- 22366879
TI  - Association study between glucocorticoid receptor gene polymorphisms and
      personality traits in healthy Japanese individuals.

PMID- 22366880
TI  - Tuning the band gaps and work functions via topology and carbon concentration: a
      first-principles investigation of C(x)(BN)(y) compounds.
AB  - The electronic properties, stabilities, and work functions of C(x)(BN)(y)
      monolayers were systematically investigated by first-principle techniques. The
      results indicated that the band gaps of the systems are rather sensitive to the
      topology and symmetry. However, the formation energies clearly suggested that the
      BN dimers tend to be grouped to one side and the carbon atoms are grouped to the
      other side. Such an atomic arrangement has the lowest formation energy and is
      thermodynamically highly stable, and furthermore their band gaps decrease
      gradually with an increasing of carbon content. Further analysis revealed that
      the band gap narrowing of G(I) structures depends on the nature of the C-2p(z)
      and N-2p(z) states. In contrast to the electronic properties, the variation of
      work functions as functions of carbon content exhibits an opposite trend. The
      strong correlation between the positive charge (Q(pos.)(tot.)) :work function
      (W(C(x)(BN)(y))) ratio and carbon content indicated that the ionicity of
      C(x)(BN)(y) compounds can be controlled by the carbon content and therefore
      determine the work functions of the systems.

PMID- 22366881
TI  - Microvascular autoregulation in children and adolescents with type 1 diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: Deterioration of microvascular function may have an early onset
      in individuals with type 1 diabetes mellitus. We hypothesised that microvascular
      autoregulation is impaired in children with type 1 diabetes and can be detected
      non-invasively by postocclusive reactive hyperaemia (PORH). METHODS:
      Microvascular autoregulation was assessed in 58 children with type 1 diabetes and
      58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry.
      Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal
      during suprasystolic occlusion), peak perfusion following occlusion, time to peak
      and recovery time (time until baseline perfusion is resumed) were recorded and
      compared between the groups. RESULTS: Peak perfusion was higher in children with
      type 1 diabetes than in healthy controls (1.7 +/- 0.93 AU [arbitrary units] vs
      1.29 +/- 0.46 AU; p = 0.004), and biological zero was lower in children with type
      1 diabetes vs controls (0.14 +/- 0.04 AU vs 0.19 +/- 0.04 AU; p < 0.0001). No
      differences were seen between the groups in baseline perfusion, time to peak
      during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION: PORH
      reveals impaired microvascular autoregulation in children with type 1 diabetes.
      The higher peak perfusion might reflect a decline in the vasoconstrictive ability
      of arteriolar smooth muscle cells upstream of capillary beds in children with
      type 1 diabetes.

PMID- 22366882
TI  - Differential susceptibility effects: the interaction of negative emotionality and
      sibling relationship quality on childhood internalizing problems and social
      skills.
AB  - Whereas socialization influences in early childhood have been linked to
      children's emerging internalizing problems and prosocial behavior, relatively few
      studies have examined how NE might moderate such associations in both
      advantageous and maladaptive ways. Furthermore, more research is needed to
      evaluate the impact of sibling relationships as an influential socialization
      influence on these child outcomes. In the current study we examined how NE might
      differentially moderate the associations between quality of relationships with
      siblings and both internalizing problems and social skills at school entry. NE
      moderated the effects of positive and destructive sibling relationship quality on
      child internalizing problems. Specifically, for boys high on NE, more positive
      sibling relationship quality predicted fewer internalizing problems, but more
      destructive sibling conflict predicted more internalizing problems. NE also
      moderated the effects of destructive sibling conflict on child social skills. For
      boys high on NE, destructive sibling conflict predicted fewer social skills. Boys
      high on NE appear to show greater susceptibility to the effects of sibling
      socialization on child outcomes, relative to boys low on NE. The implications of
      these interactions are discussed with respect to differential susceptibility
      theory.

PMID- 22366884
TI  - Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+ channel
      activity by the phosphorylation of alpha1c proteins.
AB  - Dendroaspis natriuretic peptide (DNP), a new member of the natriuretic peptide
      family, is structurally similar to atrial, brain, and C-type natriuretic
      peptides. However, the effects of DNP on the cardiac function are poorly defined.
      In the present study, we examined the effect of DNP on the cardiac L-type Ca(2+)
      channels in rabbit ventricular myocytes. DNP inhibited the L-type Ca(2+) current
      (I(Ca,L)) in a concentration dependent manner with a IC(50) of 25.5 nM, which was
      blocked by an inhibitor of protein kinase G (PKG), KT5823 (1 MUM). DNP did not
      affect the voltage dependence of activation and inactivation of I(Ca,L). The
      alpha(1c) subunit of cardiac L-type Ca(2+) channel proteins was phosphorylated by
      the treatment of DNP (1 MUM), which was completely blocked by KT5823 (1 MUM).
      Finally, DNP also caused the shortening of action potential duration in rabbit
      ventricular tissue by 22.3 +/- 4.2% of the control (n = 6), which was completely
      blocked by KT5823 (1 MUM). These results clearly indicate that DNP inhibits the L
      type Ca(2+) channel activity by phosphorylating the Ca(2+) channel protein via
      PKG activation.

PMID- 22366883
TI  - Inactivation or non-reactivation: what accounts better for the silence of sex
      chromosomes during mammalian male meiosis?
AB  - During the first meiotic prophase in male mammals, sex chromosomes undergo a
      program of transcriptional silencing called meiotic sex chromosome inactivation
      (MSCI). MSCI is triggered by accumulation of proteins like BRCA1, ATR, and
      gammaH2AX on unsynapsed chromosomes, followed by local changes on the sex
      chromatin, including histone modifications, incorporation of specific histone
      variants, non-histone proteins, and RNAs. It is generally thought that MSCI
      represents the transition of unsynapsed chromatin from a transcriptionally active
      state to a repressed state. However, transcription is generally low in the whole
      nucleus during the early stages of the first meiotic prophase, when markers of
      MSCI first appear, and is then reactivated globally during pachytene. Thus, an
      alternative possibility is that MSCI represents the targeted maintenance and/or
      reinforcement of a prior repressed state, i.e., a failure to reactivate. Here, we
      present an analysis of the temporal and spatial appearance of transcriptional and
      MSCI markers, as well as chromatin modifications related to transcriptional
      regulation. We show that levels of RNA pol II and histone H3 acetylated at lysine
      9 (H3K9ac) are low during leptotene, zygotene, and early pachytene, but increase
      strongly in mid-pachytene, indicating that reactivation occurs with some delay
      after synapsis. However, while transcription markers appear abundantly on the
      autosomes at mid-pachytene, they are not directed to the sex chromosomes.
      Interestingly, we found that chromatin modifications related to transcriptional
      silencing and/or MSCI, namely, histone H3 trimethylated at lysine 9 (H3K9me3),
      histone H3 monomethylated at lysine 4 (H3K4me1), gammaH2AX, SUMO1, and XMR,
      appear on the sex chromosomes before autosomes become reactivated. These results
      suggest that the onset of MSCI during late zygotene and early pachytene may
      prevent sex chromosome reactivation during mid-pachytene instead of promoting
      inactivation de novo. Additionally, we found temporal differences between the X
      and Y chromosomes in the recruitment of DNA repair and MSCI markers, indicating a
      differential regulation of these processes. We propose that many of the meiotic
      defects attributed to failure to silence sex chromosomes could be interpreted as
      a more general process of transcriptional misregulation that occurs under certain
      pathological circumstances in zygotene and early pachytene.

PMID- 22366885
TI  - Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells.
AB  - The antitumor effects of ginsenoside Rg3 have been reported in several kinds of
      human malignant tumors. The purpose of this study was to investigate whether
      ginsenoside Rg3 can inhibit the growth of human hepatocellular carcinoma cell
      lines and to discuss the possible molecular mechanism(s). We cultured the human
      hepatocellular carcinoma cell lines, SMMC-7721 and HepG2. The cells were treated
      with different concentrations of ginsenoside Rg3 (0, 25, 50, 75 and 100 ug/ml),
      and the cell proliferation was detected by MTT assay at the 12, 24, 36 and 48 h
      time-points. Flow cytometry experiments were carried out to investigate the
      effect of Rg3 on cell apoptosis after the cells had been treated with Rg3 (50 and
      100 ug/ml) for 24 and 48 h. The expression levels of caspase-3, bax and bcl-2 in
      Rg3-treated cells (100 ug/ml, 48 h), as well as normal cells were detected
      through real-time PCR experiments. MTT assay showed that the inhibition rate of
      cell proliferation in the Rg3 groups was significantly higher compared to the
      control groups in both the SMMC-7721 and HepG2 cell lines, and the inhibition
      rate increased with increasing Rg3 concentrations and duration of treatment. Flow
      cytometry analysis demonstrated that the Rg3 groups had a significantly higher
      cell apoptotic rate compared to the control groups in both the SMMC-7721 and
      HepG2 cell lines, and that the effect of Rg3 on cell apoptosis occurred in a
      concentration- and time-dependent manner, as was also shown by the MTT assay.
      Real-time PCR analysis showed that the gene expression levels of caspase-3 and
      bax were significantly enhanced in the Rg3 groups compared to the control groups
      in both the SMMC-7721 and HepG2 cell lines, but the gene expression level of bcl
      2 was significantly inhibited. These results indicate that ginsenoside Rg3 can
      effectively inhibit the growth of human hepatocellular carcinoma cell lines by
      inhibiting cancer cell proliferation and promoting cancer cell apoptosis, and it
      may promote cancer cell apoptosis via the endogenous mitochondrial-mediated
      caspase-dependent apoptotic pathway.

PMID- 22366886
TI  - Enhanced activation of human dendritic cells by silencing SOCS1 and activating
      TLRs simultaneously.
AB  - There was established evidence that silencing the attenuator and activating the
      TLRs could activate the dendritic cells in synergic effects. In this study, we
      constructed a plasmid, namely pshS1NH, which encodes SOCS1-shRNA, NY-ESO-1-MAGE3
      (HLA-A2*0201) fusion antigen and secretory HMGB1, an agent used to modify
      dendritic cells (DCs), aiming to generate potent DC vaccine against tumors. The
      SOCS1-shRNA could efficiently downregulate the expression of SOCS1, as indicated
      by real-time RT-PCR and Western blot. The fusion antigen was detected in the
      pshS1NH-DCs by PCR and Western blot. Simultaneously, HMGB1 level in the pshS1NH
      DCs culture media was significantly higher than that in the control DCs culture
      media. Levels of Th1 cytokines in pshS1NH-DCs culture media, such as IL-1beta, IL
      6, TNF-alpha and IL-12p70, were dramatically higher than those in control DCs
      culture media. In addition, lymphocytes co-cultured with pshS1NH-DCs secreted
      dramatically higher level of IFN-gamma, whereas no difference was detected in IL
      4 levels. Taken together, these data suggest that pshS1NH-DCs may be a potential
      adjuvant immunotherapy for cancers in clinical applications.

PMID- 22366887
TI  - Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer
      diagnosis and therapy.
AB  - The thymus is a central lymphoid organ with crucial role in generating T cells
      and maintaining homeostasis of the immune system. More than 30 peptides,
      initially referred to as "thymic hormones," are produced by this gland. Although
      the majority of them have not been proven to be thymus-specific, thymic peptides
      comprise an effective group of regulators, mediating important immune functions.
      Thymosin fraction five (TFV) was the first thymic extract shown to stimulate
      lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led
      to the isolation and characterization of a series of immunoactive
      peptides/polypeptides, members of the thymosin family. Extensive research on
      prothymosin alpha (proTalpha) and thymosin alpha1 (Talpha1) showed that they are
      of clinical significance and potential medical use. They may serve as molecular
      markers for cancer prognosis and/or as therapeutic agents for treating
      immunodeficiencies, autoimmune diseases and malignancies. Although the molecular
      mechanisms underlying their effect are yet not fully elucidated, proTalpha and
      Talpha1 could be considered as candidates for cancer immunotherapy. In this
      review, we will focus in principle on the eventual clinical utility of proTalpha,
      both as a tumor biomarker and in triggering anticancer immune responses.
      Considering the experience acquired via the use of Talpha1 to treat cancer
      patients, we will also discuss potential approaches for the future introduction
      of proTalpha into the clinical setting.

PMID- 22366888
TI  - Bilateral angular carpal deformity in a dog with craniomandibular osteopathy.
AB  - A four-month-old West Highland White Terrier was presented to the Small Animal
      Teaching Hospital at the University of Liverpool with the complaint of a
      bilateral angular carpal deformity. A 20 degrees  valgus deformity was present in
      both thoracic limbs, centred on the distal radial physes. Both distal ulnas were
      grossly thickened and there was concomitant thickening of the rostral mandible
      and calvarium. The dog exhibited signs of resentment on palpation of the mandible
      and signs of pain were elicited on flexion and extension of both elbow joints. No
      signs of pain were evident on palpation of the ulnas or calvarium. Radiographic
      images of both ulnas showed marked amorphous periosteal new bone formation. The
      distal ulnar physes were closed centrally and both elbow joints had humeroulnar
      subluxation. Radiographic changes to the calvarium and mandibular rami were
      consistent with a diagnosis of craniomandibular osteopathy. A bilateral ulna
      ostectomy was performed to correct the angular limb deformity and elbow
      subluxations. Histology of the ostectomised pieces showed changes consistent with
      craniomandibular osteopathy.

PMID- 22366889
TI  - Absolute quantitation of brain metabolites with respect to heterogeneous tissue
      compositions in (1)H-MR spectroscopic volumes.
AB  - OBJECT: Referencing metabolite intensities to the tissue water intensity is
      commonly applied to determine metabolite concentrations from in vivo (1)H-MRS
      brain data. However, since the water concentration and relaxation properties
      differ between grey matter, white matter and cerebrospinal fluid (CSF), the
      volume fractions of these compartments have to be considered in MRS voxels.
      MATERIALS AND METHODS: The impact of partial volume correction was validated by
      phantom measurements in voxels containing mixtures of solutions with different
      NAA and water concentrations as well as by analyzing in vivo (1)H-MRS brain data
      acquired with various voxel compositions. RESULTS: Phantom measurements indicated
      substantial underestimation of NAA concentrations when assuming homogeneously
      composed voxels, especially for voxels containing solution, which simulated CSF
      (error: <= 92%). This bias was substantially reduced by taking into account voxel
      composition (error: <= 10%). In the in vivo study, tissue correction reduced the
      overall variation of quantified metabolites by up to 35% and revealed the
      expected metabolic differences between various brain tissues. CONCLUSIONS: Tissue
      composition affects extraction of metabolite concentrations and may cause
      misinterpretations when comparing measurements performed with different voxel
      sizes. This variation can be reduced by considering the different tissue types by
      means of combined analysis of spectroscopic and imaging data.

PMID- 22366890
TI  - Differential expression profiles of sense and antisense transcripts between HCV
      associated hepatocellular carcinoma and corresponding non-cancerous liver tissue.
AB  - Recent studies have demonstrated that natural antisense transcripts, which are
      complementary sequences to messenger RNA, have important cellular functions such
      as the stabilization and silencing of mRNA. However, the possible contribution of
      antisense transcripts in hepatocellular carcinoma (HCC) development has not been
      described. Therefore, we simultaneously investigated the sense and antisense
      transcripts of HCC and non-cancerous tissues to explore the possible contribution
      of antisense transcripts to HCC progression. RNA was prepared from 15 HCV
      associated HCCs and from 6 corresponding non-cancerous tissues and was subjected
      to expression profile analysis of sense and antisense transcripts using a human
      custom microarray. Differential expression of 161 sense and 25 antisense
      transcripts was observed with more than 2-fold between HCC and non-cancerous
      tissue (p<0.001). The expression of the sense and antisense transcripts was used
      to cluster cancer and non-cancerous tissues, and the cancer and non-cancerous
      tissues were found to be clearly separated into different clusters. Additionally,
      the sense and antisense expression profiles were analyzed with regard to HCC
      differentiation (p<0.001), resulting in 71 sense and 43 antisense transcripts.
      These unique transcripts did not overlap with those found in the discrimination
      of HCC from non-cancerous tissues. When the HCC tissues were clustered by
      transcript expression, the antisense transcripts resulted in clustering of HCC
      that was consistent with grouping based on histology. These findings strongly
      indicate that the antisense transcripts together with the sense transcripts are
      involved in liver tumorigenesis.

PMID- 22366891
TI  - The kinase Btk negatively regulates the production of reactive oxygen species and
      stimulation-induced apoptosis in human neutrophils.
AB  - The function of the kinase Btk in neutrophil activation is largely unexplored.
      Here we found that Btk-deficient neutrophils had more production of reactive
      oxygen species (ROS) after engagement of Toll-like receptors (TLRs) or receptors
      for tumor-necrosis factor (TNF), which was associated with more apoptosis and was
      reversed by transduction of recombinant Btk. Btk-deficient neutrophils in the
      resting state showed hyperphosphorylation and activation of phosphatidylinositol
      3-OH kinase (PI(3)K) and protein tyrosine kinases (PTKs) and were in a 'primed'
      state with plasma membrane-associated GTPase Rac2. In the absence of Btk, the
      adaptor Mal was associated with PI(3)K and PTKs at the plasma membrane, whereas
      in control resting neutrophils, Btk interacted with and confined Mal in the
      cytoplasm. Our data identify Btk as a critical gatekeeper of neutrophil
      responses.

PMID- 22366892
TI  - IgE+ memory B cells and plasma cells generated through a germinal-center pathway.
AB  - Immunoglobulin E (IgE) antibodies are pathogenic in asthma and allergic diseases,
      but the in vivo biology of IgE-producing (IgE(+)) cells is poorly understood. A
      model of the differentiation of IgE(+) B cells proposes that IgE(+) cells develop
      through a germinal-center IgG1(+) intermediate and that IgE memory resides in the
      compartment of IgG1(+) memory B cells. Here we have used a reporter mouse
      expressing green fluorescent protein associated with membrane IgE transcripts
      (IgE-GFP) to assess in vivo IgE responses. In contrast to the IgG1-centered model
      of IgE switching and memory, we found that IgE(+) cells developed through a
      germinal-center IgE(+) intermediate to form IgE(+) memory B cells and plasma
      cells. Our studies delineate a new model for the in vivo biology of IgE switching
      and memory.

PMID- 22366893
TI  - Early window of diabetes determinism in NOD mice, dependent on the complement
      receptor CRIg, identified by noninvasive imaging.
AB  - All juvenile mice of the nonobese diabetic (NOD) strain develop insulitis, but
      there is considerable variation in their progression to diabetes. Here we used a
      strategy based on magnetic resonance imaging (MRI) of magnetic nanoparticles to
      noninvasively visualize local effects of pancreatic-islet inflammation to predict
      the onset of diabetes in NOD mice. MRI signals acquired during a narrow early
      time window allowed us to sort mice into groups that would progress to clinical
      disease or not and to estimate the time to diabetes development. We exploited
      this approach to identify previously unknown molecular and cellular elements
      correlated with disease protection, including the complement receptor of the
      immunoglobulin superfamily (CRIg), which marked a subset of macrophages
      associated with diabetes resistance. Administration of a fusion of CRIg and the
      Fc portion of immunoglobulin resulted in lower MRI signals and diabetes
      incidence. In addition to identifying regulators of disease progression, we show
      here that diabetes is set at an early age in NOD mice.

PMID- 22366894
TI  - Managing spastic hypertonia in children with cerebral palsy via repetitive
      passive knee movements.
AB  - OBJECTIVE: Most children with cerebral palsy have increased muscle tension in the
      lower extremities, which inevitably leads to abnormal gait characteristics.
      Proper management of excessive muscle tension is therefore of great importance.
      The aim of this study was to explore the effects of continuous passive motion on
      children with cerebral palsy, regarding their lower extremity spastic hypertonia
      and ambulatory function. DESIGN: A repeated measures design. SUBJECTS: Sixteen
      children with cerebral palsy. METHODS: Intervention was applied to the subject's
      knees with a continuous passive motion device (at velocities of 15 and 0o/s) for
      20 min. Effects were evaluated via variables measuring range-of-motion, muscle
      tone, and ambulatory function before, immediately after, and 30 min after
      intervention. RESULTS: For the 15o/s intervention, significant differences were
      found in time, intervention, and interaction among variables, including active
      range-of-motion of the knee (increased), relaxation index (increased), Modified
      Ashworth Scale (decreased), Timed Up-and-Go (decreased), and 6-Minute Walk test
      (increased). No difference was found in passive range of motion measurements. For
      the 0o/s control condition, none of the dependent variables demonstrated
      statistically significant differences. CONCLUSION: Repetitive passive movement
      can reduce lower extremity spastic hypertonia in children with cerebral palsy,
      and improve ambulatory function in terms of walking speed.

PMID- 22366895
TI  - Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress
      in cerebellum of rats.
AB  - Methyl mercury (MeHg) is a ubiquitous environmental pollutant leading to
      neurological and developmental deficits in animals and human beings. Bacopa
      monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a
      traditional medicine system in India. The objective of the present study was to
      investigate whether Bacopa monniera extract (BME) could potentially inhibit MeHg
      induced toxicity in the cerebellum of rat brain. Male Wistar rats were
      administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental
      rats were given MeHg and also administered with BME (40 mg/kg, orally) for 21
      days. After the treatment period, we observed that MeHg exposure significantly
      inhibited the activities of superoxide dismutase, catalase, glutathione
      peroxidase, and increased the glutathione reductase activity in cerebellum. It
      was also found that the level of thiobarbituric acid-reactive substances was
      increased with the concomitant decrease in the glutathione level in MeHg-induced
      rats. These alterations were prevented by the administration of BME. Behavioral
      interference in the MeHg-exposed animals was evident through a marked deficit in
      the motor performance in the rotarod task, which was completely recovered to
      control the levels by BME administration. The total mercury content in the
      cerebellum of MeHg-induced rats was also increased which was measured by atomic
      absorption spectrometry. The levels of NO(2) (-) and NO(3) (-) in the serum were
      found to be significantly increased in the MeHg-induced rats, whereas treatment
      with BME significantly decreased their levels in serum to near normal when
      compared to MeHg-induced rats. These findings strongly implicate that BM has
      potential to protect brain from oxidative damage resulting from MeHg-induced
      neurotoxicity in rat.

PMID- 22366896
TI  - Continuous renal replacement therapy in children.
AB  - Over the past several decades, the epidemiology of acute kidney injury (AKI) in
      children has changed significantly. Pediatric patients with AKI frequently have
      co-morbid conditions, substantial fluid overload, and marked disease severity. At
      the same time, continuous renal replacement therapy (CRRT) has become the
      preferred modality for the management of these patients. This manuscript provides
      a state-of-the-art review of the technical aspects of pediatric CRRT and examines
      the most recent data regarding CRRT indications, timing of initiation, dosing,
      and outcomes in critically ill children.

PMID- 22366897
TI  - Migration background and patient satisfaction in a pediatric nephrology
      outpatient clinic.
AB  - BACKGROUND: We examined the association of a migration background and patient
      satisfaction in a pediatric nephrology outpatient clinic in Germany. METHODS:
      This was a cross-sectional study of 348 families presenting at the Pediatric
      Nephrology Outpatient Department of Charite University Children's Hospital in
      Berlin during 2008. Parents were asked to complete a questionnaire containing
      basic sociodemographic information, a subjective categorical rating of disease
      severity and communication with the medical team, and a validated patient
      satisfaction score (ZUF-8) derived from a customer satisfaction score used by
      industry and modified for healthcare providers. RESULTS: Of the 348 families
      included in the study, 131 patients (38 %) had a migration background (20
      different nationalities, 22 different native languages). Patient satisfaction
      (rated on a scale from 8 to 40) was significantly higher in families without
      (32.9  +/-  4.6) than in those with a migration background (30.8  +/-  4.7; p <
      0.0001). A multivariate linear regression analysis revealed that trust in
      doctors, friendliness of the doctor, severity of the child's disease, number of
      medications prescribed, and a migration background were significantly and
      independently correlated with patient satisfaction. CONCLUSIONS: Migrant families
      were less satisfied with the provision of the outpatient care provided by our
      department than non-migrants.

PMID- 22366899
TI  - Repeatability and reproducibility of retinal thickness measurements with spectral
      domain optical coherence tomography using different scan parameters.
AB  - PURPOSE: To evaluate repeatability (test-retest) and reproducibility of retinal
      thickness measurements using spectral-domain optical coherence tomography with
      different densities of A-scans per B-scan and different frames per B-scan for
      real-time averaging. METHODS: Twelve healthy subjects were analyzed by spectral
      domain optical coherence tomography. Raster lines analysis with 19 B-scans over
      the examined area centered on the macula was performed. Images were acquired both
      in standard-density (768 A-scans/B-scan) and high-density (1,536 A-scans/B-scan)
      modalities. Moreover, images were acquired using 2 and 20 frames/B-scan for real
      time averaging. Each analysis was repeated twice to test for repeatability.
      RESULTS: Intersession repeatability was good for all studied analysis protocols,
      with Lin concordance correlation coefficient values ranging between 0.88 and
      1.00. Reproducibility assessment showed consistent retinal thickness measurements
      using variable scan density, with Bland-Altman limits of agreement of -6 MUm to 6
      MUm in the central area. Reproducibility assessment showed consistent retinal
      thickness measurements using different number of frames used in the real-time
      averaging process, with Bland-Altman limits of agreement of -8 MUm to 4 MUm in
      the central area. CONCLUSION: Spectral-domain optical coherence tomography is a
      very reliable tool for central retinal thickness assessment. Changes in the
      number of A-scans/B-scan and in frames used for real-time averaging do not affect
      repeatability and reproducibility.

PMID- 22366898
TI  - Proteomics of mouse BRCA1-deficient mammary tumors identifies DNA repair proteins
      with potential diagnostic and prognostic value in human breast cancer.
AB  - Breast cancer 1, early onset (BRCA1) hereditary breast cancer, a type of cancer
      with defects in the homology-directed DNA repair pathway, would benefit from the
      identification of proteins for diagnosis, which might also be of potential use as
      screening, prognostic, or predictive markers. Sporadic breast cancers with
      defects in the BRCA1 pathway might also be diagnosed. We employed proteomics
      based on one-dimensional gel electrophoresis in combination with nano-LC-MS/MS
      and spectral counting to compare the protein profiles of mammary tumor tissues of
      genetic mouse models either deficient or proficient in BRCA1. We identified a
      total of 3,545 proteins, of which 801 were significantly differentially regulated
      between the BRCA1-deficient and -proficient breast tumors. Pathway and protein
      complex analysis identified DNA repair and related functions as the major
      processes associated with the up-regulated proteins in the BRCA1-deficient
      tumors. In addition, by selecting highly connected nodes, we identified a BRCA1
      deficiency signature of 45 proteins that enriches for homology-directed DNA
      repair deficiency in human gene expression breast cancer data sets. This
      signature also exhibits prognostic power across multiple data sets, with optimal
      performance in a data set enriched in tumors deficient in homology-directed DNA
      repair. In conclusion, by comparing mouse proteomes from BRCA1-proficient and 
      deficient mammary tumors, we were able to identify several markers associated
      with BRCA1 deficiency and a prognostic signature for human breast cancer
      deficient in homology-directed DNA repair.

PMID- 22366900
TI  - Combined high-dose sub-tenon triamcinolone, intravitreal bevacizumab, and laser
      photocoagulation for refractory diabetic macular edema: a pilot study.
AB  - PURPOSE: To study the efficacy and safety of triple therapy (sub-Tenon
      triamcinolone [~70 mg], intravitreal bevacizumab [1.25 mg], and focal/grid laser)
      for refractory diabetic macular edema. METHOD: Twenty-nine eyes of 29 patients
      who received triple therapy were monitored for central foveal thickness, best
      corrected visual acuity (BCVA), and side effects over a 1-year period. Their
      results were compared with a focal/grid laser historical control group of 18 eyes
      (18 patients). RESULTS: In the triple therapy group, mean central foveal
      thickness significantly reduced from baseline value of 441 MUm to 298 MUm at
      Month 12 (P < 0.001), but there was no significant change of BCVA. In the control
      group, there were no sustained significant changes of central foveal thickness or
      BCVA. A subgroup analysis of 7 eyes in the triple therapy group with baseline
      BCVA of <=20/100 showed significant BCVA improvements from 4 weeks to 9 months.
      The maximum improvement was achieved at 6 months, when the mean BCVA improved by
      9.5 Early Treatment Diabetic Retinopathy Study letters from baseline. Intraocular
      pressure rise (31.0%), partial ptosis (17.2%), and significant cataractogenesis
      (8.7%) were encountered in the triple therapy group but not in the control group.
      CONCLUSION: Sustained reduction of central foveal thickness was achieved with
      triple therapy over the 1-year study period. Significant visual improvement was
      seen only in patients with worse baseline BCVA, but not in the triple therapy
      group as a whole. Significant side effects of intraocular pressure rise, ptosis,
      and cataractogenesis were encountered in the triple therapy group.

PMID- 22366901
TI  - Sutureless 23-gauge versus 20-gauge vitrectomy with silicone oil injection in
      rhegmatogenous retinal detachment.
AB  - PURPOSE: To report the efficacy of 23-gauge (G) pars plana vitrectomy with
      silicone oil injection in rhegmatogenous retinal detachment. METHODS:
      Retrospective chart review of consecutive patients with retinal detachment who
      underwent pars plana vitrectomy by one of two surgeons using distinct and
      consistent methods. All patients undergoing 23-G pars plana vitrectomy did not
      have scleral buckling, whereas all patients undergoing surgery by 20-G pars plana
      vitrectomy had additional 240-band encircling scleral buckle. All patients
      received silicone oil tamponade. Patients with proliferative vitreoretinopathy
      Grade D, previous retinal detachment surgery, and penetrating eye injury were
      excluded. The main outcome measure was the final anatomical reattachment rate.
      The secondary outcome measures were the improvement in visual acuity and
      recurrence rate of retinal detachment after primary surgery. RESULTS: Eighteen
      patients in the 23-G group and 21 patients in the 20-G group were analyzed. The
      mean age of the patients was 48.05 +/- 10.37 years and 42.57 +/- 17.84 years in
      the 23-G and 20-G groups, respectively. The mean follow-up duration was 5.9
      months (range, 2-12 months) and 6.2 months (range, 4-9 months) in the 23-G and 20
      G groups, respectively. The primary reattachment rate was 83.3% (95% confidence
      interval, 66.11%-100%) in the 23-G group and 86.8% (95% confidence interval,
      67.81%-100%); P = 1.00) in 20-G group. The mean preoperative logarithm of the
      minimum angle of resolution visual acuity was 1.30 +/- 0.57 (Snellen equivalent
      20/400) in the 23-G group and 1.27 +/- 0.70 (Snellen equivalent 20/400) in the 20
      G group (P = 0.80). The mean logarithm of the minimum angle of resolution visual
      acuity at 1 month after the surgery was 0.66 +/- 0.25 (Snellen equivalent 20/100)
      in the 23-G group and 0.77 +/- 0.50 (Snellen equivalent 20/120; P = 0.46) in the
      20-G group. The visual acuity at the last visit was 0.80 +/- 0.52 (20/125) versus
      0.65 +/- 0.44 (20/100) in the 23-G and 20-G, respectively (P = 0.32). CONCLUSION:
      Silicone oil injection with 23-G system is possible and is associated with
      favorable anatomical success in cases of rhegmatogenous retinal detachment.

PMID- 22366902
TI  - Photodynamic therapy for symptomatic subretinal fluid related to choroidal nevus.
AB  - PURPOSE: The purpose of this article is to evaluate the role of photodynamic
      therapy (PDT) for symptomatic choroidal nevus with subretinal fluid (SRF)
      extending to the fovea. METHODS: Retrospective review of the medical records of
      all patients who underwent PDT for a symptomatic choroidal nevus with SRF.
      RESULTS: Seventeen patients were included in the study. The mean initial visual
      acuity was 20/80 (range, counting fingers to 20/20). The mean initial tumor
      thickness was 1.23 mm (range, 0.66-1.93 mm). All tumors presented at least 2 risk
      factors for growing (including orange pigment, symptoms, peripapillary location,
      SRF, and thickness >2 mm). The mean number of PDT sessions was 1.41 (range, 1-3).
      The mean final visual acuity improved to 20/60 (range, counting fingers to
      20/20). Subretinal fluid was reduced in all eyes (100%) and had completely
      disappeared in 9 eyes (53%) after PDT. Of 9 cases with complete resolution of the
      SRF, 2 patients (22%) presented recurrence. The mean final tumor thickness
      increased to 1.24 mm (range, 0.66-2.01 mm) at a mean follow-up of 22.47 months
      (range, 6-60 months). Tumor thickness increased in 3 eyes (18%) and remained
      unchanged in 13 eyes (76%), and 1 lesion (6%) shrank down to a flat chorioretinal
      scar. CONCLUSION: Photodynamic therapy is a good treatment option to reduce SRF
      in symptomatic choroidal nevus with serous macular detachment. Further growth
      into melanoma was observed in 18% of cases. Thus, PDT may not allow a good local
      tumor control. Longer follow-up is required to determine its value in these
      patients.

PMID- 22366903
TI  - Recurrent submacular hemorrhage in patients with neovascular age-related macular
      degeneration.
AB  - PURPOSE: To describe the incidence, risk factors for, and long-term visual
      outcomes of recurrent submacular hemorrhage in the context of age-related macular
      degeneration. METHODS: Medical records of patients with neovascular age-related
      macular degeneration with or without polypoidal choroidal vasculopathy showing
      submacular hemorrhage at their first visit to our institution were reviewed. The
      required minimum follow-up period was 24 months, and any newly developed
      submacular hemorrhage larger than 1 disk area after near-complete resolution of
      initial hemorrhage was defined as recurrence. RESULTS: A total of 47 eyes of 47
      patients were eligible for inclusion. Twenty-four patients showed recurrent
      submacular hemorrhage during the follow-up period (Group I). Patients without
      recurrent submacular hemorrhage were included in Group II. The time to recurrent
      submacular hemorrhage in Group I patients was 21.4 +/- 9.2 months. Polypoidal
      choroidal vasculopathy was present in 50% of Group I patients (n = 12) and 13% of
      Group II patients (n = 3) (P = 0.025). Intravitreal anti-vascular endothelial
      growth factor injection was performed during the follow-up period in 70.8% of
      Group I patients (n = 17) and 95.7% of Group II patients (n = 22) (P = 0.048).
      Visual acuity change during the follow-up period did not significantly differ
      between the two groups. CONCLUSION: In patients with neovascular age-related
      macular degeneration presenting with submacular hemorrhage at their first visit,
      the incidence of recurrent submacular hemorrhage was 51.1% in our retrospective
      long-term follow-up study. The presence of polypoidal choroidal vasculopathy was
      associated with an increased risk of recurrent submacular hemorrhage. Use of anti
      vascular endothelial growth factor agents was correlated with a reduced risk of
      such hemorrhage. Visual acuity was stably maintained over 2 years regardless of
      hemorrhage recurrence.

PMID- 22366904
TI  - Reduction of laser-induced choroidal neovascularization by intravitreal vasohibin
      1 in monkey eyes.
AB  - PURPOSE: To determine whether intravitreal vasohibin-1 will reduce the grade of
      the choroidal neovascularization in monkey eyes. METHODS: Choroidal
      neovascularizations were induced in 12 monkey eyes by laser photocoagulation.
      Three monkeys were evaluated for the safety of the vasohibin-1 injections, 6
      monkeys for the effects of a single injection, and 3 monkeys for repeated
      injections of vasohibin-1. Ophthalmoscopy, fluorescein angiography, focal
      electroretinograms, and optical coherence tomography were used for the
      evaluations. The level of vascular endothelial growth factor in the aqueous was
      determined by enzyme-linked immunosorbent assay. Immunohistochemistry was
      performed. RESULTS: An intravitreal injection of 10 MUg of vasohibin-1 induced
      mild intraocular inflammation. Eyes with an intravitreal injection of 0.1 MUg and
      1.0 MUg of vasohibin-1 had significant less fluorescein leakage from the
      choroidal neovascularizations and larger amplitude focal electroretinograms than
      that of vehicle-injected eyes. Similar results were obtained by repeated
      injections of 0.1 MUg of vasohibin-1. Immunohistochemistry showed that vasohibin
      1 was expressed mainly in the endothelial cells within the choroidal
      neovascularizations. The vascular endothelial growth factor level was not
      significantly altered by intravitreal vasohibin-1. CONCLUSION: The reduction of
      the laser-induced choroidal neovascularizations and preservation of macular
      function in monkey by intravitreal vasohibin-1 suggest that it should be
      considered for suppressing choroidal neovascularizations in humans.

PMID- 22366905
TI  - Vitreous hemorrhage after plaque radiotherapy for uveal melanoma.
AB  - PURPOSE: The purpose of this article is to determine the incidence, etiology,
      management, and outcome of vitreous hemorrhage (VH) after plaque radiotherapy for
      uveal melanoma. METHODS: Retrospective review of medical records. RESULTS: Of
      3,707 eyes treated with plaque radiotherapy for uveal melanoma, VH developed in
      4.1% at 1 year, 15.1% at 5 years, and 18.6% at 10 years by Kaplan-Meier analysis.
      Presumed causes of VH included tumor necrosis (29%), proliferative radiation
      retinopathy (24%), posterior vitreous detachment (16%), vascular occlusion (5%),
      and unknown (19%). Tumor necrosis was the most common cause of VH early in the
      follow-up period (3% at 1 year), while proliferative radiation retinopathy was
      the most common source of VH later (6.2% at 15 years). The most common initial
      management was conservative observation for resolution in 48%, laser
      photocoagulation in 24%, and vitrectomy in 18%. After a mean follow-up period of
      5 years, the VH was completely resolved in 41%, partially resolved in 19%,
      unresolved in 20%, worsened in 5%, and enucleation was necessary in 15%. By
      multivariable analysis, risk factors for development of VH were the presence of
      diabetic retinopathy at first visit (relative risk, 6.64), shorter tumor distance
      to the optic disc (relative risk, 1.07), greater initial tumor thickness
      (relative risk, 1.1), and break in the Bruch membrane (relative risk, 2.93). The
      rates of local tumor recurrence, extraocular extension, and distant metastasis in
      74 patients who underwent vitrectomy for VH removal after tumor regression were
      similar to those in patients who did not have vitrectomy for VH. CONCLUSION:
      Vitreous hemorrhage occurs after plaque radiotherapy for uveal melanoma in 15.1%
      of the patients by 5 years. The main factors predictive of VH included underlying
      diabetic retinopathy, closer tumor proximity to the disc, greater tumor
      thickness, and break in the Bruch membrane. After tumor regression, vitrectomy
      for blood removal appears to be safe.

PMID- 22366906
TI  - Incidence of retinal breaks in eyes undergoing 23-gauge or 20-gauge vitrectomy
      with induction of posterior vitreous detachment.
AB  - PURPOSE: To compare the incidence rates of retinal breaks in eyes in which
      posterior vitreous detachment was induced during 23-gauge and 20-gauge
      vitrectomies to treat macular holes or preretinal membranes. METHODS: We
      retrospectively reviewed 122 eyes of 115 patients with a macular hole or
      preretinal membrane who underwent induction of posterior vitreous detachment
      during 23-gauge vitrectomy (23-gauge group) and 61 eyes of 58 consecutive
      patients with the disorders who underwent induction of posterior vitreous
      detachment during 20-gauge vitrectomy performed by 1 surgeon. RESULTS: No
      difference was found in the incidence rates of intraoperative retinal breaks
      between the 23-gauge (16% [20/122]) and 20-gauge (16% [10/61]) groups. A
      postoperative rhegmatogenous retinal detachment developed in 2 (2%) eyes in the
      23-gauge group, whereas no eyes in the 20-gauge group had postoperative retinal
      breaks or rhegmatogenous retinal detachment. The incidence rates of retinal
      breaks in eyes with a macular hole and preretinal membrane did not differ
      significantly. CONCLUSION: Posterior vitreous detachment induced during
      vitrectomy frequently results in intraoperative retinal breaks, the incidence of
      which may be independent of the gauge of the vitreous instruments. Surgeons
      should be alert to the development of retinal breaks.

PMID- 22366909
TI  - Rotational diffusion and alignment of short gold nanorods in an external electric
      field.
AB  - We present measurements of the polarized extinction of gold nanorod suspensions
      exposed to an external electric field. By employing an amplitude modulated field
      in combination with lock-in detection we resolve changes in the optical density
      as low as 10(-6) in an integration time of 10 s. This sensitivity allows us to
      probe the partial alignment of small gold nanorods with an aspect ratio of 2.5
      and a width ranging from 13 nm to 28 nm. The degree of orientation scales as the
      square of the electric field strength, as expected for an induced dipole moment
      in an external field. By varying the modulation frequency we measure the rotation
      diffusion constant of different samples, which are in excellent agreement with
      the calculated values for a short cylinder.

PMID- 22366910
TI  - Understanding reduced activity in psychosis: the roles of stigma and illness
      appraisals.
AB  - PURPOSE: Increasing activity and social inclusion for people with psychosis is a
      primary goal of mental health services. Understanding the psychological
      mechanisms underlying reduced activity will inform more carefully targeted and
      effective interventions. Anxiety, depression, positive symptom distress and
      negative symptoms all make a contribution, but much of the variance in activity
      remains unaccounted for and is poorly understood. Appraisals of illness impact on
      adjustment to illness: mood, engagement in treatment and quality of life are all
      affected. It is plausible that illness appraisals will also influence activity.
      This study investigated the extent to which three components of illness appraisal
      accounted for variance in activity. METHOD: 50 people with psychosis completed
      measures of activity, positive and negative symptoms, anxiety and depression,
      cognitive functioning, stigma, insight and illness perceptions. RESULTS: Multiple
      regression revealed that internalised stigma, but not insight or illness
      perception, was significantly correlated with reduced activity. 42% of the
      variance in activity was accounted for by stigma, negative symptoms, positive
      symptom distress and social support. Affect, cognitive functioning and positive
      symptoms were not associated with activity. CONCLUSION: For people with
      psychosis, activity levels appear to be compromised particularly by fears of what
      others think of them and how they will be treated by others. Directly targeting
      these fears should improve the impact of psychological interventions on
      functioning. Specific, individualised cognitive behavioural interventions could
      be a useful adjunct to recovery-focused narrative therapies and complement public
      information campaigns to reduce discriminatory attitudes and behaviours.

PMID- 22366911
TI  - Suicidal communication signifies suicidal intent in Chinese completed suicides.
AB  - BACKGROUND: Recognizing suicidal communication from the distressful catharsis in
      a high-risk group with suicidal tendencies is essential for suicide prevention.
      This study analyzes whether suicidal communication can indicate the severity of
      suicidal intent. Various types of suicidal communication are defined, and their
      clinical significance is further explored. METHOD: A comprehensive analysis of
      the psychological autopsy data of 200 victims of completed suicide, including
      their general socio-demographic status, suicidal communication methods, previous
      suicide attempts, mental disorders, and psychosocial situation. RESULTS: Our
      results showed that 39.5% of all the subjects were suicidal communicators, 23.0%
      had previously attempted suicide, and 14.0% left suicide notes; 32.4% of 142
      subjects free of physical disease suffered from mental disorders. Suicidal
      communication included verbal communication, behavioral communication, and
      suicidal notes. Younger people with a higher level of education were more
      inclined to communicate their suicidal intent by leaving a suicide note. Suicide
      notes, but not previous suicide attempts or psychosocial situation, were
      significantly correlated with suicidal intent. Suicidal communicators showed
      higher depression scores than non-communicators. Those who suffered from mood
      disorders with higher levels of both depression and suicidal intent were more
      likely to expose their intent through behavioral communication. CONCLUSIONS: The
      present study provides strong evidence that suicidal communication can indicate
      the severity of suicidal intent. Current findings help interpret high-risk, self
      destructive behavior and consequently provide the theoretical basis for a
      feasible suicide prevention program.

PMID- 22366912
TI  - Enhanced isosteric heat of H2 adsorption by inclusion of crown ethers in a porous
      metal-organic framework.
AB  - Inclusion of 18-crown-6 or 15-crown-5 in a porous MOF increased the isosteric
      heats of H(2) adsorption significantly, which are comparable to MOFs containing
      open metal sites.

PMID- 22366913
TI  - Temperament and sensory features of children with autism.
AB  - This study sought to characterize temperament traits in a sample of children with
      autism spectrum disorder (ASD), ages 3-7 years old, and to determine the
      potential association between temperament and sensory features in ASD. Individual
      differences in sensory processing may form the basis for aspects of temperament
      and personality, and aberrations in sensory processing may inform why some
      temperamental traits are characteristic of specific clinical populations. Nine
      dimensions of temperament from the Behavioral Style Questionnaire (McDevitt and
      Carey in Manual for the behavioral style questionnaire, Behavioral-Developmental
      Initiatives, Scottsdale, AZ, 1996) were compared among groups of children with
      ASD (n = 54), developmentally delayed (DD; n = 33), and the original normative
      sample of typically developing children (McDevitt and Carey in J Child Psychol
      Psychiatr 19(3):245-253, 1978; n = 350) using an ANOVA to determine the extent to
      which groups differed in their temperament profiles. The hypothesized overlap
      between three sensory constructs (hyperresponsiveness, hyporesponsiveness, and
      seeking) and the nine dimensions of temperament was analyzed in children with ASD
      using regression analyses. The ASD group displayed temperament scores distinct
      from norms for typically developing children on most dimensions of temperament
      (activity, rhythmicity, adaptability, approach, distractibility, intensity,
      persistence, and threshold) but differed from the DD group on only two dimensions
      (approach and distractibility). Analyses of associations between sensory
      constructs and temperament dimensions found that sensory hyporesponsiveness was
      associated with slowness to adapt, low reactivity, and low distractibility; a
      combination of increased sensory features (across all three patterns) was
      associated with increased withdrawal and more negative mood. Although most
      dimensions of temperament distinguished children with ASD as a group, not all
      dimensions appear equally associated with sensory response patterns. Shared
      mechanisms underlying sensory responsiveness, temperament, and social withdrawal
      may be fruitful to explore in future studies.

PMID- 22366915
TI  - A new biomarker that predicts colonic neoplasia outcome in patients with
      hyperplastic colonic polyps.
AB  - The most frequently occurring lesions in the colon are the hyperplastic polyps.
      Hyperplastic polyps have long been considered as lesions with no malignant
      potential and colonoscopy for these patients is not recommended. However, recent
      works suggest that hyperplastic polyps may represent precursor lesions of some
      sporadic colorectal cancers. Until now, no biomarker allows to identify the
      subset of hyperplastic polyps that may have a malignant potential. Because the
      hormone precursor progastrin has been involved in colon carcinogenesis, we
      investigated whether its expression in hyperplastic polyps predicts the
      occurrence of colonic neoplasm after resection of hyperplastic polyps. We
      retrospectively analyzed progastrin expression in hyperplastic polyps from 74
      patients without history of colorectal pathology. In our study, 41% of patients
      presenting an initial hyperplastic polyp subsequently developed adenomatous
      polyps, recognized as precursor lesions for colorectal adenocarcinomas.
      Progastrin was overexpressed in the hyperplastic polyps in 40% of the patients.
      We showed a significant association between progastrin overexpression and
      shortened neoplasm-free survival (P = 0.001). Patients with high overexpression
      of progastrin had a 5-year neoplasm-free survival rate of 38% as compared with
      100% for the patients with low progastrin expression. In addition, we established
      a predictive test on the basis of progastrin staining and patients' age that
      predicts occurrence of neoplasm after developing a first hyperplastic polyp with
      a sensitivity of 100% [95% confidence interval (CI), 79%-100%] and a specificity
      of 74% (51%-90%). We show that progastrin expression evaluation in hyperplastic
      polyps is an efficient prognostic tool to determine patients with higher risk of
      metachronous neoplasms who could benefit from an adapted follow-up.

PMID- 22366914
TI  - delta- and gamma-tocopherols, but not alpha-tocopherol, inhibit colon
      carcinogenesis in azoxymethane-treated F344 rats.
AB  - The cancer preventive activity of vitamin E has been extensively discussed, but
      the activities of specific forms of tocopherols have not received sufficient
      attention. Herein, we compared the activities of delta-tocopherol (delta-T),
      gamma-T, and alpha-T in a colon carcinogenesis model. Male F344 rats, seven weeks
      old, were given two weekly subcutaneous injections of azoxymethane (AOM) each at
      a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the
      animals were maintained on a modified AIN76A diet, or the same diet containing
      0.2% of delta-T, gamma-T, alpha-T, or a gamma-T-rich mixture of tocopherols
      (gamma-TmT), until the termination of the experiment at 8 weeks after the second
      AOM injection. delta-T treatment showed the strongest inhibitory effect,
      decreasing the numbers of aberrant crypt foci by 62%. gamma-T and gamma-TmT were
      also effective, but alpha-T was not. Immunohistochemical analysis showed that
      delta-T and gamma-T treatments reduced the levels of 4-hydroxynonenal and
      nitrotyrosine and the expression of cyclin D1 in the colon, preserved the
      expression of PPAR-gamma, and decreased the serum levels of prostaglandin E2 and
      8-isoprostane. Supplementation with 0.2% delta-T, gamma-T, or alpha-T increased
      the respective levels of tocopherols and their side-chain degradation metabolites
      in the serum and colon tissues. Rather high concentrations of delta-T and gamma-T
      and their metabolites were found in colon tissues. Our study provides the first
      evidence for the much higher cancer preventive activity of delta-T and gamma-T
      than alpha-T in a chemically induced colon carcinogenesis model. It further
      suggests that delta-T is more effective than gamma-T.

PMID- 22366916
TI  - DTI parameters of axonal integrity and demyelination of the optic radiation
      correlate with glaucoma indices.
AB  - BACKGROUND: In glaucoma, damage of retinal ganglion cells may continue to the
      linked optic radiations. This study investigates the correlation of glaucoma
      severity indicators with parameters of axonal and myelin integrity of the optic
      radiations. METHODS: In this observational case-control study, 13 patients with
      normal-tension glaucoma, 13 patients with primary open-angle glaucoma, and seven
      control subjects (mean age, 57.6 +/- 12.5 years) were randomly selected for
      diffusion tensor imaging (DTI) of the optic radiations. The results of the
      frequency doubling test (FDT) and the HRT-based linear discriminant functions of
      Burk (BLDF) and Mikelberg (MLDF) were correlated with the mean of the fractional
      anisotropy (FA), apparent diffusion coefficient (ADC), and radial diffusivity
      (RD) of the optic radiations. Multiple correlation analysis, corrected for age,
      stage of cerebral microangiopathy, diagnosis group, and gender was conducted at
      increasing thresholds of linear anisotropy (C(L)) to reduce mismeasurements
      because of complex fiber situations. RESULTS: The best correlations were found
      for BLDF with FA at C(L) threshold 0.3 (0.594, p = 0.001), with ADC at C(L) 0.4 (
      0.511, p = 0.005), and with RD at C(L) 0.4 (-0.585, p = 0.001). MLDF correlated
      with FA at C(L) 0.4 (0.393, p = 0.035). The FDT score correlated with FA at C(L)
      0 (-0.491, p = 0.007) and with RD at C(L) 0 (-0.375, p = 0.045). CONCLUSIONS: In
      glaucoma, DTI-derived parameters of the axonal integrity (FA, ADC) and
      demyelination (RD) of the optic radiation are linked to HRT-based indices of
      glaucoma severity and to impairment of the spatial-temporal contrast sensitivity.

PMID- 22366917
TI  - Atypical cat scratch disease with vitritis, serous macular detachment,
      neuroretinitis, and retrobulbar optic neuritis.

PMID- 22366918
TI  - A balanced scorecard approach in assessing IT value in healthcare sector: an
      empirical examination.
AB  - Healthcare sector indicates human-based and knowledge-intensive property. Massive
      IT investments are necessary to maintain competitiveness in this sector. The
      justification of IT investments is the major concern of senior management.
      Empirical studies examining IT value have found inconclusive results with little
      or no improvement in productivity. Little research has been conducted in
      healthcare sector. The balanced scorecard (BSC) strikes a balance between
      financial and non-financial measure and has been applied in evaluating
      organization-based performance. Moreover, healthcare organizations often consider
      their performance goal at customer satisfaction in addition to financial
      performance. This research thus proposed a new hierarchical structure for the BSC
      with placing both finance and customer at the top, internal process at the next,
      and learning and growth at the bottom. Empirical examination has found the
      importance of the new BSC structure in assessing IT investments. Learning and
      growth plays the initial driver for reaching both customer and financial
      performance through the mediator of internal process. This can provide deep
      insight into effectively managing IT resources in the hospitals.

PMID- 22366919
TI  - Analysis of changes in farm pond network connectivity in the peri-urban landscape
      of the Taoyuan area, Taiwan.
AB  - The farm pond system for irrigation is the most prominent feature in the Taoyuan
      area, Taiwan, giving the region a unique landscape and hydrological character.
      Although this area had more than 3,290 ponds in the 1970s, fewer than 1,800 now
      remain. This study analyzes changes in irrigation farm ponds and the canal
      network landscape in the Taoyuan area. The spatial and temporal changes to ponds
      and the canal network on the Taoyuan plain were examined graphically for each
      spatial unit (2,765 m * 2,525 m) using aerial photographs for 1979 and 2005.
      Landscape metrics were calculated to analyze landscape change associated with
      increased urbanization. Landscape indices of connectivity and circuitry were
      utilized to describe changes in the configuration of ponds and canal networks.
      The total length of canals and total number of ponds in the study area decreased
      significantly during 1979-2005. The average values of connectivity indices (gamma
      and alpha-index) also decreased during 1979-2005, reflecting degradation of
      canal networks due to urban sprawl. A multivariate technique was applied to
      portion the study area into three zones according to changes to land cover,
      ponds, and canal networks. The effects of urban sprawl on the spatial pattern of
      ponds and canal networks are discussed.

PMID- 22366920
TI  - Nutrient interaction for optimal protein anabolism in resistance exercise.
AB  - PURPOSE OF REVIEW: The rapid muscle loss that accompanies varying diseased states
      (cachexia) is due to an imbalance between muscle protein synthesis (MPS) and
      muscle protein breakdown In the current review, we will discuss and summarize
      recent evidence in order to provide practical recommendations on exercise and
      nutrient interventions for cachectic populations. RECENT FINDINGS: Resistance
      exercise is a potent stimulus for MPS, but cachexia patients may not be best
      placed to lift the heavy loads that, it was previously assumed, were a
      prerequisite for muscle hypertrophy. However, recent evidence from our lab shows
      that lower loads can effectively stimulate MPS and lead to hypertrophy. Protein
      ingestion potentiates resistance exercise-induced rates of MPS. The source and
      dose of the ingested protein are important to consider when attempting to
      maximize postresistance exercise MPS. Specifically, rapidly digested, leucine
      rich protein sources may stimulate greater postexercise rates of MPS than other
      protein sources, as leucine acts as a key anabolic signal for mRNA translation.
      Furthermore, individuals undergoing relatively slow muscle atrophy (i.e., in
      sarcopenic elderly) respond positively to larger doses (40  g) of amino acids
      following exercise, whereas the response appears to plateau after moderate doses
      (20  g) in healthy, young adults. SUMMARY: Emerging evidence shows that
      manipulating traditional exercise loading and nutrient strategies may ameliorate
      cachexia.

PMID- 22366921
TI  - Do complementary feeding practices predict the later risk of obesity?
AB  - PURPOSE OF REVIEW: Obesity is a multifaceted public health problem, which should
      be addressed with an all-encompassing approach. Recent research has asked
      questions that link specific infant nutritional risks to childhood obesity. This
      article brings recent research in the area of complimentary feeding practices to
      light and summarizes the research on its consequent impact on obesity risk.
      RECENT FINDINGS: The article will discuss the current conflicting evidence on the
      relationship between the timing of introduction of complimentary foods and later
      obesity risk. It will summarize recent findings on the impact that complimentary
      feeding has on food preferences, growth and weight gain during the first year of
      life. SUMMARY: In industrialized countries complementary feeding has no major
      impact on obesity. However, there is some evidence that the age at introduction
      of complementary foods has some effect on growth in infancy and that effects
      might be more pronounced in formula-fed children. The focus of research should be
      shifted from the timing of the introduction of complementary feeding to the
      quality and quantity of foods being offered and their consequent impact on weight
      gain and obesity risk. More research should be conducted on the relationship of
      primary nutrition to appetite regulation, satiety and food acceptance.

PMID- 22366922
TI  - n-3 polyunsaturated fatty acids:  the potential role for supplementation in
      cancer.
AB  - PURPOSE OF REVIEW: n-3 polyunsaturated fatty acids, eicosapentaenoic acid and
      docosahexaenoic acid have been implicated as potential mediators in pathways
      involved in cancer cachexia. This review summarizes recent findings on the n-3
      fatty acid status of patients with cancer, the effects of n-3 fatty acid
      supplementation on weight and lean body mass and the potential role of
      supplementation during antineoplastic therapy. RECENT FINDINGS: Due to suboptimal
      intakes and possible metabolic disturbances, physiological concentrations of n-3
      fatty acids are low in patients with cancer. Low n-3 fatty acids are associated
      with loss of skeletal muscle, suggesting a need for supplementation. Recent
      trials have shown an effect of n-3 supplementation throughout antineoplastic
      therapy on weight, lean body mass and treatment outcomes. Attenuation or gain of
      weight and lean body mass was reported and the first clinical trials of n-3 fatty
      acids as an adjuvant to chemotherapy treatment suggest improved efficacy and
      milder treatment toxicity with n-3 fatty acid supplementation. SUMMARY: Recent
      evidence appears to favour providing n-3 fatty acids early in the disease
      trajectory, during antineoplastic therapy for preservation of muscle and also to
      improve treatment tolerance. Additional, larger trials are needed to define these
      relationships further but it appears that fish oil has broad therapeutic
      potential in patients with cancer.

PMID- 22366923
TI  - TWEAK and TRAF6 regulate skeletal muscle atrophy.
AB  - PURPOSE OF REVIEW: To discuss the roles and mechanisms of action of tumor
      necrosis factor-like weak inducer of apoptosis (TWEAK) and tumor necrosis factor
      receptor-associated factor 6 (TRAF6) in skeletal muscle atrophy. RECENT FINDINGS:
      Proinflammatory cytokines are known to mediate muscle atrophy in many chronic
      disease states. However, their role in the loss of skeletal muscle mass in disuse
      conditions has just begun to be elucidated. Further, the initial signaling events
      leading to the activation of various catabolic pathways in skeletal muscle under
      different atrophic conditions are also less well understood. The TWEAK-Fn14
      system has now been identified as a novel inducer of skeletal muscle wasting.
      Adult skeletal muscles express minimal levels of Fn14, the bona fide TWEAK
      receptor. Specific conditions of atrophy such as denervation, immobilization, or
      unloading rapidly induce the expression of Fn14 leading to TWEAK-induced
      activation of various proteolytic pathways in skeletal muscle. Recent studies
      have also demonstrated that the expression and activity of TRAF6 are increased in
      distinct models of muscle atrophy. Muscle-specific ablation of TRAF6 inhibits the
      induction of atrophy program in response to starvation, denervation, or cancer
      cachexia. Moreover, TWEAK also appears to activate some catabolic signaling
      through TRAF6-dependent mechanisms. SUMMARY: Recent findings have uncovered TWEAK
      and TRAF6 as novel regulators of skeletal muscle atrophy. These proteins should
      potentially be used as molecular targets for prevention and/or treatment of
      muscular atrophy in future therapies.

PMID- 22366924
TI  - Osteochondrosis dissecans of the tarsus in Labrador Retrievers: clinical signs,
      radiological data and force plate gait evaluation after surgical treatment.
AB  - OBJECTIVES: To report the outcome of unilateral surgery, by a plantaromedial
      approach, in 15 Labrador Retrievers with osteochondrosis dissecans (OCD) of the
      medial trochlear ridge of the talus. To evaluate the influence on outcome of age
      at surgery, bilateral involvement, periarticular soft tissue increase (PSI),
      osteophyte size (OS), decrease of range of joint motion and follow-up. To assess
      the extent of tarsal hyperextension in the standing dog. METHODS: A retrospective
      clinical and radiographic study was conducted and the post-treatment gait was
      analysed using a force plate. Ground reaction force (GRF) data were compared with
      data derived from 24 healthy Labrador Retrievers (control group). RESULTS: Six
      dogs had an excellent or good clinical result. Significant differences were found
      between the patients and the control group for many GRF data. Propulsive and
      vertical forces significantly decreased in the operated limb and increased in the
      contralateral pelvic and ipsilateral or both thoracic limbs. The lameness was
      significantly correlated to the OS postoperatively, the range-of-motion, the PSI,
      the length of the follow-up period, and the vertical ground force. No
      hyperextension in stance was recorded. CLINICAL SIGNIFICANCE: Although most dogs
      improved, the prognosis remains guarded. This seems to be independent of age,
      bilateral involvement, or preoperative OS in these dogs. No relation between
      medial talar OCD and tarsal hyperextension in stance was found in these dogs.

PMID- 22366925
TI  - Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane
      disease.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is characterized by
      crescentic glomerulonephritis with immunoglobulin G (IgG) autoantibodies to the
      non-collagenous (NC1) domain of alpha3(IV) collagen presenting along the GBM. The
      patient clinically manifests with rapidly progressive glomerulonephritis (RPGN)
      with pulmonary hemorrhage (Goodpasture syndrome). In rare cases, other
      immunocomplexes of IgA or IgM are involved, but their specificities have not been
      determined. We report a rare case of a 31-year-old female who was diagnosed as
      having anti-GBM disease with extensive IgA deposits in the mesangium. This
      patient presented heavy hematuria, proteinuria with increasing creatinine, but no
      lung hemorrhage. Renal biopsy showed crescentic glomerulonephritis (type I) with
      strong IgA (3+) as lump and branch shape. Therapies with pulse
      methylprednisolone, plasmapheresis and cyclophosphamide administration were less
      effective. This case is different from the present type I crescentic
      glomerulonephritis and the specificity of IgA deposits may implicate the
      pathogenesis of anti-GBM disease.

PMID- 22366926
TI  - The p85alpha regulatory subunit of PI3K mediates cAMP-PKA and retinoic acid
      biological effects on MCF7 cell growth and migration.
AB  - Phosphoinositide-3-OH kinase (PI3K) signalling regulates various cellular
      processes, including cell survival, growth, proliferation and motility, and is
      among the most frequently mutated pathways in cancer. Although the involvement of
      p85alphaPI3K SH2 domain in signal transduction has been extensively studied, the
      function of the SH3 domain at the N-terminus remains elusive. A serine (at codon
      83) adjacent to the N-terminal SH3 domain in the PI3K regulatory subunit
      p85alphaPI3K that is phosphorylated by protein kinase A (PKA) in vivo and in
      vitro has been identified. Virtually all receptors binding p85alphaPI3K can
      cooperate with cAMP-PKA signals via phosphorylation of p85alphaPI3KSer83. To
      analyse the role of p85alphaPI3KSer83 in retinoic acid (RA) and cAMP signalling,
      in MCF7 cells, we used p85alphaPI3K mutated forms, in which Ser83 has been
      substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid
      (p85D) to mimic the phosphorylated residue. We demonstrated that
      p85alphaPI3KSer83 is crucial for the synergistic enhancement of
      RARalpha/p85alphaPI3K binding induced by cAMP/RA co-treatment in MCF7 cells.
      Growth curves, colorimetric MTT assay and cell cycle analysis demonstrated that
      phosphorylation of p85alphaPI3KSer83 plays an important role in the control of
      MCF7 cell proliferation and in RA-induced inhibition of proliferation. Wound
      healing and transwell experiments demonstrated that p85alphaPI3KSer83 was also
      essential both for the control of migratory behaviour and for the reduction of
      motility induced by RA. This study points to p85alphaPI3KSer83 as the physical
      link between different pathways (cAMP-PKA, RA and FAK), and as an important
      regulator of MCF7 cell proliferation and migration.

PMID- 22366928
TI  - Rumen degradability characteristics of normal maize stover and silage, and
      quality protein maize silage-based diets offered to cows.
AB  - Rumen degradability characteristics of dry matter (DM), organic matter (OM) and
      crude protein (CP) of normal maize (NM) stover (T1)-, NM silage (T2)- and quality
      protein maize (QPM) silage (T3)-based diets were studied using three rumen
      fistulated Boran * Friesian non-lactating cows (371 +/- 32.00 kg) in 3 * 3 Latin
      Square Design. Cows were supplemented with a similar concentrate mix. In sacco
      degradability of DM and OM indicated that the (a) values of DM (128) and OM (114)
      for NM stover were lower (P < 0.001) than that for NM silage (268 and 253) and
      for QPM silage (323 and 303), respectively. The (a) value for CP was lower (P <
      0.05) for QPM silage (286) than for NM stover (404) and NM silage (326). The (b)
      values of DM in NM stover (597) and NM silage (535) were higher (P < 0.05) than
      in QPM silage (499). The (b) value of CP in NM stover (372) was lower (P < 0.05)
      than in NM silage (655) and in QPM silage (608). Rate of degradation of OM in NM
      stover and NM silage, each with 0.03, was faster (P < 0.01) than in QPM silage
      (0.02). Moreover, QPM silage had higher potentially degradable fraction for DM
      (821) (P < 0.05) and OM (840) (P < 0.01) than DM (725) and OM (712) in NM stover.
      The mean rumen ammonia concentration (209 mg/l) of QPM silage was higher (P <
      0.05) than that of NM stover (179 mg/l) and NM silage (170 mg/l). The average
      rumen pH (6.1) in cows fed QPM silage was lowest (P < 0.05) compared to pH (6.3)
      in cows fed either NM stover or silage. The concentration of total volatile fatty
      acids (116 mmol/l) in the rumen of cows incubated with QPM silage was higher (P <
      0.001) than in those incubated with NM stover (113 mmol/l) and NM silage (110
      mmol/l). It was concluded that QPM silage-based diet was superior in DM and OM
      degradability, and had higher ammonia and VFA concentration than NM stover-based
      diet. No differences have been observed in all parameters measured between QPM
      and NM silages.

PMID- 22366927
TI  - Metabolic activity in external and internal awareness networks in severely brain
      damaged patients.
AB  - OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal
      cortices) related to external/sensory awareness and an intrinsic midline network
      related to internal/self-awareness have been identified recently. This study
      measured brain metabolism in both networks in patients with severe brain damage.
      DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and
      Coma Recovery Scale-Revised assessments in a university hospital setting.
      SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive
      wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from
      MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were
      included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched
      controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks
      and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS
      showed impairment in posterior cingulate/retrosplenial cortices. LIS showed
      dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total
      scores correlated with metabolic activity in both extrinsic and part of the
      intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and
      intrinsic awareness network activity was observed in severely brain-damaged
      patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic
      network impairment in MCS could reflect altered internal/self-awareness in these
      patients, which is difficult to quantify at the bedside.

PMID- 22366929
TI  - [Physicians do not treat averages--but therapy responders!].

PMID- 22366930
TI  - [Undesired side effects of tapentadol in comparison to oxycodone. A meta-analysis
      of randomized controlled comparative studies].
AB  - OBJECTIVE: Tapentadol is a new centrally acting analgesic with a dual mode of
      action as an agonist of the u-opioid receptor and as a norepinephrine reuptake
      inhibitor. The aim of the present study was to evaluate the results from
      randomized controlled trials investigating the relative amount of adverse effects
      using tapentadol or oxycodone for the treatment of pain. METHODS: A quantitative
      systematic review was carried out according to the PRISMA recommendations on
      randomized controlled trials comparing tapentadol and oxycodone in pain
      treatment. The incidences of typical adverse side effects of opioid-based
      analgesic therapy (e.g. nausea, vomiting, obstipation or pruritus) were extracted
      and the pooled relative risks (RR) with corresponding 95% confidence intervals
      (CI) were calculated. RESULTS: A total of 9 trials involving 7,948 patients were
      included and of these 2,810 patients were treated with oxycodone and 5,138 were
      treated with tapentadol in equivalent analgesic dosages as documented by an
      equivalent analgesic effect. The risk of typical opioid-based adverse effects,
      such as nausea (RR 0.61; 95% CI 0.57-0.66), vomiting (RR 0.50, 95% CI: 0.41
      0.60), obstipation (RR 0.47, 95%-CI 0.40-0.56), dizziness (RR 0.86, 95% CI 0.78
      0.95), somnolence (RR 0.76, 95% CI 0.67-0.86) and pruritus (RR 0.46, 95% CI 0.37
      0.58) was reduced when tapentadol was used for analgesic treatment. These adverse
      effects were investigated in all nine trials. The risk for dryness of the mouth
      (6 trials, 6,218 patients, RR 1.79, 95% CI 1.40-2.29) and dyspepsia (1 trial, 646
      patients, RR 2.75, 95% CI 1.09-6.94) was increased when tapentadol was used
      instead of oxycodone. There were no significant differences in the relative risk
      for any other investigated adverse effect such as dysentery, headache or fatigue.
      CONCLUSION: The results show that using tapentadol significantly reduces the risk
      of the typical opioid-based adverse effects compared with oxycodone while
      providing equivalent analgesic treatment.

PMID- 22366931
TI  - [The pain situation for residents of nursing homes. Results of a study in
      Munster].
AB  - BACKGROUND: Little is known about the phenomenon of pain in German nursing homes.
      In particular, it is unknown to what extent and severity pain occurs among
      residents and how their pain can be described. MATERIAL AND METHODS: A total of
      13 nursing homes located in the city of Munster, Germany, were included as part
      of the health services research project "Action Alliance Pain-free City Munster."
      Data were collected from 436 residents over 65 years old via self-report or the
      observational pain tool pain assessment in advanced dementia, german version
      (PAINAD-G), according to the cognitive status of the residents. RESULTS: At the
      time of the interview, the majority of the residents questioned reported
      suffering from pain at rest and/or during movement. Approximately one quarter of
      residents complained about moderate to intolerable pain at rest and nearly 45%
      during movement. Residents encountered pain most often when standing up, sitting,
      resting in bed and walking and three quarters of residents had suffered from pain
      for more than 1 year. Many residents experienced pain in several body regions.
      Among residents assessed solely by the observational pain scale PAINAD-G, signs
      indicating pain existed in 21% (>= 6) or 69% (>= 2), respectively, depending on
      the cut-off value chosen on the PAINAD-G scale. CONCLUSION: Pain in nursing homes
      is a challenge that needs more attention as it has considerable negative
      consequences for the persons concerned. The extent of pain in the studied
      facilities indicates an urgent need for action on the part of all professionals
      caring for residents in nursing homes.

PMID- 22366932
TI  - [Is there a correlation between back pain and stability of the lumbar spine in
      pregnancy? A model-based hypothesis].
AB  - During pregnancy approximately 50% of women suffer from low back pain (LBP),
      which significantly affects their everyday life. The pain could result in chronic
      insomnia, limit the pregnant women in their ability to work and produce a
      reduction of their physical activity. The etiology of the pain is still
      critically discussed and not entirely understood. In the literature different
      explanations for LBP are given and one of the most common reasons is the
      anatomical changes of the female body during pregnancy; for instance, there is an
      increase in the sagittal moments because of the enlarged uterus and fetus and the
      occurrence of hyperlordosis.The aim of this study was to describe how the
      anatomical changes in pregnant women affect the stability and the moments acting
      on the lumbar spine with the help of a simplified musculoskeletal model.A two
      dimensional musculoskeletal model of the lumbar spine in the sagittal plane
      consisting of five lumbar vertebrae was developed. The model included five
      centres of rotation and three antagonistic pairs of paraspinal muscles. The
      concept of altered acting torques during pregnancy was explored by varying the
      geometrical arrangements. The situations non-pregnant, pregnant and pregnant with
      hyperlordosis were considered for the model-based approach. These simulations
      were done dependent on the stability of the erect posture and local
      countertorques of every lumbar segment.In spite of the simplicity of the model
      and the musculoskeletal arrangement it was possible to maintain equilibrium of
      the erect posture at every lumbar spinal segment with one minimum physiological
      cross-sectional area of all paraspinal muscles. The stability of the
      musculoskeletal system depends on the muscular activity of the paraspinal muscles
      and diminishing the muscular activity causes unstable lumbar segments.The
      relationship between the non-pregnant and the pregnant simulations demonstrated a
      considerable increase of acting segmental countertorques. Simulating an increased
      lordosis for the pregnant situation in the sagittal plane substantially reduced
      these acting countertorques and therefore the demand on the segmental muscles.It
      is assumed that hyperlordosis is a physiological adaptation to the anatomical
      changes during pregnancy to minimize the segmental countertorques and therefore
      the demand on the segmental muscles.Further, it can be expected that an enhanced
      muscle activity caused by selective activity of lumbar muscles increases the
      stability of the lumbar spine and may improve the situation with LBP during
      pregnancy.

PMID- 22366934
TI  - [Restrictions in participation in women with fibromyalgia syndrome. An
      explorative pilot study].
AB  - BACKGROUND: Patients with fibromyalgia syndrome are often severely restricted in
      their ability to participate in everyday activities and in social interaction.
      The aim of this study was to document female patients' subjectively-perceived
      limitations in participation and to develop material to generate items for a
      specific participation questionnaire. MATERIAL AND METHODS: We collected data
      from 8 groups of women with fibromyalgia syndrome (n=38), and developed a
      hierarchical system of categories using the patients' statements (ATLAS.ti;
      Qualitative Data Analysis). RESULTS: Our final group of categories contains 10
      superordinate categories. Women with fibromyalgia syndrome often describe
      restrictions in their relationships with other people, and the impaired ability
      to engage in social and leisure activities. They speak of difficulties at the
      workplace, while doing housework, and complain about a lack of understanding and
      awareness on the part of the general public. CONCLUSION: Fibromyalgia syndrome
      patients admit to be extremely impaired in a variety of social roles. Their
      statements have enabled us to develop a questionnaire that reflects the range of
      factors restricting participation from the patient's perspective.

PMID- 22366935
TI  - [Communication preferences of patients with chronic back pain in medical
      rehabilitation].
AB  - BACKGROUND: Successful treatment of chronic pain patients can be dependent on
      successful patient-provider communication. Patient-physician communication for
      patients with chronic back pain (CBP) has rarely been explored. The current study
      examines two questions: what is important for CBP patients concerning
      communication with the healthcare provider and are there interindividual
      differences in communication preferences dependent on sociodemographic
      characteristics? METHODS: Patient preferences were measured using the KOPRA
      questionnaire (32 items and 4 scales). The mean age of the 701 participating
      rehabilitants was 51 years (SD +/-11.1 years) of which 60% were women. RESULTS:
      An effective and open communication with the healthcare physician was rated as
      the most important preference for CBP patients. Gender (depending on the scale: p
      = 0.01-0.82) and age (p = 0.01-0.12) seemed to influence some preferences in
      patient-provider communication. CONCLUSION: By taking into account individual
      communication preferences of CBP patients, healthcare providers could
      purposefully be responsive to these, possibly contributing to a more successful
      treatment.

PMID- 22366936
TI  - [Chronic musculoskeletal pain syndrome in primary hyperparathyroidism].
AB  - Chronic somatic pain disorders with somatic and mental factors (ICD-10: F45.41)
      are common among psychosomatic patients. In the present case, due to the close
      temporal association with a trauma and the subsequent development of symptoms
      including depressive symptoms, a chronic pain disorder with a relevant somatoform
      component was suspected. However, after a period of several months without
      significant somatic findings, targeted diagnostic approaches resulted in the
      diagnoses of primary hyperparathyroidism and a papillary thyroid carcinoma.
      Surgical therapy resulted in an almost complete decline of symptoms within a
      short period of time.

PMID- 22366937
TI  - [Lifting capacity with low back pain].

PMID- 22366938
TI  - [Cancer-related fatigue and its psychosocial burden].
AB  - Cancer-related fatigue (CRF) is a highly prevalent and the most distressing
      symptom during and after treatment for cancer. It is characterized by feelings of
      physical and mental tiredness, weakness, and lack of energy and is not influenced
      by rest or sleep. Approximately 40% of patients suffer from CRF at diagnosis and
      nearly all patients experience fatigue during the course of cancer therapy. The
      impact of CRF on daily living and patient quality of life (QoL) is substantial.
      It profoundly affects patient quality of life and limits personal, social and
      occupational roles. The fatigue is also associated with significant levels of
      distress and it imposes a financial burden by limiting the ability to work. The
      underlying causes of CRF are poorly understood as are the relationship between
      fatigue and psychosocial distress, depression or anxiety. This paper seeks to
      give an overview of cancer-related fatigue and its psychosocial burden.

PMID- 22366943
TI  - Infections in surgery of primary tumors of the sacrum.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the risk of
      infection, related treatment, and outcome after surgery of the 2 most common
      primary sacral tumors. SUMMARY OF BACKGROUND DATA: Rarity of sacral tumors has
      limited the number of population-based studies. Treatment depends on malignancy
      or local aggressiveness: wide resection is indicated for malignant lesions,
      intralesional surgery for benign. METHODS: We studied 82 patients with sacral
      chordomas (55 cases) or giant cell tumor (GCT) (27 cases) treated between 1976
      and 2005. All patients had IV antibiotic therapy with amikacin and teicoplanin.
      Surgery of chordoma was resection; surgery of GCT was intralesional excision.
      Infections were classified as immediate postoperative, early (within 6 months),
      and late (more than 6 months from surgery). Mean follow-up was 9.5 years (range:
      3-27 years). Some factors possibly influencing the risk of infection were
      statistically analyzed by Kaplan Meier curves and log-rank test. RESULTS: No deep
      infections were observed in the GCT series. Three patients with sacral chordoma
      died for postoperative complications and were excluded from this analysis. Of the
      remaining 52 patients with chordoma, 23/52 had deep wound infection (44%) that
      required 1 or more surgical debridements combined with antibiotics, according to
      cultures. In 16 patients (70%), infection occurred within 4 weeks
      postoperatively, and in 7 within 6 months. Most frequent bacteria were
      Enterococcus (23%), Escherichia coli (20%), and Pseudomonas aeruginosa (18%). In
      74% of cases, infection was multimicrobial. Level of resection, previous
      intralesional treatment elsewhere, tumor volume, and age did not statistically
      influence risk of infection. CONCLUSION: Type of surgery was the prominent factor
      related to a major risk of infection. Operating procedure time correlated as
      well. Resections of sacral chordoma imply a high risk of deep infection, while
      intralesional excision of GCT does not. All infections healed with surgical
      debridements and antibiotic therapy.

PMID- 22366944
TI  - Re: Rajasekaran S, Natarajan RN, Babu JN, et al. Lumbar vertebral growth is
      governed by "chondral growth force response curve" rather than "Hueter-Volkmann
      law": a clinico-biomechanical study of growth modulation changes in childhood
      spinal tuberculosis. Spine 2011;36:E1435-45.

PMID- 22366945
TI  - Pedicle subtraction osteotomy in the cervical spine.
AB  - STUDY DESIGN: Description of surgical technique with review of literature.
      OBJECTIVE: To describe the surgical management of cervical spine deformity, using
      pedicle subtraction osteotomy. SUMMARY OF BACKGROUND DATA: Previous articles have
      primarily described Smith-Petersen osteotomies and Simmons' modifications to
      correct fixed cervical deformity. Those were typically performed with the patient
      awake and sedated in a seated position and without the use of spinal
      instrumentation. METHODS: Description of a single surgeon's technique for
      performing pedicle subtraction osteotomy to treat fixed cervical deformity.
      CONCLUSION: The use of pedicle subtraction osteotomy in the cervical spine is a
      safe and effective procedure when performed by experienced surgeons and can
      result in a satisfying outcome for both the patient and the surgeon.

PMID- 22366947
TI  - Impairments in static standing balance are highly prevalent among older adults
      receiving home-based physical therapy.
AB  - BACKGROUND AND PURPOSE: Measures of balance are an important component of the
      physical therapist examination. This study investigated the usefulness of timed
      static stance durations for identifying balance impairments among patients
      receiving home-based physical therapy. METHODS: This study involved the
      retrospective retrieval of data from the records of 48 patients at least 60 years
      of age. Their balance was measured under 3 foot configurations; that is, feet
      apart, feet together, and on each foot. RESULTS: Every patient demonstrated
      impaired standing balance. Most, but not all could balance 30 seconds with the
      feet apart or together. Only 19 could maintain balance on each of both feet. Of
      those who could so balance, none was able to achieve the average time of normal
      individuals of comparable age. DISCUSSION AND CONCLUSIONS: Although not able to
      identify all aspects of balance, timed durations of stance under different
      configurations demonstrate a high prevalence of balance impairments among
      patients receiving home-based physical therapy. As the tests are objective, fast,
      and require little space, they can be advocated in such a setting.

PMID- 22366948
TI  - Oocyte formation by mitotically active germ cells purified from ovaries of
      reproductive-age women.
AB  - Germline stem cells that produce oocytes in vitro and fertilization-competent
      eggs in vivo have been identified in and isolated from adult mouse ovaries. Here
      we describe and validate a fluorescence-activated cell sorting-based protocol
      that can be used with adult mouse ovaries and human ovarian cortical tissue to
      purify rare mitotically active cells that have a gene expression profile that is
      consistent with primitive germ cells. Once established in vitro, these cells can
      be expanded for months and can spontaneously generate 35- to 50-MUm oocytes, as
      determined by morphology, gene expression and haploid (1n) status. Injection of
      the human germline cells, engineered to stably express GFP, into human ovarian
      cortical biopsies leads to formation of follicles containing GFP-positive oocytes
      1-2 weeks after xenotransplantation into immunodeficient female mice. Thus,
      ovaries of reproductive-age women, similar to adult mice, possess rare
      mitotically active germ cells that can be propagated in vitro as well as generate
      oocytes in vitro and in vivo.

PMID- 22366949
TI  - Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as
      tumor suppressor in T-ALL.
AB  - The TLX1 and TLX3 transcription factor oncogenes have a key role in the
      pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse
      engineering of global transcriptional networks to decipher the oncogenic
      regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis
      defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an
      oncogenic transcriptional circuit governing T-ALL. Notably, a network structure
      analysis of this hierarchical network identified RUNX1 as a key mediator of the T
      ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T
      cell transformation. Consistent with these results, we identified recurrent
      somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these
      results place TLX1 and TLX3 at the top of an oncogenic transcriptional network
      controlling leukemia development, show the power of network analyses to identify
      key elements in the regulatory circuits governing human cancer and identify RUNX1
      as a tumor-suppressor gene in T-ALL.

PMID- 22366950
TI  - NKG2D signaling on CD8+ T cells represses T-bet and rescues CD4-unhelped CD8+ T
      cell memory recall but not effector responses.
AB  - CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the
      absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer
      group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability
      to rescue these immunologically impotent cells. We demonstrate that augmented co
      stimulation through NKG2D during priming paradoxically rescues memory, but not
      effector, CD8(+) T cell responses. NKG2D-mediated rescue is characterized by
      reversal of elevated transcription factor T-box expressed in T cells (T-bet)
      expression and recovery of interleukin-2 and interferon-gamma production and
      cytolytic responses. Rescue is abrogated in CD8(+) T cells lacking NKG2D.
      Augmented co-stimulation through NKG2D confers a high rate of survival to mice
      lacking CD4(+) T cells in a CD4-dependent influenza model and rescues HIV
      specific CD8(+) T cell responses from CD4-deficient HIV-positive donors. These
      findings demonstrate that augmented co-stimulation through NKG2D is effective in
      rescuing CD4-unhelped CD8(+) T cells from their pathophysiological fate and may
      provide therapeutic benefits.

PMID- 22366953
TI  - Luminescent coordination polymer gels based on rigid terpyridyl phosphine and
      Ag(I).
AB  - Rigid bridging terpyridyl phosphine and AgOTf form nanofibres to induce gelation
      of organic solvents, and the gel emits blue luminescence by suppressing pi-pi
      interactions between ligands.

PMID- 22366951
TI  - Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for
      cell tracking by magnetic resonance imaging.
AB  - We report on a new straightforward magnetic cell-labeling approach that combines
      three US Food and Drug Administration (FDA)-approved drugs--ferumoxytol, heparin
      and protamine--in serum-free medium to form self-assembling nanocomplexes that
      effectively label cells for in vivo magnetic resonance imaging (MRI). We observed
      that the ferumoxytol-heparin-protamine (HPF) nanocomplexes were stable in serum
      free cell culture medium. HPF nanocomplexes show a threefold increase in T2
      relaxivity compared to ferumoxytol. Electron microscopy showed internalized HPF
      in endosomes, which we confirmed by Prussian blue staining of labeled cells.
      There was no long-term effect or toxicity on cellular physiology or function of
      HPF-labeled hematopoietic stem cells, bone marrow stromal cells, neural stem
      cells or T cells when compared to controls. In vivo MRI detected 1,000 HPF
      labeled cells implanted in rat brains. This HPF labeling method should facilitate
      the monitoring by MRI of infused or implanted cells in clinical trials.

PMID- 22366952
TI  - High abundance of plasma cells secreting transglutaminase 2-specific IgA
      autoantibodies with limited somatic hypermutation in celiac disease intestinal
      lesions.
AB  - Celiac disease is an immune-mediated disorder in which mucosal autoantibodies to
      the enzyme transglutaminase 2 (TG2) are generated in response to the exogenous
      antigen gluten in individuals who express human leukocyte antigen HLA-DQ2 or HLA
      DQ8 (ref. 3). We assessed in a comprehensive and nonbiased manner the IgA anti
      TG2 response by expression cloning of the antibody repertoire of ex vivo-isolated
      intestinal antibody-secreting cells (ASCs). We found that TG2-specific plasma
      cells are markedly expanded within the duodenal mucosa in individuals with active
      celiac disease. TG2-specific antibodies were of high affinity yet showed little
      adaptation by somatic mutations. Unlike infection-induced peripheral blood
      plasmablasts, the TG2-specific ASCs had not recently proliferated and were not
      short-lived ex vivo. Altogether, these observations demonstrate that there is a
      germline repertoire with high affinity for TG2 that may favor massive generation
      of autoreactive B cells. TG2-specific antibodies did not block enzymatic activity
      and served as substrates for TG2-mediated crosslinking when expressed as IgD or
      IgM but not as IgA1 or IgG1. This could result in preferential recruitment of
      plasma cells from naive IgD- and IgM-expressing B cells, thus possibly explaining
      why the antibody response to TG2 bears signs of a primary immune response despite
      the disease chronicity.

PMID- 22366954
TI  - Force-field and quantum-mechanical binding study of selected SAMPL3 host-guest
      complexes.
AB  - A Merck molecular force field classical potential combined with Poisson-Boltzmann
      electrostatics (MMFF/PB) has been used to estimate the binding free energy of
      seven guest molecules (six tertiary amines and one primary amine) into a
      synthetic receptor (acyclic cucurbit[4]uril congener) and two benzimidazoles into
      cyclic cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) hosts. In addition,
      binding enthalpies for the benzimidazoles were calculated with density functional
      theory (DFT) using the B3LYP functional and a polarizable continuum model (PCM).
      Although in most cases the MMFF/PB approach returned reasonable agreements with
      the experiment (+/-2 kcal/mol), significant, much larger deviations were reported
      in the case of three host-guest pairs. All four binding enthalpy predictions with
      the DFT/PCM method suffered 70% or larger deviations from the calorimetry data.
      Results are discussed in terms of the molecular models used for guest-host
      complexation and the quality of the intermolecular potentials.

PMID- 22366955
TI  - Blind prediction of host-guest binding affinities: a new SAMPL3 challenge.
AB  - The computational prediction of protein-ligand binding affinities is of central
      interest in early-stage drug-discovery, and there is a widely recognized need for
      improved methods. Low molecular weight receptors and their ligands--i.e., host
      guest systems--represent valuable test-beds for such affinity prediction methods,
      because their small size makes for fast calculations and relatively facile
      numerical convergence. The SAMPL3 community exercise included the first ever
      blind prediction challenge for host-guest binding affinities, through the
      incorporation of 11 new host-guest complexes. Ten participating research groups
      addressed this challenge with a variety of approaches. Statistical assessment
      indicates that, although most methods performed well at predicting some general
      trends in binding affinity, overall accuracy was not high, as all the methods
      suffered from either poor correlation or high RMS errors or both. There was no
      clear advantage in using explicit versus implicit solvent models, any particular
      force field, or any particular approach to conformational sampling. In a few
      cases, predictions using very similar energy models but different sampling and/or
      free-energy methods resulted in significantly different results. The protonation
      states of one host and some guest molecules emerged as key uncertainties beyond
      the choice of computational approach. The present results have implications for
      methods development and future blind prediction exercises.

PMID- 22366956
TI  - An interview with Phil Bourne, associate director of the RCSB protein data bank.

PMID- 22366958
TI  - Myelination in coculture of established neuronal and Schwann cell lines.
AB  - Establishing stable coculture systems with neuronal and Schwann cell lines has
      been considered difficult, presumably because of their high proliferative
      activity and phenotypic differences from primary cultured cells. The present
      study is aimed at developing methods for myelin formation under coculture of the
      neural crest-derived pheochromocytoma cell line PC12 and the immortalized adult
      rat Schwann cell line IFRS1. Prior to coculture, PC12 cells were seeded at low
      density (3 * 10(2)/cm(2)) and maintained in serum-free medium with N2 supplement,
      ascorbic acid (50 MUg/ml), and nerve growth factor (NGF) (50 ng/ml) for a week.
      Exposure to such a NGF-rich environment with minimum nutrients accelerated
      differentiation and neurite extension, but not proliferation, of PC12 cells. When
      IFRS1 cells were added to NGF-primed PC12 cells, the cell density ratio of PC12
      cells to IFRS1 cells was adjusted from 1:50 to 1:100. The cocultured cells were
      then maintained in serum-free medium with B27 supplement, ascorbic acid (50
      MUg/ml), NGF (10 ng/ml), and recombinant soluble neuregulin-1 type III (25
      ng/ml). Myelin formation was illustrated by light and electron microscopy
      performed at day 28 of coculture. The stable PC12-IFRS1 coculture system is free
      of technical and ethical problems arising from the primary culture and can be a
      valuable tool to study peripheral nerve degeneration and regeneration.

PMID- 22366959
TI  - Pre-analytical effects of blood sampling and handling in quantitative
      immunoassays for rheumatoid arthritis.
AB  - Variability in pre-analytical blood sampling and handling can significantly
      impact results obtained in quantitative immunoassays. Understanding the impact of
      these variables is critical for accurate quantification and validation of
      biomarker measurements. Particularly, in the design and execution of large
      clinical trials, even small differences in sample processing and handling can
      have dramatic effects in analytical reliability, results interpretation, trial
      management and outcome. The effects of two common blood sampling methods (serum
      vs. plasma) and two widely-used serum handling methods (on the clot with ambient
      temperature shipping, "traditional", vs. centrifuged with cold chain shipping,
      "protocol") on protein and autoantibody concentrations were examined. Matched
      serum and plasma samples were collected from 32 rheumatoid arthritis (RA)
      patients representing a wide range of disease activity status. Additionally, a
      set of matched serum samples with two sample handling methods was collected. One
      tube was processed per manufacturer's instructions and shipped overnight on cold
      packs (protocol). The matched tube, without prior centrifugation, was
      simultaneously shipped overnight at ambient temperatures (traditional). Upon
      delivery, the traditional tube was centrifuged. All samples were subsequently
      aliquoted and frozen prior to analysis of protein and autoantibody biomarkers.
      Median correlation between paired serum and plasma across all autoantibody assays
      was 0.99 (0.98-1.00) with a median % difference of -3.3 (-7.5 to 6.0). In
      contrast, observed protein biomarker concentrations were significantly affected
      by sample types, with median correlation of 0.99 (0.33-1.00) and a median %
      difference of -10 (-55 to 23). When the two serum collection/handling methods
      were compared, the median correlation between paired samples for autoantibodies
      was 0.99 (0.91-1.00) with a median difference of 4%. In contrast, significant
      increases were observed in protein biomarker concentrations among certain
      biomarkers in samples processed with the 'traditional' method. Autoantibody
      quantification appears robust to both sample type (plasma vs. serum) and pre
      analytical sample collection/handling methods (protocol vs. traditional). In
      contrast, for non-antibody protein biomarker concentrations, sample type had a
      significant impact; plasma samples generally exhibit decreased protein biomarker
      concentrations relative to serum. Similarly, sample handling significantly
      impacted the variability of protein biomarker concentrations. When biomarker
      concentrations are combined algorithmically into a single test score such as a
      multi-biomarker disease activity test for rheumatoid arthritis (MBDA), changes in
      protein biomarker concentrations may result in a bias of the score. These results
      illustrate the importance of characterizing pre-analytical methodology, sample
      type, sample processing and handling procedures for clinical testing in order to
      ensure test accuracy.

PMID- 22366961
TI  - microRNA expression profile and differentially-expressed genes in prolactinomas
      following bromocriptine treatment.
AB  - Little is known about the function of microRNAs in prolactinomas treated with
      bromocriptine. The aim of the study was to explore the microRNAs associated with
      bromocriptine-treated prolactinomas. Six prolactinoma samples were selected
      according to whether they received bromocriptine treatment or not before
      microsurgery, and microRNA expression profiles of bromocriptine-treated and
      untreated prolactinomas were screened by the miRCURY LNA Array. The
      differentially expressed microRNAs in microarrays were further validated by stem
      loop real-time PCR and subjected to gene ontology analysis and KEGG pathway
      analysis. In addition, related genes of microRNAs were analyzed by qRT-PCR in 15
      prolactinoma samples. The initial analysis by microarrays generated a list of 80
      upregulated microRNAs and 71 downregulated microRNAs in treated prolactinomas
      compared to untreated prolactinomas. miR-206, miR-516b and miR-550 were confirmed
      to be significantly upregulated, while miR-671-5p was confirmed to be
      significantly downregulated in treated prolactinomas by qRT-PCR. microRNA-mRNA
      network analysis integrating GO and KEGG pathway annotation displayed some
      critical factors. Platelet-derived growth factor alpha polypeptide (PDGFA) and
      bone morphogenetic protein 4 (BMP4), were verified to be differentially expressed
      between the two groups. PDGFA was significantly upregulated in treated
      prolactinomas, while BMP4 was significantly downregulated in treated
      prolactinomas. Our study reveals differential expression of microRNAs in
      prolactinoma after pharmacotherapy. Specific microRNAs may be involved in the
      inhibition or promotion of prolactinoma tumor growth impacted by bromocriptine
      pharmacotherapy. PDGFA and BMP4 may be involved in the pharmacotherapy mechanism
      of prolactinoma.

PMID- 22366963
TI  - Healing of patellar fractures in two kittens.
AB  - Two kittens aged between four and five months were presented having sustained
      patellar fractures. In both cases, healing was subsequently documented
      radiographically; this has not been reported previously in the literature.  One
      kitten had bilateral patellar fractures - the symptomatic right stifle was
      treated with a pin and tension-band-wire which later failed, at which point
      partial patellectomy was performed. The fracture of the left patella was
      minimally displaced and was treated conservatively. A radiograph of the left
      patella taken eleven months after initial presentation showed complete healing of
      the fracture. The second case was treated surgically with a circumferential wire;
      healing of the fracture was demonstrated radiographically at twelve weeks
      postoperatively. Radiographic images taken five weeks postoperatively had shown
      some narrowing of the fracture gap. These two cases demonstrate that bony union
      of patellar fractures can be documented, given a long enough duration of
      radiographic follow-up; circumferential wire was an effective treatment in a
      displaced fracture, and conservative treatment resulted in complete healing of a
      minimally displaced fracture.

PMID- 22366962
TI  - Mechanism of meningeal invasion by Neisseria meningitidis.
AB  - The blood-cerebrospinal fluid barrier physiologically protects the meningeal
      spaces from blood-borne bacterial pathogens, due to the existence of specialized
      junctional interendothelial complexes. Few bacterial pathogens are able to reach
      the subarachnoidal space and among those, Neisseria meningitidis is the one that
      achieves this task the most constantly when present in the bloodstream. Meningeal
      invasion is a consequence of a tight interaction of meningococci with brain
      endothelial cells. This interaction, mediated by the type IV pili, is responsible
      for the formation of microcolonies on the apical surface of the cells. This
      interaction is followed by the activation of signaling pathways in the host cells
      leading to the formation of endothelial docking structures resembling those
      elicited by the interaction of leukocytes with endothelial cells during
      extravasation. The consequence of these bacterial-induced signaling events is the
      recruitment of intercellular junction components in the docking structure and the
      subsequent opening of the intercellular junctions.

PMID- 22366964
TI  - Sperm DNA damage:  how relevant is it clinically?
AB  - PURPOSE OF REVIEW: The true impact of the current sperm DNA fragmentation testing
      needs further scrutiny to assess whether clinically meaningful information is
      conveyed. RECENT FINDINGS: Various studies have suggested different or no
      threshold values with assorted tests for the percentage of DNA fragmentation in
      the ejaculated sperm above which natural conception, fertilization or embryo
      development and/or clinical pregnancy rates are compromised. Current DNA
      fragmentation assessment methods provide very little specific information on the
      nature and severity of the DNA damage detected. Although sperm DNA fragmentation
      is associated with lower pregnancy rates through natural conception or
      intrauterine insemination, it does not seem to affect intracytoplasmic sperm
      injection outcome. Although animal studies demonstrated adverse reproductive
      effects of sperm DNA fragmentation, any conclusive evidence in humans is yet to
      be demonstrated. It is not clear whether interventions aimed at enrichment of
      sperm with decreased DNA fragmentation are effective in preventing the potential
      adverse effects of sperm DNA fragmentation in humans. Major concern about the use
      of sperm DNA integrity tests as prognostic parameters is that the direct
      evaluation of DNA fragmentation in individual sperm fertilizing the oocyte is not
      possible. SUMMARY: The lack of consensus in defining a clinically relevant
      standard DNA fragmentation test with a meaningful cut-off level brings challenges
      in implementing the routine use of sperm DNA integrity assessment in daily
      practice.

PMID- 22366965
TI  - The global landscape of cross-border reproductive care:  twenty key findings for
      the new millennium.
AB  - PURPOSE OF REVIEW: Cross-border reproductive care (CBRC), also known as
      procreative tourism, fertility tourism, or reproductive tourism, is an increasing
      global phenomenon. This article reviews the expanding scholarly literature on
      CBRC, with 2010-2011 representing watershed years for CBRC scholarship and
      activism. RECENT FINDINGS: Terminological debates, missing data, and lack of
      international monitoring plague the study of CBRC. Nonetheless, it is widely
      acknowledged that CBRC is a growing industry, with new global hubs, new
      intermediaries, new media, and new spaces of interaction. Religious bans and
      legal restrictions have created a patchwork of 'restrictive' and 'permissive'
      countries, with law evasion being a primary driver of CBRC. Yet, patient
      motivations for CBRC are diverse and patients' levels of satisfaction with CBRC
      and its outcomes are generally high. Thus, scholarly concern with CBRC as law
      evasion must be tempered with qualitative studies of positive patient
      experiences. SUMMARY: CBRC can be considered a form of 'global gynecology' in
      which reproductive medicine, tourism, and commerce are converging in the second
      decade of the new millennium.

PMID- 22366966
TI  - Anterior cervical reconstruction with pedicle screws after a 4-level corpectomy.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a new method of anterior
      cervical reconstruction with pedicle screws. SUMMARY OF BACKGROUND DATA: Anterior
      reconstruction after multilevel corpectomy is a challenging technique, and there
      are many reports on its complications. Graft dislodgement is one of the major
      complications after long cervical fusion. The main cause of failure seems to be a
      lack of stability in the conventional reconstruction technique. However, pedicle
      screws for posterior cervical reconstruction show remarkable stability. We
      describe a new technique of anterior cervical reconstruction with pedicle screws
      and fibular strut grafting. METHODS: Seven patients with multilevel cervical
      myelopathy were treated with this new reconstruction technique after a 4-level
      corpectomy. We describe this new technique and review the patients' clinical
      history, results of radiographical imaging, and outcomes. Clinical outcomes were
      assessed preoperatively and at 3 months postoperatively. Postoperative
      radiographs were assessed 3 months and 6 months postoperatively. RESULTS: The
      mean operative time was 182 minutes and the mean blood loss was 271 mL. The
      average Japanese Orthopaedic Association score for cervical myelopathy improved
      from 11.5 points preoperatively to 14.5 points 3 months postoperatively. No
      patients experienced major complications, such as neurological deterioration,
      infection, or massive blood loss. There was no case of reconstruction failure,
      graft dislodgement, migration, or screw displacement. CONCLUSION: To our
      knowledge, this is the first description of an anterior cervical reconstruction
      approach, using pedicle screws and fibular strut grafting after a 4-level
      corpectomy. It is likely that this technique will result in better clinical
      outcomes with fewer complications in the treatment of patients with multilevel
      cervical myelopathy.

PMID- 22366967
TI  - Physical exercise affects cell proliferation in lumbar intervertebral disc
      regions in rats.
AB  - STUDY DESIGN: Descriptive experimental study. OBJECTIVE: The aim of this study
      was to investigate the effect of exercise on cell proliferation in different
      areas of the intervertebral disc (IVD) and recruitment of cells possibly active
      in regeneration of normal rat lumbar IVDs. SUMMARY OF BACKGROUND DATA: Little is
      known about the effects of physical exercise on lumbar IVD tissue. Recently, stem
      cell niches in the perichondrium area of the IVD were identified and cells in
      these niches have been suggested to be involved in the normal regeneration of the
      IVD. METHODS: Thirty Sprague-Dawley rats were exposed to 5-bromo-2-deoxyuridine
      (BrdU) diluted in the drinking water during 14 days. Fifteen rats ran on a
      treadmill daily for 50 min/d, 5 d/wk (exercise group), and 15 nonexercised rats
      served as controls. Immunohistochemical analyses (anti-BrdU antibody) were
      performed at 9, 14, 28, 56, and 105 days after the start of the exercise
      protocol. BrdU positive cells were counted in the stem cell niche area, the
      peripheral region of epiphyseal cartilage area, and the annulus fibrous outer and
      inner areas. Data were analyzed by 2-way analysis of variance (significance
      level; P < 0.05). RESULTS: The BrdU positive cell numbers in the stem cell niche
      and annulus fibrous outer regions were increased in discs from the exercising
      group on days 14 (P < 0.01) and 105 (P < 0.05) and at day 14 (P < 0.01) in the
      peripheral epiphyseal cartilage region compared with controls. CONCLUSION:
      Physical exercise was shown to have positive effects on cell proliferation in
      IVDs, with involvement of various disc regions, indicating a differential
      response by disc tissue to exercise depending on anatomical location and tissue
      characteristics.

PMID- 22366969
TI  - ISSLS prize winner: disc dynamic compression in rats produces long-lasting
      increases in inflammatory mediators in discs and induces long-lasting nerve
      injury and regeneration of the afferent fibers innervating discs: a
      pathomechanism for chronic discogenic low back pain.
AB  - STUDY DESIGN: Animal model of intravertebral disc (IVD) degeneration. OBJECTIVE:
      To examine production of inflammatory mediators in IVDs and neuropeptides in
      dorsal root ganglia (DRGs) in rat models of IVD compression and injury. SUMMARY
      OF BACKGROUND DATA: Sensory nerve fibers in IVDs and inflammatory mediator
      responses have been verified in animal models of IVD injury. However, the IVD
      injury in animals incompletely models degenerated human IVDs causing discogenic
      low back pain, because human IVDs are also subject to compression. METHODS:
      Experimental groups (controls, IVD injury, IVD compression, and their
      combination) of Sprague Dawley rats were prepared. Fluoro-Gold (FG; Fluorochrome,
      Denver, CO) was applied into coccygeal IVDs. Inflammatory mediators in IVDs,
      including nerve growth factor, tumor necrosis factor alpha, interleukin 1beta,
      and interleukin 6, were quantified using enzyme-linked immunosorbent assays. DRGs
      were immunostained for calcitonin gene-related peptide, activating transcription
      factor 3, and growth-associated phosphoprotein 43. RESULTS: The upregulation of
      inflammatory mediators was transient in the IVD injury group but delayed and long
      lasting in the IVD compression group. When the IVD injury and compression were
      combined, the upregulation of inflammatory mediators was long-lasting through 8
      weeks. The proportion of calcitonin gene-related peptide-immunoreactive neurons
      among Fluoro-Gold-labeled neurons remained significantly higher in the IVD
      injury, compression, and combination groups than in the controls. In contrast,
      increases in the proportions of activating transcription factor 3-immunoreactive
      or growth-associated phosphoprotein 43-immunoreactive neurons in the IVD injury
      group animals were transient but long-lasting in the compression and combination
      groups compared with controls. CONCLUSION: Disc injury in rats produces
      persistent increases in neuropeptides in DRGs but only transient increases in
      inflammatory mediators in IVDs. On the contrary, disc compression in rats
      produces a long-lasting increase in inflammatory mediators in IVDs and
      neuropeptides in DRGs. Moreover, disc compression induces persistent nerve injury
      and regeneration of the afferent fibers innervating IVDs.

PMID- 22366970
TI  - Upper instrumented vertebral fractures in long lumbar fusions: what are the
      associated risk factors?
AB  - STUDY DESIGN: A retrospective comparative study. OBJECTIVE: To investigate the
      risk factors associated with upper instrumented vertebral (UIV) fractures in
      adult lumbar deformity. SUMMARY OF BACKGROUND DATA: Long segment lumbar fusions
      may lead to junctional failures. The purpose of this study was to determine
      factors associated with junctional failures. METHODS: Twenty-seven consecutive
      patients from 2001 to 2008 with minimum 4 levels fused, lower instrumented
      vertebra (LIV) of L5 or S1, upper instrumented vertebra of T10 or distal, and no
      previous surgery proximal to the instrumentation were retrospectively reviewed.
      We describe the UIV angle, the sagittal angle of the upper instrumented vertebra
      with the horizontal. Patients were divided into 3 groups: group 1, 7 patients
      with UIV fractures; group 2, 6 patients with other proximal failures; and group
      3, 14 patients with no proximal complications. RESULTS: The mean number of levels
      fused was 5.7 (4-7), 5.2 (4-8), and 6.2 (4-8); mean age was 64.1, 61.8, and 64.1,
      and mean body mass index was 33.5, 30.0, and 31.6 for groups 1, 2, and 3,
      respectively (P > 0.05). Osteotomies were performed in 5 of 7 in group 1, 1 of 6
      in group 2, and 5 of 14 in group 3. Mean follow-up was 26.3 months. The average
      intraoperative UIV angle (UIV0) and immediate postoperative UIV angle (UIV1) were
      18.6 degrees /15.4 degrees  for group 1, 5.7 degrees /5.3 degrees  for group 2,
      and 10.3 degrees /7.1 degrees  for group 3 (P < 0.05). Surgical revision rates
      were higher in group 1 (71%) compared with groups 2 (50%) and 3 (43%). Eight of
      11 (73%) patients with upper instrumented vertebra of L1 or L2 had either UIV
      fracture or other proximal failure compared with 5 of 16 (31%) in patients with
      upper instrumented vertebra of T10, T11, or T12. CONCLUSION: Our series of long
      lumbar fusions had a high long-term complication and revision rate. A high UIV
      angle on intraoperative lateral radiograph was strongly associated with UIV
      fractures. UIVs of L1 or L2 had a higher rate of adjacent segment or UIV failure.

PMID- 22366957
TI  - Recent progress in histochemistry and cell biology.
AB  - Studies published in Histochemistry and Cell Biology in the year 2011 represent
      once more a manifest of established and newly sophisticated techniques being
      exploited to put tissue- and cell type-specific molecules into a functional
      context. The review is therefore the Histochemistry and Cell Biology's yearly
      intention to provide interested readers appropriate summaries of investigations
      touching the areas of tissue biology, developmental biology, the biology of the
      immune system, stem cell research, the biology of subcellular compartments, in
      order to put the message of such studies into natural scientific-/human- and also
      pathological-relevant correlations.

PMID- 22366971
TI  - Major complications and comparison between 3-column osteotomy techniques in 105
      consecutive spinal deformity procedures.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: To characterize the risk factors
      for the development of major complications in 3-column osteotomies and determine
      whether the presence of a major complication affects ultimate clinical outcomes.
      SUMMARY OF BACKGROUND DATA: Three-column spinal osteotomies, including pedicle
      subtraction osteotomy (PSO) and vertebral column resection (VCR), are common
      techniques to correct severe and/or rigid spinal deformities. METHODS: Two
      hundred forty consecutive PSO (n = 156) and VCR (n = 84) procedures in 237
      patients were performed at a single institution between 1995 and 2008. Of these,
      105 patients (87 PSOs, 18 VCRs) had complete preoperative and minimum 2-year
      postoperative clinical outcomes data available for analysis. Using established
      criteria, we reported complications as major or minor and further stratified
      complications as surgical versus medical and permanent versus transient. Risk
      factors for complications and their effect on Scoliosis Research Society (SRS)
      clinical outcomes at baseline and at 2 years or more were assessed. RESULTS:
      Major medical and surgical complications occurred at similar rates in both PSOs
      and VCRs (38%, 33 of 87 vs. 22%, 4 of 18; P = 0.28). Overall, 24.8% (26 of 105)
      experienced major surgical complications (3 permanent) and 15.2% (16 of 105)
      experienced major medical complications (4 permanent). Patients with PSO were
      older (53 vs. 29 yr; P < 0.001), had greater estimated blood loss (1867 vs. 1278
      mL; P = 0.02), and showed a trend toward fewer fused levels (10.1 vs. 12.2; P =
      0.06). Risk factors for major complications included preoperative sagittal
      imbalance of 40 mm or more (P = 0.01), age 60 years and older (P = 0.01), and the
      presence of 3 or more medical comorbidities (P = 0.04). Both groups improved
      significantly from baseline in SRS subscores; however, patients with PSO started
      off worse but improved more than VCRs in both the pain (+1.0 vs. +0.1; P < 0.001)
      and function (+0.6 vs. +0.2; P = 0.01) domains, with no differences in final
      satisfaction (4.1 vs. 4.3; P = 0.54). PSO and VCR patients with no complications
      had slightly higher satisfaction scores than patients with minor-only
      complications, major transient complications, and major permanent complications.
      There were no significant differences among the groups with respect to change in
      SRS subscores from baseline, and all complication groups improved significantly
      from baseline (P = 0.04). CONCLUSION: Major complications occurred in 35% of 3
      column osteotomies and at similar rates for both PSO (38%) and VCR (22%)
      procedures. The presence of a major complication did not affect the ultimate
      clinical outcomes at 2 years or more.

PMID- 22366972
TI  - Posterior extrapleural intervertebral space release combined with wedge osteotomy
      for the treatment of severe rigid scoliosis.
AB  - STUDY DESIGN: Retrospective clinical case series. OBJECTIVE: To report the
      technique and results of posterior extrapleural intervertebral space release
      (PEISR) combined with wedge osteotomy (WO) for the treatment of severe rigid
      scoliosis. SUMMARY OF BACKGROUND DATA: Conventional surgical correction
      techniques for severe rigid scoliosis include anterior release combined with
      posterior instrumentation and fusion and vertebral column resection. METHODS:
      Between 2004 and 2009, 18 patients underwent PEISR and WO at a single
      institution. The indications were scoliosis with coronal Cobb's angle greater
      than 90 degrees  and curve flexibility less than 25%. The median age at surgery
      was 18.1 years (range, 13-26 yr). Nine patients had a preoperative forced vital
      capacity that was less than 40% of predicted. All patients had a minimum 2-year
      radiographical and clinical follow-up (range, 2.0-5.7 yr). RESULTS: A mean of 4.2
      discs were excised per patient (range, 2-6 discs) along with a mean of 1.2
      vertebrae removed in the osteotomy. Mean number of vertebrae fused was 13.8
      (range, 10-16 vertebrae). Mean operating time was 8.8 hours (range, 6.2-12.6 hr),
      with a mean blood loss of 3990 mL (range, 2600-6100 mL). The mean preoperative
      Cobb angle of 108.5 degrees  (range, 92 degrees -136 degrees ) was corrected to
      30 degrees  at the most recent follow-up (72.4% correction rate). Preoperative
      thoracic kyphosis of 52 degrees  (range, 5 degrees -115 degrees ) was corrected
      to 26 degrees  (range, 17 degrees -52 degrees ). The mean preoperative coronal
      imbalance of 3.5 cm was corrected to 0.6 cm (83.8% correction) and the sagittal
      imbalance of 2.8 cm was corrected to 0.3 cm (90.3% correction). There were no
      neurological complications. There were no instances of infection or muscle
      necrosis. Hemopneumothorax occurred in 2 patients. CONCLUSION: PEISR, combined
      with WO, through a single posterior approach is a technically challenging but
      safe and effective procedure for severe rigid scoliosis. This posterior-only
      approach allows for dramatic radiographical correction that surpasses that
      reported for posterior VCR.

PMID- 22366973
TI  - Evaluation of echogenic emboli during total knee arthroplasty using transthoracic
      echocardiography.
AB  - PURPOSE: Tranesophageal echocardiography or direct sampling of arterial and/or
      right atrial blood with histological evaluation are invasive techniques used to
      evaluate embolic material entering the heart during total knee arthroplasty
      (TKA). The aim of this study was to develop a non-invasive method of detecting
      and quantifying the embolic matter using transthoracic echocardiography and to
      apply this method to compare the incidence and severity of embolism between
      computer-navigated (N) and conventional (C) TKA done under tourniquet. METHODS:
      Twenty-eight patients (15 N-TKA and 13 C-TKA) were enrolled. Transthoracic
      echocardiography was performed in all standard views prior to surgery and
      continuously after the tourniquet release for monitoring the echodense
      particulates appearing in the right atrium. To estimate the severity of echogenic
      embolization, maximum absolute increase in luminosity after tourniquet release
      (peak embolic load) and area under the curve (AUC; total embolic load) were both
      calculated. RESULTS: Twenty-four (85%) had significant particulate matter in
      right atrium (median time from release of thigh tourniquet to peak embolization
      in right atrium: 18.0 s). Peak embolic load was lower in N-TKA than C-TKA [17.0
      versus 35.0 arbitrary luminosity units, p = 0.03]. Total embolic load, by area
      under the curve, was lower in the N-TKA group. CONCLUSIONS: Perioperative
      particulate embolization during TKA can be quantified non-invasively with the use
      of transthoracic echocardiography and off-line image analysis. N-TKA, by virtue
      of avoiding intramedullary guides, causes lesser total embolic load and hence can
      lead to decreased the severity and incidence of this potentially fatal
      phenomenon. LEVEL OF EVIDENCE: II.

PMID- 22366974
TI  - No difference between tibia-first and femur-first techniques in TKA using
      computer-assisted surgery.
AB  - PURPOSE: The measured resection technique and the gap-balancing technique are two
      philosophies used in total knee surgery. It is still unknown whether one or the
      other technique provides superior results when computer-assisted surgery is
      performed. We hypothesized that the gap-balancing technique improves joint
      stability because the technique relies primarily on the soft tissue. METHODS: A
      prospective controlled study was performed in 116 patients using the tibia-first
      or femur-first technique. The Columbus(TM) total knee system and the
      Orthopilot((r)) (Aesculap((r)) AG, Tuttlingen, Germany) navigation system were
      used in all cases. Sixty-three patients were allocated to the femur-first
      technique (group F) and 53 patients to the tibial first technique (group T). The
      mean follow-up time was 11.4 +/- 1.1 months. The KSS, KOOS and SF-36 were taken
      prior to surgery and at the time of follow-up for clinical assessment. Long-leg
      weight-bearing radiographs were performed to assess ligament alignment.
      Radiographs in varus and valgus stress were performed using the Telos((r))
      Instrument (Telos((r)) GmbH, Greisheim, Germany) under a force of 15 N at the
      time of follow-up for the assessment of medial-lateral stability. The
      nonparametric t test (Mann-Whitney U-test) was used in order to compare the
      ligament stability and the scores between group F and group T. RESULTS: The
      lateral joint space opening for groups F and T was 3.4 degrees  +/- 1.4 degrees 
      and 3.9 degrees  +/- 1.7 degrees , respectively (n.s.), and the medial joint
      space opening for groups F and T was 4 degrees  +/- 1.4 degrees  and 4.1 degrees 
      +/- 1.7 degrees , respectively (n.s.). The femorotibial mechanical axis for
      groups F and T revealed 1.4 degrees  +/- 1.2 degrees  and 0.7 degrees  +/- 2.0
      degrees  of varus, respectively (p = 0.138). The clinical assessment showed
      significant improvement according to KSS, KOOS and SF-36 in all subscales.
      Neither of the sores showed significant differences between the two groups.
      CONCLUSION: The surgeon should use his/her preferred surgical technique providing
      the implantation is performed with computer assistance. It remains unclear
      whether the same findings will occur after conventional surgery. LEVEL OF
      EVIDENCE: II.

PMID- 22366975
TI  - Patient selection of anatomical double bundle or traditional single bundle ACL
      reconstruction.
AB  - PURPOSE: This study was designed as a questionnaire survey to reveal the
      preference in technique of patients faced with anterior cruciate ligament (ACL)
      reconstruction. METHODS: One hundred and ten subjects (35 patients and 75 medical
      students) were included in this study. A questionnaire survey was conducted, and
      the following questions were asked: (1) How old are you? (2) Prior to this
      survey, did you know what the ACL was? (3) Prior to this survey, did you have any
      knowledge about ACL reconstruction technique? (4) Prior to this survey, did you
      know the difference between anatomical double bundle (DB) technique and
      traditional single bundle (SB) technique? (5) If you had to have an ACL
      reconstruction, which technique would you prefer? In the same questionnaire,
      between questions (3) and (4), a description of SB and DB was provided. RESULTS:
      Sixty-nine percent of patients and 100% of medical students knew what the ACL
      was. Forty-three percent of patients and 85% of medical students had previous
      knowledge about ACL reconstruction. None of the patients and only 29% of the
      medical students had prior knowledge about the difference between DB and SB. Six
      percent of patients selected SB, and 40% selected DB. Nine percent of medical
      students selected SB, and 67% selected DB. CONCLUSION: In this study, 46% of
      patients and 76% of medical students selected one of the operation techniques.
      The trend in selection of the operation technique was significantly influenced by
      the subjects' prior medical knowledge. It might be possible to apply the
      principle of "informed patient choice" to the selection of DB or SB for ACL
      reconstruction. LEVEL OF EVIDENCE: Decision analysis, Level III.

PMID- 22366976
TI  - Criteria for the evaluation of a cloud-based hospital information system
      outsourcing provider.
AB  - As cloud computing technology has proliferated rapidly worldwide, there has been
      a trend toward adopting cloud-based hospital information systems (CHISs). This
      study examines the critical criteria for selecting the CHISs outsourcing
      provider. The fuzzy Delphi method (FDM) is used to evaluate the primary indicator
      collected from 188 useable responses at a working hospital in Taiwan. Moreover,
      the fuzzy analytic hierarchy process (FAHP) is employed to calculate the weights
      of these criteria and establish a fuzzy multi-criteria model of CHISs outsourcing
      provider selection from 42 experts. The results indicate that the five most
      critical criteria related to CHISs outsourcing provider selection are (1) system
      function, (2) service quality, (3) integration, (4) professionalism, and (5)
      economics. This study may contribute to understanding how cloud-based hospital
      systems can reinforce content design and offer a way to compete in the field by
      developing more appropriate systems.

PMID- 22366977
TI  - Sharing personal health information via service-oriented computing: a case of
      long-term care.
AB  - Sharing personal health information among healthcare providers is a crucial
      business process not only for saving limited healthcare resources but also for
      increasing patient's healthcare quality. Building an effective personal health
      information sharing process from established healthcare systems is a challenge in
      terms of coordination different business operations among healthcare providers
      and restructuring technical details existed in different healthcare information
      systems. This study responds this challenge with a service-oriented approach and
      develops a business software application to describe how the challenge can be
      alleviated from both managerial and technical perspectives. The software
      application in this study depicts personal health information sharing process
      among different providers in a long-term care setting. The information sharing
      scenario is based on an industrial initiative, such as Integrating the Healthcare
      Enterprise (IHE) from healthcare domain and the technologies for implementing the
      scenario are Web Service technologies from Service-oriented computing paradigm.
      The implementation in this study can inform healthcare researchers and
      practitioners applying technologies from service-oriented computing to design and
      develop healthcare collaborative systems to meet the increasing need for personal
      health information sharing.

PMID- 22366978
TI  - The ecology of emerging infectious diseases in migratory birds: an assessment of
      the role of climate change and priorities for future research.
AB  - Pathogens that are maintained by wild birds occasionally jump to human hosts,
      causing considerable loss of life and disruption to global commerce. Preliminary
      evidence suggests that climate change and human movements and commerce may have
      played a role in recent range expansions of avian pathogens. Since the magnitude
      of climate change in the coming decades is predicted to exceed climatic changes
      in the recent past, there is an urgent need to determine the extent to which
      climate change may drive the spread of disease by avian migrants. In this review,
      we recommend actions intended to mitigate the impact of emergent pathogens of
      migratory birds on biodiversity and public health. Increased surveillance that
      builds upon existing bird banding networks is required to conclusively establish
      a link between climate and avian pathogens and to prevent pathogens with
      migratory bird reservoirs from spilling over to humans.

PMID- 22366979
TI  - A magnetic iron(III) switch with controlled and adjustable thermal response for
      solution processing.
AB  - Spin crossover requires cooperative behavior of the metal centers in order to
      become useful for devices. While cooperativity is barely predictable in solids,
      we show here that solution processing and the covalent introduction of molecular
      recognition sites allows the spin crossover of iron(III) sal(2)trien complexes to
      be rationally tuned. A simple correlation between the number of molecular
      recognition sites and the spin crossover temperature enabled the fabrication of
      materials that are magnetically bistable at room temperature. The predictable
      behavior relies on combining function (spin switching) and structure
      (supramolecular assembly) through covalent interactions in a single molecular
      building block.

PMID- 22366980
TI  - Validation of a questionnaire to detect kinesiophobia (fear of movement) in
      patients with coronary artery disease.
AB  - OBJECTIVE: To investigate the validity and reliability of the Tampa Scale for
      Kinesiophobia Heart (TSK-SV Heart), a brief questionnaire to detect kinesiophobia
      (fear of movement) in patients with coronary artery disease. DESIGN:
      Methodological research (cross-sectional study). SUBJECTS: A total of 332
      patients, mean age 65 years (standard deviation 9.1) diagnosed with coronary
      artery disease at a university hospital were included in the study. METHODS: The
      psychometric properties of the TSK-SV Heart were tested. The tests of validity
      comprised face, content, and construct validity. The reliability tests included
      composite reliability, internal consistency and stability over time. RESULTS: In
      terms of reliability, the TSK-SV Heart was found to be stable over time (intra
      class correlation coefficient 0.83) and internally consistent (Cronbach's alpha
      0.78). Confirmatory factor analysis provided acceptable fit for a hypothesized 4
      factor model with inclusion of a method factor. CONCLUSION: These results provide
      support for the reliability of the TSK-SV Heart. The questionnaire appears to be
      valid for use in patients with coronary artery disease. However, some items
      require further investigation due to low influence on some sub-dimensions of the
      test. The sub-dimensions of kinesiophobia require future research concerning
      their implications for the target group.

PMID- 22366981
TI  - Heat production, nerve function, and morphology following nerve close dissection
      with surgical instruments.
AB  - BACKGROUND: The aim of the present study was to compare an ultrasonically
      activated instrument (US), monopolar electrosurgery, and bipolar electrosurgery
      (ES) with respect to heat production, nerve function, and nerve morphology
      following in vivo application. MATERIALS AND METHODS: The biceps femoris muscle
      of anesthetized rats was cut in a standardized manner longitudinally 1 mm
      adjacent to the sciatic nerve using US shears, a monopolar ES knife, or a bipolar
      ES scissors. Activation time and temperature were recorded continuously within 1
      4 mm of the activation site ipsilateral and contralateral to the nerve with two
      thermoelectric microsensors. Temperature rise and time delay of reaching the
      temperature maximum, as an expression of heat spread within tissue, maximum
      temperature, and thermal dose (equivalent time of exposure at 43 degrees C) were
      measured and calculated. A total of 49 functional experiments were conducted. The
      electromyographic (EMG) potential was recorded distally. Nerve dysfunction was
      defined as more than 10% loss of the evoked EMG amplitude. Forty-eight nerves
      were coded and submitted to blind histopathological examination, and
      morphological damage was graded on a 4-grade scale. RESULTS: The maximum
      temperature elevation and the thermal dose were significantly higher for the
      bipolar ES compared with the US instrument (p = 0.024, p = 0.049), and with much
      less variation of results for the US instrument. The monopolar ES maximum
      temperature and thermal dose were lower, but a very large variation occurred,
      probably as a result of more random electrical spread to the ground electrode and
      muscle motion artifacts. Functional loss was least common in the US group-without
      being significant-compared to bipolar and monopolar ES. Moderate and severe
      morphological damage was significantly less common in the US group than in the
      monopolar ES group (p = 0.041). We found no statistically significant correlation
      between the highest temperatures and the degree of morphological damage or
      functional loss. CONCLUSIONS: The temperature elevation depends strongly on the
      distance to the activated instrument. The bipolar ES scissors generates a higher
      maximum temperature and thermal dose with a greater variation in than the US.
      Functional loss and severe morphological damage were uncommon in all groups.

PMID- 22366982
TI  - Completion thyroidectomy: effect of timing on clinical complications and
      oncologic outcome in patients with differentiated thyroid cancer.
AB  - BACKGROUND: Despite improved preoperative diagnostics, incidental postoperative
      detection of differentiated thyroid cancer in the final histology is still
      common. In most of these cases, completion thyroidectomy is recommended by
      national and international guidelines, although secondary surgery is associated
      with an increased operative risk. The optimal timing of completion thyroidectomy
      is still controversial. METHODS: Between January 1993 and December 2009, a total
      of 128 patients underwent completion thyroidectomy for differentiated thyroid
      carcinoma: papillary (n = 87) and follicular (n = 41). These patients were
      divided into five groups according to the time of the completion thyroidectomy
      after primary surgery (groups A, 1-3 days; B, 4-7 days; C, 1-7 weeks; D, 7-12
      weeks; E, >3 months). Clinical complications and oncologic outcomes were
      analyzed. The mean follow-up was 82.5 +/- 17 months. RESULTS: The overall rates
      of transient and persistent postoperative hypocalcemia were 7.0 and 3.1%,
      respectively. The rates of persistent hypocalcemia were significantly increased
      in groups B, C, and D in comparison to those in groups A and E (p < 0.003). The
      hypocalcemia rates were 7.1, 4.5, and 3.8% versus 0%, respectively. Transient or
      persistent vocal cord paresis was observed in eight (6.2%) and four patients
      (3.1%), respectively. The incidence of persistent vocal cord paresis (VCP) was
      significantly higher in groups B, C, and D than in groups A and E (p < 0.003).
      The VCP rates were 7.1, 4.5, and 3.8% versus 0%, respectively. There was no
      significant difference regarding survival or recurrence among the five groups.
      CONCLUSIONS: Considering perioperative morbidity and oncologic outcomes,
      completion thyroidectomy should be performed either within 3 days or beyond 3
      months after primary surgery.

PMID- 22366983
TI  - The effect of the neutrophil elastase inhibitor sivelestat on early injury after
      liver resection.
AB  - BACKGROUND: The effects of sivelestat on endotoxin-induced lung injury,
      postperfusion lung injury, and ischemia-reperfusion are known, yet the benefits
      of sivelestat during liver surgery have yet to be elucidated. The aim of the
      present study was to assess the effects of sivelestat, with a focus on
      postoperative chemical data, in hepatectomized patients. PATIENTS AND METHODS: A
      prospective clinical study was conducted in 50 patients undergoing hepatic
      resection. Patients were randomly assigned to receive Elaspol, sivelestat (ELP
      group, n = 25) or placebo (control group, n = 25). Perioperative blood chemistry
      values in both groups, including high-mobility group box 1 (HMGB1) and
      interleukin (IL)-6, were monitored. RESULTS: The HMGB1 levels increased
      immediately after the operation (from the intraoperative period to the second
      postoperative day [POD]) in the control group. Compared to the control group, the
      levels of HMGB1 in the ELP group were significantly suppressed by the
      perioperative administration of sivelestat. At POD 1, the levels of IL-6 in the
      ELP group decreased more rapidly than those before the operation compared to the
      control group. CONCLUSIONS: A human clinical study demonstrated the effect of
      polymorphonuclear leukocyte elastase inhibitor on the earliest markers of liver
      injury. The present study showed that patients who received sivelestat had
      reduced release of HMGB1, and that IL-6 levels decreased more rapidly in patients
      treated with sivelestat than in those who received the placebo. The most
      appropriate dose, timing, and duration of sivelestat in humans remain unclear;
      however, it may have therapeutic potential for various liver injuries.

PMID- 22366984
TI  - Cancer stem cell marker Bmi-1 expression is associated with basal-like phenotype
      and poor survival in breast cancer.
AB  - BACKGROUND: The purpose of present study was to examine the expression of cancer
      stem cell marker Bmi-1 in breast cancer tissue and to evaluate the clinical
      implication of Bmi-1 expression for these patients. METHODS: A total of 171
      breast cancer patients who received surgical treatment in our hospital were
      enrolled in this study. Bmi-1 expression in breast cancer tissue was assayed by
      immunohistochemistry. Statistical analyses were applied to test the relationship
      between expression of Bmi-1 and clinicopathologic features and patient survival.
      The relationship between Bmi-1 and the basal-like phenotype of breast cancer also
      was analyzed in this study. RESULTS: Positive Bmi-1 expression was detected in 89
      of 171 (52%) invasive breast cancers patients. The Bmi-1 status was significantly
      correlated to histological grade III (p = 0.001) and basal-like phenotype (p <
      0.001). The 5 year overall survival of the patients with Bmi-1-positive and 
      negative cancers were 78 and 91.9%, respectively (p = 0.03). Histological grade
      (p = 0.046) and Bmi-1 status (p = 0.012) were detected as the independent
      prognostic factors in the Cox regression test. CONCLUSIONS: Bmi-1 status is an
      independent prognostic factor, which also is associated with tumor histological
      grade and basal-like phenotype. The high proportions of positive Bmi-1 expression
      in basal-like breast cancer may be related to the high aggressiveness behavior of
      this subtype of breast cancer.

PMID- 22366986
TI  - Assessment of a prevention program for work-related stress among urban police
      officers.
AB  - OBJECTIVE: To determine the efficacy of a primary prevention program designed to
      improve psychobiological responses to stress among urban police officers.
      METHODS: A random sample of 37 police cadets received complementary training in
      psychological and technical techniques to reduce anxiety and enhance performance
      when facing a series of police critical incidents. Training was done by Special
      Forces officers, trained by the authors in imaging. A random sample of 38 cadets,
      receiving training as usual, was followed in parallel. Assessment of somatic and
      psychological health, and stress biomarkers, was done at baseline, immediately
      following training, and after 18 months as regular police officers. Comparison
      was done using two-way repeated analysis of variance (ANOVA) and logistic
      regression. RESULTS: The intervention group improved their general health and
      problem-based coping as compared to the control group. They also demonstrated
      lower levels of stomach problems, sleep difficulties, and exhaustion. Training
      was associated with an OR of 4.1 (95% CI, 1.3-13.7; p < 0.05) for improved GHQ
      scores during the study as compared to no changes or worsening score.
      CONCLUSIONS: This first primary prevention study of high-risk professions
      demonstrates the validity and functional utility of the intervention. Beneficial
      effects lasted at least during the first 2 years on the police force. It is
      suggested that preventive imagery training in first responders might contribute
      to enhanced resiliency.

PMID- 22366987
TI  - Health effects and acceptance of a physical activity program for older long-term
      unemployed workers.
AB  - PURPOSE: Long-term unemployment has negative effects on both mental and physical
      health. In combination with an inactive lifestyle, it often leads to functional
      or constitutional limitations that make reemployment in the labor market
      difficult especially for older adults. The presented pilot study examined a 3
      month-long interventional program for improving health of older, long-term
      unemployed persons with regard to its effectiveness and acceptance by the target
      group. METHODS: The low-threshold intervention was offered by a job training
      center that supports reemployment and was divided into lectures for enhancing the
      individual health competence and a supervised physical training part in a fitness
      center. One hundred and nineteen long-term unemployed workers (53.7 +/- 3 years)
      took part in a prospective investigation with 3 data collection points: before
      intervention (T1), after intervention (T2, n = 94), and 6 month after
      intervention (T3, n = 59). The spectrum of methods included the assessment of
      nutritional status, cardiovascular risk factors, physical fitness, chronic
      backache, and depression. RESULTS: As a result of the intervention, the physical
      fitness improved significantly (maximal oxygen uptake: p < 0.002). Cardiovascular
      risk factors like systolic and diastolic blood pressure (p < 0.016; p < 0.001)
      and percentage body fat (p < 0.017) decreased significantly. There were also
      remarkable effects in the reduction in depression (p < 0.028). Chronic backache
      was lowered in more than 50% of the cases. CONCLUSION: The health promotion
      program reached people who have a desire to improve both physical and mental
      health. To assume responsibility for their own health may be a first step in
      regaining self-confidence and lowering the work placement barriers.

PMID- 22366988
TI  - Association between ambient ozone and health outcomes in Prague.
AB  - PURPOSE: Though numerous studies investigating ambient ozone (O(3)) effects on
      human health were published, such a study for Central Europe is still lacking. We
      have investigated the association between ozone (O(3)) levels and hospital
      admissions and mortality due to cardiovascular and respiratory diseases for
      Prague inhabitants for summer months (April-September) over the 5-year period
      2002-2006. Our hypothesis was that ambient O(3) levels in Prague resulted in
      adverse health outcomes and were associated with increased mortality and hospital
      admissions. METHODS: The effect of O(3) on mortality and hospital admissions was
      investigated using the negative binomial regression after controlling for the
      influence of meteorological factors (air temperature and relative humidity) and
      calendar effects (seasonal patterns, long-term trends and day of week). RESULTS:
      We found a statistically significant association between O(3) levels and daily
      mortality from respiratory diseases. Relative risk of 1.080 (95% CI: 1.031-1.132)
      was observed for mortality from respiratory diseases per 10 MUg m(-3) increase in
      1-day lagged daily mean O(3) concentration. No statistically significant
      association was detected between O(3) concentrations and daily mortality from all
      causes, daily mortality from cardiovascular diseases and hospital admissions for
      respiratory and cardiovascular diseases. The O(3) effects differed in men and
      women, nevertheless, the results were ambiguous with respect to used lag and O(3)
      metrics. No significant confounding effects of PM(10) on the investigated
      association were observed. CONCLUSIONS: O(3) exposure in Prague, though lower as
      compared to many other cities in Europe, is high enough to cause adverse health
      effects.

PMID- 22366989
TI  - Exploration of patient-centered success criteria and clinically measured
      improvement during falls rehabilitation.
AB  - BACKGROUND AND PURPOSE: One method for defining successful rehabilitation
      outcomes is to use a threshold of performance on a clinical measure. Patients
      also have their own criteria for success. The aim of this study was to examine
      the association between clinical measures and patient criteria for determining
      successful intervention. METHODS: Twenty-two participants participated in a 12
      week intervention program for balance disorders. Participants were tested using
      the Berg balance scale (BBS) and dynamic gait index (DGI) at the first and final
      visits. They also used the patient's perspective outcomes questionnaire (PPOQ) at
      the first visit to rate impairments in the core domains from the international
      classification of Function. Participants rated their usual levels of impairment
      across domains, their desired levels of impairment after intervention (success
      criteria), and how important it was to change in each domain. At the final visit,
      all participants used the PPOQ to rate their current impairment across domains
      and completed a 15-point global rating of change (GRC). The intervention was
      defined as a success if the participant rated himself or herself as "a great
      deal" or "a very great deal" better using the GRC. Changes in the BBS and the DGI
      were dichotomized on the basis of whether the change exceeded the minimal
      detectable change (MDC) of the instrument. Participants' ratings of impairment at
      12 weeks were compared with their success criteria and dichotomized on the basis
      of whether the success criteria had been met. The Freidman test was used to test
      differences across domains at baseline with Wilcoxon tests for follow-up.
      Wilcoxon tests were also used to examine the importance of change across domains.
      Chi-square tests were used to explore the association among the GRC, performance
      on clinical tests, and whether success criteria were met. RESULTS: Significant
      changes were noted for the group for both BBS (P < .001) and DGI (P = .006). Only
      40% of participants exceeded or met their desired or expected change in
      impairment for mobility. No significant associations were noted between exceeding
      MDC on the BBS or DGI and any of the domains on the PPOQ (all Ps = .263).
      Bivariate associations were noted between baseline measures of psychological
      factors and many of the participant ratings of impairment. Fifty-five percent of
      participants indicated that they were a great deal better or a very great deal
      better. Significant association was identified between success and exceeding MDC
      on the BBS (chi = 5.84, P = .016) but not the DGI. When considering participants'
      desired change in impairment, only meeting desired changes in mental function was
      associated with considering the intervention a success (chi = 4.55, P = .033).
      DISCUSSION: Treatment success from the perspective of this group of older adults
      was related to improvement on a clinic-based performance measure and not the
      participants' intrinsic success criteria assessed at the beginning of the
      intervention. CONCLUSION: Making measurable change in gait and balance translates
      into perceived success for the patient with a balance disorder.

PMID- 22366990
TI  - Transforming growth factor-beta1-gene polymorphism in the development of kidney
      disease after liver transplantation.
AB  - BACKGROUND: The development of kidney dysfunction is one of the most important
      after liver transplantation (LT). Genetic variants of pathogenetically relevant
      cytokines may influence the development and course of the disease. The aim of our
      study was to evaluate the role of transforming growth factor-beta1 (TGF-beta1)
      polymorphism in this context. METHODS: Four hundred eighty-six liver graft
      recipients were genotyped for TGF-beta1 codon 25 (guanine -> cytosine, G -> C) by
      polymerase chain reaction. Renal function before and after LT was characterized
      by estimation of glomerular filtration rate (GFR) using four-parameter
      modification of diet in renal disease formula on defined dates. GFR was compared
      among TGF-beta1-genotype groups of the entire cohort within the median
      observation period of 7 years. For the assessment of renal function recovery
      after LT, patients were divided into three groups by GFR difference (DeltaGFR =
      +/- 10 mL/min). RESULTS: Mean pretransplant GFR differed significantly among TGF
      beta1-genotype groups (GG: 85.0 mL/min vs. GC/CC: 75.3 mL/min; P=0.016). The
      significance disappeared in the follow-up period. Although GG genotype
      demonstrated higher mean GFR levels, patients with GC/CC genotype tended to
      improve kidney function compared with GG genotype (P=0.013). Interestingly, lower
      mean GFR rates were observed among female compared with male recipients before
      (P=0.002), separately at all dates and cumulatively after LT (P<0.001).
      CONCLUSIONS: Genetic variants of one of the most important cytokine TGF-beta1 at
      codon 25 may have an impact on kidney function, suggesting an unfavorable effect
      of C allele in pretransplant setting and serve as marker for the recovery of
      renal function after LT. The identification of further confounders seems to be
      promising.

PMID- 22366991
TI  - Genome-wide identification of OTP gene as a novel methylation marker of breast
      cancer.
AB  - Aberrant DNA methylation occurs early and frequently in tumorigenesis.
      Identification of DNA methylation biomarkers is a field that provides potential
      for improving the clinical process of breast cancer diagnosis. We utilized a
      genome-wide technique, methylated DNA isolation assay (MeDIA), in combination
      with high-resolution CpG microarray analysis to identify hypermethylated genes in
      breast cancer. Among differentially methylated genes between tumor and adjacent
      normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected
      through a step-wise filtering process and examined for methylation status in
      normal tissues, primary tumor, and paired adjacent normal-appearing tissues from
      39 breast cancer patients. Based on the calculated cut-off values, all genes
      showed significantly higher frequencies of aberrant hypermethylation in primary
      tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, p<0.05) while frequencies
      were intermediate in paired adjacent normal tissues and absent in normal tissues.
      On further analysis, the methylation level in primary tumors was not
      significantly correlated with clinicopathological features. Interestingly, DNA
      methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm
      away from primary tumors, suggesting that OTP methylation may qualify as a
      biomarker for the early detection of breast cancer. In conclusion, we
      successfully identified a novel gene OTP frequently methylated in breast cancer
      by genome-wide screening. Our results suggest that the OTP gene may play a
      crucial role in breast carcinogenesis, although further clinical validation will
      be needed to evaluate the potential application of OTP in the early detection of
      breast cancer.

PMID- 22366992
TI  - Progestin therapy for endometrial cancer: the potential of fourth-generation
      progestin (review).
AB  - Progestin preparations are made of synthetic progesterone and have often been
      used for hormone therapy in gynecological patients with endometriosis or
      endometrial cancer. Hormone therapy using progestin is considered to be one of
      the effective means of treatment particularly when dealing with endometrial
      cancer (an estrogen-dependent tumor). Numerous reports have been published
      concerning its efficacy in advanced or recurrent cases of atypical endometrial
      hyperplasia or endometrial cancer. Dienogest has been developed as a fourth
      generation progestin for hormone therapy for endometriosis that can be used with
      high safety for long periods of time. In Japan, dienogest has been recommended as
      a first-line drug for endometriosis-associated pain. However, its antitumor
      activity has also been attracting close attention following a report that this
      drug suppressed the proliferation in vitro of endometrial cancer-derived cell
      lines which failed to respond to other progestins such as medroxyprogesterine
      acetate (MPA). The mechanism for antitumor activity of dienogest is considered to
      differ from the mechanism for antitumor activity of conventional progestin
      preparations used for treatment of endometrial cancer. This drug is expected to
      be clinically applicable as a new drug for the treatment of endometrial cancer.

PMID- 22366993
TI  - New respiratory viral infections.
AB  - PURPOSE OF REVIEW: The first era in the discoveries of respiratory viruses
      occured between 1933 and 1965 when influenza virus, enteroviruses, adenovirus,
      respiratory syncytial virus, rhinovirus, parainfluenza virus and coronavirus
      (CoV) were found by virus culture. In the 1990s, the development of high
      throughput viral detection and diagnostics instruments increased diagnostic
      sensitivity and enabled the search for new viruses. This article briefly reviews
      the clinical significance of newly discovered respiratory viruses. RECENT
      FINDINGS: In 2001, the second era in the discoveries of respiratory viruses
      began, and several new respiratory viruses and their subgroups have been found:
      human metapneumovirus, CoVs NL63 and HKU1, human bocavirus and human rhinovirus C
      and D groups. SUMMARY: Currently, a viral cause of pediatric respiratory illness
      is identifiable in up to 95% of cases, but the detection rates decrease steadily
      by age, to 30-40% in the elderly. The new viruses cause respiratory illnesses
      such as common cold, bronchitis, bronchiolitis, exacerbations of asthma and
      chronic obstructive pulmonary disease and pneumonia. Rarely, acute respiratory
      failure may occur. The clinical role of other new viruses, KI and WU
      polyomaviruses and the torque teno virus, as respiratory pathogens is not clear.

PMID- 22366994
TI  - Diagnostics for community-acquired and atypical pneumonia.
AB  - PURPOSE OF REVIEW: After decades of neglect, the importance of establishing an
      aetiological diagnosis for community-acquired and atypical pneumonias has
      increased dramatically in recent years--driven by the movement towards more
      rational use of antibiotics, the further spread of antimicrobial resistance, and
      advances in point-of-care assays that circumvent the diagnostic delays that
      result from the centralization of laboratories. RECENT FINDINGS: There have been
      very few developments in patient sampling, or the direct visualization, culture,
      and serological detection of respiratory pathogens. There has, however, been
      significant interest in the development of improved and more clinically useful
      assays for the detection of pathogen nucleic acids and proteins, and also in the
      potential utility of the assessment of host response for tailoring therapy.
      SUMMARY: The majority of patients have yet to benefit from any advances. However,
      nucleic acid, newer protein, and possibly host-response assays have significant
      potential to influence patient care in the near future.

PMID- 22366995
TI  - Ventilator-associated pneumonia caused by ESKAPE organisms:  cause, clinical
      features, and management.
AB  - PURPOSE OF REVIEW: Despite important geographical variations, Enterococcus
      faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,
      Pseudomonas aeruginosa and Enterobacter species (ESKAPE) pathogens constitute
      more than 80% of ventilator-associated pneumonia (VAP) episodes. Their clinical
      importance relies on their virulence and ability in developing mechanisms to
      decrease susceptibility to antimicrobials, increasing inappropriate therapy and
      affecting negatively on ICU patients' outcome. This review updates information on
      VAP due to ESKAPE pathogens. RECENT FINDINGS: Although methicillin-resistant
      Staphylococcus aureus VAP may be clinically similar to that caused by susceptible
      strains, it is associated with poorer outcomes despite adequate treatment. Local
      colonization determines treatment options. The contribution of tracheobronchitis
      is an important issue. Minimum inhibitory concentration should be considered for
      nonfermentative Gram-negative bacteria VAP to prescribe extended infusion beta
      lactam treatment due to an increase of resistant strains. Strategies promoting
      antimicrobial diversity may protect against emergence and spread of resistance by
      ESKAPE pathogens. SUMMARY: VAP due to ESKAPE pathogens represents a global
      challenge that can be prevented using stewardship programmes promoting diversity.

PMID- 22366996
TI  - Developments in novel breath tests for bacterial and fungal pulmonary infection.
AB  - PURPOSE OF REVIEW: Breath testing has developed over the last 20 years. New
      techniques that can identify fingerprints for specific diseases and specific
      markers of respiratory pathogens have been applied to breath analysis. This
      review discusses the recent advances in breath analysis for the diagnosis of
      bacterial and fungal lower respiratory tract infections. RECENT FINDINGS: The
      current techniques continue to develop rapidly, but preconcentration techniques
      are needed to analyse many target volatile organic compounds for most systems.
      Breath testing with an electronic nose is promising for the diagnosis of
      tuberculosis (TB), and specific volatiles identifiable by gas chromatography with
      mass spectrometry have been identified in breath for Mycobacterium tuberculosis,
      Pseudomonas aeruginosa and Aspergillus fumigatus, but are found at very low
      concentrations in breath. Contamination from the environment is an ongoing
      confounding influence. Exhaled breath condensate (EBC) is disappointing as a
      diagnostic sample. SUMMARY: Careful attention needs to be paid to the sensitivity
      and specificity of a technique and confounding from the environment. The role of
      technologies such as selected ion flow tube-mass spectrometry is emerging. The
      electronic nose requires further validation for TB. The identification of
      specific microbial biomarkers aids the quest for improved accuracy. EBC is
      currently of limited value.

PMID- 22366997
TI  - Isoproterenol infusion increases level of consciousness during catheter ablation
      of atrial fibrillation.
AB  - INTRODUCTION: The objective of this study was to determine the effects of
      isoproterenol infusion on level of consciousness during ablation using total
      intravenous anesthesia. METHODS AND RESULTS: Seven patients undergoing total
      intravenous anesthesia for atrial fibrillation ablation were monitored for level
      of consciousness using bispectral EEG levels (BIS). Isoproterenol infusion was
      performed after the ablation during anesthesia. BIS levels prior to, during, and
      post-isoproterenol infusion were recorded and correlated to isoproterenol
      infusion doses. In all patients, BIS levels significantly increased during
      isoproterenol infusion (median BIS prior to infusion, 46; during infusion, 64 (p
      < 0.02)). With a subsequent increase in anesthetic medication, BIS levels could
      again be reduced. CONCLUSION: Isoproterenol infusion alters consciousness level
      during total intravenous anesthesia for atrial fibrillation ablation. BIS
      monitoring is a novel way to modulate anesthesia during ablation to potentially
      optimize patient comfort and ablation success.

PMID- 22366998
TI  - Female 'groin' hernia: totally extraperitoneal (TEP) endoscopic repair seems the
      most appropriate treatment modality.
AB  - BACKGROUND: About 30% of all female 'groin' hernias are femoral hernias, although
      often only diagnosed during surgery. A Lichtenstein repair though, as preferred
      treatment modality according to guidelines, would not diagnose and treat femoral
      hernias. Totally extraperitoneal (TEP) hernia repair, however, offers the
      advantage of being an appropriate modality for the diagnosis and subsequent
      treatment of both inguinal and femoral hernias. TEP therefore seems an appealing
      surgical technique for women with groin hernias. METHODS: This study included all
      female patients >= 18 years operated for a groin hernia between 2005 and 2009.
      RESULTS: A total of 183 groin hernias were repaired in 164 women. TEP was
      performed in 85% of women; the other 24 women underwent an open anterior (mesh)
      repair. Peroperatively, femoral hernias were observed in 23% of patients with
      primary hernias and 35% of patients with recurrent hernias. There were 30 cases
      (18.3%) of an incorrect preoperative diagnosis. Peroperatively, femoral hernias
      were observed in 17.3% of women who were diagnosed with an inguinal hernia before
      surgery. In addition, inguinal hernias were found in 24.0% of women who were
      diagnosed with a femoral hernia preoperatively. After a follow-up of 25 months,
      moderate to severe (VAS 4-10) postoperative pain was reported by 8 of 125
      patients (6.4%) after TEP and 5 of 23 patients (21.7%) after open hernia repair
      (P = 0.03). Five patients had a recurrent hernia, two following TEP (1.4%) and
      three following open anterior repair (12.5%, P = 0.02). Two of these three
      patients presented with a femoral recurrence after a previous repair of an
      inguinal hernia. CONCLUSION: Femoral hernias are common in women with groin
      hernias, but not always detected preoperatively; this argues for the use of a
      preperitoneal approach. TEP hernia repair combines the advantage of a
      peroperative diagnosis and subsequent appropriate treatment with the known good
      clinical outcomes.

PMID- 22366999
TI  - Comparison of four techniques for synoviocentesis of the equine digital flexor
      tendon sheath: a cadaveric study.
AB  - OBJECTIVE: To compare four different techniques for synoviocentesis of the equine
      digital flexor tendon sheath (DFTS). METHODS: Fifteen inexperienced operators
      performed each of the following injection techniques on two cadaveric limbs:
      Proximal (at the proximal recess of the DFTS), Axial (axial to the proximal
      sesamoid bone), Base (at the base of the proximal sesamoid bone), and Distal (at
      the pastern). The number of attempts needed before the needle was assumed to be
      correctly positioned into the DFTS was recorded and 10 ml of methylene blue was
      injected. The limbs were dissected to determine the presence of methylene blue in
      the DFTS, the distance between the needle entrance point and the lateral palmar
      or plantar (digital) nerve, the degree of subcutaneous leakage and the distance
      between the border of the leakage zone and the lateral digital nerve. RESULTS:
      The Axial (29/30) and Distal (25/30) approaches had the highest numbers of
      successful injections. The median number of attempts was highest for the Axial
      approach. The distances from the injection point and from the border of the
      leakage zone to the lateral digital nerve were longer for Distal and Axial
      approaches. CLINICAL RELEVANCE: In the hands of inexperienced operators, the
      Axial approach was the most successful technique for injection of the equine
      DFTS. Sparse subcutaneous leakage and larger distance to the nerve when using
      this technique might decrease the risk of in-advertent palmar or plantar digital
      nerve desensitisation when performing DFTS analgesia.

PMID- 22367000
TI  - Is there an objective way to compare research risks?
AB  - Determining whether a research risk meets or exceeds a regulatory standard of
      risk acceptability is difficult. Recently a framework called the systematic
      evaluation of research risks (SERR) has been proposed as a method of comparing
      research risks with predetermined standards of acceptability. SERR purports to
      offer a systematic and largely determinate (definite) way to compare risks and
      say whether a specific research risk falls below or above an acknowledged
      standard of acceptable risk. Here the authors review some philosophical problems
      with this framework, which they take to be representative of determinate
      approaches to risk comparison, and conclude that it should not be used in a stand
      alone or determinate fashion. Instead, the authors suggest that a deliberative
      approach may be a more viable candidate for future development. Such an approach
      could be informed by methods such as SERR without being rigidly bound to them.

PMID- 22367001
TI  - Postmortem brain donation and organ transplantation in schizophrenia: what about
      patient consent?
AB  - In patients with schizophrenia, consent postmortem for organ donation for
      transplantation and research is usually obtained from relatives. By means of a
      questionnaire, the authors investigate whether patients with schizophrenia would
      agree to family members making such decisions for them as well as compare
      decisions regarding postmortem organ transplantation and brain donation between
      patients and significant family members. Study results indicate while most
      patients would not agree to transplantation or brain donation for research, a
      proportion would agree. Among patients who declined organ donation for
      transplantation or brain research, almost half of family members would have
      agreed to brain donation for research and over 40% to organ transplantation. Male
      relatives are more likely to agree to organ donation from their deceased
      relatives for both transplantation and research. The authors argue that it is
      important to respect autonomy and interests of research subjects even if mentally
      ill and even if no longer living. Consent may be assisted by appropriate
      educational interventions prior to patient death.

PMID- 22367002
TI  - Gated three-terminal device architecture to eliminate persistent
      photoconductivity in oxide semiconductor photosensor arrays.
AB  - The composition of amorphous oxide semiconductors, which are well known for their
      optical transparency, can be tailored to enhance their absorption and induce
      photoconductivity for irradiation with green, and shorter wavelength light. In
      principle, amorphous oxide semiconductor-based thin-film photoconductors could
      hence be applied as photosensors. However, their photoconductivity persists for
      hours after illumination has been removed, which severely degrades the response
      time and the frame rate of oxide-based sensor arrays. We have solved the problem
      of persistent photoconductivity (PPC) by developing a gated amorphous oxide
      semiconductor photo thin-film transistor (photo-TFT) that can provide direct
      control over the position of the Fermi level in the active layer. Applying a
      short-duration (10 ns) voltage pulse to these devices induces electron
      accumulation and accelerates their recombination with ionized oxygen vacancy
      sites, which are thought to cause PPC. We have integrated these photo-TFTs in a
      transparent active-matrix photosensor array that can be operated at high frame
      rates and that has potential applications in contact-free interactive displays.

PMID- 22367003
TI  - Anisotropic conductance at improper ferroelectric domain walls.
AB  - Transition metal oxides hold great potential for the development of new device
      paradigms because of the field-tunable functionalities driven by their strong
      electronic correlations, combined with their earth abundance and environmental
      friendliness. Recently, the interfaces between transition-metal oxides have
      revealed striking phenomena, such as insulator-metal transitions, magnetism,
      magnetoresistance and superconductivity. Such oxide interfaces are usually
      produced by sophisticated layer-by-layer growth techniques, which can yield high
      quality, epitaxial interfaces with almost monolayer control of atomic positions.
      The resulting interfaces, however, are fixed in space by the arrangement of the
      atoms. Here we demonstrate a route to overcoming this geometric limitation. We
      show that the electrical conductance at the interfacial ferroelectric domain
      walls in hexagonal ErMnO(3) is a continuous function of the domain wall
      orientation, with a range of an order of magnitude. We explain the observed
      behaviour using first-principles density functional and phenomenological
      theories, and relate it to the unexpected stability of head-to-head and tail-to
      tail domain walls in ErMnO(3) and related hexagonal manganites. As the domain
      wall orientation in ferroelectrics is tunable using modest external electric
      fields, our finding opens a degree of freedom that is not accessible to spatially
      fixed interfaces.

PMID- 22367005
TI  - Reversible electrical switching of spin polarization in multiferroic tunnel
      junctions.
AB  - Spin-polarized transport in ferromagnetic tunnel junctions, characterized by
      tunnel magnetoresistance, has already been proven to have great potential for
      application in the field of spintronics and in magnetic random access memories.
      Until recently, in such a junction the insulating barrier played only a passive
      role, namely to facilitate electron tunnelling between the ferromagnetic
      electrodes. However, new possibilities emerged when ferroelectric materials were
      used for the insulating barrier, as these possess a permanent dielectric
      polarization switchable between two stable states. Adding to the two different
      magnetization alignments of the electrode, four non-volatile states are therefore
      possible in such multiferroic tunnel junctions. Here, we show that owing to the
      coupling between magnetization and ferroelectric polarization at the interface
      between the electrode and barrier of a multiferroic tunnel junction, the spin
      polarization of the tunnelling electrons can be reversibly and remanently
      inverted by switching the ferroelectric polarization of the barrier. Selecting
      the spin direction of the tunnelling electrons by short electric pulses in the
      nanosecond range rather than by an applied magnetic field enables new
      possibilities for spin control in spintronic devices.

PMID- 22367004
TI  - Self-assembled RNA interference microsponges for efficient siRNA delivery.
AB  - The encapsulation and delivery of short interfering RNA (siRNA) has been realized
      using lipid nanoparticles, cationic complexes, inorganic nanoparticles, RNA
      nanoparticles and dendrimers. Still, the instability of RNA and the relatively
      ineffectual encapsulation process of siRNA remain critical issues towards the
      clinical translation of RNA as a therapeutic. Here we report the synthesis of a
      delivery vehicle that combines carrier and cargo: RNA interference (RNAi)
      polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which
      in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of
      cleavable RNA strands, and are processed by the cell's RNA machinery to convert
      the stable hairpin RNA to siRNA only after cellular uptake, thus inherently
      providing protection for siRNA during delivery and transport to the cytoplasm.
      More than half a million copies of siRNA can be delivered to a cell with the
      uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic
      routes for siRNA delivery.

PMID- 22367006
TI  - Highly oriented surface-growth and covalent dye labeling of mesoporous metal
      organic frameworks.
AB  - Mesoporous amino-functionalized metal-organic framework thin films with the UiO
      68 topology were grown in a highly oriented fashion on two different self
      assembled monolayers on gold. The oriented MOF films were covalently modified
      with the fluorescent dye Rhodamine B inside the pore system, as demonstrated with
      size-selective fluorescence quenching studies. Our study suggests that mesoporous
      metal-organic frameworks are promising hosts for the covalent attachment of
      numerous functional moieties in a molecularly designed crystalline environment.

PMID- 22367007
TI  - Superiority of bridging techniques with medial fixation on initial strength.
AB  - PURPOSE: The purpose of our study was to evaluate the initial fixation strength
      of bridging techniques compared to other suture techniques for rotator cuff
      repair using a biomechanical animal model, which incorporated pretesting of
      intact tendons. METHODS: Seventy-six fresh bovine shoulders were used for testing
      seven suture configurations including simple suture (SS), mattress suture (MS),
      Mason-Allen (MA), modified double row (mDR), SpeedBridge (SpB), SpeedBridge with
      medial fixation (mSpB), and double-mattress SutureBridge (dmSuB) techniques.
      Cyclic loading was performed with all intact bone-tendon complex before (pretest)
      and after repair of the tendon (main test) at the level of 10 and 180 N at 100 Hz
      with displacement-controlled ramps of +/- 33 mm/s. The pretest was stopped after
      200 cycles. For the main test, the loading scheme was continued for a maximum of
      500 cycles or until failure. RESULTS: The mean elongation of all 76 intact
      tendons measured at the pretest was 3.8 +/- 0.6 mm (2.4-5.4 mm). No differences
      of gap formations at the 1st cycle were detected between SS, MS, MA, and mDR. SpB
      showed significant higher gap formations compared to all other suture techniques
      (p = 0.001). No significant differences were detected between mSpB and dmSuB,
      whereas both techniques were significant different when compared to the other
      groups (p < 0.05). CONCLUSIONS: In this study, results showed that bridging
      techniques with medial fixations have superior initial repair strength compared
      to other suture techniques. Knowledge of initial fixation strength of rotator
      cuff repair techniques may be of informative value to the surgeon.

PMID- 22367008
TI  - IFSO-APC consensus statements 2011.
AB  - Associations of BMI with body composition and health outcomes may differ between
      Asian and European populations. Asian populations have also been shown to have an
      elevated risk of type 2 diabetes, hypertension, and hyperlipidemia at a
      relatively low level of BMI. New surgical indication for Asian patients should be
      discussed by the expert of this field. Forty-four bariatric experts in Asia
      Pacific and other regions were chosen to have a voting privilege for IFSO-APC
      Consensus at the 2nd IFSO-APC Congress. A computerized audience-response voting
      system was used to analyze the agreement with the sentence of the consensus. Of
      all delegates, 95% agreed with the necessity of the establishment of IFSO-APC
      consensus statements, and 98% agreed with the necessity of a new indication for
      Asian patients. IFSO-APC Consensus statements 2011. Bariatric surgery should be
      considered for the treatment of obesity for acceptable Asian candidates with BMI
      >= 35 with or without co-morbidities. Bariatric/GI metabolic surgery should be
      considered for the treatment of T2DM or metabolic syndrome for patients who are
      inadequately controlled by lifestyle alternations and medical treatment for
      acceptable Asian candidates with BMI >= 30. The surgical approach may be
      considered as a non-primary alternative to treat inadequately controlled T2DM, or
      metabolic syndrome, for suitable Asian candidates with BMI >= 27.5. Other eight
      sentences are agreed with by majority of the voting delegates to form IFSO-APC
      consensus statements. This will help to make safe and wholesome the progress of
      bariatric and metabolic surgery in Asia.

PMID- 22367009
TI  - Ghrelin suppression and fat loss after left gastric artery embolization in canine
      model.
AB  - PURPOSE: To evaluate the effects of left gastric artery embolization (LGAE) on
      plasma ghrelin levels, abdominal fat, and body weight in beagles. METHODS: The
      institutional animal care and use committee approved this study. Fifteen healthy
      adult beagles (12 male and three female animals) were randomly divided into three
      experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A(5)
      hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B).
      Transcatheter saline injections in the left gastric artery were performed as a
      control. Weight and fasting plasma ghrelin levels were obtained at baseline and
      at weekly intervals for 8 weeks after the procedure in all animals. All animals
      were scanned and measured by multidetector computed tomography at baseline and at
      week 8 for evaluation of abdominal fat. RESULTS: In LGAE-treated animals, plasma
      ghrelin and body weight significantly decreased compared to control animals
      (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000,
      respectively). Subcutaneous fat size was also significantly reduced (P = 0.011
      and P = 0.027 for groups A and B, respectively). The decreasing percentage in
      ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were
      negatively correlated with the size of area supplied by left gastric artery (r = 
      0.693, P = 0.026). CONCLUSION: LGAE could suppress the plasma concentration of
      ghrelin, which results in subcutaneous fat size reduction and weight loss.
      Compensatory ghrelin production might occur in the remnant gastric fundus after
      LGAE.

PMID- 22367010
TI  - Irreversible electroporation for focal ablation at the porta hepatis.
AB  - Patients with chemotherapy-refractory liver metastases who are not candidates for
      surgery may be treated with focal ablation techniques with established survival
      benefits. Irreversible electroporation is the newest of these and has the
      putative advantages of a nonthermal action, preventing damage to adjacent biliary
      structures and bowel. This report describes the use of irreversible
      electroporation in a 61-year-old man with a solitary chemoresistant liver
      metastasis unsuitable for radiofrequency ablation as a result of its proximity to
      the porta hepatis. At 3 months, tumor size was decreased on computed tomography
      from 28 * 19 to 20 * 17 mm, representing stable disease according to the response
      evaluation criteria in solid tumors. This corresponded to a decrease in tumor
      volume size from 5.25 to 3.16 cm(3). There were no early or late complications.
      Chemoresistant liver metastases in the proximity of the porta hepatis that are
      considered to be too high a risk for conventional surgery or thermal ablation may
      be considered for treatment by the novel ablation technique of irreversible
      electroporation.

PMID- 22367011
TI  - Heart rate variability in elite triathletes, is variation in variability the key
      to effective training? A case comparison.
AB  - Measures of an athlete's heart rate variability (HRV) have shown potential to be
      of use in the prescription of training. However, little data exists on elite
      athletes who are regularly exposed to high training loads. This case study
      monitored daily HRV in two elite triathletes (one male: 22 year, VO2max 72.5 ml
      kg min(-1); one female: 20 year, VO2max 68.2 ml kg min(-1)) training 23 +/- 2 h
      per week, over a 77-day period. During this period, one athlete performed poorly
      in a key triathlon event, was diagnosed as non-functionally over-reached (NFOR)
      and subsequently reactivated the dormant virus herpes zoster (shingles). The 7
      day rolling average of the log-transformed square root of the mean sum of the
      squared differences between R-R intervals (Ln rMSSD), declined towards the day of
      triathlon event (slope = -0.17 ms/week; r2 = -0.88) in the NFOR athlete,
      remaining stable in the control (slope = 0.01 ms/week; r2 = 0.12). Furthermore,
      in the NFOR athlete, coefficient of variation of HRV (CV of Ln rMSSD 7-day
      rolling average) revealed large linear reductions towards NFOR (i.e., linear
      regression of HRV variables versus day number towards NFOR: -0.65%/week and r2 = 
      0.48), while these variables remained stable for the control athlete (slope =
      0.04%/week). These data suggest that trends in both absolute HRV values and day
      to-day variations may be useful measurements indicative of the progression
      towards mal-adaptation or non-functional over-reaching.

PMID- 22367014
TI  - Toward an ethical eugenics: the case for mandatory preimplantation genetic
      selection.
AB  - Preimplantation genetic diagnosis offers the possibility of screening and
      terminating embryos with severe and life-threatening disabilities. This article
      argues that under certain conditions, the use of this technology is not merely
      desirable as a means to reduce human suffering but also an ethically required
      duty of a parent to a potential child.

PMID- 22367015
TI  - Practice patterns of licensed practical nurses in North Carolina.
AB  - In the United States, state laws develop basic practices to define the scopes of
      practice for registered nurses and licensed practical nurses (LPNs). The purpose
      of the study was to describe the actual practice patterns of LPNs working in
      North Carolina. The results of the study convey an unfavorable pattern regarding
      LPN scope of practice. Indications are that a paradigm shift might be required in
      order to reverse the pattern of overpractice by LPNs.

PMID- 22367016
TI  - Living kidney donor advocacy program: a quality improvement project.
AB  - OBJECTIVE: : In 2007, the Centers for Medicare & Medicaid Services mandated that
      kidney transplant programs establish a living donor advocate program to ensure
      safe care and support for living organ donors. This quality improvement project
      assessed the impact of establishing a living donor advocate program and
      identified the ethical commitments and threats living kidney donors perceive
      throughout the donation process. METHOD: : This quality improvement project
      reflects a mixed-methods methodology. Qualitative as well as quantitative data
      were generated through the donor-advocate consultation sessions and the written
      Living Donor Satisfaction Survey. Thirteen living donors participated. RESULTS: :
      No threats to donor rights were identified by either the donor or the advocate.
      Nonrelated donors were motivated by altruism, whereas related donors were
      motivated by a sense of family. A majority of donors reported being changed
      emotionally and spiritually by the act of serving as a living donor. The living
      kidney donors were overwhelmingly extremely satisfied with their decision to
      donate and perceived the living donor advocacy program as being very good.
      DISCUSSION: : Questions have been raised about what role the donor's spouse
      should have during the informed consent process. Further research is needed to
      better understand the role and power of an advocate when threats to the donor's
      rights are noted.

PMID- 22367017
TI  - Living kidney donor advocacy program:  a quality improvement project.

PMID- 22367018
TI  - Investigating friendship quality: an exploration of self-control and social
      control theories' friendship hypotheses.
AB  - While associations with deviant peers are well understood to impact individual
      development, less is understood about the relationship between friendship quality
      and delinquency. Two criminological theories--social control theory and self
      control theory--are able to offer an explanation for the latter relationship.
      Social control and self-control theories both premise that delinquents will have
      largely fractured, weak, and "cold and brittle" friendships. This study
      investigates how variations in perceptions of friendship quality are related to
      the delinquency, maternal attachment, school attachment, and self-control levels
      of both a participant and his/her close friend. To explore these relationships,
      we use a diverse (14% black; 18% Hispanic; 9% Asian) sample of 2,154 emerging
      adults within 1,077 friendship pairs (66% female). In each dyad, both members
      perceived the friendship's quality and reported personal markers of delinquency,
      social bonds, and self-control. Several series of multilevel models are estimated
      that regress each participant's friendship quality perception onto the
      participant's and their friend's delinquency, attachments, self-control, and
      demographic characteristics. Results show that delinquents have as intense, or
      more intense, friendships as non-delinquents. However, low levels of both actor
      and partner attachments and self-control are independently related to low
      friendship quality, and this is especially true for self-control. Supplemental
      analyses demonstrate that the effect of self-control on friendship quality may be
      reduced when individuals in dyads are delinquent. In conclusion, studies that
      address friendship quality without including characteristics of multiple members
      of the friendship are only capturing part of one's estimate of friendship
      quality.

PMID- 22367019
TI  - Real-time monitoring of adherent Vero cell density and apoptosis in bioreactor
      processes.
AB  - This study proposes an easy to use in situ device, based on multi-frequency
      permittivity measurements, to monitor the growth and death of attached Vero cells
      cultivated on microporous microcarriers, without any cell sampling. Vero cell
      densities were on-line quantified up to 10(6) cell mL(-1). Some parameters which
      could potentially impact Vero cell morphological and physiological states were
      assessed through different culture operating conditions, such as media
      formulation or medium feed-harvest during cell growth phase. A new method of in
      situ cell death detection with dielectric spectroscopy was also successfully
      implemented. Thus, through permittivity frequency scanning, major rises of the
      apoptotic cell population in bioreactor cultures were detected by monitoring the
      characteristic frequency of the cell population, f(c), which is one of the
      culture dielectric parameters. Both cell density quantification and cell
      apoptosis detection are strategic information in cell-based production processes
      as they are involved in major events of the process, such as scale-up or choice
      of the viral infection conditions. This new application of dielectric
      spectroscopy to adherent cell culture processes makes it a very promising tool
      for risk-mitigation strategy in industrial processes. Therefore, our results
      contribute to the development of Process Analytical Technology in cell-based
      industrial processes.

PMID- 22367020
TI  - The isolation and characterization of putative mesenchymal stem cells from the
      spiny mouse.
AB  - The bone marrow represents the most common source from which to isolate
      mesenchymal stem cells (MSCs). MSCs are capable of differentiating into tissues
      of the three primary lineages and have the potential to enhance repair in damaged
      organs through the principals of regenerative medicine. Given the ease with which
      MSCs may be isolated from different species the aim of this study was to isolate
      and characterize putative bone marrow derived MSCs from the spiny mouse, Acomys
      cahirinus. MSCs were isolated from the spiny mouse in a traditional manner, and
      based on plastic adherence, morphology, colony forming unit-fibroblast assays and
      functional assessment (adipogenic, osteogenic and chondrogenic differentiation
      potential) a population of putative mesenchymal stem cells from the compact bone
      of the spiny mouse have been isolated and characterized. Such methodological
      approaches overcome the lack of species-specific antibodies for the spiny mouse
      and could be employed for other species where the cost of generating species
      specific antibodies is not warranted.

PMID- 22367021
TI  - High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase
      esophageal cancer risk.
AB  - Esophageal cancer (EC) has a globally increasing incidence with poor curative
      treatment options and survival rates. Environmental and dietary factors have
      crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a
      superfamily of enzymes essential for the detoxification of carcinogens, may alter
      enzyme activity and subsequently may play a role in EC etiology. Rather than
      solely establishing differences in genotype distribution, we investigated whether
      functional polymorphisms in UGT genes that can predict enzyme activity in vivo,
      may influence EC risk. A case-control study including 351 Caucasian EC patients
      and 592 Caucasian controls was conducted and polymorphisms in seven UGT genes
      were determined, using the polymerase chain reaction. On the basis of allelic in
      vitro enzyme activity measurements, genotypes were categorized according to their
      predicted in vivo enzyme activity into high, medium and low categories. Predicted
      enzyme activity groups were combined and compared between patients and controls.
      The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly
      more (OR=1.62; 95% CI, 1.02-2.56) and less frequent (OR=0.36; 95% CI, 0.15-0.84)
      among patients with esophageal squamous cell carcinoma (ESCC), respectively. High
      (OR=0.42; 95% CI, 0.22-0.84) and medium (OR=0.25; 95% CI, 0.12-0.52) activity
      UGT2B4 genotypes were significantly less often present in ESCC patients. No
      association was detected between UGT genotypes and esophageal adenocarcinoma
      (EAC) risk. Polymorphisms in UGT genes, resulting in altered enzyme activity
      genotypes, do not seem modifiers of EAC risk. However, the predicted high
      activity UGT1A1 genotype, associated with low serum levels of the antioxidant
      bilirubin, was associated with an increased ESCC risk. The UGT1A8 and UGT2B4
      genotypes associated with decreased predicted enzyme activities, were
      significantly associated with an increased risk of ESCC, probably by a decreased
      detoxification of carcinogens.

PMID- 22367022
TI  - Metadherin regulates radioresistance in cervical cancer cells.
AB  - Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and
      angiogenesis. Upregulation of MTDH is correlated with both progression and poor
      clinical outcome of many types of cancers; however, there is currently no
      information regarding the role of MTDH in radiation sensitivity. Here, we
      investigated the effects of MTDH on the radiosensitivity of cervical cancer cells
      using the SiHa cell line. We discovered that cervical cancer cells in which MTDH
      was knocked down had significantly increased radiosensitivity as measured by a
      clonogenic assay. MTDH knockdown cells also had increased apoptosis and a
      decreased proportion of cells arrested in the G2 phase after radiation treatment.
      MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs)
      induced by radiation. These results indicate that MTDH affects the
      radiosensitivity of cervical cancer cells and that MTDH may be a novel target to
      improve cervical cancer radiation response.

PMID- 22367023
TI  - Determination of the volatile composition in brown millet, milled millet and
      millet bran by gas chromatography/mass spectrometry.
AB  - The volatile compounds from brown millet (BM), milled millet (MM) and millet bran
      (MB) were extracted using simultaneous distillation/extraction with a Likens
      Nickerson apparatus. The extracts were analysed using gas chromatography coupled
      with mass spectrometry (GC-MS). A total of 65 volatile compounds were identified
      in all of the samples. Among these compounds, 51, 51 and 49 belonged to BM, MM
      and MB, respectively. Aldehydes and benzene derivatives were the most numerous
      among all of the compounds. Three compounds (hexanal, hexadecanoic acid and 2
      methylnaphthalene) were dominant in the BM and MM materials. Eight compounds
      (hexanal, nonanal, (E)-2-nonenal, naphthalene, 2-methylnaphthalene, 1
      methylnaphthalene, hexadecanoic acid and 2-pentylfuran) were dominant in the MB
      materials. Apart from the aromatic molecules, which were present in all
      fractions, compounds present only in BM, MM or MB were also identified.

PMID- 22367024
TI  - Evaluation of rheological properties and swelling behaviour of sonicated
      scleroglucan samples.
AB  - Scleroglucan is a natural polysaccharide that has been proposed for various
      applications. However there is no investigation on its property variations when
      the molecular weight of this polymer is reduced. Scleroglucan was sonicated at
      two different polymer concentrations for different periods of time and the effect
      of sonication was investigated with respect to molecular weight variations and
      rheological properties. Molar mass, estimated by viscometric measurements, was
      drastically reduced already after a sonication for a few min. Sonicated samples
      were used for the preparation of gels in the presence of borate ions. The effect
      of borax on the new samples was investigated by recording the mechanical spectra
      and the flow curves. A comparison with the system prepared with the dialysed
      polymer was also carried out. The anisotropic elongation, observed with tablets
      of scleroglucan and borax, was remarkably reduced when the sonicated samples were
      used for the preparation of the gels.

PMID- 22367025
TI  - Experimental methodologies and evaluations of computer-aided drug design
      methodologies applied to a series of 2-aminothiophene derivatives with antifungal
      activities.
AB  - Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives
      were screened for their in vitro antifungal activities against Candida krusei and
      Cryptococcus neoformans. Based on experimentally determined minimum inhibitory
      concentration (MIC) values, we conducted computer-aided drug design studies
      [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable
      the prediction of three-dimensional structural characteristics that influence the
      antifungal activities of these derivatives. These predictions provide direction
      with regard to the syntheses of new derivatives with improved biological
      activities, which can be used as therapeutic alternatives for the treatment of
      fungal infections.

PMID- 22367026
TI  - Acylated mono-, bis- and tris- cinchona-based amines containing ferrocene or
      organic residues: synthesis, structure and in vitro antitumor activity on
      selected human cancer cell lines.
AB  - A series of novel functionalized mono-, bis- and tris-(S)-{[(2S,4R,8R)-8-ethyl
      quinuclidin-2-yl](6-methoxyquinolin-4-yl)}methanamines including ferrocene
      containing derivatives was obtained by the reaction of the precursor amine with a
      variety of acylation agents. Their in vitro antitumor activity was investigated
      against human leukemia (HL-60), human neuroblastoma (SH-SY5Y), human hepatoma
      (HepG2) and human breast cancer (MCF-7) cells by the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT)-assay and the 50% inhibitory concentration
      (IC(50)) values were determined. Our data indicate that the precursor amine has
      no antitumor activity in vitro, but the bis-methanamines with ureido-, thioureido
      and amide-type linkers display attractive in vitro cytotoxicity and cytostatic
      effects on HL-60, HepG2, MCF-7 and SH-SY5Y cells. Besides 1H- and 13C-NMR methods
      the structures of the new model compounds were also studied by DFT calculations.

PMID- 22367027
TI  - Determination of antimicrobial activity and resistance to oxidation of moringa
      peregrina seed oil.
AB  - The antimicrobial activity of the oil extracted with n-hexane from the seeds of
      Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis,
      Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella
      pneumoniae, Candida albicans, C. tropicalis and C. glabrata. The oil proved
      effective against all of the tested microorganisms. Standard antibiotics
      (netilmycin, 5-flucytocine, intraconazole and 7-amino-4-methylcoumarin-3-acetic
      acid) were used for comparison. The resistance to oxidation of the extracted seed
      oil was also determined.

PMID- 22367028
TI  - Comparative Studies of the (Anti) Mutagenicity of Baccharis dracunculifolia and
      Artepillin C by the Bacterial Reverse Mutation Test.
AB  - Baccharis dracunculifolia is a plant native from Brazil, commonly known as
      'Alecrim-do-campo' and 'Vassoura' and used in alternative medicine for the
      treatment of inflammation, hepatic disorders and stomach ulcers. Previous studies
      reported that artepillin C (ArtC, 3-{4-hydroxy-3,5-di(3-methyl-2-butenyl)phenyl}
      2(E)-propenoic acid), is the main compound of interest in the leaves. This study
      was undertaken to assess the mutagenic effect of the ethyl acetate extract of B.
      dracunculifolia leaves (Bd-EAE: 11.4-182.8 ug/plate) and ArtC (0.69-10.99
      ug/plate) by the Ames test using Salmonella typhimurium strains TA98, TA97a,
      TA100 and TA102, and to compare the protective effects of Bd-EAE and ArtC against
      the mutagenicity of a variety of direct and indirect acting mutagens such as 4
      nitro-O-phenylenediamine, sodium azide, mitomycin C, benzo[a]pyrene, aflatoxin
      B1,  2-aminoanthracene and 2-aminofluorene.The mutagenicity test showed that Bd
      EAE and ArtC did not induce an increase in the number of revertant colonies
      indicating absence of mutagenic activity. ArtC showed a similar antimutagenic
      effect to that of Bd-EAE in some strains of S. typhimurium, demonstrating that
      the antimutagenic activity of Bd-EAE can be partially attributed to ArtC. The
      present results showed that the protective effect of whole plant extracts is due
      to the combined and synergistic effects of a complex mixture of phytochemicals,
      the total activity of which may result in health benefits.

PMID- 22367029
TI  - Syntheses and cell-based phenotypic screen of novel 7-amino pyrido[2,3
      d]pyrimidine-6-carbonitrile derivatives as potential antiproliferative agents.
AB  - A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile
      derivatives was readily synthesized and their anti-proliferative activities on
      five types of tumor cells were evaluated through a cell-based phenotypic
      screening approach. Compound 3k was found to be potent on human colon cancer
      SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound
      3k led to compound 4a with improved anti-proliferative potency on SW620 cells
      with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that
      compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

PMID- 22367030
TI  - Beauvericin, a bioactive compound produced by fungi: a short review.
AB  - Beauvericin is a cyclic hexadepsipeptide mycotoxin, which has insecticidal,
      antimicrobial, antiviral and cytotoxic activities. It is a potential agent for
      pesticides and medicines. This paper reviews the bioactivity, fermentation and
      biosynthesis of the fungal product beauvericin.

PMID- 22367031
TI  - Serial founder effects during range expansion: a spatial analog of genetic drift.
AB  - Range expansions cause a series of founder events. We show that, in a one
      dimensional habitat, these founder events are the spatial analog of genetic drift
      in a randomly mating population. The spatial series of allele frequencies created
      by successive founder events is equivalent to the time series of allele
      frequencies in a population of effective size ke, the effective number of
      founders. We derive an expression for ke in a discrete-population model that
      allows for local population growth and migration among established populations.
      If there is selection, the net effect is determined approximately by the product
      of the selection coefficients and the number of generations between successive
      founding events. We use the model of a single population to compute analytically
      several quantities for an allele present in the source population: (i) the
      probability that it survives the series of colonization events, (ii) the
      probability that it reaches a specified threshold frequency in the last
      population, and (iii) the mean and variance of the frequencies in each
      population. We show that the analytic theory provides a good approximation to
      simulation results. A consequence of our approximation is that the average
      heterozygosity of neutral alleles decreases by a factor of 1-1/(2ke) in each new
      population. Therefore, the population genetic consequences of surfing can be
      predicted approximately by the effective number of founders and the effective
      selection coefficients, even in the presence of migration among populations. We
      also show that our analytic results are applicable to a model of range expansion
      in a continuously distributed population.

PMID- 22367033
TI  - Computationally efficient sibship and parentage assignment from multilocus marker
      data.
AB  - Quite a few methods have been proposed to infer sibship and parentage among
      individuals from their multilocus marker genotypes. They are all based on
      Mendelian laws either qualitatively (exclusion methods) or quantitatively
      (likelihood methods), have different optimization criteria, and use different
      algorithms in searching for the optimal solution. The full-likelihood method
      assigns sibship and parentage relationships among all sampled individuals
      jointly. It is by far the most accurate method, but is computationally
      prohibitive for large data sets with many individuals and many loci. In this
      article I propose a new likelihood-based method that is computationally efficient
      enough to handle large data sets. The method uses the sum of the log likelihoods
      of pairwise relationships in a configuration as the score to measure its
      plausibility, where log likelihoods of pairwise relationships are calculated only
      once and stored for repeated use. By analyzing several empirical and many
      simulated data sets, I show that the new method is more accurate than pairwise
      likelihood and exclusion-based methods, but is slightly less accurate than the
      full-likelihood method. However, the new method is computationally much more
      efficient than the full-likelihood method, and for the cases of both sexes
      polygamous and markers with genotyping errors, it can be several orders faster.
      The new method can handle a large sample with thousands of individuals and the
      number of markers limited only by the computer memory.

PMID- 22367032
TI  - Homologous recombination via synthesis-dependent strand annealing in yeast
      requires the Irc20 and Srs2 DNA helicases.
AB  - Synthesis-dependent strand-annealing (SDSA)-mediated homologous recombination
      replaces the sequence around a DNA double-strand break (DSB) with a copy of a
      homologous DNA template, while maintaining the original configuration of the
      flanking regions. In somatic cells at the 4n stage, Holliday-junction-mediated
      homologous recombination and nonhomologous end joining (NHEJ) cause crossovers
      (CO) between homologous chromosomes and deletions, respectively, resulting in
      loss of heterozygosity (LOH) upon cell division. However, the SDSA pathway
      prevents DSB-induced LOH. We developed a novel yeast DSB-repair assay with two
      discontinuous templates, set on different chromosomes, to determine the genetic
      requirements for somatic SDSA and precise end joining. At first we used our in
      vivo assay to verify that the Srs2 helicase promotes SDSA and prevents imprecise
      end joining. Genetic analyses indicated that a new DNA/RNA helicase gene, IRC20,
      is in the SDSA pathway involving SRS2. An irc20 knockout inhibited both SDSA and
      CO and suppressed the srs2 knockout-induced crossover enhancement, the mre11
      knockout-induced inhibition of SDSA, CO, and NHEJ, and the mre11-induced
      hypersensitivities to DNA scissions. We propose that Irc20 and Mre11 functionally
      interact in the early steps of DSB repair and that Srs2 acts on the D-loops to
      lead to SDSA and to prevent crossoverv.

PMID- 22367034
TI  - Haploidization in Saccharomyces cerevisiae induced by a deficiency in homologous
      recombination.
AB  - Diploid Saccharomyes cerevisae strains lacking the RAD52 gene required for
      homologous recombination have a very high rate of chromosome loss. Two of four
      isolates subcultured ~20 times (~500 cell divisions) became haploid. These
      strains were capable of mating with wild-type haploids to produce diploid progeny
      capable of undergoing meiosis to produce four viable spores.

PMID- 22367035
TI  - Temperature-sensitive and circadian oscillators of Neurospora crassa share
      components.
AB  - In Neurospora crassa, the interactions between products of the frequency (frq),
      frequency-interacting RNA helicase (frh), white collar-1 (wc-1), and white collar
      2 (wc-2) genes establish a molecular circadian clockwork, called the FRQ-WC
      Oscillator (FWO), which is required for the generation of molecular and overt
      circadian rhythmicity. In strains carrying nonfunctional frq alleles, circadian
      rhythms in asexual spore development (conidiation) are abolished in constant
      conditions, yet conidiation remains rhythmic in temperature cycles. Certain
      characteristics of these temperature-synchronized rhythms have been attributed to
      the activity of a FRQ-less oscillator (FLO). The molecular components of this FLO
      are as yet unknown. To test whether the FLO depends on other circadian clock
      components, we created a strain that carries deletions in the frq, wc-1, wc-2,
      and vivid (vvd) genes. Conidiation in this DeltaFWO strain was still synchronized
      to cyclic temperature programs, but temperature-induced rhythmicity was distinct
      from that seen in single frq knockout strains. These results and other evidence
      presented indicate that components of the FWO are part of the temperature-induced
      FLO.

PMID- 22367036
TI  - Using the Genetics Concept Assessment to document persistent conceptual
      difficulties in undergraduate genetics courses.
AB  - To help genetics instructors become aware of fundamental concepts that are
      persistently difficult for students, we have analyzed the evolution of student
      responses to multiple-choice questions from the Genetics Concept Assessment. In
      total, we examined pretest (before instruction) and posttest (after instruction)
      responses from 751 students enrolled in six genetics courses for either majors or
      nonmajors. Students improved on all 25 questions after instruction, but to
      varying degrees. Notably, there was a subgroup of nine questions for which a
      single incorrect answer, called the most common incorrect answer, was chosen by
      >20% of students on the posttest. To explore response patterns to these nine
      questions, we tracked individual student answers before and after instruction and
      found that particular conceptual difficulties about genetics are both more likely
      to persist and more likely to distract students than other incorrect ideas. Here
      we present an analysis of the evolution of these incorrect ideas to encourage
      instructor awareness of these genetics concepts and provide advice on how to
      address common conceptual difficulties in the classroom.

PMID- 22367037
TI  - Tracing the emergence of a novel sex-determining gene in medaka, Oryzias
      luzonensis.
AB  - Three sex-determining (SD) genes, SRY (mammals), Dmy (medaka), and DM-W (Xenopus
      laevis), have been identified to date in vertebrates. However, how and why a new
      sex-determining gene appears remains unknown, as do the switching mechanisms of
      the master sex-determining gene. Here, we used positional cloning to search for
      the sex-determining gene in Oryzias luzonensis and found that GsdfY (gonadal soma
      derived growth factor on the Y chromosome) has replaced Dmy as the master sex
      determining gene in this species. We found that GsdfY showed high expression
      specifically in males during sex differentiation. Furthermore, the presence of a
      genomic fragment that included GsdfY converts XX individuals into fertile XX
      males. Luciferase assays demonstrated that the upstream sequence of GsdfY
      contributes to the male-specific high expression. Gsdf is downstream of Dmy in
      the sex-determining cascade of O. latipes, suggesting that emergence of the Dmy
      independent Gsdf allele led to the appearance of this novel sex-determining gene
      in O. luzonensis.

PMID- 22367038
TI  - In vivo role of alternative splicing and serine phosphorylation of the
      microphthalmia-associated transcription factor.
AB  - The microphthalmia-associated transcription factor (MITF) is a basic helix-loop
      helix leucine zipper protein that plays major roles in the development and
      physiology of vertebrate melanocytes and melanoma cells. It is regulated by post
      translational modifications, including phosphorylation at serine 73, which based
      on in vitro experiments imparts on MITF an increased transcriptional activity
      paired with a decreased stability. Serine 73 is encoded by the alternatively
      spliced exon 2B, which is preferentially skipped in mice carrying a targeted
      serine-73-to-alanine mutation. Here, we measured the relative abundance of exon
      2B+ and exon 2B- RNAs in freshly isolated and FACS-sorted wild-type melanoblasts
      and melanocytes and generated a series of knock-in mice allowing forced
      incorporation of either alanine, aspartate, or wild-type serine at position 73.
      None of these knock-in alleles, however, creates a striking pigmentation
      phenotype on its own, but differences between them can be revealed either by a
      general reduction of Mitf transcript levels or in heteroallelic combinations with
      extant Mitf mutations. In fact, compared with straight serine-73 knock-in mice
      with their relative reduction of 2B+ Mitf, forced incorporation of alanine 73
      leads to greater increases in MITF protein levels, melanoblast and melanocyte
      numbers, and extent of pigmentation in particular allelic combinations. These
      results underscore, in vivo, the importance of the link between alternative
      splicing and post-translational modifications and may bear on the recent
      observation that exon 2B skipping can be found in metastatic melanoma.

PMID- 22367039
TI  - Modulation of yeast alkaline cation tolerance by Ypi1 requires calcineurin.
AB  - Ypi1 was discovered as an essential protein able to act as a regulatory subunit
      of the Saccharomyces cerevisiae type 1 protein phosphatase Glc7 and play a key
      role in mitosis. We show here that partial depletion of Ypi1 causes lithium
      sensitivity and that high levels of this protein confer a lithium-tolerant
      phenotype to yeast cells. Remarkably, this phenotype was independent of the role
      of Ypi1 as a Glc7 regulatory subunit. Lithium tolerance in cells overexpressing
      Ypi1 was caused by a combination of increased efflux of lithium, mediated by
      augmented expression of the alkaline cation ATPase ENA1, and decreased lithium
      influx through the Trk1,2 high-affinity potassium transporters. Deletion of CNB1,
      encoding the regulatory subunit of the calcineurin phosphatase, blocked Ypi1
      induced expression of ENA1, normalized Li(+) fluxes, and abolished the Li(+)
      hypertolerant phenotype of Ypi1-overexpressing cells. These results point to a
      complex role of Ypi1 on the regulation of cation homeostasis, largely mediated by
      the calcineurin phosphatase.

PMID- 22367040
TI  - Genome scans for transmission ratio distortion regions in mice.
AB  - Transmission ratio distortion (TRD) is the departure from the expected genotypic
      frequencies under Mendelian inheritance. This departure can be due to multiple
      physiological mechanisms during gametogenesis, fertilization, fetal and embryonic
      development, and early neonatal life. Although a few TRD loci have been reported
      in mouse, inheritance patterns have never been evaluated for TRD. In this
      article, we developed a Bayesian binomial model accounting for additive and
      dominant deviation TRD mechanisms. Moreover, this model was used to perform
      genome-wide scans for TRD quantitative trait loci (QTL) on six F2 mouse crosses
      involving between 296 and 541 mice and between 72 and 1854 genetic markers.
      Statistical significance of each model was checked at each genetic marker with
      Bayes factors. Genome scans revealed overdominance TRD QTL located in mouse
      chromosomes 1, 2, 12, 13, and 14 and additive TRD QTL in mouse chromosomes 2, 3,
      and 15, although these results did not replicate across mouse crosses. This
      research contributes new statistical tools for the analysis of specific genetic
      patterns involved in TRD in F2 populations, our results suggesting a relevant
      incidence of TRD phenomena in mouse with important implications for both
      statistical analyses and biological research.

PMID- 22367041
TI  - Boston type I keratoprosthesis for visual rehabilitation in a patient with
      gelatinous drop-like corneal dystrophy.
AB  - PURPOSE: To report the use of a Boston type I keratoprosthesis as a primary
      penetrating procedure to treat gelatinous drop-like corneal dystrophy (GDLD),
      with presentation of pathologic findings and discussion of other surgical
      options. CASE REPORT: A 49-year-old woman with GDLD in both eyes and history of
      recurrent corneal opacification following multiple superficial keratectomies is
      presented. Best corrected visual acuity (BCVA) was counting fingers in both eyes.
      A Boston type I keratoprosthesis was implanted in her left eye after optical
      iridectomy, extracapsular cataract extraction, and anterior vitrectomy. RESULTS:
      The surgery was uneventful and one month after surgery, best corrected vision
      improved to 20/20 and has been maintained for a period of more than 14 months. No
      post-operative complications were observed. Histopathology of the corneal
      specimen is presented. CONCLUSIONS: GDLD is a rare disorder of amyloid
      deposition. Recurrence of this condition following surgery is extremely common.
      Boston type I keratoprosthesis is an effective procedure for restoring vision in
      affected patients.

PMID- 22367042
TI  - Visual outcomes of Boston keratoprosthesis implantation as the primary
      penetrating corneal procedure.
AB  - PURPOSE: To report the short-term visual outcomes and complications of
      keratoprosthesis surgery as the primary penetrating corneal procedure for
      patients at high risk for conventional corneal transplantation. METHODS: A
      retrospective chart review was conducted of 21 eyes of 19 patients who underwent
      either Boston keratoprosthesis type I or type II as the primary penetrating
      corneal procedure from February 2007 to March 2011. RESULTS: Nineteen type I
      (90.5%) and 2 type II (9.5%) Boston keratoprosthesis procedures were performed in
      19 patients. Mean follow-up was 14.6 months (range, 6-36.3 mo). Primary
      indications for surgery included chemical or thermal injury, aniridia, and
      Stevens-Johnson syndrome. Preoperative best-corrected visual acuity (BCVA) ranged
      from 20/100 to light perception and was count fingers or worse in 20 eyes
      (95.2%). At last follow-up for all eyes, 15 eyes (71.4%) achieved BCVA>=20/200
      and 4 eyes (19%) improved to BCVA>=20/50. No intraoperative complications
      occurred. Postoperative complications include retroprosthetic membrane formation
      (47.6%), cystoid macular edema (33.3%), elevated intraocular pressure (23.8%),
      glaucoma progression (14.3%), and endophthalmitis (4.8%). The initial
      keratoprosthesis was retained in 19 eyes (90.5%). CONCLUSION: The Boston
      keratoprosthesis, based on early follow-up, is a good alternative as a primary
      penetrating corneal procedure in a select group of patients with very poor
      prognosis for penetrating keratoplasty. Although complications can occur and
      require close monitoring, visual acuity significantly improved in the majority of
      patients.

PMID- 22367043
TI  - Corneal graft curvature change after relaxing incisions for post-penetrating
      keratoplasty astigmatism.
AB  - PURPOSE: To evaluate change in graft steepness after graft refractive surgery
      (GRS) consisting of relaxing incisions with or without counterquadrant
      compression sutures and discover the existing influential factors. METHODS: In
      this retrospective study, 78 eyes of 76 patients who had received penetrating
      keratoplasty for keratoconus underwent GRS because of high post-penetrating
      keratoplasty astigmatism. Any shift in graft curvature was calculated using the
      keratometric coupling ratio (CR; the ratio of flattening of the incised meridian
      to steepening of the opposite meridian). Multiple regression analysis was used to
      investigate the possible effect of age, graft curvature, number of incisions, use
      of compression sutures, achieved vector astigmatic correction, and total arc
      length on CR. RESULTS: Mean patient age was 30.1 +/- 10.3 years and mean follow
      up period after GRS was 40.1 +/- 29.0 months. There was a significant increase in
      average keratometry from 44.79 +/- 2.08 diopters (D) preoperatively to 45.65 +/-
      1.86 D postoperatively (P < 0.001). Mean keratometric CR was 0.62 +/- 1.09.
      Keratometric CR was significantly associated with patient age (R = 0.53, P =
      0.04) and preoperative average keratometry (R = 0.61, P = 0.02). However,
      keratometric CR failed to show any significant correlation with other variables.
      CONCLUSIONS: A significant increase in graft steepening occurred after GRS,
      averaging 0.86 D. When both GRS and cataract extraction or phakic intraocular
      lens implantation are indicated, a staged approach (first GRS followed by
      phacoemulsification, for example) is advocated to calculate intraocular lens
      power with accuracy.

PMID- 22367044
TI  - Comparison of central corneal thickness and anterior chamber depth measured using
      LenStar LS900, Pentacam, and Visante AS-OCT.
AB  - PURPOSE: To compare central corneal thickness (CCT) and anterior chamber depth
      (ACD) measured using 3 different techniques. METHODS: CCT and ACD were measured
      in one eye of 27 healthy subjects (age, mean +/- SD: 34 +/- 7 years), using the
      LenStar LS900, Pentacam, and Visante AS-OCT. The agreement between the
      measurement techniques was assessed using the coefficient of agreement (CoA) and
      the 95% limits of agreement (LoA). RESULTS: Mean +/- SD values for CCT using the
      LenStar, Pentacam, and Visante were 550.7 +/- 37.4 MUm, 542.7 +/- 37.9 MUm, and
      556.7 +/- 44.4 MUm, respectively (P = 0.005). Plots of differences against means
      displayed relatively good agreement between the Pentacam and LenStar (CoA, 19.97
      MUm; LoA, 15.53 MUm to -24.40 MUm), poorer agreement between the LenStar and
      Visante (CoA, 31.26 MUm; LoA, 40.78 MUm to -21.74 MUm), and agreement was poor
      between the Pentacam and Visante (CoA, 37.36 MUm; LoA, 25.61 MUm to -49.11 MUm).
      Mean +/- SD values for ACD using the LenStar, Pentacam, and Visante were 2.93 +/-
      0.30 mm, 2.96 +/- 0.32 mm, and 3.03 +/- 0.29 mm, respectively (P < 0.001).
      Relatively good agreement for ACD measures was observed between the Pentacam and
      LenStar (CoA, 0.08 mm; LoA, 0.12 to -0.04 mm), poor agreement was obtained
      between the Visante and LenStar (CoA, 0.13 mm; LoA, 0.21 to -0.06 mm), and
      agreement was also poor between the Pentacam and Visante (CoA, 0.14 mm; LoA, 0.11
      to -0.17 mm). CONCLUSIONS: Our data show that the LenStar, Pentacam, and Visante
      provide measurements that are in agreement with published values for CCT and ACD
      in human subjects. Although reasonable agreement for CCT and ACD was found
      between the Pentacam and LenStar, agreement was poorer between the Visante and
      LenStar and between the Visante and Pentacam. Thus, CCT and ACD measures from
      these instruments should not be used interchangeably.

PMID- 22367045
TI  - Expression of CXCL9, -10, and -11 in the aqueous humor of patients with herpetic
      endotheliitis.
AB  - PURPOSE: To evaluate the expression of CXCL9, -10, and -11 chemokines in the
      aqueous humor of patients with herpetic endotheliitis. METHODS: Aqueous humor was
      collected from 26 patients with herpetic endotheliitis and 21 control subjects.
      The concentrations of CXCL9, -10, and -11 in the aqueous humor were measured with
      enzyme-linked immunosorbent assays. The correlation between chemokine levels and
      clinical parameters of disease severity was analyzed. Flow cytometry was
      performed to count CXCR3 cells and CXCR3CD4 cells in the aqueous humor. RESULTS:
      The concentrations of CXCL9, -10, and -11 were 429.08 +/- 297.41 pg/mL, 23,102.49
      +/- 15,964.95 pg/mL, and 258.25 +/- 103.25 pg/mL in patients with herpetic
      endotheliitis and 16.84 +/- 16.73 pg/mL (P < 0.01), 188.45 +/- 183.43 pg/mL (P <
      0.01), and 7.32 +/- 6.45 pg/mL (P < 0.01) in control subjects, respectively.
      Aqueous chemokine levels correlated significantly with keratitic precipitates and
      corneal edema in patients with herpetic endotheliitis. The mean percentages of
      CXCR3 and CXCR3CD4 cells were higher in herpetic endotheliitis patients compared
      with the controls. CONCLUSIONS: Expression of CXCL9, -10, and -11 chemokines and
      their receptor CXCR3 increases in the aqueous humor of patients with herpetic
      endotheliitis. Chemokine levels are associated with the clinical severity of the
      disease.

PMID- 22367046
TI  - Prevalence and associations of external punctal stenosis in a general population
      in Spain.
AB  - PURPOSE: To determine the prevalence of external punctal stenosis (EPS) and to
      investigate its associations in a general adult population in northwestern Spain.
      METHODS: A total of 1155 subjects >= 40 years were selected by an age-stratified
      random sample procedure in O Salnes (Spain). An interview was carried out to
      collect history of systemic diseases and lifestyle details, and a comprehensive
      ophthalmic evaluation in which EPS was recorded. The prevalence of EPS and its
      relationship with demographic, lifestyle, and systemic and ocular factors was
      investigated. All calculations were weighted to give unbiased estimates. RESULTS:
      From 937 eligible subjects, 621 (66.3%) participated [mean age (SD), 63.4 (14.5)
      years; range, 40-96 years; 37.0% men). The prevalence of EPS was 17.3% [95%
      confidence interval (CI), 14.8-19.8). This prevalence increased significantly
      with aging (P = 0.000) and was 13.8% (95% CI, 10.3-18.3) in men and 19.4% (95%
      CI, 16.1-23.2) in women. After controlling for age and sex, EPS was associated
      with outdoor occupational activity (age and sex adjusted odd ratio [ORa], 2.22;
      95% CI, 1.31-3.37) and with degenerative disorders such as pinguecula (ORa, 1.48;
      95% CI, 1.15-1.89) but not with inflammatory disorders such as blepharitis or dry
      eye. A multivariable analysis in which sex differences also became significant (P
      = 0.024) confirmed these associations. CONCLUSIONS: External punctual stenosis is
      a common disorder associated with outdoor occupational activity. Processes
      associated with tissue degeneration but not with inflammation are highly
      prevalent among subjects with EPS. Modifiable factors, such as sun exposure, must
      be addressed to reduce the impact of this disorder.

PMID- 22367047
TI  - Endothelial keratoplasty: why aren't we all doing Descemet membrane endothelial
      keratoplasty?

PMID- 22367048
TI  - Big-bubble deep anterior lamellar keratoplasty assisted by femtosecond laser in
      children.
AB  - To report the early results of big-bubble deep anterior lamellar keratoplasty
      assisted by femtosecond laser in children. Five eyes of 5 pediatric patients were
      enrolled in the study; 3 had keratoconus and 2 corneal opacities. An IntraLase 60
      KHz femtosecond laser (Abbott Medical Optics, Inc) was used to create mushroom
      incisions on both donor and recipient corneas. All patients were evaluated for
      best-corrected visual acuity, spherical equivalent, refractive astigmatism,
      keratometric astigmatism, mean K value, and corneal thinnest point. The big
      bubble was always achieved, and all eyes were treated successfully without
      intraoperative complications. The follow-up was of 10 months. At 10 months (at
      least 3 months after complete suture removal), the mean postoperative best
      corrected visual acuity was 20/30 (range, 20/25 to 20/30), mean spherical
      equivalent was -1.8 +/- 1.2 diopters (D) (range, -0.25 to 1.25 D), mean
      refractive astigmatism was 1.8 +/- 1.4 D (range, 0 to 4.0 D), mean keratometric
      astigmatism was 5.1 +/- 2.1 D (range, 3.5 to 8.59 D), mean K value was 46.2 +/-
      0.8D, and mean corneal thinnest point was 581 +/- 46 MUm (range, 511-638 MUm).
      Our early findings suggest that the big-bubble technique in deep anterior
      lamellar keratoplasty assisted by femtosecond laser is safe and effective also in
      pediatric patients in the attempt to decrease the rejection percentage, improve
      the refractive outcome, and then provide an antiamblyopic effect.

PMID- 22367049
TI  - Therapeutic effect of intravitreal injection of triamcinolone in the treatment of
      endothelial graft rejection:  a pilot study.
AB  - PURPOSE: To investigate the efficacy of intravitreal triamcinolone acetonide
      (IVTA) injection in the treatment of endothelial graft rejection and the
      expression of T-helper type 1 (Th-1) chemokines in the aqueous humor. METHODS:
      Eleven patients (11 eyes) with acute endothelial graft rejection underwent IVTA
      (4 mg/0.1 mL) injection in addition to conventional treatment, including systemic
      and topical steroids and cyclosporine A (group A); 13 patients (13 eyes) received
      conventional treatment only (group B). Clinical characteristics were analyzed. In
      group A, Th-1 chemokines (CXCL-9, -10, and -11) in aqueous humor were measured by
      enzyme-linked immunosorbent assay and CXCR3(+) cells were counted by flow
      cytometry before treatment and at the period of improvement. RESULTS: There were
      no significant differences in visual acuity, intraocular pressure, and recurrence
      rate between the 2 groups. The mean time to improvement was 9.1 +/- 3.9 days in
      group A and 15.4 +/- 5.5 days in group B (P = 0.04). The concentrations of CXCL
      9, -10, and -11 were 562.7 +/- 109.4, 30293.1 +/- 12537.1, and 228.3 +/- 80.8
      pg/mL before treatment and 6.7 +/- 6.8 (P < 0.01), 207.5 +/- 209.8 (P < 0.01),
      and 18.9 +/- 19.5 (P < 0.01) pg/mL after treatment, respectively. The CXCL-10
      level correlated with the time to improvement of graft rejection (P = 0.02). Flow
      cytometry demonstrated a significantly decreased number of CXCR3(+) and
      CXCR3(+)CD4(+) cells in the aqueous humor after treatment. CONCLUSION: IVTA
      injection was effective in reducing the time to improvement of endothelial graft
      rejection. Increased expression of CXCL-9, -10, and -11, and their receptors in
      the aqueous humor of patients with endothelial graft rejection decreased after
      treatment.

PMID- 22367050
TI  - Pachymetry-guided intrastromal air injection ("pachy-bubble") for deep anterior
      lamellar keratoplasty.
AB  - To evaluate an innovative technique for intrastromal air injection to achieve
      deep anterior lamellar keratoplasty (DALK) with bare Descemet membrane (DM).
      Thirty-four eyes with anterior corneal pathology, including 27 with keratoconus,
      underwent DALK. After 400 MUm trephination with a suction trephine, ultrasound
      pachymetry was performed 0.8 mm internally from the trephination groove in the 11
      to 1 o'clock position. In this area, a 2-mm incision was created, parallel to the
      groove, with a micrometer diamond knife calibrated to 90% depth of the thinnest
      measurement. A cannula was inserted through the incision and 0.5 mL of air was
      injected to dissect the DM from the stroma. After peripheral paracentesis,
      anterior keratectomy was carried out to bare the DM. A 0.25-mm oversized graft
      was sutured in place. Overall, 94.1% of eyes achieved DALK. Bare DM was achieved
      in 30 eyes, and a pre-DM dissection was performed in 2 eyes. Air injection was
      successful in detaching the DM (achieving the big bubble) in 88.2% of the eyes.
      In keratoconus eyes, the rate was 88.9%. All cases but one required a single air
      injection to achieve DM detachment. Microperforations occurred in 5 cases: 3
      during manual layer-by-layer dissection after air injection failed to detach the
      DM, 1 during removal of the residual stroma after big-bubble formation, and 1
      during the diamond knife incision. Two cases (5.9%) were converted to penetrating
      keratoplasty because of macroperforations. The technique was reproducible, safe,
      and highly effective in promoting DALK with bare DM.

PMID- 22367051
TI  - Trends in atrial fibrillation ablation: have we maximized the current paradigms?
AB  - PURPOSE: The purpose of this study was to evaluate how atrial fibrillation (AF)
      ablation has evolved over time with regards to patient characteristics,
      procedural variables, complications, and outcomes. METHODS: We evaluated trends
      over time from 2003 to 2010 in clinical characteristics, procedural variables,
      complications, and Kaplan-Meier AF-free rates after the initial and final AF
      ablation in 1,125 patients undergoing 1,504 ablations. RESULTS: Evaluating trends
      from 2003 to 2010, we found that patients undergoing AF ablation became older (P
      < 0.0001), had higher CHADS(2) scores (P < 0.0001), and more coronary artery
      disease (P = 0.021), persistent AF (P < 0.0001), hypertension (P < 0.0001), and
      previous strokes/transient ischemic attacks (P = 0.005). Procedure times
      decreased from 256 +/- 49 to 122 +/- 28 min (P < 0.0005), fluoroscopy times
      decreased from 134 +/- 29 to 56 +/- 19 min (P < 0.0005), and major (P = 0.023),
      minor (P = 0.023), and total complications (P = 0.001) decreased over time. The
      learning curve to minimize complications was 6 years. For paroxysmal AF, initial
      ablation AF-free rates improved over time (P = 0.015) but improvement plateaued
      in recent years. For persistent AF, initial ablation AF-free rates trended toward
      improvement over time (P = 0.062) but also plateaued in recent years. For long
      standing persistent AF (P = 0.995), there was no outcome improvement after
      initial ablation over time. There was no trend for improved final outcomes
      (including repeat ablations) over time for paroxysmal, persistent, or long
      standing AF (P = 0.150 to P = 0.978). CONCLUSIONS: Despite decreased procedural
      and fluoroscopy times and reduced complication rates, post-ablation freedom from
      AF has not improved commensurately in recent years. A better understanding of AF
      initiation and maintenance may be required to devise personalized approaches to
      AF ablation and further improve outcomes.

PMID- 22367052
TI  - Aortic valve prosthesis selection in dialysis patients based on the patient's
      condition.
AB  - Previous studies have examined outcomes in dialysis patients undergoing cardiac
      surgery. However, only a few studies have solely focused on outcomes after aortic
      valve replacement (AVR). This study aimed to clarify independent predictors of
      the long-term survival of dialysis patients with AVR and to determine whether a
      mechanical valve or bioprosthesis is suitable based on the patient's condition. A
      total of 38 consecutive dialysis patients who underwent AVR at our institute were
      reviewed (mean age 69.1 +/- 9.4 years). There were 23 bioprostheses and 15
      mechanical valve replacements. The operative mortality and the long-term survival
      were not different between the bioprosthesis and the mechanical valve group (13.0
      vs. 13.3%). The significant multivariate predictors for long-term survival were
      concomitant coronary artery bypass grafting (CABG) and prosthesis size. Valve
      types and age at operation did not affect long-term survival. Five-year survival
      of patients with small prosthetic valves and concomitant CABG was 0%. When the
      patient's quality of life is taken into account, it may be appropriate to use a
      bioprosthesis in a dialysis patient with a small annulus and concomitant CABG
      even if the patient is young.

PMID- 22367053
TI  - Prevalence of spondylosis deformans in the feline spine and correlation with
      owner-perceived behavioural changes.
AB  - OBJECTIVES: The primary objective was to determine the prevalence, spinal
      distribution, and association with the signalment of cats suffering from
      different grades of feline spondylosis deformans (spondylosis). The secondary
      objective was to document behavioural changes associated with spondylosis by
      owner observation. METHODS: A cross-sectional study was performed to determine
      the prevalence of feline spondylosis (group 1). A prospective study was performed
      to determine the association between radiographic abnormalities of the
      lumbosacral region (L3-S1) and owner perceived behavioural changes based on a
      completed questionnaire (group 2). The radiographs were reviewed using a grading
      system (0-3) for spondylosis. RESULTS: The prevalence of spondylosis in group 1
      was 39.4% (158/402). Cats with spondylosis were significantly older than cats
      without spondylosis (p <0.001). The thoracic (T) vertebrae T4-T10 were most often
      affected by spondylosis, but spondylosis was most severe in the T10-S1 vertebrae.
      In group 2, spondylosis of the lumbosacral region was significantly correlated
      with owner-reported behavioural changes, such as a decreased willingness to greet
      people and to being petted, increased aggressiveness, and a poor perceived
      quality of life (p = 0.037). CLINICAL SIGNIFICANCE: This study found that feline
      spondylosis is common and that spondylosis of the lumbosacral region may be
      accompanied by behavioural changes.

PMID- 22367055
TI  - Emotional congruence in learning and health encounters in medicine: addressing an
      aspect of the hidden curriculum.
AB  - This paper aims to draw attention to and provide insights into an area that is of
      educational significance for clinical teachers, namely the need to acknowledge
      and respond appropriately to the emotional context of both learning and health
      encounters in order to improve the outcomes of both. This need has been
      highlighted by recent calls for more attention to be paid to the role of emotion
      within medical education and within health care provision. What is already known
      about the role of emotion in learner-teacher encounters and in patient-doctor
      encounters will be used to develop the concept of emotional congruence within
      these two types of encounter as a challenge to clinical teachers to examine their
      own practice. The reasons why emotional congruence is not always apparent in the
      learning environment of the teaching hospital will be discussed using the model
      of the 'hidden curriculum'. It will be suggested that explicit strategies to
      counteract the hidden curriculum in relation to emotion can bring about
      transformative change in individual practice and the health care environment that
      has the potential to improve both learning and health outcomes.

PMID- 22367054
TI  - Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic
      mice.
AB  - Transgenic mice expressing the diphtheria toxin receptor (DTR) in specific cell
      types are key tools for functional studies in several biological systems. B6.FVB
      Tg(Itgax-DTR/EGFP)57Lan/J (CD11c.DTR) and B6.Cg-Tg(Itgax-DTR/OVA/EGFP)1Gjh/Crl
      (CD11c.DOG) mice express the DTR in CD11c(+) cells, allowing conditional
      depletion of dendritic cells. We report that dendritic-cell depletion in these
      models caused polymorphonuclear neutrophil (PMN) release from the bone marrow,
      which caused chemokine-dependent neutrophilia after 6-24 h and increased
      bacterial clearance in a mouse pyelonephritis model. We present a transgenic
      mouse line, B6.Cg-Tg(Itgax-EGFP-CRE-DTR-LUC)2Gjh/Crl (CD11c.LuciDTR), which is
      unaffected by early neutrophilia. However, CD11c.LuciDTR and CD11c.DTR mice
      showed late neutrophilia 72 h after dendritic cell depletion, which was
      independent of PMN release and possibly resulted from increased granulopoiesis.
      Thus, the time point of dendritic cell depletion and the choice of DTR transgenic
      mouse line must be considered in experimental settings where neutrophils may be
      involved.

PMID- 22367056
TI  - Tocotrienol attenuates triglyceride accumulation in HepG2 cells and F344 rats.
AB  - Tocotrienol (T3) is an important phytonutrient found in rice bran and palm oil.
      T3 has gained much interest for lipid lowering effects, especially for
      cholesterol (Cho) by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
      Also, usefulness of T3 in improving triglyceride (TG) profiles has been
      suggested, but its efficacy and mechanism have been unclear. We investigated how
      T3 decreases TG concentration in cultured cells and animals. In a cell culture
      study, human hepatoma cells (HepG2) were incubated in a control or a fat (1 mM
      oleic acid)-loaded medium containing gamma-T3 for 24 h. We found that 10-15 MUM
      gamma-T3 inhibited cellular TG accumulation significantly, especially in the fat
      loaded medium. This manifestation was supported by mRNA and protein expressions
      of fatty acid synthase, carnitine palmitoyltransferase 1, and cytochrome P450
      3A4. In concordance with these results, rice bran T3 supplementation to F344 rats
      (5 or 10 mg T3/day/rat) receiving a high fat diet for 3 weeks significantly
      reduced TG and the oxidative stress marker (phospholipid hydroperoxides, PLOOH)
      in the liver and blood plasma. T3 supplementation did not show changes in the Cho
      level. These results provided new information and the mechanism of the TG
      lowering effect of T3. The lipid lowering effects of dietary T3 might be mediated
      by the reduction of TG synthesis.

PMID- 22367057
TI  - Influence of maternal diet during early pregnancy on the fatty acid profile in
      the fetus at late pregnancy in rats.
AB  - The aim of the study was to determine the effects of different dietary fatty
      acids during the first half of pregnancy on the fatty acid composition of
      maternal adipose tissue and of maternal and fetal plasma at mid- and late
      pregnancy. Pregnant rats received soybean-, olive-, fish-, linseed- or palm-oil
      diets from conception to day 12 of gestation. Virgin rats receiving the same
      treatments were studied in parallel. At day 12, some rats were sacrificed and
      others were returned to the standard diet and studied at day 20. At day 12, the
      concentrations of most fatty acids in plasma reflected the dietary composition
      and individual fatty acids in lumbar adipose tissue of pregnant rats correlated
      with those in the diet. At day 20, the plasma concentration of each fatty acid
      was higher in pregnant than in both virgin rats and day-12 pregnant rats. The
      composition in 20-day pregnant (but not in virgin) rats resembled the diet
      consumed during the first 12 days. Fatty acid concentration in fetal plasma was
      also influenced by the maternal diet during the first 12 days of pregnancy, and
      long-chain polyunsaturated fatty acid (LC-PUFA) concentrations correlated with
      those in the mothers. In conclusion, during the first half of pregnancy maternal
      adipose tissue stores dietary-derived fatty acids, which are released into blood
      during late pregnancy enabling LC-PUFA to become available to the fetus.

PMID- 22367059
TI  - Anatomical basis of the risk of injury to the right laryngeal recurrent nerve
      during thoracic surgery.
AB  - PURPOSE: Despite the intrathoracic part being short, the right laryngeal
      recurrent nerve is often injured during thoracic surgery. The aim of this cadaver
      study was to understand the mechanisms of right laryngeal recurrent nerve
      injuries during thoracic surgery and to describe anatomical landmarks for its
      preservation. METHODS: Dissections were performed on 10 fresh human cadavers. A
      right anterolateral thoracic wall segment was removed, preserving the first rib.
      Dissections were carried out to identify the following structures: first rib,
      esophagus, trachea, right main bronchus, right brachiocephalic and subclavian
      vessels, azygos vein, phrenic nerve, vagus nerve, and right laryngeal recurrent
      nerve. RESULTS: The distance between the origin of the right laryngeal recurrent
      nerve and its adjacent structures was assessed. Moderate traction of the thoracic
      part of the vagus nerve resulted in a downward translation of the right laryngeal
      recurrent nerve's origin. In such conditions, the right laryngeal recurrent
      nerve's origin was distant of 14.8 mm (+/-2.89 mm) from the subclavian artery.
      CONCLUSIONS: Intraoperative incidence of right laryngeal recurrent nerve direct
      injury could be decreased by understanding the detailed course of its
      intrathoracic part. Moreover, traction on the intrathoracic part of the right
      vagus nerve may result in indirect lesions of the right laryngeal recurrent
      nerve: stretch induced lesions and nerve vasculature's lesions.

PMID- 22367060
TI  - Analysis of functional status, quality of life and community integration in
      earthquake survivors with spinal cord injury at hospital discharge and one-year
      follow-up in the community.
AB  - OBJECTIVE: This study compares functional status, quality of life and community
      integration in 2008 Sichuan earthquake survivors with spinal cord injury at
      hospital discharge and at 1-year follow-up in the community. METHODS: Twenty-six
      subjects with spinal cord injury completed demographic and medical questionnaires
      and underwent medical examination at discharge from a hospital rehabilitation
      department and after 1 year in the community. Functional status, quality of life
      and community integration were assessed by appropriate instruments over this
      period. RESULTS: Functional status measures showed significantly increased (p <
      0.05) scores for the Modified Barthel Index and Walking Index for Spinal Cord
      Injury II; depression and pain scores were reduced with no statistical
      significance. After discharge, nearly half of patients developed a new pressure
      sore and most patients had urinary complications. Self-reported quality of life,
      overall health, and satisfaction with social relationships increased
      significantly (p < 0.05), while the environment domain was reduced (p < 0.05).
      Social participation (i.e. community integration) results showed an improvement
      in physical independence and mobility (p < 0.05), but a decline in cognitive
      independence (p < 0.05). Only 15% of the population returned to work. CONCLUSION:
      Special attention should be paid to cognitive and emotional function,
      occupational training and social integration during rehabilitation measures after
      earthquakes.

PMID- 22367061
TI  - Exchange chemistry of tBu3P(CO2)B(C6F5)2Cl.
AB  - Halide exchange from the species tBu(3)P(CO(2))B(C(6)F(5))(2)Cl 1 with
      Me(3)SiOSO(2)CF(3) gave tBu(3)P(CO(2))B(C(6)F(5))(2)(OSO(2)CF(3)) 2. Similarly,
      Lewis acid exchange occurs in reactions of 1 with Al(C(6)F(5))(3) and
      [Cp(2)TiMe][B(C(6)F(5))(4)] affording the products,
      tBu(3)P(CO(2))Al(C(6)F(5))(3)3 and [tBu(3)P(CO(2))TiCp(2)Cl][B(C(6)F(5))(4)] 4.

PMID- 22367062
TI  - Trehalose metabolism is activated upon chilling in grapevine and might
      participate in Burkholderia phytofirmans induced chilling tolerance.
AB  - During the last decade, there has been growing interest in the role of trehalose
      metabolism in tolerance to abiotic stress in higher plants, especially cold
      stress. So far, this metabolism has not yet been studied in Vitis vinifera L.,
      despite the economic importance of this crop. The goal of this paper was to
      investigate the involvement of trehalose metabolism in the response of grapevine
      to chilling stress, and to compare the response in plants bacterised with
      Burkholderia phytofirmans strain PsJN, a plant growth-promoting rhizobacterium
      that confers grapevine chilling tolerance, with mock-inoculated plants. In silico
      analysis revealed that the V. vinifera L. genome contains genes encoding the
      enzymes responsible for trehalose synthesis and degradation. Transcript analysis
      showed that these genes were differentially expressed in various plant organs,
      and we also characterised their response to chilling. Both trehalose and
      trehalose 6-phosphate (T6P) were present in grapevine tissues and showed a
      distinct pattern of accumulation upon chilling. Our results suggest a role for
      T6P as the main active molecule in the metabolism upon chilling, with a possible
      link with sucrose metabolism. Furthermore, plants colonised by B. phytofirmans
      and cultivated at 26 degrees C accumulated T6P and trehalose in stems and leaves
      at concentrations similar to non-bacterised plants exposed to chilling
      temperatures for 1 day. Overall, our data suggest that T6P and trehalose
      accumulate upon chilling stress in grapevine and might participate in the
      resistance to chilling stress conferred by B. phytofirmans.

PMID- 22367063
TI  - Hormonal changes during flower development in floral tissues of Lilium.
AB  - Much effort has been focussed on better understanding the key signals that
      modulate floral senescence. Although ethylene is one of the most important
      regulators of floral senescence in several species, Lilium flowers show low
      sensitivity to ethylene; thus their senescence may be regulated by other
      hormones. In this study we have examined how (1) endogenous levels of hormones in
      various floral tissues (outer and inner tepals, androecium and gynoecium) vary
      throughout flower development, (2) endogenous levels of hormones in such tissues
      change in cut versus intact flowers at anthesis, and (3) spray applications of
      abscisic acid and pyrabactin alter flower longevity. Results show that floral
      tissues behave differently in their hormonal changes during flower development.
      Cytokinin and auxin levels mostly increased in tepals prior to anthesis and
      decreased later during senescence. In contrast, levels of abscisic acid increased
      during senescence, but only in outer tepals and the gynoecium, and during the
      latest stages. In addition, cut flowers at anthesis differed from intact flowers
      in the levels of abscisic acid and auxins in outer tepals, salicylic acid in
      inner tepals, cytokinins, gibberellins and jasmonic acid in the androecium, and
      abscisic acid and salicylic acid in the gynoecium, thus showing a clear
      differential response between floral tissues. Furthermore, spray applications of
      abscisic acid and pyrabactin in combination accelerated the latest stages of
      tepal senescence, yet only when flower senescence was delayed with Promalin. It
      is concluded that (1) floral tissues differentially respond in their endogenous
      variations of hormones during flower development, (2) cut flowers have drastic
      changes in the hormonal balance not only of outer and inner tepals but also of
      androecium and gynoecium, and (3) abscisic acid may accelerate the progression of
      tepal senescence in Lilium.

PMID- 22367064
TI  - Do transcription factors hold the key to understanding the development of
      Barrett's esophagus?

PMID- 22367065
TI  - Innate immune reactivity of the ileum-liver axis in nonalcoholic steatohepatitis.
AB  - BACKGROUND: Over-proliferation and bacterial translocation of Gram-negative
      bacilli within the intestinal flora, and increased portal venous levels of
      endotoxins, are involved in nonalcoholic steatohepatitis (NASH). AIM: To evaluate
      the innate immune response in the small intestine and liver using the rat NASH
      model. METHODS: We produced the NASH model by administering a choline-deficient
      amino acid-defined diet to F344 rats. We analyzed the serum and liver tissue to
      assess the effects of innate immune reactivity in this NASH model. RESULTS:
      Significant increases were detected in serum ALT levels and in the portal venous
      serum and whole-liver levels of TNF-alpha and IFN-gamma in the NASH group. Strong
      Sirius red staining and TNF-alpha immune staining were seen in the NASH group,
      and real-time PCR revealed significantly increased expression of TNF-alpha and
      TLR4 mRNA in the NASH group. Higher TNF-alpha levels were detected in the Kupffer
      cells isolated culture supernatant in the NASH group than in the control group.
      Immune staining of the ileal tissue specimens resulted in greater staining of TNF
      alpha, TLR4, and macrophage/dendritic cells, mainly in the submucosa, in the NASH
      group than in the control group. CONCLUSIONS: In the small intestine and liver of
      the rat NASH model, the possibility that enhancement of the innate immune
      response, mediated by the TLR4 signal, led to increased production of TNF-alpha
      was suggested. This interaction between the small intestine and liver may be
      involved in the onset and progression of NASH.

PMID- 22367066
TI  - Role of autophagy in apoptosis induction by methylene chloride extracts of Mori
      cortex in NCI-H460 human lung carcinoma cells.
AB  - The root of Mori cortex has traditionally been used in Korea for the treatment of
      cutaneous inflammation, pulmonary asthma, and congestion for thousands of years.
      The present study was designed to validate the anticancer effects of methylene
      chloride extracts of the M. cortex root (MEMC) in NCI-H460 human lung carcinoma
      cells. Exposure to MEMC was found to result in growth inhibition by the induction
      of caspase-dependent apoptosis in NCI-H460 cells, which correlated with
      upregulated expression of death receptor (DR)4, DR5 and FasL, downregulation of
      anti-apoptotic Bcl-2 and Bcl-xL expression, cleavage of Bid, and loss of
      mitochondrial membrane potential. In addition, autophagosomes, a characteristic
      finding of autophagy, and markers of autophagy, conversion of microtubule
      associated protein light chain-3 (LC3)-I to LC3-II and increased beclin-1
      accumulation, were observed in MEMC-treated NCI-H460 cells. Inhibition of
      autophagy by 3-methyladenine or LC3B small interfering (siRNA) resulted in
      enhanced apoptotic cell death, suggesting that MEMC-induced autophagy functions
      as a suppressor of apoptosis. MEMC-induced autophagy was also blocked by N-acetyl
      cysteine (NAC) and catalase, indicating that H2O2 can regulate autophagy. Our
      data demonstrate that MEMC triggers both ROS-mediated autophagy and caspase
      dependent apoptosis, and that autophagy plays a protective role against apoptotic
      cell death.

PMID- 22367067
TI  - Reasons why women accept or reject the trivalent inactivated influenza vaccine
      (TIV) during pregnancy.
AB  - The aim of the study was to gain an in-depth understanding of the reasons why
      pregnant women accept or reject the seasonal influenza vaccine. The qualitative
      descriptive design used a face-to-face semi-structured interview format. Sixty
      pregnant and postpartum women at two hospitals in the Northeastern United States
      participated. Content analysis was the inductive method used to code the data and
      identify emergent themes. Six themes emerged from the data: differing degrees of
      influence affect action to vaccinate; two-for-one benefit is a pivotal piece of
      knowledge that influences future vaccination; fear if I do (vaccinate), fear if I
      don't; women who verbalize 'no need' for the vaccine also fear the vaccine; a
      conveniently located venue for vaccination reduces barriers to uptake; H1N1-a
      benefit and barrier to the seasonal vaccine. Our study supports previous findings
      and reveals a deeper understanding and interpretation of the behavior and
      decision-making to accept or reject the influenza vaccine. Understanding the
      reasons behind the behavior of vaccine rejection gives us the chance to change
      it.

PMID- 22367068
TI  - Compliance status of product labels to the international code on marketing of
      breast milk substitutes.
AB  - The aim of this study was to determine the compliance status of product labels
      regarding Article 9 of the International Code on Marketing of Breast-milk
      Substitutes (the Code) in Denizli province, Turkey. A cross-sectional study
      design was employed to determine the compliance status. The product labels were
      obtained from a convenience sample of five supermarkets, one store and 5
      pharmacies in the City centre and district of Honaz. Using a data collection form
      prepared by previously published studies, data were collected between July 26,
      2010 and August 06, 2010. Data collection form included 13 criteria. In addition,
      we checked the boxes for the availability of a Turkish written label. Forty
      product labels of 7 companies were reached and evaluated. These products
      consisted of 83.0% of the products marketed by these companies in Turkey. Thirty
      seven (92.5%) of the labels violated Article 9 of the Code in terms of one or
      more criteria. Thirty four (85.0%) of the labels had photos or pictures
      idealizing the use of infant formula. Nine (22.5%) had a photo, a picture or any
      representation of an infant, and five (12.5%) had text which idealize the use of
      infant formula or discouraging breastfeeding. Eight (20%) did not state that
      breastfeeding is the best. Four (10%) had a term such as 'similar to breast milk
      or human milk'. In conclusion, the majority of the product labels of breast milk
      substitutes marketed in our country violate the Code. It is appropriate that the
      Turkish Ministry of Health, medical organizations, companies, and NGOs work more
      actively to increase awareness of this issue.

PMID- 22367069
TI  - Production and processing studies on calpain-system gene markers for beef
      tenderness: consumer assessments of eating quality.
AB  - We investigated the effects of calpain-system genetic markers on consumer beef
      quality ratings, including interactions of marker effects with hormonal growth
      promotant (HGP) use and tenderstretch hanging. Brahman cattle in New South Wales
      (NSW; n = 164) and Western Australia (WA; n = 141) were selected at weaning from
      commercial and research herds to achieve balance and divergence in calpastatin
      (CAST) and calpain 3 (CAPN3) gene marker status. Genotypes for MU-calpain (CAPN1
      4751 and CAPN1-316) were also determined. Angus cattle (49 in NSW, 17 in WA) with
      favorable CAST and CAPN3 alleles, balanced for CAPN1-316 status, were also
      studied. Half the cattle at each site had HGP (Revalor-H, containing 200 mg
      trenbolone acetate and 20 mg 17beta-estradiol) implants during grain finishing.
      One side of each carcass was suspended from the Achilles tendon (AT) and the
      other from the pelvis [tenderstretch (TS)]. Meat Standards Australia consumer
      panels scored 7-d aged striploin steaks from both AT and TS sides, and 7-d aged
      rump and oyster blade steaks from the AT side of each carcass. Two favorable CAST
      alleles increased tenderness ratings of AT-striploin, TS-striploin, rump, and
      oyster blade steaks by, respectively, 6.1, 4.2, 4.2, and 3.1 units, and overall
      liking by 4.7, 2.8, 2.9, 3.7 (all P < 0.04). Two favorable CAPN1-4751 alleles
      increased tenderness of AT-striploin, TS-striploin, and rump steaks by 6.5, 4.3,
      and 3.9 units, and overall liking by 5.6, 3.1, and 4.1 units. Two favorable CAPN3
      alleles improved rump steaks by 3.7, 3.3, 3.7, and 3.5 units, for tenderness,
      juiciness, liking the flavor, and overall liking. There were no significant CAPN1
      316 effects. The effect of HGP was greatest for the AT-striploin (reducing
      tenderness and overall liking by 8.2 units, P < 0.001), then TS-striploin (-5.6
      for tenderness, -5.0 for overall liking, P < 0.001), and then rump (-4.4 for
      tenderness, -3.3 for overall liking, P < 0.007). Processing conditions differed
      considerably between NSW and WA. Rump steaks from NSW scored about 10 units
      greater than those from WA, but Angus and Brahman steaks from the same location
      with the same marker alleles had similar scores. In contrast, NSW Angus striploin
      steaks scored about 15 units greater for tenderness and overall liking (P <
      0.001) than cattle with the same marker alleles at the other 3 location * breed
      combinations, which had generally similar scores. Therefore, calpain-system gene
      markers have beneficial effects on eating quality, consistent with our previous
      findings for objective meat quality.

PMID- 22367070
TI  - Is sperm DNA fragmentation a good marker for field AI bull fertility?
AB  - This paper aimed at investigating the potential use of sperm DNA fragmentation
      (SDF) to improve the routine screening of infertility of Holstein bulls.
      Cryopreserved sperm samples from 201 Holstein bulls provided by an AI center were
      used in the analyses of SDF at 0 (SDF_0) and 6 (SDF_6) h of incubation at 37
      degrees C. A refinement of the sperm chromatin dispersion test implemented in the
      Sperm-Halomax kit was employed to measure SDF. Records on routinely collected
      semen traits (volume, concentration, mass and individual motility evaluated in
      the fresh ejaculate, and individual motility in post-thawed semen straws) were
      provided by the AI center. Artificial insemination bull fertility was obtained
      from official field recording as successful or failed insemination. The results
      show that the average SDF was low (around 3.5%) at 0 and 6 h of incubation. A
      moderate effect of inbreeding depression was found. Estimated heritability for
      SDF traits were moderately high (0.41 and 0.29 for SDF_0 and SDF_6, respectively)
      and estimated repeatability of SDF measures in the same animal were high (0.73
      and 0.70 for SDF_0 and SDF_6, respectively). An overall estimated service bull
      value (ESBV) obtained through statistical modeling that allowed for adjustment of
      systematic environmental effects not specific to a bull and of the female
      contribution to fertility, and the estimated genetic values (EGV) were obtained
      from field-recorded AI information. The ESBV and EGV were also obtained for all
      semen traits. Moderately large and negative Pearson correlation coefficients were
      observed between SDF traits and male fertility ranging from (-0.43 to -0.50; P
      <0.001). Results of stepwise regression analyses showed that SDF_6 had the
      largest partial r(2) (0.15 to 0.26) among all semen characteristics. Overall, the
      selected semen traits explained 25% and 31% of the observed variability in bull
      fertility measured as EGV and ESBV, respectively. When looking at the predictive
      ability of bull fertility categories, the results of discriminant and logistic
      regression analyses showed that low-fertility bulls (those in the 10th or lower
      percentile in the fertility distribution) can be accurately identified by using
      measures of SDF alone or in combination with sperm motility. Values of SDF around
      7% to 10% could be used as indicators of low AI success.

PMID- 22367071
TI  - Mannan oligosaccharide increases serum concentrations of antibodies and
      inflammatory mediators in weanling pigs experimentally infected with porcine
      reproductive and respiratory syndrome virus.
AB  - Mannan-containing products are capable of modulating immune responses in animals.
      However, different products may have diverse immunomodulation. The experiment was
      conducted to examine effects of mannan oligosaccharide (Actigen; ACT) on growth
      performance and serum concentrations of antibodies and inflammatory mediators in
      weanling pigs (Sus scrofa) experimentally infected with porcine reproductive and
      respiratory syndrome virus (PRRSV). A total of 32 PRRSV-negative pigs (3 wk old)
      were randomly assigned from within blocks to 1 of 4 treatments in a 2 by 2
      factorial arrangement [2 types of diet: control (0%) and ACT addition (0.04%);
      and with and without PRRSV] in a randomized complete block design. Pigs were
      blocked by initial BW within sex. Ancestry was equalized across treatments. Pigs
      (8/treatment) were kept individually in each pen. After 2 wk of an 8-wk period of
      feeding the treatments, pigs received an intranasal inoculation of PRRSV or sham
      medium at 5 wk of age. Infection by PRRSV decreased ADG, ADFI, and G:F throughout
      the experiment (P < 0.01). Actigen did not affect ADG (P = 0.450), but decreased
      (P = 0.047) ADFI from 28 to 42 days postinoculation (DPI). During that time, ACT
      improved G:F in infected pigs but not in sham controls (interaction, P = 0.009).
      Dietary ACT did not affect viremia in infected pigs (P > 0.05), but increased
      PRRSV-specific antibody titer at 35 DPI (P = 0.042). Infection with PRRSV induced
      the febrile responses of pigs from 3 to 10 DPI (P < 0.001) with return to normal
      at 14 DPI. During the experimental period, the rectal temperature of pigs was
      found slightly elevated by ACT (P = 0.045). Infected pigs had greater serum
      concentrations of IL-1beta, tumor necrosis factor (TNF)-alpha, IL-12, interferon
      (IFN)-gamma, IL-10, and haptoglobin (Hp) than sham controls (P < 0.001). These
      results indicate that PRRSV stimulated secretion of cytokines involved in innate,
      T-helper 1, and T-regulatory immune responses. Actigen tended to decrease the
      serum TNF-alpha concentration regardless of PRRSV (P = 0.058). The ACT * PRRSV
      interaction was significant for IL-1beta (P = 0.016), IL-12 (P = 0.026), and Hp
      (P = 0.047), suggesting that infected pigs fed ACT had greater serum
      concentrations of these mediators than those fed the control. The increases in IL
      1beta and IL-12 may favorably promote innate and T-cell immune functions in
      infected pigs fed ACT. Feeding ACT may be useful as ACT is related to increased
      PRRSV antibody titers and G:F in infected pigs at certain times during infection.

PMID- 22367072
TI  - Effects of cooked navy bean powder on apparent total tract nutrient digestibility
      and safety in healthy adult dogs.
AB  - Dry beans (Phaseolus vulgaris L., Fabaceae) are a low glycemic index food
      containing protein, fiber, minerals, essential vitamins, and bioactive compounds
      and have not been evaluated for inclusion in commercial canine diets. The
      objective of this study was to establish the apparent total tract digestibility
      and safety of cooked navy bean powder when incorporated into a canine diet
      formulation at 25% (wt/wt) compared with a macro- and micro-nutrient matched
      control. Twenty-one healthy, free-living, male and female adult dogs of different
      breeds were used in a randomized, blinded, placebo controlled, 28-d dietary
      intervention study. Apparent total tract energy and nutrient digestibility of the
      navy bean powder diet were compared with the control diet. Digestibilities and ME
      content were 68.58 and 68.89% DM, 78.22 and 79.49% CP, 77.57 and 74.91% OM, 94.49
      and 93.85% acid hydrolyzed fat, and 3,313 and 3,195 kcal ME/kg for the navy bean
      diet and control diet, respectively. No differences were observed between the
      groups. No increased flatulence or major change in fecal consistency was
      observed. Navy bean powder at 25% (wt/wt) of total diet was determined to be
      palatable (on the basis of intake and observation) and digestible in a variety of
      dog breeds. No changes were detected in clinical laboratory values, including
      complete blood counts, blood biochemical profiles, and urinalysis in either the
      bean or control diet groups. These results indicate that cooked navy bean powder
      can be safely included as a major food ingredient in canine diet formulations and
      provide a novel quality protein source, and its use warrants further
      investigation as a functional food for chronic disease control and prevention.

PMID- 22367073
TI  - Direct fed microbial supplementation repartitions host energy to the immune
      system.
AB  - Direct fed microbials and probiotics are used to promote health in livestock and
      poultry; however, their mechanism of action is still poorly understood. We
      previously reported that direct fed microbial supplementation in young broilers
      reduced ileal respiration without changing whole-body energy expenditure. The
      current studies were conducted to further investigate the effects of a direct fed
      microbial on energy metabolism in different tissues of broilers. One hundred
      ninety-two 1-d-old broiler chicks (16 chicks/pen) were randomly assigned to 2
      dietary groups: standard control starter diet (CSD) and CSD plus direct fed
      microbial (DFMD; 0.3%) with 6 pens/treatment. Body weight, feed consumption,
      whole-body energy expenditure, organ mass, tissue respiration rates, and
      peripheral blood mononuclear cell (PBMC) ATP concentrations were measured to
      estimate changes in energy metabolism. No differences in whole body energy
      expenditure or BW gain were observed; however, decreased ileal O(2) respiration
      (P < 0.05) was measured in DFMD fed broilers. In contrast, the respiration rate
      of the thymus in those broilers was increased (P < 0.05). The PBMC from DFMD fed
      broilers had increased ATP concentrations and exhibited increased ATP turnover (P
      < 0.01). To determine if the increased energy consumption by PBMC corresponded
      with an altered immune response, broilers were immunized with sheep red blood
      cells (SRBC) and assayed for differences in their humoral response. The DFMD-fed
      broilers had a faster rate of antigen specific IgG production (P < 0.05) and an
      increase in total IgA (P < 0.05). Collectively, these data indicate that
      supplementation with the direct fed microbial used in this study resulted in
      energy re-partitioning to the immune system and an increase in antibody
      production independent of changes in whole body metabolism or growth performance.

PMID- 22367074
TI  - Identification and association analysis of several hundred single nucleotide
      polymorphisms within candidate genes for back fat thickness in Italian Large
      White pigs using a selective genotyping approach.
AB  - Combining different approaches (resequencing of portions of 54 obesity candidate
      genes, literature mining for pig markers associated with fat deposition or
      related traits in 77 genes, and in silico mining of porcine expressed sequence
      tags and other sequences available in databases), we identified and analyzed 736
      SNP within candidate genes to identify markers associated with back fat thickness
      (BFT) in Italian Large White sows. Animals were chosen using a selective
      genotyping approach according to their EBV for BFT (276 with most negative and
      279 with most positive EBV) within a population of ~ 12,000 pigs. Association
      analysis between the SNP and BFT has been carried out using the MAX test proposed
      for case-control studies. The designed assays were successful for 656 SNP: 370
      were excluded (low call rate or minor allele frequency <5%), whereas the
      remaining 286 in 212 genes were taken for subsequent analyses, among which 64
      showed a P(nominal) value <0.1. To deal with the multiple testing problem in a
      candidate gene approach, we applied the proportion of false positives (PFP)
      method. Thirty-eight SNP were significant (P(PFP) < 0.20). The most significant
      SNP was the IGF2 intron3-g.3072G>A polymorphism (P(nominal) < 1.0E-50). The
      second most significant SNP was the MC4R c.1426A>G polymorphism (P(nominal) =
      8.0E-05). The third top SNP (P(nominal) = 6.2E-04) was the intronic TBC1D1
      g.219G>A polymorphic site, in agreement with our previous results obtained in an
      independent study. The list of significant markers also included SNP in
      additional genes (ABHD16A, ABHD5, ACP2, ALMS1, APOA2, ATP1A2, CALR, COL14A1,
      CTSF, DARS, DECR1, ENPP1, ESR1, GH1, GHRL, GNMT, IKBKB, JAK3, MTTP, NFKBIA, NT5E,
      PLAT, PPARG, PPP2R5D, PRLR, RRAGD, RFC2, SDHD, SERPINF1, UBE2H, VCAM1, and WAT).
      Functional relationships between genes were obtained using the Ingenuity Pathway
      Analysis (IPA) Knowledge Base. The top scoring pathway included 19 genes with a
      P(nominal) < 0.1, 2 of which (IKBKB and NFKBIA) are involved in the hypothalamic
      IKKbeta/NFkappaB program that could represent a key axis to affect fat deposition
      traits in pigs. These results represent a starting point to plan marker-assisted
      selection in Italian Large White nuclei for BFT. Because of similarities between
      humans and pigs, this study might also provide useful clues to investigate
      genetic factors affecting human obesity.

PMID- 22367075
TI  - Direct and associative effects for androstenone and genetic correlations with
      backfat and growth in entire male pigs.
AB  - In the pig industry, male piglets are surgically castrated early in life to
      prevent boar taint. Boar taint is mainly caused by androstenone and skatole.
      Androstenone is a pheromone that can be released from the salivary glands when
      the boar is sexually aroused. Boars are housed in groups and as a consequence
      boars can influence and be influenced by the phenotype of other boars by (non
      )heritable social interactions. The influence of these social interactions on
      androstenone is not well understood. The objective of this study is to
      investigate whether androstenone concentrations are affected by (non-)heritable
      social interactions and estimate their genetic correlation with growth rate and
      backfat. The dataset contained 6,245 boars, of which 4,455 had androstenone
      observations (68%). The average number of animals per pen was 7 and boars were
      housed in 899 unique pen-groups (boars within a single pen) and 344 unique
      compartment-groups (boars within a unique 'room' within a barn during time). Four
      models including different random effects, were compared for androstenone. Direct
      genetic, associative (also known as social genetic or indirect genetic effects),
      group, compartment, common environment and residual effects were included as
      random effects in the full model (M3). Including random pen and compartment
      effects (non-heritable social effects) significantly improved the model (M2)
      compared with including only direct, common environment and residual as random
      effects (M1, P < 0.001), and including associative effects even more (M3, P <
      0.001). The sum of the direct and associative variance components determines the
      total genetic variance of the trait. The associative effect explained 11.7% of
      the total genetic variance. Backfat thickness was analysed using M2 and growth
      using M3. The genetic correlation between backfat (direct genetic variance) and
      total genetic variance for androstenone was close to 0. Backfat and the direct
      and associative effects for androstenone had genetic correlations of 0.14 +/-
      0.08 and -0.25 +/- 0.18, respectively. The genetic correlation between total
      genetic variances for growth rate and androstenone was 0.33 +/- 0.18. The genetic
      correlation between direct effects was 0.11 +/- 0.09 and between associative
      effects was 0.42 +/- 0.31. The genetic correlations and current selection towards
      lower backfat and greater growth rate suggest that no major change in
      androstenone is expected when breeding goals are not changed. For selection
      against boar taint and therefore also against androstenone , results recommend
      that at least the social environment of the boars should be considered.

PMID- 22367076
TI  - Suppression of twins in b-oriented MFI molecular sieve films under microwave
      irradiation.
AB  - Twin growth in the synthesis of b-oriented MFI films is successfully suppressed
      by applying microwave irradiation on a b-oriented MFI seed layer, relying on the
      nucleation-related bottleneck effect. Electrochemical oxidation experiments
      demonstrated the importance of twin suppression in enhancing the diffusion of
      guest molecules in MFI films.

PMID- 22367077
TI  - Variation in stress resistance patterns among stx genotypes and genetic lineages
      of shiga toxin-producing Escherichia coli O157.
AB  - To evaluate the relationship between bacterial genotypes and stress resistance
      patterns, we exposed 57 strains of Shiga toxin-producing Escherichia coli (STEC)
      O157 to acid, freeze-thaw, heat, osmotic, oxidative, and starvation stresses.
      Inactivation rates were calculated in each assay and subjected to univariate and
      multivariate analyses, including principal component analysis (PCA) and cluster
      analysis. The stx genotype was determined for each strain as was the lineage
      specific polymorphism assay (LSPA6) genotype. In univariate analyses, strains of
      the stx(1) stx(2) genotype showed greater resistance to heat than strains of the
      stx(1) stx(2c) genotype; moreover, strains of the stx(1) stx(2) genotype showed
      greater resistance to starvation than strains of the stx(2) or stx(2c) genotypes.
      LSPA6 lineage I (LI) strains showed greater resistance to heat and starvation
      than LSPA6 lineage II (LII) strains. PCA revealed a general trend that a strain
      with greater resistance to one type of stress tended to have greater resistance
      to other types of stresses. In cluster analysis, STEC O157 strains were grouped
      into stress-resistant, stress-sensitive, and intermediate clusters. In stx
      genotypes, all strains of the stx(1) stx(2) genotype were grouped with the stress
      resistant cluster, whereas 72.7% (8/11) of strains of the stx(1) stx(2c) genotype
      grouped with the stress-sensitive cluster. In LI strains, 77.8% (14/18) of the
      strains were grouped with the stress-resistant cluster, whereas 64.7% (11/17) of
      LII strains were grouped with the stress-sensitive cluster. These results
      indicate that the genotypes of STEC O157 that are frequently associated with
      human illness, i.e., LI or the stx(1) stx(2) genotype, have greater multiple
      stress resistance than do strains of other genotypes.

PMID- 22367078
TI  - Characterization of bioaerosols from dairy barns: reconstructing the puzzle of
      occupational respiratory diseases by using molecular approaches.
AB  - To understand the etiology of exposure-related diseases and to establish
      standards for reducing the risks associated with working in contaminated
      environments, the exact nature of the bioaerosol components must be defined.
      Molecular biology tools were used to evaluate airborne bacterial and, for the
      first time, archaeal content of dairy barns. Three air samplers were tested in
      each of the 13 barns sampled. Up to 10(6) archaeal and 10(8) bacterial 16S rRNA
      genes per m(3) of air were detected. Archaeal methanogens, mainly
      Methanobrevibacter species, were represented. Saccharopolyspora rectivirgula, the
      causative agent of farmer's lung, was quantified to up to 10(7) 16S rRNA genes
      per m(3) of air. In addition, a wide variety of bacterial agents were present in
      our air samples within the high airborne bioaerosol concentration range. Despite
      recommendations regarding hay preservation and baling conditions, farmers still
      develop an S. rectivirgula-specific humoral immune response, suggesting intense
      and continuous exposure. Our results demonstrate the complexity of bioaerosol
      components in dairy barns which could play a role in occupational respiratory
      diseases.

PMID- 22367079
TI  - Concentration of norovirus during wastewater treatment and its impact on oyster
      contamination.
AB  - The concentrations of Escherichia coli, F-specific RNA bacteriophage (FRNA
      bacteriophage), and norovirus genogroup I (NoV GI) and norovirus genogroup II
      (NoV GII) in wastewater were monitored weekly over a 1-year period at a
      wastewater treatment plant (WWTP) providing secondary wastewater treatment. A
      total of 49 samples of influent wastewater and wastewater that had been treated
      by primary and secondary wastewater treatment processes (primary and secondary
      treated wastewater) were analyzed. Using a real-time reverse transcription
      quantitative PCR (RT-qPCR), the mean NoV GI and NoV GII concentrations detected
      in effluent wastewater were 2.53 and 2.63 log(10) virus genome copies 100 ml(-1),
      respectively. The mean NoV concentrations in wastewater during the winter period
      (January to March) (n = 12) were 0.82 (NoV GI) and 1.41 (NoV GII) log units
      greater than the mean concentrations for the rest of the year (n = 37). The mean
      reductions of NoV GI and GII during treatment were 0.80 and 0.92 log units,
      respectively, with no significant difference detected in the extent of NoV
      reductions due to season. No seasonal trend was detected in the concentrations of
      E. coli or FRNA bacteriophage in wastewater influent and showed mean reductions
      of 1.49 and 2.13 log units, respectively. Mean concentrations of 3.56 and 3.72
      log(10) virus genome copies 100 ml(-1) for NoV GI and GII, respectively, were
      detected in oysters sampled adjacent to the WWTP discharge. A strong seasonal
      trend was observed, and the concentrations of NoV GI and GII detected in oysters
      were correlated with concentrations detected in the wastewater effluent. No
      seasonal difference was detected in concentrations of E. coli or FRNA
      bacteriophage detected in oysters.

PMID- 22367080
TI  - Moraxella species are primarily responsible for generating malodor in laundry.
AB  - Many people in Japan often detect an unpleasant odor generated from laundry that
      is hung to dry indoors or when using their already-dried laundry. Such an odor is
      often described as a "wet-and-dirty-dustcloth-like malodor" or an "acidic or
      sweaty odor." In this study, we isolated the major microorganisms associated with
      such a malodor, the major component of which has been identified as 4-methyl-3
      hexenoic acid (4M3H). The isolates were identified as Moraxella osloensis by
      morphological observation and biochemical and phylogenetic tree analyses. M.
      osloensis has the potential to generate 4M3H in laundry. The bacterium is known
      to cause opportunistic infections but has never been known to generate a malodor
      in clothes. We found that M. osloensis exists at a high frequency in various
      living environments, particularly in laundry in Japan. The bacterium showed a
      high tolerance to desiccation and UV light irradiation, providing one of the
      possible reasons why they survive in laundry during and even after drying.

PMID- 22367081
TI  - Growth of aerobic ripening bacteria at the cheese surface is limited by the
      availability of iron.
AB  - The microflora on the surface of smear-ripened cheeses is composed of various
      species of bacteria and yeasts that contribute to the production of the desired
      organoleptic properties. The objective of the present study was to show that iron
      availability is a limiting factor in the growth of typical aerobic ripening
      bacteria in cheese. For that purpose, we investigated the effect of iron or
      siderophore addition in model cheeses that were coinoculated with a yeast and a
      ripening bacterium. Both iron and the siderophore desferrioxamine B stimulated
      the growth of ripening bacteria belonging to the genera Arthrobacter,
      Corynebacterium, and Brevibacterium. The extent of stimulation was strain
      dependent, and generally, the effect of desferrioxamine B was greater than that
      of iron. Measurements of the expression of genes related to the metabolism of
      iron by Arthrobacter arilaitensis Re117 by real-time reverse transcription-PCR
      showed that these genes were transcribed during growth in cheese. The addition of
      desferrioxamine B increased the expression of two genes encoding iron-siderophore
      ABC transport binding proteins. The addition of iron decreased the expression of
      siderophore biosynthesis genes and of part of the genes encoding iron-siderophore
      ABC transport components. It was concluded that iron availability is a limiting
      factor in the growth of typical cheese surface bacteria. The selection of strains
      with efficient iron acquisition systems may be useful for the development of
      defined-strain surface cultures. Furthermore, the importance of iron metabolism
      in the microbial ecology of cheeses should be investigated since it may result in
      positive or negative microbial interactions.

PMID- 22367082
TI  - Isolation of a Paenibacillus sp. strain and structural elucidation of its broad
      spectrum lipopeptide antibiotic.
AB  - This research was initiated to search for novel antimicrobial compounds produced
      by food or environmental microorganisms. A new bacterial strain, designated OSY
      SE, which produces a unique and potent antimicrobial agent was isolated from
      soil. The isolate was identified as a Paenibacillus sp. through cultural,
      biochemical, and genetic analyses. An antimicrobial compound was extracted from
      Paenibacillus OSY-SE with acetonitrile and purified using liquid chromatography.
      After analyses by mass spectrometry (MS) and nuclear magnetic resonance (NMR),
      the antimicrobial compound was determined to be a cyclic lipopeptide consisting
      of a C(15) fatty acyl (FA) chain and 13 amino acids. The deduced sequence is FA
      Orn-Val-Thr-Orn-Ser-Val-Lys-Ser-Ile-Pro-Val-Lys-Ile. The carboxyl-terminal Ile is
      connected to Thr by ester linkage. The new compound, designated paenibacterin,
      showed antagonistic activities against most Gram-positive and Gram-negative
      bacteria tested, including Listeria monocytogenes, methicillin-resistant
      Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella enterica serovar
      Typhimurium. Paenibacterin is resistant to trypsin, lipase, alpha-glucosidase,
      and lysozyme. Its antimicrobial activity was lost after digestion by pronase and
      polymyxin acylase. Paenibacterin is readily soluble in water and fairly stable to
      exposure to heat and a wide range of pH values. The new isolate and its
      antimicrobial agent are being investigated for usefulness in food and medical
      applications.

PMID- 22367084
TI  - Microbial scout hypothesis and microbial discovery.
AB  - In this study, we examine the temporal pattern of colony appearance during
      cultivation experiments, and whether this pattern could inform on optimizing the
      process of microbial discovery. In a series of long-term cultivation experiments,
      we observed an expected gradual increase over time of the total number of
      microbial isolates, culminating in a 700-fold colony count increase at 18 months.
      Conventional thought suggests that long-term incubations result in a culture
      collection enriched with species that are slow growing or rare, may be
      unavailable from short-term experiments, and likely are novel. However, after we
      examined the phylogenetic novelty of the isolates as a function of the time of
      their isolation, we found no correlation between the two. The probability of
      discovering either a new or rare species late in the incubation matched that of
      species isolated earlier. These outcomes are especially notable because of their
      generality: observations were essentially identical for marine and soil bacteria
      as well as for spore formers and non-spore formers. These findings are consistent
      with the idea of the stochastic awakening of dormant cells, thus lending support
      to the scout model. The process of microbial discovery is central to the study of
      environmental microorganisms and the human microbiome. While long-term incubation
      does not appear to increase the probability of discovering novel species, the
      technology enabling such incubations, i.e., single-cell cultivation, may still be
      the method of choice. While it does not necessarily allow more species to grow
      from a given inoculum, it minimizes the overall isolation effort and supplies
      needed.

PMID- 22367083
TI  - Microbial scout hypothesis, stochastic exit from dormancy, and the nature of slow
      growers.
AB  - We recently proposed a scout model of the microbial life cycle (S. S. Epstein,
      Nature 457:1083, 2009), the central element of which is the hypothesis that
      dormant microbial cells wake up into active (so-called scout) cells
      stochastically, independently of environmental cues. Here, we check the principal
      prediction of this hypothesis: under growth-permissive conditions, dormant cells
      initiate growth at random time intervals and exhibit no species-specific lag
      phase. We show that a range of microorganisms, including environmental species,
      Escherichia coli, and Mycobacterium smegmatis, indeed wake up in a seemingly
      stochastic manner and independently of environmental conditions, even in the
      longest incubations conducted (months to years long). As is implicit in the
      model, most of the cultures we obtained after long incubations were not
      inherently slow growers. Of the environmental isolates that required >=7 months
      to form visible growth, only 5% needed an equally long incubation upon
      subculturing, with the majority exhibiting regrowth within 24 to 48 h. This
      apparent change was not a result of adaptive mutation; rather, most microbial
      species that appear to be slow growers were in fact fast growers with a delayed
      initiation of division. Genuine slow growth thus appears to be less significant
      than previously believed. Random, low-frequency exit from the nongrowing state
      may be a key element of a general microbial survival strategy, and the
      phylogenetic breadth of the organisms exhibiting such exit indicates that it
      represents a general phenomenon. The stochasticity of awakening can also provide
      a parsimonious explanation to several microbiological observations, including the
      apparent randomness of latent infections and the existence of viable-but
      nonculturable cells (VBNC).

PMID- 22367085
TI  - Efficacy of biocides used in the modern food industry to control salmonella
      enterica, and links between biocide tolerance and resistance to clinically
      relevant antimicrobial compounds.
AB  - Biocides play an essential role in limiting the spread of infectious disease. The
      food industry is dependent on these agents, and their increasing use is a matter
      for concern. Specifically, the emergence of bacteria demonstrating increased
      tolerance to biocides, coupled with the potential for the development of a
      phenotype of cross-resistance to clinically important antimicrobial compounds,
      needs to be assessed. In this study, we investigated the tolerance of a
      collection of susceptible and multidrug-resistant (MDR) Salmonella enterica
      strains to a panel of seven commercially available food-grade biocide
      formulations. We explored their abilities to adapt to these formulations and
      their active biocidal agents, i.e., triclosan, chlorhexidine, hydrogen peroxide,
      and benzalkonium chloride, after sequential rounds of in vitro selection.
      Finally, cross-tolerance of different categories of biocidal formulations, their
      active agents, and the potential for coselection of resistance to clinically
      important antibiotics were investigated. Six of seven food-grade biocide
      formulations were bactericidal at their recommended working concentrations. All
      showed a reduced activity against both surface-dried and biofilm cultures. A
      stable phenotype of tolerance to biocide formulations could not be selected. Upon
      exposure of Salmonella strains to an active biocidal compound, a high-level of
      tolerance was selected for a number of Salmonella serotypes. No cross-tolerance
      to the different biocidal agents or food-grade biocide formulations was observed.
      Most tolerant isolates displayed changes in their patterns of susceptibility to
      antimicrobial compounds. Food industry biocides are effective against planktonic
      Salmonella. When exposed to sublethal concentrations of individual active
      biocidal agents, tolerant isolates may emerge. This emergence was associated with
      changes in antimicrobial susceptibilities.

PMID- 22367086
TI  - Fusion of a novel genetically engineered chitosan affinity protein and green
      fluorescent protein for specific detection of chitosan in vitro and in situ.
AB  - Chitin is the second most abundant polysaccharide, present, e.g., in insect and
      arthropod exoskeletons and fungal cell walls. In some species or under specific
      conditions, chitin appears to be enzymatically de-N-acetylated to chitosan-e.g.,
      when pathogenic fungi invade their host tissues. Here, the deacetylation of
      chitin is assumed to represent a pathogenicity mechanism protecting the fungus
      from the host's chitin-driven immune response. While highly specific chitin
      binding lectins are well known and easily available, this is not the case for
      chitosan-specific probes. This is partly due to the poor antigenicity of chitosan
      so that producing high-affinity, specific antibodies is difficult. Also, lectins
      with specificity to chitosan have been described but are not commercially
      available, and our attempts to reproduce the findings were not successful. We
      have, therefore, generated a fusion protein between a chitosanase inactivated by
      site-directed mutagenesis, the green fluorescent protein (GFP), and StrepII, as
      well as His(6) tags for purification and detection. The recombinant chitosan
      affinity protein (CAP) expressed in Escherichia coli was shown to specifically
      bind to chitosan, but not to chitin, and the affinity increased with decreasing
      degree of acetylation. In vitro, CAP detection was possible either based on GFP
      fluorescence or using Strep-Tactin conjugates or anti-His(5) antibodies. CAP
      fluorescence microscopy revealed binding to the chitosan exposing endophytic
      infection structures of the wheat stem rust fungus, but not the chitin exposing
      ectophytic infection structures, verifying its suitability for in situ chitosan
      staining.

PMID- 22367087
TI  - Biodegradation of trichloroethylene by an endophyte of hybrid poplar.
AB  - We isolated and characterized a novel endophyte from hybrid poplar. This unique
      endophyte, identified as Enterobacter sp. strain PDN3, showed high tolerance to
      trichloroethylene (TCE). Without the addition of inducers, such as toluene or
      phenol, PDN3 rapidly reduced TCE levels in medium from 72.4 MUM to 30.1 MUM in 24
      h with a concurrent release of 127 MUM chloride ion, and nearly 80% of TCE (55.3
      MUM) was dechlorinated by PDN3 in 5 days with 166 MUM chloride ion production,
      suggesting TCE degradation.

PMID- 22367088
TI  - Genome scanning for conditionally essential genes in Salmonella enterica Serotype
      Typhimurium.
AB  - As more whole-genome sequences become available, there is an increasing demand
      for high-throughput methods that link genes to phenotypes, facilitating discovery
      of new gene functions. In this study, we describe a new version of the Tn-seq
      method involving a modified EZ:Tn5 transposon for genome-wide and quantitative
      mapping of all insertions in a complex mutant library utilizing massively
      parallel Illumina sequencing. This Tn-seq method was applied to a genome
      saturating Salmonella enterica serotype Typhimurium mutant library recovered from
      selection under 3 different in vitro growth conditions (diluted Luria-Bertani
      [LB] medium, LB medium plus bile acid, and LB medium at 42 degrees C), mimicking
      some aspects of host stressors. We identified an overlapping set of 105 protein
      coding genes in S. Typhimurium that are conditionally essential under at least
      one of the above selective conditions. Competition assays using 4 deletion
      mutants (pyrD, glnL, recD, and STM14_5307) confirmed the phenotypes predicted by
      Tn-seq data, validating the utility of this approach in discovering new gene
      functions. With continuously increasing sequencing capacity of next generation
      sequencing technologies, this robust Tn-seq method will aid in revealing
      unexplored genetic determinants and the underlying mechanisms of various
      biological processes in Salmonella and the other approximately 70 bacterial
      species for which EZ:Tn5 mutagenesis has been established.

PMID- 22367089
TI  - Purification and characterization of a novel subtype a3 botulinum neurotoxin.
AB  - Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of
      considerable importance due to their being the cause of human and animal
      botulism, their potential as bioterrorism agents, and their utility as important
      pharmaceuticals. Type A is prominent due to its high toxicity and long duration
      of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2,
      and -/A5 have been purified, and their properties have been studied. BoNT/A3 is
      intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1
      antibodies, and thus, it may potentially replace BoNT/A1 for patients who have
      become refractive to treatment with BoNT/A1 due to antibody formation or other
      modes of resistance. Purification of BoNT/A3 has been challenging because of its
      low levels of production in culture and the need for innovative purification
      procedures. In this study, modified Mueller-Miller medium was used in place of
      traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain)
      and boost toxin production. BoNT/A3 titers were at least 10-fold higher than
      those produced in TPM. A purification method was developed to obtain greater than
      95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse
      bioassay was 5.8 * 10(7) 50% lethal doses (LD(50))/mg. Neutralization of BoNT/A3
      toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less
      than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms
      were observed between mice that were injected with BoNT/A3 and those that were
      injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical
      and pharmacological properties compared to those of other subtype A toxins.

PMID- 22367090
TI  - Decreased expression of repulsive guidance molecule member A by DNA methylation
      in colorectal cancer is related to tumor progression.
AB  - Previous studies have shown decreased expression of repulsive guidance molecule
      member A (RGMa) in colorectal cancer. However, the relationship between the
      expression levels and promoter DNA methylation status of RGMa and the clinical
      characteristics of colorectal cancer has not been previously reported. Here, we
      investigated the expression of RGMa by immunohistochemistry, real-time PCR and
      western blotting and analyzed the methylation status of the RGMa promoter using
      Sequenom's MassARRAY platform in colorectal cancer tissues and adjacent normal
      colorectal tissues. The results showed that RGMa expression was decreased in
      cancer tissues compared with adjacent normal tissues (p<0.01). Furthermore, a
      tendency for decreased expression in tumor tissues was observed from Dukes' stage
      A to stage D (p<0.01). In addition, significantly higher levels of
      hypermethylation in promoter regions of RGMa were observed in colorectal cancer
      tissues, compared with those in adjacent normal colorectal tissues (p<0.01).
      Moreover, the methylation levels of RGMa in tumor tissues were significantly
      increased in Dukes' stage C and D compared with Dukes' stage A and B (p<0.01).
      Our results indicate that RGMa expression and promoter methylation status are
      closely related to colorectal cancer genesis and progression. Determination of
      the expression level and methylation frequency of RGMa in colorectal cancer
      tissues may have benefit for early diagnosis and for evaluating patient
      prognosis.

PMID- 22367091
TI  - Cytokines in alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is associated with a spectrum of liver injury
      ranging from steatosis and steatohepatitis to fibrosis and cirrhosis. While
      multifactorial pathogenesis plays a role in the disease progression, enhanced
      inflammation in the liver during ethanol exposure is a major feature of ALD.
      Dysregulated cytokine metabolism and activity are crucial to the initiation of
      alcohol-induced liver injury. The pro-inflammatory cytokine tumor necrosis factor
      (TNF-alpha) has been demonstrated to be one of the key factors in the various
      aspects of pathophysiology of ALD. The immunomodulatory cytokines such as
      interleukin 10 and interleukin 6 play roles in exerting hepatic protective
      effects. Adiponectin is an adipose tissue-derived hormone, which displays
      protective actions on ethanol-induced liver injury. Treatment for mice with
      adiponectin decreases TNF-alpha expression, steatosis and prevents alcohol
      induced liver injury. Adiponectin exerts its anti-inflammatory effects via
      suppression of TNF-alpha expression and induction of anti-inflammatory cytokines
      such as IL-10. Adiponectin attenuates alcoholic liver injury by the complex
      network of multiple signaling pathways in the liver, leading to enhanced fatty
      acid oxidation and reduced steatosis. Interactions between pro- and anti
      inflammatory cytokines such as TNFalpha and adiponectin and other cytokines are
      likely to play important roles in the development and progression of alcoholic
      liver disease.

PMID- 22367092
TI  - Age-related difference in melodic pitch perception is probably mediated by
      temporal processing:  empirical and computational evidence.
AB  - OBJECTIVE: This study was designed to examine whether age-related differences in
      melodic pitch perception may be mediated by temporal processing. Temporal models
      of pitch suggest that performance will decline as the lowest component of a
      complex tone increases in frequency, regardless of age. In addition, if there are
      age-related deficits in temporal processing in older adults, this group may have
      reduced performance relative to younger adults even in the most favorable
      conditions. DESIGN: Six younger adults and 10 older adults with clinically normal
      audiograms up to 8 kHz were tested in a melodic pitch perception task. In each
      trial, two consecutive four-note melodies were presented to the listener.
      Melodies were identical with the exception of one note in the second melody that
      was shifted in pitch. The listener was required to identify which note was
      shifted. All notes consisted of eight successive harmonic components, with the
      average lowest component manipulated to be the 4th, 8th, or 12th component of the
      harmonic series, with lower components being absent. RESULTS: Age-related
      differences in melodic pitch perception were only apparent when stimulus
      parameters favored temporal processing of pitch. Furthermore, modeling a loss of
      periodicity coding yielded an outcome consistent with the observed behavioral
      results. Although younger adults generally outperformed older adults, about one
      quarter of the older adults performed at levels that were equivalent to those of
      younger adults. The only follow-up tests that were able to differentiate these
      exceptional older adults were tests that would be sensitive to temporal
      processing: fundamental frequency difference limens and 500 Hz pure-tone
      difference limens. In contrast, otoacoustic emissions and high-frequency pure
      tone thresholds, which are more commonly associated with spectral processing
      deficits, were not able to differentiate older exceptional adults from older
      typical adults. CONCLUSION: Age-related declines in temporal processing
      contribute to deficits in melodic pitch perception. However, some exceptional
      older adults with normal audiograms preserve excellent temporal processing and
      continue to perform at levels that are typical of younger adults.

PMID- 22367093
TI  - Variations in carrier pulse rate and the perception of amplitude modulation in
      cochlear implant users.
AB  - OBJECTIVES: A major focus of recent attempts to enhance cochlear implant (CI)
      systems has been to increase the rate at which pulses are delivered to the
      electrode array. One basis for these attempts has been the expectation that
      faster stimulation rates would lead to an enhanced representation of temporal
      modulation information. However, there is recent physiological and behavioral
      evidence to suggest that the reverse may be the case. Here, the effects of
      stimulation rate on the perception of amplitude modulation were assessed using
      both modulation detection and modulation frequency discrimination tasks for a
      range of pulse rates extending considerably higher than the highest rate tested
      in previous studies and for different speech-relevant modulation frequencies.
      DESIGN: Detection of sinusoidal amplitude modulation was assessed in five CI
      users using monopolar pulse trains presented to a single electrode at rates of
      482, 723, 1447, 2894, and 5787 pulses per second (pps). Adaptive procedures were
      used to find the minimal detectable modulation depth at modulation frequencies of
      10 and 100 Hz and at carrier levels of 25%, 50%, and 75% of the electrode's
      dynamic range. Discrimination of modulation frequency was examined for the same
      range of pulse rates for the highest carrier level. Similar adaptive procedures
      determined the minimum increase in modulation frequency that could be detected
      relative to reference modulation frequencies of 10, 100, and 200 Hz. In both
      tasks, level roving was implemented to minimize possible loudness cues. RESULTS:
      Consistent with previous evidence, modulation detection thresholds were better
      for higher carrier levels and lower modulation frequencies. When modulation depth
      at threshold was expressed in terms of the ratio of the depth of the modulation
      and the carrier level in dB (i.e., 20 log m), performance was significantly
      better at lower pulse rates. However, when modulation depth was expressed
      relative to dynamic range, the effect of pulse rate was no longer significant,
      reflecting the fact that dynamic range increases with pulse rate. Modulation
      frequency discrimination clearly worsened with increasing modulation frequency,
      but there was no significant effect of pulse rate. CONCLUSIONS: In contrast to
      some recent evidence, no clearly harmful effect of higher pulse rates on
      modulation perception was found. However, even with very fast stimulation rates,
      tested over a wide range of modulation frequencies and with two different tasks,
      there is no evidence of benefit from faster stimulation rates in the perception
      of amplitude modulation.

PMID- 22367094
TI  - Neural encoding and perception of speech signals in informational masking.
AB  - OBJECTIVE: To investigate the contributions of energetic and informational
      masking to neural encoding and perception in noise, using oddball discrimination
      and sentence recognition tasks. DESIGN: P3 auditory evoked potential, behavioral
      discrimination, and sentence recognition data were recorded in response to speech
      and tonal signals presented to nine normal-hearing adults. Stimuli were presented
      at a signal to noise ratio of -3 dB in four background conditions: quiet,
      continuous noise, intermittent noise, and four-talker babble. RESULTS: Responses
      to tonal signals were not significantly different for the three maskers. However,
      responses to speech signals in the four-talker babble resulted in longer P3
      latencies, smaller P3 amplitudes, poorer discrimination accuracy, and longer
      reaction times than in any of the other conditions. Results also demonstrate
      significant correlations between physiological and behavioral data. As latency of
      the P3 increased, reaction times also increased and sentence recognition scores
      decreased. CONCLUSION: The data confirm a differential effect of masker type on
      the P3 and behavioral responses and present evidence of interference by an
      informational masker to speech understanding at the level of the cortex. Results
      also validate the use of the P3 as a useful measure to demonstrate physiological
      correlates of informational masking.

PMID- 22367095
TI  - Tophaceous gout in the elderly: a clinical case review.
AB  - Gout is the most common cause of arthritis in the elderly. Its incidence among
      older people has risen worldwide due to an increase in risk factors such as renal
      diseases, metabolic syndrome, and a diet rich in purines. In older age,
      tophaceous gout may affect different joints from its classical presentation, due
      to other concomitant musculoskeletal diseases, but specific data on its
      epidemiology and clinical aspects in the elderly are limited to a few case
      reports. The present review focuses on the distinctive aspects of tophaceous gout
      in the elderly, revisiting all our clinical cases seen from 1990 to December
      2011. Our findings indicate that: tophaceous gout can affect several joints in
      the elderly, including some unusual sites; its incidence is similar in both
      genders in the elderly even if the latency period between its initial diagnosis
      and the onset of tophi is higher in men; and vertebral localizations are rising
      and often solitary. The components of metabolic syndrome are the most common
      medical conditions associated with tophaceous gout. In conclusion, tophaceous
      gout in the elderly may be a growing medical problem and cause of disability in
      years, partly because of the new sites involved.

PMID- 22367097
TI  - A protein transistor made of an antibody molecule and two gold nanoparticles.
AB  - A major challenge in molecular electronics is to attach electrodes to single
      molecules in a reproducible manner to make molecular junctions that can be
      operated as transistors. Several attempts have been made to attach electrodes to
      proteins, but these devices have been unstable. Here, we show that self-assembly
      can be used to fabricate, in a highly reproducible manner, molecular junctions in
      which an antibody molecule (immunoglobulin G) binds to two gold nanoparticles,
      which in turn are connected to source and drain electrodes. We also demonstrate
      effective gating of the devices with an applied voltage, and show that the charge
      transport characteristics of these protein transistors are caused by
      conformational changes in the antibody. Moreover, by attaching CdSe quantum dots
      to the antibody, we show that the protein transistor can also be gated by an
      applied optical field. This approach offers a versatile platform for
      investigations of single-molecule-based biological functions and might also lead
      to the large-scale manufacture of integrated bioelectronic circuits.

PMID- 22367098
TI  - Molecular electronics: protein transistors strike gold.

PMID- 22367096
TI  - Supernatants from culture of type I collagen-stimulated PBMC from patients with
      cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression
      of MMP-1 by fibroblasts.
AB  - Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by
      vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous
      studies have shown that compared to healthy or diseased controls, the peripheral
      blood mononuclear cells (PBMC) from patients with SSc produce a variety of
      cytokines or proliferate when cultured with solubilized type I collagen (CI) or
      constituent alpha1(II) and alpha2(I) polypeptide chains. The purpose of this
      study was to determine whether PBMC isolated from patients with SSc and cultured
      in vitro with soluble CI elaborated soluble mediators that inhibit the production
      of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts.
      Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous
      (dc)SSc patients significantly reduced MMP-1 production by SSc dermal
      fibroblasts, while supernatants of CI-stimulated PBMC from patients with
      localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from
      patients with dcSSc in contrast to patients with LS exhibited increased levels of
      platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-alpha, IL-13, and EGF.
      Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13
      inhibited the induction of MMP-1 in response to subsequent TNF-alpha stimulation.
      These data suggest that therapies aimed at reducing these cytokines may decrease
      collagen accumulation in SSc, preventing the development of chronic fibrosis.

PMID- 22367099
TI  - Imaging the charge distribution within a single molecule.
AB  - Scanning tunnelling microscopy and atomic force microscopy can be used to study
      the electronic and structural properties of surfaces, as well as molecules and
      nanostructures adsorbed on surfaces, with atomic precision, but they cannot
      directly probe the distribution of charge in these systems. However, another form
      of scanning probe microscopy, Kelvin probe force microscopy, can be used to
      measure the local contact potential difference between the scanning probe tip and
      the surface, a quantity that is closely related to the charge distribution on the
      surface. Here, we use a combination of scanning tunnelling microscopy, atomic
      force microscopy and Kelvin probe force microscopy to examine naphthalocyanine
      molecules (which have been used as molecular switches) on a thin insulating layer
      of NaCl on Cu(111). We show that Kelvin probe force microscopy can map the local
      contact potential difference of this system with submolecular resolution, and we
      use density functional theory calculations to verify that these maps reflect the
      intramolecular distribution of charge. This approach could help to provide
      fundamental insights into single-molecule switching and bond formation, processes
      that are usually accompanied by the redistribution of charge within or between
      molecules.

PMID- 22367101
TI  - Association of genetic polymorphisms in the paraoxonase 1 gene with the risk and
      prognosis of non-small cell lung cancer in Chinese Han population.
AB  - OBJECTIVE: Oxidative stress and free radicals have been indicated to be
      associated with increased risk of various cancers. Paraoxonase 1 (PON1) gene,
      encoding PON1 protein, plays an important role as an endogenous free-radical
      scavenging molecule. The aim of the present study was to determine whether
      genetic polymorphisms of the PON1 gene are associated with the risk and prognosis
      of non-small cell lung cancer (NSCLC). METHODS: A total of 356 patients with
      NSCLC and 184 healthy controls were enrolled in this study. Q192R and L55M
      polymorphisms of the PON1 gene were genotyped using polymerase chain reaction and
      restriction fragment length polymorphism method. RESULTS: As for the Q192R
      polymorphism, the patients with NSCLC showed higher frequencies of QR and RR
      genotypes than the normal controls. Unconditional logistic regression analysis
      revealed that QR and RR genotypes were significantly associated with the presence
      of NSCLC compared with the QQ genotype. No significant differences were found in
      the genotypes of the L55M polymorphism between the patients with NSCLC and the
      healthy controls. The QR and RR genotypes were significantly associated with TNM
      stage and nodal metastasis. Survival analysis indicated that the patients with
      NSCLC with the QR and RR genotypes had poorer disease-free survival than those
      with the QQ genotype (P=0.011). Multivariable Cox regression analysis revealed
      that QR and RR genotypes were an independent factor for the prognosis of NSCLC
      (hazard ratio, 1.505; 95% confidence interval, 1.004-2.256; P=0.048). CONCLUSION:
      The Q192R polymorphism of the PON1 gene may be associated with the risk and
      prognosis of NSCLC in a Chinese Han population.

PMID- 22367100
TI  - Regulation of cerebral cholesterol metabolism in Alzheimer disease.
AB  - Alzheimer disease (AD) is an age-related neurodegenerative disorder that
      manifests as a progressive loss of memory and deterioration of higher cognitive
      functions. Alzheimer disease is characterized by accumulation in the brain of the
      beta-amyloid peptide generated by beta- and gamma-secretase processing of amyloid
      precursor protein. Epidemiological studies have linked elevated plasma
      cholesterol and lipoprotein levels in midlife with AD development. Cholesterol
      fed animal models exhibit neuropathologic features of AD including accumulation
      of beta-amyloid peptide. Specific isoforms of the cholesterol transporter
      apolipoprotein E are associated with susceptibility to AD. Although multiple
      lines of evidence indicate a role for cholesterol in AD, the exact impact and
      mechanisms involved remain largely unknown. This review summarizes the current
      state of our knowledge of the influence of cholesterol and lipid pathways in AD
      pathogenesis in vitro and in vivo.

PMID- 22367102
TI  - Lysinibacillus mangiferahumi sp. nov., a new bacterium producing nematicidal
      volatiles.
AB  - A Gram-positive bacterium, designated M-GX18(T), was isolated from the
      rhizosphere soil of mango (Guangxi Province, China). The isolate produced
      nematicidal volatile compounds with activities against the root-knot nematode
      Meloidogyne incognita. The organism was motile, catalase- and oxidase-positive,
      spore-forming and rod shaped. The predominant menaquinone was MK-7 and the major
      cellular fatty acid profiles were iso-C(15:0), anteiso-C(15:0) and iso-C(16:0).
      The DNA G+C content was 38.9%. A phylogenetic analysis based on 16S rRNA gene
      sequences showed that this organism represented a new species of the genus
      Lysinibacillus. Strain M-GX18(T) exhibited high 16S rRNA gene sequence similarity
      with its closest neighbors Lysinibacillus sphaericus (98.5%), Lysinibacillus
      fusiformis (98.1%) and Lysinibacillus xylanilyticus (98.6%). The physiological,
      biochemical and chemotaxonomic data, including DNA-DNA hybridization relatedness
      data, indicate that strain M-GX18(T) can be distinguished from all the related
      species of the genus Lysinibacillus. Therefore, on the basis of the polyphasic
      taxonomic data presented, a new species of the genus Lysinibacillus,
      Lysinibacillus mangiferahumi, with the type strain M-GX18(T) (=DSM 24076(T) =
      CCTCC AB 2010389(T)) is proposed.

PMID- 22367103
TI  - Photoinduced reversible transmittance modulation of rod-coil type diblock
      copolymers containing azobenzene in the main chain.
AB  - Photoinduced reversible transmittance modulation was achieved with the self
      assembled block copolymer micelles. A large conformational change of the well
      defined rod-coil diblock copolymers containing azobenzene and ether groups in the
      main chain of the rod block induced a remarkable macroscopic change which can be
      observed with the naked eye.

PMID- 22367104
TI  - Morphometric assessment of the hip joint in the Estrela Mountain Dog breed.
AB  - OBJECTIVES: To study the radiographic projected hip parameters of the proximal
      femur and acetabulum in young and adult Estrela Mountain Dogs with normal and
      abnormal hip joints. The parameters evaluated were: femoral angles of inclination
      and anteversion (FAI and FAA), femoral neck length and width (FNL and FNW),
      acetabular depth (AD) and acetabular angle of retrotorsion (AAR). METHODS: Five
      hundred and twenty-five standard hip-extended ventrodorsal radiographic views and
      622 mediolateral views of the right and left femur were used to measure the FAI,
      FAA, FNL, FNW, AD, AAR and modified AAR (mAAR). RESULTS: The FAI decreased in
      adult dysplastic dogs, in females and in right femora; FAA decreased with age;
      FNL was characterized by a greater relative size in normal adult animals; FNW was
      greater in abnormal hips in young and adult animals; AD was less in adult
      dysplastic dogs and in right hips; AAR was similar in the studied groups; mAAR
      was greater in abnormal hips and in left hips. CLINICAL SIGNIFICANCE: The data
      may be used in future studies, which compare this breed to others. Morphological
      variations in femoral neck and acetabular morphometric parameters were present,
      and these variables in dogs with different ages and with hips in varying states
      of health should not be compared.

PMID- 22367105
TI  - Functional outcomes and health-related quality of life in fracture victims 27
      months after the Sichuan earthquake.
AB  - OBJECTIVE: To evaluate functional outcomes, health-related quality of life and
      life satisfaction in fracture victims 27 months after the 2008 Sichuan
      earthquake. METHODS: A total of 390 earthquake survivors from 3 earthquake areas
      who sustained fractures were divided into early intervention, late intervention
      and control groups. Functional outcomes assessed included activities of daily
      living using the Modified Barthel Index and pain level with a visual analogue
      scale. Health-related quality of life was evaluated with the Medical Outcomes
      Study Short-Form 36 and life satisfaction using the Life Satisfaction
      Questionnaire. RESULTS: Activities of daily living and life satisfaction in the
      intervention groups were significantly improved compared with the control group.
      Health-related quality of life was higher in early intervention subjects compared
      with controls. Group differences in pain level were not significant. In addition,
      the early and late intervention groups did not differ significantly in any of the
      measured outcomes. Good performance of activities of daily living and widowed
      marital status predicted high health-related quality of life, while pain level
      was associated with worsened outcomes. Rehabilitation therapy, remunerative
      employment and female gender were predictors of improved life satisfaction.
      CONCLUSION: Clinical effectiveness of physical rehabilitation intervention was
      demonstrated in fracture earthquake victims.

PMID- 22367106
TI  - Random amphiphilic copolymeric sub-micro particles as a carrier shielding from
      enzymatic attack for peptides and proteins delivery.
AB  - The development of peptide drugs and therapeutic proteins is limited by their
      rapid clearance in liver and other body tissues by proteolytic enzymes, and
      consequently peptides and proteins are difficult to administer except by
      injection. There is a growing effort to circumvent these problems by designing
      strategies to deliver these drugs to specific site of the body. Among them, this
      peptide carrier presents several advantages for protein therapy including
      stability in physiological buffer and lack of toxicity. Here, we have been
      developing a novel bioadhesive polymer matrix that protects entrapped proteins
      and peptides from degradation by serine protease. Poly(2-lactobionamidoethyl
      methacrylate-ran-3-acrylamidophenylboronic acid-ran-methoxypolyethylene glycol
      methacrylate) glycopolymers were synthesized and could self-assemble into the sub
      micro particles. The loading capability of insulin, as a drug model, and the
      insulin release from the particles were assessed. The inhibitory effect of the
      particles toward trypsin, elastase, and chymotrypsin was evaluated in vitro.
      Insulin was effectively encapsulated, up to 10%, and could be stained release in
      vitro. These glycopolymers displayed a strong inhibitory effect toward these
      exopeptidases. Therefore, novel glycopolymers with excellent inhibitory activity
      against proteolytic enzymes and reasonable mucoadhesivity might be a useful tool
      in overcoming the enzymatic barrier to the mucosal delivery (e.g. nasal and
      buccal) of therapeutic peptides or proteins.

PMID- 22367107
TI  - Fabrication of a DNA-lipid-apatite composite layer for efficient and area
      specific gene transfer.
AB  - A surface-mediated gene transfer system using biocompatible apatite-based
      composite layers has great potential for tissue engineering. Among the apatite
      based composite layers developed to date, we focused on a DNA-lipid-apatite
      composite layer (DLp-Ap layer), which has the advantage of relatively high
      efficiency as a non-viral system. In this study, various lipid transfection
      reagents, including a newly developed reagent, polyamidoamine dendron-bearing
      lipid (PD), were employed to prepare the DLp-Ap layer, and the preparation
      condition was optimized in terms of efficiency of gene transfer to epithelial
      like CHO-K1 cells in the presence of serum. The optimized DLp-Ap layer derived
      from PD had the highest gene transfer efficiency among all the apatite-based
      composite layers prepared in this study. In addition, the optimized DLp-Ap layer
      demonstrated higher gene transfer efficiency in the presence of serum than the
      conventional particle-mediated systems using commercially available lipid
      transfection reagents. It was also shown that the optimized DLp-Ap layer mediated
      the area-specific gene transfer on its surface, i.e., DNA was preferentially
      transferred to the cells adhering to the surface of the layer. The present gene
      transfer system using the PD-derived DLp-Ap layer, with the advantages of high
      efficiency in the presence of serum and area-specificity, would be useful in
      tissue engineering.

PMID- 22367108
TI  - In vitro release profile of anti-ulcer drug rabeprazole from biocompatible
      psyllium-PVA hydrogels.
AB  - The present article discusses the synthesis, characterization and
      haemocompatibility behaviour of the psyllium-PVA hydrogels prepared by chemical
      method in the presence of N,N'-methylenebisacrylamide. These hydrogels have been
      characterized by Fourier Transform infrared spectroscopy, thermo gravimetric
      analysis, swelling and drug release studies. The release of model drug
      rabeprazole sodium from the drug loaded hydrogels occurred through non-Fickian
      diffusion mechanism. Psyllium itself acts as anti-ulcer agent and release of
      rabeprazole from the drug loaded hydrogels may enhance the curing potential of
      the drug delivery device. The haemocompatibility was evaluated by studying the
      blood interactions with hydrogels with reference to thrombogenicity and
      haemolytic potential. Thrombogenicity results indicate that hydrogels are non
      thrombogenic as the weight of clot formed and thrombus percentage for hydrogels
      was less than the positive control. The haemolytic index has been observed <5%.
      These observations indicate that these hydrogels are haemo-compatible and hence
      could be used for oral administration of antiulcer drugs.

PMID- 22367109
TI  - Cytisine: a natural product lead for the development of drugs acting at nicotinic
      acetylcholine receptors.
AB  - Covering: up to the end of 2011. This review covers classical and modern
      structural modifications of the alkaloid, the more recent (since 2007) syntheses
      of cytisine and analogues, and the pharmacology of these compounds, with emphasis
      on their interactions with nicotinic receptors. 89 references are cited.

PMID- 22367110
TI  - Intertribal hybrid plants produced from crossing Arabidopsis thaliana with
      apomictic Boechera.
AB  - Arabidopsis thaliana and Boechera belong to different tribes of the Brassicaceae
      and last shared a common ancestor 13-35 million years ago. A. thaliana reproduces
      sexually but some Boechera accessions reproduce by apomixis (asexual reproduction
      by seed). The two species are reproductively isolated, preventing introgression
      of the trait(s) controlling apomixis from Boechera into A. thaliana and their
      molecular characterisation. To identify if "escapers" from such hybridisation
      barriers exist, we crossed diploid or tetraploid A. thaliana mothers carrying a
      conditional male sterile mutation with a triploid Boechera apomict. These cross
      pollinations generated zygotes and embryos. Most aborted or suffered multiple
      developmental defects at all stages of growth, but some seed matured and
      germinated. Seedlings grew slowly but eventually some developed into mature
      plants that were novel synthetic allopolyploid hybrids. With one exception,
      intertribal hybrids contained three Boechera plus either one or two A. thaliana
      genomes (depending on maternal ploidy) and were male and female sterile. The
      exception was a semi-fertile, sexual partial hybrid with one Boechera plus two A.
      thaliana genomes. The synthesis of "escapers" that survive rigorous early
      developmental challenges in crosses between A. thaliana and Boechera demonstrates
      that the inviability form of postzygotic reproductive isolation separating these
      distantly related species is not impenetrable. The recovery of a single semi
      fertile partial hybrid also demonstrates that hybrid sterility, another form of
      postzygotic reproductive isolation, can be overcome between these species.

PMID- 22367111
TI  - Primary thyroid lymphoma: the 40 year experience of a UK lymphoma treatment
      centre.
AB  - We report the 40-year unselected experience of a UK lymphoma treatment centre.
      Between 1970 and 2010, 3363 cases of non-Hodgkin lymphoma were managed by the
      Sheffield Lymphoma Team. Seventy cases of primary thyroid lymphoma were
      identified during this time. This retrospective review of the clinical and
      pathological features of patients with thyroid lymphoma comprises one of the
      largest series conducted in the UK. The series included 57 females and 13 males
      with a median age at diagnosis of 69.5. The pathological subtypes were diffuse
      large B-cell lymphoma (DLBCL) in 50 patients, MALT lymphoma in 13, indolent B
      cell lymphoma not otherwise specified (NOS) in 6 and T cell lymphoma in one
      patient. Of the 64 patients fully staged, 53 had Stage IE and 11 Stage IIE
      disease. Management modalities included surgery, chemotherapy, radiotherapy or
      combination treatment. Five- year survival rates for DLBCL, MALT lymphoma and
      indolent B-cell lymphoma NOS were 45%, 62% and 75%, respectively, with a median
      overall survival of all histological subtypes of 68 months (range 0-148) or 5.7
      years. The outcomes of this series confirm previous experience. If treatment is
      needed after surgery radiotherapy alone is sufficient for Stage I and II low
      grade thyroid lymphoma. Combination chemotherapy or adequate chemotherapy
      followed by radiotherapy is warranted in high grade thyroid lymphoma.

PMID- 22367112
TI  - Performance of platelet count/spleen diameter ratio for diagnosis of esophageal
      varices in cirrhosis: a meta-analysis.
AB  - BACKGROUND: Platelet count/spleen diameter ratio (PSR) is a non-invasive method
      for the assessment of esophageal varices (EV), developed as an alternative to
      endoscopy. AIM: To assess the performance of PSR for diagnosis of EV using meta
      analysis. METHODS: PubMed, EMBASE, the Cochrane Library, ISI web of Knowledge,
      China National Knowledge Infrastructure, and article references were searched. We
      included studies using endoscopy as a reference standard, with the data necessary
      to calculate the true and false positive, true and false negative diagnostic
      results of PSR for EV. The quality of the studies was rated with the QUADAS tool.
      The hierarchical summary receiver operating characteristic (HSROC) was used to
      examine the PSR accuracy for the diagnosis of EV. Heterogeneity was explored
      using meta-regression. Clinical utility of PSR for EV was evaluated by a Fagan
      plot. RESULTS: In 20 studies (n = 3,063), the HSROC of the PSR for EV was 0.95 at
      various thresholds. At the threshold of 909, the summary sensitivities and
      specificities were 0.92 (95% CI, 0.79-0.97) and 0.87 (95% CI, 0.76-0.93),
      respectively. The HSROC was also 0.95 at the threshold of 909. If PSR was below
      909 for EV ("positive" result), the post-test probability (if pre-test
      probability was 50%) was 87%, while if PSR was at or over 909 ("negative"
      result), the post-test probability was only 9%. PSR also had a high accuracy in
      diagnosis of EV in patients with compensated cirrhosis. CONCLUSIONS: PSR can
      identify EV in cirrhosis with a high accuracy. Application of this index may
      decrease the need for endoscopy among cirrhotic patients.

PMID- 22367115
TI  - On the presence of serotonin in mammalian cardiomyocytes.
AB  - Pleiotropic effects of serotonin (5-HT) in the cardiovascular system are well
      documented. However, it remains to be elucidated, whether 5-HT is present in
      adult mammalian cardiomyocytes. To address this issue, we investigated the levels
      of 5-HT in blood, plasma, platelets, cardiac tissue, and cardiomyocytes from
      adult mice and for comparison in human right atrial tissue.
      Immunohistochemically, 5-HT was hardly found in mouse cardiac tissue, but small
      amounts could be detected in renal preparations, whereas adrenal preparations
      revealed a strong positive immunoreaction for 5-HT. Using a sensitive HPLC
      detection system, 5-HT was also detectable in the mouse heart and human atrium.
      Furthermore, we could identify 5-HT in isolated cardiomyocytes from adult mice.
      These findings were supported by detection of the activity of 5-HT-forming
      enzymes-tryptophan hydroxylase and aromatic L-amino acid decarboxylase-in
      isolated cardiomyocytes from adult mice and by inhibition of these enzymes with p
      chlorophenylalanine and 3-hydroxybenzyl hydrazine. Addition of the first
      intermediate of 5-HT generation, that is 5-hydroxytryptophan, enhanced the 5-HT
      level and inhibition of monoamine oxidase by tranylcypromine further increased
      the level of 5-HT. Our findings reveal the presence and synthesis of 5-HT in
      cardiomyocytes of the mammalian heart implying that 5-HT may play an autocrine
      and/or paracrine role in the heart.

PMID- 22367114
TI  - A study on the efficacy of rebamipide for patients with proton pump inhibitor
      refractory non-erosive reflux disease.
AB  - BACKGROUND AND AIM: Reflux symptoms in patients with non-erosive reflux disease
      (NERD) cannot be easily controlled by treatment with proton pump inhibitors
      (PPI). The anti-inflammatory function of rebamipide may be effective for
      protecting the esophageal mucosa. This prospective randomized multicenter placebo
      controlled study was performed to clarify the efficacy of rebamipide for NERD
      patients whose reflux symptoms were refractory to PPI treatment. METHODS: One
      hundred forty-nine patients were enrolled on the basis of a QUEST score of over 6
      and absence of endoscopically proven esophageal mucosal breaks. All the patients
      were initially administered 15 mg of lansoprazole for 4 weeks, and the symptoms
      were then assessed using QUEST and GSRS. PPI-refractory patients were randomly
      assigned to administration of rebamipide or placebo t.i.d. for 4 weeks. RESULTS:
      Three of the 149 patients were lost to follow-up, and 60 among the remaining 146
      patients were found to be PPI-refractory. Among these PPI-refractory patients, 31
      were randomly assigned to a rebamipide group and 29 to a placebo group. At the
      end of drug administration, the QUEST and GSRS scores did not differ between the
      rebamipide and placebo groups, although a significantly higher proportion of
      patients in the rebamipide group showed amelioration of abdominal pain and
      diarrhea. CONCLUSION: Administration of rebamipide cannot effectively control
      reflux symptoms in NERD patients whose symptoms are refractory to PPI therapy.

PMID- 22367116
TI  - Preclinical pharmacology of novel indolecarboxamide ML-970, an investigative
      anticancer agent.
AB  - PURPOSE: ML-970 (AS-I-145; NSC 716970) is an indolecarboxamide synthesized as a
      less toxic analog of CC-1065 and duocarmycin, a natural product that binds the A
      T-rich DNA minor groove and alkylates DNA. The NCI60 screening showed that ML-970
      had potent cytotoxic activity, with an average GI(50) of 34 nM. The aim of this
      study is to define the pharmacological properties of this novel anticancer agent.
      METHODS: We established an HPLC method for the compound, examined its stability,
      protein binding, and metabolism by S9 enzymes, and conducted pharmacokinetic
      studies of the compound in two strains of mice using two different formulations.
      RESULTS: ML-970 was relatively stable in plasma, being largely intact after an 8
      h incubation in mouse plasma at 37 degrees C. The compound was extensively bound
      to plasma proteins. ML-970 was only minimally metabolized by the enzymes present
      in S9 preparation and was not appreciably excreted in the urine or feces. The
      solution formulation provided higher C(max), AUC, F values, and greater
      bioavailability, although the suspension formulation resulted in a later T(max)
      and a slightly longer T(1/2). To determine the fate of the compound, we
      accomplished in-depth studies of tissue distribution; the results indicated that
      the compound undergoes extensive enterohepatic circulation. CONCLUSIONS: The
      results obtained from this study will be relevant to the further development of
      the compound and may explain the lower myelotoxicity of this analog compared to
      CC-1065.

PMID- 22367113
TI  - The physiology of human defecation.
AB  - Human defecation involves integrated and coordinated sensorimotor functions,
      orchestrated by central, spinal, peripheral (somatic and visceral), and enteric
      neural activities, acting on a morphologically intact gastrointestinal tract
      (including the final common path, the pelvic floor, and anal sphincters). The
      multiple factors that ultimately result in defecation are best appreciated by
      describing four temporally and physiologically fairly distinct phases. This
      article details our current understanding of normal defecation, including recent
      advances, but importantly identifies those areas where knowledge or consensus is
      still lacking. Appreciation of normal physiology is central to directed treatment
      of constipation and also of fecal incontinence, which are prevalent in the
      general population and cause significant morbidity.

PMID- 22367117
TI  - Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via
      simultaneous induction of apoptosis and autophagy.
AB  - Evodiamine, an alkaloid isolated from Evodia rutaecarpa, possesses potent
      anticancer activity. Although many reports have elucidated the cytotoxic effects
      of evodiamine in a variety of cancer cells, little is known about the mechanism
      of evodiamine-induced cytotoxic activity in gastric cancer cells. To date, no
      report has addressed the synchronized role of autophagy and apoptosis in
      evodiamine-induced cytotoxic activity. This study was conducted to investigate
      the synchronized role of autophagy and apoptosis in evodiamine-induced cytotoxic
      activity on SGC-7901 human gastric adenocarcinoma cells and further to elucidate
      the underlying molecular mechanisms. The MTT assay was used to examine the
      cytotoxicity of evodiamine against SGC-7901 gastric adenocarcinoma cells. The
      effects of evodiamine on the cell cycle and apoptosis were measured by flow cyto
      metry and cellular morphology was observed under a phase contrast microscope.
      Acridine orange (AO) staining was used to detect autophagy. The expression levels
      of Bcl-2 and Bax were detected by Western blotting. The expression level of
      Beclin-1 in SGC-7901 cells was monitored by reverse transcription-polymerase
      chain reaction (RT-PCR). Here, we found that evodiamine significantly inhibited
      the proliferation of SGC-7901 cells and induced G2/M phase cell cycle arrest.
      Furthermore, both autophagy and apoptosis were activated during the evodiamine
      induced death of SGC-7901 cells. Evodiamine-induced autophagy is partially
      involved in the death of SGC-7901 cells which was confirmed by using the
      autophagy inhibitor 3-methyladenine (3-MA). Additionally, Beclin-1 is involved in
      evodiamine-induced autophagy and the pro-apoptotic mechanisms of evodiamine may
      be associated with down-regulation of Bcl-2 and up-regulation of Bax expression.
      The inhibitory effects on SGC-7901 cells were associated with apoptosis,
      autophagy and cell cycle arrest at the G2/M phase in a dose-dependent manner.
      These results suggest that evodiamine is an effective natural compound for the
      treatment of gastric cancer and may represent a candidate for in vivo studies of
      monotherapies or combined antitumor therapies.

PMID- 22367119
TI  - Aluminium sulphate exposure increases oxidative stress and suppresses brain
      development in Ross broiler chicks.
AB  - BACKGROUND: Aluminium (Al) is known to have neurotoxic effects that can result in
      oxidative damage to a range of cellular biomolecules. These effects appear to be
      of significance in the developmental stages of the brain. We therefore
      investigated the oxidative and histopathological damage induced by Al during
      growth and development of the chick brain. MATERIAL/METHODS: We used a chick
      embryonic development model, with Al treatment of 500 ug Al sulphate in 0.1 ml
      saline injected into the egg air chambers at the beginning of their incubation
      period. The effects on chick-brain growth and development were then assessed at
      term (day 21). Determination of malondialdehyde and glutathione levels were used
      as relevant biological measures for increased oxidative stress in terms of lipid
      peroxidation and biochemical oxidative damage, respectively. Furthermore, we also
      monitored neuronal degeneration as estimated stereologically using the Cavalieri
      brain volume estimation tool. RESULTS: This Al treatment showed significantly
      increased MDA levels and decreased GSH levels, as indicators of increased
      biochemical oxidative damage. This was accompanied by significantly decreased
      brain volume, as a measure of neuronal degeneration during brain development in
      this chick embryonic development model. CONCLUSIONS: Exposure to Al during chick
      embryonic development results in increased oxidative stress in the brain that is
      accompanied by neuronal degeneration.

PMID- 22367118
TI  - Constraining the metabolic genotype-phenotype relationship using a phylogeny of
      in silico methods.
AB  - Reconstructed microbial metabolic networks facilitate a mechanistic description
      of the genotype-phenotype relationship through the deployment of constraint-based
      reconstruction and analysis (COBRA) methods. As reconstructed networks leverage
      genomic data for insight and phenotype prediction, the development of COBRA
      methods has accelerated following the advent of whole-genome sequencing. Here, we
      describe a phylogeny of COBRA methods that has rapidly evolved from the few early
      methods, such as flux balance analysis and elementary flux mode analysis, into a
      repertoire of more than 100 methods. These methods have enabled genome-scale
      analysis of microbial metabolism for numerous basic and applied uses, including
      antibiotic discovery, metabolic engineering and modelling of microbial community
      behaviour.

PMID- 22367120
TI  - The normal growth of the common iliac arteries in human fetuses - an anatomical,
      digital and statistical study.
AB  - BACKGROUND: The present study was carried out to compile normative data for
      dimensions of the common iliac arteries at varying gestational ages.
      MATERIAL/METHODS: We used anatomical dissection, digital-image analysis (system
      of Leica QWin Pro 16) and statistical analysis (Student T test, one-way ANOVA,
      post-hoc RIR Tukey test, and regression analysis) to examine the increase in
      length (mm), proximal external diameter (mm), and volume (mm3) of the common
      iliac arteries in 124 (60 males, 64 females) spontaneously aborted human fetuses
      aged 15-34 weeks. RESULTS: Neither sex nor right-left significant differences
      were found (P>0.05). The length ranged from 4.76 +/- 1.05 to 15.38 +/- 1.60 mm on
      the right, and from 4.92 +/- 1.33 to 14.91 +/- 1.25 mm on the left, according to
      the linear functions y=-3.598+0.585 * Age +/- 1.522 (R2=0.83) and y=-3.107+0.554
      * Age +/- 1.444 (R2=0.83). The proximal external diameter increased from 0.66 +/-
      0.19 to 2.30 +/- 0.42 mm on the right, and from 0.66 +/- 0.14 to 2.16 +/- 0.42 mm
      on the left, according to the quadratic models y=1.392-0.110 * Age + 0.004 * Age2
      +/- 0.285 (R2=0.77) and y=1.283-0.099 * Age + 0.004 * Age2 +/- 0.238 (R2=0.81).
      The volumes were increasing from 1.93 +/- 1.74 to 66.95 +/- 29.31 mm3 on the
      right, and from 1.91 +/- 1.65 to 56.86 +/- 25.17 mm3 on the left, given by the
      quadratic functions: y=99.69-10.60 * Age+0.28 7 * Age2 +/- 14.40 (R2=0.67) and
      y=82.62-8.86 * Age + 0.242 * Age2 +/- 11.60 (R2=0.71). CONCLUSIONS: The common
      iliac arteries grow linearly in length, and parabolically in both diameter and
      volume. The right common iliac artery constitutes a predominant vessel in
      relation to its length, external diameter and volume. The morphometric data on
      the common iliac arteries may serve as a useful reference in the prenatal
      diagnosis and monitoring of congenital aorto-iliac abnormalities.

PMID- 22367121
TI  - Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated
      BALB/c mice.
AB  - BACKGROUND: Recent studies show that molecular hydrogen (dihydrogen, H2) has
      potential as an effective and safe radioprotective agent through reducing
      oxidative stress. The aim of this study was to investigate whether H2 is able to
      protect spermatogenesis and hematopoiesis from radiation-induced injuries.
      MATERIAL/METHODS: H2 was dissolved in physiological saline using an apparatus
      produced by our department. -60Co-gamma rays in the irradiation centre were used
      for irradiation. Spermatid head counts and histological analysis were used to
      evaluate spermatogenesis. Endogenous hematopoietic spleen colony formation
      (endoCFUs), bone marrow nucleated cells (BMNC) and peripheral blood (PB)
      leukocytes were used to evaluate hemopoiesis. RESULTS: This study demonstrates
      that treating mice with H2 before ionizing radiation (IR) can increase the
      spermatid head count and protect seminiferous epithelium from IR. This study also
      demonstrates that H2 could significantly increase the number of endoCFUs, BMNC
      and PB leukocyte. CONCLUSIONS: This study suggests that hydrogen-rich saline
      could partially protect spermatogenesis and hematopoiesis in irradiated mice.

PMID- 22367122
TI  - Effects of systemic ornidazole, systemic and local compound ornidazole and
      pefloxacin mesylate on experimental periodontitis in rats.
AB  - BACKGROUND: The purpose of the current study is to evaluate the effects of
      systemic ornidazole (SO) and systemic and local compound ornidazole and
      pefloxacin mesylate (SCOPM/LCOMP) on the inflammatory response associated with
      rat experimental chronic periodontitis (ECP) in sites with subgingival
      debridement. MATERIAL/METHODS: Periodontitis was induced in male Sprague-Dawley
      rats by placing a thin steel ligature around the upper first molars and
      inoculating them with Porphyromonas gingivalis 381. After the successful
      induction of the rat ECP, the periodontitis rats were randomly divided into 3
      different combined treatment groups: (A) SO with scaling and root planing (SRP);
      (B) SCOMP with SRP; and (C) LCOMP with SRP. After 2 weeks the effects of the
      treatments were evaluated based on gingivitis, plaque index, probing pocket
      depth, aspartate aminotransferase, alveolar bone loss, and hematoxylin-eosin
      staining of the region around the first molars. RESULTS: After treatment,
      comparison with ECP was performed. The mean percentage reductions of SBI in SO,
      SCOPM, and LCOPM were 27.73%, 33.61%, and 58.82%, respectively. Those of PI were
      33.20%, 42.80%, and 60.00%; those of PPD were 48.66%, 55.70%, and 72.48%; those
      of GCF-AST were 41.64%, 49.03%, and 66.42%; and those of ABL were 41.19%, 43.63%,
      and 54.47%, respectively. The inflammatory score of H&E showed median scores of
      2.5, 1.75, 1.63, and 0.95 for ECP, SO, SCOMP, and LCOMP, respectively. All 3
      treatment groups exhibited significantly reduced inflammation indicators
      (P<0.05). Of the 3, group C was the most effective (P<0.05). CONCLUSIONS:
      Although all the combined treatment groups responded to therapy with significant
      resolution of the infection, adjunctive LCOMP therapy is more effective for
      periodontitis.

PMID- 22367123
TI  - Incidence of new cardiovascular events in patients with and without peripheral
      arterial disease seen in a vascular surgery clinic.
AB  - BACKGROUND: To investigate the incidence of death and of new cardiovascular
      events at long-term follow-up of patients with and without PAD seen in a vascular
      surgery clinic. MATERIAL/METHODS: We investigated the incidence of death, new
      stroke/transient ischemic attack, new myocardial infarction, new coronary
      revascularization, new carotid endarterectomy, new peripheral arterial disease
      (PAD) revascularization, or at least one of the above outcomes at long-term
      follow-up of patients with and without PAD followed in a vascular surgery clinic.
      RESULTS: At least one of the above outcomes occurred in 259 of 414 patients (63%)
      with PAD at 33-month follow-up and in 21 of 89 patients (24%) without PAD at 48
      month follow-up (p<0.0001). Death occurred in 112 of 414 patients (27%) with PAD
      and in 10 of 89 patients (11%) without PAD (p=0.002). Stepwise Cox regression
      analysis for the time to at least one of the 6 outcomes showed that significant
      independent risk factors were men (hazard ratio =1.394; 95% CI, 1.072-1.813;
      p=0.013), estimated glomerular filtration rate (hazard ratio =0.992; 95% CI,
      0.987-0.997; p=0.003), and PAD (hazard ratio =3.520; 95% CI, 2.196-5.641;
      p<0.0001). Stepwise Cox regression analysis for the time to death showed that
      significant independent risk factors were age (hazard ratio =1.024; 95% CI, 1.000
      1.049; p=0.048), estimated glomerular filtration rate (hazard ratio =0.985; 95%
      CI, 0.974-0.996; p=0.007), and PAD (hazard ratio =2.157; 95% CI, 1.118-4.160;
      p=0.022). CONCLUSIONS: Patients with PAD have a significantly higher incidence of
      cardiovascular outcomes, especially death, new PAD revascularization, and new
      carotid endarterectomy, than patients without PAD followed in a vascular surgery
      clinic.

PMID- 22367125
TI  - Effects of pellet stove on recovery from mental fatigue.
AB  - BACKGROUND: Exposure to a warm environment has been reported to be effective for
      recovery from mental fatigue. However, there have been no reports examining the
      effects of a pellet stove on recovery from mental fatigue. The purpose of this
      study was to examine the effects of a pellet stove on recovery from mental
      fatigue. MATERIAL/METHODS: In this placebo-controlled, crossover experiment, 16
      healthy volunteers were randomized into the pellet stove and control groups.
      After a 30-min fatigue-inducing mental task session, participants moved to a
      recovery room with (pellet stove condition) or without (control condition) a
      pellet stove to see the image of a pellet stove for 30 min. RESULTS: After the
      recovery session, the participants exposed to the pellet stove condition showed
      lower total error counts of a cognitive test, higher levels of subjective
      healing, comfort, and warmth, and sympathetic nerve activity and higher
      parasympathetic nerve activity as compared with the control condition.
      CONCLUSIONS: These results provide evidence that improved cognitive function,
      subjective mental states, and balance of the autonomic nervous activities result
      from using a pellet stove during the recovery session. Hence, the pellet stove
      was effective for the recovery from mental fatigue.

PMID- 22367124
TI  - Different patterns of language activation in post-stroke aphasia are detected by
      overt and covert versions of the verb generation fMRI task.
AB  - BACKGROUND: Post-stroke language functions depend on the relative contributions
      of the dominant and non-dominant hemispheres. Thus, we aimed to identify the
      neural correlates of overt and covert verb generation in adult post-stroke
      aphasia. MATERIAL AND METHODS: Sixteen aphasic LMCA stroke patients (SPs) and 32
      healthy controls (HCs) underwent language testing followed by fMRI while
      performing an overt event-related verb generation task (ER-VGT) isolating
      activations related to noun-verb semantic processing or to articulation and
      auditory processing, and a covert block design verb generation task (BD-VGT).
      RESULTS: BD-VGT activation patterns were consistent with previous studies, while
      ER-VGT showed different patterns in SPs relative to HCs including less left
      hemispheric involvement during semantic processing and predominantly right-sided
      activation related to articulation and auditory processing. ER-VGT intra-scanner
      performance was positively associated with activation during semantic
      associations in the left middle temporal gyrus for HCs (p=0.031) and left middle
      frontal gyrus for SPs (p=0.042). Increased activation in superior
      frontal/cingulate gyri was associated with better intra-scanner performance
      (p=0.020). Lesion size negatively impacted verbal fluency tested with Controlled
      Oral Word Association Test (p=0.0092) and the Semantic Fluency Test (p=0.033) and
      trended towards a negative association with verb generation performance on the
      event-related verb generation task (p=0.081). CONCLUSION: Greater retention of
      pre-stroke language skills is associated with greater involvement of the left
      hemisphere with different cortical recruitment patterns observed in SPs versus
      HCs. Post-stroke verbal fluency may depend more upon the structural and
      functional integrity of the dominant left hemisphere language network rather than
      the shift to contralateral homologues.

PMID- 22367126
TI  - Examination of chemosensory functions in patients with dysosmia.
AB  - BACKGROUND: To examine changes of chemical sensory functions in patients with
      dysosmia. MATERIAL/METHODS: The 272 study subjects included 98 healthy
      volunteers, 86 subjects with hyposmia and 88 subjects with functional anosmia.
      Their chemical sensory functions were examined using olfactory event-related
      potentials (oERPs), trigeminal event-related potentials (tERPs), T&T olfactometer
      and triple drop method, respectively. RESULTS: The T&T results showed that the
      difference between patients and healthy subjects had statistical significance.
      The oERPs and tERPs results showed that patients with functional anosmia had N1
      and P2 waves of prolonged latency and reduced amplitude when compared to healthy
      subjects with the difference of statistical significance. When compared to
      healthy subjects, patients with functional anosmia had clear hypogeusia and the
      difference had statistical significance. For the younger group there was
      significant difference between healthy subjects and patients in T&T, oERPs and
      tERPs results. CONCLUSIONS: It is suggested by the apparently concomitant
      trigeminal nerve dysfunction and hypogeusia in patients with functional anosmia
      in this study that olfactory and nasal trigeminal function in young patients was
      clearly decreased. Our study suggests the possible application of oERPs, tERPs
      and three drops method in clinical diagnosis in Chinese populations and provides
      scientific evidence for treatment.

PMID- 22367128
TI  - A randomized controlled trial to determine the effect of spinal stabilization
      exercise intervention based on pain level and standing balance differences in
      patients with low back pain.
AB  - BACKGROUND: A number of studies have evaluated exercise interventions compared
      with other treatment strategies for subjects with recurrent low back pain (LBP);
      however, subject pain level and balance were not carefully considered. The
      purpose of this study was to investigate the effectiveness of spinal
      stabilization exercises (SSE) for managing pain and increasing balance strategy
      changes following unexpected perturbations in patients diagnosed with recurrent
      LBP. MATERIAL/METHODS: Twenty-one age- and gender-matched patients participated
      in a supervised SSE or control exercise program 5 times a week over a 4-week
      period. The Million Visual Analogue Scale (MVAS) and Oswestry Disability Index
      (ODI) were used to measure each patient's level of pain and disability. Balance
      measurements were derived from recordings of the anterior-posterior (A/P) and
      medio-lateral (M/L) center of pressure (COP) displacements during 3 consecutive,
      unexpected random perturbations. RESULTS: The level of reported pain and
      disability significantly decreased following treatment for both groups. Although
      the M/L sway was not significantly different in either group (p=0.86), there was
      a significant difference between group and measurement time during A/P sway
      (p=0.04). The A/P displacement of the SSE group significantly decreased compared
      with the control group. The decreased A/P displacement can be linked to the SSE
      intervention, which helps prevent further injury by limiting an individual's
      response rate to external perturbations. CONCLUSIONS: Clinicians might consider
      SSE for LBP patients as a possible rehabilitation strategy to reduce A/P
      displacement.

PMID- 22367127
TI  - Characteristics of subjects with comorbidity of symptoms of generalized anxiety
      and major depressive disorders and the corresponding threshold and subthreshold
      conditions in an Arab general population sample.
AB  - BACKGROUND: There is controversy about differential meaningfulness between
      comorbid generalized anxiety disorder (GAD)/ major depressive disorder (MDD), the
      corresponding "pure" disorders and subthreshold conditions. We compared subjects
      who met DSM-IVTR criteria of symptoms and functional impairment for comorbid
      GAD/MDD, versus those with GAD, MDD, subthreshold conditions, and without
      significant symptoms. The comparison measures were socio-demographics, clinical
      severity, and quality of life (QOL). MATERIAL/METHOD: Participants (N=3155: 55.1%
      female, aged 16-87 yrs) were a general population sample of Kuwaitis who self
      completed DSM-IVTR criteria-based questionnaires and the WHOQOL-BREF in 2006/7.
      We scrutinized the questionnaires and classified them into categories. RESULTS:
      Of the 273 GAD and 210 MDD cases, the prevalence of comorbidity among cases with
      GAD was 30.8%, and 40% among MDD. Of the 398 subthreshold GAD and 194
      subthreshold MDD cases, 58 had subthreshold anxiety/depression comorbidity.
      Comorbid threshold GAD/MDD cases were significantly older, and more likely to be
      women, divorced and unemployed, compared with GAD and MDD. In all measures, the
      threshold GAD/MDD comorbidity was the severest condition. There was a monotonic
      decrease in QOL with increasing anxiety-depression symptoms. For the predictors
      of subjective QOL, the GAD/MDD comorbidity group differed markedly from the
      others. CONCLUSIONS: The high prevalence of comorbidity and subthreshold
      conditions supports the recommendation to assess them routinely, regardless of
      the primary reason for consultation. Our findings support a dimensional model
      with comorbid GAD/MDD at the higher end of a continuum, and differing from the
      "pure" conditions by a later onset and predictors of subjective wellbeing.

PMID- 22367129
TI  - Aggressive and impulsive behavior in Alzheimer's disease and progression of
      dementia.
AB  - BACKGROUND: The symptoms of Alzheimer's disease (AD) are numerous, including
      worsening of mood, psychotic symptoms, aggressive and impulsive behaviours, and
      many others. It is generally assumed that there exists a relationship between the
      severity of dementia and aggressive symptoms. The aim of this study was to assess
      the relationship between aggressive and impulsive behaviours and cognitive
      function disorders in AD patients. MATERIAL/METHODS: Forty-eight AD patients
      living in a nursing home were included in the research group on the basis of
      NINCDS/ADRDA criteria. The subjects underwent two years of naturalistic
      observation. The intensity of agitation and aggressive behaviours was assessed on
      the basis of the Cohen-Mansfield Agitation Inventory (CMAI). The Alzheimer's
      Disease Assessment Scale Cog (ADAS-cog) was used to assess cognitive function.
      Pharmacotherapy administered during the observation period was also taken into
      account. RESULTS: Thirty-one patients completed the two year long observation.
      Individuals with more severe cognitive deficiencies demonstrated a greater
      intensity of aggressive and impulsive behaviours, as assessed using the CMAI
      scale. Aggression escalated together with the development of dementia disorders.
      The intensity of dementia disorders was most significantly connected with
      physical agitation and verbal aggression. The use of neuroleptics and mood
      stabilisers decreased the progression of aggressive and impulsive behaviours.
      CONCLUSIONS: There is a relationship between cognitive functioning disorders and
      the intensification of aggressive and impulsive behaviours. More severe forms of
      dementia are connected with greater intensification of aggressive and impulsive
      behaviours as the disease progresses. Periodical administration of
      pharmacotherapy may reduce the development of aggressive behaviours.

PMID- 22367130
TI  - Analysis of the relation between level of asthma control and depression and
      anxiety.
AB  - BACKGROUND: Frequent co-existence of bronchial asthma and depression or anxiety
      is an unquestioned phenomenon. In contrast, little is known about the
      relationship between the degree of asthma control and the prevalence of
      depression and anxiety. The aim of this study was to determine the potential
      relationship between the degree of asthma control and the prevalence of
      depression and anxiety. MATERIAL/METHODS: This study included a group of 128
      randomly selected asthmatic individuals with various degree of asthma control.
      The study was based on a questionnaire survey, using the following tools: the
      Asthma Control Test, Beck Depression Inventory, and State-Trait Anxiety Inventory
      (STAI) - X-1 and X-2 questionnaires. All the questionnaires were completed during
      a single follow-up visit at the clinic. RESULTS: The occurrence of depression and
      its severity significantly correlated with the degree of asthma control.
      Individuals with depression were characterized by a significantly lower degree of
      asthma control compared to depression-free individuals (p<0.001). The degree of
      asthma control decreased significantly with increasing severity of depression (R=
      0.367; p<0.001). No significant correlation was observed between the degree of
      asthma control and the levels of trait anxiety (R=-0.095; p=0.295) and state
      anxiety (R=-0.093; p=0.308). CONCLUSIONS: The prevalence of depression and its
      severity significantly correlate with the degree of asthma control. Large,
      standardized multicenter studies of the relationship between the degree of asthma
      control and the prevalence of depression and other psychopathological symptoms
      are needed. Furthermore, it seems reasonable to introduce the screening of
      asthmatics for mental disorders.

PMID- 22367131
TI  - Comparative study of the retinal nerve fibre layer thickness performed with
      optical coherence tomography and GDx scanning laser polarimetry in patients with
      primary open-angle glaucoma.
AB  - BACKGROUND: We compared the parameters of retinal nerve fibre layer in patients
      with advanced glaucoma with the use of different OCT (Optical Coherence
      Tomograph) devices in relation to analogical measurements performed with GDx VCC
      (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser
      polarimetry. MATERIAL/METHODS: Study subjects had advanced primary open-angle
      glaucoma, previously treated conservatively, diagnosed and confirmed by
      additional examinations (visual field, ophthalmoscopy of optic nerve,
      gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18-70
      years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined.
      1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of
      optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2)
      performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3)
      measuring the retinal nerve fibre layer thickness with 3 different optical
      coherence tomographs. RESULTS: The parameters of the retinal nerve fibre layer
      thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000
      devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer
      thickness in the upper sector, and correlation of NFI (GDx) with mean retinal
      nerve fibre layer thickness in OCT examinations. Absolute values of the retinal
      nerve fibre layer thickness (measured in um) differ significantly between GDx and
      all OCT devices. CONCLUSIONS: Examination with OCT devices is a sensitive
      diagnostic method of glaucoma, with good correlation with the results of GDx
      scanning laser polarimetry of the patients.

PMID- 22367132
TI  - Multidisciplinary treatment of intra-thoracic desmoid tumors: case series and
      narrative review.
AB  - BACKGROUND: Primary intra-thoracic desmoids are exceedingly rare borderline
      tumors, with 34 reported cases in the English-language literature. The
      characteristic localized infiltrative growth and the high rate of recurrence can
      result in life-threatening conditions. Radical surgical resection is considered
      to be the primary treatment. Achieving negative surgical margins is a challenge.
      Cases with positive surgical margins are associated with a high rate of local
      recurrence; therefore, other multimodal approaches play a large role in their
      therapy. CASE REPORTS: The authors reviewed the relevant literature and presented
      examples of long-term follow-up of 3 intra-thoracic desmoid tumour patients,
      multidisciplinarily treated between 2000 and 2008. All reports of intra-thoracic
      desmoid tumors that the authors could find on PubMed or in the reference sections
      of these PubMed located articles were included using the search terms: intra
      thoracic, desmoid, aggressive fibromatoses. CONCLUSIONS: Because of the rarity of
      the disease and the heterogeneity of the cases, it is difficult to assess the
      importance of the information for everyday clinical practice. It does however
      provide a useful guide for reference.

PMID- 22367133
TI  - Takotsubo syndrome in a patient after renal transplantation.
AB  - BACKGROUND: Takotsubo syndrome (TTS) is a transient cardiomyopathy of unknown
      origin, clinically manifesting as acute coronary syndrome (ACS). This syndrome
      mainly occurs in postmenopausal women and has a temporary relationship with
      emotional or physical stress. CASE REPORT: TTS occurred in 46-year-old female
      patient on the first day after renal transplantation. The predominant symptoms
      were connected with ACS, performed with low grade troponin elevation and
      characteristic shape of left ventricle depicted in echocardiography. Taking into
      consideration the risk of the development of contrast-induced nephropathy,
      coronary angiography (CA) was delayed; myocardial perfusion scintigraphy and
      iodine-123 metaiodobenzylguanidine (123I-mIBG) myocardial uptake were performed
      to confirm the clinical suspicion. Myocardial perfusion scintigraphy (MPS)
      performed in rest condition showed normal perfusion but myocardial uptake of 123I
      mIBG was impaired. Within 6 months after surgery, full recovery of all
      biochemical and functional parameters of the left ventricle were observed. At
      that time CA was done, depicting normal coronary arteries. CONCLUSIONS: TTS could
      be diagnosed by the use of non-nephrotoxic tests - 123I-mIBG myocardial
      scintigraphy, MPS and echocardiography.

PMID- 22367134
TI  - Statistical agreement of left ventricle measurements using cardiac magnetic
      resonance and 2D echocardiography in ischemic heart failure.
AB  - BACKGROUND: The aim of this study was to compare cardiac magnetic resonance
      imaging (CMR) with 2-dimensional echocardiography (2D echo) in the assessment of
      left ventricle (LV) function parameters and mass in patients with ischemic heart
      disease and severely depressed LV function. Although 2D echo is commonly used to
      assess LV indices, CMR is the state-of-the-art technique. Agreement between these
      2 methods in these patients has not been well established. MATERIAL/METHODS: LV
      indexed end systolic and diastolic volumes (EDVi and ESVi), indexed mass (LVMi)
      and ejection fraction (EF) were assessed in 67 patients (12 women), using 2D echo
      and CMR. RESULTS: According to statistical analysis (Bland-Altman), 2D echo
      underestimated LV EDV and ESV and overestimated EF and LVMi compared to CMR. The
      highest correlation between 2D echo and CMR was found for EDVi (R2=0.73,
      p<0.0001) and ESVi (R2=0.69, p<0.0001) and the lowest for EF (R2=0.21, p=0.001)
      and LVMi (R2=0.20, p=0.002). The maximal differences between 2D echo and CMR were
      found for highest mesurements of LV volumes and mass, and for lowest EF values.
      CONCLUSIONS: There is moderate to strong correlation between CMR and 2D echo in
      the assessment of LV function parameters and mass in patients with ischemic heart
      failure. Between-method agreement depends on the degree of LV dysfunction. The
      results of assessment of the severely damaged LV obtained by the use of 2D echo
      should be interpreted with caution.

PMID- 22367135
TI  - The relationship between family socioeconomic condition and childhood injury
      frequency in selected locations in the Czech Republic.
AB  - BACKGROUND: Childhood injury rates are monitored worldwide because they markedly
      affect morbidity and mortality of children. There are numerous works that point
      out the relationship between family socioeconomic status and injuries, where
      lower socioeconomic levels are linked to higher numbers of injuries.
      MATERIAL/METHODS: The goal of this work was to evaluate the relationship between
      family socioeconomic status and childhood injuries in the Czech Republic. The
      research was carried out between 1/7/2009 and 31/12/2010. A 2-part questionnaire
      was used to gather information. The first part, "Injury/poisoning of children,"
      included information on the injury itself; the second part, "Family
      functionality," concerned family socioeconomic situations. We collected a total
      of 874 questionnaires in the South-Bohemian region and 132 questionnaires from a
      selected county in the North-Bohemian region. A database identical with the
      questionnaire assignment was established, comprising all the data accumulated.
      RESULTS: The injury rate in families living in poor socioeconomic situations in
      locality 8 was statistically significantly higher compared to families in good
      socioeconomic situations. The number of home injuries was 205. Families with
      incomes that were twice the subsistence level had more child protective measures
      in their households. There was a statistically significant relationship between
      the number of child protective measures and injury frequency in families.
      Children in families having higher incomes (twice that of subsistence level) were
      more likely to suffer injuries related to organized sports as compared to those
      in families having lower incomes. CONCLUSIONS: The literature and research data
      show that preventive programs have the largest effect on reduction in childhood
      morbidity and mortality with respect to injuries.

PMID- 22367136
TI  - Anti-HCV prevalence in the general population of Lithuania.
AB  - BACKGROUND: The aim of this study was to assess risk factors for HCV acquisition
      and prevalence of anti-HCV in the general population of Lithuania.
      MATERIAL/METHODS: The study enrolled 1528 randomly selected adults from the 5
      biggest cities of Lithuania and its rural regions. Screening for anti-HCV was
      performed by analysis of peripheral capillary blood with lateral flow
      immunochromatography and confirmation of positive cases by peripheral venous
      blood testing with 2-step chemiluminescent microparticle immunoassay. RESULTS:
      Anti-HCV prevalence in Lithuania is 2.78% and according to the standard European
      population the adjusted anti-HCV rate is 2.85%. It is more prevalent among men
      (crude rates: 4.02% males vs. 1.49% females, p=.0030) and this does not depend on
      age. Vilnius and Kaunas regions have higher infection rates than smaller rural
      regions (2.92% and 3.01% vs. 2.24%, 0.74% and 1.35%). Nowadays among our
      population HCV infection spreads mainly via intravenous drug use (OR=42.5,
      p<.0001). HCV transmission occurs through blood transfusions (OR=6.4, p=.0002),
      tooth removal (OR=4.1, p=.0048), childbirth (OR=5.0, p=.0224), multiple and a
      long-term hospitalization (OR=3.0, p=.0064), tattooing (OR=4.4, p=.0013), open
      traumas (OR=3.7, p=.0009) and intrafamilially (OR=11.3, p=.0002). CONCLUSIONS:
      2.78% of the population is anti-HCV-positive. The anti-HCV rate is higher in
      Vilnius and Kaunas in comparison with other regions. HCV spreads mainly through
      intravenous drug use, but intrafamilial and some nosocomial routes are also
      important. The anti-HCV prevalence did not depend on age. Despite active
      prevention of nosocomial HCV transmission, the incidence of HCV infection does
      not decrease due to virus spread mostly in "trusted networks" of intravenous drug
      users.

PMID- 22367137
TI  - Association between sleep quality and arterial blood pressure among Chinese
      nonagenarians/centenarians.
AB  - BACKGROUND: There is association between sleep quality and arterial blood
      pressure, but it is still unclear if the association also exists in the very
      elderly. We examined the individual association between sleep quality and
      arterial blood pressure among the very elderly. MATERIAL/METHODS: The present
      study analyzed data from a survey that was conducted on all residents aged 90
      years or older in a district with 2,311,709 inhabitants in 2005. Sleep quality
      was measured using The Pittsburgh Sleep Quality Index (PSQI). RESULTS: The
      subjects included in the statistical analysis were 216 men and 444 women. There
      were no significant differences in sleep quality scores, sleep latency, and sleep
      efficiency percentage and prevalence of poor sleep quality between subjects with
      and without hypertension. None of the differences in systolic blood pressure,
      diastolic blood pressure, and prevalence of hypertension, systolic hypertension
      and diastolic hypertension among subjects with well, fairly and poor sleep
      quality were significant. Multiple logistic regressions showed that unadjusted
      and adjusted Odds Ratio (ORs) of poor sleep quality for increased risk for
      hypertension were significant. CONCLUSIONS: Among very elderly subjects, there
      was no association between sleep quality and arterial blood pressure.

PMID- 22367138
TI  - Serum-soluble TRAIL levels in patients with severe persistent allergic asthma:
      its relation to omalizumab treatment.
AB  - BACKGROUND: In this study we compare the Omalizumab treatment modality in the
      dynamics of cell apoptosis regulating molecules in both severe persistent asthma
      patients who had no other any allergic disease, newly diagnosed patients with
      allergic asthma, and healthy volunteers. MATERIAL/METHODS: Severe persistent
      allergic asthma patients were subjected to measurement of serum soluble TRAIL
      (TNF-related apoptosis-inducing ligand) levels during the active disease phase
      and the stable phase which occurred 4 months after Omalizumab treatment. Serum
      sTRAIL concentrations were measured by a solid phase sandwich enzyme-linked
      immunosorbent assay. Concentration levels were compared with those of age- and
      sex-matched newly diagnosed patients with allergic asthma, and healthy controls.
      All assays were carried out in duplicate. Total serum IgE levels, antinuclear
      antibody (ANA), rheumatoid factor (RF), hepatitis markers, C3, C4 and eosinophil
      levels were evaluated in all patients. RESULTS: ANA, RF, hepatitis markers were
      negative in all patients. Complement 3 and 4 levels were normal in all patients.
      Prick tests in all patients were detected in mite and grass allergy. These
      results correlated with specific IgE. There were no differences between the
      healthy controls, newly diagnosed allergic asthma patients, and non-treated
      severe persistent allergic asthma patients during the active phase.
      Interestingly, the levels in variances of the patients who had the effective
      omalizumab treatment were significantly lower than the healthy controls, while
      the mean values were not statistically significant. CONCLUSIONS: Our study gives
      a different perspective on severe persistent allergic asthma and omalizumab
      treatment efficacy at the cell apoptosis-linked step by the serum sTRAIL levels.

PMID- 22367139
TI  - Ultrastructural changes in the cemento-enamel junction after vital tooth
      bleaching with fluoride and fluoride-free agents - a pilot study.
AB  - BACKGROUND: The impact of bleaching on the cemento-enamel junction (CEJ) is not
      well known. Due to frequent sensitivity of the cervical region of teeth after the
      vital bleaching, the aim of the present study was to evaluate the morphological
      features of the CEJ of human teeth after application of fluoridated and fluoride
      free bleaching agents, as well as post-bleaching fluoridation treatment, by
      scanning electron microscopy (SEM) analysis. MATERIAL/METHODS: Thirty-five
      extracted permanent human teeth were longitudinally cut, yielding 70 specimens.
      Thirty specimens were randomly divided into the 3 experimental groups, and 20
      specimens, were used as (2) control groups, each: negative (untreated) control
      group; positive control group treated with 35% hydrogen peroxide; experimental
      group 1, bleaching with 10% carbamide peroxide (CP); experimental group 2,
      treatment with a mixture of 10% CP and fluoride; and experimental group 3,
      treatment with 10% CP and 2% sodium fluoride gel applied 30 minutes after
      bleaching. Experimental groups were treated 8 h per day for 14 days. The samples
      were examined by SEM. RESULTS: The bleaching materials tested caused
      morphological changes to the surface of the CEJ. There was a statistically
      significant difference between experimental groups (Kruskal Wallis Test chi
      square=11,668; p<0.005). Mean value of experimental group 2 scores showed
      statistically significant difference from groups 1 and 3. CONCLUSIONS: Bleaching
      gel with fluorides does not significantly change morphological appearance of the
      CEJ and represents a better choice than the hard tissue fluoridation process
      after bleaching.

PMID- 22367140
TI  - HIV infections in otolaryngology.
AB  - HIV (human immunodeficiency virus) infection may produce no clinical symptoms for
      10 years on average. However, after many years of infection most people develop
      symptoms that indicate progression of the disease. There are no regular
      characteristic symptoms or early stage, and no logical sequence of AIDS indicator
      disorders has been observed. People who are not aware of the infection are
      referred to physicians of various specializations, including otolaryngologists.
      It is on their knowledge about HIV infections, among other factors, that early
      diagnosis of the disease depends. Appropriate and quick introduction of anti
      retroviral drugs may let a person with HIV live decades longer.

PMID- 22367142
TI  - Targeting mitochondrial biogenesis for promoting health.
AB  - Mitochondrial biogenesis is a key physiological process that is required for
      normal growth and development and for maintenance of ongoing cellular energy
      requirements during aging. Of equivalent and or greater importance is the
      regulated enhancement of mitochondrial biogenesis upon physiological demand
      coupled to multiple cellular insults. Basically, cellular survival mechanisms
      following a variety of disease-related pathophysiological insults are entrained
      by convergent mechanisms designed to regain homeostatic control of mitochondrial
      biogenesis. Recent molecular studies represent a clearly defined approach to
      maximize normative cellular expression of mitochondrial biogenesis for
      maintenance of cellular energy requirements and as an anti-aging strategy in
      healthy human populations. This report focuses on mitochondrial transcription
      factor A, peroxisome proliferator-activated receptor gamma coactivator 1-alpha,
      PINK1 and Parkin. Designing agents to target mitochondrial function represents a
      compelling therapeutic strategy for enhancement of cellular expression of
      mitochondrial biogenesis in diverse human populations afflicted with metabolic,
      degenerative, neurodegenerative, and metastatic diseases.<br />

PMID- 22367143
TI  - Types of injuries among Polish soldiers and civilian staff in the 7th, 8th, 9th
      and 10th rotation of the Afghan stabilization mission.
AB  - BACKGROUND: The Afghan military theatre is specifically marked by guerilla
      operations and massive use of IEDs (improvised explosive devices) that pose new
      types of threats for their victims. At the same time, the relevant literature
      contains only a single, fragmentary analysis on injuries suffered by soldiers
      serving in the Afghan mission. MATERIAL/METHODS: This is a review of medical
      reports of the Polish Military Contingent deployed within Operation Enduring
      Freedom, from 1 January 2010 to 31 December 2011; the analysis includes all cases
      of combat and non-combat injuries in terms of their causes. RESULTS: In the
      period under analysis, 380 Polish soldiers were reported injured; 87.1% of cases
      were combat and 12.9% non-combat injuries. The structure of injuries caused as a
      result of IED explosions was dominated by multiple limb injuries, associated most
      frequently with severe body cavities/spine injuries. In the case of other
      incidents, both combat and non-combat, the predominant consequences were single
      and, most commonly, less severe injuries. The average number of injuries suffered
      from IED attacks (3.37) was significantly higher than the number of injuries from
      other attacks (1.16), and higher than the number of non-combat injuries (1.43).
      CONCLUSIONS: IED attacks pose a serious medical problem, considering their high
      number and the severity of injuries they cause.

PMID- 22367145
TI  - [Cognitive/affective processes, social interaction and social structure].
AB  - Research on brain and structural analysis are overlapping but developed most
      often in independent ways. Here we consider biological mechanisms and
      environmental pressures for survival as simultaneously creating a gradual
      intersection of these various registers and changes in collaborative social
      interaction and communicative skills. We consider the ways humans have learned to
      characterize their brain life often depend on unexamined "representational
      redescriptions" that facilitate the depiction of practices.

PMID- 22367141
TI  - MicroRNA and its roles in esophageal cancer.
AB  - Esophageal cancer is the eighth most common cancer and causes the sixth highest
      cancer-related mortality worldwide. The 5-year survival of patients suffering
      from esophageal cancer in either advanced stage or metastasis is less than 20%.
      MicroRNAs are small, well conserved, non-coding RNA molecules that either repress
      translation or promote mRNA degradation based on the degree of complementary
      between miRNAs and mRNAs. Based on biogenesis and function of microRNAs, specific
      microRNA profiles, either from cancerous tissues or serum, were able to serve as
      diagnostic and prognostic biomarkers of esophageal cancer and predicted the
      effectiveness of surgery and chemoradiotherapy. MicroRNAs could also influence
      the biological behaviors of esophageal cancer cells, such as cellular
      proliferation, apoptosis, invasion and metastasis. MicroRNAs were also associated
      with multi-drug resistance of esophageal cancer. Further studies on the roles of
      microRNAs in esophageal cancer would provide a strategy to prevent and treat
      esophageal cancer, and reverse multi-drug resistance of esophageal cancer.

PMID- 22367146
TI  - [Where are we in general sociology ?].
AB  - Over the last two decades, history and social sciences have experienced a kind of
      merging, and a vast number of specialized domains have emerged. Yet the durkheim 
      ian register of "general sociology" seems somehow neglected. Firstly, this
      article analyzes the reasons for this neglect, and secondly, it indicates how,
      through a long-term reflexivity, one can formulate a new agenda for general
      sociology.

PMID- 22367152
TI  - Meeting the health care needs of LGBT patients.

PMID- 22367153
TI  - Using Diffusion of Innovations Theory to implement the confusion assessment
      method for the intensive care unit.
AB  - Routine screening of mechanically ventilated patients for delirium is essential
      for prompt recognition and management; however, this represents a change in
      practice. Rogers' Diffusion of Innovations Theory can be useful as a strategy to
      facilitate adoption of a practice change. This case study describes the
      effectiveness of identifying barriers to a change in practice and developing
      strategies, specific to Rogers' innovation decision process, for implementing the
      Confusion Assessment Method for the intensive care unit.

PMID- 22367154
TI  - Allergic contact dermatitis caused by metals in blackboard chalk: a case report.

PMID- 22367155
TI  - Cross-cultural differences in meter perception.
AB  - We examined the influence of incidental exposure to varied metrical patterns from
      different musical cultures on the perception of complex metrical structures from
      an unfamiliar musical culture. Adults who were familiar with Western music only
      (i.e., simple meters) and those who also had limited familiarity with non-Western
      music were tested on their perception of metrical organization in unfamiliar
      (Turkish) music with simple and complex meters. Adults who were familiar with
      Western music detected meter-violating changes in Turkish music with simple meter
      but not in Turkish music with complex meter. Adults with some exposure to non
      Western music that was unmetered or metrically complex detected meter-violating
      changes in Turkish music with both simple and complex meters, but they performed
      better on patterns with a simple meter. The implication is that familiarity with
      varied metrical structures, including those with a non-isochronous tactus,
      enhances sensitivity to the metrical organization of unfamiliar music.

PMID- 22367156
TI  - Tool-use in the brown bear (Ursus arctos).
AB  - This is the first report of tool-using behaviour in a wild brown bear (Ursus
      arctos). Whereas the use of tools is comparatively common among primates and has
      also been documented in several species of birds, fishes and invertebrates, tool
      using behaviours have so far been observed in only four species of non-primate
      mammal. The observation was made and photographed while studying the behaviour of
      a subadult brown bear in south-eastern Alaska. The animal repeatedly picked up
      barnacle-encrusted rocks in shallow water, manipulated and re-oriented them in
      its forepaws, and used them to rub its neck and muzzle. The behaviour probably
      served to relieve irritated skin or to remove food-remains from the fur. Bears
      habitually rub against stationary objects and overturn rocks and boulders during
      foraging and such rubbing behaviour could have been transferred to a freely
      movable object to classify as tool-use. The bear exhibited considerable motor
      skills when manipulating the rocks, which clearly shows that these animals
      possess the advanced motor learning necessary for tool-use. Advanced spatial
      cognition and motor skills for object manipulation during feeding and tool-use
      provide a possible explanation for why bears have the largest brains relative to
      body size of all carnivores. Systematic research into the cognitive abilities of
      bears, both in captivity and in the wild, is clearly warranted to fully
      understand their motor-learning skills and physical intelligence related to tool
      use and other object manipulation tasks.

PMID- 22367157
TI  - Prognostic value of preoperative coronary computed tomography angiography in
      patients treated by orthotopic liver transplantation.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of 64-slice
      coronary computed tomography (CT) angiography in patients treated by orthotopic
      liver transplantation, and to compare prognostic values of CT angiography and
      dobutamine stress echocardiography in the same population. METHODS: Eighty-two
      consecutive patients, without known coronary artery disease, who underwent
      orthotopic liver transplantation, were included in this study. A CT angiography
      was performed along with usual explorations including dobutamine stress
      echography. A one-year minimal follow-up was performed to seek cardiac events.
      RESULTS: Fifty-two (65.8%) patients underwent a CT angiography. Thirty-seven
      (71%) were totally normal or showed nonobstructive coronary plaque, six (12%)
      showed at least one obstructive coronary plaque greater than 50%. Nine (17%) of
      the examined patients had at least one nonassessable segment. A total of six
      (7.6%) major cardiac events occurred in a mean-time follow-up of 17.8 +/- 12.7
      months. CONCLUSION: CT angiography that is normal or with a nonobstructive
      coronary plaque has a negative predicting value of 95% [0.82-0.99] for major
      cardiac adverse events, and of 100% [0.91-1] for clinical coronary events in
      patients undergoing orthotopic liver transplantation. The prognostic value of CT
      angiography was comparable with that of dobutamine stress echography.

PMID- 22367159
TI  - Preparation and characterization of malonic acid cross-linked chitosan and
      collagen 3D scaffolds: an approach on non-covalent interactions.
AB  - The present study emphasizes the influence of non-covalent interactions on the
      mechanical and thermal properties of the scaffolds of chitosan/collagen origin.
      Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross
      linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v)
      and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and
      characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile
      strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence
      of non-covalent interaction between MA and chitosan/collagen, which offered
      flexibility and high strength to the scaffolds suitable for tissue engineering
      research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility
      nature of the scaffolds. Docking simulation study further supports the
      intermolecular hydrogen bonding interactions between MA and chitosan/collagen.

PMID- 22367161
TI  - Evolution and effectiveness of palliative care.
AB  - OBJECTIVE: : What is the evidence for the effectiveness of palliative medicine?
      METHOD: : A search of the PubMed database for clinical trials using search terms
      "Palliative Care" or "Palliative Medicine" or "Hospice" or "end of life" and
      "effectiveness" was conducted, and 63 articles were returned. Of these, 10 were
      related to outcomes of interest related to components of palliative medicine such
      as quality of life, length of life, or healthcare utilization. None were
      randomized, controlled trials looking at a global measure of effectiveness of
      palliative medicine. Consequently, additional searches using Google and Google
      Scholar, and searching bibliographies of published articles and presentations,
      were conducted. RESULTS: : There were not enough studies with which to perform a
      structured review. The findings from single trials of satisfactory methodological
      quality are summarized and presented. CONCLUSION: : Palliative care has been
      proven to be more effective than standard approaches to care. The thrust of
      research must now turn to ways to ensure that palliative care is part of standard
      care.

PMID- 22367165
TI  - Palliative care, geriatric psychiatry, and you.

PMID- 22367162
TI  - Sleep quality and its association with delirium among veterans enrolled in
      hospice.
AB  - OBJECTIVES: : The objectives of this study were to describe sleep quality and
      evaluate the association of sleep quality with delirium onset among patients
      enrolled in hospice. DESIGN: : The study utilized secondary data from a
      prospective, observational, longitudinal study. SETTING: : Veterans enrolled in
      hospice were recruited from the Portland Veterans Affairs Medical Center,
      Portland, Oregon. PARTICIPANTS: : The cohort consisted of 105 patients, of whom
      73% had at least one sleep measurement. MEASUREMENTS: : Sleep quality was
      measured with the Pittsburgh Sleep Quality Index. Delirium was measured with the
      Confusion Assessment Method. Other important variables were recorded from the
      medical record and/or longitudinal interviews with patients and their caregivers.
      Cox regression was used to estimate hazard ratios (HRs) to measure the
      association between sleep quality and delirium onset. RESULTS: : Of the patients
      who could be assessed, 44% had poor average sleep quality and 58% reported at
      least one episode of poor sleep. Overall, sleep quality did not appear to worsen
      as patients neared death although an increasing number of patients were unable to
      report on sleep quality. Poor sleep quality was associated with an increased risk
      of developing delirium, with an HR of 2.37 (95% CI: 1.50-3.74), for every one
      point worsening in the sleep quality score on a 4-point scale. CONCLUSIONS: :
      Poor sleep quality was common among Veteran patients enrolled in hospice. These
      findings may help guide decision making between clinicians, patients, and
      families regarding the likely impact of sleep disturbance and may help identify
      patients at higher risk of developing delirium.

PMID- 22367166
TI  - Effects of Scrophularia extracts on tumor cell proliferation, death and
      intravasation through lymphoendothelial cell barriers.
AB  - Different studies describe the anti-inflammatory effects of Scrophularia species,
      a medicinal plant widely used in folk medicine since ancient times. As knowledge
      regarding the anti-neoplastic properties of this species is rather limited, we
      investigated the influence of methanol extracts of different Scrophularia species
      on cell proliferation, cell death, and tumour cell intravasation through the
      lymph endothelial barrier. HL-60 leukaemia cells were treated with methanol
      extracts of different Scrophularia species leading to strong growth inhibition
      and high cell death rates. The expression of cell cycle regulators, oncogenes and
      cell death inducers was determined by Western blot analysis. Furthermore the
      effect of S. lucida was studied in an NF-kappaB reporter assay, and in a novel
      assay measuring 'circular chemo-repellent-induced defects' (CCID) in lymph
      endothelial monolayers that were induced by MCF-7 breast cancer spheroids.
      Methanol extracts of Scrophularia species exhibited strong anti-proliferative
      properties. S. floribunda extract inhibited G2/M- and later on S-phase and S.
      lucida inhibited S-phase and in both cases this was associated with the down
      regulation of c-Myc expression. Extracts of S. floribunda and S. lucida led to
      necrosis and apoptosis, respectively. Furthermore, S. lucida, but not S.
      floribunda, effectively attenuated tumour cell intravasation through lymph
      endothelial cell monolayers, which correlated with the inhibition of NF-kappaB.
      S. lucida exhibited promising anti-neoplastic effects and this was most likely
      due to the down-regulation of various cell cycle regulators, proto-oncogenes and
      NF-kappaB and the activation of caspase-3.

PMID- 22367167
TI  - 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of
      working memory, recognition memory and aversive learning in mice.
AB  - RATIONALE: Blockade of 5-HT6 receptors (5-HT6R) is known to improve cognitive
      performances in the rodent. This improvement has been hypothesized to be the
      result, at least in part, of a modulation of the cholinergic neurotransmission.
      OBJECTIVE: We assessed the effects of 5-HT6R blockade on selected types of memory
      relevant to functional deficits of ageing and neurodegenerative diseases, in mice
      that present a scopolamine-induced cholinergic disruption of memory. METHOD:
      Following the selection of an adequate dose of scopolamine to induce cognitive
      deficits, we have studied the effects of the selective 5-HT6R antagonist SB
      271046, alone or in combination with scopolamine, on working memory (spontaneous
      alternation task in the T-maze), recognition memory (place recognition) and
      aversive learning (passive avoidance). RESULTS: SB-271046 alone failed to affect
      working memory, recognition memory and aversive learning performances. In
      contrast, SB-271046 was able to reverse the scopolamine-induced deficits in
      working memory (only at 30 mg kg-1) and those of acquisition and retrieval of
      aversive learning (dose-dependent effect); scopolamine-induced deficits in
      episodic-like memory (acquisition and retrieval) were partially counteracted by 5
      HT6R blockade. CONCLUSION: The modulation between 5-HT6R and the cholinergic
      system appears to be predominant for working memory and aversive learning, but
      not for other types of memory (i.e. episodic-like memory). Interactions between 5
      HT6R and alternative neurotransmission systems (i.e. glutamatergic system) should
      be further studied. The respective involvement of these interactions in the
      memory disorders related to ageing and neurodegenerative diseases is of pivotal
      importance regarding the possible use of 5-HT6R antagonists in the treatment of
      memory disorders in humans.

PMID- 22367169
TI  - The uncertainty of UTCI due to uncertainties in the determination of radiation
      fluxes derived from numerical weather prediction and regional climate model
      simulations.
AB  - In this study we examine the determination accuracy of both the mean radiant
      temperature (Tmrt) and the Universal Thermal Climate Index (UTCI) within the
      scope of numerical weather prediction (NWP), and global (GCM) and regional (RCM)
      climate model simulations. First, Tmrt is determined and the so-called UTCI-Fiala
      model is then used for the calculation of UTCI. Taking into account the
      uncertainties of NWP model (among others the HIgh Resolution Limited Area Model
      HIRLAM) output (temperature, downwelling short-wave and long-wave radiation)
      stated in the literature, we simulate and discuss the uncertainties of Tmrt and
      UTCI at three stations in different climatic regions of Europe. The results show
      that highest negative (positive) differences to reference cases (under assumed
      clear-sky conditions) of up to -21 degrees C (9 degrees C) for Tmrt and up to -6
      degrees C (3.5 degrees C) for UTCI occur in summer (winter) due to cloudiness. In
      a second step, the uncertainties of RCM simulations are analyzed: three RCMs,
      namely ALADIN (Aire Limitee Adaptation dynamique Developpement InterNational),
      RegCM (REGional Climate Model) and REMO (REgional MOdel) are nested into GCMs and
      used for the prediction of temperature and radiation fluxes in order to estimate
      Tmrt and UTCI. The inter-comparison of RCM output for the three selected
      locations shows that biases between 0.0 and +/-17.7 degrees C (between 0.0 and +/
      13.3 degrees C) for Tmrt (UTCI), and RMSE between +/-0.5 and +/-17.8 degrees C
      (between +/-0.8 and +/-13.4 degrees C) for Tmrt (UTCI) may be expected. In
      general the study shows that uncertainties of UTCI, due to uncertainties arising
      from calculations of radiation fluxes (based on NWP models) required for the
      prediction of Tmrt, are well below +/-2 degrees C for clear-sky cases. However,
      significant higher uncertainties in UTCI of up to +/-6 degrees C are found,
      especially when prediction of cloudiness is wrong.

PMID- 22367168
TI  - Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice.
AB  - RATIONALE: Several studies suggest a role for neuropeptide Y (NPY) in addiction
      to drugs of abuse, including cocaine. However, the NPY receptors mediating
      addiction-related effects remain to be determined. OBJECTIVES: To explore the
      potential role of Y5 NPY receptors in cocaine-induced behavioural effects.
      METHODS: The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in
      two models of cocaine addiction-related behaviour: acute self-administration and
      cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism
      on cocaine-induced c-fos expression and extracellular dopamine with microdialysis
      as well as dopamine transporter-mediated uptake of dopamine in vitro.
      Immunocytochemistry was used to determine whether dopamine neurons express Y5
      like immunoreactivity. RESULTS: In self-administration, L-152,804 prominently
      decreased nose-poking for the peak dose of cocaine and shifted the dose-response
      curve for cocaine downward. Y5-KO mice also showed modestly attenuated self
      administration. Cocaine-induced hyperactivity was attenuated by L-152,804 and in
      Y5-KO mice. Cocaine failed to increase c-fos expression in the nucleus accumbens
      and striatum of L-152,804-treated mice, indicating that the Y5 antagonist could
      act by influencing neural activity in these regions. Accordingly, the cocaine
      induced increase in accumbal extracellular dopamine was attenuated by L-152,804
      and in Y5-KO mice, suggesting that Y5 antagonism influences cocaine-induced
      behaviour by regulating dopamine. Consistent with this concept, dopamine neurons
      in the ventral tegmental area appeared to contain Y5 receptors. In contrast,
      neither L-152,804 nor NPY influenced dopamine transporter-mediated dopamine
      uptake. CONCLUSIONS: The present data indicate that Y5 antagonism may attenuate
      cocaine-induced behavioural effects, suggesting that Y5 receptors could be a
      potential therapeutic target in cocaine addiction.

PMID- 22367170
TI  - Adult patients with sporadic polycystic kidney disease: the importance of
      screening for mutations in the PKD1 and PKD2 genes.
AB  - BACKGROUND: ADPKD is one of the most common inherited disorders, with high risk
      for end-stage renal disease. Numerous patients, however, have no relatives in
      whom this disorder is known and are unsure whether they may transmit the disease
      to their offsprings. The aim of this study was to evaluate whether germline
      mutation analysis adds substantial information to clinical symptoms for diagnosis
      of ADPKD in these patients. METHODS: Clinical data included renal function and
      presence of liver or pancreas cysts, heart valve insufficiency, intracranial
      aneurysms, colonic diverticles, and abdominal hernias. Family history was
      evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes
      was performed for intragenic mutations and for large deletions. RESULTS: A total
      of 324 adult patients with ADPKD including 30 patients without a family history
      of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and
      PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and
      intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal
      involvement. Compared to the 294 patients with familial ADPKD, the clinical
      characteristics and the age at the start of dialysis were similar in those with
      sporadic ADPKD. CONCLUSION: The clinical characteristics of patients with
      sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked
      because of the absence of a family history. Molecular genetic screening for
      germline mutations in both PKD1 and PKD2 genes is essential for the definitive
      diagnosis of ADPKD.

PMID- 22367171
TI  - Catastrophic paradoxical embolus after hemodialysis access thrombectomy in a
      patient with a patent foramen ovale.
AB  - We present the first case of documented clot in-transit through a patent foramen
      ovale (PFO), caused by mechanical thrombectomy of a clotted AV fistula. Embolus
      after access thrombectomy is a rare, but known complication of the procedure.
      Paradoxical embolus is likewise a rare consequence of a right-sided clot,
      embolising to the left-sided circulation in a patient with a PFO. Suspected
      embolus through a PFO after dialysis access thrombectomy has been reported, but
      no case has ever documented the clot in-transit through the PFO.

PMID- 22367172
TI  - Investigation of anal sphincter function following Mainz pouch type II urinary
      diversion after radical cystectomy.
AB  - PURPOSES: Our aim was to evaluate the anal sphincter function following
      cystectomy with urinary diversion of Mainz pouch II. METHODS: Seventy-six
      patients were involved in our survey, and the cohort was for two groups divided.
      The first group was a retrospective review of 40 patients with examination of the
      state of continence. Comparative examinations on anal sphincter function and the
      quality of life survey were carried out. The second group consisting of 15
      patients underwent a prospective investigation including rectal manometry in both
      the pre- and postoperative periods. Measurements of resting anal sphincter
      pressure (RASP), maximal anal closing pressure (MACP) and the function of the
      recto anal inhibitions reflex were taken. RESULTS: In the first part of our
      investigation, 80% of the patients were considered as continent. There were no
      significant differences observed between RASP values in the cases of continent as
      well as of incontinent patients (79.2 +/- 2 vs. 73.6 +/- 68.4 mmHg, p = 0-53);
      however, the MACP values of the continent patients were significantly higher
      (204.3 +/- 22.8 vs. 117.3 +/- 14 mmHg, p = 0.001). In the course of the second
      experiment, both the RASP (86.3 +/- 18.7 vs. 76.1 +/- 13.9 mmHg p = 0.0049) and
      the MACP (232.2 +/- 53.8 vs. 194.1 +/- 74.5 mmHg, p = 0.0054) were detected as
      decreasing in the case of the incontinent group. CONCLUSIONS: A decrease in
      rectal sphincter function is responsible for incontinence following Mainz pouch
      type II diversion, and this dysfunction can be correlated with the surgery.
      Ureterosigmoideostomy is therefore considered as a useful method of urinary
      diversion only in selected cases with proven good sphincter function.

PMID- 22367173
TI  - Age-related changes in Cngb1-X1 knockout mice: prolonged cone survival.
AB  - The rod photoreceptor cGMP-gated cation channel has an essential role in
      phototransduction functioning as the primary point for calcium and sodium entry
      into the rod outer segment. The channel consists of two subunits, alpha and beta.
      The alpha-subunit can function in isolation as an ion channel, and the beta
      subunit modulates channel activity and has a structural role. We previously
      reported that a mouse knockout (KO) of the beta-subunit and related glutamic acid
      rich proteins (GARPs) attenuates rod function and causes structural alterations
      and slowly progressive retinal degeneration. Here, we have extended our
      functional analyses of the KO mice evaluating rod and cone function using the
      electroretinogram in mice up to 4 months of age. Retinal stratification is
      preserved in the knockout mice at 3 months, and a significant number of cones
      remain up to 7 months based on PNA staining of cone sheaths. Electroretinography
      of KO mice at 1 month old revealed a diminished dark-adapted b-wave and normal
      light-adapted b-wave compared to wild-type mice. Over the next 3 months, both
      dark- and light-adapted b-wave amplitudes declined, but the reduction was greater
      for dark-adapted b-wave amplitudes. In one-month-old mice, the critical flicker
      frequency (CFF) was substantially lower for the KO mice at scotopic intensities,
      but normal at photopic intensities. CFF values remained stable in the KO mice as
      the b-wave amplitudes decreased with age. Declining b-wave amplitudes confirm an
      RP phenotype of rod followed by cone degeneration. Flicker responses show that
      the cone circuits function normally at threshold despite significant losses in
      the maximum light-adapted b-wave amplitude. These results confirm that rods are
      marginally functional in the absence of the beta-subunit and in addition show
      that CFF may be a more sensitive measure of remaining functional cone vision in
      animal models of RP undergoing progressive rod-cone degeneration.

PMID- 22367174
TI  - Pedophilia: a diagnosis in search of a disorder.
AB  - This article presents a critical review of the recent controversies concerning
      the diagnosis of pedophilia in the context of the preparation of the fifth
      edition of the DSM. The analysis focuses basically on the relationship between
      pedophilia and the current DSM-IV-TR's definition of mental disorder. Scholars
      appear not to share numerous basic assumptions ranging from their underlying
      ideas about what constitutes a mental disorder to the role of psychiatry in
      modern society, including irreconcilable theories about human sexuality, which
      interfere with reaching any kind of a consensus as to what the psychiatric status
      of pedophilia should be. It is questioned if the diagnosis of pedophilia
      contained in the DSM is more forensic than therapeutic, focusing rather on the
      dangers inherent in the condition of pedophilia (dangerous dysfunction) than on
      its negative effects for the subject (harmful dysfunction). The apparent
      necessity of the diagnosis of pedophilia in the DSM is supported, but the basis
      for this diagnosis is uncertain.

PMID- 22367175
TI  - Introduction to the special section "the puzzle of sexual orientation: what is it
      and how does it work?".

PMID- 22367176
TI  - Fhl1 as a downstream target of Wnt signaling to promote myogenesis of C2C12
      cells.
AB  - Previous studies have shown that Wnt signaling is involved in postnatal mammalian
      myogenesis; however, the downstream mechanism of Wnt signaling is not fully
      understood. This study reports that the murine four-and-a-half LIM domain 1
      (Fhl1) could be stimulated by beta-catenin or LiCl treatment to induce
      myogenesis. In contrast, knockdown of the Fhl1 gene expression in C2C12 cells led
      to reduced myotube formation. We also adopted reporter assays to demonstrate that
      either beta-catenin or LiCl significantly activated the Fhl1 promoter, which
      contains four putative consensus TCF/LEF binding sites. Mutations of two of these
      sites caused a significant decrease in promoter activity by luciferase reporter
      assay. Thus, we suggest that Wnt signaling induces muscle cell differentiation,
      at least partly, through Fhl1 activation.

PMID- 22367177
TI  - Corruption of human follicular B-lymphocyte trafficking by a B-cell superantigen.
AB  - Protein A (SpA) of Staphylococcus aureus is known to target the paratope of
      immunoglobulins expressing V(H)3 genes, and to delete marginal zone B cells and B
      1a in vivo. We have discovered that SpA endows S. aureus with the potential to
      subvert B-cell trafficking in the host. We found that SpA, whose Fc-binding site
      has been inactivated, binds essentially to naive B cells and induces a long
      lasting decrease in CXCR4 expression and in B-cell chemotaxis to CXCL12.
      Competition experiments indicated that SpA does not interfere with binding of
      CXCR4 ligands and does not directly bind to CXCR4. This conclusion is strongly
      supported by the inability of SpA to modulate clathrin-mediated CXCR4
      internalization, which contrasts with the potent effect of anti-immunoglobin M
      (IgM) antibodies. Microscopy and biochemical experiments confirmed that SpA binds
      to the surface IgM/IgD complex and induces its clathrin-dependent
      internalization. Concomitantly, the SpA-induced signaling leads to protein kinase
      C-dependent CXCR4 downmodulation, suggesting that SpA impairs the recycling of
      CXCR4, a postclathrin process that leads to either degradation into lysozomes or
      de novo expression at the cell surface. In addition to providing novel insight
      into disruption of B-cell trafficking by an infectious agent, our findings may
      have therapeutic implications. Because CXCR4 has been associated with cancer
      metastasis and with certain autoimmune diseases, SpA behaves as an evolutionary
      tailored highly specific, chemokine receptor inhibitor that may have value in
      addition to conventional cytotoxic therapy in patients with various malignancies
      and immune-mediated diseases.

PMID- 22367178
TI  - Rise of the sensors: nociception and pruritus.
AB  - Once there was a day when all type C nonmyelinated neurons were
      indistinguishable. That time of histologic analysis has passed, and we have
      entered an era of unparalleled technological insight into the mechanisms of pain
      and pruritus. Since the description of the capsaicin receptor, transient receptor
      protein vanilloid 1 (TRPV1), in 1997, we have seen the number of related sensor
      ion channels, G protein-coupled receptors, and signaling proteins explode.
      Specific nociceptive pathways have been identified based on their sensitivity to
      mechanical, heat, chemical, and cold stimuli. Pruritus is now recognized to have
      both histamine-sensitive and histamine-independent afferent arcs. Cross-talk
      between C-fibre systems and myelinated neural pathways has become more complex,
      but through complexity, a new reality of sensory coding is emerging. A multitude
      of novel therapeutics have been and are in planning and production stages. These
      will almost certainly revolutionize our understanding and treatment of pain and
      itch by the end of this decade.

PMID- 22367179
TI  - The prostate cancer bone marrow niche: more than just 'fertile soil'.
AB  - The hematopoietic stem cell (HSC) niche in the bone marrow has been studied
      extensively over the past few decades, yet the bone marrow microenvironment that
      supports the growth of metastatic prostate cancer (PCa) has only been recently
      considered to be a specialized 'niche' as well. New evidence supports the fact
      that disseminated tumor cells (DTCs) of PCa actually target the HSC niche,
      displace the occupant HSCs and take up residence in the pre-existing niche space.
      This review describes some of the evidence and mechanisms by which DTCs act as
      molecular parasites of the HSC niche. Furthermore, the interactions between DTCs,
      HSCs and the niche may provide new targets for niche-directed therapy, as well as
      insight into the perplexing clinical manifestations of metastatic PCa disease.

PMID- 22367180
TI  - Mobilisation of endothelial progenitor cells: one of the possible mechanisms
      involved in the chronic administration of melatonin preventing erectile
      dysfunction in diabetic rats.
AB  - Diabetes-induced oxidative stress plays a critical role in the mobilisation of
      endothelial progenitor cells (EPCs) from the bone marrow to the circulation. This
      study was designed to explore the effects of chronic melatonin administration on
      the promotion of the mobilisation of EPCs and on the preservation of erectile
      function in type I diabetic rats. Melatonin was administered to streptozotocin
      induced type I diabetic rats. EPCs levels were determined using flow cytometry.
      Oxidative stress in the bone marrow was indicated by the levels of superoxide
      dismutase and malondialdehyde. Erectile function was evaluated by measuring the
      intracavernous pressure during an electrostimulation of the cavernous nerve. The
      density of the endothelium and the proportions of smooth muscle and collagen in
      the corpus cavernosum were determined by immunohistochemistry. The administration
      of melatonin increased the superoxide dismutase level and decreased the
      malondialdehyde level in the bone marrow. This effect was accompanied by an
      increased level of circulating EPCs in the diabetic rats. The intracavernous
      pressure to mean arterial pressure ratio of the rats in the treatment group was
      significantly greater, compared with diabetic control rats. The histological
      analysis demonstrated an increase in the endothelial density of the corpus
      cavernosum after the administration of melatonin. However, melatonin treatment
      did not change the proportions of smooth muscle and collagen in the corpus
      cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial
      effect on preventing erectile dysfunction (ED) in type I diabetic rats. Promoting
      the mobilisation of EPCs is one of the possible mechanisms involved in the
      improvement of ED.

PMID- 22367181
TI  - Formalized prediction of clinically significant prostate cancer: is it possible?
AB  - Greater understanding of the biology and epidemiology of prostate cancer in the
      last several decades have led to significant advances in its management. Prostate
      cancer is now detected in greater numbers at lower stages of disease and is
      amenable to multiple forms of efficacious treatment. However, there is a lack of
      conclusive data demonstrating a definitive mortality benefit from this earlier
      diagnosis and treatment of prostate cancer. It is likely due to the treatment of
      a large proportion of indolent cancers that would have had little adverse impact
      on health or lifespan if left alone. Due to this overtreatment phenomenon, active
      surveillance with delayed intervention is gaining traction as a viable management
      approach in contemporary practice. The ability to distinguish clinically
      insignificant cancers from those with a high risk of progression and/or lethality
      is critical to the appropriate selection of patients for surveillance protocols
      versus immediate intervention. This chapter will review the ability of various
      prediction models, including risk groupings and nomograms, to predict indolent
      disease and determine their role in the contemporary management of clinically
      localized prostate cancer.

PMID- 22367182
TI  - Diffusion-weighted MR imaging of normal and abnormal scrotum: preliminary
      results.
AB  - Magnetic resonance (MR) imaging of the scrotum represents an important
      supplemental diagnostic tool in the evaluation of scrotal diseases. Diffusion
      weighted (DW) MR imaging is a developing technique, proved to improve tissue
      characterization. We evaluated the feasibility and diagnostic performance of DW
      MR imaging in the detection and characterization of scrotal lesions. We
      retrospectively evaluated 31 scrotal lesions (23 intratesticular and 8
      extratesticular) in 26 men. All MR examinations were performed on a 1.5-T unit,
      using a pelvic-phased array coil. DW sequences were obtained using a single shot,
      multislice spin echo planar diffusion pulse sequence and a b factor of 0 and 900
      s mm(-2). The DW MR characteristics and the apparent diffusion coefficient (ADC)
      values of normal scrotal contents and scrotal diseases were evaluated. Comparison
      between the ADC values of normal scrotum, benign lesions and scrotal malignancies
      was performed. The accuracy of conventional sequences, DW images alone and DW
      imaging combined with conventional images in differentiating benign from
      malignant scrotal lesions was calculated. The ADC values of testicular
      malignancies were different from those of normal testis and benign
      intratesticular lesions, and the ADC values of benign extratesticular lesions
      from those of normal epididymis (P<0.05). The overall accuracy of conventional
      imaging, DW imaging alone and DW MR combined with conventional sequences in the
      characterization of intratesticular lesions was 91%, 87% and 100%, respectively.
      Our findings suggest that DW MR imaging and ADC values may provide valuable
      information in the diagnosis and characterization of scrotal diseases.

PMID- 22367185
TI  - Time to raise awareness regarding complications of androgen deprivation therapy.

PMID- 22367186
TI  - Silencing TRPC1 expression inhibits invasion of CNE2 nasopharyngeal tumor cells.
AB  - The invasion and metastasis processes involved in nasopharyngeal carcinoma (NPC)
      remain enigmatic. Transient receptor potential channel-related protein 1 (TRPC1)
      is a cation channel involved in diverse cellular functions by precisely
      controlling Ca2+. The role of this unique TRPC member in nasopharyngeal
      malignancies has not yet been delineated. Here, we downregulated TRPC1 in CNE2
      cells by RNAi technology and by using 2-APB, an inhibitor of the inositol 1,4,5
      trisphosphate (IP3) receptor and of store-operated Ca2+ channel-mediated Ca2+
      entry. Both types of TRPC1 inhibition resulted in significantly attenuated
      adhesive and invasive abilities, suggesting that TRPC1 can modulate the
      metastasis of NPC. These findings support further investigation of the potential
      of TRPC1 as a novel therapeutic target for intervention in nasopharyngeal
      carcinoma.

PMID- 22367184
TI  - Muscle function, physical performance and body composition changes in men with
      prostate cancer undergoing androgen deprivation therapy.
AB  - Prostate cancer (PCa) is the most common visceral malignancy in men with androgen
      deprivation therapy (ADT) the preferred therapy to suppress testosterone
      production and hence tumor growth. Despite its effectiveness in lowering
      testosterone, ADT is associated with side effects including loss of muscle mass,
      diminished muscle strength, decrements in physical performance, earlier fatigue
      and declining quality of life. This review reports a survey of the literature
      with a focus on changes in muscle strength, physical function and body
      composition, due to short-term and long-term ADT. Studies in these areas are
      sparse, especially well-controlled, prospective randomized trials. Cross
      sectional and longitudinal data (up to 2 years) for men with PCa treated with ADT
      as well as patients with PCa not receiving ADT and age-matched healthy men are
      presented when available. Based on limited longitudinal data, the adverse effects
      of ADT on muscle function, physical performance and body composition occur
      shortly after the onset of ADT and tend to persist and worsen over time. Exercise
      training is a safe and effective intervention for mitigating these changes and
      initial guidelines for exercise program design for men with PCa have been
      published by the American College of Sports Medicine. Disparities in study
      duration, types of studies and other patient-specific variables such as time
      since diagnosis, cancer stage and comorbidities may all affect an understanding
      of the influence of ADT on health, physical performance and mortality.

PMID- 22367187
TI  - Eligibility criteria and psychological profiles in patient candidates for awake
      craniotomy:  a pilot study.
AB  - BACKGROUND: Although generally well tolerated, awake craniotomy is burdened by
      non-negligible failure rates. The aim of this pilot study was to verify the
      feasibility of a wider research scope to define objective criteria for patient
      exclusion and the risk of intraoperative mapping failures. METHODS: Twenty-one
      patients with brain tumors were subjected to a procedure in 3 steps:
      neuropsychological criteria for both cognition and language; psychological
      questionnaires for anxiety, attitude to pain and depression, and
      psychophysiological monitoring for the candidate's capacity for self-control; and
      an intraoperative interview for the patient's perception during awake procedure.
      Outcome measures were as follows: (1) patient compliance, defined as patient
      response to the intraoperative procedure and measured by psychological scale
      scores for fear and pain, and (2) failure, defined as the impossibility to
      complete brain mapping (minor) or conversion to general anesthesia (major). Data
      analysis included the description of preoperative and intraoperative assessments
      and their evaluation (Spearman rho test), and the prognostic factors for
      intraoperative compliance and procedure failure (Mann-Whitney test). RESULTS:
      Three patients were considered ineligible after the first step. In the remaining
      18, the responses of 10 patients fell within the normal range and 8 showed some
      degree of impairment on at least 1 preoperative evaluation, but not enough to be
      excluded from awake surgery. The data analysis also showed that fear of pain
      correlated with pain felt during the operation and preoperatively with depression
      and psychophysiological changes, the latter of which was associated with fear
      felt during craniotomy. Minor failures occurred in 2 patients. CONCLUSIONS: From
      these preliminary results, we observed that warning signs for minor failure were
      fear of pain and anxiety, as revealed by psychological questionnaire responses,
      and the incapability of self-control at psychophysiological monitoring. This
      assessment may serve to fit mapping modality to the single patient and to avoid
      complications.

PMID- 22367189
TI  - Awake craniotomy under xenon anesthesia:  first experience.

PMID- 22367190
TI  - Sensitive mapping of recombination hotspots using sequencing-based detection of
      ssDNA.
AB  - Meiotic DNA double-stranded breaks (DSBs) initiate genetic recombination in
      discrete areas of the genome called recombination hotspots. DSBs can be directly
      mapped using chromatin immunoprecipitation followed by sequencing (ChIP-seq).
      Nevertheless, the genome-wide mapping of recombination hotspots in mammals is
      still a challenge due to the low frequency of recombination, high heterogeneity
      of the germ cell population, and the relatively low efficiency of ChIP. To
      overcome these limitations we have developed a novel method--single-stranded DNA
      (ssDNA) sequencing (SSDS)--that specifically detects protein-bound single
      stranded DNA at DSB ends. SSDS comprises a computational framework for the
      specific detection of ssDNA-derived reads in a sequencing library and a new
      library preparation procedure for the enrichment of fragments originating from
      ssDNA. The use of our technique reduces the nonspecific double-stranded DNA
      (dsDNA) background >10-fold. Our method can be extended to other systems where
      the identification of ssDNA or DSBs is desired.

PMID- 22367183
TI  - Specific changes in the expression of imprinted genes in prostate cancer-
      implications for cancer progression and epigenetic regulation.
AB  - Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation,
      enhancer of zeste homologue 2 (EZH2) overexpression and altered patterns of
      histone modifications is associated with the progression of prostate cancer. DNA
      methylation, EZH2 and histone modifications also ensure the parental-specific
      monoallelic expression of at least 62 imprinted genes. Although it is therefore
      tempting to speculate that epigenetic dysregulation may extend to imprinted
      genes, expression changes in cancerous prostates are only well documented for
      insulin-like growth factor 2 (IGF2). A literature and database survey on
      imprinted genes in prostate cancer suggests that the expression of most imprinted
      genes remains unchanged despite global disturbances in epigenetic mechanisms.
      Instead, selective genetic and epigenetic changes appear to lead to the
      inactivation of a sub-network of imprinted genes, which might function in the
      prostate to limit cell growth induced via the PI3K/Akt pathway, modulate androgen
      responses and regulate differentiation. Whereas dysregulation of IGF2 may
      constitute an early change in prostate carcinogenesis, inactivation of this
      imprinted gene network is rather associated with cancer progression.

PMID- 22367192
TI  - Joint genotyping on the fly: identifying variation among a sequenced panel of
      inbred lines.
AB  - High-throughput sequencing is enabling remarkably deep surveys of genomic
      variation. It is now possible to completely sequence multiple individuals from a
      single species, yet the identification of variation among them remains an
      evolving computational challenge. This challenge is compounded for experimental
      organisms when strains are studied instead of individuals. In response, we
      present the Joint Genotyper for Inbred Lines (JGIL) as a method for obtaining
      genotypes and identifying variation among a large panel of inbred strains or
      lines. JGIL inputs the sequence reads from each line after their alignment to a
      common reference. Its probabilistic model includes site-specific parameters
      common to all lines that describe the frequency of nucleotides segregating in the
      population from which the inbred panel was derived. The distribution of line
      genotypes is conditional on these parameters and reflects the experimental
      design. Site-specific error probabilities, also common to all lines, parameterize
      the distribution of reads conditional on line genotype and realized coverage.
      Both sets of parameters are estimated per site from the aggregate read data, and
      posterior probabilities are calculated to decode the genotype of each line. We
      present an application of JGIL to 162 inbred Drosophila melanogaster lines from
      the Drosophila Genetic Reference Panel. We explore by simulation the effect of
      varying coverage, sequencing error, mapping error, and the number of lines. In
      doing so, we illustrate how JGIL is robust to moderate levels of error. Supported
      by these analyses, we advocate the importance of modeling the data and the
      experimental design when possible.

PMID- 22367191
TI  - Mouse endogenous retroviruses can trigger premature transcriptional termination
      at a distance.
AB  - Endogenous retrotransposons have caused extensive genomic variation within
      mammalian species, but the functional implications of such mobilization are
      mostly unknown. We mapped thousands of endogenous retrovirus (ERV) germline
      integrants in highly divergent, previously unsequenced mouse lineages,
      facilitating a comparison of gene expression in the presence or absence of local
      insertions. Polymorphic ERVs occur relatively infrequently in gene introns and
      are particularly depleted from genes involved in embryogenesis or that are highly
      expressed in embryonic stem cells. Their genomic distribution implies ongoing
      negative selection due to deleterious effects on gene expression and function. A
      polymorphic, intronic ERV at Slc15a2 triggers up to 49-fold increases in
      premature transcriptional termination and up to 39-fold reductions in full-length
      transcripts in adult mouse tissues, thereby disrupting protein expression and
      functional activity. Prematurely truncated transcripts also occur at Polr1a,
      Spon1, and up to ~5% of other genes when intronic ERV polymorphisms are present.
      Analysis of expression quantitative trait loci (eQTLs) in recombinant BxD mouse
      strains demonstrated very strong genetic associations between the polymorphic ERV
      in cis and disrupted transcript levels. Premature polyadenylation is triggered at
      genomic distances up to >12.5 kb upstream of the ERV, both in cis and between
      alleles. The parent of origin of the ERV is associated with variable expression
      of nonterminated transcripts and differential DNA methylation at its 5'-long
      terminal repeat. This study defines an unexpectedly strong functional impact of
      ERVs in disrupting gene transcription at a distance and demonstrates that ongoing
      retrotransposition can contribute significantly to natural phenotypic diversity.

PMID- 22367193
TI  - A single-dose placebo- and moxifloxacin-controlled study of the effects of
      temsirolimus on cardiac repolarization in healthy adults.
AB  - PURPOSE: Temsirolimus, a selective inhibitor of mammalian target of rapamycin, is
      an approved treatment for patients with advanced renal cell carcinoma (RCC). This
      study assessed the effect of intravenous (i.v.) temsirolimus 25 mg, the
      recommended dose for patients with RCC, on the corrected QT (QTc) interval.
      METHODS: This 3-period crossover study enrolled healthy subjects. In periods 1
      and 2, subjects received i.v. placebo either alone or with open-label oral
      moxifloxacin. In period 3, subjects received a single dose of temsirolimus 25 mg.
      The primary statistical objective was to estimate the effect of temsirolimus
      compared with placebo on change from time-matched baseline QTc at the end of
      infusion (0.5 h). Assay sensitivity was evaluated by the effect of moxifloxacin
      on change from time-matched baseline QTc compared with placebo. RESULTS: In
      total, 58 subjects were enrolled. Temsirolimus had no effect on QTc interval in
      the primary analysis. At 11 of 12 secondary time points, the upper bound for the
      temsirolimus QTc 90% confidence intervals for the time-matched change from
      baseline difference from placebo was <10 ms, with no evidence of QTc trends or
      relationship to concentrations of temsirolimus or its major metabolite,
      sirolimus. Moxifloxacin, the positive control, produced a significant increase in
      the QTc interval compared with placebo 0.5-4 h post-dose (P < 0.0001). No subject
      had a QTc interval exceeding 450 ms or a change from baseline of >30 ms.
      CONCLUSIONS: Therapeutic exposure to temsirolimus is not associated with
      clinically significant changes in QTc intervals in healthy adults.

PMID- 22367194
TI  - Biochemical characterization and N-terminomics analysis of leukolysin, the
      membrane-type 6 matrix metalloprotease (MMP25): chemokine and vimentin cleavages
      enhance cell migration and macrophage phagocytic activities.
AB  - The neutrophil-specific protease membrane-type 6 matrix metalloproteinase (MT6
      MMP)/MMP-25/leukolysin is implicated in multiple sclerosis and cancer yet remains
      poorly characterized. To characterize the biological roles of MT6-MMP, it is
      critical to identify its substrates for which only seven are currently known.
      Here, we biochemically characterized MT6-MMP, profiled its tissue inhibitor of
      metalloproteinase inhibitory spectrum, performed degradomics analyses, and
      screened 26 chemokines for cleavage using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. MT6-MMP
      processes seven each of the CXC and CC chemokine subfamilies. Notably, cleavage
      of the neutrophil chemoattractant CXCL5 activates the chemokine, thereby
      increasing its agonist activity, indicating a feed-forward mechanism for
      neutrophil recruitment. Likewise, cleavage also activated CCL15 and CCL23 to
      increase monocyte recruitment. Utilizing the proteomics approach proteomic
      identification of cleavage site specificity (PICS), we identified 286 peptidic
      cleavage sites spanning from P6 to P6' from which an unusual glutamate preference
      in P1 was identified. The degradomics screen terminal amine isotopic labeling of
      substrates (TAILS), which enriches for neo-N-terminal peptides of cleaved
      substrates, was used to identify 58 new native substrates in fibroblast
      secretomes after incubation with MT6-MMP. Vimentin, cystatin C, galectin-1, IGFBP
      7, and secreted protein, acidic and rich in cysteine (SPARC) were among those
      substrates we biochemically confirmed. An extracellular "moonlighting" form of
      vimentin is a chemoattractant for THP-1 cells, but MT6-MMP cleavage abolished
      monocyte recruitment. Unexpectedly, the MT6-MMP-cleaved vimentin potently
      stimulated phagocytosis, which was not a property of the full-length protein.
      Hence, MT6-MMP regulates neutrophil and monocyte chemotaxis and by generating
      "eat-me" signals upon vimentin cleavage potentially increases phagocytic removal
      of neutrophils to resolve inflammation.

PMID- 22367195
TI  - Interferon regulatory factor 1 transactivates expression of human DNA polymerase
      eta in response to carcinogen N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - DNA polymerase eta (Poleta) implements translesion DNA synthesis but has low
      fidelity in replication. We have previously shown that Poleta plays an important
      role in the genesis of nontargeted mutations at undamaged DNA sites in cells
      exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Here, we
      report that MNNG-induced Poleta expression in an interferon regulatory factor 1
      (IRF1)-dependent manner in human cells. Mutagenesis analysis showed that four
      critical residues (Arg-82, Cys-83, Asn-86, and Ser-87) located in the IRF family
      conserved DNA binding domain-helix alpha3 were involved in DNA binding and POLH
      transactivation by IRF1. Furthermore, Poleta up-regulation induced by IRF1 was
      responsible for the increase of mutation frequency in a SupF shuttle plasmid
      replicated in the MNNG-exposed cells. Interestingly, IRF1 was acetylated by the
      histone acetyltransferase CBP in these cells. Lys -> Arg substitution revealed
      that Lys-78 of helix alpha3 was the major acetylation site, and the IRF1-K78R
      mutation partially inhibited DNA binding and its transcriptional activity. Thus,
      we propose that IRF1 activation is responsible for MNNG-induced Poleta up
      regulation, which contributes to mutagenesis and ultimately carcinogenesis in
      cells.

PMID- 22367196
TI  - Genetic dissection of pyrimidine biosynthesis and salvage in Leishmania donovani.
AB  - Protozoan parasites of the Leishmania genus express the metabolic machinery to
      synthesize pyrimidine nucleotides via both de novo and salvage pathways. To
      evaluate the relative contributions of pyrimidine biosynthesis and salvage to
      pyrimidine homeostasis in both life cycle stages of Leishmania donovani,
      individual mutant lines deficient in either carbamoyl phosphate synthetase (CPS),
      the first enzyme in pyrimidine biosynthesis, uracil phosphoribosyltransferase
      (UPRT), a salvage enzyme, or both CPS and UPRT were constructed. The Deltacps
      lesion conferred pyrimidine auxotrophy and a growth requirement for medium
      supplementation with one of a plethora of pyrimidine nucleosides or nucleobases,
      although only dihydroorotate or orotate could circumvent the pyrimidine
      auxotrophy of the Deltacps/Deltauprt double knockout. The Deltauprt null mutant
      was prototrophic for pyrimidines but could not salvage uracil or any pyrimidine
      nucleoside. The capability of the Deltacps parasites to infect mice was somewhat
      diminished but still robust, indicating active pyrimidine salvage by the
      amastigote form of the parasite, but the Deltacps/Deltauprt mutant was completely
      attenuated with no persistent parasites detected after a 4-week infection.
      Complementation of the Deltacps/Deltauprt clone with either CPS or UPRT restored
      infectivity. These data establish that an intact pyrimidine biosynthesis pathway
      is essential for the growth of the promastigote form of L. donovani in culture,
      that all uracil and pyrimidine nucleoside salvage in the parasite is mediated by
      UPRT, and that both the biosynthetic and salvage pathways contribute to a robust
      infection of the mammalian host by the amastigote. These findings impact
      potential therapeutic design and vaccine strategies for visceral leishmaniasis.

PMID- 22367197
TI  - Structural characterization of Streptococcus pneumoniae serotype 9A capsule
      polysaccharide reveals role of glycosyl 6-O-acetyltransferase wcjE in serotype 9V
      capsule biosynthesis and immunogenicity.
AB  - The putative capsule O-acetyltransferase gene wcjE is highly conserved across
      various Streptococcus pneumoniae serotypes, but the role of the gene in capsule
      biosynthesis and bacterial fitness remains largely unclear. Isolates expressing
      pneumococcal serotype 9A arise from precursors expressing wcjE-associated
      serotype 9V through loss-of-function mutation to wcjE. To define the biosynthetic
      role of 9V wcjE, we characterized the structure and serological properties of
      serotype 9V and 9A capsule polysaccharide (PS). NMR data revealed that both 9V
      and 9A PS are composed of an identical pentasaccharide repeat unit, as reported
      previously. However, in sharp contrast to previous studies on 9A PS being devoid
      of any O-acetylation, we identified O-acetylation of alpha-glucuronic acid and
      alpha-glucose in 9A PS. In addition, 9V PS also contained -CH(2) O-acetylation of
      beta-N-acetylmannosamine, a modification that disappeared following in vitro
      recombinatorial deletion of wcjE. We also show that serotyping sera and
      monoclonal antibodies specific for 9V and 9A bound capsule PS in an O-acetate
      dependent manner. Furthermore, IgG and to a lesser extent IgM from human donors
      immunized with serotype 9V PS displayed stronger binding to 9V compared with 9A
      PS. We conclude that serotype 9V wcjE mediates 6-O-acetylation of beta-N
      acetylmannosamine. This PS modification can be selectively targeted by antibodies
      in immunized individuals, identifying a potential selective advantage for wcjE
      inactivation and serotype 9A emergence.

PMID- 22367198
TI  - Aminoglycoside 2''-phosphotransferase IIIa (APH(2'')-IIIa) prefers GTP over ATP:
      structural templates for nucleotide recognition in the bacterial aminoglycoside
      2'' kinases.
AB  - Contrary to the accepted dogma that ATP is the canonical phosphate donor in
      aminoglycoside kinases and protein kinases, it was recently demonstrated that all
      members of the bacterial aminoglycoside 2''-phosphotransferase IIIa (APH(2''))
      aminoglycoside kinase family are unique in their ability to utilize GTP as a
      cofactor for antibiotic modification. Here we describe the structural
      determinants for GTP recognition in these enzymes. The crystal structure of the
      GTP-dependent APH(2'')-IIIa shows that although this enzyme has templates for
      both ATP and GTP binding superimposed on a single nucleotide specificity motif,
      access to the ATP-binding template is blocked by a bulky tyrosine residue.
      Substitution of this tyrosine by a smaller amino acid opens access to the ATP
      template. Similar GTP binding templates are conserved in other bacterial
      aminoglycoside kinases, whereas in the structurally related eukaryotic protein
      kinases this template is less conserved. The aminoglycoside kinases are important
      antibiotic resistance enzymes in bacteria, whose wide dissemination severely
      limits available therapeutic options, and the GTP binding templates could be
      exploited as new, previously unexplored targets for inhibitors of these
      clinically important enzymes.

PMID- 22367200
TI  - Roles of telomerase reverse transcriptase N-terminal domain in assembly and
      activity of Tetrahymena telomerase holoenzyme.
AB  - Telomerase extends chromosome ends by the addition of single-stranded telomeric
      repeats. To support processive repeat synthesis, it has been proposed that
      coordination occurs between DNA interactions with the telomerase RNA template,
      the active site in the telomerase reverse transcriptase (TERT) core, a TERT N
      terminal (TEN) domain, and additional subunits of the telomerase holoenzyme
      required for telomere elongation in vivo. The roles of TEN domain surface
      residues in primer binding and product elongation have been studied largely using
      assays of minimal recombinant telomerase enzymes, which lack holoenzyme subunits
      that properly fold and conformationally stabilize the ribonucleoprotein and/or
      control its association with telomere substrates in vivo. Here, we use
      Tetrahymena telomerase holoenzyme reconstitution in vitro to assess TEN domain
      sequence requirements in the physiological enzyme context. We find that TEN
      domain sequence substitutions in the Tetrahymena telomerase holoenzyme influence
      synthesis initiation and elongation rate but not processivity. Functional and
      direct physical interaction assays pinpoint a conserved TEN domain surface
      required for holoenzyme subunit association and for high repeat addition
      processivity. Our results add to the understanding of telomerase holoenzyme
      architecture and TERT domain functions with direct implications for the unique
      mechanism of single-stranded repeat synthesis.

PMID- 22367199
TI  - Structure and mechanistic insights into novel iron-mediated moonlighting
      functions of human J-protein cochaperone, Dph4.
AB  - J-proteins are obligate cochaperones of Hsp70s and stimulate their ATPase
      activity via the J-domain. Although the functions of J-proteins have been well
      understood in the context of Hsp70s, their additional co-evolved "physiological
      functions" are still elusive. We report here the solution structure and mechanism
      of novel iron-mediated functional roles of human Dph4, a type III J-protein
      playing a vital role in diphthamide biosynthesis and normal development. The NMR
      structure of Dph4 reveals two domains: a conserved J-domain and a CSL-domain
      connected via a flexible linker-helix. The linker-helix modulates the
      conformational flexibility between the two domains, regulating thereby the
      protein function. Dph4 exhibits a unique ability to bind iron in tetrahedral
      coordination geometry through cysteines of its CSL-domain. The oxidized Fe-Dph4
      shows characteristic UV-visible and electron paramagnetic resonance spectral
      properties similar to rubredoxins. Iron-bound Dph4 (Fe-Dph4) also undergoes
      oligomerization, thus potentially functioning as a transient "iron storage
      protein," thereby regulating the intracellular iron homeostasis. Remarkably, Fe
      Dph4 exhibits vital redox and electron carrier activity, which is critical for
      important metabolic reactions, including diphthamide biosynthesis. Further, we
      observed that Fe-Dph4 is conformationally better poised to perform Hsp70
      dependent functions, thus underlining the significance of iron binding in Dph4.
      Yeast Jjj3, a functional ortholog of human Dph4 also shows a similar iron-binding
      property, indicating the conserved nature of iron sequestration across species.
      Taken together, our findings provide invaluable evidence in favor of additional
      co-evolved specialized functions of J-proteins, previously not well appreciated.

PMID- 22367201
TI  - Structural and biochemical characterization of glycoside hydrolase family 79 beta
      glucuronidase from Acidobacterium capsulatum.
AB  - We present the first structure of a glycoside hydrolase family 79 beta
      glucuronidase from Acidobacterium capsulatum, both as a product complex with beta
      D-glucuronic acid (GlcA) and as its trapped covalent 2-fluoroglucuronyl
      intermediate. This enzyme consists of a catalytic (beta/alpha)(8)-barrel domain
      and a beta-domain with irregular Greek key motifs that is of unknown function.
      The enzyme showed beta-glucuronidase activity and trace levels of beta
      glucosidase and beta-xylosidase activities. In conjunction with mutagenesis
      studies, these structures identify the catalytic residues as Glu(173) (acid base)
      and Glu(287) (nucleophile), consistent with the retaining mechanism demonstrated
      by (1)H NMR analysis. Glu(45), Tyr(243), Tyr(292)-Gly(294), and Tyr(334) form the
      catalytic pocket and provide substrate discrimination. Consistent with this, the
      Y292A mutation, which affects the interaction between the main chains of Gln(293)
      and Gly(294) and the GlcA carboxyl group, resulted in significant loss of beta
      glucuronidase activity while retaining the side activities at wild-type levels.
      Likewise, although the beta-glucuronidase activity of the Y334F mutant is ~200
      fold lower (k(cat)/K(m)) than that of the wild-type enzyme, the beta-glucosidase
      activity is actually 3 times higher and the beta-xylosidase activity is only 2.5
      fold lower than the equivalent parameters for wild type, consistent with a role
      for Tyr(334) in recognition of the C6 position of GlcA. The involvement of
      Glu(45) in discriminating against binding of the O-methyl group at the C4
      position of GlcA is revealed in the fact that the E45D mutant hydrolyzes PNP-beta
      GlcA approximately 300-fold slower (k(cat)/K(m)) than does the wild-type enzyme,
      whereas 4-O-methyl-GlcA-containing oligosaccharides are hydrolyzed only 7-fold
      slower.

PMID- 22367202
TI  - Cap snatching of yeast L-A double-stranded RNA virus can operate in trans and
      requires viral polymerase actively engaging in transcription.
AB  - Eukaryotic mRNA bears a cap structure (m(7)GpppX-) at the 5' terminus crucial for
      efficient translation and stability. The yeast L-A double-stranded RNA virus
      furnishes its mRNA with this structure by a novel cap-snatching mechanism in
      which the virus transfers an m(7)Gp moiety from host mRNA to the diphosphorylated
      5' terminus of the viral transcript, thus forming on it an authentic cap
      structure (referred to as cap0) in the budding yeast. This capping reaction is
      essential for efficient viral expression. His-154 of the capsid protein Gag is
      involved in the cap transfer. Here we show that the virus can utilize an
      externally added viral transcript as acceptor in the capping reaction. The
      acceptor needs to be 5' diphosphorylated, consistent with the fact that the viral
      transcript bears diphosphate at the 5' terminus. A 5' triphosphorylated or
      monophosphorylated transcript does not function as acceptor. N7 methylation at
      the 5' cap guanine of mRNA is essential for cap donor activity. We also
      demonstrate that the capping reaction requires the viral polymerase actively
      engaging in transcription. Because the cap-snatching site of Gag is located at
      the cytoplasmic surface of the virion, whereas Pol is confined inside the virion,
      the result indicates coordination between the cap-snatching and polymerization
      sites. This will allow L-A virus to efficiently produce capsid proteins to form
      new virions when Pol is actively engaging in transcription. The coordination may
      also minimize the risk of accidental capping of nonviral RNA when Pol is dormant.

PMID- 22367203
TI  - Subunit interactions at the V1-Vo interface in yeast vacuolar ATPase.
AB  - Eukaryotic vacuolar ATPase (V-ATPase) is regulated by a reversible dissociation
      mechanism that involves breaking and reforming of protein-protein interactions at
      the interface of the V(1)-ATPase and V(o)-proton channel domains. We found
      previously that the head domain of the single copy C subunit (C(head)) binds one
      subunit EG heterodimer with high affinity (Oot, R.A. and Wilkens, S. (2010) J.
      Biol. Chem. 285, 24654-24664). Here we generated a water-soluble construct of the
      N-terminal domain of the V(o) "a" subunit composed of amino acid residues 104-372
      (a(NT(104-372))). Analytical gel filtration chromatography and sedimentation
      velocity analysis revealed that a(NT(104-372)) undergoes reversible dimerization
      in a concentration-dependent manner. A low-resolution molecular envelope was
      calculated for the a(NT(104-372)) dimer using small angle x-ray scattering data.
      Isothermal titration calorimetry experiments revealed that a(NT(104-372)) binds
      the C(foot) and EG heterodimer with dissociation constants of 22 and 33 MUM,
      respectively. We speculate that the spatial closeness of the a(NT), C(foot), and
      EG binding sites in the intact V-ATPase results in a high-avidity interaction
      that is able to resist the torque of rotational catalysis, and that reversible
      enzyme dissociation is initiated by breaking either the a(NT(104-372))-C(foot) or
      a(NT(104-372))-EG interaction by an as-yet unknown signaling mechanism.

PMID- 22367204
TI  - Position-dependent effects of polylysine on Sec protein transport.
AB  - The bacterial Sec protein translocation system catalyzes the transport of
      unfolded precursor proteins across the cytoplasmic membrane. Using a recently
      developed real time fluorescence-based transport assay, the effects of the number
      and distribution of positive charges on the transport time and transport
      efficiency of proOmpA were examined. As expected, an increase in the number of
      lysine residues generally increased transport time and decreased transport
      efficiency. However, the observed effects were highly dependent on the polylysine
      position in the mature domain. In addition, a string of consecutive positive
      charges generally had a more significant effect on transport time and efficiency
      than separating the charges into two or more charged segments. Thirty positive
      charges distributed throughout the mature domain resulted in effects similar to
      10 consecutive charges near the N terminus of the mature domain. These data
      support a model in which the local effects of positive charge on the
      translocation kinetics dominate over total thermodynamic constraints. The rapid
      translocation kinetics of some highly charged proOmpA mutants suggest that the
      charge is partially shielded from the electric field gradient during transport,
      possibly by the co-migration of counter ions. The transport times of precursors
      with multiple positively charged sequences, or "pause sites," were fairly well
      predicted by a local effect model. However, the kinetic profile predicted by this
      local effect model was not observed. Instead, the transport kinetics observed for
      precursors with multiple polylysine segments support a model in which
      translocation through the SecYEG pore is not the rate-limiting step of transport.

PMID- 22367205
TI  - Characterization of DeltaN-Zfp36l2 mutant associated with arrest of early
      embryonic development and female infertility.
AB  - The zinc finger protein 36-like 2, Zfp36l2, has been implicated in female mouse
      infertility, because an amino-terminal truncation mutation (DeltaN-Zfp36l2) leads
      to two-cell stage arrest of embryos derived from the homozygous mutant female
      gamete. Zfp36l2 is a member of the tristetraprolin (TTP) family of CCCH tandem
      zinc finger proteins that can bind to transcripts containing AU-rich elements
      (ARE), resulting in deadenylation and destabilization of these transcripts. I
      show here that the mouse Zfp36l2 is composed of two exons and a single intron,
      encoding a polypeptide of 484 amino acids. I observed that DeltaN-Zfp36l2 protein
      is similar to both wild-type Zfp36l2 and TTP (Zfp36) in that it shuttles between
      the cytoplasm and nucleus, binds to RNAs containing AREs, and promotes
      deadenylation of a model ARE transcript in a cell-based co-transfection assay.
      Surprisingly, in contrast to TTP, Zfp36l2 mRNA and protein were rapidly down
      regulated upon LPS exposure in bone marrow-derived macrophages. The DeltaN
      Zfp36l2 protein was substantially more resistant to stimulus-induced down
      regulation than the WT. I postulate that the embryonic arrest linked to the
      DeltaN-Zfp36l2 truncation might be related to its resistance to stimulus-induced
      down-regulation.

PMID- 22367206
TI  - Myosin-1A targets to microvilli using multiple membrane binding motifs in the
      tail homology 1 (TH1) domain.
AB  - One of the most abundant components of the enterocyte brush border is the actin
      based monomeric motor, myosin-1a (Myo1a). Within brush border microvilli, Myo1a
      carries out a number of critical functions at the interface between membrane and
      actin cytoskeleton. Proper physiological function of Myo1a depends on its ability
      to bind to microvillar membrane, an interaction mediated by a C-terminal tail
      homology 1 (TH1) domain. However, little is known about the mechanistic details
      of the Myo1a-TH1/membrane interaction. Structure-function analysis of Myo1a-TH1
      targeting in epithelial cells revealed that an N-terminal motif conserved among
      class I myosins and a C-terminal motif unique to Myo1a-TH1 are both required for
      steady state microvillar enrichment. Purified Myo1a bound to liposomes composed
      of phosphatidylserine and phosphoinositol 4,5-bisphosphate, with moderate
      affinity in a charge-dependent manner. Additionally, peptides of the N- and C
      terminal regions required for targeting were able to compete with Myo1a for
      binding to highly charged liposomes in vitro. Single molecule total internal
      reflection fluorescence microscopy showed that these motifs are also necessary
      for slowing the membrane detachment rate in cells. Finally, Myo1a-TH1 co
      localized with both lactadherin-C2 (a phosphatidylserine-binding protein) and
      PLCdelta1-PH (a phosphoinositol 4,5-bisphosphate-binding protein) in microvilli,
      but only lactaderin-C2 expression reduced brush border targeting of Myo1a-TH1.
      Together, our results suggest that Myo1a targeting to microvilli is driven by
      membrane binding potential that is distributed throughout TH1 rather than
      localized to a single motif. These data highlight the diversity of mechanisms
      that enable different class I myosins to target membranes in distinct biological
      contexts.

PMID- 22367207
TI  - A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth
      factor 1 receptor: implications in postnatal cardiac remodeling and cell
      survival.
AB  - Postnatal cardiac remodeling is characterized by a marked decrease in the insulin
      like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) expression. The underlying
      mechanism remains unexplored. This study examined the role of microRNAs in
      postnatal cardiac remodeling. By expression profiling, we observed a 10-fold
      increase in miR-378 expression in 1-week-old neonatal mouse hearts compared with
      16-day-old fetal hearts. There was also a 4-6-fold induction in expression of miR
      378 in older (10 months) compared with younger (1 month) hearts. Interestingly,
      tissue distribution analysis identified miR-378 to be highly abundant in heart
      and skeletal muscles. In the heart, specific expression was observed in cardiac
      myocytes, which was inducible by a variety of stressors. Overexpression of miR
      378 enhanced apoptosis of cardiomyocytes by direct targeting of IGF1R and reduced
      signaling in Akt cascade. The inhibition of miR-378 by its anti-miR protected
      cardiomyocytes against H(2)O(2) and hypoxia reoxygenation-induced cell death by
      promoting IGF1R expression and downstream Akt signaling cascade. Additionally,
      our data show that miR-378 expression is inhibited by IGF1 in cardiomyocytes. In
      tissues such as fibroblasts and fetal hearts, where IGF1 levels are high, we
      found either absent or significantly low miR-378 levels, suggesting an inverse
      relationship between these two factors. Our study identifies miR-378 as a new
      cardioabundant microRNA that targets IGF1R. We also demonstrate the existence of
      a negative feedback loop between miR-378, IGF1R, and IGF1 that is associated with
      postnatal cardiac remodeling and with the regulation of cardiomyocyte survival
      during stress.

PMID- 22367208
TI  - Targeted gene inactivation of calpain-1 suppresses cortical degeneration due to
      traumatic brain injury and neuronal apoptosis induced by oxidative stress.
AB  - Calpains are calcium-regulated cysteine proteases that have been implicated in
      the regulation of cell death pathways. Here, we used our calpain-1 null mouse
      model to evaluate the function of calpain-1 in neural degeneration following a
      rodent model of traumatic brain injury. In vivo, calpain-1 null mice show
      significantly less neural degeneration and apoptosis and a smaller contusion 3
      days post-injury than wild type littermates. Protection from traumatic brain
      injury corroborated with the resistance of calpain-1 neurons to apoptosis induced
      by oxidative stress. Biochemical analysis revealed that caspase-3 activation,
      extracellular calcium entry, mitochondrial membrane permeability, and release of
      apoptosis-inducing factor from mitochondria are partially blocked in the calpain
      1 null neurons. These findings suggest that the calpain-1 knock-out mice may
      serve as a useful model system for neuronal protection and apoptosis in traumatic
      brain injury and other neurodegenerative disorders in which oxidative stress
      plays a role.

PMID- 22367209
TI  - Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and
      actin dynamics to promote neuronal progenitor cell migration.
AB  - Doublecortin (DCX) is a microtubule-associated protein that is specifically
      expressed in neuronal cells. Genetic mutation of DCX causes lissencephaly
      disease. Although the abnormal cortical lamination in lissencephaly is thought to
      be attributable to neuronal cell migration defects, the regulatory mechanisms
      governing interactions between DCX and cytoskeleton in the migration of neuronal
      progenitor cells remain obscure. In this study we found that the G(s) and protein
      kinase A (PKA) signal elicited by pituitary adenylate cyclase-activating
      polypeptide promotes neuronal progenitor cells migration. Stimulation of G(s)-PKA
      signaling prevented microtubule bundling and induced the dissociation of DCX from
      microtubules in cells. PKA phosphorylated DCX at Ser-47, and the phospho
      mimicking mutant DCX-S47E promoted cell migration. Activation of PKA and DCX-S47E
      induced lamellipodium formation. Pituitary adenylate cyclase-activating
      polypeptide and DCX-S47E stimulated the activation of Rac1, and DCX-S47E
      interacted with Asef2, a guanine nucleotide exchange factor for Rac1. Our data
      reveal a dual reciprocal role for DCX phosphorylation in the regulation of
      microtubule and actin dynamics that is indispensable for proper brain lamination.

PMID- 22367210
TI  - Microtubules regulate hypoxia-inducible factor-1alpha protein trafficking and
      activity: implications for taxane therapy.
AB  - Disruption of the microtubule cytoskeleton impairs tumor angiogenesis by
      inhibiting the hypoxia-inducible factor (HIF-1alpha) pathway. However, the
      signaling cascade linking microtubule disruption to HIF-1alpha inactivation has
      not been elucidated. Here, we show that microtubule-targeting drug (MTD)
      treatment impaired HIF-1alpha protein nuclear translocation, which significantly
      down-regulated HIF transcriptional activity. We provide strong evidence that HIF
      1alpha protein associates with polymerized microtubules and traffics to the
      nucleus, with the aid of the dynein motor protein. Together, these data suggest
      that microtubules are critically involved in the nuclear trafficking and
      transcriptional activity of HIF-1alpha. We also show that the connection between
      the microtubule cytoskeleton and HIF-1alpha regulation is lost in renal cell
      carcinoma (RCC), where HIF-1alpha is overexpressed because of mutations in the
      von Hippel Lindau (VHL) tumor suppressor protein. Specifically, we show that MTD
      treatment of RCC cells did not impair HIF-1alpha nuclear accumulation or
      transcriptional activity, and had no effect on the polysome association profile
      of HIF-1alpha. Interestingly, we found that HIF-1alpha protein did not bind
      microtubules in RCC. Moreover, restoration of VHL function failed to restore the
      ability of MTDs to inhibit HIF-1alpha, suggesting that VHL does not contribute to
      this phenotype. Together, these results suggest that HIF-1alpha regulation is
      microtubule-independent, and likely contributes to the chemoresistant nature of
      RCCs. Further understanding of the microtubule-dependent HIF-1alpha regulation,
      and lack thereof in RCC, is essential given the importance of HIF-1alpha in tumor
      biology, and the widespread use of MTDs in clinical oncology.

PMID- 22367211
TI  - Molecular basis of dynamic relocalization of Dictyostelium myosin IB.
AB  - Class I myosins have a single heavy chain comprising an N-terminal motor domain
      with actin-activated ATPase activity and a C-terminal globular tail with a basic
      region that binds to acidic phospholipids. These myosins contribute to the
      formation of actin-rich protrusions such as pseudopodia, but regulation of the
      dynamic localization to these structures is not understood. Previously, we found
      that Acanthamoeba myosin IC binds to acidic phospholipids in vitro through a
      short sequence of basic and hydrophobic amino acids, BH site, based on the charge
      density of the phospholipids. The tail of Dictyostelium myosin IB (DMIB) also
      contains a BH site. We now report that the BH site is essential for DMIB binding
      to the plasma membrane and describe the molecular basis of the dynamic
      relocalization of DMIB in live cells. Endogenous DMIB is localized uniformly on
      the plasma membrane of resting cells, at active protrusions and cell-cell
      contacts of randomly moving cells, and at the front of motile polarized cells.
      The BH site is required for association of DMIB with the plasma membrane at all
      stages where it colocalizes with phosphoinositide bisphosphate/phosphoinositide
      trisphosphate (PIP(2)/PIP(3)). The charge-based specificity of the BH site allows
      for in vivo specificity of DMIB for PIP(2)/PIP(3) similar to the PH domain-based
      specificity of other class I myosins. However, DMIB-head is required for
      relocalization of DMIB to the front of migrating cells. Motor activity is not
      essential, but the actin binding site in the head is important. Thus, dynamic
      relocalization of DMIB is determined principally by the local PIP(2)/PIP(3)
      concentration in the plasma membrane and cytoplasmic F-actin.

PMID- 22367212
TI  - Clinicopathological and biological significance of human voltage-gated proton
      channel Hv1 protein overexpression in breast cancer.
AB  - In our previous work, we showed for the first time that the voltage-gated proton
      channel Hv1 is specifically expressed in highly metastatic human breast tumor
      tissues and cell lines. However, the contribution of Hv1 to breast carcinogenesis
      is not well known. In this study, we showed that Hv1 expression was significantly
      correlated with the tumor size (p = 0.001), tumor classification (p = 0.000),
      lymph node status (p = 0.000), clinical stage (p = 0.000), and Her-2 status (p =
      0.045). High Hv1 expression was associated significantly with shorter overall (p
      = 0.000) and recurrence-free survival (p = 0.000). In vitro, knockdown of Hv1
      expression in the highly metastatic MDA-MB-231 cells decreased the cell
      proliferation and invasiveness, inhibited the cell proton secretion and
      intracellular pH recovery, and blocked the cell capacity of acidifying
      extracellular milieu. Furthermore, the gelatinase activity in MDA-MB-231 cells
      that suppressed Hv1 was reduced. In vivo, the breast tumor size of the
      implantation of the MDA-MB-231 xenografts in nude mice that were knocked down by
      Hv1 was dramatically smaller than that in the control groups. The results
      demonstrated that the inhibition of Hv1 function via knockdown of Hv1 expression
      can effectively retard the cancer growth and suppress the cancer metastasis by
      the decrease of proton extrusion and the down-regulation of gelatinase activity.
      Based on these results, we came to the conclusion that Hv1 is a potential
      biomarker for prognosis of breast cancer and a potential target for anticancer
      drugs in breast cancer therapy.

PMID- 22367213
TI  - A potent vaccination strategy that circumvents lymphodepletion for effective
      antitumor adoptive T-cell therapy.
AB  - Adoptive cell therapy using tumor-reactive T lymphocytes is a promising approach
      for treating advanced cancer. Successful tumor eradication depends primarily on
      the expansion and survival of the adoptively transferred T cells. Lymphodepletion
      using total body irradiation (TBI) and administering high-dose interleukin (IL)-2
      have been used with adoptive cell therapy to promote T-cell expansion and
      survival to achieve maximal therapeutic effects. However, TBI and high-dose IL-2
      increase the risk for major complications that impact overall survival. Here we
      describe an alternative approach to TBI and high-dose IL-2 for optimizing
      adoptive cell therapy, resulting in dramatic therapeutic effects against
      established melanomas in mice. Administration of a potent, noninfectious peptide
      vaccine after adoptive cell therapy dramatically increased antigen-specific T
      cell numbers leading to enhancement in the survival of melanoma-bearing mice.
      Furthermore, combinations of peptide vaccination with PD1 blockade or IL-2/anti
      IL-2 antibody complexes led to complete disease eradication and long-term
      survival in mice with large tumors receiving adoptive cell therapy. Our results
      indicate that PD1 blockade and IL-2/anti-IL-2 complexes enhance both the
      quantitative and qualitative aspects of the T-cell responses induced by peptide
      vaccination after adoptive cell therapy. These findings could be useful for the
      optimization of adoptive cell therapy in cancer patients without the need of
      toxic adjunct procedures.

PMID- 22367214
TI  - Characterization of gene-environment interactions for colorectal cancer
      susceptibility loci.
AB  - Genome-wide association studies (GWAS) have identified more than a dozen loci
      associated with colorectal cancer (CRC) risk. Here, we examined potential effect
      modification between single-nucleotide polymorphisms (SNP) at 10 of these loci
      and probable or established environmental risk factors for CRC in 7,016 CRC cases
      and 9,723 controls from nine cohort and case-control studies. We used meta
      analysis of an efficient empirical-Bayes estimator to detect potential
      multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3
      (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842),
      rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13
      (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at
      19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk
      factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti
      inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red
      meat, processed meat, vegetables, fruit, and fiber). The strongest statistical
      evidence for a gene-environment interaction across studies was for vegetable
      consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and
      UTP23 genes (nominal P(interaction) = 1.3 * 10(-4); adjusted P = 0.02). The
      magnitude of the main effect of the SNP increased with increasing levels of
      vegetable consumption. No other interactions were statistically significant after
      adjusting for multiple comparisons. Overall, the association of most CRC
      susceptibility loci identified in initial GWAS seems to be invariant to the other
      risk factors considered; however, our results suggest potential modification of
      the rs16892766 effect by vegetable consumption.

PMID- 22367215
TI  - Concordant release of glycolysis proteins into the plasma preceding a diagnosis
      of ER+ breast cancer.
AB  - Although the identification of peripheral blood biomarkers would enhance early
      detection strategies for breast cancer, the discovery of protein markers has been
      challenging. In this study, we sought to identify coordinated changes in plasma
      proteins associated with breast cancer based on large-scale quantitative mass
      spectrometry. We analyzed plasma samples collected up to 74 weeks before
      diagnosis from 420 estrogen receptor (ER)(+) cases and matched controls enrolled
      in the Women's Health Initiative cohort. A gene set enrichment analysis was
      applied to 467 quantified proteins, linking their corresponding genes to
      particular biologic pathways. On the basis of differences in the concentration of
      individual proteins, glycolysis pathway proteins exhibited a statistically
      significant difference between cases and controls. In particular, the enrichment
      was observed among cases in which blood was drawn closer to diagnosis (effect
      size for the 0-38 weeks prediagnostic group, 1.91; P, 8.3E-05). Analysis of
      plasmas collected at the time of diagnosis from an independent set of cases and
      controls confirmed upregulated levels of glycolysis proteins among cases relative
      to controls. Together, our findings indicate that the concomitant release of
      glycolysis proteins into the plasma is a pathophysiologic event that precedes a
      diagnosis of ER(+) breast cancer.

PMID- 22367216
TI  - Dermoscopic changes in melanocytic naevi in children during digital follow-up.
AB  - The aim of this study was to investigate the dermoscopic changes in acquired
      melanocytic naevi in a large paediatric population over an interval of several
      years. Images of 717 melanocytic naevi were obtained from 160 consecutive
      patients. Dermoscopic pigment pattern changes were observed in one of two lesions
      after a follow-up of one year, in 34 of 295 lesions (11.5%) after 2 years, in 40
      of 190 lesions (21.1%) after 3 years, in 40 of 141 lesions (28.4%) after 4 years,
      in 5 of 37 lesions (13.5%) after 5 years, in 12 of 31 lesions (38.8%) after 6
      years, and in 7 of 21 lesions (33.3%) after 7 years. Dermoscopic changes were
      detected in 25.3% of the lesions in patients aged 3-6 years, in 21% of the
      lesions in patients aged 7-12 years, and in 15.5% of the lesions in patients over
      13 years. Main pattern changes consisted of transition from globular to globular
      reticular (35 naevi), from globular to reticular (14 naevi) and from globular
      reticular to reticular (24 naevi). These results are consistent with the view
      that melanocytic naevi generally undergo a characteristic transition from a
      globular pattern to a reticular pattern. Most of the changes are observed in the
      3-6 years age group when hormonal and/or environmental factors are not thought to
      play a role in pattern alterations.

PMID- 22367217
TI  - "Vacuum-assisted staining": a simple and efficient method for screening in
      Drosophila.
AB  - The constantly growing number of genetic tools rapidly increases possibilities
      for various screens in different model organisms and calls for new methods
      facilitating screen performance. In particular, screening procedures involving
      fixation and staining of samples are difficult to perform at a genome-wide scale.
      The time-consuming task to generate these samples makes such screens less
      attractive. Here, we describe the use of multi-well filter plates for high
      throughput labellings of different Drosophila organs and zebrafish embryos. Our
      inexpensive vacuum-assisted staining protocol minimises the risk of sample loss,
      reduces the amount of staining reagents and drastically decreases labour and
      repetitive work. The simple handling of the system and the commercial
      availability of its components makes this method easily applicable to every
      laboratory.

PMID- 22367218
TI  - Ocular dermoids:  116 consecutive cases.
AB  - PURPOSE: The aim was to describe the demographic and clinical data of 116
      consecutive cases of ocular dermoids. METHODS: This was a retrospective case
      series and a review of clinical records of all the patients diagnosed with ocular
      dermoids. Both demographic and clinical data were recorded. Statistical analysis
      was performed with SPSS v. 18. Descriptive statistics are reported. RESULTS: The
      study included 116 consecutive patients with diagnosis consistent with ocular
      dermoids: corneal 18% (21), dermolipomas 38% (44), and orbital 44% (51). Sixty
      five percent (71) were female, and 46% (54) were detected at birth. Secondary
      manifestations: amblyopia was present in 14% (3), and strabismus was detected in
      6.8% (8). The Goldenhar syndrome was the most frequent syndromic entity in 7.5%
      (12) of the patients. Surgical resection was required on 49% (25) of orbital
      dermoids, 24% (5) of corneal dermoids, and 13% (6) of dermolipomas. CONCLUSIONS:
      Orbital dermoids were the most frequent variety, followed by conjunctival and
      corneal. In contrast to other reports, corneal dermoids were significantly more
      prevalent in women. Goldenhar syndrome was the most frequent syndromatic entity.

PMID- 22367219
TI  - Hypoxia-induced downregulation of DeltaNp63alpha in the corneal epithelium.
AB  - PURPOSE: The aim of this study was to establish a relationship between hypoxic
      stress and the expression of DeltaNp63alpha in an established rabbit contact lens
      model and in cultured corneal epithelial cells. METHODS: New Zealand white
      rabbits were fit in one eye with either a non-oxygen transmissible or hyper
      oxygen-permeable rigid contact lens for 24 hrs of wear; the contralateral eye was
      used as a control. All the rabbits underwent a bilateral nictitating
      membranectomy to facilitate lens retention. DeltaNp63alpha expression was
      analyzed by immunofluorescence and western blot. Telomerase-immortalized human
      corneal epithelial cells (hTCEpi) were grown in serum-free media and treated with
      the hypoxia-mimetic cobalt chloride to simulate hypoxia for 6 hrs (short term) or
      24 hrs (prolonged). Transcriptional activity and protein levels were assessed
      using luciferase reporter assays, reverse transcription polymerase chain
      reaction, and western blot. Cell viability was assessed by live/dead assay.
      RESULTS: Compared with the non-lens wearing eye, 24 hrs of non-oxygen
      transmissible lens wear in vivo decreased DeltaNp63alpha protein levels in both
      the limbal and central corneal epithelium; this decrease was not found in the
      hyper-oxygen transmissible lens group. In hTCEpi cells in vitro, hypoxia
      increased the activity of the DeltaN promoter but reduced the levels of
      DeltaNp63alpha mRNA after 24 hrs of prolonged culture. Similarly, DeltaNp63alpha
      expression levels were unaffected from short-term exposure but decreased after 24
      hrs. Live/dead assay confirmed the presence of viable cells after CoCl2 treatment
      at 6- and 24-hr time points. Cells treated for 24 hrs were viable but were
      smaller and rounded with signs of membrane blebbing, consistent with early stages
      of apoptosis. CONCLUSIONS: Hypoxic stress induced by either prolonged wear of a
      nonoxygen transmissible lens in vivo or hypoxic-mimic conditions by cobalt
      chloride in vitro downregulates DeltaNp63alpha in the corneal epithelium. The
      loss of DeltaNp63alpha in response to hypoxic stress may contribute to the
      disruption of normal renewal mechanisms reported with low oxygen transmissible
      contact lens wear and prolonged eyelid closure.

PMID- 22367220
TI  - Fluid-filled scleral contact lenses in vernal keratoconjunctivitis.
AB  - OBJECTIVES: The purpose of this study is to report on the use of fluid-filled
      scleral contact lenses (F-ScCL) in patients with vernal keratoconjunctivitis
      (VKC). METHODS: We retrospectively reviewed charts of four patients who had worn
      F-ScCL (PROSE, Boston Foundation for Sight, Needham Heights, MA) from July 2006
      for VKC with two associated conditions; keratoconus and limbal stem-cell
      deficiency (LSCD). Any previous refractive correction or complications were
      noted. The main goal of fitting F-ScCL was to improve visual acuity in
      keratoconus and to improve the ocular microenvironment in LSCD. Visual acuity
      before and during lens wear and the average wearing time in hours per day was
      noted. RESULTS: Four patients (7 eyes) with VKC wore F-ScCL for associated
      keratoconus (n=5 eyes), LSCD (n=2 eyes). The mean age of the patients was 17. 5
      years. The LogMAR visual acuity was 0.4 and 0.18 before and during lens wear,
      respectively, at a mean follow-up of 14.8 months. The average lens wear was 8.30
      hrs per day. Two patients developed acute hydrops at 2 and 12 months of lens wear
      and underwent descematopexy. Visual acuity with F-ScCL reduced by more than two
      lines because of the scar of healed hydrops. Of the 3 patients with keratoconus,
      1 patient had used a piggy back lens system for 2.5 years before F-ScCL wear, and
      2 patients had failed with rigid gas-permeable lens trial lenses. CONCLUSIONS:
      With coexisting keratoconus and VKC, F-ScCL improves vision and helps to maintain
      the health of the ocular surface.

PMID- 22367221
TI  - Propofol exerts hippocampal neuron protective effects via up-regulation of
      metallothionein-3.
AB  - Propofol is an intravenous anesthetic with neuroprotective effects against
      cerebral ischemia or hypoxia injury. However, the underlying mechanisms remain
      obscure. Recent years emerging evidence has demonstrated that metallothionein-3
      (MT-3), a growth inhibitory factor that exists mainly in the central nervous
      system, exhibited neuroprotective effect in vivo. Here, we used a model of
      hypoxia/re-oxygenation (H/R) injury to examine the hippocampal neuroprotective
      effect of propofol, and explored the role of MT-3 in this action. H/R resulted in
      reduced cell viability and increased cell death in hippocampal neuron culture, as
      indicated by MTT assay and lactate dehydrogenase (LDH) release assay,
      respectively. Pretreatment of propofol at different concentrations (50, 150, and
      250 MUmol/L) reversed H/R-induced neurotoxicity and increased MT-3 mRNA and
      protein expressions. Moreover, propofol failed to exert neuroprotective effect
      when MT-3 was silenced by the transfection with the specific siRNA, suggesting
      that MT-3 was the crucial mediator for propofol's neuroprotective effect against
      H/R. In conclusion, our findings showed that propofol is neuroprotective in H/R
      model on hippocampal neuron cells and that it may act by up-regulation of MT-3.

PMID- 22367222
TI  - Health-related quality of life outcomes at 1 and 5 years after a residential
      retreat promoting lifestyle modification for people with multiple sclerosis.
AB  - There is a strong body of evidence that supports the use of non-drug therapies in
      the management of people with multiple sclerosis (MS). A 5-day residential
      retreat for people with MS in Victoria, Australia, promotes lifestyle
      modification within a patient-centred model of care. Analysis of the health
      related quality of life (HRQOL) of the retreat participants was undertaken using
      the MSQOL-54, prior to attendance, 1 and 5 years after the retreat. 274 retreat
      participants (71%) completed baseline questionnaires. Despite the usually
      progressive nature of MS, the cohort demonstrated clinically and statistically
      significant improvements in HRQOL. One year after attending the retreat, median
      improvements of 11.3% were observed in the overall quality of life domain (p <
      0.001); 18.6% in the physical health composite (p < 0.001); and 11.8% in the
      mental health composite (p < 0.001). In the subset of 165 who had reached the 5
      year time-point, there was a 19.5% median improvement in overall quality of life
      (p < 0.001); 17.8% in the physical health composite (p < 0.001) and 22.8% in the
      mental health composite (p < 0.001), compared to baseline. Attendance at a
      retreat promoting lifestyle modification for the integrated management of MS
      appears to have positive effects on short and medium-term HRQOL. Non-drug
      therapies should be considered as part of any comprehensive treatment plan for
      people with MS.

PMID- 22367223
TI  - Prevalence of cardiac right left shunts in migraine: a population-based case
      control study.
AB  - We aimed to investigate the prevalence of cardiac right left shunts (RLS) in
      population-based samples of subjects with migraine with aura (n = 42), migraine
      without aura (n = 44) and controls without headache (n = 41). Cardiac RLS was
      assessed with transcranial Doppler sonography with intravenous injection of
      saline. Prevalence of RLS was highest in migraineurs with aura (45.2%) compared
      to migraineurs without aura (34.1%) and controls (41.5%). Permanent as opposed to
      latent RLS was more common among patients with migraine with aura (40.5%) than in
      patients with migraine without aura (23.3%) or controls (24.4%). Differences did
      not reach statistical significance between the three groups (p = 0.564 for RLS
      prevalence, p = 0.349 for prevalence of permanent shunts). Our data implicate a
      trend towards higher prevalence of RLS with larger shunts in subjects with
      migraine with aura.

PMID- 22367224
TI  - Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial
      spasm: a nerve conduction study.
AB  - Botulinum toxin type-A is currently thought to be effective and safe for
      hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the
      neuromuscular junction induces depression of orbicularis oculi muscle compound
      motor action potential (CMAP). The aim of our study was to evaluate at what
      extent end-plate functional recovery is possible even in botulinum toxin
      treatments lasting up to 15 years. We examined 81 outpatients with primary HFS
      (mean treatment duration = 7.2 +/- 4.2 years) who underwent neurophysiologic
      study, once clinical effect of the previous treatment had vanished. The mean CMAP
      amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and
      area of response 2 (R2) of treated orbicularis oculi muscle were measured in
      comparison to the controlateral side. Mean amplitude of the above mentioned
      parameters was slightly lower (about 20%; p < 0.001) in the treated side at the
      end of the follow-up period (4.7 +/- 1.7 months). The CMAP amplitude reduction
      weakly correlated with the interval from last treatment, while other
      neurophysiologic parameters did not change due to treatment duration or total
      toxin amount. Our study demonstrates that botulinum toxin affects compound motor
      action potential and blink-reflex responses for at least 4-5 months in HFS
      patients. The residual block is slight and does not increase with repeated
      injections after several years of treatment. Our study, beside confirming the
      long-term efficacy of botulinum toxin treatment for HFS, provides
      neurophysiologic evidence that therapeutic effect may be obtained without
      hindering the regenerative potential of the nerve-muscle complex.

PMID- 22367225
TI  - Thumb, forefinger, and lip numbness: a distinctive thalamic lacunar syndrome.

PMID- 22367226
TI  - Testing the relation between dispositional optimism and conditioned pain
      modulation: does ethnicity matter?
AB  - Greater dispositional optimism has been related to less severe pain; however,
      whether optimism is associated with endogenous pain modulation has not yet been
      examined. The beneficial effects of dispositional optimism often vary according
      to cultural dynamics. Thus, assessing optimism-pain relationships across
      different ethnic groups is warranted. This study sought to examine the
      association between optimism and conditioned pain modulation (CPM), and test
      whether this association differs according to ethnicity. Optimism and CPM were
      assessed in a sample of healthy, ethnically diverse young adults. CPM was
      determined by comparing pressure pain thresholds obtained before and during
      exposure to a cold pressor task. All participants completed a validated measure
      of dispositional optimism. Greater reported optimism was significantly associated
      with enhanced CPM, and the strength of this association did not vary according to
      individuals' ethnic background. These findings suggest that an optimistic
      disposition may potentiate endogenous pain inhibition.

PMID- 22367227
TI  - A study of the potential application of nano-Mg(OH)2 in adsorbing low
      concentrations of uranyl tricarbonate from water.
AB  - This work aims at the investigation of nano-Mg(OH)(2) as a promising adsorbent
      for uranium recovery from water. Systematic analysis including the uranium
      adsorption isotherm, the kinetics and the thermodynamics of adsorption of low
      concentrations of uranyl tricarbonate (0.1-20 mg L(-1)) by nano-Mg(OH)(2) was
      carried out. The results showed a spontaneous and exothermic uranium adsorption
      process by Mg(OH)(2), which could be well described with pseudo second order
      kinetics. Surface site calculation and zeta potential measurement further
      demonstrated that UO(2)(CO(3))(3)(4-) was a monolayer adsorbed onto nano
      Mg(OH)(2) by electrostatic forces. Accordingly, the adsorption behavior met the
      conditions of the Langmuir isotherm. Moreover, in most of the reported
      literature, nano-Mg(OH)(2) had a higher UO(2)(CO(3))(3)(4-) adsorption affinity
      b, which implied a higher adsorption amount at equilibrium in a dilute adsorbate
      system. The significance of the adsorption affinity b for choosing and designing
      adsorbents with respect to low concentration of resources/pollutants treatment
      has also been assessed.

PMID- 22367228
TI  - Downregulation of LH receptor mRNA in the rat uterus.
AB  - We detected luteinizing hormone receptor (LHR) mRNA in the immature rat uterus by
      northern blotting and downregulation of this receptor mRNA after pregnant mare
      serum gonadotropin (PMSG)-human chorionic gonadotropin (hCG) treatment. After
      administration of hCG, the mRNA levels in the rat uterus declined to an extremely
      low level from Days 1 to 3 and then rebounded and reached higher than
      pretreatment values at Day 4. At Day 5 the levels were 3-fold higher than the
      control levels. The cultured uterus displayed an hCG concentration-dependent
      increase in cAMP production in the medium. Immunohistochemical experiments showed
      that these receptor proteins were expressed in the epithelial cells of the
      endometrium. These results suggest that functional LHRs are present in the
      immature rat uterus and are downregulated by signals resulting from hCG
      treatment. These data may support the idea that LH acts on the uterus to inhibit
      contraction at ovulation. Although the precise role of the LHR in the uterus
      remains unknown, this study may provide a model with which to investigate the
      regulation of LHR.

PMID- 22367229
TI  - A heat shock protein gene, CsHsp45.9, involved in the response to diverse
      stresses in cucumber.
AB  - Heat shock proteins (Hsps) are a family of highly conserved proteins present in
      all organisms. They mediate a range of cytoprotective functions as molecular
      chaperones and are recently reported to regulate the immune response. Using
      suppression subtractive hybridization, we isolated and characterized a cucumber
      cDNA, designated CsHsp45.9, which encodes a putative heat shock protein of 45.9
      kDa protein, containing three conserved DnaJ domains belonging to the Type I
      Hsp40 family. Real-time quantitative RT-PCR analysis revealed that CsHsp45.9 was
      significantly induced in cucumber leaves inoculated with downy mildew
      (Pseudoperonospora cubensis) in this incompatible interaction. Gene expression
      was also strongly up-regulated by various abiotic stresses. CsHsp45.9 was mainly
      expressed in flowers with a flower-specific, stamen- and pistil-predominant
      expression pattern. This suggests that CsHsp45.9 harbors broad-spectrum responses
      to both biotic and abiotic stresses and may play a role in downy mildew
      resistance in cucumber.

PMID- 22367231
TI  - Gamete formation via meiotic nuclear restitution generates fertile amphiploid F1
      (oat*maize) plants.
AB  - Hybrid (oat*maize) zygotes developed into euhaploid plants with complete oat
      chromosome complements without maize chromosomes and into aneuhaploid plants with
      complete oat chromosome complements and different numbers of retained individual
      maize chromosomes. The elimination of maize chromosomes in the hybrid embryo is
      caused by uniparental genome loss during early steps of embryogenesis. Some of
      these haploid plants set seed in up to 50% of their self-pollinated spikelets.
      The high fertility was found to be mainly caused by formation of numerically
      unreduced female and male gametes (nunreduced=3x+0...3=21...24 chromosomes).
      Gamete formation involves meiotic nuclear restitution. The restitution process is
      caused by an alternative type of meiosis. It follows the model of levigatum-type
      semi-heterotypic divisions, but with a formation of the nuclear membrane at the
      transition from telophase I to interkinesis, which resembles the model of pygaera
      type pseudo-homotypic divisions. We propose the name haploid meiotic restitution
      for this particular process combination. We discuss the use and implications of
      the specific process of gamete formation in F1 (oat*maize) plants.

PMID- 22367230
TI  - Differential effects of polyploidy and diploidy on fitness of apomictic Boechera.
AB  - The co-occurrence of apomixis (asexual reproduction) and polyploidy in plants has
      been the subject of debate in regard to the origin and evolution of asexuality.
      In recent years, polyploidy has been postulated as a maintenance and
      stabilization factor rather than as a source of apomixis origin. It is assumed
      polyploidy facilitates the compensation for mutation accumulation, and hence, the
      rare occurrence of diploid apomixis indirectly supports this finding.
      Nevertheless, diploid apomicts exist and are successful, especially in the genus
      Boechera. While comparing phenotypic traits, fitness-related traits and apomixis
      penetrance between both diploid and triploid apomicts in the genus Boechera, it
      was expected to find trait variance that can be attributed to ploidy.
      Surprisingly, little trait variation could be assigned to ploidy, but rather
      trait variations were mainly genotype-specific. Additionally, it is shown that
      paternal contribution is very important for trait success, even though all
      offspring are genetically identical to the mother plant. This harbors
      implications for the introduction of apomixis into crop plants, considering the
      effects of paternal contribution during asexual reproduction. Nevertheless,
      polyploidy is an efficient way to buffer deleterious mutations, but the
      flexibility of diploid apomicts of the genus Boechera for rare sexual events
      contributes to their success in nature.

PMID- 22367232
TI  - Pollen tube development in two species of Trithuria (Hydatellaceae) with
      contrasting breeding systems.
AB  - Trithuria (Hydatellaceae; Nymphaeales) is unique among early-divergent
      angiosperms in that its species are extremely small and most have exceptionally
      short, annual life histories. Given the evolution of these extremes of size and
      development, we sought to understand whether post-pollination processes still
      varied predictably with breeding system in Trithuria. To address this question,
      we studied two Western Australian species, Trithuria austinensis (dioecious,
      obligately outcrossing) and Trithuria submersa (bisexual, highly selfing). To
      document developmental timing, carpels were hand-pollinated, collected at
      sequential time points, and examined with light and fluorescence microscopy. In
      both species, pollen tubes first entered ovules<1 h after pollination, but the
      pollen tube pathway of outcrossing T. austinensis was almost four times longer
      and its pollen tube growth rates were up to six times faster (<=2,166 vs. 321
      MUm/h) than those of T. submersa. T. austinensis also exhibited greater male
      investment, slower pollen germination, and greater pollen tube attrition. These
      differences in male gametophyte development are predicted for outcrossers versus
      selfers in phylogenetically derived angiosperms. These new data for Hydatellaceae
      reinforce the idea that an acceleration of pollen tube development occurred in
      the Nymphaeales stem lineage, before the origin of Hydatellaceae. We infer that a
      recent evolutionary transition to selfing in T. submersa has been accompanied by
      predictable modifications to reproductive development, which, because of the
      ancient relationship between Hydatellaceae and all other angiosperms, suggests
      that traits underlying the lability of flowering plant post-pollination biology
      were present early in their history.

PMID- 22367233
TI  - Development and evaluation of a sleep education program for older adults with
      dementia living in adult family homes.
AB  - OBJECTIVES: To investigate the feasibility of implementing a Sleep Education
      Program (SEP) for improving sleep in adult family home (AFH) residents with
      dementia, and the relative efficacy of SEP compared with usual care control in a
      pilot randomized controlled trial. PARTICIPANTS: Thirty-seven AFH staff
      caregivers and 47 residents with comorbid dementia and sleep disturbances.
      INTERVENTION: SEP consisted of four training sessions with staff-caregivers to
      develop and implement individualized resident behavioral sleep plans.
      MEASUREMENTS: Treatment fidelity to the SEP was assessed following the National
      Institutes of Health (NIH) Behavior Change Consortium model utilizing trainer
      observations and staff-caregiver reports. Resident sleep was assessed by wrist
      actigraphy at baseline, 1-month posttreatment, and 6-month follow-up. Caregiver
      reports of resident daytime sleepiness, depression, and disruptive behaviors were
      also collected. RESULTS: Each key area of treatment fidelity (SEP delivery,
      receipt, enactment) was identified, measured, and yielded significant outcomes.
      Staff-caregivers learned how to identify sleep scheduling, daily activity, and
      environmental factors that could contribute to nocturnal disturbances and
      developed and implemented strategies for modifying these factors. SEP decreased
      the frequency and disturbance level of target resident nocturnal behaviors and
      improved actigraphically measured sleep percent and total sleep time over the 6
      month follow-up period compared with the control condition. CONCLUSION: Results
      suggest behavioral interventions to improve sleep are feasible to implement in
      adult family homes and merit further investigation as a promising intervention
      for use with AFH residents with dementia.

PMID- 22367234
TI  - Reactivity of scandium terminal imido complexes towards metal halides.
AB  - Reactions of scandium terminal imido complexes with CuI and [M(COD)Cl](2) (M =
      Rh, Ir) show two interesting reaction patterns, and the formed heterobimetallic
      complexes have intriguing structural features and show promising catalytic
      properties.

PMID- 22367235
TI  - Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes.
AB  - T lymphocytes play a major role in counteracting cancer occurrence and
      development. Immune therapies against cancer are focused on eliciting a cytotoxic
      T cell response. This anticancer activity is related to a variety of mechanisms
      including the activation of cytokines and proapoptotic mediators. Interferon
      alpha is an established inhibitor of cancer cell growth. A clinical situation
      involving the coexistence of high interferon alpha levels and lymphocyte
      activation is the Aicardi-Goutieres syndrome, a progressive encephalopathy
      arising usually during the first year of life characterized by intracranial basal
      ganglia calcifications, leukodystrophy and microcephaly. Aicardi-Goutieres
      syndrome 1 mutation silences the TREX1 gene, a major endogenous nuclease. The in
      vitro study presented herein evaluates the efficacy of the TREX1 mutation in
      potentiating the anticancer properties of T cells. A TREX1-mutated lymphocyte
      cell line was derived from an Aicardi-Goutieres syndrome patient and co-cultured
      with neuroblastoma cells and vascular endothelial cells in the presence of
      interferon alpha. TREX1-mutated lymphocytes exerted marked inhibitory action on
      neuroblastoma cell growth. Cathepsin D was recognized by qPCR as the main
      mediator produced by TREX1-mutated lymphocytes involved in the inhibition of
      neuroblastoma cell growth. These effects were enhanced in the presence of
      interferon alpha. Similar inhibitory effects in cell growth were exerted by TREX1
      mutated lymphocytes towards vascular endothelial cell angiogenesis as evaluated
      on Matrigel. The results obtained provide evidence that mutations of the TREX1
      gene increase the capability of T-lymphocytes to inhibit growth of neoplastic
      neuronal cells and related angiogenesis.

PMID- 22367237
TI  - Behind the statistics: the ethnography of suicide in Palestine.
AB  - As part of the first anthropological study on suicide in the modern Arab world,
      statistics gathered from the Ramallah region of the West Bank in Palestine
      painted an apparently remarkably similar picture to that found in Western
      countries such as the UK and France. More men than women completed suicide, more
      women than men attempted suicide. Men used more violent methods such as hanging
      and women softer methods such as medication overdose. Completed suicide was
      higher in the older age range, attempted suicide in the younger. However,
      ethnographic fieldwork and detailed examination of the case studies and suicide
      narratives gathered and analysed within the cultural, political and economic
      contexts illustrated more starkly the differences in suicidal practices between
      Palestinian West Bank society of the 1990s and other regions of the world. The
      central argument of the paper is that although statistics tell a very important
      story, ethnography uncovers a multitude of stories 'behind the statistics', and
      thus helps us to make sense of both cultural context and subjective experience.

PMID- 22367236
TI  - Decision making in urological surgery.
AB  - CONTEXT: Non-technical skills are important behavioural aspects that a urologist
      must be fully competent at to minimise harm to patients. The majority of surgical
      errors are now known to be due to errors in judgment and decision making as
      opposed to the technical aspects of the craft. EVIDENCE ACQUISITION: The authors
      reviewed the published literature regarding decision-making theory and in
      practice related to urology as well as the current tools available to assess
      decision-making skills. Limitations include limited number of studies, and the
      available studies are of low quality. EVIDENCE SYNTHESIS: Decision making is the
      psychological process of choosing between alternative courses of action. In the
      surgical environment, this can often be a complex balance of benefit and risk
      within a variable time frame and dynamic setting. In recent years, the emphasis
      of new surgical curriculums has shifted towards non-technical surgical skills;
      however, the assessment tools in place are far from objective, reliable and
      valid. Surgical simulators and video-assisted questionnaires are useful methods
      for appraisal of trainees. CONCLUSION: Well-designed, robust and validated tools
      need to be implemented in training and assessment of decision-making skills in
      urology. Patient safety can only be ensured when safe and effective decisions are
      made.

PMID- 22367238
TI  - Ritual vicissitudes: the uncertainties of Singaporean suicide rites.
AB  - In this article, I examine how Singaporean Chinese families and funeral
      professionals work together to ritually manage the meaning and consequences of a
      death by suicide. While the now dated literature on Chinese mortuary practice
      emphasizes the formality and rigidity of death rituals, during fieldwork I noted
      many moments of confusion within ritual, moments of innovation, when relatives
      broke away from the already uncertain ritual script, and moments of deceit, when
      relatives conspired with funeral directors to hide the reason for a death.
      Through an examination of three funerals for suicide victims, including two cases
      in which the fact that the death was a suicide was hidden, I suggest that a focus
      on moments of confusion and of innovation paradoxically better captures the
      dynamism and efficacy of Chinese funeral rituals: here indeterminacy is
      indispensable to ritual form.

PMID- 22367239
TI  - A phase I/II, non-randomized, feasibility/safety and efficacy study of the
      combination of everolimus, cetuximab and capecitabine in patients with advanced
      pancreatic cancer.
AB  - BACKGROUND: Improvements in knowledge of molecular mechanisms in cancer are the
      basis for new studies combining chemotherapy with targeted drugs. Inhibition of
      the epidermal growth factor receptor (EGFR) by erlotinib or cetuximab has limited
      or no activity, respectively, in pancreatic cancer. The crosstalk between EGFR
      and mammalian target of rapamycin (mTOR) pathways is a potential mechanism of
      resistance; therefore we conducted a study to explore safety and efficacy of
      multiple pathway inhibition by cetuximab and everolimus in combination with
      capecitabine. METHODS: Safety and efficacy of fixed standard dose cetuximab in
      combination with various dose levels of everolimus (5-10 mg/day) and capecitabine
      (600-800 mg/m(2) bid, 2 weeks every 3 weeks) were investigated in a phase I/II
      study in patients with advanced pancreatic cancer. The primary endpoint was
      objective response. RESULTS: Sixteen patients were treated in the phase I part at
      two dose levels. Mucositis, rash and hand-foot syndrome were dose-limiting
      toxicities. Dose level 1 (everolimus 5 mg/day, capecitabine 600 mg/m(2) bid for 2
      weeks every 3 weeks and cetuximab 250 mg/m(2) weekly) was considered the maximum
      tolerated dose (MTD). Of 31 patients in the phase II part, partial response was
      documented in two patients (6.5%) and five (16.1%) had stable disease. Median
      overall survival was 5.0 months (CI 3.1-6.8). CONCLUSION: The schedule of
      capecitabine, everolimus and cetuximab resulted in considerable epidermal and
      mucosal toxicities and prevented escalation to optimal dose levels. Because of
      toxicity and low efficacy this treatment combination cannot be recommended for
      treatment in pancreatic cancer patients.

PMID- 22367240
TI  - Visualisation and characterisation of ageing induced changes of polymeric
      surfaces by spectroscopic imaging methods.
AB  - A polymeric resin material was chosen as the model system to visualise the ageing
      induced chemical surface changes with molecular spectroscopic imaging techniques
      and correlate these results to physical properties such as colour changes. The
      influence of light radiation, temperature and humidity on the polymeric surfaces
      was analysed by means of attenuated total reflection infrared imaging, Raman
      imaging spectroscopy and scanning electron microscopy. Samples were analysed
      before, during and after the weathering/ageing tests. From these combined data,
      the mechanisms for the damaging of the resin surface under the various
      environmental conditions (as applied in the accelerated ageing tests) were
      deduced. Photo-oxidative decay of the resin leading to a degradation of the
      uppermost surface layers as well as hydrolysis of the aged surface was
      identified. The combination of the spectral and spatial data as obtained from
      spectroscopic imaging with the morphological and elemental information of
      scanning electron microscopic mapping experiments turned out to be highly
      advantageous for the elucidation of ageing processes. A correlation between the
      molecular spectroscopic data and the results from the macroscopic colour
      difference measurements was found.

PMID- 22367241
TI  - Simultaneous quantitative analysis of letrozole, its carbinol metabolite, and
      carbinol glucuronide in human plasma by LC-MS/MS.
AB  - Letrozole is an efficient endocrine treatment of postmenopausal breast cancer,
      however, not all patients benefit from this treatment, and moreover, severe side
      effects like arthralgia frequently lead to discontinuation. To better understand
      inter-individual variability in drug response and side-effects, plasma analysis
      of steady-state concentrations of letrozole and its major metabolites is crucial.
      We developed a rapid, sensitive, and specific method for the simultaneous
      quantification of letrozole and its metabolites 4,4'
      (hydroxymethylene)dibenzonitrile (carbinol) and bis(4-cyanophenyl)methyl
      hexopyranosiduronic acid (carbinol-gluc) by UHPLC-ESI-MS/MS using in-house
      synthesized, stable isotope-labeled internal standards. Following solid-phase
      extraction in BondElut C18 96-well plates, the analytes were separated on a
      ZORBAX Eclipse XDB-C18 column (1.8 MUm, 4.6 * 50 mm) with a gradient of
      acetonitrile in 0.1% acetic acid in water and detected on a triple quadrupole
      mass spectrometer with electrospray ionization in the multiple reaction
      monitoring mode. Lower limits of quantification were 20, 0.2, and 2 nM for
      letrozole, carbinol, and carbinol-gluc, respectively. The assay has been
      validated according to FDA guidance and applied to the analysis of 20 plasma
      samples of postmenopausal breast cancer patients treated with 2.5 mg of letrozole
      per day. Mean plasma levels (+/-SD) were 366 +/- 173, 0.38 +/- 0.09, and 34 +/-
      12 nM for letrozole, carbinol, and carbinol-gluc, respectively. Our rapid and
      sensitive mass spectrometry based method enables future pharmacokinetic
      investigations of letrozole outcome.

PMID- 22367242
TI  - Diels-Alder derivatization for sensitive detection and characterization of
      conjugated linoleic acids using LC/ESI-MS/MS.
AB  - The utility of Diels-Alder derivatization with 4-phenyl-1,2,4-triazoline-3,5
      dione (PTAD) for liquid chromatography/electrospray ionization tandem mass
      spectrometry of conjugated linoleic acids (CLAs) was examined. PTAD rapidly
      reacted with the CLAs, and the resulting derivatives were highly responsive in
      electrospray ionization mass spectrometry operating in the positive-ion mode. The
      derivatives produced characteristic product ions during tandem mass spectrometry,
      which enabled the sensitive detection [limit of detection 18 fmol (signal-to
      noise ratio of 5)] and the identification of the conjugated diene position. The
      PTAD derivatization also significantly increased the reversed-phase liquid
      chromatography separation selectivity for the most biologically active CLA
      isomers: cis-9,trans-11-CLA and trans-10,cis-12-CLA. The PTAD derivatization was
      applied to analyses of food and biological samples; the major CLAs in milk and
      beef fat samples were successfully identified, and trace amounts of CLAs in human
      saliva were detected with a simple pretreatment and short analysis time.

PMID- 22367243
TI  - Biomolecule immobilization techniques for bioactive paper fabrication.
AB  - Research into paper-based sensors or functional materials that can perform
      analytical functions with active recognition capabilities is rapidly expanding,
      and significant research effort has been made into the design and fabrication of
      bioactive paper at the biosensor level to detect potential health hazards. A key
      step in the fabrication of bioactive paper is the design of the experimental and
      operational procedures for the immobilization of biomolecules such as antibodies,
      enzymes, phages, cells, proteins, synthetic polymers and DNA aptamers on a
      suitably prepared paper membrane. The immobilization methods are concisely
      categorized into physical absorption, bioactive ink entrapment, bioaffinity
      attachment and covalent chemical bonding immobilization. Each method has
      individual immobilization characteristics. Although every biomolecule-paper
      combination has to be optimized before use, the bioactive ink entrapment method
      is the most commonly used approach owing to its general applicability and
      biocompatibility. Currently, there are four common applications of bioactive
      paper: (1) paper-based bioassay or paper-based analytical devices for sample
      conditioning; (2) counterfeiting and countertempering in the packaging and
      construction industries; (3) pathogen detection for food and water quality
      monitoring; and (4) deactivation of pathogenic bacteria using antimicrobial
      paper. This article reviews and compares the different biomolecule immobilization
      techniques and discusses current trends. Current, emerging and future
      applications of bioactive paper are also discussed.

PMID- 22367244
TI  - New catalytic ultrasound method for derivatization of 11-nor-Delta9
      tetrahydrocannabinol-9-carboxylic acid in urine, with analysis by GC-MS/MS.
AB  - A new procedure is described for the derivatization by silylation of 11-nor
      Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) present in urine,
      followed by analysis using gas chromatography-tandem mass spectrometry. A
      conventional procedure for derivatization of the analyte was evaluated using two
      types of experimental design. A 2(3) factorial design considered the parameters
      temperature, reaction time, and the solvent/derivatization agent ratio. A central
      composite design (CCD) was applied to optimize the values of the significant
      variables. The optimum conditions were a reaction temperature of 50  degrees C, a
      reaction time of 30 min, and a BSTFA/acetone ratio of 40:20. The use of imidazole
      as a catalyst, together with ultrasonication, reduced the reaction time to 5 min
      and increased the efficiency of derivatization of THCCOOH, compared with the
      conventional method. The operating conditions of the tandem mass spectrometer
      were also optimized. The method was linear in the concentration range 1-50 ng mL(
      1) (R(2) = 0.9951). Intra- and inter-day precisions were 7.7-12.3% and 11.1
      13.9%, respectively, recoveries ranged between 91 +/- 8% and 101 +/- 12%,
      accuracy (as % bias) was between -11.7% and +0.7%, and limits of detection and
      quantification were 0.5 and 1.0 ng mL(-1), respectively.

PMID- 22367245
TI  - Quantitative determination of phosphatidylcholine hydroperoxides during copper
      oxidation of LDL and HDL by liquid chromatography/mass spectrometry.
AB  - 1-Palmitoyl-2-linoleoylphosphatidylcholine monohydroperoxide (PC 16:0/18:2-OOH)
      and 1-stearoyl-2-linoleoylphosphatidylcholine monohydroperoxide (PC 18:0/18:2
      OOH) were measured by liquid chromatography/mass spectrometry (LC/MS) using
      nonendogenous 1-palmitoyl-2-heptadecenoylphosphatidylcholine monohydroperoxide as
      an internal standard. The calibration curves for synthetic PC 16:0/18:2-OOH and
      PC 18:0/18:2-OOH, which were obtained by direct injection of the internal
      standard into the LC/MS system, were linear throughout the calibration range (0.8
      12.8 pmol). Within-day and between-day coefficients of variation were less than
      10%, and the recoveries were between 86% and 105%. The limit of detection (LOD)
      and the limit of quantification (LOQ) were determined using synthetic standards.
      The LOD (signal-to-noise ratio 3:1) was 0.01 pmol, and the LOQ (signal-to-noise
      ratio 6:1) was 0.08 pmol for both PC 16:0/18:2-OOH and PC 18:0/18:2-OOH. With use
      of this method, the concentrations of PC 16:0/18:2-OOH and PC 18:0/18:2-OOH in
      the lipoprotein fractions during copper-mediated oxidation were determined. We
      prepared oxLDL and oxHDL by incubating native LDL and native HDL from human
      plasma (n =  10) with CuSO(4) for up to 4 h. The time course of the PC 16:0/18:2
      OOH and PC 18:0/18:2-OOH levels during oxidation consisted of three phases. For
      oxidized LDL, both compounds exhibited a slow lag phase and a subsequent rapidly
      increasing propagation phase, followed by a gradually decreasing degradation
      phase. In contrast, for oxidized HDL, both compounds initially exhibited a prompt
      propagation phase with a subsequent plateau phase, followed by a rapid
      degradation phase. The analytical LC/MS method for phosphatidylcholine
      hydroperoxides might be useful for the analysis of biological samples.

PMID- 22367246
TI  - Protein-imprinted materials: rational design, application and challenges.
AB  - Protein imprinting is a promising tool for generating artificial biomimetic
      receptors with antibody-like specific recognition sites. Recently, protein
      imprinted materials, as potential antibody substitutes, have attracted much
      attention in many fields, for example chemical sensors, chromatographic
      stationary phases, and artificial enzymes, owing to their long-term storage
      stability, potential re-usability, resistance to harsh environment, and low cost.
      In this critical review, we focus our discussion on the rational preparation of
      protein-imprinted materials in terms of choice of template, functional monomer,
      crosslinker, and polymerization format. In addition, several highlighted
      applications of protein-imprinted materials are emphasized, not only in well
      known fields but also in some unique fields, for example proteomics and tissue
      engineering. Finally, we propose challenges arising from the intrinsic properties
      of protein imprinting, for example obtaining the template, heterogeneous binding,
      and extrinsic competition, for example immobilized aptamers.

PMID- 22367247
TI  - A hydrogel-based versatile screening platform for specific biomolecular
      recognition in a well plate format.
AB  - Precise determination of biomolecular interactions in high throughput crucially
      depends on a surface coating technique that allows immobilization of a variety of
      interaction partners in a non-interacting environment. We present a one-step
      hydrogel coating system based on isocyanate functional six-arm poly(ethylene
      oxide)-based star polymers for commercially available 96-well microtiter plates
      that combines a straightforward and robust coating application with versatile bio
      functionalization. This system generates resistance to unspecific protein
      adsorption and cell adhesion, as demonstrated with fluorescently labeled bovine
      serum albumin and primary human dermal fibroblasts (HDF), and high specificity
      for the assessment of biomolecular recognition processes when ligands are
      immobilized on this surface. One particular advantage is the wide range of
      biomolecules that can be immobilized and convert the per se inert coating into a
      specifically interacting surface. We here demonstrate the immobilization and
      quantification of a broad range of biochemically important ligands, such as
      peptide sequences GRGDS and GRGDSK-biotin, the broadly applicable coupler
      molecule biocytin, the protein fibronectin, and the carbohydrates N
      acetylglucosamine and N-acetyllactosamine. A simplified protocol for an enzyme
      linked immunosorbent assay was established for the detection and quantification
      of ligands on the coating surface. Cell adhesion on the peptide and protein
      modified surfaces was assessed using HDF. All coatings were applied using a one
      step preparation technique, including bioactivation, which makes the system
      suitable for high-throughput screening in a format that is compatible with the
      most routinely used testing systems.

PMID- 22367248
TI  - Validation of a multi-residue method for the determination of several antibiotic
      groups in honey by LC-MS/MS.
AB  - The presented multi-method was developed for the confirmation of 37 antibiotic
      substances from the six antibiotic groups: macrolides, lincosamides, quinolones,
      tetracyclines, pleuromutilines and diamino-pyrimidine derivatives. All substances
      were analysed simultaneously in a single analytical run with the same procedure,
      including an extraction with buffer, a clean-up by solid-phase extraction, and
      the measurement by liquid chromatography tandem mass spectrometry in ESI+ mode.
      The method was validated on the basis of an in-house validation concept with
      factorial design by combination of seven factors to check the robustness in a
      concentration range of 5-50 MUg kg(-1). The honeys used were of different types
      with regard to colour and origin. The values calculated for the validation
      parameters-decision limit CCalpha (range, 7.5-12.9 MUg kg(-1)), detection
      capability CCbeta (range, 9.4-19.9 MUg kg(-1)), within-laboratory reproducibility
      RSD(wR) (<20% except for tulathromycin with 23.5% and tylvalosin with 21.4 %),
      repeatability RSD(r) (<20% except for tylvalosin with 21.1%), and recovery
      (range, 92-106%)-were acceptable and in agreement with the criteria of Commission
      Decision 2002/657/EC. The validation results showed that the method was
      applicable for the residue analysis of antibiotics in honey to substances with
      and without recommended concentrations, although some changes had been tested
      during validation to determine the robustness of the method.

PMID- 22367249
TI  - On the recall of vestibular sensations.
AB  - Functional neuroimaging studies on the recall or imagination of a distinctive
      task in the motor network or of sensations in sensory systems (visual, acoustic,
      nociceptive, gustatory, and olfactory) demonstrated that the respective primary
      cortex is often involved in the mental imagery process. Our aim was to examine
      this phenomenon in the vestibular system using fMRI. Sixteen healthy subjects
      were asked to remember the feeling of a rotatory chair procedure in contrast to
      an identical situation at rest. Shortly afterwards they were asked to recall the
      vestibular experience in a 1.5-T scanner. The resulting activations were then
      compared with the responses of a galvanic vestibular control experiment and a
      rest condition. The vestibular recall showed significant bihemispheric
      activations in the inferior frontal gyri, the anterior operculum, the middle
      cingulate, the putamen, the globus pallidus, the premotor motor cortex, and the
      anterior insula. We found activations in regions known to play a role in spatial
      referencing, motor programs, and attention in the recall of vestibular
      sensations. But important known relay stations for the cortical processing of
      vestibular information showed neither relevant activations nor deactivations.

PMID- 22367250
TI  - A 3-dimensional digital atlas of the ascending sensory and the descending motor
      systems in the pigeon brain.
AB  - Pigeons are classic animal models for learning, memory, and cognition. The
      majority of the current understanding about avian neurobiology outside of the
      domain of the song system has been established using pigeons. Since MRI
      represents an increasingly relevant tool for comparative neuroscience, a 3
      dimensional MRI-based atlas of the pigeon brain becomes essential. Using multiple
      imaging protocols, we delineated diverse ascending sensory and descending motor
      systems as well as the hippocampal formation. This pigeon brain atlas can easily
      be used to determine the stereotactic location of identified neural structures at
      any angle of the head. In addition, the atlas is useful to find the optimal angle
      of sectioning for slice experiments, stereotactic injections and
      electrophysiological recordings. This pigeon brain atlas is freely available for
      the scientific community.

PMID- 22367252
TI  - What have we learned about loop diuretics in acute decompensated heart failure?
      The DOSE trial.

PMID- 22367251
TI  - Uteroplacental insufficiency alters rat hippocampal cellular phenotype in
      conjunction with ErbB receptor expression.
AB  - INTRODUCTION: Uteroplacental insufficiency (UPI) produces significant
      neurodevelopmental deficits affecting the hippocampus of intrauterine growth
      restricted (IUGR) offspring. IUGR males have worse deficits as compared with IUGR
      females. The exact mechanisms underlying these deficits are unclear. Alterations
      in hippocampal cellular composition along with altered expression of neural stem
      cell (NSC) differentiation molecules may underlie these deficits. We hypothesized
      that IUGR hippocampi would be endowed with altered neuronal, astrocytic, and
      immature oligodendrocytic proportions at birth, with males showing greater
      cellular deficits. We further hypothesized that UPI would perturb rat hippocampal
      expression of ErbB receptors (ErbB-Rs) and neuregulin 1 (NRG1) at birth and at
      weaning to account for the short- and long-term IUGR neurological sequelae.
      METHODS: A well-established rat model of bilateral uterine artery ligation at
      embryonic day 19.5 was used to induce IUGR. RESULTS: As compared with gender
      matched controls, IUGR offspring have altered hippocampal neuronal, astrocytic,
      and immature oligodendrocytic composition in a subregion- and gender-specific
      manner at birth. In addition, IUGR hippocampi have altered receptor type- and
      gender-specific ErbB-R expression at birth and at weaning. DISCUSSION: These
      cellular and molecular alterations may account for the neurodevelopmental
      complications of IUGR and for the male susceptibility to worse neurologic
      outcomes.

PMID- 22367253
TI  - Single inhaler maintenance and reliever therapy (SMART) in  general practice
      asthma management: where are we?

PMID- 22367256
TI  - Promotoras in mental health: a review of English, Spanish, and Portuguese
      literature.
AB  - Promotoras have worked in various areas of public health; however, there is a
      lack of understanding about their work in mental health. This article reviews the
      literature in 3 different cultures/languages (English, Spanish, and Portuguese)
      and aims to describe promotoras' roles, training, and interventions and their
      outcomes related to mental health activities. Results demonstrate that in
      different cultures/languages, promotoras empower community members to promote
      mental health and prevent exacerbation of individuals' mental illness.
      Promotoras, when trained carefully, have the ability to increase awareness and to
      promote mental health in populations that would otherwise have limited or no
      access to care.

PMID- 22367257
TI  - Diabetes and Healthy Eyes Toolkit: a community health worker program to prevent
      vision loss and blindness among people with diabetes.
AB  - Diabetic eye disease is a leading cause of vision loss and blindness in the
      United States and disproportionately affects Hispanics/Latinos. This article
      provides an overview of the Diabetes and Healthy Eyes Toolkit, a culturally and
      linguistically appropriate resource designed for community health workers to
      educate people with diabetes about eye health complications. The toolkit provides
      science-based, easy-to-understand information that can be used to conduct
      interactive, educational sessions about diabetes and eye health, the importance
      of comprehensive dilated eye examinations at least once a year for people with
      diabetes, and other ways to prevent vision loss and blindness.

PMID- 22367258
TI  - Salud Para Su Carozon--a Latino promotora-led cardiovascular health education
      program.
AB  - Salud Para Su Carozon is a culturally sensitive, community-based program to
      increase heart healthy knowledge and behaviors among Latinos. Promotoras were
      trained using a 10-session manual to teach participants from 7 communities about
      heart disease risk factors and skills to achieve heart healthy behaviors. In 435
      participants with pre-to-post self-reported data, there were increases in
      physical activity outside of work (57%-78%), heart health knowledge (49%-76%),
      and confidence in preparing heart healthy meals (66%-81%) (all Ps < .001).
      Results suggest that promotoras can provide effective health education to improve
      heart health risk behaviors in select Latino communities.

PMID- 22367259
TI  - Promotoras' roles in integrative validity and treatment fidelity efforts in
      randomized controlled trials.
AB  - Promotoras from the communities in which interventions are implemented can be
      effective contributors to validity and fidelity efforts. This article describes a
      48-week randomized controlled trial Madres para la Salud (Mothers for Health) and
      illustrates the use of promotoras as collaborative members of the research team
      to contribute to attaining integrative validity and treatment fidelity. Madres
      para la Salud implements a culturally tailored physical activity program to
      effect changes in body fat, systemic and fat tissue inflammation, and depression
      symptoms. The significance of Madres para la Salud treatment validity and
      fidelity processes includes cultural tailoring of a social support intervention,
      and a promotora model to incorporate initial and ongoing fidelity monitoring.

PMID- 22367260
TI  - Salud Si: a case study for the use of participatory evaluation in creating
      effective and sustainable community-based health promotion.
AB  - Participatory evaluation can be an essential tool for community-based
      organizations in tailoring programs to the needs of the populations they serve.
      This article provides a case study of Salud Si, a promotora-driven health
      promotion program designed to encourage physical activity, fruit and vegetable
      consumption, and stress reduction among Mexican American women. Through a
      partnership between a community health center and an academic institution, we
      describe how the participatory evaluation framework is applied over a 10-year
      period throughout the stages of program development, implementation, and
      sustainability. Partners used the results to identify the essential elements of
      the health promotion program.

PMID- 22367261
TI  - The Latino Migrant Worker HIV Prevention Program: building a community
      partnership through a community health worker training program.
AB  - There is limited information on the impact of the HIV/AIDS epidemic on Latino
      migrant workers (LMWs), although available data indicate that this community is
      being disproportionally affected. The need for prevention programs that address
      the specific needs of LMWs is becoming well recognized. HIV prevention
      interventions that train and employ community health workers are a culturally
      appropriate way to address the issues of community trust and capacity building in
      this community. This article describes the Latino Migrant Worker HIV Prevention
      Program and its efforts to train and engage community health workers in the
      prevention of HIV among LMWs in South Florida.

PMID- 22367262
TI  - A unique model of the community health worker: the MGH Chelsea Community Health
      Improvement team.
AB  - With current trends in legislation around the delivery of patient care, the role
      of a community health worker (CHW) is gaining growing and much deserved
      attention. However, a system needs to be built for any CHW program to be
      successful and sustainable. This article describes a unique approach to community
      health work at the Massachusetts General Hospital Chelsea HealthCare Center where
      a well-integrated CHW model provides support for everyone involved in patient
      care: patients, providers, the community at large, and the internal CHW staff.

PMID- 22367263
TI  - Reducing diabetes disparities through the implementation of a community health
      worker-led diabetes self-management education program.
AB  - Disparities in prevalence of type 2 diabetes and complications in underserved
      populations have been linked to poor quality of care including lack of access to
      diabetes management programs. Interventions utilizing community health workers
      (CHWs) to assist with diabetes management have demonstrated improvements in
      patient outcomes. Use of CHWs may be an effective model for providing care
      coordination and reducing disparities, but there is limited knowledge on how to
      implement this model on a large scale. This article describes how an integrated
      health care system implemented a CHW-led diabetes self-management education
      program targeting Hispanic patients and reports lessons learned from the first 18
      months of operation.

PMID- 22367264
TI  - Promotores de salud and community health workers: an annotated bibliography.
AB  - For underserved and disenfranchised communities in the United States, affordable,
      effective health care can be nearly inaccessible, which often leads to the
      exclusion of these communities from relevant medical information and care.
      Barriers to care are especially salient in minority communities, where language,
      traditions and customs, socioeconomics, and access to education can serve as
      additional roadblocks to accessing health care information and services. These
      factors have contributed to a national health disparity crisis that unnecessarily
      places some communities in a vulnerable position without adequate prevention and
      treatment opportunities. One solution to the exclusion some communities face in
      the health care system may be the promotores de salud (PdS)/community health
      worker (CHW), an approach to culturally competent health care delivery whose
      popularity in the mainstream health care system has been steadily growing in
      recent decades. Known by a wide variety of names and broad in the spectrum of
      health issues they address, the PdS/CHW serves as cultural brokers between their
      own community and the formal health care system and can play a crucial role in
      promoting health and wellness within their community. This annotated bibliography
      was created to educate the reader about the history, definition, key features,
      utility, outcomes, and broad potential of the CHW approach in a variety of
      populations. Intended to serve as a reference point to a vast body of information
      on the CHW/PdS approach, this document is a resource for those wishing to effect
      change in the disparities within the health care system, and to improve the
      access to, quality, and cost of health care for underserved patients and their
      communities. Promotores de Salud is a Spanish term that translates to Health
      Promoter. A female health worker may be referred to as a Promotora, a male as a
      Promotor, and the plural of both is Promotores. For the purposes of this
      bibliography, the terms community health worker and promotores de salud may be
      used interchangeably.

PMID- 22367265
TI  - Papules, arthralgia, dry mouth and dry eyes: a quiz. Diagnosis: Multicentric
      reticulohistocytosis.

PMID- 22367267
TI  - Using professionalism to support a culture of safety.

PMID- 22367266
TI  - Characterization of effector memory CD8+ T cells in the synovial fluid of
      rheumatoid arthritis.
AB  - Little is known about the cellular characteristics of CD8(+) T cells in
      rheumatoid arthritis (RA). We addressed this by investigating whether the
      frequency of the CD8(+) T cell subsets and their phenotypic characteristics are
      altered in the peripheral blood and synovial fluid (SF) from patients with RA. In
      this study, CD8(+) T cells, mainly CD45RA(-) effector memory (EM) CD8(+) T cells,
      were increased significantly in the SF, but not in the peripheral blood from RA
      patients, compared with healthy controls. The synovial EM CD8(+) T cells were
      activated phenotypes with high levels of CD80, CD86, and PD-1, and had a
      proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive
      cells were prone to apoptosis. In addition, EM CD8(+) T cells in the SF were less
      cytotoxic, as they expressed less perforin and granzyme B. In particular, the
      proportions of synovial fluid mononuclear cells that were CCR4(+)CD8(+) T cells
      and IL-4-producing CD8(+) T cells (i.e., Tc2 cells) were significantly higher
      than those in peripheral blood mononuclear cells of patients with RA and healthy
      controls. In addition, the number of IL-10-producing CD8(+) suppressor T (Ts)
      cells increased significantly in the SF of RA patients. Especially, CD8(+) T
      cells were inversely correlated with disease activity. These findings strongly
      suggest that EM CD8(+) T cells in the SF are increased, likely because of
      inflammation, and they may be involved in modulating inflammation, thereby
      affecting the development and progression of RA.

PMID- 22367268
TI  - Symptom clusters in women with relapsing-remitting multiple sclerosis.
AB  - The purpose of this secondary analysis was to investigate the relationships among
      a set of symptoms (fatigue, depression, impaired cognitive function, sleep
      disturbance) with pain severity and demographic variables. The sample of 40 women
      with relapsing-remitting multiple sclerosis completed instruments of pain,
      fatigue, depression, sleep disturbance, and an objective cognitive measure.
      Analysis identified one symptom cluster of pain, fatigue, depression, sleep
      disturbance, and impaired cognitive function, whereas a relationship between that
      symptom cluster and employment status existed. Pain severity correlated with
      fatigue, sleep disturbance, depression, and impaired cognitive function.
      Preliminary findings support providing education on symptoms to women with
      relapsing-remitting multiple sclerosis to ultimately guide their care.

PMID- 22367270
TI  - Dependence on care experienced by people living with Duchenne muscular dystrophy
      and spinal cord injury.
AB  - Being dependent on care in a hospital or in a traditional homecare setting may
      generate an experience of inferiority in patients. In a private home, dependence
      is easier to bear if the dependent person has the possibility to influence the
      planning of care. Little is known about the experience of being dependent on care
      in a private home, where the dependent person employs his or her own helpers. The
      aim of this study was to describe the meaning of dependence on care in a private
      home setting among people living with help requirements for all aspects of daily
      life. The article draws on two interview studies of people with high cervical
      spinal cord injury and men with Duschenne muscular dystrophy. Transcriptions of
      the interviews were analyzed according to a phenomenological hermeneutic approach
      influenced by Paul Ricoeur's philosophy of interpretation. The meaning of all the
      interview texts is presented as four short stories. Four themes were identified:
      the helper as liberating, the paramount verbalization of own needs, the creative
      engagement in life, and accessibility as an issue in everyday life. Dependence on
      care was identified to be a movement between freedom and restriction, where the
      helpers played a crucial role, because it was key that they were sensitive to the
      signals they got and were able to transform words into meticulous actions.

PMID- 22367269
TI  - Stroke survivor and informal caregiver perceptions of poststroke depressive
      symptoms.
AB  - Poststroke depression is common but remains underdiagnosed and undertreated. One
      explanation for this is that depressive symptoms go unrecognized by stroke
      survivors and their family caregivers and thus go unreported to the stroke
      survivor's healthcare provider. Forty-four stroke survivor-informal caregiver
      dyads were interviewed using a depression knowledge scale, the Center for
      Epidemiologic Studies Depression Scale, and an adapted version of the Revised
      Illness Perception Questionnaire to determine their lay knowledge of depressive
      symptoms, recognition of poststroke depressive symptoms, and perception of the
      recognized symptoms. Caregivers and stroke survivors had moderate knowledge of
      depressive symptoms but had some misconceptions. The most commonly recognized
      poststroke depressive symptoms by stroke survivors were "feeling like everything
      was an effort," "restless sleep," "difficulty concentrating," and "talking less
      than usual." Caregivers identified that the stroke survivor was "feeling like
      everything was an effort," had "restless sleep," "felt sad," and "felt
      depressed." Three quarters of stroke survivors with high levels of depressive
      symptoms identified the cluster of symptoms as potentially being depression.
      Neuroscience nurses are in the unique position to educate stroke survivors and
      their caregivers about poststroke depressive symptoms, treatment options, and the
      importance of discussing depressive symptoms with their healthcare provider.

PMID- 22367271
TI  - Nursing benefits of using an automated injection system for ictal brain single
      photon emission computed tomography.
AB  - The traditional method of administering radioactive isotopes to pediatric
      patients undergoing ictal brain single photon emission computed tomography
      testing has been by manual injections. This method presents certain challenges
      for nursing, including time requirements and safety risks. This quality
      improvement project discusses the implementation of an automated injection system
      for isotope administration and its impact on staffing, safety, and nursing
      satisfaction. It was conducted in an epilepsy monitoring unit at a large urban
      pediatric facility. Results of this project showed a decrease in the number of
      nurses exposed to radiation and improved nursing satisfaction with the use of the
      automated injection system. In addition, there was a decrease in the number of
      nursing hours required during ictal brain single photon emission computed
      tomography testing.

PMID- 22367273
TI  - The effect of low back pain on the daily activities of patients with lumbar disc
      herniation: a Turkish military hospital experience.
AB  - This study was performed to assess disability on daily living activities, which
      developed secondary to low back pain, in patients with lumbar disc herniation and
      treated either conservatively or surgically. The study was performed between
      November 2008 and June 2009. Visual analogue scale (VAS) was used to measure the
      intensity of pain, and the Oswestry Disability Index (ODI) was used to assess the
      disability of the patients on daily living activities. Of the 112 patients, 55
      were women and 57 were men. The mean age was 39.68 years for the conservative
      treatment group and 46.46 years the for surgical treatment group. In the
      pretreatment period, the patients who were selected for surgical treatment had
      higher VAS score and ODI than did the patients who were selected for conservative
      treatment. The disability areas that were reported in the pretreatment period
      were walking, sleeping, standing, and traveling for the surgical treatment group
      and self-care, sitting, and social life areas for the conservative treatment
      group. When the ODI and VAS score of the patients were statistically compared at
      the third month of posttreatment period, the scores were significantly low in the
      surgical treatment group. The disability areas that were reported at the third
      month of posttreatment period were weight lifting, self-care, and walking for the
      surgical treatment group and social life, sleeping, sitting, and standing for the
      conservative treatment group. This study found that patients with low back pain
      experience physical disabilities due to pain. Their daily living activities are
      affected by these disabilities and the intensity of pain affects the level of
      disability. Knowledge of the disability areas caused by low back pain plays an
      important role in the determination of nursing care and content of the education
      which will be offered to the patients. The use of scale on the patient's care is
      important to form a common language in nursing and to obtain evidence-based data
      related to the patients.

PMID- 22367274
TI  - Lessons learned in recruitment and retention of stroke survivors.
AB  - Recruitment and retention are considered among the most challenging steps in the
      research process. This becomes especially significant when the research
      population is stroke survivors with complex health needs and poststroke sequelae.
      The purpose of this article was to set forth and discuss challenges, barriers,
      and strategies in recruitment and retention of stroke survivors in a pilot study.
      This pilot study was carried out to assess the feasibility and effectiveness of
      problem-solving therapy for prevention and treatment of poststroke depression and
      for enhancement of quality of life, utilizing a randomized controlled design.
      Twenty-seven patients were recruited, and of those, 22 were retained and
      randomized to 2 groups. Treatment group participants (n = 11) received 10 weeks
      of problem-solving therapy by a trained nurse, and control group participants (n
      = 11) received 10 weeks of telephone calls only. Both groups were followed up to
      3 months after intervention completion. Careful field notes were recorded
      throughout the study to guide future larger scale studies. Challenges revolved
      around being accommodative to stroke survivors' schedules, establishing realistic
      inclusion and exclusion criteria, and providing incentives to the study
      participants in the control group. Recommendations include careful planning and
      organization of study procedures, soliciting feedback and support from physicians
      and administrative staff on the unit early in the process, developing a
      collaborative relationship with multidisciplinary staff, and continuously
      monitoring progress and implementing changes as needed.

PMID- 22367275
TI  - Clinical practice guideline series update.

PMID- 22367276
TI  - The effectiveness of a staff education program on the use of continuous EEG with
      patients in neuroscience intensive care units.
AB  - Approximately a third of patients in neuroscience intensive care units (ICUs)
      experience subclinical seizures and, as a result, are at higher risk for poor
      outcomes. The use of continuous electroencephalography (cEEG) monitoring can help
      nurses detect seizure activity and initiate early prevention. Nurse competency in
      the use of cEEG is important to facilitate effective bedside monitoring. The
      objective of this study was to evaluate the effectiveness of a staff educational
      program aimed at improving the knowledge of nurses in the use of cEEG monitoring
      in adults. A quasi-experimental pretest/posttest 1-group design was utilized.
      Neuroscience ICU registered nurses, whose experience ranged from 2 months to 24
      years, participated in the study. Participants completed a pretest on seizure
      knowledge and the use of cEEG monitoring. Participants received a 4-hour
      educational session on the use of cEEG monitoring. Immediately after the program
      and again 1 month later, they completed a posttest. Test scores improved
      significantly from pretest to the first posttest (t = -15.093, p < .001).
      Although there was a slight decline in the mean score from the posttest to the 1
      month follow-up, posttest scores were significantly better than the pretest score
      (t = -12.42, df = 44, p < .001). Whereas years of experience correlated
      positively to the pretest score, after the intervention, no such correlation was
      evident. The results demonstrated that an educational program improved the
      competency of nurses in the use of cEEG with adult patients in a neuroscience ICU
      and that this knowledge was sustained over time. Further research is needed to
      demonstrate the effectiveness of this intervention in other settings.

PMID- 22367277
TI  - Elevated frequency and function of regulatory T cells in patients with active
      chronic hepatitis C.
AB  - BACKGROUND: Regulatory T cells (Tregs) play a pivotal role in the persistence of
      hepatitis C virus infection. The aim of this study was to evaluate the frequency
      and function of Tregs in patients with chronic hepatitis C (CHC). METHODS: We
      enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH
      group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14
      age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+,
      CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence
      activated cell sorting (FACS). The frequency of Tregs was determined by
      calculating the percentage of CD4+CD25(high) T cells among CD4 T cells. CD127 and
      CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming
      growth factor (TGF)-beta and interleukin (IL)-10 in immunosuppressive assays were
      detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive
      abilities of Tregs were evaluated by measuring their ability to inhibit the
      proliferation of effector cells. RESULTS: Higher proportions of Tregs were found
      in the CH and PNALT groups compared with the HS group. The populations of CD127
      low/negative and CD45RA negative cells were higher in the CH group than in the
      PNALT group. The expressions of IL-10 and TGF-beta in the CH and PNALT groups
      were significantly higher than those in the HS group. In addition, the
      immunosuppressive ability of Tregs from the CH group was increased relative to
      that in the PNALT and the HS group. CONCLUSIONS: CHC patients, irrespective of
      liver function, had higher frequencies of Tregs than healthy subjects; however,
      only CHC patients with inflammation showed enhanced immunosuppressive function of
      Tregs.

PMID- 22367279
TI  - Annotation and analysis of malic enzyme genes encoding for multiple isoforms in
      the fungus Mucor circinelloides CBS 277.49.
AB  - Based on the newly-released genomic data of Mucor circinelloides CBS 277.49, we
      have annotated five genes encoding for malic enzyme: all code for proteins that
      contain conserved domains/motifs for malic acid binding, NAD(+) binding and
      NAD(P)(+) binding. Phylogenetic analysis for malic enzyme genes showed that genes
      ID 78524 and 11639 share ~80% amino acid identity and are grouped in cluster 1;
      genes ID 182779, 186772 and 116127 share ~66% amino acid identity are grouped in
      cluster 2. Genes ID 78524, 11639 and 166127 produce proteins that are localized
      in the mitochondrion, while the products from genes 182779 and 186772 are
      localized in the cytosol. Based on the comparative analysis published previously
      by Song et al. (Microbiology 147:1507-1515, 2001), we propose that malic enzyme
      genes ID 78524, 166127, 182779, 186772, 11639, respectively, represent protein
      isoforms I, II, III/IV, V, and VI.

PMID- 22367278
TI  - Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced
      liver injury in nutritional steatohepatitis.
AB  - BACKGROUND: The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is
      a key regulator for induction of hepatic antioxidative stress systems. We aimed
      to investigate whether activation of Nrf2 protects against steatohepatitis.
      METHOD: Wild-type mice (WT), Nrf2 gene-null mice (Nrf2-null) and Keap1 gene
      knockdown mice (Keap1-kd), which represent the sustained activation of Nrf2, were
      fed a methionine- and choline-deficient diet (MCDD) for 13 weeks and analyzed.
      RESULTS: In Keap1-kd fed an MCDD, steatohepatitis did not develop over the
      observation periods; however, in Nrf2-null fed an MCDD, the pathological state of
      the steatohepatitis was aggravated in terms of fatty change, inflammation,
      fibrosis and iron accumulation. In WT mice fed an MCDD, Nrf2 and antioxidative
      stress genes regulated by Nrf2 were potently activated in the livers, and in
      Keap1-kd, their basal levels were potently activated. Oxidative stress was
      significantly increased in the livers of the Nrf2-null and suppressed in the
      livers of the Keap1-kd compared to that of WT, based on the levels of 4-hydroxy-2
      nonenal and malondialdehyde. Iron accumulation was greater in the livers of the
      Nrf2-null mice compared to those of the WT mice, and it was not observed in Keap1
      kd. Further, the iron release from the isolated hepatocyte of Nrf2-null mice was
      significantly decreased. Sulforaphane, an activator of Nrf2, suppressed the
      pathological states and oxidative stress in the livers. CONCLUSIONS: Nrf2 has
      protective roles against nutritional steatohepatitis through inhibition of
      hepatic iron accumulation and counteraction against oxidative stress-induced
      liver injury. Nrf2 activation by pharmaceutical intervention could be a new
      option for the prevention and treatment of steatohepatitis.

PMID- 22367280
TI  - Improvement of D-lactate productivity in recombinant Escherichia coli by coupling
      production with growth.
AB  - Coupling lactate fermentation with cell growth was investigated in shake-flask
      and bioreactor cultivation systems by increasing aeration to improve lactate
      productivity in Escherichia coli CICIM B0013-070 (ackA pta pps pflB dld poxB adhE
      frdA). In shake-flasks, cells reached 1 g dry wt/l then, cultivated at 100 rpm
      and 42 degrees C, achieved a twofold higher productivity of lactic acid compared
      to aerobic and O(2)-limited two-phase fermentation. The cells in the bioreactor
      yielded an overall volumetric productivity of 5.5 g/l h and a yield of 86 g
      lactic acid/100 g glucose which were 66% higher and the same level compared to
      that of the aerobic and O(2)-limited two-phase fermentation, respectively, using
      scaled-up conditions optimized from shake-flask experiments. These results have
      revealed an approach for improving production of fermentative products in E.
      coli.

PMID- 22367281
TI  - Plasma ghrelin levels are closely associated with severity and morphology of
      angiographically-detected coronary atherosclerosis in Chineses patients with
      diabetes mellitus.
AB  - AIM: Low plasma ghrelin level was found to be associated with diabetes, and
      ghrelin was shown to inhibit pro-atherogenic changes in experimental models of
      atherosclerosis. The aim of this study was to investigate the relationship
      between plasma ghrelin levels and coronary atherosclerotic lesions in Chinese
      patients with diabetes. METHODS: Plasma ghrelin levels were measured using an
      ELISA kit. The severity of coronary artery disease (CAD) was determined via
      angiography. Composition of atherosclerotic plaques was detected via coronary CT
      angiography. RESULTS: A total of 178 patients with diabetes were recruited. Among
      the patients, 70 were diagnosed with acute coronary syndrome (ACS), 82 with
      stable angina pectoris (SAP) and 26 without coronary angiographic finding
      (controls). A negative correlation was found between ghrelin levels and the
      severity of the CAD, as determined via the Gensini score (r=-0.2434; P=0.0217).
      In diabetic patients with CAD and a complex lesion, the plasma ghrelin levels
      were significantly lower than in those with a simple lesion (ACS group: 3.81 +/-
      0.49 ng/mL vs 4.72 +/- 0.50 ng/mL, P<0.0001; SAP group: 4.21 +/- 0.52 ng/mL vs
      4.76 +/- 0.59 ng/mL, P=0.0397). Angiographically-detected complex lesion was an
      independent factor associated with ghrelin levels (adjusted beta coefficient=
      0.67, 95% CI -0.97 to -0.37, P<0.0001). CONCLUSION: Low plasma ghrelin level is
      closely related to angiographically-detected severity and the complex lesion
      morphology in Chinese diabetic patients with CAD.

PMID- 22367284
TI  - A general electron transfer reduction of lactones using SmI2-H2O.
AB  - Herein we describe a strategy for the selective, electron transfer reduction of
      lactones of all ring sizes and topologies using SmI(2)-H(2)O and a Lewis base to
      tune the redox properties of the complex. The current protocol permits
      instantaneous reduction of lactones to the corresponding diols in excellent
      yields, under mild reaction conditions and with useful chemoselectivity. We
      demonstrate the broad utility of this transformation through the reduction of
      complex lactones and sensitive drug-like molecules. Sequential electron transfer
      reactions and syntheses of deuterated diols are also described.

PMID- 22367283
TI  - Role of G protein-coupled receptors in inflammation.
AB  - G protein-coupled receptors (GPCRs) play important roles in inflammation.
      Inflammatory cells such as polymorphonuclear leukocytes (PMN), monocytes and
      macrophages express a large number of GPCRs for classic chemoattractants and
      chemokines. These receptors are critical to the migration of phagocytes and their
      accumulation at sites of inflammation, where these cells can exacerbate
      inflammation but also contribute to its resolution. Besides chemoattractant
      GPCRs, protease activated receptors (PARs) such as PAR1 are involved in the
      regulation of vascular endothelial permeability. Prostaglandin receptors play
      different roles in inflammatory cell activation, and can mediate both
      proinflammatory and anti-inflammatory functions. Many GPCRs present in
      inflammatory cells also mediate transcription factor activation, resulting in the
      synthesis and secretion of inflammatory factors and, in some cases, molecules
      that suppress inflammation. An understanding of the signaling paradigms of GPCRs
      in inflammatory cells is likely to facilitate translational research and
      development of improved anti-inflammatory therapies.

PMID- 22367285
TI  - Biological responses related to agonistic, antagonistic and synergistic
      interactions of chemical species.
AB  - The fact that the essential or toxic character of elements is species specific
      has encouraged the development of analytical strategies for chemical speciation
      over the last twenty years; indeed, there are now a great number of them that
      provide very good performance. However, biological systems are exposed to a
      complex environment in which species of elements can interact in a
      synergistic/antagonistic fashion. Thus, the metabolism of trace elements cannot
      be considered in isolation. On the other hand, biological systems are dynamic, so
      it is necessary to study the trafficking of species of elements between organs,
      tissues or cell compartments in order to decipher the biochemical processes of
      the interactions in which they are involved. Although the application of liquid
      chromatography-inductively coupled plasma-based "metallomics" methods in
      combination with organic mass spectrometry can provide much-needed insight, new
      analytical strategies are required to really understand the role of species of
      elements in biological systems and the mechanisms of their interactions. In the
      present paper, the interactions of the most widely studied elements in this
      context (Se, Hg and As) are discussed, as well as other important interactions
      between different elements.

PMID- 22367282
TI  - Orphan G protein-coupled receptors (GPCRs): biological functions and potential
      drug targets.
AB  - The superfamily of G protein-coupled receptors (GPCRs) includes at least 800
      seven-transmembrane receptors that participate in diverse physiological and
      pathological functions. GPCRs are the most successful targets of modern medicine,
      and approximately 36% of marketed pharmaceuticals target human GPCRs. However,
      the endogenous ligands of more than 140 GPCRs remain unidentified, leaving the
      natural functions of those GPCRs in doubt. These are the so-called orphan GPCRs,
      a great source of drug targets. This review focuses on the signaling transduction
      pathways of the adhesion GPCR family, the LGR subfamily, and the PSGR subfamily,
      and their potential functions in immunology, development, and cancers. In this
      review, we present the current approaches and difficulties of orphan GPCR
      deorphanization and characterization.

PMID- 22367286
TI  - Deuterium-labelled N-acyl-L-homoserine lactones (AHLs)--inter-kingdom signalling
      molecules--synthesis, structural studies, and interactions with model lipid
      membranes.
AB  - N-Acyl-L-homoserine lactones (AHLs) are synthesized by Gram-negative bacteria.
      These quorum-sensing molecules play an important role in the context of bacterial
      infection and biofilm formation. They also allow communication between
      microorganisms and eukaryotic cells (inter-kingdom signalling). However, very
      little is known about the entire mechanism of those interactions. Precise
      structural studies are required to analyse the different AHL isomers as only one
      form is biologically most active. Theoretical studies combined with experimental
      infrared and Raman spectroscopic data are therefore undertaken to characterise
      the obtained compounds. To mimic interactions between AHL and cell membranes, we
      studied the insertion of AHL in supported lipid bilayers, using vibrational sum
      frequency-generation spectroscopy. Deuterium-labelled AHLs were thus synthesized.
      Starting from readily available deuterated fatty acids, a two-step procedure
      towards deuterated N-acyl-L-homoserine lactones with varying chain lengths is
      described. This included the acylation of Meldrum's acid followed by amidation.
      Additionally, the detailed analytical evaluation of the products is presented
      herein.

PMID- 22367287
TI  - Advances and trends in the design, analysis, and characterization of polymer
      protein conjugates for "PEGylaided" bioprocesses.
AB  - In addition to their use as therapeutics and because of their enhanced
      properties, PEGylated proteins have potential application in fields such as
      bioprocessing. However, the use of PEGylated conjugates to improve the
      performance of bioprocess has not been widely explored. This limited additional
      industrial use of PEG-protein conjugates can be attributed to the fact that
      PEGylation reactions, separation of the products, and final characterization of
      the structure and activity of the resulting species are not trivial tasks. The
      development of bioprocessing operations based on PEGylated proteins relies
      heavily in the use of analytical tools that must sometimes be adapted from the
      strategies used in pharmaceutical conjugate development. For instance, to
      evaluate conjugate performance in bioprocessing operations, both chromatographic
      and non-chromatographic steps must be used to separate and quantify the resulting
      reaction species. Characterization of the conjugates by mass spectrometry,
      circular dichroism, and specific activity assays, among other adapted techniques,
      is then required to evaluate the feasibility of using the conjugates in any
      operation. Correct selection of the technical and analytical methods in each of
      the steps from design of the PEGylation reaction to its final engineering
      application will ensure success in implementing a "PEGylaided" process. In this
      context, the objective of this review is to describe technological and analytical
      trends in developing successful applications of PEGylated conjugates in
      bioprocesses and to describe potential fields in which these proteins can be
      exploited.

PMID- 22367288
TI  - Quantitative analysis of azaspiracids in Azadinium spinosum cultures.
AB  - Azaspiracids (AZAs) are secondary metabolites of Azadinium spinosum that can
      accumulate in shellfish and cause food poisoning when consumed. We describe here
      an analytical procedure for the determination of AZAs in cultures of A. spinosum
      with a focus on the formation of AZA methyl esters as artefacts during extraction
      and sample pre-treatment. A. spinosum cells were collected from bioreactor
      cultures using centrifugation or filtration. Different extraction procedures were
      evaluated for formation of methyl ester artefacts, yield, and matrix effects.
      Filtration of cultures using glass-fibre filters led to increased formation of
      methyl esters, and centrifugation is recommended for recovery of cells. The
      extraction solvent (methanol (MeOH), acetone, and acetonitrile (MeCN)) did not
      significantly affect the yield of AZAs as long as the organic content was 80% or
      higher. However, the use of MeOH as extraction solvent led to increased formation
      of methyl esters. AZA1 recovery over two successive extractions was 100% at the
      95% confidence level for acetone and MeOH. In standard-addition experiments, no
      significant matrix effects were observed in extracts of A. spinosum or Azadinium
      obesum up to a sample size of 4.5 * 10(9) MUm(3). Moreover, experiments carried
      out to clarify the formation and structure of methylated AZA analogues led to the
      description of two AZA methyl esters and to the correction of the chemical
      structures of AZAs29-32.

PMID- 22367289
TI  - Unsupervised unmixing of Raman microspectroscopic images for morphochemical
      analysis of non-dried brain tumor specimens.
AB  - Raman microspectroscopic imaging provides molecular contrast in a label-free
      manner with subcellular spatial resolution. These properties might complement
      clinical tools for diagnosis of tissue and cells in the future. Eight Raman
      spectroscopic images were collected with 785 nm excitation from five non-dried
      brain specimens immersed in aqueous buffer. The specimens were assigned to
      molecular and granular layers of cerebellum, cerebrum with and without scattered
      tumor cells of astrocytoma WHO grade III, ependymoma WHO grade II, astrocytoma
      WHO grade III, and glioblastoma multiforme WHO grade IV with subnecrotic and
      necrotic regions. In contrast with dried tissue section, these samples were not
      affected by drying effects such as crystallization of lipids or denaturation of
      proteins and nucleic acids. The combined data sets were processed by use of the
      hyperspectral unmixing algorithms N-FINDR and VCA. Both unsupervised approaches
      calculated seven endmembers that reveal the abundance plots and spectral
      signatures of cholesterol, cholesterol ester, nucleic acids, carotene, proteins,
      lipids, and buffer. The endmembers were correlated with Raman spectra of
      reference materials. The focus of the single mode laser near 1 MUm and the step
      size of 2 MUm were sufficiently small to resolve morphological details, for
      example cholesterol ester islets and cell nuclei. The results are compared for
      both unmixing algorithms and with previously reported supervised spectral
      decomposition techniques.

PMID- 22367290
TI  - Comparison of an in-house method and the commercial SepsityperTM kit for
      bacterial identification directly from positive blood culture broths by matrix
      assisted laser desorption-ionisation time-of-flight mass spectrometry.
AB  - The identification of bacteria directly from positive blood cultures using matrix
      assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF
      MS) is a new challenge to microbiologists. However, the protocols previously
      described are often difficult to implement in routine and comparisons are not
      always possible due to the variability of interpretative criteria. This study
      evaluated the analytical and practical performances of an in-house (IH) method,
      adapted from previous protocols, and the SepsityperTM kit (Bruker Daltonics,
      Bremen, Germany). Positive blood cultures from 63 different patients were
      prospectively evaluated by both methods. To enhance the sensitivity of these
      methods, lowered cut-offs were assessed and validated on 66 additional samples.
      The IH method produced 86.4% and 73.7% correct genus and species identifications,
      respectively, when using the lowered cut-offs of 1.4 and 1.6 for correct genus
      and species identifications. The SepsityperTM kit showed similar results (78.0%
      and 68.4% correct genus and species identification, respectively). However, the
      IH method is ten-fold less expensive than the commercial option (0.72 vs. 7.45
      <euro>/analysis) and its turnaround time is approximately 20 min versus the
      nearly 40 min required for the SepsityperTM kit, which includes an extraction
      step. Finally, the IH method was introduced twice-daily in our routine practice.

PMID- 22367291
TI  - Mesenchymal stem cell-tumor cell cooperation in breast cancer vasculogenesis.
AB  - Mesenchymal stem cells (MSCs) are able to acquire endothelial-like
      characteristics but their involvement in regulating MSC vasculogenesis is more
      complex. MSCs are able to express endothelial markers when cultured in
      endothelial growth medium (EGM), proving their differentiation into endothelial
      like cells. The aim of our study was to evaluate the capacity of the MCF-7 breast
      cancer cell line to stimulate the organization of regular MSCs and MSCs culture
      expanded in EGM (MSCEs) into capillary-like structures and to assess the
      involvement of tumor-derived VEGF. We seeded MSCs and MSCEs on Matrigel in a
      Transwell two compartment culture system in the presence of VEGF, MCF-7 cells or
      their conditioned medium (CM). Both MSCs and MSCEs were CD31-negative, either in
      culture conditions, or in the Transwell system. MSCs had a clear tendency to
      organize in clusters and to form capillary-like structures, in the presence of
      VEGF or MCF-7 cells. MSCEs had a similar behavior, but their tendency to organize
      in clusters was lower. Neither MSCs nor MSCEs organized into capillary-like
      structures in the presence of MCF-7 CM, yet the tendency to organize in clusters
      was stronger in the MSCs. Following exposure both to EGM-2 alone and to EGM-2
      supplemented with MSCs or MSCEs, the MCF-7 cells were present as adherent cells
      on the bottom of the lower wells, while the tendency to organize as single cells
      (and not in clusters) was more evident when MCF-7 cells were co-cultured with
      MSCs compared to the other conditions. Both breast cancer cells and VEGF
      stimulate MSCs and MSCEs to form capillary-like structures, indicating a role of
      tumor-derived VEGF in modulating their recruitment into sites of pathological
      vasculogenesis. Preconditioning MSCs in EGM influenced their pattern of
      organization into capillary-like structures, but the potential changes in the
      molecular marker profile for their 'switch' to the endothelial cell line remain
      to be evaluated.

PMID- 22367292
TI  - Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the
      expression of HIF-1alpha and P-gp in the human pancreatic carcinoma cell line
      PANC-1.
AB  - The aim of this study was to verify the inhibitory effects of epigallocatechin-3
      gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible
      factor 1 (HIF-1alpha) and multidrug resistance protein 1 (MDR1/P-gp) in the human
      pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of
      pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The
      human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic
      conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for
      indicated hours. The effects of EGCG on the mRNA or protein expression of HIF
      1alpha and MDR1 were determined by RT-PCR or western blotting. Cellular
      proliferation and viability assays were measured using Cell Counting Kit-8.
      Western blotting revealed that EGCG inhibits the expression of the HIF-1alpha
      protein in a dose-dependent manner, while RT-PCR showed that it does not have any
      effects on HIF-1alpha mRNA. In addition, EGCG attenuated the mRNA and protein
      levels of P-gp in a dose-dependent manner, reaching a peak at the highest
      concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a
      concentration- and time-dependent manner. The attenuation of HIF-1alpha and the
      consequently reduced P-gp could contribute to the inhibitory effects of EGCG on
      the proliferation of PANC-1 cells.

PMID- 22367293
TI  - Nodal involvement by cutaneous CD30-positive T-cell lymphoma mimicking classical
      Hodgkin lymphoma.
AB  - An association between classical Hodgkin lymphoma (cHL) and mycosis fungoides
      (MF) or lymphomatoid papulosis has been reported in the literature. However,
      there can be considerable morphologic and immunophenotypic overlap between cHL
      and nodal involvement by CD30-positive T-cell lymphoproliferative disorders (CD30
      T-LPD). To examine this potential association, biopsies from patients with a
      history of MF or primary cutaneous CD30-T-LPD and lymph node biopsies reported as
      either CD30-positive T-cell lymphoma (TCL) with Hodgkin-like cells or cHL were
      retrieved from the authors' institution. Of 11 cases identified, 10 were
      considered CD30-positive TCL with Hodgkin-like cells, whereas 1 was confirmed as
      cHL upon review. Five cases originally diagnosed as cHL were revised as CD30
      positive TCL. Cases of CD30-positive TCL with Hodgkin-like cells showed a male
      predominance (M:F, 4:1) with a median age of 53 years (range, 44 to 72 y). Nearly
      all patients (9/10) initially presented with skin lesions. In 7/10 patients the
      draining lymph node was involved, whereas in 3 cases this could not be confirmed.
      Tumor cells morphologically resembled Hodgkin/Reed-Sternberg cells; they were
      uniformly strongly positive for CD30, and CD15 was expressed in 9/10 (90%) cases.
      A T-cell derivation was confirmed by T-cell antigen expression (7/10) and clonal
      rearrangement of T-cell receptor genes (9/10). In 3 cases a common T-cell clone
      was identified in skin and lymph node. B-cell markers (CD20/PAX5) were
      consistently negative. In 1 case the diagnosis of cHL followed by lymphomatoid
      papulosis was confirmed, with Hodgkin/Reed-Sternberg cells expressing PAX5, CD30,
      and CD15. In situ hybridization studies for Epstein Barr virus were negative. We
      show that cHL is less often associated with MF and primary cutaneous CD30-T-LPD
      than previously thought and that the coexpression of CD30 and CD15 in these TCLs
      may lead to a mistaken diagnosis of cHL.

PMID- 22367294
TI  - IgG4-related sclerosing disease of the small bowel presenting as necrotizing
      mesenteric arteritis and a solitary jejunal ulcer.
AB  - Since first described in the mid 1990s, there has been burgeoning literature on
      IgG4-related sclerosing disease. The number of sites that may be involved is ever
      increasing, with the pancreas, salivary glands, and lymph nodes being the most
      commonly affected organs. There are no well-documented cases arising in the
      gastrointestinal tract. In this report, we present the first case to our
      knowledge of IgG4-related sclerosing disease involving the small bowel with a
      distinctly unusual clinicopathologic presentation. A previously well 46-year-old
      woman presented with a 2-year history of intermittent abdominal pain with recent
      worsening due to small bowel obstruction. Following imaging, which showed
      jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a
      segmental small bowel resection. The resected jejunum revealed an isolated,
      stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A
      transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall
      of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells
      were also identified in a mesenteric lymph node. The serum IgG4 level was
      elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an
      almost constant feature of this disease, arteritis is not described other than in
      the lung and aorta. In this report, we also discuss the diagnostic pitfalls and
      the differential diagnoses that should be considered when this condition arises
      in the gastrointestinal tract.

PMID- 22367295
TI  - Usual and unusual histologic patterns of high Gleason score 8 to 10
      adenocarcinoma of the prostate in needle biopsy tissue.
AB  - High Gleason score 8 to 10 adenocarcinoma is the most aggressive and potentially
      lethal form of prostate cancer. The 2005 International Society of Urological
      Pathology (ISUP)-modified Gleason grading scheme defines several gland
      arrangements of high Gleason grade patterns 4 and 5. The aim of this
      investigation was to quantitate the frequency of the ISUP-defined high Gleason
      grade patterns in needle biopsy tissue, to determine the common admixtures and to
      characterize patterns not presented in the 2005 ISUP report. For patients who
      underwent radical prostatectomy, we analyzed for association of specific high
      grade patterns in needle biopsy with extraprostatic extension in radical
      prostatectomy tissues. A total of 268 prostate needle biopsy cases with Gleason
      score of 8 to 10 were examined. A mean of 3.6 patterns (range, 1 to 8) were
      identified per case and only 12% of cases had a pure single pattern. Ill-defined
      glands with poorly formed lumina (at 57%) and fused microacinar glands (at 53%)
      comprised the predominant and most frequently admixed patterns. Single cells and
      single signet ring cells were present in 53% and 31% of cases, respectively.
      Additional patterns in order of frequency included cords (35%), cribriform glands
      (25%), sheets of cells (19%), chains (4%), glomeruloid (3%), comedonecrosis (2%),
      and hypernephromatoid (1 case=0.3%). Gleason score 8 to 10 carcinomas are
      typically extensive in needle core tissue, with a mean of 4.4 positive cores
      (range, 1 to 15 cores) per case. Only 14 cases (5%) had high-grade minimal
      carcinoma measuring <1 mm in needle core tissue. Gleason grade patterns not
      described in the 2005 ISUP report include single file growth, solid cylinders,
      and nested patterns. The single file pattern was present in 40% of cases, and the
      small solid nested pattern was detected in 24% of cases. One case displayed solid
      cylinders. Only the single file pattern was associated with extraprostatic
      extension at radical prostatectomy (P=0.005). These results show that the 2005
      ISUP-defined patterns of high Gleason score 8 to 10 prostatic adenocarcinoma can
      be stratified on the basis of frequency of occurrence in needle biopsy tissue.
      Three patterns not defined in the 2005 ISUP scheme have been characterized,
      including single file, nested, and solid cylinder arrangements. As aggressive and
      potentially lethal prostate cancer is most often of Gleason score 8 to 10, it is
      important for diagnostic recognition purposes to be aware of the frequency of
      various patterns encountered in high Gleason score 8 to 10 adenocarcinomas, the
      types of pattern admixtures, and the histomorphologic presentation of unusual
      patterns. We propose that Gleason grade assignments should incorporate single
      file, solid nested, and solid cylinder arrangements as high-grade pattern 5
      because of the absence of glandular luminal space formation.

PMID- 22367296
TI  - Chromophobe renal cell carcinoma:  the impact of tumor grade on outcome.
AB  - It has been reported that Fuhrman grading is not appropriate for chromophobe
      renal cell carcinoma (RCC). The objective of this study was to determine whether
      nucleolar grading and the recently described chromophobe RCC grading system by
      Paner and colleagues provide prognostic information. Pathologic features of 185
      patients with chromophobe RCC treated surgically between 1970 and 2006 were
      reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM
      groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer
      specific (CS) survival was estimated using the Kaplan-Meier method, and
      associations with CS survival were evaluated using Cox proportional hazard
      regression models. Twenty-three patients died from RCC at a mean of 3.0 years
      after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence
      interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15
      years after surgery. Univariate associations with CS survival included the 2010
      TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis,
      chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features
      remained significantly associated with CS survival after adjusting for the 2010
      TNM stage groupings. When the analysis was restricted to the 155 patients with
      nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping
      (I vs. II) was significantly associated with CS survival (P=0.03). Although the
      chromophobe RCC grading system described by Paner and colleagues and nucleolar
      grade are associated with CS survival in chromophobe RCC, they add no additional
      prognostic information once TNM stage and sarcomatoid differentiation are
      assessed.

PMID- 22367297
TI  - A distinct subset of atypical Spitz tumors is characterized by BRAF mutation and
      loss of BAP1 expression.
AB  - We recently reported that germline mutations in BAP1 cause a familial tumor
      syndrome characterized by high penetrance for melanocytic tumors with distinct
      clinical and histologic features. Melanocytic neoplasms in affected individuals
      harbored BRAF mutations, showed loss of BAP1 expression, and histologically
      resembled so-called "atypical Spitz tumors" (ASTs). ASTs are an ill-defined and
      probably heterogenous group of melanocytic tumors that display histologic
      features seen in both Spitz nevi and melanomas. Their biological behavior cannot
      be reliably predicted. In view of the histologic similarities of the familial
      tumors and ASTs, we hypothesized that a subset of ASTs might harbor genetic
      alterations seen in the familial tumors. To address this hypothesis, we analyzed
      32 sporadic ASTs for BRAF mutations and for BAP1 expression. Nine (28%) sporadic
      ASTs showed loss of BAP1 expression, of which 8 (89%) had concomitant BRAF
      mutations. Only 1 of the BAP1-positive ASTs (4%) had a BRAF mutation (P<0.0001).
      BRAF-mutated, BAP1-negative tumors were primarily located in the dermis and were
      composed entirely or predominantly of epithelioid melanocytes with abundant
      amphophilic cytoplasm and well-defined cytoplasmic borders. Nuclei were commonly
      vesicular and exhibited substantial pleomorphism and conspicuous nucleoli. The
      combination of BRAF mutation and loss of nuclear BAP1 expression thus
      characterizes a subset of ASTs with distinct histologic features. The typical
      morphology of these tumors and BAP1 immunohistochemistry provide pathologic clues
      that will enable accurate identification of this subset. Future studies are
      necessary to determine whether this subset has a predictable clinical behavior.

PMID- 22367298
TI  - A study of DeltaNp63 expression in lung non-small cell carcinomas.
AB  - Distinguishing between lung adenocarcinoma and squamous cell carcinoma is
      becoming increasingly important, given the different treatment regimens
      available. Although histologic subdivision between the two is generally not
      difficult in differentiated tumors, it can be challenging in poorly
      differentiated tumors and may require a panel of immunohistochemistry stains. The
      p63 gene encodes two different N-termini (TA and DeltaN). DeltaNp63 is
      selectively expressed in squamous cell carcinoma, whereas TAp63 is not restricted
      only to it. 4A4, a widely used anti-p63 antibody, identifies both isoforms and is
      expressed in about 15% of adenocarcinomas, and, although generally focal, its
      expression can be diffuse. In this study, a total of 150 lung adenocarcinomas and
      50 squamous cell carcinomas were immunostained by antibodies for p63 (4A4),
      DeltaNp63 (p40), and TTF-1 (8G7G3/1). Twenty-seven adenocarcinomas (18%) were
      positive for p63 to a variable extent, with diffuse reaction being seen in 13
      tumors (8.7%). p63 expression was seen in all subtypes of adenocarcinomas, except
      for the mucinous type. p40 was negative in all adenocarcinomas. All squamous cell
      carcinomas were diffusely positive for both p63 and p40. Four of 27 p63-positive
      adenocarcinomas were negative for TTF-1. p63 expression is not uncommonly seen in
      adenocarcinomas, whereas DeltaNp63 (p40) expression is specific for squamous cell
      carcinoma, with sensitivity comparable to that of p63 expression. Presence of p63
      positive cells in poorly differentiated lung adenocarcinoma may be erroneously
      interpreted as evidence of squamous cell differentiation. p40 appears to be a
      more reliable marker for squamous cell carcinoma.

PMID- 22367299
TI  - Basaloid squamous cell carcinoma of the penis with papillary features:  a
      clinicopathologic study of 12 cases.
AB  - There are 3 distinct variants of penile squamous cell carcinoma frequently
      associated with human papillomavirus (HPV): basaloid, warty-basaloid, and warty
      carcinomas. Considering the high incidence rates of penile cancer in some
      countries, a large international study was designed to evaluate the presence of
      HPV, its genotype distribution, and its association with histologic types of
      penile cancer. In this international review of >900 cases, we found a group of
      highly distinct papillary neoplasms composed of basophilic cells resembling
      urothelial tumors but frequently associated with HPV. Macroscopically, tumors
      were exophytic or exoendophytic. Microscopically, there was a papillomatous
      pattern of growth with a central fibrovascular core and small basophilic cells
      lining the papillae. Positivity for HPV was present in 11 of 12 tumors (92%).
      Single genotypes found were HPV-16 in 9 tumors and HPV-51 in 1 tumor. Multiple
      genotypes (HPV-16 and HPV-45) were present in another case. Overexpression of p16
      was observed in all cases. Uroplakin-III was negative in all cases. The
      differential diagnosis was with basaloid, warty-basaloid, warty, and papillary
      squamous cell carcinoma and with urothelial carcinomas. Local excision (4 cases),
      circumcision (3 cases), or partial penectomy (5 cases) were preferred treatment
      choices. Tumor thickness ranged from 1 to 15 mm (average, 7 mm). Two patients
      with tumors invading 11 and 15 mm into the corpus spongiosum developed inguinal
      nodal metastasis. Of 11 patients followed up (median 48 mo), 7 were alive with no
      evidence of metastatic disease, 3 died from causes other than penile cancer, and
      another died postoperatively. This morphologically distinct tumor probably
      represents a papillary variant of basaloid carcinomas (papillary-basaloid
      carcinomas). Unlike typical basaloid carcinomas, the overall prognosis was
      excellent. However, deeply invasive tumors were associated with regional nodal
      metastasis indicating a potential for tumor-related death.

PMID- 22367300
TI  - Cystic papillary pattern in pancreatic ductal adenocarcinoma:  a heretofore
      undescribed morphologic pattern that mimics intraductal papillary mucinous
      carcinoma.
AB  - INTRODUCTION: The prototypic pancreatic ductal adenocarcinoma shows small-caliber
      glands that are placed within an exuberant desmoplastic stromal reaction. A
      number of histologic patterns have been described, and the majority of these
      patterns are genetically and biologically related to conventional ductal
      adenocarcinomas. In this report we describe our experience with a heretofore
      undescribed histologic pattern of pancreatic adenocarcinoma that mimics
      intraductal papillary mucinous carcinoma, both morphologically and
      radiologically. METHODS: We identified 10 cases of pancreatic adenocarcinoma with
      large-caliber malignant glands and an intraluminal papillary pattern. The
      demographic, clinical, radiologic, and outcome data were recorded. In addition to
      a review of the histologic features we also performed elastin stains,
      immunohistochemistry for selected oncogenes and tumor suppressor genes including
      SMAD4. Immunohistochemical staining for MUC proteins was also performed. RESULTS:
      The median age of the patients was 67 years, and there were 6 women and 4 men.
      Grossly, the cut surface in 6 of these cases showed an admixture of solid and
      cystic areas. The papillary cystic architecture was intimately mixed with areas
      of conventional adenocarcinoma, the latter characterized by invasive small
      caliber tubular structures. None of the tumors showed a pure papillary cystic
      pattern; however, in 8 cases, this was the predominant pattern (>50% of the
      tumor). The cysts and papillae were lined predominantly by tall columnar
      hypermucinous epithelium. Elastin fibers were not identified around these dilated
      malignant cysts and glands. The intratumoral stroma was paucicellular and
      hyalinized. Seven of the 10 tumors were negative for SMAD4. The lack of
      pericystic elastin fibers and loss of SMAD4 in the majority of cases argue
      against these lesions representing an intraductal papillary mucinous neoplasm.
      All 10 tumors stained for MUC1; focal MUC2 reactivity was noted in 1 case. The
      majority of cases were positive for MUC5AC (9/10) and MUC6 (8/10). Seven patients
      died of their disease, whereas 1 patient is alive with widely metastatic disease.
      Two patients were lost to follow up. CONCLUSIONS: The adenocarcinoma described
      herein is a unique morphologic pattern of pancreatic ductal adenocarcinoma. The
      biology and genetics (as estimated by immunohistochemistry) are no different from
      that of conventional ductal adenocarcinoma but are distinctly different from that
      of an intraductal papillary mucinous carcinoma, its closest morphologic mimic.

PMID- 22367302
TI  - [Health Law section in the Gaceta Medica de Mexico].

PMID- 22367301
TI  - Digital fibromyxoma (superficial acral fibromyxoma):  a detailed characterization
      of 124 cases.
AB  - Digital fibromyxoma (first described by Fetsch and colleagues as superficial
      acral fibromyxoma) is a distinctive soft tissue tumor with a predilection for the
      subungual or periungual region of the hands and feet. This report details the
      histologic, immunophenotypic, and clinical findings in 124 cases of digital
      fibromyxoma. The study group included 70 male and 54 female patients (1.3:1,
      M:F), ranging in age from 4 to 86 years (mean, 48 y; median, 49 y). Mean tumor
      size was 1.7 cm (range, 0.5 to 5 cm; median, 1.5 cm). Nearly half of the patients
      (41%) presented with a painful mass. Tumors arose on the hands (52%) or feet
      (45%), with rare tumors arising on the ankle or leg. Most tumors occurred on the
      digits (94% of hand tumors, 82% of foot tumors), with the majority growing in
      close proximity to the nail (97% on fingers, 96% on toes). Histologically, 80% of
      cases were poorly marginated; 70% infiltrated the dermal collagen, 27%
      infiltrated fat, and 3% invaded bone. In cases in which imaging studies were
      available, bone involvement by an erosive or lytic lesion was more frequent
      (9/25, 36%). All tumors were composed of spindle-shaped or stellate-shaped cells
      with palely eosinophilic cytoplasm and a random or loosely fascicular growth
      pattern. The tumor cells were separated by dense hyaline collagen alternating
      with myxoid stroma. Most (86%) of the tumors showed alternating areas of fibrous
      and myxoid stroma, 11% showed predominantly fibrous stroma, and 3% had
      predominantly myxoid stroma. Increased mast cells were noted in 88% of tumors.
      All tumors comprised cells with minimal atypia, occasionally showing scattered
      larger cells with so-called "degenerative change." Mitotic figures were
      infrequent, and all tumors lacked necrosis, pleomorphism, or neural/perineural
      infiltration. Multinucleate stromal cells were occasionally seen. Tumor cells
      were reactive for CD34 in 42/61 cases (69%), with rare tumors showing focal
      reactivity for EMA (3/40, 7.5%), smooth muscle actin (5/42, 12%), and desmin
      (1/18, 6%). All tumors were negative for S100 (0/66), MUC4 (0/11), GFAP (0/10),
      AE1/AE3 (0/4), Cam5.2 (0/2), PanK (0/2), Claudin (0/4), and NFP (0/3). Follow-up
      in 47 cases ranged from 1 to 252 months (mean, 35 mo). Ten tumors (24%) recurred
      locally (all near the nail unit of the fingers or toes) after a mean interval of
      27 months. One tumor recurred twice. All recurrent tumors had positive margins on
      initial biopsy or subsequent excision and no other clinical or pathologic
      features correlated with recurrence/persistence. To date, no tumor has
      metastasized. Finally, sequencing of 8 digital fibromyxomas failed to reveal
      mutations in exon 8 or 9 of GNAS1, in contrast to intramuscular or cellular
      myxoma.

PMID- 22367303
TI  - [Cost-effectiveness of stress-only myocardial perfusion single photon emission
      computed tomography (SPECT) imaging].
AB  - Single photon emission computed tomography (SPECT) myocardial perfusion imaging
      is widely used for diagnosing coronary artery disease (CAD). However, SPECT
      costs, imaging time, and radiation exposure, limit SPECT indications. OBJECTIVE:
      Determine whether a stress-only SPECT imaging would be enough to obtain a
      diagnosis of CAD improving nuclear laboratory efficiency. METHODS: 122 patients
      with unknown CAD were evaluated with stress-only SPECT imaging. In order to
      evaluate diagnostic accuracy and the prognostic value of the stress-only
      protocol, patients with abnormal SPECT underwent invasive angiography and
      patients with normal SPECT were followed-up during 3 years. RESULTS: Diagnosis
      time, SPECT cost, and radiopharmaceutical dosage were significantly lower as
      compared with the conventional SPECT imaging protocol (30, 40 and 55%,
      respectively). Diagnostic accuracy and cardiac prognosis information were
      comparable to those obtained with the conventional imaging protocol (positive
      predictive value for CAD of 85% and negative predictive value for cardiac events
      of 97%). CONCLUSIONS: In patients with intermediate risk for CAD, stress-only
      SPECT imaging will significantly improve nuclear laboratory efficiency, and with
      similar accuracy than that the one obtained with the conventional protocol.

PMID- 22367304
TI  - [Prevalence of type 2 diabetes mellitus in elderly patients and associated
      factors in a general hospital of the north of Mexico].
AB  - There are few reports on the impact of diabetes in the geriatric population.
      OBJECTIVE: To determine the prevalence of diabetes in the geriatric population in
      a hospital in Northeast Mexico. DESIGN: A cross-sectional study and a
      probabilistic sampling were made. The files of outpatients of the geriatrics
      department in a General Hospital in Monterrey, Mexico,were examined. The
      information obtained from these files was related to the patient's personal
      pathological and non-pathological background, besides a full geriatric
      evaluation. RESULTS: A total of 171 files were examined, out of which 97 (56.7%)
      belonged to females and 74 (43.3%) to males. The mean age was 78 +/- 6.9 years.
      Diabetes was found in 76 patients (44%), major depression was found in 85
      patients (50%), with the latter being more common in diabetic patients (p =
      0.002). It was also found that diabetic patients take more drugs during their
      disease. Adjusting for age, gender, and academic level, cognitive impairment was
      found in 110 patients (64.3%). CONCLUSIONS: Diabetes mellitus is more frequent in
      the geriatric population and it uses more resources.

PMID- 22367305
TI  - [Risk factors associated to retinopathy of prematurity].
AB  - OBJECTIVES: To determine the most important risk factors for the incidence of
      retinopathy in premature infants. MATERIAL AND METHODS: A retrospective study,
      controls and cases of newborn infants (<= 32 weeks of gestation and birth weight
      <= 1,500) with diagnosis of retinopathy in the newborn intensive care unit were
      performed. RESULTS: Sixty cases of premature infants, with some grade of
      retinopathy, were found: 30 of which were male and 27 female.Three cases were
      excluded because of congenital problems. The two mainly involved risk factors in
      the retinopathy of neonates are gestational age (<= 28 weeks; p <= 0.001; OR:
      18.62; IC 95%: 7.36-47.09), and birth weight <= 1,000 g (p < 0.001; OR: 13.55; IC
      95%: 5.59-32.84). Other risk factors found were: hyaline membrane disease(HMD),
      late sepsis, frequent desaturations in newborns up to the second week of life
      related to apnea, surfactant and postnatal steroids administration, as well as
      more than 5 blood transfusions, or stay at hospital longer than 45 days.
      CONCLUSION: The two main risk factors in the onset of retinopathy in premature
      infants are gestational age and birth weight.

PMID- 22367306
TI  - [Gated single photon emission computed tomography (SPECT) and radionuclide
      ventriculography for evaluate the left ventricle ejection fraction in heart
      transplant recipients. Comparative study].
AB  - OBJECTIVE: To evaluate which is the best method to determine the left ventricular
      ejection fraction in heart transplant recipients: radionuclide ventriculography
      or gated SPECT, compared with echocardiography as the gold standard method.
      MATERIAL AND METHODS: A prospective, transversal, observational, and open study
      including all orthotopic heart transplant recipients between January 1, 1993 and
      December 31, 2010 was realized after signed Informed Consent, and we performed
      echocardiography, radionuclide ventriculography and gated SPECT in 14 patients.
      Normal value for left ventricle ejection fraction was considered 50% in all the
      methods. RESULTS: Fourteen heart transplant recipients were considered for the
      study. Two patients were excluded because of arrhythmic heartbeat at the time of
      gated SPECT acquisition and two by being newly transplanted. The mean left
      ventricle ejection fraction was: echocardiography: 69.9%;gated SPECT: 60%;
      radionuclide ventriculography: 61.1%. The sensitivity of gated SPECT was 75% and
      100% for radionuclide ventriculography. Specificity could not be obtained because
      our population was very small and there were no false negatives. (All the
      echocardiography results were over 50%). CONCLUSION: It was concluded that
      despite our small population, the gated SPECT was a useful tool in the evaluation
      of heart transplant patients due to its functional and prognostic information,
      besides offering myocardial perfusion imaging.

PMID- 22367307
TI  - [Severe periodontitis, edentulism and neuropathy in patients with type 2 diabetes
      mellitus].
AB  - Periodontitis is a frequent pathologic condition in diabetic patient, and has
      been associated with chronic complications like nephropathy, cardiovascular
      disease, peripheral artery disease or death. OBJECTIVE: To document the
      association between severe periodontitis and edentulism with the presence of
      sensory-motor neuropathy in diabetic patients. MATERIAL AND METHOD: Cross
      sectional study in type 2 diabetic patients from the family medicine unit no. 27
      of the IMSS in Tijuana, Mexico. Patients were evaluated to identify periodontitis
      and sensory-motor neuropathy. Information was also obtained about sex, age,
      duration of diabetes, glycemic control, smoking and alcohol use. RESULTS: Four
      hundred and thirty-six patients completed all measurements. In 180 (41.3%)
      neuropathy was identified, and associated with age (p < 0.001); duration of
      diabetes (p < 0.001); fasting glucose (p < 0.001); severe periodontitis (OR: 2.7;
      IC 95%: 1.5-4.8);and with edentulism (OR: 4.4; IC 95%: 2.0-9.4). Logistic
      regression multivariable analysis kept as significative the association between
      severe periodontitis and edentulism with neuropathy (adjusted OR: 1.7; IC 95%:
      1.1-2.6). CONCLUSIONS: Periodontitis and edentulism are associated with the
      presence of neuropathy in diabetic patients.

PMID- 22367308
TI  - [Mortality trends from cervical cancer in the seven socioeconomic regions and the
      thirty two federative entities of Mexico, 2000-2008].
AB  - OBJECTIVE: To determinate the trend of mortality from cervical cancer nationwide,
      by federative entities and socioeconomic regions during the years 2000-2008.
      METHODS: The records of mortality associated to cervical cancer for the period
      2000-2008 were obtained from the National Information System of the Secretariat
      of Health. This information is generated by the National Institute of Statistics
      Geography and Informatics through the death certificates issued all around the
      country. The codes of the international disease classification 10 that correspond
      to the basic cause of death from cervical cancer were identified. The rates of
      mortality nationwide, by federative entity and by socioeconomic region were
      calculated. Through Poisson regression analysis was compared mortality rates from
      cervical cancer of the socioeconomic regions and federative entities. The 7
      socioeconomic regions were elaborated by the National Institute of Statistics,
      Geography and Informatics and include the 32 federative entities according to
      indicators that are related to well-being such as education, occupation, health,
      housing and employment. RESULTS: The federative entities and socioeconomic region
      with the strongest association with mortality from cervical cancer in the period
      2000-2008 were Colima (RR: 1.67, IC 95%: 1.11-2.25 for the year 2000; RR: 1.92,
      IC 95%: 1.29-2.85 for the year 2008); Veracruz (RR: 1.85,IC 95%: 1.51-2.27 for
      2000; RR: 1.91, IC 95%: 1.55-2.35 for 2008); Yucatan (RR: 2.24, IC 95%: 1.74-2.88
      for 2000; RR:1.90, IC 95%: 1.44-2.49 for 2008); and region 1 (RR: 1.41, IC 95%:
      1.23-1.6 for 2001; RR: 1.38, IC 95%: 1.2-1.58 for 2007).In this region for the
      year 2000 and 2008 the RR was not statistically significant. CONCLUSIONS:
      Mortality rates per 100,000 women standardized using the world population
      decreased from 13.3 to 8.6 in the period 2000-2008. The entities and region with
      the strongest force of association with mortality due to cervical cancer were
      Colima, Veracruz,Yucatan and region 1.

PMID- 22367309
TI  - [The role of population genetics of Mexico in transplant immunology].
AB  - This review focuses on six transcendental aspects that affect transplant
      immunology in Mexico: in first place, several immune factors which may lead to
      graft loss are highlighted; then, some features of the biological variability
      present in Mexican populations are pointed out in the context of their adaptive
      and sociopolitical history, leading to the discussion on the genetic diversity
      within the major histocompatibility complex (MHC) and the importance of
      resolution in genotypic characterization of the human leukocyte antigen (HLA) and
      related systems on the basis of human intra-population variability. Critical
      points on the interpretation of serological reactivity of anti-HLA antibodies are
      discussed in function of allelic frequency as a probability of finding a variant
      in a finite population. Finally, evidence of influence of other genetic systems
      on the recipient-graft relationship is emphasized.

PMID- 22367310
TI  - [Neutrophil extracellular traps (NET), consequence of a cellular suicide].
AB  - Recently it was discovered that neutrophils can generate extracellular fibers
      called NET (neutrophil extracellular traps), which are composed of a skeleton of
      DNA "decorated" with many cytoplasmic -including enzymes- and nuclear
      components.The NET are a physical barrier that prevent the spread of
      microorganisms and facilitate the cell death by promoting a high local
      concentration of antimicrobial molecules. On the other hand, the fibrous
      structure limits the damage to the tissue where they are generated by restricting
      the range of molecules that are released by the neutrophil. This paper describes
      this new form of cell death and the implications this may have on different
      diseases.

PMID- 22367311
TI  - [Traumatic arteriovenous pial fistula masquerading as a carotid-cavernous
      fistula: an uncommon disorder with an unusual presentation].
AB  - Traumatic intracranial pial arteriovenous fistulae are infrequent lesions. Their
      cardinal signs have been related to mass effect and hemorrhage, but their
      clinical manifestations due to venous retrograde flow into ophthalmic veins has
      never been described. This phenomenon is usually seen in dural arteriovenous
      fistula draining to the cavernous sinus or carotid-cavernous sinus fistula.A
      traumatic intracranial pial arteriovenous fistula arising from the supraclinoid
      internal carotid artery in a young patient was revealed by aggressive behavior
      and ophthalmologic manifestations. The endovascular management included the use
      of coils, stent, and ethylene-vinyl alcohol with transient balloon occlusion of
      the parent vessel.

PMID- 22367312
TI  - [Yunis-Varon syndrome: a case report].
AB  - In 1980, Yunis-Varon described this disease. Yunis-Varon syndrome is a rare
      autosomal recessive disease. This cleidocranial dysplasia is characterized by
      bone and tooth disorders, in addition tends to affect the cardiovascular system
      and tissues from ectoderm. This report describes the radiologic image of a
      patient with Yunis-Varon syndrome.

PMID- 22367313
TI  - [Mexico recovers leadership on regulation of biosimilar biotech drugs].
AB  - Amid the epidemiological transition that Mexico is currently experiencing, an
      adequate access to biotech medicines is becoming very important. However, these
      medicines also involve new challenges for the sanitary authorities, given their
      higher complexity in structure and function than conventional chemical drugs.
      Consequently, it has been necessary to update the Mexican legal framework, which
      has placed Mexico at the forefront in this sector. This article describes briefly
      what biotech drugs are, why it has been necessary to regulate them differently,
      the evolution of the regulatory framework in Mexico, and the general features of
      the new system.

PMID- 22367314
TI  - [Neurorehabilitation: from a rigid past to a plastic future].
AB  - Since ancient times, several cultures including those from China, Egypt, India
      and Rome gave rigid solutions to improve physical problems of affected people by
      several neurological disorders. These measures were applied, at that time, by
      individuals prepared for doing such task. It evolved throughout the years
      supported by the discovery and comprehension of the so-called neural plasticity
      as well as the current evidences that the nervous system is able of remodelating
      itself even in adult times. It is known today that synaptic modulation is the
      base of neurorehabilitation improved by use and application of specific protocols
      to each neurological disorder. Among these, we have to consider not only all of
      the already known on rehabilitation measures but also on neurorobotic,
      neurorestauration, neuromodulation, neurostimulation as well as virtual reality,
      among others interventions. Neurorehabilitation has been able to put together
      modern science with ancient manual therapies helping to change, in a positive
      way, the attitude toward people with disabilities in the twenty one century;
      likewise, it offers new hopes for functional recovery where before was nothing.
      Further, it gives opportunities to get a better quality of life to affected
      people and its corresponding families. It is very interesting to know that the
      modern concepts of neurorehabilitation performed in a multidisciplinary approach
      are very useful for humans on the Earth and people interested in conquer Space.

PMID- 22367315
TI  - Proteasome inhibitor MG132 induces selective apoptosis in glioblastoma cells
      through inhibition of PI3K/Akt and NFkappaB pathways, mitochondrial dysfunction,
      and activation of p38-JNK1/2 signaling.
AB  - Proteasome inhibitors are emerging as a new class of anticancer agents. In this
      work, we examined the mechanisms underlying cytotoxicity, selectivity and
      adjuvant potential of the proteasome inhibitor MG132 in a panel of glioblastoma
      (GBM) cells (U138MG, C6, U87 and U373) and in normal astrocytes. MG132 markedly
      inhibited GBM cells growth irrespective of the p53 or PTEN mutational status of
      the cells whereas astrocytic viability was not affected, suggesting a selective
      toxicity of MG132 to cancerous glial cells. Mechanistically, MG132 arrested cells
      in G2/M phase of the cell cycle and increased p21(WAF1) protein immunocontent.
      Following cell arrest, cells become apoptotic as shown by annexin-V binding,
      caspase-3 activation, chromatin condensation and formation of sub-G1 apoptotic
      cells. MG132 promoted mitochondrial depolarization and decreased the
      mitochondrial antiapoptotic protein bcl-xL; it also induced activation of JNK and
      p38, and inhibition of NFkappaB and PI3K/Akt survival pathways. Pre-treatment of
      GBMs with the mitochondrial permeability transition pore inhibitor, bongkrekic
      acid, or pharmacological inhibitors of JNK1/2 and p38, SP600125 and SB203580,
      attenuated MG132-induced cell death. Besides its apoptotic effect alone, MG132
      also enhanced the antiglioma effect of the chemotherapeutics cisplatin, taxol and
      doxorubicin in C6 and U138MG cells, indicating an adjuvant/chemosensitizer
      potential. In summary, MG132 exerted profound and selective toxicity in GBMs,
      being a potential agent for further testing in animal models of the disease.

PMID- 22367316
TI  - The 3'-proximal part of the Plum pox virus P1 gene determinates the symptom
      expression in two herbaceous host plants.
AB  - Three major strains of the Plum pox virus (PPV) are the most important in Europe:
      PPV-D, PPV-M, and PPV-Rec. By combining the genomes of two different strains of
      PPV (PPV-D with PPV-Rec; PPV-D with PPV-M), 20 inter-strain chimeric infectious
      clones (CICPPV) were constructed. Biological properties of CICPPV were tested by
      inoculating them on different herbaceous host species susceptible to PPV. Four of
      the seven species tested, exhibited visible symptoms. In Nicotiana benthamiana
      all CICPPV induced systemic mosaic and leaf malformation. Pisum sativum showed a
      broad range of symptom severity (systemic chlorotic and necrotic lesions) but
      neither qualitative nor quantitative aspects of symptomatology were related to a
      single PPV genome locus. Nicotiana occidentalis and Nicandra physaloides proved
      to be suitable for symptom-based differentiation. Depending on the virus
      strain/chimera, N. occidentalis showed two types of symptoms: mild systemic
      chlorotic spots or local necrotic lesions/systemic vein necroses. N. physaloides
      reacted to the PPV infection either symptomless or by local necrotic lesions. Our
      results demonstrated that the P1/HC-pro region of the PPV genome appears to be
      the determinant of the symptom manifestation in these host plants. In silico
      analysis mapped it to the 3'-proximal part of the P1 gene.

PMID- 22367317
TI  - Polymorphisms of SPRN (shadow of prion protein homology) in three breeds of sheep
      in China.
AB  - The key point, which is related to the susceptibility of prion diseases in
      animals, has been proved to be the prion protein gene (PRNP). However, animals,
      especially sheep and goats, with the same PRNP genotype are not equally
      susceptible to the diseases. The finding of SPRN (shadow of prion protein
      homology) provides a new aspect to understand the diseases as protein of SPRN
      (Shadoo) has similar neuroprotective function and conserved hydrophobic core with
      prion protein (PrP). Researchers have made some efforts to demonstrate the
      relationship between SPRN and PRNP. Stewart's work has shown that SPRN contained
      an alanine-rich sequence, which is homologous to a hydrophobic core with
      amyloidgenic characteristics in PrP. Here our work shows that the sheep of Inner
      Mongolia in China have several haplotypes with the similar results of Stewart and
      Daude's. However we find a new haplotype in a Sunite sheep, which is not reported
      by others.

PMID- 22367318
TI  - In the current issue of our journal, we have included two manuscripts in which
      the association gynecologic cancer or precancerous lesions and breast cancer are
      discussed. Introduction.

PMID- 22367319
TI  - Increased expression of dachshund homolog 1 in ovarian cancer as a predictor for
      poor outcome.
AB  - OBJECTIVE: This study aimed to determine the functional relationship between the
      levels of dachshund homolog 1 (DACH1) expression and different subtypes of
      ovarian cancer and to investigate the possible prognostic value of DACH1 in
      ovarian cancer. METHODS: Immunohistochemical staining was deployed to determine
      the protein levels of DACH1. Staining was performed on patient samples, for whom
      the detailed follow-up data have been acquired during the last 10 years. Normal,
      benign, borderline, cancer, and metastatic ovarian cancer samples were included
      in this study. RESULTS: The results of our study show that DACH1 protein levels
      increase with the invasiveness of the ovarian cancer. As the cancer progresses
      from benign and borderline to metastatic, DACH1 protein expression increases as
      well. Moreover, with the increase in expression, the subcellular distribution of
      DACH1 changes from nucleus in normal tissue to cytoplasm in cancer. Finally,
      DACH1 expression levels were compared with estrogen receptor alpha (ERalpha)
      levels, and the results showed that overall DACH1 levels were higher, whereas
      also DACH1 exhibited increased cytoplasmic expression in ERalpha-positive ovarian
      cancer samples. CONCLUSIONS: These results indicate that DACH1 is highly
      expressed in metastatic ovarian cancer compared with that of normal, benign, and
      borderline ovarian tissues and that it could play an important role in cancer
      growth.

PMID- 22367320
TI  - Role of neoadjuvant chemotherapy in the management of stage IIIC-IV ovarian
      cancer: survey results from the members of the European Society of Gynecological
      Oncology.
AB  - OBJECTIVE: The aim of this study is to evaluate the current opinion of the
      members of the European Society of Gynecological Oncology (ESGO) on the use of
      neoadjuvant chemotherapy (NACT) in stage IIIC and IV ovarian cancer. METHODS: A
      link to a 21-item questionnaire, with questions about the management of patients
      with stage IIIC and IV ovarian cancer, was sent 3 times to the ESGO members (N =
      1177). RESULTS: Of the 469 (40%) responding members, 70.2% believe there is
      sufficient evidence to use NACT followed by interval debulking for the treatment
      of stage IIIC and IV ovarian cancer. On the basis of a multivariable logistic
      regression analysis, no relationships between the belief in evidence for NACT and
      practice type (P = 0.15) or level of experience (P = 0.41) were observed. Only
      5.3% of respondents never use NACT, and 30% uses NACT in less than 10% of their
      patients. Optimal debulking, defined as "no macroscopic residual tumor," is
      reported in more than 60% of the patients by 20% of the respondents at primary
      debulking, and by 34.6% of the respondents when interval debulking is performed.
      Whether a patient can be optimally primarily debulked is impossible to determine
      preoperatively according to 51.1% of the respondents. Computed tomographic scan
      (79.4%) and clinical examination (72.5%) are regarded as the most important
      modalities to predict operability. Diagnostic laparoscopy is used by 46.3% of the
      respondents. The most important reasons for choosing NACT are bulky disease in
      the upper abdomen (64.7%) and stage IV disease (58.7%). CONCLUSIONS: Of the
      responding ESGO members, 70% believe there is sufficient evidence to treat
      patients with stage IIIC-IV ovarian cancer with NACT, and 30% uses NACT in less
      than 10% of their patients.

PMID- 22367321
TI  - Laparoscopic versus abdominal approach to endometrial cancer: a 10-year
      retrospective multicenter analysis.
AB  - OBJECTIVE: The objective of this study was to give a reality-based picture of the
      use of laparoscopic surgery for staging endometrial cancer patients out of the
      experimental setting. METHODS: Consecutive data of patients with endometrial
      cancer who underwent laparoscopic or abdominal surgical staging in 6 Italian
      centers were recorded. Baseline patients and tumors characteristics, surgery
      performed, and safety data were collected and analyzed. RESULTS: A total of 1012
      subjects (403 and 609 treated by laparoscopy and laparotomy, respectively) who
      received surgical stadiation for endometrial cancer were included in the final
      analysis. The laparoscopic approach to endometrial cancer was more commonly
      performed in younger and nonobese patients who had received less previous
      surgeries, whereas the abdominal approach was preferred for the advanced stages
      and rare histotypes. Irrespectively to stage, the operative time was higher for
      the laparoscopy than laparotomy, whereas blood loss and postoperative
      complications were lower in the laparoscopy group than in the laparotomy group.
      No difference between surgical approaches was observed in complication rates in
      stage I endometrial cancers, whereas they were worst in higher stages. The site,
      but not the incidence, of recurrences differed only for advanced stage
      endometrial cancers. No differences in overall, disease-free, and cancer-related
      survival rates were also observed. CONCLUSIONS: In the clinical practice,
      heterogeneous criteria are adopted to recur to laparoscopy for staging
      endometrial cancer. The safety and the feasibility of the laparoscopy are
      confirmed for stage I endometrial cancers, whereas they appear suboptimal for the
      advanced stages.

PMID- 22367322
TI  - Prognostic value of the 2009 FIGO staging for endometrial cancer: an illustration
      of the E3N cohort.
AB  - OBJECTIVE: To compare the prognostic values of the 1988 and 2009 International
      Federation of Gynecology and Obstetrics (FIGO) classifications for endometrial
      cancer. MATERIALS AND METHODS: From 1990 to 2008, patients undergoing surgery for
      endometrial cancer were extracted from the French prospective "Etude
      Epidemiologique aupres de femmes de l'Education Nationale" cohort study.
      Inclusion criteria were as follows: (1) an available detailed histologic report
      of primary surgical procedure and (2) available cause and date of death.
      Concordance indexes for the 1988 and 2009 FIGO classifications were compared.
      RESULTS: Three hundred ninety-seven patients fulfilled the inclusion criteria.
      The concordance index for the 2009 FIGO classification was lower than that of the
      1988 FIGO classification (0.76 vs 0.77, respectively). CONCLUSION: In this study,
      the 1988 FIGO classification for endometrial cancer is at least as accurate as
      the 2009 FIGO classification for predicting endometrial cancer mortality.

PMID- 22367323
TI  - The prognostic significance of multiple pelvic node metastases in cervical cancer
      patients treated with radical hysterectomy plus adjuvant chemoradiotherapy.
AB  - OBJECTIVE: We investigated the prognostic significance of multiple pelvic node
      metastases in cervical cancer patients who were treated with radical hysterectomy
      plus adjuvant chemoradiotherapy. METHODS: We retrospectively reviewed the medical
      records of 311 patients with International Federation of Gynecology and
      Obstetrics stage IB1-IIB cervical cancer who had been treated with radical
      hysterectomy plus adjuvant radiotherapy (RT) between January 1998 and December
      2008. Of these, 119 received adjuvant RT and 192 received adjuvant concurrent
      chemoradiotherapy (CCRT) postoperatively. Multivariate analysis for progression
      free survival (PFS) was performed using the Cox proportional hazards regression
      model to investigate the prognostic significance of pelvic node metastases in the
      2 treatment groups. Survival was calculated using the Kaplan-Meier method and
      compared using the log-rank test. RESULTS: Multivariate analysis demonstrated
      pelvic node metastasis to be an independent prognostic factor for shorter PFS in
      both treatment groups. When the node-positive patients were analyzed according to
      the number of positive pelvic nodes, we found that the patients with multiple
      pelvic node metastases (>=3) displayed significantly shorter PFS than those with
      1 or 2 pelvic node metastases in the RT group. In contrast, in the CCRT group,
      the PFS of the patients with multiple pelvic node metastases (>=3) was similar to
      that observed of the patients with 1 or 2 pelvic node metastases. CONCLUSIONS:
      The presence of multiple pelvic node metastases was not an independent predictor
      of shorter PFS in the CCRT group.

PMID- 22367324
TI  - Validation of the FIGO 2009 staging system for carcinoma of the vulva.
AB  - BACKGROUND: The previous (1988) International Federation of Gynecology and
      Obstetrics (FIGO) vulval cancer staging system failed in 3 important areas: (1)
      stage 1 and 2 disease showed similar survival; (2) stage 3 represented a most
      heterogeneous group of patients with a wide survival range; and (3) the number
      and morphology of positive nodes were not taken into account. OBJECTIVE: To
      compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with
      regard to stage migration and prognostication. METHODS: Information on all
      patients treated for vulval cancer at the Queensland Centre for Gynecological
      Cancers, Australia, between 1988 to the present was obtained. Data included
      patients' characteristics as well as details on histopathology, treatments, and
      follow-up. We recorded the original 1988 FIGO stage, reviewed all patients'
      histopathology information, and restaged all patients to the 2009 FIGO staging
      system. Data were analyzed using the Kaplan-Meier method to compare relapse-free
      survival and overall survival. RESULTS: Data from 394 patients with primary
      vulval carcinoma were eligible for analysis. Patients with stage IA disease
      remained unchanged. Tumors formerly classified as stage II are now classified as
      stage IB. Therefore, FIGO 2009 stage II has become rare, with only 6 of 394
      patients allocated to stage II. Stage III has been broken down into 3 substages,
      thus creating distinct differences in relapse-free survival and overall survival.
      Prognosis of patients with stage IIIC disease is remarkably poor. CONCLUSION: The
      FIGO 2009 staging system for vulval carcinoma successfully addresses some
      concerns of the 1988 system. Especially, it identifies high-risk patients within
      the heterogeneous group of lymph node-positive patients.

PMID- 22367325
TI  - Two-port access versus conventional staging laparoscopy for endometrial cancer.
AB  - OBJECTIVE: The purpose of this study was to compare surgical outcomes of 2-port
      access (TPA) and conventional laparoscopy in staging operations for endometrial
      cancer. The ultimate goal of TPA system was to perform proper cancer operation
      with less invasive access and to complement technical limitations of minimally
      invasive surgery. METHODS: The TPA system consisted of a single multi-channel
      port system at the umbilicus and an ancillary 5-mm trocar in the suprapubic area.
      Twenty-one consecutive patients who underwent TPA staging laparoscopy for
      endometrial cancers were enrolled in the study. Data coming from this group of
      patients were prospectively collected and compared with those coming from 42
      consecutive patients who underwent conventional staging laparoscopy for the same
      period. The selected patients were matched (1:2 ratio) to control patients based
      on age (+/- 5 years), body mass index, and tumor stage. RESULTS: Patient status
      was estimated in operative morbidity and surgical outcomes. All operations were
      completed laparoscopically, with no conversion to laparotomy. The TPA group had a
      significantly longer operating time (238 +/- 51 minutes vs 188 +/- 65 minutes; P
      = 0.001), more retrieved para-aortic lymph nodes (13 vs 5; P < 0.001), shorter
      postoperative hospital stay (5 vs 8 days; P = 0.001), and less postoperative pain
      (P = 0.045). There were no postoperative complications requiring further
      management. CONCLUSIONS: Two-port access staging laparoscopy using a single multi
      channel port system could be a feasible procedure in selected patients with
      endometrial cancer with only minimal skin incisions. Prospective randomized
      trials will permit the evaluation of potential benefits of this minimally
      invasive surgical technique.

PMID- 22367326
TI  - Definitive radiotherapy for treatment of primary vaginal cancer: effectiveness
      and prognostic factors.
AB  - OBJECTIVE: This study was performed to evaluate treatment outcomes and define
      prognostic factors for primary vaginal cancer treated with definitive
      radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed 38 patients with
      primary vaginal cancer who received radiotherapy with curative intent between
      January 1981 and August 2008. Of these 38 patients, 6 were excluded from this
      analysis because of other uncontrolled malignancy (n = 1), uncommon histology (n
      = 4), or insufficient medical records (n = 1). Twenty-three patients (72%)
      presented with early-stage disease (International Federation of Gynecology and
      Obstetrics stages 0, I, or II). Eleven patients (34%) were treated with external
      beam radiotherapy (EBRT) alone and 21 patients (66%) with EBRT plus brachytherapy
      (BT). Low-dose rate cesium-137 was used with intracavitary technique for most of
      the patients who received BT. Five patients received chemotherapy. The median
      total dose in patients who received EBRT and EBRT+BT was 50.4 Gy (range, 39.6
      70.4 Gy) and 78.9 Gy (range, 72.0-87.0 Gy), respectively. RESULTS: The median
      duration of follow-up was 38 months. Five-year overall survival, cause-specific
      survival, disease-free survival, local control, and regional control rates for
      the analyzed patients were 75%, 88%, 58%, 62% and 90%, respectively. Thirteen
      patients had treatment failure as follows: local (n = 7), distant (n = 1), local
      plus regional (n = 1), local plus distant (n = 2), and local plus regional plus
      distant (n = 2). Primary tumor size was a significant prognostic factor for
      disease-free survival (P = 0.039). CONCLUSIONS: Definitive radiotherapy is an
      effective treatment modality for primary vaginal cancer. Local failure was the
      major failure pattern, and achievement of local control is important for disease
      control and survival.

PMID- 22367327
TI  - Mycorrhizal diversity and specificity in Lecanorchis (Orchidaceae).
AB  - Lecanorchis is a nonphotosynthetic plant genus in Vanilloideae, Orchidaceae.
      Because of the distribution of many Lecanorchis taxa in various climate
      conditions, we hypothesized that mycorrhizal diversity and specificity are
      different among the different taxa of Lecanorchis. In the present study,
      identities of mycorrhizal fungi were examined for 90 individuals of 10
      Lecanorchis taxa at 26 sites from Niigata to Okinawa Prefectures in Japan.
      Phylogenetic analyses of Lecanorchis taxa based on the internal transcribed
      spacer (ITS) region of the nuclear ribosomal RNA gene (rDNA) divided the examined
      Lecanorchis taxa into three groups, groups A, B, and C. ITS rDNA sequences
      suggested that fungi associating with Lecanorchis were ectomycorrhiza-forming
      fungi in Lactarius, Russula, Atheliaceae, and Sebacina, with Lactarius and
      Russula dominant. Our results suggested some degree of mycorrhizal specialization
      among Lecanorchis taxa. Interestingly, the Lecanorchis group C had some specific
      relationships with Lactarius, whereas less specificity was found in the
      relationships with Russula. However, observed specificity results may be biased
      by geographic opportunity, and we suggest further research to assess whether
      Lecanorchis species are limited to the associations we observed.

PMID- 22367329
TI  - Construction of a promoter-probe vector for Bacillus thuringiensis: the
      identification of cis-acting elements of the chiA locus.
AB  - The expression and application of Bacillus thuringiensis (Bt) chitinase genes
      have been extensively investigated. However, little information is available
      regarding the regulation of chitinase gene expression in Bt. In this study, a
      shuttle promoter-probe vector was constructed incorporating the thermostable beta
      galactosidase gene bgaB of B. stearothermophilus as the reporter for the study of
      Bt promoters. Using this plasmid, the activity of the chiA gene promoter in Bt
      was investigated. Deletion analysis of the putative chiA promoter region revealed
      that the sequence located ~75 bp DNA from positions -116 to -42, with respect to
      the translation start site, is the core promoter of chiA gene. Furthermore, a
      site for chitin induction was identified near position -36. This site for
      negative regulation was indicated downstream of the RNA polymerase binding sites
      of the promoter of chiA. The expression of chiA started in cell grown for about 6
      h and reached the maximum after 60 h of incubation. Induction of chiA expression
      by chitin was demonstrated by an increase in beta-galactosidase activity of ~2.5
      fold.

PMID- 22367330
TI  - Wonder and the clinical encounter.
AB  - In terms of intervening in embodied experience, medical treatment is wonder-full
      in its ambition and its metaphysical presumption; yet, wonder's role in clinical
      medicine has received little philosophical attention. In this paper, I propose,
      to doctors and others in routine clinical life, the value of an openness to
      wonder and to the sense of wonder. Key to this is the identity of the central
      ethical challenges facing most clinicians, which is not the high-tech drama of
      the popular conceptions of medical ethics but, rather, the routine of patients'
      undramatic but unremitting demands for the clinician's time and respectful
      attention. Wonder (conceived as an intense and transfiguring attentiveness) is a
      ubiquitous ethical source, an alternative to the more familiar respect for
      rational autonomy, a source of renewal galvanizing diagnostic imagination, and a
      timely recalling of the embodied agency of both patient and clinician.

PMID- 22367328
TI  - Current insights in invasive group A streptococcal infections in pediatrics.
AB  - A rising incidence of invasive group A Streptococcus infections (IGASI) has been
      noted in children in the past three decades. The relative frequency of the
      infection types showed marked differences to IGASI in adults, and severity of the
      disease resulted in a mortality rate usually comprising between 3.6% and 8.3%.
      The emm1-type group A Streptococcus (GAS) subclone displaying a particular
      pattern of virulence factors was widely disseminated and prevalent in children
      with IGASI while the emm3-type GAS subclone appeared as a recent emerging
      genotype. However, the implication of these hypervirulent clones in the increase
      of IGASI in children is still controversial. Recent advances in our knowledge on
      pathogenesis of IGASI underlined that deregulation of virulence factor
      production, individual susceptibility, as well as exuberant cytokine response are
      important factors that may account for the severity of the disease in children.
      Future changes in IGASI epidemiology are awaited from current prospects for a
      safe and effective vaccine against GAS. IGASI are complex infections associating
      septic, toxic, and immunological disorders. Treatment has to be effective on both
      the etiologic agent and its toxins, due to the severity of the disease associated
      to the spread of highly virulent bacterial clones. More generally, emergence of
      virulent clones responsible for septic and toxic disease is a matter of concern
      in pediatric infectiology in the absence of vaccination strategy.

PMID- 22367331
TI  - Felicitometric hermeneutics: interpreting quality of life measurements.
AB  - The use of quality of life (QOL) outcomes in clinical trials is increasing as a
      number of practical, ethical, methodological, and regulatory reasons for their
      use have become apparent. It is important, then, that QOL measurements and
      differences between QOL scores be readily interpretable. We study interpretation
      in two contexts: when determining QOL and when basing decisions on QOL
      differences. We consider both clinical situations involving individual patients
      and research contexts, e.g., randomized clinical trials, involving groups of
      patients. We note the ethical importance of such understanding: proper
      interpretation and communication facilitate health care decision making.
      Communication that facilitates interpretation is of moral significance since
      better communication can attenuate ethical problems and inform choices. Much of
      what is communication worthy about QOL assessments is determined by the
      particular QOL instrument used in the assessment and how it is administered. In
      practice, these choices will be driven by the purpose of the assessment, but, it
      is argued, to maximize understanding, we should combine the information garnered
      from traditional standardized QOL instruments, from individualized QOL
      assessments, and from a recently proposed dialogic paradigm, where QOL is
      determined by shared conversation regarding the interpretation of texts. And,
      while some studies can surely succeed using abbreviated methods of administration
      (e.g., postal surveys may suffice for certain purposes), we will focus on methods
      of administration involving interviewer-respondent interaction. We suggest that
      during the QOL elicitation process, interviewer and respondent should engage in a
      two-way conversation in order to achieve a shared understanding of the "answers"
      to QOL "questions" and, finally, to reach a shared interpretation of the
      individual's QOL.

PMID- 22367332
TI  - Determination of pharmaceuticals and antiseptics in water by solid-phase
      extraction and gas chromatography/mass spectrometry: analysis via
      pentafluorobenzylation and stable isotope dilution.
AB  - A sensitive yet robust analytical method is presented for the simultaneous
      determination of 12 human pharmaceuticals (valproic acid, phenytoin, ibuprofen,
      gabapentin, acetaminophen, gemfibrozil, naproxen, ketoprofen, secobarbital,
      phenobarbital, 5-fluorouracil, and diclofenac) and 6 antiseptics (biosol,
      biphenylol, p-chloro-m-cresol, p-chloro-m-xylenol, chlorophene, and triclosan).
      The method employs solid-phase extraction (SPE) followed by a novel
      pentafluorobenzylation using a mixture of acetontrile/water (1/1, v/v). The
      method is simple to perform (derivatization can be completed in a single test
      tube) and eliminates the need for any solvent/SPE cartridge drying or blow-down.
      It affords excellent resolution, high sensitivity and reproducibility, and
      freedom from interference even for matrices as complex as untreated sewage. The
      method was applied to the analysis of sewage samples using 15 isotopically
      labeled surrogates, which resulted in the detection of 10 of the 12
      pharmaceuticals and all of the antiseptics sought. Ten of 15 surrogates were
      synthesized from pure analytes by a simple H-D exchange reaction employing D(2)O
      and D(2)SO(4). Measured recoveries were sensitive to matrix effects and varied
      substantially among analytes, indicative of the limitations associated with using
      a single surrogate standard.

PMID- 22367333
TI  - Trace-element deficiencies in microvillous inclusion disease.

PMID- 22367334
TI  - Unconventional firepower:  an unexpected source of lead poisoning.

PMID- 22367335
TI  - Multiple duodenal ulcers: an unexpected finding in celiac disease.

PMID- 22367336
TI  - Endoscopic diagnosis of pediatric acute gastrointestinal graft-versus-host
      disease.
AB  - BACKGROUND AND OBJECTIVES: Acute graft-versus-host disease (GVHD) is a major
      cause of morbidity and mortality in the first 100 days following allogeneic
      hematopoietic progenitor stem cell transplant. The best diagnostic endoscopic
      strategy for gastrointestinal (GI) GVHD is a matter of debate. Our aim in the
      present study was to compare the relative contribution of the endoscopic
      appearance and biopsies from upper endoscopy and flexible sigmoidoscopy in
      children with suspected acute GVHD. METHODS: The present study was designed as
      single-center retrospective chart review cohort study. We reviewed the charts of
      all of the patients younger than 18 years with suspected acute GI GVHD who had
      endoscopic evaluation within the first 100 days after stem cell transplant
      between 1999 and 2009. RESULTS: A total of 48 patients were included. The most
      common symptoms prompting endoscopic evaluation were diarrhea (70%) and a
      combination of nausea and vomiting (67%). GVHD was diagnosed in at least 1 biopsy
      site in 40 of 48 patients (83%). Twenty-two of 40 (55%) patients with GVHD had
      simultaneous upper and lower endoscopic biopsies, 11 patients had only upper
      endoscopy, and 7 had only lower endoscopy. The most common endoscopic finding was
      normal mucosa. The sensitivity for diagnosing GVHD was 77% for both rectosigmoid
      and upper endoscopic biopsies. Thirty-three of 40 patients had upper endoscopy
      with biopsies; 28 (85%) had GVHD. The sensitivities and negative predictive value
      of gastric biopsies were 85% and 63%, whereas for duodenal biopsies they were 50%
      and 57%, respectively. CONCLUSIONS: Rectosigmoid and combined upper endoscopic
      biopsies are equally sensitive for the diagnosis of acute GI GVHD in children.
      Flexible sigmoidoscopy can be done unsedated in appropriate patients at the
      bedside without anesthesia; it can be performed first to identify GI GVHD.

PMID- 22367337
TI  - Cameron ulcer.

PMID- 22367338
TI  - Early high-dose amino acids for ELBW infants: too early and too much?

PMID- 22367339
TI  - Fatal Vibrio vulnificus sepsis in vertically acquired hepatitis C.

PMID- 22367340
TI  - Clinical applicability of the incidence of pediatric peptic ulcer bleeding in the
      United States.

PMID- 22367341
TI  - Is delivery by cesarean section a risk factor for persistence and severity in
      eosinophilic gastroenteropathy in pediatric patients?

PMID- 22367342
TI  - Risk factors for incidence of rotator cuff syndrome in a large working
      population.
AB  - OBJECTIVES: The aim of this study was to assess the effects of personal and work
      related factors on the incidence of rotator cuff syndrome (RCS) in a large
      working population. METHODS: A total of 3710 French workers were included in a
      cross-sectional study in 2002-2005. All completed a self-administered
      questionnaire about personal factors and work exposure. Using a standardized
      physical examination, occupational physicians established a diagnosis of RCS.
      Between 2007-2010, 1611 workers were re-examined. Associations between RCS and
      risk factors at baseline were analyzed by logistic regression. RESULTS: A total
      of 839 men and 617 women without RCS at baseline were eligible for analysis. RCS
      was diagnosed in 51 men (6.1%) and 45 women (7.3%). The risk of RCS increased
      with age for both genders [odds ratio (OR) 4.7 (95% confidence interval [95% CI]
      2.2-10.0) for men aged 45-49 years and 5.4 (95% CI 2.3-13.2) for women aged 50-59
      years; reference <40 years]. For men, the work-related risk factors were repeated
      posture with the arms above the shoulder level combined with high perceived
      physical exertion [OR 3.3 (95% CI 1.3-8.4)] and low coworker support [OR 2.0 (95%
      CI 1.1-3.9)]. For women, working with colleagues in temporary employment [OR 2.2
      (95% CI 1.2-4.2)] and repeated arm abduction (60-90 degrees ) [OR 2.6 (95% CI 1.4
      5.0)] were associated with RCS. CONCLUSIONS: Age was the strongest predictor for
      incident cases of RCS, and arm abduction was the major work-related risk factor
      for both genders. Lack of social support was a predictor for RCS among men.

PMID- 22367343
TI  - Azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT.

PMID- 22367344
TI  - Second allogeneic hematopoietic SCT for relapsed ALL in children.
AB  - A second SCT is generally accepted as the only potentially curative approach for
      ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL
      is not fully understood. We performed a retrospective analysis of 171 pediatric
      patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2
      years was 29.4 +/- 3.7%, the cumulative incidence of relapse was 44.1 +/- 4.0%
      and non-relapse mortality was 18.8 +/- 3.5%. Relapse occurred faster after the
      second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age
      (9 years or less), late relapse (180 days or more after first SCT), CR at the
      second SCT, and myeloablative conditioning were found to be related to longer
      survival. Neither acute GVHD nor the type of donor influenced the outcome of
      second SCT. Multivariate analysis showed that younger age and late relapse were
      associated with better outcomes. Our analysis suggests that second SCT for
      relapsed pediatric ALL is an appropriate treatment option for patients that have
      achieved CR, which is associated with late relapse after the first SCT.

PMID- 22367345
TI  - Donor-derived HLA antibody production in patients undergoing SCT from HLA
      antibody-positive donors.
AB  - Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched
      SCT have increasingly been recognized as a risk factor for primary graft failure.
      However, the clinical implications of the presence of HLA antibodies in donors
      remain unknown. We prospectively examined 123 related donors for the presence of
      HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57
      (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were
      HLA antibody-positive. Then, we determined the presence of HLA antibodies in
      seven patients who received SCT from antibody-positive donors. Of these, four
      became HLA antibody-positive after SCT. The specificities of the antibodies that
      emerged in the patients closely resembled those of the antibodies found in the
      donors, indicating their production by donor-derived plasma cells. Moreover, the
      kinetics of the HLA antibody levels were similar in all four patients: levels
      started increasing within 1 week after SCT and peaked at days 10-21, followed by
      a gradual decrease. These results suggest that donor-derived HLA antibody
      production frequently occurs in patients undergoing SCT from antibody-positive
      donors. Further studies are warranted for clarifying the clinical significance of
      donor-derived HLA antibodies, including the role of these antibodies in post
      transplant platelet transfusion refractoriness.

PMID- 22367347
TI  - miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells.
AB  - Periodontal ligament-associated protein-1 (PLAP-1/asporin) is a special marker in
      periodontal ligament tissue. It is an important regulator of osteogenic
      differentiation of periodontal ligament cells (PDLCs). This marker is also a
      prerequisite for periodontal ligament development and mineralization in
      maintaining homeostasis of the periodontium. However, the molecular mechanisms of
      the regulation of PLAP-1 expression at the post-transcriptional level remain
      unknown. By contrast, microRNAs (miRNAs) provide an additional level of
      regulation beyond that of transcription factors via regulation of the post
      transcriptional control of gene expression. This study was designed to analyze
      miRNA differential expression patterns of PDLCs at various osteoblastic
      differentiation stages and to determine the contribution of miRNAs in the
      regulation of PLAP-1 expression during osteoblast differentiation. Bioinformatic
      analysis was performed to predict miRNAs that potentially regulate the gene
      expression of PLAP-1. Dual luciferase reporter assay and qRT-PCR were performed
      to confirm the effects of these miRNAs on PLAP-1 gene expression. Our results
      indicated that mir-101 and mir-21 target PLAP-1 to regulate its expression during
      osteogenic differentiation of PDLCs.

PMID- 22367348
TI  - A nationwide study of acne treatment patterns in Korea: analysis of patient
      preconceived notions and dermatologist suggestion for treatment.
AB  - Patients often have preconceived notions about acne treatments before visiting
      dermatologists. The aim of this study was to explore the association between
      patients' beliefs regarding acne and physicians' suggestion for treatment
      modality in dermatology clinics. A cross-sectional, nationwide multicentre study
      was conducted. A total of 1,370 patients completed questionnaires about beliefs
      about acne treatment before seeking medical care, and 101 dermatologists assessed
      their acne severity and proposed treatment methods. We found that patients had
      preconceptions in understanding disease characteristics, assessing subjective
      acne severity and preferring specific treatment modalities. Dermatologists'
      determination of topical agents as first-line treatment was affected by disease
      severity and patients' preferences. They were also more likely to prescribe
      isotretinoin even in moderate acne compared to oral antibiotics and topical
      agents. Selections of physical treatments and light-based therapies were affected
      by patients' preferences, subjective self-evaluation and dermatologists'
      assessments. Thus, we suggest that acne treatment strategies should incorporate
      both patients' subjective perceptions and objective clinical practices into a
      management paradigm.

PMID- 22367349
TI  - A rational approach to assess volume status in patients with decompensated heart
      failure.
AB  - Although the past few decades have yielded significant improvements in the
      management of cardiomyopathy, heart failure remains a leading cause of
      hospitalization as well as readmissions, both in the United States and worldwide.
      Accurate assessment of volume status in these patients is of great importance
      because it guides initial therapies and aids in determining suitability for
      discharge. However, this assessment can prove to be challenging and, therefore,
      must be based on multiple data points and techniques. This review examines the
      various modalities of volume assessment in the patient with decompensated heart
      failure.

PMID- 22367350
TI  - Highly efficient synthesis of aromatic azos catalyzed by unsupported ultra-thin
      Pt nanowires.
AB  - Aromatic azos were synthesized using unsupported ultra-thin platinum nanowires as
      catalysts under mild reaction conditions and the reaction mechanism was proposed.

PMID- 22367351
TI  - Which antibiotics and breakpoints should be used for Aeromonas susceptibility
      testing? Considerations from a comparison of agar dilution and disk diffusion
      methods using Enterobacteriaceae breakpoints.
AB  - Aeromonas species are environmental organisms that are responsible for numerous
      infections in humans and animals. Their antimicrobial susceptibility is usually
      evaluated using Enterobacteriaceae breakpoints. Although disk diffusion and
      minimum inhibitory concentration (MIC)-based methods are important for infectious
      disease management and epidemiological surveys of resistance, comparisons between
      these two methods have not been extensively studied for Aeromonas isolates. We
      propose the first extensive comparison of agar dilution and disk diffusion
      susceptibility testing methods, performed for 20 antimicrobial agents, including
      unevaluated or incompletely evaluated antibiotics (ticarcillin with or without
      clavulanic acid, ertapenem, tigecycline), on 146 Aeromonas isolates affiliated
      with six Aeromonas species via molecular means. We evaluated the level of
      agreement between Enterobacteriaceae breakpoints-based methods. Reliable
      agreement (>95%) was observed for piperacillin, cefotaxime, cefepime, nalidixic
      acid, ofloxacin, ciprofloxacin, gentamicin, amikacin, tetracycline and
      cotrimoxazole, whereas marked inconsistencies between the methods were noted for
      carbapenems, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic
      acid, tobramycin and tigecycline. The results indicate that beta-lactam and
      aminoglycoside susceptibility testing should be limited to piperacillin, cephems,
      gentamicin and amikacin. Co-amoxiclav should be avoided given the lack of
      agreement between the two methods. Adjusting the zone diameter breakpoints for
      tigecycline and cefoxitin could also improve the agreement to >95% and reduce the
      error rates to acceptable levels.

PMID- 22367352
TI  - Gaining insight into the inhibition of glycoside hydrolase family 20 exo-beta-N
      acetylhexosaminidases using a structural approach.
AB  - One useful methodology that has been used to give insight into how chemically
      synthesized inhibitors bind to enzymes and the reasons underlying their potency
      is crystallographic studies of inhibitor-enzyme complexes. Presented here is the
      X-ray structural analysis of a representative family 20 exo-beta-N
      acetylhexosaminidase in complex with various known classes of inhibitor of these
      types of enzymes, which highlights how different inhibitor classes can inhibit
      the same enzyme. This study will aid in the future development of inhibitors of
      not only exo-beta-N-acetylhexosaminidases but also other types of glycoside
      hydrolases.

PMID- 22367353
TI  - N-acetyl peak in proton MR spectroscopy of metastatic mucinous adenocarcinoma of
      brain.

PMID- 22367354
TI  - Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery,
      and Therapeutic Outcome.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of
      pain associated with a variety of indications, including arthritic conditions,
      but their usefulness is often limited by dose-dependent adverse events (AEs),
      such as gastrointestinal disturbances, cardiovascular events, and renal toxicity.
      The risk of such effects could be reduced by the use of topical formulations,
      which offer the potential to deliver analgesic concentrations locally, at the
      site of inflammation, while minimizing systemic concentrations. The topical
      preparations currently approved in the United States are diclofenac sodium 1.5%
      topical solution (containing dimethyl sulfoxide as a penetration enhancer),
      diclofenac sodium gel 1%, and a diclofenac hydroxyethylpyrrolidine 1.3% patch.
      Each of these topical NSAIDs provide drug delivery to subcutaneous tissues for
      the management of pain associated with osteoarthritis or soft-tissue injuries.
      Furthermore, these formulations are not significantly associated with the
      systemic AEs associated with oral NSAIDs; the most common AEs associated with
      topical formulations are local skin reactions, which are usually mild and self
      limiting. Other topical NSAID preparations approved in the European Union include
      ibuprofen creams and gels, ketoprofen gel, felbinac gel and cutaneous foam, and
      piroxicam gel. Meta-analyses have confirmed the efficacy and safety of these
      preparations. However, it is important to recognize that pharmacokinetic
      absorption from topical formulations can vary markedly, even between different
      formulations of the same drug, depending on the agent, the underlying disorder,
      and the site of application. It is therefore essential to consider the patient,
      the drug, and the drug delivery mechanism when selecting a topical NSAID
      preparation. 

PMID- 22367355
TI  - Older people's preferences regarding programme formats for managing concerns
      about falls.
AB  - OBJECTIVE: to explore the preferences of community-dwelling older persons
      regarding different programme formats for managing concerns about falls. SUBJECTS
      AND DESIGN: cross-sectional study of 5,755 community-dwelling people aged >= 70
      years in the Netherlands. METHODS: a questionnaire assessed people's willingness
      to participate per programme format (n=6), i.e. a programme at home, via
      telephone, via home visits and telephone consultations, via television or via
      Internet. RESULTS: of the 2,498 responders, 62.7% indicated no interest in any of
      the formats. The willingness to participate per programme format varied between
      21.5 (at home) and 9.4% (via Internet). Among people interested in at least one
      of the formats (n=931), higher levels of fall-related concerns were associated
      with increased preference for a programme with home visits. Poor perceived health
      and age >= 80 years were associated with less preference for a group programme.
      Higher educated people were more in favour of a programme via Internet compared
      with their lower educated counterparts. CONCLUSION: the majority of community
      dwelling older people are not likely to participate in any of the six proposed
      programme formats for managing concerns about falls. However, when diverse
      formats of effective programmes will be made available, uptake and adherence may
      be increased since programme preferences are associated to specific population
      characteristics.

PMID- 22367356
TI  - Validation and diagnostic accuracy of the Alzheimer's questionnaire.
AB  - BACKGROUND: accurately identifying individuals with cognitive impairment is
      difficult. Given the time constraints that many clinicians face, assessment of
      cognitive status is often not undertaken. The intent of this study is to
      determine the diagnostic accuracy of the Alzheimer's questionnaire (AQ) in
      identifying individuals with mild cognitive impairment (MCI) and AD. METHODS:
      utilising a case-control design, 300 [100 AD, 100 MCI, 100 cognitively normal
      (CN)] older adults between the ages of 53 and 93 from a neurology practice and a
      brain donation programme had the AQ administered to an informant. Diagnostic
      accuracy was assessed through receiver-operating characteristic analysis, which
      yielded sensitivity, specificity and area under the curve (AUC). RESULTS: the AQ
      demonstrated high sensitivity and specificity for detecting MCI [89.00 (81.20
      94.40)]; [91.00 (83.60-65.80)] and AD [99.00 (94.60-100.00)]; [96.00 (90.10
      98.90)]. AUC values also indicated high diagnostic accuracy for both MCI [0.95
      (0.91-0.97)] and AD [0.99 (0.96-1.00)]. Internal consistency of the AQ was also
      high (Cronbach's alpha = 0.89). CONCLUSION: the AQ is a valid informant-based
      instrument for identifying cognitive impairment, which could be easily
      implemented in a clinician's practice. It has high sensitivity and specificity in
      detecting both MCI and AD and allows clinicians to quickly and accurately assess
      individuals with reported cognitive problems.

PMID- 22367357
TI  - Effect of vertebral fractures on function, quality of life and hospitalisation
      the AGES-Reykjavik study.
AB  - BACKGROUND: understanding the determinants of health burden after a fracture in
      ageing populations is important. OBJECTIVE: assess the effect of clinical
      vertebral and other osteoporotic fractures on function and the subsequent risk of
      hospitalisation. DESIGN: individuals from the prospective population-based cohort
      study Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were examined
      between 2002 and 2006 and followed up for 5.4 years. SUBJECTS: a total of 5,764
      individuals, 57.7% women, born 1907-35, mean age 77. METHOD: four groups with a
      verified fracture status were used; vertebral fractures, other osteoporotic
      fractures excluding vertebral, non-osteoporotic fractures and not-fractured were
      compared and analysed for the effect on mobility, strength, QoL, ADL, co
      morbidity and hospitalisation. RESULTS: worst performance on functional tests was
      in the vertebral fracture group for women (P < 0.0001) and the other osteoporotic
      fractures group for men (P < 0.05). Both vertebral and other osteoporotic
      fractures, showed an increased risk of hospitalisation, HR = 1.4 (95% CI: 1.3
      1.7) and 1.2 (95% CI: 1.1-1.2) respectively (P < 0.0001). Individuals with
      vertebral fractures had 50% (P < 0.0001) longer hospitalisation than not
      fractured and 33% (P < 0.002) longer than the other osteoporotic fractures group.
      CONCLUSION: individuals with a history of clinical vertebral fracture seem to
      carry the greatest health burden compared with other fracture groups, emphasising
      the attention which should be given to those individuals.

PMID- 22367358
TI  - Dysferlin-deficient immortalized human myoblasts and myotubes as a useful tool to
      study dysferlinopathy.
AB  - Dysferlin gene mutations causing LGMD2B are associated with defects in muscle
      membrane repair. Four stable cell lines have been established from primary human
      dysferlin-deficient myoblasts harbouring different mutations in the dysferlin
      gene. We have compared immortalized human myoblasts and myotubes carrying disease
      causing mutations in dysferlin to their wild-type counterparts. Fusion of
      myoblasts into myotubes and expression of muscle-specific differentiation markers
      were investigated with special emphasis on dysferlin protein expression,
      subcellular localization and function in membrane repair. We found that the
      immortalized myoblasts and myotubes were virtually indistinguishable from their
      parental cell line for all of the criteria we investigated. They therefore will
      provide a very useful tool to further investigate dysferlin function and
      pathophysiology as well as to test therapeutic strategies at the cellular level.

PMID- 22367359
TI  - Thoracolumbar scoliosis posterior approach.

PMID- 22367360
TI  - Malpractice litigation and the spine: the NHS perspective on 235 successful
      claims in England.
AB  - PURPOSE: The objective of this study was to evaluate the overall incidence and
      total burden of successful litigation relating to the management of spinal
      disease across the National Health Service (NHS) in England. METHODS: The study
      design comprised a retrospective review of the NHS Litigation Authority (NHSLA)
      database, retrieving all successful claims relating to spinal disease between
      2002 and 2010--a total of 235 (144 acute, 91 elective). RESULTS: The general
      trend for successful claims with relation to spinal surgery has actually been
      decreasing steadily over the last few years. The total value of these claims
      during the period was L 60.5 million, comprising L 42.8 million (L 28.6 million
      relating to acute diagnoses, L 16.1 million for elective) in damages and L 17.7
      million in legal costs (31% relating to NHS legal costs, the remainder claimants
      costs). CONCLUSIONS: Spinal litigation remains a source of significant cost to
      the NHS. The complexity of resolving these cases is reflected in the associated
      legal costs.

PMID- 22367361
TI  - Replication study for reported SNP associations with breast cancer survival.
AB  - PURPOSE: Nine previously reported associations between single nucleotide
      polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer
      Study (Stage 1) were further evaluated in relation to disease-free survival (DFS)
      and overall survival (OS) among 5,192 additional breast cancer patients (Stage
      2). METHODS: Hazard ratios (HR) and 95% confidence intervals (CI) were calculated
      by proportional hazards regression in models adjusted for age, disease stage,
      estrogen and progesterone receptor status, and treatment regimens. RESULTS: Two
      SNPs had generally consistent results and significant associations with OS in
      combined analyses. Compared to women with MMP7 rs11225297 AA genotypes, OS was
      moderately better for women with AT genotypes (HR: 0.8, 95% CI: 0.7-1.0) and much
      better for women with TT genotypes (HR: 0.4, 95% CI: 0.2-0.8). Compared to women
      with MMP8 rs11225395 CC genotypes, OS was slightly better for women with CT
      genotypes (HR: 0.9, 95% CI: 0.7-1.1) and moderately better for women with TT
      genotypes (HR: 0.6, 95% CI: 0.4-0.9). Joint analysis showed significant dose
      response relationships with increasing numbers of rare alleles for both OS (p <
      0.001) and DFS (p = 0.001). CONCLUSIONS: A functional variant in MMP8 and a SNP
      in high linkage disequilibrium with a functional variant in MMP7 were
      significantly associated with breast cancer survival in a large two-stage
      survival study among Chinese women. This supports the hypothesis that SNPs in
      matrix metalloproteinase genes may influence breast cancer prognosis; additional
      research on these and other SNPs in genes important in metastasis, angiogenesis,
      and the regulation of the tumor microenvironment is warranted.

PMID- 22367362
TI  - Which subgroup of patients with pathologic N2 non-small cell lung cancer benefit
      from surgery?
AB  - OBJECTIVE: Patients with pathologic N2 non-small cell lung cancer comprise a
      heterogeneous group. The objective of this study was to evaluate which subgroup
      of patients with pathologic N2 benefit from surgery in terms of survival
      probability. METHODS: This retrospective study included 141 patients who had
      undergone major resection with pathologically proven N2 from 1990 to 2006 (103
      with adenocarcinoma, 38 with squamous cell carcinoma). Patients undergoing
      preoperative induction therapy were excluded. Records were examined for age,
      gender, tumor size, surgical procedure, surgical side, clinical N status, primary
      tumor lobe, curative resection, and metastatic N2 stations. RESULTS: In patients
      with adenocarcinoma, surgical procedure, clinical N status, curative resection,
      and metastatic N2 stations were significant prognostic factors in univariate
      analysis. Age and curative resection were significant factors in patients with
      squamous cell carcinoma. In multivariate analysis, clinical N2 (P = 0.003),
      incomplete resection (P = 0.04), and multi-station N2 (P = 0.004) were
      significant adverse prognostic factors in patients with adenocarcinoma, whereas
      only incomplete resection (P = 0.002) was significant in patients with squamous
      cell carcinoma. For adenocarcinoma patients with pathologic N2, the 5-year
      survival rates were 58.8% for clinical N0-1 and single-station N2, 50% for
      clinical N2 and single-station N2, 23.9% for clinical N0-1 and multi-station N2,
      and 0% for clinical N2 and multi-station N2. CONCLUSIONS: Prognosis of patients
      with pathologic N2 can be grouped according to clinical N status and metastatic
      N2 stations in adenocarcinoma, but not in squamous cell carcinoma. Only
      adenocarcinoma patients with pathologic N2 appear to have heterogeneous subgroups
      with different prognoses.

PMID- 22367364
TI  - The New Bedford Harbor Superfund site long-term monitoring program (1993-2009).
AB  - New Bedford Harbor (NBH), located in southeastern Massachusetts, was designated
      as a marine Superfund site in 1983 due to sediment contamination by
      polychlorinated biphenyls (PCBs). Based on risks to human health and the
      environment, the first two phases of the site cleanup involved dredging PCB
      contaminated sediments from the harbor. Therefore, a long-term monitoring program
      (LTM) was developed to measure spatial and temporal chemical and biological
      changes in sediment, water, and biota to assess the effects and effectiveness of
      the remedial activities. A systematic, probabilistic sampling design was used to
      select sediment sampling stations. This unbiased design allowed the three
      segments of the harbor to be compared spatially and temporally to quantify
      changes resulting from dredging the contaminated sediments. Sediment was
      collected at each station, and chemical (e.g., PCBs and metals), physical (e.g.,
      grain size), and biological (e.g., benthic community) measurements were conducted
      on all samples. This paper describes the overall NBH-LTM approach and the results
      from the five rounds of sample collections. There is a decreasing spatial
      gradient in sediment PCB concentrations from the northern boundary (upper harbor)
      to the southern boundary (outer harbor) of the site. Along this same transect,
      there is an increase in biological condition (e.g., benthic community diversity).
      Temporally, the contaminant and biological gradients have been maintained since
      the 1993 baseline collection; however, since the onset of full-scale remediation,
      PCB concentrations have decreased throughout the site, and one of the benthic
      community indices has shown significant improvement in the lower and outer harbor
      areas.

PMID- 22367365
TI  - Valuing biodiversity attributes and water supply using choice experiments: a case
      study of La Campana Penuelas Biosphere Reserve, Chile.
AB  - The main objective of this study is to assess public economic preferences for
      biodiversity conservation and water supply and to analyse the factors influencing
      those preferences. A survey based on the choice experiment method was carried out
      at Penuelas National Reserve, Chile, an area that is threatened by both
      occasional forest fires and the growing housing market. The input of local
      administrators was used to define environmental attributes of the area related to
      biodiversity conservation and water supply. Attributes were selected for analysis
      by the choice experiment. The selected attributes were the following: existence
      of endemic orchid species, chances of observing animals with scenic attraction,
      additional protection for an endemic amphibian, and availability of drinkable
      water in the future. A monetary variable consisting of an increase in the rate
      for entry to the area was also incorporated to estimate willingness to pay (WTP)
      for additional protection for the selected attributes. Three hundred four Chilean
      visitors to the reserve were randomly selected for interviews. Econometric
      analysis based on the Theory of Utility Maximization shows that visitors are
      willing to pay to protect the selected attributes. WTP values for the attributes
      range from CHP $2,600 ($5.4) to $6,600 ($14) per person per visit. The results of
      this research provide reserve managers information about tradeoffs that could be
      used to enhance public support and maximise the social benefits of nature
      conservation management programmes.

PMID- 22367363
TI  - The expressions and clinical significances of tissue and serum galectin-3 in
      pancreatic carcinoma.
AB  - PURPOSE: Galectin-3, a member of the beta-galactoside-binding protein family, is
      involved in many biological processes, including cell proliferation, regulating
      cell cycle, angiogenesis, tumorigenesis, metastasis, etc. The aim of this study
      is to elucidate the relationship between galectin-3 and clinicopathological
      variables and to evaluate the clinical significance of serum galectin-3 in the
      diagnosis of pancreas carcinoma. METHODS: Galectin-3 expression in 78 pairs of
      pancreatic carcinoma tissues and the adjacent nontumorous tissues was tested by
      immunohistochemistry. The relationship between galectin-3 expression and clinical
      variables was analyzed. A sensitive method of time-resolved fluorescence
      immunological assay (TRFIA) for the detection of galectin-3 was established, and
      serum galectin-3 in cases with different pancreatic diseases was measured by
      TRFIA and ELISA. Further we compared the sensitivity and specificity of
      determining galectin-3, carcinoembryonic antigen (CEA) and carbohydrate
      antigen199 (CA199) for diagnosis of pancreatic carcinoma and assessed the
      complementary diagnostic value of galectin-3, CEA and CA199 for pancreatic
      carcinoma. RESULTS: Immunohistochemistry showed that galectin-3 expression was
      significantly higher in the human pancreatic carcinoma tissues than in the
      adjacent nontumorous tissues. The expression levels were correlated with the
      differentiation degree with the higher expression in poor differentiation
      tissues. Serum galectin-3 detected by both TRFIA and ELISA was much higher in
      patients with pancreatic carcinoma than in other groups. Serum galectin-3 was not
      correlated with CEA and CA199. Combined determination of these three markers has
      the complementary diagnostic value for human pancreatic carcinoma and may
      increase the diagnostic sensitivity to 97.5%. CONCLUSIONS: Galectin-3 is
      overexpressed in pancreatic carcinoma tissues, and it is correlated with the
      tumor differentiation. Serum galectin-3 is higher in cases with pancreatic
      carcinoma than in benign pancreatic diseases and healthy persons. Combined
      determination of serum galectin-3, CEA and CA199 may improve the diagnostic power
      for pancreatic carcinoma.

PMID- 22367366
TI  - Spatial-temporal dynamics of NDVI and Chl-a concentration from 1998 to 2009 in
      the East coastal zone of China: integrating terrestrial and oceanic components.
AB  - Annual normalized difference vegetation index (NDVI) and chlorophyll-a (Chl-a)
      concentration are the most important large-scale indicators of terrestrial and
      oceanic ecosystem net primary productivity. In this paper, the Sea-viewing Wide
      Field-of-view Sensor level 3 standard mapped image annual products from 1998 to
      2009 are used to study the spatial-temporal characters of terrestrial NDVI and
      oceanic Chl-a concentration on two sides of the coastline of China by using the
      methods of mean value (M), coefficient of variation (CV), the slope of unary
      linear regression model (Slope), and the Hurst index (H). In detail, we
      researched and analyzed the spatial-temporal dynamics, the longitudinal zonality
      and latitudinal zonality, the direction, intensity, and persistency of historical
      changes. The results showed that: (1) spatial patterns of M and CV between NDVI
      and Chl-a concentration from 1998 to 2009 were very different. The dynamic
      variation of terrestrial NDVI was much mild, while the variation of oceanic Chl-a
      concentration was relatively much larger; (2) distinct longitudinal zonality was
      found for Chl-a concentration and NDVI due to their hypersensitivity to the
      distance to shoreline, and strong latitudinal zonality existed for Chl-a
      concentration while terrestrial NDVI had a very weak latitudinal zonality; (3)
      overall, the NDVI showed a slight decreasing trend while the Chl-a concentration
      showed a significant increasing trend in the past 12 years, and both of them
      exhibit strong self-similarity and long-range dependence which indicates opposite
      future trends between land and ocean.

PMID- 22367367
TI  - Effect of dust load on the leaf attributes of the tree species growing along the
      roadside.
AB  - Dust is considered as one of the most widespread air pollutants. The objective of
      the study was to analyse the effect of dust load (DL) on the leaf attributes of
      the four tree species planted along the roadside at a low pollution Banaras Hindu
      University (BHU) campus and a highly polluted industrial area (Chunar, Mirzapur)
      of India. The studied leaf attributes were: leaf area, specific leaf area (SLA),
      relative water content (RWC), leaf nitrogen content (LNC), leaf phosphorus
      content (LPC), chlorophyll content (Chl), maximum stomatal conductance (Gs(max)),
      maximum photosynthetic rate (A (max)) and intrinsic water-use efficiency (WUEi).
      Results showed significant effect of sites and species for DL and the leaf
      attributes. Average DL across the four tree species was greater at Chunar,
      whereas, the average values of leaf attributes were greater at the BHU campus.
      Maximum DL was observed for Tectona grandis at Chunar site and minimum for
      Syzygium cumini at BHU campus. Across the two sites, maximum value of SLA, Chl
      and Gs(max) were exhibited by S. cumini, whereas, the greatest value of RWC, LNC,
      LPC, A (max) and WUEi were observed in Anthocephalus cadamba. A. cadamba and S.
      cumini exhibited 28 and 27 times more dust accumulation, respectively, at the
      most polluted Chunar site as compared to the BHU campus. They also exhibited less
      reduction in A (max) due to dust deposition as compared to the other two species.
      Therefore, both these species may be promoted for plantation along the roadside
      of the sites having greater dust deposition.

PMID- 22367368
TI  - Nerve-sparing class III-IV radical hysterectomy: urodynamic study and surgical
      technique.
AB  - OBJECTIVE: The aim of this study was to demonstrate the impact of the nerve
      sparing radical hysterectomy on the bladder function. METHODS: Patients with
      cervical cancer stage 1B1 to IIB, who underwent type 3 to 4 nerve-sparing radical
      hysterectomy, were evaluated with urodynamic test before and within 6 months from
      surgery. Stage IB2 to IIB patients were treated with platinum-based neoadjuvant
      chemotherapy. Bladder catheter was removed in postoperative day 4, and patients
      were educated to clean intermittent self-catheterization. Urinary symptoms were
      evaluated with a questionnaire administered before and 3, 6, and 12 months after
      surgery. Patients treated with adjuvant chemoradiotherapy were excluded from the
      study. RESULTS: Fifteen patients (stage IB1, 7; IB2, 3; and IIB, 5) completed the
      study. Eight (53%) patients were treated with neoadjuvant chemotherapy. Bilateral
      nerve sparing was feasible in 13 (87%) patients, unilateral in 2 (13%). At
      postoperative day 10, only 3 (20%) patients continued intermittent self
      catheterization. Before surgery, 1 (6.2%) patient had urodynamic symptoms of
      incontinence, and 3 (20%) had overactive bladder detrusor. Postoperative
      urodynamic study (median, 4 months; range, 3-6) showed reduced detrusor activity
      in 8 (53%), overactive detrusor in 4 (27%), and normal profile in 3 (20%)
      patients. Reduced bladder sensation was observed in 2 (12.5%), and residual urine
      more than 30% of bladder capacity in 2 (12.5%) patients, respectively. No patient
      showed de novo incontinence. Bladder compliance was unchanged. CONCLUSIONS: The
      separation of the hypogastric nerve from the parametrium is a feasible surgical
      step, which can be implemented in the radical hysterectomy technique in different
      clinical settings. The comparative urodynamic study showed a mild functional
      impairment in the early postoperative period. The most frequent finding was the
      reduced detrusor activity observed during the voiding phase, consistent with the
      straining needed to void reported in the questionnaire. These data suggest that a
      mild bladder impairment occurs despite the conservation of the hypogastric nerve.

PMID- 22367369
TI  - Different levels of sialyl-Tn antigen expressed on MUC16 in patients with
      endometriosis and ovarian cancer.
AB  - OBJECTIVE: Although CA125 antigen is a useful marker for ovarian cancer, its
      expression is also elevated in endometriosis. The purpose of this study was to
      develop an assay method for evaluating differentially glycosylated MUC16 (CA125
      core protein) in patients with endometriosis and ovarian cancer. MATERIALS AND
      METHODS: We prepared MUC16-enriched fractions from peritoneal fluid of patients
      with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel
      filtration, and evaluated the expression of sialyl-Le, Tn, and sialyl-Tn antigens
      by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed
      to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The
      level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and
      ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic
      criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian
      cancer tissues was observed immunohistochemically. RESULTS: Sialyl-Tn antigen was
      markedly detectable in the MUC16-enriched fractions from conditioned medium of
      ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of
      the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich
      enzyme-linked immunosorbent assay was significantly higher in the patients with
      ovarian cancer than that in the patients with endometriosis (P < 0.001). An
      elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian
      cancer but not all the patients with endometriosis. This level increased more
      prominently in the patients with ovarian cancer than that of MUC16 as both the
      clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was
      frequently found in the patients with serous and endometrioid carcinomas.
      Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and
      endometrioid ovarian cancer tissues. CONCLUSIONS: Estimation of the sTn/MUC16
      level may be useful for discriminating endometriosis from ovarian cancer and for
      evaluating the clinical stage, cytological grade, and histological type of
      ovarian cancer.

PMID- 22367370
TI  - Cervical cancer awareness and screening in Botswana.
AB  - OBJECTIVE: Cervical cancer remains a leading cause of death in many developing
      countries because limited screening by Papanicolaou (Pap) smear. We sought to
      better understand women's beliefs about cervical cancer and screening in
      Botswana, a middle-income African country with high rates of cervical cancer.
      METHODS: We interviewed 289 women attending general medicine or human
      immunodeficiency virus (HIV) clinics, where Pap testing was available, in
      Gaborone, Botswana, in January 2009. RESULTS: About three fourths (72%) of the
      respondents reported having ever had a Pap smear; HIV-positive women were more
      likely to have had a Pap smear than HIV-negative women (80% vs 64%; odds ratio,
      1.97; 95% confidence interval, 1.10-3.55). Screening was also more common among
      women who were older, had higher incomes, or had heard of cervical cancer. Almost
      all participants reported a desire to have a Pap smear. Reasons included to
      determine cervical health (56%), to improve overall health (33%), and to obtain
      early treatment (34%). About half (54%) of the respondents said they did not know
      what causes cervical cancer, and almost none attributed the disease to human
      papillomavirus infection. CONCLUSIONS: Study findings can inform interventions
      that seek to increase cervical cancer awareness and uptake of screening as it
      becomes more widely available.

PMID- 22367371
TI  - Impact of single-nucleotide polymorphisms at the TP53-binding and responsive
      promoter region of BCL2 gene in modulating the phenotypic variability of LGMD2C
      patients.
AB  - Apoptosis of skeletal muscle fibers is a well-known event occurring in patients
      suffering from muscular dystrophies. In this study, we hypothesized that
      functional polymorphisms in genes involved in the mitochondrial apoptotic pathway
      might modulate the apoptotic capacity underlying the muscle loss and contributing
      to intrafamilial and interfamilial variable phenotypes in LGMD2C (Limb Girdle
      Muscular Dystrophy type 2C) patients sharing the same c.521delT mutation in SGCG
      gene. Detection of apoptosis was confirmed on muscle biopsies taken from LGMD2C
      patients using the TUNEL method. We genotyped then ten potentially functional
      SNPs in TP53, BCL-2 and BAX genes involved in the mitochondrial apoptotic
      pathway. Potential genotype-dependent Bcl-2 and p53 protein expressed in skeletal
      muscle was investigated using western blot and ELISA assays. The result showed
      that muscle cells carrying the TP53-R72R and TP53-16 bp del/del genotypes
      displayed an increased p53 level which could be more effective in inducing
      apoptosis by activation of the pro-apoptotic gene expression. In addition, the
      BCL2-938 AA genotype was associated with increased Bcl-2 protein expression in
      muscle from LGMD2C patients compared to -938CC genotype, while there was no
      evidence of significant difference in the BAX haplotype. Our findings suggest
      that increased Bcl-2 protein expression may counteract pro-apoptotic pathways and
      thus reduce the muscle loss. To the best of our knowledge, this is a pioneer
      study evaluating the role of apoptotic BCL-2 and TP53 genes in contributing to
      the phenotypic manifestation of c.521delT mutation in LGMD2C patients. Larger
      studies are needed to validate these findings.

PMID- 22367372
TI  - Micro RNA responses to chronic or acute exposures to low dose ionizing radiation.
AB  - Human health risks of exposure to low dose ionizing radiation remain ambiguous
      and are the subject of intense debate. A wide variety of biological effects are
      induced after cellular exposure to ionizing radiation, but the underlying
      molecular mechanism(s) remain to be completely understood. We hypothesized that
      low dose gamma-radiation-induced effects are controlled by the modulation of
      micro RNA (miRNA) that participate in the control of gene expression at the
      posttranscriptional level and are involved in many cellular processes. We
      monitored the expression of several miRNA in human cells exposed to acute or
      chronic low doses of 10 cGy or a moderate dose of 400 cGy of (137)Cs gamma-rays.
      Dose, dose rate and time dependent differences in the relative expression of
      several miRNA were investigated. The expression patterns of many miRNA differed
      after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e,
      a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were
      upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute
      10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose
      treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to
      be downregulated. These findings provide evidence that low dose and dose rate
      gamma-irradiation dictate the modulation of miRNA, which can result in a
      differential cellular response than occurs at high doses. This information will
      contribute to understanding the risks to human health after exposure to low dose
      radiation.

PMID- 22367373
TI  - UDP-glucuronosyltransferase 1A4 (UGT1A4) polymorphisms in a Jordanian population.
AB  - Glucuronidation is one of the most important phase II metabolic pathways. It is
      catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). One of the
      subfamilies is UGT1A. Allele frequencies in UGT1A4 differ among ethnic groups.
      The aim of this study was to determine the allelic frequency of two most common
      defective alleles: UGT1A4*2 and UGT1A4*3 in a Jordanian population. A total of
      216 healthy Jordanian Volunteers (165 males and 51 females) were included in this
      study. Genotyping for UGT1A4*1, UGT1A4*2 and UGT1A4*3 was done using a well
      established polymerase chain reaction-restriction fragment length polymorphism
      test. Among 216 random individuals studied for UGT1A4*2 mutation there were 26
      individuals who were heterozygous, giving a prevalence of 12% and an allele
      frequency of 6.5%. Only one individual was homozygous for UGT1A4*2. The UGT1A4*3
      mutation was detected as heterozygous in 9 of 216 individuals indicating a
      prevalence of 4.2% and allele frequency of 3.5%. Three individuals were
      homozygous for the UGT1A4*3 indicating a prevalence of 1.4%. The prevalence of
      UGT1A4*2 is similar to the Caucasians but different from other populations whilst
      the UGT1A4*3 prevalence in the Jordanian population is distinct from other
      populations. Our results provide useful information for the Jordanian population
      and for future genotyping of Arab populations in general.

PMID- 22367375
TI  - Epidemiologic and genetic characteristics of alopecia areata (part 1).
AB  - Alopecia areata (AA) is a common, chronic, inflammatory disease resulting in an
      unpredictable, non-scarring form of hair loss. It affects almost 0.1% of the
      general population. Although the cause of AA is poorly understood, it is
      hypothesized to have an autoimmune etiology. Supporting this theory is the fact
      that activated CD4 and CD8 T lymphocytes have been found in characteristic
      perifollicular and intrafollicular inflammatory infiltrates of affected
      individuals' anagen hair follicles. AA provides an excellent opportunity to study
      the role of immunogenetics. In fact, various genes that have a role in regulating
      immunity have also been associated with susceptibility to AA. Several reports
      have indicated a significant association between AA and certain human leukocyte
      antigens (HLA) genes such as HLA-DRB1*0401 and DQB1*. This review provides an
      overview of current knowledge about the molecular genetics of AA. The literature
      review has shown overlapping gene patterns suggestive of common pathogenic
      mechanisms. However, many questions remain unanswered because data about local
      gene expression patterns in affected tissues are still scarce.

PMID- 22367374
TI  - Treatment of localized psoriasis with a topical formulation of zinc pyrithione.
AB  - BACKGROUND: Psoriasis is a common chronic condition of the skin that is resistant
      to many therapies. AIM: To test the efficacy of a topical formulation of zinc
      pyrithione in an emollient base compared with an emollient alone in the treatment
      of psoriasis. METHODS: This was a randomized double-blind clinical trial.
      Patients with localized psoriasis involving less than 10% of body skin areas were
      enrolled in the study. They were randomly allocated to one of two treatment
      groups. Group A was treated with emollient cream containing 0.25% zinc pyrithione
      and group B was treated with emollient cream alone twice daily for 3 months.
      Response to treatment was assessed using PASI scores. RESULTS: Of 60
      participants, 30 patients in group A and 30 patients in group B completed the
      study. The mean PASI scores before and after treatment were 3.4+/-1.8 and 0.9+/
      1.3 in group A (p<0.01), and 4.3+/-2 and 3.9+/-1.3 in group B (p>0.05), and there
      was a significant difference between the two groups' mean PASI scores at the end
      of the study (p<0.01). The differences in the mean PASI scores before and after
      treatment were 2.4+/-2 and 0.4+/-0.1 in groups A and B, respectively (p<0.01).
      CONCLUSION: A topical formulation of zinc pyrithione can be used to treat
      localized psoriasis.

PMID- 22367376
TI  - An ulcerated lesion due to HSV-2 infection with a CD56+ cell predominant
      inflammatory infiltrate.
AB  - CD56+ rich inflammatory infiltrates have been described in several cutaneous
      inflammatory conditions. However, CD56+ cells rarely account for more than 10% of
      the cells in such infiltrates. In certain conditions, such as insect bites or
      infection with herpes virus, CD56+ cells can be up to 43% of the cells in the
      infiltrate. This contrasts with what is observed in natural killer (NK)-cell
      lymphomas, which show a diffuse, atypical infiltrate in which most of the cells
      are CD56+. In this report, we describe a lymphocytic infiltrate in an ulcerated
      lesion on the lip of a 53-year-old man resulting from infection with herpes
      simplex virus type 2. CD56+ cells represented 80 to 90% of the infiltrate,
      showing atypical morphologic features, and clusters of CD56 positive cells were
      also observed.

PMID- 22367377
TI  - A rare variant of generalized granuloma annulare presenting with chronic Epstein
      Barr virus infection: coincidence or association?
AB  - We report a rare variant of generalized granuloma annulare (GGA) in a 62-year-old
      male patient. The patient presented with large, annular, violaceous patches on
      the upper arms and thighs. Histological findings were consistent with
      interstitial granuloma annulare. In addition, high titers of Epstein-Barr Viral
      Capsid Antigen (EBV VCA) and EBV Nuclear Antigen (EBVNA) antibodies were found.
      In-situ hybridization did not reveal EBV RNA in the skin lesions. Immune
      dysregulation in the setting of chronic EBV infection has been suggested as a
      contributing factor to the development of this rare variant of GGA.

PMID- 22367378
TI  - Localized Darier's disease.

PMID- 22367379
TI  - Acitretin-induced pyogenic granuloma.

PMID- 22367380
TI  - Parallel development and course of pheochromocytoma and giant squamous cell
      carcinoma of the leg: a new paraneoplastic syndrome?
AB  - Paraneoplastic syndromes (PS) are diseases or symptom complexes associated with
      malignancy, usually of internal origin, but not directly related to mass effects,
      invasion, or metastatic spread. Rarely, cutaneous squamous cell carcinoma (SCC)
      may be associated with PS. We present a patient with a giant SCC located on the
      right leg and a pheochromocytoma. Considering the concurrent onset and parallel
      course of both pheochromocytoma and SCC in this patient, and the complete
      resolution of the endocrine abnormalities after resection of the skin tumor, it
      was possible to conceive of the pheochromocytoma as a paraneoplastic phenomenon.
      To our knowledge, this association has not been previously described.

PMID- 22367381
TI  - Ulceration of the scalp: lipogranuloma induced by industrial oils in an interior
      decorator.

PMID- 22367383
TI  - Anti-aging effects of high molecular weight proteoglycan from salmon nasal
      cartilage in hairless mice.
AB  - Proteoglycans comprise a family of complex macromolecules consisting of a core
      protein with covalently attached glycosaminoglycan (GAG) chains. The skin anti
      aging effects of oral administration of proteoglycan fractions with different
      molecular weights from salmon nasal cartilage were investigated in a hairless
      mouse model of skin aging; aging was caused by repeated ultraviolet B (UVB)
      irradiation. Three proteoglycan fractions of different molecular weights were
      prepared from salmon nasal cartilage water extract by ion-exchange column
      chromatography and gel filtration column chromatography. Physiological and
      histological analysis of the skin indicated that oral administration of high
      molecular weight proteoglycan inhibited UVB-induced skin aging, defined as
      increased erythema, increased transepidermal water loss (TEWL), decreased
      hydration, and epidermal and dermal hypertrophies. The serum and dorsal skin
      inflammatory cytokine levels indicated that high molecular weight proteoglycan
      acts on gut immunity and improves skin by inhibiting surplus inflammatory
      cytokines produced by UVB irradiation. These results suggest that high molecular
      weight proteoglycan from salmon nasal cartilage is effective in preventing skin
      aging.

PMID- 22367382
TI  - Patterns of striatal degeneration in frontotemporal dementia.
AB  - Behavioral variant frontotemporal dementia and semantic dementia have been
      associated with striatal degeneration, but few studies have delineated striatal
      subregion volumes in vivo or related them to the clinical phenotype. We traced
      caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify
      volumes of these structures in behavioral variant frontotemporal dementia,
      semantic dementia, Alzheimer disease, and healthy controls (n=12 per group). We
      further related these striatal volumes to clinical deficits and neuropathologic
      findings in a subset of patients. Behavioral variant frontotemporal dementia and
      semantic dementia showed significant overall striatal atrophy compared with
      controls. Moreover, behavioral variant frontotemporal dementia showed panstriatal
      degeneration, whereas semantic dementia featured a more focal pattern involving
      putamen and accumbens. Right-sided striatal atrophy, especially in the putamen,
      correlated with the overall behavioral symptom severity and with specific
      behavioral domains. At autopsy, patients with behavioral variant frontotemporal
      dementia and semantic dementia showed striking and severe tau or TAR DNA-binding
      protein of 43 kDa pathology, especially in ventral parts of the striatum. These
      results demonstrate that ventral striatum degeneration is a prominent shared
      feature in behavioral variant frontotemporal dementia and semantic dementia and
      may contribute to the social-emotional deficits common to both disorders.

PMID- 22367384
TI  - Procalcitonin is more useful than C-reactive protein in differentiation of fever
      in patients with sickle cell disease.
AB  - This study aimed at evaluating the value of C-reactive protein (CRP) and
      procalcitonin (PCT) levels in the differential diagnosis of fever in patients
      with sickle cell disease (SCD). The study included 86 children with SCD (group 1)
      and 49 controls (group 2). During the study, the patients had 114 acute episodes
      or routine visits to the units. They were classified as having vasoocclusive
      crisis with fever (group 1A), vasoocclusive crisis without fever (group 1B), and
      no crisis or fever (steady state, group 1C). Only patients with crises were
      admitted to the hospital. Patients admitted to the hospital with various clinical
      signs and symptoms each and every time were included in groups 1A, 1B, and 1C.
      Thus, a total of 114 clinical episodes were analyzed. The mean CRP levels in the
      3 patient groups were significantly higher than that in the group 2, and among
      the patient groups, the mean CRP was significantly higher in group 1A than the
      other groups. The mean CRP level in group 1A and group 1B was significantly
      higher than that in group 1C. There were no significant differences among the 3
      SCD groups in terms of the median serum PCT level; however, the median PCT level
      in group 1A, group 1B, and group 1C patients was significantly higher than that
      in group 2 patients. These data indicate that vasoocclusive disease with or
      without fever apparently does not significantly increase PCT levels in relation
      to the baseline status of children with SCD, which in turn are clearly more
      elevated than PCT levels of control children.

PMID- 22367385
TI  - The outcome of allogeneic hematopoietic stem cell transplants without total body
      irradiation in pediatric patients with acute lymphoblastic leukemia:  single
      centre experience.
AB  - The most widely accepted conditioning regimen to allogeneic hematopoietic stem
      cell transplantation consists of total body irradiation, especially in patients
      affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we
      report our experience on hematopoietic stem cell transplantation in 44 pediatric
      patients with acute lymphoblastic leukemia using a non-radiation-based
      conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation
      was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in
      complete remission. At a median follow-up of 390 days, the probabilities of 3
      year disease-free survival and overall survival were 50% and 68%, respectively.
      Disease status of hematopoietic stem cell transplantation was the only
      significant variable affecting the overall survival. Acute and chronic graft
      versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively.
      Relapse was significantly higher among patients transplanted in advanced disease
      status. The results of the study indicate that non-radiation-based preparative
      regimens can be used in pediatric patients with ALL. However, well-designed
      comparative trials are needed to better clarify the difference between radiation
      and non-radiation-based conditioning regimens in pediatric ALL.

PMID- 22367386
TI  - The diagnostic value of interleukin-6 and interleukin-8 for early prediction of
      bacteremia and sepsis in children with febrile neutropenia and cancer.
AB  - BACKGROUND AND AIM: Early diagnosis of sepsis in children with febrile
      neutropenia and cancer still remains a challenge for modern medicine because of
      lack of specific laboratory markers and clinical signs especially at the
      beginning of the infection. The objective of this study was to evaluate the
      ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis
      during the first 2 days in oncohematologic patients with febrile neutropenia.
      PATIENTS AND METHODS: A total of 61 febrile neutropenic episodes in 37 children
      were studied. Serum samples were collected on day 1 and day 2 from the onset of
      fever and analyzed using an automated random access analyzer. RESULTS:
      Neutropenic children with febrile episodes were classified into the following 2
      groups: (1) fever of unknown origin group--patients with a negative blood culture
      -and (2) bacteremia/sepsis group--patients with a positive blood culture or
      clinical sepsis. High negative predictive values were found on day 1 for
      interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of
      bacteremia/sepsis. CONCLUSIONS: These interleukins could be used as a screening
      tool for the rejection of sepsis or bacteremia on the first day of fever in
      neutropenic children with cancer.

PMID- 22367387
TI  - Cyto-morphologic evaluation of bone marrow in infants with disseminated
      neuroblastoma.
AB  - We studied the prevalence and degree of tumor cell infiltration (TCI) in bone
      marrow (BM) aspirates of 89 infants with stage 4/4 S neuroblastoma and correlated
      them with MYCN gene status and patient outcome. TCI was scored 0, +, ++, and +++,
      the last corresponding to an infiltration greater than 10%. TCI 0 was more
      frequent in stage 4 than in stage 4 S. TCI + and ++ were equally represented. TCI
      +++ was found only in 9 patients, all with typical stage 4 features (bone or lung
      involvement). Overall survival was not significantly influenced by the presence
      and degree of TCI.

PMID- 22367388
TI  - Solitary retrovesical lesion in a newborn.

PMID- 22367390
TI  - Renal cell carcinoma presented with hypocalcemia in an adolescent.
AB  - Renal cell carcinoma is very rare in childhood. It is a different entity from its
      adult counterpart. We report a case of renal cell carcinoma presented with
      hypocalcemia in a 16-year-old girl that is, to the best of our knowledge, the
      first such published incident. The patient was treated by radical nephrectomy
      with regional lymphadenectomy. Hypocalcemia amended after surgery. Neither
      chemotherapy nor radiotherapy was given. She has remained disease free for 34
      months.

PMID- 22367391
TI  - First case report of a peripheral T-cell lymphoma, not otherwise specified, of
      the central nervous system in a child.
AB  - We report on the first pediatric patient with a localized primary peripheral T
      cell lymphoma, not otherwise specified, of the central nervous system (CNS). The
      solid lesion that was enhanced in magnetic resonance images of the left
      precentral region was totally resected. The histopathology revealed a peripheral
      T-cell lymphoma, not otherwise specified. Staging procedures showed that the
      lesion was confined to the CNS. Without any further therapy, the patient still
      remains in complete remission 6 years after diagnosis. Thus, we conclude that a
      peripheral T-cell lymphoma, not otherwise specified, of the CNS can occur in
      children. In the case presented here, complete resection sufficed.

PMID- 22367392
TI  - Protease signalling: the cutting edge.
AB  - Protease research has undergone a major expansion in the last decade, largely due
      to the extremely rapid development of new technologies, such as quantitative
      proteomics and in-vivo imaging, as well as an extensive use of in-vivo models.
      These have led to identification of physiological substrates and resulted in a
      paradigm shift from the concept of proteases as protein-degrading enzymes to
      proteases as key signalling molecules. However, we are still at the beginning of
      an understanding of protease signalling pathways. We have only identified a minor
      subset of true physiological substrates for a limited number of proteases, and
      their physiological regulation is still not well understood. Similarly, links
      with other signalling systems are not well established. Herein, we will highlight
      current challenges in protease research.

PMID- 22367393
TI  - Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and
      organismal growth in Drosophila.
AB  - The nutrient/target-of-rapamycin (TOR) pathway has emerged as a key regulator of
      tissue and organismal growth in metazoans. The signalling components of the
      nutrient/TOR pathway are well defined; however, the downstream effectors are less
      understood. Here, we show that the control of RNA polymerase (Pol) III-dependent
      transcription is an essential target of TOR in Drosophila. We find that TOR
      activity controls Pol III in growing larvae via inhibition of the repressor Maf1
      and, in part, via the transcription factor Drosophila Myc (dMyc). Moreover, we
      show that loss of the Pol III factor, Brf, leads to reduced tissue and organismal
      growth and prevents TOR-induced cellular growth. TOR activity in the larval fat
      body, a tissue equivalent to vertebrate fat or liver, couples nutrition to
      insulin release from the brain. Accordingly, we find that fat-specific loss of
      Brf phenocopies nutrient limitation and TOR inhibition, leading to decreased
      systemic insulin signalling and reduced organismal growth. Thus, stimulation of
      Pol III is a key downstream effector of TOR in the control of cellular and
      systemic growth.

PMID- 22367394
TI  - Evaluation of low-level laser therapy in patients with acute and chronic
      temporomandibular disorders.
AB  - The purpose of this study was to address the following question: among patients
      with acute or chronic temporomandibular disorders (TMD), does low-level laser
      therapy (LLLT) reduce pain intensity and improve maximal mouth opening? The
      sample comprised myogenic TMD patients (according Research Diagnostic Criteria
      for TMD). Inclusion criteria were: male/female, no age limit, orofacial pain,
      tender points, limited jaw movements and chewing difficulties. Patients with
      other TMD subtypes or associated musculoskeletal/rheumatologic disease, missing
      incisors teeth, LLLT contra-indication, and previous TMD treatment were excluded.
      According to disease duration, patients were allocated into two groups, acute (<6
      months) and chronic TMD (>= 6 months). For each patient, 12 LLLT sessions were
      performed (gallium-aluminum-arsenide; lambda = 830 nm, P = 40 mW, CW, ED = 8
      J/cm(2)). Pain intensity was recorded using a 10-cm visual analog scale and
      maximal mouth opening using a digital ruler (both recorded before/after LLLT).
      The investigators were previously calibrated and blinded to the groups (double
      blind study) and level of significance was 5% (p < 0.05). Fifty-eight patients
      met all criteria, 32 (acute TMD), and 26 (chronic TMD). Both groups had a
      significant pain intensity reduction and maximal mouth opening improvement after
      LLLT (Wilcoxon test, p < 0.001). Between the groups, acute TMD patient had a more
      significant pain intensity reduction (Mann-Whitney test, p = 0.002) and a more
      significant maximal mouth opening improvement (Mann-Whitney test, p = 0.011). Low
      level laser therapy can be considered as an alternative physical modality or
      supplementary approach for management of acute and chronic myogenic
      temporomandibular disorder; however, patients with acute disease are likely to
      have a better outcome.

PMID- 22367395
TI  - Board certification in psychology: insights from medicine and hospital
      psychology.
AB  - For physicians board certification is an accepted tradition that research
      suggests improves services and outcomes. In contrast, relatively few
      psychologists pursue board certification suggesting ambivalence or limited
      contingencies reinforcing it. The authors report on medical school and hospital
      based psychologists' attitudes toward board certification and current
      certification status. About one-fifth (21.7%) of the sample were certified by the
      American Board of Professional Psychology, a greater proportion than
      psychologists generally: Highest rates were seen in neuropsychology (7.5%),
      clinical psychology (6.4%), clinical child and adolescent psychology (3.2%) and
      clinical health psychology (2.8%). Few (<2%) reported their hospitals required
      board certification. Half recognized benefits to the profession for psychologists
      pursuing board certification, yet 70% opposed requiring it for their hospital
      based practice. Forces seeking to promote healthcare quality ultimately may
      increase expectations for board certification. If consumers, employers, hospitals
      and managed care organizations demand board certification for health
      professionals, greater numbers of psychologists would likely seek it.

PMID- 22367396
TI  - Activation of PI3K/Akt and ERK signaling pathways antagonized sinomenine-induced
      lung cancer cell apoptosis.
AB  - Sinomenine (SIN) is a bioactive component derived from a Chinese medicinal plant.
      Our previous studies demonstrated that SIN has cytotoxic effects on human lung
      cancer cells. However, the antitumor molecular mechanisms of SIN have yet to be
      elucidated in detail. In the present study, we further explored the effects of
      SIN on NCI-H460 human lung cancer cell viability and apoptosis and investigated
      the regulation and function of PI3K/Akt and ERK signaling pathways during SIN
      induced apoptosis in various lung cancer cell lines. NCI-H460 cells were
      incubated with 200 ug/ml SIN for the indicated times (0, 24, 48 or 72 h). Cell
      viability was assessed by MTT assay. Akt, p-Akt, ERK1/2 and p-ERK1/2 protein
      levels were detected by western blotting, respectively. Two different selective
      inhibitors (LY294002 for the PI3K pathway; PD98059 for the MEK/ERK pathway) were
      used to characterize the relative roles of PI3K/Akt and ERK in SIN-induced
      apoptosis. Apoptosis was determined by flow cytometry. SIN inhibited the
      proliferation of NCI-H460 cells in a time-dependent manner, which was accompanied
      with significant activation of pAkt and pERK. LY294002 and PD98059 both
      significantly increased SIN-induced apoptosis in NCI-H460, NCI-H226 and NCI-H522
      cells. Our findings suggest that the activation of the PI3K/Akt and ERK signaling
      pathways antagonize SIN-induced lung cancer cell apoptosis and molecules that
      inhibit these pathways should potentiate the effects of SIN. This study
      represents a significant step forward in our understanding of the signal
      transduction pathways associated with the apoptosis elicited by SIN.

PMID- 22367397
TI  - HIV-associated sensory neuropathy: risk factors and genetics.
AB  - HIV-associated sensory neuropathy (HIV-SN) remains a common neurological
      complication of HIV infection despite the introduction of effective
      antiretroviral therapies. Exposure to neurotoxic antiretroviral drugs and
      increasing age have consistently been identified as risk factors for HIV-SN,
      while comorbid conditions with underlying predisposition to cause peripheral
      neuropathy (eg, diabetes mellitus, malnutrition, isoniazid exposure), ethnicity,
      and increasing height also have been implicated. Genetic association studies have
      identified genes affecting mitochondrial function and genes involved in the
      inflammatory response that modify the risk for HIV-SN among patients exposed to
      neurotoxic antiretrovirals. However, there is a lack of data on clinical,
      demographic, and genetic risk factors for HIV-SN in the modern era, with the rate
      of HIV-SN remaining unacceptably high despite the introduction of safer
      medications. Thus, more work is required to identify the principal factors that
      increase an individual's risk for HIV-SN so that effective preventative or
      therapeutic strategies can be implemented.

PMID- 22367398
TI  - Unilateral hemispherectomy at adulthood asymmetrically affects motor performance
      of male Swiss mice.
AB  - Evidence exists indicating that cerebral lateralization is a fundamental feature
      of all vertebrates. In humans, a series of studies demonstrated that the left
      hemisphere plays a major role in controlling movement. No such asymmetries have
      been identified in rodents, in spite of the fact that these animals have been
      frequently used in studies assessing motor behavior. In this regard, here, we
      used unilateral hemispherectomy to study the relative importance of each
      hemisphere in controlling movement. Adult Swiss mice were submitted to right
      unilateral hemispherectomy (RH), left unilateral hemispherectomy (LH) or sham
      surgery. Fifteen days after surgery, motor performance was assessed in the
      accelerating rotarod test and in the foot-fault test (in which performance
      depends on skilled limb use) and in the elevated body swing test (in which
      performance depends on trunk movements). The surgical removal of the right
      hemisphere caused a more pronounced impairment in performance than the removal of
      the left hemisphere both in the rotarod and in the foot-fault tests. In the
      rotarod, the RH group presented smaller latencies to fall than both LH and sham
      groups. In the foot-fault test, while both the sham and the LH groups showed no
      differences between left and right hind limbs, the RH group showed significantly
      worse performance with the left hind limb than with the right one. The elevated
      body swing test revealed a similar impairment in the two hemispherectomized
      groups. Our data suggest a major role of the right hemisphere in controlling
      skilled limb movements in mice.

PMID- 22367399
TI  - Audiovisual time perception is spatially specific.
AB  - Our sensory systems face a daily barrage of auditory and visual signals whose
      arrival times form a wide range of audiovisual asynchronies. These temporal
      relationships constitute an important metric for the nervous system when
      surmising which signals originate from common external events. Internal
      consistency is known to be aided by sensory adaptation: repeated exposure to
      consistent asynchrony brings perceived arrival times closer to simultaneity.
      However, given the diverse nature of our audiovisual environment, functionally
      useful adaptation would need to be constrained to signals that were generated
      together. In the current study, we investigate the role of two potential
      constraining factors: spatial and contextual correspondence. By employing an
      experimental design that allows independent control of both factors, we show that
      observers are able to simultaneously adapt to two opposing temporal
      relationships, provided they are segregated in space. No such recalibration was
      observed when spatial segregation was replaced by contextual stimulus features
      (in this case, pitch and spatial frequency). These effects provide support for
      dedicated asynchrony mechanisms that interact with spatially selective mechanisms
      early in visual and auditory sensory pathways.

PMID- 22367400
TI  - Systematic changes in the perceived posture of the wrist and elbow during
      formation of a phantom hand and arm.
AB  - Our previous study showed that a fully flexed or extended hand became perceived
      as an extended or flexed 'phantom' hand as ischemic anesthesia progressed (Inui
      et al. in J Physiol 589:5775-5784, 2011). Here, we examined what happened if the
      hand was held in the midposition before and during the anesthesia. Twenty healthy
      participants reported the perceived postures of their right wrist and elbow
      during an ischemic block of the right upper arm using the left hand and arm. If
      the actual arm and hand were fully extended, then the perceived position of the
      elbow and wrist moved toward flexion. Conversely, if they were fully flexed, then
      the perceived position of the joints moved toward extension. However, when the
      hand was held in the midposition before and during the anesthesia, the position
      of the wrist was perceived to be in the same position. Hence, the fully flexed or
      extended position of a limb was essential for systematic changes in the perceived
      posture of the limb during the anesthesia. Because the start of these changes
      occurred as somatosensory inputs were declining, the changes depended on the
      fading inputs from strongly stretched muscle and skin during the anesthesia.

PMID- 22367401
TI  - Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures.
AB  - The synthesis, physico-chemical properties and biological effects of a new class
      of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and
      alkylate it through an electrophilic quinone methide moiety (QM), are reported.
      FRET and circular dichroism assays showed a marked stabilization and selectivity
      towards telomeric G4 DNA folded in a hybrid topology. NDI-QMs' alkylating
      properties revealed a good reactivity on single nucleosides and selectivity
      towards telomeric G4. A selected NDI was able to significantly impair the growth
      of melanoma cells by causing telomere dysfunction and down-regulation of
      telomerase expression. These findings points to our hybrid ligand-alkylating NDIs
      as possible tools for the development of novel targeted anticancer therapies.

PMID- 22367402
TI  - Periodontal disease, Porphyromonas gingivalis serum antibody levels and
      orodigestive cancer mortality.
AB  - Periodontitis, the progressive loss of the alveolar bone around the teeth and the
      major cause of tooth loss in adults, is due to oral microorganisms, including
      Porphyromonas gingivalis. Periodontitis is associated with a local overly
      aggressive immune response and a spectrum of systemic effects, but the role of
      this condition in orodigestive cancers is unclear. We prospectively examined
      clinically ascertained periodontitis (N = 12,605) and serum IgG immune response
      to P.gingivalis (N = 7852) in relation to orodigestive cancer mortality among men
      and women in the National Health and Nutrition Examination Survey III. A detailed
      oral health exam was conducted from 1988 to 1994 in survey Phases I and II,
      whereas serum IgG for P.gingivalis was measured from 1991 to 1994 in Phase II
      only. One hundred and five orodigestive cancer deaths were ascertained through 31
      December 2006. Periodontitis (moderate or severe) was associated with increased
      orodigestive cancer mortality [relative risks (RR) = 2.28, 95% confidence
      interval (CI) = 1.17-4.45]; mortality risks also increased with increasing
      severity of periodontal disease (P trend = 0.01). Periodontitis-associated
      mortality was in excess for colorectal (RR = 3.58; 95% CI = 1.15-11.16) and
      possibly for pancreatic cancer (RR = 4.56; 95% CI = 0.93-22.29). Greater serum
      P.gingivalis IgG tended to be associated overall with increased orodigestive
      cancer mortality (P trend = 0.06); P.gingivalis-associated excess orodigestive
      mortality was also found for healthy subjects not exhibiting overt periodontal
      disease (RR = 2.25; 95% CI = 1.23-4.14). Orodigestive cancer mortality is related
      to periodontitis and to the periodontal pathogen, P.gingivalis, independent of
      periodontal disease. Porphyromonas gingivalis is a biomarker for microbe
      associated risk of death due to orodigestive cancer.

PMID- 22367403
TI  - Screening of antimicrobials from Caribbean sea animals and isolation of
      bactericidal proteins from the littoral mollusk Cenchritis muricatus.
AB  - Marine organisms represent approximately half of the world's biodiversity by
      virtue of the sea being an immense reservoir of bioactive molecules. Here,
      antimicrobial crude extract activities of different marine invertebrates from the
      Caribbean Sea were evaluated. One of the most active, crude extracts was that
      marine snail Cenchritis muricatus, it was capable of totally inhibiting the
      development of Staphylococcus aureus and also showed a growth inhibition of 95.9%
      in Escherichia coli. Aiming to isolate molecules that confirm antimicrobial
      activity, the crude extract was purified by reversed-phase HPLC C-18
      chromatography. Thereafter, one of the obtained fractions preserved this
      antibacterial activity. Furthermore, SDS-PAGE analysis (15%) showed the presence
      of two proteins of molecular masses with approximately 10 and 15 kDa,
      respectively. The first 19 amino acids of both proteins were sequenced by using
      Edman degradation, yielding unidentified primary structures compared against
      sequences deposited at NCBI databank. This is the first report of antibacterial
      proteins isolated from the mollusk Cenchritis muricatus and these proteins could
      be used as antibiotic alternatives in the aquacultural industry, as well as in
      agricultural or biomedical research.

PMID- 22367404
TI  - The fairness of the Epworth Sleepiness Scale: two approaches to differential item
      functioning.
AB  - PURPOSE: Differential item functioning (DIF) is said to exist in an item if a
      subject's response to the item is affected by other aspects than that which the
      test is intended to assess. DIF might affect the validity of a test. The aim of
      this study was thus to examine whether any of the items in the Epworth Sleepiness
      Scale (ESS) exhibits DIF regarding age or gender, and if so, to which degree.
      METHODS: Using previously collected cross-sectional ESS data from 1,168 subjects
      with different clinical characteristics (61% males, mean age 67.8 year (SD 12.2
      year)), ordinal regression as well as Rasch-based DIF analyses were performed.
      RESULTS: Concerning age, both DIF analyses showed DIF for age in items 3
      (inactive in a public place), 4 (passenger in a car), and 8 (in a car that has
      stopped in traffic). The Rasch model also showed DIF for gender in item 3. The
      DIF magnitudes as judged by McFadden pseudo-R (2) changes were, however, only
      minor. CONCLUSIONS: ESS has small but reproducible DIF for age in items 3, 4, and
      8. The detected DIF might be worth to consider in large-sample studies, although
      it probably has no effect on an individual basis.

PMID- 22367405
TI  - Genetic variant in TP63 on locus 3q28 is associated with risk of lung
      adenocarcinoma among never-smoking females in Asia.
AB  - A recent genome-wide association study (GWAS) of subjects from Japan and South
      Korea reported a novel association between the TP63 locus on chromosome 3q28 and
      risk of lung adenocarcinoma (p = 7.3 * 10(-12)); however, this association did
      not achieve genome-wide significance (p <= 10(-7)) among never-smoking males or
      females. To determine if this association with lung cancer risk is independent of
      tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405
      and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never
      smoking female controls from 10 studies conducted in Taiwan, Mainland China,
      South Korea, and Singapore. Genetic variation in rs10937405 was associated with
      risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 * 10(-8); allelic risk =
      0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of
      association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037;
      allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence
      that genetic variation in TP63 is associated with the risk of lung adenocarcinoma
      among Asian females in the absence of tobacco smoking.

PMID- 22367407
TI  - Analysis of airborne pollen fall in Nicosia (Cyprus).
AB  - Airborne pollen distribution in the city of Nicosia (Cyprus) was measured
      volumetrically during two consecutive years 2007-2008 on weekly basis using
      Lanzoni trap (Lanzoni VPPS 2000). A total of 7,880 pollen grains/m(3) belonging
      to 44 taxa, in 2007 were 3,593 pollen grains/m(3) and in 2008 it was 4,287 pollen
      grains/m(3), were determined. Out of these, 25 belonged to the arboreal and 19 to
      the non-arboreal taxa. At the end of 2 years, total pollen counts were 78.76%
      arboreal, 19.32% non-arboreal, and 1.92% unidentified taxa. The number of pollen
      in the arboreal plants followed the trend as Pinaceae (29.96%),
      Cupressaceae/Taxaceae (18.33%), Olea europaea L. (6.92%), and Quercus spp.
      (4.92%), and for non-arboreal representatives, these were Poaceae (8.46%),
      Chenopodiaceae/Amaranthaceae (2.61%), Plantago spp. (1.69%), and Parietaria spp.
      (1.51%). The distribution of pollen in the atmosphere of Nicosia followed the
      trend as March, April, May, and June.

PMID- 22367406
TI  - Evolutionary genetics of the human Rh blood group system.
AB  - The evolutionary history of variation in the human Rh blood group system,
      determined by variants in the RHD and RHCE genes, has long been an unresolved
      puzzle in human genetics. Prior to medical treatments and interventions developed
      in the last century, the D-positive (RhD positive) children of D-negative (RhD
      negative) women were at risk for hemolytic disease of the newborn, if the mother
      produced anti-D antibodies following sensitization to the blood of a previous D
      positive child. Given the deleterious fitness consequences of this disease, the
      appreciable frequencies in European populations of the responsible RHD gene
      deletion variant (for example, 0.43 in our study) seem surprising. In this study,
      we used new molecular and genomic data generated from four HapMap population
      samples to test the idea that positive selection for an as-of-yet unknown fitness
      benefit of the RHD deletion may have offset the otherwise negative fitness
      effects of hemolytic disease of the newborn. We found no evidence that positive
      natural selection affected the frequency of the RHD deletion. Thus, the initial
      rise to intermediate frequency of the RHD deletion in European populations may
      simply be explained by genetic drift/founder effect, or by an older or more
      complex sweep that we are insufficiently powered to detect. However, our
      simulations recapitulate previous findings that selection on the RHD deletion is
      frequency dependent and weak or absent near 0.5. Therefore, once such a frequency
      was achieved, it could have been maintained by a relatively small amount of
      genetic drift. We unexpectedly observed evidence for positive selection on the C
      allele of RHCE in non-African populations (on chromosomes with intact copies of
      the RHD gene) in the form of an unusually high F( ST ) value and the high
      frequency of a single haplotype carrying the C allele. RhCE function is not well
      understood, but the C/c antigenic variant is clinically relevant and can result
      in hemolytic disease of the newborn, albeit much less commonly and severely than
      that related to the D-negative blood type. Therefore, the potential fitness
      benefits of the RHCE C allele are currently unknown but merit further
      exploration.

PMID- 22367408
TI  - The long-term surgical outcomes of secondary hemidystonia associated with post
      traumatic brain injury.
AB  - BACKGROUND: The aim was to assess the effect of deep brain stimulation for
      secondary hemidystonias associated with focal post-traumatic brain injuries.
      METHODS: Four patients underwent deep brain stimulation for the treatment of
      medically refractory secondary hemidystonia associated with post-traumatic brain
      injury. Clinical outcome assessments were based on Burke-Fahn-Marsden Dystonia
      Rating Scale movement and disability scores. Health-related quality of life was
      assessed using a 36-item short-form general health survey questionnaire
      administered preoperatively and at the last follow-up visit. RESULTS: Burke-Fahn
      Marsden Dystonia Rating Scale movement scores had improved by 73.2% (range, 38.1
      94.1) and disability scores had improved by 75% (range, 60-100) at the 2-year
      follow-up visit. The health-related quality of life assessment revealed
      satisfactory results at follow-up, such that body pain, general health, vitality,
      social functioning, as well as emotional and mental health improved
      significantly. CONCLUSIONS: Globus pallidus internus deep brain stimulation can
      be used to modulate and ameliorate secondary hemidystonia associated with focal
      post-traumatic brain injury.

PMID- 22367409
TI  - Tophaceous pseudogout of the thoracic spine.
AB  - Calcium pyrophosphate dihydrate deposition disease (CPDD, tophaceous pseudogout)
      is a rare crystal arthropathy characterized by pyrophosphate crystal deposition
      in joints, synovitis and chondrocalcinosis on imaging. We present the case of a
      72-year-old man with 6 months of left chest pain; magnetic resonance imaging
      revealed a T9/T10 herniated disc. Intraoperatively, the material was sent for
      pathological analysis revealing pseudogout. Axial calcium pyrophosphate crystal
      deposition is rare but reported in the literature and found at the craniocervical
      junction and skull. Spinal calcium pyrophosphate crystal deposition is rare in
      the thoracic spine. It is often asymptompatic and can involve the disc or
      ligaments. This case demonstrates a unique presentation of CPDD.

PMID- 22367410
TI  - Dose-escalated simultaneous integrated-boost treatment of prostate cancer
      patients via helical tomotherapy.
AB  - PURPOSE: The goal of this work was to assess the feasibility of moderately
      hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy
      (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer
      regarding acute side effects and dose-volume histogram data (DVH data). METHODS:
      Acute side effects and DVH data were evaluated of the first 40 intermediate risk
      prostate cancer patients treated with a definitive daily image-guided SIB-IMRT
      protocol via helical tomotherapy in our department. The planning target volume
      including the prostate and the base of the seminal vesicles with safety margins
      was treated with 70 Gy in 35 fractions. The boost volume containing the prostate
      and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of
      76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall
      were set in order not to exceed the dose of 76 Gy prescribed to the boost volume.
      Acute toxicity was evaluated prospectively using a modified CTCAE (Common
      Terminology Criteria for Adverse Events) score. RESULTS: SIB-IMRT allowed good
      rectal sparing, although the full boost dose was permitted to the anterior rectal
      wall. Median rectum dose was 38 Gy in all patients and the median volumes
      receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and
      3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was
      observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and
      urological side effects occurred in 25% and 57.5%, respectively. No correlation
      was found between acute toxicity and the DVH data. CONCLUSION: This institutional
      SIB-IMRT protocol using daily image guidance as a precondition for smaller safety
      margins allows dose escalation to the prostate without increasing acute toxicity.

PMID- 22367411
TI  - Methodological issues in designing and reporting health-related quality of life
      in cancer clinical trials: the challenge of brain cancer studies.
AB  - Health-related quality of life (HRQOL) and other types of patient-reported
      outcomes (PROs) are now important outcome measures in cancer clinical trials. A
      number of potentially less toxic drugs are available, and newer treatments can
      potentially offer cancer patients the possibility to be treated with less
      aggressive approaches, making PROs more critical in evaluating treatment
      effectiveness. However, assessing PROs in clinical trials requires careful
      consideration of a number of methodological issues. Robust methodology and
      accurate reporting of results are crucial to provide the scientific community and
      health care providers with a transparent message about the impact of a given drug
      or a new medical approach on patients' health status. This paper provides basic
      guidance on methodological issues to be addressed when designing and reporting
      HRQOL in clinical trials and presents examples of relevant brain cancer studies.

PMID- 22367412
TI  - Pilocytic astrocytoma survival in adults: analysis of the Surveillance,
      Epidemiology, and End Results Program of the National Cancer Institute.
AB  - Pilocytic astrocytoma is a WHO grade 1 brain tumor common in children. Relatively
      little is known about the behavior of pilocytic astrocytomas in adult patients,
      largely due to the rarity of pilocytic astrocytoma in this population. Some data
      suggest that adults share the excellent prognosis seen in children, while other
      reports suggest more aggressive tumor behavior in adult patients. Patients
      diagnosed with pilocytic astrocytoma between 1973 and 2008 were identified in the
      National Cancer Institute Surveillance, Epidemiology, and End Results Program
      database. Age-group specific survival was analyzed with overall, expected, and
      cancer-specific survival rates. Further survival analyses were performed with the
      Kaplan-Meier method and Cox Proportional Hazards models. 3,066 patients with
      pilocytic astrocytoma were identified, including 865 patients aged 20 years and
      older. Survival rates declined significantly with age, from 96.5% 60-month
      survival in patients 5-19 years (95% CI 95.3-97.4) to 52.9% 60-month survival in
      adult patients 60+ years of age (95% CI 38.4-65.5), with a corresponding decrease
      in relative and cancer-specific survival rates. Gross total resection was a
      positive prognostic indicator in adults, while patients receiving radiation had
      shorter survival regardless of extent of resection. Pilocytic astrocytoma is
      associated with higher mortality in adult patients than in children and teens,
      and survival decreases with increasing age in adults. The morbidity of pilocytic
      astrocytoma in adults provides rationale for future trials of adjuvant treatment
      in high-risk patients.

PMID- 22367413
TI  - A multi-drug delivery system with sequential release using titania nanotube
      arrays.
AB  - A multi-drug delivery system with sequential release based on titania nanotube
      arrays and polymer micelles as drug carriers is presented. Delivery of multiple
      water insoluble and soluble drugs required for combined local therapy is
      demonstrated.

PMID- 22367414
TI  - Primary Ewing sarcoma of lumbar spine in an 8-year-old boy:  a case report.
AB  - Primary Ewing's sarcoma of the mobile spine is rare, but nevertheless, is the
      second most common primary malignant bone neoplasm in children. Furthermore, in
      contrast to long bone involvement, delays may occur because symptoms may not be
      present until neurological deficits occur. Here, we report a case of an 8-year
      old boy with lower back pain and radicular pain on the posterior lower
      extremities with tingling and progressively reduced sensation in both feet. The
      patient initially seemed to have muscle sprain but was eventually diagnosed with
      Ewing's sarcoma of the L5 vertebra with intraspinal extension.

PMID- 22367416
TI  - A training programme to improve hip strength in persons with lower limb
      amputation.
AB  - OBJECTIVE: To investigate the effect of a 10-week training programme on persons
      with a lower limb amputation and to determine if this training is sufficient to
      enable running. SUBJECTS: Seven transtibial, 8 transfemoral and 1 bilateral
      amputee (all resulting from trauma, tumour or congenital) were randomly assigned
      to a training (n  =8) or control group (n = 8). METHODS: Isokinetic hip flexor
      and extensor strength at 60 and 120o/s and oxygen consumption while walking at 
      1.0 m/s were tested pre- and post- a 10-week period. The training group followed
      a twice weekly hip strengthening programme, while the control group continued
      with  their usual activities. Running ability was determined pre-testing, and
      attempted after post-testing for the training group only. RESULTS: The training
      group increased hip strength and decreased oxygen consumption. Six amputees who
      were previously unable to run were able to after training. The control group
      decreased intact limb hip extensor strength. CONCLUSION: The training programme
      is sufficient to improve hip strength and enable running in persons with a lower
      limb amputation. As hip strength was reduced in those not following the training
      programme, it is recommended that strength training be undertaken regularly in
      order to avoid losing limb strength following amputation.

PMID- 22367417
TI  - Combination of citalopram plus paliperidone is better than citalopram alone in
      the treatment of somatoform disorder:  results of a 6-week randomized study.
AB  - The objective of this study was to evaluate the effectiveness and tolerability of
      citalopram versus citalopram plus paliperidone combination therapy in patients
      with somatoform disorders (SDs). In this 6-week, randomized, fixed-dose study, 60
      patients with SD (ICD-10 F45.0), undifferentiated SD (F45.1), and somatoform
      autonomic dysfunction (F45.3) were randomly assigned to receive citalopram (20
      mg/day) with or without paliperidone (3 mg/day). Four scales were used to
      evaluate effectiveness and tolerability at baseline and at the end of the second,
      fourth, and sixth week after treatment: Somatoform Disorders Screening Symptoms-7
      (SOMS-7), Hamilton Anxiety Scale (HAMA), 17-item Hamilton Depression Scale (HAMD
      17), and Treatment Emergent Symptom Scale (TESS). The rater was blinded to the
      kind of treatment patients received. (i) In the intention-to-treat population (N
      = 51), the overall response ratio (50% reduction in SMOS-7 scores) was
      significantly higher in the citalopram-paliperidone group compared with the
      citalopram group after a 6-week treatment (71.4 vs. 38.10%, chi2 = 4.71, P =
      0.03). (ii) The SOMS-7 and somatic subscore of the Hamilton Anxiety Scale (HAMA
      SOM) total score of the citalopram plus paliperidone group decreased more
      significantly than that of the citalopram group, and a significant difference
      could be observed at the end of 4 weeks of treatment. (iii) There was no
      significant difference between the two groups in adverse effects, and no serious
      adverse event was reported in both groups. Our findings indicate that a
      combination with paliperidone is significantly better than monotherapy with
      citalopram whether synergistic or add-on for patients with SDs. Our results call
      for future studies with larger sample sizes and a longer duration to draw more
      definitive conclusions.

PMID- 22367415
TI  - Gene expression profiles of spleen, liver, and head kidney in turbot
      (Scophthalmus maximus) along the infection process with Philasterides
      dicentrarchi using an immune-enriched oligo-microarray.
AB  - We evaluated the expression profiles of turbot in spleen, liver, and head kidney
      across five temporal points of the Philasterides dicentrarchi infection process
      using an 8x15K Agilent oligo-microarray. The microarray included 2,176 different
      fivefold replicated gene probes designed from a turbot 3' sequenced EST database.
      We were able to identify 221 differentially expressed (DE) genes (8.1% of the
      whole microarray), 113 in spleen, 83 in liver, and 90 in head kidney, in at least
      1 of the 5 temporal points sampled for each organ. Most of these genes could be
      annotated (83.0%) and functionally categorized using GO terms (69.1%) after the
      additional sequencing of DE genes from the 5' end. Many DE genes were related to
      innate and acquired immune functions. A high proportion of DE genes were organ
      specific (70.6%), although their associated GO functions showed notable
      similarities in the three organs. The most striking difference in functional
      distribution was observed between the up- and downregulated gene groups.
      Upregulated genes were mostly associated to immune functions, while downregulated
      ones mainly involved metabolism-related genes. Genetic response appeared
      clustered in a few groups of genes with similar expression profiles along the
      temporal series. The information obtained will aid to understand the turbot
      immune response and will specifically be valuable to develop strategies of
      defense to P. dicentrarchi to achieve more resistant broodstocks for turbot
      industry.

PMID- 22367418
TI  - A mathematical view on the decoupled sites representation.
AB  - The decoupled sites representation (DSR) is a theoretical instrument which allows
      to regard complex pH titration curves of biomolecules with several interacting
      proton binding sites as composition of isolated, non-interacting sites, each with
      a standard Henderson-Hasselbalch titration curve. In this work, we present the
      mathematical framework in which the DSR is embedded and give mathematical proofs
      for several statements in the periphery of the DSR. These proofs also identify
      exceptions. To apply the DSR to any molecule, it is necessary to extend the set
      of binding energies from R to a stripe within C. An important observation in this
      context is that even positive interaction energies (repulsion) between the
      binding sites will not guarantee real binding energies in the decoupled system,
      at least if the molecule has more than four proton binding sites. Moreover, we
      show that for a given overall titration curve it is not only possible to find a
      corresponding system with an interaction energy of zero but with any arbitrary
      fix interaction energy. This result also effects practical work as it shows that
      for any given titration curve, there is an infinite number of corresponding
      hypothetical molecules. Furthermore, this implies that--using a common definition
      of cooperative binding on the level of interaction energies--a meaningful measure
      of cooperativity between the binding sites cannot be defined solely on the basis
      of the overall titration. Consequently, all measures of cooperativity based on
      the overall binding curve do not measure the type of cooperativity commonly
      defined on the basis of interaction energies. Understanding the DSR
      mathematically provides the basis of transferring the DSR to biomolecules with
      different types of interacting ligands, such as protons and electrons, which play
      an important role within electron transport chains like in photosynthesis.

PMID- 22367419
TI  - Assessing gender identity concerns in children and adolescents: evaluation,
      treatments, and outcomes.
AB  - Child and adolescent psychiatrists are increasingly evaluating youth who present
      with gender-nonconforming behaviors and identities. The lack of discipline
      specific guidelines has made assessment and treatment of children and adolescents
      presenting with these concerns more difficult. Several new guidelines have
      recently been published, and research efforts are advancing to broaden the scope
      of understanding of gender identity assessment and treatment in children and
      adolescents. Familiarity with the latest standards of care, recent research
      advances, and current knowledge gaps is important to help improve clinical
      competency in treating mental health issues in this population.

PMID- 22367420
TI  - Immunotherapy for SV40 T/t antigen-induced breast cancer by recombinant adeno
      associated virus serotype 2 carrying interleukin-15 in mice.
AB  - Human interleukin-15 (hIL15) exerts anticancer effects through the activities of
      lymphokine-activated killer (LAK) cells. However, its short half-life hinders its
      clinical application. Recombinant adeno-associated virus serotype 2 (rAAV2) is
      used for hIL15 gene transfer vectors, because of its low immunogenicity and long
      term gene expression in human clinical trials. SV40 T/t antigens are related with
      many human epithelial cancers and are generally found in human breast cancer. In
      order to demonstrate the anticancer effects of hIL15 on SV40 T/t antigen-induced
      breast cancer, rAAV2-hIL15 was constructed and an SV40 T/t antigen-induced
      transgenic mouse breast cancer model was established. Our study showed that rAAV2
      hIL15 could express the hIL15 protein with anticancer bioactivity. In addition,
      rAAV2-hIL15 could activate the cytotoxic activity of LAK cells in vivo.
      Furthermore, the rAAV2-hIL15 successfully delayed cancer growth and eventually
      led to cancer cell death in SV40 T/t antigen-induced breast cancer transgenic
      mice. In summary, our study indicates that rAAV2-hIL15 may be applied for cancer
      immunotherapy of SV40 T/t antigen-induced breast cancer.

PMID- 22367423
TI  - Encephalitis caused by flaviviruses.
AB  - The genus Flavivirus, family Flaviviridae, contains some of the most important
      arboviral pathogens of man. The genus includes several aetiological agents of
      encephalitis, the most significant being Japanese encephalitis virus, West Nile
      virus and tick-borne encephalitis virus. In each case, the majority of exposed
      individuals will not develop disease, but a minority will develop a severe
      illness with a significant chance of permanent neurological damage or death. The
      factors that determine this are numerous, involving complex interactions between
      virus and host and are still being actively uncovered. In many cases it appears
      that the immune response, while crucial to containing the virus and limiting
      spread to the brain, is also responsible for causing neurological damage. Innate
      responses can limit viral replication but may also be responsible for generating
      pathological levels of inflammation. Neutralizing antibody responses are
      protective but take time to develop. The role of T cells is less clear, and may
      be either protective or pathogenic. This review summarizes recent developments in
      the understanding of the pathogenesis of encephalitis caused by flaviviruses.

PMID- 22367424
TI  - Oviposition induced volatile emissions from African smallholder farmers' maize
      varieties.
AB  - Maize (corn), Zea mays, is a genetically diverse crop, and we have recently shown
      that certain open pollinated varieties (OPVs) of Latin American origin possess a
      trait not present in mainstream commercial varieties: they produce volatiles in
      response to stemborer oviposition that are attractive to stemborer parasitoids.
      Here, we tested whether a similar tritrophic effect occurs in the African OPVs
      'Nyamula' and 'Jowi'. Herbivore induced plant volatiles (HIPVs) were collected
      from plants exposed to egg deposition by the stemborer Chilo partellus. In a four
      arm olfactometer bioassay, the parasitic wasp Cotesia sesamiae preferred samples
      containing HIPVs from plants with eggs to samples collected from plants without
      eggs. EAG-active compounds, including (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT),
      were released in higher amounts from the egg induced headspace samples. Our
      results suggest that this oviposition trait is not limited to S. American Z. mays
      germplasm, and that it could be used to increase indirect defense against attack
      by stemborers.

PMID- 22367425
TI  - Pachyman treatment improves CD4+CD25+ Treg counts and serum interleukin 4 and
      interferon gamma levels in a mouse model of Kawasaki disease.
AB  - The aim of this study was to explore the effect of pachyman, a mushroom extract,
      on CD4+CD25+ regulatory T cells (Tregs), serum interleukin 4 (IL-4) and
      interferon gamma (IFN-gamma) levels in a mouse model of Kawasaki disease.
      Lactobacillus casei cell wall extract was diluted to 1 mg/ml in PBS and
      administered to mice by intraperitoneal injection to establish a model of
      Kawasaki disease. Sixty female mice were used in this study, 40 of which were
      randomly assigned to a model (normal saline by gavage, n=20) or experimental
      group (200 mg/kg/day pachyman by gavage, n=20). The remaining 20 mice were
      disease and treatment-free, and were used as the control group. Compared to the
      control mice, mice in the model group exhibited a significantly lower percentage
      of CD4+CD25+ Tregs and significantly higher serum IL-4 and IFN-gamma levels
      (P<0.05). However, CD4+CD25+ Tregs significantly increased and IL-4 and IFN-gamma
      levels significantly decreased in experimental mice following pachyman treatment
      (P<0.05). Further analysis showed a negative correlation between CD4+CD25+ Tregs
      and IL-4/IFN-gamma levels (P<0.05). In conclusion, pachyman improves immune
      function in a mouse model of Kawasaki disease by upregulating CD4+CD25+ Tregs,
      which may inhibit the cytokine secretion of Th1 and Th2 cells.

PMID- 22367426
TI  - Effect of age and gender on pharmacokinetics and pharmacodynamics of a single
      ticagrelor dose in healthy individuals.
AB  - PURPOSE: The aim of this study was to assess age and gender effects on ticagrelor
      pharmacokinetics and pharmacodynamics (PK/PD). METHODS: Forty healthy individuals
      [18-45 years (young); >= 65 years (elderly); ten men, ten women per age group)
      received 200 mg ticagrelor. RESULTS: Ticagrelor was rapidly absorbed [time to
      maximum concentration (C(max)) (t(max)) 2.5-3.0 h], and its major active
      metabolite, AR-C124910XX rapidly formed (t(max) 3.0-3.5 h) in all groups.
      Ticagrelor exposure was higher in elderly vs. the young [area under the curve
      from time 0 to infinity (AUC(0-infinity)) 52%; C(max) 63% higher] and women vs.
      men (AUC(0-infinity) 37%; C(max) 52% higher). Mean terminal elimination half-life
      was slightly longer in women vs. men but was unaffected by age. Similar results
      were observed for AR-C124910XX (elderly vs. young, AUC(0-infinity) 48%; C(max)
      61% higher), and in women vs. men (AUC(0-infinity) 55%; C(max) 56% higher).
      Across all groups, ticagrelor produced substantial final-extent inhibition of
      platelet aggregation (IPA): >90% at 4 and 8 h postdose. Individuals with highest
      ticagrelor exposure (i.e., elderly) had the lowest IPA, indicating an age-related
      platelet sensitivity effect. In young individuals, platelet sensitivity was
      greater in men vs. women. Ticagrelor tolerability was not affected by age or
      gender. CONCLUSIONS: Systemic exposures to ticagrelor and AR-C124910XX were
      higher in elderly vs. young and in women vs. men. Age- and gender-related changes
      in IPA were apparent, but substantial IPA was achieved in all groups. No
      adjustment in ticagrelor dose should be considered necessary based on age and
      gender.

PMID- 22367427
TI  - N-3 fatty acid supplementation to routine statin treatment inhibits platelet
      function, decreases patients' daytime blood pressure, and improves inflammatory
      status.
AB  - OBJECTIVES: N-3 fatty acids reduce the risks of cardiovascular morbidity and
      mortality. Administration of N-3 fatty acids to patients treated with statins may
      potentiate the treatment effects. We examined the operating mechanisms underlying
      such a combination. METHODS: Thirty-two hypercholesterolemic patients aged 30-70
      years with hypercholesterolemia controlled by statins, received sequential
      treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks.
      Scheduled clinical visits included physical examination, 24-h blood pressure
      measurement, endothelial function evaluated by pulse wave analysis, analyses for
      platelet function, inflammation markers [interleukin (IL)-6, plasminogen
      activator inhibitor-1 (PAI-1)] and oxidative stress parameters (STAT-8
      Isoprostane) were undertaken at baseline, after placebo treatment, and after 6
      and 20 weeks of N-3 fatty acid intake. RESULTS: Platelets functions were
      significantly inhibited, whereas endothelial function parameters were unaltered.
      IL-6 significantly decreased whereas PAI-1and STAT-8-Isoprostane levels remained
      unaffected. Daytime blood pressure significantly decreased; however, nighttime
      pressure and heart rate remained unchanged. No evidence of lipid-profile
      improvement was observed following combined treatment with statins and N-3 fatty
      acids. CONCLUSIONS: In hypercholesterolemic patients, combination of statins and
      N-3 fatty acid inhibits platelet aggregation, alters inflammatory status, and
      positively affects daytime blood pressure. Close long-term follow-up might reveal
      additional beneficial effects of N-3 fatty acids in this patient population.

PMID- 22367428
TI  - Buccal and intranasal lorazepam clinical pharmacokinetics: can it adequately
      compete with intravenous lorazepam in pediatric care patients?

PMID- 22367429
TI  - Chemoenzymatic formal synthesis of (-)- and (+)-epibatidine.
AB  - The cis-dihydrocatechol, derived from enzymatic cis-dihydroxylation of
      bromobenzene using the microorganism Pseudomonas putida UV4, was converted into (
      )-epibatidine in eleven steps with complete stereocontrol. In addition, an
      unprecedented palladium-catalysed disproportionation reaction gave the (+)
      enantiomer of an advanced key intermediate employed in a previous synthesis of
      epibatidine.

PMID- 22367430
TI  - Drug-induced sleep endoscopy (DISE) for non-CPAP treatment selection in patients
      with sleep-disordered breathing.

PMID- 22367432
TI  - An examination of healthy aging across a conceptual continuum: prevalence
      estimates, demographic patterns, and validity.
AB  - BACKGROUND: Although the notion of healthy aging has gained wide acceptance in
      gerontology, measuring the phenomenon is challenging. Guided by a prominent
      conceptualization of healthy aging, we examined how shifting from a more to less
      stringent definition of healthy aging influences prevalence estimates,
      demographic patterns, and validity. METHODS: Data are from adults aged 65 years
      and older who participated in the Health and Retirement Study. We examined four
      operational definitions of healthy aging. For each, we calculated prevalence
      estimates and examined the odds of healthy aging by age, education, gender, and
      race-ethnicity in 2006. We also examined the association between healthy aging
      and both self-rated health and death. RESULTS: Across definitions, the prevalence
      of healthy aging ranged from 3.3% to 35.5%. For all definitions, those classified
      as experiencing healthy aging had lower odds of fair or poor self-rated health
      and death over an 8-year period. The odds of being classified as "healthy" were
      lower among those of advanced age, those with less education, and women than for
      their corresponding counterparts across all definitions. CONCLUSIONS: Moving
      across the conceptual continuum--from a more to less rigid definition of healthy
      aging--markedly increases the measured prevalence of healthy aging. Importantly,
      results suggest that all examined definitions identified a subgroup of older
      adults who had substantially lower odds of reporting fair or poor health and
      dying over an 8-year period, providing evidence of the validity of our
      definitions. Conceptualizations that emphasize symptomatic disease and functional
      health may be particularly useful for public health purposes.

PMID- 22367431
TI  - Long-term assessment of inflammation and healthy aging in late life: the
      Cardiovascular Health Study All Stars.
AB  - BACKGROUND: Associations of inflammation with age-related pathologies are
      documented; however, it is not understood how changes in inflammation over time
      impact healthy aging. METHODS: We examined associations of long-term change in C
      reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical
      and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality
      in 1,051 participants in the Cardiovascular Health Study All Stars Study.
      Biomarkers were measured in 1996-1997 and 2005-2006. RESULTS: In 2005-2006,
      median age was 84.9 years, 63% were women and 17% non-white; 21% had at least a
      doubling in CRP over time and 23% had at least a doubling in IL-6. Adjusting for
      demographics, CVD risk factors, and 1996-1997 CRP level, each doubling in CRP
      change over 9 years was associated with higher risk of physical or cognitive
      impairment (odds ratio 1.29; 95% confidence interval 1.15, 1.45). Results were
      similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not
      CRP, was associated with incident CVD events; hazard ratio (95% confidence
      interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was
      individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16,
      1.65]). In models containing both change and 2005-2006 level, only level was
      associated with CVD events and mortality. CONCLUSIONS: Although increases in
      inflammation markers over 9 years were associated with higher concurrent risk of
      functional impairment and subsequent CVD events and mortality, final levels of
      each biomarker appeared to be more important in determining risk of subsequent
      events than change over time.

PMID- 22367434
TI  - Inverse susceptibility to oxidative death of lymphocytes obtained from
      Alzheimer's patients and skin cancer survivors: increased apoptosis in
      Alzheimer's and reduced necrosis in cancer.
AB  - A paucity of cancer in individuals with Alzheimer's disease (AD) and low rates of
      AD in cancer survivors has been reported in epidemiological studies. Deregulation
      in opposite directions of biological mechanisms, such as susceptibility to cell
      death, might be shared in the two disorders. We analyzed lymphocytes from AD and
      skin cancer patients as well as healthy controls and found significantly
      increased vulnerability of AD lymphocytes to H(2)O(2)-induced apoptotic death and
      higher resistance to death of skin cancer lymphocytes, due to reduced necrosis,
      as compared with healthy controls by pairwise comparisons adjusted for age and
      sex. H(2)O(2)-induced death in lymphocytes was caspase independent and
      significantly reduced by PARP-1 inhibition in all three groups. These differences
      in the susceptibility to cell death observed for lymphocytes from AD and skin
      cancer patients may be one of the mechanisms that help explain the inverse
      correlation detected between these diseases in epidemiological studies.

PMID- 22367435
TI  - Getting to the heart of the matter: age-related changes in diastolic heart
      function in the longest-lived rodent, the naked mole rat.
AB  - The naked mole rat is an extremely long-lived (>31 years) small (35 g) rodent.
      Moreover, it maintains good health for most of its long life. We hypothesized
      that naked mole rats also show attenuated cardiac aging. With age, cardiac muscle
      can become less compliant, causing a decline in early diastolic filling (E) and a
      compensatory increase in atrial contraction-induced late filling (A). This
      results in decreased left ventricular E/A ratio. Doppler imaging showed no
      significant differences in E/A ratios (p = .48) among old (18-20 years) breeders
      and nonbreeders despite differences in estrogen levels. A cross-sectional study
      of 1- to 20-year-old naked mole rats (n = 76) revealed that E/A ratios declined
      with age in females (n = 40; p = .002) but not in males (n = 36; p = 0.45).
      Despite this, neither gender shows increased morbidity or mortality with age.
      These findings suggest that, notwithstanding the previously observed high lipid
      peroxidation in heart tissue, NMRs must possess mechanisms to stave off
      progression to fatal cardiac disease.

PMID- 22367436
TI  - Patterns of focal gray matter atrophy are associated with bradykinesia and gait
      disturbances in older adults.
AB  - OBJECTIVES: Identify the neuroimaging correlates of parkinsonian signs in older
      adults living in the community. METHODS: Magnetic resonance imaging was obtained
      in 307 adults (82.9 years, 55% women, 39% blacks) concurrently with the Unified
      Parkinson Disease Rating scale-motor part. Magnetic resonance imaging measures
      included volume of whole-brain white matter hyperintensities and of gray matter
      for primary sensorimotor, supplementary motor, medial temporal areas, cerebellum,
      prefronto-parietal cortex, and basal ganglia. RESULTS: About 25% of the
      participants had bradykinesia, 26% had gait disturbances, and 12% had tremor.
      Compared with those without, adults with any one of these signs were older,
      walked more slowly, had worse scores on tests of cognition, mood and processing
      speed, and higher white matter hyperintensities volume (all p <= .002). Gray
      matter volume of primary sensorimotor area was associated with bradykinesia
      (standardized odds ratio [95% confidence interval]: 0.46 [0.31, 0.68], p <
      .0001), and gray matter volume of medial temporal area was associated with gait
      disturbances (0.56 [0.42, 0.83], p < .0001), independent of white matter
      hyperintensities volume and age. Further adjustment for measures of muscle
      strength, cardiovascular health factors, cognition, processing speed, and mood or
      for gait speed did not substantially change these results. CONCLUSIONS: Atrophy
      within primary sensorimotor and medial temporal areas might be important for
      development of bradykinesia and of gait disturbances in community-dwelling
      elderly adults. The pathways underlying these associations may not include
      changes in white matter hyperintensities volume, cognition, information
      processing speed, mood, or gait speed.

PMID- 22367438
TI  - Genome-wide two-locus epistasis scans in prostate cancer using two European
      populations.
AB  - Approximately 40 single nucleotide polymorphisms (SNPs) that are associated with
      prostate cancer (PCa) risk have been identified through genome-wide association
      studies (GWAS). However, these GWAS-identified PCa risk-associated SNPs can
      explain only a small proportion of heritability (~13%) of PCa risk. Gene-gene
      interaction is speculated to be one of the major factors contributing to the so
      called missing heritability. To evaluate the gene-gene interaction and PCa risk,
      we performed a two-stage genome-wide gene-gene interaction scan using a novel
      statistical approach named "Boolean Operation-based Screening and Testing". In
      the first stage, we exhaustively evaluated all pairs of SNP-SNP interactions for
      ~500,000 SNPs in 1,176 PCa cases and 1,101 control subjects from the National
      Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) study. No SNP
      SNP interaction reached a genome-wide significant level of 4.4E-13. The second
      stage of the study involved evaluation of the top 1,325 pairs of SNP-SNP
      interactions (P(interaction) <1.0E-08) implicated in CGEMS in another GWAS
      population of 1,964 PCa cases from the Johns Hopkins Hospital (JHH) and 3,172
      control subjects from the Illumina iControl database. Sixteen pairs of SNP-SNP
      interactions were significant in the JHH population at a P(interaction) cutoff of
      0.01. However, none of the 16 pairs of SNP-SNP interactions were significant
      after adjusting for multiple tests. The current study represents one of the first
      attempts to explore the high-dimensional etiology of PCa on a genome-wide scale.
      Our results suggested a list of SNP-SNP interactions that can be followed in
      other replication studies.

PMID- 22367437
TI  - The significance of neuronal lateralisation in Parkinson's disease.
AB  - The destruction of the dopaminergic neurons in the substantia nigra (SN) and
      consequent depletion of striatal dopamine elicits the main movement deficits
      related to Parkinson's disease (PD). In the early stages of the illness, the
      motor symptoms are often exhibited asymmetrically. Thus, the onset of PD features
      starts on either the right or left side. The side of onset appears to determine
      the prognosis of the disorder and other features, such as right-side tremor
      dominance has a better prognosis in contrast to left-side dominant bradykinesia
      rigidity. In addition, left-side onset of motor features is associated with
      cognitive decline. Therefore, an intricate relation appears to exist between the
      side of disease onset and progression/severity and other non-motor symptoms.
      Unilateral PD in turn corresponds to neuronal nigrostriatal degeneration in the
      contralateral hemisphere. Indeed positron emission tomography has demonstrated a
      positive correlation between symptom asymmetry and brain function (Hoorn et al.
      Parkinsonism Relat Disord 17:58-60, 2011), which corresponds to a unilateral
      pattern of degeneration. This phenomenon appears to be exclusive to PD.
      Additionally, the variation in motor symptom(s) dominance exhibited in the
      disorder conforms to the notion that PD is a spectrum disease with many sub
      groups. Thus, clinical and post mortem studies on "lateralisation" may serve as a
      vital tool in understanding the mechanism(s) eliciting the characteristic
      destruction of the SN neurons. Additionally, it may be employed as a predictive
      indicator for the symptomology and prognosis of the illness thus allowing
      selective treatment strategies targeted at the pronounced hemispheric
      degeneration.

PMID- 22367440
TI  - Appendectomy by residents is safe and not associated with a higher incidence of
      complications: a retrospective cohort study.
AB  - OBJECTIVE: The purpose of this retrospective cohort study was to investigate
      whether current practice where residents perform appendectomies affects quality
      of care. Therefore, we investigated whether there was a difference in incidence
      of complications and mortality in appendectomies performed by surgeons (S),
      supervised residents (SR), or unsupervised residents (UR). BACKGROUND:
      Appendicitis is among the most frequent conditions requiring urgent surgery.
      Admittance and surgery are often managed by residents. Recent studies have shown
      that laparoscopic appendectomy can be safely performed by residents. It is not
      known whether these results are applicable on appendectomies in general. METHODS:
      All patients undergoing appendectomy in our hospital between January 1, 2000, and
      December 31, 2009, were included in the analysis. Patients undergoing
      appendectomy by surgeons, supervised residents, and unsupervised residents were
      compared. Primary endpoints were complications and mortality. RESULTS: During the
      study period, 1538 patients were operated. The risk of complications (S: 20% vs
      SR: 17% vs UR: 16%; P = 0.209, S vs SR; P = 0.149, S vs UR; and P = 0.872, SR vs
      UR) and mortality (S: 0.3% vs SR: 0.2% vs UR: 0.4%, P = 1.000 for all
      comparisons) were similar in all groups. In the multivariate model, the odds
      ratio for complications in the group operated by supervised residents was 0.84
      (95% CI: 0.58-1.22, P = 0.357) versus 0.81 (95% CI: 0.55-1.18, P = 0.265) in the
      unsupervised residents' group. CONCLUSIONS: Current practice where residents
      perform appendectomies either unsupervised or supervised by an experienced
      surgeon should not be discouraged. We found that it is safe and does not lead to
      more complications or negatively affect quality of care.

PMID- 22367439
TI  - NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy.
AB  - While pathogenic copy number variations (CNVs) in 15q11.2 were recently
      identified in Caucasian patients with idiopathic generalized epilepsies (IGEs),
      the epilepsy-associated gene(s) in this region is/are still unknown. Our study
      investigated whether the CNVs in 15q11.2 are associated with childhood absence
      epilepsy (CAE) in Chinese patients and whether the selective magnesium
      transporter NIPA2 gene affected by 15q11.2 microdeletions is a susceptive gene
      for CAE. We assessed IGE-related CNVs by Affymetrix SNP 5.0 microarrays in 198
      patients with CAE and 198 controls from northern China, and verified the
      identified CNVs by high-density oligonucleotide-based CGH microarrays. The coding
      region and exon-intron boundaries of NIPA2 were sequenced in all 380 patients
      with CAE and 400 controls. 15q11.2 microdeletions were detected in 3 of 198
      (1.5%) patients and in no controls. Furthermore, we identified point mutations or
      indel in a heterozygous state of the NIPA2 gene in 3 out of 380 patients, whereas
      they were absent in 700 controls (P = 0.043). These mutations included two novel
      missense mutations (c.532A>T, p.I178F; c.731A>G, p.N244S) and one small novel
      insertion (c.1002_1003insGAT, p.N334_335EinsD). No NIPA2 mutation was found in
      400 normal controls. We first identified that NIPA2, encoding a selective
      magnesium transporter, is a susceptible gene of CAE, and 15q11.2 microdeletions
      are important pathogenic CNVs for CAE with higher frequency in Chinese
      populations than that previously reported in Caucasians. The haploinsufficiency
      of NIPA2 may be a mechanism underlying the neurological phenotypes of 15q11.2
      microdeletions.

PMID- 22367441
TI  - Surgery in Castleman's disease: a systematic review of 404 published cases.
AB  - OBJECTIVES: We undertook a systematic review of 404 published cases of
      Castleman's disease to identify the role of the surgeon beyond assistance in
      tissue-based diagnosis. BACKGROUND: Castleman's disease is a rare primary disease
      of the lymph node caused by infection with herpesviridae. Little is known about
      the role of surgery in this condition. DATA SOURCES: Medline, Embase, Cochrane
      Database of Systematic Reviews, ISI Thompson Web of Knowledge, and hand search of
      articles' bibliography. STUDY SELECTION: Of the 1791 citations identified through
      the initial electronic search and screened for possible inclusion, 488 articles
      were retained after title and abstract reviews. Of these, 239 were accepted for
      this review. DATA EXTRACTION: A complete dataset containing age, gender,
      centricity (unicentric vs multicentric), histopathologic type (hyaline vascular
      [HV] vs plasma cell [PC]), anatomical location of the only focus in unicentric
      Castleman's disease (UCD) or the dominant focus in multicentric Castleman's
      disease (MCD), nature of the surgical approach (resective vs diagnostic), and
      outcome (disease-free survival [DFS] vs death due to disease) was extracted.
      RESULTS: A resective or debulking surgical approach was described in 77.0% of all
      patients, but was far more common in unicentric (262/278; 94.2%) than
      multicentric (49/126; 38.9%) disease (chi2 146.8; P < 0.0001). Unicentric disease
      had a significantly higher overall survival (95.3% vs 61.1%; chi2 55.7; P <
      0.0001), 3 year DFS (89.7% vs 55.6%; chi2 27.8; P < 0.0001), and 5 year DFS
      (81.2% vs 34.4%; chi2 28.6; P < 0.0001) than multicentric disease. Failure to
      treat unicentric disease by resective surgery resulted in a significant mortality
      (17.6% vs 3.8% chi2; P < 0.05). In multicentric disease, outcomes are comparable
      between debulking surgery alone, immunochemotherapy alone, or a combination of
      both (28.0% vs 28.9% vs 50.0%; P = nonsignificant). CONCLUSIONS: Surgery is the
      gold standard for treatment of unicentric Castelman's disease. The role of
      debulking surgery in human immunodeficiency virus (-) MCD needs to be evaluated
      in prospective studies.

PMID- 22367442
TI  - Association between hospital intraoperative blood transfusion practices for
      surgical blood loss and hospital surgical mortality rates.
AB  - OBJECTIVE: Blood loss during surgery is an important operative complication in
      patients undergoing major noncardiac surgery and may increase postoperative
      morbidity and mortality. Variations in the delivery of operative blood
      transfusions to treat blood loss depend not only on the patient and surgery
      characteristics but also on the hospital transfusion practices, and may explain
      differences in the hospitals' postoperative outcomes. We determine the
      relationship between hospital-level rates of intraoperative blood transfusion and
      30-day mortality among older patients with significant intraoperative blood loss.
      METHODS: Among 46,608 operative patients aged 65 years or older whose estimated
      blood loss was 500 mL or greater in 122 Veterans Affairs (VA) hospitals during
      years 1997 to 2004, we examined the relationship between hospital-level
      transfusion rates and adjusted 30-day postoperative mortality rates using linear
      regression modeling. RESULTS: Hospital-level rates of intraoperative blood
      transfusion for older surgical patients with significant blood loss varied from
      10% to 92%. Hospitals in the highest tertile for the rate of intraoperative
      transfusion had the highest number of patients with 500 mL or more surgical blood
      loss and lowest risk-adjusted 30-day surgical mortality. For every 10% increase
      in the rate of intraoperative blood transfusion, there was a 0.7% (95% CI: 0.3%
      1.1%) decrease in the hospital's adjusted 30-day postoperative mortality for
      these high-risk patients. CONCLUSIONS: Large variation exists in hospitals'
      intraoperative blood transfusion practices for older patients with significant
      surgical blood loss. Hospitals with higher transfusion rates for patients with
      significant surgical blood loss have lower adjusted 30-day mortality for these
      patients. Hospital intraoperative blood transfusion practices may be a promising
      surgical quality indicator.

PMID- 22367443
TI  - Cost-effectiveness of adding FDG-PET or CT to the diagnostic work-up of patients
      with stage III melanoma.
AB  - OBJECTIVE: The aim of this prospective study was to assess predictive value of
      fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography
      (CT) and to analyze their cost-effectiveness in several diagnosis-treatment
      combinations. BACKGROUND: The incidence of melanoma continues to rise. A
      proportion will present or recur with lymph node metastases (American Joint
      Committee on Cancer/Union for International Cancer Control stage III). To detect
      distant metastases, CT and/or FDG-PET are available. However, few studies have
      assessed their value and costs in stage III. METHODS: All consecutive patients
      with melanoma with palpable, proven lymph node metastases (2003-2008) referred
      for examination with FDG-PET and CT were prospectively included. Sensitivity,
      specificity, and accuracy, and positive predictive value (PPV) and negative
      predictive value (NPV) were calculated. In economic evaluation, the costs of
      diagnostic work-up with and without FDG-PET and CT were compared. RESULTS:
      Overall, 253 patients with melanoma were included. FDG-PET showed a higher
      sensitivity than CT: 86.1% compared with 78.2%. Specificity was higher for CT
      (93.7%) compared with FDG-PET (93.1%). Overall, FDG-PET showed a higher PPV and
      NPV. Cost-consequence analysis showed that adding CT (True-Positive upstaging in
      61 patients) to diagnostic work-up decreased cost by 5.5%, adding FDG-PET (True
      Positive upstaging in 68 patients) increased cost by 7.2%, and adding both (True
      Positive upstaging in 78 patients) increased cost by 15.1%. CONCLUSIONS: In this
      study, FDG-PET had higher sensitivity and predictive value, whereas CT had a
      higher specificity. Adding one of these diagnostic tools improved the staging of
      stage III patients with less than 10% cost increase. A proposal for stage
      specific use of imaging modalities for clinicians caring for patients with
      melanoma is presented.

PMID- 22367444
TI  - Clinical significance of left trisectionectomy for perihilar cholangiocarcinoma:
      an appraisal and comparison with left hepatectomy.
AB  - OBJECTIVE: To review our experiences with left-sided hepatectomy for perihilar
      cholangiocarcinoma, to compare left hepatectomy with left trisectionectomy, and
      to evaluate the clinical significance of left trisectionectomy from the viewpoint
      of surgical oncology. BACKGROUND: Only 4 large case series have been reported on
      left trisectionectomy, with only a few patients diagnosed with perihilar
      cholangiocarcinoma. Therefore, the oncologic advantage of left trisectionectomy
      compared with left hepatectomy for perihilar cholangiocarcinoma is still unclear.
      METHODS: This study involved 201 patients who underwent left-sided hepatectomy
      for perihilar cholangiocarcinoma (86 trisectionectomies and 115 hepatectomies).
      Surgical outcome and survival were compared between the 2 types of hepatectomy.
      The length of the resected right posterior bile duct was also measured. RESULTS:
      Patients who underwent trisectionectomy had more advanced tumors, thus requiring
      combined vascular and/or other organ resection. Operative time and blood loss
      were significantly greater in trisectionectomy than in hepatectomy; therefore,
      overall morbidity was significantly higher in the former (59.3% vs 33.0%, P <
      0.001). Mortality was similar (1.2% vs 0.9%) in both techniques. The length of
      the resected supraportal right posterior bile duct was significantly longer in
      trisectionectomy than in hepatectomy (20.7 +/- 6.4 vs 13.6 +/- 5.2 mm, P <
      0.001). However, there was no difference in length of the infraportal type right
      posterior bile duct. The percentage of negative radial and distal common bile
      duct margins was similar, but the percentage of negative right posterior bile
      duct margins was significantly higher in trisectionectomy than in hepatectomy
      (97.7% vs 89.6%, P = 0.027). Overall, R0 resection was achieved in 84.9% of
      patients with trisectionectomy and in 70.4% of patients with hepatectomy (P =
      0.019). Survival rates were similar between patients with trisectionectomy and
      those with hepatectomy (36.8% vs 34.0% at 5-year), despite the fact that the
      former had more advanced disease. CONCLUSIONS: Left trisectionectomy for
      perihilar cholangiocarcinoma, although technically demanding, can be performed
      with similar mortality rates as left hepatectomy. From an oncologic viewpoint,
      this operation can increase the number of negative proximal ductal margins,
      leading to a high proportion of R0 resection, and, in turn, to improved survival
      rates of patients with advanced left-sided perihilar cholangiocarcinoma.

PMID- 22367445
TI  - Open versus laparoscopic resection of primary tumor for incurable stage IV
      colorectal cancer: a large multicenter consecutive patients cohort study.
AB  - OBJECTIVE: To investigate the hypothesis that laparoscopic primary tumor
      resection is safe and effective when compared with the open approach for
      colorectal cancer patients with incurable metastases. BACKGROUND: There are only
      a few reports with small numbers of patients on laparoscopic tumor resection for
      stage IV colorectal cancer. METHODS: Data from consecutive patients who underwent
      palliative primary tumor resection for stage IV colorectal cancer between January
      2006 and December 2007 were collected retrospectively from 41 institutions. Short
      and long-term outcomes were compared between patients who underwent laparoscopic
      or open resection. RESULTS: A total of 904 patients (laparoscopic group: 226,
      open group: 678) with a median age of 64 years (range: 22-95) were included in
      the analysis. Conversion was required in 28 patients (12.4%) and the most common
      reasons for conversion (23/28: 82%) were bulky or invasive tumors. There was no
      30-day postoperative mortality in either group. The complication rate (NCI-CTCAE
      grade 2-4) after laparoscopic surgery (17%) was significantly lower than that
      after open surgery (24%) (P = 0.02), and the difference was greater (4% vs 12%; P
      < 0.001) when we limited the analysis to severe (>=grade 3) complications. The
      median length of postoperative hospital stay in the laparoscopic group was
      significantly shorter than that in the open group (14 vs 17 days; P = 0.002). In
      univariate analysis, overall survival for the laparoscopic group was
      significantly better than that for open surgery (median survival time: 25.9 vs
      22.3 months, P = 0.04), although no difference was apparent in multivariate
      analysis. CONCLUSIONS: Compared with open surgery, laparoscopic primary tumor
      resection has advantages in the short term and no disadvantages in the long term.
      It is a reasonable treatment option for certain stage IV colorectal cancer
      patients with incurable disease.

PMID- 22367446
TI  - Observational teamwork assessment for surgery: feasibility of clinical and
      nonclinical assessor calibration with short-term training.
AB  - OBJECTIVES: To assess the feasibility of training clinical and nonclinical novice
      assessors to rate teamwork behavior in the operating room with short-term
      structured training using the observational teamwork assessment for surgery
      (OTAS) tool. BACKGROUND: Effective teamwork is fundamental to the delivery of
      optimal patient care in the operating room (OR). OTAS provides a comprehensive
      and robust measure of teamwork in surgery. To date, assessors with a background
      in psychology/human factors have been shown to be able to use OTAS reliably after
      training. However, the feasibility of observer training over a short timescale
      and accessibility to the wider clinical community (ie, OTAS use by clinicians)
      are yet to be empirically demonstrated. METHODS: Ten general surgery cases were
      observed and assessed using OTAS in real-time by an expert in rating OTAS
      behaviors (100+ cases rated) and 4 novices: 2 psychologists and 2 surgeons.
      Assessors were blinded to each other's scores during observations. After each
      observation, scores were compared and discussed between expert and novice
      assessors in a debriefing session. RESULTS: All novices were reliable with the
      expert to a acceptable degree at rating all OTAS behaviors by the end of training
      (intraclass correlation coefficients >=0.68). For 3 of the 5 behaviors
      (communication, cooperation, and leadership), calibration improved most rapidly
      across the first 7 observed cases. For monitoring/situational awareness,
      calibration improved steadily across the 10 observed cases. For coordination, no
      significant improvement in calibration over time was observed because of high
      interrater reliability from the outset (ie, a ceiling effect). There was no
      significant difference between surgeons and psychologists in their calibration
      with the expert. CONCLUSIONS: It is feasible to train both clinicians and
      nonclinicians to use OTAS to assess teamwork behaviors in ORs over a short
      structured training period. OTAS is an accessible tool that can be used robustly
      (ie, reliably) by assessors from both clinical and nonclinical backgrounds.

PMID- 22367447
TI  - A proposal for enhancing the general surgical workforce and access to surgical
      care.
AB  - OBJECTIVE(S): The goals of this focused meeting were to verify and clarify the
      causes and extent of the general surgery (GS) workforce shortfalls. We also
      sought to define workable solutions within the existing framework of medical
      accreditation and certification. BACKGROUND: Numerous peer-reviewed and lay
      reports describe a current and worsening availability of GS services, affecting
      rural areas as well as large cities, academia, and the military. METHOD: Primary
      recommendations were broadly agreed upon by attendee surgeons who were selected
      from numerous different professional scenarios and included 2 nonmedical
      observers. RESULTS:  RECOMMENDATIONS: (1) enhance the number of GS trainees and
      the breadth of training, (2) incorporate more flexibility and breadth in
      residency, (3) minimally invasive surgery should largely return to GS, (4)
      broader use of community hospitals in these efforts, (5) publicize loan
      forgiveness and improved visa status for international medical graduates going
      into GS, and (6) select candidates with a bias toward a general surgical career.
      CONCLUSION: These methods are promising approaches to this serious deficiency but
      will require regular reporting and publicity for the recording of actual
      increases in GS output.

PMID- 22367449
TI  - The health and well-being of American surgery.

PMID- 22367448
TI  - Circulating intestinal fatty acid-binding protein as an early marker of
      intestinal necrosis after aortic surgery: a prospective observational cohort
      study.
AB  - OBJECTIVE: This study evaluated the usefulness of plasma intestinal fatty-acid
      binding protein (IFABP) levels in the early identification of intestinal necrosis
      (IN) in patients undergoing different types of aortic surgery. BACKGROUND:
      Intestinal compromise greatly contributes to postoperative adverse outcome. IN is
      the most detrimental form of intestinal compromise and is notoriously difficult
      to diagnose. IFABP is a small protein exclusively expressed by mature enterocytes
      and a promising marker of intestinal damage. METHODS: Plasma IFABP concentrations
      were measured in blood samples taken perioperatively from 55 patients undergoing
      open thoracic or thoracoabdominal aneurysm repair [OR-TAA(A)], 25 patients
      undergoing conventional open abdominal aneurysm repair (OR-abdominal aortic
      aneurysm [AAA]), and 16 patients undergoing endovascular aneurysm repair (EVAR).
      Data were compared with perioperative changes in arterial pH and serum lactate
      levels. RESULTS: IFABP levels increased in all patients undergoing OR-TAA(A) and
      OR-AAA reaching peak levels shortly after surgery; 281 +/- 33 to 2,298 +/- 490
      pg/mL (P < 0.001) and 187 +/- 31 to 641 +/- 176 pg/mL (P < 0.05) respectively.
      IFABP levels were significantly higher in patients undergoing OR-TAA(A) (P <
      0.001). IFABP levels in EVAR patients remained at baseline concentrations
      throughout the study. Four patients [2 OR-AAA, 2 OR-TAA(A)] developed fatal
      postoperative intestinal ischemia on day 2 or 3. High levels of plasma IFABP at
      the end of surgery had 100% sensitivity and 98.1% specificity for the
      identification of patients developing IN. In OR-AAA patients, arterial pH and
      lactate levels were of additional discriminating value. Complete discrimination
      between patients with and without IN using plasma IFABP could be made on the
      first postoperative day. CONCLUSIONS: Analysis of plasma IFABP levels is of
      additional value to other current plasma markers in the diagnosis of IN, and it
      enables early identification of patients with IN after aortic surgery days before
      clinical diagnosis.

PMID- 22367450
TI  - [Sonography in internal medicine].

PMID- 22367451
TI  - Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff
      mice.
AB  - Sandhoff Disease (SD) involves the CNS accumulation of ganglioside GM2 and asialo
      GM2 (GA2) due to inherited defects in the beta-subunit gene of beta
      hexosaminidase A and B (Hexb gene). Substrate reduction therapy, utilizing imino
      sugar N-butyldeoxygalactonojirimycin (NB-DGJ), reduces ganglioside biosynthesis
      and levels of stored GM2 in SD mice. Intracranial transplantation of Neural Stem
      Cells (NSCs) can provide enzymatic cross correction, to help reduce ganglioside
      storage and extend life. Here we tested the effect of NSCs and NB-DGJ, alone and
      together, on brain beta-hexosaminidase activity, GM2, and GA2 content in juvenile
      SD mice. The SD mice received either cerebral NSC transplantation at post-natal
      day 0 (p-0), intraperitoneal injection of NB-DGJ (500 mg/kg/day) from p-9 to p
      15, or received dual treatments. The brains were analyzed at p-15. beta
      galactosidase staining confirmed engraftment of lacZ-expressing NSCs in the
      cerebral cortex. Compared to untreated and sham-treated SD controls, NSC
      treatment alone provided a slight increase in Hex activity and significantly
      decreased GA2 content. However, NSCs had no effect on GM2 content when analyzed
      at p-15. NB-DGJ alone had no effect on Hex activity, but significantly reduced
      GM2 and GA2 content. Hex activity was slightly elevated in the NSC + drug-treated
      mice. GM2 and GA2 content in the dual treated mice were similar to that of the NB
      DGJ treated mice. These data indicate that NB-DGJ alone was more effective in
      targeting storage in juvenile SD mice than were NSCs alone. No additive or
      synergistic effect between NSC and drug was found in these juvenile SD mice.

PMID- 22367452
TI  - Families' experience of oncogenetic counselling: accounts from a heterogeneous
      hereditary cancer risk population.
AB  - This paper reports the results of semi-structured family interviews conducted
      with a purposive sample of nine families (comprising 50 individuals) involved in
      cancer genetic counselling at a Portuguese public hospital. Qualitative analysis
      resulted in thematic categories illustrating: (1) how families go through cancer
      genetic counselling (eliciting risk awareness, the motivators, risk management,
      the psychosocial context of familial engagement in genetic counselling, and the
      familial pathways of cancer risk tracking); and (2) how families incorporate
      genetic risk into family life (strategies for family resilience, and the meanings
      and values that permeate the experience). Families have recognised the value of
      genetic counselling in enabling participants to take measures to confront disease
      risk; however, the experience was dominated by distressing feelings. A set of
      ethical-relational principles guided the experience. Familial experiences on
      genetic counselling and tracking of cancer susceptibility encompass a sense of
      trajectory that takes the form of an historical and intergenerational narrative
      process, linking past, present and possible futures. Such process implies an
      ongoing set of individual and interactional experiences taking place over time.
      Specific changes associated with the illness timeline and with individual and
      family developmental lifespan transitions are thus acknowledged. These results
      may help genetics healthcare practitioners understand how families perceive,
      respond to and accommodate cancer risk counselling, and thus illuminate family
      oriented tenets for planning and practice.

PMID- 22367453
TI  - Diagnostic pitfalls in interpreting cranial CT following cardiac angiography.

PMID- 22367454
TI  - The influence of gene-environment interactions on the development of alcoholism
      and drug dependence.
AB  - Alcoholism and drug dependence are common psychiatric disorders with a
      heritability of about 50%; therefore genetic and environmental influences are
      equally important. Early-life stress is a predictor of adolescent problem
      drinking/drug use and alcohol/drug dependence in adulthood, but moderating
      factors governing the availability of alcohol/drug are important. The risk
      resilience balance for addiction may be due in part to the interaction between
      genetic variation and environment stressors (G * E); this has been confirmed by
      twin studies of inferred genetic risk. Measured genotype studies to detect G * E
      effects have used a range of alcohol consumption and diagnostic phenotypes and
      stressors ranging from early-life to adulthood past year life events. In this
      article, the current state of the field is critically reviewed and suggestions
      are put forth for future research.

PMID- 22367455
TI  - A robotic device as a sensitive quantitative tool to assess upper limb
      impairments in stroke patients: a preliminary prospective cohort study.
AB  - OBJECTIVE: To compare kinematic indices in age-matched healthy subjects and
      stroke patients, by evaluating various tasks performed with a robotic device, and
      to provide an objective and standardized protocol to assess upper limb
      impairments in stroke patients. DESIGN: A prospective cohort study. SUBJECTS: Age
      matched healthy subjects (n = 10) and stroke patients (n = 10). METHODS: Various
      kinematic indices were analysed from 3 randomly assigned tasks performed by the
      affected arm in stroke patients and the dominant arm in healthy subjects. These
      tasks, composed of large-amplitude, targeted and geometrical movements, were
      standardized and performed with the ReaPLAN robotic device. RESULTS: For large
      amplitude movements, the stroke patients' path lengths were less constant in
      amplitude, less rectilinear and less smooth than those for healthy subjects (p <
      0.001). For the targeted movements, the stroke patients' path lengths were less
      rectilinear than those of the healthy subjects (p < 0.001). For the geometrical
      movements, the stroke patients had greater difficulty making the requested shapes
      compared with the healthy subjects (p < 0.01). CONCLUSION: Our study proposes an
      objective and standardized protocol to assess stroke patients' upper limbs with
      any robotic device. We suggest that further randomized controlled trials could
      use this quantitative tool to assess the efficacy of treatments such as robot
      assisted therapy.

PMID- 22367456
TI  - Adherence to HIV treatment guidelines for comorbid disease assessment and
      initiation of antiretroviral therapy.
AB  - BACKGROUND: There are limited data on adherence to HIV treatment guidelines. We
      assessed adherence to US Department of Health and Human Services guidelines with
      Australian Commentary for adults initiating antiretroviral therapy (ART).
      METHODS: Data were recorded regarding "when to start", "what to start" and pre
      ART comorbid disease assessment for consecutive adults initiating ART at primary
      care and hospital clinics in Sydney and Melbourne from 2004 through 2008.
      Independent predictors of adherence to guidelines were calculated by stepwise
      logistic regression. RESULTS: For the 500 subjects (95.9% male, mean 40.2 years,
      median CD4 count 270 cells/MUL) "when to start" adherence was 87.6%, and was less
      likely with initiation in a clinical trial [0.25 (95% CI: 0.13 to 0.49); P <
      0.0001] and previous, short-term nontherapeutic antiretroviral exposure [0.08
      (0.03 to 0.25); P < 0.0001]. "What to start" adherence was 69.0% for guideline
      "preferred" regimens (85.8% for guideline-"preferred" or "alternative" regimens)
      and more likely with ART initiated in 2008 versus pre-2008 [OR: 2.69 (1.64 to
      4.61); P = 0.0001]. Median comorbid disease assessment adherence was 56.8%,
      ranging from 25.6% for urinalysis to 99.2% for white blood cell count, and was
      more likely in patients with AIDS, and initiating ART in hospital or in a
      clinical trial. Hospital clinics were more likely to perform antiretroviral
      resistance testing (71.2% vs. 46.4%, P < 0.0001), to use "preferred" ART regimens
      (76.8% vs. 62.2%, P = 0.0002) but less likely to promote healthy diet and
      lifestyle (63.4% vs. 36.4%, P < 0.0001). CONCLUSIONS: "When to start" and "what
      to start" guidelines have been largely adhered to in Australia, but pre-ART
      comorbid disease assessment requires greater attention.

PMID- 22367457
TI  - Urgent ureteroscopy as first-line treatment for ureteral stones: a meta-analysis
      of 681 patients.
AB  - There are various recent studies on the use of ureteroscopy and debate on whether
      this should be the first-line treatment for patients with ureteral stones. The
      aim of this meta-analysis was to understand the role of this surgical procedure
      in the emergency setting as first-line treatment and to compare the immediate
      procedure with a delayed one in terms of stone-free rate and complications. A
      bibliographic search covering the period from January 1980 to March 2010 was
      conducted in PubMed, MEDLINE and EMBASE. This analysis is based on the six
      studies found that fulfilled the predefined inclusion criteria. A total of 681
      participants were included. The number of participants in each of the studies
      considered ranged from 27 to 244 (mean 113). Stone-free rates were 81.9% (72.0
      91.8) for the proximal ureter, 87.3% (82.6-92.0) for the mid-ureter, 94.9% (92.1
      97.6) for the distal ureter and 89.5% (86.5-92.5) overall according to the
      logistic regression applied. These values are not statistically significantly
      different from those reported in the AUA and EAU guidelines. The stone diameter
      seems to affect the stone-free rate. An increase of the stone diameter of 1 mm
      beyond 8 mm corresponded to a reduction of stone-free rate of 5% (2.4-8.0) and
      8.1% (3.8-12.1) for the distal and proximal ureters, respectively. There is a
      complete lack of information in international guidelines on the ureteroscopic
      management of ureteral stones in an emergency setting and the currently available
      results are dispersed in a few studies in the literature. The rationale for using
      emergency ureteroscopy is more rapid stone clearance and relief from colic pain.
      According to our meta-analysis, immediate ureteroscopy for ureteral stone colic
      seems to be a safe treatment with a high success rate. This evidence will be
      validated by further randomized studies, with larger series of patients.

PMID- 22367458
TI  - "Re: Radiation protection in pediatric radiology".

PMID- 22367459
TI  - Genetic basis of destruxin production in the entomopathogen Metarhizium
      robertsii.
AB  - Destruxins are among the most exhaustively researched secondary metabolites of
      entomopathogenic fungi, yet definitive evidence for their roles in pathogenicity
      and virulence has yet to be shown. To establish the genetic bases for the
      biosynthesis of this family of depsipeptides, we identified a 23,792-bp gene in
      Metarhizium robertsii ARSEF 2575 containing six complete nonribosomal peptide
      synthetase modules, with an N-methyltransferase domain in each of the last two
      modules. This domain arrangement is consistent with the positioning of the
      adjacent amino acids N-methyl-L: -valine and N-methyl-L: -alanine within the
      depsipeptide structure of destruxin. DXS expression levels in vitro and in vivo
      exhibited comparable patterns, beginning at low levels during the early growth
      phases and increasing with time. Targeted gene knockout using Agrobacterium
      mediated transformation produced mutants that failed to synthesize destruxins, in
      comparison with wild type and ectopic control strains, indicating the involvement
      of this gene in destruxin biosynthesis. The destruxin synthetase (DXS) disruption
      mutant was as virulent as the control strain when conidial inoculum was topically
      applied to larvae of Spodoptera exigua, Galleria mellonella, and Tenebrio molitor
      indicating that destruxins are dispensable for virulence in these insect hosts.
      The DXS mutants exhibited no other detectable changes in morphology and
      development.

PMID- 22367460
TI  - Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-alpha via the
      PI3K/Akt and MAPK signaling pathways.
AB  - The kallikrein-kinin system (KKS) is a complex multi-enzyme system which is
      composed of circulating and tissue kallikrein and kinin. It is well established
      that tissue kallikrein and kinin play crucial and diverse roles in cardiovascular
      and renal homeostasis. Recent data indicate that kallikrein gene delivery reduces
      insulin resistance in STZ-treated rats suggesting a protective role for kinin in
      the development of diabetes. This study investigated the effects of exogenous
      bradykinin (BK) on the apoptosis of NIT-1 cells, a pancreatic beta-cell line in
      vitro. Exogenous BK significantly protected NIT-1 cells from TNF-alpha-induced
      apoptosis. These effects were associated with upregulation of Bcl-2 and Bcl-xL
      protein expression levels as well as with downregulation of Bax expression levels
      via the activation of the mitogen-activated protein kinase and PI3K/Akt signaling
      pathways. In conclusion, these data highlight the beneficial roles of BK on
      pancreatic beta-cell function.

PMID- 22367461
TI  - Hyoid expansion as a treatment for obstructive sleep apnea: a pilot study.
AB  - OBJECTIVES: Hyoid expansion is a novel procedure that was developed to widen and
      stabilize the lateral walls of the hypopharynx in order to improve obstructive
      sleep apnea. This study was conducted to evaluate the safety, efficacy and
      feasibility of hyoid expansion. STUDY DESIGN: A prospective, non-randomized
      multicenter pilot study with a follow-up of 6 months was conducted. METHOD: An
      implantable device (the Air-Frame system) was used to surgically expand the hyoid
      bone. Subjective and objective outcome measures were evaluated. RESULTS: The
      procedure was successfully performed in all patients without technical adverse
      events. There were three clinical adverse events, and tolerance was good.
      Although there was a significant improvement in snoring and excessive daytime
      sleepiness, there was no objective improvement of the apnea-hypopnea index as
      measured by polysomnography. CONCLUSION: Hyoid expansion did not provide
      objective improvement of obstructive outcome measures in patients with
      obstructive sleep apnea syndrome.

PMID- 22367463
TI  - Polymeric assemblies and nanoparticles with stimuli-responsive fluorescence
      emission characteristics.
AB  - Fluorescent polymeric assemblies and nanoparticles (NPs) of nanoscale dimensions
      have become a focus of intensive investigations during the past few decades due
      to combined advantages such as improved biocompatibility, water dispersibility,
      stimuli-responsiveness, facile integration into optical detection devices, and
      the ability of further functionalization. In addition, the chemical composition
      and morphology of polymeric assemblies and NPs can be modulated via synthetic
      approaches, leading to the precise spatial organization of multiple fluorophores.
      Thus, polymeric assemblies and NPs have been utilized to optimize the
      photoluminescent properties of covalently or physically attached fluorophores and
      facilely modulate the fluorescence resonance energy transfer (FRET) processes
      when the polymeric matrix is endowed with stimuli-responsiveness. These
      fascinating fluorescent polymeric assemblies and NPs offer unique and versatile
      platforms for the construction of novel detection, imaging, biolabeling, and
      optoelectronic systems. This feature article focuses on the recent developments
      of polymeric assemblies and NPs-based stimuli-tunable fluorescent systems and
      highlights their future practical applications with selected literature reports.

PMID- 22367462
TI  - Cyclic alternating pattern analysis in REM sleep behavior disorder.
AB  - OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a type of
      REM parasomnia characterized by complex motor activity during REM sleep. In this
      study, cyclic alternating pattern (CAP) in patients with idiopathic RBD was
      analyzed to evaluate the expression of arousal instability of NREM sleep.
      METHODS: A total of 31 idiopathic RBD patients and age- and gender-matched 21
      control subjects were consecutively recruited. Conventional sleep
      polysomnographic recording parameters and CAP parameters were compared between
      RBD and the control group. RESULTS: The number of CAP cycles (120.13 +/- 113.56,
      p = 0.007), CAP sequences (20.9 +/- 18.15, p < 0.001), CAP index (25.14 +/-
      24.44, p = 0.017), and CAP rate (24.07 +/- 13.22, p = 0.016) were all
      significantly higher in RBD patients compared to the control group. The increase
      in CAP sequences was observed in phase A2 and A3 subtypes while phase A1 subtype
      was significantly lower in RBD patients. A significant positive correlation was
      observed between disease duration with total CAP time (r = 0.289, p = 0.042) and
      A3 index (r = 0.32, p = 0.024). There was a negative correlation between the age
      and A1 index (r = -0.4491, p = 0.0001). CONCLUSION: To our knowledge this is the
      first polysomnographic clinical study which evaluated CAP parameters in RBD.
      Increased CAP rate found may be considered as a sign showing that NREM sleep may
      also be affected in RBD patients. Therefore, CAP analysis may be important to
      enlighten the pathogenesis of parasomnias.

PMID- 22367464
TI  - Aluminum and sulphate removal by a highly Al-resistant dissimilatory sulphate
      reducing bacteria community.
AB  - A highly Al-resistant dissimilatory sulphate-reducing bacteria community was
      isolated from sludge of the wetland of Urgeirica mine (community W). This
      community showed excellent sulphate removal at the presence of Al3+. After 27
      days of incubation, 73, 86 and 81% of sulphate was removed in the presence of
      0.48, 0.90 and 1.30 mM of Al3+, respectively. Moreover, Al3+ was simultaneously
      removed: 55, 85 and 78% of metal was removed in the presence of 0.48, 0.90 and
      1.30 mM of Al3+, respectively. The dissociation of aluminium-lactate soluble
      complexes due to lactate consumption by dissimilatory sulphate-reducing bacteria
      can be responsible for aluminum removal, which probably precipitates as insoluble
      aluminium hydroxide. Phylogenetic analysis of 16S rRNA gene showed that this
      community was mainly composed by bacteria closely related to Desulfovibrio
      desulfuricans. However, bacteria affiliated to Proteus and Ralstonia were also
      present in the community.

PMID- 22367465
TI  - Degradation of nitrocellulose-based paint by Desulfovibrio desulfuricans ATCC
      13541.
AB  - Nitrocellulose is one of the most commonly used compounds in ammunition and paint
      industries and its recalcitrance to degradation has a negative impact on human
      health and the environment. In this study the capability of Desulfovibrio
      desulfuricans ATCC 13541 to degrade nitrocellulose as binder in paint was assayed
      for the first time. Nitrocellulose-based paint degradation was followed by
      monitoring the variation in nitrate, nitrite and ammonium content in the culture
      medium using Ultraviolet-Visible spectroscopy. At the same time cell counts and
      ATP assay were performed to estimate bacterial density and activity in all
      samples. Infrared spectroscopy and colorimetric measurements of paint samples
      were performed to assess chemical and colour changes due to the microbial action.
      Microscope observations of nitrocellulose-based paint samples demonstrated the
      capability of the bacterium to adhere to the paint surface and change the paint
      adhesive characteristics. Finally, preliminary studies of nitrocellulose
      degradation pathway were conducted by assaying nitrate- and nitrite reductases
      activity in D. desulfuricans grown in presence or in absence of paint. We found
      that D. desulfuricans ATCC 13541 is able to transform nitrocellulose as paint
      binder and we hypothesised ammonification as degradation pathway. The results
      suggest that D. desulfuricans ATCC 13541 is a good candidate as a nitrocellulose
      degrading bacterium.

PMID- 22367466
TI  - Stand-alone cervical cages versus anterior cervical plate in 2-level cervical
      anterior interbody fusion patients: clinical outcomes and radiologic changes.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: To compare the efficacy of 2-level
      anterior cervical discectomy and fusion with cage alone (ACDF-CA) and with cage
      and plate construct (ACDF-CPC) with regard to clinical outcome and radiologic
      changes. SUMMARY OF BACKGROUND DATA: The use of stand-alone cervical interbody
      cages in ACDF has become popular, but high subsidence rates have been reported in
      the literature. METHODS: A total of 54 consecutive patients who underwent 2-level
      ACDF-CA or ACDF-CPC after suffering from cervical radiculopathy were divided into
      2 groups: group A (n = 28) underwent ACDF-CA, group B (n = 26) underwent ACDF
      CPC. Fusion rate, global and segmental kyphosis, disk height, and subsidence rate
      were assessed by radiolographs. Clinical outcomes were assessed using Robinson's
      criteria. RESULTS: Solid fusion was achieved in 96.43% (27/28) in group A and in
      96.15% (25/26) in group B. Fusion segmental kyphosis of >5 degrees occurred in
      14.29% (4/28) of group A and in 7.69% (2/26) of group B; however, there was no
      statistical difference between the 2 groups (P>0.05). Subsidence occurred in
      35.71% (10/28) of group A as compared with 11.54% (3/26) of group B (P<0.05).
      Clinical outcomes were similar in the 2 treatment groups. CONCLUSIONS: The use of
      cage and plate construct in 2-level ACDF results in a shorter fusion duration and
      a lower subsidence rate than that of cage alone; however, there is no significant
      difference in the postoperative global and segmental alignment and clinical
      outcomes between groups.

PMID- 22367467
TI  - Impact of multimodal intraoperative monitoring during surgery for spine deformity
      and potential risk factors for neurological monitoring changes.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the efficacy of
      multimodal intraoperative neuromonitoring for predicting iatrogenic neurological
      injury during surgical correction of a spine deformity and evaluate the potential
      risk factors for neurological monitoring changes. SUMMARY OF BACKGROUND DATA:
      Single modal intraoperative neuromonitoring is insufficient to predict
      neurological injury during surgical correction of spine deformity. Multimodal
      monitoring can provide more accuracy. Some risk factors were reported to be
      correlated with high rates of neurological deficits during scoliosis correction.
      But few studies have reported on the risk factors for neurological monitoring
      changes (NMCs). METHODS: The records of 176 consecutive patients who underwent
      surgery for the treatment of spinal deformities were reviewed. The patients were
      monitored using transcranial electric motor-evoked potential (MEP) and/or
      somatosensory-evoked potential (SEP). Alterations with the MEP wave amplitude
      decreasing more than 75% and SEP amplitude decreasing more than 50%, as compared
      with the baseline, were diagnosed as positive changes. Risk factors related to
      NMCs were evaluated, in light of preoperative neurological deficits, comorbidity
      of spinal cord deformity, procedure of osteotomy, main curve Cobb angle, and a
      diagnosis of kyphosis. RESULTS: Combined MEP/SEP monitoring was successfully
      achieved in 175 of 176 cases. Eleven cases were presented with true NMCs
      according to MEPs. One patient had an irreversible neurological deficit and 4
      patients had transient neurological deficits after waking up from the operation.
      SEP lagged MEP for an average of 15 minutes when both were presented with
      positive changes. The sensitivity and specificity of MEP were 91.7% and 98.8%,
      respectively. Solo SEP were 50% and 95.2%. Combined MEP and SEP were 92.9% and
      99.4%. The procedure of osteotomy, curve Cobb angle more than 90 degrees, and
      preoperative kyphosis were correlated with a higher incidence of NMCs.
      CONCLUSIONS: Multimodal intraoperative monitoring provides higher sensitivity for
      monitoring during spine deformity surgery and can predict events of neurological
      injury. The detection of NMCs and adjustment of surgical strategy may prevent
      irreversible neurological deficits. The possible risk factors for NMCs during
      spine deformity surgery include an osteotomy procedure, kyphosis correction, and
      preoperative Cobb angle more than 90 degrees.

PMID- 22367468
TI  - Current status and guidelines for the assessment of tumour vascular support with
      dynamic contrast-enhanced computed tomography.
AB  - Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular
      support of tumours through analysis of temporal changes in attenuation in blood
      vessels and tissues during a rapid series of images acquired with intravenous
      administration of iodinated contrast material. Commercial software for DCE-CT
      analysis allows pixel-by-pixel calculation of a range of validated physiological
      parameters and depiction as parametric maps. Clinical studies support the use of
      DCE-CT parameters as surrogates for physiological and molecular processes
      underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of
      drug action in early phase trials for the treatment of a range of cancers. DCE-CT
      can be appended to current imaging assessments of tumour response with the
      benefits of wide availability and low cost. This paper sets out guidelines for
      the use of DCE-CT in assessing tumour vascular support that were developed using
      a Delphi process. Recommendations encompass CT system requirements and quality
      assurance, radiation dosimetry, patient preparation, administration of contrast
      material, CT acquisition parameters, terminology and units, data processing and
      reporting. DCE-CT has reached technical maturity for use in therapeutic trials in
      oncology. The development of these consensus guidelines may promote broader
      application of DCE-CT for the evaluation of tumour vascularity. Key Points * DCE
      CT can robustly assess tumour vascular support * DCE-CT has reached technical
      maturity for use in therapeutic trials in oncology * This paper presents
      consensus guidelines for using DCE-CT in assessing tumour vascularity.

PMID- 22367469
TI  - A proposal for combined MRI and PET/CT interpretation criteria for preoperative
      nodal staging in non-small-cell lung cancer.
AB  - OBJECTIVES: To determine the positive reading criteria for malignant nodes when
      interpreting combined MRI and PET/CT images for preoperative nodal staging in non
      small-cell lung cancer (NSCLC). METHODS: Forty-nine patients with biopsy-proven
      NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)].
      Each nodal station was evaluated for the presence of metastasis by applying
      either inclusive (positive if either one read positive) or exclusive (positive if
      both read positive) criteria in the combined interpretation of PET/CT and MRI.
      Nodal stage was confirmed pathologically. The combined diagnostic accuracy of
      PET/CT and MRI was determined on per-nodal station and per-patient bases and
      compared with that of PET/CT alone. RESULTS: In 49 patients, 39 (19%) of 206
      nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%)
      had concordant readings, while the rest (10%) had discordant readings. Inclusive
      criteria of combined PET/CT and MRI helped increase sensitivity for detecting
      nodal metastasis (69%) compared with PET/CT alone (46%; P = 0.003), while
      specificity was not significantly decreased. CONCLUSION: Inclusive criteria in
      combined MRI and PET/CT readings help improve significantly the sensitivity for
      detecting nodal metastasis compared with PET/CT alone and may decrease
      unnecessary open thoracotomy. Key Points * Combined interpretation of MRI and
      PET/CT enhances the detection of nodal metastasis. * Inclusive criteria of
      combined MRI/PET/CT improved the sensitivity for detecting nodal metastasis. *
      Combined interpretation of MRI and PET/CT may reduce unnecessary open
      thoracotomies.

PMID- 22367471
TI  - Diffusion weighted imaging of the normal breast: reproducibility of apparent
      diffusion coefficient measurements and variation with menstrual cycle and
      menopausal status.
AB  - OBJECTIVES: To establish the reproducibility of apparent diffusion coefficient
      (ADC) measurements in normal fibroglandular breast tissue and to assess variation
      in ADC values with phase of the menstrual cycle and menopausal status. METHODS:
      Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic
      resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC(total)
      and a perfusion-insensitive ADC(high) (omitting b = 0) were calculated.
      Reproducibility and inter-observer variability of mean ADC values were assessed.
      The difference in mean ADC values between the two phases of the menstrual cycle
      and the postmenopausal breast were evaluated. RESULTS: ADC(total) and ADC(high)
      showed good reproducibility (r% = 17.6, 22.4). ADC(high) showed very good inter
      observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC)
      were 0.93 and 0.91. Mean ADC values were significantly lower in the
      postmenopausal breast (ADC(total) 1.46 +/- 0.3 * 10(-3) mm(2)/s, ADC(high) 1.33
      +/- 0.3 * 10(-3) mm(2)/s) compared with the premenopausal breast (ADC(total) 1.84
      +/- 0.26 * 10(-3) mm(2)/s, ADC(high) 1.77 +/- 0.26 * 10(-3) mm(2)/s; both P <
      0.001). No significant difference was seen in ADC values in relation to menstrual
      cycle (ADC(total) P = 0.2, ADC(high) P = 0.24) or between postmenopausal women
      taking or not taking oestrogen supplements (ADC(total) P = 0.6, ADC(high) P =
      0.46). CONCLUSIONS: ADC values in fibroglandular breast tissue are reproducible.
      Lower ADC values within the postmenopausal breast may reduce diffusion-weighted
      contrast and have implications for accurately detecting tumours. KEY POINTS: *
      ADC values from fibroglandular breast tissue are measured reproducibly by
      multiple observers. * Mean ADC values were significantly lower in postmenopausal
      than premenopausal breast tissue. * Mean ADC values did not vary significantly
      with menstrual cycle. * Low postmenopausal ADC values may hinder tumour detection
      on DW-MRI.

PMID- 22367470
TI  - MRI of the breast in patients with DCIS to exclude the presence of invasive
      disease.
AB  - OBJECTIVES: Core biopsy underestimates invasion in more than 20% of patients with
      preoperatively diagnosed ductal carcinoma in situ (DCIS) without evidence of
      invasion (pure DCIS). The aim of the current study was to evaluate the efficacy
      of preoperative magnetic resonance imaging (MRI) to discriminate between patients
      with DCIS who are at high risk of invasive breast cancer and patients at low
      risk. METHODS: One hundred and twenty-five patients, preoperatively diagnosed
      with pure DCIS (128 lesions; 3 bilateral) by core-needle biopsy, were
      prospectively included. Clinical, mammographic, histological (core biopsy) and
      MRI features were assessed. All patients underwent breast surgery. Analyses were
      performed to identify features associated with presence of invasion. RESULTS:
      Eighteen lesions (14.1%) showed invasion on final histology. Seventy-three
      lesions (57%) showed suspicious enhancement on MRI with a type 1 (n = 12, 16.4%),
      type 2 (n = 19, 26.0%) or type 3 curve, respectively (n = 42, 57.5%). At
      multivariate analysis, the most predictive features for excluding presence of
      invasive disease were absence of enhancement or a type 1 curve on MRI (negative
      predictive value 98.5%; A(Z) 0.80, P = 0.00006). CONCLUSION: Contrast medium
      uptake kinetics at MRI provide high negative predictive value to exclude presence
      of invasion and may be useful in primary surgical planning in patients with a
      preoperative diagnosis of pure DCIS. KEY POINTS: It is important to determine
      invasion in breast DCIS. * MRI contrast medium uptake kinetics can help exclude
      the presence of invasion. * However, the positive predictive value for the
      presence of invasion is limited. * MRI features were more accurate at predicting
      invasion than mammographic features alone.

PMID- 22367472
TI  - Sonoelastography techniques in the evaluation and diagnosis of parotid neoplasms.
AB  - Ultrasound is the first-line imaging investigation in the evaluation of parotid
      gland lesions; however, ultrasound alone cannot differentiate between benign and
      malignant lesions. An imaging technique with this capability would be of great
      value, as fine needle aspiration cytology (FNAC) is not always accurate and
      partial/total parotidectomy is associated with facial nerve palsy and Frey's
      syndrome. Sonoelastography is a novel imaging technique that has been employed in
      the research setting in the evaluation of tissues including breast, thyroid,
      prostate and the salivary glands. More recently it has been used as a diagnostic
      adjunct in the sonographic evaluation of major salivary gland lesions. This
      review article outlines the current role of sonoelastography in the diagnostic
      imaging of parotid lesions, with particular reference to the findings of two
      research papers published in European Radiology. These papers employ slightly
      different techniques: the first utilises shear wave elastography whilst the
      second uses real-time sonoelastography. Sonoelastography may have potential as a
      diagnostic imaging adjunct to conventional ultrasound. However, it seems likely
      that FNAC/core biopsy will continue to be necessary. Further studies to evaluate
      the reproducibility of sonoelastographic results across a range of operators and
      systems are also needed. Key Points * Ultrasound is the initial and often
      definitive investigation for parotid lesions * Ultrasound-based strain
      elastography has been attempted but offered little additional information * New
      shear wave elastographic techniques did not confer much advantage either *
      However, analysis of elastographic patterns seems to provide advantages over
      ultrasound alone.

PMID- 22367473
TI  - High-resolution ultrasound evaluation of extrinsic wrist ligaments in patients
      affected by rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate the ultrasound features of the extrinsic wrist ligaments
      in rheumatoid arthritis (RA) patients in comparison with healthy volunteers.
      METHODS: Twenty-one consecutive patients affected by RA (12 men, 9 women; mean
      age 57 +/- 14.6 years) were compared with 21 controls (12, 9; 54 +/- 12.1,
      respectively). Wrists were evaluated using ultrasound on both palmar and dorsal
      sides along each ligament, using carpal bones as references. The following
      ligaments were studied: radioscaphocapitate, radiolunotriquetral, palmar
      ulnolunate, palmar ulnotriquetral, dorsal radiotriquetral, dorsal ulnotriquetral,
      and radial collateral ligament. Ligament number and thickness were noted.
      Echotexture was rated as fibrillar, fragmented, or heterogeneous; the surface was
      rated as smooth or blurred. RESULTS: The number of palmar ulnolunate and palmar
      ulnotriquetral ligaments detected by ultrasound in patients was significantly
      lower than in controls (P = 0.031 and P = 0.037, respectively). All ligaments had
      significantly more fragmented or heterogeneous echotexture and blurred surface
      and were significantly thinner in patients than in controls (P < 0.001). No
      correlation was found between ligament thickness and RA duration or clinical
      parameters. CONCLUSIONS: Extrinsic wrist ligaments were less detectable and
      thinner in patients affected by RA compared with healthy volunteers matched for
      age and sex. Ligament thinning did not directly correlate with RA duration and
      clinical parameters. KEY POINTS: * Ultrasound is increasingly used to evaluate
      normal anatomy of extrinsic wrist ligaments. * Extrinsic wrist ligaments are
      thinner in rheumatoid arthritis patients than in controls. * Extrinsic wrist
      ligaments are less easy to detect in rheumatoid arthritis patients. * Ligament
      thinning and detectability are not related to clinical parameters.

PMID- 22367474
TI  - Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.
AB  - We aimed to investigate possible associations between systemic iron metabolism
      deficiency and Parkinson's disease, and also to research any possible
      correlations between stage of the disease and vitamin B12 and folic acid levels.
      33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and
      22 male and 20 female age- and sex-matched controls were enrolled in the study.
      Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and
      for the females, not being in the menopausal stage were considered as exclusion
      criteria. Recordings of blood samples of both groups collected after 8 h fasts
      were assessed in terms of serum iron, ferritin levels and iron-binding capacity,
      vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine
      the stage of the disease. No statistically significant difference was found with
      respect to mean serum iron, median serum ferritin levels and median serum iron
      binding capacity between the groups. A statistically significant but inverse
      correlation was found between symptoms' duration and serum iron and ferritin
      levels. There was no statistically significant difference between the groups with
      respect to vitamin B12 and folic acid levels. However, a statistically
      significant but inverse correlation was determined between the patients' vitamin
      B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses,
      serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of
      these parameters may be the cause of the progression or may be the result of it.

PMID- 22367476
TI  - A simple and efficient method to rescue very virulent infectious bursal disease
      virus using SPF chickens.
AB  - Reverse genetic systems for efficient generation of very virulent infectious
      bursal disease virus (vvIBDV) are currently limited. In this study, we have
      developed a simple and efficient way to rescue vvIBDV using SPF chickens. The
      genome of a vvIBDV strain, HLJ0504, flanked by hammerhead and hepatitis delta
      ribozyme sequences, was cloned downstream of the cytomegalovirus enhancer and the
      chicken beta-actin promoter of the vector pCAGGS. After transfection of DF-1
      cells, cell suspensions were injected into the bursa organ of three-week-old SPF
      chickens. Using this system, vvIBDV was recovered at high titers after one
      passage, and the rescued vvIBDV remained highly lethal to SPF chickens. This
      simple and efficient method to rescue vvIBDV will be a valuable tool for better
      understanding the molecular virulence determinants of vvIBDV.

PMID- 22367477
TI  - Clinical response and autonomic modulation as seen in heart rate variability in
      mechanical intermittent cervical traction: a pilot study.
AB  - OBJECTIVE: To determine the influence of mechanical intermittent cervical
      traction on the autonomic system. DESIGN: Prospective, cases series study.
      SUBJECTS: Sixteen healthy volunteers without contraindications for cervical
      traction. METHODS: Subjects received mechanical intermittent cervical  traction
      in a sitting position under two traction forces (10% and 20% of total body
      weight). Electrocardiographic and neck surface electromyographic signals were
      recorded and analysed from 3 5-min periods (before, during and after traction).
      Subjective symptoms, heart rate and heart rate variability parameters, including
      standard deviation of all normal-to-normal beat intervals, very low-frequency
      power, low-frequency power, high-frequency power, multiscale entropy, slope of
      multiscale entropy, and root mean square value of electromyography amplitude were
      statistically compared. RESULTS: This pilot study showed that using 10% body
      weight traction force was more comfortable than using 20% body weight. Only
      subtle perturbation was noted in the autonomic  system when using 20% body weight
      traction force. CONCLUSION: The response pattern of heart rate variability
      analysis in this pilot study provides some early information about individual
      discomfort in cervical traction. The autonomic modulation and the safety of
      cervical traction with other modality settings or in patients with neck pain
      require further study.

PMID- 22367475
TI  - Glial K+ clearance and cell swelling: key roles for cotransporters and pumps.
AB  - An important feature of neuronal signalling is the increased concentration of
      K(+) in the extracellular space. The K(+) concentration is restored to its
      original basal level primarily by uptake into nearby glial cells. The molecular
      mechanisms by which K(+) is transferred from the extracellular space into the
      glial cell are debated. Although spatial buffer currents may occur, their
      quantitative contribution to K(+) clearance is uncertain. The concept of spatial
      buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i)
      difficult to reconcile with the K(+) accumulation repeatedly observed in glial
      cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell
      swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried
      out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in
      combination. In brain slices and intact optic nerve, however, only the Na(+)/K(+)
      ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance.
      The glial cell swelling associated with K(+) clearance is prevented under
      conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The
      Na(+)/K(+)/Cl(-) cotransporter is activated by increased K(+) concentration and
      cotransports water along with its substrates. It thereby serves as a K(+)
      dependent molecular water pump under conditions of increased extracellular K(+)
      load.

PMID- 22367478
TI  - Disruption of mindin exacerbates cardiac hypertrophy and fibrosis.
AB  - Cardiac hypertrophy is a response of the myocardium to increased workload and is
      characterised by an increase of myocardial mass and an accumulation of
      extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an
      angiogenesis inhibitor, all of which are key players in cardiac hypertrophy,
      mindin is an attractive target for therapeutic intervention to treat or prevent
      cardiac hypertrophy and heart failure. In this study, we investigated the role of
      mindin in cardiac hypertrophy using littermate Mindin knockout (Mindin ( -/- ))
      and wild-type (WT) mice. Cardiac hypertrophy was induced by aortic banding (AB)
      or angiotensin II (Ang II) infusion in Mindin ( -/- ) and WT mice. The extent of
      cardiac hypertrophy was quantitated by echocardiography and by pathological and
      molecular analyses of heart samples. Mindin ( -/- ) mice were more susceptible to
      cardiac hypertrophy and fibrosis in response to AB or Ang II stimulation than
      wild type. Cardiac function was also markedly exacerbated during both systole and
      diastole in Mindin ( -/- ) mice in response to hypertrophic stimuli. Western blot
      assays further showed that the activation of AKT/glycogen synthase kinase 3beta
      (GSK3beta) signalling in response to hypertrophic stimuli was significantly
      increased in Mindin ( -/- ) mice. Moreover, blocking AKT/GSK3beta signalling with
      a pharmacological AKT inhibitor reversed cardiac abnormalities in Mindin ( -/- )
      mice. Our data show that mindin, as an intrinsic cardioprotective factor,
      prevents maladaptive remodelling and the transition to heart failure by blocking
      AKT/GSK3beta signalling.

PMID- 22367480
TI  - Medium modification to enhance the formation of bioactive metabolites in shake
      flask cultures of Antrodia cinnamomea by adding citrus peel extract.
AB  - Antrodia cinnamomea has recently become a well-known medicinal mushroom in
      Taiwan. Bioactive compounds found in A. cinnamomea include: polysaccharide,
      sesquiterpene lactone, steroids and triterpenoids. The aim of this study was to
      evaluate the feasibility of adding citrus peel extract to enhance the formation
      of bioactive metabolites in the submerged culture of A. cinnamomea. With the
      exception of grapefruit, citrus peel extracts tested were proved to be beneficial
      to mycelial growth and to the production of intracellular polysaccharide. Lemon
      was the most effective for enhancing bioactive metabolite production. With an
      addition of 2% (v/v), the mycelium biomass concentration and intracellular
      polysaccharide content rose from 11.96 g DW/L of the control and 123.6 mg/g DW to
      21.96 g DW/L and 230.8 mg/g DW, respectively, on day 8. The production of
      triterpenoids also increased from 86.7 to 282.9 mg/L. Moreover, this study also
      demonstrates that although the addition of peel extract could cause the
      lengthening of the exponential phase and reduce the specific growth rate, the
      production rate of biomass, intracellular polysaccharide and triterpenoids was
      still enhanced significantly.

PMID- 22367479
TI  - Interstitial lung disease in myositis: clinical subsets, biomarkers, and
      treatment.
AB  - Interstitial lung disease (ILD) is the most frequent organ involvement (found in
      nearly half) of myositis patients, but it reveals various clinical courses and
      therapeutic responsiveness according to clinical and serological subsets.
      Autoantibodies, as well as imaging and histopathological studies, are useful for
      the classification of ILD in myositis and provide useful information for
      predicting prognosis and determining treatment. Antisynthetase antibodies are
      correlated with chronic and recurrent ILD, whereas anti-CADM-140 (MDA5/IFIH1)
      antibodies are a marker of acute progressive ILD in clinically amyopathic
      dermatomyositis. Serum KL-6, SP-D, and ferritin are useful biomarkers for
      monitoring the activity and severity of ILD. Regarding treatment, glucocorticoids
      are the first-line drug, but additional immunomodulating drugs are also used in
      refractory patients. Cyclophosphamide and calcineurin inhibitors (cyclosporine
      and tacrolimus) appear to be the key drugs in the treatment of refractory
      myositis-ILD. Rituximab may become another candidate if these drugs are not
      effective.

PMID- 22367481
TI  - Association of human leukocyte antigen-DRB1 alleles with chronic hepatitis B
      virus infection in the Han Chinese of Northeast China.
AB  - Human leukocyte antigen (HLA) class II molecule is an integral component of the
      immune response on which the majority of host genetic studies have concentrated.
      Many different HLA-II alleles have been demonstrated to play roles in HBV
      infection. PCR-SSOP methods were applied to determine the HLA-DRB1 genotypes of
      769 unrelated healthy individuals from Han Chinese of Northeast China. The
      frequencies of HLA-DRB1*09 in hepatitis B virus (HBV)-infected subjects were
      higher compared to those in the control group. Frequencies of HLA-DRB1*04 and *13
      in the HBV-infected group were significantly lower compared to those in the
      healthy control group. Frequencies of HLA-DRB1*12 in the cirrhosis and liver
      cancer groups were significantly higher than those in the chronic hepatitis B
      (CHB) patients. The frequency of LA-DRB1*03 in the CHB patient group was
      significantly higher compared to that in the asymptomatic hepatitis B carrier
      patients. The above results suggest that the host HLA-II gene is an important
      factor in the determination of the outcome of HBV infection.

PMID- 22367482
TI  - Reduced tillering in Basmati rice T-DNA insertional mutant OsTEF1 associates with
      differential expression of stress related genes and transcription factors.
AB  - A T-DNA insertional mutant OsTEF1 of rice gives 60-80% reduced tillering,
      retarded growth of seminal roots, and sensitivity to salt stress compared to wild
      type Basmati 370. The insertion occurred in a gene encoding a transcription
      elongation factor homologous to yeast elf1, on chromosome 2 of rice. Detailed
      transcriptomic profiling of OsTEF1 revealed that mutation in the transcription
      elongation factor differentially regulates the expression of more than 100 genes
      with known function and finely regulates tillering process in rice by inducing
      the expression of cytochrome P450. Along with different transcription factors,
      several stress associated genes were also affected due to a single insertion. In
      silico analysis of the TEF1 protein showed high conservation among different
      organisms. This transcription elongation factor predicted to interact with other
      proteins that directly or indirectly positively regulate tillering in rice.

PMID- 22367483
TI  - Os11Gsk gene from a wild rice, Oryza rufipogon improves yield in rice.
AB  - Chromosomal segments from wild rice species Oryza rufipogon, introgressed into an
      elite indica rice restorer line (KMR3) using molecular markers, resulted in
      significant increase in yield. Here we report the transcriptome analysis of flag
      leaves and fully emerged young panicles of one of the high yielding introgression
      lines IL50-7 in comparison to KMR3. A 66-fold upregulated gene Os11Gsk, which
      showed no transcript in KMR3 was highly expressed in O. rufipogon and IL50-7. A 5
      kb genomic region including Os11Gsk and its flanking regions could be PCR
      amplified only from IL50-7, O. rufipogon, japonica varieties of rice-Nipponbare
      and Kitaake but not from the indica varieties, KMR3 and Taichung Native-1. Three
      sister lines of IL50-7 yielding higher than KMR3 showed presence of Os11Gsk,
      whereas the gene was absent in three other ILs from the same cross having lower
      yield than KMR3, indicating an association of the presence of Os11Gsk with high
      yield. Southern analysis showed additional bands in the genomic DNA of O.
      rufipogon and IL50-7 with Os11Gsk probe. Genomic sequence analysis of ten highly
      co-expressed differentially regulated genes revealed that two upregulated genes
      in IL50-7 were derived from O. rufipogon and most of the downregulated genes were
      either from KMR3 or common to KMR3, IL50-7, and O. rufipogon. Thus, we show that
      Os11Gsk is a wild rice-derived gene introduced in KMR3 background and increases
      yield either by regulating expression of functional genes sharing homology with
      it or by causing epigenetic modifications in the introgression line.

PMID- 22367484
TI  - Identification of an miRNA candidate reflects the possible significance of
      transcribed microsatellites in the hairpin precursors of black pepper.
AB  - Plant miRNAs (18-24nt) are generated by the RNase III-type Dicer endonuclease
      from the endogenous hairpin precursors ('pre-miRNAs') with significant regulatory
      functions. The transcribed regions display a higher frequency of microsatellites,
      when compared to other regions of the genomic DNA. Simple sequence repeats (SSRs)
      resulting from replication slippage occurring in transcripts affect the
      expression of genes. The available experimental evidence for the incidence of
      SSRs in the miRNA precursors is limited. Considering the potential significance
      of SSRs in the miRNA genes, we carried out a preliminary analysis to verify the
      presence of SSRs in the pri-miRNAs of black pepper (Piper nigrum L.). We isolated
      a (CT) dinucleotide SSR bearing transcript using SMART strategy. The transcript
      was predicted to be a 'pri-miRNA candidate' with Dicer sites based on miRNA
      prediction tools and MFOLD structural predictions. The presence of this 'miRNA
      candidate' was confirmed by real-time TaqMan assays. The upstream sequence of the
      'miRNA candidate' by genome walking when subjected to PlantCARE showed the
      presence of certain promoter elements, and the deduced amino acid showed
      significant similarity with NAP1 gene, which affects the transcription of many
      genes. Moreover the hairpin-like precursor overlapped the neighbouring NAP1 gene.
      In silico analysis revealed distinct putative functions for the 'miRNA
      candidate', of which majority were related to growth. Hence, we assume that this
      'miRNA candidate' may get activated during transcription of NAP gene, thereby
      regulating the expression of many genes involved in developmental processes.

PMID- 22367485
TI  - Quality of life and autonomy in emerging adults with early-onset neuromuscular
      disorders.
AB  - Emerging adulthood is an important period in the development of one's identity
      and autonomy. The ways in which identity and autonomy are viewed by emerging
      adults and how they impact quality of life (QoL) in individuals with early-onset
      neuromuscular conditions is not yet known. This study focused on understanding
      and exploring relationships between self-perceptions of emerging adulthood,
      autonomy, and QoL. Five previously validated measures were incorporated into an
      online survey and distributed to young adults with early-onset neuromuscular
      conditions and unaffected controls. Topics explored included individuals' views
      regarding their overall QoL, disease-specific QoL, components of emerging
      adulthood, and autonomy. We found that a sense of higher disease impact was
      associated with a lower Overall General QoL. Additionally, perceptions of key
      autonomy factors "negativity" and "instability" were uniquely associated with
      Overall General QoL in the case group as compared to controls, whereas
      "attitudinal autonomy" (attaining the ability to plan and follow through with
      goals) was important to this age group regardless of health status. The specific
      factors of emerging adulthood and autonomy that were significantly correlated
      with Overall General QoL can be used for developing targeted counseling and
      interventions to improve QoL for individuals and their families.

PMID- 22367486
TI  - The yellow catfish, Pelteobagrus fulvidraco (Siluriformes) metallothionein cDNA:
      molecular cloning and transcript expression level in response to exposure to the
      heavy metals Cd, Cu, and Zn.
AB  - Metallothionein (MT) has been used extensively as a potential molecular biomarker
      to detect heavy metal pollution in aquatic organisms. In order to investigate the
      modulation effect of heavy metals and to establish suitable biomarkers for the
      monitoring of heavy metal pollution, Pelteobagrus fulvidraco metallothionein gene
      was characterized as the first report in the family Bagridae. Pf-MT transcript
      was detected at high levels in liver, gonad, kidney, and brain compared to other
      tissues. A time-course study in response to waterborne Cd (5 ppm) revealed that a
      significant increase in the Pf-MT transcript abundance was observed at 6 h in
      gill, kidney, and liver. These elevated levels were kept for 96 h, implying that
      Cd distributed fast into different organs and was involved in the tissue-specific
      induction pattern. We observed a significant Pf-MT transcript increase in liver
      tissues at 48 h, followed by gill at 12 h and intestine at 48 h after Cd
      exposure. This indicates hepatic MT expression as a potential biomarker of acute
      Cd exposure in this species. Cd-binding ability of recombinant Pf-MT protein
      provided evidence for sensitivity to Cd and other heavy metal exposure. In the
      case of Zn exposure (1 ppm), a significant increase in Pf-MT transcript abundance
      was observed at 12 h, and a peak induction level reaching sixfold at 24 h was
      kept until 48 h, showing similar transcript induction patterns with Cd. A high
      level of Pf-MT mRNA after exposure to Cu (1 ppm) was observed at 12 h that
      gradually increased until 96 h with a 12-fold induction, revealing a long-lasting
      induction and somewhat dissimilar pattern compared to other metals in liver. Our
      results demonstrate that Pf-MT can be induced by heavy metals in a tissue
      specific and metal-specific manner and plays probably a conserved role in metal
      detoxification. This study provides new information on P. fulvidraco
      metallothionein gene for the use of biomarkers indicating metal pollution in
      fish.

PMID- 22367488
TI  - Selective recognition of sulfate ions by tripodal cyclic peptides functionalised
      with (thio)urea binding sites.
AB  - A tripodal urea and tripodal thiourea with the same cyclic peptide core have been
      synthesised and their anion binding ability investigated. In CDCl(3), the
      tripodal urea self-associates whereas the thiourea does not. Neither compound
      shows self-association in the more polar 10% v/v DMSO-d(6)/CDCl(3). Both
      compounds bind strongly and selectively to sulfate ions in CDCl(3) and 10% v/v
      DMSO-d(6)/CDCl(3). This selectivity is attributed to a unique binding mode for
      sulfate, in which this tetrahedral anion forms nine hydrogen bonds to the
      receptors, with three of these coming from the amide protons of the cyclic
      peptide.

PMID- 22367487
TI  - Methyl donors potentiates growth, metabolic status and neurotransmitter enzyme in
      Labeo rohita fingerlings exposed to endosulfan and temperature.
AB  - A 2-month preliminary study was conducted to delineate the effect of dietary
      methyl donors (choline, betaine, and lecithin) on the growth performance and
      metabolic status of Labeo rohita fingerlings subjected to endosulfan alone and in
      combination with elevated temperature. Four iso-caloric and iso-nitrogenous diets
      viz. basal diet, betaine-supplemented diet, choline-supplemented diet and
      lecithin-supplemented diet were prepared and fed to the different experimental
      groups throughout the experimental period as per the design. Two hundred and
      seventy fingerlings (average weight 7.95 +/- 0.04 g) were randomly distributed in
      six treatment groups each having three replicates. The experimental groups were
      as follows: fish subjected to normal water (without endosulfan) and fed with
      control diet (control group T(0)), fish subjected to endosulfan-treated water and
      fed with control diet (T(1)), fish subjected to concurrent exposure of endosulfan
      and elevated temperature and fed with control diet (T(2)), fish subjected to
      endosulfan and elevated temperature and fed with choline-supplemented diet
      (T(3)), fish subjected to endosulfan and temperature and fed with betaine
      supplemented feed (T(4)), and fish subjected to endosulfan and temperature and
      fed with lecithin-supplemented feed (T(5)). The result shows that in both the
      groups, that is, endosulfan exposed and concurrent exposure to endosulfan and
      elevated temperature group of L. rohita the growth performance like percentage
      weight gain, feed conversion ratio and specific growth rates were significantly
      different (P < 0.01) when fed with supplemented diet compared with control fed
      group. The liver LDH and MDH activity were significantly lower in lecithin,
      betaine, and choline fed groups. The muscle AST as well as G6PDH, AST, and ALT
      did not vary but liver ALT, gill and liver ATPase, intestine ALP, muscle and
      liver glycogen varied significantly with dietary supplementation. The liver and
      gill glutathione-S-transferase (GST) activities were significantly lower in
      methyl donors-supplemented groups and brain AChE activity showed lower inhibition
      in supplemented groups in both endosulfan alone and concurrently exposed
      endosulfan and temperature groups. The result obtained in this study concludes
      that inclusion of methyl donors, particularly lecithin and betaine in feed as
      nutritional supplements have potential to improve growth and stress mitigating
      effect in L. rohita fingerlings.

PMID- 22367489
TI  - Effect of the rd1 mutation on motor performance in R6/2 and wild type mice.
AB  - Homozygosis for the rd1 mutation in the Pbe6b gene results in the loss of the rod
      b-subunit of the cyclic GMP phosphodiesterase and, eventually, of all rod and
      cone photoreceptors. The R6/2 mouse line is a widely used model of Huntington's
      disorder (HD). The original line was made available on a mixed background
      obtained by crossing, via ovarian transplant, female R6/2 (on a B6CBA mixed
      background) with male B6CBAF1/J mice. As the CBA/J strain used in the US is
      homozygous for the rd1 mutation and the breeding scheme does not ensure
      heterozygosis for the mutation, a significant percentage of the offspring on this
      mixed background is expected to be homozygous for the rd1 mutation. We
      investigate here the effect of rd1 homozygosis on motor function and examined the
      effects of the mutation on the R6/2 phenotype. Homozygosis for the rd1 mutation
      resulted in increased activity in the open field test and reduced rotarod test
      performance. In addition, rd1 mutation absence or heterozygosis reduced the
      differences between the R6/2 and the WT mice. Our recommendation for the
      neurodegeneration field, and for all mouse studies in general, is to carefully
      control homozygosis for retinal degeneration mutation, even when using tests of
      motor function.

PMID- 22367490
TI  - Collaborative practice through simulations in a multiuser virtual environment.

PMID- 22367492
TI  - Nurses called upon as advocates for patient empowerment through technology.

PMID- 22367494
TI  - Co-remediation of cadmium-polluted soil using stainless steel slag and ammonium
      humate.
AB  - INTRODUCTION AND METHODS: This study investigated the remediation of cadmium
      polluted soil using a combination of stainless steel slag and ammonium humate.
      These remedial agents were added to an artificially polluted garden soil to
      inhabit cadmium toxicity in soil by changing the physical and chemical properties
      of soil in a pot experiment. RESULTS AND CONCLUSIONS: The results showed that the
      co-application of ammonium humate and stainless steel slag significantly
      decreased the total and available soil cadmium concentrations, with maximum
      decreases of 16.30% and 58.04%, respectively. The co-application of an adequate
      dose of these remedial agents can significantly increase soil pH. The soil
      organic matter and cation exchange capacity, as well as the amount of soil
      aggregates, were also significantly increased by the addition ammonium humate,
      but not stainless steel slag.

PMID- 22367495
TI  - Arsenic uptake and speciation and the effects of phosphate nutrition in
      hydroponically grown kikuyu grass (Pennisetum clandestinum Hochst).
AB  - BACKGROUND: This work focuses on the accumulation and mobility properties of
      arsenic (As) and the effects of phosphate (P) on its movement in Pennisetum
      clandestinum Hochst (kikuyu grass), grown hydroponically under increasing
      arsenate (As(V)) concentrations. The uptake of both ions and the relative
      kinetics show that phosphate is an efficient competitive inhibitor of As(V)
      uptake. The P/As uptake rate ratios in roots indicate that P is taken up
      preferentially by P/As transporters. An arsenite (As(III)) efflux from roots was
      also found, but this decreased when the arsenate concentration in the solution
      exceeded 5 MUM. METHODS: Increases in both arsenite and arsenate concentrations
      in roots were observed when the arsenate concentration in the solution was
      increased, and the highest accumulation of As(III) in roots was found when plants
      were grown at 5 MUM As(V). The low ratios of As accumulated in shoots compared to
      roots suggest limited mobility of the metalloid within Kikuyu plants. RESULTS:
      The results indicate that arsenic resistance in kikuyu grass in conditions of
      moderate exposure is mainly dependent on the following factors: 1) phosphate
      nutrition: P is an efficient competitive inhibitor of As(V) uptake because of the
      higher selectivity of membrane transporters with respect to phosphate rather than
      arsenate; and 2) a detoxification mechanism including a reduction in both
      arsenate and arsenite root efflux. CONCLUSIONS: The As tolerance strategy of
      Kikuyu limits arsenate uptake and As translocation from roots to shoots;
      therefore, this plant cannot be considered a viable candidate for use in the
      phytoextraction of arsenic from contaminated soils or water.

PMID- 22367496
TI  - Improvement of biodegradability of PVA-containing wastewater by ionizing
      radiation pretreatment.
AB  - BACKGROUND: Polyvinyl alcohol (PVA) has been widely used as sizing agents in
      textile and manufacturing industry, and it is a refractory compound with low
      biodegradability. OBJECTIVE: The objective of this paper was to treat the PVA
      containing wastewater using gamma irradiation as a pretreatment strategy to
      improve its biodegradability and to determine the roles of different kinds of
      radical species played during pretreatment. METHODS: Gamma radiation was carried
      out in a (60)Cobalt source station, PVA concentration was analyzed by using a
      visible spectrophotometer and specific oxygen uptake rate (SOUR, milligram of
      O(2) per gram of mixed liquor volatile suspended solids (MLVSS) per hour) was
      measured by a microrespirometer. RESULTS: The results showed that the
      biodegradability of PVA-containing wastewater with low initial concentration
      (e.g., 327.8 mg/l) could be improved greatly with increasing irradiation dose.
      However, PVA gel formation was observed at higher initial PVA concentration
      (e.g., 3,341.6 mg/l) and higher irradiation dose, which inhibited PVA degradation
      by aerobic microorganisms. However, the formed gel could be separated by
      microfiltration, which led to more than 90% total organic carbon (TOC) removal.
      CONCLUSION: Ionizing radiation could be used as a pretreatment technology for PVA
      containing wastewater, and its combination with biological process is feasible.

PMID- 22367497
TI  - Zinc induces caspase-dependent mitochondrial pathway of the programmed cell death
      in haemocytes of Drosophila melanogaster.
AB  - Zinc is an essential trace element in cells. However, its high level in cytoplasm
      promotes activation of stress signaling pathways and may lead to cell death. In
      the present study we used Drosophila melanogaster blood cells (haemocytes),
      obtained from the third instar larvae, to study the effects of high
      concentrations of Zn(2+) on programmed cell death (PCD). We analyzed the activity
      of caspases, the level of caspase inhibitor protein DIAP1 and metallothioneins,
      as well as calcium concentrations and activity of mitochondria in haemocytes
      exposed to 0.35 and 1.7 mM concentrations of Zn. The obtained results showed that
      rapid increase of [Zn(2+)]( i ) in the cytoplasm up-regulates metallothionein
      MtnB but not MtnA gene expression in cells treated with Zn(2+) in both
      concentrations. Excess of Zn(2+) also induced activation of the initiator caspase
      Dronc, associated with the mitochondrial pathway of PCD, and the effector caspase
      DrICE. In turn, the activity of receptor-regulated Dredd caspase was not changed.
      The level of DIAP1 decreased significantly in haemocytes in the presence of high
      Zn(2+) concentration in comparison to untreated cells. Moreover, mitochondrial
      membrane potential was significantly decreased after exposure to Zn ions. These
      results indicate that high concentration of Zn(2+) in the cytoplasm of haemocytes
      induces PCD via a mitochondrial pathway and that caspases play a pivotal role in
      this process.

PMID- 22367498
TI  - Bioaccumulation of polybrominated diphenyl ethers by the freshwater benthic
      amphipod Gammarus pulex.
AB  - This study reports on the relationship between polybrominated diphenyl ether
      (PBDE) levels in water, sediment, and the benthic macroinvertebrate Gammarus
      pulex, which plays a major ecological role in freshwater ecosystems. Samples were
      taken in a periurban watershed (near Paris, France), and PBDEs were
      systematically detected in sediment (<=727 ng g(-1) OC) and G. pulex (<=264 ng g(
      1) lipids). PBDEs were also occasionally detected in the water column at low
      levels (? PBDEs < 1.5 ng L(-1)). The log values of bioaccumulation factors were
      in the range 7.8 +/- 0.1-8.3 +/- 0.4 L kg(-1) for tetra- and penta-BDEs, which
      were the only ones quantified in the dissolved phase of river water. Meanwhile,
      levels of individual tri- to hepta-PBDE congeners in G. pulex generally
      positively correlated with sediment levels, suggesting an equilibrium situation.
      Biota-to-sediment accumulation factors (BSAFs) of tri-hepta BDEs were congener
      specific and were in the range 0.5 +/- 0.3-2.6 +/- 1.2. For several PBDEs, BSAF
      values deviated from the expected range, likely because of in vivo metabolism.

PMID- 22367499
TI  - Human immunodeficiency virus testing practices among buprenorphine-prescribing
      physicians.
AB  - BACKGROUND: Despite the Centers for Disease Control and Prevention
      recommendations for annual HIV testing of at-risk populations, including those
      with substance use disorders, there are no data on the human immunodeficiency
      virus (HIV) testing practices of buprenorphine-prescribing physicians. OBJECTIVE:
      To describe HIV testing practices among buprenorphine-prescribing physicians.
      METHODS: We conducted a cross-sectional survey of physicians enrolled in a
      national system to support buprenorphine prescribing between July and August
      2008. The electronic survey included questions on demographics; clinical training
      and experience; clinical practice; patient characteristics; and physician
      screening practices, including HIV testing. RESULTS: Only 46% of 382 respondent
      physicians conducted HIV testing. On univariate analysis, physicians who
      conducted HIV testing were more likely to report addiction specialty training
      (33% vs 19%, P = 0.001), practicing in addiction settings (28% vs 16%, P =
      0.006), and having treated more than 50 patients with buprenorphine (50% vs 31%,
      P < 0.0001) than those who did not. Compared with physicians who did not conduct
      HIV testing, physicians who conducted HIV testing had a lower proportion of
      buprenorphine patients who were white (75% vs 82%, P = 0.01) or dependent upon
      prescription opioids (57% vs 70%, P < 0.0001). In multivariate analysis,
      physicians who conducted HIV testing were more likely to have treated more than
      50 patients with buprenorphine (odds ratio = 1.777, 95% CI 1.011-3.124) and had
      fewer patients dependent upon prescription opioids (odds ratio = 0.986 95% CI
      0.975-0.998) than physicians who did not. CONCLUSIONS: Interventions to increase
      HIV testing among physicians prescribing buprenorphine are needed.

PMID- 22367500
TI  - Genetic characterization of influenza A virus subtype H12N1 isolated from a
      watercock and lesser whistling ducks in Thailand.
AB  - Monitoring of influenza A virus (IAV) was conducted in wild bird species in
      central Thailand. Four IAV subtype H12N1 strains were isolated from a watercock
      (order Gruiformes, family Rallidae) (n = 1) and lesser whistling ducks (order
      Anseriformes, family Anatidae) (n = 3). All H12N1 viruses were characterized by
      whole-genome sequencing. Phylogenetic analysis of all eight genes of the Thai
      H12N1 viruses indicated that they are most closely related to the Eurasian
      strains. Analysis of the HA gene revealed the strains to be of low pathogenicity.
      This study is the first to report the circulation of IAV subtype H12N1 in
      Thailand and to describe the genetic characteristics of H12N1 in Eurasia.
      Moreover, the genetic information obtained on H12N1 has contributed a new
      Eurasian strain of H12N1 to the GenBank database.

PMID- 22367501
TI  - A large outbreak of enteritis in goat flocks in Marmara, Turkey, by G8P[1] group
      A rotaviruses.
AB  - Group A rotaviruses are regarded as major enteric pathogens of large ruminants,
      while their impact on the health of small ruminants is not well documented. We
      report the detection of group A rotavirus from a large outbreak of enteritis that
      occurred in two goat flocks in the town of Kirklareli, Marmara Region, Turkey, in
      2007. The disease was observed in young kids, with high morbidity and mortality
      rates, but not in adult animals. Rotavirus antigen was detected in the stools of
      the examined animals, and rotaviruses were isolated in MA104 cells. Upon
      sequencing of the VP4, VP6, VP7 and NSP4 genes, the strain (RVA/goat
      tc/TUR/Kirklareli/2007/G8P[1]) was characterized as G8P[1], with E2 NSP4 and VP6
      I2 genotype. These findings indicate that group A rotavirus should be included in
      the diagnostic algorithms for enteric disease in small ruminants.

PMID- 22367502
TI  - Affect balance style, experimental pain sensitivity, and pain-related responses.
AB  - OBJECTIVES: Affect is neurobiologically based, influences emotions, contributes
      to temperamental characteristics, and can be evaluated from both state and trait
      perspectives. Associations between state-related positive affect (PA), negative
      affect (NA), and chronic pain have been investigated. However, little is known
      about the relationship between trait affect patterns and pain-related
      experiences. Affect balance style (ABS) provides a framework to assess the
      combined contribution of trait PA and NA. Psychological factors and experimental
      pain sensitivity are indicated as predictors of chronic pain onset. The current
      study investigated the relationship between ABS, pain sensitivity, and pain
      related measures in healthy adults. METHODS: Participants (n=372) completed
      quantitative sensory testing, pain-related questionnaires, and the Positive and
      Negative Affect Scale. ABS groups were categorized as Healthy (high PA, low NA),
      Low (low PA, low NA), Depressive (low PA, high NA), and Reactive (high PA, high
      NA). Z-scores were computed for 3 experimental pain measures: ischemic, pressure,
      and heat. RESULTS: ABS groups significantly differed on ischemic pain sensitivity
      and pain-related measures. Specifically, the Healthy group demonstrated lower
      ischemic pain sensitivity compared with the Reactive group (P=0.02); the
      Depressive and Reactive groups endorsed higher somatic symptoms compared with the
      Healthy group (P<0.02); the Low and Depressive groups reported more physical
      stimuli sensitivity than the Healthy group (P<0.02); and the Reactive group
      indicated more passive coping strategies then the Low and Healthy groups
      (P=0.001). DISCUSSION: Findings from the study suggest that among healthy adults,
      trait affect patterns are associated with ischemic experimental pain sensitivity
      and other pain-related measures.

PMID- 22367503
TI  - Cannabinergic pain medicine: a concise clinical primer and survey of randomized
      controlled trial results.
AB  - OBJECTIVES: This article attempts to cover pragmatic clinical considerations
      involved in the use of cannabinergic medicines in pain practice, including
      geographical and historical considerations, pharmacokinetics, pharmacodynamics,
      adverse effects, drug interactions, indications, and contraindications. Topics
      include molecular considerations such as the 10-fold greater abundance of
      cannabinoid type 1 receptors compared to u-opioid receptors in the central
      nervous system and anatomic distributions of cannabinoid receptors in pain
      circuits. METHODS: The article uses a narrative review methodology drawing from
      authoritative textbooks and journals of cannabinoid medicine, Food and Drug
      Administration-approved cannabinoid drug labels, and current and historical pain
      medicine literature to address core clinical considerations. To survey the
      current evidence base for pain management with cannabinergic medicines, a
      targeted PubMed search was performed to survey the percentage of positive and
      negative published randomized-controlled trial (RCT) results with this class of
      pain medicines, using appropriate search limit parameters and the keyword search
      string "cannabinoid OR cannabis-based AND pain." RESULTS: Of the 56 hits
      generated, 38 published RCTs met the survey criteria. Of these, 71% (27)
      concluded that cannabinoids had empirically demonstrable and statistically
      significant pain-relieving effects, whereas 29% (11) did not. DISCUSSION:
      Cannabis and other cannabinergic medicines' efficacies for relieving pain have
      been studied in RCTs, most of which have demonstrated a beneficial effect for
      this indication, although most trials are short-term. Adverse effects are
      generally nonserious and well tolerated. Incorporating cannabinergic medicine
      topics into pain medicine education seems warranted and continuing clinical
      research and empiric treatment trials are appropriate.

PMID- 22367504
TI  - Regulation of phosphatase and tensin homolog on chromosome 10 in response to
      hypoxia.
AB  - Phosphatase and tensin homolog on chromosome 10 (PTEN) is downregulated during
      hypertrophic and cancerous cell growth, leading to activation of the prosurvival
      Akt pathway. However, PTEN regulation in cardiac myocytes upon exposure to
      hypoxia remains unclear. We explored the role of PTEN in response to
      hypoxia/ischemia in the myocardium. We validated that PTEN is a transcriptional
      target of activating transcription factor 2 (ATF-2) and is positively regulated
      via a p38/ATF-2 signaling pathway. Accordingly, hypoxia-induced upregulation of
      phosphorylation of ATF-2 and PTEN were reversed by a dominant negative mutant
      p38. Inhibition of PTEN in cardiomyocytes attenuated hypoxia-induced cell death
      and apoptosis. Cardiac-specific knockout of PTEN resulted in increased
      phosphorylation of Akt and forkhead box O 1 (forkhead transcription factors),
      limited infarct size in animals exposed to ischemia-reperfusion injury, and
      ameliorated deterioration of left ventricular function and remodeling following
      permanent coronary artery occlusion. In addition, the activation of Bim, FASL,
      and caspase was coupled with PTEN activation, all of which were attenuated by
      PTEN inhibition. In conclusion, cardiomyocyte-specific conditional PTEN deletion
      limited myocardial infarct size in an in vivo model of ischemia-reperfusion
      injury and attenuated adverse remodeling in a model of chronic permanent coronary
      artery ligation.

PMID- 22367505
TI  - Cardioprotection of electroacupuncture against myocardial ischemia-reperfusion
      injury by modulation of cardiac norepinephrine release.
AB  - Augmentation of cardiac sympathetic tone during myocardial ischemia has been
      shown to increase myocardial O(2) demand and infarct size as well as induce
      arrhythmias. We have previously demonstrated that electroacupuncture (EA)
      inhibits the visceral sympathoexcitatory cardiovascular reflex. The purpose of
      this study was to determine the effects of EA on left ventricular (LV) function,
      O(2) demand, infarct size, arrhythmogenesis, and in vivo cardiac norepinephrine
      (NE) release in a myocardial ischemia-reperfusion model. Anesthetized rabbits (n
      = 36) underwent 30 min of left anterior descending coronary artery occlusion
      followed by 90 min of reperfusion. We evaluated myocardial O(2) demand, infarct
      size, ventricular arrhythmias, and myocardial NE release using microdialysis
      under the following experimental conditions: 1) untreated, 2) EA at P5-6
      acupoints, 3) sham acupuncture, 4) EA with pretreatment with naloxone (a
      nonselective opioid receptor antagonist), 5) EA with pretreatment with
      chelerythrine (a nonselective PKC inhibitor), and 6) EA with pretreatment with
      both naloxone and chelerythrine. Compared with the untreated and sham acupuncture
      groups, EA resulted in decreased O(2) demand, myocardial NE concentration, and
      infarct size. Furthermore, the degree of ST segment elevation and severity of LV
      dysfunction and ventricular arrhythmias were all significantly decreased (P <
      0.05). The cardioprotective effects of EA were partially blocked by pretreatment
      with naloxone or chelerythrine alone and completely blocked by pretreatment with
      both naloxone and chelerythrine. These results suggest that the cardioprotective
      effects of EA against myocardial ischemia-reperfusion are mediated through
      inhibition of the cardiac sympathetic nervous system as well as opioid and PKC
      dependent pathways.

PMID- 22367506
TI  - Myocardial infarction impairs renal function, induces renal interstitial
      fibrosis, and increases renal KIM-1 expression: implications for cardiorenal
      syndrome.
AB  - Progressive decline in renal function coexists with myocardial infarction (MI);
      however, little is known about its pathophysiology. This study aimed to
      systematically identify post-MI renal changes (functional, histological, and
      molecular) over time in a rat MI model and examine potential mechanisms that may
      underlie these changes. Rats were randomized into three groups: nonoperated,
      sham, and MI. Cardiac and renal function was assessed before death at 1, 4, 8,
      12, and 16 wk with tissues collected for histological, protein, and gene studies.
      Tail-cuff blood pressure was lower in MI than sham and nonoperated animals only
      at 1 wk (P < 0.05). Systolic function was reduced (P < 0.0001) while heart/body
      weight and left ventricle/body weight were significantly greater in MI animals at
      all time points. Glomerular filtration rate decreased following MI at 1 and 4 wk
      (P < 0.05) but not at 8 and 12 wk and then deteriorated further at 16 wk (P =
      0.052). Increased IL-6 gene and transforming growth factor (TGF)-beta protein
      expression as well as macrophage infiltration in kidney cortex was detected at 1
      wk (P < 0.05). Renal cortical interstitial fibrosis was significantly greater in
      MI animals from 4 wk, while TGF-beta bioactivity (phospho-Smad2) was upregulated
      at all time points. The degree of fibrosis increased and was maximal at 16 wk. In
      addition, kidney injury molecule-1-positive staining in the tubules was more
      prominent in MI animals, maximal at 1 wk. In conclusion, renal impairment occurs
      early post-MI and is associated with hemodynamic and structural changes in the
      kidney possibly via activation of the Smad2 signaling pathway.

PMID- 22367507
TI  - Role of the human erythrocyte in generation and storage of asymmetric
      dimethylarginine.
AB  - Proteolytic activity in whole blood may lead to release of the endogenous nitric
      oxide synthase inhibitor asymmetric dimethylarginine (ADMA). We investigated the
      role of the human erythrocyte in storage and generation of ADMA in healthy
      controls (n = 36) and critically ill patients (n = 38). Both free and total (sum
      of free and protein-incorporated) ADMA were measured. Upon incubation of intact
      erythrocytes with extracellular ADMA (0 to 40 MUmol/l), equilibrium between intra
      and extracellular ADMA was reached within 3 h. Compared with controls, patients
      had significantly higher basal concentrations of ADMA in plasma (0.88 +/- 0.75
      vs. 0.41 +/- 0.07 MUmol/l) and erythrocytes (1.28 +/- 0.55 vs. 0.57 +/- 0.14
      MUmol/l). Intracellular and plasma ADMA were significantly correlated in the
      patient group only (r = 0.834). Upon lysis, followed by incubation at 37 degrees
      C for 2 h, free ADMA increased sevenfold (to 8.60 +/- 3.61 MUmol/l in patients
      and 3.90 +/- 0.78 MUmol/l in controls). In lysates of controls, free ADMA
      increased further to 9.85 +/- 1.35 MUmol/l after 18 h. Total ADMA was 15.43 +/-
      2.44 MUmol/l and did not change during incubation. The increase of free ADMA
      during incubation corresponded to substantial release of ADMA from the
      erythrocytic protein-incorporated pool (21.9 +/- 4.6% at 2 h and 60.8 +/- 7.6% at
      18 h). ADMA was released from proteins other than hemoglobin, which only occurred
      after complete lysis and was blocked by combined inhibition of proteasomal and
      protease activity. Neither intact nor lysed erythrocytes mediated degradation of
      free ADMA. We conclude that intact erythrocytes play an important role in storage
      of ADMA, whereas upon erythrocyte lysis large amounts of free ADMA are generated
      by proteolysis of methylated proteins, which may affect plasma levels in
      hemolysis-associated diseases.

PMID- 22367508
TI  - Effect of heat stress on cardiac output and systemic vascular conductance during
      simulated hemorrhage to presyncope in young men.
AB  - During moderate actual or simulated hemorrhage, as cardiac output decreases,
      reductions in systemic vascular conductance (SVC) maintain mean arterial pressure
      (MAP). Heat stress, however, compromises the control of MAP during simulated
      hemorrhage, and it remains unknown whether this response is due to a persistently
      high SVC and/or a low cardiac output. This study tested the hypothesis that an
      inadequate decrease in SVC is the primary contributing mechanism by which heat
      stress compromises blood pressure control during simulated hemorrhage. Simulated
      hemorrhage was imposed via lower body negative pressure (LBNP) to presyncope in
      11 passively heat-stressed subjects (increase core temperature: 1.2 +/- 0.2
      degrees C; means +/- SD). Cardiac output was measured via thermodilution, and SVC
      was calculated while subjects were normothermic, heat stressed, and throughout
      subsequent LBNP. MAP was not changed by heat stress but was reduced to 45 +/- 12
      mmHg at the termination of LBNP. Heat stress increased cardiac output from 7.1 +/
      1.1 to 11.7 +/- 2.2 l/min (P < 0.001) and increased SVC from 0.094 +/- 0.018 to
      0.163 +/- 0.032 l.min(-1).mmHg(-1) (P < 0.001). Although cardiac output at the
      onset of syncopal symptoms was 37 +/- 16% lower relative to pre-LBNP, presyncope
      cardiac output (7.3 +/- 2.0 l/min) was not different than normothermic values (P
      = 0.46). SVC did not change throughout LBNP (P > 0.05) and at presyncope was
      0.168 +/- 0.044 l.min(-1).mmHg(-1). These data indicate that in humans a cardiac
      output adequate to maintain MAP while normothermic is no longer adequate during a
      heat-stressed-simulated hemorrhage. The absence of a decrease in SVC at a time of
      profound reductions in MAP suggests that inadequate control of vascular
      conductance is a primary mechanism compromising blood pressure control during
      these conditions.

PMID- 22367509
TI  - STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil
      in human colorectal cancer cells.
AB  - Signal transducers and activators of transcription 5 (STAT5) has been shown to be
      involved in a variety of cellular processes, including survival, proliferation,
      invasion, angiogenesis and immune evasion and is frequently overexpressed in
      human solid tumors and blood malignancies. The aim of this study was to
      investigate the role of STAT5a in colorectal cancer (CRC) progression. We
      inhibited the expression of STAT5a using lentivirus-mediated artificial microRNA
      (miRNA) interference in vitro and investigated the viability of CRC cells by CCK
      8 assay. We observed the cell viability after treatment with cisplatin (CDDP) or
      5-fluorouracil (5-Fu) by CCK-8 assay, and the apoptosis induced by chemotherapy
      using flow cytometric analysis and Annexin V RFP staining assay. We inhibited the
      mRNA expression by 54% and the protein expression by 60% of STAT5 by RNA
      interference targeting STAT5a. Cell viability assays showed that inhibition of
      STAT5a did not affect the viability of SW1116 cells. However, we found that
      inhibition of STAT5a restored the sensitivity of SW1116 cells to CDDP and 5-Fu.
      In additional experiments, we found that inhibition of STAT5a significantly
      promoted CRC cell apoptosis by CDDP and 5-Fu. In the present study, we found that
      inhibition of STAT5a promotes apoptosis of CRC cells induced by chemotherapy
      drugs, such as CDDP or 5-Fu. These results suggest that inhibition of STAT5a may
      serve as a potential new target for CRC treatment.

PMID- 22367510
TI  - Analysis of a nanocrystalline polymer dispersion of ebselen using solid-state
      NMR, Raman microscopy, and powder X-ray diffraction.
AB  - PURPOSE: Nanocrystalline drug-polymer dispersions are of significant interest in
      pharmaceutical delivery. The purpose of this work is to demonstrate the
      applicability of methods based on two-dimensional (2D) and multinuclear solid
      state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen
      with polyvinylpyrrolidone-vinyl acetate (PVP-VA), after initial characterization
      with other techniques. METHODS: A nanocrystalline dispersion of ebselen with PVP
      VA was prepared and characterized by powder X-ray diffraction (PXRD), confocal
      Raman microscopy and mapping, and differential scanning calorimetry (DSC), and
      then subjected to detailed 1D and 2D SSNMR analysis involving 1H, 13C, and 77Se
      isotopes and 1H spin diffusion. RESULTS: PXRD was used to show that dispersion
      contains nanocrystalline ebselen in the 35-60 nm size range. Confocal Raman
      microscopy and spectral mapping were able to detect regions where short-range
      interactions may occur between ebselen and PVP-VA. Spin diffusion effects were
      analyzed using 2D SSNMR experiments and are able to directly detect interactions
      between ebselen and the surrounding PVP-VA. CONCLUSIONS: The methods used here,
      particularly the 2D SSNMR methods based on spin diffusion, provided detailed
      structural information about a nanocrystalline polymer dispersion of ebselen, and
      should be useful in other studies of these types of materials.

PMID- 22367511
TI  - Recent advances in treatment of advanced urothelial carcinoma.
AB  - GC (cisplatin and gemcitabine) and MVAC (methotrexate, vinblastine, Adriamycin
      [doxorubicin], and cisplatin) have been the standard systemic chemotherapy in
      advanced urothelial carcinoma. These regimens have shown significant response
      rates in this patient population. Nevertheless, disease does recur with most
      patients who unfortunately do succumb to the disease. Research efforts are
      focused in several different areas of therapy, targeted therapy, and
      immunotherapy. Further efforts include those in improving understanding of the
      molecular biology of urothelial carcinoma which may lead development of
      biomarkers that may enhance therapeutic index. This paper reviews recent advances
      in the treatment and ongoing study of molecular biology of urothelial carcinoma.

PMID- 22367512
TI  - Gambling-related harms among adolescents: a population-based study.
AB  - Internationally, and also in Europe, adolescent gambling is increasingly
      recognized as an important public health issue. Most research on adolescent
      gambling, however, is prevalence-focused and population-based studies are scarce.
      Few studies have examined gambling-related harms among adolescents. In a national
      sample, we examined self-experienced harms related to gambling and the
      relationship between reported harms and gambling behavior among Finnish
      adolescents. A national survey of 12-18-year-olds was conducted in Finland in
      2011 (N = 4,566). Main measures were frequency of gambling and gambling-related
      harms reported during the past 6 months. The relationship between reported harms
      and gambling behavior was assessed using logistic regression analysis. Overall,
      44% had gambled during the past 6 months. Of the sample, 12% were frequent
      gamblers (at least weekly) and 32% were occasional gamblers (monthly or less
      often). Compared to occasional gamblers, frequent gamblers were more likely to
      experience harms. The most commonly reported harms among frequent gamblers were
      "felt guilty or shameful due to gambling" (17%) followed by "problems with
      relationships" (13%) and "disruptions of daily rhythm" (10%). In age and gender
      adjusted analysis, daily gamblers were significantly more likely to report all
      different types of harms when compared to other groups. These findings suggest
      that when planning and targeting youth gambling prevention and harm reduction
      strategies the nature and extent to which gambling may contribute to the
      different types of harms are important to consider.

PMID- 22367513
TI  - [Intraoperative 3D C-arm imaging. State of the art].
AB  - Mobile C-arms with the option of 3D imaging like the Iso-C(3D) allow for
      intraoperative 3D visualization of anatomical areas with complex three
      dimensional structures like articular surfaces. In an 8-year period we performed
      1,841 intraoperative control scans following osteosynthesis. Among these patients
      we registered the number of intraoperative adjustments of fracture reduction and
      implant position in correlation to the area of surgery. The majority of
      intraoperative examinations in 1,841 patients was performed in fractures of the
      calcaneus (20.5%) and the upper ankle joint (13.2%). Altogether we improved the
      reduction or the implant position intraoperatively in 21.5%. The majority of
      intraoperative revisions was seen in osteosynthesis of the calcaneus (40.3%), the
      upper ankle joint (30.9%) and fractures of the distal tibia (29%). The rate of
      revisions over the time was very stable. Intraoperative need for revision of
      reduction or implant position is not a rare phenomenon in our experience.
      Intraoperative 3D imaging is a valid tool to recognize and adjust suboptimal
      reduction or implant positioning. Intraoperative 3D imaging can improve the
      quality of osteosynthesis especially in fractures of joints and complex
      anatomical areas.

PMID- 22367514
TI  - [Traumatic dissection of the internal carotid artery following whiplash injury.
      Diagnostic workup and therapy of an often overlooked but potentially dangerous
      additional vascular lesion].
AB  - We report on the case of a 33-year-old male patient who was brought to the
      emergency room of our hospital after suffering a high-energy trauma due to an
      automobile accident. Besides a scaphoid fracture there were no signs of any
      neurological deficits. After several hours without clinical symptoms the patient
      developed dysarthria as the first manifestation of local cerebral ischemia based
      on a traumatic dissection of the internal carotid artery. Under systemic high
      dose heparin therapy, fast and complete remission of all neurological disorders
      could be achieved. In the course of time a dissecting aneurysm developed.
      Temporary anticoagulation with phenprocoumon was started in the meantime and no
      further complications have appeared up to now. Besides presenting this absorbing
      case, this article highlights the diagnostic and therapeutic regime in cases of a
      traumatic dissection of supra-aortal arteries for rapid and adequate management
      of this rare but potentially dangerous complication.

PMID- 22367515
TI  - [Long-term results following denervation of the wrist].
AB  - BACKGROUND: This retrospective study examines long-term follow-up results after
      complete denervation of the wrist. PATIENTS AND METHODS: Between 1994 and 2000 a
      total of 61 complete wrist denervations of 59 patients (median age at operation
      46 years) were performed. In 2009 29 patients with 30 complete wrist denervations
      took part in a follow-up examination after an average of 10 years. The mobility
      of the wrist and the grip force were examined. Pain and satisfaction with the
      operation were determined by means of a visual analogue scale (VAS) (0-100). The
      patients were asked about pain reduction and how long it lasted. Further the DASH
      and the Mayo Wrist Score were evaluated. Radiographs of the denervated wrist were
      performed and the degree of the degenerative osteoarthritis was determined
      according to Knirk and Jupiter. RESULTS: In 7 of the 36 patients examined, a
      partial or total wrist arthrodesis was performed. These patients were excluded
      from the study. Pain was improved in 28 of the 30 denervated wrists examined, in
      22 the improvement lasted until the follow-up examination, whereas in 6 the pain
      increased after a median of 90 months. The median pain intensity was 10 at rest
      and 50 with activity; the satisfaction was 90. The median of the
      extension/flexion was 81% and the grip force 82% in comparison to the opposite
      hand. The DASH Score was 25 and the Mayo Wrist Score 73. CONCLUSION: Complete
      denervation of the wrist according to Wilhelm is a treatment option for the
      chronically painful wrist and can lead to good grip force, mobility, sufficient
      pain reduction and satisfaction in the long term.

PMID- 22367516
TI  - [Pericardial perforation 2.5 years after kyphoplasty. A rare complication after
      cement extravasation].
AB  - Kyphoplasty is an established method in the treatment of osteoporotic spine
      fractures. In 10-15% of cases cement extravasation and leakage into veins occur.
      We report about the rare course of an extravasation. In 2008 an osteoporotic
      compression fracture of L(4) and L(5) in a 62-year-old female patient was treated
      by kyphoplasty. In the treated vertebra filling of an outgoing vein towards the
      proximal right side occurred. Postoperatively the patient was free of complaints
      (VAS preoperative 9/10, postoperative 1/10). In the chest X-ray a small
      asymptomatic filling of a lung vessel on the left side was present. The patient
      arrived as an emergency case 2.5 years later with decompensated heart failure. In
      the chest CT and angiography cement emboli in the lung were seen as well as a
      perforation of the pericardium with beginning tamponade. A thoracotomy was
      performed. Intraoperatively two 4 cm long sharp cement pieces were removed from
      the heart, which had perforated the right ventricle. Leakages were closed by
      suture. The patient survived the operation and was dismissed after 2 weeks of
      intensive care for rehabilitation and from there dismissed home. Six months later
      she had no more problems. When filling vertebra in several levels one must pay
      attention to introducing cement with a thick consistency, otherwise venous emboli
      and lung emboli may occur. These are as a rule asymptomatic, but may result in
      exceptional life-threatening complications.

PMID- 22367517
TI  - [Image-based guidance in shoulder traumatology. Initial clinical experience].
AB  - Computer-assisted systems are used frequently in pelvis and spine surgery but are
      still rare in general trauma and hardly ever used in shoulder surgery. The major
      limitation is the use of rigid markers and the problem of obtaining navigable
      images in the complex shoulder region. The aim of this study was to evaluate the
      use of a new image-based guidance system in shoulder traumatology. The system was
      used to implant a tightrope system in Tossy III lesions of the AC joint (n=7) and
      compared to the conventional method (n=8). Outcome parameters were duration of
      surgery, number of trials for perfect positioning of the guide wire, C-arm shots
      used till K-wire position is accepted, duration of radiation and surgeon's
      comment on usability and benefit. The new system did not shorten the surgical
      procedure significantly (45 vs 49 min, p=0.6) but reduced the average overall
      radiation time from 152 to 90 s (p=0.3). The number of shots to implant the guide
      wire could be reduced significantly from 8 to 5 (p=0.01). The number of trials to
      implant the guide wire was less in the image-guided group compared to the
      conventional group (1 vs 2, p=0.02). For the first time image-based guidance was
      used in shoulder traumatology. The system holds high potential to assist surgeons
      without disturbing the workflow in assuring guide wire positioning, reduce the
      number of dangerous mistrials and reduce the emission of radiation.

PMID- 22367518
TI  - [Modern intraoperative imaging techniques, part II].

PMID- 22367519
TI  - [Post-traumatic bipolar dislocation of the clavicle: is operative treatment
      reasonable?].
AB  - Bipolar dislocation of the clavicle ("floating clavicle") is extremely rare. It
      exists no standardised treatment for this trauma and the treatment is often
      conservative. This is mainly an anterior displacement of the sternoclavicular
      joint (type III according to Allman) and a posterior dislocation of the
      acromioclavicular joint (type IV according to Rockwood).We report on a 60 year
      old male who fell onto the right shoulder. He sustained a 'floating clavicle' and
      had a massive dislocation, impairment of range of motion and pain. Venous
      congestion was observable. We stabilised the dislocated acromioclavicular joint
      with a Balser's plate, the sternoclavicular joint was fixed with PDS cord tension
      band technique around the first rip and the sternum. In addition we resected the
      anterior part of the distal clavicle to get a better cosmetic result. Post
      operatively the patient had an excellent range of motion without any further
      symptoms after six weeks and one year. Venous congestion was not more
      observable.In most of the cases dislocations of both ends of the clavicle are
      treated conservatively. We recommend an operative treatment especially in young
      and active patients to avoid re-dislocation and to archive better cosmetic
      results.

PMID- 22367520
TI  - [Risk of injury to children's fingers in power-operated motor vehicle windows].
AB  - BACKGROUND: This study examines the dimensions of children's fingers and the risk
      of jam injuries in a 4-mm gap between glass and gasket of power-operated motor
      vehicle windows. MATERIAL AND METHODS: The diameter of the proximal, middle, and
      distal phalanx and of the proximal and distal interphalangeal joint of each
      finger of the right hand of 160 children was measured in a cross-sectional
      investigation. Six different drawings in cross section of gaskets and glass
      window panes of current motor vehicle side door windows at a vertical gap of 4 mm
      were drawn in correct proportion. The larger actual width of the oblique gap
      between window glass and gasket was measured and related to the diameters of
      children's fingers. RESULTS: Almost all fingers and joints fit in the largest
      actual gap of 18 mm between glass and gasket of one seal design. CONCLUSION: The
      European guideline 74/60/EWG specifications currently pertaining to closing force
      restriction do not eliminate the risk of potentially serious injury to children's
      fingers in motor vehicle power windows.

PMID- 22367521
TI  - [Preventive bone mineral density measurement in postmenopausal women.
      Differentiation of treatment of recommendations Guidelines of the Umbrella
      Organization for Osteology ("Dachverband Osteologie")].
AB  - BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone
      densitometry (DXA) in postmenopausal women free of known skeletal disorders and
      without acute fracture. DVO guidelines were applied to define therapeutic
      indication. METHODS: The study included 94 women aged 59-81 years. Fracture or
      operation <=12 months, malignant tumor, ovariectomy, and drugs such as cortisone,
      strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were
      exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip
      was decisive. The indication for therapy was determined by evaluating age, BMD,
      and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal
      BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband
      Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy.
      Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated
      in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD
      with DXA provides a benefit for postmenopausal women. Combinatory assessment and
      consideration of other risk factors allows identification of women who might
      benefit from early treatment.

PMID- 22367522
TI  - [TEAM(r)-G (Trauma Evaluation and Management Germany). Serves as a basis for an
      interdisciplinary training in the emergency room].
AB  - BACKGROUND: The implementation of ATLS(r) in the daily routine of trauma
      management in the emergency department is a challenge. This goal cannot be
      reached by educating ATLS(r) to a few team members only. In order to enforce the
      implementation of ATLS(r) in a level I trauma centre, a generic in-house training
      was introduced in 2009 with inter-professional integration of all specialists of
      the trauma team. MATERIALS AND METHODS: The TEAM(r) course (trauma evaluation and
      management concept of the American College of Surgeons) was the theoretical basis
      of the training. This educational program was developed for medical students and
      multidisciplinary team members. Prior training, a questionnaire for self
      assessment was completed by n=84 team members to assess their knowledge about
      ATLS(r) principles. The hands-on training time was 90 min. N=10 members of the
      trauma team worked out three scenarios of multiple injured patients. These were
      provided as near-reality manikin simulations by a specialist trainer. After the
      training participants re-evaluated and analysed improvement by the training.
      Duration of trauma management and the number of missed injuries were analysed one
      year prior and one year after the training and served as a marker of the process
      and outcome quality of trauma care. RESULTS: Prior the training, 57% of trainees
      specified their knowledge related to the ATLS(r) can be improved. Their
      expectations were generally satisfied by the training. The mean time of trauma
      management in the ED could not be reduced one year after the training (36+/-16
      min) compared to one year prior the training (39+/-18 min), however, the
      detection of missed injuries (5.6% vs. 3.2%, p<0.05) was significantly diminished
      after the training. CONCLUSION: Apart form education of ATLS(r) providers the
      inauguration of an interdisciplinary and interprofessionel team training may
      enhance implementation of ATLS- algorithms into daily routine.

PMID- 22367524
TI  - Interview with Chi-Ming Che.

PMID- 22367523
TI  - [Handling modern imaging procedures in a high-tech operating room].
AB  - Operating rooms are the central unit in the hospital network in trauma centers.
      In this area, high costs but also high revenues are generated. Modern operating
      theater concepts as an integrated model have been offered by different companies
      since the early 2000s. Our hypothesis is that integrative concepts for operating
      rooms, in addition to improved operating room ergonomics, have the potential for
      measurable time and cost savings. In our clinic, an integrated operating room
      concept (I-Suite, Stryker, Duisburg) was implemented after analysis of the
      problems. In addition to the ceiling-mounted arrangement, the system includes an
      endoscopy unit, a navigation system, and a voice control system. In the first 6
      months (9/2005 to 2/2006), 112 procedures were performed in the integrated
      operating room: 34 total knee arthroplasties, 12 endoscopic spine surgeries, and
      66 inpatient arthroscopic procedures (28 shoulder and 38 knee reconstructions).
      The analysis showed a daily saving of 22-45 min, corresponding to 15-30% of the
      daily changeover times, calculated to account for potential savings in the
      internal cost allocation of 225-450 EUR. A commercial operating room concept was
      evaluated in a pilot phase in terms of hard data, including time and cost
      factors. Besides the described effects further savings might be achieved through
      the effective use of voice control and the benefit of the sterile handle on the
      navigation camera, since waiting times for an additional nurse are minimized. The
      time of the procedure of intraoperative imaging is also reduced due to the
      ceiling-mounted concept, as the C-arm can be moved freely in the operating
      theater without hindering cables. By these measures and ensuing improved
      efficiency, the initial high costs for the implementation of the system may be
      cushioned over time.

PMID- 22367525
TI  - For an Ethnomethodology of healthcare ethics.
AB  - This paper considers the utility of Ethnomethodology (EM) for the study of
      healthcare ethics as part of the empirical turn in Bioethics. I give a brief
      introduction to EM through its respecification of sociology, the specific view on
      the social world this generates and EM's posture of 'indifference'. I then take a
      number of EM concepts and articulate each in the context of an EM study of
      healthcare ethics in professional practice. Having given an overview of the
      relationship and perspective EM might bring to the professional practice of
      healthcare ethics I consider whether and how such an approach could be deployed.
      Whilst an ethnographic study might be problematic I suggest a number of
      alternative methods through which such EM research could be accomplished. I
      conclude with the suggestion that, as a particular approach to sociological
      research, EM offers good deal of potential for the empirical study of healthcare
      ethics in practice which could result in an improved reflexive understanding of
      professional ethical practices in bioethics. 

PMID- 22367526
TI  - Empirical fallacies in the debate on substituted judgment.
AB  - According to the Substituted Judgment Standard a surrogate decision maker ought
      to make the decision that the incompetent patient would have made, had he or she
      been competent. This standard has received a fair amount of criticism, but the
      objections raised are often wide of the mark. In this article we discuss three
      objections based on empirical research, and explain why these do not give us
      reason to abandon the Substituted Judgment Standard. 

PMID- 22367527
TI  - Spatial distribution and viability of nitrifying, denitrifying and ANAMMOX
      bacteria in biofilms of sponge media retrieved from a full-scale biological
      nutrient removal plant.
AB  - The spatial distribution and activities of nitrifying and denitrifying bacteria
      in sponge media were investigated using diverse tools, because understanding of
      in situ microbial condition of sponge phase is critical for the successful design
      and operation of sponge media process. The bacterial consortia within the media
      was composed of diverse groups including a 14.5% Nitrosomonas spp.-like ammonia
      oxidizing bacteria (AOB), 12.5% Nitrobacter spp.-like nitrite oxidizing bacteria
      (NOB), 2.0% anaerobic ammonium-oxidizing (ANAMMOX) bacteria and 71.0% other
      bacteria. The biofilm appeared to be most dense in the relatively outer region of
      the media and gradually decreased with depth, but bacterial viabilities showed
      space-independent feature. The fluorescent in situ hybridization results revealed
      that AOB and NOB co-existed in similar quantities on the side fragments of the
      media, which was reasonably supported by the microelectrode measurements showing
      the concomitant oxidation of NH(4) (+) and production of NO(3) (-) in this zone.
      However, a significantly higher fraction of AOB was observed in the center than
      side fragment. As with the overall biofilm density profile, the denitrifying
      bacteria were also more abundant on the side than in the center fragments.
      ANAMMOX bacteria detected throughout the entire depth offer another advantage for
      the removal of nitrogen by simultaneously converting NH(4) (+) and NO(2) (-) to
      nitrogen gas.

PMID- 22367528
TI  - Production of xylanase and beta-xylosidase from autohydrolysis liquor of corncob
      using two fungal strains.
AB  - Agroindustrial residues are materials often rich in cellulose and hemicellulose.
      The use of these substrates for the microbial production of enzymes of industrial
      interest is mainly due to their high availability associated with their low cost.
      In this work, corncob (CCs) particles decomposed to soluble compounds (liquor)
      were incorporated in the microbial growth medium through autohydrolysis, as a
      strategy to increase and undervalue xylanase and beta-xylosidase production by
      Aspergillus terricola and Aspergillus ochraceus. The CCs autohydrolysis liquor
      produced at 200  degrees C for 5, 15, 30 or 50 min was used as the sole carbon
      source or associated with untreated CC. The best condition for enzyme synthesis
      was observed with CCs submitted to 30 min of autohydrolysis. The enzymatic
      production with untreated CCs plus CC liquor was higher than with birchwood xylan
      for both microorganisms. A. terricola produced 750 total U of xylanase (144 h
      cultivation) and 30 total U of beta-xylosidase (96-168 h) with 0.75% untreated
      CCs and 6% CCs liquor, against 650 total U of xylanase and 2 total U of beta
      xylosidase in xylan; A. ochraceus produced 605 total U of xylanase and 56 total U
      of beta-xylosidase (168 h cultivation) with 1% untreated CCs and 10% CCs liquor
      against 400 total U of xylanase and 38 total U of beta-xylosidase in xylan. These
      results indicate that the treatment of agroindustrial wastes through
      autohydrolysis can be a viable strategy in the production of high levels of
      xylanolytic enzymes.

PMID- 22367529
TI  - Chitin and L(+)-lactic acid production from crab (Callinectes bellicosus) wastes
      by fermentation of Lactobacillus sp. B2 using sugar cane molasses as carbon
      source.
AB  - Crab wastes are employed for simultaneous production of chitin and L(+)-lactic
      acid by submerged fermentation of Lactobacillus sp. B2 using sugar cane molasses
      as carbon source. Response surface methodology was applied to design the culture
      media considering demineralization. Fermentations in stirred tank reactor (2L)
      using selected conditions produced 88% demineralization and 56% deproteinization
      with 34% yield of chitin and 19.5 gL(-1) of lactic acid (77% yield). The chitin
      purified from fermentation displayed 95% degree of acetylation and 0.81 and 1 +/-
      0.125% of residual ash and protein contents, respectively.

PMID- 22367530
TI  - Effects of carbon sources and feeding strategies on heparosan production by
      Escherichia coli K5.
AB  - This work aimed to develop an optimal carbon source feeding strategy to achieve
      maximal production of heparosan as a precursor of bioengineered heparin by
      Escherichia coli K5. Glycerol gave higher heparosan titer and productivity
      compared to glucose. The maximum heparosan production (187 mg/L) and heparosan
      productivity (5.19 mg/L/h) in glycerol-defined medium were 26.4% higher than the
      heparosan production (148 mg/L) and heparosan productivity (4.11 mg/L/h) in
      glucose-defined medium. DO-stat feeding approach as compared to pH-stat feeding,
      exponential feeding, exponential combined with pH-stat feeding, and constant rate
      feeding gave the highest heparosan titer at 8.63 g/L, which was nine times that
      of batch culture. The obtained optimal glycerol feeding strategy may be useful
      for the scaling-up of microbial heparosan production.

PMID- 22367531
TI  - Shoulder load during synchronous handcycling and handrim wheelchair propulsion in
      persons with paraplegia.
AB  - OBJECTIVE: To compare the shoulder load during handcycling and wheelchair
      propulsion under similar conditions of external power in persons with spinal cord
      injury. DESIGN: Cross-sectional. SUBJECTS: Eight men with spinal cord injury.
      METHODS: Kinetics and kinematics were measured during handbike and wheelchair
      propulsion at 25, 35, 45 and 55 W on a treadmill. Shoulder load (glenohumeral
      contact forces, relative muscle forces) was calculated with the Delft Shoulder
      and Elbow Model. RESULTS: At all power output levels, glenohumeral contact forces
      were significantly lower during handcycling compared with wheelchair propulsion
      (p < 0.001). At 55 W, the mean glenohumeral contact force was 345 N for hand
      cycling, whereas it was 585 N for wheelchair propulsion. Also, relative muscle
      forces were lower during handcycling. The largest differences between handbike
      and wheelchair propulsion were found in the supraspinatus (4.5% vs. 20.7%),
      infraspinatus (3.7% vs. 16.5%) and biceps (5.0% vs. 17.7%). CONCLUSION: Due to
      continuous force application in hand-cycling, shoulder load was lower compared
      with wheelchair propulsion. Furthermore, muscles that are prone to overuse
      injuries were less stressed during handcycling. Therefore, handcycling may be a
      good alternative for outdoor mobility and may help prevent overuse injuries of
      the shoulder complex.

PMID- 22367532
TI  - Vitamin D deficiency in burn patients.
AB  - Vitamin D deficiency has been reported in pediatric burn patients; however, no
      formal studies have been conducted in adult burn populations. The available
      literature on vitamin D status in burn patients has been reviewed. A literature
      search was conducted using MedlineTM, the Cochrane central register of controlled
      trials, and EMBASE to identify any trials of vitamin D deficiency in burn
      patients. Six published studies regarding vitamin D status in burn patients were
      found; however, five of these were in pediatric populations and several did not
      assess vitamin D levels as a major endpoint. Vitamin D deficiency has been
      demonstrated to result in itching, muscle weakness, and neuropathy, all of which
      are common postburn sequelae. The major source of vitamin D is synthesis in the
      skin with a small amount being absorbed through dietary intake. Population groups
      are at higher risk of vitamin D deficiency if they have inadequate exposure to UV
      light or reduced biosynthetic capability due to skin damage. Burn patients fall
      into both risk groups and also suffer common complaints that overlap with those
      reported by patients with vitamin D deficiency. Further research in adult burn
      patients is needed to determine the prevalence of deficiency in this population
      and whether vitamin D deficiency might influence postburn injury symptoms
      reported by patients.

PMID- 22367533
TI  - Long-term impact of sublethal atrazine perturbs the redox homeostasis in pea
      (Pisum sativum L.) plants.
AB  - Atrazine frequently contaminates soil, groundwater, rivers, and ponds. It is well
      know that acute doses (1-5 mM) of atrazine induce massive generation of singlet
      oxygen by blocking photosystem II. The sublethal concentrations of this
      herbicide, similar to those found in the environment, also reduce growth and
      disrupt photosynthesis in a long-term aspect, but exact mechanisms remain much
      uncertain. In this study the effects of environmentally relevant atrazine levels,
      ranging from 0.1 to 10 MUM, on pea plants were characterized for up to 20 days.
      The plants exposed to continuous influence of atrazine exhibited perturbed redox
      homeostasis with increases of the lipid peroxides, the total and oxidized
      glutathione pools and elevated guaiacol peroxidase and glutathione-S-transferase
      activities. In contrast, the long-term atrazine impact did not affect superoxide
      dismutase activity whereas the catalase was inhibited. The perturbations of the
      redox status and the recruitment of the antioxidant machinery imply that the
      sublethal atrazine concentrations alter the poise between production and
      scavenging of reactive oxygen species. Taken together these results show that the
      long-term impact of sublethal atrazine has hallmarks of oxidative stress most
      probably triggered by generation of singlet oxygen.

PMID- 22367534
TI  - Oligomerization of the reversibly glycosylated polypeptide: its role during rice
      plant development and in the regulation of self-glycosylation.
AB  - A multigenic family of self-glycosylating proteins named reversibly glycosylated
      polypeptides, designated as RGPs, have been usually associated with carbohydrate
      metabolism, although they are an enigma both at the functional, as well as at the
      structural level. In this work, we used biochemical approaches to demonstrate
      that complex formation is linked to rice plant development, in which class 1
      Oryza sativa RGP (OsRGP) would be involved in an early stage of growing plants,
      while class 2 OsRGP would be associated with a late stage linked to an active
      polysaccharide synthesis that occurs during the elongation of plant. Here, a
      further investigation of the complex formation of the Solanum tuberosum RGP
      (StRGP) was performed. Results showed that disulfide bonds are at least partially
      responsible for maintaining the oligomeric protein structure, so that the
      nonreduced StRGP protein showed an apparent higher molecular weight and a lower
      radioglycosylation of the monomer with respect to its reduced form. Hydrophobic
      cluster analysis and secondary structure prediction revealed that class 2 RGPs no
      longer maintained the Rossman fold described for class 1 RGP. A 3D structure of
      the StRGP protein resolved by homology modeling supports the possibility of
      intercatenary disulfide bridges formed by exposed cysteines residues C79, C303
      and C251 and they are most probably involved in complex formation occurring into
      the cell cytoplasm.

PMID- 22367535
TI  - Feasibility of mFOLFOX6 as the adjuvant treatment after curative resection of
      metastases from colorectal cancer in Japanese patients.
AB  - BACKGROUND: An oxaliplatin-based regimen as the adjuvant treatment for stage III
      colon cancer demonstrated a survival advantage over fluorouracil (FU) and
      leucovorin (LV) in the MOSAIC and NSABP C-07 trials. For adjuvant treatment after
      the resection of metastases from colorectal cancer), active chemotherapy regimens
      such as FOLFOX are recommended. However, the safety data of FOLFOX are
      insufficient for its use after metastasectomy of colorectal cancer in Japanese
      patients. The aim of this study was to evaluate the safety of mFOLFOX6 for
      adjuvant treatment after the resection of metastases from colorectal cancer.
      METHODS: Among 67 consecutive patients who received mFOLFOX6 as the adjuvant
      treatment after resection of metastases from colorectal cancer between September
      2002 and March 2009 in our institution, 51 patients who had not received
      preoperative chemotherapy were reviewed. The mFOLFOX6 treatment comprised
      oxaliplatin 85 mg/m(2) and l-leucovorin 200 mg/m(2) given intravenously over a 2
      h period on day 1, followed by a 5-FU bolus of 400 mg/m(2) and a 46-h infusion of
      5-FU 2400 mg/m(2), every 2 weeks for up to 12 cycles. RESULTS: National Cancer
      Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTC)
      grade 3-4 toxicities per patient were: peripheral neuropathy 8%, allergic
      reaction 4%, aspartate transaminase (AST) 4%, febrile neutropenia 4%, nausea 2%,
      anorexia 2%, fatigue 2%, alanine transaminase (ALT) 2%, bilirubin 2%, neutrophils
      49%, leukocytes 6%, and hemoglobin 2%; 71% of the patients completed the
      scheduled 12 cycles. CONCLUSION: Adjuvant therapy with mFOLFOX6 after resection
      of metastases from colorectal cancer is feasible for Japanese patients.

PMID- 22367536
TI  - Solid-state supramolecular assemblies consisting of planar charged species.
AB  - Pyrrole-based pi-conjugated anion-responsive molecules provided various planar
      anionic structures by complexation with halide anions, resulting in the formation
      of solid-state assemblies with planar counter cations and exhibiting various
      modes of charge-by-charge assembly depending on the substituents of the anion
      receptors.

PMID- 22367537
TI  - Sequencing of neuroblastoma identifies chromothripsis and defects in
      neuritogenesis genes.
AB  - Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system.
      The pathogenesis has for a long time been quite enigmatic, as only very few gene
      defects were identified in this often lethal tumour. Frequently detected gene
      alterations are limited to MYCN amplification (20%) and ALK activations (7%).
      Here we present a whole-genome sequence analysis of 87 neuroblastoma of all
      stages. Few recurrent amino-acid-changing mutations were found. In contrast,
      analysis of structural defects identified a local shredding of chromosomes, known
      as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are
      associated with a poor outcome. Structural alterations recurrently affected ODZ3,
      PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In
      addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were
      mutated, further implicating defects in neuritogenesis in neuroblastoma. Most
      tumours with defects in these genes were aggressive high-stage neuroblastomas,
      but did not carry MYCN amplifications. The genomic landscape of neuroblastoma
      therefore reveals two novel molecular defects, chromothripsis and neuritogenesis
      gene alterations, which frequently occur in high-risk tumours.

PMID- 22367538
TI  - Ageing: Sorting out the sirtuins.

PMID- 22367539
TI  - The mechanism of OTUB1-mediated inhibition of ubiquitination.
AB  - Histones are ubiquitinated in response to DNA double-strand breaks (DSB),
      promoting recruitment of repair proteins to chromatin. UBC13 (also known as
      UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A
      (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at
      DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub
      synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme,
      OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds
      preferentially to the UBC13~Ub thiolester. Residues amino-terminal to the OTU
      domain, which had been implicated in ubiquitin binding, are required for binding
      to UBC13~Ub and inhibition of K63Ub synthesis. Here we describe structural and
      biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We
      unexpectedly find that OTUB1 binding to UBC13~Ub is allosterically regulated by
      free ubiquitin, which binds to a second site in OTUB1 and increases its affinity
      for UBC13~Ub, while at the same time disrupting interactions with UEV1A in a
      manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13
      complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13~Ub
      conjugate show that binding of free ubiquitin to OTUB1 triggers conformational
      changes in the OTU domain and formation of a ubiquitin-binding helix in the N
      terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13~Ub to
      OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has
      been shown to be important for ubiquitin transfer. The N-terminal helix of OTUB1
      is positioned to interfere with UEV1A binding to UBC13, as well as with attack on
      the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis.
      OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a
      further component of inhibition. The general features of the inhibition mechanism
      explain how OTUB1 inhibits other E2 enzymes in a non-catalytic manner.

PMID- 22367540
TI  - A universal model for mobility and migration patterns.
AB  - Introduced in its contemporary form in 1946 (ref. 1), but with roots that go back
      to the eighteenth century, the gravity law is the prevailing framework with which
      to predict population movement, cargo shipping volume and inter-city phone calls,
      as well as bilateral trade flows between nations. Despite its widespread use, it
      relies on adjustable parameters that vary from region to region and suffers from
      known analytic inconsistencies. Here we introduce a stochastic process capturing
      local mobility decisions that helps us analytically derive commuting and mobility
      fluxes that require as input only information on the population distribution. The
      resulting radiation model predicts mobility patterns in good agreement with
      mobility and transport patterns observed in a wide range of phenomena, from long
      term migration patterns to communication volume between different regions. Given
      its parameter-free nature, the model can be applied in areas where we lack
      previous mobility measurements, significantly improving the predictive accuracy
      of most of the phenomena affected by mobility and transport processes.

PMID- 22367541
TI  - The translational landscape of mTOR signalling steers cancer initiation and
      metastasis.
AB  - The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein
      synthesis that couples nutrient sensing to cell growth and cancer. However, the
      downstream translationally regulated nodes of gene expression that may direct
      cancer development are poorly characterized. Using ribosome profiling, we uncover
      specialized translation of the prostate cancer genome by oncogenic mTOR
      signalling, revealing a remarkably specific repertoire of genes involved in cell
      proliferation, metabolism and invasion. We extend these findings by functionally
      characterizing a class of translationally controlled pro-invasion messenger RNAs
      that we show direct prostate cancer invasion and metastasis downstream of
      oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site
      inhibitor of mTOR, INK128, which reprograms this gene expression signature with
      therapeutic benefit for prostate cancer metastasis, for which there is presently
      no cure. Together, these findings extend our understanding of how the 'cancerous'
      translation machinery steers specific cancer cell behaviours, including
      metastasis, and may be therapeutically targeted.

PMID- 22367542
TI  - Strict evolutionary conservation followed rapid gene loss on human and rhesus Y
      chromosomes.
AB  - The human X and Y chromosomes evolved from an ordinary pair of autosomes during
      the past 200-300 million years. The human MSY (male-specific region of Y
      chromosome) retains only three percent of the ancestral autosomes' genes owing to
      genetic decay. This evolutionary decay was driven by a series of five
      'stratification' events. Each event suppressed X-Y crossing over within a
      chromosome segment or 'stratum', incorporated that segment into the MSY and
      subjected its genes to the erosive forces that attend the absence of crossing
      over. The last of these events occurred 30 million years ago, 5 million years
      before the human and Old World monkey lineages diverged. Although speculation
      abounds regarding ongoing decay and looming extinction of the human Y chromosome,
      remarkably little is known about how many MSY genes were lost in the human
      lineage in the 25 million years that have followed its separation from the Old
      World monkey lineage. To investigate this question, we sequenced the MSY of the
      rhesus macaque, an Old World monkey, and compared it to the human MSY. We
      discovered that during the last 25 million years MSY gene loss in the human
      lineage was limited to the youngest stratum (stratum 5), which comprises three
      percent of the human MSY. In the older strata, which collectively comprise the
      bulk of the human MSY, gene loss evidently ceased more than 25 million years ago.
      Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during
      the past 25 million years, despite its major structural differences to the human
      MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes
      that might enable intrachromosomal recombination and repair. We present an
      empirical reconstruction of human MSY evolution in which each stratum
      transitioned from rapid, exponential loss of ancestral genes to strict
      conservation through purifying selection.

PMID- 22367543
TI  - Re-emerging superconductivity at 48 kelvin in iron chalcogenides.
AB  - Pressure has an essential role in the production and control of superconductivity
      in iron-based superconductors. Substitution of a large cation by a smaller rare
      earth ion to simulate the pressure effect has raised the superconducting
      transition temperature T(c) to a record high of 55 K in these materials. In the
      same way as T(c) exhibits a bell-shaped curve of dependence on chemical doping,
      pressure-tuned T(c) typically drops monotonically after passing the optimal
      pressure. Here we report that in the superconducting iron chalcogenides, a second
      superconducting phase suddenly re-emerges above 11.5 GPa, after the T(c) drops
      from the first maximum of 32 K at 1 GPa. The T(c) of the re-emerging
      superconducting phase is considerably higher than the first maximum, reaching
      48.0-48.7 K for Tl(0.6)Rb(0.4)Fe(1.67)Se(2), K(0.8)Fe(1.7)Se(2) and
      K(0.8)Fe(1.78)Se(2).

PMID- 22367544
TI  - Circadian rhythms govern cardiac repolarization and arrhythmogenesis.
AB  - Sudden cardiac death exhibits diurnal variation in both acquired and hereditary
      forms of heart disease, but the molecular basis of this variation is unknown. A
      common mechanism that underlies susceptibility to ventricular arrhythmias is
      abnormalities in the duration (for example, short or long QT syndromes and heart
      failure) or pattern (for example, Brugada's syndrome) of myocardial
      repolarization. Here we provide molecular evidence that links circadian rhythms
      to vulnerability in ventricular arrhythmias in mice. Specifically, we show that
      cardiac ion-channel expression and QT-interval duration (an index of myocardial
      repolarization) exhibit endogenous circadian rhythmicity under the control of a
      clock-dependent oscillator, kruppel-like factor 15 (Klf15). Klf15
      transcriptionally controls rhythmic expression of Kv channel-interacting protein
      2 (KChIP2), a critical subunit required for generating the transient outward
      potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT
      variation, abnormal repolarization and enhanced susceptibility to ventricular
      arrhythmias. These findings identify circadian transcription of ion channels as a
      mechanism for cardiac arrhythmogenesis.

PMID- 22367545
TI  - Type VI secretion requires a dynamic contractile phage tail-like structure.
AB  - Type VI secretion systems are bacterial virulence-associated nanomachines
      composed of proteins that are evolutionarily related to components of
      bacteriophage tails. Here we show that protein secretion by the type VI secretion
      system of Vibrio cholerae requires the action of a dynamic intracellular tubular
      structure that is structurally and functionally homologous to contractile phage
      tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the
      type VI secretion system cycle between assembly, quick contraction, disassembly
      and re-assembly. Whole-cell electron cryotomography further shows that the
      sheaths appear as long tubular structures in either extended or contracted
      conformations that are connected to the inner membrane by a distinct basal
      structure. These data support a model in which the contraction of the type VI
      secretion system sheath provides the energy needed to translocate proteins out of
      effector cells and into adjacent target cells.

PMID- 22367546
TI  - The sirtuin SIRT6 regulates lifespan in male mice.
AB  - The significant increase in human lifespan during the past century confronts us
      with great medical challenges. To meet these challenges, the mechanisms that
      determine healthy ageing must be understood and controlled. Sirtuins are highly
      conserved deacetylases that have been shown to regulate lifespan in yeast,
      nematodes and fruitflies. However, the role of sirtuins in regulating worm and
      fly lifespan has recently become controversial. Moreover, the role of the seven
      mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in
      regulating lifespan is unclear. Here we show that male, but not female,
      transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer
      lifespan than wild-type mice. Gene expression analysis revealed significant
      differences between male Sirt6-transgenic mice and male wild-type mice:
      transgenic males displayed lower serum levels of insulin-like growth factor 1
      (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels
      of major components of IGF1 signalling, a key pathway in the regulation of
      lifespan. This study shows the regulation of mammalian lifespan by a sirtuin
      family member and has important therapeutic implications for age-related
      diseases.

PMID- 22367547
TI  - Gain control by layer six in cortical circuits of vision.
AB  - After entering the cerebral cortex, sensory information spreads through six
      different horizontal neuronal layers that are interconnected by vertical axonal
      projections. It is believed that through these projections layers can influence
      each other's response to sensory stimuli, but the specific role that each layer
      has in cortical processing is still poorly understood. Here we show that layer
      six in the primary visual cortex of the mouse has a crucial role in controlling
      the gain of visually evoked activity in neurons of the upper layers without
      changing their tuning to orientation. This gain modulation results from the
      coordinated action of layer six intracortical projections to superficial layers
      and deep projections to the thalamus, with a substantial role of the
      intracortical circuit. This study establishes layer six as a major mediator of
      cortical gain modulation and suggests that it could be a node through which
      convergent inputs from several brain areas can regulate the earliest steps of
      cortical visual processing.

PMID- 22367548
TI  - Exceptionally old mice are highly resistant to lipoxidation-derived molecular
      damage.
AB  - Membrane unsaturation plays an important role in the aging process and the
      determination of inter-species animal longevity. Furthermore, the accumulation of
      oxidation-derived molecular damage to cellular components particularly in the
      nervous and immune systems over time leads to homeostasis loss, which highly
      influences age-related morbidity and mortality. In this context, it is of great
      interest to know and discern the degree of membrane unsaturation and the steady
      state levels of oxidative damage in both physiological systems from long-lived
      subjects. In the present work, adult (28 +/- 4 weeks), old (76 +/- 4 weeks) and
      exceptionally old (128 +/- 4 weeks) BALB/c female mice were used. Brain and
      spleen were analysed for membrane fatty acid composition and specific markers of
      protein oxidation, glycoxidation and lipoxidation damage, i.e. glutamic
      semialdehyde, aminoadipic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine
      and malondialdehyde-lysine, by gas chromatography-mass spectrometry. The results
      showed significantly lower peroxidizability index in brain and spleen from
      exceptionally old animals when compared to old specimens. The higher membrane
      resistance to lipid peroxidation and lower lipoxidation-derived molecular damage
      found in exceptionally old animals was associated with a significantly lower
      desaturase activity and peroxisomal beta-oxidation. Protein oxidation markers in
      brain and spleen from adult and exceptionally old animals showed similar levels,
      which were higher in old mice. In addition, the higher levels of the
      glycoxidation-derived marker observed in exceptionally old animals, as well as in
      adult mice, could be considered as a good indicator of a better bioenergetic
      state of these animals when compared to the old group. In conclusion, low lipid
      oxidation susceptibility and maintenance of adult-like protein lipoxidative
      damage could be key mechanisms for longevity achievement.

PMID- 22367550
TI  - Longitudinal myocardial deformation is selectively decreased after pediatric
      cardiac transplantation: a comparison of children 1 year after transplantation
      with normal subjects using velocity vector imaging.
AB  - The transplanted heart experiences numerous hemodynamic changes during and after
      cardiac transplantation. This study sought to evaluate the left ventricular
      myocardial mechanics in the pediatric heart transplant population using Velocity
      Vector Imaging (VVI). This study retrospectively evaluated 28 heart transplant
      recipients by echocardiography 12 months after transplantation. Echocardiograms
      from 28 age- and gender-matched subjects were used as a control group. Peak
      global longitudinal and circumferential left ventricular strain, systolic strain
      rate, and diastolic strain rate were obtained. Student's t tests were used to
      assess differences between the two groups (defined as p <= 0.05). The peak global
      left ventricular longitudinal strain was lower in the transplant group (17.21%)
      than in the control group (22.14%). The transplant and control groups did not
      differ significantly in terms of their peak global circumferential strain (20.28%
      vs. 20.79%, respectively). Similar results were observed for longitudinal and
      circumferential systolic and diastolic strain rates. The transplant patients
      showed statistically significant reductions in all peak global longitudinal
      measures compared with those of the control subjects. Circumferential myocardial
      deformation appears to be preserved in transplant recipients. This could suggest
      evidence of ischemia given the known myocardial fiber arrangement of longitudinal
      fibers toward the endocardial surface, which is also more distal in the coronary
      arterioles.

PMID- 22367549
TI  - A molecular and proteomic investigation of proteins rapidly released from
      triticale pollen upon hydration.
AB  - Analysis of Triticale (*Triticosecale Wittmack cv. AC Alta) mature pollen
      proteins quickly released upon hydration was performed using two-dimensional gel
      electrophoresis followed by mass spectrometry. A total of 17 distinct protein
      families were identified and these included expansins, profilins, and various
      enzymes, many of which are pollen allergens. The corresponding genes were
      obtained and expression studies revealed that the majority of these genes were
      only expressed in developing anthers and pollen. Some genes including glucanase,
      glutathione peroxidase, glutaredoxin, and a profilin were found to be widely
      expressed in different reproductive and vegetative tissues. Group 11 pollen
      allergens, polygalacturonase, and actin depolymerizing factor were characterized
      for the first time in the Triticeae. This study represents a distinctive
      combination of proteomic and molecular analyses of the major cereal pollen
      proteins released upon hydration and therefore at the forefront of pollen-stigma
      interactions.

PMID- 22367551
TI  - A novel technique for zero-fluoroscopy catheter ablation used to manage Wolff
      Parkinson-White syndrome with a left-sided accessory pathway.
AB  - Conventional catheter ablation of cardiac arrhythmias is associated with the
      potential adverse effects of low-dose ionizing radiation on both patients and
      laboratory personnel. Due to the greater radiation sensitivity and the longer
      life expectancy of children, reduction of radiation exposure for them is of
      particular importance. A novel technique for zero-fluoroscopy catheter ablation
      is described using real-time tissue-tip contact force measurements for a 10-year
      old boy who had Wolff-Parkinson-White syndrome with a left-sided accessory
      pathway.

PMID- 22367552
TI  - Ketogenic diet: rapid onset of selenium deficiency-induced cardiac
      decompensation.
AB  - Selenium-deficiency cardiomyopathy is a known secondary complication from long
      term treatment with a ketogenic diet for medical refractory epilepsy. Our
      patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a
      normal selenium level before starting the diet, but he shortly thereafter
      developed acute reversible cardiomyopathy and ventricular tachycardia, which was
      unmasked during a hospitalization for an elective operative procedure. His
      cardiomyopathy was suspected to be secondary to a selenium-deficient state and
      was confirmed by way of a markedly low serum selenium level and supported by
      rapid improvement with the initiation of selenium supplementation and cessation
      of the ketogenic diet. For patients being initiated on a ketogenic diet, current
      screening guidelines call for baseline and follow-up selenium levels every 3
      months during the first year along with RDA selenium supplementation, which is 30
      mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our
      patient underwent elective surgery before his planned 3-month selenium level
      check and had potentially preventable complications. Secondary to this
      experience, we suggest that all patients initiated on a ketogenic diet should
      have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium
      level determined before any elective surgery. These steps would prevent
      unnecessary perioperative morbidity and mortality.

PMID- 22367553
TI  - Electrophysiological patterning of the heart.
AB  - In the adult heart, electrophysiological heterogeneity is present to guide
      activation and contraction. A change in electrophysiological heterogeneity, for
      example, during disease, can contribute to arrhythmogenesis. During development,
      spatial and temporal patterns of transcriptional activity regulate the localized
      expression of ion channels that cause electrophysiological heterogeneity
      throughout the heart. If we gain insight into the regulating processes that
      generate the electrophysiological characteristics and factors involved during
      development, we can use this knowledge in the search for new therapeutic targets.
      In this review, we discuss which factors guide the electrical patterning of
      atrioventricular conduction system and ventricles and how this patterning relates
      to arrhythmogenic disease in patients.

PMID- 22367555
TI  - Highly flexible capacitive strain gauge for continuous long-term blood pressure
      monitoring.
AB  - An innovative procedure for measuring blood pressure, with none of the
      disadvantages of current procedures, is proposed. A highly-flexible capacitive
      strain gauge has been designed to measure changes in the diameter of a blood
      vessel; such changes are indicative of blood pressure. The sensor is implanted
      and wrapped around an arterial blood vessel during the normal course of a
      surgical procedure. In vivo tests, demonstrating the feasibility of this concept,
      are reported, along with in vitro tests and notes on sensor design and
      fabrication. These continuous blood pressure monitoring sensors may be used for a
      continuous long-term monitoring of blood pressure and pulse. They may also be
      combined with a real-time nerve stimulation technique or a course of medication
      to create a closed-loop system for blood-pressure control.

PMID- 22367554
TI  - Atrial fibrillation in two adolescents.
AB  - Idiopathic atrial fibrillation (AF) in adolescents is extremely rare and has
      usually been associated with structural heart disease. We present two cases of
      symptomatic AF in adolescents without any identifiable etiology. No definitive
      guidelines are available for management of such patients.

PMID- 22367556
TI  - Improvement in cell capture throughput using parallel bioactivated microfluidic
      channels.
AB  - Optimization of targeted cell capture with microfluidic devices continues to be a
      challenge. On the one hand, microfluidics allow working with microliter volumes
      of liquids, whereas various applications in the real world require detection of
      target analyte in large volumes, such as capture of rare cell types in several ml
      of blood. This contrast of volumes (microliter vs. ml) has prevented the
      emergence of microfluidic cell capture sensors in the clinical setting. Here, we
      study the improvement in cell capture and throughput achieved using parallel
      bioactivated microfluidic channels. The device consists of channels in parallel
      with each other tied to a single channel. We discuss fabrication and testing of
      our devices, and show the ability for an improvement in throughput detection of
      target cells.

PMID- 22367558
TI  - Restaging transurethral resection of bladder tumor for high-risk stage Ta and T1
      bladder cancer.
AB  - Bladder cancer is the most common malignancy of the urinary tract. About 75%-85%
      of patients present with non-muscle-invasive bladder cancer (NMIBC). However,
      patients with pT1 tumors, as well as all those with high-grade disease, make up a
      subset with a high-risk of recurrence and disease progression. Although still
      regarded as the gold standard, clinical evidence from contemporary published
      series clearly demonstrates that transurethral resection of tumor (TUR) is a
      procedure far from optimal, highlighting its limitations and the need for further
      diagnostic accuracy. Routine use of a restaging TUR (re-TUR), supported by the
      American Urological Association and European Association of Urology guidelines,
      detects residual tumor in a significant number of cases after initial TUR. It
      provides a more accurate staging of the disease and, consequently, helps to guide
      its treatment. Recent years have seen rapid development of novel optical
      techniques aimed to optimize resection. Routine implementation of these novel
      techniques in the context of re-TUR is promising and may potentially result in
      more tumors being identified and completely resected, leading to significantly
      lower residual tumor rates than with the standard white-light TUR. This article
      will focus on re-TUR in the management of high-risk NMIBC, with an up-to-date
      review of the available literature and detailed analysis of the published series.

PMID- 22367559
TI  - Synthesis of tetrahydro-beta-carbolines via isomerization of N-allyltryptamines:
      a metal-catalyzed variation on the Pictet-Spengler theme.
AB  - An efficient and broadly applicable alternative to the classical Pictet-Spengler
      synthesis of tetrahydro-beta-carbolines is presented. The method relies on metal
      catalyzed isomerization of allylic amines to form reactive iminium intermediates
      which can be trapped by a tethered indole nucleophile.

PMID- 22367557
TI  - Roles of AMP-activated protein kinase in Alzheimer's disease.
AB  - AMP-activated protein kinase (AMPK), a master regulator of cellular energy
      homeostasis and a central player in glucose and lipid metabolism, is potentially
      implicated in the pathogenesis of Alzheimer's disease (AD). AMPK activity
      decreases in AD brain, indicating decreased mitochondrial biogenesis and
      function. Emerging evidence demonstrates that AMPK activation is a potential
      target for improving perturbed brain energy metabolism that is involved in the
      pathogenesis of AD. The roles of AMPK in the pathogenesis of AD include beta
      amyloid protein (Abeta) generation and tau phosphorylation. In particular, AMPK
      may regulate Abeta generation through modulating neuronal cholesterol and
      sphingomyelin levels and through regulating APP distribution in the lipid rafts.
      AMPK is activated by phosphorylation of Thr-172 by LKB1 complex in response to
      increase in the AMP/ATP ratio and by calmodulin-dependent protein kinase kinase
      beta in response to elevated Ca(2+) levels, which contributes to regulating Abeta
      generation. AMPK is a physiological tau kinase and can increase the
      phosphorylation of tau at Ser-262. AMPK can also directly phosphorylate tau at
      Thr-231 and Ser-396/404. Furthermore, AMPK activation decreases mTOR signaling
      activity to facilitate autophagy and promotes lysosomal degradation of Abeta.
      However, AMPK activation has non-neuroprotective property and may lead to
      detrimental outcomes, including Abeta generation and tau phosphorylation.
      Therefore, it is still unclear whether AMPK could serve a potential therapeutic
      target for AD, and hence, further studies will be needed to clarify the role of
      AMPK in AD.

PMID- 22367561
TI  - Alexithymia and gambling: a risk factor for all gamblers?
AB  - The purpose of this study was to investigate alexithymia (in relation with
      depression) in three groups of French gamblers (n = 186) recruited in their
      gambling location: at the racetracks (n = 80 males; mean age 28.1 years), in the
      slot machine rooms (n = 65; 29 males, 36 females; mean age 34.6 years), and in
      the traditional gaming rooms (n = 41 males; mean age 36 years). Gambling behavior
      was measured by the South Oaks Gambling Screen and DSM-IV criteria for
      pathological gambling, Alexithymia by the Toronto Alexithymia Scale (TAS-20) and
      depression with the Beck Depression Inventory (BDI-13). For racetracks and slot
      machine gambling, pathological gamblers differed from non-pathological gamblers,
      regarding their alexithymia scores. These results remained stable after
      controlling for depression scores among the racetracks gamblers only. The
      relationship between alexithymia and depression depends on the type of
      pathological gambler. These findings are consistent with the idea of identifying
      clinically distinct subgroups of gamblers.

PMID- 22367563
TI  - The good and the bad of poisonous plants: an introduction to the USDA-ARS
      Poisonous Plant Research Laboratory.
AB  - This article provides an overview of the Poisonous Plant Research Laboratory
      (PPRL), about the unique services and activities of the PPRL and the potential
      assistance that they can provide to plant poisoning incidences. The PPRL is a
      federal research laboratory. It is part of the Agricultural Research Service, the
      in-house research arm of the U.S. Department of Agriculture. The mission of the
      PPRL is to identify toxic plants and their toxic compounds, determine how the
      plants poison animals, and develop diagnostic and prognostic procedures for
      poisoned animals. Furthermore, the PPRL's mission is to identify the conditions
      under which poisoning occurs and develop management strategies and treatments to
      reduce losses. Information obtained through research efforts at the PPRL is
      mostly used by the livestock industry, natural resource managers, veterinarians,
      chemists, plant and animal scientists, extension personnel, and other state and
      federal agencies. PPRL currently has 9 scientists and 17 support staff,
      representing various disciplines consisting of toxicology, reproductive
      toxicology, veterinary medicine, chemistry, animal science, range science, and
      plant physiology. This team of scientists provides an interdisciplinary approach
      to applied and basic research to develop solutions to plant intoxications. While
      the mission of the PPRL primarily impacts the livestock industry, spinoff
      benefits such as development of animal models, isolation and characterization of
      novel compounds, elucidation of biological and molecular mechanisms of action,
      national and international collaborations, and outreach efforts are significant
      to biomedical researchers. The staff at the PPRL has extensive knowledge
      regarding a number of poisonous plants. Although the focus of their knowledge is
      on plants that affect livestock, oftentimes, these plants are also poisonous to
      humans, and thus, similar principles could apply for cases of human poisonings.
      Consequently, the information provided herein could be of benefit to healthcare
      providers for human cases as well.

PMID- 22367564
TI  - The puzzle of kidney dysfunction in heart failure: an introduction.
AB  - Heart failure and kidney disease often coexist, and each of the two conditions
      may lead to progression of the other. Kidney dysfunction is an independent
      prognostic factor in patients with either acute or chronic heart failure.
      Worsening renal function may be related with poorer outcomes as well. Multiple
      mechanisms are involved in the cardio-renal interaction, including hemodynamic
      abnormalities, neurohormonal and inflammatory activation, oxidative stress,
      anemia, and abnormalities in mineral and vitamin D metabolism. Serum creatinine
      has limitations for the assessment of kidney function in patients with heart
      failure as its short-term changes are dependent on hemodynamic changes and fluid
      status. New biomarkers of glomerular and tubular function might allow an earlier
      and more accurate detection of worsening renal function.

PMID- 22367565
TI  - Population pharmacokinetics of mizoribine in pediatric recipients of renal
      transplantation.
AB  - BACKGROUND: An immunosuppressive agent, mizoribine, is excreted predominantly in
      the urine. The aim of this study was to investigate the pharmacokinetic
      variability of mizoribine in pediatric recipients of renal transplantation.
      METHODS: Pharmacokinetic data for population analysis were collected from 51
      recipients (32 males and 19 females) treated with oral administration of
      mizoribine (0.83-5.56 mg/day/kg). The population pharmacokinetic parameters of
      mizoribine were estimated using a nonlinear mixed effects model program. RESULTS:
      The pharmacokinetics of mizoribine in pediatric recipients of renal
      transplantation was well described by a one-compartment model with first-order
      absorption. The mean value of the absorption lag time (ALAG) and absorption rate
      constant (K (A)) was estimated to be 0.363 h and 0.554 h(-1), respectively.
      Apparent volume of distribution (V/F) was modeled as a function of body weight
      (WT), and the mean value was estimated to be 1.03 . WT L. Oral clearance (CL/F)
      was modeled as a function of creatinine clearance (CL(cr)), and the mean value
      was estimated to be 2.81 . CL(cr) . 60/1000 L/h. In addition, there was a
      positive correlation between CL(cr)-corrected CL/F and WT-corrected V/F in the
      pediatric recipients, indicating large interindividual variability in the
      bioavailability (F) of mizoribine. CONCLUSION: The present findings indicated
      that the rate of renal excretion and also the extent of intestinal absorption of
      mizoribine are responsible for the large interindividual pharmacokinetic
      variability of the drug.

PMID- 22367566
TI  - Significance of rehabilitative management during the critical period for motor
      recovery in intracerebral hemorrhage: a case report.
AB  - OBJECTIVE: The majority of motor recovery following stroke is known to occur
      within 3-6 months after onset; this period is therefore regarded as critical for
      motor recovery in stroke patients. We report here a case of a patient with
      intracerebral haemorrhage who showed changes in the affected motor function and
      in the damaged corticospinal tract (CST) at the primary motor cortex (M1) during
      rehabilitative management. CASE DESCRIPTION: A 51-year-old woman underwent
      decompressive craniectomy and removal of haematoma due to a rupture of an
      arteriovenous malformation. Brain magnetic resonance imaging revealed a
      leukomalactic lesion at the fronto-parietal cortex centred on the precentral
      knob. Diffusion tensor imaging data were acquired 4 times (5, 8, 11 and 18 weeks
      after onset) and she started rehabilitation for right hemiplegia at 5 weeks after
      onset. RESULTS: We found close relationships between changes in the CST branch
      from M1 on diffusion tensor tractography, the state of motor weakness, and the
      rehabilitative management: the CST branch from M1 was observed concurrently with
      motor recovery and the process of rehabilitation. CONCLUSION: This case report
      indicates the importance of active and comprehensive rehabilitative management
      during the critical period for motor recovery in stroke patients.

PMID- 22367567
TI  - Appropriate therapies predict long-term mortality in primary and secondary
      prevention of sudden cardiac death.
AB  - BACKGROUND: Less than 50% of patients implanted with an implantable cardioverter
      defibrillator (ICD) receive device therapy during the follow-up. The aim of our
      study was to prospectively evaluate the predictive role of appropriate ICD
      therapy on long-term survival of patients implanted for primary or secondary
      sudden death prevention. METHODS: From 2002 to 2003, 139 consecutive patients
      [mean age 66+/-9 years, male 77%, ischemic heart disease 56%, New York Heart
      Association functional class >II (74%), primary prevention 74%, mean left
      ventricular ejection fraction 30+/-9%, cardiac resynchronization ICD 65%] were
      enrolled. We collected and evaluated device therapies for at least 18 months and
      recorded survival status for more than 5 years. RESULTS: Over a median follow-up
      of 18 months, 54 (39%) patients received at least one ICD intervention, with 28
      patients receiving only appropriate ICD therapies, 13 only inappropriate
      therapies and 13 receiving both therapies. At a mean follow-up of 63+/-12 months,
      30 deaths occurred in 130 patients (23%); for nine patients, we had no survival
      status information. Death was classified as cardiac in 22 (73%) patients, the
      most common cause was progressive heart failure. In a Cox proportional regression
      model, an appropriate ICD therapy was associated with a significant increase in
      the subsequent risk of death (hazard ratio 3.02, P=0.003). CONCLUSION: In
      patients implanted with ICD or cardiac resynchronization therapy with ICD
      devices, for primary or secondary sudden cardiac death prevention, appropriate
      ICD therapy predicts a three-fold greater risk of death.

PMID- 22367568
TI  - Endovascular treatment of descending thoracic aortic rupture:  mid- to long-term
      results in a single-centre registry.
AB  - AIMS: To update our experience with descending thoracic aortic rupture (DTAR)
      endovascular repair over a 6-year period. METHODS: This was a prospective, non
      randomized, single-centre study. We included all patients diagnosed with rupture
      of the thoracic aorta, who underwent endovascular grafting between January 2005
      and January 2011. Data were analysed using SPSS version 15.0. RESULTS: During the
      study interval 25 patients were diagnosed with DTAR. Sixteen patients with
      ruptured degenerative aneurysm (64%), four traumatic transection (16%), three
      acute complicated type B dissection (12%) and two acute complicated penetrating
      ulcer (8%). Nineteen patients (76%) were men, six women; the mean age was 62.96
      (+/-19.75) years. At admission, mean standard euroSCORE was 8.46 (+/-3.55), and
      mean APACHE II 14.96 (+/-8.53). Emergent endovascular stent grafting was
      successfully performed in all patients, no conversion to open repair was
      necessary. Mortality at Intensive Care Unit was 16% (four patients). Overall
      follow-up (mean 26.6 months, range 3-68) mortality in our series was 28%. Only
      one patient suffered a severe neurological complication (stroke). Late
      complications of endovascular procedure and need for reoperation appeared in one
      patient because of a secondary leak. CONCLUSIONS: Although this study is not a
      comparative analysis of DTAR, mortality and morbidity rates were lower than
      previously reported with emergent open surgical repair. One-year treatment
      results indicate a low incidence of graft-related complications. Endovascular
      treatment of the thoracic aortic rupture should be considered feasible and well
      tolerated in the short and medium term.

PMID- 22367569
TI  - Transcatheter vs. surgical aortic valve replacement:  a retrospective analysis
      assessing clinical effectiveness and safety.
AB  - OBJECTIVE: To compare, in terms of clinical effectiveness and safety, patients
      who underwent transcatheter aortic valve implantation (TAVI) with those who
      underwent surgical aortic valve replacement (S-AVR) for the treatment of severe
      aortic stenosis during the same period. METHODS: One hundred and eighty-seven
      consecutive patients were included: 81 with S-AVR and 106 with TAVI. Primary and
      secondary outcomes were reported in accordance with published reporting
      guidelines for valve surgery. A propensity matching model was computed in the
      attempt to reduce confounding effects of covariates. RESULTS: Thirty-day
      mortality and morbidity, as well as follow-up events, did not differ between the
      two therapeutic options, except for ICU stay, in favor of TAVI, and occurrence of
      pleural effusions, in favor of S-AVR. TAVI accomplished significant mean aortic
      gradient reduction (better than S-AVR in the immediate postoperative and at least
      comparable at follow-up) and improvement in valve area and functional class
      (always higher than S-AVR). Although for the first year, survival was at least
      comparable between TAVI and S-AVR (both whole and matched groups); at later
      times, TAVI all-cause and noncardiac mortality was higher in the whole sample, as
      expected from age and comorbidities of TAVI patients. At later follow-up, in the
      matched subsamples, 1-year mortality rates were replicated, with a significantly
      higher incidence of cardiac deaths in S-AVR patients. CONCLUSION: TAVI morbidity
      and mortality registered in this series are lower than those estimated for
      conventional surgery in high-risk patients and compare to those associated with S
      AVR in good surgical candidates.

PMID- 22367570
TI  - Congenital coronary anomalies in Takotsubo-like syndrome:  a rare association.

PMID- 22367571
TI  - The importance of exercise echocardiography for clinical decision making in
      primary mitral regurgitation.
AB  - Primary mitral regurgitation is generally an insidious disease with late onset of
      symptoms. Current European and American guidelines recommend surgery in severe
      primary mitral regurgitation when symptoms, overt left ventricular dysfunction,
      pulmonary hypertension or atrial fibrillation, occur. However, recent large
      studies reported an improved outcome in asymptomatic patients with severe mitral
      regurgitation referred for early mitral valve repair despite the risk of
      operative mortality or mitral valve replacement. Moreover, primary mitral
      regurgitation appears to have an important dynamic character in up to one-third
      of patients. This article provides an overview of the incremental evidence of the
      ability of exercise echocardiography to assess the functional repercussions of
      mitral regurgitation and the identification of high-risk patients who might
      benefit from early referral for surgery.

PMID- 22367572
TI  - Two is company, three is a crowd.
AB  - The use of pacemakers and central venous catheters (CVC) has become commonplace
      in the field of medicine. In the past, superior vena cava (SVC) syndrome was
      almost always associated with malignant occlusion of the SVC. However, with the
      increased use of pacemakers and implantable cardioverter-defibrillators (ICDs)
      almost 30% of all cases are related to the use of intravascular devices today. We
      present a case of SVC syndrome in a young patient with prior permanent pacemaker
      implantation who underwent CVC placement prior to surgery for hypertrophic
      cardiomyopathy.

PMID- 22367573
TI  - Isolated bicuspid pulmonary valve in adult diagnosed by three-dimensional
      transthoracic echocardiography.
AB  - Isolated bicuspid pulmonary valve is a rare arterial valve anomaly with very few
      reports in the literature, which regard overall cases of postmortem diagnosis.
      However, the true incidence of bicuspid pulmonary valve could be underestimated
      because of the difficulty in imaging pulmonary valve morphology with conventional
      two-dimensional transthoracic echocardiography (TTE). We report a case of
      isolated bicuspid pulmonary valve in an adult diagnosed by three-dimensional TTE.
      Off line multidimensional analysis of full-volume 3D allowed to obtain a short
      axis view of pulmonary valve showing a bicuspid valve characterized by an
      anterior and a posterior cups, normally thickened and with preserved systolic
      opening.

PMID- 22367574
TI  - Edema index established by a segmental multifrequency bioelectrical impedance
      analysis provides prognostic value in acute heart failure.
AB  - OBJECTIVES: A segmental multifrequency bioelectrical impedance analysis (SMBIA)
      is a noninvasive and reproducible modality for estimating the fluid state. The
      aim of this study was to test whether the SMBIA-derived edema index provides
      prognostic value in patients hospitalized due to acute heart failure (AHF).
      METHODS: To estimate the 6-month prognostic value of the predischarge edema index
      in patients hospitalized due to AHF, 112 patients were consecutively enrolled.
      Both predischarge edema index and B-type natriuretic peptide (BNP) were measured.
      Outcome follow-up focused on heart failure-related and all-cause re
      hospitalizations and all events. RESULTS: On the basis of a cutoff value of edema
      index of 0.390, patients were separated into two groups: edema index more than
      0.390 (n = 44) and edema index of 0.390 or less (n = 68). Compared with patients
      with edema index 0.390 or less, those with edema index of more than 0.390 were
      older, had lower blood albumin and hemoglobin levels, and had higher predischarge
      BNP levels, functional class, incidence of diabetes mellitus, valvular cause, and
      diuretic use. Although edema indexes were correlated with BNP levels (r = 0.47, P
      < 0.0001), a mismatch was noted in 33 (29%) patients. Univariate and multivariate
      analysis showed that an edema index of more than 0.390 predicted a higher
      incidence of heart failure-related re-hospitalization [odds ratio (OR) = 4.14,
      confidence interval (CI) = 1.05-15.28, P = 0.04] and all events (OR = 3.97, CI =
      1.4-11.25, P = 0.01). The edema index provided a prognostic value superior to
      that of BNP. Reducing the edema index in high-risk patients resulted in fewer
      heart failure-related re-hospitalizations (OR = 0.81, CI = 0.77-0.84, P < 0.001)
      and all events (OR = 0.8, CI = 0.76-0.85, P < 0.001). CONCLUSION: Edema index
      provides 6-month prognostic values in patients hospitalized due to AHF. Reducing
      the edema index in high-risk patients results in better outcomes.

PMID- 22367575
TI  - Long-term follow-up of DDDR closed-loop cardiac pacing for the prevention of
      recurrent vasovagal syncope.
AB  - AIMS: Vasovagal syncope (VVS) is a common disorder characterized by a drop in
      blood pressure accompanied with bradycardia; although it is generally considered
      a benign condition, some patients may be highly symptomatic despite general
      counselling and/or pharmacological therapy. Closed-loop stimulation (CLS),
      responding to myocardial contraction dynamics, demonstrated effectiveness in
      short-term prevention of recurrent VVS. The aim of this study was to evaluate CLS
      pacing in a long-term follow-up. METHODS: The study involved 35 patients (mean
      age 59 +/- 15 years) with 3 years' follow-up (mean 61 +/- 35 months). We compared
      syncopal events and presyncopes before and after CLS implantation. Mean number of
      syncopes for patients was six (range 1-24; 212 syncopal spells registered) before
      pacemaker implantation. RESULTS: At follow-up, 29 of 35 patients (83%) were
      asymptomatic; one patient experienced recurrent loss of consciousness but
      reported an improvement in the quality of life (one syncope or presyncope per
      month after CLS, vs. one syncope per week and daily presyncopes before CLS). Five
      patients experienced syncopal recurrences after CLS (range: 1-7, with a total of
      15 episodes); in all the cases, the number of post-CLS syncopes was significantly
      lower. CONCLUSION: Our study seems to confirm previous results of short-term
      trials: DDDR-CLS pacing is an extremely useful tool in the prevention of
      recurring VVS, even in long-term follow-up.

PMID- 22367576
TI  - Coronary atherosclerosis and a rare combination of congenital coronary anomalies
      in ST-elevation acute myocardial infarction.
AB  - A 68-year-old man with anterior ST-elevation acute myocardial infarction was
      treated with primary angioplasty of the proximal left anterior descending (LAD)
      artery. Coronary angiography showed coronary atherosclerosis and a rare
      combination of congenital coronary anomalies on other coronary vessels
      (myocardial bridge on mid-LAD and ectopic origin of the circumflex coronary).
      Coronary angioplasty on the ectopic circumflex was therefore required.

PMID- 22367577
TI  - Should raising high-density lipoprotein cholesterol be a matter of debate?
AB  - High-density lipoprotein cholesterol (HDL-C) has been identified as an
      independent inverse predictor of coronary heart disease, leading to the inclusion
      of HDL-C in certain risk engines. However, negative results also exist and create
      confusion regarding the value of interventions that increase HDL-C. The possible
      reasons for these conflicting findings are many, including not only patient
      selection (e.g. baseline HDL-C levels) but also the effect of the treatment on
      the quantity and quality of HDL. In the present review, the results of some HDL-C
      trials are discussed. They suggest that HDL-C function as well as quantity is
      clinically relevant. Furthermore, 'dysfunctional' HDL may be present in
      conditions such as diabetes or acute coronary syndromes. Efforts should focus on
      improving HDL particle functionality in addition to a numerical increase in HDL-C
      levels.

PMID- 22367578
TI  - Role of L-carnosine in the control of blood glucose, blood pressure,
      thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the
      circadian clock and histamine.
AB  - L-carnosine (beta-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal
      muscle. Although the physiological roles of CAR have not yet been clarified,
      there is evidence that the release of CAR from skeletal muscle during physical
      exercise affects autonomic neurotransmission and physiological functions. In
      particular, CAR affects the activity of sympathetic and parasympathetic nerves
      innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and
      brown adipose tissues, thereby causing changes in blood pressure, blood glucose,
      appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission
      and physiological functions were eliminated by histamine H1 or H3 receptor
      antagonists (diphenhydramine or thioperamide) and bilateral lesions of the
      hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a
      carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine
      neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released
      from skeletal muscle during exercise may be transported into TMN-histamine
      neurons and hydrolyzed. The resulting L-histidine may subsequently be converted
      into histamine, which could be responsible for the effects of CAR on
      neurotransmission and physiological function. Thus, CAR appears to influence
      hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic
      nerves and with the involvement of the SCN and histamine. These findings are
      reviewed and discussed in the context of other recent reports, including those on
      carnosine synthetases, carnosinases, and carnosine transport.

PMID- 22367579
TI  - Relative improvements in endurance performance with age: evidence from 25 years
      of Hawaii Ironman racing.
AB  - Despite of the growth of ultra-endurance sports events (of duration >6 h) over
      the previous few decades, the age-related declines in ultra-endurance performance
      have drawn little attention. The aim of the study was to analyse the changes in
      participation and performance trends of older (>40 years of age) triathletes
      between 1986 and 2010 at the Hawaii Ironman triathlon consisting of 3.8 km
      swimming, 180 km cycling and 42 km running. Swimming, cycling, running and total
      times of the best male and female triathletes between 18 and 69 years of age who
      competed in the Hawaii Ironman triathlon were analysed. The relative
      participation of master triathletes increased during the 1986-2010 period, while
      the participation of triathletes younger than 40 years of age decreased. Linear
      regression showed that males older than 44 years and females older than 40 years
      significantly improved their performances in the three disciplines and in the
      total time taken to complete the race. Gender differences in total time
      performance significantly decreased in the same time period for all age groups
      between the 40-44 and 55-59 years ones. The reasons for these relative
      improvements of Ironman athlete performances in older age groups remain, however,
      unknown. Further studies investigating training regimes, competition experience
      or sociodemographic factors are needed to gain better insights into the
      phenomenon of increasing participation and improvement of ultra-endurance
      performance with advancing age.

PMID- 22367580
TI  - Reversing T cell immunosenescence: why, who, and how.
AB  - Immunosenescence is the term commonly used to describe the multifaceted
      phenomenon encompassing all changes occurring in the immune system during aging.
      It contributes to render older adults more prone to develop infectious disease
      and main age-related diseases. While age clearly imposes drastic changes in
      immune physiology, older adults have heterogeneous health and immune phenotypes.
      This confronts scientists and researcher to develop more age-specific
      interventions rather than simply adopting intervention regimes used in younger
      people and this in order to maintain immune protection in older adults. Thus,
      this review provides evidences of the central role played by cell-mediated
      immunity in the immunosenescence process and explores the means by which
      senescent state of the cell-mediated immune function could be identified and
      predicted using biomarkers. Furthermore considerations are given to recent
      advances made in the field of age-specific immune interventions that could
      contribute to maintain immune protection, to improve quality of life, and/or to
      promote healthy aging of the growing part of the population.

PMID- 22367581
TI  - Rejuvenating activity of salidroside (SDS): dietary intake of SDS enhances the
      immune response of aged rats.
AB  - It is well known that immune response decreases with aging. Salidroside (SDS), an
      antioxidant component isolated from the traditional Chinese medicine roseroot
      Rhodiola rosea, has been demonstrated to possess potent anti-aging and health
      promoting activities. However, the mechanism underlying these activities is
      poorly understood. In this study, we clearly demonstrated that (1) dietary intake
      of SDS induced a considerable increase in total T cells (CD3(+)) and T helper
      cells (CD4(+)) in aged (21 months old) Wistar male rats; (2) SDS supplementation
      significantly increased the DTH response, a T cell-mediated immune response, in
      aged rats; and (3) SDS supplementation remarkably promoted the production of
      total anti-KLH IgG, anti-KLH IgG1, and anti-KLH IgG2alpha in aged rats without
      disturbing immune homeostasis. These indicate that SDS is able to counteract
      immunosenescence, thereby resulting in rejuvenation. Practically, SDS may be used
      to help the elderly to generate an improved response to vaccine with stronger
      humoral and cell-mediated immune responses.

PMID- 22367582
TI  - A novel homogeneous irradiation fiber probe for whole bladder wall photodynamic
      therapy.
AB  - BACKGROUND AND OBJECTIVE: We designed and fabricated a novel fiber probe that
      homogeneously illuminates the urinary bladder cavity for photodynamic therapy
      (PDT) of bladder cancer, which is known to occur in multifocal areas and to
      proliferate diffusely in the bladder mucosa. STUDY DESIGN/MATERIALS AND METHODS:
      One end of a quartz multicore fiber was twisted and conically shaped, and the
      sharpened apex of the fiber end was rounded in order to provide light of which
      the fluence distribution approximates the three-dimensional shape of the bladder
      cavity of rats. The superiority of the developed fiber probe (homogenous
      irradiation fiber probe: HIFiP) to a control fiber with a flat cleaved end (CF)
      in Photofrin(r)-PDT using a rat orthotopic bladder cancer model was evaluated.
      RESULTS: Percentage of irradiated area to the whole area of the mucosal surface
      of the bladder was 36% in the case of the CF, while it was 69% in the case of
      HIFiP (P = 0.04). A greater PDT effect was seen in rats with HIFiP-PDT, the
      volume of tumors (5.0 mm(3)) being less than half of that in the CF group (11.8
      mm(3); P = 0.02). CONCLUSIONS: HIFiP succeeded in delivering light homogenously
      to a wide area of the bladder cavity, resulting in enhancement of the PDT effect
      on bladder cancer.

PMID- 22367584
TI  - Nesfatin-1 and other hormone alterations in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is commonly characterised by obesity, insulin
      resistance (IR), hyperandrogenemia and hirsutism. Nesfatin-1 a recently
      discovered hormone, acts upon energy balance, glucose metabolism, obesity and
      probably gonadal functions. This study was to evaluate the circulating levels of
      nesfatin-1 in patients with PCOS (n = 30) and in age and body mass index (BMI)
      matched controls (n = 30). PCOS patients had significantly lower levels of
      nesfatin-1 (0.88 +/- 0.36 ng/mL) than healthy controls (2.22 +/- 1.14 ng/mL).
      PCOS patients also had higher gonadotropin and androgen plasma concentrations,
      Ferriman-Gallwey scores, blood glucose levels and a homeostasis model of
      assessment-IR index (HOMA-IR) index than in healthy women. Correlation tests in
      PCOS subjects detected a negative correlation between nesfatin-1 levels and BMI,
      fasting blood glucose, insulin levels and a HOMA-IR index. Lower nesfatin-1
      concentration may plays a very important role in the development of PCOS.

PMID- 22367583
TI  - Diagnostics and treatment of the diabetic foot.
AB  - Every 30 s, a lower limb is amputated due to diabetes. Of all amputations in
      diabetic patients 85% are preceded by a foot ulcer which subsequently
      deteriorates to a severe infection or gangrene. There is a complexity of factors
      related to healing of foot ulcers including strategies for treatment of decreased
      perfusion, oedema, pain, infection, metabolic disturbances, malnutrition, non
      weight bearing, wound treatment, foot surgery, and management of intercurrent
      disease. Patients with diabetic foot ulcer and decreased perfusion do often not
      have rest pain or claudication and as a consequence non-invasive vascular testing
      is recommended for early recognition of ulcers in need of revascularisation to
      achieve healing. A diabetic foot infection is a potentially limb-threatening
      condition. Infection is diagnosed by the presence or increased rate of signs
      inflammation. Often these signs are less marked than expected. Imaging studies
      can diagnose or better define deep, soft tissue purulent collections and are
      frequently needed to detect pathological findings in bone. The initial
      antimicrobial treatment as well as duration of treatment is empiric. There is a
      substantial delay in wound healing in diabetic foot ulcer which has been related
      to various abnormalities. Several new treatments related to these abnormalities
      have been explored in wound healing with various successes. An essential part of
      the strategy to achieve healing is an effective offloading. Many interventions
      with advanced wound management have failed due to not recognizing the need for
      effective offloading. A multidisciplinary approach to wounds and foot ulcer has
      been successfully implemented in different centres with a substantial decrease in
      amputation rate.

PMID- 22367586
TI  - Touching motion: rTMS on the human middle temporal complex interferes with
      tactile speed perception.
AB  - Brain functional and psychophysical studies have clearly demonstrated that visual
      motion perception relies on the activity of the middle temporal complex (hMT+).
      However, recent studies have shown that hMT+ seems to be also activated during
      tactile motion perception, suggesting that this visual extrastriate area is
      involved in the processing and integration of motion, irrespective of the
      sensorial modality. In the present study, we used repetitive transcranial
      magnetic stimulation (rTMS) to assess whether hMT+ plays a causal role in tactile
      motion processing. Blindfolded participants detected changes in the speed of a
      grid of tactile moving points with their finger (i.e. tactile modality). The
      experiment included three different conditions: a control condition with no TMS
      and two TMS conditions, i.e. hMT+-rTMS and posterior parietal cortex (PPC)-rTMS.
      Accuracies were significantly impaired during hMT+-rTMS but not in the other two
      conditions (No-rTMS or PPC-rTMS), moreover, thresholds for detecting speed
      changes were significantly higher in the hMT+-rTMS with respect to the control
      TMS conditions. These findings provide stronger evidence that the activity of the
      hMT+ area is involved in tactile speed processing, which may be consistent with
      the hypothesis of a supramodal role for that cortical region in motion
      processing.

PMID- 22367585
TI  - Inverse effectiveness and multisensory interactions in visual event-related
      potentials with audiovisual speech.
AB  - In recent years, it has become evident that neural responses previously
      considered to be unisensory can be modulated by sensory input from other
      modalities. In this regard, visual neural activity elicited to viewing a face is
      strongly influenced by concurrent incoming auditory information, particularly
      speech. Here, we applied an additive-factors paradigm aimed at quantifying the
      impact that auditory speech has on visual event-related potentials (ERPs)
      elicited to visual speech. These multisensory interactions were measured across
      parametrically varied stimulus salience, quantified in terms of signal to noise,
      to provide novel insights into the neural mechanisms of audiovisual speech
      perception. First, we measured a monotonic increase of the amplitude of the
      visual P1-N1-P2 ERP complex during a spoken-word recognition task with increases
      in stimulus salience. ERP component amplitudes varied directly with stimulus
      salience for visual, audiovisual, and summed unisensory recordings. Second, we
      measured changes in multisensory gain across salience levels. During audiovisual
      speech, the P1 and P1-N1 components exhibited less multisensory gain relative to
      the summed unisensory components with reduced salience, while N1-P2 amplitude
      exhibited greater multisensory gain as salience was reduced, consistent with the
      principle of inverse effectiveness. The amplitude interactions were correlated
      with behavioral measures of multisensory gain across salience levels as measured
      by response times, suggesting that change in multisensory gain associated with
      unisensory salience modulations reflects an increased efficiency of visual speech
      processing.

PMID- 22367587
TI  - Possible action of vasohibin-1 as an inhibitor in the regulation of
      vascularization of the bovine corpus luteum.
AB  - The development of the corpus luteum (CL), which secretes large amounts of
      progesterone to establish pregnancy, is accompanied by active angiogenesis,
      vascularization, and lymphangiogenesis. Negative feedback regulation is a
      critical physiological mechanism. Vasohibin-1 (VASH1) was recently discovered as
      a novel endothelium-derived negative feedback regulator of vascularization. We
      therefore investigated the expression of VASH1 in the bovine CL. Expression of
      VASH1 mRNA and protein was predominantly localized to luteal endothelial cells
      (LECs). VASH1 expression in the CL was constant through the early to late luteal
      phases and decreased during CL regression relating with the action of luteolytic
      prostaglandin F(2)(alpha) in vivo. To investigate the role of VASH1, we
      determined whether VASH1 treatment affects angiogenesis and/or lymphangiogenesis
      using LECs and lymphatic endothelial cells (LyECs) in vitro. Vascular endothelial
      growth factor A (VEGFA) stimulated the expression of VASH1 in LECs but not in
      LyECs, and VASH1 completely blocked VEGFA-induced formation of capillary-like
      tube structures of LECs and LyECs in vitro. In summary, VASH1 is predominantly
      located on LECs in the bovine CL and inhibits the angiogenic and lymphangiogenic
      actions of VEGFA. Bovine CL therefore has a VEGFA-VASH1 system that may be
      involved in regulation of luteal function, especially in the development of the
      CL. The results indicate that VASH1 has the potential to act as a negative
      feedback regulator of angiogenesis and lymphangiogenesis in the CL in cows.

PMID- 22367588
TI  - Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes
      of pituitary-specific Esr1 knockout female mice.
AB  - Estrogen receptor 1 and 2 (ESR1 and 2) mediate estrogen (E) action on gonadotrope
      function. While much is known about the effects of ESR1 on the gonadotrope, there
      is still some controversy regarding the effects of ESR2. To investigate the role
      of ESR2 in the gonadotrope, 45-day-old female mice of two different genotypes
      were used: wild type (WT) and pituitary (gonadotropes and thyrotropes)-specific
      Esr1 knockout (KO). All mice were ovariectomized (OVX) and 15 days later injected
      over 3 days with 2.5 MUg 17beta-estradiol (E(2)), 0.2 mg of the selective ESR1 or
      2 agonists, propylpyrazole triol and diarylpropionitrile, respectively, or 0.1 ml
      oil. The day after treatment, anterior pituitary glands were dissected out for
      evaluation of gonadotrope ultrastructural morphology and pituitary
      immunohistochemical expression of progesterone receptor (Pgr (Pr)). Blood was
      collected and serum LH levels were assessed. Activation of ESR1 in WT mice
      resulted in the following: i) uterine ballooning and vaginal cornification, ii)
      negative feedback on LH secretion, iii) increased number of homogeneous
      (functional) gonadotropes, and iv) pituitary Pgr expression (35.9+/-2.0% of
      pituitary cells). Activation of ESR1 in KO mice induced normal uterine, vaginal,
      and LH secretion responses, but failed to increase the number of functional
      gonadotropes, and induced significantly lower Pgr expression (21.0+/-3.0% of
      pituitary cells) than in WT mice. Whilst activation of ESR2 had no significant
      effects in WT mice, it doubled the number of functional gonadotropes exhibited by
      KO mice injected with oil. It is concluded that E(2) exerted its action in KO
      mouse gonadotropes via ESR2.

PMID- 22367590
TI  - Effect of ectopic expression of homeoprotein EGAM1C on the cell morphology,
      growth, and differentiation in a mouse embryonic stem cell line, MG1.19 cells.
AB  - The homeoprotein EGAM1C was identified in preimplantation mouse embryos and
      embryonic stem (ES) cells. To explore the impact of EGAM1C on the hallmarks of
      mouse ES cells, MG1.19 cells stably expressing EGAM1C at levels similar to those
      in blastocysts were established using an episomal expression system. In the
      presence of leukemia inhibitory factor (+LIF), control transfectants with an
      empty vector formed flattened cell colonies, while Egam1c transfectants formed
      compacted colonies with increased E-CADHERIN expression. In Egam1c transfectants,
      the cellular contents of POU5F1 (OCT4), SOX2, TBX3, and NANOG increased. Cell
      growth was accelerated in an undifferentiated state sustained by LIF and in the
      course of differentiation. During clonal proliferation, EGAM1C stabilized the
      undifferentiated state. In adherent culture conditions, EGAM1C partly inhibited
      the progression of differentiation at least within a 4-day culture period in the
      presence of retinoic acid by preventing the downregulation of LIF signaling with
      a robust increase in TBX3 expression. Conversely, EGAM1C enhanced the expression
      of lineage marker genes Fgf5 (epiblast), T (mesoderm), Gata6 (primitive
      endoderm), and Cdx2 (trophectoderm) in -LIF conditions. In embryoid bodies
      expressing EGAM1C, the expression of marker genes for extraembryonic cell
      lineages, including Tpbpa (spongiotrophoblast) and Plat (parietal endoderm),
      increased. These results demonstrated that the ectopic expression of EGAM1C is
      capable of affecting the stabilization of an undifferentiated state and the
      progression of differentiation in MG1.19 ES cells, in addition to affecting
      cellular morphology and growth.

PMID- 22367589
TI  - Effect of follicular aspiration just before ovulation on corpus luteum
      characteristics, circulating progesterone concentrations and uterine receptivity
      in single-ovulating and superstimulated heifers.
AB  - The aim of this study was to investigate, in unstimulated and superstimulated
      heifers, the effect of follicle aspiration just before ovulation on corpus luteum
      (CL) development, circulating progesterone (P(4)) concentrations and the ability
      of the uterus to support embryo development. Following follicle aspiration or
      ovulation timed from GNRH administration, CL development was assessed by daily
      ultrasonography, and CL function was assessed in terms of the capacity to produce
      P(4) and the expression of genes involved in steroidogenesis in luteal tissue.
      The capacity of the uterine environment to support conceptus development was
      assessed following transfer and recovery of in vitro-produced embryos. Follicular
      aspiration just before the expected time of ovulation leads to a significant
      reduction in CL diameter, CL area and area of luteal tissue. This was associated
      with a decrease in circulating P(4) in both unstimulated and superstimulated
      heifers. Follicle aspiration leads to a reduction in conceptus length and area on
      day 14 in unstimulated heifers only. Follicle aspiration leads to a reduction in
      the expression of LHCGR in luteal tissue from unstimulated heifers compared with
      those in which the CL formed after ovulation. Superstimulation significantly
      reduced the expression of STAR in luteal tissue in both ovulated and follicle
      aspirated heifers. In conclusion, in stimulated and unstimulated heifers,
      aspiration of the preovulatory dominant follicle(s) just before expected
      ovulation interferes with the subsequent formation and function of the CL, in
      terms of size and P(4) output and this, in turn, is associated with a reduced
      capacity of the uterus to support conceptus elongation in unstimulated heifers.

PMID- 22367591
TI  - Stimulation of Sertoli cell proliferation: defining the response interval to an
      inhibitor of estrogen synthesis in the boar.
AB  - Sertoli cell proliferation occurs in two major waves after birth, one neonatally
      and another prepubertally, each contributing to final testicular size and sperm
      production. However, little is known about the regulation of either wave. We have
      previously shown that letrozole, an inhibitor of estrogen synthesis, increases
      Sertoli cell number and testicular size at sexual maturity in boars. These
      studies were conducted to determine whether letrozole affects the first or second
      proliferative wave. Boars were treated with letrozole during the first wave
      (treatment at 1, 3, and 5 weeks), less frequently (1 week of age only, or 1 and 5
      weeks), on postnatal day 1, or during the second wave (weeks 11-16). Sertoli
      cells were enumerated in testes and estrogen concentrations were evaluated in
      serum and testes. Compared with vehicle controls, letrozole reduced estrogen in
      boars treated at weeks 1 and 5 or 1, 3, and 5, on postnatal day 1, or
      prepubertally. However, Sertoli cell numbers were increased only in boars treated
      at 1, 3, and 5 weeks of age. Neither perinatal (1 day old) nor prepubertal
      letrozole treatment affected Sertoli cell numbers. Hence, Sertoli cell
      proliferation was sensitive to letrozole only if letrozole was administered
      throughout the first wave, even though estrogen synthesis was effectively
      inhibited at all ages. These data indicate that the neonatal but not the
      prepubertal window of Sertoli cell proliferation is sensitive to an inhibitor of
      estrogen synthesis; this suggests that these two waves are differently regulated.

PMID- 22367592
TI  - Implementing cancer prevention into clinical practice.
AB  - Cancer prevention has been associated with decreased rates of cancer incidence
      and increased survival. Cancer prevention, however, can have a greater impact if
      barriers to implementing cancer prevention into practice are removed and
      opportunities are both fostered and seized. The purpose of this article is to
      identify barriers and opportunities to cancer prevention in clinical practice and
      provide recommendations for the future. A multidisciplinary team participated in
      "The Future Directions Cancer Prevention and Control: Workforce Implications for
      Training, Practice and Policy" workshop on October 17-18, 2009 at The University
      of Texas MD Anderson Cancer Center in Houston, TX. During the meeting, the team
      discussed barriers and opportunities for the implementation of cancer prevention
      into clinical practice. Further data were collected from peer-reviewed journals
      and published government and cancer agencies reports. Several issues were
      identified: (1) The funding allocated to basic cancer prevention research and
      application is not optimal and less than that for cancer treatment; (2)
      participation in cancer prevention behaviors and screening practices are lower
      than desired, especially among the uninsured; (3) a shortage in healthcare
      professionals is a major challenge in meeting the future needs of cancer
      prevention; (4) demands on medical schools to balance increased enrollment,
      incorporate cancer prevention in an already crowded curriculum, and develop
      faculty are daunting; and (5) healthcare reforms in 2010 provide both
      opportunities and additional challenges for cancer prevention. Based on the
      current state of cancer prevention, we formed six recommendations: (1) additional
      funding for cancer prevention research with a focus on implementation into
      practice, (2) improved tracking of cancer prevention research funding and the
      outcomes associated with it, (3) continued monitoring of cancer prevention
      services participation with emphasis on closing the gap in health disparities,
      (4) financial and technical assistance to healthcare professional schools for
      incorporating cancer prevention into curricula, (5) assessment of the current
      state of technology in cancer prevention care, and (6) the use of effective
      multidisciplinary teams in cancer prevention care. Improved delivery of cancer
      prevention services can have a tremendous impact on cancer incidence and survival
      rates.

PMID- 22367593
TI  - Addressing the future burden of cancer and its impact on the oncology workforce:
      where is cancer prevention and control?
AB  - The need for cancer professionals has never been more urgent than it is today.
      Reports project serious shortages by 2020 of oncology health care providers.
      Although many plans have been proposed, no role for prevention has been
      described. In response, a 2-day symposium was held in 2009 at The University of
      Texas MD Anderson Cancer Center to capture the current status of the cancer
      prevention workforce and begin to identify gaps in the workforce. Five working
      groups were organized around the following topic areas: (a) health policy and
      advocacy; (b) translation to the community; (c) integrating cancer prevention
      into clinical practice; (d) health services infrastructure and economics; and (e)
      discovery, research, and technology. Along with specific recommendations on these
      topics, the working groups identified two additional major themes: the difficulty
      of defining areas within the field (including barriers to communication) and lack
      of sufficient funding. These interdependent issues synergistically impede
      progress in preventing cancer; they are explored in detail in this synthesis, and
      recommendations for actions to address them are presented. Progress in cancer
      prevention should be a major national and international goal. To achieve this
      goal, ensuring the health of the workforce in cancer prevention and control is
      imperative.

PMID- 22367594
TI  - Ca(2+)-binding reduces conformational flexibility of RC-LH1 core complex from
      thermophile Thermochromatium tepidum.
AB  - The light-harvesting complex, LH1, of thermophile purple bacteria
      Thermochromatium tepidum consists of an array of alpha- and beta-polypeptides
      which assemble the photoactive bacteriochlorophyll and closely interact with the
      membrane-lipids. In this study, we investigated the effect of calcium and
      manganese ions on the protein structure and thermostability of the reaction
      centre (RC)-LH1/lipid complex. The binding of Ca(2+), but not Mn(2+) is shown to
      shift the LH1 Q ( y ) absorption maximum from ~889 to 915 nm and to significantly
      raise the thermostability of the RC-LH1 complex. The ATR-FTIR spectra indicate
      that interaction of Ca(2+) as monitored by the carboxylates' vibration of
      aspartate residues, but not Mn(2+) induces changes in the alpha-helix packing
      arrangement. The reduced rate of (1)H/(2)H exchange of proteins' amide protons
      shows that the accessibility to (2)H(2)O is significantly lowered in Ca(2+)
      substituted RC-LH1/lipid complexes. In particular, exchange with the associated
      lipid molecules, is significantly retarded. These results suggest that the
      thermostability of the RC-LH1 complex is raised by the distinct interaction with
      calcium cations which reduces the RC-LH1/lipid dynamics, particularly, at the
      membrane-water interface.

PMID- 22367595
TI  - Endovascular therapy for vasculogenic erectile dysfunction.
AB  - OPINION STATEMENT: Erectile dysfunction (ED) is an important clinical condition
      that affects a significant proportion of men. Although there are many etiologies
      for ED, many cases have a vascular basis that is related to inadequate arterial
      inflow, veno-occlusive dysfunction, or abnormalities in smooth muscle (cavernosal
      tissue) relaxation. These vascular abnormalities can exist in isolation or
      combination. Since the advent of phosphodiesterase-5 inhibitor (PDE5i) therapy,
      the initial management of ED in most cases consists of a brief medical evaluation
      followed by a trial of PDE5i therapy. However, up to 50% of men have an
      inadequate response to PDE5i therapy and discontinue therapy. Subsequent
      therapies for ED are increasingly invasive, including penile injection of
      vasodilators, vacuum pumps, and penile implants. With increased awareness of ED
      among clinicians and the growing mechanistic link between ED and atherosclerotic
      vascular disease, there has been renewed interest in the diagnosis and management
      of arteriogenic ED. Prior reports in the 1980s described the existence of
      arterial inflow lesions in patients with ED, and there are a modest number of
      reports describing the feasibility of revascularization with balloon angioplasty.
      Despite initial clinical success, enthusiasm for this technique waned, presumably
      because ED frequently recurred due to restenosis and lack of small vessel
      endovascular therapies. Recent investigation and the availability of newer tools
      such as drug-eluting stents have renewed interest in this field. Although
      conceptually attractive, endovascular therapy for ED presents significant
      challenges related to unanswered questions such as the prevalence and appropriate
      diagnostic evaluation of arteriogenic ED, and the safety and feasibility of stent
      based therapies in this population. In addition, the evaluation, management, and
      follow-up of patients with vascular ED require a multi-disciplinary team with
      specialists in urology, sexual medicine, and vascular medicine. Despite these
      challenges, the potential for endovascular treatment of these patients remains
      one of the most exciting areas of investigation in vascular medicine.

PMID- 22367596
TI  - Oxymatrine attenuates bleomycin-induced pulmonary fibrosis in mice via the
      inhibition of inducible nitric oxide synthase expression and the TGF-beta/Smad
      signaling pathway.
AB  - Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora flavescens
      Ait. with a variety of pharmacological activities. The aim of this study was to
      investigate the preventive effects of OM on bleomycin (BLM)-induced pulmonary
      fibrosis (PF) and to further explore the underlying mechanisms. C57BL/6 mice were
      randomly assigned to five groups: the saline sham group; the BLM group, in which
      mice were endotracheally instilled with BLM (3.0 mg/kg); and the BLM plus OM
      groups, in which OM was given to mice daily (10, 20 or 40 mg/kg) one day after
      BLM instillation for 21 days. The bronchoalveolar lavage fluid (BALF) and lung
      tissues were collected at 15 and 22 days post BLM administration, respectively.
      Lung tissues were stained with hematoxylin and eosin (H&E) for histological
      evaluation. Levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and
      nitric oxide (NO) in mouse BALF were measured, as well as myeloperoxidase (MPO)
      activity and malondialdehyde (MDA) content in lung homogenates. The inducible
      nitric oxide synthase (iNOS) expression in the lung tissues was determined by
      immunohistochemical staining, quantitative real-time PCR and western blot
      analysis. Moreover, the expression of transforming growth factor (TGF)-beta1,
      Smad2, Smad3, p-Smad2 and p-Smad3 were also detected. We found that OM improved
      BLM-induced lung pathological changes, inhibited MPO activity and reduced MDA
      levels in a dose-dependent manner. OM also dose-dependently inhibited the release
      of TNF-alpha and IL-6, and decreased the expression of iNOS in lung tissues and
      thus prevented NO release in response to BLM challenge. In addition, OM decreased
      the expression of TGF-beta1, p-Smad2 and p-Smad3, which are all important members
      of the TGF-beta/Smad signaling pathway. Our study provides evidence that OM
      significantly ameliorated BLM-induced PF in mice via the inhibition of iNOS
      expression and the TGF-beta/Smad pathway.

PMID- 22367597
TI  - Serum amyloid A levels associated with gastrointestinal manifestations in Henoch
      Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is considered as an immune-mediated inflammatory
      disease. Serum amyloid A (SAA) is an acute-phase protein with proinflammatory
      effects. We investigated the levels of SAA in HSP patients and examined whether
      SAA levels are associated with organ involvement and disease severity. Seventy
      patients with HSP, including 35 with nephritis (HSPN) and 35 without HSPN, and 20
      controls were recruited in our study. SAA levels were measured and other clinical
      laboratory parameters, including C-reactive protein, erythrocyte sedimentation
      rate, complement 3 (C3), C4, and immunoglobulin (Ig) A, were recorded. SAA levels
      were not found to be independently associated with renal, joint involvement, and
      disease severity. However, higher SAA levels were observed in HSP patients with
      gastrointestinal (GI) manifestations (p=0.006, p (c)=0.048). Moreover, the levels
      of SAA were significantly associated with duration of disease (p<0.005,
      p(c)<0.04). Our findings suggested that SAA was significantly associated with
      disease duration and GI manifestations in HSP patients.

PMID- 22367598
TI  - Fructose-1,6-bisphosphate reduces the mortality in Candida albicans bloodstream
      infection and prevents the septic-induced platelet decrease.
AB  - Due to the fact that an increased number of patients have experienced bloodstream
      infections caused by Candida species and the high mortality of this infection,
      there is a need for a strategy to reduce this scenery. One possible strategy is
      the use of new drugs, such as fructose-1,6-bisphosphate (FBP), which is a high
      energy glycolytic metabolite and has shown to have therapeutic effects in several
      pathological conditions such as ischemia, shock, toxic injuries, and bacterial
      sepsis. The aim of this manuscript was to determine the role of FBP in
      experimental Candida albicans bloodstream infection. We used mice that were
      divided into three experimental groups: sham (not induced), bloodstream infection
      (induced with intratracheal instillation of C. albicans) and FBP (bloodstream
      infection plus FBP 500 mg/kg i.p.). Blood was taken for assessment of complete
      hematological profile and cytokine assay (IL-6 and MCP-1). Results of the study
      demonstrated that mortality decreased significantly in groups that received FBP.
      All cytokine and hematological indexes of FBP group were similar to bloodstream
      infection group with exception of platelets count. FBP significantly prevented
      the decrease in platelets. Taken together, our results demonstrate that FBP
      prevented the mortality in C. albicans bloodstream infection.

PMID- 22367600
TI  - Coping with abundance: the burden of progress in medical oncology.

PMID- 22367599
TI  - Effect of hochuekkito on alveolar macrophage inflammatory responses in
      hyperglycemic mice.
AB  - Diabetes mellitus reduces immunological activity and increases susceptibility to
      various infections. Hochuekkito (TJ-41) has been reported to improve the weakened
      physical condition of various chronic diseases. BALB/c mice were divided into
      three groups; groups A and B were fed a standard diet, and group C, a TJ-41 diet.
      Two weeks after starting these diets, hyperglycemia was induced in groups B and C
      by injection with streptozotocin. Two weeks later, bronchoalveolar lavage was
      performed. Toll-like receptor (TLR) ligands (TLR2: peptidoglycan, PGN; TLR4:
      lipopolysaccharide, LPS; TLR5: flagellin, FLG) were used to stimulate alveolar
      macrophages (AMs), and TNF-alpha production was measured. Under hyperglycemic
      conditions and PGN or FLG stimulation, TNF-alpha production from AMs was
      significantly reduced in group B compared with group A. However, treatment with
      TJ-41 (group C) significantly improved the impaired production of TNF-alpha.
      These results suggest that, under hyperglycemic conditions, TJ-41 can improve the
      inflammatory responses of AMs with stimulation of TLR ligands.

PMID- 22367602
TI  - Effect of salt on the compression of polyelectrolyte brushes in a theta solvent.
AB  - Classical strong-stretching theory (SST) predicts that, as opposing
      polyelectrolyte brushes are compressed together in a salt-free theta solvent,
      they contract so as to maintain a finite polymer-free gap, which offers a
      potential explanation for the ultra-low frictional forces observed in experiments
      despite the application of large normal forces. However, the SST ignores chain
      fluctuations, which would tend to close the gap resulting in physical contact and
      in turn significant friction. In a preceding study, we examined the effect of
      fluctuations using self-consistent field theory (SCFT) and illustrated that high
      normal forces can still be applied before the gap is destroyed. We now look at
      the effect of adding salt. It is found to reduce the long-range interaction
      between the brushes but has little effect on the short-range part, provided the
      concentration does not enter the salted-brush regime. Consequently, the maximum
      normal force between two planar brushes at the point of contact is remarkably
      unaffected by salt. For the crossed-cylinder geometry commonly used in
      experiments, however, there is a gradual reduction because in this case the long
      range part of the interaction contributes to the maximum normal force.

PMID- 22367603
TI  - Biaxial nematic phase in the Maier-Saupe model for a mixture of discs and
      cylinders.
AB  - We analyze the global phase diagram of a Maier-Saupe lattice model with the
      inclusion of shape-disordered degrees of freedom to mimic a mixture of oblate and
      prolate molecules (discs and cylinders). In the neighborhood of a Landau
      multicritical point, solutions of the statistical problem can be written as a
      Landau-de Gennes expansion for the free energy. If the shape-disordered degrees
      of freedom are quenched, we confirm the existence of a biaxial nematic structure.
      If orientational and disorder degrees of freedom are allowed to thermalize, this
      biaxial solution becomes thermodynamically unstable. Also, we use a two
      temperature formalism to mimic the presence of two distinct relaxation times, and
      show that a slight departure from complete thermalization is enough to stabilize
      a biaxial nematic phase.

PMID- 22367604
TI  - White matter and deep gray matter hemodynamic changes in multiple sclerosis
      patients with clinically isolated syndrome.
AB  - The dynamic susceptibility contrast magnetic resonance imaging perfusion
      technique was used to investigate possible hemodynamic changes in normal
      appearing white matter and deep gray matter (DGM) of 30 patients with clinically
      isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple
      sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood
      volume, cerebral blood flow (CBF), and mean transit time values were estimated.
      Normalization was achieved for each subject with respect to average values of CBF
      and mean transit time of the hippocampi's dentate gyrus. Measurements concerned
      three regions of normal white matter of normal volunteers, normal appearing white
      matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM
      regions, bilaterally. All measured normal appearing white matter and DGM regions
      of the patients with CIS had significantly higher cerebral blood volume and mean
      transit time values, while averaged DGM regions had significantly lower CBF
      values, compared to those of normal volunteers (P < 0.001). Regarding patients
      with relapsing-remitting multiple sclerosis, all measured normal appearing white
      matter and DGM regions showed lower CBF values than those of normal volunteers
      and lower cerebral blood volume and CBF values compared to patients with CIS (P <
      0.001). These data provide strong evidence that hemodynamic changes--affecting
      both white and DGM--may occur even at the earliest stage of multiple sclerosis,
      with CIS patients being significantly different than relapsing-remitting multiple
      sclerosis patients.

PMID- 22367605
TI  - The endocannabinoid system: a revolving plate in neuro-immune interaction in
      health and disease.
AB  - Studies of the last 40 years have brought to light an important physiological
      network, the endocannabinoid system. Endogenous and exogenous cannabinoids
      mediate their effects through activation of specific cannabinoid receptors. This
      modulatory homoeostatic system operates in the regulation of brain function and
      also in the periphery. The cannabinoid system has been shown to be involved in
      regulating the immune system. Studies examining the effect of cannabinoid-based
      drugs on immunity have shown that many cellular and cytokine mechanisms are
      modulated by these agents, thus raising the hypothesis that these compounds may
      be of value in the management of chronic inflammatory diseases. The special
      properties of endocannabinoids as neurotransmitters, their pleiotropic effects
      and the impact on immune function show that the endocannabinoid system represents
      a revolving plate of neural and immune interactions. In this paper, we outline
      current information on immune effects of cannabinoids in health and disease.

PMID- 22367606
TI  - Student objectives and learning experiences in a global health elective.
AB  - International health electives offer unique experiences for medical students to
      develop clinical skills and cultural competencies in unique and diverse
      environments. Medical students have been increasingly pursuing these learning
      opportunities despite the challenges. However, their goals in pursuing these
      opportunities and the relation between their learning objectives and actual
      experiences have not been studied adequately. It is important to assess these
      programs based on student objectives and whether those objectives are met. Thirty
      seven medical students from five cohorts at a US medical school completed pre
      post questionnaires regarding their global health elective objectives and
      learning experiences. The questionnaires included mostly open-ended questions and
      a Likert-scale rating of their overall experience. Qualitative thematic analysis
      involved inductive coding and followed a content-driven immersion-crystallization
      approach. Quantitative program evaluation measures yielded descriptive
      statistics. Five general objectives and four types of learning experiences were
      identified. Student objectives were: (1) to observe the practice and organization
      of health care in another country; (2) improve medical/surgical skills; (3)
      improve language skills; (4) learn about another culture; and (5) deepen
      knowledge of infectious diseases. All of their objectives were achieved.
      Moreover, one learning theme, "self-reflection and personal growth," was not a
      student objective. Quantitative assessment showed that most students had a
      favorable elective experience. Program challenges were also identified. Students
      in a global health elective were able to fulfill self-identified learning
      objectives, while also gaining other unexpected yet important lessons. Students'
      learning objectives also should be considered in evaluating learning experiences
      in international health electives.

PMID- 22367607
TI  - Energy drink use and adverse effects among emergency department patients.
AB  - Energy drink usage is common and contains caffeine or other stimulants. We
      evaluated demographics, prevalence, reasons and adverse effects with consuming
      energy beverages. Cross-sectional study of a convenience sample of patients
      recruited from two San Diego Emergency Departments from January to December 2009.
      One-thousand-two-hundred-ninety-eight subjects participated of which 52.6% were
      male. Ethnicity: Caucasian 48.3%, African American 17%, Hispanic 18%, Other
      16.7%. Age ranges: 18-29 years (38.4%), 30-54 years (49.6%) and greater than 55
      years (12%). Reasons for use: 57% to "increase energy", 9.5% for studying/work
      projects, 2.4% while prolonged driving, improve sports performance 2%, with
      ethanol 6.3%, "other" reasons 22.1%. Adverse reactions reported by 33.5% (429)
      patients. Two-hundred-eighty report feeling "shaky/jittery", insomnia 136,
      palpitations 150, gastrointestinal upset 82, headache 68, chest pain 39, and
      seizures in 6. Eighty-five patients reported co-ingestion with illicit
      "stimulants" including cocaine and methamphetamine. We identified one-third of
      patients reported at least one adverse effect. Whilst most were not severe, a
      small number were serious e.g., seizures. In addition, some report purposely
      ingesting with illicit drugs.

PMID- 22367608
TI  - Human papillomavirus genotype detection in recurrent respiratory papillomatosis
      (RRP) in Colombia.
AB  - BACKGROUND: Knowledge on human papillomavirus (HPV) genotype distribution in
      recurrent respiratory papillomatosis (RRP) is essential to assess the impact of
      HPV vaccine. It is provided information for Colombia. METHODS: In all, 189 RRP
      primary cases diagnosed between 1985 and 2009 were identified from 5 pathology
      laboratories of Cali and Medellin, Colombia. HPV DNA testing in 129 cases that
      fulfilled inclusion criteria (available paraffin blocks, amplifiable DNA, and
      confirmed histologic diagnosis of RRP) was performed by the SPF-10/LiPA25 assay
      (version 1). RESULTS: Of all cases 36.1% were juvenile (<12 years old) and a
      majority of adults were males (p = .09); 95% of cases were HPV positive. HPV 6,
      11, and 16 contributed to 69%, 27.1%, and 7.8% of all HPV positive cases. Twelve
      cases (9.3%) showed multiple infections; 8 of these were HPV 6 or 11 positive.
      CONCLUSIONS: HPV prophylactic vaccine including HPV 6 and 11 may have a major
      impact against RRP.

PMID- 22367609
TI  - The use of a "mystery shopper" methodology to evaluate children's access to
      psychiatric services.

PMID- 22367610
TI  - Understanding the mechanistic roles of 30Kc6 gene in apoptosis and specific
      productivity in antibody-producing Chinese hamster ovary cells.
AB  - Previously, we reported that the expression of Bombyx mori 30Kc6 gene in Chinese
      hamster ovary (CHO) cells increases recombinant protein production by both
      inhibiting apoptosis and enhancing specific productivity. In this study, in order
      to gain a thorough understanding of the roles of 30Kc6 gene in antibody
      production, the mechanisms modulating cell apoptosis and specific productivity
      were investigated. 30Kc6 gene was introduced into a CHO cell line producing a
      chimeric anti-human CD20 monoclonal antibody. The stable expression of 30Kc6
      increased cell viability and productivity by 46.7% and 3.4-folds, respectively.
      It was observed that the Bax translocation from cytosol to mitochondria and the
      cytochrome c (cyt c) release from mitochondrial intermembrane space to cytosol
      were repressed, which resulted in a decrease in the activation of apoptosis
      executioner, caspase-3. On the other hand, 30Kc6 expression increased the
      specific productivity by 2.3-folds. However, at the transcription level, the
      relative levels of heavy and light chain mRNAs increased only by 8.3% and 8.7%,
      respectively, which was not accountable for the observed increment in the
      specific productivity. Instead, the mitochondrial membrane potential was
      maintained and the ATP generation was stimulated. A higher ATP level could
      activate the mammalian target of rapamycin (mTOR), which drives the translation
      initiation and elongation by phosphorylating eukaryotic initiation factor 4E
      binding protein 1 (4EBP1) and S6 kinase 1 (S6K1). In the 30Kc6-expressing cells,
      both the 4EBP1 and S6K1 were phosphorylated at higher levels, which indicated
      that the increased specific productivity primarily resulted from the boost of
      translation process. Furthermore, it was also found that the specific uptake
      rates of glucose and glutamine were not affected by 30Kc6 expression,
      demonstrating that the enhanced ATP generation and consequently maintained mTOR
      activity were due to 30Kc6 expression but not the different metabolic uptake
      rates. In conclusion, 30Kc6 expression inhibited apoptosis by repressing the Bax
      translocation, which down-regulated the downstream cascade responses including
      cyt c release and caspase-3 activation. Also, 30Kc6 expression increased the
      specific productivity by enhancing the translation process.

PMID- 22367611
TI  - Physiological characterization of recombinant Saccharomyces cerevisiae expressing
      the Aspergillus nidulans phosphoketolase pathway: validation of activity through
      13C-based metabolic flux analysis.
AB  - Several bacterial species and filamentous fungi utilize the phosphoketolase
      pathway (PHK) for glucose dissimilation as an alternative to the Embden-Meyerhof
      Parnas pathway. In Aspergillus nidulans, the utilization of this metabolic
      pathway leads to increased carbon flow towards acetate and acetyl CoA. In the
      first step of the PHK, the pentose phosphate pathway intermediate xylulose-5
      phosphate is converted into acetylphosphate and glyceraldehyde-3-phosphate
      through the action of xylulose-5-phosphate phosphoketolase, and successively
      acetylphosphate is converted into acetate by the action of acetate kinase. In the
      present work, we describe a metabolic engineering strategy used to express the
      fungal genes of the phosphoketolase pathway in Saccharomyces cerevisiae and the
      effects of the expression of this recombinant route in yeast. The phenotype of
      the engineered yeast strain MP003 was studied during batch and chemostat
      cultivations, showing a reduced biomass yield and an increased acetate yield
      during batch cultures. To establish whether the observed effects in the
      recombinant strain MP003 were due directly or indirectly to the expression of the
      phosphoketolase pathway, we resolved the intracellular flux distribution based on
      (13)C labeling during chemostat cultivations. From flux analysis it is possible
      to conclude that yeast is able to use the recombinant pathway. Our work indicates
      that the utilization of the phosphoketolase pathway does not interfere with
      glucose assimilation through the Embden-Meyerhof-Parnas pathway and that the
      expression of this route can contribute to increase the acetyl CoA supply,
      therefore holding potential for future metabolic engineering strategies having
      acetyl CoA as precursor for the biosynthesis of industrially relevant compounds.

PMID- 22367612
TI  - Transcription analysis of hyaluronan biosynthesis genes in Streptococcus
      zooepidemicus and metabolically engineered Lactococcus lactis.
AB  - The has operon genes in the hyaluronan (HA) producer, Streptococcus
      zooepidemicus, encode for some of the critical enzymes in the HA biosynthetic
      pathway. Heterologous expression of different combinations of multiple has genes
      has resulted in increasing HA production to varying degrees in different
      recombinant strains. In this work, a recombinant Lactococcus lactis strain (SJR6)
      was constructed, with insertion of three has operon genes (hasABD) from S.
      zooepidemicus. The SJR6 strain was found to be a better HA producer than two
      previously constructed recombinant L. lactis strains (SJR2 and SJR3), containing
      hasAB and hasABC genes, respectively, but exhibited lower HA production than the
      native HA producer S. zooepidemicus. To understand the differences in HA yield
      between the various strains, transcriptions of the HA biosynthesis genes (has
      genes and their homologues) were compared at different phases of exponential
      growth of the L. lactis and S. zooepidemicus cultures. The mRNA levels of all the
      heterologous has genes were expectedly far higher than their corresponding
      homologues in the L. lactis strains. The relative mRNA level of the hasB
      homologue, viz. ugd (encoding UDP-glucose dehydrogenase), was found to be much
      lower than that of other homologues, corroborating earlier reports which indicate
      tight transcriptional regulation of the ugd gene in L. lactis. Interestingly, all
      the has gene homologues were found to be up-regulated in all the recombinant L.
      lactis strains, when compared with the corresponding genes in the untransformed
      strain, L. lactis NZ9000. A transcription analysis of S. zooepidemicus cultures
      revealed that the has operon was down-regulated in the mid-exponential growth
      phase in comparison to the early- and late-exponential growth phases. The
      transcription analyses in this study have provided insights for the design of
      recombinant strains with higher HA productivity.

PMID- 22367613
TI  - Functionality of the TOL plasmid under varying environmental conditions following
      conjugal transfer.
AB  - Conjugation of catabolic plasmids in contaminated environments is a naturally
      occurring horizontal gene transfer phenomenon, which could be utilized in genetic
      bioaugmentation. The potentially important parameters for genetic bioaugmentation
      include gene regulation of transferred catabolic plasmids that may be controlled
      by the genetic characteristics of transconjugants as well as environmental
      conditions that may alter the expression of the contaminant-degrading phenotype.
      This study showed that both genomic guanine-cytosine contents and phylogenetic
      characteristics of transconjugants were important in controlling the phenotype
      functionality of the TOL plasmid. These genetic characteristics had no apparent
      impact on the stability of the TOL plasmid, which was observed to be highly
      variable among strains. Within the environmental conditions tested, the addition
      of glucose resulted in the largest enhancement of the activities of enzymes
      encoded by the TOL plasmid in all transconjugant strains. Glucose (1 g/L)
      enhanced the phenotype functionality by up to 16.4 (+/-2.22), 30.8 (+/-7.03), and
      90.8 (+/-4.56)-fold in toluene degradation rates, catechol 2,3-dioxygenase
      enzymatic activities, and xylE gene expression, respectively. These results
      suggest that genetic limitations of the expression of horizontally acquired genes
      may be overcome by the presence of alternate carbon substrates. Such observations
      may be utilized in improving the effectiveness of genetic bioaugmentation.

PMID- 22367614
TI  - Differential degradation of full-length and cleaved ataxin-7 fragments in a novel
      stable inducible SCA7 model.
AB  - Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders
      caused by expanded polyglutamine repeats, and a common toxic gain-of-function
      mechanism has been proposed. Proteolytic cleavage of several polyglutamine
      proteins has been identified and suggested to modulate the polyglutamine
      toxicity. In this study, we show that full-length and cleaved fragments of the
      SCA7 disease protein ataxin-7 (ATXN7) are differentially degraded. We found that
      the ubiquitin-proteosome system (UPS) was essential for the degradation of full
      length endogenous ATXN7 or transgenic full-length ATXN7 with a normal or expanded
      glutamine repeat in both HEK 293T and stable PC12 cells. However, a similar
      contribution by UPS and autophagy was found for the degradation of
      proteolytically cleaved ATXN7 fragments. Furthermore, in our novel stable
      inducible PC12 model, induction of mutant ATXN7 expression resulted in toxicity
      and this toxicity was worsened by inhibition of either UPS or autophagy. In
      contrast, pharmacological activation of autophagy could ameliorate the ATXN7
      induced toxicity. Based on our findings, we propose that both UPS and autophagy
      are important for the reduction of mutant ataxin-7-induced toxicity, and
      enhancing ATXN7 clearance through autophagy could be used as a potential
      therapeutic strategy in SCA7.

PMID- 22367616
TI  - Association between a casein kinase 1 epsilon gene polymorphism and schizophrenia
      in a Chinese Han population.
AB  - The casein kinase 1 (Csnk1) family of serine/threonine kinases regulates dopamine
      receptor (DR) signaling by phosphorylating the 32-kDa dopamine- and cAMP
      regulated phosphoprotein DARPP-32, leading to inhibition of protein phosphatase 1
      and a shift in the phosphorylation state of many downstream proteins. By
      modulating DR-activated phosphorylation cascades, Csnk1 plays a central role in
      neuropsychiatric disorders and modulates the stimulant response to amphetamine.
      No published study, however, has established a correlation between Csnk1 gene
      polymorphisms and schizophrenia. We genotyped the rs135745C/G polymorphism of the
      Csnk1epsilon gene in 384 schizophrenic patients and 502 healthy controls drawn
      from the Chinese Han population. There were significantly higher CG and CC
      genotype frequencies in schizophrenic patients compared to control subjects (CG,
      p = 0.0086, odds ratio (OR) = 1.477, 95% confidence interval (CI), 1.103-1.978;
      CC, p = 0.0431, OR = 2.571; 95% CI, 0.998-6.624). The C allele frequency was also
      higher in the schizophrenics (p = 0.0022; OR = 1.474; 95% CI, 1.149-1.891). In
      the dominant model, subjects with genotypes CC or CG were at greater risk for
      schizophrenia (p = 0.0032; OR = 1.532; 95% CI, 1.153-2.037), suggesting that a
      genetic variant in the Csnk1epsilon gene significantly enhances the probability
      of schizophrenia in the Chinese Han population.

PMID- 22367617
TI  - Is there an endothelial cell toxicity of light-adjustable lens UVA irradiation on
      the human corneal endothelium?
AB  - PURPOSE: In cataract and refractive surgery, implantation of a light-adjustable
      lens (LAL) represents a promising method to noninvasively correct deviation from
      target refraction. In this method, UVA irradiation is used to induce controlled
      changes in the form and refraction of the lens. UVA irradiation is known to have
      a damaging effect on corneal tissue. So far, no studies about the toxicity of LAL
      treatment on the human corneal endothelium exist. We tested the effect of LAL
      treatment on human donor endothelium under organ culture conditions. METHODS: Two
      pairs of human donor corneas not suitable for transplantation but with good
      endothelial quality were exposed either to LAL treatment with a target refraction
      of the maximum adjustable profile for hyperopia with astigmatism (right corneas)
      or to the white light of the same slit lamp for identical time frames (left
      corneas). Development of endothelial cell number, morphology and percentage of
      necrosis was observed. After 6 weeks, histologic analysis was performed. RESULTS:
      Comparing morphology, cell count, percentage of necrosis, and histologic
      examination in vitro, no significant differences between right and left corneas
      could be detected. CONCLUSIONS: The maximum dose of UVA irradiation used in LAL
      treatment was not detrimental for human corneal endothelium in vitro. Further in
      vivo studies and longer observation periods should be performed for ensuring the
      safety of LAL treatment as a routine procedure.

PMID- 22367618
TI  - Multiple retinal arterial macroaneurysms associated with submacular hemorrhage.
AB  - PURPOSE: To present the unusual case of multiple retinal arterial macroaneurysms
      (RAMs) associated with an extensive submacular hemorrhage. METHODS: A 64-year-old
      hypertensive woman is presented including the clinical findings, fluorescein
      angiography, and optical coherence tomography. RESULTS: The patient presented
      with 20/200 vision due to a dense submacular hemorrhage in the right eye.
      Fluorescein angiography revealed 4 hyperfluorescent lesions along the
      inferotemporal arteriole corresponding to RAMs. Optical coherence tomography
      confirmed RAM rupture with no choroidal abnormality. The patient refused surgical
      intervention. At 3-month follow-up, vision had improved to 20/70 with partial
      resolution of the hemorrhage. However, vitreoretinal traction with neurosensory
      retinal detachment involving the macula had developed. CONCLUSIONS: Acquired RAMs
      are typically found as unilateral solitary lesions in older hypertensive women.
      The presence of 4 RAMs along the same arteriole has not been reported previously.
      Hypertensive patients should be examined regularly in order to detect potential
      RAMs early enough to permit treatment and prevent vision loss.

PMID- 22367621
TI  - Which prediction models best identify additional axillary disease after a
      positive sentinel node biopsy for breast cancer?
AB  - To determine which web-based model best identifies women at low risk of further
      axillary disease after a positive sentinel lymph node (SLN+) biopsy. 673 women
      with T1-2cN0M0 SNB+ breast cancer who underwent completion axillary dissection
      (AxD) were identified. A subgroup not eligible to avoid AxD as part of the Z0011
      study was defined (Z0011 exclusion group). Predicted risk of further axillary
      disease was generated using seven web-based models. "Low risk" was defined as a
      <=10% risk of further axillary disease. False negative ("low risk" prediction but
      AxD+) rates (FNRs), area under the receiver operating characteristic curve (AUC),
      and Brier score were determined for each model. 6 of 7 models identified "low
      risk" patients but FNRs ranged from 14 to 30%. The Stanford and Memorial Sloan
      Kettering (MSKCC) models had the best FNRs. FNRs were lower with SLN
      micrometastasis (7-15%) and higher in the Z0011 exclusion group (21-41%). All
      models under-predicted further nodal disease in low risk patients and over
      predicted in higher-risk patients. The Stanford and MSKCC models were able to
      identify women with SLN micrometastasis with a <=10% FNR. Models were not able to
      accurately identify low risk women from a cohort that would have been excluded
      from Z0011.

PMID- 22367622
TI  - Epigallocatechin-3-gallate prevents TNF-alpha-induced NF-kappaB activation
      thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells.
AB  - The ATP-binding membrane cassette transporter A1 (ABCA1) plays a protective role
      in the development of atherosclerosis for the reverse cholesterol transport
      process. Epigallocatechin-3-gallate (EGCG), which exists abundantly in green tea,
      exerts an anti-atherosclerotic effect via anti-inflammatory and metabolic
      regulation activities. Many genes and proteins related to lipid metabolism are
      involved in the lowering cholesterol effects of EGCG. However, effects of EGCG on
      ABCA1 have rarely been described. In the study presented here, we found that
      exposure of macrophage foam cells to TNF-alpha results in a downregulation of
      ABCA1 and a decrease in cholesterol efflux to apoA1, which is attenuated by
      pretreatment with EGCG. Moreover, rather than activating the Liver X receptor
      (LXR) pathway, inhibition of the TNF-alpha-induced nuclear factor-kappaB (NF
      kappaB) activity is detected with EGCG treatment in cells. In order to inhibit
      the NF-kappaB activity, EGCG can promote the dissociation of the nuclear factor
      E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) complex;
      when the released Nrf2 translocates to the nucleus and activates the
      transcription of genes containing an ARE element inhibition of NF-kappaB occurs
      and Keap1 is separated from the complex to directly interact with IKKbeta and
      thus represses NF-kappaB function. These results provide novel insight into the
      anti-inflammatory effects of EGCG, as well as the identification of a novel
      potential therapeutic role for the prevention of atherosclerosis.

PMID- 22367623
TI  - French validation of the compulsive internet use scale (CIUS).
AB  - The popularity of using the Internet and related applications has grown in
      European countries in the last two decades. Despite numerous advantages in terms
      of optimizing communications among individuals and social systems, the use of the
      Internet may be associated with excessive use and possible Internet addiction.
      The goals of the current study were to validate a French version of the
      compulsive Internet use scale (CIUS) and to assess its links with common
      psychiatric symptoms such as depression (assessed with the Beck depression
      inventory: BDI), anxiety (assessed with the trait anxiety inventory: STAI) and
      alcohol misuse (assessed with the alcohol use disorder identification test:
      AUDIT). The French versions of the CIUS, BDI, STAI and AUDIT were administered to
      a sample of Internet users. Exploratory and confirmatory analyses, correlation
      analysis and logistic regression were performed. As previously found with the
      original version, a one-factor model of the CIUS had good psychometric properties
      and fit the data well. Excessive use of the Internet was associated with
      depressive symptoms.

PMID- 22367624
TI  - Do poor people sue doctors more frequently? Confronting unconscious bias and the
      role of cultural competency.
AB  - BACKGROUND: There is a perception that socioeconomically disadvantaged patients
      tend to sue their doctors more frequently. As a result, some physicians may be
      reluctant to treat poor patients or treat such patients differently from other
      patient groups in terms of medical care provided. QUESTIONS/PURPOSES: We (1)
      examined existing literature to refute the notion that poor patients are inclined
      to sue doctors more than other patients, (2) explored unconscious bias as an
      explanation as to why the perception of the poor being more litigious may exist
      despite evidence to the contrary, and (3) assessed the role of culturally
      competent awareness and knowledge in confronting physician bias. METHODS: We
      reviewed medical and social literature to identify studies that have examined
      differences in litigation rates and related medical malpractice claims among
      socioeconomically disadvantaged patients versus other groups of patients.
      RESULTS: Contrary to popular perception, existing studies show poor patients, in
      fact, tend to sue physicians less often. This may be related to a relative lack
      of access to legal resources and the nature of the contingency fee system in
      medical malpractice claims. CONCLUSIONS: Misperceptions such as the one examined
      in this article that assume a relationship between patient poverty and medical
      malpractice litigation may arise from unconscious physician bias and other social
      variables. Cultural competency can be helpful in mitigating such bias, improving
      medical care, and addressing the risk of medical malpractice claims.

PMID- 22367625
TI  - Does employment-based private health insurance increase the use of covered health
      care services? A matching estimator approach.
AB  - This study estimates the effect of employment-based private health insurance
      (EPHI) on the use of covered health care services based on Danish survey data
      collected in 2009. The paper provides some of the first estimates of how EPHI
      affects the use of health care services in a Scandinavian context. The effect of
      EPHI is estimated using propensity score matching. This method is shown to
      provide plausible estimates given the institutional setting of EPHI in Denmark
      and a wide set of relevant covariates. Considering the full sample of
      occupationally active, it is found that EPHI does not significantly affect the
      probability of having had any hospitalisations, physiotherapist, chiropractor,
      psychologist, specialist, or ambulatory contacts within a 12 month period.
      Restricting the analysis to the subsample of privately employed, the estimated
      effects for ambulatory contacts and hospitalisation are somewhat higher and
      statistically significant. More precisely, it is found that EPHI increases the
      probability of hospitalisation from 5.1 to 8.5% and the probability of having had
      any ambulatory contacts from 17.9 to 23.3% among the privately employed.

PMID- 22367626
TI  - Refractory chronic migraine: long-term follow-up using a refractory rating scale.
AB  - Refractory chronic migraine (RCM) is often associated with disability and a low
      quality of life (QOL). RCM ranges in severity from mild to severe. There would be
      a benefit both clinically and in research use in categorizing RCM patients
      according to severity. This study utilized a unique RCM severity rating scale,
      tracking the clinical course over 10 years. A total of 129 patients, ages 19-72,
      were assigned a severity rating of 2-10 (10 = worst). Pain level and QOL were
      assessed. Over the 10 years, 73% of all pts. had a 30% or more decline in pain.
      Pain levels improved 45% in mild pts., 42% in mod. pts., and 36% in severe pts.
      Pain was the same, or worse, in 4% of mild, 15% of mod., and 18% of severe pts.
      QOL in the mild group improved 35% over 10 years. In moderate pts., QOL improved
      32%, while for the severe group QOL improved 33%. While pain and QOL improved
      across all three groups at the end of 10 years, the severe group remained with
      significantly more pain and decreased QOL than in the milder groups. The
      medications that helped significantly included: opioids (63% of pts. utilized
      opioids), frequent triptans (31%), butalbital (17%), onabotulinumtoxinA (16%),
      stimulants (12%), and other "various preventives" (9%). RCM pts. were rated using
      a refractory rating scale with the clinical course assessed over 10 years. Pain
      and QOL improved in all groups. In the severe group, pain and QOL improved, but
      still lagged behind the mild and moderate groups. Opioids and (frequent) triptans
      were the most commonly utilized meds.

PMID- 22367627
TI  - Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary
      experience.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by NOTCH3
      mutations. It is characterized by migraine, with or without aura, ischemic
      events, psychiatric and cognitive disturbances. There is no approved treatment
      for migraine prophylaxis in CADASIL, but acetazolamide has been anecdotally
      reported to be effective. We retrospectively reviewed our database of patients
      with a genetic diagnosis of CADASIL to identify how many of them were treated
      with acetazolamide for the prophylaxis of migraine. The efficacy and the
      tolerability of this treatment were checked looking at the clinic reports.
      Acetazolamide was prescribed in seven patients; the mean duration of treatment
      was 6 months, and the daily dose ranged from 125 to 500 mg. Three patients had a
      total and sustained remission, while in two patients a reduction in attacks and
      an improvement of the headache intensity were recorded. In one of these,
      acetazolamide was deliberately taken only during the migraine attack and the
      beneficial effect started 1 h after administration. In two patients, the drug did
      not produce any beneficial effect. Mild side effects were recorded in two
      patients. Our preliminary experience expands previous reports and confirms the
      possible efficacy of acetazolamide in CADASIL migraine. Based on these data, a
      randomized controlled trial seems worthy to be carried out to test the efficacy
      and safety of this drug.

PMID- 22367628
TI  - Assessment of pain and analgesic use in African American cancer patients: factors
      related to adherence to analgesics.
AB  - This study describes pain experience, analgesic use and barriers to pain control
      in African American cancer patients (N = 116). The overall adherence rate of
      analgesics was 46%. Constipation and nausea were the most commonly cited side
      effects of analgesics. Eighty-seven percent of patients reported concern about
      addiction to analgesics. Patients who believed their doctor needed to focus on
      curing illness rather than on controlling pain tended to comply with analgesic
      prescriptions (r = 0.20, p < 0.05). Patients with concerns that analgesics may
      cause confusion were less likely to take any type of analgesics (r = -0.16, p <
      0.05). The study confirms that a patient's perceived barriers influence their
      decision to take analgesics, and also suggests that African American cancer
      patients may benefit from education that prevents misconceptions about analgesic
      use.

PMID- 22367629
TI  - A small molecule modulator of prion protein increases human mesenchymal stem cell
      lifespan, ex vivo expansion, and engraftment to bone marrow in NOD/SCID mice.
AB  - Human mesenchymal stem cells (hMSCs) have been shown to have potential in
      regenerative approaches in bone and blood. Most protocols rely on their in vitro
      expansion prior to clinical use. However, several groups including our own have
      shown that hMSCs lose proliferation and differentiation ability with serial
      passage in culture, limiting their clinical applications. Cellular prion protein
      (PrP) has been shown to enhance proliferation and promote self-renewal of
      hematopoietic, mammary gland, and neural stem cells. Here we show, for the first
      time, that expression of PrP decreased in hMSC following ex vivo expansion. When
      PrP expression was knocked down, hMSC showed significant reduction in
      proliferation and differentiation. In contrast, hMSC expanded in the presence of
      small molecule 3/689, a modulator of PrP expression, showed retention of PrP
      expression with ex vivo expansion and extended lifespan up to 10 population
      doublings. Moreover, cultures produced a 300-fold increase in the number of cells
      generated. These cells showed a 10-fold increase in engraftment levels in bone
      marrow 5 weeks post-transplant. hMSC treated with 3/689 showed enhanced
      protection from DNA damage and enhanced cell cycle progression, in line with data
      obtained by gene expression profiling. Moreover, upregulation of superoxide
      dismutase-2 (SOD2) was also observed in hMSC expanded in the presence of 3/689.
      The increase in SOD2 was dependent on PrP expression and suggests increased
      scavenging of reactive oxygen species as mechanism of action. These data point to
      PrP as a good target for chemical intervention in stem cell regenerative
      medicine.

PMID- 22367630
TI  - Placebo and other psychological interactions in headache treatment.
AB  - We present a theory according which a headache treatment acts through a specific
      biological effect (when it exists), a placebo effect linked to both expectancy
      and repetition of its administration (conditioning), and a non-specific
      psychological effect. The respective part of these components varies with the
      treatments and the clinical situations. During antiquity, suggestions and beliefs
      were the mainstays of headache treatment. The word placebo appeared at the
      beginning of the eighteenth century. Controversies about its effect came from an
      excessive interpretation due to methodological bias, inadequate consideration of
      the variation of the measure (regression to the mean) and of the natural course
      of the disease. Several powerful studies on placebo effect showed that the nature
      of the treatment, the associated announce, the patients' expectancy, and the
      repetition of the procedures are of paramount importance. The placebo expectancy
      is associated with an activation of pre-frontal, anterior cingular, accumbens,
      and periacqueducal grey opioidergic neurons possibly triggered by the
      dopaminergic meso-limbic system. In randomized control trials, several arms
      design could theoretically give information concerning the respective part of the
      different component of the outcome and control the natural course of the disease.
      However, for migraine and tension type headache attacks treatment, no three arm
      (verum, placebo, and natural course) trial is available in the literature.
      Indirect evidence of a placebo effect in migraine attack treatment, comes from
      the high amplitude of the improvement observed in the placebo arms (28% of the
      patients). This figure is lower (6%) when using the harder criterium of pain free
      at 2 h. But these data disregard the effect of the natural course. For
      prophylactic treatment with oral medication, the trials performed in the last
      decades report an improvement in 21% of the patients in the placebo arms.
      However, in these studies the duration of administration was limited, the control
      of attacks uncertain as well as the evolution of the co-morbid psycho-pathology.
      Considering the reviews and meta-analysis of complex prophylactic procedures, it
      must be concluded that their effect is mostly linked to a placebo and non
      specific psychological effects. Acupuncture may have a slight specific effect on
      tension type headache, but not on migraine. Manual therapy studies do not exhibit
      difference between manipulation, mobilization, and controls; touch has no proven
      specific effect. A comprehensive efficacy review of biofeedback studies concludes
      to a small specific effect on tension type headache but not on migraine. A review
      of behavioral treatment conclude to an interesting mean improvement but did not
      demonstrated a specific effect with the exception of a four arm study including a
      pseudo meditation control group. Expectation-linked placebo, conditioning, and
      non-specific psychological effects vary according clinical situations and
      psychological context; likely low in RCT, high after anempathic medical contact,
      and at its maximum with a desired charismatic healer. The announcements of
      doctors strongly influence the beliefs of patients, and in consequence their pain
      and anxiety sensibilities; this modulates the amplitude of the placebo and the
      non-specific psychological effects and is therefore a major determinant of the
      therapeutic success. Furthermore, any repetitive contact, even through a placebo,
      may interfere positively with the psychopathological co-morbidity. One has to
      keep in mind that the non-specific psychological interactions play a major role
      in the improvement of the majority of the headache sufferers.

PMID- 22367632
TI  - Three new aliphatic glycosides from the leaves of Antidesma japonicum Sieb. et
      Zucc.
AB  - From the 1-BuOH-soluble fraction of an MeOH extract of leaves of Antidesma
      japonicum, three new aliphatic glycosides, alpha-L-arabinofuranosyl-(1 -> 6)-beta
      D-glucopyranosides of (6R,9R)-megastigma-4,7-dien-9-ol-3-one, (Z)-hex-3-en-1-ol,
      and methyl 2-hydroxy-2-(1'-hydroxyethyl)pentanoate 1'-O-beta-D-glucopyranoside,
      were isolated, along with seven known compounds.

PMID- 22367631
TI  - Migraine in women: the role of hormones and their impact on vascular diseases.
AB  - Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy,
      and menopause, and also the use of hormonal contraceptives and hormone
      replacement treatment may influence migraine occurrence. Migraine usually starts
      after menarche, occurs more frequently in the days just before or during
      menstruation, and ameliorates during pregnancy and menopause. Those variations
      are mediated by fluctuation of estrogen levels through their influence on
      cellular excitability or cerebral vasculature. Moreover, administration of
      exogenous hormones may cause worsening of migraine as may expose migrainous women
      to an increased risk of vascular disease. In fact, migraine with aura represents
      a risk factor for stroke, cardiac disease, and vascular mortality. Studies have
      shown that administration of combined oral contraceptives to migraineurs may
      further increase the risk for ischemic stroke. Consequently, in women suffering
      from migraine with aura caution should be deserved when prescribing combined oral
      contraceptives.

PMID- 22367633
TI  - Pharmacokinetics of the main compounds absorbed into blood after oral
      administration of Liu Wei Di Huang Wan, a typical combinatorial intervention of
      Chinese medical formula.
AB  - Liu Wei Di Huang Wan (LW) has been used as an active Chinese patent formula for
      "Five Late Syndrome" of Children for thousands of years. Due to the complexity in
      its chemical constituents, the pharmacokinetics of this formula have not been
      elucidated clearly, and the understanding of its pharmacological properties has
      been delayed. Previous studies have identified the constituents absorbed into
      blood after the oral administration of LW; moreover, 5-hydroxymethyl-2-furoic
      acid (HMFA), loganin and paeonol have been proved as surrogate markers. In this
      study, a rapid validated high-performance liquid chromatography method was
      developed for determining three marker compounds in plasma. The analysis was
      performed on a Waters Symmetry ShieldTM RP(18) column with acetonitrile and 0.15%
      phosphoric acid as the mobile phase, which showed acceptable linearity, intra-
      and inter-day precision, and accuracy. By using the established method, the
      pharmacokinetic analysis of LW was carried out. The t (1/2)alpha and t (1/2)beta
      were 2.62/32.66, 0.46/4.71 and 1.30/23.51 h and the climax times and
      concentrations were 0.56/683.75, 0.70/2826.11 and 0.62 h/4030.48 ng ml(-1) for
      HMFA, loganin and paeonol, respectively. Especially, both the absorption and
      disposition of HMFA were swift (t (1/2) kalpha 0.1 h, t (1/2)alpha 2.62 h), but
      the elimination was quite slow (t (1/2)beta 32.66 h); this phenomenon reflected
      the synergetic effect of LW combinatorial intervention and the value of
      compatibility can be more clearly understood. The pharmacokinetic characters of
      HMFA, loganin and paeonol not only elucidated the steady and long-lasting
      pharmacological properties, but they also revealed the practical value of the
      compatibility of Chinese medical formula.

PMID- 22367634
TI  - 3D-QSAR study of Chk1 kinase inhibitors based on docking.
AB  - Checkpoint kinase 1 (Chk1), a kind of a serine/threonine protein kinase, plays a
      significant role in DNA damage-induced checkpoints. Chk1 inhibitors have been
      demonstrated to abrogate the S and G2 checkpoints and disrupt the DNA repair
      process, which results in immature mitotic progression, mitotic catastrophe, and
      cell death. Normal cells remain at the G1 phase via p53 to repair their DNA
      damages, and are less influenced by the abrogation of S and G2 checkpoint.
      Therefore, selective inhibitors of Chk1 may be of great therapeutic value in
      cancer treatment. In this paper, in order to understand the structure-activity
      relationship of macro-cyclic urea Chk1 inhibitors, a study combined molecular
      docking and 3D-QSAR modeling was carried out, which resulted in two substructure
      based 3D-QSAR models, including the CoMFA model (r(2), 0.873; q(2), 0.572) and
      CoMSIA model (r(2), 0.897; q(2), 0.599). The detailed microscopic structures of
      Chk1 binding with inhibitors were performed by molecular docking. Two docking
      based 3D-QSAR models were developed (CoMFA with r(2), 0.887; q(2), 0.501; CoMSIA
      with r(2), 0.872; q(2), 0.520). The contour maps obtained from the 3D-QSAR models
      in combination with the docked binding structures would be helpful to better
      understand the structure-activity relationship. All the conclusions drawn from
      both the 3D-QSAR contour maps and molecular docking were in accordance with the
      experimental activity dates. The results suggested that the developed models and
      the obtained CHk1 inhibitor binding structures might be reliable to predict the
      activity of new inhibitors and reasonable for the future drug design.

PMID- 22367635
TI  - Conceptual equivalence of WHOQOL-HIV among people living with HIV in Ethiopia.
AB  - PURPOSE: The WHOQOL instruments are intended for cross-cultural studies of
      quality of life (QoL) but African countries have been poorly represented in its
      development. This study aimed to explore the conceptual equivalence of WHOQOL-HIV
      in Ethiopia. METHODS: The fieldwork included home visits, interviews, and focus
      group discussions with HIV patients and caregivers. RESULTS: We found that
      although WHOQOL-HIV includes many relevant facets, its applicability has several
      limitations in the Ethiopian setting. The most salient shortcomings of the
      instrument relate to the Social, Environmental and Religion/Spirituality/Personal
      Beliefs domains of the instrument. Themes not captured by the instrument include
      family responsibilities, disease disclosure, exclusion from common resources,
      basic needs, adequate food, and job opportunities. In addition, several of the
      tool's facets such as dependence on medicine seem less relevant. Also, the role
      of religion is more complex than captured in WHOQOL-HIV. We found that the tool
      is based on an individualist focus, which tends to overlook the social context of
      the patient. CONCLUSION: We conclude that the conceptual equivalence of WHOQOL
      HIV is only partially attained for use in Ethiopia. The findings from this
      qualitative study are used in the further process of developing and validating a
      QoL instrument for use in Ethiopia.

PMID- 22367636
TI  - Influence of exogenous CO2 on biomass and lipid accumulation of microalgae
      Auxenochlorella protothecoides cultivated in concentrated municipal wastewater.
AB  - The effects of exogenous CO2 on the growth and lipid accumulation of a local
      screened facultative heterotrophic microalgae strain Auxenochlorella
      protothecoides (UMN280) as well as nutrient removal from concentrated municipal
      wastewater stream (centrate) were examined in this study. A 12-day batch
      experiment was conducted with CO2 aeration at three levels, namely, 0%, 1%, and
      5% (v/v) CO2 mixed with air, under light intensity of 60 MUmol/(m2 @@s). A two
      stage growth pattern was observed. The first stage (first-fifth day) was
      dominated by heterotrophic growth in which organic carbon was the main carbon
      source. The second stage (6th-12th day) was dominated by autotrophic growth in
      which exogenous CO2 had a positive effect on algal biomass accumulation. The
      addition of 5% CO2 was better than that of 1% CO2 on the biomass and lipid
      production. The uptakes of nutrients were similar between injection and no
      injection of CO2, except on phosphorus removal which was affected by the
      acidification of CO2.

PMID- 22367637
TI  - Degradation of polyurethane by Aspergillus flavus (ITCC 6051) isolated from soil.
AB  - The present study deals with the isolation of fungi from soil with the ability to
      degrade polyurethane (PU). A pure fungal isolate was analyzed for its ability to
      utilize PU as a sole carbon source in shaking culture for 30 days. Incubation of
      PU with Aspergillus flavus resulted in 60.6% reduction in weight of PU. The
      scanning electron microscopy and Fourier transform infrared spectroscopy (FTIR)
      results showed certain changes on the surface of PU film and formation of some
      new intermediate products after polymer breakdown. Thermogravimetric curves
      showed changes between the thermal behavior of the samples that were inoculated
      with A. flavus and control. FTIR spectra showed detectable changes in control and
      incubated samples, suggesting that degradation occurs, with the decreased
      intensity of band at 1,715 cm(-1), corresponding to ester linkages. We have
      identified an extracellular esterase activity which might be responsible for the
      polyurethanolytic activity.

PMID- 22367638
TI  - A temperature and salt-tolerant L-glutaminase from gangotri region of uttarakhand
      himalaya: enzyme purification and characterization.
AB  - Purification and characterization of halotolerant, thermostable alkaline L
      glutaminase from a Bacillus sp. LKG-01 (MTCC 10401), isolated from Gangotri
      region of Uttarakhand Himalaya, is being reported in this paper. Enzyme has been
      purified 49-fold from cell-free extract with 25% recovery (specific activity
      584.2 U/mg protein) by (NH4)2SO4 precipitation followed by anion exchange
      chromatography and gel filtration. Enzyme has a molecular weight of 66 kDa. L
      Glutaminase is most active at pH 11.0 and stable in the pH range 8.0-11.0.
      Temperature optimum is 70  degrees C and is completely stable after 3 h pre
      incubation at 50  degrees C. Enzyme reflects more enhanced activity with 1-20%
      (w/v) NaCl, which is further reduced to 80% when NaCl concentration was increased
      up to 25%. L-Glutaminase is almost active with K+, Zn2+, and Ni2+ ions and K(m)
      and V(max) values of 240 MUM and 277.77 +/- 1.1 U/mg proteins, respectively.
      Higher specific activity, purification fold, better halo-tolerance, and
      thermostability would make this enzyme more attractive for food fermentation with
      respect to other soil microbe derived L-glutaminase reported so far.

PMID- 22367639
TI  - Multiplexed detection of waterborne pathogens in circular microfluidics.
AB  - Microfluidic lab-on-a-chip presents an ideal solution for bacterial sensing and
      identification due to its advantages like large surface-to-volume ratio,
      requirement of low sample volume and multiplexing possibility. The present work
      deals with the development of an immunosensor chip using circular microchannels
      fabricated directly with microdimensional copper wire and permanent magnet for
      capture of Fe(3)O(4) magnetic nanoparticle (MNP) conjugate. The MNP facilitate
      capture of the antigen in a confined space and hence, enhanced fluorescence
      signal for detection. The multiplexed microfluidic chip permits visual detection
      and quantification of waterborne pathogens viz. Escherichia coli and Salmonella
      typhimurium simultaneously. CdTe quantum dots (QDs) with different emission
      wavelengths were conjugated with anti-E. coli and anti-S. typhimurium antibodies
      for concurrent fluorescence detection. The present technique provides an
      inexpensive yet powerful tool to image and quantify pathogens at low numbers with
      passage of large sample volumes.

PMID- 22367640
TI  - Rheological behavior and non-enzymatic degradation of a sulfated galactan from
      Halymenia durvillei (Halymeniales, Rhodophyta).
AB  - The rheological behavior of a sulfated galactan extracted from Halymenia
      durvillei, a red seaweed collected in the coastal waters of a small island of
      Madagascar (Nosy-be in Indian Ocean), was investigated in dilute and semi-dilute
      solutions. In dilute solution with NaCl at 0.3 M, the polysaccharide adopted a
      coil conformation whereas, at higher concentrations, the polymer had the behavior
      of shear-thinning fluid, typical of polymer with high molar mass or semi-rigid
      conformation. Degradations of this lambda carrageenan-like, using radical
      depolymerization, and high-pressure homogenization led to several samples of
      various and controlled molar masses. The measure of their intrinsic viscosities
      permitted the determination of the relationship of Mark-Houwink-Sakurada.

PMID- 22367641
TI  - Characterization of simultaneous heat and mass transfer phenomena for water
      vapour condensation on a solid surface in an abiotic environment--application to
      bioprocesses.
AB  - The phenomenon of heat and mass transfer by condensation of water vapour from
      humid air involves several key concepts in aerobic bioreactors. The high
      performance of bioreactors results from optimised interactions between biological
      processes and multiphase heat and mass transfer. Indeed in various processes such
      as submerged fermenters and solid-state fermenters, gas/liquid transfer need to
      be well controlled, as it is involved at the microorganism interface and for the
      control of the global process. For the theoretical prediction of such phenomena,
      mathematical models require heat and mass transfer coefficients. To date, very
      few data have been validated concerning mass transfer coefficients from humid air
      inflows relevant to those bioprocesses. Our study focussed on the condensation
      process of water vapour and developed an experimental set-up and protocol to
      study the velocity profiles and the mass flux on a small size horizontal flat
      plate in controlled environmental conditions. A closed circuit wind tunnel
      facility was used to control the temperature, hygrometry and hydrodynamics of the
      flow. The temperature of the active surface was controlled and kept isothermal
      below the dew point to induce condensation, by the use of thermoelectricity. The
      experiments were performed at ambient temperature for a relative humidity between
      35-65% and for a velocity of 1.0 ms-1. The obtained data are analysed and
      compared to available theoretical calculations on condensation mass flux.

PMID- 22367642
TI  - Advances in non-snake venom L-amino acid oxidase.
AB  - L-amino acid oxidase is widely found in diverse organisms and has different
      properties. It is thought to contribute to antimicrobial activity, amino acid
      catabolism, and so forth. The purpose of this communication is to summarize the
      advances in non-snake venom L-amino acid oxidase, including its enzymatic and
      structural properties, gene cloning and expression, and biological function. In
      addition, the mechanism of its biological function as well as its application is
      also discussed.

PMID- 22367643
TI  - Intraspecific differentiation of Colletotrichum gloeosporioides sensu lato based
      on in silico multilocus PCR-RFLP fingerprinting.
AB  - Colletotrichum gloeosporioides sensu lato is one of the most common and widely
      distributed plant pathogens in the world. Understanding fungal biodiversity is
      hinged on accurate identification and delimitation at the inter- and
      intraspecific levels. Sequences of the ITS1-5.8S-ITS2 region (ITS), beta-tubulin
      (TUB), actin (ACT), and glyceraldehyde-3-phosphate dehydrogenase (GPDH) genes of
      30 C. gloeosporioides sensu lato isolates, collected from anthracnose infected
      papaya fruits grown in the main production areas in Trinidad, were analyzed by in
      silico PCR-RFLP analysis with the aim of identifying which gene region(s) had the
      highest level of intraspecific polymorphism. Restriction site polymorphisms
      generated from 13 restriction enzymes enabled the identification of specific
      enzymes that were successful at intraspecific discrimination of the C.
      gloeosporioides isolates. Genetic distance values were reflective of the level of
      polymorphisms obtained for the four different gene regions. In both cases
      (calculated genetic distance and percentage of polymorphic loci from RFLP
      profiles), ACT and ITS gene regions had the highest level of restriction site
      polymorphisms and genetic diversity, GPDH and TUB had the lowest. Cluster
      analysis based on PCR-RFLP genetic distance data revealed sub-specific placement
      of the isolates which appeared to be gene-dependent. The implications of these
      findings are discussed relative to biodiversity monitoring and the need for
      multilocus, polyphasic investigations which must take into account the
      possibility of exaggerated estimates of genetic diversity.

PMID- 22367644
TI  - Quantitative expression analysis of TaSOS1 and TaSOS4 genes in cultivated and
      wild wheat plants under salt stress.
AB  - Salt stress is a mixture of ionic, osmotic, and oxidative stresses. The
      expression of TaSOS1 (a transmembrane Na(+)/H(+) antiporter) and TaSOS4 [a
      cytoplasmic pyridoxal (PL) kinase] genes were measured in four different salinity
      levels and different time courses of salinity exposure using qRT-PCR technique.
      Mahuti (salt tolerant) and Alamut (salt sensitive) cultivars were used as
      cultivated wheat, and T. boeticum and Aegilops crassa as wild wheat plants. Salt
      induced expression of TaSOS1 in these wild wheat plants indicates the presence of
      active TaSOS1 gene on the genomes A and D. The TaSOS1 and TaSOS4 transcript
      levels were found to be downregulated after salt treatment in all cultivars
      except in A. crassa, which was in contrast with its expression pattern in roots
      that was being upregulated from a very low-basal expression, after salt
      treatments. Duncan's Multiple Range Test showed a significant difference between
      expression in the 200-mM NaCl concentration with the 50 and 100 mM for the TaSOS1
      gene, and no significant difference for TaSOS4. Lack of significant correlation
      between the TaSOS1 and TaSOS4 gene expressions confirms the theory that PLP has
      no significant effect on the expression of the TaSOS1 gene in wheat leaves.

PMID- 22367645
TI  - Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled
      in the HERA trial (BIG 01-01).
AB  - Only few case reports describe the pregnancy course and outcome of breast cancer
      patients, who were under treatment with trastuzumab at the time of conception or
      who have completed trastuzumab therapy before becoming pregnant. The HERA trial
      is a large phase III randomized clinical trial in which patients with early HER2
      positive breast cancer were randomized to receive 1 or 2 years of trastuzumab or
      observation following completion of primary chemotherapy. To examine the effect
      of trastuzumab on pregnancy outcome, we report all pregnancy events that occurred
      until March 2010 in patients enrolled in the study. For the sake of this
      analysis, patients were assigned to three groups: (1) pregnancy occurring during
      and up to 3 months after trastuzumab exposure (group 1); (2) pregnancy occurring
      >3 months of last trastuzumab dose (group 2); and (3) pregnancy occurring in
      patients without prior exposure to trastuzumab (group 3). Sixteen, 45 and 9
      pregnancies took place in groups 1, 2, and 3, respectively. 25 and 16% of
      patients in groups 1 and 2 experienced spontaneous abortion, the former being
      higher than figures reported in the general population. However, short-term fetal
      outcome appeared normal across the three groups. Only 2 congenital anomalies were
      reported, one in group 2 and one in group 3. No congenital anomalies were
      reported in those exposed to trastuzumab in utero. This is the first report from
      a large randomized trial assessing the effect of trastuzumab on pregnancy course
      and outcome. Based on our results, trastuzumab does not appear to affect fetal
      outcome in patients who manage to complete their pregnancy. We are currently
      initiating a collaboration to collect similar data from the other large adjuvant
      trastuzumab trials to confirm these findings.

PMID- 22367646
TI  - Allogenous vein graft as vascular access for hemodialysis--lost battle?
AB  - PURPOSE: The purpose of this paper is to assess a long-term outcome of allogenous
      vein grafts (ALVG) as vascular access for hemodialysis. MATERIALS AND METHODS:
      For nearly eight years (between 9/2002 and 9/2011) a total of 78 patients with
      112 ALVGs were involved in the study. The register included 46 women and 32 men,
      mean age 66.1 +/- 11.2 years; range 20-88 years. The patient database was
      retrospectively reviewed and statistical processing was performed. RESULTS:
      Almost all ALVGs were treated by PTA or surgically, very often repeatedly. The
      number of radiologic interventions was 316, the number of surgical procedures 31.
      Mean follow-up time was 795 days, range 28-3522 days. Thirty-five patients died
      of unrelated causes, nineteen with functional graft, fourteen patients were lost
      to follow-up. Forty ALVGs failed for various reasons, mostly because of
      occlusion. Only one patient underwent successful renal transplantation, no
      patient converted to peritoneal dialysis. Thirty-seven ALVGs remain correctly
      functioning. Primary patency rates at 6, 12, and 24 months were 81 +/- 5%, 63 +/-
      5%, and 34 +/- 2% respectively. Secondary patency rates at 6, 12, and 24 months
      were 96 +/- 2%, 82 +/- 4%, and 65 +/- 5% respectively. CONCLUSIONS: Allogenous
      vein grafts, in spite of the high number of necessary radiologic and surgical
      interventions and reinterventions, show acceptable clinical usability and
      durability, comparable with other types of prosthetic grafts.

PMID- 22367647
TI  - Dealing with vanishing central veins.

PMID- 22367648
TI  - Percutaneous approach in the maintenance and salvage of dysfunctional autologous
      vascular access for dialysis.
AB  - PURPOSE: Endovascular procedures have been increasingly used for salvage of
      failing vascular access with conflicting results. The aim of this study was to
      assess the mid-term patency and complication rates of angioplasty procedures
      performed in a single center for treatment of stenosis compromising vascular
      accesses. METHODS: A prospective database of vascular accesses performed in 2006
      2010 was investigated. The endovascular approach was applied following a
      standardized protocol by a dedicated team. A total of 531 consecutive procedures
      were reviewed (326 men; mean age 70.94 years). Patency rates were estimated using
      the Kaplan-Meier method. RESULTS: There were 199 procedures for failing access:
      135 were surgical and 64 angioplasties performed for anastomosis (n=27), venous
      (n=45) or arterial (n=7) stenosis. Immediate technical success of endovascular
      procedures was 95.3%(61/64); complication rate was 6.3% (4/64). Primary patency
      rates were 55% at six months, 49% at 12 months, and 21% at 24 months. In the
      concurrent group of 135 open procedures, primary patency rates were 80% at six
      months and 67% at 12 months (P=.002); nevertheless, at 24 months, patency was as
      low as 49%. Cost estimates for angioplasty revealed additional fees ranging from
      411.34 to 446.34 Euro with respect to open surgical procedures. CONCLUSIONS: Most
      dysfunctional vascular accesses can be successfully and safely treated by the
      endovascular route. In spite of poor mid-term durability, the angioplasty balloon
      might be considered as a bridge, effective, and repeatable solution with
      reasonable costs to prolong access survival avoiding additional surgery. The
      failure rate in the mid-term for dysfunctional vascular access may also be high
      after surgical reintervention.

PMID- 22367649
TI  - A proposed management algorithm for fistulae between hemodialysis access circuits
      and adjacent veins.
AB  - PURPOSE: Fistulae between an arteriovenous hemodialysis graft (AVG) or fistula
      (AVF) and an adjacent vein are an unusual complication of hemodialysis access.
      Such fistulae may theoretically cause steal syndrome, extremity edema, or access
      dysfunction. We sought to use our experience and existing literature to develop a
      management algorithm for this access complication. METHODS: Twelve patients with
      AVG/AVF to adjacent vein fistulae found on fistulography were identified using a
      quality assurance database. Indications for fistulography, treatment rendered for
      both the fistulae and access stenosis, and outcome of treatment were determined.
      AVG/AVF to adjacent vein fistulae, when identified and considered to be
      significant, were treated with embolization. RESULTS: Five out of twelve patients
      had successful embolization of their AVG/AVF to adjacent vein fistulae. Reasons
      for treatment included partial thrombosis of the access to the level of the
      fistula (n=1), contribution to bleeding during dialysis (n=1), and concern for
      competing flow causing thrombosis (n=5). No recurrence was identified. Seven
      patients did not undergo embolization either because of failure to recognize the
      fistula (n=3) or determination that treatment was not indicated (n=4). Two
      untreated fistulae were found occluded at follow-up. Additional access treatment
      included angioplasty (n=11), covered stent (n=1), and mechanical thrombectomy
      (n=3). CONCLUSIONS: The significance of AVG/AVF to adjacent vein fistulae remains
      unclear; some resolve spontaneously, possibly related to PTA of outflow stenosis.
      Embolotherapy is an effective treatment for such fistulae when determined to be
      significant.

PMID- 22367650
TI  - US psychiatric residents' treatment of patients with bipolar disorder.
AB  - We aimed to evaluate the practice patterns of US postgraduate year (PGY) levels 3
      and 4 psychiatric residents in the treatment of patients with bipolar disorder
      (BD) types I and II. We also aimed to determine whether confidence in prescribing
      mood stabilizers is associated with residents' practice patterns. The residency
      training directors of 182 Accreditation Council for Graduate Medical Education
      accredited US psychiatric residencies were solicited for study participation via
      e-mail. Their chief residents were asked to forward an online survey Web link to
      all PGY-3 and PGY-4 residents in their program. The survey was a cross-sectional,
      online questionnaire, evaluating residents' treatment choices for their BD
      patients in their psychopharmacology clinics during the last academic year (July
      1, 2009, to May 1, 2010), along with resident confidence level in using mood
      stabilizers. The survey Web link was distributed to 769 residents, and 177
      (23.0%) responded to the survey. The percentage of residents who did not initiate
      treatment in the past year with mood stabilizers was 24.5% for lithium, 26.9% for
      lamotrigine, 36.7% for valproate, and 73.6% for carbamazepine. Confidence in
      initiating treatment with each of the 4 mood stabilizers was significantly
      associated with the number of patients treated with each mood stabilizer in the
      past year. Residents reported having the lowest confidence with carbamazepine
      followed by lamotrigine, lithium, and valproate. Experience prescribing first
      line treatments for BD, such as lithium and valproate, is inadequate for many US
      psychiatric residents. Psychiatry residency directors should ensure that their
      residents have sufficient opportunity to pharmacologically treat BD patients so
      that these young physicians may develop confidence using an array of evidence
      based treatments.

PMID- 22367651
TI  - Sedative load among community-dwelling people aged 75 years or older: association
      with balance and mobility.
AB  - Drugs with sedative properties are frequently used among older people. Sedative
      load is a measure of the cumulative effect of taking multiple drugs with sedative
      properties. The objective of this study was to investigate the association
      between sedative load and balance and mobility. A random sample of 1000 people 75
      years or older was invited to participate. Seven hundred community-dwelling
      participants (mean age, 81.3 years; 69% women) were included in the present
      study. Demographic, diagnostic, and drug use data were elicited during nurse
      interviews in 2004. Balance and mobility were tested by physiotherapists.
      Sedative load was calculated using a previously published model for each
      participant by summing the sedative ratings of primary sedatives (rating 2) and
      drugs with sedation as a prominent adverse effect (rating 1). Analyses of
      covariance and logistic regression analyses were used to assess the association
      between sedative load and balance and mobility. Of the 700 participants, 21% (n =
      147) had a sedative load of 1-2, and 8% (n = 58) had sedative load of 3 or
      greater. After adjusting for covariates, exposure to higher sedative load ranges
      was associated with slower walking speed (P = 0.0003), longer time to perform
      Timed Up and Go test (P = 0.005), and lower scores on Berg Balance Scale (P =
      0.005), but not with self-reported ability to walk 400 m. In conclusion, having a
      higher sedative load was associated with impaired balance and mobility among
      community-dwelling older people. Clinicians should remain cognizant of this
      association and regularly reevaluate drug therapy prescribed to older people.

PMID- 22367652
TI  - Combination of antidepressants in the treatment of major depressive disorder: a
      systematic review and meta-analysis.
AB  - The objective was to perform a systematic review and meta-analysis of studies
      that assessed the effect of the combination of antidepressants from the beginning
      of the treatment of major depressive disorder. Studies were retrieved from PubMed
      (1966 to August 2010), Cochrane Library (August 2010), Embase (1980 to August
      2010), PsycINFO (1980 to August 2010), Lilacs (1982 to August 2010), clinical
      trials registry, thesis database (www.capes.gov.br), and secondary references.
      All randomized controlled trials that compared a combination of antidepressants
      with a single antidepressant from the beginning of the treatment of major
      depressive disorder in adults were included. Data analysis was performed using
      the Review Manager 5.0. Of 3492 studies retrieved, five satisfied the inclusion
      criteria. In one study, only data about dropouts were included. Antidepressant
      combination was shown to be better than a single antidepressant considering
      remission (relative risk [RR], 2.71; 95% confidence interval [CI], 1.69-4.35) and
      response (RR, 1.55; 95% CI, 1.21-1.97). Mirtazapine plus selective serotonin
      reuptake inhibitor (SSRI) was superior to an isolated SSRI for remission (RR,
      1.88; 95% CI, 1.06-3.33). Tricyclic antidepressant plus SSRI was superior to SSRI
      for remission and response (RR, 8.58; 95% CI, 1.70-43.32 and RR, 1.78; 95% CI,
      1.07-2.93, respectively). There was no difference between combined and
      monotherapy groups in dropouts owing to adverse effects. The results suggest that
      antidepressant combination is more efficient than a single antidepressant without
      a significant decrease in tolerability. However, the small number of clinical
      trials and methodological problems precludes definitive conclusions.

PMID- 22367653
TI  - Effects of drug burden index on cognitive function in older men.
AB  - We aimed to assess the relationship between Drug Burden Index (DBI), a risk
      assessment tool that measures anticholinergic and sedative medication exposure
      and cognitive performance, and cognitive impairment in older people. The study
      population consisted of community-dwelling older men, 70 years or older, living
      in Sydney, Australia. The Addenbrooke's Cognitive Examination (ACE) and the Trail
      Making Task (TMT) cognitive tests were performed, and participants were
      categorized as having intact cognition, mild cognitive impairment, or dementia
      using clinical diagnostic criteria. The analyses were restricted to participants
      with English-speaking background (n = 987) and to the subgroup whose cognition
      was intact (n = 887). In the study group, DBI exposure was not associated with
      poorer performance on the ACE (odds ratio [OR], 0.98; 95% confidence interval
      [CI], 0.66-1.47) or the TMT (OR, 0.71; 95% CI, 0.40-1.24) tests, after
      controlling for covariates. Similarly, DBI exposure was not associated with
      cognitive impairment (OR, 1.34; 95% CI, 0.83-2.16). There was no association
      between increasing DBI scores and poorer performance on any of the outcomes. On
      subgroup analysis of cognitively intact subgroup, DBI exposure or increasing DBI
      scores were not associated with poorer performance on the ACE or the TMT tests.
      In this study of community-dwelling older men, DBI was not associated with
      limitations on objective cognitive performance measures or with a clinical
      diagnosis of mild cognitive impairment or dementia.

PMID- 22367654
TI  - A randomized, placebo-controlled study of zonisamide to prevent olanzapine
      associated weight gain.
AB  - Weight gain is commonly observed with olanzapine treatment. Zonisamide is an
      antiepileptic drug associated with weight loss. This study examined the
      effectiveness of zonisamide in preventing weight gain in 42 patients beginning
      olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass
      index of 22 mg/kg or greater and was randomized to taking olanzapine with either
      zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure
      was change in body weight in kilograms from baseline. In the primary analysis
      using longitudinal regression, patients who received zonisamide had a
      significantly slower rate of weight gain and increase in body mass index than
      those who received placebo. The patients treated with zonisamide gained a mean
      (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of
      5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared
      with 7 patients (33%) in the placebo group, gained 7% of body weight or greater
      from baseline (Fisher exact test, P = 0.009). The zonisamide group, however,
      reported significantly more cognitive impairment as an adverse event than the
      placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for
      mitigating weight gain in patients with bipolar disorder or schizophrenia
      initiating treatment with olanzapine but was associated with cognitive impairment
      as an adverse event.

PMID- 22367655
TI  - Computational prediction of state anxiety in Asian patients with cancer
      susceptible to chemotherapy-induced nausea and vomiting.
AB  - State anxiety, a risk factor for chemotherapy-induced nausea and vomiting (CINV),
      is a subjective symptom and difficult to quantify. Clinicians need appropriate
      anxiety measures to assess patients' risks of CINV. This study aimed to determine
      the anxiety characteristics that can predict CINV based on computational analysis
      of an objective assessment tool. A single-center, prospective, observational
      study was carried out between January 2007 and July 2010. Patients with breast,
      head and neck, and gastrointestinal cancers were recruited and treated with a
      variety of chemotherapy protocols and appropriate antiemetics. Chemotherapy
      induced nausea and vomiting characteristics and antiemetic use were recorded
      using a standardized diary, whereas patients' anxiety characteristics were
      evaluated using the Beck Anxiety Inventory. Principal component (PC) analysis was
      performed to analyze the anxiety characteristics. A subset known as principal
      variables, which had the highest PC weightings, was identified for patients with
      and without complete response, complete protection, and complete control.
      Chemotherapy-induced nausea and vomiting events and anxiety characteristics of
      710 patients were collated; 51%, 30%, and 20% were on anthracycline-, oxaliplatin
      , and cisplatin-based therapies, respectively. Most patients suffered from
      delayed CINV, with decreasing proportions achieving complete response (58%),
      complete protection (42%), and complete control (27%). Seven symptoms (fear of
      dying, fear of the worst, unable to relax, hot/cold sweats, nervousness,
      faintness, numbness) were identified as potential CINV predictors. This study
      demonstrates the usefulness of PC analysis, an unsupervised machine learning
      technique, to identify 7 anxiety characteristics that are useful as clinical CINV
      predictors. Clinicians should be aware of these characteristics when assessing
      CINV in patients on emetogenic chemotherapies.

PMID- 22367656
TI  - Eicosapentaenoic acid interventions in schizophrenia: meta-analysis of
      randomized, placebo-controlled studies.
AB  - BACKGROUND: Omega-3 fatty acids, in particular, eicosapentaenoic acid (EPA) have
      been suggested as augmentation strategies in the treatment of schizophrenia and
      related psychosis. Published results are conflicting, and the antipsychotic
      efficacy of such augmentation strategies is not well established. METHODS: Double
      blind, randomized, placebo-controlled studies using purified or EPA-enriched oils
      in established schizophrenia were included in a meta-analysis. The effect size of
      EPA on psychotic symptoms was measured using Hedges' g. Publication bias was
      assessed with funnel plots and Egger's intercept. Heterogeneity was assessed with
      Q statistic and I index. Influence of moderators was assessed with meta
      regression analyses in Comprehensive Meta-analysis Software version 2. RESULTS:
      The database included 167 schizophrenic subjects under the placebo arm (mean age,
      37 [SD, 9.7] years; 37% females) matched with 168 schizophrenic subjects under
      the EPA arm (mean age, 37 [SD, 7.9] years; 36% females) (t tests P > 0.05). Meta
      analysis showed no consistent significant effect for the EPA augmentation on
      psychotic symptoms (Hedges' g = 0.242; 95% confidence interval, 0.028-0.512, Z =
      1.7531, P > 0.05). There were no significant effects for moderator variables such
      as age, sex, and EPA dose used in the trials. Heterogeneity across studies was
      small and statistically non significant (Q = 9.06; P = 0.170; I = 33.81).
      CONCLUSIONS: Meta-analysis of randomized controlled trials on symptomatic outcome
      revealed no beneficial effect of EPA augmentation in established schizophrenia.
      However, no conclusion can be made for medium- to long-term effects of EPA in
      schizophrenia, in particular on relapse prevention in the early course of
      psychotic disorders.

PMID- 22367657
TI  - The anticonvulsant levetiracetam potentiates alcohol consumption in non-treatment
      seeking alcohol abusers.
AB  - BACKGROUND: Levetiracetam (Keppra) is a commonly prescribed anticonvulsant that
      has been shown to attenuate alcohol consumption in an open-label study of
      treatment-seeking, alcohol-dependent subjects. METHODS: Here we performed a 42
      day placebo-controlled, double-blind, randomized crossover trial to evaluate the
      effects of levetiracetam on moderate to heavy drinkers receiving either a low
      (500-1000 g/d) or a moderate (1000-2000 g/d) dose. Electronic diaries were used
      to monitor daily ethanol intake. RESULTS: Across the entire group, there was no
      effect of levetiracetam on drinking irrespective of dose, treatment order, family
      history, ethnicity, sex, or adverse effects. However, a median split of the data
      based on the number of drinks consumed while taking placebo revealed that
      levetiracetam significantly increased drinking in the lower drinking subjects (n
      = 23, P = 0.05, t = 2.07) while having no effect on drinking in the higher half
      (n = 23, P = 0.75, t = 0.32). Preliminary stratification based on common
      polymorphisms associated with alcoholism and impulsivity indicated that subjects
      with alcoholism-associated alleles may drink even more while taking
      levetiracetam. CONCLUSIONS: Our data suggest that levetiracetam is not an
      appropriate treatment for non-treatment seeking alcohol abusers and can, in fact,
      increase their consumption of alcohol.

PMID- 22367658
TI  - Different effects of the selective serotonin reuptake inhibitors fluvoxamine,
      paroxetine, and sertraline on the pharmacokinetics of fexofenadine in healthy
      volunteers.
AB  - Although the interaction between selective serotonin reuptake inhibitors (SSRIs)
      and other drugs is important in the treatment of depression, there have been few
      studies of SSRIs concerning transporter-mediated interactions in humans. The
      objective of this study was to evaluate the in vivo effects of commonly used
      SSRIs on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate.Twelve
      healthy volunteers (3 females and 9 males) were enrolled in this study. Each
      subject received a 60-mg dose of fexofenadine orally at baseline. Afterward, they
      were randomly assigned to receive 3 treatments with a 60-mg dose of fexofenadine
      after a 7-day treatment with fluvoxamine (50 mg/d), paroxetine (20 mg/d), or
      sertraline (50 mg/d), with 2-week intervals between the agents.Fluvoxamine
      pretreatment significantly increased the maximum plasma concentration, the area
      under the concentration time curves, and the 24-hour urinary fexofenadine
      excretion by 66% (P = 0.004), 78% (P = 0.029), and 78% (P < 0.001), respectively,
      without prolonging its elimination half-life. Paroxetine extended the elimination
      half-life of fexofenadine by 45% (P = 0.042), and it increased the 24-hour
      urinary fexofenadine excretion by 55% (P = 0.002). Sertraline did not alter any
      of the pharmacokinetic parameters of fexofenadine.This is the first report of the
      different effects of 3 commonly used SSRIs on fexofenadine pharmacokinetics in
      humans. Our 7-day, repeated-dose clinical study in healthy volunteers indicates
      that fluvoxamine and paroxetine, but not sertraline, may impact the patient
      exposure to fexofenadine, which is likely the result of P-glycoprotein inhibition
      in the small intestine and/or the liver.

PMID- 22367659
TI  - Augmenting clozapine with sertindole: a double-blind, randomized, placebo
      controlled study.
AB  - Clozapine augmentation with antipsychotic drugs is widely used despite sparse
      evidence supporting this strategy. Sertindole is a nonsedating atypical
      antipsychotic drug with low affinity for cholinergic receptors, which makes it
      potentially suitable for augmentation of clozapine. The study design was a 12
      week, double-blind, randomized, placebo-controlled study including patients with
      International Statistical Classification of Diseases, 10th Revision schizophrenia
      (F20.0-F20.3) and treated with clozapine for at least 6 months who had not
      achieved sufficient response. Patients were randomized 1:1 to either sertindole
      16 mg or placebo, and assessment was done at baseline and after 6 and 12 weeks.
      Assessment included the Positive and Negative Syndrome Scale, Clinical Global
      Impression, Udvalg for Kliniske Undersogelser, World Health Organization Quality
      of Life Brief, Drug Attitude Inventory, fasting glucose, lipids, and
      electrocardiogram. Clozapine augmentation with sertindole was not superior to
      placebo regarding total score or subscale score of the Positive and Negative
      Syndrome Scale, Clinical Global Impression, World Health Organization Quality of
      Life Brief, or Drug Attitude Inventory. No increased adverse effects compared
      with placebo were found. Four patients randomized to sertindole experienced a
      significant worsening of psychosis, and 2 of them required psychiatric admission.
      Metabolic parameters were unchanged during the study, but augmentation of
      clozapine with sertindole was associated with a 12-millisecond (SD, 20
      millisecond) QTc prolongation compared with 0 millisecond (SD, 20 milliseconds)
      in the placebo group (P < 0.03). Augmentation with sertindole showed no benefits
      compared with placebo. Psychiatrists should be aware that augmentation might not
      add any benefits for the patients and in some cases worsen psychosis.

PMID- 22367660
TI  - Pregnancy outcome after exposure to antidepressants and the role of maternal
      depression: results from the Norwegian Mother and Child Cohort Study.
AB  - Results of previous studies on the safety of antidepressants during pregnancy
      have been conflicting. The primary objective of this study was to investigate
      whether first-trimester exposure to antidepressants, specifically selective
      serotonin reuptake inhibitors (SSRIs), was associated with increased risk of
      congenital malformations. The secondary objective was to examine the effects of
      exposure to antidepressants during pregnancy on birth weight and gestational
      age.We included 63,395 women from the Norwegian Mother and Child Cohort Study.
      The women had completed 2 self-administered questionnaires at gestational weeks
      17 and 30 on medication use and medical, sociodemographic, and psychological
      factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry
      of Norway.Of the 63,395 women, 699 (1.1%) reported using antidepressants during
      pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first
      trimester was not associated with increased risk of congenital malformations in
      general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81-1.84)
      or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67-3.43). Exposure
      to antidepressants during pregnancy was not associated with increased risk of
      preterm birth (adjusted OR, 1.21; 95% CI, 0.87-1.69) or low birth weight
      (adjusted OR, 0.62; 95% CI, 0.33-1.16).This study does not suggest a strongly
      increased risk of malformations, preterm birth, or low birth weight following
      prenatal exposure to antidepressants. Without adjustments for level of maternal
      depression and various sociodemographic and lifestyle factors, antidepressant use
      during pregnancy would wrongly have been associated with an increased risk of
      preterm birth.

PMID- 22367661
TI  - Evidence-based medicine versus personalized medicine: are they enemies?

PMID- 22367662
TI  - High-dose baclofen for treatment-resistant alcohol dependence.
AB  - Alcohol dependence is associated with a wide array of physical and psychiatric
      complications and is a major cause of morbidity and mortality worldwide. Recent
      randomized trials of baclofen, with a total daily dose 30 mg administered in 3
      divided doses, have supported its efficacy in reducing craving and promoting
      abstinence from alcohol. Individual case studies support a possible increased
      effect at higher doses for treatment-resistant patients. Here, we report on 4
      alcohol-dependent patients resistant to standard treatments who responded to
      higher doses of baclofen ranging from 75 to 125 mg daily. Further research into
      the use of high-dose baclofen for treatment-resistant alcohol dependence is
      warranted.

PMID- 22367663
TI  - The psychopharmacology of aggressive behavior:  a translational approach: part 2:
      clinical studies using atypical antipsychotics, anticonvulsants, and lithium.
AB  - Patients experiencing mental disorders are at an elevated risk for developing
      aggressive behavior. In the past 10 years, the psychopharmacological treatment of
      aggression has changed dramatically owing to the introduction of atypical
      antipsychotics on the market and the increased use of anticonvulsants and lithium
      in the treatment of aggressive patients.This review (second of 2 parts) uses a
      translational medicine approach to examine the neurobiology of aggression,
      discussing the major neurotransmitter systems implicated in its pathogenesis
      (serotonin, glutamate, norepinephrine, dopamine, and gamma-aminobutyric acid) and
      the neuropharmacological rationale for using atypical antipsychotics,
      anticonvulsants, and lithium in the therapeutics of aggressive behavior. A
      critical review of all clinical trials using atypical antipsychotics
      (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone,
      ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate,
      lamotrigine, and gabapentin), and lithium are presented. Given the complex,
      multifaceted nature of aggression, a multifunctional combined therapy, targeting
      different receptors, seems to be the best strategy for treating aggressive
      behavior. This therapeutic strategy is supported by translational studies and a
      few human studies, even if additional randomized, double-blind, clinical trials
      are needed to confirm the clinical efficacy of this framework.

PMID- 22367664
TI  - Long-acting methylphenidate reduces collision rates of young adult drivers with
      attention-deficit/hyperactivity disorder.
AB  - This study investigated whether methylphenidate delivered through a long-acting
      transdermal system (MTS) would reduce collision rates of young adult drivers with
      attention-deficit/hyperactivity disorder (ADHD).Seventeen young adults completing
      the study (mean [SD] age, 20.82 [2.40] years; 14 men and 13 white) met the
      following inclusion criteria: ADHD diagnoses but not routinely taking ADHD
      medication, previously responsive to ADHD medication, active drivers with more
      than 1 collision or citation in the past 2 years, and no significant
      comorbidities. In this open-labeled, crossover design drivers were randomly
      assigned either to the no-medication condition for 3 months and then MTS for 3
      months or to the reverse sequence. In-car video monitoring of routine driving
      occurred during these 6 months. At baseline and after each condition,
      participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment
      of Risky Driving Scale, and their blood pressure, heart rate, and body weight
      were monitored.Compared with the no-medication condition, participants in the MTS
      condition self-reported fewer total ADHD (P < 0.04) and inattentive symptoms (P =
      0.014) and a trend for risky driving behaviors (P = 0.059) and had fewer video
      recorded collisions (P < 0.005) and other problematic driving events. There were
      no significant changes in blood pressure, heart rate, or body weight across
      conditions or any significant skin reactions to the MTS patch.This is the first
      study demonstrating that long-acting methylphenidate improves activities of daily
      living among young adults with ADHD. Specifically, methylphenidate improved
      safety in routine driving while reducing ADHD symptoms with minimal adverse
      effects.

PMID- 22367665
TI  - Genetic variation of Fusarium oxysporum isolates forming fumonisin B(1) and
      moniliformin.
AB  - Thirty single-spore isolates of a toxigenic fungus, Fusarium oxysporum, were
      isolated from asparagus spears and identified by species-specific polymerase
      chain reaction (PCR) and translation elongation factor 1-alpha (TEF) sequence
      analysis. In the examined sets of F. oxysporum isolates, the DNA sequences of
      mating type genes (MAT) were identified. The distribution of MAT idiomorph may
      suggest that MAT1-2 is a predominant mating type in the F. oxysporum population.
      F. oxysporum is mainly recognised as a producer of moniliformin-the highly toxic
      secondary metabolite. Moniliformin content was determined by high-performance
      liquid chromatography (HPLC) analysis in the range 0.05-1,007.47 MUg g(-1) (mean
      115.93 MUg g(-1)) but, also, fumonisin B(1) was detected, in the concentration
      range 0.01-0.91 MUg g(-1) (mean 0.19 MUg g(-1)). There was no association between
      mating types and the mycotoxins biosynthesis level. Additionally, a significant
      intra-species genetic diversity was revealed and molecular markers associated
      with toxins biosynthesis were identified.

PMID- 22367666
TI  - A phenotype map for 14q32.3 terminal deletions.
AB  - Detailed molecular-cytogenetic studies combined with thorough clinical
      characterization are needed to establish genotype-phenotype correlations for
      specific chromosome deletion syndromes. Although many patients with subtelomeric
      deletions have been reported, the phenotype maps for many of the corresponding
      syndromes, including the terminal deletion 14q syndrome, are only slowly
      emerging. Here, we report on five patients with terminal partial monosomy of
      14q32.3 and characteristic features of terminal deletion 14q syndrome. Four of
      the patients carry de novo terminal deletions of 14q, three of which have not yet
      been reported. One patient carries an unbalanced translocation
      der(14)t(9;14)(q34.3;q32.3). Minimum deletion sizes as determined by molecular
      karyotyping and FISH are 5.82, 5.56, 4.17, 3.54, and 3.29 Mb, respectively. Based
      on our findings and a comprehensive review of the literature, we refine the
      phenotype map for typical clinical findings of the terminal deletion 14q syndrome
      (i.e., intellectual disability/developmental delay, muscular hypotonia, postnatal
      growth retardation, microcephaly, congenital heart defects, genitourinary
      malformations, ocular coloboma, and several dysmorphic signs). Combining this
      phenotype map with benign copy-number variation data available from the Database
      of Genomic Variants, we propose a small region critical for certain features of
      the terminal deletion 14q syndrome which contains only seven RefSeq genes.

PMID- 22367667
TI  - Pathways to depression care: help-seeking experiences of low-income Latinos with
      diabetes and depression.
AB  - This qualitative study examines help-seeking pathways to depression care of low
      income Latinos with diabetes and major depression. A purposive sample (N = 19) of
      Spanish-speaking, immigrant, low-income Latinos was selected from a randomized
      clinical trial targeting Latinos with diabetes and major depression. Four focus
      groups followed by 10 in-depth qualitative interviews were conducted. Narratives
      were analyzed using the constant comparative method informed by grounded theory.
      Need for formal care was described in relation to acute somatic symptoms,
      functional impairment, and mood changes. Treatment initiation occurred through
      family members and primary care physicians who encouraged or inhibited help
      seeking. Adherence to depression care focused on interpersonal aspects of care,
      evaluated symptom relief, and improved functioning. Help-seeking barriers
      included self-reliance, language barriers, stigma, competing health demands, and
      structural barriers. Findings from this study highlight potential points of
      intervention for developing culturally-appropriate collaborative care approaches
      for low-income Latinos with diabetes and major depression.

PMID- 22367668
TI  - The mediating role of parent-child bonding to prevent adolescent alcohol abuse
      among Asian American families.
AB  - The purpose of this paper is to describe unique culturally-based factors that may
      increase the vulnerability of Asian American adolescents to engage in alcohol use
      and abuse and the role of parent-child bonding as a protective factor. In
      particular, this paper addresses the interactions among acculturation, alcohol
      use, and parent-child bonding and the challenges Asian American families face in
      strengthening parent-child bonds. We begin by examining likely causes for
      alienation that occur as a result of immigration to the United States. We then
      present the cultural context of Asian American families that can also serve to
      create distance between parent and child, including the contrasting cultural
      orientations of individualism and collectivism, Asian traditional values,
      differences in Eastern and Western parenting styles, and intergenerational
      cultural dissonance. Next, we present a review of the research that has examined
      acculturation as a risk factor for alcohol use and abuse among Asian American
      adolescents, with special attention to the mediating role of parent-child
      bonding. Finally, we conclude with recommendations for future research on the
      risk and protective factors for adolescent substance abuse, as well as other
      risky health behaviors among the growing population of Asian Americans in the
      United States.

PMID- 22367669
TI  - First trimester screening for aneuploidies in successive pregnancies:
      correlations between markers.
AB  - OBJECTIVES: Screening for chromosomal abnormalities in the first trimester of
      pregnancy is based on maternal age, nuchal translucency (NT), and biochemical
      markers (pregnancy-associated plasma protein-A and free beta human chorionic
      gonadotrophin). We have assessed the influence of screenings and outcomes in
      previous pregnancies on screenings in subsequent pregnancies. METHODS:
      Retrospective study of the correlation between the variables of first trimester
      combined screening for chromosome abnormalities in patients with subsequent
      pregnancies. Excluded were gestations with fetal aneuploidies. RESULTS: Between
      July 1999 and December 2009, there were 2291 women with more than 1 euploid
      pregnancy screened in the first trimester in our hospital. There was a moderate
      correlation for pregnancy-associated plasma protein-A (rho = 0.530, p <0.001) and
      free beta human chorionic gonadotrophin (rho = 0.439, p <0.001) between the first
      and second pregnancy. The trend continued in successive pregnancies. NT showed no
      correlations of clinical importance. With an overall false positive (FP) rate of
      2.1% for the combined screening, the probability of having a recurrent FP in the
      second pregnancy was 4.3% (not significant). CONCLUSION: There are significant
      correlations between biochemical markers but not NT in successive pregnancies,
      leading to increased risk of recurrence of FP results. However, such increase is
      not statistically significant if the overall FP rate is very low.

PMID- 22367670
TI  - A qualitative investigation of the decision-making process of couples considering
      prenatal screening for Down syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate how couples regard screening
      information and how they make subsequent decisions about undergoing prenatal
      screening for Down syndrome. METHODS: Twenty semi-structured interviews were
      conducted to explore aspects of the decision-making process. Interviews were
      digitally recorded and transcribed verbatim, and data were analysed using the
      framework approach. RESULTS: Couples reported a strong desire for a joint but
      ultimately private decision-making process and saw the main role of their midwife
      as an information provider. Considerable confusion existed over which screening
      tests were available via the National Health Service and which were offered
      privately. Provision of experiential information regarding both subsequent
      diagnostic tests and the experience of living with Down syndrome would have been
      beneficial. CONCLUSION: This study shows that couples would benefit from
      receiving experiential information when they are deciding about Down syndrome
      screening. Future research should be conducted to establish what form such
      information should take, the most helpful means to provide such information, and
      whether such information would also be useful in other contexts where people need
      to make decisions whether to undergo screening.

PMID- 22367671
TI  - Early first-trimester free-beta-hCG and PAPP-A serum distributions in
      monochorionic and dichorionic twins.
AB  - OBJECTIVE: To examine the distribution of first-trimester biochemical markers of
      aneuploidy in twins according to chorionicity. METHODS: Maternal serum free-beta
      human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A
      (PAPP-A) were measured between 8-13 + 6 weeks as a part of a routine first
      trimester screening program in conjunction with fetal nuchal translucency
      measured at 11 to 13 + 6 weeks' gestation. Data from 279 twin pregnancies were
      extracted from our fetal databases. Down syndrome cases were excluded. Individual
      marker concentrations were expressed as weight, ethnicity, smoking and maternal
      diabetes corrected. To compare the distributions of the biochemical parameters, a
      generalized additive model was used adjusted to a smoothing regression model with
      the values transformed with base 10'' logarithm using R software (generalized
      additive model-smoothing spline regression). RESULTS: Free-beta-hCG and PAPP-A
      distributions, analyzed with a generalized additive model adjusted to a smoothing
      regression model, were significantly different depending on the chorionicity. We
      graphically displayed the relationship between the predicted concentration of the
      free-beta-hCG and PAPP-A and the gestational age in days for monochorionic and
      dichorionic twins adjusted by weight. CONCLUSION: Pregnancy-associated plasma
      protein A and free-beta-hCG values are gestational age specific. It is necessary
      to make a distinction between monochorionic and dichorionic twins because
      biochemical markers are lower in monochorionic than in dichorionic twins.

PMID- 22367672
TI  - Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound
      findings as potential signs of nemaline myopathy.
AB  - OBJECTIVE: To increase awareness to the possibility of nemaline myopathy (NM)
      when abnormal prenatal ultrasound findings appear together with a carrier state
      for the common exon 55 deletion in the nebulin gene (NEB) of an Ashkenazi Jewish
      parent. METHODS: We describe four unrelated pregnancies with abnormal prenatal
      ultrasound findings resulting in the birth of newborns with NM, where one or both
      parents were of Ashkenazi Jewish origin. Data was collected retrospectively from
      the patients' medical files. Molecular analysis of NEB was performed on the DNA
      from the patients and parents. RESULTS: Prenatal ultrasound findings included
      polyhydramnios, decreased fetal movements, club feet, and arthrogryposis. A
      biopsy from two of the newborns was consistent with NM. In all of the newborns,
      the common NEB exon 55 deletion was detected in the heterozygote state and in
      three of them, a second novel mutation was found. CONCLUSIONS: Ultrasonographic
      findings suggestive of a myopathy and a carrier state for the NEB exon 55
      deletion in one of the parents should trigger a thorough investigation for NM.
      The extreme size of NEB imposes great difficulties when searching for a second
      mutation, especially under the time constraints of an ongoing pregnancy.

PMID- 22367673
TI  - Posterior fossa anomalies diagnosed with fetal MRI: associated anomalies and
      neurodevelopmental outcomes.
AB  - OBJECTIVE: The purpose of this study was to describe the relationship between
      intracranial and extracranial anomalies and neurodevelopmental outcome for
      fetuses diagnosed with a posterior fossa anomaly (PFA) on fetal MRI. METHODS:
      Cases of Dandy-Walker malformation, vermian hypogenesis/hypoplasia, and mega
      cisterna magna (MCM) were identified through the Fetal Care Center of Cincinnati
      between January 2004 and December 2010. Parental interview and retrospective
      chart review were used to assess neurodevelopmental outcome. RESULTS: Posterior
      fossa anomalies were identified in 59 fetuses; 9 with Dandy-Walker malformation,
      36 with vermian hypogenesis/hypoplasia, and 14 with MCM. Cases with isolated PFAs
      (14/59) had better outcomes than those with additional anomalies (p = 0.00016),
      with isolated cases of MCM all being neurodevelopmentally normal. Cases with
      additional intracranial anomalies had a worse outcome than those without
      intracranial anomalies (p = 0.00017). The presence of extracranial anomalies
      increased the likelihood of having a poor outcome (p = 0.00014) as did the
      identification of an abnormal brainstem (p = 0.00018). CONCLUSION: Intracranial
      and extracranial anomalies were good predictors of neurodevelopmental outcome in
      this study. The prognosis was poor for individuals with an abnormal brainstem,
      whereas those with isolated MCM had normal neurodevelopmental outcome.

PMID- 22367674
TI  - Noninvasive fetal RHD genotyping in the first trimester of pregnancy.

PMID- 22367675
TI  - Prenatal screening, social policy, and distribution of resources--striking a
      balance.

PMID- 22367676
TI  - Lysyl oxidase and enhancement of cell proliferation and angiogenesis in oral
      squamous cell carcinoma.
AB  - BACKGROUND: Lysyl oxidase (LOX) is a copper-dependent enzyme that cross-links
      collagen and elastin in the extracellular matrix. LOX overexpressed in various
      tumors. The manner in which LOX affects tumor growth remains controversial.
      METHODS: Chemical treatment and gene transfection were used to induce LOX
      overexpression or inhibition in cell lines SAS and SVEC4-10. LOX mRNA, protein,
      and activity were confirmed before tube formation assay and tumorigenesis. The
      microvessels in the tumor section were detected by immunostaining CD31-positive
      endothelial cells. RESULTS: LOX overexpression and copper induction of LOX
      activity increased SVEC4-10 tube formation. LOX silencing and beta
      aminopropionitrile inhibition of LOX activity had opposite effects. LOX
      overexpression increased proliferation and proliferating cell nuclear antigen
      expression. High LOX expression clones increased tumor size in a tumorigenesis
      model. The microvascular numbers were higher in LOX overexpression tumors than in
      control tumors. CONCLUSION: LOX can induce cell proliferation and angiogenesis in
      oral squamous cell carcinoma.

PMID- 22367677
TI  - Ovarian toxicity induced by dietary cadmium in hen.
AB  - To investigate the toxicity of cadmium (Cd) on female reproduction in birds, this
      study was conducted to determine the changes in biochemical parameters of serum
      and ovary tissue caused by dietary cadmium in hens. Ninety 50-day-old hyline
      white hens were randomly divided into three groups (30 hens per group): a control
      group was fed with basal diet, a low dose group was fed with basal diet
      containing 140 mg/kg CdCl(2) and a high dose group was fed with basal diet
      containing 210 mg/kg CdCl2. After being treated with Cd for 20, 40 and 60 days,
      ovary and serum samples were collected and examined for Cd content, histological
      evaluations, malondialdehyde (MDA) content, glutathione peroxidase (GPx) content,
      activities of superoxide dismutase (SOD), nitric oxide (NO) content, nitric oxide
      synthase (NOS) activity, and serum estradiol and progestogen levels. The results
      showed that the content of Cd, MDA, NO and the activity of NOS in ovary and serum
      were increased (P < 0.05), while the level of GPx and the activity of SOD were
      decreased (P < 0.05) in low dose and high dose groups. A time- and dose-dependent
      correlation was observed between serum and ovary tissue cadmium levels. The
      number of apoptotic cells in the ovary was increased in the Cd treatment group (P
      < 0.05). Extensive damage was observed in the ovary. The level of estradiol and
      progestogen in the serum of low dose and high dose groups was decreased
      significantly (P < 0.05). It indicated that Cd exposure resulted in oxidative
      damage of hens' ovary tissue by altering antioxidant defense enzyme systems,
      lipid peroxidation, apoptosis and endocrine disturbance which may be possible
      underlying reproductive toxicity mechanisms induced by Cd.

PMID- 22367678
TI  - Human dedifferentiated adipocytes show similar properties to bone marrow-derived
      mesenchymal stem cells.
AB  - Mature adipocytes are generally considered terminally differentiated because they
      have lost their proliferative abilities. Here, we studied the gene expression and
      functional properties of mature adipocytes isolated from human omental and
      subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in
      culture and their morphologies and functional changes with respect to mature
      adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs)
      and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell
      and reprogramming genes. They replicated in culture after assuming a fibroblast
      like shape and expanded similarly to SVF- and BM-derived MSCs. During the
      dedifferentiation process, mature adipocytes lost their lineage gene expression
      profile, assumed the typical mesenchymal morphology and immunophenotype,
      expressed stem cell genes and differentiated into multilineage cells. Moreover,
      during the dedifferentiation process, we showed changes in the epigenetic status
      of mature adipocytes, which led dedifferentiated adipocytes to display a similar
      DNA methylation condition to BM-derived MSCs. Like SVF- and BM-derived MSCs,
      dedifferentiated adipocytes were able to inhibit the proliferation of stimulated
      lymphocytes in coculture while mature adipocytes stimulated their growth.
      Furthermore, dedifferentiated adipocytes maintained the survival and complete
      differentiation characteristic of hematopoietic stem cells. This is the first
      study that in addition to characterizing isolated and dedifferentiated adipocytes
      also reports on the immunoregulatory and hematopoietic supporting functions of
      these cells. This structural and functional characterization might have clinical
      applications of both mature and dedifferentiated adipocytes in such fields, as
      regenerative medicine.

PMID- 22367680
TI  - Effect of lanthanide ions on dynamic nuclear polarization enhancement and liquid
      state T1 relaxation.
AB  - In the dynamic nuclear polarization process, microwave irradiation facilitates
      exchange of polarization from a radical's unpaired electron to nuclear spins at
      cryogenic temperatures, increasing polarization by >10,000. Doping samples with
      Gd(3+) ions further increases the achievable solid-state polarization. However,
      on dissolution, paramagnetic lanthanide metals can be potent relaxation agents,
      decreasing liquid-state polarization. Here, the effects of lanthanide metals on
      the solid and liquid-state magnetic properties of [1-(13)C]pyruvate are studied.
      The results show that in addition to gadolinium, holmium increases not only the
      achievable polarization but also the rate of polarization. Liquid-state
      relaxation studies found that unlike gadolinium, holmium minimally affects T(1).
      Additionally, results reveal that linear contrast agents dissociate in pyruvic
      acid, greatly reducing liquid-state T(1). Although macrocyclic agents do not
      readily dissociate, they yield lower solid-state polarization. Results indicate
      that polarization with free lanthanides and subsequent chelation during
      dissolution produces the highest polarization enhancement while minimizing liquid
      state relaxation.

PMID- 22367679
TI  - Roles of activated microglia in hypoxia induced neuroinflammation in the
      developing brain and the retina.
AB  - Amoeboid microglial cells (AMCs) in the developing brain display surface
      receptors and antigens shared by the monocyte-derived tissue macrophages.
      Activation of AMCs in the perinatal brain has been associated with
      periventricular white matter damage in hypoxic-ischemic conditions. The
      periventricular white matter, where the AMCs preponderate, is selectively
      vulnerable to hypoxia as manifested by death of premyelinating oligodendrocytes
      and degeneration of axons leading to neonatal mortality and long-term
      neurodevelopmental deficits. AMCs respond vigorously to hypoxia by producing
      excess amounts of inflammatory cytokines e.g. the tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta) along with glutamate, nitric oxide
      (NO) and reactive oxygen species which collectively cause oligodendrocyte death,
      axonal degeneration as well as disruption of the immature blood brain barrier. A
      similar phenomenon is observed in the hypoxic developing cerebellum in which
      activated AMCs induced Purkinje neuronal death through production of TNF-alpha
      and IL-1beta via their respective receptors. Hypoxia is also implicated in
      retinopathy of prematurity in which activation of AMCs has been shown to cause
      retinal ganglion cell death through production of TNF-alpha and IL-1beta and NO.
      Because AMCs play a pivotal role in hypoxic injuries in the developing brain
      affecting both neurons and oligodendrocytes, a fuller understanding of the
      underlying molecular mechanisms of microglial activation under such conditions
      would be desirable for designing of a novel therapeutic strategy for management
      of hypoxic damage.

PMID- 22367681
TI  - Clinical dimensions of fibromyalgia symptoms and development of a combined index
      of severity: the CODI index.
AB  - BACKGROUND: Although a large body of work indicates that fibromyalgia (FM) is not
      a discrete entity, few studies have attempted to classify the heterogeneity of FM
      symptoms. The objectives of the present study were to confirm the existence of
      two latent dimensions underlying FM symptoms (Core-FM symptoms and Distress) by
      means of factor analysis techniques, and to develop and validate a new combined
      index of symptom severity (the CODI). METHODS: We analyzed and combined the
      baseline scores on six visual analog scales of the FIQ (pain, general fatigue,
      morning fatigue, stiffness, anxiety, and depression) and on the STAI-T (trait
      anxiety) of 216 Spanish patients diagnosed with FM (97.7% women) who were
      participating in a randomized, controlled trial. RESULTS: The principal component
      analysis indicated the presence of two correlated factors (labeled as Core-FM
      symptoms and Distress) that explained 64% of total variance. The subsequent
      confirmatory factor analysis yielded more empirical support for the two-factor
      model than the one-factor model (all items loading on one latent dimension). The
      two factors possessed adequate internal consistency and construct validity given
      the pattern of significant correlations with the Euroqol items. The Core-FM
      dimension had a stronger relationship with mobility, self-care, usual activities,
      and pain/discomfort than with anxiety/depression, whereas the Distress dimension
      showed the opposite pattern. Finally, summing the standardized scores of the two
      dimensions, a new combined index of symptom severity (the CODI) was developed.
      CONCLUSION: The clinical implications and utility of the CODI are discussed in
      relation to previous research on FM.

PMID- 22367682
TI  - A cross-cultural validation of patient-reported outcomes measures: a study of
      breast cancers survivors.
AB  - PURPOSE: Psychometric inadequacy interferes with the assessment of patient
      reported health outcomes. This study examined the psychometric properties of
      several standardized measures in health research. METHODS: Participants completed
      health outcomes measures including the FACT-G, SF-36, MOS Social Support Survey,
      and CES-D. Psychometric properties examined include reliability, and construct
      and concurrent validity. RESULTS: 320 BCS including 88 African-, 95 English
      proficient Latina-, and 137 Limited English-proficient Latina-Americans
      participated. The findings demonstrate acceptable reliability (alpha > 0.70) and
      consistent factor structures for most measures with the variance ranging from 56
      to 84%. The FACT-G physical well-being and SF-36 role limitations subscales had
      the best fitting structures. Concurrent validity showed the FACT-G subscales
      correlated with their appropriate counterparts. CONCLUSIONS: Despite being
      commonly used instruments in HRQOL (e.g., FACT-G, SF-36) and QOL (e.g., CES-D,
      MOS) research, few studies reported the psychometric properties of these and when
      applied cross-culturally. However, evaluating the psychometric properties of
      measures in health outcomes research should be done routinely.

PMID- 22367683
TI  - Report of a rare and aggressive case of oral malignant melanoma.
AB  - BACKGROUND: Oral melanoma is a very rare malignancy with unknown etiology. Its
      higher incidence is between 41 and 60 years of age. A high localization of oral
      melanoma was found in the maxilla. Gender distribution was reported as 1:1. Oral
      melanoma represents 0.2% to 8% of the all the total cases of melanoma of the
      body. CASE REPORT: In this article we report an aggressive case of oral melanoma
      in a 71-year-old male with chief complaint of black swelling of the gingiva,
      paresthesia, and denture ill fitting. DISCUSSION: Most oral melanomas are
      asymptomatic and painless in early stages and unfortunately diagnosis delayed
      until symptoms occurred. Early detection of suspected melanotic lesions by
      patient, dentist, and physician is very important.

PMID- 22367684
TI  - Mesoporous bioactive glass as a multifunctional system for bone regeneration and
      controlled drug release.
AB  - PURPOSE: Coupling the potential for bone regeneration and the ability for in situ
      controlled drug release in a single device is a challenging field of research in
      bone tissue engineering; in an attempt to pursue this aim, mesoporous bioactive
      glass (MBG) membranes belonging to the SiO2-P2O5-CaO ternary system were produced
      and characterized. METHODS: The glass was synthesized via a sol-gel route coupled
      with an evaporation-induced self-assembly process by using a non-ionic block co
      polymer as a mesostructure former. MBG structure and morphology, as well as
      mesopores size and shape, were investigated by x-ray diffraction, transmission
      electron microscopy, and N2 adsorption-desorption measurements. In vitro
      bioactivity was investigated by soaking MBG membranes in simulated body fluid
      (SBF) for different time frames. Ibuprofen was encapsulated into MBG pores and
      drug release kinetics in SBF were assessed. Biological tests by using SAOS-2
      cells were performed to assess the material cytocompatibility. RESULTS: The
      material revealed significant ability to induce hydroxyapatite formation on its
      surface (bioactivity). Drug release kinetics in SBF are very similar to those
      obtained for mesoporous silica having mesopore size comparable to that of the
      prepared MBG (~5 nm). No evidence of cell viability depression was detected
      during in vitro culture, which demonstrates the good biological compatibility of
      the material. CONCLUSIONS: The easiness of tailoring and shaping, the highly
      bioactive and biocompatible behavior, and the drug uptake/release ability of the
      prepared materials may suggest their use as "smart" multifunctional grafts for
      bone reconstructive surgery.

PMID- 22367686
TI  - Quantitative analysis of upper limbs during gait: a marker set protocol.
AB  - PURPOSE: to develop a marker set for simultaneously assessing upper and lower
      limb biomechanics during gait. METHODS: 24 healthy young subjects (mean age:
      23.80 years) were assessed quantitatively using an optoelectronic system, two
      force platform and a video system. Passive markers were positioned according to
      the proposed marker set which enables acquiring the upper and lower limb movement
      simultaneously during Gait Analysis. In addition to the traditional parameters
      obtained from Gait Analysis, the shoulder and elbow angles were computed from
      markers coordinates of upper limbs; then, some significant parameters were
      identified and calculated. From shoulder and elbow position, angles, angular
      velocities, angular acceleration, moments, and powers were calculated for
      shoulder and elbow joints. RESULTS: Kinematic and kinetic data were obtained in
      the three planes (sagittal, frontal, and transversal) for the shoulder and in the
      sagittal plane for the elbow. Normative ranges were obtained for these parameters
      from data of healthy participants. CONCLUSIONS: The proposed experimental set-up
      enables simultaneous assessment of upper and lower limb movement during gait.
      Thus, no further trials are required in addition to those acquired during
      standard gait analysis in order to assess upper limb motion, which also makes the
      experimental set-up feasible for clinical applications.

PMID- 22367687
TI  - Dissolution medium responsive simvastatin release from biodegradable apatite
      cements and the therapeutic effect in osteoporosis rats.
AB  - Bio-convertible artificial bone with slow release of anti-osteoporosis drug is
      useful to treat osteoporosis. Apatite cement containing 6% simvastatin (APD) had
      lower crystallinity than natural bone. In-vitro drug release tests in simulated
      body fluid (pH 7.8) and acetate buffer (pH 4.5) were performed at 37.0 C as
      physical models of osteoblast and osteoclast conditions (SOB and SOC). The device
      had lower drug release rate under SOB, but significantly higher rates under SOC. 
      The simvastatin release rate changed depending on dissolution media, it repeated
      twice, and the rate under SOC was 15 times higher than under SOB. The device
      showed dissolution medium responsive drug release.  After implantation of the APD
      in osteoporosis rats, the bone mineral density was evaluated by the x-ray
      computed tomography.  The result indicated that the bone mineral density of APD
      implanted rat was significantly higher than that of control diseased.  The result
      indicated that the device was therapeutically useful to bone regeneration.

PMID- 22367688
TI  - Distribution, elimination, and biopersistence to 90 days of a systemically
      introduced 30 nm ceria-engineered nanomaterial in rats.
AB  - Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit
      manufacture, and is being pursued as an antioxidant therapeutic. Our objective is
      to extend previous findings showing that there were no reductions of cerium in
      organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days
      after a single nanoscale ceria administration. An ~5% aqueous dispersion of
      citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or
      vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside
      observations were obtained daily, body weight weekly. Daily urinary and fecal
      cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples
      collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for
      cerium determination. Histology and oxidative stress were assessed. Less than 1%
      of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight
      gain was initially impaired. Spleen weight was significantly increased in some
      ceria-treated groups, associated with abnormalities. Ceria was primarily retained
      in the spleen, liver, and bone marrow. There was little decrease of ceria in any
      tissue over the 90 days. Granulomas were observed in the liver. Time-dependent
      oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was
      persistently retained by organs of the mononuclear phagocyte system, associated
      with adverse changes. The results support concern about the long-term fate and
      adverse effects of inert nanoscale metal oxides that distribute throughout the
      body, are persistently retained, and produce adverse changes.

PMID- 22367690
TI  - Gas-phase chemistry of benzyl cations in dissociation of N-benzylammonium and N
      benzyliminium ions studied by mass spectrometry.
AB  - In this study, the fragmentation reactions of various N-benzylammonium and N
      benzyliminium ions were investigated by electrospray ionization mass
      spectrometry. In general, the dissociation of N-benzylated cations generates
      benzyl cations easily. Formation of ion/neutral complex intermediates consisting
      of the benzyl cations and the neutral fragments was observed. The intra-complex
      reactions included electrophilic aromatic substitution, hydride transfer,
      electron transfer, proton transfer, and nucleophilic aromatic substitution. These
      five types of reactions almost covered all the potential reactivities of benzyl
      cations in chemical reactions. Benzyl cations are well-known as Lewis acid and
      electrophile in reactions, but the present study showed that the gas-phase
      reactivities of some suitably ring-substituted benzyl cations were far richer.
      The 4-methylbenzyl cation was found to react as a Bronsted acid, benzyl cations
      bearing a strong electron-withdrawing group were found to react as electron
      acceptors, and para-halogen-substituted benzyl cations could react as substrates
      for nucleophilic attack at the phenyl ring. The reactions of benzyl cations were
      also related to the neutral counterparts. For example, in electron transfer
      reaction, the neutral counterpart should have low ionization energy and in
      nucleophilic aromatic substitution reaction, the neutral counterpart should be
      piperazine or analogues. This study provided a panoramic view of the reactions of
      benzyl cations with neutral N-containing species in the gas phase.

PMID- 22367689
TI  - Histone deacetylase 6 associates with ribosomes and regulates de novo protein
      translation during arsenite stress.
AB  - Histone deacetylase 6 (HDAC6) is known as a cytoplasmic enzyme that regulates
      cell migration, cell adhesion, and degradation of misfolded proteins by
      deacetylating substrates such as alpha-tubulin and Hsp90. When HaCaT
      keratinocytes were exposed to 1-200MUM sodium arsenite, we observed perinuclear
      localization of HDAC6 within 30 min. Although the overall level of HDAC6 protein
      did not change, sodium arsenite caused an increase of HDAC6 in ribosomal
      fractions. Separation of ribosomal subunits versus intact ribosomes or polysomes
      indicated that HDAC6 was mainly detected in 40/43S fractions containing the small
      ribosomal subunit in untreated cells but was associated with 40/43S and 60/80S
      ribosomal fractions in arsenite-treated cells. Immunocytochemistry studies
      revealed that arsenite caused colocalization of HDAC6 with the ribosomal large
      and small subunit protein L36a and S6. Both L36a and S6 were detected in the
      immunocomplex of HDAC6 isolated from arsenite-treated cells. The observed
      physical interaction of HDAC6 with ribosomes pointed to a role of HDAC6 in stress
      induced protein translation. Among arsenite stress-induced proteins, de novo Nrf2
      protein translation was inhibited by Tubastatin A. These data demonstrate that
      HDAC6 was recruited to ribosomes, physically interacted with ribosomal proteins,
      and regulated de novo protein translation in keratinocytes responding to arsenite
      stress.

PMID- 22367691
TI  - Alternative reliable method for cytochrome P450 2D6 poor metabolizers genotyping.
AB  - High-resolution melting curve analysis (HRM) of polymerase chain reaction (PCR)
      amplicons has been described as a fast, cheap, and reliable closed-tube method of
      genotyping with no need for labeled primers or labeled probes. We adapted this
      melting analysis assay for the detection of the most common nonfunctional alleles
      of cytochrome P-450 (CYP) 2D6 in the Caucasian population that affect the
      metabolism of many commonly used drugs. We used this method to genotype 91
      patients under paroxetine therapy. The presence and the constitution of the most
      common single-nucleotide polymorphisms (1846G>A, 2988G>A, 100C>T, 2549delA,
      2615_2617delAAG, and 1707delT) in poor and intermediate metabolizers from the
      Caucasian population were detected in short amplicons (<=148 bp). After
      fluorescence normalization, the wild-type, homozygous, and heterozygous samples
      were easily distinguishable from each other by their specific melting curve
      shape. A total of 92.6% of the 1846G>A heterozygotes, 96% of the 100C>T
      heterozygotes, and 100% of the 2988G>A, 2549delA, 2615_2617delAAG, and 1707delT
      heterozygotes have been correctly distinguished from the wild types. One hundred
      percent of all the homozygotes in this group of patients have been detected
      without any error. HRM of short amplicons is a simple tool for effective, rapid,
      and reliable CYP2D6 genotyping that does not require real-time PCR, labeled
      probes, processing or any separations after PCR. The reaction is performed in a
      closed-tube system and is highly specific and sensitive. We proved that this
      technique is highly reliable for use in routine diagnostics.

PMID- 22367692
TI  - Molecular analysis of drought tolerance in tea by cDNA-AFLP based transcript
      profiling.
AB  - A cDNA-AFLP approach was used to identify transcript and/or genes specifically
      expressed in response to drought in tea. Drought was artificially induced and
      whole genome transcript profiling was done at three different stages-6 days
      before wilting, 3 days before wilting and at wilting stage of both tolerant and
      susceptible cultivars, and genetic differences was thus visualized as
      polymorphisms in the transcriptome. The cDNA-AFLP technique allowed genes and
      transcripts to be identified in the tolerant genotype (TV-23) whose expression is
      responsive to drought stress. The cluster analysis revealed two types of
      clustering-type I separated the tolerant and susceptible cultivar, whereas type
      II separated the time point of sample and this may be grouped as early and late
      responsive transcripts. 108 transcript derived fragments were identified as
      differentially expressed in tolerant genotypes of which 89 sequences could be
      obtained. Fifty-nine of them showed homology in the public databases. Functional
      ontology showed genes related to carbohydrate metabolism, response to stress,
      protein modification process and translation. Cluster I includes five fragments
      and cluster II includes 25 fragments. Other genes strongly expressed in response
      to drought in tolerant genotype would help us in identifying and determining the
      genetic basis of mechanisms involved in conferring drought tolerance in tea.

PMID- 22367693
TI  - A Hollywood mystery: the untimely death of Jean Harlow.

PMID- 22367694
TI  - Infliximab therapy for inflammatory discitis in ankylosing spondylitis.

PMID- 22367695
TI  - Prepatellar and preolecranon subcutaneous calcifications in scleroderma.

PMID- 22367696
TI  - Paraneoplastic palmar fasciitis in carcinoma breast.

PMID- 22367698
TI  - Central nervous system tuberculosis: mimicking neuropsychiatric systemic lupus
      erythematosus.

PMID- 22367699
TI  - Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and
      lung cancer risk in the NIH-AARP Diet and Health Study Cohort.
AB  - PURPOSE: Previous studies have reported that lung cancer risk may be decreased,
      increased, or unaffected by prior use of menopausal hormone therapy (MHT).
      METHODS: To assess this issue further, we examined relationships among 118,008
      women, ages 50-71 years who were recruited during 1995-1996 for the NIH-AARP Diet
      and Health Study and in whom 2,097 incident lung carcinomas were identified
      during follow-up through 2006. Multivariable Cox proportional hazards models
      estimated relative risks (RR) and 95% confidence intervals (CIs) associated with
      various measures of self-reported MHT use. RESULTS: We found no evidence that
      either estrogen therapy (ET)-only or estrogen plus progestin therapy (EPT) use
      was substantially related to subsequent lung cancer risk (respective RRs and 95%
      CIs for ever use = 0.97, 0.86-1.09 and 1.03, 0.90-1.17). There were no
      significant variations according to currency or duration of use of either
      formulation, nor was there evidence that risks varied within subgroups defined by
      cigarette smoking or body size. The absence of effect was seen for nearly all
      lung cancer subtypes, with the exception of an increased risk of
      undifferentiated/large cell cancers associated with long-term ET-only use (p
      (trend) = 0.02), a relationship not observed among EPT users. CONCLUSIONS: Our
      results failed to support any substantial alterations in lung cancer risk
      associated with use of either unopposed estrogen or estrogen plus progestin MHT,
      even when detailed exposure measures and other risk predictors were considered.

PMID- 22367700
TI  - The nicotine dependence phenotype, time to first cigarette, and larynx cancer
      risk.
AB  - PURPOSE: Cigarette smoking is the major cause of laryngeal cancer. The time to
      first cigarette after waking in the morning is a behavior associated with several
      dimensions of nicotine dependence including the dose of smoke uptake. We
      hypothesized that a short TTFC increases the risk of laryngeal cancer. METHODS:
      The analysis was based on data from a hospital-based case-control study of
      laryngeal cancer. The current analysis included only subjects who were ever
      cigarette smokers, including 570 cases and 343 controls (832 whites and 81
      blacks). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using
      unconditional logistic regression adjusting for smoking history and other
      potential confounders. Incidence data from the Surveillance, Epidemiology, and
      End Results (SEER) Program of the National Cancer Institute from 1975 to 2006
      were analyzed for trends in laryngeal cancer. RESULTS: There was a dose-response
      relationship between TTFC and supraglottic cancer. Compared to subjects who
      smoked more than 60 min after waking, the adjusted odds ratio was 1.51 (95% CI,
      0.63-3.61) for 30-60 min and 3.13 (95% CI, 1.56-6.30) for 0-30 min. No
      association was observed between TTFC and cancer of the glottis. In blacks, the
      TTFC was not associated with the risk of laryngeal cancer. Trends in SEER rates
      were similar for cancer of the glottis and supraglottis, indicating that the site
      specific differences were not affected by unknown confounders. CONCLUSION: A
      nicotine dependence behavior that is associated with cigarette smoke uptake
      increases the risk of cancer of the supraglottis larynx, but not glottis larynx.

PMID- 22367701
TI  - Body fat distribution and breast cancer risk: findings from the Nigerian breast
      cancer study.
AB  - PURPOSE: The relationship between overall obesity and breast cancer risk has been
      well recognized, but the role of central obesity in breast cancer development is
      uncertain. METHODS: Between 1998 and 2009, 1,233 invasive breast cancer cases and
      1,101 community controls were recruited into the Nigerian Breast Cancer Study at
      Ibadan, Nigeria. Logistic regressions were used to calculate multivariate odds
      ratio (OR) and 95% confidence intervals (CI), adjusting for age, body mass index
      (BMI), and other known risk factors for breast cancer. RESULTS: The OR for the
      highest quartile group of waist circumference relative to the lowest was 2.39
      (95% CI, 1.59-3.60; P-trend < 0.001). Comparing women with waist/hip ratio (WHR)
      in the lowest quartile group, the OR for women in the highest quartile category
      was 2.15 (95% CI, 1.61-2.85; P-trend < 0.001). An inverse association was
      observed between hip circumference and breast cancer, with an OR of 0.36 for the
      highest quartile (95% CI, 0.24-0.55; P-trend < 0.001). The effects of these three
      measures existed in both pre- and postmenopausal women. Of note, we found a
      significant interaction between WHR and BMI (P-interaction = 0.016): the OR
      comparing the highest to the lowest WHR quartile was 2.81 (95% CI, 1.90-4.16) for
      women with BMI < 25 kg/m2 and 1.70 (95% CI, 1.11-2.61) for women with BMI >= 25
      kg/m2. CONCLUSIONS: These results suggest that central adiposity, measured by
      waist circumference and waist/hip ratio, was an important risk factor for breast
      cancer in Nigerian women, and the effect of central adiposity was strong in
      normal-weight women.

PMID- 22367703
TI  - Study on mineral elements in Salvia roborwskii from the Qinghai-Tibet Plateau.
AB  - The contents of trace elements, including aluminum, barium, beryllium, calcium,
      cobaltium, chromium, copper, iron, potassium, lanthanum, lithium, magnesium,
      manganese, sodium, nickel, phosphorus, lead, sulfur, silicon, titanium, vanadium,
      and zinc, were determined by ICP-AES. The mean concentrations of the 22 elements
      were as follows: K>Ca>Mg>Fe>Al>Na>S>P>Ba>Ti>Mn>Zn>Sr>Cu>Ni=Cr>Pb>V>Li=La>Co>Be.
      Principal components analysis of SPSS was applied to study the characteristic
      elements in Salvia roborwskii. Five principal components which accounted for
      89.288% of the total variance were extracted from the original data. The first
      factor accounted for 56.401% of the total variance, which meant that aluminum,
      barium, beryllium, calcium, and cobaltium were the characteristic elements in S.
      roborwskii. This useful new method was used to evaluate the quality of S.
      roborwskii, and to provide the scientific foundation for its utilization and
      further research.

PMID- 22367702
TI  - Early postoperative epidermal growth factor receptor inhibition: safety and
      effectiveness in inhibiting microscopic residual of oral squamous cell carcinoma
      in vivo.
AB  - BACKGROUND: The local-regional failure of advanced oral squamous cell carcinoma
      (OSCC) after surgery results from the regrowth of residual tumor cells that may
      be stimulated by epidermal growth factor receptor (EGFR) ligands during the wound
      healing process. METHODS: The level of EGFR ligands in human drain fluids (DFs)
      from OSCC resection and remote flap donor site were determined. A mouse model of
      microscopic residual OSCC was established and treated with cetuximab to measure
      tumor growth, survival, and cervical lymph node metastases. A mouse model of
      wound healing was also established to assess the effect of an EGFR antibody on
      the wound healing process. RESULTS: EGFR ligands are found in sites from OSCC
      resection. EGFR targeted therapy can delay tumor regrowth in a microscopic
      residual disease model of OSCC without significant effects on local wound
      healing. CONCLUSION: These results provide a strong rationale for clinical
      evaluation of this approach to treat patients with local-regionally advanced
      OSCC.

PMID- 22367704
TI  - Effect of copper on the expression of IGF-1 from chondrocytes in newborn piglets
      in vitro.
AB  - The experiment was performed to evaluate the influence of copper supplementation
      on insulin-like growth factor-1 (IGF-1) mRNA expression in chondrocytes of
      newborn pigs. Chondrocytes were isolated and cultured in media containing 15%
      fetal calf serum supplemented with 0, 15.6, 31.2, and 62.5 MUmol/L copper in 90
      mm culture plate. After 0, 12, 24, and 48 h, total RNA was isolated from
      chondrocytes. Then, IGF-1 mRNA expression was determined by semiquantitative RT
      PCR. The results showed that the expression of IGF-1 mRNA, adjusted for beta
      actin expression, was increased in the culture media added to 15.6, 31.2, and
      62.5 MUmol/L copper, respectively. In the present experiment, the optimal copper
      concentration and optimal culture time for the expression of IGF-1 mRNA were 31.2
      MUmol/L and 48 h, respectively.

PMID- 22367705
TI  - Pharmacokinetics, tissue distribution, and plasma protein binding study of
      platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats
      and dogs by ICP-MS.
AB  - Dicycloplatin, as a new antitumor supramolecule, was considered to have higher
      solubility and higher stability compared with carboplatin. The aim of the present
      study was to evaluate the pharmacokinetic characteristics of platinum originating
      from dicycloplatin. A rapid, sensitive, and specific method with inductively
      coupled plasma mass spectrometry (ICP-MS) has been developed for the
      determination of platinum in bio-samples. The study was performed in male rats
      and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous
      injection. Pharmacokinetic parameters were calculated by non-compartmental
      method, and the dose of platinum was used in the calculation of these parameters.
      Results showed that plasma concentrations of platinum began to decrease rapidly
      initially but decline slowly with a long terminal phase. The mean half-life was
      27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs
      separately. Tissue distribution showed that platinum originating from
      dicycloplatin had a certain distribution in testis and prostate. Plasma protein
      binding proportion of platinum was increased with time. In conclusion, this
      research investigated the pharmacokinetic characteristics including plasma
      kinetics, tissue distribution, and plasma protein binding of platinum originating
      from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.

PMID- 22367706
TI  - Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or
      as an alternative to preoperative chemoradiation?
AB  - BACKGROUND: For patients with resectable rectal cancer chemoradiation (CRT) or
      short-course preoperative radiotherapy (SCPRT) reduces locoregional failure,
      without extending disease-free survival (DFS) or overall survival (OS).
      Compliance to postoperative adjuvant chemotherapy is poor. Neoadjuvant
      chemotherapy (NACT) offers an alternative strategy. METHODS: A systematic
      computerised database search identified studies exploring NACT alone or NACT
      preceding/succeeding radiation. The primary outcome measure was pathological
      complete response (pCR). Secondary outcome measures included acute toxicity,
      surgical morbidity, circumferential resection margin, locoregional failure, DFS
      and OS. RESULTS: Four case reports, 12 phase I/II studies, 4 randomised phase II
      and one randomised phase III study evaluated chemotherapy before CRT. Four
      prospective studies reviewed chemotherapy after CRT. Three phase II studies
      investigated chemotherapy using FOLFOX plus bevacizumab without radiotherapy. In
      24 studies of 1271 patients, pCR varied from 7% to 36%, but with no impact on
      metastatic disease. CONCLUSIONS: NACT before CRT delivers does not compromise CRT
      but has not increased pCR rates, R0 resection rate, improved DFS or reduced
      metastases. NACT following CRT is an interesting strategy, and the utility of
      NACT alone could be explored compared with SCPRT or CRT in selected patients with
      rectal cancer where the impact of radiotherapy on DFS and OS is marginal.

PMID- 22367707
TI  - Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type
      biliary tract cancer.
AB  - BACKGROUND: Combination chemotherapy has proven beneficial in biliary tract
      cancer and further improvements may be achieved by individualizing treatment
      based on biomarkers and by adding biological agents. We report the effect of
      chemotherapy with panitumumab as first-line therapy for KRAS wild-type
      irresectable biliary tract cancer. PATIENTS AND METHODS: Patients were treated
      with gemcitabine 1000 mg/m(2), oxaliplatin 60 mg/m(2), and panitumumab 6 mg/kg
      i.v. every 2 weeks followed by two daily administrations of capecitabine 1000
      mg/m(2) in 7 days. RESULTS: During 22 months, 46 patients were included in a
      single institution. The primary end point, fraction of progression-free survival
      (PFS) at 6 months, was 31/42 [74%; 95% confidence interval (CI) 58% to 84%].
      Forty-two patients had measurable disease. Response rate was 33% and disease
      control rate 86%. Median PFS was 8.3 months (95% CI 6.7-8.7 months) and median
      overall survival was 10.0 months (95% CI 7.4-12.7 months). Toxicity was
      manageable including eight cases of epidermal growth factor receptor-related skin
      adverse events of grade 2 or more. CONCLUSIONS: Marker-driven patient selection
      is feasible in the systemic treatment of biliary tract cancer. Combination
      chemotherapy with panitumumab in patients with KRAS wild-type tumors met the
      efficacy criteria for future testing in a randomized trial.

PMID- 22367708
TI  - Liver phospholipid transfer protein (PLTP) expression with a PLTP-null background
      promotes very low-density lipoprotein production in mice.
AB  - It is known that plasma phospholipid transfer protein (PLTP) activity influences
      lipoprotein metabolism. The liver is one of the major sites of lipoprotein
      production and degradation, as well as of PLTP expression. To address the impact
      of liver-expressed PLTP on lipoprotein metabolism, we created a mouse model that
      expresses PLTP in the liver acutely and specifically, with a PLTP-null
      background. This approach in mouse model preparations can also be used
      universally for evaluating the function of many other genes in the liver. We
      found that liver PLTP expression dramatically increases plasma levels of non-high
      density lipoprotein (HDL) cholesterol (2.7-fold, P < 0.0001), non-HDL
      phospholipid (2.5-fold, P < 0.001), and triglyceride (51%, P < 0.01), but has no
      significant influence on plasma HDL lipids compared with controls. Plasma
      apolipoprotein (apo)B levels were also significantly increased in PLTP-expressing
      mice (2.2-fold, P < 0.001), but those of apoA-I were not. To explore the
      mechanism involved, we examined the lipidation and secretion of nascent very low
      density lipoprotein (VLDL), finding that liver PLTP expression significantly
      increases VLDL lipidation in hepatocyte microsomal lumina, and also VLDL
      secretion into the plasma. CONCLUSION: It is possible to prepare a mouse model
      that expresses the gene of interest only in the liver, but not in other tissues.
      Our results suggest, for the first time, that the major function of liver PLTP is
      to drive VLDL production and makes a small contribution to plasma PLTP activity.

PMID- 22367710
TI  - The impact of age stereotypes on self-perceptions of aging across the adult
      lifespan.
AB  - OBJECTIVES: Individuals' perceptions of their own age(ing) are important
      correlates of well-being and health. The goals of the present study were to (a)
      examine indicators of self-perceptions of aging across adulthood and (b)
      experimentally test whether age stereotypes influence self-perceptions of aging.
      METHOD: Adults 18-92 years of age were presented with positive, negative, or no
      age stereotypes. Before and after the stereotype activation, aging satisfaction
      and subjective age were measured. RESULTS: The activation of positive age
      stereotypes did not positively influence self-perceptions of aging. Quite the
      contrary, priming middle-aged and older adults in good health with positive age
      stereotypes made them feel older. After the activation of negative age
      stereotypes, older adults in good health felt older and those in bad health
      wanted to be younger than before the priming. Even younger and middle-aged adults
      reported younger desired ages after the negative age stereotype priming. Persons
      in bad health also thought they looked older after being primed with negative age
      stereotypes. DISCUSSION: Taken together, although we find some support for
      contrast effects, most of our results can be interpreted in terms of assimilation
      effects, suggesting that individuals integrate stereotypical information into
      their self-evaluations of age(ing) when confronted with stereotypes.

PMID- 22367709
TI  - Age invariance in feeling of knowing during implicit interference effects.
AB  - OBJECTIVES: Prior research found age invariance in accuracy of delayed judgments
      of learning accuracy (Eakin, D. K., & Hertzog, C. [2006]. Release from implicit
      interference in memory and metamemory: Older adults know that they can't let go.
      The Journals of Gerontology, Series B: Psychological Sciences and Social
      Sciences, 61, 340-347). We tested whether aging affects accuracy of feeling of
      knowing (FOK) predictions under implicit interference. Discrepancies in the
      literature suggest that FOKs sometimes are and sometimes are not affected by
      aging. In addition, because the effects of implicit interference are different on
      recognition than on recall, older adults may have difficulty ignoring the impact
      of interference on recall in order to accurately predict the lack of interference
      effects on recognition. METHOD: Younger and older adults studied cue-target pairs
      and cue set size varied. After a cued recall test, they made FOKs about future
      recognition of the target given the cue and then took a recognition test.
      RESULTS: Neither younger nor older adults were able to predict recognition of
      unrecalled items. FOKs were more correlated with recall than with recognition for
      both age groups. Although both recall and recognition varied with age, no age
      differences were obtained in FOK accuracy. DISCUSSION: FOK accuracy was not
      impaired with age, even when memory was. FOKs of both younger and older adults
      reflected implicit interference effects in recall, not recognition.

PMID- 22367711
TI  - Words have consequences.

PMID- 22367713
TI  - Robustness of personality and affect relations under chronic conditions: the case
      of age-related vision and hearing impairment.
AB  - OBJECTIVES: Relations between personality and affect are generally regarded as
      robust. Extraversion is closely linked to positive affect (PA), but not to
      negative affect (NA), whereas neuroticism is closely linked to NA, but not to PA.
      We argue in this work that the stress experience associated with age-related
      vision and hearing impairment may alter this commonly found pattern as compared
      with sensory unimpaired (UI) older adults. METHOD: We analyzed data from a sample
      of severely visually impaired (VI; N = 121), severely hearing impaired (HI; N =
      116), and a control condition of sensory UI (grand age mean: 82 years; N = 150).
      RESULTS: Based on a structural equation modeling approach, we found that the
      relationship between extraversion and PA was higher in the UI as compared with
      the sensory impaired groups. In contrast, the strong linkage between neuroticism
      and NA was not affected by sensory status. Furthermore, we observed a meaningful
      negative relation between extraversion and NA only in the VI group. DISCUSSION:
      Findings support the argument that the relationship between personality and
      affect deserves qualification when chronic vision and hearing impairment is
      present.

PMID- 22367712
TI  - Neuroticism combined with slower and more variable reaction time: synergistic
      risk factors for 7-year cognitive decline in females.
AB  - OBJECTIVE: Among adults, slower and more variable reaction times are associated
      with worse cognitive function and increased mortality risk. Therefore, it is
      important to elucidate risk factors for reaction time change over the life
      course.  Method.  Data from the Health and Lifestyle Survey (HALS) were used to
      examine predictors of 7-year decline in reaction time (N = 4,260). Regression
      derived factor scores were used to summarize general change across 4 reaction
      time variables: simple mean, 4-choice mean, simple variability, and 4-choice
      variability (53.52% of variance). RESULTS: Age (B = .02, p < .001) and HALS1
      baseline reaction time (B = -.10, p = .001) were significant risk factors for
      males (N = 1,899). In addition to these variables, in females (N = 2,361),
      neuroticism was significant and interacted synergistically with baseline reaction
      time (B = .06, p = .04). Adjustment for physiological variables explained the
      interaction with neuroticism, suggesting that candidate mechanisms had been
      identified.  Discussion.  A priority for future research is to replicate
      interactions between personality and reaction time in other samples and find
      specific mechanisms. Stratification of population data on cognitive health by
      personality and reaction time could improve strategies for identifying those at
      greater risk of cognitive decline.

PMID- 22367714
TI  - Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184
      in embryonic corneal lineage specification.
AB  - Approximately 6 million people worldwide are suffering from severe visual
      impairments or blindness due to corneal diseases. Corneal allogeneic
      transplantation is often required to restore vision; however, shortage in corneal
      grafts and immunorejections remain major challenges. The molecular basis of
      corneal diseases is poorly understood largely due to lack of appropriate cellular
      models. Here, we described a robust differentiation of human-induced pluripotent
      stem cells (hiPSCs) derived from hair follicles or skin fibroblasts into corneal
      epithelial-like cells. We found that BMP4, coupled with corneal fibroblast
      derived conditioned medium and collagen IV allowed efficient corneal epithelial
      commitment of hiPSCs in a manner that recapitulated corneal epithelial lineage
      development with high purity. Organotypic reconstitution assays suggested the
      ability of these cells to stratify into a corneal-like epithelium. This model
      allowed us identifying miR-450b-5p as a molecular switch of Pax6, a major
      regulator of eye development. miR-450b-5p and Pax6 were reciprocally distributed
      at the presumptive epidermis and ocular surface, respectively. miR-450b-5p
      inhibited Pax6 expression and corneal epithelial fate in vitro, altogether,
      suggesting that by repressing Pax6, miR-450b-5p triggers epidermal specification
      of the ectoderm, while its absence allows ocular epithelial development.
      Additionally, miR-184 was detectable in early eye development and corneal
      epithelial differentiation of hiPSCs. The knockdown of miR-184 resulted in a
      decrease in Pax6 and K3, in line with recent findings showing that a point
      mutation in miR-184 leads to corneal dystrophy. Altogether, these data indicate
      that hiPSCs are valuable for modeling corneal development and may pave the way
      for future cell-based therapy.

PMID- 22367715
TI  - Free-breathing cardiac MR with a fixed navigator efficiency using adaptive gating
      window size.
AB  - A respiratory navigator with a fixed acceptance gating window is commonly used to
      reduce respiratory motion artifacts in cardiac MR. This approach prolongs the
      scan time and occasionally yields an incomplete dataset due to respiratory
      drifts. To address this issue, we propose an adaptive gating window approach in
      which the size and position of the gating window are changed adaptively during
      the acquisition based on the individual's breathing pattern. The adaptive gating
      window tracks the breathing pattern of the subject throughout the scan and adapts
      the size and position of the gating window such that the gating efficiency is
      always fixed at a constant value. To investigate the image quality and
      acquisition time, free breathing cardiac MRI, including both targeted coronary
      MRI and late gadolinium enhancement imaging, was performed in 67 subjects using
      the proposed navigator technique. Targeted coronary MRI was acquired from eleven
      healthy adult subjects using both the conventional and proposed adaptive gating
      window techniques. Fifty-six patients referred for cardiac MRI were also imaged
      using late gadolinium enhancement with the proposed adaptive gating window
      technique. Subjective and objective image assessments were used to evaluate the
      proposed method. The results demonstrate that the proposed technique allows free
      breathing cardiac MRI in a relatively fixed time without compromising imaging
      quality due to respiratory motion artifacts.

PMID- 22367716
TI  - Reducing methane emissions and the methanogen population in the rumen of Tibetan
      sheep by dietary supplementation with coconut oil.
AB  - The objective was to evaluate the effect of dietary coconut oil on methane
      (CH(4)) emissions and the microbial community in Tibetan sheep. Twelve animals
      were assigned to receive either a control diet (oaten hay) or a mixture diet
      containing concentrate (maize meal), in which coconut oil was supplemented at 12
      g/day or not for a period of 4 weeks. CH(4) emissions were measured by using the
      'tunnel' technique, and microbial communities were examined using quantitative
      real-time PCR. Daily CH(4) production for the control and forage-to-concentrate
      ratio of 6:4 was 17.8 and 15.3 g, respectively. Coconut oil was particularly
      effective at reducing CH(4) emissions from Tibetan sheep. The inclusion of
      coconut oil for the control decreased CH(4) production (in grams per day) by
      61.2%. In addition, there was a positive correlation between the number of
      methanogens and the daily CH(4) production (R = 0.95, P < 0.001). Oaten hay diet
      containing maize meal (6:4) plus coconut oil supplemented at 12 g/day decreases
      the number of methanogens by 77% and a decreases in the ruminal fungal population
      (85-95%) and Fibrobacter succinogenes (50-98%) but an increase in Ruminococcus
      flavefaciens (25-70%). The results from our experiment suggest that adding
      coconut oil to the diet can reduce CH(4) emissions in Tibetan sheep and that
      these reductions persist for at least the 4-week feeding period.

PMID- 22367717
TI  - Translating the brain transcriptome in neuroAIDS: from non-human primates to
      humans.
AB  - In the post-human genome project era, high throughput techniques to detect and
      computational algorithms to analyze differentially expressed genes have proven to
      be powerful tools for studying pathogenesis of neuroAIDS. Concurrently, discovery
      of non-coding RNAs and their role in development and disease has underscored the
      importance of examining the entire transcriptome instead of protein coding genes
      alone. Herein, we review the documented changes in brain RNA expression profiles
      in the non-human primate model of neuroAIDS (SIV infected monkeys) and compare
      the findings to those resulting from studies in post-mortem human samples of
      neuroAIDS. Differential expression of mRNAs involved in inflammation and immune
      response are a common finding in both monkey and human samples - even in HIV
      infected people on combination antiretroviral therapy, a shared set of genes is
      upregulated in the brains of both infected monkeys and humans: B2M, IFI44, IFIT3,
      MX1, STAT1. Additionally, alterations in ion channel encoding genes have been
      observed in the human studies. Brain miRNA profiling has also been performed, and
      up-regulation of two miRNAs originating from the same transcript, miR-142-3p and
      miR-142-5p, is common to human and monkey neuroAIDS studies. With increases in
      knowledge about the genome and advances in technology, unraveling alterations in
      the transcriptome in the SIV/monkey model will continue to enrich our knowledge
      about the effects of HIV on the brain.

PMID- 22367718
TI  - Urinary tract infections and post-operative fever in percutaneous
      nephrolithotomy.
AB  - PURPOSE: To review the incidence of UTIs, post-operative fever, and risk factors
      for post-operative fever in PCNL patients. MATERIALS AND METHODS: Between 2007
      and 2009, consecutive PCNL patients were enrolled from 96 centers participating
      in the PCNL Global Study. Only data from patients with pre-operative urine
      samples and who received antibiotic prophylaxis were included. Pre-operative
      bladder urine culture and post-operative fever (>38.5 degrees C) were assessed.
      Relationship between various patient and operative factors and occurrence of post
      operative fever was assessed using logistic regression analyses. RESULTS: Eight
      hundred and sixty-five (16.2%) patients had a positive urine culture; Escherichia
      coli was the most common micro-organism found in urine of the 350 patients
      (6.5%). Of the patients with negative pre-operative urine cultures, 8.8%
      developed a fever post-PCNL, in contrast to 18.2% of patients with positive urine
      cultures. Fever developed more often among the patients whose urine cultures
      consisted of Gram-negative micro-organisms (19.4-23.8%) versus those with Gram
      positive micro-organisms (9.7-14.5%). Multivariate analysis indicated that a
      positive urine culture (odds ratio [OR] = 2.12, CI [1.69-2.65]), staghorn
      calculus (OR = 1.59, CI [1.28-1.96]), pre-operative nephrostomy (OR = 1.61, CI
      [1.19-2.17]), lower patient age (OR for each year of 0.99, CI [0.99-1.00]), and
      diabetes (OR = 1.38, CI [1.05-1.81]) all increased the risk of post-operative
      fever. Limitations include the use of fever as a predictor of systemic infection.
      CONCLUSIONS: Approximately 10% of PCNL-treated patients developed fever in the
      post-operative period despite receiving antibiotic prophylaxis. Risk of post
      operative fever increased in the presence of a positive urine bacterial culture,
      diabetes, staghorn calculi, and a pre-operative nephrostomy.

PMID- 22367720
TI  - Thermo-responsive non-woven scaffolds for "smart" 3D cell culture.
AB  - The thermo-responsive polymer poly(N-isopropylacrylamide) has received widespread
      attention for its in vitro application in the non-invasive, non-destructive
      release of adherent cells on two dimensional surfaces. In this study, 3D non
      woven scaffolds fabricated from poly(propylene) (PP), poly(ethylene
      terephthalate) (PET), and nylon that had been grafted with PNIPAAm were tested
      for their ability to support the proliferation and subsequent thermal release of
      HC04 and HepG2 hepatocytes. Hepatocyte viability and proliferation were estimated
      using the Alamar Blue assay and Hoechst 33258 total DNA quantification. The
      assays revealed that the pure and grafted non-woven scaffolds maintained the
      hepatocytes within the matrix and promoted 3D proliferation comparable to that of
      the commercially available AlgimatrixTM alginate scaffold. Albumin production and
      selected cytochrome P450 genes expression was found to be superior in cells
      growing on pure and grafted non-woven PP scaffolds as compared to cells grown as
      a 2D monolayer. Two scaffolds, namely, PP-g-PNIPAAm-A and PP-g-PNIPAAm-B were
      identified as having far superior thermal release capabilities; releasing the
      majority of the cells from the matrices within 2 h. This is the first report for
      the development of 3D non-woven, thermo-responsive scaffolds able to release
      cells from the matrix without the use of any enzymatic assistance or scaffold
      degradation.

PMID- 22367719
TI  - Lung endothelial ADAM17 regulates the acute inflammatory response to
      lipopolysaccharide.
AB  - Acute lung injury (ALI) is associated with increased vascular permeability,
      leukocyte recruitment, and pro-inflammatory mediator release. We investigated the
      role of the metalloproteinase ADAM17 in endotoxin-induced ALI with focus on
      endothelial ADAM17. In vitro, endotoxin-mediated induction of endothelial
      permeability and IL-8-induced transmigration of neutrophils through human
      microvascular endothelial cells required ADAM17 as shown by inhibition with
      GW280264X or shRNA-mediated knockdown. In vivo, ALI was induced by intranasal
      endotoxin-challenge combined with GW280264X treatment or endothelial adam17
      knockout. Endotoxin-triggered upregulation of ADAM17 mRNA in the lung was
      abrogated in knockout mice and associated with reduced ectodomain shedding of the
      junctional adhesion molecule JAM-A and the transmembrane chemokine CX3CL1.
      Induced vascular permeability, oedema formation, release of TNF-alpha and IL-6
      and pulmonary leukocyte recruitment were all markedly reduced by GW280264X or
      endothelial adam17-knockout. Intranasal application of TNF-alpha could not
      restore leukocyte recruitment and oedema formation in endothelial adam17-knockout
      animals. Thus, activation of endothelial ADAM17 promotes acute pulmonary
      inflammation in response to endotoxin by multiple endothelial shedding events
      most likely independently of endothelial TNF-alpha release leading to enhanced
      vascular permeability and leukocyte recruitment.

PMID- 22367722
TI  - Reducing global health inequities through tobacco control.

PMID- 22367721
TI  - Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer
      risk in three large nested case-control studies.
AB  - Few prospective studies have examined the associations between blood levels of
      folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR)
      polymorphisms, and colorectal cancer. We evaluated the associations between
      plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three large
      prospective studies: the Nurses' Health Study, the Health Professionals Follow-up
      Study, and the Physicians' Health Study. A total of 602 incident cases were
      identified and individually matched to controls who provided blood specimens. We
      used conditional logistic regression to calculate the relative risk (RR) and 95%
      confidence interval (95% CI) and then pooled the estimates using a random effects
      model. We found a lower risk of colorectal cancer among participants with low
      plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each
      successively higher quartile of plasma folate levels were 1.55 (1.14-2.11), 1.37
      (1.00-1.88), and 1.47 (1.07-2.01; P for trend = 0.10). For the MTHFR
      polymorphisms, RRs (95% CIs) were 0.62 (0.44-0.90) for 677TT versus CC/CT and
      0.68 (0.31-1.51) for 1298CC versus AC/AA, and these lower-risk genotypes were
      associated with lower circulating plasma folate levels. When we partitioned the
      variation in plasma folate levels, variation due to folate intake was not
      positively associated with colorectal cancer risk. We found that low plasma
      folate levels were associated with lower risk of colorectal cancer. The reasons
      underlying a lower risk of colorectal cancer with low plasma folate levels
      require elucidation because plasma folate levels can reflect dietary intake,
      genetic influences, and other factors.

PMID- 22367723
TI  - Global tobacco inequalities: a new frontier.

PMID- 22367725
TI  - Asthma and risk of brain cancer in children.
AB  - PURPOSE: Little is known about the causes of central nervous system tumors in
      children. An inverse association between asthma and brain cancer was found in
      adults, but there is a dearth of studies in children. The goal of this study was
      to evaluate the association between asthma and brain cancer in children. METHODS:
      Two hundred and seventy-two cases of children with brain tumor diagnosed between
      0 and 14 years of age in the Province of Quebec, Canada, between 1980 and 1999
      and 272 incidence density-matched controls were included in the study. The
      parents of cases and controls were interviewed by phone using structured
      questionnaires. Besides asthma in children, family history of asthma, the
      presence of other atopies, and medication intake were also investigated.
      Conditional logistic regression was used to analyze the data. RESULTS: Brain
      tumor risk was decreased in children with asthma (OR, 0.55; CI 95%, 0.33-0.93),
      with eczema (OR, 0.52; CI 95%, 0.17-1.57), and with both asthma and eczema (OR,
      0.76; CI 95%, 0.18-3.2). Maternal or sibling asthma did not modify the effect of
      asthma on central nervous system (CNS) tumors, while father's asthma seemed to
      increase the risk, but numbers were small. Antiasthma medications such as inhaled
      corticosteroid and beta agonists seemed to increase the risk of CNS tumors (OR
      for steroids, 2.55; CI 95%, 0.79-8.20 and OR for inhaled beta agonist, 1.62; CI
      95%, 0.57-4.63). CONCLUSIONS: This study strengthens the hypothesis of inverse
      association between asthma and brain cancer in children, but family history and
      medications for asthma need further investigation.

PMID- 22367724
TI  - Commentary: eight ways to prevent cancer: a framework for effective prevention
      messages for the public.
AB  - Research over the past 40 years has convincingly shown that lifestyle factors
      play a huge role in cancer incidence and mortality. The public, though, can often
      discount the preventability of cancer. That health information on the Internet is
      a vast and often scientifically suspect commodity makes promoting important and
      sound cancer prevention messages to the public even more difficult. To help
      address these issues and improve the public's knowledge of, and attitudes toward,
      cancer prevention, there need to be concerted efforts to create evidence-based,
      user-friendly information about behaviors that could greatly reduce overall
      cancer risk. Toward this end, we condensed the current scientific evidence on the
      topic into eight key behaviors. While not an end in themselves, "Eight Ways to
      Stay Healthy and Prevent Cancer" forms an evidence-based and targeted framework
      that supports broader cancer prevention efforts.

PMID- 22367726
TI  - Ultraviolet exposure and non-Hodgkin's lymphoma: beneficial and adverse effects?
AB  - Studies of risk of non-Hodgkin's lymphoma have found both direct and inverse
      correlations with respect to solar ultraviolet (UV) doses. Reduced risk is
      generally found in midlatitudes, while increased risk is generally found at
      higher latitudes. It is suggested that reduced risk arises from vitamin D
      production from UVB irradiance, while increased risk arises from
      immunosuppression associated with UVA irradiance. The ratio of UVA to UVB
      increases with increasing latitude.

PMID- 22367728
TI  - Sporadic endolymphatic sac tumor: its clinical, radiological, and histological
      features, management, and follow-up.
AB  - BACKGROUND: Sporadic endolymphatic sac tumor (ELST) is rare. We described the
      clinical, radiological, and histological features, treatment, and follow-up of
      ELST. METHOD: This was a retrospective analysis of 7 cases of sporadic ELST that
      were managed between 1993 and 2010. RESULTS: Twenty-five to 75 years was the age
      range of the patients. Subjective hearing loss and tinnitus were the most common
      presenting features. Five patients had total deafness and 2 had severe
      sensorineural hearing loss. The most common radiological feature was temporal
      bone destruction with tumor extension to cerebellopontine angle and posterior
      cranial fossa. Cholesterol or hemosiderin cysts around the tumor could be a
      characteristic feature. Major skull base procedures were performed in all 7
      cases, and complete tumor excision was achieved in 6 of them. One patient needed
      a second surgery after she was referred to us after an incomplete first surgery.
      Recurrences were detected in 2 patients during follow-up; 1 of them received
      irradiation without minimal change to the tumor size and the second refused any
      treatment for the recurrence. Both of them are alive with disease. CONCLUSION:
      Early detection and radical surgical excision at first attempt give best results.
      Radiotherapy could be considered only in unresectable recurrences.

PMID- 22367729
TI  - Estrogens and stroke:  disentangling a complex relationship.

PMID- 22367730
TI  - Hormone therapy and urinary incontinence.

PMID- 22367732
TI  - Terminal patients in Belgian nursing homes: a cost analysis.
AB  - Policy makers and health care payers are concerned about the costs of treating
      terminal patients. This study was done to measure the costs of treating terminal
      patients during the final month of life in a sample of Belgian nursing homes from
      the health care payer perspective. Also, this study compares the costs of
      palliative care with those of usual care. This multicenter, retrospective cohort
      study enrolled terminal patients from a representative sample of nursing homes.
      Health care costs included fixed nursing home costs, medical fees, pharmacy
      charges, other charges, and eventual hospitalization costs. Data sources
      consisted of accountancy and invoice data. The analysis calculated costs per
      patient during the final month of life at 2007/2008 prices. Nineteen nursing
      homes participated in the study, generating a total of 181 patients. Total mean
      nursing home costs amounted to 3,243 ? per patient during the final month of
      life. Total mean nursing home costs per patient of 3,822 ? for patients receiving
      usual care were higher than costs of 2,456 ? for patients receiving palliative
      care (p = 0.068). Higher costs of usual care were driven by higher
      hospitalization costs (p < 0.001). This study suggests that palliative care
      models in nursing homes need to be supported because such care models appear to
      be less expensive than usual care and because such care models are likely to
      better reflect the needs of terminal patients.

PMID- 22367733
TI  - Two siblings with Niemann-Pick disease (NPD) type B: clinical findings and novel
      mutations of the acid sphingomyelinase gene.
AB  - Acid sphingomyelinase deficiency leads to the accumulation of sphingomyelin in
      cells, causing Niemann-Pick disease (NPD) types A/B. RF (13.66 y) and HF (3 y)
      are brother and sister. RF growth was markedly delayed at the age of 12.66 y (123
      cm; -3.25 SD), while at the age 3 y his sister is 86 cm (-2.75 SD). The brother
      had a huge liver (13 cm) and spleen (12 cm). His sister also had an enlarged
      liver, but presented no other symptoms. The fibroblast cultivation had a reduced
      sphingomyelinase activity in the fibroblasts (0.68 mkat/kg protein), beta
      galaktosidase (937 mkat/kg) and glucosilceramidase (125.4 mkat/kg) were elevated.
      Mutational analysis demonstrated the siblings are compound heterozygotes (V112M
      and H554Y). The mother is carrier of V112M and the father carries H554Y. This is
      the first report of NPD type B in Macedonia. The novel mutation results in a
      moderately severe phenotype of NPD type B.

PMID- 22367734
TI  - Effect of microwave exposure on the ovarian development of Drosophila
      melanogaster.
AB  - In the present experiments the effect of GSM radiation on ovarian development of
      virgin Drosophila melanogaster female insects was studied. Newly emerged adult
      female flies were collected and divided into separate identical groups. After the
      a lapse of certain number of hours-different for each group-the insects (exposed
      and sham-exposed) were dissected and their intact ovaries were collected and
      photographed under an optical microscope with the same magnification. The size of
      the ovaries was compared between exposed and sham-exposed virgin female insects,
      during the time needed for the completion of oogenesis and maturation of the
      first eggs in the ovarioles. Immediately after the intact ovaries were
      photographed, they were further dissected into individual ovarioles and treated
      for TUNEL and acridine-orange assays to determine the degree of DNA damage in the
      egg chamber cells. The study showed that the ovarian size of the exposed insects
      is significantly smaller than that of the corresponding sham-exposed insects, due
      to destruction of egg chambers by the GSM radiation, after DNA damage and
      consequent cell death induction in the egg chamber cells of the virgin females as
      shown in previous experiments on inseminated females. The difference in ovarian
      size between sham-exposed and exposed virgin female flies becomes most evident 39
      45 h after eclosion when the first eggs within the ovaries are at the late
      vitellogenic and post-vitellogenic stages (mid-late oogenesis). More than 45 h
      after eclosion, the difference in ovarian size decreases, as the first mature
      eggs of the sham-exposed insects are leaving the ovaries and are laid.

PMID- 22367735
TI  - The Wnt/beta-catenin pathway regulates self-renewal of cancer stem-like cells in
      human gastric cancer.
AB  - Cancer stem cells (CSCs) possess the ability of self-renewal and tumor
      initiation. Targeting key signaling pathways that are active in CSC self-renewal
      is one approach to cancer therapy. Abnormal activation of the Wnt/beta-catenin
      pathway has been described in a wide variety of human cancers and in CSCs;
      however, the role of this pathway in gastric CSCs has not been reported. In our
      study, we investigated whether the Wnt/beta-catenin pathway plays an important
      role in gastric CSCs. First, we isolated cancer stem-like cells (CSLCs) from the
      human gastric cancer cell line MKN-45 using tumorsphere cultures. We tested
      whether tumorsphere cells were CSLCs using the following three criteria: i) We
      identified that the expression of the CSC marker CD44 was significantly greater
      in tumorsphere cells compared to adherent cells; ii) compared with adherent
      cells, the floating tumorsphere cells had greater self-renewing capacity; iii) in
      vivo xenograft studies showed that tumorsphere cells generate larger tumors than
      adherent cells at the same number. In addition, we studied the mechanism(s) by
      which the canonical Wnt signaling pathway acts in CSLCs. Western blotting and
      real-time PCR showed that the expression levels of beta-catenin and c-myc, cyclin
      d1 and axin 2 were downregulated/upregulated with the inhibition/activation of
      the Wnt pathway. The pathway blocked by DKK-1 caused a higher reduction in the
      self-renewing capacity of MKN-45 tumorsphere cells and the pathway activated by
      lithium chloride improved the self-renewal of CSLCs. In conclusion, our data
      suggested that the Wnt/beta-catenin pathway is essential for the self-renewal of
      CSLCs in human gastric cancer.

PMID- 22367731
TI  - The 2012 hormone therapy position statement of: The North American Menopause
      Society.
AB  - OBJECTIVE: This position statement aimed to update the evidence-based position
      statement published by The North American Menopause Society (NAMS) in 2010
      regarding recommendations for hormone therapy (HT) for postmenopausal women. This
      updated position statement further distinguishes the emerging differences in the
      therapeutic benefit-risk ratio between estrogen therapy (ET) and combined
      estrogen-progestogen therapy (EPT) at various ages and time intervals since
      menopause onset. METHODS: An Advisory Panel of expert clinicians and researchers
      in the field of women's health was enlisted to review the 2010 NAMS position
      statement, evaluate new evidence, and reach consensus on recommendations. The
      Panel's recommendations were reviewed and approved by the NAMS Board of Trustees
      as an official NAMS position statement. RESULTS: Current evidence supports the
      use of HT for perimenopausal and postmenopausal women when the balance of
      potential benefits and risks is favorable for the individual woman. This position
      statement reviews the effects of ET and EPT on many aspects of women's health and
      recognizes the greater safety profile associated with ET. CONCLUSIONS: Recent
      data support the initiation of HT around the time of menopause to treat menopause
      related symptoms and to prevent osteoporosis in women at high risk of fracture.
      The more favorable benefit-risk ratio for ET allows more flexibility in extending
      the duration of use compared with EPT, where the earlier appearance of increased
      breast cancer risk precludes a recommendation for use beyond 3 to 5 years.

PMID- 22367736
TI  - African swine fever among slaughter pigs in Mubende district, Uganda.
AB  - Owing to frequent reports of suspected outbreaks and the presence of reservoir
      hosts and vectors (warthogs, bushpigs and O. moubata ticks), African swine fever
      (ASF) is believed to be an endemic disease in Uganda. There have, however, been
      very few studies carried out to confirm its existence in Uganda. This study was
      carried out to describe the prevalence of ASF based on pathologic lesions and
      analysis of serum samples from slaughtered pigs during a suspected outbreak in
      the Mubende district of Uganda. The study was based on visits to 22
      slaughterhouses where individual pigs were randomly selected for a detailed ante
      mortem and post-mortem inspections. Sera were also collected for laboratory
      analysis. A total of 997 pigs (53.7% male and 46.3% female) were examined for
      lesions suggestive of ASF and sero-positivity of sera for ASF antibodies. The
      sera were tested using enzyme-linked immunosorbent assay (ELISA) and positive
      samples were further confirmed with an immunoblot assay. The results showed that
      3.8% (38/997) of the pigs examined had clinical signs and post-mortem lesions
      suggestive of ASF. Two of 997 (0.2%) sera analysed were positive for ASF
      antibodies. Of the sub-counties investigated, Bagezza (12%) and Kiyuni (11%) had
      the highest prevalence of lesions suggestive of ASF based on ante- and post
      mortem examination results, while Mubende town council (1.7%) had the lowest.
      This study found a low number of pigs (3.8%) with lesions suggestive of ASF at
      slaughter and an even lower number of pigs (0.2%) that were seropositive at
      slaughter, however a significantly higher number of pigs were slaughtered during
      the outbreak as a strategy for farmers to avoid losses associated with mortality.

PMID- 22367738
TI  - Kinetic differentiation between homo- and alternating AT DNA by sterically
      restricted phosphonium dyes.

PMID- 22367737
TI  - Atmospheric oxygen inhibits growth and differentiation of marrow-derived mouse
      mesenchymal stem cells via a p53-dependent mechanism: implications for long-term
      culture expansion.
AB  - Large scale expansion of human mesenchymal stem cells (MSCs) is routinely
      performed for clinical therapy. In contrast, developing protocols for large scale
      expansion of primary mouse MSCs has been more difficult due to unique aspects of
      rodent biology. Currently, established methods to isolate mouse MSCs select for
      rapidly dividing subpopulations that emerge from bone marrow cultures following
      long-term (months) expansion in atmospheric oxygen. Herein, we demonstrate that
      exposure to atmospheric oxygen rapidly induced p53, TOP2A, and BCL2-associated X
      protein (BAX) expression and mitochondrial reactive oxygen species (ROS)
      generation in primary mouse MSCs resulting in oxidative stress, reduced cell
      viability, and inhibition of cell proliferation. Alternatively, procurement and
      culture in 5% oxygen supported more prolific expansion of the CD45(-ve)
      /CD44(+ve) cell fraction in marrow, produced increased MSC yields following
      immunodepletion, and supported sustained MSC growth resulting in a 2,300-fold
      increase in cumulative cell yield by fourth passage. MSCs cultured in 5% oxygen
      also exhibited enhanced trilineage differentiation. The oxygen-induced stress
      response was dependent upon p53 since siRNA-mediated knockdown of p53 in wild
      type cells or exposure of p53(-/-) MSCs to atmospheric oxygen failed to induce
      ROS generation, reduce viability, or arrest cell growth. These data indicate that
      long-term culture expansion of mouse MSCs in atmospheric oxygen selects for
      clones with absent or impaired p53 function, which allows cells to escape oxygen
      induced growth inhibition. In contrast, expansion in 5% oxygen generates large
      numbers of primary mouse MSCs that retain sensitivity to atmospheric oxygen, and
      therefore a functional p53 protein, even after long-term expansion in vitro.

PMID- 22367741
TI  - Leukocyte counting from a small amount of whole blood using a size-controlled
      microcavity array.
AB  - Absolute counting of total leukocytes or specific subsets within small amounts of
      whole blood is difficult due to a lack of techniques that enable separation of
      all leukocytes from limited amounts of whole blood. In this study, a microfluidic
      device equipped with a size-controlled microcavity array for highly efficient
      separation of leukocytes from submicroliters of whole blood was developed. The
      microcavity array can separate leukocytes from whole blood based on differences
      in the size and deformability between leukocytes and other blood cells.
      Leukocytes recovered on aligned microcavities were continuously processed for
      image-based immunophenotypic analysis. Our device successfully recovered over 90%
      of leukocytes in 1 uL of whole blood without pretreatment such as density
      gradient centrifugation or erythrocyte lysis. In addition, the proposed system
      successfully performed absolute enumeration of human CD4(+) and CD8(+) leukocytes
      from 1 uL of whole blood, and the obtained data showed good correlation with
      conventional flow cytometric analysis. Our microfluidic device has great
      potential as a tool for a point-of-care leukocyte analysis system.

PMID- 22367740
TI  - Laparoscopic "single knot-single running" suture vesico-urethral anastomosis with
      posterior musculofascial reconstruction.
AB  - PURPOSE: To describe results of a simplified technique to configure the
      vesicourethral anastomosis and to restore posterior musculofascial plate during
      laparoscopic radical prostatectomy with a "single knot-single running" suture.
      METHODS: Between December 2006 and 2009, a conventional Van Velthoven anastomosis
      (group A) was applied in 125 cases while the novel anastomosis was applied in 155
      consecutive patients (group B). A between group comparison of continence recovery
      was performed with log-rank test and Chi-square test. Continuous variables were
      compared with Wilcoxon's test and categorical ones with Chi-square test. RESULTS:
      Median operative time and median time to configure the anastomosis were
      comparable between two groups. Proportions of patients using 0 pad, 1 pad and >1
      pad per day were statistically different between groups at 1 month (54.4%, 14.4%,
      31.2% vs. 52.3%, 27.7%, 20%, in group A and group B, respectively; p = 0.01), at
      3 months (73.6%, 8.8%, 17.6% vs. 86.5%, 7.1%, 6.5%; p = 0.01) and at 6 months
      (80.8%, 12.8%, 6.4% vs. 92.3%, 6.5%, 1.2%; p = 0.01). At log-rank test,
      continence recovery between two groups was statistically different (p = 0.008).
      CONCLUSIONS: The excellent outcome together with the easiness of performing this
      novel anastomosis compared to the traditional Van Velthoven make it widely
      reproducible.

PMID- 22367742
TI  - Stereochemical behavior of (77)Se-(1)H spin-spin coupling constants in pyrazolyl
      1,3-diselenanes and 1,2-diselenolane.
AB  - Conformational study of five derivatives of 2-(pyrazol-4-yl)-1,3-diselenane
      together with related 1,2-diselenolane in respect to the stereochemical trends of
      geminal and vicinal (77)Se-(1)H spin-spin coupling constants has been carried out
      by means of high-level theoretical calculations in combination with experiment.
      The marked dihedral angle dependences for both types of couplings accounted for
      the lone pair effect in the case of geminal coupling constants and the Karplus
      type relationship for vicinal couplings have been established, which is of major
      importance for the stereochemical analysis of saturated selenium containing
      heterocycles.

PMID- 22367739
TI  - Repression of miR-142 by p300 and MAPK is required for survival signalling via
      gp130 during adaptive hypertrophy.
AB  - An increase in cardiac workload, ultimately resulting in hypertrophy, generates
      oxidative stress and therefore requires the activation of both survival and
      growth signal pathways. Here, we wanted to characterize the regulators, targets
      and mechanistic roles of miR-142, a microRNA (miRNA) negatively regulated during
      hypertrophy. We show that both miRNA-142-3p and -5p are repressed by serum
      derived growth factors in cultured cardiac myocytes, in models of cardiac
      hypertrophy in vivo and in human cardiomyopathic hearts. Levels of miR-142 are
      inversely related to levels of acetyltransferase p300 and MAPK activity. When
      present, miR-142 inhibits both survival and growth pathways by directly targeting
      nodal regulators p300 and gp130. MiR-142 also potently represses multiple
      components of the NF-kappaB pathway, preventing cytokine-mediated NO production
      and blocks translation of alpha-actinin. Forced expression of miR-142 during
      hypertrophic growth induced extensive apoptosis and cardiac dysfunction;
      conversely, loss of miR-142 fully rescued cardiac function in a murine heart
      failure model. Downregulation of miR-142 is required to enable cytokine-mediated
      survival signalling during cardiac growth in response to haemodynamic stress and
      is a critical element of adaptive hypertrophy.

PMID- 22367743
TI  - Quantitative proteomics study on the protective mechanism of phlorizin on hepatic
      damage in diabetic db/db mice.
AB  - Although phlorizin has been used in the treatment of diabetes mellitus for over
      100 years, the underlying molecular mechanisms have not been fully elucidated.
      This study investigated the effect of phlorizin on body weight, blood glucose,
      blood triglycerides (TG), blood total cholesterol (TC), as well as overall
      changes in protein expression in db/db diabetic mouse liver. Phlorizin
      significantly decreased body weight gain and the levels of glucose, TC and TG in
      blood. Isobaric tag for relative and absolute quantitation (iTRAQ) quantitative
      proteomics profiling revealed that phlorizin interfered with the processes of
      carbohydrate metabolism, fatty acid biosynthesis and beta-oxidation, cholesterol
      biosynthesis, and free radical scavenging by affecting the expression of key
      proteins in these processes. Ingenuity Pathway Analysis successfully established
      several pathway networks, in which many differentially expressed proteins were
      involved. The differential expression of several proteins was validated by
      western blotting. Our study offers important information on the mechanism of
      phlorizin treatment in diabetes mellitus, particularly in the liver.

PMID- 22367744
TI  - Joint physical activity and sedentary behavior in parent-child pairs.
AB  - PURPOSE: The research examined joint physical activity and sedentary behavior
      among 291 parent-child pairs who both wore an accelerometer and Global
      Positioning System (GPS) device during the same 7-d period. METHODS: Children
      were 52.2% female, 8-14 yr, and 43.0% Hispanic. Parents were 87.6% female. An
      ActiGraph GT2M accelerometer and GlobalSat BT-335 GPS device collected activity
      and global positioning data, respectively. Linear distance between the parent and
      child for each 30-s epoch was calculated using geographic coordinates from the
      GPS. Joint behavior was defined as a separation distance less than 50 m between
      parents and children. RESULTS: On average, during nonschool waking hours, parents
      and children spent 2.4 +/- 4.1 min.d (mean +/- SD) performing moderate-to
      vigorous physical activity (MVPA) together and 92.9 +/- 40.1 min.d in sedentary
      behavior together. Children engaged in an average of 10 min.d of MVPA during
      nonschool waking hours when their parent was nearby but not engaging in MVPA.
      During this same period, parents engaged in 4.6 min.d of MVPA when their child
      was nearby but not engaging in MVPA. Household income level and the child's age
      were negatively associated with joint MVPA. Girls engaged in a greater percentage
      of their total MVPA together with their parent than boys. Girls and older
      children engaged in more sedentary behavior together with their parent than boys
      and younger children. Older parents engaged in a greater percentage of their
      sedentary behavior together with their children than younger parents.
      CONCLUSIONS: Replacing the time that parents and children spend together in
      sedentary pursuits with joint physical activity could have health benefits,
      especially for girls, older children, older parents, and higher income families.

PMID- 22367745
TI  - Metabolic cost of running barefoot versus shod: is lighter better?
AB  - PURPOSE: Based on mass alone, one might intuit that running barefoot would exact
      a lower metabolic cost than running in shoes. Numerous studies have shown that
      adding mass to shoes increases submaximal oxygen uptake (VO(2)) by approximately
      1% per 100 g per shoe. However, only two of the seven studies on the topic have
      found a statistically significant difference in VO(2) between barefoot and shod
      running. The lack of difference found in these studies suggests that factors
      other than shoe mass (e.g., barefoot running experience, foot strike pattern,
      shoe construction) may play important roles in determining the metabolic cost of
      barefoot versus shod running. Our goal was to quantify the metabolic effects of
      adding mass to the feet and compare oxygen uptake and metabolic power during
      barefoot versus shod running while controlling for barefoot running experience,
      foot strike pattern, and footwear. METHODS: Twelve males with substantial
      barefoot running experience ran at 3.35 m.s with a midfoot strike pattern on a
      motorized treadmill, both barefoot and in lightweight cushioned shoes (~150 g per
      shoe). In additional trials, we attached small lead strips to each foot/shoe
      (~150, ~300, and ~450 g). For each condition, we measured the subjects' rates of
      oxygen consumption and carbon dioxide production and calculated metabolic power.
      RESULTS: VO(2) increased by approximately 1% for each 100 g added per foot,
      whether barefoot or shod (P < 0.001). However, barefoot and shod running did not
      significantly differ in VO(2) or metabolic power. A consequence of these two
      findings was that for footwear conditions of equal mass, shod running had ~3%-4%
      lower VO(2) and metabolic power demand than barefoot running (P < 0.05).
      CONCLUSIONS: Running barefoot offers no metabolic advantage over running in
      lightweight, cushioned shoes.

PMID- 22367746
TI  - Structural glycobiology of the major allergen of Artemisia vulgaris pollen, Art v
      1: O-glycosylation influence on the protein dynamics and allergenicity.
AB  - Art v 1 is the major allergen of mugwort (Artemisia vulgaris) pollen. It is
      formed by an N-terminal globular defensin-like part and a C-terminal proline-rich
      domain. As the structure and the dynamics of Art v 1 have been mostly described
      for its recombinant, non-glycosylated form, which does not occur in normal plant
      physiology, the present work intends to obtain a three-dimensional model for Art
      v 1 native O-glycosylation structure and to evaluate the influence of such
      glycans over the protein dynamics and allergenicity through molecular dynamics
      simulations in triplicates. Structural insights into the mutual recognition of
      Art v 1 protein and carbohydrate moieties recognition by antibodies were
      obtained, in which glycan chains remained close to the previously identified
      epitopes in the defensin-like domain, thus pointing to potential interferences
      with antibodies recognition. To our knowledge, this is the first structural
      report of an entire furanose-containing glycoprotein. As well, together with the
      previously determined NMR structures, the obtained results contribute in the
      comprehension of the effect of glycosylation over both proline-rich and defensin
      like domains, providing an atomic representation of such alterations.

PMID- 22367747
TI  - Sebaceous gland carcinoma of the head and neck: the Princess Margaret Hospital
      experience.
AB  - BACKGROUND: The purpose of this study was to identify prognostic factors
      predicting outcomes in sebaceous gland carcinomas. METHODS: We conducted a
      retrospective medical chart review of patients with sebaceous carcinomas of
      periorbital (n = 33) and extraorbital sites (n = 13). RESULTS: Patients with
      periorbital tumors had higher recurrence rates than did patients with
      extraorbital tumors (64% vs 23%; p = .032). Patients who were older than 60 years
      (p = .035) and had lower eyelid tumors (p < .0001) had a lower disease-free
      survival rate than did patients with upper eyelid tumors. Patients with sebaceous
      carcinomas had a high rate (60%) of occult lymph node metastases. CONCLUSION:
      Periorbital tumors are associated with poorer outcomes than are extraorbital
      tumors. Lower eyelid carcinomas have the worst prognosis and should be treated
      more aggressively. Our findings of a high incidence of occult neck disease and a
      high rate of regional recurrence in patients with sebaceous carcinomas support
      the consideration of prophylactic elective neck dissections for treating such
      patients.

PMID- 22367748
TI  - Bayesian phylogenetics with BEAUti and the BEAST 1.7.
AB  - Computational evolutionary biology, statistical phylogenetics and coalescent
      based population genetics are becoming increasingly central to the analysis and
      understanding of molecular sequence data. We present the Bayesian Evolutionary
      Analysis by Sampling Trees (BEAST) software package version 1.7, which implements
      a family of Markov chain Monte Carlo (MCMC) algorithms for Bayesian phylogenetic
      inference, divergence time dating, coalescent analysis, phylogeography and
      related molecular evolutionary analyses. This package includes an enhanced
      graphical user interface program called Bayesian Evolutionary Analysis Utility
      (BEAUti) that enables access to advanced models for molecular sequence and
      phenotypic trait evolution that were previously available to developers only. The
      package also provides new tools for visualizing and summarizing multispecies
      coalescent and phylogeographic analyses. BEAUti and BEAST 1.7 are open source
      under the GNU lesser general public license and available at http://beast
      mcmc.googlecode.com and http://beast.bio.ed.ac.uk.

PMID- 22367749
TI  - Impact of soil water chemistry on the apparent sex ratio of the flowering ramets
      of the dioecious plant Myrica gale var. tomentosa.
AB  - We determined whether the apparent (M/Fl) sex ratio (male ramets/flowering
      ramets) and apparent reproductive ramet ratio (Fl/Li ratio; flowering
      ramets/living ramets) in 15 Myrica gale var. tomentosa populations varied with
      dissolved total nitrogen, dissolved total phosphorus, potassium, magnesium,
      calcium, or pH in the soil water. Our aim was to define the environmental factors
      affecting the M/Fl sex ratio and Fl/Li ratio of the populations. We also examined
      the habitat conditions of these populations by analyzing soil water chemistry and
      water dynamics. In 2007, 3 of the 15 populations had no females. The remaining 12
      had significantly male-biased (M/Fl sex ratio = 0.59-0.97). Although we could not
      explain the absence of females by the current potassium levels alone, as
      potassium increased, so did the M/Fl sex ratio. As nitrogen increased and
      potassium decreased, Fl/Li ratio decreased. Our soil water chemistry analyses
      suggested that the potassium supply by soil surface erosion from flooding and the
      inflow of anthropogenic nitrogen were the important factors influencing the M/Fl
      sex ratio and Fl/Li ratio. Nitrogen management would be important in one of the
      endangered populations where inflow of nitrogen was the highest among 15
      habitats.

PMID- 22367750
TI  - Arterial reservoir-excess pressure and ventricular work.
AB  - This study is based on the hypothesis that the pressure within the arterial
      network can be usefully decomposed as the sum of a reservoir pressure and an
      excess pressure. The reservoir pressure waveform is defined to be the same in
      each vessel but delayed by the wave travel time from the root of the aorta. Using
      calculus of variations and mass conservation, which relates the flow and rates of
      change of pressure in the vessels, we show that the reservoir pressure waveform
      minimises the ventricular hydraulic work for any physiologically or clinically
      reasonable ejection waveform and arterial properties, i.e. vessel compliances and
      terminal resistances. We conclude that the excess pressure determines the excess
      work done by the ventricle, which may have clinically important implications.

PMID- 22367751
TI  - Initial experience from a double-blind, placebo-controlled, clinical outcome
      study of ARC1779 in patients with thrombotic thrombocytopenic purpura.

PMID- 22367752
TI  - AIDS-related stigma, HIV testing, and transmission risk among patrons of informal
      drinking places in Cape Town, South Africa.
AB  - BACKGROUND: AIDS-related stigma as a barrier to HIV testing has not been examined
      within the context of high at risk environments such as drinking venues. Of
      particular importance is whether AIDS-related stigma is associated with HIV
      transmission risks among people who have never been tested for HIV. PURPOSE: We
      examined: (1) AIDS-related stigma as a barrier to testing, controlling for other
      potential barriers, and (2) whether stigma is associated with HIV risks among HIV
      untested individuals. METHODS: We surveyed 2,572 individuals attending informal
      drinking establishments in Cape Town, South Africa to assess HIV testing status,
      AIDS-related stigma endorsement, and HIV transmission sexual risk behavior.
      RESULTS: Endorsement of AIDS-related stigma was negatively associated with HIV
      lifetime testing. In addition, stigma endorsement was associated with higher HIV
      transmission risks. CONCLUSION: AIDS-related stigma must be addressed in HIV
      prevention campaigns across South Africa. Antistigma messages should be
      integrated with risk reduction counseling and testing.

PMID- 22367753
TI  - Commentary on Manne et al.: Using the interdependence model to understand spousal
      influence on colorectal cancer screening intentions: a structural equation model.

PMID- 22367754
TI  - Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in
      human macrophages.
AB  - Macrophages respond to cholesterol accumulation by increasing cholesterol efflux,
      which is mediated by activation of the nuclear liver X receptor (LXR) and ATP
      binding cassette (ABC) transporters. In the present study, we investigated
      whether foam cell formation induced by phospholipase A(2)-modified low-density
      lipoprotein (PLA-LDL) influences LXR activity and cholesterol efflux in primary
      human monocyte-derived macrophages (MDMs). Macrophages were treated with PLA-LDL
      and expression of the LXR target genes ABCA1 and ABCG1 was analyzed by
      quantitative PCR and western blot. PLA-LDL time-dependently up-regulated ABCA1
      and ABCG1 mRNA and protein. Removal of non-esterified fatty acids from PLA-LDL
      particles did not influence the induction of ABC transporters. A role of LXR in
      PLA-LDL-stimulated ABCG1 expression was verified by LXR-knockdown and luciferase
      reporter assays using a construct containing a LXR response element from the
      ABCG1 gene. Functionally, cholesterol efflux to apolipoprotein A-I and high
      density lipoprotein was higher in PLA-LDL treated cells compared to controls.
      Together, these results demonstrate that in primary human MDMs PLA-LDL induces
      ABC transporter expression via LXR activation. A concomitantly increased
      cholesterol efflux may prevent excessive cholesterol accumulation and thus,
      attenuate foam cell formation.

PMID- 22367755
TI  - Do pigeons prefer information in the absence of differential reinforcement?
AB  - Prior research has indicated that pigeons do not prefer an alternative that
      provides a sample (for matching to sample) over an alternative that does not
      provide a sample (i.e., there is no indication of which comparison stimulus is
      correct). However, Zentall and Stagner (Journal of Experimental Psychology.
      Animal Behavior Processes 36:506-509, 2010) showed that when delay of
      reinforcement was controlled, pigeons had a strong preference for matching over
      pseudomatching (i.e., there was a sample, but it did not indicate which
      comparison stimulus was correct). Experiment 1 of the present study replicated
      and extended the results of the Zentall and Stagner (Journal of Experimental
      Psychology. Animal Behavior Processes 36:506-509, 2010) study by including an
      identity relation between the sample and one of the comparison stimuli in both
      the matching and pseudomatching tasks. In Experiment 2, in which we asked whether
      the pigeons would still prefer matching if we equated the two tasks for
      probability of reinforcement, we found no systematic preference for matching over
      pseudomatching. Thus, it appears that in the absence of differential
      reinforcement, the information provided by a sample that signals which of the two
      comparison stimuli is correct is insufficient to produce a preference for that
      alternative.

PMID- 22367756
TI  - Synthesis, computational modeling, and properties of benzo-appended BODIPYs.
AB  - A series of new functionalized mono- and dibenzo-appended BODIPY dyes were
      synthesized from a common tetrahydroisoindole precursor following two different
      synthetic routes. Route A involved the assembly of the BODIPY core prior to
      aromatization, while in Route B the aromatization step was performed first. In
      general, Route A gave higher yields of the target dibenzo-BODIPYs, due to the
      ease of aromatization of the BODIPYs compared with the corresponding
      dipyrromethenes, probably due to their higher stability under the oxidative
      conditions (2,3-dichloro-5,6-dicyano-1,4-benzoquinone in refluxing toluene).
      However, due to the slow oxidation of highly electron-deficient BODIPY 3 c
      bearing a meso-C(6)F(5) group, dibenzo-BODIPY 4 c was obtained, in 35 % overall
      from dipyrromethane, only by Route B. Computational calculations performed at the
      6-31G(d,p) level are in agreement with the experimental results, showing similar
      relative energies for all reaction intermediates in both routes. In addition,
      BODIPY 3 c had the highest molecular electrostatic potential (MEPN), confirming
      its high electron deficiency and consequent resistance toward oxidation. X-ray
      analyses of eight BODIPYs and several intermediates show that benzannulation
      further enhances the planarity of these systems. The pi-extended BODIPYs show
      strong red-shifted absorptions and emissions, about 50-60 nm per benzoannulated
      ring, at 589-658 and 596-680 nm, respectively. In particular, db-BODIPY 4 c
      bearing a meso-C(6)F(5) group showed the longest lambda(max) of absorption and
      emission, along with the lowest fluorescence quantum yield (0.31 in CH(2)Cl(2));
      on the other hand monobenzo-BODIPY 8 showed the highest quantum yield (0.99) of
      this series. Cellular investigations using human carcinoma HEp2 cells revealed
      high plasma membrane permeability for all dibenzo-BODIPYs, low dark- and photo
      cytotoxicities and intracellular localization in the cell endoplasmic reticulum,
      in addition to other organelles. Our studies indicate that benzo-appended
      BODIPYs, in particular the highly stable meso-substituted BODIPYs, are promising
      fluorophores for bioimaging applications.

PMID- 22367758
TI  - Group 3 metal initiators with an [OSSO]-type bis(phenolate) ligand for the
      stereoselective polymerization of lactide monomers.
AB  - A series of 1,omega-dithiaalkanediyl-bridged bis(phenols) of the general type
      [OSSO]H(2) with variable steric properties and various bridges were prepared. The
      stoichiometric reaction of the bis(phenols) 1,3-dithiapropanediyl-2,2'-bis(4,6-di
      tert-butylphenol), 1,3-dithiapropanediyl-2,2'-bis[4,6-di(2-phenyl-2
      propyl)phenol], rac-2,3-trans-propanediyl-1,4-dithiabutanediyl-2,2'-bis[4,6-di(2
      phenyl-2-propyl)phenol], rac-2,3-trans-butanediyl-1,4-dithiabutane diyl-2,2'
      bis[4,6-di(2-phenyl-2-propyl)phenol], rac-2,3-trans-hexanediyl-1,4
      dithiabutanediyl-2,2'-bis[4,6-di(2-phenyl-2-propyl)phenol], 1,3-dithiapropanediyl
      2,2'-bis[6-(1-methylcyclohexyl)-4-methylphenol] (C(1), R=1-methylcyclohexyl), and
      1,4-dithiabutanediyl-2,2'-bis[6-(1-methylcyclohexyl)-4-methylphenol] with rare
      earth metal silylamido precursors [Ln{N(SiHMe(2))(2)(3)(thf)(x)] (Ln=Sc, x=1 or
      Ln=Y, x=2; thf=tetrahydrofuran) afforded the corresponding scandium and yttrium
      bis(phenolate) silylamido complexes [Ln(OSSO){N(SiHMe(2))(2)}(thf)] in moderate
      to good yields. The monomeric nature of these complexes was shown by an X-ray
      diffraction study of one of the yttrium complexes. The complexes efficiently
      initiated the ring-opening polymerization of rac- and meso-lactide to give
      heterotactic-biased poly(rac-lactides) and highly syndiotactic poly(meso
      lactides). Variation of the ligand backbone and the steric properties of the
      ortho substituents affected the level of tacticity in the polylactides.

PMID- 22367760
TI  - Influences of encoding and retrieval on the steady-state visual evoked potential.
AB  - The steady-state visual evoked potential (SSVEP) is a powerful tool to study
      basic perceptual functions in the human electroencephalogram (EEG) (e.g.
      selective attention). The present study aimed at finding support for the SSVEP's
      sensitivity to higher cognitive functions (e.g. memory). We tagged pictures of
      meaningless objects with 15 Hz within a combined subsequent-memory and
      recognition-memory design. The EEG was recorded from 128 electrodes. The
      subsequent-memory design revealed that SSVEPs are influenced by encoding-related
      processes. In particular, successful encoding was associated with higher SSVEP
      amplitudes at central-parietal scalp electrodes and reduced activity at left
      occipital sites. Recognition memory led to higher SSVEP amplitudes at right
      temporal scalp regions and to an amplitude reduction at midline electrodes. For
      the first time it was demonstrated that the SSVEP technique is a useful tool to
      study memory encoding and retrieval. SSVEPs might reflect the ongoing dynamics
      within an externally driven and widespread task-relevant network. This offers
      remarkable possibilities for future research on electrophysiological correlates
      of mnemonic functioning.

PMID- 22367759
TI  - Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit
      extraembryonic differentiation.
AB  - Embryonic stem cell (ESC) identity and self-renewal is maintained by extrinsic
      signaling pathways and intrinsic gene regulatory networks. Here, we show that
      three members of the Ccr4-Not complex, Cnot1, Cnot2, and Cnot3, play critical
      roles in maintaining mouse and human ESC identity as a protein complex and
      inhibit differentiation into the extraembryonic lineages. Enriched in the inner
      cell mass of blastocysts, these Cnot genes are highly expressed in ESC and
      downregulated during differentiation. In mouse ESCs, Cnot1, Cnot2, and Cnot3 are
      important for maintenance in both normal conditions and the 2i/LIF medium that
      supports the ground state pluripotency. Genetic analysis indicated that they do
      not act through known self-renewal pathways or core transcription factors.
      Instead, they repress the expression of early trophectoderm (TE) transcription
      factors such as Cdx2. Importantly, these Cnot genes are also necessary for the
      maintenance of human ESCs, and silencing them mainly lead to TE and primitive
      endoderm differentiation. Together, our results indicate that Cnot1, Cnot2, and
      Cnot3 represent a novel component of the core self-renewal and pluripotency
      circuitry conserved in mouse and human ESCs.

PMID- 22367761
TI  - Patterns of root respiration rates and morphological traits in 13 tree species in
      a tropical forest.
AB  - The root systems of forest trees are composed of different diameters and
      heterogeneous physiological traits. However, the pattern of root respiration
      rates from finer and coarser roots across various tropical species remains
      unknown. To clarify how respiration is related to the morphological traits of
      roots, we evaluated specific root respiration and its relationships to mean root
      diameter (D) of various diameter and root tissue density (RTD; root mass per unit
      root volume; gcm(-3)) and specific root length (SRL; root length per unit root
      mass; mg(-1)) of the fine roots among and within 14 trees of 13 species from a
      primary tropical rainforest in the Pasoh Forest Reserve in Peninsular Malaysia.
      Coarse root (2-269mm) respiration rates increased with decreasing D, resulting in
      significant relationships between root respiration and diameter across species. A
      model based on a radial gradient of respiration rates of coarse roots simulated
      the exponential decrease in respiration with diameter. The respiration rate of
      fine roots (<2mm) was much higher and more variable than those of larger diameter
      roots. For fine roots, the mean respiration rates for each species increased with
      decreasing D. The respiration rates of fine roots declined markedly with
      increasing RTD and increased with increasing SRL, which explained a significant
      portion of the variation in the respiration among the 14 trees from 13 species
      examined. Our results indicate that coarse root respiration in tree species
      follows a basic relationship with D across species and that most of the variation
      in fine root respiration among species is explained by D, RTD and SRL. We found
      that the relationship between root respiration and morphological traits provides
      a quantitative basis for separating fine roots from coarse roots and that the
      pattern holds across different species.

PMID- 22367762
TI  - Effect of flooding on C metabolism of flood-tolerant (Quercus robur) and non
      tolerant (Fagus sylvatica) tree species.
AB  - Flooding is assumed to cause an energy crisis in plants because-due to a lack of
      O(2)-mitochondrial respiration is replaced by alcoholic fermentation which yields
      considerably less energy equivalents. In the present study, the effect of
      flooding on the carbon metabolism of flooding-tolerant pedunculate oak (Quercus
      robur L.) and flooding-sensitive European beech (Fagus sylvatica L.) seedlings
      was characterized. Whereas soluble carbohydrate concentrations dropped in roots
      of F. sylvatica, they were constant in Q. robur during flooding. At the same
      time, root alcohol dehydrogenase activities were decreased in beech but not in
      oak, suggesting substrate limitation of alcoholic fermentation in beech roots.
      Surprisingly, leaf and phloem sap sugar concentrations increased in both species
      but to a much higher degree in beech. This finding suggests that the phloem
      unloading process in flooding-sensitive beech was strongly impaired. It is
      assumed that root-derived ethanol is transported to the leaves via the
      transpiration stream. This mechanism is considered an adaptation to flooding
      because it helps avoid the accumulation of toxic ethanol in the roots and
      supports the whole plant's carbon metabolism by channelling ethanol into the
      oxidative metabolism of the leaves. A labelling experiment demonstrated that in
      the leaves of flooded trees, ethanol metabolism does not differ between flooded
      beech and oak, indicating that processes in the roots are crucial for the trees'
      flooding tolerance.

PMID- 22367763
TI  - Edge type affects leaf-level water relations and estimated transpiration of
      Eucalyptus arenacea.
AB  - While edge effects on tree water relations are well described for closed forests,
      they remain under-examined in more open forest types. Similarly, there has been
      minimal evaluation of the effects of contrasting land uses on the water relations
      of open forest types in highly fragmented landscapes. We examined edge effects on
      the water relations and gas exchange of a dominant tree (Eucalyptus arenacea
      Marginson & Ladiges) in an open forest type (temperate woodland) of south-eastern
      Australia. Edge effects in replicate woodlands adjoined by cleared agricultural
      land (pasture edges) were compared with those adjoined by 7- to 9-year-old
      eucalypt plantation with a 25m fire break (plantation edges). Consistent with
      studies in closed forest types, edge effects were pronounced at pasture edges
      where photosynthesis, transpiration and stomatal conductance were greater for
      edge trees than interior trees (75m into woodlands), and were related to greater
      light availability and significantly higher branch water potentials at woodland
      edges than interiors. Nonetheless, gas exchange values were only ~50% greater for
      edge than interior trees, compared with ~200% previously found in closed forest
      types. In contrast to woodlands adjoined by pasture, gas exchange in winter was
      significantly lower for edge than interior trees in woodlands adjoined by
      plantations, consistent with shading and buffering effects of plantations on edge
      microclimate. Plantation edge effects were less pronounced in summer, although
      higher water use efficiency of edge than interior woodland trees indicated
      possible competition for water between plantation trees and woodland edge trees
      in the drier months (an effect that might have been more pronounced were there no
      firebreak between the two land uses). Scaling up of leaf-level water relations to
      stand transpiration using a Jarvis-type phenomenological model indicated similar
      differences between edge types. That is, transpiration was greater at pasture
      than plantation edges in summer months (most likely due to greater water
      availability at pasture edges), resulting in significantly greater estimates of
      annual transpiration at pasture than plantation edges (430 vs. 343lm(-2)year(-1),
      respectively). Our study highlights the need for landscape-level water flux
      models to account for edge effects on stand transpiration, particularly in highly
      fragmented landscapes.

PMID- 22367764
TI  - Supracricoid partial laryngectomy with cricothyroidopexy: a treatment for
      anterior vocal commissure laryngeal squamous carcinoma.
AB  - BACKGROUND: The clinical efficiency and functional outcomes of supracricoid
      partial laryngectomy (SCPL) with cricothyroidopexy (CTP) were compared with those
      of the traditional SCPL with cricohyoidoepiglottopexy (CHEP) in treating
      laryngeal squamous carcinoma involving anterior vocal commissure (AVC). METHODS:
      From January 2000 to June 2009, 50 patients diagnosed with early- or intermediate
      stage (T1b-T3 classification) glottic cancer involving AVC were treated with SCPL
      CHEP or SCPL-CTP. Postoperative complications, local recurrence, survival rate,
      and speech performance were compared between these 2 surgical procedures.
      RESULTS: Patients undergoing SCPL-CHEP or SCPL-CTP manifested similar levels of
      postoperative complications, tumor recurrence, and survival rates. However, the
      SCPL-CTP group showed significantly lower Voice Handicap Index (VHI) scores,
      higher maximum phonation time, and improved glottic reconstruction and closure
      than the SCPL-CHEP group. CONCLUSION: The SCPL-CTP procedure better preserves
      postoperative speech performance than the SCPL-CHEP procedure, underscoring the
      moderate effectiveness of SCPL-CTP as a treatment for laryngeal squamous
      carcinoma involving AVC.

PMID- 22367765
TI  - Using improvement science to promote evidence-based practice in a childhood
      cancer and hematology center.
AB  - A major children's cancer and hematology center established a Quality
      Transformation (QT) Core to develop and monitor empirical outcomes that
      demonstrate excellence in clinical care. The QT Core, based on the Institute of
      Medicine's domains of quality health care, aims to ensure that care is safe,
      effective, patient centered, timely, efficient, and equitable. Specific goals for
      the first year of the QT Core were to develop a team of improvement science
      experts, engage faculty and staff in QT initiatives, promote accountability for
      excellence in clinical care, and establish specific metrics to evaluate process,
      structure, and outcomes for QT Core projects. The purpose of this article is to
      discuss the successful development of a quality transformation core within a
      pediatric subspecialty and demonstrate the principles of improvement science
      through an actual quality transformation project designed to implement an
      evidence-based guideline for procedural sedation for children with cancer. The QT
      Core within this subspecialty was founded on principles of successful
      transformation of patient care that includes motivation to change, leaders
      committed to quality, active engagement of staff in meaningful problem-solving
      initiatives, alignment with organization goals with resource allocation, and
      integration to bridge boundaries throughout an organization. These key principles
      are demonstrated through the discussion of the development of the QT Core and
      implementation of an evidence-based procedure sedation guideline. Pediatric and
      pediatric subspecialty groups can be on the forefront of national initiatives
      that promote quality health care, exemplified by the QT Core developed within the
      cancer and hematology center.

PMID- 22367766
TI  - "Targeting to zero" in pediatric oncology: a review of central venous catheter
      related bloodstream infections.
AB  - Reducing or eliminating hospital acquired infections is a national quality of
      care priority. The majority of the 12,400 children diagnosed with cancer each
      year require long-term intravenous access to receive intensive and complex
      therapies. These children are at high risk for infection by nature of their
      disease and treatment, which often involves use of a central venous catheter
      (CVC). Throughout the nation, nurses assume frontline responsibility for safe,
      quality CVC care to minimize the risk of potentially life-threatening infections.
      Substantial financial and human costs are associated with CVC-related bloodstream
      infections, including prolonged hospital lengths of stay and increased care
      required to treat these infections. The purpose of this review of the literature
      is to summarize existing adult and pediatric data on CVC-related bloodstream
      infections and explore nursing models of CVC care that may improve pediatric
      oncology patient outcomes.

PMID- 22367767
TI  - Pain experience in children with advanced cancer.
AB  - BACKGROUND: It is important for health care professionals to understand the pain
      experience in children with advanced cancer. There has been increased attention
      to this topic, but systematic studies are limited. OBJECTIVE: To examine pain
      symptoms and management in children with advanced cancer using child self-report
      and nurse documentation. METHODS: A prospective, longitudinal method was used to
      collect data from 62 children over a 5-month period. Children were English and
      Spanish speaking, ages 6 to 17 years, with advanced cancer. Nurses also provided
      data. RESULTS: Across all interviews, pain was reported 56% of the time by all
      children. Nurses documented pain only 23% of the time. Children most frequently
      reported head pain (31%), followed by abdomen, lower back, leg, and feet pain
      (20% to 30%). Children consistently reported more intense pain compared with
      nurses. Nonopioids were used more frequently (45%) than opioids (32%), and
      nurses' perception of pain intensity was more highly correlated with
      administration of opioids (r = .72, P < .001). Children who died during their
      participation in this study received more opioids over time. Pain intensity was
      relatively stable over time. Nurses noted ethnicity related differences with
      higher pain levels for Caucasian children, who received analgesics more
      frequently. DISCUSSION: The children consistently reported pain. Child self
      report and nurse documentation of pain differed, as did pain management among
      children who died compared with those who did not. Ethnicity differences in the
      identification and management of pain by nurses begs further study. Overall,
      nurses were aware of and responsive to pain and pain management.

PMID- 22367768
TI  - Osteogenesis imperfecta and bone marrow transplant.
AB  - The first attempted bone marrow transplant (BMT) dates back to 1896. In the
      following centuries, the medical community pioneered an ongoing progression of
      breakthroughs. In 1954 the first successful solid organ transplant, the kidney,
      was performed. In the 1960s advances led to the first successful lung, pancreas,
      liver and heart transplant and in 1973 the first successful BMT was achieved. BMT
      has traditionally been used to treat malignant diseases. However, scientific and
      technological progress has expanded its scope and today, BMT is used to treat a
      spectrum of diseases. While BMT is a complex procedure, the medical community
      expects that it will one day play a role in the treatment of other diseases. As
      the science evolves, it is essential that nurses educate themselves about these
      emerging transplant populations, one of which is children with osteogenesis
      impefecta. This manuscript will provide nurses with a critical background on the
      disease, a description of the transplant theory, and the implications for the
      nursing care of these children.

PMID- 22367769
TI  - School liaison program for children with brain tumors.
AB  - A school liaison program that familiarized teachers with the implications of each
      child's brain tumor treatment with respect to learning, behavior, and
      socialization was implemented. The study explored the experiences of nine
      families and their teachers and health staff who participated in the program. The
      successes and challenges of the program were captured through interviews that
      were audio-taped and transcribed verbatim for data analysis. Individualized
      programs were negotiated between families and education staff to address
      behavioral, academic, and social needs of each child. Children were able to learn
      to their ability rather than be judged on the achievements of their respective
      grade levels. Parents reported that the program strengthened their advocacy
      skills and improved the children's social and learning achievements. Teachers
      reported an improved ability to provide more comprehensive educational
      programming suited to the child's needs. Overall, most children in the program
      achieved or exceeded their initial academic, social, and behavioral expectations.
      The school liaison program demonstrated significant potential to enhance the
      learning experience for children with brain tumors.

PMID- 22367770
TI  - Allocating scarce financial resources for HIV treatment: benchmarking prices of
      antiretroviral medicines in Latin America.
AB  - Public sector price analyses of antiretroviral (ARV) medicines can provide
      relevant information to detect ARV procurement procedures that do not obtain
      competitive market prices. Price benchmarks provide a useful tool for programme
      managers and policy makers to support such planning and policy measures. The aim
      of the study was to develop regional and global price benchmarks which can be
      used to analyse public-sector price variability of ARVs in low- and middle-income
      countries using the procurement prices of Latin America and the Caribbean (LAC)
      countries in 2008 as an example.  We used the Global Price Reporting Mechanism
      (GPRM) data base, provided by the World Health Organization (WHO), for 13 LAC
      countries' ARV procurements to analyse the procurement prices of four first-line
      and three second-line ARV combinations in 2008. First, a cross-sectional analysis
      was conducted to compare ARV combination prices. Second, four different price
      'benchmarks' were created and we estimated the additional number of patients who
      could have been treated in each country if the ARV combinations studied were
      purchased at the various reference ('benchmark') prices.  Large price variations
      exist for first- and second-line ARV combinations between countries in the LAC
      region. Most countries in the LAC region could be treating between 1.17 and 3.8
      times more patients if procurement prices were closer to the lowest regional
      generic price. For all second-line combinations, a price closer to the lowest
      regional innovator prices or to the global median transaction price for lower
      middle-income countries would also result in treating up to nearly five times
      more patients.  Some rational allocation of financial resources due, in part, to
      price benchmarking and careful planning by policy makers and programme managers
      can assist a country in negotiating lower ARV procurement prices and should form
      part of a sustainable procurement policy.

PMID- 22367771
TI  - C6-substituted purine derivatives: an experimental and theoretical 1H, 13C and
      15N NMR study.
AB  - We measured the (1)H, (13)C and (15)N chemical shifts for a series of purine
      derivatives bearing a norbornane substituent in position 9 and various
      substituents in position 6. The experimental data were complemented with density
      functional theory (DFT) calculations. The comparison of the calculated and
      experimental chemical shifts provided us with information about the tautomer and
      conformational equilibria of the studied compounds.

PMID- 22367772
TI  - Autologous stem cell transplant is feasible in very elderly patients with
      lymphoma and limited comorbidity.

PMID- 22367773
TI  - Ten-year follow-up of skin-sparing mastectomy followed by immediate breast
      reconstruction.
AB  - BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by
      immediate breast reconstruction (IBR) is debated owing to a presumed compromise
      in the completeness of mastectomy. Current evidence is poor as it is based mostly
      on short-term follow-up data from highly selected patients. METHODS: A
      prospectively maintained institutional database was searched to identify patients
      who underwent SSM and IBR between 1995 and 2000. A retrospective review of
      medical records was carried out, including only patients with ductal carcinoma in
      situ and invasive breast cancer. During this time all patients treated with
      mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data
      from 253 consecutive patients with IBR were reviewed. Patients with incomplete
      follow-up data and those undergoing SSM for recurrent disease following previous
      lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women
      requiring mastectomy resulted in a large proportion of patients with advanced
      disease. During a median follow-up of 119 months, 17 (8.2 per cent) locoregional,
      six (2.9 per cent) local and 22 (10.6 per cent) distant recurrences were
      detected; the overall recurrence rate was 39 (18.8 per cent). Overall recurrence
      rate was associated with axillary lymph node metastasis (P = 0.009), higher stage
      (P < 0.001) and higher tumour grade (P = 0.031). The breast cancer-specific
      survival rate was 90.8 per cent (19 of 207 women died from recurrence).
      CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an
      oncologically safe treatment option regardless of tumour stage.

PMID- 22367774
TI  - Where is the most common site of DVT? Evaluation by CT venography.
AB  - PURPOSE: Our aim was to clarify the common site of deep venous thrombosis (DVT)
      in patients suspected of having pulmonary embolism using computed tomography
      pulmonary angiography with computed tomography venography (CTV). MATERIALS AND
      METHODS: We evaluated 215 patients. For all studies, 100 ml of 370 mg I/ml
      nonionic contrast material was administered. CTV were scanned with helical
      acquisition starting at 3 min in four-slice multidetector-row computed tomography
      (MDCT) or 5 min in 64-MDCT after the start of contrast material injection. The
      site of DVT was divided into iliac vein, femoral vein, popliteal vein, or calf
      vein. Calf vein was divided into muscular (soleal and gastrocnemius) and
      nonmuscular (anterior/posterior tibial and peroneal) veins. The 2 * 2 chi-square
      test was used. RESULTS: One hundred and thirty-seven patients showed DVT; the
      muscular calf vein was more prevalent than other veins (P < 0.01). CONCLUSIONS:
      Our study showed that the most common site of DVT was the muscular calf vein.

PMID- 22367775
TI  - Radiological findings as favorable predictors of pain relief in patients with
      osteoporotic compression fractures after percutaneous vertebroplasty: a
      retrospective study of 156 cases.
AB  - PURPOSE: We evaluated the relationships between pre-procedural radiological
      findings and short-term pain relief in patients with osteoporotic compression
      fractures after percutaneous vertebroplasty (PVP). MATERIALS AND METHODS: A
      retrospective review of pre-procedural radiological images of 156 patients with
      painful osteoporotic compression fracture was performed. Pain was measured with a
      visual analogue scale (VAS). Complete pain relief was defined as a VAS pain score
      of 0 or 1 at 3 months after PVP. Statistical analyses were conducted to evaluate
      the relationship between the pre-procedural imaging factors and pain relief using
      Pearson's chi-squared test. Multivariate logistic regression analysis was also
      performed. RESULTS: Complete pain relief was obtained in 45.5% of patients. An
      intravertebral cleft larger than half the height of the fractured vertebral body
      (FVB) was a significant key factor in the complete pain relief group after 3
      months. Further, >=40% of the spinal canal occupied by bony fragments of the FVB
      was related to incomplete pain relief. CONCLUSION: A large intravertebral cleft
      was a favorable short-term outcome predictor in patients with osteoporotic
      compression fractures after PVP, while severe protrusion of the FVB causing
      lumbar spinal canal stenosis was not a favorable short-term outcome predictor of
      complete pain relief.

PMID- 22367776
TI  - Use of n-butyl cyanoacrylate in abdominal and pelvic embolotherapy: indications
      and techniques, complications, and their management.
AB  - The purpose of this article is to describe the indications for use of n-butyl
      cyanoacrylate (NBCA) in abdominal and pelvic embolotherapy, appropriate
      techniques for NBCA embolotherapy, and NBCA-related complications and their
      management. NBCA embolotherapy is a feasible and effective method for treating a
      variety of abdominal and pelvic vascular lesions or tumors; however, the
      techniques suitable for each case and knowledge of NBCA-related complications are
      essential to achieve favorable outcomes.

PMID- 22367778
TI  - Catonella morbi as a cause of native valve endocarditis in Chennai, India.

PMID- 22367777
TI  - Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern
      Italy.
AB  - OBJECTIVES: The introduction of vaccination against hepatitis B initially reduced
      the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections,
      but the decreasing trend of HDV infection seems to have stopped. The aim of this
      study was to assess the prevalence of HDV infection in the general population
      living in the catchment area of Legnano Hospital in northern Italy. METHODS: Of
      the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B
      surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were
      subsequently tested for anti-HDV antibodies. RESULTS: Of the 488 subjects who
      tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30
      and 60 years. The difference in prevalence between males (7.1%) and females
      (1.9%) was statistically significant (p < 0.05), but not that between Italian
      (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV
      seropositivity between the patients with acute (0%) and chronic infections
      (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not
      statistically significant, but there was a significant difference (p < 0.01)
      between those with asymptomatic (2.1%) and clinically symptomatic infections
      (10.3%). Intravenous drug abuse was the main source of infection. CONCLUSIONS: In
      the catchment area of our hospital, the prevalence of HDV infection does not seem
      to be due to patients of non-Italian origin, but to Italian patients who are not
      vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s.
      Nevertheless, the increase in the number of immigrants from non-EU countries in
      recent years is soon likely to lead to a change in the epidemiology of HDV.

PMID- 22367779
TI  - Cancer screening of the uterine cervix papanicolaou smears versus state-of-the
      art human papillomavirus testing.
AB  - The article by Albrow et al in this issue describes the early cervical screening
      program in England as being "disorganized," but goes on to describe significant
      improvements over 20 years. It has become one of the leading screening programs
      in the developed world. Liquid-based technology has been embraced, but image
      analysis has not. The key ingredient for the NHSCSP's success is quality
      assurance. The scrutiny given to medical interventions has increased recently.
      Would the early cervical cancer cytology screening programs have passed muster if
      they had required this sort of validation? Using information from the Victorian
      Cytology Screening Services Melbourne and other Australian screening programs to
      guide its formulation, Australia's evidence-based program differs from the NHSCSP
      in several ways. The screening interval is 2 years, liquid-based technology is
      not funded, and human papillomavirus (HPV)-DNA testing for the triage of atypical
      lesions has not been sanctioned in Australia. Albrow et al allude to the possible
      introduction in the future of HPV-DNA testing as a primary screening tool. Cancer
      (Cancer Cytopathol) 2012;. (c) 2012 American Cancer Society.

PMID- 22367780
TI  - Prognostic role of KiSS-1 and possibility of therapeutic modality of metastin,
      the final peptide of the KiSS-1 gene, in urothelial carcinoma.
AB  - The KiSS-1 gene has been reported to be a metastasis suppressor gene in human
      melanoma. The gene product was isolated from human placenta as the ligand of
      GPR54, a G protein-coupled receptor, and the C-terminally amidated peptide of 54
      amino acids is called metastin. The binding of metastin to GPR54 has been shown
      to inhibit tumor metastasis in some tumor cells; however, its function remains
      unclear in urothelial carcinoma. We first evaluated KiSS-1 expression and GPR54
      expression in 151 patients with upper urinary tract urothelial carcinoma to
      determine their prognostic significance. Next, we examined the role of metastin
      in the invasiveness and lung metastasis of MBT-2 variant (MBT-2V), which is a
      highly metastatic murine bladder cancer cell. Multivariate analysis revealed that
      KiSS-1 expression was an independent predictor of metastasis and overall
      survival. However, GPR54 expression was not selected. Hematogeneous metastasis
      had a significantly lower level of KiSS-1 expression compared with lymph node
      metastasis. Metastin treatment significantly reduced the invasiveness of MBT-2V
      cells and inhibited the DNA-binding activity of NF-kappaB by blocking its nuclear
      translocation, leading to a reduction in the expression and activity of matrix
      metalloproteinase-9. Metastin treatment dramatically prevented the occurrence of
      lung metastatic nodules (6.3 +/- 2.3, n = 15) compared with controls (30.4 +/-
      5.1, n = 15; P < 0.01), as well as had survival benefit. KiSS-1 plays an
      important role in the prognosis of upper tract urothelial carcinoma and metastin
      may be an effective inhibitor of metastasis in urothelial carcinoma through its
      blockade of NF-kappaB function.

PMID- 22367781
TI  - Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts
      superior efficacy against triple-negative human breast cancer cells.
AB  - Histone deacetylase (HDAC) inhibitors (HDI) induce endoplasmic reticulum (ER)
      stress and apoptosis, while promoting autophagy, which promotes cancer cell
      survival when apoptosis is compromised. Here, we determined the in vitro and in
      vivo activity of the combination of the pan-HDI panobinostat and the autophagy
      inhibitor chloroquine against human estrogen/progesterone receptor and HER2
      (triple)-negative breast cancer (TNBC) cells. Treatment of MB-231 and SUM159PT
      cells with panobinostat disrupted the hsp90/histone deacetylase 6/HSF1/p97
      complex, resulting in the upregulation of hsp. This was accompanied by the
      induction of enhanced autophagic flux as evidenced by increased expression of
      LC3B-II and the degradation of the autophagic substrate p62. Treatment with
      panobinostat also induced the accumulation and colocalization of p62 with LC3B-II
      in cytosolic foci as evidenced by immunofluorescent confocal microscopy.
      Inhibition of panobinostat-induced autophagic flux by chloroquine markedly
      induced the accumulation of polyubiquitylated proteins and p62, caused
      synergistic cell death of MB-231 and SUM159PT cells, and inhibited mammosphere
      formation in MB-231 cells, compared with treatment with each agent alone.
      Finally, in mouse mammary fat pad xenografts of MB-231 cells, a tumor size
      dependent induction of heat shock response, ER stress and autophagy were
      observed. Cotreatment with panobinostat and chloroquine resulted in reduced tumor
      burden and increased the survival of MB-231 breast cancer xenografts.
      Collectively, our findings show that cotreatment with an autophagy inhibitor and
      pan-HDI, for example, chloroquine and panobinostat results in accumulation of
      toxic polyubiquitylated proteins, exerts superior inhibitory effects on TNBC cell
      growth, and increases the survival of TNBC xenografts.

PMID- 22367782
TI  - IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG
      type autoantibody production in autoimmune pulmonary alveolar proteinosis.
AB  - The granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb)
      is the causative agent underlying autoimmune pulmonary alveolar proteinosis
      (aPAP). It consists primarily of the IgG isotype. At present, information on
      other isotypes of the autoantibody is limited. We detected serum the IgM isotype
      of GMAb (IgM-GMAb) in more than 80% of patients with aPAP and 22% of healthy
      subjects, suggesting that a continuous antigen pressure may be present in most
      patients. Levels of the IgM isotype were weakly correlated with IgG-GMAb levels
      but not IgA-GMAb, suggesting that its production may be associated with that of
      IgG-GMAb. The mean binding avidity to GM-CSF of the IgM isotype was 100-fold
      lower than the IgG-GMAb isotype, whereas the IC(50) value for neutralizing
      capacity was 20,000-fold higher than that of IgG-GMAb, indicating that IgM-GMAb
      is only a very weak neutralizer of GM-CSF. In bronchoalveolar lavage fluid from
      nine patients, IgG-GMAb was consistently detected, but IgM-GMAb was under the
      detection limit in most patients, confirming that IgM-GMAb is functionally a
      bystander in the pathogenesis of aPAP. It rather may be involved in the mechanism
      for development of IgG-GMAb in vivo.

PMID- 22367783
TI  - Chloride secretion by cultures of pig tracheal gland cells.
AB  - Malfunction of airway submucosal glands contributes to the pathology of cystic
      fibrosis (CF), and cell cultures of CF human airway glands show defects in Cl(-)
      and water transport. Recently, a transgenic pig model of CF (the CF pig) has been
      developed. Accordingly, we have developed cell cultures of pig airway gland
      epithelium for use in investigating alterations in gland function in CF. Our
      cultures form tight junctions (as evidenced by high transepithelial electrical
      resistance) and show high levels of active anion secretion (measured as amiloride
      insensitive short-circuit current). In agreement with recent results on human
      airway glands, neurohumoral agents that elevate intracellular Ca(2+) potently
      stimulated anion secretion, while elevation of cAMP was comparatively
      ineffective. Our cultures express lactoferrin and lysozyme (serous gland cell
      markers) and MUC5B (the main mucin of airway glands). They are, therefore,
      potentially useful in determining if CF-related alterations in anion transport
      result in altered secretion of serous cell antimicrobial agents or mucus.

PMID- 22367784
TI  - Sequences of a hairpin structure in the 3'-untranslated region mediate regulation
      of human pulmonary surfactant protein B mRNA stability.
AB  - The ability of pulmonary surfactant to reduce alveolar surface tension requires
      adequate expression of surfactant protein B (SP-B). Dexamethasone (DEX, 10(-7) M)
      increases human SP-B mRNA stability by a mechanism that requires a 126-nt-long
      segment (the 7.6S region) of the 3'-untranslated region (3'-UTR). The objective
      of this study was to identify sequences in the 7.6S region that mediate
      regulation of SP-B mRNA stability. The 7.6S region was found to be sufficient for
      DEX-mediated stabilization of mRNA. Sequential substitution mutagenesis of the
      7.6S region indicates that a 90-nt region is required for DEX-mediated
      stabilization and maintenance of intrinsic stability. In this region, one 30-nt
      long element (002), predicted to form a stem-loop structure, is sufficient for
      DEX-mediated stabilization of mRNA and intrinsic mRNA stability. Cytosolic
      proteins specifically bind element 002, and binding activity is unaffected
      whether proteins are isolated from cells incubated in the absence or presence of
      DEX. While loop sequences of element 002 have no role in regulation of SP-B mRNA
      stability, the proximal stem sequences are required for DEX-mediated
      stabilization and specific binding of proteins. Mutation of the sequences that
      comprise the proximal or distal arm of the stem negates the destabilizing
      activity of element 002 on intrinsic SP-B mRNA stability. These results indicate
      that cytosolic proteins bind a single hairpin structure that mediates intrinsic
      and hormonal regulation of SP-B mRNA stability via mechanisms that involve
      sequences of the stems of the hairpin structure.

PMID- 22367785
TI  - Inhibiting NF-kappaB in the developing lung disrupts angiogenesis and
      alveolarization.
AB  - Bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy, is
      characterized by arrested alveolar development. Pulmonary angiogenesis, mediated
      by the vascular endothelial growth factor (VEGF) pathway, is essential for
      alveolarization. However, the transcriptional regulators mediating pulmonary
      angiogenesis remain unknown. We previously demonstrated that NF-kappaB, a
      transcription factor traditionally associated with inflammation, plays a unique
      protective role in the neonatal lung. Therefore, we hypothesized that
      constitutive NF-kappaB activity is essential for postnatal lung development.
      Blocking NF-kappaB activity in 6-day-old neonatal mice induced the alveolar
      simplification similar to that observed in BPD and significantly reduced
      pulmonary capillary density. Studies to determine the mechanism responsible for
      this effect identified greater constitutive NF-kappaB in neonatal lung and in
      primary pulmonary endothelial cells (PEC) compared with adult. Moreover,
      inhibiting constitutive NF-kappaB activity in the neonatal PEC with either
      pharmacological inhibitors or RNA interference blocked PEC survival, decreased
      proliferation, and impaired in vitro angiogenesis. Finally, by chromatin
      immunoprecipitation, NF-kappaB was found to be a direct regulator of the
      angiogenic mediator, VEGF-receptor-2, in the neonatal pulmonary vasculature.
      Taken together, our data identify an entirely novel role for NF-kappaB in
      promoting physiological angiogenesis and alveolarization in the developing lung.
      Our data suggest that disruption of NF-kappaB signaling may contribute to the
      pathogenesis of BPD and that enhancement of NF-kappaB may represent a viable
      therapeutic strategy to promote lung growth and regeneration in pulmonary
      diseases marked by impaired angiogenesis.

PMID- 22367787
TI  - Quality of life for patients with hypopharyngeal cancer after different
      therapeutic modalities.
AB  - BACKGROUND: Concurrent chemoradiation therapy (CCRT) and transoral laser
      microsurgery (TLM) have become therapeutic selections for organ preservation in
      patients with hypopharyngeal cancer. METHODS: Our cross-sectional, observational
      study assesses quality of life (QOL) in patients with hypopharyngeal cancers
      receiving TLM plus radiotherapy (RT) compared with those treated with CCRT only
      or radical open surgery (nearly all of whom also received RT or CCRT). QOL was
      assessed at least 6 months posttreatment. RESULTS: The study included 87
      patients. Patients receiving open surgery reported significantly more sensory and
      speech disturbances than the others and more dental problems than the TLM group;
      the CCRT group experienced more xerostomia than the others, more weight loss, and
      dysphagia than the open surgery group; TLM patients experience fewer difficulties
      in emotional and social functioning, financial impact, and cough. CONCLUSION: TLM
      may provide comparable, if not better, QOL for patients relative to the other
      therapeutic regimens for selective advanced cases of hypopharyngeal cancer.

PMID- 22367788
TI  - Stabilization of G-quadruplex DNA, inhibition of telomerase activity and live
      cell imaging studies of chiral ruthenium(II) complexes.
AB  - Telomerase inhibition is an attractive strategy for cancer chemotherapy. In the
      current study, we have synthesized and characterized two chiral ruthenium(II)
      complexes, namely, Lambda-[Ru(phen)(2)(p-MOPIP)](2+) and Delta-[Ru(phen)(2)(p
      MOPIP)](2+), where phen is 1,10-phenanthroline and p-MOPIP is 2-(4-methoxyphenyl)
      imidazo[4,5f][1,10]phenanthroline. The chiral selectivity of the compounds and
      their ability to discriminate quadruplex DNA were investigated by using UV/Vis,
      fluorescence spectroscopy, circular dichroism spectroscopy, fluorescence
      resonance energy transfer melting assay, polymerase chain reaction stop assay and
      telomerase repeat amplification protocol. The results indicate that the two
      chiral compounds could induce and stabilize the formation of antiparallel G
      quadruplexes of telomeric DNA in the presence or absence of metal cations. We
      report the remarkable ability of the two complexes Lambda-[Ru(phen)(2)(p
      MOPIP)](2+) and Delta-[Ru(phen)(2)(p-MOPIP)](2+) to stabilize selectively G
      quadruplex DNA; the former is a better G-quadruplex binder than the latter. The
      anticancer activities of these complexes were evaluated by using the MTT assay.
      Interestingly, the antiproliferative activity of Lambda-[Ru(phen)(2)(p
      MOPIP)](2+) was higher than that of Delta-[Ru(phen)(2)(p-MOPIP)](2+), and Lambda
      [Ru(phen)(2)(p-MOPIP)](2+) showed a significant antitumor activity in HepG2
      cells. The status of the nuclei in Lambda/Delta-[Ru(phen)(2) (p-MOPIP)](2+)
      treated HepG2 cells was investigated by using real-time living cell microscopy to
      determine the effects of Lambda/Delta-[Ru(phen)(2)(p-MOPIP)](2+) on intracellular
      accumulation. The results show that Lambda/Delta-[Ru(phen)(2)(p-MOPIP)](2+) can
      be taken up by HepG2 cells and can enter into the cytoplasm as well as accumulate
      in the nuclei; this suggests that the nuclei were the cellular targets of
      Lambda/Delta-[Ru(phen)(2)(p-MOPIP)](2+).

PMID- 22367789
TI  - Impulse control disorders in obese patients.
AB  - The aim of this study was to determine the prevalence of impulse control
      disorders (ICDs) in morbidly obese individuals. One hundred bariatric surgery
      candidates were examined using a module of the Structured Clinical Interview for
      DSM-IV that has been developed for ICDs. Nineteen per cent suffered from at least
      one current ICD and 27% met the criteria for any lifetime ICD, most frequently
      skin picking (current, 8%; lifetime, 9%), compulsive buying (current 6%, lifetime
      8%), and intermittent explosive disorder (current, 5%; lifetime, 10%). Patients
      with regular binge eating (N = 25) reported significantly more often a history of
      at least one ICD compared with those without binge eating. The results indicate a
      high prevalence of ICDs among morbidly obese prebariatric surgery patients that
      are related to regular binge eating.

PMID- 22367786
TI  - Characterization of the Niemann-Pick C pathway in alveolar type II cells and
      lamellar bodies of the lung.
AB  - The Niemann-Pick C (NPC) pathway plays an essential role in the intracellular
      trafficking of cholesterol by facilitating the release of lipoprotein-derived
      sterol from the lumen of lysosomes. Regulation of cellular cholesterol
      homeostasis is of particular importance to lung alveolar type II cells because of
      the need for production of surfactant with an appropriate lipid composition. We
      performed microscopic and biochemical analysis of NPC proteins in isolated rat
      type II pneumocytes. NPC1 and NPC2 proteins were present in the lung, isolated
      type II cells in culture, and alveolar macrophages. The glycosylated and
      nonglycosylated forms of NPC1 were prominent in the lung and the lamellar body
      organelles. Immunocytochemical analysis of isolated type II pneumocytes showed
      localization of NPC1 to the limiting membrane of lamellar bodies. NPC2 and
      lysosomal acid lipase were found within these organelles, as confirmed by z-stack
      analysis of confocal images. All three proteins also were identified in small,
      lysosome-like vesicles. In the presence of serum, pharmacological inhibition of
      the NPC pathway with compound U18666A resulted in doubling of the cholesterol
      content of the type II cells. Filipin staining revealed a striking accumulation
      of cholesterol within lamellar bodies. Thus the NPC pathway functions to control
      cholesterol accumulation in lamellar bodies of type II pneumocytes and, thereby,
      may play a role in the regulation of surfactant cholesterol content.

PMID- 22367790
TI  - Development of stable HSPA1A promoter-driven luciferase reporter HepG2 cells for
      assessing the toxicity of organic pollutants present in air.
AB  - HSPA1A (HSP70-1) is a highly inducible heat shock gene up-regulated in response
      to environmental stresses and pollutants. The aim of our study was to evaluate
      the sensitivity of the stable metabolically competent HepG2 cells containing a
      human HSPA1A promoter-driven luciferase reporter (HepG2-luciferase cells) for
      assessing the toxicity of organic pollutants present in air. The HepG2-luciferase
      cells were validated by heat shock treatment and testing three organic compounds
      (pyrene, benzo[a]pyrene, and formaldehyde) that are ubiquitous in the air. The
      maximal level of HSPA1A (HSP70-1) and relative luciferase activity induced by
      heat shock were over three and nine times the control level, respectively.
      Pyrene, benzo[a]pyrene, and formaldehyde all induced significantly elevated
      levels of relative luciferase activity in a dose-dependent manner. Extractable
      organic matter (EOM) from urban traffic and coke oven emissions in ambient air
      were tested on the HepG2-luciferase cells. The traffic EOM induced significant
      increase in relative luciferase activity at concentrations of picogram per liter.
      The coke oven EOM produced a strong dose-dependent induction of relative
      luciferase activity up to six times the control value. Significant increases in
      relative luciferase activity were observed at concentrations that were as low, or
      lower than the concentrations that the tested organic pollutants decreased cell
      viability, and increased malondialdehyde concentration, Olive tail moment, and
      micronuclei frequency. Therefore, we conclude that the HepG2-luciferase cells are
      a valuable tool for rapid screening of the overall toxicity of organic pollutants
      present in air.

PMID- 22367791
TI  - Urinary metabonomic study using a CUMS rat model of depression.
AB  - Chronic unpredictable mild stress (CUMS) is a well-validated model of depression.
      In this study, a urinary metabonomics method based on the NMR spectrometry was
      used to study the metabolic perturbation in CUMS-induced rat depression model.
      With pattern recognition analysis, a clear separation of CUMS rats and healthy
      controls was achieved, and nine endogenous metabolites contributing to the
      separation were identified. CUMS-treated rats were characterized by the increase
      of glycine, pyruvate, glutamine, and asparagines, as well as the decrease of 2
      oxoglutarate, dimethylglycine, citrate, succinate, and acetate. The urinary
      biochemical changes related to the metabolic disturbance in CUMS induced
      depression, and the possible correlations with live qi stagnation in traditional
      Chinese medicine are discussed. The work shows that CUMS is a reliable model for
      studying depression, and the noninvasive urinary metabolomic method is a valuable
      tool to investigate the biochemical pertubations in depression as an early
      diagnostic means.

PMID- 22367793
TI  - Commentary on "Cervical cancer screening in England: the past, present, and
      future": a comparison with Canada.
AB  - For cervical cancer screening to be most effective, all eligible women in the
      population must be enrolled in an organized program. In this issue, Albrow et al
      describe how cervical cancer screening in England migrated from "opportunistic"
      in the 1960s to "organized" in the 1980s and discuss its continued evolution as
      new screening approaches and technologies developed. England's current National
      Health Services Cervical Screening Programme is the poster child for organized
      screening delivery. A similar model of central coordination and peripheral
      delivery of screening does not exist in Canada. The provision of health services
      is under provincial jurisdiction, and consequently each province administers its
      own version of a cervical cancer screening program. To date, organized screening
      has only been achieved in 2 of 10 provinces, and screening elsewhere is
      opportunistic. Screening in Canada begins at age 18-21, ends at age 69-70, and
      mostly occurs annually. This approach has yielded a significant reduction in
      cervical cancer incidence and mortality, but health service utilization costs
      have been high. The future should see full implementation of organized screening
      in all provinces, and when combined with the publicly funded human papillomavirus
      vaccination program of young girls begun in 2008, the result should be even
      better cancer control. Cancer (Cancer Cytopathol) 2012;. (c) 2011 American Cancer
      Society.

PMID- 22367792
TI  - The histone deacetylase inhibitor, romidepsin, suppresses cellular immune
      functions of cutaneous T-cell lymphoma patients.
AB  - Romidepsin is the second histone deacetylase inhibitor (HDACi) approved for the
      treatment of advanced stages of cutaneous T-cell lymphoma (CTCL). Recent in vitro
      data suggest that HDACis suppress immune function although these findings have
      not been confirmed in patients. Thus, we serially examined the cellular immune
      function of eight CTCL patients undergoing treatment with three cycles of
      romidepsin. We measured the patients' natural killer (NK) and dendritic cell (DC)
      function and performed an in vitro terminal deoxynucleotidyl transferase dUTP
      nick end labeling assay to measure cellular apoptosis. Patients' NK cell
      cytolytic activity decreased from baseline to the third cycle of treatment (P =
      0.018) but stimulation with a toll-like receptor (TLR) agonist increased this
      activity (P = 0.018). At baseline, a TLR agonist could both activate patients' DC
      (P = 0.043) and stimulate interleukin-12 protein production (P = 0.043) but both
      were suppressed after the first cycle of romidepsin. Finally, we observed
      increased specificity for romidepsin-induced CD4+ tumor cell apoptosis and dose
      dependent increases in cellular apoptosis of healthy cells in multiple lineages
      (P < 0.05). These findings raise concern that HDACis suppress immune function in
      CTCL patients and they support the concurrent use of multiple immune stimulatory
      agents to preserve the host immune response.

PMID- 22367794
TI  - Prospective randomized trial of preoperative enteral immunonutrition followed by
      elective total gastrectomy for gastric cancer.
AB  - BACKGROUND: Perioperative enteral immunonutrition is thought to reduce
      postoperative morbidity in patients undergoing major gastrointestinal surgery.
      This study assessed the clinical effects of preoperative enteral immunonutrition
      in well nourished patients with gastric cancer undergoing total gastrectomy.
      METHODS: Well nourished patients with primary gastric cancer, fit for total
      gastrectomy, were randomized to either a control group with regular diet, or an
      immunonutrition group that received regular diet supplemented with 1000 ml/day of
      immunonutrients for 5 consecutive days before surgery. The primary endpoint was
      the incidence of surgical-site infection (SSI). Secondary endpoints were rates of
      infectious complications, overall postoperative morbidity and C-reactive protein
      (CRP) levels on 3-4 days after surgery. RESULTS: Of 244 randomized patients, 117
      were allocated to the control group and 127 received immunonutrition. SSIs
      occurred in 27 patients in the immunonutrition group and 23 patients in the
      control group (risk ratio (RR) 1.09, 95 per cent confidence interval 0.66 to
      1.78). Infectious complications were observed in 30 patients in the
      immunonutrition group and 27 in the control group (RR 1.11, 0.59 to 2.08). The
      overall postoperative morbidity rate was 30.8 and 26.1 per cent respectively (RR
      1.18, 0.78 to 1.78). The median CRP value was 11.8 mg/dl in the immunonutrition
      group and 9.2 mg/dl in the control group (P = 0.113). CONCLUSION: Five-day
      preoperative enteral immunonutrition failed to demonstrate any clear advantage in
      terms of early clinical outcomes or modification of the systemic acute-phase
      response in well nourished patients with gastric cancer undergoing elective total
      gastrectomy. REGISTRATION NUMBER: ID 000000648 (University Hospital Medical
      Information Network (UMIN) database).

PMID- 22367795
TI  - Principles of scarce medical resource allocation in natural disaster relief: a
      simulation approach.
AB  - BACKGROUND: A variety of triage principles have been proposed. The authors sought
      to evaluate their effects on how many lives can be saved in a hypothetical
      disaster. OBJECTIVE: To determine an optimal scarce resource-rationing principle
      in the emergency response domain, considering the trade-off between lifesaving
      efficiency and ethical issues. METHOD: A discrete event simulation model is
      developed to examine the efficiency of four resource-rationing principles: first
      come-first served, random, most serious first, and least serious first. Seven
      combinations of available resources are examined in the simulations to evaluate
      the performance of the principles under different levels of resource scarcity.
      RESULT: The simulation results indicate that the performance of the medical
      resource allocation principles is related to the level of the resource scarcity.
      When the level of the scarcity is high, the performances of the four principles
      differ significantly. The least serious first principle performs best, followed
      by the random principle; the most serious first principle acts worst. However,
      when the scarcity is relieved, there are no significant differences among the
      random, first come-first served, and least serious first principles, yet the most
      serious first principle still performs worst. CONCLUSION: Although the least
      serious first principle exhibits the highest efficiency, it is not ethically
      flawless. Considering the trade off between the lifesaving efficiency and the
      ethical issues, random selection is a relatively fair and efficient principle for
      allocating scarce medical resources in natural disaster responses.

PMID- 22367796
TI  - The neurotrophin family of neurotrophic factors: an overview.
AB  - The neurotrophins are a family of closely related proteins that were first
      identified as survival factors for sympathetic and sensory neurons and have since
      been shown to control a number of aspects of survival, development, and function
      of neurons in both the central and peripheral nervous systems. Limiting
      quantities of neurotrophins during development control the numbers of surviving
      neurons to ensure a match between neurons and the requirement for a suitable
      density of target innervation. Biological effects of each of the four mammalian
      neurotrophins are mediated through activation of one or more of the three members
      of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases
      (TrkA, TrkB, and TrkC). In addition, all neurotrophins activate the p75
      neurotrophin receptor, a member of the tumor necrosis factor receptor
      superfamily. Neurotrophin engagement of Trk receptors leads to activation of Ras,
      phosphatidylinositol 3-kinase, phospholipase C-gamma1, and signaling pathways
      controlled through these proteins, including the mitogen-activated protein
      kinases. Neurotrophin availability is required into adulthood, where they control
      synaptic function and plasticity and sustain neuronal cell survival, morphology,
      and differentiation. This chapter will provide an overview of neurotrophin
      biology, their receptors, and signaling pathways.

PMID- 22367797
TI  - Neuronal growth-promoting and inhibitory cues in neuroprotection and
      neuroregeneration.
AB  - During development of the nervous system, neurons extend axons over considerable
      distances in a highly stereospecific fashion in order to innervate their targets
      in an appropriate manner. This involves the recognition, by the axonal growth
      cone, of guidance cues that determine the pathway taken by the axons. These
      guidance cues can act to promote and/or repel growth cone advance. The directed
      growth of axons is partly governed by cell adhesion molecules (CAMs) on the
      neuronal growth cone that bind to CAMs on the surface of other axons or
      nonneuronal cells. In vitro assays have established the importance of the CAMs
      ((neural cell adhesion molecule NCAM), N-cadherin, and L1) in promoting axonal
      growth over cells. Compelling evidence implicates the fibroblast growth factor
      receptor tyrosine kinase as the primary signal transduction molecule in the CAM
      pathway. CAMs are important constituents of synapses, and they appear to play
      important and diverse roles in regulating synaptic plasticity associated with
      learning and memory. Synthetic NCAM peptide mimetics corresponding to the binding
      site of NCAM for the fibroblast growth factor receptor promote synaptogenesis,
      enhance presynaptic function, and facilitate memory consolidation. Dimeric
      versions of functional binding motifs of N-cadherin behave as N-cadherin
      agonists, promoting both neuritogenesis and neuronal cell survival. Negative
      extracellular signals that physically direct neurite growth have also been
      described. The latter include the myelin inhibitory proteins, Nogo, myelin
      associated glycoprotein, and oligodendrocyte-myelin glycoprotein. Potentiation of
      outgrowth-promoting signals, together with antagonism of myelin proteins or their
      convergent receptor, NgR, and its second messenger pathways, may provide new
      opportunities in the rational design of treatments for acute brain injury and
      neurodegenerative disorders.

PMID- 22367798
TI  - Culture of rat cerebellar granule neurons and application to identify
      neuroprotective agents.
AB  - In primary culture of the early postnatal cerebellum, glutamatergic granule cells
      are highly enriched and recapitulate many properties characteristic of developing
      granule neurons in vivo. For example, withdrawal of K(+) from differentiated rat
      primary cerebellar granule neurons results in the apoptotic death of the majority
      of cells after 48 h. Removal of cerebellar granule neurons from depolarizing
      culture conditions with high K(+) is thought to reflect the regulation of trophic
      action of neuronal activity and has found widespread application as a model for
      studying the mechanisms of survival factor withdrawal-induced neuronal cell
      apoptosis and the neuroprotective action of trophic agents. This chapter presents
      a protocol for the culture of postnatal rat cerebellar granule neurons and
      results in a preparation containing 95% glutamatergic granule cells and its
      application to the evaluation of corticotropin receptor agonists as
      neuroprotective agents.

PMID- 22367799
TI  - Isolation and culture of neural progenitor cells from rat postnatal cerebellum.
AB  - The mammalian brain contains undifferentiated, mitotically active, and
      multipotent neural stem/progenitor cells that in vivo contribute new neurons and
      glia to specific areas of the mature brain. When isolated under the appropriate
      conditions, these cells maintain in vitro the ability to proliferate and
      differentiate into cells that express neuronal and glial markers. Neural
      stem/progenitor cells have been identified and isolated from many regions of the
      embryonic, postnatal, and adult central nervous system, including cerebellum.
      This chapter details techniques to isolate and culture neural progenitor cells
      from rat postnatal cerebellum, which can be used as an in vitro model to study
      the molecular mechanisms underlying proliferation and differentiation into mature
      neural cells induced by various stimuli including pharmacological agents.

PMID- 22367800
TI  - Culture of rodent cortical and hippocampal neurons.
AB  - Neurons cultured from rodent central nervous system tissues represent an
      important tool in the study of neurodegenerative disease mechanisms and
      neuroregenerative processes, including the survival- and axon growth-promoting
      properties of neurotrophic factors. This chapter presents a detailed protocol for
      the preparation of rat and mouse cortical and hippocampal neuron cell cultures
      using either embryonic or postnatal tissue with enzymatic digestion.

PMID- 22367801
TI  - Amyloid beta-peptide neurotoxicity assay using cultured rat cortical neurons.
AB  - Neurons cultured from rodent central nervous system tissues represent an
      important tool in the study of neurodegenerative disease mechanisms and
      neuroregenerative processes, including the survival- and axon growth-promoting
      properties of neurotrophic factors. This chapter presents a detailed protocol for
      the preparation of rat and mouse cortical and hippocampal neuron cell cultures,
      using either embryonic or postnatal tissue.

PMID- 22367802
TI  - Culture of neonatal rodent microglia, astrocytes, and oligodendrocytes from
      cortex and spinal cord.
AB  - The protocol described in this chapter covers the preparation and culture of
      enriched populations of microglia, astrocytes, and oligodendrocytes from the
      cortex and spinal cord of neonatal rat and mouse. The procedure is based on the
      enzymatic digestion of tissue, followed by the culture of a mixed glial cell
      population which is then utilized as the starting point for the isolation, via
      differential attachment, of the different cell types.

PMID- 22367803
TI  - Central nervous system neuron-glia co-culture models.
AB  - Glial cell activation plays an important role in the pathogenesis of various
      neurodegenerative disorders. This article presents a protocol for the preparation
      of cultures consisting of rat embryonic cortical neurons grown in the presence of
      cortical microglia, in which the glia are present in physical contact with the
      neurons or separated by a semi-permeable membrane barrier.

PMID- 22367804
TI  - Culture and characterization of rat mesencephalic dopaminergic neurons.
AB  - Dopaminergic neuronal cell degeneration is the principal characteristic feature
      of the neuropathology of Parkinson's disease. Cultures of mesencephalic neurons
      are widely used as a source of dopaminergic neurons for the study of mechanisms
      implicated in dopaminergic cell death and for the evaluation of potential
      dopaminergic neuroprotective agents, including neurotrophic factors. This chapter
      presents a detailed protocol for the preparation of rat mesencephalic cell
      cultures and their application to evaluating the neuroprotective action of brain
      derived neurotrophic factor.

PMID- 22367805
TI  - Preparation of adult spinal cord motor neuron cultures under serum-free
      conditions.
AB  - Spinal cord motor neuron cultures are an important tool for the study of
      mechanisms involved in motor neuron survival, degeneration and regeneration,
      volatile anesthetic-induced immobility, motor neuron disorders such as
      amyotrophic lateral sclerosis or spinal muscular atrophy as well as in spinal
      cord injury. Embryonic spinal cord motor neurons derived from rats have been
      successfully cultured; unfortunately, the culture of adult motor neurons has been
      problematic due to their short-term survival. Recently, by using a cocktail of
      target-derived factors, neurotrophins (brain-derived neurotrophic factor and
      glial cell line-derived neurotrophic factor) and a permeable cyclic adenosine
      monophosphate analog, we have established a reproducible protocol for long-term
      cultures of healthy and functional adult motor neurons (Exp Neurol 220:303-315,
      2009). Here, we now describe in detail the steps that we used for the
      optimization of the process of isolation and maintenance of adult rat ventral
      horn motor neurons in vitro.

PMID- 22367806
TI  - Rodent retinal ganglion cell cultures.
AB  - Central neurons lose the ability for axonal regrowth during development and
      typically do not regenerate their axons following axotomy once they become mature
      unless given a growth-permissive environment, for example, a peripheral nerve
      graft. Retinal ganglion cells (RGCs) of the optic nerve represent a highly useful
      cell model for the study of neurotrophic factor responsiveness, although the
      presence of nonneuronal cells in the retina makes it difficult to interpret the
      direct effects of tested factors on RGCs. Cultures of purified RGCs thus
      represent an excellent tool for the study of optic nerve cell trophic
      responsiveness, in terms of both survival and axonal regeneration.

PMID- 22367807
TI  - Culture of purified glial cell populations from optic nerve.
AB  - Glial cells play a key role in nervous system function, providing neurotrophic
      factor support to neurons as well as taking part in two-way neuron-glia signaling
      (e.g., neurotransmitter release). White matter-derived glia are important in
      certain neurodegenerative diseases involving axonal loss, for example in multiple
      sclerosis. Here we describe procedures for the preparation and culture of mixed
      nerve cells from postnatal rat optic nerve, followed by protocols which can serve
      for the purification of individual populations of glia from this tissue, namely
      O2A progenitors and oligodendrocytes, and astrocytes and astrocyte precursors.

PMID- 22367808
TI  - Isolation and culture of rat cone photoreceptor cells.
AB  - In retinal diseases characterized by photoreceptor degeneration, the main cause
      of clinically significant vision loss is cone, rather than rod, loss.
      Photoreceptor apoptosis can be affected by the availability and/or delivery of
      neurotrophic proteins, and cultures of photoreceptors are valuable for studying
      these processes. In the present study, a technique was designed to purify cones
      to make it possible to screen for neuroprotective molecules. The present chapter
      describes a technique for preparing cultures of purified rat retina cone
      photoreceptors based upon panning with peanut agglutinin lectin, which
      selectively binds to cones. In addition, we describe a protocol for the
      purification and culture of retinal pigmented epithelial cells from postnatal
      rat.

PMID- 22367809
TI  - Culture of rat retina pigmented epithelial cells.
AB  - Retinal pigment epithelium cells play a key role in maintaining the normal
      function of retina and can express several neurotrophic factors, which support
      the neurosensory retina and may also provide trophic signals to the host
      dopaminergic neurons. The following chapter describes a protocol for the
      purification and culture of retinal pigmented epithelial cells from postnatal
      rat.

PMID- 22367810
TI  - Mammalian growth cone turning assays identify distinct cell signalling mechanisms
      that underlie axon growth, guidance and regeneration.
AB  - The cell signalling mechanisms underlying mammalian central nervous system axon
      growth and guidance change during development, such that axons that establish
      appropriate connectivity in the embryo fail to regenerate after injury to the
      adult nervous system. The growth cone turning assay has been used in Xenopus
      neurons to elucidate mechanisms of axon guidance during development. Here, we
      describe how we have adapted this assay for rat dorsal root ganglion neurons to
      study the influence of extracellular secreted factors causing growth cone
      attraction and repulsion. Additionally, we describe how this method can be
      combined with small interfering RNA and cDNA transfections to manipulate protein
      expression in growth cones, and fluorescence resonance energy transfer to monitor
      the activity of signalling pathways in live neurons. This assay provides the
      unique ability to manipulate and visualise the internal status of growth cone
      signalling whilst challenged with extracellular chemotropic signalling molecules,
      and can be used to develop strategies to promote axon regeneration in the mature
      mammalian central nervous system.

PMID- 22367811
TI  - Culture of dissociated sensory neurons from dorsal root ganglia of postnatal and
      adult rats.
AB  - The development of new therapeutics for management of pain is likely to become
      much more mechanism based, and therefore, we need a more thorough understanding
      of the different pain development pathways. The afferent fibers of sensory
      neurons, with their cell bodies in the dorsal root ganglia (DRG), are thought to
      be key in pain mechanisms. DRG neurons can be prepared from embryonic, postnatal,
      or adult tissue. Embryonic preparations have the advantage of higher cell yields
      and greater proportion of neurons, but they are dependent on neurotrophins for
      the first week of culture. In contrast, dissociated postnatal and adult DRG
      sensory neurons offer the possibility to study mature neurons that may better
      resemble the in vivo characteristics of these cells. Here, we describe the
      dissociation of DRG sensory neurons from postnatal and adult rats. DRG are
      dissected and dissociated using a prolonged trypsin/collagenase treatment,
      followed by mechanical separation of the neurons. We have routinely prepared them
      for electrophysiological studies by the methods outlined in this chapter and
      describe some of the pitfalls that we have encountered, with hints of how to
      overcome them.

PMID- 22367812
TI  - Culture and proliferation of highly purified adult Schwann cells from rat, dog,
      and man.
AB  - This chapter presents fast and easy protocols to obtain highly purified cultures
      of proliferating adult rat, canine, and human Schwann cells. Cell preparation
      from predegenerated adult sciatic nerves combined with the use of melanocyte
      growth medium supplemented with forskolin, fibroblast growth factor-2, pituitary
      extract, and heregulin as selective, serum-free culture medium and two methods
      for a consecutive cell-enrichment step are described. Our protocols result in
      approximately 90% pure Schwann cell cultures (or higher). The average time to
      obtain highly purified in vitro cultures of adult Schwann cells is 21 days.

PMID- 22367813
TI  - Use of PC12 cells and rat superior cervical ganglion sympathetic neurons as
      models for neuroprotective assays relevant to Parkinson's disease.
AB  - Cellular models composed of primary neuronal cultures or neuron-like cell lines
      are commonly used to study neuron cell death and to test the neuroprotective
      properties of specific compounds. Cellular models are easily accessible,
      permitting dissection and modulation of signaling pathways involved in neuron
      death. For example, drug or shRNA delivery is more straightforward since there is
      no blood-brain barrier to cross. However, since these models have their
      limitations, any important findings should ultimately be verified with animal
      models and human samples. Here, we describe two cellular models that can be used
      as a highly informative and easy to use starting point for testing potential
      neuroprotective drugs for Parkinson's disease: PC12 cells and sympathetic
      neuronal cell cultures. We describe in detail the protocols needed to apply these
      models to study neuroprotection in the context of Parkinson's disease.

PMID- 22367814
TI  - Compartmented chambers for studying neurotrophic factor action.
AB  - Neurotrophic factors released by target tissues maintain the survival and
      differentiation of innervating neurons. The manner by which these target-derived
      neurotrophic proteins communicate with innervating neurons has been actively
      pursued for over three decades. The present chapter describes a technique for
      preparing and maintaining compartmented chambers for culturing neurons derived
      from either superior cervical ganglia (sympathetic neurons) or dorsal root
      ganglia (sensory neurons). This system recapitulates the selective stimulation of
      neuron terminals that occurs in vivo following release of target-derived
      neurotrophins.

PMID- 22367815
TI  - Preparation and culture of adrenal chromaffin cells.
AB  - Cultured chromaffin cells have been used for almost 40 years in the study of
      different cell functions using biochemical, electrophysiological,
      pharmacological, and toxicological approaches. Chromaffin cells are essentially
      secretory cells that are used to model sympathetic neurons or neuroendocrine
      cells. In this chapter, we describe the most common methods currently used to
      isolate and culture chromaffin cells from the animals used most commonly: cows,
      rats, and mice. We also provide some advice on the use of these cells in the
      laboratory.

PMID- 22367816
TI  - Indirect immunofluorescence staining of cultured neural cells.
AB  - Immunofluorescence is a technique allowing the visualization of a specific
      protein or antigen in cells or tissue sections by binding a specific antibody
      chemically conjugated with a fluorescent dye such as fluorescein isothiocyanate.
      There are two major types of immunofluorescence staining methods: (1) direct
      immunofluorescence staining in which the primary antibody is labeled with
      fluorescence dye and (2) indirect immunofluorescence staining in which a
      secondary antibody labeled with fluorochrome is used to recognize a primary
      antibody. This chapter describes procedures for the application of indirect
      immunofluorescence staining to neural cells in culture.

PMID- 22367817
TI  - Neurite outgrowth assessment using high content analysis methodology.
AB  - High content analysis of neurite outgrowth enables the rapid and comprehensive
      phenotypic assessment of individual neurons in a multiwell format amenable to
      high throughput assays. The resulting data are considered "high content" because
      multiple measurements of neuronal outgrowth and morphometric data are calculated
      from hundreds of individual cells within each image. This approach has been
      widely adopted by the pharmaceutical industry to accelerate neurological drug
      discovery and in vitro safety assessment. High content technology utilizes
      automated fluorescent and/or brightfield microscopy for image acquisition. The
      acquired images are then quantified using mathematical algorithms to measure
      pertinent neurobiological morphometric information, including neurite length,
      count, and extent of branching for each cell within the images. Furthermore,
      evaluation of the individual cell-level measurements enables the detection of
      subpopulations of cellular responders not apparent when examining well-level
      averages. Using this technology, neurite outgrowth can be quantified in each
      well, derived from hundreds of cell measurements in a 96-well microplate in
      approximately 30 min.

PMID- 22367818
TI  - Dissociated cell culture for testing effects of carbon nanotubes on neuronal
      growth.
AB  - Cell culture has emerged as an important research method for studying the effects
      of carbon nanotubes (CNTs) on primary neurons. We describe the procedure for
      preparation of dissociated mixed cell culture from postnatal rat hippocampi.
      Based on morphological criteria and specific neuronal cell markers, neurons can
      be selected within this mixed cell culture and studied. We present the procedure
      for the assessment of neuronal cell morphology based on intracellular
      fluorescence of the vital dye calcein that accumulates in live neurons. This
      procedure encompasses fluorescence imaging and measurement of the following
      parameters: neurite number, total neurite length, mean neurite length, number of
      growth cones, number of branches, and number of branches per neurite. These
      combined cell culture and fluorescence microscopy approaches can be successfully
      used for assessment of the effects that CNTs, as water-soluble agents, have on
      neuronal cell growth and neurite outgrowth.

PMID- 22367819
TI  - High-resolution imaging and evaluation of spines in organotypic hippocampal slice
      cultures.
AB  - Dendritic spines act as sites of excitatory neuronal input in many types of
      neurons. Spine shape correlates with the strength and maturity of synaptic
      contacts. Thus, evaluation of spine morphology is relevant for studies on
      neuronal development, for determination of morphological correlates of learning
      and memory, and for analysis of mechanisms of neurodegeneration. Here, we
      describe a method to determine spine morphology in an ex vivo model of
      organotypic hippocampal slice cultures prepared from transgenic or non-transgenic
      mice. Spines are imaged using confocal high-resolution imaging and evaluated by
      algorithm-based analysis. The approach permits semiautomated determination of
      spine density and classification of different spine types in dendritic segments
      from hippocampal subregions to evaluate intrahippocampal connectivity.

PMID- 22367820
TI  - Imaging amyloid precursor protein in vivo: an axonal transport assay.
AB  - Fusion of fluorescent probes to axonally transported proteins represents an
      established approach that enables live imaging of axonal transport. In this
      approach, in vivo examination of fluorescent particle dynamics provides
      information about the length, directionality, and the velocity by which axonally
      transported proteins travel along axons. Analysis of these parameters provides
      information about the distribution of axonal proteins and their dynamics in and
      between different subcellular compartments. Establishing the movement behavior of
      amyloid precursor protein within axons indicated that live imaging approaches
      offer the opportunity to significantly enhance our understanding of the biology
      as well as pathology of axonal transport. This chapter provides a fluorescence
      based procedure for measuring axonal transport of APP in cultured newborn mouse
      hippocampal neurons.

PMID- 22367821
TI  - The use of specific AAV serotypes to stably transduce primary CNS neuron
      cultures.
AB  - Although primary neuronal cell cultures are a valuable source of in vitro insight
      for many neurobiologists, all current gene expression technologies for these
      cells have significant drawbacks. Some of these limitations of current gene
      expression protocols include toxicity, transient expression, a requirement for
      postnatal neurons, and/or low efficiency. To date, many types of experiments were
      not possible because of these limitations. Here, we outline a methodology by
      which primary cultured neurons can be transduced at any age, after plating, with
      virtually no toxicity and continued gene expression for the lifetime of the
      culture. This method involves the use of adeno-associated viral vectors, which
      have the potential to be highly useful for either upregulation or downregulation
      of single or multiple genes, including neurotrophins, other neuroprotective
      genes, and neurotoxins.

PMID- 22367822
TI  - Preparation and characterization of biocompatible chitosan nanoparticles for
      targeted brain delivery of peptides.
AB  - Here, we describe a nanocarrier system that can transfer chitosan nanoparticles
      loaded with either small peptides such as the caspase inhibitor Z-DEVD-FMK or a
      large peptide like basic fibroblast growth factor across the blood-brain barrier.
      The nanoparticles are selectively directed to the brain and are not measurably
      taken up by liver and spleen. Intravital fluorescent microscopy provides an
      opportunity to study the penetration kinetics of nanoparticles loaded with
      fluorescent agents such as Nile red, and has demonstrated that this nanomedicine
      formulation is rapidly transported across the blood-brain barrier.

PMID- 22367823
TI  - [3H]serotonin release assay using antigen-stimulated rat peritoneal mast cells.
AB  - The concentration of nerve growth factor (NGF) is elevated in a number of
      inflammatory and autoimmune states in conjunction with increased accumulation of
      mast cells. Mast cells, which are of hematopoietic lineage, and NGF appear to be
      involved in neuroimmune interactions and tissue inflammation. Mast cells
      themselves are capable of producing and responding to NGF. Here we describe a
      protocol for the isolation and culture of peritoneal-derived rat mast cells,
      together with a [(3)H]serotonin release assay which is useful in assessing the
      effects of antigens and neurotrophic factors on mast-cell activation.

PMID- 22367824
TI  - Rat hippocampal slice culture models for the evaluation of neuroprotective
      agents.
AB  - Organotypic slices cultured for weeks in vitro represent an extremely valuable
      strategy for the investigation of the long-term properties of neuronal circuits
      under physiological and pathological conditions. Here, we describe how to prepare
      rat organotypic hippocampal slice cultures and how to expose them for appropriate
      periods of time to excitotoxic agents or to oxygen and glucose deprivation
      conditions, in order to mimic the pattern of pyramidal cell damage which is
      observed in vivo and in other in vitro models. This preparation is very useful
      not only to study synaptic plasticity or the pathways and mechanisms of
      neurodegeneration but also to evaluate the effects of neuroprotective agents.

PMID- 22367825
TI  - A 6-hydroxydopamine in vivo model of Parkinson's disease.
AB  - Animal models of Parkinson's disease are essential to explore pathophysiological
      hypotheses and to test new treatment options, including neurotrophic factors.
      Catecholaminergic neurotoxins used to generate such models are 6-hydroxydopamine
      and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These neurotoxins predominantly
      kill dopaminergic neurons through oxidative damage and mitochondrial failure,
      although 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine fails to induce a
      significant dopaminergic neurodegeneration in rats. The present chapter describes
      a protocol for the 6-hydroxydopamine rat model based on stereotaxic injection
      performed only unilaterally, which mimics an early-to-mid stage of the disease.

PMID- 22367826
TI  - Brain microdialysis in freely moving animals.
AB  - Brain microdialysis is an analytical technique used for the dynamic monitoring of
      brain neurochemistry in awake, freely moving animals. This technique requires the
      insertion of a small dialysis catheter, called a microdialysis probe, into a
      specific brain region, and its perfusion with an artificial extracellular fluid.
      The microdialysate samples, obtained from the probe outlet, can be analysed using
      high-performance liquid chromatography with electrochemical detection for the
      quantification of oxidizable molecules recovered from the extracellular space. In
      this chapter, we describe a protocol for performing a microdialysis setup and
      experiment in freely moving rats and mice. Furthermore, the high-performance
      liquid chromatographic determination of ascorbic acid, uric acid, catecholamines,
      indolamines and derivatives is described in detail.

PMID- 22367827
TI  - Evaluating motor neuron death in neonatal rats subjected to sciatic nerve lesion.
AB  - Neonatal sciatic nerve lesion is a useful experimental model for the study of
      neuronal cell death. Sciatic nerve transection or crush is the most frequently
      used approach to evaluate motoneuron loss in the lumbar enlargement of the spinal
      cord. Here we describe and illustrate the surgical procedures performed in our
      laboratory to assess motoneuron cell death and the related cellular mechanisms.

PMID- 22367828
TI  - Rodent spinal cord injury model and application of neurotrophic factors for
      neuroprotection.
AB  - Spinal cord injury (SCI) is a serious clinical problem that causes lifetime
      disabilities to victims and inflicting huge social burden on our society. One of
      the main lacunae in developing potential therapeutic measures in SCI is a lack of
      suitable animal models that could be comparable to clinical situations. Thus,
      development of new animal models of SCI is highly needed to expand our knowledge
      on cell injury and repair process in order to reduce cord pathology, and in
      translating advanced therapies in patients of SCI to improve therapeutic
      strategies. Keeping these views in mind, a suitable animal model is developed in
      our laboratory that can be used to explore new therapeutic tools in SCI. The
      details of our methods used to induce SCI in rodents and neuroprotection achieved
      by use of selected neurotrophic factors are described in this chapter.

PMID- 22367829
TI  - Cogan syndrome: an analysis of reported neurological manifestations.
AB  - BACKGROUND: Patients with Cogan syndrome typically present with nonsyphilitic
      interstitial keratitis and acute onset of sensorineural hearing loss.
      Neurological manifestations have been reported, but various frequencies and
      mechanisms have been proposed. REVIEW SUMMARY: We critically reviewed the English
      literature of Cogan syndrome to determine the nature, frequency, and most likely
      mechanisms of its neurological manifestations. CONCLUSIONS: On the basis of our
      review, we believe that Cogan syndrome can be associated with neurological
      manifestations. Our conclusion is based on reported tissue evidence of vasculitis
      involving the dura, brain, optic nerve, cochleovestibular nerve, and muscle, in
      patients with referable symptoms. However, we believe that the frequency of
      neurological manifestations may have been over reported due to lack of
      confirmatory testing in many of these cases.

PMID- 22367830
TI  - HIV-associated neurocognitive disorders: a historical review.
AB  - BACKGROUND: The central nervous system represents a major target of the human
      immunodeficiency virus (HIV), and the neurocognitive impairments associated with
      the disease represent a major cause of disability. REVIEW SUMMARY: The HIV
      associated neurocognitive disorders are presented from a historical point of
      view. The evolution of our knowledge and understanding of these primary
      complications of HIV infection is reviewed, starting with nomenclature and
      clinical staging and continuing with therapeutic options. CONCLUSIONS: Although
      considerable progress has been made in the research of HIV-associated
      neurocognitive disorders, they continue to represent a clinical challenge for
      neurologists. Because the evolution and the clinical manifestations of HIV
      infection have changed with the introduction of antiretroviral therapy and the
      life expectancy has increased, the problems in these patients are complex and
      need neurologists with a thorough knowledge in HIV infection.

PMID- 22367832
TI  - Bilateral femoral neuropathy after massive toxic ingestion in a suicide attempt.
AB  - INTRODUCTION: Bilateral femoral nerve injury can occur after various surgical and
      nonsurgical processes, but has rarely been reported. CASE REPORT: We describe a
      case of bilateral femoral neuropathy after a suicide attempt in a 41-year-old
      woman. We suggest a stretch mechanism to explain this observation. We also
      discuss the other causes of bilateral nerve palsy, usually secondary to a
      compressive injury, with a review of the medical literature. CONCLUSIONS: The
      patient reported is the first in the literature to have suffered from bilateral
      femoral nerve palsy after a suicide attempt. Half of the reported cases are
      secondary to a surgical process (particularly abdominopelvic surgery). If a
      compressive origin is most frequent, a stretch mechanism may at times explain a
      bilateral femoral neuropathy.

PMID- 22367831
TI  - Combined antithrombotic treatment with aspirin and clopidogrel for patients with
      capsular warning syndrome: a case report.
AB  - Capsular warning syndrome is characterized by recurrent transient ischemic
      attacks and is caused by microthrombosis or hypoperfusion of small-sized vessels.
      The pathophysiological basis of this syndrome is not well understood and
      currently a consensus has not been reached on its optimal treatment. In this
      study, we present 2 cases with favorable clinical outcomes after combined
      antithrombotic treatment with loading doses of clopidogrel and aspirin.

PMID- 22367833
TI  - Poststroke detrusor hyporeflexia in a patient with left medial pontine
      infarction.
AB  - BACKGROUND: Although prognostically and socially significant for both patients
      and their caregivers, poststroke urinary incontinence (PSUI) is often easily
      overlooked or is not well studied because of its clinical variety in humans.
      REVIEW SUMMARY: A 45-year-old woman with poorly controlled hypertension presented
      with acute right-sided hemiparesis and dysarthria. Acute urinary retention was
      diagnosed 2 days after stroke onset, along with the clinical evolution (The
      National Institutes of Health Stroke Scale from 1 to 7; Medical Research Council
      scale from 4 to 2). Brain magnetic resonance imaging showed an acute left medial
      pontine infarction, whereas urodynamic study showed detrusor hyporeflexia 5 days
      after the stroke. PSUI started to improve along with urodynamic studies 10 days
      later and the Foley catheter was removed subsequently. CONCLUSIONS: Left medial
      pontine infarct causes detrusor hyporeflexia, which has not, to our knowledge,
      been reported in the literature. More attention should be given to the appearance
      of PSUI because of its prognostic importance and because patients may not
      recognize their neurogenic bladder symptoms during the acute cerebral shock
      phase.

PMID- 22367835
TI  - An acute tiny left putamenal lesion presenting with transient global amnesia.
AB  - INTRODUCTION: Transient global amnesia (TGA) is one of the most striking
      syndromes in clinical neurology. Brain lesions producing TGA have been reported
      in the hippocampus, amygdala, thalamus, caudate nucleus, and neocortex. CASE
      REPORT: We report a 63-year-old woman presenting with TGA associated with a
      localized lesion in the left putamen. CONCLUSIONS: This case suggests a potential
      role of the putamen in human memory processing.

PMID- 22367834
TI  - Anti-aquaporin-4 antibody-positive definite neuromyelitis optica in a patient
      with thymectomy for myasthenia gravis.
AB  - BACKGROUND: Since serum anti-aquaporin-4 (AQP4) antibody/neuromyelitis optica
      (NMO)-IgG has been detected as a specific biomarker for NMO), new diagnostic
      criteria have been proposed. Recently, a rare coexistence of NMO and myasthenia
      gravis (MG) has been documented. Here, we provide further evidence of the
      association of these 2 immunologic disorders and review the literature. CASE
      REPORT: A 60-year-old woman, who had a history of optic neuritis at age 43,
      developed longitudinally extended transverse myelitis (LETM). She had repeated
      optic neuritis and longitudinally extended transverse myelitis attacks, which
      have been treated by corticosteroid pulse therapy. She was diagnosed as having
      definite NMO, because serum anti-aquaporin-4 antibody was positive. She had also
      been suffering from generalized MG since age 30 and underwent thymectomy at age
      40. There have been 14 patients with NMO associated with MG, most of whom
      developed NMO years after thymectomy. Our patient is the seventh patient with
      seropositive NMO who underwent thymectomy for MG. CONCLUSIONS: The coexistence of
      MG with thymectomy and seropositive NMO suggests an etiopathogenic link between
      these 2 disorders but remains underrecognized by neurologists. Neurologists
      should consider this possible association when encountering atypical
      presentations of either MG or NMO.

PMID- 22367836
TI  - Autoimmune polyendocrine syndrome-3 in a patient with late-onset multiple
      sclerosis.
AB  - We present here the rare case of a 73-year-old patient with very late-onset
      multiple sclerosis who developed autoimmune polyendocrine syndrome (APS)-3.
      Despite only a few reports describing the association between multiple sclerosis
      and APS, both of these diseases have been shown to be associated with HLA-DR4.
      Intriguingly, the HLA genotype profile of this patient included HLA-DR4 which,
      fine mapped to the DRB1*0405-DQA1*0303-DQB1*0401 extended haplotype, reported to
      be a susceptibility haplotype for APS-3 in Japan. This unique genetic background
      might explain the clinical picture of this patient.

PMID- 22367837
TI  - Progressive multifocal leukoencephalopathy in a patient treated with etanercept.
AB  - INTRODUCTION: Recently, increased attention has been paid to the association of
      progressive multifocal leukoencephalopathy (PML) with the use of immunomodulatory
      medications for autoimmune diseases. CASE REPORT: A 23-year-old Native American
      woman with a history of systemic lupus erythematosus and erosive polyarthritis
      treated with prednisone and etanercept presented with focal weakness, hemiataxia,
      diplopia, and dysarthria. Brain magnetic resonance imaging demonstrated
      progressive, T2 signal hyperintensities within the brainstem and cerebellar white
      matter without mass effect or gadolinium enhancement. Cerebrospinal fluid showed
      elevated protein and JC virus polymerase chain reaction positive with 28,600
      copies/ml diagnostic of PML. CONCLUSIONS: The development of PML in this patient
      treated with etanercept and prednisone highlights the increased risk for
      opportunistic infection with JC virus in patients with autoimmune diseases on
      immunosuppressive therapies.

PMID- 22367838
TI  - Glutamic acid decarboxylase autoantibody syndrome presenting as schizophrenia.
AB  - INTRODUCTION: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme
      converting glutamate into gamma-aminobutyric acid. Impaired GAD function can
      alter motor, cognitive, and behavioral function. Anti-GAD antibodies (GADAbs) can
      cause several neurological disorders. However, the association between anti
      GADAbs and pure psychosis, without seizures or focal neurological deficits, is
      not well defined. CASE REPORT: A 19-year-old woman with recent-onset psychotic
      disorder was diagnosed with schizophrenia. Brain magnetic resonance imaging and
      cerebrospinal fluid analysis were normal. Serum anti-GADAb titers were elevated.
      Brain biopsy showed subcortical gliosis and microglia-macrophage infiltration.
      The clinical syndrome improved with immune therapy. CONCLUSIONS: Severe psychosis
      and mild cognitive decline without other neurological features, meeting the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision
      diagnostic criteria for schizophrenia, can result from brain inflammation
      associated with elevated serum anti-GADAbs.

PMID- 22367839
TI  - Amyotrophic lateral sclerosis and frontotemporal lobar degeneration in
      association with CADASIL.
AB  - Amyotrophic lateral sclerosis (ALS) can present with heterogeneous symptoms
      resulting from the involvement of multiple brain systems including extramotor
      cortical areas. Involvement of other brain areas can cause diverse clinical
      symptoms including cognitive impairment and extrapyramidal symptoms. We report
      the case of a 50-year-old woman with bulbar onset ALS and frontotemporal lobar
      degeneration (FTLD), confirmed as cerebral autosomal-dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL). The patient and her first
      degree relatives harbored a mutation (R75P) in the NOTCH3 gene, indicative of
      vascular deficits. The details of this case add plausibility to the idea that
      ALS, FTLD, and CADASIL are different aspects of a spectrum of disorders with
      overlapping pathologic mechanisms.

PMID- 22367840
TI  - Writing from the wards: advice for residents.
AB  - INTRODUCTION: Published articles share information and ideas across fields and
      can be a part of educational and career development. Academic and personal
      interests are the typical motivators, but many residents have trouble with the
      logistics of writing and the simple act of getting started. OBJECTIVE: The
      following article gives concrete advice, structural recommendations and addresses
      logistical concerns in writing manuscripts, focusing on case reports. METHODS:
      The process of writing a paper results in self-teaching, while striving to teach
      others. Working on case reports often produces posters and presentations on the
      way to writing the manuscript. This article reviews different types of case
      reports: from the classic sentinel case, to case series, and video submissions,
      to teaching cases. A "how to" strategy is presented in the writing process, from
      idea, to data, to writing itself. Aspects such as choosing your audience and
      journal are discussed, as well as employing coauthors and working together to
      produce a polished manuscript. CONCLUSIONS: Residents and fellows are immersed in
      clinical medicine but may not possess experience in writing journal articles.
      Presented is advice on and logistics of writing manuscripts that are based on
      clinical data and clinical experience. Through utilizing a structured approach
      and understanding the practicalities involved, more physicians in training can
      write from the wards.

PMID- 22367841
TI  - Safety of thrombolysis in patients over the age of 80.
AB  - BACKGROUND: The safety of intravenous thrombolysis (IVT) in patients with acute
      ischemic stroke over the age of 80 is unclear. We hypothesized that patients over
      the age of 80 can be safely treated with IVT. METHODS: Admission and discharge
      data were collected on all patients at a single tertiary care center presenting
      within 12 hours of onset. Collected data included treatment with IVT,
      demographics, pretreatment National Institutes of Health Stroke Scale score,
      length of stay, mortality, and discharge disposition. Analyses were restricted to
      patients over the age of 80, and the primary outcome was in-hospital mortality.
      Logistic regression was used to examine whether IVT was associated with
      mortality. RESULTS: Between January 1, 2005 and May 30, 2010, 112 patients over
      the age of 80 presented within 3 hours of ischemic stroke onset, and 31 received
      IVT. There were 15 deaths. In multivariable models adjusted for age, sex, race
      ethnicity, and National Institutes of Health Stroke Scale, treatment with IVT,
      compared with no treatment, was not associated with in-hospital death (adjusted
      odds ratio, 1.2; 95% confidence interval, 0.3-4.3). CONCLUSIONS: Treating
      ischemic stroke patients over 80 years with IVT was not associated with an
      increase in mortality in an urban tertiary care center.

PMID- 22367842
TI  - Is dabigatran cost effective compared with warfarin for stroke prevention in
      atrial fibrillation? A critically appraised topic.
AB  - BACKGROUND: Warfarin has provided protection against cardioembolic stroke in the
      setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years.
      Dabigatran, the first oral direct thrombin inhibitor to be approved in the United
      States, promises to provide the same or better stroke protection with reduced
      risk of intracranial hemorrhage. However, it remains to be seen whether grand
      scale adoption of dabigatran will be cost effective. OBJECTIVE: To critically
      assess current evidence regarding the cost effectiveness of dabigatran for
      preventing stroke in patients with NVAF compared with warfarin. METHODS: The
      objective was addressed through the development of a critically appraised topic
      that included a clinical scenario, structured question, literature search
      strategy, critical appraisal, assessment of results, evidence summary,
      commentary, and bottom-line conclusions. Participants included consultant and
      resident neurologists, a medical librarian, clinical epidemiologists, and content
      experts in the field of vascular neurology. RESULTS: A cost-effectiveness
      analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of
      age or older and CHADS2>=1 over their lifetime comparing dabigatran with adjusted
      dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000
      per quality-adjusted life year (QALY), base case results favored high-dose (150
      mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity
      analysis asserted that the cost effectiveness of dabigatran improved if it could
      be obtained for <=$13/d or if it was used in populations with high risk of stroke
      or intracranial hemorrhage. CONCLUSIONS: Dabigatran 150 mg bid ($12,286 per QALY)
      is a cost-effective alternative to International Normalized Ratio-adjusted
      warfarin for the prevention of ischemic stroke in patients 65 years of age or
      older with NVAF.

PMID- 22367843
TI  - Optimal size of craniectomy.

PMID- 22367844
TI  - The area of the bone flap.

PMID- 22367845
TI  - Genetic analysis for predictive screening in hypertrophic cardiomyopathy.

PMID- 22367847
TI  - Personality changes in bulimia nervosa after a cognitive behaviour therapy.
AB  - OBJECTIVES: The goals of this study were to evaluate changes in personality
      traits in outpatients with bulimia nervosa and specific clinical predictors of
      such personality changes, after cognitive behaviour therapy (CBT). METHOD: The
      sample comprised 100 purging bulimia nervosa outpatients (DSM-IV-TR). Assessment
      measures included the Eating Disorders Inventory-2, Symptom Check List Revised
      and Temperament and Character Inventory-Revised, as well as other clinical and
      psychopathological indices. All measures were administered before and after 22
      weeks of group CBT. RESULTS: The temperament traits of Harm Avoidance and Reward
      Dependence and the character traits of Self-Directedness and Self-Transcendence
      changed after CBT. Pre-post CBT reduction in Eating Disorders Inventory-2 total
      score predicted the decrease and increase in Harm Avoidance and Self
      Directedness, respectively. CONCLUSIONS: Results suggest that group CBT in
      outpatient women settings influence changes in some personality traits, which
      appear mainly related to an overall improvement in eating pathology.

PMID- 22367846
TI  - Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS
      binding to mismatched bases in DNA.
AB  - Mismatch repair (MMR) corrects replication errors such as mismatched bases and
      loops in DNA. The evolutionarily conserved dimeric MMR protein MutS recognizes
      mismatches by stacking a phenylalanine of one subunit against one base of the
      mismatched pair. In all crystal structures of G:T mismatch-bound MutS,
      phenylalanine is stacked against thymine. To explore whether these structures
      reflect directional mismatch recognition by MutS, we monitored the orientation of
      Escherichia coli MutS binding to mismatches by FRET and anisotropy with steady
      state, pre-steady state and single-molecule multiparameter fluorescence
      measurements in a solution. The results confirm that specifically bound MutS
      bends DNA at the mismatch. We found additional MutS-mismatch complexes with
      distinct conformations that may have functional relevance in MMR. The analysis of
      individual binding events reveal significant bias in MutS orientation on
      asymmetric mismatches (G:T versus T:G, A:C versus C:A), but not on symmetric
      mismatches (G:G). When MutS is blocked from binding a mismatch in the preferred
      orientation by positioning asymmetric mismatches near the ends of linear DNA
      substrates, its ability to authorize subsequent steps of MMR, such as MutH
      endonuclease activation, is almost abolished. These findings shed light on
      prerequisites for MutS interactions with other MMR proteins for repairing the
      appropriate DNA strand.

PMID- 22367848
TI  - 1H NMR spectroscopic identification of protonable sites in cryptolepines with C
      11 substituents containing two amino functionalities.
AB  - Knowledge of protonable sites and acid dissociation constants of cryptolepine
      derivatives having C-11 substituents containing two amino functionalities is of
      great importance to the understanding of the mechanism of their antimalarial
      action, which may contribute to their further development as drug candidates. In
      this work, we applied (1)H NMR titration to investigate the acid-base
      characteristics of these polyprotic compounds in the pH range 3-13. We identified
      three acid-base equilibria with most acid dissociation constants (pK(a)*) being
      greater than 10.5, which prevented us from using the potentiometric method.
      Overall, (1)H NMR titration was sensitive and suitable for the determination of
      pK(a) values for these drug leads.

PMID- 22367849
TI  - Targeting ErbB-1 and ErbB-4 in irradiated head and neck cancer: results of in
      vitro and in vivo studies.
AB  - BACKGROUND: ErbB oncogenes have a major role in cancer. The role of ErbB-4 in
      cancer cell biology and the effect of anti-ErbB-1 and anti-ErbB-4 monoclonal
      antibodies were evaluated in this study. METHODS: ErbB-4 expression and binding
      was evaluated by Western blot, enzyme-linked immunosorbent assay (ELISA),
      fluorescent microscopy, and flow cytometry. Cell survival was measured by XTT
      assay. Tumor progression was followed up in nude mice model. RESULTS: High ErbB-1
      levels in head and neck cancer cell lines were determined, whereas ErbB-4
      expression varied. Specific antibody binding to the cells was demonstrated. High
      ErbB-4 expressing squamous cell carcinoma 1 (SCC-1) cells proliferated faster and
      generated faster growing tumors in mice. Cetuximab and mAb-3 reduced cell
      survival proportional to ErbB-1 and ErbB-4 expression. Combination of antibodies
      with irradiation was most effective in reducing cell survival and tumor growth.
      CONCLUSION: ErbB-4 plays a role in head and neck cancer cell biology. Anti-ErbB-4
      targeted therapy can serve as a new strategy against head and neck cancer when
      combined with established treatments.

PMID- 22367850
TI  - Systematic review and meta-analysis of cutting diathermy versus scalpel for skin
      incision.
AB  - BACKGROUND: Skin incisions have traditionally been made using a scalpel. Cutting
      diathermy, a more recent alternative, is thought to increase the risk of
      infection, impair healing and decrease cosmesis. Recent studies suggest
      otherwise, claiming that diathermy may offer potential advantages with respect to
      blood loss, incision time and postoperative pain. The aim of this meta-analysis
      was to compare skin incisions made by either scalpel or cutting diathermy.
      METHODS: A systematic literature search and review was performed for studies
      published from January 1980 until June 2011. Randomized clinical trials comparing
      scalpel and cutting diathermy for skin incisions of any operation were included.
      Primary outcomes included wound complication rate, blood loss, incision times and
      pain scores. RESULTS: Fourteen randomized trials met the criteria for inclusion
      in the meta-analysis, providing outcome data for a total of 2541 patients (1267
      undergoing skin incision by cutting diathermy and 1274 by scalpel). The median
      length of follow-up across all studies was 6 weeks (range 4 days to 19 months).
      Compared with a scalpel incision, cutting diathermy resulted in significantly
      less blood loss (mean difference 0.72 ml/cm(2); P < 0.001) and shorter incision
      times (mean difference 36 s; P < 0.001), with no differences in the wound
      complication rate (odds ratio 0.87; P = 0.29) or pain score at 24 h (mean
      difference 0.89; P = 0.05). CONCLUSION: Skin incisions made by cutting diathermy
      are quicker and associated with less blood loss than those made by scalpel, and
      there are no differences in the rate of wound complications or postoperative
      pain.

PMID- 22367851
TI  - In-treatment 4D cone-beam CT with image-based respiratory phase recognition.
AB  - The use of respiration-correlated cone-beam computed tomography (4D-CBCT) appears
      to be crucial for implementing precise radiation therapy of lung cancer patients.
      The reconstruction of 4D-CBCT images requires a respiratory phase. In this paper,
      we propose a novel method based on an image-based phase recognition technique
      using normalized cross correlation (NCC). We constructed the respiratory phase by
      searching for a region in an adjacent projection that achieves the maximum
      correlation with a region in a reference projection along the cranio-caudal
      direction. The data on 12 lung cancer patients acquired just prior to treatment
      and on 3 lung cancer patients acquired during volumetric modulated arc therapy
      treatment were analyzed in the search for the effective area of cone-beam
      projection images for performing NCC with 12 combinations of registration area
      and segment size. The evaluation was done by a "recognition rate" defined as the
      ratio of the number of peak inhales detected with our method to that detected by
      eye (manual tracking). The average recognition rate of peak inhale with the most
      efficient area in the present method was 96.4%. The present method was feasible
      even when the diaphragm was outside the field of view. With the most efficient
      area, we reconstructed in-treatment 4D-CBCT by dividing the breathing signal into
      four phase bins; peak exhale, peak inhale, and two intermediate phases. With in
      treatment 4D-CBCT images, it was possible to identify the tumor position and the
      tumor size in moments of inspiration and expiration, in contrast to in-treatment
      CBCT reconstructed with all projections.

PMID- 22367852
TI  - Incidence of thromboembolic complications in patients with atrial fibrillation or
      mechanical heart valves with a subtherapeutic international normalized ratio: a
      prospective multicenter cohort study.
AB  - Subtherapeutic international normalized ratio (INR) is frequently encountered in
      clinical practice, and patients with high-risk atrial fibrillation (AF) and with
      mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an
      increased risk of thromboembolic events (TE). However, there are no prospective
      data evaluating this risk. Consecutive patients with a history of stable
      anticoagulation, but with a subtherapeutic INR, were prospectively included. Data
      on use and dose of low-molecular weight heparin (LMWH) bridging therapy were
      collected. The incidence of objectively confirmed TE and of major bleeding events
      within 90 days after the index INR was assessed. Five hundred and one patients
      with INR value 0.5-1 INR units below the lower limit of the patient-specific
      target INR were included in the study (280 with MHV and 221 with AF and CHADS2
      score >=3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven
      patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for
      100 patients year). All the events occurred within 14 days after the index INR.
      When we consider only patients who did not receive bridging therapy, the
      incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49,
      2.64%; 4.58 events for 100 patients year). There were no major bleeding events.
      The risk of TE in this population was not negligible. Given the frequent
      observation of subtherapeutic INR levels when monitoring vitamin K antagonists,
      this finding warrants additional investigation to improve the management of these
      patients.

PMID- 22367853
TI  - Cervical cytology screening programs: similarities and differences between the
      United States and United Kingdom systems.

PMID- 22367854
TI  - Supramolecular tandem enzyme assays.
AB  - We conceptualize a novel approach towards enzyme assays based on the reversible
      and competitive binding of a fluorescent dye and the substrate as well as product
      of an enzymatic reaction to a macrocyclic host. This method was termed
      "supramolecular tandem assay", and has been applied to inhibitor and activator
      screening, sensor array development, and enantiomeric excess determination of
      amino acids. The simple and rapid read-out by fluorescence allows their
      straightforward implementation into high-throughput screening.

PMID- 22367855
TI  - Rab3D regulates amylase levels, not agonist-induced amylase release, in AR42J
      cells.
AB  - Rab3D is a low molecular weight GTP-binding protein that associates with
      secretory granules in exocrine cells. AR42J cells are derived from rat pancreatic
      exocrine tumor cells and develop an acinar cell-like phenotype when treated with
      dexamethasone (Dex). In the present study, we examined the role of Rab3D in Dex
      treated AR42J cells. Rab3D expression and localization were analyzed by
      subcellular fractionation and immunoblotting. The role of Rab3D was examined by
      overexpressing myc-labeled wild-type-Rab3D and a constitutively active form of
      Rab3D (Rab3D-Q81L) in AR42J cells. We found that Rab3D is predominantly membrane
      associated in AR42J cells and co-localizes with zymogen granules (ZG). Following
      CCK-8-induced exocytosis, amylase-positive ZGs appeared to move towards the
      periphery of the cell and co-localization between Rab3D and amylase was less
      complete when compared to basal conditions. Overexpression of WT, but not mutant
      Rab3D, resulted in an increase in cellular amylase levels. Overexpression of
      mutant and WT Rab3D did not affect granule morphology, CCK-8-induced secretion,
      long-term (48 hr) basal amylase release or granule density. We conclude that
      Rab3D is not involved in agonist-induced exocytosis in AR42J cells. Instead,
      Rab3D may regulate amylase content in these cells.

PMID- 22367856
TI  - Autophagy favors Brucella melitensis survival in infected macrophages.
AB  - This study investigated the role of autophagy in the survival of the invasive
      bacterium Brucella melitensis strain 16M in murine macrophages. Here, Brucella
      melitensis 16M was found to trigger autophagosome formation, enhance autophagy
      flux and increase the expression level of the autophagy marker protein LC3-II.
      When autophagy was pharmacologically inhibited by 3-methyladenine (3-MA),
      Brucella replication efficiency was significantly decreased (p < 0.05). These
      results suggest that autophagy favors Brucella melitensis 16M survival in murine
      macrophages.

PMID- 22367857
TI  - Positron emission tomography oncology research in the UK:  a comparison with USA
      and Europe.
AB  - PET imaging with 18F-fluorodeoxyglucose (FDG) has become a valuable procedure in
      oncology patient management and drug development. The availability of non-FDG
      radiotracers to study different aspects of cancer biology presents new
      opportunities to improve healthcare outcomes and develop new therapeutics. An
      investigation has been carried out to determine the extent of the use of non-FDG
      tracers in the UK, assess overall oncology PET research activity and document
      current UK PET infrastructure. There has been significant recent investment in
      PET facilities, increasing the UK's capacity to undertake PET research.
      Nevertheless, the UK still has a lower level of PET equipment compared with
      Europe and the USA. Despite the increase in PET imaging capacity in UK research
      centres, there has not been an increase in non-FDG research, with most studies
      utilizing FDG at multiple sites. Most non-FDG trials are single-centre studies at
      well established centres. High tracer prices, a limited range of non-FDG tracers
      and restricted geographical availability make multicentre trials with non-FDG
      radiotracers difficult. Several solutions have been identified: formation of
      purchasing consortia for 18F-labelled radiotracers, production of radiotracers
      with longer half-lives and establishment of production at regional supply
      centres.

PMID- 22367858
TI  - Computer-aided quantitative bone scan assessment of prostate cancer treatment
      response.
AB  - OBJECTIVE: The development and evaluation of a computer-aided bone scan analysis
      technique to quantify changes in tumor burden and assess treatment effects in
      prostate cancer clinical trials. METHODS: We have developed and report on a
      commercial fully automated computer-aided detection (CAD) system. Using this
      system, scan images were intensity normalized, and then lesions were identified
      and segmented by anatomic region-specific intensity thresholding. Detected
      lesions were compared against expert markings to assess the accuracy of the CAD
      system. The metrics Bone Scan Lesion Area, Bone Scan Lesion Intensity, and Bone
      Scan Lesion Count were calculated from identified lesions, and their utility in
      assessing treatment effects was evaluated by analyzing before and after scans
      from metastatic castration-resistant prostate cancer patients: 10 treated and 10
      untreated. In this study, patients were treated with cabozantinib, a MET/vascular
      endothelial growth factor inhibitor resulting in high rates of resolution of bone
      scan abnormalities. RESULTS: Our automated CAD system identified bone lesion
      pixels with 94% sensitivity, 89% specificity, and 89% accuracy. Significant
      differences in changes from baseline were found between treated and untreated
      groups in all assessed measurements derived by our system. The most significant
      measure, Bone Scan Lesion Area, showed a median (interquartile range) change from
      baseline at week 6 of 7.13% (27.61) in the untreated group compared with -73.76%
      (45.38) in the cabozantinib-treated group (P=0.0003). CONCLUSION: Our system
      accurately and objectively identified and quantified metastases in bone scans,
      allowing for interpatient and intrapatient comparison. It demonstrates potential
      as an objective measurement of treatment effects, laying the foundation for
      validation against other clinically relevant outcome measures.

PMID- 22367859
TI  - The role of 18F-FDG PET/CT in detecting colorectal cancer recurrence in patients
      with elevated CEA levels.
AB  - INTRODUCTION: In this study we aimed to define the success of fluorine-18 (18F)
      fluorodeoxyglucose (FDG) PET/computed tomography (PET/CT) in detecting recurrent
      disease in our patient group with colorectal cancer (CRC) and elevated
      carcinoembryonic antigen (CEA) levels. MATERIAL AND METHOD: Patients who had a
      previous diagnosis of CRC were searched retrospectively in our PET center
      database. Seventy-six 18F-FDG PET/CT studies between October 2006 and December
      2010 of 69 patients (25 women, 44 men; mean age: 61.61 +/- 4.1 years) with
      elevated CEA levels were evaluated. 18F-FDG PET/CT findings and concurrent
      abdominopelvic contrast-enhanced computed tomography (ceCT) findings were
      compared with histopathological findings and/or clinical follow-up data as the
      'gold standard'. RESULTS: In the patient-based analysis, the sensitivity and
      specificity of 18F-FDG PET/CT in the detection of disease recurrence were
      calculated as 97 and 61%, respectively. A statistically significant difference
      was found in frequencies of positive and negative 18F-FDG PET/CT findings between
      patients with or without recurrent disease by gold standard (P<0.05). There was
      no correlation between patients' serum CEA levels and lesions' maximum
      standardized uptake values (P=0.85). The sensitivity and specificity of ceCT were
      computed as 51 and 60%, respectively. In the evaluation of separate patient
      groups, although the sensitivity and specificity of 18F-FDG PET/CT were
      calculated as 100 and 60% in the group whose CEA level elevation was less than
      two-fold (5-9.9 ng/ml), these were 100 and 75% in the group with CEA elevation
      less than three-fold (10-14.9 ng/ml) and 95 and 62% in the group with elevation
      more than three-fold (>= 15 ng/ml). The sensitivity and specificity of 18F-FDG
      PET/CT were computed as 98 and 85% in the lesion-based evaluation. The
      sensitivity and specificity of ceCT were 73 and 86%, respectively. CONCLUSION:
      18F-FDG PET/CT is a safe imaging method that can be used in the determination of
      CRC recurrence in patients with elevated CEA levels, regardless of the CEA level.

PMID- 22367860
TI  - Re: Is normalized residual activity a good marker of renal output efficiency?

PMID- 22367862
TI  - Adapted group-based dialectical behaviour therapy for binge eating in a
      practicing clinic: clinical outcomes and attrition.
AB  - Research evidence has been accumulating for the efficacy of dialectical behaviour
      therapy (DBT) for binge eating. However, support for its effectiveness and
      transportability beyond efficacy trials is lacking. The current study evaluated
      the feasibility of group-based DBT for binge eating within the context of an
      operating community clinic. Women ages 24-49 (M = 39.60, SD = 9.53) with either
      subthreshold and full-threshold binge eating disorder or bulimia nervosa formed
      the group and comprised the sample (n = 5 treatment completers). Positive
      outcomes included significant improvement in both binge eating and secondary
      outcomes with the Eating Disorder Inventory subscales of Bulimia,
      Ineffectiveness, Perfectionism and Interpersonal Distrust. Attrition was elevated
      compared with previous efficacy trials, suggesting the need for increased
      attention to how to improve retention within routine practice settings. Given our
      limited sample size, these findings are viewed as promising but preliminary.

PMID- 22367863
TI  - Transposable elements as tools for reshaping the genome: it is a huge world after
      all!
AB  - Transposable elements (TEs) are discrete pieces of DNA that can move from one
      site to another within genomes and sometime between genomes. They are found in
      all major branches of life. Because of their wide distribution and considerable
      diversity, they are a considerable source of genomic variation and as such, they
      constitute powerful drivers of genome evolution. Moreover, it is becoming clear
      that the epigenetic regulation of certain genes is derived from defense
      mechanisms against the activity of ancestral transposable elements. TEs now tend
      to be viewed as natural molecular tools that can reshape the genome, which
      challenges the idea that TEs are natural tools used to answer biological
      questions. In the first part of this chapter, we review the classification and
      distribution of TEs, and look at how they have contributed to the structural and
      transcriptional reshaping of genomes. In the second part, we describe
      methodological innovations that have modified their contribution as molecular
      tools.

PMID- 22367864
TI  - Using and understanding RepeatMasker.
AB  - RepeatMasker is a program that screens DNA sequences for interspersed repeats and
      low-complexity DNA sequences. In this chapter, we present the procedure to
      routinely use this program on a personal computer.

PMID- 22367865
TI  - Roadmap for annotating transposable elements in eukaryote genomes.
AB  - Current high-throughput techniques have made it feasible to sequence even the
      genomes of non-model organisms. However, the annotation process now represents a
      bottleneck to genome analysis, especially when dealing with transposable elements
      (TE). Combined approaches, using both de novo and knowledge-based methods to
      detect TEs, are likely to produce reasonably comprehensive and sensitive results.
      This chapter provides a roadmap for researchers involved in genome projects to
      address this issue. At each step of the TE annotation process, from the
      identification of TE families to the annotation of TE copies, we outline the
      tools and good practices to be used.

PMID- 22367866
TI  - To detect and analyze sequence repeats whatever be their origin.
AB  - The development of numerous programs for the identification of mobile elements
      raises the issue of the founding concepts that are shared in their design. This
      is necessary for at least three reasons. First, the cost of designing,
      developing, debugging, and maintaining software could present a danger of
      distracting biologists from their main bioanalysis tasks that require a lot of
      energy. Some key concepts on exact repeats are always underlying the search for
      genomic repeats and we recall the most important ones. All along the chapter, we
      try to select practical tools that may help the design of new identification
      pipelines. Second, the huge increase of sequence production capacities requires
      to use the most efficient data structures and algorithms to scale up tools in
      front of the data deluge. This paper provides an up-to-date glimpse on the art of
      string indexing and string matching. Third, there exists a growing knowledge on
      the architecture of mobile elements built from literature and the analysis of
      results generated by these pipelines. Besides data management which has led to
      the discovery of new families or new elements of a family, the community has an
      increasing need in knowledge management tools in order to compare, validate, or
      simply keep trace of mobile element models. We end the paper with first
      considerations on what could help the near future of such research on models.

PMID- 22367867
TI  - Exploring bacterial insertion sequences with ISfinder: objectives, uses, and
      future developments.
AB  - We describe here the use of the ISfinder database and its associated software.
      ISfinder was conceived -initially as a comprehensive database for prokaryotic
      insertion sequences (ISs). It now includes software for visualising complete and
      partial IS copies in whole genomes (ISbrowser) and for high-quality genome
      annotation (Insertion Sequence Semi-automatic Genome Annotation).

PMID- 22367868
TI  - Methods and software in NGS for TE analysis.
AB  - The recent development of next-generation sequencing (NGS) technologies allowed
      various authors to imagine, test, and validate new approaches for TE analysis, in
      their nature, type, activity, or quantity. In this chapter, we describe briefly
      the technologies used, then the various approaches and methods used already, and
      finally some potential new methods. In contrast to the more molecular chapters of
      the book, the approaches described here are purely bioinformatics, and have a set
      of NGS data as a starting point. Moreover, as these analyses are quite recent in
      the field, most of them were only performed once, and we cannot be sure that they
      could be reused in other species or context than the original one. However, there
      are a lot of interesting approaches and results that NGS can provide in the TE
      field.

PMID- 22367869
TI  - The application of LTR retrotransposons as molecular markers in plants.
AB  - Retrotransposons are a major agent of genome evolution. Various molecular marker
      systems have been developed that exploit the ubiquitous nature of these genetic
      elements and their property of stable integration into dispersed chromosomal loci
      that are polymorphic within species. The key methods, SSAP, IRAP, REMAP, RBIP,
      and ISBP, all detect the sites at which the retrotransposon DNA, which is
      conserved between families of elements, is integrated into the genome. Marker
      systems exploiting these methods can be easily developed and inexpensively
      deployed in the absence of extensive genome sequence data. They offer access to
      the dynamic and polymorphic, nongenic portion of the genome and thereby
      complement methods, such as gene-derived SNPs, that target primarily the genic
      fraction.

PMID- 22367870
TI  - Individual analysis of transposon polymorphisms by AFLP.
AB  - The DNA polymorphisms caused by insertion and excision of transposable elements
      (TEs) are applicable in studying genome dynamics, genetic diversity, and
      molecular evolution, generating genome-wide molecular maps and investigating
      functional attributes of transposons in epigenetics and diseases. Identification
      of individual mutations caused by TEs using the principles of amplified fragment
      length polymorphism assay is a reliable and cost-effective approach. The method
      relies upon selective polymerase chain reaction (PCR) of flanking regions of TE
      insertion sites in the genome. A detailed procedure is described in this chapter
      that outlines each step starting from the preparation of PCR template to
      identification and isolation of the polymorphic bands. The approach outlined in
      this protocol can be adopted to identify individual polymorphisms caused by any
      transposon in any organism.

PMID- 22367871
TI  - Construction of a library of random mutants in the spirochete Leptospira biflexa
      using a mariner transposon.
AB  - In comparison to other bacterial species, genetics of leptospires are in their
      infancy. Recently, we developed a system for random transposon mutagenesis in the
      saprophyte Leptospira biflexa and then applied this approach to the pathogen L.
      interrogans. Thousands of random mutants can be readily obtained in -L. -biflexa
      by random insertion of Himar1 in the genome, thereby generating extensive
      libraries of mutants that could be screened for phenotypes affecting diverse
      aspects of the biology of the bacterium. This system should be particularly
      useful for the identification of new genes of unknown function in Leptospira spp.
      This chapter describes a procedure for transposition in L. biflexa via
      conjugation of a plasmid delivering Himar1, isolation of mutants, and mapping of
      the insertion sites on the chromosome.

PMID- 22367872
TI  - Ac-Ds solutions for rice insertion mutagenesis.
AB  - Rice is the model plant for monocotyledons. Since the completion of the high
      quality sequence of its genome, the international community is deploying efforts
      to identify the function of the 30-40,000 nontransposable element genes of rice.
      These efforts comprise the creation of large collections of rice mutants
      accessible to the international scientific community. In addition to loss of
      function mutants, insertion mutagenesis using Agrobacterium-mediated
      transformation and engineered mobile elements allows the identification of genes
      through enhancer or gene trapping or activation tagging. The maize transposable
      element Ac-Ds is known to be active in rice since the early 1990s and it does not
      interfere with endogenous rice transposons. This is the guaranty that induced
      mutation obtained with the mobility of the Ds element will be stable when the
      source of Ac transposase is removed from the mutated genome. In this paper, we
      describe single- or double-component T-DNA constructs that have been used to
      introduce a functional Ac-Ds system in rice and allowed the generation and
      selection of different type of Ds insertion mutations in the rice genome.

PMID- 22367873
TI  - Engineering the Caenorhabditis elegans genome by Mos1-induced transgene
      instructed gene conversion.
AB  - Mos1-induced transgene-instructed gene conversion (MosTIC) is a technique of
      choice to engineer the genome of the nematode Caenorhabditis elegans. MosTIC is
      initiated by the excision of Mos1, a DNA transposon of the Tc1/Mariner super
      family that can be mobilized in the germ line of C. elegans. Mos1 excision
      creates a DNA double-strand break that is repaired by several cellular
      mechanisms, including transgene-instructed gene conversion. For MosTIC, the
      transgenic repair template used by the gene conversion machinery is made of
      sequences that share DNA homologies with the genomic region to engineer and
      carries the modifications to be introduced in the genome. In this chapter, we
      present two MosTIC protocols routinely used.

PMID- 22367874
TI  - Genome-wide manipulations of Drosophila melanogaster with transposons, Flp
      recombinase, and PhiC31 integrase.
AB  - Transposable elements, the Flp recombinase, and the PhiC31 integrase are used in
      Drosophila melanogaster for numerous genome-wide manipulations. Often, their use
      is combined in a synergistic fashion to alter and engineer the fruit fly genome.
      Transposons are the foundation for all transgenic technologies in flies and hence
      almost all innovations in the fruit fly. They have been instrumental in the
      generation of genome-wide collections of insertions for gene disruption and
      manipulation. Many important transgenic strains of these collections are
      available from public repositories. The Flp protein is the most widely used
      recombinase to induce mitotic clones to study individual gene function. However,
      Flp has also been used to generate chromosome- and genome-wide collections of
      precise deletions, inversions, and duplications. Similarly, transposons that
      contain attP attachment sites for the PhiC31 integrase can be used for numerous
      applications. This integrase was incorporated into a transgenesis system that
      allows the integration of small to very large DNA fragments that can be easily
      manipulated through recombineering. This system allowed the creation of genomic
      DNA libraries for genome-wide gene manipulations and X chromosome duplications.
      Moreover, the attP sites are being used to create libraries of tens of thousands
      of RNAi constructs and tissue-specific GAL4 lines. This chapter focuses on genome
      wide applications of transposons, Flp recombinase, and PhiC31 integrase that
      greatly facilitate experimental manipulation of Drosophila.

PMID- 22367875
TI  - The Sleeping Beauty transposon toolbox.
AB  - The mobility of class II transposable elements (DNA transposons) can be
      experimentally controlled by separating the two functional components of the
      transposon: the terminal inverted repeat sequences that flank a gene of interest
      to be mobilized and the transposase protein that can be conditionally supplied to
      drive the transposition reaction. Thus, a DNA molecule of interest (e.g., a
      fluorescent marker, an shRNA expression cassette, a mutagenic gene trap or a
      therapeutic gene construct) cloned between the inverted repeat sequences of a
      transposon-based vector can be stably integrated into the genome in a regulated
      and highly efficient manner. Sleeping Beauty (SB) was the first transposon ever
      shown capable of gene transfer in vertebrate cells, and recent results confirm
      that SB supports a full spectrum of genetic engineering in vertebrate species,
      including transgenesis, insertional mutagenesis, and therapeutic somatic gene,
      transfer both ex vivo and in vivo. This methodological paradigm opened up a
      number of avenues for genome manipulations for basic and applied research. This
      review highlights the state-of-the-art in SB transposon technology in diverse
      genetic applications with special emphasis on the transposon as well as
      transposase vectors currently available in the SB transposon toolbox.

PMID- 22367876
TI  - PiggyBac toolbox.
AB  - The PiggyBac (PB) transposon system was originally derived from the cabbage
      looper moth Trichoplusia ni and represents one of the most promising transposon
      systems to date. Engineering of the PB transposase enzyme (PBase) and its cognate
      transposon DNA elements resulted in a substantial increase in transposition
      activities. Consequently, this has greatly enhanced the versatility of the PB
      toolbox. It is now widely used for stable gene delivery into a broad variety of
      cell types from different species, including mammalian cells. This opened up new
      perspectives for potential therapeutic applications in the fields of gene therapy
      and regenerative medicine. In particular, we have recently demonstrated that PB
      transposons could be used to stably deliver genes into human CD34(+)
      hematopoietic stem cells (HSCs) resulting in sustained transgene expression in
      its differentiated progeny. The PB transposon system is particularly attractive
      for the generation of induced pluripotent stem cells (iPS). Typically, this can
      be accomplished by stable gene transfer of genes encoding one or more
      reprogramming factors (i.e., c-MYC, KLF-4, OCT-4, and/or SOX-2). We have
      generated a PB-based nonviral reprogramming toolbox that contains different
      combinations of these reprogramming genes. The main advantage of using this PB
      toolbox for iPS generation is that the reprogramming cassette can be excised by
      de novo transposase expression, without leaving any molecular trace in the target
      cell genome. This "traceless excision" paradigm obviates potential risks
      associated with inadvertent re-expression of reprogramming factors in the iPS
      progeny. These various applications in gene therapy, stem cell engineering, and
      regenerative medicine underscore the emerging versatility of the PB toolbox.

PMID- 22367877
TI  - Insertion site pattern: global approach by linear amplification-mediated PCR and
      mass sequencing.
AB  - In gene therapy, viral or nonviral integrating vectors are used to deliver a
      corrected gene to replace the corresponding defective cellular gene. As vector
      delivery is (yet) commonly not targeted to a specific site in the host genome,
      and vector integration may lead to unwanted cellular gene deregulation, the
      comprehensive analysis of vector locations is a crucial approach to assess vector
      biosafety and to follow the fate of the gene corrected cells in vivo. The
      retrieved vector integration sites are unique for each transduced cell clone,
      thereby serving as a molecular marker and allowing to track distinct cell clones
      in various samples. Today, several PCR-based methods are available for the
      identification and characterization of unknown flanking DNA sequences (Mueller
      and Wold Science 246:780-786, 1989; Paruzynski et al. Nat Protoc 5:1379-1395,
      2010; Schmidt et al. Nat Methods 4:1051-1057, 2007; Silver and Keerikatte J Virol
      63:1924-1928, 1989). Thereof, the linear amplification-mediated PCR (LAM-PCR)
      proved to exhibit the highest sensitivity, allowing the detection of
      miscellaneous vector integration sites in one sample. The broad application
      spectrum and robustness of LAM-PCR has been approved by its application as a tool
      for the molecular follow up of gene-modified cells in preclinical and clinical
      gene therapy trials (Li et al. Science 296:497, 2002; Cartier et al. Science
      326:818-823, 2009; Ott et al. Nat Med 12:401-409, 2006; Deichmann et al. J Clin
      Invest 117:2225-2232, 2007). The combination of LAM-PCR and next-generation
      sequencing (NGS) platforms offers the opportunity to study the clonal inventory
      and pharmacokinetics in clinical gene therapy studies.

PMID- 22367878
TI  - Comprehensive DNA methylation profiling of human repetitive DNA elements using an
      MeDIP-on-RepArray assay.
AB  - Hypomethylation of repetitive DNA elements is a common epigenetics event in
      cancer. Although it is believed that this hypomethylation impacts chromosomal and
      transcriptional stability of the genome, the extent of repetitive sequences
      contribution to the development and progression of human cancers remains to be
      clarified. Repetitive sequences have largely been ignored by genome-wide studies,
      and thus little is known about the DNA methylation profiles of different
      repetitive DNA elements types. As a step toward investigating epigenetic
      landscape of repetitive DNA, we have developed a repeat-specific DNA microarray
      called RepArray. The RepArray comprises 236 prototypic oligonucleotides that span
      the main repetitive elements families found in the human genome. Combined to a
      methylated DNA immunoprecipitation (MeDIP) approach, RepArray allows depicting
      simultaneously the global trends that affect multiple repeat classes through the
      analysis of a restricted number of targets. Here, we present the MeDIP-on
      RepArray protocol as it was established in our laboratory to delineate DNA
      methylation changes after chemical or genetic disruption of DNA methyltransferase
      activity in cells. It might serve as a workflow guideline for screening DNA
      methylation changes on repetitive elements during development and aging, among
      tissues and in various types of stress or pathological situations.

PMID- 22367879
TI  - Novel approach for the development of new antibodies directed against transposase
      derived proteins encoded by human neogenes.
AB  - Molecular domestication of several DNA transposons has occurred during the
      evolution of the primate lineage, and has led to the emergence of at least 42 new
      genes known as neogenes. Because these genes are derived from transposons, they
      encode proteins that are related to certain recombinases, known as transposases.
      Consequently, they may make an important contribution to the genetic instability
      of some human cells. In order to investigate the role of these neogenes, we need
      to be able to study their expression as proteins, for example in tumours, which
      often provide good models of genetic instability. In order to perform such
      studies, polyclonal antibodies directed against the proteins expressed by
      neogenes are obtained using a recently developed new method of Nanospheres/DNA
      immunisation in laboratory mammals. In this chapter, we describe a fully
      integrated process of producing antibodies that consists of a series of steps
      starting with the preparation and synthetic formulation of plasmids encoding
      neogenes, and culminating in the final production and confirmation of the quality
      of these polyclonal antibodies.

PMID- 22367880
TI  - Cdk1, but not Cdk2, is the sole Cdk that is essential and sufficient to drive
      resumption of meiosis in mouse oocytes.
AB  - Mammalian oocytes are arrested at the prophase of meiosis I during fetal or
      postnatal development, and the meiosis is resumed by the preovulatory surge of
      luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases
      (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown.
      Previous studies have shown that deletions of Cdk3, Cdk4 or Cdk6 in mice result
      in viable animals with normal oocyte maturation, indicating that these Cdks are
      not essential for the meiotic maturation of oocytes. In addition, conventional
      knockout of Cdk1 and Cdk2 leads to embryonic lethality and postnatal follicular
      depletion, respectively, making it impossible to study the functions of Cdk1 and
      Cdk2 in oocyte meiosis. In this study, we generated conditional knockout mice
      with oocyte-specific deletions of Cdk1 and Cdk2. We showed that the lack of Cdk1,
      but not of Cdk2, leads to female infertility due to a failure of the resumption
      of meiosis in the oocyte. Re-introduction of Cdk1 mRNA into Cdk1-null oocytes
      largely resumed meiosis. Thus, Cdk1 is the sole Cdk that is essential and
      sufficient to drive resumption of meiosis in mouse oocytes. We also found that
      Cdk1 maintains the phosphorylation status of protein phosphatase 1 and lamin A/C
      in oocytes in order for meiosis resumption to occur.

PMID- 22367881
TI  - Hartmann-Hahn 2D-map to optimize the RAMP-CPMAS NMR experiment for pharmaceutical
      materials.
AB  - Cross polarization-magic angle spinning (CPMAS) is the most used experiment for
      solid-state NMR measurements in the pharmaceutical industry, with the well-known
      variant RAMP-CPMAS its dominant implementation. The experimental work presented
      in this contribution focuses on the entangled effects of the main parameters of
      such an experiment. The shape of the RAMP-CP pulse has been considered as well as
      the contact time duration, and a particular attention also has been devoted to
      the radio-frequency (RF) field inhomogeneity. (13)C CPMAS NMR spectra have been
      recorded with a systematic variation of (13)C and (1)H constant radiofrequency
      field pair values and represented as a Hartmann-Hahn matching two-dimensional
      map. Such a map yields a rational overview of the intricate optimal conditions
      necessary to achieve an efficient CP magnetization transfer. The map also
      highlights the effects of sweeping the RF by the RAMP-CP pulse on the number of
      Hartmann-Hahn matches crossed and how RF field inhomogeneity helps in increasing
      the CP efficiency by using a larger fraction of the sample. In the light of the
      results, strategies for optimal RAMP-CPMAS measurements are suggested, which lead
      to a much higher efficiency than constant amplitude CP experiment.

PMID- 22367882
TI  - Objective and subjective changes in voice quality after radiotherapy for early
      (T1 or T2, N0) laryngeal cancer: a pilot prospective cohort study.
AB  - BACKGROUND: Limited data exist on long-term voice quality after treatment for
      early laryngeal cancer. We report on the feasibility of establishing a dedicated
      service to assess changes after radiotherapy. METHODS: From June 1999 to December
      2005, all patients referred for radical radiotherapy for early laryngeal cancers
      were invited to join a prospective cohort study. Subjective and objective voice
      quality tests were performed before and after treatment and at 3, 6, 12, and 24
      months after treatment. RESULTS: Twenty-seven patients were screened for the
      study. Sufficient data were available for 15 (56%) patients. Both subjective and
      objective assessments improved significantly. CONCLUSIONS: This pilot study shows
      that it is possible to collect prospective voice quality data. There are both
      subjective and objective improvements in voice that persist to at least 2 years
      after radiotherapy. We propose the use of the methods described here to study
      voice outcomes in a lager cohort of patients treated with both surgery and
      radiotherapy.

PMID- 22367883
TI  - Cervical screening in England: the past, present, and future.
AB  - Cervical screening in England commenced in a disorganized fashion in 1964. The
      flaws of this approach became apparent in the mid-1980s and led to the inception
      of the National Health Service Cervical Screening Programme (NHSCSP). The main
      features of this program are its population-based registry, accessibility to all
      women within the screening age range, its systematic process of call and recall,
      national coordination, and quality assurance. Its success is in part based on its
      ability to evolve as evidence necessitates, and throughout the period of 2000
      2010, it embarked upon a series of developments involving liquid-based cytology,
      which also provided the means to conduct reflex high-risk human papillomavirus
      (HR-HPV) testing and the potential to automate the screening process. As a result
      of evidence acquired since 2000, the NHSCSP is currently based on a system of
      primary cytology with HPV triage for low-grade abnormalities combined with
      cytology plus a HR-HPV "test of cure" for women who have received treatment for
      cervical intraepithelial neoplasia. Future challenges for the program will
      involve finding solutions to increasing screening uptake among women <30 years of
      age-a problem that may be exacerbated when vaccinated women reach the screening
      age, while making plans to accommodate HPV primary screening.

PMID- 22367884
TI  - CTCF binds to sites in the major histocompatibility complex that are rapidly
      reconfigured in response to interferon-gamma.
AB  - Activation of the major histocompatibility complex (MHC) by interferon-gamma (IFN
      gamma) is a fundamental step in the adaptive immune response to pathogens. Here,
      we show that reorganization of chromatin loop domains in the MHC is evident
      within the first 30 min of IFN-gamma treatment of fibroblasts, and that further
      dynamic alterations occur up to 6 h. These very rapid changes occur at genomic
      sites which are occupied by CTCF and are close to IFN-gamma-inducible MHC genes.
      Early responses to IFN-gamma are thus initiated independently of CIITA, the
      master regulator of MHC class II genes and prepare the MHC for subsequent
      induction of transcription.

PMID- 22367885
TI  - Comparative study of binding of ovine complement factor H with different Borrelia
      genospecies.
AB  - This study presents the binding of ovine factor H (fH) by various serotypes of
      Borrelia and simultaneously correlates their complement resistance to sheep
      serum. Affinity ligand binding assay was employed to study the binding of
      borrelial proteins to ovine recombinant fH and its truncated forms (short
      consensus repeat, SCR 7 and SCRs 19-20). From a repertoire of 17 borrelial
      strains, only two strains showed affinity to sheep fH. A ~28-kDa protein of
      Borrelia burgdorferi sensu stricto (B. burgdorferi s.s., strain SKT-2) bound full
      length fH as well as SCRs 19-20. This fH-binding protein was further identified
      as complement regulator-acquiring surface protein of B. burgdorferi (BbCRASP-1)
      by MALDI-TOF analysis. Surprisingly, a ~26-kDa protein of Borrelia bissettii
      (DN127) showed affinity to full-length fH but not to SCR 7 and SCRs19-20. In
      complement sensitivity assay, both strains-SKT-2 and DN127-were resistant to
      normal sheep serum. Significant complement resistance of two Borrelia garinii
      strains (G117 and T25) was also observed; however, none of those strains was able
      to bind sheep fH. Our study underscores the need of further exploration of fH
      mediated evasion of complement system by Borrelia in domestic animals.

PMID- 22367886
TI  - Treatment-refractory idiopathic hypereosinophilic syndrome: pitfalls and progress
      with use of novel drugs.

PMID- 22367887
TI  - Probiotics and digestive disease.

PMID- 22367889
TI  - Assessing fracture risk using gradient boosting machine (GBM) models.
AB  - Advanced bone imaging with quantitative computed tomography (QCT) has had limited
      success in significantly improving fracture prediction beyond standard areal bone
      mineral density (aBMD) measurements. Thus, we examined whether a machine learning
      paradigm, gradient boosting machine (GBM) modeling, which can incorporate diverse
      measurements of bone density and geometry from central QCT imaging and of bone
      microstructure from high-resolution peripheral QCT imaging, can improve fracture
      prediction. We studied two cohorts of postmenopausal women: 105 with and 99
      without distal forearm fractures (Distal Forearm Cohort) and 40 with at least one
      grade 2 or 3 vertebral deformity and 78 with no vertebral fracture (Vertebral
      Cohort). Within each cohort, individual bone density, structure, or strength
      variables had areas under receiver operating characteristic curves (AUCs) ranging
      from 0.50 to 0.84 (median 0.61) for discriminating women with and without
      fracture. Using all possible variables in the GBM model, the AUCs were close to
      1.0. Fracture predictions in the Vertebral Cohort using the GBM models built with
      the Distal Forearm Cohort had AUCs of 0.82-0.95, while predictions in the Distal
      Forearm Cohort using models built with the Vertebral Cohort had AUCs of 0.80
      0.83. Attempts at capturing a comparable parametric model using the top variables
      from the Distal Forearm Cohort resulted in resulted in an AUC of 0.81. Relatively
      high AUCs for differing fracture types suggest that an underlying fracture
      propensity is being captured by this modeling approach. More complex modeling,
      such as with GBM, creates stronger fracture predictions and may allow deeper
      insights into information provided by advanced bone imaging techniques. 

PMID- 22367888
TI  - Effects of gut microbes on nutrient absorption and energy regulation.
AB  - Malnutrition may manifest as either obesity or undernutrition. Accumulating
      evidence suggests that the gut microbiota plays an important role in the harvest,
      storage, and expenditure of energy obtained from the diet. The composition of the
      gut microbiota has been shown to differ between lean and obese humans and mice;
      however, the specific roles that individual gut microbes play in energy harvest
      remain uncertain. The gut microbiota may also influence the development of
      conditions characterized by chronic low-level inflammation, such as obesity,
      through systemic exposure to bacterial lipopolysaccharide derived from the gut
      microbiota. In this review, the role of the gut microbiota in energy harvest and
      fat storage is explored, as well as differences in the microbiota in obesity and
      undernutrition.

PMID- 22367890
TI  - Effects of polymorphisms in nucleotide-binding oligomerization domains 1 and 2 on
      biomarkers of the metabolic syndrome and type II diabetes.
AB  - The innate immune receptor toll-like receptor 4 (TLR4) has been implicated in
      mediating some of the effects of dietary lipids on inflammation and type 2
      diabetes (T2D). Similar to TLR4, the nucleotide-binding oligomerization domains
      (Nods) 1 and 2 are also proteins of innate immunity, which can respond to lipids
      and initiate pro-inflammatory signalling that plays a role in the aetiology of
      T2D. The objective was to determine the effect of Nod1 (Glu266Lys) and Nod2
      (Ser268Pro) genotypes on factors associated with the metabolic syndrome (MetS),
      and whether they modify the association between dietary lipids and biomarkers of
      the MetS. Men and women (n = 998) between the ages of 20-29 years were genotyped
      for both polymorphisms, completed a one-month, semiquantitative food frequency
      questionnaire and provided a fasting blood sample. The Glu266Lys polymorphism in
      Nod1 was not associated with any of the biomarkers of the MetS, but modified the
      association between dietary saturated fat (SFA) and insulin sensitivity, as
      measured by HOMA-IR (p for interaction = 0.04). Individuals with the Glu/Glu or
      Glu/Lys genotype showed no significant relationship between dietary SFA and HOMA
      IR (beta = -0.002 +/- 0.006, p = 0.77; and beta = -0.003 +/- 0.006, p = 0.61),
      while those with the Lys/Lys genotype showed a positive association (beta = 0.033
      +/- 0.02, p = 0.03). The Nod2 Ser268Pro polymorphism was not associated with
      components of the MetS and did not modify the relationship between dietary lipid
      intake and the biomarkers of MetS. In summary, the Nod1 Glu266Lys polymorphism
      modifies the relationship between dietary SFA intake and HOMA-IR, suggesting that
      Nod1 may act as an intracellular lipid sensor affecting insulin sensitivity.

PMID- 22367891
TI  - An introduction to natural products isolation.
AB  - Natural products, well known for unique chemical diversity and bioactivity, have
      continued to offer templates for the development of novel scaffolds of drugs.
      With the remarkable developments in the areas of separation science,
      spectroscopic techniques, microplate-based ultrasensitive in vitro assays and
      high-throughput screening (HTS) technologies, natural products research has
      gained momentum in recent years. The pre-isolation analyses of crude extracts or
      fraction from different natural matrices, isolation, online detection and
      dereplication of natural products, studies on chemotaxonomy and biosynthesis,
      chemical finger-printing, quality control of herbal products, and metabolomic
      studies have now become much easier than ever before because of the availability
      of a number of modern sophisticated hyphenated techniques, e.g., GC-MS, LC-PDA,
      LC-MS, LC-FTIR, LC-NMR, LC-NMR-MS, and CE-MS. This introductory chapter presents
      a general overview of the processes involved in natural products research,
      starting from extraction and isolation to elucidation of the structures of
      purified natural products and their bioactivity.

PMID- 22367892
TI  - Initial and bulk extraction of natural products isolation.
AB  - Currently, there is a growing interest in the study of natural products,
      especially as part of drug discovery programs. Secondary metabolites can be
      extracted from a variety of natural sources, including plants, microbes, marine
      animals, insects, and amphibians. This chapter focuses principally on laboratory
      scale processes of initial and bulk extraction from plant and microbial sources.
      With regard to plant natural products, the steps required for the preparation of
      the material prior to extraction, including aspects concerning plant selection,
      collection, identification, drying, and grinding, are detailed. The various
      extraction methods available (maceration, ultrasound-assisted solvent extraction,
      percolation, Soxhlet extraction, pressurized solvent extraction, extraction under
      reflux, steam distillation, and acid/based extraction) are reviewed. Regarding
      microbial natural products, this chapter covers issues relating to the isolation
      and culture of microorganisms and presents the extraction methods available for
      the recovery of microbial metabolites. Methods of minimizing compound
      degradation, artifacts formation, extract contamination with external impurities,
      and enrichment of extracts with desired metabolites are also examined.

PMID- 22367893
TI  - Supercritical fluid extraction in natural products analyses.
AB  - Supercritical fluids (SCFs) are increasingly replacing the organic solvents,
      e.g., n-hexane, chloroform, dichloromethane, or methanol, that are conventionally
      used in industrial extraction, purification, and recrystallization operations
      because of regulatory and environmental pressures on hydrocarbon and ozone
      depleting emissions. In natural products extraction and isolation, supercritical
      fluid extraction (SFE), especially employing supercritical CO(2), has become a
      popular choice. Sophisticated modern technologies allow precise regulation of
      changes in temperature and pressure, and thus manipulation of solvating property
      of the SCF, which helps the extraction of natural products of a wide range of
      polarities. This chapter deals mainly with the application of the SFE technology
      in the natural products extraction and isolation, and outlines various
      methodologies with specific examples.

PMID- 22367894
TI  - Accelerated solvent extraction for natural products isolation.
AB  - Accelerated solvent extraction (ASE((r))), first introduced in 1995, is an
      automated rapid extraction technique that utilizes common solvents at elevated
      temperature and pressure, and thereby increases the efficiency of extraction of
      organic compounds from solid and semisolid matrices. ASE((r)) allows extractions
      for sample sizes 1-100 g in minutes, reduces solvent uses dramatically, and can
      be applied to a wide range of matrices, including natural products.

PMID- 22367895
TI  - Microwave-assisted extraction in natural products isolation.
AB  - Microwave-assisted extraction (MAE) or simply microwave extraction is a
      relatively new extraction technique that combines microwave and traditional
      solvent extraction. Application of microwaves for heating the solvents and plant
      tissues in extraction process, which increases the kinetic of extraction, is
      called microwave-assisted extraction. MAE has a number of advantages, e.g.,
      shorter extraction time, less solvent, higher extraction rate and lower cost,
      over traditional method of extraction of compounds from various matrices,
      especially natural products. The use of MAE in natural products extraction
      started in the late 1980s, and through the technological developments, it has now
      become one of the popular and cost-effective extraction methods available today,
      and several advanced MAE instrumentations and methodologies have become
      available, e.g., pressurized microwave-assisted extraction (PMAE) and solvent
      free microwave-assisted extraction (SFMAE). This chapter provides an overview of
      the MAE and presents a number of specific protocols for natural products
      extraction.

PMID- 22367897
TI  - Isolation of natural products by low-pressure column chromatography.
AB  - This chapter describes the isolation of natural products using low-pressure
      column chromatography (LPLC) and provides a brief summary of the adsorption and
      size exclusion processes involved in LPLC. Different types of stationary phases
      used in both adsorption and size exclusion LPLC are also presented with specific
      examples. Various operational parameters in relation to column packing (both wet
      and dry), column equilibration, sample application, and column development, and a
      summary of generic procedures for adsorption and size exclusion LPLC are also
      incorporated in this chapter. Throughout the chapter, several specific examples
      of the application of LPLC for the isolation of various natural products
      including alkaloids, coumarins, flavones, and saponins from various plants are
      given. Many of these examples include a combination of adsorption and size
      exclusion chromatography to obtain specific compounds.

PMID- 22367896
TI  - An introduction to planar chromatography and its application to natural products
      isolation.
AB  - Thin-layer chromatography (TLC) is an easy, inexpensive, rapid, and the most
      widely used method for the analysis and isolation of small organic natural and
      synthetic products. It also has use in the biological evaluation of organic
      compounds, particularly in the areas of antimicrobial and antioxidant metabolites
      and for the evaluation of acetylcholinesterase inhibitors which have utility in
      the treatment of Alzheimer's disease. The ease and inexpensiveness of use of this
      technique, coupled with the ability to rapidly develop separation and bioassay
      protocols will ensure that TLC will be used for some considerable time alongside
      conventional instrumental methods. This chapter deals with the basic principles
      of TLC and describes methods for the analysis and isolation of natural products.
      Examples of methods for isolation of several classes of natural product are
      detailed and protocols for TLC bioassays are given.

PMID- 22367898
TI  - Isolation of natural products by ion-exchange methods.
AB  - The primary goal of many natural products chemists is to extract, isolate, and
      characterize specific analytes from complex plant, animal, microbial, and food
      matrices. To achieve this goal, they rely considerably on highly sophisticated
      and highly hyphenated modern instrumentation. Yet, the vast majority of modern
      instrumentation typically found in the laboratories of natural products chemists
      is founded on the simple principles of intermolecular forces to achieve
      separation. Ion-exchange chromatography (IEC) is, at heart, the most fundamental,
      and strongest, of these interactions and is considered a relatively inexpensive
      and effective medium in which to "clean-up" a sample. Additionally, IEC offers
      high recoveries of key analytes and offers the ability to modify the stationary
      and mobile phases in order to selectively "catch and release" compounds of
      interest.

PMID- 22367899
TI  - Separation of natural products by countercurrent chromatography.
AB  - Countercurrent Chromatography (CCC) provides the natural product chemist with a
      high-resolution separatory method, which is uniquely applicable to sensitive
      (unstable) compounds and which allows virtually quantitative recovery of the load
      sample. Different instruments use different means of retaining a stationary
      liquid phase. The solvent system (SS) can be chosen to optimize the separatory
      power and the number of systems available is limitless. Several examples are
      provided to illustrate the power of the method and to guide the chemist in choice
      of an appropriate SS.

PMID- 22367900
TI  - Isolation of natural products by preparative high performance liquid
      chromatography (prep-HPLC).
AB  - Preparative HPLC (prep-HPLC) has emerged as a mainstay of natural products
      isolation and purification. The various modes available to date, e.g. normal
      phase, reversed-phase, size exclusion, and ion exchange, can be used to purify
      most classes of natural products. This chapter presents an overview of the
      different modes along with a practical guide as to how to purify a natural
      product using the most robust and widely used of the modes, namely reversed-phase
      prep-HPLC. Instrumentation set-up and detection methods, sample preparation,
      method development, and sample work up are also discussed.

PMID- 22367901
TI  - Isolation of natural products by preparative gas chromatography.
AB  - Chromatography is a process for the separation of compounds from the mixtures.
      Gas chromatography (GC) is one of the most important and common techniques in
      separation science. The main focus of this chapter is to demonstrate a hands-on
      approach to preparative gas chromatography (Prep-GC) technique and its use for
      the isolation of natural products, particularly terpenes and other volatiles.
      Starting from the classification of GC separations, columns, and stationary
      phases, sampling techniques, mobile phases, detectors, and fraction collector
      systems of analytical and preparative gas chromatographic separations are
      comparatively covered in this chapter.

PMID- 22367902
TI  - Hyphenated techniques and their applications in natural products analysis.
AB  - A technique where a separation technique is coupled with an online spectroscopic
      detection technology is known as hyphenated technique, e.g., GC-MS, LC-PDA, LC
      MS, LC-FTIR, LC-NMR, LC-NMR-MS, and CE-MS. Recent advances in hyphenated
      analytical techniques have remarkably widened their applications to the analysis
      of complex biomaterials, especially natural products. This chapter focuses on the
      applications of hyphenated techniques to pre-isolation and isolation of natural
      products, dereplication, online partial identification of compounds,
      chemotaxonomic studies, chemical finger-printing, quality control of herbal
      products, and metabolomic studies, and presents specific examples. However, a
      particular emphasis has been given on the hyphenated techniques that involve an
      LC as the separation tool.

PMID- 22367903
TI  - Extraction of plant secondary metabolites.
AB  - This chapter presents an overview of the preparation of extracts from plants
      using organic solvents, with emphasis on common problems encountered and methods
      for their reduction or elimination. In addition to generally applicable
      extraction protocols, methods are suggested for selectively extracting specific
      classes of plant-derived compounds, and phytochemical procedures are presented
      for the detection of classes of compounds encountered commonly during extraction,
      including selected groups of secondary metabolites and interfering compounds.
      Successful extraction begins with careful selection and preparation of plant
      samples and thorough review of the appropriate literature for suitable protocols
      for a particular class of compounds or plant species. During the extraction of
      plant material, it is important to minimize interference from compounds that may
      co-extract with the target compounds, and to avoid contamination of the extract,
      as well as to prevent decomposition of important metabolites or artifact
      formation as a result of extraction conditions or solvent impurities.

PMID- 22367904
TI  - Isolation of marine natural products.
AB  - Marine macro- and micro-biota offer a wealth of chemically diverse compounds that
      have been evolutionary preselected to modulate biochemical pathways. Many
      industrial and academic groups are accessing this source using advanced
      technology platforms. The previous edition of this chapter offered some practical
      guidance in the process of extraction and isolation of marine natural products
      with more emphasis on the procedures adapted to the physical and chemical
      characteristics of the isolated compounds. Automation and direct integration of
      the isolation technology into high-throughput screening (HTS) systems were also
      reported. In this edition, we refer to some new topics which are heavily
      represented in the literature. These include methods for sampling the deep ocean
      and the procedures for culturing high-pressure-adapted (piezophilic) marine
      microorganisms to be amenable to laboratory investigation. A brief discussion on
      genomic-guided approaches to detect the presence of biosynthetic loci even those
      that are silent or cryptic is also included.

PMID- 22367905
TI  - Isolation of microbial natural products.
AB  - In principle, the isolation of secondary metabolites from microbes does not
      differ from their isolation from other organisms. The extraction procedure may of
      course be quite different, especially if it is carried out in an industrial
      scale, but when an extract containing the metabolites of interest is at hand, it
      is the same palette of adsorbents and chromatographic techniques that provide the
      major tools for the fractionation and eventual isolation of the pure compounds.
      Compared to plants, in which one is sure to find secondary metabolites of certain
      types, e.g., flavonoids, microbes can be expected to produce virtually anything
      and it is important to go about the fractionation procedure with an open mind.
      This chapter presents an overview of preparation of extracts from microbial
      sources, and various methods and strategies involved in the isolation and
      characterization of microbial natural products.

PMID- 22367906
TI  - Extraction and isolation of saponins.
AB  - Due to their special structural features, extraction and isolation of saponins
      poses a serious challenge. Conventional methods have been explored as well as the
      recent, relatively greener, efficient, solvent-economic, time-saving, newer
      methods of extraction. Both traditional and recent methods of isolation are also
      discussed. Finally, examples are given involving both conventional and newer
      methods of extraction and isolation. Though in general it is difficult to use a
      single technique for isolation of saponins, recent literature work seems to point
      to the fact that high speed counter-current separation coupled to evaporative
      light scattering detector (ELSD) gives superior separation. The ELSD appears to
      have circumvented the long-standing problem of saponin detection as most of these
      do not have a chromophore, and hence making UV detection only nonspecific and at
      range 200-210 nm.

PMID- 22367907
TI  - Extraction and isolation of phenolic compounds.
AB  - Phenolic compounds constitute a major class of plant secondary metabolites that
      are widely distributed in the plant kingdom and show a large structural
      diversity. These compounds occur as aglycones or glycosides, as monomers or
      constituting highly polymerized structures, or as free or matrix-bound compounds.
      Furthermore, they are not uniformly distributed in the plant and their stability
      varies significantly. This greatly complicates their extraction and isolation
      processes, which means that a single standardized procedure cannot be recommended
      for all phenolics and/or plant materials; procedures have to be optimized
      depending on the nature of the sample and the target analytes, and also on the
      object of the study. In this chapter, the main techniques for sample preparation,
      and extraction and isolation of phenolic compounds have been reviewed-from
      classical solvent extraction procedures to more modern approaches, such as the
      use of molecularly imprinted polymers or counter-current chromatography.

PMID- 22367908
TI  - Scaling-up of natural products isolation.
AB  - Scaling-up is a way of increasing the quantity without losing the quality. The
      scaling-up is not always straightforward as the yield of the target compound
      becomes more important. The factors that influence scaling-up in a medium scale
      are outlined in this chapter. An example of a scale-up is also provided to
      illustrate some of the principles.

PMID- 22367909
TI  - Follow-up of natural products isolation.
AB  - Follow-up of natural products isolation refers to re-isolation of compound(s) of
      interest in larger amounts for further pharmacological testing, conclusive
      structure elucidation, structure modifications to synthesize analogs for
      structure-activity relationships (SAR) studies, preformulation and formulation
      studies or clinical trials. In addition to conventional synthetic chemistry
      approaches, several other methodologies can be applied for following-up natural
      products isolation. This chapter outlines, with specific examples, various
      strategies and methods involved in follow-up of natural products isolation.

PMID- 22367910
TI  - Natural products isolation in modern drug discovery programs.
AB  - Natural products play a vital role in drug discovery. They have served as the
      basic reference and initiators in drug discovery programs. Natural products as
      pure compounds have been involved in western medicine as drugs or lead compounds
      for drug discovery and development. In traditional medicine, they have been
      involved for a very long time as medicinal extracts, infusions, decoctions, or
      other therapeutic preparations. Modern drug discovery programs require an arsenal
      of drug candidate molecules in pure form whose activities (usually against cells
      or enzymes) are rapidly determined using high-throughput screening (HTS) and
      activities are expected in micro- (MUM) to nanomolar (nM) levels. The difficulty
      in meeting today's standards for drug candidate molecules poses the question: are
      natural products still relevant in modern drug discovery programs? This and other
      issues, including the spectroscopic investigation of crude extracts, are
      discussed.

PMID- 22367911
TI  - Nodular lymphocyte-predominant Hodgkin lymphoma: cytopathologic correlates on
      fine-needle aspiration.
AB  - BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a rare
      subtype of Hodgkin lymphoma, is an indolent tumor with frequent instances of
      disease recurrence but a favorable prognosis. To the best of the authors'
      knowledge, there are only limited descriptions of NLPHL in the cytology
      literature because it was only formally recognized as a distinct entity in 1994.
      METHODS: In the current study, all cases of NLPHL diagnosed on excisional biopsy
      (n = 6 cases) at the study institution between 2000 and 2011 that had undergone
      previous fine-needle aspiration (FNA) were reviewed, with a focus on
      cytomorphologic features. RESULTS: Four of 6 cases were termed benign on FNA;
      however, there was retrospective recognition of characteristic LP cells in all
      cases. Unlike classical Hodgkin lymphoma, the tumor cells of NLPHL were often
      found to be mononucleate and presented in a background of small lymphocytes.
      Other features identified included epithelioid histiocytes and numerous bare
      atypical nuclei. CONCLUSIONS: Cases of NLPHL are commonly misdiagnosed as benign
      reactive lymphoid tissue and therefore a careful search using high magnification
      for LP cells is recommended in the evaluation of lymph node FNAs.

PMID- 22367912
TI  - Incidental versus clinically evident thyroid cancer: a 5-year follow-up study.
AB  - BACKGROUND: The incidence of differentiated thyroid cancer in patients undergoing
      surgery for presumed benign thyroid disease (incidental thyroid cancer) is not
      negligible. The purpose of this study was to verify if incidental thyroid cancers
      have a different clinical course than the clinically evident thyroid cancer.
      METHODS: A group of patients with incidental thyroid cancer (n = 95) has been
      compared to a control group with clinically evident thyroid cancer (n = 93). Both
      the histology and the outcome after a 5-year follow-up have been compared.
      RESULTS: At the univariate analysis, the groups demonstrated significant
      differences in many pathologic features, remnant ablation (p < .001), and
      persistent disease (p = .006). Nevertheless, the multivariate analysis revealed
      that the outcome was not influenced by the preoperative or the incidental
      diagnosis. CONCLUSION: Incidental thyroid cancers show a different pathological
      pattern when compared to clinically evident thyroid cancers. Nonetheless, the
      final outcome is not influenced by preoperative or postoperative diagnosis.
      Hence, patients with incidental thyroid cancer should follow the same
      postoperative protocols of patients with clinically evident thyroid cancer.

PMID- 22367913
TI  - Two new mutations in the HIF2A gene associated with erythrocytosis.

PMID- 22367914
TI  - The MET oncogene transforms human primary bone-derived cells into osteosarcomas
      by targeting committed osteo-progenitors.
AB  - The MET oncogene is aberrantly overexpressed in human osteosarcomas. We have
      previously converted primary cultures of human bone-derived cells into
      osteosarcoma cells by overexpressing MET. To determine whether MET transforms
      mesenchymal stem cells or committed progenitor cells, here we characterize
      distinct MET overexpressing osteosarcoma (MET-OS) clones using genome-wide
      expression profiling, cytometric analysis, and functional assays. All the MET-OS
      clones consistently display mesenchymal and stemness markers, but not most of the
      mesenchymal-stem cell-specific markers. Conversely, the MET-OS clones express
      genes characteristic of early osteoblastic differentiation phases, but not those
      of late phases. Profiling of mesenchymal stem cells induced to differentiate
      along osteoblast, adipocyte, and chondrocyte lineages confirms that MET-OS cells
      are similar to cells at an initial phase of osteoblastic differentiation.
      Accordingly, MET-OS cells cannot differentiate into adipocytes or chondrocytes,
      but can partially differentiate into osteogenic-matrix-producing cells. Moreover,
      in vitro MET-OS cells form self-renewing spheres enriched in cells that can
      initiate tumors in vivo. MET kinase inhibition abrogates the self-renewal
      capacity of MET-OS cells and allows them to progress toward osteoblastic
      differentiation. These data show that MET initiates the transformation of a cell
      population that has features of osteo-progenitors and suggest that MET regulates
      self-renewal and lineage differentiation of osteosarcoma cells.

PMID- 22367915
TI  - Poststroke hemiparesis impairs the rate but not magnitude of adaptation of
      spatial and temporal locomotor features.
AB  - BACKGROUND: Persons with stroke and hemiparesis walk with a characteristic
      pattern of spatial and temporal asymmetry that is resistant to most traditional
      interventions. It was recently shown in nondisabled persons that the degree of
      walking symmetry can be readily altered via locomotor adaptation. However, it is
      unclear whether stroke-related brain damage affects the ability to adapt spatial
      or temporal gait symmetry. OBJECTIVE: Determine whether locomotor adaptation to a
      novel swing phase perturbation is impaired in persons with chronic stroke and
      hemiparesis. METHODS: Participants with ischemic stroke (14) and nondisabled
      controls (12) walked on a treadmill before, during, and after adaptation to a
      unilateral perturbing weight that resisted forward leg movement. Leg kinematics
      were measured bilaterally, including step length and single-limb support (SLS)
      time symmetry, limb angle center of oscillation, and interlimb phasing, and
      magnitude of "initial" and "late" locomotor adaptation rates were determined.
      RESULTS: All participants had similar magnitudes of adaptation and similar
      initial adaptation rates both spatially and temporally. All 14 participants with
      stroke and baseline asymmetry temporarily walked with improved SLS time symmetry
      after adaptation. However, late adaptation rates poststroke were decreased (took
      more strides to achieve adaptation) compared with controls. CONCLUSIONS: Mild to
      moderate hemiparesis does not interfere with the initial acquisition of novel
      symmetrical gait patterns in both the spatial and temporal domains, though it
      does disrupt the rate at which "late" adaptive changes are produced. Impairment
      of the late, slow phase of learning may be an important rehabilitation
      consideration in this patient population.

PMID- 22367916
TI  - Early clinical indicators of developmental outcome in abusive head trauma.
AB  - PURPOSE: The purpose of the study was to determine the developmental prognostic
      significance of early clinical indicators in abusive head trauma. METHODS:
      Seventy-one children were diagnosed with abusive head trauma and followed in a
      post-injury growth and development clinic. A retrospective chart review was
      completed to gather clinical features at the time of injury, including presence
      or absence of early post-traumatic seizures, presence or absence of intubation,
      and presence or absence of pediatric intensive care unit admission. Children then
      underwent developmental testing with use of the Capute Scales of the Cognitive
      Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale
      (CLAMS) during follow-up clinic visits. Clinical features at initial injury were
      compared to developmental outcome. RESULTS: Thirty-four of 71 patients with
      seizures during their admission hospitalization scored significantly lower on
      follow-up developmental testing than patients who did not have seizures. Twenty
      one of 71 patients who required intubation scored lower on developmental testing
      than patients who did not require intubation. Thirty-five of 71 patients who
      required pediatric intensive care unit admission scored lower on developmental
      testing than patients who did not require pediatric intensive care unit
      admission. CONCLUSIONS: This study demonstrates that clinical factors at the time
      of injury, such as early post-traumatic seizures and intubation requirement, are
      associated with poorer developmental outcome. This study also suggests that close
      developmental follow-up should be obtained for all children with abusive head
      trauma, regardless of whether or not the child was admitted to the PICU.

PMID- 22367917
TI  - Use of the NICO Myriad device for tumor and cyst removals in a developing
      country.
AB  - PURPOSE: To describe the use of the NICO Myriad, a new side-cutting aspiration
      device for the resection of tumors, in a developing country. METHODS: The 11-, 13
      , and 15-ga handpieces were used to resect tumors exposed via craniotomies, and
      the 19-ga handpiece was used down the side channel of a Storz Oi endoscope to
      resect tumors exposed endoscopically. RESULTS: The Myriad was used to resect 23
      tumors, including spinal cord tumors, posterior fossa tumors and pineal tumors,
      and the cysts associated with two craniopharyngiomas. No complications were
      associated with the Myriad. Handpieces that were re-sterilized in Steranios after
      the initial use could each be used two to four times thereafter. CONCLUSIONS: The
      Myriad is the first effective tumor removal device that can be introduced down
      the side channel of most endoscopes, greatly expanding the spectrum of tumors
      that can be treated endoscopically. Its minimal diameter allows better visibility
      in small, deep sites such as the pineal region than is usually available when
      ultrasonic aspirators are used. The cost of the device, and particularly the
      handpieces, will limit their utility in developing countries until re-usable
      handpieces are developed.

PMID- 22367918
TI  - Diagnostic value of K-ras mutation analysis for pancreaticobiliary cytology
      specimens with indeterminate diagnosis.
AB  - BACKGROUND: Fine-needle aspiration and bile duct brushing cytology have been
      traditionally used for early detection of pancreaticobiliary malignancy. Quite
      frequently, the cytological interpretations of these specimens are indeterminate.
      In this retrospective study, we evaluated the diagnostic value of detecting K-ras
      (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation in
      pancreaticobiliary cytology specimens that had equivocal cytological diagnoses.
      METHODS: A total of 129 cases that had indeterminate cytology diagnoses, K-ras
      mutational analysis, and histopathological follow-up were retrieved. The
      cytological interpretations, histopathological diagnoses, and K-ras mutation
      results were reviewed and analyzed. RESULTS: Overall, the sensitivity and
      specificity of K-ras mutation for detection of pancreaticobiliary malignancy
      including adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous
      cystic neoplasm were 57% and 94%, respectively. The positive and negative
      predictive values of K-ras mutation for the presence of pancreaticobiliary
      malignancy were 94% and 60%, respectively. CONCLUSIONS: The results demonstrate
      that K-ras mutation has a high predictive value for malignancy in patients with
      indeterminate pancreaticobiliary cytology and should be included as an important
      adjuvant diagnostic marker. It should be noted that a negative K-ras mutation
      result does not rule out malignancy, and K-ras mutation can be detected, although
      infrequently, in morphologically benign conditions.

PMID- 22367919
TI  - Cervical osteomyelitis after placement of a self-expanding plastic stent for
      palliation of dysphagia associated with chemoradiation-induced esophageal
      strictures.
AB  - BACKGROUND: Esophageal strictures are a common sequela of chemoradiation and/or
      surgery to the head and neck cancers and can lead to stenosis and significant
      dysphagia. Endoscopic dilation endoscopic and placement of self-expanding stents
      are often to used relieve dysphagia symptoms. However, these stents are not
      without risks and complications. METHODS: We present a case of a 58-year-old man
      who had the rare complication of cervical osteomyelitis as a result of plastic
      esophageal stent placement for palliation of chemoradiation-induced strictures.
      RESULTS: The patient was successfully managed with immobilization of the cervical
      spine in a halo vest and appropriate antibiotics. CONCLUSION: To the best of our
      knowledge, this is the first reported case of cervical spine osteomyelitis after
      self-expanding plastic stent (SEPS) placement for esophageal stricture. It was
      successfully treated with immobilization and antibiotic therapy. The treating
      physician should be aware of this rare complication to make an early diagnosis.
      Literature on esophageal stent-induced cervical osteomyelitis is reviewed.

PMID- 22367920
TI  - The cognitive genetics of neuropsychiatric disorders.
AB  - Classification in psychiatry is heavily dependent on clinical symptoms and
      illness course. This ignores the critical role that cognitive problems play in
      neuropsychiatric disorders affecting different domains across the lifespan, from
      ADHD and autism to schizophrenia and Alzheimers disease. At this point, it is
      unclear whether cognitive mechanisms are specific to disorders, whether multiple
      processes can contribute to the same disorder, or whether aberrant neural
      processing can result in many different phenotypic outcomes. Understanding this
      would allow us to better grasp normal as well as pathological brain function.
      This could inform diagnostics based on understanding of neurophysiological
      processes and the consequent development of new therapeutics. Genetics, and the
      development of genomic research, offers real opportunities to understand the
      molecular mechanisms relevant to cognition. This chapter defines and describes
      the main cognitive phenotypes, which are investigated in psychiatric disorders.
      We review evidence for their heritability and early progress in the field using
      cytogenetic, linkage and candidate gene-based research methodologies. With high
      throughput genomics it is now possible to explore novel common and rare risk
      variants for psychiatric disorders and their role in cognitive function at a
      genome-wide level. We review the results of early genomic studies and discuss the
      novel insights that they are starting to provide. Finally, we review the analysis
      of whole-genome DNA sequence data and the challenges that this will bring for
      cognitive genomics research.

PMID- 22367922
TI  - Impaired bone health and asymptomatic vertebral compressions in fracture-prone
      children: a case-control study.
AB  - Frequent fractures in children may be a sign of impaired bone health, but it
      remains unestablished when and how fracture-prone children should be assessed.
      This prospective study elucidated skeletal characteristics and predisposing
      factors in children with recurrent fractures. Findings were used to establish
      guidelines for screening. During a 12-month period we recorded fracture history
      for all children (n = 1412) treated for an acute fracture at a large university
      hospital. All apparently healthy children over 4 years of age, who had sustained:
      (1) at least one vertebral fracture; (2) two long-bone fractures before age 10
      years; or (3) three long-bone fractures before age 16 years, were recruited. They
      underwent dual-energy X-ray absorptiometry (DXA), laboratory tests, and spinal
      radiography. Information regarding family history and lifestyle factors were
      collected. Findings were compared with healthy controls. Sixty-six fracture-prone
      children (44 males, mean age 10.7 years; 5% of all children with fractures) were
      identified. Altogether, they had sustained 183 long-bone fractures (median 3,
      range 0-7); 11 children had sustained vertebral fracture(s). Patients had
      significantly lower bone mineral density (BMD) at lumbar spine (p < 0.001), hip
      (p = 0.007), and whole body (p < 0.001) than the controls; only 5 children (8%)
      had a BMD Z-score < -2.0. Asymptomatic vertebral compressions were prevalent,
      especially in those under 10 years of age. Hypercalciuria (11%) and
      hyperphosphaturia (22%) were significantly more prevalent than in controls. Serum
      concentration of 25-hydroxyvitamin D (S-25OHD) was below 50 nmol/L in 55%; low
      levels were associated with low BMD and vertebral compressions. The fracture
      prone children had lower calcium intake, less physical activity, and more often
      had siblings with fractures than the controls. The findings suggest that a
      thorough pediatric evaluation, including DXA and spinal radiography, is often
      indicated already after a second significant low-energy fracture in children, in
      order to detect potentially preventable adverse lifestyle factors and nutritional
      deficits and to identify those with compromised overall bone health.

PMID- 22367923
TI  - Approaches to investigating common bleeding disorders: an evaluation of North
      American coagulation laboratory practices.
AB  - Bleeding disorders commonly result from deficiencies or defects in von Willebrand
      factor (VWF), platelets, coagulation factors, or fibrinolytic proteins. The
      primary goal of our study was to assess current North American coagulation
      laboratory practices for diagnosing bleeding disorders, using an on-line patterns
      of-practice survey of diagnostic laboratory members of the North American
      Specialized Coagulation Laboratory Association. The survey examined laboratory
      approaches to evaluating bleeding disorders, with specific questions about the
      tests and test panels offered and compliance to recent guideline recommendations
      on diagnosing von Willebrand disease (VWD) and platelet function disorders. All
      laboratories responding to the survey performed a prothrombin time/international
      normalized ratio, an activated partial thromboplastin time, and coagulation
      factor assays, and many tested for VWD and platelet disorders. However, few
      laboratories had test panels that evaluated the more common bleeding disorders
      and few performed some assays, including VWF multimer assessments and assays for
      fibrinolytic disorders. Additionally, the cutoffs used by laboratories to
      diagnose type 1 VWD varied considerably, with only a minority following the
      National Heart Lung Blood Institute recommendations. In contrast, laboratories
      that tested for platelet function disorders mostly complied with aggregation
      testing recommendations, as published in the recent North American guidelines.
      Our results indicate that there are some gaps in the strategies used by
      laboratories to diagnose bleeding disorders that might be addressed by
      development of further guidelines and test algorithms that emphasize evaluations
      for common bleeding disorders. Laboratories may also benefit from guidelines on
      test interpretation, and external evaluation of their bleeding disorder testing
      strategies.

PMID- 22367924
TI  - Impact of fullerene particle interaction on biochemical activities in fermenting
      Zymomonas mobilis.
AB  - It has become a concern that increasing applications of fullerene (C(60))
      particles for industrial and, in particular, medical practices can pose potential
      risks to the ecosystem because of their excellent ability for electron uptake and
      reactivity in living organisms. In the present study, the authors explored the
      molecular interactions between bacterial cells and C(60) nanoparticles (nano
      C(60) aggregates and fullerenol) and their impact on biochemical activities of
      Zymomonas mobilis in a fermentation system. Experimental results showed that
      fullerenol demonstrated a considerable impact on cell damage and biochemical
      performance. The ethanol-producing Z. mobilis reacted with the C(60) species and
      performed less ethanol production, while producing more organic acids.
      Microscopic observations indicated that the interactions between the bacterial
      cells and the fullerenols could damage cell membranes and remove cell
      compartments by vesicle exocytosis. The present study indicated that the exposure
      of C(60) species can lead to microbial-nanoparticle interaction and a variation
      of metabolism.

PMID- 22367925
TI  - Susceptibility genes for schizophrenia: mutant models, endophenotypes and
      psychobiology.
AB  - Schizophrenia is characterised by a multifactorial aetiology that involves
      genetic liability interacting with epigenetic and environmental factors to
      increase risk for developing the disorder. A consensus view is that the genetic
      component involves several common risk alleles of small effect and/or rare but
      penetrant copy number variations. Furthermore, there is increasing evidence for
      broader, overlapping genetic-phenotypic relationships in psychosis; for example,
      the same susceptibility genes also confer risk for bipolar disorder. Phenotypic
      characterisation of genetic models of candidate risk genes and/or putative
      pathophysiological processes implicated in schizophrenia, as well as examination
      of epidemiologically relevant gene * environment interactions in these models,
      can illuminate molecular and pathobiological mechanisms involved in
      schizophrenia. The present chapter outlines both the evidence from phenotypic
      studies in mutant mouse models related to schizophrenia and recently described
      mutant models addressing such gene * environment interactions. Emphasis is placed
      on evaluating the extent to which mutant phenotypes recapitulate the totality of
      the disease phenotype or model selective endophenotypes. We also discuss new
      developments and trends in relation to the functional genomics of psychosis which
      might help to inform on the construct validity of mutant models of schizophrenia
      and highlight methodological challenges in phenotypic evaluation that relate to
      such models.

PMID- 22367921
TI  - Genetic models of sensorimotor gating: relevance to neuropsychiatric disorders.
AB  - Sensorimotor gating, or the ability of a sensory event to suppress a motor
      response, can be measured operationally via prepulse inhibition (PPI) of the
      startle response. PPI is deficient in schizophrenia patients as well as other
      neuropsychiatric disorders, can be measured across species, and has been used
      widely as a translational tool in preclinical neuropharmacological and genetic
      research. First developed to assess drug effects in pharmacological and
      developmental models, PPI has become one of the standard behavioral measures in
      genetic models of schizophrenia and other neuropsychiatric disorders that exhibit
      PPI deficits. In this chapter we review the literature on genetic models of
      sensorimotor gating and discuss the utility of PPI as a tool in phenotyping
      mutant mouse models. We highlight the approaches to genetic mouse models of
      neuropsychiatric disease, discuss some of the important caveats to these
      approaches, and provide a comprehensive table covering the more recent genetic
      models that have evaluated PPI.

PMID- 22367926
TI  - Meta-analysis of self-reported substance use compared with laboratory substance
      assay in general adult mental health settings.
AB  - An accurate assessment of substance use is necessary to make a correct
      psychiatric diagnosis and to provide appropriate treatment. This study uses meta
      analysis to establish the strength of the association between self-reported
      substance use and the results of laboratory substance assay including the testing
      for specific substances and screening for any substance use in psychiatric
      hospitals and in community mental health settings. A systematic search for
      published studies was supplemented by additional data required for meta-analysis
      provided by several researchers in this field. Using random-effects meta
      analysis, we calculated the pooled estimate of the odds ratio of a positive
      substance assay in patients reporting use or non-use of substances and estimated
      the sensitivity, specificity, positive predictive value and negative predictive
      value. Twenty-six studies met the inclusion criteria. Very strong associations
      were found between self-reported use and positive tests for cannabis [N = 11
      studies, odds ratio (OR) = 22.3; 95% confidence interval (CI) = 10.1-49.1],
      amphetamines (N = 8, OR = 26.6; 95% CI = 7.9-88.9), cocaine (N = 8, OR = 39.7;
      95% CI = 16.2-97.2) and opiates (N = 7, OR = 83.5; 95% CI = 26.7-260.7). Strong
      associations were found between self-reported use of any substance and positive
      substance screening (N = 15, OR = 7.2, 95% CI = 3.6-14.1) and tests for alcohol
      use (N = 5, OR = 8.5; 95% CI = 2.5-28.4). Screening for any substance use had a
      sensitivity of 61% and a specificity of 66%. Testing for individual substances
      was specific but lacked sensitivity. Screening has the potential to detect
      clinically relevant substances that would not be reported by the patient, whereas
      testing for a specific substance has little advantage over self-report. The
      sensitivity of the substance assay might be improved by obtaining a sample at the
      earliest opportunity. Consideration should be given to the increased use of
      substance screening in general adult mental health settings because it could
      improve the accuracy of psychiatric diagnosis and increase the likelihood of
      patients receiving treatment for substance use disorders.

PMID- 22367927
TI  - Glomus caroticum tumor as rare cause of recurrent syncope.

PMID- 22367928
TI  - HITlights: a career perspective on heparin-induced thrombocytopenia.
AB  - Two decades of research into heparin-induced thrombocytopenia (HIT) permit a
      personal historical perspective on this fascinating syndrome. Previously, the
      frequency of HIT was unknown, although complicating thrombosis was believed to be
      rare and primarily arterial. The opportunity to apply a remarkable test for "HIT
      antibodies"--the (14) C-serotonin-release assay (SRA)--to serial plasma samples
      obtained during a clinical trial of heparin thromboprophylaxis, provided insights
      into the peculiar nature of HIT, such as, its prothrombotic nature--including its
      strong association with venous thrombosis (RR = 11.6 [95%CI, 6.4-20.8; P <
      0.0001); its more frequent occurrence with unfractionated versus low-molecular
      weight heparin; the "iceberg" model, which states that among the many patients
      who form anti-PF4/heparin antibodies during heparin therapy, only a minority
      whose antibodies evince strong platelet-activating properties develop HIT; and
      the characteristic HIT timeline, whereby serum/plasma antibodies are readily
      detectable at or prior to the HIT-associated platelet count fall. Applying the
      SRA also to patients encountered in clinical practice led to recognition of
      warfarin-induced venous limb gangrene (for which HIT is a major risk factor via
      its extreme hypercoagulability) and delayed-onset HIT (whereby thrombocytopenia
      begins or worsens following heparin discontinuation, due to the ability of HIT
      antibodies strongly to activate platelets even in the absence of heparin--so
      called heparin-"independent" platelet activation). Recent concepts include the
      increasing recognition of HIT "overdiagnosis" (due to the low diagnostic
      specificity of the widely-applied PF4-dependent immunoassays), and the
      observation that HIT-associated consumptive coagulopathy is a risk factor for
      treatment failure with PTT-adjusted direct thrombin inhibitor therapy ("PTT
      confounding" secondary to HIT-associated coagulopathy).

PMID- 22367929
TI  - Impact of the BDNF Val66Met polymorphism on cognition: implications for
      behavioral genetics.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth
      factor family and is implicated as a modulator of neuronal survival and
      differentiation, synaptic plasticity, and higher order cognitive functions such
      as learning and memory. A common single-nucleotide polymorphism (SNP) has been
      identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF
      secretion and impairments in specific forms of learning in humans. To better
      understand the impact of this SNP on biological function, the authors generated a
      mouse model containing the BDNF Met allele, which they found to replicate the key
      phenotypes observed in humans and provided further insight into the functional
      impact of this SNP in vivo. They used a "bottom-up" approach to study the BDNF
      SNP, which provided external validation in biologically less complex, genetically
      uniform systems, which minimized the variability inherent in human studies. In
      this review, the authors discuss the impact of the BDNF SNP on learning and
      memory while providing arguments for the relevance of a vertically integrated
      approach to studying human genetic variants.

PMID- 22367930
TI  - Detection of carbonic anhydrase IX protein in the diagnosis of malignant pleural
      effusion by enzyme-linked immunosorbent assay and immunocytochemistry.
AB  - BACKGROUND: Carbonic anhydrase IX (CAIX) is a hallmark of metabolic change in
      cancer cells. The aim was to evaluate the utility of CAIX expression for the
      detection of malignant pleural effusions by enzyme-linked immunosorbent assay
      (ELISA) and immunocytochemistry. METHODS: A total of 97 pleural effusions
      including 54 benign effusions, 10 atypical effusions, and 33 malignant effusions,
      classified based on cytological diagnosis and etiology, were subjected to ELISA
      to measure protein level and to immunocytochemistry in cell blocks to determine
      CAIX expression. RESULTS: CAIX levels were significantly higher in the malignant
      group compared with the benign group. Receiver operating characteristic curve
      analysis of benign and malignant pleural effusion for CAIX indicated an area
      under the curve of 0.82 with a value of 1882 pg/dL as the best threshold for
      distinguishing benign from malignant effusions, which yields a sensitivity,
      specificity, and accuracy of 63.6%, 94.4%, and 82.8%, respectively. None of the
      benign effusion expressed CAIX by immunocytochemistry. Malignant effusion cell
      blocks expressed CAIX in 63.6% of cases with 100% specificity. Upon combination
      of CAIX level and immunocytochemistry to detect malignant pleural effusions, the
      sensitivity and accuracy increased to 81.8% and 89.7%, respectively. The CAIX
      level determined by ELISA and the CAIX expression detected by immunocytochemistry
      were positively correlated. In atypical effusions, 5 cases (50%) exhibited CAIX
      levels higher than the cutoff value or were highlighted by CAIX
      immunocytochemistry. CONCLUSIONS: ELISA and immunocytochemistry methods for
      determination of CAIX protein are potential additional tests for detection of
      malignant pleural effusions.

PMID- 22367931
TI  - Recent findings about the Yersinia enterocolitica phage shock protein response.
AB  - The phage shock protein (Psp) system is a conserved extracytoplasmic stress
      response in bacteria that is essential for virulence of the human pathogen
      Yersinia enterocolitica. This article summarizes some recent findings about Y.
      enterocolitica Psp system function. Increased psp gene expression requires the
      transcription factor PspF, but under non-inducing conditions PspF is inhibited by
      an interaction with another protein, PspA, in the cytoplasm. A Psp-inducing
      stimulus causes PspA to relocate to the cytoplasmic membrane, freeing PspF to
      induce psp gene expression. This PspA relocation requires the integral
      cytoplasmic membrane proteins, PspB and PspC, which might sense an inducing
      trigger and sequester PspA by direct interaction. The subsequent induction of psp
      gene expression increases the PspA concentration, which also allows it to contact
      the membrane directly, perhaps for its physiological function. Mutational
      analysis of the PspB and PspC proteins has revealed that they both positively and
      negatively regulate psp gene expression and has also identified PspC domains
      associated with each function. We also compare the contrasting physiological
      roles of the Psp system in the virulence of Y. enterocolitica and Salmonella
      enterica sv. Typhimurium (S. Typhimurium). In S. Typhimurium, PspA maintains the
      proton motive force, which provides the energy needed to drive ion importers
      required for survival within macrophages. In contrast, in the extracellular
      pathogen Y. enterocolitica, PspB and PspC, but not PspA, are the Psp components
      needed for virulence. PspBC protect Y. enterocolitica from damage caused by the
      secretin component of its type 3 secretion system, an essential virulence factor.

PMID- 22367932
TI  - Stratified distribution of nutrients and extremophile biota within freshwater ice
      covering the surface of Lake Baikal.
AB  - Biological entities and gradients of selected chemicals within the seemingly
      barren ice layers covering Lake Baikal were investigated. Ice cores 40-68 cm long
      were obtained from in shore and offshore sites of Southern Lake Baikal during the
      cold period of a year (March-April) in 2007 and 2008. In microscopic observations
      of the melted ice, both algae and bacteria were found in considerable numbers
      (>10(3) cells/L and >10(4) cells/ml, respectively). Among all organisms found,
      diatom was generally the most predominant taxon in the ice. Interestingly, both
      planktonic and benthic algae were present in considerable numbers (2-4*10(4)
      cells/L). Dominant phototrophic picoplankton were comprised of small green algae
      of various taxa and cyanobacteria of Synechococcus and Cyanobium. The bacterial
      community consisted mostly of short rod and cocci cells, either free-living or
      aggregated. Large numbers of yeast-like cells and actinomycete mycelium were also
      observed. Concentrations of silica, phosphorus, and nitrate were low by an order
      of magnitude where biota was abundant. The profile of the ice could be
      interpreted as vertical stratification of nutrients and biomass due to biological
      activities. Therefore, the organisms in the ice were regarded to maintain high
      activity while thriving under freezing conditions. Based on the results, it was
      concluded that the freshwater ice covering the surface of Lake Baikal is
      considerably populated by extremophilic microorganisms that actively metabolize
      and form a detritus food chain in the unique large freshwater ecosystem of Lake
      Baikal.

PMID- 22367933
TI  - Effects of phosphate addition on biofilm bacterial communities and water quality
      in annular reactors equipped with stainless steel and ductile cast iron pipes.
AB  - The impact of orthophosphate addition on biofilm formation and water quality was
      studied in corrosion-resistant stainless steel (STS) pipe and corrosion
      susceptible ductile cast iron (DCI) pipe using cultivation and culture
      independent approaches. Sample coupons of DCI pipe and STS pipe were installed in
      annular reactors, which were operated for 9 months under hydraulic conditions
      similar to a domestic plumbing system. Addition of 5 mg/L of phosphate to the
      plumbing systems, under low residual chlorine conditions, promoted a more
      significant growth of biofilm and led to a greater rate reduction of disinfection
      by-products in DCI pipe than in STS pipe. While the level of THMs
      (trihalomethanes) increased under conditions of low biofilm concentration, the
      levels of HAAs (halo acetic acids) and CH (chloral hydrate) decreased in all
      cases in proportion to the amount of biofilm. It was also observed that
      chloroform, the main species of THM, was not readily decomposed biologically and
      decomposition was not proportional to the biofilm concentration; however, it was
      easily biodegraded after the addition of phosphate. Analysis of the 16S rDNA
      sequences of 102 biofilm isolates revealed that Proteobacteria (50%) was the most
      frequently detected phylum, followed by Firmicutes (10%) and Actinobacteria (2%),
      with 37% of the bacteria unclassified. Bradyrhizobium was the dominant genus on
      corroded DCI pipe, while Sphingomonas was predominant on non-corroded STS pipe.
      Methylobacterium and Afipia were detected only in the reactor without added
      phosphate. PCR-DGGE analysis showed that the diversity of species in biofilm
      tended to increase when phosphate was added regardless of the pipe material,
      indicating that phosphate addition upset the biological stability in the plumbing
      systems.

PMID- 22367934
TI  - Host species as a strong determinant of the intestinal microbiota of fish larvae.
AB  - We investigated the influence of host species on intestinal microbiota by
      comparing the gut bacterial community structure of four cohabitating freshwater
      fish larvae, silver carp, grass carp, bighead carp, and blunt snout bream, using
      denaturing gradient gel electrophoresis (DGGE) of the amplified 16S and 18S rRNA
      genes. Similarity clustering indicated that the intestinal microbiota derived
      from these four fish species could be divided into four groups based on 16S rRNA
      gene similarity, whereas the eukaryotic 18S rRNA genes showed no distinct groups.
      The water sample from the shared environment contained microbiota of an
      independent group as indicated by both 16S and 18S rRNA genes segments. The
      bacterial community structures were visualized using rank-abundance plots fitted
      with linear regression models. Results showed that the intestinal bacterial
      evenness was significantly different between species (P<0.05) and between species
      and the water sample (P<0.01). Thirty-five relatively dominant bands in DGGE
      patterns were sequenced and grouped into five major taxa: Proteobacteria (26),
      Actinobacteria (5), Bacteroidetes (1), Firmicutes (2), and Cyanobacterial (1).
      Six eukaryotes were detected by sequencing 18S rRNA genes segments. The present
      study suggests that the intestines of the four fish larvae, although reared in
      the same environment, contained distinct bacterial populations, while intestinal
      eukaryotic microorganisms were almost identical.

PMID- 22367935
TI  - Gram-positive rhizobacterium Bacillus amyloliquefaciens FZB42 colonizes three
      types of plants in different patterns.
AB  - The colonization of three types of different plants, Zea mays, Arabidopsis
      thaliana, and Lemna minor, by GFP-labeled Gram-positive rhizobacterium Bacillus
      amyloliquefaciens FZB42 was studied in gnotobiotic systems using confocal laser
      scanning microscopy and electron microscopy. It was demonstrated that FZB42 was
      able to colonize all the plants. On one hand, similar to some Gram-negative
      rhizobacteria like Pseudomonas, FZB42 favored the areas such as the concavities
      in root surfaces and the junctions where lateral roots occurred from the primary
      roots; on the other hand, we clearly demonstrated that root hairs were a popular
      habitat to the Gram-positive rhizobacterium. FZB42 exhibited a specific
      colonization pattern on each of the three types of plants. On Arabidopsis, tips
      of primary roots were favored by FZB42 but not so on maize. On Lemna, FZB42
      accumulated preferably along the grooves between epidermal cells of roots and in
      the concave spaces on ventral sides of fronds. The results suggested L. minor to
      be a promising tool for investigations on plant-microbial interaction due to a
      series of advantages it has. Colonization of maize and Arabidopsis roots by FZB42
      was also studied in the soil system. Comparatively, higher amount of FZB42
      inoculum (~10(8) CFU/ml) was required for detectable root colonization in the
      soil system, where the preference of FZB42 cells to root hairs were also
      observed.

PMID- 22367936
TI  - Growth promotion of Xanthium italicum by application of rhizobacterial isolates
      of Bacillus aryabhattai in microcosm soil.
AB  - This study was conducted using rhizobacteria, which are able to exert beneficial
      effects upon plant growth in the infertile soil collected from barren lakeside
      areas. Four strains of plant growth promoting bacteria were isolated from the
      rhizosphere of a common wild plant, Erigeron canadensis. Isolated strains LS9,
      LS11, LS12, and LS15 were identified as Bacillus aryabhattai by 16S rDNA sequence
      analysis. B. aryabhattai LS9, LS11, LS12, and LS15 could solubilize 577.9, 676.8,
      623.6, and 581.3 mg/L of 0.5% insoluble calcium phosphate within 2 days of
      incubation. Production of indole acetic acid, a typical growth promoting
      phytohormone auxin, by strain LS15 was 471.3 mg/L in 2 days with the addition of
      auxin precursor L-tryptophan. All the strains also produced other phytohormones
      such as indole butyric acid, gibberellins, and abscisic acid, and strain LS15
      showed the highest production rate of gibberellin (GA(3)), 119.0 MUg/mg protein.
      Isolated bacteria were used in a microcosm test for growth of wild plant Xanthium
      italicum, which can be utilized as a pioneer plant in barren lands. Seed
      germination was facilitated, and the lengths of roots, and shoots and the dry
      weights of germinated seedlings after 16 days were higher than those of the
      uninoculated control plants. Root lengths of seedlings of X. italicum increased
      by 121.1% in LS11-treated samples after 16 days. This plant growth-promoting
      capability of B. aryabhattai strains may be utilized as an environmentally
      friendly means of revegetating barren lands, especially sensitive areas such as
      lakeside lands.

PMID- 22367937
TI  - Diversity and physiological properties of root endophytic actinobacteria in
      native herbaceous plants of Korea.
AB  - Endophytic actinobacterial diversity in the native herbaceous plant species of
      Korea was analyzed using a culture-based approach. Sixty one actinobacterial
      strains were isolated, and assigned to 15 genera based on 16S rRNA gene analysis.
      The members of the genus Streptomyces comprised 45.9% of the total isolates,
      followed by Micromonospora (18.8%), Rhodococcus (6.6%), Microbispora (4.9%), and
      Micrococcus (4.9%). Other minor constituents included members of Microbacterium,
      Streptacidiphilus, Arthrobacter, Dietzia, Kitasatospora, Herbiconiux,
      Mycobacterium, Nocardia, Rathayibacter, and Tsukamurella. Among the isolates,
      65.6% exhibited at least one hydrolytic enzyme activity out of four, and 45.9%
      exhibited antagonistic activity against at least one fungal pathogen out of five,
      thus demonstrating that endophytic actinobacteria can be an important source of
      bioactive compounds. Notably, most strains of Streptomyces proved active for both
      enzymatic and antagonistic activities.

PMID- 22367938
TI  - Microflora profiling of infected root canal before and after treatment using
      culture-independent methods.
AB  - This study aimed to profile the microflora in infected root canals before and
      after root canal treatment using culture-independent methods. Six infected root
      canals in single-rooted teeth with periapical lesions from five subjects were
      included. Quantification of total bacteria was performed by real-time PCR with
      primers targeting 16S rRNA genes. PCR products with universal 16S rRNA gene
      primers were cloned and partially sequenced, and bacterial identification at the
      species level was performed by comparative analysis with the GenBank database.
      The concentration of extracted DNA before treatment was higher than that after
      root canal treatment, although the difference was not statistically significant.
      Sequence analysis revealed that oral bacteria such as Fusobacterium,
      Streptococcus, Olsenella, and Pseudoramibacter detected in cases before root
      canal treatment disappeared after treatment. These results suggest that the root
      canal microflora are distinct before and after root canal treatment, and that
      treatment changes the microflora in both quantity and quality.

PMID- 22367939
TI  - Phenotypic and phylogenetic analysis of lactic acid bacteria isolated from forage
      crops and grasses in the Tibetan Plateau.
AB  - A total of 140 lactic acid bacteria (LAB) strains were isolated from corn,
      alfalfa, clover, sainfoin, and Indian goosegrass in the Tibetan Plateau.
      According to phenotypic and chemotaxonomic characteristics, 16S rDNA sequence,
      and recA gene PCR amplification, these LAB isolates were identified as belonging
      to five genera and nine species. Corn contained more LAB species than other
      forage crops. Leuconostoc pseudomesenteroides, Lactococcus lactis subsp. lactis,
      Lactobacillus brevis, and Weissella paramesenteroides were dominant members of
      the LAB population on alfalfa, clover, sainfoin, and Indian goosegrass,
      respectively. The comprehensive 16S rDNA and recA-based approach effectively
      described the LAB community structure of the relatively abundant LAB species
      distributed on different forage crops. This is the first report describing the
      diversity and natural populations of LAB associated with Tibetan forage crops,
      and most isolates grow well at or below 10 degrees C. The results will be
      valuable for the future design of appropriate inoculants for silage fermentation
      in this very cold area.

PMID- 22367940
TI  - Purification and characterization of a novel laccase from the edible mushroom
      Hericium coralloides.
AB  - A novel laccase from the edible mushroom Hericium coralloides was purified by ion
      exchange chromatography on diethylaminoethyl (DEAE) cellulose, carboxymethyl (CM)
      cellulose, and Q-Sepharose columns followed by fast protein liquid chromatography
      gel filtration on a Superdex 75 column. Analysis by gel filtration and SDS-PAGE
      indicated that the protein is a monomer in solution with a molecular mass of 65
      kDa. Its N-terminal amino acid sequence was AVGDDTPQLY, which exhibits partial
      sequence homology to previously isolated laccases. Optimum activity was observed
      at pH 2.2 and at 40 degrees C. The enzyme showed activity toward a variety of
      substrates, the most sensitive of which was 2,2'-azinobis [3-ethylbenzothiazolone
      6-sulfonic acid] diammonium salt (ABTS). The degradation activity toward
      substrates was ABTS > N,N-dimethyl-1,4-phenylenediamine > catechol > 2
      methylcatechol > pyrogallol. The laccase did not exert any antiproliferative
      activity against Hep G2 or MCF 7 tumor cell lines at a concentration of 60 MUM,
      unlike some previously reported mushroom proteins, but showed significant
      activity toward human immunodeficiency virus-1 (HIV-1) reverse transcriptase with
      an IC(50) of 0.06 MUM.

PMID- 22367941
TI  - The PseEF efflux system is a virulence factor of Pseudomonas syringae pv.
      syringae.
AB  - An ATP-binding cassette (ABC) transporter, called the PseEF efflux system, was
      identified at the left border of the syr-syp genomic island of Pseudomonas
      syringae pv. syringae strain B301D. The PseEF efflux system was located within a
      3.3-kb operon that encodes a periplasmic membrane fusion protein (PseE), and an
      ABC-type cytoplasmic membrane protein (PseF). The PseEF efflux system exhibited
      amino acid homology to a putative ABC efflux system (MacAB) of E. coli W3104 with
      identities of 47.2% (i.e., PseE to MacA) and 57.6% (i.e., PseF to MacB). A
      nonpolar mutation within the pseF gene was generated by nptII insertional
      mutagenesis. The resultant mutant strain showed significant reduction in
      secretion of syringomycin (74%) and syringopeptin (71%), as compared to parental
      strain B301D. Quantitative real-time RT-PCR was used to determine transcript
      levels of the syringomycin (syrB1) and syringopeptin (sypA) synthetase genes in
      strain B301D-HK7 (a pseF mutant). Expression of the sypA gene by mutant strain
      B301D-HK7 was approximately 6.9% as compared to that of parental strain B301D,
      while the syrB1 gene expression by mutant strain B301D-HK7 was nearly 14.6%. In
      addition, mutant strain B301D-HK7 was less virulent by approximately 67% than
      parental strain B301D in immature cherry fruits. Mutant strain B301D-HK7 was not
      reduced in resistance to any antibiotics used in this study as compared to
      parental strain B301D. Expression (transcript levels) of the pseF gene was
      induced approximately six times by strain B301D grown on syringomycin minimum
      medium (SRM) supplemented with the plant signal molecules arbutin and D-fructose
      (SRMAF), as compared to that of strain B301D grown on SRM (in the absence of
      plant signal molecules). In addition, during infection of bean plants by P.
      syringae pv. syringae strain B728a, expression of the pseF gene increased at 3
      days after inoculation (dai). More than 180-fold induction was observed in
      transcript levels of the pseF gene by parental strain B728a as compared to strain
      B728a-SL7 (a salA mutant). Thus, the PseEF efflux system, an ABC-type efflux
      system, has an important role in secretion of syringomycin and syringopeptin, and
      is required for full virulence in P. syringae pv. syringae.

PMID- 22367943
TI  - Heat- and cold-shock responses in Fusarium graminearum 3 acetyl- and 15 acetyl
      deoxynivalenol chemotypes.
AB  - Fusarium graminearum Schwabe is the primary cause of Fusarium head blight (FHB)
      in North America. Chemically distinct F. graminearum sub-populations can be
      identified based on the type or composition of deoxynivalenol (DON) mycotoxin
      derivatives, including 3-acetyl (3-ADON) and 15-acetyl (15-ADON). The evaluation
      of randomly selected 3-ADON and 15-ADON isolates, collected from spring wheat
      throughout Canada, was performed using thin layer chromatography (TLC), high
      performance liquid chromatography (HPLC), ice-nucleation activity (INA), and heat
      and cold tolerance tests conducted within a temperature range of -70 degrees C to
      65 degrees C. The results indicated that the 3-ADON sub-population, which is
      responsible for the highest disease severity and has rapidly displaced the 15
      ADON sub-population, produces more DON and zearalenone (ZEA) than the 15-ADON sub
      population when exposed to heat and cold. Following exposures (1 and 2 h) to
      extremely high or low temperatures, 3-ADON isolates exhibited faster mycelial
      growth than 15-ADON isolates. In addition, the warmest temperature at which INA
      activity occurred was in 3-ADON (-3.6 degrees C) vs. 15-ADON (-5.1 degrees C).
      Taken together, these features suggest that the newly emerging 3-ADON sub
      population is more resilient than the resident 15-ADON sub-population. Overall,
      the differences between the two sub-populations could provide new insights into
      FHB epidemiology and if validated under field conditions, may provide important
      information for predicting future FHB epidemics.

PMID- 22367942
TI  - Effects of a dark-septate endophytic isolate LBF-2 on the medicinal plant Lycium
      barbarum L.
AB  - Dark septate endophytes (DSE) are ubiquitous root associated fungi; however, our
      understanding of their ecological function remains unclear. Here, we investigated
      the positive effect of a DSE fungus on its host plant Lycium barbarum L. A DSE
      isolate, LBF-2, isolated from the roots of L. barbarum, was inoculated onto the
      roots of plants, which were grown under greenhouse conditions for five weeks. The
      result of molecular analyses of internal transcribed spacer regions indicated
      that LBF-2 was 96% similar to Paraphoma chrysanthemicola. Melanized septate
      hyphae were observed in the root cortical cells of L. barbarum using a light
      microscope. Inoculation with LBF-2 increased the total biomass by 39.2% and also
      enhanced chlorophyll fluorescence. Inoculation increased the concentration of
      total chlorophyll by 22.8% and of chlorophyll a by 21.3%, relative to
      uninoculated controls. These data indicate that the LBF-2 isolate might be used
      to facilitate the cultivation of L. barbarum, which has medicinal applications.

PMID- 22367944
TI  - Chitinase production by Bacillus thuringiensis and Bacillus licheniformis: their
      potential in antifungal biocontrol.
AB  - Thirty bacterial strains were isolated from the rhizosphere of plants collected
      from Egypt and screened for production of chitinase enzymes. Bacillus
      thuringiensis NM101-19 and Bacillus licheniformis NM120-17 had the highest
      chitinolytic activities amongst those investigated. The production of chitinase
      by B. thuringiensis and B. licheniformis was optimized using colloidal chitin
      medium amended with 1.5% colloidal chitin, with casein as a nitrogen source, at
      30 degrees C after five days of incubation. An enhancement of chitinase
      production by the two species was observed by addition of sugar substances and
      dried fungal mats to the colloidal chitin media. The optimal conditions for
      chitinase activity by B. thuringiensis and B. licheniformis were at 40 degrees C,
      pH 7.0 and pH 8.0, respectively. Na(+), Mg(2+), Cu(2+), and Ca(2+) caused
      enhancement of enzyme activities whereas they were markedly inhibited by Zn(2+),
      Hg(2+), and Ag(+). In vitro, B. thuringiensis and B. licheniformis chitinases had
      potential for cell wall lysis of many phytopathogenic fungi tested. The addition
      of B. thuringiensis chitinase was more effective than that of B. licheniformis in
      increasing the germination of soybean seeds infected with various phytopathogenic
      fungi.

PMID- 22367945
TI  - Saccharomyces cerevisiae Cmr1 protein preferentially binds to UV-damaged DNA in
      vitro.
AB  - DNA metabolic processes such as DNA replication, recombination, and repair are
      fundamentally important for the maintenance of genome integrity and cell
      viability. Although a large number of proteins involved in these pathways have
      been extensively studied, many proteins still remain to be identified. In this
      study, we isolated DNA-binding proteins from Saccharomyces cerevisiae using DNA
      cellulose columns. By analyzing the proteins using mass spectrometry, an
      uncharacterized protein, Cmr1/YDL156W, was identified. Cmr1 showed sequence
      homology to human Damaged-DNA binding protein 2 in its C-terminal WD40 repeats.
      Consistent with this finding, the purified recombinant Cmr1 protein was found to
      be intrinsically associated with DNA-binding activity and exhibited higher
      affinity to UV-damaged DNA substrates. Chromatin isolation experiments revealed
      that Cmr1 localized in both the chromatin and supernatant fractions, and the
      level of Cmr1 in the chromatin fraction increased when yeast cells were
      irradiated with UV. These results suggest that Cmr1 may be involved in DNA-damage
      responses in yeast.

PMID- 22367946
TI  - A selected probiotic strain of Lactobacillus fermentum CM33 isolated from breast
      fed infants as a potential source of beta-galactosidase for prebiotic
      oligosaccharide synthesis.
AB  - Lactic acid bacteria from healthy breast-fed infants were isolated and screened
      for beta-galactosidase production in MRS broth. Among 49 isolates that exhibited
      the yellow clear zone on MRS agar supplemented with bromocresol blue, the isolate
      CM33 was selected as being the highest beta-galactosidase producer and was
      identified as Lactobacillus fermentum based on its morphological characteristics
      and 16S rDNA nucleotide sequence. L. fermentum CM33 exhibited a good survival
      rate under the simulated stomach passage model, comparable to known probiotic
      strains L. gallinarum JCM2011 and L. agilis JCM1187. L. fermentum CM33 was
      antagonistic to pathogenic bacteria Listeria monocytogenes, Escherichia coli
      0157:H7, Salmonella typhi, and Salmonella enteriditis, using the well diffusion
      method. In addition, the selected lactobacilli exhibited a high growth rate when
      cultivated in modified MRS containing commercial galactooligosaccharide (GOS) as
      a sole carbon source, as well as in glucose. A preliminary study on the enzymatic
      synthesis of oligosaccharide using crude beta-galactosidase revealed the
      capability for oligosaccharide synthesis by the transgalactosylation activity.

PMID- 22367947
TI  - Application of multilocus sequence analysis (MLSA) for accurate identification of
      Legionella spp. Isolated from municipal fountains in Chengdu, China, based on 16S
      rRNA, mip, and rpoB genes.
AB  - Legionellosis (Legionnaires' disease; LD) is a form of severe pneumonia caused by
      species of Legionella bacteria. Because inhalation of Legionella-contaminated
      aerosol is considered the major infection route, routine assessments of potential
      infection sources such as hot water systems, air-conditioner cooling water, and
      municipal fountains are of great importance. In this study, we utilized in vitro
      culture and multilocus sequence analysis (MLSA) targeting 16S rRNA, mip, rpoB,
      and mip-rpoB concatenation to isolate and identify Legionella spp. from 5
      municipal fountains in Chengdu City, Sichuan Province, China. Our results
      demonstrated that 16S rRNA was useful for initial identification, as it could
      recognize isolates robustly at the genus level, while the genes mip, rpoB, and
      mip-rpoB concatenation could confidently discriminate Legionella species.
      Notably, the three subspecies of L. pneumophila could be distinguished by the
      analysis based on rpoB. The serotyping result of strain CD-1 was consistent with
      genetic analysis based on the concatenation of mip and rpoB. Despite regular
      maintenance and sanitizing methods, 4 of the 5 municipal fountains investigated
      in this study were positive for Legionella contamination. Thus, regularly
      scheduled monitoring of municipal fountains is urgently needed as well as
      vigilant disinfection. Although the application of MLSA for inspection of
      potential sites of infection in public areas is not standard procedure, further
      investigations may prove its usefulness.

PMID- 22367948
TI  - Effect of Lactobacillus reuteri on the proliferation of Propionibacterium acnes
      and Staphylococcus epidermidis.
AB  - While it is generally accepted that Propionibacterium acnes is involved in the
      development of acne, other bacteria including Staphylococcus epidermidis have
      also been isolated from the acne lesion. The interaction between Lactobacillus
      reuteri, a probiotic bacterium, and acnegenic bacteria is unclear. This study
      examined the effects of L. reuteri on the proliferation of P. acnes and S.
      epidermidis. Human-derived L. reuteri strains (KCTC 3594 and KCTC 3678) and rat
      derived L. reuteri KCTC 3679 were used. All strains exhibited significant
      inhibitory effects on the growth of P. acnes and S. epidermidis. The
      proliferation of P. acnes was decreased by 2-log scales after incubation with L.
      reuteri for 24 h. In addition, the proliferation of S. epidermidis was decreased
      by 3-log scales after incubation with L. reuteri for 24 h, whereas the growth of
      L. reuteri was unaffected by P. acnes or S. epidermidis. Among the L. reuteri
      strains examined, L. reuteri KCTC 3679 had the strongest inhibitory effect on the
      growth of P. acnes and S. epidermidis, followed by L. reuteri KCTC 3594 and L.
      reuteri KCTC 3678. Interestingly, reuterin, an antimicrobial factor, was produced
      only by L. reuteri KCTC 3594. The most pronounced the antibacterial activities of
      L. reuteri were attributed to the production of organic acids. Overall, these
      results suggest that L. reuteri may be a useful probiotic agent to control the
      growth of bacteria involved in acne inflammation and prevent acne.

PMID- 22367949
TI  - Effects of nicotine on the growth and protein expression of Porphyromonas
      gingivalis.
AB  - Tobacco smoking is considered one of the most significant environmental risk
      factors for destructive periodontal disease. The effect of smoking on
      periodontopathic microbiota has not yet been elucidated, as previous studies
      failed to identify a concrete relationship between periodontopathic
      microorganisms and smoking. However, it is likely that smoking, as an
      environmental stress factor, may affect the behavior of dental plaque
      microorganisms, ultimately leading to alteration of the host-parasite
      interaction. The goal of this study was to examine the effect of nicotine, a
      major component of tobacco, on the growth and protein expression of the crucial
      periodontal pathogen Porphyromonas gingivalis. The growth of P. gingivalis 381
      was measured after bacterial cells were cultivated in liquid broth containing
      various nicotine concentrations. First, P. gingivalis cells were allowed to grow
      in the presence of a single dose of nicotine (the single exposure protocol) at 0,
      1, 2, 4, and 8 mg/L, respectively. Second, P. gingivalis cells were exposed to
      five consecutive doses of nicotine (the multiple exposure protocol) at 0, 1, 2,
      and 4 mg/L, respectively. Bacterial growth was measured by optical density and
      protein expression was analyzed by SDS-PAGE and 2-D gel electrophoresis. In the
      single nicotine exposure protocol, it was observed that the growth of P.
      gingivalis 381 was inhibited by nicotine in a dose-dependent manner. In the
      multiple nicotine exposure protocol, the growth rate of P. gingivalis increased
      with each subsequent nicotine exposure, even though bacterial growth was also
      inhibited in a dose dependent fashion. SDS-PAGE and 2-D gel electrophoresis
      analyses revealed a minor change in the pattern of protein expression, showing
      differences in proteins with low molecular weights (around 20 kDa) on exposure to
      nicotine. The results of this study suggest that nicotine exerts an inhibitory
      effect on the growth of P. gingivalis, and has a potential to modulate protein
      expression in P. gingivalis.

PMID- 22367950
TI  - Neutralization potential of the plasma of HIV-1 infected Indian patients in the
      context of anti-V3 antibody content and antiretroviral therapy. [corrected].
AB  - We assessed the anti-V3 antibody content and viral neutralization potential of
      the plasma of 63 HIV-1-infected patients (antiretroviral naive=39, treated=24)
      against four primary isolates (PIs) of clade C and a tier 1 clade B isolate
      SF162. Depletion and inhibition of anti-V3 antibodies in the plasma of five
      patients with high titers of anti-V3 antibodies led to modest change in the
      neutralization percentage against two PIs (range 0-21%). The plasma of
      antiretroviral-treated patients exhibited higher neutralization potential than
      that of the drug-naive plasmas against the four PIs tested which was further
      evidenced by a follow-up study.

PMID- 22367951
TI  - Acinetobacter baumannii outer membrane protein A modulates the biogenesis of
      outer membrane vesicles.
AB  - Acinetobacter baumannii secretes outer membrane vesicles (OMVs) during both in
      vitro and in vivo growth, but the biogenesis mechanism by which A. baumannii
      produces OMVs remains undefined. Outer membrane protein A of A. baumannii
      (AbOmpA) is a major protein in the outer membrane and the C-terminus of AbOmpA
      interacts with diaminopimelate of peptidoglycan. This study investigated the role
      of AbOmpA in the biogenesis of A. baumannii OMVs. Quantitative and qualitative
      approaches were used to analyze OMV biogenesis in A. baumannii ATCC 19606T and an
      isogenic DeltaAbOmpA mutant. OMV production was significantly increased in the
      DeltaAbOmpA mutant compared to wild-type bacteria as demonstrated by quantitation
      of proteins and lipopolysaccharides (LPS) packaged in OMVs. LPS profiles prepared
      from OMVs from wild-type bacteria and the DeltaAbOmpA mutant had identical
      patterns, but proteomic analysis showed different protein constituents in OMVs
      from wild-type bacteria compared to the DeltaAbOmpA mutant. In conclusion, AbOmpA
      influences OMV biogenesis by controlling OMV production and protein composition.

PMID- 22367952
TI  - Leucobacter denitrificans sp. nov., isolated from cow dung.
AB  - The bacterial strain M1T8B10(T) was isolated from cow dung in Suwon, Republic of
      Korea. The strain was a Gram stain-positive rod, nonmotile, and non-spore
      forming. According to 16S rRNA gene sequence analysis, the strain fell within the
      clade of the genus Leucobacter, showing the highest sequence similarities with
      Leucobacter aridicollis L-9(T) (98.7%), Leucobacter iarius 40(T) (98.4%), and
      Leucobacter komagatae JCM 9414(T) (98.2%). Cell-wall peptidoglycan contained the
      diagnostic diamino acid 2,4-diaminobutyric acid of the genus Leucobacter, showing
      B-type cross-linked peptidoglycans. The major fatty acids were anteiso-C(15:0),
      iso-C(16:0), and anteiso-C(17:0). The quinone system consisted of the
      menaquinones MK-11 (78%) and MK-10 (22%). The polar lipid profiles contained
      diphosphatidylglycerol, phosphatidylglycerol, and an unidentified glycolipid.
      Differences in several physiological features including nitrate reduction enabled
      the isolate to be differentiated from all recognized Leucobacter species. Based
      on these phylogenetic, chemotaxonomic, and phenotypic results, the isolate
      represents a novel species, for which the name Leucobacter denitrificans sp. nov.
      is proposed. The type strain is M1T8B10(T) (=KACC 14055(T) =NBRC 106309(T)).

PMID- 22367953
TI  - Comparison of the genetic structures surrounding qnrA1 in Korean Enterobacter
      cloacae and Chinese Escherichia coli strains isolated in the early 2000s:
      evidence for qnrA mobilization via Inc HI2 type plasmid.
AB  - The flanking genetic structure of qnrA1 in Korean Enterobacter loacae was
      identical to that of the Chinese Escherichia coli strain, the first qnrA1
      carrying strain reported in Asia. Analysis of restriction enzyme sites and
      Southern blot hybridization results showed that qnrA1 was transferred between E.
      cloacae and E. coli via Inc HI2 type plasmid.

PMID- 22367954
TI  - Grimontia marina sp. nov., a marine bacterium isolated from the Yellow Sea.
AB  - A novel species belonging to the genus Grimontia is described in this study. A
      Gram-negative, chemoheterotrophic, obligately aerobic, catalase- and oxidase
      positive, motile by a single polar flagellum, and rod-shaped bacterium,
      designated IMCC5001(T), was isolated from surface seawater of the Yellow Sea.
      Strain IMCC5001(T) grew optimally at 30 degrees C in the presence of 3.5% NaCl.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate
      was related most closely to Grimontia hollisae with a sequence similarity of
      95.8%, and formed a robust phyletic lineage with Grimontia hollisae. Differential
      physiological characteristics between the new strain and Grimontia hollisae KCCM
      41680(T) and chemotaxonomic characterization including determination of DNA G+C
      content, fatty acid methyl esters, quinone composition, and polar lipid profiles
      justified the assignment of strain IMCC5001(T) to the genus Grimontia as a novel
      species. In conclusion, strain IMCC5001(T) represents a new species, for which
      the name Grimontia marina sp. nov. is proposed, with the type strain IMCC5001(T)
      (=KCTC 22666(T) =NBRC 105794(T)).

PMID- 22367955
TI  - Involvement of curli fimbriae in the biofilm formation of Enterobacter cloacae.
AB  - In this study, we examined the biofilm forming ability, the mRNA expression of
      curli genes and the morphologies of curli fimbriae and biofilms in clinical
      isolates of Enterobacter cloacae. The csgBA operon was found in 11 (78.6%) of the
      14 isolates. The ability of E. cloacae isolates to form biofilms was
      significantly correlated with the mRNA expression level of the csgA and csgD
      genes. The curli protein fimbriae appeared as tangled fibers and the curli
      proficient strain formed mature biofilms. Our data suggest that the expression of
      the curli fimbriae play an important role in biofilm formation in E. cloacae.

PMID- 22367957
TI  - Treatment of chronic hepatitis C genotype 1 with triple therapy comprising
      telaprevir or boceprevir.
AB  - Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease
      inhibitors, telaprevir and boceprevir, have recently been approved for the
      treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated
      interferon-alpha, ribavirin and telaprevir or boceprevir increases sustained
      virological response rates to ~70% and allows to shorten treatment duration in
      ~1/2 of treatment-naive patients with chronic hepatitis C genotype 1. Sustained
      virological response rates in treatment-experienced patients depend on the
      response to previous treatment, ranging from >80% in previous relapsers to ~30%
      in previous null responders. These advances come at the expense of new adverse
      effects and increased cost. In addition, treatment of chronic hepatitis C will
      become more complex. In these times of changing medical practice, the present
      expert opinion statement by the Swiss Association for the Study of the Liver
      shall provide guidance on the treatment of chronic hepatitis C with triple
      therapy comprising telaprevir or boceprevir.

PMID- 22367958
TI  - Predicting the risk of venous thromboembolism recurrence.
AB  - Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence
      rate. The highest incidence of recurrence is in the first 6 months. Active cancer
      significantly increases the hazard of early recurrence, and the proportions of
      time on standard heparin with an APTT >= 0.2 anti-X(a) U/mL, and on warfarin with
      an INR >= 2.0, significantly reduce the hazard. The acute treatment duration does
      not affect recurrence risk after treatment is stopped. Independent predictors of
      late recurrence include increasing patient age and body mass index, leg paresis,
      active cancer and other persistent VTE risk factors, idiopathic VTE,
      antiphospholipid antibody syndrome, antithrombin, protein C or protein S
      deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D
      dimer. A recommendation for secondary prophylaxis should be individualized based
      on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding.
      The appropriateness of secondary prophylaxis should be continuously reevaluated,
      and the prophylaxis stopped if the benefit no longer exceeds the risk.

PMID- 22367959
TI  - Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal
      neurons.
AB  - The CA3 and CA1 pyramidal neurons are the major principal cell types of the
      hippocampus proper. The strongly recurrent collateral system of CA3 cells and the
      largely parallel-organized CA1 neurons suggest that these regions perform
      distinct computations. However, a comprehensive comparison between CA1 and CA3
      pyramidal cells in terms of firing properties, network dynamics, and behavioral
      correlations is sparse in the intact animal. We performed large-scale recordings
      in the dorsal hippocampus of rats to quantify the similarities and differences
      between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and
      exploration in multiple environments. CA1 and CA3 neurons differed significantly
      in firing rates, spike burst propensity, spike entrainment by the theta rhythm,
      and other aspects of spiking dynamics in a brain state-dependent manner. A
      smaller proportion of CA3 than CA1 cells displayed prominent place fields, but
      place fields of CA3 neurons were more compact, more stable, and carried more
      spatial information per spike than those of CA1 pyramidal cells. Several other
      features of the two cell types were specific to the testing environment. CA3
      neurons showed less pronounced phase precession and a weaker position versus
      spike-phase relationship than CA1 cells. Our findings suggest that these distinct
      activity dynamics of CA1 and CA3 pyramidal cells support their distinct
      computational roles.

PMID- 22367960
TI  - Importance of confirming HER2 overexpression of recurrence lesion in breast
      cancer patients.
AB  - BACKGROUND: The systemic management of metastatic breast cancer (MBC) is usually
      based on ER or HER2 status of the primary tumor. However, the hormonal status or
      the overexpression of human epidermal growth factor 2 (HER2) may change in every
      metastatic site because of the effects of the long-term treatment of metastatic
      cancer with endocrine therapy, chemotherapy, or biological agents. The purpose of
      this study was to investigate the frequency of change in HER2 expression in
      primary and distant metastatic tumors in breast cancer patients. Another
      objective of the study was to examine the effect of the clinical therapy on the
      basis of HER2 expression in a metastatic tumor. MATERIALS AND METHODS: In our
      hospital between 1991 to December 2010, retrospectively, 156 patients had biopsy
      or surgical resection of their metastatic site. All sample were analyzed
      pathologically to confirm metastatic disease and, second, to evaluate HER2 status
      by immunohistochemistry or by FISH. RESULTS: The recurrence lesions were resected
      from the breast or lymph node (n = 67, local lesion), brain (n = 27), lung (n =
      16), liver (n = 20), bone (n = 16), and from the stomach, intestine, ovary, and
      uterus (n = 10). Loss, increase, or no change in HER2 overexpression was observed
      in 3, 5, and 92%, respectively. Positive changes of HER2 in metastatic sites were
      3 (4%) local lesion, 3 (11%) brain, 1 (7%) lung, 0 (0%) liver, 2 (17%) bone, and
      0 (0%) others. In 3 of these 8 patients, trastuzumab was administered. In 2 of 3
      patients, trastuzumab achieved long stable disease. The negative conversion rate
      of HER2 expression in metastatic lesions was 37% in patients treated with
      trastuzumab and 6% in those not treated with trastuzumab, a significant
      difference between the two groups (P < 0.05). CONCLUSIONS: The results of this
      study emphasize the significance of confirming HER2 expression in a recurrence
      lesion. For patients with positive conversion of HER2 status, more treatment
      options may be available. On the other hand, the rate of loss of HER2 expression
      was high in patients treated with trastuzumab, suggesting that the results of
      biopsy may provide an opportunity to reconsider treatment strategies for these
      patients.

PMID- 22367961
TI  - Association of C-terminal region of phosphoglycerate mutase with glycolytic
      complex regulates energy production in cancer cells.
AB  - Cancer cells prefer anaerobic ATP synthesis, regardless of the availability of
      oxygen. It has been hypothesized that in these cells, glycolytic enzymes
      associate into a large complex, which results in an increased efficiency of
      glycolytic flux. However, there is no convincing in vivo evidence supporting this
      hypothesis. Here, we show that all the enzymes of triose phosphate metabolism,
      from aldolase to pyruvate kinase consecutively, form a macromolecular complex in
      vivo and that disruption of such complex significantly inhibits lactate release
      and ATP synthesis in the glycolytic pathway. Composition of the complex and the
      effectiveness of the glycolytic flux depends on lactate and glucose
      concentration. High concentrations of exogenous lactate reduces association of
      the C-terminal region phosphoglycerate mutase (PGAM) with the complex which
      results in its disruption and inhibition of ATP synthesis. Additionally, high
      lactate affects nuclear localization of PGAM and ceases cell proliferation. Our
      findings might provide new prospects for cancer treatment using low-molecular
      weight competitors to destabilize the glycolytic complex and reduce proliferative
      potential of cancer cells.

PMID- 22367964
TI  - A fluorescence-based supramolecular tandem assay for monitoring lysine
      methyltransferase activity in homogeneous solution.
AB  - The demand for practical and convenient enzyme assays for histone lysine
      methyltransferases (HKMTs) emerges along with the rapid development of this young
      class of enzymes. A supramolecular reporter pair composed of p
      sulfonatocalix[4]arene (CX4) and the fluorescent dye lucigenin (LCG) has been
      used to monitor enzymatic trimethylation of lysine residues in peptide
      substrates. The assay affords a switch-ON fluorescence response and operates in a
      continuous, real-time, and label-free fashion. The underlying working principle
      relies on the higher affinity of the macrocycle towards the trimethylated product
      of the enzymatic reaction as compared to the substrate, which allows the assay to
      be carried out in the product-selective mode. The final product incorporates a
      trimethylammonium moiety, a known high-affinity binding motif for CX4. Two
      substrates corresponding to the H3 N-terminal tail, namely, S2 (RTKQTARKSTGGKAP)
      and S6 (QTARKSTGGS), were selected as model compounds for methylation with the
      Neurospora crassa Dim-5 enzyme and investigated by the newly developed
      supramolecular tandem HKMTs assay. Only the longer substrate S2 underwent
      methylation in solution. The potential of the assay for inhibitor screening was
      demonstrated by means of inhibition studies with 1,10-phenanthroline to afford an
      inhibition constant of (70+/-20) MUM.

PMID- 22367965
TI  - Sun protective behaviour of primary and secondary school students in North
      Western Switzerland.
AB  - BACKGROUND: The skin cancer incidence in Switzerland is one of the highest in
      Europe and still on the rise. Sun protection is the main preventive measure and
      of utmost importance during childhood and adolescence, since sunburns within
      these early phases of life increase the risk of developing skin cancer in
      adulthood. OBJECTIVES: The aim of this prospective study, the first of its kind
      in Switzerland, was to investigate the sun protective behaviour of primary and
      secondary school students in Basel (North-Western Switzerland) and to test their
      knowledge about adverse health effects of solar radiation and about protective
      measures. METHODS: Between March and April 2010, supervised classroom surveys
      during regular school lessons were conducted in 13 public schools using a
      multiple-choice questionnaire. 960 questionnaires were handed out to 48 school
      classes. Descriptive statistics and logistic regression analyses were performed
      on the data of 887 (>90%) students from three different grades (3rd, 6th and 9th
      grade). RESULTS: Sun-related knowledge was high in one third of all respondents
      only and significantly depended on student's age and educational background.
      Although the oldest students reached the highest knowledge scores, they protected
      themselves the least from the sun. Sunscreen was the principal form of sun
      protection mentioned, but was insufficiently applied. Seeking shade and wearing
      clothing as protective measures were hardly used. High educational background
      (i.e., of the parents) was a determinant for routine use of sunscreen but was not
      associated with following other sun protective measures. The desire for a suntan
      had no impact on the use of sunscreen, but was a significant predictor for not
      seeking shade and wearing shoulderless shirts when in the sun. More than half of
      all study participants experienced at least one sunburn during the year preceding
      the survey. Fair skin type, higher grade, not seeking shade and wearing
      shoulderless shirts were directly associated with increased odds of sunburn. No
      association was found for the use of sunscreen and the occurrence of sunburn.
      CONCLUSIONS: In order to reduce the incidence of skin cancer in Switzerland, it
      is essential to improve children's and adolescents' sun protective behaviour.
      Future skin cancer prevention campaigns should teach proper use of sunscreen, and
      emphasise the value of wearing clothing and seeking shade as the most effective
      sun protection. Furthermore, major efforts are needed to change adolescents'
      attitude towards a suntan.

PMID- 22367966
TI  - Genome-wide association study identifies novel loci associated with serum level
      of vitamin B12 in Chinese men.
AB  - Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic
      pathways. Clinically, VitB12 deficiency is associated with pernicious anemia,
      neurodegenerative disorder, cardiovascular disease and gastrointestinal disease.
      Although previous genome-wide association studies (GWAS) identified several
      genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in
      European populations, common genetic determinants of VitB12 remain largely
      unknown, especially in Asian populations. Here we performed a GWAS in 1999
      healthy Chinese men and replicated the top findings in an independent Chinese
      sample with 1496 subjects. We identified four novel genomic loci that were
      significantly associated with serum level of VitB12 at a genome-wide significance
      level of 5.00 * 10(-8). These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 *
      10(-15)), CLYBL (13q32; rs41281112; P= 9.23 * 10(-10)), FUT6 (19p13.3; rs3760776;
      P= 3.68 * 10(-13)) and 5q32 region (rs10515552; P= 3.94 * 10(-8)). In addition,
      we also confirmed the association with the serum level of VitB12 for the
      previously reported FUT2 gene and identified one novel non-synonymous single
      nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33;
      rs1047781; P= 3.62 * 10(-36)). The new loci identified offer new insights into
      the biochemical pathways involved in determining the serum level of VitB12 and
      provide opportunities to better delineate the role of VitB12 in health and
      disease.

PMID- 22367968
TI  - High levels of somatic DNA diversity at the myotonic dystrophy type 1 locus are
      driven by ultra-frequent expansion and contraction mutations.
AB  - Several human genetic diseases are associated with inheriting an abnormally large
      unstable DNA simple sequence repeat. These sequences mutate, by changing the
      number of repeats, many times during the lifetime of those affected, with a bias
      towards expansion. These somatic changes lead not only to the presence of cells
      with different numbers of repeats in the same tissue, but also produce
      increasingly longer repeats, contributing towards the progressive nature of the
      symptoms. Modelling the progression of repeat length throughout the lifetime of
      individuals has potential for improving prognostic information as well as
      providing a deeper understanding of the underlying biological process. A large
      data set comprising blood DNA samples from individuals with one such disease,
      myotonic dystrophy type 1, provides an opportunity to parameterize a mathematical
      model for repeat length evolution that we can use to infer biological parameters
      of interest. We developed new mathematical models by modifying a proposed
      stochastic birth process to incorporate possible contraction. A hierarchical
      Bayesian approach was used as the basis for inference, and we estimated the
      distribution of mutation rates in the population. We used model comparison
      analysis to reveal, for the first time, that the expansion bias observed in the
      distributions of repeat lengths is likely to be the cumulative effect of many
      expansion and contraction events. We predict that mutation events can occur as
      frequently as every other day, which matches the timing of regular cell
      activities such as DNA repair and transcription but not DNA replication.

PMID- 22367967
TI  - Tbx1 is a negative modulator of Mef2c.
AB  - The developmental role of the T-box transcription factor Tbx1 is exquisitely
      dosage-sensitive. In this study, we performed a microarray-based transcriptome
      analysis of E9.5 embryo tissues across a previously generated Tbx1 mouse allelic
      series. This analysis identified several genes whose expression was affected by
      Tbx1 dosage. Interestingly, we found that the expression of the gene encoding the
      cardiogenic transcription factor Mef2c was negatively correlated to Tbx1 dosage.
      In vivo data revealed Mef2c up-regulation in the second heart field (SHF) of Tbx1
      null mutant embryos compared with wild-type littermates at E9.5. Conversely,
      Mef2c expression was decreased in the SHF and in somites of Tbx1 gain-of-function
      mutants. These results are consistent with the described role of Tbx1 in
      suppressing cardiac progenitor cell differentiation and indicate also a negative
      effect of Tbx1 on Mef2c during skeletal muscle differentiation. We show that Tbx1
      occupies conserved regulatory regions of the Mef2c locus, suggesting a direct
      effect on Mef2c transcription. However, we also show that Tbx1 interferes with
      the Gata4-> Mef2c regulatory pathway. Overall, our study uncovered a target of
      Tbx1 with critical developmental roles, so highlighting the power of the dosage
      gradient approach that we used.

PMID- 22367969
TI  - An activating Fgfr3 mutation affects trabecular bone formation via a paracrine
      mechanism during growth.
AB  - The fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the
      regulation of endochondral ossification. Fgfr3 gain-of-function mutations cause
      achondroplasia, the most common form of dwarfism, and a spectrum of
      chondrodysplasias. Despite a significant number of studies on the role of FGFR3
      in cartilage, to date, none has investigated the influence of Fgfr3-mediated
      effects of the growth plate on bone formation. We studied three mouse models,
      each expressing Fgfr3 mutation either ubiquitously (CMV-Fgfr3(Y367C/+)), in
      chondrocytes (Col II-Fgfr3(Y367C/+)) or in mature osteoblasts (Col I
      Fgfr3(Y367C/+)). Interestingly, we demonstrated that dwarfism with a significant
      defect in bone formation during growth was only observed in mouse models
      expressing mutant Fgfr3 in the cartilage. We observed a dramatic reduction in
      cartilage matrix mineralization and a strong defect of primary spongiosa.
      Anomalies of primary spongiosa were associated with an increase in osteoclast
      recruitment and a defect of osteoblasts at the mineralization front. A
      significant decrease in bone volume, trabecular thickness and number was also
      observed in the trabecular bone. Interestingly, no anomalies in proliferation and
      differentiation of primary osteoblasts from CMV-Fgfr3(Y367C/+) mice were
      observed. Based on these data, we excluded a potential function of Fgfr3 directly
      on osteoblasts at 3 weeks of age and we obtained evidence that the
      disorganization of the growth plate is responsible for the anomalies of the
      trabecular bone during bone formation. Herein, we propose that impaired FGFR3
      signaling pathways may affect trabecular bone formation via a paracrine mechanism
      during growth. These results redefine our understanding of endochondral
      ossification in FGFR3-related chondrodysplasias.

PMID- 22367971
TI  - Neural correlates of automatic perceptual sensitivity to facial affect in
      posttraumatic stress disorder subjects who survived L'Aquila eartquake of April
      6, 2009.
AB  - The "Emotional Numbing" (EN) constitutes one of the core symptoms in PTSD
      although its exact nature remains elusive. This disorder shows an abnormal
      response of cortical and limbic regions which are normally involved in
      understanding emotions since the very earliest stages of the development of
      processing ability. The aim of our study, which included ten physically healthy
      subjects with PTSD, diagnosed according to DSM-IV-TR, who survived L'Aquila
      earthquake of April 6, 2009, and 10 healthy controls matching for age, sex and
      education, was to examine automatic perceptual sensitivity to facial affect in
      PTSD, through an affective priming task that was administered during functional
      magnetic resonance (fMRI). Behavioural data revealed in the PTSD group a higher
      sensitivity to negative facial affect on an automatic processing level. FMRI data
      analysis revealed that PTSD subjects showed a significantly higher activation in
      right insula and left amygdala that we did not observe in healthy subjects; on
      the contrary, healthy controls showed a greater activation of left lingual gyrus.
      Our data support the hypothesis that PTSD appears to be sensitive to negative
      affect on an automatic processing level and correlates with the activation of
      specific areas involved in processing emotions. An elevated activation of these
      areas may underlie the emotion dysregulation in PTSD and could explain the
      Emotional Numbing symptom associated with this disorder. The present study
      suffers of a number of limitations, for instance, the relatively small sample
      size did not allow the application of alternative statistical models.

PMID- 22367970
TI  - Abnormal interaction between the mitochondrial fission protein Drp1 and
      hyperphosphorylated tau in Alzheimer's disease neurons: implications for
      mitochondrial dysfunction and neuronal damage.
AB  - We recently reported increased mitochondrial fission and decreased fusion,
      increased amyloid beta (Abeta) interaction with the mitochondrial fission protein
      Drp1, increased mitochondrial fragmentation, impaired axonal transport of
      mitochondria and synaptic degeneration in neurons affected by AD. In the present
      study, we extended our previous investigations to determine whether
      phosphorylated tau interacts with Drp1 and to elucidate mitochondrial damage in
      the progression of AD. We also investigated GTPase activity, which is critical
      for mitochondrial fragmentation, in postmortem brain tissues from patients with
      AD and brain tissues from APP, APP/PS1 and 3XTg.AD mice. Using co
      immunoprecipitation and immunofluorescence analyses, for the first time, we
      demonstrated the physical interaction between phosphorylated tau and Drp1.
      Mitochondrial fission-linked GTPase activity was significantly elevated in the
      postmortem frontal cortex tissues from AD patients and cortical tissues from APP,
      APP/PS1 and 3XTg.AD mice. On the basis of these findings, we conclude that Drp1
      interacts with Abeta and phosphorylated tau, likely leading to excessive
      mitochondrial fragmentation, and mitochondrial and synaptic deficiencies,
      ultimately possibly leading to neuronal damage and cognitive decline. Treatment
      designed to reduce the expression of Drp1, Abeta and/or phosphorylated tau may
      decrease the interaction between Drp1 and phosphorylated tau and the interaction
      between Drp1 and Abeta, conferring protection to neurons from toxic insults of
      excessive Drp1, Abeta and/or phosphorylated tau.

PMID- 22367973
TI  - Development of a delirium risk screening tool for long-term care facilities.
AB  - OBJECTIVE: The aim of this study is to develop a delirium risk screening tool for
      use in long-term care (LTC) facilities. METHODS: The sample comprised residents
      aged 65 years and over of seven LTC facilities in Montreal and Quebec City,
      Canada, admitted for LTC. Primary analyses were conducted among residents without
      delirium at baseline. Incident delirium was diagnosed using multiple data sources
      during the 6-month follow-up. Risk factors, all measured at or prior to baseline,
      included the following six groups: sociodemographic, medical, cognitive status,
      physical function, agitated behavior, and symptoms of depression. Variables were
      analyzed individually and by group using Cox regression models. Clinical judgment
      was used to select the most feasible among similarly performing factors. RESULTS:
      The cohort comprised 206 residents without delirium at baseline; 69 cases of
      incident delirium were observed (rate 7.6 per 100 person weeks). The best
      performing screening tool comprised five items, with an overall area under the
      curve of 0.82 (95% CI 0.76, 0.88). These items included brief measures of
      cognitive status, physical function, behavioral, and emotional problems. Using
      cut-points of 2 (or 3) over 5, the scale has a sensitivity of 90% (63%),
      specificity of 59% (85%), and positive predictive value of 52% (66%).
      CONCLUSIONS: This brief screening tool allows nurses to identify LTC residents at
      increased risk for delirium. These residents can be targeted for closer
      monitoring and preventive interventions.

PMID- 22367974
TI  - Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies
      a sensitive period in mouse hippocampal neurodevelopment.
AB  - Iron is a necessary substrate for neuronal function throughout the lifespan, but
      particularly during development. Early life iron deficiency (ID) in humans (late
      gestation through 2-3 yr) results in persistent cognitive and behavioral
      abnormalities despite iron repletion. Animal models of early life ID generated
      using maternal dietary iron restriction also demonstrate persistent learning and
      memory deficits, suggesting a critical requirement for iron during hippocampal
      development. Precise definition of the temporal window for this requirement has
      been elusive due to anemia and total body and brain ID inherent to previous
      dietary restriction models. To circumvent these confounds, we developed
      transgenic mice that express tetracycline transactivator regulated, dominant
      negative transferrin receptor (DNTfR1) in hippocampal neurons, disrupting TfR1
      mediated iron uptake specifically in CA1 pyramidal neurons. Normal iron status
      was restored by doxycycline administration. We manipulated the duration of ID
      using this inducible model to examine long-term effects of early ID on Morris
      water maze learning, CA1 apical dendrite structure, and defining factors of
      critical periods including parvalbmin (PV) expression, perineuronal nets (PNN),
      and brain-derived neurotrophic factor (BDNF) expression. Ongoing ID impaired
      spatial memory and resulted in disorganized apical dendrite structure accompanied
      by altered PV and PNN expression and reduced BDNF levels. Iron repletion at P21,
      near the end of hippocampal dendritogenesis, restored spatial memory, dendrite
      structure, and critical period markers in adult mice. However, mice that remained
      hippocampally iron deficient until P42 continued to have spatial memory deficits,
      impaired CA1 apical dendrite structure, and persistent alterations in PV and PNN
      expression and reduced BDNF despite iron repletion. Together, these findings
      demonstrate that hippocampal iron availability is necessary between P21 and P42
      for development of normal spatial learning and memory, and that these effects may
      reflect disruption of critical period closure by early life ID.

PMID- 22367975
TI  - Current and future management of pediatric venous thromboembolism.
AB  - Venous thromboembolism (VTE) is an increasingly common complication encountered
      in tertiary care pediatric settings. The purpose of this review is to summarize
      the epidemiology, current and emerging pharmacotherapeutic options, and
      management of this disease. Over 70% of VTE occur in children with chronic
      diseases. Although they are seen in children of all ages, adolescents are at
      greatest risk. Pediatric VTE is associated with an increased risk of in-hospital
      mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in
      survivors. In recent years, anticoagulation with low molecular weight heparin has
      emerged as the mainstay of therapy, but compliance is limited by its onerous
      subcutaneous administration route. New anticoagulants either already approved for
      use in adults or in the pipeline offer the possibility of improved dose stability
      and oral routes of administration. Current recommended anticoagulation course
      durations are derived from very limited case series and cohort data, or
      extrapolations from adult literature. However, the pathophysiologic underpinnings
      of pediatric VTE are dissimilar from those seen in adults and are often variable
      within groups of pediatric patients. Clinical studies and trials in pediatric VTE
      are underway which will hopefully improve the quality of evidence from which
      therapeutic guidelines are derived.

PMID- 22367977
TI  - Psychosocial stressors and cigarette smoking among African American adults in
      midlife.
AB  - INTRODUCTION: Psychosocial stress is a significant risk factor for smoking, and
      Blacks experience higher levels of psychosocial stress relative to other
      racial/ethnic groups. Limited research has comprehensively examined psychosocial
      stressors in relation to smoking among Blacks. METHODS: We examined psychosocial
      stressors in relation to smoking status (current, previous, and never) in middle
      aged Blacks (34-85 years, n = 592) from Milwaukee, Wisconsin, a subset of the
      Midlife in the United States Study II (2004-2006). Eleven stressor domains were
      assessed, including psychological and physical work stress, work-family conflict,
      perceived inequality, relationship stress, neighborhood stress, discrimination,
      financial stress, recent problems, stressful events, and childhood adversity. We
      also calculated a cumulative score. Multinomial models were adjusted for age,
      gender, education, and income. RESULTS: Seven of the 11 stressors and the
      cumulative score were associated with higher odds of being a current smoker
      compared with a never-smoker: neighborhood, financial, relationship, and
      psychological work stress, perceived inequality, stressful events, childhood
      adversity (p values <.05; ORs ranged from 1.28 to 1.77). Three stressors and the
      cumulative score were associated with higher odds of being a previous smoker
      versus a never-smoker (p < .05). Individuals who scored in the top quartile on 5
      or more stressors were 3.74 (95% CI = 2.09-6.71) times as likely to be current
      smokers, and more than twice as likely to be previous smokers, compared with
      individuals with no high stressors. CONCLUSIONS: These results demonstrate a
      strong relationship between stress and smoking among urban middle-aged Blacks and
      suggest that cessation programs should address modifiable individual and
      community-level stressors.

PMID- 22367976
TI  - Adherence to varenicline among African American smokers: an exploratory analysis
      comparing plasma concentration, pill count, and self-report.
AB  - INTRODUCTION: Measuring adherence to smoking cessation pharmacotherapy is
      important to evaluating its effectiveness. Blood levels are considered the most
      accurate measure of adherence but are invasive and costly. Pill counts and self
      report are more practical, but little is known about their relationship to blood
      levels. This study compared the validity of pill count and self-report against
      plasma varenicline concentration for measuring pharmacotherapy adherence.
      METHODS: Data were obtained from a randomized pilot study of varenicline for
      smoking cessation among African American smokers. Adherence was measured on Day
      12 via plasma varenicline concentration, pill count, 3-day recall, and a visual
      analogue scale (VAS; adherence was represented on a line with two extremes "no
      pills" and "all pills"). RESULTS: The sample consisted of 55 African American
      moderate to heavy smokers (average 16.8 cigarettes/day, SD = 5.6) and 63.6% were
      female. Significant correlations (p < .05) were found between plasma varenicline
      concentration and pill count (r = .56), 3-day recall (r = .46), and VAS (r =
      .29). Using plasma varenicline concentration of 2.0 ng/ml as the cutpoint for
      adherence, pill count demonstrated the largest area under the receiver operating
      characteristic curve (AUC = 0.85, p = .01) and had 88% sensitivity (95% CI = 75.0
      95.0) and 80% specificity (95% CI = 30.0-99.0) for detecting adherence.
      CONCLUSIONS: Of 3 commonly used adherence measures, pill count was the most valid
      for identifying adherence in this sample of African American smokers. Pill count
      has been used across other health domains and could be incorporated into
      treatment to identify nonadherence, which, in turn, could maximize smoking
      cessation pharmacotherapy use and improve abstinence rates.

PMID- 22367978
TI  - Partners in crime: VEGF and IL-4 conscript tumour-promoting macrophages.
AB  - Tumour-associated macrophages (TAMs) foster tumour progression by several
      mechanisms, including the promotion of angiogenesis, tissue remodelling, and
      immunosuppression. Such pro-tumoural activities are thought to be executed by TAM
      subtypes that harbour features of alternatively activated (or M2-polarized)
      macrophages. However, the molecular signals in tumours that induce recruitment
      and differentiation of M2-like macrophages are not fully defined. In this issue
      of The Journal of Pathology, Linde et al investigate the role of the tumour
      derived cytokines, VEGF and IL-4, in the recruitment and polarization of
      macrophages in a mouse model of skin cancer. The authors report that while VEGF-A
      recruits monocytes from the peripheral circulation, IL-4 induces their
      differentiation into tumour-promoting, M2-like macrophages. IL-4 signalling
      blockade was sufficient to reprogram TAMs away from the M2-like phenotype and
      inhibited tumour angiogenesis and growth. This study attests to the potential of
      reprogramming TAMs to abate their pro-angiogenic and pro-tumoural functions in
      tumours.

PMID- 22367979
TI  - Nitrogen-rich 5,5'-bistetrazolates and their potential use in propellant systems:
      a comprehensive study.
AB  - A large variety of twice-deprotonated nitrogen-rich 5,5'-bistetrazolates, that
      is, the ammonium (1), hydrazinium (2), hydroxylammonium (3), guanidinium (4),
      aminoguanidinium (5), diaminoguanidinium (6), triaminoguanidinium (7), and
      diaminouronium (8) salts, have been synthesized. Energetic compounds 1-8 were
      fully characterized by single-crystal X-ray diffraction (except 8), NMR
      spectroscopy, IR and Raman spectroscopy, and differential scanning calorimetry
      (DSC) measurements. With respect to their potential use in propellant
      applications, the sensitivity towards impact, friction, and electrical discharge
      were determined. Several propulsion and detonation parameters (e.g., heat of
      explosion, detonation velocity) were computed by using the EXPLO5 computer code
      based on calculated (CBS-4M) heats of formation and X-ray densities.
      Additionally, the performance of 1-8 in various formulations was investigated by
      calculating the specific energy and specific impulse of the compounds under
      isochoric conditions.

PMID- 22367980
TI  - Fibroblasts as therapeutic targets in rheumatoid arthritis and cancer.
AB  - Rheumatoid arthritis is a common chronic inflammatory disease that causes
      progressive synovial inflammation resulting in irreversible joint destruction,
      chronic disability and premature mortality. Although it is recognised that in
      rheumatoid arthritis, inflammation and its persistence result from complex
      interactions between haematopoietic and stromal cells, research into the
      pathogenesis of the disease has traditionally concentrated on cells and cytokines
      of the immune system, neglecting the role of stromal cells. As a consequence, new
      biologic treatments have been developed, which have led to a step-change in the
      management of the disease. Nevertheless, these treatments do not reverse tissue
      damage or lead to disease cure and are not effective for all patients.
      Furthermore, at best they induce a significant clinical response (ACR70) in less
      than 60% of patients, most of whom will relapse on treatment withdrawal,
      suggesting that additional therapeutic targets, responsible for complete
      resolution of inflammation, remain to be discovered. An increasing body of
      evidence implicates rheumatoid arthritis synovial fibroblasts in driving the
      persistent, destructive characteristics of the disease. In this paper, we discuss
      the evidence implicating synovial fibroblasts in the pathogenesis of rheumatoid
      arthritis and explore their role as therapeutic targets.

PMID- 22367981
TI  - DNA complex-releasing system by injectable self-setting apatite cement.
AB  - BACKGROUND: The therapeutic effect of plasmid DNA complexes is not satisfactory
      because of the short duration of their gene expression. However, an efficient DNA
      slow-release system has not been established owing to the low dispersion
      stability of the DNA/polycation (or cationic lipid) complexes. We have found that
      hyaluronan (HA) could deposit onto the DNA/polycation complexes, stabilize their
      dispersion and prepare very small particles. We have also reported that the
      injectable self-setting apatite cement has high biocompatibility and
      biodegradability. Thus, durable gene expression systems using injectable apatite
      cement, including DNA/polycation/HA complexes, were expected. METHODS: Small
      DNA/polyethyleneimine (PEI)/HA complex particles were prepared by a lyophilizing
      and rehydration process, and the in vitro release ratio of DNA complex from the
      apatite cements by MLC-6 cells was examined. Apatite cement slurry with collagen
      including plasmid DNA (pDNA) complex [encoding granulocyte macrophage-colony
      stimulating factor (GM-CSF)] was injected close to the tumor subcutaneously
      inoculated into mice. The therapeutic effect and degradation ratio of the apatite
      cement were evaluated. RESULTS: Very fine DNA/PEI/HA complex particles kept being
      dispersed in the apatite cement. The DNA complexes were continuously released
      from the apatite cement by MLC-6 cells. Single injection of the apatite cement
      including pDNA-GM-CSF complex induced complete disappearance of tumor in 60% of
      mice. Smooth degradation of the apatite cement was observed in the mice in which
      a high therapeutic effect was seen. CONCLUSIONS: Single injection of the apatite
      cement-including pDNA-GM-CSF complex showed a high therapeutic effect on solid
      tumor, and thus appears to be promising as a sustained gene expression device.

PMID- 22367982
TI  - Activity scheduling as a core component of effective care management for late
      life depression.
AB  - BACKGROUND: Activity scheduling is an established component of evidenced-based
      treatment for late-life depression in primary care. We examined participant
      records from the Improving Mood-Promoting Access to Collaborative Treatment
      (IMPACT) trial to identify activity scheduling strategies used in the context of
      successful depression care management (CM), associations of activity scheduling
      with self-reported activity engagement, and depression outcomes. METHODS: This
      study used observational mixed methods analysis of 4335 CM session notes from 597
      participants in the intervention arm of the IMPACT trial. Grounded theory was
      used to identify 17 distinct activity categories from CM notes. Logistic
      regression was used to evaluate associations between activity scheduling,
      activity engagement, and depression outcomes at 12 months. All relevant
      institutional review boards approved the research protocol. RESULTS: Seventeen
      distinct activity categories were generated. Most patients worked on at least one
      social and one solitary activity during their course of treatment. Common
      activity categories included physical activity (32%), medication management
      (22%), active-non-physical (19%), and passive (14%) activities. We found
      significant, positive associations between activity scheduling, self-reported
      engagement in activities at 12 months, and depression outcomes at 12 months.
      CONCLUSION: Older primary care patients in CM for depression worked on a wide
      range of activities. Consistent with depression theory that has placed emphasis
      on social activities, the data indicate a benefit for intentional social
      engagement versus passive social and solitary activities. Care managers should
      encourage patients to balance instrumental activities (e.g., attending to medical
      problems) with social activities targeting direct interpersonal engagement.

PMID- 22367983
TI  - Learning-dependent plasticity of hippocampal CA1 pyramidal neuron postburst
      afterhyperpolarizations and increased excitability after inhibitory avoidance
      learning depend upon basolateral amygdala inputs.
AB  - Hippocampal pyramidal neurons in vitro exhibit transient learning-dependent
      reductions in the amplitude and duration of calcium-dependent postburst
      afterhyperpolarizations (AHPs), accompanied by other increases in excitability
      (i.e., increased firing rate, or reduced spike-frequency accommodation) after
      trace eyeblink conditioning or spatial learning, with a time-course appropriate
      to support consolidation of the learned tasks. Both these tasks require multiple
      days of training for acquisition. The hippocampus also plays a role in
      acquisition of single trial inhibitory avoidance learning. The current study
      assessed AHP plasticity in this single-trial learning task using in vitro tissue
      slices prepared at varying intervals posttrial using intracellular current-clamp
      recordings. Reduced AHPs and reduced accommodation were seen in ventral CA1
      pyramidal neurons within 1 h posttraining, plasticity which persisted 24 h but
      was extinguished >72 h posttrial. There was also a reduction in ventral CA1 AHPs
      and accommodation 1 h following simple exposure to the IA apparatus (a novel
      context) but this change was extinguished by 24 h postexposure. Reductions in
      AHPs and accommodation were also seen in dorsal CA1 pyramidal neurons, but were
      delayed until 24 h posttrial and extinguished at >72 h posttrial. Finally,
      transient inactivation of the basolateral complex of the amygdala (with the local
      anesthetics lidocaine or bupivacaine) either immediately before or immediately
      posttrial blocked both learning and learning-dependent changes in excitability in
      the hippocampus assessed 24 h posttrial. CA3 pyramidal neurons showed no
      reductions in AHP peak amplitude or accommodation following IA training or
      context exposure.

PMID- 22367984
TI  - Evaluating the association between endometrial cancer and polycystic ovary
      syndrome.
AB  - BACKGROUND: Given the current lack of clarity in the published literature, we
      performed a systematic review of the literature to determine the exact strength
      of the association between polycystic ovary syndrome (PCOS) and endometrial
      cancer (EC). METHODS: All published studies on the association between PCOS and
      EC identified through MEDLINE (1966-April 2011), EMBASE (1980-April 2011) and
      Cochrane (1998-April 2011). Original data were abstracted where available and
      summarized on a separate Microsoft Excel (2007) database for analysis. A total of
      14 studies comparative and non-comparative were identified and included. RESULTS:
      The non-comparative and comparative data suggested that women with PCOS were more
      likely to develop EC. A meta-analyses of five comparative studies showed an
      increased risk of EC in women with an odds ratio of 2.89 with a 95% confidence
      interval of 1.52-5.48. CONCLUSIONS: Women with PCOS are about three times more
      likely to develop EC compared with women without it. This translates into a 9%
      lifetime risk of EC in Caucasian women with PCOS compared with 3% in women
      without it. Although most women (91%) with PCOS will not develop endometrial
      cancer, our study has shown that they are more likely at increased risk. More
      studies are required to clarify the exact molecular mechanisms, determine the
      best way of screening and preventing disease progression.

PMID- 22367985
TI  - Specificity is rarely absolute in coral-algal symbiosis: implications for coral
      response to climate change.
AB  - Some reef-building corals have been shown to respond to environmental change by
      shifting the composition of their algal symbiont (genus Symbiodinium)
      communities. These shifts have been proposed as a potential mechanism by which
      corals might survive climate stressors, such as increased temperatures.
      Conventional molecular methods suggest this adaptive capacity may not be
      widespread because few (~25%) coral species have been found to associate with
      multiple Symbiodinium clades. However, these methods can fail to detect low
      abundance symbionts (typically less than 10-20% of the total algal symbiont
      community). To determine whether additional Symbiodinium clades are present, but
      are not detected using conventional techniques, we applied a high-resolution,
      real-time PCR assay to survey Symbiodinium (in clades A-D) from 39 species of
      phylogenetically and geographically diverse scleractinian corals. This survey
      included 26 coral species thought to be restricted to hosting a single
      Symbiodinium clade ('symbiotic specialists'). We detected at least two
      Symbiodinium clades (C and D) in at least one sample of all 39 coral species
      tested; all four Symbiodinium clades were detected in over half (54%) of the 26
      symbiotic specialist coral species. Furthermore, on average, 68 per cent of all
      sampled colonies within a given coral species hosted two or more symbiont clades.
      We conclude that the ability to associate with multiple symbiont clades is common
      in scleractinian (stony) corals, and that, in coral-algal symbiosis,
      'specificity' and 'flexibility' are relative terms: specificity is rarely
      absolute. The potential for reef corals to adapt or acclimatize to environmental
      change via symbiont community shifts may therefore be more phylogenetically
      widespread than has previously been assumed.

PMID- 22367986
TI  - Donation after cardiac death in amyotrophic lateral sclerosis: stepping forward
      into uncertain waters.

PMID- 22367987
TI  - Therapeutic devices for epilepsy.
AB  - Therapeutic devices provide new options for treating drug-resistant epilepsy.
      These devices act by a variety of mechanisms to modulate neuronal activity. Only
      vagus nerve stimulation (VNS), which continues to develop new technology, is
      approved for use in the United States. Deep brain stimulation of anterior
      thalamus for partial epilepsy recently was approved in Europe and several other
      countries. Responsive neurostimulation, which delivers stimuli to 1 or 2 seizure
      foci in response to a detected seizure, recently completed a successful
      multicenter trial. Several other trials of brain stimulation are in planning or
      underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive
      method to stimulate cortex. Controlled studies of TMS are split on efficacy,
      which may depend on whether a seizure focus is near a possible region for
      stimulation. Seizure detection devices in the form of shake detectors via
      portable accelerometers can provide notification of an ongoing tonic-clonic
      seizure, or peace of mind in the absence of notification. Prediction of seizures
      from various aspects of electroencephalography (EEG) is in early stages.
      Prediction appears to be possible in a subpopulation of people with refractory
      seizures, and a clinical trial of an implantable prediction device is underway.
      Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG
      activity and seizures, but engineering problems remain in its implementation.
      Optogenetics is a new technique that can control excitability of specific
      populations of neurons with light. Inhibition of epileptiform activity has been
      demonstrated in hippocampal slices, but use in humans will require more work. In
      general, devices provide useful palliation for otherwise uncontrollable seizures,
      but with a different risk profile than with most drugs. Optimizing the place of
      devices in therapy for epilepsy will require further development and clinical
      experience.

PMID- 22367988
TI  - High-frequency oscillations as a new biomarker in epilepsy.
AB  - The discovery that electroencephalography (EEG) contains useful information at
      frequencies above the traditional 80Hz limit has had a profound impact on our
      understanding of brain function. In epilepsy, high-frequency oscillations (HFOs,
      >80Hz) have proven particularly important and useful. This literature review
      describes the morphology, clinical meaning, and pathophysiology of epileptic
      HFOs. To record HFOs, the intracranial EEG needs to be sampled at least at
      2,000Hz. The oscillatory events can be visualized by applying a high-pass filter
      and increasing the time and amplitude scales, or EEG time-frequency maps can show
      the amount of high-frequency activity. HFOs appear excellent markers for the
      epileptogenic zone. In patients with focal epilepsy who can benefit from surgery,
      invasive EEG is often required to identify the epileptic cortex, but current
      information is sometimes inadequate. Removal of brain tissue generating HFOs has
      been related to better postsurgical outcome than removing the seizure onset zone,
      indicating that HFOs may mark cortex that needs to be removed to achieve seizure
      control. The pathophysiology of epileptic HFOs is challenging, probably involving
      populations of neurons firing asynchronously. They differ from physiological HFOs
      in not being paced by rhythmic inhibitory activity and in their possible origin
      from population spikes. Their link to the epileptogenic zone argues that their
      study will teach us much about the pathophysiology of epileptogenesis and
      ictogenesis. HFOs show promise for improving surgical outcome and accelerating
      intracranial EEG investigations. Their potential needs to be assessed by future
      research.

PMID- 22367989
TI  - Wide variation and rising utilization of stroke magnetic resonance imaging: data
      from 11 states.
AB  - OBJECTIVE: Neuroimaging is an essential component of the acute stroke evaluation.
      Magnetic resonance imaging (MRI) is more accurate than computed tomography (CT)
      for the diagnosis of stroke, but is more costly and time-consuming. We sought to
      describe changes in MRI utilization from 1999 to 2008. METHODS: We performed a
      serial cross-sectional study with time trends of neuroimaging in patients with a
      primary International Classification of Diseases, 9th Edition, Clinical
      Modification discharge diagnosis of stroke admitted through the emergency
      department in the State Inpatient Databases from 10 states. MRI utilization was
      measured by Healthcare Cost and Utilization Project criteria. Data were included
      for states from 1999 to 2008 where MRI utilization could be identified. RESULTS:
      A total of 624,842 patients were hospitalized for stroke in the period of
      interest. MRI utilization increased in all states. Overall, MRI absolute
      utilization increased 38%, and relative utilization increased 235% (28% of
      strokes in 1999 to 66% in 2008). Over the same interval, CT utilization changed
      little (92% in 1999 to 95% in 2008). MRI use varied widely by state. In 2008, MRI
      utilization ranged from a low of 55% of strokes in Oregon to a high of 79% in
      Arizona. Diagnostic imaging was the fastest growing component of total hospital
      costs (213% increase from 1999 to 2007). INTERPRETATION: MRI utilization during
      stroke hospitalization increased substantially, with wide geographic variation.
      Rather than replacing CT, MRI is supplementing it. Consequently, neuroimaging has
      been the fastest growing component of hospitalization cost in stroke. Recent
      neuroimaging practices in stroke are not standardized and may represent an
      opportunity to improve the efficiency of stroke care.

PMID- 22367990
TI  - A channelopathy contributes to cerebellar dysfunction in a model of multiple
      sclerosis.
AB  - OBJECTIVE: Cerebellar dysfunction in multiple sclerosis (MS) contributes
      significantly to disability, is relatively refractory to symptomatic therapy, and
      often progresses despite treatment with disease-modifying agents. We previously
      observed that sodium channel Nav1.8, whose expression is normally restricted to
      the peripheral nervous system, is present in cerebellar Purkinje neurons in a
      mouse model of MS (experimental autoimmune encephalomyelitis [EAE]) and in humans
      with MS. Here, we tested the hypothesis that upregulation of Nav1.8 in cerebellum
      in MS and EAE has functional consequences contributing to symptom burden.
      METHODS: Electrophysiology and behavioral assessment were performed in a new
      transgenic mouse model overexpressing Nav1.8 in Purkinje neurons. We also
      measured EAE symptom progression in mice lacking Nav1.8 compared to wild-type
      littermates. Finally, we administered the Nav1.8-selective blocker A803467 in the
      context of previously established EAE to determine reversibility of MS-like
      deficits. RESULTS: We report that, in the context of an otherwise healthy nervous
      system, ectopic expression of Nav1.8 in Purkinje neurons alters their
      electrophysiological properties, and disrupts coordinated motor behaviors.
      Additionally, we show that Nav1.8 expression contributes to symptom development
      in EAE. Finally, we demonstrate that abnormal patterns of Purkinje neuron firing
      and MS-like deficits in EAE can be partially reversed by pharmacotherapy using a
      Nav1.8-selective blocker. INTERPRETATION: Our results add to the evidence that a
      channelopathy contributes to cerebellar dysfunction in MS. Our data suggest that
      Nav1.8-specific blockers, when available for humans, merit study in MS.

PMID- 22367991
TI  - Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance.
AB  - OBJECTIVE: Little is known about the composition of middle cerebral artery (MCA)
      plaques and how they relate to clinical status. Using high-resolution magnetic
      resonance imaging (HR-MRI), we aimed to examine the occurrence of high signal on
      T1-weighted fat-suppressed images (HST1) of MCA plaques, which are highly
      suggestive of fresh or recent intraplaque hemorrhage. METHODS: We retrospectively
      analyzed the HR-MRI and clinical data of 107 adult patients with high-grade
      (>70%) MCA stenosis. On HR-MRI, HST1 within an MCA plaque was defined as an area
      with an intensity >150% of the signal of adjacent muscles. The relationship
      between HST1 and clinical presentations was analyzed. RESULTS: A total of 109
      stenotic MCAs (46 symptomatic and 63 asymptomatic) on 981 image slices were
      analyzed. HST1 was revealed on HR-MRI in 11 vessels (10.1%, 9 symptomatic and 2
      asymptomatic). The occurrence rate of HST1 between symptomatic and asymptomatic
      MCAs was significantly different (19.6% vs 3.2%, p = 0.01). INTERPRETATION: HST1
      within MCA plaque on HR-MRI is associated with ipsilateral stroke. Our results
      provide new insight into the vascular biology of MCA atherosclerosis.

PMID- 22367992
TI  - Predictors of highly prevalent brain ischemia in intracerebral hemorrhage.
AB  - OBJECTIVE: This study was undertaken to determine the prevalence,
      characteristics, risk factors, and temporal profile of concurrent ischemic
      lesions in patients with acute primary intracerebral hemorrhage (ICH). METHODS:
      Patients were recruited within a prospective, longitudinal, magnetic resonance
      imaging (MRI)-based study of primary ICH. Clinical, demographic, and MRI data
      were collected on all subjects at baseline and 1 month. RESULTS: Of the 138
      patients enrolled, mean age was 59 years, 54% were male, 73% were black, and 84%
      had a history of hypertension. At baseline, ischemic lesions on diffusion
      weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were
      present in 27%, and of these lesions, 83% were new and not present at baseline.
      ICH volume (p = 0.025), intraventricular hemorrhage (p = 0.019), presence of
      microbleeds (p = 0.024), and large, early reductions in mean arterial pressure (p
      = 0.003) were independent predictors of baseline DWI lesions. A multivariate
      logistical model predicting the presence of 1-month DWI lesions included history
      of any prior stroke (p = 0.012), presence of 1 or more microbleeds (p = 0.04),
      black race (p = 0.641), and presence of a DWI lesion at baseline (p = 0.007).
      INTERPRETATION: This study demonstrates that >1/3 of patients with primary ICH
      have active cerebral ischemia at baseline remote from the index hematoma, and 1/4
      of patients experience ongoing, acute ischemic events at 1 month. Multivariate
      analyses implicate blood pressure reductions in the setting of an active
      vasculopathy as a potential underlying mechanism. Further studies are needed to
      determine the impact of these lesions on outcome and optimal management
      strategies to arrest vascular damage.

PMID- 22367993
TI  - Prognosis of coma after therapeutic hypothermia: a prospective cohort study.
AB  - OBJECTIVE: This study was designed to establish the reliability of neurologic
      examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked
      potentials (SEPs) to predict poor outcome in patients treated with mild
      hypothermia after cardiopulmonary resuscitation (CPR). METHODS: This multicenter
      prospective cohort study included adult comatose patients admitted to the
      intensive care unit (ICU) after CPR and treated with hypothermia (32-34 degrees
      C). False-positive rates (FPRs 1 - specificity) with their 95% confidence
      intervals (CIs) were calculated for pupillary light responses, corneal reflexes,
      and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after
      reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs
      during hypothermia and after rewarming. The primary outcome was poor outcome,
      defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1
      3) after 6 months. RESULTS: Of 391 patients included, 53% had a poor outcome.
      Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes
      (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR
      3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable
      predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels
      were not. INTERPRETATION: In patients with persisting coma after CPR and
      therapeutic hypothermia, use of motor score or NSE, as recommended in current
      guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor
      outcomes can reliably be predicted by testing brainstem reflexes 72 hours after
      CPR and performing SEP.

PMID- 22367994
TI  - Olesoxime accelerates myelination and promotes repair in models of demyelination.
AB  - OBJECTIVE: Multiple sclerosis is a neurodegenerative disease characterized by
      episodes of immune attack of oligodendrocytes leading to demyelination and
      progressive functional deficit. One therapeutic strategy to address disease
      progression could consist in stimulating the spontaneous regenerative process
      observed in some patients. Myelin regeneration requires endogenous
      oligodendrocyte progenitor migration and activation of the myelination program at
      the lesion site. In this study, we have tested the ability of olesoxime, a
      neuroprotective and neuroregenerative agent, to promote remyelination in the
      rodent central nervous system in vivo. METHODS: The effect of olesoxime on
      oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis was
      tested directly in organotypic slice cultures and OPC-neuron cocultures. Using
      naive animals and different mouse models of demyelination, we morphologically and
      functionally assessed the effect of the compound on myelination in vivo. RESULTS:
      Olesoxime accelerated oligodendrocyte maturation and enhanced myelination in
      vitro and in vivo in naive animals during development and also in the adult brain
      without affecting oligodendrocyte survival or proliferation. In mouse models of
      demyelination and remyelination, olesoxime favored the repair process, promoting
      myelin formation with consequent functional improvement. INTERPRETATION: Our
      observations support the strategy of promoting oligodendrocyte maturation and
      myelin synthesis to enhance myelin repair and functional recovery. We also
      provide proof of concept that olesoxime could be useful for the treatment of
      demyelinating diseases.

PMID- 22367995
TI  - Late motor decline after accomplished remyelination: impact for progressive
      multiple sclerosis.
AB  - OBJECTIVE: To investigate the impact of single or repeated episodes of reversible
      demyelination on long-term locomotor performance and neuroaxonal integrity, and
      to analyze the myelin proteome after remyelination and during aging. METHODS:
      Long-term locomotor performance of previously cuprizone-treated animals was
      monitored using the motor skill sequence (MOSS). Quantitative analysis of myelin
      proteome and histopathological analysis of neuronal/axonal integrity was
      performed after successful remyelination. Histopathological findings observed in
      experimental chronic remyelinated lesions were verified in chronic remyelinated
      lesions from multiple sclerosis (MS) patients. RESULTS: Following cessation of
      cuprizone treatment, animals showed an initial recovery of locomotor performance.
      However, long after remyelination was completed (approximately 6 months after the
      last demyelinating episode), locomotor performance again declined in remyelinated
      animals as compared to age-matched controls. This functional decline was
      accompanied by brain atrophy and callosal axonal loss. Furthermore, the number of
      acutely damaged amyloid precursor protein-positive (APP+) axons was still
      significantly elevated in long-term remyelinated animals as compared to age
      matched controls. Confocal analysis revealed that a substantial proportion of
      these APP+ spheroids were ensheathed by myelin, a finding that was confirmed in
      the chronic remyelinated lesions of MS patients. Moreover, quantitative analysis
      of myelin proteome revealed that remyelinated myelin displays alterations in
      composition that are in some aspects similar to the myelin of older animals.
      INTERPRETATION: We propose that even after completed remyelination, axonal
      degeneration continues to progress at a low level, accumulating over time, and
      that once a threshold is passed axonal degeneration can become functionally
      apparent in the long-term. The presented model thus mimics some of the aspects of
      axonal degeneration in chronic progressive MS.

PMID- 22367996
TI  - Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.
AB  - OBJECTIVE: Huntington disease-like 2 (HDL2) is a progressive, late onset
      autosomal dominant neurodegenerative disorder, with remarkable similarities to
      Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG
      orientation, the repeat is located within the alternatively spliced exon 2A of
      junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas
      on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine.
      The JPH3 protein product serves to stabilize junctional membrane complexes and
      regulate neuronal calcium flux. We have previously demonstrated the potential
      pathogenic properties of JPH3 transcripts containing expanded CUG repeats. The
      aim of this study was to test the possibility that loss of JPH3 expression or
      expanded amino acid tracts also contribute to HDL2 pathogenesis. METHODS:
      Transcripts from the HDL2 locus, and their protein products, were examined in
      HDL2, HD, and control frontal cortex. The effect of loss of Jph3 was examined in
      mice with partial or complete loss of Jph3. RESULTS: Bidirectional transcription
      occurs at the HDL2 locus, although expression of antisense transcripts with
      expanded CAG repeats is limited. Protein products with expanded amino acid tracts
      were not detected in HDL2 brain. However, JPH3 transcripts and full-length JPH3
      protein are decreased in HDL2 brain, and Jph3 hemizygous and null mice exhibit
      abnormal motor function. INTERPRETATION: Our results suggest that the pathogenic
      mechanism of HDL2 is multifactorial, involving both a toxic gain of function of
      JPH3 RNA and a toxic loss of JPH3 expression.

PMID- 22367997
TI  - Nigral pathology and parkinsonian signs in elders without Parkinson disease.
AB  - OBJECTIVE: Motor symptoms such as mild parkinsonian signs are common in older
      persons, but little is known about their underlying neuropathology. We tested the
      hypothesis that nigral pathology is related to parkinsonism in older persons
      without Parkinson disease (PD). METHODS: More than 2,500 persons participating in
      the Religious Orders Study or the Memory and Aging Project agreed to annual
      assessment of parkinsonism with a modified version of the Unified Parkinson
      Disease Rating Scale and brain donation. Brains from 744 deceased participants
      without PD were assessed for nigral neuronal loss and alpha-synuclein
      immunopositive Lewy bodies. RESULTS: Mean age at death was 88.5 years. Mean
      global parkinsonism was 18.6 (standard deviation, 11.90). About 1/3 of cases had
      mild or more severe nigral neuronal loss, and about 17% had Lewy bodies. In
      separate regression models that adjusted for age, sex, and education, nigral
      neuronal loss and Lewy bodies were both related to global parkinsonism (neuronal
      loss: estimate, 0.231; standard error [SE], 0.068; p < 0.001; Lewy bodies:
      estimate, 0.291; SE, 0.133; p = 0.029). Employing a similar regression model that
      included both measures, neuronal loss remained associated with global
      parkinsonism (neuronal loss: estimate, 0.206; SE, 0.075; p = 0.006). By contrast,
      the association between Lewy bodies and global parkinsonism was attenuated by
      >60% and was no longer significant (Lewy bodies: estimate, 0.112; SE, 0.148; p =
      0.447), suggesting that neuronal loss may mediate the association of Lewy bodies
      with global parkinsonism. INTERPRETATION: Nigral pathology is common in persons
      without PD and may contribute to loss of motor function in old age.

PMID- 22367998
TI  - Seven-Tesla magnetic resonance images of the substantia nigra in Parkinson
      disease.
AB  - OBJECTIVE: To investigate anatomical changes in the substantia nigra (SN) of
      Parkinson disease (PD) patients with age-matched controls by using ultra-high
      field magnetic resonance imaging (MRI). METHODS: We performed 7T MRI in 10 PD and
      10 age-matched control subjects. Magnetic resonance images of the SN were
      obtained from a 3-dimensional (3D) T(2)*-weighted gradient echo sequence. Region
      of interest-based 3D shape analysis was performed to quantitatively compare
      images from the 2 groups. RESULTS: The boundary between the SN and crus cerebri
      was not smooth in PD subjects. Undulation in the lateral surface of the SN
      appeared more intense in the side contralateral to that with the more severe
      symptoms, and more prominent at the rostral level of the SN than at the
      intermediate or caudal levels. In addition to the lateral surface, there was a
      striking difference in the dorsomedial aspects of the SN between PD and control
      subjects. In control subjects, a brighter signal region was observed along the
      dorsomedial surface of the lateral portion of SN, whereas in PD subjects, this
      region was observed as a dark region containing a hypointense signal in T(2)*
      weighted images. The measurement of SN volumes, normalized to the intracranial
      volumes, showed higher values in PD subjects than in control subjects.
      INTERPRETATION: This study demonstrates that 3D 7T MRI can definitively visualize
      anatomical alterations occurring in the SN of PD subjects. Further pathological
      studies are required to elucidate the nature of these anatomical alterations.

PMID- 22367999
TI  - Adenosine A2A receptor gene disruption protects in an alpha-synuclein model of
      Parkinson's disease.
AB  - To investigate the putative interaction between chronic exposure to adenosine
      receptor antagonist caffeine and genetic influences on Parkinson's disease (PD),
      we determined whether deletion of the adenosine A(2A) receptor in knockout (KO)
      mice protects against dopaminergic neuron degeneration induced by a mutant human
      alpha-synuclein (hm(2)-alphaSYN) transgene containing both A53T and A30P. The
      A(2A) KO completely prevented loss of dopamine and dopaminergic neurons caused by
      the mutant alpha-synuclein transgene without altering levels of its expression.
      The adenosine A(2A) receptor appears required for neurotoxicity in a mutant alpha
      synuclein model of PD. Together with prior studies the present findings
      indirectly support the neuroprotective potential of caffeine and more specific
      A(2A) antagonists.

PMID- 22368000
TI  - Stem cell therapy for Parkinson's disease.

PMID- 22368002
TI  - Nonequivalence of equivalence methods.

PMID- 22368004
TI  - New translational research center generates controversy among scientists.

PMID- 22368006
TI  - Modern care for neurological problems must address waste.

PMID- 22368008
TI  - Excited state properties and energy transfer within dipyrrin-based binuclear
      iridium/platinum dyads: the effect of ortho-methylation on the spacer.
AB  - Luminescent cyclometalated iridium complexes based on pyridyl appended dipyrrin
      ligands were prepared and characterized both in the solid state and in solution.
      The functionalization of the peripheral pyridyl moiety causes dramatic changes on
      the emission properties of both mono- and hetero- binuclear complexes. A detailed
      photophysical investigation of the two mononuclear derivatives of the
      [(Ppy)(2)Ir(dpm-py)] family (Ppy=2-phenylpyridine, dpm-py=5-(4-pyridyl)dipyrrin)
      was carried out. Introduction of methyl groups at the 3 and 5 positions on the
      pyridyl unit diminishes the non-radiative rate constant by locking the peripheral
      pyridyl group orthogonally to the dipyrrinato plane. Thus, they limit the
      rotational degree of freedom, as well as the charge-transfer character of the
      excited state. The coordination of these two complexes to a cyclometalated
      [(dppy)Pt] fragment (dppy=2,6-diphenylpyridine) led to the formation of binuclear
      species in which the iridium and platinum complexes behave as acceptors and
      donors, respectively. In these heterobinuclear compounds, the methyl groups do
      not influence the energy transfer efficiency, which is estimated to be above 90
      %. However, they do limit the charge-transfer character of the acceptor's excited
      state, as well as its rotational degree of freedom, thus avoiding the detrimental
      effect upon the photophysical performance.

PMID- 22368009
TI  - [Trend of surgical multimodality treatment for advanced gastric cancer].
AB  - Gastric cancer remains one of the most common causes of cancer-related death in
      China. Radical operation is the only potentially curative therapy for advanced
      gastric cancer (AGC). D2 radical gastrectomy has been widely accepted as a
      standard surgical procedure for patients with AGC in China. Several clinical
      trials have revealed that more extended resection than D2 surgery has no impact
      on survival. In order to improve the prognosis of AGC patients, it is necessary
      to carry out the preoperative TNM staging for selecting a reasonable
      therapeutical modality before surgery. Multimodality treatment involving
      perioperative chemotherapy, radiotherapy or molecular targeting agents in
      addition to surgery have been thought to be promising treatment strategy. In this
      article, we present an update on the current literature regarding the trends of
      surgical multimodal treatment for the patients with AGC.

PMID- 22368010
TI  - [New perspectives on medical treatment of gastric cancer].
AB  - Perioperative chemotherapy for gastric cancer has made steady progress with the
      application of chemotherapeutic agents and conduct of relevant clinical trials.
      However, palliative chemotherapy has only made marginal progress, and the median
      survival remains between 8-10 months. An emerging understanding of tumor biology,
      cellular and molecular mechanisms has revealed novel targets in gastric cancer
      therapy, such as trastuzumab, bevacizumab, cetuximab, etc. There are still some
      problems in clinical practice due to the high heterogeneity of gastric cancer
      including optimization of perioperative chemotherapy regimen, determination of
      right strategy to personalize chemotherapy or target therapy for advanced gastric
      cancer. In order to practically achieve individualized therapy, multicenter,
      prospective, randomized clinical trials according specific matters of gastric
      cancer should be performed in China. A deeper understanding of the biological
      characteristics of gastric cancer, and more translational medicine research and
      multi-disciplinary team collaboration should be carried out to achieve
      personalized medicine.

PMID- 22368011
TI  - [Technical aspects of D2 lymphadenectomy for gastric cancer].
AB  - Surgery is the mainstay treatment of the multidisciplinary therapy for  gastric
      cancer. The majority of gastric cancer patients in China are diagnosed at the
      advanced stage. D2 lymphadenectomy is of clinical significance in China. The
      technical aspects of performing a D2 lymphadenectomy require a significant degree
      of training and expertise. In this article, the focus is on the dissection of
      lymph nodes including No.4Sb, No.5-6, No.8a, No.9-11, No.12a, and No.14-15.

PMID- 22368012
TI  - [Surgical treatment for gastric cancer based on T staging according to Gastric
      Cancer Treatment Guidelines].
AB  - The Japanese Gastric Cancer Treatment Guidelines (the Guidelines), as a guiding
      and programmatic document in the treatment for gastric cancer, has drawn high
      attention worldwide. The treatment selection and determination is mainly based on
      the T staging. Endoscopic therapy, laparoscopic surgery and minimal extent
      surgery have consisted of the main clinical practice for T1 cancer. D2 dissection
      is a standard procedure for advanced cancer(T2-T4). Extensive resection or
      neoadjuvant preoperative chemotherapy is recommended for highly advanced cancer.
      Progress in gastric cancer treatment has been acquired recently due to high-level
      clinical trials, new anti-cancer drugs application, and efficiency of
      chemotherapy. Therefore, traditional extensive resection has been abandoned
      gradually. Comprehensive treatment based on chemotherapy could improve survival
      for patients with unresectable and recurrent gastric cancer.

PMID- 22368013
TI  - [Intraperitoneal slow released chemotherapy for advanced gastric cancer].
AB  - Regional lymph node recurrence is no longer the prominent concern regarding the
      prognosis of gastric cancer patients since the establishment of the standard D2
      dissection procedure. Peritoneal metastasis has become the most prominent
      clinical problem. The treatment strategy for peritoneal metastasis includes
      intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy and
      intraperitoneal chemotherapy with drug delivery systems. Intraperitoneal
      chemotherapy has pharmacokinetic advantage when used in combination with drug
      delivery systems. Intraperitoneal chemotherapy with drug delivery systems is an
      effective treatment and prevention method.

PMID- 22368014
TI  - [Chemotherapy selection through the process of gastric cancer].
AB  - The role of chemotherapy has become more and more important in the whole process
      of gastric cancer. S-1 or XELOX regimen is regarded as the standard treatment
      option in adjuvant chemotherapy. First-line chemotherapy in advanced gastric
      cancer has been established to improve survival, and the benefit from second-line
      chemotherapy is being acknowledged. More studies are needed to assess the
      neoadjuvant chemotherapy.

PMID- 22368015
TI  - [Robotic-assisted radical gastrectomy using da Vinci robotic system: a report of
      41 cases].
AB  - OBJECTIVE: To investigate the feasibility and safety of da Vinci robotic-assisted
      radical gastrectomy for gastric cancer. METHODS: Forty-one patients with gastric
      cancer from Southwest Hospital between March 2010 and December 2011 underwent da
      Vinci robotic-assisted radical gastrectomy including total gastrectomy(n=12) and
      distal gastrectomy (n=29). RESULTS: Conversion was required in two patients. One
      was converted to open surgery, and the other to conventional laparoscopic
      surgery. The remaining thirty-nine patients underwent da Vinci robotic-assisted
      radical gastrectomy successfully. The mean operative time was (285+/-61) min for
      total gastrectomy, and (225+/-39) min for distal gastrectomy. The mean blood loss
      was (180+/-157) ml in total gastrectomy, and (150+/-127) ml in distal
      gastrectomy. The mean number of harvested lymph nodes was 34.2+/-18.5. The mean
      time for gastrointestinal function recovery was (3.1+/-1.2) days. The time to
      ambulation was (2.7+/-1.5) days. The time to oral liquid intake was (3.7+/-1.5)
      days. Two patients had complication including wound infection and pneumonia.
      After follow up ranging from 1 to 21 months (median 11 months), 4 patients died
      from peritoneal metastasis, 1 survived with tumor, and the remaining 36 patients
      survived without disease. CONCLUSIONS: da Vinci robotic-assisted radical
      gastrectomy is a feasible and safe surgical procedure with clear operation field,
      precise dissection, minimal trauma and fast recovery.

PMID- 22368016
TI  - [Clinicopathological characteristics and prognostic factors in patients with
      stage III gastric cancer].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics and prognostic
      factors of stage III gastric cancer. METHODS: A retrospectively study of 1007
      patients with Stage III gastric cancer in a single institute in China was
      performed. The patients underwent surgical resection from January 1991 to
      December 2005. Univariate and multivariate analyses were performed using log-rank
      test and Cox proportional hazards model to access the prognostic factors in stage
      III gastric cancer patients who received curative (R0) gastric resection.
      RESULTS: The mean age of the 1007 patients was 58.7 years and the male-to-female
      ratio was 2.6:1.0. There were 242 patients with stage IIIA disease, 403 patients
      with stage IIIB, and 362 patients with stage IIIC. R0, R1, and R2 resection were
      performed in 754 patients (74.9%), 56 patients (5.5%), and 197 patients (19.6%),
      respectively. The 5-year survival rate (37.8%) of patients who received R0
      resection was significant higher than that of patients who received R1(21.2%) and
      R2(8.9%) resection (P<0.05). Multivariate analysis revealed that pN stage, pT
      stage, and Borrmann type were independent prognostic factors (all P<0.01).
      CONCLUSIONS: Stage III gastric cancer patients have certain clinicopathological
      characteristics and R0 resection should be performed if possible. Lymph node
      count, depth of tumor invasion, and Borrmann type are independent prognostic
      factors in stage III gastric cancer patients undergoing R0 resection.

PMID- 22368017
TI  - [Risk factors for early recurrence after radical resection of proximal gastric
      cancer].
AB  - OBJECTIVE: To explore the risk factors for early recurrence (recurrence within 2
      years) of proximal gastric cancer after radical resection. METHODS: The clinical
      data of 367 proximal gastric cancer patients who underwent radical resection in
      the Cancer Institute and Hospital of Tianjin Medical University between January
      2000 and May 2006 were reviewed. Among them, there are 71 patients (19.3%) with
      early recurrence. Univariate analysis and multivariate analysis were applied to
      investigate risk factors for early recurrence. RESULTS: Univariate analysis
      showed that Borrmann type (P<0.01), histology type (P<0.01), depth of invasion
      (P<0.05), negative lymph nodes count (P<0.05) were risk factors for early
      recurrence of proximal gastric. On multivariate analysis, histology type
      (P<0.05), depth of invasion (P<0.05), negative lymph nodes counts (P<0.05) were
      independent risk factors for early recurrence of proximal gastric cancer.
      Negative lymph nodes in early recurrence patients were 8.4 +/- 7.2, which were
      significantly less as compared to patients without early recurrence (10.7 +/-
      8.7) (P<0.05). CONCLUSION: For T3 proximal gastric adenosquamous cancer, extended
      resection and lymphadenectomy should be considered. Intraoperative or
      postoperative adjuvant treatment should be administered as routine.

PMID- 22368018
TI  - [Lymph node metastasis and prognosis of gastric cancer without serosal invasion].
AB  - OBJECTIVE: To evaluate the impact of lymph node metastasis on the prognosis of
      gastric cancer without serosal invasion. METHODS: From January 1994 to December
      2005, 616 gastric cancer patients without serosal invasion and 162 gastric cancer
      patients with serosal invasion underwent D2 or D2(+) lymphadenectomy.
      Clinicopathologic data and long-term survival of the two groups were analyzed
      retrospectively. RESULTS: The 5-year survival rate of patients with gastric
      cancer without serosal invasion was 77.9%, significantly higher than that of
      patients with gastric cancer with serosal invasion (37.3%) (P<0.01). The 5-year
      survival rates of T1a(M), T1b(SM), T2(MP), T3(SS), T4(SE,SI) were 95.6%, 92.5%,
      73.5%, 62.7%, and 37.3%, respectively. As classified in the 13th edition of
      Gastric Cancer Treatment Guidelines in Japan, the 5-year survival rates of
      patients with gastric cancer without serosal invasion were 91.5% in N0, 75.3% in
      N1, 54.8% in N2, 14.7% in N3, and the differences were statistically significant
      (P<0.01). According to 7th edition of TNM classification, the 5-year survival
      rates of N0, N1, N2, N3a, N3b for the study group were 91.5%, 83.6%, 59.8%,
      17.2%, 11.8%, respectively (P<0.01). Lymph node metastasis was an independent
      prognostic risk factor (P<0.01). CONCLUSIONS: In patients with gastric cancer
      without serosal invasion, lymph node metastasis is an predictive factor
      regardless it is based on the extent or the number of lymph node metastasis.

PMID- 22368019
TI  - [Prognostic value of metastatic lymph node ratio in gastric cancer].
AB  - OBJECTIVES: To evaluate the value of the metastatic to examined lymph nodes (rN)
      ratio in gastric cancer patients who underwent radical resection. METHODS: In
      this retrospective study, data were collected from the medical records of 710
      patients who underwent radical gastrectomy (R0) for gastric cancer from 1980 to
      2006 in the Department of Surgical Oncology at the First Affiliated Hospital of
      China Medical University. The patients were divided into 2 groups according to
      the number of examined lymph nodes: Group 1 consisted of 327 patients with <15
      examined lymph nodes and Group 2 consisted of 383 patients with >=15 lymph nodes.
      rN categories staging and pN categories were divided separately according to the
      metastatic lymph node ratio and the examined lymph nodes. The prognostic factors
      were analyzed by univariate (Log-rank) and multivariate (Cox model) analysis
      methods. RESULTS: The median survival time was 74 months (95% CI:55.6-92.4
      months) in Group 1 and 96 months (95% CI:77.8-119.2 months) in Group 2, and the
      difference was not statistically significant (P>0.05). On multivariate analysis,
      the N ratio remained as an independent prognostic factor in both Group 1 (P<0.01,
      RR=1.225, 95% CI:1.102-1.362) and Group 2 (P<0.01, RR=1.421, 95% CI:1.269-1.592).
      However, pN stage was an independent prognostic factor only in Group 1. When the
      rN ratio classification was applied, there were no significant differences
      between each categories (P>0.05). However, the overall survival of patients with
      pN1 disease in Group 1 was significantly shorter than that in Group 2 according
      to the pN stage classification (P<0.01). CONCLUSIONS: The metastatic lymph node
      ratio is an independent prognostic factor of the prognosis of gastric cancer. The
      staging system based on metastatic lymph node ratio (rN) is more reliable than
      the system based on the number of metastatic lymph nodes in the prediction of the
      prognosis of gastric cancer.

PMID- 22368020
TI  - [Pattern of lymph node metastasis and extent of lymphadenectomy for distal
      gastric cancer].
AB  - OBJECTIVE: To analyze lymph node (LN) metastasis patterns and determine the
      appropriate extent of LN dissection in distal-third gastric cancer. METHODS:
      Clinical data of 545 patients with distal third gastric cancer undergoing radical
      operation in the Fujian Provincial Hospital between 2001 and 2010 were analyzed
      retrospectively. The metastasis rate for each LN station was analyzed stratified
      by the depth of tumor invasion. RESULTS: The incidence of LN metastasis in this
      cohort was 38.2% (208/545). LN metastasis rate in mucosal cancer was 2.0% (2/99)
      and involved LNs were limited to station 1 LN stations. LN metastasis rate in
      submucosal cancer was 18.9% (18/95), significantly higher than that in mucosal
      cancer (P<0.01). The metastasis rates to groups No.7, 8 and 9 in station 2 were
      5.3% (5/94), 3.2% (3/94), and 1.1% (1/89) respectively. In addition, 3 cases
      (3.2%) had metastasis in station 2 outside the range of groups 7, 8 and 9
      including groups No.1, 11p and 12. Gastric cancer invading the muscularis propria
      or deeper layers showed an significant increased rate of metastasis (P<0.01).
      CONCLUSION: D1 dissection seems to be sufficient for mucosal cancer. Standard D2
      dissection should be performed for cancers of the muscularis propria or deeper.
      For submucosal cancer, an extended D1+ dissection is required for complete
      removal of metastatic nodes.

PMID- 22368021
TI  - [Necessity of No.13 lymph node dissection in advanced gastric carcinoma].
AB  - OBJECTIVE: To investigate the feasibility and necessity of No.13 lymph node
      dissection for advanced gastric carcinoma. METHODS: Clinical data of 144 cases
      who were diagnosed as TNMII-III stage gastric carcinoma were collected from
      January 2007 to December 2009 in the Department of General Surgery at the First
      Affiliated Hospital of Nanchang University. Seventy-two cases who received D2
      radical gastrectomy plus No.13 lymph node dissection were selected as the study
      group, and they were matched 1:1 to 72 cases who received D2 Radical gastrectomy
      (the control group) for TNMII-III stage gastric carcinoma. The differences in the
      intraoperative and postoperative parameters and survival time were compared, and
      the factors associated with No.13 lymph node metastasis were analyzed. RESULTS:
      There were no significant differences between the two groups in operative time
      [(2.8 +/- 0.4) h vs. (2.7 +/- 0.4) h], blood loss [(191.9 +/- 81.5) ml vs. (186.0
      +/- 81.7) ml], the incidence of postoperative complications (18.1% vs. 15.3%),
      length of hospital stay [(12.3 +/- 4.2) d vs. (11.9 +/- 3.2) d] and 3-year
      survival rate (63% vs. 57%) (all P>0.05). In the study group, there were 15
      patients (20.8%) with positive No.13 lymph nodes, and the 3-year survival rate
      was 13%, significantly lower compared to those with negative No.13 lymph node
      (73%, n=57) (P<0.05). Multivariate analysis showed that N stage (P<0.01) and
      histological type (P<0.05) were independently associated with No.13 lymph node
      metastasis. CONCLUSION: No.13 lymph node dissection for TNMII-III stage gastric
      cancer is feasible and necessary.

PMID- 22368022
TI  - [Laparoscopy-assisted combined radical resection for synchronous rectal and
      gastric cancer in elderly patients: report of two cases].
AB  - OBJECTIVE: To investigate the safety and feasibility of laparoscopy-assisted
      combined radical resection for synchronous rectal and gastric cancer in elderly
      patients. METHODS: Clinical data of two elderly patients undergoing laparoscopy
      assisted combined radical resection for synchronous rectal and gastric cancer
      were analyzed retrospectively. RESULTS: The two cases were 78 and 75 years old
      respectively. Both were complicated with many medical conditions. One case
      suffered from stage II cancer in the gastric body and stage IB rectal cancer, and
      the other suffered from stage IIIA gastric cancer and stage IB rectal cancer.
      Both cases had received laparoscopy-assisted combined radical resection for
      synchronous rectal and gastric cancer, with 5 cm of incision. The operative time
      was 260 and 255 min and the intraoperative bleeding was 60 and 80 ml
      respectively. No complication occurred intraoperatively. Time to resume oral
      intake was 4 and 5 days and length of postoperative hospital stay was 13 and 14
      days respectively. No postoperative complication occurred. The patients were
      followed up for 13 and 12 months and no postoperative recurrence or metastasis
      was noticed. CONCLUSION: Laparoscopy-assisted combined radical resection for
      elderly synchronous rectal and gastric cancer is safe and feasible when performed
      by surgeons with plentiful experience in laparoscopic technology, and associated
      with less injury and faster recovery.

PMID- 22368023
TI  - [Laparoscopy-assisted radical gastrectomy with D2 lymph node dissection for
      gastric cancer in the elderly].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopy-assisted
      radical gastrectomy with D2 lymph node (LN) dissection for elderly patients with
      gastric cancer. METHODS: From January 2007 to December 2009, 255 gastric cancer
      patients aged over 65 years underwent D2 LN dissection. Of these, 116 patients
      underwent laparoscopy-assisted radical gastrectomy (LAG group), while 139
      patients underwent conventional open gastrectomy (OG group). The recovery and
      complication rate were compared between the two groups. Risk factors associated
      with postoperative complications were investigated by univariate and multivariate
      analyses. RESULTS: Compared to the OG group, the mean blood loss and number of
      patients who required blood transfusion were less, and the time to first flatus,
      the time to resume soft diet, and postoperative hospital stay were shorter in the
      LAG group (all P<0.01). However, the operation time and the mean number of LN
      retrieval were not significantly different between the two groups (both P>0.05).
      The postoperative morbidity in the LAG group was 15.5% (18/116), lower than that
      in OG group [28.1% (39/139), P<0.05]. Logistic regression analysis revealed that
      there were three significant factors associated with postoperative complications
      such as laparoscopy-assisted gastrectomy (P<0.05), operation time (P<0.01), and
      preoperative comorbidity (P<0.01). Operation time (P<0.05) and preoperative
      comorbidity (P<0.01) were independent risk factors for complication in
      laparoscopy-assisted radical gastrectomy of elderly patients. The mean survival
      time of LAG and OG were 23.0 months and 22.5 months, respectively, and the
      difference was not statistically significant (P>0.05). CONCLUSIONS: Laparoscopy
      assisted radical gastrectomy with D2 LN dissection is oncologically compatible
      with open gastrectomy in elderly patients with gastric cancer less invasive.
      Operation time and preoperative comorbidity are independent risk factors for
      complication in laparoscopy-assisted radical gastrectomy of elderly patients.

PMID- 22368024
TI  - [Clinical analysis of 200 patients with primary gastric lymphoma].
AB  - OBJECTIVE: To study the clinical diagnosis, treatment and prognosis of primary
      gastric lymphoma (PGL). METHODS: Clinical data of 200 patients with PGL who were
      treated at the Tianjin Cancer Hospital were retrospectively reviewed. RESULTS:
      There were 110 males and 90 females. The age ranged between 19 and 80 (median,
      54) years old. Symptoms or laboratory examinations were not specific. Before the
      treatment, 130 cases were diagnosed correctly, and the remaining 70 were
      misdiagnosed as gastric cancer (n=59), gastric ulcer (n=5) and chronic gastritis
      (n=6). Twenty-four cases received chemotherapy alone, 29 cases surgery alone, 132
      cases underwent surgery plus chemotherapy, and 15 were not treated. The 200 cases
      all received follow-up ranging from 1 to 246 months (median, 26 months). The 1,
      3, 5, and 10-year survival rates were 65.0%, 57.5%, 56.2%, and 55.0%. Univariate
      analysis and multivariate analysis showed that emaciation (P<0.01), tumor
      location (P<0.01), treatment modality (P<0.01), histological type (P<0.05), and
      tumor staging (P<0.05) were independent factors of survival in patients with PGL.
      CONCLUSIONS: The misdiagnosis of PGL is very frequent. The treatment of choice
      should be comprehensive therapy based on surgery.

PMID- 22368025
TI  - [Clinical value of serum CEA, CA19-9, CA72-4 and CA242 in the diagnosis and
      prognosis of gastric cancer].
AB  - OBJECTIVE: To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4
      and CA242 in the diagnosis and prognosis of patients with gastric cancer.
      METHODS: One hundred and sixty gastric cancer patients who had received treatment
      from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed.
      Blood samples were taken from patients upon admission to the hospital, and CEA,
      CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to
      identify the clinical value of these tumor markers in diagnosis and prognosis.
      RESULTS: On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and
      CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of
      combined detection was 62.9%. CEA was more frequently positive in patients with
      lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients
      with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite
      analysis showed that CA72-4 was an independent prognostic factor (P=0.012).
      Patients with positive CA72-4 carried a 2.147-fold increased risk of death than
      those with negative CA72-4. Kaplan-Meier analysis showed that patients with
      positive CA19-9 or positive CA72-4 had worse survival than those with negative
      CA19-9 or CA72-4 (P=0.006, P=0.002). CONCLUSIONS: Tumor markers including CEA,
      CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in
      patients with gastric cancer. Combined detection of four tumor markers can
      increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9
      and CA72-4 are associated with the prognosis of patients with gastric cancer.

PMID- 22368026
TI  - [Expression of a protein peak(3144 m/z) in serum and its clinical significance in
      patients with gastric cancer].
AB  - OBJECTIVE: To investigate the expression of protein peak (3144 m/z) in serum and
      of its association with clinical pathological characteristics and prognosis in
      patients with gastric cancer. METHODS: Three hundred and twenty seven
      pathologically confirmed gastric cancer patients were recruited from February
      2006 to October 2008 in the Zhejiang Cancer Hospital. SELDI-TOF-MS was employed
      to detect the expression of protein peak (3144 m/z) in preoperative serum.
      RESULTS: The positive rate of 3144 m/z protein peak was 33.9% (111/327),
      significantly higher than that of CEA (21.1%,69/327), and the difference was
      statistically significant (P<0.01). The positive rate of combined detection of
      protein peak (3144 m/z)and CEA was 45.6% (149/327). The expression of protein
      peak (3144 m/z) was associated with clinical staging (P<0.01), nervous invasion
      (P<0.01), tumor size (P<0.01), vascular invasion (P<0.05), lymph node metastasis
      (P<0.05), expression of CEA (P<0.05), and depth of infiltration (P<0.05).
      Significant difference was observed in 3-year survival rate between the patients
      with protein peak and patients without protein peak (44.7% vs. 64.4%, P<0.01).
      However, 3144 m/z protein peak was not an independent prognostic factor on
      multivariate Cox regression analysis (P=0.057). CONCLUSION: Protein peak (3144
      m/z) may be used as a diagnostic or prognostic marker of gastric cancer.

PMID- 22368027
TI  - [Interaction of SerpinB5 and MAFbx in gastric cancer cell and its action site].
AB  - OBJECTIVE: To explore the interaction between SerpinB5 and MAFbx in gastric
      cancer cell and to identify the interaction sites. METHODS: The interaction
      between SerpinB5 and MAFbx was screened and validated by yeast two-hybrid
      screening and co-immunoprecipitation. The expression of MAFbx was analyzed after
      SerpinB5 expression being modified by RNA interference and pGBKT7-SerpinB5
      transfection. The impact of SerpinB5 on the expression of MAFbx was studied in
      gastric cancer cell line SUN-16. A model of MAFbx was constructed by homology
      modeling. The related residues for interaction were analyzed by Autodock4.0.
      RESULTS: The interaction between SerpinB5 and MAFbx was validated. The expression
      of MAFbx changed along with SerpinB5 expression. Amino acids including PRO261,
      ASN361, and LYS362 were key residue in the interaction of SerpinB5 and MAFbx.
      CONCLUSION: SerpinB5 interacts with MAFbx in gastric cancer cell. Amino acids
      including PRO261, ASN361, and LYS362 are potential binding sites.

PMID- 22368028
TI  - [Sorting of CD133(+) subset cells in human gastric cancer and the identification
      of their tumor initiating cell-like properties].
AB  - OBJECTIVE: To sort CD133(+) subset cells in human gastric cancer (GC) and to
      identify their tumor initiating cell-like properties. METHODS: The tissues of GC
      and normal tissues adjacent to GC were obtained from 50 patients. Samples were
      stained for CD133 by immunohistochemistry. Likewise, assessments of CD133 were
      undertaken by Western blot. Flow cytometry was used to determine the proportion
      of CD133(+) cells in four GC cell lines therein the KATO-III was sorted by
      magnetic activated cell sorting (MACS) method. The growing characteristics and
      the tumorigenic ability of CD133(+) cells were evaluated in vitro and in vivo.
      Meanwhile, the growth of single cells in suspension culture was observed and
      expression of stem cell-specific marker were determined using reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression of
      CD133 was demonstrated on the cell membranes in the mucosa and submucosa of
      primary GC, which were higher than those in the normal gastric tissues adjacent
      to cancer (P<0.05). Four GC cell lines including KATO-III, SGC-7901, AGS and MKN
      45 were found to contain (28 +/- 2)%, (17 +/- 2)%, (6 +/- 2)%, and (4 +/- 2)% of
      CD133(+) cells respectively. In addition, the purity of CD133(+) cells isolated
      from KATO-III by MACS was (91 +/- 3)% and up to(95 +/- 2)% after 1-week culture.
      CCK-8 detection showed that population doubling time of the CD133(+) cells was
      (21 +/- 3)h, significantly shorter than that of the CD133(-) cells[(40 +/- 8)h,
      P<0.05]. Notably, there was a remarkable difference of tumor formation rate
      between CD133(+) cells (100%), non-sorted cells (80%), and CD133(-) cells(0). The
      average mass and volume of tumor in group of CD133(+) cells was larger and
      heavier than those in non-sorted cells (P<0.05, P<0.05). Furthermore, the single
      cell proliferated well, formed the big sphere and semi-quantitative RT-PCR showed
      expression of stem cell markers such as Oct-4, Nanog, Sox-2, Musashi-1 and EGFR.
      CONCLUSIONS: CD133 protein expression in primary lesions is higher than those in
      the normal gastric tissues. CD133(+) subset cells can be isolated, purified, and
      amplified in human GC, and possess some properties including the ability of self
      renewal, proliferation, and higher tumorigenic ability in vivo and can express
      some stem cell markers.

PMID- 22368029
TI  - [Impacts of Bevacizumab on vascular endothelial growth factor and Sp1 expression
      in gastric cancer xenografts].
AB  - OBJECTIVE: To evaluate the effects of Bevacizumab on the tumor growth,
      proliferation and apoptosis of gastric cancer xenograft, and the impacts on the
      VEGF and Sp1 expression. METHODS: Gastric cancer xenografts in nude mice were
      established using SGC-7901 gastric cancer cell line. The nude mice were randomly
      divided into two groups, Bevacizumab treatment group and PBS group. The tumor
      sizes were measured for tumor growth curve. The proliferation and angiogenesis
      were evaluated by immunohistochemistry (IHC) staining of Ki67 and CD34. TUNEL
      assay was used for apoptosis evaluation. The expression of VEGF and Sp1 in tumor
      cells were detected by IHC and Western blot. RESULTS: Compared to the PBS group,
      the tumor growth decreased significantly (P<0.05), the proliferation of tumor
      cells and angiogenesis decreased, and apoptosis index increased significantly
      [(5.3 +/- 1.8)% vs. (16.7 +/- 6.7)%, P<0.01] in Bevacizumab group. The results of
      IHC and Western blot demonstrated that the expression of VEGF and the microvessel
      density (MVD) was decreased (4.0 +/- 1.0 vs. 16.3 +/- 1.5, P<0.001) in
      Bevacizumab treatment group. No obvious changes of Sp1 expression were observed
      in Bevacizumab treatment group. CONCLUSIONS: Bevacizumab can inhibit the growth
      of gastric cancer xenografts in nude mice, decrease the VEGF expression and MVD.
      However, the compensatory up-regulation of transcription factor Sp1 is not
      affected by Bevacizumab.

PMID- 22368030
TI  - [Clinical research progression in chemoradiation therapy for resectable gastric
      cancer].
AB  - In recent years, based on the phase III clinical study, postoperative
      chemoradiation, perioperative chemotherapy with ECF regimen and postoperative
      adjuvant chemotherapy with oral S-1 have become the standard adjuvant treatment
      of resectable gastric adenocarcinoma in the United States, Europe, and Japan,
      respectively. Since the Southwest Oncology Group in 2001 reported a large phase
      III randomized clinical trial INT0116, adjuvant chemoradiotherapy has become a
      standard treatment for gastric adenocarcinoma. With the rapid development of
      chemoradiotherapy technique, clinical researches for using operation combined
      with chemoradiotherapy to treat gastric adenocarcinoma emerged one after another,
      including adjuvant postoperative chemoradiation, preoperative chemoradiation, and
      chemoradiation combined with intraoperative radiotherapy and so on. This review
      will summarize the recent treatment protocol using chemoradiotherapy for
      resectable gastric adenocarcinoma, and comprehensively evaluate the clinical
      value and significance of chemoradiotherapy for resectable gastric
      adenocarcinoma.

PMID- 22368031
TI  - [Assessment of lymph node metastasis in gastric cancer: status quo, recent
      advances and new perspectives].
AB  - The precondition of accurate gastric cancer surgery is precise assessment of
      lymph node metastasis. To date, no imaging modality achieves both high
      sensitivity and high specificity in detecting lymph node metastasis in gastric
      cancer. Intraoperative sentinel node tracing and biopsy are the most popular
      method to identify the localization of tumor cell, but is limited to early
      gastric cancer. Nano-composite materials, designed for tumor imaging and tracing,
      show us a newly emerging domain for tumor detection in gastric cancer. The
      function of these nano-composite materials to detect lymph node metastasis in
      gastric cancer relies on the effective backflow of lymph system. However, the
      lymph vessels can be obstructed by tumor cells in advanced gastric cancer, which
      may restrain the application of these nanoparticles. Therefore, more methods to
      detect lymph node metastasis in gastric cancer should be explored. This review
      summarizes the characteristic of the targeted nanosphere. Based on the reported
      studies, a novel idea is conceived that targeted multifunctional nanosphere may
      be a potential method to achieve precise assessment of lymph node metastasis in
      gastric cancer.

PMID- 22368032
TI  - Night shift work characteristics and 6-sulfatoxymelatonin (MT6s) in rotating
      night shift nurses and midwives.
AB  - OBJECTIVES: Synthesis of melatonin follows a circadian cycle, with high melatonin
      levels during the night and low levels during the day. Light exposure at night
      has been hypothesised as one of potential mechanisms of breast carcinogenesis in
      the night shift workers through inhibition of melatonin synthesis. The aim of the
      study was to examine a number of determinants for night shift work in relation to
      6-sulfatoxymelatonin (MT6s), primary melatonin metabolite. METHODS: The cross
      sectional study included 354 nurses and midwives (aged 40-60 years) currently
      working on rotating night shifts and 370 working days only. Data from
      questionnaires and 1-week diaries were used to characterise current job and total
      occupational history. Associations between rotating night shift work
      characteristics and MT6s (creatinine adjusted) in spot morning urine were tested
      in multiple linear regression models. RESULTS: No significant differences were
      found for MT6s concentrations between women currently working on rotating night
      shifts and those working only day shifts (means 47.2 vs 45.7 ng/mg Cr,
      respectively). The adjusted means among rotating night shift nurses and midwives
      varied depending on the department of employment, from 35.1 ng/mg Cr in
      neonatology to 68.2 ng/mg Cr in the orthopaedics department. Women working eight
      or more night shifts per month had significantly lower MT6s levels than those
      having fewer night shifts per month (37.9 vs 47.4 ng/mg Cr, respectively). Total
      night shift work history was not associated with MT6s. CONCLUSIONS: The results
      of this study indicate that working eight or more night shifts per month may
      disrupt the synthesis of melatonin.

PMID- 22368033
TI  - A fascinating journey into history: exploration of the world of isonitriles en
      route to complex amides.
AB  - We describe herein our recent explorations in the field of isonitrile chemistry.
      An array of broadly useful coupling methodologies has been developed for the
      formation of peptidyl and glycopeptidyl amide bonds. We further describe the
      application of these methods to the syntheses of complex systems, including the
      cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles.

PMID- 22368034
TI  - Brief screening for mild cognitive impairment: validation of the Brazilian
      version of the Montreal cognitive assessment.
AB  - BACKGROUND: The Montreal Cognitive Assessment (MoCA) is a brief cognitive
      schedule that has been developed for the screening of patients with Mild
      Cognitive Impairment (MCI). MCI is recognized as a high-risk state for
      Alzheimer's disease. The aim of the present study is to examine the reliability
      and validity of the Brazilian version of the MoCA test (MoCA-BR) in a sample of
      older individuals with at least 4 years of education. METHODS: The MoCA-BR was
      administered to 112 older adults who were classified into three diagnostic groups
      according to their cognitive state (Alzheimer's disease, n = 28; MCI, n = 43;
      normal controls, n = 41). This procedure was based on clinical and
      neuropsychological data. The performance in the MoCA-BR was compared with the
      Mini-mental state examination (MMSE) and the Cambridge Cognitive Examination.
      Diagnostic accuracy was examined with the receiver operating characteristic (ROC)
      curve analyses. RESULTS: Cronbach's alpha for the MoCA-BR was 0.75. Temporal
      stability (retesting after 3 months) using intraclass correlation coefficient was
      0.75 (p < 0.001). The sensitivity and specificity of the MoCA-BR for MCI were 81%
      and 77%, respectively, with a cut-off score of 25 points. The area under the ROC
      curve for predicting MCI was 0.82 +/- 0.06. CONCLUSIONS: The present results
      indicate that the MoCA-BR maintains its core diagnostic properties rendering it a
      valid and reliable tool for the screening of MCI among older individuals with at
      least 4 years of education.

PMID- 22368035
TI  - Mnemonic strategy training partially restores hippocampal activity in patients
      with mild cognitive impairment.
AB  - Learning and memory deficits typify patients with mild cognitive impairment (MCI)
      and are generally attributed to medial temporal lobe dysfunction. Although the
      hippocampus is perhaps the most commonly studied neuroanatomical structure in
      these patients, there have been few attempts to identify rehabilitative
      interventions that facilitate its functioning. Here, we present results from a
      randomized, controlled, single-blind study in which patients with MCI and healthy
      elderly controls (HEC) were randomized to either three sessions of mnemonic
      strategy training (MS) or a matched-exposure control group (XP). All participants
      underwent pre- and posttraining fMRI scanning as they encoded and retrieved
      object-location associations. For the current report, fMRI analyses were
      restricted to the hippocampus, as defined anatomically. Before training, MCI
      patients showed reduced hippocampal activity during both encoding and retrieval,
      relative to HEC. Following training, the MCI MS group demonstrated increased
      activity during both encoding and retrieval. There were significant differences
      between the MCI MS and MCI XP groups during retrieval, especially within the
      right hippocampus. Thus, MS facilitated hippocampal functioning in a partially
      restorative manner. We conclude that cognitive rehabilitation techniques may help
      mitigate hippocampal dysfunction in MCI patients.

PMID- 22368037
TI  - Direct amide coupling of non-activated carboxylic acids and amines catalysed by
      zirconium(IV) chloride.

PMID- 22368038
TI  - The cortisol response to hypobaric hypoxia at rest and post-exercise.
AB  - High altitude exposure normally leads to a marked natriuresis and diuresis. Acute
      mountain sickness is often associated with fluid retention, to which an elevated
      cortisol may contribute. Most investigators report a rise in resting cortisol
      with ascent, but little data exist regarding the cortisol response to a day
      trekking. We therefore measured salivary cortisol during ascent to > 5000 m in a
      cohort of between 42-45 subjects following a 6-h trek (samples taken between
      15:30-16:30 h) and between 15-20 subjects at rest (morning samples taken between
      08:00-09:00 h). Morning resting cortisol [nmol/l, mean+/-sd, (range)] was 5.5+/
      2.9 (2.13-13.61) at 1300 m; 4.7+/-6.8 (1.4-27.02) at 3400 m, and significantly
      (p=0.002) rose between 4270 m [3.5+/-2.1 (1.4-8.34)] and 5150 m [14.5+/-30.3 (1.9
      123.1)]. Post-exercise cortisol [nmol/l, mean+/-sd, (range)] dropped between 3400
      m [7+/-6 (1.5-33.3)] and 4270 m [4.2+/-4.8 (1.4-29.5)] (p=0.001) followed by a
      significant rise in post-exercise cortisol between 4270 m [4.2+/-4.8 (1.4-29.5)]
      and 5 150 m [9.2+/-10.2 (1.4-61.3)] (p<0.001). There were no significant
      associations between severity of acute mountain sickness and cortisol levels.
      There was a significant though weak correlation between cortisol post-exercise at
      5150 m and oxygen saturation at 5150 m (rho= - 0.451, p=0.004). In conclusion,
      this is the largest cohort to have their resting and post-exercise cortisol
      levels ascertained at high altitude. We confirm the previous findings of an
      elevated resting morning cortisol at > 5000 m, but present the novel finding that
      the cortisol response to a day trekking at HA appears suppressed at 4270 m.

PMID- 22368036
TI  - Anesthetics isoflurane and desflurane differently affect mitochondrial function,
      learning, and memory.
AB  - OBJECTIVE: There are approximately 8.5 million Alzheimer disease (AD) patients
      who need anesthesia and surgery care every year. The inhalation anesthetic
      isoflurane, but not desflurane, has been shown to induce caspase activation and
      apoptosis, which are part of AD neuropathogenesis, through the mitochondria
      dependent apoptosis pathway. However, the in vivo relevance, underlying
      mechanisms, and functional consequences of these findings remain largely to be
      determined. METHODS: We therefore set out to assess the effects of isoflurane and
      desflurane on mitochondrial function, cytotoxicity, learning, and memory using
      flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry,
      and the fear conditioning test. RESULTS: Here we show that isoflurane, but not
      desflurane, induces opening of mitochondrial permeability transition pore (mPTP),
      increase in levels of reactive oxygen species, reduction in levels of
      mitochondrial membrane potential and adenosine-5'-triphosphate, activation of
      caspase 3, and impairment of learning and memory in cultured cells, mouse
      hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a
      blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3
      activation, and impairment of learning and memory. Finally, isoflurane may induce
      the opening of mPTP via increasing levels of reactive oxygen species.
      INTERPRETATION: These findings suggest that desflurane could be a safer
      anesthetic for AD patients as compared to isoflurane, and elucidate the potential
      mitochondria-associated underlying mechanisms, and therefore have implications
      for use of anesthetics in AD patients, pending human study confirmation.

PMID- 22368039
TI  - Management of dysphonic patients by otolaryngologists.
AB  - OBJECTIVE: To investigate common treatment approaches of general
      otolaryngologists for adult dysphonic patients without obvious laryngeal anatomic
      abnormalities. STUDY DESIGN: Cross-sectional survey. SETTING: General
      otolaryngology community. SUBJECTS AND METHODS: One thousand randomly chosen
      American Academy of Otolaryngology-Head and Neck Surgery general
      otolaryngologists were mailed a survey. RESULTS: The response rate was 27.8%.
      Mean years in practice was 19.5. The most common treatments were proton pump
      inhibitor (PPI), referral to speech pathology, and stroboscopy. Muscle tension
      dysphonia, vocal fold nodules, and dysphonia of uncertain etiology were the most
      common reasons for voice therapy referral. Various forms of supraglottic
      compression and tender extralaryngeal muscles were identified as findings of
      muscle tension dysphonia. Response to once-daily PPI, laryngeal signs, and throat
      symptoms were the most common determinants for laryngopharyngeal reflux. When
      patients failed initial treatment, 58.2% refer for voice therapy, 46.9% obtain
      stroboscopy, and 33.3% extend or increase duration of PPI treatment. CONCLUSIONS:
      Varied treatment approaches to adult dysphonic patients were identified. How
      practice patterns vary from best practice guidelines, affect patient outcome, and
      influence health care costs needs examination.

PMID- 22368040
TI  - Differences in head and neck cancer risk perception between smoking and
      nonsmoking NASCAR attendees.
AB  - OBJECTIVE: Although research has documented a difference in cancer risk
      perception between smokers and nonsmokers, this has not been specifically
      documented for head and neck cancer. The aim of this study was to determine
      differences in risk perception for head and neck cancer between smokers and
      nonsmokers in an at-risk population. STUDY DESIGN: A cross-sectional survey was
      administered. SETTING: Community-based head and neck cancer screenings. SUBJECTS
      AND METHODS: Participants completed a 28-item questionnaire assessing
      sociodemographic information, smoking status, and risk perception of head and
      neck cancer. RESULTS: In total, 507 participants completed the questionnaire.
      Multivariate analysis of variance (MANCOVA) using dependent variables related to
      risk perception of head and neck cancer evidenced a significant main effect that
      smokers (mean [SD], 1.10 [0.07]) worried about head and neck cancer significantly
      more than nonsmokers (0.64 [0.06]), F(1, 459) = 26.97, P < .001, eta(2) = .06,
      and nonsmokers (2.70 [0.05]) believed head and neck cancer was significantly more
      dangerous than did smokers (2.53 [0.06]), F(1, 459) = 5.90, P = .015, eta(2) =
      .01. CONCLUSION: Findings indicated differences in perception of risk for head
      and neck cancer between smokers and nonsmokers. By gaining a better understanding
      of the psychosocial factors related to perceived risk of head and neck cancer,
      otolaryngologists and health care providers may better tailor interventions aimed
      at increasing awareness of cancer risk and promoting cessation.

PMID- 22368041
TI  - Feasibility of dual wireless esophageal pH monitoring: randomized blinded sham
      controlled trial.
AB  - OBJECTIVE: Wireless pH monitoring is currently employed in the distal esophagus.
      There are no controlled studies on the feasibility/safety of proximal esophageal
      wireless pH capsule placement. We tested the hypothesis that there will be no
      difference in patient perception of a more proximally placed pH capsule. STUDY
      DESIGN: Randomized single-blinded sham-controlled trial. SETTING: Tertiary care
      center. SUBJECTS AND METHODS: All patients had a wireless pH capsule positioned 6
      cm proximal to the gastroesophageal junction. They were randomized into
      intervention or sham groups after distal capsule placement. The delivery
      introducer was positioned 10 cm proximal to the distal esophageal capsule, and a
      second capsule was either deployed (intervention) or not (sham) based on group
      allocation. Patients were blinded to group assignment. Modified Edmonton Score
      was used to assess for chest pain, dysphagia, and odynophagia. The primary
      endpoints were (1) required endoscopic removal because of discomfort and (2)
      change in chest pain scores, controlling for baseline pain. RESULTS: Patients
      were randomized to either the intervention, proximal esophageal capsule (n = 11),
      or sham (n = 11). Patients with proximal pH probes had higher odds of having
      their chest pain (odds ratio [OR], 8.44; 95% confidence interval [CI], 1.35-52.6;
      P = .02), odynophagia (OR, 49.5; 95% CI, 4.70-520; P = .001), and dysphagia (OR,
      14.3; 95% CI, 2.12-96.6; P = .006) exacerbated. Two (2/11; 18%) proximally
      deployed probes required endoscopic removal because of patient intolerance or
      discomfort. CONCLUSION: A proximal esophageal wireless pH monitor placement is
      feasible but results in increased chest pain, odynophagia, and dysphagia that can
      be severe enough to require endoscopic removal. These limitations preclude its
      potential clinical benefit.

PMID- 22368042
TI  - Liposuction for the management of submental lymphedema in the head and neck
      cancer patient.

PMID- 22368043
TI  - Bone-anchored implantation for single-sided deafness in patients with less than
      profound hearing loss.
AB  - OBJECTIVE: The benefit of bone-anchored implantation (BAI) for the treatment of
      single-sided deafness (SSD) is well established. In this study, the authors
      sought to evaluate objective hearing outcomes and subjective benefits in patients
      undergoing BAI for SSD with residual hearing in the implanted ear. STUDY DESIGN:
      Case series with chart review. SETTING: Academic tertiary referral center.
      SUBJECTS AND METHODS: All adult, English-speaking patients undergoing BAI for SSD
      from 2004 to 2010 were included. Patients were divided into 2 groups: (1)
      residual hearing in the affected ear (<= 90 db hearing level [HL] pure-tone
      average [PTA]) and (2) profound hearing loss in the affected ear (>90 dB HL PTA).
      Patients underwent pre- and postoperative objective hearing outcomes testing
      including speech-in-noise and monosyllabic word tests. Subjective outcomes were
      measured pre- and postoperatively using the Glasgow Hearing Aid Benefit Profile
      (GHABP). RESULTS: Patients in both groups showed significant improvement in all
      objective hearing measures following implantation (P < .0001), and there were no
      significant differences in objective hearing outcomes between groups. Subjective
      benefits from BAI varied across patients according to GHABP results, but patients
      with residual hearing in the affected ear trended toward improved satisfaction
      with their device postoperatively. CONCLUSION: Individuals with SSD and residual
      cochlear reserve can be successfully implanted with BAI, achieving significant
      improvements in objective hearing measures. Postoperative improvements do not
      seem to correlate with the preoperative audiometric testing scores. Although
      subjective benefit varies across patients, BAI is clearly a viable rehabilitation
      option for patients with SSD and less than profound hearing loss.

PMID- 22368044
TI  - Syndrome of inappropriate antidiuretic hormone secretion in patients with
      olfactory neuroblastoma.
AB  - OBJECTIVE: The syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      has been reported as a paraneoplastic syndrome in many different types of
      malignancies. Several case reports of SIADH have been reported in patients with
      olfactory neuroblastoma (ONB), but the exact incidence is unknown. The purpose of
      this study was to review our experience with olfactory neuroblastoma and to
      identify all patients who had a history of SIADH prior to the diagnosis of ONB.
      STUDY DESIGN: Case series and chart review. SETTING: Tertiary care university
      affiliated medical center. SUBJECTS AND METHODS: A total of 21 patients presented
      to our institution with ONB between 1997 and 2009. All records were reviewed for
      a history of preoperative hyponatremia or SIADH. RESULTS: Three patients were
      identified who had a history of SIADH prior to the diagnosis of ONB.
      Immunohistochemical staining of the tumor specimens from the 3 patients with
      SIADH was positive for arginine vasopressin. SIADH resolved in all 3 patients
      after successful treatment of ONB. CONCLUSION: Although uncommon, SIADH can be
      the presenting symptom of ONB and should be considered during the workup for
      idiopathic SIADH.

PMID- 22368045
TI  - Characterization of cerium oxide nanoparticles-part 1: size measurements.
AB  - The present study gives an overview of some of the major aspects for
      consideration in the characterization of nanomaterials (NMs). Part 1 focuses on
      the measurement of particle size and size-related parameters using several
      analytical techniques such as transmission electron microscopy, atomic force
      microscopy, dynamic light scattering, X-ray diffraction, and Brunauer, Emmett,
      and Teller surface area measurements as applied to commercially available cerium
      oxide nanoparticles (NPs) and microparticles (MPs). Part 2 (see companion paper)
      considers nonsize-related characterization and analysis. The results are
      discussed in relation to the nature of the sample and preparation, and the
      analytical principles, limitations, and advantages of each technique. Accurate
      information on the particle size of the different fractions of a sample can be
      obtained by using a combination of different types of microscopy, spectroscopy,
      separation, and other techniques; this should inform ecotoxicological and
      environmental studies. The good agreement between the measured primary particle
      size of the NPs (~15 nm) by atomic force microscopy, transmission electron
      microscopy, X-ray diffraction, and Brunauer, Emmett, and Teller suggests that the
      primary particles are formed of semispherical single crystals. For MPs, all
      measurements agree that they are large particles in the range above the NPs (100
      nm), with some difference between the measured sizes, possibly as a result of
      polydispersity effects. Additionally, our findings suggest that atomic force
      microscopy and transmission electron microscopy prepared by centrifugation
      methods provide consistent data at low concentrations when dynamic light
      scattering fails.

PMID- 22368046
TI  - Graphene-supported hemin as a highly active biomimetic oxidation catalyst.
AB  - Well supported: stable hemin-graphene conjugates formed by immobilization of
      monomeric hemin on graphene, showed excellent catalytic activity, more than 10
      times better than that of the recently developed hemin-hydrogel system and 100
      times better than that of unsupported hemin. The catalysts also showed excellent
      binding affinities and catalytic efficiencies approaching that of natural
      enzymes.

PMID- 22368047
TI  - Voltage dependence of subthreshold resonance frequency in layer II of medial
      entorhinal cortex.
AB  - The resonance properties of individual neurons in entorhinal cortex (EC) may
      contribute to their functional properties in awake, behaving rats. Models propose
      that entorhinal grid cells could arise from shifts in the intrinsic frequency of
      neurons caused by changes in membrane potential owing to depolarizing input from
      neurons coding velocity. To test for potential changes in intrinsic frequency, we
      measured the resonance properties of neurons at different membrane potentials in
      neurons in medial and lateral EC. In medial entorhinal neurons, the resonant
      frequency of individual neurons decreased in a linear manner as the membrane
      potential was depolarized between -70 and -55 mV. At more hyperpolarized membrane
      potentials, cells asymptotically approached a maximum resonance frequency.
      Consistent with the previous studies, near resting potential, the cells of the
      medial EC possessed a decreasing gradient of resonance frequency along the dorsal
      to ventral axis, and cells of the lateral EC lacked resonant properties,
      regardless of membrane potential or position along the medial to lateral axis
      within lateral EC. Application of 10 MUM ZD7288, the H-channel blocker, abolished
      all resonant properties in MEC cells, and resulted in physiological properties
      very similar to lateral EC cells. These results on resonant properties show a
      clear change in frequency response with depolarization that could contribute to
      the generation of grid cell firing properties in the medial EC.

PMID- 22368048
TI  - Effects of high-pressure argon and nitrogen treatments on respiration, browning
      and antioxidant potential of minimally processed pineapples during shelf life.
AB  - BACKGROUND: High-pressure (HP) inert gas processing causes inert gas and water
      molecules to form clathrate hydrates that restrict intracellular water activity
      and enzymatic reactions. This technique can be used to preserve fruits and
      vegetables. In this study, minimally processed (MP) pineapples were treated with
      HP (~10 MPa) argon (Ar) and nitrogen (N) for 20 min. The effects of these
      treatments on respiration, browning and antioxidant potential of MP pineapples
      were investigated after cutting and during 20 days of storage at 4  degrees C.
      RESULTS: Lower respiration rate and ethylene production were found in HP Ar- and
      HP N-treated samples compared with control samples. HP Ar and HP N treatments
      effectively reduced browning and loss of total phenols and ascorbic acid and
      maintained antioxidant capacity of MP pineapples. They did not cause a
      significant decline in tissue firmness or increase in juice leakage. HP Ar
      treatments had greater effects than HP N treatments on reduction of respiration
      rate and ethylene production and maintenance of phenolic compounds and DPPH(*)
      and ABTS(*+) radical-scavenging activities. CONCLUSION: Both HP Ar and HP N
      processing had beneficial effects on MP pineapples throughout 20 days of storage
      at 4  degrees C.

PMID- 22368049
TI  - Synergistic effects of central nervous system-directed gene therapy and bone
      marrow transplantation in the murine model of infantile neuronal ceroid
      lipofuscinosis.
AB  - OBJECTIVE: Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited
      childhood neurodegenerative disorder caused by the loss of palmitoyl protein
      thioesterase-1 (PPT1) activity. Affected children suffer from blindness,
      epilepsy, motor dysfunction, cognitive decline, and premature death. The Ppt1(-/
      ) mouse shares the histological and clinical features of INCL. Previous single
      therapy approaches using small molecule drugs, gene therapy, or neuronal stem
      cells resulted in partial histological correction, with minimal improvements in
      motor function or lifespan. Here, we combined central nervous system (CNS)
      directed adeno-associated virus (AAV)2/5-mediated gene therapy with bone marrow
      transplantation (BMT) in the INCL mouse. METHODS: At birth, Ppt1(-/-) and wild
      type mice were given either intracranial injections of AAV2/5-PPT1 or bone marrow
      transplantation, separately as well as in combination. To assess function, we
      measured rotorod performance monthly as well as lifespan. At terminal time
      points, we evaluated the therapeutic effects on several INCL-specific parameters,
      such as cortical thickness, autofluorescent accumulation, and glial activation.
      Finally, we determined levels of PPT1 enzyme activity and bone marrow engraftment
      in treated mice. RESULTS: AAV2/5-mediated gene therapy alone resulted in
      significant histological correction, improved motor function, and increased
      lifespan. Interestingly, the addition of BMT further increased the lifespan of
      treated mice and led to dramatic, sustained improvements in motor function. These
      data are truly striking, given that BMT alone is ineffective, yet it synergizes
      with CNS-directed gene therapy to dramatically increase efficacy and lifespan.
      INTERPRETATION: AAV2/5-mediated gene therapy in combination with BMT provides an
      unprecedented increase in lifespan as well as dramatic improvement on functional
      and histological parameters.

PMID- 22368050
TI  - Study on the noncovalent interactions of saikosaponins and cytochrome c by
      electrospray ionization mass spectrometry.
AB  - RATIONALE: The study of interactions between protein and pharmaceutical molecules
      including natural extracts has become of increasing interest in biological and
      biomedical research. An investigation of the interaction between saikosaponins
      and cytochrome c (Cyt c) by electrospray ionization mass spectrometry (ESI-MS) is
      described in this study. Saikosaponins are found in Bupleurum falcatum (a
      flowering plant), and they are glycosides that consist of saccharides and the
      sapogenins of triterpenoids. METHODS: Seven model molecules of saccharides and
      triterpenes, namely maltose (Mal II), maltotriose (Mal III), raffinose (Raf), and
      stachyose (Sta), glycyrrhetinic acid (Gly), ursolic acid (Urs) and oleanic acid
      (Ole), were chosen to perform a series of ESI-MS control experiments for the
      exploration of the interaction groups in saikosaponins with Cyt c. The
      dissociation constants of detected noncovalent complexes were determined by using
      a direct ESI-MS assay. RESULTS: We have observed in the ESI mass spectra the
      formation of Cyt c complexes with saikosaponins a and c, and these saccharides,
      with 1:1 and 1:2 stoichiometry. Our results showed that no complex ions of
      triterpenes and Cyt c were detected in the ESI-MS and similar Kd values were
      obtained for the Cyt c complexes of saikosaponins and saccharides. This
      demonstrates that the glycosyl moiety in the saikosaponins is the effective
      interaction group with Cyt c. We propose that saikosaponins and saccharides
      interact with Cyt c by hydrogen bonds. The binding affinity of these six ligands
      with Cyt c is shown to be in the order Ssa > Ssc > Raf, Mal III > Sta >= Mal II.
      CONCLUSIONS: The ESI-MS methodology presented in this study enables us to
      investigate the interactions of saikosaponins with Cyt c, and allows the direct
      determination of binding constants. These results could guide further research
      for providing insights into the structure-binding relationship of ligands with
      Cyt c.

PMID- 22368051
TI  - Molecular phylogenetics by direct comparison of tandem mass spectra.
AB  - RATIONALE: Molecular phylogenetics is the study of evolution and relatedness of
      organisms or genes. Mass spectrometry is used routinely for bacterial
      identification and has also been used for phylogenetic analysis, for instance
      from bone material. Unfortunately, only a small fraction of the acquired tandem
      mass spectra allow direct interpretation. METHODS: We describe a new algorithm
      and software for molecular phylogenetics using pairwise comparisons of tandem
      mass spectra from enzymatically digested proteins. The spectra need not be
      annotated and all acquired data is used in the analysis. To demonstrate the
      method, we analyzed tryptic digests of sera from four great apes and two other
      primates. RESULTS: The distribution of spectra dot products for thousands of
      tandem mass spectra collected from two samples provides a measure on the fraction
      of shared peptides between the two samples. When inverted, this becomes a
      distance metric. By pairwise comparison between species and averaging over four
      individuals per species, it was possible to reconstruct the unique correct
      phylogenetic tree for the great apes and other primates. CONCLUSIONS: The new
      method described here has several attractive features compared with existing
      methods, among them simplicity, the unbiased use of all acquired data rather than
      a small subset of spectra, and the potential use of heavily degraded proteins or
      proteins with a priori unknown modifications.

PMID- 22368052
TI  - Determination of levamisole in feeds by liquid chromatography coupled to
      electrospray mass spectrometry on an ion trap.
AB  - Test methods have to be developed by laboratories for official control to monitor
      possible misuse of veterinary drugs in animal productions, also through feeding
      stuff. A novel method for identification and quantification of levamisole in
      feeds by liquid chromatography coupled to electrospray mass spectrometry in an
      ion trap (LC/ESI-MS/MS) is herein described; after a single-step cleanup by
      liquid-liquid extraction from the feed and separation by reversed-phase liquid
      chromatography, levamisole was determined and unambiguously confirmed by tandem
      mass spectrometry, on the basis of two product ions. The method was in-house
      validated, according to the Regulation 882/2004/EC, evaluating trueness,
      repeatability, within-laboratory reproducibility, ruggedness, specificity, and
      the limit of quantification (LOQ). The method is reliable and specific for
      complete and complementary feeds for pigs, cattle, rabbits and poultry; very good
      mean recoveries (higher than 92 %) and precision (RSD values < 15.2%) were
      attained. The LOQ at 2.0 mg/kg was verified. Moreover, we describe how the method
      was developed to support Italian Police investigations regarding illegal
      treatments of pigs; in this case, since the drug(s) added to the feed were
      unknown, a preliminary untargeted analysis was performed by full scan mass
      spectrometry on an ion trap, from 50 up to 2000 m/z; the presence of levamisole
      was hypothesised, on the basis of the most abundant ion and its fragmentation
      pattern. Then, levamisole was unambiguously confirmed by the ion trap LC/ESI
      MS/MS method.

PMID- 22368053
TI  - Screening of glycoside isomers in P. scrophulariiflora using ionic liquid-based
      ultrasonic-assisted extraction and ultra-performance liquid
      chromatography/electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry.
AB  - A powerful ionic liquid-based ultrasonic-assisted extraction (ILUAE) method
      combined with ultra-performance liquid chromatography coupled to electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOFMS(n)
      ) was employed in the rapid simultaneous screening of iridoid glycosides,
      phenylethanoid glycosides, and cucurbitacin glycosides from P. scrophulariiflora.
      The ILUAE procedure was optimized over several ultrasonic parameters, including
      the ultrasonic power, concentration of the ionic liquid, and solid-liquid ratio.
      A comparison with conventional heat-reflux extraction and regular UAE
      demonstrated that the optimized approach yielded a high extraction efficiency
      (Picroside I, 2.84%; Picroside II, 3.57%; 6-O-E-feruloyl catalpol, 2.20%) within
      a short extraction time of 30 min. Negative ion mode ESI-QTOFMS(2) analysis of
      the fragmentation reactions of the [M-H](-) ions was conducted to characterize
      the diagnostic ions related to the glycosyl moieties, aglycone units, and the
      type and substituted position of the ester groups. Interestingly, the positional
      isomers of the iridoid glycosides could be easily discriminated based on the
      characteristic ions. A total of 15 glycosides, including three groups of iridoid
      glycoside isomers and two groups of phenylethanoid glycoside isomers, were
      conveniently identified within 13.5 min. Moreover, 6'-O-vanilloyl catalpol was
      identified in P. scrophulariiflora for the first time. The method developed here
      was further validated by measuring the recovery, correlation coefficient (R(2) ),
      and reproducibility (RSD, n = 5) of three iridoid glycosides: 89.60%-109.02%,
      0.9991-0.9998, and 0.93%-1.44%, respectively. This study demonstrated the
      capabilities of ILUAE combined with UPLC/ESI-QTOFMS(n) for the rapid screening of
      glycosides in P. scrophulariiflora. This method offers an approach to similar
      studies on other natural plants.

PMID- 22368054
TI  - Determination of glycation sites by tandem mass spectrometry in a synthetic
      lactose-bovine serum albumin conjugate, a vaccine model prepared by dialkyl
      squarate chemistry.
AB  - RATIONALE: Neoglycoconjugate vaccines synthesized by the squaric acid spacer
      method allow single point attachment of the carbohydrate antigen to the protein
      carrier. However, the localization of the carbohydrate antigen sites of
      conjugation on the protein carrier has been an elusive task difficult to achieve.
      METHOD: Covalent attachment of the lactose antigen to the bovine serum albumin
      (BSA) was prepared by the squaric acid method using a hapten:BSA ratio of 20:1.
      Different reaction times were used during the conjugation reaction and two
      different lactose-BSA glycoconjugate vaccines were obtained. The carbohydrate
      antigen hapten:BSA ratios of these lactose-BSA glycoconjugate vaccines were
      determined by MALDI-TOF/RTOF-MS and the glycation sites in the neoglycoconjugates
      were determined using nano-LC/ESI-QqTOF-MS/MS analysis of the trypsin and GluC V8
      digests of the conjugates. RESULTS: We have identified a total of 15 glycation
      sites located on the BSA lysine residues for the neoglycoconjugate vaccine formed
      with a hapten:BSA ratio of 5.1:1, However, the tryptic and GluC V8 digests of the
      hapten-BSA glycoconjugate with a hapten:BSA ratio of 19.0:1 allowed
      identification of 30 glycation sites located on the BSA. These last results seem
      to indicate that this conjugation results in formation of various glycoforms.
      CONCLUSIONS: It was observed that the number of identified glycation sites
      increased when the hapten:BSA ratio of glycoconjugate formation increased, and
      that the location of the glycation sites appears to be mainly on the outer
      surface of the BSA carrier molecule which is in line with the assumption that the
      sterically more accessible lysine residues, namely those located on the outer
      surface of the BSA, would be conjugated preferentially.

PMID- 22368055
TI  - Thermal decomposition of pyridoxine: an evolved gas analysis-ion attachment mass
      spectrometry study.
AB  - RATIONALE: Pyridoxine is an important vitamer in food and pharmaceutical
      products. Heat treatments applied during preparation or storage of the products
      cause the decomposition of pyridoxine. Identification and understanding of the
      degradation products of pyridoxine and studying its decomposition kinetics are
      essential in the preparation and preservation of pyridoxine-containing foods and
      pharmaceuticals. METHODS: Real-time, non-isothermal decomposition of pyridoxine
      was studied using evolved gas analysis-Li(+) ion attachment mass spectrometry
      (EGA-Li(+) IAMS). Arrhenius parameters for the thermal decomposition of
      pyridoxine were obtained via the total ion monitoring (TIM) curve. RESULTS: Most
      of the pyridoxine evaporated in molecular form, but the formation of pyridoxal
      and o-quinone methide, both biologically important species, was also observed
      from the solid-phase degradation of pyridoxine. The observation of o-quinone
      methide, a species possessing anticancer activity, was particularly noteworthy
      due to its chemical instability. The activation energy (E(a) ) for pyridoxine
      decomposition determined by EGA-IAMS was found to be 20.0 kcal mol(-1) , and the
      pre-exponential factor (A) was 5.7 * 10(9)  min(-1) . CONCLUSIONS: The calculated
      kinetic parameters are important for predicting the thermal stability of
      pyridoxine vitamer. The estimated lifetime (t(90%,25 degrees C) ) of 1.7 * 10(-2)
      years in nitrogen was also obtained from the EGA-IAMS experiment.

PMID- 22368056
TI  - Tandem mass spectrometry of electrosprayed polyhedral oligomeric silsesquioxane
      compounds with different substituents.
AB  - RATIONALE: Polyhedral oligomeric silsesquioxanes (POSSs), defined as [RSiO(3/2)
      ](n) with R designating an organic substituent, were considered here as models of
      highly cross-linked polysiloxanes, to be further used as references in tandem
      mass spectrometric characterization of plasma polymers of hexamethyldisiloxane,
      expected to be composed of organic polydimethylsiloxane (PDMS) and inorganic
      (SiO(x) ) silica-based parts. The collision-induced dissociation (CID) behavior
      of [RSiO(3/2) ](8) compounds was then studied as a function of the R substituent.
      METHODS: POSS compounds were produced in the gas phase as ammonium adducts and
      the product ions generated upon CID, amongst which was the protonated precursor,
      were accurately mass measured in an orthogonal acceleration time-of-flight mass
      analyzer. RESULTS: The presence of eight propylamine substituents was shown to
      induce sequential dehydration of the protonated precursor, ultimately leading to
      a complete unfolding of the POSS cage. Similar opening of the octahedron
      structure in the protonated molecule substituted with OSi(CH(3) )(3) , OSiH(CH(3)
      )(2) or OH (formed upon methanolysis of dimethylsiloxy substituents) was proposed
      to account for the product ions generated during their CID. Sequential charge
      remote transfers of a methyl group (and of H in the case of dimethylsiloxy
      substituents) from one substituent group to a neighboring one was shown to lead
      to a linear co-oligomeric chain composed of randomly distributed siloxy-based
      monomers. CONCLUSIONS: All the peaks observed in CID could be accounted for by
      applying dissociation reactions typically occurring in protonated polysiloxane
      like oligomers. The large number of product ions observed in MS/MS was found to
      result from the variety of possible structural rearrangements, producing numerous
      linear isomeric forms of the dissociating species.

PMID- 22368057
TI  - Isotopic values of the Amazon headwaters in Peru: comparison of the wet upper Rio
      Madre de Dios watershed with the dry Urubamba-Apurimac river system.
AB  - RATIONALE: The Amazon River is a huge network of long tributaries, and little is
      known about the headwaters. Here we present a study of one wet tropical Amazon
      forest side, and one dry and cold Atiplano plateau, originating from the same
      cordillera. The aim is to see how this difference affects the water
      characteristics. METHODS: Different kind of water (spring, lake, river, rainfall)
      were sampled to determine their stable isotopes ratios (oxygen 18/16 and hydrogen
      2/1) by continuous flow isotope ratio mass spectrometry (IRMS). These ratios
      coupled with chemical analysis enabled us to determine the origin of the water,
      the evaporation process and the water recycling over the Amazon plain forest and
      montane cloud forest. RESULTS: Our study shows that the water flowing in the
      upper Madre de Dios basin comes mainly from the foothill humid forest, with a
      characteristic water recycling process signature, and not from higher glacier
      melt. On the contrary, the water flowing in the Altiplano Rivers is mainly from
      glacier melts, with a high evaporation process. This snow and glacier are fed
      mainly by Atlantic moisture which transits over the large Amazon forest.
      CONCLUSIONS: The Atlantic moisture and its recycling over this huge tropical
      forest display a progressive isotopic gradient, as a function of distance from
      the ocean. At the level of the montane cloud forest and on the altiplano,
      respectively, additional water recycling and evaporation occur, but they are
      insignificant in the total water discharge.

PMID- 22368058
TI  - Inferring occurrence of growth checks in pike (Esox lucius) scales by using
      sequential isotopic analysis of otoliths.
AB  - RATIONALE: Sequential analysis of otolith oxygen isotope (delta(18) O(oto) )
      values was performed by classical mechanical microdrilling and dual inlet mass
      spectrometry to infer the timing of growth checks in pike (Esox lucius) scales
      from Lake Annecy (France). It indicated that the first check on scales occurs
      before the first winter of life of the fish. METHODS: Eleven fish caught in
      February and June 2008 were studied. Intra-individual isotopic profiles exhibit
      cyclic variations that are consistent with that of modeled delta(18) O(oto)
      values using variations in epilimnion temperature and otolith-specific isotope
      fractionation equations. The positions of growth checks on scales were compared
      with the periodic variations of delta(18) O(oto) values on otolith radii using an
      allometric relationship. RESULTS: All individuals presented at least one check
      deposited before the first winter. Deposition of some checks might be linked to a
      shift in fish diet or habitat or to catch-and-release induced stress.
      CONCLUSIONS: Although coupling between sequential analysis of delta(18) O(oto)
      values and observation of scale growth features has been shown to be useful,
      there are limitations in the methodology, especially for the growth-attenuated
      region of otoliths associated with older ages.

PMID- 22368059
TI  - Development of a liquid chromatographic method based on ultraviolet-visible and
      electrospray ionization mass spectrometric detection for the identification of
      nitrocatechols and related tracers in biomass burning atmospheric organic
      aerosol.
AB  - RATIONALE: Studying the chemical composition of biomass burning aerosol (BBA) is
      very important in order to assess their impact on the climate and the biosphere.
      In the present study, we focus on the characterization of some newly recognized
      biomass burning aerosol tracers including methyl nitrocatechols, nitroguaiacols
      and 4-nitrocatechol, but also on nitrophenols, methyl nitrophenols and
      nitrosalicylic acids, using liquid chromatography tandem mass spectrometry.
      METHODS: For the purpose of their separation and detection in atmospheric
      aerosol, a new chromatographic method was initially developed based on reversed
      phase chromatography coupled with ultraviolet/visible (UV/Vis) detection. The
      method was afterwards transferred to a liquid chromatography/electrospray
      ionization linear ion trap mass spectrometry (LC/ESI-LITMS) system in order to
      identify the targeted analytes in winter aerosol from the city of Maribor,
      Slovenia, using their chromatographic retention times and characteristic (-)ESI
      product ion (MS(2) ) spectra. RESULTS: The fragmentation patterns of analytes
      obtained with LITMS are presented. Additional nitro-aromatic compounds (m/z 168
      and 182) closely related to the targeted nitrocatechols and nitroguaiacols were
      detected in the aerosol. According to their MS(2) spectra these compounds could
      be attributed to methyl homologues of methyl nitrocatechols and nitroguaiacols.
      CONCLUSIONS: The proposed LC/MS method results in a better separation and
      specificity for the targeted analytes. Several nitro-aromatic compounds were
      detected in urban BBA. The LC/MS peak intensity of the newly detected methyl
      nitrocatechols and nitroguaiacols is comparable to that of the methyl
      nitrocatechols, which also qualifies them as suitable molecular tracers for
      secondary biomass burning aerosol.

PMID- 22368060
TI  - A new method to determine carbon isotopic composition of dissolved inorganic
      carbon in seawater and pore waters by CO(2) -water equilibrium.
AB  - RATIONALE: Precise measurement of the carbon isotopic compositions of dissolved
      inorganic carbon (DIC) in water samples is very important for earth and
      environmental sciences, and the H(3) PO(4) acidification method has long been
      applied for this purpose. Due to the large variation in DIC concentration in
      various types of water samples, however, it is difficult to sample the optimized
      amount of water for high-precision mass spectrometry analysis and in many cases
      this has led to poor data quality. In addition, when the amount of water sample
      is very limited or when the water has a complicated composition such as seawater
      and saline marine pore waters, it is often difficult to obtain high-quality data
      using the conventional method. METHODS: Here we report a new method of obtaining
      CO(2) -water equilibrium for high-precision carbon isotope analysis of DIC in
      water samples. The instrument used was a Delta Plus XP stable isotope mass
      spectrometer coupled with an on-line a Gas Bench II sample preparation device. In
      general, 0.5 mL of water is sampled and equilibrated with CO(2) in headspace. The
      CO(2) is then transferred into the mass spectrometer and delta(13) C values are
      obtained. RESULTS: The delta(13) C values for four marine pore water samples
      determined by this new method are only slightly different (<0.150/00) from those
      determined using the conventional H(3) PO(4) method. The new method of obtaining
      CO(2) -water equilibrium also allows a constant amount of CO(2) for every sample
      to finally enter the mass spectrometer and hence better precision can be
      achieved. CONCLUSIONS: This new method is suitable for the measurement of both
      oxygen isotopic composition in water and carbon isotopic composition of DIC for
      seawater and pore water samples. Another benefit of this new method is that the
      water sample can be re-used for other further analyses and this is critical when
      the amount of sample is limited.

PMID- 22368061
TI  - Protein crystal content analysis by mass spectrometry and preliminary X-ray
      diffraction of a lectin from Canavalia grandiflora seeds with modulatory role in
      inflammation.
AB  - RATIONALE: Lectins are a family of proteins capable of deciphering the glycan
      code. Several authors have published works about crystallization and mass
      spectrometry analyses of ConA-like lectins. However, mass spectrometry has never
      been used to characterize lectin crystal content. In this study, Canavalia
      grandiflora lectin (ConGF), a ConA-like lectin, was crystallized, part of its
      primary structure sequenced and the pro-inflammatory activity evaluated. In
      addition, the crystal content was analyzed by mass spectrometry. METHODS: ConGF
      was crystallized in the presence of X-Man by hanging-drop vapor diffusion at 293
      K and the protein crystal content was analyzed by electrospray ionization in a
      SYNAPT HDMS mass spectrometer. Partial sequence was obtained by protein digestion
      with several proteolytic enzymes and the peptides sequenced by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). The pro-inflammatory
      potential of ConGF was also evaluated in the model of rat paw edema. RESULTS: The
      protein crystals consist of mature alpha chain and beta and gamma fragments
      measuring 25 612 +/- 2 Da, 12 962 +/- 2 Da and 12 667 +/- 2 Da, respectively. The
      crystal belongs to the orthorhombic space group I222 (unit cell parameters: a =
      67.70, b = 55.90, c = 107.46 A), assuming a monomer in the asymmetric unit. The
      solvent content was calculated as 43.50% and the protein content as 2.5 ug.
      Furthermore, a significant part of the primary structure (65.8%) was determined
      by mass spectrometry. CONCLUSIONS: As far as we know this is the first report of
      lectin crystal content characterized by mass spectrometry. Like other ConA-like
      lectins, GonGF induced paw edema however differing in potency and duration. The
      observed pro-inflammatory activity suggests that ConGF might be a useful tool in
      the study of inflammation processes and structure/function relationships.

PMID- 22368062
TI  - Improvement of estradiol esters monitoring in bovine hair by dansylation and
      liquid chromatography/tandem mass spectrometry analysis in multiple reaction
      monitoring and precursor ion scan modes.
AB  - RATIONALE: The control of forbidden anabolic practices in cattle in the European
      Union has become challenging since endogenous compounds such as estradiol
      derivatives can potentially be used as growth promoters. Due to the great
      difficulty in establishing a reference threshold value for endogenous steroids,
      the direct detection of steroid esters in hair is an efficient strategy for the
      detection of 'natural' steroid abuse in cattle. METHODS: The present study aimed
      to develop and validate according to the current European standards a specific
      liquid chromatography/tandem mass spectrometry (LC/MS/MS) analytical strategy to
      monitor estrogen esters in bovine hair. The analysis was performed by positive
      ion electrospray ionisation (ESI+) after dansylation. Two acquisition modes were
      then assessed: single reaction monitoring and precursor ion scanning. RESULTS:
      The results showed that the introduction of a dansylation step strongly improves
      the sensitivity of the detection of estradiol-17-esters by LC/(ESI+)-MS/MS. The
      CCalpha values are in the range 1-10 ng g(-1) after optimisation, except for
      estradiol decanoate for which the derivatisation is not efficient. In addition,
      this LC/MS/MS approach makes it possible to carry out a precursor ion scan to
      screen for the presence of these estradiol 17-esters in hair samples.
      CONCLUSIONS: Based on the specific product ions, i.e. m/z 255 in native
      conditions or m/z 171 after dansylation, this strategy has the advantage of
      detecting any (un)known estradiol ester and of giving access to the [M + H](+)
      ion of the suspected ester through only a single analysis.

PMID- 22368063
TI  - Study of fragmentation pathways of metastable negative ions in aliphatic
      dipeptides using the statistical theory.
AB  - RATIONALE: Dipeptide molecules are good model systems for investigation of
      resonant reactions of low-energy electrons with proteins. The present work is
      devoted to the study of the processes of formation and fragmentation of negative
      ions in aliphatic dipeptides glycyl-glycine and glycyl-alanine. The metastable
      decays of negative ions were detected in these objects, and have been
      investigated with the aim of clarification of the mechanisms of fragmentation.
      METHODS: The effective yield curves for negative ions as functions of electron
      energy were obtained using a magnetic sector mass spectrometer rebuilt for
      generation and detection of negative ions. For analysis of the observed
      metastable decays statistical and thermochemical approaches have been used.
      RESULTS: The ions structures, the enthalpies of formation of neutral and charged
      particles, and the rate constants of dissociative reactions have been found.
      CONCLUSIONS: Comparison of the experimental results with theoretical data leads
      to the conclusion that metastable ion decay proceeds with minimal structural
      changes avoiding complicated rearrangements and isomerization processes.

PMID- 22368064
TI  - Iberian ham typification by direct infusion electrospray and photospray
      ionization mass spectrometry fingerprinting.
AB  - RATIONALE: Iberian ham is a product of high commercial value whose quality mainly
      depends on breeding and feeding of pigs in an authorized way. Simple, fast,
      simple, reliable and high-throughput analytical methods are necessary to assure
      the quality of ham and for fraud prevention. Tandem mass spectrometry (MS/MS) is
      proposed as an advantageous alternative over other analytical techniques commonly
      used in this industry for product authentication. METHODS: The analytical
      approach is based on direct infusion electrospray mass spectrometry (ESI(+)-MS)
      of dichloromethane/methanol (60:40) extracts of ham intramuscular fat. Similarly,
      atmospheric pressure photoionization ionization mass spectrometry (APPI(+)-MS)
      was used with a flow injection analysis system for sample introduction with
      methanol/water (50%) as the mobile phase and toluene as the dopant. All
      experiments were performed on an API QSTAR(r) XL Hybrid system using both ESI and
      APPI sources. RESULTS: The ESI(+)-MS mass spectra present several clusters of
      peaks attributed to ammonium adducts [M + NH(4) (+) ] of lipid compounds (mono-,
      di- and triacylglycerols - MGs, DGs, TGs, and free fatty acids - FFAs), that can
      be identified by MS/MS spectra. On the other hand, the APPI(+)-MS spectra present
      [M + H(+) ] ions and reflect a higher fragmentation of the sample. Five different
      types of Iberian ham samples were successfully classified using partial least
      squares discriminant analysis (PLS-DA) of data from these samples. CONCLUSIONS:
      The application of direct infusion tandem mass spectrometry to
      dichloromethane/methanol extracts from intramuscular fat ham allows the simple,
      fast and reliable fingerprinting typification of different Iberian ham samples
      from pigs with different diets. With the proposed method, sample handling is
      minimal and chromatographic separation is not necessary, which represents an
      evident advantage over other analytical procedures usually used for this purpose.

PMID- 22368065
TI  - A reliable method by ultra-performance liquid chromatography coupled with tandem
      mass spectrometry to quantify and confirm simultaneously the presence of solvent
      metabolites in workers' urine.
AB  - Ultra-performance liquid chromatography coupled with tandem mass spectrometry was
      used for the biological monitoring of workers occupationally exposed to solvents.
      The method was developed using a triple quadrupole to investigate the relevant
      urinary metabolites of styrene, namely mandelic acid and phenylglyoxylic acid.
      The method provides quantitative and qualitative data to give additional
      assurance about the nature of the contaminant analyzed in workers' urine. A full
      scan and a product ion scan were acquired within the chromatographic peak
      acquired in MRM. For the two metabolites, the repeatability was 96%, the
      precision >=97%, and the accuracy >=93 +/- 3%. The quantitative performances were
      not influenced by the inclusion of simultaneous full scan acquisition as compared
      to a usual quantitative approach. Footprints of each substance of interest were
      obtained at each injection, and full scan data can be interrogated for the
      presence of interferences and other contaminants. The method developed has been
      submitted to random real samples from both non-occupationally and occupationally
      exposed workers. The urines of non-occupationally exposed workers were all free
      of mandelic acid, phenylglyoxylic acid and putative interferences showing the
      high selectivity of the method. However, the urines of occupationally exposed
      workers were robustly quantified. The levels of mandelic acid and phenylglyoxylic
      acid ranged between 0.2 and 9 mM, and the footprints of each metabolite and
      structural information were acquired in parallel with the quantitative results,
      thus providing unquestionable data about the nature of the contaminant and the
      levels reported. The combination of qualitative information acquired
      simultaneously with quantitative results provides the structural information
      needed in case of questions, without any harmful effect on the robustness and
      throughput of the quantitative analysis.

PMID- 22368066
TI  - Coupling solid-phase microextraction and laser desorption ionization for rapid
      identification of biological material.
AB  - RATIONALE: Solid phase microextraction (SPME) use small fibers directly plunged
      in the solution under investigation to quickly extract and quantify by different
      techniques the amount of selected dissolved compounds. METHODS: Biological
      materials, peptides or proteins are accurately identified by matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS). They are difficult to
      extract by SPME. This work looks for a chemical to be deposited onto fibers and
      able to act as a good SPME extractant as well as efficient matrix for MALDI
      detection. RESULTS: 3-Hydroxy-2-naphthoic acid (HNA) and 2-hydroxy-1-(2-hydroxy-4
      sulfo-1-naphthylazo)-3-naphthoic acid (HHSNNA) were compared to two classical
      matrices: alpha-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydrobenzoic acid
      (DHB). Bound to silica particles, DHB and HNA were found to be good MALDI
      matrices. Only the wide pore particles gave observable spectra. These particles
      were then attached in a thin layer onto wires to be used as fiber tips in SPME.
      Fibers loaded with peptides were introduced into the mass spectrometer to record
      fiber laser desorption ionization (FILDI) spectra. CONCLUSIONS: SPME-FILDI
      experiments could quickly identify peptides and proteins in solutions. More work
      is needed to find the best matrix and the way to fix it onto the fiber.

PMID- 22368067
TI  - Vacuum electrospray of volatile liquids assisted by infrared laser irradiation.
AB  - RATIONALE: Current large cluster sources such as C(60) or argon utilize gas-phase
      sources which are of low-brightness and cannot be focused efficiently to better
      than 1 micron diameter spot size. The development of a high-brightness large
      cluster ion source is of critical importance to achieve high resolution in
      secondary ion mass spectrometry (SIMS) imaging of organics. METHODS: We propose a
      new high-brightness large cluster ion source, and a technique for producing a
      stable electrospray of volatile liquids under vacuum. It is known that vacuum
      electrospray of volatile liquids such as water is extremely difficult because of
      freezing of the liquids introduced in vacuum by evaporative cooling. To avoid
      freezing, the tip of the electrospray emitter was irradiated by a continuous wave
      infrared laser. RESULTS: Without continuous laser irradiation the vacuum
      electrospray of a water/methanol solution was unstable with respect to the shapes
      of the Taylor cone and current, whereas continuous laser irradiation produced a
      stable electrospray of water. The typical modes of electrospray were clearly
      observed with an optical microscope even under vacuum conditions. A stable vacuum
      electrospray could be achieved by improving the vacuum pressure to suppress
      electric discharge and by using the laser to maintain the liquid state.
      CONCLUSIONS: This is the first description of the production of a stable vacuum
      electrospray of volatile liquids such as water. This vacuum electrospray
      technique can be expected to produce a novel high-brightness large cluster ion
      beam source.

PMID- 22368068
TI  - Chiral differentiation of amino acids by the kinetic method by Fourier transform
      ion cyclotron resonance mass spectrometry via a different dissociation pathway.

PMID- 22368069
TI  - Comment on "Tracing the sources of water using stable isotopes: first results
      along the Mangalore-Udupi region, south-west coast of India".

PMID- 22368071
TI  - Tungsten trioxide promoted selective conversion of cellulose into propylene
      glycol and ethylene glycol on a ruthenium catalyst.

PMID- 22368072
TI  - Characterization of cerium oxide nanoparticles-part 2: nonsize measurements.
AB  - Part 1 (see companion paper) of the present study discussed the application of a
      multimethod approach in characterizing the size of cerium oxide nanoparticles
      (NPs). However, other properties less routinely investigated, such as shape and
      morphology, structure, chemical composition, and surface properties, are likely
      to play an important role in determining the behavior, reactivity, and potential
      toxicity of these NPs. The present study describes the measurement of the
      aforementioned physicochemical properties of NPs (applied also to nanomaterials
      [NMs]) compared with micrometer particles (MPs). The authors use a wide range of
      techniques, including high resolution-transmission electron microscopy, scanning
      electron microscopy, atomic force microscopy, X-ray diffraction, X-ray energy
      dispersive spectroscopy, electron energy loss spectroscopy, X-ray photoelectron
      spectroscopy, and electrophoresis, and compare these techniques, their
      advantages, and their limitations, along with recommendations about how best to
      approach NM characterization, using an application to commercial cerium oxide NPs
      and MPs. Results show that both cerium oxide NPs and MPs are formed of single
      polyhedron or truncated polyhedron crystals. Cerium oxide NPs contain a mixture
      of Ce(3+) and Ce(4+) cations, whereas the MPs contain mainly Ce(4+) , which is
      potentially important in understanding the toxicity of cerium oxide NPs. The
      isoelectric point of cerium oxide NPs was approximately pH 8, which explains
      their propensity to aggregate in aqueous media (see companion paper).

PMID- 22368073
TI  - Inactivation of a low temperature-induced RNA helicase in Synechocystis sp. PCC
      6803: physiological and morphological consequences.
AB  - Inactivation of the DEAD box RNA helicase, crhR, has dramatic effects on the
      physiology and morphology of the photosynthetic cyanobacterium, Synechocystis sp.
      PCC 6803. These effects are observed at both normal growth temperature (30
      degrees C) and under cold stress (20 degrees C), indicating that CrhR performs
      crucial function(s) at all temperatures. A major physiological effect is the
      rapid cessation of photosynthesis upon temperature downshift from 30 to 20
      degrees C. This defect does not originate from an inability to transport or
      accumulate inorganic carbon or a deficiency in photosynthetic capacity as the
      mutant has sufficient electron transport and enzymatic capacity to sustain
      photosynthesis at 30 degrees C and inorganic carbon (Ci) accumulation at 20
      degrees C. Oxygen consumption in the presence of methyl viologen indicated that
      while electron transport capacity is sufficient to accumulate Ci, the mutant does
      not possess sufficient activity to sustain carbon fixation at maximal rates.
      These defects are correlated with severely impaired cell growth and decreased
      viability, cell size and DNA content at low temperature. The DeltacrhR mutant
      also progressively accumulates structural abnormalities at low temperature that
      cannot be attributed solely to reactive oxygen species (ROS)-induced
      photooxidative damage, suggesting that they are manifestations of pre-existing
      defects that are amplified over time. The data indicate that the observed
      physiological and morphological effects are intimately related to crhR mutation,
      implying that the lack of CrhR RNA unwinding/annealing activity results in the
      inability to execute one or more vital steps in photosynthesis that are required
      at all temperatures but are crucial at low temperature.

PMID- 22368074
TI  - Genome-wide identification, functional analysis and expression profiling of the
      Aux/IAA gene family in tomato.
AB  - Auxin is a central hormone that exerts pleiotropic effects on plant growth
      including the development of roots, shoots, flowers and fruit. The perception and
      signaling of the plant hormone auxin rely on the cooperative action of several
      components, among which auxin/indole-3-acetic acid (Aux/IAA) proteins play a
      pivotal role. In this study, we identified and comprehensively analyzed the
      entire Aux/IAA gene family in tomato (Solanum lycopersicum), a reference species
      for Solanaceae plants, and the model plant for fleshy fruit development.
      Functional characterization using a dedicated single cell system revealed that
      tomato Aux/IAA proteins function as active repressors of auxin-dependent gene
      transcription, with, however, different Aux/IAA members displaying varying levels
      of repression. Phylogenetic analysis indicated that the Aux/IAA gene family is
      slightly contracted in tomato compared with Arabidopsis, with a lower
      representation of non-canonical proteins. Sl-IAA genes display distinctive
      expression pattern in different tomato organs and tissues, and some of them
      display differential responses to auxin and ethylene, suggesting that Aux/IAAs
      may play a role in linking both hormone signaling pathways. The data presented
      here shed more light on Sl-IAA genes and provides new leads towards the
      elucidation of their function during plant development and in mediating hormone
      cross-talk.

PMID- 22368075
TI  - On the choice of health inequality measure for the longitudinal analysis of
      income-related health inequalities.
AB  - Changes in rank-dependent income-related health inequality measures over time may
      usefully be decomposed into contributions due to changes in health outcomes and
      changes in individuals' positions in the income distribution. This paper
      establishes the normative implications of this type of decomposition by embedding
      it within a broader analysis of changes in the 'health achievement' index. We
      further show that the choice of health inequality measure implies a particular
      vertical equity judgement, which may be expressed on a common scale in terms of
      the concentration index of health changes that would be inequality preserving. We
      illustrate the empirical implications of this choice by reporting results from a
      longitudinal analysis of changes in income-related health inequality in Great
      Britain using the concentration, the Erreygers and Wagstaff indices of health
      attainments and the concentration index of health shortfalls. .

PMID- 22368076
TI  - Evaluation of the quality of postharvest rapeseed by means of an electronic nose.
AB  - BACKGROUND: Rapeseed is a valuable source of edible oil. The presence of even a
      small amount of mouldy or burnt rapeseed in a particular production batch
      deteriorates the quality of the edible oil obtained from it. Since the
      traditional method of using a panel of experts is time-consuming, there is a need
      for fast and easy methods for rapeseed quality evaluation by intelligent devices
      to replace human labour. RESULTS: For rapeseed quality evaluation, an electronic
      nose equipped with an array of eight quartz microbalance sensors and four metal
      oxide semiconductor sensors was used. Signals generated by the sensors were
      analysed by principal component analysis and discriminant function analysis.
      Identification of samples that contained small proportions of mouldy or burnt
      rapeseed was possible despite the differences between the particular varieties
      studied. CONCLUSION: Electronic nose technology has shown the possibility of
      detecting samples of faulty rapeseed at very low contamination levels and
      distinguishing them with high probability from sound rapeseed.

PMID- 22368077
TI  - Double-lumen tube placement with the patient in the supine position without a
      headrest minimizes displacement during lateral positioning.
AB  - PURPOSE: The correct position of double-lumen tubes (DLTs) is customarily
      confirmed after tracheal intubation by bronchoscopy with the patient supine on a
      headrest. However, displacement of DLTs usually occurs during lateral positioning
      because of neck extension. This study was undertaken to determine whether
      displacement of DLTs could be minimized during lateral positioning if DLTs were
      positioned without a headrest. METHODS: One hundred patients scheduled for
      thoracic surgery were randomized into two groups (n = 50 each). After tracheal
      intubation using a headrest, adjustment of DLT position was performed according
      to group assignment, i.e., either with the headrest in place or without the
      headrest. Using a bronchoscope, distances from the tracheal opening to the main
      carina and from the bronchial opening to the left bronchial carina were measured
      in both the supine and lateral positions. RESULTS: Displacement of DLTs [mean
      (standard deviation)] during lateral positioning was greater in the headrest
      group than in the no-headrest group [12.3 (6.5) mm vs 6.8 (5.5) mm, respectively,
      in the trachea; 11.6 (6.7) mm vs 6.0 (4.6) mm, respectively, in the bronchus; P <
      0.001]. The incidence of significant displacement, defined as > 10 mm from
      initial correct position, was greater in the headrest group than in the no
      headrest group (64% vs 28%, respectively, in the trachea; 58% vs 20%,
      respectively, in the bronchus; P < 0.001). CONCLUSION: Displacement of DLTs
      during lateral positioning appears to be caused primarily by extension of the
      neck. Correct adjustment of DLT position without a headrest in the supine
      position is an easy and effective method to minimize DLT displacement during
      lateral positioning.

PMID- 22368078
TI  - A trigonometric method to confirm needle tip position during out-of-plane
      ultrasound-guided regional blockade.

PMID- 22368079
TI  - Unique effects of apathy and depression signs on cognition and function in
      amnestic mild cognitive impairment.
AB  - OBJECTIVE: Apathy and depression are the most common neuropsychiatric features in
      mild cognitive impairment (MCI). These syndromes have been linked to cognitive
      and functional decline. This study aimed to examine their unique relationships
      with specific cognitive abilities and daily functioning among MCI patients with
      memory impairment (amnestic MCI). METHODS: Data from 90 individuals referred for
      outpatient clinical neuropsychological evaluation and subsequently characterized
      as having amnestic MCI were obtained from a memory disorders center. MCI was
      defined using current NIA-Alzheimer's Association criteria. Variables included
      caregiver-reported apathy (Frontal Systems Behavior Scale) and depression (Memory
      and Behavioral Problems Checklist), scores on neuropsychological measures, and
      the Lawton-Brody Instrumental Activities of Daily Living Scale. Data were
      analyzed with multiple regressions controlling for age and education. RESULTS:
      Depression was independently associated with composite scores of executive
      functioning. Neither apathy nor depression was associated with composite scores
      of attention, memory, or language. With regard to individual measures of
      executive functioning, depression was independently associated with poorer set
      shifting (i.e., Trails B). Apathy was independently associated with poorer letter
      fluency (i.e., FAS). Apathy, but not depression, was associated with greater
      functional impairment. CONCLUSIONS: Apathy and depression are associated with
      different aspects of executive functioning in amnestic MCI, which may reflect
      differing patterns of frontal lobe pathology. Apathy exerts a greater impact on
      daily functioning than depression and may therefore increase reliance on
      caregivers. Results support the separability of apathy and depression in amnestic
      MCI. Clinicians should differentiate these neuropsychiatric states during
      assessment and treatment.

PMID- 22368080
TI  - The synchronization within and interaction between the default and dorsal
      attention networks in early infancy.
AB  - An anticorrelated interaction between the dorsal attention and the default-mode
      networks has been observed, although how these 2 networks establish such
      relationship remains elusive. Behavioral studies have reported the emergence of
      attention and default network-related functions and a preliminary competing
      relationship between them at early infancy. This study attempted to test the
      hypothesis--resting-state functional magnetic resonance imaging will demonstrate
      not only improved network synchronization of the dorsal attention and the default
      networks, respectively, during the first 2 years of life but also an
      anticorrelated network interaction pattern between the 2 networks at 1 year which
      will be further enhanced at 2 years old. Our results demonstrate that both
      networks start from an isolated region in neonates but evolve to highly
      synchronized networks at 1 year old. Paralleling the individual network
      maturation process, the anticorrelated behaviors are absent at birth but become
      apparent at 1 year and are further enhanced during the second year of life. Our
      studies elucidate not only the individual maturation process of the dorsal
      attention and default networks but also offer evidence that the maturation of the
      individual networks may be needed prior exhibiting the adult-like interaction
      patterns between the 2 networks.

PMID- 22368081
TI  - A gene-brain-cognition pathway: prefrontal activity mediates the effect of COMT
      on cognitive control and IQ.
AB  - A core thesis of cognitive neurogenetic research is that genetic effects on
      cognitive ability are mediated by specific neural functions, however,
      demonstrating neural mediation has proved elusive. Pairwise relationships between
      genetic variation and brain function have yielded heterogeneous findings to date.
      This heterogeneity indicates that a multiple mediator modeling approach may be
      useful to account for complex relationships involving function at multiple brain
      regions. This is relevant not only for characterizing healthy cognition but for
      modeling the complex neural pathways by which disease-related genetic effects are
      transmitted to disordered cognitive phenotypes in psychiatric illness. Here, in
      160 genotyped functional magnetic resonance imaging participants, we used a
      multiple mediator model to test a gene-brain-cognition pathway by which activity
      in 4 prefrontal brain regions mediates the effects of catechol-O
      methyltransferase (COMT) gene on cognitive control and IQ. Results provide
      evidence for gene-brain-cognition mediation and help delineate a pathway by which
      gene expression contributes to intelligence.

PMID- 22368082
TI  - Integration of opposing semaphorin guidance cues in cortical axons.
AB  - Previous work demonstrated that members of the semaphorin family, Sema3A and
      Sema3C, act as repulsive and attractive guidance signals, respectively, for
      cortical axons. During the development of corticofugal projections, these
      semaphorins are expressed in adjacent cortical zones, but there is a considerable
      overlap between Sema3A and Sema3C expression in the subventricular zone. We used
      different in vitro assays to examine the response of cortical axons exposed to
      defined mixtures of these opposing guidance cues. Results showed that even at
      very low concentrations, Sema3A overrides the effects of Sema3C. Moreover,
      experiments with function-blocking antibodies directed against neuropilin
      provided insights into how cortical axons integrate disparate guidance signals at
      the receptor level. These in vitro data suggest that the pathway of corticofugal
      axons is defined by an attractive cue in the intermediate zone, where Sema3C is
      expressed alone. To directly test this hypothesis in vivo, we performed axon
      tracing experiments in Sema3C-deficient mice. Compared with wild-type animals,
      corticofugal axons take a more superficial route in Sema3C(-/-) mice, and the
      corticofugal pathway is more compacted. This phenotype is expected when an
      attractive cue for cortical axons, Sema3C, is eliminated and a repulsive cue,
      Sema3A, becomes predominant.

PMID- 22368083
TI  - Synaptic and extrasynaptic origin of the excitation/inhibition imbalance in the
      hippocampus of synapsin I/II/III knockout mice.
AB  - Synapsins (Syn I, Syn II, and Syn III) are a family of synaptic vesicle
      phosphoproteins regulating synaptic transmission and plasticity. SYN1/2 genes
      have been identified as major epilepsy susceptibility genes in humans and
      synapsin I/II/III triple knockout (TKO) mice are epileptic. However, excitatory
      and inhibitory synaptic transmission and short-term plasticity have never been
      analyzed in intact neuronal circuits of TKO mice. To clarify the generation and
      expression of the epileptic phenotype, we performed patch-clamp recordings in the
      CA1 region of acute hippocampal slices from 1-month-old presymptomatic and 6
      month-old epileptic TKO mice and age-matched controls. We found a strong
      imbalance between basal glutamatergic and gamma-aminobutyric acid (GABA)ergic
      transmission with increased evoked excitatory postsynaptic current and impaired
      evoked inhibitory postsynaptic current amplitude. This imbalance was accompanied
      by a parallel derangement of short-term plasticity paradigms, with enhanced
      facilitation of glutamatergic transmission in the presymptomatic phase and milder
      depression of inhibitory synapses in the symptomatic phase. Interestingly, a
      lower tonic GABA(A) current due to the impaired GABA release is responsible for
      the more depolarized resting potential found in TKO CA1 neurons, which makes them
      more susceptible to fire. All these changes preceded the appearance of epilepsy,
      indicating that the distinct changes in excitatory and inhibitory transmission
      due to the absence of Syns initiate the epileptogenic process.

PMID- 22368084
TI  - Borders and comparative cytoarchitecture of the perirhinal and postrhinal
      cortices in an F1 hybrid mouse.
AB  - We examined the cytoarchitectonic and chemoarchitectonic organization of the
      cortical regions associated with the posterior rhinal fissure in the mouse brain,
      within the framework of what is known about these regions in the rat. Primary
      observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1
      hybrid was chosen because of the many advantages afforded in the study of the
      molecular and cellular bases of learning and memory. Comparisons with the parent
      strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was
      processed for visualization of Nissl material, myelin, acetyl cholinesterase,
      parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm's
      method was particularly useful in the assignment of borders and in the
      comparative analyses because the patterns of staining were similar across species
      and strains. As in the rat, the areas examined were parcellated into 2 regions,
      the perirhinal and the postrhinal cortices. The perirhinal cortex was divided
      into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd)
      and ventral (PORv) subregions. In addition to identifying the borders of the
      perirhinal cortex, we were able to identify a region in the mouse brain that
      shares signature features with the rat postrhinal cortex.

PMID- 22368085
TI  - Spatial and temporal variations of cortical growth during gyrogenesis in the
      developing ferret brain.
AB  - Spatial and temporal variations in cortical growth were studied in the neonatal
      ferret to illuminate the mechanisms of folding of the cerebral cortex. Cortical
      surface representations were created from magnetic resonance images acquired
      between postnatal day 4 and 35. Global measures of shape (e.g., surface area,
      normalized curvature, and sulcal depth) were calculated. In 2 ferrets, relative
      cortical growth was calculated between surfaces created from in vivo images
      acquired at P14, P21, and P28. The isocortical surface area transitions from a
      slower (12.7 mm(2)/day per hemisphere) to a higher rate of growth (36.7 mm(2)/day
      per hemisphere) approximately 13 days after birth, which coincides with the time
      of transition from neuronal proliferation to cellular morphological
      differentiation. Relative cortical growth increases as a function of relative
      geodesic distance from the origin of the transverse neurogenetic gradient and is
      related to the change in fractional diffusion anisotropy over the same time
      period. The methods presented here can be applied to study cortical growth during
      development in other animal models or human infants. Our results provide a
      quantitative spatial and temporal description of folding in cerebral cortex of
      the developing ferret brain, which will be important to understand the underlying
      mechanisms that drive folding.

PMID- 22368086
TI  - Cerebral correlates of salient prediction error for different rewards and
      punishments.
AB  - Learning to predict rewarding and aversive outcomes is based on the comparison
      between predicted and actual outcomes (prediction error: PE). Recent
      electrophysiological studies reported that during a Pavlovian procedure some
      dopamine neurons code a classical PE signal while a larger population of
      dopaminergic neurons reflect a "salient" prediction error (SPE) signal, being
      excited both by unpredictable aversive events and by rewards. Yet, it is still
      unclear whether specific human brain structures receiving afferents from
      dopaminergic neurons code a SPE and whether this signal depends upon reinforcer
      type. Here, we used a model-based functional magnetic resonance imaging approach
      implementing a reinforcement learning model to compute the PE while subjects
      underwent a Pavlovian conditioning procedure with 2 types of rewards (pleasant
      juice and monetary gain) and 2 types of punishments (aversive juice and aversive
      picture). The results revealed that activity of a brain network composed of the
      striatum, anterior insula, and anterior cingulate cortex covaried with a SPE for
      appetitive and aversive juice. Moreover, amygdala activity correlated with a SPE
      for these 2 reinforcers and for aversive pictures. These results provide insights
      into the neurobiological mechanisms underlying the ability to learn stimuli
      rewards and stimuli-punishments contingencies, by demonstrating that the network
      reflecting the SPE depends upon reinforcement's type.

PMID- 22368088
TI  - Reappraising the ultimatum: an fMRI study of emotion regulation and decision
      making.
AB  - Emotion regulation strategies provide a means by which to modulate our social
      behavior. In this study, we investigated the effect of using reappraisal to both
      up- and downregulate social decision making. After being instructed on how to use
      reappraisal, participants played the Ultimatum Game while undergoing functional
      magnetic resonance imaging and applied the strategies of upregulation
      (reappraising the proposer's intentions as more negative), down-regulation
      (reappraising the proposer's intentions as less negative), as well as a baseline
      "look" condition. As hypothesized, when reappraising, decision acceptance rates
      were altered, with a greater number of unfair offers accepted while down
      regulating and a greater number of unfair offers rejected while upregulating,
      both relative to the baseline condition. At the neural level, during reappraisal,
      significant activations were observed in the inferior and middle frontal gyrus
      (MFG), in addition to the medial prefrontal cortex and cingulate gyrus for unfair
      offers only. Regulated decisions involved left inferior frontal gyrus for
      upregulation and MFG for down-regulation strategies, respectively. Importantly,
      the effects of emotion modulation were evident in posterior insula, with less
      activation for down-regulation and more activation for upregulation in these
      areas. Notably, we show for the first time that top-down strategies such as
      reappraisal strongly affect our socioeconomic decisions.

PMID- 22368087
TI  - Asymmetries of the parietal operculum in chimpanzees (Pan troglodytes) in
      relation to handedness for tool use.
AB  - A left larger than right planum temporale (PT) is a neuroanatomical asymmetry
      common to both humans and chimpanzees. A similar asymmetry was observed in the
      human parietal operculum (PO), and the convergence of PT and PO asymmetries is
      strongly associated with right-handedness. Here, we assessed whether this
      combination also exists in common chimpanzees. Magnetic resonance scans were
      obtained in 83 captive subjects. PT was quantified following procedures
      previously employed and PO was defined as the maximal linear distance between the
      end point of the sylvian fissure and the central sulcus. Handedness was assessed
      using 2 tasks that were designed to simulate termite fishing of wild chimpanzees
      and to elicit bimanual coordination without tool use. Chimpanzees showed
      population-level leftward asymmetries for both PT and PO. As in humans, these
      leftward asymmetries were not correlated. Handedness for tool use but not for
      nontool use motor actions mediated the expression of asymmetries in PT and PO,
      with right-handed apes showing more pronounced leftward asymmetries. Consistent
      PT and PO asymmetry combinations were observed in chimpanzees. The proportions of
      individuals showing these combinations were comparable in humans and chimpanzees;
      however, interaction between handedness and patterns of combined PO and PT
      asymmetries differed between the 2 species.

PMID- 22368093
TI  - A protein biosensor that relies on bending of single DNA molecules.
AB  - A "bendy" protein sensor: A DNA-based sensor that uses folded DNA (through DNA
      kinks) and protein-induced bending to detect DNA-binding proteins is presented.
      Single-molecule sensing of a transcriptional activator (catabolite activator
      protein, CAP, which bends its DNA site by 80 degrees ) is demonstrated in
      solution and on surfaces, both in buffers and in cell lysates. The method should
      allow detection of a wide range of DNA-bending proteins.

PMID- 22368089
TI  - The development and activity-dependent expression of aggrecan in the cat visual
      cortex.
AB  - The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate
      proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus
      (dLGN). During development, aggrecan expression increases in the dLGN with a time
      course that matches the decline in plasticity. Moreover, examination of tissue
      from selectively visually deprived cats shows that expression is activity
      dependent, suggesting a role for aggrecan in the termination of the sensitive
      period. Here, we demonstrate for the first time that the onset of aggrecan
      expression in area 17 also correlates with the decline in experience-dependent
      plasticity in visual cortex and that this expression is experience dependent.
      Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan
      positive neurons in the extragranular layers, but not in layer IV. This effect
      was reversible as dark-reared animals that were subsequently exposed to light
      showed normal numbers of Cat-301-positive cells. The reduction in aggrecan
      following certain early deprivation regimens is the first biochemical correlate
      of the functional changes to the gamma-aminobutyric acidergic system that have
      been reported following early deprivation in cats.

PMID- 22368092
TI  - A novel method for simultaneous 3D B(1)  and T(1)  mapping: the method of slopes
      (MoS).
AB  - A novel three-dimensional simultaneous B(1) and T(1) mapping method is
      introduced: the method of slopes (MoS). The linearity of the spoiled gradient
      recalled echo (SPGR) signal vs flip angle relation is exploited: B(1) mapping is
      achieved by a two-point extrapolation to signal null with a correction scheme
      while T(1) mapping uses the slopes of the SPGR signal vs flip angle curves near
      the origin and near the signal null. This new method improves upon the existing
      variable flip angle (VFA) T(1)-mapping method in that (i) consistency between
      B(1) and T(1) maps is ensured (ii) the sampling scheme is T(1)-independent (iii)
      the noise bias and singularity, associated with using a linear form for the SPGR
      signal equation, is eliminated by using the full equation. The method is shown to
      yield accurate and robust results via simulations. Initial estimates of B(1) and
      T(1) values are obtained from three data points via simple computations and
      straight line approximations. Initial estimates of B(1) values, for a range of
      values, are shown to be accurate due to the proposed B(1) correction scheme. The
      accuracy and robustness of T(1) values is achieved via a non-linear fitting
      algorithm which includes a fourth data point sampled at high SNR. The MoS was
      validated by comparing resulting B(1) and T(1) maps with those obtained using
      other standard methods. Finally, the ability to obtain brain B(1) and T(1) maps
      using the MoS was demonstrated by in vivo experiments. The MoS is expected to
      perform well on other motion-free anatomical regions as well.

PMID- 22368094
TI  - In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: safety and
      feasibility.
AB  - (31)P MR spectroscopic imaging of the human prostate provides information about
      phosphorylated metabolites that could be used for prostate cancer
      characterization. The sensitivity of a magnetic field strength of 7 T might
      enable 3D (31)P MR spectroscopic imaging with relevant spatial resolution in a
      clinically acceptable measurement time. To this end, a (31)P endorectal coil was
      developed and combined with an eight-channel (1)H body-array coil to relate
      metabolic information to anatomical location. An extensive safety validation was
      performed to evaluate the specific absorption rate, the radiofrequency field
      distribution, and the temperature distribution of both coils. This validation
      consisted of detailed Finite Integration Technique simulations, confirmed by MR
      thermometry and B 1+ measurements in a phantom and in vivo temperature
      measurements. The safety studies demonstrated that the presence of the (31)P
      endorectal coil had no influence on the specific absorption rate levels and
      temperature distribution of the external eight-channel (1)H array coil. To stay
      within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time
      averaged input power of 33 W for the (1)H array coil was allowed. For
      transmitting with the (31)P endorectal coil, our safety limit of less than 1
      degrees C temperature increase in vivo during a 15-min MR spectroscopic imaging
      experiment was reached at a time-averaged input power of 1.9 W. With this power
      setting, a second in vivo measurement was performed on a healthy volunteer. Using
      adiabatic excitation, 3D (31)P MR spectroscopic imaging produced spectra from the
      entire prostate in 18 min with a spatial resolution of 4 cm(3). The spectral
      resolution enabled the separate detection of phosphocholine, phosphoethanolamine,
      inorganic phosphate, and other metabolites that could play an important role in
      the characterization of prostate cancer.

PMID- 22368095
TI  - Practice analysis of nutrition support professionals: evidence-based
      multidisciplinary nutrition support certification examination.
AB  - BACKGROUND: The National Board of Nutrition Support Certification (NBNSC) is an
      independent credentialing board responsible for administering the
      multidisciplinary certification examination in nutrition support. For an exam to
      be legally and practically defensible, it must represent practice. Validation is
      by practice audit, the highest level of supporting evidence. OBJECTIVES: To
      define the role of the nutrition support professional (NSP) and the current
      elements (knowledge and functions) required for competent NSP practice. METHODS:
      A survey instrument was constructed using a content validation strategy to
      establish the link between job tasks and the content of the examination. Internet
      based surveys were made available to 5100 NSPs. NSP duties performed and
      knowledge required for patient safety and welfare were analyzed for the group as
      a whole and for each profession separately. RESULTS: A total of 765 surveys were
      completed (return rate of 15%). The results of the practice audit demonstrate a
      common core of practice across the nutrition support disciplines as well as a
      universal core of elements believed to be important for competent nutrition
      support practice. CONCLUSION: The results of this survey continue to support a
      common core of practice across nutrition support disciplines as well as a common
      core of elements believed to be important for competent nutrition support
      practice. Accordingly, the NBNSC will continue to offer one examination to all
      disciplines both nationally and internationally and confer the Certified
      Nutrition Support Clinician (CNSC) credential to all individuals who successfully
      pass this validated examination.

PMID- 22368096
TI  - Percutaneous gastrostomy tube placement using a balloon catheter in patients with
      head and neck cancer.
AB  - BACKGROUND: Patients with head and neck cancer frequently require gastrostomy
      feeding. The aim of this study was to evaluate the safety and feasibility of
      percutaneous radiologic gastrostomy with push-type gastrostomy tubes using a
      rupture-free balloon (RFB) catheter under computed tomography (CT) and
      fluoroscopic guidance in patients with head and neck cancer with swallowing
      disturbance or trismus. METHODS: Percutaneous CT and fluoroscopic gastrostomy
      placement of push-type gastrostomy tubes using a RFB catheter was performed in
      consecutive patients with head and neck cancer between April 2007 and July 2010.
      The technical success, procedure duration, and major or minor complications were
      evaluated. RESULTS: Twenty-one patients (14 men, 7 women; age range, 55-78 years;
      mean age, 69.3 years) underwent gastrostomy tube placement. The tumor location
      was the pharynx (n = 8), oral cavity (n = 7), and gingiva (n = 6). Gastrostomy
      was performed in 15 patients during treatment and 6 patients after treatment.
      Percutaneous radiologic gastrostomy was technically successful in all patients.
      The median procedure time was 35 +/- 19 (interquartile range) minutes (range, 25
      75). The average follow-up time interval was 221 days (range, 10-920 days). No
      major complications related to the procedure were encountered. No tubes failed
      because of blockage, and neither tube dislodgement nor intraperitoneal leakage
      occurred during the follow-up periods. CONCLUSION: Percutaneous CT and
      fluoroscopic-guided gastrostomy with push-type tubes using a RFB catheter is a
      relatively safe and effective means of gastric feeding, with high success and low
      complication rates in patients with head and neck cancer in whom endoscopy was
      not feasible.

PMID- 22368098
TI  - [Acute oral hemorrhage after radiotherapy of an oropharyngeal carcinoma].

PMID- 22368099
TI  - [The different hearing loss--easily curable!].

PMID- 22368100
TI  - [From the expert's office: is the use of hearing aids in noise areas allowed? New
      developments in the hearing aid sector!].

PMID- 22368101
TI  - [Head impulse test and vibratory test in the diagnosis of vertigo].
AB  - One of the most important questions within the field of vertigo-diagnosis is the
      proof or the exclusion of a vestibular impairment, the spectrum of appropriate
      diagnostic tools has been expanded by the head impulse test and the vibratory
      test in the last years. The head impulse test is a method to examine the
      functionality of single semicircular canals. As clinical "bedside test" it is an
      already established part of the diagnostic procedures, as an apparative method
      with registration and quantitative analysis, however, it is available for general
      in-office use only recently. The vibratory test is a method for provoking non
      spontaneous nystagmus. As a basis of a sophisticated vestibular diagnosis the
      test is less suitable, however, it is an absolutely valuable method to detect
      peripheral or central vestibular imbalances. In this regard the vibratory test is
      superior to other methods as for example the head shaking test. In the following
      article an overview concerning the physiological, methodical, and clinical
      aspects of the head impulse test and the vibratory test will be given.

PMID- 22368102
TI  - [Not Available].

PMID- 22368104
TI  - Characterisation of antioxidant compounds in sweet bell pepper (Capsicum annuum
      L.) under organic and conventional growing systems.
AB  - BACKGROUND: Sweet red bell pepper is one of the best sources of ascorbic acid and
      carotenoids as well as phenolic compounds important in the human diet. There have
      been some studies showing a higher level of bioactive compounds in organic bell
      pepper fruits compared with conventional fruits, but not all studies have been
      consistent in this respect. The levels of carotenoids and phenolics are very
      variable and may be affected by ripeness, genotype and cultivation. RESULTS: The
      results obtained in this study showed that an organic growing system affected the
      level of bioactive compounds (carotenoids and polyphenols) in sweet bell pepper
      fruits cultivated in Poland. Organic bell pepper fruits contained significantly
      more dry matter, vitamin C, total carotenoids, beta-carotene, alpha-carotene, cis
      beta-carotene, total phenolic acids (as well as individual gallic and chlorogenic
      acids) and flavonoids (quercetin D-glucoside, quercetin and kaempferol) compared
      with conventional fruits. The bell pepper variety also affected the level of
      antioxidant compounds in fruits. CONCLUSION: Organic growing increased the level
      of antioxidant compounds such as carotenoids, phenolic compounds and vitamin C in
      sweet bell pepper. The second significant factor affecting the antioxidant
      compound content of sweet bell pepper was variety. It would be necessary to
      continue this study as a long-term experiment in order to eliminate the influence
      of seasonality.

PMID- 22368105
TI  - The wide variation of definitions of genetic testing in international
      recommendations, guidelines and reports.
AB  - In spite of being very commonly used, the term genetic testing is debatable and
      used with several meanings. The diversity of existing definitions is confusing
      for scientists, clinicians and other professionals, health authorities,
      legislators and regulating agencies and the civil society in general,
      particularly when genetic testing is the object of guidelines or legal documents.
      This work compares definitions of genetic testing found in recommendations,
      guidelines and reports from international institutions, policy makers and
      professional organizations, but also in documents from other stakeholders in the
      field, as the pharmaceutical industry, insurers, ethics bodies, patient
      organizations or human-rights associations. A systematic review of these
      documents confirmed the extreme variability existing in the concepts and the
      ambiguous or equivocal use of the term. Some definitions (narrower) focus on
      methodologies or the material analysed, while others (broader) are information-
      or context-based. Its scope may range from being synonymous of just DNA analysis,
      to any test that yields genetic data. Genetic testing and genetic information,
      which may be derived from a range of medical exams or even family history, are
      often used interchangeably. Genetic testing and genetic screening are sometimes
      confused. Human molecular genetics (a discipline) is not always distinguished
      from molecular biology (a tool). Professional background, geographical context
      and purpose of the organizations may influence scope and usage. A common
      consensus definition does not exist. Nevertheless, a clear set of precise
      definitions may help creating a common language among geneticists and other
      health professionals. Moreover, a clear context-dependent, operative definition
      should always be given.

PMID- 22368106
TI  - Reoperation for bleeding in cardiac surgery.
AB  - At Odense University Hospital (OUH), 5-9% of all unselected cardiac surgical
      patients undergo reoperation due to excessive bleeding. The reoperated patients
      have an approximately three times greater mortality than non-reoperated. To
      reduce the rate of reoperations and mortality due to postoperative bleeding, we
      aim to identify risk factors that predict reoperation. A total of 1452
      consecutive patients undergoing cardiac surgery using extracorporeal circulation
      (ECC) between November 2005 and December 2008 at OUH were analysed. Statistical
      tests were used to identify risk factors for reoperation. We performed a case
      note review on propensity-matched patients to assess the outcome of reoperation
      for bleeding regarding morbidity and mortality. In total, 101 patients (7.0%)
      underwent surgical re-exploration due to excessive postoperative bleeding.
      Significant risk factors for reoperation for bleeding after cardiac surgery was
      low ejection fraction, high EuroSCORE, procedures other than isolated CABG,
      elongated time on ECC, low body mass index, diabetes mellitus and preoperatively
      elevated s-creatinine. Reoperated patients significantly had a greater increase
      in postoperative s-creatinine and higher mortality. Surviving reoperated patients
      significantly had a lower EuroSCORE and a shorter time on ECC compared with non
      survivors. The average time to re-exploration was 155 min longer for non
      survivors when compared with survivors.

PMID- 22368107
TI  - Successful use of a military haemostatic agent in patients undergoing
      extracorporeal circulatory assistance and delayed sternal closure.
AB  - We report the successful control of bleeding in two patients who underwent post
      cardiotomy extracorporeal circulatory support (ECMO) and then developed life
      threatening bleeding due to severe coagulopathy. After the failure of
      conventional techniques, bleeding control was achieved using Celox Gauze
      (MedTrade Products Ltd, Cheshire, UK) packed on the sternal edges and pericardial
      cavity.

PMID- 22368108
TI  - Should oesophagectomy be performed with cervical or intrathoracic anastomosis?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was: In [patients undergoing oesophagectomy for oesophageal
      cancer] is a [cervical anastomosis or intrathoracic anastomosis] superior in
      terms of [post-operative outcomes]. In total, 47 papers were found suitable using
      the reported search, and nine of these represented the best evidence to answer
      the clinical question. The authors, date, journal, study type, population, main
      outcome measures and results are tabulated. We conclude that there is no
      convincing evidence that cervical anastomosis is superior to intrathoracic
      anastomosis with respect to post-operative outcomes. Only one prospective study
      showed significantly increased risk of anastomotic leak with cervical
      anastomosis, but this study was significantly limited due to patient selection
      and variations in surgical approach and technique. Cervical anastomosis was also
      shown to increase pharyngeal reflux on pH monitoring compared with intrathoracic
      anastomosis, but this did not influence symptoms or development of subsequent
      anastomotic complications. One randomized study showed intrathoracic anastomosis
      significantly increased risk of respiratory complications, but in this study
      patient treatment was variable and study design was limited. Intrathoracic
      anastomosis was also shown to correlate with anastomotic stricture formation and
      this was attributed to increased anastomotic stapling in this patient group
      compared with cervical anastomosis. Post-operative pain as measured by grouped
      symptom scales significantly increased with intrathoracic anastomosis compared
      with cervical anastomosis. This did not correlate with development of other
      cardiorespiratory complications and the difference between the two groups
      resolved within 24 months. Overall, there is currently insufficient evidence to
      show a significant difference between cervical and intrathoracic anastomosis with
      respect to post-operative complications and hospital mortality. The wide variety
      in methodology and outcomes reinforce the need for further randomized trials to
      more accurately establish significant differences in outcomes.

PMID- 22368109
TI  - Midterm follow-up dynamic echocardiography evaluation after aortic valve repair
      for aortic valve insufficiency.
AB  - We prospectively evaluated 46 patients who underwent aortic valve repair (AVR)
      for AV regurgitation. Rest/stress echocardiography follow-up was performed.
      Follow-up duration was 30.7 months, age 56 +/- 14 years, ejection fraction% 57.5
      +/- 10.5%. Preoperative bicuspid AV was present in 14 (30.4%), leaflets
      calcifications in 8 (17.4%), thickening in 17 (37.0%) and prolapse in 22 (47.8%).
      Surgical technique included commissuroplasty (22, 47.8%), leaflet remodelling
      (17, 37.0%), decalcification (7, 15.2%) and raphe removal (14, 30.4%). At follow
      up, rest/stress echocardiography median AV regurgitation (rest 1.0 vs. stress
      1.0) and mean indexed AV area (IAVA) (rest 2.6 +/- 0.74 cm(2)/m(2) vs. stress 2.8
      +/- 0.4 cm(2)/m(2)) were unchanged (P = ns). Mean (rest 4.7 +/- 3.9 mmHg vs.
      stress 9.7 +/- 5.8 mmHg) and peak (rest 9.5 +/- 7.2 mmHg vs. stress 19.0 +/- 10.5
      mmHg) transvalvular gradients were significantly increased (P < 0.0001). At
      linear regression, there was an independent inverse correlation between
      commissuroplasty and AV gradients during stress (B = -9.9, P = 0.01, confidence
      interval= -17.7 to -2.1). Although follow-up haemodynamics of repaired AVs are
      satisfactory, there was a fixed IAVA and significant increase in AV gradients. We
      were not able to identify any pre-existing anatomical condition independently
      related to this non-physiological behaviour under stress. Moreover,
      commissuroplasty seems to prevent abnormal increase of the AV gradients.

PMID- 22368110
TI  - Wellness: the overlooked intervention for individuals with psychosis in the
      Kingdom of Bahrain.

PMID- 22368111
TI  - Early detection of lung inflammation: exploiting T1-effects of iron oxide
      particles using UTE MRI.
AB  - At high magnetic fields diagnostic proton MRI of the lung is problematic, because
      of fast T2* relaxation. The application of superparamagnetic contrast agents and
      the exploitation of the corresponding T2* effect is inefficient with conventional
      MRI methods, which limits the early detection of lung diseases. However, a simple
      theoretical treatment shows that in the lung, by the use of ultra-short echo time
      sequences, T2* effects can be neglected while T(1) shortening effects can be used
      for signal detection. In our study, we have applied a theoretically and
      experimentally optimized 3D ultra-short echo time sequence to lung phantoms and
      to a mouse model of lung inflammation, which was induced by systemic bacterial
      infection. Following the systemic application of very small superparamagnetic
      iron oxide nanoparticles, a significant signal increase in the lung of infected
      animals was detected already at 24 h postinfection, compared to control mice
      (17%, P < 0.001). Iron accumulation in the lung parenchyma as consequence of the
      host immune response was histologically confirmed. By conventional T2*- and T(2)
      weighted imaging, neither structural changes nor formation of substantial edema
      were observed.

PMID- 22368112
TI  - Label-free live-cell imaging of nucleic acids using stimulated Raman scattering
      microscopy.
AB  - Imaging of nucleic acids is important for studying cellular processes such as
      cell division and apoptosis. A noninvasive label-free technique is attractive.
      Raman spectroscopy provides rich chemical information based on specific
      vibrational peaks. However, the signal from spontaneous Raman scattering is weak
      and long integration times are required, which drastically limits the imaging
      speed when used for microscopy. Coherent Raman scattering techniques, comprising
      coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering
      (SRS) microscopy, overcome this problem by enhancing the signal level by up to
      five orders of magnitude. CARS microscopy suffers from a nonresonant background
      signal, which distorts Raman spectra and limits sensitivity. This makes CARS
      imaging of weak transitions in spectrally congested regions challenging. This is
      especially the case in the fingerprint region, where nucleic acids show
      characteristic peaks. The recently developed SRS microscopy is free from these
      limitations; excitation spectra are identical to those of spontaneous Raman and
      sensitivity is close to shot-noise limited. Herein we demonstrate the use of SRS
      imaging in the fingerprint region to map the distribution of nucleic acids in
      addition to proteins and lipids in single salivary gland cells of Drosophila
      larvae, and in single mammalian cells. This allows the imaging of DNA
      condensation associated with cell division and opens up possibilities of imaging
      such processes in vivo.

PMID- 22368113
TI  - Evaluation of a novel powered gait orthosis for walking by a spinal cord injury
      patient.
AB  - BACKGROUND: The aim of this case study was to analyze the effect on gait
      parameters of a new design of powered gait orthosis which applied synchronized
      motions to both the hip and knee joints when utilized for walking by a spinal
      cord injury (SCI) patient. CASE DESCRIPTION AND METHODS: Two orthoses were
      evaluated while worn by an incomplete SCI subject. Gait evaluation was performed
      when walking with an isocentric reciprocating gait orthosis (IRGO) and compared
      to that demonstrated by a newly developed powered version. This new orthosis was
      based on the IRGO superstructure but incorporated powered hip and knee joints
      using electrically motorized actuators. FINDINGS AND OUTCOMES: These gait
      parameters were improved when compared to standard IRGO and initial testing with
      the orthosis with only the hip or the knee joints activated in isolation. Maximum
      hip flexion and extension angles, as well as the maximum knee flexion and
      extension angles all increased when walking with the powered RGO compared to the
      IRGO. CONCLUSIONS: Gait evaluation of this newly developed orthosis showed
      improvement in measured parameters when compared to walking with an IRGO.
      Clinical relevance This case study gave the authors confidence to extend the
      research to a more extensive study with a group of SCI patients.

PMID- 22368114
TI  - Effect of ionic liquid additives to mobile phase on separation and system
      efficiency for HPLC of selected alkaloids on different stationary phases.
AB  - The silica-based stationary phases with favorable physical characteristics are
      the most popular in liquid chromatography. However, there are several problems
      with silica-based materials: severe peak tailing in the chromatography of basic
      compounds, non-reproducibility for the same chemistry columns, and limited pH
      stability. Ionic liquids (ILs) as mobile phase components can reduce peak tailing
      by masking residual free silanol groups. The chromatographic behavior of some
      alkaloids from different classes was studied on C18, phenyl, and
      pentafluorophenyl columns with different kinds and concentrations of ionic
      liquids as additives to aqueous mobile phases. Ionic liquids with different alkyl
      substituents on different cations or with different counterions as eluent
      additives were investigated. The addition of ionic liquids has great effects on
      the separation of alkaloids: decrease in band tailing, increase in system
      efficiency, and improved resolution. The retention, separation selectivity, and
      sequence of alkaloid elution were different when using eluents containing various
      ILs. The increase of IL concentration caused an increase in silanol blocking,
      thus conducted to decrease the interaction between alkaloid cations and free
      silanol groups, and caused a decrease of alkaloids retention, improvement of peak
      symmetry, and increase of theoretical plate number in most cases. The effect of
      ILs on stationary phases with different properties was also examined. The
      different properties of stationary phases resulted in differences in analyte
      retention, separation selectivity, peak shape, and system efficiency. The best
      shape of peaks and the highest theoretical plate number for most investigated
      alkaloids in mobile phases containing IL was obtained on pentafluorophenyl (PFP)
      phase.

PMID- 22368115
TI  - High performance liquid chromatography determination of fatty acids in drying
      oils following lipase action.
AB  - This paper describes a quantitative analytical procedure to determine the fatty
      acid composition in drying oils like linseed, walnut and poppy seed. The
      procedure required the enzymatic hydrolysis of the oil triacylglycerol families
      by the action of Candida rugosa lipase. The fatty acids (FFAs) produced
      (linolenic, myristic, linoleic, palmitic, oleic and stearic) were extracted with
      n-heptane and derivatized with alpha-bromoacetophenone. Their separation and
      quantitative determination were performed by high-performance liquid
      chromatography employing a C18 column and an isocratic elution method coupled to
      ultraviolet detection. The analytical enzymatic procedure is sensitive for < 0.5
      ug/mL of FFAs in a reduced sample of 0.1 mg of drying oil.

PMID- 22368116
TI  - Making ecosystem reality checks the status quo.

PMID- 22368120
TI  - Facile preparation of polymeric dimers from amphiphilic patchy particles.
AB  - A straightforward strategy for assembling polymeric dimers from amphiphilic
      nanoparticles is reported. Amphiphilic polymeric nanoparticles with a mixed-shell
      of PEO/P2VN blocks and a flexible core of PAA blocks are fabricated by a non
      covalent crosslinking method. Uniform polymeric dimers are efficiently and simply
      obtained via hydrophobic interactions under optimized conditions in selective
      solvent. The steric hindrance generated by reorganization of hydrophilic polymer
      brushes during the interparticle association is critical for morphological
      selectivity in the assembly. General applicability offers the possibility to
      organize functional NPs into superstructures with well-defined geometry and
      association numbers.

PMID- 22368121
TI  - The role of preoperative self-efficacy in predicting outcome after total knee
      replacement.
AB  - OBJECTIVES: The aim of the present study was to determine if self-efficacy is a
      significant and independent preoperative predictor of patient-reported pain and
      function at one year after total knee replacement (TKR). METHODS: Patients listed
      for a primary TKR because of osteoarthritis were recruited from preoperative
      assessment clinics at one regional orthopaedic centre. Before surgery, patients
      completed the Western Ontario and McMasters Osteoarthritis Index (WOMAC) Pain and
      Function Scale, Pain Self-Efficacy Scale, the Hospital Anxiety and Depression
      Scale, the Self-Administered Co-morbidity Questionnaire and questions about other
      painful joints. Patients then completed the WOMAC Pain and Function Scales at one
      year postoperatively. Regression analysis was performed to determine if self
      efficacy was a significant predictor of outcome after TKR. RESULTS: Overall, 251
      patients were recruited into this study, and one-year questionnaire data were
      available for 220 patients. At one year postoperatively, 7% of patients reported
      severe pain in their replaced knee and 9% reported severe functional limitations.
      Self-efficacy was found to be a significant preoperative predictor of functional
      ability, but not pain, at one year postoperatively, after controlling for age,
      gender, depression, anxiety, number of medical co-morbidities, preoperative knee
      status and painful joints elsewhere. Significant predictors of postoperative pain
      were greater anxiety and higher pain severity. Other significant predictors of
      postoperative disability were greater anxiety, worse functional disability and a
      greater number of painful joints elsewhere. CONCLUSIONS: The present study
      demonstrated that self-efficacy is a significant preoperative predictor of
      patient-reported functional ability at one year after TKR. Future research is
      needed to assess the impact of interventions for enhancing self-efficacy on
      patient-reported outcomes after TKR.

PMID- 22368122
TI  - Nutritive value of diets containing fish silage for juvenile Litopenaeus vannamei
      (Bonne, 1931).
AB  - BACKGROUND: Fish wastes has been used for many years as an alternative in feeds
      for aquaculture. In the present study weight gain of juvenile white shrimp
      Litopenaeus vannamei fed diets including fish waste silage (WS), fish waste
      silage with soybean meal SBM (WS + S) or fish waste meal (WM) was compared. A
      conventional acidic silage process was applied to obtain from wastes (skin,
      heads, bones and viscera) of snapper (Lutjanus spp.), grunt (Haemulon plumieri),
      and grouper (Epinephelus spp.) an ingredient rich in protein. RESULTS: After 3
      days ensilage more than 90% protein was hydrolysed. Waste material processed at
      pH 3.8 lost about 24% tryptophan. Butylated hydroxytoluene (BHT) prevented lipid
      oxidation, as shown after 45 days with malonaldehyde production. Shrimp fed WS +
      S diet gained 0.7 g per week higher than those fed WS and WM diets with 0.3 g per
      week (P < 0.05). CONCLUSION: WS processed with formic acid under conditions of
      low pH is beneficial for the white shrimp L. vannamei. It sustained reasonable
      weight gain combined with soybean meal in practical diets. On the other hand, BHT
      addition was beneficial in preventing oxidative action during silage preparation.

PMID- 22368123
TI  - Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast
      activity.
AB  - BACKGROUND: Arrhythmogenic ventricular remodeling is hallmarked by both reduced
      gap junction expression and increased collagen deposition. We hypothesized that
      reduced connexin43 (Cx43) expression is responsible for enhanced fibrosis in the
      remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we
      investigated the effect of normal or reduced Cx43 expression on the formation of
      fibrosis in a physiological (aging) and pathophysiological (transverse aortic
      constriction [TAC]) mouse model. METHODS AND RESULTS: The Cx43(fl/fl) and
      Cx43(CreER(T)/fl) mice were aged 18 to 21 months or, at the age of 3 months,
      either TAC or sham operated and euthanized after 16 weeks. Epicardial activation
      mapping of the right and left ventricles was performed on Langendorff perfused
      hearts. Sustained ventricular arrhythmias were induced in 0 of 11 aged
      Cx43(fl/fl) and 10 of 15 Cx43(Cre-ER(T)/fl) mice (P<0.01). Cx43 expression was
      reduced by half in aged Cx43(CreER(T)/fl) compared with aged Cx43(fl/fl) mice,
      whereas collagen deposition was significantly increased from 1.1+/-0.2% to 7.4+/
      1.3%. Aged Cx43(CreER(T)/fl) mice with arrhythmias had significantly higher
      levels of fibrosis and conduction heterogeneity than aged Cx43(CreER(T)/fl) mice
      without arrhythmias. The TAC operation significantly increased fibrosis in
      control compared with sham (4.0+/-1.2% versus 0.4+/-0.06%), but this increase was
      significantly higher in Cx43(CreER(T)/fl) mice (10.8+/-1.4%). Discoidin domain
      receptor 2 expression was unchanged, but procollagen peptide I and III expression
      and collagen type 1alpha2 mRNA levels were higher in TAC-operated Cx43HZ mice.
      CONCLUSIONS: Reduced cellular coupling results in more excessive collagen
      deposition during aging or pressure overload in mice due to enhanced fibroblast
      activity, leading to increased conduction in homogeneity and proarrhythmia.

PMID- 22368124
TI  - Shear wave imaging of the breast: still on the learning curve.

PMID- 22368125
TI  - Positional calibration of an ultrasound image-guided robotic breast biopsy
      system.
AB  - OBJECTIVES: Precision biopsy of small lesions is essential in providing high
      quality patient diagnosis and management. Localization depends on high-quality
      imaging. We have developed a dedicated, fully automatic volume breast ultrasound
      (US) imaging system for early breast cancer detection. This work focuses on
      development of an image-guided robotic biopsy system that is integrated with the
      volume breast US system for performing minimally invasive breast biopsies. The
      objective of this work was to assess the positional accuracy of the robotic
      system for breast biopsy. METHODS: We have adapted a compact robotic arm for
      performing breast biopsy. The arm incorporates a force torque sensor and is
      modified to accommodate breast biopsy sampling needles mounted on the robot end
      effector. Volume breast US images are used as input to a targeting algorithm that
      provides the physician with control of biopsy device guidance and trajectory
      optimization. In this work, the positional accuracy was evaluated using (1) a
      light-emitting diode (LED) mounted on the end effector and (2) a LED mounted on
      the end of a biopsy needle, each of which was imaged for each robot controller
      position as part of mapping the positional accuracy throughout a volume that
      would contain the breast. We measured the error in each location and the
      cumulative error. RESULTS: Robotic device performance over the volume provided
      mean accuracy +/- SD of 0.76 +/- 0.13 mm (end effector) and 0.55 +/- 0.13 mm
      (needle sample location), sufficient for a targeting accuracy within +/-1 mm,
      which is suitable for clinical use. Depth positioning error also was small: 0.38
      +/- 0.03 mm. Reproducibility was excellent with less than 0.5% variation.
      CONCLUSIONS: Overall accuracy and reproducibility of the compact robotic device
      were excellent, well within clinical biopsy performance requirements. Volume
      breast US data provide high-quality input to a biopsy sampling algorithm under
      physician control. Robotic devices may provide more precise device placement,
      assisting physicians with biopsy procedures.

PMID- 22368126
TI  - Parametric subharmonic imaging using a commercial intravascular ultrasound
      scanner: an in vivo feasibility study.
AB  - OBJECTIVES: The feasibility of visualizing atherosclerotic plaque using
      parametric subharmonic intravascular ultrasound (IVUS) was investigated in vivo.
      METHODS: Atherosclerosis was induced in the aorta of 2 rabbits. Following
      injection of Definity (Lantheus Medical Imaging, North Billerica, MA),
      radiofrequency IVUS signals were acquired at 40 MHz with a Galaxy IVUS scanner
      (Boston Scientific/Scimed, Natick, MA). Subharmonic imaging (SHI; receiving at 20
      MHz) was performed offline by applying an 8-order equalization filter. Contrast
      to-tissue ratios (CTRs) were computed for the vessel relative to the plaque area
      over 4 time points. Contrast-to-tissue ratios were also calculated for the plaque
      tissue and vessel-tissue from 4 tissue regions of interest at 4 time points.
      Finally, parametric images showing the cumulative maximum intensity (CMI), time
      to peak, perfusion (PER), and time-integrated intensity (TII) were generated for
      the fundamental and subharmonic data sets, and CTR measurements were repeated.
      RESULTS: Injection of the contrast agent resulted in improved delineation between
      plaque and the vessel lumen. Subharmonic imaging resulted in noticeable tissue
      suppression, although the intensity from the contrast agent was reduced. No
      significant improvement in the plaque to vessel lumen CTR was observed between
      the subharmonic and fundamental IVUS (2.1 +/- 3.64 versus 2.2 +/- 4.20; P = .5).
      However, the CTR for plaque-tissue was improved (11.8 +/- 7.32 versus 9.9 +/-
      7.06; P < .0001) for SHI relative to fundamental imaging. Cumulative-maximum
      intensity and TII maps of both fundamental and subharmonic data provided
      increased CTRs relative to nonparametric data sets (P < .002). Additionally, the
      CMI, PER, and TII of SHI IVUS showed significantly improved vessel-plaque CTRs
      for SHI relative to the fundamental (P < .04). CONCLUSIONS: Parametric SHI IVUS
      of atherosclerotic plaque is feasible and improves the visualization of the
      plaque.

PMID- 22368127
TI  - Usefulness of arrival time parametric imaging in evaluating the degree of liver
      disease progression in chronic hepatitis C infection.
AB  - OBJECTIVE: To determine whether the degree of liver disease progression in
      chronic hepatitis C infection can be evaluated by arrival time parametric imaging
      using contrast-enhanced sonography with Sonazoid (perfluorobutane; GE Healthcare,
      Oslo, Norway). METHODS: In this study, 60 patients with liver disease in chronic
      hepatitis C infection were examined and compared with 10 healthy volunteers who
      served as controls. A recommended dose of the sonographic contrast agent Sonazoid
      was intravenously infused, and the S5 or S6 region of the liver and right kidney
      were observed concurrently while movies of the procedure were saved. Arrival time
      parametric images of liver parenchymal blood flow were created, with red pixels
      to indicate an arrival time of 0 to 5 seconds and yellow pixels to indicate an
      arrival time of 5 to 10 seconds. From the obtained images, the ratio of the red
      area to the entire enhanced area of the liver was calculated using image
      processing software. Each participant was subsequently subjected to liver biopsy
      for liver fibrosis staging according to Metavir scores, and the determined
      fibrosis stage was compared with the ratio of red. The serum albumin level,
      platelet count, and prothrombin time were also compared with the ratio of red for
      each participant. RESULTS: The ratio of red increased significantly as liver
      fibrosis stage advanced (P < .01 for F1 versus F2; P < .01 for F1 versus F3; P <
      .01 for F1 versus F4; and P < .01 for F2 versus F4). As the ratio of red
      increased, significant decreases were observed in the serum albumin level (r = 
      0.29; P = .027), platelet count (r = -0.46; P = .0003), and prothrombin time (r =
      -0.46; P = .0002). CONCLUSIONS: Arrival time parametric imaging using Sonazoid
      enhanced sonography enables noninvasive evaluation of the degree of progression
      of liver disease in chronic hepatitis C infection and is thus considered
      clinically useful.

PMID- 22368128
TI  - Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia:
      prevalence and sonographic, hormonal, and seminal characteristics.
AB  - OBJECTIVE: Testicular adrenal rest tumors have been described in patients with
      congenital adrenal hyperplasia (CAH). The aim of this work was to (1) evaluate
      the prevalence of testicular adrenal rest tumors in patients with CAH; (2) study
      the hormonal profile; (3) define the sonographic features; (4) assess the seminal
      profile; and (5) initiate a longitudinal study on the possible role of
      corticotropin (ACTH) plasma levels in the induction and persistence of testicular
      adrenal rest tumors. METHODS: Eighteen patients affected by CAH, aged 21 to 41
      years, were studied. These were all patients referred to our endocrinology unit
      for the first time to undergo a clinical evaluation. All of the patients were
      taking long-term cortisone acetate and fludrocortisone replacement therapy. The
      study included (1) a physical examination, (2) testis sonography, (3) a hormonal
      profile, (4) semen analysis. RESULTS: Sonography showed testicular adrenal rest
      tumors in 11 patients (61.1%); of these, 9 cases (50.0%) were bilateral, and 2
      (11.1%) were unilateral. The diameter ranged from 4 to 38 mm. In 9 patients, the
      lesions were hypoechoic, whereas in 2, they were hyperechoic. High plasma ACTH
      levels were detected in all of the patients with tumors despite long-term
      therapy. Semen analysis found 2 cases of azoospermia and 6 cases of
      oligoasthenoteratozoospermia; the 3 remaining patients were normospermic. The
      preliminary longitudinal study has shown 3 patients with a disappearance or
      reduction of the tumors after 6 months of modified treatment. CONCLUSIONS: This
      study confirms the high prevalence of testicular adrenal rest tumors in patients
      with CAH and the major role played in its pathogenesis by high plasma ACTH
      levels.

PMID- 22368129
TI  - Congenital cardiac anomalies: prenatal readings versus neonatal outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine the variation between
      prenatal and postnatal diagnosis of congenital cardiac lesions diagnosed by both
      fetal center primary physicians and fetal pediatric cardiologists at a single
      tertiary referral center in the United States and evaluate why cases were
      misdiagnosed. METHODS: A retrospective review of all cardiac abnormalities
      identified prenatally by level II sonography at a tertiary referral fetal center
      between January 2006 and December 2008 was performed to include any patient with
      a fetal cardiac abnormality and with a documented autopsy or neonatal follow-up.
      Congenital heart disease diagnoses were classified as correct, incorrect, or
      incorrect but within the same spectrum of disease. Cases of correct diagnosis by
      primary physicians and pediatric cardiologists were compared. RESULTS: Sixty
      patients with fetal heart abnormalities were identified among 8894 patients who
      had level II sonography. The combined detection rate for fetal heart
      abnormalities for both primary physicians and pediatric cardiologists together
      was 81.7%. The detection rates of congenital heart disease were not statistically
      different between primary physicians and pediatric cardiologists: 77.9% (46 of
      59) versus 85.0% (34 of 40; P = .3). The most common cardiac abnormalities
      misdiagnosed in our study population included pulmonic stenosis, ventricular
      septal defect, myxoma, truncus arteriosus, and coarctation of the aorta.
      CONCLUSIONS: Congenital heart disease is misdiagnosed in tertiary care centers by
      both pediatric cardiologists and fetal imaging specialists. We believe that this
      occurrence is related to multiple factors, including evolution of congenital
      heart disease, maternal body habitus, associated congenital anomalies, decreased
      amniotic fluid volume, gestational age at evaluation, imaging techniques, and,
      most importantly, the experience of the sonographer.

PMID- 22368130
TI  - Persistent cloaca: a 10-year review of prenatal diagnosis.
AB  - OBJECTIVE: The purpose of this study was to review antenatal sonographic findings
      in children born with persistent cloaca. METHODS: Infants (n =145) with
      persistent cloaca followed at a center for colorectal congenital anomalies were
      identified by a retrospective chart review. Fifty female infants with a
      persistent cloaca met inclusion criteria and had prenatal records and imaging
      studies available for review. Sonographic data were retrospectively abstracted
      from charts. RESULTS: Anomalies were detected in 27 of 50 cases (54%). A correct
      antenatal diagnosis of persistent cloaca occurred in 3 of 50 (6%). Common
      findings misinterpreted on antenatal sonography include urinary tract anomalies,
      dilated bowel, and a cystic pelvic mass (representing hydrocolpos). CONCLUSIONS:
      Antenatal diagnosis of persistent cloaca is difficult. Persistent cloaca should
      be considered in the differential diagnosis if urinary tract malformations,
      dilated bowel loops, or cystic pelvic masses are visualized by prenatal
      diagnosis.

PMID- 22368131
TI  - Fetal transient clitoromegaly and transient hypertrophy of the labia minora in
      early and mid pregnancy.
AB  - OBJECTIVE: The purpose of this study was to describe a series of cases of
      transient changes in the female fetal external genitalia. METHODS: In our
      practice area, most pregnant women usually undergo a detailed sonographic survey
      of all fetal organs, including the external genitalia in early and mid pregnancy.
      RESULTS: During the study period (1987-2010), 62,145 consecutive pregnant women
      were scanned. We detected 4 fetuses with an isolated finding of clitoromegaly at
      15 to 16 weeks' gestation, which disappeared at 22 to 26 weeks. Maternal hormonal
      study results were normal. There was 1 case of clitoromegaly and a cloacal
      anomaly at 15 weeks' gestation, in which the clitoris retuned to a normal size at
      22 weeks. In addition, there were 3 cases of hypertrophy of the labia minora in
      early pregnancy, which disappeared at 26 to 32 weeks. All fetuses in these series
      had a normal XX karyotype and normal external genitalia at birth. CONCLUSIONS:
      Transient changes in the appearance of the fetal external genitalia may occur in
      chromosomally normal female fetuses.

PMID- 22368132
TI  - Sonographically guided intrasheath percutaneous release of the first annular
      pulley for trigger digits, part 1: clinical efficacy and safety.
AB  - OBJECTIVES: For trigger digits, intrasheath sonographically guided first annular
      (A1) pulley release has shown safety and effectiveness in cadavers. This clinical
      study describes sonographically guided A1 pulley release results in terms of
      resolution of symptoms, safety, and functional recovery. METHODS: Sonographically
      guided A1 pulley release (11-MHz probe) was used in 48 digits of 48 patients
      prospectively followed for 11.3 months and examined 1, 3, and 6 weeks, 3 and 6
      months, and 1 year later. Resolution of triggering (primary variable of interest)
      was expressed as the "success rate" per digit. The time for taking postoperative
      pain killers, range of motion recovery, grip strength, QuickDASH test scores,
      return to normal activities (including work), cosmetic results, satisfaction, and
      complications were assessed. RESULTS: The success rate was 100%, and no cases
      recurred. Mean times were 1.9 days for taking pain killers, 6.6 days for
      returning to normal activities, and 9.9 and 3.8 days for complete extension and
      flexion recovery, respectively. Mean QuickDASH scores were 39.8 preoperatively
      and 7.8, 1.7, and 0 after 6 weeks, 6 months, and 1 year postoperatively. Grip
      strength reached greater than 90% of the individual's normal strength by the
      sixth week in men and by the third month in women (P < .001). Radial digital
      nerve numbness developed in 1 finger, which disappeared by the third week. No
      other complications were noted. All wounds were cosmetically excellent, and final
      satisfaction was excellent or good in 98%. CONCLUSIONS: With adequate anatomic
      knowledge, technical training, and a basic ultrasound machine, sonographically
      guided A1 pulley release can be performed safely and successfully, offering an
      alternative to classic open surgery in the ambulatory setting.

PMID- 22368133
TI  - Sonographically guided intrasheath percutaneous release of the first annular
      pulley for trigger digits, part 2: randomized comparative study of the economic
      impact of 3 surgical models.
AB  - OBJECTIVES: Trigger digit surgery can be performed by an open approach using
      classic open surgery, by a wide-awake approach, or by sonographically guided
      first annular pulley release in day surgery and office-based ambulatory settings.
      Our goal was to perform a turnover and economic analysis of 3 surgical models.
      METHODS: Two studies were conducted. The first was a turnover analysis of 57
      patients allocated 4:4:1 into the surgical models: sonographically guided-office
      based, classic open-day surgery, and wide-awake-office-based. Regression analysis
      for the turnover time was monitored for assessing stability (R(2) < .26). Second,
      on the basis of turnover times and hospital tariff revenues, we calculated the
      total costs, income to cost ratio, opportunity cost, true cost, true net income
      (primary variable), break-even points for sonographically guided fixed costs, and
      1-way analysis for identifying thresholds among alternatives. RESULTS: Thirteen
      sonographically guided-office-based patients were withdrawn because of a learning
      curve influence. The wide-awake (n = 6) and classic (n = 26) models were compared
      to the last 25% of the sonographically guided group (n = 12), which showed
      significantly less mean turnover times, income to cost ratios 2.52 and 10.9 times
      larger, and true costs 75.48 and 20.92 times lower, respectively. A true net
      income break-even point happened after 19.78 sonographically guided-office-based
      procedures. Sensitivity analysis showed a threshold between wide-awake and last
      25% sonographically guided true costs if the last 25% sonographically guided
      turnover times reached 65.23 and 27.81 minutes, respectively. However, this trial
      was underpowered. CONCLUSIONS: This trial comparing surgical models was
      underpowered and is inconclusive on turnover times; however, the sonographically
      guided-office-based approach showed shorter turnover times and better economic
      results with a quick recoup of the costs of sonographically assisted surgery.

PMID- 22368134
TI  - Sonographic evaluation of anterosuperior hip labral tears with magnetic resonance
      arthrographic and surgical correlation.
AB  - OBJECTIVES: The purpose of this study was to retrospectively evaluate the
      sonographic findings compared with magnetic resonance (MR) arthrographic and
      arthroscopic findings in diagnosis of anterosuperior labral tears of the hip.
      METHODS: The Ethics Committees of our institution did not require patient
      approval or informed consent for this retrospective study. Sixteen symptomatic
      patients (4 male and 12 female; mean age, 43 years) with sonography, MR
      arthrography, and arthroscopy were enrolled. At arthroscopy, 11 patients were
      shown to have anterosuperior labral tears. We evaluated the findings of the
      anterosuperior acetabular labrum on sonography, with an emphasis on the presence
      or absence and types of labral tears, and correlated the findings with MR
      arthrography and arthroscopy. The types of tears were classified into radial
      flap, radial fibrillated, and longitudinal peripheral (base) tears. We calculated
      the sensitivity, specificity, and accuracy of sonography and MR arthrography.
      RESULTS: On sonography, 12 of 16 patients (75%) had a correct diagnosis of the
      presence or absence of an anterosuperior labral tear. On MR arthrography, 14 of
      16 patients (88%) had a correct diagnosis of the presence or absence of a tear.
      The sensitivity, specificity, and accuracy for the diagnosis of tears by
      sonography and MR arthrography were 82%, 60%, and 75% and 91%, 80%, and 88%,
      respectively. CONCLUSIONS: When the arthroscopic results were used as the
      reference standard, our preliminary study revealed that sonography managed to
      show anterosuperior labral abnormalities, although it had a lesser diagnostic
      ability than MR arthrography in diagnosing anterosuperior labral tears.
      Additional investigations including larger numbers of patients are required to
      determine whether sonography can be an alternative or adjunctive imaging
      technique for diagnosis of hip labral tears, especially in patients who decline
      or are unable to undergo MR arthrography.

PMID- 22368135
TI  - Comparative analysis of 2- versus 3-dimensional sonography of the supraspinatus
      tendon.
AB  - OBJECTIVES: The purpose of this study was to determine the reliability in the
      analysis of images acquired using a dedicated 3-dimensional (3D) ultrasound
      transducer and conventional 2-dimensional (2D) images in the detection and
      characterization of supraspinatus tendon tears. METHODS: Images of the
      supraspinatus tendon in 42 patients who had undergone 2D and 3D sonography were
      classified by two readers independently as no tear, full-thickness tear, or
      partial-thickness tear. When present, the tear size and location were recorded.
      Inter- and intra-rater reliability for the two data sets were calculated.
      RESULTS: There was substantial agreement between the two readers in the
      classification of supraspinatus tendon tears on 2D images (kappa = 0.79) but only
      moderate agreement on 3D images (kappa = 0.48). There was moderate to substantial
      agreement in the classification of tears between the 2D and 3D images for both
      readers (reader 1, kappa = 0.64; reader 2, kappa= 0.54). The most common cause of
      a discordant result was the interpretation of a small hypoechoic region at the
      footprint as a partial tear on 3D images, compared to a normal appearance on 2D
      images. CONCLUSIONS: Use of a dedicated 3D ultrasound transducer has poorer inter
      and intra-rater reliability for the assessment of supraspinatus tendon tears
      compared to 2D sonography because of the interpretation of small partial
      thickness tears at the footprint on 3D images, a common region affected by
      anisotropy.

PMID- 22368136
TI  - Teaching bedside sonography using peer mentoring: a prospective randomized trial.
AB  - OBJECTIVES: Bedside sonography is a growing field of medicine, but there is
      little evidence about how to teach it to medical students. A peer-mentoring
      system may help preclinical medical students learn bedside sonography. METHODS:
      In 2008 and 2009, participating first-year medical students completed an image
      recognition test at 0, 2, and 4 months and were randomized to an early or a late
      intervention group. In hands-on sessions, senior medical students taught the
      early intervention group how to perform a Trinity hypotensive ultrasound protocol
      between months 0 and 2 and then taught the late intervention group the Trinity
      protocol between months 2 and 4. Participants completed a practical examination
      at month 4. We measured the improvement in knowledge after the intervention and
      retention of knowledge and skills in the early intervention group at month 4.
      First-year medical students completed precourse and postcourse surveys about
      comfort and skills with sonography. RESULTS: Eighty-six first-year medical
      students enrolled; 79 completed the precourse survey; 54 completed all knowledge
      tests; 52 completed the practical examination; and 49 completed the postcourse
      survey. Of the 125 nonparticipants, 109 completed the precourse survey, and 25
      completed the postcourse survey. Participants' knowledge scores increased by 30%
      after the intervention. The early intervention group retained 92% of the
      knowledge gained. Thirty-six percent of participants were able to complete the
      Trinity protocol in 15 minutes during the practical examination, with no
      significant difference between the early and late intervention groups.
      Participants responded positively about the experience and indicated that hands
      on sessions were helpful. CONCLUSIONS: Peer mentoring is a useful method for
      teaching sonography to preclinical medical students.

PMID- 22368137
TI  - Cerebral blood flow in patients with Fabry disease as measured by Doppler
      sonography is not different from that in healthy individuals and is unaffected by
      treatment.
AB  - OBJECTIVES: The purpose of this study was to investigate cervical and cerebral
      blood flow characteristics in patients with Fabry disease at baseline and under
      enzyme replacement therapy. METHODS: In this case-control study we prospectively
      studied 68 patients with Fabry disease with extracranial and transcranial Doppler
      sonography. We compared extracranial and transcranial cervical and cerebral blood
      flow properties in all patients with Fabry disease and in subgroups of those with
      or without enzyme replacement therapy, male and female, and with normal or
      impaired renal function. Eight male patients were investigated at baseline and 1
      year after initiation of enzyme replacement therapy. RESULTS: We show that
      cervical and cerebral blood flow parameters in patients with Fabry disease are
      not different from normal values regardless of sex, renal function, or enzyme
      replacement therapy. CONCLUSIONS: Cervical and cerebral blood flow measured with
      extracranial and transcranial Doppler sonography is not altered in patients with
      Fabry disease. Enzyme replacement therapy does not change blood flow
      characteristics.

PMID- 22368138
TI  - Potential use of ultrasound speckle tracking for motion management during
      radiotherapy: preliminary report.
AB  - We prospectively evaluated real-time ultrasound speckle tracking for monitoring
      soft tissue motion for image-guided radiotherapy. Two human volunteers and 1
      patient with a proven hepatocellular carcinoma, who was being prepared for
      radiation therapy treatment, were scanned using a clinical ultrasound scanner
      modified to acquire and store radiofrequency signals. Scans were performed of the
      liver in the volunteers and the patient. In the patient, the speckle-tracking
      results were compared to those measured on a treatment-planning 4-dimensional
      computed tomogram with tumors contoured manually in each phase and with estimates
      made by hand on gray scale ultrasound images. The surface of the right lung and
      the prostate were scanned in a volunteer. The liver and lung surface were scanned
      during respiration. To simulate prostate motion, the ultrasound probe was rocked
      in an anterior-posterior direction. The correlation coefficients of all motion
      measurements were significantly correlated at all sites (P < .00001 for all
      sites) with 0 time delays. Ultrasound speckle-tracking motion estimates of tumor
      motion were within 2 mm of estimates made by hand tracking on gray scale
      ultrasound images and the 4-dimensional computed tomogram. The total tumor motion
      was greater than 20 mm. The angular displacement of the prostate was within 0.02
      radians (1.1 degrees ) with displacements measured by hand. Speckle tracking
      could be used to monitor organ motion during radiotherapy.

PMID- 22368139
TI  - Sonographic diagnosis of a subclinical wandering spleen: role of the decubitus
      position.
AB  - A wandering spleen is a rare condition. It is usually diagnosed when abdominal
      pain develops secondary to splenic torsion. Although splenic hypermobility is the
      pathognomonic feature of a wandering spleen, it is rarely revealed by imaging in
      the subclinical stage. We report 3 patients with a subclinical wandering spleen
      who had incidental sonographic findings of splenomegaly. Gray scale and color
      Doppler sonography in the right decubitus position can easily show the migratory
      nature and perfusion status of a wandering spleen in real time.

PMID- 22368140
TI  - Sonographic appearance of the submandibular glands in patients with
      immunoglobulin G4-related disease.
AB  - Swelling of the salivary glands is often an initial sign of immunoglobulin G4
      (IgG4)-related disease or IgG4-related sclerosing/autoimmune disease. We
      encountered 2 patients with IgG4-related disease who showed swollen submandibular
      glands with a unique characteristic sonographic pattern. Bilateral submandibular
      glands of both patients were enlarged with a smooth contour. The internal echo
      texture indicated multiple hypoechoic foci scattered against a heterogeneous
      background, which characteristically appeared with a mottled or irregular netlike
      appearance. A histopathologic examination of a resected section showed multiple
      foci of dense infiltrated lymphoplasmacytic cells and lymph follicles encircled
      by fibrous bands. A mottled appearance in the sonographic findings of the
      submandibular glands suggests the characteristic of IgG4-related disease and can
      be helpful in the differential diagnosis at the initial manifestation.

PMID- 22368141
TI  - Paralabral cysts of the hip: sonographic evaluation with magnetic resonance
      arthrographic correlation.
AB  - This retrospective study demonstrates the sonographic appearance paralabral cysts
      of the hip with magnetic resonance (MR) arthrography as the reference standard.
      Consensus review by 2 musculoskeletal radiologists was used to assess the
      paralabral cysts and determine their characteristics. The 3 paralabral cysts seen
      on sonography and confirmed with MR arthrography in this study were anechoic or
      hypoechoic, lobulated, and filled with contrast on MR imaging. A labral tear was
      also noted in all cases on both sonography and MR arthrography. Sonographic
      assessment for an anterior hip paralabral cyst and labral tear may be of
      diagnostic benefit.

PMID- 22368142
TI  - Think ultrasound when evaluating for pneumothorax.

PMID- 22368143
TI  - Bifid tongue, a rare congenital malformation, is a prenatal clue for secondary
      cleft palate.

PMID- 22368144
TI  - Segmental renal dysplasia presenting as a solid mass on sonography.

PMID- 22368145
TI  - Electromagnetic navigation platform for endovascular surgery: how to develop
      sensorized catheters and guidewires.
AB  - BACKGROUND: Endovascular procedures are nowadays limited by difficulties arising
      from the use of 2D images and are associated with dangerous X-ray exposure and
      the injection of nephrotoxic contrast medium. METHODS: An electromagnetic
      navigator is proposed to guide endovascular procedures with reduced radiation
      dose and contrast medium injection. Five DOF electromagnetic sensors are
      calibrated and used to track in real time the positions and orientation of
      endovascular catheters and guidewires, while intraoperative 3D rotational
      angiography is used to acquire 3D models of patient anatomy. A preliminary
      prototype is developed to prove the feasibility of the system using an
      anthropomorphic phantom. RESULTS: The spatial accuracy of the system was
      evaluated during 70 targeting trials obtaining an overall accuracy of 1.2 +/- 0.3
      mm; system usability was positively evaluated by three surgeons. CONCLUSIONS: The
      strategy proposed to sensorize endovascular instruments paves the way for the
      development of surgical strategies with reduced radiation dose and contrast
      medium injection. Further in vitro, animal and clinical experiments are necessary
      for complete surgical validation.

PMID- 22368146
TI  - Direct cyclodextrin-mediated ring opening polymerization of epsilon-caprolactone
      in the presence of yttrium trisphenolate catalyst.
AB  - Unmodified beta-cyclodextrin has been directly used to initiate ring-opening
      polymerization of epsilon-caprolactone in the presence of yttrium trisphenolate.
      Well-defined cyclodextrin (CD)-centered star-shaped poly(epsilon-caprolactone)s
      have been successfully synthesized containing definite average numbers of arms
      (N(arm) = 4-6) and narrow polydispersity indexes (below 1.10). The number-average
      molecular weight (M(n,NMR)) and average molecular weight per arm (M(n,arm)) are
      controlled by the feeding molar ratio of monomer to initiator. The prepared star
      PCL with M(n,NMR) of 2.7 * 10(3) is in fully amorphous and that with M(n,NMR) of
      13.3 * 10(3) is crystallized. In addition, the obtained poly(e-caprolactone)
      (PCL) stars with various molecular weights have different solubilities in
      methanol and tetrahydrofuran, which can be applied for further modifications.

PMID- 22368147
TI  - The effect of leptin on maturing porcine oocytes is dependent on glucose
      concentration.
AB  - Increased body weight is often accompanied by increased circulating levels of
      leptin and glucose, which alters glucose metabolism in various tissues, including
      perhaps the oocyte. Alteration of glucose metabolism impacts oocyte function and
      may contribute to the subfertility often associated with obese individuals. The
      objective of this study was to determine the effect of leptin (0, 10, and 100
      ng/ml) on the oocyte and cumulus cells during in vitro maturation under differing
      glucose concentrations. We examined the effects of leptin on oocyte maturation,
      blastocyst development, and/or gene expression in oocytes and cumulus cells
      (IRS1, IGF1, PPARgamma, IL6, GLUT1) in a physiological glucose (2 mM) and high
      glucose (50 mM) environment. We also evaluated the effect of leptin on glucose
      metabolism via glycolysis and the pentose phosphate pathway. In a physiological
      glucose environment, leptin did not have an influence on oocyte maturation,
      blastocyst development, or oocyte gene expression. Expression of GLUT1 in cumulus
      cells was downregulated with 100 ng/ml leptin treatment, but did not affect
      oocyte glucose metabolism. In a high glucose environment, oocyte maturation and
      glycolysis were decreased, but in the presence of 100 ng/ml leptin, these
      parameters were improved to levels similar to control. This effect is potentially
      mediated by an upregulation of oocyte IRS1 and a correction of cumulus cell IGF1
      expression. The present study demonstrates that in a physiological glucose
      concentration, leptin plays a negligible role in oocyte function. However, leptin
      appears to modulate the deleterious impact of a high glucose environment on
      oocyte function.

PMID- 22368148
TI  - Minimally invasive robotically assisted repair of atrial perforation from a
      pacemaker lead.
AB  - BACKGROUND: We present the first reported case of robotic-assisted right atrial
      perforation repair and pacemaker lead extraction. METHODS: A 75-year-old female
      with symptomatic sinus node dysfunction underwent atrial single chamber permanent
      pacemaker insertion via a persistent left superior vena cava approach. At one
      week follow-up a chest radiograph and a computerized dynamic tomography
      demonstrated that the right atrial lead had perforated the right atrial free
      wall. The patient remained asymptomatic without signs of pericardial tamponade,
      however urgent repair was warranted. RESULTS: Utilizing the da Vinci robotic
      system (Intuitive Surgical Inc., Sunnyvale, California, USA), the pacer lead
      perforation was visualized, the lead retracted, and the right atrium repaired.
      The existing atrial lead was repositioned in the right atrial appendage.
      CONCLUSION: The patient's postoperative convalescence was uneventful, and she was
      discharged home on the third post-operative day. This case demonstrates the
      increasing clinical utilization of robotic-assisted technology in minimally
      invasive cardiac surgery.

PMID- 22368149
TI  - Effect of PON1 Q192R genetic polymorphism on clopidogrel efficacy and
      cardiovascular events in the Clopidogrel in the Unstable Angina to Prevent
      Recurrent Events trial and the Atrial Fibrillation Clopidogrel Trial with
      Irbesartan for Prevention of Vascular Events.
AB  - BACKGROUND: A recent report suggested that carriers of the Q allele of the PON1
      Q192R polymorphism had decreased biotransformation of clopidogrel into its active
      metabolite and decreased efficacy of clopidogrel in preventing cardiovascular
      events. Furthermore, PON1 has been reported to have a central role in the
      antioxidant function of high-density lipoprotein, and the Q192R polymorphism has
      been previously associated with cardiovascular risk in patients not treated with
      clopidogrel. METHODS AND RESULTS: Patients (n=5059) from the Clopidogrel in
      Unstable Angina to Prevent Recurrent Events (CURE) randomized trial that
      demonstrated benefits of clopidogrel versus placebo in preventing cardiovascular
      events in acute coronary syndromes were genotyped for the PON1 Q192R
      polymorphism. Clopidogrel compared with placebo significantly reduced the first
      primary efficacy outcome, irrespective of PON1 Q192R genotype (P=0.07 for
      heterogeneity). No association was observed between the Q192R polymorphism and
      cardiovascular events in the overall sample (hazard ratio [HR], 1.09 per allele;
      95% confidence interval [CI], 0.95-1.24; P=0.23). However, an association was
      observed between the Q allele and increased cardiovascular events in the placebo
      group (HR, 1.23 per allele; 95% CI, 1.03-1.47; P=0.03) but not in the clopidogrel
      group (HR, 0.93 per allele; 95% CI, 0.76-1.13; P=0.46). In 1156 atrial
      fibrillation patients from the Atrial Fibrillation Clopidogrel Trial With
      Irbesartan for Prevention of Vascular Events, there was no evidence of
      interaction between PON1 genotype and clopidogrel for any outcome or for an
      association between genotype and cardiovascular events. CONCLUSIONS: In
      conclusion, our study shows that PON1 Q192R genotype does not modify the efficacy
      and safety of clopidogrel in patients with acute coronary syndromes. Further
      studies are needed to confirm or refute the association of the Q allele with
      adverse cardiovascular events independent of clopidogrel in secondary prevention
      patients.

PMID- 22368150
TI  - High ratio of resting energy expenditure to body mass in childhood and
      adolescence: a mechanistic model.
AB  - BACKGROUND: Children have lower resting energy expenditure (REE) but higher ratio
      of resting energy expenditure to body mass (REE/BM) than do adults. This well
      known observation has never been quantitatively explained. OBJECTIVES: The aim of
      the present study is to understand the high REE/BM in childhood and adolescence.
      DESIGN: A mechanistic REE/BM model is proposed. Literature data on REE, BM and
      the masses of four high metabolic rate organs (i.e., liver, brain, heart and
      kidneys) of 1-18 y boys and girls were used to evaluate the proposed REE/BM
      model. Specifically, we tested the hypothesis that the magnitude and variation of
      the REE/BM can be predicted by a combination of four variables, including
      relative cellularity, growth energy expenditure for constructing new cells,
      fraction of body mass as individual organs/tissues, and their specific resting
      energy expenditure. RESULTS: The REE/BM provided by the literature is 54 kcal/kg
      per day at 1 year, decreasing to 26.0 kcal/kg per day at 18 years. Model
      predicted REE/BM can account for 97.0% and 100.7% of the literature-reported
      REE/BM in males and females, respectively. The average differences between
      literature-reported and model-predicted REE/BM are 1.1 kcal/kg per day in boys
      and -0.3 kcal/kg per day in girls. CONCLUSION: The high REE/BM ratio in childhood
      results from two model variables: the high fraction of body mass as liver, brain,
      heart, and kidneys, and their high specific resting metabolic rates. The proposed
      REE/BM model promotes understanding of the REE, and allows a rational
      establishment of energy requirements for children and adolescents.

PMID- 22368151
TI  - Inducible Prrxl1-CreER(T2)  recombination activity in the somatosensory afferent
      pathway.
AB  - Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase
      were generated by modifying a Prrxl1-containing BAC clone. Cre recombination
      activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various
      embryonic and postnatal stages. Pregnant mice were treated with a single dose of
      tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2
      days later. Strong X-gal staining was observed in the somatosensory ganglia
      (e.g., dorsal root and trigeminal ganglia) and the first central sites for
      processing somatosensory information (e.g., spinal dorsal horn and trigeminal
      nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20
      or in adulthood (P120), strong Cre recombination activity was present in the
      primary somatosensory ganglia, while weak Cre recombination activity was found in
      the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory
      trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a
      useful tool for exploring genes' functions in the somatosensory system in a time
      controlled way.

PMID- 22368153
TI  - Diversity is what you want it to be: how social-dominance motives affect
      construals of diversity.
AB  - We propose that diversity is a malleable concept capable of being used either to
      attenuate or to enhance racial inequality. The research reported here suggests
      that when people are exposed to ambiguous information concerning an
      organization's diversity, they construe diversity in a manner consistent with
      their social-dominance motives. Specifically, anti-egalitarian individuals
      broaden their construal of diversity to include nonracial (i.e., occupational)
      heterogeneity when an organization's racial heterogeneity is low. By contrast,
      egalitarian individuals broaden their construal of diversity to include nonracial
      heterogeneity when an organization's racial heterogeneity is high. The inclusion
      of occupational heterogeneity in perceptions of diversity allows people across
      the spectrum of social-dominance orientation to justify their support for or
      opposition to hierarchy-attenuating affirmative-action policies. Our findings
      suggest that diversity may not have a fixed meaning and that, without a specific
      delineation of what the concept means in particular contexts, people may construe
      diversity in a manner consistent with their social motivations.

PMID- 22368152
TI  - Effects of catecholamine stress on diastolic function and myocardial energetics
      in obesity.
AB  - BACKGROUND: Obesity is characterized by impaired cardiac energetics, which may
      play a role in the development of diastolic dysfunction and inappropriate
      shortness of breath. We assessed whether, in obesity, derangement of energetics
      and diastolic function is further altered during acute cardiac stress. METHODS
      AND RESULTS: Normal-weight (body mass index, 22+/-2 kg/m(2); n=9-17) and obese
      (body mass index, 39+/-7 kg/m(2); n=17-46) subjects underwent assessment of
      diastolic left ventricular function (cine magnetic resonance imaging volume-time
      curve analysis) and cardiac energetics (phosphocreatine/ATP ratio; (31)P-magnetic
      resonance spectroscopy) at rest and during dobutamine stress (heart rate
      increase, 65+/-22% and 69+/-14%, respectively; P=0.61). At rest, obesity was
      associated with a 22% lower peak filling rate (P<0.001) and a 15% lower
      phosphocreatine/ATP ratio (1.73+/-0.40 versus 2.03+/-0.28; P=0.048). Peak filling
      rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio,
      and phosphocreatine/ATP ratio. On multivariable analysis, phosphocreatine/ATP was
      the only independent predictor of peak filling rate (beta=0.50; P=0.03). During
      stress, a further reduction in phosphocreatine/ATP occurred in obese (from 1.73+/
      0.40 to 1.53+/-0.50; P=0.03) but not in normal-weight (from 1.98+/-0.24 to 2.04+/
      0.34; P=0.50) subject. For similar levels of inotropic stress, there were smaller
      increases in peak filling rate in obesity (38% versus 70%; P=0.01). CONCLUSIONS:
      In obesity, cardiac energetics are further deranged during inotropic stress, in
      association with continued diastolic dysfunction. Myocardial energetics may play
      a key role in the impairment of diastolic function in obesity.

PMID- 22368154
TI  - The cost of callousness: regulating compassion influences the moral self-concept.
AB  - It has often been argued that compassion is fundamental to morality. Yet people
      often suppress compassion for self-interested reasons. We provide evidence that
      suppressing compassion is not cost free, as it creates dissonance between a
      person's moral identity and his or her moral principles. We instructed separate
      groups of participants to regulate their compassion, regulate their feelings of
      distress, or freely experience emotions toward compassion--inducing images.
      Participants then reported how central morality was to their identities and how
      much they believed that moral rules should always be followed. Participants who
      regulated compassion-but not those who regulated distress or experienced emotions
      -showed a dissonance-based trade-off. If they reported higher levels of moral
      identity, they had a greater belief that moral rules could be broken. If they
      maintained their belief that moral rules should always be followed, they
      sacrificed their moral identity. Regulating compassion thus has a cost of its
      own: It forces trade-offs within a person's moral self-concept.

PMID- 22368155
TI  - Preschools reduce early academic-achievement gaps: a longitudinal twin approach.
AB  - Preschools may reduce inequalities in early academic achievement by providing
      children from disadvantaged families with higher-quality learning environments
      than they would otherwise receive. In this study, longitudinal data from a
      nationally representative sample of more than 600 twin pairs were used to
      estimate the contributions of genes, the shared environment, and the nonshared
      environment to cognition and achievement scores in children enrolled versus not
      enrolled in preschool. Attending preschool at age 4 was associated with
      reductions in shared environmental influences on reading and math skills at age
      5, but was not associated with the magnitude of shared environmental influences
      on cognition at age 2. These prospective effects were mediated by reductions in
      achievement gaps associated with minority status, socioeconomic status, and
      ratings of parental stimulation of cognitive development. Lower socioeconomic
      status was associated with lower rates of preschool enrollment, which suggests
      that the very children who would benefit most from preschools are the least
      likely to be enrolled in them.

PMID- 22368157
TI  - Successful transplantation of small-for-size grafts: a reappraisal.

PMID- 22368156
TI  - Clinicopathologic study and outcome analysis of thyroid lymphomas: experience
      from a tertiary cancer center.
AB  - BACKGROUND: The aim of this study was to review clinicopathologic presentations
      of patients diagnosed with thyroid lymphomas at a tertiary cancer center. Thyroid
      lymphomas represent less than 2% of all lymphomas. METHODS: The lymphoma clinic
      database was retrospectively reviewed to collect information on patients
      diagnosed with thyroid lymphomas. Tissue microarrays were constructed in 37
      patients for evaluation of germinal center (CD10/bcl-6) and activated B-cell
      immunophenotype markers (FoxP1, Mum1). RESULTS: During 2000 to 2010, 64 of 5668
      patients registered at our lymphoma clinic were diagnosed with thyroid lymphoma
      (1.7%). Complete response (CR) to treatment was seen in 80.7%. The germinal
      center immunophenotype and activated B-cell immune phenotype did not influence
      the prognosis. FoxP1, however, was associated with poor treatment response and
      decreased survival. CONCLUSIONS: Advanced International Prognostic Index (IPI)
      score and combined-modality treatment emerged as significant prognostic factors
      for treatment response and overall survival. Immunophenotype expression of FoxP1
      carries a poor prognosis in diffuse large B-cell lymphoma as elsewhere.

PMID- 22368158
TI  - Looking into Pandora's box.

PMID- 22368159
TI  - Molecular pathways: digoxin use and estrogen-sensitive cancers--risks and
      possible therapeutic implications.
AB  - Digoxin, a phyto-estrogen, binds with estrogen receptors (ER) and can cause
      gynecomastia. Among women currently using digoxin, breast and uterus cancer
      incidences are significantly increased (approximate risk ratios, 1.3-1.5). Both
      cancers are often estrogen sensitive. In contrast, ovary and cervix cancers are
      relatively estrogen insensitive, and incidence is unaffected by digoxin exposure.
      When digoxin use stops, incidence rapidly reverts to that in nonusers. These
      patterns parallel those of estrogen, suggesting that digoxin works via ER
      stimulated proliferation of ductal and/or acinar cells, accelerating the growth
      of nascent cancers. Also consistent with an estrogenic effect, men using digoxin
      have a small but significant reduction in prostate cancer (risk ratio, 0.76).
      Other estrogen-like drugs, particularly spironolactone, should be investigated
      for similar effects. The effect of digoxin use in women being treated for breast
      cancer or in survivors is unknown. Women with estrogen-sensitive cancers on
      adjuvant therapy may take tamoxifen, which blocks ERs. However, postmenopausal
      patients may use aromatase inhibitors, which block estrogen production while
      leaving ERs susceptible to digoxin. If adverse effects are found, tamoxifen may
      be preferred over aromatase inhibitors in patients receiving estrogen-mimicking
      drugs. Alternatively, other cardiotropic drugs might be considered in women with
      or at high risk of developing estrogen-sensitive cancers.

PMID- 22368160
TI  - Preliminary evaluation of the reliability and validity of the Shame and Stigma
      Scale in head and neck cancer.
AB  - BACKGROUND: Facial disfigurement from head and neck cancer can lead to the
      development of shame and a perception of stigma. We sought to develop the Shame
      and Stigma Scale (SSS) to measure this. Items were administered to 104 patients
      with squamous cell carcinoma of the oral cavity, together with measures of
      quality of life and adaptation. Exploratory factor analysis and item response
      theory (IRT) models assessed its psychometric properties. RESULTS: A 20-item SSS
      had a Cronbach's alpha of 0.94 and 4 factors: shame with appearance, sense of
      stigma, regret, and speech/social concerns. These factors show satisfactory
      internal validity, convergent validity with the Functional Assessment of Cancer
      Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Head and
      Neck (FACT-H&N), Demoralization Scale and Patient Health Questionnaire (PHQ)
      Depression, and divergent validity with the Social Desirability Scale. The items
      displayed desirable properties in factor-specific (IRT) models. CONCLUSION:
      Further validation studies are worthwhile to confirm this factor structure,
      reliability, and validity, and generalizability to all head and neck cancers.

PMID- 22368161
TI  - The sex offender treatment intervention and progress scale (SOTIPS): psychometric
      properties and incremental predictive validity with static-99R.
AB  - The Sex Offender Treatment Intervention and Progress Scale (SOTIPS) is a 16-item
      rating scale designed to assess dynamic risk among adult male sex offenders and
      degree of change at 6-month intervals during treatment. The purpose of the
      present study was to examine the psychometric properties of the SOTIPS in a
      construction sample of 759 adult male sex offenders who were under correctional
      supervision and enrolled in cognitive-behavioral community treatment in Vermont
      between 2001 and 2007. The scale showed acceptable interrater reliability. SOTIPS
      scores at 1, 7, and 13 months after participants began treatment predicted
      sexual, violent, and any recidivism, and return to prison at fixed 1- and 3-year
      follow-up periods (AUCs = .60 to .85). Combined SOTIPS and Static-99R scores
      predicted all recidivism types (AUCs = .67 to .89) and outperformed either
      instrument alone when both instruments had similar predictive power. Participants
      who demonstrated treatment progress, as reflected by reductions in SOTIPS scores,
      showed lower rates of recidivism than those who did not.

PMID- 22368162
TI  - Causes of equine abortion, stillbirth and neonatal death in central Italy.

PMID- 22368163
TI  - Prevalence of respiratory signs and identification of risk factors for
      respiratory morbidity in Swedish Yorkshire terriers.
AB  - Yorkshire terriers may be prone to respiratory disease; however, limited
      epidemiological information is available. A cross-sectional study design was used
      to compare the prevalence of respiratory signs in Yorkshire terriers with the
      prevalence in a population of dogs in general and to identify risk factors for
      respiratory clinical signs within the Swedish population of Yorkshire terriers.
      Data on clinical signs and risk factors were obtained from a questionnaire. The
      prevalence of respiratory signs in general (RS) was significantly higher among
      Yorkshire terriers compared with control dogs (RS 56.3 per cent and 23.0 per
      cent), and likewise more frequent respiratory signs (FRS) (26.0 per cent and 5.0
      per cent). Age, sex and breed were shown to be significant risk factors, and an
      interaction between age and sex was discovered. The study indicated a sex ratio
      reversal in the prevalence of RS - the probability of females having RS increased
      with advancing age, while the probability for males was fairly constant.

PMID- 22368164
TI  - New method for removing mucus from the upper respiratory tract of newborn puppies
      following caesarean section.

PMID- 22368165
TI  - Use of rigid endoscopy to evaluate vaginal haemorrhage in a rat.

PMID- 22368167
TI  - Arcicella rigui sp. nov., isolated from water of a wetland, and emended
      descriptions of the genus Arcicella, Arcicella aquatica, Arcicella rosea and
      Arcicella aurantiaca.
AB  - A bacterial strain, designated NSW-5(T), was isolated from a water sample taken
      from Niao-Song Wetland Park in Taiwan and characterized using a polyphasic
      taxonomic approach. Cells of strain NSW-5(T) were strictly aerobic, Gram-stain
      negative, non-motile and polymorphic, being straight, vibrioid, curved and spiral
      shaped rods surrounded by a thick capsule and forming light pink-coloured
      colonies. Some rings consisting of several cells were present. Growth occurred at
      10-40  degrees C (optimum, 25  degrees C), with 0-3.0 % NaCl (optimum, 0 %) and
      at pH 6.0-8.0 (optimum, pH 7.0). Phylogenetic analyses based on 16S rRNA gene
      sequences showed that strain NSW-5(T) belonged to the genus Arcicella with
      sequence similarities of 98.6, 98.0 and 97.3 % with Arcicella aquatica NO-502(T),
      Arcicella rosea TW5(T) and Arcicella aurantiaca TNR-18(T), respectively. The
      predominant cellular fatty acids were summed feature 3 (C(16 : 1)omega7c and/or
      C(16 : 1)omega6c; 20.8 %), C(16 : 0) (14.6 %), iso-C(15 : 0) (13.8 %), C(16 :
      1)omega5c (12.5 %) and C(18 : 0) (11.4 %), and the only respiratory quinone was
      MK-7. The polar lipid profile consisted of phosphatidylethanolamine and several
      uncharacterized glycolipids, aminolipids, phospholipids and aminophospholipids.
      The DNA G+C content of strain NSW-5(T) was 44.1 mol%. The DNA-DNA relatedness of
      strain NSW-5(T) with respect to recognized species of the genus Arcicella was
      less than 70 %. On the basis of phylogenetic inference and phenotypic data,
      strain NSW-5(T) should be classified as a representative of a novel species, for
      which the name Arcicella rigui sp. nov. is proposed. The type strain is NSW-5(T)
      (= KCTC 23307(T) = BCRC 80260(T)). Emended descriptions of the genus Arcicella
      and of Arcicella aquatica, Arcicella rosea and Arcicella aurantiaca are also
      proposed.

PMID- 22368166
TI  - Myocardial ischemia reperfusion injury: from basic science to clinical bedside.
AB  - Myocardial ischemia reperfusion injury contributes to adverse cardiovascular
      outcomes after myocardial ischemia, cardiac surgery or circulatory arrest.
      Primarily, no blood flow to the heart causes an imbalance between oxygen demand
      and supply, named ischemia (from the Greek isch, restriction; and haema, blood),
      resulting in damage or dysfunction of the cardiac tissue. Instinctively, early
      and fast restoration of blood flow has been established to be the treatment of
      choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy
      or primary percutaneous coronary intervention is the most effective strategy for
      reducing the size of a myocardial infarct and improving the clinical outcome.
      Unfortunately, restoring blood flow to the ischemic myocardium, named
      reperfusion, can also induce injury. This phenomenon was therefore termed
      myocardial ischemia reperfusion injury. Subsequent studies in animal models of
      acute myocardial infarction suggest that myocardial ischemia reperfusion injury
      accounts for up to 50% of the final size of a myocardial infarct. Consequently,
      many researchers aim to understand the underlying molecular mechanism of
      myocardial ischemia reperfusion injury to find therapeutic strategies ultimately
      reducing the final infarct size. Despite the identification of numerous
      therapeutic strategies at the bench, many of them are just in the process of
      being translated to bedside. The current review discusses the most striking basic
      science findings made during the past decades that are currently under clinical
      evaluation, with the ultimate goal to treat patients who are suffering from
      myocardial ischemia reperfusion-associated tissue injury.

PMID- 22368168
TI  - Pseudovibrio axinellae sp. nov., isolated from an Irish marine sponge.
AB  - A Gram-negative, motile, rod-shaped bacterial strain, designated Ad2(T), was
      isolated from a marine sponge, Axinella dissimilis, which was collected from a
      semi-enclosed marine lake in Ireland. Strain Ad2(T) grew optimally at 24  degrees
      C, at pH 7.0 and in the presence of 3 % (w/v) NaCl. Phylogenetic analysis based
      on 16S rRNA gene sequences showed that strain Ad2(T) clustered with members of
      the genus Pseudovibrio, and showed 97.3-98.2 % sequence similarity to the type
      strains of recognized Pseudovibrio species. DNA-DNA relatedness values between
      strain Ad2(T) and the type strains of other Pseudovibrio species were <27 %. The
      DNA G+C content of strain Ad2(T) was 50.5 mol%. The major fatty acid was 18 :
      1omega7c. Differences in phenotypic properties, together with phylogenetic and
      DNA-DNA hybridization analyses, indicated that strain Ad2(T) represented a novel
      species of the genus Pseudovibrio. The name Pseudovibrio axinellae sp. nov. is
      proposed, with Ad2(T) (= DSM 24994(T) = NCIMB 14761(T)) as the type strain.

PMID- 22368169
TI  - Bdellovibrio exovorus sp. nov., a novel predator of Caulobacter crescentus.
AB  - The life cycle, prey range and taxonomic status of a Bdellovibrio-like organism,
      strain JSS(T), were studied. Strain JSS(T) was isolated from sewage in London,
      Ontario, Canada, in enrichment culture with Caulobacter crescentus prey cells.
      During predation, this strain remained attached to the outside of a stalked C.
      crescentus cell. No periplasmic growth stage was observed and no bdelloplast was
      formed. The stalked cells of C. crescentus retained their shape and, after
      predation, were devoid of cytoplasmic content, as shown by transmission electron
      microscopy. A periplasmic growth stage has been a definitive character in the
      description of members of the genera Bdellovibrio, Bacteriovorax, Bacteriolyticum
      and Peredibacter. This is the first description of an epibiotic predator in this
      group of prokaryotic predators. The G+C content of the genomic DNA of strain
      JSS(T) was 46.1 mol%. 16S rRNA gene sequence analysis showed that this strain was
      related to Bdellovibrio bacteriovorus strains HD100(T), 109J, 114 and 127 (90-93
      % similarity). Phylogenetic analysis based on 16S rRNA gene sequences grouped
      strain JSS(T) with the Bdellovibrio cluster, but at a distance from other
      Bdellovibrio isolates. On the basis of features of the life cycle and
      phylogenetic data, it was concluded that strain JSS(T) merits classification as
      the type strain of a novel species, for which the name Bdellovibrio exovorus sp.
      nov. is proposed (type strain JSS(T) =ATCC BAA-2330(T) = DSM 25223(T)).

PMID- 22368170
TI  - Brevibacterium daeguense sp. nov., a nitrate-reducing bacterium isolated from a 4
      chlorophenol enrichment culture.
AB  - A Gram-reaction-positive, non-spore-forming, aerobic actinobacterial strain (2C6
      41(T)) was isolated from the activated sludge from an industrial wastewater
      treatment plant in Daegu, South Korea. Its taxonomic position was investigated by
      using a polyphasic approach. On the basis of 16S rRNA gene sequence similarity,
      closest phylogenetic relatives to strain 2C6-41(T) were Brevibacterium
      pityocampae DSM 21720(T) (97.2 %), Brevibacterium salitolerans KCTC 19616(T)
      (96.7 %), Brevibacterium album KCTC 19173(T) (96.2 %) and Brevibacterium
      samyangense KCCM 42316(T) (96.2 %). The DNA G+C content of strain 2C6-41(T) was
      66.4 mol%. Chemotaxonomic data, which included MK-8(H(2)) as the major
      menaquinone; meso-diaminopimelic acid, glutamic acid and alanine as cell-wall
      amino acids; ribose, mannose and glucose as major cell-wall sugars; and anteiso
      C(15 : 0), anteiso-C(17 : 0), C(16 : 0) and iso-C(15 : 0) as major fatty acids,
      supported the affiliation of strain 2C6-41(T) to the genus Brevibacterium. The
      aromatic ring cleavage enzyme catechol 1,2-dioxygenase was not detected in strain
      2C6-41(T), but catechol 2,3-dioxygenase was detected. The results of
      physiological and biochemical tests, and the low level of DNA-DNA relatedness to
      the closest phylogenetic relative enabled strain 2C6-41(T) to be differentiated
      genotypically and phenotypically from recognized species of the genus
      Brevibacterium. The isolate is therefore considered to represent a novel species
      in the genus Brevibacterium, for which the name Brevibacterium daeguense sp. nov.
      is proposed. The type strain is 2C6-41(T) (=KCTC 19800(T) = JCM 17458(T)).

PMID- 22368171
TI  - Pullulanibacillus uraniitolerans sp. nov., an acidophilic, U(VI)-resistant
      species isolated from an acid uranium mill tailing effluent and emended
      description of the genus Pullulanibacillus.
AB  - Two Gram-positive-staining, rod-shaped, endospore-forming isolates (UG-2(T) and
      UG-3), with an optimum growth temperature of around 37  degrees C and an optimum
      pH for growth of about 4, were recovered from an acidic effluent of the uranium
      mill tailing at Urgeirica in Central Portugal. On the basis of 16S rRNA gene
      sequence similarity, the strains belonged to the family Sporolactobacillaceae and
      were closely related to Pullulanibacillus naganoensis ATCC 53909(T) (97.9 %).
      Unlike P. naganoensis, strains UG-2(T) and UG-3 grew in medium containing up to
      5000 p.p.m. U(VI) but did not hydrolyse pullulan. Chemotaxonomic data also
      supported the affiliation of strains UG-2(T) and UG-3 to the genus
      Pullulanibacillus. Physiological and biochemical tests along with fatty acid
      composition allowed differentiation of strains UG-2(T) and UG-3 from P.
      naganoensis. It is suggested that strains UG-2(T) and UG-3 represent a novel
      species, for which the name Pullulanibacillus uraniitolerans is proposed; the
      type strain is UG-2(T) (=DSM 19429(T) = LMG 24205(T)). An emended description of
      the genus Pullulanibacillus is also proposed.

PMID- 22368172
TI  - Pseudorhodoferax aquiterrae sp. nov., isolated from groundwater.
AB  - A Gram-negative, rod-shaped, motile, non-spore-forming and poly-beta
      hydroxybutyrate-containing bacterial strain, designated NAFc-7(T), was isolated
      from groundwater in Taiwan and was characterized using a polyphasic taxonomic
      approach. Growth occurred at 15-40  degrees C (optimum, 30  degrees C), at pH 6.0
      9.0 (optimum, pH 6.0-7.0) and with 0-3 % NaCl (optimum, 0-1 %). Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain NAFc-7(T), together
      with Pseudorhodoferax soli TBEA3(T) (98.2 % sequence similarity) and
      Pseudorhodoferax caeni SB1(T) (98.0 %), formed a deep line within the family
      Comamonadaceae. Strain NAFc-7(T) contained summed feature 3 (comprising C(16 :
      1)omega7c and/or C(16 : 1)omega6c), C(16 : 0) and C(17 : 0) cyclo as the
      predominant fatty acids. The major 3-hydroxy fatty acid was C(10 : 0) 3-OH. The
      major isoprenoid quinone was Q-8 and the DNA G+C content was 67.6 mol%. The polar
      lipid profile consisted of a mixture of phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylserine and an
      uncharacterized phospholipid. The DNA-DNA relatedness of strain NAFc-7(T) with
      respect to recognized species of the genus Pseudorhodoferax was less than 70 %.
      On the basis of the genotypic, chemotaxonomic and phenotypic data, strain NAFc
      7(T) represents a novel member of the genus Pseudorhodoferax, for which the name
      Pseudorhodoferax aquiterrae sp. nov. is proposed. The type strain is NAFc-7(T) (=
      BCRC 80210(T) = LMG 26333(T) = KCTC 23314(T)).

PMID- 22368173
TI  - Algoriphagus machipongonensis sp. nov., co-isolated with a colonial
      choanoflagellate.
AB  - A Gram-negative, non-motile, non-spore-forming bacterial strain, PR1(T), was
      isolated from a mud core sample containing colonial choanoflagellates near Hog
      Island, Virginia, USA. Strain PR1(T) grew optimally at 30  degrees C and with 3 %
      (w/v) NaCl. Strain PR1(T) contained MK-7 as the major menaquinone as well as
      carotenoids but lacked pigments of the flexirubin-type. The predominant fatty
      acids were iso-C(15 : 0) (29.4 %), iso-C(17 : 1)omega9c (18.5 %) and summed
      feature 3 (C(16 : 1)omega6c and/or C(16 : 1)omega7c; 11.3 %). The major polar
      lipids detected in strain PR1(T) were phosphatidylethanolamine, an unknown
      phospholipid, an aminophospholipid, an aminolipid and two lipids of unknown
      character. The DNA G+C content was 38.7 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences revealed that strain PR1(T) fell within the cluster
      comprising the genus Algoriphagus and was most closely related to Algoriphagus
      halophilus JC 2051(T) (95.4 % sequence similarity) and Algoriphagus lutimaris S1
      3(T) (95.3 % sequence similarity). The 16S rRNA gene sequence similarity between
      strain PR1(T) and the type strains of other species of the genus Algoriphagus
      were in the range 91-95 %. Differential phenotypic properties and phylogenetic
      and genetic distinctiveness of strain PR1(T) demonstrated that this strain was
      distinct from other members of the genus Algoriphagus, including its closest
      relative, A. halophilus. Based on phenotypic, chemotaxonomic, phylogenetic and
      genomic data, strain PR1(T) should be placed in the genus Algoriphagus as a
      representative of a novel species, for which the name Algoriphagus
      machipongonensis sp. nov. is proposed. The type strain is PR1(T) (= ATCC BAA
      2233(T) = DSM 24695(T)).

PMID- 22368174
TI  - Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin
      resistant offspring of parents with type 2 diabetes.
AB  - Recent studies reveal a strong relationship between reduced mitochondrial content
      and insulin resistance in human skeletal muscle, although the underlying factors
      responsible for this association remain unknown. To address this question, we
      analyzed muscle biopsy samples from young, lean, insulin resistant (IR) offspring
      of parents with type 2 diabetes and control subjects by microarray analyses and
      found significant differences in expression of ~512 probe pairs. We then screened
      these genes for their potential involvement in the regulation of mitochondrial
      biogenesis using RNA interference and found that mRNA and protein expression of
      lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in the IR
      offspring and was associated with decreased mitochondrial density. Furthermore,
      we show that LPL knockdown in muscle cells decreased mitochondrial content by
      effectively decreasing fatty acid delivery and subsequent activation of
      peroxisome proliferator-activated receptor (PPAR)-delta. Taken together, these
      data suggest that decreased mitochondrial content in muscle of IR offspring may
      be due in part to reductions in LPL expression in skeletal muscle resulting in
      decreased PPAR-delta activation.

PMID- 22368175
TI  - Prevention of type 1 diabetes in the rat with an allele-specific anti-T-cell
      receptor antibody: Vbeta13 as a therapeutic target and biomarker.
AB  - In earlier studies of the Iddm14 diabetes susceptibility locus in the rat, we
      identified an allele of the T-cell receptor (TCR) beta-chain, Tcrb-V13S1A1, as a
      candidate gene. To establish its importance, we treated susceptible rats with a
      depleting anti-rat Vbeta13 monoclonal antibody and then exposed them to either
      polyinosinic:polycytidylic acid or a diabetogenic virus to induce diabetes. The
      overall frequency of diabetes in the controls was 74% (n = 50), compared with 17%
      (n = 30) in the anti-Vbeta13-treated animals, with minimal islet pathology in
      nondiabetic treated animals. T cells isolated from islets on day 5 after starting
      induction showed a greater proportion of Vbeta13(+) T cells than did peripheral
      lymph node T cells. Vbeta13 transcripts recovered from day 5 islets revealed
      focused Jbeta usage and less CDR3 diversity than did transcripts from peripheral
      Vbeta13(+) T cells. CDR3 usage was not skewed in control Vbeta16 CDR3
      transcripts. Anti-rat Vbeta13 antibody also prevented spontaneous diabetes in
      BBDP rats. The Iddm14 gene is likely to be Tcrb-V13, indicating that TCR beta
      chain usage is a determinant of susceptibility to autoimmune diabetes in rats. It
      may be possible to prevent autoimmune diabetes by targeting a limited element of
      the T-cell repertoire.

PMID- 22368176
TI  - Consistent causal effect estimation under dual misspecification and implications
      for confounder selection procedures.
AB  - In a previously published article in this journal, Vansteeland et al. [Stat
      Methods Med Res. Epub ahead of print 12 November 2010. DOI:
      10.1177/0962280210387717] address confounder selection in the context of causal
      effect estimation in observational studies. They discuss several selection
      strategies and propose a procedure whose performance is guided by the quality of
      the exposure effect estimator. The authors note that when a particular linearity
      condition is met, consistent estimation of the target parameter can be achieved
      even under dual misspecification of models for the association of confounders
      with exposure and outcome and demonstrate the performance of their procedure
      relative to other estimators when this condition holds. Our earlier published
      work on collaborative targeted minimum loss based learning provides a general
      theoretical framework for effective confounder selection that explains the
      findings of Vansteelandt et al. and underscores the appropriateness of their
      suggestions that a confounder selection procedure should be concerned with
      directly targeting the quality of the estimate and that desirable estimators
      produce valid confidence intervals and are robust to dual misspecification. 

PMID- 22368177
TI  - A semi-parametric approach to the frequency of occurrence under a simple
      crossover trial.
AB  - To analyze the frequency of occurrence for an event of interest in a crossover
      design, we propose a semi-parametric approach. We develop two point estimators
      and four interval estimators in closed forms for the treatment effect under a
      random effects multiplicative risk model. Using Monte Carlo simulations, we
      evaluate these estimators and compare the four interval estimators with the
      classical interval estimator suggested elsewhere in a variety of situations. We
      note that the point estimator using the ratio of two arithmetic averages of mean
      frequencies under a multiplicative risk model can be comparable to the point
      estimator using the ratio of two geometric averages of mean frequencies. We note
      that as long as the number of patients per group is large, all the four interval
      estimators developed here can perform well. We also note that the classical
      interval estimator derived under the commonly assumed Poisson distribution for
      the frequency data can be conservative and lose precision if the Poisson
      distribution assumption is violated. We use a double-blind randomized crossover
      trial comparing salmeterol with a placebo in exacerbations of asthma to
      illustrate the practical use of these estimators. 

PMID- 22368178
TI  - The channel capacity of a diagnostic test as a function of test sensitivity and
      test specificity.
AB  - We apply the information theory concept of "channel capacity" to diagnostic test
      performance and derive an expression for channel capacity in terms of test
      sensitivity and test specificity. The expected value of the amount of information
      a diagnostic test will provide is equal to the "mutual information" between the
      test result and the disease state. For the case in which only two test results
      and two disease states are considered, mutual information, I(D;R), is a function
      of sensitivity, specificity, and the pretest probability of disease. The channel
      capacity of the test is the maximal value of I(D;R) for a given sensitivity and
      specificity. After deriving an expression for I(D;R) in terms of sensitivity,
      specificity, and pretest probability, we solve for the value of pretest
      probability that maximizes I(D;R). Channel capacity is obtained by using this
      value of pretest probability to calculate I(D;R). Channel capacity provides a
      convenient and meaningful single parameter measure of diagnostic test
      performance. It quantifies the upper limit of the amount of information a
      diagnostic test can be expected to provide about a patient's disease state. 

PMID- 22368179
TI  - Organochlorine pesticide residues in biological compartments of healthy mothers.
AB  - The present study was conducted to detect placental and breast milk (BM) transfer
      of organochlorine pesticides (OCPs) between biological compartments in healthy
      lactating mothers. The study explores the effect of parity, breast-feeding and
      urban/rural residence on body burden of OCP residues. The study included 38
      healthy participants submitted to cesarean delivery. Sociodemographic data and
      specimens of maternal and umbilical sera, adipose tissue (Adp T) and BM were
      collected. Specimens were analyzed to detect OCP residues. The lindane in BM,
      o,p'-dichlorodiphenyldichloroethane (DDD) in maternal serum (MS) and total
      dichlorodiphenyltrichloroethane (DDT) and o,p'-dichlorodiphenyldichloroethylene
      in umbilical serum were the only detected residues in significantly higher
      frequencies and/or means in the primigravidae than multigravidae. There was a
      high risk of detecting o,p'-DDD (odds ratio = 8.3) in umbilical serum of the
      mothers with o,p'-DDD detected in the MS. Total DDT was detected in about 65% of
      specimens of BM, MS and Adp T and in about 40% of the umbilical serum specimens.
      There was only a significant positive correlation between total DDT residues in
      the BM and Adp T. Total DDT residues in umbilical serum and Adp T were
      significantly higher in the urban than in the rural mothers. The detection of
      some OCPs in maternal biological compartments suggests their potential placental
      and BM transfer to her child during pregnancy and lactation, respectively.
      Furthermore, it might reflect the persistence or recent use of these pesticides
      in the environment.

PMID- 22368180
TI  - Characterization of species-specific repeats in 613 prokaryotic species.
AB  - Prokaryotes are in general believed to possess small, compactly organized
      genomes, with repetitive sequences forming only a small part of them.
      Nonetheless, many prokaryotic genomes in fact contain species-specific repeats
      (>85 bp long genomic sequences with less than 60% identity to other species) as
      we have previously demonstrated. However, it is not known at present how frequent
      such species-specific repeats are and what their functional roles in bacterial
      genomes may be. Therefore, we have conducted a comprehensive survey of
      prokaryotic species-specific repeats and characterized them to examine as to
      whether there are functional classes among different repeats or not and how they
      are mutually related to each other. Of the 613 distinct prokaryotic species
      analyzed, 97% were found to contain at least one species-specific repeats. It
      seems interesting to note that the species-specific repeats thus identified
      appear to be functionally variable in different genomes: in some genomes, they
      are mostly associated with duplicated protein-coding genes, whereas in some other
      genomes with rRNA and tRNA genes. Contrary to what may be expected, only one
      fourth of the species-specific repeats were found to be associated with mobile
      genetic elements.

PMID- 22368181
TI  - Alternative splicing regulates targeting of malate dehydrogenase in Yarrowia
      lipolytica.
AB  - Alternative pre-mRNA splicing is a major mechanism contributing to the proteome
      complexity of most eukaryotes, especially mammals. In less complex organisms,
      such as yeasts, the numbers of genes that contain introns are low and cases of
      alternative splicing (AS) with functional implications are rare. We report the
      first case of AS with functional consequences in the yeast Yarrowia lipolytica.
      The splicing pattern was found to govern the cellular localization of malate
      dehydrogenase, an enzyme of the central carbon metabolism. This ubiquitous enzyme
      is involved in the tricarboxylic acid cycle in mitochondria and in the glyoxylate
      cycle, which takes place in peroxisomes and the cytosol. In Saccharomyces
      cerevisiae, three genes encode three compartment-specific enzymes. In contrast,
      only two genes exist in Y. lipolytica. One gene (YlMDH1, YALI0D16753g) encodes a
      predicted mitochondrial protein, whereas the second gene (YlMDH2, YALI0E14190g)
      generates the cytosolic and peroxisomal forms through the alternative use of two
      3'-splice sites in the second intron. Both splicing variants were detected in
      cDNA libraries obtained from cells grown under different conditions. Mutants
      expressing the individual YlMdh2p isoforms tagged with fluorescent proteins
      confirmed that they localized to either the cytosolic or the peroxisomal
      compartment.

PMID- 22368182
TI  - Insight into the molecular evolution of non-specific lipid transfer proteins via
      comparative analysis between rice and sorghum.
AB  - Phylogenetic analysis was conducted on 9 kDa non-specific lipid transfer protein
      (nsLTP) genes from nine plant species. Each of the five classified types in
      angiosperms exhibited eight conserved cysteine patterns. The most abundant nsLTP
      genes fell into the type I category, which was particularly enriched in a grass
      specific lineage of clade I.1. Six pairs of tandem copies of nsLTP genes on the
      distal region of rice chromosomes 11 and 12 were well-preserved under concerted
      evolution, which was not observed in sorghum. The transgenic promoter-reporter
      assay revealed that both rice and sorghum nsLTP genes of type I displayed a
      relatively conserved expression feature in the epidermis of growing tissue,
      supporting its functional roles in cutin synthesis or defence against
      phytopathogens. For type I, the frequent expression in the stigma and seed are
      indicative of functional involvement in pistil-pollen interactions and seed
      development. By way of contrast, several type V genes were observed, mainly in
      the vascular bundle of the rosette as well as the young shoots, which might be
      related with vascular tissue differentiation or defence signalling. Compared with
      sorghum, the highly redundant tissue-specific expression pattern among members of
      rice nsLTP genes in clade I.1 suggests that concerted evolution via gene
      conversion favours the preservation of crucial expression motifs via the
      homogenization of proximal promoter sequences under high selection constraints.
      However, extensive regulatory subfunctionalization might also have occurred under
      relative low selection constraints, resulting in functional divergence at the
      expression level.

PMID- 22368183
TI  - Growth hormone doping in sports: a critical review of use and detection
      strategies.
AB  - GH is believed to be widely employed in sports as a performance-enhancing
      substance. Its use in athletic competition is banned by the World Anti-Doping
      Agency, and athletes are required to submit to testing for GH exposure. Detection
      of GH doping is challenging for several reasons including identity/similarity of
      exogenous to endogenous GH, short half-life, complex and fluctuating secretory
      dynamics of GH, and a very low urinary excretion rate. The detection test
      currently in use (GH isoform test) exploits the difference between recombinant GH
      (pure 22K-GH) and the heterogeneous nature of endogenous GH (several isoforms).
      Its main limitation is the short window of opportunity for detection (~12-24 h
      after the last GH dose). A second test to be implemented soon (the biomarker
      test) is based on stimulation of IGF-I and collagen III synthesis by GH. It has a
      longer window of opportunity (1-2 wk) but is less specific and presents a variety
      of technical challenges. GH doping in a larger sense also includes doping with GH
      secretagogues and IGF-I and its analogs. The scientific evidence for the
      ergogenicity of GH is weak, a fact that is not widely appreciated in athletic
      circles or by the general public. Also insufficiently appreciated is the risk of
      serious health consequences associated with high-dose, prolonged GH use. This
      review discusses the GH biology relevant to GH doping; the virtues and
      limitations of detection tests in blood, urine, and saliva; secretagogue
      efficacy; IGF-I doping; and information about the effectiveness of GH as a
      performance-enhancing agent.

PMID- 22368184
TI  - The hazards of interrupting anticoagulation therapy in atrial fibrillation.

PMID- 22368185
TI  - Scar extent, left ventricular end-diastolic volume, and wall motion abnormalities
      identify high-risk patients with previous myocardial infarction: a
      multiparametric approach for prognostic stratification.
AB  - AIMS: We sought to investigate whether combining left ventricular (LV) volumes,
      regional wall motion abnormalities, and scar tissue extent obtained by cardiac
      magnetic resonance (CMR) improves risk stratification of patients with previous
      myocardial infarction (MI). METHODS AND RESULTS: In 231 consecutive patients (age
      64 +/- 11 years, males 89%) with previous MI, we quantified LV volumes and
      regional wall motion abnormalities by cine CMR, and measured the extent of the
      infarction scar by late gadolinium enhancement (LGE). During follow-up (median,
      3.2 years) cardiac events (cardiac death or appropriate intra-cardiac
      defibrillator shocks) occurred in 19 patients. After adjustment for age, an
      extent of LGE >12.7%, an LV end-diastolic volume >105 mL/m(2), and a wall motion
      score index >1.7 were independent associated with adverse cardiac events at
      multivariate analysis (P < 0.05, P < 0.001, and P < 0.01, respectively). The
      patients with none of these factors, and those with one or two factors, showed a
      lower risk of cardiac events [hazard ratio (HR) = 0.112, P < 0.01 and HR = 0.261,
      P < 0.05] than those with three factors. The cumulative event-rate estimated at 4
      years was 29.6% in patients with all three factors, 7.7% in those with one or two
      factors, and 3.5% in patients with none of these factors. CONCLUSION: A
      multiparametric CMR approach, which includes the measure of scar tissue extent,
      LV end-diastolic volume and regional wall motion abnormalities, improves risk
      stratification of patients with previous MI.

PMID- 22368186
TI  - Essential messages from the ESC/EACTS guidelines on myocardial revascularization.

PMID- 22368187
TI  - Diffusing capacity predicts long-term survival after lung resection for cancer.
AB  - OBJECTIVES: Predictors of long-term survival for patients with lung cancer assist
      in individualizing treatment recommendations. Diffusing capacity (DLCO) is a
      predictor of complications after resection for lung cancer. We sought to
      determine whether DLCO is also prognostic for long-term survival after lung
      resection for cancer. METHODS: We assessed survival among patients in our
      prospective database who underwent lung resection for cancer between 1980-2006.
      Potential prognostic factors for all-cause mortality were evaluated by computing
      average annual hazard rates, and variables significantly associated with survival
      were included in multivariable Cox modelling. Multiple imputation was used to
      address missing values. RESULTS: Among 854 unique patients, there were 587
      deaths. The median follow-up time from surgery was 9.6 years. Predictors of
      survival included age, stage, performance status, body mass index, history of
      myocardial infarction, renal function and DLCO. On univariate analysis, the
      hazard ratio increased incrementally compared with those with a DLCO of >= 80%
      (70-79%, 1.12; 60-69%, 1.29; <60%, 1.35). On multivariable analysis, DLCO was an
      independent predictor of long-term survival for all patients (corrected for all
      other important covariates; HR 1.04 per 10-point decrement; 95% CI 1.00-1.08; P =
      0.05). Its prognostic ability for long-term survival was above and beyond its
      influence on operative mortality. CONCLUSIONS: DLCO is an independent and
      clinically important determinant of long-term survival after major lung resection
      for cancer, a finding that is not generally known. Knowledge of this may help
      improve selection of patients for lung resection and may help tailor the extent
      of resection, when possible, in order to appropriately balance operative risk
      with long-term outcomes.

PMID- 22368188
TI  - Postoperative neurodevelopmental outcome of patients with hypoplastic left heart
      complex: hybrid versus Norwood strategy.

PMID- 22368189
TI  - Robotic extended thymectomy for early-stage thymomas.
AB  - OBJECTIVES: The aim of this study was to report a single referral centre
      experience in robotic extended thymectomy for clinical early-stage thymomas,
      evaluating its safety, feasibility and efficacy, with special regard to
      oncological outcomes. METHODS: Between April 2002 and February 2011, we
      retrospectively selected all those patients who underwent robotic thymectomy for
      clinical early-stage thymomas. Operative time, morbidity, mortality, duration of
      hospitalization and overall and disease-free survival were analysed. RESULTS:
      There were 14 patients (8 males, 6 females) with a mean age of 65.2 years (range
      23-81). One patient suffered from myasthenia gravis. The WHO classifications
      were: A in two cases, AB in four cases, B1 in three cases, B2 in two cases and B3
      in three cases. The Masaoka stages were: I in seven cases, IIA in four cases, IIB
      in two cases and III in one case. The mean operative time was 139 min. No intra
      operative complication or death occurred. Conversion to open surgery was required
      in two cases. Minor complications occurred in two patients (14.2%) due to pleural
      effusion. The mean hospitalization was 4.0 days. Five patients underwent adjuvant
      radiotherapy. All patients were alive with no disease recurrence, with a median
      follow-up of 14.5 months (range 1-98). CONCLUSIONS: Robotic thymectomy is a safe
      and feasible technique, with a short operative time and low morbidity. Even on a
      small series with short follow-up, robotic extended thymectomy for thymoma
      appeared to be an effective treatment for early-stage thymomas.

PMID- 22368190
TI  - Bidirectional cavopulmonary shunt with additional pulmonary blood flow: a failed
      or successful strategy?
AB  - OBJECTIVES: In patients with single ventricle physiology, Fontan circulation is
      considered as the optimal surgical approach, although it entails a growing
      incidence of late complications. It has been speculated that the association of
      bidirectional cavopulmonary shunt (BCPS) and additional pulmonary blood flow
      (APBF) might provide long-lasting palliation. The present study was undertaken to
      assess the long-term outcome of this strategy. METHODS: A group of 70 patients
      with single ventricle physiology, who underwent BCPS with APBF between 1990 and
      2000, were reviewed retrospectively. Median age at operation was 2 years (range:
      0.1-27 years). Unilateral BCPS was performed in 60 patients (86%), bilateral BCPS
      in 9 and the Kawashima procedure in 1. APBF was provided through antegrade
      pulmonary outflow tract in 43 patients (61%) and by aortopulmonary shunt in 27
      (39%). Two patients died early and three were lost to follow-up. Mean follow-up
      of the 65 remaining patients was 13.5 +/- 4 years. End-points were death, need
      for heart transplantation (HTx) or Fontan completion and functional outcome.
      RESULTS: Five patients died (two after HTx, three from ventricular failure);
      overall actuarial survival was 89 +/- 4% at 15 years. Six patients underwent HTx
      (one after Fontan completion) with two early deaths and no late mortality. Fifty
      one patients underwent Fontan completion (11 with additional palliative
      procedures before completion); there was no early or late mortality following
      Fontan completion; one patient underwent HTx. Among the remaining six patients
      with BCPS and APBF, two were not suitable for Fontan completion and four remained
      suitable. Overall, clinical failure (mortality, HTx, unsuitability for Fontan
      completion) occurred in 13 patients (19%). Risk factors for clinical failure were
      older age at BCPS (P = 0.01) and postoperative complications after BCPS (P =
      0.001). Considering late mortality, HTx and Fontan completion as strategic
      failures, the actuarial freedom from these events was 20 +/- 5% at 10 years.
      CONCLUSIONS: BCPS with APBF approach: (i) fails as a strategy for definitive
      palliation, (ii) provides a high survival rate, (iii) does not preclude a
      successful Fontan completion and (iv) may delay the long-term deleterious
      consequences of Fontan circulation. Palliation by BCPS with APBF should be
      achieved early in life.

PMID- 22368191
TI  - Analysis of vascular endothelial growth factor gene expression in the tissues of
      patients with chronic venous insufficiency.
AB  - OBJECTIVE: Immunohistochemical techniques have revealed the presence of vascular
      endothelial growth factor (VEGF) in the epidermis of patients with chronic venous
      disease (CVD). Our objective was to perform a quantitative analysis of the VEGF
      gene transcription in tissues that are potential sources of this factor (skin,
      varicose veins [VV] and great saphenous vein [GSV]) in patients with CVD.
      METHODS: In all, 212 skin and venous tissue samples were collected from patients
      diagnosed with CVD and controls. The VEGF gene expression was analysed using
      quantitative realtime polymerase chain reaction (PCR). RESULTS: The skin VEGF
      expression was lower in the CVD group than in the control group (P = 0.04). There
      were no significant differences between the insufficient GSV of the CVD group and
      the control healthy vein (P = 0.22). There was a greater expression of VEGF in
      the VV of the CVD group than in the control healthy vein (P = 0.03). Comparison
      of the VEGF expression between the different tissue types in the CVD group
      revealed significant differences between the skin and GSV (P = 0.02) and between
      the skin and the VV (P = 0.004), and between the VV and the GSV (P = 0.02).
      CONCLUSIONS: The results of the present study show an over-expression of VEGF
      gene in the VV tissue of patients with CVD. Based on the data in patients with C2
      disease, the VVs appear to be the source of increased VEGF expression.

PMID- 22368192
TI  - Curative resection and reconstruction of the inferior vena cava after extensive
      infiltration with low-grade endometrial stromal sarcoma.
AB  - Endometrial stromal sarcoma (ESS) rarely infiltrates the great vessels. We report
      a successful surgical resection of the inferior vena cava (IVC) after extensive
      infiltration with metastatic low-grade ESS. A case of presumed recurrence of low
      grade ESS demonstrated complete IVC occlusion from tumour thrombus with extensive
      local disease. Radical resection of the tumour and caval reconstruction was
      performed. The IVC graft was thrombosed at short-term follow-up. Curative
      resection of extensive caval infiltration with metastatic low-grade ESS can be
      achieved. Caval reconstructive procedures may be redundant in the presence of an
      adequate collateral circulation.

PMID- 22368193
TI  - Middle cerebral air embolism after foam sclerotherapy.
AB  - In the recent past, eight cases of transient ischaemic attack or cerebral
      vascular accident related to foam sclerotherapy have been reported. The following
      case is reported to add to the world clinical experience and raises the concern
      that foam sclerotherapy should continue to be evaluated and reported rigorously
      to establish the incidence of potentially devastating complications. While
      waiting for clinical studies to further establish best practice in this area of
      treatment, it may be in our patients' best interests to reserve the option of
      foaming sclerosants for selected rather than routine cases of venous
      insufficiency.

PMID- 22368194
TI  - Multimodality imaging of left ventricular aneurysm: tools of the trade.

PMID- 22368195
TI  - Impact of type 2 diabetes on serial changes in tissue characteristics of coronary
      plaques: an integrated backscatter intravascular ultrasound analysis.
AB  - AIMS: Several studies have demonstrated that type 2 diabetes mellitus (T2DM) is
      associated with accelerated atherosclerosis, which results in an increased risk
      of coronary vascular events. However, serial changes in plaque characteristics
      have not been reported in vivo. We evaluated the progression of coronary
      atherosclerosis in patients with T2DM using an integrated backscatter
      intravascular ultrasound (IB-IVUS) examination. METHODS AND RESULTS: Forty-two
      T2DM and 48 non-diabetic patients who underwent percutaneous coronary
      intervention were enrolled in the study. Non-culprit 20-mm length coronary
      lesions with mild-to-moderate stenosis were measured using a 40-MHz (motorized
      pullback of 0.5 mm/s) IVUS catheter. IVUS examinations were performed on one
      target lesion in each patient. Six months later, a follow-up IVUS examination was
      repeated in the same coronary segment imaged at the baseline examination. T2DM
      patients demonstrated a greater total plaque volume (TPV; 139 +/- 53 vs. 114 +/-
      45 mm(3), P = 0.02) and total lipid volume (TLV; 67 +/- 26 vs. 55 +/- 30 mm(3), P
      = 0.039) at the baseline examination. The progression of TPV (8.6 +/- 15.4 vs. 
      2.2 +/- 16.0%, P < 0.01) and TLV (10.8 +/- 28.8 vs. -2.5 +/- 20.0%, P < 0.05)
      from the baseline was observed in T2DM patients, but not in non-diabetic
      patients. The increase in TLV was blunted in T2DM patients who achieved HbA1c
      levels of <6.5%. CONCLUSION: Accelerated plaque progression with an increase in
      the lipid-rich component of non-culprit plaques was observed in T2DM, despite the
      use of standard medical treatment. Better glycaemic control ameliorated the
      worsening of plaque characteristics in T2DM.

PMID- 22368196
TI  - TB testing by tender 'will never be welcomed'.

PMID- 22368198
TI  - Website highlights the welfare impact of inherited problems in pets.

PMID- 22368199
TI  - SBV confirmed in Cornwall.

PMID- 22368203
TI  - Giving dogs the best start in life.

PMID- 22368204
TI  - New rules for puppy registrations.

PMID- 22368209
TI  - Conservation: clarifying the risk from herpesvirus to captive Asian elephants.

PMID- 22368210
TI  - Humanitarian crises, livelihoods and veterinary interventions.

PMID- 22368211
TI  - Antimicrobial selective pressure in pet-owning healthcare workers.

PMID- 22368212
TI  - Prevention of Schmallenberg virus.

PMID- 22368213
TI  - Government vets' involvement in veterinary education.

PMID- 22368214
TI  - Oxytocin selectively increases perceptions of harm for victims but not the desire
      to punish offenders of criminal offenses.
AB  - The neuropeptide oxytocin functions as a hormone and neurotransmitter and
      facilitates complex social cognition and approach behavior. Given that empathy is
      an essential ingredient for third-party decision-making in institutions of
      justice, we investigated whether exogenous oxytocin modulates empathy of an
      unaffected third-party toward offenders and victims of criminal offenses. Healthy
      male participants received intranasal oxytocin or placebo in a randomized, double
      blind, placebo-controlled, between-subjects design. Participants were given a set
      of legal vignettes that described an event during which an offender engaged in
      criminal offenses against victims. As an unaffected third-party, participants
      were asked to rate those criminal offenses on the degree to which the offender
      deserved punishment and how much harm was inflicted on the victim. Exogenous
      oxytocin selectively increased third-party decision-makers' perceptions of harm
      for victims but not the desire to punish offenders of criminal offenses. We argue
      that oxytocin promoted empathic concern for the victim, which in turn increased
      the tendency for prosocial approach behavior regarding the interpersonal
      relationship between an unaffected third-party and a fictional victim in the
      criminal scenarios. Future research should explore the context- and person
      dependent nature of exogenous oxytocin in individuals with antisocial personality
      disorder and psychopathy, in whom deficits in empathy feature prominently.

PMID- 22368216
TI  - Differences in occupational, transportation, domestic, and leisure-time physical
      activities: do geographical location and socio-cultural status matter?
AB  - BACKGROUND: Researchers have recently expressed their concern for the health of
      Francophones and rural dwellers in Canada. Their levels of physical activity may
      explain part of the observed differences. However, little is known about the
      physical activity levels of these 2 groups. The purpose of this study was to
      assess levels of physical activity among a sample of Francophones and rural
      dwellers. The study also assessed the associations of various types of physical
      activity to measures of health status. METHODS: A quota-based convenience sample
      of 256 adults from Northern Ontario was surveyed using the IPAQ and the SF-12.
      RESULTS: There were no significant differences in activity levels between
      language groups (P = .06) or geographical groups (P = .22) on the combined
      dependent variables based on MANOVA. Leisure-time physical activity scores were
      consistently associated to better physical component summary scores of the SF-12.
      CONCLUSIONS: Implications for practice include that leisure-time physical
      activities have been at the forefront of public health promotion, and our
      findings support this approach. Further, population specific interventions are
      indeed important, however, within this Canadian context when identifying target
      groups one must look beyond sociocultural status or geographical location.

PMID- 22368217
TI  - Prevalence of New Zealand children and adolescents achieving current physical
      activity and television watching recommendations.
AB  - BACKGROUND: Aims were to investigate sex, ethnicity, and age differences in
      achieving daily step count and television (TV) watching recommendations in
      schoolchildren. METHODS: Participants were 615 children (n = 325) and adolescents
      (n = 290) aged 5 to 16 years. Activity was assessed over 5 days using pedometers;
      TV time was collected via parental proxy-report and self-report. Ethnic, sex, and
      age differences in step counts, TV time, and odds of meeting TV and step count
      recommendations were examined for weekdays, weekend days, and overall using
      generalized estimation equation modeling. RESULTS: Overall, girls were more
      active than boys (P < .001). Adolescents were more active than children (P =
      .044), watched more TV (P = .005), and were less likely to meet TV watching
      recommendations (P = .004). Non-European children watched significantly more TV
      (P = .008), and were significantly less likely to meet TV recommendations than
      non-European children (P = .001). Participants watched more TV and accumulated
      less steps on weekend days than weekdays. CONCLUSIONS: Multifaceted interventions
      focusing on both increasing activity and decreasing TV time are needed,
      especially on weekends. Children and girls may benefit more from activity
      interventions, while ethnic-specific interventions focusing on TV habits may be
      most efficacious for adolescents.

PMID- 22368218
TI  - The association of trail use with weather-related factors on an urban greenway.
AB  - PURPOSE: To study the association between weather-related measures and
      objectively measured trail use across 3 seasons. BACKGROUND: Weather has been
      reported as a barrier to outdoor physical activity (PA), but previous studies
      have explained only a small amount of the variance in PA using weather-related
      measures. METHODS: The dependent variable of this study was trail use measured as
      mean hourly trail counts by an infrared trail counter located on a greenway. Each
      trail count represents 1 person breaking the infrared beam of the trail counter.
      Two sources of weather-related measures were obtained by a site-specific weather
      station and a public domain weather source. RESULTS: Temperature, relative
      humidity, and precipitation were significantly correlated with trail counts
      recorded during daylight hours. More precise hourly weather-related measures
      explained 42% of the variance in trail counts, regardless of the weather data
      source with temperature alone explaining 18% of the variance in trail counts.
      After controlling for all seasonal and weekly factors, every 1 degrees F increase
      in temperature was associated with an increase of 1.1 trail counts/hr up to 76
      degrees F, at which point trail use began to slightly decrease. CONCLUSION:
      Weather-related factors have a moderate association with trail use along an urban
      greenway.

PMID- 22368220
TI  - Interaction of perceived neighborhood walkability and self-efficacy on physical
      activity.
AB  - OBJECTIVES: Few social ecological studies have considered the joint effects of
      intrapersonal and environmental influences on physical activity. This study
      investigated the interaction of self-efficacy and perceived neighborhood
      walkability in predicting neighborhood-based physical activity and how this
      relationship varied by gender and body mass index. METHODS: Data were derived
      from a cross-sectional investigation of environmental and psychosocial correlates
      of physical activity among adults (n = 585). Participants completed a detailed 7
      day physical activity log booklet, along with a questionnaire that included
      measures of neighborhood walkability, self-efficacy, and several sociodemographic
      items. Factorial analysis of variance tests were used to examine the main effects
      of and interaction between walkability and self-efficacy. RESULTS: In predicting
      neighborhood-based physical activity, significant interactions were observed
      between self-efficacy and neighborhood walkability for females (but not for
      males) and for overweight/obese participants (but not for healthy weight
      individuals). Women and overweight/obese individuals with low self-efficacy
      demonstrated substantially greater physical activity when living in a high
      walkable neighborhood. CONCLUSIONS: Physical activity research and promotion
      efforts should take into account both environmental and personal factors and the
      interrelationships between them that influence active living.

PMID- 22368219
TI  - Injuries in sedentary individuals enrolled in a 12-month, randomized, controlled,
      exercise trial.
AB  - BACKGROUND: The risk of musculoskeletal injury with the introduction of moderate
      to-vigorous exercise in sedentary adults is not well established. The purpose of
      this report is to examine the effect of a 12-month exercise intervention on
      musculoskeletal injury and bodily pain in predominately overweight, sedentary men
      (n = 102) and women (n = 100), ages 40 to 75 years. METHODS: Participants were
      randomized to a moderate-to-vigorous aerobic exercise intervention (EX) (6 d/wk,
      60 min/d, 60% to 85% max. heart rate) or usual lifestyle control (CON).
      Participants completed a self-report of musculoskeletal injury and body pain at
      baseline and 12-months. RESULTS: The number of individuals reporting an injury
      (CON; 28% vs. EX; 28%, P = .95) did not differ by group. The most commonly
      injured site was lower leg/ankle/foot. The most common causes of injury were
      sports/physical activity, home maintenance, or "other." In the control group,
      bodily pain increased over the 12 months compared with the exercise group (CON 
      7.9, EX -1.4, P = .05). Baseline demographics and volume of exercise were not
      associated with injury risk. CONCLUSIONS: Previously sedentary men and women
      randomized to a 12-month aerobic exercise intervention with a goal of 360 min/wk
      reported the same number of injuries as those in the control group and less
      bodily pain.

PMID- 22368221
TI  - Physical activity and intelligence: a causal exploration.
AB  - BACKGROUND: Studies involving animals and older adults suggest that physical
      activity (PA) might lead to improved cognitive ability in general, and enhanced
      intelligence scores (IQ) in particular. However, there are few studies involving
      young persons and none controlling for the possibility that those with better
      cognitive skills are more likely to engage in PA. METHODS: Data are from the
      Mater-University of Queensland Study of Pregnancy. We measured IQ at the 14-year
      follow-up and IQ and PA at 21 years. Mean IQ scores are presented at the 21-year
      follow-up adjusted for IQ at 14 years, and PA and other variables. RESULTS:
      Measures of vigorous exercise, less vigorous exercise, walking, and vigorous
      activity apart from exercise, produced inconsistent results. Increased levels of
      less vigorous exercise were associated with higher IQ, but neither higher levels
      of vigorous exercise nor walking were associated with IQ. For vigorous activity
      at work or in the home, the associations are curvilinear, with more and less
      activity both associated with lower IQ. CONCLUSIONS: While there is an
      association between some indicators of PA and IQ, there was no consistent
      evidence that higher PA levels might lead to increased IQ scores.

PMID- 22368222
TI  - Reliability and validity of CHAMPS self-reported sedentary-to-vigorous intensity
      physical activity in older adults.
AB  - BACKGROUND: Recent research highlights the potential value of differentiating
      between categories of physical activity intensities as predictors of health and
      well-being. This study sought to assess reliability and concurrent validity of
      sedentary (ie, 1 METs), low-light (ie, >1 and <=2 METs; eg, playing cards), high
      light (ie, >2 and <3 METs; eg, light walking), moderate-to-vigorous physical
      activity (MVPA, >=3 METs), and "total activity" (>=2 METs) from the CHAMPS
      survey. Further, this study explored over-reporting and double-reporting.
      METHODS: CHAMPS data were gathered from the Seniors Neighborhood Quality of Life
      Study, an observational study of adults aged 65+ years conducted in 2 US regions.
      RESULTS: Participants (N = 870) were 75.3 +/- 6.8 years old, with 56% women and
      71% white. The CHAMPS sedentary, low-light, high-light, total activity, and MVPA
      variables had acceptable test-retest reliability (ICCs 0.56-0.70). The CHAMPS
      high-light (rho = 0.27), total activity (rho = 0.34), and MVPA (rho = 0.37)
      duration scales were moderately associated with accelerometry minutes of
      corresponding intensity, and the sedentary scale (rho = 0.12) had a lower, but
      significant correlation. Results suggested that several CHAMPS items may be
      susceptible to over-reporting (eg, walking, housework). CONCLUSIONS: CHAMPS items
      effectively measured high-light, total activity, and MVPA in seniors, but further
      refinement is needed for sedentary and low-light activity.

PMID- 22368223
TI  - Comparing the validity of 2 physical activity questionnaire formats in African
      American and Hispanic women.
AB  - BACKGROUND: The purpose of this study was to compare the validity of 2 physical
      activity questionnaire formats--one that lists activities (Checklist
      questionnaire) and one that assesses overall activities (Global questionnaire) by
      domain. METHODS: Two questionnaire formats were validated among 260 African
      American and Hispanic women (age 40-70) using 3 validation standards: 1)
      accelerometers to validate activities of ambulation; 2) diaries to validate
      physical activity domains (occupation, household, exercise, yard, family,
      volunteer/church work, and transportation); and 3) doubly-labeled water to
      validate physical activity energy expenditure (DLW-PAEE). RESULTS: The proportion
      of total variance explained by the Checklist questionnaire was 38.4% with
      diaries, 9.0% with accelerometers, and 6.4% with DLW-PAEE. The Global
      questionnaire explained 17.6% of the total variance with diaries and about 5%
      with both accelerometers and with DLWPAEE. Overall, associations with the 3
      validation standards were slightly better with the Checklist questionnaire.
      However, agreement with DLW-PAEE was poor with both formats and the Checklist
      format resulted in greater overestimation. Validity results also indicated the
      Checklist format was better suited to recall household, family, and
      transportation activities. CONCLUSIONS: Overall, the Checklist format had
      slightly better measurement properties than the Global format. Both questionnaire
      formats are better suited to rank individuals.

PMID- 22368224
TI  - Predictive validity of health-related fitness tests on back pain and related
      disability: a 6-year follow-up study among high-functioning older adults.
AB  - BACKGROUND: Back pain and related disability seem to be increasing among older
      adults. Health-related fitness tests have been developed to identify individuals
      at risk for mobility difficulties. However, poor fitness as a risk factor for
      back problems has seldom been studied. The purpose of the current study was to
      investigate whether performance in fitness tests predicts back pain and related
      disability during 6 years of follow-up. METHODS: Study population consisted of
      community-dwelling men and women, born 1927 to 1941, who participated in
      assessment of health-related fitness and reported no long-term back pain or
      related disability at baseline (n = 517). The assessment included measurements of
      body mass index (BMI), one-leg stand, backward tandem walk, trunk side-bending,
      dynamic back extension, forward squat, 6.1-m walking speed and 1-km walk time.
      RESULTS: Prospective analyses indicated that poor fitness (poorest-third) in one
      leg stand and trunk side-bending tests were the most powerful predictors of back
      pain. Regarding disability, poor fitness in dynamic back extension and overweight
      in terms of BMI >= 27 increased the risk. CONCLUSIONS: Tests of balance, trunk
      flexibility and trunk muscle endurance, as well as BMI can be implemented as
      screening tools for identifying persons with increased risk of back pain and
      related disability.

PMID- 22368225
TI  - Active living in the trucking sector: environmental barriers and health promotion
      strategies.
AB  - BACKGROUND: As one of the most underserved segments of the U.S. labor force,
      truck drivers have been associated with a series of morbid conditions intimately
      linked to their occupational milieux, their mostly unhealthful nutritional intake
      and sedentary lifestyles, and their resulting excess weight-gain. METHODS: This
      paper reports data from a baseline assessment of 25 trucking work settings
      located around interstate highways I-40 and I-85 in North Carolina. It examines
      how the environmental attributes of these work settings influence the physical
      and recreational activity behaviors of truckers, compares findings with those
      from other occupational environments, and brings to the fore a new health
      promotion paradigm for trucking worksites. RESULTS: Findings support growing
      empirical and anecdotal evidence that trucking work settings remain not only
      active-living deserts, but overall unhealthful places. A scan of physical,
      social, and information environments within trucking worksites as well as
      physical environments of surrounding communities reveal only meager opportunities
      for physical and recreational activity for truckers. CONCLUSION: This paper
      places the highly underserved population of truckers firmly within the discourse
      of worksite health promotion, and calls for comprehensive multistakeholder
      wellness strategies that address a multitude of risk factors linked to the
      occupational context.

PMID- 22368226
TI  - Correlates of sitting time in working age Australian women: who should be
      targeted with interventions to decrease sitting time?
AB  - BACKGROUND: While there is emerging evidence that sedentary behavior is
      negatively associated with health risk, research on the correlates of sitting
      time in adults is scarce. METHODS: Self-report data from 7724 women born between
      1973-1978 and 8198 women born between 1946-1951 were collected as part of the
      Australian Longitudinal Study on Women's Health. Linear regression models were
      computed to examine whether demographic, family and caring duties, time use,
      health, and health behavior variables were associated with weekday sitting time.
      RESULTS: Mean sitting time (SD) was 6.60 (3.32) hours/day for the 1973-1978
      cohort and 5.70 (3.04) hours/day for the 1946-1951 cohort. Indicators of
      socioeconomic advantage, such as full-time work and skilled occupations in both
      cohorts and university education in the mid-age cohort, were associated with high
      sitting time. A cluster of 'healthy behaviors' was associated with lower sitting
      time in the mid-aged women (moderate/high physical activity levels, nonsmoking,
      nondrinking). For both cohorts, sitting time was highest in women in full-time
      work, in skilled occupations, and in those who spent the most time in passive
      leisure. CONCLUSIONS: The results suggest that, in young and mid-aged women,
      interventions for reducing sitting time should focus on both occupational and
      leisure-time sitting.

PMID- 22368227
TI  - Cardiovascular fitness moderates the relations between estimates of obesity and
      physical self-perceptions in rural elementary school students.
AB  - BACKGROUND: Levels of physical activity decline throughout childhood. Children's
      physical self-perceptions have been found to relate to their physical activity.
      Understanding the relationships among physical self-perceptions, obesity, and
      physical activity could have important implications for interventions in
      children. METHODS: The current study investigated the moderating effect of
      cardiovascular fitness (CVF, heart rate recovery from a 3-minute step test) on
      the relationship between obesity (BMI, waist circumference) and physical self
      perceptions (athletic competence, physical appearance) in 104 fourth- and fifth
      grade children from a small rural community. RESULTS: Hierarchical regression
      analyses indicated that CVF moderated the relations between BMI and waist
      circumference on athletic competence. For children with lower fitness, higher
      waist circumference was associated with lower athletic competence, while for
      children with higher fitness levels, higher BMI was associated with higher
      athletic competence. Results also indicated that both BMI and waist circumference
      were negatively related to physical appearance. CVF moderated these relations
      such that only children with lower fitness, greater BMI and waist circumference
      was associated with poorer physical appearance scores. CONCLUSIONS: Implications
      include the need for support of fitness programs to promote psychological well
      being and to investigate the relationship between obesity and physical self
      perceptions within the context of fitness.

PMID- 22368228
TI  - Validation and reliability of the New Lifestyles NL-1000 accelerometer in New
      Zealand preschoolers.
AB  - BACKGROUND: Objective measures, such as accelerometers, are increasingly being
      used to measure physical activity (PA) levels in children, and the use of
      validated and reliable instruments is desirable when measuring the effectiveness
      of programs. The purpose of this study was to determine the validity and
      reliability of the New Lifestyles NL-1000 accelerometer among preschoolers using
      a modified version of the Children's Activity Rating Scale (CARS). METHODS:
      Fourteen preschoolers wore the NL-1000 at their waist while the device measured
      activity levels [in seconds of moderate-to-vigorous physical activity (MVPA)].
      They were also videoed for approximately 12 minutes while participating in normal
      activities at an early childhood center. At approximately 2-minute intervals,
      activity level readings derived from the NL-1000 were recorded. The video footage
      was analyzed using a modified CARS technique and the CARS scores compared with
      data obtained from the accelerometer. RESULTS: Within subject reliability was
      measured using intraclass correlation coefficients (0.58 for CARS and 0.59 for NL
      1000). Furthermore, 95% of the variation in CARS could be explained by variation
      in the accelerometer counts, with 2.4% of the variation being participant
      specific. CONCLUSION: The NL-1000 is a sufficiently reliable and valid tool for
      assessing MVPA in preschoolers.

PMID- 22368229
TI  - Influence of cut-points on patterns of accelerometry-measured free-living
      physical activity in rural and urban black South African women.
AB  - BACKGROUND: We describe the effect of 2 different accelerometer cut-points on
      physical activity (PA) patterns in rural and urban black South African women.
      METHODS: Hip-mounted uni-axial accelerometers were worn for 6 to 7 days by rural
      (n = 272) and urban (n = 16) participants. Twenty-hour (4 AM to 12 AM) PA counts
      (cts) and volumes (min.day-1) were extracted: sedentary (SED, <100 cts.min-1),
      light (100-759 cts.min-1), moderate-1 (MOD1, 760-1951 cts.min-1), moderate-2 to
      vigorous (MOD2VG, >=1952 cts.min-1), and bouts >=10 min for >=760 cts.min-1
      (MOD1VGbt) and >=1952 cts.min-1 (MOD2VGbt). RESULTS: Valid data were obtained
      from 263 rural women and 16 urban women. Total counts and average counts were
      higher (+80,399 cts.day-1, +98 cts.min-1.day-1) (P < .01), SED lower (-61 min.day
      1, P = .0042), MOD1 higher (+65 min.day-1, P < .0001), and MOD1VGbt higher (+19
      min.day-1, P = .0179) in rural women compared with urban women. Estimated
      adherence (>=30 min.day-1 for 5 days.wk-1) was 1.4-fold higher in rural women
      than urban women for MOD-1VGbt, but 3.3-fold higher in urban women than rural
      women for MOD2VGbt. CONCLUSIONS: Rural women accumulate greater amounts of PA
      than urban women within a particular count band. Depending on which moderate PA
      cut-point was used to estimate PA public health adherence, rural women could be
      classified as less physically active than urban women.

PMID- 22368230
TI  - What are the benefits of a commercial exergaming platform for college students?
      Examining physical activity, enjoyment, and future intentions.
AB  - BACKGROUND: Traditional videogames contribute to sedentary behaviors; in
      contrast, exergaming is a relatively new concept that uses videogames to promote
      exercise during game play. Nintendo Wii Fit is a commercially popular exergaming
      platform geared toward improving fitness, however, limited empirical evidence
      related to the physical and mental benefits of the Wii Fit platform currently
      exist. Therefore, the purpose of this study was to investigate possible physical
      and motivational benefits of Nintendo Wii Fit. METHODS: A repeated measures
      design was used with 30 college-aged students to explore physical activity,
      enjoyment, and future intentions of physical activity associated with Wii Fit
      exergames. RESULTS: Data supported the efficacy of Wii Fit Basic Run to
      consistently produce moderate to vigorous physical activity across participants.
      Future intentions were higher for exergaming compared with generic exercise and
      obese individuals enjoyed exergaming more than generic physical activity.
      CONCLUSIONS: The Basic Run Wii Fit game provided opportunities for accumulating
      moderate to vigorous physical activity that provided motivational benefits to
      these participants, especially those classified as obese. Future research should
      examine the ability of Wii Fit exergames to produce physical activity and
      motivation over time.

PMID- 22368231
TI  - Fcgamma receptor type IIIA polymorphism influences treatment outcomes in patients
      with rheumatoid arthritis treated with rituximab.
AB  - OBJECTIVE: To assess the association between a single nucleotide polymorphism in
      the gene of FCGR3A and the response to treatment with rituximab (RTX) in
      rheumatoid arthritis (RA). METHODS: SMART is a randomised open trial assessing
      two strategies of re-treatment in patients responding to 1 g infusion of RTX with
      methotrexate on days 1 and 15 after failure, intolerance or contraindication to
      tumour necrosis factor (TNF) blockers. Among the 224 patients included, 111 could
      be genotyped and were included in an ancillary study of SMART. Univariate and
      multivariate analyses adjusted on disease activity score on 28 joints were
      performed to assess whether FCGR3A-158V/F polymorphism was associated with
      European League Against Rheumatism response at week 24. RESULTS: Among the 111
      patients, 90 (81%) were responders of whom 30 (27%) were good responders. V
      allele carriage was significantly associated with a higher response rate (91% of
      responders vs 70%, OR 4.6 (95% CI 1.5 to 13.6), p=0.006). These results were also
      confirmed in rheumatoid factor-positive patients (93% vs 74%, p=0.025). In
      multivariate analysis, V allele carriage was independently associated with
      response to RTX (OR 3.8 (95% CI 1.2 to 11.7), p=0.023). CONCLUSION: The 158V/F
      polymorphism of FCGR3A seems to influence the response to RTX in patients with RA
      after failure, intolerance or contraindication to TNF blockers.

PMID- 22368232
TI  - The whole Shebang: the gastrointestinal tract, Escherichia coli enterotoxins and
      secretion.
AB  - This review focuses on diarrhea caused by toxins released by enterotoxigenic
      Escherichia coli. These bacteria are known to produce toxins that have adverse
      effects on the intestinal tissue in Man and animals. E. coli is contracted
      through the ingestion of water or food contaminated by this bacterium. Generally,
      E. coli colonizes the intestinal mucosa where it multiplies and causes damage to
      the target cells or interferes with the homeostasis that prevails in the
      gastrointestinal tract. Enteropathogens such as E. coli are only able to exhibit
      their effects after colonization of the intestinal mucosa from where they release
      their toxins. These bacteria mainly affect chloride ions secretion through second
      messenger pathways resulting in secretory diarrhea. In this review, the
      association of bacteria with the gastrointestinal tract as pathogens and the
      resulting effects on the various systems of the intestine, including the nervous
      system and mediators leading to secretion and diarrhea are examined.

PMID- 22368233
TI  - Strong antiviral activity of the new l-hydroxycytidine derivative, l-Hyd4FC, in
      HBV-infected human chimeric uPA/SCID mice.
AB  - BACKGROUND: Suppression of viral replication with nucleoside/nucleotide
      inhibitors has been shown to greatly improve the outcome of chronic HBV
      infection. beta-l-nucleoside analogues, especially beta-l-deoxycytidine
      derivatives represent one of the most efficient groups of antiretroviral
      compounds. We recently described that hydroxylation of the amino group of these
      beta-l-deoxycytidine derivatives preserved their strong HBV inhibitory activity
      in vitro, but strongly reduced their cytotoxicity. From this new group of
      compounds we selected beta-l-2',3'-didehydro-2',3'-dideoxy-N(4)-hydroxy-5
      fluorocytidine (l-Hyd4FC) for a first in vivo investigation. The aim of this
      study was to determine the antiviral activity of l-Hyd4FC in HBV-infected human
      liver chimeric urokinase plasminogen activator (uPA)/SCID mice. METHODS: Stably
      infected animals (median 6*10(7) HBV DNA/ml) were injected daily with either l
      Hyd4FC (50 mg/kg) or saline as controls. Mice treated with lamivudine served to
      compare the in vivo antiviral potency of l-Hyd4FC. Virological changes were
      determined by quantitative PCR. RESULTS: Treatment with l-Hyd4FC for 4 weeks
      induced a 2-log reduction of viraemia, while a median 1.5-log decline was
      achieved with lamivudine. Intrahepatically, l-Hyd4FC induced a median eightfold
      decline of viral activity (relaxed circular DNA/covalently closed circular DNA),
      and threefold reduction of pregenomic RNA/GAPDH levels. No significant decline of
      subgenomic HBV transcripts, as well as of circulating hepatitis B e antigen and
      hepatitis B surface antigen was detected. Maintenance of human serum albumin
      concentrations throughout the study, negative TUNEL staining and occurrence of
      viral rebound after drug withdrawal indicated that l-Hyd4FC was not toxic in
      human hepatocytes. CONCLUSIONS: Administration of l-Hyd4FC in uPA/SCID mice
      harbouring HBV-infected human hepatocytes demonstrated the high antiviral potency
      of this drug in vivo. Such characteristics make l-Hyd4FC a good candidate for
      further investigations a as potential HBV therapeutic agent.

PMID- 22368234
TI  - The treatment of hallucinations in schizophrenia spectrum disorders.
AB  - This article reviews the treatment of hallucinations in schizophrenia. The first
      treatment option for hallucinations in schizophrenia is antipsychotic medication,
      which can induce a rapid decrease in severity. Only 8% of first-episode patients
      still experience mild to moderate hallucinations after continuing medication for
      1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally
      effective against hallucinations, but haloperidol may be slightly inferior. If
      the drug of first choice provides inadequate improvement, it is probably best to
      switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice
      for patients who are resistant to 2 antipsychotic agents. Blood levels should be
      above 350-450 MUg/ml for maximal effect. For relapse prevention, medication
      should be continued in the same dose. Depot medication should be considered for
      all patients because nonadherence is high. Cognitive-behavioral therapy (CBT) can
      be applied as an augmentation to antipsychotic medication. The success of CBT
      depends on the reduction of catastrophic appraisals, thereby reducing the
      concurrent anxiety and distress. CBT aims at reducing the emotional distress
      associated with auditory hallucinations and develops new coping strategies.
      Transcranial magnetic stimulation (TMS) is capable of reducing the frequency and
      severity of auditory hallucinations. Several meta-analyses found significantly
      better symptom reduction for low-frequency repetitive TMS as compared with
      placebo. Consequently, TMS currently has the status of a potentially useful
      treatment method for auditory hallucinations, but only in combination with state
      of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered
      a last resort for treatment-resistant psychosis. Although several studies showed
      clinical improvement, a specific reduction in hallucination severity has never
      been demonstrated.

PMID- 22368235
TI  - Clinical manifestations of self-disorders and the Gestalt of schizophrenia.
AB  - Anomalies of self-experience (self-disorders) constitute crucial phenotypes of
      the schizophrenia spectrum. The following qualitative study demonstrates a
      variety of these core experiential anomalies. From a sample of 36 first-admitted
      patients, all of whom underwent a comprehensive psychiatric evaluation, including
      the EASE scale (Examination of Anomalous Self-Experience), 2 schizophrenia
      patients were selected for detailed psychopathological presentation and
      discussion. The vignettes provide prototypical examples of what has been termed
      self-disorders in schizophrenia, ie, pervasive and enduring (mainly) trait
      phenomena which constitute essential aspects of the spectrum.

PMID- 22368236
TI  - Neurophysiological studies of auditory verbal hallucinations.
AB  - We discuss 3 neurophysiological approaches to study auditory verbal
      hallucinations (AVH). First, we describe "state" (or symptom capture) studies
      where periods with and without hallucinations are compared "within" a patient.
      These studies take 2 forms: passive studies, where brain activity during these
      states is compared, and probe studies, where brain responses to sounds during
      these states are compared. EEG (electroencephalography) and MEG
      (magnetoencephalography) data point to frontal and temporal lobe activity, the
      latter resulting in competition with external sounds for auditory resources.
      Second, we discuss "trait" studies where EEG and MEG responses to sounds are
      recorded from patients who hallucinate and those who do not. They suggest a
      tendency to hallucinate is associated with competition for auditory processing
      resources. Third, we discuss studies addressing possible mechanisms of AVH,
      including spontaneous neural activity, abnormal self-monitoring, and
      dysfunctional interregional communication. While most studies show differences in
      EEG and MEG responses between patients and controls, far fewer show symptom
      relationships. We conclude that efforts to understand the pathophysiology of AVH
      using EEG and MEG have been hindered by poor anatomical resolution of the EEG and
      MEG measures, poor assessment of symptoms, poor understanding of the phenomenon,
      poor models of the phenomenon, decoupling of the symptoms from the
      neurophysiology due to medications and comorbidites, and the possibility that the
      schizophrenia diagnosis breeds truer than the symptoms it comprises. These
      problems are common to studies of other psychiatric symptoms and should be
      considered when attempting to understand the basic neural mechanisms responsible
      for them.

PMID- 22368238
TI  - Advances in breath odor research: re-evaluation and newly-arising sciences.

PMID- 22368237
TI  - D-cycloserine: an evolving role in learning and neuroplasticity in schizophrenia.
AB  - As a partial agonist at the glycine site of the NMDA receptor, D-cycloserine
      (DCS) has been viewed as lacking potency to fully test the NMDA receptor
      hypofunction theory of schizophrenia. However, findings of full agonist activity
      at a subset of NMDA receptors that may have particular relevance to
      schizophrenia, plus a growing body of evidence demonstrating enhancement of
      learning and neuroplasticity in animal models, suggest novel therapeutic
      strategies with DCS in schizophrenia. Preliminary studies with once-weekly
      administration have supported this potential new role for DCS in schizophrenia by
      demonstrating benefit for negative symptoms, memory consolidation, and
      facilitation of cognitive behavioral therapy for delusions.

PMID- 22368239
TI  - Reduction of bacterial volatile sulfur compound production by licoricidin and
      licorisoflavan A from licorice.
AB  - Halitosis affects a large proportion of the population and is, in most cases,
      caused by the production of volatile sulfur compounds (VSCs), particularly methyl
      mercaptan and hydrogen sulfide, by specific bacterial species colonizing the oral
      cavity. In this study, a supercritical extract of Chinese licorice (Glycyrrhiza
      uralensis), and its major isoflavans, licoricidin and licorisoflavan A, were
      investigated for their effect on growth, VSC production and protease activity of
      Porphyromonas gingivalis, Prevotella intermedia and Solobacterium moorei, which
      have been associated with halitosis. The effects of licorice extract,
      licoricidin, and licorisoflavan A on VSC production in a saliva model were also
      tested. We first showed that licoricidin and licorisoflavan A, and to a lesser
      extent the licorice extract, were effective in inhibiting the growth of all three
      bacterial species, with minimal inhibitory concentrations in the range of 2-80 ug
      ml(-1). The licorice extract and the two isolates licoricidin and licorisoflavan
      A, were able to dose-dependently reduce VSC production by P. gingivalis, Prev.
      intermedia, and S. moorei as well as by a human saliva model. Although the
      extract and isolates did not inhibit the proteolytic activity of bacteria, they
      blocked the conversion of cysteine into hydrogen sulfide by Prev. intermedia.
      Lastly, the deodorizing effects of the licorice extract, licoricidin, and
      licorisoflavan A were demonstrated, as they can neutralize P. gingivalis-derived
      VSCs. Licorisoflavan A (10 ug ml(-1)) was found to be the most effective by
      reducing VSC levels by 50%. Within the limitations of this study, it can be
      concluded that a licorice supercritical extract and its major isoflavans
      (licoricidin and licorisoflavan A) represent natural ingredients with a potential
      for reducing bacterial VSC production and therefore for controlling halitosis.

PMID- 22368241
TI  - Patient characteristics associated with GP referral to the Access to Allied
      Psychological Services Program: a case-control study.
AB  - BACKGROUND: GPs have referred patients for psychological treatment under the
      Better Outcomes in Mental Health Care, Access to Allied Psychological Services
      (ATAPS) Program since 2003. It is not known how GPs might select patients for
      referral. We explored which characteristics identified ATAPS patients compared to
      usual GP patients. METHODS: The study was conducted in GP Access, a Division of
      General Practice (Newcastle and Lower Hunter) in NSW, Australia. It was a case
      control design with 63 cases (ATAPS patients), and 64 controls (GP patients never
      referred to ATAPS). Unadjusted and sequentially adjusted logistic regressions
      were used to identify independent predictors of being an ATAPS case based on
      official referral guidelines: ICD-10 diagnosis of depression or anxiety and
      scores on the K-10 (psychological distress) and DASS-21 (psychological symptoms).
      A multivariable logistic regression was also used to determine the best minimum
      set of predictor variables. RESULTS: Eight-three per cent of ATAPS cases had
      anxiety or depression. In unadjusted models, any mood disorder, OR 7.68 (95% CI:
      3.47, 17.01), any anxiety disorder, OR 2.88 (95% CI: 1.37, 6.05), higher K-10
      score, OR 1.06 (95% CI: 1.04, 1.14) and higher DASS-21 score, OR 1.06 (95% CI:
      1.03, 1.09) were associated with being an ATAPS case. Any mood disorder, any
      anxiety disorder, K-10 score and DASS-21 scores remained significant in most
      adjusted analyses and all models showed change when adjusted for mental
      disability and physical disability. Three variables predicted being an ATAPS case
      in the multivariable regression: greater mental disability, lesser physical
      disability and greater number of substances misused. CONCLUSION: Cases had higher
      levels of mental disability and greater substance misuse, but lower levels of
      physical disability. This may reflect GP referral decision making and have
      implications for policy development.

PMID- 22368240
TI  - Size and shape of the caudate nucleus in individuals with bipolar affective
      disorder.
AB  - OBJECTIVE: The caudate nucleus (CN) is a crucial component of the ventral
      striatum, which is part of a prefrontal-striatal-thalamic circuit that is
      modulated by limbic structures to subserve emotional processing. Bipolar disorder
      is thought to be underpinned by dysfunctional anterior limbic networks, although
      MRI studies examining the CN have shown equivocal results. As gross volumetric
      analyses may not detect subtle regional change, we aimed to clarify the role of
      the CN in bipolar disorder by undertaking shape analysis to detect regional
      reductions. METHODS: The CN was manually traced on MRI scans from 27 patients
      with bipolar-I disorder and 24 matched controls. A non-parametric spherical
      harmonic shape analysis was undertaken using the SPHARM toolkit. RESULTS: Whilst
      the left CN volume was consistently larger in the sample, there was no effect of
      group or gender or significant interactions between these variables. Volume did
      not correlate with illness duration or lithium dosage, but was larger in those
      with a history of psychosis at trend level. However, left caudate shape differed
      significantly between groups, with deflation in an area along the ventromedial
      surface (connecting to dorsolateral prefrontal regions) in bipolar patients.
      Psychotic patients showed increases in the dorsal head and body at trend level
      overall, in regions connecting to medial and orbitofrontal regions. CONCLUSIONS:
      These findings suggest that subtle rather than gross structural changes occur in
      the CN, which may not be detectable by volumetric analysis alone, and reflect
      alterations in specific frontostriatal circuitry in the disorder.

PMID- 22368242
TI  - Does giving up substance use work for patients with psychosis? A systematic meta
      analysis.
AB  - OBJECTIVE: To assess the extent to which ceasing the use of cannabis or other
      substances reduces the symptoms and social disability associated with psychotic
      illness. METHODS: The electronic databases CINAHL, EMBASE, MEDLINE and PsycINFO
      were searched for peer-reviewed publications in English that report data about
      the characteristics of current and former substance-using patients diagnosed with
      psychotic illnesses. The searches yielded 328 articles, of which 23 studies met
      the inclusion criteria. Four key outcome variables; positive symptoms, negative
      symptoms, ratings of depression and global function, and five other measures of
      outcome that were reported in five or more studies were examined using meta
      analysis. RESULTS: Current substance-using patients were significantly younger
      than former substance-using patients (standardised mean difference (SMD) = 
      0.38), but did not differ in age at onset of psychosis, sex, level of education
      or marital status. Current substance users had higher scores on rating scales of
      positive symptoms (SMD = 0.29) and depression (SMD = 0.36), and lower scores on
      global function (SMD = -0.26) when compared with former substance users. There
      was a significant improvement in the ratings of positive symptoms, mood and
      global function among patients who stopped using substances during the first
      episode of psychosis, while improvements in the symptoms of patients with a more
      established psychotic illness did not reach statistical significance. CONCLUSION:
      The results suggest that substance use contributes to both the symptoms and the
      burden of disability experienced by patients with psychosis. Patients in the
      early stages of psychotic illness should be informed about the benefits of giving
      up substances earlier, rather than later in the illness. Psychiatric services
      should regard the treatment of substance use as an integral part of the treatment
      of psychotic disorders.

PMID- 22368243
TI  - Oases: robust de novo RNA-seq assembly across the dynamic range of expression
      levels.
AB  - MOTIVATION: High-throughput sequencing has made the analysis of new model
      organisms more affordable. Although assembling a new genome can still be costly
      and difficult, it is possible to use RNA-seq to sequence mRNA. In the absence of
      a known genome, it is necessary to assemble these sequences de novo, taking into
      account possible alternative isoforms and the dynamic range of expression values.
      RESULTS: We present a software package named Oases designed to heuristically
      assemble RNA-seq reads in the absence of a reference genome, across a broad
      spectrum of expression values and in presence of alternative isoforms. It
      achieves this by using an array of hash lengths, a dynamic filtering of noise, a
      robust resolution of alternative splicing events and the efficient merging of
      multiple assemblies. It was tested on human and mouse RNA-seq data and is shown
      to improve significantly on the transABySS and Trinity de novo transcriptome
      assemblers. AVAILABILITY AND IMPLEMENTATION: Oases is freely available under the
      GPL license at www.ebi.ac.uk/~zerbino/oases/.

PMID- 22368244
TI  - A new statistical approach to detecting differentially methylated loci for case
      control Illumina array methylation data.
AB  - MOTIVATION: As an epigenetic alteration, DNA methylation plays an important role
      in epigenetic controls of gene transcription. Recent advances in genome-wide scan
      of DNA methylation provide great opportunities in studying the impact of DNA
      methylation on many human diseases including various types of cancer. Due to the
      unique feature of this type of data, applicable statistical methods are limited
      and new sophisticated approaches are desirable. RESULTS: In this article, we
      propose a new statistical test to detect differentially methylated loci for case
      control methylation data generated by Illumina arrays. This new method utilizes
      the important finding that DNA methylation is highly correlated with age. The
      proposed method estimates the overall P-value by combining the P-values from
      independent individual tests each for one age group. Through real data
      application and simulation study, we show that the proposed test is robust and
      usually more powerful than other methods.

PMID- 22368245
TI  - A Bayesian approach to targeted experiment design.
AB  - MOTIVATION: Systems biology employs mathematical modelling to further our
      understanding of biochemical pathways. Since the amount of experimental data on
      which the models are parameterized is often limited, these models exhibit large
      uncertainty in both parameters and predictions. Statistical methods can be used
      to select experiments that will reduce such uncertainty in an optimal manner.
      However, existing methods for optimal experiment design (OED) rely on assumptions
      that are inappropriate when data are scarce considering model complexity.
      RESULTS: We have developed a novel method to perform OED for models that cope
      with large parameter uncertainty. We employ a Bayesian approach involving
      importance sampling of the posterior predictive distribution to predict the
      efficacy of a new measurement at reducing the uncertainty of a selected
      prediction. We demonstrate the method by applying it to a case where we show that
      specific combinations of experiments result in more precise predictions.
      AVAILABILITY AND IMPLEMENTATION: Source code is available at:
      http://bmi.bmt.tue.nl/sysbio/software/pua.html.

PMID- 22368246
TI  - R/DWD: distance-weighted discrimination for classification, visualization and
      batch adjustment.
AB  - R/DWD is an extensible package for classification. It is built based on a
      recently developed powerful classification method called distance weighted
      discrimination (DWD). DWD is related to, and has been shown to be superior to,
      the support vector machine in situations that are fundamental to bioinformatics,
      such as very high dimensional data. DWD has proven to be very useful for several
      fundamental bioinformatics tasks, including classification, data visualization
      and removal of biases, such as batch effects. Earlier DWD implementations,
      however, relied on Matlab, which is not free and requires a license. The major
      contribution of the R/DWD package is an implementation that is completely in R
      and thus can be used without any requirements for licensing or software purchase.
      In addition, R/DWD also provides efficient solvers for second-order-cone
      programming and quadratic programming. AVAILABILITY AND IMPLEMENTATION: The
      package is freely available from cran.r-project.org.

PMID- 22368247
TI  - SiteComp: a server for ligand binding site analysis in protein structures.
AB  - MOTIVATION: Computational characterization of ligand-binding sites in proteins
      provides preliminary information for functional annotation, protein design and
      ligand optimization. SiteComp implements binding site analysis for comparison of
      binding sites, evaluation of residue contribution to binding sites and
      identification of sub-sites with distinct molecular interaction properties.
      AVAILABILITY AND IMPLEMENTATION: The SiteComp server and tutorials are freely
      available at http://sitecomp.sanchezlab.org.

PMID- 22368248
TI  - Unipro UGENE: a unified bioinformatics toolkit.
AB  - Unipro UGENE is a multiplatform open-source software with the main goal of
      assisting molecular biologists without much expertise in bioinformatics to
      manage, analyze and visualize their data. UGENE integrates widely used
      bioinformatics tools within a common user interface. The toolkit supports
      multiple biological data formats and allows the retrieval of data from remote
      data sources. It provides visualization modules for biological objects such as
      annotated genome sequences, Next Generation Sequencing (NGS) assembly data,
      multiple sequence alignments, phylogenetic trees and 3D structures. Most of the
      integrated algorithms are tuned for maximum performance by the usage of
      multithreading and special processor instructions. UGENE includes a visual
      environment for creating reusable workflows that can be launched on local
      resources or in a High Performance Computing (HPC) environment. UGENE is written
      in C++ using the Qt framework. The built-in plugin system and structured UGENE
      API make it possible to extend the toolkit with new functionality. AVAILABILITY
      AND IMPLEMENTATION: UGENE binaries are freely available for MS Windows, Linux and
      Mac OS X at http://ugene.unipro.ru/download.html. UGENE code is licensed under
      the GPLv2; the information about the code licensing and copyright of integrated
      tools can be found in the LICENSE.3rd_party file provided with the source bundle.

PMID- 22368249
TI  - Standardization of clinical protocols in oral malodor research.
AB  - The objective of this study is to standardize protocols for clinical research
      into oral malodor caused by volatile sulfur compounds (VSCs). To detect VSCs, a
      gas chromatograph (GC) using a flame photometric detector equipped with a
      bandpass filter (at 393 nm) is the gold standard (sensitivity: 5 * 10(-11) gS s(
      1)). The baselines of VSC concentrations in mouth air varied considerably over a
      week. When the subjects refrained from eating, drinking and oral hygiene
      including mouth rinsing, the VSC concentrations remained constant until eating.
      Over a 6 h period after a meal, VSC concentrations decreased dramatically (p <
      0.01). These results point to optimal times and conditions for sampling subjects.
      Several portable devices were compared with the measurements by the GCs. Portable
      GCs demonstrated capabilities similar to those of the GCs. We also applied the
      recommended protocols described below to clinical research testing the efficacy
      of ZnCl(2) products, and confirmed that using the recommended protocols in a
      randomized crossover design would provide very clear results. Proposed protocols
      include: (a) a short-term study rather than a long-term study is strongly
      recommended, since the VSC concentrations are constant in the short term; (b) a
      crossover study would be the best design to avoid the effects of individual
      specificities on each clinical intervention; (c) measurements of VSCs should
      preferably be carried out using either a GC or portable GCs.

PMID- 22368250
TI  - A possibility of a protein-bound water molecule as the ionizable group
      responsible for pKe at the alkaline side in human matrix metalloproteinase 7
      activity.
AB  - Human matrix metalloproteinase 7 (MMP-7) activity exhibits broad bell-shaped pH
      profile with the acidic and alkaline pK(a) (pK(e1) and pK(e2)) values of about 4
      and 10. The ionizable group for pK(e2) was assigned to Lys or Arg by
      thermodynamic analysis; however, no such residues are present in the active site.
      Hence, based on the crystal structure, we hypothesized that a water molecule
      bound to the main-chain nitrogen of Ala162 (W1) or the main-chain carbonyl oxygen
      of Pro217 (W2) is a candidate for the ionizable group for pK(e2) [Takeharu, H. et
      al. (2011) Biochim. Biophys. Acta 1814, 1940-1946]. In this study, we inspected
      this hypothesis. In the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu
      Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-L-Ala-L-Arg-NH(2),
      all 19 variants, in which one of all Lys and Arg residues was replaced by Ala,
      retained activity, indicating that neither Lys nor Arg is the ionizable group.
      pK(e2) values of A162S, A162V and A162G were 9.6 +/- 0.1, 9.5 +/- 0.1 and 10.4 +/
      0.2, respectively, different from that of wild-type MMP-7 (WT) (9.9 +/- 0.1) by
      0.3-0.5 pH unit, and those of P217S, P217V and P217G were 10.1 +/- 0.1, 9.8 +/-
      0.1 and 9.7 +/- 0.1, respectively, different from that of WT by 0.1-0.2 pH unit.
      These results suggest a possibility of W1 or W2 as the ionizable group for
      pK(e2).

PMID- 22368251
TI  - Halitosis and Helicobacter pylori infection.
AB  - There is disagreement about a possible relationship between Helicobacter pylori
      (H. pylori) infection and objective halitosis, as established by volatile sulfur
      compounds (VSCs) in the breath. Many studies related to H. pylori used self
      reported halitosis, a subjective and unreliable method to detect halitosis. In
      this study a possible relation between H. pylori and halitosis was evaluated,
      using an objective method (gas chromatography, GC) to detect the VSCs,
      responsible for the halitosis. The levels of the VSCs hydrogen sulfide (H(2)S),
      methyl mercaptan (MM) and dimethyl sulfide (DMS) were measured in mouth breath
      and in stomach air of 11 H. pylori positive patients and of 38 H. pylori negative
      patients, all with gastric pathology. Halitosis was also established by
      organoleptic scoring (OLS) of mouth-breath. The levels of H(2)S, MM and DMS in
      the mouth-breath and stomach air of the H. pylori positive patients did not
      differ significantly from those of the H. pylori negative patients. OLS of the
      mouth-breath resulted in 9 patients with halitosis, 1 out of the H. pylori
      positive group and 8 out of the H. pylori negative group, which is not
      statistically different. The concentrations of the VSCs in stomach air were in
      nearly all cases below the thresholds of objectionability of the various VSCs,
      indicating that halitosis does not originate in the stomach. The patients with
      gastric pathology were also compared with control patients without gastric
      pathology and with normal volunteers. No significant differences in VSCs in mouth
      breath were observed between these groups. Thus, in this study no association
      between halitosis and H. pylori infection was found. Halitosis, as established by
      GC and OLS, nearly always originates within the oral cavity and seldom or never
      within the stomach.

PMID- 22368252
TI  - Sequence requirements for RNA binding by HuR and AUF1.
AB  - The stability of RNAs bearing AU-rich elements in their 3'-UTRs, and thus the
      level of expression of their protein products, is regulated by interactions with
      cytoplasmic RNA-binding proteins. Binding by HuR generally leads to mRNA
      stabilization and increased protein production, whereas binding by AUF1 isoforms
      generally lead to rapid degradation of the mRNA and reduced protein production.
      The exact nature of the interplay between these and other RNA-binding proteins
      remains unclear, although recent studies have shown close interactions between
      them and even suggested competition between the two for binding to their cognate
      recognition sequences. Other recent reports have suggested that the sequences
      recognized by the two proteins are different. We therefore performed a detailed
      in vitro analysis of the binding site(s) for HuR and AUF1 present in androgen
      receptor mRNA to define their exact target sequences, and show that the same
      sequence is contacted by both proteins. Furthermore, we analysed a proposed HuR
      target within the 3'-UTR of MTA1 mRNA, and show that the contacted bases lie
      outside of the postulated motif and are a better match to a classical ARE than
      the postulated motif. The defining features of these HuR binding sites are their
      U-richness and single strandedness.

PMID- 22368253
TI  - Hydrogen sulfide increases hepatic differentiation in tooth-pulp stem cells.
AB  - The toxicity of hydrogen sulfide (H(2)S), an oral malodorous compound, is well
      reported. We have recently established an experimental model of hepatic
      differentiation from human tooth-pulp stem cells (HTPC) using serum-free medium.
      The objective of the present study is to determine the effect of H(2)S on hepatic
      differentiation. The CD117 positive cell fraction was obtained from deciduous
      HTPC using magnetic cell sorting. After 3-4 passages, cells were grown in
      Dulbecco's modified Eagle's medium supplemented with insulin-transferrin-selenium
      x (ITS-x), embryotrophic factor (ETF) and hepatocyte growth factor (HGF) for
      hepatic commitment (five days). For hepatic differentiation the cells were
      cultured in Iscove's modified Dulbecco's medium supplemented with ITS-x, ETF,
      oncostatin, HGF and dexamethasone for 15 days in air containing 5% CO(2), with or
      without H(2)S at 0.05 ng ml(-1). Cells were assayed for the expression of hepatic
      markers alpha-fetoprotein, albumin or carbamoyl phosphate synthetase, and urea
      concentrations and glycogen synthesis were also determined. The panel of hepatic
      markers was expressed more in the test groups exposed to H(2)S than in the
      control groups. Urea and glycogen production were also increased, especially
      glycogen which was approximately five times greater compared to the control (p <
      0.01). We concluded that H(2)S at physiological concentrations increased the
      ability of HTPC to undergo hepatogenic differentiation.

PMID- 22368254
TI  - SED-ED, a workflow editor for computational biology experiments written in SED
      ML.
AB  - The simulation experiment description markup language (SED-ML) is a new community
      data standard to encode computational biology experiments in a computer-readable
      XML format. Its widespread adoption will require the development of software
      support to work with SED-ML files. Here, we describe a software tool, SED-ED, to
      view, edit, validate and annotate SED-ML documents while shielding end-users from
      the underlying XML representation. SED-ED supports modellers who wish to create,
      understand and further develop a simulation description provided in SED-ML
      format. AVAILABILITY AND IMPLEMENTATION: SED-ED is available as a standalone Java
      application, as an Eclipse plug-in and as an SBSI (www.sbsi.ed.ac.uk) plug-in,
      all under an MIT open-source license. Source code is at https://sed-ed
      sedmleditor.googlecode.com/svn. The application itself is available from
      https://sourceforge.net/projects/jlibsedml/files/SED-ED/.

PMID- 22368255
TI  - High-quality sequence clustering guided by network topology and multiple
      alignment likelihood.
AB  - MOTIVATION: Proteins can be naturally classified into families of homologous
      sequences that derive from a common ancestor. The comparison of homologous
      sequences and the analysis of their phylogenetic relationships provide useful
      information regarding the function and evolution of genes. One important
      difficulty of clustering methods is to distinguish highly divergent homologous
      sequences from sequences that only share partial homology due to evolution by
      protein domain rearrangements. Existing clustering methods require parameters
      that have to be set a priori. Given the variability in the evolution pattern
      among proteins, these parameters cannot be optimal for all gene families.
      RESULTS: We propose a strategy that aims at clustering sequences homologous over
      their entire length, and that takes into account the pattern of substitution
      specific to each gene family. Sequences are first all compared with each other
      and clustered into pre-families, based on pairwise similarity criteria, with
      permissive parameters to optimize sensitivity. Pre-families are then divided into
      homogeneous clusters, based on the topology of the similarity network. Finally,
      clusters are progressively merged into families, for which we compute multiple
      alignments, and we use a model selection technique to find the optimal tradeoff
      between the number of families and multiple alignment likelihood. To evaluate
      this method, called HiFiX, we analyzed simulated sequences and manually curated
      datasets. These tests showed that HiFiX is the only method robust to both
      sequence divergence and domain rearrangements. HiFiX is fast enough to be used on
      very large datasets. AVAILABILITY AND IMPLEMENTATION: The Python software HiFiX
      is freely available at http://lbbe.univ-lyon1.fr/hifix.

PMID- 22368256
TI  - The role of p53 in an apoptotic process caused by an oral malodorous compound in
      periodontal tissues: a review.
AB  - Oral malodor is caused by volatile sulfur compounds (VSCs) composed mainly of
      hydrogen sulfide (H(2)S) and methyl mercaptan. In particular, H(2)S is an
      important compound, since it is a major component of physiologic halitosis. The
      toxicity of VSCs is similar to that of hydrogen cyanide, and is well
      investigated. The role of VSCs in reducing collagen in human gingival fibroblasts
      is one of the main sources of their toxicity to human oral tissues. It has been
      reported recently that H(2)S may cause apoptosis in several periodontal tissues.
      In human gingival fibroblasts, H(2)S inhibits not only cytochrome c oxidase
      activity but also superoxide dismutase activity. The levels of reactive oxygen
      species are markedly increased, which causes the release of cytochrome c into the
      cytoplasm, resulting in caspase-9 activation; finally, the executor caspase,
      caspase-3, is activated. This pathway is commonly observed in cells from all
      periodontal tissues. Moreover, p53, an apoptotic factor, and phosphorlylated p53,
      which is the activated form, are increased by H(2)S in keratinocyte stem cells
      and osteoblasts. H(2)S also increases the expression of Bax, a primary response
      gene playing an important role in p53-mediated apoptosis, but maintains a lower
      expression of Bcl-2, an anti-apoptotic factor, in osteoblasts. It is concluded
      that the Bax apoptotic pathway and the mitochondrial pathway are activated by
      H(2)S.

PMID- 22368258
TI  - Breaking paradigms: a new definition for halitosis in the context of pseudo
      halitosis and halitophobia.
AB  - It is known that almost one-third of patients who seeks treatment for bad breath
      do not have genuine halitosis. Halitosis can occur even in cases when the malodor
      is not perceived by those around the patient and can neither be confirmed by
      organoleptic tests, nor by sulfur portable monitor readings. In such cases, these
      patients have been considered as halitophobic or have pseudo-halitosis. The
      complaint might signal the existence of a chemosensory dysfunction. Factors
      associated with taste and smell perception can be potentially connected to the
      occurrence of oral malodor. The threshold values of volatile sulfur compounds
      that have been used to establish the diagnosis of genuine halitosis do not take
      into account that the patient may perceive low levels of these and of other
      volatile compounds through retronasal olfaction. The current concept of halitosis
      requires the presence of a signal that has been based on equipment results, from
      the olfactory perception of the examiners and of those who interact with the
      patient. Nevertheless, the concept does not encompass the symptoms of halitosis.
      This paper addresses some of the possible causes of chemosensory dysfunction and
      proposes a new definition for halitosis.

PMID- 22368259
TI  - Effects of oil drops containing Lactobacillus salivarius WB21 on periodontal
      health and oral microbiota producing volatile sulfur compounds.
AB  - The objective of this paper is to evaluate the effects of oil drops containing
      Lactobacillus salivarius WB21 on periodontal health and oral microbiota producing
      volatile sulfur compounds (VSCs). For this study, 42 subjects were randomly
      assigned to receive oil samples containing L. salivarius WB21 or a placebo for
      two weeks. Oral assessment and saliva collection were performed on days 1 and 15.
      Bacterial analysis was performed using the real-time polymerase chain reaction
      and terminal restriction fragment length polymorphism (T-RFLP). In both the
      experimental and placebo groups, the average probing depth, number of periodontal
      pockets, and the percentage of bleeding on probing (BOP) decreased while
      stimulated salivary flow increased on day 15. BOP was reduced in the experimental
      group compared with the placebo group (P = 0.010). In the experimental group,
      total bacterial numbers decreased, and the number of L. salivarius increased. The
      number of Prevotella intermedia, which is correlated with hydrogen sulfide
      concentration in mouth air, increased in the placebo group and did not change in
      the experimental group. T-RFLP analysis found that the peak area proportions
      representing Porphyromonas gingivalis, P. intermedia, Tannerella forsythensis,
      and Fusobacterium nucleatum decreased in the experimental group, although there
      was no significant change in the bacterial composition. Thus we observed oil
      drops containing L. salivarius WB21 improved BOP and inhibited the reproduction
      of total and VSC-producing periodontopathic bacteria compared with the placebo
      group, but also showed the limit of its efficacy in controlling VSCs producing
      and periodontal pathogens.

PMID- 22368260
TI  - Tablets containing a cysteine protease, actinidine, reduce oral malodor: a
      crossover study.
AB  - Tongue coating (TC) mainly consists of protein mostly from exfoliated epithelial
      cells. Until now, to reduce TC accumulation, only mechanical measures have been
      available, and the procedure involves unpleasant side effects, such as gagging
      reflex or carcinogenesis related to mechanical stimulation. We expected that
      protease might be effective in reducing the accumulation of TC causing oral
      malodor. The purpose of this study was to determine the effect of long-term use
      of candy tablets containing protease, actinidine, on both TC accumulation and
      concentration of volatile sulfur compounds (VSCs) in mouth air. We employed 14
      subjects aged 24 to 54 years old for this study, and conducted a double-blind
      randomized crossover trial. The subjects sucked the tablets containing actinidine
      three times a day until the sixth day after starting the study. The tablets
      without actinidine were utilized as a placebo. Measurements of VSC concentration
      and TC accumulation were carried out before and after chewing tablets on the
      first day, and also on the seventh day. The levels of VSC and TC significantly (p
      < 0.05) decreased after tablets were taken on the first day in both the test and
      placebo groups. There was a statistically significant decrease (p < 0.05) in VSC
      after seven days of use only in the test group. The results of the study suggest
      that the tablets containing  actinidine had an accumulative effect in reducing
      VSC in mouth air with long-term use.

PMID- 22368261
TI  - Combined intravitreal and subconjunctival carboplatin for retinoblastoma with
      vitreous seeds.
AB  - BACKGROUND: To describe the technique of intravitreal chemotherapy preceded by
      subconjunctival chemotherapy for the treatment of vitreous seeds in advanced
      stage retinoblastoma. METHODS: This non-comparative interventional case series
      retrospectively reviewed the medical records and postenucleation
      histopathological findings of two patients who presented within weeks of each
      other with bilateral retinoblastoma, Reese-Ellsworth (R-E) stage Vb in the worse
      eye. Both patients had failed systemic chemotherapy prior to receiving a single
      treatment of 0.5 ml (5 mg per 0.5 ml) of subconjunctival carboplatin, through
      which 0.05 ml (3 mcg per 0.05 ml) of carboplatin was injected into the vitreous
      (Case 2 received 0.1 ml of intravitreal carboplatin). The subconjunctival
      chemotherapy was given to reduce the risk of orbital tumour seeding following
      intravitreal injection. Following enucleation, ocular toxicity and the presence
      or absence of viable tumour cells at the intravitreal injection site were
      recorded. RESULTS: Histopathological examination did not reveal patency of the
      pars plana intravitreal penetration site in either case at 6 weeks post-treatment
      nor was malignant seeding detected in the area of injection. Examination of the
      two enucleated eyes did not demonstrate structural toxicity to the cornea,
      anterior segment, iris or retina. Additionally, both cases were followed for over
      37 months post-treatment, without the occurrence of orbital malignancy.
      CONCLUSIONS: Injecting a bleb of subconjunctival chemotherapy prior to
      intravitreal drug delivery appeared to mitigate the risk of orbital tumour
      seeding in two patients with advanced stage retinoblastoma. Incorporating this
      technique may allow further investigation of intravitreal chemotherapy for the
      treatment of vitreous seeds in retinoblastoma.

PMID- 22368262
TI  - Profiling safety of intravitreal injections for retinoblastoma using an anti
      reflux procedure and sterilisation of the needle track.
AB  - BACKGROUND: The preservation of globe integrity has always been a major concern
      during the treatment of retinoblastoma for fear of extraocular or metastatic
      spread. Intravitreal chemotherapy has been attempted as a desperate salvage
      therapy only for eyes with refractory retinoblastoma. Published data on the
      safety and efficacy of this route are, however, limited. METHODS: A modified
      technique of intravitreal injection in eyes with retinoblastoma is described. All
      children with retinoblastoma who received one or more intravitreal injections
      using this technique were retrospectively reviewed concerning ocular
      complications of the injection procedure as well as clinical or histopathological
      evidence of tumour spread. RESULTS: 30 eyes of 30 children with retinoblastoma
      received a total of 135 intravitreal injections, with a median follw-up duration
      of 13.5 months. No extraocular spread was seen on clinical follow-up in any
      patients and there was no tumour contamination of the retrieved entry sites
      histopathologically analysed among the five enucleated eyes. No significant
      ocular side effects were observed except transient localised vitreous haemorrhage
      (3/135). CONCLUSION: This technique is potentially safe and effective at a low
      cost and may play a promising role, especially in the treatment of recurrent
      and/or resistant vitreous disease in retinoblastoma, as an alternative to
      enucleation and/or external beam radiotherapy. However, this treatment should not
      replace the primary standard of care of retinoblastoma and should not be
      considered in group E eyes. Its application should be approved by an
      ophthalmological-oncological team and it should be performed by an experienced
      eye surgeon in a tertiary referral centre after careful selection of a tumour
      free injection site.

PMID- 22368263
TI  - The effect on quality of life of long-term botulinum toxin A injections to
      maintain ocular alignment in adult patients with strabismus.
AB  - BACKGROUND: There is considerable evidence to show that strabismus patients
      report their quality of life (QoL) as lower than normal controls. While the
      majority of patients with strabismus are treated with surgery there are a number
      of cases where surgery is not possible and good long-term ocular alignment can be
      maintained with repeated injections of botulinum toxin. METHODS: 65 patients who
      had undergone over 25 injections of botulinum toxin A for long-term control of
      their deviation were identified and asked to fill in and return the Adult
      Strabismus questionnaire (AS-20) to assess their QoL. RESULTS: 46 questionnaires
      were available for analysis. The mean AS-20 score in our patients compared
      favourably with that reported for normal controls and was much higher than that
      reported for patients with strabismus. CONCLUSION: Long-term injections with
      botulinum toxin A is a good treatment for maintaining ocular alignment if squint
      surgery is not indicated and those patients receiving treatment score near the
      level of normal controls in QoL terms.

PMID- 22368264
TI  - A neonate with seizures.

PMID- 22368265
TI  - A teenager with pustular lesions on the hands and feet.

PMID- 22368266
TI  - Ramipril and telmisartan exhibit differential effects in cardiac pressure
      overload-induced hypertrophy without an additional benefit of the combination of
      both drugs.
AB  - OBJECTIVES: We aimed to characterize different cellular effects of angiotensin
      converting enzyme inhibitors (ACEIs) and angiotensin 1 (AT1) receptor blockers
      (ARBs) as mono- or combination therapy in cardiac pressure overload.  Methods and
      RESULTS: C57B1/6 mice received either the ACEI ramipril (2.5 mg/kg body weight),
      the ARB telmisartan (20 mg/kg body weight), or the combination. In all groups,
      pressure overload was induced by transverse aortic constriction (TAC). Cardiac
      hypertrophy (heart weight/tibia length) induced by TAC was reduced in all 3
      treatment groups, with the most pronounced effect in the telmisartan group. The
      cardiomyocyte short-axis diameter and cardiac fibrosis were increased by TAC and
      similarly reduced by ACEI, ARB, and the combination therapy. The TAC-induced
      increase in the number of proliferating Ki67(pos) cardiomyocytes and
      noncardiomyocytes was reduced more potently by ACEI than by ARB. Four days of
      drug treatment induced a significant increase in Scal(pos)/VEGFR1(pos)
      endothelial progenitor cells (EPCs) in all animals in the treated SHAM groups.
      After 1 day of aortic constriction, only ramipril increased EPC numbers; after 5
      weeks, telmisartan monotherapy did not change the EPC levels compared to vehicle
      or the combination therapy but raised it compared to ramipril. Neither TAC nor
      one of the therapies changed the number of cardiac capillaries per
      cardiomyocytes. CONCLUSIONS: ACE inhibition and AT1 receptor blockade have
      beneficial effects in remodeling processes during cardiac pressure overload.
      There are small differences between the 2 therapeutical approaches, but the
      combination therapy has no additional benefit.

PMID- 22368267
TI  - Current status of lung transplantation.
AB  - Lung transplantation is a well-established treatment option for selected patients
      with end-stage lung disease, leading to improved survival and improved quality of
      life. The last 20 years have seen a steady growth in number of lung
      transplantation procedures performed worldwide. The increase in clinical activity
      has been associated with tremendous progress in the understanding of cellular and
      molecular processes that limit both short- and long-term outcomes. This review
      gives a comprehensive overview of the current status of lung transplantation for
      the referring physician. It demonstrates that careful selection of potential
      recipients, optimisation of their condition prior to transplant, use of carefully
      assessed donor organs, excellent surgery and meticulous long-term follow-up are
      all essential ingredients in determining a successful outcome.

PMID- 22368269
TI  - A-Z of nutritional supplements: dietary supplements, sports nutrition foods and
      ergogenic aids for health and performance--Part 30.

PMID- 22368268
TI  - HD2C interacts with HDA6 and is involved in ABA and salt stress response in
      Arabidopsis.
AB  - HD2 proteins are plant specific histone deacetylases. Four HD2 proteins, HD2A,
      HD2B, HD2C, and HD2D, have been identified in Arabidopsis. It was found that the
      expression of HD2A, HD2B, HD2C, and HD2D was repressed by ABA and NaCl. To
      investigate the function of HD2 proteins further, two HD2C T-DNA insertion lines
      of Arabidopsis, hd2c-1 and hd2c-3 were identified. Compared with wild-type
      plants, hd2c-1 and hd2c-3 plants displayed increased sensitivity to ABA and NaCl
      during germination and decreased tolerance to salt stress. These observations
      support a role of HD2C in the ABA and salt-stress response in Arabidopsis.
      Moreover, it was demonstrated that HD2C interacted physically with a RPD3-type
      histone deacetylase, HDA6, and bound to histone H3. The expression of ABA
      responsive genes, ABI1 and ABI2, was increased in hda6, hd2c, and hda6/hd2c-1
      double mutant plants, which was associated with increased histone H3K9K14
      acetylation and decreased histone H3K9 dimethylation. Taken together, our results
      suggested that HD2C functionally associates with HDA6 and regulates gene
      expression through histone modifications.

PMID- 22368270
TI  - Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial
      outcome and mechanisms of subsequent nonresponsiveness associated with the
      emergence of a D835 mutation.
AB  - Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 (FLT3)
      gene occurs in 30% of acute myeloid leukemias (AMLs) and confers a poor
      prognosis. Thirteen relapsed or chemo-refractory FLT3-ITD(+) AML patients were
      treated with sorafenib (200-400 mg twice daily). Twelve patients showed clearance
      or near clearance of bone marrow myeloblasts after 27 (range 21-84) days with
      evidence of differentiation of leukemia cells. The sorafenib response was lost in
      most patients after 72 (range 54-287) days but the FLT3 and downstream effectors
      remained suppressed. Gene expression profiling showed that leukemia cells that
      have become sorafenib resistant expressed several genes including ALDH1A1, JAK3,
      and MMP15, whose functions were unknown in AML. Nonobese diabetic/severe combined
      immunodeficiency mice transplanted with leukemia cells from patients before and
      during sorafenib resistance recapitulated the clinical results. Both ITD and
      tyrosine kinase domain mutations at D835 were identified in leukemia initiating
      cells (LICs) from samples before sorafenib treatment. LICs bearing the D835
      mutant have expanded during sorafenib treatment and dominated during the
      subsequent clinical resistance. These results suggest that sorafenib have
      selected more aggressive sorafenib-resistant subclones carrying both FLT3-ITD and
      D835 mutations, and might provide important leads to further improvement of
      treatment outcome with FLT3 inhibitors.

PMID- 22368271
TI  - Role of bone marrow transplantation for correcting hemophilia A in mice.
AB  - To better understand cellular basis of hemophilia, cell types capable of
      producing FVIII need to be identified. We determined whether bone marrow (BM)
      derived cells would produce cells capable of synthesizing and releasing FVIII by
      transplanting healthy mouse BM into hemophilia A mice. To track donor-derived
      cells, we used genetic reporters. Use of multiple coagulation assays demonstrated
      whether FVIII produced by discrete cell populations would correct hemophilia A.
      We found that animals receiving healthy BM cells survived bleeding challenge with
      correction of hemophilia, although donor BM-derived hepatocytes or endothelial
      cells were extremely rare, and these cells did not account for therapeutic
      benefits. By contrast, donor BM-derived mononuclear and mesenchymal stromal cells
      were more abundant and expressed FVIII mRNA as well as FVIII protein. Moreover,
      injection of healthy mouse Kupffer cells (liver macrophage/mononuclear cells),
      which predominantly originate from BM, or of healthy BM-derived mesenchymal
      stromal cells, protected hemophilia A mice from bleeding challenge with
      appearance of FVIII in blood. Therefore, BM transplantation corrected hemophilia
      A through donor-derived mononuclear cells and mesenchymal stromal cells. These
      insights into FVIII synthesis and production in alternative cell types will
      advance studies of pathophysiological mechanisms and therapeutic development in
      hemophilia A.

PMID- 22368272
TI  - Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in
      pediatric acute lymphoblastic leukemia: a Children's Oncology Group study.
AB  - As controversy exists regarding the prognostic significance of genomic
      rearrangements of CRLF2 in pediatric B-precursor acute lymphoblastic leukemia
      (ALL) classified as standard/intermediate-risk (SR) or high-risk (HR), we
      assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomic
      lesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes
      frequently associated with high CRLF2 expression (IKZF1, JAK, IL7R), and minimal
      residual disease (MRD) in 1061 pediatric ALL patients (499 HR and 562 SR) on COG
      Trials P9905/P9906. Whereas very high CRLF2 expression was found in 17.5% of
      cases, only 51.4% of high CRLF2 expressors had CRLF2 genomic lesions. The
      mechanism underlying elevated CRLF2 expression in cases lacking known genomic
      lesions remains to be determined. All CRLF2 genomic lesions and virtually all JAK
      mutations were found in high CRLF2 expressors, whereas IKZF1 deletions/mutations
      were distributed across the full cohort. In multivariate analyses, NCI risk
      group, MRD, high CRLF2 expression, and IKZF1 lesions were associated with relapse
      free survival. Within HR ALL, only MRD and CRLF2 expression predicted a poorer
      relapse-free survival; no difference was seen between cases with or without CRLF2
      genomic lesions. Thus, high CRLF2 expression is associated with a very poor
      outcome in high-risk, but not standard-risk, ALL. This study is registered at
      www.clinicaltrials.gov as NCT00005596 and NCT00005603.

PMID- 22368273
TI  - The zebrafish reveals dependence of the mast cell lineage on Notch signaling in
      vivo.
AB  - We used the opportunities afforded by the zebrafish to determine upstream
      pathways regulating mast cell development in vivo and identify their cellular
      origin. Colocalization studies demonstrated zebrafish notch receptor expression
      in cells expressing carboxypeptidase A5 (cpa5), a zebrafish mast cell-specific
      marker. Inhibition of the Notch pathway resulted in decreased cpa5 expression in
      mindbomb mutants and wild-type embryos treated with the gamma-secretase
      inhibitor, Compound E. A series of morpholino knockdown studies specifically
      identified notch1b and gata2 as the critical factors regulating mast cell fate.
      Moreover, hsp70::GAL4;UAS::nicd1a transgenic embryos overexpressing an activated
      form of notch1, nicd1a, displayed increased cpa5, gata2, and pu.1 expression.
      This increase in cpa5 expression could be reversed and reduced below baseline
      levels in a dose-dependent manner using Compound E. Finally, evidence that cpa5
      expression colocalizes with lmo2 in the absence of hematopoietic stem cells
      revealed that definitive mast cells initially delineate from erythromyeloid
      progenitors. These studies identify a master role for Notch signaling in
      vertebrate mast cell development and establish developmental origins of this
      lineage. Moreover, these findings postulate targeting the Notch pathway as a
      therapeutic strategy in mast cell diseases.

PMID- 22368274
TI  - A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity
      by maintenance of regulatory T cells via GITR ligand.
AB  - B cells are important for the regulation of autoimmune responses. In experimental
      autoimmune encephalomyelitis (EAE), B cells are required for spontaneous recovery
      in acute models. Production of IL-10 by regulatory B cells has been shown to
      modulate the severity EAE and other autoimmune diseases. Previously, we suggested
      that B cells regulated the number of CD4(+)Foxp3(+) T regulatory cells (Treg) in
      the CNS during EAE. Because Treg suppress autoimmune responses, we asked whether
      B cells control autoimmunity by maintenance of Treg numbers. B cell deficiency
      achieved either genetically (MUMT) or by depletion with anti-CD20 resulted in a
      significant reduction in the number of peripheral but not thymic Treg. Adoptive
      transfer of WT B cells into MUMT mice restored both Treg numbers and recovery
      from EAE. When we investigated the mechanism whereby B cells induce the
      proliferation of Treg and EAE recovery, we found that glucocorticoid-induced TNF
      ligand, but not IL-10, expression by B cells was required. Of clinical
      significance is the finding that anti-CD20 depletion of B cells accelerated
      spontaneous EAE and colitis. Our results demonstrate that B cells play a major
      role in immune tolerance required for the prevention of autoimmunity by
      maintenance of Treg via their expression of glucocorticoid-induced TNFR ligand.

PMID- 22368275
TI  - Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia.
AB  - Burkholderia cenocepacia is an opportunistic pathogen that causes chronic
      infection and induces progressive respiratory inflammation in cystic fibrosis
      patients. Recognition of bacteria by mononuclear cells generally results in the
      activation of caspase-1 and processing of IL-1beta, a major proinflammatory
      cytokine. In this study, we report that human pyrin is required to detect
      intracellular B. cenocepacia leading to IL-1beta processing and release. This
      inflammatory response involves the host adapter molecule ASC and the bacterial
      type VI secretion system (T6SS). Human monocytes and THP-1 cells stably
      expressing either small interfering RNA against pyrin or YFP-pyrin and ASC (YFP
      ASC) were infected with B. cenocepacia and analyzed for inflammasome activation.
      B. cenocepacia efficiently activates the inflammasome and IL-1beta release in
      monocytes and THP-1. Suppression of pyrin levels in monocytes and THP-1 cells
      reduced caspase-1 activation and IL-1beta release in response to B. cenocepacia
      challenge. In contrast, overexpression of pyrin or ASC induced a robust IL-1beta
      response to B. cenocepacia, which correlated with enhanced host cell death.
      Inflammasome activation was significantly reduced in cells infected with T6SS
      defective mutants of B. cenocepacia, suggesting that the inflammatory reaction is
      likely induced by an as yet uncharacterized effector(s) of the T6SS. Together, we
      show for the first time, to our knowledge, that in human mononuclear cells
      infected with B. cenocepacia, pyrin associates with caspase-1 and ASC forming an
      inflammasome that upregulates mononuclear cell IL-1beta processing and release.

PMID- 22368276
TI  - Exhaustion of cytotoxic effector systems may limit monoclonal antibody-based
      immunotherapy in cancer patients.
AB  - The CD20 mAb ofatumumab (OFA) induces complement-mediated lysis of B cells. In an
      investigator-initiated phase II trial of OFA plus chemotherapy for chronic
      lymphocytic leukemia (CLL), OFA treatment promoted partial CLL B cell depletion
      that coincided with reduced complement titers. Remaining CLL B cells circulated
      with bound OFA and covalently bound complement breakdown product C3d, indicative
      of ongoing complement activation. Presumably, neither complement- nor effector
      cell-based mechanisms were sufficiently robust to clear these remaining B cells.
      Instead, almost all of the bound OFA and CD20 was removed from the cells, in
      accordance with previous clinical studies that demonstrated comparable loss of
      CD20 from B cells after treatment of CLL patients with rituximab. In vitro
      experiments with OFA and rituximab addressing these observations suggest that
      host effector mechanisms that support mAb-mediated lysis and tumor cell clearance
      are finite, and they can be saturated or exhausted at high B cell burdens,
      particularly at high mAb concentrations. Interestingly, only a fraction of
      available complement was required to kill cells with CD20 mAbs, and killing could
      be tuned by titrating the mAb concentration. Consequently, maximal B cell killing
      of an initial and secondary B cell challenge was achieved with intermediate mAb
      concentrations, whereas high concentrations promoted lower overall killing.
      Therefore, mAb therapies that rely substantially on effector mechanisms subject
      to exhaustion, including complement, may benefit from lower, more frequent dosing
      schemes optimized to sustain and maximize killing by cytotoxic immune effector
      systems.

PMID- 22368277
TI  - Properdin is critical for antibody-dependent bactericidal activity against
      Neisseria gonorrhoeae that recruit C4b-binding protein.
AB  - Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, is an
      important cause of morbidity worldwide. A safe and effective vaccine against
      gonorrhea is needed because of emerging resistance of gonococci to almost every
      class of antibiotic. A gonococcal lipooligosaccharide epitope defined by the mAb
      2C7 is being evaluated as a candidate for development of an Ab-based vaccine.
      Immune Abs against N. gonorrhoeae need to overcome several subversive mechanisms
      whereby gonococcus evades complement, including binding to C4b-binding protein
      (C4BP; classical pathway inhibitor) and factor H (alternative pathway [AP]
      inhibitor). The role of AP recruitment and, in particular, properdin in assisting
      killing of gonococci by specific Abs is the subject of this study. We show that
      only those gonococcal strains that bind C4BP require properdin for killing by
      2C7, whereas strains that do not bind C4BP are efficiently killed by 2C7 even
      when AP function is blocked. C3 deposition on bacteria mirrored killing.
      Recruitment of the AP by mAb 2C7, as measured by factor B binding, occurred in a
      properdin-dependent manner. These findings were confirmed using isogenic mutant
      strains that differed in their ability to bind to C4BP. Immune human serum that
      contained bactericidal Abs directed against the 2C7 lipooligosaccharide epitope
      as well as murine antigonococcal antiserum required functional properdin to kill
      C4BP-binding strains, but not C4BP-nonbinding strains. Collectively, these data
      point to an important role for properdin in facilitating immune Ab-mediated
      complement-dependent killing of gonococcal strains that inhibit the classical
      pathway by recruiting C4BP.

PMID- 22368278
TI  - Obligate symbionts activate immune system development in the tsetse fly.
AB  - Many insects rely on the presence of symbiotic bacteria for proper immune system
      function. However, the molecular mechanisms that underlie this phenomenon are
      poorly understood. Adult tsetse flies (Glossina spp.) house three symbiotic
      bacteria that are vertically transmitted from mother to offspring during this
      insect's unique viviparous mode of reproduction. Larval tsetse that undergo
      intrauterine development in the absence of their obligate mutualist,
      Wigglesworthia, exhibit a compromised immune system during adulthood. In this
      study, we characterize the immune phenotype of tsetse that develop in the absence
      of all of their endogenous symbiotic microbes. Aposymbiotic tsetse (Glossina
      morsitans morsitans [Gmm(Apo)]) present a severely compromised immune system that
      is characterized by the absence of phagocytic hemocytes and atypical expression
      of immunity-related genes. Correspondingly, these flies quickly succumb to
      infection with normally nonpathogenic Escherichia coli. The susceptible phenotype
      exhibited by Gmm(Apo) adults can be reversed when they receive hemocytes
      transplanted from wild-type donor flies prior to infection. Furthermore, the
      process of immune system development can be restored in intrauterine Gmm(Apo)
      larvae when their mothers are fed a diet supplemented with Wigglesworthia cell
      extracts. Our finding that molecular components of Wigglesworthia exhibit
      immunostimulatory activity within tsetse is representative of a novel
      evolutionary adaptation that steadfastly links an obligate symbiont with its
      host.

PMID- 22368279
TI  - ITAM-coupled receptors inhibit IFNAR signaling and alter macrophage responses to
      TLR4 and Listeria monocytogenes.
AB  - ITAM-coupled receptors play an essential role in regulating macrophage activation
      and function by cross-regulating signaling from heterologous receptors. We
      investigated mechanisms by which ITAM-associated receptors inhibit type I IFN
      (IFN-alpha/beta) signaling in primary human macrophages and tested the effects of
      simultaneous ligation of ITAM-associated receptors and TLR4 on TLR4-induced Jak
      STAT signaling that is mediated by autocrine IFN-beta. Preligation of ITAM
      coupled beta2 integrins and FcgammaRs inhibited proximal signaling by the type I
      IFN receptor IFNAR. Cross-inhibition of IFNAR signaling by beta2 integrins
      resulted in decreased Jak1 activation and was mediated by partial downregulation
      of the IFNAR1 subunit and MAPK-dependent induction of USP18, which blocks the
      association of Jak1 with IFNAR2. Simultaneous engagement of ITAM-coupled beta2
      integrins or Dectin-1 with TLR4 did not affect TLR4-induced direct activation of
      inflammatory target genes such as TNF or IL6 but abrogated subsequent induction
      of IFN response genes that is mediated by autocrine IFN-beta signaling. Type I
      IFNs promote macrophage death postinfection by Listeria monocytogenes.
      Consequently, attenuation of IFN responses by beta2 integrins protected primary
      human macrophages from L. monocytogenes-induced apoptosis. These results provide
      a mechanism for cross-inhibition of type I IFN signaling by ITAM-coupled beta2
      integrins and demonstrate that ITAM signaling qualitatively modulates macrophage
      responses to pathogen-associated molecular patterns and pathogens by selectively
      suppressing IFN responses.

PMID- 22368280
TI  - Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally
      similar to myeloid-derived suppressor cells during SIV and HIV infection.
AB  - Monocytes have been categorized in three main subpopulations based on CD14 and
      CD16 surface expression. Classical monocytes express the CD14(++)CD16(-)CCR2(+)
      phenotype and migrate to inflammatory sites by quickly responding to CCL2
      signaling. Here, we identified and characterized the expansion of a novel
      monocyte subset during HIV and SIV infection, which were undistinguishable from
      classical monocytes, based on CD14 and CD16 expression, but expressed
      significantly lower surface CCR2. Transcriptome analysis of sorted cells
      demonstrated that the CCR2(low/neg) cells are a distinct subpopulation and
      express lower levels of inflammatory cytokines and activation markers than their
      CCR2(high) counterparts. They exhibited impaired phagocytosis and greatly
      diminished chemotaxis in response to CCL2 and CCL7. In addition, these monocytes
      are refractory to SIV infection and suppress CD8(+) T cell proliferation in
      vitro. These cells express higher levels of STAT3 and NOS2, suggesting a
      phenotype similar to monocytic myeloid-derived cells, which suppress expansion of
      CD8(+) T cells in vivo. They may reflect an antiproliferative response against
      the extreme immune activation observed during HIV and SIV infections. In
      addition, they may suppress antiviral responses and thus, have a role in AIDS
      pathogenesis. Antiretroviral therapy in infected macaque and human subjects
      caused this population to decline, suggesting that this atypical phenotype is
      linked to viral replication.

PMID- 22368283
TI  - Human PIH1 associates with histone H4 to mediate the glucose-dependent
      enhancement of pre-rRNA synthesis.
AB  - Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the
      synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here,
      we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly
      with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA
      genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive
      chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the
      occupancy of not only the Brg1 complex but also the Pol I complex at the core
      promoter and enhances transcription initiation of rRNA genes. Additionally, the
      interaction between PIH1 and H4K16 expels TIP5, a component of the silencing
      nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1
      is involved in the derepression of NoRC-silenced rRNA genes. These data indicate
      that PIH1 is a positive regulator of human rRNA genes and is of great importance
      for the recovery of human cells from nutrient starvation and the transition to
      glucose-induced exponential growth in vivo.

PMID- 22368282
TI  - Analysis of Delta12-fatty acid desaturase function revealed that two distinct
      pathways are active for the synthesis of PUFAs in T. aureum ATCC 34304.
AB  - Thraustochytrids are known to synthesize PUFAs such as docosahexaenoic acid
      (DHA). Accumulating evidence suggests the presence of two synthetic pathways of
      PUFAs in thraustochytrids: the polyketide synthase-like (PUFA synthase) and
      desaturase/elongase (standard) pathways. It remains unclear whether the latter
      pathway functions in thraustochytrids. In this study, we report that the standard
      pathway produces PUFA in Thraustochytrium aureum ATCC 34304. We isolated a gene
      encoding a putative Delta12-fatty acid desaturase (TauDelta12des) from T. aureum.
      Yeasts transformed with the tauDelta12des converted endogenous oleic acid (OA)
      into linoleic acid (LA). The disruption of the tauDelta12des in T. aureum by
      homologous recombination resulted in the accumulation of OA and a decrease in the
      levels of LA and its downstream PUFAs. However, the DHA content was increased
      slightly in tauDelta12des-disruption mutants, suggesting that DHA is primarily
      produced in T. aureum via the PUFA synthase pathway. The transformation of the
      tauDelta12des-disruption mutants with a tauDelta12des expression cassette
      restored the wild-type fatty acid profiles. These data clearly indicate that
      TauDelta12des functions as Delta12-fatty acid desaturase in the standard pathway
      of T. aureum and demonstrate that this thraustochytrid produces PUFAs via both
      the PUFA synthase and the standard pathways.

PMID- 22368281
TI  - Genome-wide association study of genetic determinants of LDL-c response to
      atorvastatin therapy: importance of Lp(a).
AB  - We carried out a genome-wide association study (GWAS) of LDL-c response to statin
      using data from participants in the Collaborative Atorvastatin Diabetes Study
      (CARDS; n = 1,156), the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n =
      895), and the observational phase of ASCOT (n = 651), all of whom were prescribed
      atorvastatin 10 mg. Following genome-wide imputation, we combined data from the
      three studies in a meta-analysis. We found associations of LDL-c response to
      atorvastatin that reached genome-wide significance at rs10455872 (P = 6.13 * 10(
      9)) within the LPA gene and at two single nucleotide polymorphisms (SNP) within
      the APOE region (rs445925; P = 2.22 * 10(-16) and rs4420638; P = 1.01 * 10(-11))
      that are proxies for the epsilon2 and epsilon4 variants, respectively, in APOE.
      The novel association with the LPA SNP was replicated in the PROspective Study of
      Pravastatin in the Elderly at Risk (PROSPER) trial (P = 0.009). Using CARDS data,
      we further showed that atorvastatin therapy did not alter lipoprotein(a) [Lp(a)]
      and that Lp(a) levels accounted for all of the associations of SNPs in the LPA
      gene and the apparent LDL-c response levels. However, statin therapy had a
      similar effect in reducing cardiovascular disease (CVD) in patients in the top
      quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower
      three quartiles (HR = 0.66; P = 0.8 for interaction). The data emphasize that
      high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of
      LDL-c response. Therefore, an apparently lower LDL-c response to statin therapy
      may indicate a need for measurement of Lp(a). However, statin therapy seems
      beneficial even in those with high Lp(a).

PMID- 22368285
TI  - Endometriosis is associated with an increased risk of ovarian cancer, study
      shows.

PMID- 22368284
TI  - A sore red eye with systemic involvement.

PMID- 22368286
TI  - Paediatricians call for government to withdraw the health bill.

PMID- 22368287
TI  - Government wins vote to keep risk assessment of NHS reforms private.

PMID- 22368288
TI  - Government must do more to de-politicise science, says US group.

PMID- 22368289
TI  - Information failings at Scottish health authority led to inaction on adverse
      clinical events.

PMID- 22368290
TI  - Head of healthcare watchdog resigns after series of damming reports.

PMID- 22368291
TI  - Medical ethics conference hears about professional responsibility, patient
      autonomy, and corporate power.

PMID- 22368292
TI  - Prices for NHS services can change by 10% every year, finds study.

PMID- 22368293
TI  - Diagnosis of Helicobacter pylori infection.

PMID- 22368294
TI  - Public health director says he has been bullied for criticising health bill.

PMID- 22368295
TI  - Banning "below cost" alcohol will have little effect on consumption, say
      researchers.

PMID- 22368296
TI  - Decreased prevalence of diabetes in marijuana users: cross-sectional data from
      the National Health and Nutrition Examination Survey (NHANES) III.
AB  - OBJECTIVE: To determine the association between diabetes mellitus (DM) and
      marijuana use. DESIGN: Cross-sectional study. SETTING: Data from the National
      Health and Nutrition Examination Survey (NHANES III, 1988-1994) conducted by the
      National Center for Health Statistics of the Centers for Disease Control and
      Prevention. PARTICIPANTS: The study included participants of the NHANES III, a
      nationally representative sample of the US population. The total analytic sample
      was 10 896 adults. The study included four groups (n=10 896): non-marijuana users
      (61.0%), past marijuana users (30.7%), light (one to four times/month) (5.0%) and
      heavy (more than five times/month) current marijuana users (3.3%). DM was defined
      based on self-report or abnormal glycaemic parameters. We analysed data related
      to demographics, body mass index, smoking status, alcohol use, total serum
      cholesterol, high-density lipoprotein, triglyceride, serum 25-hydroxy vitamin D,
      plasma haemoglobin A1c, fasting plasma glucose level and the serum levels of C
      reactive protein and four additional inflammatory markers as related to marijuana
      use. MAIN OUTCOME MEASURES: OR for DM associated with marijuana use adjusted for
      potential confounding variables (ie, odds of DM in marijuana users compared with
      non-marijuana users). RESULTS: Marijuana users had a lower age-adjusted
      prevalence of DM compared to non-marijuana users (OR 0.42, 95% CI 0.33 to 0.55;
      p<0.0001). The prevalence of elevated C reactive protein (>0.5 mg/dl) was
      significantly higher (p<0.0001) among non-marijuana users (18.9%) than among past
      (12.7%) or current light (15.8%) or heavy (9.2%) users. In a robust multivariate
      model controlling for socio-demographic factors, laboratory values and
      comorbidity, the lower odds of DM among marijuana users was significant (adjusted
      OR 0.36, 95% CI 0.24 to 0.55; p<0.0001). CONCLUSIONS: Marijuana use was
      independently associated with a lower prevalence of DM. Further studies are
      needed to show a direct effect of marijuana on DM.

PMID- 22368297
TI  - Quality of medical care and excess mortality in psychiatric patients--a
      nationwide register-based study in Sweden.
AB  - OBJECTIVE: To assess overall and cause-specific mortality and the quality of
      somatic care among psychiatric patients. DESIGN: A register-based cohort study.
      SETTING: All individuals aged 20-79 years in Sweden in 2005. PARTICIPANTS: In
      total 6 294 339 individuals. PRIMARY OUTCOME MEASURE: The individuals were
      followed for mortality in 2006 and 2007, generating 72 187 deaths. Psychiatric
      patients were grouped according to their diagnosis in the National Patient
      Register. Mortality risk of psychiatric patients was compared with that of non
      psychiatric patients. Estimates of RR of mortality were calculated as incidence
      rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Psychiatric
      patients were compared with non-psychiatric patients for three healthcare quality
      indicators: the proportion of avoidable hospitalisations, case death rate after
      myocardial infarction and statin use among diabetic patients. RESULTS: Compared
      with individuals with no episodes of treatment for mental disorder, psychiatric
      patients had a substantially increased risk of all studied causes of death as
      well as death from conditions considered amenable to intervention by the health
      service, that is, avoidable mortality. The highest mortality was found among
      those with another mental disorder, predominantly substance abuse (for women, an
      IRR of 4.7 (95% CI 4.3 to 5.0) and for men, an IRR of 4.8 (95% CI 4.6 to 5.0)).
      The analysis of quality of somatic care revealed lower levels of healthcare
      quality for psychiatric patients, signalling failures in public health and
      medical care. CONCLUSION: This study shows a marked increase in excess mortality,
      suggesting a lower quality of somatic healthcare in psychiatric patients.

PMID- 22368298
TI  - Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch
      repair (MMR) gene mutation status: a literature review assessing utility of
      tumour features for MMR variant classification.
AB  - Colorectal cancer (CRC) that demonstrates microsatellite instability (MSI) is
      caused by either germline mismatch repair (MMR) gene mutations, or 'sporadic'
      somatic tumour MLH1 promoter methylation. MLH1 promoter methylation is reportedly
      correlated with tumour BRAF V600E mutation status. No systematic review has been
      undertaken to assess the value of BRAF V600E mutation and MLH1 promoter
      methylation tumour markers as negative predictors of germline MMR mutation
      status. A literature review of CRC cohorts tested for MMR mutations, and tumour
      BRAF V600E mutation and/or MLH1 promoter methylation was conducted using PubMed.
      Studies were assessed for tumour features, stratified by tumour MMR status based
      on immunohistochemistry or MSI where possible. Pooled frequencies and 95% CIs
      were calculated using a random effects model. BRAF V600E results for 4562 tumours
      from 35 studies, and MLH1 promoter methylation results for 2975 tumours from 43
      studies, were assessed. In 550 MMR mutation carriers, the BRAF V600E mutation
      frequency was 1.40% (95% CI 0.06% to 3%). In MMR mutation-negative cases, the
      BRAF V600E mutation frequency was 5.00% (95% CI 4% to 7%) in 1623 microsatellite
      stable (MSS) cases and 63.50% (95% CI 47% to 79%) in 332 cases demonstrating MLH1
      methylation or MLH1 expression loss. MLH1 promoter methylation of the 'A region'
      was reported more frequently than the 'C region' in MSS CRCs (17% vs 0.06%,
      p<0.0001) and in MLH1 mutation carriers (42% vs 6%, p<0.0001), but not in MMR
      mutation-negative MSI-H CRCs (40% vs 47%, p=0.12). Methylation of the 'C region'
      was a predictor of MMR mutation-negative status in MSI-H CRC cases (47% vs 6% in
      MLH1 mutation carriers, p<0.0001). This review demonstrates that tumour BRAF
      V600E mutation, and MLH1 promoter 'C region' methylation specifically, are strong
      predictors of negative MMR mutation status. It is important to incorporate these
      features in multifactorial models aimed at predicting MMR mutation status.

PMID- 22368299
TI  - CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.
AB  - Background Most familial pancreatic cancer (FPC) remains unexplained. The
      identification of individuals with a high genetic risk of developing pancreatic
      adenocarcinoma (PC) is important to elucidate its biological basis and is
      critical to better define emerging strategies for the detection of early
      pancreatic neoplasms.  Patients and methods A series of 225 consecutively
      enrolled patients with PC were tested for CDKN2A mutations. After personal and
      family cancer histories of all the patients had been reviewed, a subset of the
      patients were classified as FPC and were also tested for mutations in PALLD,
      PALB2, BRCA1 and BRCA2 as FPC candidate genes.  Results The CDKN2A mutation rate
      in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W,
      were predominant, but the mutation spectrum also included p.L65P, p.G67R and two
      novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and
      p.R144C. None of the patients with FPC harboured germline mutations in PALLD,
      PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L.
      Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. 
      Conclusion These findings suggest that a sizeable subset of Italian FPC families
      may carry CDKN2A mutations. This result may be of value for identifying the best
      candidates for future PC screening trials in Italy.

PMID- 22368300
TI  - Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration
      defects.
AB  - BACKGROUND: DYNC1H1 encodes the heavy chain protein of the cytoplasmic dynein 1
      motor protein complex that plays a key role in retrograde axonal transport in
      neurons. Furthermore, it interacts with the LIS1 gene of which haploinsufficiency
      causes a severe neuronal migration disorder in humans, known as classical
      lissencephaly or Miller-Dieker syndrome. AIM: To describe the clinical spectrum
      and molecular characteristics of DYNC1H1 mutations. METHODS: A family based exome
      sequencing approach was used to identify de novo mutations in patients with
      severe intellectual disability. RESULTS: In this report the identification of two
      de novo missense mutations in DYNC1H1 (p.Glu1518Lys and p.His3822Pro) in two
      patients with severe intellectual disability and variable neuronal migration
      defects is described. CONCLUSION: Since an autosomal dominant mutation in DYNC1H1
      was previously identified in a family with the axonal (type 2) form of Charcot-
      Marie-Tooth (CMT2) disease and mutations in Dync1h1 in mice also cause impaired
      neuronal migration in addition to neuropathy, these data together suggest that
      mutations in DYNC1H1 can lead to a broad phenotypic spectrum and confirm the
      importance of DYNC1H1 in both central and peripheral neuronal functions.

PMID- 22368301
TI  - Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency.
AB  - BACKGROUND: COQ4 encodes a protein that organises the multienzyme complex for the
      synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13
      was identified in a 3-year-old boy with mental retardation, encephalomyopathy and
      dysmorphic features. Because the deletion encompassed COQ4, the patient was
      screened for CoQ(10) deficiency. METHODS: A complete molecular and biochemical
      characterisation of the patient's fibroblasts and of a yeast model were
      performed. RESULTS: The study found reduced COQ4 expression (48% of controls),
      CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities
      of respiratory chain complex II+III. Cells displayed a growth defect that was
      corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in
      HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeast
      haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of
      other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency,
      underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in
      a significant improvement of neuromuscular symptoms, which reappeared after
      supplementation was temporarily discontinued. CONCLUSION: Mutations of COQ4
      should be searched for in patients with CoQ(10) deficiency and encephalomyopathy;
      patients with genomic rearrangements involving COQ4 should be screened for
      CoQ(10) deficiency, as they could benefit from supplementation.

PMID- 22368302
TI  - Single nucleotide polymorphisms in the NOS2 and NOS3 genes are associated with
      exhaled nitric oxide.
AB  - BACKGROUND: Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3)
      have been suggested to have a major impact on fraction of exhaled nitric oxide
      (FENO), a biomarker of airway inflammation. However, the genetic contribution of
      NOS polymorphisms to FENO is not fully understood. The aim of this study was to
      investigate comprehensively the association between single nucleotide
      polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and
      to assess whether such associations are modified by asthma or atopy. METHOD: In
      1737 adults from a Swedish general population sample, FENO was measured and
      genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect
      of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple
      regression methods. RESULTS: In a multi-SNP model based on stepwise regression
      analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with
      levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%)
      higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT
      genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For
      NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher
      levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%,
      95% CI 4.6% to 42.0%). CONCLUSION: These results suggest that NOS2 is the major
      NOS gene determining variability in exhaled nitric oxide in the healthy adult
      population, while NOS3 may play a more important role in asthmatic adults.

PMID- 22368303
TI  - Who Expressed What Emotion? Men Grab Anger, Women Grab Happiness.
AB  - When anger or happiness flashes on a face in the crowd, do we misperceive that
      emotion as belonging to someone else? Two studies found that misperception of
      apparent emotional expressions - "illusory conjunctions" - depended on the gender
      of the target: male faces tended to "grab" anger from neighboring faces, and
      female faces tended to grab happiness. Importantly, the evidence did not suggest
      that this effect was due to the general tendency to misperceive male or female
      faces as angry or happy, but instead indicated a more subtle interaction of
      expectations and early visual processes. This suggests a novel aspect of
      affordance-management in human perception, whereby cues to threat, when they
      appear, are attributed to those with the greatest capability of doing harm,
      whereas cues to friendship are attributed to those with the greatest likelihood
      of providing affiliation opportunities.

PMID- 22368305
TI  - One-pot Double Suzuki Couplings of Dichloropyrimidines.
AB  - An effective one-pot, regioselective double Suzuki coupling of 2,4
      dichloropyrimidine has been developed, which enables the quick and efficient
      synthesis of diarylated pyrimidines. The choice of solvent proved critical to the
      success of this reaction sequence, with alcoholic solvent mixtures affording much
      greater reactivity and correspondingly lower temperatures than the use of polar
      aprotic solvents.

PMID- 22368304
TI  - Mixture modelling as an exploratory framework for genotype-trait associations.
AB  - We propose a mixture modelling framework for both identifying and exploring the
      nature of genotype-trait associations. This framework extends the classical mixed
      effects modelling approach for this setting by incorporating a Gaussian mixture
      distribution for random genotype effects. The primary advantages of this paradigm
      over existing approaches include that the mixture modelling framework addresses
      the degrees-of-freedom challenge that is inherent in application of the usual
      fixed effects analysis of covariance, relaxes the restrictive single normal
      distribution assumption of the classical mixed effects models and offers an
      exploratory framework for discovery of underlying structure across multiple
      genetic loci. An application to data arising from a study of antiretroviral
      associated dyslipidaemia in human immunodeficiency virus infection is presented.
      Extensive simulations studies are also implemented to investigate the performance
      of this approach.

PMID- 22368306
TI  - Fast dye salts provide fast access to azidoarene synthons in multi-step one-pot
      tandem click transformations.
AB  - This study examined whether commercially available diazonium salts could be used
      as efficient aromatic azide precursors in one-pot multi-step click
      transformations. Seven different diazonium salts, including Fast Red RC, Fast
      Blue B, Fast Corinth V and Variamine Blue B were surveyed under aqueous click
      reaction conditions of CuSO(4)/Na ascorbate catalyst with 1:1 t-BuOH:H(2)O
      solvent. Two-step tandem reactions with terminal alkyne and diyne co-reactants
      led to 1,2,3-triazole products in 66%-88% yields, while three-step tandem
      reactions with trimethylsilyl-protected alkyne and diyne co-reactants led to
      1,2,3-triazole products in 61%-78% yields.

PMID- 22368307
TI  - Facile and rapid route for the synthesis of novel conformationally constrained
      norstatine analogs via PADAM-cyclization methodology.
AB  - The following report describes novel methodology for the rapid synthesis of
      unique conformationally constrained norstatine analogs of potential biological
      relevance. A PADAM (Passerini reaction - Amine Deprotection - Acyl Migration
      reaction) sequence is followed by a TFA-mediated microwave-assisted cyclization
      to generate the final benzimidazole isostere of the norstatine scaffold in
      moderate to good yields. The applicability of this solution phase methodology to
      the preparation of a small collection of compounds is discussed.

PMID- 22368308
TI  - A New Class of Minimum Power Divergence Estimators with Applications to Cancer
      Surveillance.
AB  - The Annual Percent Change (APC) has been adopted as a useful measure for
      analyzing the changing trends of cancer mortality and incidence rates by the NCI
      SEER program. Difficulties, however, arise when comparing the sample APCs between
      two overlapping regions because of the induced dependence (e.g., comparing the
      cancer mortality change rate of California with the national level). This paper
      deals with a new perspective of understanding the sample distribution of the test
      statistics for comparing the APCs between overlapping regions. Our proposal
      allows for computational readiness and easy interpretability. We further propose
      a more general family of estimators, namely, the so-called minimum power
      divergence estimators, including the maximum likelihood estimators as a special
      case. Our simulation experiments support the superiority of the proposed
      estimator to the conventional maximum likelihood estimator. The proposed method
      is illustrated by the analysis of the SEER cancer mortality rates observed from
      1991 to 2006.

PMID- 22368309
TI  - Model Selection and Estimation in the Matrix Normal Graphical Model.
AB  - Motivated by analysis of gene expression data measured over different tissues or
      over time, we consider matrix-valued random variable and matrix-normal
      distribution, where the precision matrices have a graphical interpretation for
      genes and tissues, respectively. We present a l(1) penalized likelihood method
      and an efficient coordinate descent-based computational algorithm for model
      selection and estimation in such matrix normal graphical models (MNGMs). We
      provide theoretical results on the asymptotic distributions, the rates of
      convergence of the estimates and the sparsistency, allowing both the numbers of
      genes and tissues to diverge as the sample size goes to infinity. Simulation
      results demonstrate that the MNGMs can lead to better estimate of the precision
      matrices and better identifications of the graph structures than the standard
      Gaussian graphical models. We illustrate the methods with an analysis of mouse
      gene expression data measured over ten different tissues.

PMID- 22368310
TI  - Multiscale analysis of water uptake and erosion in biodegradable polyarylates.
AB  - The role of hydration in degradation and erosion of materials, especially
      biomaterials used in scaffolds and implants, was investigated by studying the
      distribution of water at length scales from 0.1 nm to 0.1 mm using Raman
      spectroscopy, small-angle neutron scattering (SANS), Raman confocal imaging, and
      scanning electron microscopy (SEM). The measurements were demonstrated using L
      tyrosine derived polyarylates. Bound- and free- water were characterized using
      their respective signatures in the Raman spectra. In the presence of deuterium
      oxide (D(2)O), H-D exchange occurred at the amide carbonyl but was not detected
      at the ester carbonyl. Water appeared to be present in the polymer even in
      regions where there was little evidence for N-H to N-D exchange. SANS showed that
      water is not uniformly dispersed in the polymer matrix. The distribution of water
      can be described as mass fractals in polymers with low water content (~5 wt%),
      and surface fractals in polymers with larger water content (15 to 60 wt%). These
      fluctuations in the density of water distribution are presumed to be the
      precursors of the ~ 20 MUm water pockets seen by Raman confocal imaging, and also
      give rise to 10-50 MUm porous network seen in SEM. The surfaces of these polymers
      appeared to resist erosion while the core of the films continued to erode to form
      a porous structure. This could be due to differences in either the density of the
      polymer or the solvent environment in the bulk vs. the surface, or a combination
      of these two factors. There was no correlation between the rate of degradation
      and the amount of water uptake in these polymers, and this suggests that it is
      the bound-water and not the total amount of water that contributes to hydrolytic
      degradation.

PMID- 22368311
TI  - Land-cover classification in a moist tropical region of Brazil with Landsat TM
      imagery.
AB  - This research aims to improve land-cover classification accuracy in a moist
      tropical region in Brazil by examining the use of different remote sensing
      derived variables and classification algorithms. Different scenarios based on
      Landsat Thematic Mapper (TM) spectral data and derived vegetation indices and
      textural images, and different classification algorithms - maximum likelihood
      classification (MLC), artificial neural network (ANN), classification tree
      analysis (CTA), and object-based classification (OBC), were explored. The results
      indicated that a combination of vegetation indices as extra bands into Landsat TM
      multispectral bands did not improve the overall classification performance, but
      the combination of textural images was valuable for improving vegetation
      classification accuracy. In particular, the combination of both vegetation
      indices and textural images into TM multispectral bands improved overall
      classification accuracy by 5.6% and kappa coefficient by 6.25%. Comparison of the
      different classification algorithms indicated that CTA and ANN have poor
      classification performance in this research, but OBC improved primary forest and
      pasture classification accuracies. This research indicates that use of textural
      images or use of OBC are especially valuable for improving the vegetation classes
      such as upland and liana forest classes having complex stand structures and
      having relatively large patch sizes.

PMID- 22368312
TI  - 'Don't Leave Me Hanging': Homeless Mothers' Perceptions of Service Providers.
AB  - Few interventions have been developed for substance-abusing homeless mothers.
      Among those interventions, high dropout rates (up to 85%) are consistently
      reported. Understanding homeless mothers' experiences with service providers may
      be an important first step to understanding ways to increase treatment
      engagement. Therefore, the current study used qualitative methods to gain a
      better understanding of homeless mothers' perceptions of service providers. A
      total of 28 mothers who were currently residing at a homeless shelter in a
      Midwestern city participated in three focus groups. Overall, mothers held
      negative perceptions of service providers related to understanding, support, and
      fear. Based upon this study's findings, recommendations are offered to improve
      service delivery and guide future research.

PMID- 22368313
TI  - "We'll Figure a Way": Teenage Mothers' Experiences in Shifting Social and
      Economic Contexts.
AB  - The current economic and social context calls for a renewed assessment of the
      consequences of an early transition to parenthood. In interviews with 55 teenage
      mothers in Colorado, we find that they are experiencing severe economic and
      social strains. Financially, although most are receiving substantial help from
      family members and sometimes their children's fathers, basic needs often remain
      unmet. Macroeconomic and family structure trends have resulted in deprived
      material circumstances, while welfare reform and other changes have reduced the
      availability of aid. Socially, families' and communities' disapproval of early
      childbearing negatively influences the support young mothers receive, their
      social interactions, and their experiences with social institutions.

PMID- 22368314
TI  - Density Estimation in Several Populations With Uncertain Population Membership.
AB  - We devise methods to estimate probability density functions of several
      populations using observations with uncertain population membership, meaning from
      which population an observation comes is unknown. The probability of an
      observation being sampled from any given population can be calculated. We develop
      general estimation procedures and bandwidth selection methods for our setting. We
      establish large-sample properties and study finite-sample performance using
      simulation studies. We illustrate our methods with data from a nutrition study.

PMID- 22368315
TI  - Scant evidence for Spearman's law of diminishing returns in middle childhood.
AB  - In 1927, Charles Spearman suggested that general cognitive ability, or g, might
      be stronger at the low end of ability. We explored the manifold of g across the
      ability distribution in a large sample (range >800 to >4000 individuals) of
      British twins assessed longitudinally at 7, 9 and 10 years old using two verbal
      and two nonverbal tests at each age, thus testing effects of age on the
      saturation of g. We rankit-normalized the test scores, then used a median split
      on the test with the highest factor-loading. We derived the first principal
      component from the remaining three tests. We performed each analysis for the
      whole sample (within age) and also separately by sex. The first principal
      component explains more variance in g in the low ability group at every age and
      in both sexes separately but the F ratio eigenvalues show that, except at age 7
      and principally in females, the difference between the low and high ability
      groups is not significant.

PMID- 22368316
TI  - HIV-positive Mothers' Communication About Safer Sex And STD Prevention With Their
      Children.
AB  - Mothers play an important role in promoting the sexual health of their adolescent
      children. Fifty-seven HIV-positive mothers with adolescent children participated
      in an in-depth, qualitative interview regarding whether they have talked to their
      children about safer sex and STD prevention, including at what age they began
      such discussions, and what messages they gave to their children. The majority of
      mothers (95%) had talked with their child about safer sex; some began such
      discussions when the children were as young as 6 years old, but most began when
      the children were around 12 years old. Mothers' messages fell into the following
      areas: (1) protecting oneself from STDs; (2) giving factual information regarding
      STDs, including HIV; (3) avoiding pregnancy; (4) empowering and respecting
      oneself; and (5) communicating with sexual partners. The mothers' own HIV status
      impacted the discussions with their children. Content of mothers' messages, child
      reactions, and child outcomes are discussed.

PMID- 22368317
TI  - A novel, implicit treatment for language comprehension processes in right
      hemisphere brain damage: Phase I data.
AB  - BACKGROUND: This manuscript reports the initial phase of testing for a novel,
      "Contextual constraint" treatment, designed to stimulate inefficient language
      comprehension processes in adults with right hemisphere brain damage (RHD). Two
      versions of treatment were developed to target two normal comprehension processes
      that have broad relevance for discourse comprehension and that are often
      disrupted by RHD: coarse semantic coding and suppression. The development of the
      treatment was informed by two well-documented strengths of the RHD population.
      The first is consistently better performance on assessments that are implicit, or
      nearly so, than on explicit, metalinguistic measures of language and cognitive
      processing. The second is improved performance when given linguistic context that
      moderately-to-strongly biases an intended meaning. Treatment consisted of
      providing brief context sentences to prestimulate, or constrain, intended
      interpretations. Participants made no explicit associations or judgments about
      the constraint sentences; rather, these contexts served only as implicit primes. 
      AIMS: This Phase I treatment study aimed to determine the effects of a novel,
      implicit, Contextual Constraint treatment in adults with RHD whose coarse coding
      or suppression processes were inefficient. Treatment was hypothesized to speed
      coarse coding or suppression function in these individuals.  METHODS
      #ENTITYSTARTX00026; PROCEDURES: Three adults with RHD participated in this study,
      one (P1) with a coarse coding deficit and two (P2, P3) with suppression deficits.
      Probe tasks were adapted from prior studies of coarse coding and suppression in
      RHD. The dependent measure was the percentage of responses that met predetermined
      response time criteria. When pre-treatment baseline performance was stable,
      treatment was initiated. There were two levels of contextual constraint, Strong
      and Moderate, and treatment for each item began with the provision of the Strong
      constraint context.  OUTCOMES #ENTITYSTARTX00026; RESULTS: Treatment-contingent
      gains were evident after brief periods of treatment, for P1 on two treatment
      lists, and for P2. P3 made slower but still substantial gains. Maintenance of
      gains was evident for P1, the only participant for whom it was measured. 
      CONCLUSIONS: This Phase I treatment study documents the potential for
      considerable gains from an implicit, Contextual constraint treatment. If
      replicated, this approach to treatment may hold promise for individuals who do
      poorly with effortful, metalinguistic treatment tasks, or for whom it is
      desirable to minimize errors during treatment. The real test of this treatment's
      benefit will come from later phase studies of study, which will test broad-based
      generalization to various aspects of discourse comprehension.

PMID- 22368319
TI  - ?
AB  - To theoretically compare the behavior of different algorithms, compatible
      performance measures are necessary. Thus in the first part, an analysis approach,
      developed for evolution strategies, was applied to simultaneous perturbation
      stochastic approximation on the noisy sphere model. A considerable advantage of
      this approach is that convergence results for non-noisy and noisy optimization
      can be obtained simultaneously. Next to the convergence rates, optimal step sizes
      and convergence criteria for 3 different noise models were derived. These results
      were validated by simulation experiments. Afterward, the results were used for a
      comparison with evolution strategies on the sphere model in combination with the
      3 noise models. It was shown that both strategies perform similarly, with a
      slight advantage for SPSA if optimal settings are used and the noise strength is
      not too large.

PMID- 22368318
TI  - Scope and Mechanistic Study of the Coupling Reaction of alpha, beta-Unsaturated
      Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene
      Insertion vs Oxidative Coupling Pathways.
AB  - The cationic ruthenium-hydride complex [(C(6)H(6))(PCy(3))(CO)RuH](+)BF(4) (-)
      (1) was found to be a highly effective catalyst for the intermolecular conjugate
      addition of simple alkenes to alpha,beta-unsaturated carbonyl compounds to give
      (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction
      of cinnamides with electron-deficient olefins led to the oxidative coupling of
      two olefinic C-H bonds in forming (E)-selective diene products. The
      intramolecular version of the coupling reaction efficiently produced indene and
      bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of
      ethyl cinnamate with propene was determined as: rate =
      k[1](1)[propene](0)[cinnamate](-1). A negligible deuterium kinetic isotope effect
      (k(H)/k(D) = 1.1+/-0.1) was measured from both (E)-C(6)H(5)CH=C(CH(3))CONHCH(3)
      and (E)-C(6)H(5)CD=C(CH(3))CONHCH(3) with styrene. In contrast, a significant
      normal isotope effect (k(H)/k(D) = 1.7+/-0.1) was observed from the reaction of
      (E)-C(6)H(5)CH=C(CH(3))CONHCH(3) with styrene and styrene-d(10). A pronounced
      carbon isotope effect was measured from the coupling reaction of (E)
      C(6)H(5)CH=CHCO(2)Et with propene ((13)C(recovered)/(13)C(virgin) at C(beta) =
      1.019(6)), while a negligible carbon isotope effect
      ((13)C(recovered)/(13)C(virgin) at C(beta) = 0.999(4)) was obtained from the
      reaction of (E)-C(6)H(5)CH=C(CH(3))CONHCH(3) with styrene. Hammett plots from the
      correlation of para-substituted p-X-C(6)H(4)CH=CHCO(2)Et (X = OCH(3), CH(3), H,
      F, Cl, CO(2)Me, CF(3)) with propene and from the treatment of (E)
      C(6)H(5)CH=CHCO(2)Et with a series of para-substituted styrenes p-Y
      C(6)H(4)CH=CH(2) (Y = OCH(3), CH(3), H, F, Cl, CF(3)) gave the positive slopes
      for both cases (rho = +1.1+/-0.1 and +1.5+/-0.1, respectively). Eyring analysis
      of the coupling reaction led to the thermodynamic parameters, Delta H(?) = 20+/-2
      kcal mol(-1) and S(?) = -42+/-5 e.u. Two separate mechanistic pathways for the
      coupling reaction have been proposed on the basis of these kinetic and
      spectroscopic studies.

PMID- 22368320
TI  - ?
AB  - A simple approximation within the framework of the hybrid methods for the
      calculation of the electronic structure of solids is presented. By considering
      only the diagonal elements of the matrix of the perturbation operator (Hartree
      Fock exchange minus semilocal exchange) calculated in the basis of the semilocal
      orbitals, the computational time is drastically reduced, while keeping very well
      in most studied cases the accuracy of the results obtained with hybrid
      functionals when applied without any approximations.

PMID- 22368321
TI  - ?
AB  - A comprehensive study concerning the reproducibility and stability of organic n
      type field effect transistors is presented. C(60) based OFETs were chosen to
      investigate the fabrication reproducibility and the long term stability because
      C(60) is a high mobility n-type material. We fabricated 48 transistors and each
      transistor was measured for 24 h inside the glove box. To test for life time
      stability - long term measurements up to three months have been undertaken. We
      report about the fluctuations in the device parameters of all investigated
      transistors by comparing the transfer characteristics, and on/off ratio for short
      time and long time measurements. C(60) based OFETs showed good reproducibility
      and stability for short time measurements and a decay for long time measurements.

PMID- 22368322
TI  - Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and
      their Role in Disorders like Developmental Dyscalculia.
AB  - The aim of this article is to report on the importance and challenges of a time
      resolved and spatio-temporal analysis of fMRI data from complex cognitive
      processes and associated disorders using a study on developmental dyscalculia
      (DD). Participants underwent fMRI while judging the incorrectness of
      multiplication results, and the data were analyzed using a sequence of methods,
      each of which progressively provided more a detailed picture of the spatio
      temporal aspect of this disease. Healthy subjects and subjects with DD performed
      alike behaviorally though they exhibited parietal disparities using traditional
      voxel-based group analyses. Further and more detailed differences, however,
      surfaced with a time-resolved examination of the neural responses during the
      experiment. While performing inter-group comparisons, a third group of subjects
      with dyslexia (DL) but with no arithmetic difficulties was included to test the
      specificity of the analysis and strengthen the statistical base with overall
      fifty-eight subjects. Surprisingly, the analysis showed a functional
      dissimilarity during an initial reading phase for the group of dyslexic but
      otherwise normal subjects, with respect to controls, even though only numerical
      digits and no alphabetic characters were presented. Thus our results suggest that
      time-resolved multi-variate analysis of complex experimental paradigms has the
      ability to yield powerful new clinical insights about abnormal brain function.
      Similarly, a detailed compilation of aberrations in the functional cascade may
      have much greater potential to delineate the core processing problems in mental
      disorders.

PMID- 22368323
TI  - A VOLTAMMETRIC FLAVIN MICROELECTRODE FOR USE IN BIOFILMS.
AB  - Biofilms used in bioelectrochemical systems are expected to transfer electrons
      using electron transfer mediators. One mediator type, flavins, which includes
      flavin mononucleotide, riboflavin, and flavin adenine dinucleotide, has been
      found to be endogenously produced by Shewanella oneidensis MR-1. However, the
      presence and concentration of flavins inside a S. oneidensis MR-1 biofilm have
      never been reported. The goal of this study was to develop a flavin
      microelectrode capable of measuring flavins inside a living biofilm and apply it
      to a biofilm which produces flavins. Because flavins are electrochemically active
      molecules, the flavin microelectrode was based on detection via square-wave
      voltammetry. The microelectrode consisted of a carbon working electrode with a 10
      30 MUm tip diameter, a built-in platinum counter electrode, and a Ag/AgCl
      reference electrode, all enclosed in a glass outer case. The microelectrode was
      calibrated between 0.1 MUM and 10 MUM flavins and showed a linear correlation
      between flavin concentration and peak currents located at -424 mV(Ag/AgCl) on a
      square-wave voltammogram. We also developed a model to explain the
      electrochemical mechanism of flavin detection, and to determine the effective
      surface area of the microelectrode, the standard reduction potential, and the
      transfer coefficient. We found that the effective surface area of the
      microelectrode was close to 100 times the projected surface area. The model
      predicted a standard reduction potential for RF/RFH2 of -419 mV(Ag/AgCl) at 20 
      degrees C and a transfer coefficient of 0.45. Lastly, we measured flavin
      concentration inside a S. oneidensis MR-1 biofilm grown on a glass surface using
      oxygen as the electron acceptor. The flavin concentration reached 0.7 MUM,
      increasing near the bottom of the biofilm, where no oxygen was present. This
      shows the possibility that flavins are produced in the anaerobic zone to act as
      intermediate electron acceptors in the deeper parts of the biofilm, where there
      is no oxygen.

PMID- 22368325
TI  - Winds of change.

PMID- 22368324
TI  - The Cost of Uncertain Life Span.
AB  - A considerable amount of uncertainty surrounds the length of human life. The
      standard deviation in adult life span is about 15 years in the U.S., and theory
      and evidence suggest it is costly. I calibrate a utility-theoretic model of
      preferences over length of life and show that one fewer year in standard
      deviation is worth about half a mean life year. Differences in the standard
      deviation exacerbate cross-sectional differences in life expectancy between the
      U.S. and other industrialized countries, between rich and poor countries, and
      among poor countries. Accounting for the cost of life-span variance also appears
      to amplify recently discovered patterns of convergence in world average human
      well-being. This is partly for methodological reasons and partly because
      unconditional variance in human length of life, primarily the component due to
      infant mortality, has exhibited even more convergence than life expectancy.

PMID- 22368326
TI  - A great loss.

PMID- 22368327
TI  - Research methodology in Dentistry: Part I - The essentials and relevance of
      research.
AB  - The need for scientific evidence should be the basis of clinical practice. The
      field of restorative dentistry and endodontics is evolving at a rapid pace, with
      the introduction of several materials, instruments, and equipments. However,
      there is minimal information of their relevance in clinical practice. On the one
      hand, material and laboratory research is critical, however; its translation into
      clinical practice is not being substantiated enough with clinical research. This
      four part review series focuses on methods to improve evidence-based practice, by
      improving methods to integrate laboratory and clinical research.

PMID- 22368328
TI  - Biologic width and its importance in periodontal and restorative dentistry.
AB  - An adequate understanding of the relationship between periodontal tissues and
      restorative dentistry is paramount to ensure adequate form, function, esthetics
      and comfort of the dentition. While most clinicians are aware of this important
      relationship, uncertainty remains regarding specific concepts such as biologic
      width, its maintenance and applications of crown lengthening in cases of biologic
      width violation. Relevant publications regarding biologic width, its violation
      and management were identified up to August 2011 using manual and electronic
      database search in Medline, Embase, Directory of Open Access Journals and Google
      Scholar. This review discusses the concept of biologic width around tooth and its
      relationship to periodontal health and restorative dentistry.

PMID- 22368329
TI  - An in vitro comparative evaluation of depth of tubular penetration of three resin
      based root canal sealers.
AB  - OBJECTIVE: To evaluate the depth of penetration of three resin-based root canal
      sealers into the dentinal tubules at the cervical, middle and apical third of the
      root canal. MATERIALS AND METHODS: Root canals of 32 extracted human mandibular
      premolar teeth were prepared and obturated using EndoREZ + resin-coated gutta
      percha points (group A), Epiphany + Resilon points (group B), or AH Plus + gutta
      percha (group C). The teeth were split longitudinally in bucco-lingual direction
      and viewed under scanning electron microscope. Photographs were taken at
      cervical, middle and apical levels for all samples and corresponding measurements
      were made. The data obtained was statistically analyzed using one-way ANOVA and
      the post-hoc Bonferroni test for inter-group comparison. RESULTS: The results
      showed that the greatest penetration into dentinal tubules was by EndoREZ sealer
      (525.2 MU, 327.802 MU and 198.36 MU at cervical, middle and apical third),
      followed by Epiphany sealer (479.7 MU, 297.212 MU, and 182.22 MU), and the least
      penetration was seen with AH Plus sealer (224.2 MU, 65.419 MU, and 40.7 MU). The
      penetration of sealer into the dentinal tubules was statistically significant
      between each group at each level and between different levels within each group
      (P<.05). CONCLUSION: The penetration depth of EndoREZ and Epiphany into the
      dentinal tubules is significantly greater than that of AH Plus.

PMID- 22368330
TI  - Antimicrobial effect of chlorhexidine digluconate in dentin: In vitro and in situ
      study.
AB  - AIM: The aim of this study was to evaluate a very short-term in vitro and in situ
      effect of 2% chlorhexidine-digluconate-based (CHX) cavity cleanser on the
      disinfection of dentin demineralized by cariogenic bacteria. MATERIALS AND
      METHODS: Human dentin slabs were randomly allocated and used in 2 distinct
      phases, in vitro and in situ, for obtaining demineralized dentin. In vitro, the
      slabs (n=15) were immersed for 5 days in BHI broth inoculated with Streptococcus
      mutans CTT 3440. In situ, a double-blind design was conducted in one phase of 14
      days, during which 20 volunteers wore palatal devices containing two human dental
      dentin slabs. On 5(th) day in vitro and 14(th) day in situ, the slabs were
      allocated to the two groups: Control group (5 MUl of 0.9% NaCl solution) and CHX
      group (5 MUl of 2% chlorhexidine digluconate solution, Cavity CleanserTM BISCO,
      Schaumburg, IL, EUA), for 5 minutes. The microbiological analyses were performed
      immediately before and after the treatments. RESULTS: The log reductions means
      found for CHX treatment on tested micro organisms were higher when compared to
      Control group either in vitro or in situ conditions. CONCLUSIONS: Our results
      showed that CHX was effective in reducing the cultivable microbiota in
      contaminated dentin. Furthermore, although the use of chlorhexidine-digluconate
      based cavity disinfectant did not completely eliminate the viable microorganisms,
      it served as a suitable agent to disinfect tooth preparations.

PMID- 22368331
TI  - Shear bond strength evaluation of resin composite bonded to glass-ionomer cement
      using self-etching bonding agents with different pH: In vitro study.
AB  - AIM: To evaluate the bonding ability of composite to unset glass-ionomer cement
      (GIC) using different self-etching bonding systems. MATERIALS AND METHODS: One
      hundred samples of composite bonded to unset GIC were prepared and were divided
      into four groups. In Group A, composite was bonded to unset GIC employing a
      strong (pH 1) self-etch primer was used. In Group B, intermediary strong (pH 1.4)
      self-etch primer was employed. In Group C and D, mild (pH 2) and (pH 2.2) self
      etch primer was employed. Shear bond strength analysis was performed at a cross
      head speed of 0.5 mm/min. RESULTS: Statistical analysis performed with one way
      analysis of variance and Tukey's test showed that the bond strength of composite
      to unset GIC was significantly higher for the mild self-etch primer group. In
      addition, energy dispersive x-ray (EDX) analysis was used to determine the
      composition of various structural phases identified by FE-SEM along the GIC
      bonding agent interfaces. CONCLUSION: Hence this present study concludes that
      clinically the use of mild self-etching bonding agent over unset GIC has improved
      bond strength compared to the use of strong and intermediate self-etching bonding
      agent.

PMID- 22368332
TI  - Comparative evaluation of apical extrusion of bacteria using hand and rotary
      systems : An in vitro study.
AB  - AIM: To evaluate the bacteria extruded apically during root canal preparation
      using two hand and rotary instrumentation techniques. MATERIALS AND METHODS:
      Eighty freshly extracted mandibular premolars were mounted in bacteria collection
      apparatus. Root canals were contaminated with the pure culture of Enterococcus
      fecalis (ATCC 29212) and dried at 37 degrees C for 24 h. Bacteria extruded were
      collected, incubated in brain heart infusion agar for 24 h at 36 degrees C and
      the colony forming units (CFU) were counted. STATISTICAL ANALYSIS: The mean
      number of colony forming units were calculated by One-way ANOVA and comparison
      between the groups made by multiple comparison (Dunnet D) test. RESULTS: The step
      back technique extruded highest number of bacteria in comparison to other hand
      and rotary Ni-Ti systems. CONCLUSION: Under the limitation of this study all hand
      and rotary instrumentation techniques extruded bacteria. Among all the
      instrumentation techniques step-back technique extruded more number of bacteria
      and K-3 system the least. Further in vivo research in this direction could
      provide more insight into the biologic factors associated and focus on bacterial
      species that essentially play a major role in post instrumentation flare-ups.

PMID- 22368333
TI  - Comparative evaluation of sealing properties of different obturation systems
      placed over apically fractured rotary NiTi files.
AB  - AIM: To evaluate sealing properties of different obturation systems placed over
      apically fractured rotary NiTi files. MATERIALS AND METHODS: Forty freshly
      extracted human mandibular premolars were prepared by using Protaper (Dentsply
      Maillefer, Ballaigues, Switzerland) or the RaCe (FKG Dentaire, La Chaux-de-Fonds,
      Switzerland) systems (n=20 for each), after which half of the specimens were
      subjected to instrument separation at the apical level. Roots with and without
      apically separated instruments (n=5) were filled with the two obturation systems
      i.e. Thermafil and lateral compaction technique. The modified glucose penetration
      setup was used to assess the microleakage. The leakage data was statistically
      analyzed. RESULTS: The amount of leakage was significantly lower in specimens
      containing fractured instruments, regardless of the obturation method used. Roots
      obturated with Thermafil displayed significantly less leakage than cold lateral
      compaction technique, both, in the presence and absence of separated instruments.
      There was no significant difference among specimens prepared with ProTaper and
      RaCe when Thermafil obturation was done. But with cold lateral compaction
      technique, RaCe system showed less leakage as compared to ProTaper system.
      CONCLUSION: The type of obturation may play more important role than the type of
      instrument or retained/non-retained instrument factor.

PMID- 22368334
TI  - Relationship between sealing ability of Activ GP and Gutta Flow and methods of
      calcium hydroxide removal.
AB  - AIM: To evaluate the effect of method of calcium hydroxide intracanal dressing
      removal, on sealing ability of Gutta Flow and Activ GP. MATERIALS AND METHODS:
      Seventy extracted mandibular premolars were sectioned at CEJ and canals were
      prepared with profile 4% rotary file till #40. Canals were filled with calcium
      hydroxide, coronally sealed with Cavit G and stored at 37 degrees C. After 7
      days, samples were divided on the basis of calcium hydroxide removal method
      (Master apical file, Navi Tip FX, and F File) and obturating material (Activ GP
      and Gutta Flow). Three coats of nail polish were applied except 2 mm around
      apical foramen and samples were immersed in India ink dye, sectioned, and
      observed under stereomicroscope for microleakage. RESULTS: The results were
      statistically analyzed with one way ANOVA-F with Tukey HSD test with the null
      hypothesis set as 5%. CONCLUSIONS: The seal of the canal system was adversely
      impacted by residual calcium hydroxide when Activ GP and Gutta Flow were used as
      obturating material and the sealing ability of Activ GP and Gutta Flow was better
      when MAF was used for removal of calcium hydroxide than F file or Navi tip FX.

PMID- 22368335
TI  - Bactericidal effect of the 908 nm diode laser on Enterococcus faecalis in
      infected root canals.
AB  - AIM: The aim of this study is to evaluate the bactericidal effect of 908 nm diode
      laser in conjunction with various irrigation regimes in disinfection of apical
      third of root dentin. MATERIALS AND METHODS: Sixty prepared teeth with single
      canals were contaminated with Enterococcus faecalis. The specimens were divided
      into 6 groups (n = 10): Group 1 and 3 and 5 were subjected to chemo-mechanical
      preparation using 5.25% sodium hypochlorite (NaOCl), 17%
      Ethylenediaminetetraacetic acid (EDTA); 1.3% NaOCl, MTAD (mixture of doxycycline,
      citric acid and a detergent (Tween 80); and, 8.5% saline, respectively followed
      by 908 nm diode laser irradiation; Group 2 and 4, followed the same procedure as
      Group1 and 3, however without laser irradiation; and, Group 6, rinsed with saline
      solution (control). Dentin shavings from apical third were analyzed for the
      presence of E. faecalis using culture method and Polymerase Chain reaction (PCR).
      RESULTS: One-way Analysis of variance showed statistically significant
      differences between the laser irradiated groups, non irradiated groups and the
      control group. CONCLUSION: 908 nm diode used in conjunction with conventional
      chemomechanical techniques demonstrated a significant elimination of E. faecalis
      in the apical third of root dentin.

PMID- 22368336
TI  - Effect of 'Perceived control' in management of anxious patients undergoing
      endodontic therapy by use of an electronic communication system.
AB  - BACKGROUND: From time immemorial, fear and anxiety have been associated with
      dental treatment. Coping with this fear and anxiety has been one of the most
      vexing problems with which the individual dentist, as well as the profession has
      had to contend. Hence this study was undertaken to evaluate a new technique for
      management of such anxious patients. AIM: The aim of this study is to evaluate
      the efficacy of using 'Perceived control' for the management of anxious patients
      undergoing endodontic therapy. SETTINGS AND DESIGN: 'A communication device
      designed by the author and named as "Touch N' Tell" (Patent no: 234291,
      Government of India) was installed on the dental chair which helps to create an
      effective communique between the patient and dentist during the dental procedure.
      MATERIALS AND METHODS: Sixty anxious patients were selected using Modified Dental
      Anxiety Scale (MDAS), and were divided into two groups. For group A, the patients
      were treated along with the use of 'communication system' installed on the dental
      chair, whereas the patients were managed in a routine manner for Group B. The
      post operative MDAS scores were recorded for both the groups. STATISTICAL
      ANALYSIS: The mean change in anxiety levels was calculated for both the groups.
      Statistical analysis was done using unpaired t-test. RESULT AND CONCLUSION: A
      significant decrease in the mean anxiety levels was observed in the group where
      'communication system' was used as a measure of perceived control.

PMID- 22368337
TI  - Odontoplasty associated with clinical crown lengthening in management of
      extensive crown destruction.
AB  - AIM: The aim of this study was to evaluate the clinical outcome of teeth
      submitted to odontoplasty during clinical crown lengthening surgery (CCLS), when
      compared to their contralateral non-operated teeth. MATERIALS AND METHODS:
      Fourteen patients submitted to odontoplasty during CCLS were evaluated according
      to plaque index, bleeding on probing, probing depth and final restoration outcome
      (total success, relative success and failure). RESULTS: The mean follow-up period
      was 13.57 (+/- 8.00) months, and ranged from 6 to 24 months. Twelve cases
      presented total success of the final rehabilitation and 2 cases presented
      relative success. The cases of relative success were due to the necessity for a
      new periodontal intervention (scalling). No differences were observed with
      respect to periodontal parameters (P>0.05) and the patients that showed relative
      success presented generalized poor oral hygiene. CONCLUSIONS: The odontoplasty
      during clinical crown lengthening surgery is a feasible procedure in the
      management of extensive crown destruction.

PMID- 22368338
TI  - Remineralization of enamel subsurface lesions with casein phosphopeptide
      amorphous calcium phosphate: A quantitative energy dispersive X-ray analysis
      using scanning electron microscopy: An in vitro study.
AB  - AIM: The objective of this study was to quantitatively evaluate the
      remineralization potential of casein phosphopeptide-amor-phous calcium phosphate
      paste on enamel subsurface lesions using scanning electron microscopy with energy
      dispersive X-ray analysis (SEM-EDX). MATERIALS AND METHODS: Ninety enamel
      specimens were prepared from extracted human molars. All specimens were evaluated
      for mineral content (% weight) using SEM-EDX. The specimens were placed in
      demineralizing solution for four days to produce artificial carious lesions. The
      mineral content (calcium/phosphorus ratios, Ca/P ratios) was remeasured using SEM
      EDX. The specimens were then randomly assigned to five study groups and one
      control group of 15 specimens per group. Except for the control group, all group
      specimens were incubated in remineralizing paste (CPP-ACP paste) for 7, 14, 21,
      28, and 35 days twice daily for three minutes. The control group received no
      treatment with remineralizing paste. All the 90 specimens were stored in
      artificial saliva at 37 degrees C. After remineralization, the mineral content (%
      weight) of the samples was measured using SEM-EDX. RESULTS: All the study groups
      showed very highly significant differences between Ca/P ratios of the
      demineralized and remineralized samples. There was no significant difference seen
      in the control group. CONCLUSION: CPP-ACP paste could significantly remineralize
      the artificial enamel subsurface lesions in vitro: the remineralizing rates
      increasing with the time for which the samples were kept in the remineralizing
      paste. Energy dispersive X-ray analysis is an efficient way to quantitatively
      assess the changes in mineral content during demineralization and in vitro
      remineralization processes.

PMID- 22368339
TI  - Conventional apexification and revascularization induced maturogenesis of two non
      vital, immature teeth in same patient: 24 months follow up of a case.
AB  - Various authors have demonstrated the regenerative process in immature, non vital
      teeth by revascularization induced maturogenesis. The aim of this case report is
      to compare calcium hydroxide apexification and pulp revascularization induced
      maturation procedures in the same patient, in two different teeth. The right
      maxillary central incisor in this individual was treated with conventional
      calcium hydroxide induced apexification procedure followed by
      guttaperchaobturation, and the left maxillary central incisor was treated by pulp
      revascularization induced maturation procedures. 24 months follow-up shows root
      elongation and apical closure in the tooth treated with revascularization induced
      maturation procedures. Revascularization induced maturogenesis, where indicated,
      can provide several advantages over conventional apexification procedures.

PMID- 22368340
TI  - Mineral trioxide aggregate apical plug method for the treatment of nonvital
      immature permanent maxillary incisors: Three case reports.
AB  - Treatment of nonvital immature permanent teeth with calcium-hydroxide is
      associated with some difficulties such as weakened tooth fracture, root canal
      reinfection and long treatment time. Mineral trioxide aggregate (MTA) apical plug
      method is an alternative treatment option for open apices, and has gained
      popularity in the recent times. In this case report, we have attempted to present
      successful treatment of three maxillary incisors with open apices and periapical
      lesions with MTA. After preparing the access cavity, the working length was
      determined. The root canals were irrigated with 2.5% Sodium hypochlorite (NaOCl)
      and disinfected with calcium-hydroxide for two weeks. MTA was then placed in the
      apical 3 millimeters of the root canal. The remaining part of the root canal was
      filled with gutta-percha and the coronal restoration was finished with composite
      resin. After six months the radiographic examination showed a decrease of
      periapical lesions. At a 1-year and 18-months follow up, radiological and
      clinical successful healing of the incisor teeth was seen. MTA seems as an
      effective material for the apical plug method for the treatment of nonvital
      immature permanent teeth with open apices.

PMID- 22368341
TI  - Management and prognosis of teeth with trauma induced crown fractures and large
      periapical cyst like lesions following apical surgery with and without retrograde
      filling.
AB  - Crown fractures are common detrimental consequences of dental traumatic injuries.
      Early management of such cases is mandatory in order to prevent subsequent
      pathological changes that could further complicate the treatment. Pulp necrosis,
      chronic and cystic apical periodontitis can be the fate if these teeth are left
      untreated. Despite these serious complications, root canal treatment followed by
      apical surgery is considered a valid treatment option when such cases become
      complicated with large periapical lesions. However, whether a retrograde filling
      is essential to be placed or not is still a matter of debate. This case report
      discusses the orthograde endodontic management, the surgical approach and the
      clinical outcomes of longstanding crown fractured teeth with large cyst-like
      periapical lesions with and without retrograde filling.

PMID- 22368342
TI  - Tooth fragment reattachment technique on a pluri traumatized tooth.
AB  - This case report describes and analyses a tooth fragment reattachment technique
      used to resolve crown fractures of the anterior teeth. This treatment allows a
      conservative approach to traumatic coronal lesions offering a better possibility
      of maintaining aesthetics and function. The authors have illustrated here a
      clinical case of a fractured incisor. This case is characterized by several
      traumas on the same tooth that required different therapeutic solutions. We used
      an easy and ultra-conservative technique without any tooth preparation in the
      first and third traumatic injuries. In the second trauma, a direct restoration of
      the fractured tooth was performed. The adhesive reattachment is a simple system
      to achieve good aesthetic and functional results.Our clinical experiences
      demonstrated that, when tooth and fragment margins are intact, the reattachment
      technique without any tooth preparation is a simple and predictable procedure.
      Quality of adhesion is shown by the retention of the reattached fragment in the
      second trauma that caused only partial enamel fractures.

PMID- 22368343
TI  - Plexiform ameloblastoma mimicking a periapical lesion: A diagnostic dilemma.
AB  - Plexiform ameloblastoma is one of the variant of ameloblastoma, with specific
      histopathological features. It manifests as unilocular or multilocular
      radiolucencies in the mandible or maxilla. In very rare cases, it can appear as a
      localized periradicular radiolucent area and imitate an endodontic lesion.
      Reported here is a rare case of plexiform ameloblastoma in an uncommon location,
      which was misdiagnosed as periapical lesion of inflammatory origin and treated
      endodontically. Surgical enucleation was followed and diagnosis of plexiform
      ameloblastoma was confirmed on histological grounds.

PMID- 22368344
TI  - A facial talon cusp on maxillary permanent central incisors.
AB  - Talon cusp is a dental anomaly that occurs as an accessory cusp like structure,
      from the cingulum of maxillary and mandibular anterior teeth. Lingual location is
      usually considered pathognomic. This case report discuss about the unusual
      appearance of talon cusp on the facial surface of the maxillary left permanent
      central incisor and a mild talon cusp on the facial surface of the maxillary
      right permanent central incisor.

PMID- 22368345
TI  - Endodontic management of a patient with oral submucous fibrosis using custom
      modified endodontic instruments.
AB  - This case report presents the endodontic management of a patient diagnosed with
      oral submucous fibrosis (OSMF), and with a reduced mouth opening of 18 mm. The
      patient presented with acute pain; and, emergency pulpectomy was performed using
      modified endodontic instruments. Treatment of OSMF was initiated and the
      endodontic treatment was completed at a late stage. The article discusses in
      brief the etio-pathogenesis of OSMF with endodontic management of such patients.

PMID- 22368346
TI  - Morality, ethics, norms and research misconduct.

PMID- 22368347
TI  - Author's reply.

PMID- 22368348
TI  - Event Report- 26FODI and 19 IES National Conference, New Delhi, 2011.

PMID- 22368349
TI  - What is the measure of perfection?

PMID- 22368350
TI  - Firm on the ground....

PMID- 22368351
TI  - Effect of local drug delivery in chronic periodontitis patients: A meta-analysis.
AB  - Periodontal diseases are multi-factorial in etiology, and bacteria are one among
      these etiologic agents. Thus, an essential component of therapy is to eliminate
      or control these pathogens. This has been traditionally accomplished through
      mechanical means (scaling and root planing (SRP)), which is time-consuming,
      difficult, and, sometimes, ineffective. From about the past 30 years, locally
      delivered, anti-infective pharmacological agents, most recently employing
      sustained-release vehicles, have been introduced to achieve this goal. This
      systematic review is an effort to determine the efficacy of the currently
      available anti-infective agents, with and without concurrent SRP, in controlling
      chronic periodontitis. Four studies were included, which were all randomized
      controlled trials, incorporating a total patient population of 80, with 97
      control sites and 111 test sites. A meta-analysis completed on these four studies
      including SRP and local sustained-release agents compared with SRP alone
      indicated significant adjunctive probing depth (PD) reduction for 10% Doxycycline
      hycylate (ATRIDOX), minocycline hydrochloride (ARESTIN), tetracycline
      hydrochloride (PERIODONTAL PLUS AB), and chlorhexidine gluconate (PERIOCHIP).
      Essentially, all studies reported substantial reductions in gingival
      inflammation, plaque scores, and bleeding indices, which were similar in both the
      control and the experimental groups. Use of antimicrobial sustained-release
      systems as an adjunct to SRP does not result in significant patient-centered
      adverse events. Local drug delivery combined with SRP appears to provide
      additional benefits in PD reduction compared with SRP alone.

PMID- 22368353
TI  - "What is there in a name?": A literature review on chronic and aggressive
      periodontitis.
AB  - The objective of this review is to bring the reader up-to-date on the current
      understanding of chronic and aggressive forms of periodontitis and the
      implications for diagnosis and treatment of these diseases. The only difference
      between chronic periodontitis and aggressive periodontitis with regard to tissue
      destruction appear to be perhaps the magnitude, sequelae, and control of the
      response. While there may be some differences in the cellular infiltrate between
      these two diseases, the molecular mediators and pathologic processes are
      generally the same.

PMID- 22368352
TI  - Saliva: A diagnostic biomarker of periodontal diseases.
AB  - Early detection of disease plays a crucial role in successful therapy. Early
      diagnosis and management reduces the severity and possible complications of the
      disease process. To overcome this challenge, medical researchers are devoted to
      finding molecular disease biomarkers that reveal a hidden lethal threat before
      the disease becomes complicated. Saliva, an important physiologic fluid,
      containing a highly complex mixture of substances, is rapidly gaining popularity
      as a diagnostic tool. Periodontal disease is a chronic disease of the oral cavity
      comprising a group of inflammatory conditions affecting the supporting structures
      of the dentition. In the field of periodontology, traditional clinical criteria
      are often insufficient for determining sites of active disease, for monitoring
      the response to therapy, or for measuring the degree of susceptibility to future
      disease progression. Saliva, as a mirror of oral and systemic health, is a
      valuable source for clinically relevant information because it contains
      biomarkers specific for the unique physiologic aspects of periodontal diseases.
      This review highlights the various potentials of saliva as a diagnostic biomarker
      for periodontal diseases.

PMID- 22368354
TI  - Antimicrobial photodynamic therapy: An overview.
AB  - Inflammatory periodontal disease caused by dental plaque is characterized by the
      clinical signs of inflammation and loss of periodontal tissue support. The
      mechanical removal of this biofilm and adjunctive use of antibacterial
      disinfectants and antibiotics have been the conventional methods of periodontal
      therapy. But the removal of plaque and the reduction in the number of infectious
      organisms can be impaired in sites with difficult access. The possibility of
      development of resistance to antibiotics by the target organism has led to the
      development of a new antimicrobial concept with fewer complications. Photodynamic
      therapy (PDT) involves the use of low power lasers with appropriate wavelength to
      kill micro organisms treated with a photosensitizer drug. PDT could be a useful
      adjunct to mechanical as well as antibiotics in eliminating periopathogenic
      bacteria.

PMID- 22368356
TI  - Minimally invasive periodontal therapy.
AB  - Minimally invasive dentistry is a concept that preserves dentition and supporting
      structures. However, minimally invasive procedures in periodontal treatment are
      supposed to be limited within periodontal surgery, the aim of which is to
      represent alternative approaches developed to allow less extensive manipulation
      of surrounding tissues than conventional procedures, while accomplishing the same
      objectives. In this review, the concept of minimally invasive periodontal surgery
      (MIPS) is firstly explained. An electronic search for all studies regarding
      efficacy and effectiveness of MIPS between 2001 and 2009 was conducted. For this
      purpose, suitable key words from Medical Subject Headings on PubMed were used to
      extract the required studies. All studies are demonstrated and important results
      are concluded. Preliminary data from case cohorts and from many studies reveal
      that the microsurgical access flap, in terms of MIPS, has a high potential to
      seal the healing wound from the contaminated oral environment by achieving and
      maintaining primary closure. Soft tissues are mostly preserved and minimal
      gingival recession is observed, an important feature to meet the demands of the
      patient and the clinician in the esthetic zone. However, although the potential
      efficacy of MIPS in the treatment of deep intrabony defects has been proved,
      larger studies are required to confirm and extend the reported positive
      preliminary outcomes.

PMID- 22368357
TI  - Effect of smoking on gingival microvasculature: A histological study.
AB  - BACKGROUND: Smoking has been reported as a major risk factor for periodontal
      disease. Studies have demonstrated decreased bleeding on probing and reduced
      inflammatory response among smokers, which has been attributed to the alterations
      in gingival microvasculature, gingival epithelium. In previous investigations,
      vascular and epithelial changes have been studied in the gingival tissues of
      smokers suffering from periodontitis and compared with healthy periodontium of
      non smokers. Inflammation is known to cause vascular and epithelial changes in
      the gingiva on its own in the absence of smoking. Hence, in the present
      investigation, an attempt is made to study and to compare the vascular and
      epithelial changes in the gingiva of smokers and non smokers suffering from
      chronic periodontitis. AIM OF STUDY: The purpose of this study was to evaluate
      the vascular and epithelial changes in gingiva of smokers and non smokers with
      chronic periodontitis. STUDY DESIGN: Cross sectional study MATERIALS AND METHODS:
      Gingival biopsies were obtained from 33 male patients (18 smokers and 15 non
      smokers) who were undergoing periodontal therapy or extraction. The sections were
      stained with eosin and hematoxylin. Vascular density, area of the lumen, and
      epithelial thickness were assessed using histomorphometric image analysis.
      STATISTICAL METHOD: Data was analyzed using student unpaired 't' test, Karl
      Pearsons correlation, and Chi-square test. RESULTS: The mean blood vessel density
      for smokers was 12.388+/-6.472 and for non smokers was 14.800+/-4.91. The mean
      lumen area of the vessels among smokers and non smokers was 19.290+/-8.775 MUm(2)
      and 20.044+/-7.896 MUm(2), respectively. The mean epithelial thickness among
      smokers was 150.551+/-32.994 MU and 134.941+/-30.63 MU for non smokers.
      CONCLUSION: Based on the present histomorphometric study, it could be concluded
      that smokers have less vascular density and reduced lumen area and increased
      epithelial thickness than non smokers. However, these changes were not
      statistically significant.

PMID- 22368355
TI  - Tissue engineering: A new vista in periodontal regeneration.
AB  - Tissue engineering is a highly promising field of reconstructive biology that
      draws on recent advances in medicine, surgery, molecular and cellular biology,
      polymer chemistry, and physiology. The objective of using tissue engineering as
      therapeutic application has been to harness its ability to exploit selected and
      primed cells together with an appropriate mix of regulatory factors, to allow
      growth and specialization of cells and matrix. The authors reviewed controlled
      clinical trials which also included histological studies that evaluated the
      potential of tissue engineering as a clinical tool in regeneration.
      PubMed/MEDLINE databases were searched for studies up to and including June 2010
      to identify appropriate articles. A comprehensive search was designed, and the
      articles were independently screened for eligibility. Articles with authentic
      controls and proper randomization and pertaining specifically to their role in
      periodontal regeneration were included. Studies demonstrated that the periodontal
      regeneration with the use of combination of tissue engineered products with an
      osteoconductive matrix improve the beneficial effect of these materials by
      accelerating cellular in growth and revascularization of the wound site. Studies
      have suggested the use of rh Platelet-derived growth factor + beta tricalcium
      phosphate for regeneration of the periodontal attachment apparatus in combination
      with collagen membranes as an acceptable alternative to connective tissue graft
      for covering gingival recession defects. The studies concluded that growth
      factors promote true regeneration of the periodontal attachment apparatus and the
      use of combination protein therapeutics which is commercially available can
      provide more predictable, faster, less invasive, less traumatic, and efficient
      outcome for the patient.

PMID- 22368358
TI  - Comparison of the effectiveness of a commercially available herbal mouthrinse
      with chlorhexidine gluconate at the clinical and patient level.
AB  - BACKGROUND: The key to good oral health is hidden in nature. Natural herbs like
      neem, tulsi, pudina, clove oil, ajwain, triphala and many more has been used
      since ages either as a whole single herb or as a combination against various oral
      health problems like bleeding gums, halitosis, mouth ulcers and preventing tooth
      decay. The aim of the study was to compare the efficacy of a commercially
      available herbal mouthrinse (Herboral) with that of chlorhexidine gluconate which
      is considered to be a gold standard as an anti-plaque agent. MATERIALS AND
      METHODS: A randomized, two-group, parallel study as a 'de novo' plaque
      accumulation model was carried out on 50 subjects (23 males and 27 females). At
      baseline, all participants received a professional prophylaxis and were randomly
      assigned to the test (Herbal mouthrinse) and control (Chlorhexidine Gluconate)
      group. On the following three days, all subjects rinsed with 10 ml of the
      allocated mouthrinse twice daily for 1 min. They were asked to refrain from use
      of any other oral hygiene measures during the study. At the end of the
      experimental period, plaque was assessed and a questionnaire was filled by all
      subjects. RESULTS: Chlorhexidine (mean plaque score=1.65) inhibited plaque growth
      significantly more than the herbal mouthrinse (mean plaque score=1.43, P<0.001).
      The results of the questionnaire showed that Herboral was preferred by patients
      for its taste, its convenience of use and taste duration (aftertaste). However,
      Chlorhexidine was considered to be more effective in reducing plaque as compared
      to Herboral. CONCLUSION: Herbal mouthrinse was found to be a potent plaque
      inhibitor, though less effective than Chlorhexidine Gluconate. However, it can
      serve as a good alternative for the patients with special needs as in case of
      diabetics, xerostomics, and so on.

PMID- 22368359
TI  - Comparative evaluation of a bioabsorbable collagen membrane and connective tissue
      graft in the treatment of localized gingival recession: A clinical study.
AB  - BACKGROUND: Gingival recession (GR) can result in root sensitivity, esthetic
      concern to the patient, and predilection to root caries. The purpose of this
      randomized clinical study was to evaluate (1) the effect of guided tissue
      regeneration (GTR) procedure using a bioabsorbable collagen membrane, in
      comparison to autogenous subepithelial connective tissue graft (SCTG) for root
      coverage in localized gingival recession defects; and (2) the change in width of
      keratinized gingiva following these two procedures. MATERIALS AND METHODS: A
      total of 10 cases, showing at least two localized Miller's Class I or Class II
      gingival recession, participated in this study. In a split mouth design, the
      pairs of defects were randomly assigned for treatment with either SCTG (SCTG
      Group) or GTR-based collagen membrane (GTRC Group). Both the grafts were covered
      with coronally advanced flap. Recession depth (RD), recession width (RW), width
      of keratinized gingiva (KG), probing depth (PD), relative attachment level (RAL),
      plaque index (PI), and gingival index (GI) were recorded at baseline, 3 and 6
      months postoperatively. RESULTS: Six months following root coverage procedures,
      the mean root coverage was found to be 84.84% +/- 16.81% and 84.0% +/- 15.19% in
      SCTG Group and GTRC Group, respectively. The mean keratinized gingival width
      increase was 1.50 +/- 0.70 mm and 2.30 +/- 0.67 mm in the SCTG and GTRC group,
      respectively, which was not statistically significant. CONCLUSION: It may be
      concluded that resorbable collagen membrane can be a reliable alternative to
      autogenous connective tissue graft in the treatment of gingival recession.

PMID- 22368360
TI  - Causal relationship between periodontitis and chronic obstructive pulmonary
      disease.
AB  - CONTEXT: Recently, it has been recognized that oral infection, especially
      periodontitis, may affect the course and pathogenesis of a number of systemic
      diseases. An association between periodontal disease and chronic obstructive
      pulmonary disease (COPD) has been observed. AIMS: The aim of the present study
      was to evaluate the potential association between periodontal health and COPD and
      to assess the potential health status of patients with and without COPD. SETTINGS
      AND DESIGN: In this observational study, the association between periodontal
      disease and COPD has been assessed. MATERIALS AND METHODS: HUNDRED PATIENTS WERE
      CHOSEN FOR THE STUDY: group A comprising 50 COPD patients and group B consisting
      of 50 patients without COPD. Gingival Index (GI) and Papilla Bleeding Index (PBI)
      were used to assess the gingival status. Periodontal indices included Russell's
      Periodontal Index (PI) and Periodontal Index for Risk of Infectiousness (PIRI),
      which were assessed in all 100 patients. Analysis of covariance (ANCOVA) was the
      statistical analysis used. RESULTS: After eliminating age affects using ANCOVA,
      the mean indices of all variables between groups were found to be highly
      significant (P<0.001). The scores were highly significant in COPD group than in
      non-COPD group. CONCLUSIONS: The findings of the present study show that there is
      an association between periodontal disease and COPD. It is suggested that
      periodontitis is one of the risk factors for COPD.

PMID- 22368362
TI  - Effect of a volatile smoke component (acrolein) on human gingival fibroblasts: An
      in vitro study.
AB  - AIM: Tobacco and some of its volatile and non-volatile components have been found
      to affect many types of cells including human gingival fibroblasts. The aim of
      this present study was to estimate the effect of acrolein, a volatile fraction of
      cigarette smoke on the attachment, proliferation and ultra structure of human
      gingival fibroblasts in culture. MATERIALS AND METHODS: Human gingival
      fibroblasts strains obtained from healthy subjects aged 20-30 years, were grown
      to confluency and utilized between 3(rd) -6(th) passages. The cell cultures
      seeded in 96 well microtitration plates at a density of 45,000 cells/well were
      incubated with acrolein at concentrations of 10(-4), 3*10(-5) and 10(-5) .
      Attachment ability was evaluated after three hours using Neubauer hemocytometer.
      For the proliferation assay cell cultures seeded at a density of 10,000
      cells/well were incubated at concentrations of 10(-4), 3*10(-5), 10(-5), 3*10(
      6), 10(-6) and cell count determined after 5 days using a hemocytometer. Cell
      morphology was examined under phase contrast microscope. RESULTS: Acrolein
      produced a dose-dependent cytotoxic effect on human gingival fibroblasts with
      complete inhibition of attachment and proliferation at higher concentrations.
      CONCLUSION: This supports the hypothesis that cigarette smoke is a great risk
      factor in the development and progression of periodontal disease.

PMID- 22368361
TI  - Analysis of association between TLR-4 Asp299Gly and Thr399Ile gene polymorphisms
      and chronic periodontitis in a sample of south Indian population.
AB  - BACKGROUND: To analyze the association between TLR-4 Asp299Gly and Thr399Ile gene
      polymorphisms and chronic periodontitis in a sample of south Indian population.
      MATERIALS AND METHODS: Genomic DNA was obtained from peripheral blood of 60
      patients with chronic periodontitis and 60 periodontally healthy subjects. TLR-4
      Asp299Gly and Thr399Ile gene polymorphisms were genotyped by a polymerase chain
      reaction-restriction fragment length polymorphism method. The data were analyzed
      by a chi(2)-test and by relative risk estimation. RESULTS: Thr399Ile alleles were
      found in 4% of chronic periodontitis patients and in 1% of periodontally healthy
      subjects. The prevalence of a Thr399Ile heterozygote was found to be 5% in the
      chronic periodontitis group and 1.67% in the periodontally healthy group,
      respectively. Homozygosity for TLR-4 Thr399Ile was seen in chronic periodontitis
      patients only, which was 1.67%. The TLR-4 Asp299Gly gene polymorphism was not
      detected in either chronic periodontitis or periodontally healthy groups.
      CONCLUSION: There is no significant association between TLR-4 Thr399Ile
      polymorphism and chronic periodontitis in a sample of south Indian population.

PMID- 22368363
TI  - Evaluation of gingival fiber retention technique on the treatment of patients
      with chronic periodontitis: A comparative study.
AB  - The destructive action of the chronic periodontitis on the periodontal tissues
      has provided a continuous challenge to the dental profession to develop better
      methods to achieve repair of the recession regions and even regeneration of post
      periodontal tissues. AIMS: To assess the effect of periodontal muco-periostal
      flap surgery with gingival fiber retention technique on minimizing the post
      surgical recession. MATERIALS AND METHODS: The sample for the study comprised of
      20 patients. The criteria for selection included patients with moderate
      periodontitis, with minimum recession in the anterior teeth, with adequate width
      of the attached gingiva, and with no traumatic occlusion. Periodontal muco
      periosteal flap surgery with gingival fiber retention technique was done in the
      experimental site with internal bevel incision, and in control site, muco
      periosteal flap surgery with crevicular incision was done. Thereafter,
      observation period was of one week, four weeks, and eight weeks were done for
      both the sites. STATISTICAL ANALYSIS USED: The results were subjected to
      statistical analysis using student's t'-test. RESULTS: The result of this study
      suggests that the periodontal flap surgery with gingival fiber retention
      technique has a beneficial effect on the anterior teeth, as it maintains the
      esthetics, recontours the gingiva with minimal recession. The area of recession
      was more on the control site as compared to experimental site at 4 weeks, 8 weeks
      and 12 weeks. CONCLUSIONS: Gingival fiber retention technique showed less post
      surgical recession and also there was fall in values of plaque index, gingival
      index, and periodontal index scores, throughout the study.

PMID- 22368364
TI  - Effect of cigarette smoking on the periodontal health status: A comparative,
      cross sectional study.
AB  - CONTEXT: Survey. AIMS: The objective of the study was to evaluate the periodontal
      health status among cigarette smokers and non cigarette smokers, and oral hygiene
      measures. SETTINGS AND DESIGN: Cross sectional study. MATERIALS AND METHODS: The
      study included 400 male (200 cigarette smokers and 200 non smokers) aged 18-65
      years. The subjects were randomly selected from the patients attending dental out
      patient department of civil hospital and Himachal Dental College, Sundernagar.
      Community Periodontal Index (CPI) score was recorded for each patient and a
      questionnaire was completed by each patient. STATISTICAL ANALYSIS USED: Chi
      square and t-test. RESULTS: Periodontal condition as assessed by CPI score showed
      that there was statistically significant difference in the findings between
      cigarette smokers and non-smokers. CONCLUSIONS: Within the limits of this study,
      positive association was observed between periodontal disease and cigarette
      smoking. It was found that cigarette smoking was associated with lesser gingival
      bleeding and deeper pockets as compared to non-smokers.

PMID- 22368365
TI  - A clinical study of the relationship between diabetes mellitus and periodontal
      disease.
AB  - The relationship between diabetes mellitus and periodontal disease is not clear,
      even though studied intensively. From the available data, it seemed reasonable to
      believe that diabetics were more susceptible to periodontal disease than
      non.diabetics. AIM: The present study was to clinically evaluate the relationship
      of diabetes mellitus with periodontal disease along with various parameters.
      MATERIALS AND METHODS: Fifteen hundred patients with diabetes mellitus were
      examined. A thorough oral examination was carried out and relevant history was
      recorded for all the patients. RESULTS: Results indicated that the prevalence of
      periodontal disease in diabetic patients was 86.8%. CONCLUSION: It can be
      concluded that poorer the glycemic control, and longer the duration of diabetes,
      the greater will be the prevalence and severity of periodontal disease.

PMID- 22368366
TI  - An evaluation of a resorbable (semirigid) GTR membrane in human periodontal
      intraosseous defects: A clinicoradiological re-entry study.
AB  - AIM: To evaluate the effectiveness of a resorbable, semi rigid guided tissue
      regeneration (GTR) membrane in the treatment of periodontal intraosseous defects.
      SETTINGS AND DESIGN: Randomized controlled clinicoradiological re-entry study.
      MATERIALS AND METHODS: Eight patients with bilateral, identical intraosseous
      defects were selected. The sides for test and control group were randomly
      allocated to treat either with bioresorbable semi rigid membrane (test group) or
      open flap debridement (control group). Radiographic analysis was done by
      comparing intraoral peri apical radiographs taken at baseline and at six months.
      Extended cone paralleling device with grid was used to standardize radiographs.
      Auto CAD software was used for the analysis. STATISTICAL ANALYSIS USED: Paired-t
      test. RESULTS: On surgical reentry at six months, the mean reduction in depth of
      the defect at the test site was 2.63 mm. The mean gain in Relative attachment
      level was 1.75 mm. The control sites showed a statistically insignificant gain.
      The mean percentage defect fill assessed on radiographs using auto CAD software
      was 15.54%. CONCLUSION: The resorbable, semi-rigid GTR membrane can be
      effectively used for the treatment of human one-walled angular defects.

PMID- 22368367
TI  - To evaluate the antigingivitis and antipalque effect of an Azadirachta indica
      (neem) mouthrinse on plaque induced gingivitis: A double-blind, randomized,
      controlled trial.
AB  - BACKGROUND: Azadirachta indica (neem), a Meliaceae family tree, has been used in
      India for several decades for the treatment of several diseases in medicine and
      dentistry. Neem has been considered to have antiseptic activity, but still its
      use for the treatment of gingivitis and periodontitis is not very clear. Hence,
      the purpose of the present study was to assess the efficacy of neem based mouth
      rinse regarding its antigingivitis effect. MATERIALS AND METHODS: Forty five
      subjects with plaque induced gingivitis were selected for the study. They were
      equally divided into three groups. Group I patients were asked to rinse with 15
      ml of neem mouthwash twice daily, group II with 15 ml of chlorhexidine mouthwash
      twice daily, and group III with 15 ml of saline twice daily. The three groups
      were asked to perform the routine oral hygiene procedures thought out the study
      period. Bleeding on probing and gingivitis were evaluated by Muhlemann and Son's
      Sulcus bleeding index (1971) and Loe and Sillness gingival index (1963),
      respectively, at base line, after every week till one month. RESULTS: Our result
      showed that an A. indica mouthrinse is equally effective in reducing periodontal
      indices as Chlorhexidine. The results demonstrated a significant reduction of
      gingival, bleeding, and plaque indices in both groups over a period of 21 days as
      compared to placebo. CONCLUSION: A. indica-based mouth rinse is equally
      efficacious with fewer side effects as compared to chlorhexidine and may be used
      as an adjunct therapy in treating plaque induced gingivitis.

PMID- 22368368
TI  - Comparison between scalpel technique and electrosurgery for depigmentation: A
      case series.
AB  - A beautiful smile definitely enhances the personality of an individual and
      reveals self-confidence. The harmony of the smile is determined not only by the
      shape, position, and color of the teeth but also by the gingival tissues.
      Gingival pigmentation results from melanin granules which are produced by
      melanoblasts. Although melanin pigmentation of the gingiva is a completely benign
      condition and does not pose any medical problem, complaints of "black gums" are
      common particularly in patients having a very high smile line. The different
      treatment modalities that have been reported for depigmentation are bur abrasion,
      partial thickness flap, cryotherapy, electrosurgery, and lasers. In this paper we
      have compared the results of electrosurgery and scalpel technique, i.e., partial
      thickness flap.

PMID- 22368369
TI  - Treatment and two-year follow-up of a patient with hereditary gingival
      fibromatosis.
AB  - Hereditary gingival fibromatosis is a rare disorder characterized by various
      degrees of attached gingival overgrowth. Gingival fibromatosis usually develops
      as an isolated disorder but can be one feature of a syndrome. A case of a 17-year
      old female who presented with a generalized severe gingival overgrowth, involving
      the maxillary and mandibular arches and covering almost the whole dentition.
      Excess gingival tissue was removed by conventional gingivectomy under local
      anesthesia. The postoperative course was uneventful and the patient's appearance
      improved considerably. Good esthetic result was achieved without recurrence of
      the gingival overgrowth. After treatment, regular recall visits are necessary in
      order to evaluate oral hygiene, and the stability of the periodontal treatment.

PMID- 22368370
TI  - Guided tissue regeneration in communicating periodontal and endodontic lesions -
      A hope for the hopeless!
AB  - The use of guided tissue regeneration (GTR) has become a standard of care in
      Periodontology. GTR using membrane barriers and/or bone grafting materials has
      also been used in periapical surgery. However, the application of the GTR
      principle, particularly in communicating endodontic-periodontal lesions with loss
      of the buccal cortical plate, is a very challenging task, with very few reported
      human clinical studies. An interdisciplinary approach, combining endodontic and
      periodontal (surgical) procedures can save a tooth in the long run that has been
      defined as hopeless at the preliminary stage of treatment.

PMID- 22368371
TI  - Ortho-perio integrated approach in periodontally compromised patients.
AB  - It is an undisputed fact that sound and strong periodontal health is a must in
      patients seeking orthodontic treatment. Does this mean that we are going to deny
      orthodontic treatment for those adults whose number is rising, more often
      secondary to periodontal deterioration and pathological migration of teeth
      resulting in aesthetic and functional problems? Need of the hour is to have an
      integrated approach where in periodontal treatment precedes orthodontic treatment
      to restore periodontal health. Orthodontic treatment should be performed under
      strict plaque control measures to place the teeth in a structurally balanced and
      functionally efficient position. Aim of this article is to familiarize the
      practicing clinicians both in the field of orthodontics and periodontics with
      current thoughts and successful clinical techniques used in the field of
      periodontology to regenerate lost periodontal structures. Furthermore, it aims to
      integrate such techniques into the orthodontic treatment of patients with severe
      bone loss.

PMID- 22368372
TI  - Extranodal non-Hodgkin's lymphoma presenting as gingival mass.
AB  - Non-Hodgkin's lymphoma (NHL) commonly presents as non-tender, enlarged lymph
      nodes, accompanied by diffuse symptoms of fatigue and low-grade intermittent
      fever and it is derived predominantly from the cells of the B lymphocyte series.
      NHL cases occur extra-nodally and in 3% of these cases the initial presentation
      may be in the oral cavity. Though extra-nodal NHL of the oral cavity is a rare
      finding, patients with oral lesions of NHL commonly present at the dental clinic
      in the first instance. A careful clinical evaluation supported by
      histopathological and other laboratory investigations will help in identifying
      the disease at an early stage, resulting in better prognosis. Any delay in
      diagnosis has important implications on the morbidity and mortality of the
      condition. Due to the rarity of intraoral NHL, we present one such a case with a
      complaint of tumor-like mass on the gingiva of lower molar region. The lesion was
      clinically thought as pyogenic granuloma and later diagnosed as extra nodal NHL
      of the oral cavity.

PMID- 22368373
TI  - Correction of gummy smile: A report of two cases.
AB  - Cosmetically acceptable smiles show a gingival display of up to 3 mm. Gingival
      display of greater than 3 mm results in a gummy smile which is often unsightly
      for the individual and correction is sought. There are a variety of procedures
      used for surgical crown lengthening. Here, we describe two such cases requiring
      two different approaches for surgical crown lengthening.

PMID- 22368375
TI  - Ablation of Ventricular Arrhythmias in GUCH: The Surgical Scar and the Second
      Substrate.

PMID- 22368374
TI  - Oral malignant melanoma: A silent killer?
AB  - Oral malignant melanomas are extremely rare lesions and occur commonly in the
      maxillary gingiva more frequently on the palate with fewer incidences in the
      mandibular gingiva. Though these lesions are biologically aggressive, they often
      go unnoticed since they are clinically asymptomatic in the early stages and
      usually present merely as a hyperpigmented patch on the gingival surface. These
      lesions if diagnosed at an early in situ stage are potentially curable and
      definitely have a better prognosis, but unfortunately as they are clinically
      asymptomatic, it results in delayed diagnosis thus making the prognosis extremely
      poor. This paper presents the case of a patient who visited our department with
      the complaint of darkened patches on the gums and his concern was purely
      aesthetic. There were no symptoms associated with the hyperpigmented lesions and
      hence the patient did not approach us earlier. When the lesions grew larger and
      were unsightly, the patient has seeked dental advice. Histopathologic
      investigation confirmed the diagnosis as 'Oral Malignant Melanoma'. Though
      aggressive therapy was instilled immediately, unfortunately, the patient
      succumbed to death within a few months after diagnosis as the lesion was highly
      invasive. Due to the biologically aggressive but clinically silent nature of
      progression of the lesion, the importance of maintaining a high index of
      suspicion and early detection and diagnosis for any pigmented gingival lesions
      cannot be overemphasised. Diagnosis must be based on thorough detailed history
      and valid histologic evidence.

PMID- 22368376
TI  - Right ventricular pacing and sensing function in high posterior septal and apical
      lead placement in cardiac resynchronization therapy.
AB  - BACKGROUND: The conventional right ventricular (RV) lead position in cardiac
      resynchronization therapy pacemakers (CRT-P) is the RV apex (RV-A). Little is
      known about electrophysiological stability and associated complications of pacing
      leads in RV high posterior septal (RV-HS) position in CRT-P. METHODS: Two hundred
      and thirty-five consecutive CRT-P patients were included from 1999-2010. Pacing
      thresholds at 0.5ms and 2.5V, sensing electrograms and lead impedances were
      measured at implant and repeated 1,3,6,12,18 and 24 months after CRT-P.
      Electrophysiological measurements of leads located in RV-A and RV-HS were
      analyzed retrospectively. Bipolar RV leads were used, including high impedance
      leads, passive fixation and active fixation. RESULTS: RV pacing leads were
      implanted in RV-A (n=79) and RV-HS (n=156). Average RV pacing thresholds from CRT
      implant procedure to 24-month follow-up at 0.5ms were 0.77+/-0.69V in RV-A and
      0.71+/-0.35V in RV-HS (P=0.31), and at 2.5V were 0.06+/-0.08ms in RV-A and 0.07+/
      0.05ms in RV-HS (P=0.12). Average RV electrogram amplitudes from baseline to 24
      months after CRT were 15.3+/-6.9mV in RV-A and 12.1+/-6.0mV in RV-HS (P=0.55).
      Average RV impedances during follow-up were 850+/-286Omega in RV-A and 618+/
      147Omega in RV-HS (P=0.57). Similar RV lead revisions between RV-A and RV-HS were
      observed after 2-year follow-up (P=0.55). CONCLUSION: The RV-HS lead position
      demonstrated stable and acceptable long-term pacing and sensing function, with
      rates of complications comparable to conventional RV-A lead position in CRT. The
      RV-HS lead position is feasible in CRT-P.

PMID- 22368377
TI  - Unusual signals in a halo catheter: what is the mechanism?
AB  - In this "featured arrhythmia" article we present a set of unusual intracardiac
      electrode tracings that were recorded in a patient with typical clockwise flutter
      but a very dilated right atrium. The potential mechanism underlying this
      phenomenon is discussed with reference to the current literature.

PMID- 22368379
TI  - Ventricular Tachycardia Precipitated by Short-long-short Sequence in a Patient
      with Implantable-cardioverter Defibrillator.
AB  - Abrupt changes in heart rate, particularly short-long-short sequences in the
      ventricular cycle length (CL), might precede initiation of ventricular
      tachycardia/fibrillation (VT/VF). These changes may be facilitated or caused by
      pacing activity in patients with pacemakers or implantable-cardioverter
      defibrillators (ICDs). We describe a patient with two episodes of acquired VT
      precipitated by short-long-short sequences and diagnosed from the ICD recordings.
      In such cases, the knowledge of the device parameters is extremely important for
      a correct diagnosis and management.

PMID- 22368378
TI  - Paroxysmal atrial fibrillation triggered by a monomorphic ventricular couplet in
      a patient with acute coronary syndrome.
AB  - Atrial fibrillation is a common arrhythmia in patients suffering from acute
      myocardial infarction, however its pathophysiological mechanisms are not fully
      understood. We describe the unusual case of a 76-year old woman admitted for non
      ST-segment elevation myocardial infarction, who developed multiple episodes of
      paroxysmal atrial fibrillation triggered by monomorphic ventricular couplets.
      Beta-blocking and amiodarone therapy resulted efficacious in preventing
      arrhythmic recurrences. We then discuss the possible arrhythmogenic mechanisms,
      with special emphasis on the unique electrophysiological, hemodynamic, cellular
      and anatomical milieu created by acute myocardial ischemia.

PMID- 22368380
TI  - Ventricular tachycardia in repaired double chambered right ventricle -
      identification of the substrate and successful ablation.
AB  - A 35 year old female presented with recurrent ventricular tachycardia 5 years
      after she had undergone surgical repair of double chambered right ventricle.
      Electroanatomical mapping showed a localised scar in the apex with double
      potentials and good pace map. Ablation here resulted in non-inducibility of
      ventricular tachycardia. We hypothesise that the scarring in the apex is the
      result of sustained pressure overload and becomes arrhythmogenic similar to the
      apical scar in patients with mid-ventricular hypertrophic cardiomyopathy.

PMID- 22368381
TI  - Mouse heart rate in a human: diagnostic mystery of an extreme tachyarrhythmia.
AB  - We report telemetry recording of an extreme non-fatal tachyarrhythmia noted in a
      hospitalized quadriplegic male with history of atrial fibrillation where the
      average ventricular conduction rate was found to be about 600 beats per minute
      and was associated with transient syncope. A medical literature review suggests
      that the fastest human ventricular conduction rate reported to date in a
      tachyarrhythmia is 480 beats per minute. We therefore report the fastest human
      heart rate noted in a tachyarrhythmia and the most probable mechanism of this
      arrhythmia being a rapid atrial fibrillation with 1:1 conduction in the setting
      of probable co-existing multiple bypass tracts.

PMID- 22368382
TI  - Mining and gene ontology based annotation of SSR markers from expressed sequence
      tags of Humulus lupulus.
AB  - Humulus lupulus is commonly known as hops, a member of the family moraceae.
      Currently many projects are underway leading to the accumulation of voluminous
      genomic and expressed sequence tag sequences in public databases. The genetically
      characterized domains in these databases are limited due to non-availability of
      reliable molecular markers. The large data of EST sequences are available in
      hops. The simple sequence repeat markers extracted from EST data are used as
      molecular markers for genetic characterization, in the present study. 25,495 EST
      sequences were examined and assembled to get full-length sequences. Maximum
      frequency distribution was shown by mononucleotide SSR motifs i.e. 60.44% in
      contig and 62.16% in singleton where as minimum frequency are observed for
      hexanucleotide SSR in contig (0.09%) and pentanucleotide SSR in singletons
      (0.12%). Maximum trinucleotide motifs code for Glutamic acid (GAA) while AT/TA
      were the most frequent repeat of dinucleotide SSRs. Flanking primer pairs were
      designed in-silico for the SSR containing sequences. Functional categorization of
      SSRs containing sequences was done through gene ontology terms like biological
      process, cellular component and molecular function.

PMID- 22368383
TI  - In silico modeling of ligand molecule for non structural 3 (NS3) protein target
      of flaviviruses.
AB  - Flaviviruses are small, enveloped RNA viruses which cause a variety of diseases
      into animals and man. Despite the existence of licensed vaccines, yellow fever,
      Japanese encephalitis and tick-borne encephalitis also claim many thousands of
      victims each year across their vast endemic areas. A number of studies have
      already revealed that the non-structural NS3 serine protease is required for the
      maturation of the viral polyprotein and thus is a promising target for the
      development of antiviral inhibitors. Hence, the 3D structure of NS3 protein was
      modeled using homology modeling by MODELLER 9v7. Validation of the constructed
      NS3 protein models were done by PROCHECK, VERYFY3D and through ProSA
      calculations. Ligands for the catalytic triad (H51, D75, and S135) were designed
      using LIGBUILDER. The NS3 protein's catalytic triad was explored to find out the
      interactions pattern for inhibitor binding using molecular docking methodology
      using AUTODOCK Vina. The interactions of complex NS3protein-ligand conformations,
      including hydrogen bonds and the bond lengths were analyzed using Accelrys DS
      Visualizer software. Hence, from this observation, the novel molecule designed
      was observed to be the best ligand against the NS3 protein of flavivirus. This
      molecule may prove to be a potential identity in modulating disease manifestation
      for all the selected flavivirus members. ABBREVIATIONS: NCBI - National Centre
      for Biotechnological Information, BLAST - Basic Local Alignment Search Tool, DOPE
      - Discrete optimized protein energy, GROMOS96 - GROningen MOlecular Simulation
      package, SAVS - Structure Analysis and Validation Server.

PMID- 22368384
TI  - Docking of human rhodopsin mutant (Gly90->Asp) with beta-arrestin and cyanidin 3
      rutinoside to cure night blindness.
AB  - MOTIVATION: Rhodopsin is a visual pigment present in rod cells of retina. It
      belongs to GPCR family and involves photoisomerization of 11-cis-retinal to all
      trans-retinal isomers, conformational changes in rhodopsin and signal
      transduction cascade to generate a nerve impulse. This signaling pathway has been
      targeted to eliminate the effect of a mutation (Gly90->Asp) responsible for
      abnormal activation of G-protein without retinal conformations in the absence of
      light leading to congenital night blindness. A theoretical model of rhodopsin
      with induced mutation has been deliberated in order to find potential ligands
      which can offset this mutational effect. The binding interactions between the
      target mutated rhodopsin model and potential ligands have been predicted with the
      help of molecular docking. The results indicated strong functional benefits of
      ligands as an inhibitor and an agonist for mutated rhodopsin model. Therefore, we
      propose a new visual cascade model which can initiate the normal signaling of
      rhodopsin mutant with the help of proposed ligands and can provide a hope for
      vision in future.

PMID- 22368385
TI  - Metabolic pathway analysis and molecular docking analysis for identification of
      putative drug targets in Toxoplasma gondii: novel approach.
AB  - Toxoplasma gondii is an obligate intracellular apicomplexan parasite that can
      infect a wide range of warm-blooded animals including humans. In humans and other
      intermediate hosts, toxoplasma develops into chronic infection that cannot be
      eliminated by host's immune response or by currently used drugs. In most cases,
      chronic infections are largely asymptomatic unless the host becomes immune
      compromised. Thus, toxoplasma is a global health problem and the situation has
      become more precarious due to the advent of HIV infections and poor toleration of
      drugs used to treat toxoplasma infection, having severe side effects and also
      resistance have been developed to the current generation of drugs. The emergence
      of these drug resistant varieties of T. gondii has led to a search for novel drug
      targets. We have performed a comparative analysis of metabolic pathways of the
      host Homo sapiens and the pathogen T. gondii. The enzymes in the unique pathways
      of T. gondii, which do not show similarity to any protein from the host,
      represent attractive potential drug targets. We have listed out 11 such potential
      drug targets which are playing some important work in more than one pathway. Out
      of these, one important target is Glutamate dehydrogenase enzyme; it plays
      crucial part in oxidation reduction, metabolic process and amino acid metabolic
      process. As this is also present in the targets of tropical diseases of TDR
      (Tropical disease related Drug) target database and no PDB and MODBASE 3D
      structural model is available, homology models for Glutamate dehydrogenase enzyme
      were generated using MODELLER9v6. The model was further explored for the
      molecular dynamics simulation study with GROMACS, virtual screening and docking
      studies with suitable inhibitors against the NCI diversity subset molecules from
      ZINC database, by using AutoDock-Vina. The best ten docking solutions were
      selected (ZINC01690699, ZINC17465979, ZINC17465983, ZINC18141294_03,
      ZINC05462670, ZINC01572309, ZINC18055497_01, ZINC18141294, ZINC05462674 and
      ZINC13152284_01). Further the Complexes were analyzed through LIGPLOT. On the
      basis of Complex scoring and binding ability it is deciphered that these NCI
      diversity set II compounds, specifically ZINC01690699 (as it has minimum energy
      score and one of the highest number of interactions with the active site
      residue), could be promising inhibitors for T. gondii using Glutamate
      dehydrogenase as Drug target.

PMID- 22368386
TI  - Classification and comparative analysis of Curcuma longa L. expressed sequences
      tags (ESTs) encoding glycine-rich proteins (GRPs).
AB  - Glycine-rich proteins (GRPs) are a group of proteins characterized by their high
      content of glycine residues often occurring in repetitive blocs. The diverse
      expression pattern and sub cellular localization of various GRPs suggest their
      implication in different physiological processes. Several GRPs has been isolated
      and characterized from different monocots and dicots. However, little or no
      information is available about the structure and function of GRPs in asexually
      reproducing plants. In this study, in-silico analysis of expressed sequence tag
      database resulted in the isolation of fifty-one GRPs from Curcuma longa L., an
      asexually reproducible plant of great medicinal and economic significance.
      Phylogenetic analysis grouped the GRPs into four distinct classes based on
      conserved motifs and nature of glycine-rich repeats. Majority of the isolated
      GRPs exhibited high homology with known GRPs from other plants that are expressed
      in response to various stresses. The presence of high structural diversity and
      signal peptide in some GRPs suggest their diverse physiological role and tissue
      specific localization. The isolated sequences can be used as a framework for
      cloning, characterization and expressional analysis of GRPs in response to
      various biotic and abiotic stresses in Curcuma longa as well as other asexually
      reproducing plants.

PMID- 22368387
TI  - Evaluation of data integration strategies based on kernel method of clinical and
      microarray data.
AB  - The cancer classification problem is one of the most challenging problems in
      bioinformatics. The data provided by Netherland Cancer Institute consists of 295
      breast cancer patient; 101 patients are with distant metastases and 194 patients
      are without distant metastases. Combination of features sets based on kernel
      method to classify the patient who are with or without distant metastases will be
      investigated. The single data set will be compared with three data integration
      strategies and also weighted data integration strategies based on kernel method.
      Least Square Support Vector Machine (LS-SVM) is chosen as the classifier because
      it can handle very high dimensional features, for instance, microarray data. The
      experiment result shows that the performance of weighted late integration and the
      using of only microarray data are almost similar. The data integration strategy
      is not always better than using single data set in this case. The performance of
      classification absolutely depends on the features that are used to represent the
      object.

PMID- 22368388
TI  - Construction of phosphomannose isomerase (PMI) transformation vectors and
      evaluation of the effectiveness of vectors in tobacco (Nicotiana tabacum L).
AB  - Phosphomannose isomerase (pmi) gene isolated from Escherichia coli allows
      transgenic plants carrying it to convert mannose-6- phosphate (from mannose), a
      carbon source that could not be naturally utilized by plants into fructose-6
      phosphate which can be utilized by plants as a carbon source. This conversion
      ability provides energy source to allow the transformed cells to survive on the
      medium containing mannose. In this study, four transformation vectors carrying
      the pmi gene alone or in combination with the beta-glucuronidase (gusA) gene were
      constructed and driven by either the maize ubiquitin (Ubi1) or the cauliflower
      mosaic virus (CaMV35S) promoter. Restriction digestion, PCR amplification and
      sequencing were carried out to ensure sequence integrity and orientation. Tobacco
      was used as a model system to study the effectiveness of the constructs and
      selection system. PMI11G and pMI3G, which carry gusA gene, were used to study the
      gene transient expression in tobacco. PMI3 construct, which only carries the pmi
      gene driven by CaMV35S promoter, was stably transformed into tobacco using
      biolistics after selection on 30 g 1(-1) mannose without sucrose. Transgenic
      plants were verified using PCR analysis. ABBREVIATIONS: PMI/pmi - Phosphomannose
      isomerase, Ubi1 - Maize ubiquitin promoter, CaMV35S - Cauliflower mosaic virus
      35S promoter, gusA - beta-glucuronidase GUS reporter gene.

PMID- 22368389
TI  - Codon usage bias as a function of generation time and life expectancy.
AB  - It has recently been demonstrated that human natural codon usage bias is
      optimized towards a higher buffering capacity to mutations (measured as the
      tendency of single point mutations in a DNA sequence to yield the same or similar
      amino acids) compared to random sequences. In this work, we investigate this
      phenomenon further by analyzing the natural DNA of four different species (human,
      mouse, zebrafish and fruit fly) to determine whether such a tolerance to
      mutations is correlated with the life span and age of sexual maturation for the
      corresponding organisms. We also propose a new measure to quantify the buffering
      capacity of a DNA sequence to mutations that takes into account the observed
      mutation rates within every genome and the effect of the corresponding
      mutation.Our results suggest there is a propensity for tolerance to mutations
      that is positively correlated with the life expectancy of the considered
      organisms. Moreover, random sequences that are constrained to produce the same
      protein as the naturally occurring sequences are found to be more buffered than
      completely random sequences while being less buffered than the natural sequences.
      These results suggest that optimization toward protective mechanisms tolerant to
      mutations is correlated with both life expectancy and age to sexual maturity at
      both the levels of codon usage bias and the bias of the natural sequence of
      codons itself.

PMID- 22368390
TI  - Schematic for efficient computation of GC, GC3, and AT3 bias spectra of genome.
AB  - Selection of synonymous codons for an amino acid is biased in protein translation
      process. This biased selection causes repetition of synonymous codons in
      structural parts of genome that stands for high N/3 peaks in DNA spectrum. Period
      3 spectral property is utilized here to produce a 3-phase network model based on
      polyphase filterbank concepts for derivation of codon bias spectra (CBS).
      Modification of parameters in this model can produce GC, GC3, and AT3 bias
      spectra. Complete schematic in LabVIEW platform is presented here for efficient
      and parallel computation of GC, GC3, and AT3 bias spectra of genomes alongwith
      results of CBS patterns. We have performed the correlation coefficient analysis
      of GC, GC3, and AT3 bias spectra with codon bias patterns of CBS for biological
      and statistical significance of this model.

PMID- 22368391
TI  - ProPAS: standalone software to analyze protein properties.
AB  - Physicochemical properties of proteins/peptides are often used to separate
      proteins/peptides from complex biological samples in proteomics research, which
      is necessary for the further proteins/peptides identification. So, the analyses
      of these properties are very important for the design of proteomic experiments
      and the further analyses of identified results. Current available web-based tools
      are difficult to analyze large-scale datasets. Here we provide a standalone
      software ProPAS (Protein Properties Analyses Software) to calculate these
      properties in local computers. ProPAS could be used to calculate several
      physicochemical parameters of proteins/peptides, including the isoelectric point
      (pI), hydrophobicity (Hy) and mass weight (MW). Additionally, ProPAS provides the
      statistic results to get the number distribution along the parameter values. The
      results could be copied to other software such as Excel to get the distribution
      chart. The amino acid composition of all the input proteins/peptides could also
      be calculated from all input sequences. Detail description, updates and download
      link for ProPAS could be found at the website of
      http://bioinfo.hupo.org.cn/tools/ProPAS/propas.htm.

PMID- 22368392
TI  - Journal of Pharmacy and BioAllied Sciences Vol 4 Issue 1.

PMID- 22368393
TI  - Status of surfactants as penetration enhancers in transdermal drug delivery.
AB  - Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical
      preparations. In recent years, surfactants have been employed to enhance the
      permeation rates of several drugs via transdermal route. The application of
      transdermal route to a wider range of drugs is limited due to significant barrier
      to penetration across the skin which is associated with the outermost stratum
      corneum layer. Surfactants have effects on the permeability characteristics of
      several biological membranes including skin. They have the potential to
      solubilize lipids within the stratum corneum. The penetration of the surfactant
      molecule into the lipid lamellae of the stratum corneum is strongly dependent on
      the partitioning behavior and solubility of surfactant. Surfactants ranging from
      hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have
      been tested as permeation enhancer to improve drug delivery. This article reviews
      the status of surfactants as permeation enhancer in transdermal drug delivery of
      various drugs.

PMID- 22368394
TI  - Current approaches toward production of secondary plant metabolites.
AB  - Plants are the tremendous source for the discovery of new products with medicinal
      importance in drug development. Today several distinct chemicals derived from
      plants are important drugs, which are currently used in one or more countries in
      the world. Secondary metabolites are economically important as drugs, flavor and
      fragrances, dye and pigments, pesticides, and food additives. Many of the drugs
      sold today are simple synthetic modifications or copies of the naturally obtained
      substances. The evolving commercial importance of secondary metabolites has in
      recent years resulted in a great interest in secondary metabolism, particularly
      in the possibility of altering the production of bioactive plant metabolites by
      means of tissue culture technology. Plant cell and tissue culture technologies
      can be established routinely under sterile conditions from explants, such as
      plant leaves, stems, roots, and meristems for both the ways for multiplication
      and extraction of secondary metabolites. In vitro production of secondary
      metabolite in plant cell suspension cultures has been reported from various
      medicinal plants, and bioreactors are the key step for their commercial
      production. Based on this lime light, the present review is aimed to cover
      phytotherapeutic application and recent advancement for the production of some
      important plant pharmaceuticals.

PMID- 22368395
TI  - Application of microarray in breast cancer: An overview.
AB  - There are more than 1.15 million cases of breast cancer diagnosed worldwide
      annually. At present, only small numbers of accurate prognostic and predictive
      factors are used clinically for managing the patients with breast cancer. DNA
      microarrays have the potential to assess the expression of thousands of genes
      simultaneously. Recent preliminary researches indicate that gene expression
      profiling based on DNA microarray can offer potential and independent prognostic
      information in patients with newly diagnosed breast cancer. In this paper, an
      overview upon the applications of microarray techniques in breast cancer is
      presented.

PMID- 22368397
TI  - Structure-based design, synthesis, molecular docking, and biological activities
      of 2-(3-benzoylphenyl) propanoic acid derivatives as dual mechanism drugs.
AB  - PURPOSE: 2-(3-benzoyl phenyl)propanohydroxamic acid (2) and 2-{3
      [(hydroxyimino)(phenyl)methyl]phenyl}propanoic acid (3) were synthesized from non
      steroidal anti-inflammatory drug, ketoprofen as dual-mechanism drugs. MATERIALS
      AND METHODS: Structures of the synthesized compounds were established by IR, (1)H
      NMR, and mass spectroscopy. Both compounds were screened for their anti
      inflammatory activity in rat paw edema model and in vitro antitumor activity
      against 60 human tumor cell lines. Flexible ligand docking studies were performed
      with different matrix metalloproteinases and cyclooxygenases to gain an insight
      into the structural preferences for their inhibition. RESULTS: Compound (2)
      proved out to be more potent than ketoprofen in rat paw edema model. Both
      compounds showed moderate anticancer activity ranging from 1% to 23% inhibition
      of growth in 38 cell lines of 8 tumor subpanels at 10 MUM concentration in a
      single dose experiment. Hydroxamic acid analogue was found to be more potent than
      ketoximic analogue in terms of its antitumor activity. CONCLUSION: Analysis of
      docking results together with experimental findings provide a good explanation
      for the biological activities associated with synthesized compounds which may be
      fruitful in designing dual-target-directed drugs that may inhibit cyclooxygenases
      and MMPs for the treatment of cancer.

PMID- 22368398
TI  - Clinico-pathological correlates of incidentally revealed thyroid swelling in
      Bihar, India.
AB  - BACKGROUND: Global prevalence of thyroid cancer has been on the rise in recent
      decades. OBJECTIVES: To study the clinical presentations to reach an agreement
      for diagnosis and optimal management of incidentally revealed thyroid swellings
      for early diagnosis. MATERIALS AND METHODS: A prospective study was carried out
      on 178 cases of incidentally detected thyroid swelling attending a tertiary care
      teaching institute of Kishanganj Bihar. All the cases were subjected to a
      thorough clinical examination followed by evidence-based interventions. Fine
      needle aspiration cytology was done in all the cases preoperatively as out
      patients basis and histopathologically confirmed postoperatively. RESULTS: The
      highest incidence of thyroid swelling (75.84%) was found in the age group of 20
      40 years; a female preponderance was noted in the ratio 4:1. The duration of
      swelling ranged from six months to three years. Difficulty in swallowing and
      breathing was complained by 23 (12.9%) and 18 (10.1%) of the patients
      respectively. Typically the swellings were located in the right lobe. Commonly
      the subjects in our study were in euthyroid state (90%) and were with firm
      swellings (66.7%). Follicular and anaplastic carcinoma was important
      postoperative cytological findings. Majority of surgical intervention was
      hemithyroidectomy (55.06%). CONCLUSION: Incidentally revealed thyroid swelling
      was quite high in eastern India for which we need a consensus line of
      intervention.

PMID- 22368399
TI  - In silico study of fucoxanthin as a tumor cytotoxic agent.
AB  - BACKGROUND: Fucoxanthin is a potential tumor cytotoxic compound. However,
      mechanisms underlying the activities are unclear. AIM: This in silico study aimed
      to predict the main mechanism of fucoxanthin; whether with its binding to p53
      gene, CDK2, or tubulin. MATERIALS AND METHODS: In silico was studied by using
      Autodock-Vina's algorithms. The mechanisms being analyzed by comparison of
      fucoxanthin and native ligands binding energies in p53 gene (1RV1), CDK2 (1AQ1),
      and three binding sites of tubulin (1JFF-paclitaxel, 1SA0-colchicine, and 1Z2B
      vinblastine site). RESULTS: Autodock-Vina's algorithms were valid, as re-docking
      the native ligands to their receptors showed a RSMD value less than 2 A with
      binding energies of -11.5 (1RV1), -14.4 (1AQ1), -15.4 (1JFF), -9.2 (1SA0), and 
      9.7 (1Z2B) kcal/mol. Docking of fucoxanthin to subjected receptors were -6.2
      (1RV1), -9.3 (1AQ1), -8.1 (1JFF), -9.2 (1SA0), and -7.2 (1Z2B) kcal/mol. Virtual
      analysis of fucoxanthin and tubulin binding structure showed the carboxyl moiety
      in fucoxanthin make a hydrogen bound with 355Val (2.61 A) and 354Ala (2.79 A) at
      tubulin. CONCLUSION: The results showed that binding energy of fucoxanthin could
      only reach the same level as with colchicine ligand in tubulin. Therefore, it may
      predict that the most probable fucoxanthin main mechanism is to bind tubulin,
      which causes microtubules depolimerization and cell cycle arrest.

PMID- 22368400
TI  - Protective effect of Emilia sonchifolia (L.) against high protein diet induced
      oxidative stress in pancreas of Wistar rats.
AB  - OBJECTIVES: The present study was undertaken to investigate the oxidative damage,
      the biochemical and histopathological changes in the pancreas of the Wistar rats
      which was fed high protein diet and the recovery after the oral administration of
      the n-hexane extract of the herb, Emilia sonchifolia. MATERIALS AND METHODS: The
      rats fed with high protein diet for a period of 30 days and treated with n-hexane
      extract of Emilia sonchifolia (250 mg/kg body weight). Body weight, pancreatic
      weight, serum amylase, lipase, aspartate transaminase, alanine transaminase,
      urea, uric acid, creatinine, DNA and RNA content of the pancreas, pancreatic
      enzymatic and non-enzymatic antioxidants such as superoxide dismutase, catalase,
      glutathione peroxidase, reduced glutathione, and vitamin C were evaluated.
      RESULTS AND DISCUSSION: At the end of the study the rats gained less body weight
      and showed a significant (P < 0.05) increase in serum levels of amylase, lipase,
      aspartate transaminase, alanine transaminase, urea, uric acid, creatinine, tissue
      DNA, and RNA content and showed a significant (P < 0.05) decrease in the
      pancreatic antioxidants. Treatment with the n-hexane extract ameliorated the
      damage caused by high protein diet. This was also evidenced by histopathological
      studies. CONCLUSION: From the results, it was suggested that the n-hexane extract
      of Emilia sonchifolia has an effective medicinal property and can act as a
      pancreato-protective herb.

PMID- 22368396
TI  - A pharmacological appraisal of medicinal plants with antidiabetic potential.
AB  - Diabetes mellitus is a complicated metabolic disorder that has gravely troubled
      the human health and quality of life. Conventional agents are being used to
      control diabetes along with lifestyle management. However, they are not entirely
      effective and no one has ever been reported to have fully recovered from
      diabetes. Numerous medicinal plants have been used for the management of diabetes
      mellitus in various traditional systems of medicine worldwide as they are a great
      source of biological constituents and many of them are known to be effective
      against diabetes. Medicinal plants with antihyperglycemic activities are being
      more desired, owing to lesser side-effects and low cost. This review focuses on
      the various plants that have been reported to be effective in diabetes. A record
      of various medicinal plants with their established antidiabetic and other health
      benefits has been reported. These include Allium sativa, Eugenia jambolana, Panax
      ginseng, Gymnema sylvestre, Momrodica charantia, Ocimum sanctum, Phyllanthus
      amarus, Pterocarpus marsupium, Trigonella foenum graecum and Tinospora
      cordifolia. All of them have shown a certain degree of antidiabetic activity by
      different mechanisms of action.

PMID- 22368402
TI  - Antiplasmodial activity of bacilosarcin A isolated from the octocoral-associated
      bacterium Bacillus sp. collected in Panama.
AB  - AIM: This study was designed for isolating and characterizing antiplasmodial
      compounds from marine octocoral-associated bacteria. MATERIALS AND METHODS: The
      organic extract of the Bacillus sp. was subjected to purification using several
      chromatography techniques guided by bioassays to yield three isocoumarin
      derivatives (1-3). Chemical structures of the compounds were elucidated on the
      basis of HRMS spectra and NMR spectroscopy. The antiplasmodial activity of the
      isolated compounds was evaluated in vitro against the chloroquine-resistant
      Plasmodium falciparum strain W2. RESULTS: Isolated compounds were identified as
      bacilosarcin A (1), AI77-F (2), and AI77-H (3). Bacilosarcin A (1) displayed a
      low micromolar activity (IC(50) = 2.2 MUM) against P. falciparum while compounds
      2 and 3 showed no activity. CONCLUSIONS: Bacilosarcin A was found to be
      responsible for the antiplasmodial activity observed in the crude extract
      obtained from the Bacillus sp.

PMID- 22368403
TI  - Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery
      occluded rat.
AB  - PURPOSE: Aqueous and hydroalcoholic extracts of Nigella sativa (400 mg/kg,
      orally) for 7 days were administered and evaluated for their neuroprotective
      effects on middle cerebral artery occluded (MCAO) rats. MATERIALS AND METHODS:
      Cerebral ischemia was induced by middle cerebral artery occlusion for 2 h
      followed by reperfusion for 22 h. After 24 h of ischemia, grip strength,
      locomotor activity tests were performed in the surgically operated animals. After
      behavioral tests, animals were immediately sacrificed. Infarct volumes followed
      by the estimation of markers of oxidative stress in the brains were measured.
      RESULTS: Locomotor activity and grip strength of animals were improved in both
      aqueous and hydroalcoholic extracts pretreated rats. Infarct volume was also
      reduced in both extracts pretreated rats as compared with MCAO rats. An elevation
      of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione
      and antioxidant enzymes, viz., superoxide dismutase (SOD) and catalase levels
      were observed following MCAO. Pretreatment of Nigella sativa extracts showed the
      reduction in TBARS, elevation in glutathione, SOD and catalase levels as compared
      with MCAO rats. CONCLUSION: The present study observed the neuroprotective
      effects of both the extracts of Nigella sativa in cerebral ischemia. The
      neuroprotective effects could be due to its antioxidant, free radical scavenging,
      and anti-inflammatory properties.

PMID- 22368405
TI  - Stem cells: Challenges in endodontics.

PMID- 22368404
TI  - Cardiac antiapoptotic and proproliferative effect of recombinant human
      erythropoietin in a moderate stage of chronic renal failure in the rat.
AB  - OBJECTIVE: Recombinant human erythropoietin (rhEPO) therapy under circumstances
      of moderate chronic renal failure (CRF), with yet lower kidney and heart lesion,
      may have a protective cardiac effect beyond the correction of anemia, whose
      mechanism deserves better elucidation, namely by clarifying the impact on gene
      expression profile of markers of apoptosis, inflammation, proliferation,
      angiogenesis, and lesion/stress in the heart. MATERIALS AND METHODS: Four groups
      of rats were studied over a period of 15 weeks (n=7 each): control-without
      surgery and without drug treatment; rhEPO-treated with 50 IU/kg/week of rhEPO
      beta; CRF-submitted to partial nephrectomy (3/4); CRF + rhEPO-CRF with rhEPO
      treatment after the 3rd week of surgery. The heart was collected in order to
      evaluate the gene expression, by real-time qPCR, of markers of apoptotic
      machinery, inflammation/immunology, proliferation/angiogenesis, and
      lesion/stress. RESULTS: The main findings obtained were (a) CRF rats have
      demonstrated overexpression of EPO-R in the heart without changes on EPO
      expression, together with overexpression of Bax/Bcl2 ratio, PCNA, and IL-2; (b)
      rhEPO therapy on the heart of the rats with CRF induced by partial 3/4
      nephrectomy promoted nonhematopoietic protection, demonstrated by the apoptosis
      prevention, viewed by the Bax/Bcl2 balance, by the promotion of proliferation,
      due to PCNA increment, and by the immunomodulatory action, expressed by a trend
      to prevent the IL-2 increment. CONCLUSION: In this model of moderate CRF, rhEPO
      treatment showed important cardiac nonhematopoietic effects, expressed mainly by
      the antiapoptotic and the proproliferative action, suggesting that early rhEPO
      therapy in moderate stages of CRF might have further therapeutic benefits.

PMID- 22368406
TI  - Pharm D: A new concept in India.

PMID- 22368407
TI  - Calling a spade a spade... why editors are uncomfortable to say it as it is.

PMID- 22368408
TI  - Phenylpropanolamine and the hemorrhagic stroke: A new search for the culprit.

PMID- 22368409
TI  - How full is our antihypertensives pipeline?

PMID- 22368410
TI  - Iptakalim: A novel multi-utility potassium channel opener.

PMID- 22368411
TI  - A urinalysis-based study of buprenorphine and non-prescription opioid use among
      patients on buprenorphine maintenance.
AB  - OBJECTIVES: To understand the pattern of use of opioid-substitution therapy (OST)
      and opioid abuse among patients on buprenorphine maintenance using urinalysis.
      MATERIALS AND METHODS: The study was conducted at a tertiary care de-addiction
      center. We reviewed the laboratory record of all consecutive urine samples sent
      for drug analysis over a period of 1 year. In all, 179 consecutive urine samples
      were included in the analysis. The chi-square test was used to compare opioid
      abuse among those testing positive and negative for buprenorphine on urinalysis.
      Additionally, in order to assess the potential impact of the prescribed induction
      and maximum dose of buprenorphine on the findings, we carried out the independent
      samples t test. Level of statistical significance was kept at P<0.05 for all the
      tests. RESULTS: Urinalysis failed to detect buprenorphine in 44.7% of the
      samples. Rate of detection of dextropropoxyphene was significantly higher among
      buprenorphine-negative samples (P<0.005). The prescribed induction dose of
      buprenorphine was significantly lower among those testing positive for heroin.
      This was found for both buprenorphine-positive (P<0.005) as well as buprenorphine
      negative samples (P<0.005). CONCLUSIONS: These findings support the routine use
      of urine drug screening among individuals on OST.

PMID- 22368412
TI  - Secondary metabolites of Cynodon dactylon as an antagonist to angiotensin II
      type1 receptor: Novel in silico drug targeting approach for diabetic retinopathy.
AB  - OBJECTIVES: To study the ability of the secondary metabolites of Cynodon dactylon
      to serve as an antagonist to angiotensin II type 1 receptor (AT(1)); activation
      of this receptor plays a vital role in diabetic retinopathy (DR). MATERIALS AND
      METHODS: In silico methods are mainly harnessed to reduce time, cost and risk
      associated with drug discovery. Twenty-four compounds were identified as the
      secondary metabolites of hydroalcoholic extract of C. dactylon using the GCMS
      technique. These were considered as the ligands or inhibitors that would serve as
      an antagonist to the AT(1). The ACD/Chemsketch tool was used to generate 3D
      structures of the ligands. A molecular file format converter tool was used to
      convert the generated data to the PDB format (Protein Data Bank) and was used for
      docking studies. The AT(1) structure was retrieved from the Swissprot data base
      and PDB and visualized using the Rasmol tool. Domain analysis was carried from
      the Pfam data base; following this, the active site of the target protein was
      identified using a Q-site finder tool. The ability of the ligands to bind with
      the active site of AT(1) was studied using the Autodocking tool. The docking
      results were analyzed using the WebLab viewer tool. RESULTS: Sixteen ligands
      showed effective binding with the target protein; diazoprogesteron, didodecyl
      phthalate, and 9,12-octadecadienoyl chloride (z,z) may be considered as compounds
      that could be used to bind with the active site sequence of AT(1). CONCLUSIONS:
      The present study shows that the metabolites of C. dactylon could serve as a
      natural antagonist to AT(1) that could be used to treat diabetic retinopathy.

PMID- 22368413
TI  - Antiproliferative property of n-hexane and chloroform extracts of Anisomeles
      malabarica (L). R. Br. in HPV16-positive human cervical cancer cells.
AB  - OBJECTIVES: To find the efficacy of serial extracts of Anisomeles malabarica in
      inhibiting proliferation of and inducing apoptosis in human cervical cancer
      cells, SiHa and ME 180, that are HPV 16-positive. MATERIALS AND METHODS: The
      whole plant was extracted in n-hexane, chloroform, ethyl acetate, n-butanol,
      methanol, and water. The cells were treated with the extracts at increasing
      concentrations to find the IC(50), adopting MTT ([3-(4,5 dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide]) assay. Acridine orange (AO) and ethidium
      bromide (EB) and Hoechst 33258 staining were adopted to assess the mode of cell
      death, Annexin V-Cy3 staining to evaluate one of the early apoptotic features, JC
      1 staining to assess the mitochondrial membrane depolarization, comet assay for
      DNA fragmentation, and cell cycle analysis for the distribution of cells after
      treatment. RESULTS: n-Hexane and chloroform extracts were cytotoxic to the
      cervical cancer cells in dose- and duration-dependent manner. The cells that
      responded to the treatments revealed typical apoptotic features. Early features
      of apoptosis, phosphatidyl serine translocation and loss of mitochondrial trans
      membrane potential, were observed in the treated cells, and comet assay revealed
      DNA damage. In the FACS analysis, the cells accumulated in the sub-G0/G1 phase of
      the cell cycle, except in n-hexane- and chloroform extract-treated SiHa cells at
      24 h, which showed arrest in S- and G2/M phases. CONCLUSIONS: n-Hexane and
      chloroform extracts of A. malabarica inhibit proliferation of and induce death in
      HPV16-positive cervical cancer cells, mostly by apoptosis and to some extent by
      necrosis.

PMID- 22368414
TI  - Analysis of hematinic formulations available in the Indian market.
AB  - OBJECTIVES: To analyze the hematinic formulations available in Indian market for
      their varieties of dosage forms, iron salts used, content of elemental iron,
      frequency of administration, additional nutrients, and cost. MATERIALS AND
      METHODS: Hematinic formulations listed in Indian Drug Review (2009) were analyzed
      for the iron salts contained and the elemental iron content. Preparations
      containing iron +/- folic acid +/- vitamin C were considered as 'acceptable'
      formulations. For proper comparison, cost of 100 mg elemental iron in each
      formulation was calculated. Acceptable oral formulations containing iron with
      folic acid were further classified according to iron salts, and the median cost
      of various iron salts was compared. We also identified oral solid formulations
      that required administration more than three times a day. Prices of 'acceptable'
      iron preparations were compared with that of 'irrational' formulations. RESULTS:
      Out of 621 formulations, 365 were oral solid formulations, 232 were oral liquids,
      and 24 were for parenteral administration. Formulations containing iron salts
      like ferrous sulphate, ferrous sulphate (dried), carbonyl iron, and ferrous
      fumarate are cheaper than formulations containing other iron salts. Among the 365
      oral (solid) iron formulations, we found 60 that would require administration
      more than three times a day to provide a therapeutic dosage of elemental iron. As
      compared to irrational formulations, the cost of acceptable formulations was in a
      significantly narrow range; however, the median cost of acceptable products was
      significantly higher than that of the irrational ones, except in case of the
      parenteral preparations. CONCLUSION: The drug regulation authorities should tune
      the drug price in such a way that rational formulations cost less than the
      irrational ones.

PMID- 22368415
TI  - Acute effects of granulocyte colony-stimulating factor on early ventricular
      arrhythmias after coronary occlusion in rats.
AB  - OBJECTIVES: To evaluate the acute effects of colony-stimulating factor (G-CSF) on
      ventricular arrhythmias after coronary occlusion in rats. MATERIALS AND METHODS:
      Male Wistar rats (10 weeks) received G-CSF (100 MUg.kg(-1)) or vehicle. Thirty
      minutes later, animals were infarcted by coronary occlusion under artificial
      respiration. Electrocardiogram was monitored for 30 min to evaluate ventricular
      arrhythmias. RESULTS: G-CSF treatment reduced the number of premature ventricular
      beats and the number and duration of ventricular tachycardia. The incidence of
      ventricular fibrillation was significantly reduced by G-CSF (MI-Cont: 11.2 +/-
      2.4 vs. MI-GCSF: 5.4 +/- 1 events; P < 0.05). However, total duration of
      ventricular fibrillation was not altered (MI-Cont: 84 +/- 16 vs. MI-GCSF: 76 +/-
      13 sec). CONCLUSIONS: Acute administration of G-CSF before coronary ligature in
      rats reduces the incidence of ventricular premature beats and ventricular
      tachycardia, suggesting a possible direct electrophysiological effect of this
      cytokine independently of its genomic effects. However, the data suggest that G
      CSF treatment may affect the spontaneous recovery from ventricular fibrillation.
      Acute G-CSF administration acts directly on cardiac electrophysiology, different
      from chronic treatment.

PMID- 22368416
TI  - Evaluation of the aphrodisiac activity of Tribulus terrestris Linn. in sexually
      sluggish male albino rats.
AB  - OBJECTIVES: To study the effect of acute and repeated dose administration of
      lyophilized aqueous extract of the dried fruits of Tribulus terrestris (LAET) on
      sexual function in sexually sluggish male albino rats. MATERIALS AND METHODS:
      Aphrodisiac activity of the test drug was evaluated in terms of exhibited sexual
      behavior. In order to assess the effect of chronic T. terrestris exposure on the
      hypothalamus--pituitary--gonadal axis, testosterone level estimation and sperm
      count were carried out. Twenty-eight-day oral toxicity studies were carried out
      to evaluate the long-term effects of the LAET administration on different body
      systems. RESULTS: A dose-dependent improvement in sexual behavior was observed
      with the LAET treatment as characterized by an increase in mount frequency,
      intromission frequency, and penile erection index, as well as a decrease in mount
      latency, intromission latency, and ejaculatory latency. The enhancement of sexual
      behavior was more prominent on chronic administration of LAET. Chronic
      administration of LAET produced a significant increase in serum testosterone
      levels with no significant effect on the sperm count. No overt body system
      dysfunctions were observed in 28-day oral toxicity study. CONCLUSIONS: Findings
      of the present study validate the traditional use of T. terrestris as a sexual
      enhancer in the management of sexual dysfunction in males.

PMID- 22368417
TI  - A randomized comparative study of safety and efficacy of immediate release
      glucosamine HCL and glucosamine HCL sustained release formulation in the
      treatment of knee osteoarthritis: A proof of concept study.
AB  - OBJECTIVES: To compare the safety and efficacy of glucosamine HCl- sustained
      release (GLU-SR) with that of Glucosamine HCl- immediate release (GLU-IR) in
      patients with knee osteoarthritis (OA). MATERIALS AND METHODS: This study
      involved 59 patients with knee OA, randomised to receive single oral dose of
      1,500 mg, GLU-SR and GLU-IR for 60 days with 31 and 28 patients, respectively.
      The primary efficacy (pain and function) was assessed using visual analogue scale
      (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      scores. Intention-to-treat principle, repeated measure of ANOVA and mixed model
      analysis were used. RESULTS: The patients baseline, demographic and clinical
      characteristics were comparable between groups with female preponderance
      (71.20%). There was a significant reduction in algofunctional indices as primary
      outcome measure in both the groups across time (P < 0.001) and 29% lesser adverse
      events (AEs) in GLU-SR group, with no difference in the use of rescue
      medications. CONCLUSIONS: The study showed equal efficacy of the glucosamine
      formulations on algofunctional indices in reducing pain in patients with knee OA
      with less number of AEs in GLU-SR.

PMID- 22368418
TI  - Gender and racial bias in drug promotional material distributed by pharmaceutical
      companies.

PMID- 22368419
TI  - Interns opinion on 'bedside pharmacology clinics' and its incorporation in
      undergraduate curriculum.

PMID- 22368420
TI  - Steroids in leptospiral uveitis: Does the route of administration matter?

PMID- 22368421
TI  - Antidepressant-like activity of Benincasa hispida fruits in mice: Possible
      involvement of monoaminergic and GABAergic systems.

PMID- 22368422
TI  - Anticonvulsant activity of Erythrina mysorensis bark extract in an animal model
      of epilepsy.

PMID- 22368423
TI  - Antidiabetic activity of stem bark of Bauhinia variegata in alloxan-induced
      hyperglycemic rats.

PMID- 22368424
TI  - Wound healing activity of Hemidesmus indicus formulation.

PMID- 22368425
TI  - Non-occlusive mesenteric ischemia and the role of cilostazol in its management.
AB  - Bowel ischemia is a rare and potential life-threatening disorder. The reason for
      its rarity is the difficulty in its diagnosis. Vague and nonspecific clinical
      findings and limitations of diagnostic and treatment options make this disease a
      significant challenge. We hereby report two cases of non-occlusive mesenteric
      ischemia and the use of cilostazol in the successful management of such cases.

PMID- 22368426
TI  - Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent
      seizures and acute encephalopathy in a pediatric patient: Possibly due to
      pertussis fraction.
AB  - A 5-month-old male patient developed recurrent seizures and acute encephalopathy
      possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus
      (DPT) vaccine used for routine immunization. Postreaction computed tomography
      (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and
      electroencephalogram were normal. Pertussis fraction of DPT vaccine is
      responsible for this reaction. It is suggested that acellular pertussis vaccine
      should be used instead of whole cell vaccine because it is associated with lower
      frequency of neurological complications, such as seizures, encephalopathy, and
      hypotensive episodes. However, acellular pertussis-containing vaccines are
      currently not affordable in most developing countries.

PMID- 22368427
TI  - An adverse drug reaction clinic: Breathing fresh life into the pharmacovigilance
      programme.

PMID- 22368428
TI  - Assessing citations with Google Scholar: A new feature.

PMID- 22368429
TI  - Revisiting undergraduate practical pharmacology.

PMID- 22368430
TI  - Prophylactic ocular hypotensives before Nd:YAG laser posterior capsulotomy.

PMID- 22368431
TI  - Authors' reply.

PMID- 22368432
TI  - Adverse drug reaction of oseltamivir in pediatric patients.

PMID- 22368433
TI  - Evaluation of the appropriateness of prescribing in geriatric patients using
      Beers' criteria and Phadke's criteria and comparison thereof by Rima Shah and
      colleagues.

PMID- 22368434
TI  - Belatacept: Good, but not good enough?

PMID- 22368435
TI  - Authors' reply.

PMID- 22368436
TI  - The national centre for the replacement, refinement, and reduction of animals in
      research.

PMID- 22368437
TI  - Belatacept: A worthy alternative to cyclosporine?

PMID- 22368438
TI  - Penalized Functional Regression.
AB  - We develop fast fitting methods for generalized functional linear models. The
      functional predictor is projected onto a large number of smooth eigenvectors and
      the coefficient function is estimated using penalized spline regression;
      confidence intervals based on the mixed model framework are obtained. Our method
      can be applied to many functional data designs including functions measured with
      and without error, sparsely or densely sampled. The methods also extend to the
      case of multiple functional predictors or functional predictors with a natural
      multilevel structure. The approach can be implemented using standard mixed
      effects software and is computationally fast. The methodology is motivated by a
      study of white-matter demyelination via diffusion tensor imaging (DTI). The aim
      of this study is to analyze differences between various cerebral white-matter
      tract property measurements of multiple sclerosis (MS) patients and controls.
      While the statistical developments proposed here were motivated by the DTI study,
      the methodology is designed and presented in generality and is applicable to many
      other areas of scientific research. An online appendix provides R implementations
      of all simulations.

PMID- 22368439
TI  - Functional Information: Towards Synthesis of Biosemiotics and Cybernetics.
AB  - Biosemiotics and cybernetics are closely related, yet they are separated by the
      boundary between life and non-life: biosemiotics is focused on living organisms,
      whereas cybernetics is applied mostly to non-living artificial devices. However,
      both classes of systems are agents that perform functions necessary for reaching
      their goals. I propose to shift the focus of biosemiotics from living organisms
      to agents in general, which all belong to a pragmasphere or functional universe.
      Agents should be considered in the context of their hierarchy and origin because
      their semiosis can be inherited or induced by higher-level agents. To preserve
      and disseminate their functions, agents use functional information - a set of
      signs that encode and control their functions. It includes stable memory signs,
      transient messengers, and natural signs. The origin and evolution of functional
      information is discussed in terms of transitions between vegetative, animal, and
      social levels of semiosis, defined by Kull. Vegetative semiosis differs
      substantially from higher levels of semiosis, because signs are recognized and
      interpreted via direct code-based matching and are not associated with ideal
      representations of objects. Thus, I consider a separate classification of signs
      at the vegetative level that includes proto-icons, proto-indexes, and proto
      symbols. Animal and social semiosis are based on classification, and modeling of
      objects, which represent the knowledge of agents about their body (Innenwelt) and
      environment (Umwelt).

PMID- 22368440
TI  - Bilateral choroidal neovascularization associated with optic nerve head drusen
      treated by antivascular endothelial growth factor therapy.
AB  - OBJECTIVE: To report a good clinical outcome in a patient with bilateral
      choroidal neovascularization (CNV) associated with optic nerve head drusen (ONHD)
      treated with intravitreal ranibizumab injection. METHODS: A 12-year-old girl was
      referred for loss of right eye vision detected in a routine check-up. Best
      corrected visual acuity (BCVA) was hand movements in the right eye and 0.9 in the
      left eye. Funduscopy revealed the presence of superficial and buried bilateral
      ONHD, which was confirmed by ultrasonography and computed tomography, and the
      study was completed with perimetry. The presence of bilateral CNV, active in the
      right eye, was observed and subsequently confirmed using fluorescein angiography
      and optical coherence tomography. RESULTS: Treatment with two consecutive
      injections of intravitreal ranibizumab resulted in inactivation of the
      neovascular membrane with subretinal fluid reabsorption and improved right eye
      BCVA. After 12 months' follow-up, this was 20/60 and stable. CONCLUSION: Although
      there are no published studies of safety in children, antiangiogenic therapy for
      CNV secondary to ONHD may be useful and safe. A search of the literature produced
      only one previously reported case of ONHD-associated CNV treated with
      antivascular endothelial growth factor alone.

PMID- 22368441
TI  - Further data on the association between Helicobacter pylori infection and primary
      open-angle glaucoma.

PMID- 22368442
TI  - Reshaping the eyebrow by follicular unit transplantation from excised eyebrow in
      extended infrabrow excision blepharoplasty.
AB  - PURPOSE: We report the reshaping of the eyebrow by follicular unit
      transplantation from excised eyebrow skin in extended infrabrow excision
      blepharoplasty. METHODS: The method was carried out in two patients with moderate
      or significant dermatochalasis. The areas to be excised from the infrabrow and
      intrabrow skin were decided upon and the area of hair transplantation was planned
      in the suprabrow area and the tail of the eyebrow. The skin was removed and the
      excised intrabrow skin was dissected into single follicular units. Tiny incisions
      were made with a scalpel, and grafts were inserted using fine forceps. RESULTS:
      Almost all transplanted eyebrow follicles took successfully, resulting in
      eyebrows of a desirable shape as planned preoperatively. The reshaped eyebrows
      had a natural appearance since the transplanted hairs were similar to those of
      the original eyebrow. The eyelids still looked youthful rather than operated-on.
      Finally, the evidence of blepharoplasty was hardly visible and patient
      satisfaction was quite high. The patients felt more ease in opening their eyes
      and obtained a wider visual field. CONCLUSION: Our study demonstrated excellent
      results with hair transplantation from eyebrow to eyebrow, a finding which, to
      our knowledge, has not been previously reported. Our method can be used for
      selected patients, especially men, with moderate to severe dermatochalasis, who
      find a reduction or change in the shape of the eyebrow unacceptable.

PMID- 22368443
TI  - Lower conjunctival fornix packing for mydriasis in premature infants: a
      randomized trial.
AB  - OBJECTIVE: To compare the mydriatic effect of lower conjunctival fornix packing
      to conventional instillation of eyedrops containing 2.5% phenylephrine and 1%
      tropicamide in premature infants undergoing examination for retinopathy of
      prematurity. METHODS: The patients were randomized to receive either conventional
      instillation of mydriatic drops or lower conjunctival fornix packing in one eye
      and the alternate method in the fellow eye. For the eyes receiving lower
      conjunctival fornix packing (study group), one small piece of the cotton wool
      soaked with one drop of 2.5% phenylephrine and one drop of 1% tropicamide was
      packed in the lower conjunctival fornix for 15 minutes. For the eyes receiving
      the conventional instillation (control group), 2.5% phenylephrine and 1%
      tropicamide were alternately instilled every 5 minutes for two doses each.
      Horizontal pupil diameter was measured with a ruler in millimeters 40 minutes
      later. RESULTS: The mean dilated pupil diameter in study group and control group
      were 5.76 +/- 1.01 mm and 4.50 +/- 1.08 mm, respectively. This difference was
      statistically significant (P < 0.05). CONCLUSION: The dilated pupil diameter
      after receiving the lower conjunctival fornix packing was larger than
      conventional instillation with a statistically significant difference. We
      recommended the packing method to dilate the preterm infant pupil, especially if
      the pupil is difficult to dilate.

PMID- 22368444
TI  - Management challenges arising from a traumatic 360 degree cyclodialysis cleft.
AB  - We describe the case of a 28-year-old naval officer who attended the
      ophthalmology service following blunt ocular trauma to the left eye. Clinical
      examination revealed a shallow anterior chamber, hypotony, and a 360 degrees 
      cyclodialysis cleft. We discuss the management options in this case, with an
      overview of the current literature.

PMID- 22368445
TI  - Case of bilateral complete posterior dislocation of lens caused by elder abuse.
AB  - We report a case of bilateral complete dislocation of lenses into the vitreous
      cavities due to elder abuse in a patient with senile dementia. According to the
      patient's son, bilateral complete lens dislocation occurred after he hit his
      father in the head with socks in order to control his violent behavior. Although
      the patient was taken to our ophthalmological ward for a planned vitrectomy,
      restlessness and inability to remain in his room during the night led to his
      leaving the hospital. The patient has not returned but did receive a vitrectomy
      at another clinic. While the number of patients with senile dementia has
      dramatically increased, no specific remedy is currently available. When treating
      medical concerns of seniors with unknown backgrounds, elder abuse needs to be
      considered as a potential cause of such injuries.

PMID- 22368446
TI  - Retinopathy and risk factors in diabetic patients from Al-Madinah Al-Munawarah in
      the Kingdom of Saudi Arabia.
AB  - BACKGROUND: Diabetes mellitus is accompanied by chronic and dangerous
      microvascular changes affecting most body systems, especially the eye, leading to
      diabetic retinopathy. Diabetic retinopathy without appropriate management is
      emerging as one of the leading causes of blindness. Therefore, it is necessary to
      improve the early diagnosis of diabetic retinopathy, reduce the risk of
      blindness, and identify relevant risk factors. METHODS: This descriptive study
      was designed to estimate the prevalence of retinopathy and its staging in
      diabetic patients attending the diabetes clinic at King Fahd Hospital in Al
      Madinah Al-Munawarah, Kingdom of Saudi Arabia, from 2008 to 2010. Patients
      completed a questionnaire, underwent a full medical assessment carried out by the
      treating clinicians, and were examined for evidence of diabetic retinopathy using
      standard ophthalmic outpatient instruments. RESULTS: In total, 690 randomly
      selected diabetic patients of mean age 46.10 +/- 11.85 (range 16-88) years were
      included, comprising 395 men (57.2%) of mean age 46.50 +/- 11.31 years and 295
      women (42.8%) of mean age 45.55 +/- 12.53 years. The mean duration of diabetes
      mellitus was 11.91 +/- 7.92 years in the women and 14.42 +/- 8.20 years in the
      men, and the mean total duration of known diabetes mellitus was 13.35 +/- 8.17
      years. Glycated hemoglobin was higher in men (8.53% +/- 1.81%) than in women
      (7.73% +/- 1.84%), and this difference was statistically significant (P <=
      0.0001). Of the 690 diabetic patients, 249 (36.1%) had retinopathy. Mild
      nonproliferative diabetic retinopathy was present in 13.6% of patients, being of
      moderate grade in 8% and of severe grade in 8.1%. A further 6.4% had
      proliferative diabetic retinopathy. CONCLUSION: Regular screening to detect
      diabetic retinopathy is strongly recommended because early detection has the best
      chance of preventing retinal complications.

PMID- 22368447
TI  - Coronary artery disease in Africa and the Middle East.
AB  - Countries in Africa and the Middle East bear a heavy burden from cardiovascular
      disease. The prevalence of coronary heart disease is promoted in turn by a high
      prevalence of cardiovascular risk factors, particularly smoking, hypertension,
      dyslipidemia, diabetes, and sedentary lifestyles. Patients in Africa and the
      Middle East present with myocardial infarction at a younger age, on average,
      compared with patients elsewhere. The projected future burden of mortality from
      coronary heart disease in Africa and the Middle East is set to outstrip that
      observed in other geographical regions. Recent detailed nationally representative
      epidemiological data are lacking for many countries, and high proportions of
      transient expatriate workers in countries such as Saudi Arabia and the United
      Arab Emirates complicate the construction of such datasets. However, the
      development of national registries in some countries is beginning to reveal the
      nature of coronary heart disease. Improving lifestyles (reducing calorie intake
      and increasing physical activity) in patients in the region will be essential,
      although cultural and environmental barriers will render this difficult.
      Appropriate prescribing of pharmacologic treatments is essential in the
      prevention and management of cardiovascular disease. In particular, recent
      controversies relating to the therapeutic profile of beta-blockers may have
      reduced their use. The current evidence base suggests that beta-blockers are as
      effective as other therapies in preventing cardiovascular disease and that
      concerns relating to their use in hypertension and cardiovascular disease have
      been overstated.

PMID- 22368448
TI  - Noninvasive radioelectric asymmetric conveyor brain stimulation treatment
      improves balance in individuals over 65 suffering from neurological diseases:
      pilot study.
AB  - PURPOSE: In the elderly population, problems with walking and balance are very
      common. These problems seriously affect the quality of life of the elderly. When
      gait and balance problems are caused by neurological disease, these problems can
      be more serious and difficult to handle. The aim of this pilot study was to
      verify the effect of a noninvasive radioelectric conveyor asymmetric brain
      stimulation protocol, named neuropostural optimization (NPO), to improve balance
      in neurological elderly. PATIENTS AND METHODS: Twelve patients suffering from
      various neurological diseases participated in this study. They were assessed with
      the Romberg test, which was performed on a computerized stabilometric platform
      before, immediately following, and 72 hours after NPO was used to improve
      balance. RESULTS: The results showed that a stabilization of balance was recorded
      in all subjects a few minutes after administration of NPO. This stabilization
      increased 72 hours after treatment. CONCLUSION: The results show that NPO could
      be a valuable therapeutic approach to improve sensory-motor strategies and
      neurological control of balance in elderly patients suffering from various
      neurological diseases.

PMID- 22368449
TI  - Daptomycin approved in Japan for the treatment of methicillin-resistant
      Staphylococcus aureus.
AB  - Daptomycin is a lipoglycopeptide antibacterial drug that is rapidly bactericidal
      for methicillin-resistant Staphylococcus aureus (MRSA) infection and has
      antibiotic activity against a wide range of Gram-positive organisms. It has been
      approved by the Ministry of Health, Labor and Welfare in Japan for the treatment
      for bacteremia, right-sided endocarditis, and skin and skin-structure infections,
      such as necrotizing fasciitis, due to MRSA on the basis of a Phase III trial
      conducted in Japan since July, 2011. In Japanese Phase I and III trials,
      daptomycin therapy given at 4 mg/kg and 6 mg/kg once per day was well tolerated
      and effective as standard therapy for the treatment of acute bacterial skin and
      skin-structure infections and bacteremia caused by MRSA, but side effects remain
      to be evaluated in large-scale trials.

PMID- 22368450
TI  - Sphincterochilidae from Tunisia, with a note on the subgenus Rima Pallary, 1910
      (Gastropoda, Pulmonata).
AB  - In order to establish an updated checklist of terrestrial gastropod from Tunisia,
      a revision of the species of Sphincterochilidae is presented, using bibliographic
      and museum records and the results of our own field work. As a result, only two
      species, Sphincterochila candidissima and Sphincterochila tunetana, are accepted
      to occur in Tunisia, and their type specimens are illustrated. The study of the
      morphological characters of the genital organs of both species clarified their
      subgeneric affiliation. Comparison of Sphincterochila tunetana with
      Sphincterochila cariosa from Lebanonshowed that the first has to be classified
      within the subgenus Albea, and the latter within Sphincterochila s. str.; the
      subgenus Rima Pallary, 1910 remains in the synonymy of Sphincterochila s. str.
      Bibliographic records of Sphincterochila baetica and Sphincterochila otthiana
      from Tunisia could not be confirmed, the latter probably lives close to the
      border with Algeria.

PMID- 22368451
TI  - Review of the Capitellidae (Annelida, Polychaeta) from the Eastern Tropical
      Pacific region, with notes on selected species.
AB  - The main objective of this work is to contribute to the taxonomic knowledge of
      the species of Capitellidae reported for the Eastern Tropical Pacific. This
      catalogue includes the original name of each species, new names, synonymies, type
      localities, the museum or institution where the type material is deposited,
      revision of the material reported for the region by different authors, new
      examined material, previous reports from other regions of the world, and comments
      on systematics and distributions. The catalogue lists 43 species in 19 genera. Of
      these, 6 species were erroneously recorded for the region (Decamastus gracilis
      Hartman, 1963; Decamastus nudus Thomassin, 1970; Mastobranchus variabilis Edwing,
      1984; Notomastus aberans Day, 1957; Notomastus americanus Day, 1973; Notomastus
      latericeus Sars, 1851) and 5 species are found here to be questionable records
      for the Eastern Tropical Pacific (Capitella capitata (Fabricius, 1780);
      Dasybranchus glabrus Moore, 1909; Decamastus lumbricoides Grube, 1878; Notomastus
      lineatus Claparede, 1870 and Notomastus tenuis Moore, 1909).

PMID- 22368452
TI  - Elmidae (Coleoptera, Byrrhoidea) larvae in the state of Sao Paulo, Brazil:
      Identification key, new records and distribution.
AB  - The family Elmidae Curtis, 1830 has cosmopolitan distribution and most species
      inhabit riffles on streams and rivers, hence the name "riffle beetle". In recent
      years, this family has been featured in papers addressing the assessment and
      environmental monitoring of water quality. In Brazil, studies on the family
      remain scarce and the present investigation is a pioneering study in the state of
      Sao Paulo. This study aims to propose a taxonomic key for the identification of
      larvae of Elmidae genera known to occur in the State, as well as to report new
      records and the distribution of these genera. The material analyzed was collected
      from various locations in each of 15 drainage basins from 2005 to 2010. The
      identification key includes 12 genera (Austrolimnius Carter & Zeck, 1929,
      Heterelmis Sharp, 1882, Hexacylloepus Hinton, 1940, Hexanchorus Sharp, 1882,
      Huleechius Brown, 1981, Macrelmis Motschulsky, 1859, Microcylloepus Hinton, 1935,
      Neoelmis Musgrave, 1935, Phanocerus Sharp, 1882, Potamophilops Grouvelle, 1896,
      Stegoelmis Hinton, 1939 and Xenelmis Hinton, 1936) known in Brazil as well as
      three morphotypes designated herein as Genus A, Genus M and Genus X. The genus
      Hexanchorus is recorded for the first time in the state of Sao Paulo.

PMID- 22368453
TI  - First records of Synoeca septentrionalis Richards, 1978 (Hymenoptera, Vespidae,
      Epiponini) in the Brazilian Atlantic Rain Forest.
AB  - Nests of Synoeca septentrionalis were collected in two Brazilian Atlantic Rain
      Forest localities (Itabuna and Santa Terezinha, in the state of Bahia and Alfredo
      Chaves in the state of Espirito Santo). Synoeca septentrionalis was previously
      recorded only from Central America and northwestern South America. This
      findingextends its geographical distribution to Northeast and Southeast regions
      of Brazil, and represents the first record for Synoeca septentrionalis in the
      Brazilian Atlantic Rain forest, raising to three the number of Synoeca species
      known from Bahia State.

PMID- 22368454
TI  - ?
AB  - Fully dense bulk nanocomposites have been obtained by a novel two-step severe
      plastic deformation process in the immiscible Fe-Cu system. Elemental micrometer
      sized Cu and Fe powders were first mixed in different compositions and
      subsequently high-pressure-torsion-consolidated and deformed in a two-step
      deformation process. Scanning electron microscopy, X-ray diffraction and atom
      probe investigations were performed to study the evolving far-from-equilibrium
      nanostructures which were observed at all compositions. For lower and higher Cu
      contents complete solid solutions of Cu in Fe and Fe in Cu, respectively, are
      obtained. In the near 50% regime a solid solution face-centred cubic and solid
      solution body-centred cubic nanograined composite has been formed. After an
      annealing treatment, these solid solutions decompose and form two-phase
      nanostructured Fe-Cu composites with a high hardness and an enhanced thermal
      stability. The grain size of the composites retained nanocrystalline up to high
      annealing temperatures.

PMID- 22368455
TI  - Attitude determination using a MEMS-based flight information measurement unit.
AB  - Obtaining precise attitude information is essential for aircraft navigation and
      control. This paper presents the results of the attitude determination using an
      in-house designed low-cost MEMS-based flight information measurement unit. This
      study proposes a quaternion-based extended Kalman filter to integrate the
      traditional quaternion and gravitational force decomposition methods for attitude
      determination algorithm. The proposed extended Kalman filter utilizes the
      evolution of the four elements in the quaternion method for attitude
      determination as the dynamic model, with the four elements as the states of the
      filter. The attitude angles obtained from the gravity computations and from the
      electronic magnetic sensors are regarded as the measurement of the filter. The
      immeasurable gravity accelerations are deduced from the outputs of the three axes
      accelerometers, the relative accelerations, and the accelerations due to body
      rotation. The constraint of the four elements of the quaternion method is treated
      as a perfect measurement and is integrated into the filter computation.
      Approximations of the time-varying noise variances of the measured signals are
      discussed and presented with details through Taylor series expansions. The
      algorithm is intuitive, easy to implement, and reliable for long-term high
      dynamic maneuvers. Moreover, a set of flight test data is utilized to demonstrate
      the success and practicality of the proposed algorithm and the filter design.

PMID- 22368456
TI  - The development of a monitoring system using a Wireless and Powerless Sensing
      Node deployed inside a spindle.
AB  - Installation of a Wireless and Powerless Sensing Node (WPSN) inside a spindle
      enables the direct transmission of monitoring signals through a metal case of a
      certain thickness instead of the traditional method of using connecting cables.
      Thus, the node can be conveniently installed inside motors to measure various
      operational parameters. This study extends this earlier finding by applying this
      advantage to the monitoring of spindle systems. After over 2 years of system
      observation and optimization, the system has been verified to be superior to
      traditional methods. The innovation of fault diagnosis in this study includes the
      unmatched assembly dimensions of the spindle system, the unbalanced system, and
      bearing damage. The results of the experiment demonstrate that the WPSN provides
      a desirable signal-to-noise ratio (SNR) in all three of the simulated faults,
      with the difference of SNR reaching a maximum of 8.6 dB. Following multiple
      repetitions of the three experiment types, 80% of the faults were diagnosed when
      the spindle revolved at 4,000 rpm, significantly higher than the 30% fault
      recognition rate of traditional methods. The experimental results of monitoring
      of the spindle production line indicated that monitoring using the WPSN
      encounters less interference from noise compared to that of traditional methods.
      Therefore, this study has successfully developed a prototype concept into a well
      developed monitoring system, and the monitoring can be implemented in a spindle
      production line or real-time monitoring of machine tools.

PMID- 22368457
TI  - Ultrasound nondestructive evaluation (NDE) imaging with transducer arrays and
      adaptive processing.
AB  - This paper addresses the challenging problem of ultrasonic non-destructive
      evaluation (NDE) imaging with adaptive transducer arrays. In NDE applications,
      most materials like concrete, stainless steel and carbon-reinforced composites
      used extensively in industries and civil engineering exhibit heterogeneous
      internal structure. When inspected using ultrasound, the signals from defects are
      significantly corrupted by the echoes form randomly distributed scatterers, even
      defects that are much larger than these random reflectors are difficult to detect
      with the conventional delay-and-sum operation. We propose to apply adaptive
      beamforming to the received data samples to reduce the interference and clutter
      noise. Beamforming is to manipulate the array beam pattern by appropriately
      weighting the per-element delayed data samples prior to summing them. The
      adaptive weights are computed from the statistical analysis of the data samples.
      This delay-weight-and-sum process can be explained as applying a lateral spatial
      filter to the signals across the probe aperture. Simulations show that the
      clutter noise is reduced by more than 30 dB and the lateral resolution is
      enhanced simultaneously when adaptive beamforming is applied. In experiments
      inspecting a steel block with side-drilled holes, good quantitative agreement
      with simulation results is demonstrated.

PMID- 22368458
TI  - Security issues in healthcare applications using wireless medical sensor
      networks: a survey.
AB  - Healthcare applications are considered as promising fields for wireless sensor
      networks, where patients can be monitored using wireless medical sensor networks
      (WMSNs). Current WMSN healthcare research trends focus on patient reliable
      communication, patient mobility, and energy-efficient routing, as a few examples.
      However, deploying new technologies in healthcare applications without
      considering security makes patient privacy vulnerable. Moreover, the
      physiological data of an individual are highly sensitive. Therefore, security is
      a paramount requirement of healthcare applications, especially in the case of
      patient privacy, if the patient has an embarrassing disease. This paper discusses
      the security and privacy issues in healthcare application using WMSNs. We
      highlight some popular healthcare projects using wireless medical sensor
      networks, and discuss their security. Our aim is to instigate discussion on these
      critical issues since the success of healthcare application depends directly on
      patient security and privacy, for ethic as well as legal reasons. In addition, we
      discuss the issues with existing security mechanisms, and sketch out the
      important security requirements for such applications. In addition, the paper
      reviews existing schemes that have been recently proposed to provide security
      solutions in wireless healthcare scenarios. Finally, the paper ends up with a
      summary of open security research issues that need to be explored for future
      healthcare applications using WMSNs.

PMID- 22368459
TI  - An energy efficient cooperative hierarchical MIMO clustering scheme for wireless
      sensor networks.
AB  - In this work, we present an energy efficient hierarchical cooperative clustering
      scheme for wireless sensor networks. Communication cost is a crucial factor in
      depleting the energy of sensor nodes. In the proposed scheme, nodes cooperate to
      form clusters at each level of network hierarchy ensuring maximal coverage and
      minimal energy expenditure with relatively uniform distribution of load within
      the network. Performance is enhanced by cooperative multiple-input multiple
      output (MIMO) communication ensuring energy efficiency for WSN deployments over
      large geographical areas. We test our scheme using TOSSIM and compare the
      proposed scheme with cooperative multiple-input multiple-output (CMIMO)
      clustering scheme and traditional multihop Single-Input-Single-Output (SISO)
      routing approach. Performance is evaluated on the basis of number of clusters,
      number of hops, energy consumption and network lifetime. Experimental results
      show significant energy conservation and increase in network lifetime as compared
      to existing schemes.

PMID- 22368460
TI  - FPGA-based real-time embedded system for RISS/GPS integrated navigation.
AB  - Navigation algorithms integrating measurements from multi-sensor systems overcome
      the problems that arise from using GPS navigation systems in standalone mode.
      Algorithms which integrate the data from 2D low-cost reduced inertial sensor
      system (RISS), consisting of a gyroscope and an odometer or wheel encoders, along
      with a GPS receiver via a Kalman filter has proved to be worthy in providing a
      consistent and more reliable navigation solution compared to standalone GPS
      receivers. It has been also shown to be beneficial, especially in GPS-denied
      environments such as urban canyons and tunnels. The main objective of this paper
      is to narrow the idea-to-implementation gap that follows the algorithm
      development by realizing a low-cost real-time embedded navigation system capable
      of computing the data-fused positioning solution. The role of the developed
      system is to synchronize the measurements from the three sensors, relative to the
      pulse per second signal generated from the GPS, after which the navigation
      algorithm is applied to the synchronized measurements to compute the navigation
      solution in real-time. Employing a customizable soft-core processor on an FPGA in
      the kernel of the navigation system, provided the flexibility for communicating
      with the various sensors and the computation capability required by the Kalman
      filter integration algorithm.

PMID- 22368461
TI  - Voltammetric determination of the herbicide Linuron using a tricresyl phosphate
      based carbon paste electrode.
AB  - This paper summarises the results of voltammetric studies on the herbicide 3-(3,4
      dichlorophenyl)-1-methoxy-1-methylurea (Linuron), using a carbon paste electrode
      containing tricresyl phosphate (TCP-CPE) as liquid binder. The principal
      experimental conditions, such as the pH effect, investigated in Britton-Robinson
      buffer solutions (pH 2.0-7.0), the peak characteristics for the analyte of
      interest, or instrumental parameters for the differential pulse voltammetric mode
      were optimized for the method. As found out, the best electroanalytical
      performance of the TCP-CPE was achieved at pH 2.0, whereby the oxidation peak of
      Linuron appeared at ca. +1.3 V vs. SCE. The analytical procedure developed offers
      good linearity in the concentration range of 1.25-44.20 MUg mL(-1) (1.77 * 10(-4)
      5.05 * 10(-6) mol L(-1)), showing-for the first time-the applicability of the TCP
      CPE for anodic oxidations in direct voltammetry (without accumulation). The
      method was then verified by determining Linuron in a spiked river water sample
      and a commercial formulation and the results obtained agreed well with those
      obtained by the reference HPLC/UV determination.

PMID- 22368462
TI  - Tongue tumor detection in medical hyperspectral images.
AB  - A hyperspectral imaging system to measure and analyze the reflectance spectra of
      the human tongue with high spatial resolution is proposed for tongue tumor
      detection. To achieve fast and accurate performance for detecting tongue tumors,
      reflectance data were collected using spectral acousto-optic tunable filters and
      a spectral adapter, and sparse representation was used for the data analysis
      algorithm. Based on the tumor image database, a recognition rate of 96.5% was
      achieved. The experimental results show that hyperspectral imaging for tongue
      tumor diagnosis, together with the spectroscopic classification method provide a
      new approach for the noninvasive computer-aided diagnosis of tongue tumors.

PMID- 22368463
TI  - Development of a hybrid atomic force microscopic measurement system combined with
      white light scanning interferometry.
AB  - A hybrid atomic force microscopic (AFM) measurement system combined with white
      light scanning interferometry for micro/nanometer dimensional measurement is
      developed. The system is based on a high precision large-range positioning
      platform with nanometer accuracy on which a white light scanning interferometric
      module and an AFM head are built. A compact AFM head is developed using a self
      sensing tuning fork probe. The head need no external optical sensors to detect
      the deflection of the cantilever, which saves room on the head, and it can be
      directly fixed under an optical microscopic interferometric system. To enhance
      the system's dynamic response, the frequency modulation (FM) mode is adopted for
      the AFM head. The measuring data can be traceable through three laser
      interferometers in the system. The lateral scanning range can reach 25 mm * 25 mm
      by using a large-range positioning platform. A hybrid method combining AFM and
      white light scanning interferometry is proposed to improve the AFM measurement
      efficiency. In this method, the sample is measured firstly by white light
      scanning interferometry to get an overall coarse morphology, and then, further
      measured with higher resolution by AFM. Several measuring experiments on standard
      samples demonstrate the system's good measurement performance and feasibility of
      the hybrid measurement method.

PMID- 22368464
TI  - Hierarchical leak detection and localization method in natural gas pipeline
      monitoring sensor networks.
AB  - In light of the problems of low recognition efficiency, high false rates and poor
      localization accuracy in traditional pipeline security detection technology, this
      paper proposes a type of hierarchical leak detection and localization method for
      use in natural gas pipeline monitoring sensor networks. In the signal
      preprocessing phase, original monitoring signals are dealt with by wavelet
      transform technology to extract the single mode signals as well as characteristic
      parameters. In the initial recognition phase, a multi-classifier model based on
      SVM is constructed and characteristic parameters are sent as input vectors to the
      multi-classifier for initial recognition. In the final decision phase, an
      improved evidence combination rule is designed to integrate initial recognition
      results for final decisions. Furthermore, a weighted average localization
      algorithm based on time difference of arrival is introduced for determining the
      leak point's position. Experimental results illustrate that this hierarchical
      pipeline leak detection and localization method could effectively improve the
      accuracy of the leak point localization and reduce the undetected rate as well as
      false alarm rate.

PMID- 22368465
TI  - Online assessment of human-robot interaction for hybrid control of walking.
AB  - Restoration of walking ability of Spinal Cord Injury subjects can be achieved by
      different approaches, as the use of robotic exoskeletons or electrical
      stimulation of the user's muscles. The combined (hybrid) approach has the
      potential to provide a solution to the drawback of each approach. Specific
      challenges must be addressed with specific sensory systems and control
      strategies. In this paper we present a system and a procedure to estimate muscle
      fatigue from online physical interaction assessment to provide hybrid control of
      walking, regarding the performances of the muscles under stimulation.

PMID- 22368466
TI  - Self-calibrated humidity sensor in CMOS without post-processing.
AB  - A 1.1 MUW power dissipation, voltage-output humidity sensor with 10% relative
      humidity accuracy was developed in the LFoundry 0.15 MUm CMOS technology without
      post-processing. The sensor consists of a woven lateral array of electrodes
      implemented in CMOS top metal, a humidity-sensitive layer of Intervia
      Photodielectric 8023D-10, a CMOS capacitance to voltage converter, and the self
      calibration circuitry.

PMID- 22368467
TI  - A theoretical model to predict both horizontal displacement and vertical
      displacement for electromagnetic induction-based deep displacement sensors.
AB  - Deep displacement observation is one basic means of landslide dynamic study and
      early warning monitoring and a key part of engineering geological investigation.
      In our previous work, we proposed a novel electromagnetic induction-based deep
      displacement sensor (I-type) to predict deep horizontal displacement and a
      theoretical model called equation-based equivalent loop approach (EELA) to
      describe its sensing characters. However in many landslide and related geological
      engineering cases, both horizontal displacement and vertical displacement vary
      apparently and dynamically so both may require monitoring. In this study, a II
      type deep displacement sensor is designed by revising our I-type sensor to
      simultaneously monitor the deep horizontal displacement and vertical displacement
      variations at different depths within a sliding mass. Meanwhile, a new
      theoretical modeling called the numerical integration-based equivalent loop
      approach (NIELA) has been proposed to quantitatively depict II-type sensors'
      mutual inductance properties with respect to predicted horizontal displacements
      and vertical displacements. After detailed examinations and comparative studies
      between measured mutual inductance voltage, NIELA-based mutual inductance and
      EELA-based mutual inductance, NIELA has verified to be an effective and quite
      accurate analytic model for characterization of II-type sensors. The NIELA model
      is widely applicable for II-type sensors' monitoring on all kinds of landslides
      and other related geohazards with satisfactory estimation accuracy and
      calculation efficiency.

PMID- 22368468
TI  - Rapid classification of hairtail fish and pork freshness using an electronic nose
      based on the PCA method.
AB  - We report a method for building a simple and reproducible electronic nose based
      on commercially available metal oxide sensors (MOS) to monitor the freshness of
      hairtail fish and pork stored at 15, 10, and 5  degrees C. After assembly in the
      laboratory, the proposed product was tested by a manufacturer. Sample delivery
      was based on the dynamic headspace method, and two features were extracted from
      the transient response of each sensor using an unsupervised principal component
      analysis (PCA) method. The compensation method and pattern recognition based on
      PCA are discussed in the current paper. PCA compensation can be used for all
      storage temperatures, however, pattern recognition differs according to storage
      conditions. Total volatile basic nitrogen (TVBN) and aerobic bacterial counts of
      the samples were measured simultaneously with the standard indicators of hairtail
      fish and pork freshness. The PCA models based on TVBN and aerobic bacterial
      counts were used to classify hairtail fish samples as "fresh" (TVBN <= 25 g and
      microbial counts <= 10(6) cfu/g) or "spoiled" (TVBN >= 25 g and microbial counts
      >= 10(6) cfu/g) and pork samples also as "fresh" (TVBN <= 15 g and microbial
      counts <= 10(6) cfu/g) or "spoiled" (TVBN >= 15 g and microbial counts >= 10(6)
      cfu/g). Good correlation coefficients between the responses of the electronic
      nose and the TVBN and aerobic bacterial counts of the samples were obtained. For
      hairtail fish, correlation coefficients were 0.97 and 0.91, and for pork,
      correlation coefficients were 0.81 and 0.88, respectively. Through laboratory
      simulation and field application, we were able to determine that the electronic
      nose could help ensure the shelf life of hairtail fish and pork, especially when
      an instrument is needed to take measurements rapidly. The results also showed
      that the electronic nose could analyze the process and level of spoilage for
      hairtail fish and pork.

PMID- 22368469
TI  - Fusion of a variable baseline system and a range finder.
AB  - One of the greatest difficulties in stereo vision is the appearance of
      ambiguities when matching similar points from different images. In this article
      we analyze the effectiveness of using a fusion of multiple baselines and a range
      finder from a theoretical point of view, focusing on the results of using both
      prismatic and rotational articulations for baseline generation, and offer a
      practical case to prove its efficiency on an autonomous vehicle.

PMID- 22368470
TI  - Modulation techniques for biomedical implanted devices and their challenges.
AB  - Implanted medical devices are very important electronic devices because of their
      usefulness in monitoring and diagnosis, safety and comfort for patients. Since
      1950s, remarkable efforts have been undertaken for the development of bio-medical
      implanted and wireless telemetry bio-devices. Issues such as design of suitable
      modulation methods, use of power and monitoring devices, transfer energy from
      external to internal parts with high efficiency and high data rates and low power
      consumption all play an important role in the development of implantable devices.
      This paper provides a comprehensive survey on various modulation and demodulation
      techniques such as amplitude shift keying (ASK), frequency shift keying (FSK) and
      phase shift keying (PSK) of the existing wireless implanted devices. The details
      of specifications, including carrier frequency, CMOS size, data rate, power
      consumption and supply, chip area and application of the various modulation
      schemes of the implanted devices are investigated and summarized in the tables
      along with the corresponding key references. Current challenges and problems of
      the typical modulation applications of these technologies are illustrated with a
      brief suggestions and discussion for the progress of implanted device research in
      the future. It is observed that the prime requisites for the good quality of the
      implanted devices and their reliability are the energy transformation, data rate,
      CMOS size, power consumption and operation frequency. This review will hopefully
      lead to increasing efforts towards the development of low powered, high
      efficient, high data rate and reliable implanted devices.

PMID- 22368471
TI  - Ceramic MEMS designed for wireless pressure monitoring in the industrial
      environment.
AB  - This paper presents the design of a wireless pressure-monitoring system for harsh
      environment applications. Two types of ceramic pressure sensors made with a low
      temperature cofired ceramic (LTCC) were considered. The first type is a
      piezoresistive strain gauge pressure sensor. The second type is a capacitive
      pressure sensor, which is based on changes of the capacitance values between two
      electrodes: one electrode is fixed and the other is movable under an applied
      pressure. The design was primarily focused on low power consumption. Reliable
      operation in the presence of disturbances, like electromagnetic interference,
      parasitic capacitances, etc., proved to be contradictory constraints. A
      piezoresistive ceramic pressure sensor with a high bridge impedance was chosen
      for use in a wireless pressure-monitoring system and an acceptable solution using
      energy-harvesting techniques has been achieved. The described solution allows for
      the integration of a sensor element with an energy harvester that has a printed
      thick-film battery and complete electronics in a single substrate packaged inside
      a compact housing.

PMID- 22368472
TI  - Computer vision based method and system for online measurement of geometric
      parameters of train wheel sets.
AB  - Train wheel sets must be periodically inspected for possible or actual premature
      failures and it is very significant to record the wear history for the full life
      of utilization of wheel sets. This means that an online measuring system could be
      of great benefit to overall process control. An online non-contact method for
      measuring a wheel set's geometric parameters based on the opto-electronic
      measuring technique is presented in this paper. A charge coupled device (CCD)
      camera with a selected optical lens and a frame grabber was used to capture the
      image of the light profile of the wheel set illuminated by a linear laser. The
      analogue signals of the image were transformed into corresponding digital grey
      level values. The 'mapping function method' is used to transform an image pixel
      coordinate to a space coordinate. The images of wheel sets were captured when the
      train passed through the measuring system. The rim inside thickness and flange
      thickness were measured and analyzed. The spatial resolution of the whole image
      capturing system is about 0.33 mm. Theoretic and experimental results show that
      the online measurement system based on computer vision can meet wheel set
      measurement requirements.

PMID- 22368473
TI  - Single-cell chemical lysis on microfluidic chips with arrays of microwells.
AB  - Many conventional biochemical assays are performed using populations of cells to
      determine their quantitative biomolecular profiles. However, population averages
      do not reflect actual physiological processes in individual cells, which occur
      either on short time scales or nonsynchronously. Therefore, accurate analysis at
      the single-cell level has become a highly attractive tool for investigating
      cellular content. Microfluidic chips with arrays of microwells were developed for
      single-cell chemical lysis in the present study. The cellular occupancy in 30-MUm
      diameter microwells (91.45%) was higher than that in 20-MUm-diameter microwells
      (83.19%) at an injection flow rate of 2.8 MUL/min. However, most of the occupied
      20-MUm-diameter microwells contained individual cells. The results of chemical
      lysis experiments at the single-cell level indicate that cell membranes were
      gradually lysed as the lysis buffer was injected; they were fully lysed after 12
      s. Single-cell chemical lysis was demonstrated in the proposed microfluidic chip,
      which is suitable for high-throughput cell lysis.

PMID- 22368474
TI  - BIPV-powered smart windows utilizing photovoltaic and electrochromic devices.
AB  - A BIPV-powered smart window comprising a building-integrated photovoltaic (BIPV)
      panel and an all-solid-state electrochromic (EC) stack is proposed. In the
      proposed device, the output voltage of the BIPV panel varies in accordance with
      the intensity of the incident light and is modulated in such a way as to generate
      the EC stack voltage required to maintain the indoor illuminance within a
      specified range. Two different EC stacks are fabricated and characterized, namely
      one stack comprising ITO/WO(3)/Ta(2)O(5)/ITO and one stack comprising
      ITO/WO(3)/lithium-polymer electrolyte/ITO. It is shown that of the two stacks,
      the ITO/WO(3)/lithium-polymer electrolyte/ITO stack has a larger absorptance
      (i.e., approximately 99% at a driving voltage of 3.5 V). The experimental results
      show that the smart window incorporating an ITO/WO(3)/lithium-polymer
      electrolyte/ITO stack with an electrolyte thickness of 1.0 MUm provides an indoor
      illuminance range of 750-1,500 Lux under typical summertime conditions in Taiwan.

PMID- 22368475
TI  - Marine vehicle sensor network architecture and protocol designs for ocean
      observation.
AB  - The micro-scale and meso-scale ocean dynamic processes which are nonlinear and
      have large variability, have a significant impact on the fisheries, natural
      resources, and marine climatology. A rapid, refined and sophisticated observation
      system is therefore needed in marine scientific research. The maneuverability and
      controllability of mobile sensor platforms make them a preferred choice to
      establish ocean observing networks, compared to the static sensor observing
      platform. In this study, marine vehicles are utilized as the nodes of mobile
      sensor networks for coverage sampling of a regional ocean area and ocean feature
      tracking. A synoptic analysis about marine vehicle dynamic control, multi
      vehicles mission assignment and path planning methods, and ocean feature tracking
      and observing techniques is given. Combined with the observation plan in the
      South China Sea, we provide an overview of the mobile sensor networks established
      with marine vehicles, and the corresponding simulation results.

PMID- 22368476
TI  - Ubiquitous Sensor Networking for Development (USN4D): an application to pollution
      monitoring.
AB  - This paper presents a new Ubiquitous Sensor Network (USN) Architecture to be used
      in developing countries and reveals its usefulness by highlighting some of its
      key features. In complement to a previous ITU proposal, our architecture referred
      to as "Ubiquitous Sensor Network for Development (USN4D)" integrates in its
      layers features such as opportunistic data dissemination, long distance
      deployment and localisation of information to meet the requirements of the
      developing world. Besides describing some of the most important requirements for
      the sensor equipment to be used in a USN4D setting, we present the main features
      and experiments conducted using the "WaspNet" as one of the wireless sensor
      deployment platforms that meets these requirements. Furthermore, building upon
      "WaspNet" platform, we present an application to Air pollution Monitoring in the
      city of Cape Town, in South Africa as one of the first steps towards building
      community wireless sensor networks (CSN) in the developing world using off-the
      shelf sensor equipment.

PMID- 22368477
TI  - An intrinsic fiber-optic single loop micro-displacement sensor.
AB  - A micro-displacement sensor consisting of a fiber-loop made with a tapered fiber
      is reported. The sensor operation is based on the interaction between the
      fundamental cladding mode propagating through the taper waist and higher order
      cladding modes excited when the taper is deformed to form a loop. As a result, a
      transmission spectrum with several notches is observed, where the notch
      wavelength resonances shift as a function of the loop diameter. The loop diameter
      is varied by the spatial displacement of one end of the fiber-loop attached to a
      linear translation stage. In a displacement range of 3.125 mm the maximum
      wavelength shift is 360.93 nm, with 0.116 nm/MUm sensitivity. By using a 1,280 nm
      broadband low-power LED source and a single Ge-photodetector in a power
      transmission sensor setup, a sensitivity in the order of 2.7 nW/MUm is obtained
      in ~ 1 mm range. The proposed sensor is easy to implement and has a plenty of
      room to improve its performance.

PMID- 22368478
TI  - Sensor fusion of monocular cameras and laser rangefinders for line-based
      Simultaneous Localization and Mapping (SLAM) tasks in autonomous mobile robots.
AB  - This paper presents a sensor fusion strategy applied for Simultaneous
      Localization and Mapping (SLAM) in dynamic environments. The designed approach
      consists of two features: (i) the first one is a fusion module which synthesizes
      line segments obtained from laser rangefinder and line features extracted from
      monocular camera. This policy eliminates any pseudo segments that appear from any
      momentary pause of dynamic objects in laser data. (ii) The second characteristic
      is a modified multi-sensor point estimation fusion SLAM (MPEF-SLAM) that
      incorporates two individual Extended Kalman Filter (EKF) based SLAM algorithms:
      monocular and laser SLAM. The error of the localization in fused SLAM is reduced
      compared with those of individual SLAM. Additionally, a new data association
      technique based on the homography transformation matrix is developed for
      monocular SLAM. This data association method relaxes the pleonastic computation.
      The experimental results validate the performance of the proposed sensor fusion
      and data association method.

PMID- 22368479
TI  - Point cloud generation from aerial image data acquired by a quadrocopter type
      micro unmanned aerial vehicle and a digital still camera.
AB  - The objective of this investigation was to develop and investigate methods for
      point cloud generation by image matching using aerial image data collected by
      quadrocopter type micro unmanned aerial vehicle (UAV) imaging systems. Automatic
      generation of high-quality, dense point clouds from digital images by image
      matching is a recent, cutting-edge step forward in digital photogrammetric
      technology. The major components of the system for point cloud generation are a
      UAV imaging system, an image data collection process using high image overlaps,
      and post-processing with image orientation and point cloud generation. Two post
      processing approaches were developed: one of the methods is based on Bae Systems'
      SOCET SET classical commercial photogrammetric software and another is built
      using Microsoft((r))'s PhotosynthTM service available in the Internet. Empirical
      testing was carried out in two test areas. Photosynth processing showed that it
      is possible to orient the images and generate point clouds fully automatically
      without any a priori orientation information or interactive work. The
      photogrammetric processing line provided dense and accurate point clouds that
      followed the theoretical principles of photogrammetry, but also some artifacts
      were detected. The point clouds from the Photosynth processing were sparser and
      noisier, which is to a large extent due to the fact that the method is not
      optimized for dense point cloud generation. Careful photogrammetric processing
      with self-calibration is required to achieve the highest accuracy. Our results
      demonstrate the high performance potential of the approach and that with rigorous
      processing it is possible to reach results that are consistent with theory. We
      also point out several further research topics. Based on theoretical and
      empirical results, we give recommendations for properties of imaging sensor, data
      collection and processing of UAV image data to ensure accurate point cloud
      generation.

PMID- 22368480
TI  - Measurement of organic chemical refractive indexes using an optical time-domain
      reflectometer.
AB  - In this investigation, we propose and experimentally demonstrate a method for
      measuring the refractive index (RI) of liquid organic chemicals. The scheme is
      based on a single-mode fiber (SMF) sensor and an optical time-domain
      reflectometer (OTDR). Here, due to the different reflectance (R) between the SMF
      and organic liquid chemicals, the reflected power level of the backscattering
      light (BSL) measured by the OTDR would be different. Therefore, we can measure
      the RI of chemical under test via the measured BSL level. The proposed RI sensor
      is simple and easy to manipulate, with stable detected signals, and has the
      potential to be a valuable tool for use in biological and chemical applications.

PMID- 22368481
TI  - A wireless sEMG recording system and its application to muscle fatigue detection.
AB  - Surface electromyography (sEMG) is an important measurement for monitoring
      exercise and fitness. Because if its high sampling frequency requirement,
      wireless transmission of sEMG data is a challenge. In this article a wireless
      sEMG measurement system with a sampling frequency of 2 KHz is developed based
      upon a MSP 430 microcontroller and Bluetooth transmission. Standard isotonic and
      isometric muscle contraction are clearly represented in the receiving user
      interface. Muscle fatigue detection is an important application of sEMG.
      Traditional muscle fatigue is detected from the median frequency of the sEMG
      power spectrum. The regression slope of the linear regression of median frequency
      is an important muscle fatigue index. A more negative slope value represents a
      higher muscle fatigue condition. To test the system performance, muscle fatigue
      detection was examined by having subjects run on a pedaled-multifunctional
      elliptical trainer for approximately 30 minutes at three loading levels. Ten
      subjects underwent a total of 60 exercise sessions to provide the experimental
      data. Results showed that the regression slope gradually decreases as expected,
      and there is a significant gender difference.

PMID- 22368482
TI  - Performance evaluation of multi-channel wireless mesh networks with embedded
      systems.
AB  - Many commercial wireless mesh network (WMN) products are available in the
      marketplace with their own proprietary standards, but interoperability among the
      different vendors is not possible. Open source communities have their own WMN
      implementation in accordance with the IEEE 802.11s draft standard, Linux
      open80211s project and FreeBSD WMN implementation. While some studies have
      focused on the test bed of WMNs based on the open80211s project, none are based
      on the FreeBSD. In this paper, we built an embedded system using the FreeBSD WMN
      implementation that utilizes two channels and evaluated its performance. This
      implementation allows the legacy system to connect to the WMN independent of the
      type of platform and distributes the load between the two non-overlapping
      channels. One channel is used for the backhaul connection and the other one is
      used to connect to the stations to wireless mesh network. By using the power
      efficient 802.11 technology, this device can also be used as a gateway for the
      wireless sensor network (WSN).

PMID- 22368483
TI  - A magnetic flux leakage and magnetostrictive guided wave hybrid transducer for
      detecting bridge cables.
AB  - Condition assessment of cables has gained considerable attention for the bridge
      safety. A magnetic flux leakage and magnetostrictive guided wave hybrid
      transducer is provided to inspect bridge cables. The similarities and differences
      between the two methods are investigated. The hybrid transducer for bridge cables
      consists of an aluminum framework, climbing modules, embedded magnetizers and a
      ribbon coil. The static axial magnetic field provided by the magnetizers meets
      the needs of the magnetic flux leakage testing and the magnetostrictive guided
      wave testing. The magnetizers also provide the attraction for the climbing
      modules. In the magnetic flux leakage testing for the free length of cable, the
      coil induces the axial leakage magnetic field. In the magnetostrictive guided
      wave testing for the anchorage zone, the coil provides a pulse high power
      variational magnetic field for generating guided waves; the coil induces the
      magnetic field variation for receiving guided waves. The experimental results
      show that the transducer with the corresponding inspection system could be
      applied to detect the broken wires in the free length and in the anchorage zone
      of bridge cables.

PMID- 22368484
TI  - Improvement of pyroelectric cells for thermal energy harvesting.
AB  - This study proposes trenching piezoelectric (PZT) material in a thicker PZT
      pyroelectric cell to improve the temperature variation rate to enhance the
      efficiency of thermal energy-harvesting conversion by pyroelectricity. A thicker
      pyroelectric cell is beneficial in generating electricity pyroelectrically, but
      it hinders rapid temperature variations. Therefore, the PZT sheet was fabricated
      to produce deeper trenches to cause lateral temperature gradients induced by the
      trenched electrode, enhancing the temperature variation rate under homogeneous
      heat irradiation. When the trenched electrode type with an electrode width of 200
      MUm and a cutting depth of 150 MUm was used to fabricate a PZT pyroelectric cell
      with a 200 MUm thick PZT sheet, the temperature variation rate was improved by
      about 55%. Therefore, the trenched electrode design did indeed enhance the
      temperature variation rate and the efficiency of pyroelectric energy converters.

PMID- 22368486
TI  - Visual sensor based abnormal event detection with moving shadow removal in home
      healthcare applications.
AB  - Vision-based abnormal event detection for home healthcare systems can be greatly
      improved using visual sensor-based techniques able to detect, track and recognize
      objects in the scene. However, in moving object detection and tracking processes,
      moving cast shadows can be misclassified as part of objects or moving objects.
      Shadow removal is an essential step for developing video surveillance systems.
      The goal of the primary is to design novel computer vision techniques that can
      extract objects more accurately and discriminate between abnormal and normal
      activities. To improve the accuracy of object detection and tracking, our
      proposed shadow removal algorithm is employed. Abnormal event detection based on
      visual sensor by using shape features variation and 3-D trajectory is presented
      to overcome the low fall detection rate. The experimental results showed that the
      success rate of detecting abnormal events was 97% with a false positive rate of
      2%. Our proposed algorithm can allow distinguishing diverse fall activities such
      as forward falls, backward falls, and falling asides from normal activities.

PMID- 22368485
TI  - Exploring transduction mechanisms of protein transduction domains (PTDs) in
      living cells utilizing single-quantum dot tracking (SQT) technology.
AB  - Specific protein domains known as protein transduction domains (PTDs) can
      permeate cell membranes and deliver proteins or bioactive materials into living
      cells. Various approaches have been applied for improving their transduction
      efficacy. It is, therefore, crucial to clarify the entry mechanisms and to
      identify the rate-limiting steps. Because of technical limitations for imaging
      PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the
      cells has been a topic of much debate. Utilizing quantum dots (QDs), we recently
      tracked the behavior of PTD that was derived from HIV-1 Tat (TatP) in living
      cells at the single-molecule level with 7-nm special precision. In this review
      article, we initially summarize the controversy on TatP entry mechanisms;
      thereafter, we will focus on our recent findings on single-TatP-QD tracking
      (SQT), to identify the major sequential steps of intracellular delivery in living
      cells and to discuss how SQT can easily provide direct information on TatP entry
      mechanisms. As a primer for SQT study, we also discuss the latest findings on
      single particle tracking of various molecules on the plasma membrane. Finally, we
      discuss the problems of QDs and the challenges for the future in utilizing
      currently available QD probes for SQT. In conclusion, direct identification of
      the rate-limiting steps of PTD entry with SQT should dramatically improve the
      methods for enhancing transduction efficiency.

PMID- 22368487
TI  - FPGA implementation for real-time background subtraction based on Horprasert
      model.
AB  - Background subtraction is considered the first processing stage in video
      surveillance systems, and consists of determining objects in movement in a scene
      captured by a static camera. It is an intensive task with a high computational
      cost. This work proposes an embedded novel architecture on FPGA which is able to
      extract the background on resource-limited environments and offers low
      degradation (produced because of the hardware-friendly model modification). In
      addition, the original model is extended in order to detect shadows and improve
      the quality of the segmentation of the moving objects. We have analyzed the
      resource consumption and performance in Spartan3 Xilinx FPGAs and compared to
      others works available on the literature, showing that the current architecture
      is a good trade-off in terms of accuracy, performance and resources utilization.
      With less than a 65% of the resources utilization of a XC3SD3400 Spartan-3A low
      cost family FPGA, the system achieves a frequency of 66.5 MHz reaching 32.8 fps
      with resolution 1,024 * 1,024 pixels, and an estimated power consumption of 5.76
      W.

PMID- 22368489
TI  - Toward sensor-based context aware systems.
AB  - This paper proposes a methodology for sensor data interpretation that can combine
      sensor outputs with contexts represented as sets of annotated business rules.
      Sensor readings are interpreted to generate events labeled with the appropriate
      type and level of uncertainty. Then, the appropriate context is selected.
      Reconciliation of different uncertainty types is achieved by a simple technique
      that moves uncertainty from events to business rules by generating combs of
      standard Boolean predicates. Finally, context rules are evaluated together with
      the events to take a decision. The feasibility of our idea is demonstrated via a
      case study where a context-reasoning engine has been connected to simulated
      heartbeat sensors using prerecorded experimental data. We use sensor outputs to
      identify the proper context of operation of a system and trigger decision-making
      based on context information.

PMID- 22368488
TI  - Aptamers and their biological applications.
AB  - Recently, aptamers have attracted the attention of many scientists, because they
      not only have all of the advantages of antibodies, but also have unique merits,
      such as thermal stability, low cost, and unlimited applications. In this review,
      we present the reasons why aptamers are known as alternatives to antibodies.
      Furthermore, several types of in vitro selection processes, including
      nitrocellulose membrane filtration, affinity chromatography, magnetic bead, and
      capillary electrophoresis-based selection methods, are explained in detail. We
      also introduce various applications of aptamers for the diagnosis of diseases and
      detection of small molecules. Numerous analytical techniques, such as
      electrochemical, colorimetric, optical, and mass-sensitive methods, can be
      utilized to detect targets, due to convenient modifications and the stability of
      aptamers. Finally, several medical and analytical applications of aptamers are
      presented. In summary, aptamers are promising materials for diverse areas, not
      just as alternatives to antibodies, but as the core components of medical and
      analytical equipment.

PMID- 22368490
TI  - Multipath routing in wireless sensor networks: survey and research challenges.
AB  - A wireless sensor network is a large collection of sensor nodes with limited
      power supply and constrained computational capability. Due to the restricted
      communication range and high density of sensor nodes, packet forwarding in sensor
      networks is usually performed through multi-hop data transmission. Therefore,
      routing in wireless sensor networks has been considered an important field of
      research over the past decade. Nowadays, multipath routing approach is widely
      used in wireless sensor networks to improve network performance through efficient
      utilization of available network resources. Accordingly, the main aim of this
      survey is to present the concept of the multipath routing approach and its
      fundamental challenges, as well as the basic motivations for utilizing this
      technique in wireless sensor networks. In addition, we present a comprehensive
      taxonomy on the existing multipath routing protocols, which are especially
      designed for wireless sensor networks. We highlight the primary motivation behind
      the development of each protocol category and explain the operation of different
      protocols in detail, with emphasis on their advantages and disadvantages.
      Furthermore, this paper compares and summarizes the state-of-the-art multipath
      routing techniques from the network application point of view. Finally, we
      identify open issues for further research in the development of multipath routing
      protocols for wireless sensor networks.

PMID- 22368491
TI  - A feedfordward adaptive controller to reduce the imaging time of large-sized
      biological samples with a SPM-based multiprobe station.
AB  - The time required to image large samples is an important limiting factor in SPM
      based systems. In multiprobe setups, especially when working with biological
      samples, this drawback can make impossible to conduct certain experiments. In
      this work, we present a feedfordward controller based on bang-bang and adaptive
      controls. The controls are based in the difference between the maximum speeds
      that can be used for imaging depending on the flatness of the sample zone.
      Topographic images of Escherichia coli bacteria samples were acquired using the
      implemented controllers. Results show that to go faster in the flat zones, rather
      than using a constant scanning speed for the whole image, speeds up the imaging
      process of large samples by up to a 4* factor.

PMID- 22368492
TI  - Underwater sensor networks: a new energy efficient and robust architecture.
AB  - The specific characteristics of underwater environments introduce new challenges
      for networking protocols. In this paper, a specialized architecture for
      underwater sensor networks (UWSNs) is proposed and evaluated. Experiments are
      conducted in order to analyze the suitability of this protocol for the subaquatic
      transmission medium. Moreover, different scheduling techniques are applied to the
      architecture in order to study their performance. In addition, given the harsh
      conditions of the underwater medium, different retransmission methods are
      combined with the scheduling techniques. Finally, simulation results illustrate
      the performance achievements of the proposed protocol in end-to-end delay, packet
      delivery ratio and energy consumption, showing that this protocol can be very
      suitable for the underwater medium.

PMID- 22368494
TI  - Soil moisture sensing via swept frequency based microwave sensors.
AB  - There is a need for low-cost, high-accuracy measurement of water content in
      various materials. This study assesses the performance of a new microwave swept
      frequency domain instrument (SFI) that has promise to provide a low-cost, high
      accuracy alternative to the traditional and more expensive time domain
      reflectometry (TDR). The technique obtains permittivity measurements of soils in
      the frequency domain utilizing a through transmission configuration,
      transmissometry, which provides a frequency domain transmissometry measurement
      (FDT). The measurement is comparable to time domain transmissometry (TDT) with
      the added advantage of also being able to separately quantify the real and
      imaginary portions of the complex permittivity so that the measured bulk
      permittivity is more accurate that the measurement TDR provides where the
      apparent permittivity is impacted by the signal loss, which can be significant in
      heavier soils. The experimental SFI was compared with a high-end 12 GHz TDR/TDT
      system across a range of soils at varying soil water contents and densities. As
      propagation delay is the fundamental measurement of interest to the well
      established TDR or TDT technique; the first set of tests utilized precision
      propagation delay lines to test the accuracy of the SFI instrument's ability to
      resolve propagation delays across the expected range of delays that a soil probe
      would present when subjected to the expected range of soil types and soil
      moisture typical to an agronomic cropping system. The results of the precision
      delay line testing suggests the instrument is capable of predicting propagation
      delays with a RMSE of +/-105 ps across the range of delays ranging from 0 to
      12,000 ps with a coefficient of determination of r(2) = 0.998. The second phase
      of tests noted the rich history of TDR for prediction of soil moisture and
      leveraged this history by utilizing TDT measured with a high-end Hewlett Packard
      TDR/TDT instrument to directly benchmark the SFI instrument over a range of soil
      types, at varying levels of moisture. This testing protocol was developed to
      provide the best possible comparison between SFI to TDT than would otherwise be
      possible by using soil moisture as the bench mark, due to variations in soil
      density between soil water content levels which are known to impact the
      calibration between TDR's estimate of soil water content from the measured
      propagation delay which is converted to an apparent permittivity measurement.
      This experimental decision, to compare propagation delay of TDT to FDT,
      effectively removes the errors due to variations in packing density from the
      evaluation and provides a direct comparison between the SFI instrument and the
      time domain technique of TDT. The tests utilized three soils (a sand, an Acuff
      loam and an Olton clay-loam) that were packed to varying bulk densities and
      prepared to provide a range of water contents and electrical conductivities by
      which to compare the performance of the SFI technology to TDT measurements of
      propagation delay. For each sample tested, the SFI instrument and the TDT both
      performed the measurements on the exact same probe, thereby both instruments were
      measuring the exact same soil/soil-probe response to ensure the most accurate
      means to compare the SFI instrument to a high-end TDT instrument. Test results
      provided an estimated instrumental accuracy for the SFI of +/-0.98% of full
      scale, RMSE basis, for the precision delay lines and +/-1.32% when the SFI was
      evaluated on loam and clay loam soils, in comparison to TDT as the bench-mark.
      Results from both experiments provide evidence that the low-cost SFI approach is
      a viable alternative to conventional TDR/TDT for high accuracy applications.

PMID- 22368495
TI  - Local area water removal analysis of a proton exchange membrane fuel cell under
      gas purge conditions.
AB  - In this study, local area water content distribution under various gas purging
      conditions are experimentally analyzed for the first time. The local high
      frequency resistance (HFR) is measured using novel micro sensors. The results
      reveal that the liquid water removal rate in a membrane electrode assembly (MEA)
      is non-uniform. In the under-the-channel area, the removal of liquid water is
      governed by both convective and diffusive flux of the through-plane drying. Thus,
      almost all of the liquid water is removed within 30 s of purging with gas.
      However, liquid water that is stored in the under-the-rib area is not easy to
      remove during 1 min of gas purging. Therefore, the re-hydration of the membrane
      by internal diffusive flux is faster than that in the under-the-channel area.
      Consequently, local fuel starvation and membrane degradation can degrade the
      performance of a fuel cell that is started from cold.

PMID- 22368493
TI  - The evolution of the bacterial luciferase gene cassette (lux) as a real-time
      bioreporter.
AB  - The bacterial luciferase gene cassette (lux) is unique among bioluminescent
      bioreporter systems due to its ability to synthesize and/or scavenge all of the
      substrate compounds required for its production of light. As a result, the lux
      system has the unique ability to autonomously produce a luminescent signal,
      either continuously or in response to the presence of a specific trigger, across
      a wide array of organismal hosts. While originally employed extensively as a
      bacterial bioreporter system for the detection of specific chemical signals in
      environmental samples, the use of lux as a bioreporter technology has
      continuously expanded over the last 30 years to include expression in eukaryotic
      cells such as Saccharomyces cerevisiae and even human cell lines as well. Under
      these conditions, the lux system has been developed for use as a biomedical
      detection tool for toxicity screening and visualization of tumors in small animal
      models. As the technologies for lux signal detection continue to improve, it is
      poised to become one of the first fully implantable detection systems for intra
      organismal optical detection through direct marriage to an implantable photon
      detecting digital chip. This review presents the basic biochemical background
      that allows the lux system to continuously autobioluminesce and highlights the
      important milestones in the use of lux-based bioreporters as they have evolved
      from chemical detection platforms in prokaryotic bacteria to rodent-based
      tumorigenesis study targets. In addition, the future of lux imaging using
      integrated circuit microluminometry to image directly within a living host in
      real-time will be introduced and its role in the development of dose/response
      therapeutic systems will be highlighted.

PMID- 22368496
TI  - Smart sensor for real-time quantification of common symptoms present in unhealthy
      plants.
AB  - Plant responses to physiological function disorders are called symptoms and they
      are caused principally by pathogens and nutritional deficiencies. Plant symptoms
      are commonly used as indicators of the health and nutrition status of plants.
      Nowadays, the most popular method to quantify plant symptoms is based on visual
      estimations, consisting on evaluations that raters give based on their
      observation of plant symptoms; however, this method is inaccurate and imprecise
      because of its obvious subjectivity. Computational Vision has been employed in
      plant symptom quantification because of its accuracy and precision. Nevertheless,
      the systems developed so far lack in-situ, real-time and multi-symptom analysis.
      There exist methods to obtain information about the health and nutritional status
      of plants based on reflectance and chlorophyll fluorescence, but they use
      expensive equipment and are frequently destructive. Therefore, systems able of
      quantifying plant symptoms overcoming the aforementioned disadvantages that can
      serve as indicators of health and nutrition in plants are desirable. This paper
      reports an FPGA-based smart sensor able to perform non-destructive, real-time and
      in-situ analysis of leaf images to quantify multiple symptoms presented by
      diseased and malnourished plants; this system can serve as indicator of the
      health and nutrition in plants. The effectiveness of the proposed smart-sensor
      was successfully tested by analyzing diseased and malnourished plants.

PMID- 22368497
TI  - Reliability and availability evaluation of Wireless Sensor Networks for
      industrial applications.
AB  - Wireless Sensor Networks (WSN) currently represent the best candidate to be
      adopted as the communication solution for the last mile connection in process
      control and monitoring applications in industrial environments. Most of these
      applications have stringent dependability (reliability and availability)
      requirements, as a system failure may result in economic losses, put people in
      danger or lead to environmental damages. Among the different type of faults that
      can lead to a system failure, permanent faults on network devices have a major
      impact. They can hamper communications over long periods of time and consequently
      disturb, or even disable, control algorithms. The lack of a structured approach
      enabling the evaluation of permanent faults, prevents system designers to
      optimize decisions that minimize these occurrences. In this work we propose a
      methodology based on an automatic generation of a fault tree to evaluate the
      reliability and availability of Wireless Sensor Networks, when permanent faults
      occur on network devices. The proposal supports any topology, different levels of
      redundancy, network reconfigurations, criticality of devices and arbitrary
      failure conditions. The proposed methodology is particularly suitable for the
      design and validation of Wireless Sensor Networks when trying to optimize its
      reliability and availability requirements.

PMID- 22368498
TI  - A low-complexity geometric bilateration method for localization in Wireless
      Sensor Networks and its comparison with Least-Squares methods.
AB  - This research presents a distributed and formula-based bilateration algorithm
      that can be used to provide initial set of locations. In this scheme each node
      uses distance estimates to anchors to solve a set of circle-circle intersection
      (CCI) problems, solved through a purely geometric formulation. The resulting CCIs
      are processed to pick those that cluster together and then take the average to
      produce an initial node location. The algorithm is compared in terms of accuracy
      and computational complexity with a Least-Squares localization algorithm, based
      on the Levenberg-Marquardt methodology. Results in accuracy vs. computational
      performance show that the bilateration algorithm is competitive compared with
      well known optimized localization algorithms.

PMID- 22368499
TI  - Real time corner detection for miniaturized electro-optical sensors onboard small
      unmanned aerial systems.
AB  - This paper describes the target detection algorithm for the image processor of a
      vision-based system that is installed onboard an unmanned helicopter. It has been
      developed in the framework of a project of the French national aerospace research
      center Office National d'Etudes et de Recherches Aerospatiales (ONERA) which aims
      at developing an air-to-ground target tracking mission in an unknown urban
      environment. In particular, the image processor must detect targets and estimate
      ground motion in proximity of the detected target position. Concerning the target
      detection function, the analysis has dealt with realizing a corner detection
      algorithm and selecting the best choices in terms of edge detection methods,
      filtering size and type and the more suitable criterion of detection of the
      points of interest in order to obtain a very fast algorithm which fulfills the
      computation load requirements. The compared criteria are the Harris-Stephen and
      the Shi-Tomasi, ones, which are the most widely used in literature among those
      based on intensity. Experimental results which illustrate the performance of the
      developed algorithm and demonstrate that the detection time is fully compliant
      with the requirements of the real-time system are discussed.

PMID- 22368500
TI  - Paper withdrawn before issue release. "Juan V. Capella, Alberto Bonastre, Miguel
      Peris and Rafael Ors. Distributed in-line analysis of water pollution in a
      Spanish lake.Sensors 2012, 12, 878-894".

PMID- 22368501
TI  - Phantom with pulsatile arteries to investigate the influence of blood vessel
      depth on pulse oximeter signal strength.
AB  - This paper describes a three-layer head phantom with artificial pulsating
      arteries at five different depths (1.2 mm, 3.7 mm, 6.8 mm, 9.6 mm and 11.8 mm).
      The structure enables formation of spatially and temporally varying tissue
      properties similar to those of living tissues. In our experiment, pressure pulses
      were generated in the arteries by an electronically controlled pump. The physical
      and optical parameters of the layers and the liquid in the artificial arteries
      were similar to those of real tissues and blood. The amplitude of the pulsating
      component of the light returning from the phantom tissues was measured at each
      artery depth mentioned above. The build-up of the in-house-developed pulse
      oximeter used for performing the measurements and the physical layout of the
      measuring head are described. The radiant flux generated by the LED on the
      measuring head was measured to be 1.8 mW at 910 nm. The backscattered radiant
      flux was measured, and found to be 0.46 nW (0.26 ppm), 0.55 nW (0.31 ppm), and
      0.18 nW (0.10 ppm) for the 1.2 mm, 3.7 mm and 6.8 mm arteries, respectively. In
      the case of the 9.6 mm and 11.8 mm arteries, useful measurement data were not
      obtained owing to weak signals. We simulated the phantom with the arteries at the
      above-mentioned five depths and at two additional ones (2.5 mm and 5.3 mm in
      depth) using the Monte Carlo method. The measurement results were verified by the
      simulation results. We concluded that in case of 11 mm source-detector separation
      the arteries at a depth of about 2.5 mm generate the strongest pulse oximeter
      signal level in a tissue system comprising three layers of thicknesses: 1.5 mm
      (skin), 5.0 mm (skull), and >50 mm (brain).

PMID- 22368502
TI  - Sheathless size-based acoustic particle separation.
AB  - Particle separation is of great interest in many biological and biomedical
      applications. Flow-based methods have been used to sort particles and cells.
      However, the main challenge with flow based particle separation systems is the
      need for a sheath flow for successful operation. Existence of the sheath liquid
      dilutes the analyte, necessitates precise flow control between sample and sheath
      flow, requires a complicated design to create sheath flow and separation
      efficiency depends on the sheath liquid composition. In this paper, we present a
      microfluidic platform for sheathless particle separation using standing surface
      acoustic waves. In this platform, particles are first lined up at the center of
      the channel without introducing any external sheath flow. The particles are then
      entered into the second stage where particles are driven towards the off-center
      pressure nodes for size based separation. The larger particles are exposed to
      more lateral displacement in the channel due to the acoustic force differences.
      Consequently, different-size particles are separated into multiple collection
      outlets. The prominent feature of the present microfluidic platform is that the
      device does not require the use of the sheath flow for positioning and aligning
      of particles. Instead, the sheathless flow focusing and separation are integrated
      within a single microfluidic device and accomplished simultaneously. In this
      paper, we demonstrated two different particle size-resolution separations; (1) 3
      MUm and 10 MUm and (2) 3 MUm and 5 MUm. Also, the effects of the input power, the
      flow rate, and particle concentration on the separation efficiency were
      investigated. These technologies have potential to impact broadly various areas
      including the essential microfluidic components for lab-on-a-chip system and
      integrated biological and biomedical applications.

PMID- 22368504
TI  - Sap flow sensors: construction, quality control and comparison.
AB  - This work provides a design for two types of sensors, based on the thermal
      dissipation and heat ratio methods of sap flow calculation, for moderate to large
      scale deployments for the purpose of monitoring tree transpiration. These designs
      include a procedure for making these sensors, a quality control method for the
      final products, and a complete list of components with vendors and pricing
      information. Both sensor designs were field tested alongside a commercial sap
      flow sensor to assess their performance and show the importance for quality
      controlling the sensor outputs. Results show that for roughly 2% of the cost of
      commercial sensors, self-made sap flow sensors can provide acceptable estimates
      of the sap flow measurements compared to the commercial sensors.

PMID- 22368503
TI  - Recent advances in polymeric materials used as electron mediators and
      immobilizing matrices in developing enzyme electrodes.
AB  - Different classes of polymeric materials such as nanomaterials, sol-gel
      materials, conducting polymers, functional polymers and biomaterials have been
      used in the design of sensors and biosensors. Various methods have been used, for
      example from direct adsorption, covalent bonding, crossing-linking with
      glutaraldehyde on composites to mixing the enzymes or use of functionalized beads
      for the design of sensors and biosensors using these polymeric materials in
      recent years. It is widely acknowledged that analytical sensing at electrodes
      modified with polymeric materials results in low detection limits, high
      sensitivities, lower applied potential, good stability, efficient electron
      transfer and easier immobilization of enzymes on electrodes such that sensing and
      biosensing of environmental pollutants is made easier. However, there are a
      number of challenges to be addressed in order to fulfill the applications of
      polymeric based polymers such as cost and shortening the long laboratory
      synthetic pathways involved in sensor preparation. Furthermore, the toxicological
      effects on flora and fauna of some of these polymeric materials have not been
      well studied. Given these disadvantages, efforts are now geared towards
      introducing low cost biomaterials that can serve as alternatives for the
      development of novel electrochemical sensors and biosensors. This review
      highlights recent contributions in the development of the electrochemical sensors
      and biosensors based on different polymeric material. The synergistic action of
      some of these polymeric materials and nanocomposites imposed when combined on
      electrode during sensing is discussed.

PMID- 22368505
TI  - Prediction of BOD, COD, and total nitrogen concentrations in a typical urban
      river using a fluorescence excitation-emission matrix with PARAFAC and UV
      absorption indices.
AB  - The development of a real-time monitoring tool for the estimation of water
      quality is essential for efficient management of river pollution in urban areas.
      The Gap River in Korea is a typical urban river, which is affected by the
      effluent of a wastewater treatment plant (WWTP) and various anthropogenic
      activities. In this study, fluorescence excitation-emission matrices (EEM) with
      parallel factor analysis (PARAFAC) and UV absorption values at 220 nm and 254 nm
      were applied to evaluate the estimation capabilities for biochemical oxygen
      demand (BOD), chemical oxygen demand (COD), and total nitrogen (TN)
      concentrations of the river samples. Three components were successfully
      identified by the PARAFAC modeling from the fluorescence EEM data, in which each
      fluorophore group represents microbial humic-like (C1), terrestrial humic-like
      organic substances (C2), and protein-like organic substances (C3), and UV
      absorption indices (UV(220) and UV(254)), and the score values of the three
      PARAFAC components were selected as the estimation parameters for the nitrogen
      and the organic pollution of the river samples. Among the selected indices,
      UV(220), C3 and C1 exhibited the highest correlation coefficients with BOD, COD,
      and TN concentrations, respectively. Multiple regression analysis using UV(220)
      and C3 demonstrated the enhancement of the prediction capability for TN.

PMID- 22368506
TI  - Transformation of hand-shape features for a biometric identification approach.
AB  - The present work presents a biometric identification system for hand shape
      identification. The different contours have been coded based on angular
      descriptions forming a Markov chain descriptor. Discrete Hidden Markov Models
      (DHMM), each representing a target identification class, have been trained with
      such chains. Features have been calculated from a kernel based on the HMM
      parameter descriptors. Finally, supervised Support Vector Machines were used to
      classify parameters from the DHMM kernel. First, the system was modelled using 60
      users to tune the DHMM and DHMM_kernel+SVM configuration parameters and finally,
      the system was checked with the whole database (GPDS database, 144 users with 10
      samples per class). Our experiments have obtained similar results in both cases,
      demonstrating a scalable, stable and robust system. Our experiments have achieved
      an upper success rate of 99.87% for the GPDS database using three hand samples
      per class in training mode, and seven hand samples in test mode. Secondly, the
      authors have verified their algorithms using another independent and public
      database (the UST database). Our approach has reached 100% and 99.92% success for
      right and left hand, respectively; showing the robustness and independence of our
      algorithms. This success was found using as features the transformation of 100
      points hand shape with our DHMM kernel, and as classifier Support Vector Machines
      with linear separating functions, with similar success.

PMID- 22368507
TI  - FBG sensor for contact level monitoring and prediction of perforation in cardiac
      ablation.
AB  - Atrial fibrillation (AF) is the most common type of arrhythmia, and is
      characterized by a disordered contractile activity of the atria (top chambers of
      the heart). A popular treatment for AF is radiofrequency (RF) ablation. In about
      2.4% of cardiac RF ablation procedures, the catheter is accidently pushed through
      the heart wall due to the application of excessive force. Despite the various
      capabilities of currently available technology, there has yet to be any data
      establishing how cardiac perforation can be reliably predicted. Thus, two new FBG
      based sensor prototypes were developed to monitor contact levels and predict
      perforation. Two live sheep were utilized during the study. It was observed
      during operation that peaks appeared in rhythm with the heart rate whenever firm
      contact was made between the sensor and the endocardial wall. The magnitude of
      these peaks varied with pressure applied by the operator. Lastly, transmural
      perforation of the left atrial wall was characterized by a visible loading phase
      and a rapid signal drop-off correlating to perforation. A possible pre
      perforation signal was observed for the epoxy-based sensor in the form of a
      slight signal reversal (12-26% of loading phase magnitude) prior to perforation
      (occurring over 8 s).

PMID- 22368508
TI  - Optimal methods of RTK-GPS/accelerometer integration to monitor the displacement
      of structures.
AB  - The accurate measurement of diverse displacements of structures is an important
      index for the evaluation of a structure's safety. In this study, a comparative
      analysis was conducted to determine the integrated RTK-GPS/accelerometer method
      that can provide the most precise structure displacement measurements. For this
      purpose, three methods of calculating the dynamic displacements from the
      acceleration data were comparatively analyzed. In addition, two methods of
      determining dynamic, static, and quasi-static displacements by integrating the
      displacements measured from the RTK-GPS system and the accelerometer were also
      comparatively analyzed. To ensure precise comparison results, a cantilever beam
      was manufactured onto which diverse types of displacements were generated to
      evaluate the measurement accuracy by method. Linear variable differential
      transformer (LVDT) measurements were used as references for the evaluation to
      ensure accuracy. The study results showed that the most suitable method of
      measuring the dynamic displacement with the accelerometer was to calculate the
      displacement by filtering and double-integrating the acceleration data using the
      FIR band-pass filter. The integration method that uses frequency-based
      displacement extraction was most appropriate for the integrated RTK
      GPS/accelerometer method of comprehensively measuring the dynamic, static, and
      quasi-static displacements.

PMID- 22368509
TI  - Post-synapse model cell for synaptic glutamate receptor (GluR)-based biosensing:
      strategy and engineering to maximize ligand-gated ion-flux achieving high signal
      to-noise ratio.
AB  - Cell-based biosensing is a "smart" way to obtain efficacy-information on the
      effect of applied chemical on cellular biological cascade. We have proposed an
      engineered post-synapse model cell-based biosensors to investigate the effects of
      chemicals on ionotropic glutamate receptor (GluR), which is a focus of attention
      as a molecular target for clinical neural drug discovery. The engineered model
      cell has several advantages over native cells, including improved ease of
      handling and better reproducibility in the application of cell-based biosensors.
      However, in general, cell-based biosensors often have low signal-to-noise (S/N)
      ratios due to the low level of cellular responses. In order to obtain a higher
      S/N ratio in model cells, we have attempted to design a tactic model cell with
      elevated cellular response. We have revealed that the increase GluR expression
      level is not directly connected to the amplification of cellular responses
      because the saturation of surface expression of GluR, leading to a limit on the
      total ion influx. Furthermore, coexpression of GluR with a voltage-gated
      potassium channel increased Ca(2+) ion influx beyond levels obtained with
      saturating amounts of GluR alone. The construction of model cells based on
      strategy of amplifying ion flux per individual receptors can be used to perform
      smart cell-based biosensing with an improved S/N ratio.

PMID- 22368510
TI  - Electronic voltage and current transformers testing device.
AB  - A method for testing electronic instrument transformers is described, including
      electronic voltage and current transformers (EVTs, ECTs) with both analog and
      digital outputs. A testing device prototype is developed. It is based on digital
      signal processing of the signals that are measured at the secondary outputs of
      the tested transformer and the reference transformer when the same excitation
      signal is fed to their primaries. The test that estimates the performance of the
      prototype has been carried out at the National Centre for High Voltage
      Measurement and the prototype is approved for testing transformers with precision
      class up to 0.2 at the industrial frequency (50 Hz or 60 Hz). The device is
      suitable for on-site testing due to its high accuracy, simple structure and low
      cost hardware.

PMID- 22368511
TI  - Computer reconstruction of plant growth and chlorophyll fluorescence emission in
      three spatial dimensions.
AB  - Plant leaves grow and change their orientation as well their emission of
      chlorophyll fluorescence in time. All these dynamic plant properties can be semi
      automatically monitored by a 3D imaging system that generates plant models by the
      method of coded light illumination, fluorescence imaging and computer 3D
      reconstruction. Here, we describe the essentials of the method, as well as the
      system hardware. We show that the technique can reconstruct, with a high
      fidelity, the leaf size, the leaf angle and the plant height. The method fails
      with wilted plants when leaves overlap obscuring their true area. This effect,
      naturally, also interferes when the method is applied to measure plant growth
      under water stress. The method is, however, very potent in capturing the plant
      dynamics under mild stress and without stress. The 3D reconstruction is also
      highly effective in correcting geometrical factors that distort measurements of
      chlorophyll fluorescence emission of naturally positioned plant leaves.

PMID- 22368512
TI  - Activity inference for Ambient Intelligence through handling artifacts in a
      healthcare environment.
AB  - Human activity inference is not a simple process due to distinct ways of
      performing it. Our proposal presents the SCAN framework for activity inference.
      SCAN is divided into three modules: (1) artifact recognition, (2) activity
      inference, and (3) activity representation, integrating three important elements
      of Ambient Intelligence (AmI) (artifact-behavior modeling, event interpretation
      and context extraction). The framework extends the roaming beat (RB) concept by
      obtaining the representation using three kinds of technologies for activity
      inference. The RB is based on both analysis and recognition from artifact
      behavior for activity inference. A practical case is shown in a nursing home
      where a system affording 91.35% effectiveness was implemented in situ. Three
      examples are shown using RB representation for activity representation. Framework
      description, RB description and CALog system overcome distinct problems such as
      the feasibility to implement AmI systems, and to show the feasibility for
      accomplishing the challenges related to activity recognition based on artifact
      recognition. We discuss how the use of RBs might positively impact the problems
      faced by designers and developers for recovering information in an easier manner
      and thus they can develop tools focused on the user.

PMID- 22368513
TI  - Pre-processing of point-data from contact and optical 3D digitization sensors.
AB  - Contemporary 3D digitization systems employed by reverse engineering (RE) feature
      ever-growing scanning speeds with the ability to generate large quantity of
      points in a unit of time. Although advantageous for the quality and efficiency of
      RE modelling, the huge number of point datas can turn into a serious practical
      problem, later on, when the CAD model is generated. In addition, 3D digitization
      processes are very often plagued by measuring errors, which can be attributed to
      the very nature of measuring systems, various characteristics of the digitized
      objects and subjective errors by the operator, which also contribute to problems
      in the CAD model generation process. This paper presents an integral system for
      the pre-processing of point data, i.e., filtering, smoothing and reduction, based
      on a cross-sectional RE approach. In the course of the proposed system
      development, major emphasis was placed on the module for point data reduction,
      which was designed according to a novel approach with integrated deviation
      analysis and fuzzy logic reasoning. The developed system was verified through its
      application on three case studies, on point data from objects of versatile
      geometries obtained by contact and laser 3D digitization systems. The obtained
      results demonstrate the effectiveness of the system.

PMID- 22368515
TI  - Role of chemokine receptor CXCR2 expression in mammary tumor growth, angiogenesis
      and metastasis.
AB  - BACKGROUND: Chemokines and their receptors have long been known to regulate
      metastasis in various cancers. Previous studies have shown that CXCR2 expression
      is upregulated in malignant breast cancer tissues but not in benign ductal
      epithelial samples. The functional role of CXCR2 in the metastatic phenotype of
      breast cancer still remains unclear. We hypothesize that the chemokine receptor,
      CXCR2, mediates tumor cell invasion and migration and promotes metastasis in
      breast cancer. The objective of this study is to investigate the potential role
      of CXCR2 in the metastatic phenotype of mouse mammary tumor cells. MATERIALS AND
      METHODS: We evaluated the functional role of CXCR2 in breast cancer by stably
      downregulating the expression of CXCR2 in metastatic mammary tumor cell lines
      Cl66 and 4T1, using short hairpin RNA (shRNA). The effects of CXCR2
      downregulation on tumor growth, invasion and metastatic potential were analyzed
      in vitro and in vivo. RESULTS: We demonstrated knock down of CXCR2 in Cl66 and
      4T1 cells (Cl66-shCXCR2 and 4T1-shCXCR2) cells by reverse transcriptase
      polymerase chain reaction (RT-PCR) at the transcriptional level and by
      immunohistochemistry at the protein level. We did not observe a significant
      difference in in vitro cell proliferation between vector control and CXCR2 knock
      down Cl66 or 4T1 cells. Next, we examined the invasive potential of Cl66-shCXCR2
      cells by in vitro Matrigel invasion assay. We observed a significantly lower
      number (52 +/- 5) of Cl66-shCXCR2 cells invading through Matrigel compared to
      control cells (Cl66-control) (182 +/- 3) (P < 0.05). We analyzed the in vivo
      metastatic potential of Cl66-shCXCR2 using a spontaneous metastasis model by
      orthotopically implanting cells into the mammary fat pad of female BALB/c mice.
      Animals were sacrificed 12 weeks post tumor implantation and tissue samples were
      analyzed for metastatic nodules. CXCR2 downregulation significantly inhibited
      tumor cell metastasis. All the mice (n = 10) implanted with control Cl66 cells
      spontaneously developed lung metastasis, whereas a significantly lower number of
      mice (40%) implanted with Cl66-shCXCR2 cells exhibited lung metastases.
      CONCLUSIONS: Together, these results suggest that CXCR2 may play a critical role
      in breast cancer invasion and metastasis.

PMID- 22368516
TI  - Comparative metabolism of benzo[a]pyrene by human keratinocytes infected with
      high-risk human papillomavirus types 16 and 18 as episomal or integrated genomes.
AB  - BACKGROUND: Infection with human papillomavirus (HPV) is a critical factor in the
      development of cervical cancer. Smoking is an additional risk factor. Tobacco
      smoke carcinogens, such as benzo[a]pyrene (B[a]P), and their cytochrome P450
      related metabolites are present in significantly higher levels in the cervical
      mucus of women smokers than in nonsmokers. We determined the metabolism and P450
      expression of B[a]P-treated human keratinocytes infected with HPV-16 or -18.
      MATERIALS AND METHODS: Monolayer cultures of uninfected primary human foreskin
      keratinocytes, human vaginal and cervical keratinocytes carrying episomal genomes
      of HPV-16 and -18, respectively, and invasive cervical carcinoma cell lines
      carrying either HPV-16 or -18 genomes integrated into the host DNA, were
      incubated with 0.1 MUM [(3)H]B[a]P. The resulting oxidative metabolites were
      analyzed and quantified by radioflow high-performance liquid chromatography.
      Additionally, all cell lines were incubated with unlabeled 0.1 MUM B[a]P for
      Western blot analysis of cytochrome P450 1A1 and 1B1. RESULTS: Significant
      enhancement in levels of both detoxification and activation metabolites was found
      in incubations with all types of HPV-infected cells compared with control
      incubations (P < 0.05). The highest capacity to metabolize B[a]P was observed
      with cells containing integrated HPV-18 genomes. Induction of cytochrome 1B1 was
      observed in HPV-16 and -18 integrated, and in HPV-16 episomal cell types.
      CONCLUSIONS: Both viral genotype and genomic status in the host cell affect B[a]P
      metabolism and cytochrome P450 1B1 expression. An increase of DNA-damaging
      metabolites might result from exposure of HPV-infected women to cigarette smoke
      carcinogens.

PMID- 22368517
TI  - Changes in Affect and Drinking Outcomes in a Pharmacobehavioral Trial for Alcohol
      Dependence.
AB  - OBJECTIVE: Despite extensive research exploring affect in alcohol dependent
      individuals in recovery, empirical research on affective changes over the course
      of psychosocial treatment and their role on drinking outcomes has been minimal.
      The present study examined the relationship between changes in positive affect
      (PA), negative affect (NA), and drinking outcomes during a pharmacobehavioral
      trial.  METHOD: Data for these post-hoc exploratory analyses were derived from a
      clinical trial of 321 alcohol dependent male and female individuals. The study
      design had four treatment arms for medication: three levels of dose of
      ondansetron as well as a control condition (placebo). All participants received
      weekly cognitive behavioral therapy for twelve weeks. We conducted an exploratory
      evaluation of changes in negative and positive affect and drinking behavior over
      time during the treatment phase of the trial using multilevel modeling.  RESULTS:
      Participants experienced substantial reductions in drinking, decreases in NA, and
      increases in PA over the course of treatment. Individuals who experienced
      increases in PA over the course of treatment significantly reduced their drinking
      in subsequent weeks, while those who had reductions in NA only experienced
      reductions in drinking later in treatment if they also reported increases in PA.
      These results support the role of affect regulation in treatment.  CONCLUSIONS:
      These results suggest that affective change during the course of treatment may
      serve as one potential mechanism of action for changes in drinking behavior. The
      interaction between reductions in NA and increases in PA may be particularly
      important in promoting new coping skills and reducing drinking.

PMID- 22368518
TI  - Inflammation and epilepsy: the foundations for a new therapeutic approach in
      epilepsy?
AB  - Emerging data from experimental epilepsy models and resected human brain tissue
      support the proposed involvement of innate immune system activation and
      consequent inflammation in epilepsy. Key mediators of this process include
      interleukin-1beta, high-mobility group box protein 1 (HMGB1), and Toll-like
      receptor (TLR) signaling. These recent findings constitute the basis for a novel
      avenue of drug development in epilepsy, one that is not only distinct from
      previous approaches but uniquely based on sound neurobiological evidence.

PMID- 22368519
TI  - Is Intrinsic Hyperexcitability in CA3 the Culprit for Seizures in Rett Syndrome?

PMID- 22368520
TI  - A Tuber-ful Animal Model of Tuberous Sclerosis At Last?

PMID- 22368521
TI  - CLC-3 Takes a Quantum Leap Toward Understanding Mechanisms of GABA Release.

PMID- 22368522
TI  - Adenosine: a fundamental factor formed from Fatty feasts for fighting fits?

PMID- 22368523
TI  - Dephosphorylation proves detrimental to GABAergic inhibition.

PMID- 22368524
TI  - Trial Design: How Do We Figure Out if an AED Works.
AB  - Regulatory trials rigorously test the ability of a treatment to impact a known
      outcome, such as seizure frequency, as measured in well-controlled trials. Such
      outcomes are called efficacy outcomes. Sometimes these measured outcomes do not
      reflect the true effectiveness of the drug in the clinic. This article provides
      some examples of how this can happen and also discusses trials intended to
      measure effectiveness.

PMID- 22368525
TI  - Ezogabine AKA Retigabine: Is More Better? Trying to Find the Right Dose From
      Clinical Trials.

PMID- 22368526
TI  - Do We Need EEGs After Temporal Lobe Epilepsy Surgery, and How Many?

PMID- 22368527
TI  - Generic antiepileptic drugs: how good is close enough?

PMID- 22368528
TI  - Imaging focal cortical dysplasia in refractory epilepsy.

PMID- 22368529
TI  - Epilepsy surgery and postoperative depression: charting difficult territory.

PMID- 22368530
TI  - Conformational Transitions and Convergence of Absolute Binding Free Energy
      Calculations.
AB  - The Binding Energy Distribution Analysis Method (BEDAM) is employed to compute
      the standard binding free energies of a series of ligands to a FK506 binding
      protein (FKBP12) with implicit solvation. Binding free energy estimates are in
      reasonably good agreement with experimental affinities. The conformations of the
      complexes identified by the simulations are in good agreement with
      crystallographic data, which was not used to restrain ligand orientations. The
      BEDAM method is based on lambda -hopping Hamiltonian parallel Replica Exchange
      (HREM) molecular dynamics conformational sampling, the OPLS-AA/AGBNP2 effective
      potential, and multi-state free energy estimators (MBAR). Achieving converged and
      accurate results depends on all of these elements of the calculation. Convergence
      of the binding free energy is tied to the level of convergence of binding energy
      distributions at critical intermediate states where bound and unbound states are
      at equilibrium, and where the rate of binding/unbinding conformational
      transitions is maximal. This finding mirrors similar observations in the context
      of order/disorder transitions as for example in protein folding. Insights
      concerning the physical mechanism of ligand binding and unbinding are obtained.
      Convergence for the largest FK506 ligand is achieved only after imposing strict
      conformational restraints, which however require accurate prior structural
      knowledge of the structure of the complex. The analytical AGBNP2 model is found
      to underestimate the magnitude of the hydrophobic driving force towards binding
      in these systems characterized by loosely packed protein-ligand binding
      interfaces. Rescoring of the binding energies using a numerical surface area
      model corrects this deficiency. This study illustrates the complex interplay
      between energy models, exploration of conformational space, and free energy
      estimators needed to obtain robust estimates from binding free energy
      calculations.

PMID- 22368532
TI  - Service Utilization Patterns as Predictors of Response to Trauma-Informed
      Integrated Treatment for Women With Co-occurring Disorders.
AB  - OBJECTIVE: The current study examined whether clinical responses to an integrated
      treatment intervention among women with co-occurring disorders and histories of
      abuse varied according to their service use patterns at baseline.  METHODS: Data
      were from a national, multi-site, integrated treatment intervention study in 1998
      2003. Analyses included 999 study participants assigned to the integrated
      treatment group and who were symptomatic at baseline. Participants' baseline
      service use activity was characterized according to five distinct baseline
      service use clusters. Logistic regression models estimated study participants'
      odds of good clinical responses to integrated treatment at 12 months across the
      five service clusters.  RESULTS: Participants with high levels of psychotropic
      medication and medical care use at baseline had significantly lower odds than low
      intensity service users of having a good response to integrated treatment at 12
      months on mental health, alcohol addiction, and posttraumatic stress measures. A
      majority of women in this group had serious medical illness or disability and
      were more likely than their counterparts with other service use patterns to have
      used homeless or domestic violence shelters.  CONCLUSIONS: Women who used high
      levels of medication and medical services appear to have faced especially
      difficult barriers in responding well to integrated treatment. Careful
      assessments of their mental health, trauma, and medical treatment needs may be
      required as part of integrated treatment in an effort to improve their response
      to integrated treatment, clinical outcomes and well-being. This information can
      also be used to target integrated treatment to women who are likely to respond
      positively and achieve meaningful improvements in their functioning.

PMID- 22368531
TI  - Optimization of the CHARMM additive force field for DNA: Improved treatment of
      the BI/BII conformational equilibrium.
AB  - The B-form of DNA can populate two different backbone conformations: BI and BII,
      defined by the difference between the torsion angles epsilon and zeta (BI =
      epsilon-zeta < 0 and BII = epsilon-zeta > 0). BI is the most populated state, but
      the population of the BII state, which is sequence dependent, is significant and
      accumulating evidence shows that BII affects the overall structure of DNA, and
      thus influences protein-DNA recognition. This work presents a reparametrization
      of the CHARMM27 additive nucleic acid force field to increase the sampling of the
      BII form in MD simulations of DNA. In addition, minor modifications of sugar
      puckering were introduced to facilitate sampling of the A form of DNA under the
      appropriate environmental conditions. Parameter optimization was guided by
      quantum mechanical data on model compounds, followed by calculations on several
      DNA duplexes in the condensed phase. The selected optimized parameters were then
      validated against a number of DNA duplexes, with the most extensive tests
      performed on the EcoRI dodecamer, including comparative calculations using the
      Amber Parm99bsc0 force field. The new CHARMM model better reproduces
      experimentally observed sampling of the BII conformation, including sampling as a
      function of sequence. In addition, the model reproduces the A form of the 1ZF1
      duplex in 75 % ethanol, and yields a stable Z-DNA conformation of duplex
      (GTACGTAC) in its crystal environment. The resulting model, in combination with a
      recent reoptimization of the CHARMM27 force field for RNA, will be referred to as
      CHARMM36.

PMID- 22368533
TI  - Use of Theoretical Frameworks as a Pragmatic Guide for Mixed Methods Studies: A
      Methodological Necessity?
AB  - There is a growing acceptance of the utility of mixed methods in health sciences
      but there is no widely accepted set of ideas in regard to use of a conceptual or
      theoretical framework to guide inquiry. Few mixed methods health science articles
      report the use of such a framework. Lack of available conceptual maps provided by
      theoretical frameworks, necessary intricacy of design, and the qualitative "black
      box" tradition all contribute to a dearth of methodological guidance in such
      studies. This article uses a funded National Institutes of Health study as an
      example to explain the utility of a theoretical framework in conceptualizing a
      study, making design decisions such as sampling and recruitment, collecting and
      analyzing data, and data interpretation.

PMID- 22368534
TI  - A molecular, morphological and ecological re-appraisal of Venturiales-a new order
      of Dothideomycetes.
AB  - The Venturiaceae was traditionally assigned to Pleosporales although its
      diagnostic characters readily distinguish it from other pleosporalean families.
      These include a parasitic or saprobic lifestyle, occurring on leaves or stems of
      dicotyledons; small to medium-sized ascomata, often with setae; deliquescing
      pseudoparaphyses; 8-spored, broadly cylindrical to obclavate asci; 1-septate,
      yellowish, greenish or pale brown to brown ascospores; and hyphomycetous
      anamorphs. Phylogenetically, core genera of Venturiaceae form a monophyletic
      clade within Dothideomycetes, and represent a separate sister lineage from
      current orders, thus a new order-Venturiales is introduced. A new family,
      Sympoventuriaceae, is introduced to accommodate taxa of a well-supported subclade
      within Venturiales, which contains Sympoventuria, Veronaeopsis simplex and
      Fusicladium-like species. Based on morphology and DNA sequence analysis, eight
      genera are included in Venturiaceae, viz. Acantharia, Apiosporina (including
      Dibotryon), Caproventuria, Coleroa, Pseudoparodiella, Metacoleroa, Tyrannosorus
      and Venturia. Molecular phylogenetic information is lacking for seven genera
      previously included in Venturiales, namely Arkoola, Atopospora, Botryostroma,
      Lasiobotrys, Trichodothella, Trichodothis and Rhizogenee and these are discussed,
      but their inclusion in Venturiaceae is doubtful. Crotone, Gibbera, Lineostroma,
      Phaeocryptopus, Phragmogibbera, Platychora, Polyrhizon, Rosenscheldiella,
      Uleodothis and Xenomeris are excluded from Venturiales, and their ordinal
      placement needs further investigation. Zeuctomorpha is treated as a synonym of
      Acantharia.

PMID- 22368535
TI  - ?
AB  - The electrocarboxylation of a series of benzophenones under galvanostatic
      conditions has been carried out in aprotic solvents using an undivided bulk
      electrolysis cell equipped with a Mg sacrificial anode. Systematic studies have
      been carried out in order to establish the qualitative relationships between the
      yield of carboxylation reaction and the operational and intrinsic parameters for
      the electrocarboxylation of benzophenones. For the diaryl ketones chosen for
      these studies, the yields of the target benzilic acids have been found to be
      strongly dependent on different parameters such as solvents, supporting
      electrolytes, cathode materials, current density, temperature and the nature of
      the substrates.

PMID- 22368536
TI  - A new venture from an old medical school.

PMID- 22368537
TI  - Interpretation of electrocardiograms in infants and children.
AB  - Electrocardiography is a useful tool in the management of paediatric heart
      disease. Interpretation requires practice due to changing norms which are brought
      about by the physiological changes that occur in the circulatory system in this
      age group. This article outlines these normal changes.

PMID- 22368538
TI  - World wide web and scientific publishing.
AB  - The relationship of scientific publishing and the world wide web steadily evolves
      as the internet technology advances in its sophistication and ability to reach an
      increasing number of people. Many well established medical publication currently
      publish their journal electronically as well as in print format. Forced by high
      volume of manuscript submissions as well as financial restraints, some journals
      publish a number of their articles on the internet alone, while others-such as
      this journal-are starting an entirely new publication in an electronic version
      only. The presentation of articles in the field of pediatric cardiology
      electronically has numerous advantages, particularly the ability to include movie
      clips, sound and animations in the published articles. This format of publication
      continues to have limitation. It is still not as widely available as a print
      journal could be and it is awkward to curl up in bed with a lap top, no matter
      how small or light it is.

PMID- 22368539
TI  - Cardiac illustrations.
AB  - Pictures of congenital heart lesions are very useful for patient and parent
      understanding of underlying problems, and the actual physical mechanics of
      treatment/s, both past and proposed. In this article, we have produced scanned
      pictures by Heartline from their book 'Heart Children'. We have also added some
      new graphics that depict heart lesions not originally in this book, and in
      addition, some postoperative situations. Heartline.

PMID- 22368540
TI  - Concepts in cardiology - a historical perspective.
AB  - Our current knowledge of the anatomy and physiology of the circulatory system has
      been reached by deduction and reasoning over several centuries. In this article,
      we briefly outline the history of these theories.

PMID- 22368541
TI  - Central venous catheters in children and neonates (Part 2) - Access via the
      internal jugular vein.
AB  - Central venous access via the internal jugular vein (IJV) is safe, relatively
      easy and very commonly used in infants and children undergoing cardiac surgery
      for congenital heart disease. Because of the wide range of anatomical variations
      an ultrasound-guided technique is advantageous in many cases, in particular in
      patients who have had previous punctures or those in whom difficulties are
      anticipated for various reasons. The right internal jugular vein is the preferred
      vein for central venous access as it offers straight access to the superior vena
      cava. The rate of complications - insertion-related as well as long term - are
      lower compared to the femoral and the subclavian access.

PMID- 22368542
TI  - Coil occlusion of the large patent ductus arteriosus.
AB  - While coil occlusion is well accepted for the small patent ductus arteriosus
      (PDA), occlusive devices are preferred for the larger (> 3 mm) ducts by most
      institutions. Because of costs concerns, occlusive devices are not always
      realistic in many countries. The technique of simultaneous delivery of multiple
      coils with bioptome assistance works well for relatively larger ducts. This
      technique requires careful case selection through echocardiography. The duct
      anatomy plays a crucial part in determining the suitability for coil occlusion.
      Coil occlusion has a specific advantage for relatively larger ducts in selected
      small children and in preterm infants because it is possible to accomplish
      delivery of multiple coils through relatively small introducer sheaths. In
      addition, aortic narrowing is less likely because coils compact in the ampulla.
      This review describes case selection strategies and techniques of coil occlusion
      of the large PDA. Relevant illustrative images are shown.

PMID- 22368543
TI  - Morphology of the patent arterial duct: features relevant to treatment.
AB  - Patent ductus arteriosus (PDA), one of the most common congenital heart defects,
      is an abnormal persistence of a patent lumen in the arterial duct due to an
      arrest of the natural process of closure after it has served its function as a
      vital channel in fetal circulation. The histological feature of the arterial duct
      is entirely different from its adjoining arteries and many intrinsic substances
      mediate in the process of its normal closure. When existing in isolation,
      catheter or surgical intervention is usually used for its treatment. Ductal
      aneurysm is a rare type of PDA. The PDA associated with other congenital heart
      disease has variable morphology and closing it naturally or by intervention may
      produce critical symptoms. The PDA and its ligament which represents a closed
      arterial duct can be part of a vascular ring with abnormal aortic arch formation.
      It is important to understand the morphological features of PDA so as to choose
      the optimal strategy for treatment.

PMID- 22368544
TI  - Unusual echocardiographic finding leading to diagnosis of pulmonary
      sequestration.

PMID- 22368545
TI  - Change of size and type of patent ductus arteriosus in a one year old infant
      during routine echocardiographic study.

PMID- 22368546
TI  - Transcatheter closure of symptomatic aortopulmonary window in an infant.
AB  - An aortopulmonary window is a rare congenital cardiac defect. In the majority of
      symptomatic neonates and infants, primary surgical repair is the treatment of
      choice. In selected infants, catheter closure of the defect with a device may be
      feasible. We report on the successful closure of an AP window in a 12 month old
      infant, using a 6mm Amplatzer septal occluder. The procedure and follow-up were
      uneventful.

PMID- 22368547
TI  - Central venous catheters in children and neonates (Part 3) - Access via the
      femoral vein.
AB  - BACKGROUND: Central venous access via the femoral vein (FV) is safe, relatively
      easy and very usual in infants and children undergoing cardiac surgery for
      congenital heart disease. It has a low insertion-related complication rate.
      RESULTS: It is therefore a good choice for short-term central venous lines and a
      preferred insertion site for less experienced staff. The maintenance-related
      complications of thrombus formation and infections are higher compared to the
      internal jugular and the subclavian venous access. CONCLUSIONS: Some of these
      complications are reduced by the use of heparin bonded catheters, routine use of
      antibiotics, and timely removal of these lines in patients with persistent signs
      of infection but without another focus being defined.

PMID- 22368548
TI  - Tachyarrhythmia: Presenting symptom of cardiac tumour.
AB  - BACKGROUND: Cardiac arrhythmia in an apparently healthy heart needs a detailed
      anatomical investigation to detect any unsuspected anomalies such as
      cardiomyopathy and cardiac tumours. RESULTS: We report cardiac tumours as a cause
      of tachyarrhythmias. CONCLUSION: Cardiac tumours are rare in childhood and should
      be considered as part of the differential diagnosis in a child presenting with
      cardiac signs and symptoms and treatment should be individualised for each
      patient.

PMID- 22368549
TI  - Scimitar syndrome in infancy.

PMID- 22368550
TI  - Balloon assisted technique for closure of large atrial septal defects.
AB  - Amplatzer device closure of large atrial septal defects is challenging. A large
      device tends to malalign with the plane of the interatrial septum or prolapses
      through the defect. We describe a balloon assisted technique which has been
      successfully used in over 300 cases without a single technical failure.

PMID- 22368551
TI  - Unusual case of ruptured sinus of Valsalva: rupture into left ventricle cavity
      along with distortion of mitral valve requiring double valve replacement.
AB  - We report a rare case of sinus of Valsalva aneurysm of left aortic sinus, which
      was bulging into left atrium (LA) distorting mitral valve and rupture into the
      left ventricle with severe aortic regurgitation in a 25 years old male patient.
      Due to the rupture, both aortic and mitral valves were irreparable and required a
      double valve replacement along with the closure of the neck of the aneurysmal
      cavity occupying the left atrial roof.

PMID- 22368552
TI  - The chest x-ray in congenital heart disease 1. Total anomalous pulmonary venous
      drainage and coarctation of the aorta.

PMID- 22368553
TI  - Asymptomatic cardiac rhabdomyoma in neonates: is surgery indicated?
AB  - BACKGROUND: Neonatal Tuberose sclerosis complex may be associated with
      symptomatic cardiac rhabdomyomas. Cardiac rhabdomyomas are the most common
      cardiac tumours. The symptoms include haemodynamic instability and life
      threatening arrhythmias usually requiring early surgical intervention. RESULTS:
      We report a case of a 32 week gestation newborn diagnosed with a right
      ventricular outflow tract mass and subsequently diagnosed with tuberose sclerosis
      that needed early surgical intervention. CONCLUSION: While this case needed early
      intervention, the need for surgical intervention in otherwise asymptomatic cases
      is debatable as neonatal cardiac rhabdomyomas can spontaneously regress.

PMID- 22368554
TI  - Coronary artery grafting in infants.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with cardiac vale repair is an
      uncommon surgery in infants. CABG is technically demanding in infants due to the
      small size not only of the coronary arteries but also the potential graft
      arteries. The short and long-term outcome of surgery is not known and thus has
      largely been avoided. RESULTS: We report the case histories of two infants in
      whom CABG was undertaken successfully as a life-saving measure. Case 1: This
      infant needed an arterial switch operation after which the right coronary artery
      (RCA) was stenosed resulting in low cardiac output. After the right internal
      mammary artery (RIMA) was used to anastamose the RCA, the hemodynamic status
      improved drastically. Case 2: This infant underwent surgical correction for
      Anomalous Left Coronary Artery from Pulmonary Artery (ALCAPA). Postoperatively,
      she was in low cardiac output. She was found to have an occluded left coronary
      artery and mitral regurgitation (MR). After she underwent left internal mammary
      artery (LIMA) to Left Anterior Descending (LAD) anastamosis and mitral valve
      repair, the clinical condition improved dramatically. CONCLUSION: CABG is an
      uncommon operation in infants. This surgery is technically difficult. The long
      term results are not known and there are very few reports for the same. Though
      such an operation is best avoided, it can be used as a desperate life saving
      measure.

PMID- 22368555
TI  - Organized intra-atrial thrombus in growing premature infant.
AB  - We report interesting echocardiographic images of the atrial septum in two
      growing premature infants related to the previous use of umbilical venous lines
      in the neonatal period. Complications related to central venous lines are well
      documented but when they are identified in follow up after several months, their
      relevance is difficult to establish. Atrial septal findings of organized clot in
      these asymptomatic infants needs to be correlated with details of neonatal care.

PMID- 22368556
TI  - Isolated subpulmonary membrane causing critical neonatal pulmonary stenosis with
      concordant atrioventricular and ventriculoarterial connections.
AB  - We report a rare case of isolated subpulmonary membrane leading to critical
      pulmonary stenosis in an infant. This anomaly needs to be differentiated from
      valvar pulmonary stenosis as both anomalies require different modality of
      treatment (surgical/catheter).

PMID- 22368557
TI  - Biventricular noncompaction: A rare cause of fetal distress and tricuspid
      regurgitation.
AB  - Isolated noncompaction of the ventricular myocardium involving both ventricles is
      a rare entity. Here we report a rare case of biventricular noncompaction
      presenting with features of fetal distress and moderate tricuspid regurgitation.
      Noncompaction of both ventricles was diagnosed at birth.

PMID- 22368558
TI  - Fungal endocarditis in a premature infant complicated by a right atrial mycetoma
      and inferior vena cava thrombosis.
AB  - The incidence of fungal endocarditis in premature infants is on the rise,
      reported in the last decade secondary to use of central venous lines, the
      frequent use of broad spectrum antibiotics and neonatal surgical interventions.
      Central line related thrombosis is a significant risk factor for persistent
      fungemia and end organ complications including endocarditis. We present a fatal
      case of progressive thrombosis of the inferior vena cava and right atrial
      mycetoma in a premature infant with candidemia who underwent ileostomy for bowel
      perforation. Renal failure occurred secondary to inferior vena cava thrombosis
      and right atrial mycetoma, both of which had a potential for hemodynamic
      compromise and embolism.

PMID- 22368559
TI  - The chest x-ray in congenital heart disease 2.

PMID- 22368561
TI  - An unusual vascular ring: Origin of a ductus arteriosus from an aberrant right
      subclavian artery in a neonate with tetralogy of Fallot.

PMID- 22368560
TI  - Symptomatic giant left atrial aneurysm in a child: a rare entity.
AB  - Isolated left atrial aneurysms are rare entities in clinical practice. Usually
      the condition is diagnosed in the second to fourth decades of life. The presence
      of such lesions in the pediatric age group is scantily described. We present a 2
      year boy who presented with complaints of excessive irritability, respiratory
      distress and swelling of the feet. On examination, child was tachypnoeic with
      irregularly irregular rhythm. Echo showed a huge aneurysmal LA appendage with
      severe left ventricle dysfunction. The child underwent surgical resection for
      same. Findings were confirmed intraoperatively but he continued to have low
      cardiac output state after the surgery, with frequent arrhythmias and expired on
      day 7 of surgery. The case is reviewed and compared with the available English
      literature.

PMID- 22368562
TI  - Diagnosis of aortic origin of a pulmonary artery by echocardiography.
AB  - The aortic origin of right or left branch pulmonary artery is a rare cardiac
      anomaly in which the right pulmonary artery usually arises from the ascending
      aorta just above the aortic sinuses, whereas the main pulmonary artery and the
      other pulmonary branch arise in their normal position. We report a rare case of
      isolated origin of right pulmonary artery from the ascending aorta.

PMID- 22368563
TI  - Pneumopericardium due to long sheath during transcatheter closure of PFO.

PMID- 22368565
TI  - Corience: A website dedicated to congenital heart defects.

PMID- 22368564
TI  - The caveats in the diagnosis of anomalous origin of left coronary artery from
      pulmonary artery (ALCAPA).
AB  - Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) is an
      infrequent, well described, but important anomaly of the coronary origin. Early
      diagnosis and prompt surgical treatment of the disease can be life saving.
      However, there are several potential sources of error in the seemingly simple
      stereotype diagnostic pattern. We report a case of ALCAPA and allude to some of
      the caveats in the diagnosis of this entity.

PMID- 22368566
TI  - The chest x-ray in congenital heart disease 3.

PMID- 22368567
TI  - Patent ductus arteriosus device embolization.
AB  - Nonsurgical closure of patent ductus arteriosus (PDA) using a duct occluder
      placed percutaneously is currently the first line of therapy and the success rate
      is quite high. Several devices are currently available. An eight year child
      underwent device closure of the ductus. However after deployment of the device
      it, became dislodged into the left pulmonary artery. Several attempts at catheter
      retrieval failed. The child underwent successful surgical removal of the device
      without cardiopulmonary bypass.

PMID- 22368568
TI  - Double orifice mitral valve associated with Ventricular Septal Defect in an
      infant: Case Report.
AB  - Double orifice mitral valve (DOMV) is an uncommon anomaly characterized by a
      mitral valve with a single fibrous annulus with two orifices opening into the
      left ventricle. Here we present a rare case of DOMV with ventricular septal
      defect (VSD) which was detected by 2-D echocardiography.

PMID- 22368569
TI  - Use of interventional catheterization before surgery in an adult with
      univentricular heart.

PMID- 22368570
TI  - Metastatic Ewing's Sarcoma to the Right Ventricle.

PMID- 22368571
TI  - Three-dimensional trans-esophageal Echocardiographic Evaluation of Atrial Septal
      Defects: A Pictorial Essay.
AB  - This pictorial assay illustrates the methodology of evaluating the atrial septal
      defects by three dimensional transesophageal echocardiography with the help of
      representative images. The article starts by discussing the technical details of
      how to acquire and crop the dataset to reconstruct the transesophageal three
      dimensional echocardiographic images of the inter atrial septum. Next, the
      anatomical details of the normal inter atrial septum are illustrated, followed by
      representative examples of all the possible defects of inter atrial septum. All
      the images have been reproduced in a uniform pattern which is similar to the view
      of the inter atrial septum that is seen in the real life situation by the
      surgeon.

PMID- 22368572
TI  - The chest x-ray in congenital heart disease 4.

PMID- 22368573
TI  - The impact of information technology on medicine.

PMID- 22368574
TI  - Dilated cardiomyopathy in childhood.
AB  - Dilated Cardiomyopathy is an uncommon disease in children but morbidity and
      mortality in affected patients are high. This review discuses clinical
      presentation, diagnosis, medical management and prognosis of the condition, with
      an emphasis on recent advances that have influenced management of these children.

PMID- 22368575
TI  - Computational fluid dynamics in paediatric cardiac surgery.
AB  - Computational fluid dynamics techniques have been applied to study both the local
      and the global haemodynamics created by different surgical reconstructions,
      currently used to treat complex congenital heart defects. These operations are
      characterised by competition of flows which can lead to postoperative failure of
      the surgical treatment. Different techniques have been used in order to improve
      knowledge of the global haemodynamics in patients submitted to such operations,
      and to devise possible optimal hydraulic designs of the connections. The adopted
      approach has combined highly-detailed, three-dimensional models of the
      connections with simplified zero-dimensional, lumped-parameter network models of
      the overall circulation of the patient. Three-dimensional models of the
      connections have been developed by means of the finite element method. Local
      fluid dynamics features have been analysed and then 'incorporated' in
      mathematical models able to predict some clinically relevant postoperative
      haemodynamic data. Results emphasise the impact of local geometry on global
      haemodynamics.

PMID- 22368576
TI  - Antibiotic prophylaxis cards for bacterial endocarditis.
AB  - Infective endocarditis is a largely preventable cause of morbidity and mortality
      in individuals with congenital heart disease. Patient and physician awareness is
      crucial, and in this regard, antibiotic prophylaxis cards are very helpful. I
      present an antibiotic prophylaxis card which is based on recent recommendations
      by the American Heart Association. This card is currently in use in Malta for
      both paediatric and adult patients.

PMID- 22368577
TI  - Management of congenital tracheal stenosis: a multidisciplinary approach.
AB  - Congenital tracheal stenosis is a rare but underdiagnosed anomaly which can
      present as life-threatening respiratory insufficiency in neonates and infants.
      Initial control of the airway is mandatory. Surgical correction is the mainstay
      of therapy and is achieved with low mortality. The type and extent of repair
      depends largely on the length of stenosis. Cardiac anomalies are frequently
      associated and may be addressed at the time of tracheal surgery. Despite initial
      satisfactory results, post-operative morbidity due to persistent granulation
      tissue is substantial. It is through a multidisciplinary approach and close
      follow-up of the repaired airway that these demanding patients are best cared
      for. The long-term quality of life remains uncertain.

PMID- 22368578
TI  - Telemedicine kept simple.
AB  - Telemedicine ("medicine from a distance") is about bringing specialist knowledge
      to a patient from afar, by the use of communication technology. This article is
      based on personal experience in helping set up a simple, versatile, cheap and
      effective store-and-forward telemedicine system for the British Defence Medical
      Services. This system uses readily available still digital cameras to record
      clinical, radiographic and microscopic images, which are then sent by electronic
      mail to an organised network of specialists for secondary or tertiary opinion.
      The system is in use in various countries throughout the world, and has also
      proven to have civilian and humanitarian uses. The system is now being emulated
      in civilian practice in the United Kingdom, the United States, and in previously
      isolated hospitals in the Third World. I also describe the active role played by
      a telemedicine charity and by medical students on elective in the Third World in
      setting up telemedicine links using this system. Readers are invited to co
      operate in the setting up of a global outreach telemedicine programme, linking
      elective students, isolated Third World hospitals, and University Teaching
      Hospitals.

PMID- 22368579
TI  - Heart disease in infants of diabetic mothers.
AB  - Congenital anomalies occur more commonly in infants born to diabetic mothers, and
      cardiac defects predominate. Although respiratory problems are also frequently
      found in those infants, they need to be differentiated from cardiovascular
      problems that such patients may also have, which include cardiovascular
      maladaptation to extra-uterine life, congenital heart defects and hypertrophic
      septal cardiomyopathy. A high index of suspicion is required as the specific
      management may vary and digoxin, or inotropic agents which may be used in heart
      failure associated with structural heart defects are contraindicated if
      hypertrophic cardiomyopathy is present. This article reviews the epidemiology,
      pathophysiology, clinical presentation, prognosis and available diagnostic and
      therapeutic modalities. The need for antenatal fetal echocardiography in pregnant
      diabetic mothers is also reviewed, as well as the controversial role of maternal
      glycemic control in the prevention of these anomalies.

PMID- 22368580
TI  - Categorisation of ventricular septal defects: review of the perimembranous
      morphology.
AB  - The Association for European Paediatric Cardiology, the Society of Thoracic
      Surgeons, and the European Association for Cardiothoracic Surgery, have recently
      published detailed hierarchical listings for the description of ventricular
      septal defects. This review details the anatomic basis for the European codes,
      illustrating the phenotypic features of the various holes that can be described
      as perimembranous ventricular septal defects.

PMID- 22368581
TI  - Perioperative anticoagulation for children with prosthetic mechanical valves.
AB  - The insertion of a mechanical heart valve predisposes to thrombosis and embolism,
      and for this reason, individuals with mechanical valves who undergo
      dental/surgical procedures must take special precautions. In this article, we
      illustrate a protocol for anticoagulation during such procedures in individuals
      with mechanical valves.

PMID- 22368582
TI  - Images in Paediatric Cardiology - no longer an infant!

PMID- 22368584
TI  - Isolated right pulmonary artery discontinuity.
AB  - Unilateral "absence" of the pulmonary artery is an uncommon malformation
      frequently associated with congenital heart disease. In fact, the pulmonary
      artery is typically discontinuous from the main pulmonary artery, not absent. We
      report a case of right pulmonary artery discontinuity not associated with
      congenital heart disease and review the embryogenesis and treatment of this rare
      congenital cardiac anomaly.

PMID- 22368583
TI  - Ventricular septal defects: morphology of the doubly committed juxtaarterial and
      muscular variants.
AB  - In our previous review of the phenotypic features of ventricular septal defects,
      we concentrated on the perimembranous variant, showing how its distinguishing
      feature, as viewed from the right ventricle, was fibrous continuity in its
      postero-inferior rim between the leaflets of the aortic and tricuspid valves. In
      this second review, we focus on the morphology of those defects which have
      exclusively muscular rims when viewed from their right side, and the variant with
      the phenotypic feature of fibrous continuity between the leaflets of the two
      arterial valves. As with the defects described as being perimembranous, once they
      have been characterised, it is the position of the defect relative to the
      components of the morphologically right ventricle that is the primary determinant
      of the options and strategies for treatment. Therefore, clarification of the
      morphology is the key to establishing the related risks for each particular
      defect.

PMID- 22368585
TI  - Mitral valve prolapse and mitral insufficiency in two siblings with Gaucher's
      disease.
AB  - Gaucher's disease is an autosomal recessive storage disorder. We report two
      siblings with Gaucher's disease, both of which had mitral valve prolapse and
      mitral insufficiency. One of the siblings died of bacterial endocarditis and
      pneumonia, while the other continues under followup.

PMID- 22368586
TI  - Of networks, large and small.
AB  - Computer networks are constantly and radically changing the way in which the
      medical professions thinks and works. This article briefly explores some of these
      innovations.

PMID- 22368587
TI  - Spontaneous regression of huge cardiac rhabdomyoma in an infant.
AB  - Rhabdomyomas are the most common primary cardiac tumors in childhood, and are
      often associated with tuberous sclerosis. We report a huge rhabdomyoma in an
      asymptomatic four hour old infant who presented initially with a murmur due to
      moderate subaortic stenosis. Followup showed regression of the tumour. Although
      the indications for surgical resection of symptomatic tumors are well
      established, medical follow-up should be the prefered treatment.

PMID- 22368588
TI  - Publishing on the WWW. Part 1 - Static graphics.
AB  - An on-line journal's ability to publish graphics at no additional cost is a major
      advantage over conventional printed journals. This article outlines technical,
      copyright and other issues related to graphic publishing on the world-wide-web.

PMID- 22368589
TI  - Do multivitamin supplements reduce the risk for congenital heart defects?
      Evidence and gaps.
AB  - Progress in the primary prevention of heart defects has been slow. Some findings
      suggest that multivitamin supplementation might reduce the risk for some heart
      defects. This review of the literature shows that two studies, one of which is a
      randomized clinical trial, provide data supporting a possible protective effect
      of multivitamins for all heart defects combined (a 25 to 50% reduction). Three of
      five studies support a protective effect for outflow tract defects, whereas two
      studies do not.More studies are clearly needed to elucidate the relation between
      multivitamin use and occurrence of heart defects. Such studies must take into
      account intake from multiple sources (diet and supplements), as well as genetic
      background and potential confounders. From a practical perspective, all health
      care providers, including pediatric cardiologists, should ensure that women of
      childbearing age, regardless of whether they had a previous child with a heart
      defect, take a multivitamin containing 400 micrograms of folic acid, to reduce
      their risk of having a baby with a neural tube defect. Should such supplements
      eventually be proven to reduce the risk also for heart defects, this would be an
      important additional benefit of such supplement use.

PMID- 22368590
TI  - Parasitic disease affecting the heart in childhood.
AB  - Parasitic diseases may occasionally affect the cardiovascular system, albeit
      rarely in childhood. In this paper, I list the main features of tropical diseases
      which may affect the heart.

PMID- 22368591
TI  - Publishing on the WWW. Part 2 - Copyright and the WWW.
AB  - Copyright on the Internet is becoming an increasingly important issue, as the
      copying of material in its original digital form is extremely easy, and such
      copies can be made without any degradation of the copies whatsoever. But what
      exactly is copyright? In this article, I will discuss copyright and related
      issues as defined by United States law, since the Internet was an American
      concept and continues to be dominated by the United States. Other countries have
      similar laws with relatively minor variations.

PMID- 22368592
TI  - The persistently patent arterial duct in the premature infant.
AB  - The presence of a persistently patent arterial duct is common in premature
      neonates and may be associated with high morbidity. Early accurate diagnosis,
      assessment of the significance of the left to right shunt and prompt treatment
      are required to improve the outcome in this infant population.

PMID- 22368593
TI  - Is arrhythmogenic right ventricular cardiomyopathy a paediatric problem too?
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease
      that is often familial, characterized by arrhythmias of right ventricular origin,
      due to transmural fatty or fibrofatty replacement of atrophic myocardium. ARVC is
      usually diagnosed in the clinical setting between 20 and 40 years of age. The
      disease is seldom recognised in infancy or under the age of 10, probably because
      the clinical expression of the disease is normally postponed to youth and
      adulthood. This review focuses its attention to the pediatric age, defined as the
      period of life raging from birth to 18 years. During this span of life, ARVC is
      not so rare as previously supposed and can be identified by applying the same
      diagnostic criteria proposed for the adult. Ventricular arrhythmias range from
      isolated ventricular arrhythmias to sustained ventricular tachycardia and
      fibrillation. Children and adolescents with ARVC must be carefully evaluated and
      followed-up especially when a family positive history is present, taking into
      account the high probability during this life-period that asymptomatic affected
      patients become symptomatic or that arrhythmias worsen during follow-up. The
      recent identification of the first defective gene opens new avenues for the early
      identification of affected subjects even when asymptomatic.

PMID- 22368595
TI  - Paediatrics in the XX century.

PMID- 22368594
TI  - Publishing on the WWW. Part 3 - Scanning medical images for screen presentation.
AB  - The purpose of this article is to remove the myths and black art surrounding
      electronic imaging and prove beyond doubt that any mind competent in the workings
      of the human body is capable of producing good on-screen images from adequate
      equipment. Note that in this day and age of SI units imaging still uses inches to
      describe diagonal screen size and pixels per inch to describe resolution.

PMID- 22368596
TI  - Prenatal diagnosis of congenital anomalies.
AB  - Up till the early 1970s, prenatal diagnosis of congenital anomalies was primarily
      aimed at detecting chromosomal abnormalities by amniocentesis.1. Over the last
      two decades, prenatal diagnosis has greatly benefited from advances in ultrasound
      technology and in our ability to detect microscopic and submicroscopic chromosome
      abnormalities as well as single gene disorders, leading to substantive
      improvements in detection of such congenital anomalies.2 At present, invasive
      prenatal diagnosis continues to be the gold standard for pregnancies at increased
      risk for chromosomal anomaly or other genetic disease, with chorionic villus
      sampling being the procedure of choice for the first trimester,3 whereas mid
      trimester amniocentesis continues to be the most common form of invasive
      procedure for prenatal diagnosis.4 Still, invasive techniques are restricted to
      subgroups at risk for anomalies, for whom such time-consuming procedures are
      believed to be cost-effective, also accounting for procedure-related abortive
      risks. In the low-risk population prenatal diagnosis generally consists of
      screening procedures by means of ultrasound and maternal serum biochemistry.

PMID- 22368597
TI  - Clinical manifestations of Noonan syndrome.
AB  - Noonan syndrome is a common genetic disorder characterized by facial anomalies,
      congenital heart defect, short stature, webbed neck, chest deformities and
      undescended testes. The phenotypic expression of Noonan syndrome is extremely
      variable, with some affected subjects showing only minor features of the
      syndrome. Cardiac malformations are also heterogeneous. Pulmonary stenosis, with
      or without dysplastic pulmonary valve and hypertrophic cardiomyopathy, are the
      "classic" cardiac defects reported in Noonan syndrome. However, atrial septal
      defect, atrioventricular septal defect, left-sided obstructive lesions, tetralogy
      of Fallot and patent ductus arteriosus have also been described. Autosomal
      dominant inheritance has been documented in some families, although many cases
      appear to be sporadic. The diagnosis of Noonan syndrome is at present purely
      clinical, because a "diagnostic" test is not available. Indeed, although a gene
      for Noonan syndrome has been recently mapped by linkage analysis to chromosome
      12q, the gene or genes of the syndrome have not been yet cloned.

PMID- 22368598
TI  - Publishing on the WWW. Part 4 - Pubmed Central: a publishing paradigm shift.
AB  - This article discusses the environment leading to the founding of the Pubmed
      Central database, and its likely effects on publishing as we know it.

PMID- 22368599
TI  - Paediatric practice in the 21 century.

PMID- 22368600
TI  - Contralateral recurrence of atrial myxoma - case report and review of the
      literature.
AB  - Cardiac myxomas are the most frequent cardiac tumors, and they have the
      capability for recurrence years after resection, in the same or in different
      cardiac chambers. Hence, follow-up is important. Contralateral recurrences of
      myxoma are uncommon. We report a 7 year old boy who had a right atrial myxoma
      resected, and who had recurrent myxoma in the left atrium. The literature
      regarding such recurrence is reviewed.

PMID- 22368602
TI  - Publishing on the WWW. Part 5 - A brief history of the Internet and the World
      Wide Web.
AB  - This article focuses on the history of the Internet and the World Wide Web, the
      media that in recent years have created the concept of objects existing 'on-line'
      in a virtual computer environment. These objects naturally include on-line
      journals such as Images in Paediatric Cardiology.

PMID- 22368601
TI  - Sex ratio imbalance in transposition of the great arteries and possible
      agricultural environmental risk factors.
AB  - A significant bias in sex ratio has been documented for several congenital
      cardiac malformations. Transposition of the great arteries has been associated
      with a such a bias but no explanation has been proposed for this bias. We
      evaluated 95 isolated livebirths with transposition of the great arteries cases
      referred to the Sicilian Registry of Congenital Malformations from 1991 to 1998.
      We found a statistically significant male bias of 2.8 and this was significantly
      associated with both maternal and paternal occupational exposure to agricultural
      chemicals for male infants with transposition, but not for female infants. This
      study raises new questions about the possible role played by environmental
      chemicals in relationship to birth defects and to sex ratio imbalance.

PMID- 22368603
TI  - Ethical issues in paediatric practice - part I: general principles.
AB  - Clinical problems with ethical implications pose an ever increasing dilemma in
      everyday medical practice, and this is particularly the case with ethical issues
      involving children and those unable to take their own decisions. In this
      editorial we shall review some of the general principles that guide medical
      ethical problems.

PMID- 22368604
TI  - Takayasu's arteritis in children - a review.
AB  - Takayasu's arteritis is an inflammatory disease of unknown origin involving
      aorta, its primary branches and pulmonary artery. This article briefly reviews
      the pathology, clinical features and treatment of Takayasu's arteritis, focusing
      mainly on the disease in children.

PMID- 22368606
TI  - Publishing on the WWW. Part 6 - Simple graphic manipulation.
AB  - Modern graphic manipulation software is quick and simple to use, and allows
      medical quality graphics to be produced for online publication. This article
      demonstrates, step by step, how submitted images are processed by the journal in
      preparation for publication.

PMID- 22368605
TI  - Ventricular assist devices in pediatrics.
AB  - The implantation of a mechanical circulatory device for end-stage ventricular
      failure is a possible therapeutic approach in adult and pediatric cardiac surgery
      and cardiology. The aim of this article is to present mechanical circulatory
      assist devices used in infants and children with special emphasis on
      extracorporeal membrane oxygenation, Berlin Heart assist device, centrifugal pump
      and Medos assist device. The success of long-term support with implantable
      ventricular assist devices in adults and children has led to their increasing use
      as a bridge to transplantation in patients with otherwise non-treatable left
      ventricular failure, by transforming a terminal phase heart condition into a
      treatable cardiopathy. Such therapy allows rehabilitation of patients before
      elective cardiac transplantation (by removing contraindications to
      transplantation mainly represented by organ impairment) or acting as a bridge to
      recovery of the native left ventricular function (depending on underlying cardiac
      disease). Treatment may also involve permanent device implantation when cardiac
      transplantation is contraindicated. Indications for the implantation of assisted
      circulation include all states of cardiac failure that are reversible within a
      variable period of time or that require heart transplantation. This article will
      address the current status of ventricular assist devices by examining historical
      aspects of its development, current technical issues and clinical features of
      pediatric ventricular assist devices, including indications and contraindications
      for support.

PMID- 22368607
TI  - The legitimacy and advantages of electronic publication.
AB  - This article discusses the diverse challenges that online publication has created
      for academic institutions, authors, journal editorial boards, publishers,
      libraries and readers.

PMID- 22368609
TI  - Ethical Issues in Paediatric Practice - Part II: Issues relating to disability.
AB  - Ethical issues in child care are often complicated by the child's inability to
      take responsibility in their own management decisions and, therefore, their
      reliance on third parties. This situation is further complicated in those
      children who have an underlying disability which may influence judgement
      decisions of the child's surrogate guardians, both toward over or under
      treatment. This is particularly the case with regard to decisions relating to
      life support, ongoing and quality of life, appropriate use of limited healthcare
      resources, and medical research. This article will explore the ethical principles
      which help to guide the medical management of such difficult cases.

PMID- 22368611
TI  - The Portable Document Format - PDF.
AB  - This article demonstrates how documents prepared in hypertext or word processor
      format can be saved in portable document format (PDF). These files are self
      contained documents that that have the same appearance on screen and in print,
      regardless of what kind of computer or printer are used, and regardless of what
      software package was originally used to for their creation. PDF files are
      compressed documents, invariably smaller than the original files, hence allowing
      rapid dissemination and download.

PMID- 22368610
TI  - Diagnosis and management of pulmonary arteriovenous malformations.
AB  - Pulmonary arteriovenous malformation is a rare anomaly that presents in several
      different ways. It can present as an isolated finding, or more often in the
      context of hereditary haemorrhagic telangiectasia. It can also complicate
      palliative surgery such as the Glenn operation for complex congenital heart
      disease with single ventricle physiology. Its management includes transcatheter
      embolization, which is the preferred mode of therapy, surgery (including
      resection of the affected lobe, segment, or the fistula itself), or rarely,
      medical therapy. Complications of the disease itself and of various modes of
      treatment are relatively common, and patients require close surveillance for
      possible recurrence, or development of new fistulas. In cases related to the
      Glenn operation, redirection of hepatic venous flow or heart transplantation may
      cure the problem.

PMID- 22368608
TI  - Inhaled nitric oxide applications in paediatric practice.
AB  - The nitric oxide pathway plays a pivotal, yet diverse, role in human physiology,
      including modulation of vascular tone, neural transmission and inflammation.
      Inhaled nitric oxide is a selective pulmonary vasodilator that has emerged
      rapidly as an important therapeutic agent. It finds its best applications in
      paediatrics; the use of iNO in term neonates with hypoxaemic respiratory failure,
      in the assessment of pulmonary vascular reactivity and in the treatment of
      postoperative pulmonary hypertension in congenital heart disease is well
      recognised and accepted. This review details the delivery and monitoring aspects
      of inhaled nitric oxide, its potential toxic and side effects and its
      applications in several cardiopulmonary disorders in paediatrics.

PMID- 22368612
TI  - A review of mechanical ventilation strategies in children following the Fontan
      procedure.
AB  - This article briefly outlines the development of the Fontan operation, and
      details ventilation strategies after such surgery.

PMID- 22368613
TI  - Rheumatic Fever.
AB  - Rheumatic fever is an immunologically mediated inflammatory disease, that occurs
      as a delayed sequel to group A streptococcal throat infection, in genetically
      susceptible individuals. Chronic rheumatic heart disease remains an important
      public health problem in developing countries. Aetiopathogenesis and guidelines
      for the diagnosis, prevention and treatment of acute rheumatic fever are
      reviewed.

PMID- 22368614
TI  - Ethical Issues in Paediatric Practice - Part III: Issues relating to the dying
      process.
AB  - Despite the application of robust ethical principles, complex issues in child
      care commonly result in ethical dilemmas with no clear answers. This is
      especially so in those 'life and death' decisions relating to continuing curative
      therapy or opting for palliative care. As with many situations in paediatrics,
      these decisions are complicated by difficulties in establishing clear prognostic
      outcomes both in terms of disease progression and timescales, the child's
      reliance on third parties, and appropriate use of resources. Great efforts are
      required to ensure family members are fully informed of the evolving clinical
      situation relating to their child, and helping them to accept the inevitability
      of death. Whenever possible, they should be encouraged to plan for their child's
      death in a manner that is most appropriate for them as an individual family. This
      article will explore the ethical principles which offer guidance in these
      situations, and strives toward: i) establishing the acceptance of death by the
      child and family, ii) ensuring 'quality time' for both family and their dying
      child and, iii) safeguarding the child's right to die with dignity.

PMID- 22368615
TI  - New insights in genetics of congenital heart defects.

PMID- 22368616
TI  - Three-dimensional echocardiography of ventricular septal defects.
AB  - Three-dimensional echocardiography is increasingly available. We report our
      experience with 3D reconstructions of ventricular septal defects: Unique images
      of all different types of ventricular septal defects are reconstructed from left
      and right ventricular en-face views. The images are discussed according to
      pathological classifications. The images shown in this article include all
      landmarks used in pathological classifications of ventricular septal defects to
      distinguish the different types of the defects and their extension directions.
      The possibility of visualizing the whole circumference prevents the examiner from
      under- or overestimating the size of a defect and gives the interventionalist a
      useful tool for patient and device selection for interventional VSD closure.

PMID- 22368617
TI  - Spontaneous closure of a large secundum atrial septal defect.
AB  - Large and untreated secundum atrial septal defects are closed in childhood in
      order to prevent significant rates of morbidity and mortality. Small defects
      often close spontaneously. We present a girl with a large atrial septal defect
      that underwent spontaneous closure at just over three years of age. The defect
      was haemodynamically significant and larger than conventional expectations for
      spontaneous closure.

PMID- 22368618
TI  - PubMed Central, Images and Brief Images.

PMID- 22368619
TI  - Non congenital heart disease aspects of Down's syndrome.
AB  - Down's syndrome is the commonest chromosomal anomaly with an incidence of about
      1:700 live births, and is often associated with various congenital anomalies.
      Moreover an appreciable proportion of health problems (immunological,
      hematological, etc) are frequently associated with this condition, and for this
      reason affected individuals benefit greatly from multidisciplinary management.
      Recent research strongly suggests that Down's syndrome is a contiguous gene
      syndrome, and it is unlikely that a single Down's syndrome chromosomal region is
      responsible for the typical phenotypic features. This review presents the most
      important genetic and medical features.

PMID- 22368620
TI  - Noninvasive assessment of arterial function in children: clinical applications.
AB  - Non invasive methods to assess arterial function are widely used in adults. The
      development and progression of arterial vascular disease is a multifactorial
      process that can start early in life, thus even in a pediatric population. Risk
      factors for cardiovascular disease mediate their effects by altering the
      structure, properties and function of wall and endothelial components of the
      arterial blood vessels. The ability to detect and monitor sub-clinical damage,
      representing the cumulative and integrated influence of risk factors in impairing
      arterial wall integrity, holds potential to further refine cardiovascular risk
      stratification and enable early intervention to prevent or attenuate disease
      progression. Measurements that provide more direct information in relation to
      changes in arterial wall integrity clearly hold predictive and therapeutic
      potential. The aim of this current review will be to describe the non-invasive
      procedure used in children to investigate the mechanical properties of a great
      elastic artery, the common carotid, and the endothelial function of the brachial
      artery. The accuracy of recording noninvasively the blood pressure wave contour
      along the arterial tree has been improved by the technique of applanation
      tonometry. The results obtained with these methods in previous studies are
      described.

PMID- 22368621
TI  - Management of an absent pulse following arterial catheterization.
AB  - Arterial cannulation is a common procedure for diagnostic as well as
      interventional catheterisation. The incidence of arterial damage varies from
      around 1% to 45 % depending on the size of the patient, size of catheters used,
      repeat procedures, pre-existing vascular disease and whether the procedure was
      interventional as opposed to diagnostic (twelve times higher risk with
      intervention). The absence of a pulse following catheterisation can result from
      spasm, local thrombus formation, formation of a flap of endothelium, dissection
      or avulsion of the artery. In order to minimize the risks of arterial damage the
      following factors may help: a clean puncture, small French catheters, tapered
      well-fitting introducer sheaths, a short procedure time and administration of
      heparin (50 to 100 units/kg with further dose/s if the procedure lasts more than
      75 minutes).

PMID- 22368622
TI  - Brief Images: Cerebral arteriovenous malformation.

PMID- 22368623
TI  - Pharmacological closure of the patent ductus arteriosus.
AB  - Pharmacological closure by indomethacin is customary if symptoms of PDA are not
      controlled adequately with fluid restriction and diuretics. Its use, however,
      requires a comprehensive clinical assessment of all the vital perinatal factors
      and a vigilant monitoring of the sick infant. Prophylactic use of indomethacin is
      discouraged. The decision to use pharmacological versus surgical treatment or
      both should be individualized based on evidence-based research and clinician's
      own experience. Surgical ligation remains the primary mode of therapy in cases of
      pharmacological treatment failure or recurrence.

PMID- 22368624
TI  - Publishing on the WWW. Part 8 - Creating standalone animations from the DICOM
      format.
AB  - Cardiology images and animations are often available in DICOM format. This
      article will briefly describe the simplest and least expensive methods of
      converting DICOM images to small and manageable AVI format files.

PMID- 22368625
TI  - Defining the morphologic phenotypes of atrial septal defects and interatrial
      communications.
AB  - True atrial septal defects are limited to deficiencies totally within the
      confines of the oval fossa and its antero-inferior rim. Other communications
      between the two atriums, such as the superior or inferior sinus venosus defects,
      coronary sinus defect, and the ostium primum defect, are less frequently seen.
      They represent interatrial communications rather than septal defects, since the
      communication between the atrial chambers is outside the confines of the true
      atrial septum. The ostium primum defect, for example, has all the characteristics
      of an atrioventricular septal defect, existing only in the setting of a common
      atrioventricular junction. The unifying physiological feature of all these
      variants, whether their morphology is that of a defect within the area of the
      oval fossa, or an opening elsewhere within the atrium, is that mixing of the
      systemic and pulmonary blood occurs at atrial level. In this review, we emphasise
      the distinction between true atrial septal defects and defects which result in
      communications between the atriums, underlining the phenotypic characteristics,
      along with the notable morphological features that are of significance in current
      strategies for clinical management.

PMID- 22368626
TI  - Balloon expandable stents for coarctation of the aorta: review of current status
      and technical considerations.
AB  - Balloon expandable stents have been used to manage coarctation of the aorta in
      selected patients with very encouraging results. After the successful use of the
      Palmaz stents in these lesions newer stents as well as modifications of the
      Palmaz stents have been introduced to achieve optimal results in these patients.
      In this review, the older as well as the newer type stents used in coarctation
      are discussed. Technical considerations to achieve successful stent implantation
      and choice is outlined.

PMID- 22368627
TI  - Amplatzer ASO device closure of secundum atrial septal defects and patent foramen
      ovale.
AB  - Transcatheter closure of atrial septal defects and patent foramen ovale is now a
      well established therapeutic option. In this paper, we illustrate, step by step,
      the technique of Amplatzer ASO closure of these defects.

PMID- 22368629
TI  - A review of congenital heart block.
AB  - Congenital heart block is a rare disorder. It has an incidence of about 1 in
      22,000 live births. It may be associated with high mortality and morbidity. This
      should generate a high index of suspicion for early diagnosis and aggressive
      therapy when appropriate. The congenital heart block associated with neonatal
      lupus is considered a form of passively acquired autoimmune disease in which
      maternal autoantibodies to the intracellular ribonucleoproteins Ro (SS-A) and La
      (SS-B), cross the placenta and injure the previously normal fetal heart. Women
      with serum titers of anti-Ro antibody carry a 3% risk of having a child with
      neonatal lupus syndrome. Recurrence rates are about 18%. We believe that serial
      echocardiograms should be acquired so that early diagnosis is made and aggressive
      therapy administered, if signs of conduction system disease such as PR interval
      prolongation by Doppler are found, so as to optimize the outcome. Establishment
      of guidelines for therapy have been set empirically, should signs of congenital
      heart block develop. Those patients whose congenital heart block is associated
      with structural heart disease have a higher morbidity and mortality, which is
      determined more by the underlying structural congenital heart disease than it is
      by the need for a pacemaker per se.

PMID- 22368630
TI  - Late presentation and successful treatment of classical scimitar syndrome.
AB  - Scimitar syndrome is a form of partial anomalous pulmonary venous drainage that
      is dramatically visible on plain chest radiography (CXR). In these individuals
      the entire venous drainage from the right lung enters a single anomalous large
      vein that descends to the inferior vena cava. This descending vein is visible on
      CXR as a curvilinear density along the right heart border and resembles the
      curved Turkish sword that gives the condition its name. Scimitar syndrome forms
      part of the large spectrum of associated conditions known as venolobar syndrome.
      These include right lung hypoplasia or sequestered segments of right lung,
      congenital heart disease and various others. We report the case of a young woman
      who presented incidentally, with a murmur, at 16 years of age. Full investigation
      including angiography showed a large atrial septal defect with right heart
      dilation and scimitar syndrome. She underwent surgical correction with uneventful
      and complete correction by baffling of the scimitar vein from its entry into the
      inferior vena to the left atrium through the enlarged atrial septal defect.

PMID- 22368631
TI  - Publishing on the WWW. Part 9 - Video codecs and decompressors.
AB  - Digital video and audio produce very large and unwieldy files. Codecs are used to
      shrink files and them play back in reduced file size format. This article
      disusses the advantages, disadvantages and tradeoffs in using codes, and briefly
      reviews the most commonly used codecs.

PMID- 22368628
TI  - The use of anticoagulation in pediatric cardiac disease.
AB  - Palliation and repair of increasingly complex congenital heart defects as well as
      the emergence of novel contexts has led to multiple scenarios in which a real or
      potential risk of thromboembolism may exist. While various anticoagulation
      methodologies have been well defined for adults, there are few studies relating
      directly to pediatric patients. This article reviews a number of specific
      pediatric disease states, the representative pediatric literature, and, where
      appropriate, the corresponding adult literature. In so doing, the art and science
      of pediatric cardiac anticoagulation is defined with the hope to engender further
      thought regarding future directions of study and therapy.

PMID- 22368632
TI  - Papillary fibroelastoma of the left atrium in a 3-year-old boy.
AB  - A 3 year old boy presented with a cardiac murmur. Except for mildly impaired
      physical condition that was more likely due to asthmatic bronchitis, he was
      asymptomatic. Cardiac echocardiography disclosed a large tumor in the left atrium
      originating from the interatrial septum. The patient was immediately referred to
      surgery for excision of the tumor. Histological examination of the tumor showed a
      typical papillary fibroelastoma. The occurrence of a papillary fibroelastoma in a
      child is a rarity.

PMID- 22368633
TI  - Real-time three-dimensional ultrasound - a valuable new tool in preoperative
      assessment of complex congenital cardiac disease.
AB  - Evaluating complex cardiac defects in small children preoperatively requires
      multiple diagnostic procedures including echocardiography, and also invasive
      methods such as cardiac catheterisation, computer-tomography and magnetic
      resonance imaging. We assessed the complex anatomy of the atrioventricular valves
      in atrioventricular septal defect using bedside real-time three-dimensional
      echocardiography and comparing these results to the anatomic findings at the time
      of operative intervention.

PMID- 22368634
TI  - Delayed Amplatzer device closure of atrial septal defect for persistent cyanosis
      after surgical correction of severe pulmonary stenosis in early infancy.
AB  - We present two patients who had delayed transcatheter closure of secundum atrial
      septal defects for persistent cyanosis after surgical repair of severe pulmonary
      stenosis. The defects (two in one patient) were closed uneventfully and
      successfully with Amplatzer ASO devices, with significant improvement in oxygen
      saturation. The staged approach and the complementary role of surgery and
      intervention are discussed.

PMID- 22368635
TI  - Idiopathic arterial calcification of infancy - a case report.
AB  - Idiopathic arterial calcification of infancy is a rare condition characterized by
      extensive calcification and stenosis of large and medium sized arteries. A ten
      day old female baby developed sudden shortness of breath and was treated with
      oxygen and antibiotics. Antenatal echocardiography showed calcification of the
      aorta and pulmonary arteries. Autopsy examination revealed extensive
      calcification in the walls of major arteries and vessels of several organs. The
      baby was found to have a karyotype of 47 chromosomes.

PMID- 22368636
TI  - Diffuse pulmonary arteriovenous malformation - a case report.

PMID- 22368637
TI  - Interventional treatment methods in patients with Marfan Syndrome.
AB  - Marfan syndrome is an autosomal dominant heritable connective tissue disorder
      which involves primarily the skeletal, ocular and cardiovascular system. The
      incidence of MS is on average 1: 10000 with 25-30% of cases caused by sporadic
      mutations.The leading cause of premature death in these patients is progressive
      dilatation and subsequent dissection of the ascending thoracic aorta resulting in
      cardiac tamponade, and left ventricular failure due to aortic regurgitation. Life
      expectancy is primarily determined by the severity of cardiovascular involvement,
      and has improved substantially over the last 20 years due to the advances in
      surgical and medical management.The optimum management of Marfan patients
      includes a lifelong surveillance with particular emphasis placed on aortic
      behaviour. Preventive replacement of various portions of the aorta has been a
      major contribution for improved life expectancy in these patients. The different
      surgical and interventional treatment options currently available will be further
      outlined in this review.

PMID- 22368638
TI  - Amplatzer device closure of an inferior venosus atrial septal defect after
      surgical closure of a secundum atrial septal defect.
AB  - We present a patient who had transcatheter closure of a low atrial septal defect
      which was overlooked during surgical closure of a secundum atrial septal defect.
      The residual defect was detected during ablation for atrial flutter, and was
      closed successfully during the same procedure with an Amplatzer atrial septal
      occluder (ASO) device.

PMID- 22368639
TI  - Surgical treatment of aortic coarctation.
AB  - Coarctation of the aorta accounts for about 8% of all congenital heart diseases.
      Since the first successful case of surgical treatment in 1944 by Crafoord and
      Nylin1 in Sweden, several surgical techniques have been employed in the treatment
      of this anomaly. Here, we review by illustration the various surgical options in
      coarctation of the aorta with emphasis on our preferred technique - the extended
      resection and end-to-end anastomosis. Why the extended resection technique? Our
      experience - and that of other institutions - has shown that this is a better
      option in childhood as it is associated with a lesser degree of recoarctation and
      subsequent need for re-intervention.2.

PMID- 22368640
TI  - Use of stents for correction of pulmonary artery branch stenosis.
AB  - We present a patient with tetralogy of Fallot who developed bilateral branch
      pulmonary artery stenosis following surgical repair that was refractory to
      balloon dilatation. Simultaneous stenting of both pulmonary arteries produced a
      good result.

PMID- 22368641
TI  - An unusual case of aortic obstruction.

PMID- 22368642
TI  - Right ventricular myocardium in Fallot's tetralogy: a light microscopic,
      morphometric and ultrastructural study.
AB  - AIMS: To analyze peroperative biopsies of RV myocardium in Tetralogy of Fallot by
      light microscopy, morphometry and electron microscopy in order to determine the
      degree of hypertrophy and degenerative changes and to correlate these changes
      with clinical and haemodynamic parameters. MATERIALS AND METHODS: Right
      ventricular myocardium obtained peroperatively during surgical correction of
      Tetralogy of Fallot along with age-matched control samples were processed for
      routine light and electron microscopy using standard processing techniques. Mean
      cell diameter was analyzed using manual morphometric methods and ultrastructural
      study was carried out using a Philips transmission electron microscope. RESULTS:
      The most consistent features of hypertrophy were the mitochondrial changes and
      increased nuclear convolutions. Majority of the patients had hypertrophy with
      mild to moderate degenerative changes. Severe degeneration was associated with
      irreversibility and was related to the severity and chronicity of the disease.
      There was a significant correlation of the morphological changes with clinical
      and haemodynamic parameters. CONCLUSIONS: Peroperative histomorphometric and
      ultrastructural evaluation of the RV myocardium in Tetralogy of Fallot reflects
      the effect of haemodynamic stresses on the right ventricular muscle and
      correlates with clinical cardiac dysfunction. It may be a useful adjunct in
      determining the time for surgical intervention and in predicting clinical
      outcome.

PMID- 22368643
TI  - How to achieve balloon stability in aortic valvuloplasty using rapid ventricular
      pacing.
AB  - Balloon aortic valvuloplasty is now the treatment of choice for congenital aortic
      stenosis. Balloon stability may be difficult to achieve and this may result in a
      suboptimal result or even valve damage. We describe the technique of rapid
      ventricular pacing as a safe and effective option for achieving balloon stability
      during aortic valvuloplasty.

PMID- 22368644
TI  - Transvenous pacemaker in a child less than 6 kg.

PMID- 22368645
TI  - Head-up-tilt testing in children: new perspectives using beat-to-beat blood
      pressure monitoring.
AB  - The head-up-tilt-test in pediatric patients for the evaluation of syncope shows a
      sensitivity of 35-85% and often requires pharmacological stimulation in order to
      improve its diagnostic value. We used a new device for beat-to-beat blood
      pressure monitoring combined with impedance cardiography in a 12-year-old girl
      during tilt testing. A seven seconds asystolia was provoked. The haemodynamic
      parameters showed clearly the drop in heart rate as well as in cardiac output,
      and returned to normal values after tilting back the patient. With the help of
      this new monitoring device, the sensitivity and specificity of head-up-tilt
      testing can probably be improved.

PMID- 22368646
TI  - Stenting of the aortic arch as an emergency palliation of aortic dissection after
      cardiac surgery in an infant.

PMID- 22368647
TI  - Stent implantation for coarctation facilitated by the anterograde trans-septal
      approach.

PMID- 22368648
TI  - Cardiovascular involvement in Kawaski Disease.

PMID- 22368649
TI  - Poststenotic aneurysm in a child with native coarctation of the aortic arch.

PMID- 22368650
TI  - Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/Velo-Cardio-Facial
      syndrome).
AB  - Deletion 22q11.2 syndrome (Del22) (DiGeorge/Velo-Cardio-Facial syndrome) is
      characterized by congenital heart defect (CHD), palatal anomalies, facial
      dysmorphisms, neonatal hypocalcemia, immune deficit, speech and learning
      disabilities. CHD is present in 75% of patients with Del22. The most frequently
      seen cardiac malformations are "conotruncal" defects, including tetralogy of
      Fallot (TF), pulmonary atresia with ventricular septal defect (PA-VSD), truncus
      arteriosus (TA), interrupted aortic arch (IAA), and ventricular septal defect
      (VSD). The study of the specific "cardiac phenotype" in patients with Del22 shows
      that a particular cardiac anatomy can be identied in these subjects. In addition
      to CHD, various organ systems can be involved, so that a multidisciplinary
      approach is needed in the evaluation of patients with Del22.

PMID- 22368652
TI  - A complicated case of renal artery stenosis.
AB  - We present a boy with bilateral renal artery stenosis who presented with severe
      hypertension and haemorrhagic stroke. The diagnostic workup along with a
      complication of eventual surgical intervention are demonstrated.

PMID- 22368651
TI  - Late coronary complications after arterial switch operation for transposition of
      great arteries. Clinical and therapeutic implications.
AB  - The arterial switch operation is the procedure of choice for correction of
      transposition of the great arteries. Although offering excellent long term
      results, this procedure is burdened by the risk of acute and subacute coronary
      occlusion. No guide-lines exist for the management of acute or chronic ischemia
      in this setting. We briefly review the literature and present the results of our
      institution.

PMID- 22368653
TI  - Acute modified Blalock-Taussing shunt obstruction successfully treated with
      urokinase and heparin.
AB  - Acute modified Blalock-Tuassig shunt obstruction due to thrombosis may be life
      threatening. We report non-invasive relief of shunt obstruction with thrombolysis
      and heparinisation, a potentially life-saving intervention that is applicable in
      all settings, including outside tertiary paediatric cardiology centres.

PMID- 22368654
TI  - Management of tetralogy of fallot with pulmonary atresia.
AB  - Tetralogy of Fallot with Pulmonary Atresia is an extreme form of tetralogy
      characterized by absence of flow from the right ventricle to the pulmonary
      arteries. Pulmonary blood flow is derived from a variety of sources, including
      native pulmonary artery branches and aorto-pulmonary collaterals with significant
      variability from patient to patient. Management must therefore be individualized
      to each patient's anatomy and physiology. Cardiac catheterization plays a crucial
      diagnostic and therapeutic role in this group of patients. This article is a
      concise review of the spectrum of anatomic variability seen in this lesion with
      an emphasis on diagnostic and therapeutic catheterization . It also highlights
      our staged surgical approach to this lesion and provides data on long-term
      outcome after complete intracardiac repair.

PMID- 22368655
TI  - Palliative balloon dilation of native coarctation of the aorta in a preterm
      infant.
AB  - The role of balloon dilation for native coarctation in neonates is controversial,
      due to the relatively high recurrence rate. Balloon dilation may however provide
      adequate palliation in preterm infants, by relieving symptoms and allowing
      somatic growth until definitive surgical repair can be performed. We report
      successful balloon angioplasty, on 2 occasions, in a preterm neonate with
      coarctation of the aorta and associated left ventricular cardiomyopathy.

PMID- 22368656
TI  - Cardiac hemangioma of the right atrium in a neonate: fetal management and
      expedited surgical resection.
AB  - Cardiac hemangioma is a rare tumor with a reported incidence of 1-2%. We describe
      the case of a neonate with a right atrial mass that was diagnosed prenatally. The
      fetus developed a supraventricular tachycardia and was delivered by cesarean
      section in the 35(th) week of gestation. The infant underwent surgery after 24
      hours to remove the mass which was diagnosed as a cardiac capillary-cavernous
      hemangioma.

PMID- 22368657
TI  - Cardiac catheter assessment of congenital heart disease prior to total
      cavopulmonary connection.
AB  - This paper summarises the rationale behind cardiac catheter assessment prior to
      surgical completion of the Fontan circulation in hearts with univentricular
      pathology.

PMID- 22368658
TI  - Anomalous right pulmonary artery from the aorta.
AB  - Anomalous origin of the right pulmonary artery is a rare form of congenital heart
      disease. It usually presents in early infancy with heart failure and rapid
      development of pulmonary hypertension. There are about 131 cases reported in the
      literature and we report one such case.

PMID- 22368659
TI  - Double lumen aortic arch in association with tetralogy of fallot.

PMID- 22368660
TI  - Balloon atrial septostomy: history and technique.

PMID- 22368662
TI  - A brief history of cardiac pacing.
AB  - This article is the first of three articles that will deal with pacing. The
      history and background leading to pacemakers as we know them is briefly
      discussed.

PMID- 22368661
TI  - Normal adult coronary angiography.
AB  - Children with congenital heart disease will grow into adults who may also develop
      coronary artery disease. This article attempts to familiarise practitioners that
      usually deal with congenital heart disease with the conventional views that are
      obtained during adult coronary angiography.

PMID- 22368663
TI  - A large, single pulmonary arteriovenous fistula presenting hours after birth.

PMID- 22368664
TI  - Normal adult echocardiography - parasternal views.
AB  - Children with congenital heart disease will grow into adults who may also develop
      adult heart disease. This article attempts to familiarise practitioners that
      usually deal with congenital heart disease with the conventional views that are
      obtained during adult echocardiography.

PMID- 22368665
TI  - Severe dilated cardiomyopathy as an unusual finding in a young infant with
      mucolipidosis type 2.
AB  - A neonate presented with mucopolysaccharidosis-like phenotypic expression and
      typical signs of dysostosis multiplex but without urinary excretion of
      glycosaminoglycans. Investigations of lysosomal enzymes in cultured fibroblasts
      revealed a mucolipidosis type 2, known as I-cell disease. We describe the fatal
      course of the patient due to complications of an uncommon dilated cardiomyopathy
      in this rare disease and discuss the pathogenesis.

PMID- 22368666
TI  - Mycoplasma pneumonia - an unusual cause of acute myocarditis in childhood.
AB  - Mycoplasma pneumoniae is primarily a respiratory pathogen but may affect exhibit
      a diverse range of presentations from asymptomatic infection to life threatening
      conditions. Myocarditis of varying severity is an unusual complication. We report
      a 6 year old with mycoplasma myocarditis, a rare age for such a presentation, and
      who responded well to treatment with no sequelae. Serological testing for
      Mycoplasma pneumoniae should be part of the routine work-up for myocarditis.

PMID- 22368667
TI  - Normal adult echocardiography - apical views.
AB  - Children with congenital heart disease will grow into adults who may also develop
      adult heart disease. This article is reviews the adult two and four chamber
      echocardiographic views, and is a continuation of the our previous article which
      dealt with the parasternal views.

PMID- 22368668
TI  - Pulse oximetry screening for clinically unrecognized critical congenital heart
      disease in the newborns.
AB  - AIM: To determine the incidence of clinically unrecognized critical congenital
      heart disease (CCHD) in the newborns by using pulse oximetric screening. METHODS:
      Pulse oximetry was performed on clinically normal newborns at 24-48 hours of age.
      If screening oxygen saturation (SpO(2)) was below 95%, echocardiography was then
      performed. Data regarding true and false positives as well as negatives were
      collected and analyzed. RESULTS: Pulse-oximetric screening was performed on 1847
      clinically normal newborns. Low SpO2 (<95%) was found in three babies two of them
      had CCHD, including one with transposition of the great vessels, one with
      complete atrioventricular canal with moderate tricuspid regurgitation
      (sensitivity: 100%; specificity: 99.8%; positive predictive value: 100%; negative
      predictive value: 100%; accuracy: 99.8%). CONCLUSIONS: In addition to routine
      physical examination in the newborn infants pulse oximetry may improve the early
      diagnosis CCHD in the newborn. If oxygen saturation in clinically normal newborns
      is below 95% at 24-48 hours of age, referral to a cardiology unit is suggested.

PMID- 22368669
TI  - Flipper coil closure of patent ductus arteriosus.
AB  - Transcatheter closure of patent ductus arteriosus is now a well established
      therapeutic option. In this paper, we illustrate step by step the technique of
      Flipper coil closure of small (<3mm) ducts.

PMID- 22368670
TI  - The Amplatzer duct occluder for PDA closure: indications, technique of
      implantation and clinical outcome.
AB  - Following its introduction into clinical practice, the Amplatzer duct occluder
      (ADO) has achieved a definite place in the armamentarium of the interventional
      cardiologist for the closure of moderate to large sized PDAs. The device combines
      ease of use, including retrievability and repositioning when required, and a high
      occlusion rate (>99% complete occlusion of PDA within 6 months of implant, with
      the majority of occlusions occurring within 24 hours of implant). Possible
      complications, such as device embolization, protrusion of the retention disc of
      the device into the aorta producing aortic obstruction, or obstruction of a
      branch pulmonary artery by the device are also uncommon and can be avoided by
      choosing the appropriate sized device (with the pulmonary end of the device being
      2mm larger in diameter than the minimum measured ductal diameter), and paying
      scrupulous attention to technique of deployment. The device can be safely
      deployed in infants >3.5 kg, and can currently close PDAs of upto 11 to 12mm in
      minimum diameter. A brief description of the device, the technique of
      implantation, and the clinical results to date are provided.

PMID- 22368671
TI  - Surgical closure of patent ductus arteriosus in pre-term babies.
AB  - OBJECTIVES: To present by illustration the surgical options in neonatal PDA
      closure with emphasis on clip application. METHODS: Photo/video-documentation of
      surgical closure of PDA in a neonate by clip application coupled with free-hand
      drawings showing PDA closure by ligation and division. Review of 38 neonates
      undergoing surgical PDA closure in our institution between 1998 and 2006.
      RESULTS: Overall survival following surgery was 100%. There was one case of
      residual PDA and three postoperative complications - 2 cases of pneumothorax and
      one chylothorax. CONCLUSION: The outcome of surgical closure of PDA in neonates
      is very good with zero mortality in our series and only few postoperative
      complications.

PMID- 22368672
TI  - Modified Echocardiographic views for concordant atrio-ventricular connection with
      discordant ventriculo-arterial connection or double outlet right ventricle and
      sub-pulmonary ventricular septal defect.

PMID- 22368673
TI  - Haemolysis after Amplatzer device closure of ventricular septal defect.
AB  - Over the last few years, a vast variety of devices have been developed to close
      various septal defects through the transcatheter route. Haemolysis has been
      documented after Amplatzer device closure of patent ductus arteriousus, atrial
      septal defect, and ventricular septal defect. We report one patient with self
      limiting haemolysis after implantation of an Amplatzer perimembranous VSD device.

PMID- 22368674
TI  - Central venous catheters in children and neonates - what is important?
AB  - Central venous access is an essential part of perioperative management for
      infants and children undergoing cardiac surgery for congenital heart disease. In
      addition, a thorough knowledge of the techniues for cannulation and placement of
      venous lines from the various percutaneously accessible sites is an important
      aspect of cardiac catheterization in this patient population. In the first of a
      series of papers describing the various approaches to venous access, we describe
      percutaneous cannulation of the subclavian vein. The standard approach, as well
      as potential difficulties, and how to overcome them, are described, as also the
      complications associated with this approach.

PMID- 22368675
TI  - Mediastinal widening on chest radiography caused by combined aortic valve disease
      and primary large B-cell lymphoma.
AB  - Poststenotic aortic root dilatation in patients with aortic valvular stenosis may
      result in mediastinal widening on chest radiograph. Main differential diagnosis
      of mediastinal widening is a tumour. In fact, besides atypical chest pain or
      dyspnoea at exertion secondary to compression of intrathoracic structures in the
      latter, symptoms may be absent. We report a case of combined aortic valve disease
      and additional primary large B-cell lymphoma.

PMID- 22368676
TI  - Pacemaker endocarditis due to Haemophilus parainfluenza: case report and
      literature review.
AB  - We report a case of pacemaker infective endocarditis in a 14 month old girl,
      caused by Haemophilus parainfluenzae. There are no other cases in children
      reported in the literature. We discuss the issues surrounding the case and the
      evidence which influenced our management.

PMID- 22368677
TI  - Is evaluation of hepatitis a immunity required or not?
AB  - Hepatitis A virus (HAV) infection is one of the most common causes of acute
      hepatitis and it is a serious health problem worldwide. HAV infection is a
      vaccine preventable disease that can produce the lifelong immunity seen in many
      developed countries with the vaccination schedule administered to children;
      however this vaccine is not used in developing countries at the present time.
      Improvements in food and water hygiene have caused a displacement of hepatitis A
      infection from children to adults which has increased mortality rates. Therefore
      evaluation of HAV immunity levels can help health authorities develop polices for
      prophylaxis especially in developing countries.

PMID- 22368678
TI  - IL28B polymorphism, Explanation for Different Responses to Therapy in Hepatitis C
      Patients.

PMID- 22368679
TI  - Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With
      Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis.
AB  - CONTEXT: Hepatitis delta virus (HDV) leads to the most severe form of chronic
      viral hepatitis. OBJECTIVES: To determine the prevalence of HDV and create pooled
      estimations of possible risk factors, a systematic review was conducted to
      collect all epidemiological studies on HDV among chronic hepatitis B patients in
      Iran. DATA SOURCES: In this systematic review, databases such as PubMed, Embase,
      ISI, Google scholar, and Iranian databases (MagIran, Iranmedex, and SID) were
      searched. STUDY SELECTION: Studies that clearly stated information about the
      number of HBsAg positive patients infected with HDV were selected. DATA
      EXTRACTION: The name of the city, the author's name, year of study, HDV detection
      method, sample size, HBsAg positive frequency, mean age, total prevalence of HDV,
      and risk factors were extracted. RESULTS: The pooled HDV prevalence was 7.8% (95%
      CI: 5.89 - 9.71). In the survey-data analysis, HDV prevalence was 6.61%. HDV
      prevalence was 30.47% (95% CI: 9.76 to 51.19), 14.4% (95% CI: 7.72 to 21.07), and
      4.94% (95% CI: 3.73 to 6.15) in cirrhotic, chronic-hepatitis, and inactive
      carrier patients, respectively. Pooled ORs were calculated for several factors
      common to Iranian HBsAg-positive patients, including history of blood transfusion
      [OR: 1.1 (95% CI: 0.40 to 2.98)], intravenous drug abuse [OR: 1.6 (95% CI: 0.78
      to 3.21)], previous hemodialysis [OR: 1.72 (95% CI: 0.79 to 3.76)], and HBeAg
      positive status [OR: 1.26 (95% CI: 0.66 to 2.4)]. CONCLUSIONS: The prevalence of
      HDV is less common in Iran than in endemic regions such as Italy and Turkey;
      however, it is a severe form of hepatitis in HBsAg-positive patients. The most
      probable route of HDV transmission is hematologic, which suggests the importance
      of blood screening for HDV, especially in groups with numerous blood
      transfusions.

PMID- 22368680
TI  - Hematological Adverse events and Sustained Viral Response in Children Undergoing
      Therapy for Chronic Hepatitis C Infection.
AB  - BACKGROUND: Treatment of hepatitis C virus (HCV) infection with interferon (IFN)
      and ribavirin (RBV) is associated with adverse events, which may affect the
      patient's adherence to the treatment regimen and the treatment efficacy.
      OBJECTIVES: The aim of this study was to assess the sustained viral response
      (SVR) and interdependence between the haematological characteristics (leukocyte
      count, platelet count, and haemoglobin levels) in patients with chronic hepatitis
      C (CHC) infection during treatment with IFN and RBV. PATIENTS AND METHODS: We
      conducted a retrospective cohort study of 170 children with CHC infection who
      completed treatment with IFN-alpha and RBV. The children were divided into 2
      groups: the first group (group I, n = 119) underwent a 48-week course of
      treatment with recombinant IFN alpha-2b (Intron A) at a dosage of 3 MU 3 times a
      week subcutaneously and RBV at a dosage of 15 mg/kg per day orally, and the
      second group (group II, n = 51) was administered pegylated IFN (peg-IFN)-alpha-2b
      (PegIntron) at a dosage of 1.5 MUg/kg per week subcutaneously and RBV at a dosage
      of 15 mg/kg per day orally for 48 weeks. The dose of IFN was not adjusted but
      that of ribavirin was in 2 children from group II. Hematological growth factors
      and erythropoietin were not used. SVR was defined as undetectable serum HCV RNA
      24 weeks after the end of treatment (study week 72). Serum HCV RNA was determined
      by performing polymerase chain reaction, and the HCV genotypes and hematological
      parameters were evaluated. Serum HCV RNA levels were analysed by descriptive
      statistics. Means and standard deviations were calculated for values collected at
      the baseline, on the 12th and 48th weeks during treatment, and after 24 weeks of
      untreated follow-up (study week 72). RESULTS: Eighty-six (50%) of the 170
      patients who underwent treatment achieved SVR: 62 (51%) out of 119 children from
      group I and 24 (47%) out of 51 from group II. The mean serum hemoglobin levels
      and leukocyte and platelet counts at week 12 were significantly lower than the
      baseline values in both responders and non-responders from both the groups (P <
      0.05). In the responders in group I, the mean levels of serum hemoglobin after 24
      weeks of treatment and at the end of therapy were significantly lower than the
      mean levels at baseline. In the group treated with peg-IFN-alpha-2b and RBV
      (group II), the mean serum hemoglobin levels at week 12 was lower in the
      responders than in the non-responders (P < 0.05). The decrease in the hemoglobin
      levels was associated with viral response. In both the responders and non
      responders from both the groups, leukocyte counts decreased during treatment, and
      after 12 weeks, they were more significantly lower than the baseline value. The
      decrease was more marked in children treated with peg-IFN-alpha-2b + RBV (P <
      0.05). After 12 weeks of treatment, the platelet count was low in children from
      group II who had achieved SVR. CONCLUSIONS: A mild decrease in hemoglobin levels
      and leukocyte and platelet counts during treatment with IFN and RBV in children
      with CHC infection may be factors responsible for SVR induction.

PMID- 22368681
TI  - The Correlation of Il28B Genotype With Sustained Virologic Response In Romanian
      patients With Chronic Hepatitis C.
AB  - BACKGROUND: Multiple variables influencing the sustained virologic response (SVR)
      in chronic hepatitis C have been evaluated. One of them is genetic polymorphism
      near the IL28B gene. OBJECTIVES: The aim of this study was to evaluate the
      influence of IL28B genotypes on SVR rates in a group of patients with chronic
      hepatitis C from the western part of Romania. PATIENTS AND METHODS: A
      retrospective study was performed in 107 consecutive patients, previously treated
      with standard-of-care medication for chronic hepatitis C, identified from the
      databases of 2 centers. Patient demographics, viral load before treatment and at
      12, 24, and 72 weeks from the treatment start, and IL28B genotype were evaluated.
      RESULTS: Among the 107 patents in the study group, 54 patients had SVR (50.5%),
      and 62 (57.9%) showed a complete early virologic response (cEVR). The SVR rates
      according to IL28B genotype were as follows: 73.1% in patients with genotype C/C,
      40.9% in those with genotype C/T, and 57.1% in those with genotype T/T (i.e.,
      73.1% among patients with the C/C genotype vs. 43.7% among those with non-C/C
      genotypes; P = 0.0126). The cEVR rates were 80.8% in patients with the C/C
      genotype vs. 51.2% in those with non-C/C genotypes (P = 0.011). CONCLUSIONS: In
      our cohort of 107 Caucasian HCV patients, the SVR rate was 50.5% with standard-of
      care treatment. The SVR rate was directly related to the IL28B genotype: 73.1% in
      the C/C genotype vs. 43.7% in non-C/C genotypes (P = 0.0126).

PMID- 22368682
TI  - Effect and Predictive Elements for 52 Weeks' Telbivudine Treatment on Naive HBeAg
      positive Chronic Hepatitis B.
AB  - BACKGROUND: Antiviral treatment with nucleoside analogs has been used for chronic
      hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and
      suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis
      Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral
      suppression. However, its resistance rate is relatively high during long-term
      application, due to low genetic barriers to resistance. So, it is necessary to
      increase the effect and reduce resistance with effective management, according to
      baseline factors and early on-treatment responses. OBJECTIVES: To reveal possible
      predictive factors of the effect of telbivudine (LdT) treatment on naive HBeAg
      positive chronic hepatitis B (CHB) patients to optimize treatment. PATIENTS AND
      METHODS: A total 71 naive chronic hepatitis B (CHB) patients who met the
      inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd
      for at least 52 weeks. Multiple logistic regression analyses were done to
      investigate the predictive values of baseline factors and responses at Week 24.
      RESULTS: The reduction in hepatitis virus B (HBV) DNA level was 6.44 +/- 2.38 lg
      copies/mL at Week 52 compared with baseline. The complete virus response (CVR),
      biochemical response (BR), serological response (SR), and drug resistance (DR)
      were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression
      analysis, baseline alanine aminotransferase (ALT) levels significantly affected
      CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were
      independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423).
      The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with
      patients with ALT <= 120 Iu/mL were statistically significant. The differences in
      SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA
      <= 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR
      were differed significantly between patients with HBV DNA lower than 300
      copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P =
      0.000, P = 0.0016, and P = 0.000, respectively). CONCLUSIONS: There were more
      responders among naive HBeAg-positive chronic hepatitis B patients with lower HBV
      DNA levels (especially lower than 107 copies/mL) and higher ALT values
      (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for
      treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is
      observed.

PMID- 22368683
TI  - Intravenous Drug Users Can Achieve a High Sustained Virological Response Rate:
      experience From Croatian Reference Center for Viral Hepatitis.
AB  - BACKGROUND: Hepatitis C virus (HCV) is one of the major infectious disease agents
      among injecting drug users (IVDUs). However, most of the IVDUs are not still
      treated. OBJECTIVES: To examine the treatment course, adherence, tolerability and
      safety profiles and SVR rates in IVDUs compared to non-IVDUs. PATIENTS AND
      METHODS: Demographic and clinical data were collected from medical records of 345
      adult patients diagnosed with chronic hepatitis C (CHC) who were treated with a
      PEG-IFN-alpha and ribavirin in Croatian Reference Center for Viral Hepatitis in
      Zagreb between January 2003 and January 2010. Efficacy, safety and tolerability
      treatment profiles were analyzed in IVDUs vs. non-IVDUs. Positive predictors for
      treatment outcome were evaluated by univariate and multivariate logistic
      regression. RESULTS: A total of 106 (30.46%) IVDUs were identified. The IVDUs
      were mainly male (81.13% vs. 52.30%, P = 0.0001), young (mean +/- SD age: 32.46
      +/- 5.33 y vs. 46.12 +/- 11.48 y, P = 0.0001), had lower fibrosis and HAI score
      (measured by ISHAK) and shorter duration of infection (mean +/- SD: 8.98 +/- 5.87
      vs. 16.79 +/- 8.99 y, P = 0.0001) compared to non-IVDU group. In IVDUs, genotype
      1a (24.52%) and 3a (38.68%) were predominant. There were no differences in
      completion rate between the two studied groups. IVDUs achieved a significantly
      higher rate of overall SVR (70.75% vs. 51.04%, P < 0.0009) and in genotypes 1 and
      4 (65.08% vs. 48.73%, P = 0.0294) vs. non-IVDUs. Treatment discontinuation rates
      due to side-effects were not significantly different in IVDUs and non-IVDUs
      (2.83% vs. 7.11%, P = 0.1390). IVDU group had a higher rate of lost to follow-up
      (13.21% vs. 4.60%, P = 0.0071). There were no statistically significant
      differences in SVR rate between IVDUs with, or without substitution therapy
      (55.55% vs. 74.62%, P = 0.0866). Independent predictors of SVR were age < 40
      years and genotypes 2 and 3. Type of PEG-IFN-alpha used was not associated with
      SVR. CONCLUSIONS: Treatment of CHC in IVDUs should strongly be encouraged as they
      have positive predictors for achieving SVR such as younger age, shorter duration
      of infection, and consequently favorable histological stage of the disease, and
      good adherence to treatment. There is no difference in safety and tolerability
      profiles of treatment in IVDUs compared to patients with no history of drug
      abuse.

PMID- 22368685
TI  - Seroepidemiology of hepatitis a in the croatian population.
AB  - BACKGROUND: Hepatitis A virus (HAV) has a worldwide distribution, although this
      distribution tends to be uneven among geographical regions and population groups.
      The prevalence of anti-HAV antibodies in the general population varies widely
      among countries. In Europe, the seroprevalence of HAV is reported to range from
      32% to 88%. OBJECTIVES: The aim of this study was to determine the seroprevalence
      of HAV among the general Croatian population. MATERIALS AND METHODS: During a 2
      year period (2008-2009), a total of 791 serum samples were tested for the
      presence of anti-HAV total (IgM+IgG) and anti-HAV IgM antibodies using an
      automated enzyme-linked fluorescent assay (Mini Vidas; bioMerieux, Marcy
      l'Etoile, France). RESULTS: The overall anti-HAV seroprevalence was 41.6%. The
      observed difference in the seroprevalence rates among male and female patients
      was not statistically significant (44% vs. 39.6%, P = 0.218). A marked increase
      in anti-HAV seropositivity with age was observed (P < 0.001). The seroprevalence
      did not differ significantly between participants residing in rural regions
      (45.3%) and those residing in urban regions (40.6%, P = 0.292). CONCLUSIONS: Our
      results corroborate those of seroprevalence studies in other developed countries.
      More than half of the Croatian population (59.4%) is susceptible to HAV
      infection. Older age is an important predictor for being anti-HAV positive.

PMID- 22368684
TI  - Frequency of HIV and HCV Co-Infections in Chronic HBV Patients Referred to
      Taleghani Hospital, Tehran, Iran from 2006 to 2010.
AB  - BACKGROUND: Co-infection with hepatitis C virus (HCV) and/or human
      immunodeficiency virus (HIV) in patients with chronic hepatitis B virus (HBV)
      infection can alter the course of the disease. OBJECTIVES: In this study, we
      investigated the frequency of HIV and/or HCV co-infection in chronic HBV patients
      and related risk factors in acquiring the HCV and or HIV co-infectionit. PATIENTS
      AND METHODS: We studied 264 chronic HBV patients who visited the Gastrointestinal
      and Liver Ward of the Taleghani Hospital, Tehran, Iran between 2006 and 2010.
      Demographic information and records of possible risky behavior were obtained.
      Antibodies against HBV, HCV, and HIV, levels of alanine transaminase (ALT) and
      aspartate transaminase (AST), and conversion from hepatitis B e antigen (HBeAg)
      to hepatitis B e antibody (HBeAb) were evaluated. RESULTS: Of 264 patients with
      chronic HBV in this study, 184 patients (70%) were men and 78 patients (30%) were
      women. Only 1 patient (0.37%) was positive for anti-HIV antibody, whereas 12
      patients (4.54%) were positive for anti-HCV antibody. None of the patients had co
      infection with all 3 viruses (HBV, HIV, and HCV). CONCLUSIONS: This study
      demonstrated that the prevalence of HCV is higher than that of HIV in chronic HBV
      patients. Since HCV or HIV co-infection affects the therapeutic outcome in
      chronic HBV patients, testing for HIV and HCV is recommended, especially for
      patients with a history of risky behavior.

PMID- 22368686
TI  - What is the performance of the Aspartate Aminotransferase to platelets Ratio
      Index in patients With Chronic Liver Disease?

PMID- 22368687
TI  - An estimate of transfusion-transmitted infection prevalence in general
      populations.

PMID- 22368689
TI  - Surface-modified hyaluronic acid hydrogels to capture endothelial progenitor
      cells.
AB  - A major challenge to the effective treatment of injured cardiovascular tissues is
      the promotion of endothelialization of damaged tissues and implanted devices. For
      this reason, there is a need for new biomaterials that promote endothelialization
      to enhance vascular repair. The goal of this work was to develop antibody
      modified polysaccharide-based hydrogels that could selectively capture
      endothelial progenitor cells (EPCs). We showed that CD34 antibody immobilization
      on hyaluronic acid (HA) hydrogels provides a suitable surface to capture EPCs.
      The effect of CD34 antibody immobilization on EPC adhesion was found to be
      dependent on antibody concentration. The highest level of EPC attachment was
      found to be 52.2 cells per mm(2) on 1% HA gels modified with 25 MUg mL(-1)
      antibody concentration. Macrophages did not exhibit significant attachment on
      these modified hydrogel surfaces compared to the EPCs, demonstrating the
      selectivity of the system. Hydrogels containing only HA, with or without
      immobilized CD34, did not allow for spreading of EPCs 48 h after cell seeding,
      even though the cells were adhered to the hydrogel surface. To promote spreading
      of EPCs, 2% (w/v) gelatin methacrylate (GelMA) containing HA hydrogels were
      synthesized and shown to improve cell spreading and elongation. This strategy
      could potentially be useful to enhance the biocompatibility of implants such as
      artificial heart valves or in other tissue engineering applications where
      formation of vascular structures is required.

PMID- 22368690
TI  - A case of idiopathic hypertrophic cranial pachymeningitis presenting high values
      of matrix metalloproteinase.
AB  - This report concerns a 53-year-old male patient with idiopathic hypertrophic
      cranial pachymeningitis who presented with multiple cranial nerve palsies (I, II,
      III, IV, V, VI). Brain magnetic resonance imaging showed diffuse thickening and
      gadolinium enhancement of the cerebral dura mater. A biopsy of the cerebral dura
      mater showed granulomatous vasculitis with histiocyte infiltration. Although both
      the serum rheumatoid factor (RF) and matrix metalloproteinase-3 (MMP-3) were
      high, the patient showed no signs of arthritis. He was anti-cyclic citrullinated
      peptide antibody negative, which makes the presence of comorbid chronic
      rheumatoid arthritis (RA) unlikely. The aetiology of the pachymeningitis was
      unknown, which led to the diagnosis of idiopathic hypertrophic cranial
      pachymeningitis. Steroid pulse therapy successfully diminished the patient's
      pachymeningitis and lowered both RF and MMP-3. High values of RF suggest the
      possible involvement of an autoimmune mechanism, and the MMP value may be an
      important indicator of the aetiology of pachymeningitis with granulomatous
      vasculitis.

PMID- 22368688
TI  - Drug Repurposing from an Academic Perspective.
AB  - Academia and small business research units are poised to play an increasing role
      in drug discovery, with drug repurposing as one of the major areas of activity.
      Here we summarize project status for a number of drugs or classes of drugs:
      raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R
      naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate
      and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi
      project experience we discuss strengths and weaknesses of academic-based drug
      repurposing research. Translational, target and disease foci are strategic
      advantages fostered by close proximity and frequent interactions between basic
      and clinical scientists, which often result in discovering new modes of action
      for approved drugs. On the other hand, lack of integration with pharmaceutical
      sciences and toxicology, lack of appropriate intellectual coverage and issues
      related to dosing and safety may lead to significant drawbacks. The development
      of a more streamlined regulatory process world-wide, and the development of pre
      competitive knowledge transfer systems such as a global healthcare database
      focused on regulatory and scientific information for drugs world-wide, are among
      the ideas proposed to improve the process of academic drug discovery and
      repurposing, and to overcome the "valley of death" by bridging basic to clinical
      sciences.

PMID- 22368691
TI  - Unusual recurrence of small cell lung carcinoma.
AB  - We report a case of malignant meningitis in a 63-year-old man with a background
      of treated small cell carcinoma. He presented with dizziness, vomiting and
      ataxia. His imaging investigations did not show any abnormalities, but lumbar
      puncture confirmed the diagnosis of malignant meningitis.

PMID- 22368693
TI  - Nuclear Division Index may Predict Neoplastic Colorectal Lesions.
AB  - BACKGROUND: Colorectal cancer (CRC) develops by accumulation of multiple genetic
      damages leading to genetic instability that can be evaluated by cytogenetic
      methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay
      (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in
      peripheral lymphocytes of patients with CRC and polyps versus patients with
      normal colonoscopy. METHODS: Blood samples were collected from patients after
      informed consent. By CBMN technique we assessed the proportion of mono-nucleated,
      bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate
      NDI. Data were statistically analyzed using the SPSS 11.0 package. RESULTS: 45
      patients were available for analysis, 23 men and 22 women, with a mean age of
      58.7+/-13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean
      NDI values were significantly smaller for patients with CRC or polyps than in
      patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference
      persisted for patients with neoplastic lesions (adenomas and carcinomas) when
      compared with patients with normal colonoscopy or non neoplastic (hyperplastic)
      polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of
      adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81%
      specificity of lower values (p=0.019). The NDI cut off value to predict the
      presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and
      a specificity of 82.8% (p=0.048). CONCLUSION: NDI may be useful in screening
      strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic
      biomarker.

PMID- 22368692
TI  - Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer
      Vaccines.
AB  - Lung cancer is the leading cause of all cancer deaths in the US. The
      international scientific and clinical community has made significant advances
      toward understanding specific molecular mechanisms underlying lung
      carcinogenesis; however, despite these insights and advances in surgery and
      chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains
      poor. Nonetheless, significant effort is being focused on advancing translational
      research evaluating the efficacy of novel targeted therapeutic strategies for
      lung cancer. Illustrative examples of this include antagonists of the epidermal
      growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as
      gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds
      targeting growth factors and/or their receptors that regulate tumor-associated
      angiogenic programs. In addition, with the increased awareness of the significant
      role chronically activated leukocytes play as potentiators of solid-tumor
      development, the role of innate and adaptive immune cells as regulators of lung
      carcinogenesis is being examined. While some of these studies are examining how
      novel therapeutic strategies may enhance the efficacy of lung cancer vaccines,
      others are evaluating the intrinsic characteristics of the immune response to
      lung cancer in order to identify rate-limiting molecular and/or cellular programs
      to target with novel anticancer therapeutics. In this article, we explore
      important aspects of the immune system and its role in regulating normal
      respiratory homeostasis compared with the immune response accompanying
      development of lung cancer. These hallmarks are then discussed in the context of
      recent efforts to develop lung cancer vaccines, where we have highlighted
      important concepts that must be taken into consideration for future development
      of novel therapeutic strategies and clinical trials assessing their efficacy.

PMID- 22368694
TI  - The importance of screening and prenatal diagnosis in the identification of the
      numerical chromosomal abnormalities.
AB  - BACKGROUND AND AIMS: The obstetric care of a pregnancy, as it is practiced today,
      includes non-invasive screening approaches as well as invasive procedures for the
      definitive prenatal diagnosis of fetal disorders correlations between indications
      for prenatal cytogenetic diagnosis and results of the chromosomal analysis made
      upon fetal cells. The aim of our study was to evaluate the correlations between
      the screening test results and results of chromosomal analysis on fetal cells.
      METHODS: Amniotic fluid samples from 1159 pregnant women were studied with the
      rapid FISH method and the cytogenetic analysis (karyotype). The results from both
      methods were compared. RESULTS: The indications to perform prenatal cytogenetic
      diagnosis for numerical chromosomal abnormalities were: abnormal results of
      double or triple test, advanced maternal age, fetal abnormality detected through
      ultrasound examination, and positive family history for chromosomal anomalies. In
      our study we identified 30 cases with abnormal numeric chromosomes (18 cases of
      trisomy 21, 4 cases of trisomy 18, 3 cases of trisomy X, 1 case of monosomy, 2
      cases of trisomy XYY, 1 case of trisomy XXY and 1 case of triploidy).
      CONCLUSIONS: This report confirms the importance of screening and the cytogenetic
      diagnosis in the identification of the numerical chromosomal abnormalities.

PMID- 22368695
TI  - A retrospective study of bacterial infections in cirrhosis.
AB  - AIM: To evaluate the incidence of bacterial infections (BI) in hepatic cirrhosis
      (HC), the pathogen agents involved, to define the risk factors and impact on
      prognosis. METHODS: There was a retrospective study that enrolled a total of 1046
      patients with HC admitted in our clinic between 1.10.2008-31.03.2009 (6 months).
      Clinical, biological and bacteriological data were monitored. RESULTS: 51
      patients (4.9%) were found with BI. In one patient BI was located in three sites:
      peritoneal, blood and urine, and in 7 patients BI was located in 2 sites. BI
      location was: peritoneal-26 cases, urinary-20 cases, pneumonia - 8 cases, skin -
      4 cases and bacteremia -1 case. 43 episodes were community acquired, while 17
      episodes were - nosocomial (peritoneal - 3 cases, lung - 6 cases, skin - 2 cases,
      urinary - 5 cases). Of the 26 cases with bacterial peritonitis, the etiologic
      agent was identified in three: E. coli, Klebsiella, Alcaligenes. 18% of patients
      with HC and BI presented upper GI bleeding. 12 cases required admission to the
      Intensive Care Unit, where the death rate reached 83%. The risk factors for BI in
      HC were: decompensated HC OR=58,23 (95% CI 8.63/1141.31), p-value 10-12, Child
      Pugh score C: OR =1.99 (95% CI 1.04/3.8), p-value= 0.02. CONCLUSIONS: In this
      study the rate of bacterial infections in HC is low compared with the literature
      (4.9% vs. 15-30%), because the study was retrospective, hence recorded only
      severe infections. We must actively seek infections in all hospitalized patients
      with HC, especially in the ones with decompensated cirrhosis and with upper GI
      bleeding.

PMID- 22368696
TI  - Particular Characteristics of Medical Rehabilitation in Patients Operated for
      Osteoarticular Tumors according to the Campanacci Method.
AB  - The modern treatment of the osteoarticular tumors requires a multidisciplinary
      approach. Due to their proximity to major neural and vascular pathways, to the
      fact that they affect young people, as well as because they can permanently
      impair the functionality of the limb, the preoperative assessment of the patients
      must be performed in detail (physical, imaging, biochemical and histological
      examination) in order to prepare for the surgical procedure with a minimum impact
      on the quality of the life of the patients. In the last 5 years, in the Clinic of
      Orthopedics of the Universitary Emergency Hospital of Bucharest 7 patients, aged
      between 25 and 40 years, with giant cell tumor were operated, the sex ratio being
      F/M : 5/2. The surgical procedures were radical, followed by adjuvant treatment
      and supportive therapy. The decision to follow a certain treatment must be taken
      with the full consent of the patient, taking into account the requirements of
      his/her daily life. The surgical intervention must have the full support of the
      teams of kinesitherapists, psychologists/psychiatrists and social worker. In
      these situations, the social integration was faster and the arthrodesis, as a
      therapeutic stage, was more easily accepted.

PMID- 22368697
TI  - Giant sarcomatoid carcinoma of the breast - a rare case report.
AB  - Metaplastic breast carcinoma breast is rare entity having mixture of epithelial
      and mesenchymal elements which contains overtly sarcoma-like elements on light
      microscopy and its clinical behaviour is not well documented. We are presenting a
      case in a 50 - year old female presented with a large swelling over the left side
      of the breast. On histopathology, diagnosis made as metaplastic carcinoma of the
      breast with sarcomatoid variant. The case merits presentation because of its
      rarity, low frequency of axillary metastasis and difficulty in interpreting the
      morphological features which correspond with prognosis.

PMID- 22368698
TI  - Spontaneous pneumothorax in a case of pulmonary langerhans cell histiocytosis.
AB  - Langerhans Cell Histiocytosis (LCH) is a rare disease involving clonal
      proliferation of Langerhans cells, abnormal cells deriving from bone marrow and
      capable of migrating from skin to lymph nodes. Clinically, its manifestations
      range from isolated bone lesions to multisystem disease. The authors present the
      case of 37 years old male, first diagnosed with Pulmonary LCH (PLCH) 9 years
      before current admission in thoracic surgery department, with left recurrent
      pneumothorax. The appropriate surgical resolution for this patient is
      thoracoscopic surgery with pleuro-pulmonary symphysis, resulting complete lung
      expansion. This procedure results in a significantly lower occurrence of
      subsequent same side pneumothorax, thus being the best choice for these patients.

PMID- 22368699
TI  - A case report of pseudo-subarachnoid hemorrhage.
AB  - BACKGROUND: The authors report an unusual case of the radiological appearance of
      diffuse subarachnoid hemorrhage on brain computed tomographic (CT) scan in a
      patient with post-resuscitation anoxic encephalopathy. CLINICAL PRESENTATION: A
      young man with chronic renal failure collapsed unconscious while starting
      hemodialysis and was revived after resuscitation for almost one hour. He was
      shifted to intensive care unit and subsequent CT scan after 3 days showed a
      picture compatible with diffuse subarachnoid hemorrhage. The subsequent lumbar
      puncture showed no evidence of subarchnoid hemorrhage while the attenuation at
      the basal cistern on CT brain was consistent with pseudosubarachnoid hemorrhage.
      A four vessel angiography done subsequently confirmed anoxic encephalopathy.
      CONCLUSION: Anoxic encephalopathy can mimic diffuse subarachnoid hemorrhage on
      CT.

PMID- 22368700
TI  - Hyperechogenic liver lesion.
AB  - Current paper focuses on an ultrasonography image representing a hyperechogenic
      liver lesion that appeared in less than a year time in a patient with clinical
      alarm signs. There are also described the steps for the final diagnosis, that
      proved to be geographical map steatosis and possible differential diagnoses
      together with brief literature correlations.

PMID- 22368701
TI  - Early repolarization syndrome- to be or not to be benign.
AB  - The early repolarization syndrome, particular electrocardiographic aspect defined
      as J point and concave ST segment elevation, interpreted by electrophysiologists
      as benign for over five decades, caused over the past three years many
      controversies. The trigger for controversy were the results of several, mostly
      retrospective, studies concluding that individuals with early repolarization
      syndrome in inferolateral leads are at higher risk of developing malignant
      ventricular arrhythmia and death of cardiovascular cause. Although there is more
      to be said and investigate about this phenomenon, it potential malignant nature
      can not be neglected. The purpose of this article is to present data regarding
      early repolarization epidemiology and pathogenesis, data resulting from the most
      important studies regarding arrhythmic risk and evaluation of individuals with
      early repolarization syndrome.

PMID- 22368702
TI  - New anticoagulants in the treatment of atrial fibrillation in 2011.

PMID- 22368704
TI  - The frequency and severity of medical malpractice claims: high risk and low risk
      specialties.

PMID- 22368703
TI  - Pulmonary manifestations of systemic autoimmune diseases.
AB  - Systemic autoimmune diseases (SAD) are a heterogeneous group of immunologically
      mediated inflammatory disorders including multiorgan involvement. As expected in
      a multisystem disease, the entire pulmonary system is vulnerable to injury. Any
      of its compartments may be independently or simultaneously affected. It is
      difficult to assess the true prevalence of lung disease in cases of SAD. In this
      article, we will review the pulmonary manifestations caused by systemic lupus
      erithematosus, rheumatoid arthritis, systemic sclerosis,
      polymyositis/dermatomyositis, Sjogren's syndrome, mixed connective tissue
      disease, Wegener's granulomatosis, Churg-Strauss syndrome, Goodpasture's
      syndrome, and ankylosing spondylitis.

PMID- 22368705
TI  - Highlights on dalfampridine - new therapy in all types of multiple sclerosis.

PMID- 22368706
TI  - Updates in surgical oncology.

PMID- 22368707
TI  - What's New in the Treatment of Melanoma.

PMID- 22368708
TI  - Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase
      2 (Cdk2) by platinum(II) phenanthroline complexes.
AB  - Inhibition of protein kinases in the fight against disease remains a constant
      challenge for medicinal chemists, who have screened multitudes of predominantly
      planar organic scaffolds, natural and synthetic, to identify potent-albeit not
      always selective-kinase inhibitors. Herein, in an effort to investigate the
      potential biological utility of metal-based compounds as inhibitors against the
      cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent
      kinase 2, we explore various parameters in planar platinum(II) complexes with
      substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to
      identify combinations that yield promising inhibitory activity. The individual
      ligands' steric requirements as well as their pattern of hydrogen bond
      donors/acceptors appear to alter inhibitory potency when modulated. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154
      011-0059-5) contains supplementary material, which is available to authorized
      users.

PMID- 22368709
TI  - Prescribing of potentially inappropriate medications for the elderly: an analysis
      based on the PRISCUS list.
AB  - BACKGROUND: The PRISCUS list of potentially inappropriate medications (PIM) for
      the elderly was published in 2010 and is the first systematically constructed
      list of this type in Germany. The aim of the present study is to estimate the
      baseline prevalence of the prescribing of PIM, as defined by the PRISCUS list.
      METHODS: Pseudonymized claims data from three statutory health insurances in
      Germany, which together covered more than 8 million insurants, for the year 2007
      were used to determine the age- and sex-standardized one-year period prevalence
      of PIM among the elderly, as well as the frequency of PIM prescribing per person.
      The study population included all insurants who were at least 65 years old and
      were continuously insured throughout the year 2007 or died during that year.
      RESULTS: Of the 804 400 elderly persons in the study population, 201 472 (25.0%)
      received at least one PIM prescription in 2007. The PIM prevalence was higher in
      women than in men (32.0% vs. 23.3%) and increased with age. The most commonly
      prescribed PIM were amitriptyline (2.6%), acetyldigoxin (2.4%), tetrazepam
      (2.0%), and oxazepam (2.0%). 8.8% of all elderly persons received the same PIM
      drug four or more times in 2007. CONCLUSION: These data show that PIM were
      frequently prescribed to elderly persons in Germany before the PRISCUS list was
      published. Medications on the PRISCUS list are not necessarily absolutely
      contraindicated, and this study contained no information about the individual
      risk/benefit analyses that may have been carried out before these drugs were
      prescribed; thus, no conclusion can be drawn about the prevalence of
      inappropriate prescribing. Further research is needed to validate the PRISCUS
      list, which was generated by expert consensus, as a basis for therapeutic
      guidelines in geriatric medicine.

PMID- 22368710
TI  - Correspondence (letter to the editor): S3 guideline was not mentioned.

PMID- 22368711
TI  - Correspondence (letter to the editor): Disappointing.

PMID- 22368714
TI  - Correspondence (letter to the editor): Body contouring surgery.

PMID- 22368715
TI  - Correspondence (letter to the editor): The reality of healthcare in Germany was
      partially ignored.

PMID- 22368716
TI  - Correspondence (letter to the editor): Doubts and questions remain.

PMID- 22368717
TI  - Correspondence (letter to the editor): Prevalence rises in postmenopausal women.

PMID- 22368718
TI  - Correspondence (letter to the editor): Authors' objectivity is in doubt.

PMID- 22368720
TI  - Correspondence (letter to the editor): Is this how times are changing?

PMID- 22368721
TI  - Functional bowel disorders in adults.
AB  - BACKGROUND: Chronic abdominal pain, bloating, constipation, diarrhea, and stool
      irregularity are common symptoms in primary care and gastroenterology. A routine
      diagnostic evaluation fails to reveal any underlying somatic condition in about
      half of the affected patients, who are therefore said to have a functional bowel
      disorder. Physicians are often unsure how extensive the work-up must be to
      exclude a somatic cause. METHODS: This review is based on a selective review of
      the literature, including published guidelines from Germany and abroad. RESULTS:
      Functional bowel disorders are diagnosed on the basis of a typical constellation
      of symptoms and the absence of pathological findings that would adequately
      explain them (exclusive criteria). The basic diagnostic assessment, consisting of
      a physical examination, basic laboratory tests, abdominal ultrasonography, and
      (in women) a gynecological examination, is supplemented by further testing that
      depends on the patient's symptoms. Colonoscopy is obligatory to rule out
      underlying pathological abnormalities. By communicating the diagnosis of
      irritable bowel syndrome to the patient, the physician shows that the patient's
      symptoms and concerns have been taken seriously. The mainstays of treatment are
      patient education on the benign course of the disease and the encouragement of a
      salubrious lifestyle. Further treatment options include dietary measures, time
      limited symptomatic treatment with drugs, and psychotherapy. CONCLUSION: The
      diagnosis of a functional bowel disorder is based on a thorough history (positive
      criteria) and a small battery of diagnostic tests to exclude somatic disease.
      Both the diagnostic assessment and the treatment should be carried out in
      accordance with published guidelines.

PMID- 22368722
TI  - A Theoretical Study of the Mechanism of the Desymmetrization of Cyclic meso
      Anhydrides by Chiral Amino Alcohols.
AB  - The alcoholysis of cyclic meso-anhydrides catalyzed by beta-amino alcohols has
      been investigated with DFT quantum mechanics to determine the mechanism of this
      reaction. Both nucleophilic catalysis and general base catalysis pathways are
      explored for methanol-induced ring opening of an anhydride catalyzed by a chiral
      amino alcohol. The nucleophilic pathway involves a late transition state with a
      high energy barrier. In this mechanism, methanolysis is expected to take place
      following the amine-induced ring opening of the anhydride. In the base-catalyzed
      mechanism, methanol attack on one carbonyl group of the meso-anhydride is
      assisted by the beta-amino alcohol; the amine functionality abstracts the
      methanol proton. The chiral amino alcohol also catalyzes the reaction by
      stabilizing the oxyanion that forms upon ring opening of the anhydride by
      hydrogen bonding with its alcoholic moiety. Both stepwise and concerted pathways
      have been studied for the general base catalysis route. Transition structures for
      both are found to be lower in energy than in the nucleophilic mechanism. Overall
      this study has shed light on the mechanism of the beta-amino alcohol-catalyzed
      alcoholysis of cyclic meso-anhydrides, showing that the nucleophilic pathway is
      approximately 100 kJ mol(-1) higher in energy than the general base pathway.

PMID- 22368723
TI  - Severe Spinal Cord Injury Causes Immediate Multi-cellular Dysfunction at the
      Chondro-Osseous Junction.
AB  - Spinal cord injury is associated with rapid bone loss and arrested long bone
      growth due to mechanisms that are poorly understood. In this study, we sought to
      determine the effects of severe T10 contusion spinal cord injury on the
      sublesional bone microenvironment in adolescent rats. A severe lower thoracic
      (vertebral T10) spinal cord injury was generated by weight drop (10 g*50 mm).
      Severely injured and body weight-matched uninjured male Sprague-Dawley rats were
      studied. At 3 and 5 days post-injury, we performed histological analysis of the
      distal femoral metaphysis, TUNEL assay, immunohistochemistry, real-time PCR, and
      western blot analysis compared to uninjured controls. We observed severe hindlimb
      functional deficits typical of this model. We detected uncoupled remodeling with
      increased osteoclast activity in the absence of osteoblast activity. We detected
      osteoblast, osteocyte, and chondrocyte apoptosis with suppressed osteoblast and
      chondrocyte proliferation and growth plate arrest due to spinal cord injury. We
      also detected altered gene expression in both whole bone extracts and bone marrow
      monocytes following spinal cord injury. We conclude that spinal cord injury
      results in altered gene expression of key regulators of osteoblast and
      chondrocyte activity. This leads to premature cellular apoptosis, suppressed
      cellular proliferation, growth plate arrest, and uncoupled bone remodeling in
      sublesional bone with unopposed osteoclastic resorption. 

PMID- 22368724
TI  - Dysmetabolic Signals in "Metabolically Healthy" Obesity.
AB  - BACKGROUND: Obesity is associated with decreased insulin sensitivity, atherogenic
      dyslipidemia and hypertension, but clinical studies have also identified a
      "metabolically healthy" obese phenotype.  OBJECTIVE: To compare the
      characteristics of so-called "metabolically healthy" obese (MHO), normal weight
      subjects (MHNW) and obese with insulin resistance in a nationally representative
      sample in the United States.  DESIGN, SETTING AND PARTICIPANTS: Insulin
      resistance was defined by a homeostatic model assessment (HOMA) value in the
      upper tertile for the entire NHANES cohort. "Metabolic health" was defined as the
      absence of diabetes, insulin resistance, metabolic syndrome, and lipid-lowering
      therapy. The study evaluated the 314 MHO, 1173 MHNW and 843 insulin-resistant
      obese from among the 6485 non-diabetic, nno-pregnant adults aged 20-79 years, who
      participated to the United States National Health and Nutrition Examination
      Survey, 1999-2004.  MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition and
      physical activity features.  RESULTS: MHO and MHNW groups were similar regarding
      age, and fasting glucose and triglyceride levels. MHO had higher insulin
      (P<0.0001), insulin resistance as measured with the homeostatic model (p<0.0001),
      non-HDL cholesterol (P=0.002 in females and P=0.049 in males) and C-reactive
      protein levels (P<0.0001 in females and P=0.038 in males), and lower high-density
      lipoprotein cholesterol (HDL) levels (P<0.002). In addition, MHO females had
      higher low-density lipoprotein (LDL) cholesterol levels (P=0.012) and systolic
      blood pressure (P=0.02), and lower intake of dietary fiber (P=0.0009) and levels
      of physical activity (p=0.002). Triglycerides levels were normal in the MHO
      group.  CONCLUSIONS: "Metabolically healthy" obese people have multiple
      dysmetabolic changes that may signal increased risk for coronary artery disease.

PMID- 22368725
TI  - Unraveling the Numerous Biosynthetic Products of the Marine Sediment-Derived
      Fungus, Aspergillus insulicola.
AB  - A new tripeptide, pre-sclerotiotide F (3), was isolated from a marine sediment
      derived fungus, Aspergillus insulicola, along with five known compounds, one of
      which was new at the time of isolation, scerotiotide F (4). The absolute
      configuration elucidation of the new compound was determined using a combination
      of NMR, HR-ESI-MS, and optical rotation analyses. Cytotoxicities were measured in
      vitro against selected cancer cells. The effects of pre-sclerotiotide F (3) and
      sclerotiotide F (4) on LPS-induced NF-kappaB and iNOS expression were also
      measured.

PMID- 22368726
TI  - Does Life Expectancy Affect Treatment of Women Aged 80 and Older with Early Stage
      Breast Cancers?
AB  - BACKGROUND: Data are needed on how life expectancy affects treatment decisions
      among women >=80 years with early stage breast cancer.  METHODS: We used the
      linked Surveillance Epidemiology and End Results-Medicare claims dataset from
      1992-2005 to identify women aged >=80 newly diagnosed with lymph node negative,
      estrogen receptor positive tumors, <=5 centimeters. To estimate life expectancy,
      we matched these women to women of similar age, region, and insurance, not
      diagnosed with breast cancer. We examined 5-year mortality of matched controls by
      illness burden (measured with the Charlson Comorbidity Index [CCI]) using Kaplan
      Meier statistics. We examined treatments received by estimated life expectancy
      within CCI levels. We further examined factors associated with receipt of
      radiotherapy after breast conserving surgery (BCS).  RESULTS: Of 9,932 women,
      39.6% underwent mastectomy, 30.4% received BCS plus radiotherapy, and 30.0%
      received BCS alone. Estimated 5-year mortality was 72% for women with CCIs of 3+,
      yet 38.0% of these women underwent mastectomy and 22.9% received radiotherapy
      after BCS. Conversely, estimated 5-year mortality was 36% for women with CCIs of
      0 and 26.6% received BCS alone. Age 80-84, urban residence, higher grade, recent
      diagnosis, mammography use, and low comorbidity, were factors associated with
      receiving radiotherapy after BCS. Among women with CCIs of 3+ treated with BCS,
      36.9% underwent radiotherapy.  CONCLUSIONS: Many women aged >=80 with limited
      life expectancies receive radiotherapy after BCS for treatment of early stage
      breast cancers while many in excellent health do not. More consideration needs to
      be given to patient life expectancy when considering breast cancer treatments.
      KEY WORDS: Breast cancer, older women, treatment, life expectancy, radiation.

PMID- 22368727
TI  - Higher Education and Health Investments: Does More Schooling Affect Preventive
      Health Care Use?
AB  - While it is well-known that individuals with higher levels of education consume
      more preventive medical care, there are several potential explanations for this
      stylized fact. These explanations include causal and non-causal mechanisms, and
      distinguishing among explanations is relevant for accessing the importance of
      educational spillovers on lifetime health outcomes as well as uncovering the
      determinants of preventive care. In this paper, we use regression analysis,
      sibling fixed effects, and matching estimators to examine the impact of education
      on preventive care. In particular, we use a cohort of 10,000 Wisconsin high
      school graduates that has been followed for nearly 50 years and find evidence
      that attending college is associated with an increase in the likelihood of using
      several types of preventive care by approximately five to fifteen percent for
      college attendees in the early 1960s. We also find that greater education may
      influence preventive care partly through occupational channels and access to
      care. These findings suggest that increases in education have the potential to
      spillover on long-term health choices.

PMID- 22368728
TI  - Preventing Diabetes and Atherosclerosis in Sub-Saharan Africa: Should the
      Metabolic Syndrome Have a Role?
AB  - Obesity, hypertension, atherosclerosis, and type 2 diabetes mellitus are
      increasing in all regions of sub-Saharan Africa. The metabolic syndrome is a
      valuable tool in predicting atherosclerosis and type 2 diabetes in populations in
      Europe and North America. However, the applicability of the metabolic syndrome to
      African populations has not been studied. Prior to investing scarce funds into
      diagnosing and treating the metabolic syndrome, primary research needs to be
      designed to determine the prevalence of the metabolic syndrome and its ability to
      detect early, treatable disease in Africa. Assessment of these data should make
      it possible to determine if it is more effective to focus on the metabolic
      syndrome as a whole or on obesity, hypertension, atherosclerosis, and type 2
      diabetes as individual conditions. This article is an overview of the
      presentation of metabolic syndrome variables in the Eastern, Western, and
      Southern regions of sub-Saharan Africa.

PMID- 22368729
TI  - Cholesterol, Inflammasomes, and Atherogenesis.
AB  - Plasma cholesterol levels have been strongly associated with atherogenesis,
      underscoring the role of lipid metabolism in defining cardiovascular disease
      risk. However, atherosclerotic plaque is highly dynamic and contains elements of
      both the innate and adaptive immune system that respond to the aberrant
      accumulation of lipids in the subendothelial space. Previous research has focused
      on defining how proinflammatory cytokines synthesized by macrophages, such as
      interleukin-1beta (IL-1beta), modulate the progression of atherosclerosis,
      supporting the notion that chronic inflammation accelerates atherogenesis. More
      recently, emphasis has been placed on the elucidation of the mechanisms that
      contribute to pro-IL-1beta production and finally its processing via multiprotein
      complexes termed the inflammasomes, a family of cytosolic multiprotein complexes
      that serve as sensors of either pathogen invasion or cellular stress (ie,
      cholesterol crystals) and work via triggering caspase-1-mediated processing of
      pro-IL-1beta to IL-1beta. Based on this link between cholesterol metabolism,
      NLRP3 inflammasome activation, and IL-1beta release, it is important to re
      evaluate how the atherogenic environment stimulates immune cells to produce IL
      1beta.

PMID- 22368730
TI  - Recent advances in the curative treatment of colorectal liver metastases.
AB  - Liver resection provides the basis for curative treatment of colorectal liver
      metastases (CLM), achieving 5-year survival rates as high as 58%. Use of this
      approach is limited by the number of patients whose CLM are resectable at the
      time of initial presentation and the risk of early recurrence after surgery,
      justifying development of modern perioperative chemotherapy regimens.
      Chemotherapy-associated hepatotoxicity led to development of standardized
      treatment strategies that balance the duration and timing of preoperative
      chemotherapy to minimize postoperative morbidity. The current challenge in the
      effort to offer curative treatment for CLM is selection of patients who will most
      benefit from an aggressive surgical approach. New end points of preoperative
      chemotherapy such as pathologic response and new radiologic response criteria
      have been evaluated as predictive factors for survival after liver resection and
      provide useful support in selecting patients for surgery.

PMID- 22368732
TI  - Hereditary gastrointestinal cancer syndromes.
AB  - The rapid growth of molecular genetics and its attendant germline mutation
      discoveries has enabled identification of persons who are at an inordinately high
      cancer risk and, therefore, ideal candidates for prevention. However, one must
      fully appreciate the extensive genotypic and phenotypic heterogeneity that exists
      in hereditary cancer. Once the causative germline mutation has been identified in
      a patient, high-risk members of the family can be similarly tested and identified
      and provided highly targeted surveillance and management opportunities. DNA
      testing can change the individual's presumed risk status and affect decision
      making by patients and their physicians regarding surveillance and management.
      Our purpose is to describe familial/hereditary cancers of the gastrointestinal
      tract, including familial Barrett's esophagus, hereditary diffuse gastric cancer,
      gastrointestinal stromal tumors, familial adenomatous polyposis and desmoid
      tumors, Lynch syndrome, small bowel cancer, and familial pancreatic cancer. We
      use our discussion of Lynch syndrome as a model for diagnostic and clinical
      translation strategies for all hereditary gastrointestinal tract cancers, which
      clearly can then be extended to cancer of all anatomic sites. Highly pertinent
      questions from the patient's perspective include the following: What kind of
      counseling will be provided to a patient with a Lynch syndrome mutation, and
      should that counseling be mandatory? Does the proband have the responsibility to
      inform relatives about the familial mutation, even if the relatives do not want
      to know whether they carry it? Is the patient is responsible for notifying family
      members that a parent or sibling has Lynch syndrome? Can notification be forced
      and, if so, under what circumstances? These questions point out the need for
      criteria regarding which family members to inform and how to inform them.

PMID- 22368733
TI  - Must Reading for GI Oncologists.

PMID- 22368734
TI  - Intraductal papillary mucinous adenocarcinoma of the pancreas: clinical outcomes,
      prognostic factors, and the role of adjuvant therapy.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) arising in intraductal
      papillary mucinous neoplasms (IPMN) may represent a different biologic entity
      than classic PDAC, and there is little evidence to inform adjuvant treatment
      decisions. The purpose of this study was to identify prognostic factors for PDAC
      arising in IPMN and determine the benefit of postoperative adjuvant therapy.
      METHODS: Forty-four patients without previous therapy who underwent surgery for
      invasive PDAC arising in association with IPMN at our institution were
      identified. Medical records were reviewed for clinical and pathologic features,
      adjuvant therapy, and outcomes. RESULTS: On univariate analysis, positive nodes
      (hazard rate [HR] 14, 95% confidence interval [CI] 4.2-44), CA 19-9 > 80 (HR 6.2,
      95% CI 2.2-17), lymphovascular invasion (HR 4.7, 95% CI 1.5-15), perineural
      invasion (HR 3.9, 95% CI 1.5-10), and positive margins (HR 3.1, 95% CI 1.2-8.0)
      were associated with inferior cancer-specific survival. Patients with positive
      nodes who received adjuvant therapy had higher median cancer-specific survival
      (20 months) than those who received no adjuvant therapy (3.3 months).
      CONCLUSIONS: Patients with PDAC arising in IPMN presented at an earlier stage
      than is reported for classical PDAC. Adjuvant chemoradiotherapy was associated
      with improved overall and cancer-specific survival for patients with advanced
      disease. These hypothesis-generating results require validation in a larger
      prospective trial.

PMID- 22368735
TI  - Advanced gastric cancer in jordan from 2004 to 2008: a study of epidemiology and
      outcomes.
AB  - BACKGROUND: WE REPORT THE EPIDEMIOLOGIC FEATURES AND THE TREATMENT EXPERIENCE OF
      ADVANCED GASTRIC CANCER (GC) AT KING HUSSEIN CANCER CENTER (KHCC) IN JORDAN, AND
      WE RETROSPECTIVELY COMPARE OUTCOMES OF TWO DIFFERENT REGIMENS: DCF
      (docetaxel/cisplatin/5-fluorouracil) vs. ECF (epirubicin/cisplatin/5
      fluorouracil). METHODS: Charts of 162 patients with inoperable GC treated between
      January 2004 and December 2008 were reviewed. A total 143 patients received
      chemotherapy (ECF = 113; DCF = 30). Choice of regimen was changed from ECF to DCF
      on January 2008 according to KHCC guidelines. RESULTS: The median patient age was
      59 years, with a male:female ratio of 1.8:1. Lymph nodes (67.9%) and liver
      (49.4%) were the most common sites of metastasis. Primary disease site was
      stomach in 78.4%, gastroesophageal junction in 16.7%, lower esophagus in 4.9%.
      Poorly differentiated histology was predominant (46.9%). Anemia (53.7%), pain
      (48.1%), and reflux (44.4%) were the most common presenting symptoms.
      Helicobacter pylori infection was present in 79%. Average time between initial
      symptom and diagnosis was 6.0 months. The overall response rate (ORR) was 59.3%
      with DCF and 32.6% with ECF (P = .01). Time to tumor progression (TTP) was 6.9
      months with DCF and 5.9 months with ECF (P = .005). Median survival was 11.0
      months with DCF and 10.2 months with ECF (P = .17). CONCLUSION: Some
      epidemiologic features of GC in Jordan mimic those of high-risk areas. Our
      outcomes of chemotherapy are comparable to internationally reported data and
      suggest superiority of DCF over ECF in terms of ORR and TTP.

PMID- 22368737
TI  - Small-cell carcinoma of the gallbladder: report of a case and literature review.

PMID- 22368736
TI  - Comparison of 1-, 2-, and 3-Dimensional Tumor Response Assessment After
      Neoadjuvant GTX-RT in Borderline-Resectable Pancreatic Cancer.
AB  - BACKGROUND: Facilitation of margin-negative resection is the goal of neoadjuvant
      therapy regimens used in the treatment of borderline-resectable pancreatic cancer
      patients. Multiple treatment approaches have shown efficacy in this setting,
      including neoadjuvant GTX (gemcitabine [Gemzar], docetaxel [Taxotere], and
      capecitabine [Xeloda]) and radiotherapy (RT). Three-dimensional tumor response
      may be a more accurate method of assessment compared to traditional 1- and 2
      dimensional techniques. We compared these 3 methods in a series of patients who
      underwent neoadjuvant GTX-RT and surgical resection. MATERIALS AND METHODS: This
      retrospective review included borderline-resectable pancreatic cancer patients
      treated with neoadjuvant GTX followed by 5-FU chemoradiotherapy with the intent
      of downstaging to resectability. Tumor was contoured on computed tomography (CT)
      scans obtained at the following time points: (A) initial staging, (B) CT
      simulation, and (C) restaging. These contours were used to determine tumor
      response according to WHO, RECIST, and volumetric criteria. RESULTS: Fourteen
      patients all experienced a measurable decrease in tumor volume following
      neoadjuvant therapy and were deemed suitable for at least surgical exploration.
      Radiotherapy was delivered to a median 50 Gy (range, 45-52 Gy) in 1.8-2.0 Gy
      fractions via 3-D conformal (21%) or IMRT (79%). The median percent volume
      changes before and after CT simulation were -3.4% and -52.6%, respectively. The
      overall median percent change was -54.5%. The corresponding absolute volume
      changes were -0.42 cm(3) (range, 9.12 to -12.47), -5.31 cm(3) (range, 2.06 to 
      15.93), and -6.72 cm(3) (range, 0.53 to -15.47), respectively. Response according
      to WHO, RECIST, and volumetric methods was identical with the exception of 1
      patient. CONCLUSION: This is the first study to quantify volumetric tumor change
      objectively as a result of neoadjuvant chemoradiotherapy for the treatment of
      borderline resectable pancreatic cancer. Our data suggest that tumor response to
      neoadjuvant therapy is essentially equivalent between 1-, 2-, and 3-dimensional
      assessment methods.

PMID- 22368738
TI  - Intratumoral Bleed in Small Bowel GIST Mimicking Peritonitis: An Unusual
      Presentation.

PMID- 22368739
TI  - Spontaneous regression of hepatocellular cancer: case report and review of
      literature.

PMID- 22368740
TI  - Brain metastasis and leptomeningeal carcinomatosis in a patient with
      cholangiocarcinoma.

PMID- 22368741
TI  - Waiting in line for cancer treatments?

PMID- 22368743
TI  - Attrition in Models of Intergenerational Links Using the PSID with Extensions to
      Health and to Sibling Models.
AB  - Selective attrition potentially biases estimation of intergenerational links in
      health and economic status. This paper documents attrition in the PSID through
      2007 for a cohort of children, and investigates attrition bias in
      intergenerational models predicting adult health, education and earnings,
      including models based on sibling differences. Although attrition affects
      unconditional means, the weighted PSID generally maintains its representativeness
      along key dimensions in comparison to the National Health Interview Survey. Using
      PSID, sibling correlations in outcomes and father-son correlations in earnings
      are not significantly affected by attrition. Models of intergenerational links
      with covariates yield more mixed results with females showing few robust impacts
      of attrition and males showing potential attrition bias for education and
      earnings outcomes. For adult health outcomes conditional on child background,
      neither gender shows significant impacts of attrition for the age ranges and
      models considered here. Sibling models do not produce robustly higher attrition
      impacts than individual models.

PMID- 22368744
TI  - [Intraperitoneal rupture of a hydatid cyst during pregnancy: report of a rare
      case].

PMID- 22368745
TI  - Trends in performance of the national measles case-based surveillance system,
      Ministry of Health and Child Welfare, Zimbabwe (1999 - 2008).
AB  - INTRODUCTION: Since adoption of the measles case-based surveillance system in
      Zimbabwe in 1998, data has been routinely collected at all levels of the health
      delivery system and sent to national level with little or no documented evidence
      of use to identify risky populations, monitor impact of interventions and measure
      progress towards achieving measles elimination. We analysed this data to
      determine trends in the national measles case-based surveillance system (NMCBSS).
      METHODS: A retrospective record review of the NMCBSS dataset for period 1999 
      2008 was conducted, assessing trends in proportions of investigated cases;
      timeliness and nature of specimens received at laboratory; timeliness of feedback
      of serology results, proportion of cases confirmed as measles and national
      annualized rates of investigation. Comparisons with WHO performance indicators
      were done. The secondary data analysis was done in Excel and Epi-Info statistical
      software. RESULTS: Cumulatively 4994 suspected cases were reported and
      investigated between 1999 and 2008. Reported suspected and confirmed measles
      cases declined from 24, 5% and 5.9% respectively in 2000 to 3.9% and 1.0%
      respectively in 2008. Proportion of cases with blood specimens collected and
      proportion reaching laboratory timely increased from 83% and 65% respectively in
      1999, to 100% and 82% respectively in 2008. Proportion of specimens arriving at
      laboratory in good condition improved from 65% in 2004 to 94% in 2008 while
      timeliness of feedback of serology results improved from 4% in 2004 to 65% in
      2008. Sensitivity of the NMCBSS however has been weakening, declining from 9.04
      cases investigated per 100,000 population per year in 2000 to 1.58
      cases/100,000/year in 2008. CONCLUSION: The NMCBSS improved in quality,
      timeliness and feedback of laboratory results of specimens sent for
      investigation, but its sensitivity declined mainly due to reduced capacity to
      detect and confirm measles cases. We recommend training staff on active
      surveillance of cases and more support and supervisory visits to strengthen EPI
      surveillance.

PMID- 22368746
TI  - [Microdeletion syndromes (Williams syndrome and deletion syndrome 22q11) at CHU
      Hassan II of Fez: report of 3 observations].

PMID- 22368747
TI  - [The Cri du Chat syndrome: report of an observation].

PMID- 22368748
TI  - [Response to El M'rabet FZ et al.: Splenic metastasis from colonic adenocarcinoma
      - about a case and literature review].

PMID- 22368749
TI  - Normotensive offspring of hypertensive Nigerians have increased left ventricular
      mass and abnormal geometric patterns.
AB  - BACKGROUND: Reports have shown that normotensive offspring of hypertensive
      parents (OHP) are at increased risk of developing systemic hypertension (SH) and
      adverse cardiovascular events later in life. The pathological antecedents of this
      are thought to be alterations in the structure and function of left ventricle.
      Therefore, the present study aimed at determining left ventricular mass and
      geometry in OHP and compared with offspring without parental hypertension.
      METHODS: Sixty-five OHP aged 15-25 years with 65-age and sex-matched offspring of
      normotensive parents (ONP) were studied for early makers of hypertensive
      cardiovascular disease. Those with heart murmurs, structural heart diseases and
      blood pressure >= 140/90 mmHg were excluded. Electrocardiography (ECG) and
      echocardiogram were done in standard positions. RESULTS: Mean left ventricular
      posterior wall thickness, left ventricular mass, left ventricular mass index
      (LVMI) and relative wall thickness (RWT) were significantly higher in the
      subjects than controls (p=0.001, 0.046, 0.03 and 0.004 respectively). LVMI
      correlated positively with systolic and diastolic blood pressure, waist
      circumference (WC), ECG voltage, and posterior wall diastolic dimension. Waist
      circumference was an independent predictor of LVMI in OHP. CONCLUSION: We
      concluded that normotensive OHP have alterations in left ventricular mass and
      structure; and should be considered as a special group that needs early dietary
      and lifestyle adjustments to prevent future cardiovascular events.

PMID- 22368750
TI  - [Postmenopausal tuberculous endometritis simulating endometrial cancer: report of
      a case].

PMID- 22368751
TI  - The National Cardiothoracic Centre, Accra Ghana: proceedings of the second
      International Update Course in Cardiology - improving the coverage of cardiology
      services.
AB  - Many developing countries now face the growing phenomenon of the double burden of
      disease. Most are still grappling with infectious diseases resulting from poor
      environmental sanitation and lack of access to good drinking water like malaria,
      cholera, and enteric fever. At the same time changes in diet and lifestyle in
      general in these countries is resulting in increasing numbers of people with
      obesity, sedentary life styles, increased salt intake from fast foods, increased
      smoking and consumption of alcohol and fizzy drinks, hypertension and diabetes.
      To increase the scope and depth of cardiovascular care in Ghana, the National
      Cardiothoracic Centre, (NCTC), organised the 2nd International Update Course in
      Cardiology for cardiologists and general practitioners, with emphasis on a
      practical approach to cardiology. Post conference evaluation indicated that the
      course was very useful especially for practitioners in district and regional
      hospitals. Close to 98% of the participants revealed that the update course will
      greatly impact positively on their management of cardiovascular diseases.

PMID- 22368752
TI  - [Pulmonary hypertension in scleroderma: about 12 cases].

PMID- 22368753
TI  - The epidemiological features of lymphoid malignancies in Benin City, Nigeria: a
      15 years study.
AB  - INTRODUCTION: Lymphoid malignancies compose a wide spectrum of different
      morphologic and clinical syndromes known to vary widely throughout the world. The
      purpose of this study is to determine the prevalence and time trends of lymphoid
      malignancies. METHODS: A 15 (May 1st 1996-April 30th 2010) years study of all
      patients who had lymph node biopsy at the Department of Haematology and
      Pathology, University of Benin Teaching Hospital, Benin City, Nigeria. RESULTS:
      The 391 patients had a male preponderance (M:F; 1.6:1). An increase in the
      lymphoid malignant cases was noted from 95 cases in the first 5-year interval
      (1996-2000) to 179 cases in the last 5-year interval (2006-2010) giving an
      average increase of 84.0%. Non-Hodgkins lymphoma (61.1%) and chronic lymphocytic
      leukaemia (18.2%) were the most frequent followed by Hodgkin's lymphoma and
      myeloma with equal proportions of 9.0% each. A positive correlation with a
      significant linear trends was obtained (r=0.1949, p<0.0001). Geographic areas at
      risk were found mainly in patients residing in Delta State (67.0%) which is a
      major oil producing state and Edo State (30.4%) where the hospital is located,
      both in the Niger Delta Region of Nigeria. CONCLUSION: Future research into
      environmental agents and genetic makeup/HLA typing of patients can be carried
      out.

PMID- 22368754
TI  - Physical activity and cardiovascular disease risk factors among young and middle
      aged men in urban Mwanza, Tanzania.
AB  - BACKGROUND: Cardiovascular diseases (CVD) risk factors are increasing at an
      unprecedented rate in developing countries. However, fewer studies have evaluated
      the role of physical activity in preventing CVD in these countries. We assessed
      level physical activity and its relationship with CVD risk factors among young
      and middle aged men in a fast growing city of Mwanza in Tanzania. METHODS:
      Physical activity was assessed among 97 healthy men aged 20-50 years using Sub
      Saharan Africa Activity Questionnaire. An updated compendium of physical activity
      was used to code the metabolic equivalent. Energy expenditure was calculated
      using Harris Benedict equation. Anthropometric measurements, blood pressure,
      fasting blood glucose and serum lipids were also measured. RESULTS: The mean
      energy expenditure in this population was 6,466 +/- 252 kcal/week. More than half
      (53.6%) of the participants had energy expenditure of >= 4,000 kcal/week. Only
      three (3.1%) had energy expenditure below the recommended 1,000 kcal/week. Except
      for hypertension, prevalence of CVD risk factors was low in this population;
      hypertension 23.7%, low HDL-cholesterol 10.3%, high LDL-cholesterol 9.3% and
      obesity 4.1%. Physical activity energy expenditure had an inversely relationship
      with waist to hip ratio, systolic blood pressure, heart rate, total cholesterol,
      HDL-cholesterol, LDL-cholesterol, triglycerides and fasting blood glucose.
      CONCLUSION: Physical activity energy expenditure was high in this population and
      was inversely correlated with CVD risk factors. Physical activity may play an
      important role in the prevention of CVD in this urban population of young and
      middle aged men.

PMID- 22368755
TI  - [Prevalence of orthostatic hypotension and its risk factors in treated
      hypertensive black Africans].

PMID- 22368756
TI  - Determining the prevalence of human immunodeficiency virus-associated nephropathy
      (HIVAN) using proteinuria and ultrasound findings in a Nigerian paediatric HIV
      population.
AB  - BACKGROUND: HIV associated nephropathy (HIVAN) is the most common form of chronic
      kidney disease resulting directly from HIV infection. The true prevalence of
      HIVAN in the paediatric population of West Africa is unknown, largely due to lack
      of surveillance and reporting of kidney disease in HIV positive patients.
      METHODS: This was a prospective study over a six month period( July to December
      2008) conducted in the Infectious Disease Unit of the Department of Paediatrics,
      University of Uyo Teaching Hospital, Uyo, Nigeria involving all confirmed cases
      of paediatric HIV infection. Urine microalbuminuria using calculated urine
      albumin - creatinine ratio was determined and repeated in 4 weeks interval. CD4
      count and renal ultrasonography was done for all the patients. The correlation of
      urine albumin - creatinine ratio with CD4 count, duration of treatment with
      highly active antiretroviral therapy (HAART) and association with clinical
      staging of the disease was also examined. RESULTS: Fifty - nine (60.2%) were
      males, thirty - nine (39.8%) were females with male to female ratio of 1.5:1. The
      prevalence rate of 31.6% HIVAN was found, out of which 3.1% had abnormal
      ultrasound findings. There was a significant correlation between CD4 count and
      urine albumin - creatinine ratio (r=-0.22, p=0.03). There was no correlation
      between urine albumin - creatinine ratio and duration on HAART (r=-0.10, p=0.31).
      CONCLUSION: Screening for microalbuminuria is essential for the early diagnosis
      and treatment of HIVAN in this age group.

PMID- 22368757
TI  - Purchasing power of civil servant health workers in Mozambique.
AB  - BACKGROUND: Health workers' purchasing power is an important consideration in the
      development of strategies for health workforce development. This work explores
      the purchasing power variation of Mozambican public sector health workers,
      between 1999 and 2007. In general, the calculated purchasing power increased for
      most careers under study, and the highest percentage increase was observed for
      the lowest remuneration careers, contributing in this way for a relative
      reduction in the difference between the higher and the lower salaries. METHODS:
      This was done through a simple and easy-to-apply methodology to estimate
      salaries' capitalization rate, by means of the accumulated inflation rate, after
      taking wage revisions into account. All the career categories in the Ministry of
      Health and affiliated public sector institutions were considered. RESULTS: Health
      workers' purchasing power is an important consideration in the development of
      strategies for health workforce development. This work explores the purchasing
      power variation of Mozambican public sector health workers, between 1999 and
      2007. In general, the calculated purchasing power increased for most careers
      under study, and the highest percentage increase was observed for the lowest
      remuneration careers, contributing in this way for a relative reduction in the
      difference between the higher and the lower salaries. CONCLUSION: These results
      seem to contradict a commonly held assumption that health sector pay has
      deteriorated over the years, and with substantial damage for the poorest. Further
      studies appear to be needed to design a more accurate methodology to better
      understand the evolution and impact of public sector health workers'
      remunerations across the years.

PMID- 22368758
TI  - The frequency and magnitude of growth failure in a group of HIV-infected children
      in Cameroon.
AB  - BACKGROUND: Growth impairment is a major manifestation of HIV infection in
      children and has been implicated as a major contributor to both morbidity and
      mortality. This study the first to be done in this setting, was aimed at
      comparing the growth of HIV infected children to that of non-infected children in
      two referral health facilities in Yaounde, Cameroon. METHODS: A prospective case
      control study was carried out on 39 HIV infected children in two referral
      hospitals and followed up for a period of 12 months. Anthropometric measurements
      were taken and the sociodemographic variables of mothers and infants noted.
      Thirty nine infected children (mean age 45.3 months +/- 41.6 SD) were age and sex
      matched with 39 non-infected children (mean age 44.4 +/- 40.7 months). RESULTS:
      Out of the 39 infected children, 26 (66.7%) had at least one of the three
      anthropometric indices (weight for height, weight for age, height for age) Z
      scores less than -2. Throughout follow-up, 20.5% of the infected children were
      wasted (weight to height Z score < -2) versus none in the control group, 56.4%
      underweight (weight for age Z score < -2) in the infected versus 2.6% in the
      control group, and 51.3% stunted (height for age Z score < -2) in contrast to
      5.1% in the control group. CONCLUSION: This study demonstrated that wasting;
      underweight and stunting are common findings in HIV- infected children, thus
      stressing the importance of anthropometry in the routine care of these children.

PMID- 22368759
TI  - From a dream to a resounding reality: the inception of a doctors union in Kenya.
AB  - After two grueling years of determination and resilience, the Kenyan doctors have
      formed a doctors' union. The Kenya Medical Practitioners, Pharmacists and
      Dentists Union(KMPDU)not only aims at agitating for better terms of service for
      its members, it also aims to influence the running of the Kenyan health sector
      and improve health services in Kenya. The union has been fully recognized by the
      Kenyan government and is engaging the government concerning various health sector
      policies besides improved terms and working conditions of the doctors in the
      country.

PMID- 22368760
TI  - Internal supravesical hernia - a rare cause of intestinal obstruction: report of
      two cases.
AB  - Supravesical hernias develop at the supravesical fossa between the remnants of
      the urachus and the left or right umbilical artery. They are exceptional and are
      often the cause of intestinal obstruction. We report two cases of surgically
      proven internal supravesical hernias presenting with small bowel obstruction.
      Abdominal computed tomography showed, for our first case, the relation of the
      incarcerated intestine anterior to and compressing the urinary bladder. We
      believe that the preoperative diagnosis of supravesical hernia by abdominal
      computed tomography is possible, as shown in our first case.

PMID- 22368761
TI  - First report of HIV-related oral manifestations in Mali.
AB  - INTRODUCTION: In 2004, the sudden availability of free antiretroviral therapy
      (ART in Mali, within the context of an already overburdened health care system
      created gaps in individual patient quality of care. The objective of this study
      was to determine the prevalence of HIV-related oral manifestations (OM) during
      the first month of ART therapy in a Malian health facility. METHODS: Medical
      records of adult patients who initiated ART regimens at the Gabriel Toure
      Hospital, Mali (2001 to 2008) were randomly identified. Multiple logistic
      regression models were used to evaluate the relationship between the presence of
      OM during the first month of ART and selected variables, including CD4 counts and
      WHO clinical staging at ART initiation. RESULTS: Out of 205 patients on ART (mean
      age 39 +/- 10 years), 71.0% were females and 36.1% had no formal education. 40.6%
      were in WHO clinical stage III. OM prevalence during the first month of HIV care
      was 31.4%, being oral candidiasis the commonest lesion. 73.2% and 82.5% of the
      patients with OM had CD4 count < 200 cells/mm3 and were classified as WHO
      clinical stage III or IV. WHO clinical stage III and VI patients had 5.4-fold
      increased odds of having any OM (both p< 0.01) when controlling for age,
      ethnicity, gender, marital status, and CD4 counts. CONCLUSION: OM detected in
      people with low CD4 count and WHO clinical stage III and IV at ART initiation
      suggested that they were very immune-compromised when initiating HIV care. Early
      identification of OM could improve the quality of care and guarantee the benefits
      of ART.

PMID- 22368762
TI  - Synergistic enhancement of the potency and selectivity of small molecule
      transcriptional inhibitors.
AB  - In spite of their considerable therapeutic potential, the development of highly
      potent and selective transcriptional inhibitors has proven elusive. We
      demonstrate that combinations of transcriptional inhibitors of erbB2 expression
      and existing therapeutic agents that target erbB2 activity and lifetime lead to a
      synergistic increase in activity, with dose reductions as high 30 fold compared
      to individual agents. The synergy is selective for erbB2 overexpressing cancer
      cells. These results highlight the potential of a generalizable approach that
      will improve the utility of transcriptional inhibitors as both biochemical tools
      and potential therapeutics.

PMID- 22368763
TI  - Small Molecule Inhibitors of Regulator of G Protein Signalling (RGS) Proteins.
AB  - Recently regulators of G protein signalling (RGS) proteins have emerged as
      potential therapeutic targets since they provide an alternative method of
      modulating the activity of GPCRs, the target of so many drugs. Inhibitors of RGS
      proteins must block a protein-protein interaction (RGS-Galpha), but also be cell
      and, depending on the therapeutic target, blood brain barrier permeable. A lead
      compound (1a) was identified as an inhibitor of RGS4 in a screening assay and
      this has now been optimised for activity, selectivity and solubility. The newly
      developed ligands (11b, 13) display substantial selectivity over the closely
      related RGS8 protein, lack the off-target calcium mobilisation activity of the
      lead 1a and have excellent aqueous solubility. They are currently being evaluated
      in vivo in rodent models of depression.

PMID- 22368764
TI  - The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type
      Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent
      Model of Parkinson's Disease.
AB  - T-type Ca(2+) channel inhibitors hold tremendous therapeutic potential for the
      treatment of pain, epilepsy, sleep disorders, essential tremor and other
      neurological disorders; however, a lack of truly selective tools has hindered
      basic research, and selective tools from the pharmaceutical industry are
      potentially burdened with intellectual property (IP) constraints. Thus, an MLPCN
      high-throughput screen (HTS) was conducted to identify novel T-type Ca(2+)
      channel inhibitors free from IP constraints, and freely available through the
      MLPCN, for use by the biomedical community to study T-type Ca(2+) channels. While
      the HTS provided numerous hits, these compounds could not be optimized to the
      required level of potency to be appropriate tool compounds. Therefore, a scaffold
      hopping approach, guided by SurflexSim, ultimately afforded ML218 (CID 45115620)
      a selective T-Type Ca(2+) (Ca(v)3.1, Ca(v)3.2, Ca(v)3.3) inhibitor (Ca(v)3.2,
      IC(50) = 150 nM in Ca(2+) flux; Ca(v)3.2 IC(50) = 310 nM and Ca(v)3.3 IC(50) =
      270 nM, respectively in patch clamp electrophysiology) with good DMPK properties,
      acceptable in vivo rat PK and excellent brain levels. Electrophysiology studies
      in subthalamic nucleus (STN) neurons demonstrated robust effects of ML218 on the
      inhibition of T-Type calcium current, inhibition of low threshold spike and
      rebound burst activity. Based on the basal ganglia circuitry in Parkinson's
      disease (PD), the effects of ML218 in STN neurons suggest a therapeutic role for
      T-type Ca(2+) channel inhibitors, and ML218 was found to be orally efficacious in
      haloperidol-induced catalepsy, a preclinical PD model, with comparable efficacy
      to an A(2A) antagonist, a clinically validated PD target. ML218 proves to be a
      powerful new probe to study T-Type Ca(2+) function in vitro and in vivo, and
      freely available.

PMID- 22368765
TI  - Label-free detection of G protein-SNARE interactions and screening for small
      molecule modulators.
AB  - G(i/o)-coupled presynaptic GPCRs are major targets in neuropsychiatric diseases.
      For example, presynaptic auto- or heteroreceptors include the D(2) dopamine
      receptor, H(3) histamine receptor, 5HT(1) serotonin receptors, M(4) acetylcholine
      receptors, GABA(B) receptors, Class II and III metabotropic glutamate receptors,
      opioid receptors, as well as many other receptors. These GPCRs exert their
      influence by decreasing exocytosis of synaptic vesicles. One mechanism by which
      they act is through direct interaction of the Gbetagamma subunit with members of
      the SNARE complex downstream of voltage-dependent calcium channels, and
      specifically with the C-terminus of SNAP25 and the H3 domain of syntaxin1A(1-3).
      Small molecule inhibitors of the Gbetagamma-SNARE interaction would allow the
      study of the relative importance of this mechanism in more detail. We have
      utilized novel, label-free technology to detect this protein-protein interaction
      and screen for several small molecule compounds that perturb the interaction,
      demonstrating the viability of this approach. Interestingly, the screen also
      produced enhancers of the Gbetagamma-SNARE interaction.

PMID- 22368766
TI  - SHAKE parallelization.
AB  - SHAKE is a widely used algorithm to impose general holonomic constraints during
      molecular simulations. By imposing constraints on stiff degrees of freedom that
      require integration with small time steps (without the constraints) we are able
      to calculate trajectories with time steps larger by approximately a factor of
      two. The larger time step makes it possible to run longer simulations. Another
      approach to extend the scope of Molecular Dynamics is parallelization.
      Parallelization speeds up the calculation of the forces between the atoms and
      makes it possible to compute longer trajectories with better statistics for
      thermodynamic and kinetic averages. A combination of SHAKE and parallelism is
      therefore highly desired. Unfortunately, the most widely used SHAKE algorithm (of
      bond relaxation) is inappropriate for parallelization and alternatives are
      needed. The alternatives must minimize communication, lead to good load
      balancing, and offer significantly better performance than the bond relaxation
      approach. The algorithm should also scale with the number of processors. We
      describe the theory behind different implementations of constrained dynamics on
      parallel systems, and their implementation on common architectures.

PMID- 22368768
TI  - Host-pathogen dynamics: it's complicated!

PMID- 22368767
TI  - Treponema denticola interactions with host proteins.
AB  - Oral Treponema species, most notably T. denticola, are implicated in the
      destructive effects of human periodontal disease. Progress in the molecular
      analysis of interactions between T. denticola and host proteins is reviewed here,
      with particular emphasis on the characterization of surface-expressed and
      secreted proteins of T. denticola involved in interactions with host cells,
      extracellular matrix components, and components of the innate immune system.

PMID- 22368769
TI  - The gut microbiome: scourge, sentinel or spectator?
AB  - The gut microbiota consists of trillions of prokaryotes that reside in the
      intestinal mucosa. This long-established commensalism indicates that these
      microbes are an integral part of the eukaryotic host. Recent research findings
      have implicated the dynamics of microbial function in setting thresholds for many
      physiological parameters. Conversely, it has been convincingly argued that
      dysbiosis, representing microbial imbalance, may be an important underlying
      factor that contributes to a variety of diseases, inside and outside the gut.
      This review discusses the latest findings, including enterotype classification,
      changes brought on by dysbiosis, gut inflammation, and metabolic mediators in an
      attempt to underscore the importance of the gut microbiota for human health. A
      cautiously optimistic idea is taking hold, invoking the gut microbiota as a
      medium to track, target and treat a plethora of diseases.

PMID- 22368771
TI  - Virulence factors and antibiotic susceptibility in enterococci isolated from oral
      mucosal and deep infections.
AB  - OBJECTIVE: This study evaluates the presence of virulence factors and antibiotic
      susceptibility among enterococcal isolates from oral mucosal and deep infections.
      METHODS: Forty-three enterococcal strains from oral mucosal lesions and 18 from
      deep infections were isolated from 830 samples that were sent during 2 years to
      Oral Microbiology, University of Gothenburg, for analysis. The 61 strains were
      identified by 16S rDNA, and characterized by the presence of the virulence genes
      efa A (endocarditis gene), gel E (gelatinase gene), ace (collagen binding antigen
      gene), asa (aggregation substance gene), cyl A (cytolysin activator gene) and esp
      (surface adhesin gene), tested for the production of bacteriocins and presence of
      plasmids. MIC determination was performed using the E-test method against the
      most commonly used antibiotics in dentistry, for example, penicillin V,
      amoxicillin and clindamycin. Vancomycin was included in order to detect
      vancomycin-resistant enterococci (VRE) strains. RESULTS: Sixty strains were
      identified as Enterococcus faecalis and one as Enterococcus faecium. All the
      virulence genes were detected in more than 93.3% (efa A and esp) of the E.
      faecalis strains, while the presence of phenotypic characteristics was much lower
      (gelatinase 10% and hemolysin 16.7%). Forty-six strains produced bacteriocins and
      one to six plasmids were detected in half of the isolates. CONCLUSIONS:
      Enterococcal strains from oral infections had a high virulence capacity, showed
      bacteriocin production and had numerous plasmids. They were generally susceptible
      to ampicillins but were resistant to clindamycin, commonly used in dentistry, and
      no VRE-strain was found.

PMID- 22368772
TI  - Cerebral venous thrombosis: diagnosis dilemma.
AB  - Cerebral venous thrombosis is increasing common disease in daily practice with
      sharing clinical nonspecific symptoms. This disorder is potentially lethal but
      treatable, oftenly it was overlooked in both clinical and radiologic in routine
      practice. Whenever, clinical suspected, prompt investigation by noninvasive
      imaging Magnetic resonance (MR) or advanced modilities such as cerebral venous
      thrombosis (CVT), MRV (MR Venography) will helpful in prompt diagnosis and
      treatment. These imaging modalities may reveal either direct sign (visualization
      of intraluminal clot) and indirect signs (paranchymatous change, intracranial
      hemorrhage). By using of effective treatment will improve the prognosis of the
      patient. This review summarizes insights into etiology, incidence, imaging
      modalities and current of the treatment.

PMID- 22368773
TI  - Evoked potentials in pediatric cerebral malaria.
AB  - Cortical evoked potentials (EP) provide localized data regarding brain function
      and may offer prognostic information and insights into the pathologic mechanisms
      of malaria-mediated cerebral injury. As part of a prospective cohort study, we
      obtained somatosensory evoked potentials (SSEPs) and brainstem auditory EPs
      (AEPs) within 24 hours of admission on 27 consecutive children admitted with
      cerebral malaria (CM). Children underwent follow-up for 12 months to determine if
      they had any long term neurologic sequelae. EPs were obtained in 27 pediatric CM
      admissions. Two children died. Among survivors followed an average of 514 days,
      7/25 (28.0%) had at least one adverse neurologic outcome. Only a single subject
      had absent cortical EPs on admission and this child had a good neurologic
      outcome. Among pediatric CM survivors, cortical EPs are generally intact and do
      not predict adverse neurologic outcomes. Further study is needed to determine if
      alterations in cortical EPs can be used to predict a fatal outcome in CM.

PMID- 22368775
TI  - Subacute neuronopathy in a young man: a possible association with tetracycline
      treatment.
AB  - A young man with subacute neuronopathy following tetracycline treatment is
      described. The symptoms started as a sensory dorsal root affection but by time
      also involved motor nerves. He developed a severe sensory ataxia with
      pseudoathetotic movements. Other possible aetiologies were scrutinized and
      excluded. Tetracycline induced neuronopathy is hitherto not reported in the
      literature. We propose a possible association between treatment with tetracycline
      and the development of sensory neuronopathy in this patient.

PMID- 22368774
TI  - Obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) affects millions of Americans and is estimated to
      be as prevalent as asthma and diabetes. Given the fact that obesity is a major
      risk factor for OSA, and given the current global rise in obesity, the prevalence
      of OSA will increase in the future. Individuals with sleep apnea are often
      unaware of their sleep disorder. It is usually first recognized as a problem by
      family members who witness the apneic episodes or is suspected by their primary
      care doctor because of the individual's risk factors and symptoms. The vast
      majority remain undiagnosed and untreated, despite the fact that this serious
      disorder can have significant consequences. Individuals with untreated OSA can
      stop breathing hundreds of times a night during their sleep. These apneic events
      can lead to fragmented sleep that is of poor quality, as the brain arouses
      briefly in order for the body to resume breathing. Untreated, sleep apnea can
      have dire health consequences and can increase the risk of hypertension,
      diabetes, heart disease, and heart failure. OSA management has also become
      important in a number of comorbid neurological conditions, including epilepsy,
      stroke, multiple sclerosis, and headache. Diagnosis typically involves use of
      screening questionnaires, physical exam, and an overnight polysomnography or a
      portable home study. Treatment options include changes in lifestyle, positive
      airway pressure, surgery, and dental appliances.

PMID- 22368776
TI  - Importance of differentiating Mycobaterium bovis in tuberculous meningitis.
AB  - The aim of the article is to describe the principal findings among patients with
      M.tuberculosis and M. bovis CNS infection. Mycobacterium tuberculosis is one of
      the most common infectious agents that cause death and neurological sequelae
      around the world. Most of the complications of CNS TB can be attributed to a
      delay in the diagnosis. Unfortunately, there are no specific diagnostic tools to
      support an early diagnosis. Other prognostic factors different from delay in
      treatment have not been identified. Clinical, radiological and laboratory
      characteristics were analyzed retrospectively from the medical files of all the
      patients admitted with the diagnoses of tuberculosis. Of 215 patients admitted
      with systemic tuberculosis, 64 (30%) had a neurological infection. Positive
      cultures were found in 54 (84%) cases, 18 (33%) in the CSF and the rest in other
      fluids or tissues. Adenosin deaminase (ADA) enzyme determination was more
      sensitive than M. tuberculosis PCR in the CSF for supporting an early diagnosis.
      In addition to a later clinical stage and treatment lag, positive CSF cultures
      (P=0.001) and the presence of M. bovis (P=0.020) were prognostic factors for a
      worse outcome. Neither older age, the presence of tuberculomas versus meningeal
      enhancement, or HIV co-infection, was associated to a worse prognosis. The
      isolation of M. bovis subspecies was more common that previously reported, and it
      was associated to the development of parenchymal lesions (P=0.032) when compared
      to M. tuberculosis. In this study, positive CSF cultures for M. tuberculosis and
      further identifying M. bovis species were additional prognostic factors for worse
      outcome. Positive cultures in systemic fluids other than CSF, even when the
      patient had no obvious systemic manifestations, and ADA determination in the CSF
      were noteworthy diagnostic tools for the diagnosis.

PMID- 22368770
TI  - The Drosophila melanogaster host model.
AB  - The deleterious and sometimes fatal outcomes of bacterial infectious diseases are
      the net result of the interactions between the pathogen and the host, and the
      genetically tractable fruit fly, Drosophila melanogaster, has emerged as a
      valuable tool for modeling the pathogen-host interactions of a wide variety of
      bacteria. These studies have revealed that there is a remarkable conservation of
      bacterial pathogenesis and host defence mechanisms between higher host organisms
      and Drosophila. This review presents an in-depth discussion of the Drosophila
      immune response, the Drosophila killing model, and the use of the model to
      examine bacterial-host interactions. The recent introduction of the Drosophila
      model into the oral microbiology field is discussed, specifically the use of the
      model to examine Porphyromonas gingivalis-host interactions, and finally the
      potential uses of this powerful model system to further elucidate oral bacterial
      host interactions are addressed.

PMID- 22368777
TI  - Developmental regulation of CB1-mediated spike-time dependent depression at
      immature mossy fiber-CA3 synapses.
AB  - Early in postnatal life, mossy fibres (MF), the axons of granule cells in the
      dentate gyrus, release GABA which is depolarizing and excitatory. Synaptic
      currents undergo spike-time dependent long-term depression (STD-LTD) regardless
      of the temporal order of stimulation (pre versus post and viceversa). Here we
      show that at P3 but not at P21, STD-LTD, induced by negative pairing, is mediated
      by endocannabinoids mobilized from the postsynaptic cell during spiking-induced
      membrane depolarization. By diffusing backward, endocannabinoids activate
      cannabinoid type-1 (CB1) receptors probably expressed on MF. Thus, STD-LTD was
      prevented by CB1 receptor antagonists and was absent in CB1-KO mice. Consistent
      with these data, in situ hybridization experiments revealed detectable level of
      CB1 mRNA in the granule cell layer at P3 but not at P21. These results indicate
      that CB1 receptors are transiently expressed on immature MF terminals where they
      counteract the enhanced neuronal excitability induced by the excitatory action of
      GABA.

PMID- 22368778
TI  - Characterizing the role of rice NRAMP5 in Manganese, Iron and Cadmium Transport.
AB  - Metals like manganese (Mn) and iron (Fe) are essential for metabolism, while
      cadmium (Cd) is toxic for virtually all living organisms. Understanding the
      transport of these metals is important for breeding better crops. We have
      identified that OsNRAMP5 contributes to Mn, Fe and Cd transport in rice. OsNRAMP5
      expression was restricted to roots epidermis, exodermis, and outer layers of the
      cortex as well as in tissues around the xylem. OsNRAMP5 localized to the plasma
      membrane, and complemented the growth of yeast strains defective in Mn, Fe, and
      Cd transport. OsNRAMP5 RNAi (OsNRAMP5i) plants accumulated less Mn in the roots,
      and less Mn and Fe in shoots, and xylem sap. The suppression of OsNRAMP5 promoted
      Cd translocation to shoots, highlighting the importance of this gene for Cd
      phytoremediation. These data reveal that OsNRAMP5 contributes to Mn, Cd, and Fe
      transport in rice and is important for plant growth and development.

PMID- 22368779
TI  - Membrane Compartment Occupied by Can1 (MCC) and Eisosome Subdomains of the Fungal
      Plasma Membrane.
AB  - Studies on the budding yeast Saccharomyces cerevisiae have revealed that fungal
      plasma membranes are organized into different subdomains. One new domain termed
      MCC/eisosomes consists of stable punctate patches that are distinct from lipid
      rafts. The MCC/eisosome domains correspond to furrows in the plasma membrane that
      are about 300 nm long and 50 nm deep. The MCC portion includes integral membrane
      proteins, such as the tetraspanners Sur7 and Nce102. The adjacent eisosome
      includes proteins that are peripherally associated with the membrane, including
      the BAR domains proteins Pil1 and Lsp1 that are thought to promote membrane
      curvature. Genetic analysis of the MCC/eisosome components indicates these
      domains broadly affect overall plasma membrane organization. The mechanisms
      regulating the formation of MCC/eisosomes in model organisms will be reviewed as
      well as the role of these plasma membrane domains in fungal pathogenesis and
      response to antifungal drugs. 

PMID- 22368780
TI  - Variation in models of care delivery for children undergoing congenital heart
      surgery in the United States.
AB  - Limited data are available regarding contemporary models of care delivery for
      patients undergoing congenital heart surgery. The purpose of this survey was to
      evaluate current US practice patterns in this patient population. Cross-sectional
      evaluation of US centers caring for patients undergoing congenital heart surgery
      was performed using an Internet-based survey. Data regarding postoperative care
      were collected and described overall and were compared in centers with a
      pediatric intensive care unit (PICU) versus dedicated pediatric cardiac intensive
      care unit (CICU). A total of 94 (77%) of the estimated 122 US centers performing
      congenital heart surgery participated in the survey. The majority (79%) of
      centers were affiliated with a university. Approximately half were located in a
      free-standing children's hospital and half in a children's hospital in a
      hospital. Fifty-five percent provided care in a PICU versus a CICU. A combination
      of cardiologists and/or critical care physicians made up the largest proportion
      of physicians primarily responsible for postoperative care. Trainee involvement
      most often included critical care fellows (53%), pediatric residents (53%), and
      cardiology fellows (47%). Many centers (76%) also used physician extenders. In
      centers with a CICU, there was greater involvement of cardiologists and
      physicians with dual training (cardiology and critical care), fellows versus
      residents, and physician extenders. Results of this survey demonstrate variation
      in current models of care delivery used in patients undergoing congenital heart
      surgery in the United States. Further study is necessary to evaluate the
      implications of this variability on quality of care and patient outcomes. 

PMID- 22368781
TI  - Regulation of colon cancer recurrence and development of therapeutic strategies.
AB  - Recurrence of colon cancer still remains a major issue which affects nearly 50%
      of patients treated by conventional therapeutics. Although the underlying
      causative factor(s) is not fully understood, development of drug-resistance has
      been associated with induction of cancer stem or stem-like cells (CSCs) which
      constitute a small sub-population of tumor cells known to be highly resistant to
      chemotherapy. In fact, the discovery of CSCs in a variety of tumors (including
      colon cancer) has changed the view of carcinogenesis and therapeutic strategies.
      Emerging reports have indicated that to improve patient outcomes, conventional
      anticancer therapies should be replaced with specific approaches targeting CSCs.
      Thus, therapeutic strategies that specifically target CSCs are being sought to
      reduce the risk of relapse and metastasis. In order to specifically target colon
      CSCs (while sparing somatic intestinal stem cells), it is critical to identify
      unique deregulated pathways responsible for self-renewal of CSCs and colon cancer
      recurrence. Colon CSCs present a unique opportunity to better understand the
      biology of solid tumors. Thus, a better understanding of the clinical signs and
      symptoms of colon cancer patients (undergoing surgery or chemotherapy) during
      perioperative periods, along with the underlying regulatory events affecting the
      stem/progenitor cell self-renewal and differentiation of colon epithelial cells,
      is of immense importance. In this review we discuss the implication of clinical
      factors and the emerging role of CSCs during recurrence of colon cancer along
      with the development of new therapeutic strategies involving the use of natural
      agents.

PMID- 22368782
TI  - Electrical bioimpedance and other techniques for gastric emptying and motility
      evaluation.
AB  - The aim of this article is to identify non-invasive, inexpensive, highly
      sensitive and accurate techniques for evaluating and diagnosing gastric diseases.
      In the case of the stomach, there are highly sensitive and specific methods for
      assessing gastric motility and emptying (GME). However, these methods are
      invasive, expensive and/or not technically feasible for all clinicians and
      patients. We present a summary of the most relevant international information on
      non-invasive methods and techniques for clinically evaluating GME. We
      particularly emphasize the potential of gastric electrical bioimpedance (EBI).
      EBI was initially used mainly in gastric emptying studies and was essentially
      abandoned in favor of techniques such as electrogastrography and the gold
      standard, scintigraphy. The current research evaluating the utility of gastric
      EBI either combines this technique with other frequently used techniques or uses
      new methods for gastric EBI signal analysis. In this context, we discuss our
      results and those of other researchers who have worked with gastric EBI. In this
      review article, we present the following topics: (1) a description of the oldest
      methods and procedures for evaluating GME; (2) an explanation of the methods
      currently used to evaluate gastric activity; and (3) a perspective on the newest
      trends and techniques in clinical and research GME methods. We conclude that
      gastric EBI is a highly effective non-invasive, easy to use and inexpensive
      technique for assessing GME.

PMID- 22368783
TI  - Encapsulated islets transplantation: Past, present and future.
AB  - Islet transplantation could become an ideal treatment for severe diabetes to
      prevent hypoglycemia shock and irreversible diabetic complications, once some of
      the major and unresolved obstacles are overcome, including limited donor supplies
      and side effects caused by permanent immunosuppressant use. Approximately 30
      years ago, some groups succeeded in improving the blood glucose of diabetic
      animals by transplanting encapsulated islets with semi-permeable membranes
      consisting of polymer. A semi-permeable membrane protects both the inner islets
      from mechanical stress and the recipient's immune system (both cellular and
      humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen,
      glucose, hormones and wastes, i.e., immune-isolation. This device, which enables
      immune-isolation, is called encapsulated islets or bio-artificial pancreas.
      Encapsulation with a semi-permeable membrane can provide some advantages: (1)
      this device protects transplanted cells from the recipient's immunity even if the
      xenogeneic islets (from large animals such as pig) or insulin-producing cells are
      derived from cells that have the potential for differentiation (some kinds of
      stem cells). In other words, the encapsulation technique can resolve the problem
      of limited donor supplies; and (2) encapsulation can reduce or prevent chronic
      administration of immunosuppressants and, therefore, important side effects
      otherwise induced by immunosuppressants. And now, many novel encapsulated islet
      systems have been developed and are being prepared for testing in a clinical
      setting.

PMID- 22368785
TI  - Bolt from the blue: Basal ganglion bleed following lightning strike.

PMID- 22368786
TI  - The sub-pial resection technique for intrinsic tumor surgery.
AB  - BACKGROUND: The technique of sub-pial resection, first described in the early
      1900s, was later refined by Penfield and Jasper for removal of supratentorial
      epileptic cortex. This technique has not been widely adopted for intrinsic tumor
      resection, for which the most widely used technique involves piecemeal aspiration
      of the tumor. This technique of "staying within the tumor" results in persistent
      bleeding, with obscuration of the tumor/brain interface, potentially yielding
      less than satisfactory results. In our experience, the sub-pial technique is
      useful for resections of supratentorial intrinsic tumor. We report the use of sub
      pial resection technique and present illustrative cases. METHODS: The sub-pial
      resection technique is described along with important clinical decision-making
      guidelines. Representative cases are presented to discuss application of the sub
      pial technique and to demonstrate surgical results. RESULTS: The sub-pial
      technique preserves the pia during cortical resections and makes it easier to
      protect and identify normal anatomy, including sulci, gyri, cranial nerves, and
      major vascular structures. This reduces bleeding, making surgery safer and more
      efficient. In most cases, an en bloc resection can be accomplished, permitting
      more accurate histopathology and more extensive tissue acquisition for research
      purposes. CONCLUSION: The sub-pial technique can be incorporated into strategies
      for supratentorial intrinsic tumor resections, including temporal, frontal,
      occipital, and insular tumors, at para-Sylvian or para-insular-sulcus locations.

PMID- 22368784
TI  - Host-microbial interactions and regulation of intestinal epithelial barrier
      function: From physiology to pathology.
AB  - The gastrointestinal tract is the largest reservoir of commensal bacteria in the
      human body, providing nutrients and space for the survival of microbes while
      concurrently operating mucosal barriers to confine the microbial population. The
      epithelial cells linked by tight junctions not only physically separate the
      microbiota from the lamina propria, but also secrete proinflammatory cytokines
      and reactive oxygen species in response to pathogen invasion and metabolic stress
      and serve as a sentinel to the underlying immune cells. Accumulating evidence
      indicates that commensal bacteria are involved in various physiological functions
      in the gut and microbial imbalances (dysbiosis) may cause pathology. Commensal
      bacteria are involved in the regulation of intestinal epithelial cell turnover,
      promotion of epithelial restitution and reorganization of tight junctions, all of
      which are pivotal for fortifying barrier function. Recent studies indicate that
      aberrant bacterial lipopolysaccharide-mediated signaling in gut mucosa may be
      involved in the pathogenesis of chronic inflammation and carcinogenesis. Our
      perception of enteric commensals has now changed from one of opportunistic
      pathogens to active participants in maintaining intestinal homeostasis. This
      review attempts to explain the dynamic interaction between the intestinal
      epithelium and commensal bacteria in disease and health status.

PMID- 22368787
TI  - Minimally invasive removal of a giant extradural lumbar foraminal schwannoma.
AB  - BACKGROUND: Purely extradural lumbar schwannomas are rare lesions. Resection
      traditionally requires an open laminectomy and ipsilateral complete facectomy.
      Recent reports have demonstrated safety and efficacy of removal of these tumors
      using mini-open access devices with expandable retractors. We report a case of a
      giant L3 schwannoma successfully resected through a minimally invasive approach
      using the non-expandable Spotlight tubular retrator (Depuy Spine). CASE
      DESCRIPTION: A 77-year-old woman presented with a history of chronic right leg
      pain, paresthesias and proximal right leg weakness. Magnetic Resonance imaging
      (MRI) scan revealed a large dumbbell-shaped extradural foraminal lesion at the L3
      L4 level with significant extraforaminal extension. The patient underwent a
      minimally invasive gross total resection (GTR) of the tumor using an 18-mm
      Spotlight tubular retractor system. Pathology confirmed the lesion to be a benign
      schwannoma. Postoperatively, the patient's symptoms resolved and she was
      discharged from the hospital on the second postoperative day. Postoperative MRI
      showed no residual tumor. The patient returned to normal activities after 2 weeks
      and remained asymptomatic with no neurological deficits at final 6 months follow
      up. CONCLUSION: Giant lumbar extradural schwannomas can be safely and completely
      resected using minimally invasive surgery without the need for facectomy or
      subsequent spinal fusion.

PMID- 22368790
TI  - Pseudo-Auer rods in a patient with newly diagnosed IgG myeloma.

PMID- 22368789
TI  - Distress among Indigenous North Americans: Generalized and Culturally Relevant
      Stressors.
AB  - Stress process and life-course models of mental distress emphasize socio-cultural
      and historical processes that influence stress exposure and the impact of stress
      on mental health outcomes. Drawing from these theoretical orientations as well as
      concepts from the historical trauma literature, we examine the effects of
      culturally relevant and more generalized sources of stress on distress among
      North American Indigenous adults, and tests for the potential cumulative and
      interactive effects of stress on distress across the life-course via self
      reported early childhood and adult/contemporary stressors. Results of OLS
      regression analyses reveal positive, significant associations between general
      stressors and distress as well as culturally-meaningful stressors and distress.
      In addition, we found evidence of the accumulating and interactive impact of
      stress on psychological distress.

PMID- 22368791
TI  - Retraction. Genome-wide assessment of copy number variations in early-onset
      Alzheimer's disease.

PMID- 22368792
TI  - Effects of major depression on obesity.

PMID- 22368793
TI  - [Construction and expression of recombinant adenovirus encoding MDA-7/IL-24 and
      its inhibitory effect on proliferation in human hepatocellular carcinoma cells].
AB  - AIM: To construct recombinant plasmid and adenovirus harboring MDA-7 gene, and to
      investigate its biological function on the proliferation of human hepatocellular
      carcinoma cells. METHODS: The MDA-7 fragments from the T vectors were inserted
      into pCDNA-3 vector to construct expression plasmids named pCDNA3-MDA-7. To
      determine its effects on the proliferation of HCC cells, transfected the
      expression vector into cells and tested the ability of colony formation in cancer
      cells. Simultaneously, constructed recombinant adenovirus expressing MDA-7, and
      detected its effect on the proliferation of HCC cells by using MTT assay.
      RESULTS: Successfully constructed plasmid- and adenovirus-based system to express
      MDA-7. The data of colony formation assay and M'T test showed that MDA-7 can
      obviously suppress cell growth in HCC cells. CONCLUSION: MDA-7 may function as
      tumor suppressor in HCC cells, and the adenovirus-mediated MDA-7 can be a novel
      strategy for the anti-HCC therapy. Our study established the foundation for
      future research on the effect of MDA-7 in HCC.

PMID- 22368794
TI  - [Imbalance of Thl7/Treg cell ratio in peripheral blood of patients with nasal
      polyposis and its clinical significance].
AB  - AIM: To observe the distribution of Thl7 cells and Foxp3 CD4 * CD25 regulatory T
      cells in peripheral blood of patients with nasal polyposis(NP) and their
      correlation with clinical patients' condition, and to explore the role of
      Thl7/Treg cell ratio imbalance in pathogenesis of nasal polyposis and
      significance. METHODS: The frequencies of Thl7 cells and Treg cells were
      determined in 46 patients with NP and 10 controls by flow cytometry. The 46
      patients were divided into two groups according to endoscopy score and CT score:
      the 1 group (endoscopy score: 2-8 scores; CT score: 3 -10 scores, n = 23) and the
      2 group (endoscopy score: 8 -12 scores; CT score: 10 -19 scores, n = 23).
      RESULTS: Thl7 cells were significantly higher in the blood of patients with NP
      compared with the control group (P<0.01), and the percentage was higher in the 2
      group than the 1 group (P<0.05). The frequency of Treg cells was significantly
      decreased in patients with NP compared to the control group (P < 0. 01), whereas
      the difference between two groups was not significant. The ratio of Thl7/Treg
      cells was highest in the 2 group (P < 0.01), lower in the 1 group (P<0.01) and
      lowest in control subjects, and the differences were also significant between two
      groups (P<0.05). Furthermore, it was confirmed that the ratio of Thl7/Treg
      positively correlated with endoscopy score and CT score (P <. 0.01). CONCLUSION:
      The imbalance of Thl7/Treg cell ratio characterized by increased Thl7 cells and
      decreased Treg cells exists in peripheral blood of NP patients and may play an
      important role in the onset and development of NP. The degree of Thl7/Treg cell
      imbalance may associate with clinical presentation.

PMID- 22368795
TI  - [The correlation between the level of serum VEGF and bFGF with metastasis and
      prognosis of osteosarcoma].
AB  - AIM: To investigate the correlation between the level of serum VEGF and bFGF with
      metastasis and re- currence of osteosarcoma. METHODS: 52 patients with
      osteosarcoma and 60 healthy people as control group were selected. The serum
      contents of VEGF and bFGF were determined with ELISA before and after operation.
      RESULTS: The serum contents of VEGF and bFGF before operation were significantly
      higher than that in control group ( P < 0.01). The serum contents of VEGF and
      bFGF after operation descreased significantly but were significantly higher than
      that in control group(P<0. 01). The serum contents of VEGF and bFGF before
      operation were positively related to the size of primarily tumor, Enneking type
      and tumor differentiation(P<0.05). The serum contents of VEGF and bFGF before and
      after operation were different significantly between recurrence and metastasis
      positive group with recurrence and metastasis negative group ( P < 0. 01). The
      Cox proportional hazards model showed that the serum contents of VEGF and bFGF
      before and after operation were an independent factor of the recurrence and
      metastasis for osteosar- coma patients after operative ( P <0. 01). CONCLUSION:
      The serum contents of VEGF and bFGF before and after operation can offer valuable
      assessments in evaluation of progression and metastasis prognosis.

PMID- 22368796
TI  - [The influence of two kinds of crown margin designs on MMP-8 and TIMP-1 levels in
      gingival crevicular fluid ].
AB  - AIM: To explore the influence of two kinds of crown margin designs on MMP-8 and
      TIMP-1 levels in gingival crevicular fluid(GCF). METHODS: 16 cases of patients
      who needed full crowns were divided randomly into two groups: subgingival group
      and gingival crest group. The GCF were taken before tooth preparation, one month,
      three months and six months after crown placement. The levels of MMP-8 and TIMP-1
      in GCF were determined by ELISA. RESULTS: The levels of MMP-8 and TIMP-1 in GCF
      before tooth preparation made as baseline. The level of MMP-8 at one month after
      crown placement in subgingival group was higher than the baseline ( P <0. 05) and
      contiue increasing at three months after crown placement. The level of MMP-8 at
      six months after crown placement in subgingival group decreased, but it was
      higher than the baseline(P<0.05). In gingival crest group, atfer inserting
      crowns, the levels of MMP-8 and TIMP-1 was no signifieantly change. In two
      gourps, atfer inserting crowns, the levels of MMP-8 and TIMP-1 signifieantly
      increased. The level of MMP-8 in subgingival group was higher than that in
      gingival crest group at all times and the level of TIMP-1 in subgingival group
      was lower than that in gingival crest group. CONCLUSION: Gingival crest crown
      margin design is more fvourable to the effect of MMP-8 and TIMP-1 in maintaining
      the health and the regular remodeling of the periodontium.

PMID- 22368798
TI  - HPV: a danger at any age.

PMID- 22368797
TI  - [Study of pancreases beta-cell function in first-degree relatives of type 2
      diabetes patients].
AB  - AIM: To investig the pancreases beta-cell function in no-diabetic first-degree
      relatives of type 2 diabetes mellitus( FDR) patients. METHODS: Collect T2DM first
      degree relatives, and divided them into three groups:no-diabetes group with
      normal sugar tolerance (NGT); no-diabetes with abnormal sugar tolerance (IGT);
      new-confirmed T2DM. apart from that three group patients, 30 normal people with
      no-related disease risks were also collected as normal control (NC). All four
      groups of patients were experienced with intravenous glucose tolerance test
      (IVGTT) and counting the first phase of pancreases function by statistic AIR35
      and insulin sensitive index (ISI). RESULTS: New-confirmed T2DM patients with the
      significantly abnormal statistic results about AIR3.5 and ISI, while NGT patients
      had the abnormal results compared with normal control group but better than T2DM
      patients. CONCLUSION: Compared with normal group patients, NGT group appeared
      decrease of pancreases first phase secretes and insulin resistance but not
      aggravate enough to induce type 2 diabetes.

PMID- 22368799
TI  - Don't take echinacea if you're allergic to ragweed.

PMID- 22368800
TI  - Dental do's & don'ts: how to keep your teeth healthy without going broke.

PMID- 22368801
TI  - [Equivocal quintessence. Spiritual alchemy and counterfeit money in 16th-century
      Spain].
AB  - One of the main obsessions of the early modern era was that of determining the
      notions of true and false, in order to apply them to various fields of knowledge
      and thus establish the divide between the lawful and unlawful. This trend was to
      have a particular impact on the fields of religion and science, where it became
      necessary to distinguish not only between true and false spirits, relics or
      miracles, but also between genuine and fake astrologers and alchemists. Situated
      in the middle ground between idealism and materialism, alchemy was prime
      territory for such tensions, as was demonstrated by a trial held in 1593 at the
      Jeronymite monastery of Santa Enracia in Saragossa, whose prior accused a friar
      of making "silver out of smoke and jewels from goblins".

PMID- 22368802
TI  - [Autopsies of the real: resurrecting the dead].
AB  - The sense of the real, or the material - the dead body - as an inextricable part
      of the sacred does not disappear in the secular environment of the nineteenth and
      twentieth centuries. This article analyzes specific humanitarian narratives
      centered on the practice of autopsy and mummification, in which the traces of
      Catholicism act as a kind of spectral discourse of the imagination, where the
      real is configured in forms of the uncanny, the monstrous or the sacred.

PMID- 22368803
TI  - Proceedings of the III International Congress on Aromatic and Medicinal Plants.
      April 13-15, 2011, Cagliari, Italy.

PMID- 22368804
TI  - [A case of wheat-dependent exercise-induced anaphylaxis following the use of
      hydrolyzed wheat-containing soap other than "Chano Shizuku"].

PMID- 22368805
TI  - Cyril Harold Wolpe (1925-26 July 2011).

PMID- 22368806
TI  - Nathan Cirota (8 December 1944-6 June 2011).

PMID- 22368807
TI  - Computed tomography screening for coronary artery calcium in asymptomatic
      individuals.

PMID- 22368808
TI  - Evaluation of second-generation drug-eluting stents.

PMID- 22368809
TI  - Using of MRI in carotid artery plaque detection.

PMID- 22368810
TI  - [The impact of N, N-dimethylacetamide on the health of workers].
AB  - OBJECTIVE: To explore the hepatic toxicity and the exposure biomarkers of N, N
      Dimethylacetamide. METHODS: One hundred forty five objects were chosen by
      stratified random sampling method. The investigation was performed using
      questionnaire and physical examination. The air concentrations of DMAC in the
      workshops were monitored. The urine samples were collected and analyzed after
      work everyday or at the weekend. The correlation between the air concentrations
      of DMAC in the workshops and the concentrations of urinary NMAC wee analyzed by
      regression. RESULTS: The air concentration of DMAC in the spinning workshop was
      higher than others. The morbidity of abnormal hepatic function was 12.4%, 61.1%
      of workers with abnormal hepatic function appeared in one year after exposure to
      DMAC in the workshops ( r=0.44, P<0.01). CONCLUSION: The abnormal heptic function
      was found in workers exposed to DMAC for short period. The concentration of
      urinary NMAC can serve as the exposure biomarker of DMAC.

PMID- 22368811
TI  - The Garden State just got greener: New Jersey is  the fourteenth state in the
      nation to legalize medical marijuana.

PMID- 22368814
TI  - [A vicious circle: implementation of the law on migrant    Gypsies in Prague].

PMID- 22368816
TI  - New approaches to old problems: The well-being of the population of    Russia
      from 1821 to 1910 as measured by physical stature.

PMID- 22368817
TI  - On the biological standard of living in Russia and the Soviet Union.

PMID- 22368818
TI  - Tall tales: anthropometric measures of well-being in imperial Russia and the
      Soviet Union, 1821-1960.

PMID- 22368819
TI  - The great leap upwards: anthropometric data and indicators of crises and secular
      change in Soviet welfare levels, 1880-1960.

PMID- 22368821
TI  - An observation on sludge granulation in an enhanced biological phosphorus removal
      process.
AB  - A sequencing batch reactor (SBR) seeded with flocculated sludge and fed with
      synthetic wastewater was operated for an enhanced biological phosphorus removal
      (EBPR) process. Eight weeks after reactor startup, sludge granules were observed.
      The granules had a diameter of 0.5 to 3.0 mm and were brownish in color and
      spherical or ellipsoidal in shape. No significant change was observed in sludge
      granule size when operational pH was changed from 7 to 8. The 208-day continuous
      operation of the SBR showed that sludge granules were stably maintained with a
      sludge volume index (SVI) between 30 to 55 mL/g while securing a removal
      efficiency of 83% for carbon and 97% for phosphorus. Fluorescent in situ
      hybridization (FISH) confirmed the enrichment of polyphosphate accumulating
      organisms (PAOs) in the SBR. The observations of sludge granulation in this study
      encourage further studies in the development of granules-based EBPR process.

PMID- 22368822
TI  - Marine macrophytes as effective lead biosorbents.
AB  - Several species of seagrass and marine macrophytes were investigated for their
      biosorption performance in the removal of lead from aqueous solution. The effect
      of pH on the equilibrium of the seagrass Cymodocea nodosa as a biosorbent also
      was studied. It was found that increasing pH increased lead biosorption, with a
      maximum uptake of approximately 140 mg/g in the range pH 3.3 to 5. Equilibrium
      data at different pH levels were successfully fitted to competitive equilibrium
      models. In addition, the seaweeds belonging to different phyla (i.e.,
      Chlorophyta, Heterokontophyta, and Rhodophyta) were studied for the effect of
      their structure on equilibrium at a constant pH 5. The brown algae
      (Heterokontophyta) showed the highest potential for lead sorption, with a maximum
      uptake of 220 mg/g for C. compressa and 140 mg/g for S. lomentaria. The green
      algae (Chlorophyta) showed lead uptake in the range 40 to 90 mg/g, and the red
      algae (Rhodophyta) was least effective, with uptake in the range 10 to 40 mg/g.

PMID- 22368823
TI  - Anaerobic and aerobic transformations affecting stability of dewatered sludge
      during long-term storage in a lagoon.
AB  - The goal of this work was to study long-term behavior of anaerobically digested
      and dewatered sludge (biosolids) in a lagoon under anaerobic and aerobic
      conditions to determine the stability of the final product as an indicator of its
      odor potential. Field lagoons were sampled to estimate spatial and temporal
      variations in the physical-chemical properties and biological stability
      characteristics such as volatile solids content, accumulated oxygen uptake, and
      soluble protein content and odorous compound assessment. The analyses of
      collected data suggest that the surface layer of the lagoon (depth of above 0.15
      m) undergoes long-term aerobic oxidation resulting in a higher degree of
      stabilization in the final product. The subsurface layers (depth 0.15 m below the
      surface and deeper) are subjected to an anaerobic environment where the
      conditions favor the initial rapid organic matter degradation within
      approximately the first year, followed by slow degradation.

PMID- 22368824
TI  - Investigating phosphorus limitation in a fixed bed filter with phosphorus and
      nitrogen profile measurements.
AB  - In 2000, the European Union adopted the European Water Framework Directive (WFD)
      (European Commission, 2000). The WFD focuses on increasingly stringent nutrient
      standards including ultra low nitrogen (< 2.2 mg N-total/L) and phosphorus
      concentrations (< 0.15 mg total phosphorus/L) in receiving surface waters and in
      relevant point sources like wastewater treatment plant (WWTP) effluent. Expansion
      of WWTPs with advanced post-treatment processes, like effluent filtration, is
      widely proposed to meet possible future effluent discharge standards. When
      combining biological nitrate-nitrogen and chemical phosphorus removal in one
      filter, phosphorus limitation in the denitrifying process may occur. This study
      investigated where in the filter bed and under which conditions phosphorus
      limitation occurs. Profile measurements for nitrate, nitrite, and orthophosphorus
      (PO4-P) combined with chemical oxygen demand (COD) and 02 were conducted. Results
      showed that the required PO4-P/NOx-N ratio is approximately 0.006 mg/mg after
      phosphorous precipitation and flocculation. Profile measurements have proven to
      be an applicable and useful tool. It showed how nitrate and orthophosphorus are
      removed through the filter bed based on the PO4-P/NOx-N ratio. When
      orthophosphorus is removed more rapidly and efficiently compared to nitrate, the
      PO4-P/NOx-N ratio decreases. When PO4-P/NOx-N ratio thresholds are approximately
      0.006 mg/mg for a certain period of time and water temperatures varied
      significantly, orthophosphorus limitation may occur. Changing the filter-bed
      configuration or decreasing the coagulant dosage can prevent limitation of the
      denitrifying process because of a phosphorous shortage.

PMID- 22368825
TI  - Overcoming challenges to struvite recovery from anaerobically digested dairy
      manure.
AB  - Recovering struvite from dairy manure has consistently posed problems for
      researchers. This study separated solids from anaerobically digested dairy manure
      using a filtration system. Filtrate was rich in free magnesium (160 to 423 mg/L),
      ammonium (320 to 1800 mg N/L) and orthophosphate (93 to 332 mg P/L). High
      concentrations of free calcium (128 to 361 mg/L) and alkalinity (3309 to 6567
      mg/L as CaCO3), however, may hinder struvite precipitation. Batch precipitation
      tests were conducted to identify and overcome factors that interfere with
      struvite formation. Precipitation tests at pH 9 identified calcium and ionic
      strength as most probable interferences. Calcium addition did not significantly
      change phosphorus removal efficiency, but decreased struvite purity because of
      formation of calcium phosphates when Ca:P activity ratio was greater than 0.5 to
      1. Batch tests demonstrated effective calcium removal from anaerobically digested
      dairy manure through precipitation of calcium carbonate at pH 9 to 10 while
      retaining magnesium and orthophosphate, lessening hindrance to struvite
      formation.

PMID- 22368826
TI  - Toward long solids retention time of activated sludge processes: benefits in
      energy saving, effluent quality, and stability.
AB  - The activated sludge process is the most common method of secondary municipal
      wastewater treatment; solids retention time (SRT) is the key control parameter
      for this process. Typically, operating at long SRT is considered only for
      nitrification, but there are additional benefits of high SRT operation. This
      paper presents experimental and literature evidence to demonstrate three major
      additional benefits of long SRT operation: increased oxygen transfer efficiency;
      improved biomass particle size distribution, which results in more efficient
      clarification with fewer effluent particles and suspended solids; and enhanced
      removal of many emerging contaminants such as pharmaceuticals, personal care
      products, and endocrine disrupting compounds. This paper presents experimental
      results from several treatment plants that showed increasing oxygen transfer
      efficiency and particle size with increasing SRT, and evidence documenting
      improved removal of emerging contaminants and biodegradable organic carbon. A
      long-term survey of three treatment plants concludes that operating at higher SRT
      is not as energy intensive as typically assumed.

PMID- 22368827
TI  - Cotton-textile wastewater management: investigating different treatment methods.
AB  - The cotton-textile industry consumes significant amounts of water during
      manufacturing, creating high volumes of wastewater needing treatment. The organic
      load concentration of cotton-textile wastewater is equivalent to a medium
      strength municipal wastewater; the color of the water, however, remains a
      significant environmental issue. This research, in cooperation with a cotton
      textile manufacturer, investigated different treatment methods and different
      combinations of methods to identify the most cost-effective approaches to
      treating textile wastewater. Although activated-sludge is economical, it can only
      be used as part of an integrated wastewater management system because it cannot
      decolorize wastewater. Coagulation/flocculation methods are able to decolorize
      cotton-wastewater; however, this process creates high amounts of wastewater
      solids, thus significantly increasing total treatment costs. Chemical oxidation
      is an environmentally friendly technique that can only be used as a polishing
      step because of high operating costs. Anaerobic digestion in a series of fixed
      bed bioreactors with immobilized methanogens using acetic acid as a substrate and
      a pH-control agent followed by activated-sludge treatment was found to be the
      most cost-effective and environmentally safe cotton-textile wastewater management
      approach investigated.

PMID- 22368828
TI  - Delivery and frequency distributions of combined wastewater collection system wet
      and dry weather loads.
AB  - Combined wastewater collection systems continue to serve as a common urban
      conveyance method in urban areas of Europe and older urban areas of the United
      States. This study uses combined wastewater collection system monitoring data
      from the urbanizing Liguori catchment and channel in Cosenza (Italy) to
      illustrate event-based delivery and distribution of conveyed pollutant indices.
      Motivated by recent European Union (EU) discharge control legislation, this study
      specifically differentiates the event-based delivery of these indices between dry
      and wet-weather flows. Although the relatively steady to diurnal-variable
      delivery phenomena in dry weather flows are known, transport limiting phenomena
      for wet-weather hydrology and mass delivery typically are not known for the same
      catchment. Limiting categories of transport for a pollutant phase are generated
      by variables such as flow volume and duration, stream power, hydrograph
      parameters, and previous dry hours (PDH). Transport limitations of wet and dry
      weather events from the 414-ha catchment were analyzed and characterized as
      limited by mass indices (first-order, first flush transport) or limited by flow
      (zero-order transport). Results indicated significant concentration differences
      between mass- and flow-limited events. Higher concentrations were associated with
      mass-limited events. Frequency distributions of flow, total suspended solids
      (TSS), chemical oxygen demand (COD), and five-day biochemical oxygen demand
      (BOD5) were consistently exponential for wet-weather and mass-limited events. In
      contrast, flow, TSS, and BOD5 concentrations were distributed normally for flow
      limited events. Results indicated a reasonable linear relationship between
      discharged TSS, COD, and BOD5 (biochemical oxygen demand) for Liguori Channel
      discharges into the Crati River. Wet-weather event transport was predominately
      mass-limited for TSS, COD, and BOD5.

PMID- 22368829
TI  - Of: Hydraulic response and nitrogen retention in bioretention mesocosms with
      regulated outlets: part I--hydraulic response, W. C. Lucas, M. Greenway, 83, 692
      702 (2011).

PMID- 22368830
TI  - Of: Hydraulic response and nitrogen retention in bioretention mesocosms with
      regulated outlets: part II--nitrogen retention, W. C. Lucas, M. Greenway, 83, 703
      713 (2011).

PMID- 22368831
TI  - [Mouth diseases included in a world wide policy against non-communicable
      afflictions].

PMID- 22368832
TI  - [Odontogenic pain].

PMID- 22368833
TI  - [A solo practice is old fashion].

PMID- 22368834
TI  - [A solo practice is old fashion].

PMID- 22368835
TI  - [Long-term goals for oral health].
AB  - The current, optimistic prognosis is that newborns will reach an average age of
      100 years. This increased life-expectancy requires a renewed vision of long-term
      goals for oral health. The starting-point could be a prospective end-point with
      minimal oral function which should be reached, for example, in the last years of
      one's life. The consequence is that adequate oral healthcare for the elderly
      starts in childhood. Choices such as the extraction of premolars for orthodontic
      reasons and the dental re-restoration cycle have a great negative impact on
      reaching this goal. The average sustainability of dental restorations or
      prosthetic constructions is commonly much shorter than the life-expectancy of a
      patient. If oral treatment is necessary, it is recommended to give priority to
      maintaining a minimally functional dentition up to an advanced age, instead
      offocusing on short- or medium-term goals.

PMID- 22368836
TI  - [Melanoma].

PMID- 22368837
TI  - [Squamous cell carcinoma].

PMID- 22368838
TI  - [A man from Africa with a swelling in the head and neck region].
AB  - A general dental practitioner can, in the daily practice, be confronted with a
      patient with a swelling in the head and neck region. For such swellings an
      extensive differential diagnosis exists. Often such a swelling is caused by one
      or more enlarged lymph nodes due to a bacterial or viral infection. If a swelling
      in the head and neck region has been present for some time--longer than 4 weeks-
      then there is a considerable chance, especially in adults, that it is the result
      of the metastasizing of a malignancy, such as a squamous cell carcinoma in the
      oral mucosa or another mucosal site in the head and neck region. In addition to
      lymph node swellings resulting from a malignancy, diseases are now more
      frequently encountered which were previously uncommon in the Netherlands, due in
      part to the growing number of people with a non-Western ethnic background.
      Tuberculosis is such a rare disease, which can in the first instance express
      itself in the form of a lymph node swelling in the head and neck region.

PMID- 22368839
TI  - [Sclerosis of lymfangiomas in the head and neck area: evaluation with the use of
      stereophotogrammetry].
AB  - Lymangiomas are congenital malformations of the lymphatic system. They can appear
      at any age and in any part of the body. In the head and neck area lymangiomas can
      give rise to functional as well as esthetic problems. Therapy consist of
      sclerosis, possibly followed by surgical excision. Stereophotogrammetry is a
      relatively new technique which, by means of superimposition of pre- and
      postoperative images, provides the possibility to quantify treatment results. In
      this paper 3 patients who underwent treatment of a lymphatic malformation and in
      whom treatment results were measured with stereophotogrammetry are discussed. The
      conclusion can be drawn that stereophotogrammetry is a promising technique for
      evaluation of treatment results of superficially localised lymphatic
      malformations that displace the skin in the head and neck area.

PMID- 22368840
TI  - [Risks associated with erosive beverages in secondary school canteens in the
      Netherlands].
AB  - The consumption of acidic beverages may cause dental erosion. The consumption of
      such beverages during school hours may contribute to the development of erosion.
      In order to study the extent to which children of secondary schools are exposed
      to potentially erosive beverages, 43 locations in 37 schools in the Netherlands
      were visited. In each school, all available types of beverages were registered
      and classified as non-erosive or potentially erosive. In addition, the number of
      students, type of school, opening times of the canteens and the number of vending
      machines were recorded. It was revealed that a wide variety of beverages is
      available in school canteens, of which a large number are potentially erosive
      (71.8 +/- 12.9%). The number of different products available, the number of
      different beverages available and the number of potentially erosive drinks all
      correlated with the number of students per school, but not with the type of
      education. The number of drinks available and the number of potentially erosive
      drinks correlated with the opening hours of the canteens and the number of
      vending machines.

PMID- 22368841
TI  - [Dissertations 25 years after date 31. Black-pigmented oral bacteria in human
      oral infections].
AB  - In 1986, oral microbiology, and especially the microbiology of periodontal
      infections, was of central importance. Interest in periodontology was growing
      rapidly and with it, interest in developments in microbiology and the immunology
      of infectious diseases of the periodontium. At national and international
      meetings discussions took place concerning the role of the newly discovered
      bacterial species Actinobacillus actinomycetemcomitans and the role of
      antibiotics in the treatment of severe periodontitis. Since the 1980s, much has
      changed in periodontology, not least of all as a result of a new specialism: oral
      implantology. With it, a new disease also came into existence: peri-implantitis.

PMID- 22368842
TI  - [Advancements of computer chemistry in separation of Chinese medicine].
AB  - Separating technique of Chinese medicine is not only a key technique in the field
      of Chinese medicine' s research and development, but also a significant step in
      the modernization of Chinese medicinal preparation. Computer chemistry can build
      model and look for the regulations from Chinese medicine system which is full of
      complicated data. This paper analyzed the applicability, key technology, basic
      mode and common algorithm of computer chemistry applied in the separation of
      Chinese medicine, introduced the mathematic mode and the setting methods of
      Extraction kinetics, investigated several problems which based on traditional
      Chinese medicine membrane procession, and forecasted the application prospect.

PMID- 22368843
TI  - [Mould and mycotoxin contamination of medicinal materials].
AB  - Medicinal materials may be contaminated with a broad variety of fungi, which are
      represented by Aspergillus spp, Penlicillium spp, Fusarium spp, Rhizopus spp,
      Mucor spp et al. This fact limits the utilization of medicinal materials,
      besides, medicinal materials may also be contaminated with mycotoxins produced by
      these fungi, and bring harm to human health. Several mycotoxins have been
      detected in medicinal materials, such as AFTs, OTA, FBs, et al. The contamination
      may originate from the conditions in which the medicinal plants are cultivated,
      stored and in the finished product manufacturing stages. Some methods have been
      used for detoxifcation and disinfection for medicinal materials, but they have
      limited effects. Taking into consideration the background situation, it is
      important for medicinal materials to be protected from contamination of fungi at
      every stage of production. The present study intends to give a review of
      contamination of medicinal materials by moulds and mycotoxins and discuss the
      factors influencing this situation, expecting to contribute to the knowledge for
      reducing the contamination.

PMID- 22368844
TI  - [Safety evaluation of realgar-and cinnabar-containing traditional Chinese
      medicine].
AB  - Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional
      Chinese medicines for thousands of years. Both arsenic and mercury are well-known
      for toxic effects and the safety of realgar-and cinnabar-containing traditional
      Chinese medicines is of concern. It is considered that any intentional use of
      known toxic metals in medicine is an unacceptable risk, while an opposing opinion
      presumes that realgar and cinnabar have clear pharmacological action with
      tolerable side effects. This review summarized the progress of toxicological
      study on realgar-and cinnbar-containing traditional Chinese medicines.

PMID- 22368845
TI  - [Correlation between expression level of functional genes and tanshinones'
      accumulation in Salvia miltiorrhiza from different areas].
AB  - OBJECTIVE: To study the relationship between functional gene expression in Salvia
      miltiorrhiza from different producing areas and active principles, which might
      provide scientific basis for the gene regulation of tanshinones. METHOD: The
      quantitative determination of cryptotanshinone and tanshinone II A was carried
      out by using HPLC method, expression level of 3 functional genes of SmAACT, SmCMK
      and SmIPPI were investigated by real-time PCR method. RESULT: The content of
      active principles together with expression level of SmAACT and SmCMK were higher
      in S. miltiorrhiza from genuine producing areas including Henan and Shanxi, but
      lower in samples from Beijing which was non-genuine producing area. CONCLUSION:
      Expression level of SmAACT and SmCMK had close relationships involving
      tanshinones' accumulation, but the SmIPPI gene had not.

PMID- 22368846
TI  - [Absorption and allocation of nitrogen, phosphorus, potassium in Prunella
      vulgaris and their relationship to dry matter accumulation].
AB  - OBJECTIVE: The accumulation of dry matter, nitrogen, phosphorus and potassium in
      Prunella vulgaris and their relationships under field condition were studied, in
      order to provide a basis for the rational fertilization. METHOD: Through the
      dynamic sampling of P. vulgaris in different growing stages, and the dry weight
      of plant, the amount of dry matter and the content of N, P and K within each
      organ of the plant were measured. RESULT: The dry weight of P. vulgaris linearly
      increased with the increase of nitrogen, phosphorus and potassium accumulation,
      there existed a significant correlation at whole growth period. The maximum stage
      accumulation rate of dry matter from mid-April to the beginning of May, reached
      63.71%. The amount of dry matter was mainly distribution in leaves from late
      March to mid-April. The distribution ratio in stem was the highest from beginning
      of May to late May. Until mid-June, the distribution ratio of dry matter in
      spicas was higher than that in other organs. The absorption amounts of N, P and K
      were lower before mid-April, and the nutrient element was concentrated in plant
      leaves. From late April to beginning of May, the N, P and K accumulation reached
      maximum of total absorptive capacity, which accounted for 72.35%, 59.82%, 87.41%,
      respectively, and the mineral elements were concentrated distribution of plant
      stems. When transferred to reproductive stage, both accumulation amount and
      distribution rate of nutrient elements in spicas increased rapidly, which reached
      the maximum until mid-June. From elongation stages to quaring period was the
      period of maximal accumulation of dry matter and showed the maximal efficiency of
      N, P and K nutrition. CONCLUSION: The time from elongation stages to quaring
      period is the most crucial period in the growth development stage of P. vulgaris,
      and should be paid more attention to the supply of mineral nutrition and moisture
      of plant to promote spicas formation and dry matter accumulation in this stage.
      The average N, P2O5 and K2O absorption amount per 100 kg dry matter of spicas
      were 1.62, 0.36, 2.88 kg respectively, and the ratio of N-P2O5,-K2O was 1 : 0.22:
      1.77.

PMID- 22368847
TI  - [Isolation and characteristic of SmbHLH1 gene in Salvia miltiorrhiza].
AB  - OBJECTIVE: A novel bHLH-like gene, designated SmbHLH1, was isolated from Salvia
      miltiorrhiza, in order to identify a bHLH gene in related to danshinone
      biosysnthesis. METHOD: SmbHLH1 was isolated by RT-PCR,and Semi-quantitative RT
      PCR was used to detect the gene expression level. RESULT: The full length of
      SmbHLH1 cDNA has an open reading frame of 999 bp. The deduced amino acid sequence
      of SmbHLH1 has 332 amino acid residues which forms a 36 kDa polypeptide with a
      calculated pI of 5.4. SmbHLH1 gene was expressed at high level in root, but low
      level in stem, leaf and flower of S. miltiorrhiza. The transcripts of SmbHLH1 was
      suppressed when the plants were treated with exogenous MeJA, Yeast + Ag+. The
      transcripts of SmbHLH1 constitutively accumulated in response to exogenous ABA
      and low concentration of salicylic acid. CONCLUSION: SmbHLH is a new member of
      the S. miltiorrhiza bHLH family, and its possible roles in brassinosteriods
      signaling responses.

PMID- 22368848
TI  - [Quality testing and quality classification standard establishment of Trollius
      chinensis seeds].
AB  - OBJECTIVE: To study quality test, and establish quality classification standard
      of Trollius chinensis. METHOD: Seed purity, weight per 1 000 seeds, seed moisture
      content, seed viability and their exterior parameters of the seed samples from
      different producing areas were measured, K cluster analysis was applied for the
      data analysis. RESULT AND CONCLUSION: Quality of T. chinensis seeds from
      different producing areas was analyzed, and the primary T. chinensis seed quality
      classification standard was established.

PMID- 22368849
TI  - [Genetic diversity analysis of Paris by RSAP makers].
AB  - OBJECTIVE: Studies on DNA fingerprinting of eight species of Paris and
      application of restriction site amplification polymorphism (RSAP) to the
      identification of Paris. METHOD: Sequence-related amplified polymorphism (SRAP)
      molecular markers were used to detect the genetic diversity of 7 accessions of
      Paris collected from Tianquan and Baoxing in Sichuan, and one from Lijiang in
      Yunnan. RESULT: The DNA fingerprinting of 8 species were generated by 18 primer
      combination screened from 45 primer combinations. Eight accessions were clustered
      into 4 groups by genetic distance. CONCLUSION: Based on molecular biology methods
      of RSAP analysis, accurate molecular identification could be performed on
      traditional Chinese medicinal material plants in Paris, and provided molecular
      evidence for taxonomy and identification of different species in Paris.

PMID- 22368850
TI  - [Studies on allelopathic effect of artemisinin on rhizobium].
AB  - Two strains of bean rhizobia, Rhizobium vigna 01 (slow-growing Rhizobium) and Rh.
      vigna 03 (fast-growing Rhizobium), were adopted to study allelopathic effect of
      artemisinin on the rhizobia. The results showed a significant inhibition of the
      reproduction and growth of rhizobium by artemisinin. After about 8 hours by
      adding 40 mg x L(-1) artemisinin into the culture medium, the number of rhizobia
      was less than half of those in normal culture. The utilization of sucrose and
      glucose by rhizobia decreased significantly as the concentration of artemisinin
      increased in the culture medium, which could be one of the main reasons for the
      inhibition of reproduction and growth of rhizobia by artemisinin. In addition,
      the activities of extracellular protease and acid phosphatase released from
      rhizobia decreased significantly as the concentrations of artemisinin increased.
      Artemisinin refluxed from Artemisia annua could thus inhibit the formation of
      root nodules and interfered with energy supply and reception between bacteroid
      and host cells. y = e(-ax) + b reflected the relationships between nitrogenase
      activities (y) and concentrations of artemisinin (x). In the culture medium with
      48 mg x L(-1) of artemisinin, nitrogenase activities were about zero, resulting
      in the inactivation of nitrogenase in nodules formed. In general, artemisin in A.
      annua grown soils may inhibit the reproduction and growth of rhizobia, nodule
      formation and nitrogen biofixation, leading to less nitrogen supply, poor growth
      and development, and low yields of beans.

PMID- 22368851
TI  - [Analysis of volatile oil in Gardenia jasminoids roasted with ginger juice by GC
      MS].
AB  - OBJECTIVE: To compare the components and contents of volatile oil in Gardenia
      jasminoids, Zingiber officinale, G. jasminoids roasted with ginger juice and to
      provide scientific basis for intrinsic material of G. jasminoids roasted with
      ginger juice. METHOD: The volatile oil in the three herbal medicines was
      extracted by steam distillation, the components were analyzed by GC-MS and the
      contents of the components were calculated by area normalization method. RESULT:
      The contents of volatile oil in G. jasminoids, Z. officinale, G. jasminoids
      roasted with ginger juice were 1.0, 2.0, 1.5 microL x g(-1), respectively. A
      total of 89 components were identified by GC-MS. Although 42, 75 and 77 peaks
      were separated, only 30, 58 and 67 components were identified accordingly, which
      accounted 94.1%, 90.52% and 94.38% of the whole volatile oil. CONCLUSION: After
      being processed with ginger juice, the components and contents of volatile oil in
      G. jasminoids has been changed obviously.

PMID- 22368852
TI  - [Multi-mathematical modelings for compatibility optimization of Jiangzhi
      granules].
AB  - OBJECTIVE: To investigate into the method of "multi activity index evaluation and
      combination optimized of mult-component" for Chinese herbal formulas. METHOD:
      According to the scheme of uniform experimental design, efficacy experiment,
      multi index evaluation, least absolute shrinkage, selection operator (LASSO)
      modeling, evolutionary optimization algorithm, validation experiment, we
      optimized the combination of Jiangzhi granules based on the activity indexes of
      blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio
      of liver tissue to body. RESULT: Analytic hierarchy process (AHP) combining with
      criteria importance through intercriteria correlation (CRITIC) for multi activity
      index evaluation was more reasonable and objective, it reflected the information
      of activity index's order and objective sample data. LASSO algorithm modeling
      could accurately reflect the relationship between different combination of
      Jiangzhi granule and the activity comprehensive indexes. The optimized
      combination of Jiangzhi granule showed better values of the activity
      comprehensive indexed than the original formula after the validation experiment.
      CONCLUSION: AHP combining with CRITIC can be used for multi activity index
      evaluation and LASSO algorithm, it is suitable for combination optimized of
      Chinese herbal formulas.

PMID- 22368853
TI  - [Study on industrialized production technology of fresh-cut for Paeonia radix
      alba].
AB  - OBJECTIVE: To optimize the objective technical parameter for direct processing
      technology of fresh-cut for Paeonia Radix Alba. METHOD: Peoniflorin and TGP were
      employed as the indexes of quality evaluation. Combining with the appearance of
      the slices, we investigated the influence of slice degree and thickness, drying
      temperature, drying time, drying method and other factors on the quality control
      of Paeonia Radix Alba slices. Furthermore, the key fresh-cut technology operating
      procedures parameter for Paeonia Radix Alba in Bozhou was established based on
      the semi-works production. RESULT: It established tentatively the method for
      fresh-out and fresh-out after boiled of Paeonia Radix Alba as that selected fresh
      or beiled Paeonia Radix Alba, then divided them from different grades and put
      them into a roller to crash off the skin, cleaned and then dried them 9 h at 60
      degrees C (water content 28% - 32%), and then moistened 2-3 h after spraying
      moderate water. Cut them into 1.5-2 mm decoction pieces and dried them at 60
      degrees C, cooled, and sealed them in a package. CONCLUSION: The
      industrialization of processing decoction pieces with freshly cut Paeonia Radix
      Alba is stable shortens processing time, avoids effectively sulfur fumigation and
      infiltrating and soften, and keep high quality of production.

PMID- 22368854
TI  - [Determination of six lignin components in crude and different processed products
      of Schisandra chinensis].
AB  - OBJECTIVE: To compare the contents of lignin in crude and processed fruits of
      Schisandrae chinensis, and to explore the processing mechanism of S. chinensis
      fruits. METHOD: Contents of schisandrin, schisandrol B, deoxyschisandrin, gomisin
      N, gamma-schizandrin and schisandrin C were determined by high performance liquid
      chromatography (HPLC). RESULT: Except the content of Schisandrol B was higher or
      less in processed fruits than that in the crude, the other lignin contents of S.
      chinensis fruits in different processed products were higher than that in the
      crude. The alcohol-processed product had the highest content of lignin.
      CONCLUSION: The contents of lignin have changed by different processed methods,
      and alcohol-processed method may be the best processed method.

PMID- 22368855
TI  - [Furosteroidal saponin from Smilacina japonica].
AB  - Smilacina japonica is a perennial herb, belonging to Smilacina genus of
      Liliaceae. A new furosteroidal saponin (1) was isolated and purified from the
      ethanol extract of the rhizome of S. japonica by various column chromatography.
      Its structure was established as 26-O-beta-D-glucopyranosyl-(25R)-furost-5-en
      3beta, 12, 17alpha, 22xi, 26-pentol-12-O-acetyle-3-O-alpha-L-rhamnopyranosyl-(1 -
      > 2)-beta-D-glucopyranoside by physical and chemical properties and IR, MS, 1D,
      2D NMR techniques. It showed strong cytotoxicity against the SPC-A-1 cancer cell
      lines.

PMID- 22368856
TI  - [Studies on chemical constitutes from callus cultures of Stellera chamaejasme].
AB  - From callus cultures of Stellera chamaejasme, 17 compounds were isolated. Based
      on their physical and chemical data and spectroscopic analysis, they were
      identified as syringaresinol (1), medioresinol (2), pinoresinol (3), (1R, 2S, 5R,
      6S)- 2-(4- hydroxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3, 7-dioxabicyclo [3, 3,
      0] octane (4), epipinoresinol (5), caruilignan D (6), 3-oxo-guai-4-ene-11, 12
      diol (7), (-) -lariciresinol (8), tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4
      hydroxyphenyl) methyl]-3-furanmethanol (9), 5'-methoxylariciresinol (10),
      vladinol D (11), cyclo (L-Pro-L-Val) (12), oxomatairesinol (13), (+) -guayarol
      (14); acutissimalignan B (15), isolariciresinol (16), and beta-sitosterol (17),
      respectively. Among these compounds, 12 was a cyclodipeptide, 7 was a
      sesquiterpene, and the others except 17 were lignans. All compounds were first
      isolated from callus cultures of S. chamaejasme.

PMID- 22368857
TI  - [Study on chemical constituents of rhizome of Ardisia gigantifolia].
AB  - OBJECTIVE: To study the chemical constituents of the dried rhizome of Ardisia
      gigantifolia. METHOD: The 60% ethanol extract was extracted with EtOAc, and then
      separated and purified by column chromatography using silica gel and preparative
      HPLC. Their structures were identified on the basis of spectral analysis and
      physico-chemical properties. RESULT: Nine compounds were isolated and identified
      as 11-O-galloylbergenin (1), 11-O-syringylbergenin (2), 11-O
      protocatechuoylbergenin (3), 4-O-galloylbergenin (4), 11 -O-vanilloylbergenin
      (5), (-) -epicatechin-3-gallate (6), stigmasterol-3-O-beta-D-glucopyranoside (7),
      (-) -4'-hydroxy-3-methoxyphenyl-beta-D-[6-O-(4"-hydroxy-3", 5"-dimethoxybenzoyl)]
      -glucopyranoside (8), and beta-sitosterol (9). CONCLUSION: Compounds 3, 4 and 7
      were isolsted from the genus Ardisia for the first time, while compounds 1, 2, 5
      and 6 were isolated from this plant for the first time.

PMID- 22368858
TI  - [Analysis of gingerol-related compounds in fresh ginger by HPLC-ESI-Q-TOF-MS/MS].
AB  - To establish a rapid method for analysis of gingerol-related compounds in fresh
      ginger by using high performance liquid chromatography coupled with electron
      spray ionization-quadrupole-time of flight mass/mass spectrometry (HPLC-ESI-Q-TOF
      MS/ MS). The gingerol-related compounds in fresh ginger was separated by an
      Inertsil ODS-SP column (4.6 mm x 250 mm, 5 microm) using a binary eluent under
      gradient conditions. The analytes were detected by ESI-Q-TOF-MS/MS in positive
      ion mode to obtain MS and MS/MS spectra and to extract molecular weights. From
      the MS data, the accurate molecular weights of gingerol-related compounds were
      obtained, and from the MS/MS data, the (+) ESI-Q-TOF-MS/MS fragments were
      obtained. 25 gingerol-related compounds were identified from fresh ginger by
      attentive studying on the mass spectra of compounds and comparing with reference
      data reported in the literature, respectively. This method was certified to be
      accurate and reliable and can be used for the rapid analysis of gingerol-related
      compounds in fresh ginger.

PMID- 22368859
TI  - [Determination of loganin in Pterocephalus hookeri by HPLC].
AB  - OBJECTIVE: To develop an HPLC method for determination of loganin in
      Pterocephalus hookeri. METHOD: The analysis was performed on a Welchrom C18
      column (4.6 mm x 250 mm, 5 microm) with acetonitrile-water (12:88) as the the
      mobile phase at a flow rate of 1 mL x min(-1) and the detection wavelength was
      240 nm. RESULT: The peak areas and injection amounts of loganin had a good linear
      relationship at the range of 0.06-1.2 microg. The average recovery was 97.0%, and
      the RSD was 1.4%. CONCLUSION: The method is simple, accurate, and can be used for
      its quality control.

PMID- 22368860
TI  - [Study on fingerprint chromatograms of extract of cimicifugae rhizoma].
AB  - OBJECTIVE: To establish the fingerprint chromatograms of the extract of
      Cimicifugae Rhizoma firstly. METHOD: Phenolic acids and triterpenoid saponins
      were analyzed by HPLC. Hypersil BDS C18 (4.6 mm x 250 mm, 5 microm) column was
      used, the mobile phase was composed of acetonitrile -0.1% H3PO4 with gradient
      elution, flow rate was 1.0 mL x min(-1), column temprature was 30 degrees C, and
      the detection wavelength was set at 316 nm and 210 nm. RESULT: In the fingerprint
      of phenolic acids, thirteen feature peaks were found and the RSD of relative
      retention time and relative peak area were all less than 3% in the precision and
      repeation experiments. The similarity of ten batches of samples were all more
      than 0.90. In the fingerprint of triterpenoid saponins, fourteen feature peaks
      were found and the RSD of relative retention time and relative peak area were all
      less than 4% in the precision and repeation experiments. The similarity of ten
      batches of samples were all more than 0.90. CONCLUSION: This method is
      comprehensive, stable, reliable and can be used to evaluate the quality of the
      extract of Cimicifugae Rhizoma. It has provided a reference to the analysis on
      pharmacodynamic deferences of Cimicifuga extracts and also laid the foundation
      for its further development.

PMID- 22368861
TI  - [GC-MS analysis on volatile components of wild Trogopterus faeces from Laishui
      county of Hebei province].
AB  - OBJECTIVE: To analysis the volatile components of Trogopterus faeces. METHOD: The
      volatile components of Trogopterus faeces was extracted by steam distillation and
      analyzed by GC-MS. RESULT: Eighty-five volatile components were identified and
      the main components are cedrol (12.31%) and caryophyllene (7.5%). CONCLUSION: The
      volatile components of the samples are originated from the ingredients or other
      chemical compositions with similar basic structure of the fodders.

PMID- 22368862
TI  - [Regulation of sishen wan on Bax/Bcl-2 mRNA, Fas/FasL in colonic tissue from rats
      with colitis].
AB  - OBJECTIVE: To evaluate therapeutic effect of Sishen Wan on experimental colitis,
      and explore its mechanism by expression of Bax/Bcl-2 mRNA, Fas/FasL in colonic
      tissue. METHOD: Experimental colitis was induced by rectal administration of
      trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol. The model animals were
      divided into four groups: the induced colitis but untreated group, the induced
      colitis groups treated with the high, middle, low dose of Sishen Wan, and the
      induced colitis group treated with salicylazosulfapyridine (SASP). After 10 day
      administration, the body weight, colonic wet weight, colonic weight index,
      colonic damage score and pathological change were evaluated, and the level of Fas
      and FasL by flow cytometry, Bax mRNA and Bcl-2 mRNA by reverse transcription
      polymerase chain reaction (RT-PCT). RESULT: Compared with the model group, the
      colonic wet weight and colonic weight index were remarkably decreased in the
      middle dose of Sishen Wan group (P < 0.05). The colonic injury scores were
      significantly reduced after rats were treated with the three doses of Sishen Wan
      (P < 0.05). Representative restored features were observed including fewer
      inflammatory cellular infiltration and follicular hyperplasia, superficial and
      little ulcer with fibroplasia in colonic mucosa from the treated groups. The
      expression of Fas in the colonic mucosa was obviously down-regulated (P < 0.05)
      and the ratio of Bcl-2 mRNA/Bax mRNA was significantly up-regulated (P < 0.05) in
      the groups treated with the three doses of Sishen Wan. CONCLUSION: Sishen Wan
      might postpone colonic epithelium apoptosis or improve inflammatory cell
      apoptosis by regulating the expression of Fas/ FasL and Bax/Bcl-2 mRNA in colonic
      tissue, which is possible potential path to effectively treat experimental
      colitis by enema.

PMID- 22368863
TI  - [Study on characteristics of energy metabolism in skeletal muscle of rats with
      postoperative fatigue syndrome and interventional effect of ginsenoside Rb1].
AB  - OBJECTIVE: To study characteristics of energy metabolism in the skeletal muscle
      of rats with postoperative fatigue syndrome (POFS) and the interventional effect
      of ginsenoside Rb1. METHOD: We chose resection of 70% of the "middle" small
      intestine as the rat model for POFS. Ninety-six adult male SPF SD rats were
      randomly divided into the control group, the model group, and the ginsenoside Rb1
      treated group by body weight. And then, each group was further randomly divided
      into four subgroups, according to different postoperative investigated time
      points, such as postoperative day 1, postoperative day 3, postoperative day 7 and
      postoperative day 10. So the animals were divided into twelve subgroups (n = 8 in
      each subgroup). Rats of the control group and the model group were injected
      intraperitoneally with saline at the dose of 10 mL x kg(-1) one hour before the
      operation and once a day during the postoperative days. Rats of the ginsenoside
      Rb1-treated group were administered 10 mg x kg(-1) ginsenoside Rb1 by the same
      method. The skeletal muscles were sampled on postoperative day 1, 3, 7 and 10.
      The contents of ATP, ADP, AMP in skeletal muscles were determined by HPLC, and
      the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase were investigated by
      colorimetry. RESULT: Compared with the control group, the content of ATP in
      skeletal muscle of rats of the model group decreased significantly on
      postoperative day 3 (P < 0.05), while the content of ADP significantly increased
      on postoperative day 7 and 10 (P < 0.05). The activity of Na(+)-K(+)-AT-Pase
      decreased on postoperative day 3 and 7 (P < 0.05), and the activity of Ca(2+)
      ATPase decreased on postoperative day 7. After supplement of ginsenoside Rb1, on
      the investigated time points, all the negative changes of the indicators
      discovered above were significantly adjusted (P < 0.05) in rats of the
      ginsenoside Rb1-treated group, while no significant differences were
      investigated. CONCLUSION: During a certain period of postoperative time, the
      activity of energy metabolism is depressed in the skeletal muscle of rats with
      POFS, but it can be improved by supplement of ginsenoside Rb1.

PMID- 22368864
TI  - [Effect of berberine on expression of transforming growth factor-beta1 and type
      IV collagen proteins in mesangial cells of diabetic rats with nephropathy].
AB  - OBJECTIVE: To explore the effect and mechanism of berberine on diabetic
      nephropathy in experimental rats. METHOD: The rat model of diabetic nephropathy
      was induced by injection of streptozocin (STZ). The rats were divided into 6
      groups: control group, model group, 3 berberine treatment groups and Xiaoke Wan
      (XKW) treatment group. The fasting blood glucose (FBG), kidney weight/body weight
      (KW/BW), blood urea nitrogen (BUN), creatinine (Cr) and urinary protein (Upro)
      were tested 8 weeks later. The expression of transforming growth factor-beta1
      (TGF-beta1) and type IV collagen (IV-C) proteins in renal tissue of diabetic rats
      with nephropathy were observed by optical micrography. RESULT: Berberine could
      reduce the levels of FBG, KW/BW, BUN, Cr, Upro and the expression of TGF-beta1
      and IV-C proteins in renal tissue of diabetic rats with nephropathy. CONCLUSION:
      Berberine may protect renal function and slow down the progression of diabetic
      nephropathy in rats by suppressing the expression of TGF-beta1 and IV-C proteins
      in renal tissue.

PMID- 22368865
TI  - [Effects of jingqianshu granule on expression of 5-HT(1A)R of PMS model rats with
      liver-qi stagnation].
AB  - OBJECTIVE: To research the effect of the Jingqianshu granule (JQS) on the
      expression of serotonin receptor-1A (5-HT(1A)R) in hippocampus and hypothalamus
      of premenstrual syndrome (PMS) model rats with Liver-qi depression. METHOD: The
      PMS model rats with Liver-qi depression were induced by bandaging the limbs. The
      model rats were treated with JQS, and evaluated by open-field test. The
      expression of 5-HT(1A)R in hippocampus and hypothalamus was analysed by the
      method of RT-PCR and Western blot. RESULT: After the JQS were administered, the
      open field scores, the expression of 5-HT(1A)R mRNA and protein in hippocampus
      and hypothalamus of rats increased significantly. CONCLUSION: The JQS granule can
      up-regulate the expression of 5-HT(1A)R in hippocampus and hypothalamus, which
      maybe one of the mechanism to treat PMS with liver-qi depression.

PMID- 22368866
TI  - [Effects and mechanisms of total flavonoids of astragali radix and calycosin on
      inhibiting human erythroleukemia cell line K562].
AB  - OBJECTIVE: To investigate the effects of total flavonoids of Astragali Radix
      (TFA) and calycosin on apoptosis induction and cell cycle in human
      erythroleukemia cell line K562. METHOD: MTT assay was used to measure the
      inhibition effect on the proliferation of K562 cells cultured with TFA and
      calycosin. The effect of TFA and calycosin on cell cycle in K562 was detected by
      PI staining. The apoptosis induction effect was measured by Annexin V/PI double
      staining. RT-PCR was used to determine the level of Cyclin D1 mRNA in K562 cells
      after treated with TFA and calycosin. RESULT: TFA and calycosin could inhibit the
      proliferation of K562 cells, the 50% inhibiting concentration of TFA and
      calycosin were 98.63 mg x L(-1) and 130.32 mg x L(-1) respectively. TFA and
      calycosin could not induce apoptosis in K562 cells, but could increase the number
      of cells in the G0/G1 phase. The level of Cyclin D1 mRNA in K562 cells decreased
      after treated with TFA and calycosin. CONCLUSION: TFA could inhibit the
      proliferation of K562 cells, and attribute to arrest them in the G0/G1 phase and
      decrease Cyclin D1 mRNA.

PMID- 22368867
TI  - [Primary research on daily administration times of rhubarb used to treat
      experimental jaundice in rats].
AB  - OBJECTIVE: To study the rational daily administration times of rhubarb when it is
      used to treat experimental jaundice in rats, at the same time, validate the
      accuracy and feasibility of the method which was previously established to
      research the rational daily administration times of rhubarb (PD-PK method), and
      consummate it. METHOD: After the rats were modeled by 4% ANIT (75 mg x kg(-1))
      for two days, rhubarb extraction was drenched 3.6 g x kg(-1) once a day, 1.8 g x
      kg(-1) twice a day and 1.2 g x kg(-1) three times a day, respectively. Then the
      total bile and the flow rate of bile were observed. Blood was collected from the
      veins behind the eye sockets after different intervals and was used to
      investigate the biochemical indexes of the blood serum, such as TBIL, ALT, ALP,
      AST and GGT, and to determine the concentration of rheic acid in the blood
      plasma, then the time-effect curve and time-dose curve were obtained. The
      rational daily administration times of rhubarb was determined when it was used to
      treat experimental jaundice based on the comprehend analysis of time-effect and
      time-concentration relationships. RESULT: Compared with the groups which were
      administered once a day and three times a day, the total bile within 8 h of the
      rats which were administered twice a day was 1.56 and 1.7 times higher,
      respectively, while the TBIL was 23%, 22%, and ALT was 86%, 65% of the other two,
      ALP was 50%, 71% of the other two, respectively. With administrated twice a day,
      the blood concentration of rheic acid could maintain a high level for a longer
      time, which maybe the main reason for its effect. CONCLUSION: The method based on
      pharmacodynamics and pharmacokinetics is scientific and feasible to study the
      rational daily administration times of traditional Chinese medicine. Rhubarb is
      better to administrate two times a day to treat jaundice.

PMID- 22368868
TI  - [Correlation between antimetastatic action of Ajuga decumbens and expression of
      MMPs and TIMPs].
AB  - OBJECTIVE: To investigate the anticancer and anti-metastatic effect of Ajuga
      decumbens extraction (HBG) on breast cancer and to clarify the effect of HBG on
      MMPs and TIMPs. METHOD: The antitumor and antimetastic effect of HBG was
      determined using orthotopic 4T1 breast cancer mouse model. Western blot analysis
      was employed to detect the expression of associated proteins in breast cancer
      metastasis. RESULT: Administration with 50-200 mg x kg(-1) doses of HBG
      significantly reduced the tumor weight, tumor volume and numbers of lung tumor
      nodules in a dose-dependent manner. Tumor metastasis correlated proteins were
      altered following HBG treatment, MMP-2 and MMP-9 were down-regulated while TIMP-1
      and TIMP-2 were up-regulated. CONCLUSION: HBG showed anticancer and
      antimetastatic effect towards breast cancer through regulating the expression of
      MMPs and TIMPs. These data sustain our contention that HBG might be used as a
      potential therapeutic agent.

PMID- 22368869
TI  - [Study on pharmacokinetics of oridonin in mice].
AB  - OBJECTIVE: To develop a HPLC method for the determination of plasma concentration
      of oridonin (ORI) and study the pharmacokinetics of ORI in mice. METHOD: Blood
      was sampled from mice which were injected ORI by 10 mg x kg(-1) at different time
      intervals, and the concentration of ORI was determined by HPLC. The
      pharmacokinetic parameters were accessed by 3P97. RESULT: The calibration curve
      was linear (r = 0.998 7) within the range of 0.202-20.0 mg x L(-1) for ORI in
      plasma. The average recoveries were more than 93%. The within-day and between-day
      precisions were no more than 9%. After i.v. oridonin in mice, the plasma
      concentration-time course fitted well to two-compartment model. The
      pharmacokinetic equation was C = 16.192 5e(-0.554 6t) + 5.475 7e(-0.016 3t). The
      pharmacokinetic parameters were below: t1/2alpha 1.249 9 min, t1/2beta 42.638 4
      min, K21 0.152 3 min(-1), K12 0.359 3 min(-1), K10 0.0592 min(-1), AUC 366.035 0
      microg x min x mL(-1), CL 0.0273 L x min(-1) x kg(-1), V(c)0.461 5 L x kg(-1).
      CONCLUSION: The method can be used to determine the concentration and to
      investigate the pharmacokinetics of ORI in mice. ORI was absorbed and distributed
      very fast in mice. The effect of ORI was rapid. The elimination was the main
      process.

PMID- 22368870
TI  - [Studies on pharmacokinetics of evodiamine and rutaecarpine in rats plasma after
      oral administration extracts of euodiae fructus].
AB  - OBJECTIVE: Develop an LC-MS method to determine evodiamine and rutaecarpine in
      rats plasma simultaneously. The method was employed to investigate
      pharmacokinetics of evodiamine and rutaecarpine. METHOD: Blood samples were
      collected in different time after oral administrated with the extracts of Euodiae
      Fructus, the plasma concentration of evodiamine and rutaecarpine was determined
      by LC-MS, pharmacokinetic parameters were calculated by WinNonlin 5.1 software.
      RESULT: The linear ranges of evodiamine and rutaecarpine were 0.5-100 microg x L(
      1) (r = 0.995 9), 1-200 microg x L(-1) (r = 0.999 3) respectively. The average
      recovery were exceeded 76% (n = 5), the precision of inner-day and inter-day were
      less than 15%. The pharmacokinetics parameters AUC, t1/2, CL _F of evodiamine
      were: (2 215.24 +/- 414.49), (4 230.62 +/- 753.77), (13 219.21 +/- 3 740.95) min
      x ng(-1) x mL(-1); (146.57 +/- 38.38), (114.38 +/- 14.65), (163.37 +/- 8.83) min;
      (184 607.29 +/- 32 502.21), (192 878.22 +/- 31 897.37), (19 3224.63 +/- 62
      278.74) mL x min(-1). The pharmacokinetics parameters AUC, t1/2, CL_F of
      rutaecarpine were (2 283.53 +/- 298.51), (4 424.84 +/- 276.95), (14 239.93 +/-
      3648.27) min x ng(-1) x mL(-1); (167.10 +/- 15.82), (131.58 +/- 20.07), (144.41
      +/- 13.65) min; (1 177 340.54 +/- 2 4942.21), (181 262.92 +/- 11 162.22), (177
      508.10 +/- 52 611.80) mL x min(-1). CONCLUSION: The method described in this
      report has high sensitivity and selectivity, and was suitable for pharmacokinetic
      studies of evodiamine and rutaecarpine. The kinetic process of evodiamine and
      rutaecarpine in rats in vivo were all yielded to be one-compartment model.

PMID- 22368871
TI  - [Studies on intestinal absorption of alkaloids in Coptis chinensis by in situ
      single-pass perfused rat intestinal model].
AB  - OBJECTIVE: To study the absorption characteristics of alkaloids in Coptis
      chinensis in rat intestinal. METHOD: In situ single-pass perfused rat intestinal
      model was used and the concentrations of berberine and palmatine were determined
      by HPLC, the drug absorption rate constant (K(a)) and apparent absorption
      coefficient (P(app)) were tested to evaluate their absorption characteristics.
      RESULT: The absorption of berberine and palmatine in different regions of rat
      intestinals was significantly different. From bigness to smallness, the P(app)
      value of berberine at 50 mg x L(-1) were ileum, duodenum, jejunum and colon, of
      palmatine at 50 mg x L(-1) were ileum, colon, jejunum and duodenum. The
      concentration of berberine and palmatine had distinctive effect on the K(a) value
      of berberine and palmatine were ordered from larger to little as in Wujiwan
      compatibility, Coptis chinensis extractive and single compound. CONCLUSION: The
      berberine and palmatine were absroped at all regions of rat intestinal. The
      absorption characteristics of 2 alkaloids were not passive diffusion. The other
      ingredients in Wujiwan compatibility and Coptis chinensis extractive could
      promote the absorption of alkaloids.

PMID- 22368872
TI  - [Effects of polydatin on bleomycin-induced pulmonary fibrosis in rats].
AB  - OBJECTIVE: To observe the effects of three different doses of polydatin (PD) on
      pulmonary interstitial fibrosis in rats induced by bleomycin. METHOD: One hundred
      and twenty-nine healthy Sprague-Dawley rats three months old, were randomly
      divided into six groups. Group A: normal control group; group B: model group
      treated with bleomycin (pretreatment with saline 1 mL x kg(-1) intraperitoneally
      before bleomycin); group C: PD 10 mg x kg(-1) (pretreatment with PD 10 mg x kg(
      1) intraperitoneally before bleomycin); group D: PD 20 mg x kg(-1) (pretreatment
      with PD 20 mg x kg(-1) intraperitoneally before bleomycin); group E: PD 40 mg x
      kg(-1) (pretreatment with PD 40 mg x kg(-1) intraperitoneally before bleomycin),
      group F: dexamethason (DXM) treated group (pretreatment with saline 1 mL x kg(-1)
      intraperitoneally before bleomycin and then with DXM 1 mg x kg(-1) x d(-1)). At
      day 3, 7, 14, 28 after injection of bleomycin, eight rats in each group were
      randomly chosen to be killed. The right lungs of dead rats were removed and
      appropriately processed for hematoxylin and eosin (H&E) stain, histologically
      observed under light microscope. The hydroxyproline content and the PLA2 activity
      in pulmonary homogenate were measured with alkaline hydrolysis assay and acid
      modified microtitrimetic method. The levels of leukotriene C4 (LTC4),
      prostaglandin E2 (PGE2), transforming growth factor-beta1 (TGF-beta1) in
      bronchoalveolar lavage fluid (BALF) were measured with enzyme-linked
      immunosorbent assay (ELISA). RESULT: At day 3, 7, 14, 28 after intratracheal
      instillation of bleomycin in rats of group B, the PLA2 activity in lung
      homogenate and the levels of its metabolic products PGE2, LTC4 as well as TGF
      beta1 in BALF increased significantly compared with those in group A (P < 0.01).
      And lung hydroxyproline concentration began to grow up markedly at day 7 compared
      with those in group A (P < 0.05), reaching its maximum at day 28. Compared with
      group B, three different doses of PD and DXM significantly reduced the activity
      of the PLA2 and hydroxyproline concentration in lung homogenate as well as the
      levels of PGE2, LTC4, TGF-beta1 in BALF at various periods (P < 0.05). There was
      statistically significant difference between three different doses of PD groups
      (P < 0.05). And the group E (PD 40 mg x kg(-1)) was lower than group D (PD 20 mg
      x kg(-1)), group D was lower than group C (PD 10 mg x kg(-1)) (respectively, P <
      0.01). Group E and DXM group were no significant difference. However, all these
      observation parameters were higher than the normal level (compared with group A,
      P < 0.01). Histological studies revealed that it was showed less inflammation and
      a lower degree of fibrosis in the lungs treated with PD than bleomycin model
      group. CONCLUSION: PD has the protective effect on pulmonary interstitial
      fibrosis. However, it can't completely block the process of pulmonary fibrosis.

PMID- 22368873
TI  - [Effects of pseudolaric acid B on apoptosis of bladder cancer cell 5637].
AB  - OBJECTIVE: To investigate the apoptosis of bladder cancer cell 5637 induced by
      pseudolaric acid B in vitro and its mechanism. METHOD: The cell proliferation was
      detected by MTT assay;the cell cycle was measured by flow cytometry; the cell
      apoptosis was observed by flow cytometry with Annexin V-FITC/PI double staining;
      the expressions of survivin protein and caspase-3 protein were detected by
      Western blot assay. RESULT: It showed that pseudolaric acid B remarkably induced
      apoptosis of 5637 cell line. Moreover, pseudolaric acid B suppressed survivin and
      up-regulated caspase-3 expression. CONCLUSION: Pseudolaric acid B inhibits the
      proliferation and induces the apoptosis of 5637 cells. The molecular mechanism of
      pseudolaric acid B inducing the apoptosis of 5637 cells may be associated with
      its action of down-regulating the expression of survivin, and up-regulating the
      expression of caspase-3.

PMID- 22368874
TI  - [Reduning injection for community-acquired pneumonia: meta-analysis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Reduning injection for treating
      community-acquired pneumonia. METHOD: Literatures about randomized controlled
      trials of Reduning injection for treating community-acquired pneumonia were
      reviewed. The methodological quality of the trials was assessed by the Jadad
      scale, and evaluation was performed. RESULT: Seven RCTS were included. Reduning
      combined group (Reduning injection plus antibiotics and basic therapy) was
      compared with antibiotics group (antibiotics plus basic therapy). Meta-analysis
      showed that the relative risk (RR) for the total cure rate was 1.34, and 95%
      confidence interval (CI) was [1.19, 1.51]; RR for the total effective rate was
      1.10, and 95% CI was [1.06, 1.15]. The weighted mean difference (WMD) in
      disappearance time of fever between the two groups was - 1.42, and 95% CI was [-
      2.58, -0.26]; The WMD between the two groups for the total obvious effect rate of
      cough and expectoration were - 2.36, and 95% CI was [- 3.41, - 1.31]; Improve the
      time of pulmonary rales MD -2.30, 95% CI [- 2.61, - 2.00]; The WMD between the
      two groups in absorption of chest x-ray shadow was -2.36 and 95% CI [-2.52, 
      2.20]. Serious systematic adverse reactions had not been reported in the trials.
      CONCLUSION: The effect of combined therapy with Reduning injection plus
      antibiotics and basic therapy is better than that of antibiotics plus basic
      therapy. Reduning injection can improve the symptoms of cough and expectoration,
      shorten the fever time and facilitate the absorption of chest x-ray shadow
      without any significant adverse reactions. However, further high quality trials
      are needed.

PMID- 22368875
TI  - [Exploration on eighteen incompatible medicaments of chest pain prescriptions
      based on association rules mining].
AB  - OBJECTIVE: To investigate the laws of eighteen incompatible medicaments of the
      chest pain prescriptions based on association rules mining. METHOD: The database
      of chest pain prescription was established and then the chest pain prescriptions
      composed of eighteen incompatible medicaments were screened. The dynasty, couplet
      medicines, the property and flavor of drugs and preparation form were analyzed
      with the frequent item sets and corresponding analysis methods. RESULT: Eight
      hundred and fifty chest pain prescriptions were collected, and 88 of them
      contained eighteen incompatible medicaments, taking 10.3% of all; the
      applications of ancient and modern chest pain prescriptions containing eighteen
      incompatible medicaments are significant difference (P < 0.05). Ancient formulas,
      mainly focus on the eastern jin dynasty and tang dynasty, are more often used
      than the modern formulas. The most common anti-drugs is on the Fuzi-Pinellia,
      Chuanwu-Pinellia; the property and flavor of drugs is bitter cold most closely;
      the decoction of the formulas is mostly used. CONCLUSION: Eighteen incompatible
      medicaments account for about ten percent of the chest pain prescription, not an
      uncommon side. There are certain rules for application of anti-drug compatibility
      to treat chest pain.

PMID- 22368876
TI  - [Discussion on development of four diagnostic information scale for clinical re
      evaluation of postmarketing herbs].
AB  - Post-marketing re-evaluation of Chinese herbs can well reflect Chinese medicine
      characteristics, which is the most easily overlooked the clinical re-evaluation
      content. Since little attention has been paid to this, study on the clinical
      trial design method was lost. It is difficult to improving the effectiveness and
      safety of traditional Chinese medicine. Therefore, more attention should be paid
      on re-evaluation of the clinical trial design method point about tcm syndrome
      such as the type of research program design, the study of Chinese medical
      information collection scale and statistical analysis methods, so as to improve
      the clinical trial design method study about tcm syndrome of Chinese herbs
      postmarketing re-evalutation status.

PMID- 22368877
TI  - Plenty to look forward to in Manchester.
AB  - Many HEJ readers will first see this issue as they pick up a copy at Healthcare
      Estates 2011, IHEEM's flagship conference and exhibition in Manchester. Health
      Estate Journal looks ahead at some of the anticipated show highlights, and
      describes plans already in hand for next year's event, which is also set to be
      held at Manchester Central.

PMID- 22368878
TI  - Gold standard for Gold Coast facility.
AB  - Bill Geerlings, CEng, FIHEEM, FIHEA, BHA NSW, project director, on the A$1.76
      billion Gold Coast University Hospital in Southport, Queensland, describes how
      the team behind the new healthcare facility arrived at a design and plans for a
      hospital, due for completion late in 2012, that will not only provide modern,
      well-equipped patient, staff, and visitor facilities, but will also score highly
      on sustainability, urban design excellence, good access, innovation, and future
      proofing.

PMID- 22368879
TI  - Evolving education on waterfront campus.
AB  - Lorie Shekter-Wolfson, assistant vice-president, Waterfront, and Dean of
      Community Services and Health Sciences, at George Brown College in Toronto,
      describes the construction of a new waterfront campus for the College, where the
      aim is to provide a learning facility "flexible enough to evolve and shape future
      healthcare delivery models and assist collaborative learning".

PMID- 22368880
TI  - Legionella eliminated with no 'side-effects'.
AB  - Stuart Watkin BEng (Hons) MSc CEng MIHEEM, head of Engineering Compliance &
      Energy at North Tees & Hartlepool NHS Foundation Trust, reports on a recent six
      month trial, at the Trust's University Hospital of North Tees, of a new saline
      based disinfection system for combating Legionella. The system, from Danish
      company, DCW, has reportedly proven highly effective in keeping the water system
      at the test site, the hospital's North Wing, Legionella-free, impressing both
      estates and facilities/engineering personnel, and an independent consultant, with
      both its efficacy and lack of "side-effects".

PMID- 22368881
TI  - 'Parameters exceeded' at dedicated centre.
AB  - Health Estate Journal reports on the design and construction of the UK's first
      dedicated transplantation centre, at Newcastle's Freeman Hospital, considering
      some of the complex practical, adjacency, structural, and aesthetic challenges
      the project team had to overcome to create a facility designed to provide both
      leading edge medical training and research facilities, and a light, spacious, and
      uplifting patient and staff environment.

PMID- 22368882
TI  - MS facility will add crucial capacity.
AB  - With around a half of all construction projects over budget or missing their
      completion date, (according to Construction Statistics Annual, 2009, Office of
      Public Sector Information), David Jupp, business development manager at Elliott
      Off-Site Building Solutions, looks at why an off-site solution was chosen for the
      new West of England Multiple Sclerosis Centre in Bradley Stoke, North Bristol, a
      decision he says was largely driven by offsite's key advantages of enhanced
      design flexibility, factory-assured quality, faster completion, and less
      disruption and waste on site.

PMID- 22368883
TI  - Paddington hospital has 'world first' in AV.
AB  - Colin Dobbyne, director of OR1, describes OR Networks' recent installation of a
      sophisticated new video communication and patient entertainment system in the
      intensive care unit at London's St Mary's Hospital, explaining how the "world
      first" equipment was designed and manufactured to meet the Imperial College
      Healthcare NHS Trust's specific requirements. The specialist healthcare
      communications design consultancy also worked with clean air engineers, Howorth
      Air Technology, to provide a "package" of integrated equipment for a major
      theatre refurbishment at the hospital, whose past alumni include runner of the
      first sub-four-minute-mile, Sir Roger Bannister--later to become a distinguished
      neurologist.

PMID- 22368884
TI  - Expansion to allow 'new model of care'.
AB  - UK architecture firm, BMJ Architects, is well-known as a specialist in healthcare
      work, completing projects all over the UK--from whole hospital campuses to cancer
      care centres. The practice recently completed the design of a 3.5 million
      sterling pounds expansion to the existing Emergency Department at Glasgow Royal
      Infirmary (GRI), making the facility one of the biggest receiving complexes in
      Europe. HEJ reports.

PMID- 22368885
TI  - Simpler radioactive wastewater processing.
AB  - Jose Canga Rodriguez, key account manager, Pharmaceutical and Life Sciences,
      EnviroChemie, and Volker Luh, CEO of EnviroDTS, describe the development, and
      recent successful application, of a new technology for dealing safely and
      effectively with the radioactive "wastewater" generated by patients who have
      undergone radiotherapy in nuclear medicine facilities. The BioChroma process
      provides what is reportedly not only a more flexible means than traditional
      "delay and decay" systems of dealing with this "by-product" of medical treatment,
      but also one that requires less plant space, affords less risk of leakage or
      cross-contamination, and is easier to install.

PMID- 22368886
TI  - Getting it right from the ground up.
AB  - According to international heating system manufacturer, Viessmann, it is not only
      new construction projects that can benefit from renewable heating systems. Where
      the location is suitable, the retrofitting of solar, heat pumps, or biomass
      boilers to existing systems can dramatically reduce running costs "without too
      much disruption", Nigel Jefferson, the company's commercial sales director in the
      UK, told HEJ.

PMID- 22368887
TI  - University hospitals--design excellence.
AB  - University hospitals represent an infrastructure of strategic importance for any
      country. They allow an excellent standard of care to be attained by ensuring both
      a high level of training for health professionals (physicians and nonphysician
      practitioners), and the carrying out of biomedical and health research of
      international resonance. They may also be powerful promoters of biomedical
      innovation through technology transfer activities. Given their significance, it
      is important that research is undertaken both into the backdrop against which
      current university hospitals are designed, and the development of such
      establishments' role in the future, as well as into the optimal organisational
      model to respond, and adapt to, changes in medical education and care delivery.
      This article will consider the main issues that are the focus of international
      debate, highlighting design solutions of value to designers and researchers
      alike.

PMID- 22368888
TI  - The key to security is a balancing act.
AB  - Grant Macdonald, managing director at supplier of mechanical and electronic door
      locks, Codelocks, examines some of the important issues for healthcare estates
      and facilities personnel considering how best to protect parts of a healthcare
      facility--large or small--given the need to minimise costs and not "over-specify"
      on security, while simultaneously ensuring that patients, staff, and hospital
      property, are safeguarded.

PMID- 22368889
TI  - Endeavour delivers cancer care rewards.
AB  - Tony Roger, project manager at building services contractor, Shepherd Engineering
      Services (SES), describes the successful delivery of the 30 million sterling
      pounds New Oncology Expansion project at The James Cook University Hospital in
      Middlesbrough.

PMID- 22368890
TI  - Portable screens show multiple benefits.
AB  - Freelance healthcare journalist, Al Beah, considers the successful development,
      evolution, and expanding use in NHS hospitals, of the KwickScreen portable room
      divider, one of the products designed as part of the Department of Health's HCAI
      (Healthcare-Associated Infection) Technology Innovation programme, which was
      established in 2008 to speed up the development and adoption of technologies to
      help combat HCAIs such as MRSA and C. difficile. As he reports, the system is now
      not only being deployed to combat infection in hospitals and healthcare
      facilities both in the UK and overseas, but also for a wide variety of other
      uses.

PMID- 22368891
TI  - Health equity, quality of care and community based approaches are key to maternal
      and child survival in Pakistan.

PMID- 22368892
TI  - Intracoronary administration of autologous bone marrow stem cell transplant in
      myocardial infarction.
AB  - OBJECTIVE: To elaborate in detail the technique of intracoronary administration
      of autologous bone marrow stem cell transplantation in patients with acute
      myocardial infarction. METHODS: This procedure was carried out during a pilot
      study which was conducted in the department of interventional cardiology of Armed
      Forces Institute of Cardiology/National Institute of Heart Diseases Rawalpindi
      from June 2004 to November 2006. The inclusion criteria's were recent anterior
      myocardial infarction with anteroapical hypokinesia and single vessel disease in
      left anterior descending artery. The informed consent was obtained. After giving
      local anaesthesia and light sedation, both posterior superior iliac crests were
      accessed by multiple punctures to get stem cell harvest. The harvest was analyzed
      to document total and mean mononuclear cell count. An over the wire balloon
      catheter was parked in mid left anterior descending artery. The stem cells were
      injected intermittently into the infarcted myocardium during transient balloon
      inflation over 45-60 minutes. The clinical, left ventricle cineangiographic and
      nuclear scintigraphic parameters were analyzed and compared at week 0 and 12 to
      objectively document the effects of stem cell. RESULTS: The procedure was
      successfully carried out and well tolerated by all the patients. The minor
      complications were managed accordingly. Post autologous stem cell therapy, there
      was amelioration in clinical symptoms, left ventricle ejection fraction and
      myocardial perfusion. CONCLUSION: Intracoronary artery infusion of stem cells in
      acute myocardial infarction is simple, reasonably safe and effective mode of cell
      delivery in our set up.

PMID- 22368893
TI  - Bladder preservation by neoadjuvant chemotherapy followed by concurrent
      chemoradiation for muscle-invasive bladder cancer: experience at Sindh Institute
      of Urology & Transplantation (SIUT).
AB  - OBJECTIVE: To identify any additional benefit and note the safety profile of
      neoadjuvant chemotherapy prior to concurrent chemoradiation in muscle-invasive
      bladder cancer. METHODS: Forty three patients with T2b-T4N0M0 bladder cancer
      underwent maximal TURBT followed by neoadjuvant chemotherapy cisplatinum 75
      mg/m[2] D1+ gemcitabine 1000 mg/m[2] D1, D8 & D15 repeated every 28 days for
      three cycles followed by concurrent radiation 65Gy and weekly cisplatinum 30
      mg/m[2] or gemcitabine 100 mg/m[2]. Complete response (CR) was defined as no
      tumour seen on cystoscopy and biopsy. The disease control and overall survival
      were determined by Kaplan and Meier method and statistical inferences with the
      log-rank test. Cox regression analysis was used to find different prognostic
      factors. RESULTS: Out of 43, thirty two patients (78.04%) achieved CR at time of
      cystoscopic evaluation. Six patients who did not achieve CR (14.63%) underwent
      salvage cystectomies, remaining were not operable. At the median follow up of 36
      months, overall survival was 61%. Local recurrences were seen in 3 patients (10%)
      (2 pT1, 1pT2), distant metastases were seen in 2 patients (6.6%); 27/41 were
      alive, of whom 23 (56.1%) were retaining intact disease free bladders. The Tumour
      stage, incomplete TURBT and presence of hydronephrosis were important prognostic
      factors (log-rank p values 0.0001, 0.0001 and 0.001 respectively). CONCLUSION:
      Neoadjuvant chemotherapy followed by concurrent chemoradiation was tolerable with
      better bladder preservation and overall survival.

PMID- 22368894
TI  - Arthroscopic repair of meniscal tears with inside-out technique.
AB  - OBJECTIVE: To review the clinical results of arthroscopic meniscal repair and to
      identify factors that may affect the outcome. METHODS: A total of 15 arthroscopic
      meniscal repairs with inside-out in 14 patients over a 7-year period were
      evaluated retrospectively. The mean age was 41.2 +/- 11.5 years with a range of
      26-64 years. Eleven patients underwent repair for medial meniscal tear, two
      patients for lateral meniscus and one patient for both in the same knee. All
      patients were functionally evaluated by Lysholm functional knee scores over an
      average follow-up of 1 year and 5 months (range: 0.5-7 years). RESULTS: The mean
      Lysholm score was 84 out of a maximum of 100. Functional outcome was excellent in
      6 patients, good in 5, fair in 2 and poor in one patient. The patient with poor
      outcome was young with a chronic tear; she had concomitant ipsi-lateral
      radiculopathy and also had signs of reflex sympathetic dystrophy. One 64 year old
      patient with fair outcome developed a post-operative flexion contracture of 15
      degrees. She also had moderate osteoarthritis of the medial compartment. One
      patient developed saphenous nerve neuralgia which was relieved spontaneously
      after a few months. CONCLUSION: All patients with excellent results were
      relatively younger with an acute tear. Elderly patients with concomitant
      osteoarthritis of the knee joint did not have a satisfactory outcome even if the
      tear was acute.

PMID- 22368895
TI  - Pars plana surgical capsulotomy for posterior capsular opacification (PCO).
AB  - OBJECTIVE: To evaluate the safety and efficacy of pars plana surgical posterior
      capsulotomy in pseudophakic adults. METHODS: This prospective interventional case
      series was conducted at Sindh Govt Lyari General Hospital Karachi and Al- Noor
      Eye Hospital Karachi from June 2006 to May 2008. Complete ophthalmic examination
      of anterior and posterior segment was performed including assessment of type of
      posterior capsular opacification, measurement of intraocular pressure. Visual
      acuity, measurement of intraocular pressure and any unwanted complications were
      analyzed. RESULTS: Seventy six (43.18%) patients were operated on both eyes. Mean
      age was 62.01 +/- 13.02 years. There were 104 (59.1%) females and 72 (40.9%)
      males. Visual acuity at presentation was found to be 6/9 to 6/18 in 130
      (59.1%)eyes, 6/18 to 6/60 in 81(36.8%) and below 6/60 in 9 (4.1%) eyes. A
      significant reduction in intraocular pressure (13.8, +/- 1.4, P = 0.000) was
      noted on second post operative day. Intraoperative complication included
      subconjuctival haemorrhage in 22 (10%) eyes, pin head haematoma at the entry site
      in 7 (3.2%) eyes, pea head haematoma at the entry site in 8 (3.6%) eyes, minor
      grade of vitreous haemorrhage in 9 (4.1%) cases. Insufficient capsular opening
      was noted in 8 (3.6%) eyes. Clinically evident macular oedema in 4 (1.8%) eyes.
      We found no case of endophthalmitis or retinal detachment. CONCLUSION: Surgical
      posterior capsulotomy is a safe and effective procedure in experienced hands and
      could be adopted in place of YAG laser.

PMID- 22368896
TI  - A prospective study of cefepime versus ticarcilline/clavulanate as empirical
      treatment of febrile neutropenia in lymphoma patients.
AB  - OBJECTIVE: To check the effectiveness of ticarcillin clavulanate versus cefepime
      as monotherapy in febrile neutropenia in lymphoma patients and also to check
      tolerability profile of both drugs. METHODS: We randomly assigned 107 neutropenic
      patients to receive either cefepime or ticarcillin/clavulanate. The clinical
      efficacy and tolerability profile of both drugs were compared using either
      cefepime or ticarcillin clavulanate (TC) as an empirical treatment for management
      of febrile neutropenia in lymphoma patients only with same characteristics at
      time of presentation. RESULTS: A significant difference in efficacy of the two
      treatment arms was noted. A successful outcome was reported with 28 (51%) out of
      55 in cefepime arm compared to 16 (42%) out of 52 patients in
      ticarcillin/clavulanate group (p = 0.35; 95% Confidence). The distribution of
      time for defervesence was estimated for each treatment group and a trend to a
      shorter time for defervesence was found in the CEFEPIME group (48.4 hour for
      cefepime, 58.28 hour for TC group; p = 0.018). For microbiologically documented
      infections, the successful eradication rate was 49% (6 of 14 patients) for TC
      group as compared to 83% (10 of 12 patients) for cefepime group. This difference
      was statistically significant for microbiologically documented infections. Twenty
      seven (52%) patients of TC group and 19 (35%) of cefepime group required
      modifications of antibiotic regimen. The most frequent modifications consisted of
      the addition of either an amino glycoside (amikacin) or glycopeptides
      (vancomycin). CONCLUSION: CEFEPIME regimen was more effective than TC regimen,
      with a consistent trend toward a better outcome associated with cefepime compared
      to Ticarcillin/clavulanate.

PMID- 22368897
TI  - Prevalence and risk factors of renal tubular acidosis after kidney
      transplantation.
AB  - OBJECTIVE: To asses the prevalence of post-transplant renal tubular acidosis
      (RTA) and its associated risk factors. METHODS: A cross-sectional study was
      conducted on 100 live related renal transplant recipients, with a transplant
      duration of more than one year and an estimated GFR > 40 ml/min/1.73m2. Patients
      with acute graft rejection within last 6 months, unstable graft function, acute
      urinary tract infection and diarrhoea were excluded. Renal Tubular Acidosis (RTA)
      was diagnosed on the basis of plasma bicarbonate, venous pH, urine and serum
      anion gap measurements. RESULTS: Out of 100 patients (74 male, 26 female) RTA was
      observed in 40 (29 male, 11 female). Patients with RTA had a lower GFR (65.87 +/-
      12.35 versus 74.23 +/- 14.8 ml/min/1.73m2, P = 0.004) and higher number of
      previous acute rejections. Lower bicarbonate was associated with higher serum
      chloride (108.2 +/- 3.19 versus 105.72 +/- 3.9 mEq/L, P = 0.001) and higher
      potassium concentration (3.95 +/- 0.53 vs 3.61 +/- 0.46 mg/dl, P = 0.001). Higher
      phosphorous level (3.46 +/- 0.71 in RTA vs 3.19 +/- 0.59 mg/dl in non-RTA, P =
      0.045) but lower total serum calcium concentrations were found in patients with
      RTA. Intake of angiotensin converting enzyme inhibitors (ACE 1) was associated
      with the development of RTA. Calcineurin inhibitor (CNI) therapy was not
      associated with an increased likelihood of RTA. While no difference was noted in
      sex, age, pre-transplant dialysis duration, post transplant period, body mass
      index and serum albumin levels. CONCLUSION: There is a high prevalence of RTA in
      renal transplant recipients. In most of the patients, this is subclinical and
      does not require treatment.

PMID- 22368898
TI  - Efficacy and safety of quinine loading dose in patients with severe falciparum
      malaria at a tertiary care hospital in Pakistan.
AB  - OBJECTIVE: To compare the clinical outcomes of a loading dose regimen of quinine
      with a uniform dose regimen in patients with severe falciparum malaria. METHODS:
      A retrospective chart review of 315 patients admitted with severe falciparum
      malaria and treated with quinine at a tertiary care teaching hospital of Karachi,
      Pakistan during 1999-2006 was conducted. Group A with 103 patients (32.7%) was
      given an initial loading dose of quinine while group B with 212 patients (67.3%)
      did not receive the loading dose. The two groups were compared in terms of
      reduction of parasite load, resolution of fever, recovery of consciousness and
      incidence of adverse effects. Outcome parameters were measured on the third day
      of therapy. RESULTS: More individuals in group A (62.1%) were afebrile as
      compared to group B (54.7%) at day 3 of therapy. Patients in group B showed
      greater reduction in parasitaemia (47.2% at baseline to 4.7% on day 3) as
      compared to group A (56.3 % at baseline to 9.7% on day 3). Following therapy,
      fewer patients in group B had altered consciousness (7.1% at baseline to 4.7% on
      day 3) as compared to patients in group A (7.8% at baseline to 5.8% on day 3).
      However, these associations were not statistically significant. The incidence of
      thrombocytopenia was higher in Group A (5.8%) as compared to Group B (0.9%).
      CONCLUSION: Although quinine loading dose may be more effective than uniform dose
      in rapid fever clearance; it also appears to be associated with higher toxicity.
      Uniform dose of quinine may be prescribed in severe falciparum malaria in view of
      its better safety profile.

PMID- 22368899
TI  - Redo coronary artery surgery; early and intermediate outcomes from a tertiary
      care hospital in a developing country.
AB  - OBJECTIVE: To evaluate outcomes of re-operative coronary artery surgery in a
      tertiary care hospital in a developing country. METHOD: Preoperative, intra
      operative and postoperative variables were analyzed in 82 consecutive patients
      who underwent re-operative coronary surgery on cardiopulmonary bypass. RESULTS:
      The mean age was 63.3 +/- 7.7 years, 91.2% were male and 9.8% female. Coronary
      artery disease risk factors were present in more than 50% of the patients.
      History of preoperative myocardial infarction was positive in 56% patients. There
      was strong clinical and angiographic indication for surgery with unstable angina
      in 50% patients and > 80% had multivessel disease. Only 5% patients were in
      functional class I. The risk stratification showed a mean Euro score of 8. The
      IABP was used in 20% patients. A mean of 3.1 grafts per patient were applied. The
      median cardiopulmonary bypass (CPB) and aortic cross clamp time was 144 minutes
      respectively. Postoperative mortality was 7.3%. Short-term follow up revealed 74%
      of the patients in NYHA functional class I. CONCLUSION: Reoperative coronary
      artery bypass grafting is challenging but with expertise, team effort can be
      performed with good functional outcome.

PMID- 22368900
TI  - Causes and management of zygomatic bone fractures at Abbasi Shaheed Hospital
      Karachi (analysis of 82 patients).
AB  - OBJECTIVES: To assess the causes and management of Zygomatic bone fractures at
      Abbasi Shaheed Hospital, Karachi. METHODS: This study was carried out at
      Department of Oral & Maxillofacial surgery Abbasi Shaheed Hospital, Karachi. A
      total of 82 cases were studied. A detailed history was taken, clinical
      examination was performed and fractures were confirmed by radiography. Management
      of fractures was done by using different proposed modalities, suitable for every
      case. A number of factors, like age of patients, causes of trauma and gender were
      assessed. RESULTS: The commonest cause of Zygomatic bone fracture was found to be
      road traffic accident (RTA) 50% (n = 41), followed by assault 23.17% (n = 19),
      fall 20.73% (n = 17), sports injuries 3.65% (n = 3), and others 2.43% (n = 2)
      respectively. Right side (55%) was involved a little more than the left side
      (45%). Zygomatic bone fracture was more prevalent in age group between 21-30
      years, while male to female ratio was 5.30:1. Remote reduction using Gillie's
      Temporal Approach with and without fixation using bone plates were the commonest
      management modalities used in this center. CONCLUSION: The commonest cause of
      Zygomatic bone fracture was found to be road traffic accident, with the right
      side fractures being more common. It reveals poor road traffic sense in road
      users, lack of road safety measures and legislation in our population.

PMID- 22368901
TI  - Prevalence and risk factors for diabetes mellitus in a selected urban population
      of a city in Punjab.
AB  - OBJECTIVE: To estimate the prevalence of diabetes mellitus (diagnosed and
      undiagnosed), impaired fasting glucose and possible risk factors for diabetes
      mellitus among Pakistani population. METHODS: This cross sectional study was
      performed in Rawalpindi which is one of the cities in Northern Punjab of Pakistan
      in July 2008. An area was selected in Rawalpindi city, with mixed population
      representative of almost all provinces with different socioeconomic groups. Three
      hundred and thirteen houses were selected through systematic random sampling
      technique and fasting blood glucose was obtained and subjects were labeled to
      have diabetes according to WHO criteria of diagnosing diabetes mellitus. The
      statistical analysis was performed by using Stata version 10. RESULTS: There were
      1091 respondents who were selected after cleaning the data, among them 293 were
      males and 798 were females. Of the total 15.41% of the males and 12.31% of
      females were found to have diabetes mellitus. Thus making a total prevalence of
      13.14%. Impaired fasting glucose (IFG) was found in 5.14% males and 5.78% females
      making a total prevalence of 5.61%. Over all (DM & IFG) was found to be 20.55% in
      males and 18.09% in females. The main risk factors identified were obesity,
      family history, hypertension and increasing age. CONCLUSION: There is an
      increased prevalence of Type 2 diabetes in Pakistan and main risk factors
      identified were obesity, overweight, family history of diabetes mellitus, and
      hypertension.

PMID- 22368902
TI  - Accuracy of computed tomography in diagnosing malignancy in solitary pulmonary
      lesions.
AB  - OBJECTIVE: To evaluate accuracy of Computed Tomography (CT) for diagnosing
      malignancy in solitary pulmonary lesions (SPLs). METHODS: A prospective cross
      sectional study was conducted from 20-01-2007 to 30-06-2008 at the Radiology
      department, Aga Khan University Hospital (AKUH) Karachi. Fifty-three patients
      with solitary pulmonary lesions (SPLs) seen in prior chest x-rays or chest CT
      scans were referred to radiology department for CT guided biopsy. CT scan was
      performed for each patient prior to biopsy and CT evaluation of the SPLs was
      performed followed by CT guided Biopsy. Histopathological diagnosis of the lesion
      was taken as the gold standard. RESULTS: CT was found to be 100% sensitive, 30%
      specific and 87% accurate for diagnosing malignancy in solitary pulmonary lesions
      while PPV and NPV were 86% and 100% respectively. CONCLUSION: CT scan is highly
      sensitive yet non-specific and cannot be used as the definitive diagnostic
      modality for diagnosing malignancy in solitary pulmonary lesions.

PMID- 22368903
TI  - The role of leukocyte counts in patients with unstable angina pectoris or
      myocardial infarction; prognostic significance and correlation with plasma brain
      natriuretic peptide (BNP) levels.
AB  - OBJECTIVE: To study the role of leukocyte count in patients with unstable angina
      pectoris or myocardial infarction (Acute Coronary Syndrome) its prognostic
      significance and correlation with plasma brain natriuretic peptide (BNP) levels.
      METHODS: A total of 143 Patients with unstable angina pectoris, non-ST segment
      elevation MI and ST segment elevation MI were considered for entry into the
      study. Plasma BNP levels were measured using a commercial BNP kit (AxSym System
      BNP Reagent Pack, Abbott Laboratories, Abbott Park, IL, USA). Leukocyte count was
      measured on CELL DYNE counter of Abbott Laboratories. RESULTS: Mean age of the
      patients were 58.67 +/- 12.48 years. Mean leukocyte count was 9772 +/- 3006
      /cumm. In all 43 (30%) patients had high leukocyte count, and 82 (57%) patients
      had elevated BNP level. Out of 61 patients with normal BNP level, 49 (80%) had
      normal leukocyte count and 12 (20%) had elevated leukocyte count. Out of 82
      patients with elevated BNP level, 51 (62%) had normal leukocyte count and 31
      (38%) had elevated leukocyte count (P = 0.01). CONCLUSION: No statistically
      significant association was found between Leukocyte count and ACS. Although there
      is a trend of increased Leukocyte count noted in patients with increase BNP
      level. This finding necessitates further studies to elucidate its accurate
      significance.

PMID- 22368904
TI  - Severe malaria in children: factors predictive of outcome and response to
      Quinine.
AB  - OBJECTIVE: To identify clinical features of severe malaria and their association
      with adverse outcomes according to recently proposed WHO guidelines and observe
      treatment failure to Quinine. METHODS: This descriptive study was performed at
      Civil Hospital Karachi from September 2007 to January 2008. Various clinical
      features and laboratory parameters were analyzed according to t WHO guidelines
      and treatment failure to anti-malarial drugs was recorded. Mean, frequencies,
      percentages and chi-square test were used for analysis. Statistical significance
      was defined as p-value < 0.05. RESULTS: Total of 81 patients were enrolled in the
      study. Mean age of children was 5.5 +/- 3.4 years. Type of malaria infections
      that were seen included falciparum 46 (57%), mixed infection 26 (32%) and vivax 9
      (11%). Frequent clinical features included splenomegaly (74%), multiple organ
      dysfunction (MOD) (70%), cerebral malaria (31%) and malnutrition (27%).
      Thrombocytopenia (86%) and severe anaemia (42%) were the common laboratory
      findings. Shock (p < 0.001), renal failure (p < 0.001), hepatic involvement (p <
      0.002) and cerebral malaria (p < 0.002) emerged as strong predictors of
      complications. Fourteen out of 81 cases showed early treatment failure to
      Quinine. CONCLUSION: Shock, renal failure, hepatic involvement and cerebral
      malaria are strongly associated with complications in severe malaria. MOD and
      malnutrition were identified as significant new clinical features present in
      severe malaria in this study.

PMID- 22368905
TI  - Anthropometric measurements as a risk for hypertensive disorders in pregnancy: a
      hospital based study in South Asian population.
AB  - OBJECTIVE: To determine the relationship between pregnancy induced hypertensive
      diseases and obesity. METHODS: A retrospective case controlled study was
      performed at Aga Khan University Hospital including records from July 2000 to
      June 2005. All women developing hypertension with or without proteinuria after 20
      weeks of pregnancy (n = 218) were included. Categories of pregnancy induced
      hypertensive diseases (PIHD) were defined according to National high blood
      pressure working group and ACOG committee bulletin. Controls were selected
      randomly with a ratio of 1:1.7 between cases and controls. RESULTS: The estimated
      prevalence of pre-eclampsia in our institution is 1.9%. Earlier reports suggested
      mostly non-Asian women primigravida were more likely to develop gestational
      hypertension when compared with multigravidae (p-value = 0.004). Mean BMI of
      cases was significantly higher than controls (p = < 0.001). The risks of both non
      protienuric hypertension (Mean BMI = 27.16 +/- 5.46) and preeclampsia (Mean BMI =
      27.39 +/- 6.15) increased consistently with increasing BMI. This rise was
      significantly associated with severity of pre-eclampsia and early development of
      PIH, but not associated with complications like eclampsia. No significant
      association of height and hypertension was found as most women of both cases and
      control were 150-165 cm tall. CONCLUSIONS: High BMI in pregnant women serves as a
      significant risk factor for developing hypertension in pregnancy but failed to
      establish this association with height is the main findings of our study.

PMID- 22368906
TI  - Needlestick injuries: a survey of doctors working at Tertiary Care Hospitals of
      Rawalpindi.
AB  - OBJECTIVES: To document frequency, nature and predisposing factors for
      needlestick injuries (NSI) in doctors working at tertiary care hospitals of
      Rawalpindi. METHODS: This cross sectional survey was conducted at Department of
      Medicine, Rawalpindi Medical College from July 2009 to April 2010. Five hundred
      doctors working at various tertiary care hospitals of Rawalpindi were contacted.
      Each doctor was provided a specifically designed proforma focusing on number,
      nature, and predisposing factors for NSI which was defined as percutaneous injury
      caused by hollow-bore needles, suturing needles, scalpel blades and lancets.
      Frequency and percentage of collected data was sought. RESULTS: Out of 500, 61.8%
      (n = 309) doctors returned the filled proformas. Females were 50.8% (n = 158).
      History of NSI was present in 85.1% (n = 263) participants of which most common
      was from syringe needle (47.52%; n = 125), surgical stitch needle (20.9%; n =
      55), and surgical blade (9.5%; n = 25). Most of NSI took place while recapping
      needles (33%; n = 87), surgical procedures (27.7%; n = 73), and drawing blood
      samples (26.2%; n = 69). Majority of these doctors 42.5% (n = 112) attributed NSI
      to stress, 37.6% (n = 99) to over work, and 19.7% (n = 52) to carelessness.
      CONCLUSION: NSI due to syringe and surgical stitch needle are very frequent in
      doctors working at various tertiary care hospitals of Rawalpindi. Most of these
      are sustained while recapping needle and surgical procedures in stressful and
      overworked circumstances.

PMID- 22368907
TI  - An analysis of interactive hands-on workshops on medical writing.
AB  - OBJECTIVE: To assess the improvement in participant's knowledge and skills
      pertaining to medical writing by interactive hands-on workshops. METHODS: During
      the course of three months (January to March 2009), four interactive 5 hours
      hands-on workshops were organized on Medical Writing. All participants completed
      a pre-workshop and post-workshop questionnaire. Fourteen questions were included
      in both questionnaires related to workshop outline. Eight questions were related
      to knowledge of the participants about different aspects of medical writing
      (yes/no). Participants were also asked six questions to rate their skills
      relating to medical writing on a numerical scale of 1-5 (1: no skills and 5:
      expert). Participant's feedbacks were also analyzed. The pre-workshop and post
      workshop responses were compared to see if there was any significant difference
      by using McNemar test and paired-t test where appropriate. RESULTS: Response to
      eight questions regarding knowledge (authorship criteria, types of data,
      application of significance test, search techniques, plagiarism, Vancouver style
      of reference and copyright statement) showed that there was a significant
      difference in all responses (p < 0.005). Same trend was observed in skills rating
      (literature search, basic data analysis, writing an original article, writing
      references, paper submission for publication) of participants themselves before
      and after the workshop (p < 0.0001). Analysis of feedback showed that
      participants found the workshop informative, practical and helpful in improvement
      of their skills for paper writing. CONCLUSION: Short interactive hands-on medical
      writing workshops are helpful and beneficial in improving the knowledge and
      skills of the participants.

PMID- 22368908
TI  - Significance of pyuria in the diagnosis of urinary tract infections in neonates.
AB  - OBJECTIVES: To determine the significance of pyuria as a predictor of culture
      proven urinary tract infections (UTI) in neonates and to assess the frequency of
      urinary tract anomalies in neonates with pyuria. METHODS: Prospective study
      conducted at the neonatal intensive care unit of a tertiary care hospital;
      (Liaquat National Hospital Karachi) for a period of 4 months from April 2008 to
      August 2008. One hundred and ten consecutive infants < or = 28 days of age
      admitted to the NICU of Liaquat National Hospital for medical reasons were
      included in the study. Information regarding age, gender, antenatal history,
      birth weight, clinical examination, laboratory findings and outcome were recorded
      on a questionnaire. Septic work up was performed and urine samples were collected
      using urethral catheterization. Patients showing any number of white blood cells
      on microscopy were included and their urine sent for culture. All patients had
      Ultrasound done during their hospital stay and those patients with any renal
      abnormality were further investigated with Micturating cyestoretherogram (MCUG)
      at 6 weeks. RESULTS: Out of one hundred and ten patients admitted, thirty five
      patients showed the presence of pus cells in urine and were included in the
      study. Of the 35 neonates with pyuria, 71.4% had no growth in urine cultures and
      38.2 % neonates with insignificant pyuria (< or = 9 cells in urine) showed a
      positive culture. The renal ultrasound was normal in 51.4% neonates with pyuria
      although it was abnormal in 100% of the subjects with higher number of pus cells
      in urine (> 20 pus cells). CONCLUSION: Pyuria is not a useful marker for the
      diagnosis of culture proven UTI in neonates it cannot be used as an indicator of
      underlying renal abnormality, though it may have some utility in neonates with >
      20 /numerous pus cells.

PMID- 22368909
TI  - Suicide bombing: a geopolitical perspective.
AB  - Suicide bombing is a very complex phenomenon. It has been a focus of research in
      recent times. However inherent biases of researchers muddle the picture:
      researchers from western countries focus the issue around political liberty and
      notion of democracy, while those from Islamic countries tend to take the
      afterlife-reward notion as an incentive for suicide bombing. However in order to
      understand this complex phenomenon it is important to consider the contextual
      factors. In this review we have attempted to highlight various geopolitical
      factors which contribute to increased incidence of suicide bombing in South East
      Asia.

PMID- 22368910
TI  - Knowledge attitude and perception of dispensing doctors regarding generic
      medicines in Karachi, Pakistan: a qualitative study.

PMID- 22368911
TI  - Primary epiploic appendagitis: 3 case reports.
AB  - Acute Epiploic Appendagitis is a rare self limiting disease that represents
      ischaemic infarction of an epiploic appendix. It is usually discovered
      incidentally on imaging of abdomen done for other causes of acute abdominal pain.
      It is difficult to diagnose clinically due to the lack of pathognomonic clinical
      features, since it is characterized by a sudden onset of sharp localized pain
      either in the left or right iliac fossa with minimal gastrointestinal symptoms,
      which can simulate a surgical clinical picture. Awareness of imaging findings of
      this entity is important to arrive at a correct diagnosis and to avoid
      unnecessary hospitalization and surgery. We report cases of three male patients
      presenting with acute flank pain who were diagnosed as case of Primary epiploic
      appendagitis. All 3 patients were treated conservatively.

PMID- 22368912
TI  - Anaesthetic challenges in emergency surgical repair of acute aortic dissection
      rupturing into the pericardium in a pregnant patient.
AB  - Acute aortic dissection in pregnancy is a serious situation, because rapid and
      appropriate surgical decision making is required to save the life of both mother
      and baby. Aortic dissection is rare in young women but is likely during pregnancy
      (third trimester) secondary to the hyperdynamic and hypervolaemic circulatory
      state associated with pregnancy. A 35 years old 27 weeks pregnant patient
      weighing 90 kg presented in the emergency with severe chest pain. In the
      immediate post cardiopulmonary bypass period, the patient started bleeding
      profusely from the anastamotic sites irrespective of utilization of all the
      conventional methods of haemostasis including multiple units of whole blood,
      fresh frozen plasma, platelets, calcium and cryoprecipitates. As a last resort
      she was given low dose r FVIIa (1.2 mg containing 60 KIU of Factor VII). This
      stopped the bleeding and the haemodyramics were stabilized.

PMID- 22368913
TI  - Blood infection with Enterobacter aerogenes--an unusual cause of portal vein gas.
AB  - Portal vein gas was once thought of as an invariably fatal condition. Now, with
      the availability of better equipment and expertise, the condition is more
      frequently diagnosed. A case of fever with rigors is presented and on ultrasound
      and CT examination was found to have portal venous gas which resolved with
      adequate antibiotic treatment. Blood culture revealed growth of gram negative
      bacillus; Enterobacter aerogenes. Patient was investigated further for portal
      vein gas, and although no other cause for the development of portal vein gas was
      found, she was treated with antibiotics and showed an immediate response. The aim
      of this case report is to highlight the benign causes of portal vein gas as well
      as to discuss the causes which warrant immediate surgery. Portal vein gas may
      herald a more ominous condition, which if intercepted in its course may result in
      complete cure.

PMID- 22368914
TI  - Percutaneous transvenous mitral commissurotomy (PTMC) and percutaneous coronary
      intervention (PCI) successfully applied in one patient in same sitting.
AB  - Sixty years old male with severe rheumatic mitral stenosis (MS), presented with
      dyspnoea New York Heart Association (NHYA) class III to IV. Coronary angiogram
      revealed severe occlusive coronary artery disease in left anterior coronary
      artery (LAD). Percutaneous Transvenous Mitral Commissurotomy (PTMC) and
      Percutaneous Coronary Intervention (PCI) of Left Anterior Descurery (LAD) were
      done in same sitting. Both procedures were successful and ended without
      complication. After, half an hour while shifting to coronary care unit (CCU)
      patient developed cardiac tamponade, which was managed successfully. Patient was
      followed up for three month, he is doing well and recent echocardiogram showed
      mild mitral stenosis with normal left ventricular function. This case
      demonstrates the feasibility of the combined appliance on interventional
      techniques in selected patients as an alternative to cardiac surgery.

PMID- 22368915
TI  - Corruption in medical practice: how far have we gone?

PMID- 22368916
TI  - What modifiable risk factors lead to strokes in our part of the world?

PMID- 22368917
TI  - Road rage behaviour and experiences of taxi drivers in Islamabad and Rawalpindi,
      Pakistan.

PMID- 22368918
TI  - Terrorism and health: the responsibility of intellectuals?

PMID- 22368919
TI  - Perception and practices of breastfeeding of infants 0-6 months in an urban and a
      semi-urban community in Pakistan: a cross-sectional study.
AB  - OBJECTIVE: To investigate mother's perception and practices about breastfeeding
      and their socio-demographic correlate in infants equal to or less than 6 months.
      METHODS: A cross-sectional study was carried out on 200 mother-infant pairs who
      visited the health care centers, Bilal Colony (semi-urban) and the Aga Khan
      University (urban), for their well baby follow-ups and vaccination using
      convenient sampling. Frequencies and percentages were computed and Chi-square was
      used to find associations between socio-demographics of mothers and their
      perception and practices about breastfeeding. RESULTS: Exclusive breastfeeding
      was reported by about 54% of the mothers. Thirty-five percent of the mothers gave
      prelacteal feed, 14% discarded colostrum and 43% woke up their infant to feed if
      time had exceeded 2 hours. Majority of the females were aware of the advantages
      (92%) and the disadvantages (85%) of breastfeeding. However, the awareness of
      positive feedback relationship of milk production and sucking was lacking and
      breast feeding was considered to cause weakness in mothers. CONCLUSION: Despite
      the efforts of health policy makers, the results show a situation that is not
      improving. Women were aware of the advantages and disadvantages of breast and
      bottle feeding but a disparity was observed between their perception and
      practices.

PMID- 22368920
TI  - Effect of fasting after exercise on blood lactate clearance in untrained male
      volunteers.
AB  - OBJECTIVES: To determine the effect of fasting immediately after exercise on
      blood lactate clearance. METHODS: This study was conducted at College of
      Medicine, Dammam University, KSA. Untrained male volunteers (n = 26) between 18
      23 years of age were divided into two equal groups; fasting and non-fasting.
      After an overnight fasting both groups were made to exercise on a bicycle
      ergometer starting with 100 watt resistance with 25 watt increment after every 2
      minutes until voluntary exhaustion. The fasting group was then asked to continue
      fasting 30 minutes after exercise, while the non-fasting group was given 600 ml
      of carbohydrate-rich (about 16g per 100 ml) drink immediately after exercise. We
      measured the blood lactate level before, immediately after, and 30 minutes after
      exercise in both the groups. RESULTS: A significant (p < 0.001) increase in mean
      blood lactate level was observed in both the groups immediately after exercise as
      compared to the baseline means. Similarly there was a significant (p < 0.001)
      drop of lactate level in both the groups 30 minutes after exercise as compared
      with the blood lactate level immediately after exercise. There was a significant
      (p < 0.001) difference between the number of subjects with a blood lactate drop
      of more than 50% between the two groups (84.61% of subjects in the fasting group,
      versus 46.15% in the non-fasting group). CONCLUSION: Fasting after exercise
      accelerates lactate clearance from blood, probably by utilizing gluconeogenesis
      pathway.

PMID- 22368921
TI  - Chromogranin A--serum marker for prostate cancer.
AB  - Prostate Cancer is the second most prevalent neoplasm after lung cancer in men.
      It commonly presents in patients with a strong family history. The measurement of
      Prostate Specific Antigen (PSA) in free and bound forms is one of the methods to
      diagnose it. It is very much useful for monitoring the therapeutic efficacy,
      staging, prognosis, tumour volume evaluation, detection of recurrent disease,
      screening and early diagnosis. Chromogranin A (CgA) is an acidic glycoprotein
      that is commonly expressed by neuroendocrine cells and constitutes one of the
      most profuse components of secretory granules. When a tumour develops in an
      endocrine tissue, it becomes the main source of circulating CgA. Its
      concentration is thought to be elevated in relation to neuroendocrine
      differentiation of prostate cancer. CgA is a useful predictive marker in patients
      with prostatic cancer who have lower PSA. It is known that neuroendocrine cells
      in the prostate do not contain androgen receptors and are not regulated by
      androgens. PSA expression was stimulated by androgen through androgen receptors,
      so it is suggested that cases of prostate cancer associated with low serum PSA
      and high serum CgA, which would have more neuroendocrine cells with less androgen
      receptors, may show resistance to endocrine therapy and a poor prognosis.
      Therefore serum CgA tends to be elevated in high grade prostate cancer cases.
      Hence it can be used to fill the gap if any left by PSA when combined with serum
      PSA, the serum marker may effectively predict the prognosis after endocrine
      therapy. CgA expression in prostate cancer biopsies is an independent
      extrapolative factor of hormone refractory disease in patients with newly
      diagnosed prostate cancer on early androgen deprivation therapy.

PMID- 22368922
TI  - Smouldering systemic mastocytosis: a rare disorder with a difficult diagnosis.

PMID- 22368923
TI  - [Albinos in Africa].

PMID- 22368924
TI  - [Drug abuse and HIV in West Africa].

PMID- 22368925
TI  - [Should yellow fever vaccination be recommended during pregnancy or
      breastfeeding?].
AB  - Yellow fever vaccine is produced from a live attenuated virus that is
      contraindicated in case of immunodeficiency and subject to restrictions for
      pregnant or breastfeeding women. The purpose of this review of available
      information on yellow fever vaccination during pregnancy and breastfeeding is to
      assist physicians in making recommendations prior to departure to yellow-fever
      endemic zones. Regarding pregnancy, there is no evidence to support a major risk
      of yellow-fever-vaccine-related complications in mothers or children. Although
      this finding is reassuring, it should be underlined that most reported series
      have been small. Regarding breastfeeding, the risk was recently confirmed by a
      report describing vaccine-induced encephalitis occurring in an infant 8 days
      after primary vaccination of the mother. The final decision to vaccinate depends
      on whether or not the trip can be postponed. If travel is mandatory, vaccination
      may be recommended in pregnant women preferably during the first trimester since
      the immunological response appears to be better at that time. Antibody titer
      should be checked following delivery. During breastfeeding, vaccination may be
      performed but breastfeeding must be stopped during the postvaccinal viremia
      phase. Breastfeeding can be resumed after a 10-day period of formula feeding.

PMID- 22368926
TI  - [Vaccinal strategies in response to new epidemiological challenges in 2010.
      Reasonable hope for a "B" meningococcal vaccine].
AB  - In 2010, vaccines have achieved good effectiveness against invasive meningococcal
      infection. Development of monovalent and bivalent polysaccharide (PS) vaccines in
      the 70s and later of tetravalent PS vaccine (ACWY) was followed by development in
      2003 of a trivalent ACW vaccine in response to the W135 or mixed A/W135 epidemics
      that appeared in Africa. More recently PS-conjugated vaccines have shown numerous
      advantages in comparison with PS vaccines. Mass vaccination campaigns with the C
      conjugated vaccine have almost completely eradicated group C meningitis in the
      UK. It is hoped that introduction of the A-conjugated vaccine MenAfriVac in
      Africa at the end of year 2010 will end group A meningococcal epidemics in the
      meningitis belt. The problem of group B meningococcal meningitis has not been
      completely resolved. For the B strain that has been implicated in hyperendemic
      waves, a protein vaccine has been produced from outer membrane vesicles (OMV).
      Use of OMV vaccines achieved good results in Norway and recently in New Zealand.
      The Norwegian vaccine was also used in Normandy since the strain responsible for
      the Norman epidemic showed the same PorA as the Norwegian strain. In this regard,
      a major limitation for OMV vaccines is that they are effective only against the
      immuno-dominant porin A protein. Current efforts to develop a vaccine against
      group B meningococci causing sporadic cases are promising. Research is being
      focused on a blend of surface proteins targeting most of circulating isolates.
      Field tests will be carried out in the next years, but it is probable that the
      efficacy of these vaccines will be short-lived since meningococcal antigens vary
      over time.

PMID- 22368927
TI  - [Scrofuloderma leading to discovery of primary sternal tuberculosis].

PMID- 22368928
TI  - [Representation of illness in Mandingo society].
AB  - The Mandingo people are a 10-million strong ethnic group spread over several
      countries in West Africa but sharing a common culture. In Mandingo society that
      is permeated by a notion of sacredness, illness is represented in a much
      different way from contemporary European society. Because health is integrated
      into the social and religious structure, illness is associated with
      interpretations and preventive rules of conduct. For Western medical teams
      working in Mandingo communities, knowledge of these cultural implications is
      essential to establishing a good relationship with patients and to ensuring
      quality of care.

PMID- 22368929
TI  - [Triclabendazole].
AB  - Triclabendazole is indicated for treatment of human fascioliasis, a widespread
      disease. Treatment is straightforward and generally well tolerated. However,
      increasing resistance to this therapy has been observed since the 1990s. Research
      is being carried out to develop new medications with special interest in
      artesunate.

PMID- 22368930
TI  - [Rheumatic disorders observed in HIV infected patients undergoing highly active
      antiretroviral therapy (HAART): a 366 case prospective study in Burkina Faso].
AB  - OBJECTIVE: The purpose of this report is to describe epidemiological aspects of
      rheumatic disorders observed in HIV-infected patients undergoing highly active
      antiretroviral therapy (HAART). Patients and methods. This cross-sectional study
      was conducted from January 1 to June 30, 2008 in the HIV unit of an internal
      medicine department in Burkina Faso. All patients who had been undergoing HAART
      for at least one year were included. Interviewing and thorough physical
      examination were performed in all cases. Radiography of the pelvis and hip was
      performed in some patients. Bone densitometry was never performed. RESULTS: A
      total of 366 patients including 265 women and 101 men (sex ratio of 0.38) were
      included. Mean patient age was 39.61 +/- 8.54 years. Three hundred and thirty
      five patients (91.53%) were positive for HIV1, 17 (4.64%) for HIV2 and 14 (3.83%)
      for both HIV1 and HIV2. Mean duration of infection was 3.58 +/- 1.88 years. Mean
      CD4 cell count was 394.20 cell/microL. A recent HIV viral load determination was
      available for 285 patients including 262 who had no detectable virus. Mean
      duration of HAART was 35.80 +/- 15.17 months. Only 61 patients (16.66%) were
      treated with protease inhibitor (PI). The prevalence of rheumatic disorders was
      5.73% (21 cases). A variety of disorders were observed, i.e., lower back pain in
      8 patients (38.1%), arthralgia in 4 patients including 2 treated with PI,
      osteoarthritis of the knee in 2 patients, Pott disease in 2 patients, De Quervain
      disease in 2 patients including one treated with PI, tendinitis of the shoulder
      in one patient treated with PI, gout in one patient treated with PI and
      unclassifiable inflammatory rheumatism in one patient. No case of symptomatic
      osteonecrosis or osteoporosis was observed. CONCLUSION: Rheumatic disorders are
      uncommon in the HIV-infected patients undergoing HAART in Burkina Faso. The most
      likely explanation is that PI is not widely used.

PMID- 22368931
TI  - [Malaria and HIV infection: clinical and biological aspects at Donka National
      Hospital in Conakry, Guinea].
AB  - Malaria and HIV/AIDS are two of the most widespread infectious diseases
      encountered in sub-Saharan Africa. Even minor interactions between these two
      diseases could have substantial effects on public health. The purpose of this
      study was to investigate associations between malaria and HIV infection. Study
      was carried out over an 8-month period (April 1, 2003 to November 30, 2003) in
      the Tropical and Infectious Diseases Department of the Donka National Hospital in
      Conakry, Guinea. A total of 89 malaria patients including 41 cases with HIV
      infection and 48 controls without HIV infection were included. All patients were
      hospitalized during the study and provided informed consent. Results showed that
      malaria affected all age groups in the same proportion. Mean patient age was 34
      years (range, 15 and 76 years). Males were more frequently infected with a sex
      ratio of 1.05. The average number of malaria episodes was higher in cases
      (malaria with HIV-infection than in controls (malaria without HIV infection).
      Hyperthermia was observed in most cases (68.29%) and controls (77.08%). Severe
      anemia was observed in 26.82% of cases versus 10.41% of controls. Low parasite
      density was observed in 73.17% of cases as compared to 68.75% of controls. The
      recovery rate was higher in the control group than in case group: 27.08% versus
      14.63%. The death rate was higher in the case group than in the control group:
      21.95% versus 6.25%. These findings demonstrate a link between malaria and HIV.
      The frequency of malaria episodes was higher in patients with HIV infection than
      patients without HIV infection and the outcome of malarial episodes was better in
      patients without HIV infection.

PMID- 22368932
TI  - [Seasonal variations in the nutritional status of nomad and sedentary children
      less than 5 years of age living in the Sahel in Chad].
AB  - Malnutrition is widespread among rural and nomad populations in the Sahel. It is
      linked to socio-economic factors and exhibits significant seasonal variations.
      The aim of this study was to assess the prevalence of malnutrition and associated
      risk factors among children less than 5 years of age. A repeated cross-sectional
      study design based on interviews and anthropometric measurements was used. A
      total of 653 nomad children and 579 sedentary children ranging in age from 0 to
      59 months were randomly selected in households/camps on the south-eastern shore
      of Lake Chad. Data were collected from the same number of children at the end of
      the dry season (May/June, 2007) and at the end of rainy season (October 2007).
      Findings showed significant interseasonal variation in the prevalence of global
      acute malnutrition (GAM) between the end of the dry season and end of the rainy
      season. The respective variations were 17.9% to 13.7% (p = 0.03) in nomad
      children and 16.5% to 10.6% (p = 0.004) in sedentary children. Backward stepwise
      multivariate analysis by logistic regression showed that GAM among children under
      5 years of age was significantly correlated with the following risk factors:
      seasonal variation, child's age, mother's nutritional status, ethnic group, and
      place of residence (LRT=172 and p < 0.001 for the logistic regression model).
      These findings demonstrate the critical state of the nutritional situation in the
      Sahel and rural areas.

PMID- 22368933
TI  - [Is the mother a risk factor for transmission of Helicobacter pylori infection in
      children between the ages of 6 months and 5 years in Cote d'Ivoire?].
AB  - OBJECTIVES: The goals of this study were to determine the prevalence of H. pylori
      antibodies in children, to establish the relationship between child and mother
      serostatus, and to identify potential risk factors for contamination. MATERIAL
      AND METHODS: A cross-sectional study was conducted over a 3-month period. All
      children between 6 months and 5 years of age examined in the Pediatrics
      Department of the University Hospital Center in Yopougon, Cote d'Ivoire were
      included after obtaining informed consent from their mothers. Testing for H.
      pylori antibodies using Pylorix (Acon) was performed in both children and
      mothers. Based on test results, children were divided into two groups, i.e. case
      group with H. pylori antibodies and control group without H. pylori antibodies.
      Case and control groups were compared according to the H. pylori status of their
      mother and several potential lifestyle and environmental factors. RESULTS: A
      total of 101 children and 101 mothers were included. The prevalence of H. pylori
      antibodies was 40.6% in mothers and 24.8% in children. The mean age of children
      (53% male) was 22.8 +/- 15.6 months (median, 18 months). The mean age of the
      mothers was 29.6 +/- 5.5 years (range, 19 to 46 years; median, 29 years). Most
      mothers, i.e., 78.2%, lived in two-parent households but 19% lived in single
      parent settings (community or shacks). The number of persons living in the same
      house ranged from 2 to 20 people (mean, 7.2 +/- 3.8; median, 6 people). Mean
      monthly household income was 226,188 +/- 161,425 FCFA (range: 30,000 - 750,000
      FCFA). In the case group, 80% of children had mothers infected with H. pylori. In
      the control group, 73.7% of children had non-infected mothers (OR = 11.2, p <
      0.001). Median income was less than 150 000 FCA in 76% of families with
      seropositive children in comparison to 46.1% of families with seronegative
      children (p = 0.009). CONCLUSION: This study confirms the early occurrence of H.
      pylori infection in children. Findings also showed that poor socio-economic
      condition was a risk factor for infection but the greatest risk factor was living
      with a mother infected with H. pylori.

PMID- 22368934
TI  - [Management of ectopic pregnancy using methotrexate in Madagascar].
AB  - The purpose of this retrospective study was to evaluate the use of methotrexate
      for management of ectopic pregnancy in a series of 64 patients treated at the
      General Hospital Center in Soavinandriana, Madagascar from March 2005 to March
      2008. The success rate was 80%.

PMID- 22368935
TI  - [Helicobacter pylori and gastroduodenal lesions in Dakar, Senegal].
AB  - INTRODUCTION: The bacteriological characteristics of Helicobacter pylori (HP)
      vary in function of time and place. The aim of this study was to update
      histological and bacteriological feature of HP infection in patients presenting
      gastroduodenal lesions in Dakar, Senegal. PATIENTS AND METHOD: This prospective
      study included patients with gastroduodenal lesions managed over a 6-month period
      in a digestive endoscopy center in Dakar. In all cases gastric biopsy was
      performed to obtain specimens for histological diagnosis according Sydney
      modified classification and HP culture with antibiogram. RESULTS: A total of 158
      patients were included. Mean patient age was 48.7 years and the sex-ratio was
      1.2. Endoscopic lesions were ulcer in 88 cases, gastritis in 54 cases and tumors
      in 16. Histological examination demonstrated chronic gastritis in 100% of cases,
      inflammatory activity in 79.1%, metaplasia in 78.5%, gastric atrophy in 41.1%,
      adenocarcinoma in 7.6%, dysplasia in 5.7%, and MALT lymphoma in 2.5% with
      presence of HP in 72.8% of cases. Cultures were positive for HP in 65.8% of
      cases. Antibiograms indicated that HP was sensitive to amoxicilline in 100% of
      cases, clarithromycine in 96.6%, ciprofloxacine in 84.1%, and metronidazole in
      29.5%. CONCLUSION: Chronic gastritis is a constant feature of gastroduodenal
      lesions in Dakar. Histology combined with culture showed HP infection in 78.5% of
      cases. The antibiotic sensitivity of HP in Dakar has changed over the past
      decade.

PMID- 22368936
TI  - [Atrial fibrillation: epidemiological data from the Cardiology Institute in
      Abidjan, Cote d'Ivoire].
AB  - The purpose of this retrospective study covering a 10-year period was to analyze
      epidemiological data and associated conditions related to atrial fibrillation
      (AF) in a cardiology hospital setting in SubSaharan Africa. PATIENTS AND METHODS:
      A total of 217 charts of patients hospitalized in the Medical Department of the
      Abidjan Cardiology Institute between August 1995 and August 2005 were reviewed.
      RESULTS: During the study, a total of 3,908 patients were admitted to the
      department, including 217 for AF for a hospital prevalence of 5.5%. There were
      113 men (52%) and 104 women (48%) for a sex ratio of 1.08. Overall mean patient
      age was 58.9 years (range, 18 to 91 years). The difference in the mean age of men
      and women was not statistically significant: 57.8 versus 60 years respectively.
      The main symptoms at the time of admission to the hospital were exertional
      dyspnea (55.7%) and palpitations (22.1%). A total of 136 patients (62.6%)
      exhibited cardiac insufficiency. Heart disease was diagnosed in 192 patients
      including hypertensive cardiopathy in 48% and rheumatic valvular heart disease in
      28%. The thromboembolic risk was moderate in 47% of patients (CHADS2 score,
      between 1 and 2) and high in 18.4% (CHADS2 score > or = 3). CONCLUSION: In our
      practice, hypertensive and rheumatic valvular heart disease were the main causes
      of AF that was associated with an alarming thromboembolic risk. These findings
      indicate that further effort is needed to prevent arterial hypertension and acute
      rheumatic joint disease.

PMID- 22368937
TI  - [Liver cirrhosis in Cotonou, Republic of Benin: clinical aspects and factors
      related to death].
AB  - Infection by hepatitis B virus is the main cause of liver cirrhosis in Africa.
      The purpose of this retrospective study was to evaluate clinical and
      epidemiological features as well as factors related to death in cirrhosis
      patients admitted to the National University Hospital in Cotonou, Benin. METHODS:
      The files of patients admitted from January 1 to December 31, 2004 were reviewed.
      RESULTS: Out of the 230 useable files reviewed, a total of 52 involved patients
      were admitted for liver cirrhosis. The male/female sex ratio was 2.25 and mean
      age was 49 years. The proportion of unemployed and salaried patients was 42.3%
      and 28.8% respectively. Hepatitis B and alcohol consumption were the main
      etiological factors: 53.3% and 23.2% respectively. The main reasons for
      hospitalization were asthenia in 73% of cases, abdominal pain in 57%, and
      digestive bleeding in 21%. The revealing manifestations were ascitis (75%),
      jaundice (71.7%), and hepatocellular carcinoma (42.3%). Higher risk for in
      hospital death (42.3%) was correlated with male gender, salaried employment, and
      presentation with jaundice, ascitis, or hepatocellular carcinoma. The risk of
      death during hospitalization was higher for patients who were of male gender,
      working as salaried employees and admitted for the first time with jaundice,
      ascitis, or hepatocellular carcinoma. CONCLUSION: A program for mass vaccination
      of children against hepatitis B virus is needed to prevent cirrhosis and
      hepatocellular carcinoma. A campaign against alcohol abuse could reduce cirrhosis
      due to alcohol consumption.

PMID- 22368938
TI  - [Distribution of Buruli ulcer in the Ze district of Benin].
AB  - The goals of this cross-sectional study conducted in the Ze district of Benin
      were to determine the overall distribution and prevalence of Buruli ulcer (BU)
      and to identify environmental and behavioral risk factors. A total of 425 current
      or previous BU patients from the study district were included. Data was obtained
      by direct observation, semi-structured interviews, and document review. The main
      findings can be summarized as follows. The overall prevalence of BU in the Ze
      district in 2006 was 52 cases per 10000 inhabitants. The prevalence of current
      and previous cases was 28.1 and 23.9 per 10 000 inhabitants respectively. The
      distribution of BU within the district was highly variable from one subdistrict
      to another and from one village to another within the same subdistrict. The
      subdistricts showing the highest and lowest endemicity were Djigbe with 265 cases
      per 10 000 inhabitants and Koundokpoe with 3 cases per 10 000 inhabitants
      respectively. Proximity of the hamlets to water bodies was a risk factor for the
      disease.

PMID- 22368939
TI  - [Perioperative cholangiography: a case study at Yaounde (Cameroon)].
AB  - For many years peroperative cholangiography has been routinely used for bile duct
      surgery in the Western countries. However recent publications showing high rate
      of inconclusive peroperative cholangiography (47%) has cast doubt on this
      attitude. Surgeons in Africa and particularly in Cameroon have already replaced
      peroperative cholangiography with other indicators such as clinical history and
      preoperative echography, anticipating cholangitis. For some indications, e.g.
      Mirizzi syndrome, peroperative cholangiography is essential for surgery. The
      fluoroscopes required for this exploration should be made available in our
      hospitals since they are also needed for traumatology, vascular surgery, and
      other specialities. In addition this syndrome may be more common in our region.

PMID- 22368940
TI  - [Citrobacter freundii spondylitis and sickle cell disease: a case in Morocco].
AB  - Infectious complications of sickle cell disease are common and can be serious and
      difficult to diagnose. Epidemiological aspects of these infections are well
      documented. The most common germ in children is pneumococcus followed by
      Haemophilus influenzae and minor salmonella. In adults gram-negative germs
      including minor salmonella are the most frequent. The purpose of this report is
      to describe a case of a Citrobacter freundii spondylitis with prevertebral
      abscess extending to dorsal and lumbar spinal areas. Diagnosis was made during
      work-up for persistent vaso-occlusive manifestations. Treatment consisted of
      percutaneous lumbar drainage associated with antibiotherapy.

PMID- 22368941
TI  - [Disseminated histoplasmosis caused by Histoplasma capsulatum in a renal
      transplant patient: first case report in the Reunion Island].
AB  - The purpose of this report is to describe the first case of indigenous
      disseminated histoplasmosis caused by Histoplasma capsulatum in a patient on
      immunosuppression 22 months after renal transplantation in the Reunion Island.
      Involvement was predominantly pulmonary and outcome was rapidly fatal. Diagnosis
      based on isolation of characteristic intramacrophagic Histoplasma capsulatum
      yeast cells from bronchoalveolar fluid was delayed since indigenous cases of this
      opportunistic infection were unprecedented. In addition to demonstrating the
      difficulty of achieving diagnosis in places located outside endemic areas without
      modern facilities, this case underlines the potentially the poor prognosis of
      disseminated histoplasmosis. This disease should be included in differential
      diagnosis in the Reunion Island where many patients undergo immunosuppresion and
      receive organs shipped in from outside locations.

PMID- 22368942
TI  - [Painful ophthalmoplegia in a woman from Burkina Faso: cerebral venous thrombosis
      (CVT) of the cavernous sinus].
AB  - Cerebral venous thrombosis (CVT) is a rare cerebral vascular pathology with
      highly variable clinical features and outcome. The purpose of this report is to
      describe a case of CVT of the cavernous sinus that presented as painful
      ophthalmoplegia. A 26-year-old woman with a contraceptive implant for seven
      months consulted at the Neurology Department of Yalgado Ouedrago hospital for a
      painful ophthalmoplegia that was initially diagnosed and treated as
      ophthalmoplegia migraine. One month later, clinical symptoms had progressed to
      asymmetric muscle weakness in all four limbs, right cerebellum ataxia and
      involvement of the trigeminal ophthalmic branch. Computerized axial tomography of
      the brain depicted a zone of unusual contrast extending from the cavernous sinus
      up to the tentorium cerebelli and a mass effect on the fourth ventricle. Analysis
      of the cerebrospinal fluid demonstrated a cellular reaction with 8 lymphocytes
      and high protein rate (0.64 g/L). The levels of C reactive protein (CRP) and D
      Dimeres were elevated: 16.6 mg/L and 0.99 microg/mL respectively. Based on a
      presumptive diagnosis of CVT, heparin treatment was undertaken and led to almost
      complete remission of the signs and symptoms. This case again shows the wide
      range of clinical features and outcomes of CVT that can oscillate between
      encephalitis, intracranial tumor or infection. As a result, CVT should be
      considered as a possible diagnosis in patients with focal neurological signs,
      intracranial hypertension syndrome, loss of consciousness or cavernous sinus
      syndrome whenever the context is right (post-partum, oestroprogestative,
      congenital thrombophilia).

PMID- 22368943
TI  - [Complicated sigmoid tumor: perforated amebiasis].
AB  - Amoeboma is an inflammatory mass of the colon. It can be an inaugural symptom and
      thus pose the problem of differential diagnosis with colon cancer. The purpose of
      this report is to describe the case of a 43-year-old patient who presented with
      acute abdomen. Physical examination revealed a perforated circumferential mass in
      the sigmoid colon. Based on a presumptive diagnosis of colonic cancer complicated
      by perforation, segmental colectomy was performed. Histological examination of
      the surgical specimen demonstrated colonic amoeboma. The patient was treated
      using metronidazole. Although rare, amoeboma must be considered in differential
      diagnosis of cancer of any colonic mass.

PMID- 22368944
TI  - [Profuse subcutaneous nodules in a Tunisian patient: Kaposi sarcoma revealing
      AIDS].
AB  - The purpose of this report is to describe a case involving Kaposi sarcoma as the
      inaugural manifestation of HIV infection at the full-blown AIDS stage. The
      patient was a 59-year-old Tunisian man who presented with profuse subcutaneous
      nodules and multiple lymph nodes. Treatment was based on antiretroviral therapy
      in association with radiotherapy.

PMID- 22368945
TI  - [Neuromeningeal cryptococcosis and AIDS: an 11-case series from Libreville,
      Gabon].
AB  - Neuromeningeal cryptococcosis occurs mainly in immunodepressed patients and
      especially AIDS patients. The purpose of this study was to determine the clinical
      and prognostic features of this severe brain infection. PATIENTS AND METHODS:
      This retrospective study was carried out on HIV-infected patients hospitalized
      for cryptococcal meningitis in the internal medicine unit of a military hospital
      in Libreville, Gabon from January 1, 2006 to November 31, 2009. RESULTS: Eleven
      cases of cryptococcosis were identified among a total of 290 cases of AIDS. Mean
      patient age was 39 years. The main clinical manifestation was headache that was
      either isolated or associated with other cerebral signs. In all cases,
      cerebrospinal fluid analysis demonstrated a clear aseptic aspect with direct
      examination after addition of India ink showing the presence of encapsulated
      yeast cells identified as cryptococcus. The patient was treated with amphotericin
      B and fluconazole. The mortality rate was 81.8% (9/11 cases). CONCLUSION: Since
      the manifestations of cryptococcosis during clinical AIDS are non-specific,
      systematic screening is recommended in AIDS patients. Early treatment could
      reduce mortality.

PMID- 22368946
TI  - [Weather and cholera: epidemic in Douala, Cameroon in 2004].
AB  - A cholera epidemic was recorded in Douala, Cameroon in 1971. Another 8-month
      outbreak occurred in January 2004 and spread in rapid succession to all health
      districts in Douala. The purpose of this study was to assess the association
      between meteorology and cholera incidence and preventive action in the health
      districts.

PMID- 22368947
TI  - [Pediatric upper gastrointestinal endoscopy: experience in a hospital setting in
      Cote d'Ivoire].
AB  - AIMS: The purpose of this report was to describe epidemiological aspects of
      endoscopic upper gastrointestinal endoscopy at a pediatric teaching hospital in
      Cocody, Cote d'Ivoire. MATERIALS AND METHODS: The records of all patients under
      15 years of age who underwent upper gastrointestinal endoscopy in the
      gastrointestinal endoscopy unit of a teaching hospital of Cocody between January
      1, 2000 and April 30, 2006 were reviewed. The following parameters were compiled:
      age, sex, indications, name of endoscopist, type of sedation, gastric biopsy to
      detect Helicobacter pylori, and endoscopic findings. RESULTS: Pediatric
      gastroscopy accounted for 1% of procedures performed in the upper
      gastrointestinal endoscopy unit. Patient ages ranged from 6 months to 15 years
      and M/F sex ratio was 0.88. The procedures were ordered by general practitioners
      in 55% of cases, gastroenterologists in 14%, and pediatricians in 10%. Sedation
      with intravenous midazolam 0.25 was used in 74% of patients (n = 38). No incident
      or complication was observed. Tolerance of the examination by the child was
      considered as poor by the operator in 96% of cases. The main indications for
      endoscopy were epigastralgia in 54% of cases, vomiting in 13.7%, and
      gastrointestinal bleeding in 13.7%. The procedure was performed or supervised by
      an operator with over ten years of experience in gastrointestinal endoscopy in
      55.1% and 54.0% of cases respectively. The main endoscopic finding was
      duodenogastric bile reflux in 23.5% of cases. Gastroscopy was normal in 43% of
      patients. Gastric biopsy to detect Helicobacter pylori was performed in 23% of
      patients. CONCLUSION: Pediatric gastroscopy performed under mild sedation by
      experienced endoscopists is a safe procedure for detecting lesions and obtaining
      biopsies for histological examination.

PMID- 22368948
TI  - [Value of genitography after late discovery of abnormal sexual development: 5
      cases in Lome, Togo].
AB  - The purpose of this report is to describe the value of genitography in management
      of abnormal sexual development abnormalities discovered at a late age (> or = 10
      years). Genitography was performed in 5 patients ranging from 10 to 23 years of
      age. No procedural difficulty was encountered in any of these patients.
      Genitography allowed correct determination of anatomical sex in all patients.

PMID- 22368949
TI  - [Arthropathic and degenerative pathology in rheumatology patients in Burkina
      Faso].
AB  - OBJECTIVE: The purpose of this report is to describe epidemiologic features of
      arthrosic and degenerative disorders observed during the first two years of
      rheumatologic practice in Ouagadougou, Burkina Faso. PATIENTS AND METHODS: The
      files of all patients examined between March 2006 to February 2008 were reviewed.
      All patients presenting arthrosic or degenerative disorders were included.
      RESULTS: Out of 1,439 patients examined during the study period, 1,078 (74.91%)
      were included. Spine pain accounted for 33.7% of cases, i.e., 485 patients
      including 306 with lumbago. The mean age in this group was 47.8 +/- 15.19 years
      and the M/F sex ratio was 0,75. Osteoarthritis represented 20.43% of cases
      including osteoarthritis of the knee in 18%. The mean age in this group was 54.66
      +/- 12.29 years and the M/F sex ratio was 0.23. Aseptic osteonecrosis (AON) of
      the femoral head was observed in 1.11% of cases, i.e. 16 patients including 8
      with sickle cell disease (SC) The mean age in this group was 40.75 years.
      Abarticular rheumatism accounted for 15.98% of cases, i.e. 230 patients including
      118 cases with tendinitis of the shoulder. The mean age in this group was 48.48
      years. CONCLUSION: Arthrosic and degenerative disorders observed in this series
      from Ouagadougou presented the same semiological features as in other African
      series. Primary osteoarthritis of the hip was uncommon.

PMID- 22368950
TI  - [Epidemiological features of multidrug resistant bacteria isolated from urine
      samples at the Mohammed V Military Teaching Hospital in Rabat, Morocco].
AB  - Hospital-acquired multidrug resistant bacteria infections are a serious public
      health issue causing increased morbidity, mortality and care cost. These risks
      underscore the need for health care institutions to maintain active panels to
      monitor, prevent, and manage hospital-acquired infections. The purpose of this
      study was to assess the epidemiology of urinary tract infection involving
      multidrug resistant bacteria at the Microbiology Laboratory of the Mohammed-V
      Military Teaching Hospital in Rabat. Study was carried out retrospectively on
      bacteria isolated from 10,243 urinary samples collected from January 1 to
      December 31, 2008. A total of 1,439 non-redundant bacteria (14.1%) meeting the
      criteria of urinary infection were identified. One hundred and three of the 1,439
      bacteria isolated (7%) were multidrug resistant. Multidrug-resistant bacteria
      were more common in in-patients (63.1%). Mean patient age was 53.8 +/- 18.2 and
      the M/F sex ratio was 2.2. The most common multi-drug resistant bacteria were
      Enterobacteria producing extended spectrum beta-lactamase (54.4% including 40.8%
      of Klebsiella pneumonia) and non-fermenting bacteria (45.6% including 26.2% of
      Pseudomonas aeruginosa. and 19.4% of Acinetobacter baumannii. These bacteria were
      resistant to the most commonly used antibiotics but remained highly sensitive to
      colistin, imipenem and amikacin.

PMID- 22368951
TI  - [Prevalence of diabetes mellitus in rural areas in Chad].
AB  - The purpose of this study conducted from January 10 to 28, 2004, was to determine
      the prevalence of diabetes mellitus in a sedentary rural population over the age
      of 18 years old in Chad. The study population included a total of 412 persons,
      i.e., 222 men (54%) and 190 women (46%), with a mean age of 35 years (range, 18
      to 90 years). Hypertension and obesity were observed in 16.4% and 8.7% of
      subjects respectively. The prevalence of diabetes mellitus was 7.39%. The
      prevalence of impaired fasting glucose (IFG) was 5.44% overall, 9% in women and
      2.77% in men (p < 0.0001). This study indicated a high prevelence of diabetes
      mellitus and female IGF in rural areas of Chad. Further study is needed to
      evaluate risk factors.

PMID- 22368952
TI  - [Hematological abnormalities associated with pulmonary tuberculosis in persons
      living with human immunodeficiency virus infection in Cote d'Ivoire].
AB  - The purpose of this study was to estimate the impact of HIV infection on
      hematological abnormalities detected during pulmonary tuberculosis in African
      adults. The charts of all patients over 14 years in whom diagnosis of pulmonary
      tuberculosis was confirmed by bacilloscopy and a hemogram was performed were
      reviewed. Thoracic radiography demonstrated unilateral and bilateral lesions. Two
      parallel mixed ELISA HIV tests were performed. A total of 98 patients with a mean
      age of 39 years were included in study. The male/female sex ratio was 0.88. HIV
      seroprevalence was 65%. Hemograms showed anemia in 95% of cases, leucopenia in
      20%, neutropenia in 35%, lymphopenia in 42%, and thrombopenia in 3%. No
      correlation was found with type of lung disease. Anemia (p = 0.001), leucopenia
      (p = 0.01) and thrombopenia (p = 0.001) were more extensive in HIV-infected
      patients. Hematological abnormalities were multiform. Cytopenia was the most
      frequent disorder and was positively correlated with HIV infection.

PMID- 22368953
TI  - Influence of variable precipitation on coastal water quality in southern
      California.
AB  - OBJECTIVES: To examine the consequences of changing precipitation levels on
      southern California's recreational coastal water quality, and compare the
      responses of watersheds with differing levels of urban development. METHODS: The
      geo-temporal relationship for six years (2000-2005) of precipitation levels,
      discharge rates for the ten primary waterways, and coastal water bacteria
      concentrations at seventy-eight southern California beaches were examined.
      RESULTS: Precipitation levels, river-creek discharge rates, and coastal water
      bacteria concentrations were significantly correlated (p < 0.01) for all ten
      watersheds investigated. Water bacteria concentrations significantly increased
      with higher levels of precipitation across 95% of the seventy-eight beaches
      investigated. A heavily developed watershed had significantly higher median
      bacteria concentrations (186 cfu) in the adjoining coastal waters compared to an
      undeveloped watershed (10 cfu) of similar size. CONCLUSIONS: Precipitation and
      ensuing runoff strongly control the rate of polluted water delivered to most
      beaches in southern California. Variable precipitation generates a greater
      response in coastal water bacteria concentrations in developed watersheds
      compared to undeveloped areas. Projected declines in regional precipitation as a
      consequence of climate change may result in less contaminated water delivered to
      coastal waters, thus decreasing risk of water associated illnesses during winter
      months.

PMID- 22368954
TI  - N2O emissions: modeling the effect of process configuration and diurnal loading
      patterns.
AB  - The objective of this research was to develop a mechanistic model for quantifying
      N2O emissions from activated sludge plants and demonstrate how this may be used
      to evaluate the effects of process configuration and diurnal loading patterns.
      The model describes the mechanistic link between the factors recognized to
      correlate positively with N2O emissions. The primary factors are the presence of
      ammonia and nitrite accumulation. Low dissolved oxygen concentrations also may be
      implicated through differential impacts on ammonia-oxidizing bacteria (AOB)
      versus nitrite-oxidizing bacteria (NOB) activity. Factors promoting N2O emissions
      at treatment plants are discussed below. The model was applied to data from
      laboratory and pilot-scale systems. From a practical standpoint, plant
      configuration (e.g., plug-flow versus complete-mix), influent loading patterns
      (and peak load), and certain operating strategies (e.g., handling of return
      streams) are all important in determining N2O emissions.

PMID- 22368955
TI  - Transformation of dissolved organic matter in a novel groundwater recharge system
      with reclaimed water.
AB  - A novel process, enhanced direct injection-well recharge system (EnDir), can
      overcome the technical difficulties during the application of conventional
      surface spreading and has been developed to recharge groundwater with reclaimed
      water. In this study, removal and transformation of dissolved organic matter
      (DOM) in the system were investigated in laboratory-scale experiments. Results
      demonstrated that dissolved organic carbon and trihalomethane formation potential
      values could be reduced from 6.54 +/- 1.30 mg/L and 267.9 +/- 24.3 microg/L to
      1.59 +/- 0.64 mg/L and 104.5 +/- 10.2 microg/L, respectively, as a result of DOM
      biodegradation in the aerobic short-term vadose soil treatment. Fluorescence
      spectra showed that aromatic protein-like substances and soluble microbial
      byproducts could be removed, to a great extent, in the soil system. Despite
      different removal efficiencies of DOM in different molecular weight fractions,
      the residual DOM was composed mainly of fulvic acid-like and humic acid-like
      substances, with molecular weights of 500 Da to 1 kDa.

PMID- 22368956
TI  - Biosorption of Pb(II) by biomass of KC-2: kinetic, equilibrium and characteristic
      studies.
AB  - Performance and characteristics of biosorption of Pb(II) had been studied in a
      batch system using the fungal strain biomass, KC-2. The biosorption performance
      was investigated by analysing the effects of such factors as the initial pH,
      initial Pb(II) concentration, and contact time at 303 K. The maximum Pb(II)
      adsorption was obtained at pH 5.0. The experimental data were described by the
      pseudo first-order, pseudo second-order and intraparticle diffusion kinetic
      models, and were closely followed the pseudo second-order kinetic model. The
      equilibrium experimental data were well fitted to Langmuir model and the maximum
      biosorption capacity was 84.03 mg g(-1). The adsorption mechanism was examined by
      FTIR, SEM and EDAX analysis. Results indicated that carboxylic, hydroxyl and
      amine groups were involved in the biosorption and ion exchange mechanism existed.

PMID- 22368957
TI  - Degradation of bisphenol A using UV and UV/H2O2 processes.
AB  - Bisphenol A (BPA; 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol) is a substance
      typically used in the plastic industry. It is used in the production of epoxy
      resins, polycarbonate, or fire retardants or as a stabilizer and an antioxidant
      in numerous types of plastics. Bisphenol A is introduced into the environment via
      municipal and industrial wastewater. Because of its hydrophobic properties, BPA
      has the potential for sorption on activated sludge during the biological
      wastewater treatment processes. This study investigated the degradation of BPA by
      means of UV-radiation and in the UV/H2O2 process with the presence and absence of
      hydrocarbonate ions (HCO3(-)) as hydroxyl radicals (OH*) scavengers. The
      calculated value of quantum yield was equal to 0.18, and the value of BPA rate
      constant with hydroxyl radicals was equal to 3.3 x 10(9) M(-1) s(-1).

PMID- 22368958
TI  - The population dynamics of nitrifiers in ammonium-rich systems.
AB  - Non-optimal pH, dissolved oxygen concentration, the presence of toxic substances,
      or the influence of grazers are known to cause disturbances in nitrification.
      Because activated sludge is a mixture of different organisms, bacteria, and
      higher organisms, the stability of processes such as carbon removal,
      nitrification, denitrification, and dephosphatation depends on a range of
      interactions. These interactions occur both between and within trophic levels.
      Understanding of the ecology of microorganisms involved in bioprocesses is
      essential for effective control of startup and operation of a particular process.
      The aim of the study was to gain further insight into the dynamics of nitrifiers
      in activated sludge at various sludge ages while treating higher concentrations
      of ammonium. The results confirmed the importance of Nitrosococcus mobilis and
      Nitrobacter sp. as the dominant nitrifiers responsible for nitritation and
      nitratation, respectively, in the presence of unlimited ammonium. The size of the
      dominant bacteria colony was larger compared to the other species present and
      reached 25 microm. Problems with nitrification occurred in all high-ammonium
      loaded reactors. The dynamics of nitrifier population was monitored by oxygen
      uptake rate (OUR) using a test enabling the OUR measurement separately for
      ammonium-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB). The
      results reveal the hypersensitivity of nitrifiers to the substrate and products
      of incomplete nitrification.

PMID- 22368959
TI  - Investigation of solution chemistry effects on sorption behavior of Cu(II) on ZSM
      5 zeolite.
AB  - The sorption of Cu(II) from an aqueous solution using ZSM-5 zeolite was
      investigated by batch technique under ambient conditions. Sorption was
      investigated as a function of pH, ionic strength, foreign ions, humic substances,
      and temperature. The results indicate that the sorption of Cu(II) on ZSM-5
      zeolite is strongly dependent on pH. Sorption is dependent on ionic strength at
      low pH, but independent of ionic strength at high pH values. The presence of
      humic/fluvic acid (HA/FA) enhances the sorption of Cu(II) on ZSM-5 zeolite at low
      pH values, and reduces Cu(II) sorption at high pH values. Sorption isotherms were
      well simulated by the Langmuir model. Thermodynamic parameters (i.e., deltaH0,
      deltaS0 and deltaG0) for the sorption of Cu(II) were determined from temperature
      dependent sorption isotherms at 293.15, 313.15, and 333.15 K, respectively.
      Results indicate that the sorption process of Cu(II) on ZSM-5 zeolite is
      spontaneous and endothermic.

PMID- 22368960
TI  - The relationship between mixed-liquor particle size and solids retention time in
      the activated sludge process.
AB  - Particle size distribution (PSD) analysis was used to evaluate the quality of
      mixed liquors collected from different activated sludge process modifications
      (i.e., conventional activated sludge, modified Ludzack-Ettinger, high-purity
      oxygen, step-anoxic, and oxidation ditch). An experiment protocol was developed
      to define the allowable sample holding time and provide representative and
      repeatable results. Samples of 26 treatment plants, with a total of 37 samples,
      were tested. A new indicator, called mean particle size (MPS), was introduced to
      describe the integrated mean particle size. The results of MPSs of three cut-off
      sizes (0.5 to 50, 100, and 200 microm) showed that the average size of mixed
      liquor biosolids increased with increasing solids retention time (SRT), and the
      number of particles in the sedimentation supernatant decreased with increasing
      SRT. Particle deflocculation occurred after excessive sample holding time, and
      analysis within 12 hours generally eliminated sample holding problems. The
      results provide a methodology using PSD for characterizing mixed-liquor
      biosolids.

PMID- 22368961
TI  - Seasonal performance of an outdoor constructed wetland for graywater treatment in
      a temperate climate.
AB  - The seasonal treatment efficiency of a pilot-scale constructed wetland system
      located outdoors in a semi-arid, temperate climate was evaluated for graywater in
      a comprehensive, 1-year study. The system consisted of two wetland beds in series
      -a free water surface bed followed by a subsurface flow bed. Water quality
      monitoring evaluated organics, solids, nutrients, microbials, and surfactants.
      The results showed that the wetland substantially reduced graywater constituents
      during fall, spring, and summer, including biochemical oxygen demand (BOD) (92%),
      total nitrogen (85%), total phosphorus (78%), total suspended solids (TSS) (73%),
      linear alkylbenzene sulfonate (LAS) surfactants (94%), and E. coli (1.7 orders of
      magnitude). Except for TSS, lower removals of graywater constituents were noted
      in winter--BOD (78%), total nitrogen (64%), total phosphorus (65%), LAS (87%),
      and E. coli (1.0 order), indicating that, although wetland treatment slowed
      during the winter, the system remained active, even when the average water
      temperature was 5.2 +/- 4.5 degrees C.

PMID- 22368962
TI  - Determination of the nitrous oxide emission potential of deammonification under
      anoxic conditions.
AB  - Various studies have been performed to determine nitrous oxide (N2O) emissions
      from conventional biological nitrogen removal processes in wastewater treatment
      like nitrification and denitrification in the main stream. However, with respect
      to the overall emissions of a wastewater treatment plant, part-stream treatment
      for high-strength wastewater (e.g., sludge liquor) is also expected to hold a
      significant emission potential because of high concentrations and extreme
      boundary conditions. This paper presents results from a laboratory-scale study on
      nitrous oxide production by biomass from a deammonification process (nitritation
      + anammox) under anoxic conditions. It was discovered that N2O formation results
      from incomplete endogenous denitrification rather than anammox and is dependent
      on substrate availability. Based on direct measurements of the dissolved N2O
      concentrations in a sequencing batch reactor, the dynamic behavior of N2O
      production is characterized in more detail. The results show that, during anoxic
      conditions, the N2O emission potential of deammonification is significantly lower
      than from conventional denitrification.

PMID- 22368963
TI  - Of: Characteristics of suspended solids, microorganisms, and chemical water
      quality in event-based stormwater runoff from an urban residential area, J. He,
      C. Valeo, A. Chu, N. F. Neumann, 82, 2333-2345 (2010).

PMID- 22368964
TI  - Pre-stroke use of statins on stroke outcome: a meta-analysis of observational
      studies.
AB  - BACKGROUND: Animal pre-clinical studies suggest that statins may have
      neuroprotective effects in acute ischaemic stroke. Statins might also increase
      the risk of developing haemorrhagic transformation after thrombolytic treatment.
      METHODS: We performed a systematic review and included studies that compared good
      functional outcome, defined as a modified Rankin Scale (mRS) score < or = 2 at 3
      months, in-hospital mortality and risk of symptomatic haemorrhagic
      transformation, between pre -stroke statin users and non users with acute
      ischaemic stroke. RESULTS: Eleven studies met our predefined inclusion criteria.
      Statin therapy before stroke-onset was associated with a lower risk of in
      hospital mortality (OR 0.56; 95% CI: 0.40 to 0.78, P < 0.0006). There was no
      difference between the two groups for good functional outcome at 3 months (OR
      1.01; 95% CI: 0.64 to 1.61, P = 0.96). Statin use was associated with an
      increased risk of developing symptomatic haemorrhagic transformation after
      thrombolytic therapy (OR 2.34; 95% CI 1.31 to 4.17, P = 0.004). CONCLUSIONS: Our
      meta-analysis suggests that pretreatment with statins does not improve 3 months
      functional outcome, defined as independence on mRS, but decreases in-hospital
      mortality and increases the risk of developing a symptomatic haemorrhagic
      transformation in patients treated with thrombolysis.

PMID- 22368965
TI  - Factors influencing therapeutic strategy for patients with basal ganglia
      hemorrhage--could age play a potential role in final treatment decision?
AB  - BACKGROUND: Hypertension-associated intracerebral hemorrhage, when compared with
      cerebral infarction and subarachnoid hemorrhage, is associated with worse
      clinical outcomes or major disability. Worse clinical outcomes have been observed
      in the elderly population though age as a factor influencing physicians' final
      treatment decision is not well determined. MATERIALS AND METHODS: We studied 199
      patients diagnosed with intracerebral hemorrhage (ICD code: ICD-9-CM-431) who
      visited a tertiary medical center from January 2003 to March 2006. Baseline
      characteristics, major medical histories (including co-morbidities), vital signs,
      neurological assessment (evaluated by the Glasgow Coma Scale), location of the
      hemorrhage, and the amount of hemorrhaging were all included as variables. A
      multivariate logistic regression model was chosen to evaluate the significant
      independent factors that could influence the physician's choice of treatment
      approach. RESULTS: There were totally 110 patients meeting the inclusion criteria
      for enrollment. We observed that worse neurological function on-arrival (chi2 =
      8.57, p = .01) and larger amount of bleeding (chi2 = 9.29, p = .01) were more
      likely to receive surgery. Multivariate logistic regression revealed that age,
      neurological function on-arrival, and the amount of hemorrhage were significant
      independent factors influencing the physicians' treatment decision (all p < .05).
      CONCLUSION: Age, after adjustment for clinical variables representative of
      clinical severity, was an important factor in the final therapeutic decision. Our
      data suggest that a comprehensive evaluation of the patients' on-arrival status
      may be made and that advanced age should not be a determining factor in the
      choice of final treatment methods.

PMID- 22368966
TI  - Depressive symptoms in patients admitted to a semi-intensive stroke unit.
AB  - Aim of this study was to evaluate depressive symptoms in a semi-intensive Stroke
      Unit (SI-SU) by a scale specifically devised to assess depression in patients
      with stroke and to identify the symptoms better contributing to the early
      detection of post stroke depression (PSD). Fifty-four patients admitted to a SI
      SU because of suffering from single, first-ever hemispheric stroke were enrolled.
      Depressive symptoms were assessed by the Post Stroke Depression Rating Scale
      (PSDRS). All patients were also evaluated by the National Institute of Health
      Stroke Scale (NIHSS), the modified Rankin scale, the Mini-Mental State
      Examination (MMSE) and the Frontal Assessment Battery (FAB). The PSDRS detected
      depressive symptoms in twenty-two patients (40%). The PSDRS scores were not
      influenced by severity of stroke, functional outcome, site of lesion and type of
      stroke. Three psychopathological factors were identified inside the PSDRS:
      "reactivity", "melancholic" and "apathetic", with significant inverse
      correlations with cognitive measures found only with the "apathetic" factor Less
      than one-half items of the PSDRS were able to identify overt depressive symptoms.
      Depressive symptoms are a frequent and early complication in patients referred to
      a SI-SU with the PSDRS being a suitable tool to detect depressive symptoms in
      acute phases of stroke.

PMID- 22368967
TI  - Prevalence of gluten sensitive enteropathy antibodies in restless legs syndrome.
AB  - The prevalence of restless legs syndrome (RLS) is increased in gluten sensitive
      enteropathy (GSE); but prevalence of GSE is not known in RLS. 96 RLS patients and
      97 healthy controls, both with or without iron deficiency were enrolled. All
      secondary RLS patients except iron deficiency were excluded. Subjects underwent a
      thorough biochemistry and routine blood analyses, and tissue transglutaminase
      antibodies (TTGA), endomysium antibodies (EMA) and gliadin antibodies (AGA) were
      also tested. In RLS patients positivity rates of all GSE antibodies were similar
      to those in controls. The rate of iron deficiency anaemia in RLS patients with at
      least one positive GSE antibody was significantly higher than that of RLS
      patients whose GSE antibodies were all negative. The prevalence of GSE antibodies
      in RLS patients is not increased. GSE might have a role in the aetiology of RLS
      in association with iron deficiency anaemia. Since the prevalence of GSE
      antibodies is not increased in RLS, it seems unlikely that GSE is involved in the
      aetiology of RLS through different mechanisms (e.g. immunological mechanisms)
      other than iron deficiency as proposed in some published papers.

PMID- 22368968
TI  - Long term outcome of lumbar discectomy: results from a biopsychosocial
      perspective.

PMID- 22368969
TI  - Influence of carvedilol on anticonvulsant effect of gabapentin.
AB  - The present study was performed to investigate whether or not carvedilol (a beta
      adrenoreceptor antagonist) potentiates the anticonvulsive activity of gabapentin
      against ICES (Increasing current electroshock) and PTZ (Pentylenetetrazole)
      induced seizures in mice. Further the effect of combination of both the drugs on
      spatial working memory and locomotor activity on rotarod was also evaluated. The
      biochemical estimation was done by measuring the lipid peroxidation and reduced
      glutathione in brain tissue. The results indicate that carvedilol significantly
      potentiates the anticonvulsive activity of gabapentin in both the models of
      epilepsy. The combination of both the drugs has no effect on spatial working
      memory and locomotor activity. In addition carvedilol in combination with
      gabapentin significantly decreased the level of the lipid peroxidation and
      increased the level of reduced glutathione (GSH) in brain. So, the present study
      showed that carvedilol potentiates the anticonvulsive activity of gabapentin,
      which can be useful for the treatment of epilepsy in patients with hypertension.

PMID- 22368970
TI  - Brain FDG-PET changes in ALS and ALS-FTD.
AB  - BACKGROUND: FDG-PET in ALS most typically demonstrates a primary (and sometimes
      also supplementary) motor cortex hypometabolism, often associated with more
      diffuse cortical hypometabolism involving mostly the dorsolateral prefrontal
      cortex, the medial and lateral premotor cortices, and the bilateral insular
      cortex involvement. In ALS-FTD, extensive temporal hypometabolism is seen in
      addition to severe diffuse frontal hypometabolism. METHODS: This study analyses
      FDG-PET findings in 6 ALS patients and 4 ALS-FTD patients. RESULTS: In addition
      to earlier described areas of hypometabolism in ALS, we found also reduced FDG
      PET metabolism in the medial frontal cortex, the orbitofrontal cortex, and the
      anterior temporal lobe in our ALS patients. The anterolateral area was the best
      preserved part of the frontal lobe in ALS patients. In ALS-FTD, frontal and
      temporal hypometabolism was severe (and parietal hypometabolism was often also
      present) with relatively preserved perirolandic metabolism. CONCLUSION: In ALS,
      more diffuse frontal and temporal FDG-PET hypometabolism was seen than earlier
      reported, with the anterolateral area as the best preserved part of the frontal
      lobe. In ALS-FTD, relatively preserved perirolandic metabolism was seen,
      associated with severe frontal and temporal hypometabolism.

PMID- 22368971
TI  - Surgical management of focal cortical dysplasia.
AB  - Focal cortical dysplasia is a malformation caused by abnormalities of cortical
      development. It is characterized by no dysmorphic or ballon cells (type I),
      dysmorphic neurons witout or with ballon cells (type II). It is the main cause of
      pharmacoresistant epilepsy. The combination of clinical and neurophysiological
      findings provided by VEEG and MRI had lead to an improvement in the diagnosis and
      outcome of FCD. This paper describes our experience in the form of a
      retrospective study conducted on the patients affected by FCD who were treated in
      the Clinical Neurophysiology Service at University Hospital of Lille in France.

PMID- 22368972
TI  - The effects of timing of aneurysm surgery on vasospasm and mortality in patients
      with subarachnoid hemorrhage.
AB  - OBJECTIVE: The purpose of the present study was to compare the effects of early
      and late surgery on postoperative vasospasm and mortality in patients with
      subarachnoid hemorrhage (SAH). METHODS: The data of patients with SAH who
      underwent aneurysmal clipping at the Kartal Training and Research Hospital
      between 1999 and 2005 were retrospectively analyzed. The patients who underwent
      early (0-3 days) and late surgery (> or = 4 days) were evaluated as two groups.
      Patient outcomes were assessed 1 month after surgery. RESULTS: Of 159 patients
      (mean age, 49 years; 71 males) with SAHs, 135 (mean age, 51 years; 55 males)
      underwent early surgery and 24 patients (mean age, 56 years; 16 males) underwent
      late surgery. The overall postoperative vasospasm rate was 10.7%. The rate of
      postoperative vasospasm was significantly higher in the late surgery group
      (41.7%) compared to the early surgery group (5.2%; p < 0.001). There were 15 post
      operative deaths (9.4%). The mortality rate in the late surgery group (25.0%) was
      significantly higher than the early surgery group (6.7%; p = 0.005). CONCLUSIONS:
      The present study has demonstrated that early surgery is advantageous over late
      surgery in patients with SAH with lower post-operative vasospasm and mortality
      rates.

PMID- 22368973
TI  - Dopamine-deficiency-enhanced hyperthermia and rhabdomyolysis during a heat wave
      in a metachromatic leucodystrophy heterozygote with metabolic myopathy.
AB  - Whether a dopamine-deficiency syndrome in a Parkinson-syndrome (PS) may occur
      more easily during a heat wave than during more temperate climate conditions is
      unknown. We report a case that may suggest this. A 56 yo male with heterozygosity
      for metachromatic leucodystrophy and a history of metabolic myopathy, PS and
      diabetes experienced worsening of the PS during a heat wave. His condition
      further deteriorated upon reduction of ropinirol, resulting in hyperthermia,
      respiratory insufficiency, rhabdomyolysis, and severe thrombocytopenia. One month
      later he was alert but tetraplegic and required ventilatory support. Hyper-CK
      emia returned to similar levels as before rhabdomyolysis. Reduction of dopamine
      agonists during a heat wave may induce a dopamine deficiency syndrome with
      hyperthermia, rhabdomyolysis and thrombocytopenia.

PMID- 22368974
TI  - Rapidly progressive subacute sclerosing panencephalitis presenting with acute
      loss of vision.
AB  - A 10-year-old male presented with vision loss and behavioral changes. He had
      midpoint pupils with no reaction to light and normal funduscopic examination.
      Cranial magnetic resonance imaging revealed bilateral cortical lesions at parieto
      occipital lobes. Elevated measles antibody titers in the cerebrospinal fluid
      confirmed the diagnosis of subacute sclerosing panencephalitis. Despite oral
      inosiplex and supportive care, patient developed generalized seizures with
      frequent myoclonic jerks and rapidly progressed into coma. Cortical blindness in
      subacute sclerosing panencephalitis can be an early indicator for fulminant
      course.

PMID- 22368976
TI  - Acute shoulder-girdle neuralgic amyotrophy (Parsonage-Turner syndrome with
      saphenous nerve involvement.
AB  - Parsonage-Turner syndrome (PTS) is a relatively rare cause of upper extremity
      weakness and pain. There is currently no effective treatment for PTS although
      corticosteroids are recommended. Here we report the case of a man with acute PTS
      and exceptional involvement of both saphenous nerves, advantageously treated with
      intravenous immunoglobulin.

PMID- 22368975
TI  - Rett syndrome associated with continuous spikes and waves during sleep.
AB  - Major speech impairment is a cardinal feature of Rett syndrome. Epilepsy, of
      variable presentation, is also frequently described. We report a girl who
      presented rapid speech regression while EEG showed continuous spikes and waves
      during slow sleep. The clinical picture was consistent with Rett syndrome,
      confirmed by MECP2 mutation R133C. We hypothesized that speech regression was
      partially related to nocturnal epileptic activity. Several antiepileptic drugs
      were used unsuccessfully but valproic acid was accompanied by improvement of
      verbal fluency, social interaction and manual abilities as measured by the Quebec
      Scale of Adaptive Behaviors and the Rett syndrome adapted Kerr scale. Continuous
      spikes and waves during slow sleep are unexpected in the early stages of Rett
      syndrome. This report suggests that it might contribute to the clinical
      impairment, in particular communicative capabilities, and that adequate
      antiepileptic treatment may be beneficial.

PMID- 22368977
TI  - Neoplastic meningitis: a rare presentation of bronchial adenocarcinoma.
AB  - Following chronic daily headache, neoplastic meningitis was diagnosed in a non
      smoking 44-year-old man. A bronchial adenocarcinoma was found to be the primary
      tumor. He was treated with erlotinib. Meningitis as the first manifestation of a
      malignancy is very rare.

PMID- 22368978
TI  - Coexistence of ankylosing spondylitis and multiple sclerosis.
AB  - Ankylosing spondylitis is reported to involve not only the joints but neurologic
      systems as well. The association of MS and AS has rarely been reported in the
      literature and epidemiological studies did not prove a definite relationship
      between these two conditions at present. We here describe a HLA-B 27 positive AS
      patient with MS symptoms and review the literature on the association of two
      diseases.

PMID- 22368979
TI  - Case report: imaging findings in a "butterfly" vertebra.
AB  - A "butterfly" vertebra is a rare congenital anomaly, presenting as a sagittal
      cleft in the vertebral body. In the literature it has been described as an
      isolated finding, but it can also be associated with various syndromes, such as
      Alagille, Jarcho-Levin, Crouzon and Pfeiffer syndrome. We present a case of a 35
      year old man with chronic low back pain. The diagnosis of a butterfly vertebra of
      S1 with disc space narrowing of L5-S1 was made. Usually the abnormality occurs at
      the thoracolumbar spine and we are not aware of a description of a sacral
      butterfly vertebra. Although a butterfly vertebra is usually asymptomatic, it
      could lead to discal herniation or chronic back pain due to alteration in spinal
      biomechanics.

PMID- 22368980
TI  - Subacute gestational neuropathy: role of thiamine deficiency.

PMID- 22368981
TI  - Supratentorial intraventricular hemangioblastomas.
AB  - A 33-year-old male presented with a headache. He had a history of a previous
      surgical procedure for excisions of cervical spine hemangioblastomas 13 years
      prior He had a family history of von-Hippel Lindau (VHL) disease, and a VHL
      mutation was identified. Brain magnetic resonance imaging showed enhanced mass
      lesions in both the third and right lateral ventricles as well as in the
      cerebellum. The lesion in the right lateral ventricle also had a cystic
      component. Two-staged resections of the tumors in the third and right lateral
      ventricles and ventriculo-peritoneal shunt were performed. A histopathological
      specimen was compatible with a hemangioblastoma. Supratentorial intraventricular
      hemangioblastomas are extremely rare. We reviewed the literature and discussed
      the features.

PMID- 22368982
TI  - A patient with superficial siderosis, intraspinal cyst, low-pressure headache and
      low-lying cord.
AB  - Superficial siderosis is a rare condition caused by deposition of hemosiderin in
      the central nervous system. In recent years, it has been used to identify dural
      defects connecting the intrathecal space with the intraspinal fluid-filled
      collection seen in patients with superficial siderosis. However rare reports
      describe the association of low-lying cord in superficial siderosis patients. We
      present a patient with progressive cerebellar ataxia, sensorineural hearing loss,
      low-pressure headache, pyramidal signs and additional cervical and lumbar
      radiculopathy with neurogenic bladder which might be related to cervical disc
      herniation and tethered cord. CSF and Magnetic resonance imaging (MRI) studies
      confirmed the diagnosis of superficial siderosis. Dural defect is indirectly
      suspected by existence of fluid-filled collection ventral to the spinal cord and
      low-pressure headache in our patient. Underlying causes of low-pressure headache
      and possible dural defect should be searched for as an associated and possibly
      treatable condition in superficial siderosis and provide further insights into
      the mechanism of bleeding in our patient who have an intraspinal fluid-filled
      collection.

PMID- 22368983
TI  - Isolated lingual dystonia induced by speaking: a rare form of focal dystonia.
AB  - Focal lingual dystonia is a rare condition that can be misdiagnosed as a
      psychogenic problem because it may interfere with chewing, swallowing, and
      speaking. We present a patient with an uncommon type of dystonia (speech-induced
      primary lingual dystonia), that responded well to botulinum toxin injection.

PMID- 22368984
TI  - Acute lymphoblastic leukemia presenting with oculomotor nerve palsy.
AB  - A 48-year-old man presented with left ptosis and double vision. Laboratory test
      findings indicated acute lymphoblastic leukemia (ALL). Lymphoblastic infiltration
      of both cavernous sinuses was observed on pituitary gland magnetic resonance
      imaging. Leukemias may present by many clinical conditions, but isolated cranial
      nerve palsy is very rare. To our knowledge, this is the first case of ALL
      presenting with oculomotor nerve palsy. Clinicians should consider oculomotor
      nerve palsy as the first ALL indication.

PMID- 22368985
TI  - Internal decompressive craniectomy with craniotomy: a novel surgical therapy of
      giant frontal mucocele complicated by subdural empyema.
AB  - INTRODUCTION: Giant frontal mucocele (GFM) is an extremely rare cause of frontal
      lobe syndrome. Subdural empyema (SDE) is an uncommon complication of paranasal
      sinisutis, for which craniotomy and decompressive craniotomy are the most
      effective surgical procedures. CASE REPORT: A 54-year-old man was brought
      unconscious to the Emergency Room where recurrent generalized seizures occurred.
      Heroine abuse, HCV related hepatitis, prolonged antibiotic therapy for treatment
      of purulent rhinorrhea, along with recent personality changes, was reported. High
      white blood cell count, pansinusitis, GFM, SDE and cerebritis were documented.
      The patient underwent bifrontal craniotomy in emergency, extensive drilling of
      the inner aspect of the frontal bone, surgical toilette of the enlarged frontal
      sinus and its "cranialization". Prevotella intermedia and Fusobacterium nucleatum
      were isolated and antibiotic therapy was started intravenously and then continued
      orally for three months. Two years later the patient has recovered, though minor
      signs of frontal lobe syndrome persist. DISCUSSION: To the Authors knowledge this
      is the first case of GFM with SDE reported in the literature. Although
      decompressive craniectomy is advocated in extreme conditions, as in this case,
      "internal decompressive craniectomy", obtained with craniotomy and cranialization
      of the frontal sinuses, is strongly advocated in cases of SDE associated with
      megasinuses.

PMID- 22368986
TI  - Vestibular evoked myogenic potentials in vestibular neuronitis.

PMID- 22368987
TI  - Decompensated chronic congenital hydrocephalus.

PMID- 22368988
TI  - Imaging findings of familial dementia with a tau R406W mutation.

PMID- 22368989
TI  - Basilar artery dissection.

PMID- 22368990
TI  - Unusual gyriform tumor of the posterior fossa in a child.

PMID- 22368992
TI  - Usefulness of serum glial fibrillary acidic protein for the diagnosis of
      glioblastoma with a dural tail sign.

PMID- 22368991
TI  - Resolution of abnormal fractional anisotropy of substantia nigra in
      organophosphate intoxication.

PMID- 22368993
TI  - [Basic principles in treatment of spinal cord injuries].

PMID- 22368994
TI  - Education of medical students in Bitola on tobacco use and their role in health
      promotion activities.
AB  - Health professionals should have a key role in health promotion activities
      regarding reduced tobacco use. This study was aimed at presenting students' level
      of knowledge on harmful effects of smoking and the level of training they had
      gained in order to quit smoking. The research was done as an epidemiological,
      cross sectional study according to the standardized methodology of Global Health
      Professional Survey. The study sample consisted of a hundred college students.
      During the educational process, 77.5% of females, and 93.1% of males were
      educated on harmful and dangerous effects of smoking and 59.2% of females and
      62.1% of males were instructed how to give up smoking and the age of 86.6% of
      them was from 18 to 24 years. It has been concluded that some qualitative changes
      are needed in the current curricula and syllabi.

PMID- 22368995
TI  - Incidence of amiodarone-induced thyroid dysfunction and predictive factors for
      their occurrence.
AB  - Amiodarone treatment is associated with the occurrence of thyroid dysfunction.
      The aim was to determine the incidence of amiodarone-induced thyroid dysfunctions
      and the influence of gender, age, treatment duration, goiter, thyroid antibodies,
      thyroid echogenicity and family history on their appearance. Of 248 consecutive
      patients, 144 males and 104 females, referred to thyroid status screening, 16%
      were with clinical dysfunction, 21% with sub-clinical dysfunction and 63% were
      euthyroid. The presence of goiter and thyroid peroxidase antibodies were the
      significant individual predictive factors for the occurrence of clinical
      dysfunction, and in the multivariate regression model, the presence of goiter was
      a significant predictive factor with the prognostic value of 80%. For sub
      clinical dysfunction, the significant individual predictive factors were female
      gender and the presence of goiter, as well as in the multivariate regression
      model, with the prognostic value of 74.5% for female gender and 77.5 % for the
      presence of goiter. It is necessary to check the thyroid status both before and
      during amiodarone treatment. Administration of other anti-arrhythmic drugs and/or
      more frequent check-ups of the thyroid status should be taken into consideration
      in patients at higher risk, i.e. women with positive thyroid peroxidase
      antibodies and goiter.

PMID- 22368996
TI  - [Analysis of the shoulder joint mobility in overhead sports before and after
      experimental treatment].
AB  - INTRODUCTION: "Overhead" sports, characterized by predominant movements of the
      hands above the head, are associated with very dynamic, often acyclic movements
      and require strong muscles of humero-scapular regions with high mobility of the
      shoulder joint as well as flexibility and ability to relax these muscles. This
      study was aimed at analyzing the shoulder joint mobility before and after
      conducting kinesiology treatment for a period of 6 months. The research included
      two complex exercises. MATERIAL AND METHODS: The study included 100 "overhead"
      sports male athletes, who were randomly divided into the experimental and control
      group, aged 14 to 18 years. The range of motion was measured in degrees by
      goniometer. We calculated the central and depression parameter. RESULTS: There
      was a statistically significant difference inflexion, extension, abduction,
      adduction, external and internal rotation at the final measure in favor of the
      experimental group at the level of significance p<0.001, and some positive
      effects of the applied exercises were observed. DISCUSSION: Kinesitherapy had
      positive effects on the elasticity of the connective tissue capsule, ligaments
      and tendons. Changes in the shoulder area f the "overhead" sports athletes can be
      reduced to the same extent and at the same time by stretching and strength
      exercises. CONCLUSION: The authors of this paper have given their modest
      contribution by suggesting a more appropriate planning of training and
      performance of players at training and matches. This paper tries to emphasize the
      importance of proper incorporation of the corrective exercises in training.

PMID- 22368997
TI  - [Impact of work place stresses on work ability index in patients with depressive
      disorders].
AB  - INTRODUCTION: Depression seriously affects one's ability to perform work tasks
      and function at work. We studied the impact of both the individual and work
      factors on work ability index in patients suffering from depression. MATERIAL AND
      METHODS: The prospective study, which was conducted by using questionnaires,
      included 210 patients with depression, who had been on sick leave from 60 to 360
      days. The individual factors were evaluated by the standardized abridged form of
      Occupational Stress Questionnaire, while the work place factors in relation to
      work ability were evaluated by the work ability index. RESULTS: Poor work ability
      was observed in 151 (71%) of subjects suffering from depression. All workplace
      stresses, lack of support by colleagues and supervisors, ergonomically not
      adjusted work and huge work load are statistically associated with poor work
      ability index (P=0.001). More than 95% of variables of the evaluated work ability
      index are the result of varying in the group of stresses at work place (R2=0.95).
      Perception of bad health condition (Rsq=0.412, P=0.001), low level of life
      satisfaction (Rsq=0.309, P=0.001), low level of motivation and work knowledge
      (Rsq=0.309, P=0.001) are predictors for poor work ability. The work ability
      cannot be related with age and sex. CONCLUSION: The key activities for
      maintaining the work ability at the times when epidemic of depression emerges, as
      it is nowadays, are timely carrying out the psycho-treatments, mental and
      professional rehabilitation, occupational therapy and adapted work place.

PMID- 22368998
TI  - [Influence of glucose homeostasis on maturation and ontogenesis of fetus].
AB  - INTRODUCTION: The aim of the paper is to examine the incidence and the rate of
      cardio respiratory disorders in mothers of newborns with diabetes mellitus in
      pregnancy as well as their influence on the perinatal outcome. MATERIAL AND
      METHODS: A prospective and random study included 102 newborns, 31 newborns of
      mothers with glucose homeostasis disorder (group I) and 71 newborns of healthy
      mothers (group II). The average age, body height, body weight, body mass index,
      parity and illness duration of the pregnant women were recorded as well as the
      delivery method Every newborn underwent physical examination in order to
      determine the Apgar score, body weight and length. Electrocardiogram, brain
      ultrasound and the basic hematology biochemical and microbiological analysis were
      done as well. RESULTS: The average weight and obesity incidence were higher in
      diabetic women than in the control group and their newborns were heavier and of
      lower gestational age. Heart failures were diagnosed in 5 (1612%) newborns of
      diabetic mothers and in 1 (1.4%) of a healthy pregnant woman (p<0.01).
      Respiratory disorders were diagnosed in 48.4% of newborns of diabetic mothers and
      12.64% of healthy mothers (p<0.01). Additional oxygen was needed by 42% of
      newborns of diabetic mothers and 19.7% of newborns of healthy mothers.
      CONCLUSION: Congenital anomalies of cardiovascular system and respiratory
      disorders were 6-8 times more frequent in newborns of diabetic mothers than in
      newborns of healthy mothers.

PMID- 22368999
TI  - [Place and role of von Willebrand factor in acute coronary syndromes].
AB  - INTRODUCTION: Advanced understanding of the pathophysiology of ACS has led to the
      marked increase in development of biomarkers for diagnosis, risk stratification,
      therapeutic decision-making, and assessment of clinical outcomes, but there is
      still a need for a marker that could verify or exclude the existence of acute
      coronary syndrome as early as possible. The aim of our study was to assess the
      value of von Willebrand factor as a potential marker of heart necrosis in early
      diagnosis of acute coronary syndrome. MATERIAL AND METHODS: One hundred fifteen
      patients were taken a blood sample on the first day after being diagnosed to have
      an acute coronary syndrome in order to determine the values of their von
      Willebrand factor antigen and von Willebrand factor activity. RESULTS AND
      DISCUSSION: The results of the study clearly showed that patients had
      significantly elevated both these parameters compared to the reference values and
      controls, and that von Willebrand factor represented a highly sensitive and
      specific marker which correlated with the degree of necrosis and clinical
      picture. CONCLUSION: These results should be confirmed by further multi-center
      investigations performed on a higher number of participants.

PMID- 22369000
TI  - [Biology and intracellular life of chlamydia].
AB  - INTRODUCTION: Chlamydiae are Gram-negative obligate intracellular bacteria. The
      developmental cycle of Chlamydiae is specific and different from other bacteria.
      The elementary body is the infectious form of the organism, responsible for
      attaching to the target host cell and promoting its entry. The reticulate body is
      the larger, metabolically active form of the organism, synthesizing
      deoxyribonucleic acid, ribonucleic acid and proteins. The elementary body and
      reticulate body represent evolutionary adaptations to extracellular and
      intracellular environments. INTRACELLULAR PERSISTENCE OF CHLAMYDIA:
      Predisposition of Chlamydia to persist within the host cell has been recognized
      as a major factor in the pathogenesis of chlamydial disease. The persistence
      implies a long-term association between chlamydiae and their host cell that may
      not manifest as clinically recognizable disease. The ability of chlamydia to
      remain within one morphological state for a long time in response to exogenous
      factors suggests an innate ability of these organisms to persist intracellulary
      in a unique developmental form. Chlamydiae induce interferon gamma and exhibit
      growth inhibition in their presence. While the high levels of interferon gamma
      completely restrict the development of chlamydia, its low levels induce the
      development of morphologically aberrant intracellular forms. The persistent forms
      contain reduced levels of major outer membrane protein but high levels of
      chlamydial heat shock protein. CONCLUSION: Immunopathogenesis of chlamydial
      infection is one of the main focal points of current research into Chlamydia.
      Chlamydial infections are highly prevalent, usually asymptomatic and associated
      with serious sequelae. Screening programmes are the most important in the
      prevention of a long-term sequele.

PMID- 22369001
TI  - [Results and experiences after 1000 IVF cycles at the Clinic for Gynecology and
      Obstetrics in Novi Sad].
AB  - INTRODUCTION: Infertility affects 15-17% of reproductive age couples in our
      country, and 10-15% of couples worldwide. The aim of this paper was to present
      results and experience gained after the first 1000 cycles of the national In
      Vitro Fertilization (IVF) program, to offer professional standard of work in our
      country and to compare it with results obtained in Europe and worldwide. MATERIAL
      AND METHODS: The study prospectively included 1000 women who had undergone
      national In Vitro Fertilization program from October 2006 until November 2009 at
      the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi
      Sad. RESULTS: The analysis included 1000 in vitro fertilization cycles. Male
      factor infertility was the leading cause (56.9%) followed by tubal factor
      (45.9%). The classic method of in vitro fertilization constituted 72.3% of all
      cycles, while intracytoplasmic sperm injection (ICSI) method was used in 27.7% of
      all cycles. The average number of embryos transferred was 2.67. The cycle
      cancellation rate was 14.10% and the aspiration rate was 94.40%. The clinical
      pregnancy and live birth rate were 33.41% and 26.78% per embryo transfer
      respectively. DISCUSSION AND CONCLUSION: The results in our study showed that in
      our setting there are far less intracytoplasmic sperm injection cycles compared
      with the European average of 66.5% of all fresh cycles, and that we transferred
      more embryos on average. Our success rates are comparable with those in other
      European countries where the clinical pregnancy rates per aspiration and per
      transfer for in vitro fertilization were 29 and 32.4%, respectively in the period
      of observation. For intracytoplasmic sperm injection, the corresponding rates
      were 29.9 and 33%.

PMID- 22369002
TI  - [Epidemiological characteristics of hepatitis A in Vojvodina from 1988 to 2009].
AB  - INTRODUCTION: Hepatitis A represents a significant epidemiological problem in
      many regions of the world. This research was aimed at analyzing trends and
      distribution of hepatitis A in the Autonomous Province of Vojvodina in Serbia.
      MATERIAL AND METHODS: The authors used data on individual cases and outbreak
      reports in the period from 1988 to 2009 obtained from the Registry of
      Communicable Diseases kept at the Center for Disease Control and Prevention,
      Institute of Public Health of Vojvodina. RESULTS: The total of 10.471 cases was
      recorded with average incidence of 23.4/100.000 and with a decreasing trend. This
      disease occurs as an endemoepidemic with a cyclic increase in the incidence in
      time intervals of 3, 4 and 6 years. The disease has seasonal character and is
      most frequently observed in autumn and winter with the highest percentage of
      cases in October-November after the beginning of school year and forming of
      school collectives. The age-specific incidence is highest in school age children
      due to agglomeration of susceptible population. During the observed period, the
      total of 160 outbreaks was recorded with over 5,000 reported cases. The highest
      number of outbreaks was recorded in school collectives and then in peri-urban
      settlements with poor hygiene. Two outbreaks occurred at institutions for people
      with special needs. Outbreaks were progressive in course and contact was the
      dominant mode of transmission. CONCLUSION: Although hepatitis A incidence trend
      is decreasing, this disease still has endemoepidemic character of occurrence.
      Such an epidemiological situation is most probably caused by slow and limited
      impact of hygienic measures. A significant contribution to further incidence
      reduction could be achieved by active immunization.

PMID- 22369003
TI  - A case series of 22 patients with internal carotid artery dissection.
AB  - The aim of this study was to analyze the spectrum of clinical presentations of
      internal carotid artery dissection. Twenty-two patients with internal carotid
      artery dissection, mean age 39.02, were evaluated over the past ten years.
      Magnetic resonance imaging and magnetic resonance angiography were used to
      establish the diagnosis. Facial and neck pain and Horner's syndrome were the only
      presenting symptoms in 4 patients (without brain infarction); facial pain,
      Horner's syndrome and contralateral sensorimotor deficit in 6; headache and
      contralateral sensorimotor deficit in 2; contralateral sensorimotor deficit with
      or without speech impairment in 10. Internal carotid artery dissection was
      triggered by a trauma in 7, whereas it was spontaneous in 15. Magnetic resonance
      imaging revealed infarction in 18 patients. A good outcome (modified Rankin score
      0-2) was seen in 20 patients. The spectrum of clinical presentations of internal
      carotid artery dissection is variable. Internal carotid artery dissection is not
      necessarily accompanied by infarction on magnetic resonance imaging.

PMID- 22369004
TI  - [Morbidity and mortality of patients suffering from gestational trophoblastic
      diseases at the Clinic of Gynecology and Obstetrics, Clinical Center of Serbia in
      the period from 2000 to 2007].
AB  - INTRODUCTION: Gestational trophoblastic disease is a heterogenous group of
      diseases with malignant potential. The aim of this retrospective study was to
      evaluate potential risk factors in pathogenesis of gestational trophoblastic
      disease, its morbidity and mortality as well as treatment results. METHOD: We
      investigated 82 patients who were treated at the University Clinic of Gynecology
      and Obstetrics Clinical Center of Serbia from Jan 1st 2000 to Dec 31st 2007. The
      data were collected from their hospital charts and referred to gynecological
      anamnesis, diagnosis, protocols of operated patients, diagnosis,
      histopathological findings, decisions of expert team for trophoblastic disease
      and hospital discharge. RESULTS: The incidence was 1.5 per 1000 deliveries. The
      most frequent finding was hydatiform mole (59.8%). The patients were treated by
      chemotherapy and surgery. All patients survived. CONCLUSION: The maternal age and
      a larger number deliveries and abortions are risk factor for gestational
      trophoblastic disease. The incidence in our clinic is approximately equal to the
      incidence in western countries in this period.

PMID- 22369005
TI  - [Carbapenems resistance of Acinetobacter spp strains isolated from wound swabs
      during 2009-2010].
AB  - INTRODUCTION: Acinetobacter spp has become an important cause of nosocomial
      infections due to its great ability to survive and spread in a hospital setting
      and to develop resistance to many antibiotics. The aim of this study was to
      examine the resistance to carbapenems and other commonly used antibiotics in
      strains of Acinetobacter isolated from wound swabs. MATERIAL AND METHODS: In the
      Laboratories of Microbiology Center at the Institute for Public Health in Novi
      Sad wound swabs were taken from the patients hospitalized at the Institutes and
      Departments of the Clinical Center of Vojvodina in Novi Sad. A total of 271
      Acinetobacter spp strains were tested to susceptibility on carbapenems and other
      most commonly used antibiotics by disk diffusion method according to the
      recommendation of the Clinical and Laboratory Standards Institute. RESULTS AND
      DISCUSSION: Acinetobacter spp (271 isolates) developed resistance to imipenem and
      meropenem (67.4% and 64.4%). The resistance to both cephalosporins III and IV
      generation and ciprofloxacin was 100%. The resistance to ampicillin-sulbactam was
      71.4%. CONCLUSION: Our results show high resistance to carbapenems in
      Acinetobacter spp strains isolated from wound swabs. These facts suggest the need
      for continuous monitoring of susceptibility in order to take adequate measures to
      prevent and control spreading of resistant strains.

PMID- 22369006
TI  - [Treatment of cervical cancer in the Republic of Srpska].
AB  - INTRODUCTION: Since 1897, when the first radical hysterectomy with
      lymphadenectomy was done by Wertheim in Vienna, this operation has had the
      central role in the surgical treatment of invasive cervical tumors. MATERIAL AND
      METHODS: In the period from 1997 to 2010, 177 patients diagnosed with invasive
      cervical cancer according to the International Federation of Gynecology and
      Obstetrics (FIGO) stage IB1 - II were operated at the Department of Obstetrics
      and Gynecology in Banja Luka. All patients underwent radical hysterectomy by
      Wertheim - Meigs. The aim of this study is to present the technique of this
      operation, as well as its effectiveness in the treatment of cervical cancer.
      RESULTS: The distribution of the patients having invasive cervical cancer
      according to the International Federation of Gynecology and Obstetrics
      classification was as follows: I B1 - 35.67%, I B2 - 23.17%, II A - 15.48%, II B 
      25.68% on average is 21.3 removed lymph glands. The rate of intraoperative and
      postoperative complications was 8 (4.51%) and 17 (9.60%), respectively. Of the 26
      patients who were operated in the period from 2005 - 2010, 13 had stage II B
      according to the International Federation of Gynecology and Obstetrics; there
      were 6 lethal outcomes (23.08) and the five-year survival rate was 76.92%.
      DISCUSSION AND CONCLUSION: By applying the proper surgical technique and early
      prevention of immediate complications, we achieved satisfactory results in
      operative morbity and mortality, intraoperative and postoperative complications
      of the lesion for radical surgery by the Wertheim-Meigs-in the treatment of
      cancer of the uterus in the I B - II B stage according to the International
      Federation of Gynecology and Obstetrics classification.

PMID- 22369007
TI  - Heterotopic ossification following surgical treatment of avulsion fracture of the
      anterior inferior iliac spine.
AB  - Avulsion fractures of the anterior inferior iliac spine are rare injuries of the
      pelvic ring and occur during sports activities. Hereby is presented a case of a
      22-year-old professional football player who was diagnosed to have an avulsion
      fracture of the anterior inferior iliac spine on the right side four months after
      the initial injury and he was treated surgically with the excision of the avulsed
      fragment. The football player recovered completely and returned to his usual
      sports activities. Two years later, due to the pain in the hip an x-ray and MR
      image were made, which established the existence of crescent formation, a
      heterotopic bone, in the area of the anterior inferior iliac spine, which was
      surgically removed. Physical and medical therapy was conducted and after four
      months, the professional athlete was back playing football. Two years after the
      surgical excision of heterotopic ossification, the patient was completely
      asymptomatic with the same ROM without any thigh muscle hypotrophy, although
      isokinetic muscle testing did show some weakness of the thigh extensor muscles.
      An x-ray did not show any signs of heterotopic ossification.

PMID- 22369008
TI  - A misinterpretation of the left ventricular non-compaction-adult patient with
      primary pulmonary hypertension.
AB  - Non-compaction of the left ventricle is a rare cardiac malformation, defined as a
      primary cardiomyopathy caused by genetic malformations. Although the pathogenesis
      of this cardiomyopathy is unknown, there are two possible hypotheses (congenital
      and acquired) which lead to arrest in intrauterine endomyocardial morphogenesis.
      We are presenting a case of a 60-year-old woman, with a history of
      bradyarrhythmia, syncope and cyanosis. Two-dimensional echocardiography showed
      the thickened myocardium with prominent trabeculations and deep intertrabecular
      recesses in the two thirds of the apical part of left ventricle walls. The right
      side cavity was enlarged with hypertrophied wall. Tricuspid regurgitation was
      moderate. Systolic pressure in the right ventricle was 70mmHg. Catheterization of
      the right heart showed high pressure in the pulmonary artery. According to
      publications, this is a very rare case with the presence of possible primary
      pulmonary hypertension and non-compaction of the left ventricle.

PMID- 22369009
TI  - [Risk factors for stroke].
AB  - INTRODUCTION: Stroke is the third cause of mortality both in men and in women
      throughout the world. In Serbia, stroke is the first cause of mortality in women
      older than 55 years of age and the second cause of death in men of the same age.
      Both ischemic heart diseases and ischemic stroke correlate with the same
      predisposing, potentially modifiable risk factors (hypertension, abnormal blood
      lipids and lipoproteins, cigarette smoking, physical inactivity, obesity,
      diabetes mellitus). Stroke does not usually occur on its own. Patients with
      stroke have a high prevalence of associated medical problems. These conditions
      may predict the stroke ("preexisting conditions"), occur for the first time after
      stroke ("post-stroke complications"), or present as manifestations of preexisting
      medical conditions after stroke. RISK FACTORS: Risk factors for stroke are
      divided into the three groups: risk factors which cannot be influenced on such
      as: age, gender, positive family history of stroke, race: those which are
      modifiable such as: hypertension, diabetes mellitus, smoking cigarettes, obesity,
      physical inactivity and the third group consists of potential risk factors for
      stroke (consumption of alcohol, hormones, changes in fibrinolysis, changes in
      blood. CONCLUSION: Stroke remains a leading cause of long-term disability and
      premature death of both men and women. Consequently, stroke survivors are often
      handicapped and doomed to sedentary lifestyle which restrains performance of
      activities of daily living, increases the risk for falls, and may contribute to a
      higher risk for recurrent stroke and cardiovascular disease. Prevention of stroke
      is still a great medical and social problem. Further studies are required to
      investigate potential risk factors for the occurrence of stroke as well as the
      measures of primary and secondary prevention.

PMID- 22369010
TI  - [Dr James Lovelock and story about GAIA hypothesis].
AB  - INTRODUCTION: Gaia is the Anglo-Saxon term for the Hellenic term Gea or Ge, which
      means Earth. The GAIA hypothesis was launched almost 40 years ago by the famous
      chemist James Lovelock, who was engaged by the National Aeronautics and Space
      Administration (NASA) to create a sensitive instrument for searching forms of
      extraterrestrial life on other planets. Then he published the book The ages of
      GAIA, which perturbed the world's scientific public of those days. Lovelock
      struck upon this idea in the late sixties of the past century, during the space
      race with Russians, when he was hired hy the National Aeronautics and Space
      Administration to conduct a series of experiments to find and explore life forms
      on the planet Mars. GAIA HYPOTHESIS: Experiments executed by the American module
      Viking failed to trace any life form, as Lovelock had predicted. He called it a
      dead equilibrium. Then he turned to Earth, whose perspective is totally different
      from its first neighbors. Venus and Mars, and is far from a dead equilibrium.
      DAISYWORLD: In this hypothesis. Lovelock represents Earth as one living, giant
      super organism, composed of all living creatures and its material environnent. In
      that super organisnm, the level of oxygen, weather conditions, ocean salinity and
      so on are under constant influence of physical, chemical and biological
      processes, which provide the existence for such life forms on Earth. CONCLUSION:
      Dr James Lovelock represents a pioneer of climatology, and his hypothesis gives a
      unique insight into the correlation of dynamic processes on our planet, no matter
      whether they are of physical or biological nature.

PMID- 22369011
TI  - [Markers of antimicrobial drug resistance in the most common bacteria of normal
      facultative anaerobic intestinal flora].
AB  - INTRODUCTION: Bacteria of normal intestinal flora are frequent carriers of
      markers of antimicrobial drug resistance. Resistance genes may be exchanged with
      other bacteria of normal flora as well as with pathogenic bacteria. The increase
      in the number of markers of resistance is one of the major global health
      problems, which induces the emergence of multi-resistant strains. The aim of this
      study is to confirm the presence of markers of resistance in bacteria of normal
      facultative anaerobic intestinal flora in our region. MATERIAL AND METHODS: The
      experiment included a hundred fecal specimens obtained from a hundred healthy
      donors. A hundred bacterial strains were isolated (the most numerous
      representatives of the normal facultative-anaerobic intestinal flora) by standard
      bacteriological methods. The bacteria were cultivated on Endo agar and SS agar
      for 24 hours at 37 degrees C. Having been incubated, the selected characteristic
      colonies were submitted to the biochemical analysis. The susceptibility to
      antimicrobial drugs was tested by standard disc diffusion method, and the results
      were interpreted according to the Standard of Clinical and Laboratory Standards
      Institute 2010. RESULTS: The marker of resistance were found in 42% of the
      isolated bacteria. The resistance was the most common to ampicillin (42% of
      isolates), amoxicillin with clavulanic acid (14% of isolates), cephalexin (14%)
      and cotrimoxazole (8%). The finding of 12 multiresistant strains (12% of
      isolates) and resistance to ciprofloxacin were significant. The frequency of
      resistance markers was statistically higher in Klebsiella pneumoniae compared to
      Escherichia coli of normal flora. DISCUSSION AND CONCLUSION: The finding of a
      large number of markers of antimicrobial drug resistance among bacteria of normal
      intestinal flora shows that it is necessary to begin with systematic monitoring
      of their antimicrobial resistance because it is an indicator of resistance in the
      population.

PMID- 22369012
TI  - [Hippocratic Oath: professional or ethic code?].
AB  - In order to study the historical relationship of early medical professional codex
      and contemporary demands and challenges, which are currently being placed before
      physicians, the first such text, known as Hippocratic Oath has been re
      translated. According to the source, it is clear that this is a Code of
      professional conduct, primarily for the welfare of patients, and in order to
      maintain and preserve medical authority. All parts of the Oath have been
      discussed and presented, as well as the historical data from which one can see
      how the system in ancient Greece and Rome worked. The study includes historical
      data from that time on two controversial issues: the liability of medical awards,
      and addressing medical services. These are mistakenly considered to belong to the
      text of the Oath. Examples of the amount of medical awards are stated, as well as
      the examples of selflessness and dedication of the physicians in that time. A
      physician was obliged to help by law, only in the case of accidents and injuries.
      It is obvious that "medical doctrine" existed also in this time. Requirements set
      to a doctor were realistic, modest and appropriate to the call, with the main
      purpose of protecting the reputation and dignity of the profession. Despite the
      historical distance, classical text of the Oath is still up to date. In this
      context, ambiguities and errors result from not being familiar with the both, the
      basic text, and the circumstances prevailing at the time and society, in which
      the Oath was made.

PMID- 22369013
TI  - [Baron Gijom Dipitren, Guillaume Dupuytren (1777-1835)].
AB  - Baron Dupuytren, Guillaume (1777-1835), French anatomist, pathologyst and
      surgeon, although was a personal doctor of Napoleon, Lui XVI and Sharles X,
      remain known for Dupuytrene contracture, due to his name, after he described this
      disease of palmar fascia in 1833. He started his education at Paris at age of 12,
      at 18 he was chief demostrator of anatomist prosectors. In 1802. he become
      surgeon assistant and in 1812 professor of surgery. At age of 38 he become
      surgeon-in-chief in Hotel-Dieu the most famous hospital in Europe of that time.
      Dipitren was a dostor of Lui VIII, who gave him the title of baron in 1823. Also,
      he was the doctor of Sharles X, and from Napoleon he was decorated by Legue of
      the Honour. He was the richest doctor of the France, and that time was named
      Dupuytrens time. He was working the whole day, and was dealing with all parts of
      surgery, but he become most prominent in orthopaedics, making connections between
      anatomy, pathology and surgery, what make him popular and famous. Dupuytren dies
      in age of 58 due to the pleural empyema, but he refused surgery. Before that he
      had brain stroke, from which he never recover, although he continue with
      lectures.

PMID- 22369014
TI  - Alexander Brunschwig--110 years from birth September 11, 1901 - August 7, 1969.
AB  - Alexander Brunschwig was very important person in surgical oncology during the
      20th century. He helped Maximow and Bloom to write their well-known histology
      text "A text-book of histology", he was the first to do a one-stage radical
      pancreatoduodenectomy and pelvic exenteration. Doctor Alexander Brunschwig was
      born in El Paso, Texas, on September 11, 1901. He graduated from Rush Medical
      College in 1927. He was named for the chief of gynecology and clinical assistant
      at Clinics and Medical School of the Chicago University in 1933. He became
      professor of surgery at the same University in 1940 where he worked until 1947.
      Doctor Brunschwig moved to New York in 1947 and became the Chief of gynecology in
      Memorial Hospital for Cancer and Allied Diseases and professor of clinical
      surgery at Cornell University at Medical College. He published some very
      important books about oncology, "The Surgery of Pancreatic Tumors", "Radical
      Surgery in Advanced Abdominal Cancer" and "L' Exenteration pelvienne".

PMID- 22369015
TI  - Current options in local anesthesia for groin hernia repairs.
AB  - Inguinal hernia repair is one of the most common procedures in general surgery.
      All anesthetic methods can be used in inguinal hernia repairs. Local anesthesia
      for groin hernia repair had been introduced at the very beginning of the last
      century, and gained popularity following the success reports from the Shouldice
      Hospital, and the Lichtenstein Hernia Institute. Today, local anesthesia is
      routinely used in specialized hernia clinics, whereas its use is still not a
      common practice in general hospitals, in spite of its proven advantages and
      recommendations by current hernia repair guidelines. In this review, the
      technical options for local anaesthesia in groin hernia repairs, commonly used
      local anaesthetics and their doses, potential complications related to the
      technique are evaluated. A comparison of local, general and regional anesthesia
      methods is also presented. Local anaesthesia technique has a short learning curve
      requiring simple training. It is easy to learn and apply, and its use is in open
      anterior repairs a nice way for health care economics. Local anesthesia has been
      shown to have certain advantages over general and regional anesthesia in inguinal
      hernia repairs. It is more economic and requires a shorter time in the operating
      room and shorter stay in the institution. It causes less postoperative pain,
      requires less analgesic consumption; avoids nausea, vomiting, and urinary
      retention. Patients can mobilize and take oral liquids and solid foods much
      earlier. Most importantly, local anesthesia is the most suitable type of
      anesthesia in elder, fragile patients and patients with ASA II-IV scores.

PMID- 22369016
TI  - [Hepatic echinococcal cyst--personal experience and report of a new
      classification system according to WHO].

PMID- 22369017
TI  - [CFTR F508DEL mutation and 5T allele in patients with chronic pancreatitis and
      pancreatic adenocarcinoma].
AB  - INTRODUCTION: Mutations in the CFTR gene may be associated with various types of
      pancreatic pathology and result in higher risk of pancreatic disorders. While
      delta F508 is the most common mutation in cystic fibrosis patients, the allel 5T
      is associated with atypical forms of cystic fibrosis. STUDY AIM: The aim of this
      study was to establish the frequencies of F508del mutation and 5T allele in the
      CFTR gene in patients with chronic pancreatitis and pancreatic cancer, as well as
      to investigate whether these genetic variants represent risk factors for
      pancreatic diseases. STUDY METHODS: The study has encompassed 50 patients with
      chronic pancreatitis and 50 patients with pancreatic adenocarcinoma, as well as
      124 healthy individuals. The analysis of F508del mutation and alleles 5T, 7T and
      9T of the polythymidine tract was performed on DNA extracted from periferal blood
      by PCR-mediated site-direted mutagenesis (PSM) method. RESULTS: The frequency of
      F508del mutation in the group of patients with chronic pancreatitis (3.0%) was
      significantly increased (p = 0.032) in comparison to the group of healthy
      individuals (0.4%), while other analyzed differences were not statistically
      significant. CONCLUSION: The results of this study indicate that F508del mutation
      in the CFTR gene respresents a risk factor for the development of chronic
      pancreatitis.

PMID- 22369018
TI  - [Comparative results of operative and endovascular treatment of intracranial
      aneurysms].
AB  - Therapeutic protoclol for intracranial aneurysm treatment is very complex. In
      depand od patient status and anviografic founding we determinate modality and
      time of treatment. Analysis included 137 patients who were treated in
      Neurosurgical clinic CCS because sponatenus subarachnoid haemorrhage rigine from
      aneurysm belading. We performed direct surgery (microsurgery) in 109 patients. In
      early termine we operated 28 patients (25.69%), in first 24 hours 5 of them. In
      interemdiate period we performed surgery in 9, and other 72 patient we operated
      in postpone period. Embolisation was performed in 22 patinet. GOS form embolised
      patient was 4.636 +/- 0.581 and in operated 4.113 +/- 1.106 (p < 0.05).
      Cumulative experient of Neurisurgical Clinic CCS and summation of international
      experience impose as the best treatment is the treatment which is best known for
      the physician.

PMID- 22369019
TI  - [Surgical treatment of nasal septal deviation (septoplasty) in children].
AB  - The aim of this study was to indicate the importance of surgical treatment of
      nasal septal deviation in children as early correction of functional and cosmetic
      nose deformities. In this study, we presented 76 children, from age of 7 to 15,
      who were surgical treated for the reason of nasal septal deviation starting from
      January 2001. to December 2009. There were 48 (63%) male and 28 (37%) female
      patients. The lowest number of patients were between 7 and 9 years old--5 (6.5%),
      between 10 and 12 years--28 (37%) and 43--(56.5%) between 13 and 15 years. Only 7
      (9%) patients indicated genetics inheritance, and 11 of them (14%) could not
      determine the exact cause of deviation origin. References taken from the parents
      showed that nasal septal deviation developed like consequence of injury in 58
      (76%) cases. We used closed technique of septoplasty with hemitransfictional
      incision and sub mucosal resection. Deviated portion of septum was completely
      removed. Patients felt improvement in nose breathing in 65 (85%) cases. The most
      often complication was nasal obstruction in 6 (8%) cases which occurred due to
      the insufficient removal of deviated portion. We also had a septal perforation in
      one and abscess of nasal septum in another case. There were no esthetic
      deformities.Surgical treatment of nasal septal deviation in children must to be
      conservative and limited on injured part of septum. After the operation nose
      breathing significantly improved, without consequences on esthetic appearance or
      the growth of central part of a face.

PMID- 22369020
TI  - Bloodless esophageal replacement in children with corrosive esophageal strictures
      -report of two cases.
AB  - BACKGROUND: Esophageal replacement is major procedure with high risk for
      perioperative allogeneic blood transfusion (ABT), especially in pediatric
      patients due to nutritive deficiency, anemia, small body weight and blood volume.
      Autologous blood policy is particularly important in female children. METHODS: We
      present treatment strategy with the aim of avoiding ABT, that have been applied
      in two female pediatric patients with caustic stricture of thoracic esophagus.
      The patients were 7 and 8 years old, with body weight 34 and 23.5 kg,
      respectively. Protocol was based on the stimulation of haematopoetic system with
      erythropoietin, iron therapy and preoperative autologous blood donation (PABD).
      In the first patient, with a history of previous retrosternal bypass
      esophagocoloplasty and extraction of necrotic colonic graft, delayed
      reconstruction--transhiatal subtotal esophagectomy and gastric pull-up with
      cervical anastomosis were performed. In the second patient, repeated ineffective
      dilatations of esophageal stricture were reason for retrosternal left colon
      interposiotion and exclusion of native esophagus. RESULTS: No adverse events were
      attributed to preoperative blood donation period. No allogenic blood products
      were used during perioperative period. Both patients had uneventful postoperative
      course. CONCLUSION: In specialized institutions for esophageal surgery, PABD with
      administration of erythropoietin and iron therapy, enable bloodless esophageal
      replacement, even in children.

PMID- 22369021
TI  - Radical cystectomy and orthotopic ileal bladder substitution with serous lined
      extramural ureteral reimplantation--report of 8 cases.
AB  - OBJECTIVES: We review the functional and oncoloic outcomes of radical cystectomy
      and orthotog pic ileal bladder substitution with serous lined extramural ureteral
      reimplantation. MATERIAL AND METHODS: From 1985 to 2009 a total of 125 male
      patients (mean age 62.5 years, range 37 to 74) underwent orhotopic ileal bladder
      substitute at the urological Clinic in Belgrade. Of these, 8 patients underwent
      modified technique with serous lined extramural ureteral reimplantation. The
      median follow-up (available for 88 patients) period was 30 (2-72) months.
      RESULTS: Perioperative lethality was nil. Modified operative technique was
      associated with low postoperative complication rates and without ureteric
      implantation site stenosis, reflux or deteriorization of renal function. All
      patients had satisfied day and night continence rates. CONCLUSION: The serous
      lined extramural ureteral reimplantation is an attractive technique regarding its
      safety, versality and functional outcome. It is especially favorable for
      reimplantation to ureters of various calibers as well as dilated ureters.

PMID- 22369022
TI  - Is routine cystoscopy justified in female stress urinary incontinence?
AB  - The investigation of women with SUI the Serbian urologist traditionally begins
      with cystoscopy to reduced risk of bladder tumor. There is no doubt regarding its
      ability to detect bladder cancer presented with characteristic symptoms or
      pathologic results of urinalyses. We discuss its routine use in patients
      presenting with symptomatology of SUI. The retrospective study was performed in
      order to evaluate clinical justifiability and cost/benefit ratio of routine
      cystoscopy in women with stress urinary incontinence (SUI) whose were surgically
      treated. We reviewed records of 95 female, mean age 56,5 years (rang 46-78) who
      underwent SUI surgery at eight-year period. The clinical variables, including
      urinary symptoms, results of urinalyses, ultrasound records and cystoscopic
      findings, were obtained from the hospital reports. Insignificantly abnormal
      cystoscopic findings were reported in 31% patients (vagina-like epithel,
      trigonitis, uterus wall impression, hyperemia, polypoid proliferation and mild
      trabeculation). No cases of malignancy were incidentally discovered. In female
      SUI cystoscopic finding was insignificantly abnormal and was not influenced
      further therapy and contraindicated the planned SUI surgery. Routine cystoscopy
      in women with SUI cannot be justified only by customary practice or tradition of
      older generation urologists.

PMID- 22369023
TI  - Quality of life and functional capacity one year after coronary artery bypass
      graft surgery.
AB  - OBJECTIVES: To analyze functional capacity and quality of life of patients one
      year after coronary artery bypass graft surgery (CABG) and identify factors that
      influence them in order to accomplish maximal recovery. METHODS: Observational
      study included 89 patients undergoing elective CABG, who were tested
      preoperatively and one year after operation using Short form 12 item health
      survey (SF-12), Duke Activity Status Index (DASI) questionnaire and questionnaire
      regarding participation in rehabilitation program. RESULTS: After one year, DASI
      and quality of life-physical component summary score (SF-12 PCS) significantly
      improved (p < 0.001; p < 0.05). No statistically significant improvement in
      mental component summary has been registered. In domains of physical component
      summary, only general health was significantly better (p < 0.05). There was
      moderate correlation of SF-12 PCS postoperatively with SF-12 mental component
      summary (SF-12 MCS) preoperatively. DASI scores preoperatively and
      postoperatively are found to be significantly higher in men comparing to women (p
      < 0.05). Multiple regression analysis found DASI preoperatively (R2 = 0.62, beta
      = 0.42, p < 0.05) and age (beta = -0.53, p < 0.05) to be significant predictors
      of DASI postoperatively in women. Enrollment in rehabilitation program didn't
      influence DASI and SF-12 scores one year after CABG. CONCLUSIONS: Although
      functional capacity and physical component of quality of life improved, factors
      that influence them still remain unclear. It seems that mental health status and
      personality profile, as well as the alternative modalities of rehabilitation,
      might play important role in long lasting effects of improvement.

PMID- 22369024
TI  - Kinesiological characteristics of ankle joint and rearfoot motion.
AB  - Kinesiological analysis of tarsal bones provides better understanding of foot
      disorders, especially in early childhood, when radiography is hindered by delayed
      ossification of foot bones. Children begin to walk in the age of 9-15 months,
      with rearfoot inversion only in initial contact phase, while inversion during
      terminal stance phase is delayed. Adult walking pattern is usually established at
      six years of age. Talocrural joint axis medial slope shifts during movements
      depending on the what part of talus comes in contact with maleolli. As a result,
      plantar flexion includes valgus, and dorsal flexion includes varus inclination.
      Subtalar joint axis highly varies among individuals: from 200-680 in sagittal and
      from 40-470 in frontal plane, with impact on coupled lower leg rotation movements
      around longitudinal axis. Midtarsal joint has two axes, and their position
      control the rigidity of forefoot and midfoot kinetic chain. Movement planes of
      tarsal bones strongly influence walking pattern as well as secure foot
      development.

PMID- 22369025
TI  - Foot examination in the period of development.
AB  - Feet are maybe the key part of our musculoskeletal system that establishes
      upright position and movement. Their role is multiple--they maintain the balance
      of the body, push the body forward when walking and absorb mechanical pressure
      created in contact with the surface. Therefore, correct anatomic and functional
      development of foot is of vital importance. The most frequent reasons for
      examination of foot in the period of development are pain, deformity and
      incorrect walk. Our task is to detect the cause of the problem with clinical
      examination in the shortest possible period of time or to assess which additional
      diagnostic procedure would be the most suitable. A clinical examination of foot
      in the period of development involves inspection, palpation, percussion,
      auscultation, examination of joint mobility, examination of sensory-motor
      function and conducting specific tests. In some cases detailed and properly
      conducted clinical examination can prove to be sufficient to establish a complete
      and accurate diagnosis. Patients of this specific age may be insufficiently
      cooperative, mistrustful, shy or even afraid. Our approach and manipulations
      during the clinical examination need to be adapted completely to such patients
      and their characteristics.

PMID- 22369026
TI  - Clubfoot in children.
AB  - Clubfoot, or talipes equinovarus, is a deformity consisting of equinus, varus,
      and adductus foot deformity. The true etiology of congenital clubfoot is unknown;
      several theories have been proposed. The pathology of the individual bones
      contributes to the clubfoot deformity and soft tissue contractures around the
      ankle and talocalcaneonavicular joint maintains the deformity and involve
      muscles, tendons, tendon sheaths, ligaments and joint capsules. Various treatment
      regimens have been proposed, including the use of corrective splinting, taping,
      and casting. Surgery in clubfoot is indicated for deformities that do not respond
      to conservative treatment by serial manipulation and casting. Surgery in the
      treatment of clubfoot must be tailored to the age of the child and to the
      deformity to be corrected. The main goals of treatment is the painless,
      functional and anatomical normal foot without need for custom made footwear, and
      those can be achieved after detailed, indivudial approach with great experience
      in pediatric orthopedics.

PMID- 22369027
TI  - Flatfoot in children.
AB  - Foot arches are defined by the position of bones and stabilized by active and
      passive soft tissue structures. The most significant foot arches are
      longitudinal, medial and lateral. During lifetime they develop and change, while
      the most significant disorder represents the flatfoot. During the first two years
      of life, the flatfoot in full weight bearing position is considered a normal
      physiological condition, while in later age it represents a deformity requiring
      additional diagnostics and treatment. The flexible flatfoot is caused by
      ligamentous laxity, it is mostly pain-free and is treated symptomatically
      (prescription of adequate shoes and kinesitherapy). The rigid foot is most often
      caused by bone changes (tarsal coalition, vertical congenital talus) occurring
      idiopathically or within neuromuscular pathological conditions, with mostly
      present pain problems. In such cases treatment is also initiated by non-surgical
      methods, however, some type of surgical treatment is most frequently necessary to
      be used.

PMID- 22369028
TI  - Hallux valgus.
AB  - Hallux valgus is a complex deformity of the forefoot. Beside the lateral
      deviation of the first metatarsophalangeal joint angle exceeding 15-20 degrees
      and intermetatarsalvarus exceeding 8-9 degrees, it is also characterized by
      extensive changes of the soft tissue arch, sesamoid mechanism and
      metatarsocuneiform joint. It occurs almost exclusively in humans wearing shoes.
      Although in some measure it can be treated non-operatively, by corrective
      separators and inserts, operative treatment is predominant. There are numerous
      operative procedures aimed at the correction of the deformity and inducing normal
      biomechanics of the forefoot. There are seven conceptually different procedures
      starting from simple bunionectomy, through various soft tissue procedures,
      metatarsal and phalangeal osteotomies, to resection arthroplasty and
      metatarsophalangeal arthrodesis. All have clear indications, and none of them has
      advantages over the others. In accordance with the etiopathogenesis of the
      disease prevention is easy; wearing comfortable shoes.

PMID- 22369029
TI  - Physical treatment of foot deformities in childhood.
AB  - During the period of development foot deformities can occur, not only during the
      growth and development, but also in the later age. The most frequent foot
      deformity is flatfoot, congenital club foot and hallux valgus. Prior to the
      decision on surgical treatment of the deformity, whenever possible the patient
      should be referred for physical therapy that may yield acceptable results in
      specific treatment phases. The basis of the treatment involves kinesitherapy,
      application of certain agents (thermotherapy, electrotherapy, ultrasound) and
      orthosis for maintaining corrections. If such therapy does not yield satisfactory
      results, the deformity is surgically corrected. After surgical correction,
      physical procedures can contribute to more rapid recovery and decrease possible
      complications (pain, edema, complex regional pain syndrome--Mb Sudec), which can
      follow the surgical correction of the deformity. In addition, the obligatory form
      of rehabilitation also involves kinesitherapy.

PMID- 22369030
TI  - [Psoas major abscess by heroin addictive patients--a case report].
AB  - Drug abuse is related to many medical complications, which depend on the drug
      type, dose injected, the method of delivery and site of injection. We report a
      case of psoas abscess in young heroin addict, HIV negative, who was admitted in
      Emergency Center of Clinical Center in Belgrade because of fever, anaemia,
      prostration and right groin pain. Clinical and radiological examination were
      performed. CT showed large abscess of the right psoas muscle, 12 x 4 cm large.
      Treatment included percutaneous drainage and administration of iv antibiotics.
      There is regression of inflamation. At discharge patient was in good condition
      without signs of infection.

PMID- 22369031
TI  - [Meckel's diverticulum--acute abdomen in 8th decade of life].
AB  - Meckel's diverticulum represents one of the most common congenital anomalies of
      the gastrointestinal system. It appears in 1-3% of the general population. In
      this case study we presented 72-year-old male patient who was admitted in the
      Center for Abdominal Surgery, Clinical Center of Montenegro. The symptoms were
      diffuse, severe abdominal pain, nausea and vomiting with intestinal obstruction.
      After the preoperative diagnostic procedures we performed resection of the
      terminal ileum and T-T anastomosis. Whenever the patient has the clinical
      findings of acute abdomen and no matter if patient is in elderly, we should think
      on complications of the Meckel's diverticulum.

PMID- 22369032
TI  - Selection of birefringent spermatozoa under Polscope: effect on intracytoplasmic
      sperm injection outcome.
AB  - The ideal method for sperm selection during Intracytoplasmic sperm injection
      (ICSI) is still ill-defined. Identification of a viable spermatozoon amongst
      immotile spermatozoa for ICSI often becomes difficult. Ninety-six ICSI cycles
      were selected and divided into Group A (azoospermic, n = 58) and Group B
      (complete asthenozoospermic, n = 38). Oocytes having birefringent meiotic spindle
      and zona pellucida thickness <20 MUm were selected for ICSI. Groups A and B were
      further divided into A1, A2 and B1, B2, respectively, based on the type of ICSI
      performed. In Group A1, a motile spermatozoon with normal morphology was injected
      into a metaphase-II (M-II) oocyte. In Group B1, spermatozoon showing coiling of
      tail following modified hypo-osmotic swelling test was injected into M-II
      oocytes. In Groups A2 and B2, ICSI was performed by injecting a spermatozoan with
      birefringent head. Pronuclear morphology, fertilisation rate, embryo grading and
      pregnancy rate were assessed. ICSI outcome measures were better in Group A2 than
      in Group A1 but were statistically insignificant. However, significantly higher
      percentage of Z1 and Z2 zygotes, Grade I and Grade II embryos and pregnancy rate
      were observed in Group B2 as compared to Group B1. Selection of birefringent
      spermatozoa shows promising results in asthenozoospermic men and men undergoing
      testicular sperm aspiration or extraction before ICSI.

PMID- 22369033
TI  - Current and future techniques in the evaluation of dysphagia.
AB  - Dysphagia is common in the general population, and is generally due to either
      mechanical obstruction or dysmotility. Patient demographics and symptom
      evaluation are often useful in determining the likely cause, and guide subsequent
      investigation and management. Oropharyngeal dysphagia is usually caused by
      neurological conditions where treatment options are limited. Conversely, many of
      the esophageal causes of dysphagia are amenable to therapy. Gastroscopy is often
      the first test of choice, given its diagnostic and therapeutic potential,
      especially when mechanical causes are concerned. Esophageal motor function can be
      assessed by a variety of techniques, ranging from radiology such as barium
      swallow, to dedicated motility tests such as manometry and impedance monitoring.
      The choice of test relies on the clinical indication and the results should be
      interpreted in conjunction with the patients' symptoms. High-resolution manometry
      with topography is now the new benchmark for motility studies. Several new
      techniques for motility testing have also become available, such as esophageal
      ultrasound and functional lumen imaging probe, but are currently limited to the
      research setting.

PMID- 22369034
TI  - Reduction of errors during practice facilitates fundamental movement skill
      learning in children with intellectual disabilities.
AB  - BACKGROUND: Children with intellectual disabilities (ID) have been found to have
      inferior motor proficiencies in fundamental movement skills (FMS). This study
      examined the effects of training the FMS of overhand throwing by manipulating the
      amount of practice errors. METHODS: Participants included 39 children with ID
      aged 4-11 years who were allocated into either an error-reduced (ER) training
      programme or a more typical programme in which errors were frequent (error
      strewn, ES). Throwing movement form, throwing accuracy, and throwing frequency
      during free play were evaluated. RESULTS: The ER programme improved movement
      form, and increased throwing activity during free play to a greater extent than
      the ES programme. Furthermore, ER learners were found to be capable of engaging
      in a secondary cognitive task while manifesting robust throwing accuracy
      performance. CONCLUSIONS: The findings support the use of movement skills
      training programmes that constrain practice errors in children with ID,
      suggesting that such approach results in improved performance and heightened
      movement engagement in free play.

PMID- 22369035
TI  - Maximum predictive power of the microarray-based models for clinical outcomes is
      limited by correlation between endpoint and gene expression profile.
AB  - BACKGROUND: Microarray data have been used for gene signature selection to
      predict clinical outcomes. Many studies have attempted to identify factors that
      affect models' performance with only little success. Fine-tuning of model
      parameters and optimizing each step of the modeling process often results in over
      fitting problems without improving performance. RESULTS: We propose a
      quantitative measurement, termed consistency degree, to detect the correlation
      between disease endpoint and gene expression profile. Different endpoints were
      shown to have different consistency degrees to gene expression profiles. The
      validity of this measurement to estimate the consistency was tested with
      significance at a p-value less than 2.2e-16 for all of the studied endpoints.
      According to the consistency degree score, overall survival milestone outcome of
      multiple myeloma was proposed to extend from 730 days to 1561 days, which is more
      consistent with gene expression profile. CONCLUSION: For various clinical
      endpoints, the maximum predictive powers of different microarray-based models are
      limited by the correlation between endpoint and gene expression profile of
      disease samples as indicated by the consistency degree score. In addition,
      previous defined clinical outcomes can also be reassessed and refined more
      coherent according to related disease gene expression profile. Our findings point
      to an entirely new direction for assessing the microarray-based predictive models
      and provide important information to gene signature based clinical applications.

PMID- 22369036
TI  - Pulmonary epithelial apoptosis in fetal down syndrome: not higher than normal.
AB  - Children with Down syndrome (DS) are at high risk for acute lung injury (ALI).
      Pulmonary epithelial apoptosis is an important factor in the pathophysiology of
      ALI. Whether the risk of ALI in DS is associated with a high level of pulmonary
      epithelial apoptosis is not known. We hypothesized that the percentage of
      apoptotic epithelial cells is higher in DS than in control lungs. Lung tissue
      sections from autopsies of 21 fetuses with DS and 12 controls were stained with
      antibodies against the epithelial marker pan-cytokeratin (CK) and apoptosis
      marker activated caspase-3 (aC3). Spectral imaging software was used to quantify
      the mean percentage of pixels that showed colocalization of CK and aC3. Mean
      (standard deviation [SD]) gestational age in weeks was 18.7 (1.4) in DS and 18.9
      (2.0) in controls (P  =  0.67). The mean (SD) percentage of CK-positive pixels
      was 27.2% (4.7%) in DS compared to 27.1% (6.2%) in controls (P  =  0.97). The
      median (interquartile range [IQR]) percentage of CK-positive pixels that showed
      colocalization of aC3 was 0.16% (0.18%) in DS compared to 0.27% (0.24%) in
      controls (P  =  0.45). The mean (SD) number of CK-positive pixels increased from
      22.5% (5.2%) to 30.4% (4.6%) with the appearance of saccular morphology in
      controls but not in DS (P  =  0.01). The percentage of apoptotic epithelial cells
      in DS fetal lungs does not differ from that in controls. However, we did find a
      difference in the development of epithelial structures between DS and controls
      that may be associated with anomalies in alveolar development found at birth in
      DS.

PMID- 22369038
TI  - Porous polymer membranes via selectively wetted surfaces.
AB  - Here, we show that porous polymeric membranes can be prepared using the
      principles of offset printing: an offset printing plate is structured into
      hydrophobic and hydrophilic regions with the help of photolithography and is
      selectively wetted with a solution of calcium chloride in water at the
      hydrophilic regions. Then, a polymer solution (poly(methyl methacrylate) in
      chloroform) is applied to this surface and forms a hydrophobic layer that is
      structured by the aqueous droplets. Deviating from standard offset printing, this
      layer is not transferred to another surface in its liquid state but is solidified
      and subsequently is separated from the printing plate. The thickness of the
      polymer film is chosen in such a way that the aqueous droplets on the surface
      protrude from the film. Thus, we obtain polymer membranes with pores in the size
      of the protruding aqueous droplets. These membranes are then characterized by the
      filtration of model dispersions.

PMID- 22369037
TI  - Quantification and clustering of phenotypic screening data using time-series
      analysis for chemotherapy of schistosomiasis.
AB  - BACKGROUND: Neglected tropical diseases, especially those caused by helminths,
      constitute some of the most common infections of the world's poorest people.
      Development of techniques for automated, high-throughput drug screening against
      these diseases, especially in whole-organism settings, constitutes one of the
      great challenges of modern drug discovery. METHOD: We present a method for
      enabling high-throughput phenotypic drug screening against diseases caused by
      helminths with a focus on schistosomiasis. The proposed method allows for a
      quantitative analysis of the systemic impact of a drug molecule on the pathogen
      as exhibited by the complex continuum of its phenotypic responses. This method
      consists of two key parts: first, biological image analysis is employed to
      automatically monitor and quantify shape-, appearance-, and motion-based
      phenotypes of the parasites. Next, we represent these phenotypes as time-series
      and show how to compare, cluster, and quantitatively reason about them using
      techniques of time-series analysis. RESULTS: We present results on a number of
      algorithmic issues pertinent to the time-series representation of phenotypes.
      These include results on appropriate representation of phenotypic time-series,
      analysis of different time-series similarity measures for comparing phenotypic
      responses over time, and techniques for clustering such responses by similarity.
      Finally, we show how these algorithmic techniques can be used for quantifying the
      complex continuum of phenotypic responses of parasites. An important corollary is
      the ability of our method to recognize and rigorously group parasites based on
      the variability of their phenotypic response to different drugs. CONCLUSIONS: The
      methods and results presented in this paper enable automatic and quantitative
      scoring of high-throughput phenotypic screens focused on helmintic diseases.
      Furthermore, these methods allow us to analyze and stratify parasites based on
      their phenotypic response to drugs. Together, these advancements represent a
      significant breakthrough for the process of drug discovery against
      schistosomiasis in particular and can be extended to other helmintic diseases
      which together afflict a large part of humankind.

PMID- 22369039
TI  - Selective alkylation of (hetero)aromatic amines with alcohols catalyzed by a
      ruthenium pincer complex.
AB  - A readily available pincer ruthenium(II) complex catalyzes the selective
      monoalkylation of (hetero)aromatic amines with a wide range of primary alcohols
      (including pyridine-, furan-, and thiophene-substituted alcohols) with high
      efficiency when used in low catalyst loadings (1 mol %). Tertiary amine formation
      via polyalkylation does not occur, making this ruthenium system an excellent
      catalyst for the synthesis of sec-amines.

PMID- 22369040
TI  - Measuring mental toughness in sport: a psychometric examination of the
      psychological performance inventory-a and its predecessor.
AB  - Touted as a multidimensional measure of mental toughness in sport, this study
      explored the psychometric properties of the Psychological Performance Inventory
      (PPI; Loehr,  1986 ) and its successor the Psychological Performance Inventory-A
      (PPI-A; Golby, Sheard, & Van Wersch,  2007 ). Confirmatory factor analysis was
      employed to examine the extent to which data collected with 333 Australian
      footballers aged between 15 and 18 years (M = 16.88, SD = .71) fitted the a
      priori measurement models of both inventories. The results did not support the
      psychometric properties of the PPI both in terms of model fit and internal
      consistency. Although model fit data for the PPI-A were encouraging, inadequate
      levels of internal consistency were evidenced. Convergent validity analyses
      involving measures of achievement goals and global mental toughness generally
      supported the validity of the PPI and PPI-A subscales. Taken together with
      previous research (e.g., Middleton et al.,  2004 ), caution is urged when
      considering the use of the PPI as a measure of mental toughness in sport.
      Although the empirical data were generally supportive of the psychometric
      properties of the PPI-A, conceptual (e.g., lack of conceptual underpinnings) and
      methodological (i.e., revalidated a flawed inventory) concerns become important
      factors when considering the PPI-A as a measure of mental toughness.

PMID- 22369041
TI  - Key informant perspectives on policy- and service-level challenges and
      opportunities for delivering integrated sexual and reproductive health and HIV
      care in South Africa.
AB  - BACKGROUND: Integration of sexual and reproductive health (SRH) and HIV services
      is a policy priority, both globally and in South Africa. Recent studies examining
      SRH/HIV integration in South Africa have focused primarily on the SRH needs of
      HIV patients, and less on the policy and service-delivery environment in which
      these programs operate. To fill this gap we undertook a qualitative study to
      elicit the views of key informants on policy-and service-level challenges and
      opportunities for improving integrated SRH and HIV care in South Africa. This
      study comprised formative research for the development of an integrated service
      delivery model in KwaZulu-Natal (KZN) Province. METHODS: Semi-structured in-depth
      interviews were conducted with 21 expert key informants from the South African
      Department of Health, and local and international NGOs and universities. Thematic
      codes were generated from a subset of the transcripts, and these were modified,
      refined and organized during coding and analysis. RESULTS: While there was
      consensus among key informants on the need for more integrated systems of SRH and
      HIV care in South Africa, a range of inter-related systems factors at policy and
      service-delivery levels were identified as challenges to delivering integrated
      care. At the policy level these included vertical programming, lack of policy
      guidance on integrated care, under-funding of SRH, program territorialism, and
      weak referral systems; at the service level, factors included high client load,
      staff shortages and insufficient training and skills in SRH, resistance to
      change, and inadequate monitoring systems related to integration. Informants had
      varying views on the best way to achieve integration: while some favored a one
      stop shop approach, others preferred retaining sub-specialisms while
      strengthening referral systems. The introduction of task-shifting policies and
      decentralization of HIV treatment to primary care provide opportunities for
      integrating services. CONCLUSION: Now that HIV treatment programs have been
      scaled up, actions are needed at both policy and service-delivery levels to
      develop an integrated approach to the provision of SRH and HIV services in South
      Africa. Concurrent national policies to deliver HIV treatment within a primary
      care context can be used to promote more integrated approaches.

PMID- 22369042
TI  - Activated paper surfaces for the rapid hybridization of DNA through capillary
      transport.
AB  - The development of low-cost, accurate, and equipment-free diagnostic tests is
      crucial to many clinical, laboratory, and field applications, including forensics
      and medical diagnostics. Cellulose fiber-based paper is an inexpensive,
      biodegradable, and renewable resource, the use of which as a biomolecule
      detection matrix and support confers several advantages compared to traditional
      materials such as glass. In this context, a new, facile method for the
      preparation of surface functionalized papers bearing single-stranded probe DNA
      (ssDNA) for rapid target hybridization via capillary transport is presented.
      Optimized reaction conditions were developed that allowed the direct, one-step
      activation of standard laboratory filters by the inexpensive and readily
      available bifunctional linking reagent, 1,4-phenylenediisothiocyanate. Such
      papers were thus amenable to subsequent coupling of amine-labeled ssDNA under
      standard conditions widely used for glass-based supports. The intrinsic wicking
      ability of the paper matrix facilitated rapid sample elution through arrays of
      probe DNA, leading to significant, detectable hybridization in the time required
      for the sample liquid to transit the vertical length of the strip (less than 2
      min). The broad applicability of these paper test strips as rapid and specific
      diagnostics in "real-life" situations was exemplified by the discrimination of
      amplicons generated from canine and human mitochondrial and genomic DNA in mock
      forensic samples.

PMID- 22369043
TI  - PRODIS: a proteomics data management system with support to experiment tracking.
AB  - BACKGROUND: A research area that has greatly benefited from the development of
      new and improved analysis technologies is Proteomics and large amounts of data
      have been generated by proteomic analysis as a consequence. Previously, the
      storage, management and analysis of these data have been done manually. This is,
      however, incompatible with the volume of data generated by modern proteomic
      analysis. Several attempts have been made to automate the tasks of data analysis
      and management. In this work we propose PRODIS (Proteomics Database Integrated
      System), a system for proteomic experimental data management. The proposed system
      enables an efficient management of the proteomic experimentation workflow,
      simplifies controlling experiments and associated data and establishes links
      between similar experiments through the experiment tracking function. RESULTS:
      PRODIS is fully web based which simplifies data upload and gives the system the
      flexibility necessary for use in complex projects. Data from Liquid
      Chromatography, 2D-PAGE and Mass Spectrometry experiments can be stored in the
      system. Moreover, it is simple to use, researchers can insert experimental data
      directly as experiments are performed, without the need to configure the system
      or change their experiment routine. PRODIS has a number of important features,
      including a password protected system in which each screen for data upload and
      retrieval is validated; users have different levels of clearance, which allow the
      execution of tasks according to the user clearance level. The system allows the
      upload, parsing of files, storage and display of experiment results and images in
      the main formats used in proteomics laboratories: for chromatographies the
      chromatograms and lists of peaks resulting from separation are stored; For 2D
      PAGE images of gels and the files resulting from the analysis are stored,
      containing information on positions of spots as well as its values of intensity,
      volume, etc; For Mass Spectrometry, PRODIS presents a function for completion of
      the mapping plate that allows the user to correlate the positions in plates to
      the samples separated by 2D-PAGE. Furthermore PRODIS allows the tracking of
      experiments from the first stage until the final step of identification, enabling
      an efficient management of the complete experimental process. CONCLUSIONS: The
      construction of data management systems for Proteomics data importing and storing
      is a relevant subject. PRODIS is a system complementary to other proteomics tools
      that combines a powerful storage engine (the relational database) and a friendly
      access interface, aiming to assist Proteomics research directly at data handling
      and storage.

PMID- 22369044
TI  - RNA interference links oxidative stress to the inhibition of heat stress
      adaptation.
AB  - Increased oxidative stress is associated with various diseases and aging, while
      adaptation to heat stress is an important determinant of survival and contributes
      to longevity. However, the impact of oxidative stress on heat resistance remains
      largely unclear. AIM: In this study we investigated how oxidative stress impinges
      on heat stress responses. RESULTS: We report that hydrogen-peroxide (H(2)O(2))
      pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70
      expression in mammalian cells, as well as acquired thermotolerance in the
      nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate
      that elimination of RNA interference by silencing key enzymes in microRNA
      biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of
      aged and H(2)O(2)-elimination compromised (catalase-2 and peroxiredoxin-2
      deficient) worms. INNOVATION AND CONCLUSION: These results uncover a novel post
      transcriptional element in the regulation of heat stress adaptation under
      oxidative conditions that may have implications in disease susceptibility and
      aging.

PMID- 22369045
TI  - Steric and allosteric factors prevent simultaneous binding of transferrin-binding
      proteins A and B to transferrin.
AB  - The ability to acquire iron directly from host Tf (transferrin) is an adaptation
      common to important bacterial pathogens belonging to the Pasteurellaceae,
      Moraxellaceae and Neisseriaceae families. A surface receptor comprising an
      integral outer membrane protein, TbpA (Tf-binding protein A), and a surface
      exposed lipoprotein, TbpB (Tf-binding protein B), mediates the iron acquisition
      process. TbpB is thought to extend from the cell surface for capture of Tf to
      initiate the process and deliver Tf to TbpA. TbpA functions as a gated channel
      for the passage of iron into the periplasm. In the present study we have mapped
      the effect of TbpA from Actinobacillus pleuropneumoniae on pTf (porcine Tf) using
      H/DX-MS (hydrogen/deuterium exchange coupled to MS) and compare it with a
      previously determined binding site for TbpB. The proposed TbpA footprint is
      adjacent to and potentially overlapping the TbpB-binding site, and induces a
      structural instability in the TbpB site. This suggests that simultaneous binding
      to pTf by both receptors would be hindered. We demonstrate that a recombinant
      TbpB lacking a portion of its anchor peptide is unable to form a stable ternary
      TbpA-pTf-TbpB complex. This truncated TbpB does not bind to a preformed Tf-TbpA
      complex, and TbpA removes pTf from a preformed Tf-TbpB complex. Thus the results
      of the present study support a model whereby TbpB 'hands-off' pTf to TbpA, which
      completes the iron removal and transport process.

PMID- 22369046
TI  - I am what I do, not what I have: the differential centrality of experiential and
      material purchases to the self.
AB  - What kinds of purchases do the most to make us happy? Previous research (Carter &
      Gilovich, 2010; Van Boven & Gilovich, 2003) indicates that experiences, such as
      vacations and concerts, are more likely to do so than material possessions, such
      as clothes and electronic gadgets. The present research was designed to explore 1
      potential explanation for this result, namely, that experiences tend to be more
      closely associated with the self than possessions. The authors first show that
      people tend to think of their experiential purchases as more connected to the
      self than their possessions. Compared with their material purchases, participants
      drew their experiential purchases physically closer to the self (Study 1), were
      more likely to mention them when telling their life story (Study 2), and felt
      that a purchase described in terms of its experiential, rather than its material,
      qualities would overlap more with their sense of who they are (Study 4).
      Participants also felt that knowing a person's experiential purchases, compared
      with their material purchases, would yield greater insight into that person's
      true self (Studies 3A-3C). The authors then show that the tendency to cling more
      closely to cherished experiential memories is connected to the greater
      satisfaction people derive from experiences than possessions (Study 5).

PMID- 22369047
TI  - The origins of deference: when do people prefer lower status?
AB  - Although the desire for high status is considered universal, prior research
      suggests individuals often opt for lower status positions. Why would anyone favor
      a position of apparent disadvantage? In 5 studies, we found that the broad
      construct of status striving can be broken up into two conceptions: one based on
      rank, the other on respect. While individuals might universally desire high
      levels of respect, we find that they vary widely in the extent to which they
      strive for high-status rank, with many individuals opting for middle- or low
      status rank. The status rank that individuals preferred depended on their self
      perceived value to the group: when they believed they provided less value, they
      preferred lower status rank. Mediation and moderation analyses suggest that
      beliefs about others' expectations were the primary driver of these effects.
      Individuals who believed they provided little value to their group inferred that
      others expected them to occupy a lower status position. Individuals in turn
      conformed to these perceived expectations, accepting lower status rank in such
      settings.

PMID- 22369048
TI  - The assessment of GFR after orthotopic liver transplantation using cystatin C and
      creatinine-based equations.
AB  - The measurement of kidney function after orthotopic liver transplantation (OLT)
      is still a clinical challenge. Cystatin C (CysC) has been proposed as a more
      accurate marker of renal function than serum creatinine (sCr). The aim of this
      study was to evaluate sCr- and CysC-based equations including the Chronic kidney
      disease (CKD)-EPI to determine renal function in liver transplant recipients.
      CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular
      filtration rate (GFR) was calculated using the MDRD 4, the Cockroft-Gault, Hoek,
      Larsson, and the CKD-EPI equations based on sCr and/or CysC. As reference method,
      inulin clearance (IC) was estimated. Bias, precision, and accuracy of each
      equation were assessed and compared with respect to IC. Forty-five percent had a
      GFR < 60 ml/min/1.73 m(2) according to the IC. The Larsson, the Hoek and the CKD
      EPI-CysC formula identified the highest percentage of patients with CKD correctly
      (88%, 88%, and 84%, respectively). The sCr-based equations showed less bias than
      CysC-based formulas with a similar precision. All CysC-based equations were
      superior as compared with sCr-based equations in the assessment of renal function
      in patients with an IC < 60 ml/min/1.73 m(2).

PMID- 22369049
TI  - Aerosol-mediated transport and deposition of brominated diphenyl ethers to
      Antarctica.
AB  - Brominated diphenyl ethers (BDE47, 99, 100, and 209) were measured in air, snow
      and sea ice throughout western Antarctica between 2001 and 2007. BDEs in
      Antarctic air were predominantly associated with aerosols and were low compared
      to those in remote regions of the northern hemisphere, except in Marguerite Bay
      following the fire at Rothera research station in Sept 2001, indicating that this
      event was a local source of BDE209 to the Antarctic environment. Aerosol
      BDE47/100 reflects a mixture of commercial pentaBDE products; however, BDE99/100
      is suggestive of photodegradation of BDE99 during long-range atmospheric
      transport (LRAT) in the austral summer. BDEs in snow were lower than predicted
      based on snow scavenging of aerosols indicating that atmospheric deposition
      events may be episodic. BDE47, -99, and -100 significantly declined in Antarctic
      sea ice between 2001 and 2007; however, BDE209 did not decline in Antarctic sea
      ice over the same time period. Significant losses of BDE99 and -100 from sea ice
      were recorded over a 19 day period in spring 2001 demonstrating that seasonal ice
      processes result in the preferential loss of some BDEs. BDE47/100 and BDE99/100
      in sea ice samples reflect commercial pentaBDE products, suggesting that
      photodegradation of BDE99 is minimal during LRAT in the austral winter.

PMID- 22369051
TI  - A comparative structural bioinformatics analysis of inherited mutations in beta-D
      Mannosidase across multiple species reveals a genotype-phenotype correlation.
AB  - BACKGROUND: Lysosomal beta-D-mannosidase is a glycosyl hydrolase that breaks down
      the glycosidic bonds at the non-reducing end of N-linked glycoproteins. Hence, it
      is a crucial enzyme in polysaccharide degradation pathway. Mutations in the MANBA
      gene that codes for lysosomal beta-mannosidase, result in improper coding and
      malfunctioning of protein, leading to beta-mannosidosis. Studying the location of
      mutations on the enzyme structure is a rational approach in order to understand
      the functional consequences of these mutations. Accordingly, the pathology and
      clinical manifestations of the disease could be correlated to the genotypic
      modifications. RESULTS: The wild-type and inherited mutations of beta-mannosidase
      were studied across four different species, human, cow, goat and mouse employing
      a previously demonstrated comprehensive homology modeling and mutational mapping
      technique, which reveals a correlation between the variation of genotype and the
      severity of phenotype in beta-mannosidosis. X-ray crystallographic structure of
      beta-mannosidase from Bacteroides thetaiotaomicron was used as template for 3D
      structural modeling of the wild-type enzymes containing all the associated
      ligands. These wild-type models subsequently served as templates for building
      mutational structures. Truncations account for approximately 70% of the
      mutational cases. In general, the proximity of mutations to the active site
      determines the severity of phenotypic expressions. Mapping mutations to the MANBA
      gene sequence has identified five mutational hot-spots. CONCLUSION: Although
      restrained by a limited dataset, our comprehensive study suggests a genotype
      phenotype correlation in beta-mannosidosis. A predictive approach for detecting
      likely beta-mannosidosis is also demonstrated where we have extrapolated observed
      mutations from one species to homologous positions in other organisms based on
      the proximity of the mutations to the enzyme active site and their co-location
      from different organisms. Apart from aiding the detection of mutational hotspots
      in the gene, where novel mutations could be disease-implicated, this approach
      also provides a way to predict new disease mutations. Higher expression of the
      exoglycosidase chitobiase is said to play a vital role in determining disease
      phenotypes in human and mouse. A bigger dataset of inherited mutations as well as
      a parallel study of beta-mannosidase and chitobiase activities in prospective
      patients would be interesting to better understand the underlying reasons for
      beta-mannosidosis.

PMID- 22369050
TI  - Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae.
AB  - BACKGROUND: Mammals are not able to restore lost appendages, while many
      amphibians are. One important question about epimorphic regeneration is related
      to the origin of the new tissues and whether they come from mature cells via
      dedifferentiation and/or from stem cells. Several studies in urodele amphibians
      (salamanders) indicate that, after limb or tail amputation, the multinucleated
      muscle fibres do dedifferentiate by fragmentation and proliferation, thereby
      contributing to the regenerate. In Xenopus laevis tadpoles, however, it was shown
      that muscle fibres do not contribute directly to the tail regenerate. We set out
      to study whether dedifferentiation was present during muscle regeneration of the
      tadpole limb and zebrafish larval tail, mainly by cell tracing and histological
      observations. RESULTS: Cell tracing and histological observations indicate that
      zebrafish tail muscle do not dedifferentiate during regeneration. Technical
      limitations did not allow us to trace tadpole limb cells, nevertheless we
      observed no signs of dedifferentiation histologically. However, ultrastructural
      and gene expression analysis of regenerating muscle in tadpole tail revealed an
      unexpected dedifferentiation phenotype. Further histological studies showed that
      dedifferentiating tail fibres did not enter the cell cycle and in vivo cell
      tracing revealed no evidences of muscle fibre fragmentation. In addition, our
      results indicate that this incomplete dedifferentiation was initiated by the
      retraction of muscle fibres. CONCLUSIONS: Our results show that complete skeletal
      muscle dedifferentiation is less common than expected in lower vertebrates. In
      addition, the discovery of incomplete dedifferentiation in muscle fibres of the
      tadpole tail stresses the importance of coupling histological studies with in
      vivo cell tracing experiments to better understand the regenerative mechanisms.

PMID- 22369052
TI  - Development of an ELISA-array for simultaneous detection of five encephalitis
      viruses.
AB  - Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and
      eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis.
      Establishment of accurate and easy methods by which to detect these viruses is
      essential for the prevention and treatment of associated infectious diseases.
      Currently, there are still no multiple antigen detection methods available
      clinically. An ELISA-array, which detects multiple antigens, is easy to handle,
      and inexpensive, has enormous potential in pathogen detection. An ELISA-array
      method for the simultaneous detection of five encephalitis viruses was developed
      in this study. Seven monoclonal antibodies against five encephalitis-associated
      viruses were prepared and used for development of the ELISA-array. The ELISA
      array assay is based on a "sandwich" ELISA format and consists of viral
      antibodies printed directly on 96-well microtiter plates, allowing for direct
      detection of 5 viruses. The developed ELISA-array proved to have similar
      specificity and higher sensitivity compared with the conventional ELISAs. This
      method was validated by different viral cultures and three chicken eggs
      inoculated with infected patient serum. The results demonstrated that the
      developed ELISA-array is sensitive and easy to use, which would have potential
      for clinical use.

PMID- 22369053
TI  - Barriers and facilitators to the use of high-technology augmentative and
      alternative communication devices: a systematic review and qualitative synthesis.
AB  - BACKGROUND: There has been a rapid growth in recent years of available
      technologies for individuals with communication difficulties. Research in the
      area is currently underdeveloped with practitioners having a limited body of work
      on which to draw to guide the process of intervention. Concerns have been raised
      that this newly developed technology may have limited functional usage. AIMS:
      This review aims to investigate the potential barriers and facilitators to high
      technology AAC provision and its ongoing use. The aim of the analysis is to
      explore factors underpinning use rather than effectiveness, thus it synthesized
      data from predominantly qualitative and survey studies reporting the views and
      perceptions of AAC users or staff providing the devices. MAIN CONTRIBUTION: The
      review highlights the range of factors that can impact on provision and use of
      high-technology AAC, which practitioners should consider and address as
      appropriate in the intervention process. These include: ease of use of the
      device; reliability; availability of technical support; voice/language of the
      device; decision-making process; time taken to generate a message; family
      perceptions and support; communication partner responses; service provision; and
      knowledge and skills of staff. The work outlines how qualitative synthesis review
      methods may be applied to the consideration of published material that is not
      reporting outcomes data, and how this may provide valuable information to inform
      future studies. CONCLUSIONS: Practitioners should be aware of barriers and
      facilitators to successful use when making recommendations, and consider how
      barriers where present might be overcome. Aspects of service delivery such as
      ongoing technical support and staff training may require further consideration.
      The synthesis of evidence describing views of users and providers, and the
      implementation of high-technology AAC systems, can provide valuable data to
      inform intervention studies and functional outcome measures.

PMID- 22369054
TI  - Stroke patients communicating their healthcare needs in hospital: a study within
      the ICF framework.
AB  - BACKGROUND: Previous research has identified that many patients admitted into
      acute hospital stroke units have communication-related impairments such as
      hearing, vision, speech, language and/or cognitive communicative impairment.
      However, no research has identified how many patients in acute hospital stroke
      units have difficulty actually communicating their healthcare needs. The World
      Health Organization's International Classification of Functioning, Disability and
      Health (ICF) conceptualizes difficulty communicating about healthcare needs as a
      type of activity limitation, within the Activity and Participation component. The
      ICF proposes that activity limitation can be measured in four different ways.
      AIMS: The first aim of this research was to measure a patient's difficulty
      communicating his or her healthcare needs, that is, activity limitation, in two
      of the four ways suggested by the ICF when interacting with healthcare providers.
      The second aim was to investigate whether communication-related impairments in
      hearing, vision, speech, language and/or cognitive communicative impairment
      predict difficulty communicating healthcare needs, measured in these ways.
      METHODS & PROCEDURES: A total of 65 patients consecutively admitted into two
      acute hospital stroke units in Melbourne, Australia, who consented to this
      research participated in this study. Early in their admission participants were
      screened for hearing, vision, speech, language and cognitive communicative
      impairment. Participants were also assessed for difficulty communicating about
      healthcare needs in two ways proposed by the ICF: 'capacity with assistance' and
      'performance'. Relationships between communication-related impairment and both
      capacity with assistance and performance were explored through Spearman's
      correlations and binary logistic regression. OUTCOMES & RESULTS: A total of 87%
      of patients had one or more communication-related impairments. Half of the
      patients (51%) had difficulty communicating their healthcare needs when assessed
      in terms of capacity with assistance. Slightly more patients (55%) were observed
      to have difficulty communicating their healthcare needs when assessed in terms of
      performance. More severe vision, speech, language and cognitive communicative
      impairment were significantly associated with more severe difficulty
      communicating healthcare needs. CONCLUSIONS & IMPLICATIONS: About half of the
      stroke patients admitted into acute hospital stroke units had difficulty
      communicating their healthcare needs. Patients with more severe communication
      related impairments had more severe difficulty communicating their healthcare
      needs. Future research is needed to understand the other factors that influence
      communication between people with communication disabilities and their healthcare
      providers in acute hospital settings.

PMID- 22369055
TI  - Communication difficulties and the use of communication strategies: from the
      perspective of individuals with aphasia.
AB  - BACKGROUND: To enhance communicative ability and thereby the possibility of
      increased participation of persons with aphasia, the use of communication
      strategies has been proposed. However, little is known about how persons with
      aphasia experience having conversations and how they perceive their own and their
      conversation partner's use of communication strategies. AIMS: To explore how
      people with aphasia experience having conversations, how they handle
      communication difficulties, and how they perceive their own and their
      communication partners' use of communication strategies. METHODS & PROCEDURES:
      Semi-structured interviews were conducted with four women and seven men with
      chronic aphasia (n = 11). Interviews were video-recorded, transcribed verbatim
      and analysed by qualitative content analysis. OUTCOMES & RESULTS: Informants
      appreciated having conversations despite the fact that they perceived their
      aphasia as a serious hindrance. Different factors related to the informants, the
      conversation partners, the conversation itself and the physical environment were
      perceived to impact on conversations. The importance of the communication
      partners' knowledge and understanding of aphasia and their use of supporting
      conversation strategies were acknowledged by the informants. The informants'
      views on using communication aid devices or strategies varied considerably. Four
      themes that characterized the informants' narratives were: loss and frustration,
      fear and uncertainty, shared responsibility based on knowledge, and longing for
      the past or moving forward. CONCLUSIONS & IMPLICATIONS: The informants longed to
      regain their former language ability and role as an active participant in
      society. To enhance participation of persons with aphasia, it is suggested that
      communication partner training should be an important and integral part of
      aphasia rehabilitation. Important elements of such training are reflecting on
      communication behaviours, training in real-life situations, and acknowledging
      each individual's special needs and preferences. To deal with the consequences of
      aphasia, counselling and psychological support may be needed.

PMID- 22369056
TI  - Current evaluation of upper oesophageal sphincter opening in dysphagia practice:
      an international SLT survey.
AB  - BACKGROUND: The assessment of adequate upper oesophageal sphincter (UOS) opening
      during swallowing is an integral component of dysphagia evaluation. AIMS: To
      ascertain speech and language therapists' (SLTs) satisfaction with current
      methods for assessing UOS function in people with dysphagia and to identify
      challenges encountered by SLTs with UOS evaluation. METHODS & PROCEDURES: A
      survey was disseminated to 82 SLT managers in Ireland; to two dysphagia Special
      Interest Groups in the UK; and to the Royal College of Speech & Language
      Therapists'Bulletin periodical. A survey link was also posted on the American
      Speech and Hearing Association (ASHA) Division 13 (Dysphagia) web forum. OUTCOMES
      & RESULTS: Surveys from 224 SLTs with active dysphagia caseloads were included in
      data analysis. Only 17.9% (40/224) of SLTs were satisfied with the accuracy and
      reliability of UOS evaluations currently being employed in dysphagia practice.
      Satisfaction with current UOS evaluation was not associated with the level of
      clinical experience (r= 0.078; p= 0.246). Eighty-seven per cent (195/224) of SLTs
      working with dysphagia experience challenges in UOS evaluation. Challenges
      reported include lack of resources/equipment (55.9%), limited quantitative
      information (45.6%), lack of training (41%) and knowledge (39%) in UOS function,
      and limited multidisciplinary team involvement (34%). CONCLUSIONS & IMPLICATIONS:
      SLTs across all levels of clinical experience are not satisfied with current UOS
      evaluation in dysphagia practice. Based on the specific challenges identified,
      recommendations to progress SLT evaluation of UOS function in people with
      dysphagia are proposed.

PMID- 22369057
TI  - Investigating sentence processing and language segmentation in explaining
      children's performance on a sentence-span task.
AB  - BACKGROUND: Children with poor language abilities tend to perform poorly on
      verbal working memory tasks. This result has been interpreted as evidence that
      limitations in working memory capacity may interfere with the development of a
      mature linguistic system. However, it is possible that language abilities, such
      as the efficiency of sentence processing and the ability to segment language,
      directly influence performance on common working memory tasks. AIMS: This study
      investigated the possible roles of sentence-processing efficiency and the ability
      to segment language in children's performance on a verbal working memory task.
      METHODS & PROCEDURES: Participants were 37 children (aged 6;2-13;7) with varying
      oral language and reading abilities. Children completed a sentence-span task to
      assess working memory: the Competing Language Processing Task (CLPT). In the
      CLPT, children determine the truth value of sentences while maintaining sentence
      final words in memory. Sentence-processing efficiency was evaluated by measuring
      response latencies to CLPT sentence veracity judgments outside the context of the
      CLPT. The Elision and Blending Words subtests of the Comprehensive Test of
      Phonological Processing were used to measure the ability to segment and combine
      units of language. OUTCOMES & RESULTS: Children's ability to segment words into
      smaller units (Elision) was a significant predictor of word recall on the CLPT,
      which is commonly assumed to reflect working memory capacity. Sentence processing
      latency did not reach significance as a unique predictor. CONCLUSIONS &
      IMPLICATIONS: Individual differences on the sentence-span task are partly
      explained by the ability to segment language into smaller units. Future studies
      should further consider the metalinguistic and metacognitive demands of tasks
      used to measure working memory. If metalinguistic abilities directly impact
      performance on working memory tasks, the utility of working memory theories in
      explaining individual differences in language abilities is reduced. Inferences
      that link 'working memory capacity' to language ability become circular. One
      clinical implication of such a result would be that appropriate intervention
      strategies may not involve focusing on working memory capacity, but rather on
      building language skills, including metalinguistic knowledge, which in turn
      should directly improve children's processing capacities.

PMID- 22369058
TI  - Linguistic transfer in bilingual children with specific language impairment.
AB  - BACKGROUND: In the literature so far the limited research on specific language
      impairment (SLI) in bilingual children has concentrated on linguistic skills in
      the first language (L1) and/or the second language (L2) without paying attention
      to the relations between the two types of skills and to the issue of linguistic
      transfer. AIMS: To examine the first and second language proficiency of 75
      Turkish-Dutch bilingual children with SLI in the age range between 7 and 11 years
      living in the Netherlands. A multidimensional perspective on language proficiency
      was taken in order to assess children's Turkish and Dutch proficiency levels,
      whereas equivalent tests were used in order to determine language dominance. A
      second aim was to find out to what extent the children's proficiency in L2 can be
      predicted from their L1 proficiency, while taking into account their general
      cognitive abilities. METHODS & PROCEDURES: The children's performance on a
      battery of equivalent language ability tests in Turkish and Dutch was compared at
      three age levels. By means of analyses of variance, it was explored to what
      extent the factors of language and grade level as well as their interactions were
      significant. Bivariate correlations and partial correlations with age level
      partialled out were computed to examine the relationships between L1 and L2
      proficiency levels. Moreover, regression analysis was conducted to find out to
      what extent the variance in general L2 proficiency levels could be explained by
      children's L1 proficiency, short-term memory and non-verbal intelligence.
      OUTCOMES & RESULTS: Repeated measures analyses showed that the children had
      generally higher scores on L1 as compared with L2 and that with progression of
      age the children's scores in L1 and L2 improved. Medium to high correlations were
      found between phonological memory, phonological awareness, grammatical skills and
      story comprehension in the two languages. Regression analysis revealed that
      children's L2 proficiency levels could be explained by their proficiency levels
      in L1, even after controlling for children's non-verbal intelligence and working
      memory. CONCLUSIONS & IMPLICATIONS: It is concluded that children's formal
      linguistic skills in L1 and L2 tend to be related and that their level of L1
      proficiency may help to develop linguistic skills in L2.

PMID- 22369059
TI  - Perceptions of parents and speech and language therapists on the effects of
      paediatric cochlear implantation and habilitation and education following it.
AB  - BACKGROUND: During the process of implantation, parents may have rather
      heterogeneous expectations and concerns about their child's development and the
      functioning of habilitation and education services. Their views on habilitation
      and education are important for building family-centred practices. AIMS: We
      explored the perceptions of parents and speech and language therapists (SLTs) on
      the effects of implantation on the child and the family and on the quality of
      services provided. Their views were also compared. METHODS & PROCEDURES: Parents
      and SLTs of 18 children filled out questionnaires containing open- and closed
      ended questions at 6 months and annually 1-5 years after activation of the
      implant. Their responses were analysed mainly using data-based inductive content
      analysis. OUTCOMES & RESULTS: Positive experiences outnumbered negative ones in
      the responses of both the parents and the SLTs surveyed. The parents were
      particularly satisfied with the improvement in communication and expanded social
      life in the family. These were the most prevalent themes also raised by the SLTs.
      The parents were also satisfied with the organization and content of
      habilitation. Most of the negative experiences were related to arrangement of
      hospital visits and the usability and maintenance of speech processor technology.
      Some children did not receive enough speech and language therapy, and some of the
      parents were dissatisfied with educational services. The habilitation process had
      generally required parental efforts at an expected level. However, parents with a
      child with at least one concomitant problem experienced habilitation as more
      stressful than did other parents. CONCLUSIONS & IMPLICATIONS: Parents and SLTs
      had more positive than negative experiences with implantation. As the usability
      and maintenance of speech processor technology were often compromised, we urge
      implant centres to ensure sufficient personnel for technical maintenance. It is
      also important to promote services by providing enough information and parental
      support.

PMID- 22369060
TI  - Narrative skill and syntactic complexity in school-age children with and without
      late language emergence.
AB  - BACKGROUND: Children who do not produce single words by the expected age have
      been described as 'late talkers' or as demonstrating 'late language emergence'
      (LLE). Although their short-term growth in vocabulary is often strong, longer
      term consequences of LLE remain in dispute. It has been argued that the majority
      of school-age children who had LLE move into the average range for narrative
      production, though studies have not examined narrative comprehension. It has also
      been argued that school-age children with LLE score in the average range on
      standardized tests of syntax, though studies have not examined performance in
      conversational contexts. AIMS: This article compared school-age children with and
      without histories of LLE for performance on standardized narrative comprehension
      and production tasks, as well as the use of complex sentences and relative
      clauses in narration and conversation. Both complex syntax and relative clause
      use are reduced in children with specific language impairment (SLI), so these
      structures may be useful as indicators of linguistic weakness. METHODS &
      PROCEDURES: The participants were twenty-two 8-year-old children, divided into
      two groups. Eleven children who had been diagnosed with LLE at 30 months were
      compared with a control group of 11 children with typical development (TD). All
      participants completed a standardized test of narrative comprehension and
      production and a 10-min conversational sample. Both narrative and conversational
      samples were analysed for the number of complex sentences and relative clauses.
      OUTCOMES & RESULTS: Overall results indicated that children with a history of LLE
      did not have comprehension or production scores that were significantly different
      from the TD group on the standardized narrative test; nor did groups differ for
      production of complex sentences or relative clauses in narrative samples.
      However, a significant difference was found for the production of complex
      sentences in conversational samples, with the children diagnosed with LLE
      producing fewer complex sentences than the TD group. There was no difference
      between groups for relative clause use in conversation or in narratives.
      CONCLUSIONS & IMPLICATIONS: These data suggest that children with a history of
      LLE may exhibit age-appropriate performance on a standardized narrative test, but
      still lack the syntactic complexity of their TD peers in conversation.
      Assessments for school-age children with a history of language delay should
      include analysis of syntactic complexity in conversation to identify continuing
      weakness. Future research should examine use of other specific types of complex
      structures (e.g. infinitival and clausal complements) in this population, as well
      the feasibility of increasing complex sentence production through intervention.
      In addition, future studies should examine whether this decreased production of
      complex syntax in conversation is noted by naive listeners.

PMID- 22369061
TI  - Influence of additional language learning on first language learning in children
      with language disorders.
AB  - BACKGROUND: Multilingualism can bring about various positive outcomes to
      typically developing children. Its effect on children with language difficulties
      is not yet clear. AIM: The aim of this study was to examine the effects of
      multilingual learning as a medium of instruction (MOI) on first language (L1)
      acquisition of children with language disorders (LD). METHODS & PROCEDURES:
      Nineteen Cantonese-speaking students aged 5;8-6;8 who were diagnosed with LD were
      recruited from a school that used Putonghua (an alternative Chinese dialect) as
      the MOI when learning Chinese language and were compared with 18 age-and-gender
      matched Cantonese-speaking students with LD from a school that used Cantonese as
      the MOI when learning Chinese language. All the students also learned English
      (L2) as a subject at school. Proficiency in Cantonese was tested at the beginning
      and the end of the semester in Grade One in terms of: (1) grammar, (2) expressive
      vocabulary, (3) auditory textual comprehension, (4) word definition and (5)
      narration. OUTCOMES & RESULTS: Mixed-model ANOVAs revealed an effect of time on
      language proficiency indicating positive gains in both groups. Interaction
      effects between time and group were not significant. There was a trend that
      children learning Putonghua showed slightly more improvement in auditory textual
      comprehension. CONCLUSIONS & IMPLICATIONS: Proficiency gains were similar across
      groups. The study found no evidence that a multilingual learning environment
      hinders the language proficiency in L1 in students who have LD.

PMID- 22369062
TI  - The messages they send: e-mail use by adolescents with and without a history of
      specific language impairment (SLI).
AB  - BACKGROUND: Contemporary adolescents use e-mail for a variety of purposes,
      including peer communication and education. Research into these uses has focused
      on typically developing individuals; much less is known about the use of e-mail
      by exceptional youth. AIMS: The present study examined the structure and form of
      e-mail messages sent by adolescents with and without a history of specific
      language impairment (SLI). METHODS & PROCEDURES: Thirty-eight adolescents with a
      history of SLI and 56 typically developing (TD) peers were assessed on measures
      of nonverbal abilities, core language skills and literacy skills (reading and
      spelling). The participants were asked to compose an e-mail reply to a standard e
      mail sent by an experimenter. These reply e-mails were coded for linguistic
      structure, readability and spelling errors. Two adult raters, blind to the
      participants' language ability, judged how understandable the e-mails were, how
      grammatically correct the e-mails were, and also the sender's command of the
      English language. OUTCOMES & RESULTS: Adolescents with a history of SLI produced
      e-mails that were similar to those sent by their TD peers in terms of structure
      and readability. However, they made significantly more spelling errors.
      Furthermore, the adult raters considered the messages from participants with a
      history of SLI to be of poorer standard than those sent by their TD peers.
      CONCLUSIONS & IMPLICATIONS: The findings suggest that the e-mail messages of
      adolescents with a history of SLI provide indicators of the sender's language and
      literacy skills. Implications for intervention and technology development are
      discussed.

PMID- 22369063
TI  - Copper redistribution in murine macrophages in response to Salmonella infection.
AB  - The movement of key transition metal ions is recognized to be of critical
      importance in the interaction between macrophages and intracellular pathogens.
      The present study investigated the role of copper in mouse macrophage responses
      to Salmonella enterica sv. Typhimurium. The copper chelator BCS
      (bathocuproinedisulfonic acid, disodium salt) increased intracellular survival of
      S. Typhimurium within primary mouse BMM (bone-marrow-derived macrophages) at 24 h
      post-infection, implying that copper contributed to effective host defence
      against this pathogen. Infection of BMM with S. Typhimurium or treatment with the
      TLR (Toll-like receptor) 4 ligand LPS (lipopolysaccharide) induced the expression
      of several genes encoding proteins involved in copper transport [Ctr (copper
      transporter) 1, Ctr2 and Atp7a (copper-transporting ATPase 1)], as well as the
      multi-copper oxidase Cp (caeruloplasmin). Both LPS and infection with S.
      Typhimurium triggered copper accumulation within punctate intracellular vesicles
      (copper 'hot spots') in BMM as indicated by the fluorescent reporter CS1 (copper
      sensor 1). These copper hot spots peaked in their accumulation at approximately
      18 h post-stimulation and were dependent on copper uptake into cells.
      Localization studies indicated that the copper hot spots were in discrete
      vesicles distinct from Salmonella containing vacuoles and lysosomes. We propose
      that copper hot spot formation contributes to antimicrobial responses against
      professional intracellular bacterial pathogens.

PMID- 22369064
TI  - The contribution of extramedullary hematopoiesis to hepatomegaly in anemic
      hydrops fetalis: a study in alpha-thalassemia hydrops fetalis.
AB  - Massive hepatomegaly is a common finding in hydrops fetalis (HF) arising from
      hemoglobinopathies. It has been suggested that extramedullary hematopoiesis,
      which is markedly increased in response to anemia, plays a principal role in
      hepatomegaly via sinusoidal obstruction and distortion of the intrahepatic
      architecture. To test this concept, the authors compared 20 cases of alpha
      thalassemia (hemoglobin Bart, 15 cases; hemoglobin H, 5 cases) with 19 cases of
      HF arising from other causes and 39 control nonhydrops cases. The mean liver
      weight in alpha-thalassemia cases was significantly heavier than in control cases
      and in hydrops fetalis cases due to other causes (P < 0.01). This was not
      explainable on the basis of extramedullary hematopoiesis (erythropoiesis or
      myelopoiesis) or hemosiderin deposition, since cases of HF from other causes,
      especially related to anemia, showed similar findings to alpha-thalassemia cases.
      While these processes no doubt contribute to hepatic weight, the major factor
      would still be high-output cardiac failure causing hepatic congestion.

PMID- 22369065
TI  - Emu Oil: a novel therapeutic for disorders of the gastrointestinal tract?
AB  - Gastrointestinal diseases characterized by inflammation, including the
      inflammatory bowel diseases, chemotherapy-induced mucositis and non-steroidal
      anti-inflammatory drug-induced enteropathy, currently have variably effective
      treatment options, highlighting the need for novel therapeutic approaches.
      Recently, naturally-sourced agents including prebiotics, probiotics, plant
      extracts and marine-derived oils known to possess anti-inflammatory and anti
      oxidant properties have been investigated in vitro and in vivo. However, animal
      derived oils are yet to be extensively tested. Emu Oil is extracted from the
      subcutaneous and retroperitoneal fat of the Emu, a flightless bird native to
      Australia, and predominantly comprises fatty acids. Despite the limited rigorous
      scientific studies conducted to date, with largely anecdotal claims, Emu Oil,
      when administered topically and orally, has been shown to possess significant
      anti-inflammatory properties in vivo. These include a CD-1 mouse model of croton
      oil-induced auricular inflammation, experimentally-induced polyarthritis and
      dextran sulfate sodium-induced colitis. Recently, Emu Oil has been demonstrated
      to endow partial protection against chemotherapy-induced mucositis, with early
      indications of improved intestinal repair. Emu Oil could therefore form the basis
      of an adjunct to conventional treatment approaches for inflammatory disorders
      affecting the gastrointestinal system.

PMID- 22369066
TI  - Detoxification of H(2)S by differentiated colonic epithelial cells: implication
      of the sulfide oxidizing unit and of the cell respiratory capacity.
AB  - AIMS: Sulfide is released in the large intestine lumen by the microbiota and is
      an inhibitor of mitochondrial respiration and a genotoxic agent in colonocytes
      when present in excess. Deciphering how colonocytes metabolize sulfide is an
      important issue. RESULTS: In this study, using the human colonic epithelial HT-29
      Glc(-/+) cells, we found that 50 MUM sodium hydrogen sulfide represents the
      threshold of concentration above which respiration is decreased. The capacity of
      HT-29 Glc(-/+) cells to oxidize lower concentration of sulfide was associated
      with the expression of transcripts corresponding to the enzymes of the sulfide
      oxidizing unit (SOU), that is, sulfide quinone reductase (SQR), dioxygenase
      ethylmalonic encephalopathy, and thiosulfate sulfur transferase (TST). Inhibition
      of cell O(2) consumption by sulfide was reverted by zinc but not by calcium and
      iron. When the cells undergo either spontaneous or butyrate-induced
      differentiation, their capacity to oxidize sulfide was significantly increased.
      The expression levels of the genes corresponding to the enzymes of the SOU were
      not increased, whereas increased cellular maximal respiratory capacity and oxygen
      consumption by the dioxygenase were both measured. In human biopsies recovered
      from various parts of the large intestine, the three enzymes of the SOU were
      expressed. INNOVATION: SOU and cell respiratory capacity are crucial for sulfide
      detoxification in colonocytes. CONCLUSION: Sulfide oxidative capacity in the
      colonic mucosa is higher in differentiated than in proliferative epithelial
      cells. The cell respiratory capacity and SOU activity appear to represent major
      determinants allowing sulfide detoxification in colonic epithelial cells.

PMID- 22369067
TI  - Surface plasmon resonance properties of single elongated nano-objects: gold
      nanobipyramids and nanorods.
AB  - The spectral characteristics (wavelength and line width) and the optical
      extinction cross-section of the longitudinal localized surface plasmon resonance
      (LSPR) of individual gold nanobipyramids have been quantitatively measured using
      the spatial modulation spectroscopy technique. The morphology of the same
      individual nanoparticles has been determined by transmission electron microscopy
      (TEM). The experimental results are thus interpreted with a numerical model using
      the TEM measured sizes of the particles as an input, and either including the
      substrate or assuming a mean homogeneous environment. Results are compared to
      those obtained for individual nanorods and also show the importance of the local
      environment of the particle on the detailed description of its spectral position
      and extinction amplitude.

PMID- 22369068
TI  - Sorghum phenolics demonstrate estrogenic action and induce apoptosis in
      nonmalignant colonocytes.
AB  - Evidence indicates sorghum may be protective against colon cancer; however, the
      mechanisms are unknown. Estrogen is believed to protect against colon cancer
      development by inducing apoptosis in damaged nonmalignant colonocytes. Three
      sorghum extracts (white, red, and black) were screened for estrogenic activity
      using cell models expressing estrogen receptor alpha (ER-alpha; MCF-7 breast
      cancer cells) and beta [ER-beta; nonmalignant young adult mouse colonocytes
      (YAMC)]. Black and white sorghum extracts had significant estrogenic activity
      mediated through both estrogen receptors at 1-5 and 5-10 MUg/mL, respectively;
      but red sorghum did not. Activation of ER-beta in YAMC reduced cell growth via
      induction of apoptosis. Only the black and red sorghums contained 3
      deoxyanthocyanins; however, these compounds were non-estrogenic. Flavones with
      estrogenic properties, luteolin (0.41-2.12 mg/g) and apigenin (1.1-1.4 mg/g), and
      their O-methyl derivatives (0.70-0.95 mg/g) were detected in white and black
      sorghums, but not in the red sorghum. On the other hand, naringenin, a flavanone
      known to interfere with transcriptional activities of estrogen, was only detected
      in the red sorghum extract (as its 7-O-glycoside) at relatively high
      concentration (11.8 mg/g). Sorghum flavonoid composition has important
      implications on possible modes of chemoprotection by sorghum against colon
      carcinogenesis.

PMID- 22369070
TI  - Parallel progressive multiple sequence alignment on reconfigurable meshes.
AB  - BACKGROUND: One of the most fundamental and challenging tasks in bio-informatics
      is to identify related sequences and their hidden biological significance. The
      most popular and proven best practice method to accomplish this task is aligning
      multiple sequences together. However, multiple sequence alignment is a computing
      extensive task. In addition, the advancement in DNA/RNA and Protein sequencing
      techniques has created a vast amount of sequences to be analyzed that exceeding
      the capability of traditional computing models. Therefore, an effective parallel
      multiple sequence alignment model capable of resolving these issues is in a great
      demand. RESULTS: We design O(1) run-time solutions for both local and global
      dynamic programming pair-wise alignment algorithms on reconfigurable mesh
      computing model. To align m sequences with max length n, we combining the
      parallel pair-wise dynamic programming solutions with newly designed parallel
      components. We successfully reduce the progressive multiple sequence alignment
      algorithm's run-time complexity from O(m * n4) to O(m) using O(m * n3) processing
      units for scoring schemes that use three distinct values for match/mismatch/gap
      extension. The general solution to multiple sequence alignment algorithm takes
      O(m * n4) processing units and completes in O(m) time. CONCLUSIONS: To our
      knowledge, this is the first time the progressive multiple sequence alignment
      algorithm is completely parallelized with O(m) run-time. We also provide a new
      parallel algorithm for the Longest Common Subsequence (LCS) with O(1) run-time
      using O(n3) processing units. This is a big improvement over the current best
      constant-time algorithm that uses O(n4) processing units.

PMID- 22369071
TI  - Learning generative models of molecular dynamics.
AB  - We introduce three algorithms for learning generative models of molecular
      structures from molecular dynamics simulations. The first algorithm learns a
      Bayesian-optimal undirected probabilistic model over user-specified covariates
      (e.g., fluctuations, distances, angles, etc). L1 regularization is used to ensure
      sparse models and thus reduce the risk of over-fitting the data. The topology of
      the resulting model reveals important couplings between different parts of the
      protein, thus aiding in the analysis of molecular motions. The generative nature
      of the model makes it well-suited to making predictions about the global effects
      of local structural changes (e.g., the binding of an allosteric regulator).
      Additionally, the model can be used to sample new conformations. The second
      algorithm learns a time-varying graphical model where the topology and parameters
      change smoothly along the trajectory, revealing the conformational sub-states.
      The last algorithm learns a Markov Chain over undirected graphical models which
      can be used to study and simulate kinetics. We demonstrate our algorithms on
      multiple molecular dynamics trajectories.

PMID- 22369072
TI  - Fifty years after thalidomide; what role for drug regulators?

PMID- 22369074
TI  - Contribution of lubricating oil to particulate matter emissions from light-duty
      gasoline vehicles in Kansas City.
AB  - The contribution of lubricating oil to particulate matter (PM) emissions
      representative of the in-use 2004 light-duty gasoline vehicles fleet is estimated
      from the Kansas City Light-Duty Vehicle Emissions Study (KCVES). PM emissions are
      apportioned to lubricating oil and gasoline using aerosol-phase chemical markers
      measured in PM samples obtained from 99 vehicles tested on the California Unified
      Driving Cycle. The oil contribution to fleet-weighted PM emission rates is
      estimated to be 25% of PM emission rates. Oil contributes primarily to the
      organic fraction of PM, with no detectable contribution to elemental carbon
      emissions. Vehicles are analyzed according to pre-1991 and 1991-2004 groups due
      to differences in properties of the fitting species between newer and older
      vehicles, and to account for the sampling design of the study. Pre-1991 vehicles
      contribute 13.5% of the KC vehicle population, 70% of oil-derived PM for the
      entire fleet, and 33% of the fuel-derived PM. The uncertainty of the
      contributions is calculated from a survey analysis resampling method, with 95%
      confidence intervals for the oil-derived PM fraction ranging from 13% to 37%. The
      PM is not completely apportioned to the gasoline and oil due to several
      contributing factors, including varied chemical composition of PM among vehicles,
      metal emissions, and PM measurement artifacts. Additional uncertainties include
      potential sorption of polycyclic aromatic hydrocarbons into the oil,
      contributions of semivolatile organic compounds from the oil to the PM
      measurements, and representing the in-use fleet with a limited number of
      vehicles.

PMID- 22369073
TI  - Acetylcholinesterase inhibitors attenuate angiogenesis.
AB  - Donepezil {(RS)-2-[(1-benzyl-4-piperidyl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1
      one} is a reversible acetylcholinesterase inhibitor and used for treatment of
      patients with AD (Alzheimer's disease). Recent studies showed that treatment with
      donepezil reduced production of inflammatory cytokines in PBMCs (peripheral blood
      mononuclear cells). It was also reported that muscle-derived inflammatory
      cytokines play a critical role in neovascularization in a hindlimb ischaemia
      model. We sought to determine whether donepezil affects angiogenesis. A hindlimb
      ischaemia model was created by unilateral femoral artery ligation. Blood flow
      recovery examined by laser Doppler perfusion imaging and capillary density by
      immunohistochemical staining of CD31-positive cells in the ischaemic hindlimb
      were significantly decreased in donepezil- and physostigmine-treated mice
      compared with control mice after 2 weeks. Donepezil reduced expression of IL
      (interleukin)-1beta and VEGF (vascular endothelial growth factor) in the
      ischaemic hindlimb. Intramuscular injections of IL-1beta to the ischaemic
      hindlimb reversed the donepezil-induced VEGF down-regulation and the anti
      angiogenic effect. Hypoxia induced IL-1beta expression in C2C12 myoblast cells,
      which was inhibited by pre-incubation with ACh (acetylcholine) or LY294002, a
      PI3K (phosphoinositide 3-kinase) inhibitor. Donepezil inhibited phosphorylation
      of Akt [also known as PKB (protein kinase B)], a downstream kinase of PI3K, in
      the ischaemic hindlimb. These findings suggest that cholinergic stimulation by
      acetylcholinesterase inhibitors suppresses angiogenesis through inhibition of
      PI3K-mediated IL-1beta induction, which is followed by reduction of VEGF
      expression. Acetylcholinesterase inhibitor may be a novel anti-angiogenic
      therapy.

PMID- 22369075
TI  - A centronuclear myopathy--dynamin 2 mutation impairs autophagy in mice.
AB  - Dynamin 2 (Dnm2) is involved in endocytosis and intracellular membrane
      trafficking through its function in vesicle formation from distinct membrane
      compartments. Heterozygous (HTZ) mutations in the DNM2 gene cause dominant
      centronuclear myopathy or Charcot-Marie-Tooth neuropathy. We generated a knock-in
      Dnm2R465W mouse model expressing the most frequent human mutation and recently
      reported that HTZ mice progressively developed a myopathy. We investigated here
      the cause of neonatal lethality occurring in homozygous (HMZ) mice. We show that
      HMZ mice present at birth with a reduced body weight, hypoglycemia, increased
      liver glycogen content and hepatomegaly, in agreement with a defect in neonatal
      autophagy. In vitro studies performed in HMZ embryonic fibroblasts point out to a
      decrease in the autophagy flux prior to degradation at the autolysosome. We show
      that starved HMZ cells have a higher number of immature autophagy-related
      structures probably due to a defect of acidification. Our results highlight the
      role of Dnm2 in the cross talk between endosomal and autophagic pathways and
      evidence a new role of Dnm2-dependent membrane trafficking in autophagy which may
      be relevant in DNM2-related human diseases.

PMID- 22369076
TI  - Introduction to the special section on ethical issues in clinical writing.
AB  - This introduction provides an overview of the special section on ethical issues
      in clinical writing. A summary of the complex issues presented by the author of
      the lead article (Barbara Sieck), and the four authors who were invited to
      respond to the paper (Jeffrey Barnett, Mark Blechner, Constance Fischer, and
      Susan Woodhouse), is followed by a critique of instructions to authors about
      ethical standards included in Psychotherapy and other journals. It is recommended
      that journal editorial boards regularly review policies regarding ethical
      standards about published case material. The introduction concludes with
      Psychotherapy's newly revised instructions to authors submitting clinical
      manuscripts, which now require more specific information about how ethical
      guidelines were applied.

PMID- 22369077
TI  - Confidentiality: against disguise, for consent.
AB  - I am in favor of asking patients for permission to publish clinical material
      about them, but am against disguising clinical material. Altering facts to
      disguise a patient's identity is like publishing false scientific data. Instead,
      details should be omitted unless they are crucial. While there are quite a few
      reports of patients who were offended by publications with their clinical
      material, some patients may be offended if the clinician does not use their
      material. Whatever the procedure for requesting consent, the tone and mindset of
      the therapist are critical. There must be clarity, in the clinician's mind and
      communications, that the patient can refuse consent with no adverse consequences.

PMID- 22369078
TI  - Comments on protecting clients about whom we write (and speak).
AB  - This comment lauds Barbara Sieck's article ("Obtaining clinical writing informed
      consent versus using client disguise and recommendations for practice",
      Psychotherapy, 49, pp. 3-11.) as a solid review not only for therapists but for
      all clinicians and researchers. Her review also is relevant for assorted spoken
      presentations and for presentation of psychological assessment excerpts/reports,
      film clips, and qualitative research data and findings. Procedures that promote
      adequate disguise are listed, with an emphasis on the importance of authentically
      engaging the person-to-be-presented in discussion of the intended
      audience/readers and of what is being illustrated. The latter step serves not
      only the integrity of the participant but also their sense of contributing and of
      being respected.

PMID- 22369079
TI  - Clinical writing: additional ethical and practical issues.
AB  - The recommendations by Sieck (2011, Obtaining clinical writing informed consent
      versus using client disguise and recommendations for practice, Psychotherapy, 49,
      pp. 3-11.) are a helpful starting point for considering the ethical issues
      involved in the decision to seek or not to seek informed consent from clients
      before writing about them. Sieck makes a compelling case for the idea that there
      are circumstances in which the most ethical choice would be to engage in clinical
      writing about a client without seeking informed consent, but instead disguising
      the client's identity. The present response raises a number of questions not
      considered in the article by Sieck. First, how should one disguise a case?
      Moreover, how should one assess whether the disguise is sufficient to preserve
      confidentiality while not distorting the clinical material to the point that the
      material is no longer useful to the field? Second, how can we estimate the
      likelihood of clients reading clinical writing, particularly in the age of the
      Internet? Given that psychologist-authored blogs that include reference to
      clinical material are beginning to emerge, it is crucial that we engage in a much
      deeper dialogue about the ethics of clinical writing. Third, how does the
      presentation of clinical material influence public perceptions of psychotherapy
      and confidentiality? If these public perceptions, in turn, could influence the
      likelihood of seeking psychotherapy, might these attitudes be important to
      consider in ethical thinking about clinical writing? Finally, where do we draw
      the line between clinical writing and single case study research (which requires
      informed consent)?

PMID- 22369080
TI  - Alliance rupture and repair in conjoint family therapy: an exploratory study.
AB  - In this article, we introduce a methodology for studying alliance rupture and
      repair in conjoint family therapy. Using the System for Observing Family Therapy
      Alliances (Friedlander, Escudero, & Heatherington, 2006), we identified rupture
      markers and repair interventions in a session with a single mother and her 16
      year-old "rebellious" daughter. The session was selected for analysis because a
      severe rupture was clinically evident; however, by the end of the session, there
      was an emotional turnaround, which was sustained in the following session and
      continued until the successful, mutually agreed upon termination. The first
      rupture occurred when the psychotherapist suggested that the mother explore, in
      an individual session, how her "personal stress" may be affecting her daughter.
      The observational analysis showed repeated rupture markers, that is,
      confrontation and withdrawal behavior, hostile within-family interactions, and a
      seriously "split" alliance in family members' expressed feelings toward the
      psychotherapist. The time-stamped behavioral stream showed that the
      psychotherapist focused first on safety, then on enhancing his emotional
      connection with each client, and finally on helping mother and daughter
      understand each other's behavior and recognize their shared isolation.

PMID- 22369081
TI  - Collaborative assessment and management of suicidality in an inpatient setting:
      results of a pilot study.
AB  - Patients hospitalized for psychiatric reasons exhibit significantly elevated risk
      of suicide, yet the research literature contains very few outcome studies of
      interventions designed for suicidal inpatients. This pilot study examined the
      inpatient feasibility and effectiveness of The Collaborative Assessment and
      Management of Suicidality (CAMS), a structured evidence-based method for risk
      assessment and treatment planning (Jobes, 2006). The study used an open-trial,
      case-focused design to assess an inpatient adaptation of CAMS, spread over a
      period averaging 51 days. The intervention was provided via individual therapy to
      a convenience sample of 20 patients (16 females and four males, average age 36.9)
      who were hospitalized with recent histories of suicidal ideation and behavior.
      Results showed statistically and clinically significant reductions in depression,
      hopelessness, suicide cognitions, and suicidal ideation, as well as improvement
      on factors considered "drivers" of suicidality. Treatment effect sizes were in
      the large range (Cohen's d > .80) across several outcome measures, including
      suicidal ideation. Although these findings must be considered preliminary due to
      the lack of a randomized control group, they merit attention from clinicians
      working with patients at risk for suicide. This study also supports the
      feasibility of implementing a structured, suicide-specific intervention for at
      risk patients in inpatient settings.

PMID- 22369082
TI  - Suicide risk assessment in clinical practice: pragmatic guidelines for imperfect
      assessments.
AB  - This practice review focuses on the challenges of conducting sensitive and
      accurate assessments of the relative risk for suicide attempts and completed
      suicides. Suicide and suicide attempts are a frequently encountered clinical
      crisis, and the assessment, management, and treatment of suicidal patients is one
      of the most stressful tasks for clinicians. An array of risk factors, warning
      signs, and protective factors associated with suicide risk are reviewed; however,
      we are not yet in possession of evidence-based diagnostic tests that can
      accurately predict suicide risk on an individual level without also creating an
      inordinate number of false-positive predictions. Given the current limitations of
      assessment strategies, clinicians are advised to keep in mind that patients
      contemplating suicide are under enormous psychological distress, requiring
      sensitive and thoughtful engagement during the assessment process. An overarching
      goal of these assessments should be conducted within the therapeutic frame, in
      which efforts are made to enhance the therapeutic alliance by negotiating a
      collaborative approach to assessing risk and understanding why thoughts of
      suicide are so compelling. Within this treatment heuristic, the Suicide
      Assessment Five-step Evaluation and Triage (SAFE-T) is recommended as a pragmatic
      multidimensional assessment protocol incorporating the best known risk and
      protective factors.

PMID- 22369085
TI  - The expression of spinal methyl-CpG-binding protein 2, DNA methyltransferases and
      histone deacetylases is modulated in persistent pain states.
AB  - BACKGROUND: DNA CpG methylation is carried out by DNA methyltransferases and
      induces chromatin remodeling and gene silencing through a transcription repressor
      complex comprising the methyl-CpG-binding protein 2 (MeCP2) and a subset of
      histone deacetylases. Recently, we have found that MeCP2 activity had a crucial
      role in the pattern of gene expression seen in the superficial dorsal horn
      rapidly after injection of Complete Freund's Adjuvant (CFA) in the rat ankle
      joint. The aim of the present study was to analyse the changes in expression of
      MeCP2, DNA methyltransferases and a subset of histone deacetylases in the
      superficial dorsal horn during the maintenance phase of persistent pain states.
      In this process, the cell specific expression of MeCP2 was also investigated.
      RESULTS: Using immunohistochemistry, we found that neurones, oligodendrocytes and
      astrocytes expressed MeCP2. Microglia, oligodendrocyte precursor cells and
      Schwann cells never showed any positive stain for MeCP2. Quantitative analyses
      showed that MeCP2 expression was increased in the superficial dorsal horn 7 days
      following CFA injection in the ankle joint but decreased 7 days following spared
      nerve injury. Overall, the expression of DNA methyltransferases and a subset of
      histone deacetylases followed the same pattern of expression. However, there were
      no significant changes in the expression of the MeCP2 targets that we had
      previously shown are regulated in the early time points following CFA injection
      in the ankle joint. Finally, the expression of MeCP2 was also down regulated in
      damaged dorsal root ganglion neurones following spared nerve injury. CONCLUSION:
      Our results strongly suggest that changes in chromatin compaction, regulated by
      the binding of MeCP2 complexes to methylated DNA, are involved in the modulation
      of gene expression in the superficial dorsal horn and dorsal root ganglia during
      the maintenance of persistent pain states.

PMID- 22369086
TI  - Genetic copy number variants in myocardial infarction patients with
      hyperlipidemia.
AB  - BACKGROUND: Cardiovascular disease is the chief cause of death in Taiwan and many
      countries, of which myocardial infarction (MI) is the most serious condition.
      Hyperlipidemia appears to be a significant cause of myocardial infarction,
      because it causes atherosclerosis directly. In recent years, copy number
      variation (CNV) has been analyzed in genomewide association studies of complex
      diseases. In this study, CNV was analyzed in blood samples and SNP arrays from 31
      myocardial infarction patients with hyperlipidemia. RESULTS: We identified seven
      CNV regions that were associated significantly with hyperlipidemia and myocardial
      infarction in our patients through multistage analysis (P<0.001), at 1p21.3,
      1q31.2 (CDC73), 1q42.2 (DISC1), 3p21.31 (CDCP1), 10q11.21 (RET) 12p12.3 (PIK3C2G)
      and 16q23.3 (CDH13), respectively. In particular, the CNV region at 10q11.21 was
      examined by  quantitative real-time PCR, the results of which were consistent
      with  microarray findings. CONCLUSIONS: Our preliminary results constitute an
      alternative method of evaluating the relationship between CNV regions and
      cardiovascular disease. These susceptibility CNV regions may be used as
      biomarkers for early-stage diagnosis of hyperlipidemia and myocardial infarction,
      rendering them valuable for further research and discussion.

PMID- 22369087
TI  - Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic
      deletion during eukaryotes evolution.
AB  - BACKGROUND: Besides being building blocks for proteins, amino acids are also key
      metabolic intermediates in living cells. Surprisingly a variety of organisms are
      incapable of synthesizing some of them, thus named Essential Amino Acids (EAAs).
      How certain ancestral organisms successfully competed for survival after losing
      key genes involved in amino acids anabolism remains an open question. Comparative
      genomics searches on current protein databases including sequences from both
      complete and incomplete genomes among diverse taxonomic groups help us to
      understand amino acids auxotrophy distribution. RESULTS: Here, we applied a
      methodology based on clustering of homologous genes to seed sequences from
      autotrophic organisms Saccharomyces cerevisiae (yeast) and Arabidopsis thaliana
      (plant). Thus we depict evidences of presence/absence of EAA biosynthetic and
      nitrogen assimilation enzymes at phyla level. Results show broad loss of the
      phenotype of EAAs biosynthesis in several groups of eukaryotes, followed by
      multiple secondary gene losses. A subsequent inability for nitrogen assimilation
      is observed in derived metazoans. CONCLUSIONS: A Great Deletion model is proposed
      here as a broad phenomenon generating the phenotype of amino acids essentiality
      followed, in metazoans, by organic nitrogen dependency. This phenomenon is
      probably associated to a relaxed selective pressure conferred by heterotrophy
      and, taking advantage of available homologous clustering tools, a complete and
      updated picture of it is provided.

PMID- 22369088
TI  - Understanding the ion jelly conductivity mechanism.
AB  - The properties of the light flexible device, ion jelly, which combines gelatin
      with an ionic liquid (IL) were recently reported being promising to develop safe
      and highly conductive electrolytes. This article aims for the understanding of
      the ion jelly conductive mechanism using dielectric relaxation spectroscopy (DRS)
      in the frequency range 10(-1)-10(6) Hz; the study was complemented with
      differential scanning calorimetry (DSC) and pulsed field gradient nuclear
      magnetic resonance (PFG NMR) spectroscopy. The room temperature ionic liquid 1
      butyl-3-methylimmidazolium dicyanamide (BMIMDCA) used as received (1.9% w/w water
      content) and with 6.6% (w/w) of water content and two ion jellies with two
      different ratios BMIMDCA/gelatin/water % (w/w), IJ1 (41.1/46.7/12.2) and IJ3
      (67.8/25.6/6.6), have been characterized. A glass transition was detected by DSC
      for all materials allowing for classifying them as glass formers. For the ionic
      liquid, it was observed that the glass transition temperature decreases with the
      increase of water content. While in subsequent calorimetric runs crystallization
      was observed for BMIMDCA with negligible water content, no crystallization was
      detected for any of the ion jelly materials upon themal cycling. To the
      dielectric spectra of all tested materials, both dipolar relaxation and
      conductivity contribute; at the lowest frequencies, electrode and interfacial
      polarization highly dominate. Conductivity, which manifests much more intensity
      relative to dipolar reorientations, strongly evidences subdiffusive ion dynamics
      at high frequencies. From dielectric measures, transport properties as mobility
      and diffusion coefficients were extracted. Data treatment was carried out in
      order to deconvolute the average diffusion coefficients estimated from dielectric
      data in its individual contributions of cations (D(+)) and anions (D(-)). The
      D(+) values thus obtained for IJ3, the ion jelly with the highest IL/gelatin
      ratio, cover a large temperature range up to room temperature and revealed
      excellent agreement with direct measurements from PFG NMR, obeying to the same
      VFT equation. For BMIMDCA(6.6%water), which has the same water amount as IJ3, the
      diffusion coefficients were only estimated from DRS measurements over a limited
      temperature range; however, a single VFT equation describes both DRS and PFG NMR
      data. Moreover, it was found that the diffusion coefficients and mobility are
      similar for the ionic liquid and IJ3, which points to a role of both water and
      gelatin weakening the contact ion pair, facilitating the translational motion of
      ions and promoting its dissociation; nevertheless, it is conceivable the
      existence of a critical composition of gelatin that leads to those properties.
      The VFT temperature dependence observed for the conductivity was found to be
      determined by a similar dependence of the mobility. Both conductivity and
      segmental motion revealed to be correlated as inferred by the relatively low
      values of the decoupling indexes. The obtained results show that ion jelly could
      be in fact a very promising material to design novel electrolytes for different
      electrochemical devices, having a performance close to the IL but presenting an
      additional stability regarding electrical measurements and resistance against
      crystallization relative to the bulk ionic liquid.

PMID- 22369089
TI  - Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and
      prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania.
AB  - BACKGROUND: Drug resistance to anti-malarials is a major public health problem
      worldwide. This study aimed at establishing the efficacy of artemether
      lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of
      ACT use, and establish the prevalence of mutations in key targets for
      artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. METHODS: A
      prospective single cohort study was conducted at Igombe health centre using
      artemether-lumefantrine combination therapy between February 2010 and March 2011.
      The follow-up period was 28 days and outcome measures were according to WHO
      guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA
      extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1,
      Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established
      previously. RESULTS: A total of 103 patients completed the 28 days follow-up. The
      mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density
      was 5,608 parasites/MUl. Average parasite clearance time was 34.7 hours and all
      patients cleared the parasites by day 3. There was no early treatment failure in
      this study. Late clinical failure was seen in three (2.9%) patients and late
      parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1%
      and adequate clinical and parasitological response was 96%. The majority of
      parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8%
      and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main
      three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5%
      respectively. Post-treatment parasites had more wild types of pfdhps at position
      437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in
      re-infecting or recrudescing parasites. CONCLUSION: The efficacy of artemether
      lumefantrine for treatment of uncomplicated malaria is still high in the study
      area although the rate of re-infection is higher than previously reported.
      Parasite clearance after 48 hours was lower compared to previous studies. The
      prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study
      area while markers for SP resistance is still high. Artemether-lumefantrine may
      be selecting for wild type alleles on both positions (437 and 540) of pfdhps.

PMID- 22369090
TI  - Quantitation of sensory-active and bioactive constituents of food: A Journal of
      Agricultural and Food Chemistry perspective.
AB  - The proper procedures for the measurement of amounts of compounds that may occur
      in a food or other matrices are presented in this perspective. Factors dealt with
      include sampling, use of standards, advantages and limitations of chromatographic
      and other techniques for quantitation, and proper presentation and reporting of
      data. Such factors must be considered at the initial stages of an investigation
      and incorporated completely into the overall experimental design. These standards
      are to be employed in determining quantities of such components, and their
      careful incorporation should result in more favorable evaluation of manuscripts
      submitted to the Journal of Agricultural and Food Chemistry.

PMID- 22369092
TI  - Detection of orphan receptor tyrosine kinase (ROR-1) expression in Egyptian
      pediatric acute lymphoblastic leukemia.
AB  - Receptor tyrosine kinases, a group of tumor-associated antigens, were introduced
      as targets for cancer intervention strategies. The human orphan receptor tyrosine
      kinase-1 (ROR-1) is a member of this family. Overexpression of ROR1 has been
      reported in B-cell chronic lymphocytic leukemia. The aim of this study was to
      detect the expression profile of ROR1 in 54 pediatric acute lymphoblastic
      leukemia (ALL) patients. ROR1 was overexpressed in ALL as the ROR1/ beta-actin
      ratio was higher in ALL children than in control group (P = 0.024). ROR1 is a
      potential tool for targeted immunotherapy in pediatric ALL patients.

PMID- 22369093
TI  - Production of H2O2 in the endoplasmic reticulum promotes in vivo disulfide bond
      formation.
AB  - AIMS: Oxidative protein folding in the luminal compartment of endoplasmic
      reticulum (ER) is thought to be accompanied by the generation of H2O2, as side
      product of disulfide bond formation. We aimed to examine the role of H2O2
      produced in the lumen, which on one hand can lead to redox imbalance and hence
      can contribute to ER stress caused by overproduction of secretory proteins; on
      the other hand, as an excellent electron acceptor, H2O2 might serve as an
      additional pro-oxidant in physiological oxidative folding. RESULTS: Stimulation
      of H2O2 production in the hepatic ER resulted in a decrease in microsomal GSH and
      protein-thiol contents and in a redox shift of certain luminal oxidoreductases in
      mice. The oxidative effect, accompanied by moderate signs of ER stress and
      reversible dilation of ER cisternae, was prevented by concomitant reducing
      treatment. The imbalance also affected the redox state of pyridine nucleotides in
      the ER. Antibody producing cells artificially engineered with powerful luminal
      H2O2 eliminating system showed diminished secretion of mature antibody polymers,
      while incomplete antibody monomers/dimers were accumulated and/or secreted.
      INNOVATION: Evidence are provided by using in vivo models that hydrogen peroxide
      can promote disulfide bond formation in the ER. CONCLUSION: The results indicate
      that local H2O2 production promotes, while quenching of H2O2 impairs disulfide
      formation. The contribution of H2O2 to disulfide bond formation previously
      observed in vitro can be also shown in cellular and in vivo systems.

PMID- 22369091
TI  - Hsp90 is important for fecundity, longevity, and buffering of cryptic deleterious
      variation in wild fly populations.
AB  - BACKGROUND: In the laboratory, the Drosophila melanogaster heat shock protein
      Hsp90 can buffer the phenotypic effects of genetic variation. Laboratory
      experiments either manipulate Hsp90 activity pharmacologically, or they induce
      mutations with strong effects in the gene Hsp83, the single-copy fly gene
      encoding Hsp90. It is unknown whether observations from such laboratory
      experiments are relevant in the wild. RESULTS: We here study naturally occurring
      mutations in Hsp83, and their effects on fitness and phenotypic buffering in
      flies derived from wild populations. We examined more than 4500 flies from 42
      Drosophila populations distributed world-wide for insertions or deletions of
      mobile DNA in or near the Hsp83 gene. The insertions we observed occur at low
      population frequencies, and reduce Hsp83 gene expression. In competition
      experiments, mutant flies performed much more poorly than wild-type flies. Mutant
      flies were also significantly less fecund and shorter-lived than wild-type flies,
      as well as less well buffered against cryptic deleterious variation, as we show
      through inbreeding experiments. Specifically, in Hsp83 mutant flies female
      fecundity dropped to much lower levels after inbreeding than in wild-type flies.
      At even slightly elevated temperatures, inbred mutant Hsp83 populations went
      extinct, whereas inbred wild-type populations persisted. CONCLUSIONS: Our work
      shows that Hsp90, a regulator of the stress response and of signaling, helps
      buffer deleterious variation in fruit flies derived from wild population, and
      that its buffering role becomes even more important under heat stress.

PMID- 22369094
TI  - Direct observation of tetrahedrally coordinated Fe(III) in ferrihydrite.
AB  - Ferrihydrite is a common iron hydroxide nanomineral commonly found in soils,
      sediments, and surface waters. Reactivity with this important environmental
      surface often controls the fate and mobility of both essential nutrients and
      inorganic contaminants. Despite the critical role of ferrihydrite in
      environmental geochemistry, its structure is still debated. In this work, we
      apply bulk sensitive Fe L edge X-ray absorption spectroscopy to study the crystal
      field environment of the Fe in ferrihydrite and other Fe oxides of known
      structure. This direct probe of the local electronic structure provides
      verification of the presence of tetrahedrally coordinated Fe(III) in the
      structure of ferrihydrite and puts to rest the controversy on this issue.

PMID- 22369096
TI  - Expression of dopamine receptors in human lower esophageal sphincter.
AB  - BACKGROUND AND AIM: Dopamine (DA) is considered to be an important modulator of
      enteric function. Recent experiments have suggested that DA receptors are widely
      expressed in animal gastrointestinal tract. The aim of this study was to explore
      the expression of DA receptors (D(1) R, D(2) R, D(3) R, D(4) R, D(5) R) in sling
      fibers and clasp fibers from the human lower esophageal sphincter (LES). METHODS:
      Muscle strips of sling and clasp fibers from the LES were obtained from patients
      undergoing esophago-gastrectomy, and circular muscle strips from the esophagus
      and stomach were used as controls. Reverse transcription-polymerase chain
      reaction and western blotting were used to determine the expression of the five
      subtypes of DA receptors. RESULTS: Messenger RNA and protein for three of five DA
      receptors were identified in the sling and clasp fibers of the LES. Expression
      was highest for D(1) R, then D(5) R and D(2) R in decreasing levels. D(3) R and
      D(4) R mRNA and protein were not identified in the muscle strips. CONCLUSION:
      D(1) R, D(2) R, D(5) R can be detected in the human LES, and probably contribute
      to LES function. D(3) R and D(4) R are not expressed, and probably do not
      contribute to LES function in humans.

PMID- 22369095
TI  - Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not
      buprenorphine maintenance patients.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Management of pain in opioid dependent
      individuals is problematic due to numerous issues including cross-tolerance to
      opioids. Hence there is a need to find alternative analgesics to classical
      opioids and tramadol is potentially one such alternative. Methadone inhibits
      CYP2D6 in vivo and in vitro. We aimed to investigate the effect of methadone on
      the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid
      active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on
      methadone or buprenorphine as a control. WHAT THIS STUDY ADDS: Compared with
      subjects on buprenorphine, methadone reduced the clearance of tramadol to active
      O-desmethyl-tramadol (M1) but had no effect on N-desmethyltramadol (M2)
      formation. Similar to other analgesics whose active metabolites are formed by
      CYP2D6 such as codeine, reduced formation of O-desmethyltramadol (M1) is likely
      to result in reduced analgesia for subjects maintained on methadone. Hence
      alternative analgesics whose metabolism is independent of CYP2D6 should be
      utilized in this patient population. AIMS: To compare the O- (CYP2D6 mediated)
      and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone
      and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine
      methadone and seven buprenorphine maintained subjects received a single 100 mg
      dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for
      tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and
      all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites.
      RESULTS: The urinary metabolic ratio [median (range)] for O-demethylation (M1)
      was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking
      methadone [0.071 (0.012-0.103)] compared with those taking buprenorphine [0.192
      (0.108-0.392)], but there was no significant difference (P= 0.21, probability
      score 0.69) in N-demethylation (M2). The percentage of dose [median (range)]
      recovered as M1 was significantly lower in subjects taking methadone compared
      with buprenorphine (0.069 (0.044-0.093) and 0.126 (0.069-0.187), respectively, P=
      0.04, probability score 0.19), M2 was significantly higher in subjects taking
      methadone compared with buprenorphine (0.048 (0.033-0.085) and 0.033 (0.014
      0.049), respectively, P= 0.04, probability score 0.81). Tramadol was similar
      (0.901 (0.635-1.30) and 0.685 (0.347-1.04), respectively, P= 0.35, probability
      score 0.65). CONCLUSIONS: Methadone inhibited the CYP2D6-mediated metabolism of
      tramadol to M1. Hence, as the degree of opioid analgesia is largely dependent on
      M1 formation, methadone maintenance patients may not receive adequate analgesia
      from oral tramadol.

PMID- 22369097
TI  - Iron(III)/NaBH4-mediated additions to unactivated alkenes: synthesis of novel 20'
      vinblastine analogues.
AB  - An Fe(III)/NaBH(4)-mediated reaction for the functionalization of unactivated
      alkenes is described defining the alkene substrate scope, establishing the
      exclusive Markovnikov addition, exploring a range of free radical traps,
      examining the Fe(III) salt and initiating hydride source, introducing H(2)O
      cosolvent mixtures, and exploring catalytic variants. Its use led to the
      preparation of a novel, potent, and previously inaccessible C20'-vinblastine
      analogue.

PMID- 22369098
TI  - Direct measurements of pore fluid density by vibrating tube densimetry.
AB  - The densities of pore-confined fluids were measured for the first time by means
      of vibrating tube densimetry (VTD). A custom-built high-pressure, high
      temperature vibrating tube densimeter was used to measure the densities of
      propane at subcritical and supercritical temperatures (between 35 and 97  degrees
      C) and carbon dioxide at supercritical temperatures (between 32 and 50  degrees
      C) saturating hydrophobic silica aerogel (0.2 g/cm(3), 90% porosity) synthesized
      inside Hastelloy U-tubes. Additionally, supercritical isotherms of excess
      adsorption for CO(2) and the same porous solid were measured gravimetrically
      using a precise magnetically coupled microbalance. Pore fluid densities and total
      adsorption isotherms increased monotonically with increasing density of the bulk
      fluid, in contrast to excess adsorption isotherms, which reached a maximum and
      then decreased toward zero or negative values above the critical density of the
      bulk fluid. The isotherms of confined fluid density and excess adsorption
      obtained by VTD contain additional information. For instance, the maxima of
      excess adsorption occur below the critical density of the bulk fluid at the
      beginning of the plateau region in the total adsorption, marking the end of the
      transition of pore fluid to a denser, liquidlike pore phase. Compression of the
      confined fluid significantly beyond the density of the bulk fluid at the same
      temperature was observed even at subcritical temperatures. The effect of pore
      confinement on the liquid-vapor critical temperature of propane was less than
      ~1.7 K. The results for propane and carbon dioxide showed similarity in the sense
      of the principle of corresponding states. Good quantitative agreement was
      obtained between excess adsorption isotherms determined from VTD total adsorption
      results and those measured gravimetrically at the same temperature, confirming
      the validity of the vibrating tube measurements. Thus, it is demonstrated that
      vibrating tube densimetry is a novel experimental approach capable of providing
      directly the average density of pore-confined fluids, and hence complementary to
      the conventional gravimetric or volumetric/piezometric adsorption techniques,
      which yield the excess adsorption (the Gibbsian surface excess).

PMID- 22369099
TI  - A robust tool for discriminative analysis and feature selection in paired samples
      impacts the identification of the genes essential for reprogramming lung tissue
      to adenocarcinoma.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer deaths in the world. The
      most common type of lung cancer is lung adenocarcinoma (AC). The genetic
      mechanisms of the early stages and lung AC progression steps are poorly
      understood. There is currently no clinically applicable gene test for the early
      diagnosis and AC aggressiveness. Among the major reasons for the lack of reliable
      diagnostic biomarkers are the extraordinary heterogeneity of the cancer cells,
      complex and poorly understudied interactions of the AC cells with adjacent tissue
      and immune system, gene variation across patient cohorts, measurement
      variability, small sample sizes and sub-optimal analytical methods. We suggest
      that gene expression profiling of the primary tumours and adjacent tissues (PT
      AT) handled with a rational statistical and bioinformatics strategy of biomarker
      prediction and validation could provide significant progress in the
      identification of clinical biomarkers of AC. To minimise sample-to-sample
      variability, repeated multivariate measurements in the same object (organ or
      tissue, e.g. PT-AT in lung) across patients should be designed, but prediction
      and validation on the genome scale with small sample size is a great methodical
      challenge. RESULTS: To analyse PT-AT relationships efficiently in the statistical
      modelling, we propose an Extreme Class Discrimination (ECD) feature selection
      method that identifies a sub-set of the most discriminative variables (e.g.
      expressed genes). Our method consists of a paired Cross-normalization (CN) step
      followed by a modified sign Wilcoxon test with multivariate adjustment carried
      out for each variable. Using an Affymetrix U133A microarray paired dataset of 27
      AC patients, we reviewed the global reprogramming of the transcriptome in human
      lung AC tissue versus normal lung tissue, which is associated with about 2,300
      genes discriminating the tissues with 100% accuracy. Cluster analysis applied to
      these genes resulted in four distinct gene groups which we classified as
      associated with (i) up-regulated genes in the mitotic cell cycle lung AC, (ii)
      silenced/suppressed gene specific for normal lung tissue, (iii) cell
      communication and cell motility and (iv) the immune system features. The genes
      related to mutagenesis, specific lung cancers, early stage of AC development,
      tumour aggressiveness and metabolic pathway alterations and adaptations of cancer
      cells are strongly enriched in the AC PT-AT discriminative gene set. Two AC
      diagnostic biomarkers SPP1 and CENPA were successfully validated on RT-RCR tissue
      array. ECD method was systematically compared to several alternative methods and
      proved to be of better performance and as well as it was validated by comparison
      of the predicted gene set with literature meta-signature. CONCLUSIONS: We
      developed a method that identifies and selects highly discriminative variables
      from high dimensional data spaces of potential biomarkers based on a statistical
      analysis of paired samples when the number of samples is small. This method
      provides superior selection in comparison to conventional methods and can be
      widely used in different applications. Our method revealed at least 23 hundreds
      patho-biologically essential genes associated with the global transcriptional
      reprogramming of human lung epithelium cells and lung AC aggressiveness. This
      gene set includes many previously published AC biomarkers reflecting inherent
      disease complexity and specifies the mechanisms of carcinogenesis in the lung AC.
      SPP1, CENPA and many other PT-AT discriminative genes could be considered as the
      prospective diagnostic and prognostic biomarkers of lung AC.

PMID- 22369101
TI  - A modular hierarchy-based theory of the chemical origins of life based on
      molecular complementarity.
AB  - Albert Szent-Gyorgyi once defined discovery as seeing what everyone else sees and
      thinking what no one else thinks. I often find that phenomena that are obvious to
      other people are not obvious to me. Molecular complementarity is one of these
      phenomena: while rare among any random set of compounds, it is ubiquitous in
      living systems. Because every molecule in a living system binds more or less
      specifically to several others, we now speak of "interactomes". What explains the
      ubiquity of molecular complementarity in living systems? What might such an
      explanation reveal about the chemical origins of life and the principles that
      have governed its evolution? Beyond this, what might complementarity tell us
      about the optimization of integrated systems in general?  My research combines
      theoretical and experimental approaches to molecular complementarity relating to
      evolution from prebiotic chemical systems to superorganismal interactions.
      Experimentally, I have characterized complementarity involving specific binding
      between small molecules and explored how these small-molecule modules have been
      incorporated into macromolecular systems such as receptors and transporters.
      Several general principles have emerged from this research. Molecules that bind
      to each other almost always alter each other's physiological effects; and
      conversely, molecules that have antagonistic or synergistic physiological effects
      almost always bind to each other. This principle suggests a chemical link between
      biological structure and function. Secondly, modern biological systems contain an
      embedded molecular paleontology based on complementarity that can reveal their
      chemical origins. This molecular paleontology is often manifested through modules
      involving small, molecularly complementary subunits that are built into modern
      macromolecular structures such as receptors and transporters. A third principle
      is that complementary modules are conserved and repurposed at every stage of
      evolution.  Molecular complementarity plays critical roles in the evolution of
      chemical systems and resolves a significant number of outstanding problems in the
      emergence of complex systems. All physical and mathematical models of
      organization within complex systems rely upon nonrandom linkage between
      components. Molecular complementarity provides a naturally occurring nonrandom
      linker. More importantly, the formation of hierarchically organized stable
      modules vastly improves the probability of achieving self-organization, and
      molecular complementarity provides a mechanism by which hierarchically organized
      stable modules can form. Finally, modularity based on molecular complementarity
      produces a means for storing and replicating information. Linear replicating
      molecules such as DNA or RNA are not required to transmit information from one
      generation of compounds to the next: compositional replication is as ubiquitous
      in living systems as genetic replication and is equally important to its
      functions. Chemical systems composed of complementary modules mediate this
      compositional replication and gave rise to linear replication schemes.  In sum, I
      propose that molecular complementarity is ubiquitous in living systems because it
      provides the physicochemical basis for modular, hierarchical ordering and
      replication necessary for the evolution of the chemical systems upon which life
      is based. I conjecture that complementarity more generally is an essential agent
      that mediates evolution at every level of organization.

PMID- 22369100
TI  - Analysis of the transcriptome of Panax notoginseng root uncovers putative
      triterpene saponin-biosynthetic genes and genetic markers.
AB  - BACKGROUND: Panax notoginseng (Burk) F.H. Chen is important medicinal plant of
      the Araliacease family. Triterpene saponins are the bioactive constituents in P.
      notoginseng. However, available genomic information regarding this plant is
      limited. Moreover, details of triterpene saponin biosynthesis in the Panax
      species are largely unknown. RESULTS: Using the 454 pyrosequencing technology, a
      one-quarter GS FLX titanium run resulted in 188,185 reads with an average length
      of 410 bases for P. notoginseng root. These reads were processed and assembled by
      454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2%
      of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST)
      similarity searches against public sequence databases. The Kyoto Encyclopedia of
      Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing
      11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST
      dataset. In particular, the transcript encoding dammarenediol synthase (DS),
      which is the first committed enzyme in the biosynthetic pathway of major
      triterpene saponins, is highly expressed in the root of four-year-old P.
      notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132
      and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be
      involved in hydroxylation or glycosylation of aglycones for triterpene saponin
      biosynthesis were discovered from 174 cytochrome P450s and 242
      glycosyltransferases by phylogenetic analysis, respectively. Putative
      transcription factors were detected in 906 unique sequences, including Myb,
      homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins.
      Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from
      2,361 unique sequences, of which, di-nucleotide motifs were the most abundant
      motif. CONCLUSION: This study is the first to present a large-scale EST dataset
      for P. notoginseng root acquired by next-generation sequencing (NGS) technology.
      The candidate genes involved in triterpene saponin biosynthesis, including the
      putative CYP450s and UGTs, were obtained in this study. Additionally, the
      identification of SSRs provided plenty of genetic makers for molecular breeding
      and genetics applications in this species. These data will provide information on
      gene discovery, transcriptional regulation and marker-assisted selection for P.
      notoginseng. The dataset establishes an important foundation for the study with
      the purpose of ensuring adequate drug resources for this species.

PMID- 22369104
TI  - The effect of glycerol concentrations on the post-thaw in vitro characteristics
      of cryopreserved sex-sorted boar spermatozoa.
AB  - The objective of this study was to optimize protocols for the cryopreservation of
      sex-sorted boar spermatozoa. In the experiment 1, we evaluated the effects of a
      standard boar sperm cryopreservation procedure (3% final glycerol concentration)
      on the in vitro characteristics of sex-sorted sperm frozen at low sperm
      concentrations (20 * 10(6) sperm/ml; S20 group). Non-sorted spermatozoa frozen at
      1000 * 10(6) (C1000 group) and 20 * 10(6) (C20 group) sperm/ml were used as the
      freezing control groups. In experiment 2, the effects of different final glycerol
      concentrations (0.16%, 0.5%, 1.0%, 2.0% and 3.0%) on post-thaw quality of the S20
      and C20 groups were evaluated. In both experiments, the samples were evaluated
      prior to freezing (5 degrees C) and at 30, 90 and 150 min after thawing.
      Experiment 1 indicated that freezing sperm at low concentrations decreased (p <
      0.05) the total motility (TM) and progressive motility (PM) at 90 and 150 min
      after thawing regardless of whether the sperm were sorted or not. However, the
      sperm membrane integrity was not affected at any evaluation step. Inexperiment 2,
      significant effects on the TM and PM because of increased glycerol concentrations
      in the S20 and C20 groups were observed only at 90 and 150 min after thawing. The
      samples frozen in 3% glycerol showed lower (p < 0.05) TM and PM values when
      compared to those frozen in the presence of 0.5% and 1% glycerol. In both
      experiments, non-sorted control samples displayed higher percentages of
      spermatozoa with damaged DNA than sorted spermatozoa. In conclusion, the
      optimization of cryopreservation conditions by decreasing the glycerol
      concentrations can improve post-thaw motility of sex-sorted spermatozoa frozen at
      low concentrations.

PMID- 22369103
TI  - Preimplantation development regulatory pathway construction through a text-mining
      approach.
AB  - BACKGROUND: The integration of sequencing and gene interaction data and
      subsequent generation of pathways and networks contained in databases such as
      KEGG Pathway is essential for the comprehension of complex biological processes.
      We noticed the absence of a chart or pathway describing the well-studied
      preimplantation development stages; furthermore, not all genes involved in the
      process have entries in KEGG Orthology, important information for knowledge
      application with relation to other organisms. RESULTS: In this work we sought to
      develop the regulatory pathway for the preimplantation development stage using
      text-mining tools such as Medline Ranker and PESCADOR to reveal biointeractions
      among the genes involved in this process. The genes present in the resulting
      pathway were also used as seeds for software developed by our group called
      SeedServer to create clusters of homologous genes. These homologues allowed the
      determination of the last common ancestor for each gene and revealed that the
      preimplantation development pathway consists of a conserved ancient core of genes
      with the addition of modern elements. CONCLUSIONS: The generation of regulatory
      pathways through text-mining tools allows the integration of data generated by
      several studies for a more complete visualization of complex biological
      processes. Using the genes in this pathway as "seeds" for the generation of
      clusters of homologues, the pathway can be visualized for other organisms. The
      clustering of homologous genes together with determination of the ancestry leads
      to a better understanding of the evolution of such process.

PMID- 22369105
TI  - Effects of methylphenidate on attentional set-shifting in a genetic model of
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Although deficits of attentional set-shifting have been reported in
      individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely
      examined in animal models. METHODS: This study compared spontaneously
      hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY)
      and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set
      shifting task (ASST) performance. Furthermore, the dose-effects of
      methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In
      experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at
      the age of 5 weeks. Mean latencies at the initial phase, error types and numbers,
      and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats
      were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher
      dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or
      5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested
      in the ASST at the age of 5 weeks. RESULTS: The SHRs generally exhibited poorer
      performance on ASST than the control WKY and SD rats. Significant strain effects
      on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2,
      21) = 114.118, p < 0.001] were observed. The SHRs were found to have more
      perseverative and regressive errors than the control strains (p < 0.001). After
      MPH treatment, the two MPH treated groups exhibited significantly longer latency
      and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L
      group exhibited fewer trials to reach criterion in more stages compared with the
      MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p <
      0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. CONCLUSIONS:
      The SHR may be impaired in discrimination learning, reversal learning and
      attentional set-shifting. Our study provides evidence that MPH may improve the
      SHR's performance on attentional set-shifting and lower dose is more effective
      than higher dose.

PMID- 22369106
TI  - A 39 year-old man with a cerebellar mass and pancytopenia.

PMID- 22369102
TI  - Metformin monotherapy in youth with recent onset type 2 diabetes: experience from
      the prerandomization run-in phase of the TODAY study.
AB  - BACKGROUND: TODAY (Treatment Options for type 2 Diabetes in Adolescents and
      Youth) is a federally funded multicenter randomized clinical trial comparing
      three treatments of youth onset type 2 diabetes. OBJECTIVE: To describe the
      experience of youth participating in a 2-6 month run-in period in preparation for
      randomization into TODAY. SUBJECTS: An ethnically diverse sample of 927 youth,
      65.4% females, aged 13.7 +/- 2.0 yr old, with type 2 diabetes for a median of 2
      months (0.7-7.8 months, 25th-75th percentiles). METHODS: A run-in period was
      conducted to achieve HbA1c <8% with metformin monotherapy and diabetes education,
      and to evaluate adherence to pill taking, visit attendance, and other procedures.
      RESULTS: At entry, mean body mass index (BMI) and z-BMI were 35.6 +/- 7.7 and 2.3
      +/- 0.4, respectively, mean HbA1c was 7.7 +/- 2.2%, only 42.5% were on a
      hypoglycemic treatment, and 35.6% had HbA1c >=8%. Comorbid conditions were
      common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had
      abnormal liver enzymes. After a median 71 d of run-in, 90.9% had HbA1c <8%, 77.9%
      had HbA1c <7%, and 46.4% had HbA1c <6%. Of the 772 youth achieving the target
      HbA1c <8%, 704 (91.2%) were randomized; non-adherence to metformin treatment was
      the main cause for non-randomization. Youth proceeding to randomization decreased
      weight by 0.68 kg and HbA1c by 1.45% compared to a weight gain of 0.71 kg and
      HbA1c decrease of 0.74% in the non-randomized youth (p = 0.01 in both cases).
      However, change in z-BMI was not significantly different between the two groups.
      CONCLUSIONS: Most youth with recent onset type 2 diabetes can achieve target
      HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education
      (ClinicalTrials.gov identifier: NCT00081328).

PMID- 22369107
TI  - 45 year old man with a pineal region tumor for over 15 years.

PMID- 22369108
TI  - Advocacy for neuropathology in practice: ISN information days.

PMID- 22369109
TI  - Teaching the Y generation obstetrics and gynaecology skills: a survey of medical
      students' thoughts on a new program.
AB  - BACKGROUND: Delivering undergraduate obstetrics and gynaecology teaching to
      classes of increasing size in ways which will foster student interest in the
      discipline is becoming increasingly challenging. With major curriculum change
      implemented at Otago Medical School in 2008, we had the opportunity to rise to
      this challenge. AIM: To assess an innovative obstetrics and gynaecology history
      taking and examination skills unit, introduced to third-year medical students.
      METHOD: A survey of medical students and pregnant women who participated in the
      unit. RESULTS: There was a 92% response rate from students and a 73% response
      from the pregnant women who took part. Overall feedback was positive from both
      groups, with the unit being highly rated across a number of parameters.
      CONCLUSION: Despite increasing limitations on staffing, obstetric clinical skills
      can be taught to large class sizes with close contact between students and
      specialists, safely incorporating the use of 'real patients'. Students are very
      positive about this exposure to O&G, and we hope that this may result in
      increased student confidence and interest in O&G, with a subsequent improvement
      in recruitment.

PMID- 22369110
TI  - Rapid downregulation of cyclin D1 induced by geranylgeranoic acid in human
      hepatoma cells.
AB  - Geranylgeranoic acid (GGA) and its derivatives are currently under development as
      chemopreventive agents against second primary hepatoma in Japan. We aimed to
      evaluate chemoprevention targets of GGA and a surrogate marker of chemopreventive
      response to clarify the molecular mechanism of hepatoma chemoprevention with GGA.
      Human hepatoma-derived cell lines such as HuH-7, PLC/PRF/5, and HepG-2, were
      treated with GGA and its derivatives. Cellular dynamics of several cell-cycle
      related proteins were assessed by either immunoblotting or immunofluorescence
      method. The cellular expression of cyclin D1 protein was suppressed immediately
      after GGA treatment. This reduction was partially blocked by pretreatment with
      26S proteasome inhibitor MG-132, indicating that proteasomal degradation was
      involved in GGA-induced disappearance of cyclin D1. A phosphorylation of
      retinoblastoma protein (RB) at serine 780, a target site of cyclin D1-dependent
      kinase 4, was rapidly decreased in GGA-treated HuH-7 cells. Furthermore,
      subcellular fractionation, Western blotting, and immunofluorescence revealed GGA
      induced nuclear accumulation of RB. These results strongly suggest that cyclin D1
      may be a target of chemopreventive GGA in human hepatoma cells. GGA-induced rapid
      repression of cyclin D1, and a consequent dephosphorylation and nuclear
      translocation of RB, may influence cell cycle progression and may be relevant to
      GGA-induced cell death mechanisms.

PMID- 22369111
TI  - Adaptative capacity of mitochondrial biogenesis and of mitochondrial dynamics in
      response to pathogenic respiratory chain dysfunction.
AB  - AIMS: Cellular energy homeostasy relies on mitochondrial plasticity, the
      molecular determinants of which are multiple. Yet, the relative contribution of
      and possible cooperation between mitochondrial biogenesis and morphogenesis to
      cellular energy homeostasy remains elusive. Here we analyzed the adaptative
      capacity of mitochondrial content and dynamics in muscle biopsies of patients
      with a complex IV defect, and in skin fibroblasts challenged with complex IV
      inhibition. RESULTS: We observed a biphasic variation of the mitochondrial
      content upon complex IV inhibition in muscle biopsies and in skin fibroblasts.
      Adjustment of mitochondrial content for respiratory maintenance was blocked by
      using a dominant negative form of CREB (CREB-M1) and by L-NAME, a blocker of NO
      production. Accordingly, cells treated with KCN 6 MUM showed higher levels of
      phospho-CREB, PGC1alpha mRNA, eNOS mRNA, and mtTFA mRNA. We also observed the
      increased expression of the fission protein DRP1 during fibroblasts adaptation,
      as well as mitochondrial ultrastructural defects indicative of increased fission
      in patients muscle micrographs. Accordingly, the expression of a dominant
      negative form of DRP1 (K38A mutant) reduced the biogenic response in fibroblasts
      challenged with 6 MUM KCN. INNOVATION: Our findings indicate that mitochondrial
      biogenesis and mitochondrial fission cooperate to promote cellular adaptation to
      respiratory chain inhibition. CONCLUSIONS: Our data show for the first time that
      DRP1 intervenes during the initiation of the mitochondrial adaptative response to
      respiratory chain defects. The evidenced pathway of mitochondrial adaptation to
      respiratory chain deficiency provides a safety mechanism against mitochondrial
      dysfunction.

PMID- 22369112
TI  - Opening commentary: Rehabilitation Psychology, 2012-2017.
AB  - On behalf of the new editorial team, let me welcome you to this first issue of
      Rehabilitation Psychology under our leadership. We are excited and honored by
      this responsibility. We look forward to serving the readership, authors, and the
      entire rehabilitation community as we develop and grow the flagship journal of
      rehabilitation psychology. As part of the editorial transition, I want to take
      this opportunity to reflect on our history, define our mission, encourage our
      team, and explore our future. (PsycINFO Database Record (c) 2012 APA, all rights
      reserved).

PMID- 22369113
TI  - Financial capacity following traumatic brain injury: a six-month longitudinal
      study.
AB  - OBJECTIVE: To longitudinally investigate financial capacity (FC) following
      traumatic brain injury (TBI). DESIGN: Longitudinal study comparing FC in
      cognitively healthy adults and persons with moderate to severe TBI at time of
      acute hospitalization (Time 1) and at 6 months postinjury (Time 2). SETTING:
      Inpatient brain injury rehabilitation unit. PARTICIPANTS: Twenty healthy adult
      controls and 24 adult persons with moderate to severe TBI. MAIN OUTCOME MEASURES:
      Participants were administered the Financial Capacity Instrument (FCI-9), a
      standardized instrument that measures performance on 18 financial tasks, 9
      domains, and 2 global scores. Between- and within-group differences were examined
      for each FCI-9 domain and global scores. Using control group referenced cut
      scores, participants with TBI were also assigned an impairment rating (intact,
      marginal, or impaired) on each domain and global score. RESULTS: At Time 1,
      participants with TBI performed significantly below controls on the majority of
      financial variables tested. At Time 2, participants with TBI demonstrated within
      group improvement on both simple and complex financial domains, but continued to
      perform below adult controls on complex financial domains and both global scores.
      Group by time interactions were significant for four domains and both global
      scores. At Time 1, high percentages of participants with TBI were assigned either
      "marginal" or "impaired" ratings on the domains and global scores, with
      significant percentage increases of "intact" ratings at Time 2. CONCLUSIONS:
      Immediately following acute injury, persons with moderate to severe TBI show
      global impairment of FC. Findings indicate improvement of both simple and complex
      financial skills over a 6-month period, but continued impairment on more complex
      financial skills. Future studies should examine loss and recovery of FC following
      TBI over longer time periods and a wider range of injury severity.

PMID- 22369114
TI  - Does a history of mild traumatic brain injury increase suicide risk in veterans
      with PTSD?
AB  - OBJECTIVE: Research shows that posttraumatic stress disorder (PTSD) and mild
      traumatic brain injury (mTBI) independently increase suicide risk; however, scant
      research has investigated whether mTBI increases suicide risk above and beyond
      the risk associated with PTSD alone. DESIGN: The current research compared
      suicide risk factors among a matched sample of Operation Enduring Freedom and
      Operation Iraqi Freedom (OEF/OIF) military personnel and veterans with PTSD alone
      or PTSD and a history of an mTBI. RESULTS: Differences in the assessed risk
      factors were small and suggest that if PTSD and mTBI are associated with
      elevations in suicide risk relative to PTSD alone, the added risk is likely
      mediated or confounded by PTSD symptom severity. CONCLUSION: This finding
      highlights the importance of screening and treating military personnel and
      veterans for PTSD. Future explication of the impact of TBI-related impairments on
      suicide risk will be critical as we strive to ensure safety and optimize care for
      our military personnel and veterans.

PMID- 22369115
TI  - Possible antecedents and consequences of self-esteem in persons with multiple
      sclerosis: preliminary evidence from a cross-sectional analysis.
AB  - BACKGROUND: Persons with multiple sclerosis (MS) have consistently reported lower
      levels of self-esteem compared with the general population. Despite this, very
      little is known about the antecedents and consequences of self-esteem in persons
      with MS. OBJECTIVES: To examine (1) physical activity and social support as
      potentially modifiable correlates (i.e., antecedents) of self-esteem and (2)
      physical and psychological health-related quality of life as possible
      consequences of self-esteem in persons with MS. METHODS: Participants (N = 46)
      wore an Actigraph accelerometer for 7 days and then completed a battery of
      questionnaires, including the Rosenberg Self-Esteem Scale (RSES), Multiple
      Sclerosis Impact Scale (MSIS-29), and Social Provisions Scale (SPS). The data
      were analyzed using PASW Statistics 18. RESULTS: Bivariate correlation analysis
      indicated that average daily step counts (r = .298, p = .026) and social support
      (r = .366, p = .007) were significantly correlated with self-esteem. Multiple
      linear regression analysis indicated that only social support was a significant
      predictor of self-esteem scores (beta = .411, p = .004); pedometer steps
      approached significance as a predictor of self-esteem (beta = .178, p = .112).
      Bivariate correlation analysis further indicated significant negative
      associations between self-esteem and physical (r = -.391, p = .004) and
      psychological (r = -.540, p = .0001) domains of health-related quality of life
      (HRQOL), indicating that higher self-esteem was associated with more positive
      HRQOL. CONCLUSIONS: Social support is a potentially modifiable variable that may
      be important to target when designing interventions to improve self-esteem and
      this might have implications for improving physical and psychological HRQOL in
      persons with MS.

PMID- 22369117
TI  - Parenting difficulties and resources: the perspectives of parents with multiple
      sclerosis and their partners.
AB  - OBJECTIVE: The needs of parents affected by multiple sclerosis (MS) have been
      neglected. Data are required to inform the development of evidenced-based
      clinical practice, services, and policies that will maximize the parenting
      capacities of parents with MS and their partners, while at the same time protect
      the welfare of children. The purpose of this exploratory study was to provide
      descriptive data on the difficulties and resources associated with parenting with
      MS. METHOD: Qualitative data on parenting difficulties and resources were
      obtained from parents with MS and their partners in the form of written responses
      to 2 open-ended questions in a questionnaire survey. A total of 145 parents with
      MS and 91 partners were recruited through MS societies in Australia; 119 parents
      with MS and 64 partners provided qualitative data. The data were analyzed using
      the Leximancer text analysis software. RESULTS: Ten difficulty themes emerged
      (ordered from the most to the least strong): activities, time, MS, fatigue, sons,
      partner, daughters, housework, family, and mood. Some of these difficulties were
      more closely affiliated with 1 parent, whereas others were shared, affecting both
      parents. Eight resource themes emerged: school, time, assistance, chores, friends
      and family, spouse, sons, and driving. Parents with MS and partners accessed
      common and unique resources. CONCLUSIONS: The complex array of interacting
      parenting difficulties was mirrored by a similarly multifaceted assortment of
      resources required to address the parenting difficulties. Findings delineate key
      interrelated parenting needs that can be targeted by services and policy
      development.

PMID- 22369116
TI  - Compensatory expressive behavior for facial paralysis: adaptation to congenital
      or acquired disability.
AB  - OBJECTIVE: Although there has been little research on the adaptive behavior of
      people with congenital compared to acquired disability, there is reason to
      predict that people with congenital conditions may be better adapted because they
      have lived with their conditions for their entire lives (Smart, 2008). We
      examined whether people with congenital facial paralysis (FP), compared to people
      with acquired FP, compensate more for impoverished facial expression by using
      alternative channels of expression (i.e., voice and body). RESEARCH
      METHOD/DESIGN: Participants with congenital (n = 13) and acquired (n = 14) FP
      were videotaped while recalling emotional events. MAIN OUTCOME MEASURES:
      Expressive verbal behavior was measured using the Linguistic Inquiry Word Count
      (Pennebaker, Booth, & Francis, 2007). Nonverbal behavior and FP severity were
      rated by trained coders. RESULTS: People with congenital FP, compared to acquired
      FP, used more compensatory expressive verbal and nonverbal behavior in their
      language, voices, and bodies. The extent of FP severity had little effect on
      compensatory expressivity. CONCLUSIONS/IMPLICATIONS: This study provides the
      first behavioral evidence that people with congenital FP use more adaptations to
      express themselves than people with acquired FP. These behaviors could inform
      social functioning interventions for people with FP.

PMID- 22369118
TI  - Evaluating a dynamic process model of wellbeing for parents of children with
      disabilities: a multi-method analysis.
AB  - PURPOSE: The purpose of this study was to evaluate possible determinants of
      parent wellbeing using a contextual model of parent adjustment. METHOD: One
      hundred forty parents of children with various disabilities (i.e., autism,
      intellectual disabilities, and other health impairments) participated in this
      investigation. Parents completed a survey consisting of basic demographic
      characteristics of the parent, child-disability characteristics, parent problem
      solving ability, access to information and resources, environmental/social
      supports, appraisals of threat and growth, and measures of life satisfaction and
      physical/mental health. Structural equation modeling was conducted to test a
      hypothesized contextual model of parent wellbeing. RESULTS: Results indicated
      strong fit to the a priori model. After controlling for the contribution of
      parent demographic variables, the largest contributors to the prediction of
      parent wellbeing were parent problem solving ability, access to resources,
      environmental/social supports, and parent appraisals of threat. Child functional
      impairment was not significantly associated with parent wellbeing. CONCLUSIONS:
      Access to resources and environmental/social supports have a greater direct
      effect on parent wellbeing than parent and child demographic variables and
      disability severity. Threat appraisals have direct and mediating effects on
      parent wellbeing. Implications related to the importance of resources and
      environmental/social supports, appraisals of threat and growth, and problem
      solving abilities on the wellbeing of parents of children with disabilities are
      discussed.

PMID- 22369119
TI  - Utility of the Illness Intrusiveness Scale in parents of children diagnosed with
      juvenile rheumatic diseases.
AB  - OBJECTIVE: To examine the factor structure and convergent validity of the Illness
      Intrusiveness Scale--Parent Version in mother and fathers of children and
      adolescents ages 7 to 18 (M = 13.56 years, SD = 2.67) diagnosed with a juvenile
      rheumatic disease. DESIGN: Parents of 122 children and adolescents (82 girls, 40
      boys) completed the Illness Intrusiveness Scale-Parent Version, and both parents
      and children and adolescents completed measures of functional disability, general
      distress, and illness uncertainty. An exploratory factor analysis was conducted
      on the Illness Intrusiveness Scale--Parent Version to identify the factor
      structure. The factors were then compared with parent- and child-report measures
      of functional disability, general distress, and uncertainty. Finally, analyses
      were conducted to determine whether the magnitude of the correlations was
      significantly different between factors for parents and children and adolescents.
      RESULTS: The Illness Intrusiveness Scale--Parent Version was found to have a two
      factor structure. The Relationships/Personal Development factor contained items
      related to self-fulfillment and interactions with others, and the Instrumental
      factor contained items related to health and work. These factors were found to
      have good internal consistency and were significantly correlated with measures of
      parent-reported functional disability and parent- and youth-reported distress and
      uncertainty. The magnitude of these correlations was also found to differ
      depending on informant and outcome measure. CONCLUSION: The Illness Intrusiveness
      Scale--Parent Version appears to be a valid measure for use in parents of
      children with juvenile rheumatic disease.

PMID- 22369120
TI  - Early pharmaceutical evaluation of a crystalline and hygroscopic GABAB receptor
      agonist.
AB  - Lesogaberan is a potent gamma amino butyric acid agonist and has been evaluated
      for its utility in treatment of gastroesophageal reflux disease. Lesogaberan is a
      crystalline substance that absorbs considerable amounts of water above 65%
      relative humidity (RH) where it also liquifies. As a result of the hygroscopicity
      of the zwitterionic form an investigation of different salt forms was performed.
      Since the test compound is polar and lacks ultraviolet (UV) chromophore,
      conventional separation and detection techniques could not be used to
      characterise the test compound and the impurities. The analytical techniques are
      described, focusing on the capillary electrophoresis method with indirect UV
      detection for purity, the liquid chromatographic method for enantiomeric
      separation with derivatisation with UV chromophore and two complementary nuclear
      magnetic resonance (NMR) approaches (19F-NMR and 1H-NMR) for impurities. The
      stability study in solution showed that solutions between pH 5 and 7 were the
      most stable ones, but after some time degradation occurred at room temperature.
      When bulk lesogaberan was stored at 25 degrees C/60% RH no chemical degradation
      was observed after 1 year. At 40 degrees C/75% RH, where the compound liquefies,
      a significant degradation was observed after 1 month. However, in a closed
      container (= 40 degrees C) or as a napsylate salt, no degradation of lesogaberan
      was observed at 40 degrees C/75% RH.

PMID- 22369121
TI  - Measuring the range of plasmonic interaction.
AB  - When gold nanoparticles are covered with nanometric layers of transparent
      polyelectrolytes, the plasmon absorption spectrum A(lambda) increases by a factor
      of approximately three and shifts to the red. These modifications of dissipative
      experimental observables stop when the cover layer thickness approaches the
      particle diameter. Spectral modifications of dispersive parameters like the
      reflection R, however, keep changing with increasing cover layer thickness. The
      shift of the plasmon resonance caused by two interacting particle layers is
      studied as a function of the separating distance between the two layers. We
      discuss these observations in the context of an effective medium theory and
      conclude that it can only be applied for a layer thickness on the order of the
      particle diameter.

PMID- 22369122
TI  - Identifying regulational alterations in gene regulatory networks by state space
      representation of vector autoregressive models and variational annealing.
AB  - BACKGROUND: In the analysis of effects by cell treatment such as drug dosing,
      identifying changes on gene network structures between normal and treated cells
      is a key task. A possible way for identifying the changes is to compare
      structures of networks estimated from data on normal and treated cells
      separately. However, this approach usually fails to estimate accurate gene
      networks due to the limited length of time series data and measurement noise.
      Thus, approaches that identify changes on regulations by using time series data
      on both conditions in an efficient manner are demanded. METHODS: We propose a new
      statistical approach that is based on the state space representation of the
      vector autoregressive model and estimates gene networks on two different
      conditions in order to identify changes on regulations between the conditions. In
      the mathematical model of our approach, hidden binary variables are newly
      introduced to indicate the presence of regulations on each condition. The use of
      the hidden binary variables enables an efficient data usage; data on both
      conditions are used for commonly existing regulations, while for condition
      specific regulations corresponding data are only applied. Also, the similarity of
      networks on two conditions is automatically considered from the design of the
      potential function for the hidden binary variables. For the estimation of the
      hidden binary variables, we derive a new variational annealing method that
      searches the configuration of the binary variables maximizing the marginal
      likelihood. RESULTS: For the performance evaluation, we use time series data from
      two topologically similar synthetic networks, and confirm that our proposed
      approach estimates commonly existing regulations as well as changes on
      regulations with higher coverage and precision than other existing approaches in
      almost all the experimental settings. For a real data application, our proposed
      approach is applied to time series data from normal Human lung cells and Human
      lung cells treated by stimulating EGF-receptors and dosing an anticancer drug
      termed Gefitinib. In the treated lung cells, a cancer cell condition is simulated
      by the stimulation of EGF-receptors, but the effect would be counteracted due to
      the selective inhibition of EGF-receptors by Gefitinib. However, gene expression
      profiles are actually different between the conditions, and the genes related to
      the identified changes are considered as possible off-targets of Gefitinib.
      CONCLUSIONS: From the synthetically generated time series data, our proposed
      approach can identify changes on regulations more accurately than existing
      methods. By applying the proposed approach to the time series data on normal and
      treated Human lung cells, candidates of off-target genes of Gefitinib are found.
      According to the published clinical information, one of the genes can be related
      to a factor of interstitial pneumonia, which is known as a side effect of
      Gefitinib.

PMID- 22369123
TI  - Late blight resistance gene from Solanum ruiz-ceballosii is located on potato
      chromosome X and linked to violet flower colour.
AB  - BACKGROUND: Phytophthora infestans (Mont.) de Bary, the causal organism of late
      blight, is economically the most important pathogen of potato and resistance
      against it has been one of the primary goals of potato breeding. Some potentially
      durable, broad-spectrum resistance genes against this disease have been described
      recently. However, to obtain durable resistance in potato cultivars more genes
      are needed to be identified to realize strategies such as gene pyramiding or use
      of genotype mixtures based on diverse genes. RESULTS: A major resistance gene,
      Rpi-rzc1, against P. infestans originating from Solanum ruiz-ceballosii was
      mapped to potato chromosome X using Diversity Array Technology (DArT) and
      sequence-specific PCR markers. The gene provided high level of resistance in both
      detached leaflet and tuber slice tests. It was linked, at a distance of 3.4 cM,
      to violet flower colour most likely controlled by the previously described F
      locus. The marker-trait association with the closest marker, violet flower
      colour, explained 87.1% and 85.7% of variance, respectively, for mean detached
      leaflet and tuber slice resistance. A genetic linkage map that consisted of 1,603
      DArT markers and 48 reference sequence-specific PCR markers of known chromosomal
      localization with a total map length of 1204.8 cM was constructed. CONCLUSIONS:
      The Rpi-rzc1 gene described here can be used for breeding potatoes resistant to
      P. infestans and the breeding process can be expedited using the molecular
      markers and the phenotypic marker, violet flower colour, identified in this
      study. Knowledge of the chromosomal localization of Rpi-rzc1 can be useful for
      design of gene pyramids. The genetic linkage map constructed in this study
      contained 1,149 newly mapped DArT markers and will be a valuable resource for
      future mapping projects using this technology in the Solanum genus.

PMID- 22369124
TI  - Impacts and recovery of the Deepwater Horizon oil spill on vegetation structure
      and function of coastal salt marshes in the northern Gulf of Mexico.
AB  - We investigated the impacts of the Deepwater Horizon (DWH) oil spill on two
      dominant coastal saltmarsh plants, Spartina alterniflora and Juncus roemerianus,
      in the northern Gulf of Mexico and the processes controlling differential species
      effects and recovery. Seven months after the Macondo MC 252 oil made landfall
      along the shoreline salt marshes of northern Barataria Bay, Louisiana,
      concentrations of total petroleum hydrocarbons in the surface 2 cm of heavily
      oiled marsh soils were as high as 510 mg g(-1). Heavy oiling caused almost
      complete mortality of both species. However, moderate oiling impacted Spartina
      less severely than Juncus and, relative to the reference marshes, had no
      significant effect on Spartina while significantly lowering live aboveground
      biomass and stem density of Juncus. A greenhouse mesocosm study supported field
      results and indicated that S. alterniflora was much more tolerant to shoot oil
      coverage than J. roemerianus. Spartina recovered from as much as 100% oil
      coverage of shoots in 7 months; however, Juncus recovered to a much lesser
      extent. Soil-oiling significantly affected both species. Severe impacts of the
      Macondo oil to coastal marsh vegetation most likely resulted from oil exposure of
      the shoots and oil contact on/in the marsh soil, as well as repeated oiling
      events.

PMID- 22369126
TI  - Planarized triarylboranes: stabilization by structural constraint and their plane
      to-bowl conversion.
AB  - Triphenylborane and 9,10-diphenyl-9,10-dihydro-9,10-diboraanthracene, constrained
      to a planar arrangement with methylene tethers, were synthesized by
      intramolecular multi-fold Friedel-Crafts cyclization. These compounds were stable
      toward air, water, and amines, despite the absence of steric protection in the
      vertical direction with respect to the B atoms, and showed characteristic
      structural, electronic, and photophysical properties. In addition, upon treatment
      with a fluoride ion, these compounds underwent a plane-to-bowl conversion in a
      controlled manner.

PMID- 22369125
TI  - A high performance liquid chromatographic assay of mefloquine in saliva after a
      single oral dose in healthy adult Africans.
AB  - BACKGROUND: Mefloquine-artesunate is a formulation of artemisinin based
      combination therapy (ACT) recommended by the World Health Organization and
      historically the first ACT used clinically. The use of ACT demands constant
      monitoring of therapeutic efficacies and drug levels, in order to ensure that
      optimum drug exposure is achieved and detect reduced susceptibility to these
      drugs. Quantification of anti-malarial drugs in biological fluids other than
      blood would provide a more readily applicable method of therapeutic drug
      monitoring in developing endemic countries. Efforts in this study were devoted to
      the development of a simple, field applicable, non-invasive method for assay of
      mefloquine in saliva. METHODS: A high performance liquid chromatographic method
      with UV detection at 220 nm for assaying mefloquine in saliva was developed and
      validated by comparing mefloquine concentrations in saliva and plasma samples
      from four healthy volunteers who received single oral dose of mefloquine.
      Verapamil was used as internal standard. Chromatographic separation was achieved
      using a Hypersil ODS column. RESULTS: Extraction recoveries of mefloquine in
      plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of
      mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine
      concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma
      concentrations ratio was 0.42. CONCLUSION: Disposition of mefloquine in saliva
      paralleled that in plasma, making salivary quantification of mefloquine
      potentially useful in therapeutic drug monitoring.

PMID- 22369127
TI  - Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase
      inhibitors.
AB  - Mycobacterium tuberculosis glutamine synthetase (MtGS) is a promising target for
      antituberculosis drug discovery. In a recent high-throughput screening study we
      identified several classes of MtGS inhibitors targeting the ATP-binding site. We
      now explore one of these classes, the 2-tert-butyl-4,5-diarylimidazoles, and
      present the design, synthesis, and X-ray crystallographic studies leading to the
      identification of MtGS inhibitors with submicromolar IC(50) values and promising
      antituberculosis MIC values.

PMID- 22369128
TI  - APOC3 and PNPLA3 in non-alcoholic fatty liver disease: need to clear the air.

PMID- 22369130
TI  - Biochemical increase in phosphorylated alpha-synuclein precedes histopathology of
      Lewy-type synucleinopathies.
AB  - A key component in Lewy body (LB) pathology in LB disorders is alpha-synuclein
      phosphorylated at serine 129 (palphasyn). However, it is not known if increase in
      the level of biochemically measurable palphasyn precedes the presence of
      histologically identified Lewy-type synucleinopathy (LTS). To gain sights into
      possible temporal sequence, we measured levels of palphasyn in cingulate and
      temporal cortices that develop LTS pathology at later stages of LB disorders.
      Brain homogenates from 128 autopsy cases including normal controls and subjects
      classified by Unified LTS histopathology staging system were studied. We found
      that biochemically measurable palphasyn levels in cingulate and temporal cortices
      were significantly increased at Unified stages III and IV. When palphasyn levels
      were compared between LTS density scores instead of Unified stages, significant
      increases were detected even as LTS density scores increased from 0 to 1 in
      olfactory bulb and substantia nigra. Therefore, our findings demonstrated that
      changes of palphasyn levels in cingulate and temporal cortices coincided with the
      early appearance of the LTS pathology in olfactory bulb and substantia nigra,
      even though histologically demonstrable LTS was lacking in the cortical region.
      Therefore, identifying the underlying mechanisms driving these changes could be
      crucial to understanding the pathogenesis of LB disorders.

PMID- 22369131
TI  - Partial response of angiosarcoma of the scalp to sorafenib: association with
      decreased expression of vascular endothelial growth factors and their receptors.
AB  - The prognosis of angiosarcoma remains very poor, even with combined, multimodal
      therapy. We report a case with partial response of angiosarcoma of the scalp to
      sorafenib, which is a new oral, molecular, targeted, multiple-kinase inhibitor.
      In addition, we confirmed, using immunohistochemistry, that sorafenib suppressed
      the expression of vascular endothelial growth factors and their receptors on the
      angiosarcoma tumour cells, and decreased cell numbers by inhibiting cellular
      proliferation.

PMID- 22369132
TI  - Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine
      responsive megaloblastic anaemia.
AB  - Permanent neonatal diabetes mellitus (PNDM) is diagnosed within the first 6
      months of life, and is usually monogenic in origin. Heterozygous mutations in
      ABCC8, KCNJ11, and INS genes account for around half of cases of PNDM; mutations
      in 10 further genes account for a further 10%, and the remaining 40% of cases are
      currently without a molecular genetic diagnosis. Thiamine-responsive
      megaloblastic anaemia (TRMA), due to mutations in the thiamine transporter
      SLC19A2, is associated with the classical clinical triad of diabetes, deafness,
      and megaloblastic anaemia. Diabetes in this condition is well described in
      infancy but has only very rarely been reported in association with neonatal
      diabetes. We used a combination of homozygosity mapping and evaluation of
      clinical information to identify cases of TRMA from our cohort of patients with
      PNDM. Homozygous mutations in SLC19A2 were identified in three cases in which
      diabetes presented in the first 6 months of life, and a further two cases in
      which diabetes presented between 6 and 12 months of age. We noted the presence of
      a significant neurological disorder in four of the five cases in our series,
      prompting us to examine the incidence of these and other non-classical clinical
      features in TRMA. From 30 cases reported in the literature, we found significant
      neurological deficit (stroke, focal, or generalized epilepsy) in 27%, visual
      system disturbance in 43%, and cardiac abnormalities in 27% of cases. TRMA should
      be considered in the differential diagnosis of diabetes presenting in the
      neonatal period.

PMID- 22369133
TI  - Maximizing biomarker discovery by minimizing gene signatures.
AB  - BACKGROUND: The use of gene signatures can potentially be of considerable value
      in the field of clinical diagnosis. However, gene signatures defined with
      different methods can be quite various even when applied the same disease and the
      same endpoint. Previous studies have shown that the correct selection of subsets
      of genes from microarray data is key for the accurate classification of disease
      phenotypes, and a number of methods have been proposed for the purpose. However,
      these methods refine the subsets by only considering each single feature, and
      they do not confirm the association between the genes identified in each gene
      signature and the phenotype of the disease. We proposed an innovative new method
      termed Minimize Feature's Size (MFS) based on multiple level similarity analyses
      and association between the genes and disease for breast cancer endpoints by
      comparing classifier models generated from the second phase of MicroArray Quality
      Control (MAQC-II), trying to develop effective meta-analysis strategies to
      transform the MAQC-II signatures into a robust and reliable set of biomarker for
      clinical applications. RESULTS: We analyzed the similarity of the multiple gene
      signatures in an endpoint and between the two endpoints of breast cancer at probe
      and gene levels, the results indicate that disease-related genes can be
      preferably selected as the components of gene signature, and that the gene
      signatures for the two endpoints could be interchangeable. The minimized
      signatures were built at probe level by using MFS for each endpoint. By applying
      the approach, we generated a much smaller set of gene signature with the similar
      predictive power compared with those gene signatures from MAQC-II. CONCLUSIONS:
      Our results indicate that gene signatures of both large and small sizes could
      perform equally well in clinical applications. Besides, consistency and
      biological significances can be detected among different gene signatures,
      reflecting the studying endpoints. New classifiers built with MFS exhibit
      improved performance with both internal and external validation, suggesting that
      MFS method generally reduces redundancies for features within gene signatures and
      improves the performance of the model. Consequently, our strategy will be
      beneficial for the microarray-based clinical applications.

PMID- 22369134
TI  - Origin of multiple periodicities in the Fourier power spectra of the Plasmodium
      falciparum genome.
AB  - BACKGROUND: Fourier transforms and their associated power spectra are used for
      detecting periodicities and protein-coding genes and is generally regarded as a
      well established technique. Many of the periodicities which have been found with
      this method are quite well understood such as the periodicity of 3 nt which is
      associated to codon usage. But what is the origin of the peculiar frequency
      multiples k/21 which were reported for a tiny section of chromosome 2 in P.
      falciparum? Are these present in other chromosomes and perhaps in related
      organisms? And how should we interpret fractional periodicities in genomes?
      RESULTS: We applied the binary indicator power spectrum to all chromosomes of P.
      falciparum, and found that the frequency overtones k/21 are present only in non
      coding sections. We did not find such frequency overtones in any other related
      genomes. Furthermore, the frequency overtones were identified as artifacts of the
      way the genome is encoded into a numerical sequence, that is, they are frequency
      aliases. By choosing a different way to encode the sequence the overtones do not
      appear. In view of these results, we revisited early applications of this
      technique to proteins where frequency overtones were reported. CONCLUSIONS: Some
      authors hinted recently at the possibility of mapping artifacts and frequency
      aliases in power spectra. However, in the case of P. falciparum the frequency
      aliases are particularly strong and can mask the 1/3 frequency which is used for
      gene detecting. This shows that albeit being a well known technique, with a long
      history of application in proteins, few researchers seem to be aware of the
      problems represented by frequency aliases.

PMID- 22369135
TI  - Food groups and nutrient intake and risk of colorectal cancer: a hospital-based
      case-control study in Spain.
AB  - Although evidence supports that colorectal cancer (CRC) has an environmental
      etiology, the potential influence of diet appears to be one of the most important
      components. We studied the relation between food groups and nutrient intake and
      the risk of CRC. A hospital-based case-control study was conducted in Spain
      between 2007 and 2009. The authors matched 245 patients with incident
      histologically confirmed CRC by age, gender, and date of admission with 490
      controls. Information about nutrient intake was gathered by using a
      semiquantitative frequency food questionnaire. Univariate analysis was done with
      individual food items. Odds ratios (ORs) for consecutive tertiles of nutrient
      intake were computed after allowance for sociodemographic variables and
      consumption of food groups. Vitamin B6 (OR: 0.26), vitamin D (OR: 0.45), vitamin
      E (OR: 0.42), polyunsaturated fatty acids (OR: 0.57), and fiber (OR: 0.40) were
      inversely associated with CRC, whereas carbohydrates (OR: 1.82) were
      significantly associated with CRC risk for the upper tertile. In multivariate
      analysis adjusting for major covariables (energy, age, and gender), vitamin D
      (OR:0.45), vitamin E (OR:0.36), and fiber (OR:0.46) remained associated with CRC.
      Data suggest that the etiology of colorectal cancer is not due to lifestyle and
      dietary patterns being important the effect of single nutrients.

PMID- 22369137
TI  - Synthesis of the core of actinophyllic acid using a transannular acyl radical
      cyclization.
AB  - A synthetic study of actinophyllic acid based on an original strategy has been
      described. A transannular acyl radical cyclization allowed us to obtain a key
      bicyclo[3.3.2] framework, and construction of a core of the target alkaloid has
      been accomplished by subsequent introduction of a C2 unit.

PMID- 22369138
TI  - Diffusion of oxygen in cork.
AB  - This work reports measurements of effective oxygen diffusion coefficient in raw
      cork. Kinetics of oxygen transfer through cork is studied at 298 K thanks to a
      homemade manometric device composed of two gas compartments separated by a cork
      wafer sample. The first compartment contains oxygen, whereas the second one is
      kept under dynamic vacuum. The pressure decrease in the first compartment is
      recorded as a function of time. The effective diffusion coefficient D(eff) is
      obtained by applying Fick's law to transient state using a numerical method based
      on finite differences. An analytical model derived from Fick's law applied to
      steady state is also proposed. Results given by these two methods are in close
      agreement with each other. The harmonic average of the effective diffusion
      coefficients obtained from the distribution of 15 cork wafers of 3 mm thickness
      is 1.1 * 10(-9) m(2) s(-1) with a large distribution over four decades. The
      statistical analysis of the Gaussian distribution obtained on a 3 mm cork wafer
      is extrapolated to a 48 mm cork wafer, which length corresponds to a full cork
      stopper. In this case, the probability density distribution gives a mean value of
      D(eff) equal to 1.6 * 10(-9) m(2) s(-1). This result shows that it is possible to
      obtain the effective diffusion coefficient of oxygen through cork from short time
      (few days) measurements performed on a thin cork wafer, whereas months are
      required to obtain the diffusion coefficient for a full cork stopper.
      Permeability and oxygen transfer rate are also calculated for comparison with
      data from other studies.

PMID- 22369139
TI  - Precise mid-trimester placenta localisation: does it predict adverse outcomes?
AB  - BACKGROUND: A low-lying placenta detected at the mid-pregnancy ultrasound is
      commonly reported to warn against potential morbidity associated with placenta
      praevia. There is no information on what distance away from the internal cervical
      os is safe. AIMS: We examined whether a low-lying placenta not overlapping the
      cervical os in the second trimester increases the risk of obstetric complications
      and whether there is a cut-off point at which that increase occurs. METHODS:
      Adverse perinatal outcomes were examined prospectively in a cohort of women with
      a placenta 0-30 mm from the internal cervical os ('low-lying') at the routine mid
      trimester ultrasound and compared to those with a placenta further away. Two
      composite outcomes of 'major' and 'minor' adverse events were predefined as
      primary outcome measures, requiring a sample size of 480 women with a low-lying
      placenta. Chi-square and Fisher's exact tests were used for statistical analysis.
      RESULTS: In 1662 pregnancies ('low-lying': n = 484; 'normal': n = 1178), there
      was no increase in composite adverse outcomes with a low-lying placenta and no
      cut-off distance within 30 mm from the cervical os at which risks increased.
      Postpartum haemorrhage >= 1000 mL was more frequent with a low-lying placenta
      (7.6% vs 4.7%, P < 0.05). CONCLUSIONS: Women with a low-lying placenta, not
      overlapping the cervical os, in mid-pregnancy are at no higher risk of adverse
      outcomes than those with a normally located placenta, except postpartum
      haemorrhage. This suggests that the high-risk label can be removed from
      pregnancies with a low-lying placenta not overlapping the cervical os in mid
      pregnancy, reducing anxiety and resource utilisation.

PMID- 22369136
TI  - Thiol-redox signaling, dopaminergic cell death, and Parkinson's disease.
AB  - SIGNIFICANCE: Parkinson's disease (PD) is characterized by the selective loss of
      dopaminergic neurons of the substantia nigra pars compacta, which has been widely
      associated with oxidative stress. However, the mechanisms by which redox
      signaling regulates cell death progression remain elusive. RECENT ADVANCES: Early
      studies demonstrated that depletion of glutathione (GSH), the most abundant low
      molecular-weight thiol and major antioxidant defense in cells, is one of the
      earliest biochemical events associated with PD, prompting researchers to
      determine the role of oxidative stress in dopaminergic cell death. Since then,
      the concept of oxidative stress has evolved into redox signaling, and its
      complexity is highlighted by the discovery of a variety of thiol-based redox
      dependent processes regulating not only oxidative damage, but also the activation
      of a myriad of signaling/enzymatic mechanisms. CRITICAL ISSUES: GSH and GSH-based
      antioxidant systems are important regulators of neurodegeneration associated with
      PD. In addition, thiol-based redox systems, such as peroxiredoxins, thioredoxins,
      metallothioneins, methionine sulfoxide reductases, transcription factors, as well
      as oxidative modifications in protein thiols (cysteines), including cysteine
      hydroxylation, glutathionylation, and nitrosylation, have been demonstrated to
      regulate dopaminergic cell loss. FUTURE DIRECTIONS: In this review, we summarize
      major advances in the understanding of the role of thiol-redox signaling in
      dopaminergic cell death in experimental PD. Future research is still required to
      clearly understand how integrated thiol-redox signaling regulates the activation
      of the cell death machinery, and the knowledge generated should open new avenues
      for the design of novel therapeutic approaches against PD.

PMID- 22369140
TI  - Prioritizing disease candidate genes by a gene interconnectedness-based approach.
AB  - BACKGROUND: Genome-wide disease-gene finding approaches may sometimes provide us
      with a long list of candidate genes. Since using pure experimental approaches to
      verify all candidates could be expensive, a number of network-based methods have
      been developed to prioritize candidates. Such tools usually have a set of
      parameters pre-trained using available network data. This means that re-training
      network-based tools may be required when existing biological networks are updated
      or when networks from different sources are to be tried. RESULTS: We developed a
      parameter-free method, interconnectedness (ICN), to rank candidate genes by
      assessing the closeness of them to known disease genes in a network. ICN was
      tested using 1,993 known disease-gene associations and achieved a success rate of
      ~44% using a protein-protein interaction network under a test scenario of
      simulated linkage analysis. This performance is comparable with those of other
      well-known methods and ICN outperforms other methods when a candidate disease
      gene is not directly linked to known disease genes in a network. Interestingly,
      we show that a combined scoring strategy could enable ICN to achieve an even
      better performance (~50%) than other methods used alone. CONCLUSIONS: ICN, a user
      friendly method, can well complement other network-based methods in the context
      of prioritizing candidate disease genes.

PMID- 22369141
TI  - Association between ghrelin gene (GHRL) polymorphisms and clinical response to
      atypical antipsychotic drugs in Han Chinese schizophrenia patients.
AB  - BACKGROUND: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy
      balance, and body mass. Weight gain (WG) is a common side effect of the atypical
      antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms
      have been associated with pathogenic variations in plasma lipid concentrations,
      blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear
      whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there
      is no evidence of an association between GHRL polymorphisms and SZ or the
      therapeutic response to AAPs. We explored these potential associations by
      genotyping GHRL alleles in SZ patients and controls. We also examined the
      relation between these SNPs and changes in metabolic indices during AAP treatment
      in SZ subgroups distinguished by high or low therapeutic response. METHODS: Four
      SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634
      schizophrenia patients and 606 control subjects. RESULTS: There were no
      significant differences in allele frequencies, genotype distributions, or the
      distributions of two SNP haplotypes between SZ patients and healthy controls (P >
      0.05). There was also no significant difference in symptom reduction between
      genotypes after 8 weeks of AAP treatment as measured by positive and negative
      symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated
      with a greater BMI increase in response to AAP administration in both APP
      responders and non-responders as distinguished by PANSS score reduction (P <
      0.001). There were also significant differences in WG when the responder group
      was further subdivided according to the specific AAP prescribed (P < 0.05).
      CONCLUSIONS: These four GHRL gene SNPs were not associated with SZ in this
      Chinese Han population. The -604 G/A polymorphism was associated with significant
      BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed
      greater improvements in positive and negative symptoms than patients exhibiting
      lower weight gain or weight loss.

PMID- 22369143
TI  - A mixture framework for inferring ancestral gene orders.
AB  - BACKGROUND: Inferring gene orders of ancestral genomes has the potential to
      provide detailed information about the recent evolution of species descended from
      them. Current popular tools to infer ancestral genome data (such as GRAPPA and
      MGR) are all parsimony-based direct optimization methods with the aim to minimize
      the number of evolutionary events. Recently a new method based on the approach of
      maximum likelihood is proposed. The current implementation of these direct
      optimization methods are all based on solving the median problems and achieve
      more accurate results than the maximum likelihood method. However, both GRAPPA
      and MGR are extremely time consuming under high rearrangement rates. The maximum
      likelihood method, on the contrary, runs much faster with less accurate results.
      RESULTS: We propose a mixture method to optimize the inference of ancestral gene
      orders. This method first uses the maximum likelihood approach to identify gene
      adjacencies that are likely to be present in the ancestral genomes, which are
      then fixed in the branch-and-bound search of median calculations. This hybrid
      approach not only greatly speeds up the direct optimization methods, but also
      retains high accuracy even when the genomes are evolutionary very distant.
      CONCLUSIONS: Our mixture method produces more accurate ancestral genomes compared
      with the maximum likelihood method while the computation time is far less than
      that of the parsimony-based direct optimization methods. It can effectively deal
      with genome data of relatively high rearrangement rates which is hard for the
      direct optimization methods to solve in a reasonable amount of time, thus extends
      the range of data that can be analyzed by the existing methods.

PMID- 22369142
TI  - Fine mapping of a linkage peak with integration of lipid traits identifies novel
      coronary artery disease genes on chromosome 5.
AB  - BACKGROUND: Coronary artery disease (CAD), and one of its intermediate risk
      factors, dyslipidemia, possess a demonstrable genetic component, although the
      genetic architecture is incompletely defined. We previously reported a linkage
      peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for
      linkage was increased in families with higher mean low density lipoprotein
      cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association
      mapping of LDL-C as an intermediate disease-related trait to further define the
      etiology of this linkage peak. The study populations consisted of 1908
      individuals from the CATHGEN biorepository of patients undergoing cardiac
      catheterization; 254 families (N = 827 individuals) from the GENECARD familial
      study of early-onset CAD; and 162 aorta samples harvested from deceased donors.
      Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per
      20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one
      SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and
      genotyped on all samples using a custom Illumina array. Association analysis of
      each SNP with LDL-C was performed using multivariable linear regression (CATHGEN)
      and the quantitative trait transmission disequilibrium test (QTDT; GENECARD).
      SNPs associated with the intermediate quantitative trait, LDL-C, were then
      assessed for association with CAD (i.e., a qualitative phenotype) using linkage
      and association in the presence of linkage (APL; GENECARD) and logistic
      regression (CATHGEN and aortas). RESULTS: We identified four genes with SNPs that
      showed the strongest and most consistent associations with LDL-C and CAD: EBF1,
      PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of
      SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005;
      SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most
      significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604,
      p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003.
      CONCLUSION: Using an intermediate disease-related quantitative trait of LDL-C we
      have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These
      four genes should be further examined in future functional studies as candidate
      susceptibility loci for cardiovascular disease mediated through LDL-cholesterol
      pathways.

PMID- 22369144
TI  - Critical review of Pd-based catalytic treatment of priority contaminants in
      water.
AB  - Catalytic reduction of water contaminants using palladium (Pd)-based catalysts
      and hydrogen gas as a reductant has been extensively studied at the bench-scale,
      but due to technical challenges it has only been limitedly applied at the field
      scale. To motivate research that can overcome these technical challenges, this
      review critically analyzes the published research in the area of Pd-based
      catalytic reduction of priority drinking water contaminants (i.e., halogenated
      organics, oxyanions, and nitrosamines), and identifies key research areas that
      should be addressed. Specifically, the review summarizes the state of knowledge
      related to (1) proposed reaction pathways for important classes of contaminants,
      (2) rates of contaminant reduction with different catalyst formulations, (3) long
      term sustainability of catalyst activity with respect to natural water foulants
      and regeneration strategies, and (4) technology applications. Critical barriers
      hindering implementation of the technology are related to catalyst activity (for
      some contaminants), stability, fouling, and regeneration. New developments
      overcoming these limitations will be needed for more extensive field-scale
      application of this technology.

PMID- 22369145
TI  - Modulated release of 5-fluorouracil from pH-sensitive and colon targeted pellets:
      an industrially feasible approach.
AB  - Pellets, reliant on pH-sensitivity and time-dependency for drug delivery, provide
      one of the most versatile opportunities for targeting colon. 5-Fluorouracil (5
      FU) loaded pellets were prepared by extrusion-spheronization using Avicel((r))
      PH101 as a spheronization aid and hydroxypropylmethylcellulose K4M (HPMC K4M)
      solution as a binder. A 3(2) full factorial design was employed to optimize
      spheronization speed and time. Obtained pellets were evaluated for flow
      properties, pellet size, roundness and aspect ratio. Optimized batch was coated
      in a bottom-spray fluidized bed processor (FBP) with an inner coat of sustained
      release polymer Eudragit NE30D and an outer coat of pH-sensitive polymer Eudragit
      FS30D. The coating levels were statistically optimized and in vitro drug release
      was monitored by changing pH media method. Optimized system with 15% inner and
      outer coating levels revealed t(50%) (time required for 50% drug release) to be
      about 9 h while almost complete drug was released in 24 h (98.71 +/- 1.33%) with
      highest dissolution efficiency (DE(24h)) of 58.71%. The optimization model was
      validated; the predicted and experimental/actual values for validation batch (M1)
      were in close tolerance and the standard error (SE) was also small. Drug release
      was also studied at pH 7.4. Scanning electron microscopy (SEM) demonstrated
      average coating thickness to be 32.50 +/- 3.0 um. Hence, the present study
      provides constructive results for colon targeting of 5-FU pellets with
      industrially feasible processes.

PMID- 22369146
TI  - The case of Iranian immigrants in the greater Toronto area: a qualitative study.
AB  - INTRODUCTION: Iranians comprise an immigrant group that has a very different
      cultural background from that of the mainstream Canadian population and speaks a
      language other than English or French; in this case mainly Farsi (Persian).
      Although Iranian immigrants in Toronto receive a high proportion of care from
      Farsi-speaking family physicians and health care providers than physicians who
      cannot speak Farsi, they are still not satisfied with the provided services. The
      purpose of this study was to identify the obstacles and issues Iranian immigrants
      faced in accessing health care services as seen through the eyes of Iranian
      health care professionals/providers and social workers working in Greater Toronto
      Area, Canada. METHODS: Narrative inquiry was used to capture and understand the
      obstacles this immigrant population faces when accessing health care services,
      through the lens of fifty Iranian health care professionals/providers and social
      workers. Thirty three health care professionals and five social workers were
      interviewed. To capture the essence of issues, individual interviews were
      followed by three focus groups consisting of three health care professionals and
      one social worker in each group. RESULTS: Three major themes emerged from the
      study: language barrier and the lack of knowledge of Canadian health care
      services/systems; lack of trust in Canadian health care services due to financial
      limitations and fear of disclosure; and somatization and needs for psychological
      supports. CONCLUSION: Iranians may not be satisfied with the Canadian health care
      services due to a lack of knowledge of the system, as well as cultural
      differences when seeking care, such as fear of disclosure, discrimination, and
      mistrust of primary care. To attain equitable, adequate, and effective access to
      health care services, immigrants need to be educated and informed about the
      Canadian health care system and services it provides. It would be of great
      benefit to this population to hold workshops on health topics, and mental health
      issues, build strong ties with the community by increasing their involvement, use
      plain language, design informative and health related websites in both Farsi and
      English, and provide a Farsi speaking telephone help line to answer their health
      related issues.

PMID- 22369148
TI  - Real-time assessment of black carbon pollution in Indian households due to
      traditional and improved biomass cookstoves.
AB  - Use of improved (biomass) cookstoves (ICs) has been widely proposed as a Black
      Carbon (BC) mitigation measure with significant climate and health benefits. ICs
      encompass a range of technologies, including natural draft (ND) stoves, which
      feature structural modifications to enhance air flow, and forced draft (FD)
      stoves, which additionally employ an external fan to force air into the
      combustion chamber. We present here, under Project Surya, the first real-time in
      situ Black Carbon (BC) concentration measurements from five commercial ICs and a
      traditional (mud) cookstove for comparison. These experiments reveal four
      significant findings about the tested stoves. First, FD stoves emerge as the
      superior IC technology, reducing plume zone BC concentration by a factor of 4
      (compared to 1.5 for ND). Indoor cooking-time BC concentrations, which varied
      from 50 to 1000 MUg m(-3) for the traditional mud cookstove, were reduced to 5
      100 MUg m(-3) by the top-performing FD stove. Second, BC reductions from IC
      models in the same technology category vary significantly: for example, some ND
      models occasionally emit more BC than a traditional cookstove. Within the ND
      class, only microgasification stoves were effective in reducing BC. Third, BC
      concentration varies significantly for repeated cooking cycles with same stove
      (standard deviation up to 50% of mean concentration) even in a standardized
      setup, highlighting inherent uncertainties in cookstove performance. Fourth, use
      of mixed fuel (reflective of local practices) increases plume zone BC
      concentration (compared to hardwood) by a factor of 2 to 3 across ICs.

PMID- 22369147
TI  - 3-aminopiperidine-based peptide analogues as the first selective noncovalent
      inhibitors of the bacterial cysteine protease IdeS.
AB  - A series of eight peptides corresponding to the amino acid sequence of the hinge
      region of IgG and 17 newly synthesized peptide analogues containing a piperidine
      moiety as a replacement of a glycine residue were tested as potential inhibitors
      of the bacterial IgG degrading enzyme of  Streptococcus pyogenes , IdeS. None of
      the peptides showed any inhibitory activity of IdeS, but several piperidine-based
      analogues were identified as inhibitors. Two different analysis methods were
      used: an SDS-PAGE based assay to detect IgG cleavage products and a surface
      plasmon resonance spectroscopy based assay to quantify the degree of inhibition.
      To investigate the selectivity of the inhibitors for IdeS, all compounds were
      screened against two other related cysteine proteases (SpeB and papain). The
      selectivity results show that larger analogues that are active inhibitors of IdeS
      are even more potent as inhibitors of papain, whereas smaller analogues that are
      active inhibitors of IdeS inhibit neither SpeB nor papain. Two compounds were
      identified that exhibit high selectivity against IdeS and will be used for
      further studies.

PMID- 22369149
TI  - A gene selection method for GeneChip array data with small sample sizes.
AB  - BACKGROUND: In microarray experiments with small sample sizes, it is a challenge
      to estimate p-values accurately and decide cutoff p-values for gene selection
      appropriately. Although permutation-based methods have proved to have greater
      sensitivity and specificity than the regular t-test, their p-values are highly
      discrete due to the limited number of permutations available in very small sample
      sizes. Furthermore, estimated permutation-based p-values for true nulls are
      highly correlated and not uniformly distributed between zero and one, making it
      difficult to use current false discovery rate (FDR)-controlling methods. RESULTS:
      We propose a model-based information sharing method (MBIS) that, after an
      appropriate data transformation, utilizes information shared among genes. We use
      a normal distribution to model the mean differences of true nulls across two
      experimental conditions. The parameters of the model are then estimated using all
      data in hand. Based on this model, p-values, which are uniformly distributed from
      true nulls, are calculated. Then, since FDR-controlling methods are generally not
      well suited to microarray data with very small sample sizes, we select genes for
      a given cutoff p-value and then estimate the false discovery rate. CONCLUSION:
      Simulation studies and analysis using real microarray data show that the proposed
      method, MBIS, is more powerful and reliable than current methods. It has wide
      application to a variety of situations.

PMID- 22369150
TI  - Acute chorea and type 1 diabetes mellitus: clinical and neuroimaging findings.
AB  - The association of type 1 diabetes mellitus (T1DM) and acute chorea is rare. We
      report an 8-yr-old boy with T1DM who developed acute hemichorea-hemiballism of
      the right arm in whom magnetic resonance imaging (MRI) of the brain revealed
      hyperintense signal in putamen and considerable atrophy and focal area of gliosis
      in the right putamen. There was a deposition of deoxyhemoglobin indicating recent
      bleeding in the left lentiform nucleus. A control MRI 2 months later showed
      complete reabsorption of the blood component in the left lentiform nucleus.
      Multislice computerized tomography revealed hyperdensities in the corpus striatum
      and subcortical calcifications. This report describes, for the first time,
      findings of calcifications in the corticomedullary junction in the brain
      hemispheres of a child with T1DM and chorea and reviews the possible causal
      mechanisms of this unusual association.

PMID- 22369151
TI  - CMI editorial report 2012.

PMID- 22369152
TI  - Plague and cholera in the genomics era.

PMID- 22369153
TI  - Genomics of epidemic pathogens.
AB  - Virulence factors are thought to be responsible for the virulence capacity of
      pathogenic bacteria. However, epidemic bacteria were recently found to contain
      significantly fewer 'virulence factors' than non-epidemic species, and some of
      the most dangerous epidemic bacteria, such as Mycobacteria spp. and Rickettsia
      spp., have reduced genomes, and contain hundreds of degraded genes. Epidemic
      bacteria are actually highly specialized species, characterized by allopatric
      speciation, that, after adapting to their hosts, attempt to maintain a balance
      between gene gain and gene loss that favours gene loss, finally leading to genome
      reduction. Recent comparative genomic studies have demonstrated that the
      specialization of bacteria to eukaryotic cells is associated with massive gene
      loss. Furthermore, the 12 deadliest epidemic species for humankind have
      significantly smaller genomes, with fewer open reading frames, than less
      dangerous species. Epidemic species mostly lose genes related to metabolic
      activity, the production of energy, cell motility, and transcription. Epidemic
      bacteria also possess a damaged recombination and repair system and significantly
      more toxins than closely related non-pathogenic or non-epidemic species, and more
      toxin-antitoxin modules. Epidemic bacteria are therefore highly specialized
      species that are adapted to their hosts and characterized by extensive genome
      reduction. Except for toxins and toxin-antitoxin modules, which have a direct and
      measurable effect, other 'virulence factors' are factors associated with fitness
      in experimental models. Epidemic species are defined by a virulent genomic
      repertoire including both present and absent genes.

PMID- 22369154
TI  - Reflections on crisis burials related to past plague epidemics.
AB  - Drawing its etymology from the Latin pestis (curse), plague, over the centuries,
      has been more dreaded by humankind than any other epidemic. The Apocalypse had
      recognized plague as the archetypal divine curse, 'the power to kill over a
      fourth of the earth'. Plague is thus a particular topic of study, insofar that it
      is one of the rare epidemics that has had recurrent major consequences on
      demography and human societies. Its highly transmissible nature, the brutality of
      its action, its high pathogenicity, marked by strong lethality and great
      swiftness, and the complete absence of treatment options before the 20th century
      conferred on it a sinister aspect. Generating a series of severe demographic
      crises, well known in the Western world, it has necessarily influenced the
      evolution of societies at both the biological and cultural levels.

PMID- 22369155
TI  - Plague in the genomic area.
AB  - With plague being not only a subject of interest for historians, but still a
      disease of public health concern in several countries, mainly in Africa, there
      were hopes that analyses of the Yersinia pestis genomes would put an end to this
      deadly epidemic pathogen. Genomics revealed that Y. pestis isolates evolved from
      Yersinia pseudotuberculosis in Central Asia some millennia ago, after the
      acquisition of two Y. pestis-specific plasmids balanced genomic reduction
      parallel with the expansion of insertion sequences, illustrating the modern
      concept that, except for the acquisition of plasmid-borne toxin-encoding genes,
      the increased virulence of Y. pestis resulted from gene loss rather than gene
      acquisition. The telluric persistence of Y. pestis reminds us of this close
      relationship, and matters in terms of plague epidemiology. Whereas biotype
      Orientalis isolates spread worldwide, the Antiqua and Medievalis isolates showed
      more limited expansion. In addition to animal ectoparasites, human ectoparasites
      such as the body louse may have participated in this expansion and in devastating
      historical epidemics. The recent analysis of a Black Death genome indicated that
      it was more closely related to the Orientalis branch than to the Medievalis
      branch. Modern Y. pestis isolates grossly exhibit the same gene content, but
      still undergo micro-evolution in geographically limited areas by differing in the
      genome architecture, owing to inversions near insertion sequences and the
      stabilization of the YpfPhi prophage in Orientalis biotype isolates. Genomics
      have provided several new molecular tools for the genotyping and
      phylogeographical tracing of isolates and description of plague foci. However,
      genomics and post-genomics approaches have not yet provided new tools for the
      prevention, diagnosis and management of plague patients and the plague epidemics
      still raging in some sub-Saharan countries.

PMID- 22369157
TI  - Total synthesis of (-)-anisatin.
AB  - A novel synthetic route to (-)-anisatin has been developed. Our synthesis
      features a rhodium-catalyzed 1,4-addition of an arylboronic acid, an
      intramolecular Diels-Alder reaction of an ortho-quinone monoketal, a
      stereoselective [2,3]-Wittig rearrangement, and construction of the oxabicyclo
      [3.3.1] skeleton via cleavage of an epoxide by a primary amide.

PMID- 22369158
TI  - AlgaGEM--a genome-scale metabolic reconstruction of algae based on the
      Chlamydomonas reinhardtii genome.
AB  - BACKGROUND: Microalgae have the potential to deliver biofuels without the
      associated competition for land resources. In order to realise the rates and
      titres necessary for commercial production, however, system-level metabolic
      engineering will be required. Genome scale metabolic reconstructions have
      revolutionized microbial metabolic engineering and are used routinely for in
      silico analysis and design. While genome scale metabolic reconstructions have
      been developed for many prokaryotes and model eukaryotes, the application to less
      well characterized eukaryotes such as algae is challenging not at least due to a
      lack of compartmentalization data. RESULTS: We have developed a genome-scale
      metabolic network model (named AlgaGEM) covering the metabolism for a
      compartmentalized algae cell based on the Chlamydomonas reinhardtii genome.
      AlgaGEM is a comprehensive literature-based genome scale metabolic reconstruction
      that accounts for the functions of 866 unique ORFs, 1862 metabolites, 2249 gene
      enzyme-reaction-association entries, and 1725 unique reactions. The
      reconstruction was compartmentalized into the cytoplasm, mitochondrion, plastid
      and microbody using available data for algae complemented with
      compartmentalisation data for Arabidopsis thaliana. AlgaGEM describes a
      functional primary metabolism of Chlamydomonas and significantly predicts
      distinct algal behaviours such as the catabolism or secretion rather than
      recycling of phosphoglycolate in photorespiration. AlgaGEM was validated through
      the simulation of growth and algae metabolic functions inferred from literature.
      Using efficient resource utilisation as the optimality criterion, AlgaGEM
      predicted observed metabolic effects under autotrophic, heterotrophic and
      mixotrophic conditions. AlgaGEM predicts increased hydrogen production when
      cyclic electron flow is disrupted as seen in a high producing mutant derived from
      mutational studies. The model also predicted the physiological pathway for H2
      production and identified new targets to further improve H2 yield. CONCLUSIONS:
      AlgaGEM is a viable and comprehensive framework for in silico functional analysis
      and can be used to derive new, non-trivial hypotheses for exploring this
      metabolically versatile organism. Flux balance analysis can be used to identify
      bottlenecks and new targets to metabolically engineer microalgae for production
      of biofuels.

PMID- 22369159
TI  - Hypocalcemia and hypovitaminosis D in dogs with induced endotoxemia.
AB  - BACKGROUND: Hypocalcemia is a documented electrolyte disturbance in people and
      animals with sepsis, but its mechanism is poorly understood. OBJECTIVE: To
      investigate mechanisms of hypocalcemia in dogs with experimentally induced
      endotoxemia. ANIMALS: Six healthy mixed breed dogs were included in this
      nonrandomized, placebo-controlled, crossover study. METHODS: Dogs initially were
      injected with placebo (0.9% NaCl; 1 mL, IV) and then lipopolysaccharide (LPS; 2
      MUg/kg, IV) after a 5-day washout period. Blood and urine samples were collected
      for measurement of serum total calcium (tCa), ionized calcium (iCa), total
      magnesium (tMg), ionized magnesium (iMg), parathyroid hormone (PTH), 25
      hydroxyvitamin D (vitamin D), venous blood gases, and fractional excretion (FE)
      of calcium. RESULTS: After LPS administration, body temperature increased and
      blood pressure decreased. Both iCa and tCa decreased (P < .01), but iMg was not
      significantly different between control and LPS treatments. PTH concentrations
      increased (P < .01) and vitamin D concentrations decreased (P < .01). Venous pH,
      bicarbonate, base excess, and blood glucose also decreased (P < .01). Urine tCa
      concentration was below the limit of detection for all dogs after LPS
      administration. CONCLUSIONS: Hypocalcemia occurs during endotoxemia in dogs and
      is associated with hypovitaminosis D. Hypomagnesemia, hypoparathyroidism,
      alkalosis, and increased calciuresis are not associated with hypocalcemia in
      endotoxemic dogs.

PMID- 22369160
TI  - InCoB celebrates its tenth anniversary as first joint conference with ISCB-Asia.
AB  - In 2009 the International Society for Computational Biology (ISCB) started to
      roll out regional bioinformatics conferences in Africa, Latin America and Asia.
      The open and competitive bid for the first meeting in Asia (ISCB-Asia) was
      awarded to Asia-Pacific Bioinformatics Network (APBioNet) which has been running
      the International Conference on Bioinformatics (InCoB) in the Asia-Pacific region
      since 2002. InCoB/ISCB-Asia 2011 is held from November 30 to December 2, 2011 in
      Kuala Lumpur, Malaysia. Of 104 manuscripts submitted to BMC Genomics and BMC
      Bioinformatics conference supplements, 49 (47.1%) were accepted. The strong
      showing of Asia among submissions (82.7%) and acceptances (81.6%) signals the
      success of this tenth InCoB anniversary meeting, and bodes well for the future of
      ISCB-Asia.

PMID- 22369162
TI  - The practice of surrogacy in New Zealand.
AB  - BACKGROUND: Commercial surrogacy is prohibited in New Zealand by the Human
      Assisted Reproductive Technology Act 2004 (HART Act). However, altruistic clinic
      assisted surrogacy is permitted. Couples wishing to attempt altruistic surrogacy
      must apply for approval to a statutorily appointed ethics committee. One of seven
      principles that underpin the HART Act stipulates that the needs, values and
      beliefs of Maori (NZ's indigenous population) should be considered and treated
      with respect. AIM: This paper reviews the outcomes of surrogacy applications
      since the HART Act was established and the uptake of surrogacy by Maori. METHODS:
      The authors examined the demographic data provided to the ethics committee by way
      of surrogacy applications and the outcome data provided by fertility clinics.
      This paper reviews the outcomes for surrogacy applications: the number
      accepted/declined, the number of live births, those applications discontinued and
      uptake by Maori. RESULTS: Of 104 applications for surrogacy between 2005 and
      2010, 4 (3.8%) were declined. By July 2011, of 100 approved, there have been 26
      (26%) live births; 52 (52%) were discontinued, and 22 (22%) remain ongoing. Maori
      are much less likely to utilise surrogacy. Of the 104 original applications, 9
      (8.6%) Maori women were willing to act as a surrogate, and 2 (1.9%) were intended
      mothers. 7 (6.7%) Maori were partners of a surrogate, with 2 (1.9%) intending
      mothers having Maori partners. CONCLUSIONS: The process of surrogacy applications
      is comprehensive and robust, resulting in few being declined. Further research is
      required to discover why applications are discontinued and why, despite explicit
      attempts to meet the needs of Maori, few utilise surrogacy.

PMID- 22369161
TI  - Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine
      dihydrochloride induced colon carcinogenesis: exploring the mitochondrial
      pathway.
AB  - Apoptosis is a synchronized procedure of cell death that is regulated by caspases
      and proapoptotic proteins. During apoptosis, translocation of cytochrome c, an
      electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family
      members. Cytochrome c in association with an apoptotic protease activating factor
      (Apaf), a proapoptotic protein essential for cell differentiation and procaspase
      9 form the apoptosome complex, which consecutively activates effector caspase,
      caspase-3, and coordinate the implementation of apoptosis. In the current study,
      an attempt has been made to gain insight into piroxicam, a traditional
      nonsteroidal antiinflammatory drug and c-phycocyanin, a biliprotein from
      Spirulina platensis (cyanobacterium) mediated apoptosis in DMH-induced colon
      cancer. Male Sprague-Dawley rats were segregated into 5 groups: control, DMH, DMH
      + piroxicam, DMH + c-phycocyanin, and DMH + piroxicam + c-phycocyanin. Results
      illustrated that piroxicam and c-phycocyanin treatments stimulate cytochrome c
      release by downregulating the Bcl-2 (an antiapoptotic protein) expression
      significantly, while promoting the level of Bax (a proapoptotic protein), thereby
      activating caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present
      study clearly signify that piroxicam and c-phycocyanin may mediate mitochondrial
      dependent apoptosis in DMH-induced colon cancer. Moreover, apoptosis induction
      was more apparent in the combination regimen of piroxicam and c-phycocyanin than
      the individual drugs alone.

PMID- 22369163
TI  - Introduction to the special feature on the integrated treatment of personality
      disorder.
AB  - The solid evidence that personality disorders can be treated effectively goes
      side by side with, on the one hand, sparse evidence for disorders other than
      borderline and for personality disorders co-occurrent with one another, and, on
      the other hand, with a relative lack of knowledge about the actual effective
      mechanisms of change that underpin successful psychotherapies. In this
      introduction we present the rationale for this special feature, advocating for an
      integrated treatment of personality pathology in which empirically-supported
      strategies and techniques are selected from different traditions on the basis of
      the pragmatic principle of what works.

PMID- 22369164
TI  - Psychotherapy integration in the treatment of personality disorders: a
      commentary.
AB  - Whereas research on the treatment of personality disorders over the past several
      decades has focused primarily on comparing the efficacy of various treatment
      packages associated with different theoretical models, there is increasing
      evidence that the field would benefit from focusing more attention on developing
      integrative treatments that are both informed by research and capable of
      scientific verification. The articles assembled for this special section each
      propose a different approach to integrative treatment for personality disorders.
      In this commentary, we outline a number of reasons for making such a shift to
      more integrative treatments, consider some of the potential challenges to
      integration, and discuss the different approaches to integration illustrated in
      these articles. We highlight some of the difficult tradeoffs that must be made in
      developing an integrative approach and discuss similarities and differences in
      the response to such challenges by the contributors to this special section.
      Finally, we point to several areas for future research that we believe will
      contribute to the development of increasingly effective treatments for
      individuals with personality disorders.

PMID- 22369165
TI  - Integrated treatment: a conceptual framework for an evidence-based approach to
      the treatment of personality disorder.
AB  - Evidence that various therapies are effective in treating personality disorder
      and that outcome does not differ substantially across treatments suggests that it
      is time replace concerns about the efficacy of specific therapies and which form
      of therapy to use with an evidence-based approach that combines methods that work
      from all therapies.   A framework is proposed for selecting and combining
      eclectic treatment methods and delivering them in a coordinated way. The
      framework has two components: (1). a system for conceptualizing personality
      disorder based on empirical knowledge about the structure, etiology, development,
      and stability of personality pathology to use as a guide to selecting
      interventions and planning the sequence in which they will be used; and (2), a
      model of therapeutic change based on the general literature on psychotherapy
      outcome and specific studies of PD treatments. The framework proposes that
      integrated treatment be organized around general principles of therapeutic change
      common to all effective therapies supplemented with more specific treatment
      methods taken from the different therapies as needed to tailor treatment to
      individual patients and treat specific problems and psychopathology. The
      coordinated delivery of such a diverse array of interventions is achieved by
      using a phases of treatment scheme that proposes that treatment focus on specific
      symptoms and problems is a systematic and orderly way according to their
      stability and potential for change.

PMID- 22369166
TI  - An integrated approach to psychotherapy techniques for patients with personality
      disorder.
AB  - Personality disordered patients present with multiple problem areas and potential
      targets of change. This complex clinical situation can be addressed by an
      integrated approach to the treatment by using treatment strategies and techniques
      from the various schools of therapy, sequenced and adapted to the individual
      patient. An optimal choice and sequencing of treatment techniques is organized
      around general treatment strategies (assessment and case formulation, treatment
      structuring, observing the therapeutic relationship, addressing problematic
      personality organization, and addressing sequential goals) with the severity of
      the personality disturbance in mind. The biggest threat to successful integration
      of the treatment is the reaction of severe personality disordered patients who
      lack an integrated sense of self and suffer from intense, fluctuating emotions
      that challenge an inexperienced, reactive therapist.

PMID- 22369167
TI  - General principles for treating personality disorder with a prominent
      inhibitedness trait: towards an operationalizing integrated technique.
AB  - Psychotherapists need to perform tasks such as being empathetic, performing an
      ongoing assessment of cases, self-disclosing, making explicit treatment
      contracts, validating patients' experiences and promoting awareness of
      psychological experience, if they are to be effective in treating personality
      disorder (PD). Successful therapy also requires a systematic accurate PD model.
      We suggest here that it is still unclear how, when, and according to what session
      markers therapists need to perform specific operations to maximize therapeutic
      gains. This article describes and operationalizes a step-by-step procedure for
      organizing and delivering the interventions necessary for effective outcomes,
      such as maintaining a good therapeutic relationship, increasing understanding of
      mental states, reducing symptoms and improving social adaptation. The procedure
      is illustrated by reference to the treatment of cases of emotionally overly
      constricted PDs. We include a theoretical proposal to facilitate the development
      of measures for evaluating the efficacy of therapist actions.

PMID- 22369168
TI  - Organizing awareness and increasing emotion regulation: revising chair work in
      emotion-focused therapy for borderline personality disorder.
AB  - Emotion-focused therapy (EFT) is an empirically supported treatment that may have
      potential as a stage-two treatment for borderline personality disorder (BPD).
      Specific aspects of BPD--the tendency to experience fluctuating self-states;
      weakness in meta-cognitive or reflective functioning; and the tendency for self
      states to be organized by presently occurring interpersonal processes--present
      challenges to applying some EFT interventions with this population. In
      particular, even within a highly attuned, validating and accepting empathic
      relationship, clients with BPD may have difficulty with the usual manualizations
      of chair work interventions. This is because these interventions often employ
      polarization and intensification of experience in order to activate adaptive
      alternate emotional resources and self organizations. For the client with
      borderline personality disorder, these interventions may be counter-productive,
      emotionally dysregulating and disorganizing. EFT chair work, however, also has
      the potential to provide structure to the borderline clients experience of self,
      to stimulate metacognitive awareness, provide an alive experience of the process
      of polarization, attenuate emotional activation, and increase the experience of
      self-coherence. This article describes the development of stepwise approximations
      of EFT two-chair intervention for self-critical splits. It outlines potential
      stages of two-chair work as well as intervention principles important for
      productive chair work with this population. The EFT change principles of
      awareness, expression regulation, reflection, transformation, and corrective
      experience still centrally apply. However, several additional strategies are
      discussed to scaffold clients' capacity to both experience and regulate emotion.

PMID- 22369169
TI  - Tailoring common treatment principles to fit individual personalities.
AB  - The American Psychological Association Task Force headed by Castonguay and
      Beutler (2006) distilled general treatment principles common to all therapies
      from the empirical literature. As part of this work, Critchifield and Benjamin
      (2006a, 2006b) summarized principles for treatment of personality disorder. The
      principles are pragmatic in the sense that they are based on evidence of what
      works, and clinicians are encouraged to apply them in ways that fit the unique
      presentation and needs of a given patient. An important element of the
      recommended approach is that it be coherent, well-coordinated, and agreed upon by
      the patient. Additional principles emphasize the importance of an individual's
      attachment and trauma history. A complex case example is presented to illustrate
      one way in which emphasis on an individual's relational learning history can be
      used to further refine and extend wisdom inherent in the cross-cutting principles
      and move in the direction of an integrative treatment that is closely tailored to
      specific case features. A research approach is also outlined for how to test the
      validity of principles that prescribe differential use of technique to address
      diverse patient presentations.

PMID- 22369170
TI  - Social perspective coordination in youth with borderline personality pathology.
AB  - This study investigated social perspective coordination (SPC) in youth (15-24
      year-olds) with first-presentation borderline personality disorder (BPD). SPC is
      defined as the capacity to differentiate and integrate the perspective of the
      self with the perspectives of others (Selman, Beardslee, Schultz, Krupa, &
      Podorefsky, 1986). Two groups: patients with full or sub-syndromal BPD (n = 30)
      and patients with major depressive disorder (MDD; n = 30) completed measures of
      SPC derived from the interpersonal negotiation strategies (INS) model (Selman et
      al., 1986). Compared with the MDD group, the BPD group responded to all vignettes
      with significantly lower SPC scores and SPC was a significant predictor of BPD
      status over and above self-reported, personality factors (Neuroticism and
      Agreeableness), attachment disturbance and functional impairment. These findings
      suggest that disturbances in social cognition are an important characteristic of
      individuals with BPD pathology. These difficulties extended beyond attachment
      contexts and were not limited to situations involving BPD-related themes of
      abandonment, deprivations or mistrust/abuse.

PMID- 22369173
TI  - Sorting permutations by cut-circularize-linearize-and-paste operations.
AB  - BACKGROUND: Genome rearrangements are studied on the basis of genome-wide
      analysis of gene orders and important in the evolution of species. In the last
      two decades, a variety of rearrangement operations, such as reversals,
      transpositions, block-interchanges, translocations, fusions and fissions, have
      been proposed to evaluate the differences between gene orders in two or more
      genomes. Usually, the computational studies of genome rearrangements are
      formulated as problems of sorting permutations by rearrangement operations.
      RESULT: In this article, we study a sorting problem by cut-circularize-linearize
      and-paste (CCLP) operations, which aims to find a minimum number of CCLP
      operations to sort a signed permutation representing a chromosome. The CCLP is a
      genome rearrangement operation that cuts a segment out of a chromosome,
      circularizes the segment into a temporary circle, linearizes the temporary circle
      as a linear segment, and possibly inverts the linearized segment and pastes it
      into the remaining chromosome. The CCLP operation can model many well-known
      rearrangements, such as reversals, transpositions and block-interchanges, and
      others not reported in the biological literature. In addition, it really occurs
      in the immune response of higher animals. To distinguish those CCLP operations
      from the reversal, we call them as non-reversal CCLP operations. In this study,
      we use permutation groups in algebra to design an O(deltan) time algorithm for
      solving the weighted sorting problem by CCLP operations when the weight ratio
      between reversals and non-reversal CCLP operations is 1:2, where n is the number
      of genes in the given chromosome and delta is the number of needed CCLP
      operations. CONCLUSION: The algorithm we propose in this study is very simple so
      that it can be easily implemented with 1-dimensional arrays and useful in the
      studies of phylogenetic tree reconstruction and human immune response to tumors.

PMID- 22369174
TI  - Can we see PIP(3) and hydrogen peroxide with a single probe?
AB  - A genetically encoded sensor for parallel measurements of phosphatidylinositol 3
      kinase activity and hydrogen peroxide (H(2)O(2)) levels (termed PIP-SHOW) was
      developed. Upon elevation of local phosphatidylinositol 3,4,5-trisphosphate
      (PIP(3)) concentration, the sensor translocates from the cytosol to the plasma
      membrane, while a ratiometric excitation change rapidly and simultaneously
      reports changes in the concentration of H(2)O(2). The dynamics of PIP(3) and
      H(2)O(2) generation were monitored in platelet-derived growth factor-stimulated
      fibroblasts and in T-lymphocytes after formation of an immunological synapse. We
      suggest that PIP-SHOW can serve as a prototype for many fluorescent sensors with
      combined readouts.

PMID- 22369175
TI  - Characterization of phospholipid molecular species in the edible parts of bony
      fish and shellfish.
AB  - The phospholipid molecular species of freshwater (pangasius, Nile perch, trout),
      marine fish fillets (horse mackerel, European hake, common sole, European
      anchovy, European pilchard, Atlantic mackerel) and the edible muscle foot of
      bivalves (clam, mussel, oyster) commonly available in the Italian market during
      spring and summer were characterized by means of normal-phase high performance
      liquid chromatography coupled online with positive electrospray ionization ion
      trap tandem mass spectrometry. From principal component analysis (PCA), it was
      observed that the total fatty acid profile was not suitable to differentiate
      among the shellfish genera. The fatty acid molecular combinations of
      phosphatidylcholine, the main phospholipid class, as well as phosphatidylinositol
      and phosphatidylethanolamine allowed for the differentiation of shellfish from
      the bony fishes. Phosphatidylserine and phosphatidylethanolamine plasmalogen
      profile allowed for the discrimination of each bony fish or shellfish genus since
      PS and pPE classes included a large number of fatty acid combinations that were
      specific for a fish genus or group.

PMID- 22369176
TI  - Randomized controlled study of a cosmetic treatment for mild acne.
AB  - BACKGROUND: Cosmetic products are not tested with the same rigour as medical
      treatments, but recent high-quality studies have shown significant reductions in
      changes of skin ageing with use of cosmetic antiageing products. AIM: To test
      whether a cosmetic 'anti-spot' two-step treatment containing a complex of seaweed
      derived oligosaccharide and zinc would produce a significant improvement in mild
      acne. METHODS: A double-blind, vehicle-controlled trial of this treatment was
      performed for 8 weeks on 60 age-matched participants with mild acne. They were
      divided into two groups: 30 participants were treated with vehicle control and 30
      with the active treatment containing a seaweed-derived oligosaccharide complexed
      with 0.1% zinc pyrrolidone. RESULTS: After 8 weeks, both groups had a reduction
      in comedones, papules and pustules, and this was significantly greater in the
      active than control group at 2, 4 and 8 weeks. CONCLUSIONS: Cosmetic products may
      offer some benefit for mild acne and still meet the requirements of the European
      Cosmetic Directive. In particular, the seaweed-derived oligosaccharide complexed
      with 0.1% zinc pyrrolidone used in this study produced a significant reduction in
      acne vs. a control treatment. Cosmetic companies should conduct blinded
      controlled trials of their product's efficacy and publish the results.

PMID- 22369177
TI  - A model for biased fractionation after whole genome duplication.
AB  - BACKGROUND: Paralog reduction, the loss of duplicate genes after whole genome
      duplication (WGD) is a pervasive process. Whether this loss proceeds gene by gene
      or through deletion of multi-gene DNA segments is controversial, as is the
      question of fractionation bias, namely whether one homeologous chromosome is more
      vulnerable to gene deletion than the other. RESULTS: As a null hypothesis, we
      first assume deletion events, on either homeolog, excise a geometrically
      distributed number of genes with unknown mean MU, and a number r of these events
      overlap to produce deleted runs of length l. There is a fractionation bias 0 <=
      phi <= 1 for deletions to fall on one homeolog rather than the other. The
      parameter r is a random variable with distribution pi(.). We simulate the
      distribution of run lengths l, as well as the underlying pi(.), as a function of
      MU, phi and theta, the proportion of remaining genes in duplicate form. We show
      how sampling l allows us to estimate MU and phi. The main part of this work is
      the derivation of a deterministic recurrence to calculate each pi(r) as a
      function of MU, phi and theta. CONCLUSIONS: The recurrence for pi provides a
      deeper mathematical understanding of fractionation process than simulations. The
      parameters MU and phi can be estimated based on run lengths of single-copy
      regions.

PMID- 22369180
TI  - Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic
      evidence of independent ontogenesis and implications of chromosomal imbalances in
      tumor progression.
AB  - Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified"
      RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes,
      especially in cases where morphologic diagnosis is inconclusive. This report
      describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic
      renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features
      and genetic profile of both tumors. A 67 year-old male underwent CT scans for an
      unrelated medical event. Two incidental renal lesions were found and ultimately
      removed by radical nephrectomy. The smaller lesion had multiple small cystic
      spaces lined by hobnail cells with high nuclear grade separated by fibrous
      stroma. This morphology and the expression of proximal (CD10, AMACR) and distal
      tubule cell (CK19) markers by immunohistochemistry supported the diagnosis of
      TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and
      confined to the kidney. Molecular characterization of both neoplasms using
      virtual karyotyping was performed to assess relatedness of these tumors. Low
      grade areas (Fuhrman grade 2) of the ccRCC showed loss of 3p and gains in
      chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and
      loss of 10q; the high grade areas (Fuhrman grade 3) showed several additional
      imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of
      chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct
      genomic copy number profiles and chromosomal imbalances in TCRC might be
      implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC
      with varying degrees of differentiation exemplifies the sequence of chromosomal
      imbalances acquired during tumor progression. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283.

PMID- 22369181
TI  - (Z)-2-(2-bromophenyl)-3-{[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile
      (DG172): an orally bioavailable PPARbeta/delta-selective ligand with inverse
      agonistic properties.
AB  - The ligand-regulated nuclear receptor peroxisome proliferator-activated receptor
      beta/delta (PPARbeta/delta) is a potential pharmacological target due to its role
      in disease-related biological processes. We used TR-FRET-based competitive ligand
      binding and coregulator interaction assays to screen 2693 compounds of the Open
      Chemical Repository of the NCI/NIH Developmental Therapeutics Program for
      inhibitory PPARbeta/delta ligands. One compound, (Z)-3-(4-dimethylamino-phenyl)-2
      phenyl-acrylonitrile, was used for a systematic SAR study. This led to the design
      of derivative 37, (Z)-2-(2-bromophenyl)-3-{[4-(1-methyl
      piperazine)amino]phenyl}acrylonitrile (DG172), a novel PPARbeta/delta-selective
      ligand showing high binding affinity (IC(50) = 27 nM) and potent inverse
      agonistic properties. 37 selectively inhibited the agonist-induced activity of
      PPARbeta/delta, enhanced transcriptional corepressor recruitment, and down
      regulated transcription of the PPARbeta/delta target gene Angptl4 in mouse
      myoblasts (IC(50) = 9.5 nM). Importantly, 37 was bioavailable after oral
      application to mice with peak plasma levels in the concentration range of its
      maximal inhibitory potency, suggesting that 37 will be an invaluable tool to
      elucidate the functions and therapeutic potential of PPARbeta/delta.

PMID- 22369178
TI  - The planning and control model (PCM) of motorvisual priming: reconciling
      motorvisual impairment and facilitation effects.
AB  - Previous research on dual-tasks has shown that, under some circumstances, actions
      impair the perception of action-consistent stimuli, whereas, under other
      conditions, actions facilitate the perception of action-consistent stimuli. We
      propose a new model to reconcile these contrasting findings. The planning and
      control model (PCM) of motorvisual priming proposes that action planning binds
      categorical representations of action features so that their availability for
      perceptual processing is inhibited. Thus, the perception of categorically action
      consistent stimuli is impaired during action planning. Movement control
      processes, on the other hand, integrate multi-sensory spatial information about
      the movement and, therefore, facilitate perceptual processing of spatially
      movement-consistent stimuli. We show that the PCM is consistent with a wider
      range of empirical data than previous models on motorvisual priming. Furthermore,
      the model yields previously untested empirical predictions. We also discuss how
      the PCM relates to motorvisual research paradigms other than dual-tasks.

PMID- 22369182
TI  - Using a spike-in experiment to evaluate analysis of LC-MS data.
AB  - BACKGROUND: Recent advances in liquid chromatography-mass spectrometry (LC-MS)
      technology have led to more effective approaches for measuring changes in
      peptide/protein abundances in biological samples. Label-free LC-MS methods have
      been used for extraction of quantitative information and for detection of
      differentially abundant peptides/proteins. However, difference detection by
      analysis of data derived from label-free LC-MS methods requires various
      preprocessing steps including filtering, baseline correction, peak detection,
      alignment, and normalization. Although several specialized tools have been
      developed to analyze LC-MS data, determining the most appropriate computational
      pipeline remains challenging partly due to lack of established gold standards.
      RESULTS: The work in this paper is an initial study to develop a simple model
      with "presence" or "absence" condition using spike-in experiments and to be able
      to identify these "true differences" using available software tools. In addition
      to the preprocessing pipelines, choosing appropriate statistical tests and
      determining critical values are important. We observe that individual statistical
      tests could lead to different results due to different assumptions and employed
      metrics. It is therefore preferable to incorporate several statistical tests for
      either exploration or confirmation purpose. CONCLUSIONS: The LC-MS data from our
      spike-in experiment can be used for developing and optimizing LC-MS data
      preprocessing algorithms and to evaluate workflows implemented in existing
      software tools. Our current work is a stepping stone towards optimizing LC-MS
      data acquisition and testing the accuracy and validity of computational tools for
      difference detection in future studies that will be focused on spiking peptides
      of diverse physicochemical properties in different concentrations to better
      represent biomarker discovery of differentially abundant peptides/proteins.

PMID- 22369183
TI  - Predicting sequence and structural specificities of RNA binding regions
      recognized by splicing factor SRSF1.
AB  - BACKGROUND: RNA-binding proteins (RBPs) play diverse roles in eukaryotic RNA
      processing. Despite their pervasive functions in coding and noncoding RNA
      biogenesis and regulation, elucidating the sequence specificities that define
      protein-RNA interactions remains a major challenge. Recently, CLIP-seq (Cross
      linking immunoprecipitation followed by high-throughput sequencing) has been
      successfully implemented to study the transcriptome-wide binding patterns of
      SRSF1, PTBP1, NOVA and fox2 proteins. These studies either adopted traditional
      methods like Multiple EM for Motif Elicitation (MEME) to discover the sequence
      consensus of RBP's binding sites or used Z-score statistics to search for the
      overrepresented nucleotides of a certain size. We argue that most of these
      methods are not well-suited for RNA motif identification, as they are unable to
      incorporate the RNA structural context of protein-RNA interactions, which may
      affect to binding specificity. Here, we describe a novel model-based approach-
      RNAMotifModeler to identify the consensus of protein-RNA binding regions by
      integrating sequence features and RNA secondary structures. RESULTS: As an
      example, we implemented RNAMotifModeler on SRSF1 (SF2/ASF) CLIP-seq data. The
      sequence-structural consensus we identified is a purine-rich octamer 'AGAAGAAG'
      in a highly single-stranded RNA context. The unpaired probabilities, the
      probabilities of not forming pairs, are significantly higher than negative
      controls and the flanking sequence surrounding the binding site, indicating that
      SRSF1 proteins tend to bind on single-stranded RNA. Further statistical
      evaluations revealed that the second and fifth bases of SRSF1octamer motif have
      much stronger sequence specificities, but weaker single-strandedness, while the
      third, fourth, sixth and seventh bases are far more likely to be single-stranded,
      but have more degenerate sequence specificities. Therefore, we hypothesize that
      nucleotide specificity and secondary structure play complementary roles during
      binding site recognition by SRSF1. CONCLUSION: In this study, we presented a
      computational model to predict the sequence consensus and optimal RNA secondary
      structure for protein-RNA binding regions. The successful implementation on SRSF1
      CLIP-seq data demonstrates great potential to improve our understanding on the
      binding specificity of RNA binding proteins.

PMID- 22369184
TI  - Differing clinical features in Aboriginal vs. non-Aboriginal children presenting
      with type 2 diabetes.
AB  - OBJECTIVES: Childhood type 2 diabetes (T2D) is increasing and may present
      differently across various populations. This study compares clinical features of
      T2D at diagnosis in Aboriginal children with Caucasian children and children from
      other high-risk ethnic groups. PATIENTS AND METHODS: This retrospective
      observational study used data from a Canadian surveillance study where newly
      diagnosed cases of childhood T2D were reported (n = 227). Using descriptive
      statistics, clinical features at diagnosis of T2D were compared across different
      ethnic groups including Aboriginal (n = 100), Caucasian (n = 57), and other high
      risk ethnic groups (n = 64). Comparisons were made between Aboriginal children
      living in central Canada (Manitoba/northwestern Ontario) (n = 74) and Aboriginal
      children from other regions of Canada (n = 26). RESULTS: Aboriginal children were
      younger, less obese, and less likely to have polycystic ovarian syndrome and
      dyslipidemia when compared to Caucasian children and children from other high
      risk ethnic groups (p < 0.05). Aboriginal children from central Canada vs. those
      from other regions of Canada did not differ in age, body mass index z-score,
      family history of T2D, or presence of acanthosis nigricans. Those from central
      Canada had lower hemoglobin A1c levels (p < 0.05) and were less likely to have
      dyslipidemia than Aboriginal children from other regions (p < 0.05). CONCLUSIONS:
      Clinical features and rates of comorbidity in children with newly diagnosed T2D
      differ across various populations (Caucasian, Aboriginal, and children who belong
      to other high-risk ethnic groups) and across distinct Aboriginal populations
      (those living in central Canada vs. those living in other regions of Canada).
      Future research should determine specific genetic and environmental factors that
      contribute to these differences.

PMID- 22369185
TI  - High frequency of false positive IgM immunoblots for Borrelia burgdorferi in
      clinical practice.
AB  - Although it is known that two-tier serologic testing for Lyme disease may be
      associated with false positive results on the IgM immunoblot, this problem has
      never been systematically studied in the clinical practice setting. In a
      retrospective investigation of patients referred to the private adult practice of
      an Infectious Diseases physician for possible for Lyme disease, 50 of 182
      patients (27.5%, 95% CI: 21.1-34.6) were found to have a false positive IgM
      immunoblot. 78.0% of these patients had received unnecessary antibiotic therapy.
      False positive results were not restricted to any single commercial laboratory.
      Research on alternative testing strategies that eliminate the IgM immunoblot
      entirely is warranted.

PMID- 22369186
TI  - FReDoWS: a method to automate molecular docking simulations with explicit
      receptor flexibility and snapshots selection.
AB  - BACKGROUND: In silico molecular docking is an essential step in modern drug
      discovery when driven by a well defined macromolecular target. Hence, the process
      is called structure-based or rational drug design (RDD). In the docking step of
      RDD the macromolecule or receptor is usually considered a rigid body. However, we
      know from biology that macromolecules such as enzymes and membrane receptors are
      inherently flexible. Accounting for this flexibility in molecular docking
      experiments is not trivial. One possibility, which we call a fully-flexible
      receptor model, is to use a molecular dynamics simulation trajectory of the
      receptor to simulate its explicit flexibility. To benefit from this concept,
      which has been known since 2000, it is essential to develop and improve new tools
      that enable molecular docking simulations of fully-flexible receptor models.
      RESULTS: We have developed a Flexible-Receptor Docking Workflow System (FReDoWS)
      to automate molecular docking simulations using a fully-flexible receptor model.
      In addition, it includes a snapshot selection feature to facilitate acceleration
      the virtual screening of ligands for well defined disease targets. FReDoWS
      usefulness is demonstrated by investigating the docking of four different ligands
      to flexible models of Mycobacterium tuberculosis' wild type InhA enzyme and
      mutants I21V and I16T. We find that all four ligands bind effectively to this
      receptor as expected from the literature on similar, but wet experiments.
      CONCLUSIONS: A work that would usually need the manual execution of many computer
      programs, and the manipulation of thousands of files, was efficiently and
      automatically performed by FReDoWS. Its friendly interface allows the user to
      change the docking and execution parameters. Besides, the snapshot selection
      feature allowed the acceleration of docking simulations. We expect FReDoWS to
      help us explore more of the role flexibility plays in receptor-ligand
      interactions. FReDoWS can be made available upon request to the authors.

PMID- 22369187
TI  - Buprenorphine 5, 10 and 20 MUg/h transdermal patch: a guide to its use in chronic
      non-malignant pain.
AB  - Buprenorphine lower-dose (5, 10 and 20 MUg/h) transdermal patches, which are
      administered once every 7 days, are indicated in the management of chronic non
      malignant pain. This review focuses on the labelling of this formulation
      (BuTrans(r)) in the EU. The analgesic efficacy of transdermal buprenorphine in
      patients with osteoarthritis of the hip and/or knee has been demonstrated to be
      equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol
      and generally superior to a matching transdermal placebo patch. When used
      together with regularly scheduled oral paracetamol (acetaminophen), transdermal
      buprenorphine was noninferior to codeine plus paracetamol. Transdermal
      buprenorphine has also shown analgesic efficacy in patients with chronic non
      malignant pain of various causes.

PMID- 22369188
TI  - Exploiting evolution to treat drug resistance: combination therapy and the double
      bind.
AB  - Although many anticancer therapies are successful in killing a large percentage
      of tumor cells when initially administered, the evolutionary dynamics
      underpinning tumor progression mean that, often, resistance is an inevitable
      outcome. Research in the field of ecology suggests that an evolutionary double
      bind could be an effective way to treat tumors. In an evolutionary double bind
      two therapies are used in combination such that evolving resistance to one leaves
      individuals more susceptible to the other. In this paper we present a general
      evolutionary game theory framework of a double bind to study the effect that such
      an approach would have in cancer. Furthermore we use this mathematical framework
      to understand recent experimental results that suggest a synergistic effect
      between a p53 cancer vaccine and chemotherapy. Our model recapitulates the latest
      experimental data and provides an explanation for its effectiveness based on the
      commensalistic relationship between the tumor phenotypes.

PMID- 22369189
TI  - Characterization of the genetic basis for autosomal recessive hereditary
      nephropathy in the English Springer Spaniel.
AB  - BACKGROUND: Autosomal recessive hereditary nephropathy (ARHN) was diagnosed in 2
      English Springer Spaniels (ESS), a breed not previously reported to be affected
      by hereditary nephropathy (HN). OBJECTIVE: To identify and characterize the
      genetic cause of ARHN in ESS. ANIMALS: Sixty-three ESS (2 with ARHN, 2 obligate
      carriers, and 59 others), 2 mixed-breed dogs with X-linked HN, and 2 English
      Cocker Spaniels (ECS) with ARHN were included. METHODS: ARHN was diagnosed based
      on transmission electron microscopy and immunostaining of kidney. DNA from
      affected dogs was screened for the mutation known to cause ARHN in ECS.
      Quantities of COL4A3, COL4A4, and COL4A5 mRNA transcripts in renal cortex were
      determined using quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR) for ARHN-affected dogs and 7 other dogs. The coding regions of COL4A3
      and COL4A4 were sequenced for the 2 ARHN-affected ESS and an unaffected dog. Exon
      30 of COL4A4 was sequenced for all 63 ESS. RESULTS: qRT-PCR indicated a
      significant reduction in transcript levels of both COL4A3 and COL4A4 mRNA in the
      kidney of ARHN-affected ESS. Sequencing identified a single nucleotide
      substitution in COL4A4 at base 2806 resulting in a premature stop codon. Thirteen
      of 25 related dogs were identified as carriers. CONCLUSIONS AND CLINICAL
      IMPORTANCE: A mutation highly likely to cause ARHN in ESS has been identified.

PMID- 22369190
TI  - Proteomics of muscle-specific beef color stability.
AB  - The objective of the present study was to differentiate the sarcoplasmic proteome
      of color-stable (Longissimus lumborum; LL) and color-labile (Psoas major; PM)
      beef muscles. LL and PM muscles from seven beef carcasses (24 h post-mortem) were
      fabricated into 2.54 cm steaks, aerobically packaged, and assigned to
      refrigerated retail display for 9 days. LL steaks demonstrated greater (P < 0.05)
      color stability and lower (P < 0.05) lipid oxidation than PM steaks. Proteome
      analyses identified 16 differentially abundant proteins in LL and PM, including
      antioxidant proteins and chaperones. Proteins demonstrating positive correlation
      with redness (aldose reductase, creatine kinase, and beta-enolase) and color
      stability (peroxiredoxin-2, peptide methionine sulfoxide reductase, and heat
      shock protein-27 kDa) were overabundant in LL, whereas the protein overabundant
      in PM (mitochondrial aconitase) exhibited negative correlation with redness. The
      color stability of LL could be attributed to the overabundance of antioxidant
      proteins and chaperones, and this finding suggests the necessity of developing
      muscle-specific processing strategies to improve beef color.

PMID- 22369191
TI  - Self-resolving invasive squamous cell carcinoma or giant keratoacanthoma?

PMID- 22369192
TI  - Motivations and experiences of women who accessed "see and treat" cervical cancer
      prevention services in Zambia.
AB  - BACKGROUND: In Zambia, a country with a generalized HIV epidemic, age-adjusted
      cervical cancer incidence is among the highest worldwide. In 2006, the University
      of Alabama at Birmingham-Center for Infectious Disease Research in Zambia and the
      Zambian Ministry of Health launched a visual inspection with acetic acid (VIA) 
      based "see and treat" cervical cancer prevention program in Lusaka. All services
      were integrated within existing government-operated primary health care
      facilities. OBJECTIVE: Study aims were to (i) identify women's motivations for
      cervical screening, (ii) document women's experiences with screening and (iii)
      describe the potentially reciprocal influences between women undergoing cervical
      screening and their social networks. DESIGN AND METHODS: Focus group discussions
      (FGD) and in-depth interviews (IDI) were conducted with women who accepted
      screening and with care providers. Low-level content analysis was performed to
      identify themes evoked by participants. Between September 2009 and July 2010, 60
      women and 21 care providers participated in 8 FGD and 10 IDI. RESULTS: Women
      presented for screening with varying needs and expectations. A majority discussed
      their screening decisions and experiences with members of their social networks.
      Key reinforcing factors and obstacles to VIA screening were identified.
      CONCLUSIONS: Interventions are needed to gain support for the screening process
      from influential family members and peers.

PMID- 22369193
TI  - Alteration of peripheral blood monocyte gene expression in humans following
      diesel exhaust inhalation.
AB  - CONTEXT: Epidemiologic associations between acutely increased cardiorespiratory
      morbidity and mortality and particulate air pollution are well established, but
      the effects of acute pollution exposure on human gene expression changes are not
      well understood. OBJECTIVE: In order to identify potential mechanisms underlying
      epidemiologic associations between air pollution and morbidity, we explored
      changes in gene expression in humans following inhalation of fresh diesel exhaust
      (DE), a model for particulate air pollution. MATERIALS AND METHODS: Fourteen
      ethnically homogeneous (white males), young, healthy subjects underwent 60-min
      inhalation exposures on 2 separate days with clean filtered air (CA) or freshly
      generated and diluted DE at a concentration of 300 MUg/m(3) PM(2.5). Prior to and
      24 h following each session, whole blood was sampled and fractionated for
      peripheral blood mononuclear cell (PBMC) isolation, RNA extraction, and
      generation of cDNA, followed by hybridization with Agilent Whole Human Genome
      (4X44K) arrays. RESULTS: Oxidative stress and the ubiquitin proteasome pathway,
      as well as the coagulation system, were among hypothesized pathways identified by
      analysis of differentially expressed genes. Nine genes from these pathways were
      validated using real-time polymerase chain reaction (PCR) to compare fold change
      in expression between DE exposed and CA days. Quantitative gene fold changes
      generated by real-time PCR were directionally consistent with the fold changes
      from the microarray analysis. DISCUSSION AND CONCLUSION: Changes in gene
      expression connected with key oxidative stress, protein degradation, and
      coagulation pathways are likely to underlie observed physiologic and clinical
      outcomes and suggest specific avenues and sensitive time points for further
      physiologic exploration.

PMID- 22369194
TI  - A lung dosimetry model of vapor uptake and tissue disposition.
AB  - Inhaled vapors may be absorbed at the alveolar-capillary membrane and enter
      arterial blood flow to be carried to other organs of the body. Thus, the
      biological effects of inhaled vapors depend on vapor uptake in the lung and
      distribution to the rest of the body. A mechanistic model of vapor uptake in the
      human lung and surrounding tissues was developed for soluble and reactive vapors
      during a single breath. Lung uptake and tissue disposition of inhaled
      formaldehyde, acrolein, and acetaldehyde were simulated for different
      solubilities and reactivities. Formaldehyde, a highly reactive and soluble vapor,
      was estimated to be taken up by the tissues in the upper tracheobronchial airways
      with shallow penetration into the lung. Vapors with moderate solubility such as
      acrolein and acetaldehyde were estimated to penetrate deeper into the lung,
      reaching the alveolar region where absorbed vapors had a much higher probability
      of passing through the thin alveolar-capillary membrane to reach the blood. For
      all vapors, tissue concentration reached its maximum at the end of inhalation at
      the air-tissue interface. The depth of peak concentration moved within the tissue
      layer due to vapor desorption during exhalation. The proposed vapor uptake model
      offers a mechanistic approach for calculations of lung vapor uptake, air:tissue
      flux, and tissue concentration profiles within the respiratory tract that can be
      correlated to local biological response in the lung. In addition, the uptake
      model provides the necessary input for pharmacokinetic models of inhaled
      chemicals in the body, thus reducing the need for estimating requisite
      parameters.

PMID- 22369195
TI  - Swedish forensic data 1992-2009 suggest hydrogen cyanide as an important cause of
      death in fire victims.
AB  - Between 60 and 80% of all deaths related to fire are attributed to toxic fumes.
      Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen
      cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire
      related fatalities is unknown. The aim of the study was to investigate the impact
      of HCN in relation to CO as a cause of death in fire victims. Data on
      carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the
      period 1992-2009 were collected from two Swedish nationwide forensic databases
      (ToxBase and RattsBase). The databases contain data on COHb and/or cyanide from
      2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric
      statistical tests were used. Seventeen percent of the victims had lethal or life
      threatening blood cyanide levels (>1 ug/g) and 32% had lethal COHb levels (>50%
      COHb). Over 31% had cyanide levels above 0.5 ug/g, an indication of significant
      HCN exposure. The percentages may be underestimates, as cyanide is quickly
      eliminated in blood also after death. Our results support the notion that HCN
      contributes more to the cause of death among fire victims than previously
      thought.

PMID- 22369196
TI  - A review of community engagement in cancer control studies among Indigenous
      people of Australia, New Zealand, Canada and the USA.
AB  - This review aimed to address studies of cancer control in Indigenous populations,
      with a focus on: (1) the nature and extent of community engagement; and (2) the
      extent to which community engagement has facilitated successful outcomes.
      Articles addressing Indigenous cancer control using some degree of community
      engagement were identified by a search of the following electronic databases:
      MEDLINE (via Ovid and Pubmed), psycINFO, CINAHL and Google Scholar. Relevant
      studies were scored and analysed according to Green et al.'s guidelines for
      participatory research. Studies often engaged the community only minimally. Where
      studies resulted in successful outcomes, they tended to have included Indigenous
      community members in genuine research roles, from planning, to implementation, to
      presentation of results at conferences. Studies with positive health outcomes
      were often initiated by a combination of academic researchers and community
      members or organisations. This narrative review highlighted significant scope for
      improvement in community-based studies addressing Indigenous cancer control.
      Increased attention to the philosophical underpinnings of community engagement is
      required to ensure that the benefits of this approach are translated to achieve
      improved cancer control outcomes. An increased awareness of the benefits of
      community engagement may prove effective in conducting cancer control research
      that leads to improved outcomes in Indigenous communities.

PMID- 22369198
TI  - From bradykinin B2 receptor antagonists to orally active and selective bradykinin
      B1 receptor antagonists.
AB  - The bradykinin (BK) B1 receptor is an attractive target for the treatment of
      chronic pain and inflammation. Starting from a dual B1 and B2 antagonist, novel
      antagonists were designed that display low-nanomolar affinity for human B1
      receptor and selectivity over B2. Initially, potent imidazoline derivatives were
      studied, but these compounds suffered from low bioavailability. This issue could
      be overcome by the use of less basic amino derivatives leading to orally active
      compounds.

PMID- 22369197
TI  - Correction of aberrant NADPH oxidase activity in blood-derived mononuclear cells
      from type II diabetes mellitus patients by a naturally fermented papaya
      preparation.
AB  - Supplementation of standardized fermented papaya preparation (FPP) to adult
      diabetic mice improves dermal wound healing outcomes. Peripheral blood
      mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a
      compromised respiratory burst activity resulting in increased risk of infections
      for the diabetic patients. AIMS: The objectives of the current study were to
      determine the effect of FPP supplementation on human diabetic PBMC respiratory
      burst activity and to understand underlying mechanisms of such action of FPP.
      RESULTS: When stimulated with phorbol 12-myristate 13-acetate, the production of
      reactive oxygen species by T2DM PBMC was markedly compromised compared to that of
      the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst
      outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of
      the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA
      expression of Rac2 was potently upregulated after FPP supplemention. The proximal
      human Rac2 gene promoter is G-C rich and contains consensus binding sites for Sp1
      and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity,
      the Sp1 DNA binding activity was significantly upregulated in PBMC after
      treatment of the cells with FPP. INNOVATION: This work provided first evidence
      that compromised respiratory burst performance of T2DM PBMC may be corrected by a
      nutritional supplement. CONCLUSION: FPP can correct respiratory burst performance
      of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP
      supplementation in diabetic patients are warranted.

PMID- 22369199
TI  - Attentional mechanisms in learned predictiveness.
AB  - Cues that reliably predict an outcome in an initial phase of training (Phase 1)
      are learned faster in a second phase of training (Phase 2) than cues that were
      unreliable in Phase 1. This result is observed despite objectively equal
      relationships between the cues and the outcomes in Phase 2, and consequently
      constitutes a nonnormative bias in learning. The present experiments sought to
      confirm that this learned predictiveness effect is the product of attentional
      processes (Experiment 1), and to test further whether these processes are under
      voluntary control or are automatic in nature (Experiment 2). In addition to the
      usual outcome prediction measure, eye-gaze behavior was also monitored. The
      results indicated an important role for top-down strategic attentional processes
      in the learned predictiveness task. In contrast, no evidence for an automatic
      attentional bias was found.

PMID- 22369200
TI  - Latent spatial learning in an environment with a distinctive shape.
AB  - Four experiments were conducted with rats in order to determine whether being
      placed on a platform in one corner of a rectangular swimming pool results in
      latent spatial learning. Rats in Experiments 1-3 received four trials a day of
      being placed on the platform. During a subsequent test trial, in which they were
      released into the pool without the platform, the rats exhibited a preference for
      swimming in the correct corners of the pool (those with the same geometric
      properties as the corner containing the platform during training), than the two
      remaining, incorrect corners. This effect was seen when the interval between the
      final placement trial and the test trial was as much as 24 hr (Experiment 2) and
      after varying numbers of sessions of placement training (Experiment 3).
      Experiment 4 revealed that when the test took place in a kite-shaped arena, after
      placement training in a rectangle, a stronger preference was shown for the corner
      that was geometrically equivalent to the correct rather than the incorrect
      corners in the rectangle. The placement treatment is said to result in latent
      spatial learning based on the development of S-S associations.

PMID- 22369201
TI  - Liverome: a curated database of liver cancer-related gene signatures with self
      contained context information.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer
      worldwide. A number of molecular profiling studies have investigated the changes
      in gene and protein expression that are associated with various
      clinicopathological characteristics of HCC and generated a wealth of scattered
      information, usually in the form of gene signature tables. A database of the
      published HCC gene signatures would be useful to liver cancer researchers seeking
      to retrieve existing differential expression information on a candidate gene and
      to make comparisons between signatures for prioritization of common genes. A
      challenge in constructing such database is that a direct import of the signatures
      as appeared in articles would lead to a loss or ambiguity of their context
      information that is essential for a correct biological interpretation of a gene's
      expression change. This challenge arises because designation of compared sample
      groups is most often abbreviated, ad hoc, or even missing from published
      signature tables. Without manual curation, the context information becomes lost,
      leading to uninformative database contents. Although several databases of gene
      signatures are available, none of them contains informative form of signatures
      nor shows comprehensive coverage on liver cancer. Thus we constructed Liverome, a
      curated database of liver cancer-related gene signatures with self-contained
      context information. DESCRIPTION: Liverome's data coverage is more than three
      times larger than any other signature database, consisting of 143 signatures
      taken from 98 HCC studies, mostly microarray and proteome, and involving 6,927
      genes. The signatures were post-processed into an informative and uniform
      representation and annotated with an itemized summary so that all context
      information is unambiguously self-contained within the database. The signatures
      were further informatively named and meaningfully organized according to ten
      functional categories for guided browsing. Its web interface enables a
      straightforward retrieval of known differential expression information on a query
      gene and a comparison of signatures to prioritize common genes. The utility of
      Liverome-collected data is shown by case studies in which useful biological
      insights on HCC are produced. CONCLUSION: Liverome database provides a
      comprehensive collection of well-curated HCC gene signatures and straightforward
      interfaces for gene search and signature comparison as well. Liverome is
      available at http://liverome.kobic.re.kr.

PMID- 22369203
TI  - High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory
      relation in Human, Mouse, Rat, budding Yeast and E. coli.
AB  - BACKGROUND: The phylogenetic profile is widely used to characterize functional
      linkage and conservation between proteins without amino acid sequence similarity.
      To survey the conservative regulatory properties of rate-limiting enzymes (RLEs)
      in metabolic inhibitory network across different species, we define the enzyme
      inhibiting pair as: where the first enzyme in a pair is the inhibitor provider
      and the second is the target of the inhibitor. Phylogenetic profiles of enzymes
      in the inhibiting pairs are further generated to measure the functional linkage
      of these enzymes during evolutionary history. RESULTS: We find that the RLEs
      generate, on average, over half of all in vivo inhibitors in each surveyed model
      organism. And these inhibitors inhibit on average over 85% targets in metabolic
      inhibitory network and cover the majority of targets of cross-pathway inhibiting
      relations. Furthermore, we demonstrate that the phylogenetic profiles of the
      enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often
      show higher similarities than those in common inhibiting enzyme pairs. In
      addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP
      instead of AMP in conservative inhibitory networks. CONCLUSIONS: Combined with
      the conservative roles of RLEs in their efficiency in sensing metabolic signals
      and transmitting regulatory signals to the rest of the metabolic system, the RLEs
      may be important molecules in balancing energy homeostasis via maintaining the
      ratio of ATP to ADP in living cells. Furthermore, our results indicate that
      similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs
      are not only correlated with enzyme topological importance, but also related with
      roles of the enzymes in metabolic inhibitory network.

PMID- 22369204
TI  - A comparative study of efficacy and outcomes of large loop excision of the
      transformation zone procedure performed under general anaesthesia versus local
      anaesthesia.
AB  - BACKGROUND: Although Australian National Health and Medical Research Council
      (NHMRC) guidelines do not specify targets for mode of anaesthesia for large loop
      excision of the transformation zone (LLETZ) procedures, UK NHS Cervical Screening
      Programme (NHSCSP) guidelines recommend that >80% of LLETZ procedures be
      performed under local anaesthesia. There is a paucity of clinical data regarding
      both the proportion of women receiving general anaesthesia for treatment, factors
      underpinning this choice and the impact of mode of anaesthesia on treatment
      outcomes. AIMS: To identify the proportion of women who have a LLETZ under
      general anaesthesia and to establish the impact of mode of anaesthesia on
      outcomes including treatment efficacy, overtreatment (negative histology), short
      term morbidity and attendance for follow-up. METHODS: Single-centre retrospective
      analysis of all women treated with LLETZ for suspected cervical dysplasia between
      1, May 2005 and 1, May 2009. RESULTS: Thirty-three percent of a total 465 LLETZ
      procedures were carried out under general anaesthesia, although the reason for
      anaesthesia choice was not recorded in 52% of cases. There were no significant
      differences in the primary outcomes of unclear LLETZ margins or negative LLETZ
      histology, or in the secondary outcomes of depth and surface area of LLETZ
      specimen, short-term morbidity or rates of incomplete follow-up. CONCLUSIONS:
      Although reasons underpinning selection of anaesthesia mode remain elusive, at
      this centre, outcomes following LLETZ procedure for the management of suspected
      cervical dysplasia are not affected by the mode of anaesthesia used.

PMID- 22369205
TI  - Radiosensitization by the novel DNA intercalating agent vosaroxin.
AB  - PURPOSE: Vosaroxin is a first in class naphthyridine analog structurally related
      to quinolone antibacterials, that intercalates DNA and inhibits topoisomerase II.
      Vosaroxin is not a P-glycoprotein receptor substrate and its activity is
      independent of p53, thus evading common drug resistance mechanisms. To evaluate
      vosaroxin as a clinically applicable radiation sensitizer, we investigated its
      effects on tumor cell radiosensitivity in vitro and in vivo. METHODS: Vosaroxin's
      effect on post-irradiation sensitivity of U251, DU145, and MiaPaca-2 cells was
      assessed by clonogenic assay. Subsequent mechanistic and in vivo studies were
      performed with U251 cells. Cell cycle distribution and G2 checkpoint integrity
      was analyzed by flow cytometry. DNA damage and repair was evaluated by a high
      throughput gamma-H2AX assay. Apoptosis was assessed by flow cytometry. Mitotic
      catastrophe was assessed by microscopic evidence of fragmented nuclei by
      immunofluorescence. In vivo radiosensitization was measured by subcutaneous tumor
      growth delay. RESULTS: 50-100 nmol/L treatment with vosaroxin resulted in
      radiosensitization of all 3 cell lines tested with a dose enhancement factor of
      1.20 to 1.51 measured at a surviving fraction of 0.1. The maximal dose
      enhancement was seen in U251 cells treated with 75 nmol/L vosaroxin (DEF 1.51).
      Vosaroxin exposure did not change cell cycle distribution prior to irradiation
      nor alter G2 checkpoint integrity after irradiation. No difference was seen in
      the apoptotic fraction regardless of drug or radiation treatment. The number of
      cells in mitotic catastrophe was significantly greater in irradiated cells
      treated with vosaroxin than cells receiving radiation only at 72 hr (p = 0.009).
      Vosaroxin alone did not significantly increase mitotic catastrophe over control
      (p = 0.53). Cells treated with vosaroxin and radiation maintained significantly
      higher gamma-H2AX levels than cells treated with vehicle control (p = 0.014),
      vosaroxin (p = 0.042), or radiation alone (p = 0.039) after 24 hr. In vivo tumor
      growth delay was 1.5 days for vosaroxin alone (IV 10 mg/kg), 1.0 days for
      radiation (3 Gy) alone, and 8.6 days for the group treated with vosaroxin 4 hours
      prior to radiation. CONCLUSIONS: Vosaroxin enhanced tumor cell radiosensitivity
      in vitro and in vivo. The mechanism appears to be related to inhibition of DNA
      repair and increased mitotic catastrophe.

PMID- 22369206
TI  - An independent effect of parental lipids on the offspring lipid levels in a
      cohort of adolescents with type 1 diabetes.
AB  - BACKGROUND: Genetic factors modulate lipid levels and an intrafamilial
      aggregation of abnormal lipid profiles has been reported in the general
      population. As dyslipidemia is common among people with diabetes and has been
      related to diabetic nephropathy, we investigated whether parental lipid levels
      were related to lipids and albumin excretion in young offspring with childhood
      onset type 1 diabetes (T1D). METHODS: Non-fasting blood samples were collected
      from 895 offspring, 808 mothers and 582 fathers. Total cholesterol (TC),
      triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C) and non-HDL-C were measured. Three early morning
      urinary albumin-creatinine ratios (ACR), hemoglobin A1C (HbA1c) and
      anthropometric parameters were also assessed. RESULTS: The offspring's mean age
      (+/-SD) was 14.5 +/- 2.2 yr, mean diabetes duration 5.5 +/- 3.7 yr; the fathers'
      age was 45.7 +/- 6.1 yr and the mothers' age was 42.8 +/- 5.5 yr. After adjusting
      for the offspring age, gender, body mass index, HbA1c, maternal (TC: beta =
      0.242; TG: beta = 0.152; HDL-C: beta = 0.285; LDL-C: beta = 0.278; non-HDL-C:
      beta = 0.253; all p < 0.001) and paternal lipid levels (TC: beta = 0.188; TG:
      beta = 0.108; HDL-C: beta = 0.253; LDL-C: beta = 0.187; non-HDL-C: beta = 0.173;
      all p < 0.001) were significantly associated with the offspring's lipid
      parameters. In contrast, no significant association was found between parental
      lipid levels and the offspring's ACR. CONCLUSIONS: In the present study, parental
      lipid levels were independently associated with the same traits in the offspring,
      suggesting a role of genetic influences and/or shared environmental factors in
      modulating the metabolic profile of adolescents with T1D. In contrast, there was
      no significant association between parental lipid levels and the offspring's
      albumin excretion.

PMID- 22369207
TI  - Prolonged and mixed non-O157 Escherichia coli infection in an Australian
      household.
AB  - An Australian family was identified through a Public Health follow up on a Shiga
      toxigenic Escherichia coli (STEC) positive bloody diarrhoea case, with three of
      the four family members experiencing either symptomatic or asymptomatic STEC
      shedding. Bacterial isolates were submitted to stx sequence sub-typing, multi
      locus variable number tandem repeat analysis (MLVA), multi-locus sequence typing
      (MLST) and binary typing. The analysis revealed that there were multiple strains
      of STEC being shed by the family members, with similar virulence gene profiles
      and the same serogroup but differing in their MLVA and MLST profiles. This study
      illustrates the potentially complicated nature of non-O157 STEC infections and
      the importance of molecular epidemiology in understanding disease clusters.

PMID- 22369209
TI  - PDCD6 is an independent predictor of progression free survival in epithelial
      ovarian cancer.
AB  - BACKGROUND: Programmed cell death 6 (PDCD6) beside its known proapoptotic
      functions may be a player in survival pathways in cancer. The purpose of this
      study is to further explore the roles of PDCD6 in epithelial ovarian cancer.
      METHODS: Lentiviral vector with shRNA for PDCD6 was used to investigate the
      effects of PDCD6 knockdown on cell growth, cell cycle, apoptosis and motility in
      ovarian cancer cells. Two hundred twelve epithelial ovarian cancer tissues were
      analyzed for mRNA expression of PDCD6 using RT-PCR. Associations of its
      expression with clinical pathological factors, progression free and overall
      survival were evaluated. RESULTS: PDCD6 is highly expressed in metastatic ovarian
      cancer cells and positively regulates cell migration and invasion. Significantly,
      the level of PDCD6 expression in epithelial ovarian cancer correlates with
      clinical progression. Patients with medium or high levels of PDCD6 mRNA were at
      higher risk for disease progression, compared to those with low levels (HR, 1.29;
      P = 0.024 for medium levels; and HR, 1.57; P = 0.045 for high levels) after
      adjusting for age, disease stage, tumor grade, histologic type and residual tumor
      size. Kaplan-Meier survival analysis demonstrated similar results. However, no
      association was found between PDCD6 expression and overall survival. CONCLUSIONS:
      PDCD6 seems to play an important role in ovarian cancer progression and it may be
      an independent predictor of progression free survival in epithelial ovarian
      cancer. Further studies are needed to more completely elucidate the molecular
      mechanisms of PDCD6 involve in ovarian cancer progression.

PMID- 22369210
TI  - Spectroscopic study on imidazolium-based ionic liquids: effect of alkyl chain
      length and anion.
AB  - Room temperature ionic liquids are currently used as functional materials in
      several application and their optical investigation can provide a better
      understanding of their physical and chemical behavior. Absorption and emission
      properties of imidazolium-based ILs have been attributed to the imidazolium
      moiety and related to the presence of energetically different aggregates. Here,
      time-integrated and time-resolved investigation has been carried out on 1-alkyl-3
      methylimidazolium tetrafluoroborate and hexafluorophosphate ionic liquids with
      different chain lengths in order to probe the occurrence of energy transfer
      processes, and hence to disclose the presence of various states with different
      energy. Such a study contributes to provide relevant insight on the effect of
      alkyl chain and anion type on the emission characteristics, and, hence, on the
      presence of associated structures.

PMID- 22369208
TI  - Protease-associated cellular networks in malaria parasite Plasmodium falciparum.
AB  - BACKGROUND: Malaria continues to be one of the most severe global infectious
      diseases, responsible for 1-2 million deaths yearly. The rapid evolution and
      spread of drug resistance in parasites has led to an urgent need for the
      development of novel antimalarial targets. Proteases are a group of enzymes that
      play essential roles in parasite growth and invasion. The possibility of
      designing specific inhibitors for proteases makes them promising drug targets.
      Previously, combining a comparative genomics approach and a machine learning
      approach, we identified the complement of proteases (degradome) in the malaria
      parasite Plasmodium falciparum and its sibling species 123, providing a catalog
      of targets for functional characterization and rational inhibitor design. Network
      analysis represents another route to revealing the role of proteins in the
      biology of parasites and we use this approach here to expand our understanding of
      the systems involving the proteases of P. falciparum. RESULTS: We investigated
      the roles of proteases in the parasite life cycle by constructing a network using
      protein-protein association data from the STRING database 4, and analyzing these
      data, in conjunction with the data from protein-protein interaction assays using
      the yeast 2-hybrid (Y2H) system 5, blood stage microarray experiments 678,
      proteomics 9101112, literature text mining, and sequence homology analysis.
      Seventy-seven (77) out of 124 predicted proteases were associated with at least
      one other protein, constituting 2,431 protein-protein interactions (PPIs). These
      proteases appear to play diverse roles in metabolism, cell cycle regulation,
      invasion and infection. Their degrees of connectivity (i.e., connections to other
      proteins), range from one to 143. The largest protease-associated sub-network is
      the ubiquitin-proteasome system which is crucial for protein recycling and stress
      response. Proteases are also implicated in heat shock response, signal peptide
      processing, cell cycle progression, transcriptional regulation, and signal
      transduction networks. CONCLUSIONS: Our network analysis of proteases from P.
      falciparum uses a so-called guilt-by-association approach to extract sets of
      proteins from the proteome that are candidates for further study. Novel protease
      targets and previously unrecognized members of the protease-associated sub
      systems provide new insights into the mechanisms underlying parasitism,
      pathogenesis and virulence.

PMID- 22369211
TI  - Diffuse reflectance infrared Fourier transform study of NO(x) adsorption on CGO10
      impregnated with K2O or BaO.
AB  - In the present work diffuse reflectance infrared Fourier transform (DRIFT)
      spectroscopy is applied to study the adsorption of NO(x) at 300-500  degrees C in
      different atmospheres on gadolinium-doped ceria (CGO), an important material in
      electrodes investigated for electrochemical NO(x) removal. Furthermore, the
      effect on the NO(x) adsorption when adding K(2)O or BaO to the CGO is
      investigated. The DRIFT study shows mainly the presence of nitrate species at 500
      degrees C, whereas at lower temperature a diversity of adsorbed NO(x) species
      exists on the CGO. The presence of O(2) is shown to have a strong effect on the
      adsorption of NO, but no effect on the adsorption of NO(2). Addition of K(2)O and
      BaO dramatically affects the NO(x) adsorption and the results also show that the
      adsorbed NO(x) species are mobile and capable of changing adsorption state in the
      investigated temperature range.

PMID- 22369213
TI  - Effect of the explicit flexibility of the InhA enzyme from Mycobacterium
      tuberculosis in molecular docking simulations.
AB  - BACKGROUND: Protein/receptor explicit flexibility has recently become an
      important feature of molecular docking simulations. Taking the flexibility into
      account brings the docking simulation closer to the receptors' real behaviour in
      its natural environment. Several approaches have been developed to address this
      problem. Among them, modelling the full flexibility as an ensemble of snapshots
      derived from a molecular dynamics simulation (MD) of the receptor has proved very
      promising. Despite its potential, however, only a few studies have employed this
      method to probe its effect in molecular docking simulations. We hereby use
      ensembles of snapshots obtained from three different MD simulations of the InhA
      enzyme from M. tuberculosis (Mtb), the wild-type (InhA_wt), InhA_I16T, and
      InhA_I21V mutants to model their explicit flexibility, and to systematically
      explore their effect in docking simulations with three different InhA inhibitors,
      namely, ethionamide (ETH), triclosan (TCL), and pentacyano(isoniazid)ferrate(II)
      (PIF). RESULTS: The use of fully-flexible receptor (FFR) models of InhA_wt,
      InhA_I16T, and InhA_I21V mutants in docking simulation with the inhibitors ETH,
      TCL, and PIF revealed significant differences in the way they interact as
      compared to the rigid, InhA crystal structure (PDB ID: 1ENY). In the latter, only
      up to five receptor residues interact with the three different ligands.
      Conversely, in the FFR models this number grows up to an astonishing 80 different
      residues. The comparison between the rigid crystal structure and the FFR models
      showed that the inclusion of explicit flexibility, despite the limitations of the
      FFR models employed in this study, accounts in a substantial manner to the
      induced fit expected when a protein/receptor and ligand approach each other to
      interact in the most favourable manner. CONCLUSIONS: Protein/receptor explicit
      flexibility, or FFR models, represented as an ensemble of MD simulation
      snapshots, can lead to a more realistic representation of the induced fit effect
      expected in the encounter and proper docking of receptors to ligands. The FFR
      models of InhA explicitly characterizes the overall movements of the amino acid
      residues in helices, strands, loops, and turns, allowing the ligand to properly
      accommodate itself in the receptor's binding site. Utilization of the intrinsic
      flexibility of Mtb's InhA enzyme and its mutants in virtual screening via
      molecular docking simulation may provide a novel platform to guide the rational
      or dynamical-structure-based drug design of novel inhibitors for Mtb's InhA. We
      have produced a short video sequence of each ligand (ETH, TCL and PIF) docked to
      the FFR models of InhA_wt. These videos are available at
      http://www.inf.pucrs.br/~osmarns/LABIO/Videos_Cohen_et_al_19_07_2011.htm.

PMID- 22369214
TI  - Construction and analysis of a plant non-specific lipid transfer protein database
      (nsLTPDB).
AB  - BACKGROUND: Plant non-specific lipid transfer proteins (nsLTPs) are small and
      basic proteins. Recently, nsLTPs have been reported involved in many
      physiological functions such as mediating phospholipid transfer, participating in
      plant defence activity against bacterial and fungal pathogens, and enhancing cell
      wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is
      still unclear, and comprehensive information of nsLTPs is difficult to obtain.
      METHODS: In this study, we identified 595 nsLTPs from 121 different species and
      constructed an nsLTPs database--nsLTPDB--which comprises the sequence
      information, structures, relevant literatures, and biological data of all plant
      nsLTPs http://nsltpdb.life.nthu.edu.tw/. RESULTS: Meanwhile, bioinformatics and
      statistics methods were implemented to develop a classification method for nsLTPs
      based on the patterns of the eight highly-conserved cysteine residues, and to
      suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern
      of Type I is C X2 V X5-7 C [V, L, I] * Y [L, A, V] X8-13 CC * G X12 D * [Q, K, R]
      X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T]
      X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] * [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2
      C. Moreover, we referred the Prosite-styled patterns to the experimental
      mutagenesis data that previously established by our group, and found that the
      residues with higher conservation played an important role in the structural
      stability or lipid binding ability of nsLTPs. CONCLUSIONS: Taken together, this
      research has suggested potential residues that might be essential to modulate the
      structural and functional properties of plant nsLTPs. Finally, we proposed some
      biologically important sites of the nsLTPs, which are described by using a new
      Prosite-styled pattern that we defined.

PMID- 22369215
TI  - Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma.
AB  - BACKGROUND: ABT-751 is a novel orally available antimitotic agent that targets
      microtubule polymerization. This mechanism may suggest potential activity in
      canine lymphoma. OBJECTIVE: Determine a maximum tolerated dose for ABT-751, and
      assess long-term tolerability and activity in canine lymphoma. ANIMALS: Thirty
      dogs with newly diagnosed (n = 19) or relapsed (n = 11) non-Hodgkin's lymphoma.
      METHODS: Dogs (n = 11) were enrolled in a rapid dose escalation study to define
      the maximum tolerated dose. Upon definition of a maximally tolerated dose, a
      cohort expansion of 19 dogs allowed verification of long-term tolerability and
      assessment of activity. Study endpoints in the cohort expansion included chronic
      tolerability, response rate, response duration, and time to progression.
      Additional endpoints included serum pharmacokinetics, lymph node drug
      concentrations, and changes in circulating endothelial cells. RESULTS: The
      maximum tolerated dose of ABT-751 was 350 mg/m(2) PO q24h. Dose-limiting
      toxicities included vomiting and diarrhea, which resolved with a schedule
      adjustment to 350 mg/m(2) PO q48h. ABT-751 was consistently detected in lymphoma
      tissue samples from dogs treated at or above the maximum tolerated dose. In the
      cohort expansion, objective responses were seen in 3/15 (20%) dogs with a
      response duration ranging from 21 to 111 days. Decreases in circulating
      endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8
      nonresponding dogs). CONCLUSION: ABT-751 was well tolerated at 350 mg/m(2) PO
      q24h for 7 days and then q48h thereafter. Activity of ABT-751 suggested a
      rationale for additional studies of ABT-751 as part of a combination chemotherapy
      protocol for lymphoma or other canine cancers.

PMID- 22369216
TI  - Hemigossypol, a constituent in developing glanded cottonseed (Gossypium
      hirsutum).
AB  - Gossypol is a dimeric sesquiterpenoid first identified in cottonseed, but found
      in various tissues in the cotton plant including the seed. From its first
      discovery, it was assumed that hemigossypol was the biosynthetic precursor of
      gossypol. Previous studies established that peroxidase (either from horseradish
      or from cottonseed) converts hemigossypol to gossypol. However, hemigossypol has
      never been identified in healthy cottonseed. In a temporal study using HPLC and
      LC-MS, hemigossypol was identified in the developing cotton embryo. It was shown
      to concomitantly accumulate until 40 days postanthesis (dpa) with gossypol and
      with transcripts of delta-cadinene synthase and 8-hydroxy-delta-cadinene
      synthase, genes involved in the biosynthesis of hemigossypol and gossypol. After
      40 dpa, hemigossypol and its biosynthetic gene transcript levels declined,
      whereas the gossypol level remained almost unchanged until the bolls were open.
      These results provide further evidence to support the previous findings that
      establish hemigossypol as the biosynthetic precursor of gossypol.

PMID- 22369217
TI  - The Expectancy Challenge Alcohol Literacy Curriculum (ECALC): a single session
      group intervention to reduce alcohol use.
AB  - The Expectancy Challenge Alcohol Literacy Curriculum (ECALC) is a single session
      group-delivered program designed to modify alcohol expectancy processes and
      reduce alcohol use among children and young adults. The objective of this study
      was to demonstrate the effectiveness of the ECALC in reducing risky alcohol use
      among heavy drinking college men. Four fraternities at a large state university
      were randomly assigned to receive either the single session ECALC or a control
      presentation (2 fraternity houses per condition, n=250). Alcohol expectancies
      were assessed before and immediately after program presentation. Results
      demonstrated significant changes on 5 of the 7 subscales of the Comprehensive
      Effects of Alcohol Scale (CEOA) among students who received the ECALC when
      compared with control participants. Alcohol use data were collected for 4 weeks
      before and 4 weeks after program presentation. Compared with those in the control
      condition, students who received the ECALC demonstrated significant reductions in
      all facets of alcohol use measured, including decreased mean and peak blood
      alcohol content (BAC), decreased mean number of days drinking per week, decreased
      mean drinks per sitting, and decreased number of binge-drinking episodes per
      month. This study represents 2 important advances. First is the significant
      reduction in risky alcohol use produced by a single session group-delivered
      program. The second important advance is the success in changing expectancy
      processes without using impractical elements common in previous expectancy
      challenge methods (e.g., a "barlab" environment and actual alcohol
      administration).

PMID- 22369218
TI  - Characterization of individuals seeking treatment for caffeine dependence.
AB  - Previous investigations have identified individuals who meet criteria for
      Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV
      TR; American Psychiatric Association, 2000) substance dependence as applied to
      caffeine, but there is little research on treatments for caffeine dependence.
      This study aimed to thoroughly characterize individuals who are seeking treatment
      for problematic caffeine use. Ninety-four individuals who identified as being
      psychologically or physically dependent on caffeine, or who had tried
      unsuccessfully to modify caffeine consumption participated in a face-to-face
      diagnostic clinical interview. They also completed measures concerning caffeine
      use and quitting history, reasons for seeking treatment, and standardized self
      report measures of psychological functioning. Caffeine treatment seekers (mean
      age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The
      primary source of caffeine was coffee for 50% of the sample and soft drinks for
      37%. Eighty-eight percent reported prior serious attempts to modify caffeine use
      (mean 2.7 prior attempts), and 43% reported being advised by a medical
      professional to reduce or eliminate caffeine. Ninety-three percent met criteria
      for caffeine dependence when generic DSM-IV-TR substance dependence criteria were
      applied to caffeine use. The most commonly endorsed criteria were withdrawal
      (96%), persistent desire or unsuccessful efforts to control use (89%), and use
      despite knowledge of physical or psychological problems caused by caffeine (87%).
      The most common reasons for wanting to modify caffeine use were health-related
      (59%) and not wanting to be dependent on caffeine (35%). This investigation
      reveals that there are individuals with problematic caffeine use who are seeking
      treatment and suggests that there is a need for effective caffeine dependence
      treatments.

PMID- 22369219
TI  - Alcohol use history and panic-relevant responding among adolescents: a test using
      a voluntary hyperventilation challenge.
AB  - Given the onset of alcohol use, neurological sensitivity, and enhanced panic
      relevant vulnerability, adolescence is a key period in which to study the
      documented linkage between alcohol and panic-related problems. The current study
      was designed to build upon and uniquely extend extant work via (a) utilization of
      well-established experimental psychopathology techniques and (b) evaluation of
      unique associations between alcohol use and panic symptoms after controlling for
      theoretically relevant behavioral, environmental, and individual difference
      variables (i.e., age, gender, negative affectivity, anxiety sensitivity, child
      and parent tobacco use, and parental panic disorder). Participants were 111
      community-recruited adolescents ages 12-17 years (M = 15.76 years; n = 50 girls).
      Youth completed a battery of well-established questionnaires and a voluntary
      hyperventilation challenge, and parents present at the laboratory completed a
      structured clinical interview. Adolescent alcohol use was categorized as Non
      Users, Experimenters, or Users. Panic symptoms were indexed via retrospective
      self-report and adolescents' response to a biological challenge procedure (i.e.,
      voluntary hyperventilation). After controlling for theoretically relevant
      covariates, Users evidenced elevated panic-relevant symptoms and responding
      compared with Non-Users; Experimenters did not differ from Non-Users. Findings
      suggest alcohol use history is uniquely associated with panic symptomatology
      among youth, including "real-time" reactivity elicited by a laboratory challenge.
      Although there is significant work yet to be done, these data advance extant work
      and lay the groundwork for the types of sophisticated designs that will be needed
      to answer the most pressing and complex questions regarding the link between
      alcohol use and panic symptoms among adolescents.

PMID- 22369220
TI  - A comparison of delay discounting among substance users with and without suicide
      attempt history.
AB  - Although substance use disorders are associated with overall increased suicide
      risk, there is considerable variability in suicide risk among substance-dependent
      individuals (SDIs). Impairment in impulse control is common among SDIs, and it
      may contribute to vulnerability to suicidal behavior. The present study examined
      the relation between one specific aspect of impulsivity-delay discounting-and
      suicide attempt history in a sample of SDIs. An interaction was observed between
      suicide attempt history and discounting rates across delayed reward size.
      Specifically, SDIs with no history of attempted suicide, devalued small relative
      to large delayed rewards. In contrast, SDIs with a history of suicide attempts
      appeared comparatively indifferent to delayed reward size, discounting both small
      and large delayed rewards at essentially identical rates. These findings provide
      evidence that, despite the view that SDIs are characterized by marked
      difficulties in impulsivity, significant variability exists within this group in
      delay-discounting tendencies. Furthermore, these differences provide preliminary
      evidence that specific aspects of impulsivity may help to identify those most at
      risk for suicidal behavior in this population. The potential implications of our
      findings for suicide prevention efforts are discussed.

PMID- 22369221
TI  - Symptoms of posttraumatic stress predict craving among alcohol treatment seekers:
      results of a daily monitoring study.
AB  - Alcohol use disorders (AUDs) and Posttraumatic Stress Disorder (PTSD) commonly co
      occur. Craving for alcohol is a common aspect of AUD, with and without PTSD, and
      is one of the key predictors of continued problematic alcohol use among treatment
      seekers. The present study sought to investigate the self-medication hypothesis
      using daily Interactive Voice Response (IVR) reports to examine the relationships
      between PTSD symptomatology and both same-day and next-day alcohol craving.
      Twenty-nine individuals with an AUD (26 of whom screened positive for PTSD)
      entering AUD treatment provided daily IVR data for up to 28 days regarding their
      alcohol use, craving, and 7 symptoms of PTSD. Given the nested nature of daily
      data, generalized estimating equations using a negative binomial distribution and
      a log link function were used to test hypotheses. Results suggest that days with
      greater overall PTSD severity are associated with greater alcohol craving, and
      greater reports of startle and anger/irritability were particularly associated
      with same-day craving. The next-day results suggest that the combination of the 7
      PTSD symptoms did not predict next-day craving. However, greater distress from
      nightmares the previous night, emotional numbing, and hypervigilance predicted
      greater next-day craving, while greater anger/irritability predicted lower next
      day craving. These findings highlight the importance of assessing the
      relationship between specific symptoms of PTSD and alcohol cravings in order to
      increase our understanding of the functional interplay among them for theory
      building. Additionally, clinicians may be better able to refine treatment
      decisions to more efficiently break the cycle between PTSD-related distress and
      AUD symptoms.

PMID- 22369222
TI  - White matter integrity as a link in the association between motivation to abstain
      and treatment outcome in adolescent substance users.
AB  - Readiness to change constitutes an important treatment target. This study
      examined white matter (WM) integrity as a possible link in the pathway between
      motivation to abstain and treatment outcome. Adolescents (age 14-18 years, n =
      32) were recruited from intensive outpatient (IOP) substance use treatment and
      reported on motivation to abstain from alcohol and marijuana shortly after
      treatment admission (i.e., at baseline). Diffusion tensor imaging data were
      collected approximately 7 weeks after starting IOP and were used to quantify WM
      integrity (indexed by fractional anisotropy, FA) using a region of interest (ROI)
      approach. Treatment outcomes were assessed 6 months after baseline. Indirect
      effects analyses tested FA in prefrontal, orbitofrontal, and temporal ROIs as a
      linking variable in the pathway from motivation to abstain to alcohol and
      marijuana outcomes. Bivariate correlations indicated that greater motivation to
      abstain from alcohol was associated with lower FA in prefrontal, orbitofrontal,
      and temporal ROIs and that lower FA in these three ROIs was associated with
      greater 6-month alcohol problem severity. The indirect effect of FA was
      significant for the prefrontal ROI in the pathway from motivation to outcome for
      alcohol. FA values were not associated with motivation to abstain from marijuana
      or marijuana-related outcomes. Results suggest that lower WM integrity,
      particularly in the prefrontal brain region, may help to explain greater alcohol
      problem severity at 6 months despite higher motivation to abstain from alcohol.
      Interventions that aim to enhance WM integrity warrant attention to improve
      adolescent treatment outcomes.

PMID- 22369223
TI  - Delineating potential mechanisms of implicit alcohol cognitions: drinking
      restraint, negative affect, and their relationship with approach alcohol
      associations.
AB  - Problem drinkers may use alcohol to avoid negative mood states and may develop
      implicit cognitive associations between negative emotional states and reinforcing
      properties of drinking. It is paradoxical that attempts to control drinking, such
      as among those high in drinking restraint, may inadvertently increase desire to
      drink and subsequent alcohol consumption, and this may be exaggerated under times
      of emotional distress when urges to drink are high. We examined whether
      individuals who are high on drinking restraint would demonstrate stronger alcohol
      related thoughts elicited by stimuli that represent the desire to use alcohol, in
      response to stronger versus weaker negative mood arousal. Seventy hazardous
      drinkers completed measurements of drinking restraint, alcohol consumption, and
      consequences of use. After being randomized to view negative or positive pictures
      sets, participants completed an Implicit Association Task (IAT) to test
      differences in the strength of the association between desire to approach or
      avoid alcohol or water cues, and then a measurement of subjective craving
      following the IAT. Regression analyses showed that trait restriction not
      temptation was positively related to IAT scores, after controlling for relevant
      covariates and explained 7% of the total variance. Trait temptation not IAT
      predicted subjective craving. Negative affect was unrelated to IAT scores, singly
      or in conjunction with measures of drinking restraint, contrary to predictions.
      In sum, implicit alcohol cognitions are related to attempts to restrict drinking
      not temptation to drink and are less strongly influenced by mood state.

PMID- 22369224
TI  - Age-based differences in treatment outcome among alcohol-dependent women.
AB  - The literature suggests that women are at higher risk for negative consequences
      from alcohol use than men and that these risks are compounded by age. The current
      study investigated how alcohol-dependent women from different age groups might
      differ in terms of baseline functioning and treatment response. The sample
      consisted of 181 participants drawn from two randomized clinical trials of
      cognitive-behavioral treatments for alcohol-dependent women. Demographic and
      psychopathology data were obtained at baseline using the SCID (Structured
      Clinical Interview for DSM disorders) I for Axis I disorders and the SCID II or
      Personality Disorders Questionnaire for Axis II disorders. Social networks data
      were collected using the Important People and Activities Interview. Drinking data
      were collected at baseline and follow-up using the Timeline Follow Back
      Interview. ANOVAs revealed that older women had better psychosocial functioning
      in terms of being better educated and reporting fewer Axis I disorders. Also,
      older women had more supportive social networks in terms of more people, a
      smaller percentage of heavy drinkers, and a nondrinking spouse. Older women
      reported a less severe lifetime substance use history with a later age of first
      drink, later onset of alcohol use disorders, fewer lifetime abuse/dependence
      items, and less drug use. However, they reported drinking more frequently and
      more heavily over the 90 days prior to treatment. Finally, older women were more
      compliant with treatment and responded better by reducing drinking frequency and
      percentage of heavy drinking days. Suggestions to enhance treatment efficacy for
      younger women are made as well as suggestions for future research.

PMID- 22369225
TI  - Subacute cutaneous lupus erythematosus associated with radioiodine treatment.
AB  - Subacute cutaneous lupus erythematosus (SCLE) is characterized by nonscarring,
      photodistributed, annular or papulosquamous plaques with antibodies to Ro/SS-A
      antigen. We report a case of SCLE associated with radioiodine treatment.

PMID- 22369226
TI  - GJB2 (Connexin-26) mutations are not frequent among hearing impaired patients in
      east Greenland.
AB  - OBJECTIVE: Investigate genetic causes of HI among the Inuit populations in the
      Arctic with a high prevalence of hearing impairment (HI). DESIGN: A cross
      sectional survey with population-based controls. STUDY SAMPLE: Forty-five
      patients, with sensorineural or mixed HI and an available blood sample for GJB2
      sequencing from DNA, were selected from 166 east Greenlanders by specialist
      audiology examination, including pure-tone air and bone conduction audiometry
      from 125 Hz to 8000 Hz. Controls were 108 east- and 109 west-Greenlanders.
      RESULTS: Forty-five patients with HI were included, 24 males and 21 females.
      Median age was 35 years (range: 5-76). The c.35delG allele frequency was 3.3%.
      One patient, homozygous for the c.35delG GJB2 mutation, had bilateral congenital
      profound HI. Another with mixed HI was heterozygous for the same mutation. Three
      were heterozygous for the p.V27I variant and one was heterozygous for the p.V153I
      variant. The frequency of the c.35delG mutation in the controls varied between
      0.5% in west Greenland to 2.3% in east Greenland. CONCLUSION: The c.35delG GJB2
      mutation occurs in Greenland with low frequency. We conclude the main causes
      behind the prevalence of HI in this population are chronic otitis media, noise
      traumas, and/or unidentified genetic causes.

PMID- 22369227
TI  - Quality of life and functional status in patients with advanced cancer admitted
      to hospice home care in Malaysia: a cross-sectional study.
AB  - Cancer patients more than often experience poor quality of life after diagnosis
      and treatment of cancer. As the disease progresses quality of life issues become
      important. This cross-sectional study assessed various features of quality of
      life among 61 (33 women and 28 men) patients with advanced cancer cared by
      selected hospices in Peninsular Malaysia. The Hospice Quality of Life Index was
      used to assess quality of life. The mean total Hospice Quality of Life Index
      score for all subjects was 189.9 +/- 51.7. The possible scores range from 0 to
      280. The most problem areas in these patients were in the domain of functional
      well-being, followed by psychophysiological and social/spiritual domain. Patients
      with advanced cancer have a diminished quality of life. These findings suggest
      that there is a need for improving quality of life in terminally ill cancer
      patients in hospice care.

PMID- 22369228
TI  - A critical evaluation of c as a measure of mnemonic resolution.
AB  - It is known that visual working memory capacity is limited, but the nature of
      this limit remains a subject of controversy. Increasingly, two factors are
      thought to limit visual memory: an object-based limit associated with so-called
      "slots" models, and an information-based limit associated with resource models.
      Recently, Barton, Ester, and Awh (2009) introduced a measure of mnemonic
      resolution, which they dubbed c. We show here that c is critically flawed, and
      cannot be interpreted as a measure of resolution. We recommend strongly against
      its use and interpretation, and suggest alternatives approaches for researchers
      who want to explore mnemonic resolution.

PMID- 22369229
TI  - Discrete events as units of perceived time.
AB  - In visual images, we perceive both space (as a continuous visual medium) and
      objects (that inhabit space). Similarly, in dynamic visual experience, we
      perceive both continuous time and discrete events. What is the relationship
      between these units of experience? The most intuitive answer may be similar to
      the spatial case: time is perceived as an underlying medium, which is later
      segmented into discrete event representations. Here we explore the opposite
      possibility--that our subjective experience of time itself can be influenced by
      how durations are temporally segmented, beyond more general effects of change and
      complexity. We show that the way in which a continuous dynamic display is
      segmented into discrete units (via a path shuffling manipulation) greatly
      influences duration judgments, independent of psychophysical factors previously
      implicated in time perception, such as overall stimulus energy, attention and
      predictability. It seems that we may use the passage of discrete events--and the
      boundaries between them--in our subjective experience as part of the raw material
      for inferring the strength of the underlying "current" of time.

PMID- 22369230
TI  - Seed-mediated co-reduction: a versatile route to architecturally controlled
      bimetallic nanostructures.
AB  - Gold-palladium octopods and new concave and shape-controlled alloy nanostructures
      are synthesized by seed-mediated co-reduction, wherein two metal precursors are
      reduced in the presence of seeds that serve as preferential sites for the growth
      of the larger nanostructures. Here, the first comprehensive study of this
      technique is presented in a model Au-Pd system and provides insight into the
      mechanism of formation for these architecturally distinct nanocrystals. A
      systematic evaluation of synthesis conditions decoupled the roles of (i) Au:Pd
      precursor ratio, (ii) reaction pH, and (iii) capping agent concentration in
      morphology development. These factors provide control of growth kinetics and
      ultimately the morphology and composition of the final nanostructures.
      Significantly, elucidating the overgrowth processes during seed-mediated co
      reduction will lead to the synthesis of other architecturally controlled
      bimetallic nanocrystals.

PMID- 22369232
TI  - Stop laughing! Humor perception with and without expressive suppression.
AB  - The neurophysiological study of emotion regulation focused on the strategy of
      reappraisal-i.e., the cognitive reinterpretation of a stimulus. Reappraisal
      reduces emotional expression, the experience of both negative and positive
      feelings, and the amplitude of an event-related potential (ERP)-the late positive
      potential (LPP). In contrast, the strategy of expressive suppression (ES), being
      the inhibition of emotional expression, has been reported to reduce subjective
      feelings of positive, but not negative emotion, and has not yet been investigated
      with ERPs. We focused on the LPP to assess the correlates of ES in the context of
      humor perception. Twenty-two female participants rated sequences of humorous (H)
      and non-humorous (NH) pictures, while their zygomaticus muscle was recorded. A
      spontaneous (SP) condition, in which participants attended naturally to the
      pictures, resulted in higher ratings of funniness, increased smiling, and
      increased LPP amplitude for H compared to NH stimuli. An ES condition, in which
      participants suppressed their facial reactions, resulted in reduced smiling,
      without affecting subjective ratings. LPP amplitude did not differ between H and
      NH stimuli during ES, suggesting equal allocation of processing resources to both
      stimuli. These results suggest that, similarly to reappraisal, ES modifies the
      way the brain processes positive emotional stimuli.

PMID- 22369233
TI  - Synthesis, biological evaluation, and structure-activity relationships of 2-[2
      (benzoylamino)benzoylamino]benzoic acid analogues as inhibitors of adenovirus
      replication.
AB  - 2-[2-Benzoylamino)benzoylamino]benzoic acid (1) was previously identified as a
      potent and nontoxic antiadenoviral compound (Antimicrob. Agents Chemother. 2010,
      54, 3871). Here, the potency of 1 was improved over three generations of
      compounds. We found that the ortho, ortho substituent pattern and the presence of
      the carboxylic acid of 1 are favorable for this class of compounds and that the
      direction of the amide bonds (as in 1) is obligatory. Some variability in the N
      terminal moiety was tolerated, but benzamides appear to be preferred. The
      substituents on the middle and C-terminal rings were varied, resulting in two
      potent inhibitors, 35g and 35j, with EC(50) = 0.6 MUM and low cell toxicity.

PMID- 22369235
TI  - Transferable force field for carboxylate esters: application to fatty acid
      methylic ester phase equilibria prediction.
AB  - In this work, a new transferable united-atoms force field for carboxylate esters
      is proposed. All Lennard-Jones parameters are reused from previous
      parametrizations of the AUA4 force field, and only a unique set of partial
      electrostatic charges is introduced for the ester chemical function. Various
      short alkyl-chain esters (methyl acetate, ethyl acetate, methyl propionate, ethyl
      propionate) and two fatty acid methylic esters (methyl oleate and methyl
      palmitate) are studied. Using this new force field in Monte Carlo simulations, we
      show that various pure compound properties are accurately predicted: saturated
      liquid densities, vapor pressures, vaporization enthalpies, critical properties,
      liquid-vapor surface tensions. Furthermore, a good accuracy is also obtained in
      the prediction of binary mixture pressure-composition diagrams, without
      introducing empirical binary interaction parameters. This highlights the
      transferability of the proposed force field and gives the opportunity to simulate
      mixtures of industrial interest: a demonstration is performed through the
      simulation of the methyl oleate + methanol mixture involved in the purification
      sections of biodiesel production processes.

PMID- 22369234
TI  - NeuroD2 regulates the development of hippocampal mossy fiber synapses.
AB  - BACKGROUND: The assembly of neural circuits requires the concerted action of both
      genetically determined and activity-dependent mechanisms. Calcium-regulated
      transcription may link these processes, but the influence of specific
      transcription factors on the differentiation of synapse-specific properties is
      poorly understood. Here we characterize the influence of NeuroD2, a calcium
      dependent transcription factor, in regulating the structural and functional
      maturation of the hippocampal mossy fiber (MF) synapse. RESULTS: Using NeuroD2
      null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a
      critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF
      inputs. We also use electrophysiological recordings from CA3 neurons while
      stimulating MF axons to show that NeuroD2 regulates the differentiation of
      functional properties at the MF synapse. Finally, we find that NeuroD2 regulates
      PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo
      reproduces CA3 neuron spine defects observed in NeuroD2 null mice. CONCLUSION:
      These experiments identify NeuroD2 as a key transcription factor that regulates
      the structural and functional differentiation of MF synapses in vivo.

PMID- 22369236
TI  - Adsorption and detection of sport doping drugs on metallic plasmonic
      nanoparticles of different morphology.
AB  - A comparative study of different plasmonic nanoparticles with different
      morphologies (nanospheres and triangular nanoprisms) and metals (Ag and Au) was
      done in this work and applied to the ultrasensitive detection of
      aminoglutethimide (AGI) drug by surface enhanced Raman spectroscopy (SERS) and
      plasmon resonance. AGI is an aromatase inhibitor used as an antitumoral drug with
      remarkable pharmacological interest and also in illegal sport doping. The
      application of very sensitive spectroscopic techniques based on the localization
      of an electromagnetic field on plasmonic nanoparticles confirms the previous
      study of the adsorption of drugs onto a metal surface due to the near field
      character of these techniques. The adsorption of AGI on the above substrates was
      investigated at different pH values and surface coverages, and the results were
      analyzed on the basis of AGI/metal affinity, considering the interaction
      mechanism, the existence of two binding sites in AGI, and the influence of the
      interface on the adsorption in terms of surface charge due to the presence of
      other ions linked to the surface. Finally, a comparative quantitative detection
      of AGI was performed on both spherical and triangular nanoprism nanoparticles,
      and a limit of detection lower than those reported so far was deduced on the
      latter nanoparticles.

PMID- 22369237
TI  - INDUS - a composition-based approach for rapid and accurate taxonomic
      classification of metagenomic sequences.
AB  - BACKGROUND: Taxonomic classification of metagenomic sequences is the first step
      in metagenomic analysis. Existing taxonomic classification approaches are of two
      types, similarity-based and composition-based. Similarity-based approaches,
      though accurate and specific, are extremely slow. Since, metagenomic projects
      generate millions of sequences, adopting similarity-based approaches becomes
      virtually infeasible for research groups having modest computational resources.
      In this study, we present INDUS - a composition-based approach that incorporates
      the following novel features. First, INDUS discards the 'one genome-one
      composition' model adopted by existing compositional approaches. Second, INDUS
      uses 'compositional distance' information for identifying appropriate assignment
      levels. Third, INDUS incorporates steps that attempt to reduce biases due to
      database representation. RESULTS: INDUS is able to rapidly classify sequences in
      both simulated and real metagenomic sequence data sets with classification
      efficiency significantly higher than existing composition-based approaches.
      Although the classification efficiency of INDUS is observed to be comparable to
      those by similarity-based approaches, the binning time (as compared to alignment
      based approaches) is 23-33 times lower. CONCLUSION: Given it's rapid execution
      time, and high levels of classification efficiency, INDUS is expected to be of
      immense interest to researchers working in metagenomics and microbial ecology.
      AVAILABILITY: A web-server for the INDUS algorithm is available at
      http://metagenomics.atc.tcs.com/INDUS/

PMID- 22369240
TI  - Sustainable waste and materials management: national policy and global
      perspective.

PMID- 22369239
TI  - Altered gene expression profiles in the hippocampus and prefrontal cortex of type
      2 diabetic rats.
AB  - BACKGROUND: There has been an increasing body of epidemiologic and biochemical
      evidence implying the role of cerebral insulin resistance in Alzheimer-type
      dementia. For a better understanding of the insulin effect on the central nervous
      system, we performed microarray-based global gene expression profiling in the
      hippocampus, striatum and prefrontal cortex of streptozotocin-induced and
      spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2
      diabetes, respectively. RESULTS: Following pathway analysis and validation of
      gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus,
      such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling
      protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2,
      protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1), CD47
      (Cluster of Differentiation 47) and the RET (Rearranged During Transfection)
      protooncogene, were found to exhibit altered expression levels in type 2 diabetic
      model animals in comparison to non-diabetic control animals. These gene lists
      proved to be partly overlapping and encompassed genes related to
      neurotransmission, lipid metabolism, neuronal development, insulin secretion,
      oxidative damage and DNA repair. On the other hand, no significant alterations
      were found in the transcriptomes of the corpus striatum in the same animals.
      Changes in the cerebral gene expression profiles seemed to be specific for the
      type 2 diabetic model, as no such alterations were found in streptozotocin
      treated animals. CONCLUSIONS: According to our knowledge this is the first
      characterization of the whole-genome expression changes of specific brain regions
      in a diabetic model. Our findings shed light on the complex role of insulin
      signaling in fine-tuning brain functions, and provide further experimental
      evidence in support of the recently elaborated theory of type 3 diabetes.

PMID- 22369241
TI  - Structures of new triterpenoids and cytotoxicity activities of the isolated major
      compounds from the fruit of Momordica charantia L.
AB  - Two new cucurbitane-type triterpene glycosides, charantagenins D (1) and E (2),
      and one new sterol, 7-oxo-stigmasta-5,25-diene-3-O-beta-d-glucopyranoside (3),
      were isolated from the fruit of  Momordica charantia  L. together with another
      eight known compounds. Their structures were determined on the basis of spectral
      analysis. Cytotoxicity activities of the isolated major compounds were evaluated
      against lung cancer cell line A549, glioblastoma cell line U87, and hepatoma
      carcinoma cell line Hep3B by using a 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) in vitro assay. Results showed compounds 1 and
      7 (goyaglycoside d) with an -OMe substituent group in the side chain exhibited
      significant cytotoxic activities against cancer cells. Impressively, the IC(50)
      values of the new compound 1 to A549, U87, and Hep3B were 1.07, 1.08, and 14.01
      MUmol/L, respectively, which were much lower than those of other tested
      compounds.

PMID- 22369242
TI  - "Zeoball" [Sn36Ge24Se132]24-: a molecular anion with zeolite-related composition
      and spherical shape.
AB  - Ionothermal reactions of [Ge(4)Se(10)](4-) with SnCl(4).5H(2)O yielded
      [BMMIm](24)[Sn(36)Ge(24)Se(132)] (ZBT-1) and [BMIm](24)[Sn(32.5)Ge(27.5)Se(132)]
      [ZBT-2; B(M)MIm = 1-butyl-(2,)3-(di)methylimidazolium]. These contain the largest
      known discrete polyanion consisting only of main-group elements. In spite of a
      zeolite-related composition, the 192-atom "zeoball" anion adopts a spherical
      shape, which has been unprecedented in the chemistry of zeolites and their
      homologues and relatives. Preliminary studies indicated that ZBT-1 traps I(2)
      molecules and induces heterolytic I-I bond cleavage.

PMID- 22369245
TI  - Feminism and psychology: analysis of a half-century of research on women and
      gender.
AB  - Starting in the 1960s, feminists argued that the discipline of psychology had
      neglected the study of women and gender and misrepresented women in its research
      and theories. Feminists also posed many questions worthy of being addressed by
      psychological science. This call for research preceded the emergence of a new and
      influential body of research on gender and women that grew especially rapidly
      during the period of greatest feminist activism. The descriptions of this
      research presented in this article derive from searches of the journal articles
      cataloged by PsycINFO for 1960-2009. These explorations revealed (a) a
      concentration of studies in basic research areas investigating social behavior
      and individual dispositions and in many applied areas, (b) differing trajectories
      of research on prototypical topics, and (c) diverse theoretical orientations that
      authors have not typically labeled as feminist. The considerable dissemination of
      this research is evident in its dispersion beyond gender-specialty journals into
      a wide range of other journals, including psychology's core review and theory
      journals, as well as in its coverage in introductory psychology textbooks. In
      this formidable body of research, psychological science has reflected the
      profound changes in the status of women during the last half-century and
      addressed numerous questions that these changes have posed. Feminism served to
      catalyze this research area, which grew beyond the bounds of feminist psychology
      to incorporate a very large array of theories, methods, and topics.

PMID- 22369243
TI  - Congruence as a measurement of extended haplotype structure across the genome.
AB  - BACKGROUND: Historically, extended haplotypes have been defined using only a few
      data points, such as alleles for several HLA genes in the MHC. High-density SNP
      data, and the increasing affordability of whole genome SNP typing, creates the
      opportunity to define higher resolution extended haplotypes. This drives the need
      for new tools that support quantification and visualization of extended
      haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP
      data across the major histocompatibility complex (MHC) for 2,300 complete
      families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we
      developed software for studying extended haplotypes. METHODS: The software,
      called ExHap (Extended Haplotype), uses a similarity measurement we term
      congruence to identify and quantify long-range allele identity. Using ExHap, we
      analyzed congruence in both the T1DGC data and family-phased data from the
      International HapMap Project. RESULTS: Congruent chromosomes from the T1DGC data
      have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64
      megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined
      haplotype groups have > 50% congruent chromosomes in this region. For example,
      92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to
      HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both
      CEU and YRI cohorts from the International HapMap Project, identifying multiple
      candidate extended haplotypes. CONCLUSIONS: Long-range congruence is not unique
      to the MHC region. Patterns of allele identity on phased chromosomes provide a
      simple, straightforward approach to visually and quantitatively inspect complex
      long-range structural patterns in the genome. Such patterns aid the biologist in
      appreciating genetic similarities and differences across cohorts, and can lead to
      hypothesis generation for subsequent studies.

PMID- 22369244
TI  - Dissecting genetic architecture of grape proanthocyanidin composition through
      quantitative trait locus mapping.
AB  - BACKGROUND: Proanthocyanidins (PAs), or condensed tannins, are flavonoid
      polymers, widespread throughout the plant kingdom, which provide protection
      against herbivores while conferring organoleptic and nutritive values to plant
      derived foods, such as wine. However, the genetic basis of qualitative and
      quantitative PA composition variation is still poorly understood. To elucidate
      the genetic architecture of the complex grape PA composition, we first carried
      out quantitative trait locus (QTL) analysis on a 191-individual pseudo-F1
      progeny. Three categories of PA variables were assessed: total content,
      percentages of constitutive subunits and composite ratio variables. For nine
      functional candidate genes, among which eight co-located with QTLs, we performed
      association analyses using a diversity panel of 141 grapevine cultivars in order
      to identify causal SNPs. RESULTS: Multiple QTL analysis revealed a total of 103
      and 43 QTLs, respectively for seed and skin PA variables. Loci were mainly of
      additive effect while some loci were primarily of dominant effect. Results also
      showed a large involvement of pairwise epistatic interactions in shaping PA
      composition. QTLs for PA variables in skin and seeds differed in number,
      position, involvement of epistatic interaction and allelic effect, thus revealing
      different genetic determinisms for grape PA composition in seeds and skin.
      Association results were consistent with QTL analyses in most cases: four out of
      nine tested candidate genes (VvLAR1, VvMYBPA2, VvCHI1, VvMYBPA1) showed at least
      one significant association with PA variables, especially VvLAR1 revealed as of
      great interest for further functional investigation. Some SNP-phenotype
      associations were observed only in the diversity panel. CONCLUSIONS: This study
      presents the first QTL analysis on grape berry PA composition with a comparison
      between skin and seeds, together with an association study. Our results suggest a
      complex genetic control for PA traits and different genetic architectures for
      grape PA composition between berry skin and seeds. This work also uncovers novel
      genomic regions for further investigation in order to increase our knowledge of
      the genetic basis of PA composition.

PMID- 22369246
TI  - An asymptomatic nodule on the upper thigh.

PMID- 22369247
TI  - Legumes select symbiosis island sequence variants in Bradyrhizobium.
AB  - Bradyrhizobium strains sampled from 14 legume genera native to eastern North
      America showed substantial host-related phylogenetic clustering at three loci in
      the symbiotic island (SI) region (nodC, nifD, nifH), indicating selection of
      distinct suites of SI lineages by different legumes. Bacteria assorted
      consistently with particular legumes across two regions separated by 800 km,
      implying recurrent assembly of the same symbiotic combinations. High genetic
      polymorphism of all three SI loci relative to four nonsymbiotic loci supported
      the inference that a form of multiple-niche balancing selection has acted on the
      SI region, arising from differential symbiont utilization by different legume
      taxa. Extensive discordance between the tree for SI variants and a phylogenetic
      tree inferred for four housekeeping loci implied that lateral transfer of the
      symbiosis island region has been common (at least 26 transfer events among 85
      Bradyrhizobium strains analysed). Patterns of linkage disequilibrium also
      supported the conclusion that recombination has impacted symbiotic and
      nonsymbiotic regions unequally. The high prevalence of lateral transfer suggests
      that acquisition of a novel SI variant may often confer a strong selective
      advantage for recipient cells.

PMID- 22369248
TI  - Nature of the chemical bond in transition: dissection of radical-molecule
      reactivity.
AB  - A complete method for quantifying the Born-Oppenheimer barriers of radical-
      molecule abstraction reactions is derived from first principles with the dual
      objectives of analytical prediction and conceptual understanding. Expanding upon
      the work of Donahue et al. (J. Phys. Chem. A 1998, 102, 3923-3933) this treatment
      uses the strategic construction of reactant-like and product-like wave functions
      to evaluate the coupling between crossing diabatic states. The overall reaction
      coordinate is evaluated in a modular fashion, whereby each region is analyzed
      within the context of its governing physics.

PMID- 22369249
TI  - Portal vein thrombosis in 33 dogs: 1998-2011.
AB  - BACKGROUND: Portal vein thrombosis (PVT) has been reported infrequently in dogs.
      OBJECTIVES: To characterize the presentation, associated disease conditions, and
      outcome in dogs with PVT. ANIMALS: Client-owned dogs with a diagnosis of PVT and
      a complete medical record. METHODS: Records were retrospectively analyzed for
      presentation, history, physical examination, clinicopathologic data, diagnostic
      imaging, treatment, and outcome. RESULTS: Thirty-three dogs were included. Common
      clinical signs were vomiting, diarrhea, abdominal pain, ascites, and signs of
      hypovolemic shock. Associated disease conditions included hepatic (14/33),
      neoplastic (7/33), immune (5/33), and infectious (4/33) diseases, protein-losing
      nephropathy (3/33), hyperadrenocorticism (2/33), protein-losing enteropathy
      (1/33), and pancreatitis (1/33). Fourteen dogs were receiving glucocorticoids at
      the time of diagnosis. Twenty-nine dogs had at least 1 predisposing condition for
      venous thrombosis, and 11 had 2 or more. Thrombocytopenia (24/33), increased
      liver enzyme activity (23/33), and hypoalbuminemia (20/33) were common laboratory
      abnormalities. Clinical syndromes at the time of PVT diagnosis included shock
      (16/33), systemic inflammatory response syndrome (SIRS), (13/33) and disseminated
      intravascular coagulation (3/33). Twenty-four dogs had acute and 9 had chronic
      PVT. Multiple thrombi were found in 17/33 dogs. Nineteen dogs survived to
      discharge. Dogs treated with anticoagulant therapy were more likely, whereas
      those with acute PVT, multiple thromboses or SIRS were less likely to survive.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Hepatic disease is a common pre-existing
      condition in dogs with PVT. PVT should be considered in dogs with risk factors
      for venous thrombosis presenting with abdominal pain, ascites, and
      thrombocytopenia. Studies evaluating anticoagulant therapy in the management of
      PVT are warranted.

PMID- 22369251
TI  - Scabies and pediculosis: neglected diseases to highlight.

PMID- 22369250
TI  - Molecular dynamics study of the archaeal aquaporin AqpM.
AB  - BACKGROUND: Aquaporins are a large family of transmembrane channel proteins that
      are present throughout all domains of life and are implicated in human disorders.
      These channels, allow the passive but selective movement of water and other small
      neutral solutes across cell membranes. Aquaporins have been classified into two
      sub-families: i) strict aquaporins that only allow the passage of water and ii)
      the less selective aquaglyceroporins that transport water and other neutral
      solutes, such as glycerol, CO2 or urea. Recently, the identification and
      characterization of a number of archaeal and bacterial aquaporins suggested the
      existence of a third sub-family; one that is neither a strict aquaporin nor an
      aquaglyceroporin. The function and phylogeny of this third family is still a
      matter of debate. RESULTS: Twenty nanosecond molecular dynamics (MD) simulation
      of a fully hydrated tetramer of AqpM embedded in a lipid bilayer permitted
      predictions to be made of key biophysical parameters including: single channel
      osmotic permeability constant (pf), single channel diffusive permeability
      constant (pd), channel radius, potential water occupancy of the channel and water
      orientation inside the pore. These properties were compared with those of well
      characterized representatives of the two main aquaporin sub-families. Results
      show that changes in the amino acid composition of the aromatic/arginine region
      affect the size and polarity of the selectivity filter (SF) and could help
      explain the difference in water permeability between aquaporins. In addition, MD
      simulation results suggest that AqpM combines characteristics of strict
      aquaporins, such as the narrow SF and channel radius, with those of
      aquaglyceroporins, such as a more hydrophobic and less polar SF. CONCLUSIONS: MD
      simulations of AqpM extend previous evidence that this archaeal aquaporin
      exhibits hybrid features intermediate between the two known aquaporin sub
      families, supporting the idea that it may constitute a member of a novel class of
      aquaporins.

PMID- 22369253
TI  - NPY modulates PYY function in the regulation of energy balance and glucose
      homeostasis.
AB  - AIMS: Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide
      YY (PYY) have been implicated in the regulation of energy balance and glucose
      homeostasis. However, despite similar affinities for the same Y receptors, the co
      ordinated actions of these two peptides in energy and glucose homeostasis remain
      largely unknown. METHODS: To investigate the mechanisms and possible interactions
      between PYY with NPY in the regulation of these processes, we utilized NPY/PYY
      single and double mutant mouse models and examined parameters of energy balance
      and glucose homeostasis. RESULTS: PYY(-/-) mice exhibited increased fasting
      induced food intake, enhanced fasting and oral glucose-induced serum insulin
      levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-)
      mice. Interestingly, whereas PYY deficiency-induced impairment in insulin
      tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on
      fasting-induced food intake and serum insulin concentrations at baseline and
      after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting
      that NPY signalling may be required for PYY's action on insulin secretion and
      fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or
      PYY(-/-) mice had significantly decreased daily food intake, indicating
      interactive control by NPY and PYY on spontaneous food intake. Furthermore, both
      NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange
      ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(
      /-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via
      partly shared mechanisms. Overall, physical activity and energy expenditure,
      however, are not significantly altered by NPY and PYY single or double
      deficiencies. CONCLUSIONS: These findings show significant and diverse
      interactions between NPY and PYY signalling in the regulation of different
      aspects of energy balance and glucose homeostasis.

PMID- 22369254
TI  - Lexical and sublexical semantic preview benefits in Chinese reading.
AB  - Semantic processing from parafoveal words is an elusive phenomenon in alphabetic
      languages, but it has been demonstrated only for a restricted set of noncompound
      Chinese characters. Using the gaze-contingent boundary paradigm, this experiment
      examined whether parafoveal lexical and sublexical semantic information was
      extracted from compound preview characters. Results generalized parafoveal
      semantic processing to this representative set of Chinese characters and extended
      the parafoveal processing to radical (sublexical) level semantic information
      extraction. Implications for notions of parafoveal information extraction during
      Chinese reading are discussed.

PMID- 22369255
TI  - Expanding on the mental number line: zero is perceived as the "smallest".
AB  - The representation of 0 in healthy adults was studied with the physical
      comparison task. Automatic processing of numbers, as indicated by the size
      congruity effect, was used for detecting the basic numerical representations
      stored in long-term memory. The size congruity effect usually increases with
      numerical distance between the physically compared numbers. This increase was
      attenuated for comparisons to 0 or 1 (but not to 2) when they were perceived as
      the smallest number in the set. Furthermore, the size congruity effect was
      enlarged in these cases. These results indicate an end effect in automatic
      processing of numbers and suggest that 0, or 1 in the absence of 0, is perceived
      as the smallest entity on the mental number line. The implications of these
      findings are discussed with regard to models of number representation.

PMID- 22369256
TI  - Circulating nucleic acids and evolution.
AB  - INTRODUCTION: J.B. Lamarck in 1809 was the first to present a theory of
      evolution. He proposed it was due to the adaptation of species to environmental
      changes, this adaptation being acquired by the offspring. In 1868, Darwin
      suggested that cells excrete gemmules, which circulate through the body and reach
      the gonads where they are transmitted to the next generation. His main argument
      came from graft hybrids. AREAS COVERED: In the fifties and sixties, Russian
      geneticists, rejecting neo-Darwinism, said that acquired characteristics were the
      basis of evolution. The main experiments on which they based their theory were
      the transmission of hereditary characteristics by a special technique of grafting
      between two varieties of plants. We repeated this kind of experiment and also
      succeeded in obtaining hereditary modifications of the pupil plants that acquired
      some characteristics of the mentor variety. Rather than adopting the views of the
      Russian scientists, we suggested that DNA was circulating between the mentor and
      pupil plants. Hirata's group have shown recently, by using molecular techniques
      such as cloning, RFLP PCR and sequencing some genes of their graft hybrids of
      pepper plants, that transfer of informative molecules from the mentor to the
      pupil plant does exist. Nucleic acids are actively released by cells; they
      circulate in the body. They can transform oncogenically or trigger antibody
      response but the only genetic transformation showing that DNA can go from the
      soma to the germen comes from graft hybrids. EXPERT OPINION: This suggests that
      circulating nucleic acids, in this case DNA, like Darwin's gemmules, play a role
      in the mechanism of evolution.

PMID- 22369257
TI  - Cross-talk between AMPK and mTOR in regulating energy balance.
AB  - Energy balance is maintained by a complex homeostatic system involving some
      signaling pathways and "nutrient sensors" in multiple tissues and organs. Any
      defect associated with the pathways can lead to metabolic disorders including
      obesity, type 2 diabetes, and the metabolic syndrome. The 5'-adenosine
      monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin
      (mTOR) appear to play a significant role in the intermediary metabolism of these
      diseases. AMPK is involved in the fundamental regulation of energy balance at the
      whole body level by responding to hormonal and nutrient signals in the central
      nervous system and peripheral tissues that modulate food intake and energy
      expenditure. Mammalian target of rapamycin (mTOR),is one of the downstream
      targets of AMPK functions as an intracellular nutrient sensor to control protein
      synthesis, cell growth, and metabolism. Recent research demonstrated the possible
      interplay between mTOR and AMPK signaling pathways. In this review, we will
      present current knowledge of AMPK and mTOR pathways in regulating energy balance
      and demonstrate the convergence between these two pathways.

PMID- 22369258
TI  - The role of diet in prevention and management of type 2 diabetes: implications
      for public health.
AB  - The aim of this review is to examine the current scientific knowledge on the
      relationship between diet and Type 2 diabetes and consider further implications
      for public health. The review focuses on the main nutritional elements which have
      been identified as significant in the prevention and management of Type 2
      diabetes. Research findings on the role of carbohydrate, fiber, alcohol, and
      individual fatty acids are discussed, while the role of specific micro-nutrients
      and the influence of obesity are comprehensively presented. The association
      between dietary habits and Type 2 diabetes etiology and management is also
      reviewed, in order to examine the positive effects of adherence to a healthy
      dietary pattern, including the plausible role of the Mediterranean diet.

PMID- 22369259
TI  - Water dynamics in fresh and frozen yeasted dough.
AB  - Water is an integral part of wheat flour dough-the amount, physical state, and
      location of water are crucial to the formation of a dough that will hold gas and
      produce an open, aerated crumb structure in the final product. This has been
      understood for centuries by craft bakers, who were highly attuned to the "feel"
      of dough in their hands. In the 20th century, empirical instruments were invented
      that simulated part of the breadmaking process, and their limited predictive
      capacity made them valuable quality control tools. During the latter decades of
      the 20th century the cost and availability of advanced instrumental methods for
      characterizing foods improved dramatically, and facilitated a "fundamental
      science" approach to food research. The physicochemical mechanisms by which water
      exerts such a strong influence on the character of dough are now better
      understood. This review contrasts the empirical and fundamental view points, and
      summarizes recent knowledge about the roles of water in the manufacture of fresh
      and frozen yeasted dough.

PMID- 22369260
TI  - Folate-binding protein in milk: a review of biochemistry, physiology, and
      analytical methods.
AB  - Folate-binding protein (FBP) was discovered in cow's milk around 40 years ago.
      Bovine FBP belongs to a family of several folate-binding proteins. In milk, it is
      a soluble whey protein with the ability to sequester folate from blood plasma.
      Bovine FBP is a well-characterized protein in terms of amino acid sequence and
      binding characteristics. Affinity and binding kinetics towards various folate
      forms have been intensively studied because they are crucial in using bovine FBP
      as an analytical tool. Shortly after the identification of bovine FBP, a
      competitive protein-binding assay for measuring serum and blood folate
      concentrations was introduced. Another analytical application of bovine FBP is in
      affinity chromatography, as a clean-up/concentration step for analysis of folates
      in foods and biological samples by liquid chromatographic methods. Concentrations
      of FBP in milk and dairy products have been determined by ELISA and Surface
      Plasmon Resonance-biosensor techniques. Since the initial reports of FBP in cow's
      milk, its physiological role has been discussed, especially regarding its effects
      on folate absorption from milk and dairy products. This review summarizes recent
      biochemical, analytical, food science, and nutritional advances regarding folate
      binding protein in milk.

PMID- 22369261
TI  - Recent advances in biopolymers and biopolymer-based nanocomposites for food
      packaging materials.
AB  - Plastic packaging for food and non-food applications is non-biodegradable, and
      also uses up valuable and scarce non-renewable resources like petroleum. With the
      current focus on exploring alternatives to petroleum and emphasis on reduced
      environmental impact, research is increasingly being directed at development of
      biodegradable food packaging from biopolymer-based materials. The proposed paper
      will present a review of recent developments in biopolymer-based food packaging
      materials including natural biopolymers (such as starches and proteins),
      synthetic biopolymers (such as poly lactic acid), biopolymer blends, and
      nanocomposites based on natural and synthetic biopolymers. The paper will discuss
      the various techniques that have been used for developing cost-effective
      biodegradable packaging materials with optimum mechanical strength and oxygen and
      moisture barrier properties. This is a timely review as there has been a recent
      renewed interest in research studies, both in the industry and academia, towards
      development of a new generation of biopolymer-based food packaging materials with
      possible applications in other areas.

PMID- 22369262
TI  - A model for communication of sensory quality in the seafood processing chain.
AB  - Sensory quality has a key influence of consumer perception of a product. It is
      therefore of great importance for the processing industry that the sensory
      quality fulfils the expectations of the consumer. Sensory evaluations are the
      ultimate tool to measure and communicate sensory quality, but it is generally not
      fully implemented in the chain from catch to consumer. The importance of
      communicating sensory demands and results from evaluations in the seafood
      processing chain is described and a Seafood Sensory Quality Model (SSQM) is
      suggested as a communication tool.

PMID- 22369263
TI  - Tyramine and phenylethylamine biosynthesis by food bacteria.
AB  - Tyramine poisoning is caused by the ingestion of food containing high levels of
      tyramine, a biogenic amine. Any foods containing free tyrosine are subject to
      tyramine formation if poor sanitation and low quality foods are used or if the
      food is subject to temperature abuse or extended storage time. Tyramine is
      generated by decarboxylation of the tyrosine through tyrosine decarboxylase (TDC)
      enzymes derived from the bacteria present in the food. Bacterial TDC have been
      only unequivocally identified and characterized in Gram-positive bacteria,
      especially in lactic acid bacteria. Pyridoxal phosphate (PLP)-dependent TDC
      encoding genes (tyrDC) appeared flanked by a similar genetic organization in
      several species of lactic acid bacteria, suggesting a common origin by a single
      mobile genetic element. Bacterial TDC are also able to decarboxylate
      phenylalanine to produce phenylethylamine (PEA), another biogenic amine. The
      molecular knowledge of the genes involved in tyramine production has led to the
      development of molecular methods for the detection of bacteria able to produce
      tyramine and PEA. These rapid and simple methods could be used for the analysis
      of the ability to form tyramine by bacteria in order to evaluate the potential
      risk of tyramine biosynthesis in food products.

PMID- 22369264
TI  - The dynamics of elite paddling on a kayak simulator.
AB  - During kayak paddling, athletes attempt to maximize kayak velocity with the
      generation of optimal paddle forces. The aim of the current study was to examine
      ten elite kayakers and identify a number of key biomechanical performance
      variables during maximal paddling on a custom kayak simulator. These included
      analysing the effect of side (left and right) and period (beginning, middle, and
      end of the kayak simulation) on paddle force, paddle angle, mechanical
      efficiency, and stroke timing data. Paddle kinetics and kinematics were measured
      with strain gauge force transducers attached to either end of the ergometer
      paddle and using a 3D motion analysis system respectively. Results indicated a
      significantly greater mechanical efficiency during the right paddle stroke
      compared with the left (P < 0.025). In addition, analysing the effect of period,
      peak paddle force demonstrated a significant reduction when comparing the
      beginning to the middle and end of the simulated race respectively (P < 0.025).
      Examination of individual force profiles revealed considerable individuality,
      with significant variation in the time course of force application. Analysis of
      the profiles presented may provide meaningful feedback for kayakers and their
      coaches.

PMID- 22369265
TI  - i-rDNA: alignment-free algorithm for rapid in silico detection of ribosomal gene
      fragments from metagenomic sequence data sets.
AB  - BACKGROUND: Obtaining accurate estimates of microbial diversity using rDNA
      profiling is the first step in most metagenomics projects. Consequently, most
      metagenomic projects spend considerable amounts of time, money and manpower for
      experimentally cloning, amplifying and sequencing the rDNA content in a
      metagenomic sample. In the second step, the entire genomic content of the
      metagenome is extracted, sequenced and analyzed. Since DNA sequences obtained in
      this second step also contain rDNA fragments, rapid in silico identification of
      these rDNA fragments would drastically reduce the cost, time and effort of
      current metagenomic projects by entirely bypassing the experimental steps of
      primer based rDNA amplification, cloning and sequencing. In this study, we
      present an algorithm called i-rDNA that can facilitate the rapid detection of 16S
      rDNA fragments from amongst millions of sequences in metagenomic data sets with
      high detection sensitivity. RESULTS: Performance evaluation with data
      sets/database variants simulating typical metagenomic scenarios indicates the
      significantly high detection sensitivity of i-rDNA. Moreover, i-rDNA can process
      a million sequences in less than an hour on a simple desktop with modest hardware
      specifications. CONCLUSIONS: In addition to the speed of execution, high
      sensitivity and low false positive rate, the utility of the algorithmic approach
      discussed in this paper is immense given that it would help in bypassing the
      entire experimental step of primer-based rDNA amplification, cloning and
      sequencing. Application of this algorithmic approach would thus drastically
      reduce the cost, time and human efforts invested in all metagenomic projects.
      AVAILABILITY: A web-server for the i-rDNA algorithm is available at
      http://metagenomics.atc.tcs.com/i-rDNA/

PMID- 22369266
TI  - The antinociceptive effect of electroacupuncture at different depths of acupoints
      and under the needling surface.
AB  - BACKGROUND: The stimulation of acupoints along the meridians, but not the non
      acupoints outside of the meridians, produces analgesia. Although the acupoint is
      defined at the body surface, the exact location of the acupoints is not known.
      This study aims to examine whether the intensity and duration of the analgesic
      effect of electroacupuncture (EA) at the Zusanli (ST36) and Sanynjiao acupoints
      (SP6) change according to the depth of the stimulation. METHODS: Ninety-six male
      Wistar rats classified as responders were arbitrarily allocated into 16 groups of
      six rats each. Six groups received EA with uninsulated acupuncture needles (type
      I) or needles that were immersed in varnish and had the varnish circularly peeled
      0.2 mm from the tip (type II), 0.2 mm at 3 mm (type III) or 5 mm (type IV) from
      the tip, or 0.2 mm at 5 and 1 mm from the tip (type V), or EA sham for 20 min.
      Five groups received injection of formalin into the acupoint bilaterally at 5 mm
      or 1 mm deep into ST36, 5 mm below ST36 but inserting the needle at 45 degrees 
      to the skin surface, or 5 mm deep into non-acupoints. The remaining groups
      received intraplantar injection of saline, 1% or 2.5% formalin. The analgesic
      effects were measured by the rat tail-flick test. RESULTS: The bilateral
      stimulation of ST36 and SP6 by uninsulated or insulated needles produced
      analgesia in the rat tail-flick test. The stronger and longer lasting effects
      occurred after EA with the types I and V needles, or injection of formalin 5 mm
      deep into ST36. The remaining needles produced weaker and shorter lasting
      effects. Slow analgesic effect also occurred after formalin injection at 1 mm or
      5 mm below ST36 by inserting the needle at 45 degrees  to the skin surface.
      CONCLUSION: The experimental results suggest that the efficacy of the EA
      stimulation depends on the spatial distribution of the current density under the
      needling surface rather than only the acupoint or the depth of needling.

PMID- 22369267
TI  - Intramolecular base stacking of dinucleoside monophosphate anions in aqueous
      solution.
AB  - Time-dependent motions of 32 deoxyribodinucleoside and ribodinucleoside
      monophosphate anions in aqueous solution at 310 K were monitored during 40 ns
      using classical molecular dynamics (MD). In all studied molecules, spontaneous
      stacking/unstacking transitions occurred on a time-scale of 10 ns. To facilitate
      the structural analysis of the sampled configurations we defined a reaction
      coordinate for the nucleobase stacking that considers both the angle between the
      planes of the two nucleobases and the distance between their mass-centers.
      Additionally, we proposed a physically meaningful transient point on this
      coordinate that separates the stacked and unstacked states. We applied this
      definition to calculate free energies for stacking of all pairwise combinations
      of adenine, thymine (uracil), cytosine and guanine moieties embedded in studied
      dinucleosides monophosphate anions. The stacking equilibrium constants decreased
      in the order 5'-AG-3' > GA ~ GG ~ AA > GT ~ TG ~ AT ~ GC ~ AC > CG ~ TA > CA ~ TC
      ~ TT ~ CT ~ CC. The stacked conformations of AG occurred 10 times more frequently
      than its unstacked conformations. On the other hand, the last five base
      combinations showed a greater preference for the unstacked than the stacked
      state. The presence of an additional 2'-OH group in the RNA-based dinucleoside
      monophosphates increased the fraction of stacked complexes but decreased the
      compactness of the stacked state. The calculated MD trajectories were also used
      to reveal prevailing mutual orientation of the nucleobase dipoles in the stacked
      state.

PMID- 22369269
TI  - Simple method for preparing superhydrophobic paper: spray-deposited hydrophobic
      silica nanoparticle coatings exhibit high water-repellency and transparency.
AB  - Superhydrophobic and transparent coatings are deposited onto paper by spraying
      alcohol suspensions of SiO(2) nanoparticles. Superhydrophobicity depends on the
      aggregation states of nanoparticles, which are determined by the type of alcohol
      used in the suspensions. The superhydrophobicity of the paper is maintained after
      touching the paper with a bare finger.

PMID- 22369268
TI  - Multiple determinants for selective inhibition of apicomplexan calcium-dependent
      protein kinase CDPK1.
AB  - Diseases caused by the apicomplexan protozoans  Toxoplasma gondii  and 
      Cryptosporidium parvum  are a major health concern. The life cycle of these
      parasites is regulated by a family of calcium-dependent protein kinases (CDPKs)
      that have no direct homologues in the human host. Fortuitously, CDPK1 from both
      parasites contains a rare glycine gatekeeper residue adjacent to the ATP-binding
      pocket. This has allowed creation of a series of C3-substituted
      pyrazolopyrimidine compounds that are potent inhibitors selective for CDPK1 over
      a panel of human kinases. Here we demonstrate that selectivity is further
      enhanced by modification of the scaffold at the C1 position. The explanation for
      this unexpected result is provided by crystal structures of the inhibitors bound
      to CDPK1 and the human kinase c-SRC. Furthermore, the insight gained from these
      studies was applied to transform an alternative ATP-competitive scaffold lacking
      potency and selectivity for CDPK1 into a low nanomolar inhibitor of this enzyme
      with no activity against SRC.

PMID- 22369270
TI  - QT dispersion in patients with systemic lupus erythematosus: the impact of
      disease activity.
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) have increased
      cardiovascular morbidity and mortality. Although autopsy studies have documented
      that the heart is affected in most SLE patients, clinical manifestations occur in
      less than 10%. QT dispersion is a new parameter that can be used to assess
      homogeneity of cardiac repolarization and autonomic function. We compared the
      increase in QT dispersion in SLE patients with high disease activity and mild or
      moderate disease activity. METHODS AND RESULTS: One hundred twenty-four patients
      with SLE were enrolled in the study. Complete history and physical exam, ECG,
      echocardiography, exercise test and SLE disease activity index (SLEDAI) were
      recorded. Twenty patients were excluded on the basis of our exclusion criteria.
      The patients were divided to two groups based on SLEDAI: 54 in the high-score
      group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).QT dispersion was
      significantly higher in high-score group (58.31 +/- 18.66 vs. 47.90 +/- 17.41
      respectively; P < 0.004). QT dispersion was not significantly higher in patients
      who had received hydroxychloroquine (54.17 +/- 19.36 vs. 50.82 +/- 15.96, P =
      0.45) or corticosteroids (53.58 +/- 19.16 vs. 50.40 + 11.59, P = 0.47). There was
      a statistically significant correlation between abnormal echocardiographic
      findings (abnormalities of pericardial effusion, pericarditis, pulmonary
      hypertension and Libman-Sacks endocarditis) and SLEADI (P < 0.004). CONCLUSIONS:
      QT dispersion can be a useful, simple noninvasive method for the early detection
      of cardiac involvement in SLE patients with active disease. Concerning high
      chance of cardiac involvement, cardiovascular evaluation for every SLE patient
      with a SLEDAI higher than 10 may be recommended. TRIAL REGISTRATION:
      Clinicaltrial.gov registration NCT01031797.

PMID- 22369271
TI  - Direct and contextual effects of individual values on organizational citizenship
      behavior in teams.
AB  - The authors use Schwartz's values theory as an integrative framework for testing
      the relationship between individual values and peer-reported organizational
      citizenship behavior (OCB) in teams, controlling for sex, satisfaction, and
      personality traits. Using hierarchical linear modeling in a sample of 582
      students distributed across 135 class project teams, the authors find positive,
      direct effects for achievement on citizenship behaviors directed toward
      individuals (OCB-I), for benevolence on citizenship behaviors directed toward the
      group (OCB-O), and for self-direction on both OCB-I and OCB-O. Applying
      relational demography techniques to test for contextual effects, the authors find
      that group mean power scores negatively moderate the relationship between
      individual power and OCB-I, whereas group mean self-direction scores positively
      moderate the relationship between self-direction and both OCB-I and OCB-O.

PMID- 22369272
TI  - Lost sleep and cyberloafing: Evidence from the laboratory and a daylight saving
      time quasi-experiment.
AB  - The Internet is a powerful tool that has changed the way people work. However,
      the ubiquity of the Internet has led to a new workplace threat to productivity
      cyberloafing. Building on the ego depletion model of self-regulation, we examine
      how lost and low-quality sleep influence employee cyberloafing behaviors and how
      individual differences in conscientiousness moderate these effects. We also
      demonstrate that the shift to Daylight Saving Time (DST) results in a dramatic
      increase in cyberloafing behavior at the national level. We first tested the DST
      cyberloafing relation through a national quasi-experiment, then directly tested
      the relation between sleep and cyberloafing in a closely controlled laboratory
      setting. We discuss the implications of our findings for theory, practice, and
      future research.

PMID- 22369273
TI  - Characterization of oligomeric procyanidins and identification of quercetin
      glucuronide from lotus ( Nelumbo nucifera Gaertn.) seedpod.
AB  - Procyanidins are a class of polyphenols in the plant kingdom. Lotus ( Nelumbo
      nucifera Gaertn.) seedpods, the inedible part of lotus and a byproduct during the
      production of lotus seeds, were found to be a new source rich in procyanidins.
      Detailed information about oligomeric procyanidins in lotus seedpods remains
      unknown. In this study, lotus seedpods were extracted using 60% aqueous methanol
      and characterized with phloroglucinolysis and liquid chromatography (mass
      spectrometry with an electrospray ionization source). The results indicate that
      the oligomeric and polymeric fraction had a mean degree of polymerization of 3.2
      and 15.4, respectively, and consisted of (+)-catechin (m/z 289), gallocatechin or
      epigallocatechin (m/z 305), quercetin glycoside (m/z 463), quercetin glucuronide
      (m/z 477), procyanidin dimers (m/z 577.1), proanthocyanidin dimer gallate (m/z
      593.3), prodelphinidin dimers (m/z 609.1), procyanidin trimers (m/z 865.1), etc.
      Quercetin glucuronide was further purified using flash chromatography and
      identified as quercetin-3-O-beta-glucuronide by determining its exact mass using
      ion-trap time-of-flight mass spectrometry and 1H and 13C nuclear magnetic
      resonance, 1H-detected heteronuclear single-quantum coherence, and 1H-detected
      heteronuclear multiple-bond correlation analyses.

PMID- 22369274
TI  - Ecosystem service: from virtual reality to ground truth.

PMID- 22369275
TI  - Extracting regulatory modules from gene expression data by sequential pattern
      mining.
AB  - BACKGROUND: Identifying a regulatory module (RM), a bi-set of co-regulated genes
      and co-regulating conditions (or samples), has been an important challenge in
      functional genomics and bioinformatics. Given a microarray gene-expression
      matrix, biclustering has been the most common method for extracting RMs. Among
      biclustering methods, order-preserving biclustering by a sequential pattern
      mining technique has native advantage over the conventional biclustering
      approaches since it preserves the order of genes (or conditions) according to the
      magnitude of the expression value. However, previous sequential pattern mining
      based biclustering has several weak points in that they can easily be
      computationally intractable in the real-size of microarray data and sensitive to
      inherent noise in the expression value. RESULTS: In this paper, we propose a
      novel sequential pattern mining algorithm that is scalable in the size of
      microarray data and robust with respect to noise. When applied to the microarray
      data of yeast, the proposed algorithm successfully found long order-preserving
      patterns, which are biologically significant but cannot be found in randomly
      shuffled data. The resulting patterns are well enriched to known annotations and
      are consistent with known biological knowledge. Furthermore, RMs as well as inter
      module relations were inferred from the biologically significant patterns.
      CONCLUSIONS: Our approach for identifying RMs could be valuable for
      systematically revealing the mechanism of gene regulation at a genome-wide level.

PMID- 22369278
TI  - Range-edge genetic diversity: locally poor extant southern patches maintain a
      regionally diverse hotspot in the seagrass Zostera marina.
AB  - Refugial populations at the rear edge are predicted to contain higher genetic
      diversity than those resulting from expansion, such as in post-glacial
      recolonizations. However, peripheral populations are also predicted to have
      decreased diversity compared to the centre of a species' distribution. We aim to
      test these predictions by comparing genetic diversity in populations at the
      limits of distribution of the seagrass Zostera marina, with populations in the
      species' previously described central diversity 'hotspot'. Zostera marina
      populations show decreased allelic richness, heterozygosity and genotypic
      richness in both the 'rear' edge and the 'leading' edge compared to the diversity
      'hotspot' in the North Sea/Baltic region. However, when populations are pooled,
      genetic diversity at the southern range is as high as in the North Sea/Baltic
      region while the 'leading edge' remains low in genetic diversity. The decreased
      genetic diversity in these southern Iberian populations compared to more central
      populations is possibly the effect of drift because of small effective population
      size, as a result of reduced habitat, low sexual reproduction and low gene flow.
      However, when considering the whole southern edge of distribution rather than per
      population, diversity is as high as in the central 'hotspot' in the North
      Sea/Baltic region. We conclude that diversity patterns assessed per population
      can mask the real regional richness that is typical of rear edge populations,
      which have played a key role in the species biogeographical history and as
      marginal diversity hotspots have very high conservation value.

PMID- 22369276
TI  - Absolute lymphocyte count is associated with survival in ovarian cancer
      independent of tumor-infiltrating lymphocytes.
AB  - BACKGROUND: The immune system strongly influences outcome in patients with
      ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood
      (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been
      associated with favourable prognosis. However, the mechanistic relationships
      between ALC, TIL and prognosis are poorly understood. We hypothesized that high
      ALC values might be associated with stronger tumor immunity as manifested by
      increased TIL, decreased tumor burden and longer survival. METHODS: ALC values
      were collected from patient records >= 2 years before, during or after primary
      treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were
      assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed
      by immunohistochemistry. RESULTS: Overall, patients had normal ALC values two or
      more years prior to diagnosis of HGSC. These values were not predictive of
      disease severity or survival upon subsequent development of HGSC. Rather, ALC
      declined upon development of HGSC in proportion to disease burden. This decline
      involved all lymphocyte subsets. ALC increased following surgery, remained stable
      during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values
      recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were
      associated with progression-free survival. CONCLUSIONS: Patients with high
      intrinsic ALC values show no clinical or survival advantage upon subsequent
      development of HGSC. ALC values at diagnosis are prognostic due to an association
      with disease burden rather than TIL. Therapeutic enhancement of ALC may be
      necessary but not sufficient to improve survival in HGSC.

PMID- 22369279
TI  - Clinical application of 2.7M Cytogenetics array for CNV detection in subjects
      with idiopathic autism and/or intellectual disability.
AB  - Higher resolution whole-genome arrays facilitate the identification of smaller
      copy number variations (CNVs) and their integral genes contributing to autism
      and/or intellectual disability (ASD/ID). Our study describes the use of one of
      the highest resolution arrays, the Affymetrix((r)) Cytogenetics 2.7M array,
      coupled with quantitative multiplex polymerase chain reaction (PCR) of short
      fluorescent fragments (QMPSF) for detection and validation of small CNVs. We
      studied 82 subjects with ASD and ID in total (30 in the validation and 52 in the
      application cohort) and detected putatively pathogenic CNVs in 6/52 cases from
      the application cohort. This included a 130-kb maternal duplication spanning
      exons 64-79 of the DMD gene which was found in a 3-year-old boy manifesting
      autism and mild neuromotor delays. Other pathogenic CNVs involved 4p14, 12q24.31,
      14q32.31, 15q13.2-13.3, and 17p13.3. We established the optimal experimental
      conditions which, when applied to select small CNVs for QMPSF confirmation,
      reduced the false positive rate from 60% to 25%. Our work suggests that selection
      of small CNVs based on the function of integral genes, followed by review of
      array experimental parameters resulting in highest confirmation rate using
      multiplex PCR, may enhance the usefulness of higher resolution platforms for ASD
      and ID gene discovery.

PMID- 22369280
TI  - Numerical-analytic implementation of the higher-order canonical Van Vleck
      perturbation theory for the interpretation of medium-sized molecule vibrational
      spectra.
AB  - Anharmonic vibrational states of semirigid polyatomic molecules are often studied
      using the second-order vibrational perturbation theory (VPT2). For efficient
      higher-order analysis, an approach based on the canonical Van Vleck perturbation
      theory (CVPT), the Watson Hamiltonian and operators of creation and annihilation
      of vibrational quanta is employed. This method allows analysis of the convergence
      of perturbation theory and solves a number of theoretical problems of VPT2, e.g.,
      yields anharmonic constants y(ijk), z(ijkl), and allows the reliable evaluation
      of vibrational IR and Raman anharmonic intensities in the presence of resonances.
      Darling-Dennison and higher-order resonance coupling coefficients can be reliably
      evaluated as well. The method is illustrated on classic molecules: water and
      formaldehyde. A number of theoretical conclusions results, including the
      necessity of using sextic force field in the fourth order (CVPT4) and the nearly
      vanishing CVPT4 contributions for bending and wagging modes. The coefficients of
      perturbative Dunham-type Hamiltonians in high-orders of CVPT are found to conform
      to the rules of equality at different orders as earlier proven analytically for
      diatomic molecules. The method can serve as a good substitution of the more
      traditional VPT2.

PMID- 22369281
TI  - White fingernails associated with anaemia.

PMID- 22369282
TI  - Incorporation of ring nitrogens into diphenylamine antioxidants: striking a
      balance between reactivity and stability.
AB  - The incorporation of nitrogen atoms into the aryl rings of conventional
      diphenylamine antioxidants enables the preparation of readily accessible, air
      stable analogues, several of which have temperature-independent radical-trapping
      activities up to 200-fold greater than those of typical commercial
      diphenylamines. Amazingly, the nitrogen atoms raise the oxidation potentials of
      the amines without greatly changing their radical-trapping (H-atom transfer)
      reactivity.

PMID- 22369283
TI  - Bone marrow stem cells-derived microvesicles protect against renal injury in the
      mouse remnant kidney model.
AB  - AIMS:   Several studies have demonstrated administration of mesenchymal stem
      cells (MSC) could reverse kidney injury by paracrine mechanisms rather than by
      MSC transdifferentiation. Recently, a few researchers found microvesicles (MV)
      derived from MSC might be a paracrine mechanism for cell-to-cell communication.
      The aim of this study was to investigate the repair effects of MV in a 5/6
      subtotal nephrectomy (Nx) mice model. METHODS:   The animals were randomly
      divided into four groups: Control, Nx, Nx + MSC and Nx + MV group. MSC were
      injected (1 * 10(6) /mouse) through caudal vein in Nx + MSC group at the second
      day after the surgery and MV were injected (30 ug/mouse) through caudal vein in
      Nx + MV group on alternate days. Mice were killed on day 7 after the first time
      of administration. Blood urea nitrogen (BUN), serum creatinine (Scr), uric acid
      (UA) and proteinuria were evaluated. Histopathology of kidney was analysed.
      RESULTS:   In Nx mice, the levels of Scr, UA and proteinuria were significantly
      decreased with administration of MV and MSC (P < 0.05). The remnant kidneys of MV
      and MSC-treated Nx mice showed less fibrosis, interstitial lymphocyte infiltrates
      and less or absent tubular atrophy compared with the untreated Nx group. The
      Histological Score of Kidney in untreated mice was 3.13 +/- 0.74, while in the
      MSC-treated group it was 1.67 +/- 0.47 and in the MV-treated group it was 1.80 +/
      0.44, nearly preserving normal morphology of the kidney (P < 0.01). CONCLUSION: 
      This study showed MV protects against renal injury induced by 5/6 Nx, which
      could mimic the role of MSC in kidney repair. The research showed a newly
      potential therapeutic approach to kidney diseases.

PMID- 22369284
TI  - Rituximab  for chronic lymphocytic leukemia.
AB  - INTRODUCTION: Rituximab is a high-affinity chimeric mouse anti-CD20 monoclonal
      antibody, currently used for the treatment of non-Hodgkin's lymphoma (NHL),
      chronic lymphocytic leukemia (CLL) and autoimmune disorders. AREAS COVERED: This
      article summarizes recent achievements in the clinical activity and toxicity of
      rituximab in the treatment of patients with CLL. A literature search was
      conducted of the PubMed MEDLINE database for articles in English. Publications
      from 2000 through January 2012 were scrutinized. The search terms used were
      rituximab in conjunction with chronic lymphocytic leukemia or CLL. Conference
      proceedings from the previous 5 years of The American Society of Hematology, The
      European Hematology Association, and American Society of Clinical Oncology were
      searched manually. Additional relevant publications were obtained by reviewing
      the references from the chosen articles. EXPERT OPINION: Rituximab is an active
      drug in CLL when used as a single agent and in combination with chemotherapy,
      particulary with fludarabine or fludarabine and cyclophosphamide (R-FC regimen).
      In addition, rituximab may be an optimal therapeutic choice of treatment for CLL
      associated autoimmune cytopenias.

PMID- 22369286
TI  - Systemic immune cell response in rats after pulmonary exposure to manganese
      containing particles collected from welding aerosols.
AB  - Welding fume inhalation affects the immune system of exposed workers. Manganese
      (Mn) in welding fume may induce immunosuppressive effects. The goal was to
      determine if Mn in welding fume alters immunity by reducing the number of
      circulating total leukocytes and specific leukocyte sub-populations. Sprague
      Dawley rats were treated by intratracheal instillation (ITI) with either a single
      dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with
      welding fumes that contained different levels of Mn. Additional rats were treated
      by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl2).
      Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole
      blood was recovered, and the number of circulating total leukocytes, as well as
      specific lymphocyte subsets, was determined by flow cytometry. The welding fume
      highest in Mn content significantly increased lung inflammation, injury, and
      production of inflammatory cytokines and chemokines compared to all other
      treatment groups. In addition, the same group expressed significant decreases in
      the number of circulating CD4+ and CD8+ T-lymphocytes after a single exposure,
      and significant reductions in the number of circulating total lymphocytes,
      primarily CD4+ and CD8+ T-lymphocytes, after repeated exposures (compared to
      control values). Repeated MnCl2 exposure led to a trend of a reduction (but not
      statistically significant) in circulating total lymphocytes, attributable to the
      changes in the CD4+ T-lymphocyte population levels. The welding fume with the
      lower concentration of Mn had no significant effect on the numbers of blood
      lymphocytes and lymphocyte subsets compared to control values. Evidence from this
      study indicates that pulmonary exposure to certain welding fumes cause decrements
      in systemic immune cell populations, specifically circulating T-lymphocytes, and
      these alterations in immune cell number are not dependent exclusively on Mn, but
      likely a combination of other metals present in welding fume.

PMID- 22369287
TI  - Efficacy and tolerability of vildagliptin as add-on therapy to metformin in
      Chinese patients with type 2 diabetes mellitus.
AB  - AIM: To investigate the efficacy and tolerability of vildagliptin as add-on
      therapy to metformin in Chinese patients with type 2 diabetes mellitus (T2DM)
      inadequately controlled with metformin. METHODS: This was a 24-week, randomized,
      double-blind, placebo-controlled study. Patients with T2DM (N = 438) with
      haemoglobin A1c (HbA1c) of 7.0-10.0% and fasting plasma glucose (FPG) <15 mmol/l
      (<270 mg/dl) were randomized (1 : 1 : 1) to vildagliptin 50 mg bid, vildagliptin
      50 mg qd or placebo in addition to metformin. RESULTS: The treatment groups were
      well balanced at baseline [mean HbA1c, 8.0%, FPG, 8.8 mmol/l (158 mg/dl); body
      mass index, 25.5 kg/m(2) ]. The adjusted mean change (AMDelta) in HbA1c at
      endpoint was -1.05 +/- 0.08%, -0.92 +/- 0.08% and -0.54 +/- 0.08% in patients
      receiving vildagliptin 50 mg bid, 50 mg qd and placebo, respectively. The between
      treatment difference (vildagliptin 50 mg bid-placebo) was -0.51 +/- 0.11%, p <
      0.001. A greater proportion of vildagliptin-treated patients met at least one
      responder criterion (82.1 and 70.7%) compared to placebo-treated patients
      (60.4%). The AMDelta at endpoint for FPG with vildagliptin 50 mg bid, -0.95
      mmol/l (-17.1 mg/dl); 50 mg qd, -0.84 mmol/l (-15.1 mg/dl) was significantly
      different compared with the placebo -0.26 mmol/l (-4.68 mg/dl) (p <= 0.001).
      Adverse events (AEs) were reported as 34.2, 36.5 and 37.5% for patients receiving
      vildagliptin 50 mg bid, 50 mg qd or placebo, respectively. Two patients in the
      vildagliptin 50 mg qd and one in the placebo group reported serious AEs, which
      were not considered to be related to the study drug; one incidence of
      hypoglycaemic event was reported in the vildagliptin 50 mg bid group. CONCLUSION:
      Vildagliptin as add-on therapy to metformin improved glycaemic control and was
      well tolerated in Chinese patients who were inadequately controlled by metformin
      only.

PMID- 22369288
TI  - A new fluorescent staining method for callose of microspore mother cells during
      meiosis.
AB  - To observe the dynamic behavior of callose of microspore mother cells during
      meiosis, we developed a convenient, rapid and efficient staining method using an
      improved carbol fuchsin/aniline blue solution. The stained microspore mother
      cells during meiosis showed yellowish green callose, red cytoplasm and dark red
      chromosomes when excited with blue light, which produced a contrasting image with
      a three-dimensional effect. When stained with only improved carbol fuchsin
      solution, the cells had red cytoplasm and chromosomes when excited with green
      light. The improved carbol fuchsin solution can be used to replace other more
      expensive DNA-specific dyes, such as DAPI and H33258, to reduce experimental
      costs.

PMID- 22369289
TI  - Effects of carboxylate anions on the molecular organization of H2O as probed by 1
      propanol.
AB  - We characterized the effects of carboxylate anions, formate (OFm(-)), acetate
      (OAc(-)), and propionate (OPr(-)), on the molecular organization of liquid H(2)O
      by the 1-propanol (1P) probing methodology. The latter thermodynamic methodology
      provides two indices: one pertaining to the hydration number, n(H), and the other
      being related to the net increase/decrease of the entropy-volume cross
      fluctuation of the system. The results indicated that OFm(-) is a hydration
      center with n(H) = 1.2 +/- 0.5 and leaves the bulk H(2)O away from the hydration
      shell unperturbed. We suggest that this single H(2)O hydrates preferentially one
      of the O's in the COO(-) group, showing the hydration center character. The
      values of n(H) for OAc(-) and OPr(-) were found to be 3.7 +/- 0.8 and 9 +/- 2,
      respectively, out of which one H(2)O molecule is used for hydrating the COO(-)
      side and the remaining 2.7 and 8 H(2)O molecules hydrate the respective alkyl
      group. Hence, OPr(-) is more hydrophobic than OAc(-) in terms of the hydration
      number. However, both alkyl moieties seem to equally retard the hydrogen bond
      probability of bulk H(2)O away from hydration shells around nonpolar sites, as
      much as the probing 1P does.

PMID- 22369290
TI  - The Tenth Asia Pacific Bioinformatics Conference (APBC 2012). Introduction.

PMID- 22369291
TI  - Should policy-makers and managers trust PSI? An empirical validation study of
      five patient safety indicators in a national health service.
AB  - BACKGROUND: Patient Safety Indicators (PSI) are being modestly used in Spain,
      somewhat due to concerns on their empirical properties. This paper provides
      evidence by answering three questions: a) Are PSI differences across hospitals
      systematic -rather than random?; b) Do PSI measure differences among hospital
      providers -as opposed to differences among patients?; and, c) Are measurements
      able to detect hospitals with a higher than "expected" number of cases? METHODS:
      An empirical validation study on administrative data was carried out. All 2005
      and 2006 publicly-funded hospital discharges were used to retrieve eligible cases
      of five PSI: Death in low-mortality DRGs (MLM); decubitus ulcer (DU);
      postoperative pulmonary embolism or deep-vein thrombosis (PE-DVT); catheter
      related infections (CRI), and postoperative sepsis (PS). Empirical Bayes
      statistic (EB) was used to estimate whether the variation was systematic;
      logistic-multilevel modelling determined what proportion of the variation was
      explained by the hospital; and, shrunken residuals, as provided by multilevel
      modelling, were plotted to flag hospitals performing worse than expected.
      RESULTS: Variation across hospitals was observed to be systematic in all
      indicators, with EB values ranging from 0.19 (CI95%:0.12 to 0.28) in PE-DVT to
      0.34 (CI95%:0.25 to 0.45) in DU. A significant proportion of the variance was
      explained by the hospital, once patient case-mix was adjusted: from a 6% in MLM
      (CI95%:3% to 11%) to a 24% (CI95%:20% to 30%) in CRI. All PSI were able to flag
      hospitals with rates over the expected, although this capacity decreased when the
      largest hospitals were analysed. CONCLUSION: Five PSI showed reasonable empirical
      properties to screen healthcare performance in Spanish hospitals, particularly in
      the largest ones.

PMID- 22369292
TI  - In silico labeling reveals the time-dependent label half-life and transit-time in
      dynamical systems.
AB  - BACKGROUND: Mathematical models of dynamical systems facilitate the computation
      of characteristic properties that are not accessible experimentally. In cell
      biology, two main properties of interest are (1) the time-period a protein is
      accessible to other molecules in a certain state - its half-life - and (2) the
      time it spends when passing through a subsystem - its transit-time. We discuss
      two approaches to quantify the half-life, present the novel method of in silico
      labeling, and introduce the label half-life and label transit-time. The developed
      method has been motivated by laboratory tracer experiments. To investigate the
      kinetic properties and behavior of a substance of interest, we computationally
      label this species in order to track it throughout its life cycle. The
      corresponding mathematical model is extended by an additional set of reactions
      for the labeled species, avoiding any double-counting within closed circuits,
      correcting for the influences of upstream fluxes, and taking into account
      combinatorial multiplicity for complexes or reactions with several reactants or
      products. A profile likelihood approach is used to estimate confidence intervals
      on the label half-life and transit-time. RESULTS: Application to the JAK-STAT
      signaling pathway in Epo-stimulated BaF3-EpoR cells enabled the calculation of
      the time-dependent label half-life and transit-time of STAT species. The results
      were robust against parameter uncertainties. CONCLUSIONS: Our approach renders
      possible the estimation of species and label half-lives and transit-times. It is
      applicable to large non-linear systems and an implementation is provided within
      the PottersWheel modeling framework (http://www.potterswheel.de).

PMID- 22369294
TI  - ApicoAlign: an alignment and sequence search tool for apicomplexan proteins.
AB  - BACKGROUND: Over the recent years, a number of genomes have been successfully
      sequenced and this was followed by genome annotation projects to help understand
      the biological capabilities of newly sequenced genomes. To improve the annotation
      of Plasmodium falciparum proteins, we earlier developed parasite specific
      matrices (PfSSM) and demonstrated their (Smat80 and PfFSmat60) better performance
      over standard matrices (BLOSUM and PAM). Here we extend that study to nine
      apicomplexan species other than P. falciparum and develop a web application
      ApicoAlign for improving the annotation of apicomplexan proteins. RESULTS: The
      SMAT80 and PfFSmat60 matrices perform better for apicomplexan proteins compared
      to BLOSUM in detecting the orthologs and improving the alignment of these
      proteins with their potential orthologs respectively. Database searches against
      non-redundant (nr) database have shown that SMAT80 gives superior performance
      compared to BLOSUM series in terms of E-values, bit scores, percent identity,
      alignment length and mismatches for most of the apicomplexan proteins studied
      here. Using these matrices, we were able to find orthologs for rhomboid proteases
      of P. berghei, P. falciparum & P. vivax and large subunit of U2 snRNP auxiliary
      factor of Cryptosporidium parvum in Arabidopsis thaliana. We also show improved
      pairwise alignments of proteins from Apicomplexa viz. Cryptosporidium parvum and
      P. falciparum with their orthologs from other species using the PfFSmat60 matrix.
      CONCLUSIONS: The SMAT80 and PfFSmat60 substitution matrices perform better for
      apicomplexan proteins compared to BLOSUM series. Since they can be helpful in
      improving the annotation of apicomplexan genomes and their functional
      characterization, we have developed a web server ApicoAlign for finding orthologs
      and aligning apicomplexan proteins.

PMID- 22369295
TI  - Improvement in the prediction of the translation initiation site through
      balancing methods, inclusion of acquired knowledge and addition of features to
      sequences of mRNA.
AB  - BACKGROUND: The accurate prediction of the initiation of translation in sequences
      of mRNA is an important activity for genome annotation. However, obtaining an
      accurate prediction is not always a simple task and can be modeled as a problem
      of classification between positive sequences (protein codifiers) and negative
      sequences (non-codifiers). The problem is highly imbalanced because each molecule
      of mRNA has a unique translation initiation site and various others that are not
      initiators. Therefore, this study focuses on the problem from the perspective of
      balancing classes and we present an undersampling balancing method, M-clus, which
      is based on clustering. The method also adds features to sequences and improves
      the performance of the classifier through the inclusion of knowledge obtained by
      the model, called InAKnow. RESULTS: Through this methodology, the measures of
      performance used (accuracy, sensitivity, specificity and adjusted accuracy) are
      greater than 93% for the Mus musculus and Rattus norvegicus organisms, and varied
      between 72.97% and 97.43% for the other organisms evaluated: Arabidopsis
      thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Nasonia
      vitripennis. The precision increases significantly by 39% and 22.9% for Mus
      musculus and Rattus norvegicus, respectively, when the knowledge obtained by the
      model is included. For the other organisms, the precision increases by between
      37.10% and 59.49%. The inclusion of certain features during training, for
      example, the presence of ATG in the upstream region of the Translation Initiation
      Site, improves the rate of sensitivity by approximately 7%. Using the M-Clus
      balancing method generates a significant increase in the rate of sensitivity from
      51.39% to 91.55% (Mus musculus) and from 47.45% to 88.09% (Rattus norvegicus).
      CONCLUSIONS: In order to solve the problem of TIS prediction, the results
      indicate that the methodology proposed in this work is adequate, particularly
      when using the concept of acquired knowledge which increased the accuracy in all
      databases evaluated.

PMID- 22369297
TI  - Anthracosis in Iran, un-answered questions.

PMID- 22369296
TI  - Expression profile of small RNAs in Acacia mangium secondary xylem tissue with
      contrasting lignin content - potential regulatory sequences in monolignol
      biosynthetic pathway.
AB  - BACKGROUND: Lignin, after cellulose, is the second most abundant biopolymer
      accounting for approximately 15-35% of the dry weight of wood. As an important
      component during wood formation, lignin is indispensable for plant structure and
      defense. However, it is an undesirable component in the pulp and paper industry.
      Removal of lignin from cellulose is costly and environmentally hazardous process.
      Tremendous efforts have been devoted to understand the role of enzymes and genes
      in controlling the amount and composition of lignin to be deposited in the cell
      wall. However, studies on the impact of downregulation and overexpression of
      monolignol biosynthesis genes in model species on lignin content, plant fitness
      and viability have been inconsistent. Recently, non-coding RNAs have been
      discovered to play an important role in regulating the entire monolignol
      biosynthesis pathway. As small RNAs have critical functions in various biological
      process during wood formation, small RNA profiling is an important tool for the
      identification of complete set of differentially expressed small RNAs between low
      lignin and high lignin secondary xylem. RESULTS: In line with this, we have
      generated two small RNAs libraries from samples with contrasting lignin content
      using Illumina GAII sequencer. About 10 million sequence reads were obtained in
      secondary xylem of Am48 with high lignin content (41%) and a corresponding 14
      million sequence reads were obtained in secondary xylem of Am54 with low lignin
      content (21%). Our results suggested that A. mangium small RNAs are composed of a
      set of 12 highly conserved miRNAs families found in plant miRNAs database, 82
      novel miRNAs and a large proportion of non-conserved small RNAs with low
      expression levels. The predicted target genes of those differentially expressed
      conserved and non-conserved miRNAs include transcription factors associated with
      regulation of the lignin biosynthetic pathway genes. Some of these small RNAs
      play an important role in epigenetic silencing. Differential expression of the
      small RNAs between secondary xylem tissues with contrasting lignin content
      suggests that a cascade of miRNAs play an interconnected role in regulating the
      lignin biosynthetic pathway in Acacia species. CONCLUSIONS: Our study critically
      demonstrated the roles of small RNAs during secondary wall formation. Comparison
      of the expression pattern of small RNAs between secondary xylem tissues with
      contrasting lignin content strongly indicated that small RNAs play a key
      regulatory role during lignin biosynthesis. Our analyses suggest an evolutionary
      mechanism for miRNA targets on the basis of the length of their 5' and 3' UTRs
      and their cellular roles. The results obtained can be used to better understand
      the roles of small RNAs during lignin biosynthesis and for the development of
      gene constructs for silencing of specific genes involved in monolignol
      biosynthesis with minimal effect on plant fitness and viability. For the first
      time, small RNAs were proven to play an important regulatory role during lignin
      biosynthesis in A. mangium.

PMID- 22369298
TI  - Prevalence of tuberculosis in patients with anthracosis: study on 150 subjects.
AB  - BACKGROUND: A probable concordance and association between pulmonary tuberculosis
      and anthracosis was observed in the published literature. We conducted this study
      to evaluate the clinical and radiologic characteristics of patients with
      bronchoscopic evidence of anthracosis as well as the prevalence of pulmonary
      tuberculosis in patients with anthracosis. METHODS: Included in the study were
      150 consecutive patients with evidence of anthracosis as evidenced by
      bronchoscopy. Pulmonary tuberculosis diagnostic work up which included
      bronchoalveolar lavage, sputum smears and cultures, or histologic examination of
      lung biopsies was performed on all patients. Patients' clinical, pathological,
      and radiological findings were also recorded and analyzed. RESULTS: A total of 88
      men and 62 women, ranging in age from 42 to 92 years were included in the study.
      Dyspnea (38.7%) and productive cough (35.3%) were among the most common chief
      complaints. The abnormal bronchoscopic findings were seen most frequently in the
      right middle lobe bronchus. In 42 patients pulmonary tuberculosis was confirmed
      either bacteriologically (n = 32) or histologically (n = 10). CT scans of 26
      patients were examined, of which the most frequent findings were consolidation
      and a reticular pattern. Pleural involvement was observed in 14 patients.
      CONCLUSION: Prevalence of pulmonary tuberculosis was higher among those with
      bronchial stenosis (P < 0.05). These findings have suggested that bronchial
      anthracosis, especially cases of localized anthracosis, in patients with
      bronchial stenosis and in those without a history of smoking or occupational
      exposure may be caused by tuberculosis.

PMID- 22369299
TI  - A cross-sectional study on food patterns and adiposity among individuals with
      abnormal glucose homeostasis.
AB  - BACKGROUND: Dietary habits play an important role in the prevention of chronic
      disease; however, few studies have assessed the major dietary patterns in Middle
      Eastern countries. This study identifies major dietary patterns among Iranian
      people with abnormal glucose homeostasis. METHODS: This cross-sectional study was
      conducted at the Diabetes Research Center, Isfahan, Iran among 425 subjects with
      abnormal glucose homeostasis. Patients were of ages 35 - 55 years and had family
      histories of diabetes. We assessed dietary intake by the use of a food frequency
      questionnaire (FFQ) that contained 39 food items. General obesity was defined as
      a BMI >= 30 kg/m2 and central obesity was defined as waist circumference (WC) >=
      88 in women and WC >= 102 in men. RESULTS: Five major dietary patterns were
      revealed by factor analysis: 'western', 'healthy', 'vegetarian', 'high-fat
      dairy', and 'chicken and plants'. Those in the top tertile of the 'western
      pattern' had greater odds for general (OR = 1.73; 95% CI = 1.07 - 2.78) and
      central obesity (OR = 2, 95% CI = 1.24 - 3.22), however these associations were
      not significant after adjustment for confounding variables. The 'high-fat dairy
      pattern' was associated with greater odds of general obesity only after adjusting
      for confounding variables (OR = 1.73; 95%CI = 1.01 - 2.96). CONCLUSION: The
      dietary pattern characterized by high intake of hydrogenated fat and sugar was
      shown to be positively associated with a risk of general and central obesity,
      however further prospective studies are required to confirm our findings.

PMID- 22369300
TI  - Evaluation of current guthrie TSH cut-off point in Iran congenital hypothyroidism
      screening program: a cost-effectiveness analysis.
AB  - BACKGROUND: The threshold of thyroid-stimulating hormone (TSH) in current
      screening for congenital hypothyroidism (CH) from the heel prick test is 5 mU/l.
      This study uses cost-effective analysis to evaluate increasing the threshold to
      minimize false-positive results and recall rates. METHODS: Cost of screening,
      diagnosis and treatment, education, and care of mentally retarded patients were
      gathered from the Ministry of Health State Welfare Organization and Department of
      Education in Tehran. Screening data were obtained from 34,007 neonates in the
      Central Health Laboratory of Tehran University of Medical Sciences in 2009.
      Sensitivity analysis and calculation of confidence interval for incremental costs
      and effects (gained disability adjusted life years - DALYs) and incremental cost
      effectiveness ratios (ICER) were performed by Monte Carlo simulation with Ersatz
      software. RESULTS: ICER for screening programs with different TSH cut-off points
      versus no screening was similar, and approximately -4.5 +/- 0.2 thousand US
      dollars per gained DALY. In the proposed cohort (10,000 neonates), gained DALYs
      were 316 +/- 50 for a cut off point of 5 mU/l, 251 +/- 40 for 10 mU/l, 146 +/- 23
      for 15 mU/l, and 113 +/- 18 for a cut-off point of 20 mU/l. Sensitivity analysis
      showed that the model remained the same when the input parameters were changed.
      CONCLUSION: This study demonstrates that the current threshold of TSH in the
      national CH screening program in terms of cost-effectiveness is the most
      appropriate threshold. However, more studies are needed to examine new strategies
      and methods to reduce recall rates and related consequences such as repeated
      thyroid testing in neonates.

PMID- 22369301
TI  - Prevalence of oral lesions and normal variants of the oral mucosa in 12 to 15
      year-old students in Tehran, Iran.
AB  - OBJECTIVES: There are relatively few systematic studies, documenting the
      prevalence of mucosal disorders in children and adolescents. The purpose of this
      study was to determine the prevalence of oral lesions in 12- to 15-year olds
      living in Tehran and to assess the possible relationship between the occurrence
      of these lesions and gender. METHODS: A cross-sectional study was designed in
      which 1020 adolescents were participated. The sample size was based upon an
      expected oral lesion prevalence of 25%, a precision of 0.05 and a confidence
      level of 99. Epi-info version 6.0 was used for statistical analysis. RESULTS: Two
      hundred eighty-six adolescents (28.0%) were diagnosed with at least one oral
      mucosal lesion at the time of the examination. The prevalence of any oral mucosal
      lesion was 29.2% among the boys and 26.9% among the girls. With the exception of
      melanotic macules, there were no statistically significant differences in oral
      mucosal lesion prevalence by gender. CONCLUSION: More than 28% of the adolescents
      were found to have at least one oral mucosal lesion. Melanotic macule was found
      to be proportionally more common in boys than girls.

PMID- 22369302
TI  - The expression of CXCR3 and CD30 in mycosis fungoides.
AB  - BACKGROUND: The clinical progression of mycosis fungoides (MF) often correlates
      with microscopic large cell transformation (LCT). It is reported that CD30
      expression in the LCT of MF is associated with an absence of CXCR3 expression.
      This study investigates a large number of patients diagnosed with MF to determine
      the correlation between expression of CXCR3 and CD30 in additional sections.
      METHODS: The study included archival skin specimens from 101 patients with MF. We
      analyzed these specimens by immunohistochemistry for expressions of CXCR3 and
      CD30. RESULTS: The biopsy specimens showed microscopic features of low grade MF
      (LG-MF) in 80 cases and transformed MF (T-MF) in 21 cases. Tumor lymphocytes
      expressed CXCR3 in 61 out of 80 cases (76.3%) of LG-MF and in 10 out of 21 cases
      (47.6%) of T-MF.  CD30 positivity (CD30+) was seen in 16 of 80 cases (20%) of LG
      MF and 12 of 21 cases (57.1%) of T-MF. The tumor cells in 8 of the 12 CD30+ T-MF
      cases showed scattered expression of CXCR3. CONCLUSION: CXCR3 expression was
      associated with epidermotropic T cell tumors but was greatly absent in dermal
      ones. Scattered or diffuse CD30 expression in T-MF was not associated with an
      absence of CXCR3 expression.

PMID- 22369303
TI  - Genetic polymorphism of Leishmania major in two hyper endemic regions of Iran
      revealed by PPIP-PCR and ITS- RFLP.
AB  - BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is a polymorphic disease that
      may show various clinical manifestations. Although it is suggested that the
      genetic variability of the parasite is one of the factors influencing clinical
      manifestations of leishmaniasis, no data exists regarding genetic polymorphism of
      Leishmania major (L.major). This study investigates the determination of genetic
      variations within the species of L.major isolates from different cases of ZCL in
      two hyper-endemic areas of Iran. METHODS: A variety of nucleic acid detection
      methods that target both DNA and RNA have been developed. Among these, the
      polymerase chain reaction (PCR) method proved to be a highly sensitive and
      specific technique. Species identification was based on permissively primed
      intergenic polymorphic-polymerase chain reaction (PPIP-PCR) and restriction
      fragment length polymorphism analysis of amplified internal transcribed spacer
      (ITS-RFLP) in the ribosomal operon of L.major from clinically different forms of
      ZCL. The DNA products were amplified by PCR, followed by digestion of the PCR
      product with restriction enzymes. The profiles were visualized in agarose gel
      under ultraviolet (UV) light. RESULTS: The PCR product obtained for all isolates
      was about 1060 bp in size. Different patterns of PPIP-PCR and ITS-RFLP in the
      ribosomal operon were classified as I, II, III, IV, and V. This classification
      was according to the number and localization of bands. Results of this research
      detected the genetic and clinical polymorphism of L. major, and showed that
      strain A was more frequent than other strains. CONCLUSION: The L.major causing
      ZCL in Isfahan, Iran is genetically a highly polymorphic species and PPIP-PCR
      exposed more genetic polymorphism among clinical samples in Isfahan, Iran.

PMID- 22369304
TI  - Endoscopic cyanoacrylate injection for the treatment of bleeding gastric varices:
      the first Iranian series.
AB  - BACKGROUND: Gastric varices are a major cause of gastrointestinal bleeding and
      death in patients with portal hypertension. N-butyl-2-cyanoacrylate injection is
      a new method for controlling bleeding gastric varices. This study aims to
      investigate the prognosis and complications of cyanoacrylate therapy for bleeding
      gastric varices. METHODS: We conducted a prospective study between May 2009 and
      January 2010 at our center affiliated with the Shiraz University of Medical
      Sciences, Shiraz, Iran. All patients with gastric variceal bleeding were enrolled
      in the study. N-butyl-2-cyanoacrylate injection was performed for treatment of
      the bleeding, and patients underwent monthly endoscopies to determine the
      outcomes. RESULTS: There were 13 patients with portal hypertension and gastric
      variceal bleeding included in the study. Initial hemostasis was obtained in all
      patients but more than one injection was needed in seven patients. Two patients
      developed re-bleeding and two died of advanced cirrhosis and other accompanying
      diseases.  CONCLUSION: No major complications were observed after treatment with
      N-butyl-2-cyanoacrylate. This method can be safely used in treatment of gastric
      variceal bleeding.

PMID- 22369305
TI  - Prediction of fetal anemia by different thresholds of MCA-PSV and Delta-OD in
      first and second intrauterine transfusions.
AB  - BACKGROUND: Our aim was to compare different thresholds of middle cerebral artery
      peak systolic velocity (MCA-PSV) and amniotic fluid delta optical density (Delta
      OD) with fetal hemoglobin (Hb) during first and second intrauterine transfusions
      (IUT). METHODS: We determined serial MCA-PSV and Delta-OD in 27 red blood cell
      alloimmunized fetuses who needed IUT. Before the second IUT, MCA-PSV was
      measured. The sensitivity and specificity of MCA-PSV and Delta-OD were calculated
      and compared with fetal hemoglobin  levels. RESULTS: From 27 fetuses, first time
      IUT MCA-PSV with a normal median value (MOM) cutoff of > 1.29 detected 60% of the
      moderate and 100% of the severe anemia cases. MCA-PSV of MOM > 1.5 detected none
      of the moderate and 93% of severe anemia cases. Delta-OD detected 50% of moderate
      anemic and 80% of severe anemic cases. At the second IUT, 91% of severe anemia
      cases were confirmed by MCA-PSV with MOM > 1.5 whereas MCA-PSV with MOM > 1.29
      confirmed all cases. One case of moderate anemia was de-tected by MCA-PSV of MOM
      > 1.29 and none were detected by MCA-PSV with MOM > 1.5. CONCLUSION: Different
      thresholds of MCA-PSV have higher sensitivity and specificity for detecting
      moderate and severe fetal anemia compared with Delta-OD. It also has a high
      sensitivity at the second IUT.

PMID- 22369306
TI  - Inflammation in sporadic colorectal cancer.
AB  - Chronic inflammation plays a pivotal role in the development of colorectal cancer
      (CRC) in patients with inflammatory bowel disease (IBD). An orchestrated
      interplay of immune cells with numerous inflammatory mediators including reactive
      oxygen and nitrogen species, cyclooxygenase 2, and several cytokines promotes
      colitis-associated cancer (CAC). Recent findings have shown that inflammatory
      pathways not only are important in the development of CAC but are also involved
      in the pathogenesis of sporadic CRC. Hereby,  we review the existing experimental
      and clinical evidence that suggest a link between inflammation and tumorigenesis
      in sporadic CRC.

PMID- 22369307
TI  - The use of polymerase chain reaction assay versus cell culture in detecting
      neonatal chlamydial conjunctivitis.
AB  - One of the most common bacterial infections that causes ophthalmia neonatorum is
      Chlamydia trachomatis, (C. trachomatis). Very few studies have been performed in
      Iran using both cell culture and polymerase chain reaction (PCR) methods to
      determine the prevalence of C. trachomatis as an etiological agent of ophthalmia
      neonatorum. This study aimed to evaluate the prevalence of neonatal chlamydial
      conjunctivitis (NCC) as diagnosed by both methods in two hospitals in Tehran,
      Iran. From March 2008 to May 2009, out of 2253 neonates, 241 (10.7%) with
      clinical findings of conjunctivitis were included in this study. A total of 241
      conjunctival swabs were tested by cell culture (as the gold standard test), PCR,
      and Giemsa staining. Cell cultures were positive for C. trachomatis in 31 (12.9%)
      neonates, C. trachomatis was positive in 40 (16.6%) neonates by PCR and 18 (7.5%)
      by Giemsa staining. The sensitivity of PCR was 100%, whereas Giemsa staining
      sensitivity was 558.1%. High sensitivity (100%) and specificity (95.7%) of PCR as
      compared to culture makes it a proper diagnostic method for the detection of C.
      trachomatis.

PMID- 22369308
TI  - Direct percutaneous endoscopic jejunostomy in patients with altered anatomy.

PMID- 22369309
TI  - An incidentally swallowed toothbrush.
AB  - Although foreign body (FB) ingestion is relatively common,ingestion of a
      toothbrush is rare. We are reporting on a 26-year old female who had accidentally
      swallowed a toothbrush, which was successfully removed via endoscopy using a
      polypectomy snare.

PMID- 22369310
TI  - Photoclinic. Expiratory stridor mimicking bronchial asthma.

PMID- 22369311
TI  - A historical profile of diphtheria in Iran during the 19th and 20th centuries.
AB  - Diphtheria is a contagious and life-threatening disease historically regarded as
      a major cause of mortality, particularly in children. Over the past centuries,
      frequent diphtheria outbreaks have occurred. Herein, after a quick look at the
      history of diphtheria throughout the world, a historical account of this lethal
      disease in Iran during the 19th and 20th centuries is presented.

PMID- 22369312
TI  - The combined prognostic potential of serum high-sensitivity cardiac troponin I
      and N-terminal pro-B-type natriuretic peptide concentrations in dogs with
      degenerative mitral valve disease.
AB  - BACKGROUND: Identification of factors associated with decreased survival in dogs
      with degenerative mitral valve disease (DMVD) will allow more accurate prognosis.
      N-terminal pro-B-type natriuretic peptide (NT-proBNP) is negatively associated
      with survival in dogs with DMVD. In human patients, multimarker strategies
      provide superior risk stratification compared with single markers. HYPOTHESIS:
      High-sensitivity cardiac troponin I (hscTnI) and other clinical variables will be
      associated with survival time in dogs with DMVD. Measuring hscTnI and NT-proBNP
      in combination will be prognostically superior to measurement of either marker
      alone. The rate of change of these markers will vary according to cause of death.
      ANIMALS: Client-owned dogs (n = 202) with DMVD of varying severity and age
      matched healthy control dogs (n = 30) recruited from first opinion private
      practice. METHODS: Prospective cohort study relating clinical variables at
      enrollment in dogs with DMVD to survival time (all-cause, cardiac, and noncardiac
      mortality). Multivariable Cox regression analysis was used to identify factors
      associated with survival. Measurements were obtained approximately every 6
      months. Repeated measures models were constructed to assess changes over time.
      RESULTS: hscTnI, LVEDDN, heart rate, and age were independently associated with
      decreased survival time (all-cause mortality). Survival times were shortest in
      dogs in which both serum hscTnI and NT-proBNP were increased. hscTnI and NT
      proBNP increased more rapidly in dogs that died of cardiac disease. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Serum hscTnI has prognostic value in dogs with DMVD.
      Measurement of NT-proBNP and hscTnI is prognostically superior to measuring
      either alone. Serial measurement strategies provide additional prognostic
      information.

PMID- 22369313
TI  - Morphology control and optical properties of SiGe nanostructures grown on glass
      substrate.
AB  - With the rapid progress of nanotechnology, nanostructures with different
      morphologies have been realized, which may be very promising to enhance the
      performance of semiconductor devices. In this study, SiGe nanostructures with
      several kinds of configurations have been synthesized through a chemical vapor
      deposition process. By controlling growth conditions, different SiGe
      nanostructures can be easily tuned. Structures and compositions of the
      nanostructures were determined by scanning electron microscopy, transmission
      electron microscopy, and X-ray diffraction. The optical properties of various
      SiGe nanostructures revealed some dependence with their morphologies, which may
      be suitable for solar cell applications. The control of the SiGe morphology on
      nanoscale provides a convenient route to produce diverse SiGe nanostructures and
      creates new opportunities to realize the integration of future devices.

PMID- 22369314
TI  - OccK channels from Pseudomonas aeruginosa exhibit diverse single-channel
      electrical signatures but conserved anion selectivity.
AB  - Pseudomonas aeruginosa is a Gram-negative bacterium that utilizes substrate
      specific outer membrane (OM) proteins for the uptake of small, water-soluble
      nutrients employed in the growth and function of the cell. In this paper, we
      present for the first time a comprehensive single-channel examination of seven
      members of the OM carboxylate channel K (OccK) subfamily. Recent biochemical,
      functional, and structural characterization of the OccK proteins revealed their
      common features, such as a closely related, monomeric, 18-stranded beta-barrel
      conformation with a kidney-shaped transmembrane pore and the presence of a basic
      ladder within the channel lumen. Here, we report that the OccK proteins exhibited
      fairly distinct unitary conductance values, in a much broader range than
      previously expected, which includes low (~40-100 pS) and medium (~100-380 pS)
      conductance. These proteins showed diverse single-channel dynamics of current
      gating transitions, revealing one-open substate (OccK3), two-open substate (OccK4
      OccK6), and three-open substate (OccK1, OccK2, and OccK7) kinetics with
      functionally distinct conformations. Interestingly, we discovered that anion
      selectivity is a conserved trait among the members of the OccK subfamily,
      confirming the presence of a net pool of positively charged residues within their
      central constriction. Moreover, these results are in accord with an increased
      specificity and selectivity of these protein channels for negatively charged,
      carboxylate-containing substrates. Our findings might ignite future functional
      examinations and full atomistic computational studies for unraveling a
      mechanistic understanding of the passage of small molecules across the lumen of
      substrate-specific, beta-barrel OM proteins.

PMID- 22369315
TI  - Assessment of iron bioavailability in whole wheat bread by addition of phytase
      producing bifidobacteria.
AB  - In this study, the influence of phytase-producing  Bifidobacterium  strains
      during the breadmaking process (direct or indirect) on final bread Fe
      dialyzability and ferritin formation in Caco-2 cell as a measure of cell Fe
      uptake was assessed. The addition of bifidobacteria significantly reduced the
      InsP(6) + InsP(5) concentrations compared to control samples. Fe-dialyzable
      contents for samples with bifidobacteria were increased 2.3-5.6-fold, and
      dialyzability was improved by 2.6-8.6% compared to controls. However, this was
      not reflected in an increase of Fe uptake by Caco-2 cells as was predicted by the
      phytate/Fe molar ratios. The results demonstrated the usefulness of phytase
      producing bifidobacteria to reduce phytate during the breadmaking process and to
      increase Fe accessibility, although the effects appeared to be still insufficient
      to improve Fe bioavailability in Caco-2 cells. Further refinement of the use of
      phytase-producing bifidobacterial strains and/or breadmaking technological
      processes is deserved for improving Fe uptake.

PMID- 22369316
TI  - Improving the performance of P3HT-fullerene solar cells with side-chain
      functionalized poly(thiophene) additives: a new paradigm for polymer design.
AB  - The motivation of this study is to determine if small amounts of designer
      additives placed at the polymer-fullerene interface in bulk heterojunction (BHJ)
      solar cells can influence their performance. A series of AB-alternating side
      chain-functionalized poly(thiophene) analogues, P1-6, are designed to selectively
      localize at the interface between regioregular poly(3-hexylthiophene) (rr-P3HT)
      and PC(n)BM (n = 61, 71). The side chains of every other repeat unit in P1-6
      contain various terminal aromatic moieties. BHJ solar cells containing ternary
      mixtures of rr-P3HT, PC(n)BM, and varying weight ratios of additives P1-6 are
      fabricated and studied. At low loadings, the presence of P1-6 consistently
      increases the short circuit current and decreases the series resistance of the
      corresponding devices, leading to an increase in power conversion efficiency
      (PCE) compared to reference P3HT/PC(61)BM cells. Higher additive loadings (>5 wt
      %) lead to detrimental nanoscale phase separation within the active layer blend
      and produce solar cells with high series resistances and low overall PCEs. Small
      perturbation transient open circuit voltage decay measurements reveal that, at
      0.25 wt % incorporation, additives P1-6 increase charge carrier lifetimes in
      P3HT/PC(61)BM solar cells. Pentafluorophenoxy-containing polymer P6 is the most
      effective side-chain-functionalized additive and yields a 28% increase in PCE
      when incorporated into a 75 nm thick rr-P3HT/PC(61)BM BHJ at a 0.25 wt % loading.
      Moreover, devices with 220 nm thick BHJs containing 0.25 wt % P6 display PCE
      values of up to 5.3% (30% PCE increase over a control device lacking P6). We
      propose that additives P1-6 selectively localize at the interface between rr-P3HT
      and PC(n)BM phases and that aromatic moieties at side-chain termini introduce a
      dipole at the polymer-fullerene interface, which decreases the rate of
      bimolecular recombination and, therefore, improves charge collection across the
      active layer.

PMID- 22369317
TI  - Transparent gold as a platform for adsorbed protein spectroelectrochemistry:
      investigation of cytochrome c and azurin.
AB  - The majority of protein spectroelectrochemical methods utilize a diffusing,
      chemical mediator to exchange electrons between the electrode and the protein. In
      such methods, electrochemical potential control is limited by mediator choice and
      its ability to interact with the protein of interest. We report an approach for
      unmediated, protein spectroelectrochemistry that overcomes this limitation by
      adsorbing protein directly to thiol self-assembled monolayer (SAM) modified, thin
      (10 nm), semitransparent gold. The viability of the method is demonstrated with
      two diverse and important redox proteins: cytochrome c and azurin. Fast,
      reversible electrochemical signals comparable to those previously reported for
      these proteins on ordinary disk gold electrodes were observed. Although the
      quantity of protein in a submonolayer adsorbed at an electrode is expected to be
      insufficient for detection of UV-vis absorption bands based on bulk extinction
      coefficients, excellent spectra were detected for each of the proteins in the
      adsorbed state. Furthermore, AFM imaging confirmed that only a single layer of
      protein was adsorbed to the electrode. We hypothesize that interaction of the
      relatively broad gold surface plasmon with the proteins' electronic transitions
      results in surface signal enhancement of the molecular transitions of between 8
      and 112 times, allowing detection of the proteins at much lower than expected
      concentrations. Since many other proteins are known to interact with gold SAMs
      and the technical requirements for implementation of these experiments are
      simple, this approach is expected to be very generally applicable to exploring
      mechanisms of redox proteins and enzymes as well as development of sensors and
      other redox protein based applications.

PMID- 22369318
TI  - Blue-emissive upconversion nanoparticles for low-power-excited bioimaging in
      vivo.
AB  - Water-soluble upconversion luminescent (UCL) nanoparticles based on triplet
      triplet annihilation (TTA) were successfully prepared by coloading sensitizer
      (octaethylporphyrin Pd complex) and annihilator (9,10-diphenylanthracene) into
      silica nanoparticles. The upconversion luminescence quantum yield of the
      nanoparticles can be as high as 4.5% in aqueous solution. As determined by
      continuous kinetic scan, the nanoparticles have excellent photostability. Such
      TTA-based upconversion nanoparticles show low cytotoxicity and were successfully
      used to label living cells with very high signal-to-noise ratio. UCL imaging with
      the nanoparticles as probe is capable of completely eliminating background
      fluorescence from either endogenous fluorophores of biological sample or the
      colabeled fluorescent probe. In particular, such blue-emissive upconversion
      nanoparticles were successfully applied in lymph node imaging in vivo of living
      mouse with excellent signal-to-noise ratio (>25), upon low-power density
      excitation of continuous-wave 532 laser (8.5 mW cm(-2)). Such high-contrast and
      low-power excited bioimaging in vivo with a blue-emissive upconversion
      nanoparticle as probe may extend the arsenal of currently available luminescent
      bioimaging in vitro and in vivo.

PMID- 22369319
TI  - 7q11.23 Microduplication: a recognizable phenotype.
AB  - Williams-Beuren syndrome is a well-known microdeletion syndrome with a
      recognizable clinical phenotype. The subtle phenotype of the reciprocal
      microduplication of the Williams-Beuren critical region has been described
      recently. We report seven further patients, and a transmitting parent, with
      7q11.23 microduplication. All our patients had speech delay, autistic features
      and facial dysmorphism consistent with the published literature. We conclude that
      the presence of specific dysmorphic features, including straight, neat eyebrows,
      thin lips and a short philtrum, in our patients with speech delay and autistic
      features provides further evidence that the children with 7q11.23
      microduplication have a recognizable phenotype.

PMID- 22369320
TI  - Thromboprophylaxis in multiple myeloma: is the evidence there?

PMID- 22369322
TI  - Decitabine for acute myeloid leukemia.
AB  - Decitabine (Dacogen((r)), Eisai Inc., NJ, USA) is a nucleoside analogue DNA
      methyltransferase inhibitor first synthesized and documented to have antileukemic
      efficacy over 40 years ago. Over the years, the dosing of decitabine has been
      refined, such that for acute myeloid leukemia, a 5-day schedule of 20 mg/m(2) is
      now commonly utilized. Owing to its relatively modest nonhematologic toxicity
      when administered in this manner, single agent decitabine has shown the greatest
      promise in antileukemic efficacy for the management of older individuals and
      others who are not candidates for more intensive therapy. Whether or not single
      agent decitabine is more safe and effective than existing therapies for older
      individuals, which markers best predict for response, and what drugs combine most
      effectively with decitabine, are all areas of active investigation at this time.

PMID- 22369323
TI  - Integrated analysis of miRNA and mRNA profiles enables target acquisition in
      human cancers.
AB  - miRNAs play a role in post-transcriptional gene regulation by translational
      repression and/or mRNA degradation in a very tissue-specific manner. In order to
      understand the function of a miRNA, it is best to identify the genes that it
      regulates. Putative mRNA targets of miRNAs identified from seed sequence matches
      are available using computational algorithms in various web-based databases.
      However, these tend to have high false-positive rates and, owing to a whole
      genome approach, cannot identify tissue/tumor specificity of regulation. The
      evaluated article presents a large amount of data analyzing global RNA expression
      in breast cancer and examines whether miRNAs are prognostic due to their effects
      on mRNA targets. This valuable and important resource of combined miRNA and mRNA
      expression in breast cancer and its subtypes has been summarized. Many studies
      have now investigated the integrated analysis of miRNA:mRNA profiles in human
      malignancies, the goal as always being to identify novel biomarkers and
      therapeutic targets for each tumor.

PMID- 22369324
TI  - How to carry out retrospective studies in metastatic renal cell cancer: two
      caveats that should be avoided.
AB  - The results achieved with targeted therapy have changed the natural course of
      kidney cancer not amenable to local therapy. Sunitinib, bevacizumab and pazopanib
      are approved in the first-line setting for patients at good/intermediate
      prognosis, while temsirolimus should be the first-line agent to be used in
      patients at poor prognosis. The oncology community has been eagerly awaiting
      results as far as second-line treatment is concerned. The RECORD-1 and AXIS
      trials provided evidence in favor of everolimus and axitinib, respectively, in
      patients pretreated with VEGF-directed agents. As the number of available agents
      grows, so does the possibility of using multiple lines of therapy with a
      potential benefit in overall survival. The third-line setting has been poorly
      investigated, and no comparative prospective trials are presently available.
      Retreatment with VEGF-directed therapy may be an option in everolimus-pretreated
      patients, with the possibility that mTOR inhibitors may reverse resistance to
      VEGF-directed therapy. Grunwald et al. presented retrospective data showing that
      retreatment with VEGF-directed targeted agents, including sunitinib,
      bevacizumab/interferon, dovitinib and sorafenib, was associated with a
      progression-free survival time of approximately 5 months. Although the evidence
      provided by retrospective studies is weak, their role in highlighting matters of
      clinical relevance deserving investigation is undoubtful, as demonstrated by the
      retrospective study discussed in this paper.

PMID- 22369325
TI  - Improving end-of-life care for head and neck cancer patients.
AB  - Despite improvements in the treatment of head and neck cancer, many patients
      still succumb to their disease. A litany of medical, psychosocial and ethical
      challenges arise in managing the end-of-life experiences within this patient
      population. In this article, we attempt to review existing data about the end-of
      life experiences of this cohort, extrapolate relevant data from other cancer
      patients, and suggest the most promising avenues for additional research and
      practice improvement for terminal head and neck cancer patients. Clinical
      decision-making for patients dying of head and neck cancer requires proactive
      consideration of quality of life, functionality, symptom control and other
      patient-centered objectives, and frequently benefits from palliative care team
      involvement. Additional research aimed toward optimizing the end of life
      experience of head and neck cancer patients and their families is greatly needed.

PMID- 22369327
TI  - Perineural invasion and spread in head and neck cancer.
AB  - Perineural involvement is a well-recognized clinicopathologic entity found in
      head and neck (H&N) cancers, including mucosal epithelial carcinomas and salivary
      gland malignancies. Perineural disease remains a diagnostic, prognostic and
      therapeutic challenge for the multidisciplinary H&N oncology team. Nerves are
      important routes of tumor spread in H&N malignancies, yet the biology and
      prognostic implications of perineural tumor growth are not fully understood. On
      balance, the available evidence suggests that it is associated with an increased
      risk of locoregional recurrence but the impact on survival remains uncertain.
      Perineural involvement has implications for locoregional disease diagnosis and
      management. MRI is the best imaging modality to detect tumor extent. Advanced
      radiotherapy technologies such as intensity-modulated radiation therapy and image
      guided radiation therapy have the potential for more accurate targeting and
      treatment of anatomically complex patterns of disease spread. This review is
      limited to nondermatologic H&N cancers.

PMID- 22369326
TI  - Differentiated thyroid cancers: a comprehensive review of novel targeted
      therapies.
AB  - Differentiated thyroid carcinoma (DTC) accounts for more than 90% of new thyroid
      cancer diagnoses, and includes papillary, follicular and Hurthle cell carcinoma.
      The prognosis for the vast majority of individuals diagnosed with DTC is
      excellent, with current treatment that includes surgery, radioactive iodine
      ablation and postoperative thyroid-stimulating hormone suppression.
      Unfortunately, the small proportion of individuals who develop radioactive iodine
      resistant recurrent disease have few treatment options, and the vast majority
      will eventually die from their disease. Recently, several novel targets for
      anticancer agents have been identified and offer new hope for thyroid cancer
      patients diagnosed with progressive disease. In addition to targeting genes
      commonly altered in thyroid cancer, which include mutations in BRAF, RAS and RET,
      proangiogenic growth factor receptors and the sodium-iodide symporter have also
      been targeted. Several clinical trials evaluating tyrosine kinase and
      angiogenesis inhibitors for treatment of individuals diagnosed with metastatic or
      treatment-refractory DTC are currently underway. The objective of this review is
      to evaluate recent clinical trials that have studied novel targeted drugs for
      treatment of DTC.

PMID- 22369328
TI  - The rise of transoral robotic surgery in the head and neck: emerging
      applications.
AB  - The use of robotics in the field of head and neck surgery has provided surgeons
      with the ability to access anatomic locations that were previously only managed
      via open techniques. This has resulted in decreased overall morbidity, excellent
      functional results and the promise of equivalent oncologic outcomes. Transoral
      robotic surgery (TORS) provides access to the oropharynx, hypopharynx, larynx,
      oral cavity, parapharyngeal space and skull base vial the oral aperture. Studies
      reviewing the application of TORS to these subsites have been promising, and for
      many applications TORS has been accepted as a safe and efficacious option for
      surgical management. However, despite these promising results, TORS remains a
      surgical instrument that requires sound surgical skill, clinical judgment and
      oncologic principles, and should be chosen based on the needs of the individual
      patient and the comfort of the treating surgeon. In this article, we review the
      history of TORS, relevant anatomy and provide a review of the literature,
      highlighting the applications, advantages, functional outcomes and disadvantages
      of TORS for each anatomic subsite.

PMID- 22369329
TI  - Mechanisms and novel approaches in overriding tyrosine kinase inhibitor
      resistance in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia is a stem cell-initiated but progenitor-driven disease
      induced by the BCR-ABL oncogene. Tyrosine kinase inhibitors (TKIs) were
      introduced in the late 1990s and have revolutionized the management of chronic
      myeloid leukemia in chronic phase. The majority of patients can now expect to
      live a normal life as long as they continue to comply with TKI treatment.
      However, in a significant proportion of cases TKI resistance develops over time,
      requiring a switch of therapy. The most frequent mechanism for drug resistance is
      the development of kinase domain mutations that reduce or completely ablate drug
      efficacy. Fortunately, the last 10 years have seen an impressive array of new
      drugs, some modeled on the mechanism of action of imatinib, others employing more
      novel approaches, for these patients.

PMID- 22369330
TI  - Predicting survival in chronic lymphocytic leukemia.
AB  - There is increasing interest in the use of prognostic markers that may predict
      survival and guide management in patients diagnosed with the early stages of
      chronic lymphocytic leukemia (CLL). Currently, the most important traditional
      prognostic factors include clinical staging, lymphocyte doubling time and beta2
      microglobulin/thymidine kinase; and the most important novel markers include
      karyotypic aberrations (typically assessed by FISH probes or CpG oligonucleotide
      karyotyping) and IgVH mutation status. Although each of these factors have
      individually shown significant correlations with survival, there is increasing
      appreciation that the most complete information may be obtained by using a
      combination of several factors in prognostic normograms or models. In this
      article, we review the current state-of-the-art with regards to CLL prognostic
      factors and discuss how they can be applied in the clinic.

PMID- 22369331
TI  - Pediatric acute myeloid leukemia.
AB  - Pediatric acute myeloid leukemia (AML) is currently associated with survival
      rates as high as 70%. However, many events still occur, side effects are
      significant, and late effects occur and can even be life-threatening. Thus, the
      treatment of pediatric AML still needs further improvement. While most study
      groups agree on several principles of AML treatment, many unanswered questions
      and even controversies remain, which will be the topic of this review. Relapsed
      AML, the most frequent event in children, will also be discussed. The
      controversies justify future clinical studies. Fortunately, biotechnical
      developments provide novel treatment targets and targeted drugs, and will enable
      minimal residual disease-driven tailored therapy. Moreover, a wide range of new
      drugs is being developed. International collaboration is required to perform
      randomized, or even single-arm clinical studies, in this setting of subgroup
      directed therapy, and fortunately is being accomplished. Therefore, optimism is
      justified and the treatment of pediatric AML will continue to improve.

PMID- 22369333
TI  - Remaining or becoming secure: parental sensitive support predicts attachment
      continuity from infancy to adolescence in a longitudinal adoption study.
AB  - In a longitudinal study with 125 early adopted adolescents, we examined
      continuity of attachment from infancy to adolescence and the role of parental
      sensitive support in explaining continuity or discontinuity of attachment.
      Assessments of maternal sensitive support and infant attachment (Strange
      Situation Procedure) were completed when infants were 12 months old. When the
      children were 14 years old, we observed mothers' sensitive support during a
      conflict discussion. The adolescents' attachment representations were assessed
      with the Adult Attachment Interview. Mothers of secure adolescents showed
      significantly more sensitive support during conflicts than did mothers of
      insecure adolescents. Overall, no continuity of attachment from infancy to
      adolescence was found. However, maternal sensitive support in early childhood and
      adolescence predicted continuity of secure attachment from 1 to 14 years, whereas
      less maternal sensitive support in early childhood but more maternal sensitive
      support in adolescence predicted children's change from insecurity in infancy to
      security in adolescence. We conclude that both early and later parental sensitive
      support are important for continuity of attachment across the first 14 years of
      life.

PMID- 22369334
TI  - Early adolescent sexual debut: the mediating role of working memory ability,
      sensation seeking, and impulsivity.
AB  - Although deficits in working memory ability have been implicated in suboptimal
      decision making and risk taking among adolescents, its influence on early sexual
      initiation has so far not been examined. Analyzing 2 waves of panel data from a
      community sample of adolescents (N = 347; Mean age[baseline] = 13.4 years),
      assessed 1 year apart, the present study tested the hypothesis that weak working
      memory ability predicts early sexual initiation and explored whether this
      relationship is mediated by sensation seeking and 2 forms of impulsivity, namely
      acting-without-thinking and temporal discounting. The 2 forms of impulsivity were
      expected to be positively associated with early sexual initiation, whereas
      sensation seeking was hypothesized to be unrelated or to have a protective
      influence, due to its positive association with working memory. Results obtained
      from structural equation modeling procedures supported these predictions and in
      addition showed that the effects of 3 prominent risk factors (Black racial
      identity, low socioeconomic background, and early pubertal maturation) on early
      sexual initiation were entirely mediated by working memory and impulsivity. The
      findings are discussed in regard to their implications for preventing early
      sexual onset among adolescents.

PMID- 22369335
TI  - Learning about causes from people: observational causal learning in 24-month-old
      infants.
AB  - How do infants and young children learn about the causal structure of the world
      around them? In 4 experiments we investigate whether young children initially
      give special weight to the outcomes of goal-directed interventions they see
      others perform and use this to distinguish correlations from genuine causal
      relations--observational causal learning. In a new 2-choice procedure, 2- to 4
      year-old children saw 2 identical objects (potential causes). Activation of 1 but
      not the other triggered a spatially remote effect. Children systematically
      intervened on the causal object and predictively looked to the effect. Results
      fell to chance when the cause and effect were temporally reversed, so that the
      events were merely associated but not causally related. The youngest children (24
      to 36-month-olds) were more likely to make causal inferences when covariations
      were the outcome of human interventions than when they were not. Observational
      causal learning may be a fundamental learning mechanism that enables infants to
      abstract the causal structure of the world.

PMID- 22369336
TI  - Co-rumination mediates contagion of internalizing symptoms within youths'
      friendships.
AB  - Peer contagion of internalizing symptoms was examined within youths' friendships
      over 6 months. Children (Grades 3 and 5) and adolescents (Grades 7 and 9) paired
      in 274 reciprocal same-sex friendship dyads completed measures of depressive and
      anxiety symptoms, co-rumination, and self-disclosure. Depression contagion was
      present for all youth, and anxiety contagion was found in the sample of girls and
      older boys. Although normative self-disclosure did not mediate the contagion
      effects, co-rumination mediated the depression contagion effect for adolescents
      and the anxiety contagion effect in the sample of girls and older boys.
      Implications for interventions with youth at risk for developing internalizing
      symptoms are discussed.

PMID- 22369337
TI  - Aggression by whom-aggression toward whom: behavioral predictors of same- and
      other-gender aggression in early childhood.
AB  - This study assessed girls' and boys' dominance-related behaviors (aggressive,
      commanding, submissive, and neutral behaviors) as they naturally occurred during
      interactions with male and female peers and evaluated the possibility that such
      behaviors elicit aggression from peers. Using a focal observational procedure,
      young girls' and boys' (N = 170; 54% boys) naturally occurring dominance-related
      behaviors and male and female peers' aggressive responses to those behaviors were
      recorded multiple times each week across the academic year. Findings suggested
      that same-gender aggression occurred at similar rates as other-gender aggression
      once tendencies toward gender-segregated play were controlled. Additionally,
      there were both gender-based similarities and differences in children's use of
      dominance-related behaviors in peer interactions and as antecedents for peers'
      aggression. The findings have implications for the literatures on aggression and
      gendered peer interactions.

PMID- 22369338
TI  - "Robovie, you'll have to go into the closet now": children's social and moral
      relationships with a humanoid robot.
AB  - Children will increasingly come of age with personified robots and potentially
      form social and even moral relationships with them. What will such relationships
      look like? To address this question, 90 children (9-, 12-, and 15-year-olds)
      initially interacted with a humanoid robot, Robovie, in 15-min sessions. Each
      session ended when an experimenter interrupted Robovie's turn at a game and,
      against Robovie's stated objections, put Robovie into a closet. Each child was
      then engaged in a 50-min structural-developmental interview. Results showed that
      during the interaction sessions, all of the children engaged in physical and
      verbal social behaviors with Robovie. The interview data showed that the majority
      of children believed that Robovie had mental states (e.g., was intelligent and
      had feelings) and was a social being (e.g., could be a friend, offer comfort, and
      be trusted with secrets). In terms of Robovie's moral standing, children believed
      that Robovie deserved fair treatment and should not be harmed psychologically but
      did not believe that Robovie was entitled to its own liberty (Robovie could be
      bought and sold) or civil rights (in terms of voting rights and deserving
      compensation for work performed). Developmentally, while more than half the 15
      year-olds conceptualized Robovie as a mental, social, and partly moral other,
      they did so to a lesser degree than the 9- and 12-year-olds. Discussion focuses
      on how (a) children's social and moral relationships with future personified
      robots may well be substantial and meaningful and (b) personified robots of the
      future may emerge as a unique ontological category.

PMID- 22369339
TI  - Competitive versus cooperative exergame play for African American adolescents'
      executive function skills: short-term effects in a long-term training
      intervention.
AB  - Exergames are videogames that require gross motor activity, thereby combining
      gaming with physical activity. This study examined the role of competitive versus
      cooperative exergame play on short-term changes in executive function skills,
      following a 10-week exergame training intervention. Fifty-four low-income
      overweight and obese African American adolescents were randomly assigned to a
      competitive exergame condition, a cooperative exergame condition, or a no-play
      control group. Youths in the competitive exergame condition improved in executive
      function skills more than did those in the cooperative exergame condition and the
      no-play control group. Weight loss during the intervention was also significantly
      positively correlated with improved executive function skills. The findings link
      competitive exergame play to beneficial cognitive outcomes for at-risk ethnic
      minority adolescents.

PMID- 22369340
TI  - Online racial discrimination and the protective function of ethnic identity and
      self-esteem for African American adolescents.
AB  - A growing body of literature has shown that being victimized online is associated
      with poor mental health. Little is known about the factors that protect youth
      from the negative outcomes that may result from these victimization experiences,
      particularly those related to race. Using a risk and resilience framework, this
      study examined the protective function of ethnic identity and self-esteem among
      African Americans who experience online racial discrimination. For the sample of
      125 adolescents, hierarchical regression results revealed that higher levels of
      ethnic identity and self-esteem significantly moderated the negative impact of
      online racial discrimination on anxiety levels. These findings show that ethnic
      identity and self-esteem can buffer the negative mental health outcomes
      associated with online racial discrimination, at least with respect to
      adolescents' anxiety. Findings from the current study have significant
      implications for adolescent adjustment given the increased time youth spend doing
      online activities.

PMID- 22369341
TI  - Friending, IMing, and hanging out face-to-face: overlap in adolescents' online
      and offline social networks.
AB  - Many new and important developmental issues are encountered during adolescence,
      which is also a time when Internet use becomes increasingly popular. Studies have
      shown that adolescents are using these online spaces to address developmental
      issues, especially needs for intimacy and connection to others. Online
      communication with its potential for interacting with unknown others, may put
      teens at increased risk. Two hundred and fifty-one high school students completed
      an in-person survey, and 126 of these completed an additional online
      questionnaire about how and why they use the Internet, their activities on social
      networking sites (e.g., Facebook, MySpace) and their reasons for participation,
      and how they perceive these online spaces to impact their friendships. To examine
      the extent of overlap between online and offline friends, participants were asked
      to list the names of their top interaction partners offline and online (Facebook
      and instant messaging). Results reveal that adolescents mainly use social
      networking sites to connect with others, in particular with people known from
      offline contexts. While adolescents report little monitoring by their parents,
      there was no evidence that teens are putting themselves at risk by interacting
      with unknown others. Instead, adolescents seem to use the Internet, especially
      social networking sites, to connect with known others. While the study found
      moderate overlap between teens' closest online and offline friends, the patterns
      suggest that adolescents use online contexts to strengthen offline relationships.

PMID- 22369342
TI  - Associations between online friendship and Internet addiction among adolescents
      and emerging adults.
AB  - The past decades have witnessed a dramatic increase in the number of youths using
      the Internet, especially for communicating with peers. Online activity can widen
      and strengthen the social networks of adolescents and emerging adults
      (Subrahmanyam & Smahel, 2011), but it also increases the risk of Internet
      addiction. Using a framework derived from Griffiths (2000a), this study examined
      associations between online friendship and Internet addiction in a representative
      sample (n = 394) of Czech youths ages 12-26 years (M = 18.58). Three different
      approaches to friendship were identified: exclusively offline, face-to-face
      oriented, Internet oriented, on the basis of the relative percentages of online
      and offline associates in participants' friendship networks. The rate of Internet
      addiction did not differ by age or gender but was associated with communication
      styles, hours spent online, and friendship approaches. The study revealed that
      effects between Internet addiction and approaches to friendship may be
      reciprocal: Being oriented toward having more online friends, preferring online
      communication, and spending more time online were related to increased risk of
      Internet addiction; on the other hand, there is an alternative causal explanation
      that Internet addiction and preference for online communication conditions young
      people's tendency to seek friendship from people met online.

PMID- 22369343
TI  - Guideline use: a survey of dietitians working with adult kidney transplant
      recipients.
AB  - AIM:   To establish current service provision as well as barriers and enablers to
      guideline implementation in the Nutritional Management of Adult Kidney Transplant
      Recipients (KTR). METHODS:   Fifteen primary renal transplant centres (15/17; 88%
      response rate) and 21 secondary renal transplant centres (21/24; 88% response
      rate) responded to an online survey addressing key questions investigating their
      current practice in the nutritional management of adult KTR. RESULTS:   Referral
      from primary to secondary sites was limited with only two sites (9%) routinely
      receiving referrals. Allocated funding for KTR at secondary sites was low (n = 4,
      14%). Many primary sites received nil or <0.5 full-time equivalent (FTE) funding
      for inpatient (n = 8, 53%); and nil or <=0.2 FTE funding for outpatient services
      (n = 9, 60%). In sites reporting FTE hours, the average dietitian-to-patient
      ratio was 1 FTE dietitian for every 383 (range 50-1280) annually transplanted
      patients. Major barriers identified in delivering nutrition services at primary
      sites included time/lack of resources and limitations with systems to identify or
      track transplant recipients. CONCLUSION:   Dietitian-to-patient ratios in the
      management of KTR at primary sites are inconsistent and likely to be inadequate
      at secondary transplant sites to implement guideline recommendations, especially
      for weight management. Investigations into the effectiveness of innovative
      interventions such as groups or telehealth are warranted, which may assist
      practitioners to achieve guideline recommendations in an environment of limited
      resources.

PMID- 22369344
TI  - High- and low-spin Fe(III) complexes of various AGE inhibitors.
AB  - Density functional theory calculations [CPCM/UM06/6-31+G(d,p)] were used to
      elucidate the structures and relative stability of Fe(III) complexes with various
      ligands that inhibit the formation of advanced glycation end products (AGEs) or
      iron overloaded disease (viz. aminoguanidine, pyridoxamine, LR-74, Amadori
      compounds, and ascorbic acid). EDTA was used as the free energy reference ligand.
      The distorted neutral octahedral complex containing one iron atom and three
      molecules of pyridoxamine [Fe(PM)(3)] was found to be the most stable. The
      stability of the complexes decreases in the following chelate sequence:
      pyridoxamine, Amadori complex, aminoguanidine, LR inhibitor, and ascorbic acid.

PMID- 22369345
TI  - Long-term cost-consequence analysis of exenatide once weekly vs sitagliptin or
      pioglitazone for the treatment of type 2 diabetes patients in the United States.
AB  - OBJECTIVE: Exenatide once-weekly (ExQW) is a GLP-1 receptor agonist shown to
      lower glucose and cardiovascular risk factors in patients with type 2 diabetes
      mellitus (T2DM). The objective of this study was to estimate the clinical
      benefits and associated economic benefits of treatment with ExQW compared with
      sitagliptin or pioglitazone in the US. METHODS: The IMS CORE Diabetes Model, a
      validated computer simulation model, was used to project lifetime clinical
      outcomes and complication costs. The costs of glucose-lowering drugs were
      excluded as not all prices were available. Baseline patient characteristics (mean
      values: age, 52.5 years; diabetes duration, 6 years; HbA1(c), 8.51%; body mass
      index, 32.12 kg/m(2)) and clinical data were derived from a phase 3 clinical
      trial that compared ExQW with sitagliptin or pioglitazone in T2DM patients. At 6
      months, patients treated with ExQW had greater improvements in HbA1(c) and body
      weight than those treated with sitagliptin or pioglitazone. Complication costs
      were extracted from published sources. Health outcomes and costs were discounted
      at 3% per year. Sensitivity analyses were performed. RESULTS: Over 35 years, and
      compared with sitagliptin or pioglitazone, ExQW increased life expectancy by,
      respectively, 0.28 (13.76 +/- 0.17 vs 13.48 +/- 0.18) and 0.17 years (13.76 +/-
      0.17 vs 13.59 +/- 0.17), and quality-adjusted life years by, respectively, 0.28
      (9.56 +/- 0.12 vs 9.28 +/- 0.12) and 0.24 years (9.56 +/- 0.12 vs 9.32 +/- 0.12).
      ExQW was associated with lower lifetime complication costs: compared with
      sitagliptin or pioglitazone, ExQW saved, respectively US$2215 (US$55,647 +/- 2039
      vs US$57,862 +/- 2159) and US$933 (US$55,647 +/- 2039 vs US$56,580 +/- 2007)
      direct cost per patient. Cost-savings resulted mainly from a lower projected
      cumulative incidence of cardiovascular diseases and neuropathic complications.
      LIMITATIONS: Short-term changes in surrogate end-points were used to project
      lifetime effects on clinical outcomes. Pharmacy costs were excluded from the
      analyses. CONCLUSIONS: Over a patient's lifetime, ExQW was projected to improve
      health and decrease diabetes-related complication costs compared with sitagliptin
      or pioglitazone.

PMID- 22369346
TI  - Direct and indirect costs associated with Dupuytren's contracture.
AB  - OBJECTIVE: To compare direct (medical and drug) and indirect (work loss) costs
      between privately insured US employees with Dupuytren's contracture (DC) and
      demographically matched controls without DC. METHODS: Employees aged 18-64 with
      >= 1 DC diagnosis (ICD-9-CM: 728.6, 718.44) with service dates 1/1/2000-3/31/2009
      were selected from a de-identified, privately insured claims database
      (n~3,000,000). The index date was defined as the most recent DC diagnosis with
      continuous eligibility for 6 months prior (baseline period) and 1 year after
      (study period) diagnosis. Employees with DC were matched 1:1 on age, region,
      gender, and index date to controls without DC, Peyronie's, or Ledderhose disease
      diagnoses in their claims histories. Descriptive analyses compared demographic
      characteristics, comorbidities, resource utilization, direct costs, and indirect
      costs inflated to 2009 dollars. RESULTS: DC employees (n=1406, mean age 49 years)
      with matched controls met the inclusion criteria. DC employees compared with
      controls had significantly (all p<0.05) higher baseline comorbidities, including
      hyperlipidemia (21.1% vs 15.6%), hypothyroidism (3.5% vs 2.0%), cancer (3.1% vs
      1.5%), and diabetes (8.1% vs 3.6%). During the study period, DC employees had
      significantly (all p<0.01) higher rates of inpatient stays (7.7% vs 5.3%),
      emergency department visits (19.8% vs 13.9%), outpatient visits (100.0% vs
      78.4%), physical therapy visits (30.2% vs 7.2%), and any prescription use (85.0%
      vs 69.2%), as well as higher mean work loss days (14.2 vs 7.3). DC employees had
      on average significantly (all p<0.01) higher annual direct costs ($5974 vs
      $3175), indirect costs ($2737 vs $1309), and total costs ($8712 vs $4485)
      compared with controls during the study period. LIMITATIONS: Findings did not
      account for lost productivity at work and were based on a privately insured,
      employed population, which may not be generalizable to all DC patients.
      CONCLUSIONS: Employees with DC had substantially higher comorbidity rates,
      utilization, and direct and indirect costs compared with demographically matched
      controls.

PMID- 22369347
TI  - Scoring the proliferative activity of haemangioma of infancy: state of the art.

PMID- 22369348
TI  - Prostate-specific antigen response to deferred combined androgen blockade therapy
      using bicalutamide predicts survival after subsequent oestrogen and docetaxel
      therapies in patients with castration-resistant prostate cancer.
AB  - What's known on the subject? and What does the study add? The additional use of
      anti-androgen (deferred combined androgen blockade [CAB] therapy) for patients
      with castration-resistant prostate cancer (CRPC) initially treated with androgen
      deprivation monotherapy (ADMT) can provide a clinical response, although the
      reported response rates vary widely. Our previous study, which reported a
      response rate of 66% to deferred CAB therapy, suggested that deferred CAB
      responders would also respond better to subsequent therapies than non-responders
      because the difference in cancer-specific survival between the deferred CAB
      responders and the non-responders was much larger than the progression-free
      survival rates for the responders. The present study showed that PSA response to
      deferred CAB therapy predicts clinical outcomes after subsequent oestrogen and
      docetaxel therapy. We propose that PSA response to deferred CAB be used for
      planning individualized treatment that includes secondary hormonal therapy and
      chemotherapy. OBJECTIVE: To evaluate whether there is any association between
      prostate-specific antigen (PSA) response to deferred combined androgen blockade
      (CAB) therapy using bicalutamide in patients with castration-resistant prostate
      cancer (CRPC), initially treated with castration monotherapy, and the clinical
      outcomes after subsequent oestrogen and docetaxel therapies. PATIENTS AND
      METHODS: Fifty-six patients with advanced prostate cancer, who were refractory to
      both initial castration monotherapy and subsequent deferred CAB, received
      oestrogen therapy (estramustine phosphate 140 or 280 mg/day in 50 patients,
      diethylstilbestrol diphosphate 100 mg/day orally in six patients). Of the 56
      patients, 33 underwent docetaxel therapy (median dose 55 mg/m(2), every 4-8
      weeks, median 6 courses) when they became refractory to oestrogen therapy. A
      deferred CAB response was defined as a decrease of >50% in PSA levels after the
      addition of bicalutamide. The difference in cancer-specific survival (CSS) after
      confirmation of resistance to initial castration monotherapy between the deferred
      CAB responders and the non-responders was evaluated, and outcomes after oestrogen
      and docetaxel therapies were also compared between the two groups. RESULTS: A
      response to deferred CAB was observed in 27 (48%) of the 56 patients. There was
      no significant difference between the responders and the non-responders in
      pretreatment clinical variables, including Gleason score, metastatic sites, PSA
      level at diagnosis, and PSA nadir during castration monotherapy. A deferred CAB
      response was a significant predictor of CSS after confirmation of resistance to
      initial castration monotherapy. The deferred CAB responders had significantly
      longer progression-free survival (PFS) (median 3.2 months in the responders, 2.1
      month in the non-responders, P = 0.04) and CSS (median 3.0 years in the
      responders, 1.5 years in the non-responders, P = 0.04) after oestrogen therapy.
      Likewise, PFS (median 8.2 months in the responders, 2.2 months in the non
      responders, P < 0.01) and CSS (median not reached in the responders, 1.4 years in
      the non-responders, P < 0.01) after docetaxel therapy was significantly longer in
      the deferred CAB responders. CONCLUSION: PSA response to deferred CAB predicts
      clinical outcomes after subsequent oestrogen and docetaxel therapies in patients
      with CRPC, and provides useful information for planning individualized optimum
      treatment courses that include secondary hormonal therapy and chemotherapy.

PMID- 22369349
TI  - Improving ChIP-seq peak-calling for functional co-regulator binding by
      integrating multiple sources of biological information.
AB  - BACKGROUND: Chromatin immunoprecipitation coupled with massively parallel
      sequencing (ChIP-seq) is increasingly being applied to study genome-wide binding
      sites of transcription factors. There is an increasing interest in understanding
      the mechanism of action of co-regulator proteins, which do not bind DNA directly,
      but exert their effects by binding to transcription factors such as the estrogen
      receptor (ER). However, due to the nature of detecting indirect protein-DNA
      interaction, ChIP-seq signals from co-regulators can be relatively weak and thus
      biologically meaningful interactions remain difficult to identify. RESULTS: In
      this study, we investigated and compared different statistical and machine
      learning approaches including unsupervised, supervised, and semi-supervised
      classification (self-training) approaches to integrate multiple types of genomic
      and transcriptomic information derived from our experiments and public database
      to overcome difficulty of identifying functional DNA binding sites of the co
      regulator SRC-1 in the context of estrogen response. Our results indicate that
      supervised learning with naive Bayes algorithm significantly enhances peak
      calling of weak ChIP-seq signals and outperforms other machine learning
      algorithms. Our integrative approach revealed many potential ERalpha/SRC-1 DNA
      binding sites that would otherwise be missed by conventional peak calling
      algorithms with default settings. CONCLUSIONS: Our results indicate that a
      supervised classification approach enables one to utilize limited amounts of
      prior knowledge together with multiple types of biological data to enhance the
      sensitivity and specificity of the identification of DNA binding sites from co
      regulator proteins.

PMID- 22369350
TI  - Ecological drift and local exposures drive enteric bacterial community
      differences within species of Galapagos iguanas.
AB  - Diet strongly influences the intestinal microbial communities through species
      sorting. Alternatively, these communicates may differ because of chance variation
      in local microbial exposures or species losses among allopatric host populations
      (i.e. ecological drift). We investigated how these forces shape enteric
      communities of Galapagos marine and land iguanas. Geographically proximate
      populations shared more similar communities within a host ecotype, suggesting a
      role for ecological drift during host colonization of the islands. Additionally,
      evidence of taxa sharing between proximate heterospecific host populations
      suggests that contemporary local exposures also influence the gut community
      assembly. While selective forces such as host-bacterial interactions or dietary
      differences are dominant drivers of intestinal community differences among hosts,
      historical and contemporary processes of ecological drift may lead to differences
      in bacterial composition within a host species. Whether such differences in
      community structure translate into geographic variation in benefits derived from
      these intimate microbial communities remains to be explored.

PMID- 22369351
TI  - Solution-phase synthesis of branched DNA hybrids based on dimer phosphoramidites
      and phenolic or nucleosidic cores.
AB  - Branched oligonucleotides with "CG zippers" as DNA arms assemble into materials
      from micromolar solutions. Their synthesis has been complicated by low yields in
      solid-phase syntheses. Here we present a solution-phase synthesis based on
      phosphoramidites of dimers and phenolic cores that produces six-arm or four-arm
      hybrids in up to 61% yield. On the level of hybrids, only the final product has
      to be purified by precipitation or chromatography. A total of five different
      hybrids were prepared via the solution-phase route, including new hybrid
      (TCG)(4)TTPA with a tetrakis(triazolylphenyl)adamantane core and trimer DNA arms.
      The new method is more readily scaled up than solid-phase syntheses, uses no more
      than 4 equiv of phosphoramidite per phenolic alcohol, and provides routine access
      to novel materials that assemble via predictable base-pairing interactions.

PMID- 22369353
TI  - Lipoarabinomannan in urine during tuberculosis treatment: association with host
      and pathogen factors and mycobacteriuria.
AB  - BACKGROUND: Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis
      (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM
      ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse
      clinical populations. We therefore explored pathogen and host factors potentially
      impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and
      culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were
      prospectively determined in adults diagnosed with TB and commencing TB treatment
      at a South African township TB clinic. Sputum TB isolates were characterised by
      IS61110-based restriction fragment length polymorphism (RFLP) and urines were
      tested for mycobacteriuria by Xpert(r) MTB/RIF assay. RESULTS: 32/199 (16.1%) of
      patients tested LAM-ELISA positive. Median optical density and proportion testing
      LAM positive remained unchanged during 2 weeks of treatment and then declined
      over 24 weeks. LAM was associated with positive sputum smear and culture status,
      HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB
      treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with
      CD4 counts of >= 200, 100-199, 50-99, and < 50 cells/MUl, was 15.2%, 32%, 42.9%,
      and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM
      positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary
      LAM was related to host immune factors, was unrelated to Mtb strain and declined
      steadily after an initial 2 weeks of TB treatment. The strong association of
      urine LAM with mycobacteriuria is a new finding, indicating frequent TB
      involvement of the renal tract in advanced HIV infection.

PMID- 22369354
TI  - Comparison of ternary bilayer mixtures with asymmetric or symmetric unsaturated
      phosphatidylcholine lipids by coarse grained molecular dynamics simulations.
AB  - We studied the phase behavior of various ternary bilayer mixtures composed of
      cholesterol, an unsaturated lipid, and a fully saturated lipid, by means of
      molecular dynamics simulations of the MARTINI coarse grain model. We aimed at
      comparing lateral organization and local properties of bilayers containing
      phosphatidylcholine (PC) lipids, either with two unsaturated tails (symmetric),
      or one unsaturated and one saturated tail (asymmetric), as the low-melting
      component of the mixture. The number of unsaturations per chain was
      systematically varied in both classes of unsaturated lipids, to account for its
      consequences in segregation. In the asymmetric unsaturated PCs, the saturated
      tail was kept identical to the hydrophobic chains of the fully saturated lipid
      component. Membranes with a symmetric or an asymmetric unsaturated lipid, with
      the same kind of unsaturated chain, show different phase behavior. Symmetric
      polyunsaturated PCs set the separation in two phases. Instead, the asymmetric
      polyunsaturated lipids induced nonideal mixing of components in single-phase
      bilayers. A significative drop of temperature, within the accessible temperature
      range, enhances the segregation in mixtures with the more unsaturated asymmetric
      PC, but still within a single phase. This different phase behavior between
      membranes with symmetric and asymmetric unsaturated PCs is also observed for
      lipids with the same total number of unsaturations. On the other hand, the degree
      of unsaturation per se enhances the segregation, by increasing the composition
      fluctuations in single-phase membranes with asymmetric PC lipids, and raising the
      line tension in the two-phase bilayer mixtures with symmetric polyunsaturated
      PCs. Dynamic clusters of unsaturated asymmetric lipids can be identified. The
      clusters show no correlation between leaflets, as observed for the phase domains
      in mixtures with the symmetric polyunsaturated PCs. Interestingly, we found that
      asymmetric PC lipids have a preferential orientation such that their saturated
      tails increase their density toward the periphery of the clusters, facing regions
      enriched in the fully saturated lipids and cholesterol. The degree of
      unsaturation increases the cluster size and also enhances the anisotropy of the
      orientation. The surface density of cholesterol follows a gradient that favors
      its interaction with the saturated tails. Such gradients in composition lead to
      gradients in order parameters, such as the conformational order and the area of
      the tails, which increases away from the unsaturated lipid clusters. We compared,
      in addition, differences in hydrophobic length mismatch between acyl chains of
      the low-melting and high-melting components, in mixtures containing either
      symmetric or asymmetric unsaturated lipids.

PMID- 22369355
TI  - Neuroendocrine tumors presenting with thyroid gland metastasis: a case series.
AB  - INTRODUCTION: Autopsy series have shown that metastasis to the thyroid gland has
      occurred in up to 24% of patients who have died of cancer. Neuroendocrine tumors
      may metastasize to thyroid gland. CASE PRESENTATIONS: Case 1 was a 17-year-old
      Turkish woman who was referred from our Endocrinology Department for a
      thyroidectomy for treatment of neuroendocrine tumor metastasis. She was treated
      with a bilateral total thyroidectomy. Histopathological examination results were
      consistent with a neuroendocrine tumor; neoplastic cells showed strong
      immunoreactivity to chromogranin A and synaptophysin, but the immunohistochemical
      profile was inconsistent with medullary thyroid carcinoma in that the tumor was
      negative for calcitonin, carcinoembryonic antigen, and thyroid transcription
      factor-1.Case 2 was a 54-year-old Turkish woman who presented with a 3-cm nodule
      on her right thyroid lobe. She had undergone surgery for a right lung mass four
      years previously. After a right pneumonectomy, thymectomy and lymph node
      dissection, a typical carcinoid tumor was diagnosed. Under ultrasonographic
      guidance, fine needle aspiration biopsy of her right thyroid pole nodule was
      performed and the biopsy was compatible with a neuroendocrine tumor metastasis.
      She was treated with a bilateral total thyroidectomy. Histopathological
      examination indicated three nodular lesions, 5 cm and 0.4 cm in diameter in her
      right lobe and 0.1 cm in diameter in her left lobe. The tumors were consistent
      with a neuroendocrine phenotype, showing strong immunoreactivity to chromogranin
      A and synaptophysin. CONCLUSION: Thyroid nodules detected during follow-up of
      neuroendocrine tumor patients should be thoroughly investigated. A fine needle
      aspiration biopsy of the thyroid confirms the diagnosis in most cases and leads
      to appropriate management of those patients and may prevent unnecessary treatment
      approaches.

PMID- 22369356
TI  - Determination of lasalocid residues in the tissues of broiler chickens by liquid
      chromatography-tandem mass spectrometry.
AB  - Lasalocid is a polyether ionophoric coccidiostat used for the prevention of
      coccidiosis in poultry at a prescribed concentration and during a certain time
      interval. Due to a public health concern about the presence of coccidiostat
      residues in poultry, the aim of the present study was to determine the levels of
      lasalocid residues in the edible tissues of broiler chickens (breast muscle,
      thigh muscle, heart, liver, gizzard, kidneys and skin/fat) fed commercially
      produced feed containing 100 mg kg-1) of lasalocid in complete feed throughout
      the 5-day withdrawal period (WP). The residues were investigated by liquid
      chromatography coupled with electrospray ionisation (ESI) tandem mass
      spectrometry (MS/MS) with triple quadrupole. The limit of detection (LOD) and the
      limit of quantification (LOQ) of the method were 0.47 and 1.44 ug kg-1,
      respectively. The average recovery based on the matrix-fortified calibrations for
      chicken tissues ranged between 79% and 98%. Lasalocid was found to accumulate in
      the liver, followed by the heart, skin/fat, kidneys, thigh muscle and gizzard.
      The lowest concentrations of lasalocid residues were found in the breast muscle.
      On day 5 of the WP, residue concentrations of lasalocid did not decline below the
      LOQ of the method, but were far below the maximum residue level (MRL) established
      for lasalocid in poultry from 20 to 100 ug kg-1 by European Commission Regulation
      (EU) No. 37/2010. The results confirmed that the WP established for lasalocid is
      sufficient to ensure the decline of its residues in the tissues of broiler
      chickens to the safe residue level.

PMID- 22369357
TI  - An interesting case of primary spinal arachnoiditis.
AB  - Spinal arachnoiditis describes inflammation of the meninges, subarachnoid space
      and, in most cases, also involve the pial layer. The vast majority of cases
      described are secondary and are preceded by a known event, for example,. trauma,
      infections or irritative substances. Here, we present the case of primary spinal
      arachnoiditis. A 35-year-old lady was referred to the neurosurgical services in
      Dublin, Ireland with a 15-month history of progressive, right lower limb
      weakness. Magnetic resonance imaging revealed cystic distortion of the lumbar
      spinal canal extending up to the conus. Initially, an L2-L4 laminectomy was
      performed revealing thickened and adherent arachnoid with a large cyst in the
      spinal canal. Four months after initial operation, the patient represented with
      bilateral lower limb weakness and loss of detrusor function. Repeat magnetic
      resonance imaging was performed, which showed the development of a syrinx in the
      patient's thoracic spine. We then performed a T9-T10 laminectomy, midline
      myelotomy and insertion of a syringe-arachnoid shunt. Post-operative imaging
      showed resolution of the syrinx and a vast improvement in lower limb power. The
      patient also regained bladder control. In conclusion, spinal arachnoiditis is a
      clearly defined pathological and radiological entity with a highly variable
      clinical presentation. It is exceedingly difficult to treat as there is no
      recognised treatment currently, with most interventions aimed at symptomatic
      relief.

PMID- 22369358
TI  - Genomic signatures and gene networking: challenges and promises.
AB  - This is an editorial report of the supplement to BMC Genomics that includes 15
      papers selected from the BIOCOMP'10 - The 2010 International Conference on
      Bioinformatics & Computational Biology as well as other sources with a focus on
      genomics studies. BIOCOMP'10 was held on July 12-15 in Las Vegas, Nevada. The
      congress covered a large variety of research areas, and genomics was one of the
      major focuses because of the fast development in this field. We set out to launch
      a supplement to BMC Genomics with manuscripts selected from this congress and
      invited submissions. With a rigorous peer review process, we selected 15
      manuscripts that showed work in cutting-edge genomics fields and proposed
      innovative methodology. We hope this supplement presents the current
      computational and statistical challenges faced in genomics studies, and shows the
      enormous promises and opportunities in the genomic future.

PMID- 22369359
TI  - Profiling ascidian promoters as the primordial type of vertebrate promoter.
AB  - BACKGROUND: CpG islands are observed in mammals and other vertebrates, generally
      escape DNA methylation, and tend to occur in the promoters of widely expressed
      genes. Another class of promoter has lower G+C and CpG contents, and is thought
      to be involved in the spatiotemporal regulation of gene expression. Non
      vertebrate deuterostomes are reported to have a single class of promoter with
      high-frequency CpG dinucleotides, suggesting that this is the original type of
      promoter. However, the limited annotation of these genes has impeded the large
      scale analysis of their promoters. RESULTS: To determine the origins of the two
      classes of vertebrate promoters, we chose Ciona intestinalis, an invertebrate
      that is evolutionarily close to the vertebrates, and identified its transcription
      start sites genome-wide using a next-generation sequencer. We indeed observed a
      high CpG content around the transcription start sites, but their levels in the
      promoters and background sequences differed much less than in mammals. The CpG
      rich stretches were also fairly restricted, so they appeared more similar to
      mammalian CpG-poor promoters. CONCLUSIONS: From these data, we infer that CpG
      islands are not sufficiently ancient to be found in invertebrates. They probably
      appeared early in vertebrate evolution via some active mechanism and have since
      been maintained as part of vertebrate promoters.

PMID- 22369360
TI  - In silico secretome analysis approach for next generation sequencing
      transcriptomic data.
AB  - BACKGROUND: Excretory/secretory proteins (ESPs) play a major role in parasitic
      infection as they are present at the host-parasite interface and regulate host
      immune system. In case of parasitic helminths, transcriptomics has been used
      extensively to understand the molecular basis of parasitism and for developing
      novel therapeutic strategies against parasitic infections. However, none of
      transcriptomic studies have extensively covered ES protein prediction for
      identifying novel therapeutic targets, especially as parasites adopt non
      classical secretion pathways. RESULTS: We developed a semi-automated
      computational approach for prediction and annotation of ES proteins using
      transcriptomic data from next generation sequencing platforms. For the prediction
      of non-classically secreted proteins, we have used an improved computational
      strategy, together with homology matching to a dataset of experimentally
      determined parasitic helminth ES proteins. We applied this protocol to analyse
      454 short reads of parasitic nematode, Strongyloides ratti. From 296231 reads, we
      derived 28901 contigs, which were translated into 20877 proteins. Based on our
      improved ES protein prediction pipeline, we identified 2572 ES proteins, of which
      407 (1.9%) proteins have classical N-terminal signal peptides, 923 (4.4%) were
      computationally identified as non-classically secreted while 1516 (7.26%) were
      identified by homology to experimentally identified parasitic helminth ES
      proteins. Out of 2572 ES proteins, 2310 (89.8%) ES proteins had homologues in the
      free-living nematode Caenorhabditis elegans and 2220 (86.3%) in parasitic
      nematodes. We could functionally annotate 1591 (61.8%) ES proteins with protein
      families and domains and establish pathway associations for 691 (26.8%) proteins.
      In addition, we have identified 19 representative ES proteins, which have no
      homologues in the host organism but homologous to lethal RNAi phenotypes in C.
      elegans, as potential therapeutic targets. CONCLUSION: We report a comprehensive
      approach using freely available computational tools for the secretome analysis of
      NGS data. This approach has been applied to S. ratti 454 transcriptomic data for
      in silico excretory/secretory proteins prediction and analysis, providing a
      foundation for developing new therapeutic solutions for parasitic infections.

PMID- 22369362
TI  - Thermal noise in aqueous quadrupole micro- and nano-traps.
AB  - Recent simulations and experiments with aqueous quadrupole micro-traps have
      confirmed a possibility for control and localization of motion of a charged
      particle in a water environment, also predicting a possibility of further
      reduction of the trap size to tens of nano-meters for trapping charged bio
      molecules and DNA segments. We study the random thermal noise due to Brownian
      motion in water which significantly influences the trapping of particles in an
      aqueous environment. We derive the exact, closed-form expressions for the thermal
      fluctuations of position and velocity of a trapped particle and thoroughly
      examine the properties of the rms for the fluctuations as functions of the system
      parameters and time. The instantaneous signal transferring mechanism between the
      velocity and position fluctuations could not be achieved in the previous phase
      average approaches.

PMID- 22369363
TI  - Stability of emulsified heavy oil: the combined effects of deterministic DLVO
      forces and random surface charges.
AB  - When dispersed in aqueous solution, droplets of bitumen (extra heavy oil) are
      known to acquire negative surface charges. The resulting electrostatic repulsion,
      according to traditional DLVO theory, is far too strong for any droplet
      coalescence to occur. However, from experience it is known that bitumen droplets
      do coalesce in aqueous suspensions. Furthermore, the process appears to be
      random, with the probability of coalescence increasing sharply with the drop
      size. To explain these facts, we modeled the bitumen-water interface as a
      heterogeneous surface comprising charged "patches"; the zeta potentials of the
      patches constitute a random variable that is assumed to be Gaussian. The
      traditional DLVO theory, according to this model, remains sound on the local
      scale (i.e., for patches interacting across an intervening water layer). Such a
      theory can predict the probabilities of coalescence in remarkable detail. A
      parameter central to this theory is the lateral extent of the charged patches,
      which was estimated to be in the neighborhood of 0.6 MUm.

PMID- 22369361
TI  - Klebsiella aerogenes UreF: identification of the UreG binding site and role in
      enhancing the fidelity of urease activation.
AB  - The Ni-containing active site of Klebsiella aerogenes urease is assembled through
      the concerted action of the UreD, UreE, UreF, and UreG accessory proteins. UreE
      functions as a metallochaperone that delivers Ni to a UreD-UreF-UreG complex
      bound to urease apoprotein, with UreG serving as a GTPase during enzyme
      activation. This study focuses on the role of UreF, previously proposed to act as
      a GTPase activating protein (GAP) of UreG. Sixteen conserved UreF surface
      residues that may play roles in protein-protein interactions were independently
      changed to Ala. When produced in the context of the entire urease gene cluster,
      cell-free extracts of nine site-directed mutants had less than 10% of the wild
      type urease activity. Enrichment of the variant forms of UreF, as the UreE-F
      fusion proteins, uniformly resulted in copurification of UreD and urease
      apoprotein, whereas UreG bound to only a subset of the species. Notably, weakened
      interaction with UreG correlated with the low-activity mutants. The affected
      residues in UreF map to a distinct surface on the crystal structure, defining the
      UreG binding site. In contrast to the hypothesis that UreF is a GAP, the UreD
      UreF-UreG-urease apoprotein complex containing K165A UreF exhibited significantly
      greater levels of GTPase activity than that containing the wild-type protein.
      Additional studies demonstrated the UreG GTPase activity was largely uncoupled
      from urease activation for the complex containing this UreF variant. Further
      experiments with these complexes provided evidence that UreF gates the GTPase
      activity of UreG to enhance the fidelity of urease metallocenter assembly,
      especially in the presence of the noncognate metal Zn.

PMID- 22369364
TI  - Distribution and function of allantoin (5-ureidohydantoin) in rice grains.
AB  - Despite increasing knowledge of allantoin as a phytochemical involved in rice,
      relatively little is known about its distribution and function in rice grains. In
      this study, allantoin was quantified in 15 Chinese rice grains, and its contents
      varied with grain fraction, cultivar, and genotype. Bran always had the highest
      allantoin level, followed by brown rice and milled rice. Hull contained the
      lowest allantoin content. Allantoin in japonica bran ranged from 70 to 171 MUg/g
      but rarely exceeded 100 MUg/g in indica bran. There was a positive relationship
      between allantoin level in grains and seedling survival in seedbeds under low
      temperature or water deficit. Exogenous allantoin stimulated plant growth,
      increased soluble sugar and free proline contents, and decreased malondialdehyde
      content in rice seedlings. However, allantoin did not show any antioxidant
      activity through free radical-scavenging capacity, reducing power, linoleic acid
      peroxidation inhibition, and chelating activity. The results suggest that
      allantoin in rice grains may play some roles in providing plant stress protection
      but not serving as a beneficial health antioxidant.

PMID- 22369365
TI  - Trapping single polar molecules in SiC nanomesh via out-of-plane dipoles.
AB  - The self-assembly of nonplanar chloroaluminum phthalocyanine (ClAlPc) molecules
      as well-ordered single-molecule dipole arrays on the silicon carbide (SiC)
      nanomesh substrate was investigated using low temperature scanning tunneling
      microscopy. ClAlPc exclusively adsorbs in the center of the SiC nanomesh holes
      with its inherent dipole (from Cl to Al) pointing toward the substrate. The
      dipole can be inverted by a positively biased tip with a threshold tip voltage of
      3.3 V. We deduce that the interaction between the intrinsic dipole of ClAlPc and
      the periodic out-of-plane component of the surface dipole on the SiC nanomesh
      plays a significant role in the dipole array formation.

PMID- 22369367
TI  - Relationships between exploratory eye movement dysfunction and clinical symptoms
      in schizophrenia.
AB  - AIM: Many psychophysiological tests have been widely researched in the search for
      a biological marker of schizophrenia. The exploratory eye movement (EEM) test
      involves the monitoring of eye movements while subjects freely view geometric
      figures. Suzuki et al. (2009) performed discriminant analysis between
      schizophrenia and non-schizophrenia subjects using EEM test data; consequently,
      clinically diagnosed schizophrenia patients were identified as having
      schizophrenia with high probability (73.3%). The aim of the present study was to
      investigate the characteristics of schizophrenia patients who were identified as
      having schizophrenia on EEM discriminant analysis (SPDSE) or schizophrenia
      patients who were identified as not having schizophrenia on EEM discriminant
      analysis (SPDNSE). METHODS: The data for the 251 schizophrenia subjects used in
      the previous discriminant-analytic study were analyzed, and the demographic or
      symptomatic characteristics of SPDSE and SPDNSE were investigated. As for the
      symptomatic features, a factor analysis of the Brief Psychiatric Rating Scale
      (BPRS) rating from the schizophrenia subjects was carried out. RESULTS: Five
      factors were found for schizophrenia symptoms: excitement/hostility; negative
      symptoms; depression/anxiety; positive symptoms; and disorganization. SPDSE had
      significantly higher factor scores for excitement/hostility, negative symptoms
      and disorganization than SPDNSE. Furthermore, the BPRS total score for the SPDSE
      was significantly higher than that for the SPDNSE. CONCLUSION: SPDSE may be a
      disease subtype of schizophrenia with severe symptoms related to
      excitement/hostility, negative symptoms and disorganization, and EEM parameters
      may detect this subtype. Therefore, the EEM test may be one of the contributors
      to the simplification of the heterogeneity of schizophrenia.

PMID- 22369366
TI  - Designed compounds for recognition of 10 base pairs of DNA with two at binding
      sites.
AB  - Short AT base pair sequences that are separated by a small number of GCs are
      common in eukaryotic parasite genomes. Cell-permeable compounds that bind
      effectively and selectively to such sequences present an attractive therapeutic
      approach. Compounds with linked, one or two amidine-benzimidazole-phenyl (ABP)
      motifs were designed, synthesized, and evaluated for binding to adjacent AT sites
      by biosensor-surface plasmon resonance (SPR). A surprising feature of the linked
      ABP motifs is that a set of six similar compounds has three different minor
      groove binding modes with the target sequences. Compounds with one ABP bind
      independently to two separated AT sites. Unexpectedly, compounds with two ABP
      motifs can bind strongly either as monomers or as cooperative dimers to the full
      site. The results are supported by mass spectrometry and circular dichroism, and
      models to explain the different binding modes are presented.

PMID- 22369368
TI  - A potential explanation of some established major risk factors for autism.
AB  - Baron-Cohen hypothesized that a cause of autism in infants is exposure to high
      concentrations of intrauterine testosterone concentrations. Some of the
      subsequent research on this hypothesis has focused on the possibility that the
      source of this testosterone is the fetus; however, this review shows that if the
      source is taken to be the mother, then many of the established risk factors for
      autism could be explained. If that were correct, it would follow that high
      maternally derived intrauterine androgen concentrations may be a major
      environmental cause of autism.

PMID- 22369369
TI  - Should genetic testing go digital?

PMID- 22369370
TI  - Phosphorylated alpha-synuclein as a potential biomarker for Parkinson's disease
      and related disorders.

PMID- 22369372
TI  - KRAS mutational test for metastatic colorectal cancer patients: not just a
      technical problem.
AB  - The identification of KRAS and BRAF mutations as predictive molecular alterations
      of resistance to EGF receptor monoclonal antibody therapy in metastatic
      colorectal cancer have significantly improved the selection of patients more
      likely to be eligible for the treatment with these targeted agents. Several
      methods are available for KRAS and BRAF mutation detection but few studies have
      compared different techniques, especially in the clinical setting. In this
      article, we contextualize the wobble-enhanced amplification refractory mutation
      sequencing method for the identification of KRAS and BRAF mutations with the
      other methodologies frequently used for the assessment of these alterations in
      colorectal cancer, discussing advantages and limitations over other frequently
      used diagnostic methods.

PMID- 22369373
TI  - BRAF mutation testing in clinical practice.
AB  - Serine/threonine-protein kinase BRAF, a downstream effector of the RAS oncogene
      along the MEK/ERK signaling pathway, has emerged as an important biological
      marker for diagnosis, prognosis and therapeutic guidance for human cancers. The
      high prevalence of BRAF(V600E)  activating mutation in papillary thyroid
      carcinoma, cutaneous malignant melanoma and hairy cell leukemia implies that the
      mutation is an important 'driver' or 'codriver' in the development of a subset of
      these cancers. Diagnostically, the BRAF(V600E)  mutation is a powerful molecular
      marker for papillary thyroid carcinoma and, quite possibly, hairy cell leukemia
      as well. Cancers with a BRAF mutation are generally more aggressive than their
      counterparts without the mutation. Importantly, mutant BRAF has been a highly
      attractive target for precision cancer therapy. Indeed, recent studies in the
      clinical trials of BRAF inhibitors in patients with malignant melanoma are
      changing the treatment paradigm of this highly lethal disease. BRAF mutation
      testing using highly sensitive and specific methodology in a molecular diagnostic
      laboratory is essential in the current clinical practice of oncology.

PMID- 22369374
TI  - Using NF-kappaB as a molecular target for theranostics in radiation oncology
      research.
AB  - Resistance of cancer cells to chemotherapy and/or radiotherapy is a major
      challenge to current anticancer treatment. The NF-kappaB signaling pathway plays
      an important role in tumor development and progression, and results in
      unsatisfactory treatment outcome. Inhibition of the NF-kappaB signaling cascade
      may sensitize the resistant cancer cells to chemotherapy and/or radiotherapy.
      Here, the correlation of NF-kappaB molecules with carcinogenesis and tumor
      progression, along with its significance in clinical practice, is reviewed. The
      potential clinical application of NF-kappaB and its associated molecules as
      diagnostic and therapeutic targets is also discussed.

PMID- 22369375
TI  - Breast cancer sentinel lymph node and axillary lymphadenectomy: new tools for new
      challenges.
AB  - Axillary lymph node status at the time of diagnosis is the most important
      prognostic indicator for women with breast cancer, and may influence management
      decisions. However, at present its role is controversial, as some groups
      recommend avoiding axillary lymph node dissection (ALND) in cases with metastasis
      of any size in the sentinel lymph nodes. Molecular analysis allows full
      examination of the sentinel lymph nodes in a short time period, discriminatation
      between macrometastasis, micrometastasis and isolated tumor cells, and helps to
      predict the performance of ALND. ALND may be the treatment of choice in some
      patients, even in cases of low-volume metastasis, as chemotherapy does not
      control regional disease well. In addition, the collection of metastatic cells,
      as well as the local immune surveillance, is susceptible to further molecular
      studies that will offer prognostic and predictive information, which may have an
      impact on therapeutic decisions, so that individualized treatments can be
      adequately designed.

PMID- 22369376
TI  - Technological advances in DNA sequence enrichment and sequencing for germline
      genetic diagnosis.
AB  - The potential applications of next-generation sequencing technologies in
      diagnostic laboratories have become increasingly evident despite the various
      technical challenges that still need to be overcome to potentiate its widespread
      adoption in a clinical setting. Whole-genome sequencing is now both technically
      feasible and 'cost effective' using next-generation sequencing techniques.
      However, this approach is still considered to be 'expensive' for a diagnostic
      test. Although the goal of the US$1000 genome is fast approaching, neither the
      analytical hurdles nor the ethical issues involved are trivial. In addition, the
      cost of data analysis and storage has been much higher than initially expected.
      As a result, it is widely perceived that targeted sequencing and whole-exome
      sequencing are more likely to be adopted as diagnostic tools in the foreseeable
      future. However, the information-generating power of whole-exome sequencing has
      also sparked considerable debate in relation to its deployment in genetic
      diagnostics, particularly with reference to the revelation of incidental
      findings. In this review, we focus on the targeted sequencing approach and its
      potential as a genetic diagnostic tool.

PMID- 22369377
TI  - IP-10 release assays in the diagnosis of tuberculosis infection: current status
      and future directions.
AB  - The current state-of-the-art tests for infection with Mycobacterium tuberculosis 
      the IFN-gamma release assays - rely on accurate measurement of the cytokine IFN
      gamma. Many other potential biomarkers are expressed in concert with IFN-gamma,
      and IP-10 in particular has shown promising results. IP-10 is produced in large
      amounts, allowing for the development of new and simplified test platforms, such
      as lateral flow. In this review, we summarize the results of 22 clinical studies
      exploring the use of IP-10 as an alternative marker to IFN-gamma. The studies
      report that diagnostic accuracy of IP-10 is on par with IFN-gamma, but also that
      IP-10 may be more robust in young children and in HIV-infected individuals with
      low CD4 cell counts. We conclude the review by presenting limitations of the
      published works and outline recent developments and future directions.

PMID- 22369378
TI  - Development of chip-compatible sample preparation for diagnosis of infectious
      diseases.
AB  - Diagnosis of infectious diseases in primary care is predominantly based on
      medical history and physical examination, as conventional laboratory
      investigations are often associated with delays that are unacceptable in medical
      practice. Point-of-care testing, and especially lab-on-a-chip (LoC) systems, are
      expected to result in a considerable reduction in associated healthcare costs and
      lead to fast, but appropriate and effective, personalized therapy. Although
      appropriate sample preparation is essential for final detection, most
      microfluidic-based approaches start from samples prepared by conventional
      laboratory procedures, therefore continuing to restrict the use of these systems
      to a laboratory setting. The lack of integrated sample preparation, especially
      for sample volumes in the milliliter range, is a major drawback of existing LoC
      systems. LoC systems that start with real samples and perform a full protocol
      from sample to result are still rare. In this article, the most recent advances
      in on-chip sample preparation are reviewed for microfluidic-based diagnosis of
      infectious diseases.

PMID- 22369381
TI  - Si/InGaN core/shell hierarchical nanowire arrays and their photoelectrochemical
      properties.
AB  - Three-dimensional hierarchical nanostructures were synthesized by the halide
      chemical vapor deposition of InGaN nanowires on Si wire arrays. Single phase
      InGaN nanowires grew vertically on the sidewalls of Si wires and acted as a high
      surface area photoanode for solar water splitting. Electrochemical measurements
      showed that the photocurrent density with hierarchical Si/InGaN nanowire arrays
      increased by 5 times compared to the photocurrent density with InGaN nanowire
      arrays grown on planar Si (1.23 V vs RHE). High-resolution transmission electron
      microscopy showed that InGaN nanowires are stable after 15 h of illumination.
      These measurements show that Si/InGaN hierarchical nanostructures are a viable
      high surface area electrode geometry for solar water splitting.

PMID- 22369383
TI  - Gene selection and classification for cancer microarray data based on machine
      learning and similarity measures.
AB  - BACKGROUND: Microarray data have a high dimension of variables and a small sample
      size. In microarray data analyses, two important issues are how to choose genes,
      which provide reliable and good prediction for disease status, and how to
      determine the final gene set that is best for classification. Associations among
      genetic markers mean one can exploit information redundancy to potentially reduce
      classification cost in terms of time and money. RESULTS: To deal with redundant
      information and improve classification, we propose a gene selection method,
      Recursive Feature Addition, which combines supervised learning and statistical
      similarity measures. To determine the final optimal gene set for prediction and
      classification, we propose an algorithm, Lagging Prediction Peephole
      Optimization. By using six benchmark microarray gene expression data sets, we
      compared Recursive Feature Addition with recently developed gene selection
      methods: Support Vector Machine Recursive Feature Elimination, Leave-One-Out
      Calculation Sequential Forward Selection and several others. CONCLUSIONS: On
      average, with the use of popular learning machines including Nearest Mean Scaled
      Classifier, Support Vector Machine, Naive Bayes Classifier and Random Forest,
      Recursive Feature Addition outperformed other methods. Our studies also showed
      that Lagging Prediction Peephole Optimization is superior to random strategy;
      Recursive Feature Addition with Lagging Prediction Peephole Optimization obtained
      better testing accuracies than the gene selection method varSelRF.

PMID- 22369384
TI  - Effective gene collection from the metatranscriptome of marine microorganisms.
AB  - BACKGROUND: Metagenomic studies, accelerated by the evolution of sequencing
      technologies and the rapid development of genomic analysis methods, can reveal
      genetic diversity and biodiversity in various samples including those of
      uncultured or unknown species. This approach, however, cannot be used to identify
      active functional genes under actual environmental conditions.
      Metatranscriptomics, which is similar in approach to metagenomics except that it
      utilizes RNA samples, is a powerful tool for the transcriptomic study of
      environmental samples. Unlike metagenomic studies, metatranscriptomic studies
      have not been popular to date due to problems with reliability, repeatability,
      redundancy and cost performance. Here, we propose a normalized metatranscriptomic
      method that is suitable for the collection of genes from samples as a platform
      for comparative transcriptomics. RESULTS: We constructed two libraries, one non
      normalized and the other normalized library, from samples of marine
      microorganisms taken during daylight hours from Hiroshima bay in Japan. We
      sequenced 0.6M reads for each sample on a Roche GS FLX, and obtained 0.2M genes
      after quality control and assembly. A comparison of the two libraries showed that
      the number of unique genes was larger in the normalized library than in the non
      normalized library. Functional analysis of genes revealed that a small number of
      gene groups, ribosomal RNA genes and chloroplast genes, were dominant in both
      libraries. Taxonomic distribution analysis of the libraries suggests that
      Stramenopiles form a major taxon that includes diatoms. The normalization
      technique thus increases unique genes, functional categories of genes, and
      taxonomic richness. CONCLUSIONS: Normalization of the marine metatranscriptome
      could be useful in increasing the number of genes collected, and in reducing
      redundancies among highly expressed genes. Gene collection through the
      normalization method was effective in providing a foundation for comparative
      transcriptomic analysis.

PMID- 22369385
TI  - Participation of xenon guest in hydrogen bond network of beta-hydroquinone
      crystal.
AB  - In the beta-hydroquinone (beta-HQ)-Xe crystal, the Xe guest is placed between two
      hexagonal rings of coupled [...O-H...O-](6) H-bonds. This clathrate is treated as
      the model for monitoring the H-bonding system with the Xe participation. Three
      kinds of isotope effects due to the H/D substitution in the [...O-H...O-](6)
      bonds are considered: (i) structural changes in the clathrate (X-ray
      diffraction), (ii) variations of (129)Xe NMR signal of the guest (CP MAS), and
      (iii) variations of selected vibrations of the host (IR). This study predicts
      subtle inclination of every other hydroxyl group of the [...O-H...O-](6) rings
      into the Xe atom and formation of six Xe...H-O pairs in every cage, the frequency
      shift of the gammaOH mode due to these contacts, -DeltagammaOH(Xe...H) > 74 cm(
      1), as well as the enthalpy formation, -DeltaH(Xe...H) > 6-8 kJ mol(-1). Our IR
      results reveal a tendency of the Xe atom to form the H-bond-like network inside
      its cage and much weaker Xe...D-O interactions in the H/D substituted crystal.
      The (129)Xe NMR results do not reflect this kind of interactions due to averaging
      of the (129)Xe shielding phenomena, probably. We also predict elongation of the
      O...O distances due to the beta-HQ-Xe crystal heating and the Xe escape.

PMID- 22369386
TI  - Immunohistochemical study of epithelial markers in longitudinal and transverse
      sections of the human nail unit.

PMID- 22369388
TI  - Ovarian tumours, their characterisation and origins and ovarian screening.
AB  - Ultrasound assessment of ovarian tumours cannot accurately predict pathology.
      Recent reviews suggest that the source of many epithelial ovarian carcinomas may
      be the distal fallopian tube. Further study of the natural history of these tubal
      lesions is required before resuming ovarian screening.

PMID- 22369389
TI  - A tale of modern day Babel: the challenges of multiple languages in inner city
      hospitals.

PMID- 22369387
TI  - Evaluation of 99mTc-labeled cyclic RGD dimers: impact of cyclic RGD peptides and
      99mTc chelates on biological properties.
AB  - The main objective of this study is to explore the impact of cyclic RGD peptides
      and (99m)Tc chelates on biological properties of (99m)Tc radiotracers. Cyclic RGD
      peptide conjugates, HYNIC-K(NIC)-RGD(2) (HYNIC = 6-hydrazinonicotinyl; RGD(2) =
      E[c(RGDfK)](2) and NIC = nicotinyl), HYNIC-K(NIC)-3G-RGD(2) (3G-RGD(2) = Gly-Gly
      Gly-E[Gly-Gly-Gly-c(RGDfK)](2)), and HYNIC-K(NIC)-3P-RGD(2) (3P-RGD(2) = PEG(4)
      E[PEG(4)-c(RGDfK)](2)), were prepared. Macrocyclic (99m)Tc complexes
      [(99m)Tc(HYNIC-K(NIC)-RGD(2))(tricine)] (1), [(99m)Tc(HYNIC-K(NIC)-3G
      RGD(2))(tricine)] (2), and [(99m)Tc(HYNIC-K(NIC)-3P-RGD(2))(tricine)] (3) were
      evaluated for their biodistribution and tumor-targeting capability in athymic
      nude mice bearing MDA-MB-435 human breast tumor xenografts. It was found that 1,
      2, and 3 could be prepared with high specific activity (~111 GBq/MUmol). All
      three (99m)Tc radiotracers have two major isomers, which show almost identical
      uptake in tumors and normal organs. Replacing the bulky and highly charged
      [(99m)Tc(HYNIC)(tricine)(TPPTS)] (TPPTS = trisodium triphenylphosphine-3,3',3"
      trisulfonate) with a smaller [(99m)Tc(HYNIC-K(NIC))(tricine)] resulted in less
      uptake in the kidneys and lungs for 3. Surprisingly, all three (99m)Tc
      radiotracers shared a similar tumor uptake (1, 5.73 +/- 0.40%ID/g; 2, 5.24 +/-
      1.09%ID/g; and 3, 4.94 +/- 1.71%ID/g) at 60 min p.i. The metabolic stability of
      (99m)Tc radiotracers depends on cyclic RGD peptides (3P-RGD(2) > 3G-RGD(2) ~
      RGD(2)) and (99m)Tc chelates ([(99m)Tc(HYNIC)(tricine)(TPPTS)] > [(99m)Tc(HYNIC
      K(NIC))(tricine)]). Immunohistochemical studies revealed a linear relationship
      between the alpha(v)beta(3) expression levels and tumor uptake or tumor/muscle
      ratios of 3, suggesting that 3 is useful for monitoring the tumor alpha(v)beta(3)
      expression. Complex 3 is a very attractive radiotracer for detection of integrin
      alpha(v)beta(3)-positive tumors.

PMID- 22369390
TI  - Dealing with uterine fibroids in reproductive medicine.
AB  - Women who wish to conceive are nowadays more likely to present with uterine
      fibroids, mainly because of the delay in childbearing in our society. The
      relationship between uterine fibroids and human reproduction is still
      controversial and counselling patients might sometimes be challenging. This paper
      is to assist those involved in the management of patients of reproductive age
      presenting with uterine fibroids. The interference of fibroids on fertility
      largely depends on their location. Submucous fibroids interfere with fertility
      and should be removed in infertile patients, regardless of the size or the
      presence of symptoms. Intramural fibroids distorting the cavity reduce the
      chances of conception, while investigations on intramural fibroids not distorting
      the cavity have so far given controversial results. No evidence supports the
      systematic removal of subserosal fibroids in asymptomatic, infertile patients.
      Myomectomy is still the 'gold standard' in fibroid treatment for fertility
      wishing patients. In experienced hands, hysteroscopic myomectomy is minimally
      invasive, safe, and effective. Abdominal and laparoscopic myomectomy might be
      challenging, but potential risks could be reduced by new strategies and
      techniques.

PMID- 22369391
TI  - An overview of treatment of overactive bladder syndrome in women.
AB  - Overactive bladder syndrome (OAB) is a common, often under-reported and under
      treated condition that significantly affects the quality of life (QoL) of the
      sufferer and is associated with enormous related costs. Treatments options for
      OAB include lifestyle modifications, behavioural therapy, pharmacotherapy,
      neuromodulation, Botulinum toxin therapy and surgical interventions. For this
      paper, the Embase, Cochrane and Medline databases were searched for studies
      relating to the treatment options for OAB with (urge urinary incontinence) UUI
      from 1975 to 2010. Studies were also obtained from references of published
      reviews. Search terms used for retrieval were: overactive bladder syndrome, urge
      urinary incontinence, anticholinergics, Botulinum toxin A, sacral neuromodulation
      and clam bladder augmentation. The aim of this paper is to provide an overview of
      the treatment options currently available for women with OAB.

PMID- 22369392
TI  - Papillary thyroid cancer arising in struma ovarii.
AB  - Malignant struma ovarii is a rare clinical entity that poses a therapeutic
      challenge, as there is no 'gold standard' of care. We aimed to develop evaluation
      and treatment guidelines by reviewing presentation and outcomes of the available
      literature. We present a 60-year-old female with papillary thyroid carcinoma
      arising in a mature teratoma, and our multidisciplinary approach to care and
      follow-up. We examined 59 cases for characteristics, including rates of
      metastasis and recurrence, and response to surgical and adjuvant treatment. We
      found higher rates of metastasis and recurrence than traditionally reported, and
      found no recurrence in patients treated with oophorectomy, thyroidectomy, and I
      131 radioablation. A multimodal approach to the treatment of malignant struma
      ovarii may improve survival and decrease risk of recurrence.

PMID- 22369393
TI  - Pregnancy outcome after exposure to the probiotic Lactobacillus in early
      pregnancy.
AB  - The present study prospectively assessed pregnancy outcome of women taking
      probiotics during the periconceptional period. A group of 104 women who had taken
      Lactobacillus in early pregnancy and 200 age- and parity-matched control pregnant
      women exposed to non-teratogenic agents were also recruited into the study and
      followed-up prospectively. Median gestational age of women exposed to
      Lactobacillus was 5.2 (range: 1.9-17.6) weeks. Exposure was at a mean dose of 510
      mg/day for a median of 4.0 days (range: 1-90 days). In the exposed group,
      pregnancy outcomes included 96 live births and eight spontaneous abortions versus
      187 live births and 21 spontaneous abortions in the non-exposed group. There was
      no statistical difference in adverse pregnancy outcomes, including the number of
      spontaneous abortions, pre-term births as well as a low birth weight between the
      two groups (p > 0.05). In the exposed group, there were two (2.1%) major
      congenital malformations in comparison with five (2.7%) in the comparison group
      (p = 0.7). In conclusion, no association was identified between ingestion of
      Lactobacillus in early pregnancy for a limited period of time and adverse
      pregnancy outcomes. However, rare pregnancy outcomes may have been missed due to
      the limited sample size included in the study.

PMID- 22369394
TI  - Sonographic measurement of the umbilical cord area and the diameters of its
      vessels during pregnancy.
AB  - The objective was to determine the cross-sectional area of the umbilical cord,
      its diameter and the diameter of its vessels to establish a reference curve for
      these parameters during pregnancy, through a prospective cross-sectional study,
      including 2,310 low-risk pregnancies between 12 and 40 weeks' gestation. Means
      and standard deviations (SDs), plus the 10th, 50th and 90th percentiles for each
      measurement were calculated using polynomial regression analysis. Mann-Whitney,
      Kruskal-Wallis and Wilcoxon tests were used for statistical analysis. These
      parameters increased significantly with gestational age. The area of the cord
      also varied significantly with parity. Their new reference curves for low risk
      pregnancies were calculated using polynomial regression, and an almost linear
      increase in values was found up to 32 weeks of pregnancy, tending to stabilise
      from then onwards. The regression equation of the umbilical cord area according
      to gestational age (GA) was: -1.417 + 0.3026*GA-0.008*GA(2) + 0.000007*GA(3) and
      the degree of adjustment (R(2)) was 0.89.

PMID- 22369395
TI  - Effects of depressive and anxiety symptoms during pregnancy on pregnant,
      obstetric and neonatal outcomes: a follow-up study.
AB  - Antenatal clinics can expect at least one in five pregnant women to experience
      mental health problems, especially depression and anxiety. The present study aims
      to estimate the effects of the antenatal depressive and anxiety symptoms on
      pregnant, obstetric and neonatal outcomes. This was a prospective cohort study of
      527 pregnancies and their neonates. Whether the women were with or without
      symptoms of depression and anxiety was determined by the Hospital Anxiety and
      Depression Scale (HADS). All the participants were followed to delivery. The
      prevalence of antenatal depressive and/or anxiety was 11.0%. The antenatal
      depressive and/or anxiety symptoms during pregnancy can increase the risk of
      prolonged pregnancy (RR =4.080, 95% CI: 1.249-13.325), especially in primiparous
      women.

PMID- 22369396
TI  - Dimethyl acetals, an indirect marker of the endogenous antioxidant plasmalogen
      level, are reduced in blood lipids of Sudanese pre-eclamptic subjects whose
      background diet is high in carbohydrate.
AB  - In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating
      lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and
      dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels
      of plasmalogens, endogenous antioxidants, which play a critical role in oxidative
      protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9
      (p < 0.001) and SigmaMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n
      9, SigmaMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides
      (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte
      ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and
      SigmaDMAs in ePE, and 16:0, 18:0 and SigmaDMAs in ePC were reduced (p < 0.001) in
      the pre-eclamptic women. This study of pregnant women with high carbohydrate and
      low fat background diet suggests pre-eclampsia is associated with oxidative
      stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase
      (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and
      stearic/oleic (C18/C18:1n-9) ratios.

PMID- 22369397
TI  - The implications of a raised maternal BMI: a DGH experience.
AB  - This retrospective analysis evaluated the association between maternal body mass
      index (BMI) and the incidence of maternal and neonatal complications in those
      women delivering at a North West London hospital between January 2002 and
      December 2007. Of the women examined, obese mothers (BMI >= 30) were shown to be
      at significantly higher risk from multiple morbidities (p < 0.05), including
      gestational diabetes; antepartum haemorrhages; pre-term delivery before 37 and 33
      weeks' gestation; induction of labour; analgesia use (beyond inhalational methods
      and local infiltration); caesarean sections; massive postpartum haemorrhages;
      higher birth weights; Apgar scores < 8 at 1 min and 5 min; cord base deficits
      less than-12 and a greater need for neonatal care (SCBU, HDU, NICU) compared with
      mothers with a BMI < 30. These findings add to the growing consensus that obesity
      increases the risks involved with pregnancy. While information is filtering
      through to the general public about the overall risks of obesity, more focused
      pre-pregnancy and inter-pregnancy counselling on the implications of a raised BMI
      specifically on pregnancy is required at both primary and secondary care sector
      levels.

PMID- 22369398
TI  - Assessment of left ventricular systolic function in fetuses without myocardial
      hypertrophy of gestational diabetes mellitus mothers using velocity vector
      imaging.
AB  - The aim of this study was to quantifiably assess left ventricular systolic
      function by velocity vector imaging (VVI) in fetuses without myocardial
      hypertrophy born to gestational diabetes mellitus (GDM) mothers. Ventricular
      images (4-chamber) from 60 normal fetuses and 32 GDM fetuses were selected.
      Myocardial global and segmental peak strain and systolic strain rates were
      obtained from VVI offline software. Ejection fraction (EF) was also measured to
      assess fetal cardiac function. EF of normal fetuses and GDM group were 65.55 +/-
      4.64% and 65.72 +/- 4.92%. No difference was found in EF between the control
      group and GDM group. Global strain and strain rate of GDM groups were -13.74 +/-
      3.19% and -1.41 +/- 0.54 s(-1), respectively and were found to be lower than the
      normal group (p < 0.05). Six different segmental peak strains and peak systolic
      strain rates had identical adjacent segments not only in the control group, but
      also in GDM fetuses. It was concluded that VVI could reflect fetal cardiac
      function sensitivity. Global strain and strain rate may be useful parameters for
      assessing the fetal myocardial systolic function in diabetic mothers.

PMID- 22369399
TI  - Elective induction of labour increases caesarean section rate in low risk
      multiparous women.
AB  - The aim of this study was to compare the risk of secondary caesarean section in
      induced versus spontaneous labour in the second delivery of low risk women who
      had a vaginal delivery in their first pregnancy. The data were retrospective
      cohort from an existing regional database, comparing term (between 37 and 42
      gestational weeks) second deliveries in cephalic position in women who had
      previously given vaginal birth. Diabetes, hypertension and multiple pregnancy
      were excluded as were those with a birth weight less than 2500 g or more than
      4500 g. The difference was not significant when induction was performed after 41
      weeks. The results showed a total number of 29693 deliveries were included, 21243
      in spontaneous labour and 8450 after induction of labour. In the spontaneous
      group 312 (1.5%) underwent secondary caesarean section, as compared to 237 (2.8%)
      in the induced group, p < 0.001, OR 1.93 (95% confidence interval 1.63-2.29). It
      was concluded that elective induction of labour in low risk women who have
      previously given vaginal birth is associated with an almost doubled rate of
      secondary caesarean section if performed before 41 weeks.

PMID- 22369400
TI  - A review of 93 cases of ruptured uterus over a period of 2 years in a tertiary
      care hospital in South India.
AB  - This was a retrospective descriptive study carried out on cases in JIPMER between
      July 2008 and June 2010 among 32,080 deliveries. The study sample included 93
      women who had a ruptured uterus. Outcome variables included maternal
      characteristics, risk factors, management and complications of ruptured uterus.
      The incidence of ruptured uterus was 0.28%. Most of these women were multiparous
      (95%), between 20 and 30 years (82%). The majority had a scarred uterus (77%) and
      83% were at term gestation. Among women with a scarred uterus, 57 women (79%) had
      an unknown uterine scar type and 46 women (64%) had < 18 months' duration from
      the last caesarean section. A total of 37 women (39.7%) presented with ruptured
      uterus and a dead fetus. Out of 71 women with previous caesarean section, 46
      women (49.4%) were allowed trial of scar and developed a ruptured uterus in
      hospital. Among women with unscarred uterus, 14 presented with rupture and seven
      of these women were induced in hospital. Out of the 93 cases, 87% were managed
      with uterine repair and 12 women underwent hysterectomy. A total of 31 babies
      were born with good Apgar scores; 48 babies were stillborn. We conclude that the
      strongest association of ruptured uterus was with previous scarred uterus,
      multiparity and < 18 months' duration from the last caesarean section. There were
      no maternal deaths. Maternal morbidity was seen in 17% of cases. Perinatal
      mortality was 60.6%. As a result of the study, we have implemented changes to
      improve patients' care.

PMID- 22369401
TI  - Late postpartum eclampsia.
AB  - Studies lack data regarding incidence, risk factors, optimal treatment and
      outcome of postpartum eclampsia (PPE), convulsions within 7 days (mostly
      convulsions occur within 24 - 48 h) after delivery of fetus placenta. However,
      convulsions can occur late, up to 4 weeks. After 48 h, it is late PPE. Late
      postpartum eclampsia without preceding pre-eclampsia is rare and poses a
      diagnostic challenge. An observational study was carried out to find the
      frequency of PPE, late PPE and clinical profile for prediction/prevention of
      mortality. PPE cases were analysed from retrospective records and prospective
      cases. Of 39,050 births, 386 were eclampsia (0.98%); PPE 101 (26.1% eclampsia,
      0.26% births); 14.85% were late PPE. Of PPE, 52 (51.48%) were diagnosed
      hypertensive disorders pre-delivery and 49 (48.51%) were de novo. Prior to
      convulsions, 56 (55.5%) had headaches, six (5.9%) visual disturbances; nine (8.9)
      dizziness; four (4.0%) epigastric pain; 18 (17.8%) had no complaints. Research
      needs to continue and quality care is essential.

PMID- 22369402
TI  - Histology and prevalence of ovarian tumours in postmenopausal women: is follow-up
      required in all cases?
AB  - The objective of this study was to determine if follow-up is required for all
      ovarian tumours incidentally diagnosed in postmenopausal women, by studying the
      prevalence and histology of ovarian tumours in postmenopausal women undergoing
      hysterectomy. The histopathology of adnexa in 100 consecutive postmenopausal
      women who underwent an abdominal hysterectomy with bilateral salpingo
      oophorectomy for various indications, was reviewed. A total of 200 adnexa were
      examined. Ovarian pathology was found in 62/200 (31%). Of these 34/62 (53%) were
      unilocular cystic tumours, 9/62 (15%) were multilocular tumours, 11/62 (18%) were
      solid tumours and 8/62 (11%) were uni or multilocular with solid elements. The
      prevalence of borderline tumours was 4% and that of malignant tumours was 5%. All
      tumours < 2 cm were found to be benign. All unilocular cysts < 5 cm were benign.
      In conclusion, a vast majority of ovarian tumours in this group of women were
      benign. It may be reasonable not to follow-up women with unilocular ovarian
      tumours < 5 cm who have a normal CA125.

PMID- 22369403
TI  - A population-based case-control study of aetiological factors associated with
      vulval lichen sclerosus.
AB  - We aimed to investigate the association between possible aetiological factors and
      the risk of developing vulval lichen sclerosus (VLS). A population-based case
      control questionnaire study was performed comparing women with a diagnosis of VLS
      (n= 92), with those attending a general gynaecology clinic with no known
      anogenital dermatosis (n= 66). After adjustment for confounders, factors
      associated with VLS included a family history of diabetes mellitus (OR= 7.0, p=
      0.012) and previous pelvic surgery (OR= 4.75, p= 0.007). The use of barrier and
      progesterone only methods of contraception (OR= 0.19, p= 0.045), hormone
      replacement therapy (OR= 0.209, p= 0.025) or hayfever (OR= 0.18, p= 0.008)
      appeared to be associated with a reduced risk of VLS. In conclusion, we were
      unable to confirm many proposed aetiological theories associated with the
      development of VLS, in particular those associated with autoimmunity.

PMID- 22369404
TI  - Role of composite endpoints as an outcome assessment tool in urogenital prolapse.
AB  - Our aim was to assess the role of composite endpoints as outcome assessment tools
      in urogenital prolapse. Women undergoing surgery for urogenital prolapse were
      recruited and followed-up over 1 year. 'Cure' following surgery was defined as:
      (1) OBJECTIVE: POP-Q ordinal = 0 (pelvic organ prolapse quantification system);
      (2) Subjective: PGI-I = 1 or 2 (patient global impression of improvement); (3)
      Composite endpoint of cure: POP-Q ordinal = zero and patient goal achievement =
      60%. Our results showed 'Composite cure' of POP was in 88.7%, while objective and
      subjective cure were 85.3% and 95.5%, respectively. Defining 'success' or
      'failures' based on PGI-I scores was most discriminatory. Quality of life (QoL)
      was similar in treatment success or failure groups, where cure was measured
      objectively or using the composite endpoint. Composite endpoints should
      accurately represent cure as they combine objective measures and patient goals.
      However, these were not demonstrated as valid methods in defining success of
      prolapse surgery.

PMID- 22369405
TI  - Comparison of the clinical and quality-of-life outcomes after the inside-out TVT
      O procedure with or without concomitant transvaginal gynaecological surgery.
AB  - The study was undertaken to compare the clinical and quality-of-life (QoL)
      outcomes of the inside-out transobturator vaginal tape (TVT-O)-only procedures
      and TVT-O procedures with concomitant transvaginal gynaecological surgery for the
      treatment of stress urinary incontinence (SUI). A review of charts from January
      2006 to March 2010 identified 305 patients with urodynamic stress incontinence
      for whom we performed the TVT-O. Of the initial 305 patients, 272 (89.2%) were re
      examined for complications 1 month, 4 months, 1 year and 2-4 years
      postoperatively (122 TVT-O only; 150 TVT-O + other transvaginal gynaecological
      surgery). They were also evaluated with the Urogenital Distress Inventory
      Questionnaire (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7) 1-4 years
      after the procedure. The median follow-up was 37.3 months. The success rate was
      89.3% in the TVT-O-only group vs 93.3% in the TVT-O with concomitant
      gynaecological surgery group (p =0.729). The QoL score was quite good for 91.8%
      of the TVT-O-only patients and for 96.7% of the TVT-O with concomitant
      gynaecologic surgery patients (p =0.405). In conclusion, gynaecological
      operations performed concomitantly with the TVT-O procedure do not affect the
      clinical and QoL outcomes of the TVT-O procedure.

PMID- 22369406
TI  - Medium-term effects of a monofilament polypropylene mesh for pelvic organ
      prolapse and sexual function symptoms.
AB  - This report is aimed at describing the effects and complications of a
      polypropylene mesh in standard gynaecological practice. This is single centre
      prospective cohort observational study performed at a University affiliated
      hospital in the UK. It involved the prospective symptom assessment of 41
      consecutive patients in 2007 who underwent anterior and/or posterior Avaulta
      PlusTM or AvaultaTM Biosynthetic Support System (BARD). The validated
      International Consultation on Incontinence Modular Questionnaire - Vaginal
      Symptoms (ICIQ-VS) was completed in the clinic preoperatively. Postal
      questionnaires were sent to the patients up to 3 years postoperatively.
      Preoperatively the mean overall Quality of life (QoL) was 19.78 (SD 9.052) and at
      follow-up was 1.67 (SD 1.0) with p< 0.008. Mean VAS preoperatively was 15.00 (SD
      7.566) and at follow-up was 0.44 (SD 0.882) with p< 0.008. A decrease in this
      score over time, indicates improved symptoms. In select patients, repair with
      mesh augmentation using AvaultaTM or Avaulta PlusTM is a safe and effective
      procedure up to 3 years with a median follow-up of 27 months (range 20-36
      months).

PMID- 22369407
TI  - High rate of allergies among women with endometriosis.
AB  - Women with endometriosis frequently suffer from autoimmune inflammatory diseases,
      allergies and asthma. This study was conducted to examine whether the prevalence
      of allergies is higher in patients with endometriosis than in the control group,
      and to show potential correlation with endometriosis stages. We evaluated the
      medical files of 501 women with laparoscopically-diagnosed endometriosis and 188
      women without endometriosis enrolled in Yale University Hospital. Main outcome
      measures used were allergy on medications, complaints of sinus or perennial
      allergic rhinitis, asthma, family history of allergic disease, and correlation
      with stages of endometriosis. Our results indicated that the overall risk of
      women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9
      6.3) (p < 0.001). Significant excesses were identified for medications, sinus
      allergic rhinitis, and asthma; also, women with endometriosis were significantly
      more likely to report a positive family history of allergies. Overall, our study
      indicated a link between endometriosis and increased risk of allergic autoimmune
      disorders that should further be explored.

PMID- 22369408
TI  - Hearing levels in menopausal women and the effect of tibolone on audiological
      functions.
AB  - The aim of this study was to examine the hearing levels of menopausal and
      premenopausal women of the same age and to evaluate the effect of tibolone on
      hearing. The study involved 83 postmenopausal women. Cases using tibolone were
      grouped into the tibolone group (T-group) and women without any hormone therapy
      were grouped into the non-tibolone group (NT-group). A total of 45 premenopausal
      women of the same age were taken as controls. Hearing levels of both ears were
      measured by audiometry. Significantly lower levels of hearing threshold at
      different levels were detected in the control group compared with the other
      groups. Postmenopausal women with and without tibolone therapy have poorer
      thresholds compared with still menstruating women of the same age. Thus,
      intrinsic oestrogen at physiological levels might slow down hearing loss in
      ageing women. Tibolone had no negative effect on hearing function.

PMID- 22369409
TI  - 'See and treat' outpatient hysteroscopy with novel fibreoptic 'Alphascope'.
AB  - This paper describes an experience with the Alphascope, a fibreoptic hysteroscopy
      system (Gynecare, Ethicon Women's Health and Urology). This prospective
      observational study was carried out at a tertiary hospital in Naples, Italy. The
      study population comprised patients undergoing outpatient hysteroscopy with the
      semi-rigid Versascope Hysteroscopy System using the Alphascope. 7-Fr gauge
      mechanical instruments and 5-Fr bipolar electrodes (Versapoint, Gynecare, Ethicon
      Inc., Somerville, NJ) were used for the operative procedures. Outpatient
      hysteroscopy was successful in 97% of cases. These were diagnostic in 41%, while
      operative hysteroscopy was performed in 59% of cases. The endoscopic view was
      subjectively defined by the operator as good/excellent in 95% of procedures. A
      total of 98% of patients expressed moderate/high degree of satisfaction and only
      2% were dissatisfied. The system is successful in the outpatient setting in 95%
      of attempts.

PMID- 22369410
TI  - Pruritic urticarial papules and plaques of pregnancy.

PMID- 22369411
TI  - A pregnancy complicated with fetal growth restriction in a patient with
      dystrophic epidermolysis bullosa.

PMID- 22369412
TI  - A case of hyperreactio luteinalis associated with fetal cystic hygroma.

PMID- 22369413
TI  - Subchorionic haematoma distinct from the placental tissue at 39 weeks' gestation.

PMID- 22369414
TI  - Congenital thrombotic thrombocytopenia presenting with placental abruption.

PMID- 22369415
TI  - 1st trimester incidental abdominopelvic mass: ganglioneuroma in pregnancy.

PMID- 22369416
TI  - Spigelian hernia following laparoscopy.

PMID- 22369417
TI  - Saline infusion sonography in the accurate diagnosis of a rudimentary horn
      pregnancy.

PMID- 22369418
TI  - Torsion in a perimenopausal non-gravid uterus with infarction and gangrene of
      uterus and adnexa: a proposed means of making the diagnosis clinically.

PMID- 22369419
TI  - Adnexal torsion: don't give up on the ovary.

PMID- 22369420
TI  - Diagnostic dilemma of adnexal mass in a postmenopausal woman.

PMID- 22369421
TI  - Perforation of colon cancer into a benign ovarian cyst.

PMID- 22369422
TI  - Delayed post-coital vaginal evisceration of intestines following interval
      debulking surgery.

PMID- 22369423
TI  - Bartholin's gland squamous cell carcinoma.

PMID- 22369426
TI  - Development and validation of an LC-MS/MS method for the simultaneous
      determination of deoxynivalenol, zearalenone, T-2-toxin and some masked
      metabolites in different cereals and cereal-derived food.
AB  - An LC-MS/MS method was developed and validated for the simultaneous determination
      of deoxynivalenol, zearalenone, T-2-toxin, HT-2-toxin and metabolites, including
      3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, deoxynivalenol-3-glucoside,
      alpha-zearalenol, beta-zearalenol, zearalenone-4-glucoside, alpha-zearalenol-4
      glucoside, beta-zearalenol-4-glucoside and zearalenone-4-sulfate in maize, wheat,
      oats, cornflakes and bread. Extraction was performed with
      acetonitrile/water/acetic acid (79/20/1, v/v/v) followed by a hexane defatting
      step. After filtration, the extract was evaporated and the residue was
      redissolved in mobile phase for injection. The mobile phase, which consisted of a
      mixture of methanol and water with 10 mM ammonium acetate, was adjusted to pH 3
      with glacial acetic acid. A sample clean-up procedure was not included because of
      the low recoveries of free and masked mycotoxins and their differences in
      polarity. The method allowed the simultaneous determination of 13 Fusarium
      mycotoxins in a one-step chromatographic run using a Waters Acquity UPLC system
      coupled to a Quattro Premier XE mass spectrometer. The method was validated for
      several parameters such as linearity, apparent recovery, limit of detection,
      limit of quantification, precision, expanded measurement uncertainty and
      specificity. The limits of detection varied from 5 to 13 ng g-1; those for the
      limit of quantification from 10 to 26 ng g-1. The results of the performance
      characteristics of the developed LC-MS/MS method were in good agreement with the
      criteria mentioned in Commission Regulation (EC) No. 401/2006. Thirty samples of
      a variety of food and feed matrices were sampled and analysed between July 2010
      and January 2011.

PMID- 22369427
TI  - Fish migrate underground: the example of Delminichthys adspersus (Cyprinidae).
AB  - Complex aquatic systems of karst harbour a rich but little-investigated
      biodiversity. In Croatia and Bosnia-Herzegovina karst, temporal springs are
      inhabited by a group of minnow-like fishes that retreat to the associated ground
      water during dry seasons and spend several months underground. The most abundant
      species in this group is Delminichthys adspersus (Heckel 1843), which also has
      the most fragmented distribution range. To determine the population composition
      and dispersal patterns, and to detect potential underground migration, a large
      genetic data set comprising 544 specimens of D. adspersus covering most of its
      distribution area was analysed. Analysis of mitochondrial cytochrome b sequences
      (~1000 bp) and eight microsatellite loci showed that D. adspersus comprises at
      least three subpopulations with gene flow occurring among them. Coalescent-based
      analysis revealed a complex migration pattern, with several unidirectional
      dispersal paths, including between temporal springs that share no surface
      connection. The results of this study suggest the existence of recurrent
      underground migration of fish in a karst environment and demonstrate the
      complexity of its hydrological network. The findings are relevant to conservation
      strategies for endemic karst organisms and karst ecosystems as a whole.

PMID- 22369428
TI  - Solution-phase synthesis of branched DNA hybrids via H-phosphonate dimers.
AB  - A method for the solution-phase synthesis of branched oligonucleotides with
      tetrahedral or pseudo-octahedral geometry is described that involves the coupling
      of 3'-H-phosphonates of protected dinucleoside phosphates and organic core
      molecules. The dimer building blocks are produced by a synthesis that requires no
      chromatographic purification and that produces the dimer H-phosphonates in up to
      44% yield in less than three days of laboratory work. A total of seven different
      branched hybrids were prepared, including a new hybrid of the sequence
      (CG)(4)TBA, where TBA stands for tetrakis(p-hydroxybiphenyl)adamantane that
      assembles into a material from micromolar aqueous solution upon addition of
      MgCl(2).

PMID- 22369429
TI  - ADAM8 in squamous cell carcinoma of the head and neck: a retrospective study.
AB  - BACKGROUND: A disintegrin and metalloproteinase (ADAMs) have been associated with
      multiple malignancies. ADAMs are involved in cell fusion, cell migration,
      membrane protein shedding and proteolysis. ADAM8 has been found to be
      overexpressed in squamous cell carcinomas of the lung. A new study showed that
      ADAM8 is significantly overexpressed in metastasis of squamous cell carcinomas of
      the head and neck (HNSCC). METHODS: We determined ADAM8 levels in the serum of 79
      HNSCC patients at the time of diagnosis, in 35 patients 3 months after treatment
      and in 10 patients 1 year after therapy and compared the results to the sera of
      31 healthy volunteers. We also constructed tissue microarrays to detect ADAM8
      immunohistochemically in 100 patients. The results were correlated with the
      survival data of the patients to determine the diagnostic and prognostic value.
      RESULTS: The data demonstrated that patients with high ADAM8 expression in the
      tumor have worse survival rates. We found that high ADAM8 serum levels correlated
      with high ADAM8 expression in tumor samples. Soluble ADAM8 levels did not show
      any prognostic or diagnostic properties. CONCLUSION: In summary ADAM8 expression
      is a prognostic factor for survival of patients with head and neck squamous cell
      carcinoma.

PMID- 22369430
TI  - Pharmacological preconditioning of ATP-sensitive potassium channel openers on
      acute urinary retention-induced bladder dysfunction in the rat.
AB  - What's known on the subject? and What does the study add? Acute urinary retention
      (AUR) and catheterization for AUR (AURC) or drainage of the urine is a well
      established cause of bladder dysfunction. Previously, we reported that the
      induction of AURC significantly reduced contractile responses to both carbachol
      and KCl compared with a control group, and that this reduction was prevented by
      nicorandil and cromakalim in a dose-dependent manner; however, although we
      reported a possible beneficial effect of nicorandil and cromakalim on bladder
      dysfunction caused by AURC, its molecular mechanism is still unknown. Our study
      establishes that nicorandil and cromakalim, but not glibenclamide, prevent AURC
      induced bladder dysfunction via up-regulation of both K(IR)6.1 and K(IR)6.2 with
      a subsequent decrease in oxidative stress and decreased induction of apoptosis in
      the bladder. OBJECTIVE: To investigate whether ATP-sensitive potassium (K(ATP))
      channel openers prevent bladder injury after acute urinary retention (AUR) and
      subsequent catheterization for AUR (AURC) in the rat. MATERIALS AND METHODS:
      Eight-week-old male Sprague-Dawley rats were divided into five groups: a sham
      operated control group, an AUR group, and three AUR groups treated with:
      nicorandil (10 mg/kg); cromakalim (300 ug/kg); or glibenclamide (5 mg/kg). AUR
      was induced by intravesical infusion of 3.0 mL of saline via cystostomy with
      simultaneous clamping of the penile urethra and, after 30 min of AUR, the bladder
      was allowed to drain for 60 min. After the experimental period, bladder function
      was assessed using organ bath techniques (carbachol and KCl), and by measuring
      tissue levels of 8-isoprostane, a marker of oxidative stress. The participation
      levels of K(ATP) channel pores were investigated using ELISA and real-time PCR
      methods, respectively. The degree of apoptosis was estimated using the TUNEL
      method in the bladder smooth muscle and epithelium. RESULTS: The AURC group
      showed significantly decreased contractile responses to carbachol and KCl, and
      significant increases in tissue 8-isoprostane levels and apoptosis index in the
      epithelium compared with the control group. Nicorandil and cromakalim, but not
      glibenclamide, significantly prevented these AURC-induced alterations. The
      expressions of K(IR)6.1 and K(IR)6.2 mRNAs were significantly up-regulated by the
      induction of AURC. Nicorandil and cromakalim, but not glibenclamide,
      significantly up-regulated expressions of K(IR)6.1 and K(IR)6.2 mRNAs in the
      bladder compared with the AUR group. CONCLUSION: Our data indicate that
      nicorandil and cromakalim, but not glibenclamide, prevent AURC-induced bladder
      dysfunction via activation of K(ATP) channels, with a subsequent decrease in
      oxidative stress and decreased induction of apoptosis.

PMID- 22369431
TI  - Adsorption-induced structural transition of an interpenetrated porous
      coordination polymer: detailed exploration of free energy profiles.
AB  - Specific types of coordination polymers show an adsorption-induced structural
      transition, or so-called "gate adsorption", in which a host framework is said to
      change its structure from a "closed" nonporous phase to an "open" porous one for
      guest molecules. To identify the pathway for such a structural transition, we
      perform grand canonical Monte Carlo simulations for the adsorption of guest
      molecules in a host interpenetrated framework and calculate the free energy
      profiles of the structural changes in a complete three-dimensional space. In
      addition to the open phase found in our previous analyses along a fixed one
      dimensional path, we reveal the existence of another open configuration. Each of
      the two open phases yields the status of global minimum to the other depending on
      the external pressure, resulting in a two-step isotherm. Moreover, the shape of
      adsorption hysteresis associated with the structural transition can change
      depending on the energy barrier between a metastable and a stable state that the
      system can overcome. Our simulations not only give a comprehensive understanding
      of stepped isotherms observed empirically but also suggest that isotherms with
      hysteretic gate adsorption is closely related to the thermal fluctuation of the
      system.

PMID- 22369432
TI  - Identification of gene-oriented exon orthology between human and mouse.
AB  - BACKGROUND: Gene orthology has been well studied in the evolutionary area and is
      thought to be an important implication to functional genome annotations. As the
      accumulation of transcriptomic data, alternative splicing is taken into account
      in the assignments of gene orthologs and the orthology is suggested to be further
      considered at transcript level. Whether gene or transcript orthology, exons are
      the basic units that represent the whole gene structure; however, there is no any
      reported study on how to build exon level orthology in a whole genome scale.
      Therefore, it is essential to establish a gene-oriented exon orthology dataset.
      RESULTS: Using a customized pipeline, we first build exon orthologous
      relationships from assigned gene orthologs pairs in two well-annotated genomes:
      human and mouse. More than 92% of non-overlapping exons have at least one
      ortholog between human and mouse and only a small portion of them own more than
      one ortholog. The exons located in the coding region are more conserved in terms
      of finding their ortholog counterparts. Within the untranslated region, the 5'
      UTR seems to have more diversity than the 3' UTR according to exon orthology
      designations. Interestingly, most exons located in the coding region are also
      conserved in length but this conservation phenomenon dramatically drops down in
      untranslated regions. In addition, we allowed multiple assignments in exon
      orthologs and a subset of exons with possible fusion/split events were defined
      here after a thorough analysis procedure. CONCLUSIONS: Identification of
      orthologs at the exon level is essential to provide a detailed way to interrogate
      gene orthology and splicing analysis. It could be used to extend the genome
      annotation as well. Besides examining the one-to-one orthologous relationship, we
      manage the one-to-multi exon pairs to represent complicated exon generation
      behavior. Our results can be further applied in many research fields studying
      intron-exon structure and alternative/constitutive exons in functional genomic
      areas.

PMID- 22369433
TI  - Weak interactions between folate and osmolytes in solution.
AB  - Previous osmotic stress studies on the role of solvent in two structurally
      unrelated dihydrofolate reductases (DHFRs) found weaker binding of dihydrofolate
      (DHF) to either enzyme in the presence of osmolytes. To explain these unusual
      results, weak interactions between DHF and osmolytes were proposed, with a
      competition between osmolyte and DHFR for DHF. High osmolyte concentrations will
      inhibit binding of the cognate pair. To evaluate this hypothesis, we devised a
      small molecule approach. Dimerization of folate, monitored by nuclear magnetic
      resonance, was weakened 2-3-fold upon addition of betaine or dimethyl sulfoxide
      (DMSO), supporting preferential interaction of either osmolyte with the monomer
      (as it possesses a larger surface area). Nuclear Overhauser effect (NOE)
      spectroscopy experiments found a positive NOE for the interaction of the C3'/C5'
      benzoyl ring protons with the C9 proton in buffer; however, a negative NOE was
      observed upon addition of betaine or DMSO. This change indicated a decreased
      tumbling rate, consistent with osmolyte interaction. Osmotic stress experiments
      also showed that betaine, DMSO, and sucrose preferentially interact with folate.
      Further, studies with the folate fragments, p-aminobenzoic acid and pterin 6
      carboxylate, revealed interactions for both model compounds with betaine and
      sucrose. In contrast, DMSO was strongly excluded from the pterin ring but
      preferentially interacted with the p-aminobenzoyl moiety. These interactions are
      likely to be important in vivo because of the crowded conditions of the cell
      where weak contacts can more readily compete with specific binding interactions.

PMID- 22369434
TI  - Development of composite inorganic building blocks for MOFs.
AB  - A general direction for diversifying metal-organic frameworks (MOFs) is
      demonstrated by the synthesis of composite inorganic clusters between indium and
      s-, d-, and f-block elements. These previously unknown heterometallic clusters,
      with various nuclearity, geometry, charge, and metal-to-metal ratios,
      significantly expand the pool of inorganic building blocks that are highly
      effective for the construction of porous MOFs with high gas uptake capacity.

PMID- 22369435
TI  - Surgical treatment of acute pulmonary embolism--a 12-year retrospective analysis.
AB  - OBJECTIVES: Surgical embolectomy for acute pulmonary embolism (PE) is considered
      to be a high risk procedure and therefore a last treatment option. We wanted to
      evaluate the procedures role in modern treatment of acute PE. DESIGN: All data on
      patients treated with surgical embolectomy for acute PE were retrieved from our
      clinical database. The mortality was extracted from the Danish mortality
      register. RESULTS: From October 1998 to July 2010, 33 patients underwent surgical
      embolectomy. All procedures were done through a median sternotomy and
      extracorporeal circulation. Twenty-six patients were diagnosed with a high risk
      PE and 7 with an intermediate risk PE and intracardial pathology. Six patients
      had been insufficiently treated with thrombolysis. Thirteen patients had
      contraindication for thrombolysis. Six patients were brought to the operating
      theatre in cardiogenic shock, 8 needed ventilator support, and 1 was in cardiac
      arrest. The postoperative 30-day mortality was 6% and during the 12-year follow
      up the cumulative survival was 80% with 4 late deaths. CONCLUSION: Surgical
      pulmonary embolectomy can be performed with low mortality although the treated
      patients belong to the most compromised part of the PE population. The results
      support surgical embolectomy as a vital part of the treatment algorithm for acute
      PE.

PMID- 22369437
TI  - 2011:Year in review: from rabbits to dragons.

PMID- 22369436
TI  - Antibiotic permeation across the OmpF channel: modulation of the affinity site in
      the presence of magnesium.
AB  - We characterize the rate-limiting interaction of the antibiotic enrofloxacin with
      OmpF, a channel from the outer cell wall of  Escherichia coli . Reconstitution of
      a single OmpF trimer into planar lipid membranes allows measurement of the ion
      current through the channel. Penetration of antibiotics causes ion current
      blockages, and their frequency allows a conclusion on the kinetics of channel
      entry and exit. In contrast to other antibiotics, enrofloxacin is able to block
      the OmpF channel for several milliseconds, reflecting high affinities comparable
      to substrate-specific channels such as the maltodextrin-specific maltoporin.
      Surprisingly, the presence of a divalent ion such as Mg(2+) leads to fast
      flickering with an increase in the rates of association and dissociation. All
      atom computer modeling provides the most probable pathway able to identify the
      relevant rate-limiting interaction during antibiotic permeation. Mg(2+) has a
      high affinity for the aspartic acid at the 113 position (D113) in the center of
      the OmpF intracellular binding site. Therefore, the presence of Mg(2+) reverses
      the charge and enrofloxacin may cross the constriction region in its favorable
      orientation with the carboxylic group first.

PMID- 22369438
TI  - Development and measurement of palliative care cultural standards using clinical
      indicators.

PMID- 22369439
TI  - "Watchful waiting" for metastatic colorectal cancer, antediluvian or an option to
      be considered again?
AB  - AIM: The role of chemotherapy in metastatic colorectal cancer (mCRC) is firmly
      established and the option of watchful waiting (WW) has become an alternative
      rarely considered. However, there may be a group of patients who are diagnosed
      with low volume and asymptomatic disease and who may be suitable for a WW plan.
      METHODS: From the South Australian Cancer Registry for mCRC we examined cancer
      characteristics and outcomes of patients who were suitable for chemotherapy but
      had their treatment delayed by more than 3 months from diagnosis of metastatic
      disease. RESULTS:   Data from 417 mCRC patients who received chemotherapy as
      first intervention have been entered in the Registry to date and 38 (9.1%) had
      chemotherapy commencement delayed by more than 3 months from diagnosis. Their
      median age was 76.7 years (range 38-85). Overall 87% of patients had metachronous
      metastatic cancer with a median time to recurrence of 2.1 years (range 0.53-7.71)
      and 65.5% had single organ metastasis. Median delay from the diagnosis of
      metastatic disease to chemotherapy was 5.03 months (range 3-28). The median
      survival has yet to be reached. The 2-year overall survival is 65%. CONCLUSION:
      We found that almost 10% of all patients with mCRC had a delay in the initiation
      of chemotherapy, with most due to a WW approach based on case note review.
      Patients with a delay in chemotherapy initiation are more likely to have a single
      organ site of metastatic disease and are older than those who do not. Despite the
      treatment delay, there is no evidence of a negative impact on survival.

PMID- 22369440
TI  - Importance of health literacy in oncology.
AB  - Health literacy refers to one's ability to obtain, process and understand health
      information and services to enable sound health decision-making. This is an area
      of increasing importance due to the complexity of the health system, especially
      in the cancer setting. A certain level of health literacy is required for
      patients to fully understand health information and services to make sound
      decisions about their health care, including decisions about screening and
      treatment. Previous research has suggested that a significant proportion of the
      population may have limited health literacy. Suboptimal health literacy is an
      independent risk factor for poor health outcomes, including increased risk of
      hospitalization. Cancer patients with poor health literacy may have
      misconceptions about their disease and ineffective communication with their
      health professionals, leading to unnecessary interventions, under-treatment or
      poor adherence to their treatment plans. In addition, cancer patients who have a
      poor understanding of their disease may experience greater anxiety and be more
      dissatisfied with their care. Various strategies have been suggested to assist
      cancer patients with low health literacy. However, more work needs to be done to
      support all cancer patients with varying levels of health literacy, thus
      enhancing health experiences and health outcomes.

PMID- 22369441
TI  - The role of magnetic resonance imaging in early breast cancer.
AB  - Despite recent evidence that fails to detect a benefit in surgical and local
      recurrence outcomes in those who receive optimal surgery and adjuvant systemic
      and radiotherapy, magnetic resonance imaging (MRI) is still being employed. We
      review the recent literature to clarify the role in the use of MRI in early
      breast cancer. A literature search using the Medline and Ovid databases was
      conducted between 2004 and 2011 using the terms "magnetic resonance imaging' and
      'early breast cancer'. Only articles with clinical trials published in English in
      adult humans with available abstracts were included. Articles on high-risk women,
      response to neoadjuvant therapy, advanced breast cancer, the occult primary, the
      contralateral breast and technical articles were excluded. Articles examining the
      role of MRI in the staging of early breast cancer were retained. Over 260
      articles regarding breast MRI have been published in the last 5 years. Additional
      foci may be found in 16% of patients but the impact on the extent of surgery and
      local recurrence rate is yet to be defined. Certain sub-groups who may benefit
      include those with invasive lobular carcinoma and mammographically dense breasts
      and those for consideration of partial breast irradiation. With standard adjuvant
      radiotherapy, there is no benefit in routine MRI with respect surgical extent and
      local recurrence. Should MRI be used, pre-operative biopsy to confirm additional
      disease must be undertaken prior to a change in surgical extent of resection.
      However, MRI may be useful in the evaluation of those who can be considered for
      partial breast irradiation. Centres undertaking breast MRI must have MRI-biopsy
      capabilities and constantly audit the reporting of MRI with correlation to the
      final pathology.

PMID- 22369442
TI  - Emerging and second line therapies for the management of metastatic castration
      resistant prostate cancer: the Australian perspective.
AB  - Since the establishment of docetaxel as first-line chemotherapy for metastatic
      castration-resistant prostate cancer significant advancements have been made in
      the management of this disease. Clinical trials have investigated agents for use
      prior to docetaxel, in combination with docetaxel and agents for second-line
      treatment for patients who have progressed despite docetaxel. In addition,
      several new agents have been developed and clinically investigated in the fields
      of hormonal, cytotoxic, targeted and immune therapy, providing options either
      side of first-line chemotherapy. As a result of this considerable research
      activity, three new therapies; cabazitaxel, sipuleucel-T and abiraterone acetate,
      have each demonstrated improvement in overall survival in phase III trials and
      have been approved by the US Food and Drug Administration. With so many new
      therapies now available and in the pipeline, the management of metastatic
      castration-resistant prostate cancer is undergoing a significant and positive
      change. This article discusses current and future options for second-line therapy
      in metastatic castration-resistant prostate cancer, providing insight into the
      potential roles of these new treatment options in the Australian clinical
      setting.

PMID- 22369443
TI  - Dose optimization of tyrosine kinase inhibitors to improve outcomes in GIST.
AB  - Tyrosine kinase inhibitors such as imatinib and sunitinib have greatly improved
      clinical outcomes for patients with gastrointestinal stromal tumors (GIST). Dose
      optimization of these agents is critical and involves multiple considerations,
      including ensuring a durable response, monitoring drug blood levels to confirm
      adequate dosing, deciding whether to use high-dose imatinib or switch to second
      line sunitinib in the event of disease progression and appropriately managing
      treatment-associated side effects. Imatinib is the standard first-line therapy
      for unresectable or metastatic GIST and is also an option for the adjuvant
      treatment of resected disease. Despite the efficacy and safety of imatinib in
      patients with advanced GIST, some individuals develop primary or secondary
      resistance or intolerance to the drug. For patients with advanced disease,
      imatinib dose escalation to 800 mg/day is warranted in cases of disease
      progression on imatinib 400 mg/day. In addition, patients with documented KIT
      exon 9 mutations are likely to derive benefit from initial treatment with high
      dose imatinib to improve clinical outcomes. For patients who fail imatinib,
      sunitinib is an effective treatment option. However, the decision to use either
      high-dose imatinib or sunitinib should be based on the underlying cause of
      failure on imatinib, KIT mutational status and on whether the patient is
      intolerant of or has developed a resistance to imatinib. In this article we
      review the existing literature supporting the use of imatinib and sunitinib in
      GIST to provide a current clinical perspective on how best to use these agents in
      the management of GIST to optimize patient outcomes.

PMID- 22369444
TI  - Cost-utility and budget impact analyses of gefitinib in second-line treatment for
      advanced non-small cell lung cancer from Thai payer perspective.
AB  - AIM: To evaluate the cost utility and budget impact of second-line gefitinib for
      non-small cell lung cancer from a Thai payer perspective. METHODS:   A Markov
      model with three health states (pre-progression, post-progression and death) was
      constructed to estimate direct medical costs and outcomes comparing four
      treatment options, i.e., gefitinib, erlotinib, pemetrexed and docetaxel. The
      model followed patients for 2 years with discount rate of 3% annually. Clinical
      inputs and patients' characteristics were based on a randomized phase III trial
      (INTEREST). Costs were based on reference prices published by the Ministry of
      Public Health, Thailand, and other information related to treatment from expert
      opinion and presented in 2010. Deterministic and probabilistic sensitivity
      analyses were performed to determine the impact of model parameters on results.
      RESULTS: In the base case model, gefitinib and erlotinib yielded equal quality
      adjusted life years (QALY) but 0.0140 and 0.0110 more QALY compared with
      docetaxel and pemetrexed, respectively. Total costs were 188 848 Baht (US$6237)
      for gefitinib, 196 313 Baht (US$6483) for docetaxel, 249 177 Baht (US$8229) for
      erlotinib and 275 303 Baht (US$9092) for pemetrexed. Drug acquisition contributed
      the greatest component. A series of sensitivity analyses demonstrated the
      robustness to various parameter variations except for docetaxel cost and duration
      of treatment. The budget impact analyses demonstrate the greater the percentage
      of substitution of gefitinib for docetaxel (ranging from 10-60%) the greater the
      cost saving. CONCLUSION:   Gefitinib is a dominant cost saving strategy compared
      with docetaxel for the second-line treatment of advanced NSCLC from the Thai
      payer perspective.

PMID- 22369445
TI  - Preoperative taxane-based chemotherapy in a standardized protocol for locally
      advanced breast cancer.
AB  - AIMS: To assess the feasibility of a standardized multidisciplinary protocol for
      the management of locally advanced breast cancer (LABC). We also evaluated the
      accuracy of magnetic resonance imaging (MRI) and positron emission tomography
      (PET) in predicting the extent of residual disease. METHODS: Patients with LABC
      were offered preoperative chemotherapy of docetaxel 75 mg/m(2) , doxorubicin 50
      mg/m(2) , cyclophosphamide 500 mg/m(2) (TAC), every 21 days for six cycles, until
      progression or intolerable toxicity. MRI and PET were performed at baseline and
      six cycles. Patients underwent a mastectomy or complete local excision, followed
      by radiotherapy. Trastuzumab and endocrine treatment were recommended where
      appropriate. RESULTS: Between April 2005 and October 2006, 51 patients were
      included from three institutions, and 50 received TAC (90% commenced within 35
      days of diagnosis), with 44 patients completing six cycles (88%). Pathological
      complete response was seen in 10 patients (19.6%); all had invasive ductal
      carcinoma. No patient with invasive lobular carcinoma achieved pathological
      complete response. MRI was the most accurate method of assessing the extent of
      residual cancer. In total, 45 (88%) patients underwent surgery within the
      protocol-specified time and 12 (23%) patients had breast conservation surgery. At
      a median follow-up of 41.3 months, there were three local recurrences. Ten
      patients (19.6%) developed distant metastases, resulting in an 80% actuarial
      disease-free survival. CONCLUSION: This regimen of TAC is effective and well
      tolerated and is likely to result in improved outcomes since patients can receive
      optimal multimodality treatments.

PMID- 22369446
TI  - Evaluation of the safety and feasibility of rapid rituximab infusion.
AB  - AIM: To assess safety of rapid infusion by measuring infusion-related side
      effects and toxicities. METHODS: Participants received the first rituximab
      infusion according to the manufacturers' recommendations. If well-tolerated, they
      then received the second and subsequent infusions at a rate of 20% of the dose
      over the first 30 min and the remaining 80% over the next hour. Premedication was
      administered for all the infusions. RESULTS: A total of 243 infusions in 65
      consecutive participants were evaluated. Six experienced a grade 1 reaction and
      one a grade 3 transfusion-related adverse event. Three of these participants were
      withdrawn from the rapid infusion study. The other four participants (grade 1
      only participants) were re-challenged. The same premedication was used as in the
      first rapid infusion. On experiencing a grade 1 reaction, promethazine 12.5 mg
      i.v. was administered and infusion recommenced at 50% of the previous rate upon
      the resolution of symptoms. Three patients developed a grade 1 adverse event and
      one patient experienced no adverse reaction. The three patients who did not
      tolerate the second rapid infusion were withdrawn from this study. CONCLUSION: A
      rituximab infusion over 90-min was safe and feasible for participants who seek
      treatment at ambulatory cancer centre. The new regimen has been adopted as a
      standard practice with better resource utilization.

PMID- 22369447
TI  - Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with
      metastatic breast cancer.
AB  - AIM: The combination of a taxane and capecitabine offers synergistic antitumor
      activity. This study aimed to determine the efficacy and tolerability of a
      paclitaxel and capecitabine combination in Thai patients with metastatic breast
      cancer (MBC) not previously treated for metastatic disease. METHODS: This open
      label, single-center, non-comparative phase II study was conducted between
      December 2006 and March 2009. In all 40 MBC patients were treated with oral
      capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80
      mg/m(2) in a 3-week cycle for a total of six cycles. RESULTS: After a median
      follow up of 13.4 months, an overall objective response rate of 80%, with a
      partial response of 74% and a complete response of 5% were achieved. While 8% of
      patients achieved stable disease, 13% had progressive disease. Median time to
      progress was 8 months and median overall survival was 24.4 months. One patient
      discontinued because of hypersensitivity to paclitaxel. There was no grade 4
      toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade
      2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3),
      neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both
      of which 5% experienced grade 1 severity). CONCLUSION: A first-line regimen of
      weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC
      patients.

PMID- 22369448
TI  - Epidemiological survey of biomarkers of hepatitis virus in patients with
      extrahepatic cholangiocarcinomas.
AB  - AIM: Hepatitis virus B and C (HBV and HCV) are suggested to be risk factors for
      intrahepatic cholangiocarcinoma (ICC), but whether they are risk factors for
      extrahepatic cholangiocarcinoma (ECC) is disputed. To test the biomarkers in
      patients with ECC and further elucidate the relationship of HBV or HCV infection
      with ECC risk, we conducted a retrospective survey on hepatitis virus markers in
      patients with ECC. METHODS: A hospital-based case-control study was conducted to
      review prior infection with hepatitis virus and the seroprevalence of hepatitis
      virus markers in the patients with ECC or with benign biliary disease (BBD). HBV
      X antigen (HBxAg) was detected in the tissues by immunohistochemical staining.
      RESULTS: A total of 305 patients with ECC and 480 with BBD were enrolled in this
      study. Compared with BBD patients, ECC patients had a higher prevalence of prior
      infection with HBV (6.2 vs 2.3%) and chronic HBV infection (9 vs 1.9%). The
      overall seropositive rate for HBV markers in the two groups was 22.6 versus 6% (P
      < 0.01) and for HBxAg detection it was 75 versus 26% (P < 0.001). The
      seroprevalence of anti-HCV was 4.3% in the EEC patients and 5.6% in BBD patients
      with no significant difference between them. CONCLUSION: The high prevalence of
      HBV biomarkers in ECC strongly supports the notion that HBV infection may be a
      risk factor for ECC. The high frequency of HBxAg expression suggests its
      important role in the pathogenesis of bile duct neoplasm.

PMID- 22369449
TI  - Quantification of trends in radiation oncology infrastructure in Pakistan, 2004
      2009.
AB  - AIM: To provide objective estimates of radiation oncology infrastructure in
      Pakistan for the years 2004 and 2009 in order to quantify trends in radiotherapy
      facilities, patient load and to identify the future needs. METHODS: Nationwide
      surveys using structured questionnaires were conducted in 2005 and 2010 by the
      Institute of Radiotherapy and Nuclear Medicine, Peshawar, to assess the status of
      radiation oncology infrastructure in 2004 and 2009. The data were analyzed to
      observe the trends. RESULTS: Megavoltage teletherapy machines increased from 37
      in 2004 to 41 in 2009. New patients registered in all radiotherapy centers were
      33 369 in 2004 and 46 114 in 2009. Conventional simulators used for tumour
      localization increased from 15 to 21 and computerized tomography simulators from
      0 to 07. Radiation treatment planning systems for dose calculations of tumors and
      vital organs increased from 15 to 26 and brachytherapy units from 12 to 13. There
      were 725 patients per medical physicist in 2004 versus 632 in 2009. Patients per
      radiation oncologist were 439 in 2004 versus 549 in 2009. Number of radiotherapy
      technologists/shift/machine was 1.69 in 2004 versus 1.90 in 2009. Repair
      maintenance personnel improved from 2.11/2 megavoltage units in 2004 to 2.49 in
      2009. CONCLUSION: While there was an increase in number of radiotherapy centers,
      equipment and human resources available, this was insufficient to comply with
      international guidelines. An adequate enhancement in radiation oncology
      infrastructure is needed to cope with the predicted rise in cancer incidence.

PMID- 22369450
TI  - Pilot study evaluating the role of cardiac magnetic resonance imaging in
      monitoring adjuvant trastuzumab therapy for breast cancer.
AB  - AIM: To explore the incidence of subclinical cardiotoxicity in women treated with
      adjuvant trastuzumab in the early breast cancer setting using cardiac magnetic
      resonance imaging (cMRI). METHODS: The cardiac function and myocardial tissue
      characteristics of 25 women who had completed adjuvant trastuzumab therapy
      greater than 6 months previously was evaluated using MRI and comparing this with
      symptoms and routine echocardiography. RESULTS: Evidence of myocardial tissue
      damage was seen in two women in the absence of functional change or previous
      cardiac symptoms. CONCLUSION: Tissue characterization using cMRI may provide a
      useful tool in defining trastuzumab induced cardiotoxicity.

PMID- 22369451
TI  - Pathological responses to gemcitabine/platinum-based neoadjuvant chemotherapy for
      muscle-invasive urothelial cancer.

PMID- 22369454
TI  - Thermoelectric effect in an Aharonov-Bohm ring with an embedded quantum dot.
AB  - Thermoelectric effect is studied in an Aharonov-Bohm interferometer with an
      embedded quantum dot (QD) in the Coulomb blockade regime. The electrical
      conductance, electron thermal conductance, thermopower, and thermoelectric figure
      of-merit are calculated by using the Keldysh Green's function method. It is found
      that the figure-of-merit ZT of the QD ring may be quite high due to the Fano
      effect originated from the quantum interference effect. Moreover, the
      thermoelectric efficiency is sensitive to the magnitude of the dot-lead and inter
      lead coupling strengthes. The effect of intradot Coulomb repulsion on ZT is
      significant in the weak-coupling regime, and then large ZT values can be obtained
      at rather high temperature.

PMID- 22369455
TI  - Impact of obsessive-compulsive symptoms in Tourette's syndrome on
      neuropsychological performance.
AB  - AIM: Although inconsistencies in neuropsychological impairments in Tourette's
      syndrome (TS) have been discussed with respect to comorbid disorders, such as
      obsessive-compulsive disorder, few studies have focused on the specific
      dimensions of obsessive-compulsive symptoms (OCS) related to TS, such as
      aggression and symmetry. The aim of this study was to explore the impact of
      specific TS-related OCS on neuropsychological performance. METHODS: A series of
      neuropsychological tasks examining attention and executive functioning were
      performed in groups of 33 TS participants and 18 healthy controls. The
      neuropsychological performance of TS with Aggression OCS (n = 11) were compared
      to TS without Aggression OCS (n = 22) and controls by using MANCOVA controlling
      for age. In the same way as Aggression, we compared the performance of three
      groups by Symmetry: TS with Symmetry OCS (n = 14), TS without Symmetry OCS (n =
      19) and controls. RESULTS: TS participants with Aggression OCS tended to make
      more perseverative errors than those without. Global OCS severity and tic
      severity did not correlate with any neuropsychological performances. No
      significant differences were detected between TS participants with and without
      Symmetry OCS. CONCLUSION: Neuropsychological deficits in TS might be affected not
      by global OCS severity but by specific TS-related OCS.

PMID- 22369456
TI  - A retrospective study of AIDS-associated cryptomeningitis.
AB  - Cryptococcal meningitis has emerged as a leading cause of infectious morbidity
      and mortality in patients with AIDS. A retrospective analysis of records of HIV
      infected individuals registered in the Immunodeficiency Clinic of a tertiary care
      hospital and research institute was carried out. Records of 6900 HIV-infected
      individuals who were enrolled in the clinic between January 2002 and March 2011
      were analyzed. Records of 6900 HIV-infected individuals were screened. Ninety-one
      were diagnosed with cryptococcal meningitis (1.32%). In 68 individuals
      cryptococcal meningitis was the presenting illness. Nine patients developed
      meningitis within 6 months of starting antiretroviral treatment (ART). Six
      patients were receiving ART for more than 6 months at the time of diagnosis. The
      remaining eight patients were not on ART at the time of development of
      meningitis. The mean baseline CD4 count of patients was 77.7 +/- 61 (range, 4
      259, n=91) cells/mm(3). Seventy-four patients had a CD4 value of less than 100 at
      the time of diagnosis of cryptococcal meningitis. Eleven of these ninety-one
      patients had a relapse of cryptococcal meningitis while receiving a maintenance
      dose of fluconazole. During follow-up 37 died, two were lost to follow-up, while
      52 patients were on regular ART. Mortality due to cryptococcal meningitis
      amounted to 0.54% (37/6900). There was no correlation between survival and
      duration of ART at the time of cryptomeningitis (Pearsons chi(2)=0.241, p=0.884).
      There was a significant difference in the CD4 counts of the HIV-infected
      individuals who died with cryptomeningitis and those who survived (Pearson's
      chi(2)=9.1, df=4, p=0.05). The frequency of cryptococcal meningitis was 1.32%.
      Cryptococcal meningitis leads to high mortality in HIV patients. Management of
      cryptococcal infection remains a key facet of AIDS care in India.

PMID- 22369457
TI  - Perfect Hamming code with a hash table for faster genome mapping.
AB  - BACKGROUND: With the advent of next-generation sequencers, the growing demands to
      map short DNA sequences to a genome have promoted the development of fast
      algorithms and tools. The tools commonly used today are based on either a hash
      table or the suffix array/Burrow-Wheeler transform. These algorithms are the best
      suited to finding the genome position of exactly matching short reads. However,
      they have limited capacity to handle the mismatches. To find n-mismatches, they
      requires O(2n) times the computation time of exact matches. Therefore,
      acceleration techniques are required. RESULTS: We propose a hash-based method for
      genome mapping that reduces the number of hash references for finding mismatches
      without increasing the size of the hash table. The method regards DNA
      subsequences as words on Galois extension field GF(22) and each word is encoded
      to a code word of a perfect Hamming code. The perfect Hamming code defines
      equivalence classes of DNA subsequences. Each equivalence class includes
      subsequence whose corresponding words on GF(22) are encoded to a corresponding
      code word. The code word is used as a hash key to store these subsequences in a
      hash table. Specifically, it reduces by about 70% the number of hash keys
      necessary for searching the genome positions of all 2-mismatches of 21-base-long
      DNA subsequence. CONCLUSIONS: The paper shows perfect hamming code can reduce the
      number of hash references for hash-based genome mapping. As the computation time
      to calculate code words is far shorter than a hash reference, our method is
      effective to reduce the computation time to map short DNA sequences to genome.
      The amount of data that DNA sequencers generate continues to increase and more
      accurate genome mappings are required. Thus our method will be a key technology
      to develop faster genome mapping software.

PMID- 22369458
TI  - Neuroprotection by mefenamic acid against D-serine: involvement of oxidative
      stress, inflammation and apoptosis.
AB  - Mefenamic acid, a non-steroidal antiinflammatory drug (NSAID), directly and dose
      dependently exhibits neuroprotective activity. In our study, we investigated the
      effects of mefenamic acid against d-serine on oxidative stress in the
      hippocampus, cortex and cerebellum of rats. Furthermore, the potential
      inflammatory and apoptotic effects of d-serine and potential protective effect of
      mefenamic acid were determined at mRNA and protein levels of TNF-alpha, IL-1beta,
      Bcl-2 and Bax. We found that d-serine significantly increased oxidative stress,
      levels of inflammation- and apoptosis-related molecules in a region specific
      manner. Mefenamic acid treatment provided significant protection against the
      elevation of lipid peroxidation, protein oxidation, levels of TNF-alpha, IL-1beta
      and Bax. As a conclusion, we suggest that d-serine, as a potential
      neurodegenerative agent, may have a pivotal role in the regulation of oxidative
      stress, inflammation and apoptosis; and NSAIDs, such as mefenamic acid, may
      assist other therapeutics in treating disorders where d-serine-induced neurotoxic
      mechanisms are involved in.

PMID- 22369459
TI  - A hidden Markov model-based algorithm for identifying tumour subtype using array
      CGH data.
AB  - BACKGROUND: The recent advancement in array CGH (aCGH) research has significantly
      improved tumor identification using DNA copy number data. A number of
      unsupervised learning methods have been proposed for clustering aCGH samples. Two
      of the major challenges for developing aCGH sample clustering are the high
      spatial correlation between aCGH markers and the low computing efficiency. A
      mixture hidden Markov model based algorithm was developed to address these two
      challenges. RESULTS: The hidden Markov model (HMM) was used to model the spatial
      correlation between aCGH markers. A fast clustering algorithm was implemented and
      real data analysis on glioma aCGH data has shown that it converges to the optimal
      cluster rapidly and the computation time is proportional to the sample size.
      Simulation results showed that this HMM based clustering (HMMC) method has a
      substantially lower error rate than NMF clustering. The HMMC results for glioma
      data were significantly associated with clinical outcomes. CONCLUSIONS: We have
      developed a fast clustering algorithm to identify tumor subtypes based on DNA
      copy number aberrations. The performance of the proposed HMMC method has been
      evaluated using both simulated and real aCGH data. The software for HMMC in both
      R and C++ is available in ND INBRE website
      http://ndinbre.org/programs/bioinformatics.php.

PMID- 22369460
TI  - Intrusion, avoidance, and daily negative affect among couples coping with
      prostate cancer: a dyadic investigation.
AB  - In the present study we examined how husbands' and wives' intrusive thoughts of
      prostate cancer (i.e., thinking about it when not meaning to) and avoidance
      (i.e., efforts to not think about cancer) related to their own and each other's
      average negative affect over a subsequent 14-day period. We examined whether
      congruence or similarity in intrusion about illness, but not avoidance, would be
      associated with less negative affect as this response to cancer could potentially
      facilitate adjustment. Fifty-nine husbands and wives completed measures of
      intrusion and avoidance after the diagnosis of prostate cancer and reported on
      their daily negative affect for 14 days. Using the actor-partner interdependence
      model, both patients and their wives who had high levels of intrusive thoughts
      experienced less negative affect when the other member of the couple also
      experienced high levels of intrusive thoughts. Those who had higher levels of
      avoidance had spouses who had higher levels of negative affect regardless of
      their own levels of avoidance. Congruence in responses to cancer may be adaptive
      for intrusion but not avoidance because the use of intrusive thoughts by both
      husbands and wives can allow couples to process the diagnosis of cancer,
      facilitating psychological adjustment, whereas avoidance does not. The current
      investigation adds to our understanding of how people within a marital dyad
      affect each other as they adjust to a cancer diagnosis.

PMID- 22369461
TI  - Examining impelling and disinhibiting factors for intimate partner violence in
      veterans.
AB  - We examined correlates of intimate partner violence (IPV) in a military Veteran
      sample (N = 129) using Finkel's (2007) framework for understanding the
      interactions between impelling and disinhibiting risk factors. Correlates
      investigated included head contact events (HCEs), posttraumatic stress disorder
      (PTSD) symptoms, and antisocial features. Results indicated that antisocial
      features were significantly associated with IPV at the bivariate level. PTSD
      symptoms also were associated with IPV, but this association was marginally
      significant. Tests of moderation provided support for the expectation that HCEs
      would potentiate associations between antisocial features and IPV. HCEs also
      moderated the association between PTSD symptoms and IPV. However, contrary to
      expectations, the opposite pattern emerged such that PTSD symptoms were
      associated with a higher rate of IPV for those without a history of HCEs. Study
      findings have potentially important implications for furthering our understanding
      of the complex etiology of IPV in this population.

PMID- 22369463
TI  - Longitudinal associations between the quality of parent-child interactions and
      children's sleep at preschool age.
AB  - This study aimed to examine the prospective longitudinal links between the
      quality of mother-child and father-child interactions and preschoolers' sleep.
      Three dimensions of maternal interactive behavior were considered using 70 mother
      child dyads, while the quality of father-child interactions was assessed using 41
      of these families. Maternal mind-mindedness was assessed at 12 months during a
      mother-infant free-play sequence, maternal sensitivity was rated at 12 months
      based on observations performed throughout a home visit, maternal autonomy
      support was assessed at 15 months with a 10-min problem-solving situation, and
      the quality of father-child interactions was scored at 18 months, during father
      child free play. Children's sleep was assessed at 3 and 4 years using a sleep
      diary completed by mothers during 3 consecutive days. Results indicated that,
      after controlling for family socioeconomic status and daycare attendance, the
      quality of both mother-infant and father-infant interactions was positively
      related to children's percentage of night-time sleep at preschool age. These
      findings add to previous literature in suggesting that early caregiving behavior
      by both mothers and fathers is related to subsequent child sleep.

PMID- 22369462
TI  - Eye of the beholder: the individual and dyadic contributions of empathic accuracy
      and perceived empathic effort to relationship satisfaction.
AB  - This study examined links between two distinct facets of empathy-empathic
      accuracy and perceived empathic effort-and one's own and one's partner's
      relationship satisfaction. Using a video recall procedure, participants (n = 156
      couples in committed relationships) reported on their own emotions and their
      perceptions of partners' emotions and partners' empathic intentions during
      moments of high affect in laboratory-based discussions of upsetting events.
      Partners' data were correlated as a measure of how accurately they were able to
      read what the other was feeling and to what degree they felt the other was trying
      to be empathic at those moments. The perception of empathic effort by one's
      partner was more strongly linked with both men's and women's relationship
      satisfaction than empathic accuracy. Men's relationship satisfaction was related
      to the ability to read their partners' positive emotions accurately, whereas
      women's relationship satisfaction was related to their partners' ability to read
      women's negative emotions accurately. Women's ability to read their husbands'
      negative emotions was positively linked to both men's and women's relationship
      satisfaction. Findings suggest that the perception of a partner's empathic effort
      as distinct from empathic accuracy-is uniquely informative in understanding how
      partners may derive relationship satisfaction from empathic processes. When
      working with couples in treatment, heightening partners' perceptions of each
      other's empathic effort, and helping partners learn to demonstrate effort, may
      represent particularly powerful opportunities for improving satisfaction in
      relationships.

PMID- 22369464
TI  - Low-income mothers' patterns of partnership instability and adolescents'
      socioemotional well-being.
AB  - The present study investigated the association of family structure and maternal
      partnership instability patterns with adolescents' behavioral and emotional well
      being among urban low-income families. Analyses employed data from the Three-City
      Study to track maternal partnerships over the youth's life span, linking
      longitudinal family structure and transition patterns to adolescent well-being (N
      = 2305). Families were classified into nine mutually exclusive longitudinal
      partnership groups based on current status at wave 3 (single, married, or
      cohabiting) and the longevity of that status: always (since adolescent's birth
      with no transitions), stable (lasting two years or more, preceded by
      transitions), or new (transpiring in the past 2 years). Adolescents in the always
      married group displayed less delinquency and externalizing problems, according to
      both youth and mother reports, than peers in always single-parent or newly
      married households. In contrast, youth in always cohabiting households had higher
      maternal ratings of internalizing problems and youth with newly cohabiting
      mothers reported higher psychological distress than peers in similar stability
      groups with single or married mothers. Overall, several potential explanatory
      processes for the family structure and stability patterns surfaced: married
      parent families reported less economic hardship, more family routines and father
      involvement, and less maternal psychological distress and parenting stress than
      their single and cohabiting counterparts. Policy implications of these findings
      are discussed.

PMID- 22369465
TI  - Associations between atopic markers in asthma and intestinal helminth infections
      in Cuban schoolchildren.
AB  - Total serum IgE (tIgE), allergen-specific IgE (sIgE), and skin prick test (SPT)
      are commonly used markers for atopy and atopic disease. The association between
      these measures and their relationship to clinical symptoms differs in affluent
      and non-affluent countries. We investigated the role of intestinal helminth
      infections in observed variations in atopic markers and asthma, and possible
      diagnostic and epidemiological consequences. A cross-sectional study was
      conducted in Cuban schoolchildren (n = 1285; 4-14 yrs). Atopy was determined by
      SPT, sIgE, and tIgE; asthma by International Study of Asthma and Allergies in
      Childhood questionnaire; and intestinal helminth infections by stool examination.
      Percentages of tIgE, sIgE, and SPT positives were 88.9%, 25.5%, and 16.5%,
      respectively. Asthma was found in 20.8%, and helminth infections in 20.9% of the
      children. All three atopic markers were significantly associated with each other
      and with asthma. Median tIgE levels were higher in helminth-infected than in
      uninfected children, irrespective of their status of atopy/asthma. Discordant
      results between SPT and sIgE were observed in 22.6% of the children. Among SPT
      positives, 41% were sIgE negative. The proportion of SPT negatives among sIgE
      positives was 74% in helminth-infected and 58.4% in uninfected children (p <
      0.05). Helminth infections affected tIgE levels, reconfirming the limited value
      of tIgE for diagnosis of atopy and asthma in tropical areas. Higher frequencies
      of sIgE than positive SPTs were observed, especially in helminth-infected
      children. This corresponds with current hypothesis on the role of helminths in
      atopy. However, the observed proportion of sIgE negatives among children with
      positive SPT suggests that other mechanisms may also be involved.

PMID- 22369466
TI  - Logic operations of chemically assembled single-electron transistor.
AB  - Double-gate single-electron transistors (SETs) were fabricated by chemical
      assembling using electroless gold-plated nanogap electrodes and chemisorbed
      chemically synthesized gold nanoparticles. The fabricated SET showed periodic and
      stable Coulomb oscillations under application of voltages of both gates. The sole
      SET also exhibited all two-input logic operations-XOR, XNOR, NAND, OR, NOR, and
      AND-with an on/off ratio of 10(2). This demonstrates the potential of chemical
      assembling to give highly stable SETs exhibiting all logic operations.

PMID- 22369467
TI  - The impacts of deacetylation prior to dilute acid pretreatment on the bioethanol
      process.
AB  - BACKGROUND: Dilute acid pretreatment is a promising pretreatment technology for
      the biochemical production of ethanol from lignocellulosic biomass. During dilute
      acid pretreatment, xylan depolymerizes to form soluble xylose monomers and
      oligomers. Because the xylan found in nature is highly acetylated, the formation
      of xylose monomers requires two steps: 1) cleavage of the xylosidic bonds, and 2)
      cleavage of covalently bonded acetyl ester groups. RESULTS: In this study, we
      show that the latter may be the rate limiting step for xylose monomer formation.
      Furthermore, acetyl groups are also found to be a cause of biomass recalcitrance
      and hydrolyzate toxicity. While the removal of acetyl groups from native corn
      stover by alkaline de-esterification prior to pretreatment improves overall
      process yields, the exact impact is highly dependent on the corn stover variety
      in use. Xylose monomer yields in pretreatment generally increases by greater than
      10%. Compared to pretreated corn stover controls, the deacetylated corn stover
      feedstock is approximately 20% more digestible after pretreatment. Finally, by
      lowering hydrolyzate toxicity, xylose utilization and ethanol yields are further
      improved during fermentation by roughly 10% and 7%, respectively. In this study,
      several varieties of corn stover lots were investigated to test the robustness of
      the deacetylation-pretreatment-saccharification-fermentation process.
      CONCLUSIONS: Deacetylation shows significant improvement on glucose and xylose
      yields during pretreatment and enzymatic hydrolysis, but it also reduces
      hydrolyzate toxicity during fermentation, thereby improving ethanol yields and
      titer. The magnitude of effect is dependent on the selected corn stover variety,
      with several varieties achieving improvements of greater than 10% xylose yield in
      pretreatment, 20% glucose yield in low solids enzymatic hydrolysis and 7% overall
      ethanol yield.

PMID- 22369468
TI  - CD10 is expressed in nail mesenchyme (onychodermis) containing onychofibroblasts
      of the adult nail unit.

PMID- 22369470
TI  - Growth of large-area and highly crystalline MoS2 thin layers on insulating
      substrates.
AB  - The two-dimensional layer of molybdenum disulfide (MoS(2)) has recently attracted
      much interest due to its direct-gap property and potential applications in
      optoelectronics and energy harvesting. However, the synthetic approach to obtain
      high-quality and large-area MoS(2) atomic thin layers is still rare. Here we
      report that the high-temperature annealing of a thermally decomposed ammonium
      thiomolybdate layer in the presence of sulfur can produce large-area MoS(2) thin
      layers with superior electrical performance on insulating substrates.
      Spectroscopic and microscopic results reveal that the synthesized MoS(2) sheets
      are highly crystalline. The electron mobility of the bottom-gate transistor
      devices made of the synthesized MoS(2) layer is comparable with those of the
      micromechanically exfoliated thin sheets from MoS(2) crystals. This synthetic
      approach is simple, scalable, and applicable to other transition metal
      dichalcogenides. Meanwhile, the obtained MoS(2) films are transferable to
      arbitrary substrates, providing great opportunities to make layered composites by
      stacking various atomically thin layers.

PMID- 22369471
TI  - Role of the D-loops in allosteric control of ATP hydrolysis in an ABC
      transporter.
AB  - ABC transporters couple ATP hydrolysis to movement of substrates across cell
      membranes. They comprise two transmembrane domains and two cytosolic nucleotide
      binding domains forming two active sites that hydrolyze ATP cooperatively. The
      mechanism of ATP hydrolysis is controversial and the structural dynamic basis of
      its allosteric control unknown. Here we report molecular dynamics simulations of
      the ATP/apo and ATP/ADP states of the bacterial ABC exporter Sav1866, in which
      the cytoplasmic region of the protein was simulated in explicit water for 150 ns.
      In the simulation of the ATP/apo state, we observed, for the first time,
      conformers of the active site with the canonical geometry for an in-line
      nucleophilic attack on the ATP gamma-phosphate. The conserved glutamate
      immediately downstream of the Walker B motif is the catalytic base, forming a
      dyad with the H-loop histidine, whereas the Q-loop glutamine has an organizing
      role. Each D-loop provides a coordinating residue of the attacking water, and
      comparison with the simulation of the ATP/ADP state suggests that via their
      flexibility, the D-loops modulate formation of the hydrolysis-competent state. A
      global switch involving a coupling helix delineates the signal transmission route
      by which allosteric control of ATP hydrolysis in ABC transporters is mediated.

PMID- 22369472
TI  - Hydrazone as the directing group for Ir-catalyzed arene diborylations and
      sequential functionalizations.
AB  - The use of hemilabile pyridine-hydrazone N,N-ligands allows the highly selective
      Ir-catalyzed ortho,ortho'-directed diborylation of aromatic N,N
      dimethylhydrazones in near-quantitative yields. One-pot sequential Suzuki-Miyaura
      cross-coupling with different aryl bromides provides a short entry to
      unsymmetrically substituted 2,6-diarylbenzaldehyde derivatives.

PMID- 22369473
TI  - Punctate white matter lesions in a late preterm-born infant with hypoxic
      ischaemic encephalopathy: chronological change in magnetic resonance imaging.

PMID- 22369474
TI  - Socio-economic risk factors for incident restless legs syndrome in the general
      population.
AB  - Few and controversial data exist about the relationship between socio-economic
      status and restless legs syndrome, and prospective analyses are lacking. We aimed
      to explore the associations between socio-economic factors and incident restless
      legs syndrome in the general population. Two prospective population-based cohort
      studies were conducted: the Dortmund Health Study with a mean follow-up of 2.2
      years; and the Study of Health in Pomerania with a mean follow-up of 5.2 years.
      The studies included 1312 subjects and 4308 subjects, respectively. Restless legs
      syndrome was assessed twice according to the standard minimal criteria. The
      modified Winkler Index of social class, education, job status, partnership and
      income were assessed by interviews at baseline. The risk of restless legs
      syndrome associated with each socio-economic factor was estimated by
      multivariable logistic regression adjusted for behavioural factors and co
      morbidities. Female gender, being retired and unemployment were independent risk
      factors of incident restless legs syndrome in both studies. Low level of
      education and income were independently associated with incident restless legs
      syndrome only in the Dortmund Health Study, but not in the other study.
      Migrational background and shiftwork were further independent risk factors of
      restless legs syndrome that were only assessed in the Dortmund Health Study.
      People with less favourable socio-economic situation are at an increased risk of
      developing restless legs syndrome. Behavioural variables and co-morbidities did
      not explain this association, thus further studies are required to reveal the
      mechanism behind the proposed relationship.

PMID- 22369476
TI  - Degradation of cationic red GTL by catalytic wet air oxidation over Mo-Zn-Al-O
      catalyst under room temperature and atmospheric pressure.
AB  - To overcome the drawback of catalytic wet air oxidation (CWAO) with high
      temperature and high pressure, the catalytic activity of Mo-Zn-Al-O catalyst for
      degradation of cationic red GTL under room temperature and atmospheric pressure
      was investigated. Mo-Zn-Al-O catalyst was prepared by coprecipitation and
      impregnation. XRD, TG-DTG, and XPS were used to characterize the resulting
      sample. Central composition design using response surface methodology was
      employed to optimize correlation of factors on the decolorization of cationic red
      GTL. The results show that the optimal conditions of pH value, initial
      concentration of dye and catalyst dosage were found to be 4.0, 85 mg/L and 2.72
      g/L, respectively, for maximum decolorization of 80.1% and TOC removal of 50.9%.
      Furthermore, the reaction on the Mo-Zn-Al-O catalyst and degradation mechanism of
      cationic red GTL was studied by Electron spin resonance (ESR) and GC-MS
      technique. The possible reaction mechanism was that the Mo-Zn-Al-O catalyst can
      efficiently react with adsorbed oxygen/H(2)O to produce .OH and (1)O(2) and
      finally induce the degradation of cationic red GTL. GC-MS analysis of the
      degradation products indicates that cationic red GTL was initiated by the
      cleavage of -N ? N- and the intermediates were further oxidized by .OH or
      (1)O(2).

PMID- 22369478
TI  - trans-Chloro(1-naphthyl)bis(triphenylphosphine)nickel(II)/PCy3 catalyzed cross
      coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl
      mesylates and sulfamates at room temperature.
AB  - trans-Chloro(1-naphthyl)bis(triphenylphosphine)nickel(II) complex/PCy(3) system
      has been successfully applied as catalyst for the Suzuki-Miyaura cross-coupling
      of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl
      mesylates and sulfamates in THF at room temperature. This cross-coupling reaction
      tolerates various functional groups, including keto, imino, ester, ether, and
      cyano. Together with the nickel-catalyzed, one-pot, two-step
      neopentylglycolborylation, this bench stable and inexpensive Ni(II)-based
      catalyst can be utilized as an alternative to Ni(COD)(2)/PCy(3) to provide an
      inexpensive, robust, and convenient synthesis of biaryl and heterobiaryl
      compounds.

PMID- 22369477
TI  - Interrogation of alternative splicing events in duplicated genes during
      evolution.
AB  - BACKGROUND: Gene duplication provides resources for developing novel genes and
      new functions while retaining the original functions. In addition, alternative
      splicing could increase the complexity of expression at the transcriptome and
      proteome level without increasing the number of gene copy in the genome.
      Duplication and alternative splicing are thought to work together to provide the
      diverse functions or expression patterns for eukaryotes. Previously, it was
      believed that duplication and alternative splicing were negatively correlated and
      probably interchangeable. RESULTS: We look into the relationship between
      occurrence of alternative splicing and duplication at different time after
      duplication events. We found duplication and alternative splicing were indeed
      inversely correlated if only recently duplicated genes were considered, but they
      became positively correlated when we took those ancient duplications into
      account. Specifically, for slightly or moderately duplicated genes with gene
      families containing 2 - 7 paralogs, genes were more likely to evolve alternative
      splicing and had on average a greater number of alternative splicing isoforms
      after long-term evolution compared to singleton genes. On the other hand, those
      large gene families (contain at least 8 paralogs) had a lower proportion of
      alternative splicing, and fewer alternative splicing isoforms on average even
      when ancient duplicated genes were taken into consideration. We also found these
      duplicated genes having alternative splicing were under tighter evolutionary
      constraints compared to those having no alternative splicing, and had an
      enrichment of genes that participate in molecular transducer activities.
      CONCLUSIONS: We studied the association between occurrences of alternative
      splicing and gene duplication. Our results implicate that there are key
      differences in functions and evolutionary constraints among singleton genes or
      duplicated genes with or without alternative splicing incidences. It implies that
      the gene duplication and alternative splicing may have different functional
      significance in the evolution of speciation diversity.

PMID- 22369479
TI  - Alcohol and marijuana use while driving--an unexpected crash risk in Pakistani
      commercial drivers: a cross-sectional survey.
AB  - BACKGROUND: A significant proportion of road traffic crashes are attributable to
      alcohol and marijuana use while driving globally. Sale and use of both substances
      is illegal in Pakistan and is not considered a threat for road traffic injuries.
      However literature hints that this may not be the case. We did this study to
      assess usage of alcohol and marijuana in Pakistani commercial drivers. METHODS: A
      sample of 857 commercial bus and truck drivers was interviewed in October 2008 at
      the largest commercial vehicle station in Rawalpindi and Islamabad, Pakistan.
      Time location cluster sampling was used to select the subjects and a structured
      questionnaire was used to assess the basic demographic profile, substance abuse
      habits of the drivers while on the road, and reasons for usage of illicit
      substances while driving were recorded. Self reported information was collected
      after obtaining informed consent. Chi square and fisher exact tests were used to
      assess differences between groups and logistic regression was used to identify
      significant associations between driver characteristics and alcohol and marijuana
      use. RESULTS: Almost 10% of truck drivers use alcohol while driving on Pakistani
      roads. Marijuana use is almost 30% in some groups. Statistically different
      patterns of usage are seen between population subgroups based on age, ethnicity,
      education, and marital status. Regression analysis shows association of alcohol
      and marijuana use with road rage and error behaviours, and also with an increased
      risk of being involved in road crashes. The reported reasons for using alcohol or
      marijuana show a general lack of awareness of the hazardous nature of this
      practice among the commercial driver population. CONCLUSION: Alcohol and
      marijuana use is highly prevalent in Pakistani commercial drivers. The issue
      needs to be recognized by concerned authorities and methods such as random breath
      tests and sobriety check points need to be employed for proper law enforcement.

PMID- 22369480
TI  - Editorial comment. Prostate-specific antigen response to deferred combined
      androgen blockade therapy using bicalutamide predicts survival after subsequent
      oestrogen and docetaxel therapies in patients with castration-resistant prostate
      cancer.

PMID- 22369481
TI  - A study on promoter characteristics of head-to-head genes in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: Head-to-head (h2h) genes are prone to have association in expression
      and in functionality and have been shown conserved in evolution. Currently there
      are many studies on such h2h gene pairs. We found that the previous studies
      extremely focused on human genome. Furthermore, they only focused on analyses
      that require only gene or protein sequences but not conducted a systematic
      investigation on other promoter features such as the binding evidence of specific
      transcription factors (TFs). This is mainly because of the incomplete resources
      of higher organisms, though they are relatively of interest, than model organisms
      such as Saccharomyces cerevisiae. The authors of this study recently integrated
      nine promoter features of 6603 genes of S. cerevisiae from six databases and five
      papers. These resources are suitable to conduct a comprehensive analysis of h2h
      genes in S. cerevisiae. RESULTS: This study analyzed various promoter features,
      including transcription boundaries (TSS, 5'UTR and 3'UTR), TATA box, TF binding
      evidence, TF regulation evidence, DNA bendability and nucleosome occupancy. The
      expression profiles and gene ontology (GO) annotations were used to measure if
      two genes are associated. Based on these promoter features, we found that i) the
      frequency of h2h genes was close to the expectation, namely they were not
      relatively frequent in genome; ii) the distance between the TSSs of most h2h
      genes fell into the range of 0-600 bps and was more centralized in 0-200 bps of
      the highly associated ones; iii) the number of TFs that regulate both h2h genes
      influenced the co-expression and co-function of the genes, while the number of
      TFs that bind both h2h genes influenced only the co-expression of the genes; iv)
      the association of two h2h genes was influenced by the existence of specific TFs
      such as STP2; v) the association of h2h genes whose bidirectional promoters have
      no TATA box was slightly higher than those who have TATA boxes; vi) the
      association of two h2h genes was not influenced by the DNA bendability and
      nucleosome occupancy. CONCLUSIONS: This study analyzed h2h genes with various
      promoter features that have not been used in analyzing h2h genes. The results can
      be applied to other genomes to confirm if the observations of this study are
      limited to S. cerevisiae or universal in most organisms.

PMID- 22369482
TI  - Overexpression of fibulin-5 in retinal pigment epithelial cells inhibits cell
      proliferation and migration and downregulates VEGF, CXCR4, and TGFB1 expression
      in cocultured choroidal endothelial cells.
AB  - PURPOSE OF THE STUDY: Age-related macular degeneration (AMD) is the most common
      cause of irreversible vision loss. Fibulin-5 (FBLN5) plays a pleiotropic role in
      the pathogenesis of AMD. We examined whether the in vitro overexpression of FBLN5
      in retinal pigment epithelial (RPE) cells alters the proliferation and migration
      of cocultured choroidal endothelial cells (CECs) and explored the possible
      mechanisms involved. MATERIALS AND METHODS: A recombinant lentiviral vector
      carrying the Fbln5 gene was generated to transduce rat RPE cells. The expression
      of FBLN5 in transduced RPE cells was detected by quantitative real-time PCR and
      Western blot. The transduced RPE cells were then cocultured with rhesus macaque
      CECs in a Transwell coculture system. The impact of overexpression of FBLN5 in
      RPE cells on CEC proliferation and migration was assessed, as well as the impact
      on the mRNA expressions of vascular endothelial growth factor (VEGF), C-X-C
      chemokine receptor type 4 (CXCR4), and transforming growth factor beta1 (TGFB1).
      RESULTS: Our results showed that a recombinant lentivirus carrying the Fbln5
      gene, which could induce overexpression of FBLN5 in RPE cells, was successfully
      generated. Overexpression of FBLN5 in RPE cells inhibited cell proliferation and
      migration and downregulated the mRNA expressions of VEGF, CXCR4, and TGFB1 in
      cocultured CECs. CONCLUSIONS: These findings suggest that FBLN5 may interfere
      with choroidal neovascularization by downregulating VEGF, CXCR4, and TGFB1
      expression and inhibiting CEC proliferation and invasion, intensifying interest
      in FBLN5 as a target for therapeutic intervention in neovascular AMD.

PMID- 22369483
TI  - Hydration force between mica surfaces in aqueous KCl electrolyte solution.
AB  - Liquid-vapor molecular dynamics simulations are performed to study the
      interaction forces between two mica surfaces in an aqueous KCl electrolyte
      solution. Strong repulsive hydration force is obtained within a distance of ~2 nm
      between the two mica surfaces, which cannot be explained by the continuum theory
      of double-layer repulsion. We find that this short-range repulsive hydration
      force is much stronger than the double-layer force between mica surfaces. Whereas
      the simulation system is much smaller than the surface force measurement system,
      fundamental mechanisms of repulsive hydration force are revealed. In particular,
      important features of the step-like force oscillatory behavior during normal
      compression and force hysteresis during retraction are observed. Detailed
      analysis of the ionic density distributions shows that the "forced adsorption" of
      diffusive K(+) ions onto mica surfaces during compression and the subsequent
      "slow desorption" of the absorbed K(+) ions from mica surfaces upon retraction
      are responsible for the hysteresis phenomenon. From a mechanics point of view, we
      attribute the load bearing capacity of the dense electrolyte to the very hard
      hydration shells of K(+) metal ions under confinement. We find that the hydrated
      K(+) ions and Cl(-) co-ions remain very diffusive in the aqueous film. Water
      molecules in the hydration layer are also very fluidic, in the sense that the
      diffusion constant of water molecules is less than its bulk value by at most 3
      orders of magnitude under the extreme confinement.

PMID- 22369484
TI  - Near-infrared theranostic photoimmunotherapy (PIT): repeated exposure of light
      enhances the effect of immunoconjugate.
AB  - Armed antibody-based targeted molecular therapies offer the possibility of
      effective tumor control with a minimum of side effects. Photoimmunotherapy (PIT)
      employs a monoclonal antibody-phototoxic phthalocyanine dye, IR700 conjugate,
      that is activated by focal near-infrared (NIR) light irradiation after antibody
      binding to the targeted tumor cell surface leading to rapid necrotic cell death.
      Therapy by single NIR light irradiation was effective without significant side
      effects; however, recurrences were seen in most treated mice probably because of
      inhomogeneous distribution of panitumumab-IR700 immunoconjugate in the tumor,
      leading to ineffective PIT. We describe here an optimized regimen of effective
      PIT method for the same HER1-overexpressing tumor model (A431) with fractionated
      administration of panitumumab-IR700 conjugate followed by systematic repeated NIR
      light irradiation to the tumor based on timing of antibody redistribution into
      the remnant tumor under the guidance of IR700 fluorescence signal. Eighty percent
      of the A431 tumors were eradicated with repeated PIT without apparent side
      effects and survived tumor-free for more than 120 days even after stopping
      therapy at day 30. Therapeutic effects were monitored using IR700 fluorescent
      signal. PIT is a promising highly selective and clinically feasible theranostic
      method for treatment of mAb-binding tumors with minimal off-target effects.

PMID- 22369485
TI  - Electrokinetic flow and electric current in a fibrous porous medium.
AB  - An analytical study is presented for the steady electrokinetic flow of
      electrolyte solutions in the fibrous medium constructed by an ordered array of
      identical, parallel, charged, circular cylinders. The electric field and/or
      pressure gradient are applied uniformly in the direction along the axes of the
      cylinders. The dielectric cylinders may have either a constant surface potential
      or a constant surface charge density of an arbitrary value. The electric double
      layer surrounding each cylinder may have an arbitrary thickness relative to the
      radius of the cylinder. A unit cell model, which allows for the overlap of the
      double layers of adjacent cylinders, is employed to account for the effect of
      fiber interactions. The electrostatic potential distribution in the fluid phase
      is determined by solving the Poisson-Boltzmann equation, and the fluid velocity
      profile is obtained as the analytical solution of a modified Navier-Stokes
      equation. Explicit formulas for the flow rate, electroosmotic velocity, electric
      current, effective electric conductivity, and streaming potential are derived as
      functions of the porosity of the fiber matrix and other characteristics of the
      system. The effect of interactions among the cylinders on the fluid velocity and
      effective conductivity is interesting and can be significant under appropriate
      conditions.

PMID- 22369486
TI  - Facial affect recognition and schizotypal personality characteristics.
AB  - AIM: Deficits in facial affect recognition are well established in schizophrenia,
      yet relatively little research has examined facial affect recognition in
      hypothetically psychosis-prone or 'schizotypal' individuals. Those studies that
      have examined social cognition in psychosis-prone individuals have paid little
      attention to the association between facial emotion recognition and particular
      schizotypal personality features. The present study therefore sought to
      investigate relationships between facial emotion recognition and the different
      aspects of schizotypy. METHODS: Facial affect recognition accuracy was examined
      in 50 psychiatrically healthy individuals assessed for level of schizotypy using
      the Schizotypal Personality Questionnaire. This instrument provides a
      multidimensional measure of schizophrenia proneness, encompassing 'cognitive
      perceptual', 'interpersonal' and 'disorganized' features of schizotypy. It was
      hypothesized that the cognitive-perceptual and interpersonal aspects of
      schizotypy would be associated with difficulties identifying facial expressions
      of emotion during a forced-choice recognition task using a standardized series of
      colour photographs. RESULTS: As predicted, interpersonal aspects of schizotypy
      (particularly social anxiety) were associated with reduced accuracy on the facial
      affect recognition task, but there was no association between affect recognition
      accuracy and cognitive-perceptual features of schizotypy. CONCLUSIONS: These
      results suggest that subtle deficits in facial affect recognition in otherwise
      psychiatrically healthy individuals may be related to the vulnerability for
      interpersonal communication difficulties, as seen in schizophrenia.

PMID- 22369487
TI  - Ependymoma with "granular cell" features: report of two cases.
AB  - We report two cases of ependymoma which showed prominent "granular cell" changes
      of the cytoplasm. The patients were a 7-year-old boy with a tumor in the
      cerebellum (case 1) and a 70-year-old man with a tumor in the frontal lobe (case
      2). The tumor of case 1 showed a histopathological appearance of ependymoma
      containing many focal aggregates of large polygonal cells in which the cytoplasm
      was stuffed with numerous eosinophilic granules. The tumor of case 2
      predominantly showed the features of papillary ependymoma, and some tumor cells
      were swollen and contained similar eosinophilic granules. Intracytoplasmic
      granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for
      epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were
      found as aggregates of membrane-bound, electron-dense, globular structures.
      Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies.
      Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and
      oligodendroglial neoplasms, but an appearance of similar granules is very rare in
      ependymoma. The two cases presented here may represent a new histopathological
      variant of ependymoma, and the term "granular cell ependymoma" is appropriate for
      them.

PMID- 22369489
TI  - Gallstone disease is associated with rectal cancer: a meta-analysis.
AB  - BACKGROUND: Increased levels of secondary bile acids after cholecystectomy and
      cholelithiasis are believed to increase the risk of colorectal cancer, and
      several studies have suggested that the risk of colorectal cancer may be the
      greatest proximally. Numerous conflicting studies have been published and it
      remains unclear whether the risk is apparent in the rectum. This meta-analysis
      aims to determine the risk of developing rectal cancer following gallstone
      disease or cholecystectomy. METHODS: The prospective protocol included a
      literature search of PubMed, MEDLINE, EMBASE, and Current Contents (1950-2011).
      Selection criteria were developed to sort for studies exploring the relationship
      between cholelithiasis, cholecystectomy, and rectal cancer in an adult
      population. A random-effects model was used to generate pooled odds ratios (OR)
      and 95% confidence intervals (CI). Publication bias and heterogeneity were
      assessed. RESULTS: Of the 2358 studies identified, 42 were suitable for final
      analysis. There were 1,547,506 subjects in total, 14,226 diagnosed with rectal
      cancer, and 496,552 with gallstones or cholecystectomy. There was a statistically
      significant risk of rectal cancer following cholelithiasis (OR = 1.33; 95% CI =
      1.02-1.73), though no risk was apparent following cholecystectomy (OR = 1.14; 95%
      CI = 0.92-1.41). CONCLUSIONS: Cholelithiasis increases the risk of rectal cancer.
      No association exists between cholecystectomy and rectal cancer.

PMID- 22369488
TI  - Purification of polyhydroxybutyrate synthase from its native organism, Ralstonia
      eutropha: implications for the initiation and elongation of polymer formation in
      vivo.
AB  - Class I polyhydroxybutyrate (PHB) synthase (PhaC) from Ralstonia eutropha
      catalyzes the formation of PHB from (R)-3-hydroxybutyryl-CoA, ultimately
      resulting in the formation of insoluble granules. Previous mechanistic studies of
      R. eutropha PhaC, purified from Escherichia coli (PhaC(Ec)), demonstrated that
      the polymer elongation rate is much faster than the initiation rate. In an effort
      to identify a factor(s) from the native organism that might prime the synthase
      and increase the rate of polymer initiation, an N-terminally Strep2-tagged phaC
      (Strep2-PhaC(Re)) was constructed and integrated into the R. eutropha genome in
      place of wild-type phaC. Strep2-PhaC(Re) was expressed and purified by affinity
      chromatography from R. eutropha grown in nutrient-rich TSB medium for 4 h (peak
      production PHB, 15% cell dry weight) and 24 h (PHB, 2% cell dry weight). Analysis
      of the purified PhaC by size exclusion chromatography, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and gel permeation chromatography revealed
      that it unexpectedly copurified with the phasin protein, PhaP1, and with soluble
      PHB (M(w) = 350 kDa) in a "high-molecular weight" (HMW) complex and in
      monomeric/dimeric (M/D) forms with no associated PhaP1 or PHB. Assays for
      monitoring the formation of PHB in the HMW complex showed no lag phase in CoA
      release, in contrast to M/D forms of PhaC(Re) (and PhaC(Ec)), suggesting that
      PhaC in the HMW fraction has been isolated in a PHB-primed form. The presence of
      primed and nonprimed PhaC suggests that the elongation rate for PHB formation is
      also faster than the initiation rate in vivo. A modified micelle model for
      granule genesis is proposed to accommodate the reported observations.

PMID- 22369490
TI  - Walking drawings and walking ability in children with cerebral palsy.
AB  - OBJECTIVES: To investigate whether drawings of the self walking by children with
      cerebral palsy (CP) were associated with walking ability and illness perceptions.
      METHOD: This was an exploratory study in 52 children with CP (M:F = 28:24), mean
      age 11.1 years (range 5-18), who were attending tertiary level outpatient
      clinics. Children were asked to draw a picture of themselves walking. Drawing
      size and content was used to investigate associations with clinical walk tests
      and children's own perceptions of their CP assessed using a CP version of the
      Brief Illness Perception Questionnaire. RESULTS: Larger drawings of the self were
      associated with less distance traveled, higher emotional responses to CP, and
      lower perceptions of pain or discomfort, independent of age. A larger self-to
      overall drawing height ratio was related to walking less distance. Drawings of
      the self confined within buildings and the absence of other figures were also
      associated with reduced walking ability. CONCLUSION: Drawing size and content can
      reflect walking ability, as well as symptom perceptions and distress. Drawings
      may be useful for clinicians to use with children with cerebral palsy to aid
      discussion about their condition.

PMID- 22369491
TI  - Day-to-day variability in nap duration predicts medical morbidity in older
      adults.
AB  - OBJECTIVE: The objectives for the present study were to (a) examine within-person
      variability of nap duration and (b) assess how variability in nap duration is
      related to the number of health conditions in a sample of older adults. For
      highly variable behaviors such as sleep, it is important to consider fluctuations
      within the person instead of solely comparing averages of behaviors across
      persons. METHOD: Data were drawn from a previous study examining sleep in 103
      community-dwelling older adults. Subjective estimates of napping behavior were
      obtained from sleep diaries and objective estimates of napping behavior were
      obtained using actigraphy. Both measures were collected for 14 consecutive days.
      The sampled data were aggregated in terms of (a) average daily time spent napping
      and (b) average within-person fluctuations in daily nap duration. The health
      measure consisted of the number of self-reported health conditions. RESULTS: Both
      the objective and subjective measures revealed that there was considerable day-to
      day fluctuation in nap duration and that variability in nap duration, not mean
      duration, uniquely predicted the number of health conditions, b = .03, b* = .26,
      t(100) = 2.71, p = .01. CONCLUSIONS: Duration of napping in older adults is a
      highly variable behavior, fluctuating as much within- as between-persons.
      Furthermore, variability in nap duration from day to day is predictive of greater
      medical morbidity, suggesting that clinicians should assess for inconsistencies
      in nap behavior in addition to duration, frequency, and timing.

PMID- 22369492
TI  - Intrinsic strength and failure behaviors of graphene grain boundaries.
AB  - As one-dimension line defects, grain boundaries (GBs) can affect many intrinsic
      properties of graphene. In this paper, the mechanical properties of 20
      representative graphene grain boundaries were studied using density functional
      theory and molecular dynamics. With different arrangements of the pentagonal and
      heptagonal rings, the grain boundary may remain flat or become inflected up to 72
      degrees . For the flat GBs, the intrinsic tensile strength decreases linearly
      with the formation energy with a maximum value of 93 GPa, close to that of a
      perfect graphene. The intrinsic tensile strength of the inflected GBs is found to
      generally decrease with increasing inflection angle. Stone-Wales transformation
      is identified as the major failure mechanism of graphene GBs at high
      temperatures, whereas the initial fracture site can be either on the boundary
      line or inside the domain. These theoretical results constitute a useful picture
      of the grain boundary effect on the mechanical properties of polycrystalline
      graphene.

PMID- 22369493
TI  - Predicting adverse side effects of drugs.
AB  - BACKGROUND: Studies of toxicity and unintended side effects can lead to improved
      drug safety and efficacy. One promising form of study comes from molecular
      systems biology in the form of "systems pharmacology". Systems pharmacology
      combines data from clinical observation and molecular biology. This approach is
      new, however, and there are few examples of how it can practically predict
      adverse reactions (ADRs) from an experimental drug with acceptable accuracy.
      RESULTS: We have developed a new and practical computational framework to
      accurately predict ADRs of trial drugs. We combine clinical observation data with
      drug target data, protein-protein interaction (PPI) networks, and gene ontology
      (GO) annotations. We use cardiotoxicity, one of the major causes for drug
      withdrawals, as a case study to demonstrate the power of the framework. Our
      results show that an in silico model built on this framework can achieve a
      satisfactory cardiotoxicity ADR prediction performance (median AUC = 0.771,
      Accuracy = 0.675, Sensitivity = 0.632, and Specificity = 0.789). Our results also
      demonstrate the significance of incorporating prior knowledge, including gene
      networks and gene annotations, to improve future ADR assessments. CONCLUSIONS:
      Biomolecular network and gene annotation information can significantly improve
      the predictive accuracy of ADR of drugs under development. The use of PPI
      networks can increase prediction specificity and the use of GO annotations can
      increase prediction sensitivity. Using cardiotoxicity as an example, we are able
      to further identify cardiotoxicity-related proteins among drug target expanding
      PPI networks. The systems pharmacology approach that we developed in this study
      can be generally applicable to all future developmental drug ADR assessments and
      predictions.

PMID- 22369494
TI  - UASIS: Universal Automatic SNP Identification System.
AB  - BACKGROUND: SNP (Single Nucleotide Polymorphism), the most common genetic
      variations between human beings, is believed to be a promising way towards
      personalized medicine. As more and more research on SNPs are being conducted, non
      standard nomenclatures may generate potential problems. The most serious issue is
      that researchers cannot perform cross referencing among different SNP databases.
      This will result in more resources and time required to track SNPs. It could be
      detrimental to the entire academic community. RESULTS: UASIS (Universal Automated
      SNP Identification System) is a web-based server for SNP nomenclature
      standardization and translation at DNA level. Three utilities are available. They
      are UASIS Aligner, Universal SNP Name Generator and SNP Name Mapper. UASIS maps
      SNPs from different databases, including dbSNP, GWAS, HapMap and JSNP etc., into
      an uniform view efficiently using a proposed universal nomenclature and state-of
      art alignment algorithms. UASIS is freely available at http://www.uasis.tk with
      no requirement of log-in. CONCLUSIONS: UASIS is a helpful platform for SNP cross
      referencing and tracking. By providing an informative, unique and unambiguous
      nomenclature, which utilizes unique position of a SNP, we aim to resolve the
      ambiguity of SNP nomenclatures currently practised. Our universal nomenclature is
      a good complement to mainstream SNP notations such as rs# and HGVS guidelines.
      UASIS acts as a bridge to connect heterogeneous representations of SNPs.

PMID- 22369495
TI  - High ion conducting polymer nanocomposite electrolytes using hybrid nanofillers.
AB  - There is a growing shift from liquid electrolytes toward solid polymer
      electrolytes, in energy storage devices, due to the many advantages of the latter
      such as enhanced safety, flexibility, and manufacturability. The main issue with
      polymer electrolytes is their lower ionic conductivity compared to that of liquid
      electrolytes. Nanoscale fillers such as silica and alumina nanoparticles are
      known to enhance the ionic conductivity of polymer electrolytes. Although carbon
      nanotubes have been used as fillers for polymers in various applications, they
      have not yet been used in polymer electrolytes as they are conductive and can
      pose the risk of electrical shorting. In this study, we show that nanotubes can
      be packaged within insulating clay layers to form effective 3D nanofillers. We
      show that such hybrid nanofillers increase the lithium ion conductivity of PEO
      electrolyte by almost 2 orders of magnitude. Furthermore, significant improvement
      in mechanical properties were observed where only 5 wt % addition of the filler
      led to 160% increase in the tensile strength of the polymer. This new approach of
      embedding conducting-insulating hybrid nanofillers could lead to the development
      of a new generation of polymer nanocomposite electrolytes with high ion
      conductivity and improved mechanical properties.

PMID- 22369496
TI  - Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female
      mice--a model of human filamin A (FLNA) diseases.
AB  - BACKGROUND: Some abnormalities of mouse corneal epithelial maintenance can be
      identified by the atypical mosaic patterns they produce in X-chromosome
      inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X
      linked, filamin A gene (FLNA) mutations, display a range of disorders and X
      inactivation mosaicism is sometimes quantitatively unbalanced. FlnaDilp2/+ mice,
      heterozygous for an X-linked filamin A (Flna) nonsense mutation have variable
      eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been
      investigated. The aim of this study was to determine whether X-inactivation
      mosaicism in the corneal epithelia of FlnaDilp2/+ mice was affected in any way
      that might predict abnormal corneal epithelial maintenance. RESULTS: X-chromosome
      inactivation mosaicism was studied in the corneal epithelium and a control tissue
      (liver) of FlnaDilp2/+ and wild-type (WT) female X-inactivation mosaics,
      hemizygous for the X-linked, LacZ reporter H253 transgene, using beta
      galactosidase histochemical staining. The corneal epithelia of FlnaDilp2/+ and WT
      X-inactivation mosaics showed similar radial, striped patterns, implying
      epithelial cell movement was not disrupted in FlnaDilp2/+ corneas. Corrected
      stripe numbers declined with age overall (but not significantly for either
      genotype individually), consistent with previous reports suggesting an age
      related reduction in stem cell function. Corrected stripe numbers were not
      reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was
      not significantly more unbalanced in the corneal epithelia or livers of
      FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. CONCLUSIONS: Mosaic
      analysis identified no major effect of the mouse FlnaDilp2 mutation on corneal
      epithelial maintenance or the balance of X-inactivation mosaicism in the corneal
      epithelium or liver.

PMID- 22369498
TI  - Duration of recognized fever in febrile seizure predicts later development of
      epilepsy.
AB  - BACKGROUND: The current report examines the risk of and predictors for developing
      epilepsy in children with febrile seizure (FS). The present study addresses two
      factors that were previously identified as predictors of recurrent FS in previous
      reports: maximum temperature and duration of fever prior to the initial FS.
      METHODS: Children aged 6 months-6 years with an initial simple FS were eligible
      for the study. The interview included questions about the child's illness, family
      history of seizures, and other exposure information. In particular, they were
      asked about the duration of recognized fever prior to the seizure. After the
      initial interview, parents were called every 3-4 months to ascertain whether any
      further seizures had occurred and the circumstances under which such seizures
      occurred. Follow up >= 3 years was attempted for all children. Statistical
      analysis was done with chi(2) test, Fisher's exact test, Mann-Whitney U-tests and
      logistic regression analysis. RESULTS: Five of 92 children (5.4%) experienced
      unprovoked seizures and were considered part of an epilepsy group. In four of
      these five patients, the duration of recognized fever prior to FS fell more than
      +/- 2.5 SD outside the distribution for the non-epilepsy group. Either an
      unusually short or long recognized fever prior to the initial FS was associated
      with an increased risk of unprovoked seizures. CONCLUSIONS: The duration of
      recognized fever appears to provide useful information about the risk for the
      later development of epilepsy.

PMID- 22369499
TI  - Pruritic axillary papules.

PMID- 22369497
TI  - Female genital tract shedding of CXCR4-tropic HIV Type 1 is associated with a
      majority population of CXCR4-tropic HIV Type 1 in blood and declining CD4(+) cell
      counts.
AB  - This study compared HIV-1 genotypes shed over time (<=3.5 years) in the vaginal
      secretions (VS) and blood plasma (BP) of 15 chronically infected women. Analysis
      of predicted coreceptor tropism (CCR5=R5, CXCR4=X4) for quasispecies shedding
      revealed three patterns: (1) viral quasispecies shed in both VS and BP were
      restricted to R5-tropism at all time points, (2) quasispecies shed in VS were
      restricted to R5-tropism at all time points but X4 quasispecies were identified
      in the BP at one or more time points, and (3) quasispecies shed in matched VS and
      BP both contained X4-tropic viruses. Overall, the frequency of X4 quasispecies
      circulation in VS was 2-fold less than in BP and detection of X4 virus in VS was
      more likely to occur when X4 quasispecies comprised more than 50% of BP viruses
      (p=0.01) and when declines in blood CD4(+) lymphocyte levels were the greatest
      (p=0.038). Additionally, the mean number of predicted N-glycosylation sites
      between matched VS and BP samples was strongly correlated (r=0.86, p<0.0001) with
      glycosylation densities in the following order (VS R5=BP R5 > BP X4 > VS X4). The
      X4 glycosylation densities may result from compartmentalization pressures in the
      female genital tract or the delayed appearance of these viruses in VS. Our
      results suggest that the presence of X4 virus in VS is associated with a
      threshold population of X4 quasispecies in BP, which are increasing during the
      HIV-induced failure of the human immune system.

PMID- 22369500
TI  - Morphology control of cadmium selenide nanocrystals: insights into the roles of
      di-n-octylphosphine oxide (DOPO) and ucid (DOPA).
AB  - Di-n-octylphosphine oxide (DOPO) and di-n-octylphosphinic acid (DOPA), as two of
      impurities found in commercial tri-n-octylphosphine oxide (TOPO), generate
      significant differences in the outcomes of CdSe-nanocrystal (NC) syntheses. Using
      n-tetradecylphosphonic acid (TDPA) as the primary acid additive, quantum dots
      (QDs) are grown with DOPO added, whereas quantum rods (QRs) are grown in the
      presence of DOPA. While using oleic acid (OA) as the primary acid additive, QDs
      are generated and the QDs produced with DOPA exhibit larger sizes and size
      distributions than those produced with DOPO. (31)P NMR analyses of the reaction
      mixtures reveal that the majority of the DOPO has been converted into DOPA and di
      n-octylphosphine (DOP) with DOP being removed via evacuation over the course of
      Cd-precursor preparation. The origin of the puzzling differences in the shape
      control of CdSe NCs in the presence of DOPO and DOPA is elucidated to be the
      small quantity of DOPO present, which liberates DOP during NC synthesis. In the
      presence of DOP, regardless of DOPA, the precursor-conversion kinetics and thus
      the nucleation kinetics are dramatically accelerated, generating a large number
      of nuclei by consuming a significant amount of CdSe nutrients, favoring QD
      growth. Similarly, QD growth is favored by the fast nucleation kinetics in the
      presence of OA, and the broader size distributions of QDs with DOPA are due to a
      second nucleation event initiated by the more stable Cd-di-n-octylphosphinate
      component. In contrast, a slow nucleation event results in the growth of QRs in
      the case of using DOPA and TDPA, where no DOPO or DOP is present. The results,
      thus, demonstrate the important role of precursor-conversion kinetics in the
      control of NC morphologies.

PMID- 22369501
TI  - Persistence of CD30 expression in Hodgkin lymphoma following brentuximab vedotin
      (SGN-35) treatment failure.

PMID- 22369502
TI  - Marburg virus glycoprotein GP2: pH-dependent stability of the ectodomain alpha
      helical bundle.
AB  - Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of
      enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by
      MARV requires fusion between the host cell and viral membranes, a process that is
      mediated by the two subunits of the envelope glycoprotein, GP1 (surface subunit)
      and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed
      that the MARV viral fusion machinery is triggered by host factors and
      environmental conditions found in the endosome. Next, conformational
      rearrangements in the GP2 ectodomain result in the formation of a highly stable
      six-helix bundle; this refolding event provides the energetic driving force for
      membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but
      there is little information available for the MARV glycoproteins. Here we have
      expressed two variants of the MARV GP2 ectodomain in Escherichia coli and
      analyzed their biophysical properties. Circular dichroism indicates that the MARV
      GP2 ectodomain adopts an alpha-helical conformation, and one variant sediments as
      a trimer by equilibrium analytical ultracentrifugation. Denaturation studies
      indicate the alpha-helical structure is highly stable at pH 5.3 (unfolding
      energy, DeltaG(unf,H(2)O), of 33.4 +/- 2.5 kcal/mol and melting temperature,
      T(m), of 75.3 +/- 2.1  degrees C for one variant). Furthermore, we found the
      alpha-helical stability to be strongly dependent on pH, with higher stability
      under lower-pH conditions (T(m) values ranging from ~92  degrees C at pH 4.0 to
      ~38  degrees C at pH 8.0). Mutational analysis suggests two glutamic acid
      residues (E579 and E580) are partially responsible for this pH-dependent
      behavior. On the basis of these results, we hypothesize that the pH-dependent
      folding stability of the MARV GP2 ectodomain provides a mechanism for controlling
      conformational preferences such that the six-helix bundle "postfusion" state is
      preferred under conditions of appropriately matured endosomes.

PMID- 22369503
TI  - Updating the evolutionary history of Carnivora (Mammalia): a new species-level
      supertree complete with divergence time estimates.
AB  - BACKGROUND: Although it has proven to be an important foundation for
      investigations of carnivoran ecology, biology and evolution, the complete species
      level supertree for Carnivora of Bininda-Emonds et al. is showing its age.
      Additional, largely molecular sequence data are now available for many species
      and the advancement of computer technology means that many of the limitations of
      the original analysis can now be avoided. We therefore sought to provide an
      updated estimate of the phylogenetic relationships within all extant Carnivora,
      again using supertree analysis to be able to analyze as much of the global
      phylogenetic database for the group as possible. RESULTS: In total, 188 source
      trees were combined, representing 114 trees from the literature together with 74
      newly constructed gene trees derived from nearly 45,000 bp of sequence data from
      GenBank. The greater availability of sequence data means that the new supertree
      is almost completely resolved and also better reflects current phylogenetic
      opinion (for example, supporting a monophyletic Mephitidae, Eupleridae and
      Prionodontidae; placing Nandinia binotata as sister to the remaining Feliformia).
      Following an initial rapid radiation, diversification rate analyses indicate a
      downturn in the net speciation rate within the past three million years as well
      as a possible increase some 18.0 million years ago; numerous diversification rate
      shifts within the order were also identified. CONCLUSIONS: Together, the two
      carnivore supertrees remain the only complete phylogenetic estimates for all
      extant species and the new supertree, like the old one, will form a key tool in
      helping us to further understand the biology of this charismatic group of
      carnivores.

PMID- 22369505
TI  - Molecular modeling of the dissociation of methane hydrate in contact with a
      silica surface.
AB  - We use constant energy, constant volume (NVE) molecular dynamics simulations to
      study the dissociation of the fully occupied structure I methane hydrate in a
      confined geometry between two hydroxylated silica surfaces between 36 and 41 A
      apart, at initial temperatures of 283, 293, and 303 K. Simulations of the two
      phase hydrate/water system are performed in the presence of silica, with and
      without a 3 A thick buffering water layer between the hydrate phase and silica
      surfaces. Faster decomposition is observed in the presence of silica, where the
      hydrate phase is prone to decomposition from four surfaces, as compared to only
      two sides in the case of the hydrate/water simulations. The existence of the
      water layer between the hydrate phase and the silica surface stabilizes the
      hydrate phase relative to the case where the hydrate is in direct contact with
      silica. Hydrates bound between the silica surfaces dissociate layer-by-layer in a
      shrinking core manner with a curved decomposition front which extends over a 5-8
      A thickness. Labeling water molecules shows that there is exchange of water
      molecules between the surrounding liquid and intact cages in the methane hydrate
      phase. In all cases, decomposition of the methane hydrate phase led to the
      formation of methane nanobubbles in the liquid water phase.

PMID- 22369504
TI  - Chronotype and diurnal patterns of positive affect and affective neural circuitry
      in primary insomnia.
AB  - While insomnia is a well-established risk factor for the initial onset,
      recurrence or relapse of affective disorders, the specific characteristics of
      insomnia that confer risk remain unclear. Patients with insomnia with an evening
      chronotype may be one particularly high-risk group, perhaps due to alterations in
      positive affect and its related affective circuitry. We explored this possibility
      by comparing diurnal patterns of positive affect and the activity of positive
      affect-related brain regions in morning- and evening-types with insomnia. We
      assessed diurnal variation in brain activity via the relative regional cerebral
      metabolic rate of glucose uptake by using [(18) F]fluorodeoxyglucose-positron
      emission tomography during morning and evening wakefulness. We focused on regions
      in the medial prefrontal cortex and striatum, which have been consistently linked
      with positive affect and reward processing. As predicted, chronotypes differed in
      their daily patterns in both self-reported positive affect and associated brain
      regions. Evening-types displayed diurnal patterns of positive affect
      characterized by phase delay and smaller amplitude compared with those of morning
      types with insomnia. In parallel, evening-types showed a reduced degree of
      diurnal variation in the metabolism of both the medial prefrontal cortex and the
      striatum, as well as lower overall metabolism in these regions across both
      morning and evening wakefulness. Taken together, these preliminary findings
      suggest that alterations in the diurnal activity of positive affect-related
      neural structures may underlie differences in the phase and amplitude of self
      reported positive affect between morning and evening chronotypes, and may
      constitute one mechanism for increased risk of mood disorders among evening-type
      insomniacs.

PMID- 22369506
TI  - Functional changes in human peripheral neutrophils in workers with different
      exposure to noxious agents.
AB  - Peripheral neutrophils (PMN) are a useful model to study cell activation and to
      evaluate the multiple stressors' interference with signalling pathways. This
      study aimed to evaluate the effects of different exposure to noxious agents on
      PMN activity by chemiluminescence assays. Two groups of office workers were
      recruited: peripheral whole blood cells and isolated PMNs were analyzed,
      performing intra- and extra-cellular chemiluminescence evaluation to study
      compartmental release of radical species. The exposed group shows a higher
      emission in resting whole blood chemiluminescence than in controls; the
      intracellular chemiluminescence emission in urban employees was increased,
      whereas the extracellular was not affected. After stimulation, the extracellular
      chemiluminescence was decreased in urban employees, whereas the intracellular
      emission did not show differences. We hypothesize that once stimulated, exposed
      subjects' PMNs respond to stimuli less than unexposed: PMNs could be considered
      indicators of chronic exposure to noxious agents.

PMID- 22369507
TI  - Fatal misuse of humidifier disinfectants in Korea: importance of screening risk
      assessment and implications for management of chemicals in consumer products.

PMID- 22369508
TI  - Phagocytized corpora amylacea as a histological hallmark of astrocytic injury in
      neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating and necrotizing
      disorder of the CNS that mainly affects the optic nerve and spinal cord. The
      etiology is still uncertain; however, the discovery of serum anti-aquaporin-4
      (AQP4) autoantibody is becoming the center of attention, and a new hypothesis is
      emerging that NMO is essentially astrocytopathy provoked by this autoantibody. In
      this study, we focused on corpora amylacea (CA), glycoproteinaceous inclusions in
      astrocytic processes. We examined 57 lesions in nine cases of NMO spectrum
      disorder, and demonstrated that CA were phagocytized by macrophages in 42 lesions
      (74%) of eight cases, while phagocytized figures were not seen in unaffected
      areas. Phagocytized CA were frequently encountered in early-phase lesions still
      retaining myelin structures, while fewer or none were found in chronic
      destructive lesions. Moreover, phagocytized CA were significantly smaller in
      diameter than intact ones, and CA were decreased or absent in most lesions
      assessed. These findings suggest the following pathophysiological process: the
      astrocytes are affected at an early phase in NMO, CA are expelled from the
      astrocytes and phagocytized by macrophages finally leading to clearance. A
      phagocytized figure and subsequent loss of CA can be a histological hallmark of
      astrocytic injury of NMO.

PMID- 22369509
TI  - An estimation method for inference of gene regulatory net-work using Bayesian
      network with uniting of partial problems.
AB  - BACKGROUND: Bayesian networks (BNs) have been widely used to estimate gene
      regulatory networks. Many BN methods have been developed to estimate networks
      from microarray data. However, two serious problems reduce the effectiveness of
      current BN methods. The first problem is that BN-based methods require huge
      computational time to estimate large-scale networks. The second is that the
      estimated network cannot have cyclic structures, even if the actual network has
      such structures. RESULTS: In this paper, we present a novel BN-based
      deterministic method with reduced computational time that allows cyclic
      structures. Our approach generates all the combinational triplets of genes,
      estimates networks of the triplets by BN, and unites the networks into a single
      network containing all genes. This method decreases the search space of
      predicting gene regulatory networks without degrading the solution accuracy
      compared with the greedy hill climbing (GHC) method. The order of computational
      time is the cube of number of genes. In addition, the network estimated by our
      method can include cyclic structures. CONCLUSIONS: We verified the effectiveness
      of the proposed method for all known gene regulatory networks and their
      expression profiles. The results demonstrate that this approach can predict
      regulatory networks with reduced computational time without degrading the
      solution accuracy compared with the GHC method.

PMID- 22369510
TI  - Alcohol and premature death in Estonian men: a study of forensic autopsies using
      novel biomarkers and proxy informants.
AB  - BACKGROUND: Alcohol makes an important contribution to premature mortality in
      many countries in Eastern Europe, including Estonia. However, the full extent of
      its impact, and the mechanisms underlying it, are challenging issues to research.
      We describe the design and initial findings of a study aimed at investigating the
      association of alcohol with mortality in a large series of forensic autopsies of
      working-age men in Estonia. METHODS: 1299 male deaths aged 25-54 years were
      subject to forensic autopsy in 2008-2009. The routine autopsy protocol was
      augmented by a more systematic inspection of organs, drug testing, assay of liver
      enzymes and novel biomarkers of alcohol consumption (EtG, EtS and PEth), together
      with proxy interviews with next of kin for deaths among men who lived in or close
      to a major town. RESULTS: 595 augmented autopsies were performed. Of these, 66%
      were from external causes (26% suicide, 25% poisoning). 17% were attributed to
      circulatory system diseases and 7% to alcoholic liver disease. Blood alcohol
      concentrations (BAC) of >= 0.2 mg/g were found for 55% of deaths. Interviews were
      conducted with proxy informants for 61% of the subjects who had resided in towns.
      Of these, 28% were reported in the previous year to have been daily or almost
      daily drinkers and 10% had drunk non-beverage alcohols. Blood ethanol and the
      liver enzyme GGT were only associated with daily drinking. However, the novel
      biomarkers showed a more graded response with recent consumption. In contrast,
      the liver enzymes AST and ALT were largely uninformative because of post-mortem
      changes. The presence of extremely high PEth concentrations in some samples also
      suggested post-mortem formation. CONCLUSION: We have shown the feasibility of
      deploying an extended research protocol within the setting of routine forensic
      autopsies that offer scope to deepen our understanding of the alcohol-related
      burden of premature mortality. The most unique feature of the study is the
      information on a wide range of informative alcohol biomarkers, several of which
      have not been used previously in this sort of post-mortem research study. We have
      demonstrated, for the first time, the epidemiological value and validity of these
      novel alcohol biomarkers in post-mortem samples.

PMID- 22369511
TI  - Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of
      plantar warts: economic evaluation alongside a randomised controlled trial (EVerT
      trial).
AB  - BACKGROUND: Plantar warts (verrucae) are extremely common. Although many will
      spontaneously disappear without treatment, treatment may be sought for a variety
      of reasons such as discomfort. There are a number of different treatments for
      cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being
      two of the most common forms of treatment. To date, no full economic evaluation
      of either salicylic acid or cryotherapy has been conducted based on the use of
      primary data in a pragmatic setting. This paper describes the cost-effectiveness
      analysis which was conducted alongside a pragmatic multicentre, randomised trial
      evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of
      the treatment of plantar warts. METHODS: A cost-effectiveness analysis was
      undertaken alongside a pragmatic multicentre, randomised controlled trial
      assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using
      liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness
      outcomes were expressed as the additional cost required to completely cure the
      plantar warts of one additional patient. A NHS perspective was taken for the
      analysis. RESULTS: Cryotherapy costs on average L101.17 (bias corrected and
      accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week
      time-frame, while there is no additional benefit, in terms of proportion of
      patients healed compared with salicylic acid. CONCLUSIONS: Cryotherapy is more
      costly and no more effective than salicylic acid. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research
      Register N0484189151.

PMID- 22369512
TI  - Solute- and temperature-responsive "smart" grafts and supported membranes formed
      by covalent layer-by-layer assembly.
AB  - Polymers like poly(N-isopropylacrylamide) (PNIPAM) exhibit lower critical
      solution temperature (LCST) behavior. A variety of reports have shown that brush
      grafts of PNIPAM on surfaces exhibit similar temperature responsiveness. We
      recently described an alternative synthetic approach to such surfaces that
      affords surfaces with similar LCST-like behavior. We also noted how such
      surfaces' wettability can change in response to the identity and concentration of
      solutes. Here we show that this synthetic procedure can be extended to glass
      surfaces and to more complex surfaces present in porous glass frits.
      Functionalized glass surfaces exhibit solute-dependent wetting behavior analogous
      to that previously reported. We further show that the resulting responsive
      nanocomposite grafts on such frits exhibit "smart" responsive permeability with a
      greater than 1000-fold difference in permeability to water versus aqueous
      solutions of sodium sulfate. This "smart" permeability is ascribed to the solute
      dependent wettability behavior of the responsive PNIPAM component of the
      nanocomposite graft, which is sensitive both to the identity and concentration of
      the solute anion and to temperature.

PMID- 22369513
TI  - Analysis of 16S rRNA environmental sequences using MEGAN.
AB  - BACKGROUND: Metagenomics is a rapidly growing field of research aimed at studying
      assemblages of uncultured organisms using various sequencing technologies, with
      the hope of understanding the true diversity of microbes, their functions,
      cooperation and evolution. There are two main approaches to metagenomics:
      amplicon sequencing, which involves PCR-targeted sequencing of a specific locus,
      often 16S rRNA, and random shotgun sequencing. Several tools or packages have
      been developed for analyzing communities using 16S rRNA sequences. Similarly, a
      number of tools exist for analyzing randomly sequenced DNA reads. RESULTS: We
      describe an extension of the metagenome analysis tool MEGAN, which allows one to
      analyze 16S sequences. For the analysis all 16S sequences are blasted against the
      SILVA database. The result output is imported into MEGAN, using a synonym file
      that maps the SILVA accession numbers onto the NCBI taxonomy. CONCLUSIONS:
      Environmental samples are often studied using both targeted 16S rRNA sequencing
      and random shotgun sequencing. Hence tools are needed that allow one to analyze
      both types of data together, and one such tool is MEGAN. The ideas presented in
      this paper are implemented in MEGAN 4, which is available from: http://www
      ab.informatik.uni-tuebingen.de/software/megan.

PMID- 22369514
TI  - Can the vector space model be used to identify biological entity activities?
AB  - BACKGROUND: Biological systems are commonly described as networks of entity
      interactions. Some interactions are already known and integrate the current
      knowledge in life sciences. Others remain unknown for long periods of time and
      are frequently discovered by chance. In this work we present a model to predict
      these unknown interactions from a textual collection using the vector space model
      (VSM), a well known and established information retrieval model. We have extended
      the VSM ability to retrieve information using a transitive closure approach. Our
      objective is to use the VSM to identify the known interactions from the
      literature and construct a network. Based on interactions established in the
      network our model applies the transitive closure in order to predict and rank new
      interactions. RESULTS: We have tested and validated our model using a collection
      of patent claims issued from 1976 to 2005. From 266,528 possible interactions in
      our network, the model identified 1,027 known interactions and predicted 3,195
      new interactions. Iterating the model according to patent issue dates,
      interactions found in a given past year were often confirmed by patent claims not
      in the collection and issued in more recent years. Most confirmation patent
      claims were found at the top 100 new interactions obtained from each subnetwork.
      We have also found papers on the Web which confirm new inferred interactions. For
      instance, the best new interaction inferred by our model relates the interaction
      between the adrenaline neurotransmitter and the androgen receptor gene. We have
      found a paper that reports the partial dependence of the antiapoptotic effect of
      adrenaline on androgen receptor. CONCLUSIONS: The VSM extended with a transitive
      closure approach provides a good way to identify biological interactions from
      textual collections. Specifically for the context of literature-based discovery,
      the extended VSM contributes to identify and rank relevant new interactions even
      if these interactions occur in only a few documents in the collection.
      Consequently, we have developed an efficient method for extracting and
      restricting the best potential results to consider as new advances in life
      sciences, even when indications of these results are not easily observed from a
      mass of documents.

PMID- 22369515
TI  - 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA
      inhibitor for PET imaging.
AB  - Urea-based inhibitors of the prostate-specific membrane antigen (PSMA) represent
      low-molecular-weight pepidomimetics showing the ability to image PSMA-expressing
      prostate tumors. The highly efficient, acyclic Ga(III) chelator N,N'-bis [2
      hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'- diacetic acid (HBED-CC) was
      introduced as a lipophilic side chain into the hydrophilic pharmacophore Glu-NH
      CO-NH-Lys which was found favorable to interact with the PSMA "active binding
      site". This report describes the syntheses, in vitro binding analyses, and
      biodistribution data of the radiogallium labeled PSMA inhibitor Glu-NH-CO-NH
      Lys(Ahx)-HBED-CC in comparison to the corresponding DOTA conjugate. The binding
      properties were analyzed using competitive cell binding and enzyme-based assays
      followed by internalization experiments. Compared to the DOTA-conjugate, the HBED
      CC derivative showed reduced unspecific binding and considerable higher specific
      internalization in LNCaP cells. The (68)Ga complex of the HBED-CC ligand
      exhibited higher specificity for PSMA expressing tumor cells resulting in
      improved in vivo properties. (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC showed
      fast blood and organ clearances, low liver accumulation, and high specific uptake
      in PSMA expressing organs and tumor. It could be demonstrated that the PET
      imaging property of a urea-based PSMA inhibitor could significantly be improved
      with HBED-CC.

PMID- 22369517
TI  - Infrared absorption of gaseous benzoyl radical C6H5CO recorded with a step-scan
      Fourier-transform spectrometer.
AB  - A step-scan Fourier-transform infrared spectrometer coupled with a multipass
      absorption cell was utilized to monitor the gaseous transient species benzoyl
      radical, C(6)H(5)CO. C(6)H(5)CO was produced either from photolysis of
      acetophenone, C(6)H(5)C(O)CH(3), at 248 nm or in reactions of phenyl radical
      (C(6)H(5)) with CO; C(6)H(5) was produced on photolysis of C(6)H(5)Br at 248 nm.
      One intense band at 1838 +/- 1 cm(-1), one weak band at 1131 +/- 3 cm(-1), and
      two extremely weak bands at 1438 +/- 5 and 1590 +/- 10 cm(-1) are assigned to the
      C?O stretching (nu(6)), the C-C stretching mixed with C-H deformation (nu(15)),
      the out-of-phase C(1)C(2)C(3)/C(5)C(6)C(1) symmetric stretching (nu(10)), and the
      in-phase C(1)C(2)C(3)/C(4)C(5)C(6) antisymmetric stretching (nu(7)) modes of
      C(6)H(5)CO, respectively. These observed vibrational wavenumbers and relative IR
      intensities agree with those reported for C(6)H(5)CO isolated in solid Ar and
      with values predicted for C(6)H(5)CO with the B3LYP/aug-cc-pVDZ method. The
      rotational contours of the two bands near 1838 and 1131 cm(-1) simulated
      according to rotational parameters predicted with the B3LYP/aug-cc-pVDZ method
      fit satisfactorily with the experimental results. Additional products BrCO,
      C(6)H(5)C(O)Br, and C(6)H(5)C(O)C(6)H(5) were identified in the
      C(6)H(5)Br/CO/N(2) experiments; the kinetics involving C(6)H(5)CO and
      C(6)H(5)C(O)Br are discussed.

PMID- 22369516
TI  - Enhanced polyhydroxybutyrate production in transgenic sugarcane.
AB  - Polyhydroxybutyrate (PHB) is a bacterial polyester that has properties similar to
      some petrochemically produced plastics. Plant-based production has the potential
      to make this biorenewable plastic highly competitive with petrochemical-based
      plastics. We previously reported that transgenic sugarcane produced PHB at levels
      as high as 1.8% leaf dry weight without penalty to biomass accumulation,
      suggesting scope for improving PHB production in this species. In this study, we
      used different plant and viral promoters, in combination with multigene or single
      gene constructs to increase PHB levels. Promoters tested included the maize and
      rice polyubiquitin promoters, the maize chlorophyll A/B-binding protein promoter
      and a Cavendish banana streak badnavirus promoter. At the seedling stage, the
      highest levels of polymer were produced in sugarcane plants when the Cavendish
      banana streak badnavirus promoter was used. However, in all cases, this promoter
      underwent silencing as the plants matured. The rice Ubi promoter enabled the
      production of PHB at levels similar to the maize Ubi promoter. The maize
      chlorophyll A/B-binding protein promoter enabled the production of PHB to levels
      as high as 4.8% of the leaf dry weight, which is approximately 2.5 times higher
      than previously reported levels in sugarcane. This is the first time that this
      promoter has been tested in sugarcane. The highest PHB-producing lines showed
      phenotypic differences to the wild-type parent, including reduced biomass and
      slight chlorosis.

PMID- 22369518
TI  - Palladium-catalyzed Ullmann-type reductive homocoupling of iodoaryl glycosides.
AB  - A catalytic synthesis of novel biaryl-linked divalent glycosides was achieved
      using an electroreductive palladium-catalyzed iodoaryl-iodoaryl coupling
      reaction. This new method was optimized for the synthesis of divalent biaryl
      linked mannopyranosides that was subsequently generalized toward several
      carbohydrate substrates with yields up to 96%.

PMID- 22369519
TI  - Quantum-enhanced tunable second-order optical nonlinearity in bilayer graphene.
AB  - Second order optical nonlinear processes involve the coherent mixing of two
      electromagnetic waves to generate a new optical frequency, which plays a central
      role in a variety of applications, such as ultrafast laser systems, rectifiers,
      modulators, and optical imaging. However, progress is limited in the mid-infrared
      (MIR) region due to the lack of suitable nonlinear materials. It is desirable to
      develop a robust system with a strong, electrically tunable second order optical
      nonlinearity. Here, we demonstrate theoretically that AB-stacked bilayer graphene
      (BLG) can exhibit a giant and tunable second order nonlinear susceptibility
      chi((2)) once an in-plane electric field is applied. chi((2)) can be electrically
      tuned from 0 to ~10(5) pm/V, 3 orders of magnitude larger than the widely used
      nonlinear crystal AgGaSe(2). We show that the unusually large chi((2)) arise from
      two different quantum enhanced two-photon processes thanks to the unique
      electronic spectrum of BLG. The tunable electronic bandgap of BLG adds additional
      tunability on the resonance of chi((2)), which corresponds to a tunable
      wavelength ranging from ~2.6 to ~3.1 MUm for the up-converted photon. Combined
      with the high electron mobility and optical transparency of the atomically thin
      BLG, our scheme suggests a new regime of nonlinear photonics based on BLG.

PMID- 22369523
TI  - Higher debt, lower salaries a continuing concern for grads.

PMID- 22369520
TI  - Publication bias in psychological science: comment on Ferguson and Brannick
      (2012).
AB  - It is well documented that studies reporting statistically significant results
      are more likely to be published than are studies reporting nonsignificant results
      -a phenomenon called publication bias. Publication bias in meta-analytic reviews
      should be identified and reduced when possible. Ferguson and Brannick (2012)
      argued that the inclusion of unpublished articles is ineffective and possibly
      counterproductive as a means of reducing publication bias in meta-analyses. We
      show how idiosyncratic choices on the part of Ferguson and Brannick led to an
      erroneous conclusion. We demonstrate that their key finding--that publication
      bias was more likely when unpublished studies were included--may be an artifact
      of the way they assessed publication bias. We also point out how the lack of
      transparency about key choices and the absence of information about critical
      features of Ferguson and Brannick's sample and procedures might have obscured
      readers' ability to assess the validity of their claims. Furthermore, we
      demonstrate that many of the claims they made are without empirical support, even
      though they could have tested these claims empirically, and that these claims may
      be misleading. With their claim that addressing publication bias introduces
      subjectivity and bias into meta-analysis, they ignored a large body of evidence
      showing that including unpublished studies that meet the inclusion criteria of a
      meta-analysis decreases (rather than increases) publication bias. Rather than
      exclude unpublished studies, we recommend that meta-analysts code study
      characteristics related to methodological quality (e.g., experimental vs.
      nonexperimental design) and test whether these factors influence the meta
      analytic results.

PMID- 22369524
TI  - Effect of nitrous oxide on the minimum alveolar concentration for sevoflurane and
      the minimum alveolar concentration derivatives that prevent motor movement and
      autonomic responses in dogs.
AB  - OBJECTIVE: To investigate the effects of the concurrent administration of 70%
      N(2)O on the minimum alveolar concentration (MAC) for sevoflurane in dogs, the
      MAC derivative that blocks motor movement (MAC(NM)), and the MAC derivative that
      blocks autonomic responses (MAC(BAR)). ANIMALS: 7 adult sexually intact male
      mixed-breed dogs. PROCEDURES: For each dog, anesthesia was induced with
      sevoflurane delivered via a face mask. Initially, the baseline MAC, MAC(NM), and
      MAC(BAR) for sevoflurane were determined by use of a noxious stimulus (50 V, 50
      Hz, and 10 milliseconds) applied subcutaneously over a midulnar region. Nitrous
      oxide (70%) was added to the breathing circuit, and MAC, MAC(NM), and MAC(BAR)
      were determined again. Percentage changes from the respective baseline
      concentrations for MAC, MAC(NM)' and MAC(BAR) were calculated after the
      administration of N(2)O. RESULTS: Baseline median values for the MAC, MAC(NM),
      and MAC(BAR) for sevoflurane were 1.75%, 2.00%, and 2.50%, respectively. Addition
      of 70% N(2)O significantly decreased MAC, MAC(NM), and MAC(BAR) by 24.4%, 25.0%,
      and 35.2%, respectively, and these values did not differ significantly from each
      other. CONCLUSIONS AND CLINICAL RELEVANCE: Supplementation with 70% N(2)O caused
      a clinically important and significant decrease in the MAC, MAC(NM)' and MAC(BAR)
      for sevoflurane in dogs.

PMID- 22369525
TI  - Evaluation of infusions of xylazine with ketamine or propofol to modulate
      recovery following sevoflurane anesthesia in horses.
AB  - OBJECTIVE: To determine whether infusion of xylazine and ketamine or xylazine and
      propofol after sevoflurane administration in horses would improve the quality of
      recovery from anesthesia. ANIMALS: 6 healthy adult horses. PROCEDURES: For each
      horse, anesthesia was induced by administration of xylazine, diazepam, and
      ketamine and maintained with sevoflurane for approximately 90 minutes (of which
      the last 60 minutes were under steady-state conditions) 3 times at 1-week
      intervals. For 1 anesthetic episode, each horse was allowed to recover from
      sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or
      xylazine and propofol were infused for 30 or 15 minutes, respectively, after
      termination of sevoflurane administration. Selected cardiopulmonary variables
      were measured during anesthesia and recovery. Recovery events were monitored and
      subjectively scored. RESULTS: Cardiopulmonary variables differed minimally among
      treatments, although the xylazine-propofol infusion was associated with greater
      respiratory depression than was the xylazine-ketamine infusion. Interval from
      discontinuation of sevoflurane or infusion administration to standing did not
      differ significantly among treatments, but the number of attempts required to
      stand successfully was significantly lower after xylazine-propofol infusion,
      compared with the number of attempts after sevoflurane alone. Scores for recovery
      from anesthesia were significantly lower (ie, better recovery) after either
      infusion, compared with scores for sevoflurane administration alone. CONCLUSIONS
      AND CLINICAL RELEVANCE: Xylazine-ketamine or xylazine-propofol infusion
      significantly improved quality of recovery from sevoflurane anesthesia in horses.
      Xylazine-ketamine or xylazine-propofol infusions may be of benefit during
      recovery from sevoflurane anesthesia in horses for which a smooth recovery is
      particularly critical. However, oxygenation and ventilation should be monitored
      carefully.

PMID- 22369526
TI  - Evaluation of a fracture pain model in domestic pigeons (Columba livia).
AB  - OBJECTIVE: To validate a model of postfracture pain in perching birds. ANIMALS:
      21 adult domestic pigeons (Columba livia). PROCEDURES: In each bird, a
      standardized osteotomy of 1 femur was performed and the fracture was immobilized
      with an intramedullary pin. Degree of postoperative pain was evaluated 6 times/d
      for 4 days by use of 3 methods: an electronic perch for assessment of weight
      bearing load differential of the pelvic limbs, 4 numeric rating pain scales for
      assessment of pain (all of which involved the observer in the same room as the
      bird), and analysis of video-recorded (observer absent) partial ethograms for
      bird activity and posture. Measurements obtained were compared with data
      collected before the surgery to evaluate the ability of these methods to detect
      pain. RESULTS: The weight-bearing load differential was a sensitive, specific,
      reliable, and indirect measure of fracture-associated pain in the model used. Two
      of 4 tested pain scales (fractured limb position and subjective evaluation of
      degree of pain) were sensitive and specific for detecting pain and were reliable
      in a research setting. Interobserver reliability of the 4 pain scales was
      excellent. Partial ethograms were sensitive for identifying pain-associated
      behavior in pigeons, particularly during the first 2 days after surgery.
      CONCLUSIONS AND CLINICAL RELEVANCE: The fracture pain model was reliable and
      reproducible and may be useful for experimental studies involving postsurgical
      pain in pigeons. Weight-bearing load differential was the most sensitive and
      specific means of determining degree of pain in pigeons during the first 4 days
      after hind limb fracture induction.

PMID- 22369527
TI  - Analgesic effects of meloxicam administration on postoperative orthopedic pain in
      domestic pigeons (Columba livia).
AB  - OBJECTIVE: To assess the analgesic effects of 2 doses of meloxicam on the degree
      of postoperative orthopedic pain in pigeons. ANIMALS: 21 domestic pigeons
      (Columba livia). PROCEDURES: In each bird, a standardized osteotomy of 1 femur
      was performed and the fracture was immobilized with an intramedullary pin. Birds
      were randomly allocated to receive saline (0.9% NaCl) solution (control) or
      meloxicam (0.5 mg/kg [low dose] or 2.0 mg/kg [high dose]). The first treatment
      was administered i.m. after surgery was completed. Subsequent treatments were
      administered p.o. every 12 hours for 9 days. Degree of postoperative pain was
      assessed for the first 4 days after surgery by use of 3 methods: an electronic
      perch for assessment of weight-bearing load differential of the pelvic limbs, 4
      pain scales, and analysis of video-recorded partial ethograms for bird activity
      and posture. RESULTS: No significant differences were observed between the
      control group and the low-dose meloxicam group in any tested variable. The high
      dose meloxicam group had a greater degree of weight bearing on the affected limb
      from the second to the fourth postoperative day as well as lower pain scores for
      at least the first 2 postoperative days, compared with the other groups. Return
      to presurgical behavior was achieved faster in pigeons that received high-dose
      meloxicam than in the other groups. No adverse effects were observed. CONCLUSIONS
      AND CLINICAL RELEVANCE: Administration of meloxicam at 0.5 mg/kg appeared
      ineffective in minimizing postoperative orthopedic pain in pigeons, but the 2.0
      mg/kg dose provided quantifiable analgesia that appeared safe in this species in
      experimental conditions.

PMID- 22369528
TI  - Comparison of an inertial sensor system with a stationary force plate for
      evaluation of horses with bilateral forelimb lameness.
AB  - OBJECTIVE: To assess the analytic sensitivity of an inertial sensor system for
      detection of the more severely affected forelimb in horses with bilateral
      lameness. ANIMALS: 18 adult horses with forelimb lameness. PROCEDURES: Horses
      were fitted with inertial sensors and evaluated for lameness with a stationary
      force plate as they were trotted in a straight line. Inertial sensor-derived
      measurements for vertical head movement asymmetry (HMA) and vector sum (VS) of
      maximum and minimum head height differences between right and left halves of the
      stride were used to predict differences in mean peak vertical force (PVF) as a
      percentage of body weight between the right and left forelimbs. Repeatability was
      compared by calculation of the intraclass correlation coefficient (ICC) for each
      variable. Correct classification percentages for the lamer forelimb were
      determined by use of a stationary force plate as the standard. RESULTS: SEs of
      the prediction of difference in PVF between the right and left forelimbs from HMA
      and VS were 6.1% and 5.2%, respectively. Head movement asymmetry (ICC, 0.72) was
      less repeatable than PVF (ICC, 0.86) and VS (ICC, 0.84). Associations were
      positive and significant between HMA (R(2) = 0.73) and VS (R(2) = 0.81) and the
      difference in PVF between the right and left forelimbs. Correct classification
      percentages for HMA and VS for detecting the lamer forelimb were 83.3% and 77.8%,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that an
      inertial sensor system to measure vertical asymmetry (HMA and VS) due to forelimb
      lameness in horses trotting in a straight line has adequate analytic sensitivity
      for clinical use. Additional studies are required to assess specificity of the
      system.

PMID- 22369529
TI  - Fractures in regions of adaptive modeling and remodeling of central tarsal bones
      in racing Greyhounds.
AB  - OBJECTIVE: To evaluate and compare bone modeling and remodeling in fractured and
      non-fractured central tarsal bones (CTBs) of racing Greyhounds. SAMPLE: Paired
      cadaveric tarsi from 6 euthanized racing Greyhounds with right CTB fractures and
      6 racing Greyhounds with other nontarsal injuries. PROCEDURES: CTBs were
      dissected and fractured CTBs were reconstructed. Central tarsal bones were
      evaluated through standard and nonscreen high-detail radiography, computed
      tomography, and histologic examination. The bone mineral density (BMD) was
      calculated adjacent to fracture planes and as a gradient on sagittal computed
      tomographic images. Sagittal and transverse plane sections of bone were obtained
      and submitted for subjective histologic assessment. Linear mixed-effects models
      were used to compare findings. RESULTS: Fractured right CTBs had greater BMD in
      the dorsal and midbody regions of the sagittal plane sections than did
      nonfractured CTBs. The BMD ratios from bone adjacent to the dorsal slab fracture
      planes were not different between fractured and nonfractured right CTBs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Findings supported the existence of site
      specific bone adaptation in CTBs of Greyhounds, with modeling and remodeling
      patterns that were unique to fractured right CTBs. The dorsal and midbody regions
      of fractured bones had greater BMD, and fractures occurred through these zones of
      increased BMD.

PMID- 22369530
TI  - Accuracy and precision of computer-assisted analysis of bone density via
      conventional and digital radiography in relation to dual-energy x-ray
      absorptiometry.
AB  - OBJECTIVE: To evaluate the precision and accuracy of assessing bone mineral
      density (BMD) by use of mean gray value (MGV) on digitalized and digital images
      of conventional and digital radiographs, respectively, of ex vivo bovine and
      equine bone specimens in relation to the gold-standard technique of dual-energy x
      ray absorptiometry (DEXA). SAMPLE: Left and right metatarsal bones from 11 beef
      cattle and right femurs from 2 horses. PROCEDURES: Bovine specimens were imaged
      by use of conventional radiography, whereas equine specimens were imaged by use
      of computed radiography (digital radiography). Each specimen was subsequently
      scanned by use of the same DEXA equipment. The BMD values resulting from each
      DEXA scan were paired with the MGVs obtained by use of software on the
      corresponding digitalized or digital radiographic image. RESULTS: The MGV
      analysis of digitalized and digital x-ray images was a precise (coefficient of
      variation, 0.1 and 0.09, respectively) and highly accurate method for assessing
      BMD, compared with DEXA (correlation coefficient, 0.910 and 0.937 for
      conventional and digital radiography, respectively). CONCLUSIONS AND CLINICAL
      RELEVANCE: The high correlation between MGV and BMD indicated that MGV analysis
      may be a reliable alternative to DEXA in assessing radiographic bone density.
      This may provide a new, inexpensive, and readily available estimate of BMD.

PMID- 22369531
TI  - Quantitative perfusion analysis of the pancreas and duodenum in healthy dogs by
      use of contrast-enhanced ultrasonography.
AB  - OBJECTIVE: To investigate contrast-enhanced ultrasonography as a minimally
      invasive method for the subjective and quantitative assessment of pancreatic and
      duodenal perfusion in healthy adult dogs, with reference to perfusion in adjacent
      liver tissue. ANIMALS: 8 clinically normal adult dogs. PROCEDURES: Contrast
      enhanced ultrasonograms of the right pancreatic limb, proximal portion of the
      descending duodenum, and adjacent liver were acquired after i.v. administration
      of a microbubble contrast medium. Following subjective evaluation, quantitative
      time-intensity curves were generated from regions of interest in the pancreas,
      duodenum, and liver. Five contrast medium characteristics representing perfusion
      parameters were determined for each organ and used for statistical analysis:
      interval to arrival, inflow rate, peak intensity (PI), time of peak intensity
      (TPI), and outflow rate. RESULTS: Significant associations between pancreatic and
      duodenal values were found for interval to contrast medium arrival, PI, TPI, and
      outflow rate. Pancreatic and duodenal inflow rates were not correlated. Inflow
      and outflow rates were significantly faster and TPI significantly shorter for the
      pancreas and duodenum, compared with values for the liver. There was no
      significant difference among all 3 organs for interval to arrival and PI of
      contrast medium. Subjective evaluation findings corresponded to quantitative
      analysis results. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
      contrast-enhanced ultrasonography may be a useful, minimally invasive method for
      evaluating pancreatic and duodenal perfusion in dogs. The data from healthy dogs
      reported here could aid in the assessment of pancreatic and duodenal conditions
      and their response to medical treatment.

PMID- 22369532
TI  - Comparison of multi-detector row computed tomography with echocardiography for
      assessment of left ventricular function in healthy dogs.
AB  - OBJECTIVE: To evaluate the use of retrospectively ECG-gated, contrast-enhanced,
      multi-detector row computed tomography (MDCT) for assessment of left ventricular
      function in dogs and to compare the results with those obtained by use of 2-D and
      M-mode echocardiographc techniques. ANIMALS: 10 healthy Beagles. PROCEDURES: Dogs
      underwent MDCT (performed by use of a 64-detector row CT system) and
      echocardiography under general anesthesia. Left ventricular end-systolic volume
      (ESV), end-diastolic volume (EDV), and ejection fraction (EF) were determined in
      MDCT-generated multiplanar reformatted images by use of Simpson and biplane area
      length calculation methods. Results were compared with left ventricular ESV, EDV,
      and EF determined in echocardiographc images by use of Teichholz and bullet
      method calculations. Results were evaluated via Deming regression analysis and
      Pearson correlation tests. Bland-Altman analysis was used to assess limits of
      agreement and systematic errors between the 2 methods. RESULTS: Mean values for
      EDV and ESV determined by use of MDCT were highly correlated with those
      determined by use of echocardiography, regardless of the calculation methods
      compared (r = 0.91 to 0.96); volumes determined by use of MDCT appeared to be
      higher than those determined by use of echocardiography, although most
      differences were nonsignificant. Mean EF determined by use of MDCT with the
      Simpson calculation method was highly correlated with that determined by use of
      echocardiography with bullet method calculations (r = 0.90). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that assessment of left ventricular volume
      and function in dogs is feasible with MDCT. To estimate left ventricular EF with
      MDCT. use of the Simpson calculation method is advised.

PMID- 22369533
TI  - Prevalence of perinuclear antineutrophilic cytoplasmic autoantibodies in serum of
      healthy Soft Coated Wheaten Terriers in the United Kingdom.
AB  - OBJECTIVE: To estimate the prevalence of perinuclear antineutrophilic cytoplasmic
      autoantibodies (pANCA) in the serum of healthy Soft Coated Wheaten Terriers
      (SCWTs) in the United Kingdom and to identify potential risk factors and
      heritability patterns associated with a positive result for pANCA. ANIMALS: 188
      SCWTs (age range, 18 months to 14.3 years). PROCEDURES: Blood samples were
      obtained from SCWTs in various locations in England. Serum was tested for pANCA
      by use of an immunofluorescence assay, and total protein and albumin
      concentrations were determined. Pedigrees were evaluated to identify close
      relatives that had protein-losing enteropathy (PLE) or protein-losing nephropathy
      (PLN). RESULTS: 39 of 188 (20.7%) dogs, including young dogs, had positive
      results for pANCA. Dogs had significantly higher odds of having positive results
      for pANCA if they had at least 1 littermate that had PLE or PLN (odds ratio,
      12.1) or if they had at least 1 full sibling from another litter known to be
      affected with PLE or PLN (odds ratio, 4.0). CONCLUSIONS AND CLINICAL RELEVANCE;
      This study revealed a high prevalence of pANCA in the serum of a representative
      sample of healthy SCWTs in the United Kingdom and a significant association
      between positive results for pANCA and a diagnosis of PLE or PLN in a sibling.

PMID- 22369535
TI  - Prevalence of antimicrobial resistance in relation to virulence genes and
      phylogenetic origins among urogenital Escherichia coli isolates from dogs and
      cats in Japan.
AB  - OBJECTIVE: To assess the status of antimicrobial resistance (AMR), identify
      extraintestinal virulence factors (VFs) and phylogenetic origins, and analyze
      relationships among these traits in extraintestinal pathogenic Escherichia coli
      (ExPEC) isolates from companion animals. SAMPLE: 104 E coli isolates obtained
      from urine or genital swab samples collected between 2003 and 2010 from 85 dogs
      and 19 cats with urogenital infections in Japan. PROCEDURES: Antimicrobial
      susceptibility of isolates was determined by use of the agar dilution method; a
      multiplex PCR assay was used for VF gene detection and phylogenetic group
      assessment. Genetic diversity was evaluated via randomly amplified polymorphic
      DNA analysis. RESULTS: Of the 104 isolates, 45 (43.3%) were resistant to > 2
      antimicrobials. Phylogenetically, 64 (61.5%), 22 (21.2%), 13 (12.5%), and 5
      (4.8%) isolates belonged to groups B2, D, B1, and A, respectively. Compared with
      other groups, group B2 isolates were less resistant to all tested antimicrobials
      and carried the pap, hly, and cnf genes with higher frequency and the aer gene
      with lower frequency. The aer gene was directly associated and the pap, sfa, hly,
      and cnf genes were inversely associated with AMR. Randomly amplified polymorphic
      DNA analysis revealed 3 major clusters, comprised mainly of group B1, B2, and D
      isolates; 2 subclusters of group B2 isolates had different VF and AMR status.
      CONCLUSIONS AND CLINICAL RELEVANCE; Prevalences of multidrug resistance and human
      like phylogenetic origins among ExPEC isolates from companion animals in Japan
      were high. It is suggested that VFs, phylogenetic origins, and genetic diversity
      are significantly associated with AMR in ExPEC.

PMID- 22369536
TI  - Influence of exercise on the distribution of technetium Tc 99m medronate
      following intra-articular injection in horses.
AB  - OBJECTIVE: To determine the effects of exercise on the distribution and
      pharmacokinetics of technetium Tc 99m medronate ((99m)Tc-MDP) following intra
      articular (IA) injection in horses. ANIMALS: 5 horses. PROCEDURES: 1
      antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5),
      and the contralateral ACJ was evaluated in the nonexercised group (5) after a
      minimum washout period of 7 days. Following IA injection of (99m)Tc-MDP (148
      MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15,
      20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma
      and scintigraphic radioactivity were determined over time, and pharmacokinetic
      parameters were generated via noncompartmental and compartmental analyses. Each
      horse was monitored via physical and lameness examination and ACJ synovial fluid
      analysis before injection and at days 1, 2, 3, and 7. RESULTS: Lameness was not
      observed. Mean +/- SD synovial fluid WBC count increased at day 1 (exercised, 721
      +/- 234 cells/MUL; nonexercised, 948 +/- 223 cells/MUL), but returned to baseline
      at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the
      exercised group (16.00 +/- 2.35 minutes) than the nonexercised group (43.75 +/-
      3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves
      revealed a greater negative slope in the exercised group within the first 25
      minutes. There was no difference in absorption or elimination rate constants in a
      2-compartment model. CONCLUSIONS AND CLINICAL RELEVANCE: IA injection of (99m)Tc
      MDP was safe and effective for evaluating synovial solute distribution. Exercise
      significantly increased early transfer of (99m)Tc-MDP from the ACJ into plasma,
      although absorption and elimination rate constants were not affected. Exercise
      may affect synovial clearance and withdrawal times of medications administered
      IA.

PMID- 22369537
TI  - Assessment of reactive oxygen species production in cultured equine skeletal
      myoblasts in response to conditions of anoxia followed by reoxygenation with or
      without exposure to peroxidases.
AB  - OBJECTIVE: To culture equine myoblasts from muscle microbiopsy specimens, examine
      myoblast production of reactive oxygen species (ROS) in conditions of anoxia
      followed by reoxygenation, and assess the effects of horseradish peroxidase (HRP)
      and myeloperoxidase (MPO) on ROS production. ANIMALS: 5 healthy horses (5 to 15
      years old). PROCEDURES: Equine skeletal myoblast cultures were derived from 1 or
      2 microbiopsy specimens obtained from a triceps brachii muscle of each horse.
      Cultured myoblasts were exposed to conditions of anoxia followed by reoxygenation
      or to conditions of normoxia (control cells). Cell production of ROS in the
      presence or absence of HRP or MPO was assessed by use of a gas chromatography
      method, after which cells were treated with a 3,3'-diaminobenzidine chromogen
      solution to detect peroxidase binding. RESULTS: Equine skeletal myoblasts were
      successfully cultured from microbiopsy specimens. In response to anoxia and
      reoxygenation, ROS production of myoblasts increased by 71%, compared with that
      of control cells. When experiments were performed in the presence of HRP or MPO,
      ROS production in myoblasts exposed to anoxia and reoxygenation was increased by
      228% and 183%, respectively, compared with findings for control cells. Chromogen
      reaction revealed a close adherence of peroxidases to cells, even after several
      washes. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that equine
      skeletal myoblast cultures can be generated from muscle microbiopsy specimens.
      Anoxia-reoxygenation-treated myoblasts produced ROS, and production was enhanced
      in the presence of peroxidases. This experimental model could be used to study
      the damaging effect of exercise on muscles in athletic horses.

PMID- 22369538
TI  - Effect of environmental conditions on degree of hoof wall hydration in horses.
AB  - OBJECTIVE: To determine the effect of various environmental conditions on the
      degree of hydration in hoof wall horn tissue from feral horses and investigate
      the effect of short-term foot soaking on moisture content in hoof wall and sole
      tissue in domestic horses. ANIMALS: 40 feral horses from 3 environments (wet and
      boggy [n = 10], partially flooded [20], and constantly dry desert [10]) and 6
      nonferal Quarter Horses. PROCEDURES: The percentage of moisture content of hoof
      wall samples from feral horses was measured in vitro. In a separate evaluation,
      the percentage of moisture content of hoof wall and sole tissue was measured in
      the dry and soaked forefeet of Quarter Horses. RESULTS: Mean +/- SD percentage of
      moisture content was 29.6 +/- 5.1%, 29.5 +/- 5.8%, and 29.5 +/- 2.9% for feral
      horses from the wet and boggy, partially flooded, and constantly dry desert
      environments, respectively. Moisture content did not differ among the 3 groups,
      nor did it differ between dry and soaked hoof wall samples from nonferal horses.
      However, soaking in water for 2 hours resulted in a significant increase in the
      percentage of moisture content of the sole. CONCLUSIONS AND CLINICAL RELEVANCE:
      Environmental conditions do not appear to affect moisture content in the hoof
      wall horn. Soaking horses' feet regularly in water would be unlikely to change
      the degree of hydration in the hoof wall horn but may further hydrate the sole.

PMID- 22369539
TI  - Isometric responses of isolated intrapulmonary bronchioles from cats with and
      without adult heartworm infection.
AB  - OBJECTIVE: To determine the isometric responses of isolated intrapulmonary
      bronchioles from cats with and without adult heartworm infection. ANIMALS: 13
      purpose-bred adult cats. PROCEDURES: Cats were infected with 100 third-stage
      larvae or received a sham inoculation, and the left caudal lung lobe was
      collected 278 to 299 days after infection. Isometric responses of intrapulmonary
      bronchiolar rings were studied by use of a wire myograph. Three cycles of
      contractions induced by administration of 10 MUM acetylcholine were followed by
      administration of the contractile agonists acetylcholine, histamine, and 5
      hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were
      constricted by administration of 10 MUM 5-hydroxytryptamine, and concentration
      response curves were generated from administration of sodium nitroprusside,
      isoproterenol, and substance P. RESULTS: Compared with tissues from control cats,
      contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in
      tissues from heartworm-infected cats. Relaxation to isoproterenol was
      significantly reduced in tissues from heartworm-infected cats. Relaxation to
      substance P was increased in tissues from heartworm-infected cats, but relaxation
      to sodium nitroprusside was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggested that despite increased bronchiolar wall thickness in heartworm
      infected cats, a hyperreactive response of the bronchiolar smooth muscle is not
      the primary mechanism of respiratory tract clinical signs. Reduced response of
      the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation
      in heartworm-infected cats.

PMID- 22369541
TI  - Evidence, the basis for practice ... and politics!

PMID- 22369540
TI  - Effects of a urolith prevention diet on urine compositions of glycosaminoglycans,
      Tamm-Horsfall glycoprotein, and nephrocalcin in cats with calcium oxalate
      urolithiasis.
AB  - OBJECTIVE: To evaluate urine concentrations of glycosaminoglycans, Tamm-Horsfall
      glycoprotein, and nephrocalcin in cats fed a diet formulated to prevent calcium
      oxalate uroliths. ANIMALS: 10 cats with calcium oxalate urolithiasis. PROCEDURES:
      In a previous study conducted in accordance with a balanced crossover design,
      cats were sequentially fed 2 diets (the diet each cat was consuming prior to
      urolith detection and a diet formulated to prevent calcium oxalate uroliths).
      Each diet was fed for 8 weeks. At the end of each 8-week period, a 72-hour urine
      sample was collected. Concentrations of glycosaminoglycans, Tamm-Horsfall
      glycoprotein, and the 4 isoforms of nephrocalcin in urine samples collected
      during that previous study were measured in the study reported here. RESULTS;
      Diet had no effect on the quantity of Tamm-Horsfall glycoprotein and nephrocalcin
      in urine. However, the urine concentration of glycosaminoglycans was
      significantly higher during consumption of the urolith prevention diet.
      CONCLUSIONS AND CLINICAL RELEVANCE: Feeding a urolith prevention diet increased
      the urine concentration of glycosaminoglycans, which are glycoprotein inhibitors
      of growth and aggregation of calcium oxalate crystals.

PMID- 22369543
TI  - Qualitative outcome assessment and research on chronic disease management in
      general practice. Highlights from a keynote lecture, EGPRN May 2011, Nice.
AB  - At its 2011 conference in Nice, France, the European General Practice Research
      Network (EGPRN), considered the issue of Relevant Outcome Measures in General
      Practice Research into Chronic Diseases. This paper, which is adapted from a
      keynote lecture given during that conference, considers the role of qualitative
      outcome assessments in research. Such assessments have a great deal in common
      with the patient-centred approach of general practice as they can capture the
      overall state of a patient rather than capturing only certain aspects. Research
      suggests that patients can be categorized, based on qualitative outcome
      assessment, and over time might change category. This approach to assessment
      brings to our attention alternative ways of considering the future: future as
      currently being made or future as predictable, at least to some extent. Although
      general practice needs the evidence from research that predicts the future, it
      also needs to engage in research that seeks to understand patients as they make
      their future, and to understand the impact of clinical interventions on this
      process.

PMID- 22369549
TI  - Barcoding Queensland Fruit Flies (Bactrocera tryoni): impediments and
      improvements.
AB  - Identification of adult fruit flies primarily involves microscopic examination of
      diagnostic morphological characters, while immature stages, such as larvae, can
      be more problematic. One of the Australia's most serious horticultural pests, the
      Queensland Fruit Fly (Bactrocera tryoni: Tephritidae), is of particular
      biosecurity/quarantine concern as the immature life stages occur within food
      produce and can be difficult to identify using morphological characteristics. DNA
      barcoding of the mitochondrial Cytochrome Oxidase I (COI) gene could be employed
      to increase the accuracy of fruit fly species identifications. In our study, we
      tested the utility of standard DNA barcoding techniques and found them to be
      problematic for Queensland Fruit Flies, which (i) possess a nuclear copy (a numt
      pseudogene) of the barcoding region of COI that can be co-amplified; and (ii) as
      in previous COI phylogenetic analyses closely related B. tryoni complex species
      appear polyphyletic. We found that the presence of a large deletion in the numt
      copy of COI allowed an alternative primer to be designed to only amplify the
      mitochondrial COI locus in tephritid fruit flies. Comparisons of alternative
      commonly utilized mitochondrial genes, Cytochrome Oxidase II and Cytochrome b,
      revealed a similar level of variation to COI; however, COI is the most
      informative for DNA barcoding, given the large number of sequences from other
      tephritid fruit fly species available for comparison. Adopting DNA barcoding for
      the identification of problematic fly specimens provides a powerful tool to
      distinguish serious quarantine fruit fly pests (Tephritidae) from endemic fly
      species of lesser concern.

PMID- 22369551
TI  - Clinical considerations for increasing occlusal vertical dimension: a review.
AB  - The purpose of this article is to discuss the clinical considerations related to
      increasing the occlusal vertical dimension (OVD) when restoring a patient's
      dentition. Thorough extraoral and intraoral evaluations are mandatory to assess
      the suitability of increasing OVD. In the literature, multiple techniques have
      been proposed to quantify OVD loss. However, the techniques lack consistency and
      reliability, which in turn affects the decision of whether to increase the OVD.
      Therefore, increasing OVD should be determined on the basis of the dental
      restorative needs and aesthetic demands. In general, a minimal increase in OVD
      should be applied, though a 5 mm maximum increase in OVD can be justified to
      provide adequate occlusal space for the restorative material and to improve
      anterior teeth aesthetics. The literature reflects the safety of increasing the
      OVD permanently, and although signs and symptoms may develop, these are usually
      of an interim nature. Whenever indicated, the increase in OVD should be achieved
      with fixed restorations rather than a removable appliance, due to the predictable
      patient adaptation. The exception to this is for patients with TMD, where
      increasing the OVD should still be achieved using removable appliances to control
      TMD-associated symptoms before considering any form of irreversible procedure.

PMID- 22369552
TI  - Modulation of epithelial tight junctions by TGF-beta 3 in cultured oral
      epithelial cells.
AB  - BACKGROUND: Previous studies have indicated that transforming growth factor beta
      3 (TGF-beta3) was strongly expressed both in the gingival epithelium and the
      poorly structured pocket epithelium. METHODS: A comprehensive analysis of the
      profile of tight junction proteins was carried out by quantitative real-time RT
      PCR, Western blot and paracellular permeability assays. RESULTS: Active TGF-beta3
      protein added to monolayers of cultured oral epithelial cells initially reduced
      the permeability to dextran (10 kDa), followed by an increase in permeability.
      Three hours after the addition of TGF-beta3, expression of genes encoding tight
      junction components was selectively up- or down-regulated. In addition, up- or
      down-regulation of expression of several tight junction associated proteins was
      observed, although the protein changes did not parallel changes in gene
      expression. To confirm that TGF-beta3 plays a role in epithelial barrier
      function, a selective Src family kinase inhibitor saracatinib (AZD0530) was added
      to cells treated with active TGF-beta3. Tight junction proteins claudins-2, -20
      and ZO-2 were significantly decreased, but claudin-4 and -18 were significantly
      increased. CONCLUSIONS: These results suggest that TGF-beta3 is involved in the
      modulation of epithelial barrier function by regulating assembly of tight
      junctions.

PMID- 22369553
TI  - Dentists' perceptions of a new local anaesthetic drug--articaine.
AB  - BACKGROUND: Articaine is a new local anaesthetic drug introduced to the
      Australian dental market. The aim of this study was to elicit information
      regarding the use of articaine in Australia, and factors that influence attitudes
      towards adoption of new technology. METHODS: A self-administered postal
      questionnaire was sent to a stratified systematic sample of dentists who were
      members of the Australian Dental Association, with questions regarding details
      about articaine use and how influences such as education and scientific
      literature affect their adoption of new technology. RESULTS: Of the sample, 53%
      responded and over 70% of dentists surveyed used articaine, with 95% and 97% of
      respondents identifying scientific literature and continuing professional
      development courses respectively as influencing factors in their adoption of new
      technology. The most common reason for not using articaine was no perceived
      advantage and the most influential factor that would encourage non-users to start
      using articaine was a scientifically proven advantage. Senior clinicians,
      specialists and public sector dentists were less likely to use articaine.
      CONCLUSIONS: A majority of Australian dentists were using articaine and cited
      continuing professional development courses, scientific literature and anecdotal
      peer reports as being influential in their adoption of new technology.

PMID- 22369554
TI  - The all-ceramic, inlay supported fixed partial denture. Part 3. Experimental
      approach for validating the finite element analysis.
AB  - In a previous study, the authors used a finite element analysis (FEA) to evaluate
      the stresses developed during the loading of an all-ceramic, inlay supported
      fixed partial denture and compared it with the more traditional full crown
      supported prosthesis. To date there has been little research into correlating the
      responses of the numerical model against physical mechanical tests; such
      validation analysis is crucial if the results from the FEA are to be confidently
      relied upon. This study reports on the experimental methods used to compare with
      the FEA and thereby to validate the predictive fracture behaviour of the
      numerical model. This study also outlines the methods for manufacture and testing
      of the ceramic structure along with observations of the fracture tests. In
      addition the procedure used for developing the FEA model for the test system is
      outlined.

PMID- 22369555
TI  - Non-surgical periodontal therapy affects metabolic control in diabetics: a
      randomized controlled clinical trial.
AB  - BACKGROUND: Periodontal diseases and diabetes are two common diseases with high
      prevalence. Many clinicians have accepted the relationship between these two
      diseases. Some investigators have reported that periodontal treatment may enhance
      the metabolic control of diabetes. The effects of non-surgical periodontal
      treatment on metabolic control in people with type 2 diabetes mellitus (DM2) were
      examined. METHODS: Forty patients with DM2 and chronic periodontitis [mean age =
      50.29 years; mean glycated haemoglobin (HbA1c) = 8.72] were randomly assigned to
      two groups. The treatment group (n = 22) received full-mouth scaling and root
      planing, whereas the control group (n = 18) received no periodontal treatment.
      Gingival index (GI), plaque index (PI), probing pocket depth (PPD), clinical
      attachment level (CAL), fasting plasma glucose (FPG), HbA1c, total cholesterol
      (TC), triglyceride (TG) and cholesterol levels were recorded at baseline and
      compared to data collected three months later. RESULTS: The groups did not differ
      in gender ratio, age or clinical parameters [PPD (p = 0.107), CAL (p = 0.888), PI
      (p = 0.180)] and biochemical markers at baseline [FPG (p = 0.429), HbA1c (p =
      0.304), TG (p = 0.486), TC (p = 0.942), LDL (p = 0.856) and HDL (p = 0.881)].
      FPG, HbA1c and clinical parameters differed between the treatment and control
      groups (p = 0.006, 0.003 and 0, respectively). From baseline to follow-up (after
      three months), HbA1c levels decreased in the treated group (p = 0.003). In the
      same time period, FPG, GI, PPD and CAL increased in the control group (p = 0.016,
      0.0, 0.0 and 0.004, respectively) but HbA1c did not change significantly.
      CONCLUSIONS: Non-surgical periodontal therapy could improve metabolic control in
      diabetic patients.

PMID- 22369556
TI  - Oral health inequalities in a national sample of Australian children aged 2-3 and
      6-7 years.
AB  - BACKGROUND: While inequalities in oral health are generally well documented, it
      is less clear whether such patterns are evident from early childhood. Using four
      measures of potential inequality, this study examined patterns in oral health for
      Australian children at ages 2-3 and 6-7 years. METHODS: Cross-sectional data from
      two cohorts of children in the Longitudinal Study of Australian Children (LSAC)
      were used to explore associations between reported oral health and four
      indicators of social disadvantage: socio-economic position (SEP), residential
      remoteness, Indigenous status and non-English speaking background. RESULTS: For
      both cohorts, lower SEP and Indigenous status were associated with higher odds of
      poor oral health on all three indicators, and less accessible location was
      associated with increased odds for caries. Non-English speaking background was
      associated with increased odds for caries experience in 2-3 year olds and non-use
      of dental services in the older cohort. Inequalities were larger in the older
      cohort for socio-economic position and toothbrushing. CONCLUSIONS: Marked social
      disparities in oral health appear as early as 2 years of age and remain evident
      in school-age children. Interventions to reduce such disparities should start as
      early as possible.

PMID- 22369557
TI  - Association between long-term aspirin use and periodontal attachment level in
      humans: a cross-sectional investigation.
AB  - BACKGROUND: Pharmaceutical inhibition of host response pathways may be an
      adjunctive or alternative strategy for treating periodontal diseases. In addition
      to inhibition of prostaglandin synthesis, aspirin is known to modify the action
      of cyclo-oxygenase, changing its activity to a lipoxygenase and leading to
      formation of lipoxins which have a proresolving effect. This study evaluated the
      periodontal attachment level of subjects on long-term low dose aspirin therapy.
      METHODS: Oral hygiene index simplified, clinical attachment loss and bleeding
      index were recorded for 162 subjects who were on long-term (>6 months) low dose
      (75 mg and 150 mg) aspirin therapy (study group) and 146 subjects not taking the
      drug (control group). RESULTS: Mean clinical attachment loss was 2.38 +/- 0.49 mm
      in the control group and 2.01 +/- 0.69 mm in the study group. The difference was
      statistically significant at p < 0.001. Correlation analysis suggested that there
      was a negative correlation between clinical attachment loss and duration of
      aspirin intake but the clinical attachment loss was not significantly different
      in the two dosage groups. CONCLUSIONS: The results of this study suggest that low
      dose aspirin may reduce the risk of periodontal attachment loss. This hypothesis
      needs to be tested by larger sample sized prospective cohort studies.

PMID- 22369558
TI  - Comparison of periosteal pedicle graft and subepithelial connective tissue graft
      for the treatment of gingival recession defects.
AB  - BACKGROUND: The use of periosteum as a pedicle graft in the treatment of gingival
      recession defects is a recent advancement. The subepithelial connective tissue
      graft (SCTG) is considered the gold standard for the treatment of gingival
      recession defects. The present randomized controlled trial was done to compare
      periosteal pedicle graft (PPG) with SCTG for the treatment of gingival recession
      defects. METHODS: 10 males and 10 females between the ages of 16 and 40 years
      (mean age 25.2 years) with Miller's Class I and II recessions >=3 mm participated
      in this one-year clinical study. They were assigned randomly to test group (PPG)
      and control group (SCTG). Results were evaluated based on parameters measuring
      patient satisfaction and clinical outcomes associated with two treatment
      procedures. Significance was set at p < 0.05. RESULTS: At the end of the study,
      the defect coverage was 3.1 +/- 0.13 mm or 92.6% in the test group compared to
      the control group in which the defect coverage was 2.70 +/- 0.11 mm or 88.5%. The
      difference between the two groups was statistically significant (p < 0.0001). The
      average residual defect was comparable between the two groups, i.e. 0.3 +/- 0.67
      and 0.5 +/- 0.84 in the PPG and SCTG group respectively. The test group was rated
      higher in terms of overall patient satisfaction (p < 0.02) and comfort during and
      after the procedure (p < 0.001). CONCLUSIONS: PPG and SCTG have comparable
      clinical effectiveness, but PPG is superior to SCTG in terms of patient-centred
      outcomes, reflecting improved patient comfort and overall patient satisfaction.

PMID- 22369559
TI  - Inhibition of early biofilm formation by glass-ionomer incorporated with
      chlorhexidine in vivo: a pilot study.
AB  - BACKGROUND: This pilot study investigated the antibiofilm effects of glass
      ionomer cements (GICs) and resin-modified glass-ionomer cements (RMGICs)
      incorporated with chlorhexidine (CHX) in vivo. METHODS: Experimental GICs and
      RMGICs containing 2% CHX were obtained by mixing CHX with the powder of GICs
      (CHXGIC) and RMGICs (CHXRMGIC). Four groups of specimens were prepared in a
      standardized size. After polishing and sterilization, they were bonded to the
      buccal surface of the molars in the first and second quadrant of volunteers and
      left untouched for 4 hours and 24 hours, respectively. The bacterial vitality of
      plaque was then analysed by confocal laser scanning microscopy (CLSM). The
      bacterial morphology and biofilm accumulation were determined by scanning
      electron microscopy (SEM). The pH value of biofilm was assessed by Plaque
      Indicator Kits. RESULTS: CLSM analysis revealed that bacterial vitality of the
      biofilm on CHXGIC and CHXRMGIC was significantly lower than that on GIC and
      RMGIC. SEM analysis indicated that the morphology of bacteria on CHXGIC and
      CHXRMGIC was irregular. The pH value of biofilm on the experimental materials
      presented no statistically significant difference. CONCLUSIONS: Twenty-four hour
      bacterial vitality on GICs and RMGICs with CHX are lower in micro-organisms than
      on conventional GICs and RMGICs.

PMID- 22369560
TI  - Effect of silver and fluoride ions on enamel demineralization: a quantitative
      study using micro-computed tomography.
AB  - BACKGROUND: This study aimed to investigate the effect of silver and fluoride
      ions on demineralization of enamel. METHODS: The coronal parts of 40 extracted
      sound premolars were prepared into tooth blocks. An unvarnished occlusal surface
      window (OW) and a flat buccal/lingual surface window (FW) were created for each
      tooth by covering all other surfaces with an acid-resistant varnish. These blocks
      were randomly allocated into four groups of 10 blocks each and immersed in
      respective solutions for 5 minutes: Group 1--2.36 M silver fluoride; Group 2-
      2.36 M potassium fluoride; Group 3--2.36 M silver nitrate; and Group 4--deionized
      water. After 7-day immersion in a buffered demineralization solution at pH 4.4,
      micro-CT scans were taken. RESULTS: Mean lesion depth in the FW area for tooth
      blocks in AgF, KF, AgNO(3) and control groups were 0 MUm, 3.3 +/- 10.3 MUm, 156.3
      +/- 30.8 MUm, and 173.6 +/- 48.6 MUm, respectively (p < 0.001). The difference in
      mean lesion depth between the AgNO(3) and control groups was not statistically
      significant (p > 0.05). Similar OW and FW lesions were observed in tooth blocks
      in the AgNO(3) and control groups. CONCLUSIONS: Topical application of a 2.36 M
      fluoride solution can inhibit demineralization of enamel while topical
      application of silver ions has little effect.

PMID- 22369561
TI  - Dental and periodontal complications of lip and tongue piercing: prevalence and
      influencing factors.
AB  - BACKGROUND: The aim of this study was to compare the prevalence of lip and tongue
      piercing complications and explore the effect of ornament time wear period,
      habits, ornament morphology and periodontal biotype on the development of
      complications. METHODS: One hundred and ten subjects with 110 lip and 51 tongue
      piercings were assessed for abnormal toothwear and/or tooth chipping/cracking
      (dental defects), gingival recession, clinical attachment loss and probing depth
      of teeth adjacent to the pierced site. Piercing habits (biting, rolling,
      stroking, sucking) were recorded. RESULTS: Wear time and habits significantly
      affected the prevalence of dental defects and gingival recession. Pierced site
      significantly affected dental defects prevalence, with greater prevalence for
      tongue than lip piercing. Wear time significantly affected attachment loss and
      probing depth. Attachment loss and probing depth did not significantly differ
      between tongue and lip piercings. Gingival recession was significantly associated
      with ornament height closure and stem length of tongue ornaments. Periodontal
      biotype was not significantly associated with gingival recession, attachment loss
      and probing depth. CONCLUSIONS: Dental defects prevalence is greater for tongue
      than lip piercing. Gingival recession is similar for tongue and lip piercing.
      Longer wear time of tongue and lip piercing is associated with greater prevalence
      of dental defects and gingival recession, as well as greater attachment loss and
      probing depth of teeth adjacent to pierced sites. Ornament morphology affects
      gingival recession prevalence.

PMID- 22369562
TI  - Evaluation of microtensile bond strength of different fissure sealants to bovine
      enamel.
AB  - BACKGROUND: The aim of this study was to evaluate the microtensile bond strength
      (MUTBS) of a new fissure sealant and compare it with conventional sealants which
      are applied to enamel alone, and also with self-etch and etch-and-rinse
      adhesives. METHODS: Enamel specimens were prepared and randomly distributed into
      three groups according to fissure sealant (Aegis, Helioseal F, Helioseal Clear).
      Each group was then subdivided according to adhesive system (Clearfil S3, Single
      Bond, no adhesive). A universal testing machine was used to measure MUTBS, and
      data were analysed using one-way ANOVA and Tukey's tests. RESULTS: MUTBS values
      for all Aegis subgroups were significantly lower than for comparable Helioseal F
      and Helioseal Clear subgroups (p < 0.05). No differences were observed in MUTBS
      of Helioseal F and Helioseal Clear (p > 0.05). In the Helioseal Clear group,
      MUTBS values for Single Bond were significantly higher than for Clearfil S3 (p <
      0.05). However, no significant differences were found between the MUTBS values of
      the adhesive subgroups in the Aegis or Helioseal F groups (p > 0.05).
      CONCLUSIONS: Sealant MUTBS values may be affected by material content. The
      addition of an adhesive may improve MUTBS values of sealant to enamel.

PMID- 22369563
TI  - Geographic redistribution of practice location of graduate dentists: a six-year
      retrospective analysis (2004-2009).
AB  - BACKGROUND: The purpose of this study was to analyse the geographic distribution
      of practice locations of graduate dentists from the University of Western
      Australia (UWA) over a period of six years. METHODS: Using data from open access
      sources, all practice locations of the UWA's dental graduates from 2004 to 2009
      were located. All practice locations were measured at the postcode level and the
      distribution of graduates was analysed across variables such as SEIFA (a socio
      economic index of disadvantage) and ARIA (an index of accessibility and
      remoteness). RESULTS: Of the 228 UWA graduates, an almost equal proportion of
      males (49.1%) and females (50.9%) graduated over the six-year period. Of all the
      local graduates, 83% continued to practice in Western Australia, with 78% of the
      practice locations alone in ARIA 1 (highly accessible areas) and 22% of the
      graduates distributed among the remaining ARIA regions. Fifty-one per cent of
      graduates practised in the 30% most affluent suburbs and only 11.5% practised in
      the most socio-economically disadvantaged 30% suburbs. In SEIFA decile 10 (least
      disadvantaged areas), the highest numbers of practising dental graduates were
      also from the earliest graduates, with numbers steadily declining over the year
      of graduation from 2004 to 2009 (i.e. the most recent graduates). CONCLUSIONS: An
      apparent association exists between year of graduation and practice location,
      with more experienced dentists working in urban and higher socio-economic areas.

PMID- 22369564
TI  - Oral focal mucinosis in an adolescent: a case report.
AB  - Oral focal mucinosis (OFM) is an uncommon soft tissue lesion of unknown
      aetiology. Clinically, it is most commonly found on the gingiva and presents as a
      painless, sessile or pedunculated mass that is the same colour as surrounding
      mucosa. Histologically, it is characterized by focal myxoid degeneration of
      connective tissue. OFM occurs predominantly in adults during the fourth and fifth
      decade of life, although it has been reported infrequently in children and
      adolescents. Diagnosis relies on histological analysis and treatment involves
      complete surgical excision. Recurrence is unreported. This case report describes
      the clinical and histological presentation and subsequent management of OFM in an
      adolescent female patient.

PMID- 22369565
TI  - Use of a modified shell technique for three-dimensional bone grafting:
      description of a technique.
AB  - BACKGROUND: Defects of the alveolar crest often lead to three-dimensional bone
      loss after tooth extraction. Therefore, hard tissue grafting is required prior to
      implant placement. Different techniques have been described in the literature.
      METHODS: In this case report three-dimensional hard tissue grafting was performed
      with a modified shell technique and autogenous bone harvested from the mandibular
      ramus. The shells were trimmed to a thickness of 1 mm and placed to recontour the
      ideal shape of the alveolar ridge. The shells were then fixed with micro titanium
      screws, and the gap between the shells and the alveolar ridge was filled with
      autogenous bone chips. RESULTS: Wound healing was uneventful. Consolidation of
      the bone graft showed almost no resorption and the implant was placed into vital
      bone. CONCLUSIONS: The described shell technique for rebuilding three-dimensional
      alveolar defects showed promising results and could be an alternative treatment
      to other hard tissue grafting techniques.

PMID- 22369566
TI  - The multidisciplinary management of a fused maxillary central incisor with a
      talon cusp.
AB  - BACKGROUND: A fused maxillary incisor required complex multidisciplinary
      treatment to preserve health and restore aesthetics. This report presents a rare
      case of a dental fusion between the maxillary right central incisor and a
      supernumerary tooth of a 9-year-old male patient with the chief complaint of the
      presence of a large anterior tooth. METHODS: Radiographic investigation and
      computerized tomography indicated there was no connection between pulp chambers.
      After dividing the crown with a diamond bur, the supernumerary tooth was removed
      and the diastema between the maxillary central incisors was closed by orthodontic
      treatment. The tooth was then restored with composite resin. RESULTS: The
      maxillary right central incisor was still healthy after a follow-up examination
      period of 24 months. CONCLUSIONS: A multidisciplinary approach with the
      cooperation of different practitioners can contribute to the success of a
      treatment plan.

PMID- 22369569
TI  - Patterned monolayer self-assembly programmed by side chain shape: four-component
      gratings.
AB  - A molecular recognition strategy based on alkadiyne side chain shape is used to
      self-assemble a four-component, 1D-patterned monolayer at the solution-HOPG
      interface. The designed monolayer unit cell contains six molecules and spans 23
      nm * 1 nm. The unit cell's internal structure and packing are driven by
      complementary shapes and lengths of six different alkadiyne side chains. A
      solution of the four compounds on HOPG self-assembles monolayers (i) comprised,
      almost entirely, of the intended unit cell, (ii) exhibiting patterned domains
      spanning 10(4) nm(2), and (iii) which are sufficiently robust that patterned
      domains survive solvent rinsing and drying. The patterned monolayer affords 1D
      feature spacings ranging from 3.3 to 23 nm. The results demonstrate the
      remarkable selectivity afforded by molecular recognition based on alkadiyne side
      chain shape and the ability to program highly complex 1D-patterns in self
      assembled monolayers.

PMID- 22369568
TI  - Transcriptomic profiles of peripheral white blood cells in type II diabetes and
      racial differences in expression profiles.
AB  - BACKGROUND: Along with obesity, physical inactivity, and family history of
      metabolic disorders, African American ethnicity is a risk factor for type 2
      diabetes (T2D) in the United States. However, little is known about the
      differences in gene expression and transcriptomic profiles of blood in T2D
      between African Americans (AA) and Caucasians (CAU), and microarray analysis of
      peripheral white blood cells (WBCs) from these two ethnic groups will facilitate
      our understanding of the underlying molecular mechanism in T2D and identify
      genetic biomarkers responsible for the disparities. RESULTS: A whole human genome
      oligomicroarray of peripheral WBCs was performed on 144 samples obtained from 84
      patients with T2D (44 AA and 40 CAU) and 60 healthy controls (28 AA and 32 CAU).
      The results showed that 30 genes had significant difference in expression between
      patients and controls (a fold change of <-1.4 or >1.4 with a P value <0.05).
      These known genes were mainly clustered in three functional categories: immune
      responses, lipid metabolism, and organismal injury/abnormaly. Transcriptomic
      analysis also showed that 574 genes were differentially expressed in AA diseased
      versus AA control, compared to 200 genes in CAU subjects. Pathway study revealed
      that "Communication between innate and adaptive immune cells"/"Primary
      immunodeficiency signaling" are significantly down-regulated in AA patients and
      "Interferon signaling"/"Complement System" are significantly down-regulated in
      CAU patients. CONCLUSIONS: These newly identified genetic markers in WBCs provide
      valuable information about the pathophysiology of T2D and can be used for
      diagnosis and pharmaceutical drug design. Our results also found that AA and CAU
      patients with T2D express genes and pathways differently.

PMID- 22369570
TI  - Results of computer-assisted sensory evaluation in 41 patients with
      erythromelalgia.
AB  - BACKGROUND: Erythromelalgia is a rare disorder characterized by the clinical
      syndrome of burning pain, warmth and redness of the limbs. Neurological
      abnormalities (both large- and small-fibre neuropathy) are common. There have
      been few published reports on the sensory status of patients with
      erythromelalgia. AIM: To investigate the results of quantitative sensation
      testing in erythromelalgia using computer-assisted sensory evaluation, including
      vibratory detection threshold, cool detection threshold and heat-pain threshold
      (HPT). METHODS: Patients who underwent dermatological or neurological evaluation
      of suspected erythromelalgia at our institution and received a final diagnosis of
      erythromelalgia were identified from a master diagnosis index covering the period
      January 1994 to June 2008. A retrospective chart review was performed. Main
      outcome measures were sensory abnormalities (e.g. pain, burning sensation,
      tingling) in response to heat, cooling and vibration during computer-assisted
      sensory testing. RESULTS: In total, 41 patients with erythromelalgia were
      enrolled in the study and underwent computer-assisted sensory evaluation. Of
      these, 34 patients (82.9%) had abnormal results. The commonest abnormality was
      isolated HPT: 11 patients (26.8%) had heat hypoalgesia and 18 (43.9%) had heat
      hyperalgesia, whereas only 2 (4.9%) of the healthy control patients had
      hyperalgesia on testing. CONCLUSIONS: Multiple sensory modalities were found to
      be abnormal in patients with erythromelalgia, with the commonest clinical
      abnormality being isolated heat-pain abnormality. These findings lend support to
      the notion that neuropathy underlies the clinical diagnosis of erythromelalgia.
      Future studies will explore the nature of the relationship between these sensory
      abnormalities and the clinical features of erythromelalgia.

PMID- 22369571
TI  - Do we still need supertrees?
AB  - The up-dated species level phylogeny for the carnivores using a supertree
      approach provides new insights into the evolutionary origin and relationships of
      carnivores. While the gain in biological knowledge is substantial, the supertree
      approach is not undisputed. I discuss the principles of supertree methods and the
      competitor supermatrix approaches. I argue that both methods are important to
      infer phylogenetic relationships.See research article
      http://www.biomedcentral.com/1741-7007/10/12.

PMID- 22369574
TI  - Testing compensatory health beliefs in a UK population.
AB  - Compensatory health beliefs, beliefs that healthy behaviours can compensate or
      neutralise unhealthy behaviours, have been proposed as one way of understanding
      why people engage in health-risk behaviours (Knauper, B., Rabiau, M., Cohen, O.,
      & Patriciu, N. (2004). Compensatory health beliefs scale development and
      psychometric properties. Psychology and Health, 19, 607-624). However, measuring
      compensatory health beliefs has proved a challenge, with several recent studies
      being unable to replicate the psychometric properties of Knauper et al.'s (2004)
      scales. The aims of this study were to: (1) test the factor structure of the
      compensatory health beliefs scale in the UK, (2) examine the predictive validity
      of the scale by testing the relationships between compensatory health beliefs and
      health behaviours over a six-month time interval and (3) assess the 6-month test
      retest reliability of the scale. A total of 393 participants completed measures
      of compensatory health beliefs and health behaviours at two time points separated
      by six months. The findings were potentially problematic for research into
      compensatory health beliefs: the factor structure was not confirmed, there was
      little evidence of predictive validity, and test-retest reliability was poor.
      Further research is required to understand the operation of compensatory health
      beliefs and to develop the measurement of compensatory health beliefs.

PMID- 22369572
TI  - Variations of the ataxia telangiectasia mutated gene in patients with chronic
      lymphocytic leukemia lack substantial impact on progression-free survival and
      overall survival: a Cancer and Leukemia Group B study.
AB  - The impact of mutation of the ATM (ataxia telangiectasia mutated) gene in chronic
      lymphocytic leukemia (CLL) treatment outcome has not been examined. We studied
      ATM mutations in 73 patients treated with fludarabine and rituximab. ATM gene
      mutation analysis was performed using temperature gradient capillary
      electrophoresis. The impact of detected variants on overall survival (OS) and
      progression-free survival (PFS) was tested with proportional hazards models. None
      of the 73 patients demonstrated truncating ATM mutations; 17 (23%, 95% confidence
      interval 14-35%) had non-silent variants (ATM-NSVs), including 13 known ATM
      polymorphisms and four missense variants. ATM-NSVs were not significantly
      associated with any baseline characteristics including immunoglobulin heavy chain
      variable gene (IGVH) status. In multivariable models, no significant differences
      in complete response (p =0.70), PFS (p =0.59) or OS (p =0.13) were observed. Our
      data indicate that truncating ATM mutations are rare in patients with CLL.
      Furthermore, in this dataset, these non-silent variants had limited impact on PFS
      and OS.

PMID- 22369575
TI  - On the molecular structure of uranium dicarbide: T-shape versus linear isomers.
AB  - A theoretical study of the molecular structure of uranium dicarbide has been
      carried out employing DFT, coupled cluster, and multiconfigurational methods. A
      triangular species, corresponding to a (5)A(2) electronic state, has been found
      to be the most stable UC(2) species. A triplet linear CUC species, which has been
      observed in recent infrared spectroscopy experiments, lies much higher in energy.
      A topological analysis of the electronic density has also been carried out. The
      triangular species is shown to be in fact a T-shape structure with a U-C
      interaction which can be considered to be a closed-shell interaction.

PMID- 22369576
TI  - Factors associated with hospitalisations for ambulatory care-sensitive conditions
      among persons with an intellectual disability: a publicly insured population
      perspective.
AB  - BACKGROUND: Hospitalisations for ambulatory care-sensitive (ACS) conditions are
      used as an indicator of access to, and the quality of, primary care. The
      objective was to identify factors associated with hospitalisations for ACS
      conditions among adults with an intellectual disability (ID) in the context of a
      publicly insured healthcare system. METHODS: This study examined adults with an
      ID living in a Canadian province between 1999 and 2003 identified from
      administrative databases. Using 5 years of data for the study population,
      characteristics of persons hospitalised or not hospitalised for ACS conditions
      were compared. Using a conceptual model, independent variables were selected and
      an analysis performed to identify which were associated with hospitalisations for
      ACS conditions. The correlated nature of the observations was accounted for
      statistically. RESULTS: Living in a rural area [odds ratio (OR) 1.3; 95%
      confidence intervals (CI) = 1.0, 1.8], living in an area with a high proportion
      of First Nations people (OR 2.3; 95% CI = 1.3, 4.1), and experiencing higher
      levels of comorbidity (OR 25.2; 95% CI = 11.9, 53.0) were all associated with a
      higher likelihood of being hospitalised for an ACS condition. Residing in higher
      income areas had a protective effect (OR 0.56; 95% CI = 0.37, 0.85). None of the
      health service resource variables showed statistically significant associations.
      CONCLUSIONS: Persons with an ID experience inequity in hospitalisations for ACS
      conditions according to rurality, income and proportion who are First Nations in
      a geographic area. This suggests that addressing the socio-economic problems of
      poorer areas and specifically areas densely populated by First Nations people may
      have an impact on the number of hospitalisations for ACS conditions. Study
      strengths and limitations and areas for potential future research are discussed.

PMID- 22369577
TI  - Intestinal glucose absorption in calves as affected by different carbohydrate
      sources.
AB  - From numerous recent studies, it has been demonstrated that the development of
      the forestomach system in ruminants and thus microbial carbohydrate fermentation
      do not exclude the potential of the small intestines for enzymatic carbohydrate
      digestion and subsequent monosaccharide absorption. However, the role of
      regulatory nutritional factors is still under discussion. Therefore, we
      investigated the kinetic parameters of intestinal Na(+) -dependent glucose
      absorption and SGLT1 expression using isolated brush border membrane vesicles
      (BBMV) from the jejunum of 10-week-old calves kept on either hay, concentrate or
      corn silage-based diets in addition to milk replacer. While the maximal transport
      capacity was significantly higher for concentrate and corn silage-fed animals,
      SGLT1 protein expression was highest in BBMV isolated from hay-fed animals. This
      observation differs from the prevalent conception that induction of Na(+) 
      dependent glucose uptake via SGLT1 is based on an increased number of
      transporters at the brush border membrane.

PMID- 22369578
TI  - The sociology of medical screening: past, present and future.
AB  - Medical screening raises fundamental issues for sociological inquiry, but at
      present a well-developed sociology of medical screening is lacking. This special
      issue on the sociology of screening brings together an exciting collection of new
      work that tackles medical screening from a variety of theoretical and
      methodological approaches. In this opening paper, we begin by explaining what we
      mean by screening, and why we believe screening merits sociological attention.
      Secondly, we reflect on the sociology of screening to date and provide an
      introduction for those new to this area. We then provide an overview of the
      papers in this collection, highlighting links and contrasts between papers. We
      conclude by reflecting on sociology's potential contribution to wider debates
      about screening, and propose future research directions.

PMID- 22369579
TI  - Screening: mapping medicine's temporal spaces.
AB  - This paper examines the history of population screening through an analysis of
      contemporary medical journals. The term was first used in the modern sense in the
      inter-war years to describe the school health examination which sought to
      identify the early signs of disease and abnormality, a strategy which was
      extended to new recruits during the Second World War. After the war, screening
      began to target those illnesses in the civilian population which had a clear
      temporal trajectory, especially 'chronic' illnesses. Since the 1980s, enthusiasm
      for population screening has declined within the medical community: opportunistic
      screening has seemed more appropriate for diseases with multifactorial aetiology,
      and those programmes which have survived have been increasingly challenged
      through an expanding analysis of their potential harms. In identifying the early
      precursors of clinical disease in apparently normal populations, however,
      screening heralded the emergence of a new form of clinical practice concerned
      with the surveillance of 'healthy' patients within the context of new temporal
      spaces of illness.

PMID- 22369581
TI  - A method to identify important dynamical states in Boolean models of regulatory
      networks: application to regulation of stomata closure by ABA in A. thaliana.
AB  - BACKGROUND: We introduce a method to analyze the states of regulatory Boolean
      models that identifies important network states and their biological influence on
      the global network dynamics. It consists in (1) finding the states of the network
      that are most frequently visited and (2) the identification of variable and
      frozen nodes of the network. The method, along with a simulation that includes
      random features, is applied to the study of stomata closure by abscisic acid
      (ABA) in A. thaliana proposed by Albert and coworkers. RESULTS: We find that for
      the case of study, that the dynamics of wild and mutant networks have just two
      states that are highly visited in their space of states and about a third of all
      nodes of the wild network are variable while the rest remain frozen in True or
      False states. This high number of frozen elements explains the low cardinality of
      the space of states of the wild network. Similar results are observed in the
      mutant networks. The application of the method allowed us to explain how wild and
      mutants behave dynamically in the SS and determined an essential feature of the
      activation of the closure node (representing stomata closure), i.e. its
      synchronization with the AnionEm node (representing anion efflux at the plasma
      membrane). The dynamics of this synchronization explains the efficiency reached
      by the wild and each of the mutant networks. CONCLUSIONS: For the biological
      problem analyzed, our method allows determining how wild and mutant networks
      differ 'phenotypically'. It shows that the different efficiencies of stomata
      closure reached among the simulated wild and mutant networks follow from a
      dynamical behavior of two nodes that are always synchronized. Additionally, we
      predict that the involvement of the anion efflux at the plasma membrane is
      crucial for the plant response to ABA. AVAILABILITY: The algorithm used in the
      simulations is available upon request.

PMID- 22369582
TI  - miRNA arm selection and isomiR distribution in gastric cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-protein-coding RNAs. miRNA genes
      need several biogenesis steps to form function miRNAs. However, the precise
      mechanism and biology involved in the mature miRNA molecules are not clearly
      investigated. In this study, we conducted in-depth analyses to examine the arm
      selection and isomiRs using NGS platform. METHODS: We sequenced small RNAs from
      one pair of normal and gastric tumor tissues with Solexa platform. By analyzing
      the NGS data, we quantified the expression profiles of miRNAs and isomiRs in
      gastric tissues. Then, we measured the expression ratios of 5p arm to 3p arm of
      the same pre-miRNAs. And, we used Kolmogorov-Smirnov (KS) test to examine isomiR
      pattern difference between tissues. RESULTS: Our result showed the 5p arm and 3p
      arm miRNA derived from the same pre-miRNAs have different tissue expression
      preference, one preferred normal tissue and the other preferred tumor tissue,
      which strongly implied that there could be other mechanism controlling mature
      miRNA selection in addition to the known hydrogen-bonding selection rule.
      Furthermore, by using the KS test, we demonstrated that some isomiR types
      preferentially occur in normal gastric tissue but other types prefer tumor
      gastric tissue. CONCLUSIONS: Arm selections and isomiR patterns are significantly
      varied in human cancers by using deep sequencing NGS data. Our results provided a
      novel research topic in miRNA regulation study. With advanced bioinformatics and
      molecular biology studies, more robust conclusions and insight into miRNA
      regulation can be achieved in the near future.

PMID- 22369580
TI  - Hydrodynamic and functional analysis of HIV-1 Vif oligomerization.
AB  - HIV-1 Vif is an accessory protein that induces the proteasomal degradation of the
      host restriction factor, apolipoprotein B mRNA-editing enzyme catalytic
      polypeptide-like 3G (APOBEC3G). The N-terminal half of Vif binds to APOBEC3G, and
      the C-terminal half binds to subunits of a cullin 5-based ubiquitin ligase. This
      Vif-directed ubiquitin ligase induces the degradation of APOBEC3G (a cytidine
      deaminase) and thereby protects the viral genome from mutation. A conserved PPLP
      motif near the C-terminus of Vif is essential for Vif function and is also
      involved in Vif oligomerization. However, the mechanism and functional
      significance of Vif oligomerization is unclear. We employed analytical
      ultracentrifugation to examine the oligomeric properties of Vif in solution.
      Contrary to previous reports, we find that Vif oligomerization does not require
      the conserved PPLP motif. Instead, our data suggest a more complex mechanism
      involving interactions among the HCCH motif, the BC box, and downstream residues
      in Vif. Mutation of residues near the PPLP motif (S165 and V166) affected the
      oligomeric properties of Vif and weakened the ability of Vif to bind and induce
      the degradation of APOBEC3G. We propose that Vif oligomerization may represent a
      mechanism for regulating interactions with APOBEC3G.

PMID- 22369584
TI  - Real-time surface-enhanced Raman spectroscopy monitoring of surface pH during
      electrochemical melting of double-stranded DNA.
AB  - The application of a negative potential ramp at a double-stranded DNA (dsDNA)
      functionalized electrode surface results in the gradual denaturation of the DNA
      in a process known as electrochemical melting. The underlying physical chemistry
      behind electrochemically driven DNA denaturation is not well understood, and one
      possible mechanism is a change in local pH at the electrode surface. We
      demonstrate that by coimmobilization of p-mercaptobenozic acid at a dsDNA
      functionalized electrode surface, it is possible to monitor both DNA denaturation
      and the local pH simultaneously using surface-enhanced Raman spectroscopy. We
      find that the local pH at the electrode surface does not change as the applied
      potential is scanned negative and the dsDNA denatures. We therefore conclude that
      in these experiments electrochemical melting is not caused by electrochemically
      driven local pH changes.

PMID- 22369583
TI  - Measuring women's perceived ability to overcome barriers to healthcare seeking in
      Burkina Faso.
AB  - BACKGROUND: In sub-Saharan Africa, women must overcome numerous barriers when
      they need modern healthcare. Respect of gender norms within the household and the
      community may still influence women's ability to obtain care. A lack of gender
      sensitive instruments for measuring women's ability to overcome barriers
      compromises attempts to adequately quantify the burden and risk of exclusion they
      face when seeking modern healthcare. The aim of this study was to create and
      validate a synthetic measure of women's access to healthcare from a publicly
      available and possibly internationally comparable population-based survey.
      METHOD: Seven questionnaire items from the Burkina Faso 2003 DHS were combined to
      create the index. Cronbach's alpha coefficient was used to test the reliability
      of the index. Exploratory factor analyses (EFA) and confirmatory factor analyses
      (CFA) were applied to evaluate the factorial structure and construct validity of
      the index while taking into account the hierarchical structure of the data.
      RESULTS: The index has a Cronbach's alpha of 0.75, suggesting adequate
      reliability. In EFA, three correlated factors fitted the data best. In CFA, the
      construct of perceived ability to overcome barriers to healthcare seeking emerged
      as a second-order latent variable with three domains: socioeconomic barriers,
      geographical barriers and psychosocial barriers. Model fit indices support the
      index's global validity for women of reproductive age in Burkina Faso. Evidence
      for construct validity comes from the finding that women's index scores increase
      with household living standard. CONCLUSION: The DHS items can be combined into a
      reliable and valid, gender-sensitive index quantifying reproductive-age women's
      perceived ability to overcome barriers to healthcare seeking in Burkina Faso. The
      index complies conceptually with the sector-cross-cutting capability approach and
      enables measuring directly the perceived access to healthcare. Therefore it can
      help to improve the design and evaluation of interventions that aim to facilitate
      healthcare seeking in this country. Further analyses may examine how far the
      index applies to similar contexts.

PMID- 22369585
TI  - XPS investigation of a CdS-based photoresistor under working conditions: operando
      XPS.
AB  - A noncontact chemical and electrical measurement X-ray photoelectron spectroscopy
      (XPS) technique is performed to investigate a CdS-based photoresistor during its
      operation. The main objective of the technique is to trace chemical- and location
      specified surface potential variations as shifts of the XPS Cd 3d(5/2) peak
      position without and under photoillumination with four different lasers. The
      system is also modeled to extract electrical information. By analyzing the
      measured potential variations with this model, location-dependent resistance
      values are represented (i) two dimensionally for line scans and (ii) three
      dimensionally for areal measurements. In both cases, one of the dimensions is the
      binding energy. The main advantage of the technique is its ability to assess an
      element-specific surface electrical potential of a device under operation based
      on the energy deviation of core level peaks in surface domains. Detection of the
      variations in electrical potentials and especially their responses to the energy
      of the illuminating source in operando, is also shown to be capable of detecting,
      locating, and identifying the chemical nature of structural and other types of
      defects.

PMID- 22369586
TI  - Regioselective glycosylation method using partially protected arabino- and
      galactofuranosyl thioglycosides as key glycosylating substrates and its
      application to one-pot synthesis of oligofuranoses.
AB  - We describe in this paper the development of a novel regioselective
      furanosylation methodology using partially protected furanosyl thioglycosides as
      central glycosylating building blocks and its application in the efficient one
      pot synthesis of a series of linear and branched-type arabino- and
      galactofuranoside fragments structurally related to the cell wall polysaccharides
      of  Mycobacterium tuberculosis ,  Streptococcus pneumoniae  serostype 35A, and
      sugar beet.

PMID- 22369587
TI  - Identification of nucleotide patterns enriched in secreted RNAs as putative cis
      acting elements targeting them to exosome nano-vesicles.
AB  - BACKGROUND: Exosomes are nanoscale membrane vesicles released by most cells. They
      are postulated to be involved in cell-cell communication and genetic
      reprogramming of their target cells. In addition to proteins and lipids, they
      release RNA molecules many of which are not present in the donor cells implying a
      highly selective mode of their packaging into these vesicles. Sequence motifs
      targeting RNA to the vesicles are currently unknown. RESULTS: Ab initio approach
      was applied for computational identification of potential RNA secretory motifs in
      the primary sequences of exosome-enriched RNAs (eRNAs). Exhaustive motif analysis
      for the first time revealed unique sequence features of eRNAs. We discovered
      multiple linear motifs specifically enriched in secreted RNAs. Their potential
      function as cis-acting elements targeting RNAs to exosomes is proposed. The
      motifs co-localized in the same transcripts suggesting combinatorial organization
      of these secretory signals. We investigated associations of the discovered motifs
      with other RNA parameters. Secreted RNAs were found to have almost twice shorter
      half-life times on average, in comparison with cytoplasmic RNAs, and the
      occurrence of some eRNA-specific motifs significantly correlated with this eRNA
      feature. Also, we found that eRNAs are highly enriched in long noncoding RNAs.
      CONCLUSIONS: Secreted RNAs share specific sequence motifs that may potentially
      function as cis-acting elements targeting RNAs to exosomes. Discovery of these
      motifs will be useful for our understanding the roles of eRNAs in cell-cell
      communication and genetic reprogramming of the target cells. It will also
      facilitate nano-scale vesicle engineering and selective targeting of RNAs of
      interest to these vesicles for gene therapy purposes.

PMID- 22369588
TI  - Learning the structure of gene regulatory networks from time series gene
      expression data.
AB  - BACKGROUND: Dynamic Bayesian Network (DBN) is an approach widely used for
      reconstruction of gene regulatory networks from time-series microarray data. Its
      performance in network reconstruction depends on a structure learning algorithm.
      REVEAL (REVerse Engineering ALgorithm) is one of the algorithms implemented for
      learning DBN structure and used to reconstruct gene regulatory networks (GRN).
      However, the two-stage temporal Bayes network (2TBN) structure of DBN that
      specifies correlation between time slices cannot be obtained by score metrics
      used in REVEAL. METHODS: In this paper, we study a more sophisticated score
      function for DBN first proposed by Nir Friedman for stationary DBNs structure
      learning of both initial and transition networks but has not yet been used for
      reconstruction of GRNs. We implemented Friedman's Bayesian Information Criterion
      (BIC) score function, modified K2 algorithm to learn Dynamic Bayesian Network
      structure with the score function and tested the performance of the algorithm for
      GRN reconstruction with synthetic time series gene expression data generated by
      GeneNetWeaver and real yeast benchmark experiment data. RESULTS: We implemented
      an algorithm for DBN structure learning with Friedman's score function, tested it
      on reconstruction of both synthetic networks and real yeast networks and compared
      it with REVEAL in the absence or presence of preprocessed network generated by
      Zou&Conzen's algorithm. By introducing a stationary correlation between two
      consecutive time slices, Friedman's score function showed a higher precision and
      recall than the naive REVEAL algorithm. CONCLUSIONS: Friedman's score metrics for
      DBN can be used to reconstruct transition networks and has a great potential to
      improve the accuracy of gene regulatory network structure prediction with time
      series gene expression datasets.

PMID- 22369589
TI  - Case study of cognitive behavioural therapy awareness educational programme using
      blended learning, UK.
AB  - This paper examined the opportunities as well as challenges in relation to the
      use of cognitive behavioural therapy (CBT). The opportunities include the
      increased range of mental health conditions and other disorders where CBT (in
      isolation or with other interventions) could be effective to address them, as
      well as policies around workforce education and training that support the
      expansion of psychological therapies, particularly CBT services. The challenges
      include the urgent need of heightened awareness among the wider platform of
      health and social care workers about CBT principles, structure, framework,
      methods of delivery, wider applications, evaluation and appropriate referral of
      clients, and stepped model of care. In response to such needs, the paper
      described CBT awareness educational award at the University of Gloucestershire,
      UK: the Certificate of Professional Studies in Awareness of Cognitive and
      Behavioural Therapies Practice delivered at Level III and M level. The challenges
      associated with the initiation and running of such educational programmes are
      highlighted, as well as suggestions for the way forward considering the
      learners', employers' and educational providers' perspectives.

PMID- 22369590
TI  - Change in antimicrobial susceptibility of  Escherichia coli  urinary tract
      isolates at a single institution over a period of 10 years.
AB  - Urinary tract infections are common. Few published studies have demonstrated the
      change in Escherichia coli urinary isolate antimicrobial susceptibility over time
      within a given area and (or) population. The purpose of this study was to
      evaluate the change in susceptibility of E. coli clinical isolates obtained from
      urine specimens at a single institution over a period of 10 years. The
      microbiology laboratory information system at St. Boniface Hospital (Winnipeg,
      Manitoba, Canada) was searched retrospectively from 1 January 2000 to 31 December
      2009, for all E. coli isolates from either a midstream or catheter urine source
      that had susceptibility testing performed. Only one isolate per patient was
      included during the entire study period. Antimicrobial susceptibility testing was
      carried out with either a Microscan instrument (pre-April 2004) or a Vitek
      instrument (May 2004 onwards). In total, 7353 E. coli urinary isolates were
      included for evaluation. Ciprofloxacin susceptibility declined significantly,
      from 99% in 2000 to 85% in 2009 (p < 0.0001). A small but statistically
      significant decline in susceptibility was also observed for ampicillin,
      cefazolin, trimethoprim-sulfamethoxazole, gentamicin, and nitrofurantoin. These
      data suggest that certain antimicrobials recommended for the treatment of urinary
      tract infections (ciprofloxacin, trimethoprim-sulfamethoxazole) may no longer be
      optimal.

PMID- 22369592
TI  - Focused clinical campaign improves mineral and bone disorder outcomes.
AB  - As with other disease states, mineral and bone disorder (MBD) management is
      challenging and may benefit from more systematic management. To evaluate the
      effectiveness of a focused campaign to improve MBD outcomes, we compared the
      percentage of patients meeting 2003 Kidney Dialysis Outcomes Quality Initiative
      (KDOQI)-recommended MBD targets between baseline and 18 months after programme
      initiation. The four components of the clinical campaign were: (1) a set of grids
      allowing simultaneous evaluation of MBD test results, (2) a weighted, facility
      level cumulative scoring system representing percent of patients within KDOQI
      recommended MBD targets, (3) team involvement and (4) patient education. Eighteen
      months after programme initiation, the percent of patients simultaneously meeting
      all 2003 KDOQI targets increased 7% and the percent meeting calcium and
      phosphorus targets increased 24% and 8%, respectively. These findings suggest
      that a coordinated clinical campaign with effective tools, outcome tracking and
      sharing and team involvement is an effective strategy to improve MBD outcomes.

PMID- 22369593
TI  - Comparison of fast peritoneal equilibrium test with the standard method: a pilot
      study.
AB  - Standard peritoneal equilibrium test (PET) is an implementation that requires
      hard work for peritoneal dialysis (PD) staff. We analysed the efficacy of the
      fast PET and compared its results with standard PET. Forty-nine patients on PD
      therapy were included in the study. For standard PET, glucose, urea and
      creatinine values of dialysate were analysed at zeroth, second and fourth hours,
      and the patient's serum glucose, urea and creatinine values were analysed at
      second hour. In the fast PET, urea, glucose and creatinine values in plasma and
      dialysate were analysed at the fourth hour only. The results of both methods were
      compared with Pearson correlation and kappa tests. According to the standard PET,
      low transport in five patients, low-average transport in 17 patients, high
      average transport in 23 patients and high transport types in four patients were
      identified. Fast PET results were similar in 46 (94%) patients (r = 0.77, p =
      0.0001). Kappa (kappaw) analysis of results of both PETs was also statistically
      significant (p = 0.0001). This study showed that the peritoneal transport type
      may be determined more easily, practically and faster.

PMID- 22369594
TI  - Adhering to behaviour change in older pre-dialysis populations--what do patients
      think? A qualitative study.
AB  - BACKGROUND: Chronic Kidney Disease (CKD) is associated with the development of
      serious co-morbidities. Patients with CKD are encouraged to adhere to regimens to
      lower this risk. This study aimed to explore the experiences of patients
      attempting to integrate lifestyle changes into their lives. METHOD: Face-to-face
      recorded interviews were conducted with nine consenting patients with CKD Stage 4
      under the care of a consultant nephrologist. Each recording was analysed by two
      independent investigators using thematic analysis. RESULTS: Five themes emerged:
      Self in relation to others, Control, Adherence, Beliefs about treatment and
      illness and Uncertainty. Participants highlighted the importance of personal
      support and recounted their sense of being a burden on close family. They
      described how they approached disclosure about their condition, their beliefs
      regarding treatment and their decision making processes and how these factors
      impacted on adherence to behaviour change. CONCLUSION: Practical support from
      family and healthcare professionals, a willingness to disclose their condition
      and help to make good decisions in difficult circumstances were identified as
      important factors in supporting success with behaviour change.

PMID- 22369595
TI  - Nutritional management of stage 5 chronic kidney disease.
AB  - Nutrition is a critical issue in the management of patients with stage 5 chronic
      kidney disease (CKD). Malnutrition is common among these patients and affects
      their survival and quality of life. A basic knowledge of the nutritional
      management of stage 5 CKD is essential for all members of the nephrology team to
      improve patient care. This paper demonstrates that the needs of haemodialysis
      patients are more complex than those receiving peritoneal dialysis.

PMID- 22369596
TI  - Cholesterol-based nucleolipid-ruthenium complex stabilized by lipid aggregates
      for antineoplastic therapy.
AB  - A novel ruthenium complex, linked to a cholesterol-containing nucleolipid (named
      ToThyCholRu), stabilized by lipid aggregates for antineoplastic therapy is
      presented. In order to retard the degradation kinetics typically observed for
      several ruthenium-based antineoplastic agents, ToThyCholRu is incorporated into a
      liposome bilayer formed by POPC. The resulting nanoaggregates contain up to 15%
      in moles of the ruthenium complex, and are shown to be stable for several weeks.
      The liposomes host the ruthenium-nucleolipid complex with the metal ion
      surrounded by POPC lipid headgroups and the steroid moiety inserted in the more
      external acyl chain region. These ruthenium-containing liposomes are more
      effective in inhibiting the growth of cancer cells than a model NAMI-A-like
      ruthenium complex, prepared for a direct evaluation of their anti-proliferative
      activity. These results introduce new perspectives in the design of innovative
      transition-metal-based supramolecular systems for anticancer drug vectorization.

PMID- 22369597
TI  - In-depth molecular and phenotypic characterization in a rice insertion line
      library facilitates gene identification through reverse and forward genetics
      approaches.
AB  - We report here the molecular and phenotypic features of a library of 31,562
      insertion lines generated in the model japonica cultivar Nipponbare of rice
      (Oryza sativa L.), called Oryza Tag Line (OTL). Sixteen thousand eight hundred
      and fourteen T-DNA and 12,410 Tos17 discrete insertion sites have been
      characterized in these lines. We estimate that 8686 predicted gene intervals-
      i.e. one-fourth to one-fifth of the estimated rice nontransposable element gene
      complement--are interrupted by sequence-indexed T-DNA (6563 genes) and/or Tos17
      (2755 genes) inserts. Six hundred and forty-three genes are interrupted by both T
      DNA and Tos17 inserts. High quality of the sequence indexation of the T2 seed
      samples was ascertained by several approaches. Field evaluation under agronomic
      conditions of 27,832 OTL has revealed that 18.2% exhibit at least one
      morphophysiological alteration in the T1 progeny plants. Screening 10,000 lines
      for altered response to inoculation by the fungal pathogen Magnaporthe oryzae
      allowed to observe 71 lines (0.7%) developing spontaneous lesions simulating
      disease mutants and 43 lines (0.4%) exhibiting an enhanced disease resistance or
      susceptibility. We show here that at least 3.5% (four of 114) of these
      alterations are tagged by the mutagens. The presence of allelic series of
      sequence-indexed mutations in a gene among OTL that exhibit a convergent
      phenotype clearly increases the chance of establishing a linkage between
      alterations and inserts. This convergence approach is illustrated by the
      identification of the rice ortholog of AtPHO2, the disruption of which causes a
      lesion-mimic phenotype owing to an over-accumulation of phosphate, in nine lines
      bearing allelic insertions.

PMID- 22369598
TI  - Folding of a helix is critically stabilized by polarization of backbone hydrogen
      bonds: study in explicit water.
AB  - Multiple single-trajectory molecular dynamics (MD) simulation at room temperature
      (300 K) in explicit water was carried out to study the folding dynamics of an
      alpha-helix (PDB 2I9M ) using a polarized charge scheme that includes electronic
      polarization of backbone hydrogen bonds. Starting from an extended conformation,
      the 17-residue peptide was successfully folded into the native structure (alpha
      helix) between 80 and 130 ns with a root-mean-square deviation of ~1.0 A.
      Analysis of the time-dependent trajectories revealed that helix formation of the
      peptide started at the terminals and progressed toward the center of the peptide.
      For comparison, MD trajectories generated under various versions of standard
      AMBER force fields failed to show any significant or stable helix formation in
      our simulation. Our result shows clear evidence that the electronic polarization
      of backbone hydrogen bonds energetically stabilizes the helix formation and is
      critical to the stable folding of the short helix structure.

PMID- 22369599
TI  - Mothering a Birth manuscript: from submission to publication.

PMID- 22369600
TI  - The term breech trial ten years on: primum non nocere?
AB  - In 2000, the Term Breech Trial was published, and its authors recommended
      cesarean section as the safest mode of delivery for breech-presenting babies.
      Criticisms of the trial were raised at the time, which the authors dismissed.
      Since then, maternal deaths have been recorded among women undergoing cesarean
      sections for breech presentations. Accordingly, those initial criticisms deserve
      to be revisited.

PMID- 22369601
TI  - Fetal movement counting--maternal concern and experiences: a multicenter,
      randomized, controlled trial.
AB  - BACKGROUND: Fetal movement counting may improve timely identification of
      decreased fetal activity and thereby contribute to prevent adverse pregnancy
      outcomes, but it may also contribute to maternal concern. This study aimed to
      test whether fetal movement counting increased maternal concern. METHODS: In a
      multicenter, controlled trial 1,013 women with a singleton pregnancy were
      randomly assigned either to perform daily fetal movement counting from pregnancy
      week 28 or to follow standard Norwegian antenatal care where fetal movement
      counting is not encouraged. The primary outcome was maternal concern, measured by
      the Cambridge Worry Scale. Analysis was by intention-to-treat. RESULTS: The means
      and SDs on Cambridge Worry Scale scores were 0.77 (0.55) and 0.90 (0.62) for the
      intervention and the control groups, respectively, a mean difference between the
      groups of 0.14 (95% CI: 0.06-0.21, p<0.001). Decreased fetal activity was of
      concern to 433 women once or more during pregnancy, 45 and 42 percent in the
      intervention and control groups, respectively (relative risk=1.1, 95% CI: 0.9
      1.2). Seventy-nine percent of the women responded favorably to the use of
      counting charts. CONCLUSIONS: Women who performed fetal movement counting in the
      third trimester reported less concern than those in the control group. The
      frequency of maternal report of concern about decreased fetal activity was
      similar between the groups. Most women considered the use of a counting chart to
      be positive.

PMID- 22369602
TI  - Learning the hard way: expectations and experiences of infant feeding support.
AB  - BACKGROUND: Breastfeeding involves learning for women and their infants. For
      emotional, social, and developmental reasons this type of feeding is recommended
      for all newborn infants but for those in exceptional circumstances. The objective
      of this study was to gain a better understanding of what is needed in the early
      days to enable women to initiate and continue breastfeeding their infants.
      METHODS: Data from a large-scale national survey of women's experience of
      maternity care in England were analyzed using qualitative methods, focusing on
      the feeding-related responses. RESULTS: A total of 2,966 women responded to the
      survey (62.7% response rate), 2,054 of whom wrote open text responses, 534
      relating to infant feeding. The main themes identified were "the mismatch between
      women's expectations and experiences" and "emotional reactions" at this time,
      "staff behavior and attitudes," and "the organization of care and facilities."
      Subthemes related to seeking help, conflicting advice, pressure to breastfeed,
      the nature of interactions with staff, and a lack of respect for women's choices,
      wishes, previous experience, and knowledge. CONCLUSIONS: Many women who succeeded
      felt that they had "learned the hard way" and some of those who did not, felt
      they were perceived as "bad mothers" and women who had in some way "failed" at
      one of the earliest tasks of motherhood. What women perceived to be staff
      perceptions affected how they saw themselves and what they took away from their
      early experience of infant feeding.

PMID- 22369603
TI  - Women's experiences of participating in the early external cephalic version 2
      trial.
AB  - BACKGROUND: The international, multicenter External Cephalic Version 2 (ECV2)
      Trial compared early external cephalic version at 34(0/7) to 35(6/7) weeks with
      that at greater than 37 weeks. A total of 1,543 women were randomized from 68
      centers in 21 countries. The goal of this component of the trial was to
      understand women's views about participation in a research trial and timing of
      external cephalic version. METHODS: A postpartum questionnaire was completed
      containing a 5-point Likert scale examining contact and availability of staff,
      choice of timing of external cephalic version, preference of randomization,
      convenience of participating, and overall satisfaction. Participants also
      completed two open-ended questions related to timing of external cephalic version
      and satisfaction with the trial. Descriptive statistics and content analysis were
      used to analyze data. RESULTS: A total of 1,458 women completed the
      questionnaire, of whom 86 percent said "yes"-they would participate in the trial
      again. Themes influencing decisions about participating were perceptions of the
      external cephalic version experience, preferred mode of delivery, preferred
      timing of external cephalic version, and perceptions of the effectiveness of
      external cephalic version and of the trial environment. Many participants
      preferred the early timing of the procedure offered through the trial because of
      perceived advantages of a smaller baby being easier to turn and the opportunity
      for repeat procedures. CONCLUSIONS: Women were positive about their participation
      in the trial. Early external cephalic version was preferred over the traditional
      timing as it was perceived to afford both physiologic and practical advantages.

PMID- 22369604
TI  - Requesting cesareans without medical indications: an option being considered by
      young canadian women.
AB  - BACKGROUND: Cesarean delivery on maternal request is a worldwide growing
      phenomenon. The goal of this study was to describe young nulliparous women's
      attitudes about cesarean delivery on maternal request. METHODS: A total of 140
      nulliparous women in Canada aged between 18 and 24years and attending school from
      the vocational (n=53), college (n=61), and university (n=18) levels (n=8 other)
      participated in the survey. The self-administered questionnaire consisted of 23
      open-ended questions. The outcome measure was the participant's attitude toward
      cesarean delivery on maternal request. Descriptive, bivariate, and multiple
      regression analyses were performed. RESULTS:   Many of the respondents (63%) had
      previously heard about cesarean delivery on maternal request, and of these women
      28.6 percent had a favorable attitude toward the procedure. Sociodemographic
      variables were not associated with participants' attitudes toward cesarean
      delivery on maternal request except for place of residence and type of
      professional preferred for pregnancy care. Thinking that vaginal birth was more
      painful than cesarean delivery (p=0.012) and had more consequences for the mother
      (p<0.001) were related to a positive attitude toward cesarean delivery on
      maternal request. A positive attitude by peers was also associated with
      participants' favorable attitude toward cesarean delivery on maternal request
      (p<0.001). The overall predictive success of the model was 66.5 percent.
      CONCLUSIONS: Young women are spreading the word about cesarean delivery on
      maternal request and may influence one another about their preferred delivery
      method. During prenatal visits practitioners need to address women's fear of
      vaginal birth and its consequences for the mother, counseling, and women's
      understanding of the consequences of cesarean delivery. This study supports the
      urgent need to systematically document cesarean delivery on maternal request as a
      medical procedure and to study its prevalence and related factors.

PMID- 22369605
TI  - Web-based news reports on midwives compared with obstetricians: a prospective
      analysis.
AB  - BACKGROUND: The media both creates and reflects public opinion. The way in which
      health professionals are depicted in the media is likely to influence views held
      by and about different health professions. The aim of this study was to examine
      how midwives and obstetricians are reported in English language web-based news
      reports from around the world. METHODS: News alerts from the Internet search
      engine Google were created to search for the terms
      "midwife,""midwives,""midwifery,""obstetrics," and "obstetricians." These alerts
      were received over a 12-month period (May 1, 2006-April 31, 2007), downloaded,
      and analyzed using quantitative content analysis. RESULTS: A total of 522 web
      based news reports for midwifery and 564 for obstetrics (n = 1,086) were found.
      Dominant categories for midwives were: "mainstreaming midwives" (models of
      care/rise of midwifery) (28%); "the Cinderella of the maternity care"
      (workforce/industrial) (27%); "delivering the baby with your hands tied"
      (funding, insurance, and legislation) (21%); "ask the expert" (education,
      research, and health advice) (8%), "recognizing midwives" (awards and
      announcements) (7%), "unsafe midwives" (litigation) (6%); and "the art of birth"
      (books, film, and photographs) (2%). Dominant categories for obstetricians were:
      "ask the expert" (research and advice) (26%); "doctors are heroes amongst us"
      (awards and announcements) (19%); "obstetric workforce woes"
      (workforce/industrial) (19%); "new frontiers" (trends in care and new technology)
      (17%); "the disappearing obstetrician" (insurance and litigation) (10%); and
      "human-interest news reports" (9%). Obstetricians were more likely to be
      recognized as experts on pregnancy and birth and receive public recognition
      compared with midwives. Midwives were more likely to be depicted as struggling to
      be a mainstream option while being hampered by lack of funding, insurance, and
      legislative barriers. CONCLUSIONS: Although midwives have rising acceptance, they
      still struggle with recognition. Obstetricians have both acceptance and
      recognition. Countries where midwifery is a mainstream option have more news
      reports related to midwifery than obstetrics. Different issues appear more
      dominant in some countries, such as work force in the United Kingdom and funding,
      insurance, and legislation in the United States.

PMID- 22369606
TI  - Perinatal postmortems: what is important to parents and how do they decide?
AB  - BACKGROUND: Falling consent rates for postmortems, regardless of age of death,
      have been widely reported in recent years. The aim of this study was to explore
      parental attitudes to, and decision-making about, a perinatal postmortem after
      termination for fetal abnormality, late miscarriage, or stillbirth. METHODS: A
      prospective self-completion questionnaire was given to 35 women and their
      partners. The participants had experienced second or third trimester pregnancy
      loss in a single fetal medicine and delivery unit in the United Kingdom and were
      making decisions about having a postmortem. They were asked to complete a
      questionnaire about their attitudes to, and expectations of, a perinatal
      postmortem. RESULTS: Thirty-one questionnaires were received from parents of 17
      babies (49% of those asked; 16 from mothers, 15 from fathers). Parents of nine
      babies (53%) said they would agree to a full postmortem, of three babies to a
      limited postmortem, and of four babies to an external examination only; one
      couple were undecided. The most important issues for the parents in this study
      that related to their decisions about a postmortem centered on the need for
      information, both for future planning and about what had happened. Moderately
      important issues related to altruism, which is, improving medical knowledge and
      helping other parents experiencing similar bereavement. Among the lowest scoring
      issues were potential barriers, such as concerns about cultural or religious
      acceptability of a postmortem, funeral delays, and what would happen to the
      baby's body. CONCLUSIONS: Bereaved parents who participated in this study, where
      postmortem consent rates were relatively high, thought that their need for
      knowledge eclipsed assumed barriers when deciding whether or not to have a
      postmortem for their baby.

PMID- 22369607
TI  - A qualitative study of postpartum mothers' intention to smoke.
AB  - BACKGROUND: Many women stop smoking during pregnancy. Factors associated with
      relapse are known, but no intervention prevents the return to smoking among
      pregnant women. The objective of this study was to determine why women return to
      smoking after prolonged abstinence during pregnancy by examining mothers'
      intention to smoke at the time of delivery and the perceptions that shape their
      intention. METHODS: We conducted in-depth, semi-structured interviews during
      their postpartum hospital stay with 24 women who stopped smoking while pregnant.
      We asked participants whether they intended to resume smoking after pregnancy and
      why. Transcripts were analyzed using grounded theory-based qualitative methods to
      identify themes. RESULTS: Participants ranged in age from 18 to 36 years, and 63
      percent were white. Three themes emerged from the interviews with the mothers: 1)
      they did not intend to return to smoking but doubted whether they would be able
      to maintain abstinence; 2) they believed that it would be possible to protect
      their newborns from the harms of cigarette smoke; and 3) they felt that they had
      control over their smoking and did not need help to maintain abstinence after
      pregnancy. CONCLUSIONS: Although most participants did not intend to resume
      smoking, their intentions may be stymied by their perceptions about second-hand
      smoke and by their overestimation of their control over smoking. Further study
      should quantify these barriers and determine their evolution over the first year
      after pregnancy with the goal of informing more successful, targeted
      interventions.

PMID- 22369608
TI  - The patient observer: eye-movement desensitization and reprocessing for the
      treatment of posttraumatic stress following childbirth.
AB  - BACKGROUND: No standard intervention with proved effectiveness is available for
      women with posttraumatic stress following childbirth because of insufficient
      research. The objective of this paper was to evaluate the possibility of using
      eye-movement desensitization and reprocessing treatment for women with symptoms
      of posttraumatic stress disorder following childbirth. The treatment is
      internationally recognized as one of the interventions of choice for the
      condition, but little is known about its effects in women who experienced the
      delivery as traumatic. METHODS: Three women suffering from posttraumatic stress
      symptoms following the birth of their first child were treated with eye-movement
      desensitization and reprocessing during their next pregnancy. Patient A developed
      posttraumatic stress symptoms following the lengthy labor of her first child that
      ended in an emergency cesarean section after unsuccessful vacuum extraction.
      Patient B suffered a second degree vaginal rupture, resulting in pain and
      inability to engage in sexual intercourse for years. Patient C developed severe
      preeclampsia postpartum requiring intravenous treatment. RESULTS: Patients
      received eye-movement desensitization and reprocessing treatment during their
      second pregnancy, using the standard protocol. The treatment resulted in fewer
      posttraumatic stress symptoms and more confidence about their pregnancy and
      upcoming delivery compared with before the treatment. Despite delivery
      complications in Patient A (secondary cesarean section due to insufficient
      engaging of the fetal head); Patient B (second degree vaginal rupture, this time
      without subsequent dyspareunia); and Patient C (postpartum hemorrhage, postpartum
      hypertension requiring intravenous treatment), all three women looked back
      positively at the second delivery experience. CONCLUSIONS: Treatment with eye
      movement desensitization and reprocessing reduced posttraumatic stress symptoms
      in these three women. They were all sufficiently confident to attempt vaginal
      birth rather than demanding an elective cesarean section. We advocate a large
      scale, randomized controlled trial involving women with postpartum posttraumatic
      stress disorder to evaluate the effect of eye-movement desensitization and
      reprocessing in this patient group.

PMID- 22369609
TI  - Has pseudocyesis become an outmoded diagnosis?

PMID- 22369610
TI  - The tyranny of meta-analysis and the misuse of randomized controlled trials in
      maternity care.
AB  - Recent meta-analyses of key areas in maternity care have covered home birth and
      epidural analgesia. In each of these cases serious issues have arisen from the
      use of subjective inclusion and exclusion criteria, heterogeneity of included
      studies, and inclusion of studies that were conducted in settings that were not
      representative of usual maternity care. This latter flaw is especially notable
      for early epidural analgesia, where study environments with very low cesarean
      section rates are included. Such study settings lack external validity and have
      raised concerns about the political uses of meta-analysis. For a meta-analysis to
      be useful, the included studies must be broadly representative of the way that
      maternity care is carried out in usual birth environments.

PMID- 22369615
TI  - 8-Vinylguanine nucleo amino acid: a fluorescent PNA building block.
AB  - Attachment of a vinyl group at guanine position 8 provides fluorescent properties
      of the nucleobase. Therefore, 8-vinylguanine was introduced as a 2
      aminoethylglycine peptide nucleic acid (PNA) building block. Incorporation of the
      guanine analog in short PNA sequences by Fmoc solid phase peptide synthesis
      allowed the differentiation between hybridization states of specific double
      strands with DNA, RNA, and PNA as well as quadruplex forming RNA/PNA oligomers
      based on fluorescence intensity.

PMID- 22369616
TI  - A special issue on DNA damage response and genome stability.

PMID- 22369618
TI  - First premolar extraction effects on upper airway dimension in bimaxillary
      proclination patients.
AB  - OBJECTIVE: To determine how orthodontic treatment with first premolar teeth
      extracted and the associated arch dimensional changes in bimaxillary proclination
      patients affect the upper airway dimensions. MATERIALS AND METHODS: Pre- and
      postorthodontic treatment cephalograms and dental casts of 40 bimaxillary
      proclination patients (ages ranged between 18 and 23 years) were used for this
      study. Patients were all treated with extraction of the four first premolars.
      Cephalometric radiographs were used to measure airway dimensions, and dental
      casts were used to measure the changes in the arch dimensions. A paired t-test
      was used to detect differences at P < .05. RESULTS: The results showed
      statistically significant reductions in tongue length (P < .05), posterior
      adenoids thickness (AD2-H) (P < .05), upper and lower incisor inclination, and
      lower incisor to A-Pog line (P < .001). Considering the dental cast results,
      statistically significant reductions in upper arch length, lower arch length, and
      lower intermolar width were also found (P < .001). The only statistically
      significant increase was recorded for the upper intercanine width (P < .001).
      CONCLUSIONS: Extraction of the first premolars for the treatment of bimaxillary
      proclination does not affect upper airway dimensions despite the significant
      reduction in tongue length and arch dimensions.

PMID- 22369617
TI  - Electrostatics of nucleic acid folding under conformational constraint.
AB  - RNA folding is enabled by interactions between the nucleic acid and its ion
      atmosphere, the mobile sheath of aqueous ions that surrounds and stabilizes it.
      Understanding the ion atmosphere requires the interplay of experiment and theory.
      However, even an apparently simple experiment to probe the ion atmosphere,
      measuring the dependence of DNA duplex stability upon ion concentration and
      identity, suffers from substantial complexity, because the unfolded ensemble
      contains many conformational states that are difficult to treat accurately with
      theory. To minimize this limitation, we measured the unfolding equilibrium of a
      DNA hairpin using a single-molecule optical trapping assay, in which the unfolded
      state is constrained to a limited set of elongated conformations. The unfolding
      free energy increased linearly with the logarithm of monovalent cation
      concentration for several cations, such that smaller cations tended to favor the
      folded state. Mg(2+) stabilized the hairpin much more effectively at low
      concentrations than did any of the monovalent cations. Poisson-Boltzmann theory
      captured trends in hairpin stability measured for the monovalent cation
      titrations with reasonable accuracy, but failed to do so for the Mg(2+)
      titrations. This finding is consistent with previous work, suggesting that
      Poisson-Boltzmann and other mean-field theories fail for higher valency cations
      where ion-ion correlation effects may become significant. The high-resolution
      data herein, because of the straightforward nature of both the folded and the
      unfolded states, should serve as benchmarks for the development of more accurate
      electrostatic theories that will be needed for a more quantitative and predictive
      understanding of nucleic acid folding.

PMID- 22369619
TI  - The use of different analgesics in orthodontic tooth movements.
AB  - OBJECTIVE: To provide a semi-quantitative assessment of the effect of different
      analgesics (celecoxib, ketorolac, and paracetamol) on tooth movement and bone
      resorption using immunohistochemical staining of matrix metalloproteinase-13 (MMP
      13). MATERIALS AND METHODS: Forty white male rats (12-weeks old; body weight: 230
      250 g) were divided into four groups (10 rats each) and were given the treatment
      once a day for 2 consecutive months. Group A (control group) rats were given the
      reverse osmosis water; group B rats were given 10 mg/kg celecoxib; group C rats
      were given 3 mg/kg ketorolac; and group D rats were given 150 mg/kg paracetamol.
      A precalibrated closed Sentalloy coil spring was placed inside each rat mouth to
      deliver a constant force of 50 cN. The magnitude of tooth movement was measured
      intraorally. After 2 months, the rats were sacrificed, and the sections were
      mounted on L-polylysine-coated glass slides. Slides from each specimen were
      stained with hematoxylin and eosin, and others were stained with MMP-13. Data
      were analyzed with the one-way analysis of variance (ANOVA). RESULTS: Celecoxib,
      ketorolac, and paracetamol groups showed tooth movement of 1.81 +/- 0.43 mm, 1.13
      +/- 0.28 mm, and 1.08 +/- 0.27 mm, respectively. The mean number of MMP-13
      positive osteoclasts was highest in celecoxib-treated group followed by the
      control group and was decreased in the ketorolac and paracetamol groups.
      Comparing all groups to the control revealed significant differences (P < .05).
      CONCLUSION: Administration of celecoxib did not reduce bone resorption or
      interfere with tooth movement in rats compared to other analgesics tested
      (ketorolac and paracetamol).

PMID- 22369620
TI  - Role of in silico genotoxicity tools in the regulatory assessment of
      pharmaceutical impurities.
AB  - The toxicological assessment of genotoxic impurities is important in the
      regulatory framework for pharmaceuticals. In this context, the application of
      promising computational methods (e.g. Quantitative Structure-Activity
      Relationships (QSARs), Structure-Activity Relationships (SARs) and/or expert
      systems) for the evaluation of genotoxicity is needed, especially when very
      limited information on impurities is available. To gain an overview of how
      computational methods are used internationally in the regulatory assessment of
      pharmaceutical impurities, the current regulatory documents were reviewed. The
      software recommended in the guidelines (e.g. MCASE, MC4PC, Derek for Windows) or
      used practically by various regulatory agencies (e.g. US Food and Drug
      Administration, US and Danish Environmental Protection Agencies), as well as
      other existing programs were analysed. Both statistically based and knowledge
      based (expert system) tools were analysed. The overall conclusions on the
      available in silico tools for genotoxicity and carcinogenicity prediction are
      quite optimistic, and the regulatory application of QSAR methods is constantly
      growing. For regulatory purposes, it is recommended that predictions of
      genotoxicity/carcinogenicity should be based on a battery of models, combining
      high-sensitivity models (low rate of false negatives) with high-specificity ones
      (low rate of false positives) and in vitro assays in an integrated manner.

PMID- 22369621
TI  - Hsp90 depletion goes wild.
AB  - Hsp90 reveals phenotypic variation in the laboratory, but is Hsp90 depletion
      important in the wild? Recent work from Chen and Wagner in BMC Evolutionary
      Biology has discovered a naturally occurring Drosophila allele that downregulates
      Hsp90, creating sensitivity to cryptic genetic variation. Laboratory studies
      suggest that the exact magnitude of Hsp90 downregulation is important. Extreme
      Hsp90 depletion might reactivate transposable elements and/or induce aneuploidy,
      in addition to revealing cryptic genetic variation. See research article
      http://wwww.biomedcentral.com/1471-2148/12/25.

PMID- 22369622
TI  - Discrimination of Trichophyton tonsurans and Trichophyton equinum by PCR-RFLP and
      by beta-tubulin and translation elongation factor 1-alpha sequencing.
AB  - Trichophyton tonsurans and T. equinum are two closely related sister species of
      dermatophytes, but differ in their preferred hosts, i.e., humans or horses,
      respectively. Routine procedures for their identification depend on studies of
      their phenotypic, physiological and biochemical characteristics, which are
      laborious and may yield ambiguous results. Molecular methods using rDNA ITS also
      had been judged to be insufficiently discriminatory. In the present study two
      genetic markers were sequenced in addition to the ITS region, i.e., partial beta
      tubulin (BT2) and translation elongation factor 1-alpha (TEF1). The TEF1 locus
      revealed a consistent differences in a 13 bp indel and an additional SNP between
      the two species, along with a single base substitution in BT2 and one ITS1,
      enabling unambiguous distinction of the two taxa. RFLP targeting the ITS region
      was evaluated as a potential tool for routine screening of suspected isolates of
      T. tonsurans and T. equinum.

PMID- 22369623
TI  - First case of breakthrough pneumonia due to Aspergillus nomius in a patient with
      acute myeloid leukemia.
AB  - We report the first known case of a breakthrough pulmonary infection caused by
      Aspergillus nomius in an acute myeloid leukemia patient receiving caspofungin
      therapy. The isolate was identified using matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and sequencing-based
      methods. The organism was found to be fully susceptible, in vitro, to
      echinocandin antifungal agents.

PMID- 22369624
TI  - Yeast vaginitis during pregnancy: susceptibility testing of 13 antifungal drugs
      and boric acid and the detection of four virulence factors.
AB  - A higher prevalence of vulvovaginal candidiasis (VVC) is seen in pregnant women
      compared with those who are not pregnant. Recurrence is also more common in
      pregnant women, and therapeutic responses are reduced. In this investigation, 207
      vaginal yeast isolates recovered from pregnant women were tested for
      susceptibility to 13 antifungal drugs and boric acid and through these studies
      four virulence factors were also determined. The isolates were recovered from
      vaginal samples of patients with acute VVC [AVVC, (n = 73)], symptomatic
      recurrent VVC [RVVC, (n = 89)], asymptomatic RVVC (n = 27), and those without
      signs and symptoms (n = 18). Candida albicans was the most common species found
      (59.9%), followed by C. glabrata (19.8%), other Candida spp., (19.8%), and
      Saccharomyces cerevisiae (0.5%). Antifungal susceptibility testing was performed
      as described in CLSI document M27-A3. Additionally, we examined phospholipase and
      proteinase production, adhesion to vaginal epithelial cells and hemolytic
      activity. Notably, the MIC values of Candida spp. isolates derived from patients
      with VVC were no different from those of the controls (P > 0.05). In addition,
      Candida isolates derived from patients with AVVC or RVVC produced significantly
      higher amounts of phospholipase and proteinase compared with the controls (P <
      0.05). Antifungal testing and the determination of virulence factors may lead to
      the effective and prompt treatment of VVC, particularly in pregnant women.

PMID- 22369625
TI  - Comparison between stearoyl-CoA desaturase expression in milk somatic cells and
      in mammary tissue of lactating dairy cows.
AB  - Stearoyl-CoA desaturase (SCD) is an important enzyme in the bovine mammary gland,
      where it inserts a cis-double bond at the Delta9 position in a wide range of
      fatty acids. Investigating SCD expression in the bovine mammary gland generally
      requires invasive biopsy to obtain mammary tissue. The aim of this study was to
      evaluate the use of milk somatic cells as a non-invasive alternative to biopsy
      for measuring mammary SCD expression in dairy cows. Both milk somatic cells and
      mammary tissue were collected from 14 Holstein-Friesian cows and used for
      analysis of SCD expression by real-time PCR. The SCD5 mRNA levels in mammary
      tissue compared with SCD1 were low, and for several milk somatic cell samples,
      SCD5 expression was even below the limit of detection. A significant relationship
      was found between SCD1 expression in milk somatic cells and in mammary tissue. In
      addition, SCD1 expression in milk somatic cells was significantly related to
      Delta9-desaturase indices in milk, which are commonly used as an indicator of
      SCD1 activity within the mammary gland. Our study showed that milk somatic cells
      can be used as a source of mRNA to study SCD1 expression in dairy cows, offering
      a non-invasive alternative to mammary tissue samples obtained by biopsy.

PMID- 22369626
TI  - CPU-GPU hybrid accelerating the Zuker algorithm for RNA secondary structure
      prediction applications.
AB  - BACKGROUND: Prediction of ribonucleic acid (RNA) secondary structure remains one
      of the most important research areas in bioinformatics. The Zuker algorithm is
      one of the most popular methods of free energy minimization for RNA secondary
      structure prediction. Thus far, few studies have been reported on the
      acceleration of the Zuker algorithm on general-purpose processors or on extra
      accelerators such as Field Programmable Gate-Array (FPGA) and Graphics Processing
      Units (GPU). To the best of our knowledge, no implementation combines both CPU
      and extra accelerators, such as GPUs, to accelerate the Zuker algorithm
      applications. RESULTS: In this paper, a CPU-GPU hybrid computing system that
      accelerates Zuker algorithm applications for RNA secondary structure prediction
      is proposed. The computing tasks are allocated between CPU and GPU for parallel
      cooperate execution. Performance differences between the CPU and the GPU in the
      task-allocation scheme are considered to obtain workload balance. To improve the
      hybrid system performance, the Zuker algorithm is optimally implemented with
      special methods for CPU and GPU architecture. CONCLUSIONS: Speedup of 15.93* over
      optimized multi-core SIMD CPU implementation and performance advantage of 16%
      over optimized GPU implementation are shown in the experimental results. More
      than 14% of the sequences are executed on CPU in the hybrid system. The system
      combining CPU and GPU to accelerate the Zuker algorithm is proven to be promising
      and can be applied to other bioinformatics applications.

PMID- 22369627
TI  - Characteristics of halorhodopsin-bacterioruberin complex from Natronomonas
      pharaonis membrane in the solubilized system.
AB  - Halorhodopsin is a retinal protein with a seven-transmembrane helix and acts as
      an inward light-driven Cl(-) pump. In this study, structural state of the
      solubilized halorhodopsin (NpHR) from the biomembrane of mutant strain KM-1 of
      Natronomonas pharaonis in nonionic detergent was investigated. A gel filtration
      chromatography monitored absorbances at 280 and 504 nm corresponding to the
      protein and a lipid soluble pigment of bacterioruberin (BR), respectively, has
      clearly detected an oligomer formation of the NpHRs and a complex formation
      between the NpHR and BR in the solubilized system. A molar ratio of NpHR:BR in
      the solubilized complex was close to 1:1. Further SDS-PAGE analysis of the
      solubilized NpHR cross-linked by 1% glutaraldehyde has revealed that the NpHR
      forms homotrimer in detergent system. Although this trimeric structure was stable
      in the presence of NaCl, it was dissociated to the monomer by the heat treatment
      at 45  degrees C in the desalted condition. The same tendency has been reported
      in the case of trimeric NpHR expressed heterologously on the E. coli membrane,
      leading to a conclusion that the change of strength of the trimeric association
      dependent on the ion binding is a universal feature of the NpHR. Interestingly,
      the trimer dissociation on the NpHR was accompanied by the complete dissociation
      of the BR molecule from the protein, indicated that the cavity formed by the NpHR
      protomers in the trimeric conformation is important for tight binding of the BR.
      Because the binding affinity for Cl(-) and the resistance to hydroxylamine under
      light illumination showed only minor differences between the NpHR in the
      solubilized state and that on the biomembrane, the influences of solubilization
      to the tertiary structure and function of the protein are thought to be minor.
      This NpHR-BR complex in the solubilized system has a potential to be a good model
      system to investigate the intermolecular interaction between the membrane protein
      and lipid.

PMID- 22369628
TI  - Enantioselective synthesis of Garner's aldehyde by asymmetric hydroformylation.
AB  - Both enantiomers of Garner's aldehyde (3) are prepared from the same alkene 4 by
      catalytic asymmetric hydroformylation.

PMID- 22369629
TI  - Individualized, transdiagnostic approaches to complex presentations: a case
      study.
AB  - Cognitive behavioural therapy is an evidence-based approach to helping people
      resolve their mental distress. Cognitive behavioural therapy practitioners are
      often encouraged to adapt their interventions according to the person's
      diagnosis. However, this approach can be too simplistic. This paper aimed to
      reflect on working with complex clinical presentations and to explore how
      transdiagnostic approaches can be effectively integrated into standard cognitive
      behavioural interventions. To achieve these aims, a case study of cognitive
      behavioural therapy assessment and treatment was presented. The interventions
      used are described in detail. The move away from a diagnostic-led intervention to
      a transdiagnostic perspective based on the individualized formulation is
      described. Reflections on the process are discussed and the overall approach used
      is evaluated with recommendations made to enhance future clinical practice.

PMID- 22369630
TI  - Unemployment and disability pension--an 18-year follow-up study of a 40-year-old
      population in a Norwegian county.
AB  - BACKGROUND: This study explored the association of unemployment and an increased
      risk of receiving disability pension, and the possibility that this risk is
      attributed to municipality-specific characteristics. METHODS: A cohort of 7,985
      40-42 year olds was followed for 18 years in national registers, identifying new
      episodes of unemployment and cases of disability pension. The association between
      an unemployment period and disability pension in the subsequent year was
      estimated using discrete time multilevel logistic regressions and clustering
      individuals by municipality. The association between unemployment and disability
      pension was adjusted for age in the follow up-period, sex, baseline health
      status, health behaviour and education level. A conditional intra-class
      correlation coefficient (ICC) was estimated as a measure of inter-municipality
      variance. RESULTS: In the follow-up period, 2784 (35%) of the participants were
      granted disability pension. The crude odds ratio for receiving disability pension
      after unemployment (adjusted for age in follow-up period and sex only) was 1.42
      (95% CI 1.1-1.8). Adjusting for baseline health indicators reduced the odds ratio
      of unemployment to 1.33 (CI 1.1-1.7). A fully adjusted model, including education
      level, further reduced the odds ratio of unemployment to 1.25 (CI 1.00-1.6). The
      ICC of the municipality level was approximately 2%. CONCLUSIONS: Becoming
      unemployed increased the risk of receiving subsequent disability pension.
      However, adjusting for baseline health status, health behaviour and education
      attenuated this impact considerably. The multilevel analysis indicated that a
      minor, yet statistically significant, proportion of the risk of disability
      pension can be attributed to the municipality of residence.

PMID- 22369631
TI  - Carers' perspectives of a weight loss intervention for adults with intellectual
      disabilities and obesity: a qualitative study.
AB  - BACKGROUND: To date, no studies have explored the role of carers in supporting
      adults with intellectual disabilities (ID) and obesity during a weight loss
      intervention. The present study explored perceptions of carers supporting adults
      with ID, as they participated in a 6-month multi-component weight loss
      intervention (TAKE 5). METHODS: Semi-structured interviews were used to explore
      the experiences of 24 carers. The transcripts were analysed qualitatively using
      thematic analysis. RESULTS: Three themes emerged from the analysis: carers'
      perceptions of participants' health; barriers and facilitators to weight loss;
      and carers' perceptions of the weight loss intervention. Data analysis showed
      similarities between the experiences reported by the carers who supported
      participants who lost weight and participants who did not. Lack of sufficient
      support from people from the internal and external environment of individuals
      with ID and poor communication among carers, were identified as being barriers to
      change. The need for accessible resources tailored to aid weight loss among
      adults with ID was also highlighted. CONCLUSION: This study identified specific
      facilitators and barriers experienced by carers during the process of supporting
      obese adults with ID to lose weight. Future research could utilise these findings
      to inform appropriate and effective weight management interventions for
      individuals with ID.

PMID- 22369632
TI  - Direct optical carbon dioxide sensing based on a polymeric film doped with a
      selective molecular tweezer-type ionophore.
AB  - A novel optical method for the determination of CO(2) concentration in aqueous
      and gaseous samples of plasticized PVC film is presented. The detection principle
      makes use of a direct molecular recognition of the carbonate ion by a molecular
      tweezer-type ionophore, which has previously been demonstrated to exhibit
      excellent carbonate selectivity. The carbonate ion is extracted together with
      hydrogen ions into a polymeric film that contains the anion exchanger
      tridodecylmethylammonium chloride, a lipophilic, electrically charged, and highly
      basic pH indicator, which is used for the readout in absorbance mode, in addition
      to the lipophilic carbonate ionophore. According to known bulk optode principles,
      such an optical sensor responds to the product of the carbonate ion activity and
      the square of hydrogen ion activity. This quantity is thermodynamically linked to
      the activity of carbon dioxide. This allows one to realize a direct carbon
      dioxide sensor that does not make use of the traditional Severinghaus sensing
      principle of measuring a pH change upon CO(2) equilibration across a membrane. A
      selectivity analysis shows that common ions such as chloride are sufficiently
      suppressed for direct PCO(2) measurements in freshwater samples at pH 8. Chloride
      interference, however, is too severe for direct seawater measurements at the same
      pH. This may be overcome by placing a gas-permeable membrane over the optode
      sensing film. This is conceptually confirmed by establishing that the sensor is
      equally useful for gas-phase PCO(2) measurements. As expected, humid air samples
      are required for proper sensor functioning, as dry CO(2) gas will not cause any
      signal change. The sensor showed acceptable response times and good
      reproducibility under both conditions.

PMID- 22369633
TI  - A singular value decomposition approach for improved taxonomic classification of
      biological sequences.
AB  - BACKGROUND: Singular value decomposition (SVD) is a powerful technique for
      information retrieval; it helps uncover relationships between elements that are
      not prima facie related. SVD was initially developed to reduce the time needed
      for information retrieval and analysis of very large data sets in the complex
      internet environment. Since information retrieval from large-scale genome and
      proteome data sets has a similar level of complexity, SVD-based methods could
      also facilitate data analysis in this research area. RESULTS: We found that SVD
      applied to amino acid sequences demonstrates relationships and provides a basis
      for producing clusters and cladograms, demonstrating evolutionary relatedness of
      species that correlates well with Linnaean taxonomy. The choice of a reasonable
      number of singular values is crucial for SVD-based studies. We found that fewer
      singular values are needed to produce biologically significant clusters when SVD
      is employed. Subsequently, we developed a method to determine the lowest number
      of singular values and fewest clusters needed to guarantee biological
      significance; this system was developed and validated by comparison with Linnaean
      taxonomic classification. CONCLUSIONS: By using SVD, we can reduce uncertainty
      concerning the appropriate rank value necessary to perform accurate information
      retrieval analyses. In tests, clusters that we developed with SVD perfectly
      matched what was expected based on Linnaean taxonomy.

PMID- 22369634
TI  - Linguistic markers of emotion regulation and cardiovascular reactivity among
      older caregiving spouses.
AB  - This study examined linguistic markers of emotion regulation and cardiovascular
      stress reactivity in spousal caregivers. Fifty-three individuals were audiotaped
      while they privately disclosed an instance of partner suffering and a typical
      partner interaction (i.e., a meal together). Systolic blood pressure, diastolic
      blood pressure, and heart rate (HR) were measured. Linguistic analysis determined
      emotion and cognitive processing word use. Results revealed that using more
      positive emotion words was associated with lower HR reactivity in each verbal
      account. Caregivers who used fewer cognitive processing words (e.g., think,
      realize, because) overall had the highest HR reactivity to talking about the
      partner's suffering. These findings have implications for interventions for all
      caregivers as well as distinguishing more resilient caregivers from those who may
      be at a higher risk for caregiver burden.

PMID- 22369635
TI  - Voltammetry of basal plane platinum electrodes in acetonitrile electrolytes:
      effect of the presence of water.
AB  - The first part of this report studies the electrochemical properties of single
      crystal platinum electrodes in acetonitrile electrolytes by means of cyclic
      voltammetry. Potential difference infrared spectroscopy in conjunction with
      linear voltammetry was used to obtain a molecular-level picture of this
      interface. The second part of this report studies the hydrogen evolution and the
      hydrogen oxidation reactions on the three low-index faces of Pt electrodes in
      acetonitrile electrolytes. The data (CVs and IR spectra) strongly suggest that
      acetonitrile and CN(-) molecules are adsorbed on single-crystal platinum
      electrodes in the range of -1.5 to 0.3 V versus Ag/AgCl. Those species block part
      of the adsorption sites for hydrogen adatoms, and they decompose on the surface
      in the presence of water. The nature of the cation and the presence of water
      strongly affect the onset of acetonitrile electrolysis and the kinetics and
      stability of the adsorbed species on the electrode. Finally, the hydrogen
      evolution and the hydrogen oxidation reactions on platinum single-crystal
      surfaces in acetonitrile electrolytes are strongly affected by the surface-energy
      state of Pt electrodes.

PMID- 22369636
TI  - A robust detail preserving anisotropic diffusion for speckle reduction in
      ultrasound images.
AB  - BACKGROUND: Speckles in ultrasound imaging affect image quality and can make the
      post-processing difficult. Speckle reduction technologies have been employed for
      removing speckles for some time. One of the effective speckle reduction
      technologies is anisotropic diffusion. Anisotropic diffusion technology can
      remove the speckles effectively while preserving the edges of the image and thus
      has drawn great attention from image processing scientists. However, the proposed
      methods in the past have different disadvantages, such as being sensitive to the
      number of iterations or low capability of preserving the details of the
      ultrasound images. Thus a detail preserved anisotropic diffusion speckle
      reduction with less sensitive to the number of iterations is needed. This paper
      aims to develop this kind of technologies. RESULTS: In this paper, we propose a
      robust detail preserving anisotropic diffusion filter (RDPAD) for speckle
      reduction. In order to get robust diffusion, the proposed method integrates Tukey
      error norm function into the detail preserving anisotropic diffusion filter
      (DPAD) developed recently. The proposed method could prohibit over-diffusion and
      thus is less sensitive to the number of iterations CONCLUSIONS: The proposed
      anisotropic diffusion can preserve the important structure information of the
      original image while reducing speckles. It is also less sensitive to the number
      of iterations. Experimental results on real ultrasound images show the
      effectiveness of the proposed anisotropic diffusion filter.

PMID- 22369637
TI  - Weight loss, weight regain and bone health.
AB  - The ideal body image for women these days is being slim but, in the real world,
      obesity becomes a major health problem even in the developing countries.
      Overweight, but also underweight, may have associated adverse outcomes in many
      bodily systems, including the bone. Only a few studies have investigated the
      consequences of intentional weight loss, then weight regain, on bone metabolism
      and bone density. It seems that the negative impact of bone loss is not reversed
      when weight partially rebounds following the end of active intervention programs.
      Thus the benefits and risks of any weight loss program should be addressed
      individually, and monitoring of bone parameters is recommended.

PMID- 22369638
TI  - I-domain-antigen conjugate (IDAC) for delivering antigenic peptides to APC:
      synthesis, characterization, and in vivo EAE suppression.
AB  - The objectives of this work are to characterize the identity of I-domain-antigen
      conjugate (IDAC) and to evaluate the in vivo efficacy of IDAC in suppressing
      experimental autoimmune encephalomyelitis (EAE) in mouse model. The hypothesis is
      that the I-domain delivers PLP(139-151) peptides to antigen-presenting cells
      (APC) and alters the immune system by simultaneously binding to ICAM-1 and MHC
      II, blocking immunological synapse formation. IDAC was synthesized by
      derivatizing the lysine residues with maleimide groups followed by conjugation
      with PLP-Cys-OH peptide. Conjugation with PLP peptide does not alter the
      secondary structure of the protein as determined by CD. IDAC suppresses the
      progression of EAE, while I-domain and GMB-I-domain could only delay the onset of
      EAE. As a positive control, Ac-PLP-BPI-NH(2)-2 can effectively suppress the
      progress of EAE. The number of conjugation sites and the sites of conjugations in
      IDAC were determined using tryptic digest followed by LC-MS analysis. In
      conclusion, conjugation of I-domain with an antigenic peptide (PLP) resulted in
      an active molecule to suppress EAE in vivo.

PMID- 22369639
TI  - Assessing the utility of gene co-expression stability in combination with
      correlation in the analysis of protein-protein interaction networks.
AB  - BACKGROUND: Gene co-expression, in the form of a correlation coefficient, has
      been valuable in the analysis, classification and prediction of protein-protein
      interactions. However, it is susceptible to bias from a few samples having a
      large effect on the correlation coefficient. Gene co-expression stability is a
      means of quantifying this bias, with high stability indicating robust, unbiased
      co-expression correlation coefficients. We assess the utility of gene co
      expression stability as an additional measure to support the co-expression
      correlation in the analysis of protein-protein interaction networks. RESULTS: We
      studied the patterns of co-expression correlation and stability in interacting
      proteins with respect to their interaction promiscuity, levels of intrinsic
      disorder, and essentiality or disease-relatedness. Co-expression stability, along
      with co-expression correlation, acts as a better classifier of hub proteins in
      interaction networks, than co-expression correlation alone, enabling the
      identification of a class of hubs that are functionally distinct from the widely
      accepted transient (date) and obligate (party) hubs. Proteins with high levels of
      intrinsic disorder have low co-expression correlation and high stability with
      their interaction partners suggesting their involvement in transient
      interactions, except for a small group that have high co-expression correlation
      and are typically subunits of stable complexes. Similar behavior was seen for
      disease-related and essential genes. Interacting proteins that are both
      disordered have higher co-expression stability than ordered protein pairs. Using
      co-expression correlation and stability, we found that transient interactions are
      more likely to occur between an ordered and a disordered protein while obligate
      interactions primarily occur between proteins that are either both ordered, or
      disordered. CONCLUSIONS: We observe that co-expression stability shows distinct
      patterns in structurally and functionally different groups of proteins and
      interactions. We conclude that it is a useful and important measure to be used in
      concert with gene co-expression correlation for further insights into the
      characteristics of proteins in the context of their interaction network.

PMID- 22369640
TI  - Total synthesis of mevashuntin.
AB  - The total synthesis of (+/-)-mevashuntin, a structurally unique naturally
      occurring pyrano-naphthoquinone-thiazolone, is described. The route is centered
      upon a late stage regioselective Diels-Alder reaction between two highly
      functionalized components, as well as an improved protocol for the one pot
      synthesis of benzothiazolones from ortho-bromoaryl isothiocyanates. The strategy
      results in a highly convergent route, providing access to the natural product in
      11 steps from 3-(4-methoxyphenoxy)propanol and confirming its relative
      stereochemistry.

PMID- 22369641
TI  - The Smc complexes in DNA damage response.
AB  - The structural maintenance of chromosomes (Smc) proteins regulate nearly all
      aspects of chromosome biology and are critical for genomic stability. In
      eukaryotes, six Smc proteins form three heterodimers--Smc1/3, Smc2/4, and Smc5/6-
      which together with non-Smc proteins form cohesin, condensin, and the Smc5/6
      complex, respectively. Cohesin is required for proper chromosome segregation. It
      establishes and maintains sister-chromatid cohesion until all sister chromatids
      achieve bipolar attachment to the mitotic spindle. Condensin mediates chromosome
      condensation during mitosis. The Smc5/6 complex has multiple roles in DNA repair.
      In addition to their major functions in chromosome cohesion and condensation,
      cohesin and condensin also participate in the cellular DNA damage response. Here
      we review recent progress on the functions of all three Smc complexes in DNA
      repair and their cell cycle regulation by posttranslational modifications, such
      as acetylation, phosphorylation, and sumoylation. An in-depth understanding of
      the mechanisms by which these complexes promote DNA repair and genomic stability
      may help us to uncover the molecular basis of genomic instability in human
      cancers and devise ways that exploit this instability to treat cancers.

PMID- 22369642
TI  - Compliance with dietary guidelines in grocery purchasing among older adults by
      chewing ability and socio-economic status.
AB  - BACKGROUND: Dietary guidelines promote good nutrition through healthy eating.
      Chewing deficiencies may hinder food intake while lower socio-economic status
      (SES) may restrict food purchasing. The aim was to examine compliance of grocery
      purchasing behaviour with dietary guidelines by chewing ability and SES. METHODS:
      Adults aged 60-71 years in Adelaide, South Australia were surveyed in 2008.
      Dietary guideline compliance was measured using 16 grocery purchasing items.
      Chewing ability was based on a 5-item Chewing Index. SES was assessed using a
      subjective social status rating representing where people stand in society.
      RESULTS: Responses were collected from n = 444 persons (response rate = 68.8%).
      Among dentate persons, 10.3% were chewing deficient and 21.3% were in the lower
      SES group. Prevalence ratios (PR: 95% CI) controlling for SES showed chewing
      deficiency was related to (p < 0.05) non-compliance with dietary guidelines in
      relation to bread (1.7: 1.1-2.5), juice (2.7: 1.6-4.5), tinned fruit (2.9: 1.5
      5.6), yoghurt (2.1: 1.2-3.7) and tinned fish (1.5: 1.2-1.9). CONCLUSIONS: Chewing
      deficiency was associated with lower compliance with dietary guidelines in
      relation to fibre, sugar, fat and salt. Chewing deficiency may have a direct
      effect on diet as well as reflect a clustering of risk in relation to a range of
      health behaviours.

PMID- 22369643
TI  - Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to
      disrupt the VHL/HIF-1alpha interaction.
AB  - E3 ubiquitin ligases, which bind protein targets, leading to their ubiquitination
      and subsequent degradation, are attractive drug targets due to their exquisite
      substrate specificity. However, the development of small-molecule inhibitors has
      proven extraordinarily challenging as modulation of E3 ligase activities requires
      the targeting of protein-protein interactions. Using rational design, we have
      generated the first small molecule targeting the von Hippel-Lindau protein (VHL),
      the substrate recognition subunit of an E3 ligase, and an important target in
      cancer, chronic anemia, and ischemia. We have also obtained the crystal structure
      of VHL bound to our most potent inhibitor, confirming that the compound mimics
      the binding mode of the transcription factor HIF-1alpha, a substrate of VHL.
      These results have the potential to guide future development of improved lead
      compounds as therapeutics for the treatment of chronic anemia and ischemia.

PMID- 22369644
TI  - Ethyl pyruvate induces heme oxygenase-1 through p38 mitogen-activated protein
      kinase activation by depletion of glutathione in RAW 264.7 cells and improves
      survival in septic animals.
AB  - AIMS: We investigated the molecular mechanism by which ethyl pyruvate (EP)
      induces heme oxygenase-1 (HO-1) in RAW 264.7 cells and its effect on survival
      rate in cecal ligation and puncture (CLP)-induced wild-type (WT) and HO-1
      knockout (HO-1(-/-)) septic mice. RESULTS: EP induced HO-1 in a dose- and time
      dependent manner, which was mediated through p38 mitogen-activated protein kinase
      (MAPK) and NF-E2-related factor 2 (Nrf2) signaling cascade in RAW 264.7 cells. EP
      significantly inhibited the lipopolysaccharide (LPS)-stimulated inducible nitric
      oxide synthase (iNOS) expression and high-mobility group box 1 (HMGB1) release in
      RAW 264.7 cells. The inhibitory effect of EP on LPS-stimulated iNOS expression
      and HMGB1 release was reversed by transfection with siHO-1RNA in RAW 264.7 cells,
      but EP failed to reduce them in HO-1(-/-) peritoneal macrophages treated with
      LPS. Moreover, treatment of cells with glutathione ethyl ester (GSH-Et), SB203580
      (p38 MAPK inhibitor), siHO-1, or p38-siRNA transfection inhibited anti
      inflammatory effect of EP. Interestingly, both HO-1 induction and phosphorylation
      of p38 by EP were reversed by GSH-Et, and antioxidant redox element-luciferase
      activity by EP was reversed by SB203580 in LPS-activated cells. EP increased
      survival and decreased serum HMGB1 in CLP-WT mice, whereas it did not increase
      survival or decrease circulating HMGB1 in HO-1(-/-) CLP-mice. INNOVATION AND
      CONCLUSION: Our work provides new insights into the understanding the molecular
      mechanism by showing that EP induces HO-1 through a p38 MAPK- and NRF2-dependent
      pathway by decreasing GSH cellular levels. We conclude that EP inhibits
      proinflammatory response to LPS in macrophages and increases survival in CLP
      induced septic mice by upregulation of HO-1 level, in which p38 MAPK and Nrf2
      play an important role.

PMID- 22369645
TI  - Salamanders and fish can regenerate lost structures--why can't we?
AB  - The recent introduction of in vivo lineage-tracing techniques using
      fluorescently labeled cells challenged the long-standing view that complete
      dedifferentiation is a major force driving vertebrate tissue regeneration. The
      report in BMC Developmental Biology by Juan Carlos Izpisua Belmonte and
      colleagues adds a new twist to a rapidly evolving view of the origin of blastemal
      cells. As classic and recent experimental findings are considered together, a new
      perspective on vertebrate muscle regeneration is emerging.See research article
      http://www.biomedcentral.com/1471-213X/12/9.

PMID- 22369646
TI  - Soybean Knowledge Base (SoyKB): a web resource for soybean translational
      genomics.
AB  - BACKGROUND: Soybean Knowledge Base (SoyKB) is a comprehensive all-inclusive web
      resource for soybean translational genomics. SoyKB is designed to handle the
      management and integration of soybean genomics, transcriptomics, proteomics and
      metabolomics data along with annotation of gene function and biological pathway.
      It contains information on four entities, namely genes, microRNAs, metabolites
      and single nucleotide polymorphisms (SNPs). METHODS: SoyKB has many useful tools
      such as Affymetrix probe ID search, gene family search, multiple gene/metabolite
      search supporting co-expression analysis, and protein 3D structure viewer as well
      as download and upload capacity for experimental data and annotations. It has
      four tiers of registration, which control different levels of access to public
      and private data. It allows users of certain levels to share their expertise by
      adding comments to the data. It has a user-friendly web interface together with
      genome browser and pathway viewer, which display data in an intuitive manner to
      the soybean researchers, producers and consumers. CONCLUSIONS: SoyKB addresses
      the increasing need of the soybean research community to have a one-stop-shop
      functional and translational omics web resource for information retrieval and
      analysis in a user-friendly way. SoyKB can be publicly accessed at
      http://soykb.org/.

PMID- 22369647
TI  - Determination of benzo[a]pyrene-7,10-quinone in airborne particulates by using a
      chemiluminescence reaction of hydrogen peroxide and hydrosulfite.
AB  - An ultraweak chemiluminescence (CL) was observed when sodium hydrosulfite
      (NaHSO(3)) reacts with hydrogen peroxide (H(2)O(2)) and was enhanced 70 times by
      adding 10 pmol benzo[a]pyrene-7,10-quinone (7,10-BaPQ). The CL reaction is fast,
      and it reached maximum intensity in 0.1 s, and then decayed to baseline in 3 s.
      Mechanism of NaHSO(3)-7,10-BaPQ-H(2)O(2) system were investigated by CL spectrum,
      radical scavengers and electron spin resonance (ESR). Hydroxyl radical ((*)OH),
      super oxide anion radical ((*)O(2)(-)), and sulfite radical ((*)SO(3)(-)) were
      generated in the NaHSO(3)-7, 10-BaPQ-H(2)O(2) system. Reduction of 7,10-BaPQ by
      (*)O(2)(-) radical gave excited semiquinone, which showed strong CL emission when
      decayed to its ground state. Maximum CL emission wavelength was located at 440
      nm, which may belong to the excited semiquinone. This CL system was developed as
      post column detection of high performance liquid chromatography for the
      determination of 7,10-BaPQ. Linearity ranged from 50 fmol to 20 pmol (R(2) =
      0.9995) with limit of detection of 30 fmol (S/N = 3). The proposed method was
      used to determine 7,10-BaPQ in airborne particulates. Average atmospheric
      concentrations of 7,10-BaPQ in Kanazawa in December 2010 and Wajima in October
      2007 were 2.0 and 1.6 pg/m(3), respectively.

PMID- 22369648
TI  - Enzymatic characteristics of crude feruloyl and acetyl esterases of rumen fungus
      Neocallimastix sp. YAK11 isolated from yak (Bos grunniens).
AB  - Rumen fungus Neocallimastix sp. YAK11 was isolated from yak (Bos grunniens), and
      three consecutive 10-day pure cultures were anaerobically performed at 39 
      degrees C in 20-ml Hungate's tubes to explore ferulic acid esterase (FAE) and
      acetyl esterase (AE) activity profiles of the fungus grown on whole hay fraction
      of Chinese wildrye grass (Leymus chinensis) (WHOcw , n = 4) and its neutral
      detergent fibre fraction (NDFcw , n = 4), respectively. An aliquot of 0.7-ml
      culture was sampled daily using a sterile syringe, and 0.7-ml fresh medium was
      immediately added to the tubes to compensate for the withdrawn samples. Peak
      esterase activity occurred for FAE on day 5 (p < 0.001) and for AE on day 6 (p <
      0.001). The mean activities of FAE and AE in WHOcw were 2.07 and 1.29 times of
      those in NDFcw (p < 0.001). Both FAE and AE activities were positively correlated
      with xylanase (r > 0.65, p < 0.001) and carboxymethyl cellulase (r > 0.57, p <
      0.001) activities. Total volatile fatty acid concentration was positively
      correlated with enzyme activities of AE (r > 0.87, p < 0.001), FAE (r > 0.82, p <
      0.001) and xylanase (r > 0.56, p < 0.001). Crude enzyme solution was harvested
      for the fungus grown on WHOcw , and the pH optimum of FAE activity was 8.0 while
      the optimum for AE was 9.0. Both FAE and AE had a broad pH stability range. The
      optimal temperatures for FAE and AE activity were 40 and 50  degrees C. The
      Michaelis constant (Km ) and maximum velocity (Vmax ) for FAE against methyl
      ferulate at pH 6.0 and 39  degrees C were 0.078 mm and 2.93 mU, respectively. The
      Km and Vmax for AE against p-nitrophenyl acetate at pH 7.0 and 39  degrees C were
      2.73 mm and 666.67 mU, respectively. Both FAE and AE may have prospective
      advantages for the enzymatic degradation of roughages in ruminant animals.

PMID- 22369649
TI  - Measuring social anxiety in college students: a comprehensive evaluation of the
      psychometric properties of the SPAI-23.
AB  - Social anxiety disorder (SAD) is 1 of the most prevalent psychological disorders,
      and among college students in particular, social anxiety has been associated with
      other problems such as substance use problems and increased vulnerability to
      other psychiatric disorders. The Social Phobia and Anxiety Inventory-23 (SPAI-23;
      Roberson-Nay, Strong, Nay, Beidel, & Turner, 2007) may be a useful, brief measure
      of problematic social anxiety in college students. Results from 4 studies (total
      n = 2,436) using the SPAI-23 with college student samples are presented. Scores
      on the SPAI-23 demonstrated strong convergent validity with other measures of
      social anxiety and discriminant validity as evidenced by lower correlations with
      measures of dissimilar constructs. Difference scores on the SPAI-23 also
      demonstrated adequate test-retest reliability over 5 1/2 weeks (r = .72).
      Exploratory factor analysis suggested a two-factor structure: social anxiety and
      agoraphobia. Finally, differential item function analyses suggested that the
      items function similarly in men and women. In conclusion, the SPAI-23
      demonstrated strong psychometric properties for use with college students.

PMID- 22369650
TI  - Measuring beliefs about suffering: development of the views of suffering scale.
AB  - Efforts to measure religion have intensified, and many specific dimensions have
      been identified. However, although belief is a core dimension of all world
      religions, little attention has been given to assessment of religious beliefs. In
      particular, 1 essential set of religious beliefs, those concerning the reasons
      for human suffering, has remained virtually unexamined despite the potential
      clinical relevance of these beliefs. To fill the need for a measure of people's
      beliefs about suffering, we developed the Views of Suffering Scale (VOSS).
      Analyses identified factors related to traditional Christian teachings,
      unorthodox theistic beliefs, karma, and randomness. Internal consistency and test
      retest reliability for VOSS subscale scores were good (alphas and rs >= .70).
      Comparisons to measures of related constructs suggest that the VOSS scores
      demonstrate good convergent validity. One subscale score was modestly correlated
      with social desirability related to image management, and 7 were positively
      correlated to self-deceptive enhancement. These preliminary studies suggest that
      the VOSS differentiates religious perspectives on suffering among a sample of
      U.S. university students, though more research is needed to confirm its utility
      in diverse populations. The VOSS provides a valid way to measure individuals'
      beliefs about suffering, allowing for inquiry into the factors that lead to
      various beliefs about suffering and the roles of these beliefs in adjusting to
      stressful life events.

PMID- 22369651
TI  - Assessing guilt toward the former spouse.
AB  - Divorce is often accompanied by feelings of guilt toward the former spouse. So
      far, no scale has been available to measure such feelings. For this purpose, the
      authors developed the Guilt in Separation Scale (GiSS). Content validity was
      assured by using experts and lay experts to generate and select items.
      Exploratory analyses were run on samples of 214 divorced individuals and
      confirmatory analyses on 458 individuals who were in the process of divorcing.
      Evidence was provided for the reliability and construct validity of the GiSS. The
      internal consistency was high (alpha = .91), as were the 6-month and 12-month
      test-retest reliabilities (r = .72 and r = .76, respectively). The GiSS was
      related to shame, regret, compassion, locus of cause of the separation,
      unfaithfulness, and psychological functioning.

PMID- 22369652
TI  - Concepts of social inclusion, exclusion and mental health: a review of the
      international literature.
AB  - Social inclusion and exclusion are concepts which have been widely associated
      with politics and policy in the first decade of the 2000s. People with mental
      health problems have become the focus of a range of social inclusion initiatives.
      A literature review was conducted to explore the peer-reviewed evidence relating
      social inclusion/exclusion and mental health. In total 36 papers were included in
      the review from the UK, Canada, Australia and Scandinavia. The papers had used a
      range of different approaches to research and evaluation. The included papers
      associated being socially included to: social roles and responsibilities such as
      employment, participation in social activities, environmental work and voting.
      Although some papers engaged in a critical discussion of the concept, many
      offered only simplistic accounts or definitions. Social inclusion is such a
      widely used term within political and policy discourses that it is surprising so
      little research is available within the mental health realm. There was a lack of
      clarity related to the concept of social exclusion and the qualitative studies
      focused entirely on the experiences of being excluded within an institutional or
      semi-institutional setting. The relationship between exclusion, inequality and
      injustice is identified and the relevance of the concept to current and future
      mental health policy is questioned.

PMID- 22369654
TI  - Asymmetric Michael addition of alpha-substituted isocyanoacetates with maleimides
      catalyzed by chiral tertiary amine thiourea.
AB  - A highly diastereoselective and enantioselective Michael addition of alpha
      substituted isocyanoacetates with maleimides catalyzed by bifunctional tertiary
      amine thioureas has been developed. Various chiral succinimide derivatives
      bearing adjacent quaternary and tertiary stereocenters were prepared in excellent
      yields (up to 98%), diastereoselectivities (up to 99:1), and enantioselectivities
      (up to 98% ee). The synthetic utility of chiral succinimide derivatives is also
      demonstrated in the preparation of h5-HT(1d) receptor agonist motifs.

PMID- 22369653
TI  - The effectiveness of land based exercise compared to decompressive surgery in the
      management of lumbar spinal-canal stenosis: a systematic review.
AB  - BACKGROUND: Lumbar spinal stenosis (LSS) is prevalent in those over the age of 65
      years and the leading cause of spinal surgery in this population. Recent
      systematic reviews have examined the effectiveness of conservative management for
      LSS, but not relative to surgical interventions. The aim of this review was to
      systematically examine the effectiveness of land based exercise compared with
      decompressive surgery in the management of patients with LSS. METHODS: A
      systematic review of randomised controlled trials and clinical trials was
      undertaken. The databases MEDLINE, Embase, CINAHL, PEDro and Cochrane Library
      Register of Controlled Trials were searched from January 2000 to June 2011. Only
      studies that included subjects with lumbar spinal canal stenosis were considered
      in this review. Studies also had to use a patient reported functional outcome
      measure for a land based exercise intervention or lumbar decompressive surgery.
      RESULTS: Only one study compared the effectiveness of exercise and decompressive
      surgery for LSS. Surgery demonstrated statistically significant improvements in
      patient reported functional outcome scores at 6, 12 and 24-months post
      intervention (p < 0.01). To facilitate further analysis, the results from 12
      exercise and 10 surgical intervention arms were compared using percentage change
      in patient reported functional outcome measure scores. Exercise interventions
      showed initial improvements, ranging from 16 to 29% above baseline. All
      decompressive surgical interventions demonstrated greater and sustained
      improvements over 2-years (range 38-67% improvement) with moderate to large
      effect sizes. The most commonly reported complications associated with surgery
      were dural tears, while details of adverse effects were lacking in exercise
      interventions. CONCLUSIONS: This systematic review of the recent literature
      demonstrates that decompressive surgery is more effective than land based
      exercise in the management of LSS. However, given the condition's slowly
      progressive nature and the potential for known surgical complications, it is
      recommended that a trial of conservative management with land based exercise be
      considered prior to consideration of surgical intervention.

PMID- 22369655
TI  - Psychometric evaluation of a scale to assess satisfaction with life among people
      with intellectual disabilities living in community residences.
AB  - BACKGROUND: In the context of a health intervention among people with
      intellectual disabilities (ID), there was a need to assess satisfaction with some
      aspects of life, in order to monitor both potential positive and negative effects
      of the intervention. The aim of the present study was to develop and evaluate an
      easily administered scale for assessing satisfaction with home environment and
      leisure time among people with mild or moderate ID, living in community
      residences. METHODS: A number of questions were constructed to measure
      satisfaction with home environment and leisure time. The questions were answered
      by 132 adults with mild or moderate ID, living in community residences in Sweden.
      The dimensionality of the scale was evaluated by factor analysis, and the
      reliability was estimated using Cronbach's alpha coefficients. RESULTS: The
      analysis supported a four-factor solution with 12 items. The four factors were:
      (I) Satisfaction with housing environment; (II) Satisfaction with life; (III)
      Satisfaction with meals; and (IV) Satisfaction with recreational activity. The
      four factors explained almost 70% of the variance in the data set. Cronbach alpha
      coefficients for all scales were above 0.70, indicating that the reliabilities of
      the scales were satisfactory. Correlations between the four sub-scales ranged
      from 0.06 to 0.52, indicating low to moderate inter-correlations between the four
      sub-scales. CONCLUSION: The scale has fairly good psychometric properties and is
      easy to administer. The scale, which can be further improved, can be an important
      resource in health intervention studies.

PMID- 22369657
TI  - Surfactant-induced Marangoni eddies alter the coffee-rings of evaporating
      colloidal drops.
AB  - The influence of the small ionic surfactant sodium dodecyl sulfate (SDS) on the
      evaporation of drying colloidal droplets is quantitatively investigated. The
      addition of SDS leads to a significantly more uniform deposition of colloidal
      particles after evaporation (i.e., the so-called "coffee-ring effect" is
      dramatically altered). We understand this phenomenon in the context of
      circulating radial Marangoni flows induced by the variation of SDS concentration
      along the air-water interface. Video microscopy permits the direct visualization
      of the colloidal particles involved in these flows, revealing a surprisingly
      stable "Marangoni eddy" that prevents particle deposition at the drop perimeter.

PMID- 22369656
TI  - Functional complementation between transcriptional methylation regulation and
      post-transcriptional microRNA regulation in the human genome.
AB  - BACKGROUND: DNA methylation in the 5' promoter regions of genes and microRNA
      (miRNA) regulation at the 3' untranslated regions (UTRs) are two major epigenetic
      regulation mechanisms in most eukaryotes. Both DNA methylation and miRNA
      regulation can suppress gene expression and their corresponding protein product;
      thus, they play critical roles in cellular processes. Although there have been
      numerous investigations of gene regulation by methylation changes and miRNAs,
      there is no systematic genome-wide examination of their coordinated effects in
      any organism. RESULTS: In this study, we investigated the relationship between
      promoter methylation at the transcription level and miRNA regulation at the post
      transcription level by taking advantage of recently released human methylome data
      and high quality miRNA and other gene annotation data. We found methylation level
      in the promoter regions and expression level was negatively correlated. Then, we
      showed that miRNAs tended to target the genes with a low DNA methylation level in
      their promoter regions. We further demonstrated that this observed pattern was
      not attributed to the gene expression level, expression broadness, or the number
      of transcription factor binding sites. Interestingly, we found miRNA target sites
      were significantly enriched in the genes located in differentially methylated
      regions or partially methylated domains. Finally, we explored the features of DNA
      methylation and miRNA regulation in cancer genes and found cancer genes tended to
      have low methylation level and more miRNA target sites. CONCLUSION: This is the
      first genome-wide investigation of the combined regulation of gene expression.
      Our results supported a complementary regulation between DNA methylation
      (transcriptional level) and miRNA function (post-transcriptional level) in the
      human genome. The results were helpful for our understanding of the evolutionary
      forces towards organisms' complexity beyond traditional sequence level
      investigation.

PMID- 22369658
TI  - DetoxiProt: an integrated database for detoxification proteins.
AB  - BACKGROUND: Detoxification proteins are a class of proteins for degradation
      and/or elimination of endogenous and exogenous toxins or medicines, as well as
      reactive oxygen species (ROS) produced by these materials. Most of these proteins
      are generated as a response to the stimulation of toxins or medicines. They are
      essential for the clearance of harmful substances and for maintenance of
      physiological balance in organisms. Thus, it is important to collect and
      integrate information on detoxification proteins. RESULTS: To store, retrieve and
      analyze the information related to their features and functions, we developed the
      DetoxiProt, a comprehensive database for annotation of these proteins. This
      database provides detailed introductions about different classes of the
      detoxification proteins. Extensive annotations of these proteins, including
      sequences, structures, features, inducers, inhibitors, substrates, chromosomal
      location, functional domains as well as physiological-biochemical properties were
      generated. Furthermore, pre-computed BLAST results, multiple sequence alignments
      and evolutionary trees for detoxification proteins are also provided for
      evolutionary study of conserved function and pathways. The current version of
      DetoxiProt contains 5956 protein entries distributed in 628 organisms. An easy to
      use web interface was designed, so that annotations about each detoxification
      protein can be retrieved by browsing with a specific method or by searching with
      different criteria. CONCLUSIONS: DetoxiProt provides an effective and efficient
      way of accessing the detoxification protein sequences and other high-quality
      information. This database would be a valuable source for toxicologists,
      pharmacologists and medicinal chemists. DetoxiProt database is freely available
      at http://lifecenter.sgst.cn/detoxiprot/.

PMID- 22369659
TI  - In vivo and in vitro evaluation of the therapeutic potential of some Turkish
      Scorzonera species as wound healing agent.
AB  - Wound healing and anti-inflammatory effects of aerial parts and roots of S.
      acuminata, S. cana var. alpina, S. cana var. jacquiniana, S. cana var. radicosa,
      S. eriophora, S. laciniata ssp. laciniata, S. suberosa ssp. suberosa and S.
      sublanata were investigated in current study to clarify the traditional usage of
      Scorzonera species growing in Turkey. It is well known that some species of the
      Scorzonera genus are used for wound healing in Turkish and European traditional
      medicine. Therefore, wound healing effect of the plants was assessed by using
      linear incision and circular excision experimental wound models and subsequently
      histopathological analysis. Hydroxyproline content of the treated tissues was
      also assessed. Furthermore, the extracts were screened for anti-hyaluronidase
      activity. For the evaluation of anti-inflammatory activity, acetic acid-induced
      increase in capillary permeability test was used. 20% aqueous methanol extracts
      of the aerial parts of Scorzonera species, S. cana var. jacquiniana and S.
      eriophora were found to be effective on the wound and anti-inflammatory activity
      test models. The results of histopathological examination supported the outcome
      of linear incision and circular excision wound models. Phytochemical analyses of
      the tested extracts were also performed by using developed and validated HPLC
      method. Among the tested standard compounds, varying amounts of the chlorogenic
      acid, rutin, hyperoside and luteolin-7-glycoside were determined in Scorzonera
      species.

PMID- 22369662
TI  - The oral health-related quality of life in edentulous patients treated with
      conventional complete dentures.
AB  - OBJECTIVE: To compare the oral health-related quality of life (OHRQoL) between
      patients with both maxillary and mandibular complete denture and those with
      either the maxillary or the mandibular complete denture. BACKGROUND: Satisfaction
      of denture wearers can be estimated using the OHRQoL questionnaires like the OHIP
      EDENT and the Geriatric Oral Health Assessment Index (GOHAI). METHODS: Two
      questionnaires were used to compare the OHRQoL between edentulous patients who
      had conventional removable complete denture on both jaws and those who had on
      either one of the jaws. RESULT: The age of the participants ranged from 42 to 75
      years, with the mean age of 58 +/- 8.12 years. The mean OHIP-EDENT scores were
      significantly high among those who wore conventional dentures in both jaws (54.12
      +/- 5.21), compared with the participants who only had denture either on upper or
      lower jaw (46.52 +/- 7.35). It was noticed that the mean GOHAI score was
      significantly lower (p < 0.05) among participants who had conventional denture on
      both upper and lower jaw (28.25 +/- 3.67), as compared to those who had
      conventional denture only on one arch (35.12 +/- 2.11). CONCLUSION: Patients with
      complete dentures in both jaw (Group I) were less satisfied than patients with
      single complete denture (Group II). The result obtained in this study shows
      dissatisfaction with conventional dentures among edentulous patients.

PMID- 22369660
TI  - BRCA1 tumor suppressor network: focusing on its tail.
AB  - Germline mutations of the BRCA1 tumor suppressor gene are a major cause of
      familial breast and ovarian cancer. BRCA1 plays critical roles in the DNA damage
      response that regulates activities of multiple repair and checkpoint pathways for
      maintaining genome stability. The BRCT domains of BRCA1 constitute a phospho
      peptide binding domain recognizing a phospho-SPxF motif (S, serine; P, proline; *
      varies; F, phenylalanine). The BRCT domains are frequently targeted by clinically
      important mutations and most of these mutations disrupt the binding surface of
      the BRCT domains to phosphorylated peptides. The BRCT domain and its capability
      to bind phosphorylated protein is required for the tumor suppressor function of
      BRCA1. Through its BRCT phospho-binding ability BRCA1 forms at least three
      mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1
      and CTIP. The A, B and C complexes, at lease partially undertake BRCA1's role in
      mechanisms of cell cycle checkpoint and DNA repair that maintain genome
      stability, thus may play important roles in BRCA1's tumor suppressor function.

PMID- 22369663
TI  - Global analysis of phosphoproteome regulation by the Ser/Thr phosphatase Ppt1 in
      Saccharomyces cerevisiae.
AB  - Even though protein phosphatases are key regulators of signal transduction, their
      cellular mechanisms of action are poorly understood. Here, we undertook a large
      scale proteomics survey to identify cellular protein targets of a
      serine/threonine phosphatase. We used SILAC-based quantitative MS to measure
      differences in protein expression and phosphorylation upon ablation of the
      serine/threonine phosphatase Ppt1 in Saccharomyces cerevisiae. Phosphopeptide
      fractionation by strong cation exchange chromatography combined with immobilized
      metal affinity chromatography (IMAC) enrichment enabled quantification of more
      than 8000 distinct phosphorylation sites in Ppt1 wild-type versus Ppt1-deficient
      yeast cells. We further quantified the relative expression of 1897 yeast proteins
      and detected no major protein changes accompanying Ppt1 deficiency. Notably, we
      found 33 phosphorylation sites to be significantly and reproducibly up-regulated
      while no phosphorylation events were repressed in cells lacking Ppt1. Ppt1 acted
      on its cellular target proteins in a sequence- and site-specific fashion. Several
      of the regulated phosphoproteins were involved in the response to heat stress in
      agreement with known Ppt1 functions. Additionally, biosynthetic enzymes were
      particularly prominent among Ppt1-regulated phosphoproteins, pointing to
      unappreciated roles of Ppt1 in the control of various metabolic functions. These
      results demonstrate the utility of large-scale and quantitative phosphoproteomics
      to identify cellular sites of serine/threonine phosphatase action in an unbiased
      manner.

PMID- 22369664
TI  - Engineered polymer-supported synthesis of 3'-carboxyalkyl-modified
      oligonucleotides and their applications in the construction of biochips for
      diagnosis of the diseases.
AB  - An engineered polymer support 5 has been prepared for the solid-phase assembly of
      3'-carboxyalkyl-modified oligonucleotides using commonly available reagents. A
      two-step deprotection procedure resulted in the quantitative cleavage of
      oligonucleotides from the support and removal of the protecting groups from
      phosphodiesters and exocyclic amino groups of the nucleic bases. The fully
      deprotected oligomers, obtained in high yield, were desalted and analyzed on RP
      HPLC. After characterization by MALDI-TOF, these carboxyalkylated
      oligonucleotides were immobilized onto the epoxy-functionalized glass microslides
      to prepare biochips. The performance of these biochips was evaluated under
      different sets of conditions and then successfully validated by the detection of
      base mismatches and human infectious disease, bacterial meningitis, caused by N.
      meningitidis.

PMID- 22369665
TI  - Cutoff Scanning Matrix (CSM): structural classification and function prediction
      by protein inter-residue distance patterns.
AB  - BACKGROUND: The unforgiving pace of growth of available biological data has
      increased the demand for efficient and scalable paradigms, models and
      methodologies for automatic annotation. In this paper, we present a novel
      structure-based protein function prediction and structural classification method:
      Cutoff Scanning Matrix (CSM). CSM generates feature vectors that represent
      distance patterns between protein residues. These feature vectors are then used
      as evidence for classification. Singular value decomposition is used as a
      preprocessing step to reduce dimensionality and noise. The aspect of protein
      function considered in the present work is enzyme activity. A series of
      experiments was performed on datasets based on Enzyme Commission (EC) numbers and
      mechanistically different enzyme superfamilies as well as other datasets derived
      from SCOP release 1.75. RESULTS: CSM was able to achieve a precision of up to 99%
      after SVD preprocessing for a database derived from manually curated protein
      superfamilies and up to 95% for a dataset of the 950 most-populated EC numbers.
      Moreover, we conducted experiments to verify our ability to assign SCOP class,
      superfamily, family and fold to protein domains. An experiment using the whole
      set of domains found in last SCOP version yielded high levels of precision and
      recall (up to 95%). Finally, we compared our structural classification results
      with those in the literature to place this work into context. Our method was
      capable of significantly improving the recall of a previous study while
      preserving a compatible precision level. CONCLUSIONS: We showed that the patterns
      derived from CSMs could effectively be used to predict protein function and thus
      help with automatic function annotation. We also demonstrated that our method is
      effective in structural classification tasks. These facts reinforce the idea that
      the pattern of inter-residue distances is an important component of family
      structural signatures. Furthermore, singular value decomposition provided a
      consistent increase in precision and recall, which makes it an important
      preprocessing step when dealing with noisy data.

PMID- 22369666
TI  - Detection of interacting transcription factors in human tissues using predicted
      DNA binding affinity.
AB  - BACKGROUND: Tissue-specific gene expression is generally regulated by
      combinatorial interactions among transcription factors (TFs) which bind to the
      DNA. Despite this known fact, previous discoveries of the mechanism that controls
      gene expression usually consider only a single TF. RESULTS: We provide a
      prediction of interacting TFs in 22 human tissues based on their DNA-binding
      affinity in promoter regions. We analyze all possible pairs of 130 vertebrate TFs
      from the JASPAR database. First, all human promoter regions are scanned for
      single TF-DNA binding affinities with TRAP and for each TF a ranked list of all
      promoters ordered by the binding affinity is created. We then study the
      similarity of the ranked lists and detect candidates for TF-TF interaction by
      applying a partial independence test for multiway contingency tables. Our
      candidates are validated by both known protein-protein interactions (PPIs) and
      known gene regulation mechanisms in the selected tissue. We find that the known
      PPIs are significantly enriched in the groups of our predicted TF-TF interactions
      (2 and 7 times more common than expected by chance). In addition, the predicted
      interacting TFs for studied tissues (liver, muscle, hematopoietic stem cell) are
      supported in literature to be active regulators or to be expressed in the
      corresponding tissue. CONCLUSIONS: The findings from this study indicate that
      tissue-specific gene expression is regulated by one or two central regulators and
      a large number of TFs interacting with these central hubs. Our results are in
      agreement with recent experimental studies.

PMID- 22369667
TI  - Transcriptome changes in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a debilitating, common cause of visual
      impairment. While the last decade has seen great progress in understanding the
      pathophysiology of AMD, the molecular changes that occur in eyes with AMD are
      still poorly understood. In the current issue of Genome Medicine, Newman and
      colleagues present the first systematic transcriptional profile analysis of AMD
      affected tissues, providing a comprehensive set of expression data for different
      regions (macula versus periphery), tissues (retina versus retinal pigment
      epithelium (RPE)/choroid), and disease state (control versus early or advanced
      AMD). Their findings will serve as a foundation for additional systems-level
      research into the pathogenesis of this blinding disease.

PMID- 22369668
TI  - Evaluating psychological markers for human nicotine dependence: tobacco choice,
      extinction, and Pavlovian-to-instrumental transfer.
AB  - Individual differences in drug dependence may be mediated by several
      abnormalities in associative learning, including perseveration of drug-seeking
      following contingency change, greater control over drug-seeking by Pavlovian
      stimuli, or greater sensitivity to drug reinforcement establishing higher rates
      of drug-seeking. To evaluate these three candidate markers for nicotine
      dependence, Experiment 1 contrasted daily (N = 22) and nondaily smoker groups (N
      = 22) on a novel instrumental learning task, where one S+ was first trained as a
      predictor of tobacco reward before being extinguished. Experiment 2 compared
      daily (N = 18) and nondaily smoker groups (N = 18) on a concurrent-choice task
      for tobacco and chocolate reward before an extinction test in which the tobacco
      response was extinguished, followed by a Pavlovian-to-instrumental transfer test,
      wherein the impact of tobacco and chocolate cues on concurrent choice was
      measured (gender was balanced within each smoker group). The results showed no
      group difference in sensitivity to extinction of either the stimulus-drug or
      response-drug contingency in Experiments 1 and 2, respectively, nor did groups
      show a difference in Pavlovian-to-instrumental transfer of control over tobacco
      choice. By contrast, nicotine-dependence status was marked by a higher frequency
      of tobacco choice in the concurrent-choice procedure, and this choice preference
      was associated with subjective craving (gender did not affect any behavioral
      measure). These results favor the view that nicotine dependence in this sample is
      not determined by individual predilection for perseveration or stimulus-control
      over drug-seeking, but by greater sensitivity to reinforcement of instrumental
      drug choice. Value-based decision theories of dependence are discussed.

PMID- 22369669
TI  - Sex differences in the cognitive effects of tobacco abstinence: a pilot study.
AB  - Despite significant research demonstrating the deleterious effects of tobacco
      abstinence on memory, and research showing substantial sex differences in
      nicotine withdrawal and memory processes, there has been scant work on how males
      and females might differ in the effects of tobacco abstinence on memory and
      cognition. Using a standard recognition memory task, we conducted a pilot study
      to examine how 24 hours of tobacco abstinence in moderate to heavy smokers would
      affect memory in males and females. Twenty-five moderate to heavy smokers were
      tested following a period of smoking normally and following 24 hours of tobacco
      abstinence. At each session, participants completed a recognition memory task in
      which items were studied under full- and divided-attention conditions (a standard
      manipulation of memory encoding) as well as tests of passive short-term and
      working memory (forward and backward digit span). Tobacco abstinence
      significantly reduced memory performance under full attention conditions for
      males but not for females. A significant main effect of smoking status in which
      abstinence significantly reduced performance, as well as a main effect of
      encoding condition (divided attention < full attention), were found. Our results
      demonstrate that there may be substantial sex differences in the cognitive
      effects of tobacco abstinence. While preliminary, the data suggest the need for
      further, more extensive study of how males and females differ during tobacco
      abstinence. Such information will inform the best strategies for tobacco
      cessation efforts.

PMID- 22369670
TI  - Delay discounting decreases in those completing treatment for opioid dependence.
AB  - Several studies examining both control and substance-dependent populations have
      found delay discounting to remain stable over time. In this report, we examine
      whether delay discounting changes in opioid-dependent individuals who complete a
      12-week treatment. The 159 subjects who completed discounting assessments at
      baseline and treatment-end come from two separate clinical trials: 56 from Chopra
      et al. (2009) and 103 from Christensen et al. (2012). Mean discounting at 12
      weeks significantly decreased to less than half (44.8%) of the baseline level
      (95% CIs (27.5, 73.2)). Analyzing each subject's discounting data individually,
      over 3 times (95% CIs (1.9, 5.5)) as many subjects statistically decreased their
      discounting from their own baseline levels than those who exhibited a statistical
      increase. Though we failed to find any relationship among discounting measures
      and abstinence outcomes, the results from this large study suggest that treatment
      for substance dependence promotes decreases in delay discounting.

PMID- 22369671
TI  - Beyond self-reports: drinking motives predict grams of consumed alcohol in wine
      tasting sessions.
AB  - The link between drinking motives and alcohol-related outcomes has been
      investigated extensively, yet almost exclusively using retrospective self-reports
      that are subject to recall bias. This study overcomes this limitation using an
      experimental design to test whether the 4 drinking-motive dimensions (social,
      enhancement, coping and conformity, as measured in the baseline questionnaire)
      predict the quantity of alcohol actually ingested during 2 wine-tasting sessions
      conducted approximately 3 and 7 weeks after the baseline motive assessment.
      Regression modeling was based on an analog measurement of grams of pure alcohol
      among 123 young adults. Self-reported data at baseline concurred with the data
      collected during the experimental sessions, that is, alcohol consumption was high
      for males and enhancement drinkers and low for conformity drinkers. Coping
      drinkers significantly increased their consumption between the first and second
      sessions, while social drinkers tended to decrease theirs. Yet when separately
      considering data recorded during the first session, none of the drinking motives
      predicted the amounts of alcohol actually consumed. To conclude, this study
      demonstrates that motives predict actual alcohol consumption, which is consistent
      with evidence-based self-reports. Particularly, enhancement and coping drinkers
      seem to take advantage of the drinking situation probably because they usually
      appreciate the psychoactive properties of alcohol, either to maximize pleasurable
      sensations or to alleviate negative ones. However, if the setting is unusual
      (first tasting session), situational characteristics may "overrule" the effect of
      personal motives.

PMID- 22369672
TI  - A variable pressure method for characterizing nanoparticle surface charge using
      pore sensors.
AB  - A novel method using resistive pulse sensors for electrokinetic surface charge
      measurements of nanoparticles is presented. This method involves recording the
      particle blockade rate while the pressure applied across a pore sensor is varied.
      This applied pressure acts in a direction which opposes transport due to the
      combination of electro-osmosis, electrophoresis, and inherent pressure. The
      blockade rate reaches a minimum when the velocity of nanoparticles in the
      vicinity of the pore approaches zero, and the forces on typical nanoparticles are
      in equilibrium. The pressure applied at this minimum rate can be used to
      calculate the zeta potential of the nanoparticles. The efficacy of this variable
      pressure method was demonstrated for a range of carboxylated 200 nm polystyrene
      nanoparticles with different surface charge densities. Results were of the same
      order as phase analysis light scattering (PALS) measurements. Unlike PALS
      results, the sequence of increasing zeta potential for different particle types
      agreed with conductometric titration.

PMID- 22369673
TI  - A quantitative analysis of clinical trial designs in spinal cord injury based on
      ICCP guidelines.
AB  - Clinical studies of spinal cord injury (SCI) have evolved into multidisciplinary
      programs that investigate multiple types of neurological deficits and sequelae.
      In 2007, the International Campaign for Cures of SCI Paralysis (ICCP) proposed
      best practices for interventional trial designs, end-points, and inclusion
      criteria. Here we quantitatively assessed the extent to which SCI trials follow
      ICCP guidelines and reflect the overall patient population. We obtained data for
      all 288 SCI trials in ClinicalTrials.gov. We calculated summary statistics and
      observed trends pre-2007 versus 2007 onward. To compare the trial population to
      the overall SCI population, we obtained statistics from the National SCI
      Statistical Center. We generated tag clouds to describe heterogeneous trial
      outcomes. Most interventional studies were randomized (147, 73.1%), and utilized
      active (55, 36.7%) or placebo controls (49, 32.7%), both increasing trends
      (p=0.09). Most trials were open label (116, 53.5%), rather than double- (62,
      28.6%) or single-blinded (39, 18.0%), but blinding has increased (p=0.01). Tag
      clouds of outcomes suggest an emphasis on assessment using scores and scales.
      Inclusion criteria related to American Spinal Injury Association (ASIA) status
      and neurological level allowed inclusion of most SCI patients. Age inclusion
      criteria were most commonly 18-65 or older. Consistent with ICCP recommendations,
      most trials were randomized and controlled, and blinding has increased. Age
      inclusion criteria skew older than the overall population. ASIA status criteria
      reflect the population, but neurological lesion criteria could be broadened.
      Investigators should make trial designs and results available in a complete
      manner to enable comparisons of populations and outcomes.

PMID- 22369674
TI  - New insights into the source of decadal increases of dissolved organic matter in
      acid-sensitive lakes of the northeastern United States.
AB  - The last several decades have seen decreases in SO(4)(2-) deposition across the
      northeastern United States. As a result, SO(4)(2-) concentrations in lakes and
      streams have also decreased and many surface water bodies have become less
      acidic. During the same time period, there has been a concurrent increase in
      dissolved organic carbon (DOC) concentrations in many lakes and streams. We used
      fluorescence spectroscopy to characterize the dissolved organic matter (DOM)
      quality of archived samples from nine acid-sensitive lakes in Maine collected
      between 1993 and 2009, and determined that increased DOM contributions to lakes
      were primarily derived from litter and soil. All five lakes with increasing DOC
      trends demonstrated significant decreasing (i.e., more terrestrial) trends in
      fluorescence index (FI) and significant positive correlations between SO(4)(2-)
      and FI. This study used the chemical signature of terrestrial DOM to support the
      hypothesis that increased DOC concentrations in lakes and streams are driven by
      declining acid deposition and increased solubility of soil organic matter across
      a large area of the landscape.

PMID- 22369675
TI  - Determinants of adult functional outcome in adolescents receiving special
      educational assistance.
AB  - BACKGROUND: This study investigates the role of IQ, autistic traits and
      challenging behaviours in affecting adult outcomes among adolescents who receive
      special educational assistance. METHODS: A total of 58 participants were
      recruited from an ongoing longitudinal study. All received assessments of IQ,
      behavioural patterns (using the Childhood Behaviour Checklist - CBCL) and
      autistic traits (using the Social Communication Questionnaire - SCQ) during
      adolescence and were followed up 6 years later (at a mean age of 22 years) using
      the World Health Organization Disability Assessment Schedule II (WHO-DAS II) to
      assess functional outcome. RESULTS: A significant positive relationship was found
      between CBCL score and WHO-DAS II score (beta = 0.511, P = 0.001). IQ score
      showed a negative relationship with total WHO-DAS II score (beta = -0.247, P =
      0.04). SCQ score was not found to significantly influence total WHO-DAS II score
      (beta = -0.028, P = 0.84). CONCLUSIONS: Although the role of global intellectual
      ability is important, these results stress the highly predictive value of
      adolescent behaviours on functional outcomes in adult life among young adults
      receiving special educational assistance.

PMID- 22369676
TI  - Cell-free antigens of Sporothrix brasiliensis: antigenic diversity and
      application in an immunoblot assay.
AB  - Sporotrichosis is a subcutaneous mycosis diagnosed by isolation of the fungus in
      culture. Serological tests for help in diagnosis in general do not use purified
      or recombinant antigens, because there is a paucity of described immunoreactive
      proteins, especially for the new described Sporothrix species, such as Sporothrix
      brasiliensis. This study aims to characterise antigens from S. brasiliensis and
      verify their application in serodiagnosis of sporotrichosis. An immunoblot assay
      allied with computer-based analysis was used to identify putative antigenic
      molecules in a cell-free extracts of both morphological phases of this fungus,
      and to delineate antigenic polymorphism among seven S. brasiliensis isolates and
      one S. schenckii Brazilian strain. The mycelial and yeast phase of the fungus
      originated 14 and 23 reactive bands, respectively, which were variable in
      intensity. An 85 kDa antigen, verified in the yeast phase of the fungus, was
      observed in all strains used and the immunodominant protein was identified. This
      protein, however, cross-react with serum samples from patients infected with
      other pathogens. The results show that the S. brasiliensis cell-free antigen
      extract is a single and inexpensive source of antigens, and can be applied on the
      sporotrichosis serodiagnosis.

PMID- 22369678
TI  - Cross-dehydrogenative coupling between enamino esters and ketones: synthesis of
      tetrasubstituted pyrroles.
AB  - Tetrasubstituted pyrroles have been synthesized via the cross-dehydrogenative
      coupling between enamino esters and acetone. Silver carbonate proved to be an
      effective oxidant, and no transition metal catalyst is necessary.

PMID- 22369679
TI  - Subacute oral and dermal toxicity of tert-butyl hydroperoxide in Fischer F344/N
      rats and B6C3F1 mice.
AB  - Tert-butyl hydroperoxide (TBHP) is a catalyst frequently used in oxidation and
      sulfonation reactions in the plastics industry. Since the toxicological
      evaluation of TBHP remains unknown, the National Toxicology Program (NTP)
      designed studies to characterize and compare TBHP toxicity by the dermal and oral
      (gavage) routes in male and female Fischer 344 rats and B6C3F1 mice in 14-day
      exposures. Rats and mice were administered TBHP at 22, 44, 88, 176 or 352 mg/kg
      in 0.5% aqueous methylcellulose for the gavage studies. In the dermal studies,
      mice were administered the same doses as above, while rats were administered four
      doses (22, 44, 88, 176 mg/kg) in 50% aqueous acetone. Results from the gavage
      studies revealed treatment-related decreases in survival in male rats and body
      weights in both male and female rats in the 352 mg/kg group. Clinical signs
      included post-treatment lethargy, thinness, abnormal breathing, ruffled fur,
      and/or ataxia which occurred sporadically. The male mice showed a statistically
      significant decrease in body weight in the 44, 88, 176, and 352 mg/kg groups. The
      major target organs of toxicity were the forestomach in male and female rats and
      mice, and the esophagus in male and female rats and in male mice. In addition,
      there was an increase in the absolute and relative liver weight in female mice
      with hepatocellular hypertrophy in the top-dose group only. Results from spin
      trapping experiments revealed the presence of electron paramagnetic resonance
      signals from radical adducts in the blood and organic extracts of the liver and
      kidneys of rats treated by gavage with 176 mg/kg TBHP, suggesting the involvement
      of free- radical generation. The no observed adverse effect level (NOAEL) was
      considered to be 22 mg/kg in rats and male mice, and 44 mg/kg in female mice. In
      the dermal studies, there was no effect on survival, body weight, or organ
      weights in either rats or mice. TBHP administration at the site of application
      resulted in dermal irritation, hyperkeratosis, hyperplasia, and/or inflammation
      of the epidermis and inflammation of the dermis at 176 mg/kg and above in male
      and female rats. Dermal irritation at the site of application was noted in all
      the mice exposed to 352 mg/kg TBHP. Histopathological lesions in the epidermis
      and dermis were seen in the 88-352 mg/kg males and in the 176-352 mg/kg females.
      The NOAEL was found to be 88 mg/kg for male rats and female mice, and 44 mg/kg
      for female rats and male mice. In conclusion, these studies demonstrate that TBHP
      is metabolized to free radicals and is a contact irritant affecting skin by the
      dermal route of exposure, and forestomach and esophagus by oral administration.
      There was no evidence of systemic absorption by the dermal route of exposure
      based on lack of pathological findings (Supported by National Institute of
      Environmental Health Sciences Contract No. N01-ES-65406).

PMID- 22369677
TI  - Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk
      factors in Nigeria.
AB  - BACKGROUND: Data on adverse drug reactions (ADRs) related to antiretroviral (ARV)
      use in public health practice are few indicating the need for ART safety
      surveillance in clinical care. OBJECTIVES: To evaluate the incidence, type and
      risk factors associated with adverse drug reactions (ADRs) among patients on
      antiretroviral drugs (ARV). METHODS: Patients initiated on ARVs between May 2006
      and May 2009 were evaluated in a retrospective cohort analysis in three health
      facilities in Nigeria. Regimens prescribed include nucleoside backbone of
      zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in
      combination with either nevirapine (NVP) or efavirenz (EFV). Generalized
      Estimating Equation (GEE) model was used to identify risk factors associated with
      occurrence of ADR. RESULTS: 2650 patients were followed-up for 2456 person-years
      and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more
      females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall,
      61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring
      in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and
      skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening
      (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in
      patients on longer duration of ART compared to the first six months on treatment;
      6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16
      0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in
      patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9)
      respectively. Age, gender and CD4 count were not significantly associated with
      ADRs. CONCLUSION: ADRs are more likely to occur within the first six months on
      treatment. Close monitoring within this period is required to prevent occurrence
      of severe ADR and improve ART adherence. Further research on the tolerability of
      tenofovir in this environment is recommended.

PMID- 22369680
TI  - Thyroid function is maintained despite increased oxidative stress in mice lacking
      selenoprotein biosynthesis in thyroid epithelial cells.
AB  - AIMS: We have tested the hypothesis that selenium (Se)-containing antioxidative
      enzymes protect thyroid epithelial cells from oxidative damage associated with
      enzymatic production of hydrogen peroxide required for thyroid hormone
      biosynthesis. Thyroid epithelial cells therefore express antioxidative enzymes,
      including catalase, peroxiredoxins, thioredoxin reductases, and glutathione
      peroxidases (GPxs). The latter two enzyme families contain highly active peroxide
      degrading enzymes that carry selenocysteine (Sec) in their active centers. Since
      low Se status has been associated with thyroid disorders, selenoproteins are
      considered essential for thyroid integrity and function. We have conditionally
      inactivated selenoprotein biosynthesis in thyrocytes by targeting Sec tRNA.
      RESULTS: Constitutive and inducible Cre/loxP-mediated recombination of
      tRNA([Ser]Sec) drastically reduced activities of selenoenzymes GPx and type I
      deiodinase in thyroid extracts. Immunohistochemical staining revealed increased 4
      hydroxynonenal and 3-nitro-tyrosine levels consistent with increased oxidative
      stress. However, gross thyroid morphology remained intact for at least 6 months
      after recombination. Circulating thyroid hormone levels remained normal in mutant
      mice, while thyrotropin (TSH) levels were moderately elevated. Challenging mutant
      mice with low iodine diet increased TSH, but did not lead to destruction of
      selenoprotein-deficient thyroids. INNOVATION: This is the first report probing
      the assumed physiological roles of selenoproteins in the thyroid using a genetic
      loss-of-function approach. CONCLUSION: We conclude that selenoproteins protect
      thyrocytes from oxidative damage and modulate thyroid hormone biosynthesis, but
      are not essential for thyrocyte survival.

PMID- 22369681
TI  - Changes in predicted protein disorder tendency may contribute to disease risk.
AB  - BACKGROUND: Recent studies suggest that many proteins or regions of proteins lack
      3D structure. Defined as intrinsically disordered proteins, these
      proteins/peptides are functionally important. Recent advances in next generation
      sequencing technologies enable genome-wide identification of novel nucleotide
      variations in a specific population or cohort. RESULTS: Using the exonic single
      nucleotide variations (SNVs) identified in the 1,000 Genomes Project and
      distributed by the Genetic Analysis Workshop 17, we systematically analysed the
      genetic and predicted disorder potential features of the non-synonymous
      variations. The result of experiments suggests that a significant change in the
      tendency of a protein region to be structured or disordered caused by SNVs may
      lead to malfunction of such a protein and contribute to disease risk.
      CONCLUSIONS: After validation with functional SNVs on the traits distributed by
      GAW17, we conclude that it is valuable to consider structure/disorder tendencies
      while prioritizing and predicting mechanistic effects arising from novel genetic
      variations.

PMID- 22369682
TI  - Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for
      the prevention of recurrent haemorrhage after combined endoscopic haemostasis of
      bleeding peptic ulcers.
AB  - BACKGROUND: The optimal dosage of intravenous proton pump inhibitors (PPIs) for
      the prevention of peptic ulcer rebleeding remains unclear. AIM: To compare the
      rebleeding rate of high-dose and standard-dose PPI use after endoscopic
      haemostasis. METHODS: A total of 201 patients with bleeding ulcers undergoing
      endoscopic treatment with epinephrine injection and heater probe
      thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus,
      followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen
      (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40
      mg pantoprazole daily orally for 27 days. RESULTS: There were no statistical
      differences in mean units of blood transfused, length of hospitalisation ?5 days,
      surgical or radiological interventions and mortality within 30 days between two
      groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence
      interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients
      (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox
      regression analysis showed end-stage renal disease, haematemesis, chronic
      obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76
      204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for
      rebleeding and Helicobacter pylori infection was associated with lower risk of
      rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94). CONCLUSIONS: Following
      combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis
      and H. pylori Status, but not PPI dosage, are associated with rebleeding
      (http://www.Clinical Trials.gov.ID: NCT00709046).

PMID- 22369683
TI  - Strategies of exploitation of mammalian reservoirs by Bartonella species.
AB  - Numerous mammal species, including domestic and wild animals such as ruminants,
      dogs, cats and rodents, as well as humans, serve as reservoir hosts for various
      Bartonella species. Some of those species that exploit non-human mammals as
      reservoir hosts have zoonotic potential. Our understanding of interactions
      between bartonellae and reservoir hosts has been greatly improved by the
      development of animal models for infection and the use of molecular tools
      allowing large scale mutagenesis of Bartonella species. By reviewing and
      combining the results of these and other approaches we can obtain a comprehensive
      insight into the molecular interactions that underlie the exploitation of
      reservoir hosts by Bartonella species, particularly the well-studied interactions
      with vascular endothelial cells and erythrocytes.

PMID- 22369684
TI  - Short forms of the Social Interaction Anxiety Scale and the Social Phobia Scale.
AB  - Mattick and Clarke's (1998) Social Interaction Anxiety Scale (SIAS) and Social
      Phobia Scale (SPS) are commonly used self-report measures that assess 2
      dimensions of social anxiety. Given the need for short, readable measures, this
      research proposes short forms of both scales. Item-level analyses of readability
      characteristics of the SIAS and SPS items led to the selection of 6 items from
      each scale for use in the short forms. The SIAS and SPS short forms had reading
      levels at approximately the 6th and 5th grade level, respectively. Results using
      nonclinical (Study 1: N = 469) and clinical (Study 2: N = 145) samples identified
      these short forms as being factorially sound, possessing adequate internal
      consistency, and having strong convergence with their full-length counterparts.
      Moreover, these short forms showed convergence with other measures of social
      anxiety, showed divergence from measures assessing related constructs, and
      predicted concurrent interpersonal functioning. Recommendations for the use of
      these short forms are discussed.

PMID- 22369685
TI  - Targeted therapy of hepatocellular carcinoma: present and future.
AB  - Following the encouraging results of sorafenib in advanced hepatocellular
      carcinoma (HCC), targeted therapy has become a new direction of research in the
      treatment of HCC. Emerging data provide evidence that the pathogenesis and
      progression of HCC are mediated by a number of molecular defects and dysregulated
      pathways. Novel targeted therapies are designed to inhibit the aberrant pathways
      at a molecular level with an aim to improve the clinical outcome. For the past
      few years, an increasing number of targeted agents have been tested in HCC in the
      clinical setting. This review aims to summarize the current status of clinical
      development of targeted therapy in HCC, with focus on novel agents targeting
      angiogenesis, signal transduction and epigenetic dysregulation of tumors. The
      review also discusses the lessons learned from outcomes of completed clinical
      trials and provides perspectives on future clinical trials in HCC.

PMID- 22369686
TI  - Foam consolidation and drainage.
AB  - A theoretical model of foam as a consolidating continuum is proposed. The general
      model is applied to foam in a gravity settler. It is predicted that liquid
      drainage from foam in a gravity settler begins with a slow drainage stage. Next,
      a stage with faster drainage occurs where the drainage rate doubles compared to
      the initial stage. The experiments conducted within the framework of this work
      confirmed the theoretical predictions and allowed measurements of foam
      characteristics. Foams of three different concentrations of Pantene Pro-V Classic
      Care Solutions shampoo were studied, as well as the addition of polyethylene
      oxide (PEO) in one case. The shampoo's main foaming components are sodium lauryl
      sulfate and sodium laureth sulfate. It is shown to what extent foam drainage is
      slowed down by using higher shampoo concentrations and how it is further
      decreased by adding polymer (PEO).

PMID- 22369687
TI  - GPMiner: an integrated system for mining combinatorial cis-regulatory elements in
      mammalian gene group.
AB  - BACKGROUND: Sequence features in promoter regions are involved in regulating gene
      transcription initiation. Although numerous computational methods have been
      developed for predicting transcriptional start sites (TSSs) or transcription
      factor (TF) binding sites (TFBSs), they lack annotations for do not consider some
      important regulatory features such as CpG islands, tandem repeats, the TATA box,
      CCAAT box, GC box, over-represented oligonucleotides, DNA stability, and GC
      content. Additionally, the combinatorial interaction of TFs regulates the gene
      group that is associated with same expression pattern. To investigate gene
      transcriptional regulation, an integrated system that annotates regulatory
      features in a promoter sequence and detects co-regulation of TFs in a group of
      genes is needed. RESULTS: This work identifies TSSs and regulatory features in a
      promoter sequence, and recognizes co-occurrence of cis-regulatory elements in co
      expressed genes using a novel system. Three well-known TSS prediction tools are
      incorporated with orthologous conserved features, such as CpG islands, nucleotide
      composition, over-represented hexamer nucleotides, and DNA stability, to
      construct the novel Gene Promoter Miner (GPMiner) using a support vector machine
      (SVM). According to five-fold cross-validation results, the predictive
      sensitivity and specificity are both roughly 80%. The proposed system allows
      users to input a group of gene names/symbols, enabling the co-occurrence of TFBSs
      to be determined. Additionally, an input sequence can also be analyzed for
      homogeneity of experimental mammalian promoter sequences, and conserved
      regulatory features between homologous promoters can be observed through cross
      species analysis. After identifying promoter regions, regulatory features are
      visualized graphically to facilitate gene promoter observations. CONCLUSIONS: The
      GPMiner, which has a user-friendly input/output interface, has numerous benefits
      in analyzing human and mouse promoters. The proposed system is freely available
      at http://GPMiner.mbc.nctu.edu.tw/.

PMID- 22369688
TI  - A rigorous approach to facilitate and guarantee the correctness of the genetic
      testing management in human genome information systems.
AB  - BACKGROUND: Recent medical and biological technology advances have stimulated the
      development of new testing systems that have been providing huge, varied amounts
      of molecular and clinical data. Growing data volumes pose significant challenges
      for information processing systems in research centers. Additionally, the
      routines of genomics laboratory are typically characterized by high parallelism
      in testing and constant procedure changes. RESULTS: This paper describes a formal
      approach to address this challenge through the implementation of a genetic
      testing management system applied to human genome laboratory. We introduced the
      Human Genome Research Center Information System (CEGH) in Brazil, a system that
      is able to support constant changes in human genome testing and can provide
      patients updated results based on the most recent and validated genetic
      knowledge. Our approach uses a common repository for process planning to ensure
      reusability, specification, instantiation, monitoring, and execution of
      processes, which are defined using a relational database and rigorous control
      flow specifications based on process algebra (ACP). The main difference between
      our approach and related works is that we were able to join two important
      aspects: 1) process scalability achieved through relational database
      implementation, and 2) correctness of processes using process algebra.
      Furthermore, the software allows end users to define genetic testing without
      requiring any knowledge about business process notation or process algebra.
      CONCLUSIONS: This paper presents the CEGH information system that is a Laboratory
      Information Management System (LIMS) based on a formal framework to support
      genetic testing management for Mendelian disorder studies. We have proved the
      feasibility and showed usability benefits of a rigorous approach that is able to
      specify, validate, and perform genetic testing using easy end user interfaces.

PMID- 22369690
TI  - An analysis of the work of child and adolescent mental health nurses in an
      inpatient unit in Australia.

PMID- 22369689
TI  - Instability of (CTG)n*(CAG)n trinucleotide repeats and DNA synthesis.
AB  - Expansion of (CTG)n*(CAG)n trinucleotide repeat (TNR) microsatellite sequences
      is the cause of more than a dozen human neurodegenerative diseases. (CTG)n and
      (CAG)n repeats form imperfectly base paired hairpins that tend to expand in vivo
      in a length-dependent manner. Yeast, mouse and human models confirm that
      (CTG)n*(CAG)n instability increases with repeat number, and implicate both DNA
      replication and DNA damage response mechanisms in (CTG)n*(CAG)n TNR expansion and
      contraction. Mutation and knockdown models that abrogate the expression of
      individual genes might also mask more subtle, cumulative effects of multiple
      additional pathways on (CTG)n*(CAG)n instability in whole animals. The
      identification of second site genetic modifiers may help to explain the
      variability of (CTG)n*(CAG)n TNR instability patterns between tissues and
      individuals, and offer opportunities for prognosis and treatment.

PMID- 22369691
TI  - Comparative analysis and assessment of M. tuberculosis H37Rv protein-protein
      interaction datasets.
AB  - BACKGROUND: M. tuberculosis is a formidable bacterial pathogen. There is thus an
      increasing demand on understanding the function and relationship of proteins in
      various strains of M. tuberculosis. Protein-protein interactions (PPIs) data are
      crucial for this kind of knowledge. However, the quality of the main available M.
      tuberculosis PPI datasets is unclear. This hampers the effectiveness of research
      works that rely on these PPI datasets. Here, we analyze the two main available M.
      tuberculosis H37Rv PPI datasets. The first dataset is the high-throughput B2H PPI
      dataset from Wang et al's recent paper in Journal of Proteome Research. The
      second dataset is from STRING database, version 8.3, comprising entirely of H37Rv
      PPIs predicted using various methods. We find that these two datasets have a
      surprisingly low level of agreement. We postulate the following causes for this
      low level of agreement: (i) the H37Rv B2H PPI dataset is of low quality; (ii) the
      H37Rv STRING PPI dataset is of low quality; and/or (iii) the H37Rv STRING PPIs
      are predictions of other forms of functional associations rather than direct
      physical interactions. RESULTS: To test the quality of these two datasets, we
      evaluate them based on correlated gene expression profiles, coherent informative
      GO term annotations, and conservation in other organisms. We observe a
      significantly greater portion of PPIs in the H37Rv STRING PPI dataset (with score
      >= 770) having correlated gene expression profiles and coherent informative GO
      term annotations in both interaction partners than that in the H37Rv B2H PPI
      dataset. Predicted H37Rv interologs derived from non-M. tuberculosis experimental
      PPIs are much more similar to the H37Rv STRING functional associations dataset
      (with score >= 770) than the H37Rv B2H PPI dataset. H37Rv predicted physical
      interologs from IntAct also show extremely low similarity with the H37Rv B2H PPI
      dataset; and this similarity level is much lower than that between the S. aureus
      MRSA252 predicted physical interologs from IntAct and S. aureus MRSA252 pull-down
      PPIs. Comparative analysis with several representative two-hybrid PPI datasets in
      other species further confirms that the H37Rv B2H PPI dataset is of low quality.
      Next, to test the possibility that the H37Rv STRING PPIs are not purely direct
      physical interactions, we compare M. tuberculosis H37Rv protein pairs that
      catalyze adjacent steps in enzymatic reactions to B2H PPIs and predicted PPIs in
      STRING, which shows it has much lower similarities with the B2H PPIs than with
      STRING PPIs. This result strongly suggests that the H37Rv STRING PPIs more likely
      correspond to indirect relationships between protein pairs than to B2H PPIs. For
      more precise support, we turn to S. cerevisiae for its comprehensively studied
      interactome. We compare S. cerevisiae predicted PPIs in STRING to three
      independent protein relationship datasets which respectively comprise PPIs
      reported in Y2H assays, protein pairs reported to be in the same protein
      complexes, and protein pairs that catalyze successive reaction steps in enzymatic
      reactions. Our analysis reveals that S. cerevisiae predicted STRING PPIs have
      much higher similarity to the latter two types of protein pairs than to two
      hybrid PPIs. As H37Rv STRING PPIs are predicted using similar methods as S.
      cerevisiae predicted STRING PPIs, this suggests that these H37Rv STRING PPIs are
      more likely to correspond to the latter two types of protein pairs rather than to
      two-hybrid PPIs as well. CONCLUSIONS: The H37Rv B2H PPI dataset has low quality.
      It should not be used as the gold standard to assess the quality of other
      (possibly predicted) H37Rv PPI datasets. The H37Rv STRING PPI dataset also has
      low quality; nevertheless, a subset consisting of STRING PPIs with score >=770
      has satisfactory quality. However, these STRING "PPIs" should be interpreted as
      functional associations, which include a substantial portion of indirect protein
      interactions, rather than direct physical interactions. These two factors cause
      the strikingly low similarity between these two main H37Rv PPI datasets. The
      results and conclusions from this comparative analysis provide valuable guidance
      in using these M. tuberculosis H37Rv PPI datasets in subsequent studies for a
      wide range of purposes.

PMID- 22369692
TI  - Design and implementation of the first nationwide, web-based Chinese Renal Data
      System (CNRDS).
AB  - BACKGROUND: In April 2010, with an endorsement from the Ministry of Health of the
      People's Republic of China, the Chinese Society of Nephrology launched the first
      nationwide, web-based prospective renal data registration platform, the Chinese
      Renal Data System (CNRDS), to collect structured demographic, clinical, and
      laboratory data for dialysis cases, as well as to establish a kidney disease
      database for researchers and policy makers. METHODS: The CNRDS program uses
      information technology to facilitate healthcare professionals to create a blood
      purification registry and to deliver an evidence-based care and education
      protocol tailored to chronic kidney disease, as well as online forum for
      communication between nephrologists. The online portal https://www.cnrds.net is
      implemented as a Java web application using an Apache Tomcat web server and a
      MySQL database. All data are stored in a central databank to establish a Chinese
      renal database for research and publication purposes. RESULTS: Currently, over
      270,000 clinical cases, including general patient information, diagnostics,
      therapies, medications, and laboratory tests, have been registered in CNRDS by
      3,669 healthcare institutions qualified for hemodialysis therapy. At the 2011
      annual blood purification forum of the Chinese Society of Nephrology, the CNRDS
      2010 annual report was reviewed and accepted by the society members and
      government representatives. CONCLUSIONS: CNRDS is the first national, web-based
      application for collecting and managing electronic medical records of patients
      with dialysis in China. It provides both an easily accessible platform for
      nephrologists to store and organize their patient data and acts as a
      communication platform among participating doctors. Moreover, it is the largest
      database for treatment and patient care of end-stage renal disease (ESRD)
      patients in China, which will be beneficial for scientific research and
      epidemiological investigations aimed at improving the quality of life of such
      patients. Furthermore, it is a model nationwide disease registry, which could
      potentially be used for other diseases.

PMID- 22369694
TI  - Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical
      outcome of renal transplantation.
AB  - We retrospectively examined the association of polymorphisms in the CYP3A,
      CYP2J2, CYP2C8, and ABCB1 genes with pharmacokinetic (PKs) and pharmacodynamic
      (PDs) parameters of tacrolimus in 103 renal transplant recipients for a period of
      1 year. CYP3A5 expressers had lower predose concentrations (C(0) )/dose and
      higher dose requirements than nonexpressers throughout the study. Among CYP3A5*1
      carriers, those also carrying the CYP3A4*1B allele showed the lowest C(0) /dose,
      as compared with CYP3A4*1/CYP3A5*3 carriers (54.28+/-26.45, 59.12+/-24.00,
      62.43+/-41.12, and 57.01+/-17.34 vs. 112.37+/- 76.60, 123.21+/-59.57, 163.34+/
      76.23, and 183.07+/-107.82 at 1 week, 1 month, 5 months, and 1 year after
      transplantation). In addition, CYP3A4*1B/CYP3A5*1 carriers showed significantly
      lower dose-corrected exposure than CYP3A4*1/CYP3A5*1 carriers 1 year after
      transplantation (57.01+/-17.34 vs. 100.09+/-24.78; P=0.016). Only the ABCB1 TGC
      (3435-2677-1236) haplotype showed a consistent association with PDs
      (nephrotoxicity; OR=4.73; CI: 1.3-16.7; P=0.02). Our findings indicate that the
      CYP3A4*1B-CYP3A5*1 haplotype may have a more profound impact in tacrolimus PKs
      than the CYP3A5*1 allele. This study does not support a critical role of the
      CYP450 or ABCB1 single nucleotide polymorphisms in the occurrence of toxicity or
      acute rejection in renal transplant recipients treated with tacrolimus.

PMID- 22369693
TI  - Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an
      alternative pathway of macrophage activation after spinal cord injury in mice.
AB  - BACKGROUND: Recent in vivo and in vitro studies in non-neuronal and neuronal
      tissues have shown that different pathways of macrophage activation result in
      cells with different properties. Interleukin (IL)-6 triggers the classically
      activated inflammatory macrophages (M1 phenotype), whereas the alternatively
      activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this
      study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL
      6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on
      macrophage activation and the inflammatory response in the acute phase after
      spinal cord injury (SCI) in mice. METHODS: MR16-1 antibodies versus isotype
      control antibodies or saline alone were administered immediately after thoracic
      SCI in mice. SC tissue repair was compared between the two groups by Luxol fast
      blue (LFB) staining for myelination and immunoreactivity for the neuronal markers
      growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for
      locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)
      gamma and tumor necrosis factor-alpha) and Th2 cytokines (IL-4, IL-13) was
      determined by immunoblot analysis. The presence of M1 (inducible nitric oxide
      synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206
      positive) macrophages was determined by immunohistology. Using flow cytometry, we
      also quantified IFN-gamma and IL-4 levels in neutrophils, microglia, and
      macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and
      microglia. RESULTS: LFB-positive spared myelin was increased in the MR16-1
      treated group compared with the controls, and this increase correlated with
      enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale
      scores. Immunoblot analysis of the MR16-1-treated samples identified
      downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive,
      CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC
      of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206
      positive M2 macrophages, with preferential localization of these cells at the
      injury site. MR16-1 treatment suppressed the number of IFN-gamma-positive
      neutrophils, and increased the number of microglia present and their positivity
      for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment
      increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic
      behavior. CONCLUSION: The results suggest that temporal blockade of IL-6
      signaling after SCI abrogates damaging inflammatory activity and promotes
      functional recovery by promoting the formation of alternatively activated M2
      macrophages.

PMID- 22369696
TI  - Recent research on aetiology, development and phenomenology of self-injurious
      behaviour in people with intellectual disabilities: a systematic review and
      implications for treatment.
AB  - BACKGROUND: Behavioural interventions conceptualise self-injurious behaviour
      (SIB) as developing from early repetitive behaviours through acquisition of
      homeostatic functions in regulating stimulation and subsequent shaping into SIB
      through socially mediated or automatic operant reinforcement. Despite high
      success rates, such interventions rarely completely eliminate SIB, and overall
      effectiveness has not increased since the 1960s. METHODS: Research (excluding
      studies of single genetic syndromes) on the early development, functional
      properties and phenomenology of SIB in persons with intellectual disabilities
      (IDs) published from 1999 to 2010 inclusive is reviewed. RESULTS: Despite
      evidence to support the operant shaping hypothesis, in some cases tissue-damaging
      SIB, especially head-banging, emerges at a similar or younger age than
      stereotyped behaviours or 'proto-SIB', often associated with tantrums following
      frustrative non-reward and/or abrupt situational transitions. Many young children
      show undifferentiated patterns of responding in functional analyses of SIB, and
      SIB is associated with aggression and impulsivity as well as with repetitive
      behaviour. CONCLUSIONS: One dynamic in the development of SIB may be Pavlovian
      conditioning of aggression, originally elicited by aversive events or frustrative
      non-reward, to stimuli associated with such situations. Integration into operant
      technology of interventions based on Pavlovian principles such as graduated
      exposure (with or without counterconditioning) to aversive stimuli may enhance
      the effectiveness of behavioural interventions.

PMID- 22369695
TI  - Quantitative proteomic analysis revealed 4-(methylnitrosamino)-1-(3-pyridinyl)-1
      butanone-induced up-regulation of 20S proteasome in cultured human fibroblast
      cells.
AB  - The tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridinyl)-1
      butanone (NNK), is a well-known carcinogen. Although the ability of the
      metabolically activated form of NNK to generate DNA adducts is well established,
      little is known about the cellular pathways perturbed by NNK in its native state.
      In this study, we utilized stable isotope labeling by amino acid in cell culture
      (SILAC), together with mass spectrometry, to assess the perturbation of protein
      expression in GM00637 human skin fibroblast cells upon NNK exposure. With this
      approach, we were able to quantify 1412 proteins and 137 of them were with
      significantly altered expression following NNK exposure, including the up
      regulation of all subunits of the 20S proteasome core complex. The up-regulation
      of the 20S core complex was also reflected by a significant increase in 20S
      proteasome activities in GM00637, IMR90, and MCF-7 cells upon NNK treatment.
      Furthermore, the beta-adrenergic receptor (beta-AR) antagonist propranolol could
      attenuate significantly the NNK-induced increase in proteasome activity in all
      the three cell lines, suggesting that up-regulation of the 20S proteasome may be
      mediated through the beta-AR. Additionally, we found that NNK treatment altered
      the expression levels of other important proteins including mitochondrial
      proteins, cytoskeleton-associated proteins, and proteins involved in glycolysis
      and gluconeogenesis. Results from the present study provided novel insights into
      the cellular mechanisms targeted by NNK.

PMID- 22369697
TI  - A role for Cdkl1 in the development of gastric cancer.
AB  - BACKGROUND: Cyclin-dependent kinase-like1 (CDKL1) is known as a new member of
      cyclin-dependent kinases. Whether genetic alterations of CDKL1 gene are involved
      in the development and/or progression of gastric cancer is still unknown.
      MATERIAL AND METHODS: Here, the expression of CDKL1 protein in paired specimens
      of gastric cancer tissues and corresponding normal gastric tissue (n = 66) was
      assessed by immunohistochemistry assay. We then used lentivirus-mediated knock
      down to specifically inhibit CDKL1 expression in human gastric cancer cell lines.
      Cell proliferation potential in vitro was measured by MTT and clonogenic assays.
      Cell apoptosis was assessed by flow cytometry. RESULTS: We show for the first
      time that high expression of CDKL1 protein was observed in gastric cancer tissues
      compared with matched adjacent tissues. Loss of CDKL1 function in both SGC7901
      and MGC-803 gastric cancer cells significantly decreases cellular proliferation
      and increases apoptosis (p < 0.01). Furthermore, we show that the reduction of
      CDKL1 with its siRNA stimulates the activation of Bcl-2-interacting killer (Bik)
      pro-apoptotic protein and attenuated the expression of proliferating cell nuclear
      antigen PCNA. CONCLUSION: In summary, our data suggest that CDKL1 plays an
      important regulatory role in gastric cancer cell proliferation and survival, and
      therefore, may represent a new target for therapeutic intervention.

PMID- 22369698
TI  - On the origin of siphonariid polypropionates: total synthesis of caloundrin B and
      its isomerization to siphonarin B.
AB  - Enantioselective synthesis of the enantiomer of caloundrin B was achieved by
      strategic aldol coupling of an enantiopure trioxaadamantane-containing ketone
      with a racemic pyrone-containing aldehyde via kinetic resolution. In the presence
      of imidazole, ent-caloundrin B is cleanly isomerized to ent-siphonarin B
      confirming the proposed structure and absolute configuration for caloundrin B and
      establishing that it is a plausible biosynthetic product from which siphonarin B
      and baconipyrones A and C can originate.

PMID- 22369699
TI  - Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland
      function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjogren's syndrome.
AB  - INTRODUCTION: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative
      costimulatory molecule that displays a wide range of anti-inflammatory properties
      and is currently approved to treat rheumatoid arthritis as a recombinant fusion
      protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary
      Sjogren's syndrome (pSS), we generated a recombinant adeno-associated virus
      vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human
      immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in
      C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS. METHODS: A recombinant adeno
      associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion
      protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta
      galactosidase (LacZ) were administered by retrograde cannulation of the
      submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was
      measured by ELISA and salivary glands were assessed for inflammation and
      activity. RESULTS: Recombinant CTLA4IgG blocked B7 expression on macrophages in
      vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of
      C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and
      decreased T and B cell infiltration as well as dendritic cells and macrophages in
      the glands compared with control mice. In addition a decrease in several
      proinflammatory cytokines and an increase in transforming growth factor beta-1
      (TGF-beta1) expression were also observed. CONCLUSIONS: These data suggest
      expression of CTLA4IgG in the salivary gland can decrease the inflammation and
      improve the xerostomia reported in these mice.

PMID- 22369700
TI  - A proteomic view on the developmental transfer of homologous 30 kDa lipoproteins
      from peripheral fat body to perivisceral fat body via hemolymph in silkworm,
      Bombyx mori.
AB  - BACKGROUND: A group of abundant proteins of ~30 kDa is synthesized in silkworm
      larval peripheral fat body (PPFB) tissues and transported into the open
      circulatory system (hemolymph) in a time-depended fashion to be eventually stored
      as granules in the pupal perivisceral fat body (PVFB) tissues for adult
      development during the non-feeding stage. These proteins have been shown to act
      anti-apoptotic besides being assigned roles in embryogenesis and defense.
      However, detailed protein structural information for individual PPFB and PVFB
      tissues during larval and pupal developmental stages is still missing. Gel
      electrophoresis and chromatography were used to separate the 30 kDa proteins from
      both PPFB and PVFB as well as hemolymph total proteomes. Mass spectrometry (MS)
      was employed to elucidate individual protein sequences. Furthermore, 30 kDa
      proteins were purified and biochemically characterized. RESULTS: One- and two
      dimensional gel electrophoresis (1/2D-PAGE) was used to visualize the relative
      changes of abundance of the 30 kDa proteins in PPFB and PVFB as well as hemolymph
      from day 1 of V instar larval stage to day 6 of pupal stage. Their concentrations
      were markedly increased in hemolymph and PVFB up to the first two days of pupal
      development and these proteins were consumed during development of the adult
      insect. Typically, three protein bands were observed (~29, 30, 31 kDa) in 1D
      PAGE, which were subjected to MS-based protein identification along with spots
      excised from 2D-gels run for those proteomes. Gas phase fragmentation was used to
      generate peptide sequence information, which was matched to the available
      nucleotide data pool of more than ten highly homologous insect 30 kDa
      lipoproteins. Phylogenetic and similarity analyses of those sequences were
      performed to assist in the assignment of experimentally identified peptides to
      known sequences. Lipoproteins LP1 to LP5 and L301/302 could be matched to
      peptides extracted from all bands suggesting the presence of full length and
      truncated or modified protein forms in all of them. The individual variants could
      not be easily separated by classical means of purification such as 2D-PAGE
      because of their high similarity. They even seemed to aggregate as was indicated
      by native gel electrophoresis. Multistep chromatographic procedures eventually
      allowed purification of an LP3-like protein. The protein responded to lipoprotein
      specific staining. CONCLUSIONS: In B. mori larvae and pupae, 30 kDa lipoproteins
      LP1 to LP5 and L301/302 were detected in PPFB and PVFB tissue as well as in
      hemolymph. The concentration of these proteins changed progressively during
      development from their synthesis in PPFB, transport in hemolymph to storage in
      PVFB. While the 30 kDa proteins could be reproducibly separated in three bands
      electrophoretically, the exact nature of the individual protein forms present in
      those bands remained partially ambiguous. The amino acid sequences of all known
      30 kDa proteins showed very high homology. High-resolution separation techniques
      will be necessary before MS and other structural analysis can shed more light on
      the complexity of the 30 kDa subproteome in B. mori. A first attempt to that end
      allowed isolation of a B. mori LP3-like protein, the complete structure,
      properties and function of which will now be elucidated in detail.

PMID- 22369701
TI  - Past dieting is related to rigid control and disinhibition in adolescents from
      the Quebec Family Study.
AB  - Eating behaviour traits of rigid control and disinhibition have been associated
      with body weight in both adults and adolescents. Moreover, adults reporting a
      dieting history have increased levels of unhealthy eating behaviours. Against
      this background, the present study aimed to examine the relationship between
      dieting history and eating behaviour traits in adolescents. For the purpose of
      this research, a total of sixty adolescents (aged 15 (sem 2.4) years) from the
      Quebec Family Study completed the Three-Factor Eating Questionnaire (TFEQ) and a
      questionnaire regarding eating habits. Self-reported current and past dieting
      were analysed against eating behaviour traits measured by the TFEQ, including all
      subscales. As the results revealed, few adolescents reported currently dieting (n
      3). Adolescents who reported a dieting history (23.3 %) were older (16.9 v. 14.4
      years, P < 0.001), were more likely to be female (78.6 v. 41.3 %, P < 0.05) but
      did not have a significantly higher BMI z-score (1.5 v. 0.9, P = 0.10), although
      they were more likely to be either overweight or obese (P < 0.01). After
      correcting for sex, BMI and age, adolescents who reported a dieting history had
      higher levels of rigid control and disinhibition (P < 0.05-0.0001) than those
      reporting no dieting history. A greater proportion of adolescents characterised
      by high rigid control and high disinhibition were past dieters, compared to those
      characterised by low levels of both behaviour traits (53 v. 4 %). The study
      arrived at the following conclusions: as observed in adults, adolescents with a
      history of dieting present unfavourable eating behaviour traits. These
      behavioural traits may represent an additional challenge to the long-term
      regulation of body weight.

PMID- 22369702
TI  - Special issue: 4th international meeting: methodological issues in oral health
      research - intervention studies. Preface.

PMID- 22369703
TI  - Quality of cluster randomized controlled trials in oral health: a systematic
      review of reports published between 2005 and 2009.
AB  - OBJECTIVES: To assess the quality of methods and reporting of recently published
      cluster randomized trials (CRTs) in oral health. METHODS: We searched PubMed for
      CRTs that included at least one oral health-related outcome and were published
      from 2005 to 2009 inclusive. We developed a list of criteria for assessing trial
      quality and reporting. This was influenced largely by the extended CONSORT
      statement for CRTs but also included criteria suggested by other authors. We
      examined the extent to which trials were consistent with these criteria. RESULTS:
      Twenty-three trials were included in the review. In 15 (65%) trials, clustering
      had been accounted for in sample size calculations, and in 18 (78%) authors had
      accounted for clustering in analysis. Intraclass correlation coefficients (ICCs)
      were reported for eight (35%) trials; the outcome assessor was reported as having
      been blinded to allocation in 12 (52%) trials; 17 (74%) described eligibility
      criteria at individual level, but only nine (39%) described such criteria at
      cluster level. Sixteen of 20 trials (80%), in which individuals were recruited,
      reported that individual informed consent was obtained. CONCLUSIONS: These
      results suggest that the quality of recent CRTs in oral health is relatively high
      and appears to compare favourably with other fields. However, there remains room
      for improvement. Authors of future trials should endeavour to ensure sample size
      calculations and analyses properly account for clustering (and are reported as
      such), consider the potential for recruitment/identification bias at the design
      stage, describe the steps taken to avoid this in the final report and report
      observed ICCs and cluster-level eligibility criteria.

PMID- 22369704
TI  - Methodological issues in oral health research: intervention studies.
AB  - OBJECTIVES: To provide a broad overview of methodological issues in the design
      and evaluation of intervention studies in dental public health, with particular
      emphasis on explanatory trials, pragmatic trials and complex interventions.
      METHODS: We present a narrative summary of selected publications from the
      literature outlining both historical and recent challenges in the design and
      evaluation of intervention studies and describe some recent tools that may help
      researchers to address these challenges. RESULTS: It is now recognised that few
      intervention studies in dental public health are purely explanatory or pragmatic.
      We describe the PRECIS tool which can be used by trialists to assess and display
      the position of their trial on a continuum between the extremes of explanatory
      and pragmatic trials. The tool aims to help trialists make design decisions that
      are in line with their stated aims. The increasingly complex nature of dental
      public health interventions presents particular design and evaluation challenges.
      The revised Medical Research Council (MRC) guidance for the development and
      evaluation of complex interventions which emphasises the importance of planning
      and process evaluation is a welcome development. We briefly describe the MRC
      guidance and outline some examples of complex interventions in the field of oral
      health. The role of observational studies in monitoring public health
      interventions when the conduct of RCTs is not appropriate or feasible is
      acknowledged. We describe the STROBE statement and outline the implications of
      the STROBE guidelines for dental public health. CONCLUSION: The methodological
      challenges in the design, conduct and reporting of intervention studies in oral
      health are considerable. The need to provide reliable evidence to support
      innovative new strategies in oral health policy is a major impetus in these
      fields. No doubt the 'Methodological Issues in Oral Health Research' group will
      have further opportunities to highlight this work.

PMID- 22369705
TI  - Discovering factors influencing examiner agreement for periodontal measures.
AB  - OBJECTIVES: Calibration studies are routinely performed to establish examiner
      reliability in clinical periodontal research. In these studies, each periodontal
      site is assessed in duplicate, enabling point and interval estimation of
      agreement measures. We show how these data can be used additionally to discover
      subgroups among the periodontal sites according to degree of agreement with true
      periodontal status and to identify factors associated with examiner bias.
      METHODS: A Bayesian hierarchical model is developed that, for all examiners,
      links the examiner's recorded measurement with the site's true periodontal
      status, allowing for site-specific examiner effects on the recorded measurement.
      These site-specific examiner effects are modeled as arising from a Dirichlet
      process mixture, which yields a small number (relative to the number of sites) of
      distinct effects for each examiner. Hence, sites that share the same examiner
      effect form a subgroup for which that examiner exhibits consistent bias relative
      to truth. We fit this model to data from a pilot calibration study for probed
      pocket depth measurements and use the results to explore examiner-specific
      groupings of sites according to degree of agreement with true pocket depth. The
      discovered group assignments were then associated with characteristics of the
      site. RESULTS: The Bayesian hierarchical modeling revealed that periodontal sites
      were grouped according to bias into three, two, and two subgroups, respectively,
      for each of the three study examiners. The magnitude of the bias was associated
      with tooth position and true depth of the pocket. CONCLUSIONS: Our Bayesian
      hierarchical model enhances the utility of data obtained from calibration studies
      for periodontal pocket depth by facilitating discovery of subgroups of sites
      according to examiner bias. The results indicate that targeting specific tooth
      locations and pocket depths during examiner training, uniquely for each examiner,
      may reduce bias in periodontal pocket depth measurements, thereby enhancing the
      quality of oral epidemiologic research.

PMID- 22369706
TI  - Dealing with misclassification and missing data when estimating prevalence and
      incidence of caries experience.
AB  - OBJECTIVES: The aim of this research was to estimate the prevalence and incidence
      of caries experience (CE) in first permanent molars while dealing with
      misclassification and missing of data. METHODS: CE was modeled as a Hidden Markov
      Model in which the response variable is subject to misclassification and
      missingness. The proposed analysis extends that of Garcia-Zattera et al. (Stat
      Med 2010;29:3103) by allowing for various patterns of missing data. Findings were
      illustrated using data from the Signal Tandmobiel study that is a longitudinal
      oral health intervention study. RESULTS: Differences in the parameter estimates
      were noted between models that take into account misclassification and missing
      data and those that do not. Unbiased parameter estimates of prevalence and
      incidence were obtained without the use of validation data. Models that include
      subjects with missing data have smaller standard deviations than models that do
      not. CONCLUSIONS: It is important to account for misclassification to obtain less
      biased estimates of prevalence and incidence. For a proper estimation of
      prevalence and incidence in a longitudinal study subject to misclassification,
      validation data are not needed but when internal they can increase the efficiency
      in estimating the model. Also, including subjects with missing data increases the
      efficiency of estimating the parameters.

PMID- 22369707
TI  - The use of time-to-event methods in dental research: a comparison based on five
      dental journals over a 11-year period.
AB  - OBJECTIVES: Time-to-event methods are used in multivariate data analysis to
      describe the relationship between patient variables and the timing of an outcome
      event. The aims of this study were to evaluate the reporting of statistical
      techniques and results in dental research papers with special reference to time
      to-event (TTE) methods and to create guidelines for the appropriate reporting of
      these methods. METHODS: All the original research reports published in five
      dental journals in 1996, 2001, 2005, 2006, and 2007 were reviewed. The evaluation
      covered 1985 articles that were based on the systematic collection and
      statistical analysis of research data. Differences between TTE approaches and
      others were assessed in terms of the justification for the number of cases,
      description of procedures, statistical references, software used, and statistical
      figures and tables provided. RESULTS: Fifty-six papers (2.8% of the total) used
      time-to-event methods, the frequency of which increased slightly from 1996 to
      2007 (P = 0.061). Statistical procedures were described more extensively in the
      papers, which used TTE methods. Reporting of the statistical methodology in
      papers using other methods was in general inadequate. CONCLUSIONS: TTE methods
      are underused in dental research. Authors could well take heed of these results
      when designing their research, so as to make more use of such methods and to
      present the results in a manner that is in line with the policy and presentation
      of the leading dental journals. Authors could also improve their statistical
      reporting with the help of the guidelines presented here.

PMID- 22369708
TI  - A community-randomized controlled trial against sugary snacking among infants and
      toddlers.
AB  - OBJECTIVES: We evaluated the impact of educational interventions on sugary
      snacking in infants and toddlers in Tehran, Iran. METHODS: A 6-month intervention
      was integrated into health staff duties. We assigned 12- to 15-month-olds (n =
      242) and their mothers attending the vaccination offices of 18 randomly selected
      public health centers into the following groups: pamphlet and reminder (A),
      pamphlet only (B), and one control group (C). The mothers were interviewed at
      baseline and after follow-up. We recorded the frequency of sugary snacking for
      both the children and their mothers and calculated changes over 6 months. A
      reduction in the children's snacking frequency indicated a positive outcome. The
      family's residential area (affluent/nonaffluent) indicated its socioeconomic
      level. Associations between the children's and their mothers' snacking frequency
      were assessed by means of Spearman correlation. The outcomes of each intervention
      group were compared separately to those of the control group by means of the Mann
      Whitney test. In addition, we performed intention to treat analysis. Factors
      related to a positive outcome were explained by means of logistic regression
      models. RESULTS: In all groups, the child's and mother's snacking at baseline
      correlated (r = 0.4). A positive outcome was found for 62% of the children in
      group A and for 49% and 32% in groups B and C, respectively. In group A, a
      reduction in the children's snacking frequency was found despite their
      residential area (P < 0.05). Controlling for intervention effects, the logistic
      regression model showed that residential area was unrelated to the positive
      outcome. CONCLUSIONS: Oral health education with reminders provided to mothers by
      general health staff is a valuable tool for reducing sugary snacking in infants
      and toddlers in a country with developing oral health systems.

PMID- 22369709
TI  - Estimating emergence sequences of permanent teeth in Flemish schoolchildren using
      interval-censored biplots: a graphical display of tooth emergence sequences.
AB  - OBJECTIVES: The aim of the present study was to investigate the pattern of
      emergence of permanent teeth using nonparametric techniques. MATERIALS AND
      METHODS: Data were obtained from the Signal-Tandmobiel project, a 6-year
      prospective dental study conducted in Flanders (Belgium) in which 4468 primary
      school children born in 1989 were annually examined. A new exploratory method for
      interval-censored data, the IC-biplot, was applied to estimate individual
      sequences of emergence. In addition, the method renders a nice graphical
      representation of both children and teeth in the plane where the individual
      sequences of emergence can easily be visualized. On the basis of the estimated
      individual sequences, their corresponding prevalences were calculated. RESULTS:
      The study revealed that between 7 and 13 different sequences of emergence can be
      expected depending on gender and quadrant. The prevalences of the most frequent
      sequences in girls varied from 35% to 85% depending on the quadrant, while in
      boys they varied from 28% to 32%. Most sequences in the maxilla start with 6-1-2
      and in the mandible with 1-6-2. CONCLUSIONS: The IC-biplot is a flexible
      procedure that allows an easy visualization of the pattern of emergence of
      permanent teeth. Rank orders derived from the IC-biplot confirm rank orders
      suggested earlier in the literature.

PMID- 22369710
TI  - Chronic pain and weather conditions in patients suffering from temporomandibular
      disorders: a pilot study.
AB  - OBJECTIVES: Patients with temporomandibular disorders (TMDs) often report
      increased pain in response to changes in weather conditions. Nevertheless,
      scientific evidence supporting this relationship is scarce. The aim of this study
      was to assess a potential relationship between pain intensity and meteorological
      factors, through a newly developed, portable device, in patients affected by
      chronic masticatory muscle pain. METHODS: Seven female subjects were diagnosed
      with myofascial pain of the masticatory muscles, according to RDC/TMD criteria,
      were recruited, and participated in the study. Each patient was provided with a
      portable data logger that recorded and stored weather variables (atmospheric
      pressure, air humidity, temperature) every 15 min. Patients were asked to record
      the level of perceived pain on an electronic visual analogue scale (VAS) every
      hour. The relationship between meteorological variables and pain scores was
      investigated using separate generalized least squares regression models with a
      correlation structure estimated via autoregressive integrated moving average
      models. RESULTS: Individual VAS trajectories in the study period were different.
      The effect of meteorological factors on VAS scores was statistically significant
      in five subjects, with at least one main effect and/or one two-way interaction
      between meteorological variables being significant. CONCLUSIONS: The analyses
      suggest the existence of different interindividual responses to climatic changes.
      However, the identified putative role of meteorological variables and of their
      two-way interactions suggests that further investigations on larger samples may
      be useful to assess the research question under examination.

PMID- 22369711
TI  - Dental implants and improvement of oral health-related quality of life.
AB  - OBJECTIVES: Oral health-related quality of life (OHRQoL) is a multifaceted field
      involving many factors. The aim of our study was to assess whether implant
      therapy improves OHRQoL in dental patients. METHODS: Patients receiving at least
      one implant completed a health-related questionnaire before and after the
      implantation (minimum 1.5 months). Questions covered the functional and aesthetic
      scales (AS). Paired differences in individual scores were analysed using the
      Wilcoxon signed-rank test. A univariate analysis of covariance was used to relate
      overall and scale-specific average paired differences to age, gender, marital and
      educational status. Multivariate analysis of covariance was used to assess
      interactions between the covariates and different scales of outcome. All tests
      were performed at statistical significance level alpha = 0.05. RESULTS: All
      twelve Wilcoxon tests supported an improvement in OHRQoL after implant placement.
      On the AS, the mean difference in OHRQoL scores was found to be associated with
      marital status, presence of aesthetic reasons for undergoing the surgery and
      number of front teeth replaced by implants. On the functional scale (FS), most
      significant associations were observed with the number of front teeth replaced
      via implantation, followed by the presence of chewing problems and marital
      status. The multivariate analysis helped to identify the covariates that varied
      significantly over the two scales of interest. CONCLUSIONS: Effects of covariates
      responding significantly differently on different scales should not be summarized
      using an overall univariate analysis, using paired score differences averaged
      over all items. Such effect summary would be misleading. In the present study,
      significant implant-related improvements in OHRQoL were observed on both the
      aesthetic and FS in patients with at least one implant in the front dental area.

PMID- 22369712
TI  - Orthodontic treatment attitude versus orthodontic treatment need: differences by
      gender, age, socioeconomical status and geographical context.
AB  - OBJECTIVES: To investigate the relationship between the attitude towards
      orthodontic treatment and the objective level of orthodontic need, and variables
      like gender, socioeconomic status and geographical context, among 6- to 16-year
      old children. METHODS: The attitude of 2284 Italian children towards orthodontics
      was assessed using the Child Orthodontic Attitude Survey (COAS) questionnaire,
      previously validated for Italian-speaking children. The level of orthodontic need
      was evaluated by using the Risk of Malocclusion Assessment (ROMA) Index while
      socioeconomic status (SES) was based on parental job activities. The univariate
      analysis was performed using chi-square tests to find differences between groups
      for categorical variables, while multivariate analyses were conducted using
      logistic regression models. RESULTS: Individuals with a higher SES had a
      statistically significant lower need of orthodontic treatment (P = 0.003).
      Children with a very high SES were from northern (20.8%) and central Italy
      (65.9%), while only 13.3% lived in southern Italy (P < 0.001). Logistic
      regression showed that females, older children, in-treatment subjects and
      children from the region of Puglia were more likely to have orthodontics (OR =
      2.09; 95% CI: 1.66-2.64, OR = 1.08; 95% CI: 1.01-1.15, OR = 1.48, 95% CI: 1.11
      1.97, OR = 1.43; 95% CI: 1.05-1.95, respectively). CONCLUSIONS: The orthodontic
      treatment attitude largely depends on age, gender and geographical context but is
      not influenced by the real level of orthodontic therapy need.

PMID- 22369713
TI  - Relationship between breast-feeding and adiposity in infants and pre-school
      children.
AB  - OBJECTIVES: We aimed to establish associations of duration of breast-feeding with
      mean BMI and waist circumference, as well as the likelihood of being
      overweight/obese, during early childhood. DESIGN: Cross-sectional, population
      based study. Height, weight and waist circumference were measured and BMI
      calculated. Interviewer-administered questionnaire determined whether the child
      was ever breast-fed and the duration of breast-feeding. SETTING: Sydney,
      Australia. SUBJECTS: Infants and pre-school children (n 2092) aged 1-6 years were
      examined in the Sydney Paediatric Eye Disease Study during 2007-2009. RESULTS: Of
      the children aged 1-6 years, 1270 had been breast-fed compared with 822 who were
      never breast-fed. After multivariable adjustment, 1-6-year-old children who were
      ever breast-fed compared with those who were not had significantly lower BMI,
      16.7 (se 0.1) kg/m2 v. 17.1 (se 0.2) kg/m2 (P = 0.01). Decreasing BMI was
      associated with increasing duration of breast-feeding (P trend = 0.002). After
      multivariable adjustment, each month increase in breast-feeding was associated
      with an average BMI decrease of 0.04 kg/m2 (P = 0.002) and 0.03 kg/m2 (P = 0.03)
      among children aged 1-2 years and 3-4 years, respectively. In 1-2-year-old
      children, each month increase in breast-feeding duration was associated with a
      0.06 cm decrease in waist circumference (P = 0.04). Significant associations were
      not observed among 5-6-year-old children. Children who were ever breast-fed v.
      those never breast-fed were less likely to be overweight/obese (multivariable
      adjusted OR = 0.54; 95 % CI 0.36, 0.83). CONCLUSIONS: We demonstrated a modest
      influence of breast-feeding on children's BMI during early childhood,
      particularly among those aged less than 5 years.

PMID- 22369714
TI  - Modeling and analysis of cell membrane systems with probabilistic model checking.
AB  - BACKGROUND: Recently there has been a growing interest in the application of
      Probabilistic Model Checking (PMC) for the formal specification of biological
      systems. PMC is able to exhaustively explore all states of a stochastic model and
      can provide valuable insight into its behavior which are more difficult to see
      using only traditional methods for system analysis such as deterministic and
      stochastic simulation. In this work we propose a stochastic modeling for the
      description and analysis of sodium-potassium exchange pump. The sodium-potassium
      pump is a membrane transport system presents in all animal cell and capable of
      moving sodium and potassium ions against their concentration gradient. RESULTS:
      We present a quantitative formal specification of the pump mechanism in the PRISM
      language, taking into consideration a discrete chemistry approach and the Law of
      Mass Action aspects. We also present an analysis of the system using quantitative
      properties in order to verify the pump reversibility and understand the pump
      behavior using trend labels for the transition rates of the pump reactions.
      CONCLUSIONS: Probabilistic model checking can be used along with other well
      established approaches such as simulation and differential equations to better
      understand pump behavior. Using PMC we can determine if specific events happen
      such as the potassium outside the cell ends in all model traces. We can also have
      a more detailed perspective on its behavior such as determining its reversibility
      and why its normal operation becomes slow over time. This knowledge can be used
      to direct experimental research and make it more efficient, leading to faster and
      more accurate scientific discoveries.

PMID- 22369715
TI  - Functional characterization of protein domains common to animal viruses and
      mouse.
AB  - BACKGROUND: Many viruses contain genes that originate from their hosts. Some of
      these acquired genes give viruses the ability to interfere with host immune
      responses by various mechanisms. Genes of host origin that appear commonly in
      viruses code for proteins that span a wide range of functions, from kinases and
      phosphotases, to cytokines and their receptors, to ubiquitin ligases and
      proteases. While many important cases of such lateral gene transfer in viruses
      have been documented, there has yet to be a genome-wide survey of viral-encoded
      genes acquired from animal hosts. RESULTS: Here we carry out such a survey in
      order to gain insight into the host immune system. We made the results available
      in the form of a web-based tool that allows viral-centered or host-centered
      queries to be performed (http://imm.ifrec.osaka-u.ac.jp/musvirus/). We examine
      the relationship between acquired genes and immune function, and compare host
      virus homology with gene expression data in stimulated dendritic cells and T
      cells. We found that genes whose expression changes significantly during the
      innate antiviral immune response had more homologs in animal virus than genes
      whose expression did not change or genes involved in the adaptive immune
      response. CONCLUSIONS: Statistics gathered from the MusVirus database support
      earlier reports of gene transfer from host to virus and indicate that viruses are
      more likely to acquire genes involved in innate antiviral immune responses than
      those involved in acquired immune responses.

PMID- 22369716
TI  - Breast cancer therapy based on melatonin.
AB  - The usefulness of melatonin and melatoninergic drugs in breast cancer therapy is
      based on its Selective Estrogen Receptor Modulator (SERM) and Selective Estrogen
      Enzyme Modulator (SEEM) properties. Because of the oncostatic properties of
      melatonin, its nocturnal suppression by light-at-night (LAN) has been considered
      a risk-factor for breast cancer. Melatonin's SERM actions include modulation of
      estrogen-regulated cell proliferation, invasiveness and expression of proteins,
      growth factors and proto-oncogenes (hTERT, p53, p21, TGFbeta, E-cadherin, etc.).
      These actions are observable with physiologic doses of melatonin only in cells
      expressing ERalpha, and mediated by MT1 melatonin receptors. Melatonin acts like
      a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase
      and type 1, 17beta- hydroxysteroid dehydrogenase, but stimulating that of
      estrogen sulfotransferase. This double action mechanism (SERM and SEEM), and the
      specificity for ERalpha bestows melatonin with potential advantages for breast
      cancer treatments, associated with other antiestrogenic drugs, and idea already
      patented. LAN enhances the growth of rat mammary tumors by decreasing or
      suppressing melatonin production. Epidemiologic studies have also described
      increased breast cancer risk in women exposed to LAN. Since the strongest
      suppression of nocturnal melatonin occurs with wavelength light of the blue
      spectral region, optical and lightening devices filtering the blue light spectrum
      have been proposed to avoid the risks of light-induced suppression of nocturnal
      melatonin.

PMID- 22369717
TI  - Lafora progressive myoclonus epilepsy: recent insights into cell degeneration.
AB  - Lafora disease (LD) is a fatal autosomal recessive form of progressive myoclonus
      epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual
      hallucinations, intellectual, and progressive neurologic deterioration beginning
      in adolescence. The two genes known to be involved in Lafora disease are EPM2A
      and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein
      phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two
      proteins interact with each other and, as a complex, are thought to regulate
      glycogen synthesis. It may also be considered as a disorder of carbohydrate
      metabolism because of the formation of polyglucosan inclusion bodies in neural
      and other tissues due to abnormalities of the proteins laforin or malin. The
      review also outlines important patents related to Lafora disease.

PMID- 22369718
TI  - Health services for reproductive tract infections among female migrant workers in
      industrial zones in Ha Noi, Viet Nam: an in-depth assessment.
AB  - BACKGROUND: Rural-to-urban migration involves a high proportion of females
      because job opportunities for female migrants have increased in urban industrial
      areas. Those who migrate may be healthier than those staying in the village and
      they may benefit from better health care services at destination, but the
      'healthy' effect can be reversed at destination due to migration-related health
      risk factors. The study aimed to explore the need for health care services for
      reproductive tract infections (RTIs) among female migrants working in the Sai
      Dong industrial zone as well as their services utilization. METHODS: The cross
      sectional study employed a mixed method approach. A cohort of 300 female migrants
      was interviewed to collect quantitative data. Two focus groups and 20 in-depth
      interviews were conducted to collect qualitative data. We have used frequency and
      cross-tabulation techniques to analyze the quantitative data and the qualitative
      data was used to triangulate and to provide more in-depth information. RESULTS:
      The needs for health care services for RTI were high as 25% of participants had
      RTI syndromes. Only 21.6% of female migrants having RTI syndromes ever seek helps
      for health care services. Barriers preventing migrants to access services were
      traditional values, long working hours, lack of information, and high cost of
      services. Employers had limited interests in reproductive health of female
      migrants, and there was ineffective collaboration between the local health system
      and enterprises. These barriers were partly caused by lack of health promotion
      programs suitable for migrants. Most respondents needed more information on RTIs
      and preferred to receive these from their employers since they commonly work
      shifts--and spend most of their day time at work. CONCLUSION: While RTIs are a
      common health problem among female migrant workers in industrial zones, female
      migrants had many obstacles in accessing RTI care services. The findings from
      this study will help to design intervention models for RTI among this vulnerable
      group such as communication for behavioural impact of RTI health care, fostered
      collaboration between local health care services and employer enterprises, and on
      site service (e.g. local or enterprise health clinics) strengthening.

PMID- 22369719
TI  - Patients' preferences for treatment outcomes for advanced non-small cell lung
      cancer: a conjoint analysis.
AB  - BACKGROUND: Treatment decisions for advanced non-small cell lung cancer (NSCLC)
      are complex and require trade-offs between the benefits and risks experienced by
      patients. We evaluated the benefits that patients judged sufficient to compensate
      for the risks associated with therapy for NSCLC. METHODS: Participants with a
      self-reported diagnosis of NSCLC (n=100) were sampled from an online panel in the
      United Kingdom. Eligible and consenting participants then completed a self
      administered online survey about their disease and their treatment preferences
      were assessed. This involved respondents choosing among systematically paired
      profiles that spanned eight attributes: progression-free survival [PFS], symptom
      severity, rash, diarrhoea, fatigue, nausea and vomiting, fever and infection, and
      mode of treatment administration (infusion and oral). A choice model was
      estimated using mixed-logit regression. Estimates of importance for each
      attribute level and attribute were then calculated and acceptable tradeoffs among
      attributes were explored. RESULTS: A total of 89 respondents (73% male) completed
      all choice tasks appropriately. Increases in PFS together with improvements in
      symptom severity were judged most important and increased with PFS benefit - 4
      months: 5.7; 95% CI: 3.5-7.9; 5 months: 7.1; 95% CI: 4.4-9.9; and 7 months: 10.0;
      95% CI: 6.1-13.9. However, improvements in PFS were viewed as most beneficial
      when disease symptoms were mild and as detrimental when patients had severe
      symptoms. Fatigue (5.0; 95% CI: 2.7-7.3) was judged to be the most important
      risk, followed by diarrhoea (2.8; 95% CI: 0.7-4.9), nausea and vomiting (2.1; 95%
      CI: 0.1-4.1), fever and infection (2.1; 95% CI: 0.2-4.1), and rash (2.0; 95% CI:
      0.2-3.9). Oral administration was preferred to infusion (1.8; 95% CI: 0.0-3.6).
      Patients with mild and moderate symptoms traded PFS for less risks or more
      convenience if the severe symptoms were not experienced. CONCLUSION: This study
      demonstrates the value of conjoint analysis in the study of patient preferences
      for cancer treatments. In this small sample of patients with NSCLC from the UK,
      we demonstrate that the value of improvements in PFS is conditional upon the
      severity of disease symptoms; and that risks are valued differently.

PMID- 22369720
TI  - Blockade of early and late retinal biochemical alterations associated with
      diabetes development by the selective bradykinin B1 receptor antagonist R-954.
AB  - The chronic hyperglycemia measured alongside diabetes development is associated
      with significant long-term damage and failure of various organs. In the present
      study it was shown that hyperglycemia induced early and long term increases in
      nitric oxide (NO) levels, kallikrein activity and vascular capillary permeability
      measured as plasma extravasation, and decreases of Na/K ATPase activity in
      diabetic rat retina 4 and 12 weeks after streptozotocin (STZ) injection.
      Treatment of the animals for 5 consecutive days with a novel selective bradykinin
      B(1) receptor (BKB(1)-R) antagonist R-954 (2mg/kg s.c) at the end of the 4 and 12
      week periods highly reduced NO, kallikrein and capillary permeability and
      increased Na/K ATPase activity in the retina. These results suggest that the
      BKB(1)-R receptor subtype is over-expressed during the streptozotocin-induced
      development of diabetes in rat retina as evidenced by the inhibitory effects of
      the BKB(1)-R antagonist R-954 on NO, kallikrein and vascular permeability
      increases as well as Na/K ATPase decreases. The beneficial role of the BKB(1)-R
      antagonist R-954 for the treatment of the diabetic retinopathy is also suggested.

PMID- 22369721
TI  - Construction, identification and application of HeLa cells stably transfected
      with human PEPT1 and PEPT2.
AB  - The purpose of this study was to construct stably transfected HeLa cells with
      human peptide transporters (hPEPT1/hPEPT2) and to identify the function of the
      transfected cells using the substrate JBP485 (a dipeptide) and a typical
      substrate for PEPTs, glycylsarcosine (Gly-Sar). An efficient and rapid method was
      established for the preparation and transformation of competent cells of
      Escherichia coli. After extraction and purification, hPEPT1/hPEPT2-pcDNA3 was
      transfected into HeLa cells by the liposome transfection method, respectively.
      HeLa-hPEPT1/hPEPT2 cells were selected by measuring the protein expression and
      the uptake activities of JBP485 and Gly-Sar. A simple and rapid chromatography
      tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous
      determination of JBP485 and Gly-Sar in biological samples. The Michaelis-Menten
      constant (K(m)) values of Gly-Sar uptake by the hPEPT1 and hPEPT2-expressing
      transfectants were 1.03 mM and 0.0965 mM, respectively, and the K(m) values of
      JBP485 uptake were 1.33 mM for PEPT1 and 0.144 mM for PEPT2. The uptake of Gly
      Sar was significantly inhibited by JBP485 with a K(i) value of 8.11 mM (for
      PEPT1) and 1.05 mM (for PEPT2). Maximal uptake of Gly-Sar were detected at pH 5.8
      (for PEPT1) and pH 6.5 (for PEPT2), suggesting that both HeLa-hPEPT1 and HeLa
      hPEPT2 were H(+) dependent transporters. Stably transfected HeLa-hPEPT1/HeLa
      hPEPT2 cells were constructed successfully, and the functions of hPEPT1/hPEPT2
      were identified using their substrates, JBP485 and Gly-Sar. The transfected cells
      with transporters were used to investigate drug-drug interactions (DDIs) between
      JBP485 and other substrates (cephalexin or lisinopril) of PEPT1 and PEPT2.

PMID- 22369722
TI  - What is the role of photodynamic therapy in the treatment of acne vulgaris?

PMID- 22369723
TI  - Autofluorescence endoscopy with "real-time" digital image processing in
      differential diagnostics of selected benign and malignant lesions in the
      oesophagus.
AB  - BACKGROUND: Oesophageal papilloma and Barrett's oesophagus are benign lesions
      known as risk factors of carcinoma in the oesophagus. Therefore, it is important
      to diagnose these early changes before neoplastic transformation. METHOD:
      Autofluorescence endoscopy is a fast and non-invasive method of imaging of
      tissues based on the natural fluorescence of endogenous fluorophores. The aim of
      this study was to prove the diagnostic utility of autofluorescence endoscopy with
      digital image processing in histological diagnosis of endoscopic findings in the
      upper digestive tract, primarily in the imaging of oesophageal papilloma.
      RESULTS: During the retrospective analysis of about 200 endoscopic procedures in
      the upper digestive tract, 67 cases of benign, precancerous or cancerous changes
      were found. White light endoscopy (WLE) image, single-channel (red or green)
      autofluorescence images, as well as green and red fluorescence intensities in two
      modal fluorescence image and red-to-green (R/G) ratio (Numerical Colour Value,
      NCV) were correlated with histopathologic results. The NCV analysis in
      autofluorescence imaging (AFI) showed increased R/G ratio in cancerous changes in
      96% vs. 85% in WLE. Simultaneous analysis with digital image processing allowed
      us to diagnose suspicious tissue as cancerous in all of cases. Barrett's
      metaplasia was confirmed in 90% vs. 79% (AFI vs. WLE), and 98% in imaging with
      digital image processing. In benign lesions, WLE allowed us to exclude tissue as
      malignant in 85%. Using autofluorescence endoscopy R/G ratio was increased in
      only 10% of benign changes causing the picture to be interpreted as suspicious,
      but when both methods were used together, 97.5% were cases excluded as
      malignancies. Mean R/G ratios were estimated to be 2.5 in cancers, 1.25 in
      Barrett's metaplasia and 0.75 in benign changes and were statistically
      significant (p=0.04). CONCLUSION: Autofluorescence imaging is a sensitive method
      to diagnose precancerous and cancerous early stages of the diseases located in
      oesophagus. Especially in two-modal imaging including white light endoscopy,
      autofluorescence imaging with digital image processing seems to be a useful
      modality of early diagnostics. Also in observation of papilloma changes, it
      facilitates differentiation between neoplastic and benign lesions and more
      accurate estimation of the risk of potential malignancy.

PMID- 22369724
TI  - Phototoxicity of phenothiazinium dyes against methicillin-resistant
      Staphylococcus aureus and multi-drug resistant Escherichia coli.
AB  - BACKGROUND: Photodynamic inactivation (PDI) has been investigated to cope with
      the increasing incidence of multidrug-resistant (MDR) pathogens. Here we studied
      the PDI mediated by methylene blue (MB) and toluidine blue O (TBO) in clinical
      methicillin-resistant Staphylococcus aureus and MDR Escherichia coli, together
      with their corresponding American Type Culture Collection (ATCC) strains.
      METHODS: Effect of photosensitizer concentration (12.5, 25, 50 MUg/ml) and laser
      irradiation time (10, 20 and 30 min) on lethal photosensitization was
      investigated. RESULTS: TBO was more effective. TBO at 50 MUg/ml, 46.8 J cm-2,
      exhibited 0.7 log killing for MDR E. coli and 1.7 log killing for E. coli (ATCC
      25922); 3.1 log killing for MRSA, and 4.2 log killing for S. aureus (ATCC 25923).
      MB at 50 MUg/ml, 163.8 J cm-2, only exhibited 2.2 log killing in MRSA and 3.1 log
      killing in S. aureus (ATCC 25923). MB (50 MUg/ml, 163.8 J cm-2) induced 0.2 log
      killing for MDR E. coli and 0.3 log killing for E. coli (ATCC 25922). After TBO
      PDI, MDR isolates were more susceptible to some antibiotics than control groups.
      CONCLUSION: Our studied clinical isolates were more resistant to PDI-mediated
      killing than their ATCC reference strains. Thus, TBO/MB-mediated PDI in other MDR
      isolates deserves further investigation.

PMID- 22369725
TI  - Photodiagnosis and photodynamic therapy of peritoneal metastasis of ovarian
      cancer.
AB  - Ovarian cancer is among the deadliest in women. Current treatment strategies fail
      to cure many patients owing to the difficulties of eradicating peritoneal
      implants frequently associated with this pathology. Photodynamic therapy
      represents a promising treatment as it offers many advantages over alternative
      strategies: diagnostic properties, specific targeting of abnormal cells,
      possibility to be combined with other therapies.

PMID- 22369727
TI  - The effects of PDT in primary malignant brain tumours could be improved by
      intraoperative radiotherapy.
AB  - INTRODUCTION: GBM has a poor survival despite surgery and chemoradiotherapy.
      Cytoreduction and PDT have postulated to afford better local GBM-control.
      However, the interaction of PDT with newer novel therapies had not been fully
      investigated. This study reviewed the impact of PDT in conjunction with
      intraoperative radiotherapy. METHODS: Case note review of prospectively collected
      data of GBMs treated surgically by the senior author (SE). Patients received
      standard therapy (ST), ST+PDT or ST+PDT+IORT. ST involved maximum safe resection,
      PDT involved intracavity 100 J/cm2 630 nm laser and IORT involved intracavity 10
      15 Gys using the PRS400(r). Patients were followed up clinically and
      radiologically till death. RESULTS: There were 73 patients included in this
      analysis (42 males). The average age was 59years. Thirty received PDT and 43 did
      not. The mean survival of PDT-patients was significantly longer than those had ST
      alone (62.9 weeks vs. 20.6 weeks) (p=0.001). Patients < 65 year of age survived
      longer than those >= 65 year (p=0.033). IORT on its own did not make a
      significant difference to survival (p=0.111). However the average survival for
      patients who received PDT+IORT was substantially higher than those who received
      PDT alone (79 weeks vs. 39.7 weeks). Using a Cox regression covariant analysis,
      demonstrated that PDT was the only therapy to make a statistically significant
      difference to survival (p=0.018). CONCLUSIONS: PDT in high grade glioma was
      statistically significant therapeutic modality and its effects were further
      improved by IORT.

PMID- 22369726
TI  - In vitro photodynamic effect of aluminum tetrasulfophthalocyanines on melanoma
      skin cancer and healthy normal skin cells.
AB  - Photodynamic therapy is a medical treatment that uses an inactive dye/drug and
      lasers as a light source to activate the dye/drug to produce a toxic form of
      oxygen that destroys the cancer cells. This study aimed at investigating the
      cytotoxic effects of different concentrations of aluminum
      tetrasulfophthalocyanines in its inactive and active state (laser induced) on
      melanoma skin cancer cells, healthy normal skin fibroblast and keratinocyte
      cells. Experimentally, 3 * 104 cells/ml were seeded in 24-well plates before
      treatment with different concentrations of aluminum tetrasulfophthalocyanines.
      After 2h, cells were irradiated with a light dose of 4.5 J/cm2. Post-irradiated
      cells were incubated for 24h before cell viability was measured using the
      CellTiter-Blue Viability Assay. Results showed that aluminum
      tetrasulfophthalocyanines at high concentrations were cytotoxic to melanoma cells
      in the absence of laser activation. In the presence of laser activation of
      aluminum tetrasulfophthalocyanines at a concentration of 40 MUg/ml decreased cell
      viability of melanoma cells to 45%, fibroblasts to 78% and keratinocytes to 73%.
      At this photosensitizing concentration of aluminum tetrasulfophthalocyanines the
      efficacy of the treatment light dose 4.5 J/cm2 and the cell death mechanism
      induced by photoactivated aluminum tetrasulfophthalocyanines was evaluated. A
      light dose of 4.5 J/cm2 was more efficient in killing a higher number of melanoma
      cells and a lower number of fibroblast and keratinocyte cells than the other
      light doses of 2.5 J/cm2, 7.5 J/cm2 and 10.5 J/cm2. Apoptosis features such as
      blebbing, nucleus condensation, nucleus fragmentation and the formation of
      apoptotic bodies were seen in the photodynamic therapy treated melanoma skin
      cancer cells. This in vitro photodynamic therapy study concludes that using
      aluminum tetrasulfophthalocyanines at a photosensitizing concentration of 40
      MUg/ml in combination with a laser dose of 4.5 J/cm2 was potentially lethal for
      melanoma skin cancer cells and less harmful for the normal healthy skin cells.

PMID- 22369728
TI  - Mitoxantrone as a prospective photosensitizer for photodynamic therapy of breast
      cancer.
AB  - Photodynamic therapy has the potential to become an effective alternate to
      surgery for the treatment of cancer. In recent years, there has been a focus on
      identifying more effective and less toxic photosentisizers for use in
      photodynamic therapy. The purpose of this study was to assess the effectiveness
      of mitoxantrone, a chemotherapeutic agent, as a photosensitizer for photodynamic
      therapy in the MCF-7 human breast cancer cell line. Cytotoxicity was evaluated
      for different concentrations of mitoxantrone, and photosensitivity was assessed
      using a non-coherent light source. The percentage of the cell survival after 24 h
      was investigated using the MTT assay. Overall, the results showed that
      mitoxantrone is a remarkably efficient photosensitizer that could mediate MCF-7
      cell death at a low concentration (5 MUM) with modest exposure to light. It is
      surprising to find that a chemotherapeutic agent can be an effective
      photosensitizer for PDT in vitro.

PMID- 22369729
TI  - Localization and phototoxic effect of zinc sulfophthalocyanine photosensitizer in
      human colon (DLD-1) and lung (A549) carcinoma cells (in vitro).
AB  - BACKGROUND: Photodynamic therapy (PDT) is a therapeutic modality used for
      treating cancerous cells. It has been previously shown that mixed sulfonated
      metallophthalocyanine complex, zinc sulfophthalocyanine (ZnPcS(mix)) is effective
      in destroying lung cancer cells. This study aimed to determine subcellular
      localization of ZnPcS(mix) and its effect on two cancer cell lines. METHODS:
      ZnPcS(mix) was activated at a wavelength of 680 nm with 5 J/cm2. Colon (DLD-1)
      and lung (A549) cancer cell lines were used. Subcellular localization of
      ZnPcS(mix) was determined by fluorescence microscopy. Toxicity of PS alone and
      combination of light and PS (PDT) was determined by cell morphology, viability,
      proliferation and cytotoxicity. Cells which received no irradiation (0 J/cm2),
      irradiation alone (5 J/cm2) or treated with PS alone (no irradiation) served as
      controls. RESULTS: ZnPcS(mix) localized in both lysozomes and mitochondria in
      both A549 and DLD-1 cells. A549 cells treated with PDT showed a significant
      decrease in viability and proliferation in all PS concentrations used, while in
      DLD-1 cells a significant decrease was seen with concentrations of 10, 20 and 40
      MUM. In absence of light, ZnPcS(mix) did not result in cellular toxicity in A549
      cells whereas in DLD-1 cells it resulted in a reduction in cell proliferation
      only at a concentration of 40 MUM. CONCLUSION: ZnPcS(mix) was effective in
      inducing cell death in both cell lines when localized in vital organelles such
      mitochondria and lysozomes which are essential for cell functioning.
      Photoactivated ZnPcS(mix) affected the cells at different concentration and
      yielded good therapeutic results in vitro.

PMID- 22369730
TI  - Photodiagnosis and treatment of condyloma acuminatum using 5-aminolevulinic acid
      and homemade devices.
AB  - BACKGROUND: The objective of this study was to improve the feasibility of
      applying topic 5-aminolevulinic acid (ALA) in photodiagnosis (PD) and treatment
      of condyloma caused by human papillomavirus (HPV) using two homemade handheld
      devices and to discuss the photodynamic therapy (PDT) as a suitable alternative
      for each of the cases studied. Both, protoporphyrin IX production and
      photodegradation were analyzed, and the pain experienced during the illumination
      was correlated with the light intensities. METHODS: A total of 40 women with
      different grades of lesions caused by HPV were chosen from patients of the School
      of Medicine of Ribeirao Preto (University of Sao Paulo) and of the Unit of Public
      Health of Araraquara, Sao Paulo. RESULTS: We did not encounter any unexpected
      difficulties using our devices during the treatment. The existence of an easily
      observable reddish fluorescence with large intensity concentrated on the lesions
      is the clinical indication of the penetration and the selective concentration of
      protoporphyrin IX in the clinical and subclinical lesions rather than in the
      healthy tissue. The aesthetic results were much better than those obtained by
      conventional techniques as surgery or cryogenics, with no recurrence reported
      after two years of treatment. CONCLUSIONS: Our results are proof for the various
      advantages using ALA cream for the PD and PDT in many different cases of
      condyloma by HPV. This study will be continued to investigate the PpIX
      photobleaching and the irradiance and fluence rate to optimize conducting the
      clinical trials, to improve the devices and therefore increase the treatment
      response.

PMID- 22369731
TI  - Monitoring microcirculatory alterations in oral squamous cell carcinoma following
      photodynamic therapy.
AB  - BACKGROUND: One of the mechanisms through which photodynamic therapy (PDT) is
      thought to elicit tumour destruction is by producing microvascular damage and
      obstruction of nutritive blood flow. The aim of this study was to directly
      monitor and quantify microcirculatory changes following tissue illumination by
      PDT for oral squamous cell carcinoma. METHODS: Ten consecutive patients receiving
      PDT for a carcinoma in situ, a T1 or T2 tumour in the oral cavity without
      evidence of lymph node metastasis were selected for this study. Tumour and
      marginal healthy mucosa total capillary density (TCD) and functional capillary
      density (FCD) inside the field of illumination were measured and compared using
      sidestream dark-field (SDF) imaging prior to tissue illumination, immediately
      after PDT, and again after 15min. RESULTS: Baseline mean tumour TCD was 21.2+/
      5capillaries per square millimetres (cpll/mm2) and 24.9+/-19cpll/mm2 in the
      surrounding marginal healthy tissue; there were no significant differences
      between tumour and healthy tissue or time points. Comparisons between baseline
      and post-illumination time points revealed significant differences in both tumour
      and healthy tissue FCD (P<0.05). No significant differences in FCD were observed
      between the two tissues. CONCLUSIONS: Our findings using SDF imaging demonstrate
      that PDT significantly attenuates tumour and marginal healthy tissue perfusion by
      directly disrupting the functionality of the microcirculation.

PMID- 22369732
TI  - Photodynamic therapy with hyperbranched poly(ether-ester) chlorin(e6)
      nanoparticles on human tongue carcinoma CAL-27 cells.
AB  - BACKGROUND: Hyperbranched polymers represent a new class of drug-delivery vehicle
      that can be used to prepare nanoparticles with uniform size distribution.
      METHODS: In this study we prepared covalent conjugates between the
      photosensitizer chlorin(e6) and hyperbranched poly(ether-ester), HPEE. HPEE-ce6
      nanoparticles were synthesized by carbodiimide-mediated reaction between HPEE and
      ce6, and characterized by ultraviolet-visible absorption spectroscopy (UV-Vis),
      and transmission electron microscopy (TEM). The uptake and phototoxicity of HPEE
      ce6 nanoparticles towards human oral tongue cancer CAL-27 cells was detected by
      confocal laser scanning microscopy (CLSM) and MTT assay, respectively. RESULTS:
      The absorption peak of HPEE-ce6 nanoparticles was red-shifted 12-nm compared with
      ce6, and TEM showed uniform nanoparticles with a diameter of 50-nm. HPEE-ce6
      nanoparticles were taken up by CAL-27 cells after 4h incubation and localized in
      the cytoplasm. The MTT assay showed a significantly (P<0.05) higher phototoxicity
      compared to free ce6 after 12 J/cm2 of 660-nm laser illumination. CONCLUSIONS:
      This is the first time to our knowledge that hyperbranched polymers have been
      used in PDT drug delivery.

PMID- 22369733
TI  - Treatment of Kimura disease with photodynamic therapy: a case study.
AB  - We report on the application of photodynamic therapy (PDT) in the management of
      Kimura disease. A 58-year-old Asian male was offered this modality to assess the
      possibility to control disease progression. The patient was managed with surgery
      and the disease recurred and caused facial disfigurement. PDT was offered after
      careful discussion at UCLH multidiscipline meeting. The photosensitiser "mTHPC"
      was introduced intravenously 96h prior to delivering the light under ultrasound
      guidance. Magnetic resonance images showed moderate-significant reduction of the
      disease volume. Fourteen months post-PDT, the disease started re-growing and the
      patient subsequently underwent one further round of PDT which was as successful
      as the first round in reducing the facial disfigurement. Photodynamic therapy was
      very effective in controlling disease progression in this patient who suffers
      from Kimura disease.

PMID- 22369734
TI  - Fluorescence examination and photodynamic therapy of facial squamous cell
      carcinoma--a case report.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the usefulness and feasibility of
      fluorescence examination and photodynamic therapy (PDT) for facial squamous cell
      carcinoma. METHODS: A 68-year-old male patient underwent 3 courses of PDT. The
      first treatment was carried out using topically applied 5-aminolevulinic acid
      (ALA) to the affected area (5.0 cm * 2.5 cm) 3h before light irradiation.
      ALA/PpIX-mediated fluorescence was used to visualize the lesion and its margin.
      The lesion was illuminated with a 630 nm laser at 120 J/cm2. Thirty days later,
      the residual lesion received the second treatment at the same light dose after
      topical use of ALA. Despite the tumor was treated with two courses of PDT, The
      lesion was not cleared completely yet. At last we used topical ALA and
      intravenous injection of HiPorfin, with the same light dose, then the lesion was
      cured and the patient was tumor-free followed up for over 15 months. RESULTS:
      ALA/PpIX-mediated fluorescence visualized the lesion location. Complete cure was
      achieved after the third course of ALA/Hiporfin PDT. During the 15 months of
      followed up, no recurrence was noticed. CONCLUSION: ALA assisted fluorescence
      examination can be a useful tool to visualize the malignant lesion and determine
      its margin. ALA-PDT is effective for superficial lesions, but for thicker and
      deeper lesions, systemic administration of photosensitizer is indispensable.

PMID- 22369735
TI  - Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma.
AB  - INTRODUCTION: Glioma is one of the most aggressive human tumors; however, little
      is known about its genetic risk factors. The role of heredity is likely to be
      explained by combinations of common low-risk variants. Previous studies have
      indicated that more than 100 single nucleotide polymorphisms (SNPs) are
      associated with the risk of glioma. METHODS: To further investigate how and to
      what extent these SNPs contribute to glioma susceptibility in a Chinese
      population, we analyzed 43 SNPs of 226 glioma patients and 254 normal people in
      order to evaluate the associations between SNPs and the risk of glioma. RESULTS:
      Overall, we found three protective alleles for glioma in patients: the allele "G"
      of rs1801275 in the IL4R gene by allele model (odds ratio [OR], 0.71; 95%
      confidence interval [CI], 0.50-0.99; P=0.04) and dominant model (OR, 0.67; 95%
      CI, 0.46-0.99; P=0.04) analysis respectively, the allele "T" of rs17748 in the
      TREH gene by recessive model (OR, 0.48; 95% CI, 0.23-1.01; P=0.05) analysis, and
      the allele "G" of rs6470745 in CCDC26 gene by recessive model (OR, 0.48; 95% CI,
      0.26-0.89; P=0.02) analysis. CONCLUSION: This study provides evidence for three
      glioma susceptibility genes - TREH, IL4R and CCDC26 - in a Chinese population;
      this may shed light on molecular markers of glioma susceptibility and could
      therefore be used as a diagnostic and prognostic marker for glioma patients in
      clinical study.

PMID- 22369736
TI  - A simple and economical in-house phage technique for the rapid detection of
      rifampin, isoniazid, ethambutol, streptomycin, and ciprofloxacin drug resistance
      in Mycobacterium tuberculosis, directly on decontaminated sputum samples.
AB  - OBJECTIVES: The early detection of drug resistance would be a boon for TB control
      programs. The aim of the present study was to set up a rapid phage assay for the
      testing of drug susceptibility of Mycobacterium tuberculosis to rifampin,
      isoniazid, ethambutol, streptomycin, and ciprofloxacin, directly on
      decontaminated sputum samples. METHODS: Mueller-Hinton broth was used instead of
      7H9 broth to make the method more economical. Vancomycin and polymyxin B were
      added to the concentrated sputum samples to reduce the bacterial contamination.
      The phage assay on decontaminated sputum samples was compared with the proportion
      method using M. tuberculosis isolates from the same sputum samples. RESULTS:
      Phage assay results were available within 48h for rifampin and streptomycin and
      within 72h for all the other drugs. In contrast the proportion method required 4
      6 weeks from the primary cultures. The sensitivity of the phage assay was in the
      range of 93% to 100% and specificity in the range of 96% to 100% for all the
      drugs tested. The interpretation of results was possible for 334 of the 370
      (90.3%) acid-fast bacillus (AFB) smear-positive sputum samples by the phage
      assay. CONCLUSIONS: The phage assay for the detection of drug resistance on
      direct decontaminated sputum samples is economical, easy to perform, and rapid.

PMID- 22369737
TI  - Burnout among chiropractic practitioners: real or imagined an exploratory study
      protocol.
AB  - Burnout is a psychological syndrome of emotional exhaustion, depersonalization
      and reduced personal accomplishment that has been found to exist in a significant
      number of healthcare and helping professionals. It imposes a significant societal
      burden by shortened practitioner lifespan, decreased efficiency, negative health
      outcomes and poorer levels of patient care. Theoretical models suggest that it
      appears to be the result of a complex interaction between job resources and job
      demands. It may be reasonable to conclude that Chiropractic professionals
      experience similar vocational demands and thus experience significant levels of
      occupational stress and subsequent burnout. However the data on burnout within
      the chiropractic profession is limited. It is possible that this results in
      significant negative outcomes on chiropractors and their patients. Therefore, the
      objective of this paper is to demonstrate the need to explore burnout in
      chiropractic practice and offer a research protocol for a potential study.

PMID- 22369738
TI  - Milking parlour size, pre-milking routine and stage of lactation affect
      efficiency of milking in single-operator herringbone parlours.
AB  - Efficient milking systems, in terms of labour demand, capital investment and cow
      udder health are critical to successful dairy herd expansion. The objective of
      this study was to establish the effect of two primary influencing factors on
      efficient milking performance, i.e. parlour size (number of milking units) and
      pre-milking routine (full and nil) of spring-calved cows, in a single-operator
      side-by-side, swing-over milking parlour. Efficiency parameters investigated in a
      5 * 2 factorial design included milk-flow and yield, row time, over-milking
      duration and operator idle time. Five combinations of parlour size (14, 18, 22,
      26 and 30 milking units) each with two different pre-milking routines (Full:
      spray, strip, wipe, attach clusters, and Nil: attach clusters) were examined with
      one milking operator. The trial was carried out over 40 milking sessions and cows
      (up to 120) were randomly assigned to groups (n = 14, 18, 22, 26 or 30) before
      each milking session. Row within a milking session was the experimental unit. The
      experiment was carried out at both peak and late lactation. The data were
      analysed with a mixed model using GenStat 13.2. The full pre-milking routine
      reduced time to milk let-down and milking time, increased average flow rate but
      did not affect milk yield. As milking unit number increased, the duration of over
      milking (defined as time at milk flow rate < 0.2 kg/min) increased more with a
      full compared with nil routine. Thus, the use of pre-milking preparation
      decreased milking time per cow but as parlour size increased, milking row times,
      as well as the proportion of cows that were over-milked, also increased, thereby
      reducing overall efficiency. These results have implications for milking
      management in single-operator swing-over, tandem and rotary parlours with
      seasonally calved herds.

PMID- 22369739
TI  - Nurses and ventilators.
AB  - In the previous issue of Critical Care, Rose and colleagues report the results of
      a survey on the frequency with which ICU nurses are involved in decision-making
      in ventilator management. About 63 to 88% of the decisions were made by nurses in
      collaboration with physicians, and as much as 68% of ventilator adjustments were
      performed by nurses independent of physicians. Nurse involvement in decision
      making was twice as likely in ICUs that use weaning protocols. The ICU nurse
      performs many roles, the most important being the continuous observation of a
      patient. The diversion of a nurse's attention from constant vigilance by
      performing tasks of no benefit, such as the use of weaning protocols, would be a
      most unfortunate turn of events.

PMID- 22369740
TI  - Transforming growth factor-beta1 induced epithelial-mesenchymal transition in
      hepatic fibrosis.
AB  - The epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition
      (MET) are crucial for the regulation of cellular plasticity during liver
      fibrosis. Transforming growth factor (TGF)-beta1 is an important cytokine for the
      induction of the EMT in liver fibrosis. TGF-beta1 signaling induces the EMT
      through various signaling mechanisms and is the predominant agent mediating these
      fibrotic changes. Chronic exposure to TGF-beta1 induces the transition of
      hepatocytes to collagen-producing mesenchymal cells, prolonged exposure of
      hepatocytes to TGF-beta1 increases the expression of collagen and induces
      cytoskeletal rearrangement that resembles the EMT. These morphological and
      molecular alterations may provide the foundation for liver fibrosis. This review
      discussed the relation and mechanisms between EMT and liver fibrosis and
      ulteriorly elaborated on TGF-beta1 induced EMT and each of their roles in liver
      fibrosis. Better understanding of the cellular and molecular characteristics of
      the cirrhotic hepatocyte may enable the development of chemo-preventative agents
      for liver fibrosis.

PMID- 22369741
TI  - Prospective evaluation of the factors effective on morbidity and mortality of the
      patients having liver resection surgeries.
AB  - BACKGROUND/AIMS: The objective of this study is to evaluate the factors effective
      on mortality and morbidity of the patients operated for liver tumor. METHODOLOGY:
      Thirty-four patients who were operated for liver tumor between January 1st 2008
      and December 31st 2009 in Cerrahpasa Medical Faculty have been included in this
      study. Patient preoperative, perioperative and postoperative characteristics and
      the effects of these characteristics on mortality, morbidity and the length of
      hospital stay were evaluated. RESULTS: Most common postoperative complications
      during the study were fever and surgical site infection. Nineteen of the patients
      with blood loss over 1, 000 mL had the need for postoperative ICU treatment. The
      presence of concomitant disease, especially diabetes mellitus, liver disease and
      cardiovascular diseases and more than 2 units transfusion of erythrocyte
      suspension and fresh frozen plasma were considered related to mortality and
      morbidity. CONCLUSIONS: Patient preoperative, perioperative and postoperative
      characteristics affect patient morbidity and mortality in liver resection
      surgery. Diagnosing liver tumors early and thus reducing surgical site blood loss
      and use of blood products will decrease mortality and morbidity ratios after
      liver surgeries.

PMID- 22369742
TI  - Safety of hepatectomy accompanying combined resection of other organs.
AB  - BACKGROUND/AIMS: The present study analyzed postoperative outcomes for patients
      who underwent hepatectomy accompanied by resection of other organs, to clarify
      operative safety. METHODOLOGY: We examined perioperative parameters in 95
      patients who underwent hepatectomy and other organ resections (colorectal
      resection, n=46; gastrectomy or duodenectomy, n=13; splenectomy, n=17; resection
      of diaphragm, n=9; pulmonary resection, n=4; others, n=6). RESULTS: Prevalence of
      chronic liver dysfunction (100%) or hepatocellular carcinoma (HCC) (100%) was
      significantly higher in patients who underwent splenectomy than in other groups
      (17% and 21%, respectively; p<0.01). Extent of hepatectomy, operating time and
      blood loss did not differ significantly between groups. Frequency of blood
      transfusion use was highest in patients who underwent splenectomy (p<0.01).
      Postoperative complications tended to be more frequent among patients who
      underwent splenectomy, but this difference was not significant. Wound infection
      tended to be more frequent among patients who underwent colorectal resection, but
      not significantly (p=0.11). Hepatectomy-associated complications in patients who
      underwent splenectomy most often appeared in the form of uncontrolled ascites
      (p<0.01), with hospital deaths rarely observed and hospital stay not
      significantly different between groups. CONCLUSIONS: Good postoperative outcomes
      in multi-organ resections with hepatectomy were observed by careful perioperative
      management based on adequate indications for hepatectomy.

PMID- 22369743
TI  - Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy
      in an orthotopic model of pancreatic cancer.
AB  - BACKGROUND/AIMS: Laparoscopy is important in staging pancreatic cancer, but false
      negatives remain problematic. Making tumors fluorescent has the potential to
      improve the accuracy of staging laparoscopy. METHODOLOGY: Orthotopic and
      carcinomatosis models of pancreatic cancer were established with BxPC-3 human
      pancreatic cancer cells in nude mice. Alexa488-antiCEA conjugates were injected
      via tail vein 24 hours prior to laparoscopy. Mice were examined under bright
      field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes
      measured included time to identification of primary tumor for the orthotopic
      model and number of metastases identified within 2 minutes for the carcinomatosis
      model. RESULTS: FL enabled more rapid and accurate identification and
      localization of primary tumors and metastases than BL. Using BL took
      statistically significantly longer time than FL (p<0.0001, fold change and 95% CI
      for BL vs. FL: 8.12 (4.54,14.52)). More metastatic lesions were detected and
      localized under FL compared to BL and with greater accuracy, with sensitivities
      of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough
      to detect metastatic lesions <1mm. CONCLUSIONS: The use of fluorescence
      laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody
      permits rapid detection and accurate localization of primary and metastatic
      pancreatic cancer in an orthotopic model. The results of the present report
      demonstrate the future clinical potential of fluorescence laparoscopy.

PMID- 22369744
TI  - Effect of probiotics on serum bile acids in patients with ulcerative colitis.
AB  - BACKGROUND/AIMS: Evaluation of bile acids (BA) is useful for assessing the
      changes of intestinal flora in patients with ulcerative colitis (UC). During
      enterohepatic circulation, the intestinal micro flora cause 7 alpha
      dehydroxylation of cholic acid (CA) and chenodeoxycholic acid (CDCA), yielding
      deoxycholic acid(DCA) and lithocholic acid, respectively. The aim of the present
      study was to investigate the effects of probiotics in patients with UC by
      examining changes of the serum BA profile. METHODOLOGY: Twenty-seven patients
      were divided into the following 2 groups based on endoscopic findings: Fifteen
      patients with distal UC (dUC group) and 12 patients with pancolitis (pUC group).
      After treatment with mesalazine or salazosulfapyridine (5-ASA), all patients
      achieved remission. Then they were given 5-ASA plus the probiotic Clostridium
      butyricum Miyairi (3.0 g/day) for 4 weeks. RESULTS: After 4 weeks of probiotic
      treatment, %CDCA was significantly higher and %DCA was significantly lower in the
      pUC group than in the HV group. In contrast, the dUC group showed no significant
      differences of %CDCA or %DCA from the HV group after 4 weeks. CONCLUSIONS:
      Probiotic therapy restored intestinal flora involved in 7 alpha-dehydroxylation
      in the dUC group, but not in the pUC group.

PMID- 22369745
TI  - Three-dimensional fusion images of hepatic vasculature and bile duct used for
      preoperative simulation before hepatic surgery.
AB  - BACKGROUND/AIMS: Recent developments in radiological technology allowed
      acquisition of images with high spatial resolution that facilitate effective 3
      dimensional (3D) reconstruction of fusion images. Present study utilized 3D
      cholangiography and angiography with multi-detector-row computed tomography
      (MDCT) to acquire information regarding operative simulations. METHODOLOGY: 3D
      fusion images were evaluated in 39 patients with hepatobiliary malignancies who
      underwent surgical resections. RESULTS: An aberrant branch of segment 3 over the
      umbilical portal vein, a large hepatoma compressed the hilar vessels, an aberrant
      branch of the caudate lobe vasculature in case of metastatic liver tumor with a
      right-sided umbilical portal vein and transected biliary leakage were clearly
      observed by 3D imaging system. Four patients with intrahepatic cholangiocarcinoma
      underwent multiple biliary stent placements and adequate placement of biliary
      stents was possible. In 22 patients with extrahepatic biliary carcinomas,
      visualization of the extent of tumor invasion by 3D-fusion images was equivalent
      to conventional cholangiography. In 2 patients, adequate placement of multiple
      stents could be visualized with this system. In 2 patients who underwent
      hepatectomy, more extended cancer invasion was observed than was visualized by 3D
      fusion images. CONCLUSIONS: 3D fusion images were very useful for preoperative
      simulations in order to understand relationships between tumors and adjacent
      vasculatures.

PMID- 22369746
TI  - Predictive factors of recurrence for patients with intrahepatic
      cholangiocarcinoma after hepatectomy.
AB  - BACKGROUND/AIMS: To identify risk factors related to postoperative recurrence for
      intrahepatic cholangiocarcinoma (ICC) patients with negative resection margin.
      METHODOLOGY: A total of 64 ICC patients who underwent resection with negative
      margin at our center from 2002 to 2010 were recruited in the present study. All
      clinicopathological characteristics were assessed using univariate analyses.
      Independent risk factors were identified by Cox regression. Factors significant
      at a p<0.10 in the univariate analyses were involved in the multivariate
      analyses. The diagnostic accuracy of the identified risk factors was evaluated
      using receiver operating curve (ROC). RESULTS: The overall 1-, 3- and 5-year
      recurrence-free survival rates for patients with ICC were 63%, 32% and 27%,
      respectively. The most common site of postoperative recurrence was the liver.
      Lymph node metastasis, perineural invasion and total tumor size greater than 5 cm
      showed prognostic power in multivariate analysis. The recurrence-free survival
      rates reduced with the increasing of the number of risk factor for patients with
      ICC. CONCLUSIONS: This study suggested liver was the most common recurrence site
      and confirmed lymph node metastasis, perineural invasion and total tumor size
      greater than 5 cm may be associated with poor outcome for ICC patients with
      negative resection margin.

PMID- 22369747
TI  - Thoracoscopic esophagectomy in the prone position.
AB  - Thoracoscopic esophagectomy performed with the patient in the left lateral
      position has been occasionally reported since the 1990s, but it has not been
      established as a standard procedure. This may be because the success of this
      procedure largely depends on the technical competence of an assistant to secure
      an adequate field of view during the procedure. Thoracoscopic esophagectomy with
      the patient in the prone position has recently been introduced and has been
      consistently shown to be useful. Compared with left lateral thoracoscopic
      esophagectomy, prone thoracoscopic esophagectomy requires less assistance in
      exposing the operative field and it is relatively easy to obtain a satisfactory
      field of view. We performed prone thoracoscopic esophagectomy on 20 patients and
      were successful in achieving a wide field of view. The postoperative course was
      remarkably favorable in all patients and the procedure is considered promising
      for standard thoracoscopic esophagectomy. There are few detailed reports of this
      procedure; herein, we describe the procedure of prone thoracoscopic esophagectomy
      employed at our hospital.

PMID- 22369749
TI  - Estrogenic involvement in social learning, social recognition and pathogen
      avoidance.
AB  - Sociality comes with specific cognitive skills that allow the proper processing
      of information about others (social recognition), as well as of information
      originating from others (social learning). Because sociality and social
      interactions can also facilitate the spread of infection among individuals the
      ability to recognize and avoid pathogen threat is also essential. We review here
      various studies primarily from the rodent literature supporting estrogenic
      involvement in the regulation of social recognition, social learning (socially
      acquired food preferences and mate choice copying) and the recognition and
      avoidance of infected and potentially infected individuals. We consider both
      genomic and rapid estrogenic effects involving estrogen receptors alpha and beta,
      and G-protein coupled estrogen receptor 1, along with their interactions with
      neuropeptide systems in the processing of social stimuli and the regulation and
      expression of these various socially relevant behaviors.

PMID- 22369750
TI  - Trends of BMI and prevalence of overweight and obesity in Portugal (1995-2005): a
      systematic review.
AB  - OBJECTIVE: Locale-specific data on BMI and overweight/obesity are necessary to
      understand how the obesity epidemic is evolving in each setting. We aimed to
      describe the temporal trends of mean BMI and prevalences of overweight/obesity in
      studies that evaluated Portuguese adults and older people. DESIGN: Systematic
      review, conducted via a PubMed search up to January 2011 and independent
      reference screening and data extraction. Twenty-one eligible studies were
      identified. Data were extracted from the published reports and obtained from the
      authors of seven of the largest studies. Adjusted ecological estimates of mean
      BMI and prevalences of overweight/obesity were computed by linear regression.
      RESULTS: Between 1995 and 2005, when using data obtained from anthropometric
      measurements, overweight prevalence increased by 3.2 % and 3.5 % and obesity
      prevalence by 7.4 % and 1.3 % among women and men, respectively, while mean BMI
      did not vary meaningfully. When using self-reported information, mean BMI
      increased by 0.8 kg/m2 and 0.9 kg/m2, overweight prevalence by 3.5 % and 3.7 %
      and obesity prevalence by 5.8 % and 5.5 % among women and men, respectively.
      Results from the 20-year-old conscripts (1960-2000) showed a marked increase in
      these outcomes in the last decades. CONCLUSIONS: Our results show an important
      increase in overweight/obesity in younger ages. The trends in the indicators
      derived from self-reported data suggest an increase in awareness of the
      importance of overweight/obesity among the population.

PMID- 22369748
TI  - The neutralization sensitivity of viruses representing human immunodeficiency
      virus type 1 variants of diverse subtypes from early in infection is dependent on
      producer cell, as well as characteristics of the specific antibody and envelope
      variant.
AB  - Neutralization properties of human immunodeficiency virus (HIV-1) are often
      defined using pseudoviruses grown in transformed cells, which are not
      biologically relevant HIV-1 producer cells. Little information exists on how
      these viruses compare to viruses produced in primary lymphocytes, particularly
      for globally relevant HIV-1 strains. Therefore, replication-competent chimeras
      encoding envelope variants from the dominant HIV-1 subtypes (A, C, and D)
      obtained early after infection were generated and the neutralization properties
      explored. Pseudoviruses generated in 293T cells were the most sensitive to
      antibody neutralization. Replicating viruses generated in primary lymphocytes
      were most resistant to neutralization by plasma antibodies and most monoclonal
      antibodies (b12, 4E10, 2F5, VRC01). These differences were not associated with
      differences in envelope content. Surprisingly, the virus source did not impact
      neutralization sensitivity of most viruses to PG9. These findings suggest that
      producer cell type has a major effect on neutralization sensitivity, but in an
      antibody dependent manner.

PMID- 22369751
TI  - Preparation and rapid analysis of antibacterial silver, copper and zinc doped sol
      gel surfaces.
AB  - The colonisation of clinical and industrial surfaces with microorganisms,
      including antibiotic-resistant strains, has promoted increased research into the
      development of effective antibacterial and antifouling coatings. This study
      describes the preparation of metal nitrate (Ag, Cu, Zn) doped
      methyltriethoxysilane (MTEOS) coatings and the rapid assessment of their
      antibacterial activity using polyproylene microtitre plates. Microtitre plate
      wells were coated with different volumes of liquid sol-gel and cured under
      various conditions. Curing parameters were analysed by thermogravimetric analysis
      (TGA) and visual examination. The optimum curing conditions were determined to be
      50-70 degrees C using a volume of 200 MUl. The coated wells were challenged with
      Gram-positive and Gram-negative bacterial cultures, including biofilm-forming and
      antibiotic-resistant strains. The antibacterial activities of the metal doped sol
      gel, at equivalent concentrations, were found to have the following order:
      silver>zinc>copper. The order is due to several factors, including the increased
      presence of silver nanoparticles at the sol-gel coating surface, as determined by
      X-ray photoelectron spectroscopy, leading to higher elution rates as measured by
      inductively coupled plasma atomic emission spectroscopy (ICP-AES). The use of
      microtitre plates enabled a variety of sol-gel coatings to be screened for their
      antibacterial activity against a wide range of bacteria in a relatively short
      time. The broad-spectrum antibacterial activity of the silver doped sol-gel
      showed its potential for use as a coating for biomaterials.

PMID- 22369752
TI  - Probing aggregation and fibril formation of insulin in polyelectrolyte
      multilayers.
AB  - Ultrathin films are useful for coating materials and controlling drug delivery
      processes. Here, we explore the use of polyelectrolyte multilayers as templates
      for the formation of two-dimensional protein networks, which represent
      biocompatible and biodegradable ultrathin films. In a first step, we have studied
      the lateral aggregation and amyloid fibril formation of bovine insulin that is
      adsorbed at and confined within planar polyelectrolyte multilayers, assembled
      with poly(diallyldimethylammonium chloride) (PDDA), poly(styrenesulfonic acid)
      (PSS), and hyaluronic acid (HA). Si-PDDA-PSS-(insulin-PSS)(x) and Si-PDDA-PSS
      (insulin-HA)(x) multilayers (x=1-4) have been prepared and characterized in the
      fully hydrated state by using X-ray reflectometry, attenuated total reflection
      Fourier transform infrared spectroscopy and confocal fluorescence microscopy. The
      obtained data demonstrate a successful build-up of the insulin-polyelectrolyte
      multilayers on silicon wafers that grow strongly in thickness upon insulin
      adsorption on PSS and HA layers. The secondary structure analysis of insulin,
      based on the vibrational amide I'-band, indicates an enhanced intermolecular beta
      sheet formation within the multilayers at 70 degrees C and pD=2, i.e. at
      conditions that promote insulin amyloid fibrils rich in beta-sheet contents.
      However, insulin that is confined between two polyelectrolyte layers rather forms
      amorphous aggregates as can be inferred from confocal fluorescence images.
      Remarkably, when insulin is deposited as the top-layer, a partial conversion into
      a two-dimensional fibrillar network can be induced by adding amyloid seeds to the
      solution. Thus, the results of this study illustrate the capability of
      polyelectrolyte multilayers as templates for the growth of protein networks.

PMID- 22369753
TI  - Can technology assist teen smokers to "kick the habit"?

PMID- 22369754
TI  - Remote pharmacological preconditioning on median nerve territory increases Hsp32
      expression and attenuates ischemia-reperfusion injury in rat heart.
AB  - AIMS: The aim of this study was to test the hypothesis that remote
      pharmacological preconditioning (RPP) induced myocardial heat shock protein (Hsp)
      32 expression and attenuated the ischemia-reperfusion (I/R) injury of the heart
      in rats. MAIN METHODS: Animals were injected at the left median nerve territory
      with chloralose and urethane mixture. At different time intervals, myocardial
      Hsp32 gene expression was analyzed. Primary heart cultures were used to
      investigate the direct effect of drug mixture on Hsp32 expression. KEY FINDINGS:
      The results showed that Hsp32 was time- and dose-dependently increased by in vivo
      drug mixture treatment, but not in primary cultures. RPP significantly decreased
      the duration of arrhythmia and incidence of stony heart in rats with subsequent
      I/R injury. SIGNIFICANCE: We conclude that RPP on the left median nerve territory
      induced Hsp32 gene expression in the heart and attenuates myocardial damage
      functionally after subsequent I/R injury.

PMID- 22369755
TI  - Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial
      cells.
AB  - AIMS: To elucidate how the nicotinic acetylcholine receptors expressed on
      bronchial and oral epithelial cells targeted by the tobacco nitrosamine (4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) facilitate carcinogenic
      transformation. MAIN METHODS: Since NNK-dependent transformation can be abolished
      by the nicotinergic secreted mammalian Ly-6/urokinase plasminogen activator
      receptor related protein-1 (SLURP-1), we compared effects of NNK and recombinant
      (r)SLURP-1 on the expression of genes related to tumorigenesis in human
      immortalized bronchial and oral epithelial cell lines BEP2D and Het-1A,
      respectively. KEY FINDINGS: NNK stimulated expression of oncogenic genes,
      including MYB and PIK3CA in BEP2D, ETS1, NRAS and SRC in Het-1A, and AKT1, KIT
      and RB1 in both cell types, which could be abolished in the presence of rSLURP-1.
      Other cancer-related genes whose upregulation by NNK was abolishable by rSLURP-1
      were the growth factors EGF in BEP2D cells and HGF in Het-1A cells, and the
      transcription factors CDKN2A and STAT3 (Het-1A only). NNK also upregulated the
      anti-apoptotic BCL2 (Het-1A) and downregulated the pro-apoptotic TNF (Het-1A),
      BAX and CASP8 (BEP2D), all of which could be abolished, in part, by rSLURP-1. NNK
      decreased expression of the CTNNB1 gene encoding the intercellular adhesion
      molecule beta-catenin (BEP2D), as well as tumor suppressors CDKN3 and FOXD3 in
      BEP2D cells and SERPINB5 in Het-1A cells. These pro-oncogenic effects of NNK were
      abolished by rSLURP-1 that also upregulated RUNX3. SIGNIFICANCE: The obtained
      results identified target genes for both NNK and SLURP-1 and shed light on the
      molecular mechanism of their reciprocal effects on tumorigenic transformation of
      bronchial and oral epithelial cells.

PMID- 22369756
TI  - Global metabolomic responses of Escherichia coli to heat stress.
AB  - Microbial metabolomic analysis is essential for understanding responses of
      microorganisms to heat stress. To understand the comprehensive metabolic
      responses of Escherichia coli to continuous heat stress, we characterized the
      metabolomic variations induced by heat stress using NMR spectroscopy in
      combination with multivariate data analysis. We detected 15 amino acids, 10
      nucleotides, 9 aliphatic organic acids, 7 amines, glucose and its derivative
      glucosylglyceric acid, and methanol in the E. coli extracts. Glucosylglyceric
      acid was reported for the first time in E. coli. We found that heat stress was an
      important factor influencing the metabolic state and growth process, mainly via
      suppressing energy associated metabolism, reducing nucleotide biosynthesis,
      altering amino acid metabolism and promoting osmotic regulation. Moreover,
      metabolic perturbation was aggravated during heat stress. However, a sign of
      recovery to control levels was observed after the removal of heat stress. These
      findings enhanced our understanding of the metabolic responses of E. coli to heat
      stress and demonstrated the effectiveness of the NMR-based metabolomics approach
      to study such a complex system.

PMID- 22369757
TI  - Delayed administration of VEGF rescues spinal motor neurons from death with a
      short effective time frame in excitotoxic experimental models in vivo.
AB  - VEGF (vascular endothelial growth factor) prevents neuronal death in different
      models of ALS (amyotrophic lateral sclerosis), but few studies have addressed the
      efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical
      point when considering VEGF as a potential therapeutic target for ALS. We studied
      the capability of VEGF to protect motor neurons after an excitotoxic challenge in
      two models of spinal neurodegeneration in rats induced by AMPA (alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid) administered either chronically with
      osmotic minipumps or acutely by microdialysis. VEGF was administered through
      osmotic minipumps in the chronic model or injected intracerebroventricularly in
      the acute model, and its effects were assessed by immunohistochemical and
      histological analyses and motor performance tests. In the chronic model, VEGF
      stopped the progression of the paralysis and protected motor neurons when
      administered after AMPA before the onset of the motor symptoms, whereas no
      protection was observed when administered after the onset. VEGF was also
      protective in the acute model, but with a short time window, since the protection
      was effective when administered 1 h but not 2 h after AMPA. Our results indicate
      that while VEGF has an indubitable neuroprotective effect, its therapeutic
      potential for halting or delaying the progression of motor neuron loss in ALS
      would likely have a short effective time frame.

PMID- 22369758
TI  - Study of Staphylococcus aureus collected at slaughter from dairy cows with
      chronic mastitis.
AB  - Staphylococcus aureus is one of the most important pathogens associated with
      bovine mastitis. Recent studies have shown that Staph. aureus strains may differ
      in virulence, and in their ability to disseminate across commercial dairy herds.
      The goal of this study was to determine whether Staph. aureus isolates differed
      in their ability to colonize mammary tissue, and whether such differences could
      be related to molecular characteristics. Quarter milk and mammary tissues of 22
      cows from two dairy herds, were collected at slaughter and bacteriological
      analysis was performed. All Staph. aureus isolates were characterized by Pulsed
      Field Gel Electrophoresis (PFGE) and microarray. Overall 45 mammary quarters were
      infected and 20 Staph. aureus isolates were identified. The bacteria were mostly
      recovered from both milk and tissue of the same quarter in significantly higher
      numbers from herd A cows compared with herd B. Molecular characterization of the
      isolates showed distinct PFGE profiles for isolates from each herd. Differences
      in virulence factors between herds A and B isolates were evidenced The genes for
      enterotoxin D, J and R were present in herd A, those for G, I, N, M, O and U were
      shown in herd B, whilst both components of the leukocidin lukD/E genes were only
      carried by herd A isolates. Furthermore, all herd A isolates showed beta
      haemolysin activity, which was absent in all but one isolate from herd B.
      Therefore our data indicate that Staph. aureus isolates showing differences in
      their ability to disseminate and colonize across quarters, also have
      significantly different virulence characteristics.

PMID- 22369759
TI  - Term myometrium is characterized by increased activating epigenetic modifications
      at the progesterone receptor-A promoter.
AB  - Term human myometrial expression of progesterone receptor (PR)-A is increased
      relative to PR-B, and as PR-A is a repressor of progesterone action mediated
      through PR-B, this increase may mediate the withdrawal of progesterone action and
      precipitate the onset of labour. PR-A and PR-B expression is regulated by two
      separate promoters of the PR gene. We hypothesized that epigenetic histone
      modifications at the two promoters contribute to the labour-associated regulation
      of PR-A and PR-B expression in term myometrium. PR total, PR-B and PR-A mRNA
      levels were determined using quantitative real-time PCR, and chromatin
      immunoprecipitation was used to determine the levels of activating and repressive
      histone modifications at the PR-A and PR-B promoters in human myometrial samples
      not in labour (n = 4) and in labour (n = 4). Chromatin extracts were
      immunoprecipitated with antibodies against activating (histone H3 and H4
      acetylation and histone H3 lysine 4 trimethylation), and repressive (histone H3
      lysine 9 trimethylation, histone H3 lysine 27 trimethylation and asymmetrical
      histone H3 arginine 2 dimethylation) histone modifications. PR-A mRNA levels
      increased during labour, while PR-B mRNA levels remained constant resulting in an
      increase of PR-A/PR-B mRNA ratio, as expected. Regardless of labour status,
      significantly higher levels of the activating histone modifications were found at
      the PR-A promoter compared with the PR-B promoter (P <0.001). H3K4me3 increased
      significantly at both promoters with labour onset (P =0.001). Low levels of the
      repressive histone modifications were also present at both promoters, with no
      labour-associated changes observed. Our data indicate that the PR-A promoter is
      epigenetically marked for activation in term myometrium more extensively than the
      PR-B promoter, and that labour is associated with an increase in H3K4me3
      activating modification, consistent with the previously described increase in PR
      protein at this time.

PMID- 22369760
TI  - Second-order motion is less efficient at modulating vection strength.
AB  - Visually induced illusions of self-motion (vection) are often induced using
      constant velocity optic flow. However, adding simulated viewpoint jitter and
      oscillation to these displayscan significantly improve the vection experience
      (especially when this jitter/oscillation is orthogonal  to the constant flow
      component - Nakamura, 2010; Palmisano et al., 2008). In the present experiment,
      we found that vection was only facilitated when luminance-, but not contrast-,
      defined vertical oscillatory motion was added to the constant horizontal display
      motion (even  though observers clearly reported seeing both the oscillatory and
      constant display motions in both conditions). These findings demonstrate that the
      vection enhancement provided by simulated viewpoint oscillation is not simply
      based on the perceived display motion.

PMID- 22369761
TI  - Extravascular lung water in acute respiratory distress syndrome: potential
      clinical value, assumptions and limitations.
AB  - Extravascular lung water has been proposed as a marker of disease severity,
      response to treatment and mortality in patients with acute respiratory distress
      syndrome. Here, we discuss its potential value and limitations in clinical
      practice.

PMID- 22369762
TI  - Thermionic emission from the 2DEG assisted by image-charge-induced barrier
      lowering in AlInN/AlN/GaN heterostructures.
AB  - The effect of image charges on current transport mechanisms investigated at the
      nanoscale in Al(1-x)In(x)N/GaN heterostructures was studied. Current-voltage (I
      V) measurements were performed locally using a conductive AFM-tip as a nanoprobe
      and the conduction mechanism was modeled to explain the observed behavior. This
      model suggests that current transport is controlled by thermionic emission (TE)
      of the two-dimensional electron gas (2DEG) across the potential barrier at the
      heterointerface, where the image charges generated by the 2DEG induce a barrier
      lowering at the Al(1-x)In(x)N/GaN interface, enhancing electron transport. This
      barrier lowering depends on the 2DEG characteristics, such as 2DEG density n(2D),
      first subband energy E0 and the average distance x0 of the 2DEG from the
      interface. By fitting the experimental I-V curves with the present model the 2DEG
      density was evaluated. The obtained results were in very good agreement with the
      Hall measurements.

PMID- 22369763
TI  - Thyroid hormones in milk and blood of lactating donkeys as affected by stage of
      lactation and dietary supplementation with trace elements.
AB  - The traditional utilization of donkeys (Equus asinus) as dairy animals has
      recently attracted substantial scientific interest with regard to human
      nutrition. Donkey milk is well tolerated by infants with cows' milk allergy,
      useful in the treatment of human immune-related diseases, in the prevention of
      atherosclerosis, and in-vitro studies showed an anti-proliferative effect. Active
      3-3'-5-triiodothyronine (T3) in colostrum and milk could play different
      physiological roles, systemic and paracrine, for both the mother and the suckling
      offspring. The aim was to evaluate whether thyroid hormones (TH) concentrations
      in milk and blood of lactating donkeys change with the advancing lactation and
      whether they can be affected by dietary supplementation with several trace
      elements, some of them directly involved with TH synthesis (I), metabolism (Se)
      and action (Zn). Sixteen lactating jennies were divided into two groups (CTL and
      TE). Mixed feed for TE was added with Zn, Fe, Cu, Mn, I, Se and Co. Every 2 weeks
      milk and blood samples were collected at 11.00. Total concentrations of T3 in
      milk (T3M) and T3 and T4 in plasma (T3P and T4P) were assayed using ELISA kits,
      validated for the donkey species. T3M was not correlated with TH concentrations
      in blood, did not change with the stage of lactation, and was significantly
      higher in TE (4.09 +/- 0.07 ng/ml, mean +/- SE) than in CTL group (3.89 +/- 0.08
      ng/ml). T4P (81.8 +/- 5.2 ng/ml) and T3P (15.2 +/- 1 ng/ml) significantly changed
      with time, but were not significantly affected by dietary treatment. T3P/T4P
      ratio was significantly lower in TE group. This study indicates that in donkey
      milk the concentration of T3, a human-like bioactive compound, can be affected by
      trace elements intake.

PMID- 22369764
TI  - Evolution from a non-Fermi liquid Kondo lattice to intermediate valence behaviour
      in CeRhSn(1-x)In(x).
AB  - We present investigations of the magnetic and electric transport properties,
      specific heat, and electronic structure of the intermetallic and strongly
      correlated system of CeRhSn(1-x)In(x) compounds. The main goal of this paper is
      to determine the hybridization energy between the f electron and conduction
      electron states, V(cf), and its influence on the ground state properties of the
      system. The complementary experimental data are discussed on the basis of the
      Anderson model for a periodic Kondo lattice. CeRhSn is known as a non-Fermi
      liquid, while CeRhIn is a valence fluctuating system. We discuss the ground state
      properties of CeRhSn(1-x)In(x) and compare the results with those obtained for
      the doped Ce-based Kondo insulators.

PMID- 22369765
TI  - Short-acting P2Y12 blockade to reduce platelet dysfunction and coagulopathy
      during experimental extracorporeal circulation and hypothermia.
AB  - BACKGROUND: Extracorporeal circulation (ECC) and hypothermia are routinely used
      in cardiac surgery to maintain stable circulatory parameters and to increase the
      ischaemic tolerance of the patient. However, ECC and hypothermia cause platelet
      activation and dysfunction possibly followed by a devastating coagulopathy.
      Stimulation of the adenosinediphosphate (ADP) receptor P(2)Y(12) plays a pivotal
      role in platelet activation. This experimental study tested P(2)Y(12) receptor
      blockade as an approach to protect platelets during ECC. METHODS: Human blood was
      treated with the short-acting P(2)Y(12) blocker cangrelor (1 uM, t(1/2)<5 min) or
      the P(2)Y(12) inhibitor 2-MeSAMP (100 uM) and circulated in an ex vivo ECC model
      at normothermia (37 degrees C) and hypothermia (28 degrees C). Before and after
      circulation, markers of platelet activation and of coagulation (thrombin
      antithrombin complex generation) were analysed. During hypothermic ECC in pigs,
      the effect of reversible P(2)Y(12) blockade on platelet function was evaluated by
      cangrelor infusion (0.075 ug kg(-1) min(-1)). RESULTS: During ex vivo hypothermic
      ECC, P(2)Y(12) blockade inhibited platelet granule release (P<0.01), platelet
      granulocyte binding (P<0.05), and platelet loss (P<0.001), whereas no effects on
      platelet-ECC binding, platelet CD42balpha expression, glycoprotein IIb/IIIa
      activation, or thrombin-antithrombin complex generation were observed. During
      hypothermic ECC in pigs, cangrelor inhibited platelet-fibrinogen binding (P<0.05)
      and ADP-induced platelet aggregation (P<0.001). Platelet function was rapidly
      restored after termination of cangrelor infusion. CONCLUSIONS: P(2)Y(12) blockade
      by cangrelor prevents platelet activation during ECC and hypothermia. Owing to
      its short half-life, platelet inhibition can be well controlled, thus potentially
      reducing bleeding complications. This novel pharmacological strategy has the
      potential to reduce complications associated with ECC and hypothermia.

PMID- 22369767
TI  - Effect of pain on autonomic nervous system indices derived from
      photoplethysmography in healthy volunteers.
AB  - BACKGROUND: Photoplethysmographic pulse wave amplitude (PPGA) and heart rate (HR)
      can be used to measure cold, nociception-induced autonomic responses, or both.
      The aim of our study was to correlate the intensity of experimental pain to
      changes in physiological variables reflecting the autonomic nervous system
      response to pain. METHODS: PPGA, HR, and subjective measurements of pain
      intensity were measured in 29 healthy male volunteers during two heat stimuli (43
      degrees C and 48 degrees C) and the cold pressor test (CPT). Surgical pleth index
      (SPI), autonomic nervous system state (ANSS), and ANSS index (ANSSi) were
      calculated using PPGA and HR. RESULTS: Pain intensity scores increased on the
      average by 1.6, 3.5, and 8.1 for the 43 degrees C, 48 degrees C, and CPT stimuli,
      respectively. The pain intensity scores for all three stimuli groups were
      significantly different from each other (P<0.001). All three stimuli changed HR,
      PPGA, SPI, ANSS, and ANSSi values significantly from their respective baseline
      values (P<0.001 for all). Heat stimuli-induced pain intensity did not correlate
      with the magnitude of the respective changes in HR, PPGA, SPI, ANSS, and ANSSi.
      CPT-induced pain intensity correlated with the magnitude of the respective
      changes in HR, PPGA, SPI, ANSS, and ANSSi. PPGA, ANSSi, ANSS, and SPI
      differentiated between heat and cold stimuli-induced pain. CONCLUSIONS: All three
      thermal stimuli produced a significant change in photoplethysmograph-derived
      parameters. All photoplethysmograph-derived parameters appear to be suitable to
      study autonomic nervous system activation.

PMID- 22369766
TI  - Ventilatory responses after major surgery and high dependency care.
AB  - BACKGROUND: Disturbed breathing during sleep, with episodic upper airway
      obstruction, is frequent after major surgery. Ventilatory responses to
      hypercapnia and hypoxia during episodes of airway obstruction are difficult to
      investigate because the usual measure, that of ventilation, has been attenuated
      by the obstruction. We simulated the blood gas stimulus associated with
      obstruction to allow investigation of the responses. METHODS: To assess
      ventilatory responses, we studied 19 patients, mean age 59 (19-79), first at
      discharge from high dependency care after major abdominal surgery and then at
      surgical review, ~6 weeks later. Exhaled gas was analysed and inspired gas
      adjusted to simulate changes that would occur during airway obstruction. Changes
      in ventilation were measured over the following 45-70 s. Studies were done from
      air breathing if possible, and also from an increased inspired oxygen
      concentration. RESULTS: During simulated obstruction, hypercapnia developed
      similarly in all the test conditions. Arterial oxygen saturation decreased
      significantly more rapidly when the test was started from air breathing. The mean
      ventilatory response was 5.8 litre min(-2) starting from air breathing and 4.5
      litre min(-2) with oxygen breathing. The values 6 weeks later were 5.9 and 4.3
      litre min(-2), respectively (P=0.05, analysis of variance). There was no
      statistical difference between the responses starting from air and those on
      oxygen. CONCLUSIONS: After major surgery, ventilatory responses to hypercapnia
      and hypoxaemia associated with airway obstruction are small and do not improve
      after 6 weeks. With air breathing, arterial oxygen desaturation during simulated
      rebreathing is substantial.

PMID- 22369768
TI  - Putative TRP channel antagonists, SKF 96365, flufenamic acid and 2-APB, are non
      competitive antagonists at recombinant human alpha1beta2gamma2 GABA(A) receptors.
AB  - Although transient receptor potential (TRP) channel biology research has expanded
      rapidly in recent years, the field is hampered by the widely held, but relatively
      poorly investigated, belief that most of the pharmacological tools used to
      investigate TRP channel function may not be particularly selective for their
      intended targets. The objective of this study was therefore to determine if this
      was indeed the case by systematically evaluating the effects of three routinely
      used putative TRP channel antagonists, SKF 96365, flufenamic acid (FF) and 2
      aminoethoxydiphenyl borate (2-APB) against one of the most widely expressed CNS
      receptor subtypes CNS, the human alpha1beta2gamma2 GABA(A) receptor. Using whole
      cell patch-clamp recording to record responses to rapidly applied GABA in the
      absence and presence of the three putative antagonists in turn we found that SKF
      96365 (1-100 MUM) and FF (1-100 MUM) significantly inhibited GABA responses of
      recombinant human alpha1beta2gamma2 GABA(A) receptor stably expressed in HEK293
      cells with IC(50) values of 13.4 +/- 5.1 and 1.9 +/- 1.4 MUM, respectively,
      suppressing the maximal response to GABA at all concentrations used in a manner
      consistent with a non-competitive mode of action. SKF 96365 and FF also both
      significantly reduced desensitisation and prolonged the deactivation kinetics of
      the receptors to GABA (1mM; P<0.05). 2-APB (10-1000 MUM) also inhibited responses
      to GABA at all concentrations used with an IC(50) value of 16.7 +/- 5.4 MUM (n=3
      5) but had no significant effect on the activation, desensitisation or
      deactivation kinetics of the GABA responses. Taken together this investigation
      revealed that these widely utilised TRP channel antagonists display significant
      'off-target' effects at concentrations that are routinely used for the study of
      TRP channel function in numerous biological systems and as such, data which is
      obtained utilising these compounds should be interpreted with caution.

PMID- 22369769
TI  - Theoretical studies on the related properties of Co(III) polypyridyl complexes
      interacting with DNA.
AB  - Theoretical studies on the related properties of Co(III) polypyridyl complexes
      [Co(phen)(2)L](3+) (L: dppz = dipyrido[3,2-a:2',3'-c]phenazine; phen = 1,10
      phenanthroline; dione = 1,10-phenanthroline-5,6-diketone) 1-3 interacting with
      DNA, including the DNA-binding, DNA-photocleavage and spectral properties, have
      been carried out. First, the full geometry-optimizations of these three complexes
      in their ground states were carried out in aqueous solution. The optimized
      structures of these three complexes were docked into DNA-base-pairs using the
      Dock6.0 program. Secondly, the binding modes of complexes 1-3 were revealed in
      detail and the trend in DNA-binding affinities was reasonably explained. Thirdly,
      the electronic absorption and emission spectra of docking model of the optimal
      complex 1 were calculated and simulated. The experimental intense absorption and
      emission bands of Co(SH) complex 1 in the presence of DNA were explained in
      detail, in particular, the reason why the emission spectra of complex 1 in the
      presence of DNA are greatly stronger than those in the absence of DNA was
      theoretically elucidated. Finally, the DNA-photocleavage essential of complexes
      was explored and the DNA photocleavage efficiencies (phi), i.e.,
      phi(1)>phi(2)>phi(3), was also reasonably explained.

PMID- 22369770
TI  - Lathyrus cicera copper amine oxidase reactions with tryptamine.
AB  - Lathyrus cicera copper amine oxidase (LCAO) rapidly formed the typical Cu(I)-TPQ
      semiquinone UV-visible spectrum, identical to that formed by other substrates,
      upon O(2) exhaustion by turnover with excess tryptamine. A new band at 630 nm
      formed more slowly, with intensity dependent on aldehyde and H(2)O(2)
      concentrations. On prolonged incubation, all bands decayed in parallel, together
      with loss of enzymatic activity. The blue color disappeared on addition of KCN, a
      Cu(I) stabilizing agent, while the intensity of the radical visible bands
      increased. This shows that the 630 nm absorbing species is a Cu(II) derivative,
      as confirmed by the unchanged intensity of the EPR spectrum of the frozen blue
      solution from that of the native protein. Rapid kinetics experiments showed that
      this species derives from a reduced form of the protein, plus aldehyde and
      H(2)O(2) and that it is not in dynamic equilibrium with the radical. Given the
      similar population of the semiquinone radical with all substrates, it is possible
      that the reaction with aldehyde and H(2)O(2) occurs in all cases although
      substrates lacking the indole group only produce the Cu(I)-semiquinone band. The
      radical participation to the catalytic activity is demonstrated by the
      observation that its relative population (controlled by the pH) parallels changes
      in the reoxidation rate constant, while the 630 nm absorbing species is implied
      in the inactivation process, which depends on H(2)O(2) and aldehyde
      concentration. The results of the paper are consistent with half-of-the-site
      reactivity, i.e. the two subunits of LCAO are kinetically and spectroscopically
      distinct from each other.

PMID- 22369771
TI  - Novel methylene modified cyclohexyl ethylenediamine-N,N'-diacetate ligands and
      their platinum(IV) complexes. Influence on biological activity.
AB  - This paper focuses on the synthesis, characterization and biological activity of
      new N,N'-methylene modified cyclohexyl ethylenediamine-N,N'-diacetate (edda)-type
      ligands and their Pt(IV) complexes. Both the ligands and complexes were
      characterized by infrared, UV-vis, ESI-MS, 1D ((1)H, (13)C, (195)Pt) and 2D
      (COSY, HSQC, HMBC) NMR spectroscopy and elemental analysis. The possible
      correlation between the reduction potentials and the cytotoxicity of the
      complexes was examined. The potential antitumoral activity of all compounds was
      tested in vitro on human melanoma A375, human glioblastoma U251, human prostate
      cancer PC3, human colon cancer HCT116, mouse melanoma B16 and mouse colon cancer
      CT26CL25 cells, as well as primary fibroblasts and keratinocytes. The results
      obtained revealed strong antitumor potential of the newly synthesized drugs with
      preserved efficacy against cisplatin resistant lines and less toxicity towards
      nonmalignant counterparts. The mechanism found to be responsible for the observed
      tumoricidal action of each synthesized compound was induction of apoptosis
      generally accompanied with caspase activation. Taken together, the effective
      response to the treatment of a wide range of different cell lines, including
      cisplatin resistant subclones, as well as induction of apoptosis, as the
      mechanism suggested to be the most desirable way of eliminating malignant cells,
      represents a great advantage of this novel group of drugs in comparison to other
      members in this metallo-drug family.

PMID- 22369773
TI  - Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search of
      a simple yet effective cryopreservation protocol.
AB  - OBJECTIVE: To investigate whether solid-surface vitrification (SSV) is an
      effective cryopreservation strategy regarding the integrity and function of
      prepubertal mouse testicular tissue. DESIGN: Prospective experimental study.
      SETTING: Academic research unit. ANIMAL(S): Mice. INTERVENTION(S): Testicular
      tissue from 5- to 10-day-old GFP(+) mice was cryopreserved with the use of a
      conventional uncontrolled slow freezing (USF) technique and SSV before
      intratesticular grafting in busulfan-treated GFP(-) mice. MAIN OUTCOME
      MEASURE(S): Ultrastructural cryoinjury to spermatogonial stem cells (SSCs) and
      somatic cells was assessed by electron microscopy. Tubular structure was
      evaluated by histology, and graft survival and spermatogenic recovery by
      immunohistochemistry. RESULT(S): The tubular morphology and the proportion of
      ultrastructural cryodamage were similar between vitrified and slow-frozen
      testicular fragments. Allografting of tissue after both USF and SSV resulted in a
      recovery of spermatogenesis similar to fresh samples. CONCLUSION(S): SSV resulted
      in success rates similar to USF in maintaining testicular cell ultrastructure,
      tubular morphology, and tissue function. These data provide further evidence that
      vitrification, being an inexpensive and simple technique, can be considered as an
      alternative for cryopreservation of prepubertal testicular tissue.

PMID- 22369774
TI  - A novel luteinizing hormone/chorionic gonadotropin receptor mutation associated
      with amenorrhea, low oocyte yield, and recurrent pregnancy loss.
AB  - OBJECTIVE: To study the cause for poor oocyte yield, amenorrhea, and recurrent
      pregnancy loss in a patient undergoing IVF. DESIGN: Case report. SETTING:
      University-affiliated private IVF clinic. PATIENT(S): A 33-year-old woman with
      amenorrhea, recurrent ovarian cyst formation, poor oocyte yield, and repeated
      chemical pregnancies after IVF treatments. INTERVENTION(S): The hCG stimulation
      test and luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene
      sequencing. MAIN OUTCOME MEASURE(S): The presence of LHCGR gene mutations.
      RESULT(S): The patient had a markedly abrogated androgen response to 10,000 IU of
      hCG. A novel heterozygous inactivating mutation in exon 1 of the LHCGR gene was
      detected. This mutation was superimposed on a common LHCGR polymorphism.
      CONCLUSION(S): This novel mutation may provide a potential genetic mechanism for
      the poor oocyte recovery in some IVF cases. It is the first example of a
      heterozygous inactivating mutation in the LHCGR gene.

PMID- 22369772
TI  - Alfalfa forage digestibility, quality and yield under future climate change
      scenarios vary with Sinorhizobium meliloti strain.
AB  - Elevated CO(2) may decrease alfalfa forage quality and in vitro digestibility
      through a drop in crude protein and an enhancement of fibre content. The aim of
      the present study was to analyse the effect of elevated CO(2), elevated
      temperature and Sinorhizobium meliloti strains (102F78, 102F34 and 1032 GMI) on
      alfalfa yield, forage quality and in vitro dry matter digestibility. This
      objective is in line with the selection of S. meliloti strains in order to
      maintain high forage yield and quality under future climate conditions. Plants
      inoculated with the 102F34 strain showed more DM production than those inoculated
      with 1032GMI; however, these strains did not show significant differences with
      102F78 plants. Neutral or acid detergent fibres were not enhanced in plants
      inoculated with the 102F34 strain under elevated CO(2) or temperature and hence,
      in vitro dry matter digestibility was unaffected. Crude protein content, an
      indicator of forage quality, was negatively related to shoot yield. Plants
      inoculated with 102F78 showed a similar shoot yield to those inoculated with
      102F34, but had higher crude protein content at elevated CO(2) and temperature.
      Under these climate change conditions, 102F78 inoculated plants produced higher
      quality forage. However, the higher digestibility of plants inoculated with the
      102F34 strain under any CO(2) or temperature conditions makes them more suitable
      for growing under climate change conditions. In general, elevated CO(2) in
      combination with high temperature (Climate Change scenario) reduced IVDMD and CP
      content and enhanced fibre content, which means that animal production will be
      negatively affected.

PMID- 22369775
TI  - Arachidonic acid regulation of the cytosolic phospholipase A
      2alpha/cyclooxygenase-2 pathway in mouse endometrial stromal cells.
AB  - OBJECTIVE: To investigate the role of arachidonic acid (AA) in mouse endometrial
      stromal cells. DESIGN: Experimental animal study. SETTING: University research
      laboratory. ANIMAL(S): Sexually mature female CD1-strain mice. INTERVENTION(S):
      Primary culture of endometrial stromal cells. MAIN OUTCOME MEASURE(S): Western
      blot and real-time polymerase chain reaction for gene expression and/or
      phosphorylation analysis. Luciferase assay for Cox-2 promoter analysis.
      RESULT(S): AA-derived prostaglandins play important roles during embryo
      implantation and decidualization. However, the function of AA itself in
      reproduction is largely unknown. In this study, exogenous AA stimulated
      cPLA(2alpha) phosphorylation and COX-2 expression, mainly through ERK1/2 in mouse
      endometrial stromal cells, and p38 inhibitor modestly inhibited cPLA(2alpha)
      phosphorylation induced by AA. The induction of COX-2 by AA was diminished by
      short interfering RNA against C/EBPbeta and inhibitory C/EBPbeta (LIP). C/EBPbeta
      binding site at -872--864 of Cox-2 promoter contributes to Cox-2 promoter
      activation induced by C/EBPbeta transfection. The expression of C/EBPbeta protein
      induced by AA was inhibited by p38 inhibitor, and the phosphorylation of
      C/EBPbeta induced by AA was inhibited by p38 inhibitor and ERK1/2 inhibitor. A
      nonmetabolized analogue of AA (ETYA) also enhanced cPLA(2alpha) phosphorylation
      and COX-2 expression. The activation of cPLA(2alpha)/COX-2 by AA was not
      inhibited by COX inhibitor indomethacin. CONCLUSION(S): AA can induce
      cPLA(2alpha)/COX-2 pathway activation in mouse endometrial stromal cells.

PMID- 22369777
TI  - Autopsy discoveries of death from malaria.
AB  - Malaria inflicts a huge health care burden in terms of mortality and morbidity
      worldwide. There has been evidence in the literature where many
      unexpected/unexplained deaths turned out to be related to malaria on autopsy. The
      aim of this study is to review autopsy diagnosed malaria related deaths in the
      literature with due stress to its biologic and forensic aspects. A meticulous
      literature search was performed for "sudden malaria death", "malaria death
      postmortem diagnosis" and "unexplained death malaria" across PubMed, SCOPUS,
      Cochrane Database of Systematic Reviews, Allied and Complementary Medicine,
      British Nursing Index, CINAHL, EMBASE, Ovid-MEDLINE and Google Scholar. All the
      literature was thoroughly reviewed and analyzed with reference to the type of
      study, location, travel history, age, gender, circumstance of death, method of
      diagnosis, species involved, chemoprophylaxis usage and take home message from
      the particular study. Plasmodium falciparum was responsible in most of the cases.
      The symptoms mimicked influenza in most of the case reports. Travel to endemic
      areas was common to most of the victims. The travelers were from all over the
      world including USA, France, Switzerland, Spain, Portugal, Germany and Asia
      (China and Japan). Vascular congestion with the presence of malarial pigment
      laden RBCs in capillaries of various organs was the major histopathology finding.
      Such lesions were found in the brains of all subjects (100%), liver of 78% of the
      cases, spleen in 67%, lungs in 56% and myocardium in 43% of the cases. Peripheral
      smear and rapid diagnostic test was of great aid to the autopsy in many cases.
      PCR was used for diagnosis as well as exclusion of possibility of co-infection
      with other species in case of Plasmodium knowlesi related death. The postmortem
      and histopathology findings in this case were similar to P. falciparum except for
      the fact that brain sections were negative for intracellular adhesion molecule-1.
      Chemoprophylaxis was not taken by the victims except for two in whom history of
      chloroquine based chemoprophylaxis was mentioned. Given the worldwide prevalence
      of the disease, increasing international travel and rapidly developing drug
      resistance, malaria will continue to be an important disease and should be
      considered in all cases of unexpected deaths particularly in malaria endemic
      regions or in presence of travel history to endemic regions.

PMID- 22369776
TI  - Rectal wall hemorrhage in hanging autopsy cases.
AB  - The aim of our study was to analyze hemorrhagic lesions of the rectal wall in
      hanging autopsy cases. All autopsy reports regarding hanging from January 1st,
      2008 to December 31st, 2010 were retrospectively reviewed. One hundred and two
      hanging cases were selected out of 1379 autopsy cases. Rectal wall hemorrhage was
      found in about 4% of the cases (n=4). Two of these 4 cases (50%) were associated
      with bowel wall hemorrhage, suggesting a similar possible etiology by abdominal
      congestion during the agonal phase. Another etiology could be an hemorrhagic
      lividity in the rectum. As it is not possible to determine with certainty the
      etiology, even with the use of histology, the detection of rectal wall hemorrhage
      cannot be used as another sign of vital hanging. Such rectum changes raise the
      possibility of sexual assault. Forensic pathologists should be aware of such an
      occurrence and avoid potential harmful misinterpretation.

PMID- 22369780
TI  - The bovine genomic DNA sequence data reveal three IGHV subgroups, only one of
      which is functionally expressed.
AB  - A comprehensive analysis of cattle shotgun sequencing data reveals 36
      immunoglobulin heavy chain variable genes. The previously described bovine
      subgroup IGHV1 contains 10 functional genes with a conserved promoter including
      the consensus octamer and several other transcription factor binding sites,
      intact exons and matching cDNA sequences. Subgroups IGHV2 and IGHV3 consist
      entirely of pseudogenes. Thus, the bovine germline IGHV repertoire is very
      limited. The IGHV genes are distributed in mammalian clans I and II, while no
      clan III genes were detected. Clan-specific PCR of genomic DNA from cattle,
      sheep, Eurasian elk, white-tailed deer, pig and dolphin indicates highly dynamic
      evolution of IGHV gene usage within Cetartiodactyla. The bovine germline IGHV
      repertoire was probably generated by recent duplications of an IGHV1-IGHV2
      homology unit. Immunoglobulin heavy chain genes are largely incorrectly assembled
      in the current cattle genome versions Btau_4.2 and UMD_3.1. FISH experiments
      confirm an IGHV locus close to terminus of BTA21.

PMID- 22369779
TI  - Evolutionary origin of beta-defensins.
AB  - beta-Defensins are a group of vertebrate-specific antimicrobial peptides (AMPs)
      with microbicidal and immune regulatory functions. In spite of their conservation
      across the vertebrate lineage ranging from bony fish to human, the evolutionary
      origin of these molecules remains unsolved. We addressed this issue by comparing
      three-dimensional (3D) structure and genomic organization of beta-defensins with
      those of big defensins, a family of invertebrate-derived beta-defensin-related
      peptides with two distinct structural and functional domains. beta-Defensins and
      the carboxyl-terminal domain of big defensins adopt a conserved beta-sheet
      topology stabilized by three identical disulfide bridges. Genomic organization
      analysis revealed that the defensin domain of these two classes of molecules is
      encoded by a single exon with a positionally conserved phase-1 intron in its
      upstream. The genomic and 3D structural conservation provides convincing evidence
      for their evolutionary relationship, in which beta-defensins emerged from an
      ancestral big defensin through exon shuffling or intronization of exonic
      sequences. The phylogenetic distribution of big defensins in Arthropoda, Mollusca
      and Cephalochordata suggests an early origin of the beta-defensin domain, which
      can be traced to the common ancestor of bilateral metazoans.

PMID- 22369778
TI  - Cardiac CT in women: clinical application and considerations.
AB  - Cardiac computed tomography (CT) has special considerations and applications in
      women for the evaluation of coronary heart disease (CHD). Unique aspects of
      cardiovascular disease (CVD) in women include atypical symptoms and a later
      presentation of CHD. Disparities exist in mortality trends of CVD between men and
      women along with a lack of patient awareness of CVD as a significant cause of
      mortality for women. Differences have also become evident among plaque
      characteristics between the 2 sexes, with a relative increased prevalence of
      noncalcified plaque in women. Traditional risk prediction models, such as the
      Framingham Risk Score (FRS), have limitations in this population. Coronary
      calcium scanning contributes significantly to the accuracy of CHD detection on
      top of traditional CV risk factors in asymptomatic women. Coronary CT angiography
      has proven accurate for the diagnosis of significant CHD as well as cost
      effective in the evaluation of symptomatic women. The safety issue of radiation
      exposure with cardiac CT warrants special consideration for women. Concern for
      radiation-related cancer risks and organ-specific dose delivered to the breast is
      being addressed by radiation-reducing techniques. Future technologic advances in
      CT may allow for simultaneous screening for CHD and other disease processes, such
      as osteoporosis, breast cancer, and visceral adiposity in one routine test.

PMID- 22369781
TI  - Long-chain fatty acids and inflammation.
AB  - Inflammation plays a key role in many common conditions and diseases. Fatty acids
      can influence inflammation through a variety of mechanisms acting from the
      membrane to the nucleus. They act through cell surface and intracellular
      receptors that control inflammatory cell signalling and gene expression patterns.
      Modifications of inflammatory cell membrane fatty acid composition can modify
      membrane fluidity, lipid raft formation and cell signalling leading to altered
      gene expression and can alter the pattern of lipid and peptide mediator
      production. Cells involved in the inflammatory response usually contain a
      relatively high proportion of the n-6 fatty acid arachidonic acid in their
      membrane phospholipids. Eicosanoids produced from arachidonic acid have well
      recognised roles in inflammation. Oral administration of the marine n-3 fatty
      acids EPA and DHA increases the contents of EPA and DHA in the membranes of cells
      involved in inflammation. This is accompanied by a decrease in the amount of
      arachidonic acid present. EPA is a substrate for eicosanoid synthesis and these
      are often less potent than those produced from arachidonic acid. EPA gives rise
      to E-series resolvins and DHA gives rise to D-series resolvins and protectins.
      Resolvins and protectins are anti-inflammatory and inflammation resolving. Thus,
      the exposure of inflammatory cells to different types of fatty acids can
      influence their function and so has the potential to modify inflammatory
      processes.

PMID- 22369783
TI  - Many-electron scattering applied to atomic point contacts.
AB  - Electron transport in a strong coupling regime is investigated by applying the
      many-electron correlated scattering (MECS) method to an atomic point contact
      model. Comparing the theoretical calculations to the quantum of conductance
      obtained experimentally for these systems allows for the error associated with
      the numerical implementation of the MECS method to be estimated and attributed to
      different components of the calculations. Errors associated with implementing the
      scattering boundary conditions and determination of the applied voltage in a
      finite explicit electrode model are assessed, and as well the impact on the basis
      set description on predicting the conductance is examined in this weakly
      correlated limit. The MECS calculation for the atomic point contact results in a
      conductance of 0.6G(0), in reasonable agreement with measurements for gold point
      contacts where approximately the conductance quantum G(0) is obtained. The
      analysis indicates the error attributable to numerical approximations and the
      explicit electrode model introduced in the calculations should not exceed 40% of
      the total conductance, whereas the effect of electron-electron correlations, even
      in this weakly correlated regime, can result in as much as a 30% change in the
      predicted conductance.

PMID- 22369782
TI  - Visible light induced photocatalytic reduction of Cr(VI) over polymer-sensitized
      TiO2 and its synergism with phenol oxidation.
AB  - In this study, both Cr(VI) reduction and phenol oxidation induced by polymer
      sensitized TiO(2) were investigated under visible light. Study of the reaction
      mechanism indicated that poly(fluorene-co-thiophene) (PFT) acted as a
      semiconductor and was by itself able to reduce Cr(VI) under visible light
      irradiation. When coupled with TiO(2), PFT served not only as the electron donor
      for Cr(VI) reduction, but also as a sensitizer. Upon irradiation by visible
      light, electrons in the sensitizing PFT polymer are excited and are transferred
      to the conduction band of TiO(2). PFT-catalyzed reduction of Cr(VI) was
      significantly promoted by the presence of phenol, and synergism between Cr(VI)
      reduction and phenol degradation was demonstrated both by analysis of the FT-IR
      spectrum of PFT/TiO(2) and by measuring the effect of repeated use of PFT/TiO(2)
      on its photocatalytic efficiency. The results provide a cost-effective method to
      remove organic and inorganic pollutants simultaneously in the complex wastewater.

PMID- 22369784
TI  - Olesoxime delays muscle denervation, astrogliosis, microglial activation and
      motoneuron death in an ALS mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. The
      pathology is mimicked to a striking degree in transgenic mice carrying familial
      ALS-linked SOD1 gene mutations. Olesoxime (TRO19622), a novel neuroprotective and
      reparative compound identified in a high-throughput screen based on motoneuron
      (MN) survival, delays disease onset and improves survival in mutant SOD1(G93A)
      mice, a model for ALS. The present study further analyses the cellular basis for
      the protection provided by olesoxime at the neuromuscular junctions (NMJ) and the
      spinal cord. Studies were carried out at two disease stages, 60 days,
      presymptomatic and 104 days, symptomatic. Cohorts of wild type and SOD1(G93A)
      mice were randomized to receive olesoxime-charged food pellets or normal diet
      from day 21 onward. Analysis showed that olesoxime initially reduced denervation
      from 60 to 30% compared to SOD1(G93A) mice fed with control food pellets while at
      the symptomatic stage only a few NMJs were still preserved. Immunostaining of
      cryostat sections of the lumbar spinal cord with VAChT to visualize MNs, GFAP for
      astrocytes and Iba1 for microglial cells showed that olesoxime strongly reduced
      astrogliosis and microglial activation and prevented MN loss. These studies
      suggest that olesoxime exerts its protective effect on multiple cell types
      implicated in the disease process in SOD1(G93A) mice, slowing down muscle
      denervation, astrogliosis, microglial activation and MN death. A Phase 3 clinical
      study in ALS patients will determine whether olesoxime could be beneficial for
      the treatment of ALS.

PMID- 22369785
TI  - Sex and temporally-dependent effects of methamphetamine toxicity on dopamine
      markers and signaling pathways.
AB  - Methamphetamine induces a greater neurodegenerative effect in male versus female
      mice. In order to investigate this sex difference we studied the involvement of
      Akt and extracellular signal-regulated kinase (ERK1/2) in methamphetamine
      toxicity as a function of time post-treatment (30 min, 1 and 3 days).
      Methamphetamine-induced decreases in dopamine concentrations and dopamine
      transporter (DAT) specific binding in the medial striatum were similar in female
      and male mice when evaluated 1 day post-methamphetamine (40 mg/kg). At 3 days
      post-methamphetamine, striatal dopamine concentration and DAT specific binding
      continued to decline in males, whereas females showed a recovery with increases
      in dopamine content and DAT specific binding in medial striatum at day 3 versus
      day 1 post-methamphetamine. The reduction in striatal vesicular monoamine
      transporter 2 specific binding observed at 1 and 3 days post-methamphetamine
      showed neither a sex- nor temporal-dependent effect. Under the present
      experimental conditions, methamphetamine treatments had modest effects on
      dopamine markers measured in the substantia nigra. Proteins assessed by Western
      blots showed similar reductions in both female and male mice for DAT proteins at
      1 and 3 days post-methamphetamine. An increase in the phosphorylation of striatal
      Akt (after 1 day), glycogen synthase kinase 3beta (at 1 and 3 days) and ERK1/2
      (30 min post-methamphetamine) was only observed in females. Striatal glial
      fibrillary acidic protein levels were augmented in both females and males at 3
      days post-methamphetamine. These results reveal some of the sex- and temporally
      dependent effects of methamphetamine toxicity on dopaminergic markers and suggest
      some of the signaling pathways associated with these responses.

PMID- 22369786
TI  - Hypothalamic neuropeptides and the regulation of appetite.
AB  - Neuropeptides released by hypothalamic neurons play a major role in the
      regulation of feeding, acting both within the hypothalamus, and at other appetite
      regulating centres throughout the brain. Where classical neurotransmitters signal
      only within synapses, neuropeptides diffuse over greater distances affecting both
      nearby and distant neurons expressing the relevant receptors, which are often
      extrasynaptic. As well as triggering a behavioural output, neuropeptides also act
      as neuromodulators: altering the response of neurons to both neurotransmitters
      and circulating signals of nutrient status. The mechanisms of action of
      hypothalamic neuropeptides with established roles in feeding, including melanin
      concentrating hormone (MCH), the orexins, alpha-melanocyte stimulating hormone
      (alpha-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin,
      are reviewed in this article, with emphasis laid on both their effects on
      appetite regulating centres throughout the brain, and on examining the evidence
      for their physiological roles. In addition, evidence for the involvement of
      several putative appetite regulating hypothalamic neuropeptides is assessed
      including, ghrelin, cocaine and amphetamine-regulated transcript (CART),
      neuropeptide W and the galanin-like peptides. This article is part of a Special
      Issue entitled 'Central control of Food Intake'.

PMID- 22369788
TI  - Association of tumor necrosis factor-alpha gene promoter polymorphisms (-308G/A, 
      238G/A) with recurrent spontaneous abortion: a meta-analysis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphisms (-308G/A, 
      238G/A) have been associated with increased recurrent spontaneous abortion (RSA)
      risk, but the results of published articles are controversial. Hence, a meta
      analysis was performed to assess the effect of TNF-alpha -308G/A, -238G/A
      polymorphisms on RSA risk. Heterogeneity testing and sensitivity analysis were
      performed using RevMan 5.0 software. Publication bias was assessed by the funnel
      plot method and modified Egger's linear regression test. In 12 studies for the
      TNF-alpha -308G/A polymorphism, the summary odds ratio (OR) with the
      corresponding 95% confidence interval (95% CI) was 1.04 (95% CI: 0.86, 1.26)
      under a fixed-effect model in the overall population. In 5 studies for the TNF
      alpha -238G/A polymorphism, the summary OR with the corresponding 95% CI was 1.11
      (95% CI: 0.60, 2.03) under a random-effect model in the overall population. We
      could not identify the sources of heterogeneity for TNF-alpha -238G/A. In
      addition, no evidence of publication bias was detected. The results of this meta
      analysis indicate that TNF-alpha -308G/A, -238G/A polymorphisms are not
      significantly associated with the risk of RSA in the overall population. However,
      more convincing evidence is required to draw a solid conclusion on the relation
      between the TNF-alpha -238G/A polymorphism and the risk of RSA.

PMID- 22369787
TI  - Noradrenergic antidepressant responses to desipramine in vivo are reciprocally
      regulated by arrestin3 and spinophilin.
AB  - Many antidepressant drugs, including the tricyclic antidepressant desipramine
      (DMI), are broadly understood to function by modulating central noradrenergic
      neurotransmission. alpha(2) adrenergic receptors (alpha(2)ARs) are key regulators
      of the noradrenergic system, and previous work has implicated alpha(2)ARs in
      mediating the antidepressant activity of DMI in the rodent forced swim test
      (FST). However, little is known about intracellular regulators of antidepressant
      drug action. alpha(2)AR function is tightly regulated by its intracellular
      interacting partners arrestin and the dendritic protein spinophilin. We have
      previously established the competitive and reciprocal nature of these interacting
      proteins at the alpha(2)AR in the context of classic agonist effects, and have
      shown DMI to be a direct arrestin-biased ligand at the receptor. In the present
      study, we report that mice deficient in the alpha(2A)AR subtype lack DMI-induced
      antidepressant behavioral effects in the FST. As well, mice deficient in
      arrestin3 lack antidepressant response to DMI, while spinophilin-null mice have
      enhanced antidepressant response to DMI compared with wild-type controls,
      indicating that this alpha(2A)AR-mediated response is reciprocally regulated by
      arrestin and spinophilin. The characteristic of alpha(2A)AR-dependence and
      arrestin3 involvement was shared by the antidepressant effect of the classic
      alpha(2)AR agonist clonidine but not the non-tricyclic norepinephrine reuptake
      inhibitor reboxetine, supporting a model whereby DMI exerts its antidepressant
      effect through direct engagement of the alpha(2A)AR and arrestin3. Our results
      implicate arrestin- and spinophilin-mediated regulation of the alpha(2A)AR in the
      pharmacology of the noradrenergic antidepressant DMI, and suggest that
      manipulation of this mode of receptor regulation may represent a novel and viable
      therapeutic strategy.

PMID- 22369789
TI  - The influence of post-growth annealing on the optical properties of InAs quantum
      dot chains grown on pre-patterned GaAs(100).
AB  - We report on the effect of post-growth thermal annealing of [011]- ,[011(-)]-,
      and [010]-oriented quantum dot chains grown by molecular beam epitaxy on
      GaAs(100) substrates patterned by UV-nanoimprint lithography. We show that the
      quantum dot chains experience a blueshift of the photoluminescence energy,
      spectral narrowing, and a reduction of the intersubband energy separation during
      annealing. The photoluminescence blueshift is more rapid for the quantum dot
      chains than for self-assembled quantum dots that were used as a reference.
      Furthermore, we studied polarization resolved photoluminescence and observed that
      annealing reduces the intrinsic optical anisotropy of the quantum dot chains and
      the self-assembled quantum dots.

PMID- 22369790
TI  - Open science versus commercialization: a modern research conflict?
AB  - BACKGROUND: Efforts to improve research outcomes have resulted in genomic
      researchers being confronted with complex and seemingly contradictory
      instructions about how to perform their tasks. Over the past decade, there has
      been increasing pressure on university researchers to commercialize their work.
      Concurrently, they are encouraged to collaborate, share data and disseminate new
      knowledge quickly (that is, to adopt an open science model) in order to foster
      scientific progress, meet humanitarian goals, and to maximize the impact of their
      research. DISCUSSION: We present selected guidelines from three countries
      (Canada, United States, and United Kingdom) situated at the forefront of genomics
      to illustrate this potential policy conflict. Examining the innovation ecosystem
      and the messages conveyed by the different policies surveyed, we further
      investigate the inconsistencies between open science and commercialization
      policies. SUMMARY: Commercialization and open science are not necessarily
      irreconcilable and could instead be envisioned as complementary elements of a
      more holistic innovation framework. Given the exploratory nature of our study, we
      wish to point out the need to gather additional evidence on the coexistence of
      open science and commercialization policies and on its impact, both positive and
      negative, on genomics academic research.

PMID- 22369792
TI  - Commotio cordis.

PMID- 22369793
TI  - Renal artery pseudoaneurysm resulting from blunt trauma.

PMID- 22369791
TI  - Factors associated with allergen sensitizations in patients with asthma and/or
      rhinitis in China.
AB  - BACKGROUND: Allergen sensitization is influenced by genetic and environmental
      factors; however, the factors related to sensitizations in patients with rhinitis
      and asthma in China are largely unknown. This study investigated the factors
      associated with allergen sensitizations  in patients with asthma and rhinitis in
      China. METHODS: A cross-sectional survey was performed in 6304 patients with
      asthma and/or rhinitis from four regions of China. Patients completed a
      standardized questionnaire related to respiratory and allergic symptoms, family
      history  of allergic diseases, smoking history, environmental exposure, and
      eating behaviors. They underwent skin-prick tests (SPTs) with 13 common
      aeroallergens. Blood samples were collected from 2268 of patients for specific
      IgE (sIgE) measurements against 16 common aeroallergens. RESULTS: Patients with
      both asthma and rhinitis had higher prevalence of SPT and sIgE positivity to most
      allergens than those with asthma or rhinitis alone (p < 0.0001). Male gender,
      family history of allergic rhinitis, air-conditioner usage, sleeping on a
      mattress, and frequently eating meat  were associated with increased risk of SPT
      and sIgE positivity. Using air-conditioner and sleeping on a mattress were
      further found to be associated with sIgE positivity to mites and molds. However,
      increased age and fish, fruit, and raw vegetable intake decreased the risk of SPT
      and sIgE  positivity. CONCLUSION: Family history of allergic rhinitis, male
      gender, using an air conditioner, sleeping on a mattress, and frequent meat
      consumption are risk factors for allergen sensitizations, whereas increased age
      and frequent fish, fruit, and raw vegetable consumption  may protect patients
      with asthma and/or rhinitis from developing sensitizations in China.

PMID- 22369794
TI  - Unretrieved gallstone mimicking an intra-abdominal soft tissue mass.

PMID- 22369795
TI  - Perianal abscess and sigmoidocutaneous fistula due to diverticulitis.

PMID- 22369796
TI  - Pneumothorax after laparoscopic extraperitoneal inguinal hernia repair: a
      potential complication that every general surgeon should know.

PMID- 22369797
TI  - Successful surgical treatment of emphysematous gastritis on a patient with poor
      cardiac function.

PMID- 22369798
TI  - Endoscopic clipping of bleeding ascending colon dieulafoy lesion.

PMID- 22369799
TI  - Periappendiceal mature cystic teratoma successfully treated with laparoendoscopic
      surgery.

PMID- 22369800
TI  - Compartment syndrome of the thigh as a complication of electromyography.

PMID- 22369801
TI  - Ileal diverticulitis.

PMID- 22369802
TI  - Post-emetic Lesions.

PMID- 22369803
TI  - Desmoid tumors.

PMID- 22369805
TI  - Rectal schwannoma (neurilemmoma).

PMID- 22369804
TI  - Successful treatment of a patient with colon cancer with congenital coagulation
      factor XI deficiency.

PMID- 22369806
TI  - Management of a patient with colocutaneous fistula by autologous platelet-rich
      fibrin glue.

PMID- 22369807
TI  - Excision and reconstruction of a giant basosquamous carcinoma of the anterior
      chest wall.

PMID- 22369808
TI  - Segmental portal vein thrombosis after repeat use of emergency contraceptive: a
      potential complication of high-dose progesterone.

PMID- 22369809
TI  - No sweat, a rare case of hidradenocarcinoma.

PMID- 22369810
TI  - Ipsilateral variations in the renal and vertebral arteries.

PMID- 22369811
TI  - Migration of a bullet leading to pulmonary embolus.

PMID- 22369812
TI  - Appendiceal cystadenoma: presentation, intraoperative and pathological findings.

PMID- 22369813
TI  - Squamous cell carcinoma of the nipple: an unusual location in a male patient.

PMID- 22369814
TI  - Operative procedure for pancreatoduodenectomy in a patient who had previously
      undergone total gastrectomy, distal pancreatectomy, and splenectomy.

PMID- 22369815
TI  - Surgical management of intestinal malrotation during laparoscopic Roux-en-Y
      gastric bypass.

PMID- 22369816
TI  - Cystosarcoma phyllodes and gastrointestinal stromal tumors: birds of the same
      feather?

PMID- 22369817
TI  - Management of primary epiploic appendagitis in the laparoscopic era.

PMID- 22369818
TI  - Symptomatic postoperative pneumoperitoneum after resection of giant ovarian
      masses.

PMID- 22369819
TI  - Isolated fallopian tube torsion: a rare entity in a premenarcheal female.

PMID- 22369820
TI  - Optimizing aesthetic results in skin grafting.
AB  - The aesthetic goal in skin grafting is to provide a cosmetically pleasing
      coverage of soft tissue defects while minimizing donor site morbidity. A skin
      graft should blend well with the color and texture of the surrounding skin,
      reduce wound size, and not interfere with the function  of the reconstructed
      part. This review examines the key components of choosing the appropriate donor
      skin for a variety of defects. The decision-making process is based on the
      anatomic location of the defect; donor site availability; and graft size,
      thickness, and pigmentation. The aesthetic  implications of using a sheet graft
      versus a meshed graft versus an expanded graft are discussed. Aside from
      addressing the aesthetic needs of the defect, attention is paid to the functional
      goals of the reconstructed part and reduced donor site morbidity. Partial graft
      failure  can have significant deleterious effects on the aesthetic outcome of
      skin grafts. The need for further grafting or healing by secondary intention may
      result in additional scarring and deformity. Recommendations for improvement in
      graft take and infection control are presented.

PMID- 22369821
TI  - John Blair Deaver, M.D., and his marvelous retractor.

PMID- 22369822
TI  - Cholangiocarcinoma: aggressive surgical intervention remains justified.
AB  - Cholangiocarcinoma (CCA) continues to be a difficult disease to both diagnose and
      treat. Optimal treatment includes resection to histologically negative margins.
      In recent years, advanced imaging, including magnetic resonance cholangiography
      and endoscopic ultrasound, has presumably  improved the accuracy of determining
      resectability. From 2004 to 2009, a total of 61 patients with cholangiocarcinoma
      were evaluated for resection. The majority were men (37) and ages ranged from 29
      to 87 years (mean, 67 years). Only 31 per cent were found to be obviously
      unresectable based  on imaging alone. The remaining 69 per cent underwent
      exploration, at which time resection was found unfeasible in an additional 25 per
      cent (overall 56% unresectable). Although all resection specimens had grossly
      negative margins, 37 per cent were ultimately found to be microscopically
      positive.  The overall 5-year actuarial survival for patients undergoing
      resection was 39.2 per cent with no survival difference between those with
      positive and negative margins. Despite advances in diagnostic imaging, more than
      half of patients with CCA presenting for surgical evaluation are ultimately 
      found to be unresectable. However, the final determination can still only be made
      at the time of exploration. Even in the presence of microscopic residual disease,
      surgical intervention results in improved survival. An aggressive stance toward
      surgical intervention in patients with CCA remains  justified.

PMID- 22369823
TI  - Organ donation and Hispanic american high school students: attitudes, beliefs,
      perceptions, and intent to donate.
AB  - The growing need for transplantable organs continues to outpace supply. This
      discrepancy is most pronounced in minority populations. Hispanic Americans,
      however, are significantly less likely to donate their organs for reasons that
      remain poorly understood. We sought to identify factors  that influence Hispanic
      American high school students' intent to donate organs. A prospective
      observational study was conducted in five Los Angeles high schools within four
      separate zip codes known for a high percentage of Hispanic Americans. High school
      students, ages 15 to 20 years,  were surveyed to assess demographic factors,
      cultural factors, awareness and knowledge, perception, and belief regarding organ
      donation and the intent to donate. A total of 5444 surveys were collected over a
      4-month period. After logistic regression analysis, independent risk factors for
      predicting  the intent to donate were: family support, 11th and 12th grade high
      school students, being female, religion, and the belief that Hispanics are more
      likely to need an organ transplant. This study represents the largest study to
      date examining factors associated with the intent to donate in  Hispanic American
      high school students. To address the organ shortage crisis in Hispanic Americans,
      these risk factors should be considered using specific, effective educational
      programs.

PMID- 22369824
TI  - Abdominoperineal resection without an abdominal incision for rectal cancer has
      the advantage of no abdominal wound complication and easier stoma care.
AB  - Abdominoperineal resection has been used for years for the management of low
      rectal cancer. However, the abdominal incision is associated with many
      complications and causes interference of the stoma care. If the abdominal
      incision can be avoided, it would be beneficial to the patient.  The aim of the
      study is to evaluate the possibility and safety of performing abdominoperineal
      resection and the oncology result without an abdominal incision. From September
      2001 to May 2010, 40 patients with rectal malignancies received excision of the
      rectum, anus, and perineum through a  perineal incision and a skin hole created
      for stomy. No harmonic scalpel or laser was used during surgery. No laparoscope
      or hand port was used in the procedure. There were 19 males and 21 females. Age
      ranged from 31 to 87 years old (average, 62.9 years). There were 39
      adenocarcinomas and  one malignant gastrointestinal stromal cell tumor. There was
      no operative mortality. Six patients had postoperative complications; three
      patients had intestinal obstructions; and one patient each had bleeding, urinary
      tract infection, and colostomy separation from the skin. The lymph nodes  in the
      specimens ranged from 9 to 33 cm (average, 16.8 cm). The survival is similar to
      the traditional abdominoperineal resection. This limited experience suggests that
      an abdominal incision is not necessary for radical resection of the rectum, anus,
      and perineum in patients with low-lying  rectal cancer. It also offers the
      patient easier care of stoma without interference of the abdominal incision.

PMID- 22369825
TI  - Right hemicolectomy is not routinely indicated in pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is primarily the result of a ruptured mucinous
      appendix neoplasm (MAN). Often MAN is lumped with but biologically distinct from
      intestinal appendiceal adenocarcinoma. Nodal and systemic dissemination are rare
      with the peritoneal cavity being the primary  site of recurrence. Routine
      performance of right hemicolectomy (RHC) for PMP/MAN has been extensively debated
      without consensus. Our objective was to ascertain whether RHC has a survival
      advantage over appendectomy. We hypothesize if RHC is mandatory, then increased
      tumor recurrence and mortality  should be observed in appendectomy only.
      Retrospective chart review was carried out in patients with tumors that met the
      Ronnett classification for PMP/MAN. Demographics, tumor grade, extent,
      recurrence, and progression were recorded. We report the rate of nodal
      involvement/recurrence in patients  treated with RHC versus appendectomy as well
      as the rate of systemic and peritoneal recurrence and survival. Multivariate
      logistic regression was done to identify factors that impact survival. Of 120
      patients, 48 had appendectomy and 72 had RHC. Seven per cent of patients
      undergoing  RHC had positive lymph nodes and no nodal failures (0%) in patients
      undergoing appendectomy. Appendectomy versus RHC recurrence rates (21 vs. 28%, P
      = 0.12) and death resulting from disease (8 vs. 22%, P = 0.27) were similar.
      Logistic regression revealed  that the type of surgery had no impact on
      recurrence and mortality, only optimal resection score and performance status.
      There was no difference in tumor recurrence or survival based on treatment by
      appendectomy or RHC. Performance status and complete cytoreduction are the only
      factors associated  with survival. Lymph node involvement is rare and selective
      RHC is safe in PMP/MAN.

PMID- 22369826
TI  - Is muscular atrophy a contraindication in laparoscopic abdominal wall defect
      repair? A prospective study.
AB  - Laparoscopic surgery for abdominal wall hernias improves short-term results as
      compared with open hernia surgery. However, no evidence exists to recommend this
      approach for pseudohernias, which are abdominal wall defects postsurgery caused
      by denervation and muscular atrophy. The purpose  of this study is to analyze
      whether the laparoscopic approach benefits patients with a pseudohernia. A
      prospective nonrandomized, single-center clinical study was conducted of 24
      patients operated on for pseudohernia. This study was designed with the basic
      principle of one unit, one surgeon,  one mesh, and two techniques (laparoscopic
      or open double prosthetic repair). The primary end point was assessment of the
      abdominal wall according to: 1) abdominal perimeter; 2) computed tomography scan;
      and 3) degree of satisfaction. The secondary end points were intraoperative
      parameters  and comorbidity. Laparoscopy offered no benefits in patients with
      pseudohernias. Open surgery offered no significant differences in intra- and
      postoperative morbidity, but if the initial weakness improved with a decrease in
      abdominal perimeter and visceral content, then there was more than  90 per cent
      satisfaction (P < 0.05). The laparoscopic approach does not improve the bulge
      caused by abdominal muscle atrophy. The option of a muscular and prosthetic
      reconstruction provides better clinical and cosmetic results.

PMID- 22369827
TI  - Diagnostic accuracy of intra-abdominal fluid collection characterization in the
      era of multidetector computed tomography.
AB  - The purpose of this study was to test the hypothesis that with improved
      technology, the presence of abscess in a postoperative fluid collection may be
      prospectively made. This is an Institutional Review Board-approved, Health
      Insurance Portability and Accountability Act-compliant retrospective  review of
      computed tomography (CT)-guided intra-abdominal fluid collection drainages. The
      diagnostic CT scans of 95 consecutive patients performed on 16- and 64
      multidetector CT (MDCT) were reviewed by four readers with varying abdominal
      imaging expertise. Readers were asked to determine fluid  content, to document
      whether infection was present, and to rate reader confidence for infection. A
      fifth radiologist reviewed the collections for imaging characteristics. The gold
      standard for presence of infection was microbiological Gram stain and culture.
      The logistic regression model showed  that both fluid collections containing gas
      or high attenuation fluid (average CT density 20 or greater Hounsfield units) are
      significant predictors of infection (P = 0.001). The average sensitivity over the
      four readers for determining presence of infection was 83.4 per cent and
      specificity  was 39.3 per cent. Even in the era of MDCT, the ability to predict
      whether or not a fluid collection is infected or not, based on imaging findings
      alone, is limited. Presence of gas is a strong indicator of infection, but no
      imaging finding is characteristic of a sterile fluid collection.

PMID- 22369828
TI  - Body mass index is a risk factor of pancreatic fistula after
      pancreaticoduodenectomy.
AB  - Pancreatic fistula (PF) after pancreaticoduodenectomy (PD) is still a severe
      complication and a challenging problem. The common risk factors are the soft
      pancreas and small pancreatic duct of the remnant pancreas. Those two risk
      factors were recognized during surgery. On the other hand,  a preoperatively
      determined risk factor of PF is unclarified. We conducted a retrospective
      analysis of 203 patients consecutively treated by PD from April 2000 to October
      2010. PF was defined according to the criteria of the International Study Group
      of Pancreatic Fistula. Clinical and pre-  and intraoperative data were compared
      between PF and non-PF patients. The recommended cutoff value of body mass index
      (BMI) as 20 kg/m(2) was defined by receiver operating characteristic curve
      analysis. PF occurred in 53 (26.1%) of 203 patients. In univariate analysis, BMI
      and soft  remnant pancreas were found to be risk factors of PF (P = 0.027, P =
      0.005). In multivariate analysis, BMI and soft pancreas were also risk factors of
      PF (P = 0.040, P = 0.005). Patients with PF had a significantly longer hospital
      stay than non-PF patients (P  = 0.005). High BMI and soft pancreas were
      significant risk factors for PF.

PMID- 22369829
TI  - The use of neural networks in identifying risk factors for lymph node metastasis
      and recommending management of t1b esophageal cancer.
AB  - The objective of this study was to establish a prediction model of lymph node
      status in T1b esophageal carcinoma and define the best squamous and
      adenocarcinoma predictors. The literature lacks a satisfactory level of evidence
      of T1b esophageal cancer management. We performed an analysis  pooling the
      effects of outcomes of 2098 patients enrolled into 37 retrospective studies using
      "neural networks" as data mining techniques. The percentages for lymph node,
      lymphatic (L+), and vascular (V+) invasion in Sm1 esophageal cancers were 24, 46,
      and 20 per cent, respectively.  The same parameters apply to Sm2 with 34, 63, and
      38 per cent as opposed to Sm3 with 51, 69, and 47 per cent. The respective number
      of patients with well, moderate, and poor histologic differentiation totaled 267,
      752, and 582. The rank order of the predictors of lymph node positivity was, 
      respectively: Grade III, (L+), (V+), Sm3 invasion, Sm2 invasion, and Sm1
      invasion. Histologic-type squamous and adenocarcinoma (ADC/SCC) was not included
      in the model. The best predictors for SCC lymph node positivity were sm3 invasion
      and (V+). As concerns ADC, the most important predictor  was (L+). Submucosal
      esophageal cancer should be managed with surgical resection. However, this is
      subject to the histologic type and presence of specific predictors that could
      well alter the perspective of multimodality management.

PMID- 22369830
TI  - Single versus multi-specialty operative teams: association with perioperative
      mortality after endovascular abdominal aortic aneurysm repair.
AB  - Endovascular abdominal aortic aneurysm repair (EVAR) requires both endovascular
      and open surgical skills. Although usually performed by a single operating
      specialist, EVAR may alternatively involve multiple teams from different
      specialties performing separate procedural components.  We examined the relative
      frequencies of single versus multi-specialty EVAR in the 2005 to 2008 American
      College of Surgeons National Surgical Quality Improvement Participant Use
      Datafile and explored the influence of multi-specialty EVAR on 30-day mortality.
      EVARs were identified and  classified as single or multiple-specialty procedures
      based on Current Procedural Terminology codes. Baseline and procedural
      characteristics were compared using chi(2) or Fisher's exact test for categorical
      variables and t test for continuous variables. The association between  multi
      specialty EVAR and 30-day mortality was examined using a multivariate logistic
      regression model. Of 7269 EVAR patients identified, 7086 were single and 183 were
      multi-specialty. Multi-specialty patients had higher frequency of brachial or
      iliac artery exposure and longer operative times,  but were otherwise similar in
      baseline and procedural characteristics. In the multivariate model, multi
      specialty EVAR was associated with increased risk of 30-day mortality (odds ratio
      2.35; 95% confidence interval 1.08-5.11; P value 0.031). Multi-specialty
      participation in  EVAR procedures is associated with significantly higher 30-day
      mortality. Further research is warranted to determine whether multi-specialty
      participation reflects provider experience, institutional protocols, procedural
      complexity, non-surgical or other factors.

PMID- 22369831
TI  - Outpatient laparoscopic appendectomy for acute appendicitis.
AB  - Laparoscopic appendectomy is the widely accepted treatment for acute
      appendicitis. This approach offers the potential of less pain, shorter hospital
      stay, and quicker return to activities. Traditionally, patients are hospitalized
      for 24 hours after laparoscopic appendectomy. This practice  can be questioned
      due to the good results of other outpatient laparoscopic surgery. A retrospective
      review of 119 patients undergoing laparoscopic appendectomy for uncomplicated
      acute appendicitis was undertaken from January through September 2009; outpatient
      and inpatient laparoscopic appendectomies  were compared. Patients were selected
      for outpatient management based upon physician discretion and their clinical
      course in operation and recovery rooms. Forty-two patients were dismissed on the
      day of surgery and 77 were admitted for 1 to 5 days postoperatively. No
      significant differences  in age, gender, and preoperative comorbidities between
      outpatient and inpatient groups were found. Postoperative complications occurred
      in 2.4 per cent of outpatients and 11.7 per cent of inpatients (P = 0.16).
      Complications included superficial wound infections, urinary retention,  urinary
      tract infection, intra-abdominal bleeding, pneumonia, and infected hematoma.
      Based upon this study, outpatient laparoscopic appendectomy can be performed
      safely in selected patients. This study provides the background for the present
      prospective protocol for routine outpatient laparoscopic  appendectomy at our
      institution.

PMID- 22369832
TI  - Surgical outcomes of solid pseudopapillary neoplasm of the pancreas: a single
      institution's experience for the last ten years.
AB  - Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that
      accounts for about 1 to 2 per cent of all pancreatic tumors. The aim of this
      study was to delineate the clinicopathological characteristics and surgical
      outcomes of solid pseudopapillary neoplasm of the pancreas.  We retrospectively
      reviewed the clinicopathological characteristics and surgical outcomes of 18
      patients who underwent surgery for SPN of the pancreas between January 1, 2001
      and November 1, 2010. The patient group was comprised of 14 females and four
      males and the median patient age at diagnosis  was 32.4 years (range 10~68
      years). Eleven of the 18 patients were symptomatic at the time of diagnosis. The
      type of surgery was selected according to the location and presentation of the
      tumor. The resection margins were negative in all patients. One patient had
      distant metastasis and  recurrent mass node repetitively. She underwent seven
      operations for recurrence of SPN during the follow-up period of 218 months.
      Complete surgical excision is the treatment of choice for SPN of the pancreas and
      can give a good prognosis. Although sometimes patients have repetitive metastases
      or recurrences, patients undergoing complete surgical excision of the tumor will
      have a good outcome.

PMID- 22369833
TI  - Acute acalculous cholecystitis after gastrointestinal surgery.
AB  - Acute acalculous cholecystitis has been identified as a rare but potentially
      devastating entity after trauma, and burns, as well as in critically ill
      patients, and in the postoperative period. Gastrointestinal surgery is most
      frequently implicated in postoperative acute acalculous cholecystitis, 
      especially after gastric and colorectal procedures. Review of the English
      literature identified 28 articles reporting 76 cases of acute acalculous
      cholecystitis after gastrointestinal operations, which included a case from
      Tulane University Medical Center of a 64-year-old man who developed 
      postoperative acute acalculous cholecystitis after elective left hemicolectomy. A
      total of 52.4 per cent of the patients developed gangrenous acute acalculous
      cholecystitis, with a mortality rate of 21.1 per cent, much higher than that
      reported in postoperative calculous cholecystitis. This  emphasizes the need for
      a high level of suspicion and early detection in the postoperative period to
      avoid devastating consequences.

PMID- 22369834
TI  - Hospital volume, margin status, and long-term survival after
      pancreaticoduodenectomy for pancreatic adenocarcinoma.
AB  - An association between hospital surgical volume and short- and long-term outcomes
      after pancreatic surgery has been demonstrated. Identification of specific
      factors contributing to this relationship is difficult. In this study, the
      authors evaluated if margin status can be identified  as a measure of surgical
      quality, affecting overall survival, as a function of hospital
      pancreaticoduodenectomy volume. A systematic review of the literature was
      performed. Two models for analysis were created, dividing the 18 studies
      identified into quartiles and two quantiles based on the  average annual hospital
      pancreatectomy volume. Regression modeling and analysis of variance were used to
      find an association between hospital volume, margin status, and survival.
      Increasing hospital volume was associated with a significantly increased negative
      margin status rate: 55 per cent  for low-volume, 72 per cent for medium-volume,
      74.3 per cent for high-volume, and 75.7 per cent for very high-volume centers (P
      = 0.008). The negative margin status rates were 64 per cent and 75.1 per cent for
      volume centers with less and more than 12 pancreaticoduodenectomies/year, 
      respectively (P = 0.04). Low-volume centers negatively affected both margin
      positive resection and 5-year survival rates, compared with high-volume centers.
      Margin status rate after pancreaticoduodenectomy could, therefore, be considered
      a measure of quality for selection of hospitals  dedicated to pancreatic surgery.

PMID- 22369835
TI  - Preoperative functional health status impacts outcomes after ventral hernia
      repair.
AB  - Associated with the aging population is an increase in comorbidities and a
      decrease in the ability to perform basic daily activities. This is tracked within
      the American College of Surgeons National Surgical Quality Improvement Program
      (ACS-NSQIP) as a patient's preoperative functional  health status. Our goal was
      to evaluate the impact of preoperative functional status upon outcomes after
      ventral hernia repair. We reviewed all cases of patients that underwent ventral
      hernia repair from 2005 to 2010 in the ACS-NSQIP database. Patients were
      identified based on selected Current  Procedural Terminology codes and grouped
      based on functional status as listed in the ACS-NSQIP database-independent,
      partially dependent, and totally dependent. Preoperative and operative variables
      were recorded for all patients. Clinical risk factors and short-term outcomes
      between  groups were compared. Multivariable logistic regression was used to
      adjust for age, wound class, American Society of Anesthesiologists class, and
      case relative value units. A total of 76,397 patients were identified: 74,785
      were independent (97.9%), 1,317 partially dependent (1.7%), and 295  totally
      dependent (0.4%). Totally dependent patients had an increased risk for all short
      term outcomes after ventral hernia repair: wound occurrence, pneumonia, pulmonary
      embolism, urinary tract infection, myocardial infarction, deep venous thrombosis,
      sepsis, return to the operating room,  and death (P < 0.001 for all).

PMID- 22369836
TI  - Late initiation of continuous veno-venous hemofiltration therapy is associated
      with a lower survival rate in surgical critically ill patients with postoperative
      acute kidney injury.
AB  - There is controversy about the appropriate timing for renal replacement therapy
      in patients with acute kidney injury (AKI). We are interested in the appropriate
      timing for initiation of continuous renal replacement therapy in critically ill
      surgical patients with postoperative acute  kidney injury. Seventy-three
      critically ill surgical patients with postoperative AKI who received continuous
      renal replacement therapy (CRRT) were enrolled. Indications for CRRT were: 1) AKI
      with hyperkalemia, 2) metabolic acidosis, 3) pulmonary edema refractory to
      diuretics, and 4) oliguria  with progressive azotemia, especially in unstable
      hemodynamics. Using RIFLE (Risk, Injury, Failure, Loss, End stage)
      classification, patients who received CRRT in the "Risk" stage were defined as
      early group, whereas those in the "Injury/ Failure" stage were labeled  as late
      group. We used continuous veno-venous hemofiltration as CRRT in this series.
      There were 20 patients in the early group and 53 patients in the late group. The
      mean ages were 61.5 +/- 21.8 years versus 60.8 +/- 17.5 years. The mortality rate
      was 50 per cent versus  84.9 per cent. There were no significant differences in
      demographic characteristics or type of surgery or physiological scores. Our data
      show that late initiation of CRRT is associated with a lower survival rate in
      critically ill surgical patients with postoperative AKI; however, further studies
      are required.

PMID- 22369837
TI  - Outcomes for incisional hernia repair in patients undergoing concomitant surgical
      procedures.
AB  - The safety and efficacy of performing concomitant surgical procedures with an
      incisional hernia repair (IHR) is not well understood. There are conflicting
      reports on the outcomes for permanent mesh implantation in the setting of clean
      contaminated procedures. The purpose of this study  was to review the effect of
      concomitant surgical procedures on IHR outcomes. This is a retrospective
      multisite cohort of patients undergoing elective IHR at 16 Veterans Affairs
      hospitals from 1998 to 2002. Concomitant procedure status, hernia
      characteristics, and operative details were determined  using physician
      abstracted operative notes. Hernia outcomes of recurrence and mesh explantation
      were determined from the medical chart. chi(2) tests, Kaplan-Meier curves, and
      Cox regression were used to evaluate the effects of concomitant status on hernia
      outcomes. Of the 1495 elective  IHRs, 75 (4.8%) were same site and 56 (3.8%)
      different site concomitant procedures. At median follow-up of 69.3 months (range
      19.1-98.3), 33.6 per cent of patients had a recurrence, mesh explantation, or
      both. Permanent mesh placement was less likely among concomitant procedures as 
      compared with nonconcomitant procedures (P < 0.0001). Adjusted Cox proportional
      hazards models of hernia outcomes resulted in an increased hazard for recurrence
      among same site clean procedures (Hazard Ratio (HR) = 1.8, P = 0.03) and an
      increased hazard for mesh explantation  among same site clean-contaminated
      procedures (HR = 8.4, P = 0.002). Concomitant same site procedures are
      significantly associated with adverse hernia outcomes as compared with isolated
      IHR or IHR with other site concomitant procedures. The high failure rate of
      hernia repairs among  same site concomitant procedures should be taken into
      account during the surgical decision-making process.

PMID- 22369838
TI  - As-needed antihypertensive therapy in surgical patients, why and how: challenging
      a paradigm.
AB  - Hypertension is common in hospitalized patients and there are many causes. Some
      patients have no prior history of hypertension, few symptoms, and no apparent
      morbidity related to acute rises in blood pressure. Though there is no
      established guideline for therapy in these cases, patients  often receive therapy
      directed at the abnormal vital sign. It is hypothesized that this practice is
      common and the associated costs are significant. Using the inpatient pharmacy
      database at the University of Kentucky Chandler Medical Center, a verified Level
      I trauma center and quaternary  referral center, patients on the emergency
      general surgery or orthopedic surgery services receiving intravenous hydralazine,
      metoprolol, or labetalol were identified. Subjects were analyzed for indications,
      parameters, associated history of hypertension, and direct costs. Over the 4
      month  study period, 114 subjects received 522 drug doses. More than half (55%)
      of subjects had a prior history of hypertension but only 75 per cent were started
      on their home medication. Of those without hypertension before admission, 18 per
      cent required therapy at discharge. Labetalol was the  most frequently used agent
      and total pharmacy costs for this cohort of patients was over $1200. Pro re nata
      (PRN), short-acting antihypertensive therapy has little evidence base in
      asymptomatic patients, but its prevalence is high on surgical services. The cost
      is significant, especially  when extrapolated to the larger hospital population
      at this single institution. Further research is warranted to determine the
      prevalence of this practice in other centers or national regions, as well as its
      cost and benefit.

PMID- 22369839
TI  - Obesity does not impact outcomes for appendicitis.
AB  - Obesity has long been considered a risk factor for surgery. The purpose of this
      study was to evaluate the impact of obesity on outcomes after appendectomy. A
      retrospective study was performed using discharge abstract data obtained from
      patients with documented body mass index (BMI)  undergoing appendectomy for
      appendicitis (n = 2919). Complications and length of stay for different BMI
      categories were compared. Obese patients (BMI > 30 kg/m(2)) had similar rates of
      perforation (20%) and were as likely to undergo a laparoscopic approach (85%) as
      nonobese patients.  On multivariable and univariate analysis, no significant
      differences were observed when comparing obese and nonobese patients for the
      outcomes of length of stay, infectious complications, and need for readmission.
      On multivariate analysis, laparoscopy predicted lower complication rates and 
      decreased length of stay. In this study, obesity did not significantly impact
      rates of perforation, operative approach, length of stay, infectious
      complications, or readmission.

PMID- 22369840
TI  - Malignant transformation of a pancreatic serous cystadenoma.

PMID- 22369841
TI  - Adjustable gastric band prolapse leading to near-fatal hemorrhage.

PMID- 22369842
TI  - A true congenital internal hernia identified after a motor vehicle collision.

PMID- 22369843
TI  - Combined variations of the visceral branches of the abdominal aorta.

PMID- 22369844
TI  - A novel procedure to accomplish end-to-side colonic anastomoses.

PMID- 22369845
TI  - Comparison of adenoma detection rates between gastroenterologists and colorectal
      surgeons.

PMID- 22369846
TI  - Characterization of dissolved organic matter using high-performance liquid
      chromatography (HPLC)-size exclusion chromatography (SEC) with a multiple
      wavelength absorbance detector.
AB  - High-performance liquid chromatography-size exclusion chromatography (HPLC-SEC)
      coupled with a multiple wavelength absorbance detector (200-445 nm) was used in
      this study to investigate the apparent molecular weight (AMW) distributions of
      dissolved organic matter (DOM). Standard DOM, namely humic acid, fulvic acid and
      hydrophilic acid, from the Suwannee River were tested to ascertain the
      performance and sensitivity of the method. In addition to four compounds groups:
      humic substances (Peak 1, AMW 16 kD), fulvic acids (Peak 2, AMW 11 kD), low AMW
      acids (Peak 3, AMW 5 kD), and low AMW neutral and amphiphilic molecules, proteins
      and their amino acid building blocks (Peak 4, AMW 3 kD), an new group that
      appears to include low AMW, 6-10 kD, humic substances was found based on
      investigating the spectra at various elution times. The spectroscopic parameter
      S(>365) (slope at wavelengths >365 nm) was determined to be a good predictor of
      the AMW of the DOM. The detector wavelength played an important role in
      evaluating the AMW distribution. For some fractions, such as the humic and low
      AMW non-aromatic substances, the error in measurement was +/- 30% as determined
      by two-dimensional chromatograms detected at an artificially selected wavelength.
      HPLC-SEC with multiple wavelength absorbance detection was found to be a useful
      technique for DOM characterization. It characterized the AMW distributions of DOM
      more accurately and provided additional, potentially important information
      concerning the properties of DOM with varying AMWs.

PMID- 22369847
TI  - Improved solubilization of activated sludge by ozonation in pressure cycles.
AB  - The generation of a large volume of activated sludge (AS) from wastewater
      treatment has increasingly become a great burden on the environment. Anaerobic
      digestion is routinely practiced for excess waste sludge; however, the process
      retention time is long because of kinetic limitation in the hydrolysis step. We
      tested the feasibility of applying ozone in pressure cycles to enhance the
      disintegration and solubilization of AS with the goal to prepare them for
      digestion using reduced ozone dose and contact time. The AS was subjected to
      repetitive pressure cycles in a closed vessel in which an ozone gas mixture was
      compressed into the slurry to reach 1040 kPa in the headspace to be followed by
      rapid venting. For a returned AS with total COD (tCOD) of 8200 mg L(-1), a dose
      of 0.01 gO(3)g(-1) total suspended solids (TSS) delivered via 20 pressure cycles
      within 16 min resulted in a 37-fold increase of the sCOD/tCOD ratio (due to
      increased soluble COD, i.e. sCOD) and a 25% reduction of TSS, in comparison to a
      dose of 0.08 gO(3)g(-1) TSS via bubbling contact over 15 min that resulted in a
      15-fold increase of the sCOD/tCOD ratio and a 12% reduction of TSS. Sludge
      solubilization was evidenced by increased dissolved contents of total phosphorous
      (from 10 to 64 mg L(-1)), total nitrogen (from 14 to 120 mg L(-1)), and protein
      (from <15 to 39 mg L(-1)) in the sludge suspension after treatment, indicating
      significant solubilization of AS.

PMID- 22369848
TI  - Effect of vitamin A deficiency on the immune response in obesity.
AB  - Obesity has been associated with low-grade systemic inflammation and with
      micronutrient deficiencies. Obese individuals have been found to have lower
      vitamin A levels and lower vitamin A intake compared with normal-weight
      individuals. Vitamin A plays a major role in the immune function, including
      innate immunity, cell-mediated immunity and humoral antibody immunity. It has
      also been recognised recently that vitamin A has important regulatory functions.
      Vitamin A status has an important effect on the chronic inflammatory response.
      Vitamin A deficiency increases a T-helper type 1 (Th1) response, elevates levels
      of pro-inflammatory cytokines, increases the expression of leptin, resistin and
      uncoupling proteins (UCP) and promotes adipogenesis. The effect of vitamin A
      deficiency on obesity might be increasing the risk of fat deposition and also the
      risk of chronic inflammation associated with obesity. Supplementation with
      vitamin A in vitro and in animal models has been found to reduce concentrations
      of adipocytokines, such as leptin and resistin. In conclusion, vitamin A
      deficiency increases a Th1 response in the presence of obesity and thus,
      increases the inflammatory process involved in chronic inflammation and fat
      deposition. The metabolism of leptin and other adipocytokines may play a critical
      role in the effect of vitamin A deficiency in the inflammatory response observed
      in obesity.

PMID- 22369851
TI  - Ethical, legal and social issues: out in the open.

PMID- 22369852
TI  - Celastrol suppresses growth and induces apoptosis of human hepatocellular
      carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in
      vivo.
AB  - Cumulative evidences(s) have established that the constitutive activation of
      STAT3 plays a pivotal role in the proliferation, survival, metastasis, and
      angiogenesis and thus can contribute directly to the pathogenesis of
      hepatocellular carcinoma (HCC). Thus, novel agents that can inhibit STAT3
      activation have potential for both prevention and treatment of HCCs. The effect
      of celastrol on STAT3 activation, associated protein kinases, STAT3-regulated
      gene products, cellular proliferation, and apoptosis was investigated. The in
      vivo effect of celastrol on the growth of human HCC xenograft tumors in athymic
      nu/nu mice was also examined. We observed that celastrol inhibited both
      constitutive and inducible STAT3 activation, and the suppression was mediated
      through the inhibition of activation of upstream kinases c-Src, as well as Janus
      activated kinase-1 and -2. Vanadate treatment reversed the celastrol-induced
      modulation of STAT3, suggesting the involvement of a tyrosine phosphatase. The
      inhibition of STAT3 activation by celastrol led to the suppression of various
      gene products involved in proliferation, survival, and angiogenesis. Celastrol
      also inhibited the proliferation and induced apoptosis in HCC cells. Finally,
      when administered intraperitoneally, celastrol inhibited STAT3 activation in
      tumor tissues and the growth of human HCC xenograft tumors in athymic nu/nu mice
      without any side effects. Overall, our results suggest for the first time that
      celastrol exerts its antiproliferative and proapoptotic effects through
      suppression of STAT3 signaling in HCC both in vitro and in vivo.

PMID- 22369853
TI  - Prolame ameliorates anxiety and spatial learning and memory impairment induced by
      ovariectomy in rats.
AB  - N-(3-hydroxy-1, 3, 5 (10) estratrien-17beta-yl)-3-hydroxypropylamine (17beta
      aminoestrogen, prolame) is a steroidal compound with weak estrogen-related
      trophic-proliferative effects in uterus. Contrasting with 17beta-estradiol (E2)
      pro-coagulant effects, this compound has high anticoagulant and antiplatelet
      effects. It has been extensively demonstrated that E2 plays important roles in
      brain function. However, prolame's influence on central nervous system has not
      been documented. In this study, we evaluated the effects of prolame replacement
      in young ovariectomized rats on spatial learning and memory and anxiety,
      correlating pyramidal cell dendritic spine density changes and neuronal nitric
      oxide synthase (nNOS) expression in the hippocampus. Ovariectomized young rats
      were treated with prolame for 4 weeks. Three other groups were used as
      physiological, pathological, and pharmacological references as follow: gonadally
      intact cycling females, ovariectomized, and ovariectomized with 17beta-estradiol
      treatment respectively, for the same time period. Experiment 1 investigated the
      behavioral effects of prolame on anxiety and spatial learning using elevated plus
      maze (EPM) and Morris water maze (MWM) paradigms respectively. Experiment 2
      studied the dendritic spine density and neuronal nitric oxide synthase expression
      in the hippocampus of the 4 experimental groups. Similar to estradiol, prolame
      reversed the anxiogenic effects of ovariectomy, evaluated by EPM, and enhanced
      MWM performance to the level of gonadally intact subjects. Hippocampi from
      prolame-treated rats exhibited enhanced nNOS immunoreactivity and its relocation
      in dendritic compartments, as well as recovery of dendritic spine density loss in
      pyramidal neurons. Hence, prolame may provide an alternative option for
      ameliorating neurological symptoms caused by surgical menopause.

PMID- 22369854
TI  - Biomechanical events of swallowing are determined more by bolus consistency than
      by age or gender.
AB  - The biomechanics of swallowing saliva and substances of different consistencies
      were investigated in healthy children and adults. To this end, the duration and
      mean amplitude value (MAV) of surface electromyography (sEMG) of the submental
      muscle group (SMG) activity, the maximum anterior tongue pressure (ATP), and the
      rise and release slopes of ATP were measured while participants (39 female and 39
      male participants, age 5-65 years) swallowed saliva, 5 mL water (reference), 5 mL
      thick liquid, and 5 mL solid food. Mean outcome parameters varied with the
      consistency of the liquid or food swallowed, with the exception of the rise slope
      of ATP. Moreover, outcome variables were not substantially affected by age with
      children of 5 years and older showing similar biomechanical events to those of
      adults. It is important to gain insight into the biomechanics of swallowing
      saliva and substances of different consistencies in order to understand the
      underlying mechanisms of dysphagia children and adults.

PMID- 22369855
TI  - Structure guided approaches toward exploiting and manipulating nonribosomal
      peptide and polyketide biosynthetic pathways.
AB  - Nonribosomal peptide and polyketide natural products are structurally diverse
      small molecules synthesized on complex enzyme assemblies. The ability to
      rationally engineer secondary metabolic pathways is a promising approach to novel
      therapeutics. Atomic resolution structures of biosynthetic enzymes provide
      information on active site architecture and macromolecular assembly that can aid
      in the engineering of new compounds. This review surveys recent applications
      toward biosynthetic engineering of natural products guided by structural biology.

PMID- 22369856
TI  - Hepatocellular carcinoma targeting effect of PEGylated liposomes modified with
      lactoferrin.
AB  - A hepatocellular carcinoma targeting lactoferrin (Lf) modified PEGylated liposome
      system was developed for improving drug efficacies to hepatic cancer cells. In
      this present work, PEGylated liposomes (PLS) were successfully prepared by the
      thin film hydration method combined with peglipid post insertion. Lf was
      covalently conjugated to the distal end of DSPE-PEG2000-COOH lipid by amide bound
      and loaded onto PEGylated liposomes surface as the targeting ligand. To confirm
      the targeting efficacies to hepatic cancer, coumarin-6 and DiR were encapsulated
      as fluorescent probes. The confocal microscopy and flow cytometry demonstrated
      that Lf conjugated PEGylated liposomes (Lf-PLS) were efficiently associated by
      HepG2 cells, while limited interaction was found for liposomes modified with a
      negative control protein. A similar pharmacokinetic behavior was observed in
      pharmacokinetics study of the liposomal formulations. Meanwhile, the in vivo
      imaging of liposomes in HepG2 tumor bearing mice indicated that Lf-PLS achieved
      more accumulation in tumor compared with PLS without Lf conjugated. The
      significant in vitro and in vivo results suggested that Lf-PLS might be a
      promising drug delivery system for hepatocellular carcinoma therapy with low
      toxicity.

PMID- 22369857
TI  - Assessment of novel oral lipid-based formulations of amphotericin B using an in
      vitro lipolysis model.
AB  - The purpose of this study was to investigate the intraluminal processing of novel
      oral lipid-based formulations of amphotericin B using an in vitro lipolysis
      model. Amphotericin B (AmB) was formulated in three lipid-based formulations
      consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various
      lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to
      assess AmB distribution among the lipolysis phases. The duration of lipolysis was
      comparable among the three formulations except for 2 g load of iCo-009 which had
      a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components
      of iCo-009 experienced lower extent of lipolysis as compared to other
      formulations. Amphotericin B concentration in the aqueous phases was the highest
      with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels
      in the undigested lipid layers were comparable between iCo-009 and iCo-010 and
      were higher than with iCo-011. Given the observation that iCo-010 had the highest
      aqueous micellar solubilization and the lowest sediment recovery of AmB among the
      tested formulations, these results could potentially be used to interpret and
      predict the in vivo performance of AmB- SEDDS formulations in future studies.

PMID- 22369858
TI  - Mixed micelles of PEG(2000)-DSPE and vitamin-E TPGS for concurrent delivery of
      paclitaxel and parthenolide: enhanced chemosenstization and antitumor efficacy
      against non-small cell lung cancer (NSCLC) cell lines.
AB  - Concurrent combination of chemotherapeutic drugs is a promising alternative to
      single-agent therapies in cancer. In the present study, paclitaxel and
      parthenolide were loaded into mixed micelles and tested against taxol sensitive
      (A549) and resistant (A549-T24) NSCLC cell lines. Combination chemotherapy was
      further evaluated by isobologram analyses and combination index calculations.
      Drugs were loaded into micelles by the film casting method using PEG(2000)-DSPE
      and vitamin E-TPGS. Micelle characterization studies included the determination
      of particle size, encapsulation efficiency, in vitro release kinetics, as well as
      1H NMR analysis. The in vitro release of both drugs was slower from the mixed
      micelles, which maintained an encapsulation efficiency >95% and chemical
      stability over a storage period of 45 days. The IC50 of paclitaxel and
      parthenolide determined by MTT assay were 108.6nM and 21MUM, respectively, while
      the combination had an IC50 of 64.15nM in A549 cells. In the taxol resistant cell
      lines, the IC50 values of paclitaxel and parthenolide were 233nM and 32MUM,
      respectively, while the combination had an IC(50) of 128nM. The efficacy of
      paclitaxel and parthenolide against both cell lines significantly increased when
      the drugs were coencapsulted in mixed micelles. Mixed micelles caused 79% cell
      death, which was significantly higher than the 46% cell death caused by the drugs
      in solution against taxol sensitive cell lines. In taxol resistant cell lines,
      the cell death caused by mixed micelles was 70% as compared to 45% cell death
      caused by un-encapsulated drugs. Co-encapsulation of parthenolide with paclitaxel
      in mixed micelles increased the anticancer activity of paclitaxel against
      resistant and sensitive lung cancer cell lines.

PMID- 22369859
TI  - Similarities and differences between the effects of EPA and DHA on markers of
      atherosclerosis in human subjects.
AB  - We have reviewed effects of long chain (LC) n-3 PUFA on markers of
      atherosclerosis in human subjects with a focus on individual effects of EPA and
      DHA. Initial results from epidemiological studies suggested that LC n-3 PUFA from
      fish oils (FO) reduced incidence of CVD; those results have been confirmed in
      interventional studies. Dietary intervention with n-3 PUFA decreased fasting and
      postprandial TAG, number of remnant-like chylomicron particles, large VLDL, and
      total and small dense LDL particles. It increased mean size of LDL particles by
      increasing number of large and decreasing those of small dense particles. With
      some exceptions, n-3 PUFA decreased blood pressure (BP) and heart rate (HR), flow
      mediated dilation (FMD) and plasma concentrations of inflammatory markers. n-3
      PUFA also decreased circulating adhesion molecules and intima-media thickness
      (IMT) in some but not other studies. For IMT, results varied with the sex and
      artery being examined. EPA effects on FMD are endothelial cell dependent, while
      those of DHA seem to be endothelial cell independent. Individually, both EPA and
      DHA decreased TAG and inflammatory markers, but only DHA decreased HR, BP and
      number of small dense LDL particles. Results varied because of dose and duration
      of n-3 PUFA, EPA:DHA, health status of subjects and other reasons. Future studies
      are needed to determine optimal doses of EPA and DHA individually, their
      synergistic, additive or antagonistic effects, and to understand underlying
      mechanisms. In conclusion, n-3 PUFA decreased several risk factors for
      atherosclerosis without any serious adverse effects.

PMID- 22369860
TI  - Superiority of 18F-FDG PET compared to 111In-labelled leucocyte scintigraphy in
      the evaluation of fever of unknown origin.
AB  - AIM: To compare the accuracy of positron emission tomography (PET) using (18)F
      FDG (Fluorodeoxyglucose) PET with (111)In-labelled leucocytes scintigraphy (LS)
      in patients with fever of unknown origin (FUO). METHODS: Twenty-three consecutive
      patients with FUO were prospectively studied using whole-body LS and PET.
      Performance of the two modalities for identifying a cause of FUO was evaluated.
      Final diagnosis was based on biopsy, microbiological tests, clinical and imaging
      follow-up. RESULTS: Abnormal tracer uptake was seen in 3/23(13%) and 14/23(61%)
      patients on LS and PET respectively, suggesting a higher sensitivity (p < 0.01)
      for the latter. All LS positive cases were identified on PET and confirmed as
      infection. The causes of FUO in the other PET positive patients were: infection
      (n = 3), vasculitis (n = 3), non-infectious inflammatory conditions (n = 2) and
      cancer (n = 1). No specific diagnosis was reached in 2 patients. Of 13 patients
      without a definite diagnosis following PET and LS, 10 made a spontaneous recovery
      during the follow-up period and no definite cause for FUO was found on
      investigation. Still's disease, Polymyalgia rheumatica and Chronic fatigue
      syndrome/Myalgic encephalomyelitis were diagnosed in the remaining three patients
      during follow-up. The results thus showed an overall sensitivity of 86% for PET
      and 20% for LS (p < 0.01). The overall specificity for FDG PET was 78% as against
      100% for LS. PET had a PPV of 86% and a NPV of 78% whereas LS had a PPV of 100%
      and a NPV of 40%. CONCLUSION: PET has a higher sensitivity than LS in identifying
      the aetiology of FUO. PET/PET-CT, where available, should be used as the non
      invasive investigation of choice in the assessment of patients with FUO.

PMID- 22369861
TI  - Emerging trends in candidemia: a higher incidence but a similar outcome.
AB  - The clinical presentation and outcome of candidemia has changed in recent years.
      We compared two 5-year periods (2000-2004 and 2005-2009) in a single institution.
      We recorded 419 candidemia episodes during the study period (124 in the first
      period and 295 in the second period). We observed a significant increase in the
      number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009
      (chi(2) LT <0.001). Candida albicans was the most frequently isolated species
      (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%).
      In the second period, episodes were associated with higher comorbidity and were
      more commonly nosocomial, with a more frequent catheter-related source and an
      increased rate of C. glabrata infection. No significant differences were observed
      in susceptibility by species during the study period. According to multivariate
      analysis, the independent factors associated with higher mortality were shock,
      age >50 years, elevated comorbidity score (Charlson index >6), and source of
      candidemia other than catheter. In contrast to the increase in comorbid
      conditions observed in recent years, mortality remained similar during both
      periods (~37% during the first month). This finding could be attributed to a
      significant increase in catheter-related candidemia and better outcome, as well
      as to a potential improvement in the management of antifungal therapy in recent
      years.

PMID- 22369862
TI  - Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR
      Studies of raltegravir derivatives as HIV-1 inhibitors.
AB  - A series of raltegravir derivatives 20-42 were prepared and systematically
      evaluated for their anti-HIV activity. The bioassay results showed that most of
      the compounds possess good to excellent anti-HIV activity. Especially, compounds
      25 and 35 with subpicomole IC(50) values seemed to be the most potent anti-HIV
      agents among all of the reported synthesized compounds. These compounds may
      therefore be considered as new potent anti-HIV agents. The 5-hydroxyl
      modification of raltegravir derivatives significantly increased the anti-HIV
      activity, which indicates that the hydroxyl may not be indispensable for
      raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is
      favorable for antiviral activity. In addition, a high-throughput cell-based assay
      method with pseudotyped virus stocks was developed and used to identify HIV
      inhibitors.

PMID- 22369863
TI  - Environmental assessment of energy production based on long term commercial
      willow plantations in Sweden.
AB  - The present paper analyzed the environmental assessment of short rotation willow
      plantations in Sweden based on the standard framework of Life Cycle Assessment
      (LCA) from the International Standards Organisation. The analysis is focused on
      two alternative management regimes for willow plantations dedicated to biomass
      production for energy purposes. The data used included the averages of a large
      sample of commercial plantations. One of the scenarios is carried out under
      nitrogen based fertilized conditions and the other under non-fertilized
      management with total biomass yields (dry weight) of 140t/ha and 86t/ha over a 21
      and 22-year life time respectively. The environmental profile was analyzed in
      terms of the potentials for abiotic depletion, acidification, eutrophication,
      global warming, ozone layer depletion, photochemical oxidant formation, human
      toxicity, fresh water aquatic ecotoxicity, marine aquatic ecotoxicity and
      terrestrial ecotoxicity. In addition, an energy analysis was performed using the
      cumulative energy demand method (CED). The application of nitrogen based
      fertilizers allows an increase in the biomass yield per ha of up to 40% although
      the contributions to almost all impact categories, particularly the
      eutrophication potential and toxicity potential impact categories are also
      considerably higher. Conversely, due to the higher biomass yields achieved with
      fertilization of these willow plantations, that regime presents a better overall
      environmental profile in terms of energy yield and global warming potential.

PMID- 22369864
TI  - Pilot estuarine mesocosm study on the environmental fate of Silver nanomaterials
      leached from consumer products.
AB  - Although nanosilver consumer products (CPs) enjoy widespread availability, the
      environmental fate, leaching, and bioaccumulation behaviors of silver
      nanoparticles (AgNPs) from these products are not well understood. In this work,
      three nanosilver CPs, two AgNP standards, and an ionic silver (Ag(+)) standard
      were studied in estuarine mesocosms. The CPs exhibited long-term release of
      significant amounts of silver over a 60d residence time in the mesocosms, and
      ultimately released 82 - 99% of their total silver loads. Measurements of total
      silver as a function of time, by inductively coupled plasma mass spectrometry
      (ICP-MS), indicated that the silver was transferred from the water column and
      accumulated in the estuarine biota, including hard clams, grass shrimp, mud
      snails, cordgrass stalks and leaves, biofilms, intertidal sediment, and sand. The
      ICP-MS results and calculations of bioconcentration and trophic transfer factors
      indicated that significant amounts of silver were taken up by the organisms
      through trophic transfer. Silver was also adsorbed from the seawater into the
      biofilms, sediment, and sand, and from the sand into the clams.

PMID- 22369865
TI  - Correlation of tetracycline and sulfonamide antibiotics with corresponding
      resistance genes and resistant bacteria in a conventional municipal wastewater
      treatment plant.
AB  - Antibiotics and corresponding resistance genes and resistant bacteria have been
      considered as emerging pollutants worldwide. Wastewater treatment plants (WWTPs)
      are potential reservoirs contributing to the evolution and spread of antibiotic
      resistance. In this study, total concentrations of tetracycline and sulfonamide
      antibiotics in final effluent were detected at 652.6 and 261.1ng/L, respectively,
      and in treated sludge, concentrations were at 1150.0 and 76.0MUg/kg dry weight
      (dw), respectively. The quantities of antibiotic resistance genes and antibiotic
      resistant bacteria in final effluent were quantified in the range of 9.12*10(5)
      1.05*10(6) gene abundances /100mL (genomic copies/100mL) and 1.05*10(1)
      3.09*10(3)CFU/mL, respectively. In treated sludge, they were quantified at
      concentrations of 1.00*10(8)-1.78*10(9) gene abandances/100mL and 7.08*10(6)
      1.91*10(8)CFU/100mL, respectively. Significant reductions (2-3 logs, p<0.05) of
      antibiotic resistance genes and antibiotic resistant bacteria were observed
      between raw influent and final effluent. The gene abundances of tetO and tetW
      normalized to that of 16S rRNA genes indicated an apparent decrease as compared
      to sulI genes, which remained stable along each treatment stage. Significant
      correlations (R(2)=0.75-0.83, p<0.05) between numbers of resistant bacteria and
      antibiotic concentrations were observed in raw influent and final effluent. No
      significance (R(2)=0.15, p>0.05) was found between tet genes (tetO and tetW) with
      concentration of tetracyclines identified in wastewater, while a significant
      correlation (R(2)=0.97, p<0.05) was observed for sulI gene and total
      concentration of sulfonamides. Correlations of the quantities of antibiotic
      resistance genes and antibiotic resistant bacteria with corresponding
      concentrations of antibiotics in sludge samples were found to be considerably
      weak (R(2)=0.003-0.07).

PMID- 22369866
TI  - Short-term effect of humid airflow on antimicrobial air filters using Sophora
      flavescens nanoparticles.
AB  - Bioaerosols have received social and scientific attention because they can be
      hazardous to human health. Recently, antimicrobial treatments using natural
      products have been used to improve indoor air quality (IAQ) since they are
      typically less toxic to humans compared to other antimicrobial substances such as
      silver, carbon nanotubes, and metal oxides. Few studies, however, have examined
      how environmental conditions such as the relative humidity (RH), surrounding
      temperature, and retention time of bacteria on filters affect the filtration and
      antimicrobial characteristics of a filter treated with such natural products. In
      this study, we investigated changes in the morphology of the natural
      nanoparticles, pressure drop, filtration efficiency, and the inactivation rate
      caused by the short-term effect of humid airflow on antimicrobial fiber filters.
      Nanoparticles of Sophora flavescens were deposited on the filter media surface
      using an aerosol process. We observed coalescence and morphological changes of
      the nanoparticles on fiber filters under humid conditions of an RH >50%. The
      level of coalescence in these nanoparticles increased with increasing RH. Filters
      exposed to an RH of 25% have a higher pressure drop than those exposed to an RH
      >50%. In an inactivation test against Staphylococcus epidermidis bacterial
      aerosol, the inactivation efficiency at an RH of 25% was higher than that at an
      RH of 57% or 82%. To effectively apply antimicrobial filters using natural
      products in the environment, one must characterize the filters under various
      environmental conditions. Thus, this study provides important information on the
      use of antimicrobial filters made of natural products.

PMID- 22369867
TI  - Cyanotoxins in desert environments may present a risk to human health.
AB  - There have been few studies concerning cyanotoxins in desert environments,
      compared with the multitude of studies of cyanotoxins in aquatic environments.
      However, cyanobacteria are important primary producers in desert environments,
      where after seasonal rains they can grow rapidly both stabilising and fertilising
      arid habitats. Samples of cyanobacteria from wadis - dry, ephemeral river beds -
      and sabkha - supertidal salt flats - in Qatar were analysed for the presence of
      microcystins, nodularin, anatoxin-a, cylindrospermopsin and anatoxin-a(S).
      Microcystins were detected by HPLC-PDA and ELISA at concentrations between 1.5
      and 53.7ngg(-1) dry wt of crust. PCR products for the mycD gene for microcystin
      biosynthesis were detected after amplification of DNA from desert crust samples
      at two out of three sample sites. The presence of anatoxin-a(S) was also
      indicated by acetylcholine esterase inhibition assay. As a function of area of
      desert crust, microcystin concentrations were between 3 and 56MUgm(-2). Based on
      the concentration of microcystins detected in crust, with reference to the
      published inhalation NOAEL and LOAEL values via nasal spray inhalation of
      purified microcystin-LR in aqueous solution, and the amount of dust potentially
      inhaled by a person from these dried crusts, the dose of microcystins could
      exceed a calculated TDI value of 1-2ngkg(-1)day(-1) for an average adult. The
      presence of microcystins, and potentially of anatoxin-a(S), in desert crusts has
      important implications for human health. Further studies are required to monitor
      desert dust storms for the presence of cyanotoxins. An understanding of the risks
      of inhaling particles containing cyanotoxins is also warranted.

PMID- 22369868
TI  - Influences of beta-HCG administration on carbon isotope ratios of endogenous
      urinary steroids.
AB  - Several factors influencing the carbon isotope ratios (CIR) of endogenous urinary
      steroids have been identified in recent years. One of these should be the
      metabolism of steroids inside the body involving numerous different enzymes. A
      detailed look at this metabolism taking into account differences found between
      steroids excreted as glucuronides or as sulphates and hydrogen isotope ratios of
      different steroids pointed out possibility of unequal CIR at the main production
      sites inside the male body - the testes and the adrenal glands. By administration
      of beta-HCG it is possible to strongly stimulate the steroid production within
      the testes without influencing the production at the adrenal glands. Therefore,
      this treatment should result in changed CIR of urinary androgens in contrast to
      the undisturbed pre-treatment values. Four male volunteers received three
      injections of beta-HCG over a time course of 5 days and collected their urine
      samples at defined intervals after the last administration. Those samples showing
      the largest response in contrast to the pre-administration urines were identified
      by steroid profile measurements and subsequent analysed by GC/C/IRMS. CIR of
      androsterone, etiocholanolone, testosterone, 5alpha- and 5beta-androstanediol and
      pregnanediol were compared. While pregnanediol was not influenced, most of the
      investigated androgens showed depleted values after treatment. The majority of
      differences were found to be statistically significant and nearly all showed the
      expected trend towards more depleted delta(13)C-values. These results support the
      hypothesis of different CIR at different production sites inside the human body.
      The impact of these findings on doping control analysis will be discussed.

PMID- 22369869
TI  - Optical spectroscopy study of damage induced in 4H-SiC by swift heavy ion
      irradiation.
AB  - Single crystals of 4H-SiC were irradiated with swift heavy ions (332 MeV Ti, 106
      MeV Pb and 2.7 GeV U) in the electronic energy loss regime. The resulting damage
      was investigated with UV-visible optical absorption spectroscopy and micro-Raman
      spectroscopy. The evolution of the Raman data with fluence shows an accumulation
      of isolated point defects without amorphization of the material and a partial
      recrystallization of the structure, but only at the lowest fluence. Furthermore,
      the longitudinal optical phonon-plasmon coupling mode disappears upon
      irradiation, suggesting a strong perturbation of the electronic structure. This
      evolution is consistent with the optical bandgap decrease and the Urbach edge
      broadening that was also previously observed for the irradiation with 4 MeV Au
      ions.

PMID- 22369870
TI  - High spatial resolution Kelvin probe force microscopy with coaxial probes.
AB  - Kelvin probe force microscopy (KPFM) is a widely used technique to measure the
      local contact potential difference (CPD) between an AFM probe and the sample
      surface via the electrostatic force. The spatial resolution of KPFM is
      intrinsically limited by the long range of the electrostatic interaction, which
      includes contributions from the macroscopic cantilever and the conical tip. Here,
      we present coaxial AFM probes in which the cantilever and cone are shielded by a
      conducting shell, confining the tip-sample electrostatic interaction to a small
      region near the end of the tip. We have developed a technique to measure the true
      CPD despite the presence of the shell electrode. We find that the behavior of
      these probes agrees with an electrostatic model of the force, and we observe a
      factor of five improvement in spatial resolution relative to unshielded probes.
      Our discussion centers on KPFM, but the field confinement offered by these probes
      may improve any variant of electrostatic force microscopy.

PMID- 22369871
TI  - Workshop: combined exposure to chemicals.

PMID- 22369872
TI  - Oral bioaccessibility testing and read-across hazard assessment of nickel
      compounds.
AB  - In vitro metal ion bioaccessibility, as a measure of bioavailability, can be used
      to read-across toxicity information from data-rich, source substances to data
      poor, target substances. To meet the data requirements for oral systemic toxicity
      endpoints under the REACH Regulation in Europe, 12 nickel substances underwent
      bioaccessibility testing in stomach and intestinal fluids. A read-across paradigm
      was developed based on the correlation between gastric bioaccessibility and in
      vivo acute oral toxicity. The oral LD50 values were well predicted by nickel
      release (R2 = 0.91). Samples releasing <48% available nickel (mgNi released/mg
      available Ni * 100) are predicted to have an LD50 > 2000 mg/kg; while samples
      releasing > 76% available nickel are expected to have an LD50 between 300 and
      2000 mg/kg. The hazard classifications (European Regulation on Classification,
      Labelling and Packaging of Chemical Substances and Mixtures) for all oral
      systemic endpoints were evaluated based on read-across from three source nickel
      compounds (sulfate, subsulfide, oxide). Samples releasing < 48% available nickel
      were read-across from nickel oxides and subsulfide. Samples releasing > 76% Ni
      were read-across from nickel sulfate. This assessment suggests that nickel
      chloride and dihydroxide should be less stringently classified and nickel
      sulfamate should receive a more stringent classification for oral systemic
      endpoints than currently assigned.

PMID- 22369873
TI  - Application of computational toxicological approaches in human health risk
      assessment. I. A tiered surrogate approach.
AB  - Hazard identification and dose-response assessment for chemicals of concern found
      in various environmental media are typically based on epidemiological and/or
      animal toxicity data. However, human health risk assessments are often requested
      for many compounds found at contaminated sites throughout the US that have
      limited or no available toxicity information from either humans or animals. To
      address this issue, recent efforts have focused on expanding the use of structure
      activity relationships (SAR) approaches to identify appropriate surrogates and/or
      predict toxicological phenotype(s) and associated adverse effect levels. A tiered
      surrogate approach (i.e., decision tree) based on three main types of surrogates
      (structural, metabolic, and toxicity-like) has been developed. To select the
      final surrogate chemical and its surrogate toxicity value(s), a weight-of
      evidence approach based on the proposed decision tree is applied. In addition, a
      case study with actual toxicity data serves as the evaluation to support our
      tiered surrogate approach. Future work will include case studies demonstrating
      the utility of the surrogate approach under different scenarios for data-poor
      chemicals. In conclusion, our surrogate approach provides a reasonable starting
      point for identifying potential toxic effects, target organs, and/or modes-of
      action, and for selecting surrogate chemicals from which to derive either
      reference or risk values.

PMID- 22369874
TI  - Combining immunofluorescence and electron microscopy with quantum dots.

PMID- 22369875
TI  - Development and validation of the system of quality of life instruments for
      cancer patients: head and neck cancer (QLICP-HN).
AB  - Quality of life for patients with head and neck is now concerned worldwide, but
      the available QOL instruments are seldom and lack of Chinese culture. Therefore,
      this paper aimed to develop and validate a QOL instrument for patients with head
      and neck cancer, QLICP-HN. Using the programmed decision methods and the theory
      in instrument development, the QLICP-HN was developed and evaluated based on the
      data measuring QOL three times before and after treatment from a sample of 133 in
      patients of head and neck cancer. The psychometric properties of the scale were
      evaluated by indicators such as validity and reliability coefficients: Cronbach
      alpha, Pearson r, standardized response mean. The statistical methods included
      Pearson correlation, multi-trait scaling analysis, factor analysis, cluster
      analysis and paired t test. The internal consistency alpha for the overall scale
      and domains is above 0.70 with the exception of the social function (0.65) and
      common symptom and side effect (0.66); the test-retest reliability for each
      domain and the overall scale is higher than 0.80; most correlation coefficients
      between each item and its domain are above 0.40; the scores differences between
      pre-treatment and post-treatment have statistical significance for three domains
      of physical, psychological, the specific, and the overall instrument, with higher
      SRM of 0.33, 0.59, 0.44 and 0.53. The QLICP-HN is of good validity, reliability
      and responsiveness, and can be used to assess quality of life for patients with
      head and neck cancer in China.

PMID- 22369876
TI  - "Plastic Consumation" [sic] and the "search for surgical truth".

PMID- 22369877
TI  - Variogram-based fault diagnosis in an interconnected tank system.
AB  - We consider in this paper the fault diagnosis problem of a three tank system DTS
      200 pilot plant. The presented approach is based on the analysis of the
      variogram, which is a graphical variance representation that characterizes the
      distribution of a measured dataset, and is used to extract the sensor fault
      parameters. These parameters are obtained by determining the best mathematical
      model that fits the empirical data. Nonlinear regression techniques are used to
      estimate the model coefficients. Experimental study is provided to illustrate the
      potential applicability of this method in process monitoring.

PMID- 22369878
TI  - A novel practical control approach for rate independent hysteretic systems.
AB  - A disturbance rejection based control approach, active disturbance rejection
      control (ADRC), is proposed for hysteretic systems with unknown characteristics.
      It is an appealing alternative to hysteresis compensation because it does not
      require a detailed model of hysteresis, by treating the nonlinear hysteresis as a
      common disturbance and actively rejecting it. The stability characteristic of the
      ADRC is analyzed. It is shown that, in the face of the inherent dynamic
      uncertainties, the estimation and closed-loop tracking errors of ADRC are
      bounded, with their bounds monotonously decreasing with the observer and
      controller bandwidths, respectively. Simulation results on a typical hysteretic
      system further demonstrate the effectiveness of the proposed approach.

PMID- 22369879
TI  - Application of different methods to formulate PEG-liposomes of oxaliplatin:
      evaluation in vitro and in vivo.
AB  - In this work, the Film Method (FM), Reverse-Phase Evaporation (REV), and the
      Heating Method (HM) were applied to prepare PEG-coated liposomes of oxaliplatin
      with natural neutral and cationic lipids, respectively. The formulations
      developed with the three methods, showed similar physicochemical characteristics,
      except in the loading of oxaliplatin, which was statistically lower (P<0.05)
      using the HM. The incorporation of a semi-synthetic lipid in the formulation
      developed by FM, provided liposomes with a particle size of 115 nm associated
      with the lowest polydispersity index and the highest drug loading, 35%, compared
      with the other two lipids, suggesting an increase in the membrane stability. That
      stability was also evaluated according to the presence of cholesterol, the impact
      of the temperature, and the application of different cryoprotectants during the
      lyophilization. The results indicated long-term stability of the developed
      formulation, because after its intravenous in vivo administration to HT-29 tumor
      bearing mice was able to induce an inhibition of tumor growth statistically
      higher (P<0.05) than the inhibition caused by the free drug. In conclusion, the
      FM was the simplest method in comparison with REV and HM to develop in vivo
      stable and efficient PEG-coated liposomes of oxaliplatin with a loading higher
      than those reported for REV.

PMID- 22369880
TI  - Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes
      containing bile salts in rats: the effect of cholate type, particle size and
      administered dose.
AB  - Oral delivery of protein or polypeptide drugs remains a challenge due to gastric
      and enzymatic degradation as well as poor permeation across the intestinal
      epithelia. In this study, liposomes containing bile salts were developed as a new
      oral insulin delivery system. The primary goal was to investigate the effect of
      cholate type, particle size and dosage of the liposomes on the hypoglycemic
      activity and oral bioavailability. Liposomes containing sodium glycocholate
      (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a
      reversed-phase evaporation method. After oral administration, all liposomes
      elicited a certain degree of hypoglycemic effect in parallel with an increase in
      blood insulin level. The highest oral bioavailability of approximately 8.5% and
      11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes
      in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed
      slower and sustained action over a period of over 20 h with peak time around 8
      12h. SGC-liposomes showed higher oral bioavailability than liposomes containing
      STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent
      with the highest at 150 nm or 400 nm and was proportionally correlated to the
      administered dose. The results supported the hypothesis of insulin absorption as
      intact liposomes.

PMID- 22369881
TI  - Targeting megalin to enhance delivery of anti-clusterin small-interfering RNA
      nanomedicine to chemo-treated breast cancer.
AB  - The goal of this study is to evaluate a new targeting strategy to improve
      nanomedicine delivery to breast cancer cells that survive prior exposure to
      chemotherapy. These cells are particularly difficult to treat because they often
      develop drug resistance by upregulation of chemoresistant factors such as
      clusterin and should be preferably eradicated before they further spread out. In
      this study, the surface endocytotic receptor megalin was studied for the first
      time for targeted delivery of anti-clusterin small-interfering RNAs (siRNAs) to
      these chemo-treated cells. Lipid-polyethylenimine hybrid nanocarriers decorated
      with apolipoprotein E (Ap-LPNs) were developed for this purpose. Using
      immunoblotting, we demonstrated induction of both megalin and clusterin in MCF-7
      cells by previous paclitaxel treatment. The siRNA transfection of these megalin
      rich chemo-treated cancer cells was improved by three-fold when the siRNAs were
      delivered by Ap-LPNs. This trend was translatable into enhanced clusterin
      knockdown and improved chemosensitization to subsequent paclitaxel treatment
      (both p<0.05 versus uncoated LPNs). This proof-of-principle study has validated a
      novel "chemoresistance-targeting" strategy for siRNA delivery to the cancer cell
      subpopulation that begins to acquire chemoresistance and is in strong need for
      chemosensitization.

PMID- 22369882
TI  - The fungicide mancozeb induces toxic effects on mammalian granulosa cells.
AB  - The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low
      reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects
      oocyte meiotic spindle morphology and impairs fertilization rate even when used
      at very low concentrations. We evaluated the toxic effects of mancozeb on the
      mouse and human ovarian somatic granulosa cells. We examined parameters such as
      cell morphology, induction of apoptosis, and p53 expression levels. Mouse
      granulosa cells exposed to mancozeb underwent a time- and dose-dependent
      modification of their morphology, and acquired the ability to migrate but not to
      proliferate. The expression level of p53, in terms of mRNA and protein content,
      decreased significantly in comparison with unexposed cells, but no change in
      apoptosis was recorded. Toxic effects could be attributed, at least in part, to
      the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was
      found in culture medium. Human granulosa cells also showed dose-dependent
      morphological changes and reduced p53 expression levels after exposure to
      mancozeb. Altogether, these results indicate that mancozeb affects the somatic
      cells of the mammalian ovarian follicles by inducing a premalignant-like status,
      and that such damage occurs to the same extent in both mouse and human GC. These
      results further substantiate the concept that mancozeb should be regarded as a
      reproductive toxicant.

PMID- 22369883
TI  - Baicalein inhibits pulmonary carcinogenesis-associated inflammation and
      interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo.
AB  - The objective of the present study is to investigate the therapeutic efficacy of
      baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion
      factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50mg/kg
      body weight) induced pulmonary carcinogenesis in Swiss albino mice. After
      experimental period, increased levels of total and differential cell count in
      bronchoalveolar lavage fluid were observed. Accompanied by marked increase in
      immature mast cell by toluidine blue staining and mature mast cell by safranin
      alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein
      expression levels studied by immunohistochemistry and immunoblot analysis of
      cytokines such as tumor necrosis factor-alpha, interleukin-1beta and inducible
      nitric oxide synthase were also found to be significantly increased in lung
      cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of
      nuclear transcription factor kappa-B as confirmed by immunofluorescence and
      immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly
      counteracted all the above deleterious changes. Moreover, assessment of tumor
      invasion factors on protein levels by immunoblot and mRNA expression levels by RT
      PCR revealed that BE treatment effectively negates B(a)P-induced upregulated
      expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo
      oxygenase-2. Further analysis of lipid peroxidation markers such as
      thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as
      glutathione-S-transferase and reduced glutathione in lung tissue was carried out
      to substantiate the antioxidant effect of BE. The chemotherapeutic effect
      observed in the present study is attributed to the potent anti-inflammatory and
      antioxidant potential by BE against pulmonary carcinogenesis.

PMID- 22369884
TI  - Growth and relaxation processes in Ge nanocrystals on free-standing Si(001)
      nanopillars.
AB  - We study the growth and relaxation processes of Ge crystals selectively grown by
      chemical vapour deposition on free-standing 90 nm wide Si(001) nanopillars. Epi
      Ge with thickness ranging from 4 to 80 nm was characterized by synchrotron based
      x-ray diffraction and transmission electron microscopy. We found that the strain
      in Ge nanostructures is plastically released by nucleation of misfit
      dislocations, leading to degrees of relaxation ranging from 50 to 100%. The
      growth of Ge nanocrystals follows the equilibrium crystal shape terminated by low
      surface energy (001) and {113} facets. Although the volumes of Ge nanocrystals
      are homogeneous, their shape is not uniform and the crystal quality is limited by
      volume defects on {111} planes. This is not the case for the Ge/Si nanostructures
      subjected to thermal treatment. Here, improved structure quality together with
      high levels of uniformity of the size and shape is observed.

PMID- 22369885
TI  - DNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA
      replication and repair of oxidative lesions.
AB  - Specific DNA repair pathways from Trypanosoma cruzi are believed to protect
      genomic DNA and kinetoplast DNA (kDNA) from mutations. Particular pathways are
      supposed to operate in order to repair nucleotides oxidized by reactive oxygen
      species (ROS) during parasite infection, being 7,8-dihydro-8-oxoguanine (8oxoG) a
      frequent and highly mutagenic base alteration. If unrepaired, 8oxoG can lead to
      cytotoxic base transversions during DNA replication. In mammals, DNA polymerase
      beta (Polbeta) is mainly involved in base excision repair (BER) of oxidative
      damage. However its biological role in T. cruzi is still unknown. We show, by
      immunofluorescence localization, that T. cruzi DNA polymerase beta (Tcpolbeta) is
      restricted to the antipodal sites of kDNA in replicative epimastigote and
      amastigote developmental stages, being strictly localized to kDNA antipodal sites
      between G1/S and early G2 phase in replicative epimastigotes. Nevertheless, this
      polymerase was detected inside the mitochondrial matrix of trypomastigote forms,
      which are not able to replicate in culture. Parasites over expressing Tcpolbeta
      showed reduced levels of 8oxoG in kDNA and an increased survival after treatment
      with hydrogen peroxide when compared to control cells. However, this resistance
      was lost after treating Tcpolbeta overexpressors with methoxiamine, a potent BER
      inhibitor. Curiously, a presumed DNA repair focus containing Tcpolbeta was
      identified in the vicinity of kDNA of cultured wild type epimastigotes after
      treatment with hydrogen peroxide. Taken together our data suggest participation
      of Tcpolbeta during kDNA replication and repair of oxidative DNA damage induced
      by genotoxic stress in this organelle.

PMID- 22369886
TI  - Influence of polyphenols on allergic immune reactions: mechanisms of action.
AB  - The increased incidence of allergic disease seems to rely on many factors. Among
      them, the association between genetic variations of the immune response and
      environmental pressure by allergens, infectious agents and pollutants should be
      taken into consideration. In alternative to conventional treatments with
      corticosteroids and antihistaminics, nutraceuticals have been shown to act on
      allergic disease either during allergic sensitisation or on consolidated disease.
      In this review, special emphasis is placed on the effects of dietary polyphenols
      on three major allergic diseases, namely atopic eczema, food allergy and asthma.
      Interference of polyphenols with T-helper 2 activation seems to be the main
      mechanism of their inhibitory effects on allergy development. Moreover, deficits
      of T-regulatory cells seem to play a pathogenic role in allergic disease and,
      therefore, these cells may represent a major target of polyphenol activity.

PMID- 22369887
TI  - Pulmonary zygomycosis in a non-neutropenic patient with myelodysplastic syndrome
      on lenalidomide.
AB  - Pulmonary zygomycosis is an uncommon infection that occurs mostly in
      immunocompromised patients. We report the case of a 75-year-old man with
      myelodysplastic syndrome, treated with lenalidomide for 3 months, who developed
      respiratory failure and a rapidly progressive left upper lobe  consolidation. An
      extensive workup was unrevealing of the etiology, and the patient expired. A full
      autopsy was declined, but an in situ post-mortem transbronchial lung biopsy
      revealed pulmonary zygomycosis. This unique case illustrates the potential risks
      of lenalidomide therapy in patients  with myelodysplastic syndrome and the
      difficulties in diagnosing pulmonary zygomycosis. To our knowledge this is the
      first report of a diagnostic in situ post-mortem transbronchial lung biopsy.

PMID- 22369890
TI  - Temperature-dependent electrical, elastic and magnetic properties of sol-gel
      synthesized Bi(0.9)Ln(0.1)FeO3 (Ln = Nd, Sm).
AB  - This report details correlated electrical, mechanical and magnetic behaviour in
      BiFeO(3) ceramics doped with 10% Ln (Ln = Sm, Nd) ions on the Bi, or perovskite
      A, site and synthesized by a sol-gel method. The ceramics exhibit bulk
      piezoelectric and ferroelectric properties and clear ferroelectric domain
      patterns through piezoresponse force microscopy. Resonant ultrasound
      spectroscopy, dielectric spectroscopy and magnetometry studies show correlated
      magnetoelectromechanical behaviour and the existence of weak ferromagnetism for
      both compositions. An anomaly with simultaneous mechanical and magnetic
      signatures is discovered in both materials near room temperature, while
      previously reported transitions and anomalies are found to exhibit electro-
      and/or magnetomechanical coupling. Magnetism is significantly enhanced in the Sm
      doped sample, which is a promising multiferroic material.

PMID- 22369888
TI  - Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number
      variants distributed in diverse yeast strains from differing industrial
      environments.
AB  - Although the budding yeast Saccharomyces cerevisiae is arguably one of the most
      well-studied organisms on earth, the genome-wide variation within this species-
      i.e., its "pan-genome"--has been less explored. We created a multispecies
      microarray platform containing probes covering the genomes of several
      Saccharomyces species: S. cerevisiae, including regions not found in the standard
      laboratory S288c strain, as well as the mitochondrial and 2-MUm circle genomes
      plus S. paradoxus, S. mikatae, S. kudriavzevii, S. uvarum, S. kluyveri, and S.
      castellii. We performed array-Comparative Genomic Hybridization (aCGH) on 83
      different S. cerevisiae strains collected across a wide range of habitats; of
      these, 69 were commercial wine strains, while the remaining 14 were from a
      diverse set of other industrial and natural environments. We observed
      interspecific hybridization events, introgression events, and pervasive copy
      number variation (CNV) in all but a few of the strains. These CNVs were
      distributed throughout the strains such that they did not produce any clear
      phylogeny, suggesting extensive mating in both industrial and wild strains. To
      validate our results and to determine whether apparently similar introgressions
      and CNVs were identical by descent or recurrent, we also performed whole-genome
      sequencing on nine of these strains. These data may help pinpoint genomic regions
      involved in adaptation to different industrial milieus, as well as shed light on
      the course of domestication of S. cerevisiae.

PMID- 22369889
TI  - Genome-wide determination of RNA stability reveals hundreds of short-lived
      noncoding transcripts in mammals.
AB  - Mammalian genomes produce huge numbers of noncoding RNAs (ncRNAs). However, the
      functions of most ncRNAs are unclear, and novel techniques that can distinguish
      functional ncRNAs are needed. Studies of mRNAs have revealed that the half-life
      of each mRNA is closely related to its physiological function, raising the
      possibility that the RNA stability of an ncRNA reflects its function. In this
      study, we first determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa
      Tet-off (TO) cells by developing a novel genome-wide method, which we named 5'
      bromo-uridine immunoprecipitation chase-deep sequencing analysis (BRIC-seq). This
      method involved pulse-labeling endogenous RNAs with 5'-bromo-uridine and
      measuring the ongoing decrease in RNA levels over time using multifaceted deep
      sequencing. By analyzing the relationship between RNA half-lives and functional
      categories, we found that RNAs with a long half-life (t(1/2) >= 4 h) contained a
      significant proportion of ncRNAs, as well as mRNAs involved in housekeeping
      functions, whereas RNAs with a short half-life (t(1/2) < 4 h) included known
      regulatory ncRNAs and regulatory mRNAs. The stabilities of a significant set of
      short-lived ncRNAs are regulated by external stimuli, such as retinoic acid
      treatment. In particular, we identified and characterized several novel long
      ncRNAs involved in cell proliferation from the group of short-lived ncRNAs. We
      designated this novel class of ncRNAs with a short half-life as Short-Lived
      noncoding Transcripts (SLiTs). We propose that the strategy of monitoring RNA
      half-life will provide a powerful tool for investigating hitherto functionally
      uncharacterized regulatory RNAs.

PMID- 22369891
TI  - Highly selective capture of phosphopeptides using a nano titanium dioxide
      multiwalled carbon nanotube nanocomposite.
AB  - In this study, a titanium dioxide-multiwalled carbon nanotube (TiO2-MWNT)
      nanocomposite was first used to enrich phosphopeptides as a binding agent. The
      TiO2-MWNT nanocomposite was synthesized by the hydrothermal reaction process and
      characterized by transmission electron microscopy (TEM), Fourier transform
      infrared (FTIR), and X-ray powder diffraction (XRD). The results demonstrated
      that the anatase phase TiO2 nanoparticles had been successfully linked by MWNTs.
      The TiO2-MWNT nanocomposite was applied as a sorbent to enrich phosphopeptides,
      and the results showed that the performance of the TiO2-MWNT nanocomposite was
      better than 5 MUm TiO2, as confirmed by the analysis of phosphopeptides from a
      tryptic digest of a standard protein (beta-casein and bovine serum albumin) using
      high-performance liquid chromatography-electrospray ionization-mass spectrometry
      (HPLC-ESI-MS). The use of lactic acid in the loading buffer significantly
      enhances the selectivity of the TiO2-MWNT nanocomposite. This nanocomposite
      material was further applied to enrich the phosphopeptides in a protein digest
      obtained from nonfat milk successfully.

PMID- 22369892
TI  - Analysis of sphingolipids in extracted human plasma using liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - We have developed an analytical method used to quantify sphingolipids, including
      deoxysphingoid bases, in lipid extracts prepared from human plasma. In total, 39
      analytes were identified and analyzed in a single chromatographic run in less
      than 5 min. The new method is 4-8 times faster and more sensitive than previously
      published methods. We also describe a simple sample preparation method that
      allows medium-throughput screening of human plasma samples. Mass spectrometric
      analyses were performed online using liquid chromatography electrospray
      ionization tandem mass spectrometry (LC-ESI-MS/MS) in the positive multiple
      reaction monitoring mode. Samples were extracted using a one-phase extraction
      method (methanol-dichloromethane) with appropriate internal standards.
      Sphingolipid analytes were linear over a wide range of concentrations, from 0.01
      to 50 ng/ml, with a high correlation coefficient (r2 = 0.999). We successfully
      applied this method to analyze the levels of sphingolipid metabolites in healthy
      human plasma. The ceramide, dihydroceramide, hexosylceramide, and GM3 levels
      observed in females were slightly higher than those observed in males.

PMID- 22369893
TI  - Fluorescence detection of adenosine triphosphate through an aptamer-molecular
      beacon multiple probe.
AB  - An aptamer-molecular beacon (MB) multiple fluorescent probe for adenosine
      triphosphate (ATP) assay is proposed in this article. The ATP aptamer was used as
      a molecular recognition part, and an oligonucleotide (short strand, SS) partially
      complementary with the aptamer and an MB was used as the other part. In the
      presence of ATP, the aptamer bound with it, accompanied by the hybridization of
      MB and SS and the fluorescence recovering. Wherever there is only very weak
      fluorescence can be measured in the absence of ATP. Based on the relationship of
      recovering fluorescence and the concentration of ATP, a method for quantifying
      ATP has been developed. The fluorescence intensity was proportional to the
      concentration of ATP in the range of 10 to 500 nM with a detection limit of 0.1
      nM. Moreover, this method was able to detect ATP with high selectivity in the
      presence of guanosine triphosphate (GTP), cytidine triphosphate (CTP), and
      uridine triphosphate (UTP). This method is proved to be simple with high
      sensitivity, selectivity, and specificity.

PMID- 22369894
TI  - Detection of N-glycans on small amounts of glycoproteins in tissue samples and
      sodium dodecyl sulfate-polyacrylamide gels.
AB  - N-linked glycans harbored on glycoproteins profoundly affect the character of
      proteins by altering their structure or capacity to bind to other molecules.
      Specific knowledge of the role of N-glycans in these changes is limited due to
      difficulties in identifying precise carbohydrate structures on a given
      glycoprotein, which arises from the large amounts of glycoprotein required for N
      glycan structural determination. Here, we refined a simple method to purify and
      detect trace amounts of N-glycans. During the N-glycan purification step, most
      contaminants were removed by two kinds of columns: a graphite carbon column and a
      cellulose column. N-Glycans were identified with a three-dimensional high
      performance liquid chromatography (HPLC) system. Using our method, a global
      analysis of N-glycans from human muscle biopsy samples and mouse brain sections
      was possible. By combining sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) with our method, we refined analytical procedures for
      N-glycans from SDS-PAGE gels using hydrazinolysis to achieve a high N-glycan
      recovery rate. N-Glycans on as little as 1 MUg of the target protein transferrin
      or immunoglobulin G (IgG) were easily detected. These methods allowed us to
      efficiently determine glycoprotein N-glycans at picomole (pmol) levels.

PMID- 22369896
TI  - Selection of DNA aptamers against polychlorinated biphenyls as potential
      biorecognition elements for environmental analysis.
AB  - Polychlorinated biphenyls (PCBs) have been of major concerns for decades due to
      their potential toxicity to human health. To trace the PCBs efficiently and
      sensitively, many detection methods have been developed. Aptamers, a new class of
      diagnostic tools, are considered to be such additional candidates for detection
      of pollutants. In the current study, we report the DNA aptamers, isolated by
      FluMag-SELEX (a modified SELEX [systematic evolution of ligands by exponential
      enrichment] technology), that recognize PCBs with the dissociation constants (Kd
      values) down to the micromolar range. Using the selected aptamers, a highly
      sensitive aptamer-based fluorescent assay for detection of PCBs was established
      using gold nanoparticles, with a widely linear range from 0.1 to 100 ng/ml.
      Moreover, our aptamer-based gold nanoprobe displays specificity toward 3,3',4,4'
      tetrachlorobiphenyl (PCB77) compared with a few common PCB77 structural analogs.
      These results open the possibility of using aptamers as biorecognition elements
      for easy and fast environmental monitoring.

PMID- 22369895
TI  - Accurate quantitation of phospholamban phosphorylation by immunoblot.
AB  - We have developed a quantitative immunoblot method to measure the mole fraction
      of phospholamban (PLB) phosphorylated at Ser16 (X(p)) in biological samples. In
      cardiomyocytes, PLB phosphorylation activates the sarcoplasmic reticulum calcium
      ATPase (SERCA), which reduces cytoplasmic Ca(2+) to relax the heart during
      diastole. Unphosphorylated PLB (uPLB) inhibits SERCA at low [Ca(2+)] but
      phosphorylated PLB (pPLB) is less inhibitory, so myocardial physiology and
      pathology depend critically on X(p). Current methods of X(p) determination by
      immunoblot provide moderate precision but poor accuracy. We have solved this
      problem using purified uPLB and pPLB standards produced by solid-phase peptide
      synthesis. In each assay, a pair of blots is performed with identical standards
      and unknowns using antibodies partially selective for uPLB and pPLB,
      respectively. When performed on mixtures of uPLB and pPLB, the assay measures
      both total PLB (tPLB) and X(p) with accuracy of 96% or better. We assayed pig
      cardiac sarcoplasmic reticulum (SR) and found that X(p) varied widely among four
      animals, from 0.08 to 0.38, but there was remarkably little variation in the
      ratios of X(p)/tPLB and uPLB/SERCA, suggesting that PLB phosphorylation is tuned
      to maintain homeostasis in SERCA regulation.

PMID- 22369897
TI  - Surface plasmon resonance imaging biosensor for cathepsin G based on a potent
      inhibitor: development and applications.
AB  - A specific surface plasmon resonance imaging (SPRI) array biosensor for the
      determination of the enzymatically active cathepsin G (CatG) has been developed.
      For this purpose, a specific interaction between an inhibitor immobilized onto a
      chip surface and CatG in an analyzed solution was used. The MARS-115 CatG
      peptidyl inhibitor containing the 1-aminoalkylphosphonate diaryl ester moiety at
      the C terminus and N-succinamide with a free carboxylic function was synthesized
      and covalently immobilized onto the gold chip surface via the thiol group
      (cysteamine). Atomic force microscopy was used for the observation of surface
      changes during the subsequent steps of chip manufacture. Optimal detection
      conditions were chosen. High specificity of synthesized inhibitor to CatG was
      proved. The precision, as well as the accuracy, was found to be well suited to
      enzyme determination. The sensor application for the determination of CatG in
      white blood cells and saliva was shown for potential diagnosis of leukemia and
      oral cavity diseases during the early stages of those pathological states.

PMID- 22369898
TI  - Spectroscopic (FT-IR, FT-Raman, UV absorption, 1H and 13C NMR) and theoretical
      (in B3LYP/6-311++G** level) studies on alkali metal salts of caffeic acid.
AB  - The effect of some metals on the electronic system of benzoic and nicotinic acids
      has recently been investigated by IR, Raman and UV spectroscopy [1-3]. Benzoic
      and nicotinic acids are regarded model systems representing a wide group of
      aromatic ligands which are incorporated into enzymes. In this work the FT-IR (in
      solid state and in solution), FT-Raman, UV absorption and (1)H and (13)C NMR
      spectra of caffeic acid (3,4-dihydroxycinnamic acid) and its salts with lithium,
      sodium, potassium, rubidium and caesium were registered, assigned and analyzed.
      The effect of alkali metals on the electronic system of ligands was discussed.
      Studies of differences in the number and position of bands from the IR, Raman, UV
      absorption spectra and chemical shifts from NMR spectra allowed to conclude on
      the distribution of electronic charge in the molecules, the delocalization energy
      of pi electrons and the reactivity of ligands in metal complexes. Optimized
      geometrical structures of studied compounds were calculated by B3LYP method using
      6-311++G** basis set. Bond lengths, angles and dipole moments for the optimized
      structures of caffeic acid and lithium, sodium, potassium caffeinates were also
      calculated. The theoretical wavenumbers and intensities of IR spectra were
      obtained. The calculated parameters were compared to the experimental
      characteristics of investigated compounds. Microbial activity of studied
      compounds was tested against Escherichia coli, Pseudomonas aeruginosa,
      Staphylococcus aureus and Proteus vulgaris.

PMID- 22369899
TI  - Occurrence and distribution of Staphylococcus aureus lineages among zoo animals.

PMID- 22369900
TI  - Histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits anti
      inflammatory activities through induction of mitochondrial damage and apoptosis
      in activated lymphocytes.
AB  - Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been
      proven to be an anti-cancer agent. Its anti-inflammatory activities have recently
      been observed both in in vitro and in vivo models. Yet its action on lymphocytes
      and the underlying mechanism are still not well known. In this study, in order to
      evaluate the anti-inflammatory function of SAHA, we analyzed the effects of SAHA
      on the proliferation, activation, cytokines secretion, cell cycle distribution
      and apoptosis of murine lymphocytes activated with concanavalin A (Con A). Our
      results demonstrated that SAHA inhibited the proliferation of Con A-activated
      lymphocytes in a dose-dependent manner. The expression of CD69 on CD3(+) T
      lymphocytes was significantly inhibited by SAHA. Intracellular cytokine staining
      analysis showed that SAHA could downregulate the expression of pro-inflammatory
      cytokines TNF-alpha, IL-6 and IFN-gamma in T lymphocytes. Furthermore, analysis
      of sub-G(0)/G(1) peaks and annexin V binding populations revealed that SAHA
      induced apoptotic cell death in Con A-activated lymphocytes. Consistent with
      these results, SAHA treatment also induced a decrease of mitochondrial membrane
      potential and cleavage of caspase-3 and PARP in these cells. Moreover, SAHA
      caused an accumulation of phosphorylated histone H2A.X, indicating increased
      double strand DNA breaks. These findings suggest that induction of apoptosis
      through the mitochondrial pathway may contribute to the anti-inflammatory
      activities of SAHA on activated lymphocytes.

PMID- 22369901
TI  - [Implementation of new tonsillectomy method should involve cost-benefit
      analysis].

PMID- 22369902
TI  - [Access to medical education?].

PMID- 22369903
TI  - [Admission tests for medical education].
AB  - This state of the art article explores what is known from the international and
      Danish literature on admission criteria as predictors of success in medical
      education. Previous academic performance is the best known predictor of medical
      students' grades. Poorer entry qualifications, broadly defined, are associated
      with dropout in medical education. Admission interviews may have a small additive
      explanatory effect on medical students' grades, but the effect on dropout has
      barely been investigated. Admission interviews are a challenge for the
      feasibility, reliability and validity of medical student selection. Admission
      variables in use should be supported by predictive validity.

PMID- 22369904
TI  - [Ethical consequences of the diagnosis of psychosis].
AB  - Psychosis is defined by the loss of reality testing. Apart from that, it is
      rather broadly and vaguely defined. Ethics is the art of defining what is right
      and what is wrong. Medical ethics apply a diversity of ethical principles to a
      complex clinical reality after discussion and consideration. In forensic
      psychiatry the diagnosis of psychosis has vast ethical implications. In the
      Danish law on psychiatry conditions for coercion and involuntary treatment are
      stated, and in the law on penalty the principle of treatment instead of penalty
      is stated. Thus, implications for diagnoses and treatment go far beyond other
      medical diagnoses.

PMID- 22369905
TI  - [Unsuccessful vitamin D treatment].
AB  - Vitamin D3 (25-OHD3) analyses have increased exponentially and vitamin D
      deficiency (< 25 nmol/l) is common (15% of patients). The aim of the paper is to
      discuss reasons for unsuccessful treatment and to question the use of
      ergocalciferol (vitamin D2). Lack of effect of treatment can be due to: 1) too
      low dose, 2) incorrect analytical methods when injection treatment (vitamin D2)
      is used, 3) obesity, 4) seasonal variations, and 5) poor compliance. Treatment is
      mandatory in order to prevent osteopenia and osteoporosis. Vitamin D3 is more
      potent than vitamin D2. Injections with vitamin D2 should be replaced by vitamin
      D3.

PMID- 22369906
TI  - [New knowledge of spasticity and its treatment].
AB  - Spasticity is a frequently used diagnosis, and anti-spastic medication is used
      widespread. In this systematic review article we highlight difficulties in
      diagnosing spasticity correctly and thus limit the value of the diagnosis in
      ensuring the best possible treatment. We review recent neuroscience research and
      conclude that it is necessary to develop better tools for clinical diagnosis of
      spasticity in order to avoid potential malpractice and to limit treatment with
      anti-spastic drugs for patients with documented increased reflex-mediated muscle
      tone as their main annoyance.

PMID- 22369907
TI  - [The quality of susceptibility examinations of urine in general practice is
      generally good].
AB  - In Denmark, many microbiological tests (microscopy, culture and susceptibility
      examinations) are done in general practice for the diagnosis of urinary tract
      infections (UTI). In 2006, the costs of susceptibility examinations were 28
      million DKK. Some regional health authorities have established a program for
      quality assessment. National quality requirements for susceptibility examinations
      have already been established. The clinical microbiological departments send
      simulated urines with bacteria of common UTI strains. The specimens are examined
      in general practice with routine methods. The results for a two-year period of
      susceptibility examinations are reported. Generally, the quality criteria were
      met.

PMID- 22369908
TI  - [Anti-thyroid antibodies in two patients with subacute dementia, ataxia, and
      myoclonus].
AB  - Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with
      anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both
      disorders can have a similar clinical presentation. Two women, 67 and 63 year
      old, with subacute dementia, ataxia, myoclonus and positive antithyroid
      antibodies were given oral steroids. Whereas one progressively declined and had
      histopathologically proven CJD, the other made a complete recovery and was
      diagnosed with HE. Anti-thyroid antibodies can occur in CJD, but when present in
      a patient with subacute dementia, ataxia and myoclonus, a steroid trial always
      seems indicated.

PMID- 22369909
TI  - [Suspected allergic reaction during anesthesia requires thorough postoperative
      investigation].
AB  - Allergic reactions during anaesthesia are rare and the cause is seldom
      immediately obvious. Incorrect guesses for the offending substance can lead to
      suboptimal management. Furthermore there is a risk of a serious reaction on
      subsequent exposure to the real allergen. We present a case of suspected allergy
      to fentanyl investigated at the Danish Anaesthesia Allergy Centre. Allergy to
      this drug could not be demonstrated by skin tests or challenge. The reaction was
      due to unspecific histamine release induced by several opioids given at the same
      time. Future pretreatment with antihistamine was recommended.

PMID- 22369910
TI  - [Aorta-caval fistula as a complication to abdominal aorta aneurysm].
AB  - An 84 year-old man with a history of mild well-controlled hypertension was
      admitted acute with severe chest and epigastrial pains, radiation to the back and
      nausea lasting one hour under the diagnosis acute coronary syndrome. Acute
      computed tomography of the thorax and abdomen showed an 8 x 10 cm infrarenal
      abdominal aorta aneurysm with a 10 mm fistula through the wall of the aorta into
      the inferior caval vein.

PMID- 22369911
TI  - PALLAS: insights into permanent atrial fibrillation.

PMID- 22369912
TI  - Prognosis value of central venous oxygen saturation in acute decompensated heart
      failure.
AB  - BACKGROUND: Central venous oxygen saturation (ScvO2) provides an estimation of
      body oxygen consumption/delivery ratio. Its use has been suggested for monitoring
      treatment of patients admitted for acute decompensated heart failure (ADHF) but
      the optimal target value has never been clearly reported. AIMS: We aimed to
      address the prognostic value of ScvO2 in ADHF requiring inotrope support.
      METHODS: ScvO2 was prospectively assessed in 60 patients with ADHF requiring
      inotrope support (mean age 62+/-16 years; 45 men; left ventricular ejection
      fraction 25+/-7%) and was compared with major adverse cardiac events (MACE),
      defined as heart transplantation, cardiac assistance and death. RESULTS: MACE
      occurred in 22 (35%) patients (14 deaths; eight referred for heart
      transplantation or cardiac assistance). Admission ScvO2 (mean 57+/-13%) did not
      differ between patients with and without MACE. At 24 hours ScvO2 (mean 62+/-7%)
      increased only in patients without MACE (65+/-6% vs. 58+/-7%; p<0.0001) and was
      associated with urine output, vena cava diameter and oxygen consumption
      reduction. No correlation was observed between ScvO2 and cardiac output or
      catecholamine rate. Multivariable analysis showed that ScvO2 at 24 hours remained
      an independent predictor of MACE. Using the optimal cut-off of 60% derived from
      receiver operating characteristic curves, MACE were observed in 81% of patients
      (17/21) with ScvO2<=60% at 24 hours vs. 13% (5/39) with ScvO2>60% at 24 hours.
      CONCLUSION: In patients admitted for ADHF requiring inotrope support, ScvO2<=60%
      despite optimal treatment is a marker of poor outcome and might be an indicator
      for considering more aggressive therapy.

PMID- 22369913
TI  - Aortic root dilatation in young patients with cryptogenic stroke and patent
      foramen ovale.
AB  - BACKGROUND: No previous study has looked for an association between aortic
      dilatation and the clinical sequelae of patent foramen ovale (PFO), although a
      possible relationship has been identified in case reports. AIM: To compare aortic
      dimensions in patients with symptomatic PFO and healthy controls. METHODS: Forty
      seven patients were identified who presented with cryptogenic cerebrovascular
      accident (CVA) assessed as most likely secondary to PFO (confirmed by contrast
      study), were aged less than 50 years and underwent percutaneous PFO closure.
      Forty-seven age-, sex- and body surface area-matched healthy controls were also
      identified. RESULTS: Aortic root diameters were greater in PFO patients. The
      difference was more marked at the levels of the sinuses of Valsalva (34+/-4 vs
      31+/-3 mm, P<0.01) and the proximal ascending aorta (32+/-4 vs 29+/-3, P<0.01)
      and more modest at the level of the aortic annulus (23+/-3 vs 22+/-2 mm, P=0.20).
      In addition, patients with massive right-to-left shunting tended to have larger
      aortic diameters. In contrast, left ventricular end-systolic and end-diastolic
      diameters were not larger than in controls (30+/-4 vs 32+/-5 mm, P=0.10 and 48+/
      5 vs 50+/-4 mm, P=0.04, respectively). CONCLUSION: The present study shows that
      aortic diameter is increased in young patients with cryptogenic CVA and PFO
      compared with in healthy subjects. Our results suggest that aortic dilatation may
      potentiate the risk of CVA in PFO patients and support further research in this
      area.

PMID- 22369914
TI  - Incidence, determinants and consequences of left atrial remodelling after a first
      anterior myocardial infarction.
AB  - BACKGROUND: Left atrial (LA) volume is an important predictor of mortality and
      morbidity after myocardial infarction (MI). However, the process of LA
      remodelling has not been extensively investigated. AIMS: Our purpose was to
      analyse the incidence, determinants and consequences of LA remodelling in a
      cohort of patients with a first anterior MI enrolled in the modern era of MI
      management. METHODS: We used data from 246 patients with a first anterior MI who
      were included in a prospective study on left ventricular (LV) remodelling (REVE
      2). Serial echocardiographic studies were performed before discharge and at 3
      months and 1 year after MI. RESULTS: LA volume increased from 20.5+/-5.9 mL/m2 at
      baseline to 24.6+/-7.4 mL/m2 at 3 months (P<0.0001 versus baseline) and 25.4+/
      7.6 mL/m2 at 1 year (P<0.0001 versus baseline). Patients with high LA volumes at
      baseline had higher LV volumes, decreased LV systolic function, increased E/Ea
      (early transmitral velocity/mitral annular early diastolic velocity ratio) and
      increased B-type natriuretic peptide concentration. By multivariable analysis,
      the sole independent predictor of change in LA volume from baseline to 1 year was
      peak creatine kinase concentration (P<0.0001). Patients with higher LA volumes at
      baseline were at higher risk of cardiovascular death or rehospitalization for
      heart failure during follow-up (P=0.015). CONCLUSIONS: Despite modern therapeutic
      management, LA remodelling is common during the first 3 months after anterior MI.
      Patients with larger infarct size are at greater risk of LA remodelling after
      discharge.

PMID- 22369915
TI  - Single-centre experience with an 8-mm tip catheter for radiofrequency catheter
      ablation of outflow tract ventricular ectopic beats.
AB  - BACKGROUND: Radiofrequency ablation (RFA) of outflow tract ventricular ectopic
      beats (OTVEBs) can be performed using a 4-mm or externally-cooled tip RFA
      catheter, but no data are available concerning the safety and efficacy of a large
      tip (8-mm) catheter. AIMS: To evaluate the feasibility of using an 8-mm tip
      catheter in patients with OTVEBs. METHODS: In this prospective cohort study, the
      8-mm tip catheter was tested in patients who were referred to our centre for RFA
      of symptomatic OTVEBs. RESULTS: The mean age of the 16 patients recruited between
      September 2008 and March 2010 was 53+/-18 years and 56.3% were male. Mean left
      ventricular ejection fraction was 62+/-9%, mean ventricular ectopic beat width
      was 144+/-21 ms, and all patients had left bundle branch block. Fourteen patients
      had inferior axis QRS morphology and two had superior. The main symptoms were
      palpitations and pre-syncope. RFA parameters were: procedure time 94+/-35 min;
      duration of application 11+/-10 min; impedance 81+/-12 Omega; temperature 50+/-5 
      degrees C; and power 46+/-17 W. RFA succeeded in 15 over 16 patients (93.8%); and
      recurrence was seen in one patient after a mean follow-up time of 11+/-6 months.
      No complications were noted. CONCLUSIONS: This preliminary study suggests that an
      8-mm tip catheter may represent an alternative for RFA in patients with OTVEBs in
      whom a 4-mm tip was not successful. Larger randomized studies are therefore
      warranted.

PMID- 22369916
TI  - Cardiovascular diseases and psychosocial factors at work.
AB  - Besides the 'classic' cardiovascular risk factors (high blood pressure,
      dyslipidaemia, metabolic syndrome and diabetes), the work environment is playing
      an increasingly significant role in cardiovascular morbidity and mortality.
      Several elements contribute to the effect of the work environment: physical
      factors, chemical factors, shift work and psychosocial factors. The effects of
      psychosocial factors on the aetiology and progression of cardiovascular disease
      have been confirmed by several studies. Identification of these work-related
      psychosocial factors must be taken into account when evaluating cardiovascular
      risk factors, in order to ensure better prevention.

PMID- 22369917
TI  - The role of natriuretic peptide testing in guiding chronic heart failure
      management: review of available data and recommendations for use.
AB  - The care of patients with heart failure can be challenging, with few objective
      tools available to assist in therapy decision-making. Natriuretic peptides are
      powerfully prognostic biomarkers in patients with heart failure and may represent
      an objective target for therapy. Accordingly, the use of biomarker-guided care
      with either B-type natriuretic peptide (BNP) or amino-terminal pro-B-type
      natriuretic peptide (NT-proBNP) has been recently explored. Over the past few
      years, a number of studies with heterogeneous inclusion criteria, methods and
      results have been performed. We have reviewed the available literature,
      summarizing the results of biomarker-guided heart failure trials and deriving
      recommendations for optimal application of biomarker-guided heart failure care
      based on the experience gained. In general, positive studies had low BNP or NT
      proBNP target concentrations (~100 pg/mL and ~1000 pg/mL, respectively) and
      achieved lower natriuretic peptide concentrations compared with standard care.
      Patients in the biomarker-guided arms of the studies typically received more
      aggressive heart failure care and had no excess adverse outcomes. In the recent
      ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study,
      patients treated with biomarker-guided care also had improved quality of life and
      significantly better reverse remodeling on echocardiography compared with
      patients who received standard care. In conclusion, heart failure therapy guided
      by a goal to reduce natriuretic peptide concentrations below prognostically
      meaningful levels results in more aggressive heart failure care, is well
      tolerated and is associated with superior outcomes.

PMID- 22369918
TI  - Localized dissection detected only by transoesophageal echocardiography.

PMID- 22369919
TI  - Percutaneous closure of a left superior vena cava draining directly into the left
      atrium in a child.

PMID- 22369920
TI  - Oscillatory synchronization model of attention to moving objects.
AB  - The world is a dynamic environment hence it is important for the visual system to
      be able to deploy attention on moving objects and attentively track them.
      Psychophysical experiments indicate that processes of both attentional
      enhancement and inhibition are spatially focused on the moving objects; however
      the mechanisms of these processes are unknown. The studies indicate that the
      attentional selection of target objects is sustained via a feedforward-feedback
      loop in the visual cortical hierarchy and only the target objects are represented
      in attention-related areas. We suggest that feedback from the attention-related
      areas to early visual areas modulates the activity of neurons; establishes
      synchronization with respect to a common oscillatory signal for target items via
      excitatory feedback, and also establishes de-synchronization for distractor items
      via inhibitory feedback. A two layer computational neural network model with
      integrate-and-fire neurons is proposed and simulated for simple attentive
      tracking tasks. Consistent with previous modeling studies, we show that via
      temporal tagging of neural activity, distractors can be attentively suppressed
      from propagating to higher levels. However, simulations also suggest attentional
      enhancement of activity for distractors in the first layer which represents
      neural substrate dedicated for low level feature processing. Inspired by this
      enhancement mechanism, we developed a feature based object tracking algorithm
      with surround processing. Surround processing improved tracking performance by
      57% in PETS 2001 dataset, via eliminating target features that are likely to
      suffer from faulty correspondence assignments.

PMID- 22369921
TI  - Nurse prescribing of medicines in Western European and Anglo-Saxon countries: a
      survey on forces, conditions and jurisdictional control.
AB  - BACKGROUND: The number of Western European and Anglo-Saxon countries where nurses
      are legally allowed to prescribe medicines is growing. As the prescribing of
      medicines has traditionally been the task of the medical profession, nurse
      prescribing is changing the relationship between the medical and nursing
      professions. OBJECTIVES: To gain more insight into the forces that led to the
      introduction of nurse prescribing of medicines in Western European and Anglo
      Saxon countries, as well as into the legal, educational and organizational
      conditions under which nurses prescribe in these countries. Moreover, this study
      sought to determine which consequences nurse prescribing has for the division of
      jurisdictional control over prescribing between the nursing and medical
      professions. DESIGN: International survey. PARTICIPANTS: An email survey was sent
      to 60 stakeholders of professional nursing or medical associations or government
      bodies, at national, state or provincial level across ten Western European and
      Anglo-Saxon countries, namely Australia, Canada, Finland, Ireland, the
      Netherlands, New Zealand, Spain, Sweden, the United Kingdom and the United States
      of America. METHODS: The survey addressed the reasons for the introduction of
      nurse prescribing and the conditions under which nurses are or will be
      prescribing medicines. RESULTS: The response rate was 65% (n=39). It was shown
      that a diversity of forces led to the introduction of nurse prescribing, and
      respondents from nursing and medical associations and government bodies cited
      different forces as being important for the introduction of nurse prescribing.
      Representatives of nurses' associations oftentimes emphasized the medication
      needs of patients living in remote geographical areas, while representatives of
      medical associations more often pointed to workforce shortages within the health
      care service. The conditions under which nurses prescribe medicines vary
      considerably, from countries where nurses prescribe independently to countries in
      which prescribing by nurses is only allowed under strict conditions and the
      supervision of physicians. CONCLUSIONS: Citing different forces as being
      important in the introduction of nurse prescribing can be conceived as a
      professional 'problem construction' in order to gain jurisdiction over the
      prescribing task. In most countries, nurses prescribe in a subordinate position
      and the jurisdiction over prescribing remains predominantly with the medical
      profession.

PMID- 22369922
TI  - Recent advances on the role of tumor exosomes in immunosuppression and disease
      progression.
AB  - Exosomes are endosomal-derived nanovesicles released by most cells types,
      including tumor cells, and principally involved in intercellular communication in
      physiology and disease. Tumor exosomes are gaining increasing interest in
      medicine and oncology as efficient tools for the delivery of defined signals.
      Representing the acellular replicas of tumor cells, they contain a great variety
      of bioactive molecules, such as proteins, RNA, miRNA and DNA. Their great ability
      to recirculate in body fluids and their structure allow them to transport their
      cargo to distant targets. Major studies have shown that tumor exosomes convey
      information not only between tumor cells but also to other cell types, including
      different immune cell components. There is increasing evidence that these
      nanovesicles may contribute to cancer progression by influencing different immune
      cell types, likely blunting specific T cell immunity and skewing innate immune
      cells toward a pro-tumorigenic phenotype. Because of this function and the
      additional property to deliver molecular signals modulating neoangiogenesis and
      stroma remodeling, tumor exosomes are believed to play a role in tumor
      progression by favoring metastatic niche onset. This review outlines the recent
      knowledge on immune suppressive mechanisms mediated by tumor exosomes. We will
      discuss our view on the role of these nanovesicular structures in cancer
      progression and how their presence could interfere with cancer therapy.

PMID- 22369923
TI  - Dependence of Cu, Pb and Zn remobilization on physicochemical properties of
      marine sediments.
AB  - The resuspension of 65 marine sediments was simulated in the laboratory with
      elutriates from 30 different sites from the north coast of Spain. The
      partitioning of Cu, Pb and Zn between sediment and elutriate was studied as a
      function of different physicochemical characteristics of the sediment: organic
      matter (OM), fine fraction (FF), redox potential and acid volatile sulfides
      (AVS). Mean remobilization factors (RF) -calculated as metal concentration in the
      elutriate (MUg/L) divided by metal concentration in the sediment (MUg/g dry
      weight)- were 0.072 for Cu, 0.012 for Pb and 0.071 for Zn. Remobilization of Pb
      was significantly lower than that of Cu and Zn. Although AVS, OM and FF presented
      a strong intercorrelation, OM explained great part of the variability on Cu and
      Pb remobilization while AVS did it for Zn. A multiple regression model
      considering both OM and AVS explained slightly better the remobilization of Pb
      and Cu, but not that of Zn.

PMID- 22369924
TI  - Cardiovascular and electrocortical markers of anger and motivation during a
      simulated driving task.
AB  - The experience of anger may have consequences for the long-term health of the
      individual. The psychophysiological manifestation of anger can vary in response
      to the motivational context of anger provocation. The current study was designed
      to investigate how motivational context (challenge vs. threat) influenced the
      cardiovascular system and frontal EEG asymmetry. 29 male participants completed a
      simulated driving journey with a fixed time schedule. Anger was induced by
      exposing participants to traffic delays at an early (challenge) and later point
      (threat) on the simulated route. A number of dependent variables were recorded,
      including 32 channels of EEG, measures of cardiovascular impedance, blood
      pressure and fEMG activity from the corrugator supercilii. The results indicated
      that traffic delays significantly increased blood pressure, heart rate, TPR and
      corrugator activity whilst reducing the relative level of left frontal activation
      in the EEG. However, there was little evidence for a consistent distinction
      between the early (challenge) and late (threat) introduction of traffic delay.
      The consequences of these findings for capturing the cardiovascular and
      electrocortical responses to anger induction are discussed.

PMID- 22369925
TI  - Diurnal variations in the outcomes of instrumented gait and quiet standing
      balance assessments and their association with falls history.
AB  - One in three adults aged over 65 falls every year, resulting in enormous costs to
      society. Incidents of falling vary with time of day, peaking in the early
      morning. The aim of this study was to determine if the ability of instrumented
      gait and balance assessments to discriminate between participants based on their
      falls history varies diurnally. Body-worn sensors were used during a 3 m gait
      assessment and a series of quiet standing balance tests. Each assessment was
      performed four times during a single day under supervised conditions in the
      participant's homes. 40 adults aged over 60 years (19 fallers) participated in
      this study. A range of parameters were derived for each assessment, and the
      ability of each parameter to discriminate between fallers and non-fallers at each
      recording time was examined. The effect of falls history on single support time
      varied significantly with recording time, with a significantly reduced single
      support time observed at the first and last recording session of the day.
      Differences were observed between fallers and non-fallers for a range of other
      gait parameters; however, these effects did not vary with assessment time. The
      quiet standing assessments examined in this study revealed significant variations
      with falls history; however, the sensitivity of the examined quiet standing
      assessments to falls risk does not appear to be time dependent. These results
      indicate that, with the exception of single support time, the association of gait
      and quiet standing balance parameters with falls risk does not vary diurnally.

PMID- 22369926
TI  - Views of emergency research (VERA): a qualitative study of women and their
      partners' views of recruitment to trials in severe postpartum haemorrhage.
AB  - OBJECTIVE: to explore women's and their partners' views of recruitment to
      emergency trials in severe postpartum haemorrhage (PPH). DESIGN: interview-based
      qualitative study. In semi-structured in-depth interviews, five recruitment
      options for a PPH trial in an emergency context were considered. SETTING:
      interviews were carried out in participants' homes. PARTICIPANTS: nine women who
      had experienced a severe PPH and six partners. FINDINGS: interviewees rejected
      three options; decision-making by women prior to delivery, and by partners and
      legal representatives at the time of the emergency. Preferred options were women
      making antenatal decisions about trial entry themselves, followed by doctors
      making decisions at the time of the emergency. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: recruitment options involving women and their partners at the time of
      an emergency were rejected. Antenatal decision-making raises logistical and
      ethical considerations for emergency trial teams. Further research is needed to
      address the possibility of antenatal decisions for emergency trials and to
      develop and assess supportive post-enrolment recruitment and information
      strategies which take into account the stressful context of clinical emergencies
      such as PPH.

PMID- 22369928
TI  - AZD4547: an orally bioavailable, potent, and selective inhibitor of the
      fibroblast growth factor receptor tyrosine kinase family.
AB  - The fibroblast growth factor (FGF) signaling axis is increasingly implicated in
      tumorigenesis and chemoresistance. Several small-molecule FGF receptor (FGFR)
      kinase inhibitors are currently in clinical development; however, the predominant
      activity of the most advanced of these agents is against the kinase insert domain
      receptor (KDR), which compromises the FGFR selectivity. Here, we report the
      pharmacologic profile of AZD4547, a novel and selective inhibitor of the FGFR1,
      2, and 3 tyrosine kinases. AZD4547 inhibited recombinant FGFR kinase activity in
      vitro and suppressed FGFR signaling and growth in tumor cell lines with
      deregulated FGFR expression. In a representative FGFR-driven human tumor
      xenograft model, oral administration of AZD4547 was well tolerated and resulted
      in potent dose-dependent antitumor activity, consistent with plasma exposure and
      pharmacodynamic modulation of tumor FGFR. Importantly, at efficacious doses, no
      evidence of anti-KDR-related effects were observed, confirming the in vivo FGFR
      selectivity of AZD4547. Taken together, our findings show that AZD4547 is a novel
      selective small-molecule inhibitor of FGFR with potent antitumor activity against
      FGFR-deregulated tumors in preclinical models. AZD4547 is under clinical
      investigation for the treatment of FGFR-dependent tumors.

PMID- 22369929
TI  - Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20
      to 44 years of age.
AB  - Depo-medroxyprogesterone acetate (DMPA) is an injectable contraceptive that
      contains the same progestin as the menopausal hormone therapy regimen found to
      increase breast cancer risk among postmenopausal women in the Women's Health
      Initiative clinical trial. However, few studies have evaluated the relationship
      between DMPA use and breast cancer risk. Here, we conducted a population-based
      case-control study among 1,028 women ages 20 to 44 years to assess the
      association between DMPA use and breast cancer risk. Detailed information on DMPA
      use and other relevant covariates was obtained through structured interviewer
      administered in-person questionnaires, and unconditional logistic regression was
      used to evaluate associations between various aspects of DMPA use and breast
      cancer risk. We found that recent DMPA use for 12 months or longer was associated
      with a 2.2-fold [95% confidence interval (CI), 1.2-4.2] increased risk of
      invasive breast cancer. This risk did not vary appreciably by tumor stage, size,
      hormone receptor expression, or histologic subtype. Although breast cancer is
      rare among young women and the elevated risk of breast cancer associated with
      DMPA appears to dissipate after discontinuation of use, our findings emphasize
      the importance of identifying the potential risks associated with specific forms
      of contraceptives given the number of available alternatives.

PMID- 22369930
TI  - What has proteomics taught us about Leishmania development?
AB  - Leishmania are obligatory intracellular parasitic protozoa that cycle between
      sand fly mid-gut and phagolysosomes of mammalian macrophages. They have developed
      genetically programmed changes in gene and protein expression that enable rapid
      optimization of cell function according to vector and host environments. During
      the last two decades, host-free systems that mimic intra-lysosomal environments
      have been devised in which promastigotes differentiate into amastigotes
      axenically. These cultures have facilitated detailed investigation of the
      molecular mechanisms underlying Leishmania development inside its host. Axenic
      promastigotes and amastigotes have been subjected to transcriptome and proteomic
      analyses. Development had appeared somewhat variable but was revealed by
      proteomics to be strictly coordinated and regulated. Here we summarize the
      current understanding of Leishmania promastigote to amastigote differentiation,
      highlighting the data generated by proteomics.

PMID- 22369931
TI  - [Comorbid states in paediatric and adolescent obesity. A simplified approach to
      their diagnosis: the metabolic syndrome].

PMID- 22369932
TI  - Glyphosate-induced stiffening of HaCaT keratinocytes, a Peak Force Tapping study
      on living cells.
AB  - The skin is the first physiological barrier, with a complex constitution, that
      provides defensive functions against multiple physical and chemical aggressions.
      Glyphosate is an extensively used herbicide that has been shown to increase the
      risk of cancer. Moreover there is increasing evidence suggesting that the
      mechanical phenotype plays an important role in malignant transformation. Atomic
      force microscopy (AFM) has emerged within the last decade as a powerful tool for
      providing a nanometer-scale resolution imaging of biological samples. Peak Force
      Tapping (PFT) is a newly released AFM-based investigation technique allowing
      extraction of chemical and mechanical properties from a wide range of samples at
      a relatively high speed and a high resolution. The present work uses the PFT
      technology to investigate HaCaT keratinocytes, a human epidermal cell line, and
      offers an original approach to study chemically-induced changes in the cellular
      mechanical properties under near-physiological conditions. These experiments
      indicate glyphosate induces cell membrane stiffening, and the appearance of
      cytoskeleton structures at a subcellular level, for low cytotoxic concentrations
      whereas cells exposed to IC50 (inhibitory concentration 50%) treatment exhibit
      control-like mechanical behavior despite obvious membrane damages. Quercetin, a
      well-known antioxidant, reverses the glyphosate-induced mechanical phenotype.

PMID- 22369933
TI  - The relation of serum gamma-glutamyl transferase levels with coronary lesion
      complexity and long-term outcome in patients with stable coronary artery disease.
AB  - BACKGROUND: Relation of serum gamma-glutamyl transferase (GGT) levels with
      extent, severity, and complexity of coronary artery disease has not been
      adequately studied. Therefore, we evaluated the relationship between GGT levels
      and coronary complexity, severity and extent assessed by SYNTAX score and long
      term adverse events. METHODS: We enrolled 442 consecutive patients with stable
      angina pectoris who underwent coronary angiography. Baseline serum GGT levels
      were measured and SYNTAX score was calculated from the study population. Median
      follow-up duration was 363 days. Endpoints were all cause mortality and any
      revascularization. RESULTS: GGT levels demonstrated an increase from low SYNTAX
      tertile to high tertile. In multivariate analysis serum GGT, diabetes mellitus,
      HDL-cholesterol, eGFR and ejection fraction were found to be independent
      predictors of high SYNTAX score. The survival analysis showed that long-term
      revascularization rates were comparable between the GGT groups (for 36 U/l cut
      point) of the overall population (7.7% vs 8.6% logrank, p = 0.577), whereas long
      term all cause mortality rate was higher in the GGT >= 36 U/l group (3.6% vs
      11.6% logrank, p = 0.001). In Cox proportional hazards regression model, GGT >=
      36 U/l group was found to be an independent predictor of long-term all cause
      mortality in the unadjusted (HR 2.54, 95% CI 1.17-5.48, p = 0.018) and age- and
      gender-adjusted (HR 2.58, 95% CI 1.19-5.58, p = 0.016) models. CONCLUSION: Serum
      GGT level was independently associated with coronary complexity and long-term
      mortality in patients with stable coronary artery disease.

PMID- 22369934
TI  - Circulating high-mobility group box 1 and cardiovascular mortality in unstable
      angina and non-ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: High-mobility group box 1 (HMGB1) is a damage-associated molecular
      pattern molecule, which suggests a potential role of this protein in the
      pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been
      shown to be independently associated with cardiac mortality in ST-segment
      elevation myocardial infarction. However, its prognostic value remains unclear in
      unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI).
      METHODS: HMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I
      and B-type natriuretic peptide concentrations were measured on admission in 258
      consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24h
      (mean, 7.4h) of the onset of chest symptoms. RESULTS: A total of 38 (14.7%)
      cardiovascular deaths, including 10 in-hospital deaths, occurred during a median
      follow-up period of 49 months after admission. In a stepwise Cox regression
      analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk
      (RR) 3.24 per 10-fold increment; P = 0.0003], cardiac troponin I (RR 1.83 per 10
      fold increment, P = 0.0007), Killip class>1 (RR 4.67, P = 0.0001) and age (RR
      1.05 per 1-year increment, P = 0.03), but not hsCRP, were independently
      associated with cardiovascular mortality. In-hospital and cardiovascular
      mortality rates were higher in patients with increased HMGB1 (>= 2.4 ng/mL of
      median value) than those without increased HMGB1 (6.3% vs. 1.5%, P = 0.04; and
      23% vs. 6.9%, P = 0.0003). CONCLUSION: Circulating concentration of HMGB1 on
      admission may be a potential and independent predictor of cardiovascular
      mortality in patients hospitalized for UA/NSTEMI within 24h of onset.

PMID- 22369935
TI  - In search of a marker of vulnerable carotid plaque: is the key in the heart?

PMID- 22369936
TI  - The glycan-binding properties of the cation-independent mannose 6-phosphate
      receptor are evolutionary conserved in vertebrates.
AB  - The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays an
      essential role in the biogenesis of lysosomes by delivering newly synthesized
      lysosomal enzymes from the trans Golgi network to the endosomal system. The CI
      MPR is expressed in most eukaryotes, with Saccharomyces cerevisiae and
      Caenorhabditis elegans being notable exceptions. Although the repertoire of
      glycans recognized by the bovine receptor has been studied extensively, little is
      known concerning the ligand-binding properties of the CI-MPR from non-mammalian
      species. To assess the evolutionary conservation of the CI-MPR, surface plasmon
      resonance analyses using lysosomal enzymes with defined N-glycans were carried
      out to probe the glycan-binding specificity of the Danio rerio CI-MPR. The
      results demonstrate that the D. rerio CI-MPR harbors three glycan-binding sites
      that, like the bovine CI-MPR, map to domains 3, 5 and 9 of its 15-domain
      containing extracytoplasmic region. Analyses on a phosphorylated glycan
      microarray further demonstrated the unique binding properties of each of the
      three sites and showed that, similar to the bovine CI-MPR, only domain 5 of the
      D. rerio CI-MPR is capable of recognizing Man-P-GlcNAc-containing glycans.

PMID- 22369937
TI  - Differential response of salt stress on Brassica juncea: photosynthetic
      performance, pigment, proline, D1 and antioxidant enzymes.
AB  - To investigate the ability of sensitive and tolerant variety of Brassica juncea
      to adapt to a saline environment in a field, we examined the activities of
      antioxidant enzymes in relation to photosystem II, chlorophyll a fluorescence,
      photosynthetic pigment concentration, protein (D1) and proline in plants exposed
      to salt stress. We observed a greater decline in the photosynthetic rate (?F/Fm')
      and electron transport rate (ETRsat) and saturating photosynthetically active
      photo flux density (PPFDsat) under salt stress in var. Urvashi (sensitive
      variety) than in var. Bio902 (tolerant variety). Var. Urvashi was found to be
      more sensitive to high salinity. In var. Bio902, chlorophyll a, chlorophyll b and
      total chlorophyll concentrations were higher than in the sensitive variety.
      Proline and protein contents were also higher in var. Bio902 as compared to their
      lower accumulation in var. Urvashi. The improved performance of the var. Bio902
      under high salinity was accompanied by an increase in ascorbate peroxidase (APX,
      EC 1.11.1.11) and catalase (CAT, EC 1.11.1.6), though no salt-dependent increase
      in the activity of superoxide dismutase (SOD, EC 1.15.1.1) was observed. However,
      no such increase in APX and CAT was observed in var. Urvashi, though there was
      significant increase in SOD activity. These results suggest that var. Bio902 is
      potentially more tolerant to salt damage and is associated with better adaptive
      responses found in var. Bio902 than var. Urvashi. Increased photoinhibition in
      var. Urvashi as observed by its reduced thylakoid membrane protein, D1 probably
      results from the greater photosynthetic damage caused by salt stress than var.
      Bio902.

PMID- 22369938
TI  - Biochemical characterization of a recombinant Swainsona canescens calcium
      dependent protein kinase (ScCPK1).
AB  - Calcium-dependent protein kinases (CPKs) constitute a unique family of kinases
      involved in many physiological responses in plants. Biochemical and kinetic
      properties of a recombinant Swainsona canescens calcium-dependent protein kinase
      (ScCPK1) were examined in this study. The optimum pH and temperature for activity
      were pH 7.5 and 37  degrees C, respectively. Substrate phosphorylation activity
      of ScCPK1 was calmodulin (CaM) independent. Yet CaM antagonists, W7 [N-(6
      aminohexyl)-5-chloro-1-naphthalene sulphonamide] and calmidazolium inhibited the
      activity with IC(50) values of 750 nM and 350 MUM, respectively. Both serine and
      threonine residues were found to be phosphorylated in autophosphorylated ScCPK1
      and in histone III-S phosphorylated by ScCPK1. The [Ca(2)(+)] for half maximal
      activity (K(0.5)) was found to be 0.4 MUM for ScCPK1 with histone III-S as
      substrate. Kinetic analysis showed that K(M) of ScCPK1 for histone III-S was 4.8
      MUM. These data suggest that ScCPK1 is a functional Ser/Thr kinase, regulated by
      calcium, and may have a role in Ca(2)(+)-mediated signaling in S. canescens.

PMID- 22369939
TI  - Evaluation of solitary pulmonary nodule in human immunodeficiency virus infected
      patients.
AB  - BACKGROUND: While the etiologies of solitary pulmonary nodules (SPNs) in
      immunocompetent patients are well established, common etiology, diagnostic
      techniques, and guidelines to assess SPNs in patients infected with human
      immunodeficiency virus (HIV) have not been established. OBJECTIVE: To define the
      etiology of SPN in HIV-infected patients and to examine efficacy of diagnostic
      testing for SPN. METHODS: We performed a retrospective chart review of HIV
      infected patients admitted to a designated acquired immune deficiency syndrome
      (AIDS) center. Microbiological and histopathological  specimens from sputum,
      bronchoalveolar lavage, and biopsies were analyzed. Charts were fully analyzed
      from time of admission until definitive diagnosis or loss to follow-up. RESULTS:
      During the 10-year observational period, 10 of 5,000 HIV-infected patients
      admitted to the hospital were diagnosed  with SPN via chest radiography or
      computed tomography (CT). Among these 10 patients, 6 had a definitive diagnosis.
      Underlying etiologies included infection (5/10) and lung adenocarcinoma (1/10);
      none were identified in the remaining 4 subjects. Sputum analysis provided no
      diagnostic value  in discovering pathogenesis in any of these cases. Fiberoptic
      bronchoscopy with bronchoalveolar lavage and transbronchial biopsy were
      diagnostic in 3 cases, while CT-guided percutaneous transthoracic needle biopsy
      (PTNB) was diagnostic in 2 cases. One patient required open lung biopsy.
      CONCLUSIONS: Etiologies of SPN in HIV-infected patients are varied and difficult
      to diagnose. In our study, SPN was attributable to infectious etiology in 50% of
      cases. Sputum analysis was of no diagnostic value. Biopsy is necessary for
      definitive diagnosis and treatment.

PMID- 22369940
TI  - Amino acid residues of both the extracellular and transmembrane domains influence
      binding of the antiparasitic agent milbemycin to Haemonchus contortus AVR-14B
      glutamate-gated chloride channels.
AB  - Glutamate-gated chloride (GluCl) channels are pentameric receptors for the
      inhibitory neurotransmitter glutamate in invertebrates and are a major target for
      macrolide anthelmintics. Three amino acids in GluCl channels are reported to
      render macrolide resistance in nematodes and insects. To examine whether these
      three amino acids are involved in binding of the antiparasitic agent milbemycin
      (MLM) to the GluCl channels of the nematode parasite Haemonchus contortus, the
      equivalent amino acids (L256, P316, and G329) of the Hco-AVR-14B subunit were
      substituted with various amino acids. cDNAs encoding the wild type and mutants of
      this subunit were transfected into COS-1 cells for transient expression and
      analysis of GluCl channels. The abilities of these mutant channels to bind
      [(3)H]MLM A(4) were remarkably decreased when compared with the wild-type
      channel. In patch clamp analysis, L256F and P316S mutant channels were 37- and
      100-fold less sensitive to MLM A(4) when compared with the wild-type channel,
      respectively. These findings indicate that amino acid changes in the beta10
      strand, the M2-M3 linker, and the M3 region influence MLM A(4) binding to the
      channel. Homology modeling and ligand docking studies suggest the presence of two
      potential binding sites for MLM A(4).

PMID- 22369941
TI  - Interaction of Berberine derivative with protein POT1 affect telomere function in
      cancer cells.
AB  - The protein POT1 plays an important role in telomere protection, which is related
      with telomere elongation and cell immortality. The protein has been recognized as
      a promising drug target for cancer treatment. In the present study, we cloned,
      overexpressed in Escherichia coli for the first time, and purified recombinant
      human POT1. The protein was proved to be active through filter binding assay,
      FRET and CD experiments. In the initial screening for protein binding ligands
      using SPR, compound Sysu-00692 was found to bind well with the POT1, which was
      confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692
      could interfere with the binding between human POT1 and the telomeric DNA through
      chromatin immunoprecipitation. Besides, the compound showed mild inhibition on
      telomerase and cell proliferation. As we know, compound Sysu-00692 is the first
      reported POT1-binding ligand, which could serve as a lead compound for further
      improvement. This work offered a potentially new approach for drug design for the
      treatment of cancers.

PMID- 22369942
TI  - An impairment of cortical GABAergic neurons is involved in alkalosis-induced
      brain dysfunctions.
AB  - Acid-base imbalance leads to pathological cognition and behaviors in the clinical
      practices. In the comparison with acidosis, the cellular mechanisms underlying
      alkalosis-induced brain dysfunction remain unclear. By using electrophysiological
      approach, we investigated the influences of high extracellular pH environment on
      cortical GABAergic neurons in terms of their responsiveness to synaptic inputs
      and their ability to produce action potentials. Artificial cerebral spinal fluid
      in high pH impairs excitatory synaptic transmission and spike initiation in
      cortical GABAergic neurons. The alkalosis-induced dysfunction of GABAergic
      neurons is associated with the decrease of receptor responsiveness and the
      increases of spike refractory periods and threshold potentials. Our studies
      reveal that alkalosis impairs cortical GABAergic neurons and subsequently
      deteriorate brain functions. The molecular targets for alkalosis action include
      glutamate receptor-channels and voltage-gated sodium channels on GABAergic
      neurons.

PMID- 22369944
TI  - Phosphorylation prevents C/EBPbeta from the calpain-dependent degradation.
AB  - CCAAT/enhancer-binding protein (C/EBP) beta plays an important role in
      proliferation and differentiation of 3T3-L1 preadipocytes. C/EBPbeta is
      sequentially phosphorylated during the 3T3-L1 adipocyte differentiation program,
      first by MAPK/Cyclin A/cdk2 on Thr(188) and subsequently by GSK3beta on Ser(184)
      or Thr(179). Dual phosphorylation is critical for the gain of DNA binding
      activity of C/EBPbeta. In this manuscript, we found that phosphorylation also
      contributed to the stability of C/EBPbeta. Both ex vivo and in vitro experiments
      showed that phosphorylation by MAPK/Cyclin A/cdk2 and GSK3beta protected
      C/EBPbeta from MU-calpain-mediated proteolysis, while phosphorylation on Thr(188)
      by MAPK/Cyclin A/cdk2 contributed more to the stabilization of C/EBPbeta, Further
      studies indicated that phosphorylation mimic C/EBPbeta was insensitive to both
      calpain accelerator and calpain inhibitor. Thus, phosphorylation might contribute
      to the stability as well as the gain of DNA binding activity of C/EBPbeta.

PMID- 22369943
TI  - Characterization of cancer stem cell properties of CD24 and CD26-positive human
      malignant mesothelioma cells.
AB  - Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by
      rapid growth and poor prognosis. In our previous study, we have demonstrated that
      several cancer stem cell (CSC) markers correlated with CSC properties in MM
      cells. Among these markers, we focused on two: CD24, the common CSC marker, and
      CD26, the additional CSC marker. We further analyzed the CSC properties of CD24
      and CD26-positve MM cells. We established RNAi-knockdown cells and found that
      these markers were significantly correlated with chemoresistance, proliferation,
      and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed
      both CD24 and CD26, the presence of each of these two markers was correlated with
      different CSC property. In addition, downstream signaling of these markers was
      explored by microarray analysis, which revealed that their expressions were
      correlated with several cancer-related genes. Furthermore, phosphorylation of ERK
      by EGF stimulation was significantly affected by the expression of CD26, but not
      CD24. These results suggest that CD24 and CD26 differentially regulate the CSC
      potentials of MM and could be promising targets for CSC-oriented therapy.

PMID- 22369945
TI  - Phosphorylation of beta-catenin at serine 663 regulates its transcriptional
      activity.
AB  - beta-Catenin, a component of Wnt signaling, plays a key role in colorectal
      carcinogenesis. The phosphorylation status of beta-catenin determines its fate
      and affects its cellular function, and serine 675 (S675) was previously
      identified as a common target of p21-activated kinase 1 (PAK1) and protein kinase
      A. In the present study, we explored the PAK1-specific phosphorylation site(s) in
      beta-catenin. Active PAK1 T423E but not inactive PAK1 K299R interacted with and
      phosphorylated beta-catenin. Mutagenesis followed by a kinase assay revealed that
      PAK1 phosphorylated S663 in addition to S675, and an anti-phospho-beta
      catenin(S663) antibody detected the phosphorylation of S663 downstream of PAK1 in
      various human colon cancer cells. Furthermore, the Wnt3a-stimulated S663
      phosphorylation was inhibited by the PAK1-specific inhibitor, IPA-3, but not by H
      89 or LY294002. The non-phosphorylatable mutant forms of beta-catenin, S663A,
      S675A and S663/675A, showed similar defects in their PAK1-induced TCF/LEF
      transactivation, whereas the phosphomimetic form of beta-catenin, S663D,
      demonstrated a transcriptional activity that was comparable to that of beta
      catenin S675D and beta-catenin S663D/S675D. Taken together, these results provide
      evidence that PAK1 specifically phosphorylates beta-catenin at S663 and that this
      phosphorylation is essential for the PAK1-mediated transcriptional activation of
      beta-catenin.

PMID- 22369946
TI  - Identification of miR-508-3p and miR-509-3p that are associated with cell
      invasion and migration and involved in the apoptosis of renal cell carcinoma.
AB  - MicroRNAs (miRNAs) have emerged as powerful regulators of multiple processes
      linked to human cancer, including cell apoptosis, proliferation and migration,
      suggesting that the regulation of miRNA function could play a critical role in
      cancer progression. Recent studies have found that human serum/plasma contains
      stably expressed miRNAs. If they prove indicative of disease states, miRNAs
      measured from peripheral blood samples may be a source for routine clinical
      detection of cancer. Our studies showed that both miR-508-3p and miR-509-3p were
      down-regulated in renal cancer tissues. The level of miR-508-3p but not miR-509
      3p in renal cell carcinoma (RCC) patient plasma demonstrated significant
      differences from that in control plasma. In addition, the overexpression of miR
      508-3p and miR-509-3p suppressed the proliferation of RCC cells (786-0), induced
      cell apoptosis and inhibited cell migration in vitro. Our data demonstrated that
      miR-508-3p and miR-509-3p played an important role as tumor suppressor genes
      during tumor formation and that they may serve as novel diagnostic markers for
      RCC.

PMID- 22369947
TI  - Identification of novel kynurenine production-inhibiting benzenesulfonamide
      derivatives in cancer cells.
AB  - Kynurenine (Kyn), a metabolite of tryptophan (Trp), is known to be a key
      regulator of human immune responses including cancer immune tolerance. Therefore,
      abrogation of Kyn production from cancer cells by small molecules may be a
      promising approach to anticancer therapy. Indeed, several small molecule
      inhibitors of indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in the
      catabolism of Trp to Kyn, exert antitumor effects in animal models. We screened
      our chemical libraries using a cell-based Kyn production assay to identify a new
      type of small molecules that regulate Kyn production, and for the first time
      identified a benzenesulfonamide derivative (compound 1) as a hit with the ability
      to inhibit Kyn production in interferon-gamma (IFN-gamma)-stimulated A431 and
      HeLa cells. Unlike the previously identified S-benzylisothiourea derivative,
      compound 2, compound 1 had little effect on the enzymatic activity of recombinant
      human IDO in vitro but suppressed the expression of IDO at the mRNA level in
      cells. Furthermore, compound 1 suppressed STAT1-dependent transcriptional
      activity and DNA binding, whereas no decrement in either the expression or
      phosphorylation level of STAT1 was observed. The inhibition of IDO expression by
      several benzenesulfonamide derivatives is associated with the suppression of
      STAT1. Thus, compound 1 and its analogs might be useful for analyzing the
      regulation of IDO activation, and STAT1-targeting could be an alternative to the
      IDO-directed approach for the regulation of Kyn levels by small molecules in the
      tumor microenvironment.

PMID- 22369948
TI  - Up-regulation of matrix metalloproteinase-1 and interleukin-6 expression in
      cocultures of corneal fibroblasts and neural cells.
AB  - The cornea is the most sensitive tissue in the human body, with the dense nerve
      endings of the cornea being derived from the first division of the ophthalmic
      nerve. The existence of such organized nerve fibers reflects the role of neural
      regulation in corneal homeostasis, with the proper distribution and function of
      these nerve fibers thus being required for maintenance of a healthy cornea. We
      recently established an in vitro model, based on the coculture of human corneal
      epithelial cells and fibroblasts on opposite sides of a collagen vitrigel
      membrane. We have now examined the role of neural cells in corneal homeostasis
      with the use of a similar coculture system. Reverse transcription-polymerase
      chain reaction and immunoblot analyses showed that the presence of neural cells
      (differentiated PC12 cells) increased the expression of matrix metalloproteinase
      1 (MMP-1) in human corneal fibroblasts at both the mRNA and protein levels. The
      expression of MMP-2 and MMP-9 in corneal fibroblasts was not affected by PC12
      cells. Furthermore, a multiplex assay showed that, among various cytokines
      assayed, only the release of interleukin-6 in cocultures of the two cell types
      was markedly greater than that in cultures of corneal fibroblasts alone. These
      results thus suggest that factors released from neural cells may play an
      important role in regulation of the function of corneal fibroblasts and thereby
      contribute to the maintenance of corneal structure and function.

PMID- 22369949
TI  - Functional characterization of lipase in the pathogenesis of Staphylococcus
      aureus.
AB  - During infection, Staphylococcus aureus produces multiple enzymes that enable it
      to invade and destroy host tissues and metastasize to other sites. One such
      enzyme, lipase, has been recognized for its relationship in the virulence of S.
      aureus. However, a direct involvement of lipase in the pathogenesis of S. aureus
      remains to be demonstrated. Our prior study indicated that anti-lipase serum
      inhibits biofilm formation in S. aureus clinical strains. The aim of this study
      was to further characterize the roles of lipase in the pathogenesis in S. aureus.
      We found that deletion of the lipase-coding gene reduced biofilm formation
      relative to the wild-type strain. This was shown by culture in 96-well plates
      coated with collagen to resemble the in vivo infection process. Intraperitoneal
      inoculation of mice with a lipase mutant strain showed defective formation of
      peritoneal abscesses, and bacterial loads in different organs were much lower
      compared with the wild-type. Importantly, active immunization with recombinant
      lipase protected mice against a lethal challenge with S. aureus. Altogether, our
      data provide evidence that S. aureus lipase plays important roles in the
      pathogenesis of S. aureus.

PMID- 22369950
TI  - Patients and staff perceptions of cancer patients' quality of life.
AB  - BACKGROUND: Discrepancies exist in estimation of quality of life (QL) by patients
      and caregivers but underlying factors are incompletely characterised. METHODS: QL
      of 153 patients was estimated by themselves, by 70 nurses and by 53 physicians in
      a cross-sectional study. Variables which could influence inter-rater agreement
      were evaluated. RESULTS: Inter-rater agreement of QL was fair (r = .292) between
      patients and nurses and between patients and physicians (r = .154). Inter-rater
      agreement with nurses was significantly lower concerning fatigue and pain for
      patients with a Karnofsky Index <50 when compared to patients with a KI > 50.
      Their inter-rater agreement with physicians was significantly lower for fatigue,
      pain and physical functioning. Agreement on the degree of anxiety was
      significantly (p = .009) better for female patients. Agreement on the need for
      social assistance (p = .01) and physical functioning (p = .03) was significantly
      better for male patients. Agreement with patients on their physical functioning
      was significantly (p = .03) better for male nurses and male physicians (r = .944)
      than for female nurses and female physicians (r = .674). CONCLUSIONS: Our study
      showed that estimation of overall QL of patients by professional caregivers is
      inaccurate. Inter-rater agreement was influenced by KI of patients, by gender of
      patients and caregivers and by professional experience of nurses.

PMID- 22369951
TI  - Clustering of unhealthy behaviors in a Brazilian population of industrial
      workers.
AB  - OBJECTIVE: To analyze the clustering of four unhealthy behaviors (tobacco use,
      excessive alcohol consumption, physical inactivity and low consumption of fruits
      and vegetables) and their association with sociodemographic factors among adult
      industrial workers in Brazil. METHODS: Data from 23 Brazilian states and the
      Federal District were collected via questionnaire from 2006 to 2008. Clustering
      of risk behaviors was identified using the ratio between the observed and
      expected percentages of each combination of unhealthy behaviors. RESULTS: Among
      the 44,477 workers surveyed, 18.0% of men and 11.4% of women accumulated three or
      four unhealthy behaviors. The most frequent combination was physical inactivity
      and low consumption of fruits and vegetables. The concurrent presence of all four
      behaviors was 86% higher in men and 148% higher in women than would be predicted
      if the frequency of these behaviors were independent. Presence of one or more
      negative behaviors was more frequent in men, younger individuals and in those
      with lower levels of education and family income than subjects without these
      characteristics. CONCLUSIONS: There was a strong tendency for unhealthy behaviors
      to assume combinatorial patterns, mainly in men, people with less education,
      income, and age, suggesting important disparities.

PMID- 22369952
TI  - Evidence of interactions in Co-HfO2 granular films.
AB  - Co-HfO(2) granular films with varying numbers of bilayers were studied by means
      of transmission electron microscopy (TEM), magnetization loops and zero-field
      cooled and field-cooled (ZFC-FC) magnetization. Grain size properties inferred
      from the measurement techniques were found to be different from those observed
      from TEM. We show that a modified Langevin function that accounts for dipolar
      interactions reconciles grain size properties observed by TEM. The mean blocking
      temperature seen from ZFC-FC analysis was observed to be greater compared to that
      inferred from TEM data. Moreover, it exhibited a trend with increasing numbers of
      bilayers. We proposed an explanation for these differences on the basis of the
      degree of dipolar interactions.

PMID- 22369953
TI  - In vivo quantification of bone-fluorine by delayed neutron activation analysis: a
      pilot study of hand-bone-fluorine levels in a Canadian population.
AB  - Humans can be exposed to fluorine (F) through their diet, occupation, environment
      and oral dental care products. Fluorine, at proper dosages, is believed to have
      positive effects by reducing the incidence of dental caries, but fluorine
      toxicity can occur when people are exposed to excessive quantities of fluorine.
      In this paper we present the results of a small pilot in vivo study on 33
      participants living in Southwestern Ontario, Canada. The mean age of participants
      was 45 +/- 18 years with a range of 20-87 years. The observed calcium normalized
      hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to
      8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone
      above the detection limit of the system. The average fluorine concentration in
      bone was found to be 3.5 +/- 0.4 mg F/g Ca. No difference was observed in average
      concentration for men and women. In addition, a significant correlation (r(2) =
      0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The
      amount of fluorine was found to increase at a rate of 0.084 +/- 0.014 mg F/g Ca
      per year. There was no significant difference observed in this small group of
      subjects between the accumulation rates in men and women. To the best of our
      knowledge, this is the first time data from in vivo measurement of fluorine
      content in humans by neutron activation analysis have been presented. The data
      determined by this technique were found to be consistent with results from ex
      vivo studies from other countries. We suggest that the data demonstrate that this
      low risk non-invasive diagnostic technique will permit the routine assessment of
      bone-fluorine content with potential application in the study of clinical bone
      related diseases. This small study demonstrated that people in Southern Ontario
      are exposed to fluoride in measureable quantities, and that fluoride can be seen
      to accumulate in bone with age. However, all volunteers were found to have levels
      below those expected with clinical fluorosis, and only one older subject was
      found to have levels comparable with preclinical exposure.

PMID- 22369954
TI  - More than preparing a meal? Concerning the meanings of home cooking.
AB  - Cooking is one of the basic activities in our lives. However, people frequently
      feel they fall short of time to cook when facing problems with the temporal
      organization of daily life. How people think about home cooking is considered to
      be important for the time they spend on preparing meals. It is assumed that the
      meaning of cooking differs for different people, depending on the temporal and
      social context. This contribution allows us to clarify how the meaning of cooking
      varies according to individual and household characteristics and the cooking
      occasion. By using the pooled time-diary data from the Flemish time-use surveys
      from 1999 and 2004 we can examine people's views on cooking in order to
      understand how people use time for food preparation. Although the results suggest
      that people consider cooking primarily as a household chore, preparing food can
      also be a way to please others, as well as themselves. It seems that feelings of
      time pressure and the family situation are clearly related to men's and women's
      cooking experiences. Furthermore, the meaning of cooking also tends to be clearly
      influenced by the meal situation and (the moment of) the day.

PMID- 22369955
TI  - Qualitative research using photo-elicitation to explore the role of food in
      family relationships among obese adolescents.
AB  - Obesity in adolescence is a major public health issue. Family relationships have
      an important role, whether in the onset of the condition, its maintenance, or the
      way in which the problem is approached. Food and family relationships are two
      major elements in therapeutic care. The subject of the present study is the
      investigation of the place of food within family relationships among obese
      adolescents, so as to tailor care strategies. Twelve semi-structured interviews
      were conducted among adolescents presenting obesity and their parents. The
      investigation was qualitative, and used photo-elicitation. A photograph produced
      by the subject is used as the basis for narrative, and the verbal material
      obtained is analysed using Interpretative Phenomenological Analysis. The results
      can be categorised along two axes. The first describes the place of food in the
      one-to-one parent-child relationship; the second describes the organisation of
      the family group. This study evidenced two possible lines of approach in
      understanding the place of food in these families. There are major interrelations
      between food and relationships within the family, so that implications for
      therapy can be drawn: taking account of bonding between parent and child, and
      therapeutic orientation towards family functioning rather than towards individual
      eating patterns.

PMID- 22369956
TI  - Consistency of metabolic responses and appetite sensations under postabsorptive
      and postprandial conditions.
AB  - The present study aimed to investigate the reliability of metabolic and
      subjective appetite responses under fasted conditions and following consumption
      of a cereal-based breakfast. Twelve healthy, physically active males completed
      two postabsorption (PA) and two postprandial (PP) trials in a randomised order.
      In PP trials a cereal based breakfast providing 1859 kJ of energy was consumed.
      Expired gas samples were used to estimate energy expenditure and fat oxidation
      and 100mm visual analogue scales were used to determine appetite sensations at
      baseline and every 30 min for 120 min. Reliability was assessed using limits of
      agreement, coefficient of variation (CV), intraclass coefficient of correlation
      and 95% confidence limits of typical error. The limits of agreement and typical
      error were 292.0 and 105.5 kJ for total energy expenditure, 9.3 and 3.4 g for
      total fat oxidation and 22.9 and 8.3mm for time-averaged AUC for hunger
      sensations, respectively over the 120 min period in the PP trial. The reliability
      of energy expenditure and appetite in the 2h response to a cereal-based breakfast
      would suggest that an intervention requires a 211 kJ and 16.6mm difference in
      total postprandial energy expenditure and time-averaged hunger AUC to be
      meaningful, fat oxidation would require a 6.7 g difference which may not be
      sensitive to most meal manipulations.

PMID- 22369957
TI  - Physiological responses of food neophobics and food neophilics to food and non
      food stimuli.
AB  - Individual differences in human food neophobia (the reluctance to try novel
      foods) and food neophilia (the overt willingness to try novel foods) influence
      the evaluation of tastes and odors, as well as the sampling of such stimuli. Past
      research also notes an association of food neophobia to PTC sensitivity, body
      weight, and cephalic phase salivary response. The present study assessed
      physiological reactions of food neophobics and neophilics to pictures of food and
      non-food stimuli. Stimuli pictures were presented in random order on a computer
      screen for a period of 5 min. No significant differences were found between the
      groups in relation to non-food stimuli. However, pulse, GSR, and respirations
      were significantly increased in food neophobics when presented pictures of food
      stimuli. Thus, further evidence is provided to support a physiological component
      at least partially responsible for differences noted between neophobics and
      neophilics in sensitivity, psychophysical ratings, and "willingness to try"
      personality. Such a component may also lead to differences in weight, nutrition,
      and overall health.

PMID- 22369958
TI  - Use of a clay modeling task to reduce chocolate craving.
AB  - Elaborated Intrusion theory (EI theory; Kavanagh, Andrade, & May, 2005) posits
      two main cognitive components in craving: associative processes that lead to
      intrusive thoughts about the craved substance or activity, and elaborative
      processes supporting mental imagery of the substance or activity. We used a novel
      visuospatial task to test the hypothesis that visual imagery plays a key role in
      craving. Experiment 1 showed that spending 10 min constructing shapes from
      modeling clay (plasticine) reduced participants' craving for chocolate compared
      with spending 10 min 'letting your mind wander'. Increasing the load on verbal
      working memory using a mental arithmetic task (counting backwards by threes) did
      not reduce craving further. Experiment 2 compared effects on craving of a simpler
      verbal task (counting by ones) and clay modeling. Clay modeling reduced overall
      craving strength and strength of craving imagery, and reduced the frequency of
      thoughts about chocolate. The results are consistent with EI theory, showing that
      craving is reduced by loading the visuospatial sketchpad of working memory but
      not by loading the phonological loop. Clay modeling might be a useful self-help
      tool to help manage craving for chocolate, snacks and other foods.

PMID- 22369959
TI  - Emotional eating and its effect on eating behaviour after a natural disaster.
AB  - Emotional eaters are hypothesised to overeat in response to negative emotions or
      stress. However, the empirical evidence for such a moderating role is mixed. This
      study examined the effect of emotional eating on eating behaviour before and
      after the occurrence of a natural disaster (an earthquake) in a sample of
      predominantly middle-aged and older women. As expected, women who scored high on
      emotional eating reported an increase in overeating after the earthquake. This
      effect was qualified by an interaction: emotional eaters who reported high levels
      of post-earthquake distress reported an increase in overeating, whereas non
      stressed emotional eaters and non-emotional eaters did not.

PMID- 22369960
TI  - Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig
      model.
AB  - Lacking a blood supply and having a low cellular density, articular cartilage has
      a minimal ability for self-repair. Therefore, wide-ranging cartilage damage
      rarely resolves spontaneously. Cartilage damage is typically treated by
      chondrocyte transplantation, mosaicplasty or microfracture. Recent advances in
      tissue engineering have prompted research on techniques to repair articular
      cartilage damage using a variety of transplanted cells. We studied the repair and
      regeneration of cartilage damage using layered chondrocyte sheets prepared on a
      temperature-responsive culture dish. We previously reported achieving robust
      tissue repair when covering only the surface layer with layered chondrocyte
      sheets when researching partial-thickness defects in the articular cartilage of
      domestic rabbits. The present study was an experiment on the repair and
      regeneration of articular cartilage in a minipig model of full-thickness defects.
      Good safranin-O staining and integration with surrounding tissues was achieved in
      animals transplanted with layered chondrocyte sheets. However, tissue having poor
      safranin-O staining-not noted in the domestic rabbit experiments-was identified
      in some of the animals, and the subchondral bone was poorly repaired in these.
      Thus, although layered chondrocyte sheets facilitate articular cartilage repair,
      further investigations into appropriate animal models and culture and transplant
      conditions are required.

PMID- 22369961
TI  - The in vitro preconditioning of myoblasts to enhance subsequent survival in an in
      vivo tissue engineering chamber model.
AB  - The effects of in vitro preconditioning protocols on the ultimate survival of
      myoblasts implanted in an in vivo tissue engineering chamber were examined. In
      vitro testing: L6 myoblasts were preconditioned by heat (42  degrees C; 1.5 h);
      hypoxia (<8% O(2); 1.5 h); or nitric oxide donors: S-nitroso-N
      acetylpenicillamine (SNAP, 200 MUM, 1.5 h) or 1-[N-(2-aminoethyl)-N-(2
      aminoethyl)amino]-diazen-1-ium-1,2-diolate (DETA-NONOate, 500 MUM, 7 h).
      Following a rest phase preconditioned cells were exposed to 24 h hypoxia, and
      demonstrated minimal overall cell loss, whilst controls (not preconditioned, but
      exposed to 24 h hypoxia) demonstrated a 44% cell loss. Phosphoimmunoblot analysis
      of pro-survival signaling pathways revealed significant activation of serine
      threonine kinase Akt with DETA-NONOate (p < 0.01) and heat preconditioning (p <
      0.05). DETA-NONOate also activated ERK 1/2 signaling (p < 0.05). In vivo
      implantation: 100,000 preconditioned (heat, hypoxia, or DETA-NONOate) myoblasts
      were implanted in SCID mouse tissue engineering chambers. 100,000 (not
      preconditioned) myoblasts were implanted in control chambers. At 3 weeks,
      morphometric assessment of surviving myoblasts indicated myoblast percent volume
      (p = 0.012) and myoblasts/mm(2) (p = 0.0005) overall significantly increased in
      preconditioned myoblast chambers compared to control, with DETA-NONOate
      preconditioned myoblasts demonstrating the greatest increase in survival (p =
      0.007 and p = 0.001 respectively). DETA-NONOate therefore has potential
      therapeutic benefits to significantly improve survival of transplanted cells.

PMID- 22369962
TI  - Tumor-targeted drug delivery using MR-contrasted docetaxel -
      carboxymethylcellulose nanoparticles.
AB  - A carboxymethylcellulose-based polymer conjugate with nanoparticle forming
      properties (Cellax) has been shown to enhance the pharmacokinetics, specificity
      of biodistribution, anti-tumor efficacy and safety of docetaxel (DTX) in
      comparison to the TaxotereTM formulation. We examined Cellax and Taxotere
      efficacy in four tumor models (EMT-6, B16F10, PC3, and MDA-MB-231), and observed
      variances in efficacy. To explore whether differences in tumor uptake of Cellax
      were responsible for these effects, we incorporated superparamagnetic iron oxide
      nanoparticles (SPIONs) into Cellax particles to enable magnetic resonance (MR)
      imaging (Cellax-MR). In the EMT-6 tumor model, Cellax-MR nanoparticles exhibited
      peak tumor accumulation 3-24 h post intravenous injection, and 3 days post
      treatment, significant MR contrast was still detected. The amount of Cellax-MR
      deposited in the EMT-6 tumors was quantifiable as a hypointense volume fraction,
      a value positively correlated with drug content as determined by LC/MS analysis
      (R(2) = 0.97). In the four tumor models, Cellax-MR uptake was linearly associated
      with anti-tumor efficacy (R(2) > 0.9), and was correlated with blood vessel
      density (R(2) > 0.9). We have affirmed that nanoparticle uptake is variable in
      tumor physiology, and that this efficacy-predictive parameter can be non
      invasively estimated in real-time using a theranostic variant of Cellax.

PMID- 22369963
TI  - Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid
      hydrogel microenvironment.
AB  - An injectable and biodegradable hydrogel system comprising hyaluronic acid
      tyramine (HA-Tyr) conjugates can safely undergo covalent cross-linking in vivo by
      the addition of small amounts of peroxidase and hydrogen peroxide (H(2)O(2)),
      with the independent tuning of the gelation rate and degree of cross-linking.
      Such hydrogel networks with tunable mechanical and degradation properties may
      provide the additional level of control needed to enhance chondrogenesis and
      overall cartilage tissue formation in vitro and in vivo. In this study, HA-Tyr
      hydrogels were explored as biomimetic matrices for caprine mesenchymal stem cells
      (MSCs) in cartilage tissue engineering. The compressive modulus, equilibrium
      swelling and degradation rate could be controlled by varying the concentration of
      H(2)O(2) as the oxidant in the oxidative coupling reaction. Cellular condensation
      reflected by the increase in effective number density of rounded cells in lacunae
      was greater in softer hydrogel matrices with lower cross-linking that displayed
      enhanced scaffold contracture. Conversely, within higher cross-linked matrices,
      cells adopted a more elongated morphology, with a reduced degree of cellular
      condensation. Furthermore, the degree of hydrogel cross-linking also modulated
      matrix biosynthesis and cartilage tissue histogenesis. Lower cross-linked matrix
      enhanced chondrogenesis with increases in the percentage of cells with
      chondrocytic morphology; biosynthetic rates of glycosaminoglycan and type II
      collagen; and hyaline cartilage tissue formation. With increasing cross-linking
      degree and matrix stiffness, a shift in MSC differentiation toward fibrous
      phenotypes with the formation of fibrocartilage and fibrous tissues was observed.
      These findings suggest that the tunable three-dimensional microenvironment of the
      HA-Tyr hydrogels modulates cellular condensation during chondrogenesis and has a
      dramatic impact on spatial organization of cells, matrix biosynthesis, and
      overall cartilage tissue histogenesis.

PMID- 22369964
TI  - Validation of the (Q)SAR combination approach for mutagenicity prediction of
      flavor chemicals.
AB  - Most exposure levels of flavor in food are considered to be extremely low. If at
      all, genotoxic properties should be taken into account in safety evaluations. We
      have recently established a (quantitative) structure-activity relationship,
      (Q)SAR, combination system, which is composed of three individual models of
      mutagenicity prediction for industrial chemicals. A decision on mutagenicity is
      defined as the combination of predictive results from the three models. To
      validate the utility of our (Q)SAR system for flavor evaluation, we assessed 367
      flavor chemicals that had been evaluated mainly by JECFA and for which Ames test
      results were available. When two or more models gave a positive evaluation, the
      sensitivity was low (19.4%). In contrast, when one or more models gave a positive
      evaluation, the sensitivity increased to 47.2%. The contribution of this
      increased sensitivity was mainly due to the result of the prediction by Derek for
      Windows, which is a knowledge-based model. Structural analysis of false negatives
      indicated some common sub-structures. The approach of improving sub-structural
      alerts could effectively contribute to increasing the predictability of the
      mutagenicity of flavors, because many flavors possess categorically similar
      functional sub-structures or are composed of a series of derivatives.

PMID- 22369965
TI  - Antioxidant properties and phenolic profile of the most widely appreciated
      cultivated mushrooms: a comparative study between in vivo and in vitro samples.
AB  - The present study reports a comparison of the antioxidant properties and phenolic
      profile of the most consumed species as fresh cultivated mushrooms and their
      mycelia produced in vitro: Agaricus bisporus (white and brown), Pleurotus
      ostreatus (oyster), Pleurotus eryngii (king oyster) and Lentinula edodes
      (shiitake). The antioxidant activity was evaluated through reducing power (Folin
      Ciocalteu and Ferricyanide/Prussian blue assays), free radical scavenging
      activity (DPPH assay) and lipid peroxidation inhibition (beta-carotene/linoleate
      and TBARS assays). The analysis of phenolic compounds was performed by HPLC/PAD.
      The mushroom species with the highest antioxidant potential was Agaricus bispous
      (brown). However, concerning to the species obtained in vitro, it was L. edodes
      that demonstrate the highest reducing power. Generally, in vivo samples revealed
      higher antioxidant properties than their mycelia obtained by in vitro techniques.
      About the phenolic compounds researched, they were detected both in mushrooms and
      mycelia without any particular abundance. Results showed that there is no
      correlation between the studied commercial mushrooms and the corresponding
      mycelia obtained in vitro. Nevertheless, this study contributes to the rise of
      data relatively to the species consumed as fresh mushrooms and the possibility of
      their in vitro production as a source of bioactive compounds.

PMID- 22369966
TI  - In vivo biological activity of rocket extracts (Eruca vesicaria subsp. sativa
      (Miller) Thell) and sulforaphane.
AB  - Eruca is thought to be an excellent source of antioxidants like phenolic
      compounds, carotenoids, glucosinolates and their degradation products, such as
      isothiocyanates. Sulforaphane is one of the most potent indirect antioxidants of
      Eruca isolated until the date. In this work we investigate: (i) the safety and
      DNA protective activity of Eruca extracts and sulforaphane (under and without
      oxidative stress) in Drosophila melanogaster; and (ii) the influence on D.
      melanogaster life span treated with Eruca extracts and sulforaphane. Our results
      showed that among the four concentrations of Eruca extracts tested (from 0.625 to
      5mg/ml), intermediate concentrations of the Es2 accession (1.25 and 2.5mg/ml)
      exhibited no genotoxic activity, as well as antigenotoxic activity (inhibition
      rate of 0.2-0.6) and the lowest concentration of Es2 and Es4 accessions (0.625
      mg/ml) also enhanced the health span portion of the live span curves.
      Sulforaphane presented a high antigenotoxic activity in the SMART test of D.
      melanogaster and intermediate concentrations of this compound (3.75 MUM) enhanced
      average healthspan. The results of this study indicate the presence of potent
      antigenotoxic factors in rocket, which are being explored further for their
      mechanism of action.

PMID- 22369967
TI  - Structural implication for the impaired binding of W150A mutant LOX-1 to oxidized
      low density lipoprotein, OxLDL.
AB  - Lectin-like oxidized lipoprotein (OxLDL) receptor 1, LOX-1, is the major OxLDL
      receptor expressed on vascular endothelial cells. We have previously reported the
      ligand-recognition mode of LOX-1 based on the crystal structure of the ligand
      binding domain (C-type lectin-like domain, CTLD) and surface plasmon resonance
      analysis, which suggested that the functional significance of the CTLD dimer (the
      'canonical' dimer) is to harbor the characteristic "basic spine" on its surface.
      In this study, we have identified the key inter-domain interactions in retaining
      the canonical CTLD dimer by X-ray structural analysis of the inactive mutant
      W150A CTLD. The canonical CTLD dimer forms through tight hydrophobic
      interactions, in which W150 engages in a lock-and-key manner and represents the
      main interaction. The loss of the Trp ring by mutation to Ala prevents the
      formation of the canonical dimer, as elucidated from docking calculations using
      the crystal structure of W150A CTLD. The results emphasize that the canonically
      formed CTLD dimer is essential for LOX-1 to bind to OxLDL, which supports our
      proposed view that the basic spine surface present in the correctly formed dimer
      plays a primal role in OxLDL recognition. This concept provides insight into the
      pathogenic pattern recognized by LOX-1 as a member of the pattern recognition
      receptors.

PMID- 22369968
TI  - Distal femoral fixation: a biomechanical comparison of retrograde nail,
      retrograde intramedullary nail, and prototype locking retrograde nail.
AB  - BACKGROUND: Distal femur fractures continue to be a complex surgical problem for
      which the incidence is increasing. Presently, there is a need for different
      constructs to address these complex fractures. This study attempts to define the
      biomechanical properties of several implants. METHODS: A novel, prototype locking
      retrograde intramedullary nail and the Russell-Taylor femoral retrograde nail
      were tested at non-destructive, physiological, axial mode load strength using a
      young, synthetic bone model for a medial segmental shaft defect in the
      supracondylar region of the distal femur (medial gap of 10mm, 65mm proximal to
      the distal joint and parallel to the knee axis). Each specimen was compressively
      loaded and unloaded to the peak load for 80,000cycles at a 0.5Hz frequency. These
      were compared to the results from the same lab of the retrograde Trigen
      intramedullary nail. Motion and peak displacement were measured across the
      fracture site as a reflection of construct stability. FINDINGS: Previous testing
      demonstrated that Trigen intramedullary nail had significantly less motion across
      the gap and increased overall stiffness of the construct (P<0.05) compared to
      both Russell-Taylor and prototype nails. INTERPRETATION: Locking technology used
      in a nail biomechanically appears to lead to more micro-motion across the
      fracture gap and to less stiffness in this construct. Further research needs to
      be invested into intramedullary, locking technology before introducing it into
      clinical practice.

PMID- 22369969
TI  - Hedgehog pathway and GLI1 isoforms in human cancer.
AB  - The Hedgehog signaling pathway regulates normal cell growth and differentiation.
      When deregulated, the Hedgehog pathway leads to tumorigenesis and supports more
      aggressive phenotypes of human cancers, such as progression, metastasis, and
      therapeutic resistance. The glioma-associated oncogene homolog 1 (GLI1) family of
      zinc finger transcription factors is the nuclear mediator of the Hedgehog pathway
      that regulates genes essential for various stages of tumor development and
      progression. Consequently, several components of the Hedgehog pathway are major
      targets of cancer therapy, including GLI1 and smoothened. Although the GLI1 gene
      was initially identified as an amplified gene in glioblastoma, its amplification
      was found to be relatively rare. No somatic mutations have been reported in the
      GLI1 gene. Notably, two decades after the discovery of the GLI1 gene, the GLI1
      transcript was recently found to undergo alternative splicing forming two shorter
      isoforms, an N-terminal deletion variant (GLI1DeltaN) and a truncated GLI1
      (tGLI1). These variants appear to have different patterns of tissue expression
      and functions. Most notably, the tGLI1 isoform behaves as a gain-of-function GLI1
      that can induce expression of genes not regulated by GLI1 and promotes more
      aggressive cancer phenotypes. Therefore, this review will focus on the structural
      and functional differences between these isoforms, and also on their
      contributions to important cancer cell characteristics, including proliferation,
      motility, invasion, and angiogenesis.

PMID- 22369971
TI  - Targeting the side effects of steroid therapy in autoimmune diseases: the role of
      GILZ.
AB  - Glucocorticoids are among the most widely prescribed drugs used for human
      diseases, and are especially commonly used in autoimmune diseases. Their use
      reflects their rapid and broad spectrum actions on immune cells, which in turn
      reflect the multiple mechanisms of cell activation upon which glucocorticoids
      impact. While inhibition of pro-inflammatory gene expression is a major effect of
      glucocorticoids, they also induce the expression of numerous molecules that exert
      regulatory influences on the immune system. Among these is glucocorticoid induced
      leucine zipper (GILZ), a recently described, highly glucocorticoid-induced,
      transcriptional regulatory protein which has important inhibitory effects on
      immune and inflammatory cell functions. In this review, we summarize knowledge of
      the actions of glucocorticoids relevant to autoimmune disease, and focus on the
      potential for greater understanding of the function of GILZ to facilitate
      discovery of new therapeutic options for these diseases.

PMID- 22369970
TI  - The interplay of autoimmunity and insulin resistance in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a common chronic disease characterized by selective
      autoimmune destruction of the pancreatic islet beta cells and subsequent
      dependence on exogenous insulin. Certain alleles including the high-risk HLA
      genotype, HLA-DR3-DQ2/DR4-DQ8, place individuals at increased risk of developing
      T1D. Autoantibodies to beta cell antigens are used in the diagnosis of T1D, and
      studies have shown that they can be used to predict risk of developing T1D in
      first degree relatives of probands. The annual global incidence of T1D is
      increasing by 3-5% per year. Many environmental factors have been implicated in
      the rising incidence of T1D. Proponents of the accelerator hypothesis argue that
      T1D and type 2 diabetes (T2D) are the same disorder of insulin resistance,
      although with different genetic backgrounds. While insulin resistance is a
      recognized hallmark of T2D, it also appears to play a significant role in the
      pathogenesis of T1D and its vascular complications. In this article, we will
      review: 1) immunogenetics of T1D, 2) risk factors for the development of islet
      autoimmunity and T1D, 3) mechanisms of insulin resistance in T1D, and 4) links
      between insulin resistance and complications in T1D. Further studies are needed
      to define environmental factors causing T1D as well as the role of insulin
      resistance in the pathogenesis of T1D and its complications.

PMID- 22369972
TI  - Targeting prostate cancer stem cells for cancer therapy.
AB  - Prostate cancer is the most common malignant neoplasm in men and the second most
      frequent cause of cancer death for males in the United States. Recently, emerging
      evidence suggests that prostate cancer stem cells (CSCs) may play a critical role
      in the development and progression of prostate cancer. Therefore, targeting
      prostate CSCs for the prevention of tumor progression and treatment of prostate
      cancer could become a novel strategy for better treatment of patients diagnosed
      with prostate cancer. In this review article, we will summarize the most recent
      advances in the prostate CSCs field, with particular emphasis on targeting
      prostate CSCs to treat prostate cancer.

PMID- 22369973
TI  - Mitochondrial tRNA-serine (AGY) m.C12264T mutation causes severe multisystem
      disease with cataracts.
AB  - Progressive multisystem disease should invoke consideration of potential
      mitochondrial etiologies. Mitochondrial disease can affect any organ system at
      any time, particularly involving neurologic, cardiac, muscular,
      gastroenterologic, and/or ophthalmologic manifestations. We report here a 19-year
      old Caucasian man who was followed since birth in multiple pediatric subspecialty
      clinics for myelomeningocele complications. However, he progressively developed a
      host of additional problems that were not readily attributable to his neural tube
      defect involving developmental, ophthalmologic, cardiac, muscular, endocrine, and
      intermediary metabolic manifestations. Clinical diagnostic testing limited to
      analysis for common point mutations and deletions in his blood mitochondrial DNA
      (mtDNA) was not revealing. Skeletal muscle biopsy revealed abnormal mitochondrial
      morphology and immunostaining, mitochondrial proliferation, and mildly reduced
      respiratory chain complex I-III activity. Whole mitochondrial genome sequencing
      analysis in muscle identified an apparently homoplasmic, novel, m.12264C>T
      transition in the tRNA serine (AGY) gene. The pathogenicity of this mutation was
      supported by identification of it being present at low heteroplasmy load in his
      blood (34%) as well as in blood from his maternal grandmother (1%). The proband
      developed severe nuclear cataracts that proved to be homoplasmic for the
      pathogenic mtDNA m.12264C>T mutation. This case highlights the value of pursuing
      whole mitochondrial genome sequencing in symptomatic tissues in the diagnostic
      evaluation of suspected mitochondrial disease. Furthermore, it is the first
      report to directly implicate a single mtDNA mutation in the pathogenesis of
      ocular cataracts and clearly illustrates the important contribution of normal
      metabolic activity to the function of the ocular lens.

PMID- 22369974
TI  - Macrophage subpopulations in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a heterogeneous group of autoimmune
      disorders defined by a consensus of clinical and laboratory criteria. Much of the
      pathophysiology and therapy of SLE has focused on autoimmune B and T cells of the
      adaptive immune system. Recently, the role of macrophages, part of the innate
      immune system, in SLE pathogenesis has gained attention. The field of immunology
      in general has recently changed in the way that it approaches macrophages. Rather
      than viewing them as a single, concrete whole, it has become clear that different
      subpopulations of macrophages contribute to various immune and non-immune
      processes. Such a nomenclature may provide an ideal framework from which to study
      macrophage pathogenesis in SLE. Studies suggest that M1 subtype macrophages play
      an important inflammatory role in SLE pathogenesis. Further, apparently reduced
      populations of M2a and M2c subtype macrophages may contribute to the lack of anti
      inflammatory activity apparent in the disease. M2b subtype macrophages may
      actually have a role in causing disease directly. Regulatory macrophages have yet
      to be explored thoroughly in SLE, though the presence of a few of their markers
      may mean that they are active in suppressing SLE-related inflammation.

PMID- 22369975
TI  - Closed-loop insulin delivery: towards improved diabetes care.
AB  - The prevalence of type 1 diabetes is escalating worldwide. Novel therapies and
      management strategies are needed to reduce associated morbidity. Aggressive blood
      glucose lowering using conventional insulin replacement regimens is limited by
      the risk of hypoglycemia. Even the most motivated patients may struggle to manage
      day-to-day variability in insulin requirements. The artificial pancreas or closed
      loop insulin delivery may improve outcomes, building on recent technological
      progress and combining continuous glucose monitoring with insulin pump therapy.
      So far, closed-loop prototypes have been evaluated under controlled conditions
      suggesting improved glucose control and a reduced risk of hypoglycemia.
      Limitations include suboptimal accuracy and reliability of continuous glucose
      monitors and delays associated with subcutaneous insulin delivery. Outpatient
      evaluation is required as the next step, leading to deployment into clinical
      practice.

PMID- 22369976
TI  - Advances in medical therapies for Cushing's syndrome.
AB  - Cushing's syndrome (CS) is a heterogeneous disorder of diverse etiologies,
      leading to cortisol excess. Endogenous CS is caused by tumors secreting
      adrenocorticotropin (ACTH) (either eutopically or ectopically), cortisol, or very
      rarely corticotropin-releasing hormone (CRH). Definitive therapy of endogenous CS
      optimally involves tumor resection. Indications for medical therapy include
      acutely ill patients in preparation for surgery, those for whom surgery is not
      indicated (such as patients with unknown tumor location or unresectable lesions,
      and patients unfit for surgery for medical reasons), or patients who remain
      hypercortisolemic postoperatively. In the current article, the published
      literature has been reviewed to summarize data on medical therapies used in CS.
      Several agents are either used "off label" or being studied as potential
      therapies for CS. Medications suppressing adrenal steroidogenesis currently in
      use include ketoconazole, metyrapone, mitotane, or etomidate. In addition, the
      investigational agent LCI699 is under study. Centrally acting agents, which
      suppress ACTH secretion, include cabergoline, octreotide, as well as the
      investigational agents pasireotide, bexarotene, and lapatinib, which are being
      studied in patients with pituitary tumors. Mifepristone, a type 2 glucocorticoid
      receptor antagonist, was recently approved by the FDA as a new therapy for CS.
      Although not definitive at present, medical therapies have an important role in
      the management of CS patients. It is anticipated that understanding the
      pathogenesis of these tumors at a molecular level may spawn the development of
      rationally designed, highly efficacious medical therapies for CS in the future.

PMID- 22369977
TI  - Adults with attention deficit hyperactivity disorder: an investigation of age
      related differences in behavioural symptoms, neuropsychological function and co
      morbidity.
AB  - BACKGROUND: The outcomes of attention deficit hyperactivity disorder (ADHD) have
      been studied extensively in the first decades of life, but less is known about
      ADHD in adulthood. Hence we investigated cross-sectional age-related differences
      in behavioural symptoms, neuropsychological function and severity of co-morbid
      disorders within a clinically referred adult ADHD population. METHOD: We
      subdivided 439 referrals of individuals with ADHD (aged 16-50 years) into four
      groups based on decade of life and matched for childhood ADHD severity. We
      compared the groups on measures of self- and informant-rated current behavioural
      ADHD symptoms, neuropsychological performance, and self-rated co-morbid mood and
      anxiety symptoms. RESULTS: There was a significant age-related reduction in the
      severity of all ADHD symptoms based on informant-ratings. In contrast, according
      to self-ratings, inattentive symptoms increased with age. Neuropsychological
      function improved across age groups on measures of selective attention and
      response inhibition. There was a mild correlation between the severity of
      depression symptoms and increasing age. CONCLUSIONS: This observational study
      suggests that, in adulthood, ADHD symptoms as measured using informant-ratings
      and neuropsychological measures continue to improve with increasing age. However
      the subjective experience of people with ADHD is that their symptoms worsen. This
      dichotomy may be partially explained by the presence of co-morbid affective
      symptoms. The main limitation of the study is that it is cross-sectional rather
      than longitudinal, and the latter design would provide more conclusive evidence
      regarding age-related changes in an adult ADHD population.

PMID- 22369978
TI  - The satisfaction survey that matters.

PMID- 22369979
TI  - Viability, maturation and embryo development in vitro of immature porcine and
      ovine oocytes vitrified in different devices.
AB  - This study was designed to evaluate the effects of vitrification on immature
      porcine and ovine oocytes, collected at a slaughterhouse, by performing
      vitrification in devices with different volumes. Viability was evaluated both
      before and after vitrification and maturation. Immediately after warming, the
      percentage of viable pig oocytes was 81% regardless the type of device, while in
      the control (after oocyte selection) was 95%. The viability of matured pig
      oocytes after warming, vitrified in beveled edge open straws (BES) was 6%, in
      small-open-pulled-straw (SOPS) was 17% and in cryotop was 4%, while the viability
      of the control group was 86%. The viability and maturation results were similar
      with all devices. Embryo development (ED) was observed in fresh porcine oocytes
      with 15% 2-8 cell embryos, 7% morulae and 3% blastocysts, and non-embryo cleavage
      was observed in warmed oocytes. The viability of sheep oocytes immediately after
      warming averaged 90% in all devices, while that of the control (after oocyte
      selection) averaged 95%. The viability of warmed oocytes after maturation was:
      BES 21%, SOPS 30%, cryotop 21% and control group 86%; while maturation values
      were 11, 21, 34 and 70%, respectively. After vitrification, the highest ED was
      achieved with ovine oocytes vitrified in SOPS, with 17% morulae development and
      it was the only device in which blastocysts developed. A direct relationship was
      observed between viability and actin filament integrity in both species.

PMID- 22369980
TI  - Removal of low concentration Cr(VI) from aqueous solution by magnetic-fluids
      fixed bed using the high gradient magnetic separation.
AB  - The focus of this paper was a novel model of Cr(VI) extraction process. The
      original so-called "magnetic-fluids fixed bed" (MFFB), which bridged the solvent
      extraction and the fixed-bed extraction by the theory of the high gradient
      magnetic separation (HGMS), has been explained. The MFFB integrated the
      advantages of the two above mentioned classical extraction methods and overcame
      their drawbacks. The feasibility of this method was studied by extraction
      experiments of Cr(VI) from aqueous solution. The influences of the design of
      ferromagnetic steel wires in magnetic separation column, the pH value of feed
      solution, TBP concentration in magnetic fluids, and flow rate of aqueous solution
      in column were investigated. Under the optimum conditions, the proposed method
      obtained high extraction efficiency with continuous process.

PMID- 22369981
TI  - A method for estimating effective coalescence rates during emulsification from
      oil transfer experiments.
AB  - The Oil Transfer Technique (OTT) was developed by Taisne et al. [1] to measure
      coalescence during emulsification and has been applied since in several studies.
      One of the main drawbacks of this technique is that it only gives a qualitative
      measure of coalescence. This paper proposes a new evaluation method of OTT
      experimental results for estimating qualitative coalescence rates, e.g. for
      investigating the scaling of coalescence with emulsification parameters (such as
      homogenizing pressure, and emulsifier concentration). The method is based on
      comparison with simulated OTT experiments using bivariate Population Balance
      Equation models. Simulations have been performed under a wide variety of
      conditions in order to investigate the influence of assumptions on coalescence
      and fragmentation kernels. These investigations show that the scaling of
      coalescence rates could be determined accurately when the scaling of efficient
      residence time of drops in the active region of homogenization is known. The
      proposed evaluation method is also exemplified by analyzing OTT data from two
      previously published studies.

PMID- 22369982
TI  - Template effect of hydrolysis of the catalyst precursor on growth of carbon
      nanotube arrays.
AB  - Iron catalyst films for the growth of carbon nanotube (CNT) arrays are prepared
      using sol-gel technique during different hydrolytic periods. It is shown that the
      extent of hydrolysis of the catalyst precursor has strong impacts on the size and
      density of iron catalyst particles, which distributed on surface of the film. The
      iron catalysts formed big clusters in the early stage of the hydrolysis, whereas
      the particle size decreased dramatically to approximate 20 nm when the hydrolytic
      duration is as long as 150 h. The reaction between the hydrolytic product of
      ethyl orthosilicate and the iron oxide particles effectively influence the
      structure of catalysts during the process of annealing precursor films and
      reducing the iron oxide particles into iron catalysts. We believe that the
      hydrolytic product limits the mobility of the catalyst particles, preventing them
      from aggregating into big clusters by Ostwald ripening. This catalyst film may be
      utilized to create a template to control the length and quality of CNTs.

PMID- 22369983
TI  - Flower-like surface modification of titania materials by lithium hydroxide
      solution.
AB  - Surface modification of titania materials to give flower-like structures has been
      achieved simply by the treatment in lithium hydroxide aqueous solution under mild
      conditions. The flower-like structured materials were characterized by X-ray
      diffraction, thermogravimetric analysis, and Raman scattering. The analyses
      indicate that the flower-like materials are composed of layered hydrous lithium
      titanate. It is suggested that the unique intercalation behavior of lithium ions
      into titania allows dissolution and re-precipitation of titania to form the
      flower-like structure. The obtained flower-like structure can be retained up to
      700  degrees C, while the crystal phase transforms into Li(4)Ti(5)O(12).

PMID- 22369984
TI  - Morphologic evolution of Au nanocrystals grown in ionic liquid by plasma
      reduction.
AB  - Shape controlled Au nanocrystal growth in ionic liquid has been studied by glow
      discharge plasma reduction. In an 1-butyl-3-methylimidazolium tetrafluoroborate
      ([bmim][BF(4)]) solution with poly(vinyl pyrrolidone) (PVP) as surfactant, Au
      nanocrystals grow from faceted NPs to peanut-like particle aggregates, and
      eventually worm-like nanorods and nanowires as the growth time increases. This
      process is further found to be dependent on the concentration of employed
      surfactant. Based on systematic microscopic analysis and control experiments, a
      polymer-assisted oriented attachment mechanism is proposed to explain the
      observed morphologic evolution. Our work may have great implications for the
      employment of ionic liquids for shape controlled synthesis of nanocrystals.

PMID- 22369985
TI  - 4-Allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione: synthesis,
      experimental and theoretical characterization.
AB  - The title molecule, 4-allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione
      (C(10)H(10)N(4)S), was synthesized and characterized by IR-NMR spectroscopy and
      single-crystal X-ray diffraction. The compound crystallizes in the monoclinic
      space group is P2(1)/c, a=8.006(5)A, b=15.363(5)A, c=8.936(5)A, beta=104.441(5)
      degrees  and V=1064.4(10)A(3), F(000)=456, D(x)=1.362 g/cm(3). In addition to the
      molecular geometry from X-ray experiment, the molecular geometry, vibrational
      frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift
      values of the title compound in the ground state have been calculated using the
      Hartree-Fock (HF) and density functional method (DFT/B3LYP) with 6-31G(d) basis
      set. To determine conformational flexibility, molecular energy profile of the
      title compound was obtained by HF/6-31G(d) and (DFT/B3LYP) calculations with
      respect to selected degree of torsional freedom, which was varied from -180
      degrees  to +180 degrees  in steps of 10 degrees . Besides, molecular
      electrostatic potential (MEP), frontier molecular orbitals (FMO), and several
      thermodynamic properties were performed by the HF and DFT methods.

PMID- 22369986
TI  - Progression of osteoporosis in patients with COPD: a 3-year follow up study.
AB  - Currently, our knowledge on the progression of osteoporosis and its determinants
      is limited in patients with chronic obstructive pulmonary disease (COPD). Bone
      mineral density generally remains stable in patients with COPD over a period of 3
      years. Nevertheless, the progression of vertebral fractures was not assessed,
      while an increase of vertebral fractures over time may be reasonable. Aims of the
      current study were to determine the percentage of newly diagnosed osteoporotic
      patients after a follow up of 3 years and to identify baseline risk factors for
      the progression of osteoporosis in COPD. Clinically stable COPD outpatients were
      included. Lung function parameters, body composition measures, six minute walk
      distance, DXA-scan and X-spine were assessed at baseline and repeated after 3
      years. Prevalence of osteoporosis in COPD patients increased from 47% to 61% in 3
      years mostly due to an increase of vertebral fractures. Lower baseline T-score at
      the trochanter independently increased the risk for the development of
      osteoporosis. Additionally, baseline vitamin D deficiency increased this risk 7.5
      fold. In conclusion, the prevalence of osteoporosis increased over a 3-year
      period in patients with COPD. Baseline risk factors for the development of
      osteoporosis are osteopenia at the trochanter and vitamin D deficiency.

PMID- 22369987
TI  - Evaluation of the Megaduct sweat collector for mineral analysis.
AB  - Accurate measurement of sweat mineral loss is important for whole body mineral
      balance estimates and dietary reference intake formulation. Currently, common
      localized sweat collection methods such as the pouch and patch techniques may be
      limited by skin encapsulation and/or hidromeiosis, which may alter sweat mineral
      concentrations. The design of the newly developed Megaduct sweat collector may
      avoid these possible limitations. Therefore, the purpose of this study was to
      evaluate the utility of the Megaduct sweat collector for mineral analysis.
      Megaduct sweat collectors were affixed to ten volunteers on the final day of a
      heat acclimation protocol; collection time, sweat volume, and mineral
      concentrations of calcium, copper, iron, potassium, sodium, and zinc were
      measured. Megaduct filling required a collection period of 62 +/- 3 min due to a
      small collection surface (22.1 cm(2)). The mineral content of the sweat was 0.3
      +/- 0.1 mmol L(-1), 1.5 +/- 1.5 umol L(-1), 8.5 +/- 2.1 mmol L(-1), 43.2 +/- 15.0
      mmol L(-1), and 10.1 +/- 5.7 umol L(-1) for Ca, Cu, K, Na, and Zn, respectively.
      The Megaduct sweat collector appears to avoid skin encapsulation and
      hidromeiosis, and captures sweat with similar mineral concentrations as reported
      in the literature for pouches. However, the filling time of the Megaduct (>60
      min) may not capture possible changes in sweat mineral concentrations that are
      documented to occur in as little as 15 to 30 min.

PMID- 22369988
TI  - Toxicological and dermatological assessments for two groups of fragrance
      ingredients: 1) aryl alkyl alcohol 2) aryl alkyl alcohols simple acid esters.
      Introduction.

PMID- 22369991
TI  - Exchange interactions and Tc in rhenium-doped silicon: DFT, DFT + U and Monte
      Carlo calculations.
AB  - Interactions between rhenium impurities in silicon are investigated by means of
      the density functional theory (DFT) and the DFT + U scheme. All couplings between
      impurities are ferromagnetic except the Re-Re dimers which in the DFT method are
      nonmagnetic, due to the formation of the chemical bond supported by substantial
      relaxation of the geometry. The critical temperature is calculated by means of
      classical Monte Carlo (MC) simulations with the Heisenberg Hamiltonian. The
      uniform ferromagnetic phase is obtained with the DFT exchange interactions at
      room temperature for the impurities concentration of 7%. With the DFT + U
      exchange interactions, the ferromagnetic clusters form above room temperature in
      MC samples containing only 3% Re.

PMID- 22369989
TI  - Temperature gradients in female reproductive tissues.
AB  - Deep body temperature in mammals is generally but incorrectly regarded as
      uniform. Alterations of temperature in oviducts and preovulatory Graafian
      follicles may play a vital role in gamete maturation, fertilization and early
      embryonic development. At a molecular level, the conformation of regulatory
      proteins is susceptible to changes in temperature. Deviation from physiological
      temperature during IVF procedures could thereby exert a profound influence on
      patterns of gene expression as the embryonic genome unfolds during early cleavage
      stages and act to generate specific anomalies. Systematic studies are urgently
      required. The temperature of internal body organs in mammals such as rabbits and
      humans is widely regarded as uniform, but this is not correct. Temperatures in
      reproductive tissues such as ovaries and oviducts vary according to the stage of
      a menstrual or oestrous cycle. Such changes in temperature are thought to be
      critically involved in the maturation of eggs and spermatozoa and thus in events
      shortly before and after fertilization. Proteins in the cytoplasm and nuclei of
      eggs and very young embryos respond to small shifts in temperature by changing
      their three-dimensional shape. Conformational modifications in regulatory
      proteins in the nucleus would influence patterns of gene expression in developing
      embryos and may, when perturbed, alter the sexual phenotype of an individual. In
      the practical context of IVF, studies are needed of the influence of culturing
      gametes and embryos at different temperatures and ranges of temperature on the
      patterns of gene expression in preimplantation embryos.

PMID- 22369992
TI  - Expression and regulation of chemerin during rat pregnancy.
AB  - BACKGROUND: Chemerin is an adipocytokine that is expressed in different fat
      deposits and has been shown to play an important role in adaptive and innate
      immunity due to its activity as a chemoattractant. Chemerin acts as a ligand for
      the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has
      been shown to regulate the development and metabolic function of adipocytes,
      liver and muscle tissue. OBJECTIVE: There is evidence indicating that several
      adipocytokines play an important role in placenta. This study aimed to
      investigate the regulation of chemerin in rat and human placentas throughout
      gestation. DESIGN AND SETTING: Chemerin was examined in rat and human placentas
      using immunohistochemistry. The chemerin expression pattern in the placenta and
      adipose tissue of female Sprague Dawley rats on days 12, 16, 19 and 21 of
      gestation (each of these days represents a group of 12 rats) was determined using
      TaqMan probe-based quantitative real-time PCR. Rat chemerin serum levels were
      analyzed with ELISA on days 8, 12, 16, 19 and 21 and compared to virgin controls.
      RESULTS: Chemerin expression was detected in the cytoplasm of rat placental
      trophoblastic cells and third trimester human placental cytotrophoblast and
      Hofbauer's cells. The serum chemerin levels of rats decreased significantly as
      gestation progressed. Furthermore, placental chemerin mRNA levels rose
      significantly at day 16 of gestation and decreased significantly towards the end
      of the gestation period. CONCLUSION: Taken together, this data suggests that
      chemerin may be an important regulator of maternal-fetal metabolism and metabolic
      homeostasis during pregnancy.

PMID- 22369993
TI  - Calibrated FMRI.
AB  - Functional magnetic resonance imaging with blood oxygenation level-dependent
      (BOLD) contrast has had a tremendous influence on human neuroscience in the last
      twenty years, providing a non-invasive means of mapping human brain function with
      often exquisite sensitivity and detail. However the BOLD method remains a largely
      qualitative approach. While the same can be said of anatomic MRI techniques,
      whose clinical and research impact has not been diminished in the slightest by
      the lack of a quantitative interpretation of their image intensity, the
      quantitative expression of BOLD responses as a percent of the baseline T2*-
      weighted signal has been viewed as necessary since the earliest days of fMRI.
      Calibrated MRI attempts to dissociate changes in oxygen metabolism from changes
      in blood flow and volume, the latter three quantities contributing jointly to
      determine the physiologically ambiguous percent BOLD change. This dissociation is
      typically performed using a "calibration" procedure in which subjects inhale a
      gas mixture containing small amounts of carbon dioxide or enriched oxygen to
      produce changes in blood flow and BOLD signal which can be measured under well
      defined hemodynamic conditions. The outcome is a calibration parameter M which
      can then be substituted into an expression providing the fractional change in
      oxygen metabolism given changes in blood flow and BOLD signal during a task. The
      latest generation of calibrated MRI methods goes beyond fractional changes to
      provide absolute quantification of resting-state oxygen consumption in micromolar
      units, in addition to absolute measures of evoked metabolic response. This review
      discusses the history, challenges, and advances in calibrated MRI, from the
      personal perspective of the author.

PMID- 22369994
TI  - Rule and similarity in grammar: their interplay and individual differences in the
      brain.
AB  - Previous research on artificial grammar has indicated that the human ability to
      classify sentences or letter strings according to grammaticality relies on two
      types of knowledge. One is a superficial, familiarity-based understanding of a
      grammar the other is the knowledge of rules and critical features underlying a
      grammar. The fundamentally different characteristics of these systems permit an
      analysis of receiver-operating characteristics (ROC), which measures the extent
      to which each type of knowledge is used in grammaticality judgments. Furthermore,
      violations of a grammar can be divided into hierarchical and local violations.
      The present study is the first to combine the use of ROC analyses, fMRI and a
      grammaticality dichotomy. Based on previous neuroimaging studies, it was
      hypothesized that judgments based on rule knowledge, as extracted from individual
      ROC analyses, involve the left inferior frontal gyrus (IFG), whereas similarity
      would involve right IFG, as well as left hippocampal regions. With regards to
      violation types, it was hypothesized that hierarchical violations would recruit
      the opercular part of the left IFG as well as the posterior operculum, whereas
      local violations would bilaterally activate the premotor cortex (PMC). Results
      indicated that for greater reliance on rule knowledge, a ventral part of the left
      PMC was activated for ungrammatical items, whereas other PMC areas show a
      differentiated response for grammaticality for individuals less reliant on
      similarity. The right IFG was related to ungrammatical items as a function of
      similarity. Results are discussed with regards to possible error detection
      systems and differentiated efficiencies for respective classification strategies.

PMID- 22369995
TI  - A framework to integrate EEG-correlated fMRI and intracerebral recordings.
AB  - EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions
      associated with interictal epileptiform discharges (IEDs). This technique enables
      the delineation of the complete epileptiform network, including multifocal and
      deeply situated cortical areas. Before EEG-fMRI can be used as an additional
      diagnostic tool in the preoperative work-up, its added value should be assessed
      in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the
      cortex (ECoG), currently the clinical standard. In this study, we propose a
      framework for the analysis of the SEEG data to investigate in a quantitative way
      whether EEG-fMRI reflects the same cortical areas as identified by the IEDs
      present in SEEG recordings. For that purpose, the data of both modalities were
      analyzed with a general linear model at the same time scale and within the same
      spatial domain. The IEDs were used as predictors in the model, yielding for EEG
      fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the
      electrodes that were involved. Finally, the results of the regression analysis
      were projected on the anatomical MRI of the patients. To explore the usefulness
      of this quantitative approach, a sample of five patients was studied who both
      underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of
      the SEEG analysis were compared to the standard visual review of IEDs in SEEG and
      to the identified seizure onset zone, the resected area, and outcome of surgery.
      SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs
      present in the data of all patients. The electrodes with the highest correlation
      values were in good concordance with the electrodes that showed maximal amplitude
      during those events in the SEEG recordings. These results indicate that the
      analysis of SEEG data at the time scale of EEG-fMRI, using the same type of
      regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD
      areas with a positive hemodynamic response function were closely related to the
      spatial pattern of IEDs in the SEEG recordings in four of the five patients. The
      areas of significant BOLD that were not located in the vicinity of depth
      electrodes, were mainly characterized by negative hemodynamic responses.
      Furthermore, the area with a positive hemodynamic response function overlapped
      with the resected area in three patients, while it was located at the edge of the
      resection area for one. To conclude, the results of this study encourage the
      application of EEG-fMRI to guide the implantation of depth electrodes as
      prerequisite for successful epilepsy surgery.

PMID- 22369996
TI  - The correlation between brain gray matter volume and empathizing and systemizing
      quotients in healthy children.
AB  - The abilities to empathize and to systemize, two fundamental dimensions of
      cognitive style, are characterized by apparent individual differences. These
      abilities are typically measured using an empathizing quotient (EQ) and a
      systemizing quotient (SQ) questionnaire, respectively. The purpose of this study
      was to reveal any correlations between EQ and SQ scores and regional gray matter
      volumes in healthy children by applying voxel-based morphometry to magnetic
      resonance images. We collected MRIs of brain structure and administered
      children's versions of the EQ and SQ questionnaires (EQ-C and SQ-C, respectively)
      to 261 healthy children aged 5-15 years. Structural MRI data were segmented,
      normalized, and smoothed using an optimized voxel-based morphometric analysis.
      Next, we analyzed the correlation between regional gray matter volume and EQ-C
      and SQ-C scores adjusting for age, sex, and intracranial volume. The EQ-C scores
      showed significant positive correlations with the regional gray matter volumes of
      the left fronto-opercular and superior temporal cortices, including the
      precentral gyrus, the inferior frontal gyrus, the superior temporal gyrus, and
      the insula, which are functionally related to empathic processing. Additionally,
      SQ-C scores showed a significant negative correlation with the regional gray
      matter volume of the left posterior parietal cortex, which is functionally
      involved in selective attention processing. Our findings suggest that individual
      differences in cognitive style pertaining to empathizing or systemizing abilities
      could be explained by differences in the volume of brain structures that are
      functionally relevant to empathizing and systemizing.

PMID- 22369997
TI  - Modelling with independent components.
AB  - Independent Component Analysis (ICA) is a computational technique for identifying
      hidden statistically independent sources from multivariate data. In its basic
      form, ICA decomposes a 2D data matrix (e.g. time * voxels) into separate
      components that have distinct characteristics. In FMRI it is used to identify
      hidden FMRI signals (such as activations). Since the first application of ICA to
      Functional Magnetic Resonance Imaging (FMRI) in 1998, this technique has
      developed into a powerful tool for data exploration in cognitive and clinical
      neurosciences. In this contribution to the commemorative issue 20 years of FMRI I
      will briefly describe the basic principles behind ICA, discuss the probabilistic
      extension to ICA and touch on what I think are some of the most notorious loose
      ends. Further, I will describe some of the most powerful 'killer' applications
      and finally share some thoughts on where I believe the most promising future
      developments will lie.

PMID- 22369998
TI  - Treatment of sepsis and ARDS with extracorporeal membrane oxygenation and
      interventional lung assist membrane ventilator in a patient with acute
      lymphoblastic leukemia.
AB  - We report an 18-year-old ice skater with acute lymphoblast leukemia. She
      developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and
      ARDS following chemotherapy-induced severe bone marrow failure. She was
      successfully treated with extraordinary life support  measures, which included
      extracorporeal membrane oxygenation, double lumen lung ventilation for management
      of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU
      treatment and a year of rehabilitation, the patient has fully regained her
      functional status, is now finishing  high school, and is ice skating again.

PMID- 22369999
TI  - PDGF mediates TGFbeta-induced migration during development of the spinous
      process.
AB  - Mechanisms mediating closure of the dorsal vertebrae are not clear. Previously,
      we showed that deletion of TGFbeta type II receptor (Tgfbr2) in sclerotome in
      mice results in failure in the formation of the spinous process, mimicking spina
      bifida occulta, a common malformation in humans. In this study, we aimed to
      determine whether missing dorsal structures in Tgfbr2 mutant mice were due to
      defects in mesenchymal migration and to clarify mechanism of TGFbeta-mediated
      migration. First, we showed that gross alterations in dorsal vertebrae were
      apparent by E16.5days in Tgfbr2 mutants. In addition, histological staining
      showed that the mesenchyme adjacent to the developing cartilage was thin compared
      to controls likely due to reduced proliferation and migration of these cells.
      Next, we used a chemotaxis migration assay to show that TGFbeta promotes
      migration in mixed cultures of embryonic sclerotome and associated mesenchyme.
      TGFbeta stimulated expression of PDGF ligands and receptors in the cultures and
      intact PDGF signaling was required for TGFbeta-mediated migration. Since PDGF
      ligands are expressed in the sclerotome-derived cartilage where Tgfbr2 is deleted
      and the receptors are predominantly expressed in the adjacent mesenchyme, we
      propose that TGFbeta acts on the sclerotome to regulate expression of PDGF
      ligands, which then act on the associated mesenchyme in a paracrine fashion to
      mediate proliferation, migration and subsequent differentiation of the adjacent
      sclerotome.

PMID- 22370000
TI  - SMAD4 is essential for generating subtypes of neurons during cerebellar
      development.
AB  - Cerebellum development involves the coordinated production of multiple neuronal
      cell types. The cerebellar primordium contains two germinative zones, the rhombic
      lip (RL) and the ventricular zone (VZ), which generate different types of
      glutamatergic and GABAergic neurons, respectively. What regulates the
      specification and production of glutamatergic and GABAergic neurons as well as
      the subtypes for each of these two broad classes remains largely unknown. Here we
      demonstrate with conditional genetic approaches in mice that SMAD4, a major
      mediator of BMP and TGFbeta signaling, is required early in cerebellar
      development for maintaining the RL and generating subsets of RL-derived
      glutamatergic neurons, namely neurons of the deep cerebellar nuclei, unipolar
      brush cells, and the late cohort of granule cell precursors (GCPs). The early
      cohort of GCPs, despite being deficient for SMAD4, is still generated. In
      addition, the numbers of GABAergic neurons are reduced in the mutant and the
      distribution of Purkinje cells becomes abnormal. These studies demonstrate a
      temporally and spatially restricted requirement for SMAD4 in generating subtypes
      of cerebellar neurons.

PMID- 22370002
TI  - Proliferation and recapitulation of developmental patterning associated with
      regulative regeneration of the spinal cord neural tube.
AB  - Developmental patterning during regulative regeneration of the chicken embryo
      spinal neural tube was characterized by assessing proliferation and the
      expression of transcription factors specific to neural progenitor and postmitotic
      neuron populations. One to several segments of the thoracolumbar neural tube were
      selectively excised unilaterally to initiate regeneration. The capacity for
      regeneration depended on the stage when ablation was performed and the extent of
      tissue removed. 20% of surviving embryos exhibited complete regulative
      regeneration, wherein the missing hemi-neural tube was reconstituted to normal
      size and morphology. Fate-mapping of proliferative adjacent tissue indicated
      contributions from the opposite side of the neural tube and potentially from the
      ipsilateral neural tube rostral and caudal to the lesion. Application of the
      thymidine analog EdU (5-ethynyl-2'-deoxyuridine) demonstrated a moderate increase
      in cell proliferation in lesioned relative to control embryos, and quantitative
      PCR demonstrated a parallel moderate increase in transcription of proliferation
      related genes. Mathematical calculation showed that such modest increases are
      sufficient to account for the amount of regenerated tissue. Within the
      regenerated neural tube the expression pattern of progenitor-specific
      transcription factors was recapitulated in the separate advancing ventral and
      dorsal fronts of regeneration, with no evidence of abnormal mixing of progenitor
      subpopulations, indicating that graded patterning mechanisms do not require
      continuity of neural tube tissue along the dorsoventral axis and do not involve a
      sorting out of committed progenitors. Upon completion of the regeneration
      process, the pattern of neuron-specific transcription factor expression was
      essentially normal. Modest deficits in the numbers of transcription factor
      defined neuron types were evident in the regenerated tissue, increasing
      particularly in dorsal neuron types with later lesions. These results confirm the
      regulative potential of the spinal neural tube and demonstrate a capacity for re
      establishing appropriate cellular patterning despite a grossly abnormal
      morphogenetic situation.

PMID- 22370003
TI  - BMP and Hedgehog signaling during the development of scleral ossicles.
AB  - Bone development is a complex process, involving multiple tissues and
      hierarchical inductive interactions. The study of skeletal development has
      largely focused on endochondral bones while intramembranous bones, such as the
      scleral ossicles within the avian eye, have received less attention. Our previous
      research directly demonstrated the involvement of sonic hedgehog and suggested
      the involvement of bmp2 and 4 during the development of scleral ossicles. The
      bones of the sclerotic ring are induced by overlying conjunctival papillae at HH
      35 and 36. Here, we examine the spatial and temporal expression patterns of ptc1,
      ihh, bmp2, bmp4 and bmp7. We show that the cells of conjunctival papillae express
      ptc1, ihh and bmp2 at these stages; coincident with shh expression previously
      described. Interestingly, both ihh and ptc1 are also expressed in the mesenchyme
      underlying the papillae unlike shh and bmp2. Bmp4 and bmp7 are not expressed in
      these regions at any stages examined. Furthermore, using Noggin soaked beads
      implanted adjacent to papillae, we provide direct evidence that the BMP family of
      genes are important factors in the development of scleral ossicles. Localized
      inhibition of BMPs in this way causes a reduced expression of ihh in the
      surrounding tissue demonstrating that the BMP and Hedgehog pathways interact. Our
      data also demonstrates that the sclerotic ring has an intrinsic ability to
      compensate for missing elements. The scleral ossicle system provides a unique
      opportunity to investigate the epithelial-mesenchymal induction of
      intramembranous bones of the vertebrate skull.

PMID- 22370001
TI  - Noggin recruits mesoderm progenitors from the dorsal aorta to a skeletal myogenic
      fate.
AB  - Embryonic mesoangioblasts are the in vitro counterpart of vessel-associated
      progenitors, able to differentiate into different mesoderm cell types. To
      investigate signals recruiting these progenitors to a skeletal myogenic fate, we
      developed an in vitro assay, based upon co-culture of E11.5 dorsal aorta (from
      MLC3F-nLacZ transgenic embryos, expressing nuclear beta galactosidase only in
      striated muscle) with differentiating C2C12 or primary myoblasts. Under these
      conditions muscle differentiation from cells originating from the vessel can be
      quantified by counting the number of beta gal+nuclei. Results indicated that
      Noggin (but not Follistatin, Chordin or Gremlin) stimulates while BMP2/4 inhibits
      myogenesis from dorsal aorta progenitors; neutralizing antibodies and shRNA
      greatly reduce these effects. In contrast, TGF-beta1, VEGF, Wnt7A, Wnt3A, bFGF,
      PDGF-BB and IGF1 have no effect. Sorting experiments indicated that the majority
      of these myogenic progenitors express the pericyte marker NG2. Moreover they are
      abundant in the thoracic segment at E10.5 and in the iliac bifurcation at E11.5
      suggesting the occurrence of a cranio-caudal wave of competent cells along the
      aorta. BMP2 is expressed in the dorsal aorta and Noggin in newly formed muscle
      fibers suggesting that these two tissues compete to recruit mesoderm cells to a
      myogenic or to a perithelial fate in the developing fetal muscle.

PMID- 22370004
TI  - The effect of counselling, graded exercise and usual care for people with chronic
      fatigue in primary care: a randomized trial.
AB  - BACKGROUND: To evaluate the effectiveness of graded exercise therapy (GET),
      counselling (COUNS) and usual care plus a cognitive behaviour therapy (CBT)
      booklet (BUC) for people presenting with chronic fatigue in primary care. METHOD:
      A randomized controlled trial in general practice. The main outcome measure was
      the change in the Chalder fatigue score between baseline and 6 months. Secondary
      outcomes included a measure of global outcome, including anxiety and depression,
      functional impairment and satisfaction. RESULTS: The reduction in mean Chalder
      fatigue score at 6 months was 8.1 [95% confidence interval (CI) 6.6-10.4] for
      BUC, 10.1 (95% CI 7.5-12.6) for GET and 8.6 (95% CI 6.5-10.8) for COUNS. There
      were no significant differences in change scores between the three groups at the
      6- or 12-month assessment. Dissatisfaction with care was high. In relation to the
      BUC group, the odds of dissatisfaction at the 12-month assessment were less for
      the GET [odds ratio (OR) 0.11, 95% CI 0.02-0.54, p=0.01] and COUNS groups (OR
      0.13, 95% CI 0.03-0.53, p=0.004). CONCLUSIONS: Our evidence suggests that fatigue
      presented to general practitioners (GPs) tends to remit over 6 months to a
      greater extent than found previously. Compared to BUC, those treated with graded
      exercise or counselling therapies were not significantly better with respect to
      the primary fatigue outcome, although they were less dissatisfied at 1 year. This
      evidence is generalizable nationally and internationally. We suggest that GPs ask
      patients to return at 6 months if their fatigue does not remit, when therapy
      options can be discussed further.

PMID- 22370006
TI  - Cardiac arrest in a 35-year-old pregnant woman with sarcoidosis.

PMID- 22370005
TI  - Sodium sulfide prevents water diffusion abnormality in the brain and improves
      long term outcome after cardiac arrest in mice.
AB  - AIM OF THE STUDY: Sudden cardiac arrest (CA) is one of the leading causes of
      death worldwide. Previously we demonstrated that administration of sodium sulfide
      (Na(2)S), a hydrogen sulfide (H(2)S) donor, markedly improved the neurological
      outcome and survival rate at 24 h after CA and cardiopulmonary resuscitation
      (CPR) in mice. In this study, we sought to elucidate the mechanism responsible
      for the neuroprotective effects of Na(2)S and its impact on the long-term
      survival after CA/CPR in mice. METHODS: Adult male mice were subjected to
      potassium-induced CA for 7.5 min at 37 degrees C whereupon CPR was performed with
      chest compression and mechanical ventilation. Mice received Na(2)S (0.55 mgkg(-1)
      i.v.) or vehicle 1 min before CPR. RESULTS: Mice that were subjected to CA/CPR
      and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed
      neurological function. Cardiac arrest and CPR induced abnormal water diffusion in
      the vulnerable regions of the brain, as demonstrated by hyperintense diffusion
      weighted imaging (DWI) 24 h after CA/CPR. Extent of hyperintense DWI was
      associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological
      outcomes, and poor survival rate at 10 days after CA/CPR. Administration of
      Na(2)S prevented the development of abnormal water diffusion and MMP-9 activation
      and markedly improved neurological function and long-term survival (9/12, P<0.05
      vs. Vehicle) after CA/CPR. CONCLUSION: These results suggest that administration
      of Na(2)S 1 min before CPR improves neurological function and survival rate at 10
      days after CA/CPR by preventing water diffusion abnormality in the brain
      potentially via inhibiting MMP-9 activation early after resuscitation.

PMID- 22370007
TI  - Factors complicating interpretation of capnography during advanced life support
      in cardiac arrest--a clinical retrospective study in 575 patients.
AB  - BACKGROUND: End tidal carbon dioxide (ETCO(2)) monitoring during advanced life
      support (ALS) using capnography, is recommended in the latest international
      guidelines. However, several factors might complicate capnography interpretation
      during ALS. How the cause of cardiac arrest, initial rhythm, bystander
      cardiopulmonary resuscitation (CPR) and time impact on the ETCO(2) values are not
      completely clear. Thus, we wanted to explore this in out-of-hospital cardiac
      arrested (OHCA) patients. METHODS: The study was carried out by the Emergency
      Medical Service of Haukeland University Hospital, Bergen, Norway. All non
      traumatic OHCAs treated by our service between January 2004 and December 2009
      were included. Capnography was routinely used in the study, and these data were
      retrospectively reviewed together with Utstein data and other clinical
      information. RESULTS: Our service treated 918 OHCA patients, and capnography data
      were present in 575 patients. Capnography distinguished well between patients
      with or without return of spontaneous circulation (ROSC) for any initial rhythm
      and cause of the arrest (p<0.001). Cardiac arrests with a respiratory cause had
      significantly higher levels of ETCO(2) compared to primary cardiac causes
      (p<0.001). Bystander CPR affected ETCO(2)-recordings, and the ETCO(2) levels
      declined with time. CONCLUSIONS: Capnography is a useful tool to optimise and
      individualise ALS in cardiac arrested patients. Confounding factors including
      cause of cardiac arrest, initial rhythm, bystander CPR and time from cardiac
      arrest until quantitative capnography had an impact on the ETCO(2) values,
      thereby complicating and limiting prognostic interpretation of capnography during
      ALS.

PMID- 22370008
TI  - Linear and nonlinear tremor acceleration characteristics in patients with
      Parkinson's disease.
AB  - The purpose of the study was to evaluate linear and nonlinear tremor
      characteristics of the hand in patients with Parkinson's disease (PD) and to
      compare the results with those of healthy old and young control subjects.
      Furthermore, the aim was to study correlation between tremor characteristics and
      clinical signs. A variety of nonlinear (sample entropy, cross-sample entropy,
      recurrence rate, determinism and correlation dimension) and linear (amplitude,
      spectral peak frequency and total power, and coherence) hand tremor parameters
      were computed from acceleration measurements for PD patients (n = 30, 68.3 +/-
      7.8 years), and old (n = 20, 64.2 +/- 7.0 years) and young (n = 20, 18.4 +/- 1.1
      years) control subjects. Nonlinear tremor parameters such as determinism, sample
      entropy and cross-sample entropy were significantly different between the PD
      patients and healthy controls. These parameters correlated with the Unified
      Parkinson's disease rating scale (UPDRS), tremor and finger tapping scores, but
      not with the rigidity scores. Linear tremor parameters such as the amplitude and
      the maximum power (power corresponding to peak frequency) also correlated with
      the clinical findings. No major difference was detected in the tremor
      characteristics between old and young control subjects. The study revealed that
      tremor in PD patients is more deterministic and regular when compared to old or
      young healthy controls. The nonlinear tremor parameters can differentiate
      patients with PD from healthy control subjects and these parameters may have
      potential in the assessment of the severity of PD (UPDRS).

PMID- 22370010
TI  - Observation of Griffiths phase in antiferromagnetic La(0.32)Eu(0.68)MnO3.
AB  - We report the Griffiths phase (GP) scenario for isovalent doping in
      antiferromagnetic La(0.32)Eu(0.68)MnO(3). Rietveld refinement of structural data
      displays strong crystal structural distortion. The dc and ac magnetic studies
      nicely demonstrate unambiguous aspects of robust GP. The presence of
      ferromagnetically correlated spin clusters is found above the transition
      temperature, T(N). The disorder-driven phase inhomogeneity is correlated to
      strong structural distortion, giving rise to the GP. This is an unique example in
      manganite where double exchange interaction does not play any role for the
      observed phenomenon.

PMID- 22370009
TI  - Ascl3 marks adult progenitor cells of the mouse salivary gland.
AB  - The Ascl3 transcription factor marks a subset of salivary gland duct cells
      present in the three major salivary glands of the mouse. In vivo, these cells
      generate both duct and secretory acinar cell descendants. Here, we have analyzed
      whether Ascl3-expressing cells retain this multipotent lineage potential in adult
      glands. Cells isolated from mouse salivary glands were cultured in vitro as non
      adherent spheres. Lineage tracing of the Ascl3-expressing cells within the
      spheres demonstrates that Ascl3+ cells isolated from adult glands remain
      multipotent, generating both duct and acinar cell types in vitro. Furthermore, we
      demonstrate that the progenitor cells characterized by Keratin 5 expression are
      an independent population from Ascl3+ progenitor cells. We conclude that the
      Ascl3+ cells are intermediate lineage-restricted progenitor cells of the adult
      salivary glands.

PMID- 22370011
TI  - "Subutex is safe": perceptions of risk in using illicit drugs during pregnancy.
AB  - BACKGROUND: The dominant biomedical discourse stresses the physiological risks to
      the foetus or newborn posed by the prenatal use of illicit drugs. There is also a
      strong moral incentive for pregnant women to abstain from drugs. Yet few
      researchers have explored how pregnant, drug-using women themselves perceive the
      risks involved. The present paper investigates the reasoning by women about risks
      involved in prenatal drug use. Theoretically, a socio-cultural approach to risk
      is taken. METHODS: The paper is based on fourteen ethnographic interviews with
      women who had used illicit drugs during pregnancy (mainly buprenorphine), had
      recently given birth and had regularly used prenatal services during pregnancy.
      The interviews were informal, semi-structured and focused on the women's
      experiences of pregnancy and service use. Each interview lasted about an hour.
      The interviews were transcribed and inductively analysed using thematic coding.
      Risk perceptions were identified in the interviewees' expressions and
      understanding of fears, dangers, threats and worries. RESULTS: The women were not
      primarily concerned about health risks: their greatest fears in connection with
      the prenatal use of illicit drugs were giving birth to a child with withdrawal
      symptoms, child protection interventions and child removal, encountering negative
      attitudes in seeking professional help as well as terminating drug use. The
      interviewees did not see abstaining from drugs as a risk-free option. On the
      contrary, the prospect of a drug-free life was filled with fears linked to
      physical and mental pain and disruptions in significant social bonds. The women
      made use of biomedical and nonprofessional understandings of risks. The women's
      friends and acquaintances played a central role as providers of knowledge about
      risks. CONCLUSION: When providing health education to pregnant women with drug
      problems, professionals should take women's perceptions of risk seriously, treat
      the women respectfully and engage them in dialogue about the risks involved.
      Further studies on pregnant women's perceptions of risk in using illicit drugs
      would be highly valuable.

PMID- 22370012
TI  - Ongoing rubella outbreak among adolescents in Salaj, Romania, September 2011
      January 2012.
AB  - A rubella outbreak has been ongoing in Salaj, Romania since September 2011
      involving 1,840 probable and confirmed cases among mainly unvaccinated
      adolescents. The index case had onset of illness on 6 September 2011. The highest
      number of cases was recorded among 10-14-year-olds and 15-19-year-olds.
      Complications were recorded for 11 cases and included meningitis and arthritis.
      Although the peak has passed, surveillance is being maintained in the region.

PMID- 22370013
TI  - Isolation of NDM-1-producing Klebsiella pnemoniae in Ireland, July 2011.
AB  - We report the identification of New Delhi metallo-betalactamase 1 (NDM-1)
      producing Klebsiella pnemoniae in Ireland. The organism was resistant to multiple
      antibiotic classes, including carbapenems, and PCR and sequencing confirmed the
      presence of the blaNDM-1 gene, carried on a 98 kb plasmid. The organism was
      isolated from an infant, who was born in India and moved to Ireland at the age of
      four months. This is the first reported isolation of an NDM-1-producing
      Enterobacteriaceae strain in Ireland.

PMID- 22370014
TI  - NDM-1 producing Acinetobacter baumannii isolated from a patient repatriated to
      the Czech Republic from Egypt, July 2011.
AB  - We describe the isolation of an NDM-1-producing Acinetobacter baumannii in a
      Czech patient repatriated in July 2011 from Egypt. The infection spread to
      another patient on the same ward. Both isolates showed the same resistance
      pattern and were susceptible only to colistin. They had an identical PFGE pattern
      and belonged to the same sequence type ST 1. Sequencing of the blaNDM gene
      identified the NDM-1 variant of the carbapenemase, surrounded by two copies of
      insertion sequence ISAba125.

PMID- 22370015
TI  - Microbiological and molecular characteristics of carbapenemase-producing
      Klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010.
AB  - We report 570 carbapenemase-producing Klebsiella pneumoniae (CPKP) clinical
      isolates in a 1,040-bed Greek tertiary hospital during 2004 to 2010. The first
      CPKP (VIM-producing) was isolated in September 2004. Despite initial containment,
      VIM producers have become endemic since 2006. KPC-producing K. pneumoniae was
      first isolated in August 2007 from a patient who came from Israel, spread
      rapidly, and outcompeted VIM. Overall, 267 (47%) VIM-producing and 301 (53%) KPC
      producing strains were isolated, including 141 (24.7%) from patients with
      bacteraemia. Two isolates carrying both VIM and KPC were isolated in two
      consecutive months in 2009, but not since. The prevalence of CPKP increased from
      0% in 2003 to 38.3% in 2010 (p<0.0001). All genotyped KPC producers harboured
      blaKPC-2 and belonged to two clones, among which the hyperepidemic Greek clone,
      related to those from the United States and Israel, predominated. Most metallo
      beta-lactamase (MBL) producers carried the blaVIM-1 gene and belonged to several
      clones, whereas all but one isolate with blaVIM-12 were clustered within a five
      month period, arising from one clone. Resistance to non-beta-lactam antibiotics
      was also increased among CPKP. They were almost invariably resistant to
      ciprofloxacin and trimethoprim-sulfamethoxazole. Resistance to colistin increased
      from 3.5% (4/115) in 2008 to 20.8% (25/120) in 2010, and resistance to
      tigecycline also increased. Following reinforcement of infection control
      measures, prevalence of CPKP (mainly KPC) has been reduced since mid-2009 (from
      46% in 2009 to 38.3% in 2010). In view of the exhaustion of available therapies,
      investment in infection control resources and optimal antibiotic use is urgently
      required.

PMID- 22370016
TI  - Emergence and outbreak of carbapenemase-producing KPC-3 Klebsiella pneumoniae in
      Spain, September 2009 to February 2010: control measures.
AB  - This report describes the epidemiological features of the first outbreak caused
      by KPC3 carbapenemase-producing Klebsiella pneumoniae (KPC-3-KP) in Spain and how
      it was effectively controlled. From 16 September 2009 to the end of February
      2010, seven patients infected or colonised with KPC-3-KP were detected. Stool
      surveillance cultures were recovered from patients, doctors, nurses, nursing
      assistants, cleaners and hospital porters working in the affected units. Hand
      swabs were taken from workers and patients' relatives for culturing.
      Environmental samples were also taken. Patients infected or colonised with KPC-3
      KP were placed in single rooms under contact precautions and 4% chlorhexidine
      soap was used for their daily hygiene. Staff attended educational seminars and
      workshops on hand hygiene and isolation of patients. An alcohol-based
      disinfectant was used for surface cleaning and disinfecting. The floor was
      cleaned with a disinfectant containing benzalkonium chloride and
      didecyldimethylammonium. All samples collected were negative for KPC-3-KP. After
      implementing the control measures, no further cases were reported in the affected
      units. All cases had comorbidities, long hospital stay and aggressive/intensive
      antimicrobial treatment. This study emphasises the importance of early
      intensification of infection control to interrupt the transmission of KPC
      producing organisms.

PMID- 22370017
TI  - Experiences from the Shiga toxin-producing Escherichia coli  O104:H4 outbreak in
      Germany and research needs in the field, Berlin, 28-29 November 2011.

PMID- 22370018
TI  - Letter to the editor: Screening for Coxiella burnetii infection during pregnancy:
      pros and cons according to the Wilson and Jungner criteria.

PMID- 22370019
TI  - The Communicable Diseases Threat Report now published every week on the ECDC
      website.

PMID- 22370020
TI  - [Prevalence of tobacco use and associated factors among teenage students in
      Madagascar].
AB  - The available data on the prevalence of tobacco use among teenagers in Madagascar
      are very limited. The aim of this study was to analyze tobacco-use behaviors
      among teenage pupils aged 12 to 18 living in urban and suburban areas of
      Madagascar and to identify the associated risk factors. A cross-sectional
      descriptive study was conducted as part of this research. Probabilistic
      multistage sampling was used to obtain a representative sample. Data were
      collected using an anonymous self-reported questionnaire and computer analyzed
      using SPSS 16. Correlation and logistic regression were used to analyze the risk
      factors. The results show that approximately one third of the 711 pupils (36.3%)
      included in the sample reported that they had tried tobacco. Among them, 25.2%
      were regular users. Nearly 10% had started smoking before the age of 14. Male
      adolescents were found to smoke twice as much as their female counterparts. The
      study found that the key factors associated with tobacco use include: male gender
      (Exp(B)=3,769(95%IC 2,579-5,509), urbanization (Exp(B) = 3,679, 95% IC 2,138
      6,332), age, peer influence, a sense of insecurity at school, and the impact of
      the mass media (films, television). The study found that the family environment
      did not have a significant impact on tobacco use. To conclude, the prevalence of
      smoking among teenage pupils in Madagascar is a significant issue. This paper
      argues that it is important to understand the associated risk factors in order to
      develop a prevention program aimed at reversing the tobacco epidemic in schools.

PMID- 22370021
TI  - Center-level factors and racial disparities in living donor kidney
      transplantation.
AB  - BACKGROUND: On average, African Americans attain living donor kidney
      transplantation (LDKT) at decreased rates compared with their non-African
      American counterparts. However, center-level variations in this disparity or the
      role of center-level factors is unknown. STUDY DESIGN: Observational cohort
      study. SETTING & PARTICIPANTS: 247,707 adults registered for first-time kidney
      transplants from 1995-2007 as reported by the Scientific Registry of Transplant
      Recipients. PREDICTORS: Patient-level factors (age, sex, body mass index,
      insurance status, education, blood type, and panel-reactive antibody level) were
      adjusted for in all models. The association of center-level characteristics
      (number of candidates, transplant volume, LDKT volume, median time to transplant,
      percentage of African American candidates, percentage of prelisted candidates,
      and percentage of LDKT) and degree of racial disparity in LDKT was quantified.
      OUTCOMES: Hierarchical multivariate logistic regression models were used to
      derive center-specific estimates of LDKT attainment in African American versus
      non-African American candidates. RESULTS: Racial parity was not seen at any of
      the 275 transplant centers in the United States. At centers with the least racial
      disparity, African Americans had 35% lower odds of receiving LDKT; at centers
      with the most disparity, African Americans had 76% lower odds. Higher percentages
      of African American candidates (interaction term, 0.86; P = 0.03) and prelisted
      candidates (interaction term, 0.80; P = 0.001) at a given center were associated
      with increased racial disparity at that center. Higher rates of LDKT (interaction
      term, 1.25; P < 0.001) were associated with less racial disparity. LIMITATIONS:
      Some patient-level factors are not captured, including a given patient's pool of
      potential donors. Geographic disparities in deceased donor availability might
      affect LDKT rates. Center-level policies and practices are not captured.
      CONCLUSIONS: Racial disparity in attainment of LDKT exists at every transplant
      center in the country. Centers with higher rates of LDKT attainment for all races
      had less disparity; these high-performing centers might provide insights into
      policies that might help address this disparity.

PMID- 22370023
TI  - Invited commentary.

PMID- 22370022
TI  - Effect of frequent or extended hemodialysis on cardiovascular parameters: a meta
      analysis.
AB  - BACKGROUND: Increased left ventricular (LV) mass is a risk factor for
      cardiovascular mortality in patients with chronic kidney failure. More frequent
      or extended hemodialysis (HD) has been hypothesized to have a beneficial effect
      on LV mass. STUDY DESIGN: Meta-analysis. SETTING & POPULATION: MEDLINE literature
      search (inception to April 2011), Cochrane Central Register of Controlled Trials
      and ClinicalTrials.gov using the search terms "short daily HD," "daily HD,"
      "quotidian HD," "frequent HD," "intensive HD," "nocturnal HD," and "home HD."
      SELECTION CRITERIA FOR STUDIES: Single-arm cohort studies (with pre- and post
      study evaluations) and trials examining the effect of frequent or extended HD on
      cardiac morphology and function and blood pressure parameters. Studies of
      hemofiltration, hemodiafiltration, and peritoneal dialysis were excluded.
      INTERVENTION: Frequent (2-8 hours, >3 times weekly) or extended (>4 hours, 3
      times weekly) HD compared with conventional (<=4 hours, 3 times weekly) HD.
      OUTCOMES: Absolute changes in cardiac morphology and function, including LV mass
      index (LVMI; primary) and blood pressure parameters (secondary). RESULTS: We
      identified 38 single-arm studies, 5 crossover trials, and 3 randomized controlled
      trials. By meta-analysis of 23 study arms, frequent or extended HD significantly
      reduced LVMI from baseline (-31.2 g/m(2), 95% CI, -39.8 to -22.5; P < 0.001). The
      3 randomized trials found a less pronounced net reduction in LVMI (-7.0 g/m(2);
      95% CI, -10.2 to -3.7; P < 0.001). LV ejection fraction improved by 6.7% (95% CI,
      1.6% to 11.9%; P = 0.01). Other cardiac morphologic parameters showed similar
      improvements. There also were significant decreases in systolic, diastolic, and
      mean blood pressure and mean number of antihypertensive medications. LIMITATIONS:
      Paucity of randomized controlled trials. CONCLUSIONS: Conversion from
      conventional to frequent or extended HD is associated with improvements in
      cardiac morphology and function, including LVMI and LV ejection fraction,
      respectively, and several blood pressure parameters, which collectively might
      confer long-term cardiovascular benefit. Trials with long-term clinical outcomes
      are needed.

PMID- 22370024
TI  - Invited commentary.

PMID- 22370025
TI  - Invited commentary.

PMID- 22370026
TI  - Peripherally inserted central catheter usage patterns and associated symptomatic
      upper extremity venous thrombosis.
AB  - OBJECTIVES: Peripherally inserted central catheters (PICCs) may be complicated by
      upper extremity (UE) superficial (SVT) or deep venous thrombosis (DVT). The
      purpose of this study was to determine current PICC insertion patterns and if any
      PICC or patient characteristics were associated with venous thrombotic
      complications. METHODS: All UE venous duplex scans during a 12-month period were
      reviewed, selecting patients with isolated SVT or DVT and PICCs placed <=30 days.
      All UE PICC procedures during the same period were identified from an electronic
      medical record query. PICC-associated DVTs, categorized by insertion site, were
      compared with all first-time UE PICCs to determine the rate of UE DVT and
      isolated UE SVT. Technical and clinical variables in patients with PICC
      associated UE DVT also were compared with 172 patients who received a PICC
      without developing DVT (univariable and multivariable analysis). RESULTS: We
      identified 219 isolated UE SVTs and 154 UE DVTs, with 2056 first-time UE PICCs
      placed during the same period. A PICC was associated with 44 of 219 (20%)
      isolated UE SVTs and 54 of 154 UE DVTs (35%). The rates of PICC-associated
      symptomatic UE SVT were 1.9% for basilic, 7.2% for cephalic, and 0% for brachial
      vein PICCs. The rates of PICC-associated symptomatic UE DVT were 3.1% for
      basilic, 2.2% for brachial, and 0% for cephalic vein PICCs (chi(2)P < .001).
      Univariate analysis of technical and patient variables demonstrated that larger
      PICC diameter, noncephalic insertion, smoking, concurrent malignancy, diabetes,
      and older age were associated with UE DVT (P < .05). Multivariable analysis
      showed larger catheter diameter and malignancy were the only variables associated
      with UE DVT (P < .05). CONCLUSIONS: The incidence of symptomatic PICC-associated
      UE DVT is low, but given the number of PICCs placed each year, they account for
      up to 35% of all diagnosed UE DVTs. Larger-diameter PICCs and malignancy increase
      the risk for DVT, and further studies are needed to evaluate the optimal vein of
      first choice for PICC insertion.

PMID- 22370027
TI  - Invited commentary.

PMID- 22370028
TI  - Type IB and type III endoleak 8 years after endovascular aneurysm repair.

PMID- 22370031
TI  - Regarding "Predictors of neck bleeding after eversion carotid endarterectomy".

PMID- 22370029
TI  - Roles for specialty societies and vascular surgeons in accountable care
      organizations.
AB  - With the passage of the Affordable Care Act, accountable care organizations
      (ACOs) represent a new paradigm in healthcare payment reform. Designed to limit
      growth in spending while preserving quality, these organizations aim to incant
      physicians to lower costs by returning a portion of the savings realized by cost
      effective, evidence-based care back to the ACO. In this review, first, we will
      explore the development of ACOs within the context of prior attempts to control
      Medicare spending, such as the sustainable growth rate and managed care
      organizations. Second, we describe the evolution of ACOs, the demonstration
      projects that established their feasibility, and their current organizational
      structure. Third, because quality metrics are central to the use and
      implementation of ACOs, we describe current efforts to design, collect, and
      interpret quality metrics in vascular surgery. And fourth, because a "seat at the
      table" will be an important key to success for vascular surgeons in these
      efforts, we discuss how vascular surgeons can participate and lead efforts within
      ACOs.

PMID- 22370033
TI  - Regarding "Impact of cilostazol after endovascular treatment for infrainguinal
      disease in patients with critical limb ischemia".

PMID- 22370036
TI  - Regarding "Basilic vein transposition versus biosynthetic prosthesis as vascular
      access for hemodialysis".

PMID- 22370037
TI  - DNA sequence and analysis of a 90.1-kb plasmid in Shiga toxin-producing
      Escherichia coli (STEC) O145:NM 83-75.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains belonging to serogroup O145
      are important emerging food-borne pathogens responsible for sporadic cases and
      outbreaks of hemorrhagic colitis and hemolytic uremic syndrome. A large plasmid
      carried by STEC O145:NM strain 83-75 and named pO145-NM was sequenced, and the
      genes were annotated. pO145-NM is 90,103bp in size and carries 89 open reading
      frames. Four genes/regions in pO145-NM encode for STEC virulence factors,
      including toxB (protein involved in adherence), espP (a serine protease), katP
      (catalase peroxidase), and the hly (hemolysin) gene cluster. These genes have
      also been identified in large virulence plasmids found in other STEC serogroups,
      including O26, O157, O111, and O103. pO145-NM carries the espPalpha subtype that
      is associated with STEC strains that cause more severe disease. Phylogenetic
      analyses of HlyB, EspP, and ToxB in various STEC strains showed a high degree of
      similarity of these proteins in E. coli serotypes O145:NM, O26:H11/H-, O111:NM/H
      , and O157:H7 potentially placing these STEC into a related group.

PMID- 22370038
TI  - Hairy Cell Leukemia and cutaneous involvement.

PMID- 22370039
TI  - Clotting factor activity in thawed Octaplas(r) LG during storage at 2-6 degrees C
      for 6 days from a quality assurance point of view.
AB  - INTRODUCTION: Octaplas(r) LG is a second-generation solvent/detergent-treated
      plasma that offers an additional safety benefit by prion elimination. The
      stability of clotting factors of the new S/D plasma after thawing has not been
      investigated yet. This study intended to measure the time course of fibrinogen,
      FII, FV, FVII, FVIII, FIX, PC, fPS and PI through storage at 2-6 degrees C over 6
      days. MATERIALS AND METHODS: We investigated 20 plasma bags (five bags per blood
      group) and measured fibrinogen, FII, FV, FVII, FVIII, FIX, PC, fPS and PI
      immediately after thawing and after 2, 4, 6, 24, 48, 72, 96, 120 and 144 h
      storage at 2-6 degrees C. Five separate plasma bags were thawed and stored at 2-6
      degrees C for microbiological assessment. After 6 days samples were drawn for
      blood cultures that were incubated for six more days. RESULTS: After 6 days FII,
      FIX and PC showed no significant changes. FV (-16%, p<0.001), FVII (-19%,
      p<0.001), FVIII (-19%, p<0.001), FXI (-13%, p<0.0001) and fPS (-4%, p<0.0007)
      decreased significantly. PI levels were stable at 56%. The microbiological
      investigation showed no bacterial contamination. CONCLUSIONS: In Octaplas(r) LG
      plasma clotting factors decreased slightly through storage of 6 days. PI levels
      were remarkably higher and stable over time in the new Octaplas(r) LG. Stability
      of stored Octaplas(r) LG was limited by the decrease of FVIII to 53%, which may
      warrant storage up to 24h from a quality assurance point of view. This could
      result in reduced plasma wastage and costs for healthcare givers.

PMID- 22370040
TI  - Distribution of gunshot residues--the influence of weapon type.
AB  - Gunshot residue (GSR) analysis is a frequently used forensic method for
      investigating shooting events. In this process, GSR-particles are detected on
      pertinent objects, often the hands of a suspect, with energy dispersive X-ray
      microanalysis in a scanning electron microscope. The question asked in court is
      usually the following: "... has or has not a given shot been fired by the suspect
      (at a certain place and time)?" Unfortunately, this question frequently cannot be
      answered by the analyst. Only the presence or absence of "characteristic" GSR
      particles on the investigated sample can be stated with confidence. All other
      assumptions are inherently biased by many factors that are usually only known by
      the culprit or are generally unknown. In order to draw more profound conclusions
      from GSR analytical results, the dynamics of GSR particles have to be considered,
      i.e., how these particles reach a suspect. Consequently, the formation of the
      plume after firing was investigated for eleven different firearms with high speed
      video analysis. The results show that a vast scope exists between revolvers -
      distributing many particles near the shooter - and e.g. shotguns that are quite
      sealed. These differences between the various weapon types should be considered
      for interpretation of the results of GSR-analysis.

PMID- 22370041
TI  - Utility of multi planar and 3D reconstruction for head injuries in the era of
      multi detector computed tomography.

PMID- 22370042
TI  - Sustainability and optimal control of an exploited prey predator system through
      provision of alternative food to predator.
AB  - In the present paper, we develop a simple two species prey-predator model in
      which the predator is partially coupled with alternative prey. The aim is to
      study the consequences of providing additional food to the predator as well as
      the effects of harvesting efforts applied to both the species. It is observed
      that the provision of alternative food to predator is not always beneficial to
      the system. A complete picture of the long run dynamics of the system is
      discussed based on the effort pair as control parameters. Optimal augmentations
      of prey and predator biomass at final time have been investigated by optimal
      control theory. Also the short and large time effects of the application of
      optimal control have been discussed. Finally, some numerical illustrations are
      given to verify our analytical results with the help of different sets of
      parameters.

PMID- 22370043
TI  - Historical biogeography of the North American glacier ice worm, Mesenchytraeus
      solifugus (Annelida: Oligochaeta: Enchytraeidae).
AB  - North American ice worms are the largest glacially-obligate metazoans, inhabiting
      coastal, temperate glaciers between southcentral Alaska and Oregon. We have
      collected ice worm specimens from 10 new populations, completing a broad survey
      throughout their geographic range. Phylogenetic analyses of 87 individuals using
      fragments of nuclear 18S rRNA, and mitochondrial 12S rRNA and cyctochrome c
      oxidase subunit 1 (CO1) identified 18 CO1 haplotypes with divergence values up to
      ~10%. Phylogeographic interpretations suggest a St. Elias Range, Alaskan ancestry
      from an aquatic mesenchytraeid oligochaete during the early-Pliocene. A gradual,
      northward expansion by active dispersal from the central St. Elias clade
      characterizes a northern clade that is confined to Alaska (with one exception on
      Vancouver Island, British Columbia), while a distinct southern clade representing
      worms from British Columbia, Washington and Oregon was likely founded by a
      passive dispersal event originating from a northern ancestor. The geographic
      boundary between central and southern clades coincides with an ice worm
      distribution gap located in southern Alaska, which appears to have restricted
      active gene flow throughout the species' evolutionary history.

PMID- 22370044
TI  - Interleukin-1 receptor antagonist polymorphism (rs2234663) and periodontitis
      susceptibility: a meta-analysis.
AB  - OBJECTIVE: The results of recent published studies focusing on interleukin-1
      receptor antagonist (IL-1RN) gene variable number of tandem repeats (VNTR)
      polymorphism in periodontitis susceptibility are often conflicting. We performed
      a meta-analysis in order to investigate the potential association of IL-1RN VNTR
      polymorphism with susceptibility to either chronic (CP) or aggressive (AgP)
      periodontitis. DESIGN: Nineteen studies involving a total of 2011 cases and 1719
      controls were searched without any language restriction. Odds ratios (ORs) along
      with their 95% confidence intervals (CIs) were calculated to compare the
      distribution of alleles and genotypes between cases and controls. Both fixed and
      random effects models were used to pool the data. RESULTS: The IL-1RN VNTR
      polymorphism was marginally associated with an elevated risk of CP in overall
      populations (22 versus LL (L means the long alleles): OR=1.47, 95% CI 1.00-2.18,
      p=0.05), and the association was consistently significant in severe CP subgroup
      (OR=4.02, 95% CI 1.84-8.80, p<0.0005). Further stratified analysis restricted to
      Hardy-Weinberg equilibrium studies showed evidence for an increased risk with CP
      in Asians (2 allele versus L allele: OR=1.82, 95% CI 1.31-2.54, p<0.0005),
      however, a decreased risk with AgP in Caucasians (L2 versus LL: OR=0.50, 95% CI
      0.32-0.78, p=0.002). CONCLUSIONS: This meta-analysis suggested that IL-1RN VNTR
      polymorphism might contribute to an increased risk on CP and a decreased risk on
      AgP. However, further well-designed studies with large sample size are needed to
      determine the robustness of these observations in different populations.

PMID- 22370045
TI  - Desmoid tumour of the breast as a manifestation of Gardner's syndrome.
AB  - INTRODUCTION: Desmoid tumours of the breast are rare. Although benign, they can
      mimic breast cancer on physical examination, mammography and breast ultrasound
      and can also be locally invasive. Even though they occur sporadically, they can
      also be seen as a part of Gardner's syndrome. We describe a case of desmoid
      tumour in a woman with Gardner's syndrome where the lesion was mammographically
      occult. PRESENTATION OF CASE: A 63-year old woman presented with four months
      history of a painful left breast lump. She had a screening mammogram seven months
      ago which was normal. She is known to have Gardner's syndrome and had a total
      colectomy, she has also had multiple abdominal desmoids excised in the past. On
      examination there was a 4cm*5cm firm, mobile lump in the left breast. Her
      mammograms in the clinic were also normal. Ultrasound suggested a benign lesion
      of the breast and a core biopsy showed it to be a benign spindle cell lesion. She
      underwent wide local excision of the lump, the intraoperative mammograms of the
      excised specimen also failed to detect the lesion. Histopathology of the excised
      specimen confirmed the tumour to be a benign desmoid tumour. She has now been
      offered radiotherapy and nonsteriodal anti-inflammatory drugs (NSAIDs) to reduce
      her chances of a local recurrence. CONCLUSION: A high index of suspicion and a
      thorough triple examination protocol is necessary to detect rare lesions like a
      desmoid tumour which can masquerade as breast carcinoma.

PMID- 22370046
TI  - Measurement of endogenous acetone and isoprene in exhaled breath during sleep.
AB  - This explorative study aims at characterizing the breath behavior of two
      prototypic volatile organic compounds, acetone and isoprene, during normal human
      sleep and to possibly relate changes in the respective concentration time courses
      to the underlying sleep architecture. For this purpose, six normal healthy
      volunteers (two females, four males, age 20-29 years) were monitored over two
      consecutive nights (the first one being an adaption night) by combining real-time
      proton-transfer-reaction mass spectrometry measurements from end-tidal exhalation
      segments with laboratory-based polysomnographic data. Breath acetone
      concentrations increased overnight in all measurements, with an average relative
      change by a factor of up to 4 (median 2.5). Nighttime concentration maxima were
      usually recorded 2-3 h before lights on. For breath isoprene, a nocturnal
      increase in baseline concentrations of about 74% was observed, with individual
      changes ranging from 36-110%. Isoprene profiles exhibited pronounced
      concentration peaks, which were highly specific for leg movements as scored by
      tibial electromyography. Furthermore, relative to a linear trend, baseline
      isoprene concentrations decreased during the transition from the NREM to the REM
      phase of a complete sleep cycle.

PMID- 22370048
TI  - Morphology of monolayer films on quasicrystalline surfaces from the phase field
      crystal model.
AB  - We present a computational study of the morphology of adsorbed monolayers on
      quasicrystalline surfaces with five- and seven-fold symmetry. The phase field
      crystal model is employed to first simulate the growth of the quasicrystal
      surfaces and then to elastically couple a two-dimensional film to the substrate.
      We find several distinct pseudomorphic phases that depend on the position of
      adsorption sites as well as the strength of the monolayer/substrate interaction,
      and quantify them by computing local order parameters. In qualitative agreement
      with recent experiments using colloids in quasiperiodic light fields, we find
      that the formation of quasicrystalline order is greatly inhibited on seven-fold
      surfaces.

PMID- 22370047
TI  - War and first onset of suicidality: the role of mental disorders.
AB  - BACKGROUND: Suicide rates increase following periods of war; however, the
      mechanism through which this occurs is not known. The aim of this paper is to
      shed some light on the associations of war exposure, mental disorders, and
      subsequent suicidal behavior. METHOD: A national sample of Lebanese adults was
      administered the Composite International Diagnostic Interview to collect data on
      lifetime prevalence and age of onset of suicide ideation, plan, and attempt, and
      mental disorders, in addition to information about exposure to stressors
      associated with the 1975-1989 Lebanon war. RESULTS: The onset of suicide
      ideation, plan, and attempt was associated with female gender, younger age, post
      war period, major depression, impulse-control disorders, and social phobia. The
      effect of post-war period on each type of suicide outcome was largely explained
      by the post-war onset of mental disorders. Finally, the conjunction of having a
      prior impulse-control disorder and either being a civilian in a terror region or
      witnessing war-related stressors was associated with especially high risk of
      suicide attempt. CONCLUSIONS: The association of war with increased risk of
      suicidality appears to be partially explained by the emergence of mental
      disorders in the context of war. Exposure to war may exacerbate disinhibition
      among those who have prior impulse-control disorders, thus magnifying the
      association of mental disorders with suicidality.

PMID- 22370049
TI  - Thermodynamic estimation of minor element distribution between immiscible liquids
      in Fe-Cu-based metal phase generated in melting treatment of municipal solid
      wastes.
AB  - Waste electrical and electronic equipment (WEEE) has become an important target
      in managing material cycles from the viewpoint of not only waste management and
      control of environmental pollution but also resource conservation. This study
      investigated the distribution tendency of trace elements in municipal solid waste
      (MSW) or incinerator ash, including valuable non-ferrous metals (Ni, Co, Cr, Mn,
      Mo, Ti, V, W, Zr), precious group metals (PGMs) originated from WEEE (Ag, Au, Pd,
      Pt), and others (Al, B, Pb, Si), between Fe-rich and Cu-rich metal phases by
      means of simple thermodynamic calculations. Most of the typical alloying elements
      for steel (Co, Cr, Mo, Nb, Ni, Si, Ti, V, and W) and Rh were preferentially
      distributed into the Fe-rich phase. PGMs, such as Au, Ag, and Pd, were enriched
      in the Cu-rich phase, whereas Pt was almost equally distributed into both phases.
      Since the primary metallurgical processing of Cu is followed by an electrolysis
      for refining, and since PGMs in crude copper have been industrially recovered
      from the resulting anode slime, our results indicated that Ag, Au, and Pd could
      be effectively recovered from MSW if the Cu-rich phase could be selectively
      collected.

PMID- 22370050
TI  - Waste management under multiple complexities: inexact piecewise-linearization
      based fuzzy flexible programming.
AB  - To tackle nonlinear economies-of-scale (EOS) effects in interval-parameter
      constraints for a representative waste management problem, an inexact piecewise
      linearization-based fuzzy flexible programming (IPFP) model is developed. In
      IPFP, interval parameters for waste amounts and transportation/operation costs
      can be quantified; aspiration levels for net system costs, as well as tolerance
      intervals for both capacities of waste treatment facilities and waste generation
      rates can be reflected; and the nonlinear EOS effects transformed from objective
      function to constraints can be approximated. An interactive algorithm is proposed
      for solving the IPFP model, which in nature is an interval-parameter mixed
      integer quadratically constrained programming model. To demonstrate the IPFP's
      advantages, two alternative models are developed to compare their performances.
      One is a conventional linear-regression-based inexact fuzzy programming model
      (IPFP2) and the other is an IPFP model with all right-hand-sides of fussy
      constraints being the corresponding interval numbers (IPFP3). The comparison
      results between IPFP and IPFP2 indicate that the optimized waste amounts would
      have the similar patterns in both models. However, when dealing with EOS effects
      in constraints, the IPFP2 may underestimate the net system costs while the IPFP
      can estimate the costs more accurately. The comparison results between IPFP and
      IPFP3 indicate that their solutions would be significantly different. The
      decreased system uncertainties in IPFP's solutions demonstrate its effectiveness
      for providing more satisfactory interval solutions than IPFP3. Following its
      first application to waste management, the IPFP can be potentially applied to
      other environmental problems under multiple complexities.

PMID- 22370051
TI  - Multiple activities of RNA-binding proteins S1 and Hfq.
AB  - In all organisms, RNA-binding proteins participate in modulating all the steps in
      the life cycle of RNA, including transcription, folding, translation and
      turnover. In bacteria, RNA-binding proteins may be specific for a few RNA targets
      (e.g., several ribosomal proteins that recognize both rRNA during ribosome
      assembly and their own mRNAs when acting as highly specific autogenous
      repressors) or function as global regulators implicated in numerous regulatory
      networks. Some RNA-binding proteins combine all these features, and this
      particularly concerns the ribosomal protein S1 and the Sm-like protein Hfq. S1 is
      a key mRNA-binding protein in gram-negative bacteria; it recognizes mRNA leaders
      and provides binding of diverse mRNAs to the ribosome at the initiation step of
      translation. Moreover, S1 is a highly specific autogenous repressor that is able
      to distinguish its own mRNA from all the others. Hfq is recognized as a global
      regulator that facilitates small RNA-mRNA interactions in bacteria; it thereby
      controls the expression of many mRNAs either positively or negatively. In
      addition, these two proteins were reported to affect transcription, RNA
      degradation and other processes. Although they have no sequence specificity, Hfq
      and S1 preferentially bind A/U-rich single-stranded RNA regions; despite this,
      they nevertheless carry out very different tasks in the cell. This review is
      focused on the diversity of functions that can be performed by these abundant RNA
      binding bacterial proteins.

PMID- 22370054
TI  - Acute pancreatitis.

PMID- 22370055
TI  - Complex malformation (Ruggieri-Happle) phenotype with "cutis tricolor" in a 10
      year-old girl.
AB  - The term cutis tricolor describes the combination of congenital hyper- and hypo
      pigmented skin lesions in close proximity to each other in a background of normal
      complexion. It is currently regarded as a twin-spotting phenomenon and today is
      clear that not all cases of cutis tricolor represent one single entity. This
      phenomenon has been reported so far: (a) as an isolated skin manifestation; (b)
      as a part of a complex malformation syndrome (Ruggieri-Happle syndrome - RHS);
      (c) as a distinct phenotype [cutis tricolor parvimaculata]; (d) in association
      with other (e.g., vascular) skin disturbances. We report a novel case of cutis
      tricolor in a 10-year-old girl who had dysmorphic facial features [alike those
      seen in cases with syndromic (RHS) cutis tricolor], overall overgrowth [weight,
      length, and head circumference were >90th percentile; there was increased bone
      age], mild cognitive delay (current IQ=55), behavioural disturbances, febrile
      seizures and (later) partial complex epilepsy (currently under good control), and
      skeletal defects [i.e., posterior scalloping of the lumbar vertebrae]. We discuss
      the main similarities and differences between the various phenotypes in the
      spectrum of cutis tricolor and with other conditions sharing features with the
      present case.

PMID- 22370056
TI  - Comments on the article by Mizuno Y. et al. entitled "Congenital infection-like
      syndrome with intracranial calcification".

PMID- 22370057
TI  - A modest proposal for a clinical trial on single-bundle versus double-bundle
      anterior cruciate ligament reconstruction.

PMID- 22370058
TI  - Iatrogenic labral puncture of the hip is avoidable.

PMID- 22370060
TI  - Single-bundle versus double-bundle reconstruction for anterior cruciate ligament
      rupture: a meta-analysis--does anatomy matter?
AB  - PURPOSE: To determine whether double-bundle anterior cruciate ligament
      reconstruction leads to better restoration of anterior and rotational laxity and
      range of motion than single-bundle reconstruction. METHODS: A search was
      performed in the Medline, Embase, CINAHL, and Cochrane databases. All randomized,
      quasi-randomized, and observational clinical trials that reported the outcome of
      double- versus single-bundle anterior cruciate ligament reconstruction were
      included in our meta-analysis. The primary outcomes were anterior laxity (KT
      arthrometer; MEDmetric, San Diego, CA), pivot shift, and range of motion.
      Subgroup analyses were performed for more than 2 years' follow-up, anatomic
      reconstruction, and nonanatomic reconstruction. The quality of the included
      studies was scored by use of the GRADE Checklist. RESULTS: Included 12 studies in
      this meta-analysis, 5 of which were randomized. There was a statistically
      significant difference in favor of double-bundle reconstruction for anterior
      laxity (KT arthrometer difference, -0.6 mm), Lachman test (64% risk reduction of
      positive Lachman), and pivot-shift test (69% risk reduction of positive shift).
      Similar results were found for the subgroup with more than 2 years' follow-up and
      anatomic reconstructions. There were no significant differences for the subgroup
      with nonanatomic reconstructions, except a 2.6 times risk increase of extension
      deficit with nonanatomic double-bundle reconstruction compared with nonanatomic
      single-bundle reconstruction. Most of the included studies were found to have at
      least one serious limitation in study design. CONCLUSIONS: In comparison with
      single-bundle reconstruction, double-bundle reconstruction showed less anterior
      laxity, as measured by the KT arthrometer and Lachman test, and better rotational
      laxity, as measured by the pivot-shift test. The majority of the included studies
      had at least one major limitation in study design that decreased the quality of
      the study. LEVEL OF EVIDENCE: Level I, meta-analysis.

PMID- 22370061
TI  - Technique for Resonance(r) stent exchange in patients with extrinsic obstruction:
      description of a novel approach and literature review.
AB  - Malignant ureteral obstruction is a morbid diagnosis and can be difficult to
      manage. Ureteral stents often fail as the disease progresses. Metallic stents
      have provided a longer-term option for decompression as they inherently resist
      compression and require changes left often. However, changing metallic stents is
      challenging as it cannot be done over a wire as is done with plastic stents. We
      present a novel technique for safe and efficient exchange of the Resonance((r))
      metallic stent. We also review the literature on metallic stents.

PMID- 22370062
TI  - 2q34-qter duplication and 4q34.2-qter deletion in a patient with developmental
      delay.
AB  - The 2q3 duplication and 4q3 deletion syndromes are two conditions with variable
      phenotypes including Pierre-Robin sequence (PRS), limb anomalies, congenital
      heart defects (CHD), developmental delays and intellectual disabilities. We
      describe a patient born to a mother with a balanced t(2; 4) translocation who
      combines both a 2q34-qter duplication and a 4q34.2-qter deletion through
      inheritance of the derivative chromosome 4 (der(4)). He showed developmental
      delay, growth retardation, hearing problems, minor facial and non-facial
      anomalies, such as bilateral fifth finger shortness and clinodactyly, but no PRS
      or CHD. The comparison of his features with those of 46 and 65 published cases of
      2q3 duplication and 4q3 deletion, respectively, allows us to further restrict the
      size of the proposed critical intervals for PRS and CHD on chromosome 4.

PMID- 22370063
TI  - Anxiety sensitivity cognitive concerns predict suicidality among smokers.
AB  - BACKGROUND: Anxiety along with anxiety-related risk factors is receiving
      increased attention in regard to its role in elevated suicidality. One such risk
      factor, anxiety sensitivity (AS), refers to a fear of anxiety-related symptoms.
      Emerging research indicates that components of AS, particularly the AS subfactor
      focused on cognitive arousal concerns, are significantly associated with elevated
      suicidality in samples of diverse clinical outpatients, clinical outpatients with
      PTSD symptoms, and Air Force cadets undergoing a stressful life experience.
      Cigarette smokers represent another relevant population for this line of research
      due to recent reports indicating that cigarette smoking and nicotine dependence
      may be related to elevated suicidality. METHODS: Study 1 examined the role of AS
      and the AS subfactors in a large sample (n=343) of community adult smokers. Study
      2 examined the role of AS and AS subfactors in a sample of "pack-a-day" adult
      smokers (n=78) who were seeking outpatient treatment for substance abuse issues.
      RESULTS: Study 1 results were consistent with our a priori hypothesis that AS
      cognitive concerns would be significantly associated with suicidality.
      Additionally, after covarying for relevant substance use variables, Study 2
      results were also consistent with our hypothesis that AS cognitive concerns were
      significantly associated with suicidality. LIMITATIONS: Limitations included the
      use of suicide related outcomes, not death by suicide, and cross-sectional
      design. CONCLUSIONS: These findings suggest that suicide potential in cigarette
      smokers may be related to AS cognitive concerns and add to the emerging
      literature suggesting AS cognitive concerns are a risk factor for suicidality.

PMID- 22370064
TI  - Do psychiatric medications, especially antidepressants, adversely impact maternal
      metabolic outcomes?
AB  - BACKGROUND: Psychiatric illnesses, particularly depression, are some of the most
      common complications of pregnancy. Accordingly, pharmacologic treatment of these
      illnesses is prevalent and increasing. Systematic reviews on psychiatric
      medication use during pregnancy have shown effects on obstetrical and neonatal
      outcomes and non-systematic reviews of maternal outcomes suggest higher weight
      gain and an increased risk of gestational diabetes. However, to date there has
      not been a systematic review of the effects of these medications on maternal
      metabolic outcomes. OBJECTIVE: The objective of this study was to assess the
      relationship between psychiatric medication use during pregnancy and adverse
      maternal metabolic outcomes [gestational weight gain (GWG), gestational diabetes
      (GDM) and postpartum weight retention (PPWR)]. STUDY DESIGN: Systematic review
      and meta-analysis were used. We searched Medline, EMBASE, PsychInfo and
      references. Two reviewers independently performed each step of the systematic
      review, following the MOOSE guidelines. RESULTS: Of 3080 non-duplicate titles and
      abstracts, 175 articles underwent full text review. Two moderate quality cohort
      studies were included. No differences were found for GWG, GDM and PPWR.
      LIMITATIONS: There were only two studies which met our inclusion criteria, making
      it difficult to make any definitive conclusions regarding the effects of
      psychiatric medication on maternal metabolic outcomes. CONCLUSIONS: Despite the
      suggestions in non-systematic reviews that psychiatric medication use during
      pregnancy results in adverse maternal metabolic sequelae, in this systematic
      review, we found no evidence of an increased risk of GWG, GDM or PPWR in women
      with psychiatric illness who took psychiatric medications compared to non
      medicated women with psychiatric illness. However, more, high quality studies are
      needed in this area to determine if there is an association between psychiatric
      medication use and maternal metabolic outcomes.

PMID- 22370065
TI  - Differential expression of prostaglandin D2 synthase (PTGDS) in patients with
      attention deficit-hyperactivity disorder and bipolar disorder.
AB  - BACKGROUND: As marker genes for bipolar disorder (BP) and attention deficit
      hyperactivity disorder (ADHD) are not fully identified, we carried out a complete
      genome analysis to search for genes differentially expressed in ADHD and BP.
      MATERIALS AND METHODS: We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23
      years. For evaluation of the psychiatric diagnosis, we used a semi-structured
      interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral
      blood and analyzed with the GeneChip(r) Human Genome U133-Plus 2.0 (Affymetrix).
      For the validation of differentially expressed genes, real-time PCR was used.
      RESULTS: Hybridization and subsequent statistical analysis found 502 probe-sets
      with significant differences in expression in ADHD and BP patients. Of these, 82
      had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB,
      CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative
      mRNA determination. The expression of PTGDS was statistically increased in ADHD
      relative to BP patients (p=0.01). We found no such differential expression with
      NRG1, CTSB and CTSD genes (p>0.05). CONCLUSIONS: The gene coding for PTGDS was
      found to be more expressed in patients with ADHD relative to patients with BP,
      indicating a possible link with the differential etiology of ADHD. The
      experimental approach we have used is, at least in part, validated by the
      detection of proteins directly concerned with brain functions, and shows a
      possible way forward for studies of the connection between brain function genes
      and psychiatric disorders. LIMITATIONS: Confirmation of our findings requires a
      larger sample of patients with clearly-defined phenotypes.

PMID- 22370067
TI  - Early and late onset depression in young and middle aged adults: differential
      symptomatology, characteristics and risk factors?
AB  - BACKGROUND: Early onset depression (EOD) and late onset depression (LOD) may be
      different phenomena. In this study, differences between EOD and LOD in
      symptomatology, psychiatric characteristics and psychosocial/somatic factors were
      examined. METHODS: Baseline data were from 1104 participants with a current major
      depressive disorder participating in the Netherlands Study of Depression and
      Anxiety (age range 18-65 years). DSM-IV diagnoses, depressive symptoms and age of
      onset were assessed with the Composite International Diagnostic Interview.
      Analyses were performed by using a continuous as well as a dichotomous (cut-off
      40 years) age of onset indicator. RESULTS: Differences between EOD and LOD were
      observed: longer duration of symptoms (p<.001), a personal history of depressive
      episodes (p<.001), a serious suicide attempt (p<.001), childhood events (p<.001),
      a family history of depression (p=.03), and high neuroticism (p<.001) were more
      often present in EOD than in LOD. Also differences in symptomatology were
      observed: feelings of sadness (p<.001), diminished concentration (p=.02) and
      suicidal thoughts (p=.001) were significantly less prevalent at a higher age of
      onset, whereas decreased appetite/weight loss (p=.01) was more prominent at a
      higher age of onset. LIMITATIONS: The age of first depression onset was asked
      retrospectively and might be biased by selective recall. However, participants
      can likely recall whether symptoms started earlier or later in life. CONCLUSIONS:
      Despite similarities, our observed differential findings in symptoms, psychiatric
      characteristics, and psychosocial factors between EOD and LOD further support
      that EOD is associated with more frequent occurrence of some clinical features of
      depression. These differential findings are important factors to keep in mind for
      diagnostics, treatment, and prevention.

PMID- 22370066
TI  - Family-based association study of early growth response gene 3 with child bipolar
      I disorder.
AB  - BACKGROUND: The risk for relapse of child bipolar I disorder (BP-I) is highly
      correlated with environmental factors. Immediate early genes of the early growth
      response (EGR) gene family are activated at high levels in the brain in response
      to environmental events, including stress, and mediate numerous neurobiological
      processes that have been associated with mental illness risk. The objective of
      this study is to evaluate whether single nucleotide polymorphisms (SNPs) in EGR
      genes are associated with the risk to develop child bipolar I disorder. METHODS:
      To investigate whether EGR genes may influence susceptibility to child bipolar I
      disorder (BP-I), we used Family Based Association Tests to examine whether SNPs
      in each of the EGR genes were associated with illness in 49 families. RESULTS:
      Two SNPs in EGR3 displayed nominally significant associations with child BP-I
      (p=0.027 and p=0.028); though neither was statistically significant following
      correction for multiple comparisons. Haplotype association analysis indicated
      that these SNPs are in linkage disequilibrium (LD). None of the SNPs tested in
      EGR1, EGR2, or EGR4 was associated with child BP-I. LIMITATIONS: This study was
      limited by small sample size, which resulted in it being underpowered to detect a
      significant association after correction for multiple comparisons. CONCLUSIONS:
      Our study revealed a preliminary finding suggesting that EGR3, a gene that
      translates environmental stimuli into long-term changes in the brain, warrants
      further investigation for association with risk for child BP-I disorder in a
      larger sample. Such studies may help reveal mechanisms by which environment can
      interact with genetic predisposition to influence this severe mental illness.

PMID- 22370068
TI  - Reducing attentional capture of emotion by broadening attention: increased global
      attention reduces early electrophysiological responses to negative stimuli.
AB  - Decades of research has shown the influence of emotion on attentional capture,
      and more recently, the influence of emotion on neurophysiological processes
      related to attentional capture. The current research tested whether some of the
      earliest neurophysiological underpinnings of emotive attentional processes can be
      influenced by attentional manipulations of broadening versus narrowing. Previous
      research has shown that negative affects high in motivational intensity (e.g.,
      disgust, fear) cause a relative narrowing of attentional scope (Gable and Harmon
      Jones, 2010a; Easterbrook, 1959). Because of the strong link between motivation
      and attention, attentional scope should also influence the attentional capture of
      negative stimuli. The current study manipulated a local attentional scope or
      global attentional scope, then measured attentional capture towards disgust and
      neutral pictures using the N1 event-related potential component. Results revealed
      that a manipulated global attentional scope reduced N1 amplitude towards disgust
      pictures compared to a manipulated local attentional scope.

PMID- 22370069
TI  - [The interest of public health in mental health].

PMID- 22370070
TI  - [Psychiatry and mental health: dynamics and renewal].

PMID- 22370071
TI  - [The current state of mental health surveillance in France].
AB  - The purpose of health surveillance is to contribute to health planning,
      information and prevention. Surveillance involves repeated data collections based
      on epidemiological studies and follow-up of data collected from medical
      administrative databases. This paper provides an overview of mental health
      surveillance in France and examines the relevance and limitations of the
      collected data. METHOD: The prevalence of major depressive episodes (MDE) in the
      general population was recently examined in seven studies. Among these studies,
      the Health Barometers involved two data collections at a five-year interval using
      the same method. Mortality and hospitalization data are important for suicide and
      suicide attempt (SA) surveillance. Health insurance databases provide key
      information about psychotropic drug use and serious psychiatric illnesses defined
      as long-term. RESULTS: The prevalence of 12-month MDE remained stable at 7.8%
      between 2005 and 2010. Mortality data show a suicide rate of 16 per 100,000
      inhabitants. Hospital data show that the rate of hospitalization for SAs is
      approximately ten times that of suicide. Data from emergency wards indicate that
      approximately 220,000 SAs are admitted to hospital emergency services every year.
      Currently, depressive disorders are the primary reason for new admissions under
      the ALD23. DISCUSSION: A comparison of data from different sources is required to
      provide a basis for mental health surveillance in France and to help identify
      those populations that need to be targeted as a matter of priority by prevention
      measures.

PMID- 22370072
TI  - [Analysis of the reliability of diagnostic criteria and classifications in
      psychiatry].
AB  - The future development of mental health funding in France will be based primarily
      on administrative data and a diagnostic classification: ICD-10. OBJECTIVE: The
      objective of this study was to investigate the inter-rater reliability of
      diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder and
      unipolar depression based on the ICD-10 classification. A cross-sectional study
      was conducted on all of the patients admitted to a public psychiatric hospital on
      the same day in January 2010. Cohen's kappa coefficient was used to estimate
      inter-rater reliability and diagnostic congruence between the treating
      psychiatrist and an independent psychiatrist using a standardized interview. In
      total, 112 patients participated in the study. 56.3% of participants were male
      and the mean age was 43.4 years (SD = 15.0). The proportion of discordant
      diagnoses ranged from 14.3% (schizophrenia and bipolar disorder) to 42.9%
      (schizophrenia and schizoaffective disorder). The coefficient of congruence was
      0.48 for schizoaffective disorder, 0.56 for unipolar depression, 0.80 for
      schizophrenia and 0.90 for bipolar disorder. The reliability of schizoaffective
      disorder and unipolar depression diagnoses may seem limited. Further research on
      larger samples is needed to confirm the results of this study and to determine
      the impact of poor diagnostic reliability on future mental health funding in
      France.

PMID- 22370073
TI  - [A comparative study of coding and information systems for the evaluation of
      medical and social conditions: the case of addictive disorders].
AB  - The purpose of this study was to conduct a descriptive and comparative analysis
      of the tools used by healthcare professionals specializing in addictive disorders
      to promote a rapprochement of information systems. The evaluation guide used to
      assess the compensation needs of disabled persons treated in "Maisons
      Departementales des Personnes Handicapees" (centres for disabled people)
      organizes information in different areas, including a psychological component.
      The guide includes social and environmental information in the "Recueil Commun
      sur les Addictions et les Prises en charges" (Joint Report on Drug Addiction and
      Drug Treatment).   While the program for the medicalization of information
      systems includes care data, the current information about social situations
      remains inadequate.   The international classification of diseases provides
      synthetic diagnostic codes to describe substance use, etiologic factors and the
      somatic and psychological complications inherent to addictive disorders.   The
      current system could be radically simplified and harmonized and would benefit
      from adopting a more individualized approach to non-substance behavioral
      addictions. The international classification of disabilities provides tools for
      evaluating the psychological component included in the recent definition of
      addictive disorders.   Legal information should play an integral role in the
      structure of the information system and in international classifications.   The
      prevalence of episodes of care and treatment of addictive and psychological
      disorders was assessed at Nice University Hospital in all disciplines. Except in
      addiction treatment units, very few patients were found to have a RECAP file.

PMID- 22370074
TI  - [Social inequalities in mental health among employees: results of the Samotrace
      study (France)].
AB  - Social inequalities in mental disorders have been reported. Studies indicate that
      the lower the social position, the higher the prevalence of mental disorders.
      However, these inequalities have not always been observed and results may vary
      according to the examined indicator of social position and mental health
      outcomes. The objective of this study was to examine the link between social
      position (educational level and occupation) and mental disorders (psychological
      distress measured using the GHQ-28 scale and its four sub-dimensions, i.e.
      depressive, anxiety, and somatic symptoms and social dysfunction, psychotropic
      drug use, alcohol abuse, and tobacco status) in a random sample of 6,056 male and
      female employees in the Centre, Pays-de-Loire, and Poitou-Charentes regions of
      west-central France. A high prevalence of depressive symptoms and psychotropic
      drug use was found among low-educated employees and blue-collar workers. However,
      these results did not persist after adjustment for age and classical risk factors
      for mental disorders (marital status, social support, life events and family
      history of depression). Strong social gradients were observed for smoking; these
      social differences persisted after adjustment. Inverse social gradients were
      observed and persisted after adjustment: more educated employees and
      professionals/managers were found to be at higher risk of psychological distress,
      especially anxiety and somatic symptoms and social dysfunction (particularly
      men). This study suggests that classical risk factors for mental health outcomes
      may be socially graded and may account at least in part for the social
      inequalities observed in depressive symptoms and psychotropic drug use.

PMID- 22370075
TI  - [Strategic decisions in public psychiatric institutions: a proposed method for
      resource analysis and allocation].
AB  - Because of its sector-based organization and extra-hospital care, public
      psychiatry has a unique position in healthcare. This paper describes the tools
      and procedures used to analyze and allocate the resources of the "Centre
      Hospitalier Alpes-Isere", a hospital serving a catchment population of 530,000
      adults. A consensus-based approach was used to validate the selected indicators
      and included the participation of a geographer.   Five levels of resource
      allocation were identified and classified using a decision tree. At each level,
      the relevant authorities and criteria were identified as key components of the
      decision-making process. This paper describes the first three levels of care
      provision. Focusing on adult care, a comparative assessment of the resources
      allocated to general psychiatric care and specialist care was conducted, in
      addition to a comparative assessment of the resources allocated to each of the
      hospital's four local centers. Geographical accessibility to extramural
      facilities was also assessed. A study of the characteristics of each general
      psychiatry clinic revealed significant disparities.   The paper highlights
      several issues: the poor knowledge of psychiatric epidemiological data relating
      to the population within the catchment area, the difficulty of assessing non
      consolidated data or indicators from multiple sources, and the limited and
      partial nature of geographical data for characterizing and evaluating health care
      in the hospital's peripheral clinics.   Several studies are currently underway to
      assess the operational effectiveness of the tools and procedures used to analyze
      and allocate resources.

PMID- 22370076
TI  - [Mental health, vulnerability and general practice: a study of non-profit health
      centers in Grenoble].
AB  - Very little research has been conducted on the role of general practitioners
      (GPs) in mental health care among socioeconomically disadvantaged populations in
      France. The non-profit community health care centers in Grenoble provide
      populations living in sensitive urban zones with high quality primary health care
      that includes a medico-social and prevention dimension. The aim of this study was
      to measure the prevalence of mental health issues diagnosed by GPs in health care
      centers, to identify the factors associated with these issues and to describe
      treatment characteristics.   This cross-sectional study focused on general
      practice consultations in the AGECSA Grenoble health care centers over the course
      of one week. At the end of each consultation, the GP collected information about
      the patient, including personal data, psychological disorders, vulnerability, and
      patient health management. Among the 451 patients included in the study, GPs
      found that 45.2% of patients were in vulnerable situations and 43% of patients
      suffered from a mental disorder, including 29% of cases of anxiety and 20% of
      cases of depression. 44% of patients suffered from a psychological disorder
      (mental disorder and/or psychological suffering). For these patients, 52.8% of
      the consultations lasted more than 20 minutes. Their treatment generally included
      a mental health care follow-up (in 76% of cases), including psychological support
      (59%) and treatment of functional somatic disorders (46%). The study shows the
      high prevalence of psychological disorders diagnosed in the patients treated by
      GPs working in health care centers in disadvantaged urban areas. Research shows
      that GPs play an important and specific role in mental health care and
      prevention. An analysis of the organizational methods used in health care centers
      is highly relevant.

PMID- 22370077
TI  - [Evidence-based interventions in youth mental health prevention and promotion].
AB  - The purpose of this paper is to review the current scientific knowledge on mental
      health promotion interventions aimed at children and adolescents. Definitions of
      mental health, mental health prevention and mental health promotion are provided.
      The current state of knowledge in this area was assessed based on a specific
      method involving selection, a literature review and a classification of mental
      health promotion interventions identified using scientific databases. Seventeen
      interventions were identified as having an effect on youth mental health. Half of
      these interventions are aimed at the general population, while the other half
      target vulnerable individuals. The majority of the interventions are aimed at
      children aged 5 and over. Half of the interventions are multimodal, while
      unimodal interventions include programs aimed at promoting psychosocial
      competencies in children. An increased understanding of internationally
      recognized programs should promote reflection on current professional practice in
      France.

PMID- 22370078
TI  - [Key elements of the evolution of adolescent mental health policies].
AB  - The purpose of this study was to examine the evolution of public policies in the
      area of adolescent mental health in France. An analysis of statutory texts,
      public reports and government action plans shows that the mental health policy
      implemented in the early 1990s resulted in a significant expansion of the issues
      and populations needing treatment based on new procedures and frameworks. The
      analysis shows that as a result of the emergence of a new conception of care, a
      sector or network approach has been replaced by a personal route approach aimed
      at supporting teenagers and promoting successful socialization and increased
      autonomy. In a geographically confined area, the analysis of the discourse of
      child psychiatry actors and their partners and a review of the locally produced
      literature highlights a wide range of initiatives, experiences and experiments in
      the interstices of the care system, between prevention and care, ambulatory and
      hospital care, and therapy, education and schools. These factors have contributed
      to changing the local landscape of mental health by reorganizing the provision of
      care and prevention. However, they have yet to become the norm, and only some
      professional groups interested in becoming suitably qualified and keen to improve
      the treatment of adolescent mental health problems are currently involved.

PMID- 22370079
TI  - [Peer support in a patient organization in psychiatry. Experience and practices].
AB  - Mental health patient organizations have only recently found a place among mental
      health stakeholders. Their activities at an individual level are based on a range
      of activities involving peer support, including mutual help groups or MHGs
      (similar to consumer-run organizations). A qualitative study based on an
      ethnographic approach was conducted in a patient organization at the Centre
      Hospitalier Sainte-Anne, where volunteers working in patient organizations
      receive visitors. The study examines the experiences and practices of patient
      organization members acting as peer helpers in order to reflect on what patient
      organizations are able to contribute to people receiving psychiatric treatment.
      The results show that peer helpers in the patient organization or mutual help
      groups share the experience of recovery and promote peer support. These practices
      are in line with the demands of people with mental disorders expressed at
      different stages of their treatment. Four main components of the process of peer
      support were identified. This study shows the specificity of this kind of
      practice in relation to the current range of resources in mental health.

PMID- 22370080
TI  - [The implementation of integrated networks of mental health services in Quebec:
      context of introduction, state of implementation and the views of general
      practitioners].
AB  - This paper presents the emerging context of integrated service networks (ISN),
      clarifies the concept of ISN, and highlights some of the key factors in the
      successful implementation of ISNs. The Quebec healthcare reform illustrates the
      current state of development of integrated care. The main targets of the reform
      are the consolidation of primary care and the development of collaborative models
      of mental health care (or shared care). Since they are very complex to operate
      (insofar as they require major system changes), ISNs are not widely developed.
      General practitioners are at the heart of the current reforms since they have a
      key role to play in the successful implementation of integrated care models,
      including ISN models.

PMID- 22370081
TI  - [The role of school doctors in the diagnosis of pervasive developmental
      disorders].
AB  - This study examined children with significant socialization problems receiving
      community care but without a diagnosis. An investigation conducted among school
      doctors working in Seine-Saint-Denis (Paris, France) showed that 3.9 per 1000
      nursery school pupils (maternelle) and 0.2 per 1000 middle school pupils
      (college) suffered from a pervasive developmental disorder. Quantitative and
      qualitative data show the difficulty of obtaining a diagnosis and assessment that
      complies with the recommendations of the French National Authority for Health.
      The study showed that more than 50% of parents of children with a recognized
      disability had either not been informed of or not understood their child's
      diagnosis.

PMID- 22370082
TI  - [Medical-psychiatric units: shared care in mental health].
AB  - This paper describes a highly unusual hospital unit that combines somatic and
      psychiatric approaches under the generic heading of a Medico-Psycho-Social Unit
      (MPSU) established at Angers University Hospital since 1996. The paper examines
      the value of a mixed approach while highlighting its limitations. The interest of
      the MPSU is that it provides a multidisciplinary, somatic and psychiatric
      approach on the same site. The joint expertise of medical and paramedical staff
      is required in cases where the assessment of the consultation-liaison services is
      not sufficient and in complex situations requiring the resources of an intensive
      care unit and specific medical and surgical specialties. Based on an established
      partnership and joint service provision, this type of unit is relatively uncommon
      both in France and abroad. However, the prevalence of somatic and organic
      comorbidity suggests that MPSUs are an innovative solution for the challenges of
      this type of care. Two clinical cases will be used as examples.

PMID- 22370083
TI  - [Legal empowerment and mental health: the legal subject in hospitals].
AB  - A social experiment and pilot project funded by the French Directorate General of
      Social Cohesion aimed at providing legal aid services ("legal empowerment and
      mental health") has been conducted since 2009 in three healthcare institutions in
      Paris (France): the Centre Hospitalier Sainte-Anne, the Groupe Public de Sante
      Perray-Vaucluse, and the Hopital Tenon (psychotraumatology unit). Lasting until
      2012 and piloted by the NGO Droits d'Urgence, the initiative aims to promote the
      legal empowerment of socially excluded people suffering from psychiatric or
      mental disorders and to facilitate access to care. The initiative operates on two
      levels, providing legal support to vulnerable people and offering legal expertise
      and advice to medical and social staff. An ad-hoc intervention approach was
      designed to ensure the implementation of the initiative based on several combined
      tools: legal aid, technical committees, awareness-raising activities, and pooling
      of legal resources and information. Developed across the three institutions, this
      integrated and subsidiary initiative improves our understanding of the complex
      circumstances of disempowered people ? who are often faced with overlapping
      social, medical, administrative and legal difficulties ? and helps to take into
      account their vulnerabilities. The cross-professional and cross-boundary system
      promoted by this initiative involves medical staff, social workers and lawyers
      around patients viewed as both actors and legal subjects.

PMID- 22370084
TI  - [Prevention and child mental health: the ethical issues raised by targeted
      approaches].
AB  - The details of the implementation of early prevention in child mental health in
      France have been at the heart of a debate between the defenders of a universal
      approach and the proponents of an approach targeting specific populations. The
      universal approach draws on various aspects of mother and child care and early
      childhood care offering considerate and expressive prevention based on a
      relationship of trust developed over time between professionals, parents and
      children. The targeted approach is based on the development of programs aimed at
      identifying vulnerable or at-risk populations. The ethical issues raised by
      targeted strategies are presented and discussed. The study highlights the
      difficulty of distinguishing between the social, educational, medical and
      psychological issues raised by early prevention.

PMID- 22370085
TI  - [The links between justice and public health: a major issue for psychiatry and
      the public authorities].
AB  - The level of cooperation between legal and healthcare professionals in psychiatry
      has increased significantly as a result of the greater emphasis on safety and
      security and the increasing tendency to place mental disorders in a judicial or
      legal context. As a result of the many new laws that have been passed since 1998,
      psychiatrists are increasingly required "to treat criminal recidivism and prevent
      violent behavior". These issues have been highlighted by the scientific, medical
      and legal community, though without ever resulting in any action by the public
      authorities. Based on an examination of the care provided to a prisoner before,
      during and after incarceration, this study suggests that despite the existing
      regulatory framework and the abundance of data on the provision of care
      (including psychiatric care), a comprehensive review of the current system is
      required. To what extent is care management effective and consistent? Are the
      stated economic objectives achievable? This paper argues that in a prison context
      the range of healthcare options needs to be clearly defined and laid out in order
      to provide mental health patients and mental health professionals with a
      realistic vision of care provision.

PMID- 22370087
TI  - Association between residential proximity to fuel-fired power plants and
      hospitalization rate for respiratory diseases.
AB  - BACKGROUND: Air pollution is known to cause respiratory disease. Unlike motor
      vehicle sources, fuel-fired power plants are stationary. OBJECTIVE: Using
      hospitalization data, we examined whether living near a fuel-fired power plant
      increases the likelihood of hospitalization for respiratory disease. METHODS:
      Rates of hospitalization for asthma, acute respiratory infection (ARI), and
      chronic obstructive pulmonary disease (COPD) were estimated using hospitalization
      data for 1993-2008 from New York State in relation to data for residences near
      fuel-fired power plants. We also explored data for residential proximity to
      hazardous waste sites. RESULTS: After adjusting for age, sex, race, median
      household income, and rural/urban residence, there were significant 11%, 15%, and
      17% increases in estimated rates of hospitalization for asthma, ARI, and COPD,
      respectively, among individuals > 10 years of age living in a ZIP code containing
      a fuel-fired power plant compared with one that had no power plant. Living in a
      ZIP code with a fuel-fired power plant was not significantly associated with
      hospitalization for asthma or ARI among children < 10 years of age. Living in a
      ZIP code with a hazardous waste site was associated with hospitalization for all
      outcomes in both age groups, and joint effect estimates were approximately
      additive for living in a ZIP code that contained a fuel-fired power plant and a
      hazardous waste site. CONCLUSIONS: Our results are consistent with the hypothesis
      that exposure to air pollution from fuel-fired power plants and volatile
      compounds coming from hazardous waste sites increases the risk of hospitalization
      for respiratory diseases.

PMID- 22370088
TI  - Imaging microcircuit function in healthy and diseased brain.
AB  - Neural microcircuits are the computational units of the mammalian brain. Recent
      evidence suggests that they are not composed exclusively of neurons but also
      involve other cell types such as astrocytes and microglia. In the healthy brain
      microglia, the resident immune cell, closely interacts with synapses and is
      likely to be involved in their structural plasticity. The interaction between the
      nervous and the immune systems is even more prominent under pathological
      conditions such as brain injury, inflammation and neurodegenerative diseases.
      This review discusses the techniques for high resolution imaging of microcircuit
      function in health and disease by focusing on some of the most recent advances in
      the field of in vivo calcium imaging of neurons, astrocytes and microglia.

PMID- 22370089
TI  - Low-level mercury exposure and peripheral nerve function.
AB  - BACKGROUND: Mercury is known to be neurotoxic at high levels. There have been few
      studies of potential peripheral neurotoxicity among persons with exposure to
      elemental mercury at or near background levels. OBJECTIVES: The present study
      sought to examine the association between urinary mercury concentration and
      peripheral nerve function as assessed by sensory nerve conduction studies in a
      large group of dental professionals. METHODS: From 1997 through 2006 urine
      mercury measurements and sensory nerve conduction of the median and ulnar nerves
      in the dominant hand were performed, and questionnaires were completed, on the
      same day in a convenience sample of dental professionals who attended annual
      conventions of the American Dental Association. Linear regression models,
      including repeated measures models, were used to assess the association of urine
      mercury with measured nerve function. RESULTS: 3594 observations from 2656
      subjects were available for analyses. Urine mercury levels in our study
      population were higher than, but substantially overlap with, the general
      population. The only stable significant positive association involved median (not
      ulnar) sensory peak latency, and only for the model that was based on initial
      observations and exclusion of subjects with imputed BMI. The present study found
      no significant association between median or ulnar amplitudes and urine mercury
      concentration. CONCLUSIONS: At levels of urine mercury that overlap with the
      general population we found no consistent effect of urine mercury concentration
      on objectively measured sensory nerve function.

PMID- 22370090
TI  - ER chaperone-metal interactions: links to protein folding disorders.
AB  - Chaperones in the endoplasmic reticulum play vital roles in the folding,
      assembly, and post-translational modification of secretory proteins and also
      recycle, refold, or initiate degradation of misfolded proteins. Chaperone
      deficiencies in either amount or function are implicated in the etiology or
      pathogenesis of Alzheimer's disease and other protein folding disorders of the
      central nervous system. In this review, we discuss evidence that chaperones
      become pathologic through deleterious interactions with metals and then promote
      protein folding disorders. The "master regulator" chaperone GRP78 in the
      endoplasmic reticulum is a compelling subject for investigation in this context
      because it is located at the hub of signaling pathways in a complex chaperone
      network. It has therefore been studied by several laboratories in conjunction
      with exposure to toxic metals. The key points of this review are that metals are
      implicated in the etiology or pathogenesis of Alzheimer's disease and other
      protein folding disorders, metals induce the expression GRP78, often associated
      with oxidative stress, some metals bind to GRP78, and lead (Pb) impairs GRP78
      function when it binds to GRP78. If certain metals do indeed cause or promote the
      aggregation of toxic proteins in the central nervous system, as the available
      evidence indicates, the identification of the mechanisms by which they act would
      provide valuable leads for the development of therapies to prevent or reverse
      toxic protein aggregation.

PMID- 22370091
TI  - Endogenous mitochondrial oxidative stress in MnSOD-deficient mouse embryonic
      fibroblasts promotes mitochondrial DNA glycation.
AB  - The accumulation of somatic mutations in mitochondrial DNA (mtDNA) induced by
      reactive oxygen species (ROS) is regarded as a major contributor to aging and age
      related degenerative diseases. ROS have also been shown to facilitate the
      formation of certain advanced glycation end-products (AGEs) in proteins and DNA
      and N(2)-carboxyethyl-2'-deoxyguanosine (CEdG) has been identified as a major DNA
      bound AGE. Therefore, the influence of mitochondrial ROS on the glycation of
      mtDNA was investigated in primary embryonic fibroblasts derived from mutant mice
      (Sod2(-/+)) deficient in the mitochondrial antioxidant enzyme manganese
      superoxide dismutase. In Sod2(-/+) fibroblasts vs wild-type fibroblasts, the CEdG
      content of mtDNA was increased from 1.90 +/- 1.39 to 17.14 +/- 6.60 pg/MUg DNA
      (p<0.001). On the other hand, the CEdG content of nuclear DNA did not differ
      between Sod2(+/+) and Sod2(-/+) cells. Similarly, cytosolic proteins did not show
      any difference in advanced glycation end-products or protein carbonyl contents
      between Sod2(+/+) and Sod2(-/+). Taken together, the data suggest that
      mitochondrial oxidative stress specifically promotes glycation of mtDNA and does
      not affect nuclear DNA or cytosolic proteins. Because DNA glycation can change
      DNA integrity and gene functions, glycation of mtDNA may play an important role
      in the decline of mitochondrial functions.

PMID- 22370092
TI  - Oxidant signaling for interleukin-13 gene expression in lung smooth muscle cells.
AB  - The growth of airway and vascular smooth muscle cells occurs in various lung
      diseases including asthma, chronic obstructive pulmonary disease,
      bronchopulmonary dysplasia, lymphangioleiomyomatosis, and pulmonary hypertension.
      Although inflammatory responses are critical in these diseases, the relationship
      between smooth muscle cell growth and inflammatory mediators is poorly
      understood. This study demonstrates that platelet-derived growth factor (PDGF)
      promotes the expression of interleukin-13 (IL-13) in lung smooth muscle cells
      through an oxidant signaling mechanism. Treatment of cultured human airway or
      pulmonary vascular smooth muscle cells with PDGF promotes IL-13 mRNA and protein
      expression. IL-13 expression is also detected in smooth muscle of airways and
      pulmonary vessels in allergen-stimulated mice. PDGF activates the proximal 980-bp
      region of the IL-13 promoter. PDGF-induced IL-13 expression is suppressed by the
      inhibition of reactive oxygen species signaling such as by NAD(P)H oxidase
      inhibition, reactive oxygen species scavenging, and metal chelation. Treatment of
      cells with hydrogen peroxide at as low as 1 MUM also promotes IL-13 gene
      expression. PDGF-induced cell growth is suppressed by the neutralizing antibody
      against IL-13 as well as by reactive oxygen inhibitors, and recombinant IL-13
      promotes the growth of airway smooth muscle cells. These results demonstrate that
      oxidant signaling activates IL-13 gene transcription in lung smooth muscle cells
      and that this signaling mechanism regulates cell growth.

PMID- 22370093
TI  - Nrf2 deficiency in myeloid cells is not sufficient to protect mice from high-fat
      diet-induced adipose tissue inflammation and insulin resistance.
AB  - Activation of the transcription factor NF-E2-related factor 2 (Nrf2) by oxidative
      stress induces the expression of a variety of antioxidant and anti-inflammatory
      genes. Yet, genetic ablation of Nrf2 was shown to protect mice from high-fat diet
      (HFD)-induced obesity and insulin resistance. The mechanisms that underlie this
      seemingly paradoxical finding remain largely unexplored. Here we examined whether
      Nrf2 deficiency in myeloid cells contributes to protection against HFD-induced
      metabolic changes by decreasing adipose tissue inflammation. In vitro, induction
      of IL-1beta by inflammatory stimuli was significantly reduced in Nrf2-deficient
      macrophages. Whereas inflammatory gene expression in the stromal vascular
      fraction was reduced in both global and chimeric Nrf2 KO mice, only global Nrf2
      deficient, and not bone marrow-transplanted Nrf2 chimeric, mice were protected
      against HFD-induced adipose tissue inflammation. Whereas global Nrf2 deficiency
      resulted in significantly decreased expression of inflammatory genes and
      PPARgamma2, there was no difference when Nrf2 was absent only from myeloid cells.
      In vitro coculture with adipocytes demonstrated that macrophage Nrf2 regulated
      inflammatory gene expression in macrophages; however, it was not required to
      induce inflammatory gene expression in adipocytes. Finally, in contrast to global
      Nrf2 knockout, Nrf2 deficiency in myeloid cells did not protect against HFD
      induced insulin resistance. Together, our data demonstrate a dominant role for
      nonmyeloid Nrf2 in controlling HFD-induced adipose tissue inflammation and the
      development of insulin resistance.

PMID- 22370094
TI  - Theoretical study on the inverse modeling of deep body temperature measurement.
AB  - We evaluated the theoretical aspects of monitoring the deep body temperature
      distribution with the inverse modeling method. A two-dimensional model was built
      based on anatomical structure to simulate the human abdomen. By integrating
      biophysical and physiological information, the deep body temperature distribution
      was estimated from cutaneous surface temperature measurements using an inverse
      quasilinear method. Simulations were conducted with and without the heat effect
      of blood perfusion in the muscle and skin layers. The results of the simulations
      showed consistently that the noise characteristics and arrangement of the
      temperature sensors were the major factors affecting the accuracy of the inverse
      solution. With temperature sensors of 0.05  degrees C systematic error and an
      optimized 16-sensor arrangement, the inverse method could estimate the deep body
      temperature distribution with an average absolute error of less than 0.20 
      degrees C. The results of this theoretical study suggest that it is possible to
      reconstruct the deep body temperature distribution with the inverse method and
      that this approach merits further investigation.

PMID- 22370095
TI  - Facial emotion recognition in adolescents with psychotic-like experiences: a
      school-based sample from the general population.
AB  - BACKGROUND: Psychotic symptoms, also termed psychotic-like experiences (PLEs) in
      the absence of psychotic disorder, are common in adolescents and are associated
      with increased risk of schizophrenia-spectrum illness in adulthood. At the same
      time, schizophrenia is associated with deficits in social cognition, with
      deficits particularly documented in facial emotion recognition (FER). However,
      little is known about the relationship between PLEs and FER abilities, with only
      one previous prospective study examining the association between these abilities
      in childhood and reported PLEs in adolescence. The current study was a cross
      sectional investigation of the association between PLEs and FER in a sample of
      Irish adolescents. METHOD: The Adolescent Psychotic-Like Symptom Screener (APSS),
      a self-report measure of PLEs, and the Penn Emotion Recognition-40 Test (Penn ER
      40), a measure of facial emotion recognition, were completed by 793 children aged
      10-13 years. RESULTS: Children who reported PLEs performed significantly more
      poorly on FER (beta=-0.03, p=0.035). Recognition of sad faces was the major
      driver of effects, with children performing particularly poorly when identifying
      this expression (beta=-0.08, p=0.032). CONCLUSIONS: The current findings show
      that PLEs are associated with poorer FER. Further work is needed to elucidate
      causal relationships with implications for the design of future interventions for
      those at risk of developing psychosis.

PMID- 22370096
TI  - Surface nucleation and growth in the system of interacting particles.
AB  - Recent experiments on epitaxial growth of metals on graphene have shown a strong
      dependence of island densities on coverage. These investigations cannot be
      explained by the standard mean-field nucleation theories. To understand them, we
      extend to higher coverage the former theory of rate equations developed for the
      initial state of nucleation, in a system where adsorbate interaction is included.
      We account for that, in the case of high coverage, the repulsive interaction
      influences both the attachment of monomers to clusters and the mobility of atoms.
      In our work we analyze the modification of the dependence of the island density
      on coverage, temperature and F/D ratio. In some regimes our theory results in the
      experimentally observed substantial growth of island density with coverage for a
      high deposited amount and a weak dependence on deposition rate F. We also find
      out the local maxima in temperature dependence of island density, as a
      consequence of long-range repulsive interactions.

PMID- 22370097
TI  - Prediction of the attenuation of the ascending aorta using bolus-tracking
      parameters and heart rate in coronary computed tomography angiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the correlation between
      bolus-tracking parameters and heart rate (HR) with attenuation of the ascending
      aorta and create a linear regression model for predicting coronary attenuation in
      coronary computed tomography angiography (CCTA). METHODS: A total of 50 patients
      (31 men, 19 women; mean age, 67.2+/-10.8 y) underwent CCTA using a 320-detector
      CT scanner. A bolus-tracking scan was performed to optimize the scan timing. The
      average HR under normal breathing for 10s was recorded just before the bolus
      tracking scan started. Attenuation values of the pulmonary artery at 7s (PA7) and
      10s (PA10) after the beginning of the injection were recorded during the bolus
      tracking scan and the ascending aortic attenuation (CEAAo) was measured during
      the diagnostic scan. RESULTS: A positive correlation was observed between PA7 and
      CEAAo (r=0.41, P=0.003) and PA10 and CEAAo (r=0.66, P<0.0001), and weak negative
      correlation was observed between HR and CEAAo (r=-0.46, P=0.15). A multivariable
      linear regression model for predicting CEAAo was evaluated, and the residual
      error between the predicted and the measured CEAAo was within approximately +/
      100 HU. CONCLUSIONS: Coronary attenuation could be predicted using HR and
      pulmonary artery attenuation during the bolus-tracking method.

PMID- 22370098
TI  - Phytotoxicity induced in isolated zooxanthellae by herbicides extracted from
      Great Barrier Reef flood waters.
AB  - To date there has been limited evidence anthropogenically sourced pollution from
      catchments reaching corals of the Great Barrier Reef (GBR). In this study,
      freshly isolated zooxanthellae were exposed to polar chemicals (chiefly
      herbicides) extracted from water samples collected in a flood plume in the GBR
      lagoon. Photosynthetic potential of the isolated zooxanthellae declined after
      exposure to concentrated extracts (10 times) from all but one of the sampling
      sites. Photosynthetic potential demonstrated a significant positive relationship
      with the concentration of diuron in the concentrated extracts and a significant
      inverse relationship with salinity measured at the sampling site. This study
      demonstrates that runoff from land based application of herbicides may reduce
      photosynthetic efficiency in corals of inshore reefs in the GBR. The ecological
      impacts of the chemicals in combination with other potential stressors on corals
      remain unclear.

PMID- 22370100
TI  - Single-stranded DNAzyme-based Pb2+ fluorescent sensor that can work well over a
      wide temperature range.
AB  - DNAzymes have become an excellent choice for sensing applications. Based on
      DNAzymes, three generations of Pb(2+) fluorescent sensors have been reported. In
      these sensors, two oligonucleotide strands (substrate strand and enzyme strand)
      were used, which not only increased the complexity of the detection system, but
      also brought some difficulties for the use of the sensors at elevated
      temperatures. To overcome this problem, a single-stranded DNAzyme-based Pb(2+)
      fluorescent sensor was designed by combining the substrate sequence and the
      enzyme sequence into one oligonucleotide strand. The intramolecular duplex
      structure of this single-stranded DNAzyme kept the fluorophore and the quencher,
      labeled at its two ends, in close proximity; thus the background fluorescence was
      significantly suppressed. Using this fluorescent sensor, Pb(2+) quantitation can
      be achieved with high sensitivity and high selectivity. In addition, the
      extraordinary stability of the intramolecular duplex structure could assure a low
      background fluorescence at high temperature, even if the number of complementary
      base pairs between the substrate sequence and the enzyme sequence was reduced,
      allowing the sensor to work well over a wide temperature range. Similar
      performances of the fluorescent sensor at 4, 25 and 37 degrees C suggested that
      this sensor has a good ability to resist temperature fluctuations.

PMID- 22370101
TI  - The predominance of Th17 lymphocytes and decreased number and function of Treg
      cells in preeclampsia.
AB  - The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T
      lymphocytes producing IL-17, IL-2, IFN-gamma, and IL-4, plus
      CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients
      with preeclampsia and healthy women in the third trimester of normal pregnancy.
      Another purpose was to assess the immunosuppressive activity of Treg cells from
      patients with preeclampsia compared with controls. Thirty-four preeclampsia
      patients and 27 healthy pregnant women were included. The percentages of
      CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with
      intracellular expressions of cytokines were estimated using monoclonal antibodies
      and flow cytometry. In vitro functional assays were performed using a Treg Cell
      Isolation Kit and (3)H-thymidine incorporation assays. The percentage of
      CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in
      preeclampsia than in healthy, normotensive pregnant women in the third trimester
      (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly
      lower in the study group compared with controls (p<0.05). There was no change in
      the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia
      patients without Treg cells and after addition of autologous Treg cells. In
      normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was
      significantly higher without Treg cells compared with the response after addition
      of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17
      immune response in preeclampsia. The decreased number and function of Treg cells
      may be responsible for activating the inflammatory response characteristic of
      this disorder. In preeclampsia, the predominance of Th17 immunity could act
      through modulating the Th1/Th2 immune balance.

PMID- 22370102
TI  - Impact of age on leptin and adiponectin independent of adiposity.
AB  - Age-related changes in leptin and adiponectin levels remain controversial, being
      affected by inconsistent normalisation for adiposity and body fat distribution in
      the literature. In a cross-sectional study on 210 Caucasians (127 women, eighty
      three men, 18-78 years, BMI 16.8-46.8 kg/m2), we investigated the effect of age
      on adipokine levels independent of fat mass (FM measured by densitometry),
      visceral and subcutaneous adipose tissue volumes (VAT and SAT assessed by whole
      body MRI). Adiponectin levels increased with age in both sexes, whereas leptin
      levels decreased with age in women only. There was an age-related increase in VAT
      (as a percentage of total adipose tissue, VAT%TAT), associated with a decrease in
      SAT(legs)%TAT. Adiposity was the main predictor of leptin levels, with 75.1 % of
      the variance explained by %FM in women and 76.6 % in men. Independent of
      adiposity, age had a minor contribution to the variance in leptin levels (5.2 %
      in women only). The variance in adiponectin levels explained by age was 14.1 % in
      women and 5.1 % in men. In addition, independent and inverse contributions to the
      variance in adiponectin levels were found for truncal SAT (explaining additional
      3.0 % in women and 9.1 % in men) and VAT%TAT (explaining additional 13.0 % in
      men). In conclusion, age-related changes in leptin and adiponectin levels are
      opposite to each other and partly independent of adiposity and body fat
      distribution. Normalisation for adiposity but not for body fat distribution is
      required for leptin. Adiponectin levels are adversely affected by subcutaneous
      and visceral trunk fat.

PMID- 22370103
TI  - Progesterone for preterm birth prevention.
AB  - Preterm birth-delivery before 37 weeks of gestation-is the second leading cause
      of infant mortality in the United States after congenital malformations.
      Spontaneous preterm birth, due to either preterm labor or preterm premature
      membrane rupture, encompasses approximately 75% of all preterm births, almost
      400,000 births per year. Since the 1960s, different formulations of progesterone
      have been investigated for preterm birth prevention. This article addresses the
      use of progesterone for the prevention of preterm birth, including selection of
      candidates for progesterone, pharmacokinetics, dosing, and formulations. This
      article aims to provide a practical guide for using progesterone in clinical
      practice.

PMID- 22370104
TI  - Periodontal disease and preterm birth.
AB  - Preterm birth (delivery at fewer than 37 weeks' gestation) is the most common
      cause of infant morbidity and mortality among nonanomalous infants in the United
      States. Increasing evidence has focused on associations between clinical
      infection, inflammation, and preterm birth. Maternal periodontal disease, which
      is associated with systemic inflammation, has been associated with preterm birth.
      Intervention trails for treatment of periodontal disease during pregnancy,
      however have not consistently shown a reduction in preterm birth rates. Despite
      the lack of reduction in preterm birth, oral health maintenance is an important
      part of preventive care and should be supported during pregnancy.

PMID- 22370105
TI  - Cervical cerclage for the prevention of preterm birth.
AB  - Contemporary evidence supports the concept that cervical insufficiency is
      anything but a well-defined and distinct clinical entity. Instead, it is only 1
      component of the larger and more complex preterm birth syndrome. Premature
      cervical ripening, as evidenced by shortening and effacement beginning at the
      internal os, provides strong evidence that parturition has begun and is the
      result of multiple interrelated pathways and inciting factors. Ultrasonographic
      screening of the cervix and treatment with cerclage for cervical shortening in
      the mid-trimester is reserved for women with prior spontaneous preterm birth
      (Fig. 1). Although cerclage benefit increases as the cervix shortens to less than
      25 mm, it is appropriate to offer cerclage to women with shortened cervical
      length of less than 25 mm, and particularly those with a coexistent U-shaped
      funnel.

PMID- 22370106
TI  - Late preterm birth: management dilemmas.
AB  - In summary, late preterm birth results from spontaneous, indicated, and sometime
      elective indications. The burden of prematurity can be decreased if elective late
      preterm delivery is eliminated. While recent recommendations from the NICHD/SMFM
      workshop on timing of late preterm and early term birth have helped to guide
      management, the authors acknowledge that most of their guidelines are based on
      grade B or C evidence. Certain conditions absolutely warrant late preterm
      delivery; however, the clinician should weigh the risks of iatrogenic prematurity
      with the benefits of delivery for maternal or fetal indication when considering
      intervention for this cohort.

PMID- 22370108
TI  - Antibiotics in the management of PROM and preterm labor.
AB  - A significant fraction of preterm birth results from subclinical intrauterine
      infection. It is presumed that ascending bacterial colonization of the decidua
      results and either uterine contractions or membrane weakening that results in the
      clinical presentation of preterm labor or PROM. Those with overt infection
      require delivery. However, it is plausible that adjunctive antibiotic treatment
      during therapy for preterm labor and PROM remote from term could result in
      pregnancy prolongation and reductions in gestational age-dependent and infectious
      newborn morbidities. Data support adjunctive antibiotic treatment during
      conservative management of PROM remote from term. Such treatment should include
      broad-spectrum agents, typically intravenous therapy initially, and continue for
      up to 7 days if undelivered. Such treatment should be reserved for women
      presenting remote from term where significant improvement in neonatal outcomes
      can be anticipated with conservative management. Alternatively, current evidence
      suggests that antibiotic treatment in the setting of preterm labor with intact
      membranes does not consistently prolong pregnancy or improve newborn outcomes.
      Given this, and the concerning findings from the ORACLE II trial of antibiotics
      for preterm labor, this treatment should not be offered in the setting of preterm
      labor with intact membranes. Although one could speculate that women with preterm
      labor and with either a short cervical length for a positive fetal fibronectin
      screen might benefit from antibiotic therapy, no well-designed, randomized,
      controlled trials addressing this issue have been completed. Therefore,
      antibiotic therapy for women in preterm labor should be reserved for usual
      clinical indications, including suspected bacterial infections, GBS prophylaxis,
      and chorioamnionitis.

PMID- 22370107
TI  - Antenatal corticosteroids in the management of preterm birth: are we back where
      we started?
AB  - Though the preterm birth rate in the United States has finally begun to decline,
      preterm birth remains a critical public health problem. The administration of
      antenatal corticosteroids to improve outcomes after preterm birth is one of the
      most important interventions in obstetrics. This article summarizes the evidence
      for antenatal corticosteroid efficacy and safety that has accumulated since
      Graham Liggins and Ross Howie first introduced this therapy. Although antenatal
      corticosteroids have proven effective for singleton pregnancies at risk for
      preterm birth between 26 and 34 weeks' gestation, questions remain about the
      utility in specific patient populations such as multiple gestations, very early
      preterm gestations, and pregnancies complicated by IUGR. In addition, there is
      still uncertainty about the length of corticosteroid effectiveness and the need
      for repeat or rescue courses. Though a significant amount of data has accumulated
      on antenatal corticosteroids over the past 40 years, more information is still
      needed to refine the use of this therapy and improve outcomes for these at-risk
      patients.

PMID- 22370109
TI  - Tocolytic therapy for acute preterm labor.
AB  - The pathophysiology leading to preterm labor is not well understood and often
      multifactorial; initiating factors include intrauterine infection, inflammation,
      ischemia, overdistension, and hemorrhage. Given these different potential causes,
      directing therapy for preterm labor has been difficult and suboptimal. To date,
      no single drug has been identified as successful in treating all of the
      underlying mechanisms leading to preterm labor. In addition, the methodology of
      many of the tocolytic studies is limited by lack of sufficient patient numbers,
      lack of comparison with a placebo, and inconsistent use of glucocorticoids. The
      limitations in these individual studies make it difficult to evaluate the
      efficacy of a single tocolytic by meta-analysis. Despite these limitations, the
      goals for tocolysis for preterm labor are clear: To complete a course of
      glucocorticoids and secure the appropriate level of neonatal care for the fetus
      in the event of preterm delivery. The literature demonstrates that many tocolytic
      agents inhibit uterine contractility. The decision as to which tocolytic agent
      should be used as first-line therapy for a patient is based on multiple factors,
      including gestational age, the patient's medical history, common and severe side
      effects, and a patient's response to therapy. In a patient at less than 32 weeks
      gestation, indomethacin may be a reasonable first choice based on its efficacy,
      ease of administration, and minimal side effects. Concurrent administration of
      magnesium for neuroprotection may be given. At 32 to 34 weeks, nifedipine may be
      a reasonable first choice because it does not carry the fetal risks of
      indomethacin at these later gestational ages, is easy to administer, and has
      limited side effects relative to beta-mimetics. In an effort to review a commonly
      faced obstetrical complication, this article has provided a summary of the most
      commonly used tocolytics, their mechanisms of action, side effects, and clinical
      data regarding their efficacy.

PMID- 22370110
TI  - Early term births: considerations in management.
AB  - The frequency of early term birth varies depending on patient, provider, and
      system characteristics. Early term deliveries are associated with suboptimal
      neonatal outcomes without evidence of maternal benefit. Some early term births
      are either unavoidable or absolutely indicated for maternal and/or fetal benefit
      in the setting of medical or obstetric risks. Demonstrated fetal lung maturity
      before early term birth reduces the risk of respiratory and other morbidities
      relative to gestational age-matched counterparts but may not reduce the risks to
      the low levels at 39 to 40 weeks. For some risk situations, it remains
      controversial whether earlier delivery is beneficial. The assessment of the
      provider and patient's desires should direct care. In the absence of any
      obstetric or medical risks, early term delivery should be avoided. A simple
      intervention that includes administrative support, review of indications, and
      feedback to providers can dramatically reduce the frequency of early term births
      over time.

PMID- 22370111
TI  - Management of preterm birth: best practices in prediction, prevention, and
      treatment.

PMID- 22370112
TI  - Management of preterm birth: best practices in prediction, prevention, and
      treatment. Preface.

PMID- 22370113
TI  - Evaluation of regional work from ECG-gated SPECT images through solution of
      equations of continuity for fluids-mechanical cardiac work calculated using thin
      wall model.
AB  - Regional contraction work (RCW) of left ventricle (LV) was evaluated from cardiac
      perfusion images of ECG-gated single photon emission computed tomography (ECG
      SPECT). The mechanical work was computed as a product of force and displaced
      distance. Force was determined from Laplace's law under a rectangle pressure.
      Deformation of wireframe representing LV was calculated from equations of
      continuity for two-dimensional fluids. Experiments were performed with homemade
      life-sized cardiac models. Total contraction work (TCW) and stroke work (SW) were
      524.0 +/- 166.1 mJ/beat and 709.8 +/- 169.5 mJ/beat, respectively, in normal
      subjects (n = 23). Moderate correlation was seen between TCW and SW (y = -43.4 +
      0.779 x, r = 0.815). The regional contraction amplitude (RCA), synchronous
      contraction index and RCW were 35.4 +/- 3.5%, 95.4 +/- 3.1% and 5.58 +/- 0.97 mJ
      cm(-2)/beat in normal subjects, whereas those in patients with decreased ejection
      raction (EF) <= 30% (n = 6) were 19.6 +/- 7.7%, 64.4 +/- 32.2% and 2.58 +/- 0.82
      mJ cm(-2)/beat (p < 0.0001, Student's t-test). There was a poor correlation
      between RCW and RCA (y = 1.648 +/- 0.116 x, r = 0.501) in normal subjects,
      suggesting that it might not be suitable to use RCA as an alternative to evaluate
      RCW.

PMID- 22370114
TI  - Aflatoxin exposure may contribute to chronic hepatomegaly in Kenyan school
      children.
AB  - BACKGROUND: Presentation with a firm type of chronic hepatomegaly of
      multifactorial etiology is common among school-age children in sub-Saharan
      Africa. OBJECTIVE: Aflatoxin is a liver toxin and carcinogen contaminating staple
      maize food. In this study we examined its role in chronic hepatomegaly. METHODS:
      Plasma samples collected in 2002 and again in 2004 from 218 children attending
      two schools in neighboring villages were assayed for aflatoxin exposure using the
      aflatoxin-albumin adduct (AF-alb) biomarker. Data were previously examined for
      associations among hepatomegaly, malaria, and schistosomiasis. RESULTS: AF-alb
      levels were high in children from both schools, but the geometric mean (95%
      confidence interval) in year 2002 was significantly higher in Matangini [206.5
      (175.5, 243.0) pg/mg albumin] than in Yumbuni [73.2 (61.6, 87.0) pg/mg; p <
      0.001]. AF-alb levels also were higher in children with firm hepatomegaly [176.6
      (129.6, 240.7) pg/mg] than in normal children [79.9 (49.6, 128.7) pg/mg; p =
      0.029]. After adjusting for Schistosoma mansoni and Plasmodium infection, we
      estimated a significant 43% increase in the prevalence of
      hepatomegaly/hepatosplenomegaly for every natural-log-unit increase in AF-alb. In
      2004, AF-alb levels were markedly higher than in 2002 [539.7 (463.3, 628.7) vs.
      114.5 (99.7, 131.4) pg/mg; p < 0.001] but with no significant difference between
      the villages or between hepatomegaly and normal groups [539.7 (436.7, 666.9) vs.
      512.6 (297.3, 883.8) pg/mg], possibly because acute exposures during an
      aflatoxicosis outbreak in 2004 may have masked any potential underlying
      relationship. CONCLUSIONS: Exposure to aflatoxin was associated with childhood
      chronic hepatomegaly in 2002. These preliminary data suggest an additional health
      risk that may be related to aflatoxin exposure in children, a hypothesis that
      merits further testing.

PMID- 22370115
TI  - Emotion regulation profiles in psychogenic non-epileptic seizures.
AB  - BACKGROUND: Psychogenic non-epileptic seizures (PNES) are frequently encountered
      in epilepsy referral centers, yet there is limited understanding of the emotion
      processing style in this psychiatrically heterogeneous population. Understanding
      profiles of emotion regulation in PNES will provide further evidence of the
      psychogenic nature of the disorder and will potentially inform psychotherapeutic
      interventions. METHODS: Fifty-five patients with PNES underwent a
      neuropsychiatric evaluation and completed self-report questionnaires that
      measured difficulties in emotion regulation, psychopathology severity and quality
      of life. RESULTS: Through the use of cluster analysis, two groups were
      identified; Cluster 1 represented a highly emotion dysregulated group while
      Cluster 2 represented a low emotion dysregulated group. Additional analyses
      revealed that each group significantly differed from normative data. Finally,
      Cluster 1 was significantly associated with several measures of psychiatric
      symptoms, higher rates of comorbid psychiatric diagnoses and impairment in
      quality of life. CONCLUSIONS: These findings suggest that patients with PNES may
      be subject to high levels of emotion dysregulation, severe psychiatric
      symptomatology and impaired quality of life, or to low emotion dysregulation
      characterized by emotional unawareness or avoidance. These profiles clearly
      differ from normative data regarding emotion regulation and their identification
      may help tailor psychotherapeutic interventions.

PMID- 22370117
TI  - Single tonic-clonic seizure after energy drink abuse.
AB  - Energy drinks are soft beverages especially marketed for adolescents in order to
      obtain a heightened sense of awareness. Concerns about the safety of these drinks
      are raised based on our observation of potentially serious adverse effects.
      Caffeine and taurine are psychoactive agents highly present in energy drinks,
      which may lead to modification of neurotransmission. We herein report the case of
      a 20-year-old man presenting with a generalized epileptic seizure after energy
      drink consumption.

PMID- 22370116
TI  - Rational polytherapy with lacosamide in clinical practice: results of a Spanish
      cohort analysis RELACOVA.
AB  - There has been little long-term success with polytherapy for patients with
      refractory partial-onset epilepsy. The rational combination of antiepileptic
      drugs based on their mechanism of action may help improve treatment efficacy and
      tolerability. Lacosamide, a novel sodium channel blocker (SCB), was investigated
      in 158 patients with partial-onset epilepsy in the prospective, multicenter,
      observational, RELACOVA cohort study conducted in Spain. After 12 months'
      treatment with lacosamide, 47% of patients were responders (>=50% reduction in
      seizure frequency) and 24% were seizure free. Lacosamide was well tolerated;
      dizziness was the most frequent adverse event. Efficacy was better (responder
      rate, 65% vs 38%; seizure free rate, 35% vs 17%) and there was a lower adverse
      event rate (33% vs 58%) in patients receiving non-SCBs (n=49) versus those
      receiving SCBs (n=104) as concomitant therapy at baseline. Further investigation
      of lacosamide combination therapy is warranted.

PMID- 22370118
TI  - Impact of the chronic use of benzodiazepines prescribed for seizure control on
      the anxiety levels of patients with epilepsy.
AB  - In a cross-sectional study, we evaluated the impact of the chronic use of
      benzodiazepines (BDZ) prescribed for seizure control on the anxiety levels of
      patients with temporal lobe epilepsy. We assessed the anxiety level of 99
      patients with temporal lobe epilepsy with (n=15) or without (n=84) BDZ for
      seizure control, using the Beck Anxiety Inventory (BAI) or the Hamilton Anxiety
      Scale (HAMA). Independent risk factors for high anxiety levels were being a
      female patient (O.R.=2.93; 95% C.I.=1.05-8.16; p=0.039), having uncontrolled
      seizures (O.R.=4.49; 95% C.I.=1.66-12.11; p=0.003) and having a history of a
      psychiatric disorder (O.R.=4.46; 95% C.I.=1.63-12.21; p=0.004). However, there
      were no statistically significant differences in anxiety levels between patients
      utilizing or not utilizing BDZ prescribed exclusively for seizure control. We
      concluded that in our study, patients with chronic use of BDZ prescribed
      exclusively for seizure control showed similar anxiety levels than patients who
      were not using this class of drug. Additional studies are needed to define better
      strategies for the treatment of anxiety disorders in epilepsy.

PMID- 22370119
TI  - Anatomically dependent anticonvulsant properties of temporally-coded electrical
      stimulation.
AB  - In the PTZ animal model of epilepsy, electrical stimulation applied to the
      amygdaloid complex may result in either pro-convulsive or anticonvulsant effect,
      depending on the temporal pattern used (i.e. periodic-PS and non-periodic-NPS
      electrical stimulation). Our hypothesis is that the anatomical target is a
      determinant factor for the differential effect of temporally-coded patterns on
      seizure outcome. The threshold dose of PTZ to elicit forelimb clonus and
      generalized tonic-clonic seizure behavior was measured. The effect of amygdaloid
      complex PS on forelimb clonus threshold showed a pro-convulsive effect while NPS
      was anticonvulsant. NPS also significantly increased generalized tonic-clonic
      threshold; while PS, although at lower threshold levels, did not present
      statistical significance. Thalamus stimulation did not affect forelimb clonus
      threshold and showed similar anticonvulsant profiles for both PS and NPS on
      generalized tonic-clonic threshold. In summary, the anatomical target is a
      determinant factor on whether temporally-coded ES differentially modulates
      seizure outcome.

PMID- 22370120
TI  - Prevalence of recurrent symptoms and their association with epilepsy and febrile
      seizure in school-aged children: a community-based survey in Iceland.
AB  - We determined the prevalence of common recurrent symptoms in a community-based
      study of children and investigated whether these symptoms were associated with
      epilepsy and febrile seizure. A questionnaire was developed and sent to parents
      of all children attending school in the Reykjavik school district, grades 1-10.
      The questions assessed personality traits, headache, epilepsy, febrile seizure,
      and recurrent symptoms. Of the 13,044 questionnaires distributed, 10,578 were
      returned (81%). We analyzed the subset of 9679 (91%) questionnaires with complete
      information on relevant factors. The prevalence of epilepsy was 7.7/1000; febrile
      seizures were reported in 5.1% of children. Prevalence estimates of recurrent
      symptoms were similar to the published literature. In our cohort, recurrent dizzy
      spells and recurrent visual disturbances were associated with epilepsy after
      adjustment for age, migraine and febrile seizure. This association could reflect,
      only in part, the occurrence of auras in children with epilepsy.

PMID- 22370121
TI  - Facile fabrication of organic-inorganic hybrid beads by aminated alginate enabled
      gelation and biomimetic mineralization.
AB  - Inspired by biomineralization, design and preparation of biomimetic organic
      inorganic composites have become a hot issue and a research frontier in many
      areas, including enzyme engineering. In this research, a unique and facile method
      for fabricating organic-inorganic hybrid beads is proposed. Modified alginate
      with a dual function of gelation and mineralization was synthesized for
      fabrication of hybrid carriers for enzyme immobilization. With the aid of EDC/NHS
      conjugation chemistry, the amine groups from diethylene triamine were grafted
      onto alginate in a controllable way. The resultant aminated alginate served
      manifold functions: forming a hydrogel via Ca(2+)-cross-linking, inducing the
      biomimetic silicification and manipulating the distribution of silica
      nanoparticles. Owing to the compact polymer network structure and the homogeneous
      silica nanoparticle dispersion, the as-prepared NH2-alginate/silica hybrid beads
      displayed superior swelling resistance and mechanical stability to pure alginate
      beads. The hybrid beads were subsequently utilized for encapsulation of yeast
      alcohol dehydrogenase (YADH). It was found that the thermal stability, pH
      tolerance and storage stability of the immobilized enzyme were all improved
      without significantly lowering the catalytic activity.

PMID- 22370122
TI  - Overcoming regulatory and economic challenges facing pharmacogenomics.
AB  - The number of personalized medicines and companion diagnostics in use in the
      United States has gradually increased over the past decade, from a handful of
      medicines and tests in 2001 to several dozen in 2011. However, the numbers have
      not reached the potential hoped for when the human genome project was completed
      in 2001. Significant clinical, regulatory, and economic barriers exist and
      persist. From a regulatory perspective, therapeutics and companion diagnostics
      are ideally developed simultaneously, with the clinical significance of the
      diagnostic established using data from the clinical development program of the
      corresponding therapeutic. Nevertheless, this is not (yet) happening. Most
      personalized medicines are personalized post hoc, that is, a companion diagnostic
      is developed separately and approved after the therapeutic. This is due in part
      to a separate and more complex regulatory process for diagnostics coupled with a
      lack of clear regulatory guidance. More importantly, payers have placed
      restrictions on reimbursement of personalized medicines and their companion
      diagnostics, given the lack of evidence on the clinical utility of many tests. To
      achieve increased clinical adoption of diagnostics and targeted therapies through
      more favorable reimbursement and incorporation in clinical practice guidelines,
      regulators will need to provide unambiguous guidance and manufacturers will need
      to bring more and better clinical evidence to the market place.

PMID- 22370123
TI  - Buckling instability of circular double-layered graphene sheets.
AB  - In this paper, we study the buckling properties of circular double-layered
      graphene sheets (DLGSs), using plate theory. The two graphene layers are modeled
      as two individual sheets whose interactions are determined by the Lennard-Jones
      potential of the carbon-carbon bond. An analytical solution of coupled governing
      equations is proposed for predicting the buckling properties of circular DLGSs.
      Using the present theoretical approach, the influences of boundary conditions,
      plate sizes, and buckling-mode shapes on the buckling behaviors are investigated
      in detail. The buckling stability is significantly affected by the buckling-mode
      shapes. As a result of van der Waals interactions, the buckling stress of
      circular DLGSs is much larger for the anti-phase mode than for the in-phase mode.

PMID- 22370124
TI  - Sodium selenite for treatment of Kashin-Beck disease in children: a systematic
      review of randomised controlled trials.
AB  - OBJECTIVE: To assess the effectiveness and safety of sodium selenite in treatment
      of patients with Kashin-Beck disease (KBD). METHODS: We searched for all
      publications between January 1966 and October 2011 using seven electronic
      databases. All randomized controlled trials (RCTs) assessing the effects of
      sodium selenite on KBD vs no treatment or placebo were included. For dichotomous
      data, odds ratios (OR) and 95% confidence intervals (CI) were estimated according
      to the intention-to-treat principles. For continuous data, mean difference (MD)
      was used for outcomes pooled on the same scale. RESULTS: A total of 10 RCTs
      involving 2244 patients were included. The methodological quality of the included
      studies was low. When comparing the outcome of sodium selenite treatment group vs
      the control group, the OR of repairing rate of metaphyseal lesions was 5.63 (95%
      CI: 3.67-8.63) and repairing rate at the distal end of phalanges was 2.98 (95%
      CI: 1.32-6.70) based on X-ray assessment, which was statistically significant
      difference in favour of sodium selenite. In one RCT which reported data on
      clinical improvement, no statistically significant difference was observed in the
      treatment vs control group (OR 1.50, 95% CI: 0.43-5.30). Se content in hair was
      (MD 0.11, 95% CI: 0.09-0.13) which was statistically significant higher in
      selenium group. CONCLUSIONS: Current evidence suggests that sodium selenite is
      more effective than placebo or no treatment in patients with KBD. However, the
      evidence was limited by potential biases; thus, further high quality large-scale
      RCTs are still needed to evaluate the short term and long term effects of
      selenium.

PMID- 22370125
TI  - Loop-mediated isothermal amplification (LAMP) assays for the detection of
      Theileria annulata infection in China targeting the 18S rRNA and ITS sequences.
AB  - We have developed two loop-mediated isothermal amplification (LAMP) assays for
      the detection of Theileria annulata, an economically important cattle disease in
      China that occurs in subtropical and tropical areas. These assays target the
      ribosomal RNA (18S rRNA) and ITS LAMP sequences. The primer set for each gene
      target consists of four primers, and each set recognizes six distinct regions on
      the target gene to allow for the highly specific detection of T. annulata. The
      specific ladder bands were amplified from the autologous genomic DNA of four
      Chinese-laboratory-preserved standard T. annulata stocks, and there were no cross
      reactions with the genomic DNA of normal bovine blood and other protozoan
      species. The LAMP assays were sufficiently sensitive to detect 0.1 pg/MUl of
      genomic DNA. Furthermore, DNA extracted from blood collected from cattle
      experimentally infected with T. annulata (18-105 days post-infection) was
      amplified, demonstrating the high sensitivity of these primers. Of the 351 field
      samples collected from China, 24.5% were positively detected by two LAMP primers,
      and 18.2% were found to be positive for T. annulata infection by PCR. These
      results indicate that the LAMP assay could be a potential diagnostic tool for
      epidemiological studies of T. annulata infection in China.

PMID- 22370126
TI  - Endemic Lagos bat virus infection in Eidolon helvum.
AB  - Phylogenetic analyses suggest lyssaviruses, including Rabies virus, originated
      from bats. However, the role of bats in the maintenance, transmission and
      evolution of lyssaviruses is poorly understood. A number of genetically diverse
      lyssaviruses are present in Africa, including Lagos bat virus (LBV). A high
      seroprevalence of antibodies against LBV was detected in Eidolon helvum bats.
      Longitudinal seroprevalence and age-specific seroprevalence data were analysed
      and capture-mark-recapture (CMR) analysis used to follow 98 bats over 18 months.
      These data demonstrate endemic infection, with evidence of horizontal
      transmission, and force of infection was estimated for differing age categories.
      The CMR analysis found survival probabilities of seronegative and seropositive
      bats were not significantly different. The lack of increased mortality in
      seropositive animals suggests infection is not causing disease after extended
      incubation. These key findings point towards acute transmission of bat
      lyssaviruses in adapted bat hosts that occurs at a far higher rate than the
      occurrence of disease.

PMID- 22370127
TI  - Salsolinol and isosalsolinol: condensation products of acetaldehyde and dopamine.
      Separation of their enantiomers in the presence of a large excess of dopamine.
AB  - Dopamine (DA) condenses, at least in vitro, with acetaldehyde, the primary
      metabolite of ethanol, to form the regioisomers salsolinol (SAL) and
      isosalsolinol (isoSAL). An alternative in vivo route to SAL, requiring a
      decarboxylation step, has been suggested via condensation of DA with pyruvic
      acid. SAL has been proposed as a mediator of the rewarding effects of ethanol in
      the brain. We have now shown by HPLC, nuclear magnetic resonance (NMR) and mass
      spectrometry (MS) that the commercially available SAL contains about 10% of
      isoSAL, whose biological activity is unknown. If SAL is indeed the biologically
      active metabolite, rather than isoSAL, it is also unknown whether the rewarding
      molecule is (S)- or (R)-SAL. We have developed methodologies for the quantitative
      determination of DA, SAL and isoSAL using ion-pair reversed-phase HPLC, and for
      the separation of DA from (S)- and (R)-SAL and an isoSAL enantiomer on a beta
      cyclodextrin-modified column, in both cases with electrochemical detection. A
      significant advance over earlier methods was achieved for the analysis of (S)-
      and (R)-SAL in the presence of a large excess of DA (100:1 DA-SAL ratio), as
      expected to occur in vivo, by suppressing the DA peak by selective derivatization
      with 2,3-naphthalenedicarboxaldehyde into a molecule that is electrochemically
      silent at the electrode potential used. The methodologies developed will allow
      the separation and determination of the pharmacological activity of these two
      products of condensation of acetaldehyde with DA. Further, the techniques for (S)
      and (R)-SAL separation at a high DA:SA ratio will allow the existence of a
      putative (R)-SAL synthase to be determined and, if it exists, its role in
      alcoholism.

PMID- 22370128
TI  - Variations of the superior sagittal sinus and bridging veins in human dissections
      and computed tomography venography.
AB  - OBJECTIVES: The aim of the present study was to examine the superior sagittal
      sinus (SSS) and bridging veins (BVs) from an anatomical, neurosurgical and
      radiological perspective. METHODS: Computed tomography venographies (CTVs) of 30
      patients and 9 cadaveric dissections of human SSS were analyzed. RESULTS: CTV and
      cadavers showed most BVs emptying into the SSS close by (+/-3 cm) and distal to
      the coronary suture (74% in CTV, 62% in cadavers). CONCLUSIONS: Important
      anatomical information can be drawn from cerebral CTV for neurosurgical
      preoperative planning.

PMID- 22370129
TI  - Correlation of apparent diffusion coefficients measured by diffusion-weighted MR
      imaging and standardized uptake values from FDG PET/CT in metastatic neck lymph
      nodes of head and neck squamous cell carcinomas.
AB  - Both diffusion-weighted magnetic resonance imaging and fluorodeoxyglucose
      positron emission tomography/computed tomography are oncological imaging
      techniques. The aim of this study was to assess any correlation between apparent
      diffusion coefficients and standardized uptake value in metastatic neck lymph
      nodes of head and neck squamous cell carcinomas.

PMID- 22370130
TI  - Diffusion-weighted magnetic resonance imaging of lung cancer at 3.0 T: a
      preliminary study on monitoring diffusion changes during chemoradiation therapy.
AB  - PURPOSE: The purpose of the study was to prospectively monitor changes of
      apparent diffusion coefficient (ADC) in perichemoradiation for lung cancer.
      METHODS: Fourteen patients with lung cancer who underwent chemoradiation therapy
      were included. Diffusion-weighted (DW) images were obtained prior to and during
      chemoradiation therapy, and ADCs were compared. RESULTS: Seven patients had
      qualified DW images before and during chemoradiation. Six responders had
      significant increase in ADC value during the chemoradiation compared with the
      pretreatment value (P=.028), while one nonresponder had a slight decrease.
      CONCLUSION: These preliminary results show the potential of DW imaging in
      monitoring early response to chemoradiation in patients with lung cancer.

PMID- 22370131
TI  - Small bowel tumors: spectrum of findings on 64-section CT enteroclysis with
      pathologic correlation.
AB  - Improvements in helical technology have made detection of benign and malignant
      small bowel tumors easier so that they are now frequently detected at an early
      stage. Sixty-four-section CT enteroclysis provides suggestive features that help
      determine the actual nature of a small bowel tumor in a large number of cases.
      Specific diagnosis of small bowel tumor is based on a combination of findings
      that are depicted owing to the use of the multiple capabilities of 64-section CT
      enteroclysis, allowing optimal planning prior to endoscopic or surgical
      resection.

PMID- 22370132
TI  - Colon cancer: comprehensive evaluation with 64-section CT colonography using
      water enema as intraluminal contrast agent-a pictorial review.
AB  - Sixty-four-section CT colonography with water enema combines intracolonic neutral
      contrast agent with high-resolution CT images of the abdomen. Owing to
      submillimeter isotropic voxels, high-quality reformatted images are obtained.
      High-resolution images offer added value for the detection and localization of
      colonic lesions, evaluation of the local extent of the disease, and depiction, if
      any, of synchronous colorectal lesions and distant metastases. Sixty-four-section
      CT colonography with water enema has a major role in the evaluation of patients
      with colon cancer before planning therapy. It can be used to complement failed or
      incomplete colonoscopy and investigate the colon in elderly patients.

PMID- 22370133
TI  - Portal biliopathy: imaging manifestations on multidetector computed tomography
      and magnetic resonance imaging.
AB  - Portal biliopathy refers to biliary abnormalities secondary to extrahepatic
      portal vein obstruction and cavernous transformation and is caused by vascular
      compression from peribiliary collateral vessels, producing segmental stenoses of
      the common bile duct and abnormal liver function test (LFT) results. A review of
      imaging studies yielded 18 patients with abnormal LFT results, biliary tract
      dilatation, and extrahepatic portal vein obstruction with cavernous
      transformation. Multidetector computed tomography and magnetic resonance imaging
      showed biliary stenotic segments in 11 patients secondary to extrinsic
      compression from enlarged peribiliary collaterals. Clinical and imaging follow-up
      demonstrated improvement in LFT results with minimal decrease in bile duct
      dilatation, eliminating percutaneous or endoscopic biliary intervention.

PMID- 22370134
TI  - The stiffness of the liver and spleen on ARFI Imaging pre and post TIPS
      placement: a preliminary observation.
AB  - PURPOSE: To prospectively assess the stiffness of the liver and spleen with
      acoustic radiation force impulse (ARFI) imaging pre and post transjugular
      intrahepatic portosystemic shunt (TIPS) placement. MATERIAL AND METHODS: Between
      February, 2011 and September, 2011, we prospectively measured stiffness of the
      liver and spleen with mean shear wave velocity (MSV, m/s) on ARFI imaging in 10
      healthy volunteers (mean age 32.2 +/- 10.3 years, age range 23-53 years) and 10
      patients (mean age, 38.6 +/- 6.4 years, age range 30-48 years) who underwent TIPS
      placement for treatment of portal hypertension (PHTN). The portal vein pressure
      was measured while placing the TIPS. To assess the changes in the stiffness of
      the liver and spleen following TIPS placement, we measured MSV of the liver and
      spleen one day before TIPS insertion and 4-9 days after TIPS placement (mean
      interval 5.9 +/- 2.0 days, interval range 5 to 10 days). RESULTS: There was
      significant difference in portal vein pressure pre (27.67 +/- 5.86 mmHg) and post
      (18.00 +/- 6.93 mmHg) TIPS insertion (P<.01). The MSV of the liver in healthy
      subjects, patients with PHTN pre TIPS and patients with PHTN post TIPS measured
      1.16 +/- 0.06 m/s, 2.48 +/- 0.39 m/s, and 2.37 +/- 0.28 m/s, respectively. The
      MSV of the spleen in healthy subjects, patients with PHTN pre TIPS and patients
      with PHTN post TIPS measured 2.22 +/- 0.22 m/s, 3.65 +/- 0.32 m/s, and 3.27 +/-
      0.30 m/s, respectively. There were significant differences in MSV of the liver
      and spleen between healthy subjects and patients with PHTN (all P<.001). There
      was no significant difference in MSV of the liver pre and post TIPS placement
      (P>.05). However, a statistically significant difference in MSV of the spleen pre
      and Post TIPS placement (P<.001) was demonstrated. In addition, we observed a
      significant difference in spleen index between healthy subjects and patients with
      PHTN (P<.001), as well as between pre and post TIPS placement (P<.01).
      CONCLUSION: The MSV of the spleen measured with ARFI correlates well with portal
      vein pressure. Hence, the spleen stiffness by means of MSV on ARFI imaging can be
      used as a quantitative marker in monitoring the portal vein pressure as the
      function of the TIPS.

PMID- 22370135
TI  - Orbital apex syndrome due to trigeminal perineural spread of sinonasal leprosy: a
      case report.
AB  - Leprosy is a granulomatous disease primarily affecting the skin and peripheral
      nerves caused by Mycobacterium leprae, but also significantly involving sinonasal
      cavities and cranial nerves. It continues to be a significant public health
      problem, and despite multidrug therapy, it can still cause significant morbidity.
      The awareness of cranial nerve, intracranial and orbital apex involvement as in
      our case is important for appropriate treatment measures.

PMID- 22370136
TI  - Giant ameloblastoma.
AB  - Ameloblastoma is the most frequent of the odontogenic tumors. We report a case of
      a giant ameloblastoma involving the maxillary region and describe its
      ultrasonography and computed tomography findings.

PMID- 22370137
TI  - Haddad syndrome presenting with abdominal distension associated with long-segment
      aganglionosis.
AB  - Haddad syndrome is a form of neurocristopathy characterized by a combination of
      congenital central hypoventilation syndrome and Hirschsprung disease (HD).
      Although Haddad syndrome is extremely rare, awareness of the combination of long
      segment HD in Haddad syndrome as well as radiographic manifestations may help to
      ensure a timely diagnosis as well as to facilitate optimal treatment of this
      unusual condition. We report a case of Haddad syndrome with long-segment,
      intestinal aganglionosis in a newborn infant. This report emphasizes the features
      of HD in children with Haddad syndrome and suggests that specific attention be
      given to its interpretation on plain radiographs.

PMID- 22370138
TI  - Debris-filled biliary system: a difficult diagnosis on MRI and MRCP.
AB  - We describe a debris-filled biliary system as a difficult diagnosis using
      magnetic resonance imaging and magnetic resonance cholangiopancreatography
      (MRCP). A male patient aged 60 years showed a nonvisualized biliary system due to
      complete filling with debris. The following imaging features were observed: mild
      heterogeneity of intermediate signal on T2-weighted, MRCP and T1-weighted images
      and mild heterogeneous enhancement of periportal tissue on early and late
      postcontrast images. The absence of simple-appearing bile on T2 or MRCP images
      made the diagnosis of dilated, debris-filled biliary system challenging.

PMID- 22370139
TI  - Radiology-pathology conference: primary adrenal lymphoma.
AB  - We present a case of a 62-year-old man with a history of type II diabetes
      mellitus who presented to our emergency department with back pain and right upper
      quadrant abdominal pain associated with vomiting and weight loss. A computed
      tomographic scan of the abdomen and pelvis demonstrated a large adrenal mass, and
      subsequent biopsy showed primary adrenal lymphoma.

PMID- 22370140
TI  - Iodinated contrast media and its influence in emphysema CT measurements.

PMID- 22370141
TI  - Signal quality measures for unsupervised blood pressure measurement.
AB  - Accurate systolic and diastolic pressure estimation, using automated blood
      pressure measurement, is difficult to achieve when the transduced signals are
      contaminated with noise or interference, such as movement artifact. This study
      presents an algorithm for automated signal quality assessment in blood pressure
      measurement by determining the feasibility of accurately detecting systolic and
      diastolic pressures when corrupted with various levels of movement artifact. The
      performance of the proposed algorithm is compared to a manually annotated
      reference scoring (RS). Based on visual representations and audible playback of
      Korotkoff sounds, the creation of the RS involved two experts identifying
      sections of the recorded sounds and annotating sections of noise contamination.
      The experts determined the systolic and diastolic pressure in 100 recorded
      Korotkoff sound recordings, using a simultaneous electrocardiograph as a
      reference signal. The recorded Korotkoff sounds were acquired from 25 healthy
      subjects (16 men and 9 women) with a total of four measurements per subject. Two
      of these measurements contained purposely induced noise artifact caused by
      subject movement. Morphological changes in the cuff pressure signal and the width
      of the Korotkoff pulse were extracted features which were believed to be
      correlated with the noise presence in the recorded Korotkoff sounds. Verification
      of reliable Korotkoff pulses was also performed using extracted features from the
      oscillometric waveform as recorded from the inflatable cuff. The time between an
      identified noise section and a verified Korotkoff pulse was the key feature used
      to determine the validity of possible systolic and diastolic pressures in noise
      contaminated Korotkoff sounds. The performance of the algorithm was assessed
      based on the ability to: verify if a signal was contaminated with any noise; the
      accuracy, sensitivity and specificity of this noise classification, and the
      systolic and diastolic pressure differences between the result obtained from the
      algorithm and the RS. 90% of the actual noise contaminated signals were correctly
      identified, and a sample-wise accuracy, sensitivity and specificity of 97.0%,
      80.61% and 98.16%, respectively, were obtained from 100 pooled signals. The mean
      systolic and diastolic differences were 0.37 +/- 3.31 and 3.10 +/- 5.46 mmHg,
      respectively, when the artifact detection algorithm was utilized, with the
      algorithm correctly determined if the signal was clean enough to attempt an
      estimation of systolic or diastolic pressures in 93% of blood pressure
      measurements.

PMID- 22370142
TI  - Electrical activity as a developmental regulator in the formation of spinal cord
      circuits.
AB  - Spinal cord development is a complex process involving generation of the
      appropriate number of cells, acquisition of distinctive phenotypes and
      establishment of functional connections that enable execution of critical
      functions such as sensation and locomotion. Here we review the basic cellular
      events occurring during spinal cord development, highlighting studies that
      demonstrate the roles of electrical activity in this process. We conclude that
      the participation of different forms of electrical activity is evident from the
      beginning of spinal cord development and intermingles with other developmental
      cues and programs to implement dynamic and integrated control of spinal cord
      function.

PMID- 22370143
TI  - Ameliorative effects of diammonium glycyrrhizinate on inflammation in focal
      cerebral ischemic-reperfusion injury.
AB  - The present study investigated the neuroprotective potential of Diammonium
      Glycyrrhizinate (DG) in focal cerebral ischemic-reperfusion (IR) injury in mice.
      The middle cerebral artery occlusion (MCAO) model of the mouse was used. Mice
      were treated with DG (20mg/kg per day, intraperitoneal injection) or saline as
      control, from the beginning of the reperfusion to 7 days. The focal cerebral IR
      injury resulted in significant neurological deficits, infarct size, and brain
      water content (BWC) at 1 day, 3 days and 7 days after MCAO. A significant
      increase in various inflammatory mediators like interleukin-1 (IL-1), tumor
      necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), inducible nitric
      oxide synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) and astrocytic glial
      fibrillary acidic protein (GFAP) was also observed in the IR challenged brains.
      The DG treatment significantly improved neurofunction, decreased infarct size,
      and suppressed edema in the focal cerebral IR injury. The neuroprotective effect
      of DG was found to be associated with significant reduction in the IL-1, TNF
      alpha, COX-2, iNOS, NF-kappaB and GFAP levels. In summary, this study suggested
      that DG has a neuroprotective effect on cerebral IR injury and this effect is
      likely related to DG's anti-inflammatory function.

PMID- 22370144
TI  - Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron
      loading.
AB  - Severe disruption of brain iron homeostasis can cause fatal neurodegenerative
      disease, however debate surrounds the neurologic effects of milder, more common
      iron loading disorders such as hereditary hemochromatosis, which is usually
      caused by loss-of-function polymorphisms in the HFE gene. There is evidence from
      both human and animal studies that HFE gene variants may affect brain function
      and modify risks of brain disease. To investigate how disruption of HFE
      influences brain transcript levels, we used microarray and real-time reverse
      transcription polymerase chain reaction to assess the brain transcriptome in Hfe(
      /-) mice relative to wildtype AKR controls (age 10 weeks, n>=4/group). The Hfe(-/
      ) mouse brain showed numerous significant changes in transcript levels (p<0.05)
      although few of these related to proteins directly involved in iron homeostasis.
      There were robust changes of at least 2-fold in levels of transcripts for
      prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene
      Fos, early growth response genes), neurotransmission (glutamate NMDA receptor
      Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory
      (calcium/calmodulin-dependent protein kinase IIalpha Camk2a). As previously
      reported for dietary iron-supplemented mice, there were altered levels of
      transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease
      characterized by excessive lipofuscin deposition. Labile iron is known to enhance
      lipofuscin generation which may accelerate brain aging. The findings provide
      evidence that iron loading disorders can considerably perturb levels of
      transcripts for genes essential for normal brain function and may help explain
      some of the neurologic signs and symptoms reported in hemochromatosis patients.

PMID- 22370145
TI  - A(2A)/D(2) receptor heteromerization in a model of Parkinson's disease. Focus on
      striatal aminoacidergic signaling.
AB  - The present manuscript mainly summarizes the basic concepts and the molecular
      mechanisms underlying adenosine A(2A)-dopamine D(2) receptor-receptor
      interactions in the basal ganglia. Special emphasis is placed on neurochemical,
      behavioral and electrophysiological findings supporting the functional role that
      A(2A)/D(2) heteromeric receptor complexes located on striato-pallidal GABA
      neurons and corticostriatal glutamate terminals play in the regulation of the so
      called "basal ganglia indirect pathway". Furthermore, the role of A(2A)/mGluR(5)
      synergistic interactions in striatal neuron function and dysfunction is
      discussed. The functional consequences of the interactions between striatal
      adenosine A(2A), mGluR(5) and dopamine D(2) receptors on striatopallidal GABA
      release and motor behavior dysfunctions suggest the possibility of simultaneously
      targeting these receptors in Parkinson's disease treatment. This article is part
      of a Special Issue entitled Brain Integration. This article is part of a Special
      Issue entitled: Brain Integration.

PMID- 22370146
TI  - Marked synergism between mutant SOD1 and glutamate transport inhibition in the
      induction of motor neuronal degeneration in spinal cord slice cultures.
AB  - Loss of astrocytic glutamate transport capacity in ALS spinal cord supports an
      excitotoxic contribution to motor neuron (MN) damage in the disease, and dominant
      gain of function mutations in Cu/Zn superoxide dismutase (SOD1) cause certain
      familial forms of ALS. We have used organotypic slice cultures from wild type and
      G93A SOD1 mutant rat spinal cords to examine interactions between excitotoxicity
      and the presence of mutant SOD1 in the induction of MN degeneration. Slice
      cultures were prepared from 1 week old pups, and after an additional week in
      vitro, some were exposed to either a low level (30 MUM) of the glutamate uptake
      inhibitor, trans-pyrrolidine-2,4-dicarboxylic acid (PDC) for 3 weeks, or a higher
      level (50 MUM) for 48 h, followed by histochemical labeling to assess MN injury.
      In wild type animals these exposures caused relatively little MN degeneration.
      Similarly, little MN degeneration was seen in slices from SOD1 mutant animals
      that were not exposed to PDC. However, addition of PDC to SOD1 mutant slices
      resulted in substantial MN injury, which was markedly attenuated by a Ca2+
      permeable AMPA-type (Ca-AMPA) glutamate channel blocker, or by a nitric oxide
      synthase antagonist. These observations illustrate the utility of the organotypic
      culture model for the investigation of intracellular interactions underlying MN
      degeneration in ALS, and support the hypothesis that activation of Ca-AMPA
      channels on MNs provides a metabolic burden that synergizes with deleterious
      effects of mutant SOD1 in the induction of MN injury.

PMID- 22370147
TI  - Safety evaluation of vitamin A in growing dogs.
AB  - The safe upper limit for inclusion of vitamin A in complete diets for growing
      dogs is uncertain, with the result that current recommendations range from 5.24
      to 104.80 MUmol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal)
      metabolisable energy (ME). The aim of the present study was to determine the
      effect of feeding four concentrations of vitamin A to puppies from weaning until
      1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever
      and Miniature Schnauzer, were randomly assigned to one of four treatment groups.
      Following weaning at 8 weeks of age, puppies were fed a complete food
      supplemented with retinyl acetate diluted in vegetable oil and fed at 1 ml
      oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 MUmol
      retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME.
      Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36
      and 52 weeks of age and analysed for markers of vitamin A metabolism and markers
      of safety including haematological and biochemical variables, bone-specific
      alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I
      collagen and dual-energy X-ray absorptiometry. Clinical examinations were
      conducted every 4 weeks. Data were analysed by means of a mixed model analysis
      with Bonferroni corrections for multiple endpoints. There was no effect of
      vitamin A concentration on any of the parameters, with the exception of total
      serum retinyl esters, and no effect of dose on the number, type and duration of
      adverse events. We therefore propose that 104.80 MUmol retinol (100 000 IU
      vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the
      formulation of diets designed for puppy growth.

PMID- 22370148
TI  - Predictors of quality of life in inpatients with schizophrenia.
AB  - Shortening hospital stays has become a key focus in psychiatric care in recent
      years. However, patients with schizophrenia account for about 60% of inpatients
      in psychiatry departments in Japan. This study was designed to investigate the
      relationship between quality of life (QOL) and key indicators for long-term
      hospital stays among schizophrenia inpatients. A further aim was to elucidate the
      clinical determinants of QOL among long-stay inpatients. The study sample
      consisted of 217 inpatients with schizophrenia. Age, duration of illness,
      duration of hospitalization, years of education, body mass index, neurocognitive
      function, drug-induced extrapyramidal symptoms, involuntary movements,
      psychiatric symptoms, and dose equivalents of antipsychotics and anticholinergic
      agents were used as index factors. Pearson linear correlation and regression
      analyses were performed to examine the associations between QOL and the above
      mentioned factors. Negative symptoms, psychological discomfort, and resistance as
      rated on the Brief Psychiatric Rating Scale (BPRS) were correlated with all
      subscale scores of the Japanese version of the Schizophrenia Quality of Life
      Scale (JSQLS). Stepwise regression showed that negative symptoms, psychological
      discomfort, and resistance predicted the dysfunction of psycho-social activity
      score and the dysfunction of motivation and energy score on the JSQLS. This study
      shows that active treatment for negative symptoms, psychological discomfort, and
      resistance should be recommended to improve QOL among inpatients with
      schizophrenia.

PMID- 22370149
TI  - Recovered memory experience in a nonclinical sample is associated with
      dissociation rather than with aversive experiences.
AB  - Different hypotheses exist for the relationship among trauma, dissociation, and
      recovered memory. According to one view, recovered memory results from
      dissociation that a survivor adopts as a defense mechanism during a traumatizing
      event to avoid emotional pain. From this perspective, trauma is a necessary
      antecedent to relate dissociative symptoms with recovered memory. Another view
      emphasizes the characteristics of the victim, such as fantasy proneness and
      atypical cognitive operations. This alternate view holds that trauma is not
      necessary in relating dissociation to recovered memory. We tested these two
      hypotheses, measuring recovered memory, dissociative symptoms, childhood
      interpersonal adversity, and fantasy proneness in a nonclinical sample of college
      students. Our results showed a significant correlation between recovered memory
      and dissociative symptoms; the correlation cannot be accounted for by childhood
      interpersonal adversity, fantasy proneness, or absorption. Recovered events can
      be negative, neutral, or even positive. Trauma is not necessary in relating
      recovered memory to dissociative symptoms.

PMID- 22370150
TI  - Stressful life events and obsessive-compulsive disorder: clinical features and
      symptom dimensions.
AB  - The potential role of stressful life events (SLEs) in the genesis of obsessive
      compulsive disorder (OCD) has been suggested by several authors, but whether the
      number or the severity or the type of SLEs preceding the onset of OCD has a
      triggering effect is unclear. Further, sociodemographic and clinical features of
      OCD preceded by SLEs, and the relationship between type of SLEs and type of
      obsessive-compulsive symptomatology remain mainly unexplored. The aims of this
      study were to compare the clinical features of OCD with and without SLEs
      preceding it and to examine the relationship between type of SLEs and OCD symptom
      dimensions. The number and type of SLEs which occurred before the onset of OCD
      were determined in 329 patients: the raters had to decide whether an occurrence
      12 months before the onset of OCD would fit any of the 61 items on Paykel's list,
      and each event reported was carefully investigated in order to determine the
      exact time of occurrence. At least one event preceded the onset of OCD in 200
      patients (60.8%), and this was significantly associated with female gender,
      abrupt onset of the disorder and somatic obsessions. Moreover, LogReg Analysis
      identified three specific traumatic events ("hospitalization of a family member",
      "major personal physical illness", "loss of personally valuable object")
      significantly associated with a symptom dimension (symmetry obsessions,
      repeating, ordering/arranging, counting, and checking compulsions). Additional
      evidence regarding the association among SLE-preceded OCD, female gender, somatic
      obsessions and symmetry/ordering symptoms should be obtained to advance the
      understanding of OCD.

PMID- 22370151
TI  - Depression in youth with obsessive-compulsive disorder: clinical phenomenology
      and correlates.
AB  - This study examined differences in clinical presentation and functional
      impairment in youth with obsessive-compulsive disorder (OCD) with or without
      comorbid depressive disorders and sought to determine the predictors of youth
      reported depressive symptoms. One-hundred and sixty youth were reliably diagnosed
      with OCD and comorbid disorders using the Anxiety Disorders Interview Schedule
      for DSM-IV: Parent version (Silverman and Albano, 1996) and confirmed by an
      experienced clinician. Sixteen percent (n = 25) had a comorbid diagnosis of a
      current depressive disorder (DD). Significantly more females than males had a DD.
      Those with a DD showed increased OCD symptom severity, OCD-related functional
      impairment, and family accommodation relative to those without a comorbid DD.
      Depressive symptoms were significantly positively correlated with years of age,
      degree of OCD symptom severity, measures of OCD-related functional impairment,
      and non-OCD anxiety symptoms. Hierarchical regression analyses showed that age,
      gender, functional impairment, and non-OCD anxiety were significant predictors of
      depressive symptoms, even when OCD symptom severity was controlled. Notably,
      functional impairment was a partial mediator of the relationship between OCD
      symptom severity and depression levels, suggesting depression levels are the
      product of both degree of symptoms and amount of day-to-day impairment. Results
      are discussed in terms of implications for assessment and treatment.

PMID- 22370152
TI  - The CNR1 gene in depression and schizophrenia - is there an association with
      early improvement and response?

PMID- 22370153
TI  - Sensitivity to posed and genuine facial expressions of emotion in severe
      depression.
AB  - The aim of the current study was to investigate whether the ability to
      distinguish genuine from non-genuine (neutral or posed) facial expressions of
      emotion (happiness, sadness, fear and disgust) is impaired in depression, and
      whether improvement in this ability occurs with treatment response. Sixty-eight
      depressed inpatients and 50 matched healthy controls performed the Emotion
      Categorisation Task three times over 6 weeks. All participants showed some
      sensitivity to the meaningful differences between genuine and non-genuine
      expressions of emotion, with an increasing percentage of faces labelled as
      genuinely feeling the emotion from neutral to posed to genuine presentations.
      Depressed patients showed significantly less sensitivity in differentiating non
      genuine from genuine expressions of sadness, compared with healthy controls.
      Performance on the Emotion Categorisation Task did not change over time in
      treatment responders compared with treatment non-responders. These findings have
      implications for understanding why depressed individuals may have difficulties in
      social interactions.

PMID- 22370154
TI  - Psychosocial and neurocognitive functioning in unipolar and bipolar depression: a
      12-month prospective study.
AB  - Previous studies have revealed psychosocial and cognitive impairments in patients
      during unipolar and bipolar depression, which persist even in subsyndromal and
      euthymic states. Currently, little is known about the nature and the extent of
      psychosocial and cognitive deficits during depression. The aim of the present
      study was to characterize psychosocial and cognitive profiles among unipolar
      (MDD) and bipolar (BD) patients during a major depressive episode and to compare
      the profiles of the patient groups. Depressed patients with MDD (n=13) and BD
      (n=11) were followed over a period of 12 months. Clinical, psychosocial and
      neuropsychological assessments were conducted at baseline and at 6-week, 4-month,
      8-month and 12-month follow-ups. In the case of severe mood disorders,
      psychosocial and neurocognitive functioning seem similar among MDD and BD
      patients during a depressive episode. All MDD and BD patients had global
      psychosocial dysfunction, characterized by occupational and relational
      impairments. Furthermore, the neurocognitive profile was heterogeneous with
      regard to the nature and extent of cognitive deficits but attentional processes
      were frequently compromised. After 1 year of treatment, occupational and
      relational impairments, as well as neurocognitive dysfunction, persisted
      sufficiently to alter daily functioning.

PMID- 22370155
TI  - Measurement of waist circumference at different sites affects the detection of
      abdominal obesity and metabolic syndrome among psychiatric patients.
AB  - There is a lack of understanding about the impact of different waist
      circumference (WC) measurements on the detection of abdominal obesity and
      metabolic syndrome in psychiatric patients. This cross-sectional study included a
      total of 382 inpatients with schizophrenia-related disorders to assess each
      component of metabolic syndrome. WC was measured at the lowest rib, midpoint
      between the iliac crest and lowest rib, iliac crest, minimal waist, and
      umbilicus. Logistic regression analysis was performed to examine the ability of
      WC at each site to predict the presence of metabolic risk clustering. The mean WC
      values for all sites were significantly different from each other. The
      measurement site had an influence on the prevalence of abdominal obesity (30
      38.2% in men and 53.9-86.3% in women). The influence on the prevalence of
      metabolic syndrome was greater with the International Diabetes Federation (IDF)
      criteria (19.3-23.9% in men and 29.4-43.1% in women) than with the Adult
      Treatment Panel III (ATP III) criteria (26.1-28.6% in men and 37.3-44.1% in
      women). The areas under the receiver operating characteristic curve for metabolic
      risk clustering were highest at the umbilicus and midpoint. Given that the WC
      measurement protocol has substantial influence on the prevalence of abdominal
      obesity and metabolic syndrome, a predefined measurement site is required for all
      psychiatric studies.

PMID- 22370156
TI  - Psychological characteristics of early remitters in patients with panic disorder.
AB  - We aimed to examine whether anxiety sensitivity and agoraphobic fear could affect
      the time taken to remission after 24 weeks of open-label escitalopram treatment
      of patients with panic disorder (PD). We recruited 158 patients, and 101 patients
      completed the study. Clinical severity and psychological characteristics were
      assessed at baseline and 4, 12, and 24 weeks after the treatment, using the
      Clinical Global Impression-Severity (CGI-S), the Hamilton Rating Scales for
      Anxiety and Depression, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany
      Panic and Phobia Questionnaire (APPQ), and the Panic Disorder Severity Scale
      (PDSS). Remission was defined as the absence of full panic attacks and PDSS
      scores of 7 or less. Completing patients were stratified according to the time
      taken to remit: early (n=20) and late (n=58) remission and non-remission groups
      (n=23). There were no significant differences among the three groups at baseline
      on the CGI-S and the PDSS mean scores. However, early remitters had significantly
      lower scores than late remitters and non-remitters on the ASI-R and APPQ. In
      conclusion, anxiety sensitivity and agoraphobic fear can affect the time to
      remission after pharmacotherapy, and clinicians should consider the psychological
      characteristics of PD patients in order to achieve an optimal response to
      pharmacotherapy.

PMID- 22370158
TI  - Functional inactivation of thyroid transcription factor-1 in PCCl3 thyroid cells.
AB  - Thyroid transcription factor-1 (TTF-1) is a key regulator of thyroid development
      and function. In order to identify the genes whose expression depends on TTF-1
      transcriptional activity within the thyrocyte we analyzed the consequence of the
      functional inactivation of this factor in PCCl3 cells. The expression of a fusion
      protein composed of the DNA binding domain of TTF-1 and of the strong repressive
      domain of the engrailed protein resulted in a dramatic loss of epithelial cell
      morphology and in proliferation arrest. These changes were reversed when the
      inhibition of endogenous TTF-1 was relieved. No change was observed when a
      similar fusion protein containing point mutations abolishing DNA binding activity
      was produced in the cells. Besides the expected down-regulation of expression of
      the main genes linked to the differentiated thyroid function, we observed a
      decreased expression of the transcription factors Hhex, Pax 8 and TTF-2 and of E
      cadherin. By contrast, both ThOX-1 and DUOXA-1 genes were up-regulated, as well
      as the ones encoding vimentin and several proteins involved in cell cycle arrest.
      Our data thus extend the known roles of TTF-1 in thyroid development and in the
      expression of differentiated function in the adult organ to the control of
      epithelial morphology and of cell division in mature thyrocytes.

PMID- 22370157
TI  - Phosphorylation of human estrogen receptor-beta at serine 105 inhibits breast
      cancer cell migration and invasion.
AB  - Multiple phosphorylation sites on the human estrogen receptor (hER)alpha were
      identified and shown to influence mammary carcinogenesis. In contrast, functional
      phosphorylation sites of hERbeta have yet to be experimentally identified and
      validated. Here, using mass spectrometry, we uncovered three serines (S75, S87,
      and S105) in the N-terminus of hERbeta as targets of ERK1/2 and p38 kinases. We
      raised a specific antibody against phosphorylated S105 (pS105) and demonstrated
      that this site was endogenously phosphorylated in MDA-MB-231 and BT-474 cells. A
      phospho-mimetic mutant generated from hERbeta1 was found to exhibit higher
      transactivation activity than hERbeta1. Ectopic expression of this mutant
      inhibited cell migration and invasion, but did not affect cell growth and cell
      cycle progression in these cell models. In breast cancer specimens, pS105-hERbeta
      immunoreactivity was detected with a higher prevalence and intensity than that of
      hERbeta1. These results underscore the functional importance of the first
      experimentally identified hERbeta-phosphorylation site in breast cancer.

PMID- 22370160
TI  - Pharmacokinetic-directed high-dose busulfan combined with cyclophosphamide and
      etoposide results in predictable drug levels and durable long-term survival in
      lymphoma patients undergoing autologous stem cell transplantation.
AB  - The clinical advantage of pharmacokinetic (PK)-directed-based dosing on
      intravenous (i.v.) versus oral busulfan-related toxicity and survival remains
      unclear. We performed a retrospective cohort study of sequential cohorts of
      patients comparing PK-directed oral and i.v. busulfan-based conditioning regimens
      in lymphoma patients undergoing autologous hematopoietic cell transplantation
      (ASCT). Patients received oral (n = 95), every 6 hours i.v. (IV16, n = 113), or
      once-daily i.v. (IV4, n = 86) busulfan, cyclophosphamide, and etoposide. PK
      directed dosing was performed to achieve a predefined target area under the curve
      (AUC) of 20,000 MUM-min (range: 18,400-21,600 MUM-min). PK-directed dose
      adjustments markedly reduced the number of patients in the oral group with total
      AUC higher than the targeted AUC range, and reduced the variations of total AUC
      values in all patient groups. One hundred-day mortality was 2.1%, 3.6%, and 3.5%
      for oral, IV16, and IV4 cohorts, respectively. Five-year overall survival (OS)
      was 57% (95% confidence interval [CI] 45%-66%) and 64% (95% CI 53%-73%) for
      patients who received oral and i.v. busulfan, respectively. Both multivariable
      and instrumental variable analyses indicated the route of delivery had no
      significant impact on OS, whereas refractory disease and age >=55 were
      significantly associated with poorer OS. In lymphoma patients undergoing ASCT, PK
      directed i.v. or oral busulfan-based conditioning regimens have comparable
      toxicity and OS.

PMID- 22370159
TI  - The inositol 5-phosphatase SHIP-1 and adaptors Dok-1 and 2 play central roles in
      CD4-mediated inhibitory signaling.
AB  - CD4 functions to enhance the sensitivity of T cells to antigenic peptide/MHC
      class II. However, if aggregated in isolation, e.g. in the absence of T cell
      receptor (TCR), CD4 can transduce yet undefined signals that lead to T cell
      unresponsiveness to antigen and apoptosis. In Human Immunodeficiency Virus-1 (HIV
      1) disease, CD4(+) T cell loss can result from gp120-induced CD4 signaling in
      uninfected cells. We show here that CD4 aggregation leads to Lck-dependent
      phosphorylation of the RasGAP adaptors Downstream of kinase-1/2 (Dok-1/2) and the
      inositol 5-phosphatase-1 (SHIP-1) and association of the two molecules. Studies
      using SHIP-1 shRNA, knockout mice and decoy inhibitors further indicate that CD4
      mediated inhibition of TCR-mediated T cell activation is SHIP-1 and Dok-1/2
      dependent, and involves SHIP-1 hydrolysis of Phosphatidylinositol 3,4,5
      trisphosophate (PI(3,4,5)P3) needed for TCR signaling. Our studies provide
      evidence for a novel mechanism by which ill-timed CD4-mediated signals activated
      by ligands such as HIV-1 gp120 lead to disarmament of the immune system.

PMID- 22370161
TI  - The superconducting transition temperatures of Fe(1+x)Se(1-y), Fe(1+x)Se(1
      y)Te(y) and (K/Rb/Cs)(z)Fe(2-x)Se2.
AB  - In a recent contribution to this journal, it was shown that the transition
      temperatures of optimal high-T(C) compounds obey the algebraic relation T(C0) =
      k(-1)(B)/lzeta, where l is related to the mean spacing between interacting
      charges in the layers, zeta is the distance between interacting electronic
      layers, beta is a universal constant and k(B) is Boltzmann's constant. The
      equation was derived assuming pairing based on interlayer Coulomb interactions
      between physically separated charges. This theory was initially validated for 31
      compounds from five different high-T(C) families (within an accuracy of +/-1.37
      K). Herein we report the addition of Fe(1+x)Se(1-y) and Fe(1+x)Se(1-y)Te(y) (both
      optimized under pressure) and A(z)Fe(2-x)Se(2) (for A = K, Rb or Cs) to the
      growing list of Coulomb-mediated superconducting compounds in which T(C0) is
      determined by the above equation. Doping in these materials is accomplished
      through the introduction of excess Fe and/or Se deficiency, or a combination of
      alkali metal and Fe vacancies. Consequently, a very small number of vacancies or
      interstitials can induce a superconducting state with a substantial transition
      temperature. The confirmation of the above equation for these Se-based Fe
      chalcogenides increases to six the number of superconducting families for which
      the transition temperature can be accurately predicted.

PMID- 22370162
TI  - Proteomic analysis by SILAC and 2D-DIGE reveals radiation-induced endothelial
      response: four key pathways.
AB  - Epidemiological data show that ionising radiation increases the risk of
      cardiovascular disease. The endothelium is one of the main targets of radiation
      induced damage. Rapid radiation-induced alterations in the biological processes
      were investigated after exposure to a clinically relevant radiation dose (2.5 Gy
      gamma radiation). The changes in protein expression were determined using the
      human endothelial cell line EA.hy926 as a model. Two complementary proteomic
      approaches, SILAC (Stable Isotope Labelling with Amino acids in Cell culture) and
      2D-DIGE (Two Dimensional Difference-in-Gel-Electrophoresis) were used. The
      proteomes of the endothelial cells were analysed 4h and 24h after irradiation.
      Differentially expressed proteins were identified and quantified by MALDI-TOF/TOF
      and LTQ Orbitrap tandem mass spectrometry. The deregulated proteins were mainly
      categorised in four key pathways: (i) glycolysis/gluconeogenesis and
      synthesis/degradation of ketone bodies, (ii) oxidative phosphorylation, (iii) Rho
      mediated cell motility and (iv) non-homologous end joining. We suggest that these
      alterations facilitate the repair processes needed to overcome the stress caused
      by irradiation and are indicative of the vascular damage leading to radiation
      induced cardio- and cerebrovascular impairment.

PMID- 22370163
TI  - DIGE enables the detection of a putative serum biomarker of fungal origin in a
      mouse model of invasive aspergillosis.
AB  - Invasive aspergillosis (IA) is a major threat for immunocompromised patients.
      Diagnostic difficulties often delay specific treatment initiation, which
      increases mortality. Finding new biomarkers to improve and speed accurate
      diagnosis is thus vital. To investigate the ability of proteomic methods for
      discovering new biomarkers of IA, we used a DIGE approach to perform a proteomic
      analysis on both bronchoalveolar lavages (BAL) and sera at different time-points
      of infection in a mouse model of invasive pulmonary aspergillosis. Progression of
      the infection was monitored using a bioluminescent strain of Aspergillus
      fumigatus. Sera proteins were enriched using the ProteoMiner kit (Biorad). This
      method allowed us to identify a fungal protein, the A. fumigatus major allergen
      Asp f 2, in sera of mice one day after the infection. However, this fungal
      protein was not detected three days after the infection. Importantly, in BAL,
      this work provides evidence of an in vivo complement evasion mechanism through
      the cleavage of C3b into three fragments during aspergillosis. Finally, our
      results underlining the inflammatory host response to IA in both lung and blood
      compartments at different times of infection may provide new insights into the
      pathophysiology of this disease.

PMID- 22370164
TI  - Time-dependent changes in protein expression in rainbow trout muscle following
      hypoxia.
AB  - Adaptation to hypoxia is a complex process, and individual proteins will be up-
      or down-regulated in order to address the main challenges at any given time. To
      investigate the dynamics of the adaptation, rainbow trout (Oncorhynchus mykiss)
      was exposed to 30% of normal oxygen tension for 1, 2, 5 and 24 h respectively,
      after which muscle samples were taken. The successful investigation of numerous
      proteins in a single study was achieved by selectively separating the
      sarcoplasmic proteins using 2-DE. In total 46 protein spots were identified as
      changing in abundance in response to hypoxia using one-way ANOVA and multivariate
      data analysis. Proteins of interest were subsequently identified by MS/MS
      following tryptic digestion. The observed regulation following hypoxia in
      skeletal muscle was determined to be time specific, as only a limited number of
      proteins were regulated in response to more than one time point. The cellular
      response to hypoxia included regulation of proteins involved in maintaining iron
      homeostasis, energy levels and muscle structure. In conclusion, this proteome
      based study presents a comprehensive investigation of the expression profiles of
      numerous proteins at four different time points. This increases our understanding
      of timed changes in protein expression in rainbow trout muscle following hypoxia.

PMID- 22370165
TI  - Molecular epidemiology of human Campylobacter jejuni shows association between
      seasonal and international patterns of disease.
AB  - We sought to explain seasonality and other aspects of Campylobacter jejuni
      epidemiology by integrating population genetic and epidemiological analysis in a
      large 3-year longitudinal, two-centre, population-based study. Epidemiological
      information was collected for 1505 isolates, which were multilocus sequence
      typed. Analyses compared pathogen population structure between areas, over time,
      and between clinical presentations. Pooled analysis was performed with published
      international datasets. Subtype association with virulence was not observed. UK
      sites had nearly identical C. jejuni populations. A clade formed by ST45 and
      ST283 clonal complexes showed a summer peak. This clade was common in a Finnish
      dataset but not in New Zealand and Australian collections, countries with less
      marked seasonality. The UK, New Zealand and Australian collections were otherwise
      similar. These findings map to known in-vitro differences of this clade. This
      identifies a target for studies to elucidate the drivers of the summer peak in
      human C. jejuni infection.

PMID- 22370166
TI  - Treatment of Cheyne-Stokes respiration-central sleep apnea in patients with heart
      failure.
AB  - Sleep disordered breathing including obstructive sleep apnea (OSA) and central
      sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) is often accompanied by
      heart failure. Treatment of OSA centered on continuous positive airway pressure
      (CPAP) is established. However, treatment of CSR-CSA is still controversial.
      Since CSR-CSA occurs as a consequence of heart failure, optimization of heart
      failure is essential to treat CSR-CSA. For treatment directed at CSR-CSA itself,
      a variety of treatment approaches including night oxygen therapy and noninvasive
      positive pressure ventilation have been applied. Among them, night oxygen therapy
      improves patients' symptoms, quality of life (QOL), and left ventricular
      function, but had yet been shown to improve clinical outcome. For CPAP, there are
      responders and non-responders and for responders CPAP can also improve survival.
      Adaptive servo-ventilation (ASV), which most effectively treats CSR-CSA, improves
      exercise capacity, QOL, and cardiac function. Recent reports suggested ASV may
      also prevent cardiac events in patients with heart failure. However, further
      studies are needed to conclude that this treatment improves patient survival.

PMID- 22370167
TI  - A possible mechanism of basic fibroblast growth factor-promoted scarless wound
      healing: the induction of myofibroblast apoptosis.
AB  - Although recent clinical reports have indicated that recombinant basic fibroblast
      growth factor (bFGF) promotes scarless wound healing, the mechanism remains
      unclear. The present study was carried out to elucidate the mechanisms. The
      protein levels of cellular alpha-smooth muscle actin increased at 2-4 days after
      TGFbeta treatment alone and at 4 to 6 days after a costimulation of bFGF and
      TGFbeta. A spontaneous contraction of stressed myofibroblast-collagen matrix was
      cancelled by bFGF, which was restored under the presence of C3 exotransferase or
      Y27632. bFGF stimulation of myofibroblasts as well as fibroblasts elicited a
      transient Rac and Rho activation. bFGF promoted apoptosis of the myofibroblasts
      but not of the fibroblasts, even in the presence of two different inhibitors,
      either LY294002 or an Akt inhibitor. The present study suggests that the
      phosphatidylinositol-3-kinase to Akt as well as the Rho to Rho kinase signaling
      pathway is involved in bFGF-promoted myofibroblast apoptosis, and bFGF can
      promote the scarless wound healing upon the induction of apoptosis of
      myofibroblasts, but not fibroblasts.

PMID- 22370169
TI  - Rotation abroad: why do it?

PMID- 22370168
TI  - Characterisation of inflammatory infiltrates in lesions of the oral mucosa, skin,
      and bronchioles in a case of paraneoplastic pemphigus.

PMID- 22370171
TI  - sQUIZ your knowledge! "Water-drop" lesions in a febrile patient. Miliaria
      crystalline (MC).

PMID- 22370172
TI  - (Carpe)DIEM - dermatological indications for electron microscopy: Amyloid
      deposition. [corrected].

PMID- 22370174
TI  - Supersonic shear imaging provides a reliable measurement of resting muscle shear
      elastic modulus.
AB  - The aim of the present study was to assess the reliability of shear elastic
      modulus measurements performed using supersonic shear imaging (SSI) in nine
      resting muscles (i.e. gastrocnemius medialis, tibialis anterior, vastus
      lateralis, rectus femoris, triceps brachii, biceps brachii, brachioradialis,
      adductor pollicis obliquus and abductor digiti minimi) of different architectures
      and typologies. Thirty healthy subjects were randomly assigned to the intra
      session reliability (n = 20), inter-day reliability (n = 21) and the inter
      observer reliability (n = 16) experiments. Muscle shear elastic modulus ranged
      from 2.99 (gastrocnemius medialis) to 4.50 kPa (adductor digiti minimi and
      tibialis anterior). On the whole, very good reliability was observed, with a
      coefficient of variation (CV) ranging from 4.6% to 8%, except for the inter
      operator reliability of adductor pollicis obliquus (CV = 11.5%). The intraclass
      correlation coefficients were good (0.871 +/- 0.045 for the intra-session
      reliability, 0.815 +/- 0.065 for the inter-day reliability and 0.709 +/- 0.141
      for the inter-observer reliability). Both the reliability and the ease of use of
      SSI make it a potentially interesting technique that would be of benefit to
      fundamental, applied and clinical research projects that need an accurate
      assessment of muscle mechanical properties.

PMID- 22370175
TI  - Electrosprayed hydroxyapatite on polymer nanofibers to differentiate mesenchymal
      stem cells to osteogenesis.
AB  - Electrospraying of hydroxyapatite (HA) nanoparticles onto the surface of polymer
      nanofibers provides a potentially novel substrate for the adhesion, proliferation
      and differentiation of mesenchymal stem cells (MSCs) into bone tissue
      regeneration. HA nanoparticles (4%) were electrosprayed on the surface of
      electrospun polycaprolactone (PCL) nanofibers (420 +/- 15 nm) for bone tissue
      engineering. PCL/HA nanofibers were comparatively characterized with PCL/Collagen
      (275 +/- 56 nm) nanofibers by FT-IR analysis to confirm the presence of HA.
      Fabricated PCL/HA and PCL/Collagen nanofibers and TCP (control) were used for the
      differentiation of equine MSC into osteogenic lineages in the presence of
      DMEM/F12 medium supplemented with beta-glycerophosphate, ascorbic acid and
      dexamethasone. Cell proliferation and differentiation into an osteogenic lineage
      was evaluated by MTS assay, SEM observation, ALP activity, ARS staining,
      quantification of mineral deposition and expression of osteocalcin. Proliferation
      of MSCs increased significantly (P ? 0.05) up to 12% in PCL/Collagen (day 15)
      compared to PCL/HA nanofibrous substrate. ALP activity was increased 20% in
      PCL/HA by day 10 confirming the direction of osteogenic lineage from MSCs
      differentiation. PCL/HA stimulated an increased mineral secretion up to 26% by
      day 15 on ARS staining compared to PCL/Collagen nanofibers and showing cuboidal
      morphology by expressing osteocalcin. These results confirmed that the
      specifically fabricated PCL/HA composite nanofibrous substrate enhanced the
      differentiation of MSCs into osteogenesis.

PMID- 22370176
TI  - Hydrophobication and characterisation of O-acetyl-galactoglucomannan for
      papermaking and barrier applications.
AB  - Norway spruce O-acetyl-galactoglucomannans (GGM) are water-soluble hemicelluloses
      that have potential to be produced in large scale as a side product of the
      mechanical pulping industry or by hot-water extraction of wood. Chemical
      modification is often needed to tailor such water-soluble polysaccharides into
      industrially valuable compounds. In this work, treatment of GGM with butyric and
      benzoic anhydride in pyridine/dimethylformamide rendered GGM derivatives, which
      were hydrophobic and partially soluble in organic solvents. The degree of
      substitution can be adjusted by varying the quantity of the reagent and reaction
      temperature. The dn/dc value for the benzoyl ester of GGM was determined in 0.05
      M LiBr DMSO in order to obtain accurate molar mass analysis with SEC-MALLS-RI.
      Novel substances with adjusted hydrophobicity can thus be prepared on one step
      synthesis from natural hemicelluloses, which then showed a slight increase in the
      molar mass upon esterification.

PMID- 22370177
TI  - 2-Allylphenyl glycosides as glycosyl donors for sugar coupling.
AB  - Glycosylations employing 2-allylphenyl glycoside, a new type of stable glycosyl
      donor, were optimized and explored with a variety of acceptors promoted by
      ICl/AgOTf. The utility of the protocol was further demonstrated with an efficient
      synthesis of the disaccharide fragment of bleomycins.

PMID- 22370178
TI  - Recombinant expression of chitosanase from Bacillus subtilis HD145 in Pichia
      pastoris.
AB  - A chitosanase-producing bacterium, Bacillus subtilis HD145 CCTCC AB 2010353, was
      isolated from a soil sample. The gene (csn) encoding chitosanase was cloned,
      sequenced, and expressed in the Pichia pastoris strain as a soluble and active
      form. Its expression level could be as high as 800 mg/L, and enzymatic activity
      reached approximately 9000 U/mg. The optimum pH and temperature were 5.5 and 50 
      degrees C, respectively. The recombinant protein was partially glycosylated. Its
      half lives at temperatures of 50 and 60  degrees C were 26 h and 23 min,
      respectively. Enzymatic activity was increased with an increasing degree of
      deacetylation of chitosan. The enzymatic productions of chitooligosaccharides
      from chitosans of various deacetylation degrees mainly ranged from chitobiose to
      chitopentamer.

PMID- 22370179
TI  - A novel class of sugar-based ether-linked-dispirooxindolo
      pyrrolidines/pyrrolizidines through [3+2]-cycloaddition of azomethine ylides.
AB  - An efficient one-pot synthesis of novel sugar based dispirooxindolo
      pyrrolidines/pyrrolizidines has been accomplished by a [3+2]-cycloaddition. This
      method utilizes an azomethine ylide derived from isatin and sarcosine/l-proline,
      with an ether linked alpha-,beta-unsaturated-beta-C-glycosidic ketones as the
      dipolarophile. All these sugar-based heterocyclics were characterized by NMR
      ((1)H and (13)C) and elemental analysis. Antimicrobial studies of sugar based
      dispiroheterocyclic compound 10 shows excellent activity against different
      microbes.

PMID- 22370180
TI  - The "RAPID" cognitive-behavioral therapy program for inattentive children:
      preliminary findings.
AB  - OBJECTIVE: The objectives of the current study were to ascertain feasibility and
      acceptability of directly delivering a cognitive-behavioral therapy (CBT) group
      intervention for inattentive children in a school setting, to examine the
      reliability of the RATE-CQuestionnaires that accompany the program, and to
      determine whether they can be used to measure outcome. METHOD: Eighty-eight
      parents/carers, their children (age 8-11), and teachers at mainstream primary
      schools in London participated by completing the RATE-C Questionnaires; 48
      participated in the group treatment following which the Questionnaires were
      readministered together with a semistructured interview. RESULTS: The
      intervention had a completion rate of 92%. Postgroup interviews supported the
      acceptability of a direct intervention with young children. Reliability of the
      RATE-C Total scores was excellent for parent/carer, child, and teacher ratings;
      postintervention parent/carer ratings indicated significant improvement on scales
      of attention, emotion, and conduct with medium to large effect. CONCLUSION: The
      results support the reliability of the RATE-C Scales, and feasibility and
      acceptability of the RAPID intervention.

PMID- 22370181
TI  - Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in
      patients with advanced cancer.
AB  - We hypothesised that host-related markers, possibly reflecting tumour
      aggressiveness, such as circulating endothelial cells (CEC) and circulating
      VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value
      in patients with advanced cancer enrolled in early anticancer drug development
      trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating
      VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-)
      cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1
      trials testing novel anti-vascular or anti-angiogenic agents. Correlations
      between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and
      biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and
      overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range
      0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0
      32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with
      CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD
      progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH
      prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of
      VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3,
      95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A
      composite VEGFR2(+)-BMD progenitor level/RHM score >= 2 was significantly
      associated with an increased risk of death compared to scores of 0 or 1 (median
      OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating
      VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when
      combined to classical clinical and biological parameters could provide a new tool
      for patient selection in early anticancer drug trials.

PMID- 22370182
TI  - Interrelated effects of dihomo-gamma-linolenic and arachidonic acids, and sesamin
      on hepatic fatty acid synthesis and oxidation in rats.
AB  - Interrelated effects of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid
      (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and
      oxidation were examined in rats. Rats were fed experimental diets supplemented
      with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100
      g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups
      fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared
      with maize oil strongly reduced the activity and mRNA levels of various lipogenic
      enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of
      lipogenic enzymes except for malic enzyme. The type of dietary fat was rather
      irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin
      free diets. Sesamin increased the activities of enzymes involved in fatty acid
      oxidation in all groups of rats given different fats. The extent of the increase
      depended on the dietary fat type, and the values became much higher with a diet
      containing sesamin and oil rich in ARA in combination than with a diet containing
      lignan and maize oil. Analyses of mRNA levels revealed that the combination of
      sesamin and oil rich in ARA compared with the combination of lignan and maize oil
      markedly increased the gene expression of various peroxisomal fatty acid
      oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin
      action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA
      but to a lesser extent.

PMID- 22370184
TI  - On display with transparent conducting films.

PMID- 22370183
TI  - Monocytes P2X7 purinergic receptor is modulated by glatiramer acetate in multiple
      sclerosis.
AB  - The aim of this study is to investigate the expression of P2X7R, IL-1beta and the
      ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS
      patients and to observe the possible effects of Glatiramer Acetate (GA) on such
      expression. Twelve RR treatment-free MS patients were selected and peripheral
      blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on
      monocytes was investigated by qrt-PCR. The in vitro effects of GA on the
      expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were
      evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS
      patients were given GA therapy and the monocytes obtained before treatment, after
      3 and 12 months of GA treatment were similarly investigated. No differences were
      found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS
      Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R
      (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07).
      Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found
      in HDs. GA in vivo treatment induced a reduction in the expression that was clear
      for P2X7R and CD39 (p<0.05) but only not significant for IL-1beta after 12 months
      of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta
      and CD39, and GA seems to interfere with such expression.

PMID- 22370185
TI  - Detection and characterization of Shiga toxin-producing Escherichia coli in
      faeces and lymphatic tissue of free-ranging deer.
AB  - Shiga toxin-producing Escherichia coli (STEC) have led to outbreaks worldwide and
      are considered emerging pathogens. Infections by STEC in humans have been
      reported after consumption of mainly beef, but also deer. This study investigated
      the occurrence of STEC in deer in Germany. The virulence genes eae, e-hlyA and
      saa, the stx subtypes, pulsed-field gel electrophoresis (PFGE) patterns and
      serovars were studied. In total, 120 samples of 60 animals were screened by real
      time polymerase chain reaction (PCR). The PCR results showed a high detection
      rate of stx genes (83%). Mainly faecal samples, but also some lymphatic tissue
      samples, tested stx-positive. All isolates carried stx2, were eae-negative and
      carried e-hlyA in 38% and saa in 9% of samples. Serovars (O88:[H8], O174:[H8],
      O146:H28) associated with human diseases were also identified. In some animals,
      isolates from lymphatic tissue and faecal samples showed undistinguishable PFGE
      patterns. The examined deer were shown to be relevant reservoirs of STEC with
      subtype stx2b predominating.

PMID- 22370186
TI  - Cell biology of molybdenum in plants and humans.
AB  - The transition element molybdenum (Mo) needs to be complexed by a special
      cofactor in order to gain catalytic activity. With the exception of bacterial Mo
      nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is bound to a
      pterin, thus forming the molybdenum cofactor Moco, which in different variants is
      the active compound at the catalytic site of all other Mo-containing enzymes. In
      eukaryotes, the most prominent Mo-enzymes are nitrate reductase, sulfite oxidase,
      xanthine dehydrogenase, aldehyde oxidase, and the mitochondrial amidoxime
      reductase. The biosynthesis of Moco involves the complex interaction of six
      proteins and is a process of four steps, which also requires iron, ATP and
      copper. After its synthesis, Moco is distributed to the apoproteins of Mo-enzymes
      by Moco-carrier/binding proteins. A deficiency in the biosynthesis of Moco has
      lethal consequences for the respective organisms. In humans, Moco deficiency is a
      severe inherited inborn error in metabolism resulting in severe neurodegeneration
      in newborns and causing early childhood death. This article is part of a Special
      Issue entitled: Cell Biology of Metals.

PMID- 22370187
TI  - Letter from the guest editor: pediatric body imaging, part II.

PMID- 22370188
TI  - Case of the season: Lemierre syndrome.

PMID- 22370189
TI  - Vascular malformations: classification and terminology the radiologist needs to
      know.

PMID- 22370190
TI  - Bowel imaging in children: a comprehensive look using US and MRI.

PMID- 22370191
TI  - Multidetector computed tomography evaluation of congenital mediastinal vascular
      anomalies in children.

PMID- 22370192
TI  - Imaging of pediatric thoracic trauma.

PMID- 22370193
TI  - Congenital causes of upper airway obstruction in pediatric patients: updated
      imaging techniques and review of imaging findings.

PMID- 22370194
TI  - Imaging evaluation of bowel obstruction in children: updates in imaging
      techniques and review of imaging findings.

PMID- 22370195
TI  - Magnetic resonance imaging assessment of sports-related musculoskeletal injury in
      children: current techniques and clinical applications.

PMID- 22370196
TI  - Imaging evaluation of pediatric trachea and bronchi: systematic review and
      updates.

PMID- 22370197
TI  - Forming connections in the homeopathic consultation.
AB  - OBJECTIVE: A previous study which explored homeopathic practitioners' in depth
      understanding and experiences of homeopathic consultations identified
      "connecting" as a key component of the consultation. This paper reports on
      "connecting" and its role in the consultation. METHOD: Using a qualitative
      grounded theory approach data was collected from homeopaths using in-depth
      interviews, observations of homeopathic consultations and solicited practitioner
      reflective diaries. Constant comparison assisted code, concept and category
      formation to form a model of the UK classical homeopathic consultation. RESULTS:
      "Connecting", describes a complex notion of relationship in the homeopathic
      consultation consisting of four dimensions, and performs several roles within the
      consultation that enable practitioners to elicit symptoms, identify expectations,
      assist with prescribing, help patients engage with homeopathic principles and
      stimulate healing. CONCLUSION: This study shows the homeopath as an important
      component of the therapeutic context forming complex relationships and using
      communication that is skills based and inductively shaped to interpret and
      respond to each individual patient and their narrative in the consultation.
      PRACTICE IMPLICATIONS: This study could have implications for teachers, students
      and practitioners of homeopathy by influencing training needs, and could prove
      instructive for other clinicians as homeopaths' communication style could be used
      to augment other consultations.

PMID- 22370198
TI  - Diagnosing women with HPV: the impact of diagnosis disclosure methods.
AB  - OBJECTIVE: Little data exists on women's HPV diagnosis encounters. This research
      focuses on impacts of the communicative medium used to inform women of their HPV
      status. We conducted a qualitative study to identify the mediums used to
      communicate HPV diagnoses and the impact of each medium on the diagnosis
      experience. METHOD: Twenty-five women with HPV completed semi-structured
      interviews, which we recorded and transcribed. We relied on grounded theory
      techniques in both data collection and analysis. RESULTS: There are three primary
      mediums health care providers use to inform women of their HPV diagnosis: phone
      calls, mailed letters/email, and face-to-face interactions. Implications
      regarding each medium are identified and discussed. CONCLUSION: There are
      drawbacks associated with the use of each medium that healthcare practitioners
      should be aware of and seek to avoid. PRACTICE IMPLICATIONS: Healthcare providers
      can utilize descriptions of diagnosis encounters and the recommendations
      accompanying them to understand and modify ways they choose to inform individuals
      of an HPV diagnosis.

PMID- 22370199
TI  - Variation and specialisation of the forcipular apparatus of centipedes
      (Arthropoda: Chilopoda): a comparative morphometric and microscopic investigation
      of an evolutionary novelty.
AB  - The forcipules of centipedes are the only known example in the animal kingdom of
      an evolutionary transition from walking legs to venom-injecting appendages. They
      provide a classic case of an evolutionary novelty under most (but not all)
      definitions of that concept. Although there is a reasonable literature on
      forcipules, and on the forcipular segment more generally, it is fragmentary and
      scattered. Also, many previous studies have been based on a single species and
      hence have no comparative component. Here, we build on this earlier literature by
      providing detailed qualitative and quantitative information on the forcipular
      segments of representatives of the five extant orders of centipedes. Our results
      reveal notable differences between the orders - as well as considerable variation
      within some of them. The pattern of inter-group differences can be used to infer,
      albeit cautiously, a major evolutionary trend from a presumed scutigeromorph-like
      last common ancestor (LCA), in which the forcipules were probably leg-like (as in
      present-day scutigeromorphs) to a more specialized claw-like structure with
      movement restricted to the horizontal plane. This morphological trend may reflect
      an ecological trend from open-habitat ambush predation to leaf-litter and
      subterranean predatory opportunism.

PMID- 22370200
TI  - Decolorization and degradation of azo dye--Reactive Violet 5R by an acclimatized
      indigenous bacterial mixed cultures-SB4 isolated from anthropogenic dye
      contaminated soil.
AB  - Azo dyes an important group of synthetic compounds are recalcitrant xenobiotics.
      Conventional technologies are unsuccessful to efficiently remove these compounds
      from contaminated environment. However, consorted metabolic functioning of innate
      microbial communities is a promising approach for bioremediation of polluted
      environment. Bacterial mixed cultures SB4 proficient in complete decolorization
      of azo dye - Reactive Violet 5R was developed through culture enrichment
      technique. Bacterial community composition based on 16S rRNA gene analysis
      revealed that mixed cultures SB4 composed of six bacterial strains namely
      Bacillus sp. V1DMK, Lysinibacillus sp. V3DMK, Bacillus sp. V5DMK, Bacillus sp.
      V7DMK, Ochrobacterium sp. V10DMK, Bacillus sp. V12DMK. SB4 grew well in minimal
      medium containing low amount of glucose and yeast extract (YE) (1 g/L) and
      decolorized 200mg/L of RV5 within 18 h under static condition. Mixed cultures SB4
      decolorized wide range of azo dyes and maximum rate of decolorization was
      observed at 37  degrees C and pH 7.0. Decolorization efficiency was found to be
      unaltered under high RV5 and salt concentration where 1500 mg/L of RV5 was
      decolorized in presence of 20 g/L NaCl. We propose the asymmetric cleavage of RV5
      and Fourier transformed infrared (FTIR), NMR and gas chromatography-mass
      spectrometry (GC-MS) confirmed the formation of four intermediatory compounds 1
      diazo-2-naphthol, 4-hydroxybenzenesulphonic acid, 2-naphthol and benzenesulphonic
      acid.

PMID- 22370201
TI  - Evaluation of copper slag to catalyze advanced oxidation processes for the
      removal of phenol in water.
AB  - The aim of this work was to evaluate the use of copper slag to catalyze phenol
      degradation in water by advanced oxidation processes (AOPs). Copper slag was
      tested in combination with H(2)O(2) (slag/H(2)O(2)) and H(2)O(2)/UV
      (slag/H(2)O(2)/UV). The studied methods promoted the complete photocatalytic
      degradation of phenol. Besides, they were able to reduce about 50% the TOC
      content in the samples. Slag/H(2)O(2)/UV and slag/H(2)O(2) treatments have
      favored biodegradability increment along the reaction time. Nevertheless, the
      irradiated method achieved higher values of the biodegradability indicator
      (BOD(5)/TOC). The toxicity assessment indicated the formation of more toxic
      compounds in both treatments. However, the control of the reaction time would
      minimize the environmental impact of the effluents.

PMID- 22370202
TI  - Determination of the risk of self-ignition of coals and biomass materials.
AB  - The safe storage, processing and handling of coals and biomass resources requires
      their tendency to self-ignite be understood; fires caused by self-ignition have
      occurred on many occasions in ports and at industrial plants. This work provides
      information on the tendency of several types of coal and four types of biomass to
      self-ignite. Data were obtained using the isothermal oven procedure and analyzed
      using the Frank-Kamenetskii method and a scaling procedure, both contemplated in
      standard EN15188. The results obtained throw light on the optimum volumes and
      storage times of the studied materials. The results also validate the methodology
      followed for determining the risk of self-ignition.

PMID- 22370203
TI  - Evolution of natural organic matter by size exclusion chromatography during
      photocatalytic degradation by solvothermal-synthesized titanium dioxide.
AB  - This study shows the effect of different titanium dioxides in transforming the
      structural properties of natural organic matter (NOM) during photocatalytic
      degradation with a solar UV light simulator. Titanium dioxide (TiO(2))
      synthesized by the sol-gel method coupled with the solvothermal technique and
      Degussa P-25 TiO(2) were used. The evolution of NOM degradation was followed by
      size exclusion chromatography with dissolved organic carbon, ultraviolet and
      fluorescence detection (SEC-DOC, SEC-UV(254) and SEC-Fl(254/450)). For both
      catalysts, there was a preferential degradation of the larger molecules of NOM
      into medium and smaller molecular size fractions. However, the synthesized TiO(2)
      was found to be more efficient than Degussa P-25 TiO(2) for DOC removal,
      especially UV(254) absorption and Fl(254/450) removal.

PMID- 22370204
TI  - Occurrence of different classes of perfluorinated compounds in Greek wastewater
      treatment plants and determination of their solid-water distribution
      coefficients.
AB  - The concentrations of eighteen perfluorinated compounds (PFCs: C5-C14
      carboxylates, C4, C6-C8 and C10 sulfonates and 3 sulfonamides) were determined in
      wastewater and sludge samples originating from two different wastewater treatment
      plants (WWTPs). The analytes were extracted by solid phase extraction (dissolved
      phase) or sonication followed by solid phase extraction (solid phase).
      Qualitative and quantitative analyses were performed by LC-MS/MS. According to
      the results, perfluoropentanoic acid (PFPeA), perfluorooctanoic acid (PFOA) and
      perfluorooctane sulfonate (PFOS) were dominant in wastewater and sludge samples
      from both plants. The average concentrations in the raw and treated wastewater
      ranged up to 75.7 ng L(-1) (perfluorotridecanoic acid, PFTrDA) and 76.0 ng L(-1)
      (PFPeA), respectively. Concentrations of most PFCs were higher in effluents than
      in influents, indicating their formation during wastewater treatment processes.
      In sewage sludge, the average concentrations ranged up to 6.7 ng g(-1) dry weight
      (PFOS). No significant seasonal variations in PFCs concentrations were observed,
      while higher concentrations of PFOA, PFOS and perfluorononanoic acid (PFNA) were
      determined in the WWTP receiving municipal and industrial wastewater.
      Significantly different distribution coefficient (Kd) values were determined for
      different PFCs and different type of sludge, ranging between 169 L kg(-1) (PFHxS)
      to 12,922 L kg(-1) (PFDA).

PMID- 22370205
TI  - Microbial degradation of 4-monobrominated diphenyl ether with anaerobic sludge.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant additives
      for many plastic and electronic products. Owing to their ubiquitous distribution
      in the environment, multiple toxicity to humans, and increasing accumulation in
      the environment, the fate of PBDEs is of serious concern for public safety. In
      this study, the degradation of 4-monobrominated diphenyl ether (BDE-3) in
      anaerobic sludge and the effect of carbon source addition were investigated. BDE
      3 can be degraded by two different anaerobic sludge samples. The by-products,
      diphenyl ether (DE) and bromide ions, were monitored, indicating the reaction of
      debromination within these anaerobic samples. Co-metabolism with glucose
      facilitated BDE-3 biodegradation in terms of kinetics and efficiency in the
      Jhongsing sludge. Through the pattern of amplified 16S rRNA gene fragments in
      denatured gradient gel electrophoresis (DGGE), the composition of the microbial
      community was analyzed. Most of the predominant microbes were novel species. The
      fragments enriched in BDE-3-degrading anaerobic sludge samples are presumably
      Clostridium sp. This enrichment coincides with the H(2) gas generation and the
      facilitation of debromination during the degradation process. Findings of this
      study provide better understanding of the biodegradation of brominated DEs and
      can facilitate the prediction of the fate of PBDEs in the environment.

PMID- 22370206
TI  - Thoracic nerve root hemangioblastoma--a diagnostic rarity.

PMID- 22370207
TI  - Arteriovenous malformation-associated intracerebral hemorrhage.

PMID- 22370208
TI  - Surgical intervention for cerebral ischemia: effective or not?

PMID- 22370209
TI  - Anorectal lesion in a middle-aged woman.

PMID- 22370210
TI  - An unusual cause of abdominal distention and acute dyspnea.

PMID- 22370211
TI  - Albumin regeneration for extracorporeal liver support using prometheus: a step in
      the right direction.

PMID- 22370212
TI  - An unusual cause of recurrent acute abdominal pain.

PMID- 22370213
TI  - Ingested magnets: catch or let go?

PMID- 22370214
TI  - An unusual submucosal tumor of the stomach.

PMID- 22370215
TI  - A case of obscure gastrointestinal bleeding.

PMID- 22370216
TI  - What is this in the orifice of the appendix vermiformis?

PMID- 22370217
TI  - Gastrointestinal amyloidosis secondary to inherited skin disorder.

PMID- 22370218
TI  - Small, nondescript ulcers with an uncommon etiology.

PMID- 22370219
TI  - Hepatitis B virus, a sex hormone-responsive virus.

PMID- 22370220
TI  - Peripheral human gammadelta T cells control growth of both avirulent and highly
      virulent strains of Francisella tularensis in vitro.
AB  - In this paper we evaluate the role of human gammadelta T cells in control of
      Francisella tularensis infection. Using an in vitro model of infection, a
      reduction in bacterial numbers was detected in the presence of human gammadelta T
      cells for both attenuated LVS and virulent SCHU S4 strains of F. tularensis.
      Antibody neutralisation of IFN-gamma caused an increase in survival of F.
      tularensis LVS suggesting that gammadelta T cell-mediated control of F.
      tularensis infection is partially mediated by IFN-gamma.

PMID- 22370221
TI  - Metabolite profiling reveals novel multi-level cold responses in the diploid
      model Fragaria vesca (woodland strawberry).
AB  - Winter freezing damage is a crucial factor in overwintering crops such as the
      octoploid strawberry (Fragaria * ananassa Duch.) when grown in a perennial
      cultivation system. Our study aimed at assessing metabolic processes and
      regulatory mechanisms in the close-related diploid model woodland strawberry
      (Fragaria vescaL.) during a 10-days cold acclimation experiment. Based on gas
      chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) metabolite profiling
      of three F. vesca genotypes, clear distinctions could be made between leaves and
      non-photosynthesizing roots, underscoring the evolvement of organ-dependent cold
      acclimation strategies. Carbohydrate and amino acid metabolism, photosynthetic
      acclimation, and antioxidant and detoxification systems (ascorbate pathway) were
      strongly affected. Metabolic changes in F. vesca included the strong modulation
      of central metabolism, and induction of osmotically-active sugars (fructose,
      glucose), amino acids (aspartic acid), and amines (putrescine). In contrast, a
      distinct impact on the amino acid proline, known to be cold-induced in other
      plant systems, was conspicuously absent. Levels of galactinol and raffinose, key
      metabolites of the cold-inducible raffinose pathway, were drastically enhanced in
      both leaves and roots throughout the cold acclimation period of 10 days.
      Furthermore, initial freezing tests and multifaceted GC/TOF-MS data processing
      (Venn diagrams, independent component analysis, hierarchical clustering) showed
      that changes in metabolite pools of cold-acclimated F. vesca were clearly
      influenced by genotype.

PMID- 22370222
TI  - The activation, by antigen, of naive TCR transgenic CD4 T cells cultured at
      physiological, rather than artificially high, frequencies more accurately
      reflects the in vivo activation of normal numbers of naive CD4(+) T cells.
AB  - The majority of in vitro studies investigating the activation of naive TCR
      transgenic T cells routinely employ an artificially high frequency of such cells.
      To assess whether employing high frequencies of TCR transgenic cells in vitro
      accurately reflects the in vivo activation of a normal number of T cells, we
      cultured between 300 and 3*10(6) Rag2(-/-) DO11.10 T cells per well under
      otherwise identical conditions. We find that those T cells cultured at low
      frequencies proliferate more and are more potently activated, as assessed by the
      expression of CD44 and CD62L, each giving rise to a much larger number of
      cytokine producing cells, comparable to the number generated in vivo when a
      normal number of CD4(+) T cells are activated. The effect of T cell frequency on
      the level of their activation was not due to differences in MHCII or CD80/86
      expression by B cells, the major APC population present, nor to increased death
      of B cells in high frequency cultures. Taken together, our observations
      illustrate the necessity of culturing naive TCR transgenic CD4(+) T cells at a
      physiological frequency if one is to more accurately recapitulate the in vivo
      activation of naive CD4(+) T cells.

PMID- 22370223
TI  - Geographical distribution modelling for Neospora caninum and Coxiella burnetii
      infections in dairy cattle farms in northeastern Spain.
AB  - Maximum entropy ecological niche modelling and spatial scan statistic were
      utilized to predict the geographical range and to investigate clusters of
      infections for Neospora caninum and Coxiella burnetii in dairy cattle farms in
      Catalonia, northeastern Spain, using the Maxent and SaTScan programs,
      respectively. The geographical distribution of Neospora and Coxiella with the
      highest level of probability (P > 0.60) covers central Catalonia and spreads
      towards northeastern Catalonia which contains a high concentration of dairy
      cattle farms. The most important environmental factor that contributed to the
      ecological niche modelling was precipitation of driest month followed by
      elevation. Significant clusters (P < 0.001) were detected for Neospora and
      Coxiella infections in the western and eastern regions of Catalonia,
      respectively.

PMID- 22370224
TI  - [The pharmacological treatment of obesity: past, present and future].
AB  - Currently, obesity presents one of the biggest health problems. Management
      strategies for weight reduction in obese individuals include changes in life
      style such as exercise and diet, behavioral therapy, and pharmacological
      treatment, and in certain cases surgical intervention. Diet and exercise are best
      for both prevention and treatment, but both require much discipline and are
      difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it
      may only have modest results, limited by side effects; furthermore, the weight
      lowering effects last only as long as the drug is being taken and, unfortunately,
      as soon as the administration is stopped, the weight is regained. These
      strategies should be used in a combination for higher efficacy. Drugs used to
      induce weight loss have various effects: they increase satiety, reduce the
      absorption of nutrients or make metabolism faster; but their effect is usually
      moderate. In the past, several drugs were used in the pharmacological therapy of
      weight reduction including thyroid hormone, dinitrophenol, amphetamines and their
      analogues, e.g. fenfluramine, At present, only orlistat is available in the long
      term treatment (>= 24 weeks) of obesity as sibutramine and rimonabant were
      withdrawn form the market. Several new anti-obesity drugs are being tested at
      present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most
      promising one.

PMID- 22370225
TI  - [Hungarian consensus guideline for the diagnosis and treatment of B, C, and D
      viral hepatitis].
AB  - More than 1% of the Hungarian population is infected with hepatitis B, C, or D
      viruses. Since 2006 the diagnostics and therapy of these infections are carried
      out in treatment centers according to national guidelines - since 2010 according
      to financial protocols. The consensus-based guidelines for 2012 are published in
      this paper. The guidelines stress the importance of quick and detailed virologic
      evaluations, the applicability of transient elastography as an acceptable
      alternative of liver biopsy in this regard, as well as the relevance of
      appropriate consistent follow up schedule for viral response during therapy. The
      first choice of therapy in chronic hepatitis B infection is pegylated interferon
      for 48 weeks or continuous entecavir therapy. The later must be continued for at
      least 6 months after hepatitis B surface antigen (HBsAg) seroconversion.
      Tenofovir disoproxil fumarat is not yet reimbursed by the National Health
      Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy.
      Lamivudine is no longer a first choice; patients currently taking lamivudine must
      switch if response is inadequate. Appropriate treatment of patients taking
      immunosuppressive medications is highly recommended. Pegylated interferon based
      therapy is recommended for the treatment of concomitant hepatitis D infection.
      Treatment naive chronic hepatitis C patients should initially receive pegylated
      interferon and ribavirin dual combination therapy. In genotype 1 infection if
      response is insufficient at 4 or 12 weeks one of the two new direct acting
      antivirals (boceprevir or telaprevir) should be added. The length of treatment is
      usually 48 weeks; in cases of extended early viral response shorter courses are
      recommended. Previous treatment failure patients with genotype 1 infection should
      receive a protease inhibitor backed triple combination therapy, mostly for 48
      weeks. However, relapsers without cirrhosis and with extended rapid viral
      response, shorter telaprevir based combination therapy is sufficient. Drug-drug
      interactions as well as emergence of viral resistance are of particular
      importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4
      infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is
      recommended in general. The guidelines published here become protocols when
      published as official publications of the Hungarian Health Authority.

PMID- 22370226
TI  - [Dr. Emil Dillnberger (1832-1882), a forgotten author of 19th-century medical
      dissertations highly esteemed even outside Europe].

PMID- 22370228
TI  - The application of graphene as electrodes in electrical and optical devices.
AB  - Graphene is a promising next-generation conducting material with the potential to
      replace traditional electrode materials such as indium tin oxide in electrical
      and optical devices. It combines several advantageous characteristics including
      low sheet resistance, high optical transparency and excellent mechanical
      properties. Recent research has coincided with increased interest in the
      application of graphene as an electrode material in transistors, light-emitting
      diodes, solar cells and flexible devices. However, for more practical
      applications, the performance of devices should be further improved by the
      engineering of graphene films, such as through their synthesis, transfer and
      doping. This article reviews several applications of graphene films as electrodes
      in electrical and optical devices and discusses the essential requirements for
      applications of graphene films as electrodes.

PMID- 22370229
TI  - Development of a calibration protocol and identification of the most sensitive
      parameters for the particulate biofilm models used in biological wastewater
      treatment.
AB  - Biofilm models are valuable tools for process engineers to simulate biological
      wastewater treatment. In order to enhance the use of biofilm models implemented
      in contemporary simulation software, model calibration is both necessary and
      helpful. The aim of this work was to develop a calibration protocol of the
      particulate biofilm model with a help of the sensitivity analysis of the most
      important parameters in the biofilm model implemented in BioWin(r) and verify the
      predictability of the calibration protocol. A case study of a circulating
      fluidized bed bioreactor (CFBBR) system used for biological nutrient removal
      (BNR) with a fluidized bed respirometric study of the biofilm stoichiometry and
      kinetics was used to verify and validate the proposed calibration protocol.
      Applying the five stages of the biofilm calibration procedures enhanced the
      applicability of BioWin(r), which was capable of predicting most of the
      performance parameters with an average percentage error (APE) of 0-20%.

PMID- 22370230
TI  - The effect of torrefaction on the chemistry of fast-pyrolysis bio-oil.
AB  - Fast pyrolysis was performed on torrefied loblolly pine and the collected bio
      oils were analyzed to compare the effect of the torrefaction treatment on their
      quality. The results of the analyses show that bio-oils produced from torrefied
      wood have improved oxygen-to-carbon ratios compared to those from the original
      wood with the penalty of a decrease in bio-oil yield. The extent of this
      improvement depends on the torrefaction severity. Based on the GC/MS analysis of
      the pyrolysis bio-oils, bio-oils produced from torrefied biomass show different
      compositions compared to that from the original wood. Specifically, the former
      becomes more concentrated in pyrolytic lignin with less water content than the
      latter. It was considered that torrefaction could be a potential upgrading method
      to improve the quality of bio-oil, which might be a useful feedstock for phenolic
      based chemicals.

PMID- 22370231
TI  - Activated carbons from KOH-activation of argan (Argania spinosa) seed shells as
      supercapacitor electrodes.
AB  - Activated carbons were prepared by KOH-activation of argan seed shells (ASS). The
      activated carbon with the largest surface area and most developed porosity was
      superficially treated to introduce oxygen and nitrogen functionalities. Activated
      carbons with a surface area of around 2100 m(2)/g were obtained. Electrochemical
      measurements were carried out with a three-electrode cell using 1M H(2)SO(4) as
      electrolyte and Ag/AgCl as reference electrode. The O-rich activated carbon
      showed the lowest capacitance (259 F/g at 125 mA/g) and the lowest capacity
      retention (52% at 1A/g), due to surface carboxyl groups hindering electrolyte
      diffusion into the pores. Conversely, the N-rich activated carbon showed the
      highest capacitance (355 F/g at 125 mA/g) with the highest retention (93% at
      1A/g), due to its well-developed micro-mesoporosity and the pseudocapacitance
      effects of N functionalities. This capacitance performance was among the highest
      reported for other activated carbons from a large variety of biomass precursors.

PMID- 22370232
TI  - Integration of aerobic granular sludge and mesh filter membrane bioreactor for
      cost-effective wastewater treatment.
AB  - Conventional MBR has been mostly based on floc sludge and the use of costly
      microfiltration membranes. Here, a novel aerobic granule (AG)-mesh filter MBR
      (MMBR) process was developed for cost-effective wastewater treatment. During 32
      day continuous operation, a predominance of granules was maintained in the
      system, and good filtration performance was achieved at a low trans-membrane
      pressure (TMP) of below 0.025 m. The granules showed a lower fouling propensity
      than sludge flocs, attributed to the formation of more porous biocake layer at
      mesh surface. A low-flux and low-TMP filtration favored a stable system
      operation. In addition, the reactor had high pollutant removal efficiencies, with
      a 91.4% chemical oxygen demand removal, 95.7% NH(4)(+) removal, and a low
      effluent turbidity of 4.1 NTU at the stable stage. This AG-MMBR process offers a
      promising technology for low-cost and efficient treatment of wastewaters.

PMID- 22370233
TI  - Fermentation of lactose and its constituent sugars by Escherichia coli WDHL:
      impact on hydrogen production.
AB  - Fermentations of lactose, glucose and galactose using Escherichia coli WDHL, a
      hydrogen over producer strain, were performed. With glucose as substrate pyruvate
      was mainly routed to the lactate pathway, resulting in hydrogen production and
      yield of 1037 mL and 0.30 mol H(2)/mol of glucose, respectively. When galactose
      was the substrate, the pyruvate formate lyase pathway was the main route for
      pyruvate and a fermentation yield of 1.12 mol H(2)/mol of galactose and a
      hydrogen production of 2080 mL were obtained. The fermentation of lactose or
      glucose plus galactose showed a similar yield of 1.02 mol H(2)/mol of hexose
      consumed. This work clearly demonstrated that the kinetics of hydrogen and
      metabolites production as well as the hydrogen yield were affected by the type of
      sugar used as substrate as reflected by the deviations from the metabolic
      hydrogen-production pathway.

PMID- 22370235
TI  - Sweet buttermilk intake reduces colonisation and translocation of Listeria
      monocytogenes in rats by inhibiting mucosal pathogen adherence.
AB  - The bovine milk fat globule membrane (MFGM) contains several antimicrobial
      components with proven efficacy in vitro, but in vivo evidence is scarce. The
      present study was performed to determine the efficacy of the bovine MFGM in vivo.
      Rats were fed diets based on bovine skimmed milk powder (low in MFGM) or bovine
      sweet buttermilk powder (high in MFGM). After dietary adaptation, rats were
      orally infected with Salmonella enteritidis or Listeria monocytogenes. Whereas
      sweet buttermilk powder did not protect rats against infection with S.
      enteritidis, it protected against L. monocytogenes, as shown by a lower
      colonisation and translocation of this pathogen. Protection coincided with higher
      listericidal capacity of gastric and caecal contents. The digestion products of
      phosphoglycerides and sphingomyelin are bactericidal in vitro. To study their
      role, rats were fed diets containing either 0.1 % phosphatidylcholine or
      sphingomyelin, or a control diet. After dietary adaptation, rats were infected
      with L. monocytogenes. Since Listeria colonisation was not affected by these
      diets, phosphoglycerides and sphingomyelin are not involved in the protective
      effect of sweet buttermilk. Additional in vitro experiments were performed to
      further explore the mechanism of the beneficial effects of sweet buttermilk.
      Inhibition of the adherence of L. monocytogenes to the intestinal mucosa is the
      most likely explanation, since sweet buttermilk powder inhibited the binding of
      L. monocytogenes in both a haemagglutination assay and a Caco-2 cell adherence
      assay. In conclusion, sweet buttermilk powder, which is rich in MFGM, protects
      against L. monocytogenes infection in rats, probably by preventing adherence of
      this pathogen to the intestinal mucosa.

PMID- 22370236
TI  - Effect of caffeic acid phenethyl ester (CAPE) on H2O2 induced oxidative and
      inflammatory responses in human middle ear epithelial cells.
AB  - OBJECTIVE: Acute otitis media (OM) is a common pediatric disease. Recent research
      into the pathogenesis of OM has focused on oxidative damage, induced by oxygen
      free radicals, to the middle ear mucosa along with inflammation. Caffeic acid
      phenethyl ester (CAPE) is a biologically active ingredient of propolis honey
      bees, with antioxidative and anti-inflammatory activities. The effect of CAPE on
      hydrogen peroxide (H(2)O(2))-induced inflammatory and oxidative reactions in the
      middle ear is still not known. The aim of this study was to evaluate the anti
      inflammatory and antioxidative effects of CAPE on cultured human middle ear
      epithelial cells (HMEECs). METHODS: The inflammatory injury of H(2)O(2) and the
      anti-inflammatory effect of CAPE were determined by measuring levels of pro
      inflammatory cytokines (tumor necrosis factor (TNF)-alpha and COX-2) with real
      time reverse transcription polymerase chain reaction and Western blot analysis.
      Oxidative stress induced by H(2)O(2) and antioxidative effects of CAPE were
      evaluated directly by reactive oxygen species (ROS) production using flow
      cytometric analysis of 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein
      diacetate, acetyl ester (CM-H(2)DCFDA), and indirectly by the expression of
      superoxide dismutase (SOD) using Western blot analysis. The effect of CAPE was
      compared with N-acetyl cysteine (NAC) which has well-known antioxidative and anti
      inflammatory effects. RESULTS: CAPE significantly inhibited H(2)O(2)-induced
      upregulation of TNF-alpha and COX-2 expression in a dose and time dependent
      manner. ROS accumulation induced by H(2)O(2) stimulation was decreased by CAPE
      pretreatment. Induced SOD expression after H(2)O(2) stimulation was diminished by
      CAPE pretreatment. The anti-inflammatory and antioxidative effects of CAPE were
      similar to those of NAC. CONCLUSIONS: These findings suggest that inflammation
      induced by H(2)O(2) can be inhibited by CAPE via inhibition of the expression of
      pro-inflammatory cytokines such as TNF-alpha and COX-2. Furthermore, CAPE has
      antioxidative effects, which decreases the need for endogenous SOD expression.

PMID- 22370237
TI  - Complete restoration of auditory impairment in a pediatric case of Cogan's
      syndrome: report of a rare case with long-term follow-up and literature review.
AB  - Cogan's syndrome is characterized by interstitial keratitis, vestibular
      impairment and hearing loss, commonly bilateral. Many patients, especially
      children, experience a delay in proper diagnosis which may delay treatment and
      thus impact on prognosis of hearing restoration. Less than 10 pediatric cases of
      Cogan's syndrome have been reported in literature and only five of them were
      reported with long-term follow-up. We report an extremely rare pediatric case of
      Cogan's syndrome typical form with long-term follow-up and evaluation of hearing
      impairment. Cogan's syndrome must be familiar to otorhinolaryngologists,
      pediatricians and ophthalmologists because early diagnosis and rapid
      administration of the proper therapy increase the probability of recovering
      hearing loss.

PMID- 22370238
TI  - Direct measurement of ear canal volume in a pediatric population: can we explain
      its individual variation in terms of age and body weight?
AB  - OBJECTIVE: The aim of this work was to measure the external auditory canal (EAC)
      volume in children directly and to analyze its variation according to age and
      body weight. METHODS: This was a prospective study at a university-based,
      secondary referral hospital. Volumes of the bony and cartilaginous EACs were
      measured using a 1 ml tuberculin syringe filled with 95% ethyl alcohol before
      inserting ventilation tube(s). Three hundred thirty-eight ears from 194 children
      (107 boys and 87 girls) were enrolled in this study (mean age=58.8 +/- 25.2
      months). They were between the 10th and 90th percentiles for age and gender based
      on the 2007 growth chart for Korean children. RESULTS: EAC volume tended to
      increase with age. The volumes of cartilaginous and total EACs were significantly
      larger in boys than in girls. The volume of the bony EAC was significantly larger
      in right than in left ears. Under the assumption that EAC volume is a linear
      function of age as well as body weight, these factors explained less than one
      third of overall variation. Preferably, the growth of EAC seemed to be not linear
      with aging in pediatric population. CONCLUSIONS: Our cubic model seemed to be
      more fit to the growth of EAC than simple linear model did and age and body
      weight alone were not clinically useful predictors of ear canal volume needed for
      the fitting of hearing aids in pediatric population. Because this variation can
      result in a large variation of real ear to coupler difference (RECD), this study
      supports that individual measurement of the RECD is crucial for fitting
      appropriate hearing aids in children.

PMID- 22370239
TI  - Don't hang your coat here.
AB  - Report 2 cases of coat hanger floor of mouth injuries in children. We describe 2
      cases of children who presented with coat hanger impalement injuries of the floor
      of mouth and their management. Removal under anesthesia is safe with a period of
      observation postoperatively. Impalement injury with coat hangers in the head and
      neck is a rarely encountered or described mechanism of trauma. We report the
      first case series of coat hanger impalement injuries in the floor of mouth in two
      children. Plain film radiographs may be useful to determine the depth of injury
      and trajectory of the foreign body. Careful removal under anesthesia is safe.
      Little if any floor of mouth edema was encountered postoperatively, but close
      observation for potential critical floor of mouth hematoma or edema should be
      considered.

PMID- 22370240
TI  - Post-traumatic morbidity is frequent in children with frontobasilar fractures.
AB  - OBJECTIVE: Frontobasilar fractures are potentially life-threatening injuries also
      in pediatric populations, often due to associated intracranial trauma. This
      retrospective study was performed at a tertiary care university hospital to
      evaluate the management and outcome of pediatric frontobasilar fractures. The
      secondary aim was to re-evaluate the computerized tomography images to reveal all
      the skull base fracture sites predicting morbidity. METHODS: A retrospective
      analysis of all the 20 consecutive pediatric patients diagnosed with and treated
      for a frontobasilar fracture at the Turku University Hospital, Turku, Finland
      during 1995-2010 was performed. The referral area of this tertiary care
      university hospital covers 750,000 inhabitants of whom approximately 20% are 18
      years or younger. RESULTS: The mean annual incidence of frontobasilar fractures
      was 1.1 per 100,000 children aged 18 years and under. A road traffic accident was
      the most common etiological factor. Other factors included being hit by a heavy
      object, falling from a height, and falling to the ground. The mean Glasgow Coma
      Scale score was 10 and loss of consciousness was initially detected in 15 (75%)
      patients in the emergency unit. Twelve (60%) patients had an intracranial injury,
      17 (85%) had facial bone fractures, and 15 (75%) had a fracture of the anterior
      cranial base. The middle cranial fossa and sella were affected in five (25%) of
      the patients. There seem to be no long-term neuroendocrine sequelae following
      brain injury, not even when the sella or the hypophyseal area was affected.
      Twelve (60%) patients were treated operatively. One patient died after one week
      of intensive care treatment. Only four (20%) patients had no post-traumatic
      implications, eight (40%) suffered from various long-term sequelae, and five
      (25%) had permanent neurological or neuropsychological sequelae. CONCLUSIONS:
      Frontobasilar fractures in childhood are rare and often associated with
      intracranial trauma and long-term morbidity. However, according to this study,
      75% of the patients showed no permanent neurological or neuropsychological
      sequelae.

PMID- 22370241
TI  - Cartilage palisade tympanoplasty in children and adults: long term results.
AB  - OBJECTIVE: To show long-term anatomic and functional results of full thickness
      cartilage palisade tympanoplasty in children and adults. METHODS: In 51 patients
      (56 ears); 9 children (12 ears) and 42 adults (44 ears) full thickness cartilage
      palisade tympanoplasty and interposition with malleus head autograft was
      performed. On average 11 years after the tympanoplasty, an otomicroscopy and a
      tonal audiogram were done to assess anatomic and functional results. RESULTS:
      Anatomic results of 56 ears: 40 (71.43%) tympanic membranes have no anatomic
      irregularities; 14 (25.00%) have cartilage resorption (11 of them minor and 3
      major resorptions), 2 (3.57%) have secondary perforation. In the group of
      children all ears tympanic membrane were with no or minor resorption and no
      perforations. Functional results (51 audiograms performed: in children 12 and in
      adults 39): pre- and post-operative average pure tone average air-bone gaps were
      27.29 +/- 10.26 and 10.73 +/- 7.90 dB, respectively. In the group of children pre
      and post-operative average pure tone average air-bone gaps were 29.44 +/- 10.30
      and 6.81 +/- 3.47 dB, respectively. In the group of adults pre- and post
      operative pure tone average air-bone gaps were 26.63 +/- 10.30 and 11.93 +/- 8.50
      dB, respectively. The differences between the two groups preoperatively (z=0.733;
      p=0.463) and postoperatively are irrelevant (z=1.723; p=0.085). The hearing gain
      is bigger in children (F=4.788; p=0.033). CONCLUSION: The full thickness
      cartilage palisade tympanoplasty with malleus autograft interposition is also
      nowadays a successful method in solving of an advanced ear pathology also in
      children.

PMID- 22370242
TI  - Infrared thermal imaging in medicine.
AB  - This review describes the features of modern infrared imaging technology and the
      standardization protocols for thermal imaging in medicine. The technique
      essentially uses naturally emitted infrared radiation from the skin surface.
      Recent studies have investigated the influence of equipment and the methods of
      image recording. The credibility and acceptance of thermal imaging in medicine is
      subject to critical use of the technology and proper understanding of thermal
      physiology. Finally, we review established and evolving medical applications for
      thermal imaging, including inflammatory diseases, complex regional pain syndrome
      and Raynaud's phenomenon. Recent interest in the potential applications for fever
      screening is described, and some other areas of medicine where some research
      papers have included thermal imaging as an assessment modality. In certain
      applications thermal imaging is shown to provide objective measurement of
      temperature changes that are clinically significant.

PMID- 22370244
TI  - Perinatal BPA exposure demasculinizes males in measures of affect but has no
      effect on water maze learning in adulthood.
AB  - Bisphenol A (BPA) is an endocrine disrupting agent that can alter the normal
      gonadal steroid-sensitive sexual differentiation of the brain and behavior. While
      reproductive behavior and physiology are known to be altered by perinatal
      exposure to this compound, less is known about BPA's effects on sex differences
      in learning and measures of affect. In order to evaluate the effects of perinatal
      BPA treatment on learning and affect in adulthood, we exposed rats to one of five
      doses of BPA through gestation and lactation then examined adult behavior in the
      Morris Water Maze (MWM), the Elevated Plus Maze (EPM) and the Forced Swim Test
      (FST). No effect of BPA was observed in the MWM, but on both the EPM and FST, low
      doses (5 MUg/kg) of BPA eliminated sex differences found between controls;
      furthermore, a non-monotonic dose-response observed in previous studies was
      confirmed for these tasks. Overall, our study adds to the growing data suggesting
      that BPA interferes with the normal development of affective behaviors in a non
      linear, dose-dependent manner.

PMID- 22370245
TI  - The profile of executive functioning in amnestic mild cognitive impairment:
      disproportionate deficits in inhibitory control.
AB  - Amnestic mild cognitive impairment (aMCI) represents a group of individuals who
      are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically
      conceptualized as involving predominantly deficits in episodic memory, recent
      studies have demonstrated that deficits in executive functioning may also be
      present, and thorough categorization of cognitive functioning in MCI may improve
      early diagnosis and treatment of AD. We first provide an extensive review of
      neuropsychology studies that examined executive functioning in MCI. We then
      present data on executive functioning across multiple sub-domains (divided
      attention, working memory, inhibitory control, verbal fluency, and planning) in
      40 aMCI patients (single or multiple domain) and 32 normal elderly controls
      (NECs). MCI patients performed significantly worse than NECs in all 5 sub
      domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub
      domains. Impairment on each test was frequent, with 100% of MCI patients
      exhibiting a deficit in at least one sub-domain of executive functioning.
      Inhibitory control was the most frequently and severely impaired. These results
      indicate that executive dysfunction in multiple sub-domains is common in aMCI and
      highlights the importance of a comprehensive neuropsychological evaluation for
      fully characterizing the nature and extent of cognitive deficits in MCI.

PMID- 22370246
TI  - Hyperpnea test triggering malignant ventricular arrhythmia in a child with early
      repolarization.

PMID- 22370243
TI  - Aging-related changes in neuroimmune-endocrine function: implications for
      hippocampal-dependent cognition.
AB  - Healthy aged individuals are more likely to suffer profound memory impairments
      following a challenging life event such as a severe bacterial infection, surgery,
      or an intense psychological stressor, than are younger adults. Importantly, these
      peripheral challenges are capable of producing a neuroinflammatory response,
      (e.g., increased pro-inflammatory cytokines). In this review we will present the
      literature demonstrating that in the healthy aged brain this response is
      exaggerated and prolonged. Normal aging primes or sensitizes microglia and this
      appears to be the source of this amplified response. We will review the growing
      literature suggesting that a dysregulated neuroendocrine response in the aged
      organism is skewed toward higher brain CORT levels, and that this may play a
      critical role in priming microglia. Among the outcomes of an exaggerated
      neuroinflammatory response are impairments in synaptic plasticity, and reductions
      in key downstream mediators such as Arc and BDNF. We will show that each of these
      mechanisms is important for long-term memory formation, and is compromised by
      elevated pro-inflammatory cytokines.

PMID- 22370247
TI  - Genetic variants in SCN5A promoter are associated with arrhythmia phenotype
      severity in patients with heterozygous loss-of-function mutation.
AB  - BACKGROUND: Heterozygous SCN5A mutations have been associated with varied
      arrhythmia phenotypes; phenotype severity may range from asymptomatic
      electrocardiographic changes (mild phenotype) to symptomatic arrhythmias
      resulting in syncope, cardiac arrest, and sudden cardiac death (severe phenotype)
      even among family members carrying the same mutation. Risk-stratification schemes
      for SCN5A mutation carriers remain uncertain. OBJECTIVE: To determine the role of
      SCN5A promoter variants and DNA methylation by using a family-based approach in
      predicting phenotype severity in a kindred with loss-of-function SCN5A mutation.
      METHODS: In a large kindred with a heterozygous SCN5A loss-of-function mutation
      (1936delC, Q646RfsX5; 22 mutation carriers), we sought SCN5A promoter variants.
      In addition, we assessed SCN5A and genome-wide DNA methylation profiles on
      genomic DNA derived from blood (Illumina Human Methylation27 BeadChip). RESULTS:
      During systematic survey of the 2.8-kb SCN5A promoter region, we identified 2
      single nucleotide polymorphisms in complete linkage disequilibrium (rs41310749
      and rs41310239). These promoter variants were significantly associated with
      disease severity (mild vs severe phenotype) (P = .0007), as all 3 patients with
      severe phenotype carried the 2-SNP variant on both mutant and wild-type alleles.
      Analysis did not support a role for the methylation of SCN5A-related genes.
      CONCLUSION: These family-based genetic findings suggest that the presence of
      specific promoter variants increase the risk of a severe phenotype in
      heterozygous carriers of an SCN5A loss-of-function mutation.

PMID- 22370248
TI  - Poor bone health in underprivileged Indian girls: an effect of low bone mass
      accrual during puberty.
AB  - A socio-economic gradient exists for most reasons of morbidity and mortality
      including delayed puberty in lower (LSES) as compared to higher (HSES) socio
      economic stratum and puberty is an important factor affecting bone status in
      children and adolescents. Thus, a cross-sectional study was conducted on 195 age
      matched pairs of girls (8-17years) from LSES and HSES in Pune City, India to
      assess the hypothesis that socio-economic factors working through late puberty
      would have a negative association with bone status of adolescents. Height, weight
      and Tanner stage were assessed. Total body bone mineral content (TBBMC), total
      body bone area (TBBA), total body bone mineral density (TBBMD), lean body mass
      (LBM) and total body fat mass (TBFM) were measured using GE Lunar DPX Pro Pencil
      Beam DXA (Wisconsin, USA) scanner. Mean TBBMC (1172+/-434g), TBBA (1351+/
      356cm(2)), TBBMD (0.846+/-0.104g/cm(2)), LBM (21,622+/-5306g) and TBFM (7746+/
      5194g) in LSES girls were significantly lower than that of HSES girls [TBBMC
      (1483+/-525g), TBBA (1533+/-380cm(2)), TBBMD (0.942+/-0.119g/cm(2)), LBM
      (24,308+/-5829g) and TBFM (12,196+/-7404g)] (p<0.01). There was a significant
      effect of age and puberty on all bone parameters. The differences in TBBMC, TBBA,
      LBM and TBFM between the 2 socio-economic strata at Tanner stage I were not
      significant (p>0.1) whereas there were significant differences in these
      parameters from Tanner stages II to V (p<0.05). The percentage difference between
      LSES and HSES girls in TBBMC, TBBA, TBBMD, LBM and TBFM was 3.4%, 0%, 3.7%, 0.2%
      and 17.3% respectively at Tanner stage I which increased to 19.1%, 9.7%, 10.4%,
      8.8% and 31.2% respectively at Tanner stage V. In conclusion, our results suggest
      that pubertal years may provide a window of opportunity to promote bone health in
      adolescent girls from the lower socio-economic stratum.

PMID- 22370249
TI  - Endovascular treatment of a hepatic artery pseudoaneurysm associated with
      gastrointestinal tract bleeding.
AB  - Hemosuccus pancreaticus is a rare cause of gastrointestinal bleeding from the
      pancreatic duct originating from aneurysms or pseudoaneurysms of peripancreatic
      arteries. It is a life-threatening cause of gastrointestinal bleeding that should
      always be considered in patients with prolonged or intermittent obscure
      gastrointestinal blood loss, or both, especially in patients with pancreatic
      disorders or prior pancreatic surgery. We demonstrate an endovascular treatment
      strategy in a patient with a common hepatic pseudoaneurysm and upper
      gastrointestinal tract bleeding, with preserved flow in the hepatic artery. This
      treatment consisted of a covered stent placement in the hepatic artery, followed
      by transcatheter coil embolization of collateral feeding arteries.

PMID- 22370250
TI  - New pharmacological approaches to atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia facing physicians,
      afflicting 13% of men and 11% of women over 85 years of age. Epidemiological
      studies estimate that there are >= 11 million AF sufferers in the seven major
      economies and that its prevalence will increase two- to threefold over the next
      50 years. Current strategies for treating AF involve either sinus rhythm (SR)
      maintenance or heart rate control, combined with anticoagulation therapy.
      Although SR control is the preferred and most effective treatment of AF, none of
      the SR control drugs currently available are able to maintain rhythm without
      significant side effects. In this article we discuss some of the recent
      advancements in developing new antiarrhythmic drugs for AF.

PMID- 22370251
TI  - Electrospun polyvinyl alcohol-collagen-hydroxyapatite nanofibers: a biomimetic
      extracellular matrix for osteoblastic cells.
AB  - The failure of prosthesis after total joint replacement is due to the lack of
      early implant osseointegration. In this study polyvinyl alcohol-collagen
      hydroxyapatite (PVA-Col-HA) electrospun nanofibrous meshes were fabricated as a
      biomimetic bone-like extracellular matrix for the modification of orthopedic
      prosthetic surfaces. In order to reinforce the PVA nanofibers, HA nanorods and
      Type I collagen were incorporated into the nanofibers. We investigated the
      morphology, biodegradability, mechanical properties and biocompatibility of the
      prepared nanofibers. Our results showed these inorganic-organic blended
      nanofibers to be degradable in vitro. The encapsulated nano-HA and collagen
      interacted with the PVA content, reinforcing the hydrolytic resistance and
      mechanical properties of nanofibers that provided longer lasting stability. The
      encapsulated nano-HA and collagen also enhanced the adhesion and proliferation of
      murine bone cells (MC3T3) in vitro. We propose the PVA-Col-HA nanofibers might be
      promising modifying materials on implant surfaces for orthopedic applications.

PMID- 22370252
TI  - Neuroanatomy of auditory verbal hallucinations in schizophrenia: a quantitative
      meta-analysis of voxel-based morphometry studies.
AB  - INTRODUCTION: Voxel-based morphometry (VBM) studies demonstrate grey matter
      volume (GMV) deficits in schizophrenia. This method is also applied for detecting
      associations between specific psychotic symptoms and brain structure, such as
      auditory verbal hallucinations (AVHs). However, due to differing methodological
      approaches, the available findings are inconsistent and difficult to integrate.
      METHODS: We used a novel voxel-based meta-analytical method to provide a robust
      quantitative review of neuroanatomical abnormalities specifically associated with
      the hallucinatory phenomenon in the schizophrenic brain. We reviewed all VBM
      studies of AVHs in schizophrenia published until July 2011 (n = 9). A total of
      438 patients with a diagnosis of schizophrenia were included (307 with AVHs).
      Using a random-effects parametric voxel-based meta-analysis, coordinates of 83
      foci reported as significant in the source studies were extracted and computed to
      estimate the brain locations most consistently associated with AVHs. RESULTS:
      Severity of AVHs was significantly associated with GMV reductions in the left (p
      = .022) and marginally with the right (p = .062) superior temporal gyri (STGs,
      including Heschl's gyri) across studies examining correlations with AVHs severity
      in patients (n = 8). Analysis of studies categorically comparing patients with
      and without AVHs did not reveal any significant findings, possibly due to the
      small number of studies using this approach (n = 3). CONCLUSIONS: This meta
      analysis implicates bilateral STG (including Heschl's gyri) as key areas of
      structural pathology in AVHs in schizophrenia. These findings support a model
      postulating that aberrations within neural systems involved at different levels
      of language processing are critical to AVHs in schizophrenia.

PMID- 22370253
TI  - Use of theory in low-literacy intervention research from 1980 to 2009.
AB  - OBJECTIVE: To examine whether theories and/or models are used in interventions
      geared towards improving health-related outcomes for individuals with limited
      literacy skills. METHODS: Intervention studies (n=52) published between 1980 and
      2009 that met inclusion criteria  were reviewed to assess the topic addressed,
      type of theory and/or model used, and the extent of theory use. RESULTS: Twenty
      one (40.4%) interventions were based on a theory or model. Most of those 21
      interventions were either "informed by" (n=15, 71.4%) or "applied"  (n=4, 19.1%)
      theory whereas 2 (9.5%) "tested" theory. CONCLUSIONS: Most low-literacy
      intervention research is not based on any educational, behavioral, or social
      science theory or model.

PMID- 22370254
TI  - Barriers to CRC screening among Latino adults in Pennsylvania: ACCN results.
AB  - OBJECTIVES: To describe knowledge of and barriers to colorectal cancer (CRC)
      screening by sex and geography among Latino adults in Pennsylvania. METHODS:
      Eighty-two Latinos >50 years old engaged in one of 8 focus groups. Focus groups
      consisted of 4 components. Focus  group data were audiotaped, transcribed, and
      grouped into thematic units using content analysis. RESULTS: We found significant
      differences in the reported barriers to CRC screenings by sex and geography.
      Identified barriers were placed into 5 domains: (1) physical environment, (2)
      structural,  (3) sociocultural, (4) individual level, and (5) physician related.
      CONCLUSIONS: A targeted approach for CRC screening among Latinos may be better
      than the nontargeted approach.

PMID- 22370256
TI  - Factors associated with physical activity literacy among foster parents.
AB  - OBJECTIVES: To explore associations between physical activity (PA) literacy and
      psychosocial constructs for providing instrumental social support for youth PA.
      METHODS: Ninety-one foster parents completed surveys assessing PA literacy
      (overall and specific), perceptions  of child PA, coordination, PA enjoyment,
      psychosocial variables: positive/negative beliefs, normative beliefs, perceived
      behavioral control (PBC), and self-efficacy. RESULTS: Race, negative beliefs,
      PBC, and foster parent sport involvement were associated with specific PA
      literacy.  Race and education were associated with overall PA literacy.
      CONCLUSIONS: Lower PA literacy is associated with greater negative beliefs and
      lower perceived control suggesting greater perceived barriers and lower perceived
      support for/among African Americans and those with less education.

PMID- 22370255
TI  - Differential accuracy of physical activity self-report by body mass index.
AB  - OBJECTIVES: To examine whether agreement between self-reported and accelerometer
      measured physical activity varies by BMI category in a low-income black sample.
      METHODS: Participants completed a questionnaire and wore an accelerometer for 4-6
      days. Using one- and 10-minute  bouts, accelerometers measured light, moderate,
      and vigorous physical activity time. RESULTS: Correlations varied by obesity
      (nonobese: one-minute r=0.41; 10-minute r=0.47; obese: one-minute r=0.21; 10
      minute r=0 .14). Agreement was highest among nonobese persons (one-minute kappa =
      0.48, 10-minute kappa = 0.023; obese: one-minute kappa = -0.024, 10- minute
      kappa = -0.020). CONCLUSIONS: We found compromised questionnaire performance
      among obese participants.

PMID- 22370257
TI  - Predictors of daily blood glucose monitoring in Appalachian Ohio.
AB  - OBJECTIVE: To determine factors contributing to successful diabetes self
      management in Appalachia, as evidenced by daily blood glucose monitoring.
      METHODS: A telephone survey (N=3841) was conducted to assess health status and
      health care access. The current investigation  is limited to the subset of this
      sample who report having diabetes (N=529). RESULTS: A multivariate logistic
      regression model established that having attended a diabetes education class
      (P<.01) was the most significant predictor of successful diabetes self
      management. The inability  to pay for care, demographic variables, and health
      risk indicators were not found to be significantly related to self-management.
      CONCLUSIONS: This study identifies the role of education in successful diabetes
      self-management for patients in the Appalachian region.

PMID- 22370258
TI  - Preferences, attitudes, and behaviors of health services consumers in Turkey.
AB  - OBJECTIVE: To investigate preferences, attitudes, and behaviors of consumers in
      health care services. METHODS: The study was conducted in the Turkish health care
      context. A total of 810 people who reside in the urban and rural residential
      areas of Ankara were surveyed. RESULTS: The study results suggest that consumer
      attitudes toward health care services differ by the demographic and socio
      cultural characteristics of consumers. CONCLUSIONS: Several managerial
      recommendations pertinent to the analysis of consumer behavior and the
      development  of long-term relationships with consumers were made. Also, future
      research suggestions were provided.

PMID- 22370259
TI  - Tobacco use by college students: a comparison of daily and nondaily smokers.
AB  - OBJECTIVES: To explore demographics, contextual factors, and health risk
      behaviors associated with nondaily smoking by college students. METHODS: In fall
      2005, a random sample of 4100 students completed an online survey. RESULTS: Of
      those surveyed, 29% reported  current smoking; of that 29%, 70% were nondaily
      smokers. Compared to daily smokers, nondaily smokers were younger, African
      American (compared to white), had mothers with higher education, belonged to
      Greek organizations, and attended private (vs public) schools. Nondaily smokers
      were less  likely to have used illicit drugs. CONCLUSIONS: Nondaily and daily
      smokers differed on several demographic and contextual factors, but reported
      mostly similar health risk behaviors.

PMID- 22370260
TI  - Undergraduate physical activity and depressive symptoms: a national study.
AB  - OBJECTIVE: To study the effects of college students' physical activity and gender
      on depressive and suicidal symptoms. METHOD: The National College Health
      Assessment survey was administered to college students nationwide. Data were
      analyzed with 4x2 ANOVAs and Games-Howell  post hoc tests when appropriate.
      RESULTS: More frequent physical activity related to less frequent depressive
      symptoms and consideration of suicide, but not with attempted suicide. Males
      reported depressive symptoms less frequently than did females. CONCLUSION:
      Depression research  has implications for an increasingly sedentary college
      population. Institutions should provide increased access and knowledge pertaining
      to emotional health and psychological benefits through physical activity.

PMID- 22370261
TI  - Longitudinal trajectories of perceived body weight: adolescence to early
      adulthood.
AB  - OBJECTIVE: To examine longitudinal trajectories of perceived weight from
      adolescence to early adulthood by gender. METHODS: We analyzed 9 waves (1997
      2005) of data from the National Longitudinal Survey of Youth (N = 8302) using
      Mplus. RESULTS: Perceived overweight  increased over time among girls and did not
      level off until 23 years of age. Blacks had a lower perceived weight for their
      actual weight and a slower rate of increase in perceived weight than did whites.
      CONCLUSION: Intervention programs designed to prevent or reduce obesity should 
      evaluate weight perceptions for both adolescents and young adults prior to
      implementing each intervention.

PMID- 22370262
TI  - Theory of planned behavior and intention to exercise: effects of setting.
AB  - OBJECTIVES: To explore whether setting type (structured versus unstructured)
      might moderate the relationship between specific theory of planned behavior (TPB)
      constructs and exercise intention. It was hypothesized that perceived behavioral
      control (PBC) would predict intention  only in an unstructured setting. METHODS:
      Students (N=122) completed a questionnaire that assessed TPB constructs and
      exercise intention for a structured (sign up) or unstructured setting (no sign
      up). RESULTS: Simple slopes analysis of the significant interaction revealed PBC 
      was a predictor of intention only in the unstructured setting. CONCLUSIONS: This
      provides support for the suggestion that the effect of PBC on exercise intention
      would be moderated by setting.

PMID- 22370263
TI  - Social cognitive factors associated with physical activity in elementary school
      girls.
AB  - OBJECTIVE: To examine social cognitive factors associated with physical activity
      (PA) among preadolescent girls. METHOD: Social cognitive theory was used to
      examine PA in girls (N=90; 71% African American) participating in Girls on the
      Run. Multiple regressions explored  factors associated with PA at posttesting and
      3-month follow-up. RESULTS: Significant increases in PA, social influences, and
      self-efficacy were found, which were sustained at 3-month follow-up. Self
      efficacy and social influences had the strongest relations to PA at posttest;
      self-efficacy  remained the strongest predictor of PA at 3-month follow-up.
      CONCLUSIONS: Social support and self-efficacy are important targets of PA
      interventions in preadolescent girls.

PMID- 22370264
TI  - Prisoner health and valuation of life, loneliness, and depressed mood.
AB  - OBJECTIVE: To examine valuation of life, loneliness, and depressed mood as
      mediating the association between age and race/ethnicity and health outcomes
      among older adult male prisoners. METHODS: Survey of 261 male prisoners ages 45
      80 from 8 Oklahoma correctional facilities. RESULTS: African American prisoners
      report fewer health conditions than White prisoners - a finding mediated by
      significantly greater valuation of life, less loneliness, and lower depressed
      mood among African American prisoners. Older prisoners reported more health
      conditions  than younger prisoners independent of other study variables.
      CONCLUSION: Results suggest improving inmates' internal states will reduce
      incidence of illness and disease among older male offenders and associated
      healthcare costs.

PMID- 22370265
TI  - Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB2 receptor agonists
      for pain management.
AB  - SAR studies on a series of thiophene amide derivatives provided CB(2) receptor
      agonists. The activity of the compounds was characterized by radioligand binding
      determination, multiple functional assays, ADME, and pharmacokinetic studies. A
      representative compound with selectivity for CB(2) over CB(1) effectively
      produced analgesia in behavioral models of neuropathic, inflammatory, and
      postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the
      efficacy in the pain models resulted from CB(2) agonism.

PMID- 22370266
TI  - Synthesis and evaluation of ursolic acid derivatives as potent cytotoxic agents.
AB  - Structural modification was performed at the C-3 and C-28 positions of ursolic
      acid (UA). Ten UA derivatives with distinct electrical property were synthesized.
      They could be divided into two groups according to their charge under
      physiological conditions: (1) Group I negatively charged and (2) Group II
      positively charged. The anti-proliferative capability of the derivatives was
      evaluated against HepG2, AGS, HT-29 and PC-3 cells by the MTT assay. Flow
      cytometry and Annexin V/PI dual staining assay were carried out to explore the
      antitumor mechanism. The results showed the cytotoxic capacity of the compounds
      was: Group I<UA<Group II. The UA derivatives in Group II exhibited potent
      cytotoxicity and the enhancement of the lipophilicity could further strengthen
      the cytotoxicity. Triggering apoptosis and causing cell cycle arrest contributed
      to the anticancer mechanism. The UA derivative UA-7 had the therapeutic potential
      in the treatment of gastric carcinoma since it showed potent cytotoxicity,
      reasonable oil/water partition, enhanced water solubility, and the ability to
      induce the apoptosis of AGS cells.

PMID- 22370267
TI  - Synthesis and comparative evaluation of 4-oxa- and 4-aza-podophyllotoxins as
      antiproliferative microtubule destabilizing agents.
AB  - A series of novel 4-oxa-podophyllotoxin derivatives 7 featuring the intact
      lactone ring D and various substituents in rings B and E has been synthesized and
      evaluated in a phenotypic sea urchin embryo assay along with the representative 4
      aza-analogs 5 for their antimitotic and microtubule destabilizing activity. The
      most active compounds exhibited myristicin-derived or a 3',5'-dimethoxy
      substitution pattern in the ring E and a 6-methoxy moiety replacing the
      methylenedioxy ring A. Compounds 5xb, 5xe, 5yb, 7xa, 7xb, and 7xc showed potent
      antiproliferative effects in the NCI60 cytotoxicity screen. Notably, growth of
      the multi-drug resistant NCI/ADR-RES cells was more affected by these agents than
      the parent OVCAR-8 cell line. Although generally 4-oxa-podophyllotoxins were less
      potent than the respective 4-aza-derivatives in these assays, stability of the
      former series towards oxidation may prove to be of interest for the development
      of anticancer agents with in vivo activity.

PMID- 22370268
TI  - Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as
      trypanosomal PDE inhibitors. Part 1. Sildenafil analogs.
AB  - Parasitic diseases, such as African sleeping sickness, have a significant impact
      on the health and well-being in the poorest regions of the world. Pragmatic drug
      discovery efforts are needed to find new therapeutic agents. In this Letter we
      describe target repurposing efforts focused on trypanosomal phosphodiesterases.
      We outline the synthesis and biological evaluation of analogs of sildenafil (1),
      a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We
      find that, while low potency analogs can be prepared, this chemical class is a
      sub-optimal starting point for further development of TbrPDE inhibitors.

PMID- 22370269
TI  - Discovery of P2X3 selective antagonists for the treatment of chronic pain.
AB  - Purinergic receptor P2X3 has been linked to analgesia in a number of pre-clinical
      models of pain, and is expressed in the human pain perception pathway. Only few
      P2X3-selective antagonists have been reported to date. This Letter describes the
      SAR and in vivo analgesic profile of a novel scaffold of selective P2X3
      antagonists.

PMID- 22370270
TI  - Novel, druglike 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine-based
      selective inhibitors of human neuronal nitric oxide synthase (nNOS).
AB  - A novel class of 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine
      derivatives was designed, synthesized and evaluated as human nitric oxide
      synthase (NOS) inhibitors. Structure-activity relationship studies based on
      various basic amine side chains attached at the 1-position of the 2,3,4,5
      tetrahydro-1H-benzo[b]azepine ring led to the identification of several potent
      and highly selective inhibitors (17, 18, 25, (+/-)-39, and (+/-)-40) of human
      neuronal NOS. The potential therapeutic application of one of these new selective
      nNOS inhibitors (17) was demonstrated in an in vivo spinal nerve ligation model
      of neuropathic pain, and various in vitro safety pharmacology studies such as the
      hERG K(+) channel inhibition assay and high throughput broad screen (minimal
      activity at 79 receptors/transporters/ion channels).

PMID- 22370271
TI  - Progress for low back pain.

PMID- 22370272
TI  - Biosynthetic approach for functional protein microarrays.
AB  - Protein microarrays have emerged as an indispensable research tool for providing
      information about protein functions and interactions through high-throughput
      screening. Traditional methods for immobilizing biomolecules onto solid surfaces
      have been based on covalent and noncovalent binding, entrapment in semipermeable
      membranes, microencapsulation, sol gel, and hydrogel methods. Each of these
      techniques has its own strengths but fails to combine the most important tenets
      of a functional protein microarray such as covalent attachment, native protein
      conformation, homogeneity of the protein monolayer, control over active site
      orientation, and retention of protein activity. Here we present a selective and
      site-directed covalent immobilization technique for proteins via a benzoxazine
      ring formation through a Diels-Alder reaction in water and a genetically encoded
      3-amino-L-tyrosine (3-NH(2)Tyr) amino acid. Fully functional protein microarrays,
      with monolayer arrangements and complete control over their orientations, were
      generated using this strategy.

PMID- 22370273
TI  - Perfusion reversed-phase high-performance liquid chromatography for protein
      separation from detergent-containing solutions: an alternative to gel-based
      approaches.
AB  - Detergents are frequently used for the solubilization of membrane proteins during
      and after purification steps. Unfortunately some of these detergents impair
      chromatographic separations and mass spectrometry (MS) analysis. Perfusion
      reversed-phase high-performance liquid chromatography (RP-HPLC) using POROS
      materials is suited for separating intact proteins solubilized by detergents due
      to the particles' highly diffusive pores and chemical stability. In this article,
      the use of perfusive reversed-phase material packed into small inner diameter
      capillary columns is presented as a cheap, rapid, and efficient method for the
      removal of different types of detergents from protein solutions. The ability to
      purify and separate the subunits of membrane protein complexes with self-packed
      capillary columns is exemplified for bovine cytochrome bc(1) complex. Even highly
      hydrophobic subunits can be detected in collected fractions by intact mass
      measurements and identified after proteolytic digestion and matrix-assisted laser
      desorption/ionization tandem MS (MALDI MS/MS). The comparison with a gel-based
      approach shows that this method is a valuable alternative for purification and
      separation of intact proteins with subsequent MS analysis and that hydrophobic
      proteins are even better represented in the LC-based approach.

PMID- 22370274
TI  - Palytoxin detection and quantification using the fluorescence polarization
      technique.
AB  - Palytoxin (PLT) is a highly toxic nonpeptidic marine natural product, with a
      complex chemical structure. Its mechanism of action targets Na,K-ATPase.
      Fluorescence polarization (FP) is a spectroscopic technique that can be used to
      determine molecular interactions. It is based on exciting a fluorescent molecule
      with plane-polarized light and measuring the polarization degree of the emitted
      light. In this study, FP was used to develop a detection method based on the
      interaction between the Na,K-ATPase and the PLT. The Na,K-ATPase was labeled with
      a reactive succinimidyl esther of carboxyfluorescein, and the FP of protein-dye
      conjugate was measured when the amount of PLT in the medium was modified. The
      assay protocol was first developed using ouabain as a binding molecule. The final
      result was a straight line that correlates FP units and PLT concentration. Within
      this line the PLT equivalents in a natural sample can be quantified. A selective
      cleaning procedure to mussel samples and dinoflagellates cultures was also
      developed to avoid the matrix effect. The LOQ (limit of quantification) of the
      method is 10nM and the LOD (limit of detection) is 2 nM. This new PLT detection
      method is easier, faster, and more reliable than the other methods described to
      date.

PMID- 22370275
TI  - Uniform aligned bioconjugation of biomolecule motifs for integration within
      microfabricated microfluidic devices.
AB  - Full details and a step-by-step guide suitable for printing proteins aligned to
      micron-sized sensors and subsequent integration and alignment of microfluidic
      structures are presented. The precise alignment and grafting of micron-sized
      biomolecule patterns with an underlying substrate at predefined locations is
      achieved using a novel semi-automated microcontact printer. Through integration
      of optical alignment methods in the x, y, and z directions, uniform contact of
      micron-sized stamps is achieved. Feature compression of the stamp is avoided by
      fine control of the stamp during contact. This printing method has been developed
      in combination with robust, compatible bioconjugate chemistry for patterning of a
      dextran-functionalized silicon oxide substrate with a NeutrAvidin-"inked" stamp
      and subsequent incubation with a biotin-functionalized protein. The bioconjugate
      chemistry is such that uniform coverage of the protein (without denaturation)
      over the printed motif is obtained and reproduction of the initial mask shape and
      dimensions is achieved. Later integration with a microfluidic structure aligned
      with the printed motif on the substrate is also described.

PMID- 22370276
TI  - Capillary electrochromatography and quartz crystal microbalance, valuable
      techniques in the study of heparin-lipoprotein interactions.
AB  - Atherosclerosis is initiated when lipoproteins bind to proteoglycans (PGs) in
      arterial walls. The binding is mediated by apolipoprotein apoB-100 and/or apoE,
      both of which have binding affinity toward heparin. We developed covalently bound
      heparin coatings for APTES-modified silica capillaries and SiO(2) chips and
      carried out capillary electrochromatography (CEC) and quartz crystal microbalance
      (QCM) studies on the interactions of heparin with selected peptide fragments of
      apoB-100 and apoE and, for CEC, also with low- and high-density lipoproteins (LDL
      and HDL), the latter with and without apoE. The peptides are known to mediate
      interactions of HDL and LDL with arterial PGs. Interactions and affinities were
      expressed in CEC as retention factors and reduced mobilities and in continuous
      flow QCM techniques as affinity constants. Both techniques showed heparin
      interactions to be stronger with apoB-100 peptide than with apoE peptide
      fragment, and they confirmed that the sulfate groups in heparin play an
      especially important role in interactions with apoB-100 peptide fragments. In
      addition, CEC confirmed the importance of sulfate groups of heparin in
      interactions between heparin and LDL and between heparin and apoE-containing HDL.
      CEC and QCM acted as excellent platforms to mimic these biologically important
      interactions, with small sample and reagent consumption.

PMID- 22370277
TI  - HWGMWSY, an unanticipated polystyrene binding peptide from random phage display
      libraries.
AB  - Phage display is a powerful technique for the discovery of peptide ligands that
      bind to various targets; however, ambiguous results often appear. Peptide HWGMWSY
      has been isolated repeatedly in our laboratory and by other research groups
      dealing with different protein and nonprotein targets, which led to a hypothesis
      that it may be a target-unrelated peptide interacting with polystyrene plastic
      surfaces. We compared binding properties and amplification rate of phage clone
      displaying the peptide HWGMWSY, a previously confirmed plastic binding clone
      WHWRLPS, and a control phage clone ASVQERK. An enzyme-linked immunosorbent assay
      and a phage elution assay confirmed that phage clone HWGMWSY binds to
      polystyrene. Surface plasmon resonance measurements on the other hand excluded
      the possibility of binding to bovine serum albumin, a common blocking agent in
      phage display experiments. Amplification rates of the above-noted phage clones
      were not statistically different. We therefore conclude that phage clone HWGMWSY
      was isolated in different selection procedures as a result of its affinity to
      polystyrene.

PMID- 22370278
TI  - Removing endotoxin from plasmid samples by Triton X-114 isothermal extraction.
AB  - Triton X-114 temperature transition extraction has been considered to be a simple
      and cost-effective strategy to eliminate endotoxin from plasmid preparations.
      However, a repeated cooling-heating process may promote the degradation of
      plasmid DNA. Based on the finding that the cloud point of Triton X-114 solution
      increases substantially in the presence of small amounts of sodium dodecyl
      sulfate (SDS) and that electrolytes decrease the cloud point of Triton X-114-SDS
      solution drastically, we designed a Triton X-114 isothermal extraction method for
      removing endotoxin from plasmid samples and found that it has the same endotoxin
      removal efficiency when compared with the temperature transition extraction
      method.

PMID- 22370279
TI  - New homogeneous high-throughput assays for inhibitors of beta-catenin/Tcf protein
      protein interactions.
AB  - The transcriptional activator beta-catenin is the primary mediator of the
      canonical Wnt/beta-catenin signaling pathway. The aberrant formation of the beta
      catenin/T-cell factor (Tcf) complex leads to many cancers and organ fibroses.
      Selective inhibition of beta-catenin/Tcf protein-protein interactions represents
      an appealing therapeutic strategy. In this study, two new robust, homogeneous
      high-throughput assays, AlphaScreen and fluorescence polarization, were
      established to study beta-catenin/Tcf interactions. These two new assays
      reproduce native beta-catenin/Tcf interactions, quantify inhibitory potency, and
      are complementary with each other. The establishment of these two high-throughput
      screenings enables quick identification of inhibitors of beta-catenin/Tcf protein
      protein interactions.

PMID- 22370280
TI  - Harnessing aptamers for electrochemical detection of endotoxin.
AB  - Lipopolysaccharide (LPS), also known as endotoxin, triggers a fatal septic shock;
      therefore, fast and accurate detection of LPS from a complex milieu is of primary
      importance. Several LPS affinity binders have been reported so far but few of
      them have proved their efficacy in developing electrochemical sensors capable of
      selectively detecting LPS from crude biological liquors. In this study, we
      identified 10 different single-stranded DNA aptamers showing specific affinity to
      LPS with dissociation constants (K(d)) in the nanomolar range using a NECEEM
      based non-SELEX method. Based on the sequence and secondary structure analysis of
      the LPS binding aptamers, an aptamer exhibiting the highest affinity to LPS
      (i.e., B2) was selected to construct an impedance biosensor on a gold surface.
      The developed electrochemical aptasensor showed excellent sensitivity and
      specificity in the linear detection range from 0.01 to 1 ng/mL of LPS with
      significantly reduced detection time compared with the traditional Limulus
      amoebocyte lysate (LAL) assay.

PMID- 22370281
TI  - Coupling flash liquid chromatography with mass spectrometry for enrichment and
      isolation of milk oligosaccharides for functional studies.
AB  - Mass spectrometry has been coupled with flash liquid chromatography to yield new
      capabilities for isolating nonchromophoric material from complicated biological
      mixtures. A flash liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      method enabled fraction collection of milk oligosaccharides from biological
      mixtures based on composition and structure. The method is compatible with
      traditional gas pressure-driven flow flash chromatography widely employed in
      organic chemistry laboratories. The online mass detector enabled real-time
      optimization of chromatographic parameters to favor separation of
      oligosaccharides that would otherwise be indistinguishable from coeluting
      components with a nonspecific detector. Unlike previously described preparative
      LC/MS techniques, we have employed a dynamic flow connection that permits any
      flow rate from the flash system to be delivered from 1 to 200 ml/min without
      affecting the ionization conditions of the mass spectrometer. A new way of
      packing large amounts of graphitized carbon allowed the enrichment and separation
      of milligram quantities of structurally heterogeneous mixtures of human milk
      oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). Abundant
      saccharide components in milk, such as lactose and lacto-N-tetraose, were
      separated from the rarer and less abundant oligosaccharides that have greater
      structural diversity and biological functionality. Neutral and acidic HMOs and
      BMOs were largely separated and enriched with a dual binary solvent system.

PMID- 22370282
TI  - Characterization of unstable hemoglobin A1c complexes by dynamic capillary
      isoelectric focusing.
AB  - Glucose spontaneously reacts with hemoglobin amino groups to produce unstable
      Schiff base complexes that can dissociate or rearrange to form stable Amadori
      products. We used dynamic capillary isoelectric focusing and boronate affinity
      chromatography to assess the formation and dissociation of unstable hemoglobin
      complexes in vitro. Formation was studied by incubating erythrocytes at 37
      degrees C for up to 24h in phosphate-buffered saline (PBS) supplemented with 0 to
      55.6 mmol/L glucose. Dissociation was studied by incubating glucose-loaded
      erythrocytes in PBS without glucose. Dynamic capillary isoelectric focusing
      separated hemoglobin A1c into two subfractions identified as A1c1 and A1c2. The
      A1c1 subfraction contained both stable and unstable hemoglobin complexes. The
      A1c2 subfraction contained only unstable hemoglobin complexes. Both subfractions
      quantitatively increased in the presence of glucose and decreased in its absence.
      Rates of increase and decrease were faster and time to equilibrium was shorter
      for A1c2 (~4 h) compared with A1c1 (~20 h). Unstable hemoglobin complexes did not
      bind to boronate affinity columns but instead eluted intact in A1c1 and A1c2
      subfractions from nonglycated affinity fractions. Cyanoborohydride reduction
      confirmed the presence of Schiff base complexes. Evidence of multiple unstable
      hemoglobin complexes with different rates of glycation suggests that new models
      are needed to describe nonenzymatic hemoglobin glycation.

PMID- 22370283
TI  - Melatonin utility in neonates and children.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced indoleamine
      secreted by the pineal gland and the secretion is suppressed by light. Melatonin
      is a highly effective antioxidant, free radical scavenger, and has anti
      inflammatory effect. Plenty of evidence supports the utility of melatonin in
      adults for cancer, neurodegenerative disorders, and aging. In children and
      neonates, melatonin has been used widely, including for respiratory distress
      syndrome, bronchopulmonary dysplasia, periventricular leukomalacia (PVL), hypoxia
      ischemia encephalopathy and sepsis. In addition, melatonin can be used in
      childhood sleep and seizure disorders, and in neonates and children receiving
      surgery. This review article discusses the utility of melatonin in neonates and
      children.

PMID- 22370284
TI  - Effect of a 5-HT(1A) receptor agonist (8-OH-DPAT) on the external urethral
      sphincter activity in the rat.
AB  - BACKGROUND/PURPOSE: This study examined the effects of a 5-HT(1A) receptor
      agonist (8-OH-DPAT) on external urethral sphincter (EUS) activity in urethane
      anesthetized rats. METHODS: An EUS electromyogram (EMG) and intravesical pressure
      (IVP) were simultaneously recorded during continuous cystometrographic
      monitoring, to provide a quantitative evaluation of EUS activity and urethral
      urodynamics of voiding. RESULTS: When examining the EUS burst activity, durations
      of the active (AP) and silent periods (SP) as a function of the time axis,
      respectively, exhibited concave- and convex-shaped curves. The burst discharges
      of the EUS-EMG were divided into nonvoiding and voiding burst activities based on
      the oscillation waves of the IVP, which were located in Phases 1 and 2 of the
      IVP. After 8-OH-DPAT treatment, the entire burst period in Phases 1 to 2 of the
      IVP was significantly prolonged. The average SP in both Phases 1 and 2
      significantly increased but the average APs were not affected. Urodynamic results
      showed decreases in the volume threshold, contraction amplitude, and residual
      volume as well as an increase in the contraction duration. In addition, the
      amplitude of bladder high-frequency oscillatory waves in the IVP and the average
      urethral flow rate were reduced, but the entire voiding efficiency increased.
      CONCLUSION: The influences of 8-OH-DPAT on EUS burst activity and urodynamics
      were exactly detected by the sophisticated EMG analytic design, and the results
      could be a reference for the pharmacological treatment of patients with lower
      urinary tract dysfunction.

PMID- 22370285
TI  - Compliance and barriers to implementing the sepsis resuscitation bundle for
      patients developing septic shock in the general medical wards.
AB  - BACKGROUND/PURPOSE: This two-part study aimed to investigate compliance with the
      sepsis resuscitation bundle (SRB) and the barriers to its implementation for
      patients developing septic shock in the general medical wards. METHODS: In the
      first part, medical records of patients who were admitted to the intensive care
      unit from the general medical wards due to septic shock were reviewed. Compliance
      rates with the six SRB components were assessed. In the second part, responsible
      junior physicians (first-year and second-year residents) in the general wards and
      senior physicians (third-year residents and fellows) were randomly invited for
      questionnaire-based interviews. RESULTS: In the first part, during the 6-month
      study period, 40 patients were included. Overall compliance with the SRB within 6
      h was only 2.5%, mainly due to femoral catheterization (42.5%) and the lack of
      measuring central venous oxygen saturation (ScvO2). Delayed completion of SRB
      components contributed little to the low compliance rate. In the second part,
      based on the questionnaire results of 71 junior physicians and 64 senior
      physicians, the junior physicians were less familiar with the SRB guidelines,
      particularly regarding the meaning of ScvO2 (p = 0.01) and management of low
      ScvO2 (p = 0.04). Junior physicians were also more reluctant to measure the
      central venous pressure (CVP; p = 0.04) and the ScvO2 (p = 0.01), and were also
      less confident with internal jugular vein or subclavian vein catheterization (p <
      0.001). CONCLUSION: Compliance with the SRB for patients developing septic shock
      in the general medical wards is very low. Besides providing educational programs
      to improve awareness and acceptance of the SRB, measures to help in central
      venous catheterization and completion of SRB may be considered.

PMID- 22370286
TI  - Viral load and clinical features in children infected with seasonal influenza B
      in 2006/2007.
AB  - BACKGROUND/PURPOSE: In influenza B infection, viral load is believed to be
      related to the severity of clinical illness. The correlation between viral load
      and symptoms is not known. We conducted a study to assess the relationship
      between virus load and clinical features in children infected with influenza B,
      in the hope that clinical features could be used as surrogate markers of viral
      load to guide treatment. METHODS: Between December 2006 and February 2007, 228
      patients with fever and respiratory symptoms were prospectively enrolled in our
      tertiary hospital-based study. Real-time reverse transcription polymerase chain
      reaction (RT-PCR) was performed to determine viral load. RESULTS: Real-time RT
      PCR was positive for influenza B in 76 patients. Using virus culture as the gold
      standard, the sensitivity and specificity were 95% and 87%, respectively.
      Influenza culture positive rate significantly correlated with viral load (p =
      0.03). The median copy number of influenza B virus in the 76 RT-PCR positive
      patients was 9735 copies/ml (range 4.8*101-2.0*106 copies/ml). Samples obtained
      later in the clinical course tended to have lower viral load (p = 0.7), while
      patient age (p = 0.72) and fever duration (p = 0.96) positively related to viral
      load. In patients >3 years of age, myalgia was related to statistically lower
      viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have
      higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended
      to have lower viral loads (1998 vs. 12550; p = 0.06). CONCLUSION: Culture rate
      positively correlated with viral load. Patients with myalgia had a lower viral
      load.

PMID- 22370287
TI  - Suggested cutoff tumor size for management of small EUS-suspected gastric
      gastrointestinal stromal tumors.
AB  - BACKGROUND/PURPOSE: Although the incidence of asymptomatic small gastric
      submucosal tumors increased gradually with routine medical health examination,
      there was little clinical evidence for management consensus in these small
      gastric submucosal tumors including endoscopic ultrasound (EUS)-suspected gastric
      gastrointestinal stromal tumors (GISTs). We investigated the clinical course of
      small EUS-suspected gastric GISTs and propose a cutoff value of tumor size for
      treatment policy. METHODS: In this retrospective study, 50 patients with EUS
      suspected gastric GISTs of sizes less than 3 cm were enrolled and were followed
      up by EUS at least twice over a period of more than 24 months (range 24-101
      months). An at least 20% increase of the maximal diameter of the tumors was set
      as a significant change. RESULTS: Significant changes in tumor size were found
      during the follow-up in 14 patients (28.0%). The one-dimensional 20% change
      corresponded well to 50% change in two-dimensional area measurement (correlation
      coefficient = 0.929). The receiver operating characteristic curve analysis showed
      that the best cutoff size, associated with tumor progression, was 1.4 cm having
      an 85.7% sensitivity, 86.1% specificity, and 86.0% accuracy. A larger tumor size
      (35.7% vs. 2.8%, p = 0.005) and irregular tumor margin on the EUS (71.4% vs. 0, p
      = 0.004) were two significant factors associated with the progression of tumor
      growth of small suspected gastric GISTs. CONCLUSION: Small EUS-suspected GISTs,
      larger than 1.4 cm, with irregular margin were associated with significant
      progression. This subgroup is suggested to be monitored by more intensive follow
      up.

PMID- 22370288
TI  - Otologic and audiologic features of ethnic Chinese patients with Turner syndrome
      in Taiwan.
AB  - BACKGROUND/PURPOSE: Otologic and audiologic characteristics of Turner syndrome
      (TS) have been well documented in Caucasian-but not in Asian-populations. We
      report these features and possible causative factors for hearing loss in ethnic
      Chinese TS patients in Taiwan. METHODS: The study was a cross-sectional trial
      that analyzed patients diagnosed with TS. We enrolled patients for otologic
      evaluations and age-appropriate pure tone audiometry. To explore the potential
      associations with hearing loss, we studied patient karyotype, history of
      recurrent otitis media (OM) and various craniofacial anomalies. RESULTS: The 46
      patients (mean age 17.3 years, range 5-34 years) enrolled, 22 (47.8%) had a
      history of recurrent OM. Otoscopic examination identified eardrum abnormalities
      in 45.6% of patients with myringosclerosis as the most common condition. A total
      of 21.7% patients showed auricular anomalies. Audiologic analysis revealed five
      cases (10.7%) with conductive hearing loss (CHL) and eight cases (17.4%) with
      sensorineural hearing loss (SNHL). Among patients with a history of recurrent OM,
      CHL prevailed (p = 0.0192) over SNHL (p = 0.1278). Karyotype and craniofacial
      anomalies were not associated with CHL or SNHL (p > 0.05). CONCLUSION: We found
      varying degrees of otologic and audiologic abnormalities among the TS in ethnic
      Chinese population. About one-half of the patients had recurrent OM, which was
      more likely to be associated with CHL in early life. Therefore, regular
      surveillance, early diagnosis, and the initiation of appropriate treatment are
      crucial in improving the hearing and speech in children with TS as well as in
      preventing short- and long-term associated complications.

PMID- 22370289
TI  - Combination of nerve blockade and intravenous alfentanil is better than single
      treatment in relieving postoperative pain.
AB  - BACKGROUND/PURPOSE: Multimodal analgesia can improve perioperative analgesia but
      knowledge of combination protocols is still incomplete. This study was designed
      to evaluate whether the combination of sciatic nerve blockade (SNB) and
      intravenous alfentanil (IVA) is more effective than either single treatment in
      relieving postoperative pain in rats. METHODS: In a plantar incision model,
      withdrawal thresholds were evaluated by von Frey test before incision as
      baselines and for 7 days after incision. The animals were randomly allocated into
      various groups to receive SNB with 1% or 2% lidocaine, IVA of 50 or 150 MUg/kg,
      or combined treatments (SNB 1% + 50 MUg/kg IVA or SNB 2% + 150 MUg/kg IVA) before
      incision. The results were compared with those of sham procedures--i.e.,
      injections of peri-sciatic or intravenous saline, or a combination of both.
      RESULTS: Plantar incision caused postoperative allodynia for 3 days. SNB with 2%
      lidocaine reduced allodynia at 1 hour, 3 hours, day 1, and day 2, but not at
      postoperative 5 hours or days 3-7, whereas 150 MUg/kg IVA produced short
      analgesia for only 3 hours after surgery. Neither low-dose SNB nor low-dose IVA
      had a significant effect. When high-dose SNB and high-dose IVA were combined, a
      strong antiallodynic effect was shown in an additive manner. No synergism was
      evidently displayed by the combination. CONCLUSION: Our results indicated that in
      an incisional pain model, multimodal analgesia is superior to single or no
      pretreatment; however, the combination of multimodal analgesic treatments should
      be individually discerned depending on nociceptive types and analgesic
      mechanisms.

PMID- 22370290
TI  - Falsely decreased HbA1c in a type 2 diabetic patient treated with dapsone.
AB  - Glycated hemoglobin A1c (HbA1c) is an important indicator of glycemic control.
      The current recommendation for glycemic control based on HbA1c values has been
      widely accepted. However, HbA1c values depend on the lifespan of erythrocytes and
      the assay methods used. Here, we report the case of a patient with type 2
      diabetes with unusual falling of HbA1c due to interference from dapsone treatment
      for leukocytoclastic vasculitis. He was a 52-year-old man, who was diagnosed with
      type 2 diabetes mellitus 5 years previously and who had been treated in our
      hospital in the past 3 years. Glycemia was controlled by sulfonylurea and
      metformin. During the 3-years follow-up period, HbA1c dropped significantly
      during the addition of dapsone treatment, although plasma glucose levels remained
      stable. HbA1c levels were raised after discontinuation of dapsone. With
      rechallenge of dapsone usage, HbA1c decreased again. We conclude that dapsone may
      be the cause of artificially low HbA1c. Other measurements to monitor glycemic
      control should be considered when dapsone is used for the treatment of concurrent
      disorders, such as autoimmune disease and pneumocystis jiroveci pneumonia.

PMID- 22370291
TI  - Transmission of hepatitis C virus by occupational percutaneous injuries in South
      Korea.
AB  - Korea is an endemic area of hepatitis. Hepatitis C virus (HCV) infections caused
      by occupational percutaneous injuries are a serious problem for healthcare
      workers and there has been a gradual increase in the number of HCV infections. We
      therefore determined the transmission rate of HCV after occupational percutaneous
      injury. This was a retrospective cohort study reviewing all occupational blood
      exposure reports made between January 1, 2004, and December 31, 2008, at a
      university-affiliated acute care hospital. Over the 5-year study period, there
      were 1,516 accidents of occupational exposure to blood; of these, 327 (21.6%)
      were to the blood of HCV-infected patients and 3 (0.9%) healthcare workers became
      infected with HCV (95% CI 0.6-8.8). In Korea, although the bloodborne accidents
      leading to exposure to HCV occurred frequently (21.6%), the transmission rate was
      very low (0.92%).

PMID- 22370292
TI  - Circulating EBV DNA and 18F-FDG PET scan in the diagnosis and monitoring of
      nasopharyngeal carcinoma.

PMID- 22370293
TI  - Widespread occurrence of power-law distributions in inter-repeat distances shaped
      by genome dynamics.
AB  - Repetitive DNA sequences derived from transposable elements (TE) are distributed
      in a non-random way, co-clustering with other classes of repeat elements, genes
      and other genomic components. In a previous work we reported power-law-like size
      distributions (linearity in log-log scale) in the spatial arrangement of Alu and
      LINE1 elements in the human genome. Here we investigate the large-scale features
      of the spatial arrangement of all principal classes of TEs in 14 genomes from
      phylogenetically distant organisms by studying the size distribution of inter
      repeat distances. Power-law-like size distributions are found to be widespread,
      extending up to several orders of magnitude. In order to understand the emergence
      of this distributional pattern, we introduce an evolutionary scenario, which
      includes (i) Insertions of DNA segments (e.g., more recent repeats) into the
      considered sequence and (ii) Eliminations of members of the studied TE family. In
      the proposed model we also incorporate the potential for transposition events
      (characteristic of the DNA transposons' life-cycle) and segmental duplications.
      Simulations reproduce the main features of the observed size distributions.
      Furthermore, we investigate the effects of various genomic features on the
      presence and extent of power-law size distributions including TE class and age,
      mode of parental TE transmission, GC content, deletion and recombination rates in
      the studied genomic region, etc. Our observations corroborate the hypothesis that
      insertions of genomic material and eliminations of repeats are at the basis of
      power-laws in inter-repeat distances. The existence of these power-laws could
      facilitate the formation of the recently proposed "fractal globule" for the
      confined chromatin organization.

PMID- 22370294
TI  - The impact of oxytocin on the hemodynamic features of the milk vein in dairy
      cows: a Color Doppler investigation.
AB  - This manuscript investigates, by Color Doppler ultrasonography, the basal
      hemodynamic features of the left cranial epigastric vein (milk vein) of 210
      Holstein-Friesian cows, throughout lactation. Blood velocity, diameter, blood
      flow of the milk vein (before and after milking) and milk production detected in
      cows administered oxytocin were compared with the same parameters found in
      untreated cows. Blood velocity tended to decrease throughout lactation as did
      milk production, whereas both diameters and blood flows tended to increase
      towards the end of the study. All the four parameters showed higher values in the
      treated cows than in the untreated ones. This study provides a detailed picture
      of the hemodynamic features of the milk vein of the dairy cows throughout
      lactation and suggest that oxytocin may exert a vasodilatory effect, in vivo, at
      least on the cranial epigastric vein of the dairy cow.

PMID- 22370295
TI  - Interplay between rumen digestive disorders and diet-induced inflammation in
      dairy cattle.
AB  - In this review, an overview is provided on the current achievements regarding the
      interplay between rumen digestive disorders and diet-induced inflammation in
      dairy cattle. It starts with a review of factors favoring the disturbances in the
      rumen metabolism, which culminate with development of sub-acute rumen acidosis
      (SARA). The latter digestive disorder is often linked to greater metabolic stress
      of gastrointestinal (GI) microbiota and lowered fiber digestion, as well as with
      disruption of the barrier functions of the GI epithelia, which open the route of
      deleterious molecules to translocate from the GI lumen into the portal system. A
      model is suggested to illustrate the mechanisms of the involvement of digestive
      disorders in the disruption of the host's inner homeostasis leading to activation
      of acute phase response (APR). The latter is part of multifaceted innate immune
      and metabolic responses of the host. According to this model, endotoxin, its
      toxicity, and other metabolic compounds of microbial origin are regarded as
      important immunogenic components of GI tract, which when favored by disruption of
      host barriers triggers a systemic APR. Although the activation of an APR is
      viewed as a protective reaction aiming to reestablish the disturbed homeostasis,
      the presence of inflammatory state over long periods might be associated with
      negative consequences for the host. The review concludes that prolonged systemic
      inflammation can: (1) cause significant changes in the energy and lipid
      metabolism in different body tissues, (2) lead to the development of refractory
      states associated with immune suppression and increased susceptibility to various
      diseases, and (3) artificially increase host's requirements in energy and
      nutrients, lowering the efficiency of energy and feed use by the animal. The
      paper emphasizes the critical role that formulation of healthy diets plays for
      curbing down inflammation and enhancing metabolic health of dairy cows.

PMID- 22370296
TI  - [Effect and role of teriparatide in the treatment of osteoporosis].
AB  - Teriparatide, a treatment formula of parathyroid hormone (PTH) , is a powerful
      anabolic agent on bone, improving its mass, geometry and microarchitecture. It
      can decrease the occurrence of fracture in the subjects with increased fracture
      risks. Teriparatide can provide good protection against fracture using as
      monotherapy, and possibly as combination with an antiresorptive agent such as
      zoledronate. Teriparatide should be considered in patients with osteoporosis who
      sustained the reduction of BMD or fracture on established bisphosphonates or
      SERMs. Treatment period of teriparatide is 1.5-2 years and consecutive use of
      antiresorptive agents is greatly recommended to secure long-term protection
      against fracture after teriparatide treatment.

PMID- 22370297
TI  - [Efficacy of teriparatide in treatment of glucocorticoid-induced osteoporosis].
AB  - The skeletal effects of glucocorticoids include both direct and indirect actions
      on bone that result early, transient in bone resorption accompanied by a decrease
      in bone formation, which is maintained for the duration of glucocorticoid
      therapy. Teriparatide exerts anabolic effects on bone, so it is understandable
      why teriparatide is thought to be a rational treatment option. The effects of 36
      months' treatment with teriparatide and alendronate in women and men with
      glucocorticoid-induced osteoporosis were examined in an active-comparator
      randomized, double-blind, controlled trial. This study confirmed the superiority
      of teriparatide over alendronate with respect BMD changes in the spine and hip
      and significantly reduced risk of vertebral fractures in teriparatide-treated
      patients. However, because teriparatide is significantly more expensive than
      bisphosphonates and has not been demonstrated in adequately powered studies to be
      superior in reducing fractures, bisphosphonates remain the first-line treatment
      option for the majority of glucocorticoid-treated patients at increased risk of
      fracture.

PMID- 22370298
TI  - [Mechanisms of bone anabolic action by PTH].
AB  - Many researchers have been investigated the mechanisms of bone anabolic action by
      PTH through various approaches. For example, an increase in the number of
      osteoblasts at early differentiation stage, anti-apoptotic actions, an
      involvement of growth factors, such as insulin-like growth factor (IGF) - I, and
      Runx2 are included in them. Recent accumulating evidence suggest the involvement
      of canonical Wnt-beta-catenin signaling in PTH actions. Recent studies have
      noticed the role of osteocytes in bone anabolic action by PTH, in contrary to the
      previous concept. We recently identified Tmem119 as an osteoblast differentiation
      factor, which is related to increases in Smad3 andbeta-catenin levels by PTH in
      osteoblasts.

PMID- 22370299
TI  - [Update and perspectives of anabolic therapies for osteoporosis].
AB  - Daily subcutaneous self-injection and weekly subcutaneous injection formulas of
      teriparatide are available as anabolic agents in Japan. These injection formulas
      are expected to serve as a new treatment choice for high fracture-risk patients
      with osteoporosis. In addition, studies using new anabolic agents such as PTHrP,
      calcilytics, and Wnt inhibitor antagonists/antibodies are under way to develop
      new anabolic agents. These agents may become new treatment drugs for osteoporotic
      patients especially with low bone turnover.

PMID- 22370300
TI  - [Effect of PTH on bone structural properties].
AB  - Once-daily administration of parathyroid hormone (PTH) causes increased bone
      formation and bone mass. Both the anabolic and resorptive actions can be
      considered in the context of the anabolic window, a period of time during which
      PTH affects bone formation to a greater extent than it stimulates bone
      resorption. PTH appears to increase bone strength by increasing bone volume,
      number and connectivity of bone trabeculae, as well as by transformation from rod
      like structure to plate-like structure. The change of cortical bone strength is
      complicated due to the increase of cortical thickness associated with increase in
      cortical porosity. The combination and sequential therapies with anti-resorptive
      agents are investigating from the view point of the effect of bone quality and
      bone strength.

PMID- 22370301
TI  - [Effects of parathyroid hormone (teriparatide) on bone quality in osteoporosis].
AB  - Parathyroid hormone (PTH) acts as an anabolic agent and is used for the treatment
      for osteoporosis. Daily or once-weekly self-administered subcutaneous injection
      of human PTH (1-34) (teriparatide) increased bone mineral density (BMD) compared
      to a placebo in post-menopausal osteoporotic patients. Recently, data have
      accumulated that collagen cross-link formation in bone affect bone strength. In
      fact, impaired enzymatic cross-linking and/or an increase in non-enzymatic cross
      links, pentosidine, which is a surrogate marker of advanced glycation end
      products (AGEs) , in bone collagen have been proposed as a major cause of bone
      fragility in osteoporosis. We reported that teriparatide improves bone collagen
      cross-link formation, microarchitecture, and bone mass, resulting in the increase
      of bone strength (Saito M : Osteoporos Int 22 : 2373-83, 2011) . In this review,
      we described how teriparatide improve bone collagen cross-link formation and
      mineral qualities.

PMID- 22370302
TI  - [Effects of parathyroid hormone on bone metabolism : differences between
      intermittent and continuous treatment].
AB  - Numerous animal experiments and human studies have shown that intermittent
      injection of parathyroid hormone (PTH) exerts anabolic effects by increasing bone
      mass, whereas continuous PTH treatment decreases the bone mass. Thus, PTH has
      diverse effects on bone metabolism depending on the mode of administration.
      Several reports suggested that the duration of the serum concentration of PTH
      above the baseline level of endogenous PTH is a critical factor in regulating
      such anabolic and catabolic actions on the bone mass. However, the molecular
      mechanism of different PTH actions is not fully understood yet.

PMID- 22370303
TI  - [Anabolic action of PTH under the loading/unloading condition].
AB  - Parathyroid hormone (PTH) is available for the treatment of osteoporosis in
      Japan. PTH is administered subcutaneously daily or weekly. According to the
      results of animal experiments, the anabolic action of PTH on bone depends on
      dosage, condition of loading, and region of bone. Administration of PTH preserved
      trabecular bone formation rate reduced by immobilization or unloading at the same
      level of that under the normal mobilization or loading condition, but at low dose
      did not preserve periosteal bone formation rate reduced by unloading. PTH at high
      dose (40MUg/kg BW) completely preserved trabecular bone volume reduced by
      immobilization in mice. Thus, we consider that PTH could be clinically effective
      for immobilization- and/or unloading-induced bone loss.

PMID- 22370304
TI  - [Biological function of bone cells on the PTH-driven anabolic effect].
AB  - Parathyroid hormone (PTH) -driven anabolism in bone appears to involve the
      osteoblastic activation and the increased population of preosteoblastic lineages.
      Given that the activities of osteoclasts and osteoblasts are intertwined during
      normal bone remodeling, it is plausible that the anabolic action of PTH is either
      directly or indirectly related to the osteoclast. We have recently reported that
      the absence of osteoclasts in c-fos( - / - ) mice might hinder PTH-driven bone
      anabolism, and that osteoclastic presence may be necessary for full osteoblastic
      differentiation and enhanced bone formation seen after intermittent PTH
      administration. Alternatively, it was suggested that PTH administration inhibits
      sclerostin synthesis by osteocytes, thereby allowing for active bone formation.
      Taken together, PTH affects bone cells in a dual pathway - mediating osteoblastic
      (preosteoblastic) activities or osteocytic synthesis of sclerostin -.

PMID- 22370305
TI  - [Parathyroid hormone for disorders of calcium metabolism and metabolic bone
      diseases other than osteoporosis].
AB  - Recombinant human parathyroid hormone (PTH) analogues reduce fractures in
      patients with osteoporosis by enhancing bone formation and improving bone
      quality. Furthermore, many studies have demonstrated the efficacy of these
      analogues in diseases such as PTH-deficient hypoparathyroidism, bisphosphonate
      related osteonecrosis of the jaw and hypophosphatasia. Further studies are needed
      to examine the long-term effects and the safety of these analogues in children
      and cancer patients.

PMID- 22370306
TI  - [Monitoring bone turnover markers during treatment with the anabolic agent
      teriparatide; in particular, treatment using daily and weekly subucutaneous
      injections].
AB  - Teriparatide (recombinant human PTH1-34 daily subcutaneous injection) has been
      approved for osteoporosis at high risk of fracture in many countries including
      Japan. Teriparatide daily injection therapy has been reported to increase BMD,
      improve microarchitecture of bone, and reduce the risk of new vertebral fractures
      and that of non-vertebral fractures. The observed rapid increase in bone
      formation marker and later increase in bone resorption marker has been described
      as a bone anabolic window. The accumulated information using data from global
      clinical trials further tested in the Phase 3 trial of Japanese patients suggests
      that P1NP monitoring may be a useful aid in the management of patients with
      osteoporosis during teriparatide daily injection treatment. Recently once weekly
      subcutaneous injection of teriparatide has been approved in Japan. Weekly
      teriparatide injection treatment has been reported to reduce the risk of new
      vertebral fractures compared with placebo. Regarding bone turnover markers, serum
      osteocalcin increased and urinary NTX decreased during the weekly teriparatide
      treatment.

PMID- 22370307
TI  - [Evidence for osteoporosis treatment using PTH (1-34) daily subcutaneous
      injection].
AB  - PTH (1-34) daily subcutaneous injection is a bone anabolic agent. It has already
      been approved in more than 80 countries over the world (including Europe and
      United States) and in Japan on Jul 2010. The number of patients treated with this
      agent is more than 20 thousand in Japan and about one million over the world. In
      nonclinical studies, teriparatide was shown to have a unique bone formation
      stimulating effect not seen in existing drugs. In domestic and overseas clinical
      studies, teriparatide was shown to have strong effects in increasing BMD,
      promoting remodeling of bone microstructure and suppressing the onset of
      fracture. Furthermore, it can increase BMD through stimulation of bone formation
      regardless of the nature of prior treatment or the presence/absence of responses
      to prior treatment. With these features, teriparatide is expected to serve as a
      first-line drug for management of patients with osteoporosis at high risk for
      fracture.

PMID- 22370308
TI  - [Evidence in the treatment of osteoporosis using weekly teriparatide injections].
AB  - Parathyroid hormone (PTH) has long been of interest due to its stimulatory effect
      on bone formation and its potential for osteoporosis treatment. However,
      accelerated bone resorption associated with increased bone turnover has been
      reported with daily administration of hPTH (1-34) in animal experiments and
      clinical studies. Weekly teriparatide [hPTH (1-34) ] administration was promoted
      in Japan because it did not increase bone resorption. Weekly teriparatide
      administration delivered superior bone mineral density increases and powerful
      fracture prevention efficacy without increasing bone turnover in fracture
      prevention trials and was approved in September 2011. Weekly teriparatide
      administration is thus expected to greatly contribute to the treatment of high
      fracture-risk osteoporotic patients.

PMID- 22370309
TI  - [Combination or sequential treatment using PTH and anti-resorption therapies].
AB  - PTH increases bone formation and has an anabolic effect on bone. Antiresorptive
      drugs such as bishopshonateand selective estrogen receptor modulator (SERM)
      inhibit bone resorption and increase bone mineral density (BMD) . Efficacy of
      combinationtreatment with PTH and antiresorption drugshas been investigated. It
      has been reported that single intravenous infusion of zoledronic acid along with
      daily subcutaneous injection of PTH (1-34) (teriparatide) increases both spine
      and hip BMD. On the other hand, daily oral alendronate and daily PTH (1-84)
      showed no additive effects. Patients who had been treated with antiresorption
      drugs showed somewhat blunt but significant positive response to teriparatide. It
      warrants sequential therapy with teriparatide following antiresorption drugs that
      is common in daily practice of osteoporosis. Since a period of PTH administration
      is limited up to 24 months and bone mineral density starts to decreases shortly
      after discontinuation of PTH, sequential treatment with antiresorptive agents
      following PTH is highly recommended.

PMID- 22370310
TI  - Leishmania donovani HslV does not interact stably with HslU proteins.
AB  - Genes for HslVU-type peptidases are found in bacteria and in a few select
      Eukaryota, among those such important pathogens as Plasmodium spp. and Leishmania
      spp. In this study, we performed replacements of all three HslV/HslU gene
      homologues and found one of those, HslV, to be essential for Leishmania donovani
      viability. The Leishmania HslV gene can also partially relieve the
      thermosensitive phenotype of a combined HslVU/Lon/ClpXP knockout mutant of
      Escherichia coli, indicating a conserved function. However, we found that the
      role and function of the two Leishmania HslU genes has diverged since neither of
      those interacts stably with HslV. The latter forms a dodecameric complex by
      itself and shows a punctate distribution. We conclude that whilst the basic
      function of HslV may be conserved in Leishmania, its organisation and interaction
      with its canonical complex partner HslU is not. Nevertheless, given the absence
      of HslV from the proteome of mammals and its essential role in Leishmania
      viability, HslV is a promising target for intervention.

PMID- 22370311
TI  - On the role of consolidation radiotherapy in advanced-stage Hodgkin's lymphoma.

PMID- 22370312
TI  - Complete response after imatinib mesylate therapy in a patient with well
      differentiated systemic mastocytosis.

PMID- 22370313
TI  - Cost effectiveness of fracture prevention in postmenopausal women who receive
      aromatase inhibitors for early breast cancer.
AB  - PURPOSE: Aromatase inhibitors (AIs) increase the risk of osteoporosis and related
      fractures in postmenopausal women who receive adjuvant AIs for hormone receptor
      (HR) -positive early breast cancer (EBC). We compared the cost effectiveness of
      alternative screening and treatment strategies for fracture prevention. METHODS:
      We developed a Markov state transition model to simulate clinical practice and
      outcomes in a hypothetical cohort of women age 60 years with HR-positive EBC
      starting a 5-year course of AI therapy after primary surgery for breast cancer.
      Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental
      cost-effectiveness ratio (ICER). We compared the following strategies: no
      intervention; one-time bone mineral density (BMD) screening and selective
      bisphosphonate therapy in women with osteoporosis or osteopenia; annual BMD
      screening and selective bisphosphonate therapy in women with osteoporosis or
      osteopenia; and universal bisphosphonate therapy. RESULTS: ICERs for annual BMD
      screening followed by oral bisphosphonates for those with osteoporosis, annual
      BMD screening followed by oral bisphosphonates for those with osteopenia, and
      universal treatment with oral bisphosphonates were $87,300, $129,300, and
      $283,600 per QALY gained, respectively. One-time BMD screening followed by oral
      bisphosphonates for those with osteoporosis or osteopenia was dominated. Our
      results were sensitive to age at the initiation of AI therapy, type of
      bisphosphonates, post-treatment residual effect of bisphosphonates, and a
      potential adjuvant benefit of intravenous bisphosphonates. CONCLUSION: In
      postmenopausal women receiving adjuvant AIs for HR-positive EBC, a policy of
      baseline and annual BMD screening followed by selective treatment with oral
      bisphosphonates for those diagnosed with osteoporosis is a cost-effective use of
      societal resources.

PMID- 22370314
TI  - First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin
      trial in never-smokers with adenocarcinoma of the lung.
AB  - PURPOSE: Gefitinib has shown high response rate and improved progression-free
      survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared
      efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this
      group of patients as first-line therapy. PATIENTS AND METHODS: In this randomized
      phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung
      adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and
      adequate organ function were randomly assigned to receive either gefitinib (250
      mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m(2) on days 1 and 8;
      cisplatin 80 mg/m(2) on day 1 every 3 weeks, for up to nine courses). The primary
      objective was to demonstrate better overall survival (OS) for gefitinib compared
      with GP in chemotherapy-naive NSLAs. RESULTS: Three hundred nine patients were
      analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did
      not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to
      1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS
      rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to
      1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101).
      Myelosuppression, renal insufficiency, and fatigue were more common in the GP
      arm, but skin toxicities and liver dysfunction were more common in the gefitinib
      arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease
      and died. CONCLUSION: Gefitinib failed to demonstrate superior OS compared with
      GP as first-line therapy for NSLAs.

PMID- 22370315
TI  - Neuropsychological performance in survivors of breast cancer more than 20 years
      after adjuvant chemotherapy.
AB  - PURPOSE: Adjuvant chemotherapy for breast cancer can have adverse effects on
      cognition shortly after administration. Whether chemotherapy has any long-term
      effects on cognition is largely unknown, yet it becomes increasingly relevant
      because of the widespread use of chemotherapy for early-stage breast cancer and
      the improved survival. We investigated whether cyclophosphamide, methotrexate,
      and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse
      cognitive performance more than 20 years after treatment. PATIENTS AND METHODS:
      This case-cohort study compared the cognitive performance of patients with breast
      cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles;
      average time since treatment, 21 years; n = 196) to that of a population-based
      sample of women never diagnosed with cancer (n = 1,509). Participants were
      between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant
      endocrine therapy, secondary malignancy, recurrence, and/or metastasis. RESULTS:
      The women exposed to chemotherapy performed significantly worse than the
      reference group on cognitive tests of immediate (P = .015) and delayed verbal
      memory (P = .002), processing speed (P < .001), executive functioning (P = .013),
      and psychomotor speed (P = .001). They experienced fewer symptoms of depression
      (P < .001), yet had significantly more memory complaints on two of three measures
      that could not be explained by cognitive test performance. CONCLUSION: Survivors
      of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago
      perform worse, on average, than random population controls on neuropsychological
      tests. The pattern of cognitive problems is largely similar to that observed in
      patients shortly after cessation of chemotherapy. This study suggests that
      cognitive deficits following breast cancer diagnosis and subsequent CMF
      chemotherapy can be long lasting.

PMID- 22370316
TI  - Use of tanning beds and incidence of skin cancer.
AB  - PURPOSE: We sought to evaluate the risk effect of tanning bed use on skin cancers
      among teenage and young adults. We also expected to determine whether a dose
      response relationship was evident. PATIENTS AND METHODS: We observed 73,494
      female nurses for 20 years (from 1989 to 2009) in a large and well-characterized
      cohort in the United States and investigated whether frequency of tanning bed use
      during high school/college and at ages 25 to 35 years were associated with a risk
      of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We
      used Cox proportional hazards models and carefully adjusted for host risk
      factors, ultraviolet index of residence, and sun exposure behaviors at a young
      age. RESULTS: During follow-up, 5,506 nurses were diagnosed with BCC, 403 with
      SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin
      cancer for an incremental increase in use of tanning beds of four times per year
      during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95%
      CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for
      melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a
      significantly higher risk of BCC for use during high school/college
      (multivariable-adjusted HR for use more than six times per year compared with no
      use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for
      heterogeneity < .001). CONCLUSION: Our data provide evidence for a dose-response
      relationship between tanning bed use and the risk of skin cancers, especially
      BCC, and the association is stronger for patients with a younger age at exposure.

PMID- 22370317
TI  - Opioid prescription after pain assessment: a population-based cohort of elderly
      patients with cancer.
AB  - PURPOSE: The purpose of this study was to measure opioid prescription (OP) rates
      in elderly cancer outpatients around the time of assessment for pain and to
      evaluate factors associated with receiving OPs for those with severe pain.
      PATIENTS AND METHODS: The cross-sectional cohort includes all patients with
      cancer in Ontario older than age 65 years who completed a pain assessment as part
      of a provincial initiative of systematic symptom screening. Patients were
      assigned to mutually exclusive categories by pain score severity: 0, 1 to 3
      (mild), 4 to 6 (moderate), and 7 to 10 (severe). We linked multiple provincial
      health databases to examine the proportion of patients with an OP within 7 days
      after or 30 days before the assessment date. We examined factors associated with
      OPs for patients with pain scores of 7 to 10. RESULTS: The proportion of patients
      with an OP increased as pain score severity increased: 10% of those with no pain,
      24% of those with mild pain, 45% of those with moderate pain, and 67% of those
      with severe pain. More specifically, for those with severe pain, 41% filled an OP
      within 7 days of assessment for pain, and 26% had an OP from the 30 days before
      assessment for pain, leaving 33% without an OP. In multivariable analysis,
      factors associated with OPs are younger age, male sex, comorbid illness, cancer
      type, and assessment at home. CONCLUSION: Despite a generous time window for
      capturing OPs, the proportion of patients without an OP seems high. Further
      knowledge translation is required to maximize the impact of the symptom screening
      initiative in Ontario and to optimize management of cancer-related pain.

PMID- 22370318
TI  - Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer
      after prior therapy with an epidermal growth factor receptor tyrosine kinase
      inhibitor: a randomized, double-blind phase III trial (ZEPHYR).
AB  - PURPOSE: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth
      factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This
      placebo-controlled trial assessed whether vandetanib conferred an overall
      survival benefit in patients with advanced non-small-cell lung cancer (NSCLC)
      after prior treatment with an EGFR tyrosine kinase inhibitor and one or two
      chemotherapy regimens. PATIENTS AND METHODS: Eligible patients were randomly
      assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression
      or unacceptable toxicity. The primary objective was to compare the outcomes
      between the two arms with respect to overall survival. RESULTS: Overall, 924
      patients received vandetanib (n = 617) or placebo (n = 307). No significant
      increase in overall survival was detected in the vandetanib cohort compared with
      placebo (hazard ratio = 0.95; 95.2% CI, 0.81 to 1.11; P = .527); median overall
      survival was 8.5 months versus 7.8 months for vandetanib and placebo patients,
      respectively. Statistically significant advantages favoring vandetanib were
      observed for progression-free survival (hazard ratio = 0.63; P < .001) and
      objective response rate (2.6% v 0.7%; P = .028). Postprogression therapy was
      balanced across the cohorts in both number and type. Adverse events were
      generally consistent with previous NSCLC studies of vandetanib 300 mg; common
      events occurring with a greater frequency in the vandetanib arm versus placebo
      included diarrhea (46% v 11%), rash (42% v 11%), and hypertension (26% v 3%).
      CONCLUSION: The study did not demonstrate an overall survival benefit for
      vandetanib versus placebo. There was a higher incidence of some adverse events
      with vandetanib.

PMID- 22370320
TI  - Screening for osteoporosis in postmenopausal women with breast cancer receiving
      aromatase inhibitors: less is more?

PMID- 22370319
TI  - Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and
      gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial
      cancer without prior systemic therapy: EORTC Intergroup Study 30987.
AB  - PURPOSE: The combination of gemcitabine plus cisplatin (GC) is a standard regimen
      in patients with locally advanced or metastatic urothelial cancer. A phase I/II
      study suggested that a three-drug regimen that included paclitaxel had greater
      antitumor activity and might improve survival. PATIENTS AND METHODS: We conducted
      a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG)
      with GC in patients with locally advanced or metastatic urothelial carcinoma.
      Primary outcome was overall survival (OS). Secondary outcomes were progression
      free survival (PFS), overall response rate, and toxicity. RESULTS: From 2001 to
      2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and
      314 patients were assigned to GC. After a median follow-up of 4.6 years, the
      median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR],
      0.85; P = .075). OS in the subgroup of all eligible patients was significantly
      longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with
      bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P =
      .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both
      treatments were well tolerated, with more thrombocytopenia and bleeding on GC
      than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on
      PCG than GC (13.2% v 4.3%, respectively; P < .001). CONCLUSION: The addition of
      paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit
      that did not reach statistical significance. Novel approaches will be required to
      obtain major improvements in survival of incurable urothelial cancer.

PMID- 22370321
TI  - Progression-free survival: meaningful or simply measurable?

PMID- 22370322
TI  - A cautionary tale: dosing chemotherapy in infants with retinoblastoma.

PMID- 22370323
TI  - Intracranial metastasis from pediatric GI stromal tumor.

PMID- 22370324
TI  - Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations:
      more trouble with phenocopies.

PMID- 22370325
TI  - FACT: an open-label randomized phase III study of fulvestrant and anastrozole in
      combination compared with anastrozole alone as first-line therapy for patients
      with receptor-positive postmenopausal breast cancer.
AB  - PURPOSE: To compare the effect of therapy with anastrozole versus a combination
      of fulvestrant and anastrozole in women in first relapse of endocrine-responsive
      breast cancer. PATIENTS AND METHODS: Postmenopausal women, or premenopausal women
      receiving a gonadotropin-releasing hormone agonist, with estrogen receptor-
      and/or progesterone receptor-positive disease at first relapse after primary
      treatment of localized disease were open-label randomly assigned to a fulvestrant
      loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole
      daily or to 1 mg of anastrozole daily alone. The primary end point was time to
      progression (TTP). RESULTS: In all, 514 women were randomly assigned to
      fulvestrant plus anastrozole (experimental arm; n = 258) or anastrozole (standard
      arm; n = 256). Approximately two thirds had received adjuvant antiestrogens, but
      only eight individuals had received an aromatase inhibitor. Median TTP was 10.8
      and 10.2 months in the experimental versus standard arm, respectively (hazard
      ratio [HR] = 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was
      37.8 and 38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00).
      Incidences of prespecified adverse events (AEs) were similar. Hot flashes were
      more common in the experimental arm: 63 patients (24.6%) versus 35 patients
      (13.8%) in the standard arm (P = .0023). Death owing to AEs was reported in 11
      (4.3%) and five patients (2.0%) in the experimental versus standard arm,
      respectively. CONCLUSION: Fulvestrant (250 mg + LD regimen) in combination with
      anastrozole offered no clinical efficacy advantage over anastrozole monotherapy
      in this population of individuals with a relatively high proportion of previous
      adjuvant antiestrogen exposure.

PMID- 22370326
TI  - Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients
      with high-risk acute lymphoblastic leukemia: associations with long-term
      echocardiographic outcomes.
AB  - PURPOSE: Doxorubicin causes cardiac injury and cardiomyopathy in children with
      acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might
      help individualize treatment by immediately identifying cardiac injury and
      cardiomyopathy. PATIENTS AND METHODS: Children with high-risk ALL were randomly
      assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with
      dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements
      of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain
      natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C
      reactive protein (hsCRP; inflammatory biomarker) were obtained before, during,
      and after treatment. RESULTS: cTnT levels were increased in 12% of children in
      the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before
      treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP
      levels were increased in 89% of children in the doxorubicin group and in 92% of
      children in the doxorubicin-dexrazoxane group before treatment but in only 48%
      and 20%, respectively, after treatment (P = .07). The percentage of children with
      increased hsCRP levels did not differ between groups at any time. In the first 90
      days of treatment, detectable increases in cTnT were associated with abnormally
      reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness
      4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV
      thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01).
      Increases in hsCRP were not associated with any echocardiographic variables.
      CONCLUSION: cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity
      in children with high-risk ALL. Definitive validation studies are required to
      fully establish their range of clinical utility.

PMID- 22370327
TI  - A way forward on the medically appropriate use of white cell growth factors.

PMID- 22370328
TI  - Topography, clinical, and genomic correlates of 5q myeloid malignancies
      revisited.
AB  - PURPOSE: Interstitial deletions of chromosome 5q are common in acute myeloid
      leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the
      pathogenic role of this region in disease phenotype and clonal evolution. The
      higher level of resolution of single-nucleotide polymorphism array (SNP-A)
      karyotyping may be used to find cryptic abnormalities and to precisely define the
      topographic features of the genomic lesions, allowing for more accurate clinical
      correlations. PATIENTS AND METHODS: We analyzed high-density SNP-A karyotyping at
      diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant
      myeloid disorders. results: We identified chromosome 5q deletions in 142 (12%) of
      1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155
      patients. Patients with deletions involving the centromeric and telomeric
      extremes of 5q have a more aggressive disease phenotype and additional
      chromosomal lesions. Lesions not involving the centromeric or telomeric extremes
      of 5q are not exclusive to 5q- syndrome but can be associated with other less
      aggressive forms of MDS. In addition, larger 5q deletions are associated with
      either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a
      deletion involving the centromeric and/or telomeric regions or heterozygous
      mutations in NPM1 or MAML1 located in 5q35 were present. CONCLUSION: Our results
      suggest that the extent of the affected region on 5q determines clinical
      characteristics that can be further modified by heterozygous mutations present in
      the telomeric extreme.

PMID- 22370329
TI  - Carboplatin-associated ototoxicity in children with retinoblastoma.
AB  - PURPOSE: Carboplatin-induced ototoxicity remains poorly defined but is of
      potential great consequence in children with retinoblastoma. We retrospectively
      assessed the incidence of ototoxicity and its risk factors in children with
      retinoblastoma who were treated with carboplatin. PATIENTS AND METHODS: We
      reviewed the audiologic test results of 60 patients with retinoblastoma who
      received front-line treatment with systemic carboplatin and vincristine according
      to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37).
      Ototoxicity was evaluated by three different grading systems. RESULTS: Twelve
      patients (20%) developed ototoxicity at some time after treatment initiation;
      however, ototoxicity resolved in two patients, and thus,10 patients (17%) had
      sustained hearing loss as documented at their most recent audiologic evaluation.
      Nine of these 10 patients had grade 3 or 4 ototoxicity, and nine patients were
      less than 6 months of age at the start of chemotherapy. Age at the start of
      chemotherapy was the only risk factor identified as a significant predictor of
      sustained hearing loss. Younger age was associated with an increased incidence of
      hearing loss. The different ototoxicity grading systems showed good overall
      agreement in the identification of patients with ototoxicity. Agreement was
      greatest between the Brock and Children's Cancer Group systems. CONCLUSION: We
      found that young patients with retinoblastoma who were treated with systemic
      carboplatin had a higher incidence of ototoxicity than previously reported.
      Younger patients (< 6 months of age at the start of treatment) were more likely
      to have ototoxicity than were older patients. Children treated with carboplatin
      should routinely undergo thorough, long-term audiologic monitoring.

PMID- 22370330
TI  - Pilot randomized controlled trial of individual meaning-centered psychotherapy
      for patients with advanced cancer.
AB  - PURPOSE: Spiritual well-being and sense of meaning are important concerns for
      clinicians who care for patients with cancer. We developed Individual Meaning
      Centered Psychotherapy (IMCP) to address the need for brief interventions
      targeting spiritual well-being and meaning for patients with advanced cancer.
      PATIENTS AND METHODS: Patients with stage III or IV cancer (N = 120) were
      randomly assigned to seven sessions of either IMCP or therapeutic massage (TM).
      Patients were assessed before and after completing the intervention and 2 months
      postintervention. Primary outcome measures assessed spiritual well-being and
      quality of life; secondary outcomes included anxiety, depression, hopelessness,
      symptom burden, and symptom-related distress. RESULTS: Of the 120 participants
      randomly assigned, 78 (65%) completed the post-treatment assessment and 67 (56%)
      completed the 2-month follow-up. At the post-treatment assessment, IMCP
      participants demonstrated significantly greater improvement than the control
      condition for the primary outcomes of spiritual well-being (b = 0.39; P <.001,
      including both components of spiritual well-being (sense of meaning: b = 0.34; P
      = .003 and faith: b = 0.42; P = .03), and quality of life (b = 0.76; P = .013).
      Significantly greater improvements for IMCP patients were also observed for the
      secondary outcomes of symptom burden (b = -6.56; P < .001) and symptom-related
      distress (b = -0.47; P < .001) but not for anxiety, depression, or hopelessness.
      At the 2-month follow-up assessment, the improvements observed for the IMCP group
      were no longer significantly greater than those observed for the TM group.
      CONCLUSION: IMCP has clear short-term benefits for spiritual suffering and
      quality of life in patients with advanced cancer. Clinicians working with
      patients who have advanced cancer should consider IMCP as an approach to enhance
      quality of life and spiritual well-being.

PMID- 22370332
TI  - Effect of Fe doping concentration on optical and magnetic properties of ZnO
      nanorods.
AB  - Herein, a facile low temperature, aqueous solution-based chemical method has been
      demonstrated for large-scale fabrication of Fe doped ZnO nanorods (ZnO:Fe) with a
      series percentage of Fe dopant. Interestingly, the SEM results reveal a uniform
      well dispersed synthesis of ZnO:Fe nanorods throughout the substrate. The x-ray
      diffraction result suggests that Fe substitutes Zn in the ZnO matrix and rules
      out the formation of any secondary phase. Selected area electron diffraction
      investigation verifies the single crystal, hexagonal wurtzite structure of the
      ZnO:Fe nanorods. Energy dispersive spectroscopy data confirm Fe doping of the ZnO
      nanorods with a concentration ranging from 0.9 to 2.2 at.%. The photoluminescence
      spectrum reveals a continuous suppression of defect related broad-band emission
      (I(D)/I(UV) = 1-0.11) by increasing the concentration of the dopant ion, which
      produces the quenching of surface defects present in the nanostructures. An
      enhancement in ferromagnetism (M = 0.15 * 10-2-0.24 * 10-1 emu g-1 at 2000 Oe) is
      found in doped ZnO nanorods.

PMID- 22370334
TI  - A commentary on "Hair analysis for biomonitoring of environmental and
      occupational exposure to organic pollutants".

PMID- 22370335
TI  - In vivo particle tracking and photothermal ablation using plasmon-resonant gold
      nanostars.
AB  - Gold nanostars offer unique plasmon properties that efficiently transduce photon
      energy into heat for photothermal therapy. Nanostars, with their small core size
      and multiple long thin branches, exhibit high absorption cross-sections that are
      tunable in the near-infrared region with relatively low scattering effect, making
      them efficient photothermal transducers. Here, we demonstrate particle tracking
      and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer
      cells incubated with bare nanostars, we observed photothermal ablation within 5
      minutes of irradiation (980-nm continuous-wave laser, 15 W/cm2). On a mouse
      injected systemically with PEGylated nanostars for 2 days, extravasation of
      nanostars was observed and localized photothermal ablation was demonstrated on a
      dorsal window chamber within 10 minutes of irradiation (785-nm continuous-wave
      laser, 1.1 W/cm2). These preliminary results of plasmon-enhanced localized
      hyperthermia are encouraging and have illustrated the potential of gold nanostars
      as efficient photothermal agents in cancer therapy. FROM THE CLINICAL EDITOR:
      Gold nanostars are tunable in the near-infrared region with low scattering, thus
      enable photothermal therapy. Encouraging preliminary results of plasmon-enhanced
      localized hyperthermia both in vitro and in vivo demonstrate that Au nanostars
      may be efficient photothermal agents for cancer therapy.

PMID- 22370336
TI  - Multimodality imaging of a right atrial myxoma with pulmonary embolization.

PMID- 22370331
TI  - Dietary fatty acid intake, its food sources and determinants in European
      adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence)
      Study.
AB  - Dietary fatty acids (FA) play a role in several (patho)physiological processes at
      any age, and different FA have different effects on lipid status and health
      outcome. The present study aims to describe the FA intake and its main food
      sources in a population of healthy European adolescents and to assess the
      variation in intake as a function of non-dietary factors. FA intake was assessed
      with 24 h recall interviews in 1804 adolescents aged 12.5-17.5 years. Usual
      intakes were calculated using the multiple source method. Multilevel analyses,
      adjusting for study centre, were used to investigate the influence of non-dietary
      factors. The mean total fat intake was 33.3 (sd 1.2) % of total energy intake
      (%E). The mean SFA intake was 13.8 (sd 1.2) %E, with 99.8 % of the population
      exceeding the recommendations. SFA was mainly delivered by meat and cake, pies
      and biscuits. In most adolescents, the PUFA intake was too low, and 35.5 % of the
      population did not achieve the minimum recommended intake for alpha-linolenic
      acid (ALA). The main determinants of FA intake in the present study population
      were age and sex, as well as physical activity in the male subgroup. No
      contributions of body composition, socio-economic status or sexual maturation to
      the variance in FA intake were observed. In conclusion, the most important public
      health concerns regarding FA intake in this adolescent population were the low
      intake of ALA and the high intake of SFA, mainly seen in the younger-aged boys.
      In this group the major contributor to SFA was meat.

PMID- 22370338
TI  - Design and synthesis of thiourea compounds that inhibit transmembrane anchored
      carbonic anhydrases.
AB  - A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have
      been synthesized from the reaction of glycosyl isothiocyanates with a panel of
      simple benzene sulfonamides comprising either a free amine or hydrazide. All
      compounds were investigated for their ability to inhibit the enzymatic activity
      of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane
      associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar
      thioureido glycoconjugates was high water solubility (> 20 mg/mL), as well many
      of these compounds exhibited a desirable potency and CA isozyme selectivity
      profile. From this library several inhibitors displayed excellent potency
      selectivity profiles for transmembrane anchored CAs over off-target CA I and II.
      These molecules provide potential dual-acting candidates for the development of
      inhibitors that target the extracellular CAs (IX, XII and XIV)-either directly as
      free sugars (membrane impermeable) or indirectly as acetylated prodrugs, becoming
      free sugars upon esterase hydrolysis.

PMID- 22370337
TI  - Intramolecular hydrogen bonding: a potential strategy for more bioavailable
      inhibitors of neuronal nitric oxide synthase.
AB  - Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic
      applications in the treatment of numerous neurodegenerative diseases. Here we
      report the synthesis and evaluation of a series of inhibitors designed to have
      increased cell membrane permeability via intramolecular hydrogen bonding. Their
      potencies were examined in both purified enzyme and cell-based assays; a
      comparison of these results demonstrates that two of the new inhibitors display
      significantly increased membrane permeability over previous analogs. NMR
      spectroscopy provides evidence of intramolecular hydrogen bonding under
      physiological conditions in two of the inhibitors. Crystal structures of the
      inhibitors in the nNOS active site confirm the predicted non-intramolecular
      hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective
      approach for increasing cell membrane permeability without affecting target
      protein binding.

PMID- 22370339
TI  - Synthesis, antimicrobial and anticancer activities of a novel series of diphenyl
      1-(pyridin-3-yl)ethylphosphonates.
AB  - A novel series of diphenyl 1-(arylamino)-1-(pyridin-3-yl)ethylphosphonates 1-5
      was obtained in high yields from reactions of 3-acetyl pyridine with aromatic
      amines and triphenylphosphite in the presence of lithium perchlorate as a
      catalyst. The structures of the synthesized compounds were confirmed by IR, (1)H
      NMR spectral data and microanalyses. Compounds 1-5 showed high antimicrobial
      activities against Escherichia coli (NCIM2065) as a Gram-negative bacterium,
      Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive
      bacteria and Candidaalbicans and Saccharomyces cerevisiae as fungi, at low
      concentrations (10-100 MUg/mL). Also, the synthesized compounds showed
      significant cytotoxicity anticancer activities against liver carcinoma cell line
      (HepG2) and human breast adenocarcinoma cell line (MCF7). The lethal dose of the
      synthesized compounds was also determined and indicated that most compounds are
      safe to use.

PMID- 22370341
TI  - Favourable involvement of alpha2A-adrenoreceptor antagonism in the I2-imidazoline
      binding sites-mediated morphine analgesia enhancement.
AB  - Aim of the present study was to obtain novel alpha(2)-adrenoreceptor (alpha(2)
      AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired
      by the non subtype-selective alpha(2)-AR antagonist idazoxan, we designed 1,4
      dioxane derivatives bearing an aromatic area in position 5 or 6 and the
      imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2,
      with a trans stereochemical relationship between 5-phenyl and 2-imidazoline
      groups, was able to antagonize the sole alpha(2A)-subtype. Moreover, 2 showed an
      affinity at I(2)-imidazoline binding sites (I(2)-IBS) comparable to that at
      alpha(2A)-AR. In in vivo studies 2 strongly increased morphine analgesia. This
      interesting behaviour appeared to be induced by the favourable involvement of
      alpha(2A)-AR antagonism in the I(2)-IBS-mediated morphine analgesia enhancement.

PMID- 22370340
TI  - N4-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d]pyrimidines as potent
      multiple receptor tyrosine kinase inhibitors: design, synthesis, and in vivo
      evaluation.
AB  - With the goal of developing multitargeted receptor tyrosine kinase inhibitors
      that display potent inhibition against PDGFRbeta and VEGFR-2 we designed and
      synthesized eleven N(4)-(3-bromophenyl)-7-(substitutedbenzyl) pyrrolo[2,3
      d]pyrimidines 9a-19a. These compounds were obtained from the key intermediate
      N(4)-(3-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine 29. Various
      arylmethyl groups were regiospecifically attached at the N7 of 29 via sodium
      hydride induced alkylation with substituted arylmethyl halides. Compounds 11a and
      19a were potent dual inhibitors of PDGFRbeta and VEGFR-2. In a COLO-205, in vivo
      tumor mouse model 11a demonstrated inhibition of tumor growth, metastasis, and
      tumor angiogenesis that was better than or comparable to the standard compound
      TSU-68 (SU6668, 8).

PMID- 22370342
TI  - The synthesis of ethacrynic acid thiazole derivatives as glutathione S
      transferase pi inhibitors.
AB  - Glutathione S-transferase pi (GSTpi) is a phase II enzyme which protects cells
      from death and detoxifies chemotherapeutic agents in cancer cells. Ethacrynic
      acid (EA) is a weak GSTpi inhibitor. Structure modifications were done to improve
      the ability of EA to inhibit GSTpi activity. Eighteen EA thiazole derivatives
      were designed and synthesized. Compounds 9a, 9b and 9c with a replacement of
      carboxyl group of EA by a heterocyclic thiazole exhibited improvement over EA to
      inhibit GSTpi activity.

PMID- 22370344
TI  - Characterization of stress responses of heavy metal and metalloid inducible
      promoters in synechocystis PCC6803.
AB  - In several biotechnological applications of living bacterial cells with inducible
      gene expression systems, the extent of overexpression and the specificity to the
      inducer are key elements. In the present study, we established the concentration
      ranges of Zn(2+), Ni(2+), Co(2+), AsO(2)(-), and Cd(2+) ions that caused
      significant activation of the respective promoters of Synechocystis sp. without
      concomitant unspecific stress responses. The low expression levels can be
      increased up to 10-100-fold upon treatments with Cd(2+), AsO(2)(-), Zn(2+), and
      Co(2+) ions and up to 800-fold upon Ni(2+) treatment. These results facilitate
      the development of conditional gene expression systems in cyanobacteria.

PMID- 22370343
TI  - Relative effect of glyphosate on glyphosate-tolerant maize rhizobacterial
      communities is not altered by soil properties.
AB  - The rhizobacterial composition varies according to the soil properties. To test
      if the effect of herbicides on the rhizobacterial communities of genetically
      modified NK603 glyphosate-tolerant maize varies according to different soil
      locations, a comparison was made between the effects of glyphosate (Roundup
      Plus), a post-emergence applied herbicide, and a pre-emergence applied herbicide
      (GTZ) versus untreated soil. The potential effect was monitored by direct
      amplification, cloning, and sequencing of the soil DNA encoding 16S rRNA, and
      high-throughput DNA pyrosequencing of the bacterial DNA coding for the 16S rRNA
      hypervariable V6 region. The results obtained using three different methods to
      analyze the herbicide effect on the rhizobacterial communities of genetically
      modified NK603 maize were comparable to those previously obtained when glyphosate
      tolerant maize was grown in soil with different characteristics. Both herbicides
      decreased the bacterial diversity in the rhizosphere, with Actinobacteria being
      the taxonomic group most affected. The results suggest that both herbicides
      affected the structure of the maize rhizobacterial community, but glyphosate was
      environmentally less aggressive.

PMID- 22370345
TI  - Clostridium difficile toxin A inhibits the kinase activity of extracellular
      signal-related kinases 1 and 2 through direct binding.
AB  - Clostridium difficile toxin A glucosylates Rho family proteins, resulting in
      actin filament disaggregation and cell rounding in cultured colonocytes. Given
      that the cellular toxicity of toxin A is dependent on its receptor binding and
      subsequent entry into the cell, we herein sought to identify additional
      colonocyte proteins that might bind to toxin A following its internalization. Our
      results revealed that toxin A interacted with ERK1 and ERK2 in two human
      colonocyte cell lines (NCM460 and HT29). A GST-pulldown assay also showed that
      toxin A can directly bind to ERK1 and ERK2. In NCM460 cells exposed to PMA (an
      ERK1/2 activator), the phosphorylation of ERK1/2 did not affect the interaction
      between toxin A and ERK1/2. However, an in vitro kinase assay showed that the
      direct binding of toxin A to ERK1 or ERK2 inhibited their kinase activities.
      These results suggest a new molecular mechanism for the cellular toxicity seen in
      cells exposed to toxin A.

PMID- 22370346
TI  - eRF1aMC and Mg(2+) dependent structure switch of GTP binding to eRF3 in Euplotes
      octocarinatus.
AB  - Eukaryotic translation termination is governed by eRF1 and eRF3. eRF1 recognizes
      the stop codons and then hydrolyzes peptidyl-tRNA. eRF3, which facilitates the
      termination process, belongs to the GTPase superfamily. In this study, the effect
      of the MC domain of eRF1a (eRF1aMC) on the GTPase activity of eRF3 was analyzed
      using fluorescence spectra and high-performance liquid chromatography. The
      results indicated eRF1aMC promotes the GTPase activity of eRF3, which is similar
      to the role of eRF1a. Furthermore, the increased affinity of eRF3 for GTP induced
      by eRF1aMC was dependent on the concentration of Mg(2+). Changes in the secondary
      structure of eRF3C after binding GTP/GDP were detected by CD spectroscopy. The
      results revealed changes of conformation during formation of the eRF3C.GTP
      complex that were detected in the presence of eRF1a or eRF1aMC. The conformations
      of the eRF3C.eRF1a.GTP and eRF3C.eRF1aMC.GTP complexes were further altered upon
      the addition of Mg(2+). By contrast, there was no change in the conformation of
      GTP bound to free eRF3C or the eRF3C.eRF1aN complex. These results suggest that
      alterations in the conformation of GTP bound to eRF3 is dependent on eRF1a and
      Mg(2+), whereas the MC domain of eRF1a is responsible for the change in the
      conformation of GTP bound to eRF3 in Euplotes octocarinatus.

PMID- 22370347
TI  - Creation of an ethanol-tolerant yeast strain by genome reconstruction based on
      chromosome splitting technology.
AB  - We sought to breed an industrially useful yeast strain, specifically an ethanol
      tolerant yeast strain that would be optimal for ethanol production, using a novel
      breeding method, called genome reconstruction, based on chromosome splitting
      technology. To induce genome reconstruction, Saccharomyces cerevisiae strain
      SH6310, which contains 31 chromosomes including 12 artificial mini-chromosomes,
      was continuously cultivated in YPD medium containing 6% to 10% ethanol for 33
      days. The 12 mini-chromosomes can be randomly or specifically lost because they
      do not contain any genes that are essential under high-level ethanol conditions.
      The strains selected by inducing genome reconstruction grew about ten times more
      than SH6310 in 8% ethanol. To determine the effect of minichromosome loss on the
      ethanol tolerance phenotype, PCR and Southern hybridization were performed to
      detect the remaining mini-chromosomes. These analyses revealed the loss of mini
      chromosomes no. 11 and no. 12. Mini-chromosome no. 11 contains ten genes
      (YKL225W, PAU16, YKL223W, YKL222C, MCH2, FRE2, COS9, SRY1, JEN1, URA1) and no. 12
      contains fifteen genes (YHL050C, YKL050W-A, YHL049C, YHL048C-A, COS8, YHLComega1,
      ARN2, YHL046W-A, PAU13, YHL045W, YHL044W, ECM34, YHL042W, YHL041W, ARN1). We
      assumed that the loss of these genes resulted in the ethanol-tolerant phenotype
      and expect that this genome reconstruction method will be a feasible new
      alternative for strain improvement.

PMID- 22370348
TI  - Short-hairpin RNA-mediated gene expression interference in Trichoplusia ni cells.
AB  - RNA interference (RNAi) is rapidly becoming a valuable tool in biological
      studies, as it allows the selective and transient knockdown of protein
      expression. The short-interfering RNAs (siRNAs) transiently silence gene
      expression. By contrast, the expressed short-hairpin RNAs induce long-term,
      stable knockdown of their target gene. Trichoplusia ni (T. ni) cells are widely
      used for mammalian cell-derived glycoprotein expression using the baculovirus
      system. However, a suitable shRNA expression system has not been developed yet.
      We investigated the potency of shRNA-mediated gene expression inhibition using
      human and Drosophila U6 promoters in T. ni cells. Luciferase, EGFP, and beta-N
      acetylglucosaminidase (GlcNAcase) were employed as targets to investigate
      knockdown of specific genes in T. ni cells. Introduction of the shRNA expression
      vector under the control of human U6 or Drosophila U6 promoter into T. ni cells
      exhibited the reduced level of luciferase, EGFP, and beta-N-acetylglucosaminidase
      compared with that of untransfected cells. The shRNA was expressed and processed
      to siRNA in our vector-transfected T. ni cells. GlcNAcase mRNA levels were down
      regulated in T. ni cells transfected with shRNA vectors-targeted GlcNAcase as
      compared with the control vector-treated cells. It implied that our shRNA
      expression vectors using human and Drosophila U6 promoters were applied in T. ni
      cells for the specific gene knockdown.

PMID- 22370349
TI  - Optimization of culture medium for novel cell-associated tannase production from
      Bacillus massiliensis using response surface methodology.
AB  - Naturally immobilized tannase (tannin acyl hydrolase, E.C. 3.1.1.20) has many
      advantages, as it avoids the expensive and laborious operation of isolation,
      purification, and immobilization, plus it is highly stable in adverse pH and
      temperature. However, in the case of cell-associated enzymes, since the enzyme is
      associated with the biomass, separation of the pure biomass is necessary.
      However, tannic acid, a known inducer of tannase, forms insoluble complexes with
      media proteins, making it difficult to separate pure biomass. Therefore, this
      study optimizes the production of cell-associated tannase using a "protein-tannin
      complex" free media. An exploratory study was first conducted in shake-flasks to
      select the inducer, carbon source, and nitrogen sources. As a result it was found
      that gallic acid induces tannase synthesis, a tryptose broth gives higher
      biomass, and lactose supplementation is beneficial. The medium was then optimized
      using response surface methodology based on the full factorial central composite
      design in a 3 l bioreactor. A 2(3) factorial design augmented by 7 axial points
      (alpha = 1.682) and 2 replicates at the center point was implemented in 17
      experiments. A mathematical model was also developed to show the effect of each
      medium component and their interactions on the production of cell-associated
      tannase. The validity of the proposed model was verified, and the optimized
      medium was shown to produce maximum cell-associated tannase activity of 9.65 U/l,
      which is 93.8% higher than the activity in the basal medium, after 12 h at pH
      5.0, 30 degrees C. The optimum medium consists of 38 g/l lactose, 50 g/l
      tryptose, and 2.8 g/l gallic acid.

PMID- 22370350
TI  - Laccase- and peroxidase-free tyrosinase production by isolated microbial strain.
AB  - Laccase- and peroxidase-free tyrosinase has commercial importance in the
      production of L-3, 4-dihydroxyphenylalanine (L-DOPA), which is mainly used in the
      treatment of Parkinson's disease. In the present study, isolation of an
      actinomycetes microbial strain capable of producing only tyrosinase is reported.
      Among all soil isolates, three individual colonies revealed black color around
      the colony in the presence of tyrosine. Further screening for laccase and
      peroxidase activities using syringaldazine denoted that one of the isolates,
      designated as RSP-T1, is laccase and peroxidase negative and produces only
      tyrosinase. The microbe was authenticated as Streptomyces antibioticus based on
      16S ribotyping. Effective growth of this isolate was noticed with the use of
      medium (pH 5.5) containing casein acid hydrolysate (10.0 g/l), K(2)HPO(4) (5.0
      g/l), MgSO(4) (0.25 g/l), L-tyrosine (1.0 g/l), and agar (15 g/l). The scanning
      electron micrograph depicted that the microbe is highly branched and filamentous
      in nature. The enzyme production was positively regulated in the presence of
      copper sulfate. The impact of different fermentation parameters on tyrosinase
      production depicted that the maximized enzyme titer values were observed when
      this isolate was grown at 6.5 pH and at 30 degrees C temperature under agitated
      conditions (220 rpm). Among all the studied physiological parameters, agitation
      played a significant role on tyrosinase production. Upon optimization of the
      parameters, the yield of tyrosinase was improved more than 100% compared with the
      initial yield.

PMID- 22370351
TI  - Characterization and fibrinolytic activity of Acetobacter sp. FP1 isolated from
      fermented pine needle extract.
AB  - The strain KCTC 11629BP, isolated from spontaneously fermented pine needle
      extract (FPE), showed fibrinolysis activity. The isolated strain was analyzed in
      physiological and biochemical experiments. Based on 16S rDNA sequencing and
      phylogenic tree analysis, the strain was identified to be a part of the genus
      Acetobacter, with Acetobacter senegalensis and Acetobacter tropicalis as the
      closest phylogenetic neighbors. Based on genotypic and phenotypic results, it was
      proposed that bacterial strain KCTC 11629BP represents a species of the genus
      Acetobacter. The strain was thusly named Acetobacter sp. FP1. In conclusion,
      Acetobacter sp. FP1 isolated from FPE possesses fibrinolytic activity.

PMID- 22370352
TI  - Enhancement of PVA-degrading enzyme production by the application of pH control
      strategy.
AB  - In batch culture for Poly(vinyl alcohol) (PVA)-degrading enzyme (PVAase)
      production by a mixed culture, higher pH (pH 7.5) was favorable for PVAase
      production at the prophase of cultivation, but lower pH (pH 7.0) was favorable at
      the anaphase. This situation was caused by the fact that the optimum pH for
      different key enzymes [PVA dehydrogenase (PVADH) and oxidized PVA hydrolase
      (OPH)] production is various. The activity and average specific production rate
      of PVADH reached the highest values at constant pH 7.5, whereas those of OPH
      appeared at pH 7.0. A two-stage pH control strategy was therefore developed and
      compared for its potential in improving PVAase production. By using this
      strategy, the maximal PVAase activity reached 2.05 U/ml, which increased by 15.2%
      and 24.2% over the fermentation at constant pH 7.5 and 7.0.

PMID- 22370353
TI  - High-efficiency generation of monoclonal antibody for Vitreoscilla hemoglobin
      protein.
AB  - Bacterial hemoglobin from Vitreoscilla (VHb) is recognized as a good fusion
      protein for the soluble expression of foreign protein. In this study, we
      generated a monoclonal antibody (MAb) against VHb for its detection. For the
      rapid screening of MAb, a protein chip technology based on the Alexa-488 (A488)
      dye labeling method was introduced. In order to fabricate the chip, the VHb
      protein was chemically coupled to the chip surface and then the culture
      supernatants of 84 hybridoma cell lines were spotted onto the VHb chip. The bound
      MAbs were measured by A488- modified anti-mouse IgG. A single spot (MAb A10)
      exhibited significantly high signal intensity. The immunoblot analysis evidenced
      that the MAb A10 can detect VHb-fused proteins with high specificity.

PMID- 22370354
TI  - Association of colony morphology with coenzyme Q(10) production and its
      enhancement from Rhizobium radiobacter T6102W by addition of isopentenyl alcohol
      as a precursor.
AB  - Rhizobium radiobacter T6102 was morphologically purified by the aniline blue agar
      plates to give two distinct colonies; white smooth mucoid colony (T6102W) and
      blue rough colony (T6102B). The coenzyme Q(10) (CoQ(10)) was produced just by
      T6102W, showing 2.0 mg/g of CoQ(10) content, whereas the T6102B did not produce
      the CoQ(10). All of the used CoQ(10) biosynthetic precursors enhanced the CoQ(10)
      production by T6102W. Specifically, the supplementation of 0.75 mM isopentenyl
      alcohol improved the CoQ(10) concentration (19.9 mg/l) and content (2.4 mg/g) by
      42% and 40%, respectively.

PMID- 22370355
TI  - Surface display of organophosphorus hydrolase on E. coli using N-terminal domain
      of ice nucleation protein InaV.
AB  - Recombinant Escherichia coli displaying organophosphorus hydrolase (OPH) was used
      to overcome the diffusion barrier limitation of organophosphorus pesticides. A
      new anchor system derived from the N-terminal domain of ice-nucleation protein
      from Pseudomonas syringae InaV (InaV-N) was used to display OPH onto the surface.
      The designed sequence was cloned in the vector pET-28a(+) and then was expressed
      in E. coli. Tracing of the expression location of the recombinant protein using
      SDS-PAGE showed the presentation of OPH by InaV-N on the outer membrane, and the
      ability of recombinant E. coli to utilize diazinon as the sole source of energy,
      without growth inhibition, indicated its significant activity. The location of
      OPH was detected by comparing the activity of the outer membrane fraction with
      the inner membrane and cytoplasm fractions. Studies revealed that recombinant E.
      coli can degrade 50% of 2 mM chlorpyrifos in 2 min. It can be concluded that InaV
      N can be used efficiently to display foreign functional protein, and these
      results highlight the high potential of an engineered bacterium to be used in
      bioremediation of pesticide-contaminated sources in the environment.

PMID- 22370356
TI  - Changes in the activities of enzymes involved in the degradation of butylbenzyl
      phthalate by Pleurotus ostreatus.
AB  - Degradation of butylbenzyl phthalate (BBP) by the white rot fungus Pleurotus
      ostreatus and the activities of some degrading enzymes were examined in two
      different media containing 100 mg/l of the compound. P. ostreatus pregrown for 7
      days in complex YMG medium was able to completely degrade BBP within an
      additional 24 h but degraded only 35 mg/l of BBP in 5 days of incubation in
      minimal medium. Fungal cell mass in the culture in YMG medium was higher in the
      presence than in the absence of BBP. The esterase activity of the fungal culture
      in YMG medium was higher than that in minimal medium and increased with the
      addition of BBP. On the contrary, laccase activity was higher in minimal medium
      and it did not increase upon the addition of BBP. General peroxidase activity
      increased for a few days after the addition of BBP to both media. The degradation
      of BBP and its metabolites by P. ostreatus thus may be attributed mostly to
      esterase rather than lignin-degrading laccase. In addition, the activities of the
      enzymes involved in BBP degradation and their changes varied significantly in the
      different media and culture conditions.

PMID- 22370357
TI  - Bioremediation of Pb-contaminated soil based on microbially induced calcite
      precipitation.
AB  - To remediate lead (Pb)-contaminated soils, it is proposed that microbially
      induced calcite precipitation (MICP) would provide the best alternative to other
      remediation technologies. In this study, Pb bioremediation in soils was
      investigated using the calcite-precipitating bacterium Kocuria flava. Results
      indicate that the Pb is primarily associated with the carbonate fraction in
      bioremediated soil samples. The bioavailability of Pb in contaminated soil was
      reduced so that the potential stress of Pb was alleviated. This research provides
      insight into the geochemistry occurring in the MICP-based Pb-remediated soils,
      which will help in remediation decisions.

PMID- 22370358
TI  - Simultaneous quantification of cyanobacteria and Microcystis spp. using real-time
      PCR.
AB  - In order to develop a protocol to quantify cyanobacteria and Microcystis
      simultaneously, the primers and probe were designed from the conserved regions of
      16S rRNA gene sequences of cyanobacteria and Microcystis, respectively. Probe
      match analysis of the Ribosomal Database Project showed that the primers matched
      with over 97% of cyanobacterial 16S rRNA genes, indicating these can be used to
      amplify cyanobacteria specifically. The TaqMan probe, which is located between
      two primers, matched with 98.2% of sequences in genus GpXI, in which most
      Microcystis strains are included. The numbers of cyanobacterial genes were
      estimated with the emission of SYBR Green from the amplicons with two primers,
      whereas those of Microcystis spp. were measured from the fluorescence of CAL
      Fluor Gold 540 emitted by exonuclease activity of Taq DNA polymerase in
      amplification. It is expected that this method enhances the accuracy and reduces
      the time to count cyanobacteria and potential toxigenic Microcystis spp. in
      aquatic environmental samples.

PMID- 22370359
TI  - Isolation and characterization of Bacillus sp. producing broad-spectrum
      antibiotics against human and plant pathogenic fungi.
AB  - A strain of bacterium producing antifungal antibiotic was isolated and
      identification of the strain was attempted. We could identify the bacterium as
      being a Bacillus sp., based on morphological observation, physiological
      characteristics, and 16S rDNA sequence analysis, thus leading us to designate the
      strain as Bacillus sp. AH-E-1. The strain showed potent antibiotic activity
      against phytopathogenic and human pathogenic fungi by inducing mycelial
      distortion and swelling and inhibiting spore germination. The antibiotic
      metabolite produced by the strain demonstrated excellent thermal and pH (2-11)
      stability, but was labile to autoclaving. From these results, we could find a
      broader antifungal activity of Bacillus genus. Isolation and characterization of
      the active agent produced by the strain are under progress.

PMID- 22370360
TI  - Synthetic Coprisin analog peptide, D-CopA3 has antimicrobial activity and pro
      apoptotic effects in human leukemia cells.
AB  - Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer
      CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin
      like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L
      CopA3) had antibacterial activity and induced apoptosis in human leukemia cells
      via a caspase-independent pathway. In this study, all of amino acid sequences of
      L-CopA3 were modified to all D-form amino acids (D-CopA3) to develop a more
      effective antimicrobial peptide. We investigated whether D-CopA3 had
      antimicrobial activities against pathogenic microorganisms and proapoptotic
      effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide
      D-CopA3 had antimicrobial activities against various pathogenic bacteria and
      yeast fungus with MIC values in the 4~64 microM range. Moreover, D-CopA3 caused
      cell growth inhibition, and increased the chromosomal DNA fragmentation and the
      expression of inflammatory cytokines, TNF-alpha and IL1-beta, transcripts in
      human leukemia cells. The all-D amino acid peptide D-CopA3 proved as effective as
      the L-CopA3 reported previously. These results provide the basis for developing D
      CopA3 as a new antibiotic peptide.

PMID- 22370361
TI  - Effect of ammonium and nitrate on current generation using dual-cathode microbial
      fuel cells.
AB  - These studies were conducted to determine the effects of various concentrations
      of ammonium and nitrate on current generation using dual-cathode microbial fuel
      cells (MFCs). Current generation was not affected by ammonium up to 51.8+/-0.0
      mg/l, whereas 103.5+/-0.0 mg/l ammonium chloride reduced the current slightly. On
      the other hand, when 60.0+/-0.0 and 123.3+/-0.1 mg/l nitrate were supplied, the
      current was decreased from 10.23+/-0.07 mA to 3.20+/-0.24 and 0.20+/-0.01 mA,
      respectively. Nitrate did not seem to serve as a fuel for current generation in
      these studies. At this time, COD and nitrate removal were increased except at
      123+/-0.1 mg NO(3)(-)/l. These results show that proper management of ammonium
      and nitrate is very important for increasing the current in a microbial fuel
      cell.

PMID- 22370362
TI  - Efficacy test of Polycan, a beta-glucan originated from Aureobasidium pullulans
      SM-2001, on anterior cruciate ligament transection and partial medial
      meniscectomy-induced-osteoarthritis rats.
AB  - The object of this study was to assess the efficacy of Polycan from Aureobasidium
      pullulans SM-2001, which is composed mostly of beta-1,3-1,6-glucan, on
      osteoarthritis (OA)-induced by anterior cruciate ligament transection and partial
      medial meniscectomy (ACLT&PMM). Three different dosages of Polycan (85, 42.5, and
      21.25 mg/kg) were orally administered once a day for 84 days to male rats a week
      after ACLT&PMM surgery. Changes in the circumference and maximum extension angle
      of each knee, and in cartilage histopathology were assessed using Mankin scores
      12 weeks after Polycan administration. In addition, cartilage proliferation was
      evaluated using bromodeoxyuridine (BrdU). As the result of ACLT&PMM, classic OA
      was induced with increases in maximum extension angles, edematous knees changes,
      and capsule thickness, as well as decreases in chondrocyte proliferation,
      cartilages degenerative changes, and loss of articular cartilage. However, these
      changes (except for capsule thickness) were markedly inhibited in all Polycan-
      and diclofenac sodium-treated groups compared with OA control. Although
      diclofenac sodium did not influence BrdU uptake, BrdU-immunoreactive cells were
      increased with all dosages of Polycan, which means that Polycan treatment induced
      proliferation of chondrocytes in the surface articular cartilage of the tibia and
      femur. The results obtained in this study suggest that 84 days of continuous oral
      treatment of three different dosages of Polycan led to lesser degrees of
      articular stiffness and histological cartilage damage compared with OA controls
      91 days after OA inducement, suggesting that the optimal Polycan dosage to treat
      OA is 42.5 mg/kg based on the present study.

PMID- 22370363
TI  - Complex fragmentation of the articular surface of the distal radius:  management
      with small Kirschner wires and bone graft.
AB  - Severe intra-articular fractures of the distal radius with comminuted, displaced,
      and malrotated fragments are the most challenging fracture patterns.
      Reconstruction faces 3 major problems: fixation of fragments that are too small
      for stabilization by standard plates or screws, restoration of substantial
      cartilage loss in the articular surfaces, and extended metaphyseal/subchondral
      bony defects. For addressing these problems, a strategy is reported, by applying
      small, subchondrally placed Kirschner wires for the realignment of the articular
      surfaces, temporary inlay of a silicone foil in case of lost articular cartilage,
      and iliac crest bone grafting for bony defects. Stability is further augmented by
      buttress plates. This study reviews the historical perspective, indications,
      technique, complications, and rehabilitation of this strategy.

PMID- 22370364
TI  - Intramedullary fibular and impaction allografting in revision total elbow
      arthroplasty with endosteal deficiency.
AB  - One of the many reasons for failed revision elbow replacement is loss of the
      normally irregular shape of the endosteal surface leading to reduced ability to
      provide rotational control of the humeral or ulnar component within the
      intramedullary canal. The endosteal bone loss of the distal humerus or proximal
      ulna compromises the rotational stability of the stem in the intramedullary
      canal. In these cases, impaction cancellous allografting techniques, similar to
      the ones used in revision total hip arthroplasties, are commonly used to address
      the osseous deficiency, but these methods are not optimal for providing
      rotational control of the prosthetic stem. We describe a technique of restoring
      the irregular shape of the endosteal bone using intramedullary fibular
      allografting to enhance the rotational control of the prosthetic stem within the
      intramedullary bone canal.

PMID- 22370365
TI  - Use of aspiration thrombectomy in a 102-year-old patient with acute inferior ST
      segment elevation myocardial infarction.

PMID- 22370366
TI  - Late perforation of the ventricular ICD lead causes a pericarditis like ECG in a
      patient with Brugada syndrome.

PMID- 22370367
TI  - Positive remodeling is associated with vulnerable coronary plaque components
      regardless of clinical presentation: virtual histology-intravascular ultrasound
      analysis.
AB  - OBJECTIVE: We used virtual histology-intravascular ultrasound (VH-IVUS) to
      evaluate the relation between coronary artery remodeling pattern and plaque
      components in 1133 patients. METHODS: We divided the patients into two groups
      according to the remodeling pattern as positive remodeling (PR, remodeling
      index>1.05) (n=192) and intermediate remodeling (IR, remodeling index <= 1.05 and
      >= 0.95)/negative remodeling (NR, remodeling index<0.95) (n=941). VH-IVUS
      analysis classified the color-coded tissue into four major components: green
      (fibrotic, FT); yellow-green (fibro-fatty); white (dense calcium); and red
      (necrotic core, NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich
      (>= 10% of the cross-sectional area) plaques being in contact with the lumen in a
      plaque burden >= 40%. RESULTS: At the minimum lumen site, PR group had greater
      plaque plus media area (12.8 +/- 4.9 vs. 9.9 +/- 3.8mm(2), p<0.001) and greater
      %NC area (21.7 +/- 12.3 vs. 18.2 +/- 11.6%, p<0.001) and smaller %FT area (57.0
      +/- 14.5 vs. 59.4 +/- 14.6%, p=0.037) compared with IR/NR group. PR group had
      greater plaque volume (188 +/- 150 vs. 135 +/- 130 mm(3), p<0.001) and greater
      %NC volume (19.1 +/- 9.6 vs. 16.6 +/- 9.2%, p=0.001) and smaller %FT volume (58.3
      +/- 11.7 vs. 60.6 +/- 11.0%, p=0.009) compared with IR/NR group. PR group had
      more TCFA compared with IR/NR group (21% vs. 13%, p=0.006). Similar findings
      about plaque components were observed in terms of greater %NC volume and smaller
      %FT volume in PR group compared with IR/NR group in patients with both acute
      coronary syndrome and stable angina. CONCLUSIONS: VH-IVUS analysis demonstrates
      that PR was associated with more vulnerable plaque components compared with IR/NR
      regardless of their clinical presentation.

PMID- 22370368
TI  - Mirror image atrial dilatation in adult patients with atrial fibrillation and
      congenital heart disease.
AB  - BACKGROUND: Atrial fibrillation (AF) is largely regarded to be initiated from
      left atrial (LA) dilatation, with subsequent dilatation of the right atrium (RA)
      in those who progress to chronic AF. We hypothesized that in adult patients with
      right-sided congenital heart disease (CHD) and AF, RA dilatation will predominate
      with subsequent dilatation of the left atrium, as a mirror image. METHODS: Adult
      patients with diagnosis of right-sided, ASD or left-sided CHD who had undergone
      an echocardiographic study and electrocardiographic recording in 2007 were
      included. RA and LA area were measured from the apical view. AF was diagnosed
      from a 12-lead electrocardiogram or Holter recording. A multivariate logistic
      regression model was used to identify predictors of AF and linear regression
      models were performed to measure relationship between RA and LA area and AF.
      RESULTS: A total of 291 patients were included in the study. Multivariate
      analysis showed that age (p=0.0001), RA (p=0.025) and LA area (p=0.0016) were
      significantly related to AF. In patients with pure left-sided pathologies, there
      was progressive and predominant LA dilatation that paralleled the development of
      AF from none to paroxysmal to chronic AF. In patients with pure right-sided
      pathologies, there was a mirror image of progressive and predominant RA
      dilatation with the development of AF. CONCLUSION: We observed a mirror image
      atrial dilatation in patients with right sided disease and AF. This may provide
      novel mechanistic insight as to the origin of AF in these patients and deserves
      further studying in the form of targeted electrophysiological studies.

PMID- 22370369
TI  - Heart rate stability and decreased parasympathetic heart rate variability in
      healthy young adults during perceived stress.

PMID- 22370370
TI  - Increased risk for ascending aortic dilatation in patients with complex compared
      to simple aortic coarctation.
AB  - AIMS: Aortic coarctation (CoA) occurs as a "simple" isolated disorder, and in a
      more "complex" form, combined with associated congenital cardiac abnormalities.
      Long term outcome of all CoA patients may be complicated by dilatation of the
      thoracic aorta. The aim of this study was to quantify progressive aortic
      dilatation, and identify determinants for progressive aortic dilatation. METHODS
      AND RESULTS: Cardiovascular Magnetic Resonance Imaging (CMR) and
      echocardiographic data of 93 CoA patients were analyzed retrospectively on the
      progression, and determinants, of progressive thoracic aortic dilatation. Outcome
      of simple- versus complex CoA patients were compared. 93 CoA patients (mean age
      39 +/- 12 years, male 59%) were followed with CMR (follow-up 5.3 +/- 1.8 years).
      Twenty-eight patients were classified as simple- and 68 as complex CoA. The mean
      progression rate of thoracic aortic dilatation was highest in the ascending aorta
      with 2.2 +/- 2.0mm/5 years (range 0-7.2mm/5 years). History of VSD (beta=1.77,
      P=0.004) and an increased left ventricular mass index (beta=0.02, P=0.04) were
      associated with progressive ascending aortic dilatation. Complex CoA patients
      show an increased progression rate compared to simple CoA patients with 2.4mm/5
      years versus 1.5mm/5 years respectively. (P=0.03). CONCLUSION: Adult post
      coarctectomy patients show an increased mean progression rate of ascending aortic
      dilatation with 2.2mm/5 years. The progression rate of ascending aortic
      dilatation is increased in complex CoA patients, as compared to simple CoA
      patients. These findings point towards a more comprehensive genetic subset of
      patients with an increased risk for progressive ascending aortic dilatation.

PMID- 22370371
TI  - Comparison of two-dimensional longitudinal strain with rest single photon
      emission tomography perfusion imaging for transmural scar identification in
      patients with ischemic left ventricular systolic dysfunction.

PMID- 22370372
TI  - The efficacy and safety of drug-eluting stents in patients with acute myocardial
      infarction: results from Korea Acute Myocardial Infarction (KAMIR).
AB  - There are controversies about the use of drug-eluting stent (DES) in patients
      with acute myocardial infarction (AMI). Recent trials of DES in patients with AMI
      have shown the relative safety of DES. However, some physicians hesitate to use
      DES in AMI patients because of increased risk of stent thrombosis and death. We
      summarized in this article about the efficacy and safety of DES in AMI patients
      who were enrolled in Korea Acute Myocardial Infarction Registry (KAMIR).

PMID- 22370373
TI  - Accuracy and pharmacist perceptions of community-based automated blood pressure
      machines: response to Wiggers-Porta et al.

PMID- 22370376
TI  - Opportunities multiply as they are seized.

PMID- 22370377
TI  - Current trends in outpatient pharmacy services and billing.
AB  - OBJECTIVES: To provide a summary of community and ambulatory pharmacy practices
      and billing patterns for medication therapy management (MTM) services and to
      identify reasons pharmacists report not billing for direct patient care services.
      DESIGN: Cross-sectional study. SETTING: United States, February 2011.
      PARTICIPANTS: Members of the American College of Clinical Pharmacy Ambulatory
      Care Practice and Research Network, American Society of Health-System Pharmacists
      Ambulatory and Chronic Care Practitioners, and American Pharmacists Association
      MTM e-community. INTERVENTION: Online survey. MAIN OUTCOME MEASURES: Practice
      setting, pharmacy services performed, billing technique, and payer, as well as
      reasons for not billing. RESULTS: MTM services were provided by 287 pharmacists.
      The most common practice settings included physician office (23.6%), health
      system outpatient facility (21.7%), and community pharmacy (20.2%). A total of
      149 of 276 pharmacists (54.0%) reported billing for MTM services; 16 of 276
      (5.8%) did not know if they were currently billing. Community pharmacists were
      more likely to bill than all other sites combined (80.5% vs. 53.1%, P < 0.001),
      and pharmacists with >75% of visits face-to-face were more likely to bill (66.2%
      vs. 46.6%, P < 0.002). CONCLUSION: A variety of MTM services are provided in
      outpatient settings with inconsistent billing techniques and reimbursement.
      Pharmacists should continue to work toward consistent, sustainable reimbursement
      to expand MTM services.

PMID- 22370378
TI  - Reimbursement model for pharmacist-directed medication therapy management.
AB  - OBJECTIVE: To describe the development of a practice model with sustainable
      reimbursement for medication therapy management (MTM) services provided by
      pharmacists for beneficiaries of self-insured health care plans. PRACTICE
      DESCRIPTION: The Auburn University Pharmaceutical Care Center (AUPCC) is a free
      standing clinic located within the school of pharmacy that provides preventive
      care and MTM services for a population of 11,600 employees and dependents that
      subscribe to the university's self-insured health plan. The goal of patient care
      is to increase use of cost-effective pharmacotherapy and improve the outcomes of
      medication use among the population. MAIN OUTCOME MEASURES: Development and
      implementation of a practice model and reimbursement method that can be
      implemented in the employer setting for large self-insured employers and the
      community pharmacy practice setting. RESULTS: Since opening, AUPCC has developed
      into a model pharmaceutical care service that can be implemented in the workplace
      for other self-insured employers. AUPCC is also a model that can easily translate
      to the community pharmacy setting. In 2010, the model was adapted by Alabama for
      state employees. CONCLUSION: Pharmacists can negotiate directly with decision
      makers within large companies that are self-insured to provide MTM services for
      the employee population. This is an area of sustainable growth within our
      profession.

PMID- 22370379
TI  - Evaluation of pharmacist-provided medication therapy management services in an
      oncology ambulatory setting.
AB  - OBJECTIVES: To determine the effect of formal medication therapy management (MTM)
      services on pharmacist workload, as well as to describe the population receiving
      MTM, describe the services provided, and determine the reimbursement rate for
      billed MTM services. DATA SOURCES: MTM Current Procedural Terminology (CPT) code
      claims, electronic medical records, and pharmacist MTM logs. DATA SYNTHESIS: A
      retrospective review of all MTM charges from January 1, 2010, to March 31, 2010,
      was performed. Data collected included location of the MTM visit, age, gender,
      insurance, primary malignancy, comorbidities, home medications, time to complete
      and document the MTM visit, and rate of reimbursement. RESULTS: In the 3-month
      period, 239 MTM visits were completed. It took pharmacists a median of 20 minutes
      (range 15-127) of face-to-face time and 18 minutes (5-90) for documentation per
      visit. To date, no claims for MTM have been rejected, and reimbursement rates
      range from 47% to 79% depending on the insurance provider. CONCLUSIONS: MTM in
      the ambulatory clinic is feasible despite the increase in pharmacist workload
      from documenting and billing. The increased visibility of clinical pharmacy
      services justifies the extra time required for formal MTM.

PMID- 22370380
TI  - Billing for pharmacists' cognitive services in physicians' offices: multiple
      methods of reimbursement.
AB  - OBJECTIVES: To evaluate the charges and reimbursement for pharmacist services
      using multiple methods of billing and determine the number of patients that must
      be managed by a pharmacist to cover the cost of salary and fringe benefits.
      SETTING: Large teaching ambulatory clinic in North Carolina. MAIN OUTCOME
      MEASURES: Annual charges and reimbursement, patient no-show rate, clinic
      capacity, number of patients seen monthly and annually, and number of patients
      that must be seen to pay for a pharmacist's salary and benefits. RESULTS: A total
      of 6,930 patient encounters were documented during the study period. Four
      different clinics were managed by the pharmacists, including anticoagulation,
      pharmacotherapy, osteoporosis, and wellness clinics. "Incident to" level 1
      billing was used for the anticoagulation and pharmacotherapy clinics, whereas
      level 4 codes were used for the osteoporosis clinic. The wellness clinic utilized
      a negotiated fee-for-service model. Mean annual charges were $65,022, and the
      mean reimbursement rate was 47%. The mean charge and collection per encounter
      were $41 and $19, respectively. Eleven encounters per day were necessary to
      generate enough charges to pay for the cost of the pharmacist. Considering actual
      reimbursement rates, the number of patient encounters necessary increased to 24
      per day. "What if" sensitivity analysis indicated that billing at the level of
      service provided instead of level 1 decreased the number of patients needed to be
      seen daily. Billing a level 4 visit necessitated that five patients would need to
      be seen daily to generate adequate charges. Taking into account the 47%
      reimbursement rate, 10 level 4 encounters per day were necessary to generate
      appropriate reimbursement to pay for the pharmacist. CONCLUSION: Unique
      opportunities for pharmacists to provide direct patient care in the ambulatory
      setting continue to develop. Use of a combination of billing methods resulted in
      sustainable reimbursement. The ability to bill at the level of service provided
      instead of a level 1 visit would decrease the number of patients needed to pay
      for a pharmacist.

PMID- 22370381
TI  - Three-year financial analysis of pharmacy services at an independent community
      pharmacy.
AB  - OBJECTIVE: To assess the financial performance of pharmacy services including
      vaccinations, cholesterol screenings, medication therapy management (MTM),
      adherence management services, employee health fairs, and compounding services
      provided by an independent community pharmacy. METHODS: Three years (2008-10) of
      pharmacy records were examined to determine the total revenue and costs of each
      service. Costs included products, materials, labor, marketing, overhead,
      equipment, reference materials, and fax/phone usage. Costs were allocated to each
      service using accepted principles (e.g., time for labor). Depending on the
      service, the total revenue was calculated by multiplying the frequency of the
      service by the revenue per patient or by adding the total revenue received. A
      sensitivity analysis was conducted for the adherence management services to
      account for average dispensing net profit. RESULTS: 7 of 11 pharmacy services
      showed a net profit each year. Those services include influenza and herpes zoster
      immunization services, MTM, two adherence management services, employee health
      fairs, and prescription compounding services. The services that realized a net
      loss included the pneumococcal immunization service, cholesterol screenings, and
      two adherence management services. The sensitivity analysis showed that all
      adherence services had a net gain when average dispensing net profit was
      included. CONCLUSION: Most of the pharmacist services had an annual positive net
      gain. It seems likely that these services can be sustained. Further cost
      management, such as reducing labor costs, could improve the viability of services
      with net losses. However, even with greater efficiency, external factors such as
      competition and reimbursement challenge the sustainability of these services.

PMID- 22370382
TI  - Blood pressure kiosks for medication therapy management programs: business
      opportunity for pharmacists.
AB  - OBJECTIVE: To develop an economic model based on the use of pharmacy-based blood
      pressure kiosks for case finding of remunerable medication therapy management
      (MTM) opportunities. DESIGN: Descriptive, exploratory, nonexperimental study.
      SETTING: Ontario, Canada, between January 2010 and September 2011. PATIENTS: More
      than 7.5 million blood pressure kiosk readings were taken from 341 pharmacies.
      INTERVENTION: A model was developed to estimate revenues achievable by using
      blood pressure kiosks for 1 month to identify a cohort of patients with blood
      pressure of 130/80 mm Hg or more and caring for those patients during 1 year.
      MAIN OUTCOME MEASURE: Revenue generated from MTM programs. RESULTS: Pharmacies
      could generate an average of $12,270 (range $4,523-24,420) annually in revenue
      from billing for MTM services. CONCLUSION: Blood pressure kiosks can be used to
      identify patients with elevated blood pressure who may benefit from reimbursable
      pharmacist cognitive services. Revenue can be reinvested to purchase automated
      dispensing technology or offset pharmacy technician costs to free pharmacists to
      provide pharmaceutical care. Improved patient outcomes, increased patient
      loyalty, and improved adherence are additional potential benefits.

PMID- 22370383
TI  - Role of the pharmacist in preventing distribution of counterfeit medications.
AB  - OBJECTIVE: To provide an overview of the counterfeit medication problem and
      recommendations of a joint American Pharmacists Association (APhA) Academy of
      Pharmaceutical Research and Science and APhA Academy of Pharmacy Practice and
      Management taskforce. DATE SOURCES: SciFinder and PubMed were searched from 1980
      to March 2011 using the following keywords: counterfeit drug product, counterfeit
      medications, drug product authentication, drug product verification, and track
      and-trace. Publications, presentations, and websites of organizations that
      research the counterfeit medication problem in the United States and other
      countries were reviewed. A representative from the security division of a
      pharmaceutical manufacturer and a representative from a supplier of
      anticounterfeiting technologies gave presentations to the taskforce. SUMMARY: The
      taskforce recommends that pharmacists (1) purchase medications from known,
      reliable sources; (2) warn patients of the dangers of purchasing medications over
      the Internet; (3) confirm with distributors that products were purchased from
      manufacturers or other reliable sources; (4) monitor counterfeit product alerts;
      (5) examine products for suspicious appearance; (6) work with the pharmaceutical
      industry, distributors, and the Food and Drug Administration (FDA) to close gaps
      in the supply chain, especially for drugs in short supply; (7) use scanning
      technology in the pharmacy as part of a prescription verification process; (8)
      educate themselves, coworkers, and patients about the risks of counterfeit
      medications; and (9) report suspicious medications to FDA, the distributor, and
      the manufacturer. CONCLUSION: The consequence of a patient receiving a
      counterfeit medication in the United States could be catastrophic, and
      pharmacists must play an active role in preventing such an event from occurring.

PMID- 22370386
TI  - Quadrivalent human papillomavirus vaccine: updated recommendations for males.

PMID- 22370387
TI  - Aflibercept, ipilimumab, and vemurafenib.

PMID- 22370388
TI  - Science snippets. Reducing Medicare Part D cost to patient, drug-induced QT
      interval lengthening, and suicide and leukotriene-modifying agents.

PMID- 22370390
TI  - Transport routes of metalloids into and out of the cell: a review of the current
      knowledge.
AB  - Except for their extra- and intra-cellular interfaces, cell membranes are
      hydrophobic and inhibit the transport of hydrophilic molecules. Metalloids in
      aqueous solutions form chemical species with oxygen and hydroxyl groups and,
      therefore, exist as hydrophilic neutral polar solutes or as hydrophilic anions.
      This characteristic of metalloids introduces a large barrier for their passage
      through the cell membrane via unaided diffusion. The necessity for an uptake
      mechanism for metalloids arises from the requirement of these species for the
      maintenance of life, such as the need of boron for plant cells. Conversely, the
      transport of these species out of the cell is necessary because some metalloids
      are toxic, such as arsenic and antimony, and their entrance into the cell is
      undesirable. The undesired uptake of these toxic species is possible via pathways
      designed for the uptake of other structurally and chemically similar essential
      compounds. Therefore, the extrusion of arsenic and antimony out of the cell is an
      example of a detoxification mechanism. As a consequence of the hydrophobic
      character of the cell membrane in all living systems, the main route for the
      uptake and efflux of metalloids is facilitated by transmembrane proteins, driven
      either by concentration gradients or by energy-fueled pumps. However, metalloids
      forming or embedded in nano-sized particles escape the need to cross the cell
      membrane because these particles can be taken into the cell by endocytosis. Here,
      we review the uptake and efflux pathways of boron, silicon, arsenic, and antimony
      through the cell membranes of different organisms and the protein channels
      involved in these processes. In particular, passive diffusion via
      aquaglyceroporins, active transport via primary and secondary ion pumps,
      extrusion into vacuoles of metalloid-thiol conjugates via ATP-binding cassette,
      the efflux of methylated metalloids, and endocytosis are summarized.

PMID- 22370391
TI  - Riparian buffer strips as a multifunctional management tool in agricultural
      landscapes: introduction.
AB  - Catchment riparian areas are considered key zones to target mitigation measures
      aimed at interrupting the movement of diffuse substances from agricultural land
      to surface waters. Hence, unfertilized buffer strips have become a widely studied
      and implemented "edge of field" mitigation measure assumed to provide an
      effective physical barrier against nitrogen (N), phosphorus (P), and sediment
      transfer. To ease the legislative process, these buffers are often narrow
      mandatory strips along streams and rivers, across different riparian soil water
      conditions, between bordering land uses of differing pollution burdens, and
      without prescribed buffer management. It would be easy to criticize such
      regulation for not providing the opportunity for riparian ecosystems to maximize
      their provision for a wider range of ecosystem goods and services. The scientific
      basis for judging the best course of action in designing and placing buffers to
      enhance their multifunctionality has slowly increased over the last five years.
      This collection of papers aims to add to this body of knowledge by giving
      examples of studies related to riparian buffer management and assessment
      throughout Europe. This introductory paper summarizes discussion sessions and 13
      selected papers from a workshop held in Ballater, UK, highlighting research on
      riparian buffers brought together under the EU COST Action 869 knowledge exchange
      program. The themes addressed are (i) evidence of catchment- to national-scale
      effectiveness, (ii) ecological functioning linking terrestrial and aquatic
      habitats, (iii) modeling tools for assessment of effectiveness and costs, and
      (iv) process understanding enabling management and manipulation to enhance
      pollutant retention in buffers. The combined understanding led us to consider
      four principle key questions to challenge buffer strip research and policy.

PMID- 22370392
TI  - Phosphorus load to surface water from bank erosion in a Danish lowland river
      basin.
AB  - Phosphorus loss from bank erosion was studied in the catchment of River Odense, a
      lowland Danish river basin, with the aim of testing the hypothesis of whether
      stream banks act as major diffuse phosphorus (P) sources at catchment scale.
      Furthermore, the study aimed at analyzing the impact of different factors
      influencing bank erosion and P loss such as stream order, anthropogenic
      disturbances, width of uncultivated buffer strips, and the vegetation of buffer
      strips. A random stratified procedure in geographical information system (GIS)
      was used to select two replicate stream reaches covering different stream orders,
      channelized vs. naturally meandering channels, width of uncultivated buffer
      strips (<= 2 m and >= 10 m), and buffer strips with different vegetation types.
      Thirty-six 100-m stream reaches with 180 bank plots and a total of 3000 erosion
      pins were established in autumn 2006, and readings were conducted during a 3-yr
      period (2006-2009). The results show that neither stream size nor stream
      disturbance measured as channelization of channel or the width of uncultivated
      buffer strip had any significant ( < 0.05) influence on bank erosion and P losses
      during each of the 3 yr studied. In buffer strips with natural trees bank erosion
      was significantly ( < 0.05) lower than in buffer strips dominated by grass and
      herbs. Gross and net P input from bank erosion amounted to 13.8 to 16.5 and 2.4
      to 6.3 t P, respectively, in the River Odense catchment during the three study
      years. The net P input from bank erosion equaled 17 to 29% of the annual total P
      export and 21 to 62% of the annual export of P from diffuse sources from the
      River Odense catchment. Most of the exported total P was found to be bioavailable
      (71.7%) based on a P speciation of monthly suspended sediment samples collected
      at the outlet of the river basin. The results found in this study have a great
      importance for managers working with P mitigation and modeling at catchment
      scale.

PMID- 22370393
TI  - The Tarland Catchment Initiative and its effect on stream water quality and
      macroinvertebrate indices.
AB  - The Tarland Catchment Initiative is a partnership venture between researchers,
      land managers, regulators, and the local community. Its aims are to improve water
      quality, promote biodiversity, and increase awareness of catchment management. In
      this study, the effects of buffer strip installations and remediation of a large
      septic tank effluent were appraised by water physico-chemistry (suspended solids,
      NO, NH, soluble reactive P) and stream macroinvertebrate indices used by the
      Scottish Environmental Protection Agency. It was done during before and after
      interventions over an 8-yr period using a paired catchment approach. Because
      macroinvertebrate indices were previously shown to respond negatively to
      suspended solid concentrations in the study area, the installation of buffer
      strips along the headwaters was expected to improve macroinvertebrate scores.
      Although water quality (soluble reactive P, NH) improved downstream of the septic
      tank effluent after remediation, there was no detectable change in
      macroinvertebrate scores. Buffer strip installations in the headwaters had no
      measurable effects (beyond possible weak trends) on water quality or
      macroinvertebrate scores. Either the buffer strips have so far been ineffective
      or ineffectiveness of assessment methods and sampling frequency and time lags in
      recovery prevent us detecting reliable effects. To explain and appreciate these
      constraints on measuring stream recovery, continuous capacity building with land
      managers and other stakeholders is essential; otherwise, the feasibility of
      undertaking sufficient management interventions is likely to be compromised and
      projects deemed unsuccessful.

PMID- 22370394
TI  - Effectiveness of unfertilized buffer strips for reducing nitrogen loads from
      agricultural lowland to surface waters.
AB  - Unfertilized buffer strips (BS) are widely accepted to reduce nitrogen (N) loads
      from agricultural land to surface water. However, the relative reduction of N
      load or concentration (BS effectiveness, BSE), varies with management and local
      conditions, especially hydrogeology. We present novel experimental evidence on
      BSE for 5-m-wide grass BS on intensively drained and managed plain agricultural
      lowland with varying hydrogeology. We selected characteristic sites for five
      major hydrogeological classes of the Netherlands and installed paired 5-m-wide
      unfertilized grass (BS) and reference (REF) treatments along the ditch. The REF
      was managed like the adjacent field, and BS was only harvested. Treatments were
      equipped with reservoirs in the ditch to collect and measure discharge and flow
      proportional N concentration for 3 or 4 yr. In addition, N concentration in upper
      groundwater was measured. We found a statistically significant BSE of 10% on the
      peat site. At the other sites, BSE for N was low and statistically insignificant.
      Low BSE was explained by denitrification between adjacent field and ditch, as
      well as by the site-specific hydrologic factors including low proportion of
      shallow groundwater flow, downward seepage, low residence time in the BS, and
      surface runoff away from the ditch. We emphasize that a REF treatment is needed
      to evaluate BSE in agriculture and recommend reservoirs if drainage patterns are
      unknown. Introduction of a 5-m-wide BS is ineffective for mitigating N loads from
      lowland agriculture to surface waters. We expect more from BS specifically
      designed to abate surface runoff.

PMID- 22370395
TI  - A novel method to determine buffer strip effectiveness on deep soils.
AB  - Unfertilized buffer strips (BS) generally improve surface water quality. High
      buffer strip effectiveness (BSE) has been reported for sloping shallow aquifers,
      but experimental data for plain landscapes with deeply permeable soils is
      lacking. We tested a novel method to determine BSE on a 20-m-deep, permeable
      sandy soil. Discharge from soil to ditch was temporarily collected in an in
      stream reservoir to measure its quantity and quality, both for a BS and a
      reference (REF) treatment. Treatments were replicated once for the first, and
      three times for the next three leaching seasons. No significant BSE was obtained
      for nitrogen and phosphorus species in the reservoirs. Additionally, water
      samples were taken from the upper groundwater below the treatments. The effect of
      BS for nitrate was much bigger in upper groundwater than in the reservoirs that
      also collected groundwater from greater depths that were not influenced by the
      treatments. We conclude that measuring changes in upper groundwater to assess BSE
      is only valid under specific hydrogeological conditions. We propose an
      alternative experimental set-up for future research, including extra measurements
      before installing the BS and REF treatments to deal with spatial and temporal
      variability. The use of such data as covariates will increase the power of
      statistical tests by decreasing between-reservoir variability.

PMID- 22370396
TI  - Diversity and distribution of riparian plant communities in relation to stream
      size and eutrophication.
AB  - The present study was conducted in 47 different riparian areas distributed
      throughout Denmark to investigate diversity and distributional patterns of plant
      communities along a lowland stream size gradient (first to fifth order). The
      investigated areas were representative for Danish riparian areas not in use for
      agricultural production. We investigated plant community richness along a stream
      size gradient and the influence of eutrophication on the abundance of different
      plant communities. Vegetation analyses were performed in transects placed
      perpendicular to the stream channel, with a total of 1798 plots analyzed.
      Overall, we found a positive relationship between stream mean depth as a measure
      of stream size and the number of plant community types identified in the riparian
      areas. We also found that the abundance of the identified communities was
      positively correlated with their nutrient preference and negatively correlated
      with their moisture preference. The abundance of alkaline fens and Molinia
      meadows (protected community types) in riparian areas decreased with increasing
      size of the stream, whereas the abundance of humid meadows and wet herb fringes
      increased with increasing size of the stream. Based on our findings, we recommend
      that wide buffer zones be established along streams with protected habitat types
      in the associated riparian areas to reduce the direct impact from agriculture.
      Furthermore, we recommend that wide buffer zones be established along middle
      sized and large streams because several community types may develop.

PMID- 22370397
TI  - Improving the farmland biodiversity value of riparian buffer strips: conflicts
      and compromises.
AB  - The intensity of management of lowland grassland fields in the United Kingdom,
      coupled with the fact that such grasslands dominate much of the lowland
      landscape, means that there are now few opportunities for many plants,
      invertebrates, birds, or mammals to survive. The Scottish Agricultural College
      (SAC) has investigated whether fencing off the margins of such fields next to
      watercourses to control diffuse pollution has any positive impacts on
      biodiversity, based on assessments of vegetation composition and condition and
      structure of assemblages of invertebrates of importance as foodstuffs to farmland
      birds. Fencing watercourses increased the abundance of key groups of
      invertebrates. However, the invertebrate species diversity was not increased
      unless the margins were >= 5.4 m in width. Margins established in the study area
      to prevent access by livestock to watercourses or to enhance biodiversity are
      generally <= 2.6 m wide and are therefore unlikely to provide conditions for
      additional invertebrate species to use. The dense, tall swards within such
      margins are also unlikely to provide foraging opportunities for farmland birds.
      Management (such as low-intensity grazing by livestock in the margins) is
      essential to provide the conditions required for these groups, but this could
      conflict with the diffuse pollution mitigation aims. A compromise is proposed
      whereby limited autumn/winter grazing by livestock could be used to open the
      vegetation structure in the margins. Grazing by livestock at that time may be
      acceptable since it is not occurring in the period of main diffuse pollution
      concern (i.e., the fecal contamination of watercourses and bathing waters in the
      spring and summer). It is also essential that a landscape-scale approach is
      taken, driven by knowledge of the full needs of the species concerned, when
      deciding where best to target agri-environmental actions aimed at farmland bird
      conservation.

PMID- 22370398
TI  - Investigating riparian margins for vegetation patterns and plant-environment
      relationships in northeast Scotland.
AB  - Buffer strips alongside watercourses are a widely accepted method of reducing
      nutrient and sediment run-off from agricultural land thereby improving water
      quality. Little attention, however, has been paid to the ecological status of
      these areas despite the fact that riparian habitats in good condition can provide
      multiple benefits. We investigated vegetation patterns and plant-environment
      relationships within three categories of riparian margins in northeast Scotland.
      The margins were categorized as unbuffered, buffered, or reference (target), the
      latter representing the best sites available within the catchments. Vascular
      plant and soil data were collected from 41 sites along the tributaries of two
      rivers during 2008 and 2009. Ellenberg indicator values revealed trends of
      decreasing light availability ( < 0.05) and decreasing pH ( < 0.01) from
      unbuffered sites to buffered sites to reference sites. Multivariate analysis
      showed that soil parameters and channel morphology, together with canopy cover
      and bryophyte abundance, were discriminatory in separating species assemblages.
      The presence of a tree canopy layer appears to be the key instigator of change in
      soil conditions and corresponding plant species assemblages. An understanding of
      the underlying processes is important if vegetation characteristics are to be
      used effectively as indicators of riparian and water quality and to aid the
      restoration of riparian habitats.

PMID- 22370399
TI  - Effects of riparian forest buffers on in-stream nutrient retention in
      agricultural catchments.
AB  - In northeastern Austria, marshlands have been turned into the most productive
      arable land of the country. As a result, most headwater streams show structurally
      degraded channels, lacking riparian buffer zones, which are heavily loaded with
      nutrients from the surrounding crop fields. The present study examines whether
      longitudinally restricted riparian forest buffers can enhance the in-stream
      nutrient retention in nutrient-enriched headwater streams. We estimated nutrient
      uptake from pairwise, short-term addition experiments with NH, NH, PO, and NaCl
      within reaches with riparian forest buffers (RFB) and degraded reaches (DEG) of
      the same streams. Riparian forest buffers originated from the conservation of the
      pristine vegetation or from restoration measures. Hydrologic retention was
      calculated with the model OTIS-P on the basis of conductivity break-through
      curves from the salt injections. A significant increase in surface transient
      storage was revealed in pristine and restored RFB reaches compared with DEG
      reaches due to the longitudinal step-pool pattern and the frequent occurrence of
      woody debris on the channel bed. Ammonium uptake lengths were significantly
      shorter in RFB reaches than in DEG reaches, resulting from the higher hydrologic
      retention. Uptake velocities did not differ significantly between RFB and DEG
      reaches, indicating that riparian forest buffers did not affect the biochemical
      nutrient demand. Uptake of NH was mainly driven by autotrophs. Net PO uptake was
      not affected by riparian forest buffers. The study shows that the physical and
      biogeochemical effects of riparian forest buffers on the in-stream nutrient
      retention are limited in the case of highly eutrophic streams.

PMID- 22370400
TI  - Integrating economic and biophysical data in assessing cost-effectiveness of
      buffer strip placement.
AB  - The European Union Water Framework Directive (WFD) requires Member States to set
      water quality objectives and identify cost-effective mitigation measures to
      achieve "good status" in all waters. However, costs and effectiveness of measures
      vary both within and between catchments, depending on factors such as land use
      and topography. The aim of this study was to develop a cost-effectiveness
      analysis framework for integrating estimates of phosphorus (P) losses from land
      based sources, potential abatement using riparian buffers, and the economic
      implications of buffers. Estimates of field-by-field P exports and routing were
      based on crop risk and field slope classes. Buffer P trapping efficiencies were
      based on literature metadata analysis. Costs of placing buffers were based on
      foregone farm gross margins. An integrated optimization model of cost
      minimization was developed and solved for different P reduction targets to the
      Rescobie Loch catchment in eastern Scotland. A target mean annual P load
      reduction of 376 kg to the loch to achieve good status was identified. Assuming
      all the riparian fields initially have the 2-m buffer strip required by the
      General Binding Rules (part of the WFD in Scotland), the model gave good
      predictions of P loads (345-481 kg P). The modeling results show that riparian
      buffers alone cannot achieve the required P load reduction (up to 54% P can be
      removed). In the medium P input scenario, average costs vary from L38 to L176 kg
      P at 10% and 54% P reduction, respectively. The framework demonstrates a useful
      tool for exploring cost-effective targeting of environmental measures.

PMID- 22370401
TI  - Phosphorus retention and remobilization in vegetated buffer strips: a review.
AB  - Diffuse pollution remains a major threat to surface waters due to eutrophication
      caused by phosphorus (P) transfer from agricultural land. Vegetated buffer strips
      (VBSs) are increasingly used to mitigate diffuse P losses from agricultural land,
      having been shown to reduce particulate P transfer. However, retention of
      dissolved P (DP) has been lower, and in some cases VBSs have increased delivery
      to surface waters. The aims of this review were (i) to develop a conceptual model
      to enhance the understanding of VBS functioning in terms of DP, (ii) to identify
      key processes within the model that affect DP retention and delivery, and (iii)
      to explore evidence for the controls on these processes. A greater understanding
      in these areas will allow the development of management strategies that enhance
      DP retention. We found evidence of a surface layer in buffer strip soils that is
      enriched in soluble P compared with adjacent agricultural land and may be
      responsible for the reported increased DP delivery. Through increased biological
      activity in VBSs, plants and microorganisms may assimilate P from particulates
      retained in the VBSs or native soil P and remobilize this P in a more soluble
      form. These conclusions are based on a limited amount of research, and a better
      understanding of biogeochemical cycling of P in buffer strip soils is required.

PMID- 22370402
TI  - Relationships between soil physicochemical, microbiological properties, and
      nutrient release in buffer soils compared to field soils.
AB  - The retention of nutrients in narrow, vegetated riparian buffer strips (VBS) is
      uncertain and underlying processes are poorly understood. Evidence suggests that
      buffer soils are poor at retaining dissolved nutrients, especially phosphorus
      (P), necessitating management actions if P retention is not to be compromised. We
      sampled 19 buffer strips and adjacent arable field soils. Differences in nutrient
      retention between buffer and field soils were determined using a combined assay
      for release of dissolved P, N, and C forms and particulate P. We then explored
      these differences in relation to changes in soil bulk density (BD), moisture,
      organic matter by loss on ignition (OM), and altered microbial diversity using
      molecular fingerprinting (terminal restriction fragment length polymorphism
      [TRFLP]). Buffer soils had significantly greater soil OM (89% of sites), moisture
      content (95%), and water-soluble nutrient concentrations for dissolved organic C
      (80%), dissolved organic N (80%), dissolved organic P (55%), and soluble reactive
      P (70%). Buffer soils had consistently smaller bulk densities than field soils.
      Soil fine particle release was generally greater for field than buffer soils.
      Significantly smaller soil bulk density in buffer soils than in adjacent fields
      indicated increased porosity and infiltration in buffers. Bacterial, archaeal,
      and fungal communities showed altered diversity between the buffer and field
      soils, with significant relationships with soil BD, moisture, OM, and increased
      solubility of buffer nutrients. Current soil conditions in VBS appear to be
      leading to potentially enhanced nutrient leaching via increasing solubility of C,
      N, and P. Manipulating soil microbial conditions (by management of soil moisture,
      vegetation type, and cover) may provide options for increasing the buffer storage
      for key nutrients such as P without increasing leaching to adjacent streams.

PMID- 22370403
TI  - Long-term field-scale experiment on using lime filters in an agricultural
      catchment.
AB  - The River Ylaneenjoki catchment in southwest Finland is an area with a high
      agricultural nutrient load. We report here on the nutrient removal performance of
      three on-site lime-sand filters (F1, F2, and F3), established within or on the
      edge of the buffer zones. The filters contain burnt lime (CaO) or spent lime
      [CaO, Ca(OH), and CaCO]. Easily soluble lime results in a high pH level (>11) and
      leads to an efficient precipitation of soluble phosphorus (P) from the runoff.
      Water samples were taken from the inflow and outflow of each site in different
      hydrological situations. The length of the monitoring period was 4 yr for F1, 6
      yr for F2, and 1.5 yr for F3. F1 and F2 significantly reduced the suspended
      solids (SS), total P (PTOT), and dissolved reactive P (DRP) in the treated water.
      The proportional reduction (%) varied but was usually clearly positive. Filter F3
      was divided into two equal parts, one containing burnt lime and the other spent
      lime. Both filter parts removed PTOT and SS efficiently from the water; the burnt
      lime part also removed DRP. The mixed-lime part removed DRP for a year, but then
      the efficiency decreased. The effect of filters on nitrogen compounds varied. We
      conclude that sand filters incorporating lime can be used together with buffer
      zones to reduce both P and SS load to watercourses.

PMID- 22370404
TI  - Phosphorus mitigation during springtime runoff by amendments applied to grassed
      soil.
AB  - Permanent grass vegetation on sloping soils is an option to protect fields from
      erosion, but decaying grass may liberate considerable amounts of dissolved
      reactive P (DRP) in springtime runoff. We studied the effects of freezing and
      thawing of grassed soil on surface runoff P concentrations by indoor rainfall
      simulations and tested whether the peak P concentrations could be reduced by
      amending the soil with P-binding materials containing Ca or Fe. Forty grass
      vegetated soil blocks (surface area 0.045 m, depth 0.07 m) were retrieved from
      two permanent buffer zones on a clay and loam soil in southwest Finland. Four
      replicates were amended with either: (i) gypsum from phosphoric acid processing
      (CaSO * 2HO, 6 t ha), (ii) chalk powder (CaCO, 3.3 t ha), (iii) Fe-gypsum (6 t
      ha) from TiO processing, or (iv) granulated ferric sulfate (Fe[SO], 0.7 t ha),
      with four replicates serving as untreated controls. Rainfall (3.3 h * 5 mm h) was
      applied on presaturated samples set at a slope of 5% and the surface runoff was
      analyzed for DRP, total dissolved P (TDP), total P (TP), and suspended solids.
      Rainfall simulation was repeated twice after the samples were frozen. Freezing
      and thawing of the samples increased the surface runoff DRP concentration of the
      control treatment from 0.19 to 0.46 mg L, up to 2.6-3.7 mg L, with DRP being the
      main P form in surface runoff. Compared with the controls, surface runoff from
      soils amended with Fe compounds had 57 to 80% and 47 to 72% lower concentrations
      of DRP and TP, respectively, but the gypsum and chalk powder did not affect the P
      concentrations. Thus, amendments containing Fe might be an option to improve DRP
      retention in, e.g., buffer zones.

PMID- 22370405
TI  - Nitrous oxide emissions respond differently to mineral and organic nitrogen
      sources in contrasting soil types.
AB  - The use of various animal manures for nitrogen (N) fertilization is often viewed
      as a viable replacement for mineral N fertilizers. However, the impacts of
      amendment type on NO production may vary. In this study, NO emissions were
      measured for 2 yr on two soil types with contrasting texture and carbon (C)
      content under a cool, humid climate. Treatments consisted of a no-N control,
      calcium ammonium nitrate, poultry manure, liquid cattle manure, or liquid swine
      manure. The N sources were surface applied and immediately incorporated at 90 kg
      N ha before seeding of spring wheat ( L.). Cumulative NO-N emissions from the
      silty clay ranged from 2.2 to 8.3 kg ha yr and were slightly lower in the control
      than in the fertilized plots ( = 0.067). The 2-yr mean NO emission factors ranged
      from 2.0 to 4.4% of added N, with no difference among N sources. Emissions of NO
      from the sandy loam soil ranged from 0.3 to 2.2 kg NO-N ha yr, with higher
      emissions with organic than mineral N sources ( = 0.015) and the greatest
      emissions with poultry manure ( < 0.001). The NO emission factor from plots
      amended with poultry manure was 1.8%, more than double that of the other
      treatments (0.3-0.9%), likely because of its high C content. On the silty clay,
      the yield-based NO emissions (g NO-N kg grain yield N) were similar between
      treatments, whereas on the sandy loam, they were greatest when amended with
      poultry manure. Our findings suggest that, compared with mineral N sources,
      manure application only increases soil NO flux in soils with low C content.

PMID- 22370406
TI  - Prediction of odor from pig production based on chemical odorants.
AB  - The present work was performed to investigate the use of odorant measurements for
      prediction of odor concentration in facilities with growing-finishing pigs and to
      analyze the odorant composition in facilities with different floor and
      ventilation systems. Air was sampled in Nalophan bags, odor concentrations were
      measured by dilution-to-threshold olfactometry, and concentrations of odorants
      were measured by proton-transfer-reaction mass spectrometry (PTR-MS).
      Olfactometry and chemical analyses were synchronized to take place at identical
      time intervals after sampling. A principal component analysis revealed that
      different facilities for growing-finishing pigs can be distinguished based on the
      odorants. Pit ventilation comprising a small amount of the total ventilation air
      (10-20%) in facilities with both room and pit ventilation can be used to
      concentrate odorants, whereas the room ventilation contains lower concentrations
      of most odorants. A partial least squares regression model demonstrated that
      prediction of the odor concentration based on odorants measured by PTR-MS is
      feasible. Hydrogen sulfide, methanethiol, trimethylamine, and 4-methylphenol were
      identified as the compounds having the largest influence on the prediction of
      odor concentration, whereas carboxylic acids had no significant influence. In
      conclusion, chemical measurement of odorants by PTR-MS is an alternative for
      expressing the odor concentration in facilities with growing-finishing pigs that
      can be used to increase the understanding of odor from different types of
      facilities and improve the development of odor reduction technologies.

PMID- 22370407
TI  - Intensive cattle grazing affects pasture litter-fall: an unrecognized nitrous
      oxide source.
AB  - The rationale for this study came from observing grazing dairy cattle dropping
      freshly harvested plant material onto the soil surface, hereafter called litter
      fall. The Intergovernmental Panel on Climate Change (IPCC) guidelines include NO
      emissions during pasture renewal but do not consider NO emissions that may result
      from litter-fall. The objectives of this study were to determine litter-fall
      rates and to assess indicative NO emission factors (EFs) for the dominant pasture
      species (perennial ryegrass [ L.] and white clover [ L.]). Herbage was vacuumed
      from intensively managed dairy pastures before and after 30 different grazing
      events when cows (84 cows ha) grazed for 24 h according to a rotational system;
      the interval between grazing events ranged from 21 to 30 d. A laboratory
      incubation study was performed to assess potential EF values for the pasture
      species at two soil moisture contents. Finely ground pasture material was
      incubated under controlled laboratory conditions with soil, and the NO emissions
      were measured until rates returned to control levels. On average, pre- and
      postgrazing dry matter yields per grazing event were 2516 +/- 636 and 1167 +/-
      265 kg DM ha (+/-SD), respectively. Pregrazing litter was absent, whereas
      postgrazing fresh and senesced litter-fall rates were 53 +/- 24 and 19 +/- 18 kg
      DM ha, respectively. Annually, the rotational grazing system resulted in 12
      grazing events where fresh litter-fall equaed to 16 kg N ha yr to the soil.
      Emission factors in the laboratory experiment indicated that the EF for perennial
      ryegrass and white clover ranged from 0.7 to 3.1%. If such EF values should also
      occur under field conditions, then we estimate that litter-fall induces an NO
      emission rate of 0.3 kg NO ha yr. Litter-fall as a source of NO in grazed
      pastures requires further assessment.

PMID- 22370408
TI  - Investigation of carbon tetrachloride destruction by copper acetate.
AB  - Halogenated synthetic organic compounds are used in a wide variety of pesticides,
      solvents, refrigerants, fire retardants, and paints that cause extensive
      pollution to the air, surface water, groundwater, and soils. Carbon tetrachloride
      (CCl) is a typical halogenated synthetic organic compound that has been suspected
      to be toxic and carcinogenic and to cause ozone depletion. In the present work,
      molecular-level destruction of CCl by copper acetate was investigated by extended
      X-ray absorption fine structural spectra, X-ray absorption near-edge spectra, X
      ray photoelectron spectroscopy, and X-ray diffraction spectroscopy.
      Experimentally, the Cl species dissociated from CCl were abstracted by copper
      species and formed CuCl. At 473 to 533 K, reaction products (copper chloride)
      aggregated on the surfaces of CuO, which might cause the obstruction of further
      CCl destruction. Due to the insertion of Cl species into the matrix of CuO, the
      bond distances of Cu-O and Cu-(O)-Cu were increased by 0.3 to 0.4 A and 0.3 to
      0.6 A, respectively. However, at 603 K, because 79.5% of the Cu was in the CCl
      destruction solid products, the coordination number of Cu-(O)-Cu increased to
      5.6. Molecular level investigations are a key to identifying the mechanisms of
      the CCl destruction process. In addition, identification of the molecular
      characteristics of the products may help in safe disposal of the toxic
      substances. The success of this study paved the way for the destruction of
      halogenated organic compounds by copper acetate.

PMID- 22370409
TI  - Water quality characteristics of discharge from reforested loose-dumped mine
      spoil in eastern Kentucky.
AB  - Surface mining is a common method for extracting coal in the coal fields of
      eastern Kentucky. Using the Forestry Reclamation Approach (FRA), which emphasizes
      the use of minimally compacted or loose-dumped spoil as a growth medium for
      trees, reclamation practitioners are successfully reestablishing forests. Yet,
      questions remain regarding the effects FRA has on the quality of waters
      discharged to receiving streams. To examine the effect of FRA on water quality,
      this study compared waters that were discharged from three types of spoils:
      predominantly brown, weathered sandstone (BROWN); predominantly gray, unweathered
      sandstone (GRAY); and an equal mixture of both aforementioned sandstones and
      shale (MIXED). The water quality parameters pH, EC, Ca, K, Mg, Na, NO-N, NH-N,
      SO, Cl, TC, suspended sediment concentration (SSC), settleable solids (SS), and
      turbidity were monitored over a 2-yr period on six 0.4-ha plots (two replications
      per spoil type). Generally, levels of Cl, SO, Ca, NO-N, NH-N, SS, SSC, and
      turbidity decreased over time. The pH for all spoils increased from about 7.5 to
      8.5. The EC remained relatively level in the BROWN spoil, whereas the GRAY and
      MIXED spoils had downward trajectories that were approaching 500 MUS cm. The
      value of 500 MUS cm has been reported as the apparent threshold at which certain
      taxa such as Ephemeroptera (e.g., Mayfly) recolonize disturbed headwater streams
      of eastern Kentucky and adjacent coal-producing Appalachian states.

PMID- 22370410
TI  - Imidacloprid movement in soils and impacts on soil microarthropods in southern
      Appalachian eastern hemlock stands.
AB  - Imidacloprid is a systemic insecticide effective in controlling the exotic pest 
      (hemlock woolly adelgid) in eastern hemlock () trees. Concerns over imidacloprid
      impacts on nontarget species have limited its application in southern Appalachian
      ecosystems. We quantified the movement and adsorption of imidacloprid in forest
      soils after soil injection in two sites at Coweeta Hydrologic Laboratory in
      western North Carolina. Soils differed in profile depth, total carbon and
      nitrogen content, and effective cation exchange capacity. We injected
      imidacloprid 5 cm into mineral soil, 1.5 m from infested trees, using a Kioritz
      soil injector. We tracked the horizontal and vertical movement of imidacloprid by
      collecting soil solution and soil samples at 1 m, 2 m, and at the drip line from
      each tree periodically for 1 yr. Soil solution was collected 20 cm below the
      surface and just above the saprolite, and acetonitrile-extractable imidacloprid
      was determined through the profile. Soil solution and extractable imidacloprid
      concentrations were determined by high-performance liquid chromatography. Soil
      solution and extractable imidacloprid concentrations were greater in the site
      with greater soil organic matter. Imidacloprid moved vertically and horizontally
      in both sites; concentrations generally declined downward in the soil profile,
      but preferential flow paths allowed rapid vertical movement. Horizontal movement
      was limited, and imidacloprid did not move to the tree drip line. We found a
      negative relationship between adsorbed imidacloprid concentrations and soil
      microarthropod populations largely in the low-organic-matter site; however,
      population counts were similar to other studies at Coweeta.

PMID- 22370411
TI  - Regression models for estimating concentrations of atrazine plus deethylatrazine
      in shallow groundwater in agricultural areas of the United States.
AB  - Tobit regression models were developed to predict the summed concentration of
      atrazine [6-chloro--ethyl--(1-methylethyl)-1,3,5-triazine-2,4-diamine] and its
      degradate deethylatrazine [6-chloro--(1-methylethyl)-1,3,5,-triazine-2,4-diamine]
      (DEA) in shallow groundwater underlying agricultural settings across the
      conterminous United States. The models were developed from atrazine and DEA
      concentrations in samples from 1298 wells and explanatory variables that
      represent the source of atrazine and various aspects of the transport and fate of
      atrazine and DEA in the subsurface. One advantage of these newly developed models
      over previous national regression models is that they predict concentrations
      (rather than detection frequency), which can be compared with water quality
      benchmarks. Model results indicate that variability in the concentration of
      atrazine residues (atrazine plus DEA) in groundwater underlying agricultural
      areas is more strongly controlled by the history of atrazine use in relation to
      the timing of recharge (groundwater age) than by processes that control the
      dispersion, adsorption, or degradation of these compounds in the saturated zone.
      Current (1990s) atrazine use was found to be a weak explanatory variable, perhaps
      because it does not represent the use of atrazine at the time of recharge of the
      sampled groundwater and because the likelihood that these compounds will reach
      the water table is affected by other factors operating within the unsaturated
      zone, such as soil characteristics, artificial drainage, and water movement.
      Results show that only about 5% of agricultural areas have greater than a 10%
      probability of exceeding the USEPA maximum contaminant level of 3.0 MUg L. These
      models are not developed for regulatory purposes but rather can be used to (i)
      identify areas of potential concern, (ii) provide conservative estimates of the
      concentrations of atrazine residues in deeper potential drinking water supplies,
      and (iii) set priorities among areas for future groundwater monitoring.

PMID- 22370412
TI  - Latent effect of soil organic matter oxidation on mercury cycling within a
      southern boreal ecosystem.
AB  - The focus of this study is to investigate processes causing the observed spatial
      variation of total mercury (THg) in the soil O horizon of watersheds within the
      Superior National Forest (Minnesota) and to determine if results have
      implications toward understanding long-term changes in THg concentrations for
      resident fish. Principal component analysis was used to evaluate the spatial
      relationships of 42 chemical elements in three soil horizons over 10 watersheds.
      Results indicate that soil organic carbon is the primary factor controlling the
      spatial variation of certain metals (Hg, Tl, Pb, Bi, Cd, Sn, Sb, Cu, and As) in
      the O and A soil horizons. In the B/E horizon, organic carbon appeared to play a
      minor role in metal spatial variation. These characteristics are consistent with
      the concentration of soil organic matter and carbon decreasing from the O to the
      B/E horizons. We also investigated the relationship between percent change in
      upland soil organic content and fish THg concentrations across all watersheds.
      Statistical regression analysis indicates that a 50% reduction in age-one and age
      two fish THg concentration could result from an average 10% decrease in upland
      soil organic content. Disturbances that decrease the content of THg and organic
      matter in the O and A horizons (e.g., fire) may cause a short-term increase in
      atmospherically deposited mercury but, over the long term, may lead to decreased
      fish THg concentrations in affected watersheds.

PMID- 22370413
TI  - The availability of copper in soils historically amended with sewage sludge,
      manure, and compost.
AB  - Metals in soils amended with sewage sludge are typically less available compared
      with those in soils spiked with soluble metal salts. However, it is unclear if
      this difference remains in the long term. A survey of copper (Cu) availability
      was made in soils amended with sewage sludge, manure, and compost, collectively
      named organic amendments. Paired sets of amended and control soils were collected
      from 22 field trials where the organic amendments had aged up to 112 yr. Amended
      soils had higher total Cu concentrations (range, 2-220 mg Cu kg; median, 15 mg Cu
      kg) and organic C (range, 1-16 g kg; median, 4 g kg) than control soils. All
      samples were freshly spiked with CuCl, and the toxicity of added Cu to barley was
      compared between amended and control soils. The toxicity of added Cu was
      significantly lower in amended soils than in control soil in 15 sets by, on
      average, a factor of 1.4, suggesting that aged amendments do not largely increase
      Cu binding sites. The fraction of added Cu that is isotopic exchangeable Cu
      (labile Cu) was compared between control soils freshly spiked with CuCl and
      amended soils with both soils at identical total Cu concentrations. Copper
      derived from amendments was significantly less labile (on average 5.9-fold) than
      freshly added Cu in 18 sets of soils. This study shows that Cu availability after
      long-term applications of organic amendments is lower than that of freshly added
      Cu salts, mainly because of its lower availability in the original matrix and
      ageing reactions than because of increased metal binding sites in soil.

PMID- 22370414
TI  - Fate of pesticides in combined paddy rice-fish pond farming systems in northern
      Vietnam.
AB  - During the last decades, high population growth and export-oriented economics in
      Vietnam have led to a tremendous intensification of rice production, which in
      turn has significantly increased the amount of pesticides applied in rice
      cropping systems. Since pesticides are toxic by design, there is a natural
      concern on the impact of their presence in the environment on human health and
      environmental quality. The present study was designed to examine the water regime
      and fate of pesticides (fenitrothion, dimethoate) during two consecutive rice
      crop seasons in combined paddy rice-fish pond farming systems in northern
      Vietnam. Major results revealed that 5 and 41% (dimethoate), and 1 and 17%
      (fenitrothion) of the applied mass of pesticides were lost from the paddy field
      to the adjacent fish pond during spring and summer crop seasons, respectively.
      The decrease of pesticide concentration in paddy surface water was very rapid
      with dissipation half-life values of 0.3 to 0.8 and 0.2 d for dimethoate and
      fenitrothion, respectively. Key factors controlling the transport of pesticides
      were water solubility and paddy water management parameters, such as hydraulic
      residence time and water holding period. Risk assessment indicates that the
      exposure to toxic levels of pesticides for aquaculture (, ) is significant, at
      least shortly after pesticide application.

PMID- 22370415
TI  - Sorptive and desorptive fractionation of dissolved organic matter by mineral soil
      matrices.
AB  - Interactions of dissolved organic matter (DOM) with soil minerals, such as metal
      oxides and clays, involve various sorption mechanisms and may lead to sorptive
      fractionation of certain organic moieties. While sorption of DOM to soil minerals
      typically involves a degree of irreversibility, it is unclear which structural
      components of DOM correspond to the irreversibly bound fraction and which factors
      may be considered determinants. To assist in elucidating that, the current study
      aimed at investigating fractionation of DOM during sorption and desorption
      processes in soil. Batch DOM sorption and desorption experiments were conducted
      with organic matter poor, alkaline soils. Fourier-transform infrared (FTIR) and
      UV-Vis spectroscopy were used to analyze bulk DOM, sorbed DOM, and desorbed DOM
      fractions. Sorptive fractionation resulted mainly from the preferential uptake of
      aromatic, carboxylic, and phenolic moieties of DOM. Soil metal-oxide content
      positively affected DOM sorption and binding of some specific carboxylate and
      phenolate functional groups. Desorptive fractionation of DOM was expressed by the
      irreversible-binding nature of some carboxylic moieties, whereas other bound
      carboxylic moieties were readily desorbed. Inner-sphere, as opposed to outer
      sphere, ligand-exchange complexation mechanisms may be responsible for these
      irreversible, as opposed to reversible, interactions, respectively. The
      interaction of aliphatic DOM constituents with soil, presumably through weak van
      der Waals forces, was minor and increased with increasing proportion of clay
      minerals in the soil. Revealing the nature of DOM-fractionation processes is of
      great importance to understanding carbon stabilization mechanisms in soils, as
      well as the overall fate of contaminants that might be associated with DOM.

PMID- 22370416
TI  - Microarray assessment of virulence, antibiotic, and heavy metal resistance in an
      agricultural watershed creek.
AB  - Potential risks associated with impaired surface water quality have commonly been
      evaluated by indirect description of potential sources using various fecal
      microbial indicators and derived source-tracking methods. These approaches are
      valuable for assessing and monitoring the impacts of land-use changes and changes
      in management practices at the source of contamination. A more detailed
      evaluation of putative etiologically significant genetic determinants can add
      value to these assessments. We evaluated the utility of using a microarray that
      integrates virulence genes with antibiotic and heavy metal resistance genes to
      describe and discriminate among spatially and seasonally distinct water samples
      from an agricultural watershed creek in Eastern Ontario. Because microarray
      signals may be analyzed as binomial distributions, the significance of ambiguous
      signals can be easily evaluated by using available off-the-shelf software. The
      FAMD software was used to evaluate uncertainties in the signal data. Analysis of
      multilocus fingerprinting data sets containing missing data has shown that, for
      the tested system, any variability in microarray signals had a marginal effect on
      data interpretation. For the tested watershed, results suggest that in general
      the wet fall season increased the downstream detection of virulence and
      resistance genes. Thus, the tested microarray technique has the potential to
      rapidly describe the quality of surface waters and thus to provide a qualitative
      tool to augment quantitative microbial risk assessments.

PMID- 22370417
TI  - A simple model to assess nitrogen and phosphorus contamination in ungauged
      surface drainage networks: application to the Massaciuccoli Lake Catchment,
      Italy.
AB  - Modeling is a common practice to evaluate factors affecting water quality in
      environmental systems impaired by point and nonpoint losses of N and P.
      Nevertheless, in situations with inadequate information, such as ungauged basins,
      a balance between model complexity and data availability is necessary. In this
      paper, we applied a simplified analytical model to an artificially drained
      floodplain in central-western Italy to evaluate the importance of different
      nutrient sources and in-stream retention processes and to identify critical
      source areas. We first considered only a set of chemical concentrations in water
      measured from February through May 2008 and from November 2008 through February
      2009. We then broadened available data to include water discharge and hydraulic
      head measurements to construct a hydrogeological model using MODFLOW-2000 and to
      evaluate the reliability of the simplified method. The simplified model provided
      acceptable estimates of discharge (ranging from 0.03-0.75 m s) and diffuse
      nutrient inputs from water table discharge and in-stream retention phenomena.
      Estimates of PO-P and total P retention (ranging from 1.0 to 0.6 MUg m s and from
      1.18 to 0.95 MUg m s for PO-P and total P, respectively) were consistent with the
      range of variability in literature data. In contrast, the higher temporal
      variability of nitrate concentrations decreased model accuracy, suggesting the
      need for more intensive monitoring. The model also separated the dynamics of
      different reaches of the drainage network and identified zones considered
      critical source areas and buffer zones where pollutant transport is reduced.

PMID- 22370418
TI  - Water quality, sediment, and soil characteristics near Fargo-Moorhead urban areas
      as affected by major flooding of the Red River of the North.
AB  - Spring flooding of the Red River of the North (RR) is common, but little
      information exits on how these flood events affect water and overbank sediment
      quality within an urban area. With the threat of the spring 2009 flood in the RR
      predicted to be the largest in recorded history and the concerns about the
      flooding of farmsteads, outbuildings, garages, and basements, the objectives of
      this study, which focused on Fargo, ND, and Moorhead, MN, were to assess
      floodwater quality and to determine the quantity and quality of overbank sediment
      deposited after floodwaters recede and the quality of soil underlying sediment
      deposits. 17beta-Estradiol was detected in 9 of 24 water samples, with an average
      concentration of 0.61 ng L. Diesel-range organics were detected in 8 of 24
      samples, with an average concentration of 80.0 MUg L. The deposition of sediment
      across locations and transects ranged from 2 to 10 kg m, and the greatest mass
      deposition of chemicals was closest to the river channel. No gasoline-range
      organics were detected, but diesel-range organics were detected in 26 of the 27
      overbank sediment samples (maximum concentration, 49.2 mg kg). All trace elements
      detected in the overbank sediments were within ranges for noncontaminated sites.
      Although flooding has economic, social, and environmental impacts, based on the
      results of this study, it does not appear that flooding in the RR in F-M led to
      decreased quality of water, sediment, or soil compared with normal river flows or
      resident soil.

PMID- 22370419
TI  - Soil property control of biogeochemical processes beneath two subtropical
      stormwater infiltration basins.
AB  - Substantially different biogeochemical processes affecting nitrogen fate and
      transport were observed beneath two stormwater infiltration basins in north
      central Florida. Differences are related to soil textural properties that deeply
      link hydroclimatic conditions with soil moisture variations in a humid,
      subtropical climate. During 2008, shallow groundwater beneath the basin with
      predominantly clayey soils (median, 41% silt+clay) exhibited decreases in
      dissolved oxygen from 3.8 to 0.1 mg L and decreases in nitrate nitrogen (NO-N)
      from 2.7 mg L to <0.016 mg L, followed by manganese and iron reduction, sulfate
      reduction, and methanogenesis. In contrast, beneath the basin with predominantly
      sandy soils (median, 2% silt+clay), aerobic conditions persisted from 2007
      through 2009 (dissolved oxygen, 5.0-7.8 mg L), resulting in NO-N of 1.3 to 3.3 mg
      L in shallow groundwater. Enrichment of deltaN and deltaO of NO combined with
      water chemistry data indicates denitrification beneath the clayey basin and
      relatively conservative NO transport beneath the sandy basin. Soil-extractable NO
      N was significantly lower and the copper-containing nitrite reductase gene
      density was significantly higher beneath the clayey basin. Differences in
      moisture retention capacity between fine- and coarse-textured soils resulted in
      median volumetric gas-phase contents of 0.04 beneath the clayey basin and 0.19
      beneath the sandy basin, inhibiting surface/subsurface oxygen exchange beneath
      the clayey basin. Results can inform development of soil amendments to maintain
      elevated moisture content in shallow soils of stormwater infiltration basins,
      which can be incorporated in improved best management practices to mitigate NO
      impacts.

PMID- 22370420
TI  - Precision placement of separated dairy sludge improves early phosphorus nutrition
      and growth in corn ( L.).
AB  - Efficient use of manure nutrients by crops is necessary to minimize losses to the
      environment. This field study examined the possibility of replacing side-banded
      mineral P with precision-placed high-P sludge (6.2-11.0% dry matter) obtained
      after settling dairy manure slurry. The sludge was injected at about 30 kg P ha
      (36.0-51.2 m ha) into the soil at corn row spacing, and the corn was planted 5,
      10, and 15 cm beside the injection furrow. Controls included no added P and side
      banded commercial P fertilizer. The treatments were tested on corn with low and
      high root colonization by arbuscular mycorrhizae (AM). The study showed that
      sludge did not impede AM root colonization, corn germination, or seedling growth.
      Corn plants with both high and low levels of AM colonization responded to the
      sludge from the three-leaf stage and showed the greatest benefit at the six-leaf
      stage. Corn responded more to sludge placed at 5 than at 15 cm from the corn
      rows, whereas the response at the 10-cm spacing was intermediate. There was
      little difference in seedling growth or final harvest parameters between the side
      banded fertilizer P and the 5-cm sludge treatment. The results show a new way to
      use manure nutrients, namely precision-placement sludge for corn. This may
      obviate the need for chemical fertilizers for improving farm nutrient balances.
      Other anticipated benefits are less energy use for hauling and injection of the
      sludge fraction and reduced risk of nutrient loss by runoff and volatilization
      (ammonia) and nuisance odors due to injection.

PMID- 22370421
TI  - Field application of farmstead runoff to vegetated filter strips: surface and
      subsurface water quality assessment.
AB  - Farmstead runoff poses significant environmental impacts to ground and surface
      waters. Three vegetated filter strips were assessed for the treatment of dairy
      farmstead runoff at the soil surface and subsurface at 0.3- or 0. 46-m and 0. 76
      m depths for numerous storm events. A medium-sized Michigan dairy was retrofitted
      with two filter strips on sandy loam soil and a third filter strip was
      implemented on a small Michigan dairy with sandy soil to collect and treat runoff
      from feed storage, manure storage, and other impervious farmstead areas. All
      filter strips were able to eliminate surface runoff via infiltration for all
      storm events over the duration of the study, eliminating pollutant contributions
      to surface water. Subsurface effluent was monitored to determine the contributing
      groundwater concentrations of numerous pollutants including chemical oxygen
      demand (COD), metals, and nitrates. Subsurface samples have an average reduction
      of COD concentrations of 20, 11, and 85% for the medium dairy Filter Strip 1
      (FS1), medium dairy Filter Strip 2 (FS2), and the small Michigan dairy
      respectively, resulting in average subsurface concentrations of 355, 3960, and
      718 mg L COD. Similar reductions were noted for ammonia and total Kjeldahl
      nitrogen (TKN) in the subsurface effluent. The small Michigan dairy was able to
      reduce the pollutant leachate concentrations of COD, TKN, and ammonia over a
      range of influent concentrations. Increased influent concentrations in the medium
      Michigan dairy filter strips resulted in an increase in COD, TKN, and ammonia
      concentrations in the leachate. Manganese was leached from the native soils at
      all filter strips as evidenced by the increase in manganese concentrations in the
      leachate. Nitrate concentrations were above standard drinking water limits (10 mg
      L), averaging subsurface concentrations of 11, 45, and 25 mg L NO-N for FS1, FS2,
      and the small Michigan dairy, respectively.

PMID- 22370422
TI  - Inundation influences on bioavailability of phosphorus in managed wetland
      sediments in agricultural landscapes.
AB  - Agricultural runoff carries high nutrient loads to receiving waters, contributing
      to eutrophication. Managed wetlands can be used in integrated management efforts
      to intercept nutrients before they enter downstream aquatic systems, but detailed
      information regarding sorption and desorption of P by wetland sediments during
      typical inundation cycles is lacking. This study seeks to quantify and elucidate
      how inundation of wetland sediments affects bioavailability of P and
      contributions of P to downstream systems. A managed wetland cell in Tunica
      County, Mississippi was subjected to a simulated agricultural runoff event and
      was monitored for bioavailable phosphorus (water-extractable P [P], Fe-P, and Al
      P) of wetland sediments and water level during the runoff event and for 130 d
      afterward. Inundation varied longitudinally within the wetland, with data
      supporting significant temporal relationships between inundation and P
      desorption. Concentrations of P were significantly higher at the site that
      exhibited variable hydroperiods (100 m) as compared with sites under consistent
      inundation. This suggests that sites that are inundated for longer periods of
      time desorb less P immediately to the environment than sites that have periodic
      or ephemeral inundation. Concentrations of iron oxalate and NaOH-P were
      significantly higher at the least inundated site as compared with all other sites
      (F = 5.43;  = 0.001) irrespective of time. These results support the hypothesis
      that increased hydraulic residence time decreases the bioavailability of P in
      wetland sediments receiving agricultural runoff. This finding suggests that the
      restoration of wetlands in the mid-southern United States may be hydrologically
      managed to improve P retention.

PMID- 22370427
TI  - Antiresorptive therapies in oncology and their effects on cancer progression.
AB  - Bone health is an emerging concern in the early breast cancer setting. Current
      adjuvant therapies, especially hormonal therapies in premenopausal patients (e.g.
      goserelin) and aromatase inhibitors in postmenopausal patients, have been
      associated with substantial decreases in bone mineral density that may place
      patients at risk for fractures. Bisphosphonates--and the recently approved anti
      RANKL antibody, denosumab--have both demonstrated activity for the treatment of
      postmenopausal osteoporosis and cancer treatment-induced bone loss (CTIBL) in
      breast cancer patients, although neither has received widespread approval
      specifically for CTIBL. However, some bisphosphonates, especially the nitrogen
      containing bisphosphonate zoledronic acid, have also demonstrated clinically
      meaningful anticancer effects in patients receiving adjuvant hormonal therapy for
      breast cancer and in other oncology settings. The effects of denosumab on cancer
      disease outcomes in the adjuvant setting remain to be established. This
      discrepancy has created a dilemma in terms of how to evaluate the complete
      benefit:risk profile of bone-health management options in the adjuvant breast
      cancer setting. This review summarises the current data on the course of cancer
      in clinical trials of the antiresorptive agents and provides important insight
      into the relative anticancer potential of the various therapies.

PMID- 22370428
TI  - New and improved methods for measuring lymphocyte proliferation in vitro and in
      vivo using CFSE-like fluorescent dyes.
AB  - The use of carboxyfluorescein diacetate succinimidyl ester (CFSE) to measure
      lymphocyte proliferation by flow cytometry has become one of the most widely
      utilised assays for assessing lymphocyte responses. The properties of CFSE make
      it ideal for such a task, covalently labelling cells with a long-lived
      fluorescence of high intensity and low variance with minimal cell toxicity. No
      dye in the last 20 years has been capable of replicating CFSE in these respects.
      However, currently CFSE is limited to following a maximum of 7 cell divisions and
      is not compatible for use with ubiquitously available fluorescein conjugates or
      other fluorescent molecules with spectral properties similar to fluorescein, such
      as EGFP. Here we characterise two new fluorescent dyes for measuring lymphocyte
      proliferation, Cell Trace Violet (CTV) and Cell Proliferation Dye eFluor 670
      (CPD), which have different excitation and emission spectra to CFSE and,
      consequently, are compatible with fluorescein conjugates. We found that while
      both CTV and CPD can label cells to a high fluorescence intensity, which is long
      lived and has low variability and low toxicity and makes them ideal for long-term
      tracking of non-dividing lymphocytes in vivo, CTV offers possibly the best
      available alternative to CFSE in the analysis of cell divisions. We also describe
      how intercellular dye transfer and cell autofluorescence can affect division
      resolution with the three different dyes and describe labelling conditions for
      the three dyes that produce ultra-bright lymphocytes for in vivo tracking studies
      and allow up to 11 cell divisions to be detected when using CFSE and CTV as the
      fluorescent dyes.

PMID- 22370429
TI  - Single molecule enzyme-linked immunosorbent assays: theoretical considerations.
AB  - We have developed a highly sensitive immunoassay-called digital ELISA-that is
      based on the detection of single enzyme-linked immunocomplexes on beads that are
      sealed in arrays of femtoliter wells. Digital ELISA was designed to be highly
      efficient in the capturing of target proteins, labeling of these proteins, and
      their detection in single molecule arrays (SiMoA); in essence, the goal of the
      assay is to "capture every molecule, detect every molecule". Here we provide the
      theoretical basis for the design of this assay derived from simple equations
      based on bimolecular interactions. Using these equations and knowledge of the
      concentrations of reagents, the times of interactions, and the on- and off-rates
      of the molecular interactions for each step of the assay, it is possible to
      predict the number of immunocomplexes that are formed and detected by SiMoA. The
      unique ability of SiMoA to count single immunocomplexes and determine an average
      number of enzymes per bead (AEB), makes it possible to directly compare the
      number of molecules detected experimentally to those predicted by theory. These
      predictions compare favorably to experimental data generated for a digital ELISA
      for prostate specific antigen (PSA). The digital ELISA process is efficient
      across a range of antibody affinities (K(D)~10(-11) -10(-9) M), and antibodies
      with high on-rates (k(on)>10(5) M(-1) s(-1)) are predicted to perform best. The
      high efficiency of digital ELISA and sensitivity of SiMoA to enzyme label also
      makes it possible to reduce the concentration of labeling reagent, reduce
      backgrounds, and increasing the specificity of the approach. Strategies for
      dealing with the dissociation of antibody complexes over time that can affect the
      signals in an assay are also described.

PMID- 22370430
TI  - Development of monoclonal antibodies and ELISA specific for the mouse vascular
      endocan.
AB  - Human vascular endocan is a proteoglycan exhibiting tumorigenic activity through
      both its glycan and protein cores. Endocan mRNA is identified as being one of the
      most significant molecular signatures defining a poor prognosis in lung, breast,
      kidney, prostate, and thyroid malignancies. The survival inversely correlates
      with endocan expression in tumor tissue from hepatocarcinoma, and in serum from
      lung cancer. In mouse, endocan mRNA is also increased in tumor vessels. However,
      mouse endocan has not yet been fully characterized. Here, we produced a panel of
      rat monoclonal antibodies directed against mouse endocan, leading to the
      development of a specific mouse/rat endocan ELISA. Mouse endocan serum level was
      measured at a median of 0.96 ng/mL and 1.08 ng/mL in 129Sv mice and C57bl6,
      respectively. These results also provide new tools to characterize and explore
      the role of endocan in mouse and rat models of human diseases. These results
      present mouse vascular endocan as a circulating molecule similar to human
      endocan.

PMID- 22370431
TI  - Health-related quality of life among heavy-drinking college students.
AB  - OBJECTIVE: To examine unique contributions of depression, alcohol consumption,
      and alcohol-related consequences on functional health outcomes in college
      students. METHODS: Participants were heavy-drinking undergraduate students (N =
      207) who completed self-report questionnaires. RESULTS: For men and women,
      depression predicted overall general health and mental health ratings. For women,
      depression predicted number of days of role limitations due to poor physical or
      mental health and number of days of not getting enough sleep or rest.
      CONCLUSIONS: Findings  suggest that depression may have a more pervasive
      association with HRQOL than alcohol misuse or alcohol-related consequences in
      college students.

PMID- 22370432
TI  - Alternative high school students' physical activity: role of self-efficacy.
AB  - OBJECTIVE: To examine physical activity self-efficacy as a mediator of the
      association between perceived barriers to PA and moderate-to-vigorous physical
      activity (MVPA) among alternative high school (AHS) students. METHODS: Students
      (N=145) from 6 AHS completed self-report  questionnaires. RESULTS: Mediation
      analyses revealed partial mediation of PA self-efficacy on relationships between
      general barriers to PA and MVPA (b = -.39 reduced b = -.33) among females (47.6%
      of sample). CONCLUSIONS: Interventions with female AHS students should  include a
      component on building PA self-efficacy. However, results suggest the broader
      environment may have greater impact on MVPA than individual-level psycho-social
      factors.

PMID- 22370433
TI  - Scale development: perceived barriers to public use of school recreational
      facilities.
AB  - OBJECTIVES: To test an original scale assessing perceived barriers among school
      administrators to allowing community use of school recreational facilities
      outside of regular school hours. METHODS: Exploratory factor analysis (EFA) and
      confirmatory factor analysis (CFA). RESULTS: Using EFA and CFA, we found that a
      model including factors of legal/security, resources, and social support
      demonstrated the best relative fit for our data. CONCLUSIONS: The Perceived
      Barriers to Community Use (PBCU) Scale is psychometrically sound and provides a
      framework  to guide the design of future research and discussion of perceived
      barriers that school administrators have about opening their school recreational
      facilities outside of regular school hours.

PMID- 22370434
TI  - The better weight-better sleep study: a pilot intervention in primary care.
AB  - OBJECTIVE: To explore the feasibility of integrating sleep management
      interventions with dietary and exercise interventions for obesity in a 12-week
      randomized trial. METHODS: We randomized 49 overweight or obese adult patients
      either to a better weight (BW) cognitive  behavioral intervention, or to a
      combination of the BW intervention and a better sleep intervention, better weight
      better sleep (BWBS). RESULTS: The BWBS group lost weight faster (P=.04), and
      coping self-efficacy accelerated (P=.01). CONCLUSIONS: These preliminary results
      merit  replication in a larger primary care-based trial with a longer continuous
      intervention and follow-up period.

PMID- 22370436
TI  - High-risk HIV minorities in the United States: who gets tested and where?
AB  - OBJECTIVES: To assess characteristics of high-risk populations tested for HIV at
      particular testing sites. METHODS: BRFSS data (N=20,633) was used to quantify
      rates of HIV testing and identify specific racial/ethnic testing locations.
      RESULTS: Analysis determined  associations existing among high-risk individuals
      based on demographics. Testing differences were identified in racial/ ethnic
      groups among those at high-risk in the United States. HIV testing was more likely
      among high-risk African Americans (OR=1.62), other races (OR=1.42), and
      multiracial  participants (OR=1.89) than whites. CONCLUSIONS: Minorities were
      more likely to be tested at locations such as hospitals and clinics supporting
      the need for alternative testing locations.

PMID- 22370435
TI  - Formative research for a community-based message-framing intervention.
AB  - OBJECTIVE: To inform a community-based message framing intervention encouraging
      physical activity and fruit and vegetable consumption among medically underserved
      adults. METHOD: Key informant interviews, focus groups, and a survey were
      conducted with limited-literacy Hispanics  in the northeastern United States.
      RESULTS: Barriers to healthy lifestyle behaviors exist at individual, community,
      and policy levels. A strong degree of networking among local organizations and
      elected officials exists that can be used to encourage healthy lifestyle
      initiatives. CONCLUSIONS: Community-based health communication interventions must
      address neighborhood realities, the literacy levels of the target population, and
      existing networks of providers and consumers.

PMID- 22370437
TI  - Spiritual health locus of control and health behaviors in African Americans.
AB  - OBJECTIVE: To examine relationships between spiritual health locus of control
      beliefs and various health behaviors. METHODS: A cross-sectional survey of a
      national sample of African Americans assessed spiritual beliefs, fruit and
      vegetable consumption, physical activity,  and alcohol consumption. RESULTS:
      Active spiritual beliefs were positively associated with fruit consumption and
      negatively associated with alcohol consumption. Passive spiritual beliefs were
      associated with lower vegetable and increased alcohol consumption. Among male
      participants,  passive spiritual beliefs were associated with higher alcohol
      consumption. CONCLUSIONS: Findings suggest that dimensions of spiritual health
      locus of control beliefs have complex and varying relationships with health
      behaviors.

PMID- 22370438
TI  - Perceptions of smoking cessation programs in rural Appalachia.
AB  - OBJECTIVES: To identify perspectives on smoking cessation programs in Appalachian
      Kentucky, a region with particularly high smoking rates and poor health outcomes.
      METHODS: Insufficient existing research led us to conduct 12 focus groups
      (smokers and nonsmokers) and 23  key informant interviews. RESULTS: Several
      findings previously not described in this high-risk population include (1)
      transition from pro-tobacco culture toward advocacy for tobacco cessation
      approaches, (2) region-specific challenges to program access, and (3) strong and
      diverse social  influences on cessation. CONCLUSIONS: To capitalize on changes
      from resistance to support for smoking cessation, leaders should incorporate
      culturally appropriate programs and characteristics identified here.

PMID- 22370439
TI  - Longitudinal change in physical activity and disability in adults.
AB  - OBJECTIVES: To prospectively examine whether physical activity or change in
      physical activity increases or decreases the risk of disability later in life.
      METHODS: Tobit regression models were used to examine the effect of physical
      activity at baseline and change from  baseline on disability 10 and 20 years
      later in 6913 adults. RESULTS: Increasing recreational physical activity was
      associated with reduced risk of disability whereas reducing recreational physical
      activity increased the risk of disability after 10 years. CONCLUSIONS: The
      analyses  reveal a protective effect of sustained physical activity on disability
      among adults.

PMID- 22370441
TI  - Associations between adverse childhood experiences, psychological distress, and
      adult alcohol problems.
AB  - OBJECTIVE: To examine the mediating role of psychological distress on the
      relationship between adverse childhood experiences and adult alcohol problems by
      gender. METHODS: Linear and logistic regression analyses were conducted on 7279
      Kaiser-Permanente members, aged >18  years. RESULTS: Psychological distress
      mediated significant proportions of alcohol problems associated with childhood
      emotional abuse and neglect, physical abuse and neglect, mental illness in the
      household, parental separation or divorce, sexual abuse, and household drug use
      among  women and mental illness in the household, emotional neglect, physical
      abuse, household drug use, and sexual abuse among men. CONCLUSION: It may be
      important to identify early childhood trauma and adult psychological distress in
      programs that focus on reducing alcohol abuse.

PMID- 22370440
TI  - Psychosocial correlates of weight maintenance among black & white adults.
AB  - OBJECTIVES: To investigate (1) weight maintenance among black and white
      participants and (2) psychosocial correlates (eg, healthy eating barriers, self
      efficacy, stress) of weight maintenance 18 months after behavioral weight-loss
      treatment. METHODS: Linear and logistic  regression examined weight change and
      unsuccessful weight maintenance (>5% weight gain) among 107 black and white
      adults. RESULTS: After controlling for socio-demographics, differences in weight
      maintenance between ethnicities were not generally noted. Healthy eating barriers
      and  stressful life events were associated with weight gain, P<.04. CONCLUSIONS:
      Strategies to cope with stressful events and overcome barriers to eating
      healthfully are needed for weight maintenance among both ethnicities.

PMID- 22370442
TI  - Knowledge, attitudes, and behavior concerning nutrition and physical activity in
      Mexican children.
AB  - OBJECTIVE: To identify the stages of behavior change and the knowledge,
      attitudes, and habits concerning nutrition and physical activity in Mexican
      children. METHODS: A survey was applied to 48 children from 10 years old to
      obtain data. Stages of behavior change were classified  according to the
      transtheoretical model. RESULTS: For food habits, 31% were in precontemplation,
      17% in contemplation, 10% in preparation, 40% in action, and 2% in maintenance.
      For physical activity, 12% were in precontemplation, 15% in contemplation, 29% in
      preparation, 42% in action,  and 2% in maintenance. CONCLUSIONS: It is important
      to consider the stages of behavior change to plan strategies of educational
      models.

PMID- 22370443
TI  - Tetragonal zirconia spheres fabricated by carbon-assisted selective laser heating
      in a liquid medium.
AB  - Submicrometer-sized tetragonal zirconia spheres are synthesized by carbon
      assisted selective pulsed laser heating in a liquid medium at room temperature.
      Sphere formation and phase transformation from the monoclinic to the tetragonal
      phase are only observed by laser irradiation of a colloidal solution containing
      raw zirconia mechanically milled with nanocarbon. This result indicates that
      nanocarbon, having close contact with zirconia particles, plays a very important
      role in forming submicrometer-sized tetragonal zirconia spheres.

PMID- 22370444
TI  - Effects of a wheat bran extract containing arabinoxylan oligosaccharides on
      gastrointestinal health parameters in healthy adult human volunteers: a double
      blind, randomised, placebo-controlled, cross-over trial.
AB  - Wheat bran extract (WBE) is a food-grade soluble fibre preparation that is highly
      enriched in arabinoxylan oligosaccharides. In this placebo-controlled cross-over
      human intervention trial, tolerance and effects on colonic protein and
      carbohydrate fermentation were studied. After a 1-week run-in period, sixty-three
      healthy adult volunteers consumed 3, 10 and 0 g WBE/d for 3 weeks in a random
      order, with 2 weeks' washout between each treatment period. Fasting blood samples
      were collected at the end of the run-in period and at the end of each treatment
      period for analysis of haematological and clinical chemistry parameters.
      Additionally, subjects collected a stool sample for analysis of microbiota, SCFA
      and pH. A urine sample, collected over 48 h, was used for analysis of p-cresol
      and phenol content. Finally, the subjects completed questionnaires scoring
      occurrence frequency and distress severity of eighteen gastrointestinal symptoms.
      Urinary p-cresol excretion was significantly decreased after WBE consumption at
      10 g/d. Faecal bifidobacteria levels were significantly increased after daily
      intake of 10 g WBE. Additionally, WBE intake at 10 g/d increased faecal SCFA
      concentrations and lowered faecal pH, indicating increased colonic fermentation
      of WBE into desired metabolites. At 10 g/d, WBE caused a mild increase in
      flatulence occurrence frequency and distress severity and a tendency for a mild
      decrease in constipation occurrence frequency. In conclusion, WBE is well
      tolerated at doses up to 10 g/d in healthy adults volunteers. Intake of 10 g
      WBE/d exerts beneficial effects on gut health parameters.

PMID- 22370445
TI  - Deciduous molar hypomineralization and molar incisor hypomineralization.
AB  - This study was embedded in the Generation R Study, a population-based prospective
      cohort study from fetal life until young adulthood. This study focused on the
      relationship between Deciduous Molar Hypomineralization (DMH) and Molar Incisor
      Hypomineralization (MIH). First permanent molars develop during a period similar
      to that of second primary molars, with possible comparable risk factors for
      hypomineralization. Children with DMH have a greater risk of developing MIH.
      Clinical photographs of clean, moist teeth were taken with an intra-oral camera
      in 6,161 children (49.8% girls; mean age 74.3 mos, SD +/- 5.8). First permanent
      molars and second primary molars were scored with respect to DMH or MIH. The
      prevalence of DMH and MIH was 9.0% and 8.7% at child level, and 4.0% and 5.4% at
      tooth level. The Odds Ratio for MIH based on DMH was 4.4 (95% CI, 3.1-6.4). The
      relationship between the occurrence of DMH and MIH suggests a shared cause and
      indicates that, clinically, DMH can be used as a predictor for MIH.

PMID- 22370447
TI  - Engineering endostatin-expressing cartilaginous constructs using injectable
      biopolymer hydrogels.
AB  - The release of an anti-angiogenic agent, such as type XVIII/endostatin, from an
      implantable scaffold may be of benefit in the repair of articular cartilage. The
      objectives of this study are to develop an injectable mesenchymal stem cell (MSC)
      incorporating collagen-based hydrogel capable of undergoing covalent cross
      linking in vivo and overexpressing endostatin using nonviral transfection, and to
      investigate methods for the retention of the endostatin protein within the
      scaffolds. The effects of different cross-linking agents (genipin,
      transglutaminase-2, and microbial transglutaminase) and different binding
      molecules for endostatin retention (heparin, heparan sulfate, and chondroitin
      sulfate) are evaluated. Cartilaginous constructs that overexpress endostatin for
      3 weeks are successfully engineered. Most of the endostatin is released into the
      surrounding media and is not retained within the constructs. The presence of two
      common basement membrane molecules, laminin and type IV collagen, which have been
      reported in developing and mature articular cartilage and are generally
      associated with type XVIII collagen in vivo, is also observed in the engineered
      cartilaginous constructs. Endostatin-producing cartilaginous constructs can be
      formulated by growing nonvirally transfected mesenchymal stem cells in collagen
      gels covalently cross-linked using genipin, transglutaminase-2, and microbial
      transglutaminase. These constructs warrant further investigation for cartilage
      repair procedures. The novel finding of laminin and type IV collagen in the
      engineered cartilage constructs may be of importance for future work toward
      understanding the role of basement membrane molecules in chondrogenesis and in
      the physiology and pathology of articular cartilage.

PMID- 22370446
TI  - Association of AXIN2 with non-syndromic oral clefts in multiple populations.
AB  - We have previously shown the association of AXIN2 with oral clefts in a US
      population. Here, we expanded our study to explore the association of 11 AXIN2
      markers in 682 cleft families from multiple populations. Alleles for each AXIN2
      marker were tested for transmission distortion with clefts by means of the Family
      based Association Test. We observed an association with SNP rs7224837 and all
      clefts in the combined populations (p = 0.001), and with SNP rs3923086 and cleft
      lip and palate in Asian populations (p = 0.004). We confirmed our association
      findings in an additional 528 cleft families from the United States (p < 0.009).
      We tested for gene-gene interaction between AXIN2 and additional cleft
      susceptibility loci. We assessed and detected Axin2 mRNA and protein expression
      during murine palatogenesis. In addition, we also observed co-localization of
      Axin2 with Irf6 proteins, particularly in the epithelium. Our results continue to
      support a role for AXIN2 in the etiology of human clefting. Additional studies
      should be performed to improve our understanding of the biological mechanisms
      linking AXIN2 to oral clefts.

PMID- 22370448
TI  - A linear-dendritic cationic vector for efficient DNA grasp and delivery.
AB  - This paper presents an attempt to design an efficient and biocompatible cationic
      gene vector via structural optimization that favors the efficient utilization of
      amine groups for DNA condensation. To this end, a linear-dendritic block
      copolymer of methoxyl-poly(ethylene glycol)-dendritic polyglycerol-graft-tris(2
      aminoethyl)amine (mPEG-DPG-g-TAEA) was prepared with specially designed multiple
      functions including strong DNA affinity, endosomal buffering and expected serum
      tolerance. Based on the transfection in serum-free and serum-conditioned media,
      the influences of the polymer structures including the degree of polymerization
      of DPG and TAEA substitution degree were explored. As compared to
      polyethylenimine (M(w)=5 kDa) (PEI5k) with similar molecular weight and higher
      amine density, mPEG-DPG-g-TAEA displayed comparably high DNA affinity due to the
      special linear-dendritic architecture. Consequently, at very low N/P ratio, mPEG
      DPG-g-TAEA vectors could mediate efficient in vitro luciferase expression at
      levels that are comparable with or even superior to the commercially available
      LipofectamineTM 2000, while being apparently higher than PEI5k. The designed
      vectors exhibit considerably higher cell biocompatibility and better resistance
      against bovine serum albumin adsorption than PEI5k. The stability of the
      complexes on coincubation with heparin was found to be largely dependent on the
      polymer structure. As concluded from the comparative transfection study in the
      absence/presence of chloroquine, it is likely that the polycation itself could
      produce endosomal buffering. This linear-dendritic vector shows promising
      potential for the application of gene delivery.

PMID- 22370450
TI  - Fungemia caused by non-Candida species.

PMID- 22370451
TI  - Biotechnology for a more sustainable environment decontamination and energy
      production.

PMID- 22370449
TI  - Regulation of plasma cholesterol esterification by sphingomyelin: effect of
      physiological variations of plasma sphingomyelin on lecithin-cholesterol
      acyltransferase activity.
AB  - Although sphingomyelin (SM) is the most abundant phospholipid in the plasma, next
      to phosphatidylcholine (PC), its physiological function in plasma is unclear.
      Here we employed plasma from various genetic models of mice which naturally
      differ in their plasma SM/PC ratios, to study the role of SM as a modulator of
      LCAT, the enzyme responsible for HDL maturation and the synthesis of cholesteryl
      esters (CE) in normal plasma. Serine palmitoyltransferase deficient mice, and SM
      synthase deficient mice, both of which have below normal SM/PC ratios, showed
      significantly elevated LCAT activities when assayed with the endogenous
      substrates. On the other hand, LDL receptor knockout mice, and apo E knockout
      mice, both of which have high SM/PC ratios, had markedly reduced (-80%) LCAT
      activities. The LCAT levels in plasma, as assayed with an exogenous substrate,
      were similar in all groups, except for a 45% decrease in apo E knockout mice.
      Plasma samples with high SM/PC ratios had lower percentage of 20:4, 22:5, and
      22:6 CE all of which are formed by LCAT, and a higher percentage of the
      atherogenic 18:1 CE which is mainly derived from the action of liver ACAT,
      showing that in vivo, the contribution of LCAT to plasma CE is reduced while that
      of liver ACAT is increased. These results show that SM is a physiological
      modulator of LCAT activity as well as plasma CE composition, and this may
      contribute to the previously reported pro-atherogenic effect of high plasma SM
      levels.

PMID- 22370454
TI  - Experimental arthritis: A new co-therapeutic strategy for RA?

PMID- 22370452
TI  - De-identification methods for open health data: the case of the Heritage Health
      Prize claims dataset.
AB  - BACKGROUND: There are many benefits to open datasets. However, privacy concerns
      have hampered the widespread creation of open health data. There is a dearth of
      documented methods and case studies for the creation of public-use health data.
      We describe a new methodology for creating a longitudinal public health dataset
      in the context of the Heritage Health Prize (HHP). The HHP is a global data
      mining competition to predict, by using claims data, the number of days patients
      will be hospitalized in a subsequent year. The winner will be the team or
      individual with the most accurate model past a threshold accuracy, and will
      receive a US $3 million cash prize. HHP began on April 4, 2011, and ends on April
      3, 2013. OBJECTIVE: To de-identify the claims data used in the HHP competition
      and ensure that it meets the requirements in the US Health Insurance Portability
      and Accountability Act (HIPAA) Privacy Rule. METHODS: We defined a threshold risk
      consistent with the HIPAA Privacy Rule Safe Harbor standard for disclosing the
      competition dataset. Three plausible re-identification attacks that can be
      executed on these data were identified. For each attack the re-identification
      probability was evaluated. If it was deemed too high then a new de-identification
      algorithm was applied to reduce the risk to an acceptable level. We performed an
      actual evaluation of re-identification risk using simulated attacks and matching
      experiments to confirm the results of the de-identification and to test
      sensitivity to assumptions. The main metric used to evaluate re-identification
      risk was the probability that a record in the HHP data can be re-identified given
      an attempted attack. RESULTS: An evaluation of the de-identified dataset
      estimated that the probability of re-identifying an individual was .0084, below
      the .05 probability threshold specified for the competition. The risk was robust
      to violations of our initial assumptions. CONCLUSIONS: It was possible to ensure
      that the probability of re-identification for a large longitudinal dataset was
      acceptably low when it was released for a global user community in support of an
      analytics competition. This is an example of, and methodology for, achieving open
      data principles for longitudinal health data.

PMID- 22370458
TI  - Pediatric rheumatic disease: Treating lupus nephritis in children--is there a
      gold standard?

PMID- 22370459
TI  - Experimental arthritis: Effects of MSCs in spontaneous OA.

PMID- 22370460
TI  - Fatigue and cognitive symptoms in patients with diabetes: relationship with
      disease phenotype and insulin treatment.
AB  - Neurobehavioral symptoms are frequently reported in patients with diabetes.
      Nevertheless, the characterization of the specific symptom dimensions that
      develop in diabetic patients with respect to disease phenotype and treatment
      status remains obscure. This study comparatively assessed fatigue symptoms and
      cognitive performance using a dimensional approach in 21 patients with insulin
      treated type 1 diabetes, 24 type 2 diabetic patients either insulin-free or
      undergoing insulin treatment for at least six months, and 15 healthy subjects.
      Specific dimensions of fatigue were assessed using the Multidimensional-Fatigue
      Inventory (MFI). Cognitive performance on tests of choice reaction time, pattern
      recognition memory and spatial planning was evaluated using the Cambridge
      Neuropsychological-Automated-Battery (CANTAB). Body mass index (BMI) and glycated
      hemoglobin (HbA1C) concentrations were collected, as well as information on
      diabetes complications and disease duration. Patients with type 2 diabetes,
      regardless of insulin treatment status, exhibited higher scores of fatigue,
      primarily in the dimensions of general and physical fatigue as well as reduced
      activity. Cognitive alterations, in the form of longer reaction times and
      impaired spatial planning, were also detected in type 2 diabetic patients treated
      with insulin. These alterations were overall unrelated to glucose control, as
      reflected in HbA1C levels, and were not explained by complications and duration
      of diabetes. No specific alteration was measured in type 1 diabetic patients who
      exhibited fatigue scores and cognitive performance comparable to healthy
      participants. While associated with fatigue, increased BMI did not significantly
      account for the relationship of type 2 diabetes with general fatigue and physical
      fatigue. BMI, however, modulated the association of type 2 diabetes with reduced
      activity and the association of insulin-treated type 2 diabetes with psychomotor
      slowing. These findings reveal specific fatigue and cognitive symptoms in
      patients with type 2 diabetes and suggest the involvement of differential
      pathophysiological processes.

PMID- 22370461
TI  - Comparison of ankle-brachial index in patients with and without atrial
      fibrillation.
AB  - The aim of this study was to compare the ankle-brachial index between patients
      with atrial fibrillation (AF) and those without atrial fibrillation. MATERIAL AND
      METHODS: A total of 286 patients admitted to the Departments of Neurology or
      Cardiology, Kaunas Clinical Hospital, during 2008-2010 and referred for a
      consultation with an internist and/or a cardiologist were included in this study.
      All patients had at least one prevalent cardiovascular disorder and were screened
      for diagnosis of permanent AF based on medical records and electrocardiogram and
      evaluated for the ankle-brachial index (ABI). Peripheral artery disease (PAD) was
      defined as an ABI of <0.9 assessed by using a 5-MHz Doppler ultrasound device.
      RESULTS: The patients with permanent AF had a significantly lower ABI compared
      with the patients without AF (P<0.001). Binary regression analysis revealed that
      permanent AF was associated with PAD (OR, 2.5; 95% 1.5-4.2). The likelihood of
      having an ABI of <0.9 increased with each additional risk factor: AF (OR, 2.2;
      95% CI, 1.3-3.8), stroke (OR, 2.3; 95% CI, 1.3-4.2), age of >69 years (OR, 2.4;
      95% CI, 1.3-4.7), and myocardial infarction (OR, 2.4; 95% CI, 1.1-5.5). Nearly
      one-fourth (24.5%) of all patients with an ABI of <0.9 did not report any PAD
      specific symptoms. CONCLUSIONS: The patients with cardiovascular disorders and
      permanent atrial fibrillation were found to have a significantly lower mean ankle
      brachial index and higher prevalence of peripheral artery disease compared with
      cardiovascular patients without atrial fibrillation. The patients who were found
      to have a lower ankle-brachial index and permanent atrial fibrillation were older
      and often had several cardiovascular diseases (angina pectoris, stroke,
      myocardial infarction, or hypertension).

PMID- 22370462
TI  - Microflora of the oral cavity in patients with xerostomia.
AB  - OBJECTIVE: The aim of this study was to evaluate the dependence of the condition
      of the microflora of the oral cavity on the etiology of xerostomia, patients'
      sex, age, degree of hyposalivation, and duration of the sense of dryness.
      MATERIAL AND METHODS: A total of 64 patients with complaints of oral dryness
      referred to the Clinic of Oral and Dental Diseases, Hospital of Lithuanian
      University of Health Sciences, for consultation during the period from 2003 to
      2005 were selected for the study. The etiological factors of xerostomia were as
      follows: radiotherapy (PRT) to the maxillofacial area, Sjogren's syndrome (SS),
      and xerogenic medications, tricyclic antidepressants (TCAs). RESULTS: There were
      50 women and 14 men. Their mean age was 60.5 +/- 1.6 years. All the patients in
      the PRT group had high counts of Candida spp. as compared with percentages of
      patients in the TCA and SS groups (100% vs. 66.7% and 56.2%, P<0.05). Patients'
      age and sex in different etiology groups had no significant impact on the
      condition of their oral microflora. There were equal percentages of patients with
      deficient and normal salivation in the TCA group (44% in both the groups;
      P<0.01). All the patients in the PRT group had pronounced hyposalivation
      (P<0.002). A significantly greater percentage of patients with severely reduced
      salivation had high counts of Lactobacillus spp. (P<0.01). Significantly greater
      percentages of patients with the clinical duration of xerostomia of up to 6
      months had high counts of Lactobacillus spp. and Candida spp. colonies.
      CONCLUSIONS: In patients with xerostomia, the condition of the microflora of the
      oral cavity and impairment of major salivary gland function varied according to
      the etiology of the disease. The level of hyposalivation and the duration of
      xerostomia were found to have a significant impact on the microflora of the oral
      cavity.

PMID- 22370463
TI  - Characteristics of carbapenem-resistant Pseudomonas aeruginosa strains in
      patients with ventilator-associated pneumonia in intensive care units.
AB  - The aim of this study was to determine the characteristics of carbapenem
      resistant Pseudomonas aeruginosa (P. aeruginosa) strains and 5-year changes in
      resistance in a tertiary university hospital. MATERIAL AND METHODS: The study
      included 90 and 101 randomly selected P. aeruginosa strains serotyped in 2003 and
      2008, respectively. The standardized disk diffusion test and E-test were used to
      determine resistance to antibiotics. P. aeruginosa strains were considered to
      have high-level resistance if a minimum inhibitory concentration (MIC) for
      imipenem or meropenem was >32 ug/mL. To identify serogroups, sera containing
      specific antibodies against O group antigens of P. aeruginosa were used. P.
      aeruginosa isolates resistant to imipenem or/and meropenem were screened for
      metallo-beta-lactamase (MBL) production by using the MBL E-test. RESULTS:
      Comparison of the changes in resistance of P. aeruginosa strains to carbapenems
      within the 5-year period revealed that the level of resistance to imipenem
      increased. In 2003, 53.3% of P. aeruginosa strains were found to be highly
      resistant to imipenem, while in 2008, this percentage increased to 87.8%
      (P=0.01). The prevalence of MBL-producing strains increased from 15.8% in 2003 to
      61.9% in 2008 (P<0.001). In 2003 and 2008, carbapenem-resistant P. aeruginosa
      strains were more often resistant to ciprofloxacin and gentamicin than carbapenem
      sensitive strains. In 2008, carbapenem-resistant strains additionally were more
      often resistant to ceftazidime, cefepime, aztreonam, piperacillin, and amikacin
      than carbapenem-sensitive strains. MBL-producing P. aeruginosa strains belonged
      more often to the O:11 serogroup than MBL-non-producing strains (51.7% vs. 34.3%,
      P<0.05). A greater percentage of non-MBL-producing strains had low MICs against
      ciprofloxacin and amikacin as compared with MBL-producing strains. CONCLUSIONS:
      The results of our study emphasize the need to restrict the spread of O:11
      serogroup P. aeruginosa strains and usage of carbapenems to treat infections with
      P. aeruginosa in the intensive care units of our hospital.

PMID- 22370464
TI  - The relationship between seropositivity against Chlamydia pneumoniae and stroke
      and its subtypes in a Latvian population.
AB  - BACKGROUND AND OBJECTIVE: Serological evidence of infection with Chlamydia
      pneumoniae has been associated with cardiovascular diseases, but the relationship
      with stroke and its risk factors remains not completely understood. The aim of
      this study was to determine whether serological evidence of infection with
      Chlamydia pneumoniae was associated with the risk of ischemic stroke and any of
      investigated stroke subtypes. MATERIAL AND METHODS: Confirmed stroke cases
      (n=102) were compared with gender- and age-matched control patients (n=48). The
      patients with stroke were divided into 3 groups according to the TOAST criteria:
      atherothrombotic (n=36), cardioembolic (n=47), and of undetermined etiology
      (n=19). Plasma levels of IgG antibodies to Chlamydia pneumoniae were measured by
      enzyme-linked immunosorbent assay. RESULTS: There was a significant association
      between seropositivity to Chlamydia pneumoniae and stroke. Anti-Chlamydia
      pneumoniae IgG antibodies were detected in 64 case patients (62.7%) and 17
      control patients (35.4%) (chi(2)=9.8; df=1; P=0.002). IgG seropositivity to
      Chlamydia pneumoniae was linked to all the analyzed etiological subtypes of
      stroke. CONCLUSION: This study showed that IgG seropositivity to Chlamydia
      pneumoniae was associated with stroke and all the analyzed etiological subtypes
      of stroke.

PMID- 22370465
TI  - Regional differences in diagnosing asthma and other allergic diseases in Estonian
      schoolchildren.
AB  - The aim of this study was to estimate the prevalence of asthma and other allergic
      diseases among Estonian schoolchildren of the cities lacking special (pediatric
      allergological) health care. MATERIAL AND METHODS: The study, carried out through
      1 March to 8 May, 2003, enrolled 5th- to 12th-grade schoolchildren of 4 schools
      in different regions of Estonia. A three-step protocol was followed: screening
      questionnaire, examination by a pulmonary resident, and consultation by a
      pediatric allergologist. RESULTS: Of the 3132 questionnaires distributed, 1561
      (49%) were returned. A total of 828 schoolchildren answered positively to any of
      the questions about possible allergic disease. After examination by the pulmonary
      resident, 255 schoolchildren (15.7%) were referred to an allergologist for final
      diagnosis. Asthma was diagnosed in 4.8%, allergic rhinoconjunctivitis in 4.9%,
      and atopic eczema in 8.3% of schoolchildren. Asthma, allergic
      rhinoconjunctivitis, and urticaria occurred more frequently in Narva as compared
      with Voru. CONCLUSION: The 12-month prevalence of asthma among Estonian
      schoolchildren was 4.8%, and the prevalence of allergic diseases varied from
      region to region. Less than half (40%) of all asthma cases identified during the
      study were newly diagnosed, and this clearly indicates that there is a
      considerable underdiagnosis of the disease among schoolchildren living outside of
      the centers in Estonia.

PMID- 22370466
TI  - Mortality of children under five and prevalence of newborn congenital anomalies
      in relation to macroeconomic and socioeconomic factors in Latvia.
AB  - BACKGROUND: Mortality of infants and children younger than 5 years is a globally
      recognized and broad national welfare indicator. Scientific literature has data
      on the correlation of mortality indicators with macroeconomic indicators. It is
      important to study the associations between prevalence and mortality indicators
      and socioeconomic factors, since deaths from congenital anomalies account for
      approximately 25%-30% of all deaths in infancy. The aim of the study was to
      analyze the overall trend in mortality of infants and young children aged 0 to 4
      years in relation to macroeconomic factors in Latvia and prevalence of congenital
      anomalies in newborns in relation to socioeconomic factors. MATERIAL AND METHODS:
      The Newborns' Register and Causes of Death Register were used as data sources;
      data on specific socioeconomic factors were retrieved from the Central Statistics
      Office. RESULTS: The results of the study show a strong correlation between
      mortality in children younger than 5 years and gross domestic product, as well as
      health budget in LVL per capita and the national unemployment level. The average
      decrease in infant mortality from congenital anomalies in Latvia was found to be
      6.8 cases per 100,000 live births. CONCLUSIONS: There is a strong correlation
      between child mortality and socioeconomic situation in the country. There is a
      need to analyze the data on child mortality in a transnational context on a
      regular basis and studying the correlations between child mortality indicators
      and socioeconomic indicators and health care management parameters.

PMID- 22370467
TI  - Factors influencing psychoemotional strain and fatigue, and relationship of these
      factors with health complaints at sea among Lithuanian seafarers.
AB  - The aim of the study was to identify the factors influencing psychoemotional
      strain and, fatigue among Lithuanian seafarers and relationship of these factors
      to health complaints at sea. MATERIAL AND METHODS: Two questionnaire surveys were
      carried out during mandatory health examination at the Maritime Medicine Center
      of Klaipeda Seamen's Hospital in 2003 and 2007. From November to December 2003,
      998 seafarers aged 20-64 years were interviewed (first study). The second study
      carried out during November-December 2007 involved 932 20-64-year-old seafarers.
      The questionnaire comprised questions on sociodemographic data, factors of
      maritime industry, experienced psychoemotional strain and fatigue, and subjective
      evaluation of health. RESULTS: The first study showed that older seafarers aged
      from 35 to 54 years were more likely to experience psychoemotional strain
      (P<0.001). Long working hours (9-10 hours and 11-12 hours) in harmful conditions
      and increased eyestrain were associated with psychoemotional strain among
      seafarers in the first study as well (P<0.001). Higher education level and
      detrimental factors to health (vibration and noise) were significant risk factors
      for the occurrence of psychoemotional strain among seafarers in the second study
      (P<0.05). The relationship between many risk factors related to seafarers' work,
      demographic data, and subjectively evaluated psychoemotional strain and fatigue
      appear to be accumulative in character. Health complains at sea (insomnia,
      depression, waist and spinal pain) were related to psychoemotional strain, but
      sleep disorders were associated with fatigue. CONCLUSIONS: Seafarers employed on
      a certain ship, under particular conditions, and being exposed to risk factors or
      their combination may experience health disorders related to increased fatigue
      and psychoemotional strain.

PMID- 22370468
TI  - Cloacal exstrophy: a case report and literature review.
AB  - Cloacal exstrophy is an extremely rare congenital malformation resulting in an
      exstrophy of the urinary, intestinal, and genital organs and associated with
      anomalies of other organ systems. We present a complicated case of cloacal
      exstrophy and the recent progress in the management of this probably most
      complicated anomaly in pediatric urology and surgery.

PMID- 22370470
TI  - Long-term effect of phacoemulsification on intraocular pressure using phakic
      fellow eye as control.
AB  - PURPOSE: To investigate the long-term effect of phacoemulsification on
      intraocular pressure (IOP) in patients with ocular hypertension and open-angle
      glaucoma. SETTING: Three multispecialty ophthalmology practices and one glaucoma
      specialty group. DESIGN: Retrospective comparative case series. METHODS: Review
      of medical records of patients with open-angle glaucoma or ocular hypertension
      who had had unilateral phacoemulsification (without other prior or concurrent
      ophthalmic procedure) with the fellow eye remaining phakic at least 3 years
      postoperatively. RESULTS: Preoperatively, the IOP in the surgical and fellow eyes
      in the 29 patients was 15.66 mm Hg +/- 3.33 (SD) and 15.64 +/- 4.23 mm Hg
      (P=.98), respectively. Postoperatively, it was 13.56 +/- 2.04 mm Hg and 14.92 +/-
      2.85 mm Hg, respectively, at 4.5 months (P=.06); 14.88 +/- 3.20 mm Hg and 15.27
      +/- 3.19 mm Hg, respectively, at 1 year (P=.67); 14.16 +/- 2.61 mm Hg and 14.95
      +/- 2.79 mm Hg, respectively, at 2 years (P=.37); and 14.68 +/- 3.44 mm Hg and
      14.68 +/- 2.68 mm Hg at 3 years (P=1.00), respectively. There was no significant
      difference in the mean number of IOP-lowering medications used in the surgical
      eyes (1.96 +/- 1.40) and fellow eyes (2.08 +/- 1.44) postoperatively (P=.77).
      CONCLUSIONS: In a cohort of ocular hypertensive and glaucoma patients,
      uncomplicated phacoemulsification had no significant IOP-lowering effect compared
      with the phakic fellow eye for up to 3 years postoperatively. There was also no
      difference between the mean number of postoperative IOP-lowering medications used
      in the surgical and fellow eyes. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 22370471
TI  - Theoretical investigation of structural and electronic propertyies of [PW12O40]3-
      on graphene layer.
AB  - The structural and electronic properties of [PW(12)O(40)](3-) (PW(12)) anion
      deposited on a graphene layer are investigated by using periodic density
      functional theory. The equilibrium geometries of graphene-PW(12) (G-PW(12)) are
      examined based on six different configurations. The adsorption energy and charge
      transfer between PW(12) and graphene are calculated and analyzed. We found that
      the interaction between PW(12) and graphene are noncovalent. The formation of G
      PW(12) complex is theoretically predicted to be feasible from an energetic
      perspective with electron transfer from the PW(12) to graphene.

PMID- 22370472
TI  - Przewalskone: a cytotoxic adduct of a danshenol type terpenoid and an icetexane
      diterpenoid via hetero-Diels-Alder reaction from Salvia przewalskii.
AB  - Przewalskone (1), an unprecedented adduct of two different terpenoid units via a
      hetero-Diels-Alder cycloaddition, was isolated from the roots of Salvia
      przewalskii. The structure and absolute configurations were elucidated by
      extensive analysis of NMR spectra and crystal X-ray diffractions. Compound 1
      exhibited significant cytotoxicities against five human cancer lines in vitro
      (IC(50) 0.69-2.35 MUM).

PMID- 22370474
TI  - Structural evaluation of probucol nanoparticles in water by atomic force
      microscopy.
AB  - Structural evaluation of probucol nanoparticles coground with
      polyvinylpyrrolidone K17 and sodium dodecyl sulfate for 90 min was performed by
      solid-state nuclear magnetic resonance (NMR) spectroscopy and atomic force
      microscopy (AFM) with force-distance curve analysis. The results of solid-state
      NMR indicated that the cogrinding changed crystalline probucol to amorphous form.
      The number-averaged mean heights of probucol particles in the ground mixture (GM)
      suspension were determined by AFM to be 6 and 15 nm for freshly prepared and 24h
      stored samples, respectively. Nucleation and the subsequent crystal growth might
      have occurred after the GM was dispersed in water. The presence of probucol
      nanocrystals and agglomeration of the primary probucol nanoparticles were
      recognized by AFM force-distance curve analysis. AFM could be a promising tool to
      evaluate the structure of nanoparticles as well as their agglomeration behavior
      in aqueous media.

PMID- 22370475
TI  - Relationship between dissolution and bioavailability for nimodipine colloidal
      dispersions: the critical size in improving bioavailability.
AB  - To compare the dissolution and bioavailability for nimodipine microcrystals and
      nanocrystals, and to determine the critical size range in improving the oral
      absorption of nimodipine. Nimodipine microcrystals and nanocrystals were prepared
      using a microprecipitation method. The particle size was determined with a laser
      diffraction method. X-ray powder diffraction was applied to inspect the potential
      crystal form transition. The aqueous solubility was determined by shaking flasks,
      and the dissolution behavior was evaluated using the paddle method. The
      pharmacokinetics was performed in beagle dogs in a crossover experimental design.
      Three nimodipine colloidal dispersions (16296.7, 4060.0 and 833.3 nm) were
      prepared, respectively. Nimodipine had undergone crystal form transition during
      microprecipitation process, but experienced no conversion under the high-pressure
      homogenization. The colloidal dispersions did not show any difference in aqueous
      equilibrium solubility. Additionally, the three formulations also displayed
      similar dissolution curves in purified water and 0.05% SDS. The AUC for
      dispersions of 4060.0 and 833.3 nm sizes was 1.69 and 2.59-fold higher than that
      for 16296.7 nm system in dogs. To sum up, the critical particle size was found to
      be within the range of 833.3-4060.0 nm (average volume-weighted particle size) in
      improving the bioavailability of nimodipine, and dissolution performance was not
      an effective index in evaluating the bioavailability for nimodipine colloidal
      dispersions.

PMID- 22370476
TI  - Quality changes of sea bass slices wrapped with gelatin film incorporated with
      lemongrass essential oil.
AB  - Microbiological, chemical and physical changes of sea bass slices wrapped with
      gelatin film incorporated with 25% (w/w) lemongrass essential oil (LEO) during
      storage of 12 days at 4  degrees C were investigated. Sea bass slices wrapped
      with LEO film had the retarded growth of lactic acid bacteria (LAB),
      psychrophilic bacteria and spoilage microorganisms including H2S-producing
      bacteria and Enterobacteriaceae throughout storage of 12 days in comparison with
      the control and those wrapped with gelatin film without LEO (G film) (P<0.05).
      Lowered changes of colour, K value, total volatile base nitrogen (TVB) and TBARS
      value were also found in LEO film wrapped samples, compared with those wrapped
      with G film and control, respectively. Therefore, the incorporation of LEO into
      gelatin film could enhance the antimicrobial and antioxidative properties of the
      film, thereby maintaining the qualities and extending the shelf-life of the sea
      bass slices stored at refrigerated temperature.

PMID- 22370477
TI  - Autophagy attenuates the adaptive immune response by destabilizing the
      immunologic synapse.
AB  - BACKGROUND & AIMS: Variants in the genes ATG16L1 and IRGM affect autophagy and
      are associated with the development of Crohn's disease. It is not clear how
      autophagy is linked to loss of immune tolerance in the intestine. We investigated
      the involvement of the immunologic synapse-the site of contact between dendritic
      cells (DCs) and T cells, which contains molecules involved in antigen recognition
      and regulates immune response. METHODS: DC autophagy was reduced using small
      interfering RNAs or pharmacologic inhibitors. DC phenotype and function were
      analyzed by confocal microscopy, time-lapse microscopy, and flow cytometry. We
      also examined DCs isolated from patients with Crohn's disease who carried the
      ATG16L1 risk allele. RESULTS: Immunologic synapse formation induced formation of
      autophagosomes in DCs; the autophagosomes were oriented toward the immunologic
      synapse and contained synaptic components. Knockdown of ATG16L1 and IRGM with
      small interfering RNAs in DCs resulted in hyperstable interactions between DCs
      and T cells, increased activation of T cells, and activation of a T-helper 17
      cell response. LKB1 was recruited to the immunologic synapse, and induction of
      autophagy in DC required inhibition of mammalian target of rapamycine signaling
      by the LKB1-AMP activated protein kinase (AMPK) pathway. DCs from patients with
      Crohn's disease who had an ATG16L1 risk allele had a similar hyperstability of
      the immunologic synapse. CONCLUSIONS: Autophagy is induced upon formation of the
      immunologic synapse and negatively regulates T-cell activation. This mechanism
      might increase adaptive immunity in patients with Crohn's disease who carry
      ATG16L1 risk alleles.

PMID- 22370478
TI  - Defects in gallbladder emptying and bile Acid homeostasis in mice with cystic
      fibrosis transmembrane conductance regulator deficiencies.
AB  - BACKGROUND & AIMS: Patients with cystic fibrosis (CF) have poorly defined defects
      in biliary function. We evaluated the effects of cystic fibrosis transmembrane
      conductance regulator (CFTR) deficiency on the enterohepatic disposition of bile
      acids (BAs). METHODS: Bile secretion and BA homeostasis were investigated in
      Cftr(tm1Unc) (Cftr-/-) and CftrDeltaF508 (DeltaF508) mice. RESULTS: Cftr-/- and
      DeltaF508 mice did not grow to normal size, but did not have liver abnormalities.
      The gallbladders of Cftr-/- mice were enlarged and had defects in emptying, based
      on (99m)technetium-mebrofenin scintigraphy or post-prandial variations in
      gallbladder volume; gallbladder contraction in response to cholecystokinin-8 was
      normal. Cftr-/- mice had abnormal gallbladder bile and duodenal acidity, and
      overexpressed the vasoactive intestinal peptide-a myorelaxant factor for the
      gallbladder. The BA pool was larger in Cftr-/- than wild-type mice, although
      there were no differences in fecal loss of BAs. Amounts of secondary BAs in
      portal blood, liver, and bile of Cftr-/- mice were much lower than normal.
      Expression of genes that are induced by BAs, including fibroblast growth factor
      15 and BA transporters, was lower in the ileum but higher in the gallbladders of
      Cftr-/- mice, compared with wild-type mice, whereas enzymes that synthesize BA
      were down-regulated in livers of Cftr-/- mice. This indicates that BAs underwent
      a cholecystohepatic shunt, which was confirmed using cholyl-(Ne-NBD)-lysine as a
      tracer. In Cftr-/- mice, cholecystectomy reversed most changes in gene expression
      and partially restored circulating levels of secondary BAs. The DeltaF508 mice
      overexpressed vasoactive intestinal peptide and had defects in gallbladder
      emptying and in levels of secondary BAs, but these features were less severe than
      in Cftr-/- mice. CONCLUSIONS: Cftr-/- and CftrDeltaF508 mice have defects in
      gallbladder emptying that disrupt enterohepatic circulation of BAs. These defects
      create a shunt pathway that restricts the amount of toxic secondary BAs that
      enter the liver.

PMID- 22370479
TI  - Vitamin D has wide regulatory effects on histone demethylase genes.
AB  - Vitamin D from the diet or synthesized in the skin upon UV-B irradiation is
      converted in the organism into the active metabolite 1alpha,25- dihydroxyvitamin
      D 3 [1,25(OH) 2D 3, calcitriol], a pleiotropic hormone with wide regulatory
      actions. The classical model of 1,25(OH)2D3 action implies the activation of the
      vitamin D receptor, which binds specific DNA sequences in its target genes and
      modulates their transcription rate. We have recently shown that 1,25(OH) 2D 3
      induces the expression of the JMJD3 gene coding for a histone demethylase that is
      involved in epigenetic regulation. JMJD3 mediates the effects of 1,25(OH) 2D 3 on
      a subset of target genes and affects the expression of ZEB1, ZEB2 and SNAI1,
      inducers of epithelial-mesenchymal transition. Novel data indicate that 1,25(OH)
      2D 3 has an unanticipated wide regulatory action on the expression of genes
      coding for histone demethylases of the Jumonji C (JmjC) domain and lysine
      specific demethylase (LSD) families. Moreover, JMJD3 knockdown decreases the
      expression of miR-200b and miR-200c, two microRNAs targeting ZEB1 RNA. This may
      explain the upregulation of this transcription factor found in JMJD3-depleted
      cells. Thus, 1,25(OH) 2D 3 exerts an ample regulatory effect on the expression of
      histone-modifying enzymes involved in epigenetic regulation that may mediate its
      actions on gene transcription and cell phenotype.

PMID- 22370480
TI  - Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent
      prostate cancer cells to TRAIL.
AB  - We previously reported that the NO-modified form of HIV protease inhibitor
      Saquinavir (Saq) is a potent antitumoral agent efficient against numerous tumor
      cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO
      equivalent to DL100 of the parental drug were completely nontoxic. Beside direct
      effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. In
      this study, we evaluated the effects of Saq-NO on androgen-dependent prostate
      cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in
      xenograft models. Suppression of tumor growth was accompanied with cell cycle
      arrest in G 0/G 1 phase and established a persistent inhibition of proliferation.
      Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF.
      Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2.
      This, however, did not represent the primary mode of action of Saq-NO, as
      elimination with specific inhibitors did not compromise the chemotherapic
      efficacy of the drug. However, permanent abrogation of phosphorylation of the S6
      protein, which is the downstream target of both signaling pathways, was observed.
      Diminished S6 phosphorylation was associated with re-established sensitivity to
      TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In
      summary, NO modification of Saq led to a new chemical entity with stronger and
      more pleiotropic antitumor activity than the parental drug.

PMID- 22370481
TI  - Regulation of oxidative DNA damage repair: the adenine:8-oxo-guanine problem.
AB  - Reactive oxygen species (ROS) constantly attack DNA. One of the best
      characterized oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxo-G). Many
      human diseases, such as cancer and neurodegenerative disorders, have been
      correlated with oxidative DNA damage. In the last few years, DNA polymerase (Pol)
      lambda, one of the 15 cellular Pols, has been identified to play an important
      role in performing accurate translesion synthesis over 8-oxo-G. This is eminently
      important, since normally faithful replicative Pols alpha, delta and epsilon,
      with their tight active center, often wrongly incorporate adenine (A) opposite
      the 8-oxo-G lesion. A:8- oxo-G mispairs are accurately repaired by the pathway
      identified in our laboratory involving MutY DNA glycosylase homolog (MutYH) and
      Pol lambda. Until now, very little was known about the spatial and temporal
      regulation of Pol lambda and MutYH in active repair complexes. We now showed in
      our latest publication that the E3 ligase Mule can ubiquitinate and degrade Pol
      lambda, and that the control of Pol lambda levels by Mule has functional
      consequences for the ability of mammalian cells to deal with 8-oxo-G lesions. In
      contrast, phosphorylation of Pol lambda by Cdk2/cyclinA counteracts this
      degradation by recruiting it to MutYH on chromatin to form active 8-oxo-G repair
      complexes.

PMID- 22370482
TI  - The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation under diverse stress
      conditions.
AB  - Modification of proteins with ubiquitin and ubiquitin-like molecules is involved
      in the regulation of almost every biological process. Historically, each
      conjugation pathway has its unique set of E1, E2 and E3 enzymes that lead to
      activation and conjugation of their cognate molecules. Here, we present the
      unexpected finding that under stress conditions, the ubiquitin E1 enzyme Ube1
      mediates conjugation of the ubiquitin-like molecule NEDD8. Inhibition of the 26S
      proteasome, heat shock and oxidative stress cause a global increase in
      NEDDylation. Surprisingly, this does not depend on the NEDD8 E1-activating
      enzyme, but rather on Ube1. A common event in the tested stress conditions is the
      depletion of "free" ubiquitin. A decrease in "free" ubiquitin levels in the
      absence of additional stress is sufficient to stimulate NEDDylation through Ube1.
      Further analysis on the NEDD8 proteome shows that the modified NEDDylated
      proteins are simultaneously ubiquitinated. Mass spectrometry on the complex
      proteome under stress reveals the existence of mixed chains between NEDD8 and
      ubiquitin. We further show that NEDDylation of the p53 tumor suppressor upon
      stress is mediated mainly through Ube1. Our studies reveal an unprecedented
      interplay between NEDD8 and ubiquitin pathways operating in diverse cellular
      stress conditions.

PMID- 22370484
TI  - SENP1 deficiency promotes ER stress-induced apoptosis by increasing XBP1
      SUMOylation.
AB  - The transcription factor X box-binding protein 1 (XBP1) is a key component of the
      endoplasmic reticulum (ER) stress response. Recently, it has been reported that
      the spliced XBP1 (XBP1s), an activated XBP1 during ER stress, can be SUMOylated.
      Here, we identify Sentrin/SUMO-specific protease 1 (SENP1) as a specific de
      SUMOylation protease for XBP1. SENP1 can increase the transcriptional activity of
      XBP1. In Senp1 (-/-)  cells, the SUMOylated XBP1 is accumulated, and the
      expression of XBP1 target genes is downregulated in response to ER stress.
      Moreover, SENP1 deficiency significantly increases ER stress-induced apoptosis
      through accumulating XBP1 SUMOylation. These results reveal an essential function
      of SENP1 in ER stress response through regulating XBP1 SUMOylation.

PMID- 22370483
TI  - The ubiquitin-specific protease USP2a enhances tumor progression by targeting
      cyclin A1 in bladder cancer.
AB  - The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer
      types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant
      expression of USP2a has been linked to progression of human tumors, particularly
      prostate cancer. However, little is known about the role of USP2a or its
      mechanism of action in bladder cancer. Here, we provide evidence that USP2a is an
      oncoprotein in bladder cancer cells. Enforced expression of USP2a caused enhanced
      proliferation, invasion, migration and resistance to several chemotherapeutic
      reagents, while USP2a loss resulted in slower proliferation, greater
      chemosensitivity and reduced migratory/invasive capability compared with control
      cells. USP2a, but not a catalytically inactive mutant, enhanced proliferation in
      immortalized TRT-HU1 normal human bladder epithelial cells. USP2a bound to cyclin
      A1 and prevented cyclin A1 ubiquitination, leading to accumulation of cyclin A1
      by a block in degradation. Enforced expression of wild type USP2a, but not an
      inactive USP2a mutant, resulted in cyclin A1 accumulation and increased cell
      proliferation. We conclude that USP2a impairs ubiquitination and stabilizes an
      important cell cycle regulator, cyclin A1, raising the possibility of USP2a
      targeting as a therapeutic strategy against bladder tumors in combination with
      chemotherapy.

PMID- 22370485
TI  - Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme
      radiosensitization and growth control.
AB  - Glioblastoma multiforme (GBM) is notoriously resistant to treatment. Therefore,
      new treatment strategies are urgently needed. ATM elicits the DNA damage response
      (DDR), which confers cellular radioresistance; thus, targeting the DDR with an
      ATM inhibitior (ATMi) is very attractive. Herein, we show that dynamic ATM kinase
      inhibition in the nanomolar range results in potent radiosensitization of human
      glioma cells, inhibits growth and does not conflict with temozolomide (TMZ)
      treatment. The second generation ATMi analog KU-60019 provided quick, reversible
      and complete inhibition of the DDR at sub-micromolar concentrations in human
      glioblastoma cells. KU-60019 inhibited the phosphorylation of the major DNA
      damage effectors p53, H2AX and KAP1 as well as AKT. Colony-forming radiosurvival
      showed that continuous exposure to nanomolar concentrations of KU-60019
      effectively radiosensitized glioblastoma cell lines. When cells were co-treated
      with KU-60019 and TMZ, a slight increase in radiation-induced cell killing was
      noted, although TMZ alone was unable to radiosensitize these cells. In addition,
      without radiation, KU-60019 with or without TMZ reduced glioma cell growth but
      had no significant effect on the survival of human embryonic stem cell (hESC)
      derived astrocytes. Altogether, transient inhibition of the ATM kinase provides a
      promising strategy for radiosensitizing GBM in combination with standard
      treatment. In addition, without radiation, KU-60019 limits growth of glioma cells
      in co-culture with human astrocytes that seem unaffected by the same treatment.
      Thus, inter-fraction growth inhibition could perhaps be achieved in vivo with
      minor adverse effects to the brain.

PMID- 22370486
TI  - Taper-free and kinked germanium nanowires grown on silicon via purging and the
      two-temperature process.
AB  - We investigate the growth procedures for achieving taper-free and kinked
      germanium nanowires epitaxially grown on silicon substrates by chemical vapor
      deposition. Singly and multiply kinked germanium nanowires consisting of <111>
      segments were formed by employing a reactant gas purging process. Unlike non
      epitaxial kinked nanowires, a two-temperature process is necessary to maintain
      the taper-free nature of segments in our kinked germanium nanowires on silicon.
      As an application, nanobridges formed between (111) side walls of V-grooved (100)
      silicon substrates have been demonstrated.

PMID- 22370488
TI  - Depression in cultural context: "Chinese somatization," revisited.
AB  - We have presented a view of culture and mental health that builds on work in
      cultural psychiatry, anthropology, and cultural psychology, and applied it to
      research on culture and depression. In particular, we have returned to the well
      known topic of Chinese somatization. A culture-mind-brain approach to these
      questions helps us think about them in a way that points toward new research. We
      have applied this approach to thinking about a single set of questions, relevant
      to a single (DSM-based) diagnosis, in a single cultural group. The potential,
      however, is to rethink how we conceptualize mental health in ways consistent with
      cultural psychiatry's general perspective over the past several decades, while
      incorporating rather than rejecting the many recent advances in brain and
      behavior sciences. In so doing, we gain a more expanded and nuanced view of the
      global landscape of mental health, accompanied by a more expanded and nuanced
      view of individual patients.

PMID- 22370489
TI  - Recovery from depression.
AB  - Full recovery from depression, as contrasted with symptom improvement, is a
      relatively new concept and therapeutic goal. It is an important goal, because the
      failure to achieve this goal leaves many patients with less productive and
      fulfilling lives, it leaves some children with lasting deficits, and it deprives
      families and societies of loved ones' and employees' care and investment. As a
      new therapeutic concept, recovery from depression is not as easy to define as it
      might seem; many or most patients were not euthymic before an episode of
      depression or have had some level of depression throughout their lives. There is
      no measurable definition of euthymia. In addition to definitional difficulties,
      we need to study and address other barriers to the achievement of recovery from
      depression. All the barriers to the diagnosis and treatment of depression are
      barriers against recovery: negative social and professional attitudes,
      comorbidity, lack of access to demonstrably efficacious professional and social
      services, and inability to match patients with the antidepressants most likely to
      help them. Efforts to address many of these knowledge and attitude gaps are
      already underway. Long-term studies are needed, both observational and
      experimental. Most published studies encompass only weeks or at best months of
      follow-up, but recovery must be sustained to be meaningful. As noted previously,
      there has been little or no attention to the developmental impact of depression.
      The restoration of premorbid function is not sufficient when depression has
      hindered a patient's ability to form satisfying relationships and choose and
      perform satisfying work. We need to learn how to remediate patients whose history
      of depression has stifled their talents and aspirations. Studying these issues
      will not be easy, but millions of individuals with depression, and their
      physicians, will profit by it; it will be well worth the effort.

PMID- 22370487
TI  - The costs of depression.
AB  - The data reported herein show clearly that major depression is a commonly
      occurring and burdensome disorder. The high prevalence, early age of onset, and
      high persistence of MDD in the many different countries where epidemiologic
      surveys have been administered confirm the high worldwide importance of
      depression. Although evidence is not definitive that MDD plays a causal role in
      its associations with the many adverse outcomes reviewed here, there is clear
      evidence that depression has causal effects on a number of important mediators,
      making it difficult to assume anything other than that depression has strong
      causal effects on many dimensions of burden. These results have been used to
      argue for the likely cost -effectiveness of expanded depression treatment from a
      societal perspective. Two separate, large-scale, randomized, workplace depression
      treatment effectiveness trials have been carried out in the United States to
      evaluate the cost effectiveness of expanded treatment from an employer
      perspective. Both trials had positive returns on investment to employers. A
      substantial expansion of worksite depression care management programs has
      occurred in the United States subsequent to the publication of these trials.
      However, the proportion of people with depression who receive treatment remains
      low in the United States and even lower in other parts of the world. A recent US
      study found that only about half of workers with MDD received treatment in the
      year of interview and that fewer than half of treated workers received treatment
      consistent with published treatment guidelines. Although the treatment rate was
      higher for more severe cases, even some with severe MDD often failed to receive
      treatment. The WMH surveys show that treatment rates are even lower in many other
      developed countries and consistently much lower in developing countries. Less
      information is available on rates of depression treatment among patients with
      chronic physical disorders, but available evidence suggests that expanded
      treatment could be of considerable value. Randomized, controlled trials are
      needed to expand our understanding of the effects of detection and treatment of
      depression among people in treatment for chronic physical disorders. In addition,
      controlled effectiveness trials with long-term follow-ups are needed to increase
      our understanding of the effects of early MDD treatment interventions on changes
      in life course role trajectories, role performance, and onset of secondary
      physical disorders.

PMID- 22370490
TI  - Etiology of depression: genetic and environmental factors.
AB  - In summary, depressed patients with a history of childhood trauma may have a
      distinct depression endophenotype characterized by a specific neurobiology and
      risk genotype that may be responsive to different treatment strategies than
      depressed patients without childhood adversity. Based on current findings,
      treatment strategies should be multimodal and include the following: 1.
      Psychotherapy that addresses a number of domains, such as emotional regulation,
      cognitive reframing, careful exploration of past traumatic events, attachment,
      and interpersonal relationships in a safe and trusting therapeutic environment.
      2. The therapy should likely be longer term in order to effectively impact those
      domains. 3. Pharmacotherapy that will be effective in quieting the body's
      hyperresponsiveness to stress and reverse epigenetic modifications induced by
      trauma and stress. 4. Environmental interventions that provide a support network
      (maternal care, a positive family environment, the support of a close friend)
      have all been shown to attenuate the impact of childhood abuse. In addition,
      there is great potential in the identification of genomic biomarkers to help
      guide us in the identification of traumatized individuals who are susceptible to
      depression. These indices may also help identify those for whom the immediate
      provision of treatment may have a preventive effect and may someday guide us in
      the development of novel pharmacologic approaches.

PMID- 22370491
TI  - The varieties of depressive experience: diagnosing mood disorders.
AB  - Biopsychosocial eclecticism has led, the authors believe, to a simplistic
      acceptance of a unitary view of MDD with little scientific solidity. The authors
      propose a return to careful psychopathology as the basis of all nosology, which
      has led to identifying four main types of depressive illness, and a method-based,
      existential approach to understanding depression.

PMID- 22370492
TI  - Treatment selection in depression: the role of clinical judgment.
AB  - The selection of treatment in depression should be filtered by clinical judgment,
      taking into consideration a number of clinical variables, such as characteristics
      and severity of depressive episode, co-occurring symptomatology and problems (not
      necessarily syndromes), medical comorbidities, and patient's history with
      particular reference to treatment of previous episodes, if they occurred. Such
      information should be placed within what is actually available in the specific
      treatment setting and should be integrated with the patient's preferences. In
      clinical practice, on the one end, clinical decisions may be affected by
      irrational factors (eg, exposure to massive doses of pharmaceutical propaganda or
      familiarity with a specific psychotherapy or medication). On the other end,
      psychiatrists often use sophisticated forms of clinical judgment that are
      suitable for clinical challenges but are not addressed by current research
      strategies. There is increasing awareness of the need of differentiating
      depression according to specific subtypes, yet clear-cut indications for these
      subdivisions are still missing. The role of biomarkers, despite many promising
      research strategies, is still far from offering reliable clinical guidance. In
      the meanwhile, there are important indications that come from clinical research.
      Treatment of depression may be conceptualized as integrated treatment of the
      various components of symptomatology, lifestyle, and social adjustment. An
      integrated treatment model, discussed in detail elsewhere, is realistic and
      practical, and not just idealistic. It may be frustrating to those who like
      oversimplified biological models; however, approaches that integrate
      clinimetrics, patient priorities, lifestyle issues, and clinical judgment are
      more in keeping with the complexity of clinical situations and the challenge of
      depression treatment.

PMID- 22370493
TI  - Cognitive behavioral therapy for depression.
AB  - CBT is a valuable treatment for mild, moderate, and severe forms of major
      depression. It is equally effective and more durable than medication alone, and
      the combination of medication and CBT may increase the response rate and extend
      durability when CBT is employed after pharmacotherapy is successful. Therapist
      competence has been shown to influence outcomes in CBT for depression.
      Practitioners who wish to learn more about CBT may access a wide variety of
      educational materials: basic texts, course offerings at major scientific
      meetings, and local and national training centers are available. The Academy of
      Cognitive Therapy website (www.academyofct.org) provides detailed information
      about obtaining training and certification in CBT.

PMID- 22370494
TI  - Psychodynamic treatment of depression.
AB  - Findings reviewed in this article show that PT should be included in treatment
      guidelines for depression. BPT in particular has been found to be superior to
      control conditions, equally effective as other active psychological treatments,
      with treatment effects that are often maintained in the long run, conferring
      resistance to relapse. Moreover, BPT is as effective as pharmacotherapy in the
      acute treatment of mild to moderate depression, and, either as monotherapy or
      combined with medication, BPT is associated with better long-term outcome
      compared with pharmacotherapy alone. PT is accepted by many depressed patients as
      a viable and preferred treatment. Furthermore, LTPT and PA have shown promise in
      treating patients with complex psychological disorders characterized by mood
      problems, often with comorbid personality problems. Finally, although studies
      suggest that effects of PT may be achieved somewhat slower compared with other
      forms of psychotherapy as well as medication in the acute treatment of
      depression, LTPT appears to be more clinically effective and perhaps more cost
      effective in the long run, particularly for chronically depressed patients. As
      noted, these conclusions need to be interpreted within the context of important
      limitations. Compared with other treatments, the evidence base for PT in
      depression remains relatively small, despite a respectable research tradition
      supporting psychodynamic assumptions with regard to the causation of depression.
      Moreover, and perhaps most importantly, although more studies now include longer
      follow-up assessments, our knowledge about the long-term effects of so-called
      evidence-based treatments of depression remains sketchy at best. In this context,
      the growing evidence for the efficacy and effectiveness of LTPT is promising.
      Overall, it is clear that the future of the treatment of depression may lie in a
      combined disorder- and person-centered, tailored-made approach, which takes into
      account, particularly in chronic depression, the broader interpersonal context
      and life history of the individual. It is clear that psychodynamic therapies have
      an important role to play in this respect.

PMID- 22370495
TI  - Evidence-based somatic treatment of depression in adults.
AB  - The efficacy of antidepressants has become a contentious topic over the last
      decade, and yet a review of the literature shows that they are consistently more
      effective than placebo. Although the average magnitude of this effect is unclear,
      many individual patients respond well to a course of antidepressants, and relapse
      when the medication is discontinued. Choosing the right antidepressant for a
      given patient remains more art than science, but the studies reviewed here
      provide some helpful guidance. Table 4 lists the second-generation
      antidepressants along with potential reasons for choosing one over the other
      (based on side effects, costs, or possible therapeutic advantages.) Based on
      these data, the following conclusions can be drawn: * For an all-around first
      line antidepressant, sertraline is hard to beat, given its combination of
      efficacy, tolerability, and low expense. Once escitalopram becomes generic, it
      will join sertraline in this category. * Bupropion is often a first-line
      alternative to sertraline, because of its lack of sexual side effects; although
      it has less efficacy for anxiety disorders, it is helpful for other
      comorbidities, such as tobacco dependence and attention-deficit/ hyperactivity
      disorder. * Both paroxetine and mirtazepine are often maligned because of side
      effects of sedation and weight gain; however, these side effects may be
      advantageous for those whose depressive symptoms include insomnia and excessive
      weight loss. * Although not specifically reviewed in this article, certain
      antidepressants are liable to cause more drug-drug interactions than others; the
      most prominent of these are fluoxetine, paroxetine, and fluvoxamine.

PMID- 22370496
TI  - How (not what) to prescribe: nonpharmacologic aspects of psychopharmacology.
AB  - Despite advances in psychopharmacology over the past several decades, treatment
      outcomes for depression have not substantially improved. Depression is not being
      eradicated. If anything, the evidence suggests that the problem of depression and
      treatment-resistant depression is growing, not shrinking. As biologically
      reductionistic approaches dominate psychiatric practice, patient care has steered
      away from considering the potent effects of meaning and relationships in the
      psychopharmacologic treatment of our patients. By construing patients as passive
      recipients of concrete, specific, and straightforward medical interventions, the
      field has succumbed to a delusion of precision, and unwittingly moved into an era
      of treatment resistance in which some of our most potent tools are wasted. In
      such a model we have settled for treating a disorder rather than a whole person.
      This article is intended as a step toward remedy. Meaning effects, therapeutic
      alliance, ambivalence, and patient autonomy, among others, have a powerful and
      measurable impact on the use of medication that should be considered if we are to
      treat the whole person. Bringing these elements together into a coherent model of
      treatment, however, is only a starting point. More research is needed if we are
      to understand the effects these elements have when used together in an integrated
      model that is simultaneously personalized and evidence-based.

PMID- 22370497
TI  - Combined treatment of depression.

PMID- 22370498
TI  - Child and adolescent depression: psychotherapeutic, ethical, and related
      nonpharmacologic considerations for general psychiatrists and others who
      prescribe.
AB  - Depression is a common, recurring disorder affecting millions of youth at some
      point before they reach mature adulthood. Given the shortage of and uneven
      distribution of psychiatrists who have completed specialized fellowships in child
      and adolescent psychiatry, a significant number of depressed youth will receive
      their pharmacotherapy from general psychiatrists and other prescribers with
      varying degrees of interest, training, and even willingness to treat children and
      adolescents. For general psychiatrists who will prescribe antidepressants for
      minors, knowledge of the training and expertise of nonphysician mental health
      professionals, the psychotherapies they may employ, and familiarity with school
      services are essential. Physicians who typically work only with adults will also
      need familiarity with differing ethical, legal, and regulatory issues and
      standards applicable to pediatric psychopharmacology. General psychiatrists,
      pediatricians, family physicians, nurse practitioners, and others contribute
      greatly to the care of depressed children, adolescents, and their families, and
      many find this work to be a very rewarding part of their professional practices.

PMID- 22370499
TI  - Depression in later life: an overview with treatment recommendations.
AB  - We have already entered a new, more exciting, and hopeful era in the treatment of
      late-life depression. The increasing numbers of older adults who are surviving to
      more advanced ages and the greater recognition of late-life depression's
      prevalence and impact on quality of life emphasize how important it is to detect
      and treat this disorder. Our increasing repertoire of evidence-based
      psychotherapeutic, pharmacologic, and neurotherapeutic treatment interventions
      offers many treatment alternatives, allowing substantial individualization of
      treatment approach. Demonstration of the effectiveness of depression treatment in
      primary care suggests the feasibility of increasing our patients' access to care.
      Growing appreciation of the pathophysiology of depression and its
      interrelationships with cognitive impairment may increase our ability to limit or
      delay certain aspects of cognitive impairment through more aggressive treatment
      of depression. Improved recognition and treatment of late-life depression holds
      great potential for improving physical and mental health in later life, reducing
      disability in later years, and improving quality of life.

PMID- 22370500
TI  - Depression in medically ill patients.
AB  - In medically ill patients, given the many entities the phenotype of depression
      may represent, clinicians must be prepared to cast their diagnostic nets widely,
      not settling for the obvious but frequently incorrect choice of major depressive
      episode and throwing antidepressants at it willy nilly. Having chosen the correct
      diagnosis from among a broad differential of depression "look-alikes," clinicians
      can draw upon a broad swath of treatment modalities including medications,
      psychotherapy, social supports, and spiritual interventions. Working as a
      psychiatrist in the medical arena requires the curiosity and analytic skills of a
      detective and the breadth of knowledge of a polymath adapting therapeutic tools
      from across the biopsychosociospiritual spectrum to the specific needs of the
      patient.

PMID- 22370501
TI  - Management of treatment-resistant depression.
AB  - Given the limitations of evidence for treatment options that are consistently
      effective for TRD and the possibility that TRD is in fact a form of depression
      that has a low probability of resolving, how can clinicians help patients with
      TRD? Perhaps the most important conceptual shift that needs to take place before
      treatment can be helpful is to accept TRD as a chronic illness, an illness
      similar to many others, one that can be effectively managed but that is not, at
      our present level of knowledge, likely to be cured. An undue focus on remission
      or even a 50% diminution of symptoms sets unrealistic goals for both patients and
      therapists and may lead to overtreatment and demoralization. The focus should be
      less on eliminating depressive symptoms and more on making sense of and learning
      to function better in spite of them. It is important to acknowledge the difficult
      nature of the depressive illness, to remove blame from the patient and clinician
      for not achieving remission, to set realistic expectations, and to help promote
      better psychosocial functioning even in the face of persisting symptoms. The
      critical element when implementing such an approach is a judicious balance
      between maintaining hope for improvement without setting unrealistic
      expectations. It is important to reemphasize that following a disease management
      model with acceptance of the reality of a chronic illness is not nihilistic and
      does not mean the abandonment of hope for improvement. The first step in treating
      a patient with TRD is to perform a comprehensive assessment of the patient's past
      and current treatment history to ensure that evidence-based treatment trials have
      in fact been undertaken, and if not, such treatment trials should be implemented.
      If the patient continues to have significant residual symptoms, it is important
      to determine the impact is of these symptoms on the patient's quality of life and
      ability to function. It is also important to evaluate the factors that may be
      contributing to the persistence of depressive symptoms such as comorbid
      personality disorders, somatic disorders, substance abuse, and work and
      interpersonal conflicts. The treatment of patients with TRD needs to move beyond
      attempts to modify symptoms without taking into consideration and attempting to
      modify the patient's personality, coping skills, and social system. Further
      somatic treatment trials can be undertaken, if desired by the patient and
      therapist, as a small (5%-15%) percentage of patients may respond and further
      treatment trials, and this may engender hope. The risk with this approach is that
      patients and therapists may not work at disease management skills if they believe
      there may be a resolution of the depression if they could just find the right
      medication or intervention. Therapists may also feel pressured by patients,
      families, insurance companies, as well as their own sense of helplessness to
      escalate treatment in a more and more aggressive manner in an attempt to achieve
      an elusive remission. A disease management program can provide the therapist and
      patient with sufficient structure, skills, and goals to encourage ongoing
      treatment without resorting to unproven measures that may create more side
      effects and problems. It is particularly important to include the patient's
      significant others in the reformulation of the patient's problem and thereby
      learn how to manage the illness more effectively. Significant others and family
      members can be invaluable in providing support for dealing with the difficult
      process of acquiring a new skill set. Indeed, they spend significantly more time
      with the patient than does any therapist. Family members are likely to provide
      this kind of support only if they have been part of the assessment and treatment
      process. Patients with a wide range of chronic medical illnesses can and do learn
      to function effectively and to achieve a satisfying quality of life in spite of
      their illness. There is no reason to think that patients with TRD should not be
      able to achieve a similar level of illness management, functioning, and quality
      of life.

PMID- 22370502
TI  - Integrative approaches to depression and its treatment.

PMID- 22370503
TI  - The interaction between duration, velocity and repetitive auditory stimulation.
AB  - Repetitive auditory stimulation (with click trains) and visual velocity signals
      both have intriguing effects on the subjective passage of time. Previous studies
      have established that prior presentation of auditory clicks increases the
      subjective duration of subsequent sensory input, and that faster moving stimuli
      are also judged to have been presented for longer (the time dilation effect).
      However, the effect of clicks on velocity estimation is unknown, and the nature
      of the time dilation effect remains ambiguous. Here were present a series of five
      experiments to explore these phenomena in more detail. Participants viewed a
      rightward moving grating which traveled at velocities ranging from 5 to 15
      degrees /s and which lasted for durations of 500 to 1500 ms. Gratings were
      preceded by clicks, silence or white noise. It was found that both clicks and
      higher velocities increased subjective duration. It was also found that the time
      dilation effect was a constant proportion of stimulus duration. This implies that
      faster velocity increases the rate of the pacemaker component of the internal
      clock. Conversely, clicks increased subjective velocity, but the magnitude of
      this effect was not proportional to actual velocity. Through considerations of
      these results, we conclude that clicks independently affect velocity and duration
      representations.

PMID- 22370504
TI  - Frequency of HLA-DRB1 gene alleles in patients with multiple sclerosis in a
      Lithuanian population.
AB  - The aim of the present study was to investigate the influence of HLA-DRB1 alleles
      on the genetic susceptibility to multiple sclerosis in the Lithuanian population.
      MATERIAL AND METHODS. A total of 120 patients with multiple sclerosis and 120
      unrelated healthy controls were enrolled in this case-control study. Allelic
      frequencies were compared between the groups. HLA-DRB1 alleles were genotyped
      using the polymerase chain reaction. RESULTS. HLA-DRB1*15 was present in 55.8% of
      the patients with multiple sclerosis and 10.0% of the controls (OR, 5.58; 95% CI,
      3.19-9.77; P<0.0001). The protective alleles that were found to be more prevalent
      among the controls compared with the patients with multiple sclerosis were HLA
      DRB1*01 (26.7% vs. 7.5%, P<0.0001), *03 (17.5% vs. 8.3%, P=0.034), and *16 (11.7%
      vs. 3.3%, P=0.014). HLA-DRB1*15 was more common among the female patients with
      multiple sclerosis than among the male patients (68.4% vs. 34.1%; OR, 4.18; 95%,
      CI 1.90-9.22; P=0.001). The heterozygous inheritance of HLA-DRB1*15 allele was
      more common in the patients with a history of maternal multiple sclerosis than in
      those with a history of paternal multiple sclerosis (29.4% vs. 9.8%; P=0.045).
      CONCLUSIONS. HLA-DRB1*15 was found to be associated with multiple sclerosis in
      the Lithuanian population. This allele was more prevalent among the female
      patients with multiple sclerosis. Maternal multiple sclerosis was more common
      than paternal multiple sclerosis, but the relationship with HLA-DRB1*15 allele
      was not established. HLA-DRB1*01, *03, and *16 appeared to be the protective
      alleles in this series.

PMID- 22370505
TI  - Clinical and pathological findings of fatal 2009-2010 pandemic influenza A (H1N1)
      infection in Estonia.
AB  - The aim of this study was to analyze all deaths from A (H1N1) in Estonia during
      the 2009-2010 epidemic to find out the reasons of high mortality and optimize
      management strategies for future influenza epidemics. MATERIAL AND METHODS. A
      retrospective review of medical records, autopsy reports, and reassessment of
      autopsy slides of all fatal cases of proven A (H1N1) influenza in Estonia from
      October 2009 to May 2010 was carried out. RESULTS. There were a total of 21
      proven fatal cases (median age, 57 years); the population mortality rate of 1.56
      per 100 000 inhabitants was one of the highest in the world. Altogether, 18 of
      the 21 patients had known risk factors for influenza, and 3 patients were
      previously healthy children. Three decedents had received antiviral treatment,
      and none had been immunized. There were 19 decedents autopsied, with viral
      pneumonia (58%) being the most frequent pathological finding; 40% had evidence of
      bacterial superinfection. In 4 cases, influenza was not clinically suspected and
      was diagnosed postmortem. Influenza was the primary cause of death in 15
      decedents, while in 9 cases, comorbidities played a significant role in fatal
      outcome. In the remaining 4 cases, another illness was considered the primary
      cause of death with influenza as an accompanying factor. CONCLUSIONS. High
      autopsy rate and liberal postmortem PCR testing enables the detection of
      additional A (H1N1) influenza cases, yet it might lead to overestimation of the
      population mortality rates, especially in a small population with low number of
      events. Increased vaccine coverage, vigilant diagnosing including wide PCR
      testing, and early more liberal use of antiviral medications during the influenza
      A (H1N1) epidemic may hold the potential of lowering population mortality.

PMID- 22370506
TI  - Primary epithelioid sarcoma of the neck: a rare case report.
AB  - This report presents a case of a neck epithelioid sarcoma in a 20-year-old man
      with poor prognosis. The patient underwent surgery followed by external beam
      radiotherapy and brachytherapy performed as a boost. The treatment was well
      tolerated, and there was no local recurrence or distant metastasis.

PMID- 22370507
TI  - Noninvasive monitoring of cerebrovascular autoregulation response to resistance
      exercises.
AB  - BACKGROUND AND OBJECTIVE. A novel noninvasive monitor is presented by
      demonstrating its capabilities to perform the real-time estimation of dynamics in
      cerebrovascular autoregulation in athletes during their training. The aim was to
      explore the characteristics of human cerebrovascular autoregulation by performing
      the monitoring of cerebrovascular autoregulation responses to resistance
      exercises in healthy volunteer athletes. MATERIAL AND METHODS. Cerebrovascular
      autoregulation status was monitored in 20 amateur and 20 elite male athletes
      (weightlifters and bodybuilders) in the supine position at rest during and after
      the resistance exercises by using a novel noninvasive monitor "Vittamed." Blood
      pressure and heart rate were also measured noninvasively. During the exercises,
      the athletes lifted 50 kg and 80% of 1RM (repetition maximum) weights in a
      dynamic and static manner in separate tests. RESULTS. The cerebrovascular
      autoregulation reactivity index showed a temporal improvement in the
      cerebrovascular autoregulation status for almost all sportsmen after the
      exercises. No disturbances of cerebrovascular autoregulation response occurred in
      the weightlifters and amateur athletes after the static and dynamic exercises.
      However, an unstable status of cerebrovascular autoregulation was observed for
      the elite bodybuilders during the interval of 400 to 600 s after the exercises.
      CONCLUSIONS. The data of this study demonstrated significant differences in
      cerebrovascular autoregulation response to the resistance exercises between the
      elite bodybuilders and other subjects (amateurs and weightlifters) - a
      temporarily unstable status of cerebrovascular autoregulation was observed in the
      group of elite bodybuilders. This study also demonstrated the applicability of
      the noninvasive device for exploring the physiology of cerebrovascular
      autoregulation mechanism in elite athletes and healthy volunteers.

PMID- 22370508
TI  - Myxomatous corneal degeneration: a clinicopathological study of six cases and a
      review of the literature.
AB  - Thirteen cases with myxomatous changes of the corneal stroma have been reported
      to date. We report six additional cases with clinical, histopathological, and
      immunohistochemical data. The clinical appearance is most often a gelatinous,
      whitish elevation with insidious onset. Histopathologically, there are
      inconspicuous spindle- and stellate-shaped cells in a loose, myxoid matrix. The
      typical location is in the anterior cornea beneath the epithelium, with varying
      degrees of extension into the stroma. Vimentin and smooth-muscle actin
      immunohistochemical stains are characteristically positive, and staining
      occasionally may be seen with muscle-specific actin, whereas CD34 staining
      usually is negative. In most cases, myxomatous changes are a degenerative process
      involving transformation of stromal keratocytes into cells with prominent
      secretory activity and myofibroblastic differentiation. Most occur in corneas
      with a history of ocular disease or trauma that disrupts Bowman's layer. We
      suggest labelling lesions with these features as "myxomatous corneal
      degeneration." So-called "primary corneal myxomas" also exist where there is no
      significant history. It remains unclear whether the myxomatous changes in such
      lesions are neoplastic or degenerative. Myxomatous corneal changes are likely
      under-recognized and under-diagnosed.

PMID- 22370509
TI  - Blood cells and their use in active immunotherapy of prostate cancer.
AB  - Immune therapy has traditionally had a limited role in the treatment of solid
      malignancies, outside of renal cancer and melanoma. However, early evidence of
      the ability to provoke an effective anti-tumor immune response in prostate cancer
      has led to interest in developing a variety of immune activating strategies in
      this disease. The first immune therapy to attain success in prolonging survival
      for metastatic prostate cancer patients is Sipuleucel-T. Rather than utilizing a
      typical vaccine approach in which antigens and immune activators are injected
      into the cancer host, sipuleucel-T was developed to stimulate autologous
      dendritic cells ex vivo, in order to evade the immune suppressive environment
      created by the cancer. We review the components of the immune system which may be
      harnessed in the development of immunotherapy in the setting of the recent
      success with sipuleucel-T.

PMID- 22370511
TI  - Group A rotavirus genotypes circulating prior to implementation of a National
      Immunization Program in Estonia.
AB  - Group A rotaviruses (RVA) are a major cause of acute gastroenteritis in children
      <= 5 y worldwide which could be prevented with two recently introduced vaccines -
      monovalent Rotarix (live-attenuated G1P[8] strain) and pentavalent RotaTeq (human
      bovine reassortant containing serotypes G1, G2, G3, G4 and P[8]). Prior to
      implementation of vaccines into national immunization program we aimed to
      describe RVA genotype distribution in hospitalized children aged < 5 y in Estonia
      during 2007-2008. A total of 671 children with confirmed RVA gastroenteritis from
      three major pediatric hospitals were prospectively enrolled. G- and P-genotypes
      were detected from 124 stool samples by semi-nested reverse transcription-PCR.
      Severity of disease was assessed using Clark scoring system. The majority of
      cases (65%) occurred in infants aged 7 to 24 mo and were of moderate severity
      (mean Clark score 12.1 (SD 3.2)). The prevailing strain was G2P[4] (34.7%),
      causing significantly more cases than G4P[8] (12.9%), G1P[8] or G9P[8] (both
      4.0%), G3P[8] (1.6%). Yearly differences in genotype distribution occurred, as
      G2P[4] (52.8%) dominated in 2007, but G4P[8] (26.9%) in 2008. One third of
      strains remained non-typeable. The distribution of RVA genotypes in Estonia
      differs from that seen in other Central and Eastern European countries, although
      one should bear in mind the large proportion of P-untypeable strains and natural
      fluctuations of dominating RVA genotypes. Nevertheless, considering the high
      genotype-independent efficacy of the vaccines, introduction of national
      immunization should be considered.

PMID- 22370510
TI  - Glycoconjugate vaccine strategies for protection against invasive Salmonella
      infections.
AB  - Salmonella enterica serovars Typhi and Paratyphi A and B and certain non
      typhoidal Salmonella enterica (NTS) serovars are important causes of invasive
      Salmonella disease worldwide. NTS serovars Typhimurium and Enteritidis typically
      cause gastroenteritis in healthy children and adults in industrialized countries
      but in certain hosts (e.g., young infants, the elderly, immunocompromised
      individuals) they also cause invasive infections. These two serovars also cause
      invasive disease in infants and young children in sub-Saharan Africa. Whereas
      Salmonella surface polysaccharides are poor immunogens in animal models and do
      not generate immunologic memory, conjugation with carrier proteins overcomes
      these limitations. S. Typhi expresses a Vi polysaccharide capsule; Vi either
      alone or as a glycoconjugate protects humans from typhoid fever. In contrast, S.
      Paratyphi A and B and NTS (with rare exceptions) do not express capsular
      polysaccharides. Rather, their surface polysaccharides are the O polysaccharide
      (OPS) of lipopolysaccharide. In animal studies, immunization with Salmonella COPS
      (core polysaccharide-OPS) conjugated with carrier proteins generates functional
      immunity and protects against fatal Salmonella challenge. Conjugating to
      Salmonella proteins (flagellin, porins) may extend immune responses to another
      relevant target for antibody generation and enhance the glyconjugate's efficacy.

PMID- 22370512
TI  - Subcutaneous immunization with recombinant adenovirus expressing influenza A
      nucleoprotein protects mice against lethal viral challenge.
AB  - Current influenza vaccines mainly induce strain-specific neutralizing antibodies
      and need to be updated each year, resulting in significant burdens on vaccine
      manufacturers and regulatory agencies. Genetic immunization strategies based on
      the highly conserved nucleoprotein (NP) of influenza have attracted great
      attention as NP could induce heterosubtypic immunity. It is unclear, however,
      whether different forms of vectors and/or vaccination regimens could have
      contributed to the previously reported discrepancies in the magnitude of
      protection of NP-based genetic vaccinations. Here, we evaluated a plasmid DNA
      vector (pNP) and a recombinant adenovirus vector (rAd-NP) containing the NP gene
      through various combinations of immunization regimens in mice. We found that pNP
      afforded only partial protection even after 4 injections, with full protection
      against lethal challenge achieved only with the fourth boost using rAd-NP.
      Alternatively, only two doses of rAd-NP delivered subcutaneously were needed to
      induce an enhanced immune response and completely protect the animals, a finding
      which, to our knowledge, has not been reported before.

PMID- 22370513
TI  - Hepatitis B vaccination failure in children with diabetes mellitus? The debate
      continues.
AB  - BACKGROUND: The aim of our study was to evaluate the presence of specific
      antibodies against HBsAg in diabetic children (IDDM) previously vaccinated
      against hepatitis B virus. PATIENTS AND METHODS: 110 diabetic children were
      retrospectively studied and 100 healthy controls were recruited. In all patients
      surface antigen, HBV core IgG, antibodies against HBV "e" antigen and
      quantitative HBV surface antibodies were detected. In 45 patients molecular
      typing of HLA alleles was performed. Metabolic control was evaluated as mean
      glycated hemoglobin (HbA1c) and all patients were compliant to insulin therapy.
      RESULTS: 46 of 110 diabetic children (41.8%) and 16 of 100 healthy controls (16%)
      were found to have not anti-HBs antibodies (p < 0.0001). The mean antibody titer
      was found significantly-lower (p < 0.0001) in IDDM children than healthy
      controls. No correlation was found between antibody titer, age, duration of
      disease and HbA1c. We did not find any difference of gender, age, years of onset
      of the disease and metabolic control, between diabetics with anti-HBs antibodies
      and those without. CONCLUSIONS: Our data confirm the reduced seroprotection rate
      for HBV vaccination in diabetics. However it remains poorly clarify the real
      clinical significance of this result. In our study no diabetic children showed
      markers of HBV infection.

PMID- 22370514
TI  - Formulation development of a plant-derived H1N1 influenza vaccine containing
      purified recombinant hemagglutinin antigen.
AB  - Influenza is a prevalent, highly contagious and sometimes fatal respiratory
      disease. Vaccination provides an effective approach to control the disease, but
      because of frequent changes in the structure of the major surface proteins, there
      is great need for a technology that permits rapid preparation of new forms of the
      vaccine each year in sufficient quantities. Recently, using a safe, simple, time-
      and cost-effective plant viral vector-based transient expression system, the
      hemagglutinin antigen of H1N1 influenza A strain (HAC1), an H1N1 influenza
      vaccine candidate, has been produced in Nicotiana benthamiana plants. As a step
      toward the generation of a commercially viable subunit influenza vaccine, we
      developed HAC1 formulations in the presence and absence of an aluminum salt
      adjuvant (Alhydrogel((r))), analyzed their properties, and assessed
      immunogenicity in an animal model. Biophysical properties of HAC1 were evaluated
      using several spectroscopic and light scattering techniques as a function of pH
      and temperature combined with data analysis using an empirical phase diagram
      approach. Excipients that were potent stabilizers of the recombinant protein were
      identified using intrinsic fluorescence spectroscopy. The adsorptive capacity and
      thermal stability of the protein on the surface of Alhydrogel((r)) were then
      examined in the presence and absence of selected stabilizers using UV absorbance
      after centrifugation and intrinsic fluorescence spectroscopy, respectively.
      Immunogenicity studies conducted in mice demonstrated that the highest level of
      serum immune responses (hemagglutination-inhibiting antibody titers), with a 100%
      seropositive rates, were induced by HAC1 in the presence of Alhydrogel((r)), and
      this response was elicited regardless of the solution conditions of the
      formulation.

PMID- 22370515
TI  - Cutaneous necrotic ulceration due to BCG re-vaccination.
AB  - The case report describes a severe local reaction with large cutaneous necrotic
      ulcer following bacillus Calmette-Guerin (BCG) re-vaccination. This is a very
      rare adverse event, and only a few reports have been described in the literature.

PMID- 22370516
TI  - Pandemic influenza hospitalization in Spain (2009): incidence, in-hospital
      mortality, comorbidities and costs.
AB  - Based on data drawn from the national hospitalization discharge registry, we
      sought to describe the clinical and epidemiological characteristics of patients
      hospitalized with pandemic influenza H1N1 in Spain in 2009. Authors calculated
      national rates of hospitalization stratified by age and analyzed co-morbidities,
      in hospital mortality, average length of stay and associated medical costs. A
      total of 11,449 patients were hospitalized (24.9/100,000 inhabitants). Median age
      was 34 y and 50.28% were male. The highest incidence was observed in the group
      from 0 to 14 y (42.3/100000 inhabitants), 27.7% of hospitalized women of
      childbearing age were pregnant and overall in hospital mortality reached 2.46%.
      The average length of stay was 5 d, median costs per admission was ?2,152 and
      total cost was ?35.4 million. Among those patients, 5,791 (50.6%) had an
      underlying chronic disease: asthma (15.36%), diabetes (9.02%), obesity (8.47%),
      cancer (4.47%), epilepsy (2.24%), and HIV (2.22%). Suffering a chronic condition
      was an independent risk factor for dying (OR 13.31 95% for 0-14 y and OR 3.27 for
      15-64 y). We conclude that hospitalization was higher in infants and in young
      adults with associated co-morbidities. Suffering a chronic condition increased
      the risk of dying as the age decreased. This information will be helpful to
      prepare vaccination strategies against next pandemic threats.

PMID- 22370517
TI  - Japanese encephalitis vaccine: need of the hour in endemic states of India.
AB  - Japanese encephalitis (JE), a mosquito-borne arboviral infection, is the leading
      cause of viral encephalitis in Asia. Most worldwide cases of JE are reported
      annually from the People's Republic of China (PRC), Korea, Japan, Southeast Asia,
      the Indian subcontinent, and parts of Oceania. JE virus is transmitted by Culex
      mosquitoes particularly of the Culex vishnui group (C. tritaeniorhynchus). Humans
      get infected following a bite by an infected mosquito. However, since humans
      cannot transmit infection, further spread does not take place between humans.
      Most human cases of JE are asymptomatic. Infection leads to overt encephalitis in
      only 1 of 20-1,000 cases. Encephalitis usually is severe, resulting in a fatal
      outcome in 25% of cases and residual neuropsychiatric sequelae in 30% of cases.
      The World Health Organization (WHO) estimates that there are at least 50,000
      serious cases of the disease in Asia each year. Approximately 10,000 of those
      subjects die, mostly children. JE Outbreaks have been reported from most states
      and union territories in India through the years. In India, the risk is highest
      in the monsoon and post-monsoon period. The proposed immunization strategy for
      India is based on the regional experience and builds off of the three pillars of
      JE control, i.e., Surveillance for cases of encephalitis, Vector control and
      Vaccination. The Cell Culture Derived Live SA-14-14-2 Vaccine is based on a
      stable neuro-attenuated strain of JE virus (SA-14-14-2). It was first licensed
      for use in 1988 in People's Republic of China, and current usage is over 60
      million doses per year. It is also licensed in India, South Korea and Nepal. JE
      vaccines are available in 5-dose vials as a lyophilized powder that looks like a
      milky-white crisp cake; this is rehydrated with 2.5 mL diluent. The dose is 0.5
      mL administered subcutaneously for all ages and containing not less than 5.4 log
      PFU of live JE virus (JEV).

PMID- 22370518
TI  - Mtb9.9 protein family: an immunodominant antigen family of Mycobacterium
      tuberculosis induces humoral and cellular immune responses in mice.
AB  - Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. This
      study evaluated the immune response in mice to members of the Mtb9.9 protein
      family. C57BL/6 mice were immunized with four different Mtb9.9 recombinant
      proteins to evaluate the humoral and cellular immune responses to each protein.
      Mouse splenocytes from these mice were stimulated in vitro for 72 h with the
      Mtb9.9 proteins. Concentrations of the cytokines interferon (IFN)-gamma and tumor
      necrosis alpha (TNF-alpha) in the culture supernatants were increased compared
      with controls. Sera were taken from the same mice at 3 weeks after immunization
      and contained significantly higher levels of immunoglobulin (Ig)G2c antibody when
      compared with sera from control mice. Our findings indicate a bias toward T
      helper (Th)1-type cellular and humoral memory responses against Mtb9.9
      recombinant proteins in mice. This study demonstrates that these proteins might
      be suitable candidates for use as subunit vaccines.

PMID- 22370519
TI  - What counts in cytometric analysis to document vaccine immunogenicity?
AB  - Studies on vaccines and infectious diseases are increasingly adding immune
      cytometry (for e.g., flow cytometry or ELISPOT assays) to the routine use of
      antibody titers as a way to report immunogenicity. We advocate that the classical
      presentation of cytometric data in terms of percentages should best be
      supplemented by an absolute cell count per ml. We do this by discussing a simple
      hypothetical example illustrating that without knowledge of the absolute cell
      count per ml detection competition will render a correct comparison between
      different samples impossible in all situations where an inter-individual or intra
      individual (longitudinal) variation in peripheral blood mononuclear cell
      concentrations is present.

PMID- 22370520
TI  - An overview of sipuleucel-T: autologous cellular immunotherapy for prostate
      cancer.
AB  - Sipuleucel-T, the first autologous active cellular immunotherapy approved by the
      United States Food and Drug Administration, is designed to stimulate an immune
      response to prostate cancer. Sipuleucel-T is manufactured by culturing a
      patient's peripheral blood mononuclear cells (including antigen presenting cells)
      with a recombinant protein comprising a tumor-associated antigen (prostatic acid
      phosphatase) and granulocyte-macrophage colony stimulating factor. Treatment
      consists of 3 infusions at approximately 2-week intervals, resulting in a prime
      boost pattern of immune activation, a robust antigen-specific cellular and
      humoral immune response, and, consequently, a survival benefit in subjects with
      asymptomatic or minimally symptomatic metastatic castrate resistant prostate
      cancer. Adverse events are generally mild to moderate and resolve within 2 d.
      Serious adverse events occur at a low rate. As the first autologous cellular
      immunotherapy to demonstrate a survival benefit, sipuleucel-T is a novel
      oncologic therapeutic that warrants the reassessment of the current prostate
      cancer treatment paradigm.

PMID- 22370521
TI  - Positive drinking consequences among hazardous drinking college students.
AB  - Negative drinking consequences in college students have been well studied, but
      emerging evidence points to a role for positive drinking consequences in
      predicting alcohol related problems. Positive drinking consequences appear to be
      distinct from other drinking constructs such as drinking expectancies and
      drinking motives. However, no work has evaluated the role of positive drinking
      consequences in hazardous drinking college students, a population at high risk
      for alcohol related problems. The goal of the current study was to examine the
      effect of positive drinking consequences on problem drinking and alcohol problem
      recognition in a hazardous drinking college sample. Participants (N=222) were
      hazardous drinking undergraduate students completing a battery of self-report
      measures about alcohol use. Findings indicated that positive drinking
      consequences predicted problem drinking above and beyond other related constructs
      including positive drinking motives (i.e. enhancement and social). However,
      positive drinking consequences did not appear to play a significant role in
      alcohol problem recognition. Future research directions and implications for
      interventions with hazardous drinking college students are discussed.

PMID- 22370522
TI  - Smoking behavior and motivational flexibility in light and heavy smokers.
AB  - Little is known about the consistency of people's reasons for smoking and how
      these might influence the amount of smoking in individuals. Therefore, we
      developed a new concept, motivational flexibility, which suggests that a behavior
      is more common when people have multiple reasons for engaging in it and when the
      primary reason changes across occurrences of the behavior. The purpose of this
      study was to examine motivational flexibility in cigarette smokers. We
      hypothesized that smoking would be associated with greater number of reasons for
      smoking and greater frequency of change (shifting) in the most important motive
      for smoking among light smokers. Student cigarette smokers (N=116) completed
      daily entries for 14 days: whether they smoked or not and their reasons for doing
      so, with importance ratings for each reason listed. Multilevel modeling was used
      to examine the relationship between motivational flexibility and daily cigarette
      smoking. Shifting among the most important motive over the 14-day assessment was
      associated with greater frequency of smoking in light but not daily smokers.
      Also, smoking for craving and social reasons was associated with smoking fewer
      cigarettes and on fewer days. Results confirm the applicability of the
      motivational flexibility concept to smoking. The association between motive
      shifting and greater frequency of smoking may indicate a greater responsiveness
      to environmental cues. That we found this association in light but not daily
      smokers who are likely addicted to cigarettes may indicate that light smokers are
      affected more by triggers for smoking, or that they may rationalize their smoking
      behavior more than heavier smokers.

PMID- 22370523
TI  - Smokers: at risk for prostate cancer but unlikely to screen.
AB  - Prostate cancer is the most commonly diagnosed cancer in men. Evidence suggests
      that smokers may be at increased risk of prostate cancer compared to non-smokers.
      In the present study we ask whether adult men who smoke are also less likely to
      undergo screening for prostate cancer. Adult men aged 46 and above completed a
      single questionnaire including demographic items and items concerning their
      smoking status and previous testing for prostate cancer. The questionnaire also
      included an 11 item numeracy scale. Compared to smokers, non-smokers and ex
      smokers were around two times more likely to have undergone screening for
      prostate cancer, and had been tested more frequently. Smokers are not only more
      likely to develop prostate cancer, they are, paradoxically, less likely to
      undergo screening for prostate cancer. Health care professionals need to be
      cognizant of individual differences in screening behavior and that smokers have a
      reduced likelihood of choosing to screen.

PMID- 22370524
TI  - Phenolics, flavonoids, antioxidant activity and cyanogenic glycosides of organic
      and mineral-base fertilized cassava tubers.
AB  - A field study was conducted to determine the effect of organic and mineral-based
      fertilizers on phytochemical contents in the tubers of two cassava varieties.
      Treatments were arranged in a split plot design with three replicates. The main
      plot was fertilizer source (vermicompost, empty fruit bunch compost and inorganic
      fertilizer) and sub-plot was cassava variety (Medan and Sri Pontian). The amount
      of fertilizer applied was based on 180 kg K(2)O ha-1. The tubers were harvested
      and analyzed for total flavonoids, total phenolics, antioxidant activity and
      cyanogenic glucoside content. Total phenolic and flavonoid compounds were
      determined using the Folin-Ciocalteu assay and aluminium chloride colorimetric
      method, respectively. Different sources of fertilizer, varieties and their
      interactions were found to have a significant effect on phytochemical content.
      The phenolic and flavonoid content were significantly higher (p < 0.01) in the
      vermicompost treatment compared to mineral fertilizer and EFB compost. The total
      flavonoids and phenolics content of vermicompost treated plants were 39% and 38%
      higher, respectively, than those chemically fertilized. The antioxidant activity
      determined using the DPPH and FRAP assays were high with application of organic
      fertilizer. Cyanogenic glycoside levels were decreased with the application of
      organic fertilizer. Among the two types of compost, vermicompost resulted in
      higher nutritional value of cassava tubers. Medan variety with application of
      vermicompost showed the most promising nutritional quality. Since the nutritional
      quality of cassava can be improved by organic fertilization, organic fertilizer
      should be used in place of chemical fertilizer for environmentally sustainable
      production of better quality cassava.

PMID- 22370525
TI  - Production of salvianolic acid B in roots of Salvia miltiorrhiza (Danshen) during
      the post-harvest drying process.
AB  - Drying is the most common and fundamental procedure in the post-harvest
      processing which contributes to the quality and valuation of medicinal plants.
      However, attention to and research work on this aspect is relatively poor. In
      this paper, we reveal dynamic variations of concentrations of five major
      bioactive components, namely salvianolic acid B (SaB), dihydrotanshinone I,
      cryptotanshinone, tanshinone I and tanshinone IIA, in roots of Salvia
      miltiorrhiza (Dashen) during the drying process at different oven temperatures. A
      minor amount of SaB was found in fresh materials while an noticeable increase in
      SaB was detected in drying at 50~160  degrees C. The maximal value occurred after
      40 min of drying at 130  degrees C and its variation showed a reverse V-shaped
      curve. Production of SaB exhibited a significant positive correlation with drying
      temperatures and a significant negative correlation with sample moistures. The
      amounts of tanshinones were nearly doubled in the early stage of drying and their
      variations showed similar changing trends with drying temperatures and sample
      moistures. The results supported our speculation that postharvest fresh plant
      materials, especially roots, were still physiologically active organs and would
      exhibit a series of anti-dehydration mechanisms including production of related
      secondary metabolites at the early stage of dehydration. Hence, the proper design
      of drying processes could contribute to promoting rather than reducing the
      quality of Danshen and other similar medicinal plants.

PMID- 22370526
TI  - Exercise-induced bronchoconstriction: burden and prevalence.
AB  - Exercise-induced bronchoconstriction (EIB) is common in asthma patients as well
      as athletes. This article provides an overview of the prevalence and impact on
      quality of life (QoL) of EIB based on an analysis review of selected literature.
      The term EIB is preferred to exercise-induced  asthma because EIB does not cause
      asthma, and asthma is not a prerequisite to have EIB. EIB is extremely common in
      asthma patients and is reported in most asthma patients. Several factors may
      increase the prevalence of EIB including severity of asthma, family history of
      asthma, atopy, respiratory  infections, and urbanization. Some studies also
      suggest EIB is more common in girls than boys and in younger-age children. EIB
      also occurs in athletes, even without asthma. The prevalence of EIB varies among
      sports with some of the highest rates observed in Nordic combined, cross-country,
      and short track Winter Olympic athletes. Environmental factors may have a role
      in EIB including chlorine in swimmers and particulate matter exposure from fossil
      fueled ice resurfacing machines in ice arena athletes. Accumulating evidence
      indicates that the burden of EIB impairs QoL. EIB is  a common condition in
      asthma patients and athletes and adversely affects the QoL and the ability to
      participate in sports.

PMID- 22370527
TI  - Coexistence of allergic diseases: patterns and frequencies.
AB  - The atopic march hypothesis suggests that allergy diseases often progress from
      atopic dermatitis to allergic asthma, and allergic rhinitis. How often can the
      classic progression of allergic diseases be observed in the pediatric patient
      population? This study aimed to observe the pattern  of allergic diseases
      progression, onset age, disease intervals, and frequency of the allergic march.
      Data from the National Health Insurance Research Database in the period 1996-2008
      were used to obtain a cohort of children with allergic disease. Physician's
      diagnosis was used to confirm  the allergic disease based on the international
      disease coding. The age of disease onset was compared. There were 10,729 children
      aged <5 years enrolled from the 200,000 individuals randomly sampled in 2000. Of
      these, 5866 (54.7%) had been diagnosed with at least one allergic disease. The 
      rate of only one of three diseases diagnosed was 29.8% (3195 patients), whereas
      18.8% had two allergic diseases and 6.1% had all three allergic diseases. Only
      4.2% of cases matched the allergic march. Patients with more than one disease had
      earlier onset age than those who had only one disease  (4.17 versus 2.79 and 2.32
      years old; p < 0.05). The allergic march accounts for only 4.2% in this study. A
      patient with only one allergic disease after the age of 4.17 years will not have
      another allergic disease until the age of 12 years. However, a patient with an
      allergic disease before  2.79 years old will probably have another allergic
      disease in 1.96-2.5 years.

PMID- 22370528
TI  - A forced expiratory flow at 25-75% value <65% of predicted should be considered
      abnormal: a real-world, cross-sectional study.
AB  - Forced expiratory volume in 1 second (FEV1) is considered an important parameter
      for asthma diagnosis and follow-up. However, it has been proposed that forced
      expiratory flow at 25-75% (FEF(25-75)) could be more sensitive than FEV1 to
      detect slight airways obstruction. In this regard, a cutoff FEF(25-75) value has
      been recently established in a group of asthmatic children: FEF(25-75) < 65% of
      predicted has been considered impaired. However, the considered population was
      specifically selected. Therefore, the aim of the present study was to confirm an
      FEF(25-75) cutoff value in a large cohort of asthmatic children. Seven hundred
      allergic children (493 male subjects; median age, 11 years) with controlled and
      partly controlled asthma were evaluated by performing spirometry and skin-prick
      tests. Three hundred thirteen (44.7%) patients had FEF(25-75%) values of <65% of
      predicted. Two predictors were significantly associated with impaired FEF(25-75)
      values: (i) sensitization to perennial allergens (adjusted odds ratio [OR(Adj)],
      3.4) and (ii) FEV(1) <= 86% of predicted (OR(Adj), 3.8). This study, conducted in
      real life, could suggest that FEF(25-75) value of <65% of predicted may be
      considered abnormal.

PMID- 22370529
TI  - Exercise-induced bronchoconstriction update: therapeutic management.
AB  - Management of exercise-induced bronchoconstriction (EIB) should include both
      prevention and treatment directed toward the underlying asthma and bronchial
      hyperresponsiveness. Both nonpharmacologic and pharmacologic approaches should be
      followed. Preexercise warm-up, to take advantage  of the refractory period that
      follows EIB, is an important preventive technique. Dietary interventions such as
      fish oil, vitamin D, and ascorbic acid have shown promising results. Beta 2
      agonists are considered the most effective agents for EIB at this time but
      intermittent use is recommended  to avoid tolerance or decreased effectiveness
      with daily regular use. Leukotriene inhibitors and mast cell stabilizing agents
      can be useful in EIB but are less effective than beta 2-agonists. Tolerance to
      beta 2-agonists is not prevented by concomitant use of inhaled corticosteroid but
      it  is not known whether use of leukotriene inhibitors can affect tolerance. EIB
      in elite athletes with no underlying asthma may have a different pathogenesis.

PMID- 22370530
TI  - Efficacy and tolerability study of ciclesonide nasal aerosol in patients with
      perennial allergic rhinitis.
AB  - A new nasal aerosol solution formulation of ciclesonide containing a
      hydrofluoroalkane propellant (CIC-HFA) delivered via a metered-dose inhaler is
      currently in clinical development as a potential treatment for allergic rhinitis
      (AR). This study evaluated the efficacy and tolerability of CIC-HFA 74- or 148
      microgram doses compared with placebo in patients with perennial AR (PAR).
      Patients >=12 years of age with a >= 2-year history of PAR were randomized in a
      placebo-controlled, double-blind, parallel-group, multicenter study to CIC-HFA 74
      micrograms, CIC-HFA 148 micrograms, or placebo q.d. in the morning (A.M.) for 26
      weeks. Change from baseline in reflective total nasal symptom score (rTNSS),
      instantaneous total nasal symptom score (iTNSS), and rhinoconjunctivitis quality
      of-life questionnaire with standardized activities (RQLQ[S]) in patients with
      baseline RQLQ of >=3.00 were evaluated for the first 6 weeks of treatment.
      Treatment-emergent adverse events (TEAEs) were monitored throughout the study.
      Eleven hundred eleven patients were randomized. CIC-HFA 74- and 148-microgram
      doses showed statistically significant improvements in rTNSS (least squares [LS]
      mean change, 0.70 and 0.54, respectively; p <= 0.001 versus placebo for both),
      iTNSS (LS mean change, 0.58 and 0.42, respectively; p < 0.05 versus placebo for
      both), and RQLQ[S] (LS mean change, 0.55 and 0.37, respectively; p < 0.01 versus
      placebo for both) from baseline. The overall incidence of TEAEs was comparable
      between the CIC-HFA treatment groups and placebo. In this study, once-daily
      treatment with CIC-HFA 74- or 148-micrograms showed statistically significant
      improvements in nasal symptoms of PAR. Both doses were well tolerated. Clinical
      trial registration URL and registration number:
      www.clinicaltrials.gov/ct2/show/NCT00953147.

PMID- 22370531
TI  - A study of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol
      in patients with seasonal allergic rhinitis from mountain cedar pollen.
AB  - A nasal aerosol formulation of ciclesonide with a hydrofluoroalkane propellant
      (CIC-HFA) is currently in development for treatment of allergic rhinitis (AR).
      This study evaluated the efficacy and safety of once-daily administration of CIC
      HFA 74 or 148 micrograms compared with placebo  in patients with seasonal AR
      (SAR) from mountain cedar pollen. Patients >=12 years of age with a >=2-year
      history of SAR from mountain cedar pollen were randomized in a placebo
      controlled, double-blind, parallel group, multicenter study to CIC-HFA 74
      micrograms, CIC-HFA 148 micrograms,  or placebo once daily in the morning for 2
      weeks. Change from baseline in reflective total nasal symptom score (rTNSS),
      instantaneous TNSS (iTNSS), and reflective total ocular symptom score (rTOSS) in
      patients with baseline rTOSS >=5.00 were evaluated. Adverse events (AEs) were
      monitored  throughout the study. A statistically significant improvement in rTNSS
      (least squares [LS] mean change from baseline 1.04 and 1.02 respectively; p <
      0.0001 versus placebo for both) and iTNSS (LS mean change from baseline 0.90 and
      0.83 respectively; p < 0.001 vs placebo for both) was  observed after treatment
      with CIC-HFA 74- or 148-microgram doses. Only the CIC-HFA 74-micrograms treatment
      group showed a statistically significant improvement in rTOSS (LS mean change
      from baseline 0.52; p = 0.0124) compared with placebo. The overall incidence of
      AEs was low and comparable  between the treatment groups. In this study,
      statistically significant improvements in nasal symptoms of SAR were observed
      after treatment with CIC-HFA 74-microgram or CIC-HFA 148-microgram doses. Both
      active treatments were well tolerated. Clinical trial registry URL and
      registration number:  www.clinicaltrials.gov/ct2/show/NCT01010971.

PMID- 22370532
TI  - Immunoglobulin E monitoring and reduction of omalizumab therapy in children and
      adolescents.
AB  - Omalizumab, a monoclonal anti-immunoglobulin E (IgE) antibody, is being
      successfully used as supplementary therapy to improve asthma control in children
      with severe persistent allergic asthma from the age of >=6 years. Because the
      majority of commercially available IgE assays  measure free as well as omalizumab
      bound IgE, a rise in total IgE is believed to occur in the course of therapy. We
      aimed at testing the therapeutic monitoring regime based on total IgE
      measurements in patients treated with omalizumab over a period of 12-60 months.
      We report on 10 patients  aged 8-17 years who were given omalizumab to treat
      severe allergic bronchial asthma. Total IgE in serum (sandwich immunoassay ADVIA
      Centaur; Siemens Healthcare Diagnostics GmbH, Eschborn, Germany) was determined
      before injection of omalizumab. In two patients, the dose of omalizumab  was
      reduced during the treatment once the patients' total IgE was in the normal
      range. Six months after the start of treatment with omalizumab, all patients
      showed a marked drop in total IgE levels compared with baseline (p < 0.003). All
      patients tolerated omalizumab well. The dose reduction  in two patients with
      normal total IgE levels caused no clinical deterioration. The rise in total IgE
      levels after treatment with omalizumab, which has been reported in the
      literature, was not confirmed in the present study. Extensive elimination of IgE
      by omalizumab influences the immune system  and IgE regulation. This will be an
      important aspect of dosage in long-term therapy. Patients undergoing treatment
      with omalizumab must be monitored at close intervals.

PMID- 22370533
TI  - Total serum IgE levels and atopic status in patients with sarcoidosis.
AB  - To date, two studies have reported lower total serum immunoglobulin E (IgE)
      levels and lower prevalence of atopy in patients with sarcoidosis compared with
      healthy subjects. However, those reports did not consider age or gender
      differences between cases and controls. In addition, the  association between
      total serum IgE levels and clinical manifestations of sarcoidosis has not been
      clarified. This study assessed total serum IgE levels and prevalence of atopy in
      patients with sarcoidosis after taking age and sex differences into account and
      evaluated associations between  total serum IgE levels and clinical
      manifestations of sarcoidosis. Total serum IgE levels and prevalence of atopy on
      initial visits were compared between 189 patients with sarcoidosis and 378 age-
      and sex-matched controls. Associations between total serum IgE levels and
      involvement of each  affected organ were evaluated. Changes in total serum IgE
      levels during the clinical course of sarcoidosis were also evaluated. Total serum
      IgE levels were significantly lower in patients with sarcoidosis than in
      controls, independent of atopic status (atopic subjects, p = 0.025; nonatopic 
      subjects, p < 0.001). Total serum IgE levels did not differ according to the
      involvement of different organs. Total serum IgE levels decreased further, albeit
      only slightly, after disease remission (p < 0.001). Increased susceptibility to
      sarcoidosis may be attributable to several underlying  genetic or environmental
      factors that result in lower total serum IgE levels.

PMID- 22370534
TI  - Changes in prevalence and characteristics of IgE-mediated food allergies in
      children referred to a tertiary care center in 2003 and 2008.
AB  - Although epidemiological trends in peanut allergy have been determined, there are
      limited data for changes in prevalence and clinical characteristics for other
      common food allergens. This study was performed to determine the trends in
      prevalence and clinical characteristics of physician-diagnosed  pediatric food
      allergy (FA) at a large urban-based tertiary care center from 2003 to 2008. The
      electronic medical record system was searched to identify all unique patients
      with FA as a diagnosis for 2003 and 2008. Included patients had either a definite
      clinical reaction on ingestion and  (1) a positive specific IgE or skin-prick
      test or (2) food-specific IgE of >90% specificity. Patients with allergies to
      cow's milk, eggs, fish, peanuts, sesame, shellfish, soy, tree nuts, and wheat
      were included. The percentage of FA clinic patients increased from 3 to 8% over 5
      years.  The severity of initial reactions to food also increased from 2003 to
      2008 (p < 0.05). Mean initial food-specific IgE decreased from 52 kU/L in 2003 to
      40 kU/L in 2003 (p = 0.002). The age at diagnosis decreased from 2003 to 2008 for
      cow's milk (2.64-1.36 years; p < 0.05) and  fish (5.10-2.86 years; p < 0.05)
      allergies. Peanuts and shellfish were associated with anaphylaxis and severe
      symptoms in 2008. Clinical characteristics of food-allergic reactions in this
      large tertiary care center worsened in severity over 5 years and reactions were
      associated with  a lower specific IgE at presentation for peanut and shellfish
      allergy. Clinical presentation of FA may change over time and this phenomenon
      warrants study to determine contributory factors.

PMID- 22370535
TI  - Pranlukast dry syrup inhibits symptoms of Japanese cedar pollinosis in children
      using OHIO Chamber.
AB  - Pranlukast (PLK) is a leukotriene receptor antagonist (LTRA) that has been
      approved for treatment of asthma in patients of all ages and allergic rhinitis
      (AR) in adults but not for AR in children in Japan. This randomized, double
      blind, placebo-controlled, crossover study used an artificial  exposure chamber
      (OHIO Chamber) to investigate the efficacy and safety of PLK in children from 10
      to 15 years old with seasonal AR (SAR) due to Japanese cedar (JC) pollen. Eighty
      four subjects were enrolled and randomized to the treatment arm and 74 were
      included in the per protocol set. Subjects  received either PLK dry syrup (DS) or
      placebo for 1 week. They were challenged with JC pollen in the OHIO Chamber for 3
      hours. Total nasal symptom scores (TNSSs) were recorded every 30 minutes during
      the exposure. PLK DS treatment suppressed the TNSS changes from baseline
      significantly when  compared with placebo. The difference in the least square
      means in TNSS between the PLK DS-treated group and placebo group was -0.37 (95%
      CI, -0.54, -0.20) with a value of p < 0.0001, showing that PLK DS significantly
      suppressed the nasal symptoms. Regarding specific  nasal symptoms, PLK DS
      significantly suppressed sneezing, nasal discharge, and nasal obstruction. The
      effect of PLK DS on nasal obstruction was most prominent, with significant
      improvement relative to placebo beginning 60 minutes after the start of exposure.
      No serious adverse events were  reported during the study. In this study, PLK DS
      is effective and safe for treatment in children with SAR.

PMID- 22370536
TI  - A 71-year-old man with anaphylaxis after eating grits.
AB  - The allergist is frequently called on to evaluate patients after episodes of
      anaphylaxis to determine the cause and implement preventive measures that will
      reduce the patient's risk from future episodes. The etiology of anaphylaxis can
      be the result of numerous causes that may go undiagnosed  if a thorough
      evaluation is not performed. We present a 71-year-old man with no history of food
      allergy or atopy who presented to the emergency room and then our allergy clinic
      for evaluation after suffering anaphylaxis after a meal of grits and shrimp. The
      underlying diagnosis, which was  subsequently determined, requires a high index
      of suspicion and should be included in the differential diagnosis of any patient
      presenting with unexplained anaphylaxis.

PMID- 22370537
TI  - Commentary on the recorded history of angioedema.

PMID- 22370538
TI  - Rational synthesis of 1,3-diolein by enzymatic esterification.
AB  - t-Butanol was an excellent reaction medium for enzyme-mediated esterification of
      oleic acid with glycerol for 1,3-diolein preparation which has been proved by our
      group. Herein, to achieve the rational synthesis of 1,3-diolien, response surface
      methodology was applied to examine the effects of the significant variables and
      their reciprocal effects on the product synthesis. Under the optimal conditions
      (62.4 degrees C, 0.75g Novozym 435, substrate molar ratio (oleic acid/glycerol)
      2.4 and 4.8g t-butanol), the diolein yield of 87.4% could be achieved, and the
      value of 1,3-diolien/diolein was as high as 87.8%, which were quite close to the
      predicted values. Compared with the results of our previous single factor
      experiment, although the values of diolein yield and 1,3-diolien/diolein could
      not be improved markedly, the enzyme dosage and the reaction medium were spared
      by 25% and 20%, respectively, which was a remarkable improvement of the enzymatic
      process.

PMID- 22370539
TI  - Engineering a thermostable beta-1,3-1,4-glucanase from Paecilomyces thermophila
      to improve catalytic efficiency at acidic pH.
AB  - To fulfill the need for acid-tolerant and thermostable beta-1,3-1,4-glucanases,
      an error-prone PCR and DNA-shuffling approach was employed to enhance the
      activity of thermostable beta-1,3-1,4-glucanases from Paecilomyces thermophila
      (PtLic16A) at acidic pH. Mutant PtLic16AM2 was selected and characterized, and
      showed optimal activity at pH 5.0, corresponding to an acidic shift of 2.0 pH
      units relative to the wild-type enzyme. Other properties of PtLic16A such as
      temperature optimum and substrate specificity that are beneficial for industrial
      applications did not change. Based on the substituted residues of PtLic16AM2,
      three site-directed mutations, D56G, D221G and C263S, were designed to study
      these residues' roles. The amino acid residues at positions 56 and 263 were found
      to be important in determining optimal pH activity. Activity of the D221G variant
      showed no significant difference from the wild-type. Thus, it appears that the
      change in optimal pH for PtLic16AM2 was mainly caused by the combination of
      substitutions D56G and C263S. This study provides a beta-1,3-1,4-glucanase
      (PtLic16AM2) with high potential for industrial applications.

PMID- 22370544
TI  - Prostate cancer: beta-Catenin:androgen receptor ratio could guide personalized
      CRPC treatment in men with bone metastases.

PMID- 22370546
TI  - BPH: predicting TWOC failure in acute urinary retention.

PMID- 22370550
TI  - Prostatitis: men with chronic prostatitis at risk for colorectal cancer?

PMID- 22370551
TI  - A questionnaire survey of critical care nurses' attitudes to delirium assessment
      before and after introduction of the CAM-ICU.
AB  - BACKGROUND: Nurses are usually the first to identify delirium in ICU patients. We
      aimed to assess the attitudes of Australian critical care nurses when we
      introduced the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
      METHODS: We surveyed all 174 nurses in our ICU using two questionnaires: first
      after a one-month period of mandated but unstructured delirium assessments, and
      then following one month of CAM-ICU assessments. We also quantified antipsychotic
      medication usage by inspecting pharmacy records. FINDINGS: The first survey
      response rate was 65/174 (37%). Most nurses (73%) thought active delirium
      assessment was important, and 93% thought their assessments were worth the time
      required. These assessments were largely unstructured, as only 20% knew a formal
      delirium test, and only 7% sometimes used one. The second survey response rate
      was 45/174 (26%). Most (89%) still thought delirium assessment was important, but
      only 75% thought the CAM-ICU worth the time required (p=0.01 compared to
      unstructured assessments). Similar proportions (75% and 73%) were confident in
      the accuracy of their assessments. Many (33%) found the CAM-ICU 'quite' or 'very'
      hard to perform, but despite this, 82% wanted to continue to use it. Free-text
      answers suggested this was because medical staff paid more attention to the CAM
      ICU. Supporting this, prescriptions of antipsychotic medications increased
      significantly in the CAM-ICU period. CONCLUSION: Critical care nurses in our
      Australian ICU who responded to our survey think delirium assessment is
      important. Although they find unstructured assessments easier to perform, they
      wanted to persist with the CAM-ICU, in part because it facilitated more
      appropriate pharmacological treatment of delirium for their patients. We
      recommend the CAM-ICU as a tool to improve communication between nurses and
      physicians in the management of delirium.

PMID- 22370552
TI  - A framework for designing and analyzing binary decision-making strategies in
      cellular systems.
AB  - Cells make many binary (all-or-nothing) decisions based on noisy signals gathered
      from their environment and processed through noisy decision-making pathways.
      Reducing the effect of noise to improve the fidelity of decision-making comes at
      the expense of increased complexity, creating a tradeoff between performance and
      metabolic cost. We present a framework based on rate distortion theory, a branch
      of information theory, to quantify this tradeoff and design binary decision
      making strategies that balance low cost and accuracy in optimal ways. With this
      framework, we show that several observed behaviors of binary decision-making
      systems, including random strategies, hysteresis, and irreversibility, are
      optimal in an information-theoretic sense for various situations. This framework
      can also be used to quantify the goals around which a decision-making system is
      optimized and to evaluate the optimality of cellular decision-making systems by a
      fundamental information-theoretic criterion. As proof of concept, we use the
      framework to quantify the goals of the externally triggered apoptosis pathway.

PMID- 22370556
TI  - Coordination bonding based pH-responsive albumin nanoparticles for anticancer
      drug delivery.
AB  - Zn-loaded bovine serum albumin nanoparticles (Zn-BSA nanoparticles) were prepared
      and used as carriers for pH-responsive anticancer drug delivery. Zinc was
      introduced into this system to increase the stability of the BSA nanoparticles
      and to load the anticancer drug based on the coordination bonding formation of Zn
      BSA and Zn-drug molecules, respectively. The cleavage of either the "Zn-BSA" or
      the "Zn-drug" coordination bonding, in response to pH, would result in the
      release of the drug under designated pH conditions. The nanoparticles were
      spherical with diameters of 50-60 nm and narrow size distribution. Mitoxantrone
      (MX) was chosen as the model drug to study the release behavior and the
      inhibitory efficacy against tumor cells. In vitro release behavior of MX loaded
      Zn-BSA nanoparticles (MX-Zn-BSA nanoparticles) showed a fine pH-responsiveness.
      The release amount at pH 5.0 was close to 80%, while the cumulative release
      amount at pH 7.4 was less than 6% within 24 h. The blank Zn-BSA nanoparticles
      were of low cytotoxicity, while a high cytotoxic activity of MX-Zn-BSA
      nanoparticles against MCF-7 cells was demonstrated by in vitro cell assays.

PMID- 22370553
TI  - The neuroprotective and lifespan-extension activities of Damnacanthus officinarum
      extracts in Caenorhabditis elegans.
AB  - AIM OF THE STUDY: This study was aimed to evaluate the neuroprotective and anti
      aging activity of extracts in Caenorhabditis elegans from the roots and leaves of
      Damnacanthus officinarum Huang to provide the pharmacological basis in
      traditional medicine. MATERIALS AND METHODS: Investigations on the
      neuroprotective and lifespan activity were carried out, which were observed by
      utilizing the following models: observing the worms' chemosensory behavior test
      based on the aversion index in the assay plate, neuroprotective activity of
      nematode by evaluating the ASH neuron survival and lifespan test in C. elegans.
      RESULTS: It has been shown that the ethanol, n-butanol and aqueous extracts in
      the roots possessed significantly neuroprotective effect both in chemosensory
      behavior test and ASH neuron survival model. The same extracts in the leaves
      showed similar activities in two models, but have less potency revealing by the
      data. Four candidate extracts, possessing excellent neuroprotective activity,
      extend lifespan in C. elegans. The n-butanol extracts in the root part showed
      best efficacy among them. CONCLUSION: The results show the n-butanol and aqueous
      extracts are the major pharmacological plant extracts. Moreover, the
      neuroprotective and lifespan-extension activity effects of root extracts are
      superior to leave extracts, supporting the traditional application of above
      ground parts of DOH in treating various diseases associated with brain disorders
      and anti-aging.

PMID- 22370557
TI  - The distal C-terminal region of the KcsA potassium channel is a pH-dependent
      tetramerization domain.
AB  - The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric
      potassium channel, is a 40-residue-long segment that natively adopts a helical
      bundle conformation with 4-fold symmetry. A hallmark of KcsA behavior is pH
      induced conformational change, which leads to the opening of the channel at
      acidic pH. Previous studies have reached conflicting conclusions as to the role
      of the CTD in this transition. Here, we investigate the involvement of this
      domain in pH-mediated channel opening by NMR using a soluble peptide
      corresponding to residues 128-160 of the CTD (CTD34). At neutral pH, CTD34
      exhibits concentration-dependent spectral changes consistent with oligomer
      formation. We prove this slowly tumbling species to be a tetramer with a
      dissociation constant of (2.0+/-0.5)*10(-)(11) M(3) by NMR and sedimentation
      equilibrium experiments. Whereas monomeric CTD34 is only mildly helical,
      secondary chemical shifts prove that the tetrameric species adopts a tight native
      like helical bundle conformation. The tetrameric species undergoes pH-dependent
      dissociation, and CTD34 is fully monomeric below pH 5.0. The structural basis for
      this phenomenon is the destabilization of the tetrameric CTD34 by protonation of
      residue H145 in the monomeric form of the peptide. We conclude that (i) the CTD34
      peptide is independently capable of forming a tetrameric helical bundle, and (ii)
      this structurally significant conformational shift is modulated by the effects of
      solution pH on residue H145. Therefore, the involvement of this domain in the pH
      gating of the channel is strongly suggested.

PMID- 22370558
TI  - Mutations in Drosophila myosin rod cause defects in myofibril assembly.
AB  - The roles of myosin during muscle contraction are well studied, but how different
      domains of this protein are involved in myofibril assembly in vivo is far less
      understood. The indirect flight muscles (IFMs) of Drosophila melanogaster provide
      a good model for understanding muscle development and function in vivo. We show
      that two missense mutations in the rod region of the myosin heavy-chain gene,
      Mhc, give rise to IFM defects and abnormal myofibrils. These defects likely
      result from thick filament abnormalities that manifest during early sarcomere
      development or later by hypercontraction. The thick filament defects are
      accompanied by marked reduction in accumulation of flightin, a myosin binding
      protein, and its phosphorylated forms, which are required to stabilise thick
      filaments. We investigated with purified rod fragments whether the mutations
      affect the coiled-coil structure, rod aggregate size or rod stability. No
      significant changes in these parameters were detected, except for rod
      thermodynamic stability in one mutation. Molecular dynamics simulations suggest
      that these mutations may produce localised rod instabilities. We conclude that
      the aberrant myofibrils are a result of thick filament defects, but that these in
      vivo effects cannot be detected in vitro using the biophysical techniques
      employed. The in vivo investigation of these mutant phenotypes in IFM development
      and function provides a useful platform for studying myosin rod and thick
      filament formation generically, with application to the aetiology of human myosin
      rod myopathies.

PMID- 22370559
TI  - An equilibrium model for linear and closed-loop amyloid fibril formation.
AB  - Amyloid fibrils and their soluble oligomeric intermediates are implicated in
      several age-related diseases including Alzheimer's and Parkinson's diseases. The
      distribution of oligomers and fibrils is related to toxicity and is dependent on
      the pathways for fibril assembly, generally considered to occur via a slow
      nucleation step that precedes fibril elongation. Human apolipoprotein (apo) C-II
      forms amyloid fibrils via a reversible self-assembly process accompanied by
      closed-loop formation and fibril breaking and joining. Our fluorescence quenching
      and sedimentation velocity experiments with Alexa488-labeled apoC-II indicated a
      time-dependent subunit interchange for both linear and closed-loop fibrils, while
      dilution experiments using mature fibrils indicated a shift to smaller size
      distributions consistent with a reversible assembly pathway. To account for this
      behavior, we developed an equilibrium self-association model that describes the
      final size distributions of apoC-II fibrils formed at different starting
      concentrations. The model proposes a reversible isomerization of apoC-II monomer
      to form an active conformer that self-assembles into fibrils via an isodesmic
      self-association pathway coupled to fibril length-dependent closed-loop
      formation. The model adequately described fibril size distributions and the
      proportion of closed loops as a function of total apoC-II concentration over the
      concentration range 0.1-0.5 mg/ml. Extension of the model to include the rates of
      isomerization, self-association and fibril breaking and joining provided
      satisfactory global fits to kinetic data on fibril formation and changes in
      average fibril size at different apoC-II starting concentrations. The model
      provides a simple thermodynamic description of the processes governing the size
      distribution of apoC-II fibrils at equilibrium and the formation of discrete
      oligomeric intermediates.

PMID- 22370560
TI  - A unique FGF23 with the ability to activate FGFR signaling through both
      alphaKlotho and betaKlotho.
AB  - Three fibroblast growth factor (FGF) molecules, FGF19, FGF21, and FGF23, form a
      unique subfamily that functions as endocrine hormones. FGF19 and FGF21 can
      regulate glucose, lipid, and energy metabolism, while FGF23 regulates phosphate
      homeostasis. The FGF receptors and co-receptors for these three FGF molecules
      have been identified, and domains important for receptor interaction and
      specificity determination are beginning to be elucidated. However, a number of
      questions remain unanswered, such as the identification of fibroblast growth
      factor receptor responsible for glucose regulation. Here, we have generated a
      variant of FGF23: FGF23-21c, where the C-terminal domain of FGF23 was replaced
      with the corresponding regions from FGF21. FGF23-21c showed a number of
      interesting and unexpected properties in vitro. In contrast to wild-type FGF23,
      FGF23-21c gained the ability to activate FGFR1c and FGFR2c in the presence of
      betaKlotho and was able to stimulate glucose uptake into adipocytes in vitro and
      lower glucose levels in ob/ob diabetic mice model to similar extent as FGF21 in
      vivo. These results suggest that betaKlotho/FGFR1c or FGFR2c receptor complexes
      are sufficient for glucose regulation. Interestingly, without the FGF23 C
      terminal domain, FGF23-21c was still able to activate fibroblast growth factor
      receptors in the presence of alphaKlotho. This suggests not only that sequences
      outside of the C-terminal region may also contribute to the interaction with co
      receptors but also that FGF23-21c may be able to regulate both glucose and
      phosphate metabolisms. This raises an interesting concept of designing an FGF
      molecule that may be able to address multiple diseases simultaneously. Further
      understanding of FGF/receptor interactions may allow the development of exciting
      opportunities for novel therapeutic discovery.

PMID- 22370562
TI  - Dynamics of transcription of closely spaced promoters in Escherichia coli, one
      event at a time.
AB  - Many pairs of genes in Escherichia coli are driven by closely spaced promoters.
      We study the dynamics of expression of such pairs of genes driven by a model at
      the molecule and nucleotide level with delayed stochastic dynamics as a function
      of the binding affinity of the RNA polymerase to the promoter region, of the
      geometry of the promoter, of the distance between transcription start sites
      (TSSs) and of the repression mechanism. We find that the rate limiting steps of
      transcription at the TSS, the closed and open complex formations, strongly affect
      the kinetics of RNA production for all promoter configurations. Beyond a certain
      rate of transcription initiation events, we find that the interference between
      polymerases correlates the dynamics of production of the two RNA molecules from
      the two TSS and affects the distribution of intervals between consecutive
      productions of RNA molecules. The degree of correlation depends on the geometry,
      the distance between TSSs and repressors. Small changes in the distance between
      TSSs can cause abrupt changes in behavior patterns, suggesting that the sequence
      between adjacent promoters may be subject to strong selective pressure. The
      results provide better understanding on the sequence level mechanisms of
      transcription regulation in bacteria and may aid in the genetic engineering of
      artificial circuits based on closely spaced promoters.

PMID- 22370561
TI  - Mapping the transition state for DNA bending by IHF.
AB  - How DNA-bending proteins recognize their specific sites on DNA remains elusive,
      particularly for proteins that use indirect readout, which relies on sequence
      dependent variations in DNA flexibility/bendability. The question remains as to
      whether the protein bends the DNA (protein-induced bending) or, alternatively,
      "prebent" DNA conformations are thermally accessible, which the protein captures
      to form the specific complex (conformational capture). To distinguish between
      these mechanisms requires characterization of reaction intermediates and, in
      particular, snapshots of the transition state along the recognition pathway. We
      present such a snapshot, from measurements of DNA bending dynamics in complex
      with Escherichia coli integration host factor (IHF), an architectural protein
      that bends specific sites on lambda-DNA in a U-turn by creating two sharp kinks
      in DNA. Fluorescence resonance energy transfer measurements in response to laser
      temperature-jump perturbation monitor DNA bending. We find that nicks or
      mismatches that enhance DNA flexibility at the site of the kinks show 3- to 4
      fold increase in DNA bending rates that reflect a 4- to 11-fold increase in
      binding affinities, while sequence modifications away from the kink sites, as
      well as mutations in IHF designed to destabilize the complex, have negligible
      effect on DNA bending rates despite >250-fold decrease in binding affinities.
      These results support the scenario that the bottleneck in the recognition step
      for IHF is spontaneous kinking of cognate DNA to adopt a partially prebent
      conformation and point to conformational capture as the underlying mechanism of
      initial recognition, with additional protein-induced bending occurring after the
      transition state.

PMID- 22370563
TI  - Accurate prediction of rate constants of Diels-Alder reactions and application to
      design of Diels-Alder ligation.
AB  - Bioorthogonal reactions are useful tools to gain insights into the structure,
      dynamics, and function of biomolecules in the field of chemical biology.
      Recently, the Diels-Alder reaction has become a promising and attractive
      procedure for ligation in bioorthogonal chemistry because of its higher rate and
      selectivity in water. However, a drawback of the previous Diels-Alder ligation is
      that the widely used maleimide moiety as a typical Michael acceptor can readily
      undergo Michael addition with nucleophiles in living systems. Thus, it is
      important to develop a nucleophile-tolerant Diels-Alder system in order to extend
      the scope of the application of Diels-Alder ligation. To solve this problem, we
      found that the theoretical protocol M06-2X/6-31+G(d)//B3LYP/6-31G(d) can
      accurately predict the activation free energies of Diels-Alder reactions with a
      precision of 1.4 kcal mol(-1) by benchmarking the calculations against the 72
      available experimental data. Subsequently, the electronic effect and ring-strain
      effect on the Diels-Alder reaction were studied to guide the design of the new
      dienophiles. The criteria of the design is that the designed Diels-Alder reaction
      should have a lower barrier than the Michael addition, while at the same time it
      should show a similar (or even higher) reactivity as compared to the maleimide
      involving Diels-Alder ligation. Among the designed dienophiles, three substituted
      cyclopropenes (i.e. 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2
      bis(hydroxylmethyl)-3-carboxylcyclopropenes) meet our requirements. These
      substituted cyclopropene analogs could be synthesized and they are
      thermodynamically stable. As a result, we propose that 1,2-bis(trifluoromethyl)-,
      1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes may
      be potential candidates for efficient and selective Diels-Alder ligation in
      living systems.

PMID- 22370564
TI  - Effects of block copolymer self-assembly on optical anisotropy in azobenzene
      containing PS-b-PMMA films.
AB  - Polystyrene-b-polymethylmethacrylate (PS-b-PMMA) was selected as the host for 4
      (4-nitrophenylazo)aniline (Disperse Orange 3, DO3) based on a previous study of
      DO3/PMMA and DO3/PS binary blends. Selective location of DO3 into the PMMA block
      of the copolymer was expected during self-assembly of the block copolymer since a
      preferential interaction of DO3 with PMMA has been demonstrated. However, surface
      segregation of DO3 was found during the thermal annealing used to nanostructure
      the copolymer. To avoid this, a thermoplastic polymer (Azo-TP) was synthesized
      from the bulk reaction of DO3 and diglycidyl ether of bisphenol A (DGEBA). The
      choice of DGEBA as a co-reactant was an attempt to encourage the selective
      location of azo groups in the PMMA phase of PS-b-PMMA. An inspection of solutions
      of Azo-TP in PS and PMMA, corroborates the preferential affinity of Azo-TP for
      PMMA. The Azo-TP could be satisfactorily dissolved in PS-b-PMMA. We have
      investigated the growth and decay processes of the optically induced
      birefringence in films of PS-b-PMMA containing 12 wt% Azo-TP. The resulting
      materials showed a good photoinduced time response, high maximum birefringence
      and an elevated fraction of remnant anisotropy.

PMID- 22370565
TI  - An update on risk factors, prognosis and management of melanoma patients.
AB  - Cutaneous melanoma continues to be a public health problem worldwide and its
      incidence continues to increase around the globe. The recognition of melanoma
      risk factors allows for the identification of a subgroup of high-risk patients
      that will likely benefit most from approaches aimed at minimizing exposure to
      ultraviolet radiation and from surveillance strategies geared towards finding
      melanomas while thin and easily curable. Herein, we will provide an overview of
      the most pertinent, novel and newly described melanoma risk factors and melanoma
      prognostic factors. The potential benefits of skin cancer surveillance strategies
      including physician-based total body skin examination, total body photography,
      dermoscopy and patient-based self-skin examination will be examined. In addition,
      management of melanoma patients, focusing on prevention and early detection
      strategies will be discussed.

PMID- 22370566
TI  - Surgical and histologic pitfalls in the management of lentigo maligna melanoma.
AB  - Lentigo maligna melanoma (LMM) is a malignancy with increasing incidence,
      accounting for about 4% to 15% of all melanomas. Lentigo maligna (LM) is LMM in
      situ, usually presenting an irregular tan colored or brownish pigmented macular
      lesion persisting for years on chronically sun-exposed skin. Left untreated, LM
      may evolve into invasive form of LMM. Histologic evaluation of LM/LMM can be
      difficult due to widespread atypical melanocytes that are present in the area
      chronically sun damaged skin. It has been shown that chronically sun-damaged non
      lesional skin can display some atypical features even in the absence of a
      melanocytic neoplasm. It is important for dermatopathologists to be aware of
      these findings so that such features are interpreted appropriately when making a
      histological assessment that may ultimately influence therapy and outcome. LMM is
      characterized by significant subclinical lesion extension which makes the
      treatment another challenge. Nowadays, a variety of therapeutic options are
      available in the treatment of LMM. Surgery remains the mainstay of LMM therapy,
      however the treatment of LM remains controversial subject in the literature. Non
      surgical treatment modalities for LM include: destructive procedures such
      radiotherapy, cryotherapy, curettage, laser, electro-destruction and
      immunotherapy with the topical application of 5% imiquimod cream. These treatment
      options should be considered for a subset of patients with LM, especially in
      elderly patients with extensive or unresectable disease in difficult areas on the
      face or, as a second-line therapy if surgery is contraindicated. Surgical options
      include simple excision and margin-control techniques such as staged excision and
      Mohs micrographic surgery.In this article, authors are reviewing the latest
      diagnostic and therapeutic advances in the management of LMM.

PMID- 22370567
TI  - Soft tissue filler and botulinum toxin treatment techniques.
AB  - A variety of non-invasive techniques have been utilized for the enhancement of
      cutaneous changes seen with photoaging. Such methods include chemical peels,
      microdermabrasion, ablative and nonablative lasers, and various rejuvenating
      light sources. However, the most widely used minimally invasive cosmetic
      procedures for the correction of undesired rhytides and enhance facial features
      through contouring and volumization are injections with botulinum toxin and soft
      tissue fillers. Their extensive long term safety and relative ease of procedural
      techniques have led to high satisfaction levels worldwide. Nonetheless, proper
      training of the fundamentals in injection technique, the choice of the
      appropriate candidate, and knowledge of potential adverse events are imperative
      to ensure an excellent and safe outcome.

PMID- 22370568
TI  - Cosmetic applications of sclerotherapy.
AB  - The aim of this study was to broaden practitioner perspectives regarding the
      scope, safety, and efficacy of sclerotherapy for cosmetically unattractive veins
      and other conditions involving a variety of anatomical sites. The author wrote a
      review of results obtained following cosmetic sclerotherapy for both veins and in
      other applications is presented. This study involves hundreds of patients treated
      in a private phlebology practice spanning 33 years along with a brief review of
      pertinent literature. Since treatment of dilated veins involving the dorsa of the
      hands and face are rarely discussed, and widely performed, their treatment will
      be emphasized. The largely historical usefulness of sclerotherapy for other
      applications is also reviewed. As with lower extremity veins there was a great
      deal of both regional and patient-to-patient variability in terms of sensitivity
      to sclerosants and response to treatment. However, sclerotherapy carried out for
      cosmetic purposes has routinely produced satisfactory results for various
      applications and in a multiplicity of locations. Potentially serious
      complications and treatment failures were rare in properly selected patients.
      Patient satisfaction with a few exceptions was uniformly high. The addition of
      cosmetic sclerotherapy to an established phlebology practice can be a rewarding
      and highly satisfactory application of this versatile technique. Both treatment
      site, lesion type and the cosmetic nature of this therapy affects every aspect of
      treatment; legal, ethical, and procedural. Experience suggests that each area and
      type of lesion treated exhibits predictable patterns of response and risks. Vein
      treatment outcomes varying with anatomical site may reflect: 1) evolutionarily
      adaptive processes which have produced veins specialized for specific
      environments; 2) differences in patterns of cytokine recruitment and apoptotic
      processes. It should also be noted that potential complications reflect area
      specific patterns of venous anastomoses, nerves, vital structures, and the
      complexities of arterial architecture.

PMID- 22370569
TI  - New insights about delayed allergic hypersensitivity to corticosteroids.
AB  - Corticosteroids are among the most commonly used drugs, both topically and
      systemically. Although unexpected and paradoxical, allergic hypersensitivity to
      corticosteroids is a common finding, delayed-type reactions being much more
      frequently encountered than the immediate-type ones. With regard to cross
      reactions between corticosteroids, based on patch-test results and molecular
      modelling, we were recently able to simplify the previous classification into 3
      different groups, i.e., Group 1: the non-methylated, most often non-halogenated
      molecules (Group A, D2 and budesonide), which produce most of the allergic
      reactions; Group 2: the halogenated molecules with a C16/C17 cis ketal/diol
      structure (acetonide Group B); and Group 3: the halogenated and C16-methylated
      molecules (Group C and D1) that only rarely produce allergy.

PMID- 22370571
TI  - Dermatology Life Quality Index score in vitiligo patients: a pilot study among
      young Italian males.
AB  - AIM: A negative impact on vitiligo patients in terms of quality of life (QoL) has
      been suggested. The aim of this report was to study the QoL in a sample of
      Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI)
      questionnaire. METHODS: A sample of forty seven vitiligo subjects, identified
      among 34,740 potential conscripts resident in southern Italy underwent the
      Italian version of the DLQI questionnaire. RESULTS: The median total DLQI score
      was 1 (IQR: 2; mean: 1.82). In univariate analysis, DLQI total score was
      significantly influenced by the clinical course of vitiligo, disease extension
      over the body, and location on face and/or hands. Multivariate analysis using
      logistic stepwise regression showed that only the localization on the hands and
      on the face influenced significantly the mean DLQI. CONCLUSION: Our study
      conducted on a random sample of individuals affected by vitiligo selected from
      the general young male population in Italy, does not document a large impact of
      vitiligo on QoL. However, variations exist and the location of lesions on the
      face and/or hands may impact on QoL. Population-based studies are not affected by
      selection biases connected with seeking medical care and should be more widely
      performed.

PMID- 22370570
TI  - Atopic dermatitis (AD) management in an Italian pediatric clinic.
AB  - AIM: Atopic dermatitis (AD) is a common, chronic relapsing inflammatory skin
      disease characterized by dry skin and variable pruritus sometimes associated with
      allergic disease in other organs as asthma and rhinoconjunctivitis. AD affects
      deeply the Quality of Life, thus can be extremely disabling and may cause
      psychological problems for both affected children and their families. METHODS: In
      order to investigate the estimated prevalence of the disease and the beliefs of
      the Italian pediatricians, a group of 437 Italian family pediatricians covering a
      population of almost 380000 children participated in a study based on a
      questionnaire of 38 items. RESULTS: According to answers of the participants, the
      incidence of AD has been estimated around 10% of the population and food allergy
      is believed to be the trigger of the acute phase of the disease in infants. As a
      second opinion, dermatologists are consulted more frequently than allergologists.
      CONCLUSION: The use of emollients is advised in general whilst topical
      corticosteroids treatment is prescribed only in selected cases; more than 50% of
      pediatricians do not prescribe topical calcineurin inhibitors.

PMID- 22370572
TI  - Evaluation of incidental thyroid nodules in patients with primary melanoma.
AB  - AIM: Literature data have suggested an increase of incidental thyroid nodules in
      patients with malignancies, including melanoma. METHODS: The ultrasound findings
      of 168 consecutive melanoma patients were revisited in order to evaluate the
      presence of incidental thyroid nodules and the results were compared with
      clinical features, Breslow thickness and the rate of malignancy of incidental
      thyroid nodules. RESULTS: We observed that: 1) incidental thyroid nodules are
      more frequent in patients affected by melanoma (60.6%) than in the healthy
      population; 2) no statistically significant difference were found in thyroid
      involvement on the basis of gender and age; 3) incidental thyroid nodules
      frequency is increased in patients with thinner melanoma and this increase is
      more evident if we consider melanoma in situ and female patients; 4) it was not
      detected malignant incidental thyroid nodules. CONCLUSION: The data revealed a
      high frequency of incidental thyroid nodules in patients with melanoma,
      suggesting that it is necessary to study this association in a larger group of
      patients, also including age/gender matched controls.

PMID- 22370573
TI  - Methyl-aminolevulinate photodynamic therapy for the treatment of actinic
      cheilitis: a retrospective evaluation of 29 patients.
AB  - AIM: Multiple treatment modalities have been proposed for actinic cheilitis (AC),
      and topical photodynamic therapy (PDT) has recently been included among these
      modalities. We report our experience with PDT using methyl-aminolevulinate (MAL)
      in AC. METHODS: We performed a retrospective analysis of 29 patients who had
      undergone MAL-PDT for treatment of AC: 4 patients received one single session and
      25 patients two consecutive weekly sessions. RESULTS: At 3 months, 21 patients
      (72%) obtained a complete clinical response, which was sustained over a follow-up
      period of 6-36 months (mean, 20 months) in 20 patients. Cosmetic outcome was
      generally rated as good or very good. Transient local adverse events related to
      the procedure were common and mild to moderate in the majority of cases.
      CONCLUSION: Our preliminary experience suggests that MAL-PDT may be considered a
      valid modality for the treatment of AC, although long-term follow-up studies in
      large patient series are required to obtain precise data about clinical and
      histological recurrences.

PMID- 22370574
TI  - Add-on diagnostic tool for allergic contact dermatitis: the strip patch test.
AB  - The "conventional" patch test (PT) is considered to be the "gold standard" in
      diagnosing allergic contact dermatitis. However, the method of patch testing has
      repeatedly been criticized for its limited diagnostic accuracy and it is
      therefore by no means uniformly accepted as a reliable test method. Basic idea of
      the "strip" patch test (SPT), a modification by repeated tape stripping prior to
      patch testing, is to increase the quantity of allergen reaching the deeper
      epidermal cell layers and, thus, to increase the test sensitivity. The SPT
      according to our proposed standardized protocol is promising to improve diagnosis
      of allergic contact dermatitis which is demonstrated exemplary in the field of
      occupational contact dermatitis.

PMID- 22370575
TI  - Human phthiriasis. Can dermoscopy really help dermatologists? Entodermoscopy: a
      new dermatological discipline on the edge of entomology.
AB  - The diagnosis of human phtiriasis (often referred to as the "crab" or the "pubic
      louse") can be more difficult than other types of pediculosis (Pediculus corporis
      and Pediculus capitis) because this insect has a smaller body of 1.2 x 0.8 mm,
      may be lighter in color, not as mobile and therefore harder to see to the naked
      eye. Can dermoscopy aid to perform a better analysis of the skin? The clinical
      experience developed in two patients gives an affirmative answer, moreover adding
      useful information of insect and its eggs already known to entomologists but
      never used in dermatological diagnosis. The identification in vivo can
      distinguish Phthirus pubis from other skin signs while the conical shape of the
      operculum and the wide fixing sleeve of egg to hair, tells what species of louse
      is infesting, even if the insect is unavailable or nits are elsewhere from the
      pubic area. Entodermoscopy, provided that dermatologists have some knowledge of
      entomology, therefore promises advantages over standard microscopic examination.

PMID- 22370576
TI  - Papular-purpuric "gloves and socks" syndrome.
AB  - Papular-purpuric "gloves and socks" syndrome (PPGSS), is an acute dermatosis
      characterized by a papular-purpuric edematous rash in a distinct ''gloves and
      socks'' distribution often accompanied by fever, asthenia and lymphadenophaties.
      It is mainly caused by parvovirus B19 (B19V) but other viruses and drugs such as
      trimethoprim/sulfametaxol or chemotherapics may be involved. We describe a case
      of PPGSS with a serologically proven B19V infection in a 42-year-old Italian
      kindergarten teacher suffering from acute bacterial pharyngitis Immunoglobulin M
      by enzyme-linked immunosorbent assay (ELISA) to parvovirus B19 were positive.
      Histological examination showed dermal-ipodermal inflammation with evidence of
      leukocytoclastic vasculitis principally interesting the small venules The
      cutaneous rash resolved after 2 weeks. We reported our case to support that PPGSS
      is an immunomediated disease and that B19V morbidity varies with the immunologic
      and hematologic status of the host. In addition, a patient with PPGSS might be
      infectious at the moment of diagnosis, with significant implication for
      susceptible contacts.

PMID- 22370577
TI  - Localized reactive erythemas of different types in a family.
AB  - "Reactive erythemas" is an umbrella term grouping several different conditions,
      all of which have in common the fact of being stereotypical inflammatory clinical
      patterns of the skin in response to disparate infectious, immune, or toxic
      factors. Typically, such eruptions are symmetrical or disseminated. The here
      reported cases are different. An elderly man underwent recurrent infections of an
      epidermoid cyst, accompanied by a typical erythema annulare centrifugum near the
      infectious focus. His grandson, aged ten months, presented with an infectious
      conjunctivitis, during the resolution of which two small annular lesions,
      compatible with annular erythema of infancy, appeared on the face. A man aged 42,
      respectively son and father of the two former patients, presented with an
      erythema multiforme target lesion proximally to an infected wound. There were no
      detectable predisposing factors in all cases. Familial cases of reactive
      erythemas have been reported. However, such limited distributions have not yet
      been described.

PMID- 22370578
TI  - Sweet's syndrome with panniculitis.

PMID- 22370579
TI  - Erythema annulare centrifugum: a "deep type" figurate eruption.

PMID- 22370580
TI  - Pilomatrixoma, a misdiagnosed lesion: two pediatric case reports.

PMID- 22370581
TI  - Talon Noir: utility of dermoscopy for differential diagnosis with respect to
      other acral skin growths.

PMID- 22370582
TI  - Photoexcited structural dynamics of an azobenzene analog 4-nitro-4'-dimethylamino
      azobenzene from femtosecond stimulated Raman.
AB  - Azobenzenes are used in many applications because of their robust and reversible
      light induced trans?cis isomerization about the N=N bond, but the mechanism of
      this ultrafast reaction has not been conclusively defined. Addressing this
      problem we have used Femtosecond Stimulated Raman Spectroscopy (FSRS) to
      determine the structural transients in the trans->cis photoisomerization of the
      azobenzene derivative, 4-nitro-4'-dimethylamino-azobenzene (NDAB). Key marker
      modes, such as the 1570/1590 cm(-1) NO(2) stretch and the 1630 cm(-1) C-N(Me)(2)
      stretch, enable the separation and analysis of distinct trans and cis
      photoproduct dynamics revealing the 400 fs Frank-Condon relaxation, the 800 fs
      timescale of the cis product formation and the 2 ps emergence and 8 ps relaxation
      of the unsuccessful ground state trans species. Based on these observations, we
      propose a reaction mechanism, including initial dilation of the CNN bend later
      joined by quick movement along the CCNN, CNNC and NNCC torsional coordinates that
      constitutes a mixed inversion-rotation mechanism.

PMID- 22370583
TI  - Drug targeting to the diseased liver.
AB  - Many serious liver diseases affecting millions of people world-wide cannot be
      treated despite many efforts which warrants a search for new therapeutic
      strategies. Potent drugs may not be effective enough in vivo or exhibit adverse
      effects and enhanced delivery into the target cells may improve this
      significantly. We aim to summarize the available options for drug delivery to the
      different intrahepatic cell-types. The most relevant target cells are identified
      for each liver disease and the strategies for drug delivery to these cells are
      subsequently reviewed. The review describes the use of proteins, viruses,
      polymers and liposomes for therapeutic purposes in various liver diseases. It is
      shown that to date, all resident intrahepatic cells can be reached with several
      different drug carriers. Much progress has been made in recent years to deliver
      small drug molecules, proteins and nucleic acids specifically to the key
      pathogenic cells in vivo. The knowledge of drug targeting gained in the past
      decades, combined with a proper preclinical evaluation, may bring new
      therapeutics to the clinic in the near future.

PMID- 22370584
TI  - Development of a molecularly imprinted polymer-matrix solid-phase dispersion
      method for selective determination of beta-estradiol as anabolic growth promoter
      in goat milk.
AB  - A simple, fast, and sensitive method for determination of 17 beta-estradiol (E2)
      in goat milk samples has been developed by combining selective molecularly
      imprinted matrix solid-phase dispersion (MIP-MSPD) and liquid chromatography with
      diode-array detection (DAD). The molecularly imprinted polymer was synthesized by
      use of 17beta-estradiol as template molecule, methacrylic acid as functional
      monomer, ethylene glycol dimethacrylate as crosslinker monomer,
      azobisisobutyronitrile as initiator, and acetonitrile as porogen, and was used as
      selective solid support for matrix solid-phase dispersion. The selected
      dispersant had high affinity for E2 in the goat milk matrix and the extract
      obtained was sufficiently clean for direct injection for HPLC analysis without
      any interferences from the matrix. The proposed MIP-MSPD method was validated for
      linearity, precision, accuracy, decision limit (CCalpha) and detection capability
      (CCbeta), in accordance with European Commission Decision 2002/657/EC criteria.
      Linearity ranged from 0.3-10 MUg g(-1) (correlation coefficient r(2) > 0.999).
      Mean recovery of E2 from goat milk samples at different spiked levels was between
      89.5 and 92.2%, with RSD values within 1.3-2%. CCalpha and CCbeta values were
      0.36 and 0.39 MUg g(-1), respectively. The developed MIP-MSPD method was
      successfully applied to direct determination of E2 in goat milk samples.

PMID- 22370585
TI  - Use of NMR metabolomic plasma profiling methodologies to identify illicit growth
      promoting administrations.
AB  - Detection of growth-promoter use in animal production systems still proves to be
      an analytical challenge despite years of activity in the field. This study
      reports on the capability of NMR metabolomic profiling techniques to discriminate
      between plasma samples obtained from cattle treated with different groups of
      growth-promoting hormones (dexamethasone, prednisolone, oestradiol) based on
      recorded metabolite profiles. Two methods of NMR analysis were investigated-a
      Carr-Purcell-Meiboom-Gill (CPMG)-pulse sequence technique and a conventional (1)H
      NMR method using pre-extracted plasma. Using the CPMG method, 17 distinct
      metabolites could be identified from the spectra. (1)H NMR analysis of extracted
      plasma facilitated identification of 23 metabolites-six more than the alternative
      method and all within the aromatic region. Multivariate statistical analysis of
      acquired data from both forms of NMR analysis separated the plasma metabolite
      profiles into distinct sample cluster sets representative of the different animal
      study groups. Samples from both sets of corticosteroid-treated animals
      dexamethasone and prednisolone-were found to be clustered relatively closely and
      had similar alterations to identified metabolite panels. Distinctive metabolite
      profiles, different from those observed within plasma from corticosteroid-treated
      animal plasma, were observed in oestradiol-treated animals and samples from these
      animals formed a cluster spatially isolated from control animal plasma samples.
      These findings suggest the potential use of NMR methodologies of plasma
      metabolite analysis as a high-throughput screening technique to aid detection of
      growth promoter use.

PMID- 22370586
TI  - Determination of azide in gastric fluid and urine by flow-injection electrospray
      ionization tandem mass spectrometry.
AB  - A rapid method was developed to identify and quantify the azide ion (N(3)(-)) in
      gastric fluid and urine. N(3)(-) in diluted biological fluids was reacted with
      NaAuCl(4) to produce Au(N(3))(2)(-), which was extracted with octanol. Five
      microliters of the extract were flow-injected into an electrospray ionization
      tandem mass spectrometric instrument. Quantification of N(3)(-) was performed by
      selected reaction monitoring of the product ion Au(N)(N(3))(-) at m/z 253, which
      was derived from the precursor ion Au(N(3))(2)(-) at m/z 281, using 50 MUL of
      aqueous solution within 10 min. This method was found to be linear up to 10(-5)
      M, to have a limit of quantification of 10(-7) M, a limit of detection of 3.0 *
      10(-8) M, and a coefficient of variation of ?10% at 10(-7) M. In the case of
      urine, 50 MUL of urine were spiked with N(3)(-), this was diluted 10-fold and
      passed through 1 mL of a resin, and finally diluted to 100-fold of the original.
      This method was linear up to 10(-3) M, had a limit of quantification of 10(-5) M,
      a limit of detection of 3.0 * 10(-6) M, and coefficient of variation of ?8.8% for
      an original urine concentration of 10(-5) M. The practical applicability of this
      method was checked by diluting 1 MUL of a suspected suicide victim's gastric
      fluid 20,000-fold and 1 MUL of the victim's urine 5,000-fold and then measuring
      the N(3)(-) levels. These levels were found to be (7.5 +/- 1.0) * 10(-2) M and
      (3.2 +/- 0.4) * 10(-3) M, respectively.

PMID- 22370587
TI  - Time course of expiratory propofol after bolus injection as measured by ion
      molecule reaction mass spectrometry.
AB  - Propofol in exhaled breath can be detected and monitored in real time by ion
      molecule reaction mass spectrometry (IMR-MS). In addition, propofol concentration
      in exhaled breath is tightly correlated with propofol concentration in plasma.
      Therefore, real-time monitoring of expiratory propofol could be useful for
      titrating intravenous anesthesia, but only if concentration changes in plasma can
      be determined in exhaled breath without significant delay. To evaluate the
      utility of IMR-MS during non-steady-state conditions, we measured the time course
      of both expiratory propofol concentration and the processed
      electroencephalography (EEG) as a surrogate outcome for propofol effect after an
      IV bolus induction of propofol. Twenty-one patients scheduled for routine surgery
      were observed after a bolus of 2.5 mg kg(-1) propofol for induction of
      anesthesia. Expiratory propofol was measured using IMR-MS and the cerebral
      propofol effect was estimated using the bispectral index (BIS). Primary endpoints
      were time to detection of expiratory propofol and time to onset of propofol's
      effect on BIS, and the secondary endpoint was time to peak effect (highest
      expiratory propofol or lowest BIS). Expiratory propofol and changes in BIS were
      first detected at 43 +/- 21 and 49 +/- 11 s after bolus injection, respectively
      (P = 0.29). Peak propofol concentrations (9.2 +/- 2.4 parts-per-billion) and
      lowest BIS values (23 +/- 4) were reached after 208 +/- 57 and 219 +/- 62 s,
      respectively (P = 0.57). Expiratory propofol concentrations measured by IMR-MS
      have similar times to detection and peak concentrations compared with propofol
      effect as measured by the processed EEG (BIS). This suggests that expiratory
      propofol concentrations may be useful for titrating intravenous anesthesia.

PMID- 22370588
TI  - Electrochemistry-mass spectrometry: an emerging hyphenated technique for
      bioanalysis.

PMID- 22370589
TI  - In-line solid-phase extraction-capillary electrophoresis coupled with mass
      spectrometry for determination of drugs of abuse in human urine.
AB  - In-line solid-phase extraction-capillary electrophoresis coupled with mass
      spectrometric detection (SPE-CE-MS) has been used for determination of 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), codeine (COD),
      hydrocodeine (HCOD), and 6-acetylmorphine (6AM) in urine. The preconcentration
      system consists of a small capillary filled with Oasis HLB sorbent and inserted
      into the inlet section of the electrophoresis capillary. The SPE-CE-MS
      experimental conditions were optimized as follows: the sample (adjusted to pH
      6.0) was loaded at 930 mbar for 60 min, elution was performed with methanol at 50
      mbar for 35 s, 60 mmol L(-1) ammonium acetate at pH 3.8 was used as running
      buffer, the separation voltage was 30 kV, and the sheath liquid at a flow rate of
      5.0 MUL min(-1) was isopropanol-water 50:50 (v/v) containing 0.5% acetic acid.
      Analysis of urine samples spiked with the four drugs and diluted 1:1 (v/v) was
      studied in the linear range 0.08-10 ng mL(-1). Detection limits (LODs) (S/N = 3)
      were between 0.013 and 0.210 ng mL(-1). Repeatability (expressed as relative
      standard deviation) was below 7.2%. The method developed enables simple and
      effective determination of these drugs of abuse in urine samples at the levels
      encountered in toxicology and doping.

PMID- 22370590
TI  - Obese women's barriers to mammography and pap smear: the possible role of
      personality.
AB  - Obese women are at increased risk of developing and dying from cancer, but are
      less likely than nonobese women to receive cancer screening examinations. Our
      qualitative study explores obese women's barriers to Pap smears and mammograms in
      greater depth than previous research. We also seek to understand why some obese
      women undergo screening whereas others do not. A purposive sample of moderately
      to severely obese women over age 40 was recruited from community-based
      organizations, health clinics, and retail establishments. Semi-structured in
      depth interviews (N = 33) informed by the Theory of Care-Seeking Behavior and
      three prior focus groups of obese women (N = 18) were recorded and transcribed.
      Qualitative analysis was iterative, using a grounded theory approach involving a
      series of immersion/crystallization cycles. Participants verified many barriers
      to cervical and breast cancer screening previously identified in the general
      population, including fear, modesty, competing demands, and low perceived risk.
      Participants also highlighted several weight-related barriers, including
      insensitive comments about weight and equipment and gowns that could not
      accommodate them. Comparison of participants who were up-to-date with both Pap
      smears and mammograms with those not up-to-date with either screening showed no
      discernable differences in these barriers, however. Instead, we found that the
      participants who followed through on their cancer screenings may share certain
      personality traits, such as conscientiousness or self-regulatory ability, that
      allow them to complete difficult or feared tasks. Our research therefore suggests
      that personality may act as an important mediator in health behavior, and should
      be taken into account in future theoretical models and health behavior
      interventions, particularly for obese women.

PMID- 22370591
TI  - Relationship between status of plasma atrial natriuretic peptide and heart rate
      variability in human subjects.
AB  - A relationship may exist between plasma atrial natriuretic peptide (P-ANP) and
      heart rate variability (HRV), which reflects the activity of the autonomic
      nervous system. We performed a survey in human subjects to examine the
      relationship between P-ANP and HRV parameters. Three ethnic groups (Han, Uygur,
      and Kazakh) provided blood and urine samples and underwent 24-h ambulatory blood
      pressure monitoring and 24-h ECG recording (24-h Holter ECG). There was a
      positive correlation between P-ANP and HF, as well as a negative correlation
      between P-ANP and the LF/HF ratio, in all subjects from the 3 ethnic groups.
      There was no association of BP with any of the blood, urinary, and HRV
      parameters. Our results suggested the possibility of a relationship between P-ANP
      and HRV, which reflects autonomic activity. These findings are consistent with
      the previous report of a close relationship between ANP and cardiac
      parasympathetic and/or sympathetic activity.

PMID- 22370592
TI  - Anti-correlation between longevity gene SirT1 and Notch signaling in ascending
      aorta biopsies from patients with bicuspid aortic valve disease.
AB  - About 1-2% of the population present with bicuspid aortic valves (BAV), a defect
      of the aortic valve resulting in the formation of two leaflets instead of three.
      This disease leads to an abnormal aorta, altered in strength and size, which in
      turn is a high risk factor for potentially lethal events such as aortic
      dissection and aneurysm formation. BAV is inheritable, with a demonstrated
      association with Notch1, a member of the Notch intercellular signaling pathway
      that is implicated in various cardiovascular disorders. Sirtuin 1 (SirT1) is a
      protein deacetylase of the sirtuin family, whose activation appears beneficial
      for cardiac diseases. A recent study has shown that SirT1 can limit Notch
      signaling in model systems of vascular growth. If a concomitant dysregulation in
      Notch and SirT1 signaling pathways can cause the phenotypic form of human BAV is
      unknown. To address this issue, we analyzed human ascending aorta biopsies from
      BAV and control patients obtained at the time of cardiac surgery. RNA and
      proteins were extracted from formalin-fixed and paraffin-embedded specimens, and
      quantitative real-time PCR and immunoblotting were used to determine the
      expression of sirtuins and members of the Notch family of proteins. We found a
      significant increase in SirT1 expression that correlates with a decreased
      expression of the Notch signaling effectors detected. We put forward the idea
      that an altered interaction between SirT1 and Notch signaling could participate
      in BAV pathogenesis and that these molecules could be used as potential clinical
      markers.

PMID- 22370593
TI  - Apical membranes prepared by peeling from whole porcine oviducts interact with
      homologous sperm.
AB  - In mammals, interaction between sperm and oviductal epithelial cells provides the
      formation of a sperm reservoir and sperm selection at the isthmus of the oviduct.
      Several in vitro methods are used to study this interaction. Apical plasma
      membranes (APM) have been prepared by peeling from culture and differentiated
      kidney cells. In this work, we modify this method, using it for the preparation
      of APM directly from the whole oviduct, proving purity of the apical plasma
      membranes obtained by western blot for proteins of known specific locations. The
      obtained APM correspond only to the most differentiated cells, exposed at the
      lumen of the organ. Also, the prepared APM are shown by biotinylation to interact
      with sperm. The binding is at the head of sperm and induces on them prolonged
      motility and tyrosine phosphorylation of proteins of masses 92, 97, 210 and 220
      kDa. The tyrosine phosphorylation of p97 has been previously described as an
      effect of the apical membrane exposed sperm binding glycoprotein (SBG), which is
      shown to be present in the preparations described here. Upon treatment with APM,
      the tyrosine phosphorylation pattern of sperm changes from heads to tail. Thus,
      we describe an easy method for APM preparation directly from organs that allows
      the study of oviductal proteins in their context and permits sperm-oviduct
      interaction studies. This method renders APM specifically from the cells located
      at the lumen of the oviduct.

PMID- 22370594
TI  - Human first-trimester chorionic villi have a myogenic potential.
AB  - First-trimester chorionic-villi-derived cells (FTCVs) are the earliest fetal
      material that can be obtained for prenatal diagnosis of fetal disorders such as
      Duchenne muscular dystrophy (DMD). DMD is a devastating X-linked disorder
      characterized by the absence of dystrophin at the sarcolemma of muscle fibers.
      Currently, a limited number of treatment options are available for DMD, although
      cell therapy is a promising treatment strategy for muscle degeneration in DMD
      patients. A novel candidate source of cells for this approach is FTCVs taken
      between the 9th and 11th weeks of gestation. FTCVs might have a higher
      undifferentiated potential than any other tissue-derived cells because they are
      the earliest fetal material. We examined the expression of mesenchymal stem cell
      and pluripotent stem cell markers in FTCVs, in addition to their myogenic
      potential. FTCVs expressed mesenchymal stem cell markers and Nanog and Sox2
      transcription factors as pluripotent stem cell markers. These cells efficiently
      differentiated into myotubes after myogenic induction, at which point Nanog and
      Sox2 were down-regulated, whereas MyoD, myogenin, desmin and dystrophin were up
      regulated. To our knowledge, this is the first demonstration that FTCVs can be
      efficiently directed to differentiate in vitro into skeletal muscle cells that
      express dystrophin as the last stage marker of myogenic differentiation. The
      myogenic potential of FTCVs reveals their promise for use in cell therapy for
      DMD, for which no effective treatment presently exists.

PMID- 22370595
TI  - Role of L1CAM for axon sprouting and branching.
AB  - The central nervous system (CNS) has been traditionally considered as an organ
      that fails to regenerate in response to injury. Indeed, the lesioned CNS faces a
      number of obstacles during regeneration, including an overall non-permissive
      environment for axonal regeneration. However, research during the last few
      decades has identified axon sprouting as an anatomical correlate for the
      regenerative capability of the CNS to establish new connections. The
      immunoglobulin superfamily member L1CAM has been shown to promote the capability
      of neurons for regenerative axon sprouting and to improve behavioral outcomes
      after CNS injury. Here, we discuss the cell-autonomous role of L1CAM for axon
      sprouting in experimental rodent injury models and highlight the molecular
      interactions of L1CAM with ankyrins, ezrin-radixin-moesin proteins and the
      Sema3A/Neuropilin ligand-receptor complex in the context of axonal branching.

PMID- 22370596
TI  - The relationship between cell proliferation and differentiation and mapping of
      putative dental pulp stem/progenitor cells during mouse molar development by
      chasing BrdU-labeling.
AB  - Human dental pulp contains adult stem cells. Our recent study demonstrated the
      localization of putative dental pulp stem/progenitor cells in the rat developing
      molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no
      available data on the localization of putative dental pulp stem/progenitor cells
      in the mouse molar. This study focuses on the mapping of putative dental pulp
      stem/progenitor cells in addition to the relationship between cell proliferation
      and differentiation in the developing molar using BrdU-labeling. Numerous
      proliferating cells appeared in the tooth germ and the most active cell
      proliferation in the mesenchymal cells occurred in the prenatal stages,
      especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue
      dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive
      odontoblasts were arranged in the cusped areas and disappeared after postnatal
      Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5
      to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant
      ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the
      mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in
      number and reached a plateau after P1W when they mainly resided in the center of
      the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs
      co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense
      LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells
      harboring in the perivascular niche surrounding the endothelium.

PMID- 22370597
TI  - Outcomes of patients with gynecologic malignancies undergoing video-assisted
      thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion.
AB  - OBJECTIVES: We evaluated the indications and outcomes of patients with known
      gynecologic malignancies that underwent video-assisted thoracoscopic surgery
      (VATS) and pleurodesis for malignant pleural effusion. METHODS: After IRB
      approval was obtained, a retrospective study of patients with gynecologic
      malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was
      performed. Abstracted data included demographics, diagnosis, disease status,
      treatment history, indication for VATS, complications, and outcomes. RESULTS:
      Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis.
      Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty
      seven percent had recurrent disease at the time of VATS and 57% were undergoing
      chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative
      VATS to improve pulmonary status. Seven patients (17%) underwent a palliative
      VATS. The median length of stay was 7 days (range 1-53). Sixty-two percent had
      gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained
      at time of surgery (range 300-4500), and the majority (88%) of patients had a
      talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days;
      6 were for complications unrelated to their VATS. One patient was readmitted with
      hospital-acquired pneumonia and died during readmission. Median time to death
      after VATS was 104 days (range 4-1062). Patients who underwent a perioperative
      VATS had the longest survival (845 days). CONCLUSION: Patients with gynecologic
      malignancies may require a VATS/pleurodesis for symptomatic pleural effusions.
      This procedure appears to be safe and effective in this patient population.

PMID- 22370598
TI  - Comprehensibility of patient consent forms for radiation therapy of cervical
      cancer.
AB  - OBJECTIVE: The construct of Health Literacy (HL) deals with patients' capacity to
      understand their health-related instructions, consent forms, and other documents.
      A significant challenge of providing healthcare to patients with low HL is the
      complex nature of the disease process, and of requisite treatments. In radiation
      oncology specifically, the delivery of ionizing radiation is difficult enough to
      describe; describing radiation toxicity in terms of the underlying physics and
      biology is daunting. A multimodal analysis of a small sample of patient consent
      forms was undertaken in order to address this issue more closely, and identify
      the extent to which such literature contributes to the challenges faced by
      patients with low HL. METHODS: Members of national cooperative group panels
      dealing with gynecologic cancer were asked to submit copies of consent forms
      provided to patients with stage II cervical cancer. Four such forms were
      submitted and reviewed by a single person with expertise in linguistics using
      standard tools. RESULTS: Three of the four consents scored within the lower
      portion of the "adequate" range. One consent was not suitable. Consent
      readability ranged from grades 12.18 to 16.13; this means that they required at
      least a high school education to interpret, and in two cases required post
      graduate coursework. CONCLUSION: There is significant room for improvement in
      consent form design and structure. When considering cultural and socioeconomic
      appropriateness of patient consent forms, input of staff with expertise in
      linguistics should be sought.

PMID- 22370599
TI  - Incidence of and risk factors for postoperative ileus in women undergoing primary
      staging and debulking for epithelial ovarian carcinoma.
AB  - OBJECTIVE: Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC)
      improves survival. The incidence of postoperative ileus (POI) in these patients
      may be underreported because of varying POI definitions and the evolving,
      increasingly complex contemporary surgical approach to EOC. We sought to
      determine the current incidence of POI and its risk factors in women undergoing
      debulking and staging for EOC. METHODS: We retrospectively identified the records
      of women who underwent primary staging and cytoreduction for EOC between 2003 and
      2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth
      status, or reinsertion of a nasogastric tube. Perioperative patient
      characteristics and process-of-care variables were analyzed. Univariate analyses
      were used to identify POI risk factors; variables with P <=.20 were included in
      multivariate analysis. RESULTS: Among 587 women identified, the overall incidence
      of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection;
      P=.002). Preoperative thrombocytosis, involvement of bowel mesentery with
      carcinoma, and perioperative red blood cell transfusion were independently
      associated with increased POI. Postoperative ibuprofen use was associated with
      decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6
      days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs
      3 days) gastrointestinal tract (P<.001 for each). CONCLUSIONS: The rate of POI is
      substantial among women undergoing staging and cytoreduction for EOC and is
      associated with increased length of stay. Modifiable risk factors may include
      transfusion and postoperative ibuprofen use. Alternative interventions to
      decrease POI are needed.

PMID- 22370600
TI  - A binary histologic grading system for ovarian serous carcinoma is an independent
      prognostic factor: a population-based study of 4317 women diagnosed in Denmark
      1978-2006.
AB  - OBJECTIVE: To evaluate the prognostic significance of histologic grade on
      survival of ovarian serous cancer in Denmark during nearly 30 years. METHODS:
      Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with
      ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and
      tumors classified as either low-grade serous carcinomas (LGSC) or high-grade
      serous carcinomas (HGSC). Tumors in which the original pathology reports were
      described as well-differentiated were classified as LGSC, and those that were
      described as moderately or poorly differentiated were classified as HGSC. We
      obtained histologic slides from the pathology departments for women with a
      diagnosis of well-differentiated serous carcinoma during 1997-2006, which were
      then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan
      Meier methods and Cox proportional hazards regression analysis with follow-up
      through June 2009. RESULTS: Women with HGSC had a significantly increased risk of
      dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for
      age and stage. Expert review of 171 women originally classified as well
      differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12%
      were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT).
      Compared with women with confirmed LGSC, women with SBT at review had a
      significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with
      HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI:
      0.7-3.4). CONCLUSIONS: A binary grading system is a significant predictor of
      survival for ovarian serous carcinoma.

PMID- 22370601
TI  - Prognostic value of elevated preoperative serum CA125 in ovarian tumors of low
      malignant potential: a multinational collaborative study (ANZGOG0801).
AB  - OBJECTIVE: Previous studies on prognostic factors in ovarian tumors of low
      malignant potential (LMP) were too small for robust conclusions. We examined the
      prognostic impact of preoperative serum CA125 >= 50 U/ml levels in patients
      diagnosed with ovarian LMP tumors in a large multinational cohort. METHODS: This
      retrospective study included 940 patients with ovarian LMP tumors diagnosed
      between 1985 and 2008 at six gynecologic cancer centers. Patients either had
      radical treatment (bilateral salpingo-oophorectomy with or without hysterectomy)
      or conservative, fertility-sparing treatment. Multivariate Cox proportional
      hazard models were used to determine independent prognostic factors for disease
      free (DFS) and overall survival (OS). Based on receiver operating characteristic
      curve (ROC), a preoperative serum CA125 level >= 50 U/ml was considered
      "elevated". RESULTS: CA125 was more often elevated in serous than in mucinous
      tumors and in advanced FIGO stages (2 to 4) compared to stage 1. DFS at 5 years
      was 89% and 95% in patients with elevated and normal CA125 levels (p<0.05).
      Similarly, the 5-year OS was 90% among patients with elevated CA125 compared to
      95% among patients with normal levels (p<0.05). For both DFS and OS elevated
      CA125 levels and advanced stages of the disease were independent prognostic
      factors. Analysis of subgroups revealed that CA125 was only prognostic in serous
      LMP tumors. CONCLUSIONS: In the context of serous ovarian LMP tumors, elevated
      preoperative serum CA125 represents a biomarker independently associated with
      impaired disease-free and overall survival. CA125 is available in most centers
      and could inform surgeons about the risk of treatment failure.

PMID- 22370602
TI  - Trends in therapy and survival of advanced stage epithelial ovarian cancer
      patients in the Netherlands.
AB  - OBJECTIVE: The aim of this study was to describe trends in survival and therapy
      in advanced stage epithelial ovarian cancer (EOC) in the Netherlands and to
      determine if changes in therapy affected survival. METHODS: All EOC patients
      diagnosed in the Netherlands during 1989-2009 were selected from the Netherlands
      Cancer Registry. Differences in treatment over time were tested by the Cochran
      Armitage trend test. Multivariable relative survival analyses were performed to
      test whether changes in treatment are associated with survival. RESULTS: 23,399
      EOC patients were diagnosed, of whom 15,892 (67.9%) in advanced stage (stage >=
      2b). In advanced stage patients, the proportion receiving (neo-)adjuvant
      chemotherapy and optimal debulking (residuals <1cm) increased over time in all
      age groups. In elderly patients (>= 75 years) a stable proportion (approximately
      28%) did not receive any treatment. Five-year relative survival in advanced stage
      patients increased from 18% in 1989-1993 to 28% in 2004-2009. In the
      multivariable model survival improved over time (relative excess risk (RER) of
      2004-2009 was 0.71, 95% CI 0.67-0.75 compared to 1989-1993). This RER attenuated
      to 0.85 (95% CI 0.80-0.90) and 0.91 (95% CI 0.83-0.99) with inclusion of
      treatment variables in the model (surgery with chemotherapy or optimal surgery
      with chemotherapy, respectively). This suggests that the improvement was mainly,
      although not entirely, caused by changes in treatment. CONCLUSION: Treatment in
      advanced stage EOC patients in the Netherlands improved over the last two
      decades; more patients received (neo)adjuvant chemotherapy and underwent optimal
      debulking surgery. Changes in treatment led to partial improvement of survival in
      EOC patients.

PMID- 22370603
TI  - Resistin expression in breast cancer tissue as a marker of prognosis and hormone
      therapy stratification.
AB  - OBJECTIVE: Adipocytokines are adipocyte-derived hormones and well documented to
      be involved in carcinogenesis. The expression of resistin, a newly discovered
      adipocytokine, in breast cancer tissues was determined and correlated with
      patient clinicopathological variables. METHODS: Resistin expression in breast
      cancer tissues and the normal adjacent breast tissues was analyzed by
      immunohistochemistry and was correlated with clinicopathological variables as
      well as recurrence rates by the chi-square test. The prognostic value of resistin
      for disease-free and overall survival was determined by Kaplan-Meier estimates,
      and the significance of differences between curves was evaluated by the log-rank
      test. RESULTS: High resistin expression was predominantly observed in breast
      cancer tissues but not the adjacent normal breast tissues. High resistin
      expression in breast cancer tissues was correlated significantly with tumor
      stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone
      therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in
      patients with high resistin expression. While high resistin expression was
      associated with poor disease-free and overall survival, Cox regression analysis
      also revealed that resistin was an independent predictor of disease-free and
      overall survival. CONCLUSIONS: High resistin expression in breast cancer tissue
      is associated with a more malignant clinicopathological status as well as poor
      patient survival. Resistin may therefore hold promise as an independent prognosis
      predictor for breast cancer, as a marker for hormone therapy stratification and
      as a potential therapeutic target.

PMID- 22370605
TI  - Beware frontotemporal dermoids - they may have intracranial extension: a case of
      a middle cranial fossa cyst.
AB  - Congenital orbitofacial dermoid cysts are epithelial lined structures of
      ectodermal origin that may be associated with sinus tracts and variable deep
      extension. Midline lesions may extend intracranially, while lateral lesions are
      thought never to do so. Consequently only midline lesions are usually imaged
      prior to surgery. We describe a lateral dermoid sinus communicating with an
      intracerebral dermoid cyst within the middle cranial fossa in a 3 year-old with
      recurrent periorbital cellulitis and intermittent discharge from a small pimple
      in the temporal region. This case demonstrates that some lateral "dermoids" need
      to be treated with more caution if there are unusual features such as dimpling,
      discharge of material or recurrent wider infection, and preoperative imaging
      should be carried out to exclude intracranial extension.

PMID- 22370604
TI  - The diagnostic accuracy of fecal calprotectin during the investigation of
      suspected pediatric inflammatory bowel disease.
AB  - OBJECTIVES: Fecal calprotectin (FC) is elevated in patients with inflammatory
      bowel disease (IBD). Studies evaluating FC during the initial investigation of
      children with suspected IBD have been limited, especially with regard to their
      small patient groups. We aimed to evaluate the diagnostic accuracy of FC in a
      large regional cohort of children undergoing full upper and lower endoscopy for
      suspected IBD, comparing FC with six common blood parameters. METHODS: Using a
      retrospective case-control design all FC measurements carried out between 2005
      and 2010 in children <18 years old were obtained. All IBD and non-IBD patients
      who had a FC measurement available before full endoscopic evaluation for
      suspected bowel inflammation were examined. FC was measured using the PhiCal
      Test. Multivariate analyzes and receiver operating characteristic curve
      generation were used to derive significance. RESULTS: A total of 190 patients (91
      IBD and 99 non-IBD controls) met the inclusion criteria. Median FC at diagnosis
      for the IBD group was 1,265 MUg/g (interquartile range (IQR) 734-2,024 MUg/g),
      compared with 65 MUg/g (IQR 20-235 MUg/g) in controls (P<0.001). FC levels did
      not vary significantly between patients with Crohn's disease, ulcerative colitis,
      and IBD unclassified and were not influenced by age or disease location. FC was
      found to be far superior to commonly utilized blood parameters such as C-reactive
      protein and white cell count (both P<0.01), with an area under the curve of 0.93
      (95% confidence interval 0.89-0.97). CONCLUSIONS: This study demonstrates that FC
      is an invaluable tool in determining those children who may require endoscopy for
      suspected IBD, and elevated values should prompt further investigation.

PMID- 22370606
TI  - Up-regulation of IL-33 expression in various types of murine cells by IL-3 and IL
      4.
AB  - The crucial roles of the novel cytokine IL-33 in allergic, inflammatory,
      infectious and autoimmune diseases are becoming characterized. However, the
      cytokines which regulate IL-33 expression and secretion are still largely
      unknown. In this study, IL-3 and IL-4 were found to up-regulate IL-33 mRNA
      expression in mouse peritoneal exudate cells by a two-color DNA microarray and
      further confirmed by real time PCR and ELISA. IL-3 and IL-4 synergistically
      promote IL-33 mRNA expression and IL-33 intracrine in the heterogeneous cell
      populations as peritoneal exudates cells, bone marrow cells and splenic cells. IL
      3 and IL-4 also induced IL-33 introcrine in the peritoneal exudate cells from the
      macrophage-deficient op/op mice, suggesting that macrophage is not the only
      target of IL-3 and IL-4 in the heterogeneous peritoneal exudate cells.
      Furthermore, IL-3 and IL-4 were verified to promote the IL-33 intracrine in the
      homogeneous cell population as fibroblasts and mast cells. These results indicate
      that up-regulation of IL-33 expression by IL-3 and IL-4 is not a feature
      particular to a specific type of cells. Up to 100 cytokines were screened, but
      none of them stimulated the secretion or release of IL-33 in the culture system.
      In summary, we confirm for the first time that IL-3 and IL-4 are critical for IL
      33 intracrine in murine cells of various types, indicating that IL-3 and IL-4 may
      play an important role in the constitutive expression of IL-33 in vivo.

PMID- 22370607
TI  - Vascular endothelial growth factor gene polymorphisms in North Indian patients
      with end stage renal disease.
AB  - CONTEXT: Vascular endothelial growth factor (VEGF) is involved in the development
      and differentiation of the vascular system. VEGF is expressed constitutively by
      epithelial cells from embryonic to adult kidneys and may play a key role in
      progression of kidney diseases. It is required for the growth and proliferation
      of glomerular and peritubular endothelial cells. In the kidney VEGF expression is
      prominently found in glomerular podocytes and in tubular epithelial cells, while
      VEGF receptors are mainly seen on preglomerular, glomerular, and peritubular
      endothelial cells. OBJECTIVES: We have investigated the role of VEGF gene
      polymorphisms (-2578C/A,-2549 18 bp I/D, -1154 G/A and +936 C/T) as a
      susceptibility marker for end stage renal disease (ESRD). PARTICIPANTS AND
      METHODS: We genotyped VEGF gene polymorphism in three hundred patients and three
      hundred and fifty ethnically matched unrelated healthy controls free from any
      renal disease. These markers were studied using ARMS-PCR and PCR-RFLP methods.
      Patients were categorized on the basis of the histo-pathological subtypes into
      chronic glomerulonephritis (CGN=109), hypertensive nephrosclerosis (HTN=106) and
      chronic interstitial nephritis (CIN=60). RESULTS: VEGF -2578C and -2549D alleles
      were found to be ESRD causative alleles. It was observed that there was
      significant differences in the frequencies of the T allele of +936C/T
      polymorphism among CGN, HTN and CIN respectively. VEGF -1154AA genotype and A
      allele were associated significantly with CGN. T-G-A-D, T-A-C-I,C-G-A-D,C-A-C-D,C
      G-C-I,C-A-A-D and T-G-C-D were seven haplotypes concurred in all the ESRD
      patients irrespective of underlying disease. While C-G-C-D & C-G-A-I haplotypes
      showed risk association in CGN & CIN, C-A-C-I was observed to play predisposing
      role in HTN. CONCLUSION: The results highlight the role of studied VEGF
      polymorphisms in end stage renal disease at large and subsequently in the three
      primary kidney diseases among the North Indian population.

PMID- 22370608
TI  - Occurrence and behaviour of dissolved, nano-particulate and micro-particulate
      iron in waste waters and treatment systems: new insights from electrochemical
      analysis.
AB  - Cyclic-, Differential Pulse- and Steady-state Microdisc Voltammetry (CV, DPV,
      SMV) techniques have been used to quantify the occurrence and fate of dissolved
      Fe(ii)/Fe(iii), nano-particulate and micro-particulate iron over a 12 month
      period in a series of net-acidic and net-alkaline coal mine drainages and passive
      treatment systems. Total iron in the mine waters is typically 10-100 mg L(-1),
      with values up to 2100 mg L(-1). Between 30 and 80% of the total iron occurs as
      solid phase, of which 20 to 80% is nano-particulate. Nano-particulate iron
      comprises 20 to 70% of the nominally "dissolved" (i.e. <0.45 MUm) iron. Since
      coagulation and sedimentation are the only processes required to remove solid
      phase iron, these data have important implications for the generation or
      consumption of acidity during water treatment. In most waters, the majority of
      truly dissolved iron occurs as Fe(ii) (average 64 +/- 22%). Activities of Fe(ii)
      do not correlate with pH and geochemical modelling shows that no Fe(ii) mineral
      is supersaturated. Removal of Fe(ii) must proceed via oxidation and hydrolysis.
      Except in waters with pH < 4.4, activities of Fe(iii) are strongly and negatively
      correlated with pH. Geochemical modelling suggests that the activity of Fe(iii)
      is controlled by the solubility of hydrous ferric oxides and oxyhydroxysulfates,
      supported by scanning and transmission electron microscopic analysis of solids.
      Nevertheless, the waters are generally supersaturated with respect to
      ferrihydrite and schwertmannite, and are not at redox equilibrium, indicating the
      key role of oxidation and hydrolysis kinetics on water treatment. Typically 70
      100% of iron is retained in the treatment systems. Oxidation, hydrolysis,
      precipitation, coagulation and sedimentation occur in all treatment systems and -
      independent of water chemistry and the type of treatment system - hydroxides and
      oxyhydroxysulfates are the main iron sinks. The electrochemical data thus reveal
      the rationale for incomplete iron retention in individual systems and can thus
      inform future design criteria. The successful application of this low cost and
      rapid electrochemical method demonstrates its significant potential for real
      time, on-site monitoring of iron-enriched waters and may in future substitute
      traditional analytical methods.

PMID- 22370609
TI  - A highly efficient tree structure for the biosynthesis of heparan sulfate
      accounts for the commonly observed disaccharides and suggests a mechanism for
      domain synthesis.
AB  - The form of the biosynthetic pathway of the biologically and medically important
      polysaccharides heparan sulfate (HS) and the closely related heparin remain
      obscure despite significant progress characterising the biosynthetic machinery.
      Considering possible biosynthetic schemes using a graph approach and applying
      known constraints of enzyme order and specificity, a previously unreported system
      with a highly efficient tree structure emerged with two features: (1) All
      commonly occurring HS disaccharides could be synthesised through a common route,
      the major branch. (2) The least common disaccharides also occurred on a separate
      common branch, termed here the minor branch. This suggested that the relative
      abundance of these two sets of structures were the result of the specificity of a
      single enzyme (HS epimerase) acting at an early point in the scheme, to convert
      GlcA-GlcNS to IdoA-GlcNS in preference to converting GlcA-GlcNAc to IdoA-GlcNAc.
      A third key finding was that the common substrates for 3-O-sulfation all lie on
      the same (major) branch. The proposed scheme is consistent with a wide body of
      experiments comprising both biochemical data and results from HS biosynthetic
      enzyme knockout experiments in the literature. The major branch also contains a
      bifurcation, providing a choice of two distinct backbone geometries with the same
      charge. Further development of this novel biosynthetic scheme, in which frame
      shifts in the site of action of the enzymes were permitted to occur, while
      maintaining their order of action, suggested a mechanism by which domains could
      be generated, or further modification blocked. The relationship between the
      proposed pathway and the geometric and charge possibilities it allows were also
      explored.

PMID- 22370610
TI  - Cross-sectional study of treatment strategies on atrial fibrillation.
AB  - BACKGROUND: Despite the high prevalence and clinical importance of atrial
      fibrillation (AF), there is no Brazilian study describing the clinical profile of
      patients with AF and the most used treatment strategy (rhythm control vs. rate
      control). OBJECTIVE: Assess the most common treatment on AF in an outpatient
      specialized clinic for management of AF. In addition, the clinical profile of the
      population studied was provided. METHODS: Cross-sectional study assessing the
      most used strategy for atrial fibrillation control in 167 patients. The clinical
      profile was also described. A standardized form was used for data collection and
      statistical analysis was performed by SPSS 13.0 software. RESULTS: In This high
      risk population for thromboembolic events (61% had CHADS(2) >= 2), 54% of
      patients had paroxysmal or persistent AF, 96.6% were on vitamin K antagonists or
      acetylsalicylic acid, and 76.6% on beta-blocker (rate control 81,2% x rhythm
      control 58,8%; p < 0.05). Heart rate control was the most used strategy (79.5% x
      20.5%; p < 0.001). A statistical tendency towards more patients with ventricular
      dysfunction (15.2% x 2.9%; p = 0.06), CHADS(2) >= 2 (60.5% x 39.5%; p = 0.07) and
      heart valve diseases (25.8% x 11.8%; p = 0.08) was observed in the heart rate
      control group. CONCLUSION: In this high risk population for thromboembolic
      events, the rate control strategy was the most used.

PMID- 22370611
TI  - Vitamin D deficiency is associated with increased IL-17 and TNFalpha levels in
      patients with chronic heart failure.
AB  - BACKGROUND: Recent studies revealed a strong association between vitamin D (VD)
      status and chronic heart failure (CHF). It is now commonly considered that
      proinflammatory immune response underlies CHF development. OBJECTIVE: Since VD
      expresses anti-inflammatory properties, we investigated its impact on cytokines
      implicated in CHF, such as TNFalpha and IL-17, in patients suffering from CHF.
      METHODS: Blood was obtained from forty patients with CHF secondary to
      hypertension and/or coronary heart disease. VD status, IL-17 and TNFalpha levels
      were assessed using 25-hydroxy VD3 EIA and cytokine ELISAs. Clinical assessment
      and echocardiography was also performed. RESULTS: Elderly patients with CHF in
      Nis (Southeast Europe, latitude 43oN) exhibited 25-hydroxy VD3 levels below
      normal. Our data identified that patients with CHF secondary to hypertension have
      significantly lower 25-hydroxy VD3, increased TNFalpha and IL-17A levels in
      comparison to donors with CHF secondary to coronary disease. CONCLUSION: This
      study reveals that even in regions with a lot of sunny days VD deficiency
      represents a concerning issue. Data suggest that impaired VD status contributes
      to high IL-17 and TNFalpha levels and thereby may support CHF development.

PMID- 22370612
TI  - Blood pressure, metabolic and autonomic responses to insulin and intralipid(r)
      infusion in chagasic patients.
AB  - BACKGROUND: Intralipid((r)) and heparin infusion results in increased blood
      pressure and autonomic abnormalities in normal and hypertensive individuals.
      OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid((r)) and
      heparin (ILH) infusion on hemodynamic, metabolic, and autonomic response in
      patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients
      with the indeterminate form of Chagas' disease and 12 healthy volunteers were
      evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both
      groups. Plasma noradrenaline levels were slightly increased in the Chagas' group.
      After insulin tolerance testing (ITT), a significant decline was noted in glucose
      in both groups. ILH infusion resulted in increased blood pressure in both groups,
      but there was no significant change in plasma noradrenaline. The low-frequency
      component (LF) was similar and similarly increased in both groups. The high
      frequency component (HF) was lower in the Chagas' group. CONCLUSION: Patients
      with the indeterminate form of Chagas' disease had increased sympathetic activity
      at baseline and impaired response to insulin. They also had a lower high
      frequency component and impaired baroreflex sensitivity at baseline and during
      Intralipid((r)) and heparin infusion.

PMID- 22370613
TI  - Assessment of aortic valve area combining echocardiography and magnetic resonance
      imaging.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is routinely used to calculate
      aortic valve area (AVA) by continuity equation (CE). However, accurate
      measurement of the left ventricular outflow tract (LVOT) can be difficult and
      flow acceleration in the LVOT may lead to miscalculation of the AVA. OBJECTIVE:
      The aim of our study was to compare AVA measurements by standard TTE, cardiac
      magnetic resonance imaging (MRI) and a hybrid approach combining both techniques.
      METHODS: AVA was calculated in 38 patients (age 73+/-9 years) with standard TTE,
      cine-MRI planimetry and a hybrid approach: Hybrid Method 1: TTE-derived LVOT
      measurement in the CE numerator was replaced by the MRI assessment of the LVOT
      and AVA was calculated: (LVOT(MRI)/*LVOT-VTI(TTE))/transaortic-VTI(TTE). Method
      2: We replaced the SV in the numerator by the MRI-derived SV and calculated AVA =
      SV(MRI)/ transaortic-VTI(TTE). RESULTS: Mean AVA derived by TTE was 0.86 cm(2)+/
      0.23 cm(2) and 0.83 cm(2)+/-0.3 cm(2) by MRI- planimetry, respectively. The mean
      absolute difference in AVA was 0.03 cm(2) for TTE vs. MRI planimetry. AVA
      calculated with method 1 and method 2 was 1.23 cm(2)+/-0.4 cm(2) and 0.92 cm(2)+/
      0.32 cm(2), respectively. The mean absolute difference between TTE and method 1
      and method 2 was 0.37 cm(2) and 0.06 cm(2), respectively (p<0.001). CONCLUSION:
      MRI-planimetry of AVA and hybrid method 2 are accurate and showed a good
      agreement with standard TTE measurements. Therefore, hybrid method 1 is a
      reasonable alternative if poor acoustic windows or LVOT flow accelerations limit
      the accuracy of TTE, particularly in patients at high risk for an invasive
      hemodynamic study.

PMID- 22370614
TI  - Diagnosis and prognostic value of restrictive ventilatory disorders in the
      elderly: a systematic review of the literature.
AB  - Although less extensively studied compared to pulmonary obstructive diseases,
      restrictive lung disease (RLD) is highly prevalent and frequently disabling in
      the adult and, more, the elderly population. The underlying conditions may be
      either primarily pulmonary diseases, such as idiopathic pulmonary fibrosis, or
      non respiratory conditions secondarily affecting the lung, e. g. congestive heart
      failure, or else conditions affecting the lung expansion, e. g. obesity or rib
      cage deformity. The diagnosis is frequently based on the measurement of surrogate
      indexes such as the forced vital capacity (FVC) used as a proxy for total lung
      capacity (TLC). As a consequence, diagnosis of RLD is often characterized by poor
      specificity. In the elderly, worsening in the quality of life and poor prognosis
      are variably, but significantly, associated to RLD, being the underlying
      condition an important source of variability. Several causes of RLD are
      preventable and treatable conditions. A prompt identification of these conditions
      may allow to slow the decline of respiratory reserve and, thus, to preserve both
      personal independence and resistance to acute respiratory infections. This review
      gives an update on the latest evidence available on the prevalence and the
      prognosis of RLD in the elderly. Studies were identified through systematic
      searches of the electronic database MEDLINE. Reference list of eligible papers
      were also manually searched.

PMID- 22370615
TI  - Osmotic micropumps for drug delivery.
AB  - This paper reviews miniaturized drug delivery systems applying osmotic principles
      for pumping. Osmotic micropumps require no electrical energy and consequently
      enable drug delivery systems of smallest size for a broad field of new
      applications. In contrast to common tablets, these pumps provide constant (zero
      order) drug release rates. This facilitates systems for long term use not limited
      by gastrointestinal transit time and first-pass metabolism. The review focuses on
      parenteral routes of administration targeting drug delivery either in a site
      specific or systemic way. Osmotic pumps consist of three building blocks: osmotic
      agent, solvent, and drug. This is used to categorize pumps into (i) single
      compartment systems using water from body fluids as solvent and the drug itself
      as the osmotic agent, (ii) two compartment systems employing a separate osmotic
      agent, and (iii) multi-compartment architectures employing solvent, drug and
      osmotic agent separately. In parallel to the micropumps, relevant applications
      and therapies are discussed.

PMID- 22370616
TI  - Effect of Er,Cr:YSGG pretreatment on bond strength of fiber posts to root canal
      dentin using a self-adhesive resin cement.
AB  - The weak link in the adhesive luting of fiber posts to root canal dentin is at
      the cement-dentin interface. The aim of the present study was to evaluate the
      effect of Er,Cr:YSGG laser irradiation on push-out bond strength of fiber posts
      cemented to root canal dentin using a self-adhesive cement. A total of 30 sound
      human maxillary central incisors were equally divided into two groups after root
      canal treatment, decoronation and preparation of the post space. Teeth of group 1
      were treated with the Er,Cr:YSGG laser, and teeth of group 2 (control) received
      no laser treatment. After cementation of fiber posts with Maxcem self-adhesive
      cement, 3-mm cervical, middle and apical sections were prepared from the roots.
      Then a push-out test was performed using a universal testing machine at a strain
      rate of 0.5 mm/min. Data were analyzed using two-way ANOVA and the Bonferroni
      test. Statistical significance was defined as P < 0.05. There was a significant
      difference in the mean bond strength values between groups 1 and 2 (P = 0.001),
      but there were no significant differences between the various root parts (P =
      0.14). In addition, the cumulative effects of dentin treatment type and various
      root parts were not statistically significant (P = 0.41). The mean bond strength
      in the laser group was significantly higher than in the control group (P = 0.001,
      post hoc Bonferroni test).The failure mode was evaluated under a stereomicroscope
      at * 20 magnification.

PMID- 22370617
TI  - Effects of LLLT in combination with bisphosphonate on bone healing in critical
      size defects: a histological and histometric study in rat calvaria.
AB  - The purpose of this study was to analyze histologically the effect of low-level
      laser therapy (LLLT) in combination with bisphosphonate on bone healing in
      surgically created critical size defects (CSD) in rat calvaria. One hundred
      Wistar female rats sham operated (sham) and ovariectomized (Ovx) were maintained
      untreated for 1 month to allow for the development of osteopenia in the Ovx
      animals. A CSD was made in the calvarium of each rat, and the animals were
      divided into five groups according to following treatments: (1) sham rats
      (control), (2) Ovx rats, (3) Ovx rats treated with LLLT, (4) Ovx rats treated
      with bisphosphonate, and (5) Ovx rats treated with bisphosphonate and LLLT.
      Groups 4 and 5 were irrigated with 1 ml of bisphosphonate, and groups 3 and 5
      were submitted to LLLT (GaAlAs), 660 nm, 24 J, and 0.4285 W/cm(2) on the CSD. Ten
      animals of each treatment were killed at 30 and 60 days. Histomorphometric
      assessments, using image analysis software, and histological analyses were
      performed. No defect was completely regenerated with the bone. Histometrically,
      it can be observed that groups 3 (37.49 +/- 1.94%, 43.11 +/- 2.39%) and 5 (35.05
      +/- 1.57%, 41.07 +/- 1.89%) showed a significant bone neoformation when compared
      to groups 1 (16.81 +/- 1.57%, 27.54 +/- 1.49%), 2 (11.68 +/- 0.98%, 22.51 +/-
      1.05%), and 4 (14.62 +/- 1.70%, 25.67 +/- 1.41%) in all experimental periods (P <
      0.05). It was possible to conclude that the LLLT associated or not with
      bisphosphonate treatment was effective for stimulating bone formation in CSD in
      the calvaria of rats submitted to ovariectomy.

PMID- 22370618
TI  - Novel treatment strategy for refractory hemorrhagic cystitis following radiation
      treatment of genitourinary cancer: Use of 980-nm diode laser.

PMID- 22370619
TI  - Protective effect of CO2 laser (10.6 MUm) and fluoride on enamel erosion in
      vitro.
AB  - The aim of this study was to analyze the effect of CO(2) laser (10.6 MUm)
      irradiation with 5-MUs pulse width in prevention of enamel erosion due to citric
      acid exposure in vitro. One hundred forty-four bovine enamel samples were cut
      into 5 * 5 * 2-mm-size slabs and polished to obtain plane surfaces. Enamel
      surfaces were covered with acid-resistant varnish, except for a central area of
      2.5 mm in diameter. The samples were divided into four groups (n = 12/group/day):
      C-control, no treatment; L-CO(2) laser irradiation (0.3 J/cm(2), 5 MUs, 226 Hz);
      F-topical fluoride treatment, 1.25%F(-) (AmF/NaF) for 3 min; and FL-fluoride
      treatment + CO(2) laser. For erosive demineralization, samples were immersed in
      40 ml of citric acid (0.05 M, pH 2.3) for 20 min two times per day during 5 days.
      After 1, 3, and 5 days, surface loss was measured by digital profilometer.
      According to the repeated measure ANOVA and post hoc comparisons, all the
      treatments showed statistically significant reduction of enamel loss as compared
      to control group, in all investigated times (p < 0.0001): L (52%,31%,37%); F
      (28%,24%,29%); FL (73%,55%,57%). Both CO(2) laser irradiation alone (L) and the
      combined laser-fluoride treatment (FL) caused less enamel loss than the fluoride
      group (F) in all days (p < 0.0001 for L in all times; and p < 0.0001, p = 0.0220
      and p = 0.0051 for F, respectively, at days 1, 3, and 5). Under the conditions of
      this study, CO(2) laser irradiation (0.3 J/cm(2), 5 MUs, 226 Hz) could
      effectively reduce enamel surface loss due to citric acid exposure, in vitro.
      This effect was still observed after 5 days of repeated acid exposures.

PMID- 22370621
TI  - Panic.

PMID- 22370620
TI  - Effect of low-level laser therapy on healing of tenotomized Achilles tendon in
      streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus (DM) is associated with musculoskeletal damage. Investigations
      have indicated that healing of the surgically tenotomized Achilles tendon was
      considerably augmented following low-level laser therapy (LLLT) in non-diabetic,
      healthy animals. The aim of the present study was to evaluate the effect of LLLT
      on the Achilles tendon healing in streptozotocin-induced diabetic (STZ-D) rats
      via a biomechanical evaluating method. Thirty-three rats were divided into non
      diabetic (n = 18) and diabetic (n = 15) groups. DM was induced in the rats by
      injections of STZ. The right Achilles tendons of all rats were tenotomized 1
      month after STZ injections. The two experimental groups (n = 6 for each group) of
      non-diabetic rats were irradiated with a helium-neon (He-Ne) laser at 2.9 and
      11.5 J/cm(2) for ten consecutive days. The two experimental groups of diabetic
      rats (n = 5 for each group) were irradiated with a He-Ne laser at 2.9 and 4.3
      J/cm(2) for ten consecutive days. The tendons were submitted to a tensiometric
      test. Significant improvements in the maximum stress (MS) values (Newton per
      square millimeter) were found following LLLT at 2.9 J/cm(2) in both the non
      diabetic (p = 0.031) and diabetic (p = 0.019) experimental groups when compared
      with their control groups. LLLT at 2.9 J/cm(2) to the tenotomized Achilles
      tendons in the non-diabetic and diabetic rats significantly increased the
      strength and MS of repairing Achilles tendons in our study.

PMID- 22370622
TI  - Fragment one.

PMID- 22370623
TI  - Walking to Danville.

PMID- 22370625
TI  - Hetastarch-induced osmotic nephrosis.

PMID- 22370626
TI  - The detrimental influence of bacteria (E. coli, Shigella and Salmonella) on the
      degradation of organic compounds (and vice versa) in TiO2 photocatalysis and near
      neutral photo-Fenton processes under simulated solar light.
AB  - TiO2 photocatalytic and near-neutral photo-Fenton processes were tested under
      simulated solar light to degrade two models of natural organic matter -
      resorcinol (R) (which should interact strongly with TiO2 surfaces) and
      hydroquinone (H) - separately or in the presence of bacteria. Under similar
      oxidative conditions, inactivation of Escherichia coli, Shigella sonnei and
      Salmonella typhimurium was carried out in the absence and in the presence of 10
      mg L(-1) of R and H. The 100% abatement of R and H by using a TiO2 photocatalytic
      process in the absence of bacteria was observed in 90 min for R and in 120 min
      for H, while in the presence of microorganisms abatement was only of 55% and 35%
      for R and H, respectively. Photo-Fenton reagent at pH 5.0 completely removed R
      and H in 40 min, whereas in the presence of microorganisms their degradation was
      of 60% to 80%. On the other hand, 2 h of TiO2 photocatalytic process inactivated
      S. typhimurium and E. coli cells in three and six orders of magnitude,
      respectively, while S. sonnei was completely inactivated in 10 min. In the
      presence of R or H, the bacterial inactivation via TiO2 photocatalysis was
      significantly decreased. With photo-Fenton reagent at pH 5 all the microorganisms
      tested were completely inactivated in 40 min of simulated solar light irradiation
      in the absence of organics. When R and H were present, bacterial photo-Fenton
      inactivation was less affected. The obtained results suggest that in both TiO2
      and iron photo-assisted processes, there is competition between organic
      substances and bacteria simultaneously present for generated reactive oxygen
      species (ROS). This competition is most important in heterogeneous systems,
      mainly when there are strong organic-TiO2 surface interactions, as in the
      resorcinol case, suggesting that bacteria-TiO2 interactions could play a key role
      in photocatalytic cell inactivation processes. 

PMID- 22370627
TI  - Accuracy of estrogen receptor, progesterone receptor, and HER2 status between
      core needle and open excision biopsy in breast cancer: a meta-analysis.
AB  - Accurate determination of estrogen receptor (ER), progesterone receptor (PgR),
      and human epidermal growth factor receptor-2 (HER2) status was very important in
      selecting breast cancer treatment. Discordance of ER, PR, and HER2 status between
      core needle biopsy (CNB) and open excision biopsy (OEB) varied among reported
      studies. We performed a meta-analysis to compare the accuracy of CNB with that of
      OEB for ER, PgR, and HER2 status detection in breast cancer. Medical subject
      heading (MeSH) terms (Breast Neoplasm) and key words (biopsy OR mammotome) AND
      (incision OR excision OR surgery) AND (estrogen OR progesterone OR HER2 OR
      hormone). Patients with HER2 immunohistochemical 3+ or fluorescence in situ
      hybridization positive were classified into HER2[b] group. A total of 27 studies
      were eligible in this study. Aggregate positive ER and PgR rate was 80.0 and
      69.5% for CNB; and 77.7 and 66.2% for OEB, respectively. The HER2 positive rate
      difference between CNB and OEB was only 0.2%. The pooled sensitivity of
      evaluating ER, PgR, and HER2 status in CNB compared with OEB was 0.970, 0.911,
      and 0.799 (0.813 for HER2[b]), respectively. All of AUC values for these status
      determination were larger than 0.9. Heterogeneity between studies was introduced
      by various factors in PgR and HER2[b] analysis. Subgroup analysis showed that the
      specificity and OR of CNB in studies with ER positive rate >78% was lower than
      studies with ER positive rate <=78% (P < 0.05). This meta-analysis indicated that
      CNB had high diagnostic accuracy in evaluating ER, PgR, and HER2 status compared
      with OBE in breast cancer patients. In terms of 2-3% positive rate difference, ER
      and PgR status should be detected both on CNB and OEB samples, especially to
      retest their expression on CNB in patients with hormonal receptor negative tumors
      in OEB.

PMID- 22370628
TI  - Effect of CYP3A4 inducer dexamethasone on hepatotoxicity of lapatinib: clinical
      and in vitro evidence.
AB  - Concomitant usage of lapatinib, a cytochrome P450 (CYP) 3A4 substrate and
      dexamethasone, a CYP3A4 inducer, is a pharmacokinetic drug-drug interaction. This
      combination may increase the formation of reactive lapatinib metabolites, which
      is potentially hepatotoxic. This study aims to evaluate the clinical effect of
      dexamethasone on incidence of hepatotoxicity and to ascertain its in vitro role
      using a parallel cell culture model experimental setup. Clinical effects of
      dexamethasone on lapatinib-induced hepatotoxicity were evaluated in a nested case
      control study based on 120 patient data obtained from our records. For the in
      vitro experiment, metabolically competent transforming growth factor alpha mouse
      hepatocytes (TAMH) were treated with lapatinib and viabilities were compared in
      the presence or absence of dexamethasone. After adjusting for confounders,
      patients receiving the combination were 4.57 times (95% CI 1.23-16.88, p = 0.02)
      more likely to develop hepatotoxicity and 3.48 times (95% CI 1.24-9.80, p = 0.02)
      more likely to develop a clinically important change in alanine aminotransferase
      than compared to the other group. Treatment of TAMH cells with lapatinib and
      dexamethasone caused a further reduction in viability, as compared to treatment
      with lapatinib alone. At 5 MUM lapatinib, the introduction of dexamethasone 20
      MUM produced a 59% decline in viability. This is the first study to document a
      clinically important interaction between lapatinib and dexamethasone, which
      associates with an increased occurrence of hepatotoxicity. The in vitro findings
      have provided substantiating evidence and insights on the role of dexamethasone
      in lapatinib-induced hepatotoxicity.

PMID- 22370629
TI  - Evaluation of RAD51C as cancer susceptibility gene in a large breast-ovarian
      cancer patient population referred for genetic testing.
AB  - Despite extensive analysis of the BRCA1 and BRCA2 genes, germline mutations are
      detected in <20% of families with a presumed genetic predisposition for breast
      and ovarian cancer. Recent literature reported RAD51C as a new breast cancer
      susceptibility gene. In this study, we report the analysis of 410 patients from
      351 unrelated pedigrees. All were referred for genetic testing and we selected
      families with at least one reported case of ovarian cancer in which BRCA1&2
      mutations were previously ruled out. We analyzed the coding exons, intron-exons
      boundaries, and UTRs of RAD51C. Our mutation analysis did not reveal any
      unequivocal deleterious mutation. In total 12 unique sequence variations were
      identified of which two were novel. Our study and others suggest a low prevalence
      of RAD51C mutations with an exception for some founder populations. This
      observation is in favor of the rare allele hypothesis in the debate over the
      nature of the genetic contribution to individual susceptibility to breast and
      ovarian cancer and further genome-wide studies in high risk families are
      warranted.

PMID- 22370630
TI  - Development of a unilaterally-lesioned 6-OHDA mouse model of Parkinson's disease.
AB  - The unilaterally lesioned 6-hyroxydopamine (6-OHDA)-lesioned rat model of
      Parkinson's disease (PD) has proved to be invaluable in advancing our
      understanding of the mechanisms underlying parkinsonian symptoms, since it
      recapitulates the changes in basal ganglia circuitry and pharmacology observed in
      parkinsonian patients(1-4). However, the precise cellular and molecular changes
      occurring at cortico-striatal synapses of the output pathways within the
      striatum, which is the major input region of the basal ganglia remain elusive,
      and this is believed to be site where pathological abnormalities underlying
      parkinsonian symptoms arise(3,5).    In PD, understanding the mechanisms
      underlying changes in basal ganglia circuitry following degeneration of the nigro
      striatal pathway has been greatly advanced by the development of bacterial
      artificial chromosome (BAC) mice over-expressing green fluorescent proteins
      driven by promoters specific for the two striatal output pathways (direct
      pathway: eGFP-D1; indirect pathway: eGFP-D2 and eGFP-A2a)(8), allowing them to be
      studied in isolation. For example, recent studies have suggested that there are
      pathological changes in synaptic plasticity in parkinsonian mice(9,10). However,
      these studies utilised juvenile mice and acute models of parkinsonism. It is
      unclear whether the changes described in adult rats with stable 6-OHDA lesions
      also occur in these models. Other groups have attempted to generate a stable
      unilaterally-lesioned 6-OHDA adult mouse model of PD by lesioning the medial
      forebrain bundle (MFB), unfortunately, the mortality rate in this study was
      extremely high, with only 14% surviving the surgery for 21 days or longer(11).
      More recent studies have generated intra-nigral lesions with both a low mortality
      rate >80% loss of dopaminergic neurons, however expression of L-DOPA induced
      dyskinesia(11,12,13,14) was variable in these studies. Another well established
      mouse model of PD is the MPTP-lesioned mouse(15). Whilst this model has proven
      useful in the assessment of potential neuroprotective agents(16), it is less
      suitable for understanding mechanisms underlying symptoms of PD, as this model
      often fails to induce motor dei!?cits, and shows a wide variability in the extent
      of lesion(17, 18).    Here we have developed a stable unilateral 6-OHDA-lesioned
      mouse model of PD by direct administration of 6-OHDA into the MFB, which
      consistently causes >95% loss of striatal dopamine (as measured by HPLC), as well
      as producing the behavioural imbalances observed in the well characterised
      unilateral 6-OHDA-lesioned rat model of PD. This newly developed mouse model of
      PD will prove a valuable tool in understanding the mechanisms underlying
      generation of parkinsonian symptoms.

PMID- 22370631
TI  - Investigation of multiple electronic excited state relaxation pathways following
      200 nm photolysis of gas-phase imidazole.
AB  - Imidazole acts as a subunit in the DNA base adenine and the amino acid histidine
      both important biomolecules which display low fluorescence quantum yields
      following UV excitation. The low fluorescence quantum yields are attributed to
      competing non-radiative excited state relaxation pathways that operate on
      ultrafast timescales. Imidazole is investigated here as a model compound due to
      its accessibility to high level ab initio calculations and time-resolved gas
      phase spectroscopic techniques. Recent non-adiabatic dynamics simulations have
      identified three non-radiative relaxation mechanisms which are active following
      6.0-6.2 eV excitation. Presented herein is a comprehensive investigation of each
      mechanism using a combination of femtosecond time-resolved ion yield and total
      kinetic energy release spectroscopies to monitor the formation of associated
      photoproducts. Relaxation along the (1)pisigma state constitutes the predominant
      deactivation pathway. Timescales for NH-dissociation are extracted and
      distinguished from alternative H-atom sources based on their kinetic energy
      distributions. Larger photoproducts are observed to a lesser extent and
      attributed to ring fragmentation following NH-puckering and CN-stretching
      relaxation paths.

PMID- 22370632
TI  - Generation of dopaminergic neurons directly from mouse fibroblasts and fibroblast
      derived neural progenitors.

PMID- 22370633
TI  - The microRNA pathway controls germ cell proliferation and differentiation in C.
      elegans.
AB  - The discovery of the miRNA pathway revealed a new layer of molecular control of
      biological processes. To uncover new functions of this gene regulatory pathway,
      we undertook the characterization of the two miRNA-specific Argonaute proteins in
      Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of
      function of alg-1 and alg-2 genes resulted in reduced progeny number. An
      extensive analysis of the germline of these mutants revealed a reduced mitotic
      region, indicating fewer proliferating germ cells. We also observed an early
      entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2
      protein expressions in the distal tip cell (DTC), a specialized cell located at
      the tip of both C. elegans gonadal arms that regulates mitosis-meiosis
      transition. Re-establishing the expression of alg-1 specifically in the DTC of
      mutant animals partially rescued the observed germline defects. Further analyses
      also support the implication of the miRNA pathway in gametogenesis.
      Interestingly, we observed that disruption of five miRNAs expressed in the DTC
      led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant
      gonads suggests that the miRNA pathway is involved in the regulation of different
      pathways important for germline proliferation and differentiation. Collectively,
      our data indicate that the miRNA pathway plays a crucial role in the control of
      germ cell biogenesis in C. elegans.

PMID- 22370634
TI  - MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma
      cells.
AB  - When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle
      proteins like c-myc, continuing tumor cell growth depends on cap-independent
      translation, which is mediated by internal ribosome entry sites (IRESes) located
      in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog
      induced activation of MNK kinases had a role in such IRES activity, we studied
      multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM
      cell lines and primary specimens by a mitogen-activated protein kinase-dependent
      mechanism. Pharmacological inhibition of MNK activity or genetic silencing of
      MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although
      RAP, used alone, had little effect on myc protein expression, when combined with
      a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no
      inhibition of myc RNA, consistent with an effect on myc translation. In a RAP
      resistant MM cell lines as well as a resistant primary MM specimen, co-exposure
      to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP
      induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts
      additionally supported a role for MNK kinases in RAP-induced myc IRES
      stimulation. These results indicate that MNK kinase activity has a critical role
      in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited.
      As kinase activity also regulated sensitivity to RAP, the data also provide a
      rationale for therapeutically targeting MNK kinases for combined treatment with
      mTOR inhibitors.

PMID- 22370635
TI  - Integrin alpha9beta1 promotes malignant tumor growth and metastasis by
      potentiating epithelial-mesenchymal transition.
AB  - The integrin alpha9beta1 binds a number of extracellular matrix components to
      mediate cell adhesion, migration and tissue invasion. Although expressed in a
      variety of normal human cells including endothelium, it is also expressed in
      cancer cells. We have previously shown that alpha9beta1 binds VEGF-A to
      facilitate angiogenesis, an important component of the tumor microenvironment. As
      alpha9beta1 induces accelerated cancer cell migration, we wished to determine
      what role it played in cancer growth and metastasis. In this study, we show that
      alpha9beta1 expression induces molecular changes consistent with epithelial
      mesenchymal transition. In addition, we found that alpha9beta1 forms a tri
      partite protein complex with beta-catenin and E-cadherin, which dissociates
      following integrin activation and subsequent src and beta-catenin
      phosphorylation. These findings were consistent in cells in which: alpha9beta1
      was exogenously over-expressed, or when its expression was suppressed in cancer
      cells endogenously expressing alpha9beta1. These in vitro results are
      biologically significant as alpha9beta1-expressing cancer cells induce greater
      tumor growth and metastases in mice as compared to the cells without alpha9beta1
      expression or when integrin expression is suppressed. Furthermore, integrin
      alpha9beta1 is expressed in primary human small cell lung cancer and patients
      having a high expression of alpha9beta1 demonstrated significantly worse long
      term survival compared with patients with low alpha9beta1 expression. These
      findings highlight a novel mechanism of integrin alpha9beta1 function in human
      cancer.

PMID- 22370637
TI  - miR-34c may protect lung cancer cells from paclitaxel-induced apoptosis.
AB  - MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that negatively
      regulate the expression of their target genes. They are involved in many
      biological processes, including cell proliferation, apoptosis and
      differentiation, and are considered as promising new therapeutic targets for
      cancer. However, the identity of miRNAs involved in apoptosis and their
      respective targets remain largely unknown. Given the elevated complexity of miRNA
      regulation of gene expression, we performed a functional screening as an
      alternative strategy to identify those miRNAs that in lung cancer cells may
      interfere with the apoptotic process. To this aim, we generated a derivative of
      the non-small cell lung carcinoma A549 cell line in which caspase-8, a critical
      upstream initiator of apoptosis, can be activated by administration of the small
      dimerizer drug AP20187. We found a number of miRNAs that may rescue cell
      viability from caspase-8 activation. They included miRNAs already described as
      oncogenic such as miR-17, miR-135 and miR-520, but also some miRNAs such as miR
      124-1 and miR-34c for which a tumor-suppressive role has instead been described
      or expected. Among them, miR-34c-5p markedly increased resistance to paclitaxel
      induced apoptosis. We demonstrate that Bmf (Bcl-2-modifying factor) is a target
      of miR-34c-5p, and that its silencing, together with that of c-myc, a known
      target of miR-34c-5p, contributes to resistance to apoptosis induced by
      paclitaxel through p53 downregulation.

PMID- 22370636
TI  - Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes
      mammary tumorigenesis and emergence of mutations.
AB  - Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K)
      catalytic subunit p110alpha, occur in ~25% of human breast cancers. In this
      study, we report the development of a knock-in mouse model for breast cancer
      where the endogenous Pik3ca allele was modified to allow tissue-specific
      conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R))
      mutant allele. We found that activation of the latent Pik3ca(H1047R) allele
      resulted in breast tumors with multiple histological types. Whole-exome analysis
      of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations,
      including Trp53 mutations that appeared spontaneously during the development of
      adenocarinoma and spindle cell tumors. Further, we used this model to test the
      efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that
      the tumors respond to PI3K inhibition.

PMID- 22370639
TI  - Zinc-finger protein 331, a novel putative tumor suppressor, suppresses growth and
      invasiveness of gastric cancer.
AB  - Zinc-finger protein 331 (ZNF331), a Kruppel-associated box zinc-finger protein
      gene, was identified as a putative tumor suppressor in our previous study.
      However, the role of ZNF331 in tumorigenesis remains elusive. We aimed to clarify
      its epigenetic regulation and biological functions in gastric cancer. ZNF331 was
      silenced or downregulated in 71% (12/17) gastric cancer cell lines. A significant
      downregulation was also detected in paired gastric tumors compared with adjacent
      non-cancer tissues. In contrast, ZNF331 was readily expressed in various normal
      adult tissues. The downregulation of ZNF331 was closely linked to the promoter
      hypermethylation as evidenced by methylation-specific PCR, bisulfite genomic
      sequencing and reexpression by demethylation agent treatment. DNA sequencing
      showed no genetic mutation/deletion of ZNF331 in gastric cancer cell lines.
      Ectopic expression of ZNF331 in the silenced cancer cell lines MKN28 and HCT116
      significantly reduced colony formation and cell viability, induced cell cycle
      arrests and repressed cell migration and invasive ability. Concordantly,
      knockdown of ZNF331 increased cell viability and colony formation ability of
      gastric cancer cell line MKN45. Two-dimensional gel electrophoresis and mass
      spectrometry-based comparative proteomic approach were applied to analyze the
      molecular basis of the biological functions of ZNF331. In all, 10 downstream
      targets of ZNF331 were identified to be associated with regulation of cell growth
      and metastasis. The tumor-suppressive effect of ZNF331 is mediated at least by
      downregulation of genes involved in cell growth promotion (DSTN, EIF5A, GARS,
      DDX5, STAM, UQCRFS1 and SET) and migration/invasion (DSTN and ACTR3), and
      upregulation of genome-stability gene (SSBP1) and cellular senescence gene
      (PNPT1). A novel target of ZNF331 (DSTN) was functionally validated.
      Overexpression of DSTN in BGC-823 cells increased colony formation and migration
      ability. In conclusion, our results suggest that ZNF331 possesses important
      functions for the suppression of gastric carcinogenesis as a novel functional
      tumor-suppressor gene.

PMID- 22370638
TI  - Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context
      of Trp53 heterozygosity.
AB  - We performed a genetic screen in mice to identify candidate genes that are
      associated with leukaemogenesis in the context of Trp53 heterozygosity. To do
      this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11
      transposase alleles to allow transposon-mediated insertional mutagenesis to
      occur. From the resulting leukaemias/lymphomas that developed in these mice, we
      identified nine loci that are potentially associated with tumour formation in the
      context of Trp53 heterozygosity, including AB041803 and the Jun dimerization
      protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53
      promoter, via an atypical AP-1 site, and that Jdp2 expression negatively
      regulates Trp53 expression levels. This study is the first to identify a genetic
      mechanism for tumour formation in the context of Trp53 heterozygosity.

PMID- 22370641
TI  - WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin
      in human gastric cancer cells.
AB  - Resistance to chemotherapy is a major obstacle for curative treatment of human
      gastric cancer (GC). However, the underlying molecular mechanisms are largely
      unknown. Wingless-type MMTV integration site family members (WNTs) are secreted
      glycoproteins involved in embryogenesis and, on inappropriate expression in the
      adult, in cancer. Here, we show expression of WNT6 in GC patient specimens, human
      GC cell lines and in a mouse model of GC. In human GC cells, WNT6 expression was
      enhanced by caveolin-1 (Cav1), a scaffold protein of plasma membrane caveolae.
      WNT6 knock-down and overexpression experiments demonstrated that WNT6 increased
      the resistance to apoptotic cell death induced by the anthracycline
      chemotherapeutics epirubicin (Epi) and doxorubicin (Dox). Epi increased the
      activity of the human WNT6 promoter through Cav1-dependent binding of beta
      catenin to the proximal WNT6 promoter. Epi increased both WNT6/Wnt6 and Cav1
      expression in human GC cells and within the tumor area of a murine model of GC
      (CEA424-SV40 TAg). In GC patients, WNT6 expression was positively associated with
      the tumor stage and the nodal status, and inversely correlated with the response
      to ECF (Epi, cisplatin, 5-fluorouracil) chemotherapy. These results showed that
      WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of
      GC cells to anthracycline drugs. Understanding the molecular mechanisms driving
      WNT6/Cav1-induced drug resistance will provide benefits in developing new
      therapies for GC.

PMID- 22370640
TI  - MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4.
AB  - Murine double minute (MDM2) binding protein (MTBP) has been implicated in cancer
      progression. Here, we demonstrate one mechanism by which MTBP inhibits cancer
      metastasis. Overexpression of MTBP in human osteosarcoma cell lines lacking wild
      type p53 did not alter primary tumor growth in mice, but significantly inhibited
      metastases. MTBP downregulation increased the migratory potential of MDM2(-/
      )p53(-/-) mouse embryonic fibroblasts, suggesting that MTBP inhibited cell
      migration independently of the Mdm2-p53 pathway. Co-immunoprecipitation and mass
      spectrometric analysis identified alpha-actinin-4 (ACTN4) as an MTBP-interacting
      protein. Endogenous MTBP interacted with and partially colocalized with ACTN4.
      MTBP overexpression inhibited cell migration and filopodia formation mediated by
      ACTN4. Increased cell migration by MTBP downregulation was inhibited by
      concomitant downregulation of ACTN4. MTBP also inhibited ACTN4-mediated F-actin
      bundling. We furthermore demonstrated that nuclear localization of MTBP was
      dispensable for inhibiting ACTN4-mediated cell migration and filopodia formation.
      Thus, MTBP suppresses cell migration, at least partially, by inhibiting ACTN4
      function. Our study not only provides a mechanism of metastasis suppression by
      MTBP, but also suggests MTBP as a potential biomarker for cancer progression.

PMID- 22370642
TI  - The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with
      transactivation domains.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2, NM 006164, 605 AA) is
      essential for the antioxidant responsive element (ARE)-mediated expression of a
      group of detoxifying antioxidant genes that detoxify carcinogens and protect
      against oxidative stress. Several proteins have been identified as Nrf2
      interacting molecules. In this study, we found that the overexpression of
      receptor-associated coactivator 3 (RAC3)/AIB-1/steroid receptor coactivator-3, a
      nuclear coregulator and oncogene frequently amplified in human breast cancers,
      induced heme oxygenase-1 (HO-1) through Nrf2 transactivation in HeLa cells. Next,
      we determined the interaction between RAC3 and Nrf2 proteins using a co
      immunoprecipitation assay and fluorescence resonance energy transfer analysis.
      The results showed that RAC3 bound directly to the Nrf2 protein in the nucleus.
      Subsequently, we identified the interacting domains of Nrf2 and RAC3 using a
      glutathione S-transferase pull-down assay. The results showed that both the N
      terminal RAC3-pasB and C-terminal RAC3-R3B3 domains were tightly bound to the
      Neh4 and Neh5 transactivation domains. Furthermore, chromatin immunoprecipitation
      showed that RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter
      via Nrf2 binding. These data suggest that Nrf2 activation is modulated and
      directly controlled through interactions with the RAC3 protein in HeLa cells.

PMID- 22370644
TI  - The molecular mechanism of microRNA-145 to suppress invasion-metastasis cascade
      in gastric cancer.
AB  - Invasion and metastasis are the major features of malignant tumors that are
      responsible for 90% of cancer-related deaths. Recently, microRNAs have been
      discovered to have a role in suppressing tumor metastasis. This study's aim was
      to clarify the roles of miR-145 in gastric carcinomas and its underlying
      molecular mechanism in regulating tumor metastasis. Here, we demonstrate a
      stepwise downregulation of miR-145 level in nontumorous gastric mucosa, primary
      gastric cancers and their secondary metastases. In vitro analysis of miR-145's
      ectopic expression and loss-of-function suggests that it suppresses gastric
      cancer cell migration and invasion. In vivo spontaneous metastasis and
      experimental metastasis assay further confirm its function in suppressing the
      invasion-metastasis cascade, including impairing local invasion and inhibiting
      hematogenous metastasis in gastric cancers. Furthermore, we identified a novel
      mechanism of miR-145 to suppress metastasis. N-cadherin (CDH2) was proved to be a
      direct target of miR-145, using luciferase assay and western blot. Re-expressing
      N-cadherin in miR-145-transfected cells reverses their migration and invasion
      defects. Although not a direct target of miR-145, matrix metallopeptidase 9
      (MMP9), but not MMP2, was also significantly decreased in miR-145-expressing
      cells. We suggest that miR-145 suppresses tumor metastasis by inhibiting N
      cadherin protein translation, and then indirectly downregulates its downstream
      effector MMP9.

PMID- 22370643
TI  - MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug
      independent mechanisms.
AB  - Epithelial-mesenchymal transition (EMT) is a developmental program of signaling
      pathways that determine commitment to epithelial and mesenchymal phenotypes. In
      the prostate, EMT processes have been implicated in benign prostatic hyperplasia
      and prostate cancer progression. In a model of Pten- and TP53-null prostate
      adenocarcinoma that progresses via transforming growth factor beta-induced EMT,
      mesenchymal transformation is characterized by plasticity, leading to various
      mesenchymal lineages and the production of bone. Here we show that SLUG is a
      major regulator of mesenchymal differentiation. As microRNAs (miRs) are
      pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR
      expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced
      with progression of prostate adenocarcinoma, and we identify Slug as one of the
      phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a
      direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200
      act in a self-reinforcing regulatory loop, leading to amplification of EMT.
      Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression
      of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model
      systems. Various miR targets were analyzed, and our findings suggest that miR-1
      has roles in regulating EMT and mesenchymal differentiation through Slug and
      functions in tumor-suppressive programs by regulating additional targets.

PMID- 22370645
TI  - Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug
      resistant non-small cell lung cancer cells.
AB  - The hypothesis of cancer stem cells has been proposed to explain the therapeutic
      failure in a variety of cancers including lung cancers. Previously, we
      demonstrated acquisition of epithelial-mesenchymal transition, a feature highly
      reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells
      (A549/GR). Here, we show that A549/GR cells contain a high proportion of CXCR4+
      cells that are responsible for having high potential of self-renewal activity in
      vitro and tumorigenicity in vivo. A549/GR cells exhibited strong sphere-forming
      activity and high CXCR4 expression and SDF-1alpha secretion compared with parent
      cells. Pharmacological inhibition (AMD3100) and/or siRNA transfection targeting
      CXCR4 significantly suppressed sphere-forming activity in A549 and A549/GR cells,
      and in various non-small cell lung cancer (NSCLC) cell lines. A549/GR cells
      showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. Pharmacological
      inhibition of phosphatidyl inositol 3-kinase or transfection with wild-type PTEN
      suppressed phosphorylation of Akt, mTOR and STAT3 (Y705), sphere formation, and
      CXCR4 expression in A549/GR cells, whereas mutant PTEN enhanced these events.
      Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere
      formation, but not CXCR4 expression, indicating that STAT3 is a downstream
      effector of CXCR4-mediated signaling. FACS-sorted CXCR4+ A549/GR cells formed
      many large spheres, had self-renewal capacity, demonstrated radiation resistance
      in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4- cells.
      Lentiviral-transduction of CXCR4 enhanced sphere formation and tumorigenicity in
      H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities
      in A549/GR cells. Our data indicate that CXCR4+ NSCLC cells are strong candidates
      for tumorigenic stem-like cancer cells that maintain stemness through a CXCR4
      medated STAT3 pathway and provide a potential therapeutic target for eliminating
      these malignant cells in NSCLC.

PMID- 22370646
TI  - Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant
      pleural effusion.
AB  - Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and regulates
      tumor-associated angiogenesis and inflammation, both central to the pathogenesis
      of malignant pleural effusion (MPE). Here, we examined the impact of tumor- and
      host-derived SPP1 in MPE formation and explored the mechanisms by which the
      cytokine exerts its effects. We used a syngeneic murine model of lung
      adenocarcinoma-induced MPE. To dissect the effects of tumor- versus host-derived
      SPP1, we intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with
      either wild-type or SPP1-deficient syngeneic lung cancer cells. We demonstrated
      that both tumor- and host-derived SPP1 promoted pleural fluid accumulation and
      tumor dissemination in a synergistic manner (P<0.001). SPP1 of host origin
      elicited macrophage recruitment into the cancer-affected pleural cavity and
      boosted tumor angiogenesis, whereas tumor-derived SPP1 curtailed cancer cell
      apoptosis in vivo. Moreover, the cytokine directly promoted vascular hyper
      permeability independently of vascular endothelial growth factor. In addition,
      SPP1 of tumor and host origin differentially affected the expression of
      proinflammatory and angiogenic mediators in the tumor microenvironment. These
      results suggest that SPP1 of tumor and host origin impact distinct aspects of MPE
      pathobiology to synergistically promote pleural fluid formation and pleural tumor
      progression. SPP1 may present an attractive target of therapeutic interventions
      for patients with MPE.

PMID- 22370647
TI  - Testing NLCLiP: validation of estimates of rates of non-problematic and
      problematic gambling in a sample of British schoolchildren.
AB  - This paper reports on the results of applying a short screen for problem
      gambling, called NLCLiP, to a national sample of 8,958 British schoolchildren
      under the age of 16. It shows that, in its current form, NLCLiP can, with
      reasonable accuracy, be employed to estimate the rate of prevalence of
      problematic and non-problematic (i.e. gambling which does not lead to significant
      endorsement of DSM-IV-MR-J criteria) in a general population of children.
      However, NLCLiP does not reliably discriminate between problem and at risk
      gamblers. Moreover, it does not provide a reliable basis to identify cases of
      problem gambling. The main conclusion reached is that NLCLiP is a potentially
      useful tool for regulators to assess changes in the prevalence of problematic and
      non-problematic gambling among children over time.

PMID- 22370648
TI  - Estimation of sediment accumulation rates using naturally occuring 210Pb models
      in Gulbahce Bay, Aegean Sea, Turkey.
AB  - The sediment chronology was determined using Lead-210 (210Pb) dating method in
      Gulbahce Bay. Sediment cores were obtained using gravity core sampler from
      hydrothermal area and also from reference point and surfical distribution of
      Polonium-210 (210Pb) was investigated in the study area. The average of surfical
      concentration of 210Po was found as 175.25 +/- 3.80 Bq kg-1 in the hydrothermal
      area which was higher than the reference point value of 133.20 +/- 3.30 Bq kg-1.
      Sedimentation rates in Core reference point (RN) displayed an increase till the
      year 1942 and a decrease afterwards, sedimentation rates in any core from
      hydrothermal area have not exhibited any continuous increase or decrease. The
      210Pb fluxes measured from core inventories are close to each other. Average
      enrichment factors for Cu, Cd, Sr, Zn, Cr vary between 20.35 and 12.18 indicating
      that the sediments have been contaminated with these metals in the reference
      point. Maximum enrichment factor values for Cr, Cu, Zn, Ba, Sr, Ni, Co vary
      between 22.91 and 11.42, implying that the sediments in hydrothermal area have
      been contaminated with these metals.

PMID- 22370649
TI  - A land surface 14C transfer model and numerical experiments on belowground 14C
      accumulation and its impact on vegetation 14C level.
AB  - A model simulating transport and exchange for 14C (or 14CO2) in a land surface
      ecosystem was developed and the belowground 14C accumulation and its impact on
      vegetation 14C accumulation at a hypothetical cultivated field were studied with
      the model through numerical experiments. The developed model involved physical
      14CO2 transport in surface atmosphere and soil and physiological 14CO2 exchanges
      in leaves, and was incorporated into a dynamical model (SOLVEG-II) that
      calculates transport and exchange for heat, water and CO2. The model was tested
      through a simulation of an existing-experiment on an acute exposure of grape
      plants to 14CO2. The calculated 14C amount in leaves agreed with the observations
      within a factor of 1.7. A hypothetical scenario used for the numerical
      experiments considered an annual 14C input into surface soil layers via 14C
      enriched foliage or root litter under a continually heightened atmospheric 14CO2
      concentration. The specific activity of 14C in the surface soil layers increased
      with time and several decades after the start of accumulation it eventually
      converged to eight times the initial specific activity. At this equilibrium
      state, the increased belowground 14CO2 production enhanced the atmospheric 14CO2
      level and, consequently, 14CO2 uptake by vegetation increased to 1.1 times the
      control calculated without belowground 14C accumulation. The model results also
      demonstrated that 14C accumulated in soil can maintain an enhanced vegetation 14C
      level for at least several decades even after the end of accumulation.

PMID- 22370650
TI  - Multivariate statistical analysis of radioactive variables in two phosphate ores
      from Sudan.
AB  - Multivariate statistical techniques are efficient ways to display complex
      relationships among many objects. An attempt was made to study the radioactive
      data in two types of Sudanese phosphate deposits; Kurun and Uro phosphate, using
      several multivariate statistical methods. Pearson correlation coefficient
      revealed that a U-238 distribution in Kurun phosphate is controlled by the
      variation of K-40 concentration, whereas in Uro phosphate it is controlled by the
      variation of U-235 and U-234 concentration. Histograms and normal Q-Q plots
      clearly show that the radioactive variables did not follow a normal distribution.
      This non-normality feature observed may be attributed to complicating influence
      of geological factors. The principal components analysis (PCA) gives a model of
      five components for representing the acquired data from Kurun phosphate, where
      89.5% of the total variance is explained. A model of four components was
      sufficient to represent the acquired data from Uro phosphate, where 87.5% of the
      total data variance is explained. The hierarchical cluster analysis (HCA)
      indicates that U-238 behaves in the same manner in the two types of phosphates;
      it associated with a group of four radionuclides; U-234, Po-210, Ra-226, Th-230,
      which the most abundant radionuclides, and all belong to the uranium-238 decay
      series. Two parameters have been adapted for the direct differentiate between the
      two phosphates. Firstly, U-238 in Uro phosphate have shown higher degree of
      mobility (CV% = 82.6) than that in Kurun phosphate (CV% = 64.7), and secondly,
      the activity ratio of Th-230/Th-232 in Uro phosphate is nine times than that in
      Kurun phosphate.

PMID- 22370651
TI  - Monitoring of radionuclides in soil and bone samples from Austria.
AB  - The activity concentrations of anthropogenic (90Sr, 137Cs) and natural (238U,
      232Th, 40K, 210Pb) radionuclides were determined in eight soil profiles from
      three different regions in Austria (Styria, Carinthia and Salzburg). A direct
      correlation between the activity concentration of 90Sr and 137Cs in soil samples
      and site altitude was found. 90Sr and 210Pb activity concentrations were also
      determined in bone ash of deer hunted in these regions. Additional bone samples
      were collected all over Austria. Totally 39 deer bones were investigated for this
      work, and some values were adopted from our earlier publications to give an
      overview of samples collected from sites covering a broad range of altitudes. The
      bone and soil samples were collected in the time period of 2001-2009. The 90Sr
      values in deer bones are directly proportional to the values in the respective
      soil samples and also to the age of the animals. For the 90Sr and 210Pb
      determinations in bone samples first Pb was separated on a Dowex column, then Sr
      was purified using Sr.Spec(r) resin. In soil samples an additional hydroxide
      precipitation was employed to eliminate interfering iron. For the first time also
      the 3M Empore(r) Sr Rad disk method was successfully applied to bone samples.
      With this method the chemical procedure can be shortened by more than a factor of
      2. The 90Sr and 210Pb fractions were measured by liquid scintillation counting,
      while the chemical yields were determined by ICP-MS. The activity concentrations
      of 40K, 238U, 232Th and 137Cs in soil samples were evaluated using gamma-ray
      spectrometry. The investigation was part of the PhD work of the first author.

PMID- 22370652
TI  - Multifractal structure of the 137Cs fallout at small spatial scales.
AB  - Regardless of the surface area of the site, the spatial distribution of
      radioactive contamination of soils with 137Cs for Chernobyl fallout is described
      by a lognormal distribution. Moreover, the spatial pattern of the radioactive
      contamination of soil is random geometrical multifractal field. Due to that, any
      contamination spot, when studied in detail, decomposes into a multitude of small
      spots decomposing further into a multitude of smaller spots etc. Similar patterns
      are apparently characteristic for fallout of other radionuclides, the Fukushima
      fallout, as well as atmospheric fallout of non-radioactive dust and aerosols.

PMID- 22370653
TI  - Modelling of the natural chlorine cycling in a coniferous stand: implications for
      chlorine-36 behaviour in a contaminated forest environment.
AB  - Considered as one of the most available radionuclide in soil-plant system, 36Cl
      is of potential concern for long-term management of radioactive wastes, due to
      its high mobility and its long half-life. To evaluate the risk of dispersion and
      accumulation of 36Cl in the biosphere as a consequence of a potential
      contamination, there is a need for an appropriate understanding of the chlorine
      cycling dynamics in the ecosystems. To date, a small number of studies have
      investigated the chlorine transfer in the ecosystem including the transformation
      of chloride to organic chlorine but, to our knowledge, none have modelled this
      cycle. In this study, a model involving inorganic as well as organic pools in
      soils has been developed and parameterised to describe the biogeochemical fate of
      chlorine in a pine forest. The model has been evaluated for stable chlorine by
      performing a range of sensitivity analyses and by comparing the simulated to the
      observed values. Finally a range of contamination scenarios, which differ in
      terms of external supply, exposure time and source, has been simulated to
      estimate the possible accumulation of 36Cl within the different compartments of
      the coniferous stand. The sensitivity study supports the relevancy of the model
      and its compartments, and has highlighted the chlorine transfers affecting the
      most the residence time of chlorine in the stand. Compared to observations, the
      model simulates realistic values for the chlorine content within the different
      forest compartments. For both atmospheric and underground contamination scenarios
      most of the chlorine can be found in its organic form in the soil. However, in
      case of an underground source, about two times less chlorine accumulates in the
      system and proportionally more chlorine leaves the system through drainage than
      through volatilisation.

PMID- 22370654
TI  - Ruptured renal artery aneurysm: coil packing with GDCs.
AB  - Renal artery aneurysm (RAA) is a relatively uncommon occurrence, but it can be
      life-threatening when rupture (although rare) occurs. We present the successful
      endovascular treatment of a ruptured RAA, which was achieved by packing the
      aneurysm using Guglielmi and interlocking detachable coils.

PMID- 22370655
TI  - The influence of ground contact and visible horizon on perception of distance and
      size under severely degraded vision.
AB  - For low vision navigation, misperceiving the locations of hazards can have
      serious consequences. Potential sources of such misperceptions are hazards that
      are not visually associated with the ground plane, thus, depriving the viewer of
      important perspective cues for egocentric distance. In Experiment 1, we assessed
      absolute distance and size judgments to targets on stands under degraded vision
      conditions. Normally sighted observers wore blur goggles that severely reduced
      acuity and contrast, and viewed targets placed on either detectable or
      undetectable stands. Participants in the detectable stand condition demonstrated
      accurate distance judgments, whereas participants in the undetectable stand
      condition overestimated target distances. Similarly, the perceived size of
      targets in the undetectable stand condition was judged to be significantly larger
      than in the detectable stand condition, suggesting a perceptual coupling of size
      and distance in conditions of degraded vision. In Experiment 2, we investigated
      size and implied distance perception of targets elevated above a visible horizon
      for individuals in an induced state of degraded vision. When participants' size
      judgments are inserted into the size-distance invariance hypothesis (SDIH)
      formula, distance to above-horizon objects increased compared to those below the
      horizon. Together, our results emphasize the importance of salient visible ground
      contact information for accurate distance perception. The absence of this ground
      contact information could be the source of perceptual errors leading to potential
      hazards for low vision individuals with severely degraded acuity and contrast
      sensitivity.

PMID- 22370656
TI  - Evaluation of soil contamination in intensive agricultural areas by pesticides
      and organic pollutants: south-eastern Spain as a case study.
AB  - A comprehensive survey of the occurrence and fate of pesticides and organic
      contaminants in soils from an intensive agricultural area devoted to
      horticultural production in plastic-based greenhouses has been performed to
      determine if the operation under integrated pest management practices has
      contributed to reduce the levels of these compounds. Almeria province (south
      eastern Spain) was selected for the case study. 38 agricultural soil samples
      (each sample corresponds to an independent private greenhouse) of areas working
      under integrated pest management (IPM) programs have been analyzed in order to
      evaluate their contamination fate. Sampling was designed to cover an area of
      about 400 km(2). Pesticides, polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), phenolic compounds and di-(2
      ethylhexyl)phthalate (DEHP) were monitored. The obtained results were compared to
      other studies reported in Spain and Europe. Among relevant persistent pesticides,
      DDTs and endosulfans were mainly found and the results indicated historical
      application, although recent application of endosulfan was rarely detected. PAHs
      were also found but to a lesser extent and derived from pyrogenic sources. DEHP
      levels were considerably higher in comparison to the other monitored analytes.
      The evaluation revealed that despite the use of IPM programs, pesticide and
      organic contaminants are still being detected in this type of agricultural soil,
      although at relatively low concentration levels. In general, the contamination
      rate was similar or lower in comparison to other agricultural areas from nearby
      regions or countries. However, further monitoring studies should be carried out
      to establish the possible reduction in contamination by the selected compounds.

PMID- 22370657
TI  - Treatment of retinal detachment associated with optic nerve head coloboma.

PMID- 22370658
TI  - Retinal vasoproliferative tumors in ocular conditions of childhood.
AB  - BACKGROUND: Retinal vasoproliferative tumor (RVPT) is a vascular mass with
      exudative retinopathy and minimally dilated feeder vessels. This type of tumor
      can occur as a primary or secondary condition. Our purpose was to describe
      secondary vasoproliferative tumors from ocular conditions in childhood. METHODS:
      The clinical records and fundus photographs of patients with secondary RVPTs were
      reviewed and a detailed literature search was conducted to identify reported
      cases of secondary RVPTs. This information was used to compile a list of ocular
      and nonocular childhood conditions associated with development of RVPTs. RESULTS:
      The ocular conditions related to vasoproliferative tumors in children include
      intermediate uveitis, retinitis pigmentosa, ocular toxocariasis, Coats disease,
      neurofibromatosis, retinal toxoplasmosis, retinopathy of prematurity, familial
      exudative vitreoretinopathy, and other rare conditions. CONCLUSIONS: Several
      pediatric ocular conditions can ultimately lead to retinal vasoproliferative
      tumor.

PMID- 22370659
TI  - Iris melanoma: features and prognosis in 317 children and adults.
AB  - PURPOSE: To evaluate iris melanoma in children versus adults. METHODS:
      Retrospective, nonrandomized clinical case series including all patients with a
      clinical diagnosis of iris melanoma managed at the Ocular Oncology Service at
      Wills Eye Institute over 40 years. Patients were divided into three age
      categories based on age at presentation: children (<= 20 years), mid-adults (21
      60 years), and older adults (>60 years). The clinical features, treatments, and
      outcomes were statistically analyzed based on patient age at presentation. The
      main outcome measures were melanoma features and related metastasis and death.
      RESULTS: Of 8,101 eyes with uveal melanoma, there were 317 (4%) with iris
      melanoma, including 24 (8%) children (<= 20 years), 187 (59%) mid-adults (21-60
      years), and 106 (33%) older adults (>60 years). There was no age-related
      difference in race, sex, tumor quadrant, thickness, pigmentation, associated
      corectopia, ectropion uveae, hyphema, or extraocular extension. Significant age
      related differences were found with mean tumor basal diameter, tapioca
      appearance, mean intraocular pressure, secondary glaucoma, tumor seeding in
      angle, and mean number of clock hours of angle seeding. Multivariate analysis of
      factors predictive of metastasis included extraocular extension and high
      intraocular pressure. Factors predictive of death included increased tumor
      thickness and high intraocular pressure. There was no difference in metastasis or
      death by age group. CONCLUSIONS: Iris melanoma shows significant clinical
      differences in children versus adults, with smaller tumor size, less tumor
      seeding in angle, and lower incidence of secondary glaucoma. There was no
      significant difference in metastasis or death by age group.

PMID- 22370660
TI  - The effect of surgical treatment of superior oblique muscle palsy on ocular
      torsion.
AB  - PURPOSE: To compare the effectiveness of superior oblique tuck and inferior
      oblique weakening procedures on objective and subjective torsion in patients with
      superior oblique palsy. METHODS: Patients with unilateral superior oblique palsy
      evaluated between September 2007 and October 2009 were treated with one of four
      surgical procedures on the basis of their preoperative findings: superior oblique
      tuck, anterior transposition of the inferior oblique muscle, inferior oblique
      recession, or inferior oblique myectomy. Subjective (double Maddox rods) and
      objective (fundus photography) torsion were measured pre- and postoperatively.
      RESULTS: A total of 28 patients were evaluated (mean age, 16.4 +/- 12.4 years;
      range, 6-51 years). In 15 (53.6%) the superior oblique palsy was congenital; in
      13 (46.4%) it was acquired. The mean decrease in subjective extorsion was 6.2
      degrees  +/- 2.3 degrees  after superior oblique tuck, 2.3 degrees  +/- 2.4
      degrees  after anterior transposition of the inferior oblique, 1.3 degrees  +/-
      2.7 degrees  after inferior oblique recession, and 2.6 degrees  +/- 4.7 degrees 
      after inferior oblique myectomy. Objective extorsion decreased by 5.8 degrees  +/
      0.8 degrees , 4.4 degrees  +/- 1.7 degrees , 3.1 degrees  +/- 3.2 degrees , and
      3.4 degrees  +/- 4.7 degrees , respectively. CONCLUSIONS: Superior oblique tuck
      appears to correct extorsion more effectively than inferior oblique surgery, but
      this may be an artifact of performing tucks in patients with greater initial
      extorsion. The small amount of extorsion correction was similar for all inferior
      oblique procedures.

PMID- 22370661
TI  - Inferior oblique muscle recession with and without superior oblique tendon tuck
      for treatment of unilateral congenital superior oblique palsy.
AB  - PURPOSE: To compare the surgical results in patients with congenital superior
      oblique palsy treated with inferior oblique recession (IOR) versus those treated
      additionally with superior oblique tendon tuck (IOR+SOT). METHODS: A consecutive,
      nonrandomized series of patients with congenital superior oblique palsy with
      vertical deviations in adduction between 10 degrees  and 20 degrees  were
      retrospectively reviewed. In the first series, patients were treated with IOR; in
      the second series, patients were treated with IOR+SOT. We examined the effects of
      surgery on binocular alignment and on the field of binocular single vision.
      RESULTS: Each group consisted of 20 patients. Preoperative ocular deviations were
      similar in both groups. Postoperative residual vertical deviations were not
      different in the primary position or in downgaze; however, significantly better
      alignment was achieved in the IOR+SOT group in adduction and downgaze in
      adduction. Consecutive Brown pattern occurred in 18 of 20 patients who underwent
      IOR+SOT versus 5 of 20 who underwent IOR. Residual torsion was not statistically
      different. The field of binocular single vision improved to 92% (range, 28%-100%)
      after IOR and to 96% (range, 64%-100%) after IOR+SOT (P = 0.20). CONCLUSIONS: IOR
      alone is a suitable procedure for most congenital superior oblique palsies with a
      moderate-to-large vertical deviation in adduction, resulting in a lower incidence
      of consecutive Brown pattern than with IOR+SOT.

PMID- 22370662
TI  - Long-term results of esotropia surgery in children with developmental delay.
AB  - PURPOSE: To assess the long-term results of esotropia surgery in children with
      developmental delay who were operated on with reduced surgical dosages. METHODS:
      This was a retrospective analysis of children with developmental delay who had
      undergone surgery for esotropia during a 16-year period. The pre- and
      postoperative angle of deviation was calculated for each subject as the mean of
      distant and near angles measured by a cover test or the Krimsky measurement. The
      main outcome measure was surgical success, categorized as esotropia or exotropia
      of <= 10(Delta). RESULTS: The chart review identified 24 children who met
      inclusion criteria, with a mean age of 2.8 +/- 2.5 years (range, 0.8-10 years).
      The mean angle of preoperative esotropia was 49.8(Delta) +/- 13.3(Delta). All
      patients had bilateral medial rectus muscle recessions, with a mean surgical
      dosage of 5.1 +/- 0.7 mm per muscle, on average 0.75 mm less than the standard
      amount. The average postoperative follow-up was 5.3 +/- 3 years (range, 1-13
      years). Surgical success was achieved in 9 of 24 children (37.5%) after one
      operation. Among the 15 failures, 10 (66.6%) were undercorrected, and 5 (33.3%)
      developed consecutive exotropia. Of these, 8 (53%) agreed to a second procedure.
      The overall surgical success rate for all patients after all procedures was 63%.
      CONCLUSIONS: Although the initial success rate is low with reduced surgical
      amounts in children with developmental delays, and some children become exotropic
      on long-term follow-up, satisfactory results may be achieved with additional
      procedures.

PMID- 22370663
TI  - Improved visual acuity and recognition time in nystagmus patients following four
      muscle recession or Kestenbaum-Anderson procedures.
AB  - PURPOSE: Many patients describe more rapid recognition of objects after surgical
      procedures for nystagmus; however, this "recognition time" is not reflected in
      the parameters typically studied in these patients. The purpose of this study is
      to assess the effect of nystagmus surgery on visual acuity and recognition time.
      METHODS: In this prospective, interventional, comparative case series, patients
      with nystagmus were divided into two groups. group A (n = 13) underwent four
      muscle retroequatorial recession; group B (n = 8) underwent the Kestenbaum
      Anderson procedure. Visual acuity, binocularity, and recognition time were
      assessed before and after surgery. Recognition time was measured in a routine
      examination setting using specially designed software that controlled the time of
      appearance of optotypes in 0.1 second increments. RESULTS: A total of 21 patients
      were enrolled. The entire group experienced significant postoperative improvement
      in visual acuity (P = 0.002) and recognition time (P = 0.005). The mean
      improvement in recognition time was 0.3 seconds at maximum preoperative visual
      acuity level. A trend toward more improvement in group A than in group B was not
      statistically significant. CONCLUSIONS: Both the four-muscle recession and the
      Kestenbaum-Anderson procedures resulted in a 1- to 2-line improvement in visual
      acuity and a 0.3 second improvement in optotype recognition time.

PMID- 22370664
TI  - Visual acuity deficits in the fellow eyes of children with unilateral amblyopia.
AB  - PURPOSE: To study the visual acuity deficits and maturation in the fellow eyes of
      children with unilateral amblyopia who were treated with patching. METHODS:
      Medical records of patients aged 4-13 years visiting a tertiary eye care center
      between January 2003 and December 2007 who were diagnosed for the first time with
      unilateral amblyopia were reviewed. Subjects included in the study were followed
      through April 2009. The baseline visual acuity in the fellow eye of amblyopic
      subjects was compared with that of age-matched healthy subjects. Changes in
      visual acuity in the amblyopic and fellow eyes during subsequent visits were
      analyzed. RESULTS: A total of 112 children with amblyopia were included
      (strabismic, 14; anisometropic, 51; combined mechanism, 47). Baseline visual
      acuity in the fellow eye of these children differed significantly from that of
      age-matched controls up to 8 years of age. Average logMAR acuity reached 0.0 at
      age 5 years in controls versus age 9 years in patients. Although the mean visual
      acuity of the fellow eyes improved during treatment, 21% developed temporary
      occlusion amblyopia. Full-time patching had no additional benefit when compared
      with part-time patching. CONCLUSIONS: Visual acuity in the fellow eye of children
      with unilateral amblyopia is reduced at baseline and matures more slowly than in
      healthy control patients. The risk for temporary occlusion amblyopia in the
      fellow eye is similar what has been previously reported.

PMID- 22370665
TI  - The relationship of axial length to cycloplegic refraction and keratometry in
      amblyopic eyes of hyperopic children.
AB  - BACKGROUND: In nonamblyopic eyes of hyperopic children, axial length has a
      consistent mathematical relationship to cycloplegic refraction and keratometry
      such that estimated axial length = ([-0.04 * refraction] + 2.98) * (corneal
      radius)]. The purpose of this study is to determine whether the pathophysiology
      of amblyopia affects this relationship. METHODS: This a prospective case series
      of children 5 to 16 years of age diagnosed with esotropia related to uncorrected
      hyperopia who underwent keratometry and optical biometry by the IOLMaster in
      addition to cycloplegic refraction. The equation was assessed in affected eyes of
      consecutive children with unilateral amblyopia (at least 2 lines interocular
      difference with refractive correction). RESULTS: Of the 23 identified children
      (16 males, 7 females, 5-14 years of age), all had a cycloplegic spherical
      equivalent of >=+2.75 D in at least one eye, 14 were anisometropic (by >1.00 D),
      and none had myopia. Estimated and measured axial lengths of amblyopic eyes were
      strongly correlated (Pearson coefficient 0.9; 95% confidence interval, 0.79-0.96)
      and did not differ significantly by the 2-sided paired t test (P = 0.3;
      difference between means, 0.1). The two values differed by <= 0.5 mm for most
      eyes (20/23) and were within 0.9 mm for all eyes, similar to what has been
      described for nonamblyopic eyes. CONCLUSIONS: The intraocular relationship of
      axial length to cycloplegic refraction and keratometry in hyperopic nonamblyopic
      eyes is maintained in hyperopic amblyopic eyes. Thus, the pathophysiology of
      amblyopia in this setting does not involve a mismatch among these biometric
      variables.

PMID- 22370666
TI  - Evaluation of treatment modalities and prognostic factors in children with
      congenital nasolacrimal duct obstruction.
AB  - PURPOSE: To evaluate the success rates of probing and silicone intubation and
      risk factors for failure of these procedures. METHODS: This retrospective cohort
      study included patients who were diagnosed with congenital nasolacrimal duct
      obstruction (NLDO) and underwent probing or intubation as the primary procedure.
      Demographic data, clinical features, intraoperative, and postoperative data were
      evaluated. The patients were divided into four subgroups based on age: 12-24
      months, 25-36 months, 37-48 months, and >48 months. The procedure was considered
      successful when all preoperative signs disappeared with normal dye disappearance
      test and a positive Jones primary dye test. Statistical analysis was performed to
      determine the risk factors for failure, and P < 0.05 was statistically
      significant. RESULTS: The cohort comprised 350 subjects (162 males [46%]) who
      underwent a total of 454 nasolacrimal duct surgeries. The mean chronological age
      at time of surgery was 32.6 +/- 22.1 months (range, 12-132 months). The overall
      success rate was 84.8%. Probing was performed 188 times, with a success rate of
      80.3%; intubation was performed 266 times, with a success rate of 88%.
      CONCLUSIONS: Intubation was more successful than probing in patients with
      bilateral congenital nasolacrimal duct obstruction, Down syndrome, history of
      acute dacryocystitis, lack of preoperative massage, or intraoperative observation
      of either a "tight" obstruction or obstruction at sites other than at the level
      of Hasner's valve. Primary nasolacrimal duct intubation should be considered in
      these higher risk patients.

PMID- 22370667
TI  - Home assessment of diurnal intraocular pressure in healthy children using the
      Icare rebound tonometer.
AB  - BACKGROUND: Although intraocular pressure (IOP) is known to vary with the
      circadian cycle in nonglaucomatous and glaucomatous eyes of adults, the clinical
      assessment of IOP often relies on periodic measurements obtained at office visits
      during daytime hours. Little has been reported on diurnal IOP patterns in healthy
      children. The purpose of this study was to evaluate diurnal IOP in normal eyes of
      healthy children with the Icare rebound tonometer and when recorded by a parent
      at home. METHODS: This was a prospective study of IOP in normal eyes of healthy
      children. Children were recruited from a pediatric eye clinic. A parent was
      instructed on the use of the Icare rebound tonometer by a study physician and
      demonstrated proficiency its use in the clinic, at which time a masked IOP
      reading was also made with Goldmann applanation by a different study clinician.
      Home IOPs were then obtained and recorded 6 times daily at 2- to 3-hours
      intervals during 2 consecutive days by a parent. RESULTS: A total of 22 normal
      eyes (of 11 children) were included. We found that children without glaucoma
      demonstrate mean diurnal IOP fluctuation of 4-6 mm Hg, with similar IOP between
      right and left eyes, fair repeatability between consecutive days, and a tendency
      for higher early morning and lower late evening IOP. CONCLUSIONS: Healthy
      children without glaucoma demonstrate some diurnal fluctuation in IOP, comparable
      with that reported in nonglaucomatous eyes of adults. This information should
      prove as comparative for assessment of IOP fluctuation in children with known or
      suspected glaucoma.

PMID- 22370668
TI  - The role of episcleral venous pressure in glaucoma associated with Sturge-Weber
      syndrome.
AB  - PURPOSE: To evaluate the role of episcleral venous pressure (EVP) in the
      pathogenesis of glaucoma associated with Sturge-Weber syndrome (SWS). METHODS:
      EVPs were determined prospectively using an episcleral venomanometer in 22 eyes
      of 11 patients aged 8-18 years with SWS with or without glaucoma. Pressure
      measurements in the glaucomatous eyes of patients with SWS were compared to those
      of patients with facial port wine marks but no glaucoma and to the contralateral
      uninvolved eye in both groups. RESULTS: EVP in eyes with glaucoma (mean, 20.9 mm
      Hg) was significantly higher (P < 0.01) than EVP in contralateral uninvolved eyes
      (mean, 9.6 mm Hg). In patients with unilateral port wine mark and no glaucoma,
      EVP was normal for ipsilateral and contralateral eyes (mean, 8.6 mm Hg and 9.6 mm
      Hg, respectively). CONCLUSIONS: Our data support the hypothesis that elevated EVP
      plays an important role in eyes with SWS glaucoma.

PMID- 22370669
TI  - Effect of the oxygen saturation target on clinical characteristics of early-
      versus late-onset retinopathy of prematurity.
AB  - PURPOSE: To investigate the relationship between postmenstrual age of onset of
      retinopathy of prematurity (ROP) and the need for treatment, while examining the
      effects of two different neonatal oxygen saturation protocols on this
      relationship. METHODS: A retrospective chart review was conducted for eligible
      inborn infants born before and after the institution of a new oxygen protocol
      adjusting target oxygen saturation from 90%-99% to 85%-93%. Early versus late
      onset ROP was defined as first presence of any stage disease on examination at
      <36 versus >= 36 weeks' postmenstrual age, respectively. RESULTS: The median
      birth weight/postmentrual age of infants was 840 g per 26.1 weeks (early-onset
      ROP) versus 952.5 g per 28 weeks (late-onset ROP; P < 0.01 vs P < 0.01). ROP
      developed in 119 of 369 (32.2%) of high oxygen target infants, and 100 of 373
      (26.8%) infants in the low-target group (P = 0.11). Cumulatively, 35 of 144
      (24.3%) of early-onset and 8 of 69 (11.6%) of late-onset patients required
      treatment (P = 0.03). Maximal severity of disease after treatment, including
      retinal detachment frequency, was similar in early- and late-onset patients,
      independent of the oxygen protocol (P = 1.00). CONCLUSIONS: The clinical behavior
      of type 1 ROP is similar in early-and late-onset disease, regardless of oxygen
      saturation targets. Type 1 ROP disease occurred in 11.6% of patients with late
      onset ROP.

PMID- 22370670
TI  - Competency checklists for strabismus surgery and retinopathy of prematurity
      examination.
AB  - PURPOSE: To evaluate two checklist tools that are designed to guide, document,
      and assess resident training in strabismus surgery and examination of infants at
      risk for retinopathy of prematurity (ROP). METHODS: A panel of staff surgeons
      from several teaching institutions evaluated the checklists and provided
      constructive feedback. All former residents who had been trained via the use of
      these checklist tools were asked to take self-assessment surveys on competency in
      strabismus surgery and ROP examination. A Likert 5-point scale was used for all
      evaluations, with 1 being the lowest rating and 5 the highest rating. RESULTS:
      Six experts in strabismus and seven in ROP rated the checklists. Their comments
      were used to revise the checklists, which were sent to the same group for
      reevaluation. The mean Likert score for the final checklists was 4.9 of 5.0 for
      both checklists. Of 16 former residents, 9 responded to the self-assessments with
      a mean overall score of 4.1 (of 5.0) for strabismus surgery and 3.9 for ROP
      examination. CONCLUSIONS: These checklist tools can be used to assess the quality
      of a resident's training and experience in these specific ophthalmology skills.
      They are complementary to other curriculum and assessment tools and can serve to
      organize the educational experience while ensuring a uniformity of training.

PMID- 22370671
TI  - A preequatorial Gore-Tex sling to restore rectus muscle pathways in myopic
      strabismus fixus.
AB  - A 74-year-old woman with high myopia presented with a rapid-onset, large-angle
      esotropia consistent with myopic strabismus fixus, or fallen eye syndrome. We
      treated the patient with combined bilateral disinsertion of the medial rectus
      muscles and resection of the right lateral rectus muscle with bilateral
      repositioning of the displaced superior and lateral rectus muscles toward their
      normal anatomic positions using a polytetrafluoroethylene (Gore-Tex) sling. The
      eyes were held in the orthotropic position for 7 days after surgery using nylon
      traction sutures. After 7 months of follow-up, the patient remained orthotropic
      at distance with a residual esotropia of 12(Delta) at near and a persistent
      limitation of elevation.

PMID- 22370672
TI  - Transient pseudo-Duane syndrome after lateral orbital trauma.
AB  - Duane syndrome is a dysinnervation disorder that frequently involves secondary
      anomalous eye movement, in particular, ocular retraction and the narrowing of the
      palpebral fissure on the adduction. Pseudo-Duane syndrome is caused by a
      mechanical restriction that produces clinical findings similar to those of Duane
      syndrome. Most patients with pseudo-Duane syndrome have restrictive pathologies
      on the medial side of the globe, such as entrapment of the medial rectus muscle.
      We report the case of a 44-year-old man with pseudo-Duane syndrome in whom we
      identified a lateral orbital wall fracture and entrapment of the soft tissue
      surrounding the lateral rectus muscle by computed tomography. To the best of our
      knowledge, this etiology of pseudo-Duane syndrome has not been previously
      reported.

PMID- 22370674
TI  - Myopia associated with optic nerve gliomas in neurofibromatosis type 1.
AB  - Optic nerve gliomas occur with increased frequency in neurofibromatosis type 1
      (NF1) and constitute NF1's most frequent cause of visual loss. Axial elongation
      of the globe may occur in NF1 as a consequence of glaucoma, but in the absence of
      glaucoma that occurrence has received limited attention. We present 4 patients
      with NF1 who were found to have myopia and anisometropia in association with
      unilateral or asymmetric optic nerve gliomas. In one patient, progressive
      enlargement of the optic nerve glioma corresponded with further increases in
      myopia. To our knowledge, the association of myopia ipsilateral to the presence
      or growth of optic nerve gliomas has not been reported.

PMID- 22370673
TI  - Measurement of retinal nerve fiber layer thickness, macular thickness, and foveal
      volume in amblyopic eyes using spectral-domain optical coherence tomography.
AB  - Although the changes in the anatomy of the visual cortex and lateral geniculate
      nucleus as the result of amblyopia have been well documented, retinal involvement
      is still controversial. Time-domain optical coherence tomography with an axial
      resolution of 10 MUm has been used to evaluate retinal and peripapillary tissues
      in amblyopic eyes with contradictory results. Spectral domain optical coherence
      tomography has a greater resolution (5-10 MUm) and can determine retinal layers
      more precisely. Our purpose was assess by means of spectral domain optical
      coherence tomography whether the retinal nerve fiber layer thickness, macular
      thickness, and foveal volume of the amblyopic and the fellow eyes differ in
      patients with unilateral amblyopia. Intereye differences in these parameters were
      found to be insignificant.

PMID- 22370675
TI  - Long-term follow-up after bilateral Artisan aphakia intraocular lens implantation
      in two children with Marfan syndrome.
AB  - We present two patients with Marfan syndrome and bilateral crystalline lens
      dislocation who underwent bilateral lens extraction and Artisan aphakia
      intraocular lens (IOL) implantation. With a follow-up of more than 12 years, we
      found a good visual outcome, no serious IOL-related complications, and
      endothelial cell densities within the expected range for eyes without cataract
      surgery.

PMID- 22370676
TI  - Treatment of recurrent retinal detachment secondary to optic nerve coloboma with
      injection of autologous platelet concentrate.
AB  - A 14-year-old girl presented with a recurrent retinal detachment secondary to
      optic nerve coloboma in her left eye with a small retinal hole in the bed of the
      coloboma, confirmed by optical coherence tomography. The patient was treated by
      injection of 0.05 mL of autologous platelet concentrate into the coloboma along
      with vitrectomy and gas exchange. After 8 months, the retina was attached and
      optical coherence tomography revealed closure of the retinal hole. Considering
      our experience, autologous platelet injection may be considered a treatment
      option for recurrent retinal detachment secondary to optic nerve coloboma.

PMID- 22370677
TI  - Reduction of thrombus size in murine models of thrombosis following
      administration of recombinant alpha1-proteinase inhibitor mutant proteins.
AB  - The variant serpin alpha1-PI M358R inhibits thrombin and other proteases such as
      activated protein C (APC) and factor XIa. We previously described recombinant
      proteins HAPI M358R (alpha1-PI M358R containing an N-terminal extension
      corresponding to residues 1-75 of heparin cofactor II) and HAPI RCL5 (HAPI M358R
      with F352-I356 and I360 substituted for the corresponding residues of
      antithrombin), with enhanced selectivity for thrombin over APC inhibition. We
      tested the hypotheses that these recombinant proteins would limit thrombosis in
      three mouse models, and that the HAPI chimeric proteins would be more effective
      than alpha1-PI M358R. Recombinant serpins were purified from  Escherichia coli 
      by nickel chelate and ion exchange affinity chromatography, and administered to
      mice intravenously. HAPI RCL5 reduced incorporation of radiolabelled fibrin(ogen)
      into thrombi in the ferric chloride-injured vena cava in a dose-dependent manner;
      HAPI M358R was less effective and alpha1-PI M358R was without effect. In a model
      of murine endotoxaemia, HAPI RCL5 was more effective than alpha1-PI M358R in
      reducing radiolabelled fibrin(ogen) deposition in heart and kidneys;
      immunohistochemistry of tissue sections showed lesser staining with anti
      fibrin(ogen) antibodies with both treatments. In the ferric chloride-injured
      murine carotid artery, administration of both recombinant serpins was equally
      effective in lengthening the vessel's time to occlusion. Our results show that
      the antithrombotic efficacy of the recombinant serpins correlates with their
      potency as thrombin inhibitors, since HAPI RCL5 inhibits thrombin, but not
      factors Xa, XIa, XIIa, or neutrophil elastase, more rapidly than alpha1-PI M358R.

PMID- 22370678
TI  - Utility of the Seattle heart failure model in stratification of heart failure
      patients for ventricular assist device therapy.

PMID- 22370679
TI  - Comparison of observed survival after ventricular assist device placement versus
      predicted survival without assist device using the Seattle heart failure model.
AB  - Determining optimal timing for implant of ventricular assist device (VAD) in end
      stage heart failure remains a challenge and may be aided by a risk assessment
      tool. For a cohort of 80 consecutive VAD implants at a single center, observed 1
      year survival post-VAD was compared with the estimated survival had these
      patients not received a VAD, using the Seattle Heart Failure Model (SHFM). The
      SHFM was adjusted with a hazard ratio of 1.17 for inotrope use (Cochrane Meta
      analysis of phosphodiesterase inhibitors) and a hazard ratio of 2.92 for balloon
      pump, ventilator, or renal replacement therapy (Comparative Outcome and Clinical
      Profiles in Transplantation [COCPIT] Model). Values immediately before surgery
      were used to calculate the SHFM score. Point estimates of 1 year survival were
      compared using Z scores. Mean age was 53 +/- 14 (+/- standard deviation [SD])
      years with mean left ventricular ejection fraction of 17 +/- 6%. At the time of
      VAD implant, 92% were on inotropes, 53% had balloon pump, and 15% were intubated.
      For the entire cohort, 1 year survival without VAD predicted by the SHFM was 47%
      versus observed survival after VAD of 60% (p = 0.06). The model was most helpful
      in patients electively implanted with a left ventricular assist device (LVAD). In
      this group predicted 1 year survival on medical management was 49% versus an
      observed survival of 82% after LVAD placement (p < 0.05). The model was least
      helpful in patients undergoing placement of biventricular assist devices (BiVAD),
      where the model paradoxically predicted better survival with ongoing medical
      management. This indicated that the model was unable to forecast outcome in
      patients with higher severity of illness, for example, in cases warranting BiVAD
      placement. Observed 1 year survival was better with VAD versus that predicted
      with medical management. Tools such as the SHFM may aid in determining
      appropriate timing for VAD by providing an estimated survival with ongoing
      medical management. The model is best applied to more stable patients being
      considered for elective VAD implantation.

PMID- 22370680
TI  - Artificial muscle for end-stage heart failure.
AB  - We describe a device made of artificial muscle for the treatment of end-stage
      heart failure as an alternative to current heart assist devices. The key
      component is a matrix of nitinol wires and aramidic fibers called Biometal muscle
      (BM). When heated electrically, it produces a motorless, smooth, and lifelike
      motion. The BM is connected to a carbon fiber scaffold, tightening the heart and
      providing simultaneous assistance to the left and right ventricles. A pacemaker
      like microprocessor drives the contraction of the BM. We tested the device in a
      dedicated bench model of diseased heart. It generated a systolic pressure of 75
      mm Hg and ejected a maximum of 330 ml/min, with an ejection fraction of 12%. The
      device required a power supply of 6 V, 250 mA. This could be the beginning of an
      era in which BMs integrate or replace the mechanical function of natural muscles.

PMID- 22370681
TI  - Real-time continuous neuromonitoring combines transcranial cerebral Doppler with
      near-infrared spectroscopy cerebral oxygen saturation during total aortic arch
      replacement procedure:  a pilot study.
AB  - The purpose of this investigation was to use combined transcranial cerebral
      Doppler (TCD) and near-infrared spectroscopy cerebral oxygen saturation (NIRS)
      during total aortic arch replacement (TAAR) to monitor middle cerebral artery
      blood flow velocity and regional cerebral oximetry (rSO(2)) changes to provide a
      clinical basis for protective measures that may decrease injury of the central
      nervous system. Consecutive 12 adult patients underwent deep hypothermic
      circulatory arrest (DHCA) and antegrade selective cerebral perfusion (ASCP)
      during TAAR. A TCD probe was placed at the temporal windows after induction of
      anesthesia and the NIRS probe placed on the forehead of patients to collect
      perioperative, intraoperative, and postoperative hemodynamic parameters, and
      cerebral blood flow (CBF) and rSO(2) during cardiopulmonary bypass (CPB). In this
      retrospective case series, all patients survived, and there were no postoperative
      neurologic complications. There was no significant correlation between the mean
      arterial pressure and rSO(2). The middle cerebral artery mean velocity (VmMCA)
      and rSO(2) were significantly correlated, and main pump flow significantly
      correlated with rSO(2). After ASCP, VmMCA, rSO(2), and venous oxygen saturation
      were significantly lower than before ASCP, but VmMCA and rSO(2) returned to pre
      CPB levels postoperatively. After off pump, the flow of ASCP showed a significant
      positive correlation with VmMCA and rSO(2). During DHCA when ASCP flow was lower
      than 5 ml/kg/min, TCD could not detect the MCA blood flow signal. When the flow
      of ASCP was above keeping around 10 ml/kg/min, MCA CBF velocity was maintained
      and rSO(2) > 45%. The combination of TCD and NIRS can be effective in monitoring
      brain function during DHCA with ASCP and may provide a guide for decreasing brain
      injury during the TAAR procedure.

PMID- 22370682
TI  - Dialysate purification after introduction of automated hot water disinfection
      system to central dialysis fluid delivery system.
AB  - Most dialysis clinics in Japan have mainly adopted the central dialysis fluid
      delivery system (CDDS) to provide constant treatment to many patients. Chemical
      disinfection is the major maintenance method of the CDDS. Our clinic introduced
      an automated hot water disinfection system that used the heat conduction effect
      to disinfect a reverse osmosis (RO) device and dialysis fluid supply equipment.
      Endotoxin level and the amount of viable bacteria often showed abnormal values
      before introduction of this system. After its introduction, weekly disinfection
      resulted in endotoxin levels and the amount of viable bacteria lower than
      measurement sensitivity. In hot water disinfection, water heated to 90 degrees C
      in the RO tank flows into the dialysis fluid supply equipment. The maximum
      temperature inside the tank of the supply equipment is 86.3 degrees C. (We
      confirmed that the temperature was maintained at 80 degrees C or more for 10
      minutes or more during the monitoring.) Dialysate purification was maintained
      even after introduction of the automated hot water disinfection system and the
      dialysate could be supplied stably by the CDDS. Therefore, this disinfection
      system might be very useful in terms of both cost and safety, and can be used for
      dialysis treatment of multiple patients.

PMID- 22370683
TI  - Fluid state and blood pressure control: no differences between APD and CAPD.
AB  - The aim of this study was to compare fluid state, ambulatory blood pressure, and
      sodium removal in automated peritoneal dialysis (APD) and continuous ambulatory
      peritoneal dialysis (CAPD). This observational, cross-sectional study comprised
      20 APD and 24 CAPD patients with a mean duration on peritoneal dialysis of 30 +/-
      26 and 21 +/- 23 months, respectively. Sixty-four percent of the patients were
      treated with icodextrin. The methods used were 24 hr dialysate and urine
      collections, standardized 3.86% glucose peritoneal equilibration test (PET),
      bioimpedance analysis, and 24 hr ambulatory blood pressure monitoring.
      Extracellular water (ECW) corrected for body weight was 0.23 6 0.03 L/kg both in
      APD and CAPD patients. The slope normovolemia value according to Chamney was 0.0
      6 0.2 L/kg in APD patients and 0.0 6 0.05 L/kg in CAPD patients (not significant
      [NS]). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were
      respectively, 132 +/- 25 and 79 +/- 8 mm Hg in APD and 129 +/- 16 and 76 +/- 11
      mm Hg in CAPD patients (NS). Sodium concentration in dialysate was respectively,
      129.5 +/- 3.5 mmol/L in APD and 132.4 +/- 4.1 mmol/L in CAPD (p= 0.017).
      Dialysate sodium removal was 80.6 +/- 78.4 mmol/24 hr in APD and 108.7 +/- 96.8
      mmol/24 hr in CAPD patients (NS). Natriuresis was respectively, in APD 76.6 +/-
      65.5 mmol/24 hr and in CAPD 93.5 +/- 61.7 mmol/24 hr (NS). Total sodium removal
      was 149.5 +/- 76.6 mmol/24 hr in APD and 198.4 +/- 75.0 mmol/24 hr in CAPD (p=
      .039). Despite a higher daily sodium removal in CAPD patients, fluid state and
      blood pressure were not different between APD and CAPD. In general, volume status
      and blood pressure appeared to be reasonably controlled in this unselected
      population.

PMID- 22370684
TI  - Abdominal compartment syndrome in newborns and children supported on
      extracorporeal membrane oxygenation.
AB  - The objective of this study was to investigate the effect of timely peritoneal
      dialysis (PD) catheter in children with abdominal compartment syndrome (ACS)
      while supported on extracorporeal membrane oxygenation (ECMO). We present a case
      series of four patients who developed significant intraperitoneal fluid
      accumulation and ACS at the general pediatric and cardiac intensive care units in
      a tertiary children's hospital. The hospital's ECMO database was queried for
      patients supported on ECMO who required PD catheter placement. These patients
      were assessed for clinical characteristics and outcomes. Four patients were
      identified with capillary leak syndrome associated with a primary diagnosis:
      cardiac transplant rejection in one, septic shock and acute respiratory distress
      syndrome in two, and neonatal hydrops fetalis in one patient. In each of these
      patients, a PD catheter was placed for severe abdominal distension and
      proven/suspected ACS. There was dramatic improvement in venous return after
      drainage of peritoneal fluid. Two patients were subsequently able to be separated
      successfully from ECMO support. One patient died of acute neurologic complication
      and the other because of severe gastrointestinal bleeding. After ruling out
      common causes for decreased venous return, ACS should be suspected as one of the
      important causes, especially in patients with massive capillary leak and
      increasing abdominal distension, among patients supported on ECMO. Timely
      placement of a PD catheter in patients who develop abdominal distension and ACS
      can substantially improve venous return and thus help maintain adequate tissue
      perfusion by improving ECMO flows.

PMID- 22370685
TI  - Development of an artificial placenta IV: 24 hour venovenous extracorporeal life
      support in premature lambs.
AB  - An extracorporeal artificial placenta would change the paradigm of treating
      extremely premature infants. We hypothesized that a venovenous extracorporeal
      life support (VV-ECLS) artificial placenta would maintain fetal circulation,
      hemodynamic stability, and adequate gas exchange for 24 hours. A near-term
      neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right
      jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used
      for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow
      fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up
      to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors,
      average mean arterial pressure was 69 +/- 10 mm Hg for the first 4 hours and 36
      +/- 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 +/- 30.
      Mean VV-ECLS flow was 94 +/- 20 ml/kg/min. Using a gas mixture of 50% O(2)/3%
      CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 +/- 0.09, with Po(2) of
      35 +/- 12 mm Hg and Pco(2) of 48 +/- 12 mm Hg. Necropsy revealed a patent ductus
      arteriosus in all cases, and there was no gross or microscopic intracranial
      hemorrhage. Complications in failed attempts included technically difficult
      cannulation and multisystem organ failure. Future studies will enhance stability
      and address the factors necessary for long-term support.

PMID- 22370686
TI  - Complete respiratory support with AVCO2R and CPAP-mimic ventilation for total gas
      exchange in sheep.
AB  - The altered respiratory mechanics in patients with chronic obstructive pulmonary
      disease (COPD) present unique challenges with regard to treatment during an acute
      exacerbation that often leads to respiratory support with mechanical ventilation.
      Alternative therapies are badly needed to reduce morbidity and mortality
      associated with mechanical ventilator use. We hypothesized that arteriovenous
      carbon dioxide removal (AVCO(2)R) coupled with continuous positive airway
      pressure (CPAP) would achieve total gas exchange eliminating the need for
      intubation/mechanical ventilation, thus reducing baro/volutrauma. This hypothesis
      was tested in six adult sedated apneic sheep with AVCO(2)R administered through a
      simple arteriovenous (AV) shunt for CO(2) removal. Because it is impractical to
      apply a CPAP mask to conscious sheep, the CPAP was mimicked in intubated/sedated
      sheep by positive end-expiratory pressure (PEEP) of 5-10 mmH(2)O with negligible
      ventilation. The AVCO(2)R and CPAP-mimic maintained Pa(o)(2) and Pa(co)(2) in the
      normal physiological ranges. The CO(2) removal was 120-150 ml/min through
      AVCO(2)R with AV blood flow of 1.1-1.5 L/min. A high fraction of inspired oxygen
      percentage (Fi(o)(2)) level (89 +/- 3%) was required to achieve 40 +/- 7% O(2) in
      the small bronchus. Thus, AVCO(2)R and CPAP-mimic achieved total gas exchange in
      anesthetized sheep and may be a potential option for acute COPD exacerbation in
      humans.

PMID- 22370687
TI  - Correction of plasma concentrations for effects of hemoconcentration or
      hemodilution.
AB  - The removal of plasma water during hemodialysis and ultrafiltration usually leads
      to a decrease in plasma volume and to a concomitant increase in the concentration
      of components not removed by that process. At a baseline hematocrit of 35% the
      relative change of a component measured per unit plasma volume is almost twice as
      large as the concomitant change in hematocrit or hemoglobin concentration
      measured per unit blood volume. Thus, to asses whether the change of a plasma
      component results from the volume change or from other aspects of the
      intervention, the plasma concentration measured per unit plasma volume has to be
      divided by the hemoconcentration for the plasma compartment h(p) = H(1) (100 -
      H(0))/(H(0)[100 - H(1)]), where H is the hematocrit in percent and where indices
      0 and 1 refer to the condition before and after intervention, and not by the
      hemoconcentration for the blood compartment h(H) = H(1)/H(0), as it is frequently
      done.

PMID- 22370688
TI  - von Willebrand factor, shear stress, and ADAMTS13 in hemostasis and thrombosis.
AB  - von Willebrand factor (VWF), an adhesive glycoprotein whose deficiency is best
      known for causing bleeding in patients with von Willebrand disease (VWD), is a
      complex molecule with a myriad of mysterious properties including its dependence
      on shear stress for adhesive functions. The discovery of ADAMTS13 has provided a
      critical impetus for understanding the regulation of VWF activity by shear
      stress. This communication reviews the current knowledge in VWF homeostasis and
      illustrates how this knowledge may help understand the changes affecting patients
      with various conditions including thrombotic thrombocytopenic purpura, VWD,
      hemolytic uremic syndrome, aortic stenosis, and ventricular assist devices.

PMID- 22370689
TI  - Ventricular fibrillation in an ambulatory patient supported by a left ventricular
      assist device: highlighting the ICD controversy.
AB  - Left ventricular assist devices (LVADs) provide an effective means of managing
      advanced pump failure as a means of bridging to cardiac transplantation or as
      permanent therapy. Although ventricular arrhythmias remain common post-LVAD
      implantation, such therapy may allow malignant arrhythmias to be tolerated
      hemodynamically. This report describes the clinical findings in a patient who had
      likely been in a ventricular tachyarrhythmia for several days and presented in
      ventricular fibrillation, ambulatory, and mentating normally. This report, with
      previous similar reports, is additive to the body of evidence that LVADs alter
      the physiologic impact of ventricular arrhythmias in advanced heart failure and
      highlights the need for thoughtful programming of implantable cardioverter
      defibrillator therapies in these patients.

PMID- 22370690
TI  - Successful living donor liver transplantation for fulminant hepatic failure that
      manifested immediately after cesarean delivery.
AB  - A 31-year-old pregnant woman was diagnosed as having acute hepatitis of unknown
      etiology and conservatively treated. An emergency cesarean delivery was performed
      5 days later at 33 weeks and 3 days of gestation because of a gradual
      deterioration in liver function. Two days after the cesarean delivery, she lost
      consciousness in the evening (Glasgow coma scale [GCS] = 9) because of hepatic
      encephalopathy and was diagnosed as having fulminant hepatic failure (FHF). Five
      days after the cesarean delivery, the patient (blood type B) underwent a
      successful left lobe with caudate lobe (S1+2+3+4) liver transplantation from her
      father (blood type AB), an ABO-incompatible donor. At 1 year follow-up, she and
      her baby are in good medical condition. The drastic deterioration in hepatic
      function, despite intensive plasmapheresis and continuous hemodiafiltration,
      during the early postpartum period suggested a possible causative association
      between the termination of pregnancy and progression of FHF from acute hepatitis
      of unknown etiology.

PMID- 22370691
TI  - Value of routine immediate postoperative brain computerized tomography in
      pediatric neurosurgical patients.
AB  - PURPOSE: Routine immediate postoperative brain CT (RIPO CT) has advantages and
      disadvantages. The present study was performed to know the extent of gain by RIPO
      CT in the aspect of immediate postoperative patient care in pediatric patient
      population and according to the disease entity and surgical procedure. METHODS:
      We reviewed 910 cases of pediatric brain surgery performed from January 2008 to
      March 2010 who had RIPO CT. The value of each examination was graded according to
      the impact of the CT findings on the decision making processes on postoperative
      patient care or on the understanding of postoperative patient's status: level I
      (urgent surgical procedures are necessary), level II (high level of attention
      should be paid because of possible urgent surgical procedure in near future),
      level III (RIPO CT is useful for understanding of postoperative change of
      patient's status), and level IV (no significant gain). The number of patients in
      each level was evaluated, and proportions of levels according to disease entity
      and surgical procedure were compared. RESULTS: In total, the proportion of each
      level of I to IV was 0.4%, 4.9%, 3.5%, and 91.2%, respectively. The group of
      brain tumors, especially those who have malignant or highly vascular tumors,
      showed significantly higher value of RIPO CT. Cases of traumatic epidural
      hematoma and intracerebral hemorrhage revealed significantly high proportion of
      level II although no case underwent reoperation. CONCLUSIONS: The results of
      present study may be useful for making policy of "selective" application of
      immediate postoperative brain CT according to the patient conditions. Also the
      use of immediate postoperative brain CT can be decided in individual cases by
      considering disease entity and surgical procedure.

PMID- 22370692
TI  - Localization and quantification of Pb and nutrients in Typha latifolia by micro
      PIXE.
AB  - Typha latifolia is a plant species widely used for phytoremediation.
      Accumulation, localization and distribution of Pb and mineral nutrients were
      investigated in roots, rhizomes and leaves of Typha latifolia grown at 0, 50, 100
      and 250 MUM Pb concentrations in a pot experiment under controlled conditions.
      Bulk elemental concentrations were determined by X-ray fluorescence (XRF)
      spectroscopy whereas micro-proton-induced X-ray emission (micro-PIXE) was used
      for element localization in root and rhizome tissues. Gradual increase in bulk Pb
      concentrations was observed in Typha latifolia roots and rhizomes treated with
      increasing Pb concentrations, however in rhizomes Pb concentrations were an order
      of magnitude lower than in roots. In leaves Pb concentrations were around the
      limit of detection for XRF (~20 MUg g(-1)). An increase in concentration of K and
      Ca in roots, rhizomes and leaves, of iron and zinc in roots and leaves, and of Mn
      in rhizomes was observed either at 50 and/or 100 MUM Pb treatments, whereas for K
      and Ca in roots, rhizomes and leaves, Fe and Zn in roots and leaves and Mn in
      rhizomes, or at 250 MUM Pb treatment the increase was seen for concentrations of
      Fe and Zn in rhizomes and Cu in roots. Mn concentrations decreased with Pb
      treatments in roots and leaves. Element localization using micro-PIXE analysis
      demonstrated Pb accumulation in epidermal and cortical tissues of treated roots
      and rhizomes, while in endodermis and vascular tissues Pb was not detected. A
      displacement of Ca from epidermal to cortical tissues was observed in Pb treated
      roots and rhizomes, pointing to cell wall immobilization of Pb as one of the
      tolerance mechanisms in Typha latifolia. High level of colocalization of Pb with
      P (r = 0.60), S (r = 0.37) and Zn (r = 0.70) was observed in Pb treated roots,
      while in rhizomes colocalization with the mentioned elements was still positive,
      but not that prominent. These results indicate that Pb may form complexes with
      phosphorus and sulfur compounds in roots and rhizomes, which may also represent
      attraction sites for binding Zn. Because of its large root and rhizome surface
      area acting as main sites for Pb adsorption, Typha latifolia may represent
      potentially efficient plant species for phytoremediation of Pb contaminated soils
      and waters.

PMID- 22370693
TI  - Clinical demand for chest/abdomen/pelvis anatomy following thoracic or lumbar
      spine CT.
AB  - The purpose of this study is to determine how often CT is repeated to obtain
      chest/abdomen/pelvis data outside the reconstructed field of view (FOV) on a
      prior spine CT. Radiology records of 1,239 consecutive thoracic and lumbar spine
      CT exams of 1,025 patients from January 1, 2006 to December 31, 2008 were
      retrospectively reviewed to identify patients who subsequently had CT studies of
      the chest, abdomen, and/or pelvis. The CT data were also evaluated for contrast
      enhancement, slice thickness, radiation dose, and reason for subsequent CT exam.
      Over 3 years, 290 of the 1,239 (24%) spine CT exams were followed by CT of the
      same anatomic region to evaluate extraspinal anatomy. The use or nonuse of
      contrast in these follow-up studies was the same as the preceding spine study in
      91 cases, which were repeated on the same day (n = 37), within 7 days (n = 19),
      within 8-30 days (n = 15), or after 30 days (n = 20). Fourteen of 25 (56%) T
      spine CTs and 34 of 52 (65%) L spine CTs without contrast were followed by a
      chest CT or abdomen/pelvis CT without contrast within 7 days, respectively. Among
      31 pediatric exams, 6 of 31 (19%) spine CTs were followed by a CT of the same
      anatomic region, all within 7 days. Reconstructing full FOV images of spine CT
      scans in addition to the standard coned down spine FOV may reduce redundant CT
      imaging and radiation dose.

PMID- 22370694
TI  - Utility of ultrasound for evaluating the appendix during the second and third
      trimester of pregnancy.
AB  - This study aims to retrospectively evaluate the right lower quadrant ultrasounds
      in women presenting during the second or third trimester of pregnancy for the
      frequency of appendix visualization and accuracy in diagnosing appendicitis.
      Institutional Review Board approval was obtained for this Health Insurance
      Portability and Accountability Act-compliant study. We reviewed imaging records
      from 99 consecutive pregnant women from 2001 to 2011 who presented during the
      second (>=14 weeks gestation) or third trimester for right lower quadrant
      ultrasound to evaluate the appendix. Visualization of the appendix as well as the
      size and compressibility, if identified, were recorded. The medical records and
      labs related to the initial patient presentation, subsequent management, and
      follow-up were reviewed for surgical and clinical outcomes. Pathology records
      were reviewed to determine if appendicitis was present when appendectomy was
      performed. Patients who underwent appendectomy were considered to have
      appendicitis based on pathology results, and patients managed non-operatively
      with symptom improvement and those with a normal appendix at pathology were
      considered to not have appendicitis. During the study period, 99 women meeting
      inclusion criteria presented to our institution for right lower quadrant
      ultrasound to evaluate the appendix during the second or third trimester of
      pregnancy. The mean gestational age at presentation was 23 weeks (+/-7 weeks).
      The mean maternal age was 28 years (+/-6.6 years). The appendix was not
      visualized in 97% (96/99) of right lower quadrant ultrasound examinations. Of the
      three studies in which the appendix was visualized, two were considered positive
      for appendicitis and one was considered negative. Eight patients in this group
      ultimately underwent appendectomy, including the two patients with positive right
      lower quadrant ultrasounds, and appendicitis confirmed at pathology in seven of
      these cases (87.5%). Right lower quadrant ultrasound successfully demonstrated an
      abnormal appendix in 28.7% (two of seven) of surgically confirmed cases; however,
      this technique did not detect appendicitis in 71% (five of seven) of patients
      with surgically proven disease due to nonvisualization of the appendix.
      Retrospective review of right lower quadrant ultrasounds performed during the
      second and third trimester of pregnancy suggests that this modality has limited
      utility for diagnosing appendicitis due to infrequent visualization of the
      appendix.

PMID- 22370695
TI  - Percutaneous transhepatic obliteration for massive variceal rectal bleeding.

PMID- 22370697
TI  - Internet use among childhood and young adult cancer survivors who smoke:
      implications for cessation interventions.
AB  - OBJECTIVE: To identify patterns of Internet use among childhood and young adult
      cancer survivors who smoke. METHODS: Baseline assessment data were collected from
      2005 to 2008 for the Partnership for Health-2 (PFH-2) study, a web-based smoking
      cessation intervention for childhood and young adult cancer survivors.
      Participants were surveyed about their Internet access and use. Sociodemographic,
      clinical, and psychosocial data also were collected. RESULTS: Internet access and
      use was widespread among PFH-2 participants. However, older, less-educated, and
      female survivors reported less frequent Internet use, even when they had access
      to the Internet at home and/or at work. These associations were significant in
      multivariable analyses. CONCLUSIONS: Although the digital divide is narrowing,
      Internet use and engagement remains socially patterned. web-based prevention
      interventions are a promising method of reaching this geographically dispersed,
      high-risk population, but certain subgroups-particularly older and lower
      socioeconomic status survivors-might be missed by this approach.

PMID- 22370696
TI  - The vector of the tobacco epidemic: tobacco industry practices in low and middle
      income countries.
AB  - PURPOSE: To understand transnational tobacco companies' (TTCs) practices in low
      and middle-income countries which serve to block tobacco-control policies and
      promote tobacco use. METHODS: Systematic review of published research on tobacco
      industry activities to promote tobacco use and oppose tobacco-control policies in
      low and middle-income countries. RESULTS: TTCs' strategies used in low and middle
      income countries followed four main themes-economic activity;
      marketing/promotion; political activity; and deceptive/manipulative activity.
      Economic activity, including foreign investment and smuggling, was used to enter
      new markets. Political activities included lobbying, offering voluntary self
      regulatory codes, and mounting corporate social responsibility campaigns.
      Deceptive activities included manipulation of science and use of third-party
      allies to oppose smoke-free policies, delay other tobacco-control policies, and
      maintain support of policymakers and the public for a pro-tobacco industry policy
      environment. TTCs used tactics for marketing, advertising, and promoting their
      brands that were tailored to specific market environments. These activities
      included direct and indirect tactis, targeting particular populations, and
      introducing new tobacco products designed to limit marketing restrictions and
      taxes, maintain the social acceptability of tobacco use, and counter tobacco
      control efforts. CONCLUSIONS: TTCs have used similar strategies in high-income
      countries as these being described in low and middle-income countries. As
      required by FCTC Article 5.3, to counter tobacco industry pressures and to
      implement effective tobacco-control policies, governments and health
      professionals in low and middle-income countries should fully understand TTCs
      practices and counter them.

PMID- 22370698
TI  - A randomized controlled trial of oral melatonin supplementation and breast cancer
      biomarkers.
AB  - We examined compliance with and the effects of melatonin supplementation on
      breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1),
      insulin-like growth factor-binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3
      ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo
      controlled study, postmenopausal women with a prior history of stages 0-III
      breast cancer who had completed active cancer treatment (including hormonal
      therapy) were randomly assigned to either 3 mg oral melatonin (n = 48) or placebo
      daily for 4 months. Plasma samples were collected at baseline and after the
      completion of the intervention. The primary endpoints were compliance and change
      in estradiol and IGF-1/IGFBP-3 levels. Ninety-five women were randomized (48 to
      melatonin and 47 to placebo). Eighty-six women (91%) completed the study and
      provided pre- and postintervention bloods. Melatonin was well tolerated without
      any grade 3/4 toxicity and compliance was high (89.5%). Overall, among
      postmenopausal women with a prior history of breast cancer, a 4-month course of 3
      mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3
      levels. Compliance was comparable between the two groups. Short-term melatonin
      treatment did not influence the estradiol and IGF-1/IGBBP-3 levels. Effects of
      longer courses of melatonin among premenopausal women are unknown. Low baseline
      estradiol levels in our study population may have hindered the ability to detect
      any further estradiol-lowering effects of melatonin.

PMID- 22370699
TI  - Reflux and Barrett's disease. Can we stop surveillance after 2011?

PMID- 22370700
TI  - European Society of Gastrointestinal Endoscopy (ESGE) Guideline Development
      Policy.
AB  - Numerous scientific publications explore the field of gastrointestinal (GI)
      endoscopy (a Pubmed search currently yields > 73000 results). Therefore,
      guidelines have become an indispensable tool for incorporating up-to-date
      knowledge into daily clinical care. Since the 1990 s, the issuing of guidelines
      has been a central task of the European Society of Gastrointestinal Endoscopy
      (ESGE). Here, the ESGE clarifies the types of policy documents that it issues and
      the methodology used to produce them, taking into account recent methodological
      developments.

PMID- 22370701
TI  - Temporary placement of fully covered self-expandable metal stents in biliary
      complications after liver transplantation.
AB  - In the present study we prospectively evaluated the safety and efficacy of
      temporary fully covered, self-expandable metal stents (fcSEMS) to treat biliary
      strictures (n = 9), leaks (n = 9), and combined lesions (n = 1) occurring after
      liver transplantation, when standard endoscopic attempts had failed. Placement of
      fcSEMS and their removal in scheduled patients were successful and without
      complications. Resolution of the biliary lesion was confirmed in 15 of 19
      patients (79 %). Treatment was not successful in two patients and not evaluable
      in 2 other patients. Complications occurred in 9 /19 patients (47 %): stent
      migration in 6, stent occlusion in 1, and de novo stricture after successful
      treatment of a biliary leak in 2. After a median follow-up of 12 months, one
      recurrent anastomotic stricture was noted. Temporary placement of fcSEMS in
      biliary strictures and leaks after liver transplantation provides satisfactory
      results even in patients who have undergone multiple previous conventional
      endoscopic attempts, and offers an alternative approach to surgical intervention.

PMID- 22370702
TI  - Endoscopic ultrasonography.

PMID- 22370703
TI  - Small-bowel endoscopy.

PMID- 22370704
TI  - Alternative complement pathway and factor B activities in rats with altered blood
      levels of thyroid hormone.
AB  - Evaluating the activity of the complement system under conditions of altered
      thyroid hormone levels might help elucidate the role of complement in triggering
      autoimmune processes. Here, we investigated alternative pathway (AP) activity in
      male Wistar rats (180 +/- 10 g) after altering their thyroid hormone levels by
      treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3
      and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic
      assays were performed to evaluate the lytic activity of the AP. Factor B activity
      was evaluated using factor B-deficient serum. An anti-human factor B antibody was
      used to measure factor B levels in serum by radial immunodiffusion. T3
      measurements in thyroidectomized animals or animals treated with PTU demonstrated
      a significant reduction in hormone levels compared to control. The results showed
      a reduction in AP lytic activity in rats treated with increasing amounts of T3
      (1, 10, or 50 ug). Factor B activity was also decreased in the sera of
      hyperthyroid rats treated with 1 to 50 ug T3. Additionally, treating rats with 25
      ug T3 significantly increased factor B levels in their sera (P < 0.01). In
      contrast, increased factor B concentration and activity (32%) were observed in
      hypothyroid rats. We conclude that alterations in thyroid hormone levels affect
      the activity of the AP and factor B, which may in turn affect the roles of AP and
      factor B in antibody production.

PMID- 22370705
TI  - Cardiovascular effects of the intracerebroventricular injection of
      adrenomedullin: roles of the peripheral vasopressin and central cholinergic
      systems.
AB  - Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300
      g) female rats (N = 7 in each group) the effects of intracerebroventricularly
      (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to
      determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral
      V1 receptors or the central cholinergic system play roles in these cardiovascular
      effects. Blood pressure and HR were observed before and for 30 min following drug
      injections. The following results were obtained: 1) icv ADM (750 ng/10 uL) caused
      an increase in both blood pressure and HR (DMAP = 11.8 +/- 2.3 mmHg and DeltaHR =
      39.7 +/- 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and
      ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood
      pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 ug/10 uL,
      icv) and the muscarinic receptor antagonist atropine (5 ug/10 uL, icv) prevented
      the stimulating effect of ADM on blood pressure. The effect of ADM on HR was
      blocked only by atropine (5 ug/10 uL, icv). 4) The V1 receptor antagonist [beta
      mercapto-beta-beta-cyclopentamethylenepropionyl1, O-me-Tyr2,Arg8]-vasopressin
      (V2255; 10 ug/kg), that was applied intravenously, prevented the effect of ADM on
      blood pressure and HR. This is the first study reporting the role of specific ADM
      and CGRP receptors, especially the role of nicotinic and muscarinic central
      cholinergic receptors and the role of peripheral V1 receptors in the increasing
      effects of icv ADM on blood pressure and HR.

PMID- 22370707
TI  - Linear and nonlinear analysis of heart rate variability in healthy subjects and
      after acute myocardial infarction in patients.
AB  - The objectives of this study were to evaluate and compare the use of linear and
      nonlinear methods for analysis of heart rate variability (HRV) in healthy
      subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR)
      was recorded for 15 min in the supine position in 10 patients with AMI taking
      beta-blockers (aged 57 +/- 9 years) and in 11 healthy subjects (aged 53 +/- 4
      years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency
      domain using low- and high-frequency bands in normalized units (nu; LFnu and
      HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There
      was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio
      index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and
      0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group
      (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of
      the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05):
      RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62;
      HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31,
      respectively. There was agreement between the methods, suggesting that these have
      the same power to evaluate autonomic modulation of HR in both AMI patients and
      healthy subjects. AMI contributed to a reduction in cardiac signal irregularity,
      higher sympathetic modulation and lower vagal modulation.

PMID- 22370706
TI  - Comparative proteomics analysis of chronic atrophic gastritis: changes of protein
      expression in chronic atrophic gastritis without Helicobacter pylori infection.
AB  - Chronic atrophic gastritis (CAG) is a very common gastritis and one of the major
      precursor lesions of gastric cancer, one of the most common cancers worldwide.
      The molecular mechanism underlying CAG is unclear, but its elucidation is
      essential for the prevention and early detection of gastric cancer and
      appropriate intervention. A combination of two-dimensional gel electrophoresis
      and mass spectrometry was used in the present study to analyze the differentially
      expressed proteins. Samples from 21 patients (9 females and 12 males; mean age:
      61.8 years) were used. We identified 18 differentially expressed proteins in CAG
      compared with matched normal mucosa. Eight proteins were up-regulated and 10 down
      regulated in CAG when compared with the same amounts of proteins in individually
      matched normal gastric mucosa. Two novel proteins, proteasome activator subunit 1
      (PSME1), which was down-regulated in CAG, and ribosomal protein S12 (RPS12),
      which was up-regulated in CAG, were further investigated. Their expression was
      validated by Western blot and RT-PCR in 15 CAG samples matched with normal
      mucosa. The expression level of RPS12 was significantly higher in CAG than in
      matched normal gastric mucosa (P < 0.05). In contrast, the expression level of
      PSME1 in CAG was significantly lower than in matched normal gastric mucosa (P <
      0.05). This study clearly demonstrated that there are some changes in protein
      expression between CAG and normal mucosa. In these changes, down-regulation of
      PSME1 and up-regulation of RPS12 could be involved in the development of CAG.
      Thus, the differentially expressed proteins might play important roles in CAG as
      functional molecules.

PMID- 22370709
TI  - Restoration of the rabbit corneal surface after total epithelial debridement and
      complete limbal excision.
AB  - How is the corneal epithelium restored when all of it plus the limbus have been
      eliminated? This investigation explored the possibility that this may be achieved
      through the conjunctival epithelium. The corneal epithelium of the right eye of
      12 rabbits (Oryctolagus cuniculus) was totally scraped followed by surgical
      excision of the limbus plus 1.0-1.5 mm of the adjacent conjunctiva. Antibiotics
      and corticosteroids were applied for 1 week after surgery. Histological and
      immunohistochemical techniques were used to monitor the events taking place on
      the eye surface 2 weeks and 1, 3 and 6 months thereafter. Initially, the corneal
      surface was covered by conjunctival-like epithelium. After 1 month and more
      prominently at 3 and 6 months an epithelium displaying the morphological features
      of the cornea and reacting with the AE5 antibody was covering the central region.
      It is likely that the corneal epithelium originated from undifferentiated cells
      of the conjunctiva interacting with the corneal stroma.

PMID- 22370708
TI  - Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis
      patients in the Dongting Lake region.
AB  - Major histocompatibility complex class I chain-related A (MICA) is a highly
      polymorphic gene located within the MHC class I region of the human genome.
      Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by
      binding to its cognate receptor on natural killer cells, NKG2D, and its genetic
      polymorphisms have been recently associated with susceptibility to some
      infectious diseases. We determined whether MICA polymorphisms were associated
      with the high rate of Schistosoma parasitic worm infection or severity of disease
      outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain
      reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT)
      were applied for high-resolution allele typing of schistosomiasis cases (N = 103,
      age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N =
      141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles
      and five short-tandem repeat (STR) alleles were identified among the two
      populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher
      frequency in healthy controls than in schistosomiasis patients, but the
      difference was not significantly correlated with susceptibility to S. japonicum
      infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was
      significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore,
      the distribution profile of MICA alleles in this Hunan Han population was
      significantly different from those published for Korean, Thai, American
      Caucasian, and Afro-American populations (P < 0.01), but similar to other Han
      populations within China (P > 0.05). This study provides the initial evidence
      that MICA genetic polymorphisms may underlie the severity of liver fibrosis
      occurring in schistosomiasis patients from the Dongting Lake region.

PMID- 22370710
TI  - Patterns of BCR breakpoints in patients with coexisting inv(16)(p13.1q22) and
      t(9;22)(q34;q11.2).

PMID- 22370711
TI  - Late effect of atomic bomb radiation on myeloid disorders: leukemia and
      myelodysplastic syndromes.
AB  - Leukemia was the first malignancy linked to radiation exposure in atomic bomb
      survivors. Clear evidence of the dose-dependent excess risk of three major types
      of leukemia (acute lymphocytic leukemia, acute myeloid leukemia [AML], and
      chronic myeloid leukemia) was found, especially in people exposed at young ages.
      Such leukemia risks were at their highest in the late 1950s, and declined
      gradually thereafter over the past 50 years. Findings from recent risk analyses,
      however, suggest the persistence of AML risk even after 1990, and evidence of
      increased risk of myelodysplastic syndromes (MDS) due to atomic bomb radiation
      has recently been shown. High-risk MDS and forms involving complex chromosomal
      aberrations were found to be much more frequent in people exposed to higher
      radiation doses. These lines of epidemiological evidence suggest that the risk of
      radiation-induced hematological malignancies has persisted for six decades since
      the initial exposure.

PMID- 22370712
TI  - Overview: effects of radiation on the human body: acute and chronic sequelae in
      hematopoietic organs.

PMID- 22370713
TI  - Metal speciation in a complexing soft film layer: a theoretical dielectric
      relaxation study of coupled chemodynamic and electrodynamic interfacial
      processes.
AB  - We report a comprehensive formalism for the dynamics of metal speciation across
      an interphase formed between a complexing soft film layer and an electrolyte
      solution containing indifferent ions and metal ions that form complexes with
      charged molecular ligands distributed throughout the film. The analysis
      integrates the intricate interplay between metal complexation kinetics and
      diffusive metal transfer from/toward the ligand film, together with the kinetics
      of metal electrostatic partitioning across the film/solution interphase. This
      partitioning is determined by the settling dynamics of the interfacial electric
      double layer (EDL), as governed by time-dependent conduction-diffusion transports
      of both indifferent and reactive metal ions. The coupling between such
      chemodynamic and electrodynamic processes is evaluated via derivation of the
      dielectric permittivity increment for the ligand film/electrolyte interphase that
      is perturbed upon application of an ac electric field (pulsation omega) between
      electrodes supporting the films. The dielectric response is obtained from the
      omega-dependent distributions of all ions across the ligand film, as ruled by
      coupled Poisson-Nernst-Planck equations amended for a chemical source term
      involving the intra-film complex formation and dissociation pulsations (omega(a)
      and omega(d) respectively). Dielectric spectra are discussed for bare and film
      coated-electrodes over a wide range of field pulsations and Deborah numbers De =
      omega(a,d)/omega(diff), where omega(diff) is the electric double layer relaxation
      pulsation. The frequency-dependent dynamic or inert character of the formed metal
      complexes is then addressed over a time window that ranges from transient to
      fully relaxed EDL. The shape and magnitude of the dielectric spectra are further
      shown to reflect the lability of dynamic complexes, i.e. whether the overall
      speciation process at a given pulsation omega is primarily rate-limited either by
      complexation kinetics or by ion-transport dynamics. The limits, strengths and
      extensions of the approach are further discussed within the context of metal
      speciation dynamics at soft planar and particulate complexing interphases.

PMID- 22370715
TI  - A PCR-based genotyping method to distinguish between wild-type and ornamental
      varieties of Imperata cylindrica.
AB  - Wild-type I. cylindrica (cogongrass) is one of the top ten worst invasive plants
      in the world, negatively impacting agricultural and natural resources in 73
      different countries throughout Africa, Asia, Europe, New Zealand, Oceania and the
      Americas(1-2). Cogongrass forms rapidly-spreading, monodominant stands that
      displace a large variety of native plant species and in turn threaten the native
      animals that depend on the displaced native plant species for forage and shelter.
      To add to the problem, an ornamental variety [I. cylindrica  var. koenigii
      (Retzius)] is widely marketed under the names of Imperata cylindrica 'Rubra', Red
      Baron, and Japanese blood grass (JBG). This variety is putatively sterile and
      noninvasive and is considered a desirable ornamental for its red-colored leaves.
      However, under the correct conditions, JBG can produce viable seed (Carol Holko,
      2009 personal communication) and can revert to a green invasive form that is
      often indistinguishable from cogongrass as it takes on the distinguishing
      characteristics of the wild-type invasive variety(4) (Figure 1). This makes
      identification using morphology a difficult task even for well-trained plant
      taxonomists. Reversion of JBG to an aggressive green phenotype is also not a rare
      occurrence. Using sequence comparisons of coding and variable regions in both
      nuclear and chloroplast DNA, we have confirmed that JBG has reverted to the green
      invasive within the states of Maryland, South Carolina, and Missouri. JBG has
      been sold and planted in just about every state in the continental U.S. where
      there is not an active cogongrass infestation. The extent of the revert problem
      in not well understood because reverted plants are undocumented and often
      destroyed.    Application of this molecular protocol provides a method to
      identify JBG reverts and can help keep these varieties from co-occurring and
      possibly hybridizing. Cogongrass is an obligate outcrosser and, when crossed with
      a different genotype, can produce viable wind-dispersed seeds that spread
      cogongrass over wide distances(5-7). JBG has a slightly different genotype than
      cogongrass and may be able to form viable hybrids with cogongrass. To add to the
      problem, JBG is more cold and shade tolerant than cogongrass(8-10), and gene flow
      between these two varieties is likely to generate hybrids that are more
      aggressive, shade tolerant, and cold hardy than wild-type cogongrass. While wild
      type cogongrass currently infests over 490 million hectares worldwide, in the
      Southeast U.S. it infests over 500,000 hectares and is capable of occupying most
      of the U.S. as it rapidly spreads northward due to its broad niche and geographic
      potential(3,7,11). The potential of a genetic crossing is a serious concern for
      the USDA-APHIS Federal Noxious Week Program. Currently, the USDA-APHIS prohibits
      JBG in states where there are major cogongrass infestations (e.g., Florida,
      Alabama, Mississippi). However, preventing the two varieties from combining can
      prove more difficult as cogongrass and JBG expand their distributions.
      Furthermore, the distribution of the JBG revert is currently unknown and without
      the ability to identify these varieties through morphology, some cogongrass
      infestations may be the result of JBG reverts. Unfortunately, current molecular
      methods of identification typically rely on AFLP (Amplified Fragment Length
      Polymorphisms) and DNA sequencing, both of which are time consuming and costly.
      Here, we present the first cost-effective and reliable PCR-based molecular
      genotyping method to accurately distinguish between cogongrass and JBG revert.

PMID- 22370716
TI  - Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor
      presence in breast cancer patients.
AB  - BACKGROUND: Trastuzumab is part of the standard treatment for patients with human
      epidermal growth factor receptor 2 (HER-2)-positive breast cancer, but not all
      patients respond to trastuzumab. Altered microRNA (miR) expression levels in
      cancer cells have been correlated with prognosis and response to chemotherapy.
      The authors of this report hypothesized that altered miR expression levels in
      plasma are associated with sensitivity to trastuzumab in patients with HER-2
      positive breast cancer. METHODS: Quantitative reverse transcriptase-polymerase
      chain reaction was used to analyze plasma samples, including samples from
      patients with breast cancer who were enrolled in a clinical trial of neoadjuvant
      trastuzumab-based chemotherapy. Expression levels of miR-210, miR-21, miR-29a,
      and miR-126 were analyzed according to the type of response (pathologic complete
      response [n = 18] vs residual disease [n = 11]). MicroRNA expression levels also
      were compared in trastuzumab-sensitive and trastuzumab-resistant breast cancer
      cells derived from BT474 cells and in an independent set of preoperative plasma
      samples (n = 39) and postoperative plasma samples (n = 30) from 43 breast cancer
      patients who did not receive any treatment. RESULTS: At baseline before patients
      received neoadjuvant chemotherapy combined with trastuzumab, circulating miR-210
      levels were significantly higher in those who had residual disease than in those
      who achieved a pathologic complete response (P = .0359). The mean expression
      ratio for miR-210 was significantly higher in trastuzumab-resistant BT474 cells,
      and miR-210 expression was significantly higher before surgery than after surgery
      (P = .0297) and in patients whose cancer metastasized to the lymph nodes (P =
      .0030). CONCLUSIONS: Circulating miR-210 levels were associated with trastuzumab
      sensitivity, tumor presence, and lymph node metastases. These results suggest
      that plasma miR-210 may be used to predict and perhaps monitor response to
      therapies that contain trastuzumab.

PMID- 22370717
TI  - HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a
      complex with CXCL12 and signaling via CXCR4.
AB  - After tissue damage, inflammatory cells infiltrate the tissue and release
      proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein
      released by necrotic and severely stressed cells, promotes cytokine release via
      its interaction with the TLR4 (Toll-like receptor 4) receptor and cell migration
      via an unknown mechanism. We show that HMGB1-induced recruitment of inflammatory
      cells depends on CXCL12. HMGB1 and CXCL12 form a heterocomplex, which we
      characterized by nuclear magnetic resonance and surface plasmon resonance, that
      acts exclusively through CXCR4 and not through other HMGB1 receptors.
      Fluorescence resonance energy transfer data show that the HMGB1-CXCL12
      heterocomplex promotes different conformational rearrangements of CXCR4 from that
      of CXCL12 alone. Mononuclear cell recruitment in vivo into air pouches and
      injured muscles depends on the heterocomplex and is inhibited by AMD3100 and
      glycyrrhizin. Thus, inflammatory cell recruitment and activation both depend on
      HMGB1 via different mechanisms.

PMID- 22370718
TI  - Dual regulation of IRF4 function in T and B cells is required for the
      coordination of T-B cell interactions and the prevention of autoimmunity.
AB  - Effective humoral responses to protein antigens require the precise execution of
      carefully timed differentiation programs in both T and B cell compartments.
      Disturbances in this process underlie the pathogenesis of many autoimmune
      disorders, including systemic lupus erythematosus (SLE). Interferon regulatory
      factor 4 (IRF4) is induced upon the activation of T and B cells and serves
      critical functions. In CD4(+) T helper cells, IRF4 plays an essential role in the
      regulation of IL-21 production, whereas in B cells it controls class switch
      recombination and plasma cell differentiation. IRF4 function in T helper cells
      can be modulated by its interaction with regulatory protein DEF6, a molecule that
      shares a high degree of homology with only one other protein, SWAP-70. Here, we
      demonstrate that on a C57BL/6 background the absence of both DEF6 and SWAP-70
      leads to the development of a lupus-like disease in female mice, marked by
      simultaneous deregulation of CD4(+) T cell IL-21 production and increased IL-21 B
      cell responsiveness. We furthermore show that DEF6 and SWAP-70 are differentially
      used at distinct stages of B cell differentiation to selectively control the
      ability of IRF4 to regulate IL-21 responsiveness in a stage-specific manner.
      Collectively, these data provide novel insights into the mechanisms that normally
      couple and coordinately regulate T and B cell responses to ensure tight control
      of productive T-B cell interactions.

PMID- 22370719
TI  - A germinal center-independent pathway generates unswitched memory B cells early
      in the primary response.
AB  - Memory B cells can be produced from the classical germinal center (GC) pathway or
      a less understood GC-independent route. We used antigen-based cell enrichment to
      assess the relative contributions of these pathways to the polyclonal memory B
      cell pool. We identified a CD38(+) GL7(+) B cell precursor population that
      differentiated directly into IgM(+) or isotype-switched (sw) Ig(+) memory B cells
      in a GC-independent fashion in response to strong CD40 stimulation.
      Alternatively, CD38(+) GL7(+) B cell precursors had the potential to become Bcl
      6(+) GC cells that then generated primarily swIg(+) memory B cells. These results
      demonstrate that early IgM(+) and swIg(+) memory B cells are products of a GC
      independent pathway, whereas later switched Ig(+) memory B cells are products of
      GC cells.

PMID- 22370721
TI  - Reduced dimensionality 3D HNCAN for unambiguous HN, CA and N assignment in
      proteins.
AB  - We present here an improvisation of HNN (Panchal, Bhavesh et al., 2001) called RD
      3D HNCAN for backbone (HN, CA and (15)N) assignment in both folded and unfolded
      proteins. This is a reduced dimensionality experiment which employs CA chemical
      shifts to improve dispersion. Distinct positive and negative peak patterns of
      various triplet segments along the polypeptide chain observed in HNN are retained
      and these provide start and check points for the sequential walk. Because of co
      incrementing of CA and (15)N, peaks along one of the dimensions appear at sums
      and differences of the CA and (15)N chemical shifts. This changes the backbone
      assignment protocol slightly and we present this in explicit detail. The
      performance of the experiment has been demonstrated using Ubiquitin and
      Plasmodium falciparum P2 proteins. The experiment is particularly valuable when
      two neighboring amino acid residues have nearly identical backbone (15)N chemical
      shifts.

PMID- 22370722
TI  - MAGIC SHIMMING: gradient shimming with magic angle sample spinning.
AB  - A simple method to automatically shim NMR samples spinning at the magic angle is
      introduced based on the gradient shimming approach. The field inhomogeneity along
      the spinning axis is measured and automatically corrected. The combination of a
      normal magic angle spinning (MAS) probe, a conventional homospoil gradient, and a
      set of properly chosen standard room-temperature shims are used to perform the
      gradient shimming of samples spinning at the magic angle. The resulting (13)C NMR
      adamantane linewidth is less than 1 Hz (0.0078 ppm at 11.7 T).

PMID- 22370720
TI  - An extra allele of Chk1 limits oncogene-induced replicative stress and promotes
      transformation.
AB  - Replicative stress (RS) is a type of endogenous DNA damage that cells suffer
      every time they duplicate their genomes, and which is further boosted by
      oncogenes. In mammals, the RS response (RSR) is coordinated by ATR and Chk1
      kinases. We sought to develop a mammalian organism that is selectively protected
      from RS. To this end, mice carrying an extra copy of the Chk1 gene were
      generated. In vitro, Chk1 transgenic cells are protected from RS-inducing agents.
      Moreover, an extra Chk1 allele prolongs the survival of ATR-Seckel mice, which
      suffer from high levels of RS, but not that of ATM-deficient mice, which
      accumulate DNA breaks. Surprisingly, increased Chk1 levels favor transformation,
      which we show is associated with a reduction in the levels of RS induced by
      oncogenes. Our study provides the first example where supra-physiological levels
      of a tumor suppressor can promote malignant transformation, which is a result of
      the protection from the RS found in cancer cells.

PMID- 22370723
TI  - Role of denosumab in prostate cancer.
AB  - Prostate cancer is known to have a tissue tropism for bone. This tissue tropism
      coupled with the experience with androgen deprivation therapy (ADT) over the past
      decade has led to heightened awareness of bone complications. Osteopenia and
      subsequent skeletal-related events (SREs) are one of the more concerning
      repercussions of ADT along with cardiovascular sequelae. To combat this decrease
      in bone mineral density, several agents have been developed for bone protection.
      The largest experience is with bisphosphonates (BPs), but recently (2011) head to
      head trials have established the role of monoclonal antibodies, particularly in
      patients with prostate cancer bone metastasis. For patients initiating ADT,
      monthly denosumab increased bone mineral density, the time for occurrence of any
      bone metastasis and time for symptomatic bone metastasis. Denosumab is a fully
      human monoclonal antibody of the IgG(2) subtype that selectively binds and
      neutralizes receptor activator NF kappa B ligand (RANKL), inhibiting
      osteoclastogenesis and bone turnover. In vitro binding assays have shown high
      affinity binding of denosumab and osteoprotegerin to both soluble and membrane
      bound forms of human RANKL. As clinicians may be less familiar with this newer
      agent, we compiled this review to summarize denosumab's current clinical
      indications for bone stabilization and mechanism of reduction in tumor burden.

PMID- 22370724
TI  - MTHFR polymorphism and the risk of prostate cancer: a meta-analysis of case
      control studies.
AB  - BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms
      implicated in the cancer development, but the published studies had yielded
      inconsistent results. METHODS: Pubmed was searched for all published case-control
      studies about MTHFR polymorphisms and prostate cancer risk. RESULTS: In all, 13
      studies including 5872 cases and 6255 controls described C677T genotypes, among
      which 9 articles, containing 2847 cases and 3657 controls described A1298C
      genotypes, were involved in our meta-analysis. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were estimated to assess the association between MTHFR
      polymorphisms and prostate cancer risk, heterogeneity, publication bias and
      sensitivity were also calculated. Overall, meta-analysis indicated that the 677T
      allele was more likely to exert protective effect on prostate cancer risk (random
      effects pooled OR, 0.78 (0.64-0.96); P=0.016 (P=0.033 for heterogeneity studies))
      in a recessive genetic model, no associations were found in other genetic models
      or in comparing a/a versus A/A homozygous. Neither did we find any difference in
      effects on high or low aggressive prostate cancer. No evidence of an association
      of MTHFR A1298C polymorphism with prostate cancer was found. CONCLUSIONS: C677T
      of the MTHFR gene may provide protective effects on susceptibility to prostate
      cancer risk.

PMID- 22370725
TI  - Growth/differentiation factor-15: prostate cancer suppressor or promoter?
AB  - Deregulation of expression and function of cytokines belonging to the
      transforming growth factor-beta (TGF-beta) family is often associated with
      various pathologies. For example, this cytokine family has been considered a
      promising target for cancer therapy. However, the detailed functions of several
      cytokines from the TGF-beta family that could have a role in cancer progression
      and therapy remain unclear. One of these molecules is growth/differentiation
      factor-15 (GDF-15), a divergent member of the TGF-beta family. This stress
      induced cytokine has been proposed to possess immunomodulatory functions and its
      high expression is often associated with cancer progression, including prostate
      cancer (PCa). However, studies clearly demonstrating the mechanisms for signal
      transduction and functions in cell interaction, cancer progression and therapy
      are still lacking. New GDF-15 roles have recently been identified for modulating
      osteoclast differentiation and for therapy for PCa bone metastases. Moreover, GDF
      15 is as an abundant cytokine in seminal plasma with immunosuppressive
      properties. We discuss studies that focus on the regulation of GDF-15 expression
      and its role in tissue homeostasis, repair and the immune response with an
      emphasis on the role in PCa development.

PMID- 22370726
TI  - DeSUMOylating isopeptidase: a second class of SUMO protease.
AB  - The modification of proteins by small ubiquitin-like modifier (SUMO) is crucial
      for the regulation of diverse cellular processes. Protein SUMOylation is reversed
      by isopeptidases, collectively known as deSUMOylases. Only one family of SUMO
      specific proteases has been described so far: the sentrin-specific proteases
      (SENP). Here, we identify and characterize a new deSUMOylase, which we have named
      DeSI-1 (DeSumoylating Isopeptidase 1). We describe BZEL-a new transcriptional
      repressor-as substrate of DeSI-1. DeSI-1 catalyses the deSUMOylation, but not the
      deubiquitination, of BZEL. Furthermore, the SENP substrates PML and DeltaNp63 are
      not deSUMOylated by DeSI-1, suggesting that SENP and DeSI enzymes recognize
      different sets of substrates. Together, these data identify a second class of
      SUMO proteases.

PMID- 22370727
TI  - Cargo ubiquitination is essential for multivesicular  body intralumenal vesicle
      formation.
AB  - The efficient formation of a variety of transport vesicles is influenced by the
      presence of cargo, suggesting that cargo itself might have a defining role in
      vesicle biogenesis. However, definitive in vivo experiments supporting this
      concept are lacking, as it is difficult to eliminate endogenous cargo. The
      Endosomal Sorting Complexes Required for Transport (ESCRT) apparatus sorts
      ubiquitinated membrane proteins into endosomal intralumenal vesicles (ILVs) that
      accumulate within multivesicular bodies. Here we show that cargo ubiquitination
      is required for effective recruitment of the ESCRT machinery onto endosomal
      membranes and for the subsequent formation of ILVs.

PMID- 22370728
TI  - Molecules of choice?

PMID- 22370729
TI  - Preventive and curative care utilization among Mexican immigrant women in
      Birmingham, AL.
AB  - This study aims to describe the utilization of curative and preventive care among
      Mexican immigrant women in the country of origin versus the US, and to identify
      factors associated with preventive and curative care utilization. A cross
      sectional sample of 185 Mexican immigrant women living in Birmingham, AL between
      2004 and 2005 were included in this study. Fisher's Exact tests showed that there
      was a statistically significant difference between seeking curative care (p <
      0.0001) and preventive care (p < 0.0001) in country of origin versus the US.
      Differences in the reasons for lack of utilization of both curative and
      preventive care were also observed in the US and the country of origin. These
      findings suggest that difference in healthcare-seeking behaviors and utilization
      among Mexican immigrant women between the US and their country of origin may be
      useful in the development of interventions aimed at increasing the use of
      preventive and curative care services to this immigrant population in the US.

PMID- 22370730
TI  - High-risk sexual behavior, HIV/STD prevalence, and risk predictors in the social
      networks of young Roma (Gypsy) men in Bulgaria.
AB  - Roma (Gypsies), the largest and most disadvantaged ethnic minority group in
      Europe, are believed to be vulnerable to HIV/AIDS. This study's aim was to
      examine HIV risk in 6 Roma male sociocentric networks (n = 405 men) in Bulgaria.
      Participants were interviewed concerning their risk practices and tested for
      HIV/STDs. High-risk sexual behaviors were common. Over 57% of men had multiple
      sexual partners in the past 3 months. Over one-third of men reported both male
      and female partners in the past year. Condom use was low. Greater levels of
      sexual risk were associated with lower intentions and self-efficacy for using
      condoms, drug use, having male partners, knowing HIV-positive persons, and having
      higher AIDS knowledge but no prior HIV testing. Two men had HIV infection, 3.7%
      gonorrhea, and 5.2% chlamydia. HIV prevention interventions directed toward high
      risk social networks of Roma are needed before HIV infection becomes more widely
      established.

PMID- 22370731
TI  - Radiologic assessment of a self-shield with boron-containing water for a compact
      medical cyclotron.
AB  - The cyclotron at our hospital has a self-shield of boron-containing water. The
      amount of induced radioactivity in the boron-containing water shield of a compact
      medical cyclotron has not yet been reported. In this study, we measured the
      photon and neutron dose rates outside the self-shield during cyclotron operation.
      We estimated the induced radioactivities of the boron-containing water used for
      the self-shield and then measured them. We estimated the activation of concrete
      outside the self-shield in the cyclotron laboratory. The thermal neutron flux
      during cyclotron operation was estimated to be 4.72 * 10(2) cm(-2) s(-1), and the
      activation of concrete in a cyclotron laboratory was about three orders of
      magnitude lower than the clearance level of RS-G-1.7 (IAEA). The activity
      concentration of the boron-containing water did not exceed the concentration
      limit for radioactive isotopes in drainage in Japan and the exemption level for
      Basic Safety Standards. Consequently, the boron-containing water is treatable as
      non-radioactive waste. Neutrons were effectively shielded by the self-shield
      during cyclotron operation.

PMID- 22370732
TI  - Resection margin with anatomic or nonanatomic hepatectomy for liver metastasis
      from colorectal cancer.
AB  - BACKGROUND: When hepatectomy is used as a primary treatment for liver metastasis
      from colorectal cancer (CRCLM), the balance between surgical curability and
      functional preservation of the remnant liver is of great importance. METHODS: A
      total of 108 patients who underwent initial hepatectomy for CRCLM were
      retrospectively analyzed with respect to tumor extent, operative method, and
      prognosis, including recurrence. RESULTS: The 1-, 2-, 3-, and 5-year overall
      survival rates (OS) for all patients were 90.5%, 77.8%, 63.2%, and 51.6%,
      respectively. Multivariate analysis indicated serum carbohydrate antigen 19-9 (CA
      19-9) level after hepatectomy (<36 or >=36 mAU/mL) and presence of recurrence as
      independent prognostic factors of OS (P = 0.0458 and 0.0249, respectively), and
      tumor depth of colorectal cancer (<se (a2) vs. >=se (a2)) and serum CA 19-9 level
      after hepatectomy as the significant factors affecting disease-free survival
      (DFS) (P = 0.0025 and 0.00138, respectively). Neither resection margin nor type
      of hepatectomy (anatomic or nonanatomic) for CRCLM was a significant prognostic
      factor for OS or DFS or CRCLM recurrence, including intrahepatic recurrence.
      CONCLUSIONS: In CRCLM, we believe that nonanatomic hepatectomy with narrow margin
      is indicated, and optimal treatment would include functional preservation of as
      much of the remnant liver as possible.

PMID- 22370733
TI  - Pancreatic lesions in von Hippel-Lindau disease? A systematic review and meta
      synthesis of the literature.
AB  - BACKGROUND: von Hippel-Lindau (vHL) disease is a rare condition that leads to
      characteristic lesions within many different body systems. Pancreatic
      manifestations of vHL cover a wide spectrum of pathologies, and thus, accurate
      characterization and management is critical. METHODS: A comprehensive and
      systematic text word and MeSH search of the medical literature was performed to
      identify studies where information regarding the prevalence, clinical
      characteristics, and management recommendations could be extracted. RESULTS:
      Eleven studies were identified but 2 studies utilized the same data set. Of the
      10 remaining studies, a total of 1,442 patients with vHL were available for
      analysis. Four hundred and twenty patients were examined for any type of
      pancreatic lesion, 362 for simple cysts or serous cystadenomas (SCAs), and 1,442
      for neuroendocrine tumors (NETs). Of the 420 assessed for any pancreatic
      manifestation of vHL, 252 (60%) had a pancreatic lesion identified. Simple cysts
      that present as the sole manifestation of pancreatic disease were common and
      found in 169 of 362 (47%) patients. These are usually asymptomatic and do not
      normally require intervention. SCAs were reported in 39 of 362 (11%) patients and
      followed a similar benign course; resection is acceptable in symptomatic
      patients. NETs were identified in 211 of 1,442 (15%) patients, and 27 of 1,442
      (2%) lesions behaved malignantly. Management of NETs depends on size, doubling
      time, and underlying genetics. Renal cell carcinoma is a characteristic in vHL,
      but there were no cases of pancreatic metastases identified from the included
      studies. Adenocarcinomas of the pancreas are not pathogenically linked to vHL.
      CONCLUSIONS: This review highlights the wide spectrum and high prevalence of
      pancreatic lesions in vHL. Simple cysts and SCAs are benign, but NETs require
      careful observation due to their malignant potential.

PMID- 22370734
TI  - Appendiceal intussusception masquerading as an ileocolic intussusception.
AB  - INTRODUCTION: Appendiceal intussusception is rare occurring with an incidence of
      0.1%. It is most commonly encountered in middle-aged females due to endometrial
      involvement of the appendix. CLINICAL DATA: One-quarter of cases occur in the
      pediatric population where it is usually due to appendiceal inflammation.
      DISCUSSION: Classification of appendiceal intussusception (type I-V) is based on
      the level of appendiceal invagination. Appendectomy is the treatment of choice
      unless there is a concern for a neoplasm in which case a more extensive resection
      may be necessary. We report a 47-year-old with an appendiceal intussusception.

PMID- 22370735
TI  - Outcome of right hepatectomy for living liver donors: a single Egyptian center
      experience.
AB  - BACKGROUND: This study aims to evaluate living liver donor outcome after right
      hepatectomy in a single Egyptian center. PATIENTS AND METHODS: Between April 2004
      and July 2010, 100 living donors underwent right hepatectomy. Their medical
      records and postoperative follow-up visits were retrospectively revised.
      Perioperative complications were reported. Postoperative complications were
      classified according to the five tier version of Clavien system. RESULTS: There
      were 71 males and 29 females. The mean age was 27.6 +/- 7.4 years. The mean graft
      weight was 999 +/- 167 g and the mean volume percent of the remaining liver was
      36.8 +/- 8%. The mean ICU and hospital stay were 2.6 +/- 2.7 and 12.4 +/- 9.1,
      respectively. A total of 57 complications developed in 38 donors (38%). The
      commonest complication type was biliary complications. There were 22 grade I, 6
      grade II, 15 grade IIIa, 12 grade IIIb, 1 grade IVa, and 1 grade V complications.
      One donor died due to posttransfusion ARDS on the 30th postoperative day. On
      follow-up, no donor developed long lasting disability. A donor died in a road
      traffic accident 1 year after donation. DISCUSSION AND CONCLUSIONS: Donor right
      hepatectomy is not an entirely safe procedure. Biliary complications are the
      commonest early postoperative complications.

PMID- 22370736
TI  - First-principles calculations on the four phases of BaTiO3.
AB  - The calculations based on linear combination of atomic orbitals basis functions
      as implemented in CRYSTAL09 computer code have been performed for cubic,
      tetragonal, orthorhombic, and rhombohedral modifications of BaTiO(3) crystal.
      Structural and electronic properties as well as phonon frequencies were obtained
      using local density approximation, generalized gradient approximation, and hybrid
      exchange-correlation density functional theory (DFT) functionals for four stable
      phases of BaTiO(3). A comparison was made between the results of different DFT
      techniques. It is concluded that the hybrid PBE0 [J. P. Perdew, K. Burke, M.
      Ernzerhof, J. Chem. Phys. 1996, 105, 9982.] functional is able to predict
      correctly the structural stability and phonon properties both for cubic and
      ferroelectric phases of BaTiO(3). The comparative phonon symmetry analysis in
      BaTiO(3) four phases has been made basing on the site symmetry and irreducible
      representation indexes for the first time.

PMID- 22370737
TI  - Thrombosis on implanted device for atrial septal defect closure or
      echocardiographic beam width artifact? A diagnostic enigma!
AB  - A 29 year old woman with NYHA functional class II and large secundum type atrial
      septal defect (ASD) underwent successfully percutaneous ASD closure with Figula
      ASD occluder (no. 30) without any peri-procedural complication. After 2 days she
      underwent transthoracic echocardiography and a large hypo-echoic mass was seen on
      left atrial side of implanted device in multiple views, suggestive of thrombosis
      or echocardiographic beam width artifact? A diagnostic enigma!

PMID- 22370738
TI  - The impact of future summer temperature on public health in Barcelona and
      Catalonia, Spain.
AB  - Several epidemiological studies have reported associations between increases in
      summer temperatures and risks of premature mortality. The quantitative
      implications of predicted future increases in summer temperature, however, have
      not been extensively characterized. We have quantified these effects for the four
      main cities in Catalonia, Spain (Barcelona, Tarragona, Lleida, Girona). We first
      used case-crossover analysis to estimate the association between temperature and
      mortality for each of these cities for the period 1983 to 2006. These exposure
      response (ER) functions were then combined with local measures of current and
      projected changes in population, mortality and temperature for the years 2025 and
      2050. Predicted daily mean temperatures were based on the A1B greenhouse gas
      emission, "business-as-usual" scenario simulations derived from the ENSEMBLES
      project. Several different ER functions were examined and significant
      associations between temperature and mortality were observed for all four cities.
      For these four cities, the age-specific piecewise linear model predicts 520
      (95%CI  340, 720) additional annual deaths attributable to the change in
      temperature in 2025 relative to the average from the baseline period of 1960
      1990. For 2050, the estimate increases to 1,610 deaths per year during the warm
      season. For Catalonia as a whole, the point estimates for those two years are 720
      and 2,330 deaths per year, respectively, or about 2 and 3% of the warm season. In
      comparing these predicted impacts with current causes of mortality, they clearly
      represent significant burdens to public health in Catalonia.

PMID- 22370739
TI  - The new oral adenosine A1 receptor agonist capadenoson in male patients with
      stable angina.
AB  - BACKGROUND: Anti-ischaemic effect of A1 adenosine receptor agonists was shown in
      animal and preclinical studies. The present proof-of-concept study aimed at
      evaluation of the efficacy and safety of a new adenosine A1 receptor agonist
      capadenoson in patients with stable angina. METHODS: This was a randomized,
      double-blind, placebo-controlled, single dose-escalating, multicenter trial
      comparing the effect of capadenoson at 1, 2.5, 5, 10, and 20 mg versus placebo.
      For each dose step patients were randomized to receive single doses of either
      capadenoson or matching placebo in a 5:1 ratio. The primary efficacy variable was
      the absolute difference in heart rate (HR) at maximum comparable level of
      workload between baseline and post dose exercise tolerance test at maximum
      concentration of capadenoson. Capadenoson effect on total exercise time and time
      to 1-mm ST-segment depression were also measured. RESULTS: Sixty-two male
      patients with stable angina were enrolled in the study. There was a consistent
      trend for HR reduction at comparable maximum work load in active treatment
      groups, with significant differences against placebo for 10 and 20 mg (HR
      reduction by 12.2 and 6.8 beats per min, p = 0.0002 and p = 0.032, respectively).
      A statistically significant trend (p = 0.0003) for a reduction in HR with
      increasing doses of capadenoson was shown. Increases in total exercise time and
      time to 1-mm ST-segment depression were also observed. CONCLUSIONS: In patients
      with stable angina capadenoson lowers exercise HR at comparable maximum workload,
      which is associated with improved total exercise time and prolongation of time to
      ischaemia.

PMID- 22370740
TI  - Is MtnE, the fifth Drosophila metallothionein, functionally distinct from the
      other members of this polymorphic protein family?
AB  - Metallothioneins (MTs) are a super-family of small, Cys-rich, non-homologous
      proteins that bind metal ions through the formation of metal-thiolate bonds.
      Although universally ubiquitous, they exhibit distinct metal-binding preferences,
      either for divalent (Zn-thioneins) or monovalent (Cu-thioneins) metal ions.
      Drosophila constitutes a bizarre exception, since it is currently the only case
      of metazoans synthesizing only Cu-thioneins, which are similar to the
      paradigmatic yeast Cup1 protein. Until recently, the Drosophila MT system was
      assumed to be composed of 4 isoforms (MtnA, MtnB, MtnC and MtnD), all of them
      responsive to heavy metal load through the dMTF1 transcription factor. The
      significance of this polymorphism has been analyzed in depth both at genomic and
      proteomic levels. Singularly, a fifth MT isoform was recently annotated and named
      MtnE. The analysis of the MtnE expression pattern revealed some differential
      traits with regard to the other MTs. We analyze here the peculiarities of the
      metal binding abilities of the MtnE polypeptide and compare them with those of
      the other Drosophila MTs determined through the same rationale. Characterization
      by ESI-MS spectrometry and CD and UV-visible spectrophotometry of the Zn(II)-,
      Cd(II)- and Cu(I)-MtnE complexes obtained by recombinant synthesis demonstrates
      that MtnE is the least metal-specific isoform of the Drosophila MTs, and
      therefore it could play a role when/where a broad spectrum of metal coordination
      abilities are advantageous in terms of physiological needs.

PMID- 22370741
TI  - Variant and invariant features characterizing natural and reverse whole-body
      pointing movements.
AB  - Previous investigations showed that kinematics and muscle activity associated
      with natural whole-body movements along the gravity direction present modular
      organizations encoding specific aspects relative to both the motor plans and the
      motor programmes underlying movement execution. It is, however, still unknown
      whether such modular structures characterize also the reverse movements, when the
      displacement of a large number of joints is required to take the whole body back
      to a standing initial posture. To study what motor patterns are conserved across
      the reversal of movement direction, principal component analysis and non-negative
      matrix factorization were therefore applied, respectively, to the time series
      describing the temporal evolution of the elevation angles associated with all the
      body links and to the electromyographic signals of both natural and reverse whole
      body movements. Results revealed that elevation angles were highly co-varying in
      time and that despite some differences in the global parameters characterizing
      the different movements (indicating differences in high-level variable associated
      with the selected motor plans), the level of joint co-variation did not change
      across movement direction. In contrast, muscle organization of the forward whole
      body pointing tasks was found to be different with respect to that characterizing
      the reverse movements. Such results agree with previous findings, according to
      which the central nervous system exploits, dependently on the direction of
      motion, different motor plans for the execution of whole-body movements. However,
      in addition, this study shows how such motor plans are translated into different
      muscle strategies that equivalently assure a high level of co-variation in the
      joint space.

PMID- 22370743
TI  - LOX genes in blast fungus (Magnaporthe grisea) resistance in rice.
AB  - Plant Lipoxygenases (LOX) are known to play major role in plant immunity by
      providing front-line defense against pathogen-induced injury. To verify this, we
      isolated a full-length OsLOX3 gene and also 12 OsLOX cDNA clones from Oryza
      sativa indica (cultivar Pusa Basmati 1). We have examined the role played by LOXs
      in plant development and during attack by blast pathogen Magnaporthe grisea. Gene
      expression, promoter region analysis, and biochemical and protein structure
      analysis of isolated OsLOX3 revealed significant homology with LOX super family.
      Protein sequence comparison of OsLOXs revealed high levels of homology when
      compared with japonica rice (up to100%) and Arabidopsis (up to 64%). Isolated
      LOX3 gene and 12 OsLOX cDNAs contained the catalytic LOX domains much required
      for oxygen binding and synthesis of oxylipins. Amino acid composition, protein
      secondary structure, and promoter region analysis (with abundance of motifs CGTCA
      and TGACG) support the role of OsLOX3 gene in providing resistance to diseases in
      rice plants. OsLOX3 gene expression analysis of root, shoot, flag leaf, and
      developing and mature seed revealed organ specific patterns during rice plant
      development and gave evidence to association between tissue location and
      physiological roles played by individual OsLOXs. Increased defense activity of
      oxylipins was observed as demonstrated by PCR amplification of OsLOX3 gene and
      upon inoculation with virulent strains of M. grisea and ectopic application of
      methyl jasmonate in the injured leaf tissue in adult rice plants.

PMID- 22370746
TI  - Isolation and antifungal susceptibility testing of Trichosporon asahii in Ceara,
      Brazil.
AB  - Trichosporon spp. are yeasts capable of causing invasive disease, which mainly
      affect immunocompromised patients. A clinical strain of T. asahii was isolated
      from the blood cultures of patients admitted to the General Hospital of
      Fortaleza. Susceptibility tests were conducted by disk diffusion and broth
      microdilution. The isolated strain of T. asahii was resistant to fluconazole. The
      patient used amphotericin B and caspofungin in order to facilitate the
      microbiological cure. It was the first isolation and identification of T. asahii
      in blood culture in Ceara, Brazil.

PMID- 22370744
TI  - Genome change in wheat observed through the structure and expression of
      alpha/beta-gliadin genes.
AB  - To better understand genome structure and the expression of alpha/beta-gliadin
      multigenes in hexaploid wheat, bacterial artificial chromosome (BAC) clones
      containing alpha/beta-gliadin genes from the three loci, Gli-A2, Gli-B2, and Gli
      D2, were screened. Based on their restriction fragment patterns, we selected five
      BAC clones, namely, two clones for Gli-A2, two clones for Gli-B2, and one clone
      for Gli-D2, to fully sequence. Approximately 200 kb was sequenced for each locus.
      In total, twelve alpha/beta-gliadin intact genes and four pseudogenes were found,
      and retrotransposons or other transposons existed in each BAC clone. Dot-plot
      analysis revealed the pattern of genome segmental duplication within each BAC. We
      calculated time since duplication of each set of alpha/beta-gliadin genes and
      insertion of retrotransposons. Duplication of all adjacent genes within the same
      BAC clone took place before or after allotetrapolyploidization, but duplication
      of certain genes occurred before diploid differentiation of wheat species.
      Retrotransposons were also inserted before and after the segmental duplication
      events. Furthermore, translocation of alpha/beta-gliadin genes from chromosomes 1
      to 6 apparently occurred before the diversification of various wheat genomes.
      Duplication of genome segments containing alpha/beta-gliadin genes and
      retrotransposons were brought about through unequal crossing-over or saltatory
      replication and alpha/beta-gliadin genes per se were duplicated without any
      recombination events. Out of twelve intact alpha/beta-gliadin genes detected from
      their sequences, nine were expressed, although their patterns of expression were
      distinct. Since they have similar cis-elements and promoter structures, the
      mechanisms underlying their distinct gene expression and possible applications
      are discussed.

PMID- 22370747
TI  - Fungal agents in different anatomical sites in Public Health Services in Cuiaba,
      state of Mato Grosso, Brazil.
AB  - INTRODUCTION: A contribution to the regional epidemiological profile of the most
      common fungal agents in Public Health Services in Cuiaba, state of Mato Grosso,
      including university hospitals and polyclinics. METHODS: Clinical specimens (n =
      1,496) from 1,078 patients were collected, submitted to direct mycological exam
      (potash or stick tape method) and cultured in specific mediums. Dermatophytic and
      non-dermatophytic agents were identified according to micromorphology (Ridell
      technique). RESULTS: The majority of the 1,496 specimens were skin (n = 985) and
      nail exams (n = 472). Of the 800 positive cultures, 246 (30.8%) corresponded to
      dermatophytes and 336 (42%) to yeasts of the genus Candida, 190 (23.7%) to other
      yeasts, 27 (3.4%) to non-dermatophytic filamentous fungi and one (0.1%) the agent
      of subcutaneous mycosis. Lesions considered primary occurred in greater numbers
      (59.5%) than recurrent lesions (37.4%), with a greater concentration of
      positivity occurring on the arms and legs. CONCLUSIONS: Comorbidities, allergies
      and diabetes mellitus were conditions associated with greater positivity in
      direct mycological exams and cultures. Positive culture was considered a
      definitive diagnosis of fungal infection and confirmed 47.8% of diagnostic
      hypotheses.

PMID- 22370742
TI  - Optimal feedback control and the long-latency stretch response.
AB  - There has traditionally been a separation between voluntary control processes and
      the fast feedback responses which follow mechanical perturbations (i.e., stretch
      "reflexes"). However, a recent theory of motor control, based on optimal control,
      suggests that voluntary motor behavior involves the sophisticated manipulation of
      sensory feedback. We have recently proposed that one implication of this theory
      is that the long-latency stretch "reflex", like voluntary control, should support
      a rich assortment of behaviors because these two processes are intimately linked
      through shared neural circuitry including primary motor cortex. In this review,
      we first describe the basic principles of optimal feedback control related to
      voluntary motor behavior. We then explore the functional properties of upper-limb
      stretch responses, with a focus on how the sophistication of the long-latency
      stretch response rivals voluntary control. And last, we describe the neural
      circuitry that underlies the long-latency stretch response and detail the
      evidence that primary motor cortex participates in sophisticated feedback
      responses to mechanical perturbations.

PMID- 22370748
TI  - Circulation of human papillomavirus (HPV) genotypes in women from Cordoba,
      Argentina, with squamous intraepithelial lesions.
AB  - Human papillomavirus (HPV) can induce a wide spectrum of squamous intraepithelial
      lesions (SIL) of varying severity. The aim of the present study was to establish
      the frequency of HPV infection and identify the genotypes circulating in women
      from Cordoba, Argentina, in relation to age and cytology. A total of 186 women,
      between 18 and 65 years old, with antecedents of SIL, underwent a pelvic
      examination and had cervical cells collected for cytology and HPV DNA detection.
      Ninety-six samples (51.6%) were positive for HPV detection, and sixty-three
      (65.6%) of them showed the presence of at least one HR-HPV. Low- and high-grade
      SIL showed significant association in patients younger than 35 years of age. We
      found 18 different genotypes, with a greater presence of HR-HPV. Genotypes 16 and
      6 were the most frequent. Seven (7.3%) multiple infections, 85.7% of which had at
      least one HR-HPV, were detected. The detection of a large number of different HPV
      genotypes is a warning sign. It is thus necessary to strengthen the monitoring of
      the circulation of high-risk genotypes, currently less prevalent in
      intraepithelial lesions, as a control measure for the possible impact of the
      implementation of vaccines against genotypes 16 and 18.

PMID- 22370749
TI  - Oral colonization by yeasts in HIV-positive patients in Brazil.
AB  - INTRODUCTION: In HIV-infected patients, colonization of the oral cavity by
      potential pathogenic yeast may lead to development of systemic fungemia. We
      evaluated the prevalence of yeast in the oral cavity of Brazilian HIV-positive
      patients and verified whether or not the species characterized were enzymatically
      active. Furthermore, the species identified were tested for their susceptibility
      to antifungal treatment. METHODS: Patient saliva and oropharyngeal candidiasis
      samples were collected from 60 seropositive HIV patients and identified by the
      API20C system. Enzymatic activity was evaluated by the production of proteinase
      and phospholipase. Susceptibility to antifungal treatments were determined using
      the broth microdilution method. RESULTS: the most commonly isolated species were
      C. albicans (51.56%) followed by non-albicans Candida species (43.73%),
      Trichosporon mucoides (3.12%) and Kodamaea ohmeri (1.56%). Oral colonization by
      association of different species was observed in 42% of the patients. Enzymatic
      activity was verified in most of species isolated, except for C. glabrata, C.
      lusitaniae and C. guilliermondii. Resistance to Fluconazole and Amphotericin B
      was observed in isolates of C. albicans, C. glabrata, C. parapsilosis, C. krusei,
      and K. ohmeri. CONCLUSION: HIV-positive patients are orally colonized by single
      or multiple species of yeast that are occasionally resistant to Fluconazole or
      Amphotericin B.

PMID- 22370750
TI  - HIV-1-mother-to-child transmission and associated characteristics in a public
      maternity unit in Presidente Prudente, Brazil.
AB  - In children, vertical transmission is the main form of HIV infection. Our aim was
      to determine the prevalence of HIV-1 vertical transmission in mother-infant pairs
      in a public maternity ward in Presidente Prudente, SP. Additionally; we sought to
      identify characteristics associated with this form of transmission. The files of
      86 HIV-1-infected mothers and their newborns referred to a Public Hospital from
      March 2002 to March 2007 were analyzed. The HIV-1-RNA viral load of the newborns
      was determined by bDNA. The HIV-1 vertical-transmission rate was 4.6%. Children
      that were born in the pre-term period and breastfed were at a higher risk of HIV
      1 infection (p = 0.005 and p = 0.017 respectively) than children born at term and
      not breastfed. Prophylactic therapy with zidovudine after birth for newborns was
      associated with a lower risk of infection (p = 0.003). The number of newborns
      weighing < 2,500 g was significantly higher for infected children (p = 0.008)
      than for non-infected newborns. About 22.9% of mothers did not know the HIV-1
      status of their newborns eight months after delivery. The study suggests that it
      is necessary to increase the identification of HIV-1 infection in pregnant women
      and their newborns as well as to offer and explain the benefits of ARV
      prophylaxis.

PMID- 22370751
TI  - Evaluation of GBV-C / HVG viremia in HIV-infected women.
AB  - The present study aimed at standardizing a real-time quantitative polymerase
      chain reaction assay to evaluate the presence of GBV-C/HGV RNA. A "TaqMan" assay
      using primers and probe derived from the 5c NCR region was developed and
      validated. Two hundred and fifty-three plasma samples from HIV-infected women
      were tested for GBV-C viremia and antibody against the envelope protein 2. GBV-C
      RNA was detected in 22.5% of the patients whereas the antibody was identified in
      25.3% of the cohort. Detection of viral RNA and of antibodies was mutually
      exclusive. Viral loads showed a mean of 1,777 arbitrary units / mL, being 1.1 and
      13,625 arbitrary units / mL respectively the lowest and highest values measured.
      We conclude that the real-time quantitative polymerase chain reaction method
      developed is appropriate for the investigation of GBV-C RNA since it was shown to
      be highly specific and sensitive, as well as requiring few steps, preventing
      contamination and providing additional information as to the relative viremia of
      carriers, a parameter that must be included in studies evaluating the co-factors
      influencing the clinical outcome of HIV/AIDS.

PMID- 22370752
TI  - Safety and skin delayed-type hypersensitivity response in vervet monkeys
      immunized with Leishmania donovani sonicate antigen delivered with adjuvants.
AB  - In this study, we report on the safety and skin delayed-type hypersensitivity
      (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered
      in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl
      lipid A (MPLA) in groups of vervet monkeys. Following three intradermal
      injections of the inoculums on days 0, 28 and 42, safety and DTH responses were
      assessed. Preliminary tumor necrosis factor alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) levels were also measured and these were compared with DTH.
      Only those animals immunized with alum-BCG reacted adversely to the inoculum by
      producing ulcerative erythematous skin indurations. Non-parametric analysis of
      variance followed by a post-test showed significantly higher DTH responses in the
      MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group
      indicated significantly lower DTH responses to the sonicate antigen compared with
      the AlBCG+Ag group. There was a significant correlation between the DTH and
      cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania
      donovani sonicate antigen containing MISA 720 is safe and is associated with a
      strong DTH reaction following immunization.

PMID- 22370753
TI  - Diagnosing visceral leishmaniasis and HIV/AIDS co-infection: a case series study
      in Pernambuco, Brazil.
AB  - HIV/AIDS-associated visceral leishmaniasis may display the characteristics of an
      aggressive disease or without specific symptoms at all, thus making diagnosis
      difficult. The present study describes the results of diagnostic tests applied to
      a series of suspected VL cases in HIV-infected/AIDS patients admitted in referral
      hospitals in Pernambuco, Brazil. From a total of 14 eligible patients with
      cytopenias and/or fever of an unknown etiology, and indication of bone marrow
      aspirate, 10 patients were selected for inclusion in the study. Diagnosis was
      confirmed by the following examinations: Leishmania detection in bone marrow
      aspirate, direct agglutination test, indirect immunofluorescence, rK39 dipstick
      test, polymerase chain reaction and latex agglutination test. Five out of the ten
      patients were diagnosed with co-infection. A positive direct agglutination test
      was recorded for all five co-infected patients, the Leishmania detection and
      latex agglutination tests were positive in four patients, the rK39 dipstick test
      in three, the indirect immunofluorescence in two and a positive polymerase chain
      reaction was recorded for one patient. This series of cases was the first to be
      conducted in Brazil using this set of tests in order to detect co-infection.
      However, no consensus has thus far been reached regarding the most appropriate
      examination for the screening and monitoring of this group of patients.

PMID- 22370754
TI  - First isolation of Dengue 4 in the state of Sao Paulo, Brazil, 2011.
AB  - We report the first isolation of Dengue virus 4 (DENV-4) in the state of Sao
      Paulo, from two patients - one living in Sao Jose do Rio Preto and the other one
      in Paulo de Faria, both cities located in the Northwest region of the state. The
      virus isolations were accomplished in the clone C6/36 Aedes albopictus cell line,
      followed by indirect immunofluorescence assays, performed with type-specific
      monoclonal antibodies that showed positive reactions for DENV-4. The results were
      confirmed by Nested RT-PCR and Real-Time RT-PCR assays. The introduction of DENV
      4 in a country that already has to deal with the transmission of three other
      serotypes increases the possibility of the occurrence of more severe cases of the
      disease. The importance of early detection of dengue cases, before the virus
      spreads and major outbreaks occur, should be emphasized.

PMID- 22370755
TI  - Hepatitis C virus infection in hemodialysis patients in Maracaibo, Venezuela.
AB  - Over a two year period, the incidence of hepatitis C virus (HCV) infection was
      evaluated in 29 hemodialysis patients, aged between 15 and 75 years (mean +/- SD:
      45 +/- 39.5 years), from the University Hospital Hemodyalisis Unit, Maracaibo,
      Zulia State, Venezuela. Anti-HCV antibodies were determined using a fourth
      generation ELISA (Innotest HCV Ab IV) kit and positive blood samples were tested
      using a recombinant assay kit (Inno-LIA HCV Ab III), both kits from Innogenetics
      N.V., Belgium. The findings indicate a lack of HCV seroconversion in the
      hemodialysis patients over the study period, confirmed by the recombinant assay.
      Risk factors for HCV infection were 0.3270 (95% confidence interval: 0.01323
      8.080) in patients undergoing hemodialysis. The findings suggest a lack of
      significant sources for HCV infection due to the preventive measures to avoid its
      transmission in the hemodialysis unit.

PMID- 22370756
TI  - Review of genitourinary tuberculosis with focus on end-stage renal disease.
AB  - Tuberculosis (TB) is a current public health problem, remaining the most common
      worldwide cause of mortality from infectious disease. Recent studies indicate
      that genitourinary TB is the third most common form of extra-pulmonary disease.
      The diagnosis of renal TB can be hypothesized in a non-specific bacterial
      cystitis associated with a therapeutic failure or a urinalysis with a persistent
      leukocyturia in the absence of bacteriuria. We report on the case of a 33-year
      old man who presented on admission end stage renal disease (ESRD) secondary to
      renal TB and a past history of pulmonary TB with important radiologic findings.
      The diagnosis was based on clinical findings despite all cultures being negative.
      Empiric treatment with tuberculostatic drugs was started and the patient became
      stable. He was discharged with no symptom, but without renal function recovery.
      He is on maintenance hemodialysis three times a week. TB is an important cause of
      kidney disease and can lead to irreversible renal function loss.

PMID- 22370757
TI  - Sonochemical formation of iron oxide nanoparticles in ionic liquids for magnetic
      liquid marble.
AB  - Ionic liquids (ILs)-stabilized iron oxide (Fe(2)O(3)) nanoparticles were
      synthesized by the ultrasonic decomposition of iron carbonyl precursors in
      [EMIm][BF(4)] without any stabilizing or capping agents. The Fe(2)O(3)
      nanoparticles were isolated and characterized by X-ray powder diffraction,
      transmission electron microscopy and susceptibility measurements. The
      physicochemical properties of ILs containing magnetic Fe(2)O(3) nanoparticles
      (denoted as Fe(2)O(3)@[EMIm][BF(4)]), including surface properties, density,
      viscosity and stability, were investigated in detail and compared with that of
      [EMIm][BF(4)]. The Fe(2)O(3)@[EMIm][BF(4)] can be directly used as magnetic ionic
      liquid marble by coating with hydrophobic and unreactive polytetrafluoroethylene
      (PTFE), for which the effective surface tension was determined by the puddle
      height method. The resulting magnetic ionic liquid marble can be transported
      under external magnetic actuation, without detachment of magnetic particles from
      the marble surface that is usually observed in water marble.

PMID- 22370758
TI  - microRNA expression signatures and parallels between monocyte subsets and
      atherosclerotic plaque in humans.
AB  - Small non-coding microRNAs (miRNAs) have emerged to play critical roles in
      cardiovascular biology. Monocytes critically drive atherosclerotic lesion
      formation, and can be subdivided into a classical and non-classical subset. Here
      we scrutinised the miRNA signature of human classical and non-classical
      monocytes, and compared miRNA expression profiles of atherosclerotic plaques from
      human carotid arteries and healthy arteries. We identified miRNAs to be
      differentially regulated with a two-fold or higher difference between classical
      and non-classical monocyte subsets. Moreover, comparing miRNA expression in
      atherosclerotic plaques compared to healthy arteries, we observed several miRNAs
      to be aberrantly expressed, with the majority of miRNAs displaying a two-fold or
      higher increase in plaques and only few miRNAs being decreased. To elucidate
      similarities in miRNA signatures between monocyte subsets and atherosclerotic
      plaque, expression of miRNAs highly abundant in monocytes and plaque tissues were
      compared. Several miRNAs were found in atherosclerotic plaques but not in healthy
      vessels or either monocyte subset. However, we could identify miRNAs co-expressed
      in plaque tissue and classical monocytes (miR-99b, miR-152), or non-classical
      monocytes (miR-422a), or in both monocytes subsets. We thus unravelled candidate
      miRNAs, which may facilitate our understanding of monocyte recruitment and fate
      during atherosclerosis, and may serve as therapeutic targets for treating
      inflammatory vascular diseases.

PMID- 22370759
TI  - Quantifying eye stability during a fixation task: a review of definitions and
      methods.
AB  - Several definitions, measurements, and implicit meanings of 'fixation stability'
      have been used in clinical vision research, leading to some confusion. One
      definition concerns eye movements observed within fixations (i.e., within periods
      separated by saccades) when observing a point target: drift, microsaccades and
      physiological tremor all lead to some degree of within-fixation instability. A
      second definition relates to eye position during multiple fixations (and
      saccades) when patients fixate a point target. Increased between-fixation
      variability, combined with within-fixation instability, is known to be associated
      with poorer visual function in people with retinal disease such as age-related
      macular degeneration. In this review article, methods of eye stability
      measurement and quantification are summarised. Two common measures are described
      in detail: the bivariate contour ellipse area (BCEA) and the within-isolines
      area. The first measure assumes normality of the underlying positions
      distribution whereas the second does not. Each of these measures can be applied
      to two fundamentally different kinds of eye position data collected during a
      period of target observation. In the first case, mean positions of eye fixations
      are used to obtain an estimate of between-fixation variability. In the second
      case, often used in clinical vision research, eye position samples recorded by
      the eyetracker are used to obtain an estimate that confounds within- and between
      fixation variability. We show that these two methods can produce significantly
      different values of eye stability, especially when reported as BCEA values.
      Statistical techniques for describing eye stability when the distribution of eye
      positions is multimodal and not normally distributed are also reviewed.

PMID- 22370760
TI  - Morphometric analyses of retinal sections.
AB  - Morphometric analyses of retinal sections have been used in examining retinal
      diseases. For examples, neuronal cells were significantly lost in the retinal
      ganglion cell layer (RGCL) in rat models with N-methyl-D-aspartate (NMDA)-induced
      excitotoxicity(1), retinal ischemia-reperfusion injury(2) and glaucoma(3). 
      Reduction of INL and inner plexiform layer (IPL) thicknesses were reversed with
      citicoline treatment in rats' eyes subjected to kainic acid-mediated glutamate
      excitotoxicity(4). Alteration of RGC density and soma sizes were observed with
      different drug treatments in eyes with elevated intraocular pressure(3,5,6).
      Therefore, having objective methods of analyzing the retinal morphometries may be
      of great significance in evaluating retinal pathologies and the effectiveness of
      therapeutic strategies.    The retinal structure is multi-layers and several
      different kinds of neurons exist in the retina. The morphometric parameters of
      retina such as cell number, cell size and thickness of different layers are more
      complex than the cell culture system. Early on, these parameters can be detected
      using other commercial imaging software. The values are normally of relative
      value, and changing to the precise value may need further accurate calculation.
      Also, the tracing of the cell size and morphology may not be accurate and
      sensitive enough for statistic analysis, especially in the chronic glaucoma
      model. The measurements used in this protocol provided a more precise and easy
      way. And the absolute length of the line and size of the cell can be reported
      directly and easy to be copied to other files. For example, we traced the margin
      of the inner and outer most nuclei in the INL and formed a line then using the
      software to draw a 90 degree angle to measure the thickness. While without the
      help of the software, the line maybe oblique and the changing of retinal
      thickness may not be repeatable among individual observers. In addition, the
      number and density of RGCs can also be quantified. This protocol successfully
      decreases the variability in quantitating features of the retina, increases the
      sensitivity in detecting minimal changes. This video will demonstrate three types
      of morphometric analyses of the retinal sections. They include measuring the INL
      thickness, quantifying the number of RGCs and measuring the sizes of RGCs in
      absolute value. These three analyses are carried out with Stereo Investigator
      (MBF Bioscience - MicroBrightField, Inc.). The technique can offer a simple but
      scientific platform for morphometric analyses.

PMID- 22370762
TI  - Substance use in young adults with pediatric-onset spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To assess the prevalence of
      substance use in young adults with pediatric-onset spinal cord injury (SCI) and
      its relationship with demographic factors, and medical and psychosocial outcomes.
      SETTING: Young adults living in the United States who received pediatric SCI care
      at one of three SCI programs at the Shriners Hospitals for Children. METHODS:
      Individuals aged 21-25 years who had sustained SCI before the age of 19 were
      interviewed with a structured questionnaire including standardized outcome
      measures: FIM, satisfaction with life scale (SWLS), short-form 12 health survey
      (SF-12), patient health questionnaire-9 (PHQ-9) depression scale, and Craig
      handicap assessment and recording technique (CHART). RESULTS: Sample included 215
      individuals with a mean age at interview of 23.3 (s.d.=0.9) years and mean age at
      injury of 13.2 (s.d.=4.9) years. In all, 24% had a college degree, 36% were
      employed and 12% were married. Regular substance use was reported by 28% for
      tobacco, 55% for alcohol and 11% for marijuana. Tobacco use was associated with
      depressive symptoms and unemployment; alcohol use was associated with having a
      college degree, single status and independent mobility; and marijuana use was
      associated with not having a college degree. There were no significant
      associations between substance use and injury-related factors or life
      satisfaction. CONCLUSION: Substance use in young adults with pediatric-onset SCI
      was associated with factors such as education, employment, marital status and
      depressive symptoms. Clinicians caring for youth with SCI should counsel patients
      and caregivers regarding the use of substances and potential associations with
      outcomes in adulthood.

PMID- 22370763
TI  - Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell
      development.
AB  - Runx transcription factor family proteins have essential roles during T-cell
      development by either activating or repressing target genes. For instance,
      lineage- and stage-specific expression of Cd4 and ThPOK is controlled by a
      transcriptional silencer embedded in each locus, whose activity requires bindings
      of Runx complexes. The evolutionarily conserved VWRPY penta-peptide sequences in
      Runx proteins have been shown to be responsible for repressive function as a
      platform to recruit Groucho/TLE transcriptional corepressors. However, it remains
      elusive whether requirement for the VWRPY motif differs among Runx target genes.
      By examining mice lacking VWRPY motifs in both Runx1 and Runx3 proteins, here, we
      show a full and partial derepression of Cd4 and ThPOK in CD8-linegae T cells,
      respectively. Thus, whereas Cd4 silencing completely depends on the VWRPY motif,
      both VWRPY-dependent and -independent mechanisms operate to repress ThPOK gene.
      These results indicate that Runx proteins utilize different modes to repress
      expression of different target genes.

PMID- 22370764
TI  - Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans.
AB  - BACKGROUND: Excessive oxidative stress plays a causal role in various diseases
      such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is
      a pathological condition associated with excess growth hormone (GH) and insulin
      like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension,
      atherosclerosis, and heart failure; resulting in premature death. We hypothesized
      that these conditions may be associated with increased oxidative stress.
      OBJECTIVE AND METHODS: We explored the oxidative stress levels in the serum and
      tissues of GH-transgenic rats as an animal model for acromegaly. We also measured
      the oxidative stress levels in the serum of patients with acromegaly and age-,
      sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I
      on reactive oxygen species (ROS) production in C2C12 myocytes. RESULTS: The
      levels of an oxidative stress marker, serum thiobarbituric acid reactive
      substances (TBARS) were increased in the GH-transgenic rats. Further, tissue
      oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth
      muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS
      levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in
      acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes
      in vitro. CONCLUSIONS: These data indicate that the increased levels of IGF-I are
      associated with enhanced oxidative stress in rats and humans. In addition,
      increased ROS may play an important role in the complications and premature death
      in acromegaly.

PMID- 22370765
TI  - Predicting high risk adolescents' substance use over time: the role of parental
      monitoring.
AB  - We examined whether parental monitoring at baseline predicted subsequent
      substance use in a high-risk youth population. Students in 14 alternative high
      schools in Washington State completed self-report surveys at three time points
      over the course of 2 years. Primary analyses included 1,423 students aged 14-20
      who lived with at least one parent or step-parent at baseline. Using hierarchical
      linear modeling, we found that high parental monitoring at baseline predicted
      significantly less use of alcohol, marijuana, downers, cocaine, PCP, LSD, and
      prescription drugs and drinking to intoxication at the first posttest.
      Approximately 1 year later, high parental monitoring at baseline predicted
      significantly less use of alcohol, cocaine, prescription drugs, uppers, and
      ecstasy and drinking to intoxication. Study results suggest that parental
      monitoring serves as a protective factor, even for high-risk alternative high
      school students. Including a parental monitoring component may increase the
      effectiveness of traditional drug prevention programs.

PMID- 22370766
TI  - Primary care physician perceptions on caring for complex patients with medical
      and mental illness.
AB  - BACKGROUND: Mental illness is common and associated with poor outcomes for co
      occurring medical illness. Since primary care physicians manage the treatment of
      complex patients with both mental and medical illnesses, their perspectives on
      the care of these patients is vital to improving clinical outcomes. OBJECTIVE: To
      examine physician perceptions of patient, physician and system factors that
      affect the care of complex patients with mental and medical illness. DESIGN:
      Inductive, participatory, team-based qualitative analysis of transcripts of in
      depth semi-structured interviews. PARTICIPANTS: Fifteen internal medicine
      physicians from two university primary care clinics and three community health
      clinics. RESULTS: Participant characteristics were balanced in terms of years in
      practice, practice site, and gender. Physicians identified contributing factors
      to the complexity of patient care within the domains of patient, physician and
      system factors. Physicians identified 1) type of mental illness, 2) acuity of
      mental illness, and 3) communication styles of individual patients as the
      principal patient characteristics that affected care. Physicians expressed
      concern regarding their own lack of medical knowledge, clinical experience, and
      communication skills in treating mental illness. Further, they discussed tensions
      between professionalism and emotional responses to patients. Participants
      expressed great frustration with the healthcare system centered on: 1) lack of
      mental health resources, 2) fragmentation of care, 3) clinic procedures, and 4)
      the national healthcare system. CONCLUSIONS: Physicians in this study made a
      compelling case for increased training in the treatment of mental illness and
      improvements in the delivery of mental health care. Participants expressed a
      strong desire for increased integration of care through collaboration between
      primary care providers and mental health specialists. This approach could improve
      both comfort in treating mental illness and the delivery of care for complex
      patients.

PMID- 22370767
TI  - Decision-making process reported by Medicare patients who had coronary artery
      stenting or surgery for prostate cancer.
AB  - BACKGROUND: Patients facing decisions should be told about their options, have
      the opportunity to discuss the pros and cons, and have their preferences
      reflected in the final decision. OBJECTIVES: To learn how decisions were made for
      two major preference-sensitive interventions. DESIGN: Mail survey of probability
      samples of patients who underwent the procedures. PARTICIPANTS: Fee-for-service
      Medicare beneficiaries who had surgery for prostate cancer or elective coronary
      artery stenting in the last half of 2008. MAIN MEASUREMENTS: Patients' reports of
      which options were presented for serious consideration, the amount of discussion
      of the pros and cons of the chosen option, and if they were asked about their
      preferences. RESULTS: The majority (64%) of prostate cancer surgery patients
      reported that at least one alternative to surgery was presented as a serious
      option. Almost all (94%) said they and their doctors discussed the pros, and 63%
      said they discussed the cons of surgery "a lot" or "some". Most (76%) said they
      were asked about their treatment preferences. Few who received stents said they
      were presented with options to seriously consider (10%). While most (77%)
      reported talking with doctors about the reasons for stents "a lot" or "some", few
      (19%) reported talking about the cons. Only 16% said they were asked about their
      treatment preferences. CONCLUSIONS: While prostate cancer surgery patients
      reported more involvement in decision making than elective stent patients, the
      reports of both groups document the need for increased efforts to inform and
      involve patients facing preference-sensitive intervention decisions.

PMID- 22370768
TI  - The role of primary care physicians in improving colorectal cancer screening in
      patients with HIV.
AB  - BACKGROUND: As HIV positive patients live longer, they become susceptible to the
      development of non-AIDS defining malignancies. Little is known about routine
      cancer screening practices in that population and the factors associated with
      cancer screening. OBJECTIVE: Evaluate 1) the proportion of patients with HIV who
      had any type of colorectal cancer (CRC) screening and 2) whether having a primary
      care physician (PCP) or seeking care in an integrated care practice is associated
      with higher CRC screening. DESIGN: A cross-sectional chart abstraction study of
      patients with HIV enrolled in the Philadelphia Medical Monitoring Project (MMP).
      PARTICIPANTS: MMP participants age 50 and older. MAIN MEASURES: CRC screening
      defined as having a documented colonoscopy, sigmoidoscopy, barium enema, or fecal
      occult blood test after the age of 50. KEY RESULTS: Out of 123 chart abstractions
      performed, 115 had a complete clinical record from MMP. The majority of the
      population was male (71.3%), Black/Hispanic (73.8%) and between the age of 50 and
      59 (71.3%). 45.2% of patients did not have a PCP. The overall proportion of
      patients who received CRC screening was 46.9%. Having a documented PCP was the
      only factor strongly associated with CRC screening. Rates of screening were 66.7%
      among those with a PCP versus 28.5% among those without a PCP (chi(2) p < 0.001).
      After adjusting for race, socioeconomic status, substance and alcohol abuse, the
      odds of getting CRC screening in those with a PCP was 4.59 (95% CI 2.01-10.48, p
      < 0.001). The type of practice where patients were enrolled into care was not
      associated with CRC screening. CONCLUSIONS: Having a PCP significantly increases
      the likelihood of receiving CRC screening in patients with HIV. Competency in
      addressing primary care needs in HIV clinics will only become more important as
      patients with HIV age.

PMID- 22370769
TI  - Teaching motivational interviewing to primary care staff in the Veterans Health
      Administration.
AB  - BACKGROUND: The Veterans Health Administration (VHA) is implementing the patient
      centered medical home (PCMH) model of primary care which emphasizes patient
      centered care and the promotion of healthy lifestyle changes. Motivational
      Interviewing (MI) is effective for promoting various health behaviors, thus a
      training protocol for primary care staff was implemented in a VHA health care
      setting. OBJECTIVES: We examined the effect of the training protocol on MI
      knowledge, confidence in ability to use MI-related skills and apply them to
      written vignettes, perceived comfort level and skill in lifestyle counseling, and
      job-related burnout. DESIGN: Training was provided by experts in MI. The training
      protocol consisted of three sessions--one half day in-person workshop followed by
      a 60-minute virtual training, followed by a second workshop. Each of the sessions
      were spaced two weeks apart and introduced trainees to the theory, principles,
      and skills of using MI in health care settings. PARTICIPANTS: All primary care
      staff at the Veterans Affairs Palo Alto Health Care System were invited to
      participate. MEASUREMENTS: Trainees completed a short set of questionnaires
      immediately before and immediately after the training. RESULTS: We found support
      for our primary hypotheses related to knowledge, confidence, and written
      responses to the vignettes. Changes in perceived comfort level and skill in
      lifestyle counseling, and job-related burnout were not observed. CONCLUSIONS:
      Training primary care staff in MI is likely to become increasingly common as
      health care systems transition to the PCMH model of care. Therefore, it is
      important for health care systems to have low-cost methods for evaluating the
      effectiveness of such trainings. This study is a first step in developing a brief
      written assessment with the potential of measuring change in a range of behaviors
      and skills consistent with MI.

PMID- 22370770
TI  - Newer anticoagulants in cardiovascular disease: a systematic review of the
      literature.
AB  - Vitamin K antagonists (VKAs) such as warfarin have traditionally been the major
      therapeutic option for anticoagulation in clinical practice. VKAs are effective
      and extensively recommended for the prevention of venous and arterial
      thromboembolism in cardiovascular disease. Despite its effectiveness, warfarin is
      limited by factors such as a narrow therapeutic index, drug-drug interactions,
      food interactions, slow onset and offset of action, hemorrhage, and routine
      anticoagulation monitoring to maintain therapeutic international normalized
      ratio. During the last 2 decades, the approval of anticoagulants, such as low
      molecular-weight heparins, indirect factor Xa inhibitors (eg, fondaparinux), and
      direct thrombin inhibitors (eg, argatroban, lepirudin, and desirudin), have
      expanded the number of available antithrombotic compounds with additional targets
      within the anticoagulation pathway. Although these medications offer several
      potential therapeutic advantages, they all require parenteral or subcutaneous
      administration and are substantially more expensive than VKAs. Thus, VKAs,
      despite several limitations, have remained the major option for most patients
      requiring chronic anticoagulation. These limitations have prompted interest in
      the development of newer oral anticoagulants. Novel anticoagulants targeting
      inhibition of factor Xa and thrombin (factor IIa) have now been incorporated into
      clinical practice based on the results of large randomized clinical trials, with
      the recent U.S. Food and Drug Administration approval of dabigatran for stroke
      prevention in atrial fibrillation and rivaroxaban for deep vein thrombosis and
      stroke prevention in atrial fibrillation, with multiple other agents in various
      stages of development for these and other indications. This review discusses the
      pharmacological properties, clinical results, and therapeutic applications of
      novel and new anticoagulants, thereby providing an outline for the future of
      anticoagulation in cardiovascular disease.

PMID- 22370772
TI  - A new feature for Cardiology in Review.

PMID- 22370773
TI  - Current status of biology, bioengineering, and therapeutic potential of stem
      cells.

PMID- 22370774
TI  - Multi-targeted hybrids based on HDAC inhibitors for anti-cancer drug discovery.
AB  - Multi-targeted hybrids combine two drugs in a single molecule to have greater
      medicinal effects than its individual components. Recently, a number of anti
      cancer drug candidates such as CUDC-101 (Curis) have been designed based on
      linking properly two selected pharmacophores endowed with activity against
      different therapeutic targets.

PMID- 22370775
TI  - Perspectives on mesenchymal stem cells: tissue repair, immune modulation, and
      tumor homing.
AB  - Mesenchymal stem cells (MSCs) or MSC-like cells have been identified in a variety
      of different tissues that share molecular expression profiles and biological
      functions but also retain a unique differentiation preference depending on their
      tissue origins. MSCs play beneficial roles in the healing of damaged tissue by
      directly differentiating to many different resident cell types and/or by
      secreting several trophic factors that aid tissue repair. Aside from MSCs'
      reparative stem cell function, they drive immune responses toward
      immunosuppression and anti-inflammation. This novel function of MSCs opens up new
      avenues for clinical development of MSC immune-therapeutics to treat
      uncontrollable, life threatening, severe, chronic inflammation and autoimmune
      disease. Unexpectedly high rates of MSCs' tumor homing capacity and their tumor
      supporting capability have also been noted in tumor-bearing animal models. In
      this review, we will discuss MSCs' basic cell biology and perspectives on MSCs in
      terms of tissue repair, immune modulation, and tumor homing.

PMID- 22370776
TI  - Immunomodulatory properties of mesenchymal stem cells and their therapeutic
      applications.
AB  - Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most
      adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung,
      skeletal muscle and kidney. The term MSC is currently being used to represent
      both mesenchymal stem cells and multipotent mesenchymal stromal cells. Numerous
      reports on systemic administration of MSCs leading to functional improvements
      based on the paradigm of engraftment and differentiation have been published.
      However, it is not only difficult to demonstrate extensive engraftment of cells,
      but also no convincing clinical results have been generated from phase 3 trials
      as of yet and prolonged responses to therapy have been noted after identification
      of MSCs had discontinued. It is now clear that there is another mechanism by
      which MSCs exert their reparative benefits. Recently, MSCs have been shown to
      possess immunomodulatory properties. These include suppression of T cell
      proliferation, influencing dendritic cell maturation and function, suppression of
      B cell proliferation and terminal differentiation, and immune modulation of other
      immune cells such as NK cells and macrophages. In terms of the clinical
      applications of MSCs, they are being tested in four main areas: tissue
      regeneration for cartilage, bone, muscle, tendon and neuronal cells; as cell
      vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment;
      and treatment of immune diseases such as graft-versus-host disease, rheumatoid
      arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis
      and multiple sclerosis. In this review, the mechanisms of immunomodulatory
      effects of MSCs and examples of animal and clinical uses of their
      immunomodulatory effects are described.

PMID- 22370777
TI  - Dysfunction of endothelial progenitor cells under diabetic conditions and its
      underlying mechanisms.
AB  - Cardiovascular complications have been major concerns in the treatment of
      diabetes, and up to 80% of all deaths in diabetic patients are linked to
      cardiovascular problems. Impaired angiogenesis is one of the most serious
      symptoms associated with diabetes, resulting in delayed wound healing and lower
      limb amputation. Endothelial progenitor cells (EPCs), a subpopulation of adult
      stem cells, are recruited from bone marrow to the injured vessel to promote
      endothelial regeneration and neovascularization, playing an important role in
      angiogenesis. Interestingly, several clinical studies have showed that the number
      of recruited EPCs is reduced and their function is decreased under diabetic
      conditions, implying that diabetic EPC dysfunction may contribute to defective
      angiogenesis and resultant cardiovascular complications in diabetes. To recover
      the functional abilities of diabetic EPCs and to address possible application of
      EPC cell therapy to diabetic patients, some studies provided explanations for
      diabetic EPC dysfunction including increased oxidative stress, involvement of the
      inflammatory response, alteration in the nitric oxide pathway and reduced signals
      for EPC recruitment. This review discusses clinical evidence of impairment of EPC
      functions under diabetic conditions and the suggested mechanisms for diabetic EPC
      dysfunction.

PMID- 22370778
TI  - Oncogenic challenges in stem cells and the link to cancer initiation.
AB  - Adult stem cells, which are characterized by self-renewal and multi-potency, are
      classified as specialized cell types, responsible for the regeneration of damaged
      tissues. There is growing evidence that senescence of stem cells (or stem cell
      aging) is closely associated with a variety of aging-related diseases such as
      tissue atrophy, degenerative diseases and onset of cancers. Alterations in the
      systemic environment during aging may trigger stress signaling in stem cells and
      reduce stem cell characteristics, resulting in loss of differentiation potential
      and defective self-renewal (referred to as mal-differentiation). Thus, it has
      been suggested that aging-related disorders such as retarded regeneration of
      damaged tissue and onset of cancer may result from the mal-differentiation of
      stem cells. In particular, many types of cancers such as leukemia, intestinal
      cancer, skin cancer and sarcoma have been shown to originate from adult stem
      cells after a variety of oncogenic challenges. This review summarizes recent
      studies on cancers originating from stem cells, demonstrating possible molecular
      mechanisms that govern the susceptibility of stem cells to oncogenic challenges.

PMID- 22370779
TI  - Induced pluripotent stem cell research: a revolutionary approach to face the
      challenges in drug screening.
AB  - Discovery of induced pluripotent stem (iPS) cells in 2006 provided a new path for
      cell transplantation and drug screening. The iPS cells are stem cells derived
      from somatic cells that have been genetically reprogrammed into a pluripotent
      state. Similar to embryonic stem (ES) cells, iPS cells are capable of
      differentiating into three germ layers, eliminating some of the hurdles in ES
      cell technology. Further progress and advances in iPS cell technology, from viral
      to non-viral systems and from integrating to non-integrating approaches of
      foreign genes into the host genome, have enhanced the existing technology, making
      it more feasible for clinical applications. In particular, advances in iPS cell
      technology should enable autologous transplantation and more efficient drug
      discovery. Cell transplantation may lead to improved treatments for various
      diseases, including neurological, endocrine, and hepatic diseases. In studies on
      drug discovery, iPS cells generated from patient-derived somatic cells could be
      differentiated into specific cells expressing specific phenotypes, which could
      then be used as disease models. Thus, iPS cells can be helpful in understanding
      the mechanisms of disease progression and in cell-based efficient drug screening.
      Here, we summarize the history and progress of iPS cell technology, provide
      support for the growing interest in iPS cell applications with emphasis on
      practical uses in cell-based drug screening, and discuss some challenges faced in
      the use of this technology.

PMID- 22370780
TI  - Humanized murine model for HBV and HCV using human induced pluripotent stem
      cells.
AB  - Infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) results in
      heterogeneous outcomes from acute asymptomatic infection to chronic infection
      leading to cirrhosis and hepatocellular carcinoma (HCC). In vitro models using
      animal hepatocytes, human HCC cell lines, or in vivo transgenic mouse models have
      contributed invaluably to understanding the pathogenesis of HBV and HCV. A
      humanized mouse model made by reconstitution of human primary hepatocytes in the
      liver of the immunodeficient mouse provides a novel experimental opportunity
      which mimics the in vivo growth of the human hepatocytes. The limited access to
      primary human hepatocytes necessitated the search for other cellular sources,
      such as pluripotent stem cells. Human embryonic stem cells (hESCs) have the
      features of self-renewal and pluripotency and differentiate into cells of all
      three germ layers, including hepatocytes. Humaninduced pluripotent stem cells
      (iPSCs) derived from the patient's or individual's own cells provide a novel
      opportunity to generate hepatocyte-like cells with the defined genetic
      composition. Here, we will review the current perspective of the models used for
      HBV and HCV study, and introduce the personalized mouse model using human iPSCs.
      This novel mouse model will facilitate the direct investigation of HBV and HCV in
      human hepatocytes as well as probing the genetic influence on the susceptibility
      of hepatocytes to HBV and HCV.

PMID- 22370781
TI  - Amniotic fluid-derived stem cells in regenerative medicine research.
AB  - The stem cells isolated from amniotic fluid present an exciting possible
      contribution to the field of regenerative medicine and amniotic fluid-derived
      stem (AFS) cells have significant potential for research and therapeutic
      applications. AFS cells are multipotent, showing the ability to differentiate
      into cell types from all three embryonic germ layers. They express both embryonic
      and adult stem cell markers, expand extensively without feeder cells, double in
      36 h, and are not tumorigenic. The AFS cells can be maintained for over 250
      population doublings and preserve their telomere length and a normal karyotype.
      They differentiate easily into specific cell lineages and do not require human
      embryo tissue for their isolation, thus avoiding the current controversies
      associated with the use of human embryonic stem (ES) cells. The discovery of the
      AFS cells has been recent, and a great deal of work remains to be performed on
      the characterization and use of these cells. This review describes the various
      differentiated lineages that AFS cells can form and the future of these promising
      new stem cells in regenerative medicine research.

PMID- 22370782
TI  - Chemical biology in stem cell research.
AB  - Stem cells are offering a considerable range of prospects to the biomedical
      research including novel platforms for disease models and drug discovery tools to
      cell transplantation and regenerative therapies. However, there are several
      obstacles to overcome to bring these potentials into reality. First, robust
      methods to maintain stem cells in the pluripotent state should be established and
      factors that are required to direct stem cell fate into a particular lineage
      should be elucidated. Second, both allogeneic rejection following transplantation
      and limited cell availability issues must be circumvented. These challenges are
      being addressed, at least in part, through the identification of a group of
      chemicals (small molecules) that possess novel activities on stem cell biology.
      For example, small molecules can be used both in vitro and/or in vivo as tools to
      promote proliferation of stem cells (self-renewal), to direct stem cells to a
      lineage specific patterns (differentiation), or to reprogram somatic cells to a
      more undifferentiated state (de-differentiation or reprogramming). These
      molecules, in turn, have provided new insights into the signaling mechanisms that
      regulate stem cell biology, and may eventually lead to effective therapies in
      regenerative medicine. In this review, we will introduce recent findings with
      regards to small molecules and their impact on stem cell self-renewal and
      differentiation.

PMID- 22370783
TI  - Potential of engineering methodologies for the application to pharmaceutical
      research.
AB  - Current engineering methods and their potential for use in cell-based research
      are reviewed. The basis of the suggested engineering methods is that real
      cellular responses can be assessed when the cells are under the same conditions
      as in vivo. Providing various conditions for this various engineering
      methodologies can be adopted. Three major factors should be considered when we
      apply bio-mimetic conditions to cells under in vitro culture conditions. They are
      the surface pattern and stiffness of the substrate, physical stimuli and
      neighboring cells. Various outcomes affected by those factors are introduced and
      reviewed. In particular, those outcomes from stem cell research have been
      reported. Even though some limitations of adopting those factors alone or
      combined still exist, the potential is now widely being recognized. The readers
      are kindly asked to consider those methodologies in relation to pharmaceutical
      research.

PMID- 22370784
TI  - Peniciside, a new triterpenoid glycoside, from the fungus Penicillium sp. 169.
AB  - Peniciside, a new fernene triterpenoid glycoside, was isolated from the EtOAc
      extract of the solid-state fermented rice culture of the fungus Penicillium sp.
      169. Its structure was elucidated on the basis of spectroscopic analysis, and the
      absolute configuration was determined by X-ray crystallographic analysis and
      chemical methods. Peniciside is the first example of a fernene triterpenoid
      glycoside with two hydroxyls at C-19 and C-20.

PMID- 22370785
TI  - Phenylpropanoid ester from Zingiber officinale and their inhibitory effects on
      the production of nitric oxide.
AB  - A new phenylpropanoid ester mixture, (E)-geranylferulic acid (1a) and (Z)
      geranylferulic acid (1b), along with 13 known compounds, [6]-gingerol (2), [8]
      gingerol (3), [10]-gingerdione (4), 1-dehydro-[6]-gingerdione (5), 1-dehydro-[8]
      gingerdione (6), [6]-paradol (7), [8]-paradol (8), [6]-gingeroldiacetate (9), 6
      hydroxy-[6]-shogaol (10), galanolactone (11), trans-(r)-sesquiphellandrol (12),
      trans-sesquipiperitol (13), and 4alpha,5beta-dihydroxybisabola-2,10-diene (14)
      were isolated from ethanol extract of Zingiber officinale. Their structures were
      determined based on the spectroscopic (1D, 2D-NMR and MS) and chemical evidence.
      All of the isolates were evaluated for their potential to inhibit LPS-induced
      production of nitric oxide in murine macrophage RAW264.7 cells. Compounds 1-12
      were found to inhibit nitric oxide production with IC(50) values ranging from 5.5
      to 28.5 MUM.

PMID- 22370786
TI  - Chain branching approach in structure modification of TRPV1 receptor antagonist
      MK056 and its analogs.
AB  - A series of chain branched 1,3-dibenzylthiourea derivatives were designed,
      synthesized, and evaluated for their antagonist activity against TRPV1. The
      synthesized chain branched 1,3-dibenzylthioureas 9a-g were tested for their
      antagonist activities against TRPV1 by (45)Ca(2+)-influx assay using neonatal rat
      cultured spinal sensory neurons. Fluorinated ethyl-branched analog 9g showed the
      most potent antagonist activity with an IC(50) value of 0.41 MUM, but all of the
      chain branched analogs were less potent than the parent compounds MK-056 and SC
      0030, indicating that chain branching on the benzylic position of B-ring is
      detrimental to potency. Optimized receptor binding seems to be interfered by
      chain branching, and resulted in decrease in potency.

PMID- 22370787
TI  - Novel iridoids from the flowers of Campsis grandiflora.
AB  - A non-glycosidic iridoid, campsinol (1), and two iridoid glucosides, 7-O-(Z)-p
      coumaroylcachineside V (2) and 7-O-(E)-p-coumaroylcachineside I (3), were
      isolated from the fresh flowers of Campsis grandiflora along with five known
      iridoid glycosides, ixoroside (4), campsiside (5), cachineside I (6), 5
      hydroxycampenoside (7), and 5-hydroxycampsiside (8), and two known
      phenylpropanoid glycosides, acteoside (9) and leucosceptoside A (10). The
      structures of these compounds were determined based on the NMR and Mass
      spectroscopic data and other chemical evidences.

PMID- 22370788
TI  - Anti-glioma effect and safety of docetaxel-loaded nanoemulsion.
AB  - Docetaxel, an inhibitor of microtubule depolymerization, has been used for many
      malignancies. Due to its toxicity and the non-selective distribution of its
      commercial formulation, Taxotere(r), new formulations with less toxicity and
      tumor targeting need to be explored. For its safety and ease of factory scale
      production, nanoemulsion, was selected to encapsulate docetaxel. The particle
      size of docetaxel loaded nanoemulsion (DNE) was 72.3 nm, the average zeta
      potential was -6.38 mV, the encapsulation efficiency was 93.1% and the drug
      loading capacity was 2.87%. Although DNE presented similar antiproliferation
      effects on both U87 cells and bEnd.3 cells, its in vivo toxicity was
      significantly lower than Taxotere(r). In vivo fluorescent imaging suggested
      nanoemulsions loaded with a fluorescent probe could distribute to the brain and
      accumulate at the glioma site. The pharmacological experiments also confirmed
      that the DNE could target glioma sites and prolong the median survival time of
      mice with gliomas. In conclusion, DNE is a new, less toxic, drug formulation that
      is effective for brain glioma therapy.

PMID- 22370790
TI  - Content uniformity in granules for aceclofenac controlled release (CR) tablets
      determined using near-infrared spectroscopy and wide area illumination (WAI)
      Raman spectroscopy.
AB  - Non-destructive and rapid determination methods were developed for aceclofenac
      controlled release (CR) tablets. The tablet is composed of two layers, rapid
      release and controlled release (CR) layers. The pharmaceutical manufacturing
      process for CR granules is very critical for dissolution control of CR tablets.
      During processing, a rapid and nondestructive method to test content uniformity
      of aceclofenac granules is required. Chemometrics using near-infrared (NIR) and
      Raman spectroscopy have found significant uses in quantitative analysis of
      pharmaceutical products in complex matrixes. Most of the pharmaceutical products
      can be measured directly with little or no sample preparation using these
      spectroscopic methods. This study showed NIR and wide area illumination Raman
      spectroscopy with partial least squares (PLS) was very effective for the content
      uniformity of granules while high performance liquid chromatography (HPLC), a
      conventional method, was time-consuming and ineffective for real time control.
      This study showed that on-line control of content uniformity control of
      aceclofenac CR tablets can be achieved using NIR and Raman spectroscopy.

PMID- 22370789
TI  - Synthesis and characterization of G5 PAMAM dendrimer containing daunorubicin for
      targeting cancer cells.
AB  - A multifunctional dendritic nanodevice containing folate (FA) as the targeting
      molecule and daunorubicin (DNR) as the chemotherapeutic drug has been designed
      and synthesized. The primary amino groups on the surface of the generation 5
      poly(amidoamine) dendrimer (G5 dendrimer) were acetylated partially. FA and DNR
      were conjugated to the remaining primary amino groups on the G5 dendrimer through
      amide and ester linkage, respectively, to generate the difunctional dendritic
      device. The synthetic approach of G5 PAMAM dendrimer containing daunorubicin and
      folic acid would be useful for targeting the overexpressed membrance-associated
      folate receptors of KB human carcinoma cell line and discreating them
      effectively.

PMID- 22370791
TI  - The influence of stabilizer and bioadhesive polymer on the permeation-enhancing
      effect of AT1002 in the nasal delivery of a paracellular marker.
AB  - Permeation enhancers are of major interest to improve the low bioavailability of
      therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid
      fragment of Zonula occludens toxin, was reported to possess permeation-enhancing
      effects. However, further studies were suggested to focus on the peptide nature
      of AT1002 like stability and membrane clearance to accurately reflect its
      permeation-enhancing potential. Thus, this paper focused on the susceptibility of
      AT1002 for identifying additives to minimize the instability of AT1002, and the
      permeation-enhancing effect of AT1002 when co-administered with a bioadhesive
      polymer. The stability study showed that AT1002 were unstable in neutral to basic
      pH conditions and with increasing incubation time, and 5% dextrose and the 1%
      mixture of amino acids (arginine, cysteine, glycine) significantly minimized the
      instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the
      intranasal study of a paracellular marker, the administration of mannitol with
      AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17
      fold increases in C(max) and AUC(0-360min) in the presence of carrageenan over
      the control. Thus, the addition of carrageenan as a bioadhesive polymer and
      dextrose as a stabilizer together with AT1002 may allow the development of the
      mucosal drug delivery of low-bioavailability therapeutic agents.

PMID- 22370792
TI  - Enhancement of pentobarbital-induced sleep by apigenin through chloride ion
      channel activation.
AB  - This experiment was performed to investigate whether apigenin has hypnotic
      effects and/or enhances pentobarbital-induced sleep behaviors through the
      GABAergic systems. Apigenin prolonged sleep time induced by pentobarbital similar
      to muscimol, a GABA(A) receptors agonist. Apigenin also increased sleep rate and
      sleep time in the combined administration with pentobarbital at the sub-hypnotic
      dosage, and showed synergic effects with muscimol in potentiating sleep onset and
      enhancing sleep time induced by pentobarbital. In addition, both of apigeinin and
      pentobarbital increased chloride influx in primary cultured cerebellar granule
      cells. Apigenin increased glutamate decarboxylase (GAD) and had no effect on the
      expression of GABA(A) receptor alpha-, beta-, gamma-subunits in n hippocampus of
      mouse brain, showing different expression of subunits from pentobarbital
      treatment group. In conclusion, it is suggested that apigenin augments
      pentobarbital-induced sleep behaviors through chloride ion channel activation.

PMID- 22370793
TI  - Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2
      cytokine production.
AB  - Aging is associated with immune dysfunction and conditions such as inflamm-aging
      and immunosuppression. Arsenic, an environmental contaminant distributed
      worldwide, affects the immune system. This study tested the hypothesis that
      arsenic has distinct effects on T cell proliferation and the production of
      cytokines by activated T cells. Murine splenocytes from young (2 months) and aged
      (24-26 months) C57BL/6 mice were exposed to arsenite (As(3+)), the most toxic
      form of inorganic arsenic, and stimulated with concanavalin A (Con A) or anti-CD3
      antibody. T cell proliferation decreased significantly in response to Con A and
      anti-CD3 at subtoxic doses of arsenite in splenocytes from both young and aged
      mice. Arsenite, added concurrently with Con A or anti-CD3, significantly
      inhibited the production of interleukin-2 (IL-2), interferon-gamma (IFN-gamma),
      and interleukin-4 (IL-4) by splenocytes from young mice and significantly reduced
      the production of IL-10 by splenocytes from aged mice. In contrast, the
      production of IL-2 and IL-4 by splenocytes from aged mice was only slightly
      affected by arsenite. The results show that arsenic exposure reduces the immune
      response in splenocytes. Moreover, this effect may be influenced by aging.

PMID- 22370794
TI  - Optimum scratch assay condition to evaluate connective tissue growth factor
      expression for anti-scar therapy.
AB  - To evaluate a potential anti-scar therapy, we first need to have a reliable in
      vitro wound model to understand dermal fibroblast response upon cell injury and
      how cytokine levels are changed upon different wound heal phases. An in vitro
      wound model with different scratch assay conditions on primary human foreskin
      fibroblast monolayer cultures was prepared and cytokine levels and growth
      properties were evaluated with the aim of determining optimum injury conditions
      and observation time. Morphological characteristics of differently scratched
      fibroblasts from 0 to 36 h post injury (1 line, 2 lines and 3 lines) were
      investigated. The expression of connective tissue growth factor, CTGF, which is a
      key mediator in hyper-tropic scarring, and relative intensity of CTGF as a
      function of time were determined by western blot and gelatin Zymography. After
      injury (1 line), CTGF level was increased more than 2-fold within 1 h and
      continuously increased up to 3-fold at 6 h and was leveled down to reach normal
      value at 36 h, at which cell migration was complete. In more serious injury (2
      lines), higher expression of CTGF was observed. The down regulation of CTGF
      expression after CTGF siRNA/lipofectamine transfection in control, 1 line and 2
      lines scratch conditions were 40%, 75% and 55%, respectively. As a model anti
      CTGF based therapy, CTGF siRNA with different ratios of linear polyethyleneimine
      (PEI) complexes (1:1, 1:5, 1:10, 1:20 and 1:30) were prepared and down-regulation
      efficacy of CTGF was evaluated with our optimized scratch assay, which is 1 line
      injury at 6 h post injury observation time. As the cationic linear PEI ratio
      increased, the down regulation efficacy was increased from 20% (1:20) to 55%
      (1:30). As CTGF level was increased to the highest at 6 h and leveled down
      afterwards, CTGF level at 6 h could provide the most sensitive response upon CTGF
      siRNA transfection. The scratch assay in the present study can be employed as a
      useful experimental tool to differentiate between anti-scar therapies for their
      down regulation efficacy of CTGF.

PMID- 22370795
TI  - Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint
      tissue derived stem cells.
AB  - Hydrostatic pressure (HP) is a key component of the in vivo joint environment and
      has been shown to enhance chondrogenesis of stem cells. The objective of this
      study was to investigate the interaction between HP and TGF-beta3 on both the
      initiation and maintenance of a chondrogenic phenotype for joint tissue derived
      stem cells. Pellets generated from porcine chondrocytes (CCs), synovial membrane
      derived stem cells (SDSCs) and infrapatellar fat pad derived stem cells (FPSCs)
      were subjected to 10 MPa of cyclic HP (4 h/day) and different concentrations of
      TGF-beta3 (0, 1 and 10 ng/mL) for 14 days. CCs and stem cells were observed to
      respond differentially to both HP and TGF-beta3 stimulation. HP in the absence of
      TGF-beta3 did not induce robust chondrogenic differentiation of stem cells. At
      low concentrations of TGF-beta3 (1 ng/mL), HP acted to enhance chondrogenesis of
      both SDSCs and FPSCs, as evident by a 3-fold increase in Sox9 expression and a
      significant increase in glycosaminoglycan accumulation. In contrast, HP had no
      effect on cartilage-specific matrix synthesis at higher concentrations of TGF
      beta3 (10 ng/mL). Critically, HP appears to play a key role in the maintenance of
      a chondrogenic phenotype, as evident by a down-regulation of the hypertrophic
      markers type X collagen and Indian hedgehog in SDSCs irrespective of the cytokine
      concentration. In the context of stem cell based therapies for cartilage repair,
      this study demonstrates the importance of considering how joint specific
      environmental factors interact to regulate not only the initiation of
      chondrogenesis, but also the development of a stable hyaline-like repair tissue.

PMID- 22370796
TI  - Changes in embryonic stem cell colony morphology and early differentiation
      markers driven by colloidal crystal topographical cues.
AB  - The use of materials properties to guide cell behaviour is an attractive option
      for regenerative medicine, where controlling stem cell behaviour is important for
      the establishment of a functioning cell population. A wide range of materials
      properties have been shown to influence many types of cells but little is known
      about the effects of topography on embryonic stem cells (ESCs). In order to
      advance this knowledge, we synthesised and characterised substrates formed of
      silica colloidal crystal (SCC) microspheres to present highly ordered and
      reproducible topographical features from 120-600 nm in diameter. We found that,
      compared to cells cultured on flat glass, cells cultured on the SCC substrates
      retained transcription of stem cell (Dppa5a, Nanog, and Pou5f1) and endoderm
      (Afp, Gata4, Sox17, and Foxa2) markers more similar to undifferentiated ESCs,
      suggesting the substrates are restricting differentiation, particularly towards
      the endoderm lineage. Additionally, five days after seeding, we observed
      strikingly different colony morphology, with cells on the SCC substrates growing
      in spherical colonies approximately ten cells thick, while cells on glass were
      growing in flat monolayers. Colonies on the SCC substrates developed a central
      pit, which was never observed in cells cultured on glass, and expressed proteins
      related to epithelialisation. Together, these data demonstrate the potential of
      using topographical cues to control stem cell behaviour in vitro.

PMID- 22370797
TI  - A thermosensitive low molecular weight hydrogel as scaffold for tissue
      engineering.
AB  - Hydrogels that are non-toxic, easy to use, cytocompatible, injectable and
      degradable are valuable biomaterials for tissue engineering and tissue repair.
      However, few compounds currently fulfil these requirements. In this study, we
      describe the biological properties of a new type of thermosensitive hydrogel
      based on low-molecular weight glycosyl-nucleosyl-fluorinated (GNF) compound. This
      gel forms within 25 min by self-assembly of monomers as temperature decreases. It
      degrades slowly in vitro and in vivo. It induces moderate chronic inflammation
      and is progressively invaded by host cells and vessels, suggesting good
      integration to the host environment. Although human adult mesenchymal stem cells
      derived from adipose tissue (ASC) cannot adhere on the gel surface or within a 3D
      gel scaffold, cell aggregates grow and differentiate normally when entrapped in
      the GNF-based gel. Moreover, this hydrogel stimulates osteoblast differentiation
      of ASC in the absence of osteogenic factors. When implanted in mice, gel
      entrapped cell aggregates survive for several weeks in contrast with gel-free
      spheroids. They are maintained in their original site of implantation where they
      interact with the host tissue and adhere on the extracellular matrix. They can
      differentiate in situ into alkaline phosphatase positive osteoblasts, which
      deposit a calcium phosphate-rich matrix. When injected into subcutaneous sites,
      gel-encapsulated cells show similar biological properties as implanted gel-cells
      complexes. These data point GNF-based gels as a novel class of hydrogels with
      original properties, in particular osteogenic potential, susceptible of providing
      new therapeutic solutions especially for bone tissue engineering applications.

PMID- 22370798
TI  - [New therapy approaches in arthritis urica].

PMID- 22370799
TI  - [Off-label therapy in rheumatology].

PMID- 22370800
TI  - [Off-label therapy from the perspective of the medical insurance service].
AB  - The assessment of off-label medications is one of the most common reasons for
      assessment of drugs for individual patients in the German medical services.
      Tension is not uncommon because of great expectations of patients and doctors on
      the one hand and the requirements of the law on the other. They often do not
      match. Even if there is a medically justified off-label use the road to drug
      approval is principally via the authorities with tested efficacy and safety in
      order not to deprive the patient of the protection of the Pharmaceuticals Act.
      The jurisdiction has approved criteria for reimbursement by the statutory health
      insurance only in clearly defined exception and one requirement is that there are
      no alternative forms of treatment. For serious diseases this is based on the
      evidence of drug approval; however, for immediately life-threatening situations a
      very low evidence level is sufficient.

PMID- 22370802
TI  - [Orphan diseases in rheumatology. Exemplified by polyarteritis nodosa].
AB  - The term orphan disease is used for those diseases which are diagnosed in less
      than 5 out of 10,000 persons. An example of an orphan disease in rheumatology is
      panarteritis nodosa (PAN), the clinical manifestation of which ranges from mild
      forms to life-threatening situations. The scientific publications on the
      diagnosis and therapy of PAN are usually limited to casuistics and small case
      studies. Treatment of this disease is usually carried out analogue to other forms
      of vasculitis but the therapeutics used are not formally approved for PAN. With
      this in mind it is much more realistic to treat such patients in specialized
      centers or at least to allow an evidence-based medical treatment in, for example
      network associations, using the targeted documentation of patients.

PMID- 22370801
TI  - [Off-label therapy: current problems from the perspective of the Pharmaceutical
      Commission of the German Medical Profession].
AB  - The off-label use of approved pharmaceuticals outside the authorized status is
      implemented in pharmacotherapy of many diseases, especially for rare diseases and
      in cases of therapy resistance. The German regulations are presented and analyzed
      and the relative literature is discussed.

PMID- 22370803
TI  - [Off-label therapy of rheumatoid arthritis and spondyloarthritis].
AB  - For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a
      large number of approved medications are available. Nevertheless, in Germany even
      for these diseases several off-label risks exist for the rheumatologist
      prescribing antirheumatic drugs which have recently led to a series of recourses
      or threats of recourse. In RA as well as SpA first of all biologicals are the
      target of recourse imposed mainly by health insurances. In RA monotherapy (when
      labeled only in combination with methotrexate), combination with leflunomide
      (instead of methotrexate) and dose deviations are the most important causes. In
      SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing
      spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe
      peripheral spondyloarthritis including enthesitis which does not exactly meet the
      diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling
      the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In
      these cases, however, based on successful randomized controlled trials and
      changed diagnostic criteria a label extension is expected in the near future.
      Until then it seems suitable to apply for permission for this treatment from
      insurers in each case.

PMID- 22370804
TI  - [The etiology and management of gout].
AB  - Gout is an inflammatory arthritis caused by monosodium urate (MSU) crystal
      deposits in and around the joint. The formation of urinary calculi can also occur
      in gout, but are less common than arthritis. Gout usually presents with recurrent
      episodes of joint inflammation, which over time lead to tophus formation and
      joint destruction. In the last decade, significant advances have been made
      regarding not only the epidemiology and genetics of gout and hyperuricemia but
      also the mechanisms of inflammation and treatment of gout. In addition, knowledge
      concerning the key role of interleukin 1 (IL-1) has provided new therapeutic
      perspectives. However, the current management of gout is often suboptimal, with
      many Patienten either not receiving adequate treatment or being unable to
      tolerate existing treatments. New therapeutic agents provide interesting new
      options for Patienten with difficult-to-treat gouty arthritis.The English full
      text version of this is available at SpringerLink (under "Supplemental").

PMID- 22370805
TI  - [Osteoimmunology - IMMUNOBONE - Understanding the interaction between bone and
      immune system].
AB  - The special program "Osteoimmunology" under the leadership of the Universities of
      Erlangen, Jena, Giebetaen and Munster, is investigating in 27 projects
      clarification approaches on the causes of inflammatory rheumatic diseases, such
      as rheumatoid arthritis and ankylosing spondylitis with the aim of developing new
      forms of treatment. The molecular mechanisms involved in bone damage and the
      interaction between the immune system and bone and cartilage are topics of
      research.

PMID- 22370806
TI  - [Practical problems by implementation of vaccination recommendations].
AB  - Patients with inflammatory rheumatic diseases are known to have an increased risk
      of infections due to the rheumatic disease itself and due to therapy with
      immunosuppressive agents. The most important procedure to prevent infections is
      vaccinations, which are usually well-tolerated. The German National Commission
      for Immunization ( STIKO) has published recommendations for patients with an
      immunodeficiency. The German Society of Rheumatology (DGRh) has generally
      implemented these recommendations for patients with chronic inflammatory
      rheumatic diseases. The immunization status of patients with rheumatic diseases
      is of increasing importance in routine patient care because some of the recently
      approved drugs may influence the strength of the immune response to vaccination.
      However, there is almost no information about the current immunization status and
      the willingness of patients with rheumatic diseases to undergo vaccination
      procedures in Germany. There are also no epidemiologic data on the implementation
      of recommendations for immunization at the level of general practitioners. Here
      we present the results of a prospective study on the efficacy of standardized
      recommendations for immunization given to different patient groups with rheumatic
      diseases treated in a hospital specialized in rheumatology.

PMID- 22370809
TI  - Intraoperative DTI and brain mapping for surgery of neoplasm of the motor cortex
      and the corticospinal tract: our protocol and series in BrainSUITE.
AB  - We report our preliminary series of patients treated for lesions involving the
      motor cortex and the corticospinal tract in BrainSuite, with intraoperative MRI,
      tractography and "neuronavigated" electrophysiological cortical and subcortical
      mapping. An exact localization of the cortical and subcortical functional areas
      is mandatory for executing surgery of intra-parenchymal neoplasm involving the
      motor cortex and the corticospinal tract. Nowadays modern technology offers a
      variety of tools to reduce as much as possible postoperative deficits during
      surgery of cerebral eloquent areas. From December 2008 and June 2010, 18 patients
      underwent functional surgery, for neoplasm involving the motor cortex and/or the
      subcortical pathway, in BrainSuite. Our preliminary series include 14 gliomas and
      4 metastases; Table 1 summarizes all of the data. We included in this series
      patients with complete removal of lesions of eloquent areas with an average
      distance from the corticospinal tract of 4 mm. Six neoplasms were considered in
      contact and/or involving the motor cortex, while in 18 cases (100%) the tumour
      involved eloquent areas concerning the corticospinal tract. All of the patients
      underwent complete removal of the lesion as subsequently demonstrated by
      intraoperative postsurgical MRI. Our series highlights the good integration and
      the high compatibility between BrainSUITE with 1.5 T intraoperative magnetic
      field and neurophysiological monitoring. We strongly believe that intraoperative
      MRI with DTI allows us to treat complex surgery tumours that without its auxilium
      we would not be able to deal with.

PMID- 22370810
TI  - The predictive value of serum myeloperoxidase for vasospasm in patients with
      aneurysmal subarachnoid hemorrhage.
AB  - Vasospasm is a major contributor to morbidity and mortality in aneurysmal
      subarachnoid hemorrhage (SAH), with inflammation playing a key role in its
      pathophysiology. Myeloperoxidase (MPO), an inflammatory marker, was examined as a
      potential marker of vasospasm in patients with SAH. Daily serum samples from
      patients with aneurysmal SAH were assayed for MPO, and transcranial Doppler
      (TCDs) and neurological exams were assessed to determine vasospasm. Suspected
      vasospasm was confirmed by angiography. Peak MPO levels were then compared with
      timing of onset of vasospasm, based on clinical exams, TCDs and cerebral
      angiography. Patients with vasospasm had a mean MPO level of 115.5 ng/ml,
      compared to 59.4 ng/ml in those without vasospasm, 42.0 ng/ml in those with
      unruptured aneurysms, and 4.3 ng/ml in normal controls. In patients who
      experienced vasospasm, MPO was elevated above the threshold on the day of, or at
      any point prior to, vasospasm in 10 of 15 events (66.7%), and on the day of, or
      within 2 days prior to, vasospasm in 8 of 15 events (53.3%). Elevated serum MPO
      correlates with clinically evident vasospasm following aneurysmal SAH. The
      potential utility of MPO as a marker of vasospasm is discussed.

PMID- 22370813
TI  - Peptidoglycan as Nod1 ligand; fragment structures in the environment, chemical
      synthesis, and their innate immunostimulation.
AB  - Covering: up to 2011. This review focuses on the recent revealing of the
      immunostimulatory bacterial cell wall peptidoglycan (PGN) fragments as Nod1
      ligands, especially a newly developed chemical synthesis of the partial
      structures, fragment structures in the environment and bacterial supernatant, and
      the immunostimulatory activities of the Nod1 ligands.

PMID- 22370814
TI  - Factor VIIa binding to endothelial cell protein C receptor: differences between
      mouse and human systems.
AB  - Recent  in vitro  studies have shown that the zymogen and activated form of
      factor (F)VII bind to endothelial cell protein C receptor (EPCR). At present,
      there is no evidence that FVIIa binds to EPCR on vascular endothelium  in vivo 
      in the presence of circulating protein C, a primary ligand for EPCR. The present
      study was carried out to investigate the interaction of murine and human ligands
      with murine EPCR both  in vivo  and  in vitro . Measurement of endogenous plasma
      levels of FVII in wild-type, EPCR-deficient and EPCR-over expressing mice showed
      slightly lower levels of FVII in EPCR-over expressing mice. However, infusion of
      high concentrations of competing ligands, either human APCi or FVIIai, to EPCR
      over expressing mice failed to increase plasma levels of mouse FVII whereas they
      increased the plasma levels of protein C by two- to three-fold. Examining the
      association of exogenously administered mouse FVIIa or human FVIIa by
      immunohistochemistry revealed that human, but not murine FVIIa, binds to the
      murine endothelium in an EPCR-dependent manner.  In vitro  binding studies
      performed using surface plasmon resonance and endothelial cells revealed that
      murine FVIIa binds murine EPCR negligibly. Human FVIIa binding to EPCR,
      particularly to mouse EPCR, is markedly enhanced by availability of Mg2+ ions. In
      summary, our data show that murine FVIIa binds poorly to murine EPCR, whereas
      human FVIIa binds efficiently to both murine and human EPCR. Our data suggest
      that one should consider the use of human FVIIa in mouse models to investigate
      the significance of FVIIa and EPCR interaction.

PMID- 22370815
TI  - Anomalous origin of the left coronary artery from the noncoronary cusp: not a
      benign lesion.
AB  - This case report describes two patients with a very rare condition who presented
      with pathologic symptoms. Anomalous origin of the left coronary artery from the
      noncoronary cusp has been described as a "benign" lesion by some authors in the
      past, although rare cases of morbidity/mortality are described in the literature.
      Both reported patients underwent surgical repair for the lesion and at this
      writing are asymptomatic at follow-up evaluation. These two patients presenting
      with pathologic symptoms and undergoing surgery afford novel descriptions. The
      authors believe these descriptions add to our knowledge of this rare disorder.

PMID- 22370816
TI  - Changes in the serum level of hepatitis B virus (HBV) surface antigen over the
      natural course of HBV infection.
AB  - BACKGROUND: Despite its status as a potential biomarker of hepatitis B virus
      (HBV) response to interferon treatment, the changes in hepatitis B surface
      antigen (HBsAg) levels over the natural course of HBV carriers have not been
      analyzed sufficiently. METHODS: A total of 101 HBV carriers were followed
      prospectively from 1999 to 2009. HBsAg level was measured yearly during the
      followed period. RESULTS: HBsAg levels at baseline ranged from -1.4 to 5.32 log
      IU/ml, with a median value of 3.2 log IU/ml. Lower HBsAg levels were
      significantly associated with higher age and lower HBV replication status. The
      rate of change of HBsAg levels showed two peaks, with a cut-off value of -0.4 log
      IU/year. Based on this, patients were tentatively classified into rapid decrease
      (rate of change <-0.4 log IU/year) and non-rapid decrease groups. All baseline
      levels of HBsAg, HB core-related Ag, and HBV DNA were lower in the rapid decrease
      group than in the non-rapid decrease group. Patients with persistently positive
      HBeAg were all classified into the non-rapid decrease group. In patients with
      persistently negative HBeAg, HBV DNA levels were significantly (P = 0.028) lower
      in the rapid decrease group than in the non-rapid decrease group. CONCLUSIONS:
      Lower baseline HBsAg levels were significantly associated with older age and
      lower viral activity. Both a loss of HBeAg detection as well as inactive
      replication of HBV are suggested to be fundamental factors contributing to a
      rapid decrease in HBsAg over the natural course of HBV infection.

PMID- 22370817
TI  - Determinants of the clinical outcome of patients with severe acute exacerbation
      of chronic hepatitis B virus infection.
AB  - BACKGROUND: Severe acute exacerbation of chronic hepatitis B can sometimes occur
      and lead to hepatic failure and death. The objective of this study was to
      elucidate the predictors of progression to hepatic decompensation during severe
      acute exacerbation. METHODS: We prospectively analyzed 37 consecutive patients
      with acute exacerbation of chronic hepatitis B (accompanied by jaundice and
      coagulopathy) for clinical outcome and factors that influenced the development of
      severe acute exacerbation, including viral kinetics. RESULTS: Fourteen (37.8%)
      patients progressed to severe acute exacerbation (accompanied by encephalopathy).
      Multivariate analysis identified serum bilirubin (>5 mg/dl, P = 0.002) as a
      significant determinant of progression to hepatic failure and prothrombin
      activity (<45%, P = 0.028) and as a determinant of liver-related death. The
      hepatitis B virus (HBV) DNA level before therapy was measured in 25 patients. HBV
      DNA levels increased or did not change from before commencement of treatment in
      all 11 patients who progressed to severe acute exacerbation. On the other hand,
      HBV DNA levels did not change or increased in 8 of 14 patients (57%) with acute
      exacerbation (P = 0.02). CONCLUSIONS: Serum bilirubin and prothrombin activities
      were significant predictors of clinical outcome in patients with severe acute
      exacerbation of chronic hepatitis B. Viral kinetics until commencement of therapy
      can predict the severity of acute exacerbation of chronic hepatitis B.

PMID- 22370819
TI  - The new tropical medicine.

PMID- 22370818
TI  - H1N1 as a causative agent in febrile neutropenia of an acute myeloid leukaemia
      (AML) patient.

PMID- 22370820
TI  - S100, CD68, and MHC class II molecule expression in cervical high- and low-grade
      HPV-induced lesions.
AB  - INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant
      processes in the cervical epithelium, with 99% of cases attributed to oncogenic
      HPV infection. This study aimed to detect S100, CD68, and major
      histocompatibility complex class II (MHC-II) molecules in cervical uterine
      epithelial samples in patients with high- and low-grade lesions induced by HPV.
      METHODS: Fifty-eight samples from patients who were confirmed positive or
      negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of
      cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were
      negative for intraepithelial lesion or malignancy were subjected to
      immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha
      chain). RESULTS: The presence of MHC-II predominated in samples exhibiting
      histopathological alterations (p < 0.05). S100 detection was more numerous in
      carcinoma samples (CIN III) (75%). Presence of this protein correlated
      significantly (p < 0.05) with histopathological findings and viral load.
      CONCLUSIONS: A small expression of CD68 was observed, which may be explained by
      the observation in our study having been made on random microscopic fields and
      not on specific areas. The findings, such as the presence of S100 protein and MHC
      II expression in samples with histological alterations, could suggest that the
      immune system fails to control HPV replication at the early stages of infection.
      Further studies with larger prospective data are necessary to confirm this
      result.

PMID- 22370821
TI  - Molecular characterization of the hepatitis B virus in autochthonous and
      endogenous populations in the Western Brazilian Amazon.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is a serious public health issue
      worldwide. Hepatitis B virus is classified into eight genotypes, varying from A
      to H, with distinct geographical distributions. In Brazil, the most frequent
      genotypes are A, D, and F. METHODS: This study aimed to characterize the HBV
      genotypes in cases of hepatitis B virus and hepatitis D virus (HDV) co-infections
      in an endemic area in the Western Brazilian Amazon. We analyzed 86 serum samples
      reactive for HBsAg from indigenous and non-indigenous populations obtained from
      previous serological surveys. RESULTS: Of the 86 reactive serum samples, 39 were
      found to be HBV-DNA-positive by semi-nested PCR. The genotypes were established
      by sequencing the amplified S gene region. We obtained 20 sequences classified
      into three genotypes: A, D, and F. Genotype A was the most frequent (60%),
      followed by D (35%) and F (5%). CONCLUSIONS: The distribution of the HBV
      genotypes reflected the pattern of historical occupation of the region.

PMID- 22370822
TI  - Prevalence of hepatitis B virus infection and carriage after nineteen years of
      vaccination program in the Western Brazilian Amazon.
AB  - INTRODUCTION: Reductions in the prevalence of hepatitis B virus (HBV) infection
      and carriage, decreases in liver cancer incidence, and changes in patterns of
      liver dysfunctions are described after hepatitis B vaccination. METHODS: We
      conducted a population-based seroprevalence study aimed at estimating the HBV
      prevalence and risk of infection in the rural area of Labrea following nineteen
      years of HBV vaccination. RESULTS: Half of the subjects showed total anti-HBc of
      52.1% (95% CI 49.6-54.7). The HBsAg prevalence was 6.2% (95% CI 5.1-7.6).
      Multivariate analysis showed an inverse association between HBV infection and
      vaccination (OR 0.62; 95% CI 0.44-0.87). HBsAg remained independently associated
      with past hepatitis (OR 2.44; 95% CI 1.52-3.89) and inversely to vaccination (OR
      0.43; 95% CI 0.27-0.69). The prevalence of HBeAg among HBsAg-positive individuals
      was 20.4% (95% CI 12.8-30.1), with the positive subjects having a median age of
      11 years (1-46) p=0.0003. CONCLUSIONS: We demonstrate that HBV infection is still
      an important public health issue and that HBV vaccination could have had better
      impact on HBV epidemiology. If we extrapolate these findings to other rural areas
      in the Brazilian Amazon, we can predict that the sources of chronic infected
      patients remain a challenge. Future studies are needed regarding clinical
      aspects, molecular epidemiology, surveillance of acute cases, and risk groups.

PMID- 22370823
TI  - Diagnosis of Leishmania (Leishmania) chagasi infection in dogs and the
      relationship with environmental and sanitary aspects in the municipality of
      Palmas, State of Tocantins, Brazil.
AB  - INTRODUCTION: The aim of the present study was to identify the presence of
      Leishmania (Leishmania) chagasi infection in dogs in the City of Palmas,
      Tocantins, Brazil, using the PCR technique to list the hot spots of infected dogs
      in the city and associate their occurrence to significant environmental changes
      at capture sites. METHODS: DNA was extracted from blood of dogs, and the PCR were
      performed with primers RV1/RV2. After screening the population studied, the
      regions of the city that had the highest occurrence of canine infection were
      detected. These sites were visited, and ecological parameters denoting
      anthropogenic disturbance were evaluated. RESULTS: Some important features were
      listed in the regions visited, such as low urbanization, lack of public
      collection of sewage, limited garbage collection, vacant lots with tall
      vegetation, decaying organic matter, and, most importantly, the occurrence of
      stray dogs and poultry in homes. CONCLUSIONS: The methodology for screening the
      population was very efficient, especially in evaluating a large number of
      individuals in a short time, with a high degree of automation. The results
      indicate an association between the observed parameters and the occurrence of
      infection in dogs. The model presented in the city is ideal for studies of
      disease progression and expansion and for the evaluation of control measures
      adopted for canine VL.

PMID- 22370824
TI  - Clinical and laboratory alterations in dogs naturally infected by Leishmania
      chagasi.
AB  - INTRODUCTION: Canine visceral leishmaniasis (CVL) is a zoonotic disease with
      different clinical manifestations. Parasitism often occurs in bone marrow, but
      changes have been observed in peripheral blood and serum biochemical parameters.
      The aim of this study was to evaluate the hematological and biochemical
      parameters in dogs naturally infected by Leishmania chagasi. METHODS: Eighty-five
      adult dogs of both sexes and various weights and ages from the Zoonosis Control
      Center of Fortaleza (CCZ) were used, selected by immunofluorescence assay (IFA)
      and considered positive with IFA titers greater than 1:40 and by visualizing
      amastigotes of Leishmania chagasi in smears obtained by bone marrow aspiration.
      The dogs (n = 85) were grouped according to clinical signs: negative (CN = 7),
      subclinical (CS = 10), and clinical (CC = 68). Blood samples were collected for
      determination of hematological and biochemical serum values. The experimental
      protocol was approved by the CEUA/UECE. RESULTS: The most frequent clinical signs
      were cachexia (77.9%), keratitis (61.8%), and lymphadenopathy (55.9%), and 86.8%
      of the animals showed more than one clinical sign characteristic of CVL. In CC
      were observed reductions in red blood cells (63%), hematocrit (72%), and
      hemoglobin (62%), as well as leukocytosis (33%), neutropenia (28%),
      thrombocytopenia (50%), uremia (45%), hyperproteinemia (53%, p<0.05),
      hypergammaglobulinemia (62%, p<0.01), and hypoalbuminemia (58%). CONCLUSIONS:
      Animals with the clinical form of the disease demonstrate hematological and
      biochemical changes consistent with anemia, uremia, hyperproteinemia, and
      hyperglobulinemia, which present themselves as strong clinical markers of
      visceral leishmaniasis associated with the signs previously reported.

PMID- 22370825
TI  - Active surveillance of American tegumentary leishmaniasis in endemic areas in
      rural Bolivia.
AB  - INTRODUCTION: American tegumentary leishmaniasis (ATL), including mucocutaneous
      leishmaniasis (MCL) and localized cutaneous leishmaniasis (LCL), is endemic in
      Bolivia. We describe the results of active surveillance of ATL from 2001 to 2006
      and assess demographic data related to ATL epidemiology in the Yungas valleys.
      METHODS: Community-based active ATL surveillance was performed by the
      institutions SERVIR, CARITAS, and the Health Services Department of La Paz, whose
      files were reviewed retrospectively. A cross-sectional survey was carried out to
      assess demographic data in two communities. RESULTS: Two thousand nine hundred
      nine cases of ATL were detected from 2001 to 2006: 2,488 (85.5%) corresponded to
      LCL and 421 (14.5%) to MCL. A reduction in the proportion of mucosal cases was
      observed between 2001 and 2006. The proportion of MCL cases increased with age
      and was higher among males (15.5% versus 12.1%, p=0.018). The rate of positivity
      via direct observation of the parasite in dermal scrapings and in parasite
      cultivation was significantly higher for LCL than for MCL (p<0.001 and p=0.009,
      respectively). The rate of reactivity in the leishmanin skin test was higher in
      the group with mucosal lesions (p=0.012). The cross-sectional survey showed that
      40% of the families had emigrated from the Altiplano. CONCLUSIONS: It is
      necessary to undertake continuous case detection of ATL in the area, where the
      disease presents a high rate of mucosal cases. Increasing incidence seems to be
      associated with immigration and continuous deforestation to expand the crop
      growing areas.

PMID- 22370826
TI  - In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for
      differential diagnosis and evaluation of Chagas disease morbidity.
AB  - INTRODUCTION: The goal was to develop an in-house serological method with high
      specificity and sensitivity for diagnosis and monitoring of Chagas disease
      morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and
      subclasses were tested in successive serum dilutions of patients from Berilo
      municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the
      in-house ELISA was also evaluated in samples from other relevant infectious
      diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral
      leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected
      controls (NI). Further analysis was performed to evaluate the applicability of
      this in-house methodology for monitoring Chagas disease morbidity into three
      groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed
      (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG
      reactivity at serum dilution 1:40 was an excellent approach to Chagas disease
      diagnosis (100% sensitivity and specificity). The analysis of IgG subclasses
      showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum
      dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels
      and the DIG/Mix group presented higher levels of total IgG as compared with the
      IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology
      presents promising applicability in the analysis of anti-T. cruzi IgG reactivity
      for the differential diagnosis and evaluation of Chagas disease morbidity.

PMID- 22370827
TI  - Production of cytokine and chemokines by human mononuclear cells and whole blood
      cells after infection with Trypanosoma cruzi.
AB  - INTRODUCTION: The innate immune response is the first mechanism of protection
      against Trypanosoma cruzi, and the interaction of inflammatory cells with
      parasite molecules may activate this response and modulate the adaptive immune
      system. This study aimed to analyze the levels of cytokines and chemokines
      synthesized by the whole blood cells (WBC) and peripheral blood mononuclear cells
      (PBMC) of individuals seronegative for Chagas disease after interaction with live
      T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-alpha, TGF-beta, CCL-5, CCL
      2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess
      method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC,
      even after incubation with live trypomastigotes. Production of TNF-alpha by both
      PBMC and WBC was significantly higher after stimulation with trypomastigotes.
      Only PBMC produced significantly higher levels of IL-12 after parasite
      stimulation. Stimulation of cultures with trypomastigotes induced an increase of
      CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after
      the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T.
      cruzi may induce the production of cytokines and chemokines by cells of the
      innate immune system through the activation of specific receptors not evaluated
      in this experiment. The ability to induce IL-12 and TNF-alpha contributes to
      shift the adaptive response towards a Th1 profile.

PMID- 22370828
TI  - Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2
      strain.
AB  - INTRODUCTION: To evaluate the efficacy of vitamin C in reducing the consequences
      generated by the production of free radicals in the acute and chronic phases of
      Chagas disease, two different doses of ascorbic acid were administered orally to
      60 mice infected by Trypanosoma cruzi QM2 strain. METHODS: The animals were
      divided into six groups: G1, G2, and G3 for the acute phase study, and G'1, G'2,
      and G'3 for the chronic stage. The groups G1 and G'1 received 8.6 x 10-4 mg/g of
      vitamin C daily, whereas G2 and G'2 received 7.14 x 10-3 mg/g daily. The other
      groups, G3 and G'3, were considered placebos and received 10 uL of mineral water.
      RESULTS: The study of the acute phase showed statistically significant
      differences between G1 and the other groups at various count days of the
      parasitemia evolution. The multiplying parasite was slower in G1 until the 11th
      day, but on the 22nd day it had greater parasitemia than in G2 and G3, and from
      the 36th day on, parasitemia stabilized at higher levels. However, when the
      histopathology of acute and chronic phases is considered, one does not note
      significant differences. CONCLUSIONS: The administration of two different doses
      of vitamin C was not able to protect mice and to contain the oxidative stress
      caused by free radicals formed by the metabolism of oxygen (reactive oxygen
      species) and nitrogen (reactive nitrogen species).

PMID- 22370829
TI  - Profile of pregnant women and children treated at a reference center for
      congenital toxoplasmosis in the northern state of Minas Gerais, Brazil.
AB  - INTRODUCTION: To describe the clinical and epidemiological profile of pregnant
      women and children treated at a reference outpatient clinic for congenital
      toxoplasmosis. METHODS: Pregnant women potentially exposed to Toxoplasma gondii
      were observed. Diagnoses were made using serologic tests compatible with acute
      toxoplasmosis. Children presenting with: Toxoplasma-specific antibodies (IgM or
      IgA or ascending IgG titers higher than maternal titers in the first 3 months of
      life) coupled with toxoplasmosis symptoms; intracranial calcifications (by
      transfontanelar ultrasound or cephalic segment tomography); or retinochoroiditis
      (by fundoscopy examination) in the first 8 months of life were also included in
      the study. RESULTS: Fifty-eight mother-child pairs were observed (mean age of the
      mothers was 22.1 years). Most patients lived in urban areas (86.2%) and had
      attended less than 8 years of school (51.7%). Diagnosis was made after birth in
      19 (32.8%) children. Thirty-four (58.6%) women received some type of treatment
      during pregnancy. Most (72.4%) of the children did not present with clinical
      alterations at birth. The main findings were ophthalmological: 20 (34.5%)
      children with retinochoroiditis, 17 (29.3%) with strabismus, and 7 (12.1%) with
      nystagmus. Of the children with retinochoroiditis, 9 presented with subnormal
      vision. Ten (32.3%) out of 31 children presented with intracranial calcifications
      by cephalic segment congenital toxoplasmosis, and 9 (42.9%) children presented
      with delayed psychomotor development. CONCLUSIONS: Our results highlight a
      critical situation. Protocols for follow-up of pregnant women and their children
      must be created to improve medical care and minimize sequelae.

PMID- 22370830
TI  - Synanthropic triatomines (Hemiptera, Reduviidae) in the state of Pernambuco,
      Brazil: geographical distribution and natural Trypanosoma infection rates between
      2006 and 2007.
AB  - INTRODUCTION: The present study shows a descriptive analysis of triatomine
      occurrence and its natural Trypanosoma infection rates in the state of
      Pernambuco, Brazil, between 2006 and 2007. METHODS: Entomological data for the
      species, such as specimens captured in both intra and peridomiciles and natural
      infection index, were obtained via domiciliary capture in 147 municipalities from
      11 Regional Managements of Health. The database was obtained from a sample of
      insects (100% infected and 20% non-infected) sent to the Central Laboratory of
      Pernambuco. RESULTS: A total of 18,029 triatomines were analyzed from 138
      municipalities of the state. Triatoma pseudomaculata (35%), Triatoma brasiliensis
      (34%), and Panstrongylus lutzi (25%) were the most captured species. These
      species also showed a widespread geographical distribution in the state.
      Panstrongylus megistus, Triatoma petrocchiae, Triatoma melanocephala, Triatoma
      sordida, Rhodnius nasutus, Rhodnius neglectus, and Triatoma infestans showed more
      limited geographical distribution and lower relative abundance. The
      parasitological research showed that 8.8% of the triatomines were naturally
      infected with flagellates morphologically similar to Trypanosoma cruzi and 91.3%
      of them were captured inside houses in 113 municipalities. P. lutzi showed the
      highest rates of natural infection. CONCLUSIONS: After the control of T.
      infestans, synanthropic species, such as T. brasiliensis, T. pseudomaculata, and
      P. lutzi, maintain the risk of T. cruzi transmission to humans in the state of
      Pernambuco. These species are widely distributed, and infected specimens have
      been found inside houses. Thus, an enhanced surveillance and vector control of
      Chagas disease is recommended in Pernambuco.

PMID- 22370831
TI  - Phlebotomine sandflies (Diptera: Psychodidae) in Sao Vicente Ferrer, a sympatric
      area to cutaneous and visceral leishmaniasis in the state of Pernambuco, Brazil.
AB  - INTRODUCTION: In the last decades, a considerable geographic expansion of the
      leishmaniases in all regions of Brazil has been observed. The present study was
      carried out to identify the composition of the phlebotomine sandfly fauna and
      verify the seasonal variation of the main species after environmental changes
      occurred in Sao Vicente Ferrer Municipality, State of Pernambuco, Brazil.
      METHODS: Captures were carried out during four consecutive nights of each month
      using Centers for Disease Control and Prevention light traps from September 2009
      to September 2010. The correlation between the number of phlebotomine sandflies
      captured and climatic factors (temperature and rainfall) was evaluated. RESULTS:
      A total of 13,872 specimens belonging to 20 species were captured, of which,
      6,247 (45%) were females, and 7,625 (55%) were males. Lutzomyia migonei was the
      most abundant species with 9,964 (71.8%) specimens, being predominant in the
      intradomicile and peridomicile areas with 108 (86.4%) and 9,746 (97%),
      respectively. In the forest remnants, Lutzomyia complexa 2,395 (65%) and
      Lutzomyia sordellii 770 (20.8%) predominated. The correlation analysis between
      the total number of sandflies captured and climatic factors did not show a
      significant influence on population density. CONCLUSIONS: The high abundance of
      Lutzomyia migonei and Lutzomyia complexa indicates the possibility of new cases
      of cutaneous leishmaniasis (CL).

PMID- 22370832
TI  - Occurrence of synanthropic triatomines (Hemiptera: Reduviidae) in the Federal
      District of Brazil.
AB  - INTRODUCTION: Entomological surveillance of Chagas disease in the Federal
      District of Brazil (DF), has recorded the following triatomine species:
      Panstrongylus megistus, P. geniculatus, P. diasi, Rhodnius neglectus, Triatoma
      pseudomaculata, and T. sordida. We aimed to analyze the spatial and temporal
      occurrence of triatomine species collected in DF, and their indices of natural
      infection with trypanosomes. METHODS: The Health State Secretariat of DF recorded
      triatomines between 2002 and 2010 in 20 administrative regions. This
      retrospective analysis considered the number of adults and nymphs of each species
      collected and infected in both intradomicile and peridomicile. RESULTS: A total
      of 754 triatomines were collected in 252 reported domiciles. Panstrongylus
      megistus was the most frequent species (65%), followed by T. pseudomaculata
      (14%). Of the 309 examined insects, only 3 (1%) specimens of P. megistus were
      infected with flagellates morphologically similar to Trypanosoma cruzi. The
      spatial occurrence indicated a higher diversity of triatomines and frequency of
      T. sordida in rural areas. Moreover, there was a predominance of P. megistus in
      urban areas. The number of records of P. megistus in the rainy season was two
      times higher than that during the dry season. The largest number of triatomines
      was collected in November. CONCLUSIONS: The presence of P. megistus specimens
      infected with trypanosomes in domiciles, shows the potential risk of human
      infection in DF. Thus, it is essential to continue entomological surveillance,
      intensifying it in the rainy season and in regions of greater occurrence.

PMID- 22370833
TI  - Sandfly frequency in a clean and well-organized rural environment in the state of
      Parana, Brazil.
AB  - INTRODUCTION: Sandflies caught in Santa Juliana Farm in Sarandi, State of Parana,
      Brazil, were assessed in terms of their fauna, seasonality, and frequency in the
      homes and in shelters of domestic animals around the homes, as well as in the
      nearby forest. METHODS: In Santa Juliana Farm, there are no records of cases of
      ACL, differing from other relatively clean and organized areas where surveys of
      sandflies have been conducted in Parana. Samples were collected with Falcao light
      traps, fortnightly from 22:00 to 02:00 hours, from November 2007 to November
      2008. RESULTS: A total of 4,506 sandflies were captured, representing 13 species,
      predominantly Nyssomyia whitmani (71.8%). More sandflies were collected in the
      forest (52.6%) than outside the forest (residences and pigsty) (47.4%). However,
      Ny. whitmani was collected in greater numbers outside (38.3%) than inside the
      forest (33.5%). Most sandflies were collected in the warmer months and during
      periods with regular rainfall. CONCLUSIONS: The results suggest that cleaning and
      organization around the houses could reduce sandfly population in peridomicile.
      Constructing shelters for animal at a distance of approximately 100m from
      domiciles is recommended to prevent the invasion of sandflies, as this farm has
      an area of preserved forest, with wild animals and sandflies present to maintain
      the enzootic cycle of Leishmania.

PMID- 22370834
TI  - Electromyography function, disability degree, and pain in leprosy patients
      undergoing neural mobilization treatment.
AB  - INTRODUCTION: This study aimed to evaluate the effect of the neural mobilization
      technique on electromyography function, disability degree, and pain in patients
      with leprosy. METHODS: A sample of 56 individuals with leprosy was randomized
      into an experimental group, composed of 29 individuals undergoing treatment with
      neural mobilization, and a control group of 27 individuals who underwent
      conventional treatment. In both groups, the lesions in the lower limbs were
      treated. In the treatment with neural mobilization, the procedure used was
      mobilization of the lumbosacral roots and sciatic nerve biased to the peroneal
      nerve that innervates the anterior tibial muscle, which was evaluated in the
      electromyography. RESULTS: Analysis of the electromyography function showed a
      significant increase (p<0.05) in the experimental group in both the right
      (Delta%=22.1, p=0.013) and the left anterior tibial muscles (Delta%=27.7,
      p=0.009), compared with the control group pre- and post-test. Analysis of the
      strength both in the movement of horizontal extension (Delta%right=11.7,
      p=0.003/Delta%left=27.4, p=0.002) and in the movement of back flexion
      (Delta%right=31.1; p=0.000/Delta%left=34.7, p=0.000) showed a significant
      increase (p<0.05) in both the right and the left segments when comparing the
      experimental group pre- and post-test. The experimental group showed a
      significant reduction (p=0.000) in pain perception and disability degree when the
      pre- and post-test were compared and when compared with the control group in the
      post-test. CONCLUSIONS: Leprosy patients undergoing the technique of neural
      mobilization had an improvement in electromyography function and muscle strength,
      reducing disability degree and pain.

PMID- 22370835
TI  - Epidemiological, clinical, and operational aspects of leprosy patients assisted
      at a referral service in the state of Maranhao, Brazil.
AB  - INTRODUCTION: Leprosy is an infectious disease caused by Mycobacterium leprae.
      The aim of this study was to describe the epidemiological, clinical, and
      operational aspects of leprosy carriers. METHODS: A cross-sectional study leprosy
      patients assisted in Sao Luis, MA, was performed. RESULTS: Of the 85 cases
      analyzed, 51.7% were male participants, and 60% were brown. Concerning the age,
      54.8% of women were between 35 and 49 years, and 57.6% of men were between 20 and
      34 years. Lepromatous leprosy was found in 42.3% of cases, and the multibacillary
      form was found in 72.9%. The skin smear was positive in 42.3%. The occurrence of
      reaction was found in 43.5% of cases, and 83.5% had no Bacillus Calmette-Guerin
      scar. Leprosy in the family was reported by 44.7% of the patients. Most of the
      individuals (96.4%) lived in houses made of brick with more than three rooms
      (72.6%) and two persons per room (65.1%). Concerning the level of education,
      41.4% of women and 34.1% of men had more than one to three years of education.
      The most evaluated age group in the beginning of the treatment was that of 35 to
      49 years with a Grade 0 incapability (64.5%), and that in the end was the age
      group of 20 to 34 (29.9%) with Grade 0, 30.7% Grade 1, and 11.5% Grade 2.
      CONCLUSIONS: The frequency of multibacillary forms found in this study and the
      cases in family members point out delayed diagnoses. Thus, early diagnosis and
      appropriate treatment are important in decreasing the outcome of disabilities.

PMID- 22370836
TI  - Drug resistance of Mycobacterium tuberculosis strains in southern Brazil.
AB  - INTRODUCTION: The aim of this work was to evaluate the prevalence of
      Mycobacterium tuberculosis (MT) strains with mutations that could result in
      resistance to the main drugs used in treatment in a region with one of the
      highest numbers of tuberculosis (TB) cases in southern Brazil. METHODS:
      Deoxyribonucleic acid (DNA) from 120 sputum samples from different patients
      suspicious of pulmonary tuberculosis who attended the Municipal Public Laboratory
      for Mycobacterium sp. diagnosis was directly amplified and analyzed by PCR-SSCP.
      The DNA was amplified in known hotspot mutation regions of the genes rpoB, ahpC,
      embB, katG, inhA, and pncA. RESULTS: The percentage of samples positive by
      culture was 9.2% (11/120); 5% (6/120) were positive by bacilloscopy and MT-PCR,
      and DNA fragments of the aforementioned resistance genes could be amplified from
      seven (7) of the eleven (11) samples with positive results, either by culture or
      PCR/bacilloscopy. All presented a SSCP pattern similar to a native, nonresistant
      genotype, with the ATCC strain 25177 as control, except for one sample (0.01%),
      which presented a SSCP profile demonstrating mutation at the embB gene.
      CONCLUSIONS: These results are consistent with the empirical observations by
      physicians treating TB patients in our region of a low occurrence of cases that
      are refractory to conventional treatment schemes, in contrast to other parts of
      the country. Continued surveillance, especially molecular, is essential to detect
      and monitor the outbreak of MT-resistant strains.

PMID- 22370837
TI  - Geographic analysis on the occurrence of human and canine leptospirosis in the
      city of Maringa, state of Parana, Brazil.
AB  - INTRODUCTION: Leptospirosis is a zoonotic disease, the primary hosts of which are
      wild, synanthropic, and household animals. Humans behave as terminal and
      accidental hosts. The prevalence of leptospirosis depends on carrier animals that
      disseminate the agent, on the environmental survival of this agent, and on the
      contact of susceptible individuals. Each serovar has one or more hosts with
      different adaptation levels. The focuses of leptospirosis are infected, sick, and
      asymptomatic animals, which are considered to be sources of environmental
      infection. This study aimed to determine the risk areas for leptospiral infection
      in stray dogs and patients diagnosed with leptospirosis from 2006 to 2008 in
      Maringa, State of Parana, Brazil. METHODS: Three hundred and thirty-five stray
      dogs and 25 patients were studied. Serum from both animals and patients was
      examined by the microscopic serum agglutination test to study anti-leptospiral
      antibodies. To determine the risk areas and the spatial distribution of the
      disease, thematic maps were designed. RESULTS: Forty-one (12.2%) dogs positive
      for one or more leptospire serovars were observed, the most frequent serovars
      being Pyrogenes (43.9%), Canicola (21.9%), and Copennhageni (19.5%). Among the
      humans, 2 (8%) were positive for serovars Pyrogenes and Hardjo Prajitno and for
      Pyrogenes and Cynopteri. CONCLUSIONS: Spatial analysis showed that the risk for
      dogs and humans in the City of Maringa to become infected with leptospires exists
      in both the central and the peripheral areas, a fact that reinforces the
      relevance of this study and of continuous epidemiological and environmental
      surveillance actions to control the disease in animals and in humans.

PMID- 22370838
TI  - Relationship between antibiotic consumption, oropharyngeal colonization, and
      ventilator-associated pneumonia by Staphylococcus aureus in an intensive care
      unit of a Brazilian teaching hospital.
AB  - INTRODUCTION: his study evaluated the consumption of major classes of
      antibiotics, the colonization of the oropharynx of patients on mechanical
      ventilation, and the risk of ventilator-associated pneumonia (VAP) caused by
      Staphylococcus aureus in an intensive care unit for adults. METHODS: A case
      control study was carried out using colonized patients (cases) by oxacillin
      resistant S. aureus (ORSA) and (controls) oxacillin-sensitive S. aureus (OSSA)
      from May 2009 to August 2010. The occurrence of VAP by S. aureus was also
      evaluated in the same period. Antibiotic consumption was expressed as the number
      of defined daily doses (DDD)/1,000 patient-days for glycopeptides, carbapenems,
      and extended-spectrum cephalosporins. RESULTS: Three hundred forty-six (56.1%)
      patients underwent mechanical ventilation with a frequency of oropharyngeal
      colonization of 36.4%, corresponding to 63.5% for ORSA and 36.5% for OSSA. The
      risk of illness for this organism was significant (p<0.05), regardless of whether
      colonization/infection was by ORSA or OSSA. The consumption of antibiotics was
      high, mainly for broad-spectrum cephalosporins (551.26 DDDs/1,000 patient-days).
      The high density of use of glycopeptides (269.56 DDDs/1,000 patient-days) was
      related to colonization by ORSA (Pearson r=0.57/p=0.02). Additionally, age >60
      years, previous antibiotic therapy, and previous use of carbapenems were
      statistically significant by multivariate analysis. CONCLUSIONS: There was a
      significant relationship between the colonization of the oropharyngeal mucosa and
      the risk of VAP by both phenotypes. The use of glycopeptides was related to
      colonization by ORSA.

PMID- 22370839
TI  - The effect of Lactobacillus casei and Bifidobacterium breve on antibiotic
      associated diarrhea treatment: randomized double-blind clinical trial.
AB  - INTRODUCTION: Antibiotic-associated diarrhea (AAD) is an important side effect of
      this specific class of drugs. The objective of this study was to investigate the
      effect of the use of probiotics in the treatment of AAD. METHODS: A group of
      hospitalized patients, who contracted diarrhea during or after 7 days of
      suspension of antimicrobial medication, was blindly randomized to receive a
      standardized diet associated with the use of the probiotics (Lactobacillus casei
      and Bifidobacterium breve) or its corresponding placebo, three times a day.
      RESULTS: Seventy patients were studied. For the experimental (n=35) and control
      (n=35) groups, respectively, the average time of treatment was 5.06+/-2.18 and
      5.49+/-3.17 days (p=0.95), and the average duration of diarrhea, among those who
      were healed, was 4.87+/-2.13 and 4.52+/-2.55 days (p=0.36). Four (11.4%) patients
      who received probiotics and ten (28.6%) who received the placebo were not cured
      (p=0.13), and relapse rates were similar between both groups. Seven patients from
      each group, in addition to diarrhea, presented cases of bloating and/or abdominal
      cramps and/or vomiting (p=1.00). CONCLUSIONS: In this light, it is concluded that
      L. casei associated with B. breve, in the administered dosage and frequency, has
      no effect on the antibiotic-associated diarrhea. Similar studies need to be
      conducted with higher doses of these or other probiotics.

PMID- 22370840
TI  - Prevalence of serum antibodies to hantavirus in a rural population from the
      Southern State of Santa Catarina, Brazil.
AB  - INTRODUCTION: Rodent-borne hantaviruses cause severe human diseases. We completed
      a serological survey of hantavirus infection in rural inhabitants of Turvo
      County, in the southern State of Santa Catarina, Brazil, in which seropositivity
      for hantavirus was correlated to previous disease in the participants. METHODS:
      The levels of IgG antibodies to hantavirus Araraquara in the sera of 257
      individuals were determined using an immunoenzymatic assay. RESULTS: IgG
      antibodies to hantavirus were found in 2.3% of the participants. All seropositive
      participants reported previous disease with symptoms suggestive of hantavirus
      cardiopulmonary syndrome. CONCLUSIONS: Human infections causing unreported
      cardiopulmonary syndrome probably occur in the southern State of Santa Catarina.

PMID- 22370841
TI  - Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) in the region of
      Saquarema: potential area of visceral leishmaniasis transmission in the state of
      Rio de Janeiro, Brazil.
AB  - INTRODUCTION: Lutzomyia longipalpis is the main vector of Leishmania infantum
      chagasi in the Americas. METHODS: Phlebotomine captures were conducted during
      2008 and 2009 in a rural area endemic for cutaneous leishmaniasis located in the
      municipality of Saquarema, Rio de Janeiro. RESULTS: Among other species captured,
      we observed the presence of Lutzomyia longipalpis. CONCLUSIONS: This is the first
      report of the occurrence of Lutzomyia longipalpis in this region, demonstrating
      the potential risk of visceral leishmaniasis transmission in the coastal area of
      the State of Rio de Janeiro. Therefore, active vigilance by all municipalities in
      the area is necessary.

PMID- 22370842
TI  - Incidence of congenital toxoplasmosis in the City of Belem, State of Para,
      Northern Brazil, determined by a neonatal screening program: preliminary results.
AB  - INTRODUCTION: The aim of this study was to determinate the incidence of
      congenital toxoplasmosis among a group of newborns (NBs) from Belem using
      neonatal screening. METHODS: Among the 6,000 newborns referred for investigation
      of genetic and metabolic diseases, 1,000 were selected for screening for
      congenital toxoplasmosis by determining the amount of IgM in the eluates of blood
      collected on filter paper. Positive tests were confirmed using paired serology of
      the NB and his mother. RESULTS: Out of the 1,000 NBs assessed, one had a positive
      screening result that was confirmed by paired serology. CONCLUSIONS: The
      incidence of congenital toxoplasmosis in Belem was 10/10,000 live NBs.

PMID- 22370843
TI  - Fauna of Culicidae in rural areas of Porto Velho and the first record of Mansonia
      (Mansonia) flaveola (Coquillet, 1906), for the state of Rondonia, Brazil.
AB  - INTRODUCTION: Knowledge concerning the fauna of Culicidae in the Brazilian Amazon
      States contributes to current understanding of the bionomics of the insects
      collected and makes it possible to observe changes in the fauna over time.
      METHODS: The Culicidae were captured with a BG-Sentinel(r) trap in extra
      domiciliary area of two rural regions of Porto Velho in June and July of 2007 and
      2008. RESULTS: A total of 10,695 Culicidae was collected, belonging to nine
      genera: Coquillettidia, Culex, Mansonia, Psorophora, Aedes, Aedeomyia, Anopheles,
      Uranotaenia and Wyeomyia. CONCLUSIONS: The presence of Mansonia (Mansonia)
      flaveola was recorded in the State of Rondonia for the first time.

PMID- 22370844
TI  - Chikungunya virus infection: report of the first case diagnosed in Rio de
      Janeiro, Brazil.
AB  - Initially diagnosed in Africa and Asia, the Chikungunya virus has been detected
      in the last three years in the Caribbean, Italy, France, and the United States of
      America. Herein, we report the first case for Rio de Janeiro, Brazil, in 2010.

PMID- 22370845
TI  - Splenectomy in a patient with treatment-resistant visceral leishmaniasis: a case
      report.
AB  - Visceral leishmaniasis (VL), also known as Kala-azar, is a systemic infection
      caused by a protozoan (Leishmania) and, in its classic form, is a serious illness
      associated with malnutrition, anemia, hepatosplenomegaly, infectious processes
      and coagulopathies. The effect of splenectomy in patients with visceral
      leishmaniasis is not well defined; however, it is known that the spleen is the
      largest reservoir of infected cells belonging to the reticulo endothelial system.
      Therefore, the surgical procedure is an option for the debulking of parasites,
      providing a cure for refractory VL and minimizing the complications of
      hypersplenism.

PMID- 22370846
TI  - Severe coinfection of melioidosis and dengue fever in Northeastern Brazil: first
      case report.
AB  - This report focuses on a fatality involving severe dengue fever and melioidosis
      in a 28-year-old truck driver residing in Pacoti in northeastern Brazil. He
      exhibited long-term respiratory symptoms (48 days) and went through a wide
      ranging clinical investigation at three hospitals, after initial clinical
      diagnoses of pneumonia, visceral leishmaniasis, tuberculosis, and fungal sepsis.
      After death, Burkholderia pseudomallei was isolated in a culture of ascitic
      fluid. Dengue virus type 1 was detected by polymerase chain reaction in
      cerebrospinal fluid (CSF); this infection was the cause of death. This
      description reinforces the need to consider melioidosis among the reported
      differential diagnoses of community-acquired infections where both melioidosis
      and dengue fever are endemic.

PMID- 22370847
TI  - Abnormal spontaneous interleukin 8 receptor expression: a brief report of two
      cases.
AB  - Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction
      and activation of granulocytes, NKT cells and T lymphocytes. Patients with
      tuberculosis and latent Mycobacterium tuberculosis infection were assessed for
      the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and
      monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression
      and normal CXCR1 expression were found on lymphocytes in two out of 59
      individuals. Monocytes showed normal ex vivo profiles for both receptors. After
      stimulation with purified protein derivative, the in vitro levels of CXCL8 were
      below the median levels of all patients with prior tuberculosis. Spontaneous
      CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8.

PMID- 22370848
TI  - First occurrence of the human biting midge Leptoconops brasiliensis (Lutz)
      (Diptera: Ceratopogonidae) in the triple border of Brazil, Peru, and Bolivia.

PMID- 22370849
TI  - SARIMA for predicting the cases numbers of dengue.

PMID- 22370850
TI  - Radiological appearance of small bowel in severe strongyloidiasis.

PMID- 22370852
TI  - Effect of clothing weight on body weight.
AB  - BACKGROUND: In clinical settings, it is common to measure weight of clothed
      patients and estimate a correction for the weight of clothing, but we can find no
      papers in the medical literature regarding the variability in clothing weight of
      adults with weather, season and gender. METHODS: Fifty adults (35 women) were
      weighed four times during a 12-month period with and without clothing. Clothing
      weights were determined and regressed against minimum, maximum and average daily
      outdoor temperature. RESULTS: The average clothing weight (+/-s.d.) throughout
      the year was significantly greater in men than in women (1.2+/-0.3 vs 0.8+/-0.3
      kg, P<0.0001). The average within-person minimum and the average within-person
      maximum clothing weights across the year were 0.9+/-0.2 and 1.5+/-0.4 kg for men,
      and 0.5+/-0.2 and 1.1+/-0.4 kg for women, respectively. The within-person s.d. in
      clothing weight was 0.3 kg for both men and women. Over the 55  degrees C range
      in the lowest to the highest outdoor temperatures, the regressions predicted a
      maximal change in clothing weight of only 0.4 kg in women and 0.6 kg in men.
      CONCLUSION: The clothing weight of men is significantly greater than that of
      women, but there is little variability throughout the year. Therefore, a clothing
      adjustment of approximately 0.8 kg for women and 1.2 kg for men is appropriate
      regardless of outdoor temperature.

PMID- 22370854
TI  - Activins in adipogenesis and obesity.
AB  - Activins are secreted proteins members of the transforming growth factor-beta
      family. They are involved in many biological responses including regulation of
      apoptosis, proliferation and differentiation of different cell types. Activins A,
      B and AB are highly expressed in adipose tissue, and in this review we will
      illustrate that activins have a role in several steps of physiological and
      pathological development of adipose tissue. Activin A has been shown to be a
      critical regulator of human adipocyte progenitor proliferation and a potent
      inhibitor of their differentiation. Activin A could also be a mediator of
      fibrosis observed in obese adipose tissue. Activin B/AB is proposed as a new
      adipokine having a role in energy balance and insulin insensitivity associated
      with obesity. Therefore, activin pathway could represent a potential therapeutic
      target both for controlling the size and the phenotype of the adipose precursor
      pool and for obesity-associated metabolic complications.

PMID- 22370855
TI  - Selecting and isolating colonies of human induced pluripotent stem cells
      reprogrammed from adult fibroblasts.
AB  - Herein we present a protocol of reprogramming human adult fibroblasts into human
      induced pluripotent stem cells (hiPSC) using retroviral vectors encoding Oct3/4,
      Sox2, Klf4 and c-myc (OSKM) in the presence of sodium butyrate (1-3). We used
      this method to reprogram late passage (>p10) human adult fibroblasts derived from
      Friedreich's ataxia patient (GM03665, Coriell Repository). The reprogramming
      approach includes highly efficient transduction protocol using repetitive
      centrifugation of fibroblasts in the presence of virus-containing media. The
      reprogrammed hiPSC colonies were identified using live immunostaining for Tra-1
      81, a surface marker of pluripotent cells, separated from non-reprogrammed
      fibroblasts and manually passaged (4,5). These hiPSC were then transferred to
      Matrigel plates and grown in feeder-free conditions, directly from the
      reprogramming plate. Starting from the first passage, hiPSC colonies demonstrate
      characteristic hES-like morphology. Using this protocol more than 70% of selected
      colonies can be successfully expanded and established into cell lines. The
      established hiPSC lines displayed characteristic pluripotency markers including
      surface markers TRA-1-60 and SSEA-4, as well as nuclear markers Oct3/4, Sox2 and
      Nanog.     The protocol presented here has been established and tested using
      adult fibroblasts obtained from Friedreich's ataxia patients and control
      individuals( 6), human newborn fibroblasts, as well as human keratinocytes.

PMID- 22370856
TI  - Low power, non-coherent sensitized photon up-conversion: modelling and
      perspectives.
AB  - In the last few years, non-coherent sensitized photon up-conversion (SUC) in
      multi-component systems has been developed to achieve significantly high quantum
      yields for various chromophore combinations at low excitation powers, spanning
      from the ultraviolet (UV) to near infrared (NIR) spectrum. This promising photon
      energy management technique became indeed suitable for wide applications in
      lighting technology and especially in photovoltaics, being able to recover the
      sub-bandgap photons lost by current devices. A full and general description of
      the SUC photophysics will be presented, with the analysis of the parameter
      affecting the photon conversion quantum yield and the quantities which define the
      optimal working range of any SUC system, namely the threshold and saturation
      excitation intensity. It will be shown how these quantities depend on intrinsic
      photophysical properties of the moieties involved and on the SUC solid host
      matrix. The model proposed represents a powerful tool for evaluation of a newly
      proposed system, and its reliability will be discussed in respect to an optimized
      system with SUC yield of 0.26 +/- 0.02. The results obtained will outline the
      research guidelines which must be pursued to optimize the SUC efficiency for its
      perspective technological applications.

PMID- 22370853
TI  - Liver X receptors and fat cell metabolism.
AB  - Liver X receptors (LXRs) are members of the nuclear receptor family and are
      present in two isoforms, alpha and beta, encoded by two separate genes.
      Originally described in the liver, LXRs have in the last 15 years been implicated
      in central metabolic pathways, including bile acid synthesis, lipid and glucose
      homeostasis. Although the vast majority of studies have been performed in non
      adipose cells/tissues, results in recent years suggest that LXRs may have
      important modulatory roles in adipose tissue and adipocytes. Although several
      authors have published reviews on LXR, there have been no attempts to summarize
      the effects reported specifically in adipose systems. This overview gives a brief
      introduction to LXR and describes the sometimes-contradictory results obtained in
      murine cell systems and in rodent adipose tissue. The so far very limited number
      of studies performed in human adipocytes and adipose tissue are also presented.
      It should be apparent that although LXR may impact on several different pathways
      in metabolism, the clinical role of LXR modulation in adipose tissue is still not
      clear.

PMID- 22370857
TI  - Perfluorooctanoic acid exposure and pregnancy outcome in a highly exposed
      community.
AB  - BACKGROUND: We assessed the association between perfluorooctanoic acid (PFOA) and
      pregnancy outcome in an area with elevated exposure to PFOA from drinking water
      contaminated by chemical plant releases. METHODS: Serum PFOA was measured, and
      reproductive and residential histories were obtained during 2005-2006. We
      estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies
      occurring between 1990 and 2006, based on historical information on PFOA
      releases, environmental distribution, pharmacokinetic modeling, and residential
      histories. We assessed the association between PFOA and the odds of miscarriage,
      stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects,
      controlling for calendar time, age, parity, education, and smoking. PFOA exposure
      was evaluated as a continuous measure (with and without log transformation) and
      in quintiles, combining the lowest 2 quintiles (< 6.8 ng/mL) as the referent.
      RESULTS: Measures of association between PFOA and miscarriage, preterm birth,
      term low birthweight, and birth defects were close to the null. Odds of
      stillbirth were elevated in the fourth quintile only. For preeclampsia, the odds
      ratio was 1.13 (95% confidence interval = 1.00-1.28) for an interquartile shift
      in log-transformed PFOA, and the odds ratios were 1.1-1.2 across the upper 3
      quintiles of exposure. CONCLUSIONS: In this large, population-based study in a
      region with markedly elevated PFOA exposure, we found no associations between
      estimated serum PFOA levels and adverse pregnancy outcomes other than possibly
      preeclampsia. Conclusions are tempered by inherent limitations in exposure
      reconstruction and self-reported pregnancy outcome information.

PMID- 22370859
TI  - From small acorns . . . the new Cat Friendly Clinic/Cat Friendly Practice
      programmes.

PMID- 22370858
TI  - Pharmacogenetics of asthma controller treatment.
AB  - The interpatient variability in response to asthma controllers is significant and
      associates with pharmacogenomic variability. The goal of the present study was to
      identify novel variants that associate with response to common asthma
      controllers: fluticasone, combination of fluticasone + salmeterol and montelukast
      with single nucleotide polymorphisms (SNPs) in beta2-adrenergic receptor,
      corticosteroid and leukotriene pathway candidate genes. Participants in a large
      clinical trial of step-down strategies volunteered for this pharmacogenetic
      study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian
      participants with asthma who took either fluticasone (100 MUg bid), fluticasone
      propionate (100 MUg) + salmeterol (50 MUg) (FP/Salm) or montelukast (5 or 10 mg)
      each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma
      Control Questionnaire (ACQ) scores versus time following randomization; and the
      percent change in percent predicted FEV1 (DeltaFEV1%pred) from enrollment to the
      end of the study. Associations between SNPs and outcomes were analyzed using
      general linear models. False discovery rate and Bonferroni corrections were used
      to correct for multiple comparisons. In all, 16 SNPs in seven genes were
      significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2
      associated with ACQ slope (P=2.8 * 10-5), and rs1461496 in HSPA8 associated with
      DeltaFEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 * 10-4), and three
      SNPs in COL2A1 associated with ACQ slope and DeltaFEV1%pred, respectively. For
      montelukast, four SNPs in CHRM2 associated with DeltaFEV1%pred and predicted an
      opposite effect compared with fluticasone (P=9 * 10-3). The present study
      indentified several novel SNPs that associate with response to common asthma
      controllers, and support further pharmacogenomic study and the use of genetic
      variants to personalize asthma treatment.

PMID- 22370860
TI  - Feline alimentary lymphoma: 1. Classification, risk factors, clinical signs and
      non-invasive diagnostics.
AB  - PRACTICAL RELEVANCE: Alimentary lymphoma (AL) occurs commonly in cats and exists
      as distinct subtypes that differ in their clinical course, response to treatment
      and prognosis. Accurate diagnosis is important to guide appropriate treatment.
      CLINICAL CHALLENGES: Differentiation of low-grade alimentary lymphoma from
      lymphoplasmacytic enteritis can be challenging, especially where endoscopic
      intestinal biopsies, which sample only the mucosa and submucosa, are used. The
      major differentials for intermediate- and high-grade alimentary lymphoma are
      other neoplastic and non-neoplastic intestinal mass lesions. The diagnosis of
      large granular lymphocyte lymphoma requires vigilance as it may be missed with
      routine diagnostics. PATIENT GROUP: AL affects predominantly middle- to old-aged
      domestic crossbred cats (median age 10-13 years). EVIDENCE BASE: The evidence
      supporting this review is grade II, III and IV, derived from prospective studies,
      retrospective case series, reviews, extrapolation from other species,
      pathophysiological justification and the combined clinical experience of those
      working in the field.

PMID- 22370861
TI  - Feline alimentary lymphoma: 2. Further diagnostics, therapy and prognosis.
AB  - PRACTICAL RELEVANCE: Accurate diagnosis of the distinct subtypes of alimentary
      lymphoma (AL) that occur in cats is important as there are major differences
      between them in clinical presentation, treatment and prognosis. Unlike
      intermediate- and high-grade alimentary lymphoma (I/HGAL) and large granular
      lymphocyte lymphoma (LGLL), which can often be diagnosed by aspiration cytology,
      full-thickness intestinal biopsies are usually required for the diagnosis of low
      grade alimentary lymphoma (LGAL). CLINICAL CHALLENGES: LGAL is an increasingly
      recognised clinical problem and it can be challenging to differentiate from
      inflammatory disease. Where there is ambiguity on histology, further diagnostics
      (immunophenotyping and clonality analysis) may be required. The diagnosis of LGLL
      requires an index of suspicion as it may be missed with routine diagnostics.
      While cats with LGAL typically achieve durable remissions with oral prednisolone
      and chlorambucil, I/HGAL runs a more aggressive clinical course and requires
      multi-agent chemotherapeutic protocols. Information on the treatment of LGLL is
      limited and this form of AL has the poorest prognosis. Preliminary studies
      suggest that abdominal irradiation may potentially be of benefit in cats with AL
      and further investigations are warranted. EVIDENCE BASE: The evidence supporting
      this review is derived from grade II, III and IV prospective studies,
      retrospective case series, reviews, extrapolation from other species,
      pathophysiological justification and the combined clinical experience of those
      working in the field.

PMID- 22370862
TI  - Feline lung-digit syndrome: unusual metastatic patterns of primary lung tumours
      in cats.
AB  - PRACTICAL RELEVANCE: Feline 'lung-digit syndrome' describes an unusual pattern of
      metastasis that is seen with various types of primary lung tumours, particularly
      bronchial and bronchioalveolar adenocarcinoma. Tumour metastases are found at
      atypical sites, notably the distal phalanges of the limbs; the weightbearing
      digits are most frequently affected, and multiple-digit and multiple-limb
      involvement is common. Often primary lung tumours in cats are not detected
      because of clinical signs referable to the primary tumour; rather, many cases
      present with signs referable to distant metastases. Other sites of metastases
      from feline primary lung tumours include the skin, eyes, skeletal muscle and
      bone, as well as multiple thoracic and abdominal organs. These lesions are
      thought to arise from direct arterial embolisation from the tumour. Indeed tumour
      embolisation to the aortic trifurcation is possible. PATIENT GROUP: Primary lung
      neoplasms are uncommon in the cat. Older animals are most affected (mean age at
      presentation 12 years, range 2-20 years). There is no apparent sex or breed
      predilection. CLINICAL CHALLENGES: Feline lung-digit syndrome presents a
      diagnostic challenge. Typically there is swelling and reddening of the digit,
      purulent discharge from the nail bed, and dysplasia or fixed exsheathment of the
      associated nail. While these signs might be suggestive of infection, this could
      be secondary to a digital metastatic lesion, particularly in a middle-aged or
      elderly cat. Radiographic evidence of extensive bony lysis of the distal phalanx,
      which can be trans-articular to the second phalanx, raises the index of clinical
      suspicion for metastasis of a primary pulmonary tumour. Thoracic radiography is
      warranted prior to any surgery or digital amputation as the prognosis is
      generally grave for cats with this syndrome, with a mean survival time of only 58
      days after presentation. EVIDENCE BASE: This article reviews the previous
      literature and case reports of feline lung-digit syndrome and feline primary
      pulmonary neoplasia in general, discussing the course of this disease and the
      varying clinical presentations associated with different sites of metastasis.

PMID- 22370863
TI  - Feline demodicosis: a consideration in the itchy or overgrooming cat.
AB  - PRACTICAL RELEVANCE: In cats, three species of demodex mites have been identified
      as causes of demodicosis, which may manifest as pruritus, miliary dermatitis
      and/or self-induced alopecia. The condition has been recognized in various
      countries but does seem to show regional preferences. CLINICAL CHALLENGES:
      Diagnosis of feline demodicosis can be a challenge as mites are not always
      readily found within scrapings of the skin examined microscopically. One or more
      species of demodex mite may be involved in an infestation. Furthermore, the
      condition can be difficult to treat effectively. AUDIENCE: This review is
      intended as a clinical update for veterinary surgeons in practice who rarely
      encounter demodicosis.

PMID- 22370864
TI  - Nanocrystalline silver dressing and subatmospheric pressure therapy following
      neoadjuvant radiation therapy and surgical excision of a feline injection site
      sarcoma.
AB  - CLINICAL SUMMARY: This is the first clinical report of use of a combination of
      nanocrystalline silver and subatmospheric pressure therapy to treat a resistant
      wound infection, following tumour removal and radiation therapy, in a difficult
      to-manage surgical site in a cat. PRACTICAL RELEVANCE: The therapy was well
      tolerated and the authors suggest it is a valid treatment protocol for management
      of non-healing or infected wounds in the cat.

PMID- 22370865
TI  - Lung lobe torsion in association with a chronic diaphragmatic hernia and
      haemorrhagic pleural effusion in a cat.
AB  - CLINICAL SUMMARY: This report describes torsion of the right cranial lung lobe in
      a cat with haemorrhagic pleural effusion and a chronic diaphragmatic hernia.
      Surgical treatment comprising lung lobectomy without de-rotation, and repair of
      the diaphragmatic defect, led to an uneventful recovery. PRACTICAL RELEVANCE:
      Lung lobe torsion is a rare condition in cats. While spontaneous lung lobe
      torsions may occur, a frequent association with underlying thoracic disease has
      been recognised in cats. However, neither haemorrhagic pleural effusion nor
      diaphragmatic hernia have been previously described in cats with lung lobe
      torsions, although they have been documented in dogs and humans. In a cat with
      suspected lung lobe torsion, a thorough search for an underlying disease should
      be undertaken.

PMID- 22370867
TI  - A possible role of the cholinergic and purinergic receptor interaction in the
      regulation of the rat urinary bladder function.
AB  - The contractile activation of the upper (dome) and lower (base) parts of the
      urinary bladder show some differences. Cellular mechanisms that might be
      responsible for cholinergic effects blocking non-adrenergic non-cholinergic
      contractions in the base of the rat urinary bladder were investigated. Smooth
      muscle cells were thus freshly isolated or cultured both from the dome and the
      base of the rat urinary bladder and the contribution from cholinergic and
      purinergic pathways to their Ca(2+) homeostasis was examined. The expression of
      nicotinic acetylcholine (nAChR) and P2X2 purinergic receptors on the cultured
      cells and on tissue sections was investigated. The ATP-evoked Ca(2+) transients
      in rat smooth muscle cells did not show any desensitization. However, when ATP
      was administered together with carbamylcholine (CCh), the latter essentially
      prevented ATP from evoking Ca(2+) transients in smooth muscle cells from the base
      (suppression to 12 +/- 2.5% of control, n = 57; p < 0.01), but not from the dome
      (99 +/- 5% of control, n = 52; p > 0.05) of the rat urinary bladder. While
      atropine was unable to modify (6 +/- 3% of control, n = 14; p < 0.05), alpha
      bungarotoxin (118 +/- 12% of control, n = 20; p > 0.05) blocked the inhibitory
      effects of CCh. Additionally, alpha7 subunits of nAChR and P2X2 purinergic
      receptors were identified using immunocytochemistry, immunohistochemistry, and
      Western blot in cultured urinary bladder smooth muscle cells, in urinary bladder
      sections, and in urinary bladder muscle strips, respectively, suggesting that the
      activation of nAChR modifies the action of ATP.

PMID- 22370868
TI  - New laws of simultaneous contrast?
AB  - Drawing on many seemingly disparate and unrelated lines of evidence, we argue
      that the direction of the simultaneous contrast effect in three-dimensional
      colour space is given by the difference vector between target and surround
      ('direction hypothesis'). This challenges  the traditional idea according to
      which the direction of the simultaneous contrast effect is complementary to the
      colour of the surround ('complementarity law'). We also argue that the size of
      the simultaneous contrast effect is either constant or decreases with the
      difference  between target and surround in three-dimensional colour space. The
      latter proposal challenges Kirschmann's fourth law. Within our theoretical
      framework, the universally presumed validity of the complementarity law and
      Kirschmann's fourth law can be understood as resulting from  the failure to take
      various confounding factors into account when interpreting empirical data, the
      most prominent of which is the influence of temporal von Kries adaptation.

PMID- 22370869
TI  - Evaluation of a scale of patient-reported outcomes for the assessment of
      myasthenia gravis patients in China.
AB  - OBJECTIVE: To evaluate a scale of patient-reported outcomes for the assessment of
      myasthenia gravis patients (MG-PRO) in China. METHODS: A total of 100 MG patients
      were interviewed for the field testing. Another 56 MG patients were selected and
      assessed with the MG-PRO scale before treatment and at 1, 2 and 4 weeks after
      treatment. The classical test theory and item response theory (IRT) were used to
      assess the psychometric characteristics of the MG-PRO scale. RESULTS: The MG-PRO
      scale included 4 dimensions: physical, psychological, social environment, and
      treatment. Confirmatory factor analysis showed that each dimension was consistent
      with the theoretical construct. The scores of the physical and psychological
      dimensions increased significantly at 1 week after treatment (P<0.05). All the
      dimension scores and the MG-PRO score increased significantly at 2 and 4 weeks
      after treatment (P<0.05). IRT showed that person separation indices were greater
      than 0.8, most of the item fit residual statistics were within +/- 2.5, and no
      item had uniform or non-uniform differential item functioning (DIF) between
      gender and age (<40, [Symbol: see text]40). CONCLUSIONS: The MG-PRO scale is
      valid for measuring the quality of life (QOL) of MG patients, with good
      reliability, validity, responsiveness, and good psychometric characteristics from
      IRT. It can be applied to evaluate the QOL of MG patients and to assess treatment
      effects in clinical trials.

PMID- 22370870
TI  - The therapeutic effect of Xiaopi-I on functional dyspepsia.
AB  - OBJECTIVE: To observe the therapeutic efficacy of Xiaopi-I on functional
      dyspepsia and its effects on gastric emptying. METHODS: A total of 134 patients
      with functional dyspepsia were randomly assigned to 2 groups. The patients in the
      Xiaopi-I group (66 cases) and the Domperidone group (68 cases) were given Xiaopi
      I granules and Domperidone 10 mg, 3 times a day, respectively. Another 20 healthy
      volunteers were chosen as the negative control group. The severity scores of the
      symptoms, as well as the gastric emptying, were detected before and after 4-week
      treatment by barium strip-trial meal. RESULTS: During therapy, 6 cases from the
      Xiaopi-I group and 8 cases from the Domperidone group were lost to follow, and
      120 cases finally finished the study. Statistical differences were observed from
      both groups in terms of the symptoms of postprandial fullness early satiety,
      epigastric pain, and epigastric burning after 4-week treatment (P<0.01). The
      symptomatic severity scores of the Xiaopi-I group before and after the treatment
      were 7.48+/-1.64 and 2.16+/-1.26, respectively (P<0.01). Gastric emptying rates
      were also improved in the patients with delayed gastric emptying, and the
      effective rates were 91.3% and 75.8% in the Xiaopi-I and Domperidone groups,
      respectively. No obvious adverse effects were found from both groups. CONCLUSION:
      Xiaopi-I was an effective and safe agent in the treatment of functional dyspepsia
      and was worth of further development in clinical.

PMID- 22370871
TI  - Chinese medicine single-walled carbon nanotube targeting compound for antitumor
      therapy: a feasible way?
AB  - Malignant cancer is the leading cause of death in man, exceeding cerebrovascular
      disease and heart disease. More than half of the total mortality due to malignant
      cancer is from lung, liver, intestinal and gastric cancer. Chemotherapy is one of
      the effective treatments for cancer. However, the great majority of Western
      anticancer medicines have considerable side effects. Herbal medicines offer many
      more advantages than synthesized compounds because they are made from purely
      natural compounds and have less adverse effects. However, the single
      administration methods used as standard in herbal medicine, and deficient drug
      targeting, severely limit their anticancer activity. Single-walled carbon
      nanotubes (SWNTs) can be used as drug carriers. They have been modified to form
      Chinese anticancer medicine-SWNT compounds which can specifically target tumors,
      thereby significantly increasing the therapeutic effectiveness of these
      medicines. Water-soluble SWNTs have high stability. As a drug carrier, SWNTs
      functional modification of the anticancer medicine may improve the targeting and
      killing of tumor cells. SWNTs have been attached to the Chinese antitumor
      medicines paclitaxel and plumbagin and have achieved excellent therapeutic
      effects. Furthermore, choosing the best administration methods such as internal
      iliac arterial infusion, intravesical infusion and embedment of a hypodermic
      chemotherapeutic pump, may also improve the anticancer effects of Chinese
      medicine. 

PMID- 22370872
TI  - Effect of two Chinese medicinal compounds, blood-activating and water-draining
      medicine, on tumor necrosis factor alpha and nuclear factor kappa B expressions
      in rats with intracerebral hemorrhage.
AB  - OBJECTIVE: To investigate the effect of blood-activating Chinese medicinal
      compounds and water-draining Chinese medicinal compounds on tumor necrosis factor
      alpha (TNF-alpha) and nuclear factor kappaB (NF-kappa B) expressions in rats with
      intracerebral hemorrhage (ICH) at the acute stage, and to monitor their
      therapeutic effect and mechanism of action on inflammation and cerebral edema.
      METHODS: A rat model of cerebral hemorrhage was achieved by injecting autologous
      arterial blood into the caudate nucleus. A total of 168 rats were randomly
      divided into 4 groups: blood-activating medicine group (n=42), water-draining
      medicine group (n=42), sham operated group (n=42), and the model group (n=42). A
      series of brain samples were obtained at days 1, 3 and 5 after ICH from rats in
      all groups. Protein expression levels of TNF-alpha and NF-kappa B were measured
      by immunohistochemical staining and gene expression levels of TNF-alpha and NF
      kappa B were measured by real-time fluorescent PCR. RESULTS: Compared to the sham
      operated group, protein expression levels of TNF-alpha and NF-kappa B in the
      model group significantly increased (P<0.01). Protein and gene expressions of TNF
      alpha from the blood-activating medicine group and water-draining medicine group
      significantly decreased when compared to those in the model group P<0.05).
      Meanwhile, compared to the model group, the expression of NF-kappa B in the blood
      activating medicine group significantly decreased (P<0.05), while expression of
      NF-kappa B in the water-draining medicine group did not differ (P>0.05).
      CONCLUSIONS: Blood-activating Chinese medicinal compounds and water-draining
      Chinese medicinal compounds can alleviate inflammation of peripheral tissue and
      cerebral edema. However, the blood-activating Chinese medicinal compounds were
      more effective than the water-draining Chinese medicinal compounds. The possible
      effective mechanism may be by means of inhibiting the activation of NF-kappa B so
      as to suppress the transcription of target genes including gene expression of TNF
      alpha.

PMID- 22370874
TI  - Impaired cerebellar and limbic responses to the valsalva maneuver in heart
      failure.
AB  - Heart failure (HF) patients show an inability to regulate autonomic functions, a
      characteristic which is associated with increased mortality. These autonomic
      deficits may stem from earlier demonstrated injury to central autonomic
      regulatory areas, providing a structural basis for the autonomic abnormalities.
      However, knowledge of structural injury provides insufficient insights into
      timing and magnitude of signal patterns within affected areas which lead to
      impaired autonomic outflow. Among damaged brain areas, cerebellar sites are key
      for timely coordination of sympathetic and parasympathetic attributes, and for
      dampening extremes of hypotension and hypertension induced by other injured
      sites, including hypothalamic and limbic areas. We collected functional magnetic
      resonance imaging (fMRI) signals in cerebellar and limbic areas to characterize
      amplitude and timing patterns of neural responses to the Valsalva maneuver, an
      autonomic challenge that elicits sequential sympathetic and parasympathetic
      responses, in 16 HF patients and 33 control subjects. HF patients showed
      distorted fMRI signal patterns during the challenge period in the cerebellar
      vermis, left cerebellar crus II, and left insula, whereas the right crus II and
      insula, and bilateral amygdalae showed normal patterns. However, all structures,
      except the left crus II, showed altered responses in HF during the recovery
      period. Crus II patterns reflected a failure of HF subjects to demonstrate the
      normal lateralized responses, while in the insula, HF subjects exhibited abnormal
      left-right patterns, relative to controls. The abnormal timing and response
      patterns in these injured areas critical for autonomic regulation likely
      contribute to the enhanced sympathetic outflow and autonomic dysfunction
      characteristic of HF.

PMID- 22370875
TI  - Procoagulant activity of erythrocytes and platelets through phosphatidylserine
      exposure and microparticles release in patients with nephrotic syndrome.
AB  - Recent studies showed that an imbalance of prothrombotic and antithrombotic
      factors and impaired thrombolytic activity contribute to the thrombophilia of the
      nephrotic syndrome (NS). However, it is not clear whether blood cell injury
      and/or activation is involved in hypercoagulability in NS patients. Our
      objectives were to study the increase in microparticle (MP) release and
      phosphatidylserine (PS) exposure on the outer membrane of MP-origin cells in NS
      patients, and to evaluate their procoagulant activity (PCA). The subjects were
      patients with membranous nephropathy (MN), minimal change nephrotic syndrome
      (MCNS) and healthy controls. Analyses of MPs and PS exposure were performed using
      a flow cytometer. PCA was determined by clotting time and purified coagulation
      complex assays. We found that lactadherin+ MPs, which derived from red blood
      cells (RBC), platelet and endothelial cell, increased in NS patients. Moreover,
      PS exposure on RBCs and platelets in each NS group, especially in MN, are higher
      than that in controls. MP shedding and PS exposure of RBCs/platelets were highly
      procoagulant in NS patients. However, blockade of PS with lactadherin inhibited
      over 90% of PCA while an anti-tissue factor antibody had no significant
      inhibition effect. Our results demonstrate that the thrombophilic susceptibility
      of NS may be partly ascribed to MP release and PS exposure of RBCs, platelets and
      endothelial cells. Lactadherin is a sensitive probe for PS that has high
      anticoagulant activity.

PMID- 22370876
TI  - Identification of nitrite-reducing bacteria using sequential mRNA fluorescence in
      situ hybridization and fluorescence-assisted cell sorting.
AB  - Sequential mRNA fluorescence in situ hybridization (mRNA FISH) and fluorescence
      assisted cell sorting (SmRFF) was used for the identification of nitrite-reducing
      bacteria in mixed microbial communities. An oligonucleotide probe labeled with
      horseradish peroxidase (HRP) was used to target mRNA of nirS, the gene that
      encodes nitrite reductase, the enzyme responsible for the dissimilatory reduction
      of nitrite to nitric oxide. Clones for nirS expression were constructed and used
      to provide proof of concept for the SmRFF method. In addition, cells from pure
      cultures of Pseudomonas stutzeri and denitrifying activated sludge were
      hybridized with the HRP probe, and tyramide signal amplification was performed,
      conferring a strongly fluorescent signal to cells containing nirS mRNA. Flow
      cytometry-assisted cell sorting was used to detect and physically separate two
      subgroups from a mixed microbial community: non-fluorescent cells and an
      enrichment of fluorescent, nitrite-reducing cells. Denaturing gradient gel
      electrophoresis (DGGE) and subsequent sequencing of 16S ribosomal RNA (rRNA)
      genes were used to compare the fragments amplified from the two sorted subgroups.
      Sequences from bands isolated from DGGE profiles suggested that the dominant,
      active nitrite reducers were closely related to Acidovorax BSB421. Furthermore,
      following mRNA FISH detection of nitrite-reducing bacteria, 16S rRNA FISH was
      used to detect ammonia-oxidizing and nitrite-oxidizing bacteria on the same
      activated sludge sample. We believe that the molecular approach described can be
      useful as a tool to help address the longstanding challenge of linking function
      to identity in natural and engineered habitats.

PMID- 22370878
TI  - Single electron tunneling in large scale nanojunction arrays with bisferrocene
      nanoparticle hybrids.
AB  - We report on the fabrication and single electron tunneling behaviour of large
      scale arrays of nanogap electrodes bridged by bisferrocene-gold nanoparticle
      hybrids (BFc-AuNP). Coulomb staircase was observed in the low temperature current
      voltage curves measured on the junctions with asymmetric tunnel barriers. On the
      other hand, junctions with symmetric tunneling barrier exhibited mere nonlinear
      current voltage characteristics without discrete staircase. The experimental
      results agreed well with simulations based on the orthodox theory. The junction
      resistance showed thermally activated conduction behaviour at higher temperature.
      The overall voltage and temperature dependent results show that the transport
      behaviour of the large arrays of single particle devices obtained by a facile
      optical lithography and chemical etching process corresponds with the behaviour
      of single particle devices fabricated by other techniques like e-beam lithography
      and mechanical breaking methods.

PMID- 22370877
TI  - The distribution of Francisella-like bacteria associated with coastal waters in
      Norway.
AB  - We report the diversity and distribution of Francisella species in Norwegian
      coastal and fresh waters following a nationwide survey in which water and
      sediment samples were collected from locations spanning almost the entire
      Norwegian coastline. In total, samples were obtained from 149 and 64 seawater and
      freshwater sites, respectively. DNA extracts from these environmental samples
      were initially screened by polymerase chain reaction (PCR) using Francisella
      genus-specific 16S rDNA primers. Positive samples were then amplified with genus
      specific primers targeting Francisella succinate dehydrogenase A gene and
      Francisella philomiragia group-specific sequences for the SAICAR
      synthetase/phosphoribosylamine-glycine ligase gene. Francisella-related bacteria
      were identified in approximately 30% of seawater sampled sites, mainly in
      southern Norway, although a single positive sample was identified in the far
      north of the country. No PCR positives were identified from the freshwater
      sources. Sequences related to recognised species, both pathogenic and
      environmental, were identified, with the majority closely associated with F.
      philomiragia. However, a number of identified sequences probably represent
      previously undescribed species. Our data provide evidence of a significant
      background of Francisella spp. in geographical areas associated with outbreaks of
      fish francisellosis in Norway.

PMID- 22370873
TI  - Consensus paper: pathological role of the cerebellum in autism.
AB  - There has been significant advancement in various aspects of scientific knowledge
      concerning the role of cerebellum in the etiopathogenesis of autism. In the
      current consensus paper, we will observe the diversity of opinions regarding the
      involvement of this important site in the pathology of autism. Recent emergent
      findings in literature related to cerebellar involvement in autism are discussed,
      including: cerebellar pathology, cerebellar imaging and symptom expression in
      autism, cerebellar genetics, cerebellar immune function, oxidative stress and
      mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic,
      dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control
      and cognitive deficits, cerebellar coordination of movements and cognition, gene
      environment interactions, therapeutics in autism, and relevant animal models of
      autism. Points of consensus include presence of abnormal cerebellar anatomy,
      abnormal neurotransmitter systems, oxidative stress, cerebellar motor and
      cognitive deficits, and neuroinflammation in subjects with autism. Undefined
      areas or areas requiring further investigation include lack of treatment options
      for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as
      a consistent feature of autism, mechanisms underlying cerebellar contributions to
      cognition, and unknown mechanisms underlying neuroinflammation.

PMID- 22370880
TI  - Multiplex PCR panel of microsatellite markers for the  tambaqui, Colossoma
      macropomum, developed as a tool for use in conservation and  broodstock
      management.
AB  - The  tambaqui, Colossoma macropomum, native to Brazil, is widely used in 
      aquaculture systems. We developed a multiplex PCR panel for this species, 
      comprising 12 microsatellite loci. This panel was used to genotype 73 specimens 
      collected from Juruti, a city in the Brazilian Amazon. The mean number of 
      alleles per locus was 8.8, the mean observed heterozygosity was 0.76, and the 
      combined power of discrimination and the combined power of exclusion were 
      0.99999999999999993 and 0.999991762, respectively. We observed no significant 
      deviation from Hardy-Weinberg equilibrium in this population. All amplified 
      alleles were clearly typed, and easily interpretable results were obtained.  This
      method will be useful for paternity analysis, population genetics and 
      conservation studies, as well as for selective breeding programs for C. 
      macropomum.

PMID- 22370879
TI  - Plant potassium content modifies the effects of arbuscular mycorrhizal symbiosis
      on root hydraulic properties in maize plants.
AB  - It is well known that the arbuscular mycorrhizal (AM) symbiosis helps the host
      plant to overcome several abiotic stresses including drought. One of the
      mechanisms for this drought tolerance enhancement is the higher water uptake
      capacity of the mycorrhizal plants. However, the effects of the AM symbiosis on
      processes regulating root hydraulic properties of the host plant, such as root
      hydraulic conductivity and plasma membrane aquaporin gene expression, and protein
      abundance, are not well defined. Since it is known that K(+) status is modified
      by AM and that it regulates root hydraulic properties, it has been tested how
      plant K(+) status could modify the effects of the symbiosis on root hydraulic
      conductivity and plasma membrane aquaporin gene expression and protein abundance,
      using maize (Zea mays L.) plants and Glomus intraradices as a model. It was
      observed that the supply of extra K(+) increased root hydraulic conductivity only
      in AM plants. Also, the different pattern of plasma membrane aquaporin gene
      expression and protein abundance between AM and non-AM plants changed with the
      application of extra K(+). Thus, plant K(+) status could be one of the causes of
      the different observed effects of the AM symbiosis on root hydraulic properties.
      The present study also highlights the critical importance of AM fungal aquaporins
      in regulating root hydraulic properties of the host plant.

PMID- 22370881
TI  - Circulatory microRNA-145 expression is increased in cerebral ischemia.
AB  - Cerebral  ischemia or ischemic stroke is mainly attributed to vascular and
      circulation  disorders. Among protein biomarkers, RNA profiles have also been
      identified as  markers of ischemic stroke. MicroRNA-145 expression is ostensibly
      recognized as  marker and modulator of vascular smooth muscle cell phenotype;
      however,  expression levels in ischemic stroke had not been investigated.
      Employing  real-time quantitative PCR, we examined the expression profile of
      circulatory  microRNA-145 in healthy control subjects (N = 14) and ischemic
      stroke patients  (N = 32). Circulatory microRNA-145 expression was significantly
      higher in  ischemic stroke patients than in control subjects. This demonstrates
      that  hemostatic mechanisms are affected by ischemic stroke. We conclude that 
      circulating microRNA-145 has potential as a biomarker for ischemic stroke.

PMID- 22370882
TI  - Immunohistochemical and molecular analysis of  caveolin-1 expression in canine
      mammary tumors.
AB  - Caveolin-1 (Cav-1) is a structural protein present in  invaginations of the cell
      membrane. In human breast cancer, the cav-1 gene  is believed to be a tumor
      suppressor gene associated with inhibition of tumor  metastasis. However, little
      is known about its expression, regulation and  function in canine mammary tumors.
      Expression levels of cav-1 were  investigated using real-time PCR and
      immunohistochemical detection with an  anti-human Cav-1 antibody. Gene expression
      stability of different samples was  analyzed using the geNorm software. Mammary
      tumors from 51 female dogs were compared  to normal mammary tissue from 10 female
      dogs. Malignant mammary cells showed a  loss of Cav-1 expression by quantitative
      RT-PCR and weak Cav-1 staining  by immunohistochemistry compared to normal
      mammary gland tissue. There was a  significant relationship between outcome and
      immunostaining as well as with  tumor size, indicating that caveolin
      subexpression has a positive predictive  value and is related to higher survival
      and smaller tumor size. Our findings  indicate that Cav-1 is a potential
      prognostic marker for canine mammary tumors.

PMID- 22370884
TI  - Improved method for predicting protein fold patterns  with ensemble classifiers.
AB  - Protein folding is recognized as a critical problem in  the field of biophysics
      in the 21st century. Predicting protein-folding  patterns is challenging due to
      the complex structure of proteins. In an attempt  to solve this problem, we
      employed ensemble classifiers to improve prediction  accuracy. In our
      experiments, 188-dimensional features were extracted based on  the composition
      and physical-chemical property of proteins and 20-dimensional  features were
      selected using a coupled position-specific scoring matrix.  Compared with
      traditional prediction methods, these methods were superior in  terms of
      prediction accuracy. The 188-dimensional feature-based method achieved  71.2%
      accuracy in five cross-validations. The accuracy rose to 77% when we used  a 20
      dimensional feature vector. These methods were used on recent data, with  54.2%
      accuracy. Source codes and dataset, together with web server and software  tools
      for prediction, are available at: 
      http://datamining.xmu.edu.cn/main/~cwc/ProteinPredict.html.

PMID- 22370883
TI  - Carcass composition and meat quality of indigenous Yanan pigs of China.
AB  - The Yanan (YN) pig is a traditional Chinese indigenous  breed that is raised in
      southwest China in the Sichuan Province, but there is  little data on the
      germplasm characteristics of this breed. To evaluate carcass  characteristics and
      meat quality of the YN pig, we compared carcass and meat  quality of YN pigs and
      Landrace * Yanan (CY) hybrid pigs; 30 YN pigs and 30 CY  pigs weighing 20 +/- 2
      kg were reared and slaughtered at the normal slaughter  weight (100-120 kg). The
      carcasses were chilled and the left carcass side was  dissected into bone, lean
      meat, fat, and skin; meat quality parameters were  measured. Carcasses of YN pigs
      were lighter (88.85 vs 90.05 kg, P <  0.05) and shorter (71.88 vs 77.61 cm, P <
      0.001); they contained less  lean meat (41.60 vs 49.25%, P < 0.001), less ham and
      breech (25.93 vs 27.53%, P < 0.001) and less carcass bone (9.83 vs 10.53%, P < 
      0.01) than did carcasses of CY pigs. On the other hand, YN pigs had more  carcass
      subcutaneous fat and skin (48.58 vs 40.23%, P < 0.001),  thicker backfat (3.67 vs
      3.43 cm, P < 0.001) and smaller loin muscle  area (9.83 vs 26.91 cm(2), P  <
      0.001) compared with CY pigs. Among meat quality parameters, YN pigs had  higher
      pH(1) (6.41 vs 6.17, P < 0.001),  higher color score(u) (3.86 vs 3.36, P < 0.001)
      and  lower Minolta L(u) values (40.89 vs 45.32, P <  0.01) than CY pigs. On the
      other hand, YN pigs had lower drip loss (1.31 vs 2.26%,  P < 0.05) and lesser
      fiber area (2351.34 vs 3025.43 MUm(2), P < 0.01) than CY pigs. Both breeds had
      high intramuscular fat  (4.46% in YN and 4.45% in CY). No significant differences
      in other carcass  traits and meat quality were found in the two populations. We
      conclude that YN  pigs could be used in commercial pig production to provide good
      tasting and  high-quality niche products.

PMID- 22370885
TI  - A simple boiling-based DNA  extraction for RAPD profiling of landfarm soil to
      provide representative  metagenomic content.
AB  - Landfarm  soils are employed in industrial and petrochemical residue
      bioremediation. This  process induces selective pressure directed towards
      microorganisms capable of  degrading toxic compounds. Detailed description of
      taxa in these environments  is difficult due to a lack of knowledge of culture
      conditions required for  unknown microorganisms. A metagenomic approach permits
      identification of  organisms without the need for culture. However, a DNA
      extraction step is first  required, which can bias taxonomic representativeness
      and interfere with  cloning steps by extracting interference substances. We
      developed a simplified  DNA extraction procedure coupled with metagenomic DNA
      amplification in an  effort to overcome these limitations. The amplified
      sequences were used to  generate a metagenomic data set and the taxonomic and
      functional  representativeness were evaluated in comparison with a data set built
      with DNA  extracted by conventional methods. The simplified and optimized method
      of RAPD  to access metagenomic information provides better representativeness of
      the  taxonomical and metabolic aspects of the environmental samples.

PMID- 22370886
TI  - Detection by denaturing gradient gel electrophoresis of ammonia-oxidizing
      bacteria in microcosms of crude oil-contaminated mangrove sediments.
AB  - Currently,  the effect of crude oil on ammonia-oxidizing bacterium communities
      from  mangrove sediments is little understood. We studied the diversity of 
      ammonia-oxidizing bacteria in mangrove microcosm experiments using mangrove 
      sediments contaminated with 0.1, 0.5, 1, 2, and 5% crude oil as well as  non
      contaminated control and landfarm soil from near an oil refinery in Camamu  Bay
      in Bahia, Brazil. The evolution of CO(2) production in all  crude oil
      contaminated microcosms showed potential for mineralization. Cluster  analysis of
      denaturing gradient gel electrophoresis-derived samples generated  with primers
      for gene amoA, which encodes the functional enzyme ammonia  monooxygenase, showed
      differences in the sample contaminated with 5% compared  to the other samples.
      Principal component analysis showed divergence of the  non-contaminated samples
      from the 5% crude oil-contaminated sediment. A Venn  diagram generated from the
      banding pattern of PCR-denaturing gradient gel  electrophoresis was used to look
      for operational taxonomic units (OTUs) in  common. Eight OTUs were found in non
      contaminated sediments and in samples  contaminated with 0.5, 1, or 2% crude oil.
      A Jaccard similarity index of 50%  was found for samples contaminated with 0.1,
      0.5, 1, and 2% crude oil. This is  the first study that focuses on the impact of
      crude oil on the  ammonia-oxidizing bacterium community in mangrove sediments
      from Camamu Bay.

PMID- 22370888
TI  - Genetic and biochemical  differentiation in Vitis vinifera (Kabarcik) populations
      grown at  different altitudes in Coruh Valley.
AB  - We  examined genetic differences of four Vitis vinifera populations (A, B,  C, D)
      including local Kabarcik cultivar grown along an altitude gradient of  800, 900,
      1000, and 1150 m above sea level in the Coruh Valley (800 m: A  population; 900
      m: B population; 1000 m: C population; 1150 m: D population).  Leaf samples were
      used for both RAPD and fatty acid analysis. A total of 60  individuals with 15
      individuals per population were included in this study.  RAPD analyses showed
      various band sizes, which ranged from 250 to 3000 bp. Mean  polymorphic locus
      ratios were determined as 96.29% considering four  populations. The highest
      percentage of polymorphic loci (97.8%) was produced by  the highest altitude.
      Thirty-two different fatty acids were found; linoleic  acid was the most common
      in all four populations. According to the dendograms  obtained from statistical
      analyses of RAPD and fatty acid profiles the  populations that were close to each
      other in terms of geographical distance  also were similar genetically.

PMID- 22370887
TI  - Are bone mineral density loci  associated with hip osteoporotic fractures? A
      validation study on previously  reported genome-wide association loci in a
      Chinese population.
AB  - Osteoporosis  is a heritable disease characterized mainly by low bone mineral
      density (BMD)  and/or osteoporotic fractures (OF). Most genome-wide association
      studies on  osteoporosis have focused on BMD, whereas little effort has been
      expended to  identify genetic variants directly linked to OF. To determine
      whether BMD-loci  are also associated with OF risk, we performed a validation
      study to examine 23  BMD-loci reported by recent genome-wide association studies
      for association  with hip OF risk. Our sample consisted of 700 elderly Chinese
      Han subjects, 350  with hip OF and 350 healthy matched controls. We identified
      four BMD-loci that  were significantly associated with hip OF in this Chinese
      population, including  7q21 (FLJ42280, P = 1.17 * 10(-4) for rs4729260; P = 
      0.008 for rs7781370), 6p21 (MHC, P = 0.004 for rs3130340), 13q14 (TNFSF11,  P =
      0.012 for rs9533090; P = 0.018 for rs9594759; P = 0.020 for rs9594738; P =  0.044
      for rs9594751), and 18q21 (TNFRSF11A, P = 0.015 for rs884205). The  SNP rs4729260
      at 7q21 remained significantly associated, even after  conservative Bonferroni's
      correction. Our results further highlight the  importance of these loci in the
      pathogenesis of osteoporosis, and demonstrate  that it is feasible and useful to
      use OF as the direct phenotype to conduct  genetic studies, to enhance our
      understanding of the genetic architecture of  osteoporosis.

PMID- 22370889
TI  - Association between HLA-A and -B polymorphisms and susceptibility to Henoch
      Schonlein purpura in Han and Mongolian children from Inner Mongolia.
AB  - We examined a possible association between HLA-A and  -B polymorphisms and
      susceptibility to Henoch-Schonlein purpura (HSP) in Han  and Mongolian children
      in Inner Mongolia, through a case-control study. Two  hundred and sixty-eight
      unrelated children were enrolled, including 56  Mongolian and 50 Han children
      with HSP, 66 healthy Mongolian and 96 healthy Han  children as a control group.
      HLA-A and -B alleles were indentified by  PCR-sequence-specific oligonucleotide
      analysis and were further analyzed by  PCR-sequencing-based typing (SBT).
      Frequencies of HLA-A*11, HLA-B*15 in  Mongolian patients and HLA-A*26, HLA-B*35,
      HLA-B*52 in Han patients were higher  than those in the corresponding control
      group (P < 0.05), while frequencies  of HLA-B*07 and -B*40 in Mongolian HSP
      patients were lower than those in the  control group (P < 0.05). Further analysis
      using PCR-SBT showed that all  HLA-A*11 were HLA-A*1101, and most HLA-B*15 were
      HLA-B*1501 in Mongolian HSP  patients. All HLA-A*26 were HLA-A*2601 and HLA-B*35
      were mostly HLA-B*3503 in  Han patients. There were more Han patients with severe
      manifestations than  Mongolian patients (P < 0.05). Frequencies of HLA-A*26, HLA
      B*35 and HLA-B*52  in Han patients were higher than in Mongolian patients (P <
      0.05). We  conclude that HLA-A*11(*1101) and -B*15(*1501) are associated with 
      susceptibility to HSP in Mongolian children and HLA-A*26(*2601),  HLA-B*35(*3503)
      and HLA-B*52 are associated with susceptibility to HSP in Han  children. HLA-B*07
      and -B*40 may be protective genes in Mongolian children. The  different
      frequencies of HLA-A and -B in Mongolian and Han children may be  responsible for
      the different manifestations in these two ethnic groups.

PMID- 22370890
TI  - Leaf morphological and genetic divergence in  populations of Drimys (Winteraceae)
      in Chile.
AB  - The genus Drimys is distributed in Chile from  semi-arid zones to sub-Antarctic
      forests; there are three species of this tree, D. andina, D. confertifolia and D.
      winteri, the latter  with varieties chilensis and winteri. Northern populations
      are  found in small disjunct natural refuges, specifically mountain cloud forests
      and the bottom of ravines. The size and continuity of populations are greater 
      in the south, where wetter conditions prevail. Morphological differences  between
      populations have been observed, particularly between the northern  populations of
      Fray Jorge and Talinay. This observation, led to the following  questions: a)
      what is the level of morphological and genetic divergence among  the populations
      of Drimys in Chile? and b) do the populations from Fray  Jorge/Talinay, currently
      classified as D. winteri var. chilensis,  differ genetically from the other
      populations of this variety? To answer these  questions, we collected leaf
      samples from 37 populations of all Chilean Drimys,  performed leaf morphology
      analysis and estimated genetic divergence using RAPD  markers. We found a high
      degree of leaf morphological and genetic divergence  between the populations of
      Fray Jorge/Talinay and the other Chilean species of Drimys.  The morphological
      and genetic divergence among varieties of D. winteri was  greater than that among
      the species of Drimys, which may indicate  problems with their taxonomic
      classification.

PMID- 22370891
TI  - Improved production of transgenic Dioscorea  zingiberensis (Dioscoreaceae) by
      Agrobacterium tumefaciens-mediated  transformation.
AB  - The establishment of high-efficiency Agrobacterium-mediated  transformation
      techniques could improve the production of Dioscorea  zingiberensis, a medicinal
      species with a high diosgenin content. We  co-cultivated embryogenic calli
      induced from mature seeds with A.  tumefaciens strain EHA105. A binary vector,
      pCAMBIA1381, which contains the gfp and hpt genes under the control of the
      ubiquitin promoter and  the CaMV 35S promoter, respectively, was used for
      transformation. Pre-culture,  basic medium, acetosyringone, and bacterial density
      were evaluated to establish  the most efficient protocol. The optimal conditions
      consisted of MS medium  without CaCl(2) for pre- and co-cultivation, three days 
      for pre-culture, addition of 200 MUM AS, and an OD(600) of 0.5. The transgenic
      plants grown under selection  were confirmed by PCR analysis and Southern blot
      analysis. This protocol  produced transgenic D. zingiberensis plants in seven
      months, with a  transformation efficiency of 6%.

PMID- 22370892
TI  - Analysis of genetic distance  by SSR in waxy maize.
AB  - We  examined the genetic diversity of 80 inbred waxy maize lines using 22 SSR 
      molecular markers that could be used to achieve heterosis in waxy maize. Eighty 
      inbred waxy maize lines with different phenotypes, 40 yellow, 25 white, 13 
      black, and two red lines were analyzed by SSR molecular marker fingerprint and 
      cluster analysis. Using a standard genetic distance of 0.55, the 80 waxy maize 
      inbred lines were clustered into nine groups. Among them, group II, group V, 
      groups VII and VIII, and group IX were divided into three subgroups at a  genetic
      distance of 0.46, into two subgroups at 0.49, into two subgroups at  0.46, and
      into four subgroups at 0.493, respectively. All but one of the yellow  waxy maize
      inbred lines were clustered in groups VI, VII, VIII, and IX. Group  IX (30 lines)
      contained 28 yellow lines; the other 11 yellow lines were  distributed among
      groups VI, VII and VIII. Among the 25 white lines, 21 were clustered  in groups
      III, V, VI and the third subgroup of group II. The black line N72 was  in a group
      of its own. The black lines N75, N76 and N78 were distributed in  groups VII,
      VIII and IX, respectively. The other nine black lines were  clustered in group
      II. The red lines were distributed in the second subgroup of  group II and there
      was no difference in genetic distance between them. In  conclusion, there were
      considerable genetic differences among waxy maize inbred  lines of different
      colors. The mean genetic distance of inbred lines of the  same color was
      significantly less than that of lines of different colors.  Therefore, we
      concluded that it was more accurate to determine the difference  between the
      populations using the highly stable DNA genetic markers.

PMID- 22370893
TI  - Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor
      microRNAs to promote liver cancer metastasis.
AB  - Epigenetic alterations and microRNA (miRNA) deregulation are common in
      hepatocellular carcinoma (HCC). The histone H3 lysine 27 (H3K27) tri-methylating
      enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene
      expression and is frequently up-regulated in human cancers. In this study we
      aimed to delineate the implications of EZH2 up-regulation in miRNA deregulation
      and HCC metastasis. Expressions of a total of 90 epigenetic regulators were first
      determined in 38 pairs of primary HCCs and their corresponding nontumorous
      livers. We identified EZH2 and its associated polycomb repressive complex 2
      (PRC2) as one of the most significantly deregulated epigenetic regulators in
      primary HCC samples. Up-regulation of EZH2 was next confirmed in 69.5% (41/59) of
      primary HCCs. Clinicopathologically, EZH2 up-regulation was associated with HCC
      progression and multiple HCC metastatic features, including venous invasion (P =
      0.043), direct liver invasion (P = 0.014), and absence of tumor encapsulation (P
      = 0.043). We further demonstrated that knockdown of EZH2 in HCC cell lines
      reduced the global levels of tri-methylated H3K27, and suppressed HCC motility in
      vitro and pulmonary metastasis in a nude mouse model. By interrogating the miRNA
      expression profile in EZH2-knockdown cell lines and primary HCC samples, we
      identified a subset of miRNA that was epigenetically suppressed by EZH2 in human
      HCC. These included well-characterized tumor-suppressor miRNAs, such as miR-139
      5p, miR-125b, miR-101, let-7c, and miR-200b. Pathway enrichment analysis revealed
      a common regulatory role of these EZH2-silenced miRNAs in modulating cell
      motility and metastasis-related pathways. Our findings suggest that EZH2 exerts
      its prometastatic function by way of epigenetic silencing of multiple tumor
      suppressor miRNAs. CONCLUSION: Our study demonstrated that EZH2 epigenetically
      silenced multiple miRNAs that negatively regulate HCC metastasis.

PMID- 22370894
TI  - Characteristics of homeless adults with serious mental illnesses served by three
      street-level federally funded homelessness programs.

PMID- 22370895
TI  - Maternal mortality: changing etiologies will require different approaches.

PMID- 22370896
TI  - Transplacental transmission of Cryptococcus neoformans to an HIV-exposed
      premature neonate.
AB  - Cryptococcosis during pregnancy is well documented, but transmission of infection
      to the fetus is rare. We describe a premature neonate born to a mother with
      congenitally acquired human immunodeficiency virus (HIV) and active
      cryptococcosis. Histological examination of the placenta revealed Cryptococcus
      neoformans within the maternal intervillous space with focal invasion into the
      chorionic villi. A positive serum cryptococcal antigen (1:2) was detected on days
      1 and 5 of life. The neonate had no evidence of central nervous system disease
      and was treated with fluconazole with resolution of antigenemia. This case
      highlights both the potential for transplacental transmission of C. neoformans
      infection and the complexities of caring for pregnant mothers who themselves are
      congenitally infected with HIV.

PMID- 22370897
TI  - A neonate with the Pelger-Huet anomaly, cleft lip and palate, and agenesis of the
      corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12.
AB  - We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the
      corpus callosum, slightly small penis, hypoglycemia, and what initially appeared
      to be a marked leukocyte 'left shift' on complete blood count, but which was
      actually a Pelger-Huet anomaly. A chromosomal microdeletion was identified at1q41
      42.12.

PMID- 22370898
TI  - A cystic pulmonary lesion in an infant.

PMID- 22370899
TI  - More on professionals' attitudes on blood-tinged milk: a survey from Italy.

PMID- 22370900
TI  - Importance of electrostatic polarizability in calculating cysteine acidity
      constants and copper(I) binding energy of Bacillus subtilis CopZ.
AB  - CopZ is a copper chaperone from Bacillus subtilis. It is an important part of
      Cu(I) trafficking. We have calculated pK(a) values for the CXXC motif of this
      protein, which is responsible for the Cu(I) binding, and the Cu(I) binding
      constants. Polarizable and fixed-charges formalisms were used, and solvation
      parameters for the both models have been refitted. We had to partially redevelop
      parameters for the protonated and deprotonated cysteine residues. We have
      discovered that the polarizable force field (PFF) is qualitatively superior and
      allows a uniformly better level of energetic results. The PFF pK(a) values for
      cysteine are within about 0.8-2.8 pH units of the experimental data, while the
      fixed-charges OPLS formalism yields errors of up to tens of units. The PFF
      magnitude of the copper binding energy is about 10 kcal/mol or 50% higher than
      the experimental value, while the using the refitted OPLS parameters leads to an
      overall positive binding energy, thus predicting no thermodynamically stable
      complex. At the same time, the agreement of the polarizable S...Cu(I) distances
      with the experimental results is within 0.08 A range, and the nonpolarizable
      calculations lead to an error of about 0.4 A. Moreover, the accuracy of the PFF
      has been achieved without any explicit fitting to either pK(a) or CopZ...Cu(I)
      binding energies. We believe that this makes our polarizable technique a choice
      method in reproducing protein-copper binding and further supports the notion that
      explicit treatment of electrostatic polarization is crucial in many biologically
      relevant studies, especially ion binding and transport.

PMID- 22370901
TI  - Predicting acute kidney injury among burn patients in the 21st century:  a
      classification and regression tree analysis.
AB  - Historically, acute kidney injury (AKI) carried a deadly prognosis in the burn
      population. The aim of this study is to provide a modern description of AKI in
      the burn population and to develop a prediction tool for identifying patients at
      risk for late AKI. A large multi-institutional database, the Glue Grant's Trauma
      Related Database, was used to characterize AKI in a cohort of critically ill burn
      patients. The authors defined AKI according to the RIFLE criteria and categorized
      AKI as early, late, or progressive. They then used Classification and Regression
      Tree (CART) analysis to create a decision tree with data obtained from the first
      48 hours of admission to predict which subset of patients would develop late AKI.
      The accuracy of this decision tree was tested in a separate, single-institution
      cohort of burn patients who met the same criteria for entry into the Glue Grant
      study. Of the 220 total patients analyzed from the Glue Grant cohort, 49 (22.2%)
      developed early AKI, 39 (17.7%) developed late AKI, and 16 (7.2%) developed
      progressive AKI. The group with progressive AKI was statistically older, with
      more comorbidities and with the worst survival when compared with those with
      early or late AKI. Using CART analysis, a decision tree was developed with an
      overall accuracy of 80% for the development of late AKI for the Glue Grant
      dataset. The authors then tested this decision tree on a smaller dataset from our
      own institution to validate this tool and found it to be 73% accurate. AKI is
      common in severe burns with notable differences between early, late, and
      progressive AKI. In addition, CART analysis provided a predictive model for early
      identification of patients at highest risk for developing late AKI with proven
      clinical accuracy.

PMID- 22370902
TI  - MALDI imaging mass spectrometry of neuropeptides in Parkinson's disease.
AB  - MALDI imaging mass spectrometry (IMS) is a powerful approach that facilitates the
      spatial analysis of molecular species in biological tissue samples(2) (Fig.1). A
      12 MUm thin tissue section is covered with a MALDI matrix, which facilitates
      desorption and ionization of intact peptides and proteins that can be detected
      with a mass analyzer, typically using a MALDI TOF/TOF mass spectrometer.
      Generally hundreds of peaks can be assessed in a single rat brain tissue section.
      In contrast to commonly used imaging techniques, this approach does not require
      prior knowledge of the molecules of interest and allows for unsupervised and
      comprehensive analysis of multiple molecular species while maintaining high
      molecular specificity and sensitivity(2). Here we describe a MALDI IMS based
      approach for elucidating region-specific distribution profiles of neuropeptides
      in the rat brain of an animal model Parkinson's disease (PD).     PD is a common
      neurodegenerative disease with a prevalence of 1% for people over 65 of age(3,4).
      The most common symptomatic treatment is based on dopamine replacement using L
      DOPA(5). However this is accompanied by severe side effects including involuntary
      abnormal movements, termed L-DOPA-induced dyskinesias (LID)(1,3,6). One of the
      most prominent molecular change in LID is an upregulation of the opioid precursor
      prodynorphin mRNA(7). The dynorphin peptides modulate neurotransmission in brain
      areas that are essentially involved in movement control(7,8). However, to date
      the exact opioid peptides that originate from processing of the neuropeptide
      precursor have not been characterized. Therefore, we utilized MALDI IMS in an
      animal model of experimental Parkinson's disease and L-DOPA induced dyskinesia.  
      MALDI imaging mass spectrometry proved to be particularly advantageous with
      respect to neuropeptide characterization, since commonly used antibody based
      approaches targets known peptide sequences and previously observed post
      translational modifications.  By contrast MALDI IMS can unravel novel peptide
      processing products and thus reveal new molecular mechanisms of neuropeptide
      modulation of neuronal transmission. While the absolute amount of neuropeptides
      cannot be determined by MALDI IMS, the relative abundance of peptide ions can be
      delineated from the mass spectra, giving insights about changing levels in health
      and disease. In the examples presented here, the peak intensities of dynorphin B,
      alpha-neoendorphin and substance P were found to be significantly increased in
      the dorsolateral, but not the dorsomedial, striatum of animals with severe
      dyskinesia involving facial, trunk and orolingual muscles (Fig. 5). Furthermore,
      MALDI IMS revealed a correlation between dyskinesia severity and levels of des
      tyrosine alpha-neoendorphin, representing a previously unknown mechanism of
      functional inactivation of dynorphins in the striatum as the removal of N
      terminal tyrosine reduces the dynorphin's opioid-receptor binding capacity(9).
      This is the first study on neuropeptide characterization in LID using MALDI IMS
      and the results highlight the potential of the technique for application in all
      fields of biomedical research.

PMID- 22370903
TI  - Prognostic significance of peritoneal lavage cytology in patients with colorectal
      cancer.
AB  - BACKGROUND: The clinical significance of peritoneal lavage cytology for patients
      with gastric cancer is recognized, whereas that for patients with colorectal
      cancer remains controversial. The present study used a nationwide registry to
      clarify the prognostic significance of peritoneal lavage cytology in patients
      with colorectal cancer. METHODS: We retrospectively analyzed factors associated
      with recurrence and survival in patients with T3-T4 colorectal cancer without
      distant metastasis taken from the nationwide registry of the Japanese Society for
      Cancer of the Colon and Rectum between 1984 and 1999. RESULTS: Among 34,554
      patients in this study, not all of whom received peritoneal lavage cytology, 35
      had positive peritoneal lavage cytology. Gender (P = 0.0004), tumor location (P <
      0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001),
      lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.015) were risk
      factors for peritoneal recurrence. Multivariate analysis revealed that tumor
      location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion
      (P < 0.0001) and lymph node metastasis (P < 0.0001) were independent risk factors
      for peritoneal metastasis. Gender (P < 0.0001), tumor location (P < 0.0001), age
      (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P <
      0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.0004)
      were independent prognostic factors according to the Cox proportional hazards
      model. CONCLUSION: Positive peritoneal lavage cytology was associated with poorer
      survival in patients with stage II and III colorectal cancer. Positive cytology
      might be a good indicator of candidates for intensive adjuvant chemotherapy. The
      benefit of intensive adjuvant chemotherapy for such patients should be validated
      in prospective trials.

PMID- 22370904
TI  - Very long-term follow-up results of imatinib mesylate therapy in chronic phase
      chronic myeloid leukemia after failure of interferon alpha therapy.
AB  - BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid
      leukemia treated with imatinib after failure of interferon alpha therapy has not
      been detailed. METHODS: In total, 368 patients were analyzed. Univariate and
      multivariate survival analyses were conducted using standard statistical methods.
      RESULTS: Overall, 247 patients (67%) achieved a complete cytogenetic response
      (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major
      molecular response (MMR), and 99 patients (30%) had undetectable breakpoint
      cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The
      estimated 10-year survival rate was 68%, the progression-free survival rate was
      67%, and the event-free survival rate was 51%. In multivariate analysis, age >=
      60 years, hemoglobin <10 g/dL, bone marrow basophils >= 5%, any peripheral
      blasts, and clonal evolution were independent adverse factors for survival. The
      estimated 7-year survival rate according to the presence of no factors (n = 154),
      1 or 2 factors (n = 190), or >= 3 factors (n = 24) were 93%, 70%, and 25%,
      respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic
      response at 12 months was associated with significantly better 10-year survival
      rate in a landmark analysis (10-year survival rate, 80%-90%) compared with
      achieving a minor cytogenetic response or a complete hematologic response (10
      year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In
      a landmark analysis that included imatinib response at 12 months, achieving a
      major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving
      a complete hematologic response or a minor cytogenetic response (hazard ratio,
      0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The
      current results indicated that the estimated 10-year survival rate of 68% for
      patients with chronic myeloid leukemia who receive imatinib after failure on
      interferon has improved.

PMID- 22370905
TI  - Adherence to active play and electronic media guidelines in preschool children:
      gender and parental education considerations.
AB  - The primary purpose of the present study was to examine adherence to current
      active play and electronic media use guidelines in a sample of US preschool-aged
      children and to examine whether differences occurred across gender and parental
      education. 164 parents completed an on-line survey to estimate preschool
      children's active play and sedentary behaviors. For weekdays, 50% of the sample
      met the active play guideline with this increasing to 65% during the weekend.
      With respect to electronic media use, 90% of the sample met guidelines during the
      week, with the percentage meeting guidelines dropping to 78% during the weekend.
      A greater percentage of preschool children from high parental education families
      (83.4 +/- 3.3) met electronic media use guidelines on the weekends, compared to
      preschool children from low parental education families (59.4 +/- 8.1) (p =
      0.002). Our findings indicate that a substantial portion of preschool children
      are not meeting active play guidelines and that adherence to active play and
      electronic media use guidelines may be influenced by parental education.

PMID- 22370906
TI  - Mycoplasmal panencephalitis: a neuropathologic documentation.
AB  - Mycoplasmas, particularly Mycoplasma pneumoniae, have been implicated as
      causative agents in a large variety of central nervous system diseases,
      especially acute childhood encephalitis. Postulated pathomechanisms for
      mycoplasma-mediated neurological disease have included: direct infection,
      autoimmunity, and vascular occlusion. Neuropathologic data are meager and are
      reviewed. We report a 3-year-old boy, who developed signs and symptoms of
      encephalitis 7 days after the onset of fever with cough and death 5 days later.
      At autopsy, he displayed diffuse vasogenic edema and perivascular to infiltrative
      inflammatory cells, the latter most prominent in gray matter of brainstem and
      amygdala. The predominant cell was the CD68-positive macrophage, followed by the
      T-lymphocyte. Cells immunolabeled with a polyclonal antibody to M. pneumoniae
      included perivascular to parenchymal macrophages/microglia, occasional
      oligodendrocytes, and neurons, particularly in brainstem. Affected neurons varied
      from morphologically normal to profoundly degenerate and necrotic.
      Ultrastructural study of the inferior olive confirmed the presence of 260-600 nm
      cell-wall-free microorganisms, consistent with mycoplasma, in perivascular cells
      and neurons. Foci of acute disseminated encephalomyelitis also were rarely
      identified. This case report confirms the postulated role of direct infection of
      brain by mycoplasma in acute childhood encephalitis, but also reveals a virus
      like infection of central neurons. The pathogenesis of acute childhood
      encephalitis due to mycoplasma seems to be multifactorial.

PMID- 22370907
TI  - An antibody with high reactivity for disease-associated alpha-synuclein reveals
      extensive brain pathology.
AB  - alpha-Synuclein is the major protein associated with Lewy body dementia,
      Parkinson's disease and multiple system atrophy. Since alpha-synuclein is present
      in the brain in physiological conditions as a presynaptic protein, it is crucial
      to characterize disease-associated modifications to develop an in vivo biomarker.
      With the aim to develop antibodies showing high specificity and sensitivity for
      disease-associated alpha-synuclein, synthetic peptides containing different amino
      acid sequences were used for immunization of mice. After generation of alpha
      synuclein aggregates, ELISA and immunoblotting were used to test the specificity
      of antibodies. Tissue microarray sections originating from different human alpha
      synucleinopathies were used to compare immunostaining with other, commercially
      available antibodies. Immunization of mice with the peptide TKEGVVHGVATVAE (amino
      acid 44-57 of alpha-synuclein) resulted in the generation of a monoclonal
      antibody (5G4), which was able to bind aggregated alpha-synuclein preparation in
      sandwich ELISA or coated on magnetic beads. 5G4 proved to be superior to other
      antibodies in comparative immunohistochemical studies by revealing more
      widespread and distinct alpha-synuclein pathology. Immunoblotting of human brain
      tissue revealed an additional band seen in dementia with Lewy bodies, whereas the
      band representing monomeric alpha-synuclein was very weak or lacking. In summary,
      the 5G4 antibody is most promising for re-evaluation of archival material and may
      offer new perspective for the development of in vivo diagnostic assays for
      detecting disease-associated alpha-synuclein in body fluids.

PMID- 22370908
TI  - Scedosporium apiospermum endopthalmitis treated early with intravitreous
      voriconazole results in recovery of vision.
AB  - AIM: The purpose of this study is to report a case of endogenous endopthalmitis
      caused by Scedosporium apiospermum with a favorable outcome and review previously
      reported cases, their treatment regimens and outcomes. METHODS: An 83-year-old
      man with diabetes mellitus, no other immunocompromising risk factors, and a
      history of S. apiospermum endopthalmitis in the left eye developed endopthalmitis
      in the right eye. Within 72 h of presentation, he was treated with a pars plana
      vitrectomy and intravitreal voriconozole. RESULTS: Vitreous cultures confirmed S.
      apiospermum. The patient responded to treatment, with a favorable outcome and
      full recovery of vision. CONCLUSIONS: Recognition of S. apiospermum
      endopthalmitis and appropriate early intervention with pars plana vitrectomy and
      intravitreal voriconozole can lead to a favorable outcome with restoration of
      visual acuity.

PMID- 22370909
TI  - Ultrafast internal conversion in a low band gap polymer for photovoltaics:
      experimental and theoretical study.
AB  - Ultrafast dynamics upon photoexcitation in a low band gap polymer for
      photovoltaics is investigated both experimentally and theoretically. Our work
      sheds light on the excess energy relaxation processes occurring immediately after
      photon absorption and responsible for dissipation in the photovoltaic process of
      light harvesting and energy storage. A peculiar non-adiabatic decay path through
      a conical intersection (CI) between the higher excited state S(2) and the first
      singlet state S(1) is identified by ultrafast spectroscopy and theoretical
      calculations. Ultrafast twisting of the initially flat conformation in S(2)
      drives the system to the CI connecting the two potential energy surfaces,
      actually eliciting an internal conversion within 60 femtoseconds, followed by
      planarization along the adiabatic surface in S(1). Relaxed potential energy
      profiles (PEPs) of ground and lowest excited states along a dihedral coordinate,
      calculated within the time dependent density functional theory (TDDFT) approach,
      support the S(2)/S(1) CI mechanism. Furthermore a screening of the widely used
      hybrid and range separated exchange-correlation (XC) DFT functionals has been
      carried out finding different descriptions of S(2)/S(1) PEPs and good agreement
      between experimental data and long-range corrected DFT.

PMID- 22370910
TI  - AuAg alloy nanomolecules with 38 metal atoms.
AB  - Au(38-n)Ag(n)(SCH(2)CH(2)Ph)(24) alloy nanomolecules were synthesized, purified
      and characterized by MALDI TOF mass spectrometry. Similar to 25 and unlike 144
      metal atom count AuAg alloy nanomolecules, incorporation of Ag atoms here results
      in loss or smearing out of distinct UV-vis features. We propose that the short
      and long staples contain Au atoms, while the inner core consists of both Au and
      Ag atoms.

PMID- 22370911
TI  - Antithrombotic activity of protein S infused without activated protein C in a
      baboon thrombosis model.
AB  - Protein S (ProS) is an essential plasma protein that enhances the anticoagulant
      activity of activated protein C (APC).  In vitro , purified native human Zn2+
      containing ProS also exerts direct anticoagulant activity by inhibiting
      prothrombinase and extrinsic FXase activities independently of APC. We
      investigated antithrombotic effects of ProS infused without APC in a baboon shunt
      model of thrombogenesis that employs a device consisting of arterial and venous
      shear flow segments. In  in vitro  experiments, the Zn2+-containing human ProS
      used for the studies displayed >10-fold higher prothrombinase inhibitory activity
      and anticoagulant activity in tissue factor-stimulated plasma, and four-fold
      higher inhibition of the intrinsic pathway than the Zn2+-deficient ProS used. In
      the thrombosis model, ProS (33 MUg/minute for 1 hour) or saline was infused
      locally; platelet and fibrin deposition in the shunt were measured over 2 hours.
      During experiments performed at 50 ml/minute blood flow, Zn2+-containing ProS
      inhibited platelet deposition 73-96% in arterial-type flow segments and 90-99% in
      venous-type flow segments; Zn2+-deficient ProS inhibited platelet deposition 52%
      in arterial-type flow segments and 65-73% in venous-type flow segments. At 100
      ml/min blood flow rate, Zn2+-containing ProS inhibited platelet deposition by 39%
      and 73% in the respective segments; Zn2+-deficient ProS inhibited platelet
      deposition by 5% and 0% in the respective segments. Zn2+-containing ProS
      suppressed fibrin deposition by 67-90%. Systemic APC-independent ProS activity
      was significantly increased and thrombin-antithrombin complex levels were
      significantly decreased after infusion of ProS. Thus, infused human Zn2+
      containing ProS is antithrombotic in primates, and may have therapeutic potential
      even in protein C-deficient human patients.

PMID- 22370912
TI  - Gender differences revealed in the right posterior temporal areas during Navon
      letter identification tasks.
AB  - Gender differences in temporo-spectral EEG patterns during verbal cognitive
      performance are poorly understood. The aim of the present study was to examine
      whether the event-related dynamics of EEG differ between genders during the
      performance of Navon letter identification tasks (NLITs). To this end, the EEG
      patterns of 40 subjects were recorded during the NLIT performance. We compared
      behavioral outcomes, event-related temporo-spectral dynamics, and source
      distribution of neural oscillations within cortical regions of male and female
      subjects. We found that male subjects exhibited greater induced neural activities
      than female subjects in right temporo-parietal areas at theta and alpha frequency
      bands. Source imaging for the time ranges at which maximal gender differences
      were observed revealed gender-dependent estimated current densities in the right
      posterior temporal regions. These gender differences can be explained by the
      existence of distinct, gender-specific hemispheric specialization. Thus, gender
      differences should be considered during behavioral tasks and electrophysiological
      measurements.

PMID- 22370913
TI  - A resting-state functional magnetic resonance imaging study on the first-degree
      relatives of persons with schizophrenia.
AB  - In this study, resting state fMRI images and BOLD signals were recorded from 13
      first-degree relatives of schizophrenic patients and 13 healthy controls. The
      data were analyzed with the ReHo approach after realignment, registration, and
      normalization in statistical parametric mapping 2 (SPM2). A two-sample t-test was
      used to analyze the ReHo differences between first-degree relatives and healthy
      controls in a voxel by voxel manner. A combined threshold of p < 0.005 and number
      of voxels >5 was designated as statistically significant. To evaluate cognitive
      deficits in first-degree relatives, attention/vigilance and verbal/visual memory
      were measured. Significant impairments in attention were observed in first-degree
      relatives compared to healthy controls. Significant abnormalities in ReHo were
      observed in resting brain in first-degree relatives. Decreased ReHo was found to
      be distributed over the bilateral middle frontal, middle temporal, cingulate
      gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal
      lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and
      dorsolateral prefrontal cortex. Increased ReHo was found to be distributed in the
      right precuneus and superior temporal gyrus. These changes in ReHo suggest
      abnormality in the resting state brain function of first-degree relatives of
      schizophrenic patients and may be early signs for the development of
      schizophrenia.

PMID- 22370914
TI  - Model to estimate survival in ambulatory patients with hepatocellular carcinoma.
AB  - Survival of patients with hepatocellular carcinoma (HCC) is determined by the
      extent of the tumor and the underlying liver function. We aimed to develop a
      survival model for HCC based on objective parameters including the Model for
      Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is
      based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and
      2008 (derivation cohort) and 904 patients at the Korean National Cancer Center
      between 2000 and 2003 (validation cohort). Multivariate proportional hazards
      models and corresponding risk score were created based on baseline demographic,
      clinical, and tumor characteristics. Internal and external validation of the
      model was performed. Discrimination and calibration of this new model were
      compared against existing models including Barcelona Clinic Liver Cancer (BCLC),
      Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS)
      scores. The majority of the patients had viral hepatitis as the underlying liver
      disease (100% in the derivation cohort and 85% in the validation cohort). The
      survival model incorporated MELD, age, number of tumor nodules, size of the
      largest nodule, vascular invasion, metastasis, serum albumin, and alpha
      fetoprotein. In cross-validation, the coefficients remained largely unchanged
      between iterations. Observed survival in the validation cohort matched closely
      with what was predicted by the model. The concordance (c)-statistic for this
      model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70).
      The score was able to further classify patient survival within each stage of the
      BCLC classification. CONCLUSION: A new model to predict survival of HCC patients
      based on objective parameters provides refined prognostication and supplements
      the BCLC classification.

PMID- 22370915
TI  - Endoscopic full-thickness resection of submucosal gastric tumors.
AB  - BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is a minimally
      invasive method for en bloc resection of gastrointestinal lesions, such as early
      cancer or submucosal tumor. The aim of this pilot study was to evaluate a novel
      EFTR prototype device for full-thickness resection of the gastric wall containing
      artificial submucosal lesions. METHODS: Six artificial submucosal tumors were
      surgically created in the gastric submucosa by implanting 8-mm cork beads in
      anesthetized pigs. EFTR of the lesions was attempted using a prototype device
      which consists of a large transparent plastic cap, loaded onto the tip of the
      endoscope, into which the submucosal lesion and the surrounding gastrointestinal
      wall can be pulled by using suction, a grasping forceps, or a dedicated anchoring
      device. An over-the-scope clip (OTSC) can be deployed underneath the submucosal
      lesion and a pre-loaded snare is used for EFTR above the OTSC. RESULTS: The
      median procedure time was 15 min (interquartile range 11-22). Successful
      resection of the artificial submucosal lesion was achieved in 4/6 (67%) cases.
      Successful EFTR of the gastric wall was achieved in 3/6 (50%) cases. In all
      cases, the OTSC closed the EFTR site completely. CONCLUSIONS: Gastric EFTR using
      the novel EFTR prototype device is feasible in a live animal model. The technique
      can achieve a full-thickness gastric wall and submucosal tumor resection with
      reliable closure of the gastric wall, but further refinements of the technique
      and device are necessary in order to reliably resect submucosal lesions,
      especially larger ones.

PMID- 22370916
TI  - Association of age at diagnosis and ulcerative colitis phenotype.
AB  - BACKGROUND: Ulcerative colitis (UC) primarily affects young adults; however, 12%
      of patients are diagnosed at an advanced age. Previous studies report that older
      patients are less likely to have pancolitis and more likely to have distal
      disease location. AIMS: Our objective was to compare UC phenotype by age of
      diagnosis in a tertiary referral cohort. METHODS: Retrospective database
      analysis. Demographics, disease extent, and EIM were compared by the following
      age of diagnosis groups: <17 years, 17-40 years, and >40 years. RESULTS: A total
      of 260 patients evaluated between July 1, 2004 and April 19, 2010 were included.
      Race, smoking history, extraintestinal manifestations of disease, and disease
      duration were significantly associated with age of diagnosis. As age of diagnosis
      increased, the proportion of non-white patients increased (p = 0.04), former
      smoking history increased (p < 0.001), extraintestinal manifestations of disease
      decreased (p < 0.017), and disease duration decreased (p < 0.0001). As age of
      diagnosis increased, there was a trend for a higher proportion of patients with
      proctitis and a decreased proportion of patients with pancolitis. Multivariable
      analysis adjusting for sex, race, smoking history, family history, and disease
      duration demonstrated that diagnosis at >40 years was associated with a decreased
      likelihood for pancolitis compared to younger cohorts (OR 0.43, 95% CI 0.24,
      0.76). CONCLUSIONS: Diagnosis of ulcerative colitis after age 40 years was
      associated with decreased disease extent compared to younger age groups, even
      after adjustment for sex, race, smoking history, family history, and disease
      duration. Our results suggest that older patients have distinct clinical
      phenotypes.

PMID- 22370917
TI  - The value of thioredoxin family proteins and proliferation markers in dysplastic
      and malignant gallbladders in patients with primary sclerosing cholangitis.
AB  - BACKGROUND AND AIMS: Patients with primary sclerosing cholangitis (PSC) have an
      increased risk for biliary and gallbladder malignancy and markers of early
      malignancy in PSC are lacking. The aims were to evaluate biomarkers to look for
      premalignancy/malignancy. METHODS: All available gallbladder specimens (n = 53)
      in patients with PSC at Karolinska University Hospital between 1985 and 2006 were
      reviewed. Immunohistochemical staining for p53, Ki-67, Cyclin D1 and the
      thioredoxin family redox proteins; Thioredoxin reductase 1 (TrxR1), isoform-TrxR1
      v.2.3.5, Thioredoxin (Trx1) and Glutaredoxin1 (Grx1) was performed on tissues
      from patients with carcinoma (n = 6), dysplasia (n = 7) and non-cancerous
      gallbladder epithelium (n = 6). RESULTS: Dysplasia and carcinoma were found in
      16/53 (30%) cases. Inflammation and fibrosis of the gallbladder wall were more
      common in tissue with gallbladder dysplasia/carcinoma than in benign tissue 12/25
      (48%) versus 4/28 (12%) (p < 0.01) and in 13/21 (62%) versus 3/32 (9%) (p <
      0.0001), respectively. Immunoreactivity for p53, Ki67, Cyclin D1 was detected in
      significantly more cases of dysplasia/carcinoma of the gallbladder than in non
      cancerous epithelium. 2/19 (11%) of the samples were positive in non-cancerous
      epithelium versus 7/17 (41%) in dysplasia/carcinoma (p < 0.05) for TrxR1-v.2.3.5.
      Grx1 was down regulated; more specifically 15/19 (79%) positive cases in non
      cancerous epithelium versus 7/17 (41%) in dysplasia/carcinoma. CONCLUSION: PSC
      patients have a frequency of gallbladder dysplasia/carcinoma of 30% in operative
      specimens. The overexpression of TrxR1-v2,3,5 and down regulation of Grx1 in
      dysplastic gallbladder epithelium suggest that these proteins should be further
      evaluated as possible future immunohistochemical markers in the early diagnosis
      of biliary malignancy in PSC.

PMID- 22370918
TI  - Formulation of a new and simple nonuniform size-modified Poisson-Boltzmann
      description.
AB  - The nonlinear Poisson-Boltzmann equation (PBE) governing biomolecular
      electrostatics neglects ion size and ion correlation effects, and recent research
      activity has focused on accounting for these effects to achieve better physical
      modeling realism. Here, attention is focused on the comparatively simpler
      challenge of addressing ion size effects within a continuum-based solvent
      modeling framework. Prior works by Borukhov et al. (Phys. Rev. Lett. 1997, 79,
      435; Electrochim. Acta 2000, 46, 221) have examined the case of uniform ion size
      in considerable detail. Generalizations to accommodate different species ion
      sizes have been performed by Li (Nonlinearity 2009, 22, 811; SIAM J. Math. Anal.
      2009, 40, 2536) and Zhou et al. (Phys. Rev. E 2011, 84, 021901) using a
      variational principle, Chu et al. (Biophys. J. 2007, 93, 3202) using a lattice
      gas model, and Tresset (Phys. Rev. E 2008, 78, 061506) using a generalized
      Poisson-Fermi distribution. The current work provides an alternative derivation
      using simple statistical mechanics principles that place the ion size effects and
      energy distributions on a consistent statistical footing. The resulting
      expressions differ from the prior nonuniform ion-size developments. However, all
      treatments reduce to the same form in the cases of uniform ion-size and zero ion
      size (the PBE). Because of their importance to molecular modeling and salt
      dependent behavior, expressions for the salt sensitivities and ionic forces are
      also derived using the nonuniform ion size description. Emphasis in this article
      is on formulation and numerically robust evaluation; results are presented for a
      simple sphere and a previously considered DNA structure for comparison and
      validation. More extensive application to biomolecular systems is deferred to a
      subsequent article.

PMID- 22370919
TI  - In vitro neuraminidase inhibitory activities of four neuraminidase inhibitors
      against influenza viruses isolated in the 2010-2011 season in Japan.
AB  - The half maximal inhibitory concentration (IC(50)) of four neuraminidase
      inhibitors (NAIs), oseltamivir, zanamivir, laninamivir, and peramivir; was
      measured using influenza viruses isolated in the 2010-2011 influenza season in
      Japan. Clinical samples for viral isolation were obtained from nasal aspiration,
      nasopharyngeal swab, or self-blown nasal discharge and cultured with Madin-Darby
      canine kidney cells. The type and subtype of H3N2 or B were determined by reverse
      transcriptase polymerase chain reaction (RT-PCR). For the A(H1N1)pdm09 virus, the
      subtype was determined by real-time RT-PCR. IC(50)s to oseltamivir carboxylate,
      zanamivir, laninamivir, and peramivir were determined by a fluorescence-based
      neuraminidase inhibition assay. Influenza viruses were isolated from 269
      patients. A(H1N1)pdm09, H3N2, and B were isolated from 185, 54, and 30 patients,
      respectively. The geometric means of IC(50) for oseltamivir were 0.86 and 0.73 nM
      to A (H1N1) pdm09, except for the two outlier viruses described below and H3N2,
      respectively, and 33.12 nM for B. The geometric means of IC(50) for the other
      three NAIs were lowest to A(H1N1)pdm09 and highest to B. Two A(H1N1)pdm09
      isolates showed very high IC(50) values for oseltamivir (840 and 600 nM) and
      peramivir (19 and 24 nM). No isolate showed significantly high IC(50) values for
      zanamivir or laninamivir. Continuous surveillance against the emergence or spread
      of influenza virus with high IC(50) values for anti-influenza drugs is important.

PMID- 22370920
TI  - Detection of Mycoplasma pneumoniae by loop-mediated isothermal amplification
      (LAMP) assay and serology in pediatric community-acquired pneumonia.
AB  - Rapid diagnosis of Mycoplasma pneumoniae pneumonia is required for treatment with
      effective antimicrobial agents without delay; however, this capacity has not yet
      been established in clinical practice. Recently, a novel nucleic acid
      amplification method termed loop-mediated isothermal amplification (LAMP) has
      been used to rapidly diagnose various infectious diseases. In this study, we
      prospectively evaluated the efficacy of the LAMP assay to rapidly diagnose M.
      pneumoniae pneumonia in clinical practice. Three hundred sixty-eight children
      (median age, 3.8 years; range, 0.1-14.3 years) admitted to our hospital between
      April 2009 and March 2010 for community-acquired pneumonia were enrolled in this
      study. We obtained throat swabs on admission to detect M. pneumoniae DNA and
      paired serum samples on admission and at discharge to assay M. pneumoniae
      antibody titers. M. pneumoniae pneumonia was diagnosed by either a positive LAMP
      assay or a fourfold or greater increase in antibody titer. Overall, 46 children
      (12.5% of the patients with pneumonia) were diagnosed with M. pneumoniae
      pneumonia; of these, 27 (58.7%) were aged less than 6 years. Of the
      aforementioned 46 children, 38 (82.6%) and 37 (80.4%) were identified by LAMP and
      serology, respectively. When the results of serology were taken as the standard,
      the sensitivity and specificity and positive and negative predictive values of
      the LAMP assay were 78.4%, 97.3%, 76.3%, and 97.6%, respectively. We concluded
      the LAMP assay may be useful for rapid diagnosis of M. pneumoniae pneumonia.

PMID- 22370921
TI  - Clinical and microbiological outcomes in treatment of men with non-gonococcal
      urethritis with a 100-mg twice-daily dose regimen of sitafloxacin.
AB  - Several microorganisms cause non-gonococcal urethritis (NGU). Failure to
      eradicate Mycoplasma genitalium from the urethra could be associated with
      persistent or recurrent urethritis; thus, the choice of antibiotics with
      activities potent enough to eradicate M. genitalium is crucial in the treatment
      of NGU. In in vitro studies, sitafloxacin has been shown to be highly active
      against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU,
      including 15 patients with persistent or recurrent NGU and 1 patient with post
      gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to
      assess its efficacy against NGU. We examined first-void urine samples for the
      presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma
      urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and
      44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients,
      who were judged clinically cured. Microorganisms detected before treatment were
      eradicated in 42 (95.5%) patients, who were judged microbiologically cured.
      Regarding microbiological outcomes of specific microorganisms, eradication rates
      of C. trachomatis (n = 33), M. genitalium (n = 11), and U. urealyticum (n = 10)
      were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium
      positive persistent or recurrent NGU who had experienced treatment failures with
      antibiotics, the mycoplasma was eradicated. These results suggested that the
      sitafloxacin regimen used, which was effective on both M. genitalium and C.
      trachomatis infections, could be useful as an appropriate option as first- and
      second-line treatment of NGU.

PMID- 22370922
TI  - Antimicrobial and anti-inflammatory effects of clarithromycin on Mycobacterium
      avium complex replication in cultured human bronchial epithelial cells.
AB  - The Mycobacterium avium complex (MAC) invades cultured human bronchial cells, can
      replicate intracellularly, and facilitates the release of inflammatory cytokines
      and chemokines from cells. The purpose of this study was to examine the effects
      of clarithromycin (CAM) on MAC invasion, replication, and the release of
      cytokines and chemokines. A human bronchial epithelial cell line (BEAS-2B)
      monolayer grown on a tissue culture plate was infected with MAC. After 24 h, the
      cells were washed with Hanks' buffered salt solution, and extracellular bacteria
      were killed. The monolayer was further cultured for 5 days in medium containing
      CAM and subjected to a replication assay. The supernatants were assessed using a
      microchemotaxis assay and enzyme-linked immunosorbent assay (ELISA). mRNA
      expression was evaluated using a DNA array. The amount of intracellular MAC on
      day 5 of culture was significantly lower in the presence of CAM at the levels of
      1* and 4* MIC. CAM inhibited the release of chemotactic activity and the
      production of interleukin (IL)-8 and macrophage chemotactic protein (MCP)-1. DNA
      array analysis of mRNA expression in BEAS-2B cells showed that CAM inhibited the
      expression of inflammatory cytokines and chemokines, involving IL-6, MCP-1, and
      IL-8 mRNA. MAC invaded and replicated in BEAS-2B cells and induced the production
      of chemotactic factors. In contrast, CAM may have bactericidal and bacteriostatic
      effects leading to the inhibition of inflammatory events.

PMID- 22370923
TI  - Association between change in employment status and new-onset depressive symptoms
      in South Korea - a gender analysis.
AB  - OBJECTIVES: This study aimed to investigate the association of change in
      employment status with new-onset depressive symptoms, particularly differences
      stemming from workers' gender, in South Korea. METHODS: We analyzed data from the
      ongoing Korean Welfare Panel Study. After excluding participants who had
      depressive symptoms at baseline (2007), we analyzed 2891 participants who became
      a precarious or permanent worker or unemployed at follow-up (2008) among waged
      workers who were permanent or precarious workers at baseline. Workers were
      classified as permanent workers if they had full-time, secure jobs and were
      directly hired by their employers; workers not meeting all these criteria were
      classified as precarious workers. Depressive symptoms were assessed annually
      using the 11-item Center for Epidemiologic Studies Depression Scale. To reduce
      potential bias due to pre-existing health conditions, we also examined the
      association in a subpopulation excluding participants with any pre-existing
      chronic disease or disability. RESULTS: Compared to those who maintained
      permanent employment, workers who became unemployed following precarious
      employment had higher odds of developing depressive symptoms [odds ratio (OR)
      2.30, 95% confidence interval (95% CI) 1.01-5.25]. In gender-stratified analyses,
      new-onset depressive symptoms were strongly associated with the change from
      precarious to permanent employment (OR 2.57, 95% CI 1.20-5.52) as well as the
      change from permanent to precarious employment (OR 2.88, 95% CI 1.24-6.66) among
      females; no significant association was observed in the male subpopulation.
      CONCLUSIONS: This study found that changes from precarious to permanent work or
      from permanent to precarious work were associated with new-onset depressive
      symptoms among South Korean women.

PMID- 22370924
TI  - Subacute steroid-induced paraparesis: surgical treatment of a devastating
      "invisible" side effect.
AB  - PURPOSE: To emphasize an underestimated side effect following long-term use of
      steroids. METHODS: We report on surgical treatment of two patients with serious
      neurologic deficits caused by epidural spinal lipoma following long-term intake
      of cortisone. RESULTS: Early decompression of the spinal cord by removal of
      epidural lipoma was the most effective treatment in these patients with
      progressive symptoms. CONCLUSION: Diagnostic work-up of such patients should
      include early spinal MRI resulting in surgical intervention, if indicated.
      Decompression of the spinal cord eventually combined with fusion is necessary.

PMID- 22370925
TI  - Less invasive approach to degenerative lumbar deformity surgery.

PMID- 22370926
TI  - Influence of lumbar kyphosis and back muscle strength on the symptoms of
      gastroesophageal reflux disease in middle-aged and elderly people.
AB  - OBJECTIVE: The objectives of this study was to clarify the relationship between
      kyphosis and gastroesophageal reflux disease (GERD) by evaluation of spinal
      alignment, obesity, osteoporosis, back muscle strength, intake of oral drugs, and
      smoking and alcohol history in screening of a community population to determine
      the factors related to GERD symptoms. GERD increases with age and is estimated to
      occur in about 30% of people. Risk factors for GERD include aging, male gender,
      obesity, oral medicines, smoking, and alcohol intake. It has also been suggested
      that kyphosis may influence the frequency of GERD, but the relationship between
      kyphosis and GERD is unclear. SUBJECTS AND METHODS: We examined 245 subjects (100
      males and 145 females; average age 66.7 years old) in a health checkup that
      included evaluation of sagittal balance and spinal mobility with SpinalMouse,
      GERD symptoms using the Frequency Scale for Symptoms of GERD (FSSG)
      questionnaire, body mass index, osteoporosis, back muscle strength, number of
      oral drugs taken per day, intake of nonsteroidal anti-inflammatory drugs
      (NSAIDs), intake of bisphosphonates, and smoking and alcohol intake. RESULTS:
      Multivariate logistic regression analysis including all the variables showed that
      lumbar lordosis angle, sagittal balance, number of oral drugs taken per day, and
      back muscle strength had significant effects on the presence of GERD (OR, 1.10,
      1.11, 1.09 and 1.03; 95% CI, 1.03-1.17, 1.02-1.20, 1.01-1.18 and 1.01-1.04; p =
      0.003, 0.015, 0.031 and 0.038, respectively). The other factors showed no
      association with GERD. CONCLUSION: This study is the first to show that lumbar
      kyphosis, poor sagittal balance; increased number of oral drugs taken per day,
      and decreased back muscle strength are important risk factors for the development
      of GERD symptoms. Thus, orthopedic surgeons and physicians should pay attention
      to GERD in elderly patients with spinal deformity.

PMID- 22370927
TI  - Electric field-controlled directed migration of neural progenitor cells in 2D and
      3D environments.
AB  - Endogenous electric fields (EFs) occur naturally in vivo and play a critical role
      during tissue/organ development and regeneration, including that of the central
      nervous system(1,2). These endogenous EFs are generated by cellular regulation of
      ionic transport combined with the electrical resistance of cells and tissues. It
      has been reported that applied EF treatment can promote functional repair of
      spinal cord injuries in animals and humans(3,4). In particular, EF-directed cell
      migration has been demonstrated in a wide variety of cell types(5,6), including
      neural progenitor cells (NPCs)(7,8). Application of direct current (DC) EFs is
      not a commonly available technique in most laboratories. We have described
      detailed protocols for the application of DC EFs to cell and tissue cultures
      previously(5,11). Here we present a video demonstration of standard methods based
      on a calculated field strength to set up 2D and 3D environments for NPCs, and to
      investigate cellular responses to EF stimulation in both single cell growth
      conditions in 2D, and the organotypic spinal cord slice in 3D. The spinal
      cordslice is an ideal recipient tissue for studying NPC ex vivo behaviours, post
      transplantation, because the cytoarchitectonic tissue organization is well
      preserved within these cultures(9,10). Additionally, this ex vivo model also
      allows procedures that are not technically feasible to track cells in vivo using
      time-lapse recording at the single cell level. It is critically essential to
      evaluate cell behaviours in not only a 2D environment, but also in a 3D
      organotypic condition which mimicks the in vivo environment. This system will
      allow high-resolution imaging using cover glass-based dishes in tissue or organ
      culture with 3D tracking of single cell migration in vitro and ex vivo and can be
      an intermediate step before moving onto in vivo paradigms.

PMID- 22370928
TI  - Association between Ser311Cys  polymorphism in the dopamine D2 receptor gene and
      schizophrenia risk: a  meta-analysis in Asian populations.
AB  - Numerous  studies have evaluated the association between Ser311Cys (rs1801028,
      C>G)  polymorphism of the dopamine D2 receptor (DRD2) gene and schizophrenia
      risk.  However, the specific association is still controversial. We examined
      whether  DRD2 Ser311Cys polymorphism confers schizophrenia risk in Asian
      populations.  Sixteen studies were retrieved reporting on a total of 2268
      schizophrenia  patients and 2423 healthy controls. Meta-analysis of the results
      showed  significant associations between Ser311Cys polymorphism and schizophrenia
      risk  in the comparisons of G versus C (odds ratio (OR) = 1.47, 95% confidence 
      interval (CI) = 1.18-1.83, P = 0.0006) and CG+GG versus CC (OR = 1.45, 95%CI = 
      1.16- 1.82, P = 0.001). In a subgroup analysis by nationality, we found a 
      significant association between Ser311Cys polymorphism and schizophrenia risk  in
      the comparisons of G versus C and CG+GG versus CC genotype in the Japanese 
      population (OR = 1.75, 95%CI = 1.30-2.35, P = 0.0002; OR = 1.72, 95%CI =  1.27
      2.33, P = 0.0004; respectively) but not in Chinese and Indian populations.  In
      conclusion, the G allele of DRD2 Ser311Cys polymorphism involves a potential 
      risk factor for schizophrenia in Asian populations, especially in the Japanese 
      population.

PMID- 22370929
TI  - Genetic analysis of body weights of individually fed  beef bulls in South Africa
      using random regression models.
AB  - The aim of this study was to estimate genetic  parameters for body weights of
      individually fed beef bulls measured at  centralized testing stations in South
      Africa using random regression models.  Weekly body weights of Bonsmara bulls (N
      = 2919) tested between 1999 and 2003  were available for the analyses. The model
      included a fixed regression of the  body weights on fourth-order orthogonal
      Legendre polynomials of the actual days  on test (7, 14, 21, 28, 35, 42, 49, 56,
      63, 70, 77, and 84) for starting age  and contemporary group effects. Random
      regressions on fourth-order orthogonal  Legendre polynomials of the actual days
      on test were included for additive  genetic effects and additional uncorrelated
      random effects of the  weaning-herd-year and the permanent environment of the
      animal. Residual effects  were assumed to be independently distributed with
      heterogeneous variance for  each test day. Variance ratios for additive genetic,
      permanent environment and  weaning-herd-year for weekly body weights at different
      test days ranged from  0.26 to 0.29, 0.37 to 0.44 and 0.26 to 0.34, respectively.
      The  weaning-herd-year was found to have a significant effect on the variation of
      body weights of bulls despite a 28-day adjustment period. Genetic correlations 
      amongst body weights at different test days were high, ranging from 0.89 to 
      1.00. Heritability estimates were comparable to literature using multivariate 
      models. Therefore, random regression model could be applied in the genetic 
      evaluation of body weight of individually fed beef bulls in South Africa.

PMID- 22370930
TI  - Identification of actinomycete  communities in Antarctic soil from Barrientos
      Island using PCR-denaturing  gradient gel electrophoresis.
AB  - The  diversity of specific bacteria taxa, such as the actinomycetes, has not been
      reported from the Antarctic island of Barrientos. The diversity of 
      actinomycetes was estimated with two different strategies that use  PCR
      denaturing gradient gel electrophoresis. First, a PCR was applied, using a  group
      specific primer that allows selective amplification of actinomycete  sequences.
      Second, a nested-PCR approach was used that allows the estimation of  the
      relative abundance of actinomycetes within the bacterial community.  Molecular
      identification, which was based on 16S rDNA sequence analysis,  revealed eight
      genera of actinomycetes, Actinobacterium, Actinomyces,  an uncultured
      Actinomycete, Streptomyces, Leifsonia, Frankineae, Rhodococcus, and
      Mycobacterium. The uncultured Actinomyces sp  and Rhodococcus sp appear to be the
      prominent genera of actinomycetes in  Barrientos Island soil. PCR-denaturing
      gradient gel electrophoresis patterns  were used to look for correlations between
      actinomycete abundance and  environmental characteristics, such as type of
      rookery and vegetation. There  was a significant positive correlation between
      type of rookery and abundance of  actinomycetes; soil samples collected from
      active chinstrap penguin rookeries  had the highest actinomycete abundance.
      Vegetation type, such as moss, which  could provide a microhabitat for bacteria,
      did not correlate significantly with  actinomycete abundance.

PMID- 22370931
TI  - Genetic relationship of cowpea (Vigna unguiculata)  varieties from Senegal based
      on SSR markers.
AB  - Genetic diversity and phylogenetic relationships among  22 local cowpea (Vigna
      unguiculata) varieties and inbred lines collected  throughout Senegal were
      evaluated using simple sequence repeat molecular  markers. A set of 49 primer
      combinations were developed from cowpea  genomic/expressed sequence tags and
      evaluated for their ability to detect  polymorphisms among the various cowpea
      genotypes. Forty-four primer  combinations detected polymorphisms, with the
      remaining five primer sets  failing to yield PCR amplification products. From one
      to 16 alleles were found  among the informative primer combinations; their
      frequencies ranged from 0.60  to 0.95 (mean = 0.79). The genetic diversity of the
      sample varied from 0.08 to  0.42 (mean = 0.28). The polymorphic information
      content ranged from 0.08 to  0.33 (mean = 0.23). The local varieties clustered in
      the same group, except  53-3, 58-53, and 58-57; while Ndoute yellow pods, Ndoute
      violet pods and Baye  Ngagne were in the second group. The photosensitive
      varieties (Ndoute yellow  pods and Ndoute violet pods) were closely clustered in
      the second group and so  were inbred line Mouride and local cultivar 58-57, which
      is also one of the  parents for inbred line Mouride. These molecular markers
      could be used for  selection and identification of elite varieties for cowpea
      improvement and  germplasm management in Senegal.

PMID- 22370932
TI  - (Co)variance components and genetic  parameters for growth traits in Arabi sheep
      using  different animal models.
AB  - The  objective of the present study was to estimate genetic parameters for body 
      weight at different ages in Arabi sheep using data collected from 1999 to 2009. 
      Investigated traits consisted of birth weight (N = 2776), weaning weight (N = 
      2002) and weight at six months of age (N = 1885). The data were analyzed using 
      restricted maximum likelihood analysis, by fitting univariate and multivariate 
      animal models. All three weight traits were significantly influenced by birth 
      year, sex and birth type. Age of dam only significantly affected birth weight. 
      Log-likelihood ratio tests were conducted to determine the most suitable model 
      for each growth trait in univariate analyses. Direct and total heritability 
      estimates for birth weight, weaning weight and weight at six months of age 
      (based on the best model) were 0.42 and 0.16 (model 4), 0.38 and 0.13 (model 4) 
      and 0.14 and 0.14 (model 1), respectively. Estimation of maternal heritability 
      for birth weight and weaning weight was 0.22 and 0.18, respectively. Genetic  and
      phenotypic correlations among these traits were positive. Phenotypic correlations
      among traits were low to moderate. Genetic correlations among traits were 
      positive and higher than the corresponding phenotypic correlations. Weaning 
      weight had a strong and significant correlation with weight at six months of  age
      (0.99). We conclude that selection can be made in animals based on weaning 
      weight instead of the present practice of selection based on weight at six 
      months.

PMID- 22370933
TI  - Philadelphia-negative chromosomal evolution during  treatment for chronic myeloid
      leukemia.
AB  - Chromosome evolution is one of the major mechanisms of  disease progression and
      resistance in chronic myeloid leukemia (CML) patients.  However, the clinical
      significance of chromosomal evolution in the Philadelphia  (Ph)-negative clone
      during therapy is not fully understood. We evaluated 94 CML  patients in the
      chronic phase of CML during treatment of the disease. Six of  them had Ph
      negative chromosome abnormalities during treatment. Four patients  with a single
      abnormality and a good molecular response showed no obvious  complications from
      the chromosomal changes, while two other patients who had  complex abnormalities
      and previous treatment had poor outcomes. Our results  highlight the need for
      close monitoring of this kind of patient, not only on a  molecular level but also
      at the cytogenetic level.

PMID- 22370934
TI  - Molecular characterization of the Andean blackberry, Rubus  glaucus, using SSR
      markers.
AB  - The species Rubus glaucus, also known as the  Andean or "Castilla" blackberry, is
      one of nine edible species of this genus  that grow naturally in Central and
      South America. In Colombia, this species is  the most important of all Rubus
      species for agricultural and commercial  purposes. We used 20 SSRs developed for
      other Rubus species to  characterize 44 Colombian R. glaucus genotypes, collected
      from eight  different departments, and to look for molecular differences between
      thornless  and thorny cultivated blackberries. Eighty-two bands were obtained
      from 28  loci. The genotypes were classified into eight populations,
      corresponding to  collection sites. The mean number of polymorphic alleles per
      locus in all  populations and genotypes ranged from 1.857 to 2.393. Samples
      collected from  Valle del Cauca, Quindio, Caldas, and Risaralda departments had
      the highest  heterozygosity values. The finding of exclusive bands from R.
      glaucus genotypes  from Valle del Cauca, Quindio, and Caldas demonstrates genetic
      and molecular  differentiation between thorny and thornless Andean blackberries.

PMID- 22370935
TI  - Variation in DNA repair gene XRCC3 affects  susceptibility to astrocytomas and
      glioblastomas.
AB  - The gene XRCC3 (X-ray cross complementing group 3) has  the task of repairing
      damage that occurs when there is recombination between  homologous chromosomes.
      Repair of recombination between homologous chromosomes  plays an important role
      in maintaining genome integrity, although it is known  that double-strand breaks
      are the main inducers of chromosomal aberrations.  Changes in the XRCC3 protein
      lead to an increase in errors in chromosome  segregation due to defects in
      centrosomes, resulting in aneuploidy and other  chromosomal aberrations, such as
      small increases in telomeres. We examined  XRCC3 Thr241Met polymorphism using PCR
      RFLP in 80 astrocytoma and glioblastoma  samples. The individuals of the control
      group (N = 100) were selected from the  general population of the Sao Paulo
      State. Odds ratio and 95%CI were calculated  using a logistic regression model.
      Patients who had the allele Met of the XRCC3  Thr241Met polymorphism had a
      significantly increased risk of tumor development  (odds ratio = 3.13; 95%
      confidence interval = 1.50-6.50). There were no  significant differences in
      overall survival of patients. We suggest that XRCC3  Thr241Met polymorphism is
      involved in susceptibility for developing  astrocytomas and glioblastomas.

PMID- 22370936
TI  - Genetic variants on 17q21 are associated with asthma  in a Han Chinese
      population.
AB  - A genome-wide study has shown an association between  SNPs located on 17q21 and
      asthma. Such associations have been identified in  several populations, but
      little is known about the Han Chinese population. We  conducted a case-control
      study in a Han Chinese population to investigate the  relationship between SNPs
      located on 17q21 and asthma; 241 asthmatic patients  and 212 healthy controls
      were recruited from the outpatient clinics of the  Nanfang Hospital, Guangdong
      Province, southern China. We genotyped six SNPs  (rs8067378, rs8069176,
      rs2305480, rs4795400, rs12603332, and rs11650680)  located on 17q21 with the
      Sequenom MassARRAY iPLEX platform. For two of these  six loci (rs2305480 and
      rs8067378), there was evidence of association with  asthma, and there was a weak
      association of asthma with rs8069176. We confirm  that genetic variants on 17q21
      are associated with asthma in the Han Chinese  population.

PMID- 22370937
TI  - Simple and rapid protocol for  the isolation of PCR-amplifiable DNA from
      medicinal plants.
AB  - Medicinal  plant species has a valuable economic importance because of its usage
      as  pharmaceuticals, nutritional, as well as its use in popular medication. For 
      DNA-based techniques, nanogram quantities of the purified DNA are requisite to 
      amplify and yield sufficient amounts of PCR products. SDS-based DNA isolation 
      method was used to extract DNA from 11 species of different aromatic and 
      medicinal plants collected from Saudi Arabia. Three hundred milligrams of fresh 
      shredded plant material was necessary. The DNA purity was further confirmed by 
      agarose gel, restriction endonuclease digestion and microsatellite  primed
      polymerase chain reaction (MP-PCR). DNA yields ranged from 10-20 MUg (in 100-MUL
      elution volumes) from all plant  material evaluated. The DNA obtained was free of
      any contaminating proteins,  polysaccharides and colored pigments. The extracted
      genomic DNA was found  suitable for restriction digestion and PCR amplification.
      Our experimental  procedure provides an easy, suitable, non-toxic, cheap, and
      quick process for  the amplification of DNA from medical plant tissue.

PMID- 22370938
TI  - Position effect variegation  and epigenetic modification of a transgene in a pig
      model.
AB  - Sequences  proximal to transgene integration sites are able to regulate transgene
      expression, resulting in complex position effect variegation. Position effect 
      variegation can cause differences in epigenetic modifications, such as DNA 
      methylation and histone acetylation. However, it is not known which factor, 
      position effect or epigenetic modification, plays a more important role in the 
      regulation of transgene expression. We analyzed transgene expression patterns 
      and epigenetic modifications of transgenic pigs expressing green fluorescent 
      protein, driven by the cytomegalovirus (CMV) promoter. DNA hypermethylation and 
      loss of acetylation of specific histone H3 and H4 lysines, except H4K16 
      acetylation in the CMV promoter, were consistent with a low level of transgene 
      expression. Moreover, the degree of DNA methylation and histone H3/H4 
      acetylation in the promoter region depended on the integration site; 
      consequently, position effect variegation caused variations in epigenetic 
      modifications. The transgenic pig fibroblast cell lines were treated with DNA 
      methyltransferase inhibitor 5-Aza-2'-deoxycytidine and/or histone deacetylase 
      inhibitor trichostatin A. Transgene expression was promoted by reversing the  DNA
      hypermethylation and histone hypoacetylation status. The differences in DNA 
      methylation and histone acetylation in the CMV promoter region in these cell 
      lines were not significant; however, significant differences in transgene 
      expression were detected, demonstrating that variegation of transgene  expression
      is affected by the integration site. We conclude that in this pig  model,
      position effect variegation affects transgene expression.

PMID- 22370939
TI  - Multiple variants of TERT and CLPTM1L constitute risk  factors for lung
      adenocarcinoma.
AB  - Recent studies have shown that 5p15.33 is one of the  chromosomal regions that is
      most consistently altered in lung cancer; common  variants that are located in
      this region have been genotyped in various  populations. However, the genetic
      contribution of these variants to  carcinogenesis is relatively unknown. A clinic
      based case-control study in  Shanghai was undertaken on 196 patients with lung
      cancer and 229 healthy  individuals. TERT rs2736100 and CLPTM1L rs401681 and
      rs402710  were genotyped using the ABI TaqMan Allelic Discrimination assay. For 
      rs2736100, the G variant and the GG genotype were more frequent, whereas the TT 
      genotype was less frequent in patients with lung adenocarcinoma than in 
      controls. The CT genotype at rs401681 was more common and the TT genotype was 
      rare in patients, and the differences were significant between lung 
      adenocarcinoma patients and controls. This was also true for rs402710.  Moreover,
      the frequency of the GGCTCT haplotype was higher and the TTTTTT  frequency was
      lower in patients, especially those with lung adenocarcinoma.  Aberrant linkage
      disequilibrium among the three SNPs was found in patients with  lung
      adenocarcinoma. We conclude that multiple variants at 5p15.33 contribute  to
      susceptibility to lung adenocarcinoma.

PMID- 22370940
TI  - Characterization of nine novel microsatellite loci for  the Venus clam (Cyclina
      sinensis).
AB  - The Venus clam, Cyclina sinensis, is one of the  most important bivalves in China
      marine aquaculture. Using (CA)(15)-enriched  genomic libraries of this species,
      nine novel polymorphic microsatellite loci  were isolated and characterized. The
      mean number of observed alleles per locus  was 16 (range 8-24). The observed and
      expected heterozygosity ranged from 0.119  to 0.872 and from 0.626 to 0.931,
      respectively. Three loci had significant  departure from Hardy-Weinberg
      equilibrium and non-significant linkage  disequilibrium was found among all nine
      loci. These highly informative  microsatellite markers should be useful for
      population genetic analyses of C.  sinensis.

PMID- 22370941
TI  - Characterization of Fusarium species section Liseola by restriction analysis of
      the IGS region.
AB  - Fusarium species section Liseola namely F. fujikuroi, F. proliferatum, F.
      andiyazi, F. verticillioides, and F. sacchari are  well-known plant pathogens on
      rice, sugarcane and maize. In the present study,  restriction analysis of the
      intergenic spacer regions (IGS) was used to  characterize the five Fusarium
      species isolated from rice, sugarcane and  maize collected from various locations
      in Peninsular Malaysia. From the  analysis, and based on restriction patterns
      generated by the six restriction  enzymes, Bsu151, BsuRI, EcoRI, Hin6I, HinfI, 
      and MspI, 53 haplotypes were recorded among 74 isolates. HinfI  showed the most
      variable restriction patterns (with 11 patterns), while EcoRI  showed only three
      patterns. Although a high level of variation was observed, it  was possible to
      characterize closely related species and isolates from  different species. UPGMA
      cluster analysis showed that the isolates of Fusarium from the same species were
      grouped together regardless of the hosts. We  conclude that restriction analysis
      of the IGS regions can be used to characterize Fusarium species section Liseola
      and to discriminate closely related  species as well as to clarify their
      taxonomic position.

PMID- 22370942
TI  - Estimation of taurindicine  hybridization of American Zebu cattle in Brazil.
AB  - Our  objective was to estimate Bos primigenius taurus introgression in  American
      Zebu cattle. One hundred and four American Zebu (Nellore) cattle were  submitted
      to mtDNA, microsatellite and satellite analysis. Twenty-three alleles  were
      detected in microsatellite analysis, averaging 4.6 +/- 1.82/locus. Variance 
      component comparisons of microsatellite allele sizes allowed the construction  of
      two clusters separating taurus and indicus. No significant  variation was
      observed when indicus and taurus mtDNA were  compared. Three possible genotypes
      of 1711b satellite DNA were identified. All  European animals showed the same
      restriction pattern, suggesting a  Zebu-specific restriction pattern. The
      frequencies of B. primigenius indicus-specific  microsatellite alleles and 1711b
      satellite DNA restriction patterns lead to an  estimate of 14% taurine
      contribution in purebred Nellore.

PMID- 22370943
TI  - A possible role of a cerebral energy gene in alcoholism.
AB  - We examined a possible relationship between genes  responsible for energy
      metabolism of the brain and addictive behavior in an  animal model. We used non
      inbred, Swiss mice exposed to a three-bottle  free-choice model [water, 5% (v/v)
      ethanol, and 10% (v/v) ethanol] over a  16-week period, consisting of four
      phases: acquisition, withdrawal, reexposure,  and quinine-adulteration. The mice
      were then behaviorally classified into three  groups: loss-of-control-drinker
      (preference for ethanol and high levels of  consumption during all phases, N =
      6), heavy-drinker (preference for ethanol  and high levels of consumption during
      acquisition and reduction during  quinine-adulteration, N = 7), and light-drinker
      (preference for water during  all phases, N = 10). Another group only received
      tap water (ethanol-naive  control mice, N = 9). Further analysis using
      quantitative real-time PCR showed  that in mice behaviorally classified as loss
      of-control-drinkers, there was a  significant inverse correlation between
      transcript levels of the Hadh gene  and those of other energy metabolism genes in
      the nucleus of the amygdala,  suggesting that this pathway may contribute to
      ethanol consumption in these  mice. We conclude that cerebral energy metabolism
      is involved with ethanol  addiction, meriting further study.

PMID- 22370944
TI  - Effects of the antipsoriatic  drug dithranol on E2A and caspase-9 gene expression
      in vitro.
AB  - Although  the precise causes of psoriasis remain to be elucidated, psoriasis has
      been  known as a disorder in which factors in the immune system, enzymes and
      other  biochemical substances that regulate skin cell division are functionally 
      imbalanced, thereby resulting in rapid proliferation of keratinocytes and 
      incomplete keratinization. The expression of candidate genes such as E2A and 
      caspase-9, which have been recognized to play a critical role in cellular 
      proliferation/differentiation and apoptosis, is of great interest. They may be 
      therapeutically targeted by the antipsoriatic drug, dithranol. We examined the 
      molecular effects of dithranol on the mRNA and protein expression levels of E2A 
      and caspase-9 in the HaCaT keratinocyte cell line. The HaCaT cells were treated 
      with 0-0.5 MUg/mL  dithranol for 30 min. After dithranol was washed out, the
      HaCaT cells were  cultured for 2 h, and their total cellular RNA and proteins
      were isolated.  Quantitative real-time reverse transcriptase-polymerase chain
      reaction and  Western blot were performed to determine the mRNA and protein
      levels of these  two genes. We found that dithranol treatment in the range of
      0.25-0.5 MUg/mL slightly upregulated the mRNA  expression of E2A and caspase-9
      approximately 1.5- and 1.2-fold, respectively.  However, undetectable change and
      minor downregulation of the protein expression  levels were observed for E2A and
      caspase-9, respectively. Consequently, these  genes appear not to be viable
      therapeutic targets for dithranol.

PMID- 22370945
TI  - Isolation and characterization  of polymorphic microsatellite loci from the
      invasive plant Solidago  canadensis (Asteraceae).
AB  - Solidago  canadensis, a clonal herb originally from North America (common  name:
      Canada goldenrod), is an invasive species in many countries. We developed 
      microsatellite primers for this species. Eleven polymorphic loci were generated 
      and primers were designed. Polymorphism of these 11 loci was assessed in 35 
      plants from two populations (Wuhan and Shanghai) in China. The number of  alleles
      per locus ranged from 3 to 14. The observed and expected heterozygosities  varied
      from 0.0732 to 0.7391 and from 0.1177 to 0.8687, respectively. These 
      microsatellite markers will be useful tools for studies of population genetics 
      in the native and invasive range of this species.

PMID- 22370946
TI  - Neutrophil priming by hypoxic preconditioning protects against epithelial barrier
      damage and enteric bacterial translocation in intestinal ischemia/reperfusion.
AB  - Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and
      bacterial translocation (BT). Neutrophil-derived oxidative free radicals have
      been incriminated in the pathogenesis of ischemic injury in various organs, but
      their role in the bacteria-containing intestinal tract is debatable. Primed
      neutrophils are characterized by a faster and higher respiratory burst activity
      associated with more robust bactericidal effects on exposure to a second
      stimulus. Hypoxic preconditioning (HPC) attenuates ischemic injury in brain,
      heart, lung and kidney; no reports were found in the gut. Our aim is to
      investigate whether neutrophil priming by HPC protects against intestinal I/R
      induced barrier damage and bacterial influx. Rats were raised in normoxia (NM) or
      kept in a hypobaric hypoxic chamber (380 Torr) 17 h/day for 3 weeks for HPC,
      followed by sham operation or intestinal I/R. Gut permeability was determined by
      using an ex vivo macromolecular flux assay and an in vivo magnetic resonance
      imaging-based method. Liver and spleen homogenates were plated for bacterial
      culturing. Rats raised in HPC showed diminished levels of BT, and partially
      improved mucosal histopathology and epithelial barrier function compared with the
      NM groups after intestinal I/R. Augmented cytokine-induced neutrophil
      chemoattractant (CINC)-1 and -3 levels and myeloperoxidase activity correlated
      with enhanced infiltration of neutrophils in intestines of HPC-I/R compared with
      NM-I/R rats. HPC alone caused blood neutrophil priming, as shown by elevated
      production of superoxide and hydrogen peroxide on stimulation, increased membrane
      translocation of cytosolic p47(phox) and p67(phox), as well as augmented
      bacterial-killing and phagocytotic activities. Neutrophil depletion reversed the
      mucosal protection by HPC, and aggravated intestinal leakiness and BT following
      I/R. In conclusion, neutrophil priming by HPC protects against I/R-induced BT via
      direct antimicrobial activity by oxidative respiratory bursts and through
      promotion of epithelial barrier integrity for luminal confinement of enteric
      bacteria.

PMID- 22370947
TI  - Comparison of the transient responses of Escherichia coli to a glucose pulse of
      various intensities.
AB  - Dynamic stimulus-responses of Escherichia coli DPD2085, yciG::LuxCDABE reporter
      strain, to glucose pulses of different intensities (0.08, 0.4 and 1 g L(-1)) were
      compared using glucose-limited chemostat cultures at dilution rate close to 0.15
      h(-1). After at least five residence times, the steady-state cultures were
      disturbed by a pulse of glucose, engendering conditions of glucose excess with
      concomitant oxygen limitation. In all conditions, glucose consumption, acetate
      and formate accumulations followed a linear relationship with time. The resulting
      specific uptake and production rates as well as respiratory rates were rapidly
      increased within the first seconds, which revealed a high ability of E. coli
      strain to modulate its metabolism to a new environment. For transition from
      glucose-excess to glucose-limited conditions, the cells rapidly re-established
      its pseudo-steady state. The dynamics of transient responses at the macroscopic
      viewpoint were shown to be independent on the glucose pulse intensity in the
      tested range. On the contrary, the E. coli biosensor yciG::luxCDABE revealed a
      transcriptional induction of yciG gene promoter depending on the quantities of
      the glucose added, through in situ and online monitoring of the bioluminescence
      emitted by the cells. Despite many studies describing the dynamics of the
      transient response of E. coli to glucose perturbations, it is the first time that
      a direct comparison is reported, using the same experimental design (strain,
      medium and experimental set up), to study the impact of the glucose pulse
      intensity on the dynamics of microbial behaviour regarding growth, respiration
      and metabolite productions.

PMID- 22370948
TI  - Oxidation of phenolic compounds by the bifunctional catalase-phenol oxidase
      (CATPO) from Scytalidium thermophilum.
AB  - The thermophilic fungus Scytalidium thermophilum produces a novel bifunctional
      catalase with an additional phenol oxidase activity (CATPO); however, its phenol
      oxidation spectrum is not known. Here, 14 phenolic compounds were selected as
      substrates, among which (+)-catechin, catechol, caffeic acid, and chlorogenic
      acid yielded distinct oxidation products examined by reversed-phase HPLC
      chromatography method. Characterization of the products by LC-ESI/MS and UV-vis
      spectroscopy suggests the formation of dimers of dehydrocatechin type B
      (hydrophilic) and type A (hydrophobic), as well as oligomers, namely, a trimer
      and tetramer from (+)-catechin, the formation of a dimer and oligomer of
      catechol, a dimer from caffeic acid with a caffeicin-like structure, as well as
      trimeric and tetrameric derivatives, and a single major product from chlorogenic
      acid suggested to be a dimer. Based on the results, CATPO oxidizes phenolic
      compounds ranging from simple phenols to polyphenols but all having an ortho
      diphenolic structure in common. The enzyme also appears to have stereoselectivity
      due to the oxidation of (+)-catechin, but not that of epicatechin. It is
      suggested that CATPO may contribute to the antioxidant mechanism of the fungus
      and may be of value for future food and biotechnology applications where such a
      bifunctional activity would be desirable.

PMID- 22370950
TI  - Improving putrescine production by Corynebacterium glutamicum by fine-tuning
      ornithine transcarbamoylase activity using a plasmid addiction system.
AB  - Corynebacterium glutamicum shows a great potential for the production of the
      polyamide monomer putrescine (1,4-diaminobutane). Previously, we constructed the
      putrescine-producing strain PUT1 by deletion of argF, the gene for ornithine
      transcarbamoylase (OTC), and argR, encoding the L-arginine repressor, combined
      with heterologous expression of the Escherichia coli gene for L-ornithine
      decarboxylase SpeC. As a consequence of argF deletion, this strain requires
      supplementation of L-arginine and shows growth-decoupled putrescine production.
      To avoid costly supplementation with L-arginine and the strong feedback
      inhibition of the key enzyme N-acetylglutamate kinase (ArgB) by L-arginine, a
      plasmid addiction system for low-level argF expression was developed. By fine
      tuning argF expression through modifications of the promoter, the translational
      start codon and/or the ribosome binding site, high productivity and titer could
      be obtained. OTC activity varied almost thousandfold between 960 and 1 mU mg-1
      resulting in putrescine yields on glucose from less than 0.001 up to 0.26 g g-1,
      the highest yield in bacteria reported to date. The most promising strain,
      designated PUT21, was characterized comprehensively. PUT21 strain grew with a
      rate of 0.19 h-1 in mineral salt medium without the need for L-arginine
      supplementation and produced putrescine with a yield of 0.16 g g-1 glucose at a
      volumetric productivity of 0.57 g L-1 h-1 and a specific productivity of 0.042 g
      g-1 h-1. The carbon balance suggested that no major unidentified by-product was
      produced. Compared to the first-generation strain PUT1, the putrescine yield
      observed with PUT21 was increased by 60%. In fed-batch cultivation with C.
      glutamicum PUT21, a putrescine titer of 19 g L-1 at a volumetric productivity of
      0.55 g L-1 h-1 and a yield of 0.16 g g-1 glucose could be achieved. Moreover,
      while plasmid segregation of the initial strain required antibiotic selection,
      plasmid segregation in C. glutamicum PUT21 was fully stable for more than 60
      generations without antibiotic selection even in the presence of L-arginine. The
      ornithine decarboxylase gene speC was expressed from this argF addiction plasmid
      ensuring stable putrescine production by the engineered C. glutamicum strain.

PMID- 22370951
TI  - Engineered high content of ricinoleic acid in fission yeast Schizosaccharomyces
      pombe.
AB  - In an effort to produce ricinoleic acid (12-hydroxy-octadeca-cis-9-enoic acid:
      C18:1-OH) as a petrochemical replacement in a variety of industrial processes, we
      introduced Claviceps purpurea oleate ?12-hydroxylase gene (CpFAH12) to
      Schizosaccharomyces pombe, putting it under the control of inducible nmt1
      promoter. Since Fah12p is able to convert oleic acid to ricinoleic acid, we
      thought that S. pombe, in which around 75% of total fatty acid (FA) is oleic
      acid, would accordingly be an ideal microorganism for high production of
      ricinoleic acid. Unfortunately, at the normal growth temperature of 30  degrees
      C, S. pombe cells harboring CpFAH12 grew poorly when the CpFAH12 gene expression
      was induced, perhaps implicating ricinoleic acid as toxic in S. pombe. However,
      in line with a likely thermoinstability of Fah12p, there was almost no growth
      inhibition at 37  degrees C or, by contrast with 30  degrees C and lower
      temperatures, ricinoleic acid accumulation. Accordingly, various optimization
      steps led to a regime with preliminary growth at 37  degrees C followed by a 5
      day incubation at 20  degrees C, and the level of ricinoleic acid reached 137.4
      MUg/ml of culture that corresponded to 52.6% of total FA.

PMID- 22370952
TI  - Volatile sulphur compounds and pathways of L-methionine catabolism in Williopsis
      yeasts.
AB  - Volatile sulphur compounds (VSCs) are important to the food industry due to their
      high potency and presence in many foods. This study assessed for the first time
      VSC production and pathways of L: -methionine catabolism in yeasts from the genus
      Williopsis with a view to understanding VSC formation and their potential flavour
      impact. Five strains of Williopsis saturnus (var. saturnus, var. subsufficiens,
      var. suavolens, var. sargentensis and var. mrakii) were screened for VSC
      production in a synthetic medium supplemented with L: -methionine. A diverse
      range of VSCs were produced including dimethyl disulphide, dimethyl trisulphide,
      3-(methylthio)-1-propanal (methional), 3-(methylthio)-1-propanol (methionol), 3
      (methylthio)-1-propene, 3-(methylthio)-1-propyl acetate, 3-(methylthio)-1
      propanoic acid (methionic acid) and ethyl 3-(methylthio)-1-propanoate, though the
      production of these VSCs varied between yeast strains. W. saturnus var. saturnus
      NCYC22 was selected for further studies due to its relatively high VSC
      production. VSC production was characterised step-wise with yeast strain NCYC22
      in coconut cream at different L: -methionine concentrations (0.00-0.20%) and
      under various inorganic sulphate (0.00-0.20%) and nitrogen (ammonia)
      supplementation (0.00-0.20%), respectively. Optimal VSC production was obtained
      with 0.1% of L: -methionine, while supplementation of sulphate had no significant
      effect. Nitrogen supplementation showed a dramatic inhibitory effect on VSC
      production. Based on the production of VSCs, the study suggests that the Ehrlich
      pathway of L: -methionine catabolism is operative in W. saturnus yeasts and can
      be manipulated by adjusting certain nutrient parameters to control VSC
      production.

PMID- 22370953
TI  - Promotion of glycerol utilization using ethanol and 1-propanol in
      Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe does not grow in media containing
      glycerol as a sole carbon source but uses glycerol in the presence of ethanol.
      Ethanol, but not glycerol, triggered upregulation of gld1+ and fbp1+ during
      glucose starvation even though gld1+ and fbp1+ are essential for growth on
      glycerol. This upregulation occurred at a very low concentration of ethanol. The
      transcriptional regulation of gld1+ was tested in the presence of various
      alcohols, and both ethanol and 1-propanol were found to induce gld1+ and to
      support growth in glycerol-containing media. We suggest that S. pombe has a novel
      ethanol and/or 1-propanol recognition mechanism that upregulates glycerol
      utilization during glucose starvation.

PMID- 22370955
TI  - Understanding fragmentation of prostate cancer survivorship care: implications
      for cost and quality.
AB  - BACKGROUND: Cancer survivors are particularly prone to the effects of a
      fragmented health care delivery system. The implications of fragmented cancer
      care across providers likely include greater spending and worse quality of care.
      For this reason, the authors measured relations between increasing fragmentation
      of cancer care, expenditures, and quality of care among prostate cancer
      survivors. METHODS: A total of 67,736 patients diagnosed with prostate cancer
      between 1992 and 2005 were identified using Surveillance, Epidemiology, and End
      Results (SEER)-Medicare data. Using the Herfindahl-Hirschman Index and a measure
      of the average number of prostate cancer providers over time, patients were
      sorted into 3 fragmentation groups (low, intermediate, and high). The authors
      then examined annual per capita survivorship expenditures and a measure of
      quality (ie, repetitive prostate-specific antigen [PSA] testing within 30 days)
      according to their fragmentation exposure using multinomial logistic regression.
      RESULTS: Patients with highly fragmented cancer care tended to be younger, white,
      and of higher socioeconomic status (all P < .001). Prostate cancer survivorship
      interventions were most common among patients with the highest fragmentation of
      care across providers (P < .001). After adjustment for clinical characteristics
      and prostate cancer survivorship interventions, higher degrees of fragmentation
      continued to be associated with repetitive PSA testing (13.6% for high vs 7.0%
      for low fragmentation; P < .001) and greater spending, particularly among
      patients not treated with androgen deprivation therapy. CONCLUSIONS: Fragmented
      prostate cancer survivorship care is expensive and associated with potentially
      unnecessary services. Efforts to improve care coordination via current policy
      initiatives, electronic medical records, and the implementation of cancer
      survivorship tools may help to decrease fragmentation of care and mitigate
      downstream consequences for prostate cancer survivors.

PMID- 22370956
TI  - Amelioration of renal injury and oxidative stress by the nNOS inhibitor L-VNIO in
      the salt-sensitive mRen2.Lewis congenic rat.
AB  - Salt sensitivity is a key risk factor for cardiovascular disease and renal
      injury. Alterations in renal nitric oxide may contribute to salt-dependent
      increases in blood pressure and tissue damage. Therefore, we assessed the
      expression of nitric oxide synthase (NOS) isoforms in the kidney and the effects
      of nNOS inhibition on renal injury, inflammation, and oxidative stress in the
      female mRen2.Lewis rat (mRen), a model of salt-sensitive hypertension. We find
      that a high-salt diet (4% sodium) significantly reduced endothelial NOS mRNA (2.6
      fold) and protein (1.5-fold) but increased nNOS mRNA (2.4-fold) and protein (1.9
      fold) in the renal cortex of these animals. Immunostaining for nNOS also seemed
      higher in macula densa and cortical tubules of the rats fed a high-salt diet.
      Circulating nitrate and nitrite levels were reduced, including the tissue levels
      of the NOS cofactor tetrahydrobiopterin. Cortical markers of oxidative stress
      (4HNE, 8-OH-deoxyguanosine) and fibrosis were increased; however, mRNA levels of
      the NAD(P)H oxidase components NOX4, p22phox, and p47phox were reduced. Chronic
      treatment with the nNOS inhibitor N-(1-Imino-3-butenyl)-L-ornithine did not
      influence systolic blood pressure after 4 weeks but significantly attenuated
      albuminuria, renal fibrosis, inflammation, and indices of oxidative stress. We
      conclude that an increase in nNOS expression in conjunction with reduced levels
      of cortical tetrahydrobiopterin may stimulate oxidative stress and renal injury
      in the salt-sensitive female mRen2.Lewis rat.

PMID- 22370958
TI  - Aliskiren improves left ventricular dysfunction and reduces cardiac dilation in
      Syrian cardiomyopathic hamsters.
AB  - OBJECTIVE: Chronic activation of the renin-angiotensin-aldosterone system is a
      major contributing factor to the pathogenesis and progression of cardiovascular
      and renal diseases. METHODS: To evaluate the role of renin-angiotensin
      aldosterone system blockade with aliskiren, a direct renin inhibitor, in the
      development and progression of dilated cardiomyopathy in the Syrian
      cardiomyopathic hamster (SCH) model, we treated 1-month-old SCH with aliskiren
      (10 mg.kg.d) over a 4-month period. For comparative purposes, we also evaluated
      the effects of the angiotensin receptor blocker valsartan (10 mg.kg.d) and the
      combination of both drugs. Age-matched golden hamsters were used as controls.
      Left ventricular end-diastolic volume and end-systolic volume, ejection fraction,
      and diastolic function were determined by echocardiography. Systolic blood
      pressure (SBP) was also measured in the left femoral artery by sphygmomanometry.
      RESULTS: Results indicate that at 2 months of age, SBP is higher in SCH than in
      controls, and administration for 1 month of aliskiren, valsartan, or the
      combination of these drugs normalized SBP in SCH to a similar extent. In 5-month
      old SCH, aliskiren improved ejection fraction (from 48.6% +/- 5.8% to 69.4% +/-
      3.2%, n = 5, P < 0.05), left ventricular end-systolic volume (from 0.28 +/- 0.06
      to 0.10 +/- 0.01 mL/100 g body weight), left ventricular end-diastolic volume
      (from 0.61 +/- 0.05 to 0.34 +/- 0.02 mL/100 g body weight), and normalized
      diastolic function (E:A ratio increases from 0.93 +/- 0.13 to 1.70 +/- 0.03, n =
      5, P < 0.05). Similar results were observed with valsartan or the combination of
      aliskiren and valsartan. CONCLUSIONS: Our results indicate that in this animal
      model, aliskiren is as effective as valsartan, or the combination of both drugs,
      in improving diastolic function and in preventing the development of dilated
      cardiomyopathy. These findings suggest that aliskiren may be used as a
      monotherapy in heart failure management. Clinical studies, however, are needed to
      assess the effectiveness of this drug in patients with heart failure.

PMID- 22370957
TI  - Atrial-selective prolongation of refractory period with AVE0118 is due
      principally to inhibition of sodium channel activity.
AB  - The action of AVE0118 to prolong effective refractory period (ERP) in atria but
      not in ventricles is thought to be due to its inhibition of IKur. However, in
      nonremodeled atria, AVE0118 prolongs ERP but not action potential duration (APD70
      90), which can be explained with the inhibition of sodium but not potassium
      channel current. ERP, APD, and the maximum rate of increase of the AP upstroke
      (Vmax) were measured in the canine-isolated coronary-perfused right atrial and in
      superfused ventricular tissue preparations. Whole-cell patch-clamp techniques
      were used to measure sodium channel current in HEK293 cells stably expressing
      SCN5A. AVE0118 (5-10 MUM) prolonged ERP (P < 0.001) but not APD70 and decreased
      Vmax (by 15%, 10 MUM, P < 0.05; n = 10 for each). Ventricular ERP, APD90, and
      Vmax were not changed significantly by 10 MUM AVE0118 (all P = ns; n = 7).
      AVE0118 effectively suppressed acetylcholine-mediated persistent atrial
      fibrillation. AVE0118 (10 MUM) reduced peak current amplitude of SCN5A-WT current
      by 36.5% +/- 6.6% (P < 0.01; n = 7) and shifted half-inactivation voltage (V0.5)
      of the steady-state inactivation curve from -89.9 +/- 0.5 to -96.0 +/- 0.9 mV (P
      < 0.01; n = 7). Our data suggest that AVE0118-induced prolongation of atrial, but
      not ventricular ERP, is due largely to atrial-selective depression of sodium
      channel current, which likely contributes to the effectiveness of AVE0118 to
      suppress atrial fibrillation.

PMID- 22370960
TI  - Revealing the origin of the audiovisual bounce-inducing effect.
AB  - The audiovisual bounce inducing effect (ABE) is a bouncing percept induced by the
      presentation of a sound in a motion display otherwise perceived as streaming. The
      literature suggests that the origin of the ABE is double: the effect stems from
      the action of an attentional component  and that of a non-attentional component.
      However, the type of response classically gathered in ABE studies does not enable
      the disentanglement of the two components. Here, we used the ABE stimuli in a
      detection task and observed the effect of the sound on participants' sensitivity
      (hypothesised  to be linked to the attentional component) and on response bias
      (hypothesised to be linked to the non-attentional component). The sound affected
      sensitivity and response bias in a way that is consistent with that expected by a
      selective modulation of the attentional and non-attentional component  by the
      sound.

PMID- 22370961
TI  - Ventricular tachycardia with frequent retrograde P waves.

PMID- 22370962
TI  - New insights in prevention, diagnosis and treatment of stroke: its relation with
      atrial fibrillation.

PMID- 22370963
TI  - Patterns and time of recurrence after complete resection of esophageal cancer.
AB  - PURPOSE: The results and outcomes of surgical resection for esophageal carcinoma
      have improved remarkably in recent years; however, recurrence still frequently
      develops, even after complete resection. The purpose of this study is to clarify
      the characteristics of recurrence in this patient population. METHODS: Among 208
      patients, who underwent R0 resection for esophageal carcinoma, recurrence
      developed in 61. Clinical data were available for 56 of these patients, who were
      the subjects of this study. We evaluated the time, patterns, and treatment of
      recurrence in these patients. RESULTS: Recurrence developed within 1 and 2 years
      after esophagectomy in 71 and 84% of the patients, respectively, and was
      classified as loco-regional (54%), hematogenous (36%), or mixed type (10%). The
      prognosis of patients with loco-regional recurrence tended to be better than that
      of those with distant metastasis, although the difference was not significant (P
      = 0.088). Patients with recurrence treated by chemotherapy alone or multimodal
      therapy, such as radiation or surgery combined with systemic chemotherapy,
      survived significantly longer than those with untreatable recurrence (P = 0.016).
      CONCLUSION: These findings reinforce the importance of careful follow-up for both
      loco-regional and hematogenous recurrence after esophagectomy, particularly
      during the first 2 years.

PMID- 22370964
TI  - Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor
      lobar lung transplantation: report of a case.
AB  - We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung
      in the presence of newly formed donor-specific antibodies, 10 months after living
      donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the
      unilateral lung. Furthermore, the lung graft was from her husband and HLA
      analysis on the recipient's daughter revealed the same donor-specific HLA
      antigens, which strongly suggested pre-sensitization before lung transplantation.
      Fortunately, we could perform direct crossmatch even 1 year after lung
      transplantation because of the living donors.

PMID- 22370965
TI  - Enabling grand-canonical Monte Carlo: extending the flexibility of GROMACS
      through the GromPy python interface module.
AB  - We report on a python interface to the GROMACS molecular simulation package,
      GromPy (available at https://github.com/GromPy). This application programming
      interface (API) uses the ctypes python module that allows function calls to
      shared libraries, for example, written in C. To the best of our knowledge, this
      is the first reported interface to the GROMACS library that uses direct library
      calls. GromPy can be used for extending the current GROMACS simulation and
      analysis modes. In this work, we demonstrate that the interface enables hybrid
      Monte-Carlo/molecular dynamics (MD) simulations in the grand-canonical ensemble,
      a simulation mode that is currently not implemented in GROMACS. For this
      application, the interplay between GromPy and GROMACS requires only minor
      modifications of the GROMACS source code, not affecting the operation,
      efficiency, and performance of the GROMACS applications. We validate the grand
      canonical application against MD in the canonical ensemble by comparison of
      equations of state. The results of the grand-canonical simulations are in
      complete agreement with MD in the canonical ensemble. The python overhead of the
      grand-canonical scheme is only minimal.

PMID- 22370967
TI  - The steric effect of aromatic pendant groups and electrical bistability in pi
      stacked polymers for memory devices.
AB  - In order to investigate the steric effect of aromatic pendant groups and the
      electrical bistability in nonconjugated polymers potentially for memory device
      applications, two pi-stacked polymers with different steric structures are
      synthesized and characterized. They exhibit two conductivity states and can be
      switched from an initial low-conductivity (OFF) state to a high-conductivity (ON)
      state. Additionally, they demonstrate nonvolatile write-once-read-many-times
      (WORM) memory behavior with an ON/OFF current ratio up to 10(4), and flash memory
      behavior with an ON/OFF current ratio of approximately 10(5). Both steady-state
      and time-resolved fluorescence spectroscopies are used to examine the
      conformational change of the polymers responding to an applied external
      electrical voltage. The results provide useful information on different steric
      effects of pendant groups in polymer chains, resulting in various electrical
      behaviors. The possibility in realizing an "erasable" behavior through breaking
      pi-stacked structures of pendant groups by a reversal of the electric field was
      also discussed on the basis of temperature-dependent fluorescence spectroscopy
      investigation. These results may thus offer a guideline for the design of
      practical polymer memory devices via tuning steric structure of pi-stacked
      polymers.

PMID- 22370966
TI  - Atoh1, an essential transcription factor in neurogenesis and intestinal and inner
      ear development: function, regulation, and context dependency.
AB  - Atoh1 (also known as Math1, Hath1, and Cath1 in mouse, human, and chicken,
      respectively) is a proneural basic helix-loop-helix (bHLH) transcription factor
      that is required in a variety of developmental contexts. Atoh1 is involved in
      differentiation of neurons, secretory cells in the gut, and mechanoreceptors
      including auditory hair cells. Together with the two closely related bHLH genes,
      Neurog1 and NeuroD1, Atoh1 regulates neurosensory development in the ear as well
      as neurogenesis in the cerebellum. Atoh1 activity in the cochlea is both
      necessary and sufficient to drive auditory hair cell differentiation, in keeping
      with its known role as a regulator of various genes that are markers of terminal
      differentiation. Atoh1 is known in other fields as an oncogene and a tumor
      suppressor involved in regulation of cell cycle control and apoptosis. Aberrant
      Atoh1 activity in adult tissue is implicated in cancer progression, specifically
      in medullablastoma and adenomatous polyposis carcinoma. We demonstrate through
      protein sequence comparison that Atoh1 contains conserved phosphorylation sites
      outside the bHLH domain, which may allow regulation through post-translational
      modification. With such diverse roles, tight regulation of Atoh1 at both the
      transcriptional and protein level is essential.

PMID- 22370968
TI  - HIV therapies and the kidney: some good, some not so good?
AB  - Several observational studies have identified tenofovir as an independent risk
      factor for kidney impairment. Conversely, randomized trials have only
      demonstrated minor tenofovir-related changes in kidney function, but these
      studies included patients with normal kidney function and with low underling risk
      for progression of their renal function, had limited size, and limited follow-up.
      Several potential mechanisms of tenofovir nephrotoxicity are known. Atazanavir
      can, equally to indinavir, cause urolithiasis, but both drugs have also been
      associated with chronic kidney disease (CKD) and fast declining eGFR in persons
      without clinical symptoms of urolithiasis, especially when the plasma drug
      concentration is boosted by concomitant ritonavir use. In 2012, only a minority
      of HIV-positive individuals are affected by drug-induced nephrotoxicity. However,
      in the future, the clinical impact and hence the requirement for more research in
      this area will likely increase due to ageing and continued cART exposure of the
      HIV-positive population.

PMID- 22370969
TI  - Aligned carbon nanotubes sandwiched in epitaxial NbC film for enhanced
      superconductivity.
AB  - Highly aligned carbon nanotube (CNT) ribbons were sandwiched in epitaxial
      superconducting NbC films by a chemical solution deposition method. The
      incorporation of aligned long CNTs into NbC film enhances the normal-state
      conductivity and improves the superconducting properties of the assembly.

PMID- 22370971
TI  - Detection of microregional hypoxia in mouse cerebral cortex by two-photon imaging
      of endogenous NADH fluorescence.
AB  - The brain's ability to function at high levels of metabolic demand depends on
      continuous oxygen supply through blood flow and tissue oxygen diffusion. Here we
      present a visualized experimental and methodological protocol to directly
      visualize microregional tissue hypoxia and to infer perivascular oxygen gradients
      in the mouse cortex. It is based on the non-linear relationship between
      nicotinamide adenine dinucleotide (NADH) endogenous fluorescence intensity and
      oxygen partial pressure in the tissue, where observed tissue NADH fluorescence
      abruptly increases at tissue oxygen levels below 10 mmHg(1). We use two-photon
      excitation at 740 nm which allows for concurrent excitation of intrinsic NADH
      tissue fluorescence and blood plasma contrasted with Texas-Red dextran. The
      advantages of this method over existing approaches include the following: it
      takes advantage of an intrinsic tissue signal and can be performed using standard
      two-photon in vivo imaging equipment; it permits continuous monitoring in the
      whole field of view with a depth resolution of ~50 MUm. We demonstrate that brain
      tissue areas furthest from cerebral blood vessels correspond to vulnerable
      watershed areas which are the first to become functionally hypoxic following a
      decline in vascular oxygen supply. This method allows one to image microregional
      cortical oxygenation and is therefore useful for examining the role of inadequate
      or restricted tissue oxygen supply in neurovascular diseases and stroke.

PMID- 22370970
TI  - Impaired cell functions of hepatocytes incubated with plasma of septic patients.
AB  - OBJECTIVE AND DESIGN: The development of liver failure is a major problem in
      septic patients. In this prospective clinical experimental study the
      hepatotoxicity of plasma from septic and non-septic patients was tested. METHODS
      AND SUBJECTS: The basic test components consist of human liver cells (HepG2/C3A)
      used in a standardized microtiter plate assay. After incubation with patient's
      plasma viability of cells (XTT-test), the cytochrome 1A2 activity and synthesis
      of micro albumin were measured. Subjects (28) enrolled comprise the septic shock
      group (SSG, n=10), the non-septic group (NSG, n=5) and the healthy volunteers
      group (HVG, n=13). RESULTS: The 28-day mortality was 30% in the SSG. The APACHE
      II-, SOFA-, and SAPS-scores and the values of bilirubin and prothrombin time as
      INR were significantly higher in the SSG than in the NSG. The cytochrome 1A2
      activity and the release of albumin were significantly reduced in HepG2/C3A cells
      incubated with plasma of the SSG (p<0.05). The cytochrome 1A2 activities were
      higher in survivors compared to non-survivors at the time point 0 and were
      increasing in survivors and decreasing in non-survivors within 54 h in the SSG.
      In the SSG there was a significant decrease in IL-10 and IL-8 between inclusion
      and 54 h. Values of IL-6, TNF alpha and IL-10 were significantly lower in the NSG
      compared with the values of the SSG at inclusion and after 54 h. CONCLUSION: The
      plasma of patients with septic shock impaired cellular functions of HepG2/C3A
      cells.

PMID- 22370973
TI  - GPIIb/IIIa inhibitors: from bench to bedside and back to bench again.
AB  - From the discovery of the platelet glycoprotein (GP) IIb/IIIa and identification
      of its central role in haemostasis, the integrin GPIIb/IIIa (alphaIIbbeta3,
      CD41/CD61) was destined to be an anti-thrombotic target. The subsequent
      successful development of intravenous ligand-mimetic inhibitors occurred during a
      time of limited understanding of integrin physiology. Although efficient
      inhibitors of ligand binding, they also mimic ligand function. In the case of
      GPIIb/IIIa inhibitors, despite strongly inhibiting platelet aggregation,
      paradoxical fibrinogen binding and platelet activation can occur. The quick
      progression to development of small-molecule orally available inhibitors meant
      that this approach inherited many potential flaws, which together with a short
      half-life resulted in an increase in mortality and a halt to the numerous
      pharmaceutical development programs. Limited clinical benefits, together with the
      success of other anti-thrombotic drugs, in particular P2Y12 ADP receptor
      blockers, have also led to a restrictive use of intravenous GPIIb/IIIa
      inhibitors. However, with a greater understanding of this key platelet-specific
      integrin, GPIIb/IIIa remains a potentially attractive target and future drug
      developments will be better informed by the lessons learnt from taking the
      current inhibitors back to the bench. This overview will review the physiology
      behind the inherent problems of a ligand-based integrin inhibitor design and
      discuss novel promising approaches for GPIIb/IIIa inhibition.

PMID- 22370972
TI  - Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory
      solid tumors.
AB  - BACKGROUND: Targeting the cell-surface receptor EphA2, which is highly expressed
      in some solid tumors, is a novel approach for cancer therapy. We aimed to
      evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and
      antitumor activity of MEDI-547, an antibody drug conjugate composed of the
      cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal
      antibody (1C1), in patients with solid tumors relapsed/refractory to standard
      therapy. METHODS: In this phase 1, open-label study with planned dose-escalation
      and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI
      547 (0.08 mg/kg) every 3 weeks. RESULTS: Six patients received 0.08 mg/kg; all
      discontinued treatment. Dose escalation was not pursued. The study was stopped
      before cohort 2 enrollment due to treatment-related bleeding and coagulation
      events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were
      not explored and an MTD could not be selected. The most frequently reported
      treatment-related adverse events (AEs) were increased liver enzymes, decreased
      hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced
      treatment-related serious AEs, including conjunctival hemorrhage, pain (led to
      study drug discontinuation), liver disorder, and hemorrhage. Best response
      included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%).
      Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood.
      Serum MEDI-547 concentrations decreased rapidly, ~70% by 3 days post-dose. No
      accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a
      second dose 3 weeks following dose 1. CONCLUSIONS: The safety profile of MEDI-547
      does not support further clinical investigation in patients with advanced solid
      tumors.

PMID- 22370974
TI  - Hepatocellular carcinoma: detection with diffusion-weighted versus contrast
      enhanced magnetic resonance imaging in pretransplant patients.
AB  - This study evaluates the performance of diffusion-weighted magnetic resonance
      imaging (DWI) for the detection of hepatocellular carcinoma (HCC) in pre-liver
      transplantation patients, compared and combined with contrast-enhanced T1
      weighted imaging (CET1WI), using liver explant as the standard of reference. We
      included 52 patients with cirrhosis (40 men, 12 women; mean age, 56 years) who
      underwent DWI and CET1WI within 90 days of liver transplantation. Magnetic
      resonance images were analyzed for HCC detection in three separate sessions by
      two independent observers: DWI images (DW-set), CET1WI (CE-set), and all images
      together (All-set). Sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), per-patient accuracy, and per-lesion PPV were
      calculated for each image set. A total of 72 HCCs were present in 33 patients at
      explant (mean size, 1.5 cm [range, 0.3-6.2 cm]). Per-patient sensitivity and NPV
      of CE-set were significantly higher than those of DW-set when using pooled data
      between observers (P = 0.02 and 0.03, respectively), whereas specificity, PPV,
      and accuracy were equivalent. Per-lesion sensitivity was significantly higher for
      CE-set versus DW-set (59.0% versus 43.8%; P = 0.008, pooled data from two
      observers). When stratified by lesion size, the difference was significant only
      for lesions with a size between 1 and 2 cm (42.0% for DW-set versus 74.0% for CE
      set; P = 0.001). The addition of DWI to CET1WI improved sensitivity for the more
      experienced observer. CONCLUSION: DWI is outperformed by CET1WI for detection of
      HCC, but represents a reasonable alternative to CET1WI for detection of HCC with
      a size above 2 cm. The addition of DWI to CET1WI slightly increases the detection
      rate.

PMID- 22370976
TI  - [Adjuvant radiotherapy after complete surgical resection in non-small cell lung
      cancer].

PMID- 22370977
TI  - [Recommendation concerning the microscopic classification of lung adenocarcinoma
      presented by International Association for the Study of Lung Cancer, American
      Thoracic Society, and European Respiratory Society].

PMID- 22370978
TI  - [Normal D-dimer concentration in hospitalized patients with lung diseases].
AB  - INTRODUCTION: The use of D-dimer testing is an established part of the diagnosis
      of suspected pulmonary embolism (PE). However, in hospitalized patients many
      various factors might be responsible for increased D-dimer concentration and they
      could lower utility of D-dimer in exclusion of PE in such population. According
      to some published data, calculating the index D-dimer/fibrinogen could increase
      the specificity of D-dimer in the recognition of venous thromboembolism (VTE).
      The aim of the present study was to determine the frequency of normal D-dimer
      concentration in hospitalized patients with lung diseases in whom the
      differential diagnosis of PE is particularly difficult and to evaluate the
      utility of the index D-dimer/fibrinogen in subgroups of patients: with acute VTE
      and with lung cancer. MATERIAL AND METHODS: 619 consecutive patients aged 54.9
      (+/- 15.4) hospitalized in reference pulmonary center were enrolled into
      observation. Among them, there were 96 (15%) patients with acute VTE, 65 (10%)
      with exacerbation of COPD and 172 (27%) with lung cancer. RESULTS: Mean D-dimer
      concentration (Vidas D-dimer New) was 1956 +/- 3691 ng/ml and median value 842
      (45-35 678) ng/ml. Normal D-dimer concentration (< 500 ng/ml) was found in
      225/523 (43%) without acute VTE. In 49% (32/65) patients with COPD and in 25%
      (43/172) patients with lung cancer D-dimer concentration was below 500 ng/ml as
      well. The index D-dimer/fibrinogen was significantly higher in acute VTE patients
      compared to lung cancer patients - 808 +/- 688 and 289 +/- 260 respectively, p <
      0.001. CONCLUSIONS: Normal D-dimer concentration was found in more than 40% of
      patients with lung diseases hospitalized in reference pulmonary center. This
      observation could suggest higher than described in the literature utility of D
      dimer measurement in exclusion of PE in such a population. The value of the index
      D-dimer/fibrinogen, which is significantly higher in acute VTE than in lung
      cancer requires further evaluation to establish its clinical utility.

PMID- 22370979
TI  - [Assessment the efficacy of postoperative radiotherapy in the patients with non
      small cell lung cancer. Retrospective study].
AB  - INTRODUCTION: The basic method of therapy of non-small cell lung cancer is
      surgery. For a number of years a discussion has gone concerning the indications
      for postoperative radiotherapy in the case of non-radical surgical treatment. At
      present, in many centers, the postoperative radiotherapy is recommended for
      patients with confirmed metastases to mediastinal lymph nodes (pN2) and in case
      of microscopic or macroscopic features of incomplete surgical margins. The aim of
      this retrospective study was to assess the results of adjuvant radiotherapy after
      surgical treatment of non-small cell lung cancer. MATERIAL AND METHODS: From
      December 1993 to October 2005 in the Department of Radiotherapy Centre of
      Oncology at Wawelska St. in Warsaw, 366 patients (pts) were radically irradiated
      after surgery. In 192 pts radiotherapy was performed due to incomplete surgical
      margins, in 174 pts - due to metastases to mediastinal lymph nodes - in 26 pts
      both indications coexisted. First and second clinical stage was found in 96 pts:
      (I - 9 pts: 2.4%; II - 87 pts: 24%). Stage IIIA was found in 252 pts (69%) and
      IIIB in 18 pts (5%). Performance status according to Zubrod scale was: 0 - in 302
      pts (82.5%), 1 - in 54 pts (14.8%) and 2 - in 10 pts (2.7%). Retrospective
      analysis of the treatment results was carried out. Survival time and time of
      occurrence of a local progression were assessed. Survival probability was
      calculated with the Kaplan-Meier method. Multidimensional analysis of prognostic
      factors was carried out with the D.R. Cox proportional risk model. RESULTS: In
      the studied group, one year survival was 78.02 +/- 2%, two years, survival was
      54.14 +/- 2%, an five years, survival was 31.03 +/- 2%. The two years, local
      control was estimated as 45.62% +/- 4% and the five years, local control was
      27.37 +/- 4%. Probability of survival was significantly higher in the pts with
      better performance status - median survival in the groups with Zubrod stage 0 and
      1 + 2 were 3.2 and 1.3 years respectively). Patients who received > 50 Gy of
      irradiation had significantly better life expectancy than others - median
      survival in the groups > 50 Gy and <= 50 Gy were 4.42 and 2.25 years
      respectively). Frequency of local recurrence was lower in the group of pts who
      received > 50 Gy of irradiation, than in remaining pts. Local recurrences were
      not observed in the pts treated with 3D radiotherapy regimen, but this group of
      pts received also higher dose of irradiation than others. Multiple survival
      analysis revealed that dose of irradiation <= 50 Gy, worse performance status and
      older age of the patient were independent adverse prognostic indicators.
      CONCLUSIONS: 1. The results of postoperative radiotherapy in his retrospective
      study were strongly influenced by the dose of irradiation, patients' age and
      performance status. Total radiotherapy dose <= 50 Gy, older age of the patients
      and worse performance status (1 + 2) were negative survival indicators. 2. 3D
      technique of irradiation was combined with the best regional control of the
      disease.

PMID- 22370980
TI  - [Measurement of bronchoconstrictive eicosanoids in chronic obstructive pulmonary
      disease].
AB  - INTRODUCTION: The aim of the study was the evaluation of the concentration of
      9alpha11beta prostaglandin F(2) - a stable metabolite of prostaglandin D(2)
      (PGD(2)) and leukotriene E(4) (LTE(4)) in stable and exacerbated COPD patients.
      MATERIAL AND METHODS: 29 COPD patients aged 73 +/- 8.34, mean FEV1 = 48.64 +/-
      15.75% of predictive value and 29 healthy controls aged 57.48 +/- 10.86, mean
      FEV1 = 97.17 +/- 13.81% of predictive value participated in this study. Samples
      of urine and blood were taken from COPD patients during exacerbation and in
      stable state of the disease; LTE(4) was determined in urine using commercial
      enzyme immunoassay (EIA) and 9alpha11beta prostaglandin F(2) (9alpha11betaPGF(2))
      - stable metabolite of PGD(2) was evaluated in blood and urine using GC/MS.
      RESULTS: LTE(4) concentration in urine (677.15 vs. 436.4 pg/mg of creatinine; p =
      0.035) and 9alpha11betaPGF(2) in blood serum (5.35 vs. 3.07 pg/ml; p = 0.007)
      were significantly higher in exacerbated COPD patients than in control group.
      There was no difference in LTE(4) level in urine and 9alpha11betaPGF2 in blood
      serum between exacerbated and stable COPD. The urinary 9alpha11betaPGF(2)
      concentration did not differ between all studied groups. We found a positive
      correlation between smoking history and the urine LTE(4) level (r = 0.395; p =
      0.002) as well as blood 9alpha11betaPGF(2) concentration (r = 0.603; p = 0.001)
      in COPD patients. CONCLUSIONS: 9alpha11betaPGF(2) and LTE(4) level in urine did
      not differ between the stable COPD group and the control group. We also did not
      find any difference between LTE4 level in urine and 9alpha11betaPGF(2) in blood
      and urine between exacerbated and stable COPD. Finally, LTE(4) concentration in
      urine and 9alpha11betaPGF(2) in blood occurred to be significantly higher in
      exacerbated COPD patients than in control group.

PMID- 22370981
TI  - [Virtual bronchoscopy and bronchofiberoscopy--a comparison of diagnostic value in
      assessment of centrally localized lung tumor].
AB  - INTRODUCTION: Virtual bronchoscopy (VB) is a new, noninvasive diagnostic
      technique which allows visualizing trachea and bronchi. Virtual images are
      created on the basis of data derived from helical CT scans using special
      protocol. A reconstructed, virtual image of the bronchial tree is very similar to
      that seen during conventional bronchofiberoscopy (FOB). The aim of the study was
      to compare VB images of the bronchi with those coming from FOB and evaluate
      diagnostic value of VB in centrally localized lung tumor. MATERIAL AND METHODS:
      The studied group consisted of 40 patients with suspicion of centrally localized
      lung cancer. Primary diagnosis was based on the chest X-ray. Each patient
      underwent CT and bronchofiberoscopy and after those routine procedures the VB
      analysis was performed. The results of the FOB were not known for radiologist
      performing VB. In both used methods, FOB and VB, the evaluation and comparison of
      the features of tumor presence, bronchial stenosis and widening of the carina
      were performed. In all 40 patients lung cancer was confirmed. The diagnosis was
      established by histopathologic examination of the tissue biopsy: 32 patients
      (80%)--non small cell lung cancer, 2 patients (5%)--small cell lung cancer, 5
      patients (12.5%)--squamous cell carcinoma, 1 patient (2.5%)--carcinoid. RESULTS:
      Diagnostic value of VB in assessment of the for presence of the tumor in bronchus
      was: sensitivity 79.5%, specificity 95.5%, for bronchial stenosis: sensitivity
      58.6%, specificity 98.1% and for widening of carina: sensitivity 60.7%,
      specificity 97.7%. CONCLUSION: The results indicate that virtual bronchoscopy is
      highly sensitive and specific diagnostic method, a clinically valuable for the
      evaluation of lung tumor with a central location.

PMID- 22370982
TI  - [Chronic obstructive pulmonary disease in women].
AB  - For the past several years the number of women suffering from chronic obstructive
      pulmonary disease (COPD) has been steadily increasing. This fact prompts the
      debate which factors, in addition to considerably increasing prevalence of
      cigarette smoking among young women, are responsible for these epidemiologic
      changes. Differences in the natural history and prognosis of COPD in females and
      males are presented in the paper, as well as the number of potential
      ethiopathogenetic and pathophysiologic factors influencing these variations.
      Among them, differences in the COPD risk factors spectrum in both genders and in
      airways anatomy are pointed out, and the mechanisms responsible for greater
      women's susceptibility to components of cigarette smoke, which reflect genetic
      (enzyme polymorphisms), epigenetic (diminished DNA methylation)  and hormonal
      (estrogens) influences on xenobiotics metabolism. Further, sex-related
      differences regarding COPD phenotypes  (chronic bronchitis vs. emphysema),
      immunological markers and clinical manifestation of disease are underlined in the
      paper. More frequent coexistence of anxiety and depression, COPD exacerbations
      and worse quality of life in women are also emphasized. Other differences,
      pointed out by authors include autoimmunological conception of pathogenesis of
      COPD  (greater female susceptibility to produce autoantibodies), risk factors of
      disease exacerbation and, at last, response to certain forms of COPD treatment
      (nicotine replacement therapy, long-term oxygen therapy).

PMID- 22370983
TI  - [Small airways in obstructive lung diseases].
AB  - The term small airways (SA) applies to the bronchi below 7th generation with
      diameter smaller than 2 mm. This paper presents data showing that this part of
      the respiratory system is distinct in terms of its architecture, physiology and
      pathophysiology.  The most important role SA play in obstructive airway diseases.
      In healthy subjects SA resistance accounts for 10% of the total airway resistance
      while in patients with obstructive disease, due to the constriction of the
      airways together with airway inflammation, SA are responsible even for 60% of the
      total resistance. Changes in SA in asthma and COPD are responsible for air
      trapping especially prominent in the latter disease. There are no precise tools
      to diagnose SA. Depending  availability and experience HRCT, body pletysmography
      (RV/TLS plus other parameters) are frequently used. Some hope for the future is
      placed in combined use of oscilometry, multiple (or single) breath nitrogen wash
      out and eNO concentration measurement.  Due to our increasing knowledge on the
      role of SA in airway obstruction ultra-fine particle aerosols have been developed
      that penetrate to this compartment of the respiratory system (deposition
      confirmed in cascade impactors as well as by ozone  scans after aerosol
      inhalation). Authors present selected publications investigating whereas deep
      drug penetration influences its clinical efficacy. For LABAs deposition in SA
      doesn't seem to increase their bronchodilating effect. Using ultrafine CS aerosol
      allows to maintain clinical effects even with half the dose of the active
      steroid, however. In summary, SA seem to be crucial in obstructive diseases of
      the airways and therefore constitute an important target for therapy.

PMID- 22370984
TI  - [Neurofibromatosis type 1 with interstitial pulmonary lesions diagnosed in adult
      patient. A case study and literature review].
AB  - A case of a 43-year-old man with clinically diagnosed neurofibromatosis type I
      (NF-1, von Recklinghausen disease), was referred to a lung disease unit in order
      to diagnosis of worsening tolerance to physical effort, and aetiology of
      radiological  cystic lesions in the lungs, seen in the high-resolution computed
      tomography (HRCT). Since childhood the patient has been treated for epilepsy, and
      a 3rd degree tricuspid valve incompetence, without pulmonary hypertension was
      detected during right heart catheterization. Finally, the interstitial pulmonary
      lesions were attributed to the primary disease, and it was said they need further
      clinical observation in order to determine their dynamics. The observed
      deterioration in patient's tolerance to physical effort was connected to the
      accompanying infection of the respiratory system with Klebsiella oxytoca and 
      Staphylococcus aureus, with cystic lesions in lungs and tricuspid valve
      incompetence.   The report describes the criteria for NF-1 diagnosis, as well as
      points out the controversies of coexistence of interstitial pulmonary lesions in
      the clinical picture of the disease.

PMID- 22370985
TI  - [Yellow nail syndrome in a patient with membranous glomerulonephritis].
AB  - Yellow nail syndrome (YNS) is a condition characterized by yellow-green
      coloration of nails, respiratory manifestations and lymphoedema. This article
      presents 52-year-old patient with membranous glomerulonephritis, hospitalized at
      the National  Tuberculosis and Lung Diseases Research Institute in Warsaw,
      because of suspected allergic aspergillosis. Based on clinical and radiological
      evaluation the diagnosis of YNS was established. Treatment of renal disease did
      not affect the course of yellow nail syndrome. During the two-year follow-up,
      despite stable renal parameters we observed the progression of respiratory
      manifestations (bronchiectasis, pleural effusions).

PMID- 22370986
TI  - [Changes in classiffication of primary lung adenocarcinoma according to
      reccomendations of International Association for the Study of Lung Cancer/
      /American Thoracic Society/European Respiratory Society].

PMID- 22370987
TI  - [Small biopsies and cytologic specimens management in microscopic diagnosis and
      subtyping of non-small cell lung cancer, as recommended by IASLC/ATS/ERS].

PMID- 22370988
TI  - [Highlights from the ERS Congress in Amsterdam, 24-28 September, 2011].

PMID- 22370989
TI  - [Out of concern for diligence in science--commentary to the paper of T.
      Golczewski "Spirometry--comparison of Lubinski's prediction equations for Polish
      population with ECSC/ERS and Falaschetti's equations"].

PMID- 22370992
TI  - Effects of large doses of arachidonic acid added to docosahexaenoic acid on
      social impairment in individuals with autism spectrum disorders: a double-blind,
      placebo-controlled, randomized trial.
AB  - Autism spectrum disorders are a neurodevelopmental disorders with reduced
      cortical functional connectivity relating to social cognition. Polyunsaturated
      fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) may have key
      role in brain network maturation. In particularly, ARA is important in signal
      transduction related to neuronal maturation. Supplementation with larger ARA
      doses added to DHA may therefore mitigate social impairment. In a 16-week, double
      blind, randomized, placebo-controlled trial, we evaluated the efficacy of
      supplementation with large doses of ARA added to DHA (n = 7) or placebo (n = 6)
      in 13 participants (mean age, 14.6 [SD, 5.9] years). To examine underlying
      mechanisms underlying the effect of our supplementation regimen, we examined
      plasma levels of antioxidants transferrin and superoxide dismutase, which are
      useful markers of signal transduction. The outcome measures were the Social
      Responsiveness Scale and the Aberrant Behavior Checklist-Community. Repeated
      measures analysis of variance revealed that our supplementation regimen
      significantly improved Aberrant Behavior Checklist-Community-measured social
      withdrawal and Social Responsiveness Scale-measured communication. Treatment
      effect sizes were more favorable for the treatment group compared with the
      placebo group (communication: treatment groups, 0.87 vs, placebo, 0.44; social
      withdrawal: treatment groups, 0.88, vs placebo, 0.54). There was a significant
      difference in the change in plasma transferrin levels and a trend toward a
      significant difference in the change in plasma superoxide dismutase levels
      between the 2 groups. This preliminary study suggests that supplementation with
      larger ARA doses added to DHA improves impaired social interaction in individuals
      with autism spectrum disorder by up-regulating signal transduction.

PMID- 22370991
TI  - Androgen resistance in female mice increases susceptibility to DMBA-induced
      mammary tumors.
AB  - Hormones, notably estrogens, are pivotal in the origins of breast cancer but
      androgenic effects, while supported by persistence of AR expression in breast
      cancers, remain controversial. This study determined the role of the androgen
      actions via androgen receptor (AR) in experimental mammary cancer. Androgen
      resistant female and male mice (ARKO) were generated using Cre/loxP technique and
      featured a global AR inactivation. The effect of AR inactivation and influence of
      genetic background on 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis
      was confirmed using two separate ARKO models with different genetic backgrounds.
      The onset of palpable mammary tumors was significantly faster in ARKO females
      (median time 22 vs 34 weeks, respectively; (p = 0.0024; multivariate Cox
      regression) compared to WT and independent of the mouse genetic background. The
      cumulative incidence at 9 months was 81 +/- 10% [mean +/- SE] for ARKO compared
      to 50 +/- 13% in WT females. The increased DMBA susceptibility of ARKO females
      was associated with a higher epithelial proliferation index but not with major
      structural or receptor (estrogen or progesterone) expression differences between
      the virgin WT or ARKO female mammary glands. AR inactivation allowed substantial
      ductal extension in ARKO males while WT males displayed only rudimentary
      epithelial branches or complete regression of epithelial structures. Yet, DMBA
      did not induce epithelial mammary tumors in WT or ARKO males, demonstrating that
      AR inactivation alone is insufficient to promote mammary tumors. These results
      demonstrate that AR inactivation accelerates mammary carcinogenesis in female
      mice exposed to the chemical carcinogen DMBA regardless of mouse genetic
      background but require prior exposure to endogenous ovarian hormones.

PMID- 22370993
TI  - Risk factors associated with metabolic syndrome in bipolar and schizophrenia
      subjects treated with antipsychotics: the role of folate pharmacogenetics.
AB  - Folate has been implicated in cardiovascular disease with atypical antipsychotic
      (AAPs) use, and individuals with methylenetetrahydrofolate reductase (MTHFR) and
      catechol-O-methyl transferase (COMT) variants are at greater risk. This study
      examined the relationship between the MTHFR 677C/T, MTHFR 1298A/C, and COMT
      Val158Met variants; metabolic syndrome; and lifestyle measures in schizophrenia
      and bipolar subjects. A total of 237 subjects with bipolar or schizophrenia
      receiving an antipsychotic for at least 6 months were included in this cross
      sectional analysis. Subjects were screened for the metabolic syndrome (National
      Cholesterol Education Program Adult Treatment Panel III criteria) and MTHFR
      677C/T, MTHFR 1298A/C, and Val158Met genotypes. In addition, serum folate and
      homocysteine were measured along with lifestyle factors. The subject's mean age
      was 44.7 (SD, 11.7) years; 72% were white, and 51% male; 61% were receiving an
      AAP; the mean body mass index was 32.6 (SD, 8.2) kg/m, and 48% were current
      smokers. Overall, 41% met metabolic syndrome criteria (n = 98). There were no
      differences in age, sex, AAP exposure, or body mass index between genotype
      groups. Metabolic syndrome was related to age, smoking, and the MTHFR 677T and
      COMT 158Val alleles (chi = 34.4, P < 0.0001). In addition, AAP use showed a trend
      association with metabolic syndrome (chi = 3.21, P = 0.07). These data support
      our previous reports and add more data pointing to folate's role in mediating a
      link between mental illness and cardiovascular disease. Use of this information
      clinically may help to reduce the risk for AAP metabolic complications in those
      whose clinical care necessitates the use of AAPs.

PMID- 22370994
TI  - QSAR classification of metabolic activation of chemicals into covalently reactive
      species.
AB  - Metabolic activation of chemicals into covalently reactive species might lead to
      toxicological consequences such as tissue necrosis, carcinogenicity,
      teratogenicity, or immune-mediated toxicities. Early prediction of this
      undesirable outcome can help in selecting candidates with increased chance of
      success, thus, reducing attrition at all stages of drug development. The ensemble
      modelling of mixed features was used for the development of a model to classify
      the metabolic activation of chemicals into covalently reactive species. The
      effects of the quality of base classifiers and performance measure for sorting
      were examined. An ensemble model of 13 naive Bayes classifiers was built from a
      diverse set of 1,479 compounds. The ensemble model was validated internally with
      five-fold cross validation and it has achieved sensitivity of 67.4% and
      specificity of 93.4% when tested on the training set. The final ensemble model
      was made available for public use.

PMID- 22370995
TI  - Strengthen forensic entomology in court--the need for data exploration and the
      validation of a generalised additive mixed model.
AB  - Developmental data of juvenile blow flies (Diptera: Calliphoridae) are typically
      used to calculate the age of immature stages found on or around a corpse and thus
      to estimate a minimum post-mortem interval (PMI(min)). However, many of those
      data sets don't take into account that immature blow flies grow in a non-linear
      fashion. Linear models do not supply a sufficient reliability on age estimates
      and may even lead to an erroneous determination of the PMI(min). According to the
      Daubert standard and the need for improvements in forensic science, new statistic
      tools like smoothing methods and mixed models allow the modelling of non-linear
      relationships and expand the field of statistical analyses. The present study
      introduces into the background and application of these statistical techniques by
      analysing a model which describes the development of the forensically important
      blow fly Calliphora vicina at different temperatures. The comparison of three
      statistical methods (linear regression, generalised additive modelling and
      generalised additive mixed modelling) clearly demonstrates that only the latter
      provided regression parameters that reflect the data adequately. We focus
      explicitly on both the exploration of the data--to assure their quality and to
      show the importance of checking it carefully prior to conducting the statistical
      tests--and the validation of the resulting models. Hence, we present a common
      method for evaluating and testing forensic entomological data sets by using for
      the first time generalised additive mixed models.

PMID- 22370996
TI  - Cardiac channelopathy causing sudden death as revealed by molecular autopsy.
AB  - BACKGROUND: Mutations in cardiac ion channel genes have been identified to cause
      sudden unexplained deaths (SUD), and polymorphisms have also been suggested to be
      risk factors. Therefore, postmortem genetic testing has become an important tool
      in elucidating the cause of death. METHODS AND RESULTS: In a sudden death case, a
      LQT-3-associated mutation (Il768V) in the cardiac sodium channel gene SCN5A was
      detected beside the common polymorphism H558R which is known to mitigate the
      effect of mutations in the gene. Both sequence variations were heterozygous.
      Large number of intervening base pairs make it impossible to identify whether
      they were located in cis or trans. Functional consequences of both variants were
      characterized after expressing different cRNAs in Xenopus oocytes by voltage
      clamp measurements. Western blot analysis indicates that the cis configuration of
      both variants may lead to a null allele. Since the woman had received an
      injection of Ultracain(r), the potential effect of this drug was tested. In a
      trans configuration of both variants, the mutant channel exhibited an increase
      susceptibility of at least 10% for blocking with the drug articaine. Another
      novel finding is that the midpoint of activation in the case of the mutant
      channel is leftward shifted of at least -10 mV. CONCLUSION: The results of the
      study suggest that postmortem molecular screening is an important tool to
      elucidate the cause of SUD and that the administration of a drug and a functional
      interaction between polymorphisms and ion channel mutations may trigger the risk
      for sudden death.

PMID- 22370997
TI  - Nasal ciliary motility: a new tool in estimating the time of death.
AB  - Determination of time since death is one of the most difficult and crucial issue
      in forensic medicine. Apart from body cooling, which is commonly used in the
      early postmortem interval (PMI), supravital reactions are the most interesting
      postmortem changes for time of death estimation. Nasal ciliary motility has been
      occasionally observed in postmortem period although no studies have focused on
      this phenomenon for forensic purposes. We aimed to evaluate the diagnostic
      usefulness of ciliary motility as a potential tool in estimating the time of
      death. Specimens of ciliated epithelium from 100 consecutive cadavers were
      obtained by scraping the nasal mucosa at three different postmortem intervals.
      The samples were then smeared on a slide, and an in vitro evaluation of ciliary
      movement was analyzed by phase-contrast microscopy. A postmortem nasal ciliary
      motility was observed, and a statistically significant relationship between
      decreasing ciliary movements and increasing postmortem interval was detected even
      in presence of putrefactive changes of nasal ultrastructure integrity. Some
      peculiar causes of death seem to influence ciliary motility in the early PMI,
      while no significant correlations with sex or age were observed. According to the
      results of this study, postmortem evaluation of nasal ciliary motility may be a
      bona fide and a feasible option for estimating the time of death.

PMID- 22370998
TI  - Minimally invasive decompression of chronic subdural haematomas using hollow
      screws: efficacy and safety in a consecutive series of 320 cases.
AB  - BACKGROUND: Chronic subdural haematoma (cSDH) is a frequent pathology in
      neurosurgery. Surgical treatment varies widely and is often characterised by
      repeated decompression. Therapeutic efficacy was evaluated by clinical symptom
      relief and haematoma reduction on preoperative and postoperative CT scans.
      METHODS: We investigated a consecutive series of 320 cases of cSDH between 2006
      and 2010. In this series, the first- and second-line treatments were performed
      via hollow-screw placement under local anaesthesia, whereas enlarged burr holes
      under general anaesthesia were used as third-line treatment. RESULTS: In general,
      63.3% of cases were sufficiently treated by a single operation, while 16.2%
      needed a second procedure with hollow screws. Only 20.5% needed open surgery by
      an enlarged burr hole with membranectomy under general anaesthesia. After the
      first operation, initial symptoms improved in 80.3% of cases, remained unchanged
      in 15.5% and worsened in 4.2% of cases. Mean age was 74.6 +/- 12.1 years, with
      only one case of severe surgery-related complication. CONCLUSIONS: Initial
      placement of hollow screws under local anaesthesia is a safe and sufficient
      treatment in most cases, and should be favoured as first-line treatment in
      patients with cSDH, since these patients are often of older age and present with
      distinct comorbidity.

PMID- 22370999
TI  - A case of chronic active Epstein-Barr virus infection mimicking adult-onset
      Still's disease.
AB  - An 83-year-old man was diagnosed with adult-onset Still's disease (AOSD) based on
      clinical and laboratory findings. However, glucocorticoid had little effect.
      Epstein-Barr virus (EBV)-DNA was detected in peripheral blood, and autopsy
      findings confirmed a diagnosis of chronic active EBV infection (CAEBV). CAEBV
      mimics AOSD, and the presence of articular involvement and leukocytosis does not
      exclude the possibility of CAEBV. CAEBV should be included in the differential
      diagnosis of AOSD, and measurement of EBV-DNA is essential.

PMID- 22371000
TI  - Erratum to: new drug developments for patients with metastatic soft tissue
      sarcoma.

PMID- 22371001
TI  - An experimental system to study mechanotransduction in fetal lung cells.
AB  - Mechanical forces generated in utero by repetitive breathing-like movements and
      by fluid distension are critical for normal lung development. A key component of
      lung development is the differentiation of alveolar type II epithelial cells, the
      major source of pulmonary surfactant. These cells also participate in fluid
      homeostasis in the alveolar lumen, host defense, and injury repair. In addition,
      distal lung parenchyma cells can be directly exposed to exaggerated stretch
      during mechanical ventilation after birth. However, the precise molecular and
      cellular mechanisms by which lung cells sense mechanical stimuli to influence
      lung development and to promote lung injury are not completely understood. Here,
      we provide a simple and high purity method to isolate type II cells and
      fibroblasts from rodent fetal lungs. Then, we describe an in vitro system, The
      Flexcell Strain Unit, to provide mechanical stimulation to fetal cells,
      simulating mechanical forces in fetal lung development or lung injury. This
      experimental system provides an excellent tool to investigate molecular and
      cellular mechanisms in fetal lung cells exposed to stretch. Using this approach,
      our laboratory has identified several receptors and signaling proteins that
      participate in mechanotransduction in fetal lung development and lung injury.

PMID- 22371002
TI  - Pandemic and seasonal vaccine coverage and effectiveness during the 2009-2010
      pandemic influenza in an Italian adult population.
AB  - OBJECTIVES: To evaluate the response to pandemic vaccination and seasonal and
      pandemic vaccine effectiveness (VE) in an Italian adult population, during the
      2009-2010 influenza season. METHODS: Data were recorded by interviewing 19,275
      subjects (>=35 years), randomly recruited from the general population of the Moli
      sani project. Events [influenza-like illness (ILI), hospitalization and death],
      which had occurred between 1 November 2009 and 31 January 2010 were considered.
      VE was analyzed by multivariable Poisson regression analysis. RESULTS: Pandemic
      vaccine coverage was very low (2.4%) in subjects at high-flu risk, aged 35-65
      years (N = 8,048); there was no significant preventive effect of vaccine against
      ILI. Seasonal vaccine coverage was 26.6% in the whole population (63% in elderly
      and 21.9% in middle-aged subjects at high-flu risk). There was a higher risk to
      develop ILI in middle-age [VE: -17% (95% CI: -35,-1)] or at high flu-risk [VE: 
      17% (95% CI: -39, 2)] vaccinated groups. CONCLUSIONS: Coverage of pandemic
      vaccine was very low in a Southern Italy population, with no protective effect
      against ILI.

PMID- 22371003
TI  - The relationship between job stress and body mass index using longitudinal data
      from Canada.
AB  - OBJECTIVE: This paper examines the effect of job stress, as measured by the job
      strain model (high job demands and low job control) on an individual's body mass
      index (BMI) using data from the Canadian National Population Health Survey.
      METHODS: We use panel data estimation methods to account for unobserved
      individual-level heterogeneity to better examine the relationship between job
      related stress and BMI. RESULTS: Results from the fixed effects and random
      effects models show no statistically significant difference in BMI levels between
      individuals in jobs with high/medium strain compared to jobs with low strain.
      However, in the cross-sectional OLS model, job stress has a positive and
      significant effect on BMI. These analyses control for socio-demographic factors,
      lifestyle behavior, workplace social support, occupational and provincial fixed
      effects. The results suggest that the mixed findings in the previous studies may
      in part be due to unobserved characteristics that cannot be controlled for using
      standard cross-sectional analysis. CONCLUSION: This study results suggest the
      need for further longitudinal evidence in order to have a better understanding of
      the relationship between job stress and body weight.

PMID- 22371004
TI  - Clustering of health and risk behaviour in immigrant and indigenous Dutch
      residents aged 19-40 years.
AB  - OBJECTIVES: Studies on the co-occurrence, 'clustering' of health and other risk
      behaviours among immigrants from non-industrialised countries lack until now. The
      aim of this study was to compare this clustering in immigrant and indigenous
      adults. METHODS: A representative sample (N = 2,982; response 71%) of the Dutch
      population aged 19-40, with 247 respondents from non-industrialized countries
      (Turkey, Morocco, Surinam, Netherlands Antilles), was asked about health
      behaviours (alcohol, smoking, drugs, unsafe sex, exercise, nutrition, sleep
      behaviour, traffic behaviour), and about rule-breaking behaviour and aggression.
      Data were collected using internet questionnaires, which excluded respondents
      unable to read Dutch. RESULTS: Among indigenous adults, health and risk
      behaviours co-occur in three clusters (alcohol, health-enhancing behaviour, and
      rule-breaking behaviour), whereas among immigrant groups two clusters were found
      (alcohol and rule-breaking behaviour/smoking). Differences mostly concerned
      health-enhancing behaviours such as nutrition, which was not part of any cluster,
      and physical activity. CONCLUSIONS: This supports an integrated promotion of
      healthier lifestyles to immigrants who are able to read Dutch. Regarding
      potentially risky behaviours like alcohol use and rule-breaking behaviours, this
      could be similar to that for indigenous people.

PMID- 22371005
TI  - Fathers' knowledge of and attitude towards human papillomavirus infection,
      genitoanal warts, cervical cancer and HPV vaccine.

PMID- 22371006
TI  - HPV vaccination coverage within 3 years of program launching (2008-2011) at
      Geneva State, Switzerland.
AB  - OBJECTIVE: The objective of this study is to assess the HPV vaccination coverage
      of 11-19-year-old girls during a state-coordinated HPV vaccination program in
      Geneva, Switzerland, from September 2008 to June 2011. METHODS: State Medical
      Office coordinated the HPV vaccination program. Each service provider transmitted
      the list of the persons who had received their first, second, or third shot.
      RESULTS: The global coverage rates, 3 years after the program had been launched,
      were 63.72% for one dose, 63.22% for two doses, and 61.40% for three doses of the
      HPV vaccine. CONCLUSION: This study shows that it is possible to obtain a good
      coverage rates after 3 years of a state-coordinated HPV vaccination program.

PMID- 22371008
TI  - Flexible protein-ligand docking using the Fleksy protocol.
AB  - Considering protein plasticity is important in accurately predicting the three
      dimensional geometry of protein-ligand complexes. Here, we present the first
      public release of our flexible docking tool Fleksy, which is able to consider
      both ligand and protein flexibility in the docking process. We describe the
      workflow and different features of the software and present its performance on
      two cross-docking benchmark datasets.

PMID- 22371007
TI  - The impaired immune regulation of autoimmune hepatitis is linked to a defective
      galectin-9/tim-3 pathway.
AB  - In autoimmune hepatitis (AIH), liver-damaging CD4 T cell responses are associated
      with defective CD4(pos) CD25(pos) regulatory T cells (T-regs). Galectin-9 (Gal9),
      a beta-galactosidase-binding protein expressed by T-regs, is key to their
      function, inhibiting T helper 1 immune responses by binding T cell immunoglobulin
      and mucin domain 3 (Tim-3) on CD4 effector cells. We investigated whether
      impaired immunoregulation in AIH results from reduced expression of Gal9 in T
      regs and/or Tim-3 on CD4 effector cells. Circulating Gal9(pos) CD4(pos) CD25(pos)
      and Tim-3(pos) CD4(pos) CD25(neg) T cell phenotype was assessed by flow cytometry
      in 75 AIH patients. To evaluate whether Tim-3 expression renders CD4(pos)
      CD25(neg) T cells amenable to T-reg control, purified CD4(pos) CD25(neg) Tim
      3(pos) (Tim-3(pos)) and CD4(pos) CD25(neg) Tim-3(neg) (Tim-3(neg)) cells were
      cocultured with T-regs. To determine whether Gal9 expression is essential to
      function, T-regs were treated with small interfering RNA (siRNA) to repress Gal-9
      translation; T-reg suppressor function was assessed by proliferation. In AIH, Tim
      3(pos) cells within CD4(pos) CD25(neg) cells and their T-bet(pos) and RORC(pos)
      subsets were fewer and contained higher numbers of interferon-gamma
      (IFNgamma)(pos) and interleukin (IL)-17(pos) cells than healthy subjects (HS). In
      AIH and HS, Tim-3(pos) cells proliferated less vigorously and were more
      susceptible to T-reg control than Tim-3(neg) cells. In AIH, Gal9(pos) T-regs were
      fewer and contained less FOXP3(pos), IL-10(pos), and transforming growth factor
      beta(pos) and more IFNgamma(pos) and IL-17(pos) cells than HS. siRNA treatment of
      Gal-9(pos) T-regs drastically reduced T-reg ability to suppress CD4(pos)
      CD25(neg) and Tim-3(pos) cell proliferation in AIH and HS. Tim-3(pos) cell
      percentage correlated inversely with aminotransferase and CD25(neg) T-bet(pos)
      cell values. CONCLUSION: Reduced levels of Tim-3 on CD4(pos) CD25(neg) effector
      cells and of Gal9 in T-regs contribute to impaired immunoregulation in AIH by
      rendering effector cells less prone to T-reg control and T-regs less capable of
      suppressing.

PMID- 22371009
TI  - The ecotoxicological recovery of Ely Creek and tributaries (Lee County, VA) after
      remediation of acid mine drainage.
AB  - The Ely Creek watershed (Lee County, VA) was determined in 1995 to be the most
      negatively affected by acid mine drainage (AMD) within the Virginia coalfield.
      This determination led the US Army Corps of Engineers to design and build passive
      wetland remediation systems at two major AMD seeps affecting Ely Creek. This
      study was undertaken to determine if ecological recovery had occurred in Ely
      Creek. The results indicate that remediation had a positive effect on all
      monitoring sites downstream of the remediated AMD seeps. At the site most
      impacted by AMD, mean pH was 2.93 prior to remediation and improved to 7.14 in
      2004. Benthic macroinvertebrate surveys revealed that one AMD influenced site had
      increased taxa richness from zero taxa in 1997 to 24 in 2004. While in situ
      testing of Asian clams resulted in zero survival at five of seven AMD influenced
      sites prior to remediation, some clams survived at all sites after. Clam survival
      was found to be significantly less than upstream references at only two sites,
      both downstream of un-mitigated AMD seeps in 2004. An ecotoxicological rating
      (ETR) system that combined ten biotic and abiotic parameters was developed as an
      indicator of the ecological status for each study site. A comparison of ETRs from
      before and after remediation demonstrated that all sites downstream of the
      remediation had experienced some level of recovery. Although the remediation has
      improved the ecological health of Ely Creek, un-mitigated AMD discharges are
      still negatively impacting the watershed.

PMID- 22371010
TI  - N-Ion-implanted TiO2 photoanodes in quantum dot-sensitized solar cells.
AB  - Hierarchical nanostructured titanium dioxide (TiO(2)) clumps were fabricated
      using electrostatic spray with subsequent nitrogen-ion doping by an ion
      implantation technique for improvement of energy conversion efficiency for
      quantum dot-sensitized solar cells (QDSCs). CdSe quantum dots were directly
      assembled on the produced N-ion-implanted TiO(2) photoanodes by chemical bath
      deposition, and their photovoltaic performance was evaluated in a polysulfide
      electrolyte with a Pt counter electrode. We found that the photovoltaic
      performance of TiO(2) electrodes was improved by nearly 145% upon N-ion
      implantation. The efficiency improvement seems to be due to (1) the enhancement
      of electron transport through the TiO(2) layer by inter-particle necking of
      primary TiO(2) particles and (2) an increase in the recombination resistance at
      TiO(2)/QD/electrolyte interfaces by healing the surface states or managing the
      oxygen vacancies upon N-ion doping. Therefore, N-ion-doped photoanodes offer a
      viable pathway to develop more efficient QD or dye-sensitized solar cells.

PMID- 22371012
TI  - Can parent reports serve as a proxy for teacher ratings in medication management
      of attention-deficit hyperactivity disorder?
AB  - OBJECTIVE: While American Academy of Pediatrics guidelines recommend obtaining
      symptom reports from both parents and teachers when treating children with
      attention-deficit hyperactivity disorder (ADHD), information from parents is
      easier to obtain and practitioners may prefer to rely solely on parent report
      when managing medications. There are, however, few empirical data on the
      relationship between parent and teacher reports during medication management of
      ADHD. This study examined the relationship between parent and teacher reports of
      symptoms of ADHD during a clinical trial. METHODS: A study to improve medication
      management of ADHD was conducted in 24 pediatric practices with 270 children.
      Children meeting criteria for ADHD were randomized by practice to treatment-as
      usual or specialized care groups, with data combined from the groups to examine
      parent-teacher agreement. Parent and teacher reports on the ADHD Rating Scale-IV
      were obtained at pretreatment, 4 months, and 12 months follow-up. RESULTS: At
      each assessment, correlations between parent and teacher ratings were
      statistically significant, but the magnitudes of the correlations were low,
      accounting for no more than approximately 17% of the variance between measures.
      Correlations between change scores on parent and teacher ratings were
      statistically significant but low for Total and Inattentive scales and not
      significant for the Hyperactive-Impulsive scale. For agreement on extreme scores,
      6 of 9 kappas were statistically significant but all were unacceptably low.
      CONCLUSIONS: Agreement between parent and teacher ratings of symptoms of ADHD is
      too low for clinicians to rely on parent reports while managing medications.
      Teacher reports are still needed to ensure optimal management.

PMID- 22371011
TI  - Overexpression of wild-type or mutants forms of CEBPA alter normal human
      hematopoiesis.
AB  - CCAAT/enhancer-binding protein-alpha (C/EBPalpha/CEBPA) is mutated in
      approximately 8% of acute myeloid leukemia (AML) in both familial and sporadic
      AML and, with FLT3 and NPM1, has received most attention as a predictive marker
      of outcome in patients with normal karyotype disease. Mutations clustering to
      either the N- or C-terminal (N- and C-ter) portions of the protein have different
      consequences on the protein function. In familial cases, the N-ter form is
      inherited with patients exhibiting long latency period before the onset of overt
      disease, typically with the acquisition of a C-ter mutation. Despite the
      essential insights murine models provide the functional consequences of wild-type
      C/EBPalpha in human hematopoiesis and how different mutations are involved in AML
      development have received less attention. Our data underline the critical role of
      C/EBPalpha in human hematopoiesis and demonstrate that C/EBPalpha mutations
      (alone or in combination) are insufficient to convert normal human hematopoietic
      stem/progenitor cells into leukemic-initiating cells, although individually each
      altered normal hematopoiesis. It provides the first insight into the effects of N
      and C-ter mutations acting alone and to the combined effects of N/C double
      mutants. Our results mimicked closely what happens in CEBPA mutated patients.

PMID- 22371013
TI  - Changes caused by haloperidol are blocked by music in Wistar rat.
AB  - This study sought to evaluate the effect of classical music, using Mozart's
      sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the
      striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on
      prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were
      divided into four groups: (1) control, (2) haloperidol treatment (single dose of
      2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus
      music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a
      fall in plasma PRL and corticosterone levels in healthy rats (P < 0.05) and
      prevented the increase in levels triggered by haloperidol (P < 0.001). Moreover,
      exposure to music was associated with a significant increase in DA levels in all
      groups, with the increase being particularly marked in PFC and SN (P < 0.001).
      Haloperidol is a recognised D2 receptor antagonist, and these findings suggest
      that music, by contrast, enhances DA activity and turnover in the brain. The
      results obtained here bear out reports that music triggers a reduction in
      systolic pressure and an increase in mesencephalon dopamine levels in human and
      rats treated with ecstasy, through a calmodulin-dependent system.

PMID- 22371014
TI  - Modulation of biogenic amines content by poly(propylene imine) dendrimers in
      rats.
AB  - Biogenic amines and polyamines participate in all vital organism functions, their
      levels being important function determinants. Studies were performed to check
      whether repeated administration of poly(propylene imine) (PPI) dendrimers,
      synthetic macromolecules with diaminobutane core, and peripheral primary amine
      groups, may influence the endogenous level of amines, as represented by the two
      of them: spermidine, a natural derivative of diaminobutane, and histamine. The
      experiment was carried out on Wistar rats. Fourth generation PPI dendrimer, as
      well as maltotriose-modified fourth generation PPI dendrimers with (a) cationic
      open sugar shell and (b) neutral dense sugar shell that possess a higher
      biocompatibility, was used. Applying the combination of column chromatography on
      Cellex P and spectrofluorimetric assays of o-phthaldialdehyde, the final amine
      condensation products were employed to analyze tissue spermidine and histamine
      outside the central nervous system. Furthermore, radioenzymatic assay was used to
      measure histamine levels in the brain. The obtained results indicate that in some
      tissues, the endogenous concentrations of histamine and spermidine may be
      affected by dendrimers depending on their dose and type of dendrimers.

PMID- 22371015
TI  - Estrogens: mechanisms of neuroprotective effects.
AB  - Within the last few years, there has been a growing interest in the
      neuroprotective effects of estrogen and the possible beneficial effects of
      estrogen in neurodegenerative diseases such as stroke, Alzheimer's disease, and
      Parkinson's disease. The concept of neuroprotective effects of estrogen in women
      remains controversial because these effects may vary with the timing of
      treatment. Research increasingly suggests that changes in estrogen levels during
      aging may increase risk for Alzheimer's disease, the most common type of
      dementia. This update reviews the newest information about estrogen and cognitive
      aging, including information regarding the role of bioavailable estrogen in older
      women and men.

PMID- 22371016
TI  - Micro-array profiling exhibits remarkable intra-individual stability of human
      platelet micro-RNA.
AB  - Platelets play an important role in haemostasis and thrombus formation. Latest
      research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are
      short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited
      data exist on inter-individual variability of platelet miRNA profile while no
      data are available on intra-individual variability. We assessed platelet miRNA
      profile in five volunteers at five time points over a time course of 10 days; 24
      hours prior to the last blood sampling, subjects took 500 mg acetylsalicylic acid
      (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma,
      and miRNA array-analysis was performed. Temporal patterns and ASA effect were
      explored by a linear mixed effects model for each miRNA. For the 20 most
      abundantly expressed platelet miRNAs, target gene search was performed and an
      annotation network was created. MiRNA expression profiling of 1,281 human miRNAs
      revealed relevant expression of 221 miRNAs consistently expressed in all samples
      at all time points. Correlation of platelet miRNA ranks was highly significant to
      other studies. Global distribution of miRNA expression was relatively similar in
      all subjects. No miRNA exhibited a significant effect of time at level 0.05.
      After 24 hours, no significant effect of ASA was found. Concerning functional
      implications of the 20 most abundantly expressed miRNAs, we found six functional
      themes. In conclusion, platelet miRNA profile is remarkably stable over the time
      period studied. Single-point analysis of platelet miRNA profile is reasonable
      when inter-individual differences are studied. The functional annotation network
      points toward extra-platelet effects of platelet miRNAs.

PMID- 22371017
TI  - Synchronous oral paracoccidioidomycosis and esophageal carcinoma.
AB  - Paracoccidioidomycosis is the most common deep mycosis in South America and is
      caused by Paracoccidioides brasiliensis (P. brasiliensis), a thermally dimorphic
      fungus. Infections usually occur by inhalation of conidia, which more often cause
      respiratory, mucocutaneous, and lymph nodal changes. Chronic features of this
      mycosis can mimic diverse infections and malignancies and constitute diagnosis
      challenges. Squamous cell carcinoma deserves special attention in this setting.
      We describe the case of a patient with synchronous diagnosis of oral
      paracoccidioidomycosis and esophageal squamous cell carcinoma. Concomitance of
      these conditions may be a casual event, but a not fully understood causal
      relationship can be involved.

PMID- 22371018
TI  - Composite resin reinforced with pre-tensioned fibers: a three-dimensional finite
      element study on stress distribution.
AB  - Pre-tensioned construction material is utilized in engineering applications of
      high strength demands. The purpose of this study was to evaluate the effect of
      the pre-tensioning fibers of fiber-reinforced composite (FRC) using three
      dimensional finite element (FE) analysis. The 3D FE models of particulate
      composite resin (CR), FRC and composite resin reinforced with pre-tensioned
      fibers (PRE-T-FRC) were constructed. The uniaxial three-point bending test was
      simulated using FE analysis to calculate the principal stress distribution. In
      the FRC and PRE-T-FRC, stresses were higher than CR, and they were located in the
      fiber. However, the maximum principal stress value at the composite of PRE-T-FRC
      was lower than the FRC and CR. Composite resin reinforced with pre-tensioned
      fibers was advantageous for stress distribution and lowering the stress at the
      composite itself. Experimental studies on physical properties of pre-tensioned
      FRC are encouraged to be conducted.

PMID- 22371019
TI  - CORAL: QSAR models for acute toxicity in fathead minnow (Pimephales promelas).
AB  - CORrelation And Logic (CORAL) is a software that generates quantitative structure
      activity relationships (QSAR) for different endpoints. This study is dedicated to
      the QSAR analysis of acute toxicity in Fathead minnow (Pimephales promelas).
      Statistical quality for the external test set is a complex function of the split
      (into training and test subsets), the number of epochs of the Monte Carlo
      optimization, and the threshold that is a criterion for dividing the correlation
      weights into two classes rare (blocked) and not rare (active). Computational
      experiments with three random splits (data on 568 compounds) indicated that this
      approach can satisfactorily predict the desired endpoint (the negative decimal
      logarithm of the 50% lethal concentration, in mmol/L, pLC50). The average
      correlation coefficients (r2) are 0.675 +/- 0.0053, 0.824 +/- 0.0242, 0.787 +/-
      0.0101 for subtraining, calibration, and test set, respectively. The average
      standard errors of estimation (s) are 0.837 +/- 0.021, 0.555 +/- 0.047, 0.606 +/-
      0.049 for subtraining, calibration, and test set, respectively. The CORAL
      software together with three random splits into subtraining, calibration, and
      test sets can be downloaded on the Internet (http://www.insilico.eu/coral/).

PMID- 22371020
TI  - Long-term evaluation of the central vault after phakic Collamer(r) lens (ICL)
      implantation using OCT.
AB  - PURPOSE: The aim of this work is to evaluate the changes in the central vault
      after using implantable Collamer(r) lenses (ICL) to correct myopia. METHODS: This
      cohort study included 133 eyes; mean spherical equivalent -9.47 +/- 3.71 diopters
      (D) (range: -2.75 to -22.25 D) who underwent ICL V4 implantation. Besides a
      complete ophthalmologic examination, the central vaulting was measured with
      Visante OCT and evaluated between different periods of follow-up (1 week, 1, 3,
      and 6 months, and yearly postoperatively). Post-operative time ranged from 6 to
      73 months. RESULTS: Within the first 6 months, the mean central vaulting dropped
      from 510 +/- 238 MUm (range 100 to 940 MUm) to 439 +/- 231 MUm (range 90 to 910)
      a significant decrease by 71 +/- 58 MUm (range -170 to 30 MUm) (p = 0.028) with a
      trend to a lower reduction after this period. After 36 month from ICL
      implantation, this variation tends to be smaller with the majority of the eyes
      having a mean decrease smaller than 2 MUm per month. Initial vault (Spearman Rho
      = -0.237, p = 0.006) was the factor more significantly associated with decrease
      in vault; eyes presenting a reduction in vault >100 MUm had an average initial
      vault that was 141 MUm and 184 MUm higher than eyes with no change or with
      increase in vault over time, respectively. CONCLUSIONS: This study shows a
      continuous reduction of central vault over time. The reduction is highest during
      the first 6 months and tends to be lower and slow down over time. The decrease of
      vaulting was more pronounced in eyes with larger initial vaulting.

PMID- 22371021
TI  - Surface epithelialization of the type I Boston keratoprosthesis front plate:
      immunohistochemical and high-definition optical coherence tomography
      characterization.
AB  - BACKGROUND: The aim of this work is to characterize a transparent tissue layer
      partially covering the anterior surface of the type I Boston permanent
      keratoprosthesis front plate in four patients. METHODS: The tissue over the front
      plate was easily scrolled back as a single transparent layer using a sponge. In
      two cases, histopathologic analysis was undertaken and immunofluorescent staining
      with a cytokeratin 3-specific antibody was performed. The relationship of the
      tissue to the keratoprosthesis device was further characterized using spectral
      domain high-definition optical coherence tomography (HD-OCT). RESULTS:
      Histopathologic analysis revealed the tissue to be non-keratinized squamous
      epithelium. No goblet cells were seen, suggesting the cells were of corneal, and
      not conjunctival, epithelial origin. Immunofluorescent staining of all cells was
      positive for cytokeratin 3, a protein strongly associated with corneal
      epithelium. The tissue was easily discerned by HD-OCT and was of substantial
      thickness near the external junction between the keratoprosthesis device and the
      carrier corneal tissue. In three cases, visual acuity was unaffected by the
      presence or absence of this tissue. In one case, a prominent tissue margin
      temporarily obscured the visual axis and reduced visual acuity; this resolved
      with mechanical central debridement and has not recurred. CONCLUSIONS: The
      transparent tissue layer covering the anterior surface of the type I Boston
      keratoprosthesis front plate was found to represent non-keratinized squamous
      epithelium, most likely of corneal epithelial origin. This potentially represents
      a further step in bio-integration of the keratoprosthesis device. In particular,
      epithelial coverage of the critical junction between the device and the carrier
      corneal tissue might serve an important barrier function and further reduce the
      incidence of infection and extrusion of the type I Boston permanent
      keratoprosthesis.

PMID- 22371022
TI  - Delayed superior forniceal CSF accumulation and conjunctival prolapse after
      superior orbital wall fracture.

PMID- 22371023
TI  - Analysis of optical side-effects of fs-laser therapy in human presbyopic lens
      simulated with modified contact lenses.
AB  - BACKGROUND: In a single-blinded study, optical side-effects of a potential
      femtosecond (fs)-laser therapy in presbyopic human lenses were tested. Simulation
      of this therapy was carried out by applying fs-laser patterns into standard
      contact lenses (CL). METHODS: In the first part of the study, the influence of
      the numerical aperture on optical side-effects was investigated by comparing a
      typical fs-LASIK configuration to a fs-presbyopia treatment (n = 11). The second
      part focused on a possible improvement of visual performance by comparing a
      regular grid pattern to a randomly chosen spacing of the laser spots (n = 16).
      Visual acuity was measured with ETDRS charts, contrast sensitivity with F.A.C.T.
      charts and mesopic vision with Mesotest II. Forward scattered light was measured
      with the C-Quant (both instruments: Oculus Optikgerate GmbH, Germany). A
      questionnaire detected subjective quality of vision. Differences between laser
      treated and untreated CL and among the modifications were analyzed. RESULTS: The
      laser-treated and standard CL indicated no significant difference in visual
      acuity, contrast sensitivity and mesopic vision without glare. While wearing
      modified lenses with a regular grid, quality of vision decreased significantly by
      means of mesopic vision with glare and subjective straylight. These modifications
      also caused an impairment of subjective quality of vision. In contrast, there was
      no significant difference between the random pattern and standard CL. CONCLUSION:
      The increase of optical side-effects was reproducibly dependent on the geometry
      of the laser-structure. A randomized grid induced the least limitation. The study
      results are useful for planning possible laser-patterns in fs-laser therapy of
      the presbyopic lens.

PMID- 22371024
TI  - An association between environmental factors and the IVS4+44C>A polymorphism of
      the DMT1 gene in age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is an ocular disease affecting
      macula - the central part of the retina, resulting in the degeneration of
      photoreceptors and retinal epithelium and causing severe central vision
      impairment. The pathophysiology of the disease is not completely known, but a
      significant role is attributed to genetic factors. The contribution of oxidative
      stress in AMD as a trigger of the degenerative process is well-established. Iron
      ions may act as a source of reactive oxygen species; therefore, maintaining iron
      homeostasis is important for redox balance in the organism. Diversity in iron
      homeostasis genes may counterpart in unbalanced redox state, and thus be involved
      in AMD pathophysiology. METHODS: In this work, we searched for an association
      between some single nucleotide polymorphisms in the divalent metal transporter 1
      (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and
      environmental factors and AMD. Genotyping was performed using the PCR-RFLP
      method. DNA was obtained from 436 AMD patients and 168 controls. RESULTS: We did
      not find any association between the genotypes of the two polymorphisms and AMD
      occurrence. However, we observed that AMD patients living in a rural environment
      and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk
      of AMD, while individuals with the CA genotype or the A allele had a decreased
      risk of the disease. Moreover, in male AMD patients the C allele increased the
      risk of the disease, while the AA genotype decreased it. CONCLUSIONS: These
      results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact
      with place of living and gender to modulate the risk of AMD.

PMID- 22371025
TI  - Clinical characteristics of ocular toxocariasis in Eastern China.
AB  - PURPOSE: To explore the clinical characteristics of patients with ocular
      toxocariasis in eastern China. METHODS: The medical records of 35 cases of ocular
      toxocariasis in Fudan University Eye & ENT Hospital between May 2009 and April
      2011 were retrospectively reviewed and analyzed. UBM, RetCam or fundus imaging,
      and high-frequency or conventional ultrasonography were performed in these
      patients. RESULTS: The mean patient age in our series of ocular toxocariasis was
      11.86 +/- 8.80 years. There were 28 children and seven adults, the majority
      residing in a rural area (88.57%). All cases were classified into three clinical
      subtypes: granuloma in the peripheral retina (60% of cases); granuloma in the
      posterior pole (28.57% of cases); and vitreous inflammation mimicking chronic
      endophthalmitis (5.71% of cases). We also identified an additional subtype with
      unique clinical features that we termed "combined type" presenting in 5.71% of
      our patients. This subtype exhibited granulomas in both the posterior pole and
      peripheral retina. RetCam fundus imaging was able to identify granulomas in the
      posterior and peripheral subtypes, 100% and 80.95% of cases respectively.
      Moreover, UBM combined with conventional ultrasonography identified granulomas in
      95% of the peripheral subtype cases and in 100% of the posterior pole subtype
      cases. CONCLUSIONS: This is the first ocular toxocariasis series described in
      Chinese patients. Compared with reports from developed countries, the ocular
      features in our series were more severe and complicated, presenting with poorer
      visual acuity and a high rate of retinal detachment (45.7%). The application of
      RetCam and UBM during examination in ocular toxocariasis can provide valuable
      information in determining the severity of disease and features important in
      considering surgical procedures in such patients.

PMID- 22371026
TI  - Hepatitis A virus vaccination in persons with hepatitis C virus infection:
      consequences of quality measure implementation.
AB  - Hepatitis A virus (HAV) superinfection in persons with hepatitis C virus (HCV)
      infection has been associated with a high mortality rate, and vaccination is
      recommended. The incidence of HAV is low, and the aim of this study was to
      determine the mortality risk of HAV superinfection and the consequences of
      routine vaccination in persons with HCV infection. To determine the mortality
      risk of HAV superinfection, a meta-analysis including studies reporting mortality
      in HCV-infected persons was performed. Data were extracted independently by two
      investigators and recorded on a standardized spreadsheet. The pooled mortality
      estimate was used to determine the number needed to vaccinate (NNV) to prevent
      mortality from HAV superinfection. The total vaccine cost was also calculated. A
      total of 239 studies were identified using a defined search strategy. Of these,
      11 appeared to be relevant, and of these, 10 were suitable for inclusion in the
      meta-analysis. The pooled odds ratio (OR) for mortality risk in HAV
      superinfection of HCV-infected persons was 7.23 (95% confidence interval: 1.24
      42.12) with significant heterogeneity (I(2) = 56%; P = 0.03) between studies.
      Using the pooled OR for mortality, this translates to 1.4 deaths per 1,000,000
      susceptible persons with HCV per year. The NNV to prevent one death per year is
      therefore 814,849, assuming 90% vaccine uptake and 94.3% vaccine efficiency. The
      vaccine cost for this totals $162 million, or $80.1 million per death prevented
      per year. CONCLUSION: These data challenge the use of routine HAV vaccination in
      HCV-infected persons and its incorporation into clinical practice guidelines. HAV
      vaccination of all HCV-infected persons is costly and likely to expose many
      individuals to an intervention that is of no direct benefit.

PMID- 22371027
TI  - Effect of Grade I and II intraventricular hemorrhage on visuocortical function in
      very low birth weight infants.
AB  - The neurological outcome for infants with Grade I/II intraventricular hemorrhage
      (IVH) is debated. The aim of this study was to determine whether very low birth
      weight infants (VLBW, <1500 g) with Grade I/II (IVH) have altered visuocortical
      activity compared with infants  with no IVH. We assessed the quantitative swept
      parameter visual evoked potential (sVEP) responses evoked by three different
      visual stimuli. Data from 52 VLBW infants were compared with data from 13 infants
      with Grade I or II IVH, enrolled at 5-7 months corrected age. Acuity thresholds 
      and suprathreshold response amplitudes were compared. Grating acuity (GA),
      contrast sensitivity (CS) and vernier acuity (VA) were each worse in the Grade
      I/II IVH compared with the no IVH groups (8.24 cpd in IVH group vs. 13.07 cpd in
      no IVH group for GA; 1.44% vs. 1.18%  for CS and 1.55 arcmin vs. 0.58 arcmin for
      VA). The slopes of the response amplitude for CS and VA were significantly lower
      in IVH infants. The spatial frequency tuning function was shifted downward on the
      spatial frequency axis, without a change in slope. These results indicate that 
      Grade I/II IVH are associated with deleterious effects on cortical vision
      development and function.

PMID- 22371028
TI  - MAME models for 4D live-cell imaging of tumor: microenvironment interactions that
      impact malignant progression.
AB  - We have developed 3D coculture models, which we term MAME (mammary architecture
      and microenvironment engineering), and used them for live-cell imaging in real
      time of cell:cell interactions.  Our overall goal was to develop models that
      recapitulate the architecture of preinvasive breast lesions to study their
      progression to an invasive phenotype.  Specifically, we developed models to
      analyze interactions among pre-malignant breast epithelial cell variants and
      other cell types of the tumor microenvironment that have been implicated in
      enhancing or reducing the progression of preinvasive breast epithelial cells to
      invasive ductal carcinomas.  Other cell types studied to date are myoepithelial
      cells, fibroblasts, macrophages and blood and lymphatic microvascular endothelial
      cells.  In addition to the MAME models, which are designed to recapitulate the
      cellular interactions within the breast during cancer progression, we have
      developed comparable models for the progression of prostate cancers.     Here we
      illustrate the procedures for establishing the 3D cocultures along with the use
      of live-cell imaging and a functional proteolysis assay to follow the transition
      of cocultures of breast ductal carcinoma in situ (DCIS) cells and fibroblasts to
      an invasive phenotype over time, in this case over twenty-three days in culture. 
      The MAME cocultures consist of multiple layers. Fibroblasts are embedded in the
      bottom layer of type I collagen.  On that is placed a layer of reconstituted
      basement membrane (rBM) on which DCIS cells are seeded.  A final top layer of 2%
      rBM is included and replenished with every change of media.  To image proteolysis
      associated with the progression to an invasive phenotype, we use dye-quenched
      (DQ) fluorescent matrix proteins (DQ-collagen I mixed with the layer of collagen
      I and DQ-collagen IV mixed with the middle layer of rBM) and observe live
      cultures using confocal microscopy. Optical sections are captured, processed and
      reconstructed in 3D with Volocity visualization software.  Over the course of 23
      days in MAME cocultures, the DCIS cells proliferate and coalesce into large
      invasive structures.  Fibroblasts migrate and become incorporated into these
      invasive structures.  Fluorescent proteolytic fragments of the collagens are
      found in association with the surface of DCIS structures, intracellularly, and
      also dispersed throughout the surrounding matrix.  Drugs that target proteolytic,
      chemokine/cytokine and kinase pathways or modifications in the cellular
      composition of the cocultures can reduce the invasiveness, suggesting that MAME
      models can be used as preclinical screens for novel therapeutic approaches.

PMID- 22371029
TI  - Characterization of a highly pathogenic H5N1 avian influenza virus isolated from
      ducks in Eastern China in 2011.
AB  - This study describes the characterization of seven H5N1 avian influenza viruses
      from domestic ducks in Eastern China in 2011. Phylogenetic analysis showed these
      viruses were closely related to an H5N1 virus circulating in wild birds in Hong
      Kong. Some characteristics of these viruses were similar to those of an H5N1
      strain that circulated in China and Vietnam (2003-2004). The virulence of three
      isolates was examined in chickens and mice, and they were found to be highly
      pathogenic in chickens but showed low pathogenicity in mice. These results
      suggest that continued H5N1 surveillance in poultry should be used as an early
      warning system for avian influenza outbreaks.

PMID- 22371030
TI  - Letter to the editor: The role of shallow water habitats in human evolution: a
      response to Herries et al., 2010 critique of Wrangham et al., 2009.

PMID- 22371031
TI  - Metrics-based assessments of research: incentives for 'institutional plagiarism'?
AB  - The issue of plagiarism--claiming credit for work that is not one's own, rightly,
      continues to cause concern in the academic community. An analysis is presented
      that shows the effects that may arise from metrics-based assessments of research,
      when credit for an author's outputs (chiefly publications) is given to an
      institution that did not support the research but which subsequently employs the
      author. The incentives for what is termed here "institutional plagiarism" are
      demonstrated with reference to the UK Research Assessment Exercise in which
      submitting units of assessment are shown in some instances to derive around twice
      the credit for papers produced elsewhere by new recruits, compared to papers
      produced 'in-house'.

PMID- 22371032
TI  - Science, ethics and war: a pacifist's perspective.
AB  - This article considers the ethical aspects of the question: should a scientist
      engage in war-related research, particularly use-inspired or applied research
      directed at the development of the means for the better waging of war? Because
      scientists are simultaneously professionals, citizens of a particular country,
      and human beings, they are subject to conflicting moral and practical demands.
      There are three major philosophical views concerning the morality of war that are
      relevant to this discussion: realism, just war theory and pacifism. In addition,
      the requirements of professional codes of ethics and common morality contribute
      to an ethical analysis of the involvement of scientists and engineers in war
      related research and technology. Because modern total warfare, which is
      facilitated by the work of scientists and engineers, results in the inevitable
      killing of innocents, it follows that most, if not all, war-related research
      should be considered at least as morally suspect and probably as morally
      prohibited.

PMID- 22371033
TI  - Corruption and internal fraud in the Turkish construction industry.
AB  - The purpose of this paper is to develop an understanding about the internal fraud
      and corruption problem in the Turkish construction industry. The reasons behind
      the internal fraud and corruption problem as well as the types of prevention
      methods were investigated; and as a result various recommendations were made. To
      this end, a risk awareness questionnaire was used to understand the behavioral
      patterns of the construction industry, and to clarify possible proactive and
      reactive measures against internal fraud and corruption. The type of fraud
      experienced by Turkish construction companies was also surveyed in the
      questionnaire. The questionnaire was sent to 89 firms; and depending on the
      collected data, certain recommendations for construction industry professionals
      were provided.

PMID- 22371034
TI  - The Just War Theory and the ethical governance of research.
AB  - This article analyses current trends in and future expectations of nanotechnology
      and other key enabling technologies for security as well as dual use
      nanotechnology from the perspective of the ethical Just War Theory (JWT),
      interpreted as an instrument to increase the threshold for using armed force for
      solving conflicts. The aim is to investigate the relevance of the JWT to the
      ethical governance of research. The analysis gives rise to the following results.
      From the perspective of the JWT, military research should be evaluated with
      different criteria than research for civil or civil security applications. From a
      technological perspective, the boundaries between technologies for civil and
      military applications are fuzzy. Therefore the JWT offers theoretical grounds for
      making clear distinctions between research for military, civil security and other
      applications that are not obvious from a purely technological perspective.
      Different actors bear responsibility for development of the technology than for
      resorting to armed force for solving conflicts or for use of weapons and military
      technologies in combat. Different criteria should be used for moral judgment of
      decisions made by each type of actor in each context. In addition to evaluation
      of potential consequences of future use of the weapons or military technologies
      under development, the JWT also prescribes ethical evaluation of the inherent
      intent and other foreseeable consequences of the development itself of new
      military technologies.

PMID- 22371035
TI  - The trace element content of top-soil and wild edible mushroom samples collected
      in Tuscany, Italy.
AB  - The amount of the trace elements As, Ba, Cd, Cr, Cu, Hg, Li, Mn, Ni, Pb, Rb, Se,
      Sr, and Zn was measured in top soils and edible mushrooms, Boletus edulis,
      Macrolepiota procera, collected at five distinct green microhabitats inside the
      Lucca province, North-Central Italy (years 2008-2009). Results showed a top soil
      element content within the Italian statutory limits. Concerning the amount of
      mushroom elements, we observed significant species-differences obtaining higher
      levels of Ni, Rb, and Se in B. edulis or As, Pb, Cu in M. procera.
      Bioaccumulation factors (BCFs: element in mushroom/element in soil) resulted
      species-dependent and element-selective: in particular, B. edulis preferentially
      accumulated Se (BCFs varying from 14 to 153), while M. procera mainly
      concentrated Cu (BCFs varying from 5 to 15). As well, both species displayed
      between-site BCF differences. By a multivariate principal component approach,
      cluster analysis (CA), we could resolve two main clusters of soil element
      composition, corresponding to the most ecologically divergent sites. Besides, CA
      showed no cluster relating to element contents of B. edulis at the different
      collection sites, while a separation in groups was found for M. procera
      composition with respect to harvesting locations, suggesting uptake systems, in
      this saprotrophic species, sensitive to microhabitat. Regarding consumer safety,
      Cd, Hg, Pb levels resulted sometime relevant in present samples, never reaching
      values from current literature on mushrooms collected in urban-polluted areas.
      Our findings encourage a deeper assessment of the molecular mechanisms of metal
      intake by edible mushrooms, encompassing genetic biochemical and geo-ecological
      variables, with particular awareness to element bioavailability in soils and
      fungi.

PMID- 22371036
TI  - Ecotoxicological impact assessment of some heavy metals and their distribution in
      some fractions of mangrove sediments from Red Sea, Egypt.
AB  - The total and fraction concentrations of heavy metals (Mn, Cu, Ni, Pb, Co, and
      Cd) were analyzed in some sediment fractions (Phi2, Phi3, Phi4, Phi5) of selected
      mangrove ecosystems collected from the Egyptian Red Sea shoreline. The results
      revealed that manganese had the highest mean value (133 +/- 97 mg/kg) followed by
      copper (49.9 +/- 46.0 mg/kg), nickel (28.1 +/- 11.8 mg/kg), lead (19 +/- 13
      mg/kg), cobalt (6.7 +/- 4.0 mg/kg), and cadmium (3.327 +/- 1.280 mg/kg). The
      concentrations of heavy metals in the different sediment fractions showed that
      there was a preferential accumulation of Cu, Co, Mn, and to a lesser degree Cd in
      the silt and clay fractions rather than in the sand-sized. The sediment quality
      was performed by using some sediment quality guidelines. Additionally, the
      contamination and the risk assessment of these heavy metals were achieved by
      different methods including, potential ecological risk index, contamination
      factor, pollution load index, and geoaccumulation index. According to the
      Sediment Quality Guidelines comparisons, the concentrations of Mn and Pb were low
      and showed no possibility of detrimental effects on the local environment. The
      levels of Cu and Ni were high, however, could not be considered to present
      serious threat to the mangrove ecosystem. The data showed that the mangrove
      ecosystems were affected by the Cd risk.

PMID- 22371037
TI  - An indicative method for determination of the most hazardous changes in slopes of
      the subsidence basins in underground coal mining area in Ostrava (Czech
      Republic).
AB  - Considering growing population and decreasing mineral resource reserves, the
      issue of undermining has been and shall remain very topical. This study aims to
      identify the mutual connections between mined out panels of a deposit and the
      final manifestations on the ground surface related to deep black coal mining. On
      the grounds of the identified connections, the study describes a method to
      simplify a common evaluation of undermined areas according to building site
      categories. Within the study, a demarcation of the areas was conducted in two
      localities in Czech Republic influenced by the effects of undermining in the
      Upper-Silesian Basin. In the allotment of the CSM Mine, an area unsuitable for
      founding structures was defined from the centre of the worked out workings to the
      distance of 175 m from the panel's edge, for which the corresponding break angle
      is 78.3 degrees . Similarly, in the allotment of the Paskov Mine, an area
      unsuitable for founding structures was determined to the distance of 500 m from
      the panel's edge, for which the corresponding break angle is 50.2 degrees . This
      demarcation may be implemented prior to deposit mining being aware of several
      physical-mechanical parameters of rocks in the deposit's overburden. Having mined
      out a particular section of a deposit, it is recommended to verify the values of
      break angle using the method described herein. The study may be applied as a
      relatively fast and effective method to evaluate future land use for planning.

PMID- 22371038
TI  - Trace elements in the livers of cod (Gadus morhua L.) from the Baltic Sea: levels
      and temporal trends.
AB  - This paper presents and discusses the levels and temporal trends of
      concentrations of Cd, Pb, Hg, Cu, Zn, and As in livers and Hg in the muscle
      tissues of cod (Gadus morhua L) from the Baltic Sea during the period 1994-2010.
      Concentrations of Pb, Hg, and Cd exhibited significant downward trends. Cu and Zn
      concentrations exhibited upward trends in the period 1994 to 2010. No trends were
      detected for concentrations of As. The temporal trends identified in heavy metal
      concentrations in cod livers corresponded to the directions of changes in
      concentrations of these elements introduced into the Baltic Sea via river runoff
      and atmospheric emission, and those in surface and deep waters of the Baltic.
      Downward trends in the concentrations of toxic metals in cod livers suggest that
      advantageous changes are occurring in concentrations of heavy metals in the
      environment of the southern Baltic Sea.

PMID- 22371039
TI  - Detection of protein deposition within latent fingerprints by surface-enhanced
      Raman spectroscopy imaging.
AB  - The detection of metabolites is very important for the estimation of the health
      of human beings. Latent fingerprint contains many constituents and specific
      contaminants, which give much information of the individual, such as health
      status, drug abuse etc. For a long time, many efforts have been focused on
      visualizing latent fingerprints, but little attention has been paid to the
      detection of such substances at the same time. In this article, we have devised a
      versatile approach for the ultra-sensitive detection and identification of
      specific biomolecules deposited within fingerprints via a large-area SERS imaging
      technique. The antibody bound to the Raman probe modified silver nanoparticles
      enables the binding to specific proteins within the fingerprints to afford high
      definition SERS images of the fingerprint pattern. The SERS spectra and images of
      Raman probes indirectly provide chemical information regarding the given
      proteins. By taking advantage of the high sensitivity and the capability of SERS
      technique to obtain abundant vibrational signatures of biomolecules, we have
      successfully detected minute quantities of protein present within a latent
      fingerprint. This technique provides a versatile and effective model to detect
      biomarkers within fingerprints for medical diagnostics, criminal investigation
      and other fields.

PMID- 22371040
TI  - Fabric-based exocervical and endocervical biopsy in comparison with punch biopsy
      and sharp curettage.
AB  - OBJECTIVES: Fabric-based endocervical and exocervical biopsy tools were compared
      with exocervical punch biopsy and sharp endocervical curettage. We compared the
      level of pain reported by the patient and the amount of bleeding rated by the
      physician relative to the type of biopsy used. MATERIALS AND METHODS: This was a
      2-center institutional review board-approved study of patients undergoing
      colposcopy. One center randomized patients to undergo either conventional (punch
      biopsy, sharp endocervical curettage) or fabric-based biopsy of the endocervix
      and exocervix, and a second center enrolled nonrandomized controls. The patient
      and physician subjectively rated bleeding (exocervical) and pain (endocervical
      and exocervical) from the biopsy procedure(s), which were compared using the
      nonparametric Wilcoxon test. RESULTS: Exocervical and endocervical biopsies from
      55 patients were compared. Fabric-based biopsies were abundant full-thickness
      curettage and showed statistically significant less pain and bleeding than the
      conventional biopsy methods (p < .0001). CONCLUSIONS: Fabric-based biopsies are
      significantly less traumatic than conventional biopsies. The benefits of a less
      invasive biopsy could increase the willingness to perform multiple biopsies,
      increase disease detection, and improve patient satisfaction, which could impact
      future gynecologic health-seeking behavior and compliance with colposcopy recall.

PMID- 22371041
TI  - Burden of human papillomavirus-related cervical disease in the extended middle
      East and north Africa-a comprehensive literature review.
AB  - OBJECTIVE: This study aimed to analyze the burden of human papillomavirus (HPV)
      in the Extended Middle East and North Africa (EMENA) region and to discuss the
      potential impact on HPV-related diseases derived from changing sexual behaviors
      and perceptions. MATERIALS AND METHODS: A comprehensive retrospective review of
      the available epidemiological data (publications in the past 30 years until
      January 2011) on HPV and its related diseases (especially as they relate to the
      cervix) in the EMENA region was carried out. RESULTS: Analysis of the burden of
      HPV in the EMENA region highlights an unexpectedly high prevalence of HPV, with
      rates of HPV ranging from 0% to 25% in low-risk women with normal cytology and up
      to 98% in those with genital warts and preinvasive and invasive lesions. In
      addition, cervical cancer screening practices are, at best, opportunistic in most
      countries of the region; therefore, the observed change in social and sexual
      behavior in the EMENA population, particularly in youths, could lead to an
      increase in HPV and its related diseases especially cervical cancer. CONCLUSIONS:
      This article emphasizes the need for the introduction and standardization of
      screening practices in the region. Moreover, surveillance studies are needed to
      enable the identification of HPV type distribution and to determine the potential
      impact of the introduction of HPV vaccines. These socio-epidemiological data are
      of marked value to health care decision and policymakers in prioritizing
      available public health interventions.

PMID- 22371042
TI  - Correlation of Atopobium vaginae Amount With Bacterial Vaginosis Markers.
AB  - OBJECTIVE: The purpose of this study was to test the correlation of the amount of
      Atopobium vaginae with the most commonly used markers for bacterial vaginosis
      (BV). MATERIALS AND METHODS: We enrolled 103 nonpregnant and premenopausal women
      that were positive for BV by Amsel criteria and with a Nugent score higher than
      3. All women were negative for yeast, Chlamydia trachomatis, Trichomonas
      vaginalis, and Neisseria gonorrhoeae. A. vaginae concentration was determined by
      quantitative polymerase chain reaction from samples of vaginal rinsings with 2 mL
      of sterile saline. RESULTS: There was no difference in the median values of A.
      vaginae concentration when comparing samples with presence or absence of each
      individual Amsel criterion. In the case of a higher pH cutoff value of 4.9,
      greater amounts of this microorganism (p = .02) were found. In addition,
      correlation tests showed that A. vaginae concentration is positively correlated
      with pH (p < .001) and with Nugent scores (p = .003). CONCLUSIONS: The
      quantification of A. vaginae is useful for identification of the most severe
      cases of BV.

PMID- 22371043
TI  - Promoter hypermethylation of death-associated protein kinase and p16 genes in
      vulvar lichen sclerosus.
AB  - OBJECTIVE: The purpose of this study was to discuss our investigation of the
      hypermethylation of promoter regions of tumor suppressor genes, such as death
      associated protein kinase (DAPK) and p16, in vulvar lichen sclerosus (LS), in
      comparison with a control group. MATERIALS AND METHODS: Promoter hypermethylation
      of DAPK and p16 was investigated using 24 vulvar biopsies of patients with LS who
      had received no previous treatment. The control group was composed of 15 patients
      with no vulvar disease. The DNA of subjects was treated with sodium bisulphate,
      and the genes under study were subjected to methylation-specific polymerase chain
      reaction. The resulting polymerase chain reaction products were amplified and
      analyzed using a 10% polyacrylamide gel. RESULTS: The mean age of the patients
      with LS was 57 years (the majority were postmenopausal). In the control group,
      the mean age of the patients was 50 years (p = .151). Methylation of the promoter
      region of DAPK was found in 4 (17%) of the 23 patients analyzed, and p16 promoter
      region methylation was found in 8 patients (35%). Two cases of methylation of the
      DAPK gene were also found to be methylated for the p16 gene. In the control
      group, no methylation was found in the patients analyzed for the DAPK gene and
      methylation was found in 3 (21%) of the 14 patients analyzed for the p16 gene (p
      = .190 and p = .316, respectively). CONCLUSIONS: Methylation of the DAPK and p16
      genes, although not sufficient to dictate prognosis of the disease, should not be
      underestimated because it may form part of a process of genetic and epigenetic
      alterations that in the future could become relevant to malignant transformation.

PMID- 22371044
TI  - Angiomyofibroblastoma of the vulva:  a case report of a pedunculated variant and
      review of the literature.
AB  - OBJECTIVE: Angiomyofibroblastoma (AMF) is a benign mesenchymal tumor usually
      found in the vulva. We reviewed 70 cases of vulvar AMF that have been reported in
      the English-language literature and report 1 case of a pedunculated variant. Our
      case brings the total reported to 71 and is only the fourth pedunculated variant
      reported. METHODS: This 50-year-old woman presented to our gynecology clinic with
      a 1-year history of a left labial mass. It began as pea-sized, and rapidly grew
      to 12 cm in diameter. Physical examination demonstrated a 12-cm pedunculated soft
      mass arising from the left labia majora. The clinical diagnosis was aggressive
      angiomyxoma, and a simple excision was performed. The final pathology
      demonstrated AMF. The patient remains free from tumor at 4 years of follow-up.
      RESULTS: Seventy-one cases were summarized. The mean age at presentation was 45
      years. The lesions were equally distributed between the left (52%) and right
      (48%). The most common clinical diagnosis was a Bartholin gland cyst (46%) or
      lipoma (15%). The mean duration of the lesion before seeking treatment was 29
      months, and the mean diameter at presentation was 5.9 cm. All of the patients
      were treated with simple excision. The mean duration of follow-up was 37 months.
      There was 1 report of sarcomatous transformation 2 years after initial treatment.
      CONCLUSIONS: Angiomyofibroblastoma is a rare benign tumor that most often occurs
      in the vulva. Differential diagnosis may include aggressive angiomyxoma,
      Bartholin cyst, or lipoma. The treatment of choice is simple total excision,
      which is usually curative.

PMID- 22371045
TI  - Gastrointestinal stromal tumor arising in the rectovaginal septum.
AB  - OBJECTIVE: To describe a rare case of gastrointestinal stromal tumor (GIST)
      outside the gastrointestinal tract and arising in the rectovaginal septum with
      literature review. CASE: This study involved a 29-year-old woman, gravida 0, with
      a GIST presenting as an asymptomatic tumor in the rectovaginal septum. The tumor
      was excised locally, and the patient received imatinib as adjuvant therapy. She
      is free of disease 2 years after surgery. CONCLUSIONS: To our knowledge, only 5
      cases of GIST presenting as rectovaginal mass have been reported previously.
      Local excision is the definitive treatment and the use of imatinib shows
      promising results. Mitotic activity, cellularity, and necrosis are the main
      prognostic factors. Long-term follow-up is necessary.Different physicians
      involved in the evaluation of a mass arising in the rectovaginal septum should be
      alert of GIST as differential diagnosis, even in young women.

PMID- 22371046
TI  - Autism recurrence in half siblings: strong support for genetic mechanisms of
      transmission in ASD.

PMID- 22371047
TI  - Dysfunctional astrocytic regulation of glutamate transmission in a rat model of
      depression.
AB  - Depression is usually associated with alterations in the monoaminergic system.
      However, new evidences suggest the involvement of the glutamatergic system in the
      aetiology of depression. Here we explored the glutamatergic system in a rat model
      of depression (i.e., the flinders sensitive line (FSL)) to reveal the mechanism
      underlying the emotional and cognitive aspects associated with the disease. We
      showed a dramatically elevated level of baseline glutamatergic synaptic
      transmission by whole-cell recordings as well as impairment in long-term
      potentiation induced by high-frequency stimulation in hippocampal slices from FSL
      rats compared with Sprague-Dawley rats. At behavioural level, FSL rats displayed
      recognition memory impairment in the novel object recognition test.
      Enantioselective chromatography analysis revealed lower levels of D-serine in the
      hippocampus of FSL rats and both synaptic plasticity and memory impairments were
      restored by administration of D-serine. We also observed dysfunctional astrocytic
      glutamate regulation including downregulation of the glia glutamate transporter
      GLAST as shown by western blot. One possibility is that the dysfunctional
      astrocytic glutamate reuptake triggers a succession of events, including the
      reduction of D-serine production as a safety mechanism to avoid NMDA receptor
      overactivation, which in turn causes the synaptic plasticity and memory
      impairments observed. These findings open up new brain targets for the
      development of more potent and efficient antidepressant drugs.

PMID- 22371048
TI  - Adenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and
      restores corticosterone circadian oscillation.
AB  - Maternal separation (MS) is an early life stress model that induces permanent
      changes in the central nervous system, impairing hippocampal long-term
      potentiation (LTP) and spatial working memory. There are compelling evidences for
      a role of hippocampal adenosine A(2A) receptors in stress-induced modifications
      related to cognition, thus opening a potential window for therapeutic
      intervention. Here, we submitted rats to MS and evaluated the long-lasting
      molecular, electrophysiological and behavioral impairments in adulthood. We then
      assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in
      stress-impaired animals. We report that the blockade of A(2A) receptors was
      efficient in reverting the behavior, electrophysiological and morphological
      impairments induced by MS. In addition, this effect is associated with
      restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as
      both the plasma corticosterone levels and hippocampal glucocorticoid receptor
      expression pattern returned to physiological-like status after the treatment.
      These results reveal the involvement of A(2A) receptors in the stress-associated
      impairments and directly in the stress response system by showing that the
      dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral
      effects of MS can be reverted by targeting adenosine A(2A) receptors. These
      findings provide a novel evidence for the use of adenosine A(2A) receptor
      antagonists as potential therapy against psychopathologies.

PMID- 22371049
TI  - UEMS/EBNM endeavour.

PMID- 22371050
TI  - Syllabus for Postgraduate Specialization in Nuclear Medicine--2011/2012 Update:
      nuclear medicine training in the European Union.

PMID- 22371051
TI  - Development of solid self-emulsifying drug delivery system (SEDDS) I: use of
      poloxamer 188 as both solidifying and emulsifying agent for lipids.
AB  - PURPOSE: To develop solid self-emulsifying drug delivery systems (SEDDS) for
      lipids using poloxamer 188 as both solidifying and emulsifying agents. METHODS:
      Mixtures of various lipids with poloxamer 188 and PEG 8000 were prepared at ~75
      degrees C. The molten mixtures, with and without dissolved drugs (fenofibrate and
      probucol), were then cooled to room temperature. When solids formed, they were
      characterized by powder XRD, DSC, microscopy using cross-polarization and
      confocal fluorescence techniques, dispersion test in water and particle size
      analysis of dispersions. RESULTS: When mixed with poloxamer 188 or PEG 8000,
      lipids consisting of monoesters of fatty acids with glycerol or propylene glycol
      formed solid systems, but not di- and tri-esters, which showed phase separation.
      Added to water, the solid systems containing poloxamer 188 started to disperse in
      water forming oil globules of 200-600 nm. No emulsification of lipids was
      observed from solids containing PEG 8000, indicating that the surfactant property
      of poloxamer 188 was responsible for emulsification. Powder XRD, DSC and
      microscopic examination revealed that poloxamer 188 and PEG 8000 maintained their
      crystallinity in solid systems, while the lipids were interspersed in between
      crystalline regions. The drug remained solubilized in the lipid phase.
      CONCLUSIONS: A novel solid SEDDS is developed where the drug can be solubilized
      in liquid lipids and then the lipidic solution can be converted to solid mass by
      dispersing into the microstructure of poloxamer 188.

PMID- 22371052
TI  - S-to-alphaC radical migration in the radical cations of Gly-Cys and Cys-Gly.
AB  - The radical cations of Cys-Gly and Gly-Cys were studied using ion-molecule
      reactions (IMR), infrared multiple-photon dissociation (IRMPD) spectroscopy, and
      density functional theory (DFT) calculations. Homolytic cleavage of the S-NO bond
      of nitrosylated precursors generated radical cations with the radical site
      initially located on the sulfur atom. Time-resolved ion-molecule reactions showed
      that radical site migration via hydrogen atom transfer (HAT) occurred much more
      quickly in Gly-Cys(*+) than in Cys-Gly(*+). IRMPD and DFT calculations indicated
      that for Gly-Cys, the radical migrated from the sulfur atom to the alpha-carbon
      of glycine, which is lower in energy than the sulfur radical (-53.5 kJ/mol). This
      migration does not occur for Cys-Gly because the glycine alpha-carbon is higher
      in energy than the sulfur radical (10.3 kJ/mol). DFT calculations showed that the
      highest energy barriers for rearrangement are 68.2 kJ/mol for Gly-Cys and 133.8
      kJ/mol for Cys-Gly, which is in agreement with both the IMR and IRMPD data and
      explains the HAT in Gly-Cys.

PMID- 22371053
TI  - Platelet-derived microparticles during and after acute coronary syndrome.
AB  - As microparticles are shedded upon platelet activation, and may be used to assess
      platelet function, we measured plasma concentrations of platelet-derived
      microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty
      one patients with ACS were investigated at admission, within 24 hours (before
      coronary angiography), and six months later. Sixty-one sex- and age-matched
      healthy controls were investigated once. PMPs were defined as particles <1.0 MUm
      in size, negative to phalloidin (labels cell-fragments), and positive to CD61.
      Exposure of phosphatidylserine (PS+), CD62P and CD142 were also measured. Plasma
      concentrations of PS+PMPs exposing CD61, CD62P and CD142 were elevated 2.5, 6.0-,
      and 5.0-fold at admission (p<0.001 for all, compared to controls; aspirin only),
      decreased significantly 24 hours later following initiation of treatment with
      clopidogrel and subcutaneous anticoagulation (p<0.001 for all), and decreased
      even further six months later (p<0.01 for all). However, PS+PMPs exposing CD62P
      or CD142 were still between 1.2-and 2.3-fold higher than in controls (p<0.001 for
      both). The pattern for PS-PMPs during and after the ACS was very similar to that
      for PS+PMPs although the numbers were approximately 1/3 lower. In conclusion, PMP
      concentrations follow the pattern of platelet activation during and after an ACS.
      Decreased concentrations are observed after initiation of antithrombotic
      treatment, but PMP exposing CD62P or CD142 are still elevated after six months.
      Flow cytometric measurements of PMP in frozen-thawed samples enable studies of
      platelet function in larger clinical trials.

PMID- 22371054
TI  - Preterm EEG: a multimodal neurophysiological protocol.
AB  - Since its introduction in early 1950s, electroencephalography (EEG) has been
      widely used in the neonatal intensive care units (NICU) for assessment and
      monitoring of brain function in preterm and term babies. Most common indications
      are the diagnosis of epileptic seizures, assessment of brain maturity, and
      recovery from hypoxic-ischemic events. EEG recording techniques and the
      understanding of neonatal EEG signals have dramatically improved, but these
      advances have been slow to penetrate through the clinical traditions. The aim of
      this presentation is to bring theory and practice of advanced EEG recording
      available for neonatal units.     In the theoretical part, we will present
      animations to illustrate how a preterm brain gives rise to spontaneous and evoked
      EEG activities, both of which are unique to this developmental phase, as well as
      crucial for a proper brain maturation. Recent animal work has shown that the
      structural brain development is clearly reflected in early EEG activity. Most
      important structures in this regard are the growing long range connections and
      the transient cortical structure, subplate. Sensory stimuli in a preterm baby
      will generate responses that are seen at a single trial level, and they have
      underpinnings in the subplate-cortex interaction. This brings neonatal EEG
      readily into a multimodal study, where EEG is not only recording cortical
      function, but it also tests subplate function via different sensory modalities.
      Finally, introduction of clinically suitable dense array EEG caps, as well as
      amplifiers capable of recording low frequencies, have disclosed multitude of
      brain activities that have as yet been overlooked.    In the practical part of
      this video, we show how a multimodal, dense array EEG study is performed in
      neonatal intensive care unit from a preterm baby in the incubator. The video
      demonstrates preparation of the baby and incubator, application of the EEG cap,
      and performance of the sensory stimulations.

PMID- 22371055
TI  - Improved methods for detection of beta-galactosidase (lacZ) activity in hard
      tissue.
AB  - The beta-galactosidase gene (lacZ) of Escherichia coli is widely used as a
      reporter gene. The expression of lacZ can be detected by enzyme-based
      histochemical staining using chromogenic substrates such as 5-bromo-4-chloro-3
      indolyl-beta-D: -galactoside (X-gal). Because the enzymatic activity of lacZ is
      vulnerable to high temperatures and acid treatment for demineralization,
      detection of lacZ on paraffinized sections is difficult, especially for hard
      tissues, which require demineralization before sectioning in paraffin. To
      circumvent this problem, whole-mount X-gal staining before sectioning is
      performed. However, detection of lacZ activity in the center of larger portions
      of hard whole adult tissues is challenging. In this study, focusing on fixation
      procedures, we determined the conditions conducive to improved detection of lacZ
      activity in deeper areas of whole tissues. We used an annexin a5 (Anxa5)-lacZ
      reporter mouse model in which the Anxa5 expression in hard tissue is indicated by
      lacZ activity. We found that lacZ activity could be detected throughout the
      periodontal ligament of adult mice when fixed in 100% acetone, whereas it was not
      detected in the periodontal ligament around the root apex fixed in glutaraldehyde
      and paraformaldehyde. This staining could not be detected in wild-type mice.
      Acetone maintains the lacZ activity within 48 h of fixation at both 4 degrees C
      and at room temperature. In conclusion, acetone is the optimal fixative to
      improve permeability for staining of lacZ activity in large volumes of adult hard
      tissues.

PMID- 22371056
TI  - Cell cycle-dependent subcellular distribution of ClC-3 in HeLa cells.
AB  - Chloride channel-3 (ClC-3) is suggested to be a component and/or a regulator of
      the volume-activated Cl(-) channel in the plasma membrane. However, ClC-3 is
      predominantly located inside cells and the role of intracellular ClC-3 in tumor
      growth is unknown. In this study, we found that the subcellular distribution of
      endogenous ClC-3 varied in a cell cycle-dependent manner in HeLa cells. During
      interphase, ClC-3 was distributed throughout the cell and it accumulated at
      various positions in different stages. In early G1, ClC-3 was mainly located in
      the nucleus. In middle G1, ClC-3 gathered around the nuclear periphery as a ring.
      In late G1, ClC-3 moved back into the nucleus, where it remained throughout S
      phase. In G2, ClC-3 was concentrated in the cytoplasm. When cells progressed from
      G2 to the prophase of mitosis, ClC-3 from the cytoplasm translocated into the
      nucleus. During metaphase and anaphase, ClC-3 was distributed throughout the cell
      except for around the chromosomes and was aggregated at the spindle poles and in
      between two chromosomes, respectively. ClC-3 was then again concentrated in the
      nucleus upon the progression from telophase to cytokinesis. These results reveal
      a cell cycle-dependent change of the subcellular distribution of ClC-3 and
      strongly suggest that ClC-3 has nucleocytoplasmic shuttling dynamics that may
      play key regulatory roles during different stages of the cell cycle in tumor
      cells.

PMID- 22371057
TI  - The impact of aging on work disability and return to work: insights from workers'
      compensation claim records.
AB  - OBJECTIVE: To assess the impact of an aging workforce on (1) the incidence of
      work-related injury or disease and (2) the return-to-work (RTW) process. METHODS:
      Workers' compensation claims (from 2001 to 2004) from Victoria, Australia (n =
      59,525) were analyzed. Time off work was defined in terms of time until first
      RTW, number of workdays compensated, and work disability recurrences. RESULTS:
      The incidence of lost-time claims was 7.54 per 1000 worker-years; incidence
      increased with age to reach a maximum at ages 50 to 54 years. Days until first
      return also increased with age, as did the sum of compensated days. Recurrences
      were common (37%) and also increased with age. CONCLUSIONS: The aging workforce
      will lead to substantial increase in work disability. Besides general disease and
      injury preventative practices, policies could aim to provide tailored RTW
      programs for aging workers.

PMID- 22371058
TI  - Risk factors for subclinical atherosclerosis in firefighters.
AB  - OBJECTIVE: Heart disease is the leading cause of firefighter line-of-duty deaths.
      The study objectives were to identify early atherosclerotic disease through
      ultrasound measurement of carotid intima-media thickness (CIMT) and risk factors
      predicting increased CIMT and carotid plaque. METHODS: Following ultrasound
      evaluation of 597 Phoenix and Tucson firefighters, logistic regression was used
      to identify risk factors for mean CIMT greater than 75th percentile and for
      carotid plaque. RESULTS: Age, low-density lipoprotein cholesterol (LDL-C) of 100
      mg/dL or more, and high-density lipoprotein cholesterol were significant
      independent predictors of increased CIMT. Age, hypertension, LDL-C, and plasma
      soluble P-selectin were significant predictors of carotid plaque. CONCLUSIONS:
      This study supports an emphasis on traditional risk factors for atherosclerotic
      disease in firefighters, in particular maintaining LDL-C less than 100 mg/dL.
      Plasma soluble P-selectin may help identify firefighters at increased risk for
      carotid plaque.

PMID- 22371059
TI  - Substantiating the concept of work strain: its implication for the assessment of
      work stressors.
AB  - OBJECTIVE: To assess which work stressors are substantially contributing to work
      strain and examine their relative contribution. METHODS: We prospectively
      examined the association between work stressors and work strain, which was
      defined as employees reporting ill due to work stress. Relevant work stressors
      were combined into a stressor score with each stressor having its own relevance.
      Standardized odds ratios (SORs) were calculated using logistic regression
      analysis and used to compare the associations obtained between already existing
      scales and the stressor score with work strain. RESULTS: The stressor score
      yielded an SOR of 1.89 (95% confidence interval: 1.49 to 2.41) for work strain,
      while psychological demands (JCQ) yielded an SOR of 1.46 (95% confidence
      interval: 1.09 to 1.88) for work strain. CONCLUSIONS: We were able to extend and
      substantiate the range of relevant work stressors into a more comprehensive
      measure, which should be used to optimize prevention strategies.

PMID- 22371060
TI  - Cost-effectiveness of a workplace-based incentivized weight loss program.
AB  - OBJECTIVE: To evaluate the cost-effectiveness ratios of a nursing home-based
      incentivized Behavioral Weight Management Program (BWMP) from the employer's
      perspective. METHODS: Seventy-two overweight and obese health care workers
      completed the BWMP (n = 35 incentivized; n = 37 nonincentivized). Weight change
      outcomes were compared for the pre- (0) and postintervention (28 weeks) follow-up
      periods within and between sites. Comprehensive estimates of BWMP direct program
      costs and avoided costs of absenteeism and productivity improvements were
      estimated to evaluate a business case. RESULTS: There was a significant
      difference (P = 0.01) between the average per-participant weight change between
      incentivized sites (-7.4 lb) and nonincentivized sites (-2.2 lb). The cost
      effectiveness ratios per pound of weight loss were $25.5 and $58.1, respectively.
      CONCLUSIONS: In general, incentivized BWMPs were more cost effective. To generate
      a business case, enhancement in productivity becomes a critical factor and future
      research needs to investigate it further.

PMID- 22371061
TI  - Single-step purification and immobilization of MBP-phytase fusion on starch agar
      beads: application in dephytination of soy milk.
AB  - Periplasmic phytase, appA from E. coli has been noticed as a superior feed and
      food additive owing to its high specific activity, acidic pH optimum and
      resistance to gastric proteases. E. coli phytase was expressed as a fusion
      protein with maltose-binding protein, affinity-purified to homogeneity and,
      subsequently, immobilized in one step using a cost-effective matrix prepared from
      starch agar bead. Immobilized enzyme revealed an activity optimum at pH 6, while
      that of free enzyme was observed at pH 4. Both the immobilized and free enzyme
      showed a temperature optimum at 60  degrees C. Cleavage of 87 kDa fusion protein
      using factor Xa released 45 kDa appA. Hydrolysis of soy milk using immobilized
      enzyme led to 10% increase in release of inorganic phosphate at 50  degrees C
      relative to free fusion protein. This study suggests the usability of MBP as an
      immobilizing linker to other food enzymes for economical use in industry.

PMID- 22371062
TI  - Laccase production by the aquatic ascomycete Phoma sp. UHH 5-1-03 and the white
      rot basidiomycete Pleurotus ostreatus DSM 1833 during submerged cultivation on
      banana peels and enzyme applicability for the removal of endocrine-disrupting
      chemicals.
AB  - This work aimed to study the production of laccase from Pleurotus ostreatus DSM
      1833 and Phoma sp. UHH 5-1-03 using banana peels as alternative carbon source,
      the subsequent partial purification and characterization of the enzyme, as well
      the applicability to degrade endocrine disruptors. The laccase stability with pH
      and temperature, the optimum pH, the K (m) and V(max) parameters, and the molar
      mass were determined. Tests were conducted for assessing the ability of
      degradation of the endocrine disruptors t-nonylphenol, bisphenol A, and 17alpha
      ethinylestradiol. Laccase production of 752 and 1,117 U L-1 was obtained for
      Phoma sp. and P. ostreatus, respectively. Phoma sp. laccase showed higher
      stability with temperature and pH. The laccase from both species showed higher
      affinity by syringaldazine. The culture broth with banana peels induced the
      production of two isoforms of P. ostreatus (58.7 and 21 kDa) and one of Phoma sp.
      laccase (72 kDa). In the first day of incubation, the concentrations of bisphenol
      A and 17alpha-ethinylestradiol were reduced to values close to zero and after 3
      days the concentration of t-nonylphenol was reduced in 90% by the P. ostreatus
      laccase, but there was no reduction in its concentration by the Phoma sp.
      laccase.

PMID- 22371063
TI  - A potential commercial source of fucoxanthin extracted from the microalga
      Phaeodactylum tricornutum.
AB  - Fucoxanthin, one of the main marine carotenoids, is abundant in macro- and
      microalgae. Here, fucoxanthin was isolated and structurally identified as the
      major carotenoid in the diatom Phaeodactylum tricornutum through chromatographic
      and spectroscopic methods, such as liquid chromatography-positive-ion atmospheric
      pressure chemical ionization/mass spectroscopy and nuclear magnetic resonance.
      This pigment was quantified by reverse-phase high-performance liquid
      chromatography, and a number of extraction procedures were assessed to
      investigate the effect of solvent type, extraction time, temperature, and
      extraction method (maceration, ultrasound-assisted extraction, Soxhlet
      extraction, and pressurized liquid extraction). Among the investigated solvents,
      ethanol provided the best fucoxanthin extraction yield (15.71 mg/g freeze-dried
      sample weight). Fucoxanthin content in the extracts produced by the different
      methods was quite constant (15.42-16.51 mg/g freeze-dried sample weight) but
      increased steeply based on the percentage of ethanol in water, emphasizing the
      importance of ethanol in the extraction. The results indicate that P. tricornutum
      is a rich source of fucoxanthin (at least ten times more abundant than that in
      macroalgae) that is easily extracted with ethanol, suggesting potential
      applications in human and animal food, health, and cosmetics.

PMID- 22371065
TI  - Intrinsic characteristics of Cr6+-resistant bacteria isolated from an
      electroplating industry polluted soils for plant growth-promoting activities.
AB  - The Cr(6+)-resistant plant growth-promoting bacteria was isolated from soil
      samples that were collected from an electroplating industry at Coimbatore, India,
      that had tolerated chromium concentrations up to 500 mg Cr(6+)/L in Luria-Bertani
      medium. Based on morphology, physiology, and biochemical characteristics, the
      strain was identified as Bacillus sp. following the Bergey's manual of
      determinative bacteriology. Evaluation of plant growth-promoting parameters has
      revealed the intrinsic ability of the strain for the production of indole-3
      acetic acid (IAA), siderophore, and solubilization of insoluble phosphate.
      Bacillus sp. have utilized tryptophan as a precursor for their growth and
      produced IAA (122 MUg/mL). Bacillus sp. also exhibited the production of
      siderophore that was tested qualitatively using Chrome Azurol S (CAS) assay
      solution and utilized the insoluble tricalcium phosphate as the sole source of
      phosphate exhibiting higher rate of phosphate solubilization after 72 h of
      incubation (1.45 MUg/mL). Extent of Cr(6+) uptake and accumulation of Cr(6+) in
      the cell wall of Bacillus sp. was investigated using atomic absorption
      spectrophotometer and scanning electron microscope-energy dispersive
      spectroscopy, respectively. The congenital capability of this Cr(6+)-resistant
      plant growth-promoting Bacillus sp. could be employed as bacterial inoculum for
      the improvement of phytoremediation in heavy metal contaminated soils.

PMID- 22371064
TI  - Pretreatment of rice straw using a butanone or an acetaldehyde dilute solution
      explosion for producing ethanol.
AB  - Ethanol conversion from rice straw using butanone and acetaldehyde dilute
      solution explosions was evaluated based on the optimization of pure water
      explosion. To decrease residual inhibitor content, the exploded slurry was dried
      and investigated at different temperature. Using a 0.9-mol/L butanone solution
      explosion, with the explosion pressure set at 3.1 MPa, the residence time at 7
      min, the dried rice straw-to-water ratio at 1:3 (w/w), and the exploded slurry
      drying temperuture at 90  degrees C for 8 h, the yields of total sugar, glucose,
      and xylose were 85%, 88%, 82% (w/w), respectively, and the ethanol productivity
      was 26.0 g/100 g rice straw dry matter. Moreover, 0.5-mol/L acetaldehyde dilute
      solution explosion improved the efficiency of enzymatic hydrolysis (EH) and
      simultaneous saccharification and co-fermentation (SSCF), and the residual
      inhibitors had negligible effects on EH and SSCF after detoxification by drying.
      The results suggested that compared with pure water explosions, the use of
      butanone and of acetaldehyde dilute solution explosions lowered the explosive
      temperature and improved the sugar yield, although relative crystallinity of the
      rice straw dry matter was increased after the explosion.

PMID- 22371066
TI  - Studies of ciprofloxacin encapsulation on alginate/pectin matrixes and its
      relationship with biodisponibility.
AB  - Screening of ciprofloxacin (Cip) with selected biopolymers brings about 90%
      antibiotic interactions with a coacervate composed of alginate/high metoxylated
      pectin in 2:1 ratio. Fourier transform infrared spectroscopy analysis provides
      information about the nature of this interaction, revealing ionic and hydrophobic
      patterns among the molecules. Alginate/high methoxylated pectin gel microspheres
      developed by ionic gelation encapsulates 46.8 +/- 5.0% Cip. The gel matrix can
      release Cip in a sustained manner, releasing 42.7 +/- 0.2% in 2 h under simulated
      stomach pH conditions, and 83.3 +/- 1.1% Cip release in 80 mM phosphate at pH =
      7.40 (intestinal). The increase of sodium chloride from 50 to 200 mM implies a
      Cip release from 69.0 +/- 1.5% to 95.1 +/- 3.6% respectively in 2 h. Scanning
      electron microscopy revealed the cohesive effect of HM pectin over alginate
      molecules on the microsphere surface. Those results guarantee all Cip contained
      in the alginate/HM pectin microspheres could be released in an established
      kinetic profile along the gastrointestinal tract, avoiding the Cip undesirable
      side effects during absorption.

PMID- 22371067
TI  - Controlled release of sulfasalazine release from "smart" pectin gel microspheres
      under physiological simulated fluids.
AB  - Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used
      mainly for the treatment of an inflammatory bowel and other diseases. Two pectins
      with different methylation degrees were blended to synthesized gel microspheres
      by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was
      found to be around of 99% in all formulations tested. However, different SLZ
      release profiles related to the methylation degrees of pectin were observed.
      Mixture of low methylated (LM) and high methylated (HM) pectins in the presence
      of calcium(II) displayed the best microsphere morphologies among the formulations
      tested determined by optical and electronic microscopies. The percentage of drug
      release using a mixture of LM and HM pectins after 255 min in simulated gastric
      fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH
      = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.

PMID- 22371068
TI  - Effect of penicillin on nitrite-oxidizing bacteria in activated sludge.
AB  - The effects of penicillin G on the number and activity of nitrite-oxidizing
      bacteria were investigated in laboratory-scale reactors and batch tests. At a
      concentration of 100 mg L(-1), addition of penicillin G for short periods did not
      significantly affect nitrite oxidation, while addition for more than 2 months
      suppressed nitrite oxidation. Fluorescence in situ hybridization with 16S
      ribosomal RNA-targeted probes revealed a slight decrease in the abundance of
      Nitrospira, while Nitrobacter was not affected by addition of penicillin G for
      more than 39 days. The resistance of nitrite-oxidizing bacteria to penicillin
      appeared to be positively affected by intermittent aeration only when accompanied
      by denitrification; otherwise, the aeration mode (continuous or intermittent
      aeration) did not significantly affect the abundance of Nitrobacter and
      Nitrospira.

PMID- 22371069
TI  - Persistence of hepatitis A vaccine induced seropositivity in infants and young
      children by maternal antibody status: 10-year follow-up.
AB  - Persistence of seropositivity conferred by hepatitis A vaccine administered to
      children <2 years of age is unknown and passively transferred maternal antibodies
      to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response
      to the vaccine. One hundred ninety-seven infants and young children were
      randomized into three groups to receive a two-dose hepatitis A vaccine: group 1
      at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months
      of age. Within each group, infants were randomized by maternal anti-HAV status.
      Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years
      after the second dose of hepatitis A vaccination. Children in all groups had
      evidence of seroprotection (>10 mIU/mL) at 1 month after the second dose. At 10
      years, all children retained seroprotective anti-HAV levels except for only 7%
      and 11% of children in group 1 born to anti-HAV-negative and anti-HAV-positive
      mothers, respectively, and 4% of group 3 children born to anti-HAV-negative
      mothers. At 10 years, children born to anti-HAV-negative mothers in group 3 had
      the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence
      interval, 71-133 mIU/mL) and children born to anti-HAV-positive mothers in group
      1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV
      levels through 10 years of age correlated with initial peak anti-HAV levels
      (tested at 1 month after the second dose). CONCLUSION: The seropositivity induced
      by hepatitis A vaccine given to children <2 years of age persists for at least 10
      years regardless of presence of maternal anti-HAV.

PMID- 22371070
TI  - Common MUTYH mutations and colorectal cancer risk in multiethnic populations.
AB  - MUTYH is associated with colorectal cancer (CRC) risk. We studied the frequency
      of MUTYH and risk of CRC in Arabs, North African and European Jews. Participants
      were all 593 Sephardi Moroccan Jews (232 cases, 361 controls) and all 631 Arabs
      (327 cases, 304 controls) recruited into a population-based study of colorectal
      cancer in Israel, as well as a random sample of 189 Ashkenazi Jewish cases. Two
      MUTYH mutations, G396D and Y179C, were studied in 1,413 individuals, with MUTYH
      sequence analysis in 46 cases with CRC in a sibling or adenoma. No carriers of
      mutations in MUTYH were identified in Ashkenazi Jews and only one in Arabs. In
      Sephardi Jews, 28 carriers of G396D, 25 (4.2%) heterozygotes and 3 (0.5%)
      homozygotes were identified. Four (0.7%) were heterozygote carriers of the Y179C
      mutation. Two compound heterozygous carriers of Y179C and G396D were identified.
      Homozygote carriers of G396D had nonsignificantly elevated risk of CRC (OR =
      11.0, 95% CI: 0.91-213.9, p = 0.06), and combined bi-allelic carriers of G396D
      and Y179C had increased risk, OR = 17.4, 95% CI = (1.9-316.7, p = 0.009). Four of
      five bi-allelic carriers reported a family history of CRC. Sequencing of 46
      colorectal cancer cases with family history and additional adenomas, did not
      identify any other non-founder mutations. MUTYH carriers of the two common
      founder mutations are profoundly under-represented among both Ashkenazi Jews and
      Arabs. The prevalence of MUTYH carriers of the common mutations is much higher in
      Sephardi Jews. Bi-allelic carriers of mutations in MUTYH, are associated with
      highly risk of colorectal cancer.

PMID- 22371071
TI  - Sexual dimorphism in skeletal browridge and chin morphologies determined using a
      new quantitative method.
AB  - Qualitative methods of describing sexual dimorphism in discrete cranial traits
      have been criticized for their subjectivity and statistical limitations. However,
      researchers have yet to be able to accurately capture the morphology of these
      individual traits using traditional metric techniques. This article presents a
      method to quantify morphological variation in the skeletal browridge and chin
      using 3D surface laser scans. Browridge and chin regions are isolated from the
      skull using objectively defined landmarks and planes. Region areas and volumes
      are used to quantify absolute and relative size, while semilandmarks along
      transects are used for more detailed morphometric analyses. An intraobserver
      error study indicates high repeatability of the method. Application of the method
      is demonstrated on a sample of US males and females of black and white
      ancestries. Results suggest significant effects of both sex and ancestry on brow
      and chin morphologies and are consistent with traditional qualitative
      descriptions. Our results indicate that the method can accurately and reliably
      quantify browridge and chin morphologies, providing a tool to objectively
      describe and statistically analyze these traditionally qualitative discrete
      cranial traits.

PMID- 22371072
TI  - Micro-/nano- sized hydroxyapatite directs differentiation of rat bone marrow
      derived mesenchymal stem cells towards an osteoblast lineage.
AB  - Regenerative medicine consisting of cells and materials provides a new way for
      the repair and regeneration of tissues and organs. Nano-biomaterials are
      highlighted due to their advantageous features compared with conventional micro
      materials. The aim of this study is to investigate the effects of micro-/nano-
      sized hydroxyapatite (MU/n-HA) on the osteogenic differentiation of rat bone
      marrow derived mesenchymal stem cells (rBMSCs). MU/n-HA were prepared by a
      microwave synthesizer and precipitation method, respectively. Different sizes of
      MU/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It
      was shown that rBMSCs expressed higher levels of osteoblast-related markers by n
      HA than MU-HA stimulation. The size of HA is an important factor for affecting
      the osteogenic differentiation of rBMSCs. This provides a new avenue for
      mechanistic studies of stem cell differentiation and a new approach to obtain
      more committed differentiated cells.

PMID- 22371073
TI  - A new pharmacological agent (AKB-4924) stabilizes hypoxia inducible factor-1 (HIF
      1) and increases skin innate defenses against bacterial infection.
AB  - Hypoxia inducible factor-1 (HIF-1) is a transcription factor that is a major
      regulator of energy homeostasis and cellular adaptation to low oxygen stress. HIF
      1 is also activated in response to bacterial pathogens and supports the innate
      immune response of both phagocytes and keratinocytes. In this work, we show that
      a new pharmacological compound AKB-4924 increases HIF-1 levels and enhances the
      antibacterial activity of phagocytes and keratinocytes against both methicillin
      sensitive and methicillin-resistant strains of Staphylococcus aureus in vitro.
      AKB-4924 is also effective in stimulating the killing capacity of keratinocytes
      against the important opportunistic skin pathogens Pseudomonas aeruginosa and
      Acinetobacter baumanii. The effect of AKB-4924 is mediated through the activity
      of host cells, as the compound exerts no direct antimicrobial activity.
      Administered locally as a single agent, AKB-4924 limits S. aureus proliferation
      and lesion formation in a mouse skin abscess model. This approach to
      pharmacologically boost the innate immune response via HIF-1 stabilization may
      serve as a useful adjunctive treatment for antibiotic-resistant bacterial
      infections.

PMID- 22371075
TI  - Metabolic cartography: experimental quantification of metabolic fluxes from
      isotopic labelling studies.
AB  - For the past decade, flux maps have provided researchers with an in-depth
      perspective on plant metabolism. As a rapidly developing field, significant
      headway has been made recently in computation, experimentation, and overall
      understanding of metabolic flux analysis. These advances are particularly
      applicable to the study of plant metabolism. New dynamic computational methods
      such as non-stationary metabolic flux analysis are finding their place in the
      toolbox of metabolic engineering, allowing more organisms to be studied and
      decreasing the time necessary for experimentation, thereby opening new avenues by
      which to explore the vast diversity of plant metabolism. Also, improved methods
      of metabolite detection and measurement have been developed, enabling
      increasingly greater resolution of flux measurements and the analysis of a
      greater number of the multitude of plant metabolic pathways. Methods to
      deconvolute organelle-specific metabolism are employed with increasing
      effectiveness, elucidating the compartmental specificity inherent in plant
      metabolism. Advances in metabolite measurements have also enabled new types of
      experiments, such as the calculation of metabolic fluxes based on (13)CO(2)
      dynamic labelling data, and will continue to direct plant metabolic engineering.
      Newly calculated metabolic flux maps reveal surprising and useful information
      about plant metabolism, guiding future genetic engineering of crops to higher
      yields. Due to the significant level of complexity in plants, these methods in
      combination with other systems biology measurements are necessary to guide plant
      metabolic engineering in the future.

PMID- 22371074
TI  - Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative
      and nitrative stress, and cell death during remote neurodegeneration.
AB  - Remote neuronal degeneration and death/injury, which often occur in regions
      remote but functionally connected to the primary lesion site, may play a pivotal
      role in extending neuronal damage/dysfunction following traumatic brain injury,
      stroke, or peripheral nerve injury, as well as in chronic neurodegenerative
      diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even
      though the precise mechanisms of remote neuronal injury are poorly understood and
      no efficacious treatment options are available, it involves glial activation,
      inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly
      discovered endocannabinoid signaling system consisting of endocannabinoids
      (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes,
      and their primary G protein-coupled cannabinoid 1 and 2 (CB(1) and CB(2))
      receptors has been implicated in the regulation of numerous physiological and
      pathological processes/functions, including those associated with
      neurodegeneration. Using a well-characterized rodent model of remote neuronal
      degeneration, Oddi et al. (J Mol Med 2012, in press, DOI 10.1007/s00109-012-0884
      1 ) have demonstrated that targeting CB(2) cannabinoid receptors may represent a
      promising novel approach to attenuate this pathological process. This editorial
      discusses the clinical significance of these interesting observations and the
      mechanisms of the possible interplay of CB(2) receptors with nitric oxide
      synthases, oxidative and nitrative stress, and cell death during remote
      neurodegeneration.

PMID- 22371076
TI  - An evolutionarily conserved mitochondrial orf108 is associated with cytoplasmic
      male sterility in different alloplasmic lines of Brassica juncea and induces male
      sterility in transgenic Arabidopsis thaliana.
AB  - Nuclear-mitochondrial gene interactions governing cytoplasmic male sterility
      (CMS) in angiosperms have been found to be unique to each system. Fertility
      restoration of three diverse alloplasmic CMS lines of Brassica juncea by a line
      carrying the fertility-restorer gene introgressed from Moricandia arvensis
      prompted this investigation to examine the molecular basis of CMS in these lines.
      Since previous studies had found altered atpA transcription associated with CMS
      in these lines, the atpA genes and transcripts of CMS, fertility-restored, and
      euplasmic lines were cloned and compared. atpA coding and downstream sequences
      were conserved among CMS and euplasmic lines but major differences were found in
      the 5' flanking sequences of atpA. A unique open reading frame (ORF), orf108, co
      transcribed with atpA, was found in male sterile flowers of CMS lines carrying
      mitochondrial genomes of Diplotaxis berthautii, D. catholica, or D. erucoides. In
      presence of the restorer gene, the bicistronic orf108-atpA transcript was cleaved
      within orf108 to yield a monocistronic atpA transcript. Transgenic expression of
      orf108 with anther-specific Atprx18 promoter in Arabidopsis thaliana gave 50%
      pollen sterility, indicating that Orf108 is lethal at the gametophytic stage.
      Further, lack of transmission of orf108 to the progeny showed for the first time
      that mitochondrial ORFs could also cause female sterility. orf108 was found to be
      widely distributed among wild relatives of Brassica, indicating its ancient
      origin. This is the first report that shows that CMS lines of different origin
      and morphology could share common molecular basis. The gametic lethality of
      Orf108 offers a novel opportunity for transgene containment.

PMID- 22371078
TI  - S-Nitrosoglutathione is a component of wound- and salicylic acid-induced systemic
      responses in Arabidopsis thaliana.
AB  - S-Nitrosoglutathione (GSNO) is a bioactive, stable, and mobile reservoir of
      nitric oxide (NO), and an important player in defence responses to herbivory and
      pathogen attack in plants. It has been demonstrated previously that GSNO
      reductase (GSNOR) is the main enzyme responsible for the in vivo control of
      intracellular levels of GSNO. In this study, the role of S-nitrosothiols, in
      particular of GSNO, in systemic defence responses in Arabidopsis thaliana was
      investigated further. It was shown that GSNO levels increased rapidly and
      uniformly in injured Arabidopsis leaves, whereas in systemic leaves GSNO was
      first detected in vascular tissues and later spread over the parenchyma,
      suggesting that GSNO is involved in the transmission of the wound mobile signal
      through the vascular tissue. Moreover, GSNO accumulation was required to activate
      the jasmonic acid (JA)-dependent wound responses, whereas the alternative JA
      independent wound-signalling pathway did not involve GSNO. Furthermore, extending
      previous work on the role of GSNOR in pathogenesis, it was shown that GSNO acts
      synergistically with salicylic acid in systemic acquired resistance activation.
      In conclusion, GSNOR appears to be a key regulator of systemic defence responses,
      in both wounding and pathogenesis.

PMID- 22371077
TI  - Physiological and molecular analysis of the interaction between aluminium
      toxicity and drought stress in common bean (Phaseolus vulgaris).
AB  - Aluminium (Al) toxicity and drought are two major factors limiting common bean
      (Phaseolus vulgaris) production in the tropics. Short-term effects of Al toxicity
      and drought stress on root growth in acid, Al-toxic soil were studied, with
      special emphasis on Al-drought interaction in the root apex. Root elongation was
      inhibited by both Al and drought. Combined stresses resulted in a more severe
      inhibition of root elongation than either stress alone. This result was different
      from the alleviation of Al toxicity by osmotic stress (-0.60 MPa polyethylene
      glycol) in hydroponics. However, drought reduced the impact of Al on the root
      tip, as indicated by the reduction of Al-induced callose formation and MATE
      expression. Combined Al and drought stress enhanced up-regulation of ACCO
      expression and synthesis of zeatin riboside, reduced drought-enhanced abscisic
      acid (ABA) concentration, and expression of NCED involved in ABA biosynthesis and
      the transcription factors bZIP and MYB, thus affecting the regulation of ABA
      dependent genes (SUS, PvLEA18, KS-DHN, and LTP) in root tips. The results provide
      circumstantial evidence that in soil, drought alleviates Al injury, but Al
      renders the root apex more drought-sensitive, particularly by impacting the gene
      regulatory network involved in ABA signal transduction and cross-talk with other
      phytohormones necessary for maintaining root growth under drought.

PMID- 22371079
TI  - Towards mechanistic models of plant organ growth.
AB  - Modelling and simulation are increasingly used as tools in the study of plant
      growth and developmental processes. By formulating experimentally obtained
      knowledge as a system of interacting mathematical equations, it becomes feasible
      for biologists to gain a mechanistic understanding of the complex behaviour of
      biological systems. In this review, the modelling tools that are currently
      available and the progress that has been made to model plant development, based
      on experimental knowledge, are described. In terms of implementation, it is
      argued that, for the modelling of plant organ growth, the cellular level should
      form the cornerstone. It integrates the output of molecular regulatory networks
      to two processes, cell division and cell expansion, that drive growth and
      development of the organ. In turn, these cellular processes are controlled at the
      molecular level by hormone signalling. Therefore, combining a cellular modelling
      framework with regulatory modules for the regulation of cell division, expansion,
      and hormone signalling could form the basis of a functional organ growth
      simulation model. The current state of progress towards this aim is that the
      regulation of the cell cycle and hormone transport have been modelled extensively
      and these modules could be integrated. However, much less progress has been made
      on the modelling of cell expansion, which urgently needs to be addressed. A
      limitation of the current generation models is that they are largely qualitative.
      The possibilities to characterize existing and future models more quantitatively
      will be discussed. Together with experimental methods to measure crucial model
      parameters, these modelling techniques provide a basis to develop a Systems
      Biology approach to gain a fundamental insight into the relationship between gene
      function and whole organ behaviour.

PMID- 22371080
TI  - Fluxes in central carbohydrate metabolism of source leaves in a fructan-storing
      C3 grass: rapid turnover and futile cycling of sucrose in continuous light under
      contrasted nitrogen nutrition status.
AB  - This work assessed the central carbohydrate metabolism of actively
      photosynthesizing leaf blades of a C3 grass (Lolium perenne L.). The study used
      dynamic (13)C labelling of plants growing in continuous light with contrasting
      supplies of nitrogen ('low N' and 'high N') and mathematical analysis of the
      tracer data with a four-pool compartmental model to estimate rates of: (i)
      sucrose synthesis from current assimilation; (ii) sucrose export/use; (iii)
      sucrose hydrolysis (to glucose and fructose) and resynthesis; and (iv) fructan
      synthesis and sucrose resynthesis from fructan metabolism. The contents of
      sucrose, fructan, glucose, and fructose were almost constant in both treatments.
      Labelling demonstrated that all carbohydrate pools were turned over. This
      indicated a system in metabolic steady state with equal rates of synthesis and
      degradation/consumption of the individual pools. Fructan content was enhanced by
      nitrogen deficiency (55 and 26% of dry mass at low and high N, respectively).
      Sucrose content was lower in nitrogen-deficient leaves (2.7 versus 6.7%). Glucose
      and fructose contents were always low (<1.5%). Interconversions between sucrose,
      glucose, and fructose were rapid (with half-lives of individual pools ranging
      between 0.3 and 0.8 h). Futile cycling of sucrose through sucrose hydrolysis (67
      and 56% of sucrose at low and high N, respectively) and fructan metabolism (19
      and 20%, respectively) was substantial but seemed to have no detrimental effect
      on the relative growth rate and carbon-use efficiency of these plants. The main
      effect of nitrogen deficiency on carbohydrate metabolism was to increase the half
      life of the fructan pool from 27 to 62 h and to effectively double its size.

PMID- 22371081
TI  - Massively parallel functional dissection of mammalian enhancers in vivo.
AB  - The functional consequences of genetic variation in mammalian regulatory elements
      are poorly understood. We report the in vivo dissection of three mammalian
      enhancers at single-nucleotide resolution through a massively parallel reporter
      assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes
      with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a
      unique sequence tag embedded within a transcriptional cassette. We introduced
      each enhancer library into mouse liver and measured the relative activities of
      individual haplotypes en masse by sequencing the transcribed tags. Linear
      regression analysis yielded highly reproducible estimates of the effect of every
      possible single-nucleotide change on enhancer activity. The functional
      consequence of most mutations was modest, with ~22% affecting activity by >1.2
      fold and ~3% by >2-fold. Several, but not all, positions with higher effects
      showed evidence for purifying selection, or co-localized with known liver
      associated transcription factor binding sites, demonstrating the value of
      empirical high-resolution functional analysis.

PMID- 22371082
TI  - Tracking the progression of the human inner cell mass during embryonic stem cell
      derivation.
AB  - The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro
      have been shown to correspond to stages of mouse embryonic development. For human
      cells, little is known about the events that precede the generation of ESCs or
      whether they correlate with in vivo developmental stages. Here we investigate the
      cellular and molecular changes that occur during the transition from the human
      inner cell mass (ICM) to ESCs in vitro. We demonstrate that human ESCs originate
      from a post-ICM intermediate (PICMI), a transient epiblast-like structure that
      has undergone X-inactivation in female cells and is both necessary and sufficient
      for ESC derivation. The PICMI is the result of progressive and defined ICM
      organization in vitro and has a distinct state of cell signaling. The PICMI can
      be cryopreserved without compromising ESC derivation capacity. As a closer
      progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent
      state of human stem cells.

PMID- 22371083
TI  - Functional beta-cell maturation is marked by an increased glucose threshold and
      by expression of urocortin 3.
AB  - Insulin-expressing cells that have been differentiated from human pluripotent
      stem cells in vitro lack the glucose responsiveness characteristic of mature beta
      cells. Beta-cell maturation in mice was studied to find genetic markers that
      enable screens for factors that induce bona fide beta cells in vitro. We find
      that functional beta-cell maturation is marked by an increase in the glucose
      threshold for insulin secretion and by expression of the gene urocortin 3.

PMID- 22371084
TI  - Systematic dissection and optimization of inducible enhancers in human cells
      using a massively parallel reporter assay.
AB  - Learning to read and write the transcriptional regulatory code is of central
      importance to progress in genetic analysis and engineering. Here we describe a
      massively parallel reporter assay (MPRA) that facilitates the systematic
      dissection of transcriptional regulatory elements. In MPRA, microarray
      synthesized DNA regulatory elements and unique sequence tags are cloned into
      plasmids to generate a library of reporter constructs. These constructs are
      transfected into cells and tag expression is assayed by high-throughput
      sequencing. We apply MPRA to compare >27,000 variants of two inducible enhancers
      in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible
      interferon-beta enhancer. We first show that the resulting data define accurate
      maps of functional transcription factor binding sites in both enhancers at single
      nucleotide resolution. We then use the data to train quantitative sequence
      activity models (QSAMs) of the two enhancers. We show that QSAMs from two
      cellular states can be combined to design enhancer variants that optimize
      potentially conflicting objectives, such as maximizing induced activity while
      minimizing basal activity.

PMID- 22371085
TI  - ADHD and delinquency--a developmental perspective.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      psychiatric disorders of childhood and adolescence. Until now, it has been
      unclear whether ADHD by itself constitutes a risk factor for later delinquency or
      does so only in combination with other disruptive symptoms. This article seeks to
      give a comprehensive account of the literature to shed light on the developmental
      pathway from childhood ADHD to adult criminality. Comorbid ADHD and conduct
      disorder (CD) are significantly related to a range of biological and
      environmental risk factors such as neurocognitive impairment, high parental
      psychopathology, poor social functioning, and other comorbid mental disorders,
      particularly substance abuse, that are described in this review. In addition, the
      results of treatment studies are presented, with a special focus on the results
      of the Multimodal Treatment Study of Children with ADHD (MTA). Although treatment
      programs, including medication and psychosocial treatment, can be very effective
      in improving the functioning of children with ADHD in the social and academic
      domains in the short term, there is no conclusive evidence that such treatments
      lower the risk for developing delinquency in adulthood.

PMID- 22371086
TI  - Age-related neural differences in affiliation and isolation.
AB  - While previous aging studies have focused on particular components of social
      perception (e.g., theory of mind, self-referencing), little is known about age
      related differences specifically for the neural basis of perception of
      affiliation and isolation. This study investigates age-related similarities and
      differences in the neural basis of affiliation and isolation. Participants viewed
      images of affiliation (groups engaged in social interaction) and isolation (lone
      individuals), as well as nonsocial stimuli (e.g., landscapes), while making
      pleasantness judgments and undergoing functional neuroimaging (BOLD fMRI).
      Results indicated age-related similarities in response to affiliation and
      isolation in recruitment of regions involved in theory of mind and self
      referencing (e.g., temporal pole, medial prefrontal cortex). Yet age-related
      differences also emerged in response to affiliation and isolation in regions
      implicated in the theory of mind, as well as self-referencing. Specifically, in
      response to isolation versus affiliation images, older adults showed greater
      recruitment than did younger adults of the temporal pole, a region that is
      important for retrieval of personally relevant memories utilized to understand
      others' mental states. Furthermore, in response to images of affiliation versus
      isolation, older adults showed greater recruitment than did younger adults of the
      precuneus, a region implicated in self-referencing. We suggest that age-related
      divergence in neural activation patterns underlying judgments of scenes depicting
      isolation versus affiliation may indicate that older adults' theory of mind
      processes are driven by retrieval of isolation-relevant information. Moreover,
      older adults' greater recruitment of the precuneus for affiliation versus
      isolation suggests that the positivity bias for emotional information may extend
      to social information involving affiliation.

PMID- 22371087
TI  - Optimizing the role of FDG PET-CT for potentially operable metastatic colorectal
      cancer.
AB  - Recent treatment advances now allow a realistic chance of cure in selected
      patients with metastatic colorectal carcinoma (CRC). Accurate pre-treatment
      staging is crucial to ensure appropriate management by identification of patients
      with more advanced disease who will not benefit from surgery. (18)Fluorine 2
      fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (PET
      CT) has a firmly established role in staging, restaging, and recurrence detection
      of a range of tumors. This article will review the role of PET-CT in patients
      with CRC with a particular emphasis on optimizing the technique in patients with
      potentially operable metastatic disease.

PMID- 22371088
TI  - Coupling calcium/calmodulin-mediated signaling and herbivore-induced plant
      response through calmodulin-binding transcription factor AtSR1/CAMTA3.
AB  - Calcium/calmodulin (Ca(2+)/CaM) has long been considered a crucial component in
      wound signaling pathway. However, very few Ca(2+)/CaM-binding proteins have been
      identified which regulate plant responses to herbivore attack/wounding stress. We
      have reported earlier that a family of Ca(2+)/CaM-binding transcription factors
      designated as AtSRs (also known as AtCAMTAs) can respond differentially to
      wounding stress. Further studies revealed that AtSR1/CAMTA3 is a negative
      regulator of plant defense, and Ca(2+)/CaM-binding to AtSR1 is indispensable for
      the suppression of salicylic acid (SA) accumulation and disease resistance. Here
      we report that Ca(2+)/CaM-binding is also critical for AtSR1-mediated herbivore
      induced wound response. Interestingly, atsr1 mutant plants are more susceptible
      to herbivore attack than wild-type plants. Complementation of atsr1 mutant plants
      by overexpressing wild-type AtSR1 protein can effectively restore plant
      resistance to herbivore attack. However, when mutants of AtSR1 with impaired CaM
      binding ability were overexpressed in atsr1 mutant plants, plant resistance to
      herbivore attack was not restored, suggesting a key role for Ca(2+)/CaM-binding
      in wound signaling. Furthermore, it was observed that elevated SA levels in atsr1
      mutant plants have a negative impact on both basal and induced biosynthesis of
      jasmonates (JA). These results revealed that Ca(2+)/CaM-mediated signaling
      regulates plant response to herbivore attack/wounding by modulating the SA-JA
      crosstalk through AtSR1.

PMID- 22371089
TI  - The role of microRNAs in arterial remodelling.
AB  - Adaptive alterations of the vessel wall architecture, called vascular
      remodelling, can be found in arterial hypertension, during the formation of
      aneurysms, in restenosis after vascular interventions, and in atherosclerosis.
      MicroRNAs (miR) critically affect the main cellular players in arterial
      remodelling and may either promote or inhibit the structural changes in the
      vessel wall. They regulate the phenotype of smooth muscle cells (SMCs) and
      control the inflammatory response in endothelial cells and macrophages. In SMCs,
      different sets of miRs induce either a synthetic or contractile phenotype,
      respectively. The conversion into a synthetic SMC phenotype is a crucial event in
      arterial remodelling. Therefore, reprogramming of the SMC phenotype by miR
      targeting can modulate the remodelling process. Furthermore, the effects of
      stimuli that induce remodelling, such as shear stress, angiotensin II, oxidised
      low-density lipoprotein, or apoptosis, on endothelial cells are mediated by miRs.
      The endothelial cell-specific miR-126, for example, is transferred in
      microvesicles from apoptotic endothelial cells and plays a protective role in
      atherogenesis. The inflammatory response of the innate immune system, especially
      through macrophages, promotes arterial remodelling. miR-155 induces the
      expression of inflammatory cytokines, whereas miR-146a and miR-147 are involved
      in the resolution phase of inflammation. However,  in vivo  data on the role of
      miRs in vascular remodelling are still scarce, which are required to test the
      therapeutic potential of the available, highly effective miR inhibitors.

PMID- 22371091
TI  - Single-cell analysis of Bacillus subtilis biofilms using fluorescence microscopy
      and flow cytometry.
AB  - Biofilm formation is a general attribute to almost all bacteria( 1-6). When
      bacteria form biofilms, cells are encased in extracellular matrix that is mostly
      constituted by proteins and exopolysaccharides, among other factors (7-10). The
      microbial community encased within the biofilm often shows the differentiation of
      distinct subpopulation of specialized cells (11-17). These subpopulations coexist
      and often show spatial and temporal organization within the biofilm ( 18-21).   
      Biofilm formation in the model organism Bacillus subtilis requires the
      differentiation of distinct subpopulations of specialized cells. Among them, the
      subpopulation of matrix producers, responsible to produce and secrete the
      extracellular matrix of the biofilm is essential for biofilm formation (11,19).
      Hence, differentiation of matrix producers is a hallmark of biofilm formation in
      B. subtilis.    We have used fluorescent reporters to visualize and quantify the
      subpopulation of matrix producers in biofilms of B. subtilis (15,19,22-24).
      Concretely, we have observed that the subpopulation of matrix producers
      differentiates in response to the presence of self-produced extracellular signal
      surfactin (25). Interestingly, surfactin is produced by a subpopulation of
      specialized cells different from the subpopulation of matrix producers (15).   
      We have detailed in this report the technical approach necessary to visualize and
      quantify the subpopulation of matrix producers and surfactin producers within the
      biofilms of B. subtilis. To do this, fluorescent reporters of genes required for
      matrix production and surfactin production are inserted into the chromosome of B.
      subtilis. Reporters are expressed only in a subpopulation of specialized cells.
      Then, the subpopulations can be monitored using fluorescence microscopy and flow
      cytometry (See Fig 1).    The fact that different subpopulations of specialized
      cells coexist within multicellular communities of bacteria gives us a different
      perspective about the regulation of gene expression in prokaryotes. This protocol
      addresses this phenomenon experimentally and it can be easily adapted to any
      other working model, to elucidate the molecular mechanisms underlying phenotypic
      heterogeneity within a microbial community.

PMID- 22371090
TI  - Exposure study to examine chemosensory effects of formaldehyde on hyposensitive
      and hypersensitive males.
AB  - OBJECTIVE: Main objective of this study was to examine the chemosensory effects
      of formaldehyde on hyposensitive and hypersensitive males at concentrations
      relevant to the workplace. Attention focused on objective effects on and
      subjective symptoms of the mucous membranes of the eyes, the nose, the upper
      respiratory tract and olfactory function. METHODS: Forty-one male volunteers were
      exposed for 5 days (4 h per day) in a randomised schedule to the control
      condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to
      0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8
      ppm, respectively. Peak exposures were carried out four times a day over a 15-min
      period of time. Subjective pain perception induced by nasal application of carbon
      dioxide served as indicator for sensitivity to sensory nasal irritation. The
      following parameters were examined before and after exposure: subjective rating
      of symptoms and complaints (Swedish Performance Evaluation System), conjunctival
      redness, eye-blinking frequency, self-reported tear film break-up time and nasal
      flow rates. In addition, the influence of personality factors on the volunteer's
      subjective scoring was examined (Positive And Negative Affect Schedule). RESULTS:
      Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of
      0.8 ppm for 15 min caused no significant sensory irritation of the measured
      conjunctival and nasal parameters. No differences between hypo- and
      hypersensitive subjects were seen. Nevertheless, statistically significant
      differences were noted for olfactory symptoms, especially for the 'perception of
      impure air'. These subjective complaints were more pronounced in hypersensitive
      subjects. CONCLUSIONS: Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4
      ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects
      related to irritation, and no differences between hypo- and hypersensitive
      subjects were observed.

PMID- 22371092
TI  - The effect of drag suit training on 50-m freestyle performance.
AB  - Little research has evaluated the effects of drag suit training in swimming;
      these effects need to be explored further to optimize their use in training. For
      this 5-week training study, 18 subjects were divided evenly into 2 groups:
      control group and drag suit-trained group. Both groups performed weekly training
      routines that included 3 sprint sets. These sprint sets were performed by both
      the groups; however, the drag suit training group wore the drag suit, and the
      control group wore their typical training attire. We evaluated the swimmers' 50-m
      performance using a test set of six 50-m sprints on a 10-minute interval before
      and after the training program. The test set was performed twice (on 2 different
      days) where the swimmers were tested once in the drag suit and once in their
      regular training attire; the order of testing was randomized. Final time, stroke
      rate, and distance per stroke were collected. We observed that the drag suit
      trained group exhibited a statistically significant decrease in distance per
      stoke while wearing the drag suit and the control group showed a significant
      increase in stroke rate and decrease in distance per stroke (in both suits). It
      is suggested to include some amounts of drag suit training in periods where
      swimming volume may decrease. Sets that are short in distance and performed at
      high intensity with sufficient rest to allow swimmers to maintain high stroke
      integrity should help athletes maintain techniques. We suggest incorporating the
      drag suit into the training regimen and should be considered a valuable resistive
      training device for swimming.

PMID- 22371093
TI  - Effects of bone-conducted music on swimming performance.
AB  - Music has been shown to be a useful adjunct for many forms of exercise and has
      been observed to improve athletic performance in some settings. Nonetheless,
      because of the limited availability of practical applications of sound conduction
      in water, there are few studies of the effects of music on swimming athletes. The
      SwiMP3 is a novel device that uses bone conduction as a method to circumvent the
      obstacles to transmitting high fidelity sound in an aquatic environment. Thus, we
      studied the influence of music on swimming performance and enjoyment using the
      SwiMP3. Twenty-four competitive swimmers participated in a randomized crossover
      design study in which they completed timed swimming trials with and without the
      use of music delivered via bone conduction with the SwiMP3. Each participant swam
      four 50-m trials and one 800-m trial and then completed a physical enjoyment
      survey. Statistically significant improvements in swimming performance times were
      found in both the 50-m (0.32 seconds; p = 0.013) and 800-m (6.5 seconds; p =
      0.031) trials with music using the SwiMP3. There was no significant improvement
      in physical enjoyment with the device as measured by a validated assessment tool.
      Bone-conducted music appears to have a salutary influence on swimming performance
      in a practice environment among competitive adult swimmers.

PMID- 22371094
TI  - Relationship of body mass index and fitness levels among schoolchildren.
AB  - Childhood obesity is an epidemic in the U.S.A., and understanding aspects of
      fitness is critical in implementing effective interventions. The purpose of this
      study was to analyze the relationship of obesity levels with the fitness levels
      of public school children in Louisiana. Over 7,000 school children participated
      in body mass index (BMI) and Fitnessgram(r) subtests including the Progressive
      Aerobic Cardiovascular Endurance Run (aerobic capacity), curl-ups, trunk lifts,
      push-ups (strength and endurance), and shoulder stretches (flexibility). The
      fitness measures and BMI were analyzed using chi-square and logistic regression
      to test for any significant relationships. The results indicated that the
      participants with healthy BMIs have the highest levels of physical fitness. The
      differences between the fitness levels of obese and healthy children were
      statistically significant. This study demonstrated a direct relationship between
      BMI status and fitness levels as measured by the Fitnessgram(r) among study
      participants. This finding is not exceedingly surprising, as common sense tells
      us that the heavier a person is, the less likely he or she is to be physically
      fit. However, this study is an important first step in understanding weight
      issues in children. This information can be used to develop data-driven
      interventions to assist children in becoming healthier and more physically fit.

PMID- 22371096
TI  - The effects of a sudden salinity change on cortisol, glucose, lactate, and
      osmolality levels in grouper Epinephelus malabaricus.
AB  - Grouper Epinephelus malabaricus (weighing 46.37 +/- 5.10 g) previously maintained
      in 240/00 seawater were transferred to 14, 19, 24 (control), 29, and 340/00
      seawater. Serum cortisol, glucose, lactate, and osmolality levels were measured
      at 7 time points during 240 min. Serum cortisol and glucose levels of fish
      transferred to 29 and 340/00 seawater significantly increased to the highest
      after 10 and 20 min, respectively. No significant differences in serum cortisol
      and glucose levels were observed for the fish after 30 min among all treatments.
      Serum lactate level of fish transferred to 14, 19, 29, and 340/00 seawater was
      significantly lower than that of the control fish after 10-30 min. However, no
      significant differences in serum lactate were observed 60 min among five
      treatments. The serum osmolality of the fish following 240-min transfer increased
      directly with salinity, whereas the osmoregulatory capacity value (medium
      osmolality-plasma osmolality) of the fish following 240-min transfer was
      inversely related to salinity. It is concluded that grouper showed strong
      osmoregulation in 14-340/00 seawater. Serum cortisol and glucose levels of fish
      transferred to 29 and 340/00 seawater increased rapidly in 10-30 min, indicating
      an early stress response.

PMID- 22371095
TI  - Mitochondrial HSP70 cognate-mediated differential expression of JNK1/2 in the
      pollution stressed grey mullets, Mugil cephalus.
AB  - Cells have evolved different networks of cellular stress responses to adapt
      during environmental changes and survive combating wide variety of stress.
      Mitochondrial heat shock protein 70 (mtHSP70) are essential for maintaining
      cellular homeostasis. c-Jun-N terminal kinase (JNK), a subfamily of MAPK, plays a
      key role in the transmission of extracellular signal for survival and death. In
      the present investigation, the differential expression of phosphorylated JNK1/2
      with corresponding increases in heat shock transcription factor-1 (HSF-1) under
      high levels of B-cell lymphoma 2 (Bcl-2), HSP70 transcripts (twofold) and mtHSP70
      has been correlated with fish survival in polluted Ennore estuary. This study
      suggests that in Ennore sample, the amplification in HSP70 transcripts along with
      corresponding mtHSP70 overexpression might be due to activation of JNK1/2 and HSF
      1. This would influence the expression of Bcl-2 protein involved in mitochondrial
      survival under pollution-stressed condition.

PMID- 22371097
TI  - Synthesis and structure-activity relationships of o-sulfonamido-arylhydrazides as
      inhibitors of LL-diaminopimelate aminotransferase (LL-DAP-AT).
AB  - Recently, LL-diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal-5'
      phosphate (PLP)-dependent enzyme, was reported to catalyze a key step in the
      biosynthesis of L-lysine in plants and Chlamydia. Previous screening of a 29,201
      compound library against LL-DAP-AT identified an o-sulfonamidoarylhydrazide as a
      reversible inhibitor with IC(50)~ 5 MUM. Structure-activity relationship (SAR)
      studies based on this lead compound identified key structural features essential
      for enzyme inhibition and led to slightly improved inhibitors. Preliminary
      studies on the mode of inhibition of LL-DAP-AT by this class of compounds are
      also reported.

PMID- 22371098
TI  - Relationship between premenstrual symptoms and dysmenorrhea in Japanese high
      school students.
AB  - To determine the relationship between premenstrual symptoms and dysmenorrhea
      among Japanese adolescent girls, a total of 1,431 high school students were
      assessed. Of them, 11.3% were classified with "moderate to severe premenstrual
      syndrome (PMS)" and 3.2% with "premenstrual dysphoric disorder (PMDD)." Eighty
      five percent of the girls had dysmenorrhea. The rates of prevalence of PMDD and
      moderate to severe PMS were increased according to the severity of dysmenorrhea
      (rs = 0.479), showing a correlation between the severity of PMS/PMDD and
      dysmenorrhea in adolescents.

PMID- 22371099
TI  - Technical note: tree truthing: how accurate are substrate estimates in primate
      field studies?
AB  - Field studies of primate positional behavior typically rely on ground-level
      estimates of substrate size, angle, and canopy location. These estimates
      potentially influence the identification of positional modes by the observer
      recording behaviors. In this study we aim to test ground-level estimates against
      direct measurements of support angles, diameters, and canopy heights in trees at
      La Suerte Biological Research Station in Costa Rica. After reviewing methods that
      have been used by past researchers, we provide data collected within trees that
      are compared to estimates obtained from the ground. We climbed five trees and
      measured 20 supports. Four observers collected measurements of each support from
      different locations on the ground. Diameter estimates varied from the direct tree
      measures by 0-28 cm (Mean: 5.44 +/- 4.55). Substrate angles varied by 1-55
      degrees  (Mean: 14.76 +/- 14.02). Height in the tree was best estimated using a
      clinometer as estimates with a two-meter reference placed by the tree varied by 3
      11 meters (Mean: 5.31 +/- 2.44). We determined that the best support size
      estimates were those generated relative to the size of the focal animal and
      divided into broader categories. Support angles were best estimated in 5 degrees 
      increments and then checked using a Haglof clinometer in combination with a laser
      pointer. We conclude that three major factors should be addressed when estimating
      support features: observer error (e.g., experience and distance from the target),
      support deformity, and how support size and angle influence the positional mode
      selected by a primate individual. individual.

PMID- 22371100
TI  - Supramolecular concepts and new techniques in mechanochemistry: cocrystals,
      cages, rotaxanes, open metal-organic frameworks.
AB  - Mechanochemical reactions effected by milling or grinding are an attractive means
      to conduct chemical reactions dependent on molecular recognition and to
      systematically explore different modes of molecular self-assembly. The natural
      relationship between milling mechanochemistry and supramolecular chemistry arises
      primarily from the ability to avoid bulk solvent, which simultaneously avoids
      limitations of solution-based chemistry, such as solubility, solvent
      complexation, or solvolysis, and makes the resulting process highly
      environmentally friendly. This tutorial review highlights the use of
      mechanochemistry for the synthesis of supramolecular targets in the solid state,
      such as molecular hydrogen- or halogen-bonded complexes, molecular and
      supramolecular cages, open frameworks and interlocked architectures. It is also
      demonstrated that the molecular self-assembly phenomena that are well-established
      in solution chemistry, such as reversible binding through covalent or non
      covalent bonds, thermodynamic equilibration and structure templating, are also
      accessible in milling mechanochemistry through recently developed highly
      efficient methodologies such as liquid-assisted grinding (LAG) or ion- and liquid
      assisted grinding (ILAG). Also highlighted are the new opportunities arising from
      the marriage of concepts of supramolecular and mechanochemical synthesis,
      including organocatalysis, deracemisation and discovery of new molecular
      recognition motifs.

PMID- 22371101
TI  - Sleeping site selection by golden-backed uacaris, Cacajao melanocephalus ouakary
      (Pitheciidae), in Amazonian flooded forests.
AB  - In Amazonian seasonally flooded forest (igapo), golden-backed uacaris, Cacajao
      melanocephalus ouakary, show high selectivity for sleeping trees. Of 89 tree
      species in igapo, only 16 were used for sleeping (18%). Hydrochorea marginata
      (Fabaceae) and Ormosia paraensis (Fabaceae) were used most frequently (41% of
      records) despite being uncommon (Ivlev electivity ratios were 0.76, and 0.84,
      respectively), though the third most commonly used species (11%), Amanoa
      oblongifolia (Euphorbiaceae), was selected at near parity. All three species have
      broad, open canopies with large horizontal limbs and uncluttered interiors.
      Compared with random trees, sleeping trees had above average diameter at breast
      height (DBH) and height, lacked lianas and wasp nests, and were more frequently
      within 5 m of open water. Uacaris generally slept one adult per tree or widely
      separated in the same canopy and on the outer third of the branch. These
      behaviours are interpreted as maximising detection of both aerial and arboreal
      predators.

PMID- 22371102
TI  - Epidemiological, bacteriological and molecular studies on caseous lymphadenitis
      in Sirohi goats of Rajasthan, India.
AB  - Corynebacterium pseudotuberculosis is the causative agent of caseous
      lymphadenitis (CL), a chronic debilitating disease of goats. In the present
      study, a total of 575 goats of Sirohi breed on an organized farm situated in the
      semi-arid tropical region of Rajasthan, India were clinically examined. Pus
      samples from superficial lymph nodes of 27 (4.7%) adult goats presenting clinical
      lesions suggestive of CL were collected for bacteriological and molecular
      analyses. Of these goats, 51.9% yielded C. pseudotuberculosis on the basis of
      morphological, cultural and biochemical characteristics. A polymerase chain
      reaction (PCR) assay targeting proline iminopeptidase gene specific to C.
      pseudotuberculosis was developed that confirmed all 14 bacterial isolates. The
      specificity of the PCR product was confirmed by sequencing of the 551-bp amplicon
      in both senses, showing 98-100% homology with published sequences. Thus, overall
      prevalence rate based on clinical, bacterial culture and PCR assay were found to
      be 4.7%, 2.4% and 2.4%, respectively. The PCR assay developed in this study was
      found to be specific and rapid, and could be used for confirmation of CL in goats
      as an alternative method to generally cumbersome, time-consuming and less
      reliable conventional methods.

PMID- 22371103
TI  - [Epidemiology of mental health care].
AB  - Mental health care epidemiology seeks to investigate the practical situation of
      the health care system and services for individuals with mental disorders. In the
      past decades, mental health care structures in Germany were successively
      transformed from long-term inpatient treatment capacities to decentralized
      outpatient and day clinic services. Currently, the proportional relation between
      treatment facilities in different settings has been stabilized and the strategy
      of mental health care development focuses on innovative and integrative models of
      care provision. The aim is to integrate fragmented services by the introduction
      of network structures to overcome rigid sector boundaries. The need for health
      care services is associated with multiple factors such as population-based
      epidemiological data, usage behavior, and health politics. Due to scarce data and
      poor standards of care it is difficult to determine if current structures of
      mental health services cover the actual needs. Therefore, a substantial increase
      of mental health service research is needed.

PMID- 22371104
TI  - Oral direct factor Xa inhibitors for stroke prevention in atrial fibrillation.
AB  - Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as
      the number of patients with this condition continues to increase. Several novel
      oral anticoagulants are being developed as replacements for warfarin for this
      indication. Direct factor Xa inhibitors comprise the largest class of oral
      anticoagulants in development; the inhibition of factor Xa is recognized to be a
      promising target for therapeutic anticoagulation, partly because of its location
      in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are
      small-molecule, selective inhibitors that directly and reversibly bind to the
      active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles
      vary, which might allow patient-specific therapy. Several of these agents have
      been tested in clinical trials for various indications, including AF, with
      favorable results. In particular, apixaban and rivaroxaban have shown superiority
      and noninferiority, respectively, to warfarin in phase III clinical trials for
      stroke prevention in AF. These agents have also been shown to be safe in terms of
      bleeding risk. Despite these advantages, factor Xa inhibitors have several
      characteristics, such as potential interactions with other drugs (inhibitors of
      cytochrome P450 and P-glycoprotein) and the inability to reverse their
      anticoagulant effects, as well as concerns about poor patient compliance, which
      must be considered when initiating patients on a novel factor Xa inhibitor.

PMID- 22371107
TI  - Coronary artery disease: Y chromosome link to CAD risk.

PMID- 22371105
TI  - World Heart Federation criteria for echocardiographic diagnosis of rheumatic
      heart disease--an evidence-based guideline.
AB  - Over the past 5 years, the advent of echocardiographic screening for rheumatic
      heart disease (RHD) has revealed a higher RHD burden than previously thought. In
      light of this global experience, the development of new international
      echocardiographic guidelines that address the full spectrum of the rheumatic
      disease process is opportune. Systematic differences in the reporting of and
      diagnostic approach to RHD exist, reflecting differences in local experience and
      disease patterns. The World Heart Federation echocardiographic criteria for RHD
      have, therefore, been developed and are formulated on the basis of the best
      available evidence. Three categories are defined on the basis of assessment by
      2D, continuous-wave, and color-Doppler echocardiography: 'definite RHD',
      'borderline RHD', and 'normal'. Four subcategories of 'definite RHD' and three
      subcategories of 'borderline RHD' exist, to reflect the various disease patterns.
      The morphological features of RHD and the criteria for pathological mitral and
      aortic regurgitation are also defined. The criteria are modified for those aged
      over 20 years on the basis of the available evidence. The standardized criteria
      aim to permit rapid and consistent identification of individuals with RHD without
      a clear history of acute rheumatic fever and hence allow enrollment into
      secondary prophylaxis programs. However, important unanswered questions remain
      about the importance of subclinical disease (borderline or definite RHD on
      echocardiography without a clinical pathological murmur), and about the
      practicalities of implementing screening programs. These standardized criteria
      will help enable new studies to be designed to evaluate the role of
      echocardiographic screening in RHD control.

PMID- 22371106
TI  - Prevention. Aspirin in primary prevention--good news and bad news.
AB  - The balance of benefits and risks of aspirin in primary prevention is far less
      clear than in secondary prevention; further data from randomized trials of
      individuals at intermediate cardiovascular risk are needed. Decisions about
      aspirin in primary prevention should be made on a case-by-case basis, and general
      guidelines are not justified.

PMID- 22371108
TI  - Acute coronary syndromes. Challenging accepted post-MI serum potassium targets.
AB  - On the basis of high-quality observational data, Goyal et al. have found that
      serum potassium levels <3.5 mmol/l or >=4.5 mmol/l are associated with increased
      in-hospital mortality in patients with acute myocardial infarction. We discuss
      whether target potassium levels in clinical practice and guidelines should be
      changed to 3.5-4.5 mmol/l.

PMID- 22371109
TI  - Interventional cardiology: Don't neglect the octogenarians--DES for everyone!?

PMID- 22371110
TI  - Acute coronary syndromes: Is early abciximab beneficial in STEMI?

PMID- 22371111
TI  - Stem cells: Myocardial regeneration after infarction-promising phase I trial
      results.

PMID- 22371112
TI  - Hip arthroscopy: evolution, current practice and future developments.
AB  - Arthroscopic examination and treatment is an ever-increasing part of modern
      orthopaedic practice in this age of minimally invasive surgery. Arthroscopic
      procedures have been widespread in surgery of the knee and the shoulder for many
      years; however, the hip until relatively recently, has been largely neglected.
      Even now hip arthroscopy is not widely available; this may be due to the
      complexity of the procedure, the requirement of specialist equipment and a
      reportedly long learning curve. On the other hand, it has gone through a period
      of rapid growth over the last decade and is being performed in large numbers
      routinely in some centres around the world. Hip arthroscopy now provides
      excellent visualisation of not only the articular surfaces of the hip joint but
      also of the peritrochanteric or extra-articular space around the hip. Pathology
      of both the femoral head and the acetabulum along with the soft tissues of the
      hip, namely the ligamentum teres, the acetabular labrum, the synovial folds and
      synovium, is readily diagnosed. Modern techniques provide therapeutic options for
      a myriad of conditions and allow modulation of pathological processes early.
      Additionally hip arthroscopy is a relatively safe procedure with few
      complications and contraindications. However, the key to good outcomes is in the
      careful selection of patients and meticulous surgical technique. The aim of this
      review is to bring the reader up to date with an overview of the evolution of
      arthroscopy of the hip, review the current practice and explore possible future
      developments.

PMID- 22371113
TI  - The EOSTM imaging system and its uses in daily orthopaedic practice.
AB  - BACKGROUND: The EOSTM X-ray machine, based on a Nobel prize-winning invention in
      physics in the field of particle detection, is capable of a simultaneous capture
      of biplanar X-ray images by slot scanning of the whole body in an upright,
      physiological load-bearing position, using ultra-low radiation doses. The
      simultaneous capture of spatially calibrated anterioposterior and lateral images
      provides a three-dimensional (3D) surface reconstruction of the skeletal system
      using a special software. Parts of the skeletal system in X-ray images and 3D
      reconstructed models appear in true 1:1 scale for size and volume, thus spinal
      and vertebral parameters, lower limb axis lengths and angles, as well as any
      relevant clinical parameters in orthopaedic practice can be very precisely
      measured and calculated. Visualisation of 3D reconstructed models in various
      views by sterEOS 3D software enables presentation of top view images to help
      analyse rotational conditions of lower limbs, joints and spine deformities in the
      horizontal plane, providing revolutionary novel possibilities in orthopaedic
      surgery, especially in spine surgery. APPROACH AND CONCLUSIONS: Our department
      has been extensively using the very first commercially available EOSTM imaging
      system worldwide for routine orthopaedic diagnostics since June 2007. During this
      period of about 4.5 years, more than 5,700 standard examinations have been
      carried out, about a third of them in spine deformity cases and the rest in lower
      limb orthopaedic cases. In this mini-review, general principles and uses of this
      groundbreaking integrated orthopaedic solution is reviewed with a few highlighted
      examples from our own clinical practice.

PMID- 22371114
TI  - Whole-body vibration and resistance exercise prevent long-term hindlimb unloading
      induced bone loss: independent and interactive effects.
AB  - Skeletal unloading induced by disuse or immobilization causes a decrease in bone
      mass and strength. We investigated the relationship between whole-body vibration
      (WBV) and resistance exercise (RE) in preventing bone loss induced by 8-week
      hindlimb unloading in young male rats. Sixty male Wistar rats were assigned
      randomly to 6 groups: age-matched control group (CON, n = 10), hindlimb unloading
      group (HU, n = 10), hindlimb unloading + standing group (HU + ST, n = 10),
      hindlimb unloading + WBV group (HU + WBV, n = 10), hindlimb unloading + RE group
      (HU + RE, n = 10) and hindlimb unloading + WBV + RE group (HU + WBV + RE, n =
      10). After 8-week hindlimb unloading, micro-CT scanning and three-point bending
      test were performed in the femur. Sera were collected for analysis of bone
      formation and resorption markers. Compared with HU group, WBV, RE and the
      combination of WBV and RE (WBV + RE) significantly improved (P < 0.01) one
      repetition maximum (1RM) (expressed as the percentage change from baseline, HU: 
      23%, HU + WBV: 21%, HU + RE: 48%, HU + WBV + RE: 51%), and maintained (P < 0.05)
      cancellous volumetric bone mineral density (vBMD) and trabecular structure. No
      difference of cortical vBMD was found among all groups (P > 0.05). WBV had no
      effects on biomechanical properties of the femur diaphysis (P > 0.05). RE and WBV
      + RE significantly increased maximum load and cross-sectional moment of inertia
      of the femur diaphysis in hindlimb unloading rats (P < 0.05). There was an
      interaction between WBV and RE in improving cancellous bone. These results
      demonstrate that WBV and RE interactively maintain cancellous structure and vBMD,
      and independently partially mitigate the reduction of bone strength in long-term
      hindlimb unloading rats.

PMID- 22371115
TI  - Non-severe allergic asthma is associated with elevated plasma protein C and
      protein S.

PMID- 22371116
TI  - Growth of Mycobacterium tuberculosis biofilms.
AB  - Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, has an
      extraordinary ability to survive against environmental stresses including
      antibiotics. Although stress tolerance of M. tuberculosis is one of the likely
      contributors to the 6-month long chemotherapy of tuberculosis (1), the molecular
      mechanisms underlying this characteristic phenotype of the pathogen remain
      unclear. Many microbial species have evolved to survive in stressful environments
      by self-assembling in highly organized, surface attached, and matrix encapsulated
      structures called biofilms (2-4). Growth in communities appears to be a preferred
      survival strategy of microbes, and is achieved through genetic components that
      regulate surface attachment, intercellular communications, and synthesis of
      extracellular polymeric substances (EPS) (5,6). The tolerance to environmental
      stress is likely facilitated by EPS, and perhaps by the physiological adaptation
      of individual bacilli to heterogeneous microenvironments within the complex
      architecture of biofilms (7).    In a series of recent papers we established that
      M. tuberculosis and Mycobacterium smegmatis have a strong propensity to grow in
      organized multicellular structures, called biofilms, which can tolerate more than
      50 times the minimal inhibitory concentrations of the anti-tuberculosis drugs
      isoniazid and rifampicin (8-10). M. tuberculosis, however, intriguingly requires
      specific conditions to form mature biofilms, in particular 9:1 ratio of
      headspace: media as well as limited exchange of air with the atmosphere (9).
      Requirements of specialized environmental conditions could possibly be linked to
      the fact that M. tuberculosis is an obligate human pathogen and thus has adapted
      to tissue environments. In this publication we demonstrate methods for culturing
      M. tuberculosis biofilms in a bottle and a 12-well plate format, which is
      convenient for bacteriological as well as genetic studies. We have described the
      protocol for an attenuated strain of M. tuberculosis, mc(2)7000, with deletion in
      the two loci, panCD and RD1, that are critical for in vivo growth of the pathogen
      (9). This strain can be safely used in a BSL-2 containment for understanding the
      basic biology of the tuberculosis pathogen thus avoiding the requirement of an
      expensive BSL-3 facility. The method can be extended, with appropriate
      modification in media, to grow biofilm of other culturable mycobacterial species.
      Overall, a uniform protocol of culturing mycobacterial biofilms will help the
      investigators interested in studying the basic resilient characteristics of
      mycobacteria. In addition, a clear and concise method of growing mycobacterial
      biofilms will also help the clinical and pharmaceutical investigators to test the
      efficacy of a potential drug.

PMID- 22371117
TI  - Stereoselective synthesis of novel pyrazole derivatives using tert
      butansulfonamide as a chiral auxiliary.
AB  - A novel chiral pyrazole derivative was developed by our research program as a
      potent PDE4 inhibitor for the treatment of anti-inflammatory diseases, such as
      asthma and chronic obstructive pulmonary disease. The asymmetric synthesis of the
      inhibitors carrying the pyrazole moiety, including nitrogen directly bonded to a
      chiral center, through a novel approach is disclosed. The key steps of the
      synthetic sequence begin with the preparation of chiral toluenesulfinyl imine by
      the condensation of (R)- and (S)-tert-butanesulfinamide with an aldehyde. Next, a
      corresponding chiral amine synthesis by a stereoselective addition reaction of 4
      picolyl lithium to the chiral toluenesulfinyl imine is performed, followed by
      desulfination. The preparation of the cis-type enaminone from the addition of the
      enaminone to the corresponding chiral amine is then accomplished, with further
      transformation into the pyrazole derivatives through the amination of the
      enaminones and subsequent dehydro-cyclization. A total of 8 steps are completed
      to produce a 5.5% yield (100% ee).

PMID- 22371118
TI  - Alphab-crystallin expression in epiretinal membrane of human proliferative
      diabetic retinopathy.
AB  - PURPOSE: To examine the expression of alphaB-crystallin and its colocalization
      with vascular endothelial growth factor in the epiretinal membrane of human
      proliferative diabetic retinopathy. METHODS: Ten epiretinal membranes of
      proliferative diabetic retinopathy and three normal retinas surgically excised
      were included in this study. Paraformaldehyde-fixed, paraffin-embedded tissue
      sections were processed for immunohistochemistry with alphaB-crystallin, vascular
      endothelial growth factor, and CD31 antibodies. RESULTS: AlphaB-crystallin was
      expressed in all epiretinal membranes examined. The immunolocalization of alphaB
      crystallin was detected in the cytoplasm of CD31-positive endothelial cells, but
      not in normal retinal blood vessels. Furthermore, alphaB-crystallin
      immunoreactivity was colocalized in vascular endothelial growth factor-positive
      endothelial cells in proliferative diabetic retinopathy membranes. CONCLUSION:
      AlphaB-crystallin was expressed in proliferative diabetic retinopathy membranes,
      and colocalized with vascular endothelial growth factor-positive neovessels.
      AlphaB-crystallin may play a potential role in the pathogenesis of epiretinal
      membranes in proliferative diabetic retinopathy, together with vascular
      endothelial growth factor.

PMID- 22371119
TI  - Alterations of gene expression of sodium channels in dorsal root ganglion neurons
      of estrogen receptor knockout (ERKO) mice induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP).
AB  - Estrogen receptors (ERalpha and ERbeta) mediate the neuroprotection of estrogens
      against MPTP-induced striatal dopamine (DA) depletion. Pain is an important and
      distressing symptom in Parkinson's disease (PD). Voltage-gated sodium channels in
      sensory neurons are involved in the development of neuropathic pain. In this
      study, MPTP caused changes in nociception and alterations of gene expression of
      voltage-gated sodium channels in dorsal root ganglion (DRG) neurons in ER
      knockout (ERKO) mice were investigated. We found that administration of MPTP (11
      mg/kg) to WT mice led to an extensive depletion of DA and its two metabolites,
      alphaERKO mice were observed to be more susceptible to MPTP toxicity than
      betaERKO or WT mice. In addition, we found that the mRNA levels of TTX-S and TTX
      R sodium channel subtypes were differentially affected in MPTP-treated WT
      animals. The MPTP-induced up-regulation of Nav1.1 and Nav1.9, down-regulation of
      Nav1.6 in DRG neurons may be through ERbeta, up-regulation of Nav1.7 and down
      regulation of Nav1.8 are dependent on both ERalpha and ERbeta. Therefore, the
      MPTP-induced alterations of gene expression of sodium channels in DRG neurons
      could be an important mechanism to affect excitability and nociceptive
      thresholds, and the ERs appear to play a role in nociception in PD.

PMID- 22371120
TI  - More but not less uncertainty makes adult humans' tool selections more similar to
      those reported with crows.
AB  - In this study, we examined whether adult humans' tool selections in a stick-and
      tube problem might resemble previously published results of crows' selections if
      people had more experience solving the problem or were presented with a more
      ambiguous problem. In Experiments 1a and 1b, when given multiple opportunities to
      select a stick from a set of 10 to retrieve a candy located either 8 or 16 cm
      from the opening of a tube, the participants always selected a stick that was
      long enough to retrieve the candy; however, they did not generally select either
      the stick whose length matched the object's distance or the longest stick in the
      set-two outcomes reported in studies with crows. In Experiment 2, participants
      who were allowed only a brief period of time to study the problem selected a
      longer stick than did participants allowed unlimited time to do the same.
      However, only when the candy's distance was 16 cm did these people reliably
      select the longest stick in the set. It seems that increasing, but not
      decreasing, people's uncertainty about a problem can make humans' tool selections
      more similar to those reported with crows.

PMID- 22371121
TI  - Interleukin-1 beta increases activity of human endothelial progenitor cells:
      involvement of PI3K-Akt signaling pathway.
AB  - Interleukin-1beta (IL-1beta) is a multifunctional proinflammatory cytokine
      upregulated in acute phase of heart ischemic disease. Controversial effects of IL
      1beta have been demonstrated on endothelial progenitor cells (EPCs) functional
      activity. The aim of this study was to investigate the in vitro effect of IL
      1beta on activity of human origin EPCs and the possible mechanism involved. EPCs
      were isolated from peripheral blood of healthy volunteers without cardiovascular
      risk factors and characterized. After ex vivo cultivation, EPCs were stimulated
      with a series of final concentrations (0, 0.1, 1, and 10 ng/ml) of IL-1beta for
      24 h. In some other experiments, EPCs were pretreated with 10 MUM LY294002 (Akt
      inhibitor) for 30 min and then stimulated with 1 ng/ml IL-1beta for 24 h. Cell
      proliferation, apoptosis, adhesion, and migration were determined, respectively,
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin
      V/propidium iodide binding assay, adhesion assay, and transwell migration assay.
      In addition, the vascular endothelial vascular growth factor-A (VEGF-A)
      production has been examined using quantitative real-time RT-PCR and ELISA assay.
      Furthermore, the total and phosphorylation level of Akt was determined by Western
      blot. IL-1beta significantly stimulated EPC proliferation, migration, and
      adhesion and upregulated the angiogenic growth factor VEGF-A at mRNA and protein
      level, while exerted no influence on cell apoptosis. However, pretreatment with
      LY294002 significantly diminished IL-1beta-induced proliferation, migration,
      adhesion, and VEGF-A production. One nanogram per milliliter IL-1beta for 15 min
      activated phosphorylation of Akt. These results suggest a potent role for IL
      1beta in upregulating EPCs functions. The phosphatidyl-inositol-3-kinase-Akt
      signaling pathway could be involved in the regulation of EPCs functions induced
      by IL-1beta.

PMID- 22371122
TI  - Oral microbiota in Swiss adolescents.
AB  - OBJECTIVES: The purpose of the study was to determine the prevalence of different
      oral microbes in gingival plaque samples and in samples from the dorsum of the
      tongue in a Swiss adolescent population. MATERIALS AND METHODS: Ninety-nine
      adolescents between 15 and 18 years were enrolled. Plaque index, bleeding on
      probing (BOP), the periodontal screening index, and decayed missed filled tooth
      (DMFT) index were recorded. Samples from subgingival plaque and swabs from the
      tongue were analyzed by the Checkerboard DNA-DNA hybridization method.
      Additionally, counts of Streptococus mutans and Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and
      Treponema denticola were determined by real-time PCR. RESULTS: Periodontitis was
      not diagnosed in any of the subjects but all of them presented signs of gingival
      inflammation displaying a mean BOP of 28%. Ten (10.1%) subjects were tested
      positive for P. gingivalis, each 22 (22.2%) for A. actinomycetemcomitans and T.
      forsythia, (47.5%) for T. denticola. T. denticola and S. mutans showed a high
      affinity to the gingival plaque, whereas T. forsythia was often detected from the
      dorsum of the tongue. DMFT was associated with S. mutans counts, and BOP
      correlated with counts of P. gingivalis and T. denticola. CONCLUSIONS: The
      present data indicate that: (a) gingivitis but not periodontitis is a common
      finding among Swiss adolescents, and (b) bacteria associated with periodontitis
      were frequently detected in the subgingival dental plaque and on the dorsum of
      the tongue in Swiss adolescents with gingivitis. CLINICAL RELEVANCE: Although
      gingivitis was a frequent finding in Swiss adolescents, periodontitis was not
      detected in this population. The dorsum of the tongue appears to represent an
      important reservoir for periodontopathic bacteria.

PMID- 22371124
TI  - TMJ osteoarthritis: a new approach to diagnosis.
AB  - Disorders of the temporomandibular joint (TMJ), including TMJ osteoarthritis (TMJ
      OA), are the topic of intensive clinical research; however, this is not the case
      in the archaeological literature, with the majority of work on the subject
      ceasing with the early 1990s. The methods employed in the diagnosis of TMJ OA
      within the archaeological work appear nonrepresentative of the disease and may
      have led to erroneous assumptions about the pattern and prevalence of OA. This
      current work presents a new method for evaluating OA specifically for the TMJ,
      considering both the biomechanics of the joint and the mechanisms of the disease.
      Totally, 496 specimens (including a group of modern documented specimens) were
      analyzed for the presence of TMJ OA using the following criteria: eburnation,
      osteophytes (marginal and new bone on joint surface), porosity, and alteration to
      joint contour. The results suggest that eburnation occurs rarely in the TMJ, so
      should not be used as an exclusive criterion. Rather a combination of at least
      two of the other criteria should be used, with osteophytes and porosity occurring
      the most frequently on both the mandibular condyle and articular eminence.
      Additionally, the prevalence of TMJ OA in the modern assemblage was similar to
      that observed in current clinical research, suggesting that the method employed
      here was able to produce a reasonable approximation of what is found in
      contemporary living populations.

PMID- 22371125
TI  - Cancer stem cells and their potential implications for the treatment of solid
      tumors.
AB  - BACKGROUND AND OBJECTIVES: There is increasing evidence that a variety of human
      cancers is maintained by a subset of cells, cancer stem cells (CSCs), which
      sustain tumor growth, underlie its malignant behavior, and possibly initiate
      distant metastases. The aim of this review is to evaluate the current evidence
      for the existence of CSCs and the implications on the present management and
      treatment of solid tumors. METHODS: A retrospective review of the English
      language literature (1997-2010) concerning CSCs and their therapeutic
      implications was performed. RESULTS: CSCs are characterized by two main
      properties of normal stem cells: Self-renewal and differentiation, which are best
      assayed by serial transplantation experiments in immunodeficient mice. Cell
      surface antigens that mark cell populations enriched for CSCs have been
      identified in various solid tumors. As such, the very existence of CSCs has vast
      clinical implications with regard to cancer treatment. The development of tailor
      made CSC-targeted therapies (including therapies directed at these CSC-specific
      surface markers, and reversal of the intrinsic resistance of CSCs to chemo- and
      radiotherapy) entails great promises. However, normal stem cell toxicity and
      treatment resistance have been recognized as serious problems. CONCLUSION: The
      growing evidence indicating that CSCs drive and maintain various types of solid
      human malignancies has important implications for the treatment of patients.
      However, over the years the development of CSC-targeted therapies has faced a
      number of potential hurdles, which must be considered carefully in order to
      maximize the chance that such therapies will be successful.

PMID- 22371126
TI  - In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma,
      NMP-22 works for high grades, but unreliable in low grades and upper urinary
      tract tumors.
AB  - INTRODUCTION AND OBJECTIVES: Two percent of the bladder non-muscle-invasive (NMI)
      transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT)
      TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek)
      test in the diagnosis of lower urinary tract and UUT-TCC. METHODS: From March
      2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control
      cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27
      88) patients who were followed regularly with NMP-22 test and with follow-up
      cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For
      routine monitoring of the UUT, IVU or CT urography was used once a year for high
      grades (HG), and once in every other year for low grades (LG). The sensitivity
      and specificity of NMP-22 were evaluated by ROC curves, and sensitivity,
      specificity, and positive and negative predictive values were calculated. Chi
      square test was used for the differences between the subgroups. RESULTS:
      Cystoscopy and NMP-22 results of the patients included in the study revealed the
      sensitivity (44.4%) of the test was very low and the specificity (98.4%) was
      quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but
      cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never
      positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors
      were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be
      negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected
      in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients)
      where both NMP-22 and cystoscopy were negative for tumor. CONCLUSIONS: Nuclear
      matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority
      of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22
      is also not reliable in UUT-TCC, even in HG tumors.

PMID- 22371127
TI  - Bacterial sepsis following prostatic biopsy.
AB  - PURPOSE: Despite the recent innovations, complications of prostate biopsy can
      occur. The aim of this study was a prospective monitoring of major septic
      complications occurring after transrectal prostate biopsy, to describe their
      causing agents, to report the clinical course of these patients, and to give
      guidelines based on our personal experience. METHODS: This prospective study was
      carried out between January 2009 and September 2010. Complications were evaluated
      by telephone interviews. RESULTS: Between January 2009 and September 2010, 447
      (96.5%) completed the telephone interview. Urosepsis occurred in ten patients
      (2.2%) and in three cases evolved into septic shock. Of these ten patients, nine
      had a positive blood culture, of whom eight for Escherichia coli and one for
      Aeromonas hydrophila, Aeromonas caviae, and Aeromonas sobria. In seven cases, the
      E. coli isolated were resistant to fluoroquinolone and six produced an extended
      spectrum beta-lactamase. Six E. coli were classified as multidrug-resistant
      organisms. Of the 10 patients, one died after the onset of multiorgan failure.
      For the other nine, the mean time spent in the hospital was 9 days (range, 6-15
      days). CONCLUSIONS: Escherichia coli are developing new drug resistances. Early
      recognition of patients who harbor MDRO E. coli in their rectum or in the urine
      could be an important strategy for preventing sepsis. If a patient who has
      recently undergone transrectal prostate biopsy shows clinical signs of sepsis in
      the 48 h, a multiresistant E. coli infection must be suspected. The patient must
      be admitted urgently to the hospital, and carbapenem antibiotic therapy should be
      started.

PMID- 22371128
TI  - An integrated WebGIS framework for volunteered geographic information and social
      media in soil and water conservation.
AB  - Volunteered geographic information and social networking in a WebGIS has the
      potential to increase public participation in soil and water conservation,
      promote environmental awareness and change, and provide timely data that may be
      otherwise unavailable to policymakers in soil and water conservation management.
      The objectives of this study were: (1) to develop a framework for combining
      current technologies, computing advances, data sources, and social media; and (2)
      develop and test an online web mapping interface. The mapping interface
      integrates Microsoft Silverlight, Bing Maps, ArcGIS Server, Google Picasa Web
      Albums Data API, RSS, Google Analytics, and Facebook to create a rich user
      experience. The website allows the public to upload photos and attributes of
      their own subdivisions or sites they have identified and explore other
      submissions. The website was made available to the public in early February 2011
      at http://www.AbandonedDevelopments.com and evaluated for its potential long-term
      success in a pilot study.

PMID- 22371129
TI  - Contributions of private landowners to the conservation of the gopher tortoise
      (Gopherus polyphemus).
AB  - Private landowners play a pivotal role in determining whether or not rare species
      persist in regions where privately owned land is extensive. The range of the
      gopher tortoise (Gopherus polyphemus) is confined to the Southeastern U.S., a
      region predominantly under private ownership, and thus the status of this species
      is largely dependent upon land management decisions made by private landowners.
      We sent an anonymous mail survey to 2,584 individuals to examine factors
      affecting gopher tortoise occurrence on private lands in Mississippi (adjusted
      response rate of 23%). Few respondents (19%) reported currently having tortoises
      on their property, although many had them in the past (30%). Tortoises were
      persisting primarily on larger properties with longleaf pine that were not
      managed chiefly for timber production. In general, respondents were largely
      unaware of habitat requirements of tortoises or effects of various land
      management practices on them, and few reported using management techniques that
      benefit tortoises, such as prescribed burning. Most respondents (57%) knew of
      wildlife incentive programs, but were hesitant to enroll because they did not
      want to commit to managing their property in a particular manner (34%). We
      suggest actions that could improve the likelihood of tortoise persistence in this
      region, as well as changes that could be made to incentive programs to increase
      landowner participation. These suggestions should be relevant to the conservation
      of other rare species on private lands in other regions.

PMID- 22371130
TI  - Drug development and clinical trials--the path to an approved cancer drug.
AB  - Advances in our understanding of cancer biology have led to the discovery of a
      spectrum of new therapeutic targets. However, despite remarkable progress in the
      identification and characterization of novel mechanisms of the oncogenic process,
      the success rate for approval of oncology drugs remains low relative to other
      therapeutic areas. Innovative preclinical and clinical approaches, such as the
      use of advanced genomic technologies, as well as branched adaptive clinical trial
      designs, have the potential to accelerate the development and approval of highly
      effective oncology drugs, along with a matching diagnostic test to identify those
      patients most likely to benefit from the new treatment. To maximize the
      effectiveness of these new strategies, close collaboration between academic,
      industry, and regulatory agencies will be required. In this Review, we highlight
      new approaches in preclinical and clinical drug development that will help
      accelerate approval of drugs, and aim to provide more-effective treatments
      alongside companion diagnostic tests to ensure the right treatment is given to
      the right patient.

PMID- 22371131
TI  - Gynecological cancer: First-line bevacizumab for ovarian cancer--new standard of
      care?

PMID- 22371132
TI  - Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast
      cancer.
AB  - Mature outcomes from adjuvant endocrine therapy trials in estrogen receptor
      positive breast cancer have enabled comparisons with neoadjuvant clinical trials
      that have parallel randomizations of treatment in terms of the response of
      disseminated disease versus the local response within the breast. Imprecise end
      points, such as 'clinical response', have produced inconsistent results regarding
      the relationship between neoadjuvant and adjuvant endocrine therapy outcomes.
      However, the proliferation marker Ki-67, measured during neoadjuvant treatment,
      has predicted accurately and consistently the results of much larger studies in
      the adjuvant setting. In this Review, we summarize these trials and discuss the
      implications for the design of future adjuvant endocrine therapy trials. We
      conclude that there is sufficient evidence supporting the view that the degree of
      Ki-67 suppression is a reliable short-term surrogate for the adjuvant potential
      of endocrine drugs, at least in postmenopausal women. We propose that adjuvant
      endocrine therapy trials should only be conducted once adequately-powered
      neoadjuvant studies have indicated superior Ki-67 suppression in patients
      receiving experimental endocrine treatment versus the standard treatment.

PMID- 22371133
TI  - Genetics: Gene fusion power.

PMID- 22371134
TI  - Palliative care: ASCO provisional clinical opinion.

PMID- 22371135
TI  - Gastrointestinal cancer: Adjuvant chemotherapy after D2 gastrectomy for gastric
      cancer.

PMID- 22371136
TI  - Pediatrics: Chemotherapy exposure during pregnancy--good news.

PMID- 22371137
TI  - The mystery of C. elegans aging: an emerging role for fat. Distant parallels
      between C. elegans aging and metabolic syndrome?
AB  - New C. elegans studies imply that lipases and lipid desaturases can mediate
      signaling effects on aging. But why might fat homeostasis be critical to aging?
      Could problems with fat handling compromise health in nematodes as they do in
      mammals? The study of signaling pathways that control longevity could provide the
      key to one of the great unsolved mysteries of biology: the mechanism of aging.
      But as our view of the regulatory pathways that control aging grows ever clearer,
      the nature of aging itself has, if anything, grown more obscure. In particular,
      focused investigations of the oxidative damage theory have raised questions about
      an old assumption: that a fundamental cause of aging is accumulation of molecular
      damage. Could fat dyshomeostasis instead be critical?

PMID- 22371138
TI  - The axial stability of the femur after harvest of the medial femoral condyle
      corticocancellous flap: a biomechanical study of composite femur models.
AB  - PURPOSE: Free bone or periosteal flaps from the medial femoral condyle are being
      employed for treatment of recalcitrant nonunions. When harvested in a
      corticocancellous fashion, these flaps have the potential to compromise the
      stability of the femur. This study is designed to test the axial stability of the
      femur after harvest of corticocancellous flaps using a standardized composite
      femur model. METHODS: Corticocancellous defects of standardized width and depth
      (2 cm * 1 cm) were designed with increasing length (3-cm intervals extending from
      3 to 24 cm) over the medial femoral condyle of five composite femur models. After
      harvest of each corticocancellous block, the femur was subjected to an axial
      force of 9100 N loaded and unloaded over one second using a Mini-Bionix load
      frame. During the application of force, load and deformation data were collected
      from the load cell and linear variable differential transducer. To determine
      changes in stiffness or deformation with increasing flap sizes, analysis of
      variance with repeated measures was used. If the main effect was found to be
      significant, a Tukey's test was used to determine differences between specific
      flap sizes. RESULTS: There were no femur fractures in any femurs for any flap
      size. Deformation during load increased as the size of the flap increased (2.19
      mm +/- 0.062 mm for the 3-cm flap defect) to (2.33 mm +/- 0.113 mm for the 24-cm
      flap defect). Post-hoc testing of deformation shows a statistically significant
      difference only between the 3-cm flap defect and the 15-cm flap defect (2.19 vs.
      2.30 mm) (P = 0.002). The range of stiffness is between 4,339 and 4,697 N mm(-1)
      . Stiffness tends to decrease significantly (P < 0.001) with increasing flap
      size. Harvest of flap sizes greater or equal than 9 cm results in significantly
      lower stiffness compared to the 3-cm flap. CONCLUSIONS: In this composite femur
      model, when stressed with supraphysiologic forces, the femur retains its axial
      stability even after harvest of large corticocancellous flaps from its medial
      aspect. Statistical significance detected in deformation and stiffness may not be
      clinically relevant if the femur does not fracture after flap harvest. Such was
      the case in this experiment. The possibility exists of safely harvesting large
      flaps from this donor site. Corticocancellous flaps from the medial aspect of the
      femur may serve as an alternative to standard flaps used in medium and large
      osseous reconstructions. The size of flap that can be safely raised without
      compromising the stability of the femur has not yet been delineated.

PMID- 22371139
TI  - The serological profile of early-onset and persisting post-cardiac surgery
      thrombocytopenia complicated by "true" heparin-induced thrombocytopenia.

PMID- 22371140
TI  - Dependence of smooth muscle tone upon pulsatility in the iliac artery of the
      anaesthetised pig.
AB  - The aim of the study was to examine features of the myogenic response of a
      conduit artery to the presence and absence of pulsatile pressure. The iliac
      arteries of 16 anaesthetised pigs (10 in control conditions, 6 under sympathetic
      blockade) were instrumented with flowmeter, sonomicrometry crystals for diameter
      measurement, a micro-tip manometer for pressure measurement and snares placed
      proximally and distally to the crystals to isolate a test segment from the
      remainder of the arterial system. When the snares were tightened to occlude the
      test segment, systemic arterial pressure remained constant. There was a large
      shift in the pressure-diameter relationship, in that there was a rapid decline in
      test segment pressure for the same diameter. This indicated arterial wall smooth
      muscle relaxation in response to removal of pulsatility of arterial pressure. The
      difference in mean pressure between pulsatility present and absent was
      significant (p < 0.0001, paired t test, n = 10). Before proximal and distal
      occlusion, test segment pressure was (mean +/- SD) 92.26 +/- 12.39 mmHg, whereas
      after distal and proximal occlusion at the same diameter, it was 42.34 +/- 10.87
      mmHg. We conclude that in the presence of pulsatile pressure, there is a large
      proportion of arterial wall smooth muscle tone related to stretch of the arterial
      wall during the cardiac cycle, indicating that, under normal pulsatile pressure
      conditions, much of the normal tone can be attributed to the pulsatile component
      of the arterial myogenic response.

PMID- 22371141
TI  - Protein kinase C delta contributes to increase in EP3 agonist-induced contraction
      in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats.
AB  - Prostaglandin E(2) (PGE(2)), an important and ubiquitously present vasoactive
      eicosanoid, may either constrict or dilate systemic vascular beds. However,
      little is known about the vascular contractile responsiveness to and signaling
      pathways for PGE(2) at the chronic stage of type 2 diabetes. We hypothesized that
      PGE(2)-induced arterial contraction is augmented in type 2 diabetic Goto-Kakizaki
      (GK) rats via the protein kinase Cdelta (PKCdelta) pathway. Here, we investigated
      the vasoconstrictor effects of PGE(2) and of sulprostone (EP1-/EP3-receptor
      agonist) in rings cut from superior mesenteric arteries isolated from GK rats (37
      44 weeks old). In arteries from GK rats (vs. those from age-matched Wistar rats),
      examined in the presence of a nitric oxide synthase inhibitor: 1) the PGE(2)- and
      sulprostone-induced vasocontractions (which were not blocked by the selective EP1
      receptor antagonist sc19220) were enhanced, and these enhancements were
      suppressed by rottlerin (selective PKCdelta inhibitor) but not by Go6976
      (selective PKCalpha/beta inhibitor); 2) the sulprostone-stimulated
      phosphorylation of PKCdelta (at Thr(505)), which yields an active form, was
      increased and 3) sulprostone-stimulated caldesmon phosphorylations, which are
      related to isometric force generation in smooth muscle, were increased. The
      protein expression of EP3 receptor in superior mesenteric arteries was similar
      between the two groups of rats. Our data suggest that the diabetes-related
      enhancement of EP3 receptor-mediated vasocontraction results from activation of
      the PKCdelta pathway. Alterations in EP3 receptor-mediated vasocontraction may be
      important factors in the pathophysiological influences over arterial tone that
      are present in diabetic states.

PMID- 22371142
TI  - Development and application of SINE-based markers for genotyping of potato
      varieties.
AB  - Potato variety discrimination based on morphological traits is laborious and
      influenced by the environment, while currently applied molecular markers are
      either expensive or time-consuming in development or application. SINEs, short
      interspersed nuclear elements, are retrotransposons with a high copy number in
      plant genomes representing a potential source for new markers. We developed a
      marker system for potato genotyping, designated inter-SINE amplified polymorphism
      (ISAP). Based on nine potato SINE families recently characterized (Wenke et al.
      in Plant Cell 23:3117-3128, 2011), we designed species-specific SINE primers.
      From the resulting 153 primer combinations, highly informative primer sets were
      selected for potato variety analysis regarding number of bands, quality of the
      banding pattern, and the degree of polymorphism. Fragments representing ISAPs can
      be separated by conventional agarose gel electrophoresis; however, automation
      with a capillary sequencer is feasible. Two selected SINE families, SolS-IIIa and
      SolS-IV, were shown to be highly but differently amplified in Solanaceae,
      Solaneae tribe, including wild and cultivated potatoes, tomato, and eggplant.
      Fluorescent in situ hybridization demonstrated the genome-wide distribution of
      SolS-IIIa and SolS-IV along potato chromosomes, which is the basis for genotype
      discrimination and differentiation of somaclonal variants by ISAP markers.

PMID- 22371143
TI  - In vitro mesothelial clearance assay that models the early steps of ovarian
      cancer metastasis.
AB  - Ovarian cancer is the fifth leading cause of cancer related deaths in the United
      States(1). Despite a positive initial response to therapies, 70 to 90 percent of
      women with ovarian cancer develop new metastases, and the recurrence is often
      fatal(2). It is, therefore, necessary to understand how secondary metastases
      arise in order to develop better treatments for intermediate and late stage
      ovarian cancer. Ovarian cancer metastasis occurs when malignant cells detach from
      the primary tumor site and disseminate throughout the peritoneal cavity. The
      disseminated cells can form multicellular clusters, or spheroids, that will
      either remain unattached, or implant onto organs within the peritoneal cavity(3)
      (Figure 1, Movie 1).     All of the organs within the peritoneal cavity are lined
      with a single, continuous, layer of mesothelial cells(4-6) (Figure 2). However,
      mesothelial cells are absent from underneath peritoneal tumor masses, as revealed
      by electron micrograph studies of excised human tumor tissue sections(3,5-7)
      (Figure 2). This suggests that mesothelial cells are excluded from underneath the
      tumor mass by an unknown process.     Previous in vitro experiments demonstrated
      that primary ovarian cancer cells attach more efficiently to extracellular matrix
      than to mesothelial cells(8), and more recent studies showed that primary
      peritoneal mesothelial cells actually provide a barrier to ovarian cancer cell
      adhesion and invasion (as compared to adhesion and invasion on substrates that
      were not covered with mesothelial cells)(9,10). This would suggest that
      mesothelial cells act as a barrier against ovarian cancer metastasis. The
      cellular and molecular mechanisms by which ovarian cancer cells breach this
      barrier, and exclude the mesothelium have, until recently, remained unknown.    
      Here we describe the methodology for an in vitro assay that models the
      interaction between ovarian cancer cell spheroids and mesothelial cells in vivo
      (Figure 3, Movie 2). Our protocol was adapted from previously described methods
      for analyzing ovarian tumor cell interactions with mesothelial monolayers(8-16),
      and was first described in a report showing that ovarian tumor cells utilize an
      integrin -dependent activation of myosin and traction force to promote the
      exclusion of the mesothelial cells from under a tumor spheroid(17).  This model
      takes advantage of time-lapse fluorescence microscopy to monitor the two cell
      populations in real time, providing spatial and temporal information on the
      interaction. The ovarian cancer cells express red fluorescent protein (RFP) while
      the mesothelial cells express green fluorescent protein (GFP). RFP-expressing
      ovarian cancer cell spheroids attach to the GFP-expressing mesothelial monolayer.
      The spheroids spread, invade, and force the mesothelial cells aside creating a
      hole in the monolayer. This hole is visualized as the negative space (black) in
      the GFP image. The area of the hole can then be measured to quantitatively
      analyze differences in clearance activity between control and experimental
      populations of ovarian cancer and/ or mesothelial cells. This assay requires only
      a small number of ovarian cancer cells (100 cells per spheroid X 20-30 spheroids
      per condition), so it is feasible to perform this assay using precious primary
      tumor cell samples. Furthermore, this assay can be easily adapted for high
      throughput screening.

PMID- 22371144
TI  - Occult primary medullary thyroid carcinoma presenting with pituitary and parotid
      metastases: case report and review of the literature.

PMID- 22371145
TI  - Molecular biology of Pasteurella multocida toxin.
AB  - Pasteurella multocida toxin (PMT) is the causative agent of progressive atrophic
      rhinitis in swine. The 146 kDa single-chain toxin harbours discrete domains
      important for receptor binding, internalisation and biological activity. The
      molecular basis of the toxin's activity is the deamidation of a specific
      glutamine residue in the alpha-subunit of heterotrimeric G proteins. This results
      in an inhibition of the inherent GTPase activity leading to a constitutively
      active phenotype of the G protein. Due to the ability of the toxin to act on
      various families of heterotrimeric G proteins, a large subset of signal
      transduction pathways is stimulated.

PMID- 22371146
TI  - Looking beyond maternal sensitivity: mother-child correlates of attachment
      security among children with intellectual disabilities in urban India.
AB  - This study examined correlates of attachment security among children with
      intellectual disabilities in urban India. Survey and observational data were
      gathered from 47 children, mothers, and teachers on children's attachment
      security, adaptive functioning, and mother-child emotional availability. The data
      were analyzed to examine whether child emotional availability mediates the links
      between maternal emotional availability and child attachment security, and
      between child functioning and attachment security. The results supported full
      mediation, indicating that children's emotional availability was a primary
      mechanism through which maternal emotional availability and child functioning
      were linked to attachment security among children in our sample. The study
      findings are discussed in the context of implications for family interventions
      and research on socio-emotional development among children with intellectual
      disabilities.

PMID- 22371147
TI  - Factor structure of the Children's Behavior Questionnaire in children with
      Williams syndrome.
AB  - To examine the factor structure of temperament in 5-10-year-olds with Williams
      syndrome, an exploratory factor analysis was conducted on the responses of
      parents of 192 children on the children's behavior questionnaire. Four factors
      were identified. Two corresponded to factors reported for typically developing
      children: effortful control and extraversion/surgency and two corresponded to the
      temperament constructs of withdrawal/inhibition and irritability/frustration and
      activity, observed in typically developing infants. Parents of 109 of the 192
      participants also completed the anxiety disorders interview schedule, parent
      version. Children with an anxiety disorder other than specific phobia differed
      significantly from children without an anxiety disorder on all factors except
      extraversion/surgency. Children with attention deficit hyperactivity disorder
      (ADHD) differed significantly from children without ADHD on effortful control and
      extraversion/surgency.

PMID- 22371150
TI  - Characterization of hemicellulases from thermophilic fungi.
AB  - The thermophilic fungi Thermomyces lanuginosus, Malbranchea cinnamomea,
      Myceliophthora fergusii and the thermotolerant Aspergillus terreus were
      cultivated on various carbon sources, and hemicellulolytic and cellulolytic
      enzyme profiles were evaluated. All fungi could grow on locust bean galactomannan
      (LBG), Solka floc, wheat bran and pectin, except T. lanuginosus, which failed to
      utilize LBG for growth. Different levels of cellulase and hemicellulase
      activities were produced by these fungal strains. Depending on the carbon source,
      variable ratios of thermostable hydrolytic enzymes were obtained, which may be
      useful in various applications. All strains were found to secrete xylanolytic and
      mannanolytic enzymes. Generally, LBG was the most efficient carbon source to
      induce mannanase activities, although T. lanuginosus was able to produce
      mannanase only on wheat bran as a carbon source. Xylanolytic activities were
      usually highest on wheat bran medium, but in contrast to other investigated
      fungi, xylanase production by M. fergusii was enhanced on pectin medium.
      Preliminary thermostability screening indicated that among the investigated
      species, thermotolerant glycosidases can be found. Some of the accessory
      activities, including the alpha-arabinosidase activity, were surprisingly high.
      The capability of the produced enzymes to improve the hydrolysis of
      lignocellulosic pretreated substrate was evaluated and revealed potential for
      these enzymes.

PMID- 22371149
TI  - G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor
      interactions.
AB  - The medicinal chemistry and pharmacology of the four subtypes of adenosine
      receptors (ARs) and the eight subtypes of P2Y receptors (P2YRs, activated by a
      range of purine and pyrimidine mono- and dinucleotides) has recently advanced
      significantly leading to selective ligands. X-ray crystallographic structures of
      both agonist- and antagonist-bound forms of the A(2A)AR have provided
      unprecedented three-dimensional detail concerning molecular recognition in the
      binding site and the conformational changes in receptor activation. It is
      apparent that this ubiquitous cell signaling system has implications for
      understanding and treating many diseases. ATP and other nucleotides are readily
      released from intracellular sources under conditions of injury and organ stress,
      such as hypoxia, ischemia, or mechanical stress, and through channels and
      vesicular release. Adenosine may be generated extracellularly or by cellular
      release. Therefore, depending on pathophysiological factors, in a given tissue,
      there is often a tonic activation of one or more of the ARs or P2YRs that can be
      modulated by exogenous agents for a beneficial effect. Thus, this field has
      provided fertile ground for pharmaceutical development, leading to clinical
      trials of selective receptor ligands as imaging agents or for conditions
      including cardiac arrhythmias, ischemia/reperfusion injury, diabetes, pain,
      thrombosis, Parkinson's disease, rheumatoid arthritis, psoriasis, dry eye
      disease, pulmonary diseases such as cystic fibrosis, glaucoma, cancer, chronic
      hepatitis C, and other diseases.

PMID- 22371151
TI  - Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy
      towards synthesis of isofagomine and related biologically important azasugars.
AB  - Synthesis of isofagomine has been achieved by implementation of aza-Claisen
      rearrangement of 2-C-hydroxymethyl glycals as a key step. The above rearrangement
      has also been utilized in the synthesis of biologically important
      polyhydroxylated piperidine frameworks such as isogalactofagomine, ent
      isogalactofagomine and their analogues and some other azasugars as glycosidase
      inhibitors.

PMID- 22371152
TI  - Interosseous membrane: The anatomic basis for combined ankle and common fibular
      (peroneal) nerve injuries.
AB  - Common fibular (peroneal) nerve palsy has many etiologies. A rare cause with a
      poorly understood pathophysiology is common fibular nerve palsy that follows an
      ankle injury. Since the original description of this pathologic entity a century
      ago, several mechanisms have been posited. We present two cases of common fibular
      nerve palsy following ankle injury. These cases provide anatomic and radiologic
      evidence to support a hypothesis that the interosseous membrane provides the
      anatomic basis for this combined pattern of injury. This theory unifies
      previously postulated mechanisms.

PMID- 22371153
TI  - The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and
      survival in advanced non-small-cell lung cancer patients treated with gemcitabine
      plus platinum.
AB  - PURPOSE: The GNAS1 gene is linked to proapoptotic signaling and correlates
      closely with clinical outcomes in many human cancers. The aim of this study was
      to evaluate whether the T393C polymorphism of the GNAS1 gene could be used as a
      chemotherapy sensitivity and prognosis predictive marker of advanced non-small
      cell lung cancer (NSCLC) treated with gemcitabine plus platinum (GP). METHODS: In
      this study, we performed the PCR-restriction fragment length polymorphism assay
      to examine the genotypes of the GNAS1 T393C polymorphism in 131 peripheral blood
      DNA specimens from advanced NSCLC patients with GP treatment. RESULTS: The
      frequencies of the CC, CT, and TT genotypes in 131 advanced NSCLC cases were
      25.2, 47.4, and 26.7%, respectively. The favorable TT genotype was significantly
      correlated with better overall survival (OS; P < 0.05) and longer progress-free
      survival (PFS; P < 0.05) compared with the CT or CC genotype. In the multivariate
      Cox proportional hazards model, the GNAS1 T393C polymorphism was independently
      associated with overall survival after adjusting the clinicopathological factors
      (P < 0.05). CONCLUSIONS: This study suggests that the TT genotype of the GNAS1
      T393C polymorphism could be an independent prognostic marker to predict
      chemotherapy sensitivity, favorable OS and PFS in advanced NSCLC patients with GP
      treatment.

PMID- 22371154
TI  - Effects of atorvastatin on plasma fibrin clot properties in apparently healthy
      individuals and patients with previous venous thromboembolism.

PMID- 22371155
TI  - Outcome of surgical treatment of pelvic osteosarcoma.
AB  - BACKGROUND AND OBJECTIVES: Surgical treatment of pelvic osteosarcoma is often
      challenging. The objective of this study was to assess the oncologic and
      functional outcome and the operation-related complications of patients with
      pelvic osteosarcoma who were treated in a single center in the past decade.
      METHODS: Nineteen patients underwent surgical procedures between June 2000 and
      June 2009. There were 11 males and 8 females with a mean age of 30 years.
      According to Enneking and Dunham pelvic classification system, there were: Type I
      3, Type I + IV-3, Type I + II-2, Type II + III-4, Type I + II+ III-1, Type III-1,
      and type I + II+ IV-5. All patients received chemotherapy. RESULTS: Local
      recurrence rate was 26.3% (5/19). The 5-year overall survival rate was 44.9%.
      Seventeen patients received reconstruction after tumor resection. The average
      MSTS 93 score was 18 (10-23) for the 11 patients with hemipelvic endoprosthetic
      reconstruction and 23 (20-25) for 6 patients with rod-screw reconstruction.
      Complication was found in 7 of 19 patients (36.8%). CONCLUSION: The oncological
      results of pelvic osteosarcoma are poor at best. Even with a higher complication
      rate, we believe restoration of pelvic ring continuity and hip joint mobility is
      reasonable option to achieve favorable functional outcomes in selected patients.

PMID- 22371156
TI  - Identifying the diversity and impact of holistic nursing scholarship.

PMID- 22371160
TI  - Thyroid function: Thyroid screening in pregnancy--no effect on child cognition?

PMID- 22371162
TI  - Collegiality and careerism trump critical questions and bold new ideas: a
      student's perspective and solution. The structure of scientific funding limits
      bold new ideas.
AB  - Funding agencies (and journals) seem to be discriminating against ideas that are
      contrary to the mainstream, leading to leading to the preferential funding of
      predictable and safe research over radically new ideas. To remedy this problem a
      restructuring of the scientific funding system is needed, e.g. by utilizing
      laymen--together with scientists--to evaluate grant proposals.

PMID- 22371159
TI  - Cardiovascular autonomic neuropathies as complications of diabetes mellitus.
AB  - Diabetic autonomic neuropathies are a heterogeneous and progressive disease
      entity and commonly complicate both type 1 and type 2 diabetes mellitus. Although
      the aetiology is not entirely understood, hyperglycaemia, insulin deficiency,
      metabolic derangements and potentially autoimmune mechanisms are thought to play
      an important role. A subgroup of diabetic autonomic neuropathy, cardiovascular
      autonomic neuropathy (CAN), is one of the most common diabetes-associated
      complications and is ultimately clinically important because of its correlation
      with increased mortality. The natural history of CAN is unclear, but is thought
      to progress from a subclinical stage characterized by impaired baroreflex
      sensitivity and abnormalities of spectral analysis of heart rate variability to a
      clinically apparent stage with diverse and disabling symptoms. Early diagnosis of
      CAN, using spectral analysis of heart rate variability or scintigraphic imaging
      techniques, might enable identification of patients at highest risk for the
      development of clinical CAN and, thereby, enable the targeting of intensive
      therapeutic approaches. This Review discusses methods for diagnosis,
      epidemiology, natural history and potential causes and consequences of CAN.

PMID- 22371161
TI  - Management of diabetes mellitus: is the pump mightier than the pen?
AB  - Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces
      HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM)
      compared with multiple daily insulin injections (MDI). The greatest reduction in
      HbA(1c) levels with CSII occurs in patients with the worst glycaemic control;
      therefore, the most appropriate and cost-effective use of CSII in adults with
      T1DM is in those who have continued, elevated HbA(1c) levels or disabling
      hypoglycaemic episodes with MDI (including the use of long-acting insulin
      analogues and structured patient education). The disadvantages of CSII include
      higher costs than MDI and the risk of ketosis in the event of pump failure. In
      children with T1DM, CSII may be used when MDI is considered impractical or
      inappropriate. Pumps are not generally recommended for patients with type 2
      diabetes mellitus but may improve control in some subgroups. A new generation of
      smaller insulin infusion pumps with an integrated cannula, called patch pumps,
      could improve uptake of CSII in general. The important clinical question is not
      whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII
      further improves glycaemic control when this control continues to be poor with
      MDI, and evidence exists that in most cases it does.

PMID- 22371163
TI  - Naming and categorizing objects: task differences modulate the polarity of
      semantic effects in the picture-word interference paradigm.
AB  - The picture-word interference paradigm is a prominent tool for studying lexical
      retrieval during speech production. When participants name the pictures,
      interference from semantically related distractor words has regularly been shown.
      By contrast, when participants categorize the pictures, facilitation from
      semantically related distractors has typically been found. In the extant studies,
      however, differences in the task instructions (naming vs. categorizing) were
      confounded with the response level: While responses in naming were typically
      located at the basic level (e.g., "dog"), responses were located at the
      superordinate level in categorization (e.g., "animal"). The present study avoided
      this confound by having participants respond at the basic level in both naming
      and categorization, using the same pictures, distractors, and verbal responses.
      Our findings confirm the polarity reversal of the semantic effects--that is,
      semantic interference in naming, and semantic facilitation in categorization.
      These findings show that the polarity reversal of the semantic effect is indeed
      due to the different tasks and is not an artifact of the different response
      levels used in previous studies. Implications for current models of language
      production are discussed.

PMID- 22371164
TI  - New considerations for the cognitive locus of impairment in the irrelevant-sound
      effect.
AB  - The finding that serial recall performance for visually presented items is
      impaired by concurrently presented task-irrelevant speech or sounds is referred
      to as the irrelevant-speech/-sound effect (ISE). Substantial evidence has
      indicated that the impairment of serial rehearsal can result in an ISE, and this
      may be explained by several models. The present series of experiments has
      demonstrated an ISE in surprise nonserial recognition tasks in which participants
      were unaware of the need to maintain a large number of visual items for a later
      memory test, suggesting that neither the rehearsal nor maintenance of order
      information is necessary for observing the ISE. This effect was observed for both
      steady-state and changing-state irrelevant sounds, suggesting that the present
      results do not derive from a confusion of order information, but instead provide
      evidence that identity representations can also be impaired by irrelevant sound.

PMID- 22371165
TI  - The role of phantom recollection in false recall.
AB  - Although high levels of phantom recollection (illusory vivid experience of the
      prior "presentation" of unpresented items) have been found for false recognition,
      little is known about phantom recollection in recall. We examined this issue with
      Deese/Roediger-McDermott lists using two paradigms: repeated recall and conjoint
      recall. High levels of phantom recollection were observed with both standard
      behavioral measures and the parameters of fuzzy-trace theory's dual-recall model.
      In addition, phantom recollection and the true recollection that accompanies
      presented items appear to involve different retrieval processes, because they
      were dissociated by manipulations such as number of recall tests and list
      strength.

PMID- 22371166
TI  - Semi-free radial forearm flap for head and neck reconstruction in vessel-depleted
      neck after radiotherapy or radical neck dissection.
AB  - BACKGROUND: Venous thrombosis is the main cause of radial forearm flap failure,
      especially when recipient vessels are compromised by prior radiation therapy or
      neck dissection. In such conditions, semi-free radial forearm flap (SF-RFF) can
      be performed to reduce this risk. PATIENTS AND METHOD: We reviewed all SF-RFF
      procedures performed in our institution for head and neck reconstruction. The
      flap was harvested as a conventional radial forearm flap but the cephalic vein
      was dissected along the arm up to the deltopectoral crease and used as the sole
      drainage vein. RESULT: Seven SF-RFFs were harvested for head and neck
      reconstructions. The dissection of the cephalic vein lasted less than 25 min in
      all cases. No flap loss or thrombosis was observed. CONCLUSION: The SF-RFF is a
      reliable and versatile procedure for facial, oral, or larynx reconstruction. This
      hybrid version of the radial forearm free flap is particularly appropriate when
      no suitable recipient veins are available as a result of radiation or prior
      surgery.

PMID- 22371167
TI  - Phase II trial of concomitant neoadjuvant chemotherapy with oxaliplatin and
      capecitabine and intensity-modulated radiotherapy (IMRT) in rectal cancer.
AB  - INTRODUCTION AND PURPOSE: The purposes of this study are to evaluate the activity
      and safety of preoperative intensity-modulated radiotherapy and concurrent
      capecitabine and oxaliplatin (Xelox), the accuracy of preoperative magnetic
      resonance (MRI) for predicting pathologic results, and the correlation between
      carcinoembryonic antigen (CEA) and the existence of a pathologic complete
      response (pCR). PATIENTS AND METHODS: Twenty-seven patients (pt) with T3/T4N0/N+
      rectal cancer were included. Capecitabine was administered at 825 t.i.d. mg/m2
      the days of the radiotherapy (RT), and oxaliplatin was administered weekly at 50
      mg/m2. RT was planned to 50.4 Gy. Surgery was scheduled 6 to 8 weeks after
      completion of Xelox RT. Before the intervention, a pelvic MRI was performed and a
      CEA level was determined. RESULTS: After Xelox RT, 7 pt had pCR (26%), 2 pt
      progression disease, and 18 pt tumor downstaging. Presurgical MRI did not predict
      the pathological result in 21 pt. Main side effects were diarrhea grade (G) 3 in
      four pt, hand and foot G1 five Pt and G2 four pt. Paresthesias G1 ten pt, G2
      seven pt, and leukopenia six pt G1. Median RT dose was 49.7 Gy (47.5-50.4 Gy). At
      a mean follow-up of 22.5 months, four pt presented metastatis. Mean pretreatment
      CEA was 6.8 ng/mL (2.1-17.0). A difference statistically significant when
      compared pretreatment CEA with presurgical CEA (p < 0.001) was detected. We found
      a nadir of <5 ng/mL as significantly associated with pCR (p = 0.036). CONCLUSION:
      Preoperative chemoradiotherapy with oxaliplatin and capecitabine is safe and well
      tolerated, and offers an interesting ratio of pCR and of tumor downstaging.
      Presurgical CEA level should be studied as predictors of pCR.

PMID- 22371169
TI  - Functions and Biosynthesis of O-Acetylated Sialic Acids.
AB  - Sialic acids have a pivotal functional impact in many biological interactions
      such as virus attachment, cellular adhesion, regulation of proliferation, and
      apoptosis. A common modification of sialic acids is O-acetylation. O-Acetylated
      sialic acids occur in bacteria and parasites and are also receptor determinants
      for a number of viruses. Moreover, they have important functions in
      embryogenesis, development, and immunological processes. O-Acetylated sialic
      acids represent cancer markers, as shown for acute lymphoblastic leukemia, and
      they are known to play significant roles in the regulation of ganglioside
      mediated apoptosis. Expression of O-acetylated sialoglycans is regulated by
      sialic acid-specific O-acetyltransferases and O-acetylesterases. Recent
      developments in the identification of the enigmatic sialic acid-specific O
      acetyltransferase are discussed. 

PMID- 22371170
TI  - MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      demonstrated to be a valuable tool to investigate noncovalent interactions of
      biomolecules. The direct detection of noncovalent assemblies is often more
      troublesome than with electrospray ionization. Using dedicated sample preparation
      techniques and carefully optimized instrumental parameters, a number of
      biomolecule assemblies were successfully analyzed. For complexes dissociating
      under MALDI conditions, covalent stabilization with chemical cross-linking is a
      suitable alternative. Indirect methods allow the detection of noncovalent
      assemblies by monitoring the fading of binding partners or altered H/D exchange
      patterns.

PMID- 22371171
TI  - Olefination reactions of phosphorus-stabilized carbon nucleophiles.
AB  - A range of phosphorus-stabilized carbon nucleophiles have been employed for
      alkene synthesis with high chemo-, regio-, and stereoselectivity. The Wittig,
      Horner-Wadsworth-Emmons, Horner-Wittig, and Evans-Akiba reactions utilize
      phosphonium-, phosphonate-, phosphine oxide-, and pentacoordinated phosphorane
      stabilized carbanions as nucleophiles, respectively, to undergo olefination with
      aldehydes or ketones, and each of these transformations has its own advantages
      and limitations. Modifying the structures of these nucleophiles along with
      optimizing reaction conditions results in the formation of a wide variety of
      polysubstituted alkenes in a highly stereoselective manner. The olefination of
      imines with phosphonium ylides has recently emerged as a useful approach to tune
      the stereoselectivity for alkene synthesis. This review focuses on recent
      advances in the stereoselective olefination of phosphorus-stabilized carbon
      nucleophiles.

PMID- 22371172
TI  - Saliva, salivary gland, and hemolymph collection from Ixodes scapularis ticks.
AB  - Ticks are found worldwide and afflict humans with many tick-borne illnesses.
      Ticks are vectors for pathogens that cause Lyme disease and tick-borne relapsing
      fever (Borrelia spp.), Rocky Mountain Spotted fever (Rickettsia rickettsii),
      ehrlichiosis (Ehrlichia chaffeensis and E. equi), anaplasmosis (Anaplasma
      phagocytophilum), encephalitis (tick-borne encephalitis virus), babesiosis
      (Babesia spp.), Colorado tick fever (Coltivirus), and tularemia (Francisella
      tularensis) (1-8). To be properly transmitted into the host these infectious
      agents differentially regulate gene expression, interact with tick proteins, and
      migrate through the tick (3,9-13). For example, the Lyme disease agent, Borrelia
      burgdorferi, adapts through differential gene expression to the feast and famine
      stages of the tick's enzootic cycle (14,15). Furthermore, as an Ixodes tick
      consumes a bloodmeal Borrelia replicate and migrate from the midgut into the
      hemocoel, where they travel to the salivary glands and are transmitted into the
      host with the expelled saliva (9,16-19).    As a tick feeds the host typically
      responds with a strong hemostatic and innate immune response (11,13,20-22).
      Despite these host responses, I. scapularis can feed for several days because
      tick saliva contains proteins that are immunomodulatory, lytic agents,
      anticoagulants, and fibrinolysins to aid the tick feeding (3,11,20,21,23). The
      immunomodulatory activities possessed by tick saliva or salivary gland extract
      (SGE) facilitate transmission, proliferation, and dissemination of numerous tick
      borne pathogens (3,20,24-27). To further understand how tick-borne infectious
      agents cause disease it is essential to dissect actively feeding ticks and
      collect tick saliva. This video protocol demonstrates dissection techniques for
      the collection of hemolymph and the removal of salivary glands from actively
      feeding I. scapularis nymphs after 48 and 72 hours post mouse placement. We also
      demonstrate saliva collection from an adult female I. scapularis tick.

PMID- 22371173
TI  - Erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a
      myeloproliferative disease in mice.
AB  - The JAK2V617F mutation has been found in most cases of Ph-negative
      myeloproliferative neoplasms. Recent studies have shown that expression of
      Jak2V617F in the hematopoietic compartment causes marked expansion of erythroid
      progenitors and their transformation to cytokine-independence. To determine if
      erythroid progenitors are the target cells for induction and propagation of
      Jak2V617F-evoked myeloproliferative neoplasm, we used a conditional Jak2V617F
      knock-in mouse and an erythroid-lineage specific EpoRCre line. Erythroid-specific
      expression of heterozygous or homozygous Jak2V617F resulted in a polycythemia
      like phenotype characterized by increase in hematocrit and hemoglobin, increased
      red blood cells, erythropoietin-independent erythroid colonies and splenomegaly.
      Transplantation of Jak2V617F-expressing erythroid progenitors from the diseased
      mice into secondary recipients could not propagate the disease. Our results
      suggest that erythroid lineage-restricted expression of Jak2V617F is sufficient
      to induce a polycythemia-like disease in a gene-dose dependent manner. Jak2V617F
      mutation, however, does not confer leukemia stem cell-like properties to
      erythroid progenitors.

PMID- 22371174
TI  - Hematopoietic stem cell transplantation improves the high incidence of
      neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological
      enzyme replacement therapy.
AB  - BACKGROUND: Mucopolysaccharidosis type I is caused by deficiency of alpha-L
      iduronidase. Currently available treatment options include an allogeneic
      hematopoietic stem cell transplant and enzyme replacement therapy. Exogenous
      enzyme therapy appears promising but the benefits may be attenuated, at least in
      some patients, by the development of an immune response to the delivered enzyme.
      The incidence and impact of alloimmune responses in these patients remain
      unknown. DESIGN AND METHODS: We developed an immunoglobulin G enzyme-linked
      immunosorbent assay as well as in vitro catalytic enzyme inhibition and cellular
      uptake inhibition assays and quantified enzyme inhibition by allo-antibodies. We
      determined the impact of these antibodies in eight patients who received enzyme
      therapy before and during hematopoietic stem cell transplantation. In addition,
      20 patients who had previously received an allogeneic stem cell transplant were
      tested to evaluate this treatment as an immune tolerance induction mechanism.
      RESULTS: High titer immune responses were seen in 87.5% (7/8) patients following
      exposure to alpha-L-iduronidase. These patients exhibited catalytic enzyme
      inhibition (5/8), uptake inhibition of catalytically active enzyme (6/8) or both
      (4/8). High antibody titers generally preceded elevation of previously described
      biomarkers of disease progression. The median time to development of immune
      tolerance was 101 days (range, 26-137) after transplantation. All 20 patients,
      including those with mixed chimerism (22%), tested 1 year after transplantation
      were tolerized despite normal enzyme levels. CONCLUSIONS: We found a high
      incidence of neutralizing antibodies in patients with mucopolysaccharidosis type
      I treated with enzyme replacement therapy. We also found that allogeneic
      hematopoietic stem cell transplantation was an effective and rapid immune
      tolerance induction strategy.

PMID- 22371175
TI  - Estradiol increases hematopoietic stem and progenitor cells independent of its
      actions on bone.
AB  - Hematopoietic stem and progenitor cells reside in vascular and endosteal niches
      in the bone marrow. Factors affecting bone remodeling were reported to influence
      numbers and mobilization of hematopoietic stem cells. We therefore analyzed the
      effects of estradiol acting anabolic on bone integrity. Here we observe that
      estradiol increases progenitor cell numbers in the vascular but not in the
      endosteal compartment independent of its estrogen receptor alpha-dependent
      anabolic bone effects. Hematopoietic progenitors capable of reconstituting
      lethally irradiated mice are increased by enhanced cell cycle entry, leading to a
      diminished long-term reconstitution potential after serial transplantation. We
      demonstrate that estradiol action on stromal cells potently favors hematopoietic
      progenitor/stem cell frequency accompanied by enhanced expression of cell
      adhesion molecules. Finally, estradiol treatment enhances retention of
      hematopoietic stem cells in the vascular niche of the bone marrow. We describe
      for the first time the mechanism of estrogen action on hematopoietic stem and
      progenitor cells.

PMID- 22371176
TI  - Pontin is essential for murine hematopoietic stem cell survival.
AB  - Pontin is a highly conserved DNA helicase/ATPase which is a component of several
      macromolecular complexes with functions that include DNA repair, telomere
      maintenance and tumor suppression. While Pontin is known to be essential in
      yeast, fruit flies and frogs, its physiological role in mammalian organisms
      remains to be determined. We here find that Pontin is highly expressed in
      embryonic stem cells and hematopoietic tissues. Through germline inactivation of
      Ruvbl1, the gene encoding Pontin, we found it to be essential for early
      embryogenesis, as Ruvbl1 null embryos could not be recovered beyond the
      blastocyst stage where proliferation of the pluripotent inner cell mass was
      impaired. Conditional ablation of Ruvbl1 in hematopoietic tissues led to bone
      marrow failure. Competitive repopulation experiments showed that this included
      the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore,
      essential for the function of both embryonic pluripotent cells and adult
      hematopoietic stem cells.

PMID- 22371177
TI  - Persistent poor long-term prognosis of allogeneic hematopoietic stem cell
      transplant recipients surviving invasive aspergillosis.
AB  - BACKGROUND: Voriconazole treatment increases early survival of allogeneic
      hematopoietic stem cell transplant recipients with invasive aspergillosis. We
      investigated whether this survival advantage translates into an increased long
      term survival. DESIGN AND METHODS: This retrospective study involved all patients
      with an invasive aspergillosis diagnosis transplanted between September 1997 and
      December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point
      was survival up to 36 months. Survival analysis before and after 12 weeks, as
      well as cumulative incidence analysis in a competing risk framework, were used to
      assess the effect of voriconazole treatment and other factors on mortality.
      RESULTS: Among 87 patients, 42 received first-line voriconazole and 45 received
      another antifungal agent. Median survival time was 2.6 months and survival rate
      at 36 months was 18%. Overall, there was a significant difference in the survival
      rates of the two groups. Specifically, there was a dramatic difference in
      survival rates up to ten months post-aspergillosis diagnosis but no significant
      difference after this time. Over the first 36 months as a whole, no significant
      difference in survival rate was observed between the two groups. First-line
      voriconazole significantly reduced aspergillosis-attributable mortality. However,
      first-line voriconazole patients experienced a significantly higher probability
      of death from a non-aspergillosis-attributable cause. CONCLUSIONS: Although the
      prognosis for invasive aspergillosis after stem cell transplantation has
      dramatically improved with the use of voriconazole, this major advance in care
      does not translate into increased long-term survival for these severely
      immunocompromised patients.

PMID- 22371178
TI  - Targeting intratumoral B cells with rituximab in addition to CHOP in
      angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.
AB  - BACKGROUND: In angioimmunoblastic T-cell lymphoma, symptoms linked to B
      lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts,
      often infected by Epstein-Barr virus, are found in tumor tissues. We postulated
      that the disruption of putative B-T interactions and/or depletion of the Epstein
      Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could
      improve the clinical outcome produced by conventional chemotherapy. DESIGN AND
      METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study,
      with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B
      blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were
      fully characterized at diagnosis and were correlated with clinical outcome.
      RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With
      a median follow-up of 24 months, the 2-year progression-free survival rate was
      42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%).
      The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells
      (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes
      (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite
      peripheral Epstein-Barr virus clearance after treatment, the viral load at
      diagnosis (>100 copy/MUg DNA) was associated with shorter progression-free
      survival (P=0.06). CONCLUSIONS: We report here the results of the first clinical
      trial targeting both the neoplastic T cells and the microenvironment-associated
      CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear
      benefit of adding rituximab to conventional chemotherapy. A strong relationship,
      not previously described, between circulating Epstein-Barr virus and circulating
      tumor cells is highlighted.

PMID- 22371179
TI  - Arachidonic acid depletion extends survival of cold-stored platelets by
      interfering with the [glycoprotein Ibalpha--14-3-3zeta] association.
AB  - BACKGROUND: Cold storage of platelets reduces bacterial growth and preserves
      their hemostatic properties better than current procedures do. However, storage
      at 0 degrees C induces [14-3-3zeta-glycoprotein Ibalpha] association, 14-3-3zeta
      release from phospho-Bad, Bad activation and apoptosis. DESIGN AND METHODS: We
      investigated whether arachidonic acid, which also binds 14-3-3zeta, contributes
      to coldinduced apoptosis. RESULTS: Cold storage activated P38-mitogen-activated
      protein kinase and released arachidonic acid, which accumulated due to cold
      inactivation of cyclooxygenase-1/thromboxane synthase. Accumulated arachidonic
      acid released 14-3-3zeta from phospho-Bad and decreased the mitochondrial
      membrane potential, which are steps in the induction of apoptosis. Addition of
      arachidonic acid did the same and its depletion made platelets resistant to cold
      induced apoptosis. Incubation with biotin-arachidonic acid revealed formation of
      an [arachidonic acid-14-3-3zeta-glycoprotein Ibalpha] complex. Indomethacin
      promoted complex formation by accumulating arachidonic acid and released 14-3
      3zeta from cyclo-oxygenase-1. Arachidonic acid depletion prevented the cold
      induced reduction of platelet survival in mice. CONCLUSIONS: We conclude that
      cold storage induced apoptosis through an [arachidonic acid-14-3-3zeta
      glycoprotein Ibalpha] complex, which released 14-3-3zeta from Bad in an
      arachidonic acid-dependent manner. Although arachidonic acid depletion reduced
      agonist-induced thromboxane A(2) formation and aggregation, arachidonic acid
      repletion restored these functions, opening ways to reduce apoptosis during
      storage without compromising hemostatic functions post-transfusion.

PMID- 22371180
TI  - Report from the European Myeloma Network on interphase FISH in multiple myeloma
      and related disorders.
AB  - The European Myeloma Network has organized two workshops on fluorescence in situ
      hybridization in multiple myeloma. The first aimed to identify specific
      indications and consensus technical approaches of current practice. A second
      workshop followed a quality control exercise in which 21 laboratories analyzed
      diagnostic cases of purified plasma cells for recurrent abnormalities. The
      summary report was discussed at the EHA Myeloma Scientific Working Group Meeting
      2010. During the quality control exercise, there was acceptable agreement on more
      than 1,000 tests. The conclusions from the exercise were that the primary
      clinical applications for FISH analysis were for newly diagnosed cases of MM or
      frank relapse cases. A range of technical recommendations included: 1) material
      should be part of the first draw of the aspirate; 2) samples should be sent at
      suitable times to allow for the lengthy processing procedure; 3) most
      importantly, PCs must be purified or specifically identified; 4) positive cut-off
      levels should be relatively conservative: 10% for fusion or break-apart probes,
      20% for numerical abnormalities; 5) informative probes should be combined to best
      effect; 6) in specialist laboratories, a single experienced analyst is considered
      adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test
      for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes
      should be available for clinically relevant abnormalities; 10) the clinical
      report should be expressed clearly and must state the percentage of PC involved
      and the method used for identification; 11) a retrospective European based FISH
      data bank linked to clinical data should be generated; and 12) prospective
      analysis should be centralized for upcoming trials based on the recommendations
      made. The European Myeloma Network aims to build on these recommendations to
      establish standards for a common European data base to define subgroups with
      prognostic significance.

PMID- 22371181
TI  - Mesenchymal stromal cells protect mantle cell lymphoma cells from spontaneous and
      drug-induced apoptosis through secretion of B-cell activating factor and
      activation of the canonical and non-canonical nuclear factor kappaB pathways.
AB  - BACKGROUND: There is increasing evidence that stromal cell interactions are
      required for the survival and drug resistance of several types of B-cell
      malignancies. There is relatively little information regarding the role of the
      bone marrow/lymphoid microenvironment in the pathogenesis of mantle cell
      lymphoma. In this study we investigated the interaction of primary mantle cell
      lymphoma cells with stromal cells in an ex vivo co-culture system. DESIGN AND
      METHODS: The murine stromal cell line MS-5 and human bone marrow mesenchymal
      stromal cells were each co-cultured with primary mantle cell lymphoma cells for
      up to 7 months. Mantle cell lymphoma cultures alone or combined with human
      stromal cells were analyzed for cell number, cell migration, nuclear factor
      kappaB activation and drug resistance. RESULTS: Co-culture of mantle cell
      lymphoma cells and human stromal cells results in the survival and proliferation
      of primary mantle cell lymphoma cells for at least 7 months compared to mantle
      cell lymphoma cells cultured alone. Mantle cell lymphoma-human stromal cell
      interactions resulted in activation of the B-cell activating factor/nuclear
      factor-kappaB signaling axis resulting in reduced apoptosis, increased mantle
      cell lymphoma migration and increased drug resistance. CONCLUSIONS: Direct mantle
      cell lymphoma-human stromal cell interactions support long-term expansion and
      increase the drug-resistance of primary mantle cell lymphoma cells. This is due
      in part to activation of the canonical and non-canonical nuclear factor kappaB
      pathways. We also demonstrated the ability of B-cell activating factor to augment
      CXCL12- and CXCL13-induced cell migration. Collectively, these findings
      demonstrate that human stromal cell-mantle cell lymphoma interactions play a
      pivotal role in the pathogenesis of mantle cell lymphoma and that analysis of
      mantle cell lymphoma-human stromal cell interactions may help in the
      identification of novel targets for therapeutic use.

PMID- 22371182
TI  - High D-dimer levels are associated with poor prognosis in cancer patients.
AB  - BACKGROUND: Systemic activation of hemostasis is frequently observed in cancer
      patients, even in the absence of thrombosis. Moreover, this activation has been
      implicated in tumor progression, angiogenesis and metastatic spread. Increased
      levels of D-dimer, which is a degradation product of cross-linked fibrin,
      indicate a global activation of hemostasis and fibrinolysis. DESIGN AND METHODS:
      In a prospective and observational cohort study, we assessed the prognostic value
      of D-dimer levels for overall survival and mortality risk in 1178 cancer patients
      included in the Vienna Cancer and Thrombosis Study (CATS). Patients were followed
      over 2 years at regular intervals until occurrence of symptomatic venous
      thromboembolism or death. D-dimer levels were measured with a quantitative D
      dimer latex agglutination assay RESULTS: The main solid tumors were malignancies
      of the lung (n=182), breast (n=157), lower gastrointestinal tract (n=133),
      pancreas (n=74), stomach (n=50), kidney (n=37), prostate (n=133), and brain
      (n=148); 201 of the patients had hematologic malignancies; 63 had other tumors.
      During a median follow-up of 731 days, 460 (39.0%) patients died. The overall
      survival probabilities for patients with D-dimer levels categorized into four
      groups based on the 1(st), 2(nd) and 3(rd) quartiles of the D-dimer distribution
      in the total study population were 88%, 82%, 66% and 53% after 1 year, and 78%,
      66%, 50% and 30% after 2 years, respectively (P<0.001). The univariate hazard
      ratio of D-dimer (per double increase) for mortality was 1.5 (95% confidence
      interval: 1.4-1.6, P<0.001) and remained increased in multivariable analysis
      including tumor subgroups, age, sex and venous thromboembolism. CONCLUSIONS: High
      D-dimer levels were associated with poor overall survival and increased mortality
      risk in cancer patients.

PMID- 22371183
TI  - Impaired expression of DICER, DROSHA, SBDS and some microRNAs in mesenchymal
      stromal cells from myelodysplastic syndrome patients.
AB  - Background Recent findings suggest that a specific deletion of Dicer1 in
      mesenchymal stromal cell-derived osteoprogenitors triggers several features of
      myelodysplastic syndrome in a murine model. Our aim was to analyze DICER1 and
      DROSHA gene and protein expression in mesenchymal stromal cells (the osteoblastic
      progenitors) obtained from bone marrow of myelodysplastic syndrome patients, in
      addition to microRNA expression profile and other target genes such as SBDS, a
      DICER1-related gene that promotes bone marrow dysfunction and myelodysplasia when
      repressed in a murine model. DESIGN AND METHODS: Mesenchymal stromal cells from
      33 bone marrow samples were evaluated. DICER, DROSHA and SBDS gene expression
      levels were assessed by real-time PCR and protein expression by Western blot.
      MicroRNA expresion profile was analyzed by commercial low-density arrays and some
      of these results were confirmed by individual real-time PCR. RESULTS: Mesenchymal
      stromal cells from myelodysplastic syndrome patients showed lower DICER1 (0.65+/
      0.08 vs. 1.91+/-0.57; P=0.011) and DROSHA (0.62+/-0.06 vs. 1.38+/-0.29; P=0.009)
      gene expression levels, two relevant endonucleases associated to microRNA
      biogenesis, in comparison to normal myelodysplastic syndrome. These findings were
      confirmed at protein levels by Western blot. Strikingly, no differences were
      observed between paired mononuclear cells from myelodysplastic syndrome and
      controls. In addition, mesenchymal stromal cells from myelodysplastic syndrome
      patients showed significant lower SBDS (0.63+/-0.06 vs. 1.15+/-0.28; P=0.021)
      gene expression levels than mesenchymal stromal cells from healthy controls.
      Furthermore, mesenchymal stromal cells from myelodysplastic syndrome patients
      showed an underlying microRNA repression compared to healthy controls. Real-time
      PCR approach confirmed that mir-155, miR-181a and miR-222 were down-expressed in
      mesenchymal stromal cells from myelodysplastic syndrome patients.  Conclusions
      This is the first description of an impaired microRNA biogenesis in human
      mesenchymal stromal cells from myelodysplastic syndrome patients, where DICER1
      and DROSHA gene and protein downregulation correlated to a gene and microRNA
      abnormal expression profile, validating the animal model results previously
      described.

PMID- 22371184
TI  - Evaluation of prognostic factors among patients with chronic graft-versus-host
      disease.
AB  - BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication
      after allogeneic stem cell transplantation with an adverse effect on both
      mortality and morbidity. In 2005, the National Institute of Health proposed new
      criteria for diagnosis and classification of chronic graft-versus-host disease
      for clinical trials. New sub-categories were recognized such as late onset acute
      graft-versus-host disease and overlap syndrome. DESIGN AND METHODS: We evaluated
      the prognostic impact of the new sub-categories as well as the clinical scoring
      system proposed by the National Institute of Health in a retrospective,
      multicenter study of 820 patients undergoing allogeneic stem cell transplantation
      between 2000 and 2006 at 3 different institutions. Patients were retrospectively
      categorized according to the National Institute of Health criteria from patients'
      medical histories. RESULTS: As far as the new sub-categories are concerned, in
      univariate analysis diagnosis of overlap syndrome adversely affected the outcome.
      Also, the number of organs involved for a cut-off value of 4 significantly
      influenced both cGVHD related mortality and survival. In multivariate analysis,
      in addition to NIH score, platelet count and performance score at the time of
      cGVHD diagnosis, plus gut involvement, significantly influenced outcome. These 3
      variables allowed us to develop a simple score system which identifies 4
      subgroups of patients with 84%, 64%, 43% and 0% overall survival at five years
      after cGVHD diagnosis (score 0: HR=15.96 (95% CI: 6.85-37.17), P<0.001; score 1:
      HR=5.47 (95% CI: 2.6-11.5), P<0.001; score 2: HR=2.8 (95% CI: 1.32-5.93),
      P=0.007). CONCLUSIONS: In summary, we have identified a powerful and simple tool
      to discriminate different subgroups of patients in terms of chronic graft-versus
      host disease related mortality and survival.

PMID- 22371186
TI  - The use of rivaroxaban for short- and long-term treatment of venous
      thromboembolism.
AB  - Venous thromboembolism (VTE) is a major healthcare concern and affects more than
      1.6 million individuals each year worldwide. Long-term complications include
      recurrent VTE, chronic thromboembolic pulmonary hypertension and post-thrombotic
      syndrome. Rivaroxaban is an oral, direct factor Xa inhibitor that has advantages
      over traditional VTE therapies, including minimal drug and food interactions and
      no requirement for routine coagulation monitoring. It is currently approved for
      VTE prevention in adult patients undergoing elective hip or knee replacement
      surgery. This review evaluates the potential clinical implications of the
      multicentre, randomised EINSTEIN studies (EINSTEIN DVT and EINSTEIN EXT), which
      investigated rivaroxaban for the treatment and prevention of recurrent VTE. In
      EINSTEIN DVT, rivaroxaban was non-inferior to the standard of care (enoxaparin
      plus a vitamin K antagonist) for recurrent VTE in patients with acute deep-vein
      thrombosis (DVT) without pulmonary embolism (PE). In EINSTEIN EXT, extended
      duration rivaroxaban had superior efficacy to placebo in patients with confirmed
      DVT or PE who had received 6-12 months of prior VTE treatment. Rivaroxaban was
      associated with an acceptable safety profile in both studies. The net clinical
      benefit (efficacy and safety endpoints combined) of rivaroxaban was significantly
      greater than its comparators. The EINSTEIN studies are the first demonstration
      that a single drug--rivaroxaban--can be effective for both the initial treatment
      of DVT and prevention of recurrent VTE. Moreover, the simple, once-daily oral
      administration of rivaroxaban could potentially improve adherence to extended
      duration VTE treatment compared with the current standard of care in individuals
      with confirmed DVT or PE.

PMID- 22371187
TI  - A novel glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter for expressing
      transgenes in the halotolerant alga Dunaliella salina.
AB  - A major challenge for efficient transgene expression in Dunaliella salina is to
      find strong endogenous promoters to drive the transgene expression. In the
      present study, a novel glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter
      was cloned and used to drive expressions of the bialaphos resistance (bar) gene
      and of the N-terminal fragment of human canstatin (Can-N). The results showed
      that the bar gene was transcribed by the GAPDH promoter and integrated into the
      genome of the transformants of D. salina. Furthermore, the PCR identification,
      Southern and western blots indicated that Can-N was expressed in transgenic D.
      salina, demonstrating that the promoter of the D. salina GAPDH gene is suitable
      for driving expression of heterologous genes in transgenic D. salina.

PMID- 22371188
TI  - In vivo pH imaging with (99m)Tc-pHLIP.
AB  - PURPOSE: A novel molecular imaging agent has been developed recently, which
      stains tissues of low extracellular pH [pH (low) insertion peptide, pHLIP((r))].
      A pH-dependent process of peptide folding and insertion into cell membranes has
      been found in vitro. Targeting of acidic solid tumours has been demonstrated in
      vivo using fluorescence and PET labels. Here, we present proof of feasibility
      studies of pHLIP with a single-photon emission computed tomography (SPECT) label,
      (99m)Tc-AH114567, with focus on preclinical efficacy and imageability.
      PROCEDURES: Lewis lung carcinoma, lymph node carcinoma of the prostate and
      prostate adenocarcinoma tumour xenografts were grown in mice and characterised by
      the angiogenesis marker (99m)Tc-NC100692 and by extracellular pH measurements
      with (31)P-MRS of 3-aminopropyl phosphonate. Biodistribution was assessed and
      CT/SPECT imaging performed. Oral administration of bicarbonate served as control.
      RESULTS AND CONCLUSION: Tc-AH114567 can be obtained via a robust synthesis with
      good radiolabelling profile and improved formulation. The tracer retains the pH
      dependent ability to insert into membranes and to target tumours with similar
      pharmacokinetics and efficacy that had been demonstrated earlier for pHLIP with
      optical or (64)Cu PET labels. Despite the inherent challenges of SPECT compared
      to optical and PET imaging, e.g., in terms of lower sensitivity, (99m)Tc-AH114567
      shows adequate image quality and contrast. The main development need for
      transitioning SPECT labelled pHLIP into the clinic is more rapid background
      signal reduction, which will be the focus of a subsequent optimisation study.

PMID- 22371189
TI  - Clinical relevance of induction triplet chemotherapy for esophageal cancer
      invading adjacent organs.
AB  - BACKGROUND AND OBJECTIVES: There is no consensus on treatment for esophageal
      cancer invading adjacent organs (T4), but induction multidrug chemotherapy may be
      a beneficial, especially when surgery is considered as adjuvant treatment.
      METHODS: We classified 169 patients with T4 esophageal cancer without distant
      metastasis into those undergoing chemotherapy using cisplatin and 5-FU (CF) plus
      adriamycin or CF plus docetaxel (79 patients) and those undergoing
      chemoradiotherapy using CF (90 patients). For the former group, chemoradiation
      was subsequently applied when surgical resection was not indicated. RESULTS:
      Thirty-four patients in the chemotherapy group (43.0%) received chemoradiotherapy
      following chemotherapy. Although the response rate tended to be higher in the
      chemoradiotherapy group, there was no significant difference in the response rate
      between the groups (63.3% vs. 68.9%). Esophageal perforation during treatment was
      more frequent among the chemoradiotherapy group than the chemotherapy group
      (16.7% vs. 6.3%, P=0.0379). The rate of surgical resection was consequently
      higher for the induction chemotherapy group compared to the chemoradiotherapy
      group (72.1% vs. 45.6%, P=0.0005). CONCLUSIONS: Induction triplet chemotherapy
      reduced esophageal perforation and increased the resectability of T4 esophageal
      cancers by combining second-line chemoradiotherapy. This strategy might increase
      the chance of curative resection for patients with T4 esophageal cancer.

PMID- 22371190
TI  - Care integration in the Patient Protection and Affordable Care Act: implications
      for behavioral health.
AB  - Individuals with co-occurring serious mental illness and substance use disorders
      experience a highly fragmented system of care, contributing to poor health
      outcomes and elevated levels of unmet treatment needs. Several elements in the
      health care reform law may address these issues by enhancing the integration of
      physical and behavioral health care systems. The purpose of this paper is to
      analyze these elements, which fall into three domains: increasing access,
      restructuring financing and reimbursement mechanisms, and enhancing
      infrastructure. We conclude with a consideration of the implementation challenges
      that lie ahead.

PMID- 22371191
TI  - Comments on "Determination of mercury, cadmium, lead, zinc, selenium and iron by
      ICP-OES in mushroom samples from around thermal power plant in Mugla, Turkey".
      doi:10.1007/s00128-011-0357-1.
AB  - In several articles on trace elements in mushrooms erroneous data were published
      on minerals sequestered in fruiting bodies. The biased analytical data published
      gave a false picture on the composition and nutritional value of mushrooms with
      respect to minerals. Wild mushrooms are relatively rich in trace elements and
      some species can hyperaccumulate certain metals. Selenium as reported in the
      referenced article is discussed in light of typical Se concentrations determined
      using validated methods as reported by other authors.

PMID- 22371192
TI  - Biodegradation of fipronil by Paracoccus sp. in different types of soil.
AB  - In the present studies potential of microorganisms isolated from the cotton
      fields was explored for the bioremediation of fipronil contaminated soils. The
      cultures of microbes were grown in Luria broth as shake culture maintained at 28
      degrees C. After that Dorn's broth enrichment culture supplemented with fipronil
      was used and isolated two bacterial cultures viz. Paracoccus sp. and Gamma
      Proteobacteria. The performance of both bacteria was evaluated for degradation of
      fipronil in soil. Paracoccus sp. was found better than the Gamma Proteobacteria
      as far as degradation of fipronil in soil is concerned. The samples of soil were
      extracted and cleaned up by following a standardized methodology. Fipronil was
      quantified by gas liquid chromatography and confirmed by gas chromatography mass
      spectrometer. The limit of quantification of fipronil was worked out to be 10 MUg
      kg(-1). By using this methodology, the mean recoveries of fipronil in different
      types of soil were found to be more than 85%. The residues of fipronil were found
      to persist only up to 10 days in soils fortified with fipronil @ 20 MUg kg(-1)
      and amended with Paracoccus sp. while in the soils fortified @ 80 MUg kg(-1)
      fipronil, residues persisted up to 20, 30 and 30 days in loamy sand, sandy loam
      and clay loam, respectively. Therefore, the use of Paracoccus sp. can further be
      explored for the bioremediation of fipronil contaminated soils.

PMID- 22371193
TI  - Using light and a molecular switch to 'lock' and 'unlock' the Diels-Alder
      reaction.
AB  - Light is used to 'gate' the Diels-Alder reaction using a photoresponsive
      dithienylfuran backbone and turn the reversibility of the Diels-Alder reaction
      'off' and 'on' at 100  degrees C. These features make the reported system an
      excellent candidate for developing the next generation of self-healing polymers
      and photothermal drug delivery vehicles.

PMID- 22371194
TI  - Parental smoking and children's attention to smoking cues.
AB  - Research has shown that children with smoking parents are more likely to initiate
      smoking than children with non-smoking parents. So far, these effects have been
      explained through genetic factors, modelling and norm-setting processes. However,
      it is also possible that parental smoking affects smoking initiation through
      automatic cognitive processes. Therefore, we examined whether children with a
      smoking parent focus longer, faster and more often on smoking cues. The children
      were given two movie clips to watch, during which their attention to smoking cues
      was assessed with eye-tracking technology. Results showed that children with a
      smoking parent focused more often and longer on smoking cues compared with
      children with non-smoking parents. No correlations between attentional bias and
      explicit smoking cognitions were found. In conclusion, results suggest that
      parental smoking affects children's attention to smoking cues. These findings may
      indicate that parental smoking instigates automatic cognitive processes in
      children who have not experimented with smoking, and possibly even before
      explicit smoking cognitions become more favourable.

PMID- 22371195
TI  - Genomics: How pervasive are defective genes?

PMID- 22371196
TI  - Ageing: MicroRNA tunes ageing pathway in flies.

PMID- 22371197
TI  - Development: Robust but responsive protein gradients.

PMID- 22371198
TI  - Informational affordances: evidence of acquired perception-action sequences for
      information extraction.
AB  - Visual objects can automatically prime actions allowing efficient interaction
      with them. The present study examined whether object perception can automatically
      prime actions leading to efficient information extraction. Participants in
      Experiment 1 learned to rotate a cube in a specific way with the end goal of
      efficiently revealing object-identifying information. In Experiments 2 and 3, the
      end goal of obtaining object-identifying information was removed, but the
      stimulus-response associations were preserved. Only object views associated with
      actions learned in the context of obtaining identifying information caused
      response interference and benefits in a subsequent test phase where the object
      was irrelevant. These results demonstrate the existence of informational
      affordances: perception-action sequences acquired with the goal of information
      extraction that are automatically primed during later exposure to the object.
      Perceptual priming of actions for efficient information extraction is an
      important component of expert performance and its use of action systems to
      optimally deal with the world.

PMID- 22371199
TI  - Charcot-Marie-Tooth disease presenting as a nonhealing ulcer in a 26-year-old
      man.
AB  - A 26-year-old man presented with a nonhealing ulcer on the plantar aspect of the
      left foot of five years duration. Initial investigations were unremarkable. It
      was only after careful neurological examination that an inherited neuropathy was
      suspected. This was confirmed by nerve conduction studies and serum
      electrophoresis. He subsequently underwent partial great toe amputation for the
      ulcer and underlying first phalangeal osteomyelitis with uneventful healing.
      Neuropathic ulcers are usually associated with several well-known disorders
      including diabetes mellitus, tabes dorsalis, pernicious anemia, and sickle cell
      disease. A rarer cause is Charcot-Marie-Tooth Disease (CMTD). The report gives a
      review of CMTD and emphasizes that when faced with a nonhealing ulcer in the
      younger age group, such an underlying hereditary neuropathic cause must be
      considered.

PMID- 22371200
TI  - Isolation of quaternary benzo[c]phenanthridine alkaloids from Macleaya microcarpa
      (MAXIM.) FEDDE: comparison of maceration, Soxhlet extraction and pressurised
      liquid extraction.
AB  - INTRODUCTION: Macleaya microcarpa (Papaveraceae family) has been of considerable
      interest in recent years as a prospective source of quaternary
      benzo[c]phenanthridine alkaloids (QBAs) related to many pharmaceutical beneficial
      effects. For this purpose, a quantitative, efficient and fast method to isolate
      the QBAs from the plant material is required. OBJECTIVE: To optimise and compare
      pressurised liquid extraction (PLE) with Soxhlet extraction and maceration in
      order to estimate extraction conditions for fast and efficient isolation of QBAs
      contained in the roots of Macleaya microcarpa. METHODOLOGY: The QBAs were
      extracted by PLE, Soxhlet extraction and maceration at different conditions
      (solvent, time, etc.). Reversed phase HPLC with diode-array detector was utilised
      for their determination and quantification. To optimise the PLE procedure, the
      variable parameters, including temperature (40-150  degrees C), sample-to-inert
      material ratio, extraction time (5-30 min) and number of extraction cycles (1-4),
      were also tested. RESULTS: Quantitative determination of QBAs resulted in 0.2-2.8
      mg/g, 0.3-2.5 mg/g and 0.3-3.1 mg/g for PLE, Soxhlet extraction and maceration.
      To produce the yields mentioned above, PLE required only up to 30 min compared
      with 21 h for Soxhlet extraction and 49 days for maceration. CONCLUSION: PLE
      provided an effective and fast extraction of QBAs from M. microcarpa roots and
      can be recommended as an alternative isolation method to conventional techniques
      for QBAs from the plant sources.

PMID- 22371203
TI  - The role of appearance and motion in action prediction.
AB  - We used a novel stimulus set of human and robot actions to explore the role of
      humanlike appearance and motion in action prediction. Participants viewed videos
      of familiar actions performed by three agents: human, android and robot, the
      former two sharing human appearance, the latter two nonhuman motion. In each
      trial, the video was occluded for 400 ms. Participants were asked to determine
      whether the action continued coherently (in-time) after occlusion. The timing at
      which the action continued was early, late, or in-time (100, 700 or 400 ms after
      the start of occlusion). Task performance interacted with the observed agent. For
      early continuations, accuracy was highest for human, lowest for robot actions.
      For late continuations, the pattern was reversed. Both android and human
      conditions differed significantly from the robot condition. Given the robot and
      android conditions had the same kinematics, the visual form of the actor appears
      to affect action prediction. We suggest that the selection of the internal
      sensorimotor model used for action prediction is influenced by the observed
      agent's appearance.

PMID- 22371204
TI  - Protein S: an anticoagulant in its own right.

PMID- 22371205
TI  - A non-metal catalysed oxidation of primary azides to nitriles at ambient
      temperature.
AB  - A novel non-metal catalyzed oxidation of organic azides to nitriles under solvent
      free conditions is presented employing catalytic amounts of KI, and DABCO in aq.
      TBHP at room temperature. This non-metal catalyzed oxidation of azides provides
      good selectivity as double and triple bonds were not oxidized under the present
      reaction conditions.

PMID- 22371206
TI  - The accuracy of autotitrating CPAP-determined residual apnea-hypopnea index.
AB  - PURPOSE: Autotitrating continuous positive airway pressure (auto-CPAP) devices
      not only titrate CPAP pressures but also measure residual respiratory events. The
      aim of the present study was to determine the accuracy of auto-CPAP-derived
      residual apnea-hypopnea index (AHI). METHODS: We studied 137 consecutive patients
      (72.3% men) with obstructive sleep apnea from January 2008 to December 2010 who
      underwent in-laboratory overnight polysomnography (PSG) using auto-CPAP. We
      excluded patients with comorbidities like congestive heart disease, chronic
      obstructive pulmonary disease, or hypoventilation syndromes and patients with
      central sleep apnea. Residual AHI obtained from the auto-CPAP device by smart
      card (CPAP-AHI) was compared simultaneously with AHI from an overnight PSG on
      auto-CPAP (PSG-AHI) using Bland-Altman analysis and Wilcoxon signed-rank test.
      RESULTS: The mean AHI on the diagnostic study was 45.08 +/- 1.8. During the
      titration, auto-CPAP markedly suppressed the respiratory events (PSG-AHI, 3.40 +/
      0.20). On the other hand, CPAP-AHI was 3.35 +/- 0.17. Bland-Altman analysis
      showed good agreement between auto-CPAP-AHI and PSG-AHI (AHI mean difference of
      0.05, and the limits of agreement for the AHI were from +4.9 to -4.8). Two
      methods have also been compared with paired samples t test and no statistically
      significant difference was found (p > 0.05). CONCLUSION: Auto-CPAP can identify
      residual respiratory events equivalent to the use of PSG in a selected
      population.

PMID- 22371207
TI  - Pose prediction and virtual screening performance of GOLD scoring functions in a
      standardized test.
AB  - The performance of all four GOLD scoring functions has been evaluated for pose
      prediction and virtual screening under the standardized conditions of the
      comparative docking and scoring experiment reported in this Edition. Excellent
      pose prediction and good virtual screening performance was demonstrated using
      unmodified protein models and default parameter settings. The best performing
      scoring function for both pose prediction and virtual screening was demonstrated
      to be the recently introduced scoring function ChemPLP. We conclude that existing
      docking programs already perform close to optimally in the cognate pose
      prediction experiments currently carried out and that more stringent pose
      prediction tests should be used in the future. These should employ cross-docking
      sets. Evaluation of virtual screening performance remains problematic and much
      remains to be done to improve the usefulness of publically available active and
      decoy sets for virtual screening. Finally we suggest that, for certain
      target/scoring function combinations, good enrichment may sometimes be a
      consequence of 2D property recognition rather than a modelling of the correct 3D
      interactions.

PMID- 22371208
TI  - A review of the ticks (Acari: Ixodida) of Turkey: species diversity, hosts and
      geographical distribution.
AB  - Ticks are important ectoparasites, causing a variety of serious infectious
      diseases in humans and domestic animals. There is very limited taxonomic
      information about the tick species of Turkey in the literature, even though
      Turkey has very suitable climate and vegetation for ticks. In the current study,
      species diversity, hosts and geographical distribution of the ticks present in
      Turkey are reviewed based on taxonomic data in the literature from 1915 to 2011
      and our recent observations. The names of tick species are arranged according to
      the most recent check lists. The taxonomic records in the literature and our
      studies on actual tick samples indicated that the tick fauna of Turkey consists
      of 46 species; 38 species from Ixodidae and 8 species from Argasidae.

PMID- 22371210
TI  - Prenatal health, educational attainment, and intergenerational inequality: the
      Northern Finland Birth Cohort 1966 Study.
AB  - In this article, we study the effects of prenatal health on educational
      attainment and on the reproduction of family background inequalities in
      education. Using Finnish birth cohort data, we analyze several maternal and fetal
      health variables, many of which have not been featured in the literature on long
      term socioeconomic effects of health despite the effects of these variables on
      birth and short-term health outcomes. We find strong negative effects of mother's
      prenatal smoking on educational attainment, which are stronger if the mother
      smoked heavily but are not significant if she quit during the first trimester.
      Anemia during pregnancy is also associated with lower levels of attained
      education. Other indicators of prenatal health (pre-pregnancy obesity, mother's
      antenatal depressed mood, hypertension and preeclampsia, early prenatal care
      visits, premature birth, and small size for gestational age) do not predict
      educational attainment. Our measures explain little of the educational
      inequalities by parents' class or education. However, smoking explains 12%-and
      all health variables together, 19%-of the lower educational attainment of
      children born to unmarried mothers. Our findings point to the usefulness of
      proximate health measures in addition to general ones. They also point to the
      potentially important role played by early health in intergenerational processes.

PMID- 22371211
TI  - Metabolic fingerprinting of Tussilago farfara L. using 1H-NMR spectroscopy and
      multivariate data analysis.
AB  - INTRODUCTION: The flower bud of Tussilago farfara L. is widely used for the
      treatment of coughs, bronchitis and asthmatic disorders in traditional Chinese
      medicine. In Europe, the plant has been used as herbal remedies for virtually the
      same applications, but the leaves are preferred over flowers. OBJECTIVE: To
      systematically evaluate the chemical profiles of Tusssilago farfara leaves and
      flowers along with the identification of the polar and non-polar metabolites.
      METHODOLOGY: Metabolic profiling carried out by means of 1H-NMR spectroscopy and
      multivariate data analysis was applied to crude extracts from flowers and leaves.
      Metabolites were identified directly from the crude extracts through one
      dimensional and two-dimensional NMR spectra. RESULTS: A broad range of
      metabolites were detected without any chromatographic separation. Principal
      component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA)
      of 1H-NMR data provided a clear separation between the samples. The corresponding
      loadings plot indicated that higher levels of phenylpropanoids, amino acids,
      organic acids and fatty acids, as well as lower levels of sugars, terpenoids and
      sterols were present in the leaves, as compared with flowers. For the flowers,
      more phenylpropanoids were present in fully open flowers, while more sugars and
      fatty acids were present in flower buds. CONCLUSION: NMR spectra (one- and two
      dimensional) are useful for identifying metabolites, especially for the
      overlapped signals. The NMR-based metabolomics approach has great potential for
      chemical comparison study of the metabolome of herbal drugs.

PMID- 22371212
TI  - Bilateral autologous breast reconstruction with deep inferior epigastric artery
      perforator flaps: Review of a single surgeon's early experience.
AB  - BACKGROUND: The purpose of this study is to describe the early experience of a
      single surgeon just out of training, including preoperative conditioning,
      surgical approach, and outcomes in bilateral deep inferior epigastric artery
      perforator (DIEP) flap breast reconstruction patients. METHODS: We
      retrospectively reviewed 54 consecutive patients who underwent 108 DIEP flap
      breast reconstructions performed by a single surgeon over an initial 2.5-year
      period. RESULTS: There was 100% overall flap survival. The unplanned reoperation
      rate was 7.6% (n = 4). Minor complications including nonoperative infection,
      minor wound dehiscence, and donor site seroma occurred in 26% of patients (n =
      14). Significant late complications were abdominal wall bulge (n = 1) and fat
      necrosis < 10% of volume (n = 1). Tissue expander explantation due to infection
      occurred in 25% of attempted staged patients (two of eight); this did not seem to
      compromise their oncologic treatment or final reconstruction outcome. CONCLUSION:
      This study demonstrates the efficacy of the DIEP flap for bilateral autologous
      breast reconstruction in the immediate, staged, and delayed settings.

PMID- 22371214
TI  - Liver: new biomarker identified for nonalcoholic steatohepatitis.

PMID- 22371213
TI  - Meta-analysis of randomized controlled trials comparing lightweight and
      heavyweight mesh for Lichtenstein inguinal hernia repair.
AB  - PURPOSE: Lichtenstein inguinal hernia repair is associated with a low incidence
      of recurrence; however, the use of heavyweight mesh has been linked with chronic
      pain and foreign body sensation. It is hypothesized that the use of lightweight
      mesh may reduce these problems. This study aims to use meta-analysis to compare
      lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair.
      METHODS: Information was gathered from randomized controlled trials that compared
      lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair. The
      Cochrane Library, Medline, EMBASE, trial registries, conference proceedings and
      reference lists were searched. Primary outcome measures were chronic pain,
      foreign body sensation and hernia recurrence. Secondary outcome measures were
      duration of surgery, mean visual analogue scale (VAS) pain scores, surgical-site
      infection, testicular atrophy and haematoma/seroma. The pooled Peto odds ratio
      (OR) was calculated for categorical data and weighted mean difference (WMD) for
      continuous data. RESULTS: Six trials with 1936 hernias were included. Lightweight
      mesh was associated with reduced chronic pain (OR = 0.67, 95% CI = 0.50-0.90; p <
      0.01) and foreign body sensation (OR = 0.43, 95% CI = 0.21-0.93; p < 0.05).
      Lightweight mesh was also associated with lower VAS pain scores at 3 months after
      surgery (WMD = -0.35, 95% CI = -0.39 to -0.31; p < 0.0001). There were no
      differences in hernia recurrence (OR = 1.19, 95% CI = 0.54-2.64; p = 0.66) or
      other post-operative complications between the two groups. CONCLUSIONS: The use
      of lightweight mesh in Lichtenstein inguinal hernia repair is associated with
      less chronic pain, and foreign body sensation compared with heavyweight mesh
      without any difference in recurrence.

PMID- 22371215
TI  - Pancreas: treating pain in chronic pancreatitis--is the dilemma over?

PMID- 22371216
TI  - GERD: electrical stimulation of the lower esophageal sphincter to treat GERD.

PMID- 22371218
TI  - New understanding of gluten sensitivity.
AB  - Among gluten-related disorders, gluten sensitivity is an emerging entity that is
      characterized by a wide array of manifestations. In particular, patients complain
      of IBS-like symptoms and extraintestinal manifestations that occur shortly after
      the ingestion of gluten. Symptoms improve or disappear when gluten is withdrawn
      from the diet, and recur if gluten is reintroduced. Laboratory tests are usually
      unhelpful for diagnosis, although ~50% of patients are positive for IgG
      antigliadin antibodies. The natural history of gluten sensitivity is unknown; in
      particular, it is still to be clarified whether this disorder is permanent or
      transient and whether it is linked to autoimmunity. The pathogenesis of gluten
      sensitivity is unclear; data so far demonstrate a predominant activation of
      innate immune responses. Further research is necessary to establish the main
      clinicopathological features of gluten sensitivity, thus enabling physicians to
      improve their management of the increasing number of patients who are sensitive
      to dietary gluten.

PMID- 22371219
TI  - Antiannexin V antibodies: an underestimated source of noncirrhotic portal vein
      thrombosis?

PMID- 22371217
TI  - The biliary tree--a reservoir of multipotent stem cells.
AB  - The biliary tree is composed of intrahepatic and extrahepatic bile ducts, lined
      by mature epithelial cells called cholangiocytes, and contains peribiliary glands
      deep within the duct walls. Branch points, such as the cystic duct, perihilar and
      periampullar regions, contain high numbers of these glands. Peribiliary glands
      contain multipotent stem cells, which self-replicate and can differentiate into
      hepatocytes, cholangiocytes or pancreatic islets, depending on the
      microenvironment. Similar cells-presumably committed progenitor cells-are found
      in the gallbladder (which lacks peribiliary glands). The stem and progenitor cell
      characteristics indicate a common embryological origin for the liver, biliary
      tree and pancreas, which has implications for regenerative medicine as well as
      the pathophysiology and oncogenesis of midgut organs. This Perspectives article
      describes a hypothetical model of cell lineages starting in the duodenum and
      extending to the liver and pancreas, and thought to contribute to ongoing
      organogenesis throughout life.

PMID- 22371220
TI  - Cutaneous adverse events associated with disease-modifying treatment in multiple
      sclerosis: a systematic review.
AB  - Glatiramer acetate and interferon-beta are approved first-line disease-modifying
      treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with
      cutaneous adverse events, which may influence treatment adherence and patient
      quality of life. In this systematic review, we aimed to provide an overview of
      the clinical spectrum and the incidence of skin reactions associated with DMTs. A
      systematic literature search was performed up to May 2011 in Medline, Embase, and
      Cochrane databases without applying restrictions in study design, language, or
      publishing date. Eligible for inclusion were articles describing any skin
      reaction related to DMTs in MS patients. Selection of articles and data
      extraction were performed by two authors independently. One hundred and six
      articles were included, of which 41 (39%) were randomized controlled trials or
      cohort studies reporting incidences of mainly local injection-site reactions. A
      large number of patients had experienced some form of localized injection-site
      reaction: up to 90% for those using subcutaneous formulations and up to 33% for
      those using an intramuscular formulation. Sixty-five case-reports involving 106
      MS patients described a wide spectrum of cutaneous adverse events, the most
      frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various
      immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated
      with local injection-site reactions and a wide spectrum of generalized cutaneous
      adverse events, in particular, the subcutaneous formulations. Although some of
      the skin reactions may be severe and persistent, most of them are mild and do not
      require cessation of DMT.

PMID- 22371221
TI  - Taking advantage of the non-anticoagulant effects of heparin.

PMID- 22371222
TI  - The atypical subthalamic nucleus--an anatomical variant relevant for stereotactic
      targeting.
AB  - BACKGROUND: The improvement of PD motor symptoms by DBS of the STN depends on
      exact targeting. METHODS: A combination of MRI and multitrajectory
      microrecordings was used for localization of the STN in a group of 228
      consecutive PD patients. RESULTS: In 1% of our cases, the STN was consistently
      shifted in the anterior (3.3 +/- 0.8mm) and medial (3.0 +/- 0.9 mm) direction
      within the target plane, compared to controls. Adjustment of the original target
      coordinates after intraoperative reevaluation of the MRI and confirmation by
      typical subthalamic neuronal recordings along the deviant trajectory allowed the
      implantation of clinically effective electrodes in all cases. The relative
      improvement of the motor UPDRS at 6-months follow-up in patients with an atypical
      and typical STN was comparable. CONCLUSION: An atypical position of the STN does
      not need to complicate DBS surgery, if detected by a combination of MRI-based
      targeting and electrophysiological guidance.

PMID- 22371223
TI  - Decentral gene expression analysis for ER+/Her2- breast cancer: results of a
      proficiency testing program for the EndoPredict assay.
AB  - Gene expression profiles provide important information about the biology of
      breast tumors and can be used to develop prognostic tests. However, the
      implementation of quantitative RNA-based testing in routine molecular pathology
      has not been accomplished, so far. The EndoPredict assay has recently been
      described as a quantitative RT-PCR-based multigene expression test to identify a
      subgroup of hormone-receptor-positive tumors that have an excellent prognosis
      with endocrine therapy only. To transfer this test from bench to bedside, it is
      essential to evaluate the test-performance in a multicenter setting in different
      molecular pathology laboratories. In this study, we have evaluated the
      EndoPredict (EP) assay in seven different molecular pathology laboratories in
      Germany, Austria, and Switzerland. A set of ten formalin-fixed paraffin-embedded
      tumors was tested in the different labs, and the variance and accuracy of the
      EndoPredict assays were determined using predefined reference values. Extraction
      of a sufficient amount of RNA and generation of a valid EP score was possible for
      all 70 study samples (100%). The EP scores measured by the individual
      participants showed an excellent correlation with the reference values,
      respectively, as reflected by Pearson correlation coefficients ranging from 0.987
      to 0.999. The Pearson correlation coefficient of all values compared to the
      reference value was 0.994. All laboratories determined EP scores for all samples
      differing not more than 1.0 score units from the pre-defined references. All
      samples were assigned to the correct EP risk group, resulting in a sensitivity
      and specificity of 100%, a concordance of 100%, and a kappa of 1.0. Taken
      together, the EndoPredict test could be successfully implemented in all seven
      participating laboratories and is feasible for reliable decentralized assessment
      of gene expression in luminal breast cancer.

PMID- 22371225
TI  - One-pot sequential Ti-/Cu-catalysis for tandem amidation/Ullmann-type
      cyclization: synthesis of model benzodiazepine(di)ones promoted by microwave
      irradiation.
AB  - The application of sequential Ti-/Cu-catalysis in the model one-pot synthesis of
      benzodiazepine(di)ones promoted by microwave irradiation demonstrates the
      expediency of dual catalysis in coupling-cyclization methods useful for diversity
      oriented synthesis.

PMID- 22371224
TI  - Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL)
      immunoexpression in follicular-patterned lesions of the thyroid gland.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a protein which participates
      in iron trafficking and which is involved in cancerogenesis and cancer
      progression. Since its over-expression has been documented in thyroid
      malignancies in comparison to thyroid normal gland, in the present study, we
      aimed to determine whether the evaluation of NGAL immunoexpression may be of help
      in the differential diagnosis of follicular-patterned thyroid lesions. Our
      additional aim was to test the possible interference of endogenous biotin on the
      immunohistochemical findings. Thus, all the immunohistochemical procedures,
      carried out with labeled streptavidin biotin method, were doubly performed, with
      or without the preliminary inhibition of endogenous biotin. No NGAL staining was
      found in the normal thyroid gland nor in the nodular colloid goiters or in
      Hashimoto's thyroiditis. NGAL expression appeared to be significantly more
      frequent in the malignant tumors in comparison to benign ones (P < 0.000001).
      Even more, NGAL expression appeared to be specific (specificity 93%) for
      carcinoma and represented a sensitive method (sensitivity 84%), with high
      negative (88%) and positive (94%) predictive values, as well as high diagnostic
      accuracy (88%), in the identification of follicular-patterned thyroid malignant
      tumors. The specificity, positive predictive value and diagnostic accuracy
      lowered when biotin was not preliminary inhibited, due to the presence of false
      positives among benign Hurthle cell tumors. In conclusion, the
      immunohistochemical detection of NGAL may be helpful in the differential
      diagnosis between malignant and benign follicular-patterned lesions of the
      thyroid. The use of biotin free system or the preliminary biotin inhibition is
      warranted for the detection of NGAL in thyroid samples, especially when dealing
      with Hurthle cell tumors.

PMID- 22371226
TI  - Longevity of insulin receptor substrate1 null mice is not associated with
      increased basal antioxidant protection or reduced oxidative damage.
AB  - Insulin receptor substrate-1 null (Irs1 (-/-)) mice are long lived and
      importantly they also demonstrate increased resistance to several age-related
      pathologies compared to wild type (WT) controls. Currently, the molecular
      mechanisms that underlie lifespan extension in long-lived mice are unclear
      although protection against oxidative damage may be important. Here, we
      determined both the activities of several intracellular antioxidants and levels
      of oxidative damage in brain, skeletal muscle, and liver of Irs1 (-/-) and WT
      mice at 80, 450, and 700 days of age, predicting that long-lived Irs1 (-/-) mice
      would be protected against oxidative damage. We measured activities of both
      intracellular superoxide dismutases (SOD); cytosolic (CuZnSOD) and mitochondrial
      (MnSOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT),
      and reduced glutathione (GHS). Of these, only hepatic CAT was significantly
      altered (increased) in Irs1 (-/-) mice. In addition, the levels of protein
      oxidation (protein carbonyl content) and lipid peroxidation (4-hydroxynonenal)
      were unaltered in Irs1 (-/-) mice, although the hepatic GSH/GSSG ratio,
      indicating an oxidized environment, was significantly lower in long-lived Irs1 (
      /-) mice. Overall, our results do not support the premise that lifespan extension
      in Irs1 (-/-) mice is associated with greater tissue antioxidant protection or
      reduced oxidative damage.

PMID- 22371227
TI  - XlnR-independent signaling pathway regulates both cellulase and xylanase genes in
      response to cellobiose in Aspergillus aculeatus.
AB  - The expression levels of the cellulase and xylanase genes between the host strain
      and an xlnR disruptant were compared by quantitative RT-PCR (qPCR) to identify
      the genes controlled by XlnR-independent signaling pathway. The cellulose
      induction of the FI-carboxymethyl cellulase (cmc1) and FIb-xylanase (xynIb) genes
      was controlled by XlnR; in contrast, the cellulose induction of the FIII
      avicelase (cbhI), FII-carboxymethyl cellulase (cmc2), and FIa-xylanase (xynIa)
      genes was controlled by an XlnR-independent signaling pathway. To gain deeper
      insight into the XlnR-independent signaling pathway, the expression profile of
      cbhI was analyzed as a representative target gene. Cellobiose together with 1
      deoxynojirimycin (DNJ), a glucosidase inhibitor, induced cbhI the most
      efficiently among disaccharides composed of beta-glucosidic bonds. Furthermore,
      cellobiose with DNJ induced the transcription of cmc2 and xynIa, whereas cmc1 and
      xynIb were not induced. GUS reporter fusion analyses of truncated and mutated
      cbhI promoters revealed that three regions were necessary for effective cellulose
      induced transcription, all of which contained the conserved sequence 5'
      CCGN(2)CCN(7)G(C/A)-3' within the CeRE, which has been identified as the upstream
      activating element essential for expression of eglA in A. nidulans (Endo et al.
      2008). The data therefore delineate a pathway in which A. aculeatus perceives the
      presence of cellobiose, thereby activating a signaling pathway that drives
      cellulase and hemicellulase gene expression under the control of the XlnR
      independent regulation through CeRE.

PMID- 22371228
TI  - Viewing time as a measure of bisexual sexual interest.
AB  - Studies of bisexual sexual interest have focused mostly on measures of genital
      arousal in bisexual men and have generally failed to find evidence of a bisexual
      pattern of genital arousal. Bisexual women have rarely been studied and other
      measures of sexual interest have not been used to study bisexual interest in
      either sex. In this study, we examined a non-genital measure of sexual interest,
      viewing time, among 16 bisexual men, 19 bisexual women, 15 heterosexual men, 15
      heterosexual women, 15 homosexual men, and 10 homosexual women. Sexual
      orientation was determined from a self-report questionnaire. Stimuli were
      pictures of males and females of all five Tanner stages of sexual development.
      Participants were asked to rate the sexual appeal of the individuals depicted in
      the pictures, while the time taken to provide a response was covertly measured.
      Using a signed index that compared viewing times to pictures of sexually mature
      males and females, bisexual men and bisexual women did not look longer at
      pictures of one gender, whereas the other four groups had longer viewing times
      for pictures of one gender. Using an absolute index, the three groups of women
      showed a similar (and low) degree of gender preference. All groups showed longer
      viewing times for sexually mature individuals than for sexually immature
      individuals, suggesting that the viewing time responses of bisexual men and women
      were not produced by a general tendency to look indiscriminately at all pictures.
      There were small to moderate correlations between viewing times and rated sexual
      appeal in all groups. Results suggest that viewing time can be used to detect a
      bisexual pattern of sexual interest in bisexual men and bisexual women.

PMID- 22371231
TI  - The comparison of epicardial focused ultrasound circumferential pulmonary vein
      ablation and BOX ablation--results from experimental acute atrial fibrillation.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of focused
      ultrasound circumferential pulmonary vein ablation (CPVa) and BOX ablation (BOXa)
      in an acute atrial fibrillation (AF) model. METHODS: Twenty mongrel dogs were
      divided into either CPVa or BOXa groups. CPV or BOX focused ultrasonic ablation
      was conducted in each group after successful establishment of the AF model.
      Before-and-after ablation left atrial effective refractory period (LAERP), AF
      inducibility, and induced AF lasting time were measured in both groups. RESULTS:
      The LAERP after AF model establishment was significantly shorter than that before
      establishment (102 +/- 10 vs. 140 +/- 10 ms, p < 0.01, in the CPVa group; 105 +/-
      8 vs. 139 +/- 11 ms, p < 0.01, in the BOXa group). The AF inducibility after
      ablation was significantly lower than that before ablation in the two groups (98%
      vs. 28%, p < 0.01, in the CPVa group; 97% vs.14%, p < 0.01, in the BOXa group),
      and the induced AF lasting time after ablation was significantly shorter than
      that before ablation in both groups (233 +/- 40 vs. 70 +/- 29 s, p < 0.01, in the
      CPVa group; 240 +/- 41 vs. 34 +/- 22 s, p < 0.01, in the BOXa group). On
      intergroup comparison, AF inducibility and induced AF lasting time after ablation
      were significantly lower/shorter in the BOXa group than those in the CPVa group
      (14% vs. 28%, p = 0.021; 34 +/- 22 vs. 70 +/- 29 s, p = 0.048, respectively).
      CONCLUSIONS: In the experimental AF model, the epicardial focused ultrasound BOX
      ablation may be more effective to prevent the recurrence of AF compared with the
      CPV approach.

PMID- 22371233
TI  - OPV-like poliovirus type 1 detection in patients with severe acute respiratory
      syndrome.

PMID- 22371232
TI  - Stress and glucocorticoids increase transthyretin expression in rat choroid
      plexus via mineralocorticoid and glucocorticoid receptors.
AB  - Transthyretin (TTR) is a carrier for thyroid hormones and retinol binding
      protein. Several mutated forms of TTR cause familial amyloidotic polyneuropathy,
      an inheritable lethal disease. On the other hand, wild-type TTR has a protective
      role against Alzheimer's disease. Despite its overall importance in normal animal
      physiology and in disease, few studies have focused on its regulation. An in
      silico analysis of the rat TTR gene revealed a glucocorticoid responsive element
      in the 3' region of the first intron. Thus, we hypothesised that TTR could be
      regulated by glucocorticoid hormones and investigated the regulation of TTR
      expression in response to hydrocortisone in a rat choroid plexus cell line (RCP)
      and in primary cultures of choroid plexus epithelial cells (CPEC). In addition,
      the effect of psychosocial stress on TTR expression was analysed in rat liver,
      choroid plexus (CP) and cerebrospinal fluid (CSF). In RCP and CPEC cultures
      hydrocortisone upregulated TTR expression, an effect suppressed by glucocorticoid
      receptor and mineralocorticoid receptor antagonists. Moreover, induction of
      psychosocial stress increased TTR expression in liver, CP and CSF of animals
      subjected to acute and chronic stress conditions. Overall, we conclude that
      stress upregulates TTR expression in CP.

PMID- 22371235
TI  - Synthesis, structure, and ethylene polymerization behavior of nickel complexes
      based on benzoylmethylenetri(2-alkoxylphenyl)phosphorane.
AB  - Several new nickel complexes are prepared by the treatment of the stabilized
      ylide benzoylmethylenetri(2-alkoxylphenyl)phosphorane with Ni(cod)(2) in the
      presence of PPh(3). X-Ray diffraction studies reveal that a distorted square
      planar geometry around Ni(II) is adopted. Upon treatment with Ni(cod)(2), the
      nickel complexes are sufficiently robust for ethylene polymerization. The
      existence of 2-alkoxyl-aryl substituents on phosphorus improves the catalytic
      activities. The highest activity (2.1 * 10(6) g mol(-1) h(-1)) is achieved when
      tri(2-isopropoxy-phenyl)phosphorane is employed (5e), which is one order higher
      than the corresponding SHOP catalyst. NMR analysis shows that the polyethylene
      mainly contains terminal double bonds and is highly linear.

PMID- 22371234
TI  - Impact of a multidimensional infection control strategy on central line
      associated bloodstream infection rates in pediatric intensive care units of five
      developing countries: findings of the International Nosocomial Infection Control
      Consortium (INICC).
AB  - PURPOSE: To analyze the impact of the International Nosocomial Infection Control
      Consortium (INICC) multidimensional infection control strategy including a
      practice bundle to reduce the rates of central line-associated bloodstream
      infection (CLAB) in patients hospitalized in pediatric intensive care units
      (PICUs) of hospitals, which are members of the INICC, from nine cities of five
      developing countries: Colombia, India, Mexico, Philippines, and Turkey. METHODS:
      CLAB rates were determined by means of a prospective surveillance study conducted
      on 1,986 patients hospitalized in nine PICUs, over a period of 12,774 bed-days.
      The study was divided into two phases. During Phase 1 (baseline period), active
      surveillance was performed without the implementation of the multi-faceted
      approach. CLAB rates obtained in Phase 1 were compared with CLAB rates obtained
      in Phase 2 (intervention period), after implementation of the INICC
      multidimensional infection control program. RESULTS: During Phase 1, 1,029
      central line (CL) days were recorded, and during Phase 2, after implementing the
      CL care bundle and interventions, we recorded 3,861 CL days. The CLAB rate was
      10.7 per 1,000 CL days in Phase 1, and in Phase 2, the CLAB rate decreased to 5.2
      per 1,000 CL days (relative risk [RR] 0.48, 95% confidence interval [CI] 0.29
      0.94, P = 0.02), showing a reduction of 52% in the CLAB rate. CONCLUSIONS: This
      study shows that the implementation of a multidimensional infection control
      strategy was associated with a significant reduction in the CLAB rates in the
      PICUs of developing countries.

PMID- 22371236
TI  - Fetal hypothalamic hamartoma with suprasellar arachnoid cyst.

PMID- 22371237
TI  - Biology and function of the aryl hydrocarbon receptor: report of an international
      and interdisciplinary conference.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      present in many cells. The AhR links environmental chemical stimuli with adaptive
      responses, such as detoxification, cellular homoeostasis or immune responses.
      Furthermore, novel roles of AhR in physiological and genetic functions are being
      discovered. This is a report of a recent meeting in Dusseldorf. The meeting
      highlighted that AhR research has moved from its focus on toxic effects of
      dioxins and other environmental pollutants to its biological roles. For instance,
      it was recently discovered that AhR-responsive elements in retrotransposons
      contribute to the functional structure of the genome. Other exciting new reports
      concerned the way plant-derived compounds in our diet are necessary for a fully
      functioning immune system of the gut. Also, human brain tumours use the AhR
      system to gain growth advantages. Other aspects covered were neurotoxicology, the
      circadian rhythm, or the breadth of the adaptive and innate immune system
      (hematopoietic stem cells, dendritic cells, T cells, mast cells). Finally, the
      meeting dealt with the discovery of new xenobiotic and natural ligands and their
      use in translational medicine, or cancer biology and AhR.

PMID- 22371238
TI  - Influence of a fat-rich diet, folic acid supplementation and a human-relevant
      concentration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on the induction
      of preneoplastic lesions in the rat colon.
AB  - In the present study, the effect of three controversially discussed risk factors
      for colorectal cancer, a fat-rich diet (16% raw fat content), dietary folic acid
      supplementation (50 mg folic acid/kg lab chow) and a human-relevant concentration
      (0.1 ppm) of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP), either alone or in combination, on the induction of aberrant
      crypt foci (ACF) in the colon of male Fischer 344 rats was analyzed. The mean
      number of ACF per rat in the case of the four groups fed a fat-rich diet tended
      to be higher than that of the four groups being fed a standard diet. However, the
      increase in the mean number of ACF per rat only reached statistical significance
      in the case of the rats receiving a fat-rich lab chow supplemented with 50 mg/kg
      folic acid. Moreover, a concentration of 0.1 ppm PhIP per se, either in the
      standard or in the fat-rich lab chow, did not lead to an increase in the mean
      number of ACF per rat. In conclusion, the present study provides additional
      evidence for a colon cancer promoting effect of folic acid supplementation when
      rodents are fed the compound in supraphysiological concentrations.

PMID- 22371239
TI  - Botulinum toxin injection for hypertonicity of the upper extremity within 12
      weeks after stroke: a randomized controlled trial.
AB  - BACKGROUND: Botulinum neurotoxin type A (BoNT-A) reduces upper-extremity
      poststroke spasticity when given 6 or more months after stroke. Effects on
      functional use of the arm and hand are less apparent. OBJECTIVE: To determine the
      effect and safety of very early use of BoNT-A for patients with upper-limb
      spasticity. METHODS: The Asia Botulinum Toxin-A Clinical Trial DESIGN: ed for
      Early Post-stroke Spasticity (ABCDE-S; NCT00234546) was a multicenter,
      randomized, placebo-controlled trial conducted in patients recruited within 2 -12
      weeks of first-ever stroke. Participants with a Modified Ashworth Scale (MAS)
      score of 1+ or above received BoNT-A (Dysport) 500 U or placebo to one or more
      wrist and elbow mover muscles, plus unstructured rehabilitation. The primary
      outcome was the MAS score in the most affected joint 4 weeks after first
      injection. Follow-up was 24 weeks. RESULTS: A total of 163 patients were enrolled
      and assigned to placebo (n = 83) or BoNT-A (n = 80). Mean time since stroke was
      about 7 weeks. At 4 weeks postinjection, BoNT-A significantly improved MAS
      scores. Treatment effect-size estimates increased with higher baseline MAS scores
      from 0.45 (Q1) to 0.70 (Q3). MAS scores for all secondary end points improved
      with BoNT-A versus placebo at all time points (P < .0001, all visits). The
      Functional Motor Assessment Scale did not reveal clinically significant
      differences. No group differences in adverse events were found. Interpretation.
      BoNT-A 500 U can provide a sustained reduction in poststroke upper-limb
      spasticity when combined with rehabilitation in Asian patients who have mild-to
      moderate hypertonicity and voluntary movement, within 2 -12 weeks of stroke.
      Functional use of the arm and hand was not affected.

PMID- 22371242
TI  - Acute kidney injury: AKI in kidney transplant recipients--here to stay.

PMID- 22371243
TI  - Dialysis: Does reducing dialysate sodium level lower blood pressure?

PMID- 22371244
TI  - Transplantation: Does anemia correction delay kidney allograft dysfunction?

PMID- 22371249
TI  - Basic research: an oral cyclic peptide drug to reverse kidney fibrosis?

PMID- 22371245
TI  - The long-term renal and cardiovascular consequences of prematurity.
AB  - Infants born prematurely at <37 weeks' gestation account for over 80% of infants
      weighing <2,500 g at birth-low birth weight (LBW) infants. This designation
      remains the surrogate marker for developmental origins of adult disease. Landmark
      studies spanning four decades have shown that individuals born with a LBW are
      more likely to develop cardiovascular and renal disease in later life, which is
      believed to be related to 'developmental programming' of such adult disease
      during vulnerable periods of growth in utero and in the early postnatal period.
      There has long been ambiguity regarding the distinction between infants with
      intrauterine growth restriction and preterm infants since both show a low nephron
      endowment that is associated with subsequent hypertension and chronic kidney
      disease. Knowledge is growing specific to the preterm infant and the
      developmental associations of being born preterm with the interruption of normal
      organogenesis relative to the vascular tree and kidney. Both systems develop by
      branching morphogenesis and interruptions lead to considerable deficits in their
      structure and function. These developmental aberrations can lead to endothelial
      dysfunction, hypertension, proteinuria and metabolic abnormalities that persist
      throughout life. This Review will examine the effect of preterm birth on the
      development of cardiovascular and kidney disease in later life and will also
      discuss potential early interventions to alter the progression of disease.

PMID- 22371247
TI  - Pathogenesis of membranous nephropathy: recent advances and future challenges.
AB  - Over the past few years, considerable advances have been made in our
      understanding of the molecular pathomechanisms of human membranous nephropathy,
      inspired by studies of Heymann nephritis, a faithful experimental model of this
      disease. This research led to the identification of neutral endopeptidase, the M
      type receptor for secretory phospholipase A(2) (PLA(2)R1) and cationic bovine
      serum albumin as target antigens of circulating and deposited antibodies in
      alloimmune neonatal, adult 'idiopathic' and early-childhood membranous
      nephropathy, respectively. A genome-wide association study has provided further
      evidence for a highly significant association between PLA2R1 and HLA-DQA1 loci
      and idiopathic membranous nephropathy in patients of white ancestry. Additional
      antibody specificities for cytoplasmic antigens have also been identified, but
      their pathogenic role is uncertain. The time has come to revisit the spectrum of
      membranous nephropathies based on the newly identified antigen-antibody systems
      that should be considered as molecular signatures of the disease and that
      challenge the uniform histological definition. These signatures will soon have a
      major impact on patient care.

PMID- 22371251
TI  - Commercial antibody-based tests for diagnosis of acute Chikungunya infection.

PMID- 22371250
TI  - Timing of dialysis initiation in transplant-naive and failed transplant patients.
AB  - Over the past two decades, most guidelines have advocated early initiation of
      dialysis on the basis of studies showing improved survival in patients starting
      dialysis early. These recommendations led to an increase in the proportion of
      patients initiating dialysis with an estimated glomerular filtration rate (eGFR)
      >10 ml/min/1.73 m(2), from 20% in 1996 to 52% in 2008. During this period, the
      percentage of patients starting dialysis with an eGFR >=15 ml/min/1.73 m(2)
      increased from 4% to 17%. However, recent studies have failed to substantiate a
      benefit of early dialysis initiation and some data have suggested worse outcomes
      for patients starting dialysis with a higher eGFR. Several reasons for this
      seemingly paradoxical observation have been suggested, including the fact that
      patients requiring early dialysis are likely to have more severe symptoms and
      comorbidities, leading to confounding by indication, as well as biological
      mechanisms that causally relate early dialysis therapy to adverse outcomes.
      Patients with a failing renal allograft who reinitiate dialysis encounter similar
      problems. However, unique factors associated with a failed allograft means that
      the optimal timing of dialysis initiation in failed transplant patients might
      differ from that in transplant-naive patients with chronic kidney disease. In
      this Review, we discuss studies of dialysis initiation and compare risks and
      benefits of early versus late initiation and reinitiation of dialysis therapy.

PMID- 22371252
TI  - Poliovirus neutralization test with poliovirus pseudovirus to measure
      neutralizing antibody in humans.

PMID- 22371254
TI  - Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy
      with minicores.
AB  - We ascertained a nuclear family in which three of four siblings were affected
      with an unclassified autosomal recessive myopathy characterized by severe
      weakness, respiratory impairment, scoliosis, joint contractures, and an unusual
      combination of dystrophic and myopathic features on muscle biopsy. Whole genome
      sequence from one affected subject was filtered using linkage data and variant
      databases. A single gene, MEGF10, contained nonsynonymous mutations that co
      segregated with the phenotype. Affected subjects were compound heterozygous for
      missense mutations c.976T > C (p.C326R) and c.2320T > C (p.C774R). Screening the
      MEGF10 open reading frame in 190 patients with genetically unexplained myopathies
      revealed a heterozygous mutation, c.211C > T (p.R71W), in one additional subject
      with a similar clinical and histological presentation as the discovery family.
      All three mutations were absent from at least 645 genotyped unaffected control
      subjects. MEGF10 contains 17 atypical epidermal growth factor-like domains, each
      of which contains eight cysteine residues that likely form disulfide bonds. Both
      the p.C326R and p.C774R mutations alter one of these residues, which are
      completely conserved in vertebrates. Previous work showed that murine Megf10 is
      required for preserving the undifferentiated, proliferative potential of
      satellite cells, myogenic precursors that regenerate skeletal muscle in response
      to injury or disease. Here, knockdown of megf10 in zebrafish by four different
      morpholinos resulted in abnormal phenotypes including unhatched eggs, curved
      tails, impaired motility, and disorganized muscle tissue, corroborating the
      pathogenicity of the human mutations. Our data establish the importance of MEGF10
      in human skeletal muscle and suggest satellite cell dysfunction as a novel
      myopathic mechanism.

PMID- 22371255
TI  - Genome-wide survey and characterization of the WRKY gene family in Populus
      trichocarpa.
AB  - WRKY transcription factors participate in diverse physiological and developmental
      processes in plants. They have highly conserved WRKYGQK amino acid sequences in
      their N-termini, followed by the novel zinc-finger-like motifs, Cys2His2 or
      Cys2HisCys. To date, numerous WRKY genes have been identified and characterized
      in a number of herbaceous species. Survey and characterization of WRKY genes in a
      ligneous species would facilitate a better understanding of the evolutionary
      processes and functions of this gene family. In this study, 104 poplar WRKY genes
      (PtWRKY) were identified in the latest poplar genome sequence. According to their
      structural features, the predicted members were divided into the previously
      defined groups I-III, as described in rice. In addition, chromosomal localization
      of the genes demonstrated that there might be WRKY gene hot spots in 2.3 Mb
      regions on chromosome 14. Furthermore, approximately 83% (86 out of 104) WRKY
      genes participated in gene duplication events, including 69% (29 out of 42) gene
      pairs which exhibited segmental duplication. Using semi-quantitative RT-PCR, the
      expression patterns of subgroup III genes were investigated under different
      stresses [cold, drought, salinity and salicylic acid (SA)]. The data revealed
      that these genes presented different expression levels in response to various
      stress conditions. Expression analysis exhibited PtWRKY76 gene induced markedly
      in 0.1 mM SA or 25% PEG-6000 treatment. The results presented here provide a
      fundamental clue for cloning specific function genes in further studies and
      applications. KEY MESSAGE: This study identified 104 poplar WRKY genes and
      demonstrated WRKY gene hot spots on chromosome 14. Furthermore, semi-quantitative
      RT-PCR showed variable stress responses in subgroup III.

PMID- 22371256
TI  - Exogenous thermospermine has an activity to induce a subset of the defense genes
      and restrict cucumber mosaic virus multiplication in Arabidopsis thaliana.
AB  - We previously proposed the defensive role of a signal pathway triggered by the
      polyamine spermine (Spm) in the reaction against avirulent viral pathogens in
      Nicotiana tabacum and Arabidopsis thaliana. In this study, we showed that
      thermospermine (T-Spm), an isomer of Spm, is also active in inducing the
      expression of the genes involved in the Spm-signal pathway at a similar dose as
      Spm. Furthermore, we found that T-Spm enhances the expression of a subset of
      pathogenesis-related genes whose expression is induced during cucumber mosaic
      virus (CMV)-triggered hypersensitive response. In consistent with the above
      observation, we further showed that exogenous T-Spm can repress CMV
      multiplication with same efficiency as Spm. KEY MESSAGE: Polyamine
      thermospermine, an isomer of spermine, is able to induce a subset of
      hypersensitive response-related defense genes and can suppress cucumber mosaic
      virus multiplication in Arabidopsis thaliana.

PMID- 22371257
TI  - N-Glycosylation engineering of tobacco plants to produce asialoerythropoietin.
AB  - Erythropoietin (EPO) is a glycoprotein hormone that displays both hematopoietic
      and tissue-protective functions by binding to two distinct receptors. Recombinant
      human EPO (rhuEPO) is widely used for the treatment of anemia, but its use for
      tissue protection is limited because of potentially harmful increases in red
      blood cell mass when higher doses of rhuEPO are used. Recent studies have shown
      that asialoerythropoietin (asialo-rhuEPO), a desialylated form of rhuEPO, lacks
      hematopoietic activity, but retains cytoprotective activity. Currently, a small
      amount of asialo-rhuEPO is produced by enzymatic desialylation of rhuEPO. The
      prohibitive cost of rhuEPO, however, is a major limitation of this method. Plants
      have the ability to synthesize complex N-glycans, but lack enzymatic activities
      to add sialic acid and beta1,4-galactose to N-glycan chains. Plants could be
      genetically engineered to produce asialo-rhuEPO by introducing human beta1,4
      galactosyltransferase. The penultimate beta1,4-linked galactose residues are
      important for in vivo biological activity. In this proof of concept study, we
      show that tobacco plants co-expressing human beta1,4-galactosyltransferase and
      EPO genes accumulated asialo-rhuEPO. Purified asialo-rhuEPO binds to an Erythrina
      cristagalli lectin column, indicating that its N-glycan chains bear terminal
      beta1,4-galactose residues and that the co-expressed GalT is functionally active.
      Asialo-rhuEPO interacted with the EPO receptor (EPOR) with similar affinity as
      rhuEPO, implying that it was properly folded. The strategy described here
      provides a straightforward way to produce asialo-rhuEPO for research and
      therapeutic purposes. KEY MESSAGE: N-glycosylation pathway in tobacco plants
      could be genetically engineered to produce a tissue-protective cytokine,
      asialoerythropoietin (a desialylated form of human hormone erythropoietin).

PMID- 22371258
TI  - Novel mutation in the epithelial sodium channel causing type I
      pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited disorder with a devastating prognosis.
      Determination of chloride concentration in sweat has been the gold standard test
      for diagnosing CF for over 50 years and still remains the primary screening test.
      However, now that the genetic cause is known and can be studied, genetic
      confirmation is mandatory in every suspected patient. We present a patient who
      had been clinically diagnosed and whose genetic testing could not confirm CF,
      leading us to search for other options that may also give a positive sweat test.
      The patient turned out to suffer type 1 pseudohypoaldosteronism, a condition that
      may cause severe dehydration, hyponatremia and hyperkalemia episodes if not
      diagnosed and treated early with sodium supplementation. We found a genetic
      variation in the epithelial sodium channel gene which has not been reported
      previously, and we discuss the possibility of it being the cause of our patient's
      phenotype. CONCLUSION: this patient clearly illustrates the usefulness of genetic
      confirmation for CF for the diagnosis and genetic counselling, even when it is
      clinically oriented, and describes a novel mutation of the amiloride-sensitive
      epithelial sodium channel possibly causing type 1 pseudohypoaldosteronism.

PMID- 22371259
TI  - Sporadic congenital nonautoimmune hyperthyroidism caused by P639S mutation in
      thyrotropin receptor gene.
AB  - Germline mutations of thyrotropin receptor (TSHR) gene determining a constitutive
      activation of the receptor were identified as a molecular cause of familial or
      sporadic congenital nonautoimmune hyperthyroidism (OMIM: 609152) (Nat Genet 7:396
      401, 1994; N Engl J Med 332:150-154, 1995; Acta Endocrinol (Copenh) 100:512-518,
      1982). We report the case of an Italian child subjected to the first clinical
      investigation at 24 months for an increased growth velocity; biochemical
      investigation showed high FT4 and FT3 serum values and undetectable thyrotropin
      in the absence of anti-thyroid antibodies; the thyroid gland was normal at
      ultrasound examination. Treatment with methimazole was started at the age of 30
      months when her growth velocity was high and the bone age was advanced. DNA was
      extracted from her parents', brother's, and the patient's blood. Exons 9 and 10
      of the TSHR gene were amplified by polymerase chain reaction and subjected to
      direct sequencing. In proband, a heterozygous substitution of cytosine to thymine
      determining a proline to serine change at position 639 (P639S) of the TSHR was
      detected while the parents and brothers of the propositus, all euthyroid, showed
      only the wild-type sequence of the TSHR gene. This mutation was previously
      described as somatic in patients affected by hyperfunctioning thyroid nodules and
      as germline in a single Chinese family affected by thyrotoxicosis and mitral
      valve prolapse. This constitutively activating mutation is able to activate both
      the cyclic AMP and the inositol phosphate metabolic pathways when expressed in a
      heterologous system. In conclusion, we describe the first case of sporadic
      congenital nonautoimmune hyperthyroidism caused by de novo germinal P639S
      mutation of TSHR.

PMID- 22371260
TI  - Ulnar nerve injuries in Guyon canal: a report of 32 cases.
AB  - PURPOSE: In this study, the surgical outcomes of 32 patients with ulnar nerve
      injuries in the Guyon canal are presented. Outcomes were analyzed in relation to
      various factors such as age, surgical timing, zone of injury, and type of nerve
      reconstruction. METHODS: Between 1990 and 2007, 32 patients with injury in Guyon
      canal were managed surgically. Twelve patients had ulnar nerve injury proximal to
      its bifurcation (zone I); 14 patients had isolated motor branch injury (zone II);
      and six patients had isolated sensory branch injury (zone III). End-to-end repair
      was achieved in 12 (38%) of 32 patients, while nerve grafting was performed in 20
      (62%) cases. The mean follow-up period was 22 months. RESULTS: Good and excellent
      motor function was restored in 25 (96%) of 26 cases with motor branch injury.
      Good and excellent sensory results were achieved in 15 (83%) of 18 cases with
      sensory branch injury. Outcomes were significantly better for those who had early
      repair (<4 weeks) when compared with those who had repair 4 weeks after injury (P
      < 0.05). There were no significant differences between outcomes after end-to-end
      repair or nerve grafting (P > 0.05) and between outcomes from repair of injuries
      in different zone (P > 0.05). CONCLUSIONS: Early diagnosis and surgical treatment
      with careful dissection of the ulnar nerve branches within the canal is very
      important. Adequate exposure is usually required to repair the nerve in the Guyon
      canal. Nerve grafting in this level could give analogous results as the end-to
      end repair.

PMID- 22371262
TI  - Production and characterization of hirudin variant-1 by SUMO fusion technology in
      E. coli.
AB  - Hirudin is the most potent non-covalent inhibitor of thrombin. Several expression
      systems have been used to produce recombinant hirudin for pharmaceutical
      purposes. However, high expression of active hirudin in Escherichia coli
      cytoplasm has not been successful owing to the fact that heterogenetic small
      peptide is easily degraded in the cell. To solve this problem, we constructed a
      recombinant form of the hirudin variant-1 (HV1) as a fusion protein with the
      small ubiquitin-related modifier gene (SUMO) by use of over-lap PCR. The fusion
      gene His(6)-SUMO-HV1 was highly expressed in E. coli BL21 (DE3) in which the SUMO
      HV1 accounts for over 30% of the soluble fraction. The fusion protein was
      purified by Ni-NTA affinity chromatography and cleaved by a SUMO-specific
      protease Ulp1 to release the HV1 with natural N-terminal. The recombinant HV1
      (rHV1) was further purified by Ni-NTA affinity chromatography and then by Q anion
      exchange chromatography. N-terminal sequencing result demonstrated the purified
      rHV1 had the same N-terminal sequence as the native hirudin. MALDI-TOF/MS
      analysis indicated that the molecular weight of the purified rHV1 protein was
      6939.161 Da, which was similar to the theoretical molecular weight of rHV1 6,944
      Da. The Chromozym TH assay result showed that the anti-thrombin activity of
      purified rHV1 was 8,800 ATU/mg and comparable to the specific activity of native
      hirudin.

PMID- 22371261
TI  - Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and
      neonatal development in humanized UGT1 mice.
AB  - In humanized UDP glucuronosyltransferase-1 (hUGT1) mice that express the entire
      UGT1 locus, the maternal hepatic UGT1A genes are dramatically induced 12-14 days
      after conception. Steroid induction of the UGT1A1 gene indicates that xenobiotic
      sensors, such as the pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR), may underlie the induction process. In contrast, neonatal hUGT1
      mice display severe hyperbilirubinemia, with limited expression of the UGT1A
      genes. This study identifies PXR as both a positive and negative regulator of the
      UGT1A1 gene. Pregnancy hormones, in particular the glucocorticoids, target PXR as
      a positive regulator of human glucuronidation. Employing reverse genetics, where
      PXR has been genetically deleted, hUGT1/Pxr(-/-) mice show limited induction of
      the liver UGT1A genes during pregnancy, whereas the exact opposite occurs in
      newborn mice. Neonatal hUGT1 mice show delayed expression of hepatic UGT1A1 and
      are severely hyperbilirubinemic. However, in hUGT1/Pxr(-/-) mice,
      hyperbilirubinemia is greatly reduced due to induction of hepatic UGT1A1. Thus,
      PXR serves to repress UGT1A1 gene expression during development. Transcriptional
      silencing of the UGT1A1 gene was relieved in neonatal hUGT1 hepatocytes through
      interruption of PXR by small interfering RNA. CONCLUSION: PXR is a key regulator
      of pregnancy induced glucuronidation capacity in addition to modulating the
      severity of neonatal jaundice.

PMID- 22371264
TI  - Editorial: a systematic end to "muddling through"?

PMID- 22371263
TI  - Gene cloning and characterization of a novel highly organic solvent tolerant
      lipase from Proteus sp. SW1 and its application for biodiesel production.
AB  - Proteus sp. SW1 was found to produce an extracellular solvent tolerant lipase.
      The gene, lipA, encoding a bacterial lipase, was cloned from total Proteus sp.
      SW1 DNA. lipA was predicted to encode a 287 amino acid protein of 31.2 kDa
      belonging to the Group I proteobacterial lipases. Purified His-tagged LipA
      exhibited optimal activity at pH 10.0 and 55 degrees C. It was highly stable in
      organic solvents retaining 112% of its activity in 100% isopropanol after 24 h,
      and exhibited more than 200% of its initial activity upon exposure to 60%
      acetone, ethanol, and hexane for 18 h. Biodiesel synthesis reactions, using a
      single step addition of 13% an acyl acceptor ethanol, showed that LipA was highly
      effective at converting palm oil into biodiesel.

PMID- 22371265
TI  - Hydrogen adsorption in the metal-organic frameworks Fe2(dobdc) and
      Fe2(O2)(dobdc).
AB  - The hydrogen storage properties of Fe(2)(dobdc) (dobdc(4-) = 2,5-dioxido-1,4
      benzenedicarboxylate) and an oxidized analog, Fe(2)(O(2))(dobdc), have been
      examined using several complementary techniques, including low-pressure gas
      adsorption, neutron powder diffraction, and inelastic neutron scattering. These
      two metal-organic frameworks, which possess one-dimensional hexagonal channels
      decorated with unsaturated iron coordination sites, exhibit high initial
      isosteric heats of adsorption of -9.7(1) and -10.0(1) kJ mol(-1), respectively.
      Neutron powder diffraction has allowed the identification of three D(2) binding
      sites within the two frameworks, with the closest contacts corresponding to Fe
      D(2) separations of 2.47(3) and 2.53(5) A, respectively. Inelastic neutron
      scattering spectra, obtained from p-H(2) (para-H(2)) and D(2)-p-H(2) mixtures
      adsorbed in Fe(2)(dobdc), reveal weak interactions between two neighboring
      adsorption sites, a finding that is in opposition to a previous report of
      possible 'pairing' between neighboring H(2) molecules.

PMID- 22371267
TI  - Animal models of excessive alcohol consumption in rodents.
AB  - Numerous animal models have been developed to study excessive alcohol consumption
      in rodents. Use of such models has played a valuable role in elucidating
      biological underpinnings and environmental factors that mediate/promote excessive
      levels of alcohol drinking. A major obstacle in this work has been the need to
      overcome the natural tendency of rodents to either avoid alcohol or consume it in
      limited amounts that typically do not produce overt signs of intoxication. A
      variety of experimental approaches that entail modifying genetic and/or
      environmental factors have been employed to address this general problem and
      demonstrate excessive levels of alcohol consumption. Five different approaches
      that characterize animal models of excessive alcohol consumption are described:
      models that involve (a) scheduled access to alcohol; (b) scheduled periods of
      alcohol deprivation; (c) scheduled intermittent access to alcohol; (d) scheduled
      induced polydipsia; and (e) dependence and withdrawal experience. Each of the
      models possesses unique experimental features that engender excessive levels of
      alcohol consumption. Both advantages and disadvantages for each model are
      described along with discussion of future challenges to be considered in
      developing more optimal models. Ultimately, the validity and usefulness of these
      models will lie in their ability to serve as a platform for studying biological
      underpinnings and environmental influences that drive increased motivation for
      alcohol seeking and consumption, as well as evaluation of treatment strategies
      that effectively reduce excessive levels of alcohol consumption.

PMID- 22371266
TI  - Tbx1 regulates oral epithelial adhesion and palatal development.
AB  - Cleft palate, the most frequent congenital craniofacial birth defect, is a
      multifactorial condition induced by the interaction of genetic and environmental
      factors. In addition to complete cleft palate, a large number of human cases
      involve soft palate cleft and submucosal cleft palate. However, the etiology of
      these forms of cleft palate has not been well understood. T-box transcriptional
      factor (Tbx) family of transcriptional factors has distinct roles in a wide range
      of embryonic differentiation or response pathways. Here, we show that genetic
      disruption of Tbx1, a major candidate gene for the human congenital disorder
      22q11.2 deletion syndrome (Velo-cardio-facial/DiGeorge syndrome), led to abnormal
      epithelial adhesion between the palate and mandible in mouse, resulting in
      various forms of cleft palate similar to human conditions. We found that
      hyperproliferative epithelium failed to undergo complete differentiation in Tbx1
      null mice (Tbx1(-/-)). Inactivation of Tbx1 specifically in the keratinocyte
      lineage (Tbx1(KCKO)) resulted in an incomplete cleft palate confined to the
      anterior region of the palate. Interestingly, Tbx1 overexpression resulted in
      decreased cell growth and promoted cell-cycle arrest in MCF7 epithelial cells.
      These findings suggest that Tbx1 regulates the balance between proliferation and
      differentiation of keratinocytes and is essential for palatal fusion and oral
      mucosal differentiation. The impaired adhesion separation of the oral epithelium
      together with compromised palatal mesenchymal growth is an underlying cause for
      various forms of cleft palate phenotypes in Tbx1(-/-) mice. Our present study
      reveals new pathogenesis of incomplete and submucous cleft palate during
      mammalian palatogenesis.

PMID- 22371268
TI  - Simultaneous acquisition of PAR and PAIN spectra.
AB  - We present a scheme that allows the simultaneous detection of PAR and PAIN
      correlation spectra in a single two-dimensional experiment. For both spectra, we
      obtain almost the same signal-to-noise ratio as if a PAR or PAIN spectrum is
      recorded separately, which in turn implies that one of the spectra may be
      considered additional information for free. The experiment is based on the
      observation that in a PAIN experiment, the PAR condition is always also
      fulfilled. The performance is demonstrated experimentally using uniformly
      (13)C,(15)N-labeled samples of N-f-MLF-OH and ubiquitin.

PMID- 22371269
TI  - Alpha2C-adrenoceptors play a prominent role in sympathetic constriction of
      porcine pulmonary arteries.
AB  - Enhanced pulmonary vasoconstriction in response to injuries of the central
      nervous system and hypoxia result in pulmonary edema due to increased sympathetic
      activation. This study aimed to characterize alpha(2)-adrenoceptor (AR)-mediated
      responses in porcine pulmonary arteries. alpha(2)-AR-mediated vasoconstriction
      was studied using a tissue bath protocol. alpha(2)-AR protein was determined by
      Western blotting. UK14304 (alpha(2)-AR agonist) elicited only a slight
      contraction in pulmonary arteries compared to veins. Verapamil (voltage-operated
      Ca(2+) channel blocker), 2-APB (store-operated Ca(2+) channel inhibitor), and
      P1075 (K(ATP) channel opener) induced a marked decrease of the basal tone in
      veins, but not in arteries. The UK14304-induced contraction in arteries was
      enhanced by (S)-(-)-Bay K 8644 (L-type Ca(2+) channel activator), N (omega)-nitro
      L: -arginine methyl ester hydrochloride (L-NAME, eNOS inhibitor), and (S)-(-)-Bay
      K 8644 plus L-NAME to the same extent. Endothelium denudation failed to affect
      the UK14304 response. (S)-(-)-Bay K 8644 did not increase the maximal
      noradrenaline (non-selective alpha-AR agonist) or phenylephrine (alpha(1)-AR
      agonist) response. The rightward shift of the concentration-response curve to
      noradrenaline by prazosin (alpha(1)-AR antagonist) plus (S)-(-)-Bay K 8644 was
      smaller and non-parallel compared to that in the presence of prazosin alone.
      UK14304 responses were inhibited by MK912 (alpha(2C)-AR antagonist). Affinity of
      MK912 (pA(2) 9.76) and Western blotting analysis argue for an involvement of
      alpha(2C)-ARs in noradrenaline-induced contraction of pulmonary arteries. It is
      concluded that postjunctional alpha(2C)-ARs predominantly mediate contraction in
      porcine pulmonary arteries when the cytosolic Ca(2+) concentration is elevated.
      alpha(2C)-AR antagonists may be beneficial in the treatment of pulmonary edema.

PMID- 22371270
TI  - Metabolites from the leaf extract of Serjania yucatanensis with trypanocidal
      activity against Trypanosoma cruzi.
AB  - The bioassay-guided phytochemical investigation of the leaf extract of Serjania
      yucatanensis, a woody climbing plant endemic to the Yucatan peninsula, led to the
      identification of a mixture of a triterpene [lup-20(29)-en-3-one] and an
      oxygenated sesquiterpene (beta-caryophyllene oxide), as that responsible for the
      originally detected trypanocidal activity in the organic crude extract. Results
      showed that the mixture of lup-20(29)-en-3-one and beta-caryophyllene oxide is
      active against trypomastigotes of Trypanosoma cruzi (IC(50) =80.3 MUg/mL) and
      inhibits the egress of trypomastigotes from infected Vero cells (when tested at
      100 MUg/mL) without being cytotoxic.

PMID- 22371271
TI  - Larvicidal activity of silver nanoparticles synthesized using Pergularia daemia
      plant latex against Aedes aegypti and Anopheles stephensi and nontarget fish
      Poecillia reticulata.
AB  - In present study, the bioactivity of latex-producing plant Pergularia daemia as
      well as synthesized silver nanoparticles (AgNPs) against the larval instars of
      Aedes aegypti and Anopheles stephensi mosquito larvae was determined. The range
      of concentrations of plant latex (1,000, 500, 250, 125, 62.25, and 31.25 ppm) and
      AgNPs (10, 5, 2.5, 1.25, 0.625, and 0.3125 ppm) were prepared. The LC(50) and
      LC(90) values for first, second, third, and fourth instars of synthesized AgNPs
      treated first, second, third, and fourth instars of A. aegypti (LC(50) = 4.39,
      5.12, 5.66, 6.18; LC(90) = 9.90, 11.13, 12.40, 12.95 ppm) and A. stephensi
      (LC(50) = 4.41, 5.35, 5.91, 6.47; LC(90) = 10.10, 12.04, 13.05, 14.08 ppm) were
      found many fold lower than crude latex-treated A. aegypti (LC(50) = 55.13, 58.81,
      75.66, 94.31; LC(90) = 113.00, 118.25, 156.95, 175.71 ppm) and A. stephensi
      (LC(50) = 81.47, 92.09, 96.07, 101.31; LC(90) = 159.51, 175.97, 180.67, 190.42
      ppm). The AgNPs did not exhibit any noticeable effects on Poecillia reticulata
      after either 24 or 48 h of exposure at their LC(50) and LC(90) values against
      fourth-instar larvae of A. aegypti and A. stephensi. The UV-visible analysis
      shows absorbance for AgNPs at 520 nm. TEM reveals spherical shape of synthesized
      AgNPs. Particle size analysis revealed that the size of particles ranges from 44
      to 255 nm with average size of 123.50 nm. AgNPs were clearly negatively charged
      (zeta potential -27.4 mV). This is the first report on mosquito larvicidal
      activity P. daemia-synthesized AgNPs.

PMID- 22371272
TI  - Quantitative trait loci for sensitivity to ethanol intoxication in a
      C57BL/6J*129S1/SvImJ inbred mouse cross.
AB  - Individual variation in sensitivity to acute ethanol (EtOH) challenge is
      associated with alcohol drinking and is a predictor of alcohol abuse. Previous
      studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse
      strains differ in responses on certain measures of acute EtOH intoxication. To
      gain insight into genetic factors contributing to these differences, we performed
      quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia
      (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration
      in a B6*S1 F2 population. We confirmed that S1 showed greater EtOH-induced
      hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL
      analysis revealed several additive and interacting loci for various phenotypes,
      as well as examples of genotype interactions with sex. QTLs for different EtOH
      phenotypes were largely non-overlapping, suggesting separable genetic influences
      on these behaviors. The most compelling main-effect QTLs were for hypothermia on
      chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with
      loci repeatedly linked to EtOH drinking in previous mouse studies. The
      architecture of the traits we examined was complex but clearly amenable to
      dissection in future studies. Using integrative genomics strategies, plausible
      functional and positional candidates may be found. Uncovering candidate genes
      associated with variation in these phenotypes in this population could ultimately
      shed light on genetic factors underlying sensitivity to EtOH intoxication and
      risk for alcoholism in humans.

PMID- 22371273
TI  - 15-deoxy-Delta12,14 -prostaglandin J2 reduces recruitment of bone marrow-derived
      monocyte/macrophages in chronic liver injury in mice.
AB  - 15-Deoxy-Delta(12,14) -Prostaglandin J(2) (15d-PGJ(2) ), a natural peroxisome
      proliferator-activated receptor gamma (PPAR-gamma) ligand, has been implicated as
      a new antiinflammatory compound with possible clinical applications. Based on
      this concept, this study was designed to evaluate the effects of 15d-PGJ(2) on
      bone marrow-derived monocyte/macrophage (BMM) migration, phagocytosis, and
      cytokine expression after liver injury using mouse models induced by cholestasis
      or carbon tetrachloride. Mice were lethally irradiated and received bone marrow
      transplants from enhanced green fluorescent protein transgenic mice. Our results
      showed that recruitment of BMM was significantly increased during chronic liver
      injury, and that 15d-PGJ(2) administration reduced BMM, but not neutrophil,
      dendritic, or T cell migration toward the damaged liver, involving reactive
      oxygen species generation and independently of PPAR-gamma. Moreover, 15d-PGJ(2)
      inhibited the phagocytic activity of BMM and down-regulated inflammatory cytokine
      expression in vivo and in vitro. Accordingly, hepatic inflammation and fibrosis
      were strikingly ameliorated after 15d-PGJ(2) administration. CONCLUSION: Our
      findings strongly suggest the antiinflammation and antifibrogenic potential of
      15d-PGJ(2) in chronic liver diseases.

PMID- 22371274
TI  - Neurovascular unit: a focus on pericytes.
AB  - The blood-brain barrier (BBB) is a highly specialized system that controls the
      exchanges between the blood and the central nervous system (CNS). This barrier
      shields the CNS from toxic substances in the blood and provides nutrients to CNS,
      thus playing an essential role in the maintenance of homeostasis. The anatomical
      basis of the BBB is formed by the endothelial cells of brain microvasculature,
      with elaborated tight and adherens junctions, which together with pericytes, the
      basement membrane, and astrocytes, as well as neurons, microglia and
      oligodendrocytes form the neurovascular unit. The interaction between all these
      components guarantees a proper environment for neural function and a restricted
      permeability and transport. Pericytes were initially reported by Rouget in 1873
      and since then they have been recognized as an important component of the BBB,
      despite the difficulty of their identification. Diverse functions have been
      assigned to pericytes, including a role in BBB properties, hemostasis, and
      angiogenesis, as well as a contractile, immune, and phagocytic function. These
      cells are also seen like multipotent cells and so with a great potential for
      therapy. Here, we review the neurovascular unit composition and the interplay
      between the diverse components, addressing pericytes with a particular detail.

PMID- 22371277
TI  - Multiple sclerosis: Which MRI findings predict MS development in children?

PMID- 22371276
TI  - Urban inequities; urban rights: a conceptual analysis and review of impacts on
      children, and policies to address them.
AB  - This paper explores current conceptual understanding of urban social,
      environmental, and health inequality and inequity, and looks at the impact of
      these processes on urban children and young people in the 21st century. This
      conceptual analysis was commissioned for a discussion paper for UNICEF's flagship
      publication: State of the World's Children 2012: Children in an Urban World. The
      aim of the paper is to examine evidence on the meaning of urban inequality and
      inequity for urban children and young people. It further looks at the
      controversial policies of targeting "vulnerable" young people, and policies to
      achieve the urban MDGs. Finally, the paper looks briefly at the potential of
      concepts such as environment justice and rights to change our understanding of
      urban inequality and inequity.

PMID- 22371275
TI  - Neuropsychopharmacology and neurogenetic aspects of executive functioning: should
      reward gene polymorphisms constitute a diagnostic tool to identify individuals at
      risk for impaired judgment?
AB  - Executive functions are processes that act in harmony to control behaviors
      necessary for maintaining focus and achieving outcomes. Executive dysfunction in
      neuropsychiatric disorders is attributed to structural or functional pathology of
      brain networks involving prefrontal cortex (PFC) and its connections with other
      brain regions. The PFC receives innervations from different neurons associated
      with a number of neurotransmitters, especially dopamine (DA). Here we review
      findings on the contribution of PFC DA to higher-order cognitive and emotional
      behaviors. We suggest that examination of multifactorial interactions of an
      individual's genetic history, along with environmental risk factors, can assist
      in the characterization of executive functioning for that individual. Based upon
      the results of genetic studies, we also propose genetic mapping as a probable
      diagnostic tool serving as a therapeutic adjunct for augmenting executive
      functioning capabilities. We conclude that preservation of the neurological
      underpinnings of executive functions requires the integrity of complex neural
      systems including the influence of specific genes and associated polymorphisms to
      provide adequate neurotransmission.

PMID- 22371278
TI  - Stroke. Plaque inflammation predicts risk of recurrent stroke.

PMID- 22371283
TI  - Neurodegenerative disease. Mesenchymal stem cells conditioned to secrete
      neurotrophic factors provide hope for Huntington disease.

PMID- 22371279
TI  - Hypothermia for acute brain injury--mechanisms and practical aspects.
AB  - Hypothermia is widely accepted as the gold-standard method by which the body can
      protect the brain. Therapeutic cooling--or targeted temperature management (TTM)-
      is increasingly being used to prevent secondary brain injury in patients admitted
      to the emergency department and intensive care unit. Rapid cooling to 33  degrees
      C for 24 h is considered the standard of care for minimizing neurological injury
      after cardiac arrest, mild-to-moderate hypothermia (33-35  degrees C) can be used
      as an effective component of multimodal therapy for patients with elevated
      intracranial pressure, and advanced cooling technology can control fever in
      patients who have experienced trauma, haemorrhagic stroke, or other forms of
      severe brain injury. However, the practical application of therapeutic
      hypothermia is not trivial, and the treatment carries risks. Development of
      clinical management protocols that focus on detection and control of shivering
      and minimize the risk of other potential complications of TTM will be essential
      to maximize the benefits of this emerging therapeutic modality. This Review
      provides an overview of the potential neuroprotective mechanisms of hypothermia,
      practical considerations for the application of TTM, and disease-specific
      evidence for the use of this therapy in patients with acute brain injuries.

PMID- 22371285
TI  - Cerebrovascular disease: CR1 variant increases risk of cerebral amyloid
      angiopathy.

PMID- 22371287
TI  - Egg morphology of nine species of Pollenia Robineau-Desvoidy, 1830 (Diptera:
      Calliphoridae).
AB  - Egg morphology of nine species of the cluster fly genus Pollenia Robineau
      Desvoidy was studied with scanning electron microscopy. Funnel-shaped micropylar
      area, chorion covered with centrally depressed hexagons, well developed hatching
      pleats on the dorsal surface encompassing the median area were found in eggs of
      all species: P. amentaria (Scopoli), P. angustigena Wainwright, P. atramentaria
      (Meigen), P. labialis Robineau-Desvoidy, P. mayeri Jacentkovsky, P. pediculata
      Macquart, P. rudis (Fabricius), P. similis (Jacentkovsky), and P. vagabunda
      (Meigen). Untypical for Calliphoridae, a dual morphological structure of plastron
      bearing area is described here for the first time. On the basis of our
      observations, all species studied share the presence of a plastron respiratory
      function on the entire surface between the hatching lines. Differences between
      species were found in the shape of the longitudinal hatching pleats and the
      proportion between 'island pattern' and 'hexagonal pattern' of their chorionic
      surface, and in the intensity of perforation of hexagons of the median area.
      Comparisons of Pollenia egg morphology with that of other representatives of
      Calliphoridae revealed its unique structure, allowing easy differentiation from
      other representatives of the family.

PMID- 22371286
TI  - Hypertension and risk of uterine leiomyomata in US black women.
AB  - BACKGROUND: Previous studies have found a positive association between
      hypertension and risk of hysterectomy-confirmed uterine leiomyomata (UL). The
      association of hypertension with UL confirmed by ultrasound or other surgery is
      less clear. METHODS: The present study evaluated the association of hypertension
      with UL incidence according to confirmation method (hysterectomy, other surgery
      or ultrasound) in the Black Women's Health Study, 1997-2007. We collected
      prospective data every 2 years on physician-diagnosed hypertension and UL in 22
      530 premenopausal women. Validation sub-studies confirmed 99 and 96% of
      hypertension and UL self-reported diagnoses, respectively. Cox regression was
      used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs)
      for the association of hypertension and UL, adjusting for potential confounders.
      RESULTS: During 172 162 person-years of follow-up, there were 6447 incident cases
      of UL confirmed by ultrasound (n = 5111), hysterectomy (n = 670) or other surgery
      (n = 666). Treated hypertension was associated with UL confirmed by hysterectomy
      (IRR = 1.32, 95% CI: 1.06, 1.63), but it was not associated with UL confirmed by
      ultrasound (IRR = 1.05, 95% CI: 0.96, 1.16) or other surgery (IRR = 1.13, 95% CI:
      0.88, 1.46). CONCLUSIONS: Treated hypertension was associated with UL confirmed
      by hysterectomy, but not UL confirmed by other methods (other surgery or
      ultrasound). These data suggest it is premature to conclude that hypertension is
      related to an increased risk of UL. Additional studies are needed to assess
      whether the association with hysterectomy-confirmed UL can be explained by other
      sources of bias, such as patient or physician preferences for specific types of
      medical care.

PMID- 22371288
TI  - Epigenetic regulation of human cis-natural antisense transcripts.
AB  - Mammalian genomes encode numerous cis-natural antisense transcripts (cis-NATs).
      The extent to which these cis-NATs are actively regulated and ultimately
      functionally relevant, as opposed to transcriptional noise, remains a matter of
      debate. To address this issue, we analyzed the chromatin environment and RNA Pol
      II binding properties of human cis-NAT promoters genome-wide. Cap analysis of
      gene expression data were used to identify thousands of cis-NAT promoters, and
      profiles of nine histone modifications and RNA Pol II binding for these promoters
      in ENCODE cell types were analyzed using chromatin immunoprecipitation followed
      by sequencing (ChIP-seq) data. Active cis-NAT promoters are enriched with
      activating histone modifications and occupied by RNA Pol II, whereas weak cis-NAT
      promoters are depleted for both activating modifications and RNA Pol II. The
      enrichment levels of activating histone modifications and RNA Pol II binding show
      peaks centered around cis-NAT transcriptional start sites, and the levels of
      activating histone modifications at cis-NAT promoters are positively correlated
      with cis-NAT expression levels. Cis-NAT promoters also show highly tissue
      specific patterns of expression. These results suggest that human cis-NATs are
      actively transcribed by the RNA Pol II and that their expression is
      epigenetically regulated, prerequisites for a functional potential for many of
      these non-coding RNAs.

PMID- 22371289
TI  - Streptococcal infections in patients with chronic granulomatous disease: case
      report and review of the literature.
AB  - Streptococcus intermedius caused a liver abscess in a patient with chronic
      granulomatous disease (CGD). In contrast to typical staphylococcal abscesses in
      CGD, this abscess was liquid, easily drained, and resolved without surgery or
      steroids. This case and literature review provide insight into this organism's
      pathogenesis, including in CGD.

PMID- 22371290
TI  - Evaluation of the reactivity of sera from patients with systemic lupus
      erythematosus against the human MCP1.
AB  - This study evaluates metaphase chromosome protein 1 (MCP1), a nuclear antigen, as
      a diagnostic marker for systemic lupus erythematosus (SLE). Reactivity of sera
      from 114 Portuguese patients with autoimmune rheumatic disease or from healthy
      blood donors (HBD), against MCP1, produced in bacteria (bact-MCP1) or in its
      native form (native-MCP1), was determined by immunoblotting. Predictive and
      discriminative power of MCP1 reactivity for SLE diagnosis in disease-control
      groups was evaluated by logistic regression, its diagnostic value determined by
      receiver-operating characteristic analysis and compared with similar analysis of
      antinuclear antibody and double-stranded DNA (dsDNA). We demonstrated that native
      MCP1, in contrast to bact-MCP1, reacts with SLE sera with significant predictive
      and discriminative power versus other autoimmune diseases (odds ratio [OR]
      <=3.537 and >=3.265; area under the receiver-operating characteristic curve [AUC]
      <=0.643 and >=0.636) or versus HBD (OR = 5.006; AUC = 0.671), showing a good
      diagnostic power with high specificity (82.1% versus HBD) and low sensitivity for
      SLE, similar to those of dsDNA. The reactivity of SLE sera with native-MCP1 was
      shown to be dependent on the presence of phosphorylated residues. Native-MCP1 was
      shown to have diagnostic value as a specific marker for SLE diagnosis and,
      therefore, is a suitable substrate for a new antibody test. The widely reported
      importance of phosphorylated epitopes as targets for autoantibodies in SLE could
      also be confirmed for native-MCP1.

PMID- 22371291
TI  - Study of the expression of toll-like receptors in different histological types of
      colorectal polyps and their relationship with colorectal cancer.
AB  - PURPOSE: Dysregulation of toll-like receptors (TLR) signaling can result in
      chronic inflammatory and over-exuberant repair responses. The aim of this study
      was to investigate the expression and clinical relevance of TLR in colorectal
      polyps. METHODS: The expression levels of six TLR were analyzed in 70 patients
      with different histological types of colorectal polyps, 38 of which developed
      colorectal carcinoma (CC). These analyses were performed by real-time polymerase
      chain reaction, western blot, and immunohistochemistry. RESULTS: TLR9 expression
      was higher in hyperplastic or adenomatous polyps compared to other polyp types.
      Hyperplastic polyps also showed increased TLR7 levels compared to the other polyp
      types. TLR7 expression was lower in both hyperplastic and tubulovillous adenoma
      polyps from patients who developed CC. TLR9 expression was decreased in
      hyperplastic and villous polyps from patients who developed CC. CONCLUSIONS: Our
      findings suggest a possible protective role of TLR expression against malignant
      transformation in the colorectal mucosa. TLR may represent a pathological marker
      of CC risk in colorectal polyps. The role of these factors in the pathology of
      colorectal polyps deserves further investigation.

PMID- 22371292
TI  - Simultaneous monitoring of cytomegalovirus-specific antibody and T-cell levels in
      seropositive heart transplant recipients.
AB  - PURPOSE: Human cytomegalovirus (CMV) active infection (CMV infection) poses
      serious risks to CMV-seropositive heart transplant recipients. We evaluated the
      usefulness of simultaneous assessment of CMV-specific values for parameters of
      the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in
      the identification of heart recipients at risk of developing CMV infection after
      transplantation. METHODS: We prospectively studied 38 CMV-seropositive heart
      recipients. Anti-CMV antibody titers were assessed using enzyme-linked
      immunosorbent assays. CD4+ and CD8+ T-cell responses to overlapping peptide pools
      of the CMV proteins pp65 and immediate early protein-1 (IE1) were evaluated by
      flow cytometry. Immunological studies were performed before transplantation and
      at 30 days after transplantation. Patients with CMV infection were compared with
      heart recipients without CMV infection. RESULTS: During the 6-month follow-up
      period, 13 (34.2%) patients developed CMV infection. At baseline, the mean anti
      CMV-IgG antibody titer was lower in patients who developed CMV infection. This
      difference remained at 30 days after transplantation. One month after
      transplantation, the mean percentage of IE1-specific CD8+ T cells that are IFNg
      positive (CD8/IFNg + IE1) was lower in CMV-infected patients. The predictive
      value of these variables at 30 days was increased when they were combined. Cox
      regression analysis revealed an association between the risk of developing CMV
      infection and the combination marker (low anti-CMV titer [<16,100] and low
      CD8/IFNg + IE1 percentages [<0.40%], relative hazard, 6.07; p = 0.019). The
      combination marker remained significant after adjustment for clinical variables.
      CONCLUSIONS: This novel approach of a simultaneous assessment of specific anti
      CMV antibody titers and CD8/IFNg + IE1 percentages might help identify heart
      transplant recipients with an increased risk of developing CMV infection.

PMID- 22371293
TI  - The Multidrug Resistant Modulator HZ08 Reverses Multidrug Resistance via P
      glycoprotein Inhibition and Apoptosis Sensitization in Human Epidermoid Carcinoma
      Cell Line KBv200.

PMID- 22371294
TI  - Pharmacokinetic-pharmacodynamic evaluation of daptomycin, tigecycline, and
      linezolid versus vancomycin for the treatment of MRSA infections in four western
      European countries.
AB  - PURPOSE: To evaluate the usefulness of daptomycin, tigecycline, and linezolid for
      the treatment of MRSA infection compared with vancomycin in Belgium, the United
      Kingdom/Ireland, and Spain. METHODS: The methodology included the following
      steps: acquisition of microbiological and pharmacokinetic data, Monte Carlo
      simulation, estimation of the probability of target attainment (PTA), and
      calculation of the cumulative fraction of response (CFR). RESULTS: We showed that
      differences in the susceptibility of MRSA strains among countries may justify
      differences in the antibiotic dose selection. Two, 3, and 4 g daily of vancomycin
      seem be adequate in Belgium, Spain, and United Kingdom/Ireland respectively. The
      CFR obtained with 50 mg tigecycline every 12 h was higher in Spain than in
      Belgium and the United Kingdom/Ireland, but with the highest dose (100 mg q12h)
      the CFR was always 100%. At least 8 mg/kg daptomycin is necessary in United
      Kingdom/Ireland, but 4 mg/kg may be sufficient in Spain, and probably in Belgium.
      Six hundred mg q12h linezolid may be adequate in the four countries. CONCLUSION:
      Our study reinforces the idea that the local MIC distribution must be considered
      in order to increase the probability of success of empirical treatment and must
      be periodically updated.

PMID- 22371295
TI  - Identification of clinical isolates of anaerobic bacteria using matrix-assisted
      laser desorption ionization-time of flight mass spectrometry.
AB  - We evaluated the use of matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF) for the rapid identification of anaerobic
      bacteria that had been isolated from clinical specimens and previously identified
      by 16s rRNA sequencing. The Bruker Microflex MALDI-TOF instrument with the
      Biotyper Software was used. We tested 152 isolates of anaerobic bacteria from 24
      different genera and 75 different species. A total of 125 isolates (82%) had
      Biotyper software scores greater than 2.0 and the correct identification to genus
      and species was made by MALDI-TOF for 120 (79%) of isolates. Of the 12 isolates
      with a score between 1.8 and 2.0, 2 (17%) organisms were incorrectly identified
      by MALDI-TOF. Only 15 (10%) isolates had a score less than 1.8 and MALDI-TOF gave
      the wrong genus and species for four isolates, the correct genus for two
      isolates, and the correct genus and species for nine isolates. Therefore, we
      found the Bruker MALDI-TOF MicroFlex LT with an expanded database and the use of
      bacteria extracts rather than whole organisms correctly identified 130 of 152
      (86%) isolates to genus and species when the cut-off for an acceptable
      identification was a spectrum score >=1.8.

PMID- 22371296
TI  - Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations.
AB  - DNA repair genes play an important role in maintaining stability and integrity of
      genomic DNA. Polymorphisms in nucleotide excision repair genes may cause
      variations in DNA repair capacity phenotype and thus contribute to cancer risk.
      In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free
      controls, we investigated the association between three functional single
      nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A)
      in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used
      the Taqman assays to genotype these three SNPs and logistic regression models to
      estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that
      only the rs873601A variant genotypes were associated with a significant higher
      risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA
      vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG).
      Stratification analysis indicated that this risk was more pronounced in subgroups
      of older age (>59 years), males, ever-smokers, and patients with NGCA. All these
      were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We
      then performed expression analysis using gastric cancer adjacent normal tissues
      from 141 patients and found that the A variant allele was associated with non
      significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis
      using mRNA expression data from the HapMap suggested that the A allele was
      associated with significantly reduced expression of XPG mRNA in normal cell lines
      for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different
      ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG
      variants may contribute to the risk of gastric cancer. Larger studies with
      different ethnic populations are warranted to validate our findings.

PMID- 22371298
TI  - Importance of patient history and physical examination in rheumatoid arthritis
      compared to other chronic diseases: results of a physician survey.
AB  - OBJECTIVE: To survey physicians' opinions concerning the relative importance of 5
      clinical encounter components-vital signs, patient history, physical examination,
      laboratory tests, and ancillary studies-in the diagnosis and management of 8
      chronic diseases. METHODS: A SurveyMonkey internet survey was e-mailed to 7,265
      US physicians, including 3,542 rheumatologists and 3,723 nonrheumatologists, with
      the following query: "Please indicate the relative importance of 5 sources of
      information-vital signs, patient history, physical examination, laboratory tests,
      and ancillary studies-in diagnosis of congestive heart failure (CHF), diabetes
      mellitus, hypercholesterolemia, hypertension, lymphoma, pulmonary fibrosis,
      rheumatoid arthritis (RA), and ulcerative colitis." The response options were 0
      20%, 21-40%, 41-60%, 61-80%, and 81-100%. A second query with an identical
      structure addressed management of the 8 diseases. The proportions of physicians
      who estimated each component as most (or tied for most) important in diagnosis or
      in management were computed. RESULTS: The survey was completed by 313 physicians
      (154 rheumatologists and 159 nonrheumatologists). More than 90% estimated vital
      signs as most important for hypertension, and laboratory tests for diabetes
      mellitus and hypercholesterolemia. More than 70% estimated ancillary studies as
      most important for lymphoma, pulmonary fibrosis, and ulcerative colitis. Patient
      history and physical examination were estimated as most important for RA and CHF
      by >=50% of nonrheumatologists. CONCLUSION: RA and CHF were the only 2 of the 8
      diseases studied for which >=50% of nonrheumatologists estimated a patient
      history and physical examination as most important for diagnosis and management.
      Confirmation and extension of these observations in actual care may have
      implications for reimbursement and organization of clinical care.

PMID- 22371299
TI  - A role for Drosophila Wnt-4 in heart development.
AB  - In vertebrates, different Wnt-signaling pathways are required in a temporally
      coordinated manner to promote cardiogenesis. In Drosophila, wingless holds an
      essential role in heart development. Among the known Drosophila Wnts is DWnt4,
      the function of which has been studied in various developmental processes except
      for heart development. We re-evaluated the expression pattern of DWnt4 during
      embryogenesis and show that transcripts are not restricted to the dorsal ectoderm
      but are also present in the cardiogenic mesoderm. Moreover, we detect DWnt4 mRNA
      transcripts in myocardial cells by stage 16. The heart phenotype in DWnt4 mutant
      embryos is characterized by various degrees of disrupted expression of different
      cardiac markers. Overexpression of Dwnt4 also affects heart marker expression,
      which can be partially rescued by simultaneous inhibition of PKC. Our data reveal
      a role for DWnt4 in cardiogenesis; however, integration of DWnt4 with other known
      signaling pathways that function in heart development still awaits further
      investigation.

PMID- 22371300
TI  - Special issue on interpersonal psychotherapy.

PMID- 22371301
TI  - Propranolol reduces implicit negative racial bias.
AB  - BACKGROUND: Implicit negative attitudes towards other races are important in
      certain kinds of prejudicial social behaviour. Emotional mechanisms are thought
      to be involved in mediating implicit "outgroup" bias but there is little evidence
      concerning the underlying neurobiology. The aim of the present study was to
      examine the role of noradrenergic mechanisms in the generation of implicit racial
      attitudes. METHODS: Healthy volunteers (n = 36) of white ethnic origin, received
      a single oral dose of the beta-adrenoceptor antagonist, propranolol (40 mg), in a
      randomised, double-blind, parallel group, placebo-controlled, design.
      Participants completed an explicit measure of prejudice and the racial implicit
      association test (IAT), 1-2 h after propranolol administration. RESULTS: Relative
      to placebo, propranolol significantly lowered heart rate and abolished implicit
      racial bias, without affecting the measure of explicit racial prejudice.
      Propranolol did not affect subjective mood. CONCLUSIONS: Our results indicate
      that beta-adrenoceptors play a role in the expression of implicit racial
      attitudes suggesting that noradrenaline-related emotional mechanisms may mediate
      negative racial bias. Our findings may also have practical importance given that
      propranolol is a widely used drug. However, further studies will be needed to
      examine whether a similar effect can be demonstrated in the course of clinical
      treatment.

PMID- 22371302
TI  - Alcohol affects the emotional modulation of cognitive control: an event-related
      brain potential study.
AB  - OBJECTIVE: The present study aimed to determine whether alcohol affects the
      emotional modulation of cognitive control and its underlying neural mechanisms,
      which is pivotal to an understanding of the socially maladaptive behaviors
      frequently seen in alcohol-intoxicated individuals. METHOD: Event-related
      potentials (ERPs) were recorded in male participants receiving either a moderate
      dose of alcohol (0.65 g/kg alcohol; n = 32) or a non-alcoholic placebo beverage
      (n = 32) while performing an emotional Go/No-Go task that required response
      execution (Go trials) to pictures of a "target" emotional facial expression
      (angry, happy, neutral) and response inhibition (No-Go trials) to a different
      "non-target" expression. RESULTS: Overall, N200 and P300 amplitudes were more
      enhanced during No-Go than Go trials. Interestingly, alcohol-intoxicated
      individuals displayed larger No-Go N200 amplitudes across all emotional
      conditions than controls, accompanied by decreased task performance (i.e., more
      errors), particularly in response to angry faces. P300 amplitude in the alcohol
      group was significantly reduced for both Go and No-Go trials, but only following
      angry and happy emotional expressions. CONCLUSIONS: These results suggest that
      alcohol-intoxicated individuals need to effortfully activate more cognitive
      resources during the early inhibition process in order to regulate a response
      than controls. Moreover, alcohol affected the emotional modulation of both
      response inhibition and execution in the later stages of cognitive control.
      Alcohol dampened emotional responsiveness, which may restrict the availability of
      attentional resources for cognitive control. Yet, these findings may underlie the
      lack of control in alcohol-intoxicated individuals when faced with emotionally or
      socially challenging situations.

PMID- 22371303
TI  - The layer concept: utilization in determining the pain generators, pathology and
      how structure determines treatment.
AB  - The level of understanding of pain in the non-arthritic hip has made significant
      strides in the last couple of decades beginning with the discoveries of Reinhold
      Ganz, MD. However, even with the detection of subtle bony abnormalities,
      including femoroacetabular impingement, a clinician's ability to differentiate
      pain generators in the hip has been ambiguous. Deciphering the etiology of the
      pathology versus the pain generator is essential in prescribing the proper
      treatment. The Layer Concept developed by Dr. Bryan Kelly, is a systematic means
      of determining which structures about the hip are the source of the pathology,
      which are the pain generators and how to then best implement treatment. Four
      layers will be discussed in this article. Layer I, the osseous layer, Layer II,
      the inert tissue layer, Layer III, the contractile layer and Layer IV, the
      neuromechanical layer.

PMID- 22371304
TI  - Characterization of broadband fiber optic line detectors for photoacoustic
      tomography.
AB  - The frequency response of fiber optic line detectors is investigated in the
      presented paper. An analytical model based on oblique scattering of elastic waves
      is used to calculate the frequency dependent acousto-optical transfer functions
      of bare glass optical and polymer optical fibers. From the transfer functions the
      transient response of fibers detectors to photoacoustically excited spherical
      sources is derived. Photoacoustic tomography is simulated by calculating the
      temporal response of arrays of fiber optic line detectors and subsequent image
      reconstruction. The results show that the choice of the fiber material is of
      significant importance and influences the quality of imaging.

PMID- 22371305
TI  - Tetrahydrobiopterin, L-arginine and vitamin C actsynergistically to decrease
      oxidative stress, increase nitricoxide and improve blood flow after induction of
      hindlimbischemia in the rat.
AB  - Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a
      potent vasodilator and signaling molecule that plays an essential role in
      vascular remodeling of collateral arteries and perfusion recovery in response to
      hindlimb ischemia. In ischemic conditions, decreased NO bioavailability was
      observed because of increased oxidative stress, decreased L-arginine and
      tetrahydrobiopterin. This study tested the hypothesis that dietary
      cosupplementation with tetrahydrobiopterin (BH4), L-arginine, and vitamin C acts
      synergistically to decrease oxidative stress, increase nitric oxide and improve
      blood flow in response to acute hindlimb ischemia. Rats were fed normal chow,
      chow supplemented with BH4 or L-arginine (alone or in combination) or chow
      supplemented with BH4 + L-arginine + vitamin C for 1 wk before induction of
      unilateral hindlimb ischemia. Cosupplementation with BH4 + L-arginine resulted in
      greater eNOS expression, Ca2+-dependent NOS activity and NO concentration in
      gastrocnemius from the ischemic hindlimb, as well as greater recovery of foot
      perfusion and more collateral artery enlargement than did rats receiving either
      agent separately. The addition of vitamin C to the BH4 + L-arginine regimen did
      further increase these dependent variables, although only the increase in eNOS
      expression reached statistical significances. In addition, rats given all three
      supplements demonstrated significantly less Ca2+-independent activity, less
      nitrotyrosine accumulation, greater glutathione:glutathione disulfide (GSH:GSSG)
      ratio and less gastrocnemius muscle necrosis, on both macroscopic and microscopic
      levels. In conclusion, cosupplementation with BH4 + L-arginine + vitamin C
      significantly increased vascular perfusion after hindlimb ischemia by increasing
      eNOS activity and reducing oxidative stress and tissue necrosis. Oral
      cosupplementation of L-arginine, BH4 and vitamin C holds promise as a biological
      therapy to induce collateral artery enlargement.

PMID- 22371306
TI  - Dichotomy in Hedgehog signaling between human healthy vessel and atherosclerotic
      plaques.
AB  - The major cause for plaque instability in atherosclerotic disease is
      neoangiogenic revascularization, but the factors controlling this process remain
      only partly understood. Hedgehog (HH) is a morphogen with important functions in
      revascularization, but its function in human healthy vessel biology as well as in
      atherosclerotic plaques has not been well investigated. Hence, we determined the
      status of HH pathway activity both in healthy vessels and atherosclerotic
      plaques. A series of 10 healthy organ donor-derived human vessels, 17 coronary
      atherosclerotic plaques and 24 atherosclerotic carotid plaques were investigated
      for HH pathway activity. We show that a healthy vessel is characterized by a high
      level of HH pathway activity but that atherosclerotic plaques are devoid of HH
      signaling despite the presence of HH ligand in these pathological structures.
      Thus, a dichotomy between healthy vessels and atherosclerotic plaques with
      respect to the activation status of the HH pathway exists, and it is tempting to
      suggest that downregulation of HH signaling contributes to long-term plaque
      stability.

PMID- 22371307
TI  - Dichotomy between RIP1- and RIP3-mediated necroptosis in tumor necrosis factor
      alpha-induced shock.
AB  - Tumor necrosis factor receptor (TNFR) signaling may result in survival, apoptosis
      or programmed necrosis. The latter is called necroptosis if the receptor
      interacting protein 1 (RIP1) inhibitor necrostatin-1 (Nec-1) or genetic knockout
      of RIP3 prevents it. In the lethal mouse model of TNFalpha-mediated shock,
      addition of the pan-caspase inhibitor zVAD-fmk (zVAD) accelerates time to death.
      Here, we demonstrate that RIP3-deficient mice are protected markedly from
      TNFalpha-mediated shock in the presence and absence of caspase inhibition. We
      further show that the fusion protein TAT-crmA, previously demonstrated to inhibit
      apoptosis, also prevents necroptosis in L929, HT29 and FADD-deficient Jurkat
      cells. In contrast to RIP3-deficient mice, blocking necroptosis by Nec-1 or TAT
      crmA did not protect from TNFalpha/zVAD-mediated shock, but further accelerated
      time to death. Even in the absence of caspase inhibition, Nec-1 application led
      to similar kinetics. Depletion of macrophages, natural killer (NK) cells,
      granulocytes or genetic deficiency for T lymphocytes did not influence this
      model. Because RIP3-deficient mice are known to be protected from cerulein
      induced pancreatitis (CIP), we applied Nec-1 and TAT-crmA in this model and
      demonstrated the deterioration of pancreatic damage upon addition of these
      substances. These data highlight the importance of separating genetic RIP3
      deficiency from RIP1 inhibition by Nec-1 application in vivo and challenge the
      current definition of necroptosis.

PMID- 22371308
TI  - Prediction of ischemic events on the basis of transcriptomic and genomic
      profiling in patients undergoing carotid endarterectomy.
AB  - Classic risk factors, including age, smoking, serum cholesterol, diabetes and
      blood pressure, constitute the basis of present risk prediction models but fail
      to identify all individuals at risk. The objective of this study was to
      investigate if genomic and transcriptional patterns improve prediction of
      ischemic events in patients with established carotid artery disease. Genotype and
      gene expression profiles were obtained from carotid plaque tissue (n = 126) and
      peripheral blood mononuclear cells (n = 97) of patients undergoing carotid
      endarterectomy. Patients were followed for an average of 44 months, and 25
      ischemic events occurred (18 ischemic strokes and 7 myocardial infarctions).
      Blinded leave-one-out cross-validation on Cox regression coefficients was used to
      assign gene expression-based risk scores to each patient. When compared with
      classic risk factors, addition of carotid plaque gene expression-based risk score
      improved the prediction of future ischemic events from an area under the curve
      (AUC) of 0.66 to an AUC of 0.79. The inclusion of gene expression risk score from
      peripheral blood mononuclear cells or from 25 established myocardial infarction
      risk single nucleotide polymorphisms only exhibited marginal effects on the
      prediction of ischemic events. Prediction of ischemic events is improved by
      inclusion of gene expression profiling from carotid endarterectomy tissue
      compared with prediction on the basis of classic risk markers alone in patients
      with atherosclerosis. The method may be developed to identify subjects at very
      high risk of ischemic events.

PMID- 22371309
TI  - Age of onset of blindness affects brain anatomical networks constructed using
      diffusion tensor tractography.
AB  - Studying blindness with various onset ages may elucidate the ways that unimodal
      sensory deprivation at different periods of development shape the human brain. In
      order to determine the effect of the onset age on brain anatomical networks, we
      extended a previous study of 17 early blind (EB) subjects with an additional 97
      subjects with various onset ages. We constructed binary anatomical networks of
      these subjects and sighted controls (SC) using diffusion tensor tractography and
      calculated the topological properties of the network. Based on onset age, the
      subjects were divided into congenitally blind (CB), EB, adolescent-blind (AB),
      and late-blind (LB) subgroups. The LB subjects demonstrated a greater
      connectivity density and a higher global efficiency, similar to the SC. The CB
      and EB subgroups showed large group differences from the other groups in their
      topological networks, specifically, a reduced connectivity density and a
      decreased global efficiency compared with the SC, especially in the frontal and
      occipital cortices. Additionally, significant correlations were found between age
      of onset and the topological properties of the anatomical network in the blind.
      Our results suggest that visual experience during an early period of development
      is critical for establishing an intact efficient anatomical network in the human
      brain.

PMID- 22371311
TI  - H3 or H4 histamine receptors: that which contributes to suppressing human
      cholangiocarcinoma progression still remains to be clarified.

PMID- 22371310
TI  - Evoked and intrinsic asymmetries during auditory attention: implications for the
      contralateral and neglect models of functioning.
AB  - Unlike the visual system, a direct mapping of extrapersonal space does not exist
      within human auditory cortex (AC). Thus, models (contralateral bias vs. neglect)
      of how auditory spatial attention is allocated remain debated, as does the role
      of hemispheric asymmetries. To further examine these questions, 27 participants
      completed an exogenous auditory orienting task while undergoing functional
      magnetic resonance imaging. Resting-state data were also collected to
      characterize intrinsic activity within the AC. Current results provide the first
      evidence of hemispheric specialization in the "where" (right secondary AC)
      auditory processing stream during both evoked (orienting task) and intrinsic
      (resting-state data) activity, suggesting that spontaneous and evoked activity
      may be synchronized by similar cortical hierarchies. Strong evidence for a
      contralateral bias model was observed during rapid deployment stages
      (facilitation) of auditory attention in bilateral AC. However, contralateral bias
      increased for left and decreased for right AC (neglect model) after longer
      stimulus onset asynchronies (inhibition of return), suggesting a role for higher
      order cortical structures in modulating AC functioning. Prime candidates for
      attentional modulation include the frontoparietal network, which demonstrated
      right hemisphere lateralization across multiple attentional states.

PMID- 22371312
TI  - Medial versus lateral condyle bone mineral density ratios in a cross-sectional
      study: a potential marker for medial knee osteoarthritis severity.
AB  - OBJECTIVE: To assess the association of bone mineral density (BMD) of the femoral
      and tibial condyles with knee pain and disease severity in women with symptomatic
      medial knee osteoarthritis (OA). METHODS: We enrolled 192 women (ages 41-90
      years) between April 2007 and March 2011. The subjects were divided into 2 groups
      according to joint space narrowing (JSN) on weight-bearing radiographs. BMD of
      the lumbar spine, proximal femur, and knee condyles was measured. Medial and
      lateral condyle BMDs of the femur and tibia as well as the medial versus lateral
      condyle BMD ratios were measured. RESULTS: Mean medial condyle BMDs, medial
      versus lateral condyle BMD ratios, and visual analog scale (VAS) pain in both the
      femur and the tibia were higher in the obliteration group compared with the
      narrowing group (P < 0.001 for all). A significant positive correlation was
      observed between the femoral and tibial condyles in the following parameters:
      medial condyle BMDs, lateral condyle BMDs, and medial versus lateral condyle BMD
      ratios (r = 0.791-0.844). In both the femur and the tibia, medial versus lateral
      condyle BMD ratios had significant positive correlations with femorotibial angle,
      medial osteophytes, lateral osteophytes, medial JSN, and VAS pain, and had
      significant negative correlations with the Knee Society pain and function scores.
      CONCLUSION: Although this study was a cross-sectional study, the femoral and
      tibial medial versus lateral condyle BMD ratios increased with more severe knee
      pain and might be a potential marker for monitoring disease severity in women
      with symptomatic medial knee OA.

PMID- 22371313
TI  - [Doctors for the third world--flexibility is required].

PMID- 22371314
TI  - Principles of phenomics in endometriosis.
AB  - BACKGROUND: Endometriosis has been associated with specific morphometric
      characteristics and pigmentary traits. The purpose of this study was to
      systematically review prior publications dealing with this aspect in order to
      revisit phenotypic information in the context of phenomics principles. METHODS:
      Comprehensive searches of Pubmed, Medline and Embase were conducted to identify
      studies, published from 1990 to 2011 in the English language literature, on the
      relationship between endometriosis and morphometric characteristics/pigmentary
      traits. RESULTS: We identified 11 studies on the association between
      endometriosis and body mass index (BMI) in the adult population and 5 studies on
      the same association during early life. While a modest inverse correlation was
      found between endometriosis and adult BMI, a stronger association was
      consistently demonstrated between endometriosis and early life body size, even
      after adjusting for confounding factors such as age, birthweight, age at
      menarche, parity and oral contraceptive use. Four papers have been published on
      the association between endometriosis and cutaneous naevi and five on the
      association between the disease and specific pigmentary traits. A skin phenotype
      characterized by the presence of naevi and freckles and by a high sensitivity to
      sun exposure is represented more frequently in women with endometriosis.
      CONCLUSIONS: Endometriosis appears to be associated with some phenotypic
      variations likely attributable to the strong effect of the environment on the
      expression and function of genes influencing the traits. Novel clues on
      endometriosis pathogenesis may derive from the analysis of the phenotypic traits
      associated with the disease.

PMID- 22371315
TI  - Aetiology of hypospadias: a systematic review of genes and environment.
AB  - BACKGROUND: Hypospadias is a common congenital malformation of the male external
      genitalia. Most cases have an unknown aetiology, which is probably a mix of
      monogenic and multifactorial forms, implicating both genes and environmental
      factors. This review summarizes current knowledge about the aetiology of
      hypospadias. METHODS: Pubmed was used to identify studies on hypospadias
      aetiology published between January 1995 and February 2011. Reference lists of
      the selected manuscripts were also searched to identify additional studies,
      including those published before 1995. RESULTS: The search provided 922 articles
      and 169 articles were selected for this review. Studies screening groups of
      patients with hypospadias for single gene defects found mutations in WT1, SF1,
      BMP4, BMP7, HOXA4, HOXB6, FGF8, FGFR2, AR, HSD3B2, SRD5A2, ATF3, MAMLD1, MID1 and
      BNC2. However, most investigators are convinced that single mutations do not
      cause the majority of isolated hypospadias cases. Indeed, associations were found
      with polymorphisms in FGF8, FGFR2, AR, HSD17B3, SRD5A2, ESR1, ESR2, ATF3, MAMLD1,
      DGKK, MID1, CYP1A1, GSTM1 and GSTT1. In addition, gene expression studies
      indentified CTGF, CYR61 and EGF as candidate genes. Environmental factors
      consistently implicated in hypospadias are low birthweight, maternal hypertension
      and pre-eclampsia, suggesting that placental insufficiency may play an important
      role in hypospadias aetiology. Exogenous endocrine-disrupting chemicals have the
      potential to induce hypospadias but it is unclear whether human exposure is high
      enough to exert this effect. Other environmental factors have also been
      associated with hypospadias but, for most, the results are inconsistent.
      CONCLUSIONS: Although a number of contributors to the aetiology of hypospadias
      have been identified, the majority of risk factors remain unknown.

PMID- 22371316
TI  - Near-infrared fluorescence imaging of mouse myocardial microvascular endothelium
      using Cy5.5-lectin conjugate.
AB  - Cy5.5-lectin, a non-toxic conjugate, combines the benefits of near-infrared (NIR)
      imaging, such as significant reduction of background fluorescence and increased
      tissue depth penetration, with its affinity for vascular endothelial cells. When
      compared to endothelial staining methods using FITC-lectin and ICAM2 antibodies,
      Cy5.5-lectin was confirmed to specifically bind endothelial cells and produce a
      fluorescence signal both in real-time and post-infusion. Ex-vivo experiments with
      isolated hearts demonstrated that binding was limited to perfused areas of the
      myocardium. With mouse in-vivo tail-vein injections, other organs such as the
      liver, spleen, and kidney were also stained and yielded similar quality images of
      the heart.

PMID- 22371317
TI  - Determining the involvement of two aminopeptidase Ns in the resistance of
      Plutella xylostella to the Bt toxin Cry1Ac: cloning and study of in vitro
      function.
AB  - The cloning, expression in vitro, and characterization of two aminopeptidase Ns
      (APN5s and APN2s) isolated from the midgut of Cry1Ac-resistant (R) and
      susceptible (S) strains of Plutella xylostella larvae are presented in this
      paper. The deduced amino acid sequences of APN5s included C-terminal GPI
      modification sites, the gluzincin aminopeptidase motif GATEN, and three N
      glycosylated sites; those of APN2s had no GPI-modification sites, had gluzincin
      aminopeptidase motif GAMEN, and had four N-glycosylated sites. O-glycosylated
      sites were not predicted for either APN. Because APN2R and APN2S cDNAs contained
      the same nucleotides, only full-length cDNAs encoding APN5R and APN5S were
      expressed in Trichoplusia ni cells. Far-Western blotting showed that the
      expressed receptor APN5 bound to the Cry1Ac toxin. An enzyme-specific activity
      experiment also showed that APN5 genes were expressed in T. ni cells. ELISA
      revealed no differences in the binding of expression proteins from the resistant
      and susceptible strain with Cry1Ac.

PMID- 22371318
TI  - Is the M probe really necessary to measure liver stiffness by FibroScan?

PMID- 22371320
TI  - Nanoscale distinction of membrane patches--a TERS study of Halobacterium
      salinarum.
AB  - The structural organization of cellular membranes has an essential influence on
      their functionality. The membrane surfaces currently are considered to consist of
      various distinct patches, which play an important role in many processes,
      however, not all parameters such as size and distribution are fully determined.
      In this study, purple membrane (PM) patches isolated from Halobacterium salinarum
      were investigated in a first step using TERS (tip-enhanced Raman spectroscopy).
      The characteristic Raman modes of the resonantly enhanced component of the purple
      membrane lattice, the retinal moiety of bacteriorhodopsin, were found to be
      suitable as PM markers. In a subsequent experiment a single Halobacterium
      salinarum was investigated with TERS. By means of the PM marker bands it was
      feasible to identify and localize PM patches on the bacterial surface. The size
      of these areas was determined to be a few hundred nanometers.

PMID- 22371319
TI  - Phase II study of Gleevec plus hydroxyurea in adults with progressive or
      recurrent low-grade glioma.
AB  - BACKGROUND: We evaluated the efficacy of imatinib plus hydroxyurea in patients
      with progressive/recurrent low-grade glioma. METHODS: A total of 64 patients with
      recurrent/progressive low-grade glioma were enrolled in this single-center study
      that stratified patients into astrocytoma and oligodendroglioma cohorts. All
      patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at
      400 mg per day for patients not on enzyme-inducing antiepileptic drugs (EIAEDs)
      and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free
      survival at 12 months (PFS-12) and secondary endpoints were safety, median
      progression-free survival, and radiographic response rate. RESULTS: Thirty-two
      patients were enrolled into each cohort. Eleven patients (17%) had before
      radiotherapy and 24 (38%) had received before chemotherapy. The median PFS and
      PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the
      histologic cohorts. No patient achieved a radiographic response. The most common
      grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%),
      and diarrhea (3%). CONCLUSIONS: Imatinib plus hydroxyurea was well tolerated
      among recurrent/progressive LGG patients but this regimen demonstrated negligible
      antitumor activity.

PMID- 22371322
TI  - Social relationships and social roles.
AB  - This review draws attention to the broad and diverse theoretical underpinnings of
      interpersonal psychotherapy (IPT). A plea is made for greater attention to the
      theoretical influences on IPT in forming our understanding of the techniques and
      processes and to establish indicators of successful outcome as well as for whom
      the treatment is most suitable. The paper takes a lifespan perspective that
      considers the implications of social factors for the different age groups to
      which IPT has been shown to be effective in the treatment of depression. The main
      thrust of the paper considers the potential importance of social theory,
      particularly the research on life events and social support. It is argued that it
      is these social aspects and particularly a focus on the use of the patient's
      wider social network that distinguishes IPT from other evidence-based short-term
      therapies. KEY PRACTITIONER MESSAGE: Interpersonal psychotherapy draws on a broad
      and diverse range of theoretical influences. The study of the theory underpinning
      IPT can inform assessment, technique and process in the practice of IPT.
      Knowledge of aspects of the research on life events and social support is
      particularly relevant not only for the assessment phase but also for the middle
      and termination phases. Attention to the theory behind IPT can usefully inform
      future research on IPT particularly what may determine successful or unsuccessful
      outcome of this short-term treatment.

PMID- 22371321
TI  - Spectrum of congenital anomalies in pregnancies with pregestational diabetes.
AB  - BACKGROUND: Maternal pregestational diabetes is a well-known risk factor for
      congenital anomalies. This study analyses the spectrum of congenital anomalies
      associated with maternal diabetes using data from a large European database for
      the population-based surveillance of congenital anomalies. METHODS: Data from 18
      population-based EUROCAT registries of congenital anomalies in 1990-2005. All
      malformed cases occurring to mothers with pregestational diabetes (diabetes
      cases) were compared to all malformed cases in the same registry areas to mothers
      without diabetes (non-diabetes cases). RESULTS: There were 669 diabetes cases and
      92,976 non diabetes cases. Odds ratios in diabetes pregnancies relative to non
      diabetes pregnancies comparing each EUROCAT subgroup to all other non-chromosomal
      anomalies combined showed significantly increased odds ratios for neural tube
      defects (anencephaly and encephalocele, but not spina bifida) and several
      subgroups of congenital heart defects. Other subgroups with significantly
      increased odds ratios were anotia, omphalocele and bilateral renal agenesis.
      Frequency of hip dislocation was significantly lower among diabetes (odds ratio
      0.15, 95% CI 0.05-0.39) than non-diabetes cases. Multiple congenital anomalies
      were present in 13.6 % of diabetes cases and 6.1 % of non-diabetes cases. The
      odds ratio for caudal regression sequence was very high (26.40,95% CI 8.98
      77.64), but only 17% of all caudal regression cases resulted from a pregnancy
      with pregestational diabetes. CONCLUSIONS: The increased risk of congenital
      anomalies in pregnancies with pregestational diabetes is related to specific non
      chromosomal congenital anomalies and multiple congenital anomalies and not a
      general increased risk.

PMID- 22371323
TI  - Plastid lipid droplets at the crossroads of prenylquinone metabolism.
AB  - Lipid droplets called plastoglobules (PGs) exist in most plant tissues and
      plastid types. In chloroplasts, the polar lipid monolayer surrounding these low
      density lipoprotein particles is continuous with the outer lipid leaflet of the
      thylakoid membrane. Often small clusters of two or three PGs, only one of them
      directly connected to thylakoids, are present. Structural proteins (known as
      plastid-lipid associated proteins/fibrillins or plastoglobulins) together with
      lipid metabolic enzymes coat the PGs. The hydrophobic core of PGs contains a
      range of neutral lipids including the prenylquinones [tocopherols (vitamin E),
      phylloquinone (vitamin K(1)), and plastoquinone (PQ-9)]. In this review the
      function of PGs and their associated enzymes in prenylquinone metabolism will be
      discussed.

PMID- 22371324
TI  - Photosynthetic control of electron transport and the regulation of gene
      expression.
AB  - The term 'photosynthetic control' describes the short- and long-term mechanisms
      that regulate reactions in the photosynthetic electron transport (PET) chain so
      that the rate of production of ATP and NADPH is coordinated with the rate of
      their utilization in metabolism. At low irradiances these mechanisms serve to
      optimize light use efficiency, while at high irradiances they operate to
      dissipate excess excitation energy as heat. Similarly, the production of ATP and
      NADPH in ratios tailored to meet demand is finely tuned by a sophisticated series
      of controls that prevents the accumulation of high NAD(P)H/NAD(P) ratios and
      ATP/ADP ratios that would lead to potentially harmful over-reduction and
      inactivation of PET chain components. In recent years, photosynthetic control has
      also been extrapolated to the regulation of gene expression because mechanisms
      that are identical or similar to those that serve to regulate electron flow
      through the PET chain also coordinate the regulated expression of genes encoding
      photosynthetic proteins. This requires coordinated gene expression in the
      chloroplasts, mitochondria, and nuclei, involving complex networks of forward and
      retrograde signalling pathways. Photosynthetic control operates to control
      photosynthetic gene expression in response to environmental and metabolic
      changes. Mining literature data on transcriptome profiles of C(3) and C(4) leaves
      from plants grown under high atmospheric carbon dioxide (CO(2)) levels compared
      with those grown with ambient CO(2) reveals that the transition to higher
      photorespiratory conditions in C(3) plants enhances the expression of genes
      associated with cyclic electron flow pathways in Arabidopsis thaliana, consistent
      with the higher ATP requirement (relative to NADPH) of photorespiration.

PMID- 22371325
TI  - The expression of phototropins in Arabidopsis leaves: developmental and light
      regulation.
AB  - Phototropins are blue light receptors, which play different roles during plant
      development. Two phototropins of Arabidopsis thaliana, phot1 and phot2, have
      strongly overlapping functions. In seedlings, both photoreceptors are responsible
      for phototropism. In mature leaves they redundantly regulate leaf shape, stomatal
      opening, and the accumulation of chloroplasts, whereas phototropin2 alone
      controls chloroplast avoidance response. Light not only activates phototropins,
      but also affects the level of their expression. In Arabidopsis seedlings, PHOT1
      is downregulated and PHOT2 is upregulated by light. Since data on transcription
      levels of phototropins in mature Arabidopsis leaves is scarce, a comprehensive
      real-time PCR study of PHOT1 and PHOT2 expression during development was
      performed, from seedlings to senescing leaves. So far, neither the phototropin
      expression nor its modulation by light have been investigated during senescence.
      The results show that the general regulation pattern remains conserved during
      Arabidopsis lifecycle, whereas the level of transcripts fluctuates over time,
      pointing to the significance of the light control for functioning of
      phototropins. The second part of the study determined the influence of
      photosynthesis-derived signals and photoreceptor-activated transduction pathways
      on phototropin mRNA levels. The effects of blue and red light were examined using
      Arabidopsis mutant lines deficient in photoreceptors. The results reveal a
      complex network of interactions between these receptors in the regulation of
      phototropin transcription profiles. Cryptochrome1 and phytochromeB appear to be
      main photoreceptors involved in the regulation of PHOT1 transcript accumulation.
      The expression of PHOT2 is dependent on both cryptochromes and phytochromeA.

PMID- 22371326
TI  - Inhibition of aconitase by nitric oxide leads to induction of the alternative
      oxidase and to a shift of metabolism towards biosynthesis of amino acids.
AB  - Nitric oxide (NO) is a free radical molecule involved in signalling and in
      hypoxic metabolism. This work used the nitrate reductase double mutant of
      Arabidopsis thaliana (nia) and studied metabolic profiles, aconitase activity,
      and alternative oxidase (AOX) capacity and expression under normoxia and hypoxia
      (1% oxygen) in wild-type and nia plants. The roots of nia plants accumulated very
      little NO as compared to wild-type plants which exhibited ~20-fold increase in NO
      emission under low oxygen conditions. These data suggest that nitrate reductase
      is involved in NO production either directly or by supplying nitrite to other
      sites of NO production (e.g. mitochondria). Various studies revealed that NO can
      induce AOX in mitochondria, but the mechanism has not been established yet. This
      study demonstrates that the NO produced in roots of wild-type plants inhibits
      aconitase which in turn leads to a marked increase in citrate levels. The
      accumulating citrate enhances AOX capacity, expression, and protein abundance. In
      contrast to wild-type plants, the nia double mutant failed to show AOX induction.
      The overall induction of AOX in wild-type roots correlated with accumulation of
      glycine, serine, leucine, lysine, and other amino acids. The findings show that
      NO inhibits aconitase under hypoxia which results in accumulation of citrate, the
      latter in turn inducing AOX and causing a shift of metabolism towards amino acid
      biosynthesis.

PMID- 22371327
TI  - Diagnostic accuracy of adipose insulin resistance index and visceral adiposity
      index for progressive liver histology and cardiovascular risk in nonalcoholic
      fatty liver disease.

PMID- 22371329
TI  - Toward systems biology of pulmonary hypertension.

PMID- 22371328
TI  - MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension:
      results of a network bioinformatics approach.
AB  - BACKGROUND: Pulmonary hypertension (PH) is driven by diverse pathogenic
      etiologies. Owing to their pleiotropic actions, microRNA molecules are potential
      candidates for coordinated regulation of these disease stimuli. METHODS AND
      RESULTS: Using a network biology approach, we identify microRNA associated with
      multiple pathogenic pathways central to PH. Specifically, microRNA-21 (miR-21) is
      predicted as a PH-modifying microRNA, regulating targets integral to bone
      morphogenetic protein (BMP) and Rho/Rho-kinase signaling as well as functional
      pathways associated with hypoxia, inflammation, and genetic haploinsufficiency of
      BMP receptor type 2. To validate these predictions, we have found that hypoxia
      and BMP receptor type 2 signaling independently upregulate miR-21 in cultured
      pulmonary arterial endothelial cells. In a reciprocal feedback loop, miR-21
      downregulates BMP receptor type 2 expression. Furthermore, miR-21 directly
      represses RhoB expression and Rho-kinase activity, inducing molecular changes
      consistent with decreased angiogenesis and vasodilation. In vivo, miR-21 is
      upregulated in pulmonary tissue from several rodent models of PH and in humans
      with PH. On induction of disease in miR-21-null mice, RhoB expression and Rho
      kinase activity are increased, accompanied by exaggerated manifestations of PH.
      CONCLUSIONS: A network-based bioinformatic approach coupled with confirmatory in
      vivo data delineates a central regulatory role for miR-21 in PH. Furthermore,
      this study highlights the unique utility of network biology for identifying
      disease-modifying microRNA in PH.

PMID- 22371330
TI  - Integrated multimodal optical microscopy for structural and functional imaging of
      engineered and natural skin.
AB  - An integrated multimodal optical microscope is demonstrated for high-resolution,
      structural and functional imaging of engineered and natural skin. This microscope
      incorporates multiple imaging modalities including optical coherence (OCM), multi
      photon (MPM), and fluorescence lifetime imaging microscopy (FLIM), enabling
      simultaneous visualization of multiple contrast sources and mechanisms from cells
      and tissues. Spatially co-registered OCM/MPM/FLIM images of multi-layered skin
      tissues are obtained, which are formed based on complementary information
      provided by different modalities, i.e., scattering information from OCM,
      molecular information from MPM, and functional cellular metabolism states from
      FLIM. Cellular structures in both the dermis and epidermis, especially different
      morphological and physiological states of keratinocytes from different epidermal
      layers, are revealed by mutually-validating images. In vivo imaging of human skin
      is also investigated, which demonstrates the potential of multimodal microscopy
      for in vivo investigation during engineered skin engraftment. This integrated
      imaging technique and microscope show the potential for investigating cellular
      dynamics in developing engineered skin and following in vivo grafting, which will
      help refine the control and culturing conditions necessary to obtain more robust
      and physiologically-relevant engineered skin substitutes.

PMID- 22371331
TI  - Glutathione peroxidase tagSNPs: associations with rectal cancer but not with
      colon cancer.
AB  - Glutathione peroxidases (GPXs) are selenium-dependent enzymes that reduce and,
      thus, detoxify hydrogen peroxide and a wide variety of lipid hydroperoxides. We
      investigated tagSNPs in GPX1-4 in relation to colorectal neoplasia in three
      independent study populations capturing the range of colorectal carcinogenesis
      from adenoma to cancer. A linkage-disequilibrium (LD)-based tagSNP selection
      algorithm (r(2) >= 0.90, MAF >= 4%) identified 21 tagSNPs. We used an identical
      Illumina platform to genotype GPX SNPs in three population-based case-control
      studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583
      cases/775 controls), and colorectal adenomas (485 cases/578 controls). For gene
      level associations, we conducted principal component analysis (PCA); multiple
      logistic regression was used for single SNPs. Analyses were adjusted for age,
      sex, and study center and restricted to non-Hispanic white participants. Analyses
      of cancer endpoints were stratified by molecular subtypes. Without correction for
      multiple testing, one polymorphism in GPX2 and three polymorphisms in GPX3 were
      associated with a significant risk reduction for rectal cancer at alpha = 0.05,
      specifically for rectal cancers with TP53 mutations. The associations regarding
      the three polymorphisms in GPX3 remained statistically significant after
      adjustment for multiple comparisons. The PCA confirmed an overall association of
      GPX3 with rectal cancer (P = 0.03). No other statistically significant
      associations were observed. Our data provide preliminary evidence that genetic
      variability in GPX3 contributes to risk of rectal cancer but not of colon cancer
      and thus provide additional support for differences in underlying pathogenetic
      mechanisms for colon and rectal cancer.

PMID- 22371332
TI  - Is maternal parity an independent risk factor for birth defects?
AB  - BACKGROUND: Although associations between maternal parity and birth defects have
      been observed previously, few studies have focused on the possibility that parity
      is an independent risk factor for birth defects. We investigated the relation
      between levels of parity and a range of birth defects, adjusting each defect
      group for the same covariates. METHODS: We included infants who had an estimated
      delivery date between 1997 and 2007 and participated in the National Birth
      Defects Prevention Study, a multisite case-control study. Cases included infants
      or fetuses belonging to 38 phenotypes of birth defects (n = 17,908), and controls
      included infants who were unaffected by a major birth defect (n = 7173). Odds
      ratios (ORs) were adjusted for 12 covariates using logistic regression. RESULTS:
      Compared with primiparous mothers, nulliparous mothers were more likely to have
      infants with amniotic band sequence, hydrocephaly, esophageal atresia,
      hypospadias, limb reduction deficiencies, diaphragmatic hernia, omphalocele,
      gastroschisis, tetralogy of Fallot, and septal cardiac defects, with significant
      ORs (1.2 to 2.3). Compared with primiparous mothers, multiparous mothers had a
      significantly increased risk of omphalocele, with an OR of 1.5, but had
      significantly decreased risk of hypospadias and limb reduction deficiencies, with
      ORs of 0.77 and 0.77. CONCLUSIONS: Nulliparity was associated with an increased
      risk of specific phenotypes of birth defects. Most of the phenotypes associated
      with nulliparity in this study were consistent with those identified by previous
      studies. Research into biologic or environmental factors that are associated with
      nulliparity may be helpful in explaining some or all of these associations.

PMID- 22371333
TI  - Cross-cultural opening in German outpatient mental healthcare service: an
      exploratory study of structural and procedural aspects.
AB  - Mental healthcare services need to be sensitive towards the cultural needs of
      patients. Cross-cultural opening is an organizational process to fulfil these
      needs. This study aims to provide representative structural and procedural data
      regarding the use of German outpatient mental healthcare services by
      allochthonous patients, the diversity of psychotherapists in outpatient mental
      healthcare service, the cross-cultural encounters of therapists and the cross
      cultural sensitivity of psychotherapists working in this healthcare area. Of all
      public outpatient psychotherapists in Hamburg, 81% (n = 485) participated in this
      survey. Regarding the distribution of the population in this metropolis,
      allochthonous therapists were underrepresented. Unlike the overall distribution
      of foreign inhabitants, the largest groups of immigrant therapists came from
      England, German-speaking countries and other countries within the European Union.
      The proportion of allochthonous patients in outpatient mental healthcare service
      was almost half of the proportion of the allochthonous in the general population.
      Psychotherapists with a migration background regarded themselves as having a
      higher level of cross-cultural sensitivity than their native colleagues,
      especially those who have had fewer cross-cultural encounters. Overall,
      psychotherapists named different challenges in providing cross-cultural
      treatment. For the German outpatient mental healthcare service to be more
      accessible to immigrants and their descendants, a greater number of bilingual
      psychotherapists must gain access to the mental healthcare service, and more
      advanced cross-cultural sensitivity training and supervision should be provided.
      KEY PRACTITIONER MESSAGE: German outpatient psychotherapists are culturally and
      linguistically diverse. Nevertheless, psychotherapists with a migration
      background are underrepresented in outpatient mental healthcare services.
      Patients with a migration background are also underrepresented in the German
      outpatient mental healthcare system. Because mental healthcare services must be
      sensitive and respectful towards patients' cultural and linguistic needs, the
      mental healthcare outpatient service must be more accessible to therapists who
      speak languages other than German and English. Psychotherapeutic treatment of
      patients with a migration background can be tremendously challenging because of
      other cultures' differing value systems. Prospective, advanced training in cross
      cultural sensitivity and cross-cultural supervision should be provided.

PMID- 22371334
TI  - Long-term trends in food availability, food prices, and obesity in Samoa.
AB  - OBJECTIVES: To describe long-term food availability and prices from 1961 to 2007
      and body mass index (BMI) trends from 1980 to 2010 in Samoa, and to contextualize
      these trends within political, economic, cultural, behavioral, and climatic
      influences. METHODS: National level data on food availability and pricing were
      obtained from the open access database FAO (http://faostat.fao.org). Data for
      Samoa were collected from annual food balance sheets available for the period
      1961-2007. Mean BMI for Samoan men and women aged 35-44 years of age is reported
      from four different time periods, 1979-1982, 1991, 2003, and 2010. RESULTS: Total
      energy availability increased substantially, by 47%, with more than 900 extra
      calories available per capita per day in 2007 than in 1961. Many of these extra
      calories are supplied by dietary fat, the availability of which rose by a
      proportionally greater amount, 73%. Availability of both meat and vegetable oils
      rose substantially. Poultry meat increased the most proportionally, from 10 to
      117 kcal per capita per day. Coconut products, fruits, and starchy root crops-all
      locally grown-showed little to no increase over this time. As import prices for
      poultry and mutton increased their availability decreased, but the availability
      of vegetable oils rose despite a rise in their price. Mean BMI for men and women
      aged 35-44 years rose 18% rise from 1980 to 2010. CONCLUSIONS: These long-term
      trends in food availability and prices, and the temporal pattern of BMI provide
      national level data for understanding the process of the nutritional transition
      in Samoa. Further work on consumer food prices, diet, food security, and health
      is needed to further contextualize the transformation of the local food system in
      Samoa.

PMID- 22371335
TI  - A TDDFT investigation of bay substituted perylenediimides: absorption and
      intersystem crossing.
AB  - The conformational structure and electronic spectra properties of a series of bay
      substituted perylenediimides (PDI) derivatives have been investigated by means of
      density functional theory (DFT) and time-dependent DFT. The B3LYP and PBE0 hybrid
      exchange-correlation functionals were applied in conjunction with the double-zeta
      quality SVP basis set. These compounds are interesting for organic materials
      science and as photosensitizers in cancer phototherapy (PDT), because of their
      intense absorption in the visible region. Results show that the substitution at
      the bay position of the PDI parent molecule with N-alkyl groups shifts the
      absorption maxima towards the red part of the visible spectrum (around 650-700
      nm) as required for the applications in PDT. The main PDT action mechanisms have
      been investigated by computing of electron affinities, ionization potentials,
      triplet energies and spin-orbit matrix elements between singlet and triplet
      excited states.

PMID- 22371336
TI  - Delineation of commonly deleted chromosomal regions in meningiomas by high
      density single nucleotide polymorphism genotyping arrays.
AB  - Despite recent advances in the identification of the cytogenetic profiles of
      meningiomas, a significant group of tumors still show normal karyotypes or few
      chromosomal changes. The authors analyzed the cytogenetic profile of 50
      meningiomas using fluorescence in situ hybridization and high-density (500 K)
      single nucleotide polymorphism (SNP) arrays. Our results confirm that del(22q)
      (52%) and del(1p) (16%) (common deleted regions: 22q11.21-22q13.3. and 1p31.2
      p36.33) are the most frequent alterations. Additionally, recurrent monosomy 14
      (8%), del(6q) (10%), del(7p) (10%), and del(19q) (4%) were observed, while copy
      number patterns consistent with recurrent chromosomal gains, gene amplification,
      and copy number neutral loss of heterozygosity (cnLOH) were either absent or
      rare. Based on their overall SNP profiles, meningiomas could be classified into:
      (i) diploid cases, (ii) meningiomas with a single chromosomal change [e.g.,
      monosomy 22/del(22q)] and (iii) tumors with >=2 altered chromosomes. In summary,
      our results confirm and extend on previous observations showing that the most
      recurrent chromosomal abnormalities in meningiomas correspond to chromosome
      losses localized in chromosomes 1, 22 and less frequently in chromosomes 6, 7,
      14, and 19, while chromosomal gains and cnLOH are restricted to a small
      proportion of cases. Finally, a set of cancer-associated candidate genes
      associated with the TP53, MYC, CASP3, HDAC1, and TERT signaling pathways was
      identified, in cases with coexisting monosomy 14 and del(1p).

PMID- 22371337
TI  - TGF-beta1 enhances contractility in engineered skeletal muscle.
AB  - Scaffoldless engineered 3D skeletal muscle tissue created from satellite cells
      offers the potential to replace muscle tissue that is lost due to severe trauma
      or disease. Transforming growth factor-beta 1 (TGF-beta1) plays a vital role in
      mediating migration and differentiation of satellite cells during the early
      stages of muscle development. Additionally, TGF-beta1 promotes collagen type I
      synthesis in the extracellular matrix (ECM) of skeletal muscle, which provides a
      passive elastic substrate to support myofibres and facilitate the transmission of
      force. To determine the role of TGF-beta1 in skeletal muscle construct formation
      and contractile function in vitro, we created tissue-engineered 3D skeletal
      muscle constructs with varying levels of recombinant TGF-beta1 added to the cell
      culture medium. Prior to the addition of TGF-beta1, the primary cell population
      was composed of 75% Pax7-positive cells. The peak force for twitch, tetanus and
      spontaneous force were significantly increased in the presence of 2.0 ng/ml TGF
      beta1 when compared to 0, 0.5 and 1.0 ng/ml TGF-beta1. Visualization of the
      cellular structure with H&E and with immunofluorescence staining for sarcomeric
      myosin heavy chains and collagen type I showed denser regions of better organized
      myofibres in the presence of 2.0 ng/ml TGF-beta1 versus 0, 0.5 and 1.0 ng/ml. The
      addition of 2.0 ng/ml TGF-beta1 to the culture medium of engineered 3D skeletal
      muscle constructs enhanced contractility and extracellular matrix organization.

PMID- 22371339
TI  - Attachment and socio-emotional skills: a comparison of depressed inpatients,
      institutionalized delinquents and control adolescents.
AB  - This study compared 50 depressed inpatients, 51 institutionalized delinquents and
      51 control adolescents (total n = 152) regarding attachment and associated socio
      emotional skills. All of the participants took an individual interview (i.e.,
      anamnesis, diagnostic interview and intelligence test) and completed the
      attachment measure and self-report measures of socio-emotional skills (i.e.,
      emotional intelligence, empathy and resilience). Results showed that controls
      scored higher on secure attachment, whereas both of the other groups scored
      higher on preoccupied attachment. Depressed adolescents had lower scores on
      emotional intelligence than did controls. Finally, depressed adolescents had
      lower scores than the other two groups on resilience. The anxious or preoccupied
      attachment in both clinical groups, the overall frailty of depressive adolescents
      and the apparent resilience of delinquent adolescents despite their cognitive
      limitations should inform the respective treatment plans for these groups of
      adolescents. Suggestions for future research into differences between depressed
      and delinquent adolescents are outlined. KEY PRACTITIONER MESSAGE: Both depressed
      and delinquent adolescents show more anxious attachment. Depressed adolescents
      are less resilient than delinquent adolescents. Delinquent adolescents are less
      intelligent than the other two groups but well-adjusted overall. These
      differences should inform treatment plans for these two clinical groups.

PMID- 22371340
TI  - Modified hemi-Lothrop procedure for supraorbital frontal sinus access: a case
      series.

PMID- 22371338
TI  - Strain-specific modifier genes governing craniofacial phenotypes.
AB  - BACKGROUND: The presence of strain-specific modifier genes is known to modulate
      the phenotype and pathophysiology of mice harboring genetically engineered
      mutations. Thus, identification of genetic modifier genes is requisite to
      understanding control of phenotypic expression. c-Ski is a transcriptional
      regulator. Ski(-/-) mice on a C57BL6J (B6) background exhibit facial clefting,
      while Ski(-/-) mice on a 129P3 (129) background present with exencephaly.
      METHODS: In the present study, oligonucleotide-based gene expression profiling
      was used to identify potential strain-specific modifier gene candidates present
      in wild type mice of B6 and 129 genetic backgrounds. Changes in gene expression
      were verified by TaqMan quantitative real-time PCR. RESULTS: Steady-state levels
      of 89 genes demonstrated a significantly higher level of expression, and those of
      68 genes demonstrated a significantly lower level of expression in the developing
      neural tubes from embryonic day (E) 8.5, B6 embryos when compared to expression
      levels in neural tubes derived from E 8.5, 129 embryos. CONCLUSIONS: Based on the
      results from the current comparative microarray study, and taking into
      consideration a number of relevant published reports, several potential strain
      specific gene candidates, likely to modify the craniofacial phenotypes in various
      knockout mouse models have been identified.

PMID- 22371341
TI  - Mastoidectomy cavity obliteration with bioactive glass: a pilot study.
AB  - OBJECTIVE: To show that mastoid cavities with continuous infections and cleaning
      problems can be obliterated with bioactive glass (BG) and to present results of a
      pilot study for 16 operations on adults. STUDY DESIGN: Case series with planned
      data collection. SETTING: Paijat-Hame Central Hospital, Finland-a single ear,
      nose, and throat (ENT) hospital department serving a population of 216,000.
      SUBJECTS AND METHODS: Fourteen patients had a large open radical cavity with
      recurrent infections. Two ears had discharge and pain after simple mastoidectomy.
      A re-mastoidectomy included support of the cavity skin and obliteration with BG.
      The mean follow-up time was 2.2 years. RESULTS: All ears became dry. One
      reoperation was needed as the fascia support to the ear canal (EC) skin was too
      weak, and part of the BG leaked into the EC. The ear stayed dry, and the missing
      BG was replaced in a reoperation. A slightly short musculoperiosteal flap
      supported the EC skin in 1 ear. A minor amount of BG leaked into the EC. The ear
      stayed dry. The aim was an ample ear canal. One ear was overfilled and required
      meatoplasty. Simple mastoid cavities were isolated from the middle ear and become
      asymptomatic. CONCLUSIONS: In this pilot study, BG works safely and with success
      as an obliteration material in problematic open radical cavities. Bioactive glass
      seems to tolerate chronic infection in the mastoid and prevent postoperative
      infections.

PMID- 22371342
TI  - Qualitative and quantitative differences between 2 robotic thyroidectomy
      techniques.
AB  - OBJECTIVES: Two distinct remote access robotic thyroidectomy techniques were
      implemented in a high-volume endocrine surgery practice. Important technical and
      clinical differences were observed and are described. STUDY DESIGN: Cross
      sectional study with planned data collection. SETTING: Thyroid center. SUBJECTS
      AND METHODS: A panel of demographic and clinical parameters was captured in a
      series of patients undergoing 1 of 2 robotic thyroidectomy techniques (robotic
      axillary thyroidectomy [RAT] or robotic facelift thyroidectomy [RFT]). Particular
      attention was paid to time of surgery, ease of dissection, complications, use of
      drains, and length of stay. RESULTS: Fifteen robotic hemithyroidectomies were
      accomplished by either RAT (n = 5) or RFT (n = 10). The duration of surgery for
      RAT averaged 196 +/- 38.1 minutes, with no clear downward trend observed. The
      mean time of surgery for RFT was 156.9 +/- 16.3 minutes, with a steady trend
      toward shorter surgical times. All 5 RAT patients were managed with drains and as
      inpatients (length of stay = 1.0 days); 9 of 10 RFT patients were managed without
      drains and on an outpatient basis (the first patient had a drain and was observed
      for 1 night in the hospital; P < .001). Ease of surgery, familiarity with
      anatomic dissection planes, and surgeon comfort level all favored RFT.
      CONCLUSIONS: In an early experience of a small series of patients, a more rapid
      learning curve reflected by shorter operative times was observed with robotic
      facelift thyroidectomy compared with robotic axillary thyroidectomy. Furthermore,
      the vast majority of patients could be managed as outpatients, which represents
      one of several apparent advantages.

PMID- 22371343
TI  - Tympanostomy tube in vitro biofilm potential of common otopathogens.
AB  - OBJECTIVE: Post-tympanostomy tube otorrhea has been linked to microbial biofilms.
      The purpose of this study was to compare the tympanostomy tube-biofilm-forming
      propensity of common otopathogens Pseudomonas aeruginosa, Staphylococcus aureus,
      Haemophilus influenzae, and Streptococcus pneumoniae. STUDY DESIGN: Controlled,
      in vitro. SETTING: Academic research laboratory. SUBJECTS AND METHODS:
      Fluoroplastic coupons (1656 total, 46 per treatment per incubation period) were
      exposed to plasma and cultured with 3 strains each of the bacterial species for
      2, 4, or 7 days. Half of the coupons were treated with antibiotics to kill
      planktonic bacteria. Total and biofilm colony counts and electron microscopy were
      performed. RESULTS: S aureus formed biofilm after 2 days, not different from 4-
      or 7-day biofilms (P > .05), and was most tolerant to antibiotic treatment. P
      aeruginosa also formed biofilms at 2 days, reached a plateau at 4 days (P > .05),
      and decreased at 7 days (P < .01). H influenzae formed biofilm only after 4 days
      (P <= .04). S pneumoniae did not form biofilm without catalase supplementation.
      With catalase, 1 S pneumoniae strain showed a delay in biofilm formation similar
      to H influenzae (P < .0001), while the other 2 strains formed biofilms after 2
      days. CONCLUSIONS: Tympanostomy tube biofilm formation occurs with common middle
      ear pathogens but most readily with S aureus and P aeruginosa. Further
      investigation is needed to determine if these findings may, in part, explain the
      occasionally refractory nature of post-tympanostomy tube otorrhea associated with
      S aureus and P aeruginosa.

PMID- 22371344
TI  - Trends in total laryngectomy in the era of organ preservation: a population-based
      study.
AB  - OBJECTIVE: To describe time trends in total laryngectomy health services
      utilization across the United States, such as rates of surgery, cost, length of
      stay, and insurance payer, and to compare this to important milestones in
      recommendations for laryngeal cancer treatment. STUDY DESIGN: Population-based
      cohort study. SETTING: Healthcare Cost and Utilization Project-Nationwide
      Inpatient Sample (HCUP-NIS) 1997-2008: stratified sample of all US hospital
      discharges. SUBJECTS AND METHODS: All patients with the principal procedure of
      complete laryngectomy. The unit of analysis was the discharge. RESULTS: Between
      1997 and 2008, the number of laryngectomies done in the United States decreased
      by 48%. New cases of laryngeal cancer decreased 33% during the same time. The
      proportion of patients older than 65 years decreased from 48% to 43%. Mortality
      for the procedure was 1.4% in 1997 and 1.1% in 2008. Mean length of stay over the
      study period increased from 13 days to 14 days. Mean hospital charges rose from
      $58,000 in 1997 to $109,000 in 2008, consistent with the overall rise in US
      health care costs. Medicare was the dominant insurer throughout. Home health was
      ordered in 50% of 2008 discharges but only 32% in 1997. CONCLUSIONS: The rate of
      total laryngectomy has dropped more than the incidence of laryngeal cancer has
      dropped, consistent with the trend toward nonsurgical treatment. Lower surgical
      volumes and/or salvage laryngectomy surgeries are hypothesized to play a role in
      longer length of stay, stable mortality rates despite younger patient age, and
      increased need for home services after discharge.

PMID- 22371345
TI  - Extraordinary adult thyroglossal duct cyst.

PMID- 22371346
TI  - Isolated skip nodal metastasis is rare in T1 and T2 oral tongue squamous cell
      carcinoma.
AB  - OBJECTIVE: Nodal metastasis from oral tongue squamous cell carcinoma follows a
      predictable pattern. Isolated level IV involvement, termed skip metastases, is
      described. This study attempts to identify the incidence of skip metastasis.
      STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic hospital.
      SUBJECTS: Fifty-two consecutive patients with T1 to T4 N0 stage who underwent
      excision of the primary tumor with neck dissection (levels I-IV). METHODS:
      Retrospective study. The incidence of isolated level III or IV involvement
      pathologically and isolated nodal recurrence in levels III and IV was analyzed.
      RESULTS: Pathologically, isolated level III involvement occurred in 2 (3.8%)
      patients. Isolated level IV occurred in 1 (1.9%) patient. Mean follow-up was 24
      months. Two patients had recurrence in the primary site; 1 had recurrence in neck
      level II. None had recurrence in level III or IV. CONCLUSION: Skip metastasis is
      rare in T1 and T2 oral tongue squamous cell carcinoma. Inclusion of level IV is
      not mandatory in selective neck dissection for clinically and radiologically
      negative neck disease in early tumors (T1 and T2).

PMID- 22371347
TI  - Malpractice in head and neck surgery: a review of cases.
AB  - OBJECTIVE: To examine the sources of litigation related to the practice of head
      and neck surgery. STUDY DESIGN: Analysis of malpractice claims directly related
      to the diagnosis and treatment of head and neck disease provided by 16 medical
      liability insurance companies. SETTING: Not applicable. SUBJECTS AND METHODS:
      Data were obtained from 16 members of the Physician Insurers Association of
      America. All claims were either filed or closed between 1978 and 2007. Claims
      were evaluated for patient age, the cause for the claim, any surgical
      complications, and indemnity paid. RESULTS: Three hundred fifteen claims were
      identified between 1978 and 2007. The mean patient age was 48 years (median, 47
      years). The greatest number of claims came from the 36- to 45-years age group (n
      = 68, 24.6%). Perioperative complications represented the largest cause of claims
      (n = 169, 53.7%), followed by delay of or missed diagnosis (n = 109, 34.6%) and
      persistence or recurrence of disease (n = 21, 6.7%). Among perioperative
      complications, nerve injuries were the largest group (n = 64, 20.3%), followed by
      airway-related claims (n = 27, 8.6%), esophageal injuries (n = 14, 4.4%), poor
      cosmetic results (n = 14, 4.4%), vessel injuries (n = 11, 3.5%), and
      postoperative infections (n = 2, 0.6%). Overall, mortalities resulted in 62
      (19.7%) claims. CONCLUSIONS: Four important risks for malpractice litigation in
      head and neck surgery were identified: young patient age, perioperative
      complications, delay of or missed diagnosis, and persistence or recurrence of
      disease.

PMID- 22371348
TI  - Extended osteocartilaginous spreader graft for reconstruction of deviated nose.
AB  - OBJECTIVE: Correction of a deviated nose is a challenging problem for which
      different approaches may be considered. This study was designed to introduce a
      new technique for correction of a deviated nose with a high success rate. STUDY
      DESIGN: The study was a prospective follow-up of 59 patients with deviated nose
      who had undergone corrective surgery. SETTING: An extended osteocartilaginous
      spreader graft was harvested from the quadrangular septum and the perpendicular
      plate of the ethmoid. After a medial osteotomy that was performed on the concave
      side, the nasal bone was lateralized and an extended osteocartilaginous spreader
      graft was inserted between the nasal bone and the septum to prevent further
      retraction of the concave side due to fibrotic scar tissue. On the contralateral
      side, a low lateral osteotomy was done as routine. SUBJECTS AND METHODS: The
      operation was done on the 59 cases with deviated nose. The subjects were followed
      up during a period of 8 months to 4 years. According to physical examination,
      postoperative photography, and patients' satisfaction, the final results were
      categorized as excellent, fair, or poor. RESULTS: Forty-eight patients (81.3%)
      were categorized as having excellent results. Eight patients (13.6%) showed fair
      improvement, while the results of surgery in only 3 patients (5.1%) were
      classified as poor. CONCLUSION: An extended osteocartilaginous spreader graft,
      with medial osteotomy and lateralization of the nasal bone on the concave side,
      is a new technique with a high success rate for correction of deviated nose.

PMID- 22371349
TI  - Autophagy prior to chondrocyte cell death during the degeneration of Meckel's
      cartilage.
AB  - The central portion of Meckel's cartilage degenerates almost immediately after
      birth. Whether autophagy is involved in this process remains unclear. Thus, to
      explore the role of autophagy during this process, we have detected the
      expression of autophagy and apoptosis-related markers in embryonic mice. In E15,
      Beclin1 and LC3 expressions were weak and negative in Meckel's cartilage,
      respectively. In E16, chondrocytes of the central portion became hypertrophic.
      Moderate immunoreactivities of Beclin1 and LC3 were observed in prehypertrophic
      and hypertrophic chondrocytes of the central portion. In E17, the degradation
      occurred in the central portion and expanded anteriorly and posteriorly. Beclin1
      expression was observed in Meckel's cartilage with an increase in the
      hypertrophic chondrocytes of the central portion. The expression of LC3 was
      detected specifically in terminally differentiated hypertrophic chondrocytes. The
      mRNA expressions of LC3 and Beclin1 from E15 to E17 significantly increased. This
      result is in accord with the histologic findings. Terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay and
      Caspase 3 expression demonstrated that apoptosis was detected in the lateral part
      of terminal hypertrophic chondrocytes along the degeneration area of Meckel's
      cartilage. In addition, Bcl2 expression increased significantly from E15 to E17.
      These results indicate that autophagy is involved in hypertrophic chondrocytes
      during the degradation of Meckel's cartilage and occurs prior to chondrocyte cell
      death during this process.

PMID- 22371351
TI  - Direct stimulation of the autonomic nervous system modulates activity of the
      brain at rest and when engaged in a cognitive task.
AB  - The effect of autonomic perturbation (AP) on the central nervous system
      functioning is still largely unknown. Using an automated neck suction device to
      stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic
      pathway), operated synchronously with functional magnetic resonance imaging
      (fMRI) acquisition, we investigated the effects of AP on the activity of the
      brain at rest and when engaged in a visuo-spatial attention task. ECG was always
      recorded to index changes in autonomic function. At rest, AP induced increased
      activation in the insula and in the amygdala, which have been previously
      associated with the autonomic control and emotion processing, as well as in the
      caudate nucleus and in the medial temporal cortex, both implicated in cognitive
      functions. Despite a preserved performance during visuo-spatial attention task,
      AP induced increased reaction times and a positive modulation on the activation
      of the right posterior parietal cortex, the occipital cortex, the periaquiductal
      gray, and nuclei of the brainstem. We speculate that this modulation of brain
      activity represents, at different anatomical levels, a compensation mechanism to
      maintain cognitive efficiency under parasympathetic stimulation, which is
      traditionally considered as the system for energy regain and storage. In
      conclusion, this study provides the first evidence of a dynamic interaction
      between AP and higher level functions in humans.

PMID- 22371350
TI  - Perinatal mortality and adverse pregnancy outcomes in a low-income rural
      population of women who smoke.
AB  - We describe adverse pregnancy outcomes, including congenital anomalies, fetal,
      neonatal, and infant mortality among a Missouri population of low-income, rural
      mothers who participated in two randomized smoking cessation trials. In the Baby
      BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650
      women's pregnancy outcomes known (93.5% retention rate). Following the BB trial,
      298 women who had a live infant after November 2004 were recruited again into and
      completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the
      population and perinatal and postneonatal mortality rates were calculated. Of the
      adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than
      20 weeks' gestation, 23% were premature births, and 49% were identified birth
      defects. The perinatal mortality rate was 15.9 per 1000 births (BB study)
      compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births
      (United States). The postneonatal infant mortality rate was 13.4 per 1000 live
      births (BBK) compared with 2.1 per 1000 live births (United States). The health
      disparity in this population of impoverished, rural, pregnant women who smoke,
      particularly in regard to perinatal and infant deaths, warrants attention.

PMID- 22371352
TI  - Total alkaloids of Sophorea alopecuroides-induced down-regulation of AcrAB-TolC
      efflux pump reverses susceptibility to ciprofloxacin in clinical multidrug
      resistant Escherichia coli isolates.
AB  - In this report, total alkaloids extracted from the seeds of Sophorea
      alopecuroides (TASA) was evaluated against clinical Escherichia coli isolates
      resistant to four tested antibiotics, ampicillin (AM), amikacin (AN), cefotaxime
      (CTX) and ciprofloxacin (CIP). The TASA showed an antibacterial activity against
      the multidrug resistant (MDR) isolates. In combination with TASA, synergistic
      effects on the tested antibiotics against the MRD isolates were observed.
      Similarly, the isolates pretreated with a lower dose of TASA yielded increased
      and stable susceptibilities to CIP by 16-32-fold determined by a microbroth
      dilution checkerboard method. Moreover, quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) analysis revealed a constitutive
      overexpression of the AcrAB-TolC pump system in the tested MDR isolates. The
      pretreatment of MDR isolates with TASA resulted in a statistically down-regulated
      expression of acrA and acrB genes, and an up-regulated expression of acrR gene (p
      < 0.05). But the expression of tolC gene was not significantly altered (p >
      0.05). These results suggested that the TASA-induced reversal resistance to CIP
      might be partially through a mechanism of inhibition of the AcrAB-TolC pump
      activity in these isolates, implying that the TASA can be used as a potential
      natural source to develop efflux pump inhibitors (EPI) against AcrAB-TolC pump
      mediated MDR in E. coli isolates.

PMID- 22371353
TI  - The implications of value conflict: how disagreement on values affects self
      involvement and perceived common ground.
AB  - This article presents two studies demonstrating the implications of having
      different values (vs. interests) in a situation where people take opposite
      positions. Study 1 examined how people respond to a range of conflict issues that
      were framed either as referring to conflicting values or as referring to
      conflicting interests. Study 2 used a more immersive methodology, in which
      participants were led to consider either their values or interests in taking up a
      particular position, after which they were presented with a confederate who took
      up the opposite position. Results of both studies converge to demonstrate that
      framing a particular conflict issue in terms of values causes people to
      experience more self-involvement and to perceive less common ground. This result
      can be seen as a potential explanation of why value conflicts tend to escalate
      more easily than conflicts of interests and also offers scope for interventions
      directed at value conflict resolution.

PMID- 22371354
TI  - Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal
      agenesis.
AB  - BACKGROUND: Neural tube defects (NTDs), including anencephaly and spina bifida,
      have a complex etiology. Defects in the planar cell polarity (PCP) signaling
      pathway have been strongly associated with NTDs in animal models and human
      cohorts. In this genetic study, we examined the core PCP gene CELSR1 in NTDs and
      caudal agenesis cases to determine whether mutations at this gene predispose to
      these defects. METHODS: We sequenced the coding region and the exon-intron
      junctions of CELSR1 in a cohort of 473 patients affected with various forms of
      open and closed NTDs (412) or caudal agenesis (61). Novel and rare variants (<1%)
      were genotyped in a cohort of 639 ethnically-matched individuals. The effect of
      novel missense mutations absent in controls and in public databases on protein
      function was predicted in silico. RESULTS: We identified in our cohort one
      nonsense mutation in exon 1 of CELSR1 that truncates the majority of the protein
      in one patient with NTD and one in-frame 12 bp deletion that removes a putative
      PKC phosphorylation "SSR" motif in one caudal agenesis patient. We also detected
      a total of 13 novel missense variants in 12 patients (11 NTDs and 1 caudal
      agenesis) that were predicted to be pathogenic in silico. CONCLUSIONS: We
      detected novel CELSR1 mutations predicted to be pathogenic in 2.9% of our NTD
      cohort and 3.3% of our caudal agenesis cohort. Our findings implicate CELSR1 as a
      risk factor for NTDs or caudal agenesis and provide additional evidence for a
      pathogenic role of PCP signaling in these malformations.

PMID- 22371355
TI  - Probing principles of large-scale object representation: category preference and
      location encoding.
AB  - Knowledge about the principles that govern large-scale neural representations of
      objects is central to a systematic understanding of object recognition. We used
      functional magnetic resonance imaging (fMRI) and multivariate pattern
      classification to investigate two such candidate principles: category preference
      and location encoding. The former designates the preferential activation of
      distinct cortical regions by a specific category of objects. The latter refers to
      information about where in the visual field a particular object is located.
      Participants viewed exemplars of three object categories (faces, bodies, and
      scenes) that were presented left or right of fixation. The analysis of fMRI
      activation patterns revealed the following. Category-selective regions retained
      their preference to the same categories in a manner tolerant to changes in object
      location. However, category preference was not absolute: category-selective
      regions also contained location-tolerant information about nonpreferred
      categories. Furthermore, location information was present throughout high-level
      ventral visual cortex and was distributed systematically across the cortical
      surface. We found more location information in lateral-occipital cortex than in
      ventral-temporal cortex. Our results provide a systematic account of the extent
      to which the principles of category preference and location encoding determine
      the representation of objects in the high-level ventral visual cortex.

PMID- 22371356
TI  - Prehypertension: to treat or not to treat should no longer be the question.

PMID- 22371358
TI  - How to assess the link between vascular biology and arterial hemodynamics?

PMID- 22371357
TI  - Circulating vascular growth factors and central hemodynamic load in the
      community.
AB  - Mean and pulsatile components of hemodynamic load are related to cardiovascular
      disease. Vascular growth factors play a fundamental role in vascular remodeling.
      The links between growth factors and hemodynamic load components are not well
      described. In 3496 participants from the Framingham Heart Study third generation
      cohort (mean age: 40+/-9 years; 52% women), we related 4 tonometry-derived
      measures of central arterial load (carotid femoral pulse wave velocity and
      forward pressure wave, mean arterial pressure, and the global reflection
      coefficient) to circulating concentrations of angiopoietin 2, its soluble
      receptor; vascular endothelial growth factor, its soluble receptor; hepatocyte
      growth factor; insulin-like growth factor 1; and its binding protein 3. Using
      multivariable linear regression models, adjusted for standard cardiovascular risk
      factors, serum insulin-like growth factor 1 concentrations were negatively
      associated with carotid femoral pulse wave velocity, mean arterial pressure, and
      reflection coefficient (P<=0.01 for all), whereas serum vascular endothelial
      growth factor levels were positively associated with carotid femoral pulse wave
      velocity and mean arterial pressure (P<0.04). Serum insulin-like growth factor
      binding protein 3 and soluble angiopoietin 2 receptor levels were positively
      related to mean arterial pressure and to forward pressure wave, respectively
      (P<0.05). In our cross-sectional study of a large community-based sample,
      circulating vascular growth factor levels were related to measures of mean and
      pulsatile hemodynamic load in a pattern consistent with the known physiological
      effects of insulin-like growth factor 1 and vascular endothelial growth factor.

PMID- 22371359
TI  - Hypercontrols in genotype-phenotype analysis reveal ancestral haplotypes
      associated with essential hypertension.
AB  - The angiotensinogen gene locus has been associated with essential hypertension in
      most populations analyzed to date. Increased plasma angiotensinogen levels have
      been proposed as an underlying cause of essential hypertension in whites;
      however, differences in the genetic regulation of plasma angiotensinogen levels
      have also been reported for other populations. The aim of this study was to
      analyze the relationship between angiotensinogen gene polymorphisms and
      haplotypes with plasma angiotensinogen levels and the risk of essential
      hypertension in the Mexican population. We genotyped 9 angiotensinogen gene
      polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and
      G12775, were associated with increased risk, and the strongest association was
      found for the C6309 allele (chi(2)=23.9; P=0.0000009), which resulted in an odds
      ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two
      polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with
      increased plasma angiotensinogen levels but did not show association with
      essential hypertension. The haplotypes H1 (chi(2)=8.1; P=0.004) and H5
      (chi(2)=5.1; P=0.02) were associated with essential hypertension. Using
      phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral
      haplotypes. Our results suggest that the positive association between
      angiotensinogen gene polymorphisms and haplotypes with essential hypertension is
      not simply explained by an increase in plasma angiotensinogen concentration.
      Complex interactions between risk alleles suggest that these haplotypes act as
      "superalleles."

PMID- 22371361
TI  - Hypertension: update 2012.

PMID- 22371360
TI  - Angiotensin II-dependent hypertension requires cyclooxygenase 1-derived
      prostaglandin E2 and EP1 receptor signaling in the subfornical organ of the
      brain.
AB  - Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood
      pressure (BP) regulation. Recently prostaglandin E(2) (PGE(2)) and its receptor
      EP(1) (EP(1)R) have emerged as key players in angiotensin II (Ang II)-dependent
      hypertension (HTN) and related end-organ damage. However, the enzymatic source of
      PGE(2,) that is, COX-1 or COX-2, and its site(s) of action are not known. The
      subfornical organ (SFO) is a key forebrain region that mediates systemic Ang II
      dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that
      cross-talk between PGE(2)/EP(1)R and ROS signaling in the SFO is required for Ang
      II HTN. Radiotelemetric assessment of blood pressure revealed that HTN induced by
      infusion of systemic "slow-pressor" doses of Ang II was abolished in mice with
      null mutations in EP(1)R or COX-1 but not COX-2. Slow-pressor Ang II-evoked HTN
      and ROS formation in the SFO were prevented when the EP(1)R antagonist SC-51089
      was infused directly into brains of wild-type mice, and Ang-II-induced ROS
      production was blunted in cells dissociated from SFO of EP(1)R(-/-) and COX-1(-/
      ) but not COX-2(-/-) mice. In addition, slow-pressor Ang II infusion caused a ~3
      fold increase in PGE(2) levels in the SFO but not in other brain regions.
      Finally, genetic reconstitution of EP(1)R selectively in the SFO of EP(1)R-null
      mice was sufficient to rescue slow-pressor Ang II-elicited HTN and ROS formation
      in the SFO of this model. Thus, COX 1-derived PGE(2) signaling through EP(1)R in
      the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang
      II and suggests that EP(1)R in the SFO may provide a novel target for
      antihypertensive therapy.

PMID- 22371362
TI  - Sarcoplasmic reticulum Ca2+ permeation explored from the lumen side in mdx muscle
      fibers under voltage control.
AB  - Under resting conditions, external Ca(2+) is known to enter skeletal muscle
      cells, whereas Ca(2+) stored in the sarcoplasmic reticulum (SR) leaks into the
      cytosol. The nature of the pathways involved in the sarcolemmal Ca(2+) entry and
      in the SR Ca(2+) leak is still a matter of debate, but several lines of evidence
      suggest that these Ca(2+) fluxes are up-regulated in Duchenne muscular dystrophy.
      We investigated here SR calcium permeation at resting potential and in response
      to depolarization in voltage-controlled skeletal muscle fibers from control and
      mdx mice, the mouse model of Duchenne muscular dystrophy. Using the cytosolic
      Ca(2+) dye Fura2, we first demonstrated that the rate of Ca(2+) increase in
      response to cyclopiazonic acid (CPA)-induced inhibition of SR Ca(2+)-ATPases at
      resting potential was significantly higher in mdx fibers, which suggests an
      elevated SR Ca(2+) leak. However, removal of external Ca(2+) reduced the rate of
      CPA-induced Ca(2+) increase in mdx and increased it in control fibers, which
      indicates an up-regulation of sarcolemmal Ca(2+) influx in mdx fibers. Fibers
      were then loaded with the low-affinity Ca(2+) dye Fluo5N-AM to measure
      intraluminal SR Ca(2+) changes. Trains of action potentials, chloro-m-cresol, and
      depolarization pulses evoked transient Fluo5N fluorescence decreases, and
      recovery of voltage-induced Fluo5N fluorescence changes were inhibited by CPA,
      demonstrating that Fluo5N actually reports intraluminal SR Ca(2+) changes.
      Voltage dependence and magnitude of depolarization-induced SR Ca(2+) depletion
      were found to be unchanged in mdx fibers, but the rate of the recovery phase that
      followed depletion was found to be faster, indicating a higher SR Ca(2+) reuptake
      activity in mdx fibers. Overall, CPA-induced SR Ca(2+) leak at -80 mV was found
      to be significantly higher in mdx fibers and was potentiated by removal of
      external Ca(2+) in control fibers. The elevated passive SR Ca(2+) leak may
      contribute to alteration of Ca(2+) homeostasis in mdx muscle.

PMID- 22371363
TI  - Molecular and biophysical basis of glutamate and trace metal modulation of
      voltage-gated Ca(v)2.3 calcium channels.
AB  - Here, we describe a new mechanism by which glutamate (Glu) and trace metals
      reciprocally modulate activity of the Ca(v)2.3 channel by profoundly shifting its
      voltage-dependent gating. We show that zinc and copper, at physiologically
      relevant concentrations, occupy an extracellular binding site on the surface of
      Ca(v)2.3 and hold the threshold for activation of these channels in a depolarized
      voltage range. Abolishing this binding by chelation or the substitution of key
      amino acid residues in IS1-IS2 (H111) and IS2-IS3 (H179 and H183) loops
      potentiates Ca(v)2.3 by shifting the voltage dependence of activation toward more
      negative membrane potentials. We demonstrate that copper regulates the voltage
      dependence of Ca(v)2.3 by affecting gating charge movements. Thus, in the
      presence of copper, gating charges transition into the "ON" position slower,
      delaying activation and reducing the voltage sensitivity of the channel. Overall,
      our results suggest a new mechanism by which Glu and trace metals transiently
      modulate voltage-dependent gating of Ca(v)2.3, potentially affecting synaptic
      transmission and plasticity in the brain.

PMID- 22371364
TI  - Selectivity filter gating in large-conductance Ca(2+)-activated K+ channels.
AB  - Membrane voltage controls the passage of ions through voltage-gated K (K(v))
      channels, and many studies have demonstrated that this is accomplished by a
      physical gate located at the cytoplasmic end of the pore. Critical to this
      determination were the findings that quaternary ammonium ions and certain
      peptides have access to their internal pore-blocking sites only when the channel
      gates are open, and that large blocking ions interfere with channel closing.
      Although an intracellular location for the physical gate of K(v) channels is well
      established, it is not clear if such a cytoplasmic gate exists in all K(+)
      channels. Some studies on large-conductance, voltage- and Ca(2+)-activated K(+)
      (BK) channels suggest a cytoplasmic location for the gate, but other findings
      question this conclusion and, instead, support the concept that BK channels are
      gated by the pore selectivity filter. If the BK channel is gated by the
      selectivity filter, the interactions between the blocking ions and channel gating
      should be influenced by the permeant ion. Thus, we tested tetrabutyl ammonium
      (TBA) and the Shaker "ball" peptide (BP) on BK channels with either K(+) or Rb(+)
      as the permeant ion. When tested in K(+) solutions, both TBA and the BP acted as
      open-channel blockers of BK channels, and the BP interfered with channel closing.
      In contrast, when Rb(+) replaced K(+) as the permeant ion, TBA and the BP blocked
      both closed and open BK channels, and the BP no longer interfered with channel
      closing. We also tested the cytoplasmically gated Shaker K channels and found the
      opposite behavior: the interactions of TBA and the BP with these K(v) channels
      were independent of the permeant ion. Our results add significantly to the
      evidence against a cytoplasmic gate in BK channels and represent a positive test
      for selectivity filter gating.

PMID- 22371365
TI  - Revisiting inward rectification: K ions permeate through Kir2.1 channels during
      high-affinity block by spermidine.
AB  - Outward currents through Kir2.1 channels play crucial roles in controlling the
      electrical properties of excitable cells, and such currents are subjected to
      voltage-dependent block by intracellular Mg(2+) and polyamines that bind to both
      high- and low-affinity sites on the channels. Under physiological conditions,
      high-affinity block is saturated and yet outward Kir2.1 currents can still occur,
      implying that high-affinity polyamine block cannot completely eliminate outward
      Kir2.1 currents. However, the underlying molecular mechanism remains unknown.
      Here, we show that high-affinity spermidine block, rather than completely
      occluding the single-channel pore, induces a subconducting state in which
      conductance is 20% that of the fully open channel. In a D172N mutant lacking the
      high-affinity polyamine-binding site, spermidine does not induce such a substate.
      However, the kinetics for the transitions between the substate and zero-current
      state in wild-type channels is the same as that of low-affinity block in the
      D172N mutant, supporting the notion that these are identical molecular events.
      Thus, the residual outward current after high-affinity spermidine block is
      susceptible to low-affinity block, which determines the final amplitude of the
      outward current. This study provides a detailed insight into the mechanism
      underlying the emergence of outward Kir2.1 currents regulated by inward
      rectification attributed to high- and low-affinity polyamine blocks.

PMID- 22371366
TI  - Concentration dependent effect of (-)-Epicatechin on Na(+) /K(+) -ATPase and
      Ca(2+) -ATPase inhibition induced by free radicals in hypertensive patients:
      comparison with L-ascorbic acid.
AB  - Although the antioxidant properties of flavonoids are well documented, it is
      still unclear whether these effects are dependent on radical scavenging or iron
      chelating activities. Oxidative stress, a state of excessive reactive oxygen
      species (ROS) activity, is associated with vascular disease conditions such as
      hypertension. Both the anti- and pro-oxidant effects of tea catechins have been
      implicated in the alterations of cellular functions that determine their
      chemoprotective and therapeutic potentials in health and diseases. The present
      study examined the concentration dependent (10(-7) to 10(-4)  m) effects of (-)
      epicatechin and L-ascorbic acid on Na(+) /K(+) -ATPase and Ca(2+) -ATPase
      activity in hypertensive patients and normal subjects. L-ascorbic acid has been
      used as a positive control to compare the effect of (-)-epicatechin. A
      significant (p < 0.0001) decrease in the activities of Na(+) /K(+) -ATPase and
      Ca(2+) -ATPase was observed in hypertensive patients compared with normal
      subjects. We report that (-)-epicatechin shows a significant (p < 0.001) dose
      dependent protective effect against oxidative stress induced by tert-butyl
      hydroperoxide (t-BHP), which is manisfested as a decrease in the activity of
      erythrocyte Na(+) /K(+) -ATPase and Ca(2+) -ATPase, in hypertensive patients as
      well as normal subjects. The effect of L-ascorbic acid was also significant (p <
      0.001) and was comparable with that of (-)-epicatechin.

PMID- 22371367
TI  - Predicting vocal emotion expressions from the human brain.
AB  - Speech is an important carrier of emotional information. However, little is known
      about how different vocal emotion expressions are recognized in a receiver's
      brain. We used multivariate pattern analysis of functional magnetic resonance
      imaging data to investigate to which degree distinct vocal emotion expressions
      are represented in the receiver's local brain activity patterns. Specific vocal
      emotion expressions are encoded in a right fronto-operculo-temporal network
      involving temporal regions known to subserve suprasegmental acoustic processes
      and a fronto-opercular region known to support emotional evaluation, and,
      moreover, in left temporo-cerebellar regions covering sequential processes. The
      right inferior frontal region, in particular, was found to differentiate distinct
      emotional expressions. The present analysis reveals vocal emotion to be encoded
      in a shared cortical network reflected by distinct brain activity patterns. These
      results shed new light on theoretical and empirical controversies about the
      perception of distinct vocal emotion expressions at the level of large-scale
      human brain signals.

PMID- 22371368
TI  - Laparoscopic management of large ovarian cysts.
AB  - The aim of this study was to describe a new technique for laparoscopic removal of
      large ovarian cystic masses. The authors performed a retrospective study during
      the period January 2008 to December 2009 in the Second Department of Obstetrics
      and Gynecology of Aretaieion University Hospital; 19 women with large ovarian
      cysts were included in the study. During the study period, 53 women underwent
      laparoscopic excision of ovarian cysts. Among them, 19 had very large complex
      ovarian cysts with a mean diameter of 8.4 cm. The mean age of the patients was
      32.1 years. Ultrasound examination revealed findings suggestive of benign disease
      in all patients. In 8 out of 19 patients CA-125 levels were elevated, ranging
      from 40.5 to 194.7 IU/mL. A 5-mm suprapubic trocar was directly inserted into the
      cyst and fluid contents aspirated, so the decompressed cyst could fit in a 5-cm
      laparoscopic bag. The cyst wall was carefully detached from the healthy ovarian
      tissue and placed in the bag without any spillage. The remaining cyst wall was
      removed from the peritoneal cavity with the laparoscopic bag. The mean operative
      time was 45 minutes. No operative or postoperative complications were noted.
      There was no conversion to laparotomy. Mean hospital stay was 1 day. Pathology
      revealed 7 endometriomas, 3 mucinous cystadenomas, 3 serous cystadenomas, 3
      serous cysts, and 3 teratomas. Direct trocar insertion within the ovarian cyst
      followed by aspiration of the fluid contents is a safe and feasible method for
      the laparoscopic management of large ovarian cysts.

PMID- 22371369
TI  - Meta-analysis: multidisciplinary fall prevention strategies in the acute care
      inpatient population.
AB  - BACKGROUND: Inpatient falls are common adverse events that lead to inpatient
      injury, increased length of stay, healthcare costs, litigation, and are a focus
      of patient safety and healthcare quality. Fall prevention methods are currently
      evolving to address the problem. PURPOSE: To examine the available data
      evaluating multidisciplinary fall prevention strategies in the acute inpatient
      setting. DATA SOURCES: A complete literature search of MEDLINE, CINAHL, EMBASE
      and the Cochrane Library through December 2011 was used. The bibliographies of
      all systematic reviews and meta-analyses were hand searched. STUDY SELECTION:
      Only primary research studies relating to acute care inpatient hospital
      multidisciplinary fall prevention were included. Selected papers were assessed
      for quality by 2 authors using a 20-point scale previously used in the fall
      literature. DATA EXTRACTION: Each selected study was carefully hand searched by 2
      authors for the purposes of data extraction. Study results, in fall rate per 1000
      patient days, and the characteristics of the interventions used were extracted
      for analysis. DATA SYNTHESIS: Effect sizes (odds ratios) and 95% confidence
      intervals were derived for individual studies and then combined across research
      reports using a random-effects meta-analysis. CONCLUSIONS: Fall prevention
      strategies have a significant but small effect on fall rates despite the use of
      complex, multidisciplinary interventions. Additional randomized trials are needed
      to examine the possible benefits of multidisciplinary fall prevention strategies
      in the acute inpatient setting.

PMID- 22371370
TI  - Dissecting the "CHF admission": an evidence-based review of the evaluation and
      management of acute decompensated heart failure for the hospitalist.
AB  - Acute decompensated heart failure (ADHF) is one of the most common conditions
      managed by hospitalists. Here we review the most recent evidence applicable to
      hospitalists for the diagnosis, risk stratification, and management of patients
      presenting with ADHF. By following a structured approach based on the patient's
      symptoms, history, physical examination, and laboratory testing, the clinician
      can make the diagnosis of heart failure efficiently. Because patients exhibit a
      wide spectrum of risk for adverse outcomes, both in the hospital and after
      discharge, assessing for clinical factors associated with these outcomes is
      essential. Congestion should be managed primarily with diuretics, and
      vasodilators may be helpful in certain patients. Given high rates of readmission,
      hospitalists should ensure that patients received evidence-based therapy, heart
      failure education is performed, and follow-up is in place before discharge.

PMID- 22371371
TI  - The heat shock response: systems biology of proteotoxic stress in aging and
      disease.
AB  - All organisms sense and respond to environmental and physiological stress by
      inducing cell stress responses that protect core biosynthetic processes such as
      DNA repair, protein folding, and clearance of damaged proteins. Of these, the
      heat shock response (HSR) protects the proteome against acute exposure to
      elevated temperatures, oxidants, and heavy metals, for example, and to the
      chronic expression of metastable, aggregation-prone proteins associated with
      aging and diseases of protein conformation. Induction of the HSR leads to the
      rapid and robust expression of molecular chaperones and other cell-protective
      pathways to protect nascent chain synthesis and folding, to prevent misfolding
      and aggregation, and to promote recovery from stress-induced damage. This review
      examines the properties of the stress-responsive transcription factor, HSF-1, in
      the regulation of the HSR, our current understanding of the stress-sensing
      mechanisms that recognize and distinguish between acute stress such as heat shock
      and chronic proteostasis imbalance as occurs in neurodegenerative diseases, and
      the cell nonautonomous control of the HSR by neuronal signaling in metazoans.
      This complex, systems-wide interdependence ensures cellular health span and
      organismal life span.

PMID- 22371372
TI  - Nutrient-dependent acetylation controls basic regulatory metabolic switches and
      cellular reprogramming.
AB  - Organisms must be able to selectively tailor their ability to use the
      macronutrients of carbohydrate, protein, and fat based on their availability. In
      different cell types, how the nutrient fluctuations are sensed and the mechanisms
      by which the pathways of central metabolism are switched to favor the use of one
      particular nutrient type over another are topics of intense interest. Protein
      acetylation is one major evolutionary conserved mechanism by which nutrient
      fluctuations are sensed within cells and subsequently coupled with metabolic
      switching. In this review, we present the case of PGC-1alpha acetylation and how
      the control of PGC-1alpha's activity by acetylation sets into motion a wide range
      of metabolic adaptations that makes this protein an exemplary model for
      acetylation-mediated mechanisms of nutrient sensing and communication.

PMID- 22371373
TI  - LitR of Vibrio salmonicida is a salinity-sensitive quorum-sensing regulator of
      phenotypes involved in host interactions and virulence.
AB  - Vibrio (Aliivibrio) salmonicida is the causal agent of cold-water vibriosis, a
      fatal bacterial septicemia primarily of farmed salmonid fish. The molecular
      mechanisms of invasion, colonization, and growth of V. salmonicida in the host
      are still largely unknown, and few virulence factors have been identified. Quorum
      sensing (QS) is a cell-to-cell communication system known to regulate virulence
      and other activities in several bacterial species. The genome of V. salmonicida
      LFI1238 encodes products presumably involved in several QS systems. In this
      study, the gene encoding LitR, a homolog of the master regulator of QS in V.
      fischeri, was deleted. Compared to the parental strain, the litR mutant showed
      increased motility, adhesion, cell-to-cell aggregation, and biofilm formation.
      Furthermore, the litR mutant produced less cryptic bioluminescence, whereas
      production of acylhomoserine lactones was unaffected. Our results also indicate a
      salinity-sensitive regulation of LitR. Finally, reduced mortality was observed in
      Atlantic salmon infected with the litR mutant, implying that the fish were more
      susceptible to infection with the wild type than with the mutant strain. We
      hypothesize that LitR inhibits biofilm formation and favors planktonic growth,
      with the latter being more adapted for pathogenesis in the fish host.

PMID- 22371374
TI  - Afa/Dr diffusely adhering Escherichia coli strain C1845 induces neutrophil
      extracellular traps that kill bacteria and damage human enterocyte-like cells.
AB  - We recently documented the neutrophil response to enterovirulent diffusely
      adherent Escherichia coli expressing Afa/Dr fimbriae (Afa/Dr DAEC), using the
      human myeloid cell line PLB-985 differentiated into fully mature neutrophils.
      Upon activation, particularly during infections, neutrophils release neutrophil
      extracellular traps (NETs), composed of a nuclear DNA backbone associated with
      antimicrobial peptides, histones, and proteases, which entrap and kill pathogens.
      Here, using fluorescence microscopy and field emission scanning electron
      microscopy, we observed NET production by PLB-985 cells infected with the Afa/Dr
      wild-type (WT) E. coli strain C1845. We found that these NETs were able to
      capture, immobilize, and kill WT C1845 bacteria. We also developed a coculture
      model of human enterocyte-like Caco-2/TC7 cells and PLB-985 cells previously
      treated with WT C1845 and found, for the first time, that the F-actin
      cytoskeleton of enterocyte-like cells is damaged in the presence of bacterium
      induced NETs and that this deleterious effect is prevented by inhibition of
      protease release. These findings provide new insights into the neutrophil
      response to bacterial infection via the production of bactericidal NETs and
      suggest that NETs may damage the intestinal epithelium, particularly in
      situations such as inflammatory bowel diseases.

PMID- 22371375
TI  - Timing of Toll-like receptor 9 agonist administration in pneumococcal vaccination
      impacts both humoral and cellular immune responses as well as nasopharyngeal
      colonization in mice.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs, CpG
      ODN, are Toll-like receptor 9 agonists (TLR9a), which have been used as adjuvants
      in pneumococcal vaccines to improve antibody responses in immunodeficient
      patients. Here, we examined whether the coadministration of TLR9a with
      pneumococcal CRM(197)-conjugate vaccine enhances protection against pneumococcal
      colonization, the levels of antipolysaccharide antibodies, and the CD4(+) T-cell
      responses. Wild-type BALB/c mice and B-cell-deficient BALB/c Igh-J(tm1Dhu) mice
      were immunized twice with the following: (i) PCV alone; (ii) simultaneous PCV and
      TLR9a; (iii) PCV and then TLR9a, after a 48-h delay; (iv) TLR9a alone; and (v)
      phosphate-buffered saline. Nasopharyngeal protection, serum antibodies, CD4(+) T
      cell responses, and clearance of bacteremia after intraperitoneal challenge with
      Streptococcus pneumoniae 6B were evaluated. We found decreased nasopharyngeal
      protection against S. pneumoniae 6B colonization after simultaneous immunization
      with PCV and TLR9a compared to immunization with PCV alone in wild-type BALB/c
      mice (P = 0.037). A similar trend was observed in B-cell-deficient BALB/c Igh
      J(tm1Dhu) mice. Simultaneous administration did not enhance antibody levels and
      lowered the CRM(197)-specific cytokine release of gamma interferon, interleukin-2
      (IL-2), IL-5 and IL-13. Immunization with PCV and then TLR9a, after a 48-h delay,
      significantly improved nasopharyngeal protection compared to simultaneous
      administration (P = 0.011). Furthermore, delaying TLR9a delivery increased
      antibody titers compared to both simultaneous administration (P = 0.001) and PCV
      immunization alone (P = 0.026). In conclusion, the immunological and clinical
      impact of adjuvanting a pneumococcal conjugate vaccine (Prevnar; Pfizer) with a
      TLR9a is highly depended on timing of the adjuvant administration. Thus, careful
      timing of adjuvant administration may improve novel vaccine formulations.

PMID- 22371376
TI  - Vitamin B12-mediated restoration of defective anaerobic growth leads to reduced
      biofilm formation in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa undergoes cell elongation and forms robust biofilms during
      anaerobic respiratory growth using nitrate (NO(3)(-)) as an alternative electron
      acceptor. Understanding the mechanism of cell shape change induced upon
      anaerobiosis is crucial to the development of effective treatments against P.
      aeruginosa biofilm infection. Here, we uncovered the molecular basis of
      anaerobiosis-triggered cell elongation and identified vitamin B(12) to be a
      molecule that can reinstate defective anaerobic growth of P. aeruginosa. The
      ratio of total cellular DNA content to protein content was significantly
      decreased in the PAO1 strain grown under anaerobic conditions, indicating that
      DNA replication is impaired during anaerobic growth. Anaerobic growth of PAO1
      reached a higher cell density in the presence of vitamin B(12), an essential
      coenzyme of class II ribonucleotide reductase. In addition, cell morphology
      returned to a normal rod shape and transcription of stress-response genes was
      downregulated under the same anaerobic growth conditions. These results suggest
      that vitamin B(12), the production of which was suppressed during anaerobic
      growth, can restore cellular machineries for DNA replication and therefore
      facilitate better anaerobic growth of P. aeruginosa with normal cell division.
      Importantly, biofilm formation was substantially decreased when grown with
      vitamin B(12), further demonstrating that anaerobiosis-induced cell elongation is
      responsible for robust biofilm formation. Taken together, our data reveal
      mechanistic details of a morphological change that naturally occurs during
      anaerobic growth of P. aeruginosa and illustrates the ability of vitamin B(12) to
      modulate the biofilm-forming capacity of P. aeruginosa under such condition.

PMID- 22371377
TI  - Adjustment of cerebrospinal fluid protein for red blood cells in neonates and
      young infants.
AB  - OBJECTIVE: To determine the relationship between cerebrospinal fluid (CSF) red
      blood cell (RBC) count and CSF protein in neonates and young infants undergoing
      lumbar puncture. DESIGN: Cross-sectional study. SETTING: Urban tertiary care
      children's hospital. PATIENTS: Infants 56 days of age and younger who had a
      lumbar puncture in the emergency department between January 1, 2005 and July 31,
      2009 were eligible for inclusion. Infants with missing laboratory data,
      exceedingly high CSF red blood cell counts, or conditions known to elevate CSF
      protein were excluded. MEASUREMENTS: Linear regression was used to determine the
      association between CSF RBC and CSF protein. RESULTS: Of 1986 infants, 56 days of
      age or younger, who underwent lumbar puncture in the emergency department during
      the study period, 1241 (62.5%) met inclusion criteria. The median age was 34 days
      (interquartile range: 19-46 days); 45% of patients were male. The median CSF RBC
      count was 40 cells/mm(3) (interquartile range: 2-1080 cells/mm(3)); 11.8% of
      patients had a CSF RBC >10,000 cells/mm(3). CSF protein increased by 1.9 mg/dL
      (95% confidence interval: 1.7-2.1 mg/dL) per 1000 CSF RBCs for all included
      patients. Restricting analysis to patients without pleocytosis yielded comparable
      results, as did subanalyses by age and delivery type. CONCLUSIONS: We found that
      CSF protein concentrations increased by approximately 2 mg/dL for every 1000 CSF
      RBCs. These data may assist clinicians in interpreting CSF protein concentrations
      in infants 56 days of age and younger in the context of traumatic lumbar
      punctures.

PMID- 22371378
TI  - Magnetic resonance imaging findings of the mass-forming type of autoimmune
      pancreatitis: comparison with pancreatic adenocarcinoma.
AB  - PURPOSE: To determine the characteristic magnetic resonance imaging (MRI)
      features of mass-forming autoimmune pancreatitis (AIP), which allow its
      differentiation from pancreatic adenocarcinoma (PAC). MATERIALS AND METHODS: MR
      images of 37 patients with either pathologically proven, mass-forming AIPs (n =
      9) or PACs (n = 28) were retrospectively reviewed. The pancreatic MR protocol
      included unenhanced images, contrast-enhanced dynamic images, diffusion-weighted
      imaging (DWI), and MR-cholangiopancreatography (MRCP). Two reviewers analyzed the
      MR images regarding the number, location, morphologic features, and enhancement
      degree and pattern of the lesions as well as secondary changes of the pancreatic
      parenchyma, the biliary and pancreatic ducts. The size and apparent diffusion
      coefficient (ADC) values of the lesions were measured. RESULTS: Although
      sensitivities were low (28.6%-44.4%), specificities of multiplicity, capsule-like
      rim enhancement, and skipped stricture of the biliary or pancreatic duct in mass
      forming AIP were high (100%). Sensitivities and specificities of irregular or
      geographic shape, delayed enhancement, and a low ADC value <1.26 * 10(-3) mm(2)
      /s in mass-forming AIP were favorable (71.4%-83.3% and 78.5%-89.3%). CONCLUSION:
      Although to differentiate mass-forming AIP from pancreatic cancer is difficult,
      the combination of MRI findings including contrast-enhanced dynamic images, MRCP,
      and DWI can be a help.

PMID- 22371379
TI  - Nurse-pharmacist collaboration on medication reconciliation prevents potential
      harm.
AB  - BACKGROUND: Medication reconciliation can prevent some adverse drug events
      (ADEs). Our prospective study explored whether an easily replicable nurse
      pharmacist led medication reconciliation process could efficiently and
      inexpensively prevent potential ADEs. METHODS: Nurses at a 1000 bed urban,
      tertiary care hospital developed the home medication list (HML) through patient
      interview. If a patient was not able to provide a written HML or recall
      medications, the nurses reviewed the electronic record along with other sources.
      The nurses then compared the HML to the patient's active inpatient medications
      and judged whether the discrepancies were intentional or potentially
      unintentional. This was repeated at discharge as well. If the prescriber changed
      the order when contacted about a potential unintentional discrepancy, it was
      categorized as unintentional and rated on a 1-3 potential harm scale. RESULTS:
      The study included 563 patients. HML information gathering averaged 29 minutes.
      Two hundred twenty-five patients (40%; 95% confidence interval [CI], 36%-44%) had
      at least 1 unintended discrepancy on admission or discharge. One hundred sixty
      two of the 225 patients had an unintended discrepancy ranked 2 or 3 on the harm
      scale. It cost $113.64 to find 1 potentially harmful discrepancy. Based on the
      2008 cost of an ADE, preventing 1 discrepancy in every 290 patient encounters
      would offset the intervention costs. We potentially averted 81 ADEs for every 290
      patients. CONCLUSION: Potentially harmful medication discrepancies occurred
      frequently at both admission and discharge. A nurse-pharmacist collaboration
      allowed many discrepancies to be reconciled before causing harm. The
      collaboration was efficient and cost-effective, and the process potentially
      improves patient safety.

PMID- 22371380
TI  - Selective recognition of acetate ion based on fluorescence enhancement
      chemosensor.
AB  - Fluorescence study of the complexation between uranyl salophen (L) and some
      common anions in acetonitrile-water (90:10, v/v) solution showed a tendency of L
      toward acetate ion (AcO-). The fluorescence enhancement of L is attributed to a
      1:1 complex formation between L and acetate ion which was utilized as the basis
      for the selective detection of AcO-. The association constant of the 1:1 complex
      formation of L-AcO- was calculated as 6.60 * 10(6) . The linear response range of
      the fluorescent chemosensor covers a AcO- concentration range of 1.6 * 10(-7) to
      2.5 * 10(-5)  mol/L, with a detection limit of 2.5 * 10(-8)  mol/L. L showed a
      selective and sensitive fluorescence enhancement response toward acetate ion over
      I3- , NO3-, CN-, CO3 (2-), Br-, Cl-, F-, H2 PO4- and SO4 (2-) , which was
      attributed to the higher stability of inorganic complex between acetate and L.

PMID- 22371381
TI  - Clinical utility of apparent diffusion coefficient values obtained using high b
      value when diagnosing prostate cancer using 3 tesla MRI: comparison between ultra
      high b-value (2000 s/mm2) and standard high b-value (1000 s/mm2).
AB  - PURPOSE: To determine whether the apparent diffusion coefficient (ADC) obtained
      using b = 2000 s/mm(2) upon 3 Tesla (T) diffusion-weighted MRI is superior to b =
      1000 s/mm(2) for discriminating malignant from normal prostate tissue and
      predicting the aggressiveness of prostate cancer, using histopathological
      findings of radical prostatectomy as a reference. MATERIALS AND METHODS: Eighty
      prostate cancer patients underwent preoperative 3T MRI including diffusion
      weighted imaging with b-values of 0, 1000, and 2000 s/mm(2) . ADCs were measured
      for malignant lesions and normal sites on three sets of ADC maps calculated with
      monoexponential fitting between b = 0 and 1000, 0 and 2000, and 1000 and 2000,
      respectively. The relationship between the ADC and Gleason score was evaluated.
      RESULTS: The areas under the ROC curves for b = 0,1000, b = 0,2000, and b =
      1000,2000 were 0.896, 0.937, and 0.857, respectively, in the peripheral zone (PZ)
      and 0.877, 0.889, and 0.731, respectively, in the transition zone (TZ). The
      difference between b = 0,1000 and b = 0,2000 was significant in PZ (P = 0.033),
      but not in TZ (P = 0.84). Weak but significant negative correlations were
      identified between ADCs and Gleason score in both PZ and TZ cancer at b = 0,1000
      and b = 0,2000 (r = -0.323 to -0.341). CONCLUSION: For 3T MRI, ADCs using b =
      0,2000 are more accurate than b = 0,1000 for diagnosing PZ cancer, and as
      accurate for TZ cancer.

PMID- 22371382
TI  - Faith and protection: the construction of hope by parents of children with
      leukemia and their oncologists.
AB  - BACKGROUND: Oncologists are criticized for fostering unrealistic hope in patients
      and families, but criticisms reflect a perspective that is oversimplified and
      "expert" guidance that is ambiguous or impractical. Our aim was to understand how
      pediatric oncologists manage parents' hope in practice and to evaluate how they
      address parents' needs. METHODS: Participants were 53 parents and 12 oncologists
      whom they consulted across six U.K. centers. We audio recorded consultations
      approximately 1-2, 6, and 12 months after diagnosis. Parents were interviewed
      after each consultation to elicit their perspectives on the consultation and
      clinical relationship. Transcripts of consultations and interviews were analyzed
      qualitatively. RESULTS: Parents needed hope in order to function effectively in
      the face of despair, and all wanted the oncologists to help them be hopeful. Most
      parents focused hope on the short term. They therefore needed oncologists to be
      authoritative in taking responsibility for the child's long-term survival while
      cushioning parents from information about longer-term uncertainties and being
      positive in providing information about short-term progress. A few parents who
      could not fully trust their oncologist were unable to hope. CONCLUSION:
      Oncologists' pivotal role in sustaining hope was one that parents gave them. Most
      parents' "faith" in the oncologist allowed them to set aside, rather than deny,
      their fears about survival while investing their hopes in short-term milestones.
      Oncologists' behavior generally matched parents' needs, contradicting common
      criticisms of oncologists. Nevertheless, oncologists need to identify and address
      the difficulty that some parents have in fully trusting the oncologist and,
      consequently, being hopeful.

PMID- 22371384
TI  - Pediatric observation status: are we overlooking a growing population in
      children's hospitals?
AB  - BACKGROUND: Inpatient administrative datasets often exclude observation stays, as
      observation is considered to be outpatient care. The extent to which this status
      is applied to pediatric hospitalizations is not known. OBJECTIVE: To characterize
      trends in observation status code utilization and 1-day stays among children
      admitted from the emergency department (ED), and to compare patient
      characteristics and outcomes associated with observation versus inpatient stays.
      DESIGN: Retrospective longitudinal analysis of the 2004-2009 Pediatric Health
      Information System (PHIS). SETTING: Sixteen US freestanding children's hospitals
      contributing outpatient and inpatient data to PHIS. PATIENTS: Admissions to
      observation or inpatient status following ED care in study hospitals.
      MEASUREMENTS: Proportions of observation and 1-day stays among all admissions
      from the ED were calculated each year. Top ranking discharge diagnoses and
      outcomes of observation were determined. Patient characteristics, discharge
      diagnoses, and return visits were compared for observation and 1-day stays.
      RESULTS: The proportion of short-stays (including both observation and 1-day
      stays) increased from 37% to 41% between 2004 and 2009. Since 2007, observation
      stays have outnumbered 1-day stays. In 2009, more than half of admissions from
      the ED for 6 of the top 10 ranking discharge diagnoses were short-stays. Fewer
      than 25% of observation stays converted to inpatient status. Return visits and
      readmissions following observation were no more frequent than following 1-day
      stays. CONCLUSIONS: Children admitted under observation status make up a
      substantial proportion of acute care hospitalizations. Analyses of inpatient
      administrative databases that exclude observation stays likely result in an
      underestimation of hospital resource utilization for children.

PMID- 22371383
TI  - Anthracycline regimen adherence in older patients with early breast cancer.
AB  - BACKGROUND: Rates of anthracycline adherence in breast cancer (BC) patients are
      unknown, but noncompletion of chemotherapy is associated with worse outcomes.
      METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database,
      we obtained demographics, comorbidities, tumor characteristics, and treatment and
      hospitalization data from stage I-III BC patients diagnosed at age >=66 years in
      1996-2005 treated with surgery who had anthracycline claims. We compared
      variables between patients with claims for less than four cycles, considered
      nonadherent cases, and those with claims for four or more cycles using logistic
      regression analyses. RESULTS: The sample included 7,399 patients, of whom 1,222
      (16.5%) were nonadherent cases. Two hundred forty-three (3.3%) patients had one
      claim, 298 (4.0%) had two claims, and 681 (9.2%) had three claims. The
      multivariate regression model showed statistically significant associations
      between nonadherence and older age, black race, unmarried status, diagnosis
      before the year 2001, and hospitalizations. CONCLUSIONS: Eighty-three percent of
      older patients with early-stage BC completed at least four cycles of an
      anthracycline-based chemotherapy regimen. We identified a subset of patients with
      a higher likelihood of not adhering to the course of treatment. Further research
      is warranted to develop interventions to enhance adherence.

PMID- 22371385
TI  - Air embolism complicating computed tomography-guided core needle biopsy of the
      lung.
AB  - Computed tomography-guided transthoracic lung biopsy is a common clinical
      procedure for the diagnosis of a broad range of pulmonary pathological
      conditions. Mild self-limiting pneumothorax and haemoptysis are common
      complications of this procedure. Air embolism is a potentially life-threatening
      but extremely rare complication. We report a case of an air embolism in the left
      ventricle of the heart that developed after a computed tomography-guided
      percutaneous needle biopsy of the lung. The patient did not exhibit cardiac or
      cerebral symptoms after conservative treatment. The patient underwent a
      successful left thoracotomy with a lobectomy of the left lower lobe of the lung 5
      days after the biopsy and recovered uneventfully.

PMID- 22371386
TI  - Pleural lipoma: a non-surgical lesion?
AB  - Pleural lipomas are benign tumours that develop at the expense of adipose
      tissues, and they never evolve towards liposarcoma. Located usually at the
      mediastinal, bronchial and pulmonary levels, a pleural situation is extremely
      rare. Chest X-rays usually detect them and computed tomography scans confirm the
      diagnosis. As complications occur, a wait-and-see policy is common. We report our
      pleural lipoma surgical exeresis experience since 1999. We have operated on five
      cases of pleural lipomas among nearly 1800 cases of thoracic exeresis: three male
      and two female patients, without obesity (in all cases, body mass index (BMI) <
      28). The mean age was 54.6 years (range 35-72 years). Four patients were
      electively operated and one in emergency, three with video-assisted thoracic
      surgery (VATS) procedure and two with open chest surgery, without recurrent
      cases. Advancements in VATS have greatly reduced the morbidity rate of these
      benign tumours especially if exeresis is performed early on a small,
      uncomplicated adhesion-free tumour. On the other hand, the operation may be
      deleterious, complicated by the presence of a large lipoma or in a complicating
      situation. In our opinion, we should revise the wait-and-see policy when facing
      these lesions considering their evolutionary potential. We should advise VATS in
      pleural lipomas.

PMID- 22371387
TI  - Effects of soccer matches on neutrophil and lymphocyte functions in female
      university soccer players.
AB  - In this study, changes in physical fatigue and biological functions of Japanese
      female soccer players were investigated by determining changes in neutrophil and
      lymphocyte functions. Study subjects included 18 female soccer players. Body
      composition, serum myogenic enzymes, neutrophil function, including reactive
      oxygen species (ROS) production capability, phagocytic activity (PA) and serum
      opsonic activity, as well as lymphocyte subpopulation were measured before and
      after a soccer match. Levels of myogenic enzymes (AST, ALT, CK and LDH) and
      immunoglobulins (IgG and IgA) and complements (C3) increased significantly after
      the match. In addition, leukocyte, neutrophils and lymphocyte counts increased
      whereas total PA decreased significantly. The number of T and Th1 cells (subsets
      of T helper cells) decreased whereas Th2 increased significantly. In addition,
      the number of B cells increased and NK cells decreased significantly after the
      match. The match was found to result in degenerative changes in and damage to
      athlete muscle tissues together with damage- and change-mediated stress. These
      data also suggest a post-match accelerated inflammatory reaction and potential
      immunosuppression as indicated by reductions in neutrophil PA and lymphocyte
      functions.

PMID- 22371389
TI  - Longevity of a mixture of acetamiprid and bifenthrin (Transport(TM) ) at the
      termiticidal application rate.
AB  - BACKGROUND: The 30 month longevity, mobility and insecticidal activity of a
      combination of acetamiprid and bifenthrin currently marketed in the United States
      for the prevention of termite infestation in buildings was investigated in
      greenhouse and laboratory studies. RESULTS: Acetamiprid dissipated to below the
      limit of detection within 7 months of application, while bifenthrin remained in
      the soil at levels sufficient to kill termites for the duration of the study.
      Acetamiprid was detected in decreasing amounts in eluates of treated soil from
      months 1 to 4, while no bifenthrin was detected in eluates at any time. The
      treated soil remained toxic to termites for the 30 month duration of the study.
      Two indices of synergy between technical-grade acetamiprid and bifenthrin
      demonstrated that it is unlikely that there would be any synergism between the
      two active ingredients in the field. The presence of vegetation did not have a
      significant effect on the longevity of bifenthrin, except at intermediate times,
      where residues in the treated soil were higher in vegetated plots, depending on
      depth and time. CONCLUSIONS: Acetamiprid has a short residual time in soil, and
      this formulation's effectiveness beyond about 7 months against subterranean
      termites is due to the bifenthrin content.

PMID- 22371388
TI  - Longitudinal assessment of symptom severity among hospitalized elders diagnosed
      with cancer, heart failure, and chronic obstructive pulmonary disease.
AB  - BACKGROUND: Pain, dyspnea, and anxiety are common among patients with cancer,
      heart failure (HF), and chronic obstructive pulmonary disease (COPD), yet little
      is known about the severity of symptoms over time. OBJECTIVE: To determine the
      prevalence, severity, burden, and predictors of symptoms during the course of
      hospitalization and at 2 weeks after discharge. DESIGN: A prospective cohort
      study. SETTING: A large academic university. PATIENTS: Patients were 65 years or
      older with a primary diagnosis of cancer, COPD, or HF. MEASUREMENTS: Daily living
      skills and depression were recorded at enrollment. Symptoms were assessed daily
      and 2 weeks postdischarge. RESULTS: At baseline, most participants reported
      moderate/severe pain (54%), dyspnea (53%), and anxiety (62%). Almost two-thirds
      (64%) had 2 or more symptoms at a moderate/severe level. The prevalence of
      moderate/severe symptoms decreased at the 24-hour assessment (pain = 42%, dyspnea
      = 45%, anxiety = 55%, burden = 55%) and again at follow-up (pain = 28%, dyspnea =
      27%, anxiety = 25%, burden = 30%). While there was no association between primary
      diagnosis and symptom severity at baseline or 24-hour assessment, at 2-week
      follow-up, a higher percentage of patients with COPD had moderate/severe pain
      (54%, chi(2) = 22.0, P = 0.001), dyspnea (45%, chi(2) = 9.3, P = 0.05), and
      overall symptom burden (55%, chi(2) = 25.9, P = 0.001) than those with cancer
      (pain = 22%, dyspnea = 16%, symptom burden = 16%) or HF (pain = 25%, dyspnea =
      24%, symptom burden = 28%). Predictors of symptom burden at follow-up were COPD
      (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 2.0, 27.7) and probable
      depression (OR = 6.1; 95% CI = 2.1, 17.8). CONCLUSION: The majority of inpatients
      with chronic illness reported high severity of symptoms. Symptoms improved over
      time but many patients, particularly those with COPD, had high symptom severity
      at follow-up.

PMID- 22371390
TI  - Spectrophotometric simultaneous determination of orotic acid, creatinine and uric
      acid by orthogonal signal correction-partial least squares in spiked real
      samples.
AB  - An orthogonal signal correction-partial least squares (OSC-PLS) method was
      developed for the simultaneous spectrophotometric determination of orotic acid
      (OA), creatinine (CRE), and uric acid (UA) in spiked real samples. By
      multivariate calibration methods, such as PLS regression, it is possible to
      obtain a model adjusted to the concentration values of the mixtures used in the
      calibration range. The effect of OSC used to remove the information unrelated to
      the target variables is studied. In this study, the calibration model is based on
      absorption spectra in the 220-320 nm rang for 36 different mixtures of OA, CRE
      and UA. Calibration matrices contained 1.74-47.00 of OA, 1.13-33.95 of CRE, and
      1.68-28.58 of UA in ug/ml. The number of principal component for OA, CRE, and UA
      with OSC were 3, 4, and 4, and 4, 6, and 5, without OSC, respectively. The
      evaluation of the prediction errors for the prediction set reveals that the OSC
      treated data give substantially lower root mean square error of prediction
      (RMSEP) values than the original data. The RMSEP for OA, CRE, and UA with OSC
      were 0.69, 0.20, and 0.53 and 0.80, 0.69, and 0.73 without OSC, respectively. The
      proposed method was applied for the simultaneous determination of OA, CRE, and UA
      in spiked biological fluids with satisfactory results.

PMID- 22371391
TI  - Type I IFN drives a distinctive dendritic cell maturation phenotype that allows
      continued class II MHC synthesis and antigen processing.
AB  - Microbial molecules or cytokines can stimulate dendritic cell (DC) maturation,
      which involves DC migration to lymph nodes and enhanced presentation of Ag to
      launch T cell responses. Microbial TLR agonists are the most studied inducers of
      DC maturation, but type I IFN (IFN-I) also promotes DC maturation. In response to
      TLR stimulation, DC maturation involves a burst of Ag processing with enhanced
      expression of peptide-class II MHC complexes and costimulator molecules.
      Subsequently, class II MHC (MHC-II) synthesis and expression in intracellular
      vacuolar compartments is inhibited, decreasing Ag processing function. This
      limits presentation to a cohort of Ags kinetically associated with the maturation
      stimulus and excludes presentation of Ags subsequently experienced by the DC. In
      contrast, our studies show that IFN-I enhances DC expression of MHC-II and
      costimulatory molecules without a concomitant inhibition of subsequent MHC-II
      synthesis and Ag processing. Expression of mRNA for MHC-II and the transcription
      factor CIITA is inhibited in DCs treated with TLR agonists but maintained in
      cells treated with IFN-I. After stimulation with IFN-I, MHC-II expression is
      increased on the plasma membrane but is also maintained in intracellular vacuolar
      compartments, consistent with sustained Ag processing function. These findings
      suggest that IFN-I drives a distinctive DC maturation program that enhances Ag
      presentation to T cells without a shutdown of Ag processing, allowing continued
      sampling of Ags for presentation.

PMID- 22371392
TI  - Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and
      nonhematopoietic cells during host response to Chikungunya infection.
AB  - The host response to Chikungunya virus is dependent on the direct action of type
      I IFN on infected nonhematopoietic cells. Prior studies have demonstrated that
      multiple host sensors coordinate an antiviral response; however, the tissue
      source(s) and signaling pathways for IFN production remain unknown. In this
      study, we demonstrate that IRF-3 and IRF-7 are functionally redundant, but lack
      of both factors results in lethal infection in adult mice. Reciprocal bone marrow
      chimeras indicated that IRF-3 or IRF-7 expression in either hematopoietic or
      nonhemotopoietic cell compartments was capable of inducing an antiviral response.
      Interestingly, redundancy of IRF-3 and IRF-7 was age dependent, as neonatal
      animals lacking either factor succumbed to infection. We further demonstrate that
      IPS-1 is essential in nonhematopoietic cells and preferentially required during
      early life. These results highlight the interplay between nonimmune and immune
      cells during Chikungunya virus infection and suggest an important role for
      nonhematopoietic cells as a critical source of IFN-alpha/beta.

PMID- 22371393
TI  - The Lbw2 locus promotes autoimmune hemolytic anemia.
AB  - The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically
      imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very
      similar to the corresponding human disease. Previous studies have mapped anti
      erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations,
      including chromosome 4; however, none of these have been analyzed with interval
      congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2
      congenic) mice containing an introgressed fragment of New Zealand White (NZW) on
      chromosome 4 encompassing Lbw2, a locus previously linked to survival,
      glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2
      congenic mice exhibited marked reductions in AEAs and splenomegaly but not in
      anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal
      zone B cells and reduced expansion of peritoneal cells, particularly the B-1a
      cell subset at early ages, but no reduction in B cell response to LPS. Analysis
      of a panel of subinterval congenic mice showed that the full effect of Lbw2 on
      AEA production was dependent on three subloci, with splenomegaly mapping to two
      of the subloci and expansions of peritoneal cell populations, including B-1a
      cells to one. These results directly demonstrated the presence of AEA-specific
      promoting genes on NZB chromosome 4, documented a marked influence of background
      genes on autoimmune phenotypes related to Lbw2, and further refined the locations
      of the underlying genetic variants. Delineation of the Lbw2 genes should yield
      new insights into both the pathogenesis of AIHA and the nature of epistatic
      interactions of lupus-modifying genetic variants.

PMID- 22371394
TI  - CD4(+) type II NKT cells mediate ICOS and programmed death-1-dependent regulation
      of type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell
      mediated destruction of pancreatic beta cells. CD1d-restricted NKT lymphocytes
      have the ability to regulate immunity, including autoimmunity. We previously
      demonstrated that CD1d-restricted type II NKT cells, which carry diverse TCRs,
      prevented T1D in the NOD mouse model for the human disease. In this study, we
      show that CD4(+) 24alphabeta type II NKT cells, but not CD4/CD8 double-negative
      NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells
      in adoptive transfer experiments. CD4(+) 24alphabeta NKT cells exhibited a memory
      phenotype including high ICOS expression, increased cytokine production, and
      limited display of NK cell markers, compared with double-negative 24alphabeta NKT
      cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1
      pathway was shown to abolish the regulation that occurred in the pancreas
      draining lymph nodes. To our knowledge, these results provide for the first time
      cellular and molecular information on how type II CD1d-restricted NKT cells
      regulate T1D.

PMID- 22371395
TI  - Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues,
      lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a
      novel Il-33-LacZ gene trap reporter strain.
AB  - IL-33 (previously known as NF from high endothelial venules) is an IL-1 family
      cytokine that signals through the ST2 receptor and drives cytokine production in
      mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes,
      and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper
      2 cells). Little is known about endogenous IL-33; for instance, the cellular
      sources of IL-33 in mouse tissues have not yet been defined. In this study, we
      generated an Il-33-LacZ gene trap reporter strain (Il-33(Gt/Gt)) and used this
      novel tool to analyze expression of endogenous IL-33 in vivo. We found that the
      Il-33 promoter exhibits constitutive activity in mouse lymphoid organs,
      epithelial barrier tissues, brain, and embryos. Immunostaining with anti-IL-33
      Abs, using Il-33(Gt/Gt) (Il-33-deficient) mice as control, revealed that
      endogenous IL-33 protein is highly expressed in mouse epithelial barrier tissues,
      including stratified squamous epithelia from vagina and skin, as well as cuboidal
      epithelium from lung, stomach, and salivary gland. Constitutive expression of IL
      33 was not detected in blood vessels, revealing the existence of species-specific
      differences between humans and mice. Importantly, IL-33 protein was always
      localized in the nucleus of producing cells with no evidence for cytoplasmic
      localization. Finally, strong expression of the Il-33-LacZ reporter was also
      observed in inflamed tissues, in the liver during LPS-induced endotoxin shock,
      and in the lung alveoli during papain-induced allergic airway inflammation.
      Together, our findings support the possibility that IL-33 may function as a
      nuclear alarmin to alert the innate immune system after injury or infection in
      epithelial barrier tissues.

PMID- 22371396
TI  - SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in
      human asthmatic airway epithelial cells.
AB  - Asthma is a chronic inflammatory disease in which airway epithelial cells are the
      first line of defense against exposure of the airway to infectious agents. Src
      homology protein (SHP)-1, a protein tyrosine phosphatase, is a negative regulator
      of signaling pathways that are critical to the development of asthma and host
      defense. We hypothesize that SHP-1 function is defective in asthma, contributing
      to the increased inflammatory response induced by Mycoplasma pneumoniae, a
      pathogen known to exacerbate asthma. M. pneumoniae significantly activated SHP-1
      in airway epithelial cells collected from nonasthmatic subjects by bronchoscopy
      with airway brushing but not in cells from asthmatic subjects. In asthmatic
      airway epithelial cells, M. pneumoniae induced significant PI3K/Akt
      phosphorylation, NF-kappaB activation, and IL-8 production compared with
      nonasthmatic cells, which were reversed by SHP-1 overexpression. Conversely, SHP
      1 knockdown significantly increased IL-8 production and PI3K/Akt and NF-kappaB
      activation in the setting of M. pneumoniae infection in nonasthmatic cells, but
      it did not exacerbate these three parameters already activated in asthmatic
      cells. Thus, SHP-1 plays a critical role in abrogating M. pneumoniae-induced IL-8
      production in nonasthmatic airway epithelial cells through inhibition of PI3K/Akt
      and NF-kappaB activity, but it is defective in asthma, resulting in an enhanced
      inflammatory response to infection.

PMID- 22371399
TI  - [Maternal obesity and the development of skeletal muscle in offspring--fetal
      origin of metabolic disorders].
AB  - Suboptimal fetal environments due to inadequate maternal nutrition, obesity,
      inflammation or gestational diabetes expose the fetus to humoral cues that alter
      metabolism and growth parameters leading to metabolic disturbances later in life.
      The fetal stage is crucial for the development of skeletal muscle, a tissue
      playing an important role in metabolism. Maternal obesity induces inflammation in
      the fetus causing modifications in the development of fetal skeletal muscle.
      Changes in the normal course of myogenesis may arise through several mechanisms:
      changes in WNT/beta-catenin signaling pathway, decreased AMPK activity evoked by
      TNF-alpha, increased activity of NF-kappaB in response to inflammation, which
      leads to a decrease in myogenic factor MyoD, and increased expression of TGF
      beta1. Modification in fetal development associated with maternal obesity is
      attributed to epigenetic changes. Polyunsaturated fatty acids supplied in the
      diet did affect the development of insulin-sensitive tissues during both the
      fetal and postnatal period. The specific phenotype of skeletal muscle fibers may
      play a role in the development of obesity, i.e. fiber phenotype I (slow,
      oxidative) may protect against obesity and insulin resistance. Exploring the
      mechanisms of direct impact of maternal obesity on the development of tissues in
      the offspring may help to reduce the occurrence of metabolic diseases in later
      life.

PMID- 22371398
TI  - Murine membranous nephropathy: immunization with alpha3(IV) collagen fragment
      induces subepithelial immune complexes and FcgammaR-independent nephrotic
      syndrome.
AB  - Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults
      and a significant cause of end-stage renal disease, yet current therapies are
      nonspecific, toxic, and often ineffective. The development of novel targeted
      therapies requires a detailed understanding of the pathogenic mechanisms, but
      progress is hampered by the lack of a robust mouse model of disease. We report
      that DBA/1 mice as well as congenic FcgammaRIII(-/-) and FcRgamma(-/-) mice
      immunized with a fragment of alpha3(IV) collagen developed massive albuminuria
      and nephrotic syndrome, because of subepithelial deposits of mouse IgG and C3
      with corresponding basement membrane reaction and podocyte foot process
      effacement. The clinical presentation and histopathologic findings were
      characteristic of MN. Although immunized mice produced genuine anti-alpha3NC1
      autoantibodies that bound to kidney and lung basement membranes, neither
      crescentic glomerulonephritis nor alveolitis ensued, likely because of the
      predominance of mouse IgG1 over IgG2a and IgG2b autoantibodies. The ablation of
      activating IgG Fc receptors did not ameliorate injury, implicating subepithelial
      deposition of immune complexes and consequent complement activation as a major
      effector pathway. We have thus established an active model of murine MN. This
      model, leveraged by the availability of genetically engineered mice and mouse
      specific reagents, will be instrumental in studying the pathogenesis of MN and
      evaluating the efficacy of novel experimental therapies.

PMID- 22371397
TI  - CARMA1 controls Th2 cell-specific cytokine expression through regulating JunB and
      GATA3 transcription factors.
AB  - The scaffold protein CARMA1 is required for the TCR-induced lymphocyte
      activation. In this study, we show that CARMA1 also plays an essential role in T
      cell differentiation. We have found that the adoptive transfer of bone marrow
      cells expressing constitutively active CARMA1 results in lung inflammation,
      eosinophilia, and elevated levels of IL-4, IL-5, and IL-10 in recipient mice. In
      contrast, CARMA1-deficient T cells are defective in TCR-induced expression of Th2
      cytokines, suggesting that CARMA1 preferentially directs Th2 differentiation. The
      impaired cytokine production is due to reduced expression of JunB and GATA3
      transcription factors. CARMA1 deficiency affects JunB stability resulting in its
      enhanced ubiquitination and degradation. In contrast, TCR-dependent induction of
      GATA3 is suppressed at the transcriptional level. We also found that
      supplementation with IL-4 partially restored GATA3 expression in CARMA1-deficient
      CD4(+) splenocytes and subsequently production of GATA3-dependent cytokines IL-5
      and IL-13. Therefore, our work provides the mechanism by which CARMA1 regulates
      Th2 cell differentiation.

PMID- 22371400
TI  - Dietary patterns as risk factors of differentiated thyroid carcinoma.
AB  - Nutritional factors are known to be important in the development of different
      metabolic diseases. The history of nodular or diffuse goiter is closely related
      to risk of thyroid carcinoma. On account of the function of the thyroid gland,
      many studies focus on iodine intake.    The aim of the study was to assess
      whether dietary patterns could be risk factors of differentiated thyroid
      carcinoma. MATERIAL/METHODS: The case-control study was based on a questionnaire,
      which included information about dietary patterns and was carried out on 284
      patients comprising 30 males (mean age 58.4+/-13.7 years), and 254 females (mean
      age 52.1+/-13.8 years), as well as 345 randomly selected controls: 58 males (mean
      age 60.2+/-12 years) and 287 females (mean age 53.4+/-14.3 years) randomly
      selected from the Population Register and adjusted by age and gender to the group
      of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy
      products, vegetables, fruits, and beverages, were analyzed. RESULTS: Consumption
      of vegetables, fruits, saltwater fish and cottage cheese was significantly lower
      in patients with differentiated thyroid carcinoma than in controls, quite the
      contrary to starchy foods, especially white bread. CONCLUSIONS: Dietary patterns
      appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and
      fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be
      an important protective factor.

PMID- 22371401
TI  - Effects of lactoferrin on elicitation of the antigen-specific cellular and
      humoral cutaneous response in mice.
AB  - Immune contact dermatitis is an inflammation of the skin resulting from exposure
      to allergens in the environment. The aim of this study was to compare the actions
      of lactoferrin (LF), a natural immunomodulator, on the elicitation phases of the
      cellular and humoral, cutaneous immune responses to oxazolone and toluene
      diisocyanate (TDI), respectively. LF was given i.v. in a 10 mg/mouse dose,
      together with the eliciting doses of the antigens. The ear edema and the number
      of lymphocytes in the draining lymph nodes were measured. In addition, the
      production of IL-2 in the cultures of lymph node cells and the content of IL-4 in
      lymph node cells were determined. LF had a profound inhibitory effect on the
      eliciting phase of the immune response to oxazolone as measured by the ear edema
      and lymph node cell number. The suppressive effect of LF on the effector phase of
      the immune response to TDI was moderate. LF had some stimulatory effect on the ex
      vivo content of IL-4 in lymphocytes in the immune response to TDI. On the other
      hand, it significantly inhibited IL-2 in vitro production in the immune response
      to oxazolone. The data strongly suggest that LF exerted differential actions on
      the activities of antigen-specific Th1 and Th2 cells involved in respective types
      of the cutaneous immune responses.

PMID- 22371402
TI  - [Molecular and cytogenetic evidence for the development of fibroids].
AB  - Uterine fibroids are the most common benign tumor of the female genital tract.
      Their epidemiology is probably highly underestimated because a high percentage of
      them are in the asymptomatic stage. The etiology of fibroids and their biology
      are still poorly understood, although steroid ovarian hormones, both estrogen and
      progestins, have played an important role in etiopathogenesis of this disease.
      Also no single candidate gene has been detected for commonly occurring uterine
      fibroids. Cytogenetic abnormalities, particularly translocation, duplication and
      deletions of chromosome 7, which are found in up to 50% of fibroid specimens,
      seem to play an important role during abnormal transformation of uterus smooth
      muscle. The key regulators that transform normal uterine tissue to fibroids are
      growth factors (VEGF, TGF, PDGF, etc.), angiogenesis and the process of
      apoptosis.    In this review, current knowledge about molecular and cytogenetic
      evidence on fibroid development is presented.

PMID- 22371403
TI  - [Regulation of melanogenesis: the role of cAMP and MITF].
AB  - The article presents the melanogenesis pathway and the role of cyclic adenosine
      monophosphate (cAMP) and microphthalmia transcription factor (MITF) in regulation
      of this process. Products of melanogenesis are eu- and/or pheomelanins
      synthesized in a multistage process of tyrosine oxidation and polymerization. The
      conversions require the presence of tyrosinase (TYR, key enzyme), tyrosine
      hydroxylase isoform I (THI) and tyrosinase related proteins (TRP1 and TRP2). Many
      types of signal molecules and transcription factors participate in regulation of
      melanin synthesis, but the most important are cAMP and MITF. cAMP is the second
      messenger in the intracellular signal cascade, which is synthesized from
      adenosine triphosphate (ATP) by adenylyl cyclase, activated among others by the
      melanocortin receptor and the alphaS subunit of G protein. The signal molecule
      cAMP regulates MITF, TYR, THI, GTP-cyclohydroxylase I (GTP-CHI) transcription and
      phenylalanine hydroxylase (PAH) phosphorylation at Ser16 by protein kinase A
      (PKA). Mutations of genes encoding proteins belonging to the cAMP signal cascade
      may lead to McCune-Albright and Carney syndromes. MITF is one of the most
      important nuclear transcription factors regulating melanogenesis. Currently 10
      isoforms of human MITF are known, but in melanocytes only MITF-M, MITF-Mdel, MITF
      A and MITF-H occur. MITF transcription factor regulates melanogenesis by
      activation of tyrosinase, TRP1 and TRP2 transcription. It also affects expression
      of other factors regulating melanosome maturation, biogenesis and transport.
      Moreover, it regulates melanocyte proliferation and protection against apoptosis.
      Mutations of the MITF gene may lead to hereditary diseases: Waardenburg type II
      and Tietz syndromes.

PMID- 22371404
TI  - Etiology of thrombosed external hemorrhoids.
AB  - INTRODUCTION: External hemorrhoids are located outside of the dentate line and
      covered by anoderm. Thrombosed external hemorrhoids are one of the frequent acute
      anorectal diseases which are treated successfully in the proctology outpatient
      room. The etiology of this disease is still unknown. Knowledge of the etiology of
      thrombosed external hemorrhoids could prevent recurrence of this disease and help
      prepare good prophylaxis. MATERIAL/METHODS: A group of 50 patients with a
      diagnosis of thrombosed external hemorrhoids and treated in the Mikolaj Pirogow
      Regional Specialist Hospital in Lodz was interviewed by means of the author's own
      questionnaire concerning demography and published hypothesis. The necessary
      statistics were conducted by means of STATISTICA 7.1 and EXCEL 2008 programs.
      RESULTS: The analysis of the survey results shows a significant relationship of
      thrombosed external hemorrhoids and presence of internal hemorrhoids, practice of
      anoreceptive sex and consumption of more alcohol products than usual. There was
      no statistical relationship between lifting heavy objects, eating spicy food,
      having hard stools or straining at toilet during motions and thrombosed external
      hemorrhoids. CONCLUSIONS: This study confirmed three hypotheses on the causes of
      thrombosed external hemorrhoids which were presented in medical journals
      available in the MEDLINE database. The author of this article believes that it is
      necessary to conduct a multi-center study, which would explain the exact etiology
      of this disease. Knowledge about the etiology of thrombosed external disease
      would help develop effective prevention and treatment.

PMID- 22371405
TI  - Effect of preservation solutions UW and EC on the expression of matrix
      metalloproteinase II and tissue inhibitor of metalloproteinase II genes in rat
      kidney.
AB  - Matrix metalloproteinases and tissue inhibitor of metalloproteinases play an
      important role in the regulation of mesangial cell proliferation and may be
      involved in ischemia-reperfusion injuries. Preservation solutions are thought to
      diminish the ischemic injury and appropriate choice of the solution should
      guarantee a better graft function and good prognosis for graft survival. The aim
      of the study was to examine the effect of preservation solutions UW and EC on the
      expression of matrix metalloproteinase II and tissue inhibitor of
      metalloproteinase II genes in rat kidney.    The study was carried out on Wistar
      rat kidneys divided into 3 groups: kidneys perfused with 0.9% NaCl (control
      group), with UW, and with EC preservation solution.    The results show an
      enhancement of MMP-2 and TIMP-2 gene expression after 12 min of cold ischemia.
      This increase was more expressed in kidneys preserved with UW solution in
      comparison with kidneys perfused with EC solution and 0.9% NaCl. After 24 h of
      cold ischemia the expression of MMP-2 and TIMP-2 genes in kidney perfused with UW
      solution decreased, while in kidneys perfused with EC it was increased. After
      warm ischemia the MMP-2 and TIMP-2 gene expression increased, whereas it was
      significantly lower in kidneys perfused with EC solution.

PMID- 22371406
TI  - Diabetic microangiopathy in capillaroscopic examination of juveniles with
      diabetes type 1.
AB  - INTRODUCTION: The aim of this work was a quantitative and qualitative assessment
      of a selected part of the microcirculation in children with diabetes type 1 using
      videocapillaroscopy technique. MATERIAL/METHODS: The authors tested a group
      consisting of 145 children (70 boys, 75 girls) diagnosed and treated for diabetes
      type 1 in the Diabetic Clinic of GCZD in Katowice for at least one year. The
      study included history, clinical examination (including dermatological
      examination) and videocapillaroscopy. Capillaroscopy, a non-invasive, painless
      and easily repeatable test, was performed using videocapillaroscopy with digital
      storage of the obtained images. All nailfolds were examined in all children using
      videocapillaroscopy, and the obtained images were assessed quantitatively and
      qualitatively for changes in capillary loops in the tested children according to
      the defined diagnostic procedure. RESULTS: The analysis of capillaroscopic images
      described selected quantitative and qualitative characteristics. The conducted
      analysis showed an increase in the number of capillaries and their elongation,
      the presence of megacapillaries and Raynaud loops, which were accompanied by an
      intensive red background, indicating possible neoangiogenesis. The increase in
      the number of capillaries, disturbances in distribution of capillaries and the
      presence of abnormal capillaries were correlated with the longer duration of
      diabetes. Raynaud loops were more frequently found in the cases of increased mean
      values of HbA1c. Higher values of HbA1c influenced the capillaroscopic images,
      mainly the number of vessels, including Raynaud loops. CONCLUSIONS:
      Videocapillaroscopy technique could be a useful tool to detect the early changes
      of microangiopathy in children with diabetes type 1.

PMID- 22371407
TI  - [The role of gastric mucins in interactions with Helicobacter pylori].
AB  - Helicobacter pylori is a Gram-negative bacterium which colonizes the stomach of
      over 50% of the world's population. The pathogen is responsible for many diseases
      including gastritis, ulcers and also gastric cancers. It is said that adherence
      of bacteria to epithelial cells plays a key role in infection development. Two
      gastric mucins, components of mucus, are assumed to have an important role in
      protection against adhesion and in this way in progression of infection. These
      are a secretory MUC5AC mucin, produced by mucous epithelial cells, and a membrane
      bound MUC1 mucin, expressed by epical surfaces of epithelial cells. Interactions
      with bacteria occur between carbohydrate antigens of mucins and specific adhesins
      of the Helicobacter pylori surface. In this paper we present the latest knowledge
      about these intriguing interactions of both mucins and their interplay with the
      pathogen providing protection against infection.

PMID- 22371408
TI  - [BH3 mimetics as a strategy to complement anticancer therapies].
AB  - The basis for targeting specific components of the apoptotic machinery for
      anticancer therapy is the detailed knowledge on molecular mechanisms that
      regulate this complex cell death pathway. As the mitochondrial pathway of
      apoptosis is the major route to respond to stress stimuli including anticancer
      drugs, and that pathway is largely impaired in cancer cells, leading to tumor
      formation and treatment resistance, a variety of approaches have been developed
      to restore the function of the mitochondrial pathway in cancer cells. BH3-only
      proteins, being important inducers of the mitochondrial pathway, either directly
      stimulate proapoptotic Bax-like proteins or interfere with antiapoptotic Bcl-2
      proteins. Therefore, the development of molecules able to mimic the function of
      BH3-only proteins is considered a promising strategy to improve cancer cell
      response to treatment. Several BH3 mimetics have been designed and studied in
      various tumors, in both in vitro and in vivo settings. Some of them are currently
      being evaluated in clinical trials either alone or in combination with
      conventional anticancer drugs. BH3 profiling of cancer cells was introduced to
      better predict the responsiveness of tumor cells to BH3 mimetics combined with
      conventional therapies. In this review, we summarize the current knowledge on BH3
      only proteins and describe the spectrum of strategies employing BH3 mimetics in
      preclinical and clinical studies that aim at tumor targeting.

PMID- 22371409
TI  - Short-term antihypertensive therapy lowers the C-reactive protein level.
AB  - INTRODUCTION: There is a growing body of data concerning significant interactions
      between markers of inflammation and cardiovascular diseases such as hypertension
      accompanied by elevated levels of plasma C-reactive protein (CRP). Therefore CRP
      is thought to be an independent risk factor of cardiovascular diseases.
      MATERIAL/METHODS: The aim of this study was to evaluate the effects of
      antihypertensive therapy (perindopril, bisoprolol and combined therapy) on plasma
      CRP concentration in 67 subjects with mild or moderate hypertension who have been
      treatment-naive and otherwise healthy. RESULTS: The results show a correlation
      between CRP level and blood pressure values. BP reduction was associated with a
      decrease in CRP concentration. The CRP-lowering effect of perindopril and
      bisoprolol was comparable and the degree of reduction might reflect their similar
      influence on blood pressure. Combined treatment influenced the CRP level to a
      greater extent than both monotherapies. CONCLUSIONS: Plasma CRP level was lowered
      by antihypertensive therapy independently of the drug applied. The CRP level did
      not normalize completely in moderate hypertensive patients.

PMID- 22371410
TI  - [Searching for Tourette's syndrome gene. Part 1. Heterogeneity of clinical
      phenotypes].
AB  - The French neuropsychiatrist Georges Gilles de la Tourette described in 1885 the
      "Maladie des Tics" which later was named after him, as Gilles de la Tourette
      syndrome (GTS). Gilles de la Tourette syndrome is a neurodevelopmental disorder
      characterized by simple and complex motor and vocal tics with multiple
      neuropsychiatric comorbidities. GTS is often concurrent with obsessive-compulsive
      disorder (OCD) and attention deficit hyperactivity disorder (ADHD). There are
      several clinical GTS subtypes: GTS only, GTS+OCD, and GTS+OCD+ADHD. Additional
      clinical aspects of the disorder include occurrence of anger episodes, anxiety
      and mood disorders, and learning and sleeping disturbances. The genetics of GTS
      is complex and remains unclear. So far, no causative candidate genes have been
      identified. However, segregation studies in families and twins with GTS provide
      strong evidence for the existence of a genetic background associated with a
      multifactorial mode of inheritance. Progress in studies on genome variability
      among patients with GTS is necessary to improve pharmacotherapeutic strategies of
      the disorder.

PMID- 22371411
TI  - [Searching for Tourette's syndrome gene. Part 2. Patient's genome variability].
AB  - Gilles de la Tourette syndrome (GTS) is a complex, heterozygous genetic disorder.
      Twenty chromosomal rearrangements (7q22-q31, 8q13-q22, and 18q22) indicating
      genomic regions which may be involved in the etiology of the disorder have been
      reported in families with GTS. Moreover, pathogenic mutations responsible for GTS
      were found in the SLITRK1 and the L-histidine decarboxylase (HDC) genes. The
      W317X mutation in the HDC gene points to a possible role for histaminergic
      neurotransmission in the mechanism and modulation of tic disorder. The
      distribution of single nucleotide polymorphisms (SNPs) was examined in at least
      14 candidate genes (DRD1, DRD2, DRD3, DRD4, DAT1, MAOA, 5HTR2A, 5HTR3A, TDO2,
      CNR1, HLA-DRB, IL1RA, MOG, and SGCE) using a case-control genetic association
      analysis. Still, a lack of replicated and consistent results was observed.
      Recently, rare structural variants of different genes involved in
      neurodevelopment determined by recurrent exonic copy number variations (CNVs)
      have been found in a subset of patients suffering from GTS.

PMID- 22371412
TI  - Infection cases in infants and small children with atopic dermatitis--own
      observations.
AB  - INTRODUCTION: The purpose of the work is to estimate the frequency of occurrence
      of various infections in infants and small children, aged between 0 and 36 months
      with atopic dermatitis in the practice of a family doctor. MATERIAL/METHODS: The
      study has been conducted on the basis of the retrospective analysis of medical
      documentation of disease among children born in 2005-2008 treated in Outpatient
      Clinic of the Polish Mother's Memorial Hospital in Lodz. RESULTS: Children
      suffering from atopic dermatitis are more prone to develop infectious diseases.
      CONCLUSIONS: Infectious diseases in children with atopic dermatitis are of more
      chronic nature and more often require antibiotic therapy. Such children often
      manifest chronic diarrhea and their stool contains Staphylococcus aureus. They
      are more often hospitalized because of difficulty in setting a diagnosis and
      applying treatment in outpatient clinics.

PMID- 22371413
TI  - Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging.
AB  - OBJECTIVE: Higher dietary intake and circulating levels of docosahexaenoic acid
      (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for
      dementia, but the pathways underlying this association remain unclear. We
      examined the cross-sectional relation of red blood cell (RBC) fatty acid levels
      to subclinical imaging and cognitive markers of dementia risk in a middle-aged to
      elderly community-based cohort. METHODS: We related RBC DHA and EPA levels in
      dementia-free Framingham Study participants (n = 1575; 854 women, age 67 +/- 9
      years) to performance on cognitive tests and to volumetric brain MRI, with serial
      adjustments for age, sex, and education (model A, primary model), additionally
      for APOE epsilon4 and plasma homocysteine (model B), and also for physical
      activity and body mass index (model C), or for traditional vascular risk factors
      (model D). RESULTS: Participants with RBC DHA levels in the lowest quartile (Q1)
      when compared to others (Q2-4) had lower total brain and greater white matter
      hyperintensity volumes (for model A: beta +/- SE = -0.49 +/- 0.19; p = 0.009, and
      0.12 +/- 0.06; p = 0.049, respectively) with persistence of the association with
      total brain volume in multivariable analyses. Participants with lower DHA and
      omega-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests
      of visual memory (beta +/- SE = -0.47 +/- 0.18; p = 0.008), executive function
      (beta +/- SE = -0.07 +/- 0.03; p = 0.004), and abstract thinking (beta +/- SE = 
      0.52 +/- 0.18; p = 0.004) in model A, the results remaining significant in all
      models. CONCLUSION: Lower RBC DHA levels are associated with smaller brain
      volumes and a "vascular" pattern of cognitive impairment even in persons free of
      clinical dementia.

PMID- 22371414
TI  - Fingolimod-associated macular edema: incidence, detection, and management.
AB  - Fingolimod (FTY-720), a sphingosine-1-phosphate receptor modulator, is the first
      US Food and Drug Administration (FDA)-approved oral agent for the treatment of
      relapsing forms of multiple sclerosis (MS). Two recent phase III clinical studies
      (TRANSFORMS [Trial Assessing Injectable Interferon vs FTY720 Oral in RRMS] and
      FREEDOMS [FTY720 Research Evaluating Effects of Daily Oral Therapy in MS])
      demonstrated a significant reduction in the annualized relapse rate in patients
      with relapsing-remitting MS, compared to once weekly interferon beta-1a and
      placebo. Macular edema was a prominent adverse event reported in these and prior
      studies of fingolimod. Thirteen of 2,564 (0.5%) patients treated with fingolimod
      in FREEDOMS and TRANSFORMS developed macular edema. Fingolimod-associated macular
      edema (FAME) appears to be dose-dependent (observed in only 2 patients taking the
      FDA-approved 0.5 mg dose) and typically resolves upon cessation of therapy.
      Although a relatively common condition in ophthalmology, most neurologists have
      not encountered macular edema in clinical practice. The purpose of this review is
      to educate the neurologist on the etiology, clinical manifestations, diagnostic
      modalities, and treatment approaches in patients with FAME. We also discuss the
      use of fingolimod in patients with uveitis and diabetes mellitus, highlight the
      guidelines for surveillance ophthalmic examination, and outline the key
      distinguishing features between FAME and optic neuritis.

PMID- 22371415
TI  - Parkinson disease: the enteric nervous system spills its guts.

PMID- 22371416
TI  - Neurology and neurologic practice in China.

PMID- 22371417
TI  - Pearls & oy-sters: Acute spinal cord infarction following endoscopic ultrasound
      guided celiac plexus neurolysis.

PMID- 22371418
TI  - International Issues: Neurology mission in the Ecuadorian Amazon rainforest.

PMID- 22371419
TI  - Teaching neuroimages: MRI "target sign" and neurofibromatosis type 1.

PMID- 22371420
TI  - Patient page. Cavernous hemangiomas.

PMID- 22371421
TI  - Integration of vole management in boreal silvicultural practices.
AB  - Voles of the genera Microtus and Myodes are widespread and among the most
      abundant of small mammal species in the boreal zone of the Northern Hemisphere.
      They are keystone herbivore species in northern ecosystems, and they have
      profound impacts on both higher and lower trophic levels. Voles are also major
      silvicultural pests, damaging millions of tree seedlings in years of peak
      abundance. Prevention of vole damage to silviculture has proven to be very
      difficult owing to the ubiquity of both suitable vole habitat and potential
      damage sites across landscapes. The degree of damage inflicted by voles on
      seedling stands is largely, but not solely, determined by prevailing vole
      densities, which often fluctuate in 3-4 year population cycles. Silvicultural
      practices related to site habitat manipulation and/or choice and rearing of
      seedling material may also greatly influence the severity of vole damage to
      seedlings. The manipulation of these practices is currently at the forefront of
      methods potentially applicable to control vole damage in boreal forests. This
      paper reviews current evidence for the efficacy and present recommendations for
      further development and application of these methods to mitigate vole damage to
      seedling stands in boreal silviculture.

PMID- 22371422
TI  - Monitoring of aglycons of yew glycosides (3,5-dimethoxyphenol, myrtenol and 1
      octen-3-ol) as first indicator of yew presence.
AB  - The toxicity of yew (Taxus spp) is well known from ancient times and is mainly
      due to taxins acting as inhibitors of calcium and sodium transport across the
      cell membrane of cardiac myocytes. The confirmation of yew taxins in body fluids
      can be carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      However, before selecting this precise but expensive technique, an orientation
      test should be done to ascertain yew presence as toxic agent in the organism. As
      the 3,5-dimethoxyphenol (3,5-DMP), myrtenol and 1-octen-3-ol appear as
      glycosidically bound volatile compounds and are very yew specific, the detection
      of 3,5-DMP and the measurement of 1-octen-3-ol / myrtenol concentration ratio
      constitute reliable indicators of yew presence in forensic cases. The detection
      of these compounds is easily performed by gas chromatography-mass spectrometry
      (GC-MS) (SIM) after an enzymatic hydrolysis (beta-glucosidase) allowing the
      release of volatile compounds from yew glycosides.

PMID- 22371423
TI  - Modeling the role of IL2 in the interplay between CD4+ helper and regulatory T
      cells: studying the impact of IL2 modulation therapies.
AB  - Several reports in the literature have drawn a complex picture of the effect of
      treatments aiming to modulate IL2 activity in vivo. They seem to promote
      indistinctly immunity or tolerance, probably depending on the specific context,
      dose and timing of their application. Such complexity might derives from the dual
      role of IL2 on T-cell dynamics. To theoretically address the latter possibility,
      we develop a mathematical model for helper, regulatory and memory T-cells
      dynamics, which account for most well-known facts relative to their relationship
      with IL2. We simulate the effect of three types of therapies: IL2 injections, IL2
      depletion using anti-IL2 antibodies and IL2/anti-IL2 immune complexes injection.
      We focus in the qualitative and quantitative conditions of dose and timing for
      these treatments which allow them to potentate either immunity or tolerance. Our
      results provide reasonable explanations for the existent pre-clinical and
      clinical data and further provide interesting practical guidelines to optimize
      the future application of these types of treatments. Particularly, our results
      predict that: (i) Immune complexes IL2/anti-IL2 mAbs, using mAbs which block the
      interaction of IL2 and CD25 (the alpha chain of IL2 receptor), is the best option
      to potentate immunity alone or in combination with vaccines. These complexes are
      optimal when a 1:2 molar ratio of mAb:IL2 is used and the mAbs have the largest
      possible affinity; (ii) Immune complexes IL2/anti-IL2 mAbs, using mAbs which
      block the interaction of IL2 and CD122 (the beta chain of IL2 receptor), are the
      best option to reinforce preexistent natural tolerance, for instance to prevent
      allograft rejection. These complexes are optimal when a 1:2 molar ratio of
      mAb:IL2 is used and the mAbs have intermediate affinities; (iii) mAbs anti-IL2
      can be successfully used alone to treat an ongoing autoimmune disorder, promoting
      the re-induction of tolerance. The best strategy in this therapy is to start
      treatment with an initially high dose of the mAbs (one capable to induce some
      immune suppression) and then scales down slowly the dose of mAb in subsequent
      applications.

PMID- 22371424
TI  - Designing the ideal habitat for entomopathogen use in nursery production.
AB  - BACKGROUND: Greenhouse and nursery producers use entomopathogens (nematodes and
      fungi) to control soil pests. Although it is known that the physical and chemical
      properties of mineral soil significantly impact upon soil pathogens, the
      influence of soilless media used for plant production on entomopathogen
      performance is poorly understood. RESULTS: Survival and foraging distance were
      differently affected by sand:peat, bark and sawdust media for entomopathogenic
      nematodes, but not for the immobile fungus Metarhizium anisopliae. Redwood
      sawdust medium consistently had a negative impact upon entomopathogenic
      nematodes. Dividing media into individual components supported the hypothesis
      that redwood sawdust reduced foraging and infection abilities of S. riobrave and
      H. bacteriophora. Physically altering the components by adding sand significantly
      improved foraging and infection success for S. riobrave in media not optimum for
      foraging. CONCLUSION: This study is the first to highlight the importance of
      selecting the appropriate soilless media and pathogen species combinations to
      increase efficacy of biological control. H. bacteriophora was able to find hosts
      in a wider diversity of medium components than S. riobrave, although both
      nematode species performed well in peat moss and recycled plant material. These
      results suggest that peat moss, recycled plant material and hardwood bark are
      components amenable to EPN biological control programs.

PMID- 22371425
TI  - A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines
      in humans: 1955-2010.
AB  - Three indole alkaloids that possess differing degrees of psychotropic/psychedelic
      activity have been reported as endogenous substances in humans; N,N
      dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT
      (MDMT). We have undertaken a critical review of 69 published studies reporting
      the detection or detection and quantitation of these compounds in human body
      fluids. In reviewing this literature, we address the methods applied and the
      criteria used in the determination of the presence of DMT, MDMT, and HDMT. The
      review provides a historical perspective of the research conducted from 1955 to
      2010, summarizing the findings for the individual compounds in blood, urine,
      and/or cerebrospinal fluid. A critique of the data is offered that addresses the
      strengths and weaknesses of the methods and approaches to date. The review also
      discusses the shortcomings of the existing data in light of more recent findings
      and how these may be overcome. Suggestions for the future directions of
      endogenous psychedelics research are offered.

PMID- 22371426
TI  - Green tea consumption and gastric cancer risk: an evaluation based on a
      systematic review of epidemiologic evidence among the Japanese population.
AB  - OBJECTIVE: Numerous in vitro and animal studies have shown that green tea has a
      protective effect against cancer. However, results from epidemiologic studies are
      conflicting. We evaluated the association between green tea consumption and risk
      for gastric cancer risk among the Japanese population based on a systematic
      review of epidemiologic evidence. METHODS: Original data were obtained from
      MEDLINE searches using PubMed or from searches of the Ichushi database,
      complemented with manual searches. Evaluation of associations was based on the
      strength of evidence and the magnitude of association, together with biologic
      plausibility. RESULTS: Eight cohort studies and three case-control studies were
      identified. Overall, we found no preventive effect on gastric cancer for green
      tea intake in cohort studies. However, a small, consistent risk reduction limited
      to women was observed, which was confirmed by pooling data of six cohort studies
      (hazard ratio = 0.79, 95% confidence interval 0.65-0.96 with >=5 cups/day of
      green tea intake). Case-control studies consistently showed a weak inverse
      association between green tea intake and gastric cancer risk. CONCLUSIONS: We
      conclude that green tea possibly decreases the risk of gastric cancer in women.
      However, epidemiologic evidence is still insufficient to demonstrate any
      association in men.

PMID- 22371427
TI  - Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients
      with advanced solid tumors: a Phase 1 dose-escalation study.
AB  - OBJECTIVE: Neratinib (HKI-272), a potent, irreversible, small-molecule, orally
      administered, pan-ErbB inhibitor that blocks signal transduction via inhibition
      of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is
      being developed for the treatment of solid tumors, including breast cancer. This
      Phase 1 dose-escalation study assessed the safety, tolerability, maximum
      tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese
      patients with advanced solid tumors. METHODS: Patients received neratinib 80,
      160, 240 or 320 mg orally; each patient enrolled in only one dose cohort.
      Patients received a single dose in week 1, followed by daily continuous doses.
      Blood samples collected were on days 1 and 21 for pharmacokinetic analyses.
      RESULTS: Twenty-one patients were enrolled (3 breast cancer; 17 colorectal
      cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included
      diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9
      patients each) and anorexia (8 patients). Grade >=3 neratinib-related adverse
      events in two or more patients were diarrhea and anorexia (two patients each).
      Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose).
      The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily.
      Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable
      disease >=24 weeks, 7 had stable disease >=16 weeks and 9 had progressive
      disease. Pharmacokinetic analyses indicated that neratinib exposures increased
      with dose. CONCLUSIONS: The safety, efficacy and pharmacokinetic profiles of
      neratinib are consistent with those reported for non-Japanese patients and
      warrant further investigation of neratinib in Japanese patients with solid
      tumors.

PMID- 22371428
TI  - A new in-camera imaging model for color computer vision and its application.
AB  - We present a study of in-camera image processing through an extensive analysis of
      more than 10,000 images from over 30 cameras. The goal of this work is to
      investigate if image values can be transformed to physically meaningful values,
      and if so, when and how this can be done. From our analysis, we found a major
      limitation of the imaging model employed in conventional radiometric calibration
      methods and propose a new in-camera imaging model that fits well with today's
      cameras. With the new model, we present associated calibration procedures that
      allow us to convert sRGB images back to their original CCD RAW responses in a
      manner that is significantly more accurate than any existing methods.
      Additionally, we show how this new imaging model can be used to build an image
      correction application that converts an sRGB input image captured with the wrong
      camera settings to an sRGB output image that would have been recorded under the
      correct settings of a specific camera.

PMID- 22371429
TI  - Ensemble manifold regularization.
AB  - We propose an automatic approximation of the intrinsic manifold for general semi
      supervised learning (SSL) problems. Unfortunately, it is not trivial to define an
      optimization function to obtain optimal hyperparameters. Usually, cross
      validation is applied, but it does not necessarily scale up. Other problems
      derive from the suboptimality incurred by discrete grid search and the
      overfitting. Therefore, we develop an ensemble manifold regularization (EMR)
      framework to approximate the intrinsic manifold by combining several initial
      guesses. Algorithmically, we designed EMR carefully so it 1) learns both the
      composite manifold and the semi-supervised learner jointly, 2) is fully automatic
      for learning the intrinsic manifold hyperparameters implicitly, 3) is
      conditionally optimal for intrinsic manifold approximation under a mild and
      reasonable assumption, and 4) is scalable for a large number of candidate
      manifold hyperparameters, from both time and space perspectives. Furthermore, we
      prove the convergence property of EMR to the deterministic matrix at rate root-n.
      Extensive experiments over both synthetic and real data sets demonstrate the
      effectiveness of the proposed framework.

PMID- 22371430
TI  - A new unsupervised feature ranking method for gene expression data based on
      consensus affinity.
AB  - Feature selection is widely established as one of the fundamental computational
      techniques in mining microarray data. Due to the lack of categorized information
      in practice, unsupervised feature selection is more practically important but
      correspondingly more difficult. Motivated by the cluster ensemble techniques,
      which combine multiple clustering solutions into a consensus solution of higher
      accuracy and stability, recent efforts in unsupervised feature selection proposed
      to use these consensus solutions as oracles. However,these methods are dependent
      on both the particular cluster ensemble algorithm used and the knowledge of the
      true cluster number. These methods will be unsuitable when the true cluster
      number is not available, which is common in practice. In view of the above
      problems, a new unsupervised feature ranking method is proposed to evaluate the
      importance of the features based on consensus affinity. Different from previous
      works, our method compares the corresponding affinity of each feature between a
      pair of instances based on the consensus matrix of clustering solutions. As a
      result, our method alleviates the need to know the true number of clusters and
      the dependence on particular cluster ensemble approaches as in previous works.
      Experiments on real gene expression data sets demonstrate significant improvement
      of the feature ranking results when compared to several state-of-the-art
      techniques.

PMID- 22371431
TI  - A gene expression profile test for the differential diagnosis of ovarian versus
      endometrial cancers.
AB  - We have developed a gene expression profile test (Pathwork Tissue of Origin
      Endometrial Test) that distinguishes primary epithelial ovarian and endometrial
      cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 316-gene
      classification model. The test was validated in a blinded study using a pre
      specified algorithm and microarray files for 75 metastatic, poorly differentiated
      or undifferentiated specimens with a known ovarian or endometrial cancer
      diagnosis. Measures of test performance include a 94.7% overall agreement with
      the known diagnosis, an area under the ROC curve (AUC) of 0.997 and a diagnostic
      odds ratio (DOR) of 406. Ovarian cancers (n=30) gave an agreement of 96.7% with
      the known diagnosis while endometrial cancers (n=45) gave an agreement of 93.3%.
      In a precision study, concordance in test results was 100%. Reproducibility in
      test results between three laboratories was 94.3%. The Tissue of Origin
      Endometrial Test can aid in resolving important differential diagnostic questions
      in gynecologic oncology.

PMID- 22371432
TI  - Structural investigations on an amorphous Se90Te10 alloy produced by mechanical
      alloying using EXAFS, cumulant expansion and RMC simulations.
AB  - We investigated an amorphous Se(90)Te(10) alloy produced by mechanical alloying
      using two different approaches. First, we used extended x-ray absorption fine
      structure (EXAFS) spectroscopy and the cumulant expansion method using the
      Einstein model for the temperature dependence of the cumulants to obtain the
      cumulants C(*)(1), C(*)(2), and C(*)(3). From these, we found information about
      the structure of the alloy as well as the thermal and structural disorder,
      anharmonicity of the effective interatomic pair potentials, thermal expansion of
      the Se-Se and Se-Te bonds and asymmetry of the partial distribution functions
      g(Se-Se)(r) and g(Se-Te)(r). The cumulants C(*)(1), C(*)(2), and C(*)(3) also
      allowed us to reconstruct the g(EXAFS)(ij)(r,T) functions from EXAFS. Then, we
      made reverse Monte Carlo (RMC) simulations using the total structure factor S(K)
      obtained from synchrotron x-ray diffraction and the EXAFS oscillations chi(k) on
      the Se K edge as input data to obtain the g(RMC)(ij)(r) functions. Both methods
      furnished very similar g(ij)(r) functions, and the structural data obtained from
      them were also very similar. The results obtained from both methods showed the
      presence of Se-Te pairs indicating that there is alloying at the atomic level. In
      addition, we could not find any evidence of the presence of Te clusters in the
      alloy.

PMID- 22371433
TI  - Corneal thinning phenotypes: an alternative perspective.

PMID- 22371435
TI  - Differential regulation of MHC II and invariant chain expression during
      maturation of monocyte-derived dendritic cells.
AB  - DCs are potent initiators of adaptive immune responses toward invading pathogens.
      Upon reception of pathogenic stimuli, DCs initiate a complex differentiation
      program, culminating in mature DCs with an extreme capacity to activate naive T
      cells. During this maturation, DCs reduce the synthesis and turnover of MHC II
      molecules. This allows for a stable population of MHC II, presenting peptides
      captured at the time and place of activation, thus provoking specific immune
      responses toward the activating pathogen. The efficient loading of antigenic
      peptides onto MHC II is vitally dependent on the accessory molecule Ii, which
      aids in the assembly of the MHC II alpha- and beta-chains in the ER and directs
      their trafficking to the endocytic compartments, where they encounter endocytosed
      antigen. However, Ii plays additional roles in DC function by influencing
      migration, antigen uptake, and processing. To examine the biosynthetic background
      for diverse Ii functions in DCs, we investigated mRNA and protein levels of Ii
      compared with MHC II in human moDCs during maturation using various stimuli. We
      find that the production of Ii did not correlate with that of MHC II and that
      mature DCs maintain abundant levels of Ii despite a reduced production of new MHC
      II.

PMID- 22371436
TI  - A case of cellular alchemy: lineage reprogramming and its potential in
      regenerative medicine.
AB  - The field of regenerative medicine is rapidly gaining momentum as an increasing
      number of reports emerge concerning the induced conversions observed in cellular
      fate reprogramming. While in recent years, much attention has been focused on the
      conversion of fate-committed somatic cells to an embryonic-like or pluripotent
      state, there are still many limitations associated with the applications of
      induced pluripotent stem cell reprogramming, including relatively low
      reprogramming efficiency, the times required for the reprogramming event to take
      place, the epigenetic instability, and the tumorigenicity associated with the
      pluripotent state. On the other hand, lineage reprogramming involves the
      conversion from one mature cell type to another without undergoing conversion to
      an unstable intermediate. It provides an alternative approach in regenerative
      medicine that has a relatively lower risk of tumorigenesis and increased
      efficiency within specific cellular contexts. While lineage reprogramming
      provides exciting potential, there is still much to be assessed before this
      technology is ready to be applied in a clinical setting.

PMID- 22371437
TI  - The time to passage of biological and complex motion.
AB  - A significant part of human interactions occur with other human beings and not
      only with inanimate objects. It is important in everyday tasks to estimate the
      time it takes other people to reach (time to contact) or pass us (time to
      passage). Surprisingly, little is known about judging time to contact or time to
      passage of biological or other complex motions. In two experiments, rigid and non
      rigid (biological, inverted, scrambled, and complex non-biological) motion
      conditions were compared in a time-to-passage judgment task. Subjects could judge
      time to passage of point-light-walker displays. However, due to relative and
      opponent movements of body parts, all articulated patterns conveyed a noisier
      looming pattern. Non-rigid stimuli were judged as passing sooner than rigid
      stimuli but reflected more uncertainty in the judgments as revealed by precision
      judgments and required longer reaction times. Our findings suggested that
      perceptual judgments for complex motion, including biological patterns, are built
      on top of the same processing channels that are involved on rigid motion
      perception. The complexity of the motion pattern (rigid vs. non-rigid) plays a
      more determinant role than the "biologicity" of the stimulus (biological vs. non
      biological), at least concerning time-to-passage judgments.

PMID- 22371438
TI  - Characterization of the antigen specificity of T-cell clones from piperacillin
      hypersensitive patients with cystic fibrosis.
AB  - beta-Lactam antibiotics provide the cornerstone of treatment and reduce the rate
      of decline in lung function in patients with cystic fibrosis, but their use is
      limited by a high frequency of delayed-type allergic reactions. The objective of
      this study was to use cloned T-cells expressing a single T-cell receptor from
      five piperacillin-hypersensitive patients to characterize both the cellular
      pathophysiology of the reaction and antigen specificity to define the mechanism
      of activation of T-cells by piperacillin. More than 400 piperacillin-responsive
      CD4+, CD4+CD8+, or CD8+ T-cell clones were generated from lymphocyte
      transformation test and ELIspot-positive patients. The T-cell response
      (proliferation, T helper 2 cytokine secretion, and cytotoxicity) to piperacillin
      was concentration-dependent and highly specific. Enzyme-linked immunosorbent
      assay, gel electrophoresis, and mass spectrometry revealed that piperacillin
      bound exclusively to albumin in T-cell culture. Irreversible piperacillin binding
      at Lys 190, 195, 199, 432, and 541 on albumin and the stimulation of T-cells
      depended on incubation time. A synthetic piperacillin albumin conjugate
      stimulated T-cell receptors via a major histocompatibility complex- and
      processing-dependent pathway. Flucloxacillin competes for the same Lys residues
      on albumin as piperacillin, but the resulting conjugate does not stimulate T
      cells, indicating that binding of the beta-lactam hapten in peptide conjugates
      confers structural specificity on the activation of the T-cell receptors
      expressed on drug-specific clones. Collectively, these data describe the cellular
      processes that underlie the structural specificity of piperacillin antigen
      binding in hypersensitive patients with cystic fibrosis.

PMID- 22371439
TI  - Resistance profiles of emtricitabine and lamivudine in tenofovir-containing
      regimens.
AB  - OBJECTIVES: To compare the frequency of the selection of the M184V/I resistance
      mutation in HIV-infected patients who experienced virological failure while
      receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir
      disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted
      protease inhibitor (PI; lopinavir or atazanavir). METHODS: Patient data held at
      two clinical centres in France were analysed retrospectively. Eligible patients
      had experienced virological suppression (plasma HIV RNA <200 copies/mL) for >= 6
      months before experiencing their first virological failure (at least two
      measurements of plasma HIV RNA >= 200 copies/mL). RESULTS: Of the 880 patients
      eligible for the study, 278 patients had experienced virological failure while
      receiving FTC + TDF + ritonavir-boosted PI, 257 while receiving FTC + TDF + EFV,
      178 while receiving 3TC + TDF + EFV and 167 while receiving 3TC + TDF + ritonavir
      boosted PI. Proportions of patients harbouring the M184V/I mutation were 24% (n =
      62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF +
      EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC +
      TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted
      PI (P = 0.002; Fisher's exact test). The use of lamivudine versus emtricitabine
      (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir
      boosted PIs (P = 0.01) and the level of viral load at the time of virological
      failure (P = 0.01) were associated with selection of the M184V/I mutation
      (logistic regression analysis). CONCLUSIONS: Emtricitabine and lamivudine showed
      differing resistance profiles when administered in combination with tenofovir
      disproxil fumarate and either efavirenz or a ritonavir-boosted PI. The prevalence
      of the M184V/I resistance mutation was significantly lower in patients who
      received emtricitabine and tenofovir disoproxil fumarate than in those who
      received lamivudine and tenofovir disoproxil fumarate.

PMID- 22371440
TI  - Fluoroquinolone use and resistance of Gram-positive bacteria causing healthcare
      associated infections.

PMID- 22371441
TI  - Cardiovascular care in an increasingly diverse community.

PMID- 22371442
TI  - Sudden cardiac death caused by coronary heart disease.

PMID- 22371443
TI  - Digitalis intoxication induced by an acute accidental poisoning by lily of the
      valley.

PMID- 22371444
TI  - Phlegmasia cerulea dolens.

PMID- 22371445
TI  - Unruptured left coronary sinus of Valsalva aneurysm causing mitral valve
      obstruction.

PMID- 22371446
TI  - Near-complete obstruction of an aortic homograft.

PMID- 22371448
TI  - Letter by Gordon et al regarding article, "Pulmonary hypertension in heart
      failure with preserved ejection fraction: a target of phosphodiesterase-5
      inhibition in a 1-year study".

PMID- 22371449
TI  - Letter by Jamous regarding article, "Pulmonary hypertension in heart failure with
      preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1
      year study".

PMID- 22371450
TI  - Letter by Forfia and Borlaug regarding article, "Pulmonary hypertension in heart
      failure with preserved ejection fraction: a target of phosphodiesterase-5
      inhibition in a 1-year study".

PMID- 22371451
TI  - A phase I combination study of olaparib with cisplatin and gemcitabine in adults
      with solid tumors.
AB  - PURPOSE: To determine the safety and tolerability of olaparib with cisplatin and
      gemcitabine, establish the maximum tolerated dose (MTD), and evaluate the
      pharmacodynamic and pharmacokinetic profile of the combination. EXPERIMENTAL
      DESIGN: We conducted a phase I study of olaparib with cisplatin and gemcitabine
      in patients with advanced solid tumors. Treatment at dose level 1 (DL1) consisted
      of olaparib 100 mg orally every 12 hours on days 1 to 4, gemcitabine 500 mg/m(2)
      on days 3 and 10, and cisplatin 60 mg/m(2) on day 3. PAR levels were measured in
      peripheral blood mononuclear cells (PBMC). RESULTS: Dose-limiting toxicities
      (DLT) in two of three patients at DL1 included thrombocytopenia and febrile
      neutropenia. The protocol was amended to enroll patients treated with <= 2 prior
      severely myelosuppressive chemotherapy regimens and treated with olaparib 100 mg
      once daily on days 1 to 4 (DL-1). No DLTs were seen in six patients at DL-1.
      Because of persistent thrombocytopenia and neutropenia following a return to DL1,
      patients received 100 mg olaparib every 12 hours on day 1 only. No hematologic
      DLTs were observed; nonhematologic DLTs included gastrointestinal bleed, syncope,
      and hypoxia. Of 21 patients evaluable for response, two had partial response.
      Olaparib inhibited PARP in PBMCs and tumor tissue, although PAR levels were less
      effectively inhibited when olaparib was used for a short duration. CONCLUSIONS:
      Olaparib in combination with cisplatin and gemcitabine is associated with
      myelosuppression even at relatively low doses. Modified schedules of olaparib in
      chemotherapy naive patients will have to be explored with standard doses of
      chemotherapy.

PMID- 22371452
TI  - Expression of Epstein-Barr virus-encoded proteins in extranodal NK/T-cell
      Lymphoma, nasal type (ENKL): differences in biologic and clinical behaviors of
      LMP1-positive and -negative ENKL.
AB  - PURPOSE: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is closely associated
      with Epstein-Barr virus (EBV). To elucidate its pathogenetic role, we examined
      the expression profiles of EBV-encoded proteins, especially focusing on latent
      membrane protein 1 (LMP1). EXPERIMENTAL DESIGN: Immunohistochemistry was carried
      out using clinical samples from ENKL cases, which were diagnosed between 1996 and
      2010 at our institution. We statistically assessed the correlation between LMP1
      positivity and the clinicopathologic data and further examined phosphorylation
      status of NF-kappaB RelA and Akt in ENKL cell lines. RESULTS: Most of the 30
      examined cases showed pleomorphic morphology, natural killer cell
      immunophenotype, and a localized disease. Immunohistochemistry detected EBERs,
      but not EBNA2, in all cases. LMP1 and LMP2A were positive in 22 (73.3%) and 12
      cases (40.0%), respectively. LMP1-positive cases tended to show a localized
      disease (P = 0.060, the Fisher exact test). Nuclear localization of
      phosphorylated RelA and detection of phosphorylated Akt were predominantly
      observed in LMP1-positive cases (P = 0.002 and P < 0.001, respectively, the
      Fisher exact test). RNA silencing experiments of LMP1 in Hank1 cells suggested a
      positive correlation between LMP1 expression and phosphorylation of RelA and Akt.
      With a median follow-up period of 26.7 months (range, 0.2-142.3 months), the 2.5
      year overall survival rates for LMP1-positive and -negative cases were estimated
      at 78.3% and 12.5%, respectively (P = 0.001, log-rank test). CONCLUSIONS: LMP1
      expression shows correlations with phosphorylation of RelA and Akt and possibly
      has a favorable impact on clinical outcome in ENKL.

PMID- 22371453
TI  - A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of
      the head and neck.
AB  - PURPOSE: This study sought to determine the efficacy and safety profile of
      lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the
      head and neck (SCCHN). EXPERIMENTAL DESIGN: This phase II multiinstitutional
      study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those
      without (arm A) and those with (arm B) before exposure to an epidermal growth
      factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500
      mg daily. Primary endpoints were response rate (arm A) and progression-free
      survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and
      survival pathways were assessed in paired tumor biopsies obtained before and
      after therapy. RESULTS: Forty-five patients were enrolled, 27 in arm A and 18 in
      arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients.
      Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1
      vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial
      responses were observed, and stable disease was the best response observed in 41%
      of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects
      (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median
      OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B,
      respectively. Correlative analyses revealed an absence of EGFR inhibition in
      tumor tissue. CONCLUSION: Lapatinib as a single agent in recurrent/metastatic
      SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor
      naive or refractory subjects.

PMID- 22371454
TI  - Biomarkers for EGFR-antagonist response: in the genes and on the genes!
AB  - Patients with non-small cell lung carcinoma containing epidermal growth factor
      receptor (EGFR)-activating mutations benefit from EGFR-antagonist therapy. EGFR
      antagonist sensitivity is also correlated with epithelial-mesenchymal transition,
      which Walter and colleagues show to be marked by DNA-methylation changes. If
      validated, these markers could help identify patients with wild-type EGFR who
      will benefit from EGFR therapy.

PMID- 22371456
TI  - Discomfort and pain in newborns with myelomeningocele: a prospective evaluation.
AB  - OBJECTIVE: In a worldwide debate on deliberately terminating the lives of
      newborns, proponents point at newborns with very severe forms of myelomeningocele
      (MMC) and their assumed suffering, claiming there are no effective means of
      alleviating their distress. Nevertheless, the degree of discomfort and pain in
      these newborns has never been assessed in a structured manner. METHODS: In a
      prospective cohort study, 28 consecutive newborns with MMC were included over a 5
      year period and were followed up throughout their hospital stay for initial
      treatment. We created 2 disease severity groups on the basis of the Lorber
      criteria. The primary outcomes were discomfort and pain, assessed by
      simultaneously scoring 2 validated scales: the visual analog scale for pain and
      the Comfort Behavioral Scale for discomfort. These scores were coupled to a
      validated and evidence-based analgesia algorithm. RESULTS: Overall, discomfort
      related to pain was measured in 3.3% of the scores. This percentage differed
      little between the preoperative and postoperative periods and did not
      significantly differ between newborns with less severe MMC and severe MMC (3.9%
      vs 2.8%; P = .3). The mean dosage of paracetamol was 35 mg/kg per day (95%
      confidence interval: 32-39); the mean dosage of morphine was 0.9 MUg/kg per hour
      (95% confidence interval: 0.6 -1.2). CONCLUSION: Over the length of their
      hospital stays for initial treatment, all newborns with MMC presented with low
      levels of discomfort and pain independent of disease severity and time frame.

PMID- 22371455
TI  - Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion
      in an orthotopic mouse model and in epithelioid pleural mesothelioma patients.
AB  - PURPOSE: Mesothelin (MSLN) is a tumor-associated antigen, being investigated as a
      biomarker and therapeutic target in malignant pleural mesothelioma (MPM). The
      biologic function of MSLN overexpression in MPM is unknown. We hypothesized that
      MSLN may promote tumor invasion in MPM, a tumor characterized primarily by
      regional aggressiveness and rare distant metastases. EXPERIMENTAL DESIGN: Human
      and murine MPM cells with MSLN forced expression and short hairpin RNA knockdown
      were examined for proliferation, invasion, and matrix metalloproteinase (MMP)
      secretion. The influence of MSLN overexpression on MPM cell invasion was assessed
      in an orthotopic mouse model and in patient samples. RESULTS: MSLN expression
      promotes MPM cell invasion and MMP secretion in both human and murine MPM cells.
      In an orthotopic MPM mouse model characterized by our laboratory, MPM cells with
      MSLN overexpression preferentially localized to the tumor invading edge,
      colocalized with MMP-9 expression, and promoted decreased survival without an
      increase in tumor burden progression. In a tissue microarray from epithelioid MPM
      patients (n = 139, 729 cores), MSLN overexpression correlated with higher MMP-9
      expression at individual core level. Among stage III MPM patients (n = 72), high
      MSLN expression was observed in 26% of T2 tumors and 51% of T3 tumors.
      CONCLUSIONS: Our data provide evidence elucidating a biologic role for MSLN as a
      factor promoting tumor invasion and MMP-9 expression in MSLN expressing MPM. As
      regional invasion is the characteristic feature in MSLN expressing solid cancers
      (MPM, pancreas, and ovarian), our observations add rationale to studies
      investigating MSLN as a therapeutic target.

PMID- 22371457
TI  - Impact of an active video game on healthy children's physical activity.
AB  - OBJECTIVE: This naturalistic study tests whether children receiving a new (to
      them) active video game spontaneously engage in more physical activity than those
      receiving an inactive video game, and whether the effect would be greater among
      children in unsafe neighborhoods, who might not be allowed to play outside.
      METHODS: Participants were children 9 to 12 years of age, with a BMI >50th
      percentile, but <99th percentile; none of these children a medical condition that
      would preclude physical activity or playing video games. A randomized clinical
      trial assigned children to receiving 2 active or 2 inactive video games, the
      peripherals necessary to run the games, and a Wii console. Physical activity was
      monitored by using accelerometers for 5 weeks over the course of a 13-week
      experiment. Neighborhood safety was assessed with a 12 item validated
      questionnaire. RESULTS: There was no evidence that children receiving the active
      video games were more active in general, or at anytime, than children receiving
      the inactive video games. The outcomes were not moderated by parent perceived
      neighborhood safety, child BMI z score, or other demographic characteristics.
      CONCLUSIONS: These results provide no reason to believe that simply acquiring an
      active video game under naturalistic circumstances provides a public health
      benefit to children.

PMID- 22371458
TI  - Professionalism in practice: strategies for assessment, remediation, and
      promotion.

PMID- 22371459
TI  - Changing epidemiology of bacteremia in infants aged 1 week to 3 months.
AB  - BACKGROUND: Bacteremia in young infants has remained an important ongoing concern
      for decades. Despite changes in prenatal screening and infant immunizations, the
      current epidemiology of this problem has received little attention. METHODS: We
      conducted a retrospective analysis of all blood cultures collected at Kaiser
      Permanente Northern California on full-term, previously healthy infants
      presenting for care between 1 week to 3 months of age for whom a blood culture
      was drawn from January 1, 2005, through December 31, 2009. RESULTS: During the
      study period, 4255 blood cultures were collected from 160 818 full-term infants.
      Only 2% of all blood cultures were positive for pathogens (93/4255), whereas 247
      positive cultures were due to contaminants. The incidence rate of true bacteremia
      was 0.57 in 1000 full-term births. The most common pathogen was Escherichia coli
      (56%). Ninety-eight percent of infants with E coli bacteremia had a urinary tract
      infection. Group B Streptococcus and Staphylococcus aureus were the second and
      third most common pathogens, respectively. There were no cases of Listeria
      monocytogenes bacteremia or meningococcemia and only 1 case of enterococcal
      bacteremia. Ampicillin resistant pathogens accounted for 36% of organisms.
      CONCLUSIONS: Our study indicates bacteremia in young infants occurs infrequently
      and in only 2.2% of those who had a blood culture drawn. On the basis of the
      epidemiology of pathogens found in this large cohort, these data suggest a change
      in currently recommended presumptive antibiotic coverage in 1-week to 3-month-old
      infants with suspected bacteremia.

PMID- 22371460
TI  - HPV vaccine recommendations.
AB  - On October 25, 2011, the Advisory Committee on Immunization Practices of the
      Centers for Disease Control and Prevention recommended that the quadrivalent
      human papillomavirus vaccine (Gardasil; Merck & Co, Inc, Whitehouse Station, NJ)
      be used routinely in males. The American Academy of Pediatrics has reviewed
      updated data provided by the Advisory Committee on Immunization Practices on
      vaccine efficacy, safety, and cost-effectiveness as well as programmatic
      considerations and supports this recommendation. This revised statement updates
      recommendations for human papillomavirus immunization of both males and females.

PMID- 22371461
TI  - Functional difficulties and health conditions among children with special health
      needs.
AB  - OBJECTIVES: To describe the functional difficulties of children with special
      health needs and to demonstrate the shared and unique contributions in predicting
      health outcomes and informing therapeutic interventions, policies, and research
      by using data from the 2005-2006 National Survey of Children With Special Health
      Care Needs. RESULTS: Children with special health care needs experience an array
      of health conditions and functional difficulties that are interrelated. Although
      health conditions tend not to change, the characteristics of functional
      difficulties are subject to changes over time with age or as a result of
      interventions. Descriptive data highlight common functional difficulties across
      health conditions. Multiple regression analyses support both health conditions
      and functional difficulties predicting (1) health services, such as emergency
      department visits, (2) personal limitations such as impairment of daily
      activities and school absences, and (3) family impact, stopping or reducing work.
      Functional difficulties were, however, the stronger predictor for all outcomes
      except school absences. CONCLUSIONS: The results support the utility of expanding
      measures of children with special health care needs to include functional
      difficulties in survey research, as well as clinical and public health practice.
      Systematic inclusion of functional difficulties will inform policy development,
      program planning, outcome assessment, and resource allocation for this vulnerable
      population. A focus on functional difficulties facilitates stronger coordination
      of services across sectors including physical health, mental health, education,
      and other social services to improve the health and well-being for these children
      and youth.

PMID- 22371463
TI  - Moving toward better measures.

PMID- 22371464
TI  - What the Orphan Drug Act has done lately for children with rare diseases: a 10
      year analysis.
AB  - OBJECTIVES: The 1983 US Orphan Drug Act (ODA) provided incentives to stimulate
      treatment product development for patients with rare disease. This article
      highlights a decade of ODA contributions to this goal for children with RDs.
      METHODS: An internal US Food and Drug Administration database was the information
      source for orphan designations, marketing approvals, and prevalence numbers for
      2000 to 2009. Product categorization was based on the disease age of onset for
      which they received designation. Category 1 products were for diseases with onset
      exclusively in Childhood; Category 2 products were for diseases with onset at any
      age; and Category 3 products were for diseases with adult onset only. Disease
      prevalence distributions were analyzed by using population intervals of 20 000.
      RESULTS: From 2000 to 2009, 1138 orphan drugs were designated and 148 received
      marketing approval, of which 38 (26%) were for pediatric diseases. The proportion
      of approvals for pediatric products increased from 17.5% (10 of 57) in the first
      half of the decade, to 30.8% (28 of 91) in the second. More products received
      designation and marketing approval for pediatric diseases with prevalence numbers
      fewer than 20 000 than for any other prevalence subgroup. The median disease
      prevalence for all pediatric orphan designations that received marketing approval
      was 8972. Among the pediatric orphan drug approvals categorized by therapeutic
      class, the endocrine/metabolic drugs had the largest representation (39%).
      CONCLUSIONS: The ODA incentives have led to increased product availability for
      RDs overall, with an increasing number of marketing approvals for children this
      past decade.

PMID- 22371467
TI  - Stability of cognitive outcome from 2 to 5 years of age in very low birth weight
      children.
AB  - OBJECTIVES: This study assessed the stability of cognitive outcomes of premature,
      very low birth weight (VLBW; <=1500 g) children. METHODS: A regional cohort of
      120 VLBW children born between 2001 and 2004 was followed up by using the Bayley
      Scales of Infant Development, Second Edition, at 2 years of corrected age and the
      Wechsler Preschool and Primary Scale of Intelligence-Revised at the age of 5
      years. The Mental Development Index (MDI) and the full-scale IQ (FSIQ) were
      measured, respectively. A total of 168 randomly selected healthy term control
      children born in the same hospital were assessed for MDI and FSIQ. RESULTS: In
      the VLBW group, mean +/- SD MDI was 101.2 +/- 16.3 (range: 50-128), mean FSIQ was
      99.3 +/- 17.7 (range: 39-132), and the correlation between MDI and FSIQ was 0.563
      (P < .0001). In the term group, mean MDI was 109.8 +/- 11.7 (range: 54-128), mean
      FSIQ was 111.7 +/- 14.5 (range: 73-150), and the correlation between MDI and FSIQ
      was 0.400 (P < .0001). Overall, 83% of those VLBW children who had significant
      delay (-2 SD or less) according to MDI had it also in FSIQ. Similarly, 87% of
      those children who were in the average range in MDI were within the average range
      in FSIQ as well. CONCLUSIONS: Good stability of cognitive development over time
      was found in VLBW children and in term children between the ages of 2 and 5
      years. This conclusion stresses the value and clinical significance of early
      assessment at 2 years of corrected age. However, we also emphasize the importance
      of a long-term follow-up covering a detailed neuropsychological profile of these
      at-risk children.

PMID- 22371469
TI  - The python's embrace: clinical research regulation by institutional review
      boards.

PMID- 22371468
TI  - Baseball and softball.
AB  - Baseball and softball are among the most popular and safest sports in which
      children and adolescents participate. Nevertheless, traumatic and overuse
      injuries occur regularly, including occasional catastrophic injury and even
      death. Safety of the athlete is a constant focus of attention among those
      responsible for modifying rules. Understanding the stresses placed on the arm,
      especially while pitching, led to the institution of rules controlling the
      quantity of pitches thrown in youth baseball and established rest periods between
      pitching assignments. Similarly, field maintenance and awareness of environmental
      conditions as well as equipment maintenance and creative prevention strategies
      are critically important in minimizing the risk of injury. This statement serves
      as a basis for encouraging safe participation in baseball and softball. This
      statement has been endorsed by the Canadian Paediatric Society.

PMID- 22371462
TI  - Enrollment of extremely low birth weight infants in a clinical research study may
      not be representative.
AB  - BACKGROUND AND OBJECTIVE: The Surfactant Positive Airway Pressure and Pulse
      Oximetry Randomized Trial (SUPPORT) antenatal consent study demonstrated that
      mothers of infants enrolled in the SUPPORT trial had significantly different
      demographics and exposure to antenatal steroids compared with mothers of
      eligible, but not enrolled infants. The objective of this analysis was to compare
      the outcomes of bronchopulmonary dysplasia, severe retinopathy of prematurity,
      severe intraventricular hemorrhage or periventricular leukomalacia (IVH/PVL),
      death, and death/severe IVH/PVL for infants enrolled in SUPPORT in comparison
      with eligible, but not enrolled infants. METHODS: Perinatal characteristics and
      neonatal outcomes were compared for enrolled and eligible but not enrolled
      infants in bivariate analyses. Models were created to test the effect of
      enrollment in SUPPORT on outcomes, controlling for perinatal characteristics.
      RESULTS: There were 1316 infants enrolled in SUPPORT; 3053 infants were eligible,
      but not enrolled. In unadjusted analyses, enrolled infants had significantly
      lower rates of death before discharge, severe IVH/PVL, death/severe IVH/PVL (all
      < 0.001), and bronchopulmonary dysplasia (P = .003) in comparison with eligible,
      but not enrolled infants. The rate of severe retinopathy of prematurity was not
      significantly different. After adjustment for perinatal factors, enrollment in
      the trial was not a significant predictor of any of the tested clinical outcomes.
      CONCLUSIONS: The results of this analysis demonstrate significant outcome
      differences between enrolled and eligible but not enrolled infants in a trial
      using antenatal consent, which were likely due to enrollment bias resulting from
      the antenatal consent process. Additional research and regulatory review need to
      be conducted to ensure that large moderate-risk trials that require antenatal
      consent can be conducted in such a way as to ensure the generalizability of
      results.

PMID- 22371470
TI  - Self-referral and serious illness in children with fever.
AB  - OBJECTIVE: The goal of this study was to evaluate parents' capability to assess
      their febrile child's severity of illness and decision to present to the
      emergency department. We compared children referred by a general practitioner
      (GP) with those self-referred on the basis of illness-severity markers. METHODS:
      This was a cross-sectional observational study conducted at the emergency
      departments of a university and a teaching hospital. GP-referred or self-referred
      children with fever (aged <16 years) who presented to the emergency department
      (2006-2008) were included. Markers for severity of illness were urgency according
      to the Manchester Triage System, diagnostic interventions, therapeutic
      interventions, and follow-up. Associations between markers and referral type were
      assessed by using logistic regression analysis. Subgroup analyses were performed
      for patients with the most common presenting problems that accompanied the fever
      (ie, dyspnea, gastrointestinal complaints, neurologic symptoms, fever without
      specific symptoms). RESULTS: Thirty-eight percent of 4609 children were referred
      by their GP and 62% were self-referred. GP-referred children were classified as
      high urgency (immediate/very urgent categories) in 46% of the cases and self
      referrals in 45%. Forty-three percent of GP referrals versus 27% of self
      referrals needed extensive diagnostic intervention, intravenous
      medication/aerosol treatment, hospitalization, or a combination of these (odds
      ratio: 2.0 [95% confidence interval: 1.75-2.27]). In all subgroups, high urgency
      was not associated with referral type. GP-referred and self-referred children
      with dyspnea had similar frequencies of illness-severity markers. CONCLUSIONS:
      Although febrile self-referred children were less severely ill than GP-referred
      children, many parents properly judged and acted on the severity of their child's
      illness. To avoid delayed or missed diagnoses, recommendations regarding
      interventions that would discourage self-referral to the emergency department
      should be reconsidered.

PMID- 22371471
TI  - Breastfeeding and the use of human milk.
AB  - Breastfeeding and human milk are the normative standards for infant feeding and
      nutrition. Given the documented short- and long-term medical and
      neurodevelopmental advantages of breastfeeding, infant nutrition should be
      considered a public health issue and not only a lifestyle choice. The American
      Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for
      about 6 months, followed by continued breastfeeding as complementary foods are
      introduced, with continuation of breastfeeding for 1 year or longer as mutually
      desired by mother and infant. Medical contraindications to breastfeeding are
      rare. Infant growth should be monitored with the World Health Organization (WHO)
      Growth Curve Standards to avoid mislabeling infants as underweight or failing to
      thrive. Hospital routines to encourage and support the initiation and sustaining
      of exclusive breastfeeding should be based on the American Academy of Pediatrics
      endorsed WHO/UNICEF "Ten Steps to Successful Breastfeeding." National strategies
      supported by the US Surgeon General's Call to Action, the Centers for Disease
      Control and Prevention, and The Joint Commission are involved to facilitate
      breastfeeding practices in US hospitals and communities. Pediatricians play a
      critical role in their practices and communities as advocates of breastfeeding
      and thus should be knowledgeable about the health risks of not breastfeeding, the
      economic benefits to society of breastfeeding, and the techniques for managing
      and supporting the breastfeeding dyad. The "Business Case for Breastfeeding"
      details how mothers can maintain lactation in the workplace and the benefits to
      employers who facilitate this practice.

PMID- 22371472
TI  - Purinergic neuromuscular transmission is absent in the colon of P2Y(1) knocked
      out mice.
AB  - Purinergic and nitrergic co-transmission is the dominant mechanism responsible
      for neural-mediated smooth muscle relaxation in the gastrointestinal tract. The
      aim of the present paper was to test whether or not P2Y(1) receptors are involved
      in purinergic neurotransmission using P2Y(1)(-/-) knock-out mice. Tension and
      microelectrode recordings were performed on colonic strips. In wild type (WT)
      animals, electrical field stimulation (EFS) caused an inhibitory junction
      potential (IJP) that consisted of a fast IJP (MRS2500 sensitive, 1 MUm) followed
      by a sustained IJP (N(omega)-nitro-L-arginine (L-NNA) sensitive, 1 mm). The fast
      component of the IJP was absent in P2Y(1)(-/-) mice whereas the sustained IJP (L
      NNA sensitive) was recorded. In WT animals, EFS-induced inhibition of spontaneous
      motility was blocked by the consecutive addition of L-NNA and MRS2500. In P2Y(1)(
      /-) mice, EFS responses were completely blocked by L-NNA. In WT and P2Y(1)(-/-)
      animals, L-NNA induced a smooth muscle depolarization but 'spontaneous' IJP
      (MRS2500 sensitive) could be recorded in WT but not in P2Y(1)(-/-) animals.
      Finally, in WT animals, 1 MUm MRS2365 caused a smooth muscle hyperpolarization
      that was blocked by 1 MUm MRS2500. In contrast, 1 MUm MRS2365 did not modify
      smooth muscle resting membrane potential in P2Y(1)(-/-) mice. beta-Nicotinamide
      adenine dinucleotide (beta-NAD, 1 mm) partially mimicked the effect of MRS2365.
      We conclude that P2Y(1) receptors mediate purinergic neurotransmission in the
      gastrointestinal tract and beta-NAD partially fulfils the criteria to participate
      in rodent purinergic neurotransmission. The P2Y(1)(-/-) mouse is a useful animal
      model to study the selective loss of purinergic neurotransmission.

PMID- 22371473
TI  - Excitatory inputs to four types of spinocerebellar tract neurons in the cat and
      the rat thoraco-lumbar spinal cord.
AB  - The cerebellum receives information from the hindlimbs through several
      populations of spinocerebellar tract neurons. Although the role of these neurons
      has been established in electrophysiological experiments, the relative
      contribution of afferent fibres and central neurons to their excitatory input has
      only been estimated approximately so far. Taking advantage of differences in the
      immunohistochemistry of glutamatergic terminals of peripheral afferents and of
      central neurons (with vesicular glutamate transporters VGLUT1 or VGLUT2,
      respectively), we compared sources of excitatory input to four populations of
      spinocerebellar neurons in the thoraco-lumbar spinal cord: dorsal spinocerebellar
      tract neurons located in Clarke's column (ccDSCT) and in the dorsal horn (dhDSCT)
      and ventral spinocerebellar tract (VSCT) neurons including spinal border (SB)
      neurons. This was done on 22 electrophysiologically identified intracellularly
      labelled neurons in cats and on 80 neurons labelled by retrograde transport of
      cholera toxin b subunit injected into the cerebellum of rats. In both species
      distribution of antibodies against VGLUT1 and VGLUT2 on SB neurons (which have
      dominating inhibitory input from limb muscles), revealed very few VGLUT1 contacts
      and remarkably high numbers of VGLUT2 contacts. In VSCT neurons with excitatory
      afferent input, the number of VGLUT1 contacts was relatively high although VGLUT2
      contacts likewise dominated, while the proportions of VGLUT1 and VGLUT2
      immunoreactive terminals were the reverse on the two populations of DSCT neurons.
      These findings provide morphological evidence that SB neurons principally receive
      excitatory inputs from central neurons and provide the cerebellum with
      information regarding central neuronal activity.

PMID- 22371474
TI  - Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4
      dopamine receptors in rat brain slices.
AB  - Dopamine depletion in experimental models of Parkinson's disease promotes burst
      firing of neurons in the subthalamic nucleus (STN) and substantia nigra zona
      reticulata (SNR). A synaptically generated form of burst firing has been shown to
      arise from complex excitatory postsynaptic currents (EPSCs) that are evoked in
      SNR neurons by STN stimulation. The present experiments were designed to
      characterize actions of dopamine on complex EPSCs in slices of rat brain. Using
      patch pipettes to record whole-cell currents under voltage clamp, dopamine (30
      MUm) caused a reversible 64% reduction in complex EPSC charge. This effect was
      partially mimicked by D(2), D(3) and D(4) receptor agonists, and the action of
      dopamine could be nearly completely blocked by the combined effects of the D(2/3)
      antagonist sulpiride and the D(4) antagonist L-745,870. Local application of
      dopamine to the STN caused a larger inhibition of the complex EPSC (55%
      reduction) than did dopamine application to the SNR (15% reduction). Simple,
      monophasic EPSCs, which were evoked in SNR neurons by stimulating the SNR close
      to the recording pipette, were inhibited to a smaller extent compared to complex
      EPSCs. Bursts of action potentials evoked in SNR neurons by STN stimulation were
      inhibited by dopamine to a greater extent than was spontaneous firing. These
      results show that dopamine D(2)-like receptors inhibit complex EPSCs and burst
      discharges in the SNR by acting within the STN to suppress transmission in the
      subthalamonigral pathway. Dopamine receptor-mediated inhibition of polysynaptic
      connections in the STN might be beneficial in the treatment of Parkinson's
      disease.

PMID- 22371475
TI  - Opioid-related (ORL1) receptors are enriched in a subpopulation of sensory
      neurons and prolonged activation produces no functional loss of surface N-type
      calcium channels.
AB  - The opioid-related receptor, ORL1, is activated by the neuropeptide
      nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage-activated (HVA) calcium
      channel currents (I(Ca)) via a G-protein-coupled mechanism. Endocytosis of ORL1
      receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage
      gated calcium channel (VGCC) internalization via physical interaction between
      ORL1 and the N-type channel. However, there is no direct electrophysiological
      evidence for this mechanism in dorsal root ganglion (DRG) neurons or their
      central nerve terminals. The present study tested this using whole-cell patch
      clamp recordings of HVA I(Ca) in rat DRG neurons and primary afferent excitatory
      synaptic currents (eEPSCs) in spinal cord slices. DRG neurons were classified on
      the basis of diameter, isolectin-B4 (IB4) binding and responses to capsaicin,
      N/OFQ and a MU-opioid agonist, DAMGO. IB4-negative neurons less than 20 MUm
      diameter were selectively responsive to N/OFQ as well as DAMGO. In these neurons,
      ORL1 desensitization by a supramaximal concentration of N/OFQ was not followed by
      a decrease in HVA I(Ca) current density or proportion of whole-cell HVA I(Ca)
      contributed by N-type VGCC as determined using the N-type channel selective
      blocker, omega-conotoxin CVID. There was also no decrease in the proportion of N
      type I(Ca) when neurons were incubated at 37 degrees C with N/OFQ for 30 min
      prior to recording. In spinal cord slices, N/OFQ consistently inhibited eEPSCs
      onto dorsal horn neurons. As observed in DRG neurons, preincubation of slices in
      N/OFQ for 30 min produced no decrease in the proportion of eEPSCs inhibited by
      CVID. In conclusion, no internalization of the N-type VGCC occurs in either the
      soma or central nerve terminals of DRG neurons following prolonged exposure to
      high, desensitizing concentrations of N/OFQ.

PMID- 22371476
TI  - P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine
      colonic excitability and transit.
AB  - Activation of enteric inhibitory motor neurons causes inhibitory junctional
      potentials (IJPs) and muscle relaxation in mammalian gastrointestinal (GI)
      muscles, including humans. IJPs in many GI muscles are bi-phasic with a fast
      initial hyperpolarization (fIJP) due to release of a purine neurotransmitter and
      a slower hyperpolarization component (sIJP) due to release of nitric oxide. We
      sought to characterize the nature of the post-junctional receptor(s) involved in
      transducing purinergic neural inputs in the murine colon using mice with
      genetically deactivated P2ry1. Wild-type mice had characteristic biphasic IJPs
      and pharmacological dissection confirmed that the fIJP was purinergic and the
      sIJP was nitrergic. The fIJP was completely absent in P2ry1(-/-) mice and the
      P2Y1 receptor antagonist MRS2500 had no effect on electrical activity or
      responses to electrical field stimulation of intrinsic nerves in these mice.
      Contractile experiments confirmed that purinergic responses were abolished in
      P2ry1(-/-) mice. Picospritzing of neurotransmitter candidates (ATP and its
      primary metabolite, ADP) and beta-NAD (and its primary metabolite, ADP-ribose,
      ADPR) caused transient hyperpolarization responses in wild-type colons, but
      responses to beta-NAD and ADPR were completely abolished in P2ry1(-/-) mice.
      Hyperpolarization and relaxation responses to ATP and ADP were retained in colons
      of P2ry1(-/-) mice. Video imaging revealed that transit of fecal pellets was
      significantly delayed in colons from P2ry1(-/-) mice. These data demonstrate the
      importance of purinergic neurotransmission in regulating colonic motility and
      confirm pharmacological experiments suggesting that purinergic neurotransmission
      is mediated via P2Y1 receptors.

PMID- 22371477
TI  - Myenteric neurons of the mouse small intestine undergo significant
      electrophysiological and morphological changes during postnatal development.
AB  - Organized motility patterns in the gut depend on circuitry within the enteric
      nervous system (ENS), but little is known about the development of
      electrophysiological properties and synapses within the ENS. We examined the
      electrophysiology and morphology of myenteric neurons in the mouse duodenum at
      three developmental stages: postnatal day (P)0, P10-11, and adult. Like adults,
      two main classes of neurons could be identified at P0 and P10-11 based on
      morphology: neurons with multiple long processes that projected circumferentially
      (Dogiel type II morphology) and neurons with a single long process. However,
      postnatal Dogiel type II neurons differed in several electrophysiological
      properties from adult Dogiel type II neurons. P0 and P10-11 Dogiel type II
      neurons exhibited very prominent Ca(2+)-mediated after depolarizing potentials
      (ADPs) following action potentials compared to adult neurons. Adult Dogiel type
      II neurons are characterized by the presence of a prolonged after hyperpolarizing
      potential (AHP), but AHPs were very rarely observed at P0. The projection lengths
      of the long processes of Dogiel type II neurons were mature by P10-11. Uniaxonal
      neurons in adults typically have fast excitatory postsynaptic potentials (fEPSPs,
      'S-type' electrophysiology) mainly mediated by nicotinic receptors. Nicotinic
      fEPSPs were also recorded from neurons with a single long process at P0 and P10
      11. However, these neurons underwent major developmental changes in morphology,
      from predominantly filamentous neurites at birth to lamellar dendrites in mature
      mice. Unlike Dogiel type II neurons, the projection lengths of neurons with a
      single long process matured after P10-11. Slow EPSPs were rarely observed in
      P0/P10-11 neurons. This work shows that, although functional synapses are present
      and two classes of neurons can be distinguished electrophysiologically and
      morphologically at P0, major changes in electrophysiological properties and
      morphology occur during the postnatal development of the ENS.

PMID- 22371478
TI  - A method for detecting molecular transport within the cerebral ventricles of live
      zebrafish (Danio rerio) larvae.
AB  - The production and flow of cerebrospinal fluid performs an important role in the
      development and homeostasis of the central nervous system.However, these
      processes are difficult to study in the mammalian brain because the ventricles
      are situated deep within the parenchyma.In this communication we introduce the
      zebrafish larva as an in vivo model for studying cerebral ventricle and blood
      brain barrier function. Using confocal microscopy we show that zebrafish
      ventricles are topologically similar to those of the mammalian brain.We describe
      a new method for measuring the dynamics of molecular transport within the
      ventricles of live zebrafish by means of the uncaging of a fluorescein
      derivative. Furthermore, we determine that in 5-6 days post-fertilization
      zebrafish, the dispersal of molecules in the ventricles is driven by a
      combination of ciliary motion and diffusion. The zebrafish presents a tractable
      system with the advantage of genetics, size and transparency for exploring
      ventricular physiology and for mounting large-scale high throughput experiments.

PMID- 22371479
TI  - Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3
      pyramidal neurons in rat auditory cortex.
AB  - Associative Hebbian-type synaptic plasticity underlies the mechanisms of learning
      and memory; however, Hebbian learning rules lead to runaway dynamics of synaptic
      weights and lack mechanisms for synaptic competition.Heterosynaptic plasticity
      may solve these problems by complementing plasticity at synapses that were active
      during the induction, with opposite-sign changes at non-activated synapses. In
      visual cortex, a potential candidate mechanism for normalization is plasticity
      induced by a purely postsynaptic protocol, intracellular tetanization. Here we
      asked if intracellular tetanization can induce long-term plasticity in auditory
      cortex. We recorded excitatory postsynaptic potentials (EPSPs) of regular (n =76)
      and all-or-none (n =24) type in layer 2/3 pyramidal cells in slices from rat
      auditory cortex. After intracellular tetanization, 32 of 76 regular inputs (42%)
      showed long-term depression, 21 inputs (28%) showed potentiation and 23 inputs
      (30%) did not change. The direction of plasticity correlated with the initial
      release probability: inputs with initially low release probability tended to be
      potentiated, while inputs with high release probability tended to be depressed.
      Thus, intracellular tetanization had a normalizing effect on synaptic efficacy.
      Induction of plasticity by intracellular tetanization required a rise of
      intracellular [Ca(2+)], because it was impaired by chelating intracellular
      calcium with EGTA. The long-term changes induced by intracellular tetanization
      involved both pre and postsynaptic mechanisms. EPSP amplitude changes were
      correlated with changes of release indices: paired-pulse ratio and the inverse of
      the coefficient of variation (CV(-2)). Furthermore at some all-or-none synapses,
      changes of averaged response amplitude were correlated with a change of the
      failure rate, without a change of the synaptic potency, measured as averaged
      amplitude of successful responses. Presynaptic components of plastic changes were
      abolished in experiments with blockade of NO-synthesis and spread, indicating
      involvement of NO signalling. These results demonstrate that the ability of
      purely postsynaptic challenges to induce plasticity is a general property of
      pyramidal neurons of both auditory and visual cortices.

PMID- 22371480
TI  - In vivo patch-clamp recording from locus coeruleus neurones in the rat brainstem.
AB  - Locus coeruleus (LC) neurones extend noradrenergic projections throughout the
      neuroaxis and are involved in homeostatic functions such as pain modulation,
      arousal and cardio-respiratory control. To address the cellular mechanisms
      underlying pain modulation we have developed a patch-clamp recording technique
      from LC neurones in anaesthetized rats. These recordings showed LC discharge in
      vivo to be driven by both spontaneous membrane potential oscillations and CNQX
      sensitive EPSCs opposed by bicuculine-sensitive IPSCs. Hindlimb pinch evoked a
      biphasic action potential response underpinned by a slow monophasic excitatory
      current. This approach allows detailed characterisation of the synaptic and
      integrative mechanisms of LC responses to naturalistic stimulation.

PMID- 22371482
TI  - Closing the gaps in pediatric laboratory reference intervals: a CALIPER database
      of 40 biochemical markers in a healthy and multiethnic population of children.
AB  - BACKGROUND: Pediatric healthcare is critically dependent on the availability of
      accurate and precise laboratory biomarkers of pediatric disease, and on the
      availability of reference intervals to allow appropriate clinical interpretation.
      The development and growth of children profoundly influence normal circulating
      concentrations of biochemical markers and thus the respective reference
      intervals. There are currently substantial gaps in our knowledge of the
      influences of age, sex, and ethnicity on reference intervals. We report a
      comprehensive covariate-stratified reference interval database established from a
      healthy, nonhospitalized, and multiethnic pediatric population. METHODS: Healthy
      children and adolescents (n = 2188, newborn to 18 years of age) were recruited
      from a multiethnic population with informed parental consent and were assessed
      from completed questionnaires and according to defined exclusion criteria. Whole
      blood samples were collected for establishing age- and sex-stratified reference
      intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids,
      proteins) on the Abbott ARCHITECT c8000 analyzer. RESULTS: Reference intervals
      were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East
      Asians, and South Asian participants were evaluated with respect to the influence
      of ethnicity, and statistically significant differences were observed for 7
      specific biomarkers. CONCLUSIONS: The establishment of a new comprehensive
      database of pediatric reference intervals is part of the Canadian Laboratory
      Initiative in Pediatric Reference Intervals (CALIPER). It should assist
      laboratorians and pediatricians in interpreting test results more accurately and
      thereby lead to improved diagnosis of childhood diseases and reduced patient
      risk. The database will also be of global benefit once reference intervals are
      validated in transference studies with other analytical platforms and local
      populations, as recommended by the CLSI.

PMID- 22371481
TI  - Embryonic assembly of auditory circuits: spiral ganglion and brainstem.
AB  - During early development, peripheral sensory systems generate physiological
      activity prior to exposure to normal environmental stimuli. This activity is
      thought to facilitate maturation of these neurons and their connections, perhaps
      even promoting efficacy or modifying downstream circuitry. In the mammalian
      auditory system, initial connections form at embryonic ages, but the functional
      characteristics of these early neural connections have not been assayed. We
      investigated processes of embryonic auditory development using a whole-head slice
      preparation that preserved connectivity between peripheral and brainstem stations
      of the auditory pathway. Transgenic mice expressing fluorescent protein provided
      observation of spiral ganglion and cochlear nucleus neurons to facilitate
      targeted electrophysiological recording. Here we demonstrate an apparent
      peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire
      action potential-generating capacity at embryonic day 14 (E14), the earliest age
      tested, and action potential waveforms begin to mature in advance of comparable
      states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of
      the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are
      functional at E15, prior to VCN connectivity with the MNTB, which occurs at least
      1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14
      and are able to drive third-order auditory brainstem neurons by E17. This
      activity precedes cochlear-generated wave activity by 4 days and ear canal
      opening by at least 2 weeks. Together, these findings reveal a previously unknown
      initial developmental phase for auditory maturation, and further implicate the
      spiral ganglion as a potential controlling centre in this process.

PMID- 22371483
TI  - Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell
      cycle inhibitor p21(cip) (CDKN1A).
AB  - The TFAP2C transcription factor has been shown to downregulate transcription of
      the universal cell cycle inhibitor p21(cip) (CDKN1A). In examining the mechanism
      of TFAP2C-mediated repression, we have identified a ternary complex at the
      proximal promoter containing TFAP2C, the oncoprotein Myc, and the trimethylated
      lysine 4 of histone H3 (H3K4me3) demethylase, KDM5B. We demonstrated that while
      TFAP2C and Myc can downregulate the CDKN1A promoter independently, KDM5B acts as
      a corepressor dependent on the other two proteins. All three factors collaborate
      for optimal CDKN1A repression, which requires the AP-2 binding site at -111/-103
      and KDM5B demethylase activity. Silencing of TFAP2C-KDM5B-Myc led to increased
      H3K4me3 at the endogenous promoter and full induction of CDKN1A expression.
      Coimmunoprecipitation assays showed that TFAP2C and Myc associate with distinct
      domains of KDM5B and the TFAP2C C-terminal 270 amino acids (aa) are required for
      Myc and KDM5B interaction. Overexpression of all three proteins resulted in
      forced S-phase entry and attenuation of checkpoint activation, even in the
      presence of chemotherapy drugs. Since each protein has been linked to poor
      prognosis in breast cancer, our findings suggest that the TFAP2C-Myc-KDM5B
      complex promotes cell cycle progression via direct CDKN1A repression, thereby
      contributing to tumorigenesis and therapy failure.

PMID- 22371486
TI  - Viruses and interactomes in translation.
AB  - A decade of high-throughput screenings for intraviral and virus-host protein
      protein interactions led to the accumulation of data and to the development of
      theories on laws governing interactome organization for many viruses. We present
      here a computational analysis of intraviral protein networks (EBV, FLUAV, HCV,
      HSV-1, KSHV, SARS-CoV, VACV, and VZV) and virus-host protein networks (DENV, EBV,
      FLUAV, HCV, and VACV) from up-to-date interaction data, using various
      mathematical approaches. If intraviral networks seem to behave similarly, they
      are clearly different from the human interactome. Viral proteins target highly
      central human proteins, which are precisely the Achilles' heel of the human
      interactome. The intrinsic structural disorder is a distinctive feature of viral
      hubs in virus-host interactomes. Overlaps between virus-host data sets identify a
      core of human proteins involved in the cellular response to viral infection and
      in the viral capacity to hijack the cell machinery for viral replication. Host
      proteins that are strongly targeted by a virus seem to be particularly attractive
      for other viruses. Such protein-protein interaction networks and their analysis
      represent a powerful resource from a therapeutic perspective.

PMID- 22371484
TI  - A transcriptional regulatory role of the THAP11-HCF-1 complex in colon cancer
      cell function.
AB  - The recently identified Thanatos-associated protein (THAP) domain is an atypical
      zinc finger motif with sequence-specific DNA-binding activity. Emerging data
      suggest that THAP proteins may function in chromatin-dependent processes,
      including transcriptional regulation, but the roles of most THAP proteins in
      normal and aberrant cellular processes remain largely unknown. In this work, we
      identify THAP11 as a transcriptional regulator differentially expressed in human
      colon cancer. Immunohistochemical analysis of human colon cancers revealed
      increased THAP11 expression in both primary tumors and metastases. Knockdown of
      THAP11 in SW620 colon cancer cells resulted in a significant decrease in cell
      proliferation, and profiling of gene expression in these cells identified a novel
      gene set composed of 80 differentially expressed genes, 70% of which were
      derepressed by THAP11 knockdown. THAP11 was found to associate physically with
      the transcriptional coregulator HCF-1 (host cell factor 1) and recruit HCF-1 to
      target promoters. Importantly, THAP11-mediated gene regulation and its chromatin
      association require HCF-1, while HCF-1 recruitment at these genes requires
      THAP11. Collectively, these data provide the first characterization of THAP11
      dependent gene expression in human colon cancer cells and suggest that the THAP11
      HCF-1 complex may be an important transcriptional and cell growth regulator in
      human colon cancer.

PMID- 22371487
TI  - The role of chaperone-subunit usher domain interactions in the mechanism of
      bacterial pilus biogenesis revealed by ESI-MS.
AB  - The PapC usher is a beta-barrel outer membrane protein essential for assembly and
      secretion of P pili that are required for adhesion of pathogenic E. coli, which
      cause the development of pyelonephritis. Multiple protein subunits form the P
      pilus, the highly specific assembly of which is coordinated by the usher. Despite
      a wealth of structural knowledge, how the usher catalyzes subunit polymerization
      and orchestrates a correct and functional order of subunit assembly remain
      unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal
      (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone
      subunit (PapDPapX) complexes is investigated using noncovalent electrospray
      ionization mass spectrometry. The results reveal that each usher domain is able
      to bind all six PapDPapX complexes, consistent with an active role of all three
      usher domains in pilus biogenesis. Using collision induced dissociation, combined
      with competition binding experiments and dissection of the adhesin subunit, PapG,
      into separate pilin and adhesin domains, the results reveal why PapG has a
      uniquely high affinity for the usher, which is consistent with this subunit
      always being displayed at the pilus tip. In addition, we show how the different
      soluble usher domains cooperate to coordinate and control efficient pilus
      assembly at the usher platform. As well as providing new information about the
      protein-protein interactions that determine pilus biogenesis, the results
      highlight the power of noncovalent MS to interrogate biological mechanisms,
      especially in complex mixtures of species.

PMID- 22371488
TI  - Urine proteome analysis reflects atherosclerotic disease in an ApoE-/- mouse
      model and allows the discovery of new candidate biomarkers in mouse and human
      atherosclerosis.
AB  - Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted
      but remains elusive. However, a previous polymarker or pattern approach of urine
      polypeptides in humans reflected coronary artery disease with high accuracy. The
      aim of the current study is to use urine proteomics in ApoE(-/-) mice to discover
      proteins with pathophysiological roles in atherogenesis and to identify urinary
      polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE(-/
      ) mice either on high fat diet (HFD) or chow diet was collected over 12 weeks;
      urine of wild type mice on HFD was used to exclude diet-related proteome changes.
      Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples
      identified 16 polypeptides specific for ApoE(-/-) mice on HFD. In a blinded test
      set, these polypeptides allowed identification of atherosclerosis at a
      sensitivity of 90% and specificity of 100%, as well as monitoring of disease
      progression. Sequencing of the discovered polypeptides identified fragments of
      alpha(1)-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated
      protein, and collagen. Using immunohistochemistry, alpha(1)-antitrypsin, EGF, and
      collagen type I were shown to be highly expressed in atherosclerotic plaques of
      ApoE(-/-) mice on HFD. Urinary excretion levels of collagen and alpha(1)
      antitrypsin fragments also significantly correlated with intraplaque collagen and
      alpha(1)-antitrypsin content, mirroring plaque protein expression in the urine
      proteome. To provide further confirmation that the newly identified proteins are
      relevant in humans, the presence of collagen type I, alpha(1)-antitrypsin, and
      EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis
      in mice exemplifies the potential of a novel multimarker approach for the
      noninvasive detection of atherosclerosis and monitoring of disease progression.
      Furthermore, this approach represents a novel discovery tool for the
      identification of proteins relevant in murine and human atherosclerosis and thus
      also defines potential novel therapeutic targets.

PMID- 22371490
TI  - Defective retinal depolarizing bipolar cells in regulators of G protein signaling
      (RGS) 7 and 11 double null mice.
AB  - Two members of the R7 subfamily of regulators of G protein signaling, RGS7 and
      RGS11, are present at dendritic tips of retinal depolarizing bipolar cells
      (DBCs). Their involvement in the mGluR6/Galpha(o)/TRPM1 pathway that mediates DBC
      light responses has been implicated. However, previous genetic studies employed
      an RGS7 mutant mouse that is hypomorphic, and hence the exact role of RGS7 in
      DBCs remains unclear. We have made a true RGS7-null mouse line with exons 6-8
      deleted. The RGS7(-/-) mouse is viable and fertile but smaller in body size.
      Electroretinogram (ERG) b-wave implicit time in young RGS7(-/-) mice is prolonged
      at eye opening, but the phenotype disappears at 2 months of age. Expression
      levels of RGS6 and RGS11 are unchanged in RGS7(-/-) retina, but the Gbeta5S level
      is significantly reduced. By characterizing a complete RGS7 and RGS11 double
      knock-out (711dKO) mouse line, we found that Gbeta5S expression in the retinal
      outer plexiform layer is eliminated, as is the ERG b-wave. Ultrastructural
      defects akin to those of Gbeta5(-/-) mice are evident in 711dKO mice. In retinas
      of mice lacking RGS6, RGS7, and RGS11, Gbeta5S is undetectable, whereas levels of
      the photoreceptor-specific Gbeta5L remain unchanged. Whereas RGS6 alone sustains
      a significant amount of Gbeta5S expression in retina, the DBC-related defects in
      Gbeta5(-/-) mice are caused solely by a combined loss of RGS7 and RGS11. Our data
      support the notion that the role of Gbeta5 in the retina, and likely in the
      entire nervous system, is mediated exclusively by R7 RGS proteins.

PMID- 22371489
TI  - Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase
      acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate.
AB  - Peroxin 5 (PEX5), the peroxisomal protein shuttling receptor, binds newly
      synthesized peroxisomal matrix proteins in the cytosol and promotes their
      translocation across the organelle membrane. During the translocation step, PEX5
      itself becomes inserted into the peroxisomal docking/translocation machinery.
      PEX5 is then monoubiquitinated at a conserved cysteine residue and extracted back
      into the cytosol in an ATP-dependent manner. We have previously shown that the
      ubiquitin-PEX5 thioester conjugate (Ub-PEX5) released into the cytosol can be
      efficiently disrupted by physiological concentrations of glutathione, raising the
      possibility that a fraction of Ub-PEX5 is nonenzymatically deubiquitinated in
      vivo. However, data suggesting that Ub-PEX5 is also a target of a deubiquitinase
      were also obtained in that work. Here, we used an unbiased biochemical approach
      to identify this enzyme. Our results suggest that ubiquitin-specific protease 9X
      (USP9X) is by far the most active deubiquitinase acting on Ub-PEX5, both in
      female rat liver and HeLa cells. We also show that USP9X is an elongated
      monomeric protein with the capacity to hydrolyze thioester, isopeptide, and
      peptide bonds. The strategy described here will be useful in identifying
      deubiquitinases acting on other ubiquitin conjugates.

PMID- 22371491
TI  - Identification and profiling of novel alpha1A-adrenoceptor-CXC chemokine receptor
      2 heteromer.
AB  - We have provided the first evidence for specific heteromerization between the
      alpha(1A)-adrenoceptor (alpha(1A)AR) and CXC chemokine receptor 2 (CXCR2) in live
      cells. alpha(1A)AR and CXCR2 are both expressed in areas such as the stromal
      smooth muscle layer of the prostate. By utilizing the G protein-coupled receptor
      (GPCR) heteromer identification technology on the live cell-based bioluminescence
      resonance energy transfer (BRET) assay platform, our studies in human embryonic
      kidney 293 cells have identified norepinephrine-dependent beta-arrestin
      recruitment that was in turn dependent upon co-expression of alpha(1A)AR with
      CXCR2. These findings have been supported by co-localization observed using
      confocal microscopy. This norepinephrine-dependent beta-arrestin recruitment was
      inhibited not only by the alpha(1)AR antagonist Terazosin but also by the CXCR2
      specific allosteric inverse agonist SB265610. Furthermore, Labetalol, which is
      marketed for hypertension as a nonselective beta-adrenoceptor antagonist with
      alpha(1)AR antagonist properties, was identified as a heteromer-specific-biased
      agonist exhibiting partial agonism for inositol phosphate production but
      essentially full agonism for beta-arrestin recruitment at the alpha(1A)AR-CXCR2
      heteromer. Finally, bioluminescence resonance energy transfer studies with both
      receptors tagged suggest that alpha(1A)AR-CXCR2 heteromerization occurs
      constitutively and is not modulated by ligand. These findings support the concept
      of GPCR heteromer complexes exhibiting distinct pharmacology, thereby providing
      additional mechanisms through which GPCRs can potentially achieve their diverse
      biological functions. This has important implications for the use and future
      development of pharmaceuticals targeting these receptors.

PMID- 22371493
TI  - Novel phenol-soluble modulin derivatives in community-associated methicillin
      resistant Staphylococcus aureus identified through imaging mass spectrometry.
AB  - Staphylococcus aureus causes a wide range of human disease ranging from localized
      skin and soft tissue infections to potentially lethal systemic infections. S.
      aureus has the biosynthetic ability to generate numerous virulence factors that
      assist in circumventing the innate immune system during disease pathogenesis.
      Recent studies have uncovered a set of extracellular peptides produced by
      community-associated methicillin-resistant S. aureus (CA-MRSA) with homology to
      the phenol-soluble modulins (PSMs) from Staphylococcus epidermidis. CA-MRSA PSMs
      contribute to skin infection and recruit and lyse neutrophils, and truncated
      versions of these peptides possess antimicrobial activity. In this study, novel
      CA-MRSA PSM derivatives were discovered by the use of microbial imaging mass
      spectrometry. The novel PSM derivatives are compared with their parent full
      length peptides for changes in hemolytic, cytolytic, and neutrophil-stimulating
      activity. A potential contribution of the major S. aureus secreted protease
      aureolysin in processing PSMs is demonstrated. Finally, we show that PSM
      processing occurs in multiple CA-MRSA strains by structural confirmation of
      additional novel derivatives. This work demonstrates that IMS can serve as a
      useful tool to go beyond genome predictions and expand our understanding of the
      important family of small peptide virulence factors.

PMID- 22371492
TI  - Structural characterization and oligomerization of the TssL protein, a component
      shared by bacterial type VI and type IVb secretion systems.
AB  - The Type VI secretion system (T6SS) is a macromolecular system distributed in
      Gram-negative bacteria, responsible for the secretion of effector proteins into
      target cells. The T6SS has a broad versatility as it can target both eukaryotic
      and prokaryotic cells. It is therefore involved in host pathogenesis or killing
      neighboring bacterial cells to colonize a new niche. At the architecture level,
      the T6SS core apparatus is composed of 13 proteins, which assemble in two
      subcomplexes. One of these subcomplexes, composed of subunits that share
      structural similarities with bacteriophage tail and baseplate components, is
      anchored to the cell envelope by the membrane subcomplex. This latter is
      constituted of at least three proteins, TssL, TssM, and TssJ. The crystal
      structure of the TssJ outer membrane lipoprotein and its interaction with the
      inner membrane TssM protein have been recently reported. TssL and TssM share
      sequence homology and characteristics with two components of the Type IVb
      secretion system (T4bSS), IcmH/DotU and IcmF, respectively. In this study, we
      report the crystal structure of the cytoplasmic domain of the TssL inner membrane
      protein from the enteroaggregative Escherichia coli Sci-1 T6SS. It folds as a
      hook-like structure composed of two three-helix bundles. Two TssL molecules
      associate to form a functional complex. Although the TssL trans-membrane segment
      is the main determinant of self-interaction, contacts between the cytoplasmic
      domains are required for TssL function. Based on sequence homology and secondary
      structure prediction, we propose that the TssL structure is the prototype for the
      members of the TssL and IcmH/DotU families.

PMID- 22371494
TI  - Contribution of residues in second transmembrane domain of ASIC1a protein to ion
      selectivity.
AB  - Acid-sensing ion channels (ASICs) are proton-gated cation-selective channels
      expressed in the peripheral and central nervous systems. The ion permeation
      pathway of ASIC1a is defined by residues 426-450 in the second transmembrane
      (TM2) segment. The gate, formed by the intersection of the TM2 segments,
      localizes near the extracellular boundary of the plasma membrane. We explored the
      contribution to ion permeation and selectivity of residues in the TM2 segment of
      ASIC1a. Studies of accessibility with positively charged methanethiosulfonate
      reagents suggest that the permeation pathway in the open state constricts below
      the gate, restricting the passage to large ions. Substitution of residues in the
      intracellular vestibule at positions 437, 438, 443, or 446 significantly
      increased the permeability to K(+) versus Na(+). ASIC1a shows a selectivity
      sequence for alkali metals of Na(+)>Li(+)>K(+)?Rb(+)>Cs(+). Alanine and cysteine
      substitutions at position 438 increased, to different extents, the relative
      permeability to Li(+), K(+), Rb(+), and Cs(+). For these mutants, ion permeation
      was not a function of the diameter of the nonhydrated ion, suggesting that Gly
      438 encompasses an ion coordination site that is essential for ion selectivity.
      M437C and A443C mutants showed slightly increased permeability to K(+), Rb(+),
      and Cs(+), suggesting that substitutions at these positions influence ion
      discrimination by altering molecular sieving. Our results indicate that ion
      selectivity is accomplished by the contribution of multiple sites in the pore of
      ASIC1a.

PMID- 22371495
TI  - The RNA-binding protein RNPC1 stabilizes the mRNA encoding the RNA-binding
      protein HuR and cooperates with HuR to suppress cell proliferation.
AB  - The RNA-binding protein HuR, a member of the embryonic lethal abnormal vision/Hu
      protein family, plays a critical role in many cellular processes, including cell
      proliferation, angiogenesis, and inflammatory response. Despite significant
      progresses in understanding how HuR functions, the mechanism by which HuR
      expression is controlled is still poorly understood. Here, we showed that RNA
      binding protein RNPC1 post-transcriptionally regulates HuR expression via mRNA
      stability. Specifically, we showed that overexpression of RNPC1 increases,
      whereas knockdown or knock-out of RNPC1 decreases, the level of HuR transcript
      and protein. Moreover, we showed that RNPC1, but not mutant RNPC1 deficient in
      RNA binding, stabilizes HuR transcript via binding to its 3'-untranslated region.
      Furthermore, to determine the biological significance of RNPC1-enhanced HuR
      expression, we showed that HuR, by repressing c-Myc expression, facilitates RNPC1
      mediated growth suppression. Together, we have uncovered a novel mechanism by
      which HuR is regulated by RNPC1 via mRNA stability and HuR is a mediator of RNPC1
      induced growth suppression.

PMID- 22371496
TI  - Calmodulin kinase II constitutively binds, phosphorylates, and inhibits brush
      border Na+/H+ exchanger 3 (NHE3) by a NHERF2 protein-dependent process.
AB  - The epithelial brush border (BB) Na(+)/H(+) exchanger 3 (NHE3) accounts for most
      renal and intestinal Na(+) absorption. Ca(2+)/calmodulin-dependent protein kinase
      II (CaMKII) inhibits NHE3 activity under basal conditions in intact intestine,
      acting in the BB, but the mechanism is unclear. We now demonstrate that in both
      PS120 fibroblasts and polarized Caco-2BBe cells expressing NHE3, CaMKII inhibits
      basal NHE3 activity, because the CaMKII-specific inhibitors KN-93 and KN-62
      stimulate NHE3 activity. This inhibition requires NHERF2. CaMKIIgamma associates
      with NHE3 between aa 586 and 605 in the NHE3 C terminus in a Ca(2+)-dependent
      manner, with less association when Ca(2+) is increased. CaMKII inhibits NHE3 by
      an effect on its turnover number, not changing surface expression. Back
      phosphorylation demonstrated that NHE3 is phosphorylated by CaMKII under basal
      conditions. This overall phosphorylation of NHE3 is not affected by the presence
      of NHERF2. Amino acids downstream of NHE3 aa 690 are required for CaMKII to
      inhibit basal NHE3 activity, and mutations of the three putative CaMKII
      phosphorylation sites downstream of aa 690 each prevented KN-93 stimulation of
      NHE3 activity. These studies demonstrate that CaMKIIgamma is a novel NHE3-binding
      protein, and this association is reduced by elevated Ca(2+). CaMKII inhibits
      basal NHE3 activity associated with phosphorylation of NHE3 by effects requiring
      aa downstream of NHE3 aa 690 and of the CaMKII-binding site on NHE3. CaMKII
      binding to and phosphorylation of the NHE3 C terminus are parts of the
      physiologic regulation of NHE3 that occurs in fibroblasts as well as in the BB of
      an intestinal Na(+)-absorptive cell.

PMID- 22371497
TI  - beta-N-Acetylglucosamine (O-GlcNAc) is a novel regulator of mitosis-specific
      phosphorylations on histone H3.
AB  - O-Linked beta-N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational
      modification that cycles on and off serine and threonine residues of
      nucleocytoplasmic proteins. The O-GlcNAc modification shares a complex
      relationship with phosphorylation, as both modifications are capable of mutually
      inhibiting the occupation of each other on the same or nearby amino acid residue.
      In addition to diabetes, cancer, and neurodegenerative diseases, O-GlcNAc appears
      to play a significant role in cell growth and cell cycle progression, although
      the precise mechanisms are still not well understood. A recent study also found
      that all four core nucleosomal histones (H2A, H2B, H3, and H4) are modified with
      O-GlcNAc, although no specific sites on H3 were reported. Here, we describe that
      histone H3, a protein highly phosphorylated during mitosis, is modified with O
      GlcNAc. Several biochemical assays were used to validate that H3 is modified with
      O-GlcNAc. Mass spectrometry analysis identified threonine 32 as a novel O-GlcNAc
      site. O-GlcNAc was detected at higher levels on H3 during interphase than
      mitosis, which inversely correlated with phosphorylation. Furthermore, increased
      O-GlcNAcylation was observed to reduce mitosis-specific phosphorylation at serine
      10, serine 28, and threonine 32. Finally, inhibiting OGA, the enzyme responsible
      for removing O-GlcNAc, hindered the transition from G2 to M phase of the cell
      cycle, displaying a phenotype similar to preventing mitosis-specific
      phosphorylation on H3. Taken together, these data indicate that O-GlcNAcylation
      regulates mitosis-specific phosphorylations on H3, providing a mechanistic switch
      that orchestrates the G2-M transition of the cell cycle.

PMID- 22371498
TI  - Structural insights into antibody sequestering and neutralizing of Na+ channel
      alpha-type modulator from old world scorpion venom.
AB  - The Old World scorpion Androctonus australis hector (Aah) produces one of the
      most lethal venoms for humans. Peptidic alpha-toxins AahI to AahIV are
      responsible for its potency, with AahII accounting for half of it. All four
      toxins are high affinity blockers of the fast inactivation phase of mammalian
      voltage-activated Na(+) channels. However, the high antigenic polymorphism of
      alpha-toxins prevents production of a polyvalent neutralizing antiserum, whereas
      the determinants dictating their trapping by neutralizing antibodies remain
      elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab)
      with high affinity and selectivity for AahII and solved a 2.3 A-resolution
      crystal structure of the complex. Sequestering of the C-terminal region of the
      bound toxin within a groove formed by the Fab combining loops is associated with
      a toxin orientation and main and side chain conformations that dictate the AahII
      antigenic specificity and efficient neutralization. From an anti-AahI mAb, we
      also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 A
      resolution structure solved revealed a Fab molecule devoid of a bound AahI and
      with combining loops involved in packing interactions, denoting expulsion of the
      bound antigen upon crystal formation. Comparative analysis of the groove-like
      combining site of the toxin-bound anti-AahII Fab and planar combining surface of
      the unbound anti-AahI Fab along with complementary data from a flexible docking
      approach suggests occurrence of distinctive trapping orientations for the two
      toxins relative to their respective Fab. This study provides complementary
      templates for designing new molecules aimed at capturing Aah alpha-toxins and
      suitable for immunotherapy.

PMID- 22371499
TI  - O-GlcNAc transferase is involved in glucocorticoid receptor-mediated
      transrepression.
AB  - Recruitment of O-GlcNAc transferase (OGT) to promoters plays an important role in
      gene repression. Glucocorticoid signaling represses the transcriptional
      activities of NF-kappaB and AP-1 through direct binding, yet the molecular
      mechanisms remain to be elucidated. Here we report that OGT is an important
      component of GR-mediated transrepression. OGT associates with ligand-bound GR in
      a multi-protein repression complex. Overexpression of OGT potentiates the GR
      transrepression pathway, whereas depletion of endogenous OGT by RNA interference
      abolishes the repression. The recruitment of OGT by GR leads to increased O
      GlcNAcylation and decreased phosphorylation of RNA polymerase II on target genes.
      Functionally, overexpression of OGT enhances glucocorticoid-induced apoptosis in
      resistant cell lines while knockdown of OGT prevents sensitive cell lines from
      apoptosis. These studies identify a molecular mechanism of GR transrepression,
      and highlight the function of O-GlcNAc in hormone signaling.

PMID- 22371500
TI  - Steroid receptor coactivator-interacting protein (SIP) inhibits caspase
      independent apoptosis by preventing apoptosis-inducing factor (AIF) from being
      released from mitochondria.
AB  - Apoptosis-inducing factor (AIF) is a caspase-independent death effector. Normally
      residing in the mitochondrial intermembrane space, AIF is released and
      translocated to the nucleus in response to proapoptotic stimuli. Nuclear AIF
      binds to DNA and induces chromatin condensation and DNA fragmentation,
      characteristics of apoptosis. Until now, it remained to be clarified how the
      mitochondrial-nuclear translocation of AIF is regulated. Here we report that
      steroid receptor coactivator-interacting protein (SIP) interacts directly with
      AIF in mitochondria and specifically inhibits caspase-independent and AIF
      dependent apoptosis. Challenging cells with apoptotic stimuli leads to rapid
      degradation of SIP, and subsequently AIF is liberated from mitochondria and
      translocated to the nucleus to induce apoptosis. Together, our data demonstrate
      that SIP is a novel regulator in caspase-independent and AIF-mediated apoptosis.

PMID- 22371501
TI  - Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic
      fibroblast growth factor.
AB  - Basic fibroblast growth factor (bFGF) is a therapeutic target of anti
      angiogenesis. Here, we report that a novel sulfated glycopeptide derived from
      Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese
      medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly
      decreased the production of bFGF in hepatoma cells by suppressing early growth
      response-1. GSPP inhibited the release of bFGF from extracellular matrix by
      blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited
      bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly,
      GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial
      cells, whereas it had no inhibitory effect on endothelial cells in the absence of
      bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization
      and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model.
      These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF
      production, release from the extracellular matrix, and binding to its low
      affinity receptor, heparin/heparan sulfate.

PMID- 22371503
TI  - Structure of factor H-binding protein B (FhbB) of the periopathogen, Treponema
      denticola: insights into progression of periodontal disease.
AB  - Periodontitis is the most common disease of microbial etiology in humans.
      Periopathogen survival is dependent upon evasion of complement-mediated
      destruction. Treponema denticola, an important contributor to periodontitis,
      evades killing by the alternative complement cascade by binding factor H (FH) to
      its surface. Bound FH is rapidly cleaved by the T. denticola protease,
      dentilisin. In this report, the structure of the T. denticola FH-binding protein,
      FhbB, was solved to 1.7 A resolution. FhbB possesses a unique fold that imparts
      high thermostability. The kinetics of the FH/FhbB interaction were assessed using
      surface plasmon resonance. A K(D) value in the micromolar range (low affinity)
      was demonstrated, and rapid off kinetics were observed. Site-directed mutagenesis
      and sucrose octasulfate competition assays collectively indicate that the
      negatively charged face of FhbB binds within FH complement control protein module
      7. This study provides significant new insight into the molecular basis of
      FH/FhbB interaction and advances our understanding of the role that T. denticola
      plays in the development and progression of periodontal disease.

PMID- 22371502
TI  - Myocilin interacts with syntrophins and is member of dystrophin-associated
      protein complex.
AB  - Genetic studies have linked myocilin to open angle glaucoma, but the functions of
      the protein in the eye and other tissues have remained elusive. The purpose of
      this investigation was to elucidate myocilin function(s). We identified alpha1
      syntrophin, a component of the dystrophin-associated protein complex (DAPC), as a
      myocilin-binding candidate. Myocilin interacted with alpha1-syntrophin via its N
      terminal domain and co-immunoprecipitated with alpha1-syntrophin from C2C12
      myotubes and mouse skeletal muscle. Expression of 15-fold higher levels of
      myocilin in the muscles of transgenic mice led to the elevated association of
      alpha1-syntrophin, neuronal nitric-oxide synthase, and alpha-dystroglycan with
      DAPC, which increased the binding of laminin to alpha-dystroglycan and Akt
      signaling. Phosphorylation of Akt and Forkhead box O-class 3, key regulators of
      muscle size, was increased more than 3-fold, whereas the expression of muscle
      specific RING finger protein-1 and atrogin-1, muscle atrophy markers, was
      decreased by 79 and 88%, respectively, in the muscles of transgenic mice.
      Consequently, the average size of muscle fibers of the transgenic mice was
      increased by 36% relative to controls. We suggest that intracellular myocilin
      plays a role as a regulator of muscle hypertrophy pathways, acting through the
      components of DAPC.

PMID- 22371504
TI  - Structural basis for dual nucleotide selectivity of aminoglycoside 2''
      phosphotransferase IVa provides insight on determinants of nucleotide specificity
      of aminoglycoside kinases.
AB  - Enzymatic phosphorylation through a family of enzymes called aminoglycoside O
      phosphotransferases (APHs) is a major mechanism by which bacteria confer
      resistance to aminoglycoside antibiotics. Members of the APH(2") subfamily are of
      particular clinical interest because of their prevalence in pathogenic strains
      and their broad substrate spectra. APH(2") enzymes display differential
      preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2"
      phosphotransferase IVa (APH(2")-IVa) being a member that utilizes both
      nucleotides at comparable efficiencies. We report here four crystal structures of
      APH(2")-IVa, two of the wild type enzyme and two of single amino acid mutants,
      each in complex with either adenosine or guanosine. Together, these structures
      afford a detailed look at the nucleoside-binding site architecture for this
      enzyme and reveal key elements that confer dual nucleotide specificity, including
      a solvent network in the interior of the nucleoside-binding pocket and the
      conformation of an interdomain linker loop. Steady state kinetic studies, as well
      as sequence and structural comparisons with members of the APH(2") subfamily and
      other aminoglycoside kinases, rationalize the different substrate preferences for
      these enzymes. Finally, despite poor overall sequence similarity and structural
      homology, analysis of the nucleoside-binding pocket of APH(2")-IVa shows a
      striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also
      exhibits dual nucleotide specificity. These results, in complement with the
      multitude of existing inhibitors against CK2, can serve as a structural basis for
      the design of nucleotide-competitive inhibitors against clinically relevant APH
      enzymes.

PMID- 22371505
TI  - Arabidopsis vacuolar H+-ATPase (V-ATPase) B subunits are involved in actin
      cytoskeleton remodeling via binding to, bundling, and stabilizing F-actin.
AB  - Vacuolar H(+)-ATPase (V-ATPase) is a membrane-bound multisubunit enzyme complex
      composed of at least 14 different subunits. The complex regulates the
      physiological processes of a cell by controlling the acidic environment, which is
      necessary for certain activities and the interaction with the actin cytoskeleton
      through its B and C subunits in both humans and yeast. Arabidopsis V-ATPase has
      three B subunits (AtVAB1, AtVAB2, and AtVAB3), which share 97.27% sequence
      identity and have two potential actin-binding sites, indicating that these AtVABs
      may have crucial functions in actin cytoskeleton remodeling and plant cell
      development. However, their biochemical functions are poorly understood. In this
      study, we demonstrated that AtVABs bind to and co-localize with F-actin, bundle F
      actin to form higher order structures, and stabilize actin filaments in vitro. In
      addition, the AtVABs also show different degrees of activities in capping the
      barbed ends but no nucleating activities, and these activities were not regulated
      by calcium. The functional similarity and differences of the AtVABs implied that
      they may play cooperative and distinct roles in Arabidopsis cells.

PMID- 22371506
TI  - Low red/far-red ratios reduce Arabidopsis resistance to Botrytis cinerea and
      jasmonate responses via a COI1-JAZ10-dependent, salicylic acid-independent
      mechanism.
AB  - Light is an important modulator of plant immune responses. Here, we show that
      inactivation of the photoreceptor phytochrome B (phyB) by a low red/far-red ratio
      (R:FR), which is a signal of competition in plant canopies, down-regulates the
      expression of defense markers induced by the necrotrophic fungus Botrytis
      cinerea, including the genes that encode the transcription factor ETHYLENE
      RESPONSE FACTOR1 (ERF1) and the plant defensin PLANT DEFENSIN1.2 (PDF1.2). This
      effect of low R:FR correlated with a reduced sensitivity to jasmonate (JA), thus
      resembling the antagonistic effects of salicylic acid (SA) on JA responses. Low
      R:FR failed to depress PDF1.2 mRNA levels in a transgenic line in which PDF1.2
      transcription was up-regulated by constitutive expression of ERF1 in a coronatine
      insensitive1 (coi1) mutant background (35S::ERF1/coi1). These results suggest
      that the low R:FR effect, in contrast to the SA effect, requires a functional
      SCFCOI1-JASMONATE ZIM-DOMAIN (JAZ) JA receptor module. Furthermore, the effect of
      low R:FR depressing the JA response was conserved in mutants impaired in SA
      signaling (sid2-1 and npr1-1). Plant exposure to low R:FR ratios and the phyB
      mutation markedly increased plant susceptibility to B. cinerea; the effect of low
      R:FR was (1) independent of the activation of the shade-avoidance syndrome, (2)
      conserved in the sid2-1 and npr1-1 mutants, and (3) absent in two RNA
      interference lines disrupted for the expression of the JAZ10 gene. Collectively,
      our results suggest that low R:FR ratios depress Arabidopsis (Arabidopsis
      thaliana) immune responses against necrotrophic microorganisms via a SA
      independent mechanism that requires the JAZ10 transcriptional repressor and that
      this effect may increase plant susceptibility to fungal infection in dense
      canopies.

PMID- 22371508
TI  - The phosphatidylcholine diacylglycerol cholinephosphotransferase is required for
      efficient hydroxy fatty acid accumulation in transgenic Arabidopsis.
AB  - We previously identified an enzyme, phosphatidylcholine diacylglycerol
      cholinephosphotransferase (PDCT), that plays an important role in directing fatty
      acyl fluxes during triacylglycerol (TAG) biosynthesis. The PDCT mediates a
      symmetrical interconversion between phosphatidylcholine (PC) and diacylglycerol
      (DAG), thus enriching PC-modified fatty acids in the DAG pool prior to forming
      TAG. We show here that PDCT is required for the efficient metabolism of
      engineered hydroxy fatty acids in Arabidopsis (Arabidopsis thaliana) seeds. When
      a fatty acid hydroxylase (FAH12) from castor (Ricinus communis) was expressed in
      Arabidopsis seeds, the PDCT-deficient mutant accumulated only about half the
      amount of hydroxy fatty acids compared with that in the wild-type seeds. We also
      isolated a PDCT from castor encoded by the RcROD1 (Reduced Oleate Desaturation1)
      gene. Seed-specific coexpression of this enzyme significantly increased hydroxy
      fatty acid accumulation in wild type-FAH12 and in a previously produced
      transgenic Arabidopsis line coexpressing a castor diacylglycerol acyltransferase
      2. Analyzing the TAG molecular species and regiochemistry, along with analysis of
      fatty acid composition in TAG and PC during seed development, indicate that PDCT
      acts in planta to enhance the fluxes of fatty acids through PC and enrich the
      hydroxy fatty acids in DAG, and thus in TAG. In addition, PDCT partially restores
      the oil content that is decreased in FAH12-expressing seeds. Our results add a
      new gene in the genetic toolbox for efficiently engineering unusual fatty acids
      in transgenic oilseeds.

PMID- 22371509
TI  - Cases: "safety" technology: a hidden cause of diabetic ketoacidosis.

PMID- 22371507
TI  - Subclassification and biochemical analysis of plant papain-like cysteine
      proteases displays subfamily-specific characteristics.
AB  - Papain-like cysteine proteases (PLCPs) are a large class of proteolytic enzymes
      associated with development, immunity, and senescence. Although many properties
      have been described for individual proteases, the distribution of these
      characteristics has not been studied collectively. Here, we analyzed 723 plant
      PLCPs and classify them into nine subfamilies that are present throughout the
      plant kingdom. Analysis of these subfamilies revealed previously unreported
      distinct subfamily-specific functional and structural characteristics. For
      example, the NPIR and KDEL localization signals are distinctive for subfamilies,
      and the carboxyl-terminal granulin domain occurs in two PLCP subfamilies, in
      which some individual members probably evolved by deletion of the granulin
      domains. We also discovered a conserved double cysteine in the catalytic site of
      SAG12-like proteases and two subfamily-specific disulfides in RD19A-like
      proteases. Protease activity profiling of representatives of the PLCP subfamilies
      using novel fluorescent probes revealed striking polymorphic labeling profiles
      and remarkably distinct pH dependency. Competition assays with peptide-epoxide
      scanning libraries revealed common and unique inhibitory fingerprints. Finally,
      we expand the detection of PLCPs by identifying common and organ-specific
      protease activities and identify previously undetected proteases upon labeling
      with cell-penetrating probes in vivo. This study provides the plant protease
      research community with tools for further functional annotation of plant PLCPs.

PMID- 22371510
TI  - Bridging the dementia gap.

PMID- 22371511
TI  - Missing covariate data in clinical research: when and when not to use the missing
      indicator method for analysis.

PMID- 22371513
TI  - Provinces weighing HPV vaccination of boys.

PMID- 22371514
TI  - Separating hype from reality in the era of the affordable genome.

PMID- 22371515
TI  - Increased risk of cognitive and functional decline in patients with atrial
      fibrillation: results of the ONTARGET and TRANSCEND studies.
AB  - BACKGROUND: The role of atrial fibrillation in cognitive impairment and dementia,
      independent of stroke, is uncertain. We sought to determine the association of
      atrial fibrillation with cognitive and physical impairment in a large group of
      patients at high cardiovascular risk. METHODS: We conducted a post-hoc analysis
      of two randomized controlled trials involving 31,546 patients, the aims of which
      were to evaluate the efficacy of treatment with ramipril plus telmisartan
      (ONTARGET) or telmisartan alone (TRANSCEND) in reducing cardiovascular disease.
      We evaluated the cognitive function of participants at baseline and after two and
      five years using the Mini-Mental State Examination (MMSE). In addition, we
      recorded incident dementia, loss of independence in activities of daily living
      and admission to long-term care facilities. We used a Cox regression model
      adjusting for main confounders to determine the association between atrial
      fibrillation and our primary outcomes: a decrease of three or more points in MMSE
      score, incident dementia, loss of independence in performing activities of daily
      living and admission to long-term care. RESULTS: We enrolled 31,506 participants
      for whom complete information on atrial fibrillation was available, 70.4% of whom
      were men. The mean age of participants was 66.5 years, and the mean baseline MMSE
      score was 27.7 (standard deviation 2.9) points. At baseline, 1016 participants
      (3.3%) had atrial fibrillation, with the condition developing in an additional
      2052 participants (6.5%) during a median follow-up of 56 months. Atrial
      fibrillation was associated with an increased risk of cognitive decline (hazard
      ratio [HR] 1.14, 95% confidence interval [CI] 1.03-1.26), new dementia (HR 1.30,
      95% CI 1.14-1.49), loss of independence in performing activities of daily living
      (HR 1.35, 95% CI 1.19-1.54) and admission to long-term care facilities (HR 1.53,
      95% CI 1.31-1.79). Results were consistent among participants with and without
      stroke or receiving antihypertensive drugs. INTERPRETATION: Cognitive and
      functional decline are important consequences of atrial fibrillation, even in the
      absence of overt stroke.

PMID- 22371516
TI  - Scrofula, the king's evil.

PMID- 22371517
TI  - The adverse effects of brand-name drug prescribing.

PMID- 22371518
TI  - Lungs from donation after circulatory death donors: an alternative source to
      brain-dead donors? Midterm results at a single institution.
AB  - OBJECTIVES: Donor organ shortage remains to be the major limitation in lung
      transplantation, and donation after circulatory death (DCD) might represent one
      way to alleviate this problem. DCD was introduced to our institution in 2007 and
      has been a part of our clinical routine since then. Here, we present the mid-term
      results of lung transplantation from DCD in a single institution and compare the
      outcomes with the lung recipient cohort receiving lungs from donation after brain
      death (DBD). METHODS: Since initiation of the DCD programme in March 2007, of the
      157 lung transplantations performed, 26 (16.5%) were retrieved from DCD donors,
      with 25 double- and 1 single-lung transplants being performed. Results were
      compared with standard DBD transplantations. Analyses included, amongst others,
      donor characteristics, survival, prevalence of primary graft dysfunction, acute
      rejection, lung function tests during follow-up, onset of bronchiolitis
      obliterans syndrome (BOS) as well as duration of mechanical ventilation, hospital
      and intensive care unit length of stay. RESULTS: While there was no significant
      difference between lung function, BOS and survival between the two groups, lungs
      from DCD donors had a higher PaO(2) (median; interquartile range) 498.3 (451.5;
      525) vs. DBD 442.5 (371.25; 502) kPa before retrieval (P = 0.009). There was also
      a longer total ischaemic time in the DCD vs. DBD group: 320 min (298.75; 393.25)
      vs. 285.5 min (240; 373) (P = 0.025). All other parameters were comparable.
      CONCLUSIONS: Medium-term results after lung transplantation with organs procured
      after circulatory death are comparable with those obtained after standard lung
      transplantation. Therefore, DCD could be used to significantly increase the donor
      pool.

PMID- 22371519
TI  - Repair of stent graft-induced retrograde type A aortic dissection using the E
      vita open prosthesis.
AB  - OBJECTIVES: Stent graft-induced retrograde type A dissection is a life
      threatening complication after endovascular treatment of acute aortic type B
      dissections. METHODS: From August 2005 to February 2011, retrograde aortic
      dissection occurred in 4 of 29 patients (13.8%) undergoing thoracic endovascular
      aortic repair (TEVAR) for acute complicated aortic type B dissection. Three
      patients underwent emergent surgical conversion immediately after TEVAR. The
      operative strategy was a combined surgical and endovascular approach (frozen
      elephant trunk technique) using a specially designed hybrid prosthesis (Jotec E
      vita open). All operations were performed under moderate hypothermia (25-28
      degrees C) and selective bilateral antegrade cerebral perfusion. The mean
      duration of circulatory arrest was 56 +/- 7 min. Operative data and the outcome
      of surgery were analysed retrospectively. Data were analysed retrospectively in
      the limited number of patients. RESULTS: All patients survived the surgical
      procedure. No stroke, paraplegia, renal failure or other major complications
      occurred. Postoperative CT scans revealed perigraft thrombus formation and stable
      aortic dimensions in all patients after 6 months. In one patient, the retrograde
      dissection remained primarily undetected and untreated. The patient died
      suddenly, with no clinical signs, within 7 days after stent graft implantation.
      Autopsy revealed cardiac tamponade due to retrograde type A aortic dissection.
      CONCLUSIONS: Retrograde aortic dissection type A is a serious complication of
      thoracic endovascular repair of acute aortic type B dissection. Despite the small
      number of patients investigated in this study, the frozen elephant trunk
      technique appears to be a feasible bail-out strategy for the treatment of these
      acute aortic events.

PMID- 22371522
TI  - Isolated posteromedial papillary muscle endocarditis.

PMID- 22371521
TI  - Management of anastomotic leakage-induced tracheobronchial fistula following
      oesophagectomy: the role of endoscopic stent insertion.
AB  - OBJECTIVES: Tracheobronchial fistulas are rare but life-threatening complications
      after oesophagectomy. Leakage of the oesophagointestinal anastomosis with
      inflammatory involvement of the tracheobronchial tree is the predominant reason
      for postoperative fistulization between the airways and the oesophagus or the
      gastric tube. Successful management is challenging and still controversially
      discussed. After promising results in the treatment of intrathoracic anastomotic
      leaks, we adopted endoscopic stent implantation as the primary treatment option
      in patients with anastomotic leak-induced tracheobronchial fistula. The aim of
      this study was to investigate the feasibility, the limits and the results of this
      procedure. METHODS: Between January 2004 and December 2010, 222 consecutive
      patients underwent oesophageal resection mainly for oesophageal cancer. An
      anastomotic leak-induced tracheobronchial fistula was bronchoscopically verified
      in seven patients. Four patients received endoscopic implantation of either a
      self-expanding tracheal or oesophageal stent or both as primary treatment.
      Surgical re-exploration was mandatory in 2 patients because of necrosis of the
      pulled-up gastric tube or gangrene of the airways. One patient was conservatively
      managed. RESULTS: Endoscopic stent placement was successfully accomplished in all
      4 patients. Two patients received an oesophageal stent, one patient a tracheal
      stent and one patient both an oesophageal and a tracheal stent. Closure of the
      fistula was achieved in all cases and 3 patients finally recovered while one died
      by reason of respiratory failure. In both surgical re-explored patients resection
      of the gastric tube was performed, and in one patient, because of subtotal
      gangrene of the right bronchial tree, emergency pneumectomy was also mandatory.
      Both patients died due to severe sepsis and respiratory failure. The one
      conservatively treated patient died from severe pneumonia. CONCLUSIONS: Treatment
      of anastomotic leak-induced tracheobronchial fistulas by means of oesophageal and
      tracheal stent implantation is feasible. If stent insertion is limited by gastric
      tube necrosis or bronchial gangrene, the prognosis is likely to be fatal.

PMID- 22371523
TI  - Multiple stent fractures detected by multislice computed tomography after full
      metal jacket stents.

PMID- 22371524
TI  - Age-dependent changes in contractile function and passive elastic properties of
      myocardium from mice lacking muscle LIM protein (MLP).
AB  - AIMS: Muscle LIM protein (MLP) null mice are often used as a model for human
      dilated cardiomyopathy. So far, little is known about the time course and
      pathomechanisms leading to the development of the adult phenotype. METHODS AND
      RESULTS: We systematically analysed the contractile phenotype, myofilament
      calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, histology, and
      mRNA expression in mice aged 4 and 12 weeks. In 4-week-old animals, there was no
      significant difference in the force-frequency relationship (FFR) and
      catecholamine response of intact isolated papillary muscles between wild-type
      (WT) and MLP null myocardium. In 12-week-old animals, WT myocardium exhibited a
      significantly positive FFR, while that of MLP null mice was significantly
      negative, and the inotropic response to catecholamines was significantly reduced
      in MLP null mice. This time course of decline in contractile function was
      confirmed in vivo by echocardiography. Whereas at 4 weeks of age MLP null mice
      and WT littermates showed similar levels of SERCA2a (sarcoplasmic reticulum
      Ca(2+) ATPase) expression, the expression was significantly lower in 12-week-old
      MLP null mice compared with littermate controls. Myofilament Ca(2)(+)
      responsiveness was not affected by the lack of MLP, irrespective of age. Whereas
      in 4-week-old animals MLP null myocardium showed a trend to an increased
      compliance compared with the WT, myocardium of 12-week-old MLP null mice was
      significantly less compliant than WT myocardium. Parallel to the decrease in
      compliance there was an increase in fibrosis in the MLP null animals. CONCLUSION:
      Our data suggest that MLP deficiency does not primarily influence myocardial
      contractility. A lack of MLP leads to an age-dependent impairment of excitation
      contraction coupling with resulting contractile dysfunction and secondary
      fibrosis.

PMID- 22371525
TI  - Weight monitoring in patients with severe heart failure (WISH). A randomized
      controlled trial.
AB  - AIMS: This multicentre, randomized controlled trial hypothesized that daily
      electronic transmission of body weight to a heart failure (HF) clinic will reduce
      cardiac hospitalization in patients recently hospitalized with HF. METHODS AND
      RESULTS: A total of 344 patients were randomized to either an intervention group
      (IG) or a control group (CG). Of the 319 patients included in the final analysis,
      the mean age was 73 years (SD 10.2), 75% were males, and 57% had a left
      ventricular ejection fraction (LVEF) <30%. Patients in both groups were
      recommended to weigh themselves daily and, in the case of sudden weight gain >2
      kg in 3 days, to contact the HF clinic. Patients in the IG were given an
      electronic scale and the weight was automatically transmitted to and monitored at
      the HF clinic. No significant differences were found for the primary endpoint,
      cardiac re-hospitalization [70/153 CG, 70/166 IG; hazard ratio (HR) 0.90, 95%
      confidence interval (CI) 0.65-1.26, P = 0.54], or for the secondary endpoints,
      which included all-cause hospitalization (84/153 CG, 79/166 IG; HR 0.83, 95% CI
      0.61-1.13, P = 0.24), death from any cause (8/153 CG, 5/166 IG; HR 0.57, 95% CI
      0.19-1.73, P = 0.32), or the composite endpoint of cardiac hospitalization and
      death from any cause (78/153 CG, 75/166 IG; HR 0.90, 95% CI 0.65-1.26, P = 0.54).
      Subgroup analyses did not show any benefits for patients in the IG despite their
      more frequent monitoring; 398 occasions compared with 30 occasions in the CG.
      CONCLUSION: Daily electronic transmission of body weight and monitoring three
      times a week did not decrease hospitalization or death in HF patients followed up
      at a HF clinic.

PMID- 22371526
TI  - Detection of a RiataTM insulation failure by the Medtronic Lead Integrity
      AlertTM.
AB  - We describe a case of insulation failure in a Riata implantable cardioverter
      defibrillator lead [St Jude Medical (SJM), St Paul, MN, USA] detected by the Lead
      Integrity Alert (LIA)TM, without impedance changes. The Medtronic LIA may permit
      early detection of Riata lead failure.

PMID- 22371527
TI  - Assessment of circadian rhythms in humans: comparison of real-time fibroblast
      reporter imaging with plasma melatonin.
AB  - We compared the period of the rhythm of plasma melatonin, driven by the
      hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral
      fibroblasts to assess the effects on these rhythms of a polymorphism of PER3
      (rs57875989), which is associated with sleep timing. In vitro circadian period
      was determined using luminometry of cultured fibroblasts, in which the expression
      of firefly luciferase was driven by the promoter of the circadian gene Arntl
      (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced
      desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark
      cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61+/-0.33
      h, mean+/-SD) were longer than in vivo periods (31 participants, 24.16+/-0.17 h;
      P<0.0001) but did not differ between PER3 genotypes (P>0.4). Analyses of
      replicate in vitro assessments demonstrated that circadian period was
      reproducible within individuals (intraclass correlation=0.62), but in vivo and in
      vitro period assessments did not correlate (P>0.9). In accordance with circadian
      entrainment theory, in vivo period correlated with the timing of melatonin
      (P<0.05) at baseline and with diurnal preference (P<0.05). Individual circadian
      rhythms can be reliably assessed in fibroblasts but may not correlate with
      physiological rhythms driven by the central circadian pacemaker.

PMID- 22371528
TI  - Rho GTPases link cellular contractile force to the density and distribution of
      nanoscale adhesions.
AB  - The ability of cells to adhere and to exert contractile forces governs their
      capacity to move within an organism. The cytoskeletal regulators of the Rho
      GTPase proteins are involved in control of the contractile forces of cells. To
      elucidate the basis of cell migration, we analyzed contractile forces and
      nanoscale adhesion-related particles in single cells expressing constitutively
      active variants of Rho GTPases by using traction-force microscopy and ultra-high
      resolution stimulated emission depletion microscopy, respectively. RhoAV14
      induced large increases in the contractile forces of single cells, with Rac1L61
      and RhoDV26 having more moderate effects. The RhoAV14- and RhoDV26-induced forces
      showed similar spatial distributions and were accompanied by reduced or unaltered
      cell spreading. In contrast, the Rac1L61-induced force had different, scattered,
      force distributions that were linked to increased cell spreading. All three of
      these Rho GTPase activities caused a loss of thick stress fibers and focal
      adhesions and a more homogenous distribution of nanoscale adhesion-related
      particles over the ventral surface of the cells. Interestingly, only RhoAV14
      increased the density of these particles. Our data suggest a Rac1-specific mode
      for cells to generate contractile forces. Importantly, increased density and a
      more homogenous distribution of these small adhesion-related particles promote
      cellular contractile forces.

PMID- 22371529
TI  - DNA methylation in peripheral blood measured by LUMA is associated with breast
      cancer in a population-based study.
AB  - Our purpose was to identify epigenetic markers of breast cancer risk, which can
      be reliably measured in peripheral blood and are amenable for large population
      screening. We used 2 independent assays, luminometric methylation assay (LUMA)
      and long interspersed elements-1 (LINE-1) to measure "global methylation content"
      in peripheral blood DNA from a well-characterized population-based case-control
      study. We examined associations between methylation levels and breast cancer risk
      among 1055 cases and 1101 controls and potential influences of 1-carbon
      metabolism on global methylation. Compared with women in the lowest quintile of
      LUMA methylation, those in the highest quintile had a 2.41-fold increased risk of
      breast cancer (95% confidence interval: 1.83-3.16; P, trend<0.0001). The
      association did not vary by other key tumor characteristics and lifestyle risk
      factors. Consistent with LUMA findings, genome-wide methylation profiling of a
      subset of samples revealed greater promoter hypermethylation in breast cancer
      case participants (P=0.04); higher LUMA was associated with higher promoter
      methylation in the controls (P=0.05). LUMA levels were also associated with
      functional sodium nitroprusside in key 1-carbon metabolizing genes, MTHFR C677T
      (P=0.001) and MTRR A66G (P=0.018). LINE-1 methylation was associated with neither
      breast cancer risk nor 1-carbon metabolism. Our results show that global promoter
      hypermethylation measured in peripheral blood was associated with breast cancer
      risk.

PMID- 22371530
TI  - Vimentin phosphorylation by Cdc2 in Schwann cell controls axon growth via beta1
      integrin activation.
AB  - Although preconditioning injury on the peripheral nerve induces axonal
      regenerative capacity in neurons, it is not known whether similar lesion effects
      occur in glial cells. Here we demonstrate that Schwann cells are activated by
      peripheral nerve preinjury and primed to mediate axon regeneration. Cdc2, which
      was induced from Schwann cells after sciatic nerve injury, phosphorylated
      vimentin almost exclusively in the distal nerve area. Phospho-vimentin-positive
      Schwann cells showed increased migration activity and were in close contact with
      process outgrowth of co-cultured neurons. Vimentin phosphorylation by Cdc2 was
      involved in beta1-integrin activation leading to FAK phoshorylation and
      associated with Erk1/2 activation in Schwann cells. Neurite outgrowth of dorsal
      root ganglion neurons was increased by co-culture with activated Schwann cells,
      in which phospho-vimentin signaling was transmitted into beta1-integrin
      activation. Then neurite outgrowth was suppressed by genetic depletion of phospho
      vimentin and beta1 integrin as well as inhibition of vimentin phosphorylation by
      Cdc2 inhibitor purvalanol A. The sciatic nerve graft harboring activated Schwann
      cells into the spinal cord induced Schwann cell migration beyond the graft-host
      barrier and facilitated regeneration of spinal axons, which was inhibited by
      purvalanol A pretreatment of the graft. This is the first report to our knowledge
      demonstrating that activation of phospho-vimentin linked to beta1-integrin
      pathway may mediate transcellular signaling to promote axon growth.

PMID- 22371532
TI  - Arthroscopy of the hip for paediatric and adolescent disorders: current concepts.
AB  - Hip arthroscopy is particularly attractive in children as it confers advantages
      over arthrotomy or open surgery, such as shorter recovery time and earlier return
      to activity. Developments in surgical technique and arthroscopic instrumentation
      have enabled extension of arthroscopy of the hip to this age group. Potential
      challenges in paediatric and adolescent hip arthroscopy include variability in
      size, normal developmental change from childhood to adolescence, and conditions
      specific to children and adolescents and their various consequences. Treatable
      disorders include the sequelae of traumatic and sports-related hip joint
      injuries, Legg-Calve-Perthes' disease and slipped capital femoral epiphysis, and
      the arthritic and septic hip. Intra-articular abnormalities are rarely isolated
      and are often associated with underlying morphological changes. This review
      presents the current concepts of hip arthroscopy in the paediatric and adolescent
      patient, covering clinical assessment and investigation, indications and results
      of the experience to date, as well as technical challenges and future directions.

PMID- 22371533
TI  - Current controversies in hip surgery: a report on the proceedings of the London
      Hip Meeting 2011.
AB  - An international faculty of orthopaedic surgeons presented their work on the
      current challenges in hip surgery at the London Hip Meeting which was attended by
      over  400 delegates. The topics covered included femoroacetabular impingement,
      thromboembolic phenomena associated with hip surgery, bearing surfaces (including
      metal-on-metal articulations), outcomes of hip replacement surgery and revision
      hip replacement. We present a concise report of the current opinions on hip
      surgery from this meeting with appropriate references to the current literature.

PMID- 22371534
TI  - The influence of acetabular inclination angle on the penetration of polyethylene
      and migration of the acetabular component: a prospective, radiostereometric study
      on cemented acetabular components.
AB  - In this prospective study we studied the effect of the inclination angle of the
      acetabular component on polyethylene wear and component migration in cemented
      acetabular sockets using radiostereometric analysis. A total of 120 patients
      received either a cemented Reflection All-Poly ultra-high-molecular-weight
      polyethylene or a cemented Reflection All-Poly highly cross-linked polyethylene
      acetabular component, combined with either cobalt-chrome or Oxinium femoral
      heads. Femoral head penetration and migration of the acetabular component were
      assessed with repeated radiostereometric analysis for two years. The inclination
      angle was measured on a standard post-operative anteroposterior pelvic
      radiograph. Linear regression analysis was used to determine the relationship
      between the inclination angle and femoral head penetration and migration of the
      acetabular component. We found no relationship between the inclination angle and
      penetration of the femoral head at two years' follow-up (p = 0.9). Similarly, our
      data failed to reveal any statistically significant correlation between
      inclination angle and migration of these cemented acetabular components (p = 0.07
      to p = 0.9).

PMID- 22371535
TI  - Long-term results of conventional varus half-wedge proximal femoral osteotomy for
      the treatment of osteonecrosis of the femoral head.
AB  - We have previously described the mid- to long-term results of conventional simple
      varus intertrochanteric osteotomy for osteonecrosis of the femoral head, showing
      that 19 of the 26 hips had good or excellent results. We extended the follow-up
      to a mean of 18.1 years (10.5 to 26) including a total of 34 hips in 28 patients,
      with a mean age at surgery of 33 years (19 to 53). There were 18 men and ten
      women and 25 hips (74%) had a satisfactory result with a Harris hip score >= 80.
      In all, six hips needed total hip replacement (THR) or hemiarthroplasty. The
      collapse of the femoral head or narrowing of the joint space was found to have
      progressed in nine hips (26%). Leg shortening after osteotomy was a mean of 19 mm
      (8 to 36). With conversion to THR or hemiarthroplasty as the endpoint, the ten
      year survival rate was 88.2% (95% confidence interval (CI) 82.7 to 93.7) and the
      20-year survival rate was 79.7% (95% CI 72.1 to 87.3); four hips were converted
      at ten years and other two hips were converted at 20 years. Shortening of the leg
      after osteotomy remains a concern; however, the conventional varus half-wedge
      osteotomy provides favourable long-term results in hips with less than two-thirds
      of the medial part of the femoral head affected by necrotic bone and with normal
      bone superolaterally.

PMID- 22371536
TI  - Birmingham hip resurfacing at a mean of ten years: results from an independent
      centre.
AB  - We report the findings of an independent review of 230 consecutive Birmingham hip
      resurfacings (BHRs) in 213 patients (230 hips) at a mean follow-up of 10.4 years
      (9.6 to 11.7). A total of 11 hips underwent revision; six patients (six hips)
      died from unrelated causes; and 13 patients (16 hips) were lost to follow-up. The
      survival rate for the whole cohort was 94.5% (95% confidence interval (CI) 90.1
      to 96.9). The survival rate in women was 89.1% (95% CI 79.2 to 94.4) and in men
      was 97.5% (95% CI 92.4 to 99.2). Women were 1.4 times more likely to suffer
      failure than men. For each millimetre increase in component size there was a 19%
      lower chance of a failure. The mean Oxford hip score was 45.0 (median 47.0, 28 to
      48); mean University of California, Los Angeles activity score was 7.4 (median
      8.0, 3 to 9); mean patient satisfaction score was 1.4 (median 1.0, 0 to 9). A
      total of eight hips had lysis in the femoral neck and two hips had acetabular
      lysis. One hip had progressive radiological changes around the peg of the femoral
      component. There was no evidence of progressive neck narrowing between five and
      ten years. Our results confirm that BHR provides good functional outcome and
      durability for men, at a mean follow-up of ten years. We are now reluctant to
      undertake hip resurfacing in women with this implant.

PMID- 22371537
TI  - Preservation of the original femoral cement mantle during the management of
      infected cemented total hip replacement by two-stage revision.
AB  - The removal of all prosthetic material and a two-stage revision procedure is the
      established standard management of an infected total hip replacement (THR).
      However, the removal of well-fixed femoral cement is time-consuming and can
      result in significant loss of bone stock and femoral shaft perforation or
      fracture. We report our results of two-stage revision THR for treating infection,
      with retention of the original well-fixed femoral cement mantle in 15 patients,
      who were treated between 1989 and 2002. Following partial excision arthroplasty,
      patients received local and systemic antibiotics and underwent reconstruction and
      re-implantation at a second-stage procedure, when the infection had resolved. The
      mean follow-up of these 15 patients was 82 months (60 to 192). Two patients had
      positive microbiology at the second stage and were treated with six weeks of
      appropriate antibiotics; one of these developed recurrent infection requiring
      further revision. Successful eradication of infection was achieved in the
      remaining 14 patients. We conclude that when two-stage revision is used for the
      treatment of peri-prosthetic infection involving a THR, a well-fixed femoral
      cement mantle can be safely left in situ, without compromising the treatment of
      infection. Advantages of this technique include a shorter operating time, reduced
      loss of bone stock and a technically more straightforward second-stage procedure.

PMID- 22371538
TI  - The long-term function of the knee in patients with fibular hemimelia and
      anterior cruciate ligament deficiency.
AB  - Most patients (95%) with fibular hemimelia have an absent anterior cruciate
      ligament (ACL). The purpose of this study was to assess the long-term outcome of
      such patients with respect to pain and knee function. We performed a
      retrospective review of patients with fibular hemimelia and associated ACL
      deficiency previously treated at our institution. Of a possible 66 patients, 23
      were sent the Musculoskeletal Outcomes Data Evaluation and Management System
      (MODEMS) questionnaire and Lysholm knee score to complete. In all, 11 patients
      completed the MODEMS and nine completed the Lysholm score questionnaire. Their
      mean age was 37 years (27 to 57) at review. Five patients had undergone an
      ipsilateral Symes amputation. There was no significant difference in any
      subsections of the Short-Form 36 scores of our patients compared with age-matched
      controls. The mean Lysholm knee score was 90.2 (82 to 100). A slight limp was
      reported in six patients. No patients had episodes of locking of the knee or
      required a supportive device for walking. Four had occasional instability with
      sporting activities.  These results suggest that patients with fibular hemimelia
      and ACL deficiency can live active lives with a similar health status to age
      matched controls.

PMID- 22371539
TI  - The early radiological results of the uncemented Oxford medial compartment knee
      replacement.
AB  - We carried out a prospective investigation into the radiological outcomes of
      uncemented Oxford medial compartment unicondylar replacement in 220 consecutive
      patients (231 knees) performed in a single centre with a minimum two-year follow
      up. The functional outcomes using the mean Oxford knee score and the mean high
      activity arthroplasty score were significantly improved over the pre-operative
      scores (p < 0.001). There were 196 patients with a two-year radiological
      examination performed under fluoroscopic guidance, aiming to provide images
      acceptable for analysis of the bone-implant interface. Of the six tibial zones
      examined on each knee on the anteroposterior radiograph, only three had a partial
      radiolucent line. All were in the medial aspect of the tibial base plate (zone 1)
      and all measured < 1 mm. All of these patients were asymptomatic. There were no
      radiolucent lines seen around the femoral component or on the lateral view. There
      was one revision for loosening at one year due to initial inadequate seating of
      the tibial component. These results confirm that the early uncemented Oxford
      medial unicompartmental compartmental knee replacements were reliable and the
      incidence of radiolucent lines was significantly decreased compared with the
      reported results of cemented versions of this implant. These independent results
      confirm those of the designing centre.

PMID- 22371540
TI  - Custom rotating-hinge primary total knee arthroplasty in patients with skeletal
      dysplasia.
AB  - Patients with skeletal dysplasia are prone to developing advanced osteoarthritis
      of the knee requiring total knee replacement (TKR) at a younger age than the
      general population. TKR in this unique group of patients is a technically
      demanding procedure owing to the deformity, flexion contracture, generalised
      hypotonia and ligamentous laxity. We retrospectively reviewed the outcome of 11
      TKRs performed in eight patients with skeletal dysplasia at our institution using
      the Stanmore Modular Individualised Lower Extremity System (SMILES) custom-made
      rotating-hinge TKR. There were three men and five women with mean age of 57 years
      (41 to 79). Patients were followed clinically and radiologically for a mean of
      seven years (3 to 11.5). The mean Knee Society clinical and function scores
      improved from 24 (14 to 36) and 20 (5 to 40) pre-operatively, respectively, to 68
      (28 to 80) and 50 (22 to 74), respectively, at final follow-up. Four
      complications were recorded, including a patellar fracture following a fall, a
      tibial peri-prosthetic fracture, persistent anterior knee pain, and aseptic
      loosening of a femoral component requiring revision. Our results demonstrate that
      custom primary rotating-hinge TKR in patients with skeletal dysplasia is
      effective at relieving pain, with a satisfactory range of movement and improved
      function. It compensates for bony deformity and ligament deficiency and reduces
      the likelihood of corrective osteotomy. Patellofemoral joint complications are
      frequent and functional outcome is worse than with primary TKR in the general
      population.

PMID- 22371541
TI  - Doppler spectrum analysis: a potentially useful diagnostic tool for planning the
      treatment of patients with Charcot arthropathy of the foot?
AB  - It is difficult to determine the safe timing of weight-bearing or reconstructive
      surgery in patients with Charcot arthropathy of the foot and ankle. In this study
      the Doppler spectrum of the first dorsal metatarsal artery was used to monitor
      the activity of the disease activity and served as a guideline for management. A
      total of 15 patients (seven men and eight women) with acute diabetic Charcot
      arthropathy of the foot and ankle were immobilised in a non-weight-bearing cast.
      They were followed at two-week intervals and bilateral Doppler spectra of the
      first dorsal metatarsal arteries were obtained using a 10 MHz linear ultrasound
      probe. The patients were allowed to start weight-bearing or undergo surgery after
      the Doppler spectrum had returned to normal pattern. The Doppler spectra in the
      unaffected limbs were triphasic in pattern, whereas those in limbs with active
      Charcot arthropathy showed monophasic forward flow. They returned to normal after
      a mean of 13.6 weeks (6 to 20) of immobilisation. Three patients underwent pan
      talar arthrodesis to correct gross instability and deformity. Doppler spectrum
      analysis of the foot may reflect the activity of the disease in patients with
      Charcot arthropathy, and may be used as a guide to begin weight-bearing or
      undergo reconstructive surgery.

PMID- 22371542
TI  - Outcomes of open arthrolysis of the elbow without post-operative passive
      stretching.
AB  - The use of passive stretching of the elbow after arthrolysis is controversial. We
      report the results of open arthrolysis in 81 patients. Prospectively collected
      outcome data with a minimum follow-up of one year were analysed. All patients had
      sustained an intra-articular fracture initially and all procedures were performed
      by the same surgeon under continuous brachial plexus block anaesthesia and with
      continuous passive movement (CPM) used post-operatively for two to three days.
      CPM was used to maintain the movement achieved during surgery and passive
      stretching was not used at any time. A senior physiotherapist assessed all the
      patients at regular intervals. The mean range of movement (ROM) improved from 69
      degrees  to 109 degrees  and the function and pain of the upper limb improved
      from 32 to 16 and from 20 to 10, as assessed by the Disabilities of the Arm
      Shoulder and Hand score and a visual analogue scale, respectively. The greatest
      improvement was obtained in the stiffest elbows: nine patients with a pre
      operative ROM < 30 degrees  achieved a mean post-operative ROM of 92 degrees  (55
      degrees  to 125 degrees ). This study demonstrates that in patients with a stiff
      elbow after injury, good results may be obtained after open elbow arthrolysis
      without using passive stretching during rehabilitation.

PMID- 22371543
TI  - The role of arthroscopic synovectomy in patients with undifferentiated chronic
      monoarthritis of the wrist.
AB  - We investigated the clinical response to arthroscopic synovectomy in patients
      with undifferentiated chronic monoarthritis (UCMA) of the wrist. Arthroscopic
      synovectomy was performed on 20 wrists in 20 patients with UCMA of the wrist who
      had not responded to non-steroidal anti-inflammatory drugs. The mean duration of
      symptoms at the time of surgery was 4.3 months (3 to 7) and the mean follow-up
      was 51.8 months (24 to 94). Inflamed synovium was completely removed from the
      radiocarpal, midcarpal and distal radioulnar joints using more portals than
      normal. After surgery, nine patients had early remission of synovitis and 11 with
      uncontrolled synovitis received antirheumatic medication. Overall, there was
      significant improvement in terms of pain relief, range of movement and Mayo
      score. Radiological deterioration was seen in five patients who were diagnosed as
      having rheumatoid arthritis during the follow-up period. Lymphoid follicles and
      severe lymphocyte infiltration were seen more often in synovial biopsies from
      patients with uncontrolled synovitis. These results suggest that arthroscopic
      synovectomy provides pain relief and functional improvement, and allows rapid
      resolution of synovitis in about half of patients with UCMA of the wrist.

PMID- 22371544
TI  - National in-hospital morbidity and mortality trends after lumbar fusion surgery
      between 1998 and 2008.
AB  - Increasing numbers of posterior lumbar fusions are being performed. The purpose
      of this study was to identify trends in demographics, mortality and major
      complications in patients undergoing primary posterior lumbar fusion. We accessed
      data collected for the Nationwide Inpatient Sample for each year between 1998 and
      2008 and analysed trends in the number of lumbar fusions, mean patient age,
      comorbidity burden, length of hospital stay, discharge status, major peri
      operative complications and mortality. An estimated 1 288 496 primary posterior
      lumbar fusion operations were performed between 1998 and 2008 in the United
      States. The total number of procedures, mean patient age and comorbidity burden
      increased over time. Hospital length of stay decreased, although the in-hospital
      mortality (adjusted and unadjusted for changes in length of hospital stay)
      remained stable. However, a significant increase was observed in peri-operative
      septic, pulmonary and cardiac complications. Although in-hospital mortality rates
      did not change over time in the setting of increases in mean patient age and
      comorbidity burden, some major peri-operative complications increased. These
      trends highlight the need for appropriate peri-operative services to optimise
      outcomes in an increasingly morbid and older population of patients undergoing
      lumbar fusion.

PMID- 22371545
TI  - Diastematomyelia: a retrospective review of 138 patients.
AB  - Diastematomyelia is a rare congenital abnormality of the spinal cord. This paper
      summarises more than 30 years' experience of treating this condition. Data were
      collected retrospectively on 138 patients with diastematomyelia (34 males, 104
      females) who were treated at our hospital from May 1978 to April 2010. A total of
      106 patients had double dural tubes (type 1 diastematomyelia), and 32 patients
      had single dural tubes (type 2 diastematomyelia). Radiographs, CT myelography,
      and MRI showed characteristic kyphoscoliosis, widening of the interpedicle
      distance, and bony, cartilaginous, and fibrous septum. The incidences of symptoms
      including characteristic changes of the dorsal skin, neurological disorders, and
      congenital spinal or foot deformity were significantly higher in type 1 than in
      type 2. Surgery is more effective for patients with type 1 diastematomyelia;
      patients without surgery showed no improvement.

PMID- 22371546
TI  - Posterior lumbar interbody fusion using spinous process and laminae.
AB  - Posterior lumbar interbody fusion (PLIF) is indicated for many patients with pain
      and/or instability of the lumbar spine. We performed 36 PLIF procedures using the
      patient's lumbar spinous process and laminae, which were inserted as a bone graft
      between two vertebral bodies without using a cage. The mean lumbar lordosis and
      mean disc height to vertebral body ratio were restored and preserved after
      surgery. There were no serious complications. These results suggest that this
      procedure is safe and effective.

PMID- 22371547
TI  - The natural history of asymptomatic lumbar canal stenosis in patients undergoing
      surgery for cervical myelopathy.
AB  - We retrospectively examined the prevalence and natural history of asymptomatic
      lumbar canal stenosis in patients treated surgically for cervical compressive
      myelopathy in order to assess the influence of latent lumbar canal stenosis on
      the recovery after surgery. Of 214 patients who had undergone cervical
      laminoplasty for cervical myelopathy, we identified 69 (32%) with
      myelographically documented lumbar canal stenosis. Of these, 28 (13%) patients
      with symptomatic lumbar canal stenosis underwent simultaneous cervical and lumbar
      decompression. Of the remaining 41 (19%) patients with asymptomatic lumbar canal
      stenosis who underwent only cervical surgery, 39 were followed up for >= 1 year
      (mean 4.9 years (1 to 12)) and were included in the analysis (study group).
      Patients without myelographic evidence of lumbar canal stenosis, who had been
      followed up for >= 1 year after the cervical surgery, served as controls (135
      patients; mean follow-up period 6.5 years (1 to 17)). Among the 39 patients with
      asymptomatic lumbar canal stenosis, seven had lumbar-related leg symptoms after
      the cervical surgery. Kaplan-Meier analysis showed that 89.6% (95% confidence
      interval (CI) 75.3 to 96.0) and 76.7% (95% CI 53.7 to 90.3) of the patients with
      asymptomatic lumbar canal stenosis were free from leg symptoms for three and five
      years, respectively. There were no significant differences between the study and
      control groups in the recovery rate measured by the Japanese Orthopaedic
      Association score or improvement in the Nurick score at one year after surgery or
      at the final follow-up. These results suggest that latent lumbar canal stenosis
      does not influence recovery following surgery for cervical myelopathy; moreover,
      prophylactic lumbar decompression does not appear to be warranted as a routine
      procedure for coexistent asymptomatic lumbar canal stenosis in patients with
      cervical myelopathy, when planning cervical surgery.

PMID- 22371548
TI  - Atypical femoral fractures and bisphosphonate treatment: experience in two large
      United Kingdom teaching hospitals.
AB  - We performed a retrospective review of all patients admitted to two large
      University Hospitals in the United Kingdom over a 24-month period from January
      2008 to January 2010 to identify the incidence of atypical subtrochanteric and
      femoral shaft fractures and their relationship to bisphosphonate treatment. Of
      the 3515 patients with a fracture of the proximal femur, 156 fractures were in
      the subtrochanteric region. There were 251 femoral shaft fractures. The atypical
      fracture pattern was seen in 27 patients (7%) with 29 femoral shaft or
      subtrochanteric fractures. A total of 22 patients with 24 atypical fractures were
      receiving bisphosphonate treatment at the time of fracture. Prodromal pain was
      present in nine patients (11 fractures); 11 (50%) of the patients on
      bisphosphonates suffered 12 spontaneous fractures, and healing of these fractures
      was delayed in a number of patients. This large dual-centre review has
      established the incidence of atypical femoral fractures at 7% of the study
      population, 81% of whom had been on bisphosphonate treatment for a mean of 4.6
      years (0.04 to 12.1). This study does not advocate any change in the use of
      bisphosphonates to prevent fragility fractures but attempts to raise awareness of
      this possible problem so symptomatic patients will be appropriately investigated.
      However, more work is required to identify the true extent of this new and
      possibly increasing problem.

PMID- 22371549
TI  - Sliding hip screw versus the Targon PF nail in the treatment of trochanteric
      fractures of the hip: a randomised trial of 600 fractures.
AB  - In a randomised trial involving 598 patients with 600 trochanteric fractures of
      the hip, the fractures were treated with either a sliding hip screw (n = 300) or
      a Targon PF intramedullary nail (n = 300). The mean age of the patients was 82
      years (26 to 104). All surviving patients were reviewed at one year with
      functional outcome assessed by a research nurse blinded to the treatment used.
      The intramedullary nail was found to have a slightly increased mean operative
      time (46 minutes (sd 12.3) versus 49 minutes (sd 12.7), p < 0.001) and an
      increased mean radiological screening time (0.3 minutes (sd 0.2) versus 0.5
      minutes (sd 0.3), p < 0.001). Operative difficulties were more common with the
      intramedullary nail. There was no statistically significant difference between
      implants for wound healing complications (p = 1), or need for post-operative
      blood transfusion (p = 1), and medical complications were similarly distributed
      in both groups. There was a tendency to fewer revisions of fixation or conversion
      to an arthroplasty in the nail group, although the difference was not
      statistically significant (nine versus three cases, p = 0.14). The extent of
      shortening, loss of hip flexion, mortality and degree of residual pain were
      similar in both groups. The recovery of mobility was superior for those treated
      with the intramedullary nails (p = 0.01 at one year from injury). In summary,
      both implants produced comparable results but there was a tendency to better
      return of mobility for those treated with the intramedullary nail.

PMID- 22371550
TI  - Telemetric assessment of bone healing with an instrumented internal fixator: a
      preliminary study.
AB  - In an interdisciplinary project involving electronic engineers and clinicians, a
      telemetric system was developed to measure the bending load in a titanium
      internal femoral fixator. As this was a new device, the main question posed was:
      what clinically relevant information could be drawn from its application? As a
      first clinical investigation, 27 patients (24 men, three women) with a mean age
      of 38.4 years (19 to 66) with femoral nonunions were treated using the system.
      The mean duration of the nonunion was 15.4 months (5 to 69). The elasticity of
      the plate-callus system was measured telemetrically until union. Conventional
      radiographs and a CT scan at 12 weeks were performed routinely, and healing was
      staged according to the CT scans. All nonunions healed at a mean of 21.5 weeks
      (13 to 37). Well before any radiological signs of healing could be detected, a
      substantial decrease in elasticity was recorded. The relative elasticity
      decreased to 50% at a mean of 7.8 weeks (3.5 to 13) and to 10% at a mean of 19.3
      weeks (4.5 to 37). At 12 weeks the mean relative elasticity was 28.1% (0% to
      56%). The relative elasticity was significantly different between the different
      healing stages as determined by the CT scans. Incorporating load measuring
      electronics into implants is a promising option for the assessment of bone
      healing. Future application might lead to a reduction in the need for exposure to
      ionising radiation to monitor fracture healing.

PMID- 22371551
TI  - The Pararectus approach for anterior intrapelvic management of acetabular
      fractures: an anatomical study and clinical evaluation.
AB  - A new anterior intrapelvic approach for the surgical management of displaced
      acetabular fractures involving predominantly the anterior column and the
      quadrilateral plate is described. In order to establish five 'windows' for
      instrumentation, the extraperitoneal space is entered along the lateral border of
      the rectus abdominis muscle. This is the so-called 'Pararectus' approach. The
      feasibility of safe dissection and optimal instrumentation of the pelvis was
      assessed in five cadavers (ten hemipelves) before implementation in a series of
      20 patients with a mean age of 59 years (17 to 90), of whom 17 were male. The
      clinical evaluation was undertaken between December 2009 and December 2010. The
      quality of reduction was assessed with post-operative CT scans and the occurrence
      of intra-operative complications was noted. In cadavers, sufficient
      extraperitoneal access and safe instrumentation of the pelvis were accomplished.
      In the patients, there was a statistically significant improvement in the
      reduction of the fracture (pre- versus post-operative: mean step-off 3.3 mm (sd
      2.6) vs 0.1 mm (sd 0.3), p < 0.001; and mean gap 11.5 mm (sd 6.5) vs 0.8 mm (sd
      1.3), p < 0.001). Lesions to the peritoneum were noted in two patients and minor
      vascular damage was noted in a further two patients. Multi-directional screw
      placement and various plate configurations were feasible in cadavers without
      significant retraction of soft tissues. In the treatment of acetabular fractures
      predominantly involving the anterior column and the quadrilateral plate, the
      Pararectus approach allowed anatomical restoration with minimal morbidity related
      to the surgical access.

PMID- 22371552
TI  - Interpretation of patient-reported outcomes for hip and knee replacement surgery:
      identification of thresholds associated with satisfaction with surgery.
AB  - We obtained information from the Elective Orthopaedic Centre on 1523 patients
      with baseline and six-month Oxford hip scores (OHS) after undergoing primary hip
      replacement (THR) and 1784 patients with Oxford knee scores (OKS) for primary
      knee replacement (TKR) who completed a six-month satisfaction questionnaire.
      Receiver operating characteristic curves identified an absolute change in OHS of
      14 points or more as the point that discriminates best between patients'
      satisfaction levels and an 11-point change for the OKS. Satisfaction is highest
      (97.6%) in patients with an absolute change in OHS of 14 points or more, compared
      with lower levels of satisfaction (81.8%) below this threshold. Similarly, an 11
      point absolute change in OKS was associated with 95.4% satisfaction compared with
      76.5% below this threshold. For the six-month OHS a score of 35 points or more
      distinguished patients with the highest satisfaction level, and for the six-month
      OKS 30 points or more identified the highest level of satisfaction. The
      thresholds varied according to patients' pre-operative score, where those with
      severe pre-operative pain/function required a lower six-month score to achieve
      the highest levels of satisfaction. Our data suggest that the choice of a six
      month follow-up to assess patient-reported outcomes of THR/TKR is acceptable. The
      thresholds help to differentiate between patients with different levels of
      satisfaction, but external validation will be required prior to general
      implementation in clinical practice.

PMID- 22371553
TI  - A preliminary investigation of Beta-hCG expression in patients with osteosarcoma.
AB  - There are eight reported cases in the literature of osteosarcomas secreting beta
      hCG. Our primary aim was to investigate the rate of beta-hCG expression in
      osteosarcoma and attempt to understand the characteristics of osteosarcomas that
      secrete beta-hCG. We reviewed 37 histopathology slides (14 biopsies and 23
      surgical specimens) from 32 patients with osteosarcoma. The slides were
      retrospectively stained for beta-hCG expression. Patient and tumour
      characteristics, including age, gender, tumour location, subtype, proportion of
      necrosis, presence of metastases and recurrence were recorded. A total of five of
      the 32 tumours were found to be positive for beta-hCG expression (one strongly
      and four weakly). This incidence of this expression was found in tumours with
      poor histological response to neoadjuvant chemotherapy. The use of beta-hCG
      expression as a diagnostic, prognostic or follow-up marker is questionable and
      needs further investigation with a larger sample size.

PMID- 22371554
TI  - The medium-term results of the Stanmore non-invasive extendible endoprosthesis in
      the treatment of paediatric bone tumours.
AB  - In skeletally immature patients, resection of bone tumours and reconstruction of
      the lower limb often results in leg-length discrepancy. The Stanmore non-invasive
      extendible endoprosthesis, which uses electromagnetic induction, allows post
      operative lengthening without anaesthesia. Between 2002 and 2009, 55 children
      with a mean age of 11.4 years (5 to 16) underwent reconstruction with this
      prosthesis; ten patients (18.2%) died of disseminated disease and one child
      underwent amputation due to infection. We reviewed 44 patients after a mean
      follow-up of 41.2 months (22 to 104). The mean Musculoskeletal Tumor Society
      score was 24.7 (8 to 30) and the Toronto Extremity Salvage score was 92.3% (55.2%
      to 99.0%). There was no local recurrence of tumour. Complications developed in 16
      patients (29.1%) and ten (18.2%) underwent revision. The mean length gained per
      patient was 38.6 mm (3.5 to 161.5), requiring a mean of 11.3 extensions (1 to
      40), and ten component exchanges were performed in nine patients (16.4%) after
      attaining the maximum lengthening capacity of the implant. There were 11 patients
      (20%) who were skeletally mature at follow-up, ten of whom had equal leg lengths
      and nine had a full range of movement of the hip and knee. This is the largest
      reported series using non-invasive extendible endoprostheses after excision of
      primary bone tumours in skeletally immature patients. The technique produces a
      good functional outcome, with prevention of limb-length discrepancy at skeletal
      maturity.

PMID- 22371556
TI  - aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight
      junction formation.
AB  - The PAR-3-atypical protein kinase C (aPKC)-PAR-6 complex has been implicated in
      the development of apicobasal polarity and the formation of tight junctions (TJs)
      in vertebrate epithelial cells. It is recruited by junctional adhesion molecule A
      (JAM-A) to primordial junctions where aPKC is activated by Rho family small
      guanosine triphosphatases. In this paper, we show that aPKC can interact directly
      with JAM-A in a PAR-3-independent manner. Upon recruitment to primordial
      junctions, aPKC phosphorylates JAM-A at S285 to promote the maturation of
      immature cell-cell contacts. In fully polarized cells, S285-phosphorylated JAM-A
      is localized exclusively at the TJs, and S285 phosphorylation of JAM-A is
      required for the development of a functional epithelial barrier. Protein
      phosphatase 2A dephosphorylates JAM-A at S285, suggesting that it antagonizes the
      activity of aPKC. Expression of nonphosphorylatable JAM-A/S285A interferes with
      single lumen specification during cyst development in three-dimensional culture.
      Our data suggest that aPKC phosphorylates JAM-A at S285 to regulate cell-cell
      contact maturation, TJ formation, and single lumen specification.

PMID- 22371557
TI  - Aurora B controls kinetochore-microtubule attachments by inhibiting Ska complex
      KMN network interaction.
AB  - The KMN network (named according to the acronym for KNL1, Mis12, and Ndc80) and
      the more recently identified Ska complex (Ska1-3) have been shown to mediate
      kinetochore (KT)-microtubule (MT) attachments. How these two complexes cooperate
      to achieve stable end-on attachments remains unknown. In this paper, we show that
      Aurora B negatively regulates the localization of the Ska complex to KTs and that
      recruitment of the Ska complex to KTs depends on the KMN network. We identified
      interactions between members of the KMN and Ska complexes and demonstrated that
      these interactions are regulated by Aurora B. Aurora B directly phosphorylated
      Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3
      impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers),
      disrupting mitotic progression. We propose that Aurora B phosphorylation
      antagonizes the interaction between the Ska complex and the KMN network, thereby
      controlling Ska recruitment to KTs and stabilization of KT-MT attachments.

PMID- 22371558
TI  - The rate of change in Ca(2+) concentration controls sperm chemotaxis.
AB  - During chemotaxis and phototaxis, sperm, algae, marine zooplankton, and other
      microswimmers move on helical paths or drifting circles by rhythmically bending
      cell protrusions called motile cilia or flagella. Sperm of marine invertebrates
      navigate in a chemoattractant gradient by adjusting the flagellar waveform and,
      thereby, the swimming path. The waveform is periodically modulated by Ca(2+)
      oscillations. How Ca(2+) signals elicit steering responses and shape the path is
      unknown. We unveil the signal transfer between the changes in intracellular
      Ca(2+) concentration ([Ca(2+)](i)) and path curvature (kappa). We show that kappa
      is modulated by the time derivative d[Ca(2+)](i)/dt rather than the absolute
      [Ca(2+)](i). Furthermore, simulation of swimming paths using various Ca(2+)
      waveforms reproduces the wealth of swimming paths observed for sperm of marine
      invertebrates. We propose a cellular mechanism for a chemical differentiator that
      computes a time derivative. The cytoskeleton of cilia, the axoneme, is highly
      conserved. Thus, motile ciliated cells in general might use a similar cellular
      computation to translate changes of [Ca(2+)](i) into motion.

PMID- 22371559
TI  - Indirect inhibition of 26S proteasome activity in a cellular model of
      Huntington's disease.
AB  - Pathognomonic accumulation of ubiquitin (Ub) conjugates in human
      neurodegenerative diseases, such as Huntington's disease, suggests that highly
      aggregated proteins interfere with 26S proteasome activity. In this paper, we
      examine possible mechanisms by which an N-terminal fragment of mutant huntingtin
      (htt; N-htt) inhibits 26S function. We show that ubiquitinated N-htt-whether
      aggregated or not-did not choke or clog the proteasome. Both Ub-dependent and Ub
      independent proteasome reporters accumulated when the concentration of mutant N
      htt exceeded a solubility threshold, indicating that stabilization of 26S
      substrates is not linked to impaired Ub conjugation. Above this solubility
      threshold, mutant N-htt was rapidly recruited to cytoplasmic inclusions that were
      initially devoid of Ub. Although synthetically polyubiquitinated N-htt competed
      with other Ub conjugates for access to the proteasome, the vast majority of
      mutant N-htt in cells was not Ub conjugated. Our data confirm that proteasomes
      are not directly impaired by aggregated N-terminal fragments of htt; instead, our
      data suggest that Ub accumulation is linked to impaired function of the cellular
      proteostasis network.

PMID- 22371561
TI  - Space environment of an asteroid preserved on micrograins returned by the
      Hayabusa spacecraft.
AB  - Records of micrometeorite collisions at down to submicron scales were discovered
      on dust grains recovered from near-Earth asteroid 25143 (Itokawa). Because the
      grains were sampled from very near the surface of the asteroid, by the Hayabusa
      spacecraft, their surfaces reflect the low-gravity space environment influencing
      the physical nature of the asteroid exterior. The space environment was examined
      by description of grain surfaces and asteroidal scenes were reconstructed.
      Chemical and O isotope compositions of five lithic grains, with diameters near 50
      MUm, indicate that the uppermost layer of the rubble-pile-textured Itokawa is
      largely composed of equilibrated LL-ordinary-chondrite-like material with
      superimposed effects of collisions. The surfaces of the grains are dominated by
      fractures, and the fracture planes contain not only sub-MUm-sized craters but
      also a large number of sub-MUm- to several-MUm-sized adhered particles, some of
      the latter composed of glass. The size distribution and chemical compositions of
      the adhered particles, together with the occurrences of the sub-MUm-sized
      craters, suggest formation by hypervelocity collisions of micrometeorites at down
      to nm scales, a process expected in the physically hostile environment at an
      asteroid's surface. We describe impact-related phenomena, ranging in scale from
      10(-9) to 10(4) meters, demonstrating the central role played by impact processes
      in the long-term evolution of planetary bodies. Impact appears to be an important
      process shaping the exteriors of not only large planetary bodies, such as the
      moon, but also low-gravity bodies such as asteroids.

PMID- 22371560
TI  - Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling
      occurs primarily at the plasma membrane.
AB  - The role of endocytosis in the control of EGF receptor (EGFR) activation and cell
      signaling was explored by using mouse fibroblasts in which dynamin was
      conditionally depleted. Dynamin is a GTPase shown to play an important role in
      the control clathrin mediated endocytosis of EGFR and other cell surface
      receptors. In this report, we demonstrate that EGF binding activity and the
      display of high and low affinity EGFRs on the cell surface are not affected by
      dynamin depletion. By contrast, dynamin depletion leads to a strong inhibition of
      EGFR endocytosis, robust enhancement of EGFR autophosphorylation and
      ubiquitination, and slower kinetics of EGFR degradation. Surprisingly, MAPK
      stimulation induced by either low or high EGF concentrations is not affected by
      dynamin depletion. While a similar initial Akt response is detected in control or
      dynamin depleted fibroblasts, a somewhat more sustained Akt stimulation is
      detected in the dynamin depleted cells. These experiments demonstrate that
      dynamin-mediated endocytosis leads to attenuation of EGFR activation and
      degradation and that stimulation of the MAPK response and Akt activation are
      primarily mediated by activated EGFR located in the plasma membrane.

PMID- 22371562
TI  - Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain
      elongation.
AB  - Multimodular polyketide synthases (PKSs) have an assembly line architecture in
      which a set of protein domains, known as a module, participates in one round of
      polyketide chain elongation and associated chemical modifications, after which
      the growing chain is translocated to the next PKS module. The ability to
      rationally reprogram these assembly lines to enable efficient synthesis of new
      polyketide antibiotics has been a long-standing goal in natural products
      biosynthesis. We have identified a ratchet mechanism that can explain the
      observed unidirectional translocation of the growing polyketide chain along the 6
      deoxyerythronolide B synthase. As a test of this model, module 3 of the 6
      deoxyerythronolide B synthase has been reengineered to catalyze two successive
      rounds of chain elongation. Our results suggest that high selectivity has been
      evolutionarily programmed at three types of protein-protein interfaces that are
      present repetitively along naturally occurring PKS assembly lines.

PMID- 22371563
TI  - Impact of declining Arctic sea ice on winter snowfall.
AB  - While the Arctic region has been warming strongly in recent decades, anomalously
      large snowfall in recent winters has affected large parts of North America,
      Europe, and east Asia. Here we demonstrate that the decrease in autumn Arctic sea
      ice area is linked to changes in the winter Northern Hemisphere atmospheric
      circulation that have some resemblance to the negative phase of the winter Arctic
      oscillation. However, the atmospheric circulation change linked to the reduction
      of sea ice shows much broader meridional meanders in midlatitudes and clearly
      different interannual variability than the classical Arctic oscillation. This
      circulation change results in more frequent episodes of blocking patterns that
      lead to increased cold surges over large parts of northern continents. Moreover,
      the increase in atmospheric water vapor content in the Arctic region during late
      autumn and winter driven locally by the reduction of sea ice provides enhanced
      moisture sources, supporting increased heavy snowfall in Europe during early
      winter and the northeastern and midwestern United States during winter. We
      conclude that the recent decline of Arctic sea ice has played a critical role in
      recent cold and snowy winters.

PMID- 22371564
TI  - Distribution of fixed beneficial mutations and the rate of adaptation in asexual
      populations.
AB  - When large asexual populations adapt, competition between simultaneously
      segregating mutations slows the rate of adaptation and restricts the set of
      mutations that eventually fix. This phenomenon of interference arises from
      competition between mutations of different strengths as well as competition
      between mutations that arise on different fitness backgrounds. Previous work has
      explored each of these effects in isolation, but the way they combine to
      influence the dynamics of adaptation remains largely unknown. Here, we describe a
      theoretical model to treat both aspects of interference in large populations. We
      calculate the rate of adaptation and the distribution of fixed mutational effects
      accumulated by the population. We focus particular attention on the case when the
      effects of beneficial mutations are exponentially distributed, as well as on a
      more general class of exponential-like distributions. In both cases, we show that
      the rate of adaptation and the influence of genetic background on the fixation of
      new mutants is equivalent to an effective model with a single selection
      coefficient and rescaled mutation rate, and we explicitly calculate these
      effective parameters. We find that the effective selection coefficient exactly
      coincides with the most common fixed mutational effect. This equivalence leads to
      an intuitive picture of the relative importance of different types of
      interference effects, which can shift dramatically as a function of the
      population size, mutation rate, and the underlying distribution of fitness
      effects.

PMID- 22371565
TI  - Fracture of crystalline silicon nanopillars during electrochemical lithium
      insertion.
AB  - From surface hardening of steels to doping of semiconductors, atom insertion in
      solids plays an important role in modifying chemical, physical, and electronic
      properties of materials for a variety of applications. High densities of atomic
      insertion in a solid can result in dramatic structural transformations and
      associated changes in mechanical behavior: This is particularly evident during
      electrochemical cycling of novel battery electrodes, such as alloying anodes,
      conversion oxides, and sulfur and oxygen cathodes. Silicon, which undergoes 400%
      volume expansion when alloying with lithium, is an extreme case and represents an
      excellent model system for study. Here, we show that fracture locations are
      highly anisotropic for lithiation of crystalline Si nanopillars and that fracture
      is strongly correlated with previously discovered anisotropic expansion. Contrary
      to earlier theoretical models based on diffusion-induced stresses where fracture
      is predicted to occur in the core of the pillars during lithiation, the observed
      cracks are present only in the amorphous lithiated shell. We also show that the
      critical fracture size is between about 240 and 360 nm and that it depends on the
      electrochemical reaction rate.

PMID- 22371567
TI  - Water reservoir maintained by cell growth fuels the spreading of a bacterial
      swarm.
AB  - Flagellated bacteria can swim across moist surfaces within a thin layer of fluid,
      a means for surface colonization known as swarming. This fluid spreads with the
      swarm, but how it does so is unclear. We used micron-sized air bubbles to study
      the motion of this fluid within swarms of Escherichia coli. The bubbles moved
      diffusively, with drift. Bubbles starting at the swarm edge drifted inward for
      the first 5 s and then moved outward. Bubbles starting 30 MUm from the swarm edge
      moved inward for the first 20 s, wandered around in place for the next 40 s, and
      then moved outward. Bubbles starting at 200 or 300 MUm from the edge moved
      outward or wandered around in place, respectively. So the general trend was
      inward near the outer edge of the swarm and outward farther inside, with flows
      converging on a region about 100 MUm from the swarm edge. We measured cellular
      metabolic activities with cells expressing a short-lived GFP and cell densities
      with cells labeled with a membrane fluorescent dye. The fluorescence plots were
      similar, with peaks about 80 MUm from the swarm edge and slopes that mimicked the
      particle drift rates. These plots suggest that net fluid flow is driven by cell
      growth. Fluid depth is largest in the multilayered region between approximately
      30 and 200 MUm from the swarm edge, where fluid agitation is more vigorous. This
      water reservoir travels with the swarm, fueling its spreading. Intercellular
      communication is not required; cells need only grow.

PMID- 22371568
TI  - The resilience and adaptive capacity of social-environmental systems in colonial
      Mexico.
AB  - Civilization collapse scenarios highlight what for some are worrying parallels
      between past case studies and societies under threat from apparently
      unprecedented global environmental and climate change today. Archive-based
      studies of socio-economic responses to climate variability in colonial Mexico
      suggest that the complex interactions between environment and society influence
      the degree to which regional livelihoods may be vulnerable or resilient to
      disruption and also illustrate that vulnerability to change can lead to improved
      understanding of risk and increased adaptive capacity. In this paper, I draw on
      examples to argue that experience of climate variability, extreme weather events,
      or weather-related events and crises can challenge societal resilience, but can
      also increase opportunities for learning and innovation, extending the repertoire
      of adaptive responses. The historical examples selected might help inform the
      degree to which societies can develop strategies to deal with environmental
      perturbations at different scales and highlight that social breakdown and
      collapse are not an inevitable result of transformation.

PMID- 22371566
TI  - Identification of neuronal substrates implicates Pak5 in synaptic vesicle
      trafficking.
AB  - Synaptic transmission is mediated by a complex set of molecular events that must
      be coordinated in time and space. While many proteins that function at the
      synapse have been identified, the signaling pathways regulating these molecules
      are poorly understood. Pak5 (p21-activated kinase 5) is a brain-specific isoform
      of the group II Pak kinases whose substrates and roles within the central nervous
      system are largely unknown. To gain insight into the physiological roles of Pak5,
      we engineered a Pak5 mutant to selectively radiolabel its substrates in murine
      brain extract. Using this approach, we identified two novel Pak5 substrates,
      Pacsin1 and Synaptojanin1, proteins that directly interact with one another to
      regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1
      were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5
      phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.
      These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic
      vesicle trafficking and may partially account for the cognitive and behavioral
      deficits observed in group II Pak-deficient mice.

PMID- 22371569
TI  - Induced mutations in circadian clock regulator Mat-a facilitated short-season
      adaptation and range extension in cultivated barley.
AB  - Time to flowering has an important impact on yield and has been a key trait in
      the domestication of crop plants and the spread of agriculture. In 1961, the
      cultivar Mari (mat-a.8) was the very first induced early barley (Hordeum vulgare
      L.) mutant to be released into commercial production. Mari extended the range of
      two-row spring barley cultivation as a result of its photoperiod insensitivity.
      Since its release, Mari or its derivatives have been used extensively across the
      world to facilitate short-season adaptation and further geographic range
      extension. By exploiting an extended historical collection of early-flowering
      mutants of barley, we identified Praematurum-a (Mat-a), the gene responsible for
      this key adaptive phenotype, as a homolog of the Arabidopsis thaliana circadian
      clock regulator Early Flowering 3 (Elf3). We characterized 87 induced mat-a
      mutant lines and identified >20 different mat-a alleles that had clear mutations
      leading to a defective putative ELF3 protein. Expression analysis of HvElf3 and
      Gigantea in mutant and wild-type plants demonstrated that mat-a mutations disturb
      the flowering pathway, leading to the early phenotype. Alleles of Mat-a therefore
      have important and demonstrated breeding value in barley but probably also in
      many other day-length-sensitive crop plants, where they may tune adaptation to
      different geographic regions and climatic conditions, a critical issue in times
      of global warming.

PMID- 22371571
TI  - Kax and kol: collapse and resilience in lowland Maya civilization.
AB  - Episodes of population loss and cultural change, including the famous Classic
      Collapse, punctuated the long course of Maya civilization. In many cases, these
      downturns in the fortunes of individual sites and entire regions included
      significant environmental components such as droughts or anthropogenic
      environmental degradation. Some afflicted areas remained depopulated for long
      periods, whereas others recovered more quickly. We examine the dynamics of growth
      and decline in several areas in the Maya Lowlands in terms of both environmental
      and cultural resilience and with a focus on downturns that occurred in the
      Terminal Preclassic (second century Common Era) and Terminal Classic (9th and
      10th centuries CE) periods. This examination of available data indicates that the
      elevated interior areas of the Yucatan Peninsula were more susceptible to system
      collapse and less suitable for resilient recovery than adjacent lower-lying
      areas.

PMID- 22371570
TI  - Orientation selectivity and noise correlation in awake monkey area V1 are
      modulated by the gamma cycle.
AB  - Gamma-band synchronization adjusts the timing of excitatory and inhibitory inputs
      to a neuron. Neurons in the visual cortex are selective for stimulus orientation
      because of dynamic interactions between excitatory and inhibitory inputs. We
      hypothesized that these interactions and hence also orientation selectivity vary
      during the gamma cycle. We determined for each spike its phase relative to the
      gamma cycle. As a function of gamma phase, we then determined spike rates and
      their orientation selectivity. Orientation selectivity was modulated by gamma
      phase. The firing rate of spiking activity that occurred close to a neuron's mean
      gamma phase of firing was most orientation selective. This stimulus-selective
      signal could best be conveyed to postsynaptic neurons if it were not corrupted by
      noise correlations. Noise correlations between firing rates were modulated by
      gamma phase such that they were not statistically detectable for the spiking
      activity occurring close to a neuron's mean gamma phase of firing. Thus, gamma
      band synchronization produces spiking activity that carries maximal stimulus
      selectivity and minimal noise correlation in its firing rate, and at the same
      time synchronizes this spiking activity for maximal impact on postsynaptic
      targets.

PMID- 22371572
TI  - Structural dissection of Ebola virus and its assembly determinants using cryo
      electron tomography.
AB  - Ebola virus is a highly pathogenic filovirus causing severe hemorrhagic fever
      with high mortality rates. It assembles heterogenous, filamentous, enveloped
      virus particles containing a negative-sense, single-stranded RNA genome packaged
      within a helical nucleocapsid (NC). We have used cryo-electron microscopy and
      tomography to visualize Ebola virus particles, as well as Ebola virus-like
      particles, in three dimensions in a near-native state. The NC within the virion
      forms a left-handed helix with an inner nucleoprotein layer decorated with
      protruding arms composed of VP24 and VP35. A comparison with the closely related
      Marburg virus shows that the N-terminal region of nucleoprotein defines the inner
      diameter of the Ebola virus NC, whereas the RNA genome defines its length.
      Binding of the nucleoprotein to RNA can assemble a loosely coiled NC-like
      structure; the loose coil can be condensed by binding of the viral matrix protein
      VP40 to the C terminus of the nucleoprotein, and rigidified by binding of VP24
      and VP35 to alternate copies of the nucleoprotein. Four proteins (NP, VP24, VP35,
      and VP40) are necessary and sufficient to mediate assembly of an NC with
      structure, symmetry, variability, and flexibility indistinguishable from that in
      Ebola virus particles released from infected cells. Together these data provide a
      structural and architectural description of Ebola virus and define the roles of
      viral proteins in its structure and assembly.

PMID- 22371573
TI  - Telomere maintenance and telomerase activity are differentially regulated in
      asexual and sexual worms.
AB  - In most sexually reproducing animals, replication and maintenance of telomeres
      occurs in the germ line and during early development in embryogenesis through the
      use of telomerase. Somatic cells generally do not maintain telomere sequences,
      and these cells become senescent in adults as telomeres shorten to a critical
      length. Some animals reproduce clonally and must therefore require adult somatic
      mechanisms for maintaining their chromosome ends. Here we study the telomere
      biology of planarian flatworms with apparently limitless regenerative capacity
      fueled by a population of highly proliferative adult stem cells. We show that
      somatic telomere maintenance is different in asexual and sexual animals. Asexual
      animals maintain telomere length somatically during reproduction by fission or
      when regeneration is induced by amputation, whereas sexual animals only achieve
      telomere elongation through sexual reproduction. We demonstrate that this
      difference is reflected in the expression and alternate splicing of the protein
      subunit of the telomerase enzyme. Asexual adult planarian stem cells appear to
      maintain telomere length over evolutionary timescales without passage through a
      germ-line stage. The adaptations we observe demonstrate indefinite somatic
      telomerase activity in proliferating stem cells during regeneration or
      reproduction by fission, and establish planarians as a pertinent model for
      studying telomere structure, function, and maintenance.

PMID- 22371574
TI  - Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic
      syndrome in mice.
AB  - Fructose intake from added sugars correlates with the epidemic rise in obesity,
      metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also
      causes features of metabolic syndrome in laboratory animals and humans. The first
      enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A
      and C. Here we show that fructose-induced metabolic syndrome is prevented in mice
      lacking both isoforms but is exacerbated in mice lacking fructokinase A.
      Fructokinase C is expressed primarily in liver, intestine, and kidney and has
      high affinity for fructose, resulting in rapid metabolism and marked ATP
      depletion. In contrast, fructokinase A is widely distributed, has low affinity
      for fructose, and has less dramatic effects on ATP levels. By reducing the amount
      of fructose for metabolism in the liver, fructokinase A protects against
      fructokinase C-mediated metabolic syndrome. These studies provide insights into
      the mechanisms by which fructose causes obesity and metabolic syndrome.

PMID- 22371575
TI  - Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents
      tumor metastasis.
AB  - Hyaluronic acid (HA) has been implicated in the proliferation and metastasis of
      tumor cells. However, most previous studies were conducted on extracellular
      matrix or pericellular HA, and the role of circulating HA in vivo has not been
      studied. HA is rapidly cleared from the bloodstream. The scavenger receptor
      Stabilin-2 (Stab2) is considered a major clearance receptor for HA. Here we
      report a dramatic elevation in circulating HA levels in Stab2-deficient mice
      without any overt phenotype. Surprisingly, the metastasis of B16F10 melanoma
      cells to the lungs was markedly suppressed in the Stab2-deficient mice, whereas
      cell proliferation was not affected. Furthermore, administration of an anti-Stab2
      antibody in Stab2(+) mice elevated serum HA levels and prevented the metastasis
      of melanoma to the lung, and also suppressed spontaneous metastasis of mammary
      tumor and human breast tumor cells inoculated in the mammary gland.
      Administration of the antibody or high-dose HA in mice blocked the lodging of
      melanoma cells to the lungs. Furthermore, HA at high concentrations inhibited the
      rolling/tethering of B16 cells to lung endothelial cells. These results suggest
      that blocking Stab2 function prevents tumor metastasis by elevating circulating
      HA levels. Stab2 may be a potential target in antitumor therapy.

PMID- 22371577
TI  - Cyprus as a degraded landscape or resilient environment in the wake of colonial
      intrusion.
AB  - Concerns about global warming, degradation of fragile ecosystems, and
      environmental and societal collapse have increased interest for lessons and/or
      solutions for today's environmental issues. Popular writers have turned to a
      classic degradation thesis of deforestation and presumed desertification within
      the Eastern Mediterranean as a cautionary tale of how past societies have
      committed ecological suicide. However, degradation and/or collapse is far more
      complex than the thesis permits, and uncritical adoption of such simplified
      stories encourages continued use of inaccurate assumptions about human
      environment interaction. In Cyprus, such a degradation story materialized 150 y
      ago, and its promoters aimed to impress on readers their responsibility to
      reverse past environmental mistakes. Both the British Colonial authorities (1878
      1960) and the post-Independence Cypriot government used it to justify their
      environmental policies. Unfortunately, this thesis was formed around several
      misunderstandings about Cypriot environments and society: (i) judgment of
      degradation without appropriate consideration of the difference between
      degradation and change; (ii) oversimplified representation of ruling powers and
      those people ruled; and (iii) denigration of the shepherd lifestyle and its
      presumed environmental impact. A multimethod approach using archival and field
      research offers a more nuanced understanding of the complexity of human
      environment interaction, the underappreciated environmental and societal
      resilience of areas classified as degraded, and the importance of placing events
      within changing socioeconomic and political contexts. This study of natural
      resource management and environmental resilience illustrates that the practices
      that the colonial government viewed as unsustainable likely were sustainable.

PMID- 22371576
TI  - Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release
      via growth hormone-induced ERK hyperactivation, which contributes to short
      stature.
AB  - Noonan syndrome (NS), a genetic disease caused in half of cases by activating
      mutations of the tyrosine phosphatase SHP2 (PTPN11), is characterized by
      congenital cardiopathies, facial dysmorphic features, and short stature. How
      mutated SHP2 induces growth retardation remains poorly understood. We report here
      that early postnatal growth delay is associated with low levels of insulin-like
      growth factor 1 (IGF-1) in a mouse model of NS expressing the D61G mutant of
      SHP2. Conversely, inhibition of SHP2 expression in growth hormone (GH)-responsive
      cell lines results in increased IGF-1 release upon GH stimulation. SHP2-deficient
      cells display decreased ERK1/2 phosphorylation and rat sarcoma (RAS) activation
      in response to GH, whereas expression of NS-associated SHP2 mutants results in
      ERK1/2 hyperactivation in vitro and in vivo. RAS/ERK1/2 inhibition in SHP2
      deficient cells correlates with impaired dephosphorylation of the adaptor Grb2
      associated binder-1 (GAB1) on its RAS GTPase-activating protein (RASGAP) binding
      sites and is rescued by interfering with RASGAP recruitment or function. We
      demonstrate that inhibition of ERK1/2 activation results in an increase of IGF-1
      levels in vitro and in vivo, which is associated with significant growth
      improvement in NS mice. In conclusion, NS-causing SHP2 mutants inhibit GH-induced
      IGF-1 release through RAS/ERK1/2 hyperactivation, a mechanism that could
      contribute to growth retardation. This finding suggests that, in addition to its
      previously shown beneficial effect on NS-linked cardiac and craniofacial defects,
      RAS/ERK1/2 modulation could also alleviate the short stature phenotype in NS
      caused by PTPN11 mutations.

PMID- 22371578
TI  - Strong relationship between elemental stoichiometry and metabolome in plants.
AB  - Shifts in the elemental stoichiometry of organisms in response to their ontogeny
      and to changing environmental conditions should be related to metabolomic changes
      because elements operate mostly as parts of molecular compounds. Here we show
      this relationship in leaves of Erica multiflora throughout their seasonal
      development and in response to moderate experimental field conditions of drought
      and warming. The N/P ratio in leaves decreased in the metabolically active
      growing seasons, coinciding with an increase in the content of primary
      metabolites. These results support the growth-rate hypothesis that states that
      rapidly growing organisms present low N/P ratios because of the increase in
      allocation of P to RNA. The foliar N/K and P/K ratios were lower in summer and in
      the drought treatment, in accordance with the role of K in osmotic protection,
      and coincided with the increase of compounds related to the avoidance of water
      stress. These results provide strong evidence of the relationship between the
      changes in foliar C/N/P/K stoichiometry and the changes in the leaf's metabolome
      during plant growth and environmental stress. Thus these results represent a step
      in understanding the relationships between stoichiometry and an organism's
      lifestyle.

PMID- 22371579
TI  - Collapse, environment, and society.
AB  - Historical collapse of ancient states poses intriguing social-ecological
      questions, as well as potential applications to global change and contemporary
      strategies for sustainability. Five Old World case studies are developed to
      identify interactive inputs, triggers, and feedbacks in devolution. Collapse is
      multicausal and rarely abrupt. Political simplification undermines traditional
      structures of authority to favor militarization, whereas disintegration is
      preconditioned or triggered by acute stress (insecurity, environmental or
      economic crises, famine), with breakdown accompanied or followed by demographic
      decline. Undue attention to stressors risks underestimating the intricate
      interplay of environmental, political, and sociocultural resilience in limiting
      the damages of collapse or in facilitating reconstruction. The conceptual model
      emphasizes resilience, as well as the historical roles of leaders, elites, and
      ideology. However, a historical model cannot simply be applied to contemporary
      problems of sustainability without adjustment for cumulative information and
      increasing possibilities for popular participation. Between the 14th and 18th
      centuries, Western Europe responded to environmental crises by innovation and
      intensification; such modernization was decentralized, protracted, flexible, and
      broadly based. Much of the current alarmist literature that claims to draw from
      historical experience is poorly focused, simplistic, and unhelpful. It fails to
      appreciate that resilience and readaptation depend on identified options,
      improved understanding, cultural solidarity, enlightened leadership, and
      opportunities for participation and fresh ideas.

PMID- 22371580
TI  - Critical perspectives on historical collapse.
AB  - Historical collapse of ancient states or civilizations has raised new awareness
      about its possible relevance to current issues of sustainability, in the context
      of global change. This Special Feature examines 12 case studies of societies
      under stress, of which seven suffered severe transformation. Outcomes were
      complex and unpredictable. Five others overcame breakdown through environmental,
      political, or socio-cultural resilience, which deserves as much attention as the
      identification of stressors. Response to environmental crises of the last
      millennium varied greatly according to place and time but drew from traditional
      knowledge to evaluate new information or experiment with increasing flexibility,
      even if modernization or intensification were decentralized and protracted.
      Longer-term diachronic experience offers insight into how societies have dealt
      with acute stress, a more instructive perspective for the future than is offered
      by apocalyptic scenarios.

PMID- 22371581
TI  - Evolution in coyotes (Canis latrans) in response to the megafaunal extinctions.
AB  - Living coyotes modify their behavior in the presence of larger carnivores, such
      as wolves. However, little is known about the effects of competitor presence or
      absence on morphological change in coyotes or wolves over long periods of time.
      We examined the evolution of coyotes and wolves through time from the late
      Pleistocene, during which many large carnivorous species coexisted as predators
      and competitors, to the Recent; this allowed us to investigate evolutionary
      changes in these species in response to climate change and megafaunal extinctions
      at the end of the Pleistocene. We measured postcranial skeletal morphologies of
      wolves (Canis lupus) and coyotes (C. latrans) from Pleistocene-aged tar deposits,
      as well as early, mid, and recent Holocene populations of both. We found few
      morphological differences between Pleistocene and Holocene wolf populations.
      Conversely, we found many differences in coyotes: Pleistocene coyotes were larger
      and more robust than Holocene populations. However, within 1,000 y of the
      megafaunal extinctions, coyotes are morphologically indistinguishable from modern
      populations. We cannot attribute these differences directly to climate change
      because modern coyotes do not follow Bergmann's rule, which states body size
      increases with decreasing temperature. Instead, we suggest that Pleistocene
      coyotes may have been larger and more robust in response to larger competitors
      and a larger-bodied prey base. Although we cannot separate competition from
      predator-prey interactions, this study indicates that the effects of biotic
      interactions can be detected in the fossil record.

PMID- 22371582
TI  - Neuronal activity in the primate dorsomedial prefrontal cortex contributes to
      strategic selection of response tactics.
AB  - The functional roles of the primate posterior medial prefrontal cortex have
      remained largely unknown. Here, we show that this region participates in the
      regulation of actions in the presence of multiple response tactics. Monkeys
      performed a forelimb task in which a visual cue required prompt decision of
      reaching to a left or a right target. The location of the cue was either
      ipsilateral (concordant) or contralateral (discordant) to the target. As a result
      of extensive training, the reaction times for the concordant and discordant
      trials were indistinguishable, indicating that the monkeys developed tactics to
      overcome the cue-response conflict. Prefrontal neurons exhibited prominent
      activity when the concordant and discordant trials were randomly presented,
      requiring rapid selection of a response tactic (reach toward or away from the
      cue). The following findings indicate that these neurons are involved in the
      selection of tactics, rather than the selection of action or monitoring of
      response conflict: (i) The response period activity of neurons in this region
      disappeared when the monkeys performed the task under the behavioral condition
      that required a single tactic alone, whereas the action varied across trials.
      (ii) The neuronal activity was found in the dorsomedial prefrontal cortex but not
      in the anterior cingulate cortex that has been implicated for the response
      conflict monitoring. These results suggest that the medial prefrontal cortex
      participates in the selection of a response tactic that determines an appropriate
      action. Furthermore, the observation of dynamic, task-dependent neuronal activity
      necessitates reconsideration of the conventional concept of cortical motor
      representation.

PMID- 22371583
TI  - Multiple self-splicing introns in the 16S rRNA genes of giant sulfur bacteria.
AB  - The gene encoding the small subunit rRNA serves as a prominent tool for the
      phylogenetic analysis and classification of Bacteria and Archaea owing to its
      high degree of conservation and its fundamental function in living organisms.
      Here we show that the 16S rRNA genes of not-yet-cultivated large sulfur bacteria,
      among them the largest known bacterium Thiomargarita namibiensis, regularly
      contain numerous self-splicing introns of variable length. The 16S rRNA genes can
      thus be enlarged to up to 3.5 kb. Remarkably, introns have never been identified
      in bacterial 16S rRNA genes before, although they are the most frequently
      sequenced genes today. This may be caused in part by a bias during the PCR
      amplification step that discriminates against longer homologs, as we show
      experimentally. Such length heterogeneity of 16S rRNA genes has so far never been
      considered when constructing 16S rRNA-based clone libraries, even though an
      elongation of rRNA genes due to intervening sequences has been reported
      previously. The detection of elongated 16S rRNA genes has profound implications
      for common methods in molecular ecology and may cause systematic biases in
      several techniques. In this study, catalyzed reporter deposition-fluorescence in
      situ hybridization on both ribosomes and rRNA precursor molecules as well as in
      vitro splicing experiments were performed and confirmed self-splicing of the
      introns. Accordingly, the introns do not inhibit the formation of functional
      ribosomes.

PMID- 22371584
TI  - Calcium influx-mediated signaling is required for complete mouse egg activation.
AB  - Mammalian fertilization is accompanied by oscillations in egg cytoplasmic calcium
      (Ca(2+)) concentrations that are critical for completion of egg activation. These
      oscillations are initiated by Ca(2+) release from inositol 1,4,5-trisphosphate
      (IP(3))-sensitive intracellular stores. We tested the hypothesis that Ca(2+)
      influx across the plasma membrane was a requisite component of egg activation
      signaling, and not simply a Ca(2+) source for store repletion. Using
      intracytoplasmic sperm injection (ICSI) and standard in vitro fertilization
      (IVF), we found that Ca(2+) influx was not required to initiate resumption of
      meiosis II. However, even if multiple oscillations in intracellular Ca(2+)
      occurred, in the absence of Ca(2+) influx, the fertilized eggs failed to emit the
      second polar body, resulting in formation of three pronuclei. Additional
      experiments using the Ca(2+) chelator, BAPTA/AM, demonstrated that Ca(2+) influx
      is sufficient to support polar body emission and pronucleus formation after only
      a single sperm-induced Ca(2+) transient, whereas BAPTA/AM-treated ICSI or
      fertilized eggs cultured in Ca(2+)-free medium remained arrested in metaphase II.
      Inhibition of store-operated Ca(2+) entry had no effect on ICSI-induced egg
      activation, so Ca(2+) influx through alternative channels must participate in egg
      activation signaling. Ca(2+) influx appears to be upstream of CaMKIIgamma
      activity because eggs can be parthenogenetically activated with a constitutively
      active form of CaMKIIgamma in the absence of extracellular Ca(2+). These results
      suggest that Ca(2+) influx at fertilization not only maintains Ca(2+)
      oscillations by replenishing Ca(2+) stores, but also activates critical signaling
      pathways upstream of CaMKIIgamma that are required for second polar body
      emission.

PMID- 22371585
TI  - Higher social class predicts increased unethical behavior.
AB  - Seven studies using experimental and naturalistic methods reveal that upper-class
      individuals behave more unethically than lower-class individuals. In studies 1
      and 2, upper-class individuals were more likely to break the law while driving,
      relative to lower-class individuals. In follow-up laboratory studies, upper-class
      individuals were more likely to exhibit unethical decision-making tendencies
      (study 3), take valued goods from others (study 4), lie in a negotiation (study
      5), cheat to increase their chances of winning a prize (study 6), and endorse
      unethical behavior at work (study 7) than were lower-class individuals. Mediator
      and moderator data demonstrated that upper-class individuals' unethical
      tendencies are accounted for, in part, by their more favorable attitudes toward
      greed.

PMID- 22371586
TI  - Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically
      activated, oxygen-generating biomaterials.
AB  - A major hindrance in engineering tissues containing highly metabolically active
      cells is the insufficient oxygenation of these implants, which results in dying
      or dysfunctional cells in portions of the graft. The development of methods to
      increase oxygen availability within tissue-engineered implants, particularly
      during the early engraftment period, would serve to allay hypoxia-induced cell
      death. Herein, we designed and developed a hydrolytically activated oxygen
      generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated
      solid calcium peroxide, PDMS-CaO(2). Encapsulation of solid peroxide within
      hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk
      generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The
      ability of this oxygen-generating material to support cell survival was evaluated
      using a beta cell line and pancreatic rat islets. The presence of a single PDMS
      CaO(2) disk eliminated hypoxia-induced cell dysfunction and death for both cell
      types, resulting in metabolic function and glucose-dependent insulin secretion
      comparable to that in normoxic controls. A single PDMS-CaO(2) disk also sustained
      enhanced beta cell proliferation for more than 3 wk under hypoxic culture
      conditions. Incorporation of these materials within 3D constructs illustrated the
      benefits of these materials to prevent the development of detrimental oxygen
      gradients within large implants. Mathematical simulations permitted accurate
      prediction of oxygen gradients within 3D constructs and highlighted conditions
      under which supplementation of oxygen tension would serve to benefit cellular
      viability. Given the generality of this platform, the translation of these
      materials to other cell-based implants, as well as ischemic tissues in general,
      is envisioned.

PMID- 22371587
TI  - QnAs with Michael S. Gazzaniga. Interview by Prashant Nair.

PMID- 22371588
TI  - A distinct lineage of influenza A virus from bats.
AB  - Influenza A virus reservoirs in animals have provided novel genetic elements
      leading to the emergence of global pandemics in humans. Most influenza A viruses
      circulate in waterfowl, but those that infect mammalian hosts are thought to pose
      the greatest risk for zoonotic spread to humans and the generation of pandemic or
      panzootic viruses. We have identified an influenza A virus from little yellow
      shouldered bats captured at two locations in Guatemala. It is significantly
      divergent from known influenza A viruses. The HA of the bat virus was estimated
      to have diverged at roughly the same time as the known subtypes of HA and was
      designated as H17. The neuraminidase (NA) gene is highly divergent from all known
      influenza NAs, and the internal genes from the bat virus diverged from those of
      known influenza A viruses before the estimated divergence of the known influenza
      A internal gene lineages. Attempts to propagate this virus in cell cultures and
      chicken embryos were unsuccessful, suggesting distinct requirements compared with
      known influenza viruses. Despite its divergence from known influenza A viruses,
      the bat virus is compatible for genetic exchange with human influenza viruses in
      human cells, suggesting the potential capability for reassortment and
      contributions to new pandemic or panzootic influenza A viruses.

PMID- 22371589
TI  - RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is an RNA-dominant disease caused by abnormal
      transcripts containing expanded CUG repeats. The CUG transcripts aggregate in the
      nucleus to form RNA foci and lead to nuclear depletion of Muscleblind-like 1
      (MBNL1) and stabilized expression of CUGBP Elav like family 1 (CELF1), both of
      which are splicing regulatory proteins. The imbalance of these proteins results
      in misregulation of alternative splicing and neuromuscular abnormalities. Here,
      we report the use of antisense oligonucleotides (ASOs) as a therapeutic approach
      to target the pathogenic RNA in DM1. We designed chimeric ASOs, termed gapmers,
      containing modified nucleic acid residues to induce RNase H-mediated degradation
      of CUG-repeat transcripts. The gapmers selectively knockdown expanded CUG
      transcripts and are sufficient to disrupt RNA foci both in cell culture and mouse
      models for DM1. Furthermore, combination of gapmers with morpholino ASOs that
      help release binding of MBNL1 to the toxic RNA can potentially enhance the
      knockdown effect. Additional optimization will be required for systemic delivery;
      however, our study provides an alternative strategy for the use of ASOs in DM1
      therapy.

PMID- 22371590
TI  - Adaptive coding of reward prediction errors is gated by striatal coupling.
AB  - To efficiently represent all of the possible rewards in the world, dopaminergic
      midbrain neurons dynamically adapt their coding range to the momentarily
      available rewards. Specifically, these neurons increase their activity for an
      outcome that is better than expected and decrease it for an outcome worse than
      expected, independent of the absolute reward magnitude. Although this adaptive
      coding is well documented, it remains unknown how this rescaling is implemented.
      To investigate the adaptive coding of prediction errors and its underlying
      rescaling process, we used human functional magnetic resonance imaging (fMRI) in
      combination with a reward prediction task that involved different reward
      magnitudes. We demonstrate that reward prediction errors in the human striatum
      are expressed according to an adaptive coding scheme. Strikingly, we show that
      adaptive coding is gated by changes in effective connectivity between the
      striatum and other reward-sensitive regions, namely the midbrain and the medial
      prefrontal cortex. Our results provide evidence that striatal prediction errors
      are normalized by a magnitude-dependent alteration in the interregional
      connectivity within the brain's reward system.

PMID- 22371591
TI  - Climate change, adaptive cycles, and the persistence of foraging economies during
      the late Pleistocene/Holocene transition in the Levant.
AB  - Climatic forcing during the Younger Dryas (~12.9-11.5 ky B.P.) event has become
      the theoretical basis to explain the origins of agricultural lifestyles in the
      Levant by suggesting a failure of foraging societies to adjust. This explanation
      however, does not fit the scarcity of data for predomestication cultivation in
      the Natufian Period. The resilience of Younger Dryas foragers is better
      illustrated by a concept of adaptive cycles within a theory of adaptive change
      (resilience theory). Such cycles consist of four phases: release/collapse
      (Omega); reorganization (alpha), when the system restructures itself after a
      catastrophic stimulus through innovation and social memory--a period of greater
      resilience and less vulnerability; exploitation (r); and conservation (K),
      representing an increasingly rigid system that loses flexibility to change. The
      Kebarans and Late Natufians had similar responses to cold and dry conditions vs.
      Early Natufians and the Pre-Pottery Neolithic A responses to warm and wet
      climates. Kebarans and Late Natufians (alpha-phase) shifted to a broader-based
      diet and increased their mobility. Early Natufian and Pre-Pottery Neolithic A
      populations (r- and K-phases) had a growing investment in more narrowly focused,
      high-yield plant resources, but they maintained the broad range of hunted animals
      because of increased sedentism. These human adaptive cycles interlocked with
      plant and animal cycles. Forest and grassland vegetation responded to late
      Pleistocene and early Holocene climatic fluctuations, but prey animal cycles
      reflected the impact of human hunting pressure. The combination of these three
      adaptive cycles results in a model of human adaptation, showing potential for
      great sustainability of Levantine foraging systems even under adverse climatic
      conditions.

PMID- 22371592
TI  - Axonal transport deficits and degeneration can evolve independently in mouse
      models of amyotrophic lateral sclerosis.
AB  - Axonal transport deficits have been reported in many neurodegenerative conditions
      and are widely assumed to be an immediate causative step of axon and synapse
      loss. By imaging changes in axonal morphology and organelle transport over time
      in several animal models of amyotrophic lateral sclerosis (ALS), we now find that
      deficits in axonal transport of organelles (mitochondria, endosomes) and axon
      degeneration can evolve independently. This conclusion rests on the following
      results: (i) Axons can survive despite long-lasting transport deficits: In the
      SOD(G93A) model of ALS, transport deficits are detected soon after birth, months
      before the onset of axon degeneration. (ii) Transport deficits are not necessary
      for axon degeneration: In the SOD(G85R) model of ALS, motor axons degenerate, but
      transport is unaffected. (iii) Axon transport deficits are not sufficient to
      cause immediate degeneration: In mice that overexpress wild-type superoxide
      dismutase-1 (SOD(WT)), axons show chronic transport deficits, but survive. These
      data suggest that disturbances of organelle transport are not a necessary step in
      the emergence of motor neuron degeneration.

PMID- 22371593
TI  - Adaptive horizontal transfer of a bacterial gene to an invasive insect pest of
      coffee.
AB  - Horizontal gene transfer (HGT) involves the nonsexual transmission of genetic
      material across species boundaries. Although often detected in prokaryotes,
      examples of HGT involving animals are relatively rare, and any evolutionary
      advantage conferred to the recipient is typically obscure. We identified a gene
      (HhMAN1) from the coffee berry borer beetle, Hypothenemus hampei, a devastating
      pest of coffee, which shows clear evidence of HGT from bacteria. HhMAN1 encodes a
      mannanase, representing a class of glycosyl hydrolases that has not previously
      been reported in insects. Recombinant HhMAN1 protein hydrolyzes coffee berry
      galactomannan, the major storage polysaccharide in this species and the presumed
      food of H. hampei. HhMAN1 was found to be widespread in a broad biogeographic
      survey of H. hampei accessions, indicating that the HGT event occurred before
      radiation of the insect from West Africa to Asia and South America. However, the
      gene was not detected in the closely related species H. obscurus (the tropical
      nut borer or "false berry borer"), which does not colonize coffee beans. Thus,
      HGT of HhMAN1 from bacteria represents a likely adaptation to a specific
      ecological niche and may have been promoted by intensive agricultural practices.

PMID- 22371594
TI  - Cultural adaptation, compounding vulnerabilities and conjunctures in Norse
      Greenland.
AB  - Norse Greenland has been seen as a classic case of maladaptation by an inflexible
      temperate zone society extending into the arctic and collapse driven by climate
      change. This paper, however, recognizes the successful arctic adaptation achieved
      in Norse Greenland and argues that, although climate change had impacts, the end
      of Norse settlement can only be truly understood as a complex socioenvironmental
      system that includes local and interregional interactions operating at different
      geographic and temporal scales and recognizes the cultural limits to adaptation
      of traditional ecological knowledge. This paper is not focused on a single
      discovery and its implications, an approach that can encourage monocausal and
      environmentally deterministic emphasis to explanation, but it is the product of
      sustained international interdisciplinary investigations in Greenland and the
      rest of the North Atlantic. It is based on data acquisitions, reinterpretation of
      established knowledge, and a somewhat different philosophical approach to the
      question of collapse. We argue that the Norse Greenlanders created a flexible and
      successful subsistence system that responded effectively to major environmental
      challenges but probably fell victim to a combination of conjunctures of large
      scale historic processes and vulnerabilities created by their successful prior
      response to climate change. Their failure was an inability to anticipate an
      unknowable future, an inability to broaden their traditional ecological knowledge
      base, and a case of being too specialized, too small, and too isolated to be able
      to capitalize on and compete in the new protoworld system extending into the
      North Atlantic in the early 15th century.

PMID- 22371595
TI  - Honesty mediates the relationship between serotonin and reaction to unfairness.
AB  - How does one deal with unfair behaviors? This subject has long been investigated
      by various disciplines including philosophy, psychology, economics, and biology.
      However, our reactions to unfairness differ from one individual to another.
      Experimental economics studies using the ultimatum game (UG), in which players
      must decide whether to accept or reject fair or unfair offers, have also shown
      that there are substantial individual differences in reaction to unfairness.
      However, little is known about psychological as well as neurobiological
      mechanisms of this observation. We combined a molecular imaging technique, an
      economics game, and a personality inventory to elucidate the neurobiological
      mechanism of heterogeneous reactions to unfairness. Contrary to the common belief
      that aggressive personalities (impulsivity or hostility) are related to the high
      rejection rate of unfair offers in UG, we found that individuals with apparently
      peaceful personalities (straightforwardness and trust) rejected more often and
      were engaged in personally costly forms of retaliation. Furthermore, individuals
      with a low level of serotonin transporters in the dorsal raphe nucleus (DRN) are
      honest and trustful, and thus cannot tolerate unfairness, being candid in
      expressing their frustrations. In other words, higher central serotonin
      transmission might allow us to behave adroitly and opportunistically, being good
      at playing games while pursuing self-interest. We provide unique neurobiological
      evidence to account for individual differences of reaction to unfairness.

PMID- 22371596
TI  - Development of GABAergic inputs controls the contribution of maturing neurons to
      the adult hippocampal network.
AB  - New neurons are continuously generated in the dentate gyrus (DG) in the adult
      hippocampus, and new granule cells (GCs) have been shown to be necessary for
      several aspects of learning and memory. Nonetheless, the limited information
      available regarding the anatomical and physiological development of synaptic
      inputs onto maturing neurons has restricted our understanding of how new GCs
      affect cognition. Here, we use photostimulation to demonstrate the time course by
      which anatomically isolated inhibitory inputs develop onto maturing GCs. We then
      show that the gradual development of inhibition is sufficient in a computational
      model to drive learning of novel information in young neurons. Finally, we
      validate this model observation by using slice physiology to show how inhibition
      regulates firing probability and plasticity in young GCs. Combined, these data
      demonstrate that the unique connectivity of immature GCs affords them a
      functional role that is different from mature neurons in the DG circuit, a
      distinction that potentially underlies many of the proposed functions of new
      neurons in the hippocampal network.

PMID- 22371597
TI  - Choristers of the Jurassic.

PMID- 22371598
TI  - Phylogenetic differences in calcium permeability of the auditory hair cell
      cholinergic nicotinic receptor.
AB  - The alpha9 and alpha10 cholinergic nicotinic receptor subunits assemble to form
      the receptor that mediates efferent inhibition of hair cell function within the
      auditory sensory organ, a mechanism thought to modulate the dynamic range of
      hearing. In contrast to all nicotinic receptors, which serve excitatory
      neurotransmission, the activation of alpha9alpha10 produces hyperpolarization of
      hair cells. An evolutionary analysis has shown that the alpha10 subunit exhibits
      signatures of positive selection only along the mammalian lineage, strongly
      suggesting the acquisition of a unique function. To establish whether mammalian
      alpha9alpha10 receptors have acquired distinct functional properties as a
      consequence of this evolutionary pressure, we compared the properties of rat and
      chicken recombinant and native alpha9alpha10 receptors. Our main finding in the
      present work is that, in contrast to the high (pCa(2+)/pMonovalents ~10) Ca(2+)
      permeability reported for rat alpha9alpha10 receptors, recombinant and native
      chicken alpha9alpha10 receptors have a much lower permeability (~2) to this
      cation, comparable to that of neuronal alpha4beta2 receptors. Moreover, we show
      that, in contrast to alpha10, alpha7 as well as alpha4 and beta2 nicotinic
      subunits are under purifying selection in vertebrates, consistent with the
      conserved Ca(2+) permeability reported across species. These results have
      important consequences for the activation of signaling cascades that lead to
      hyperpolarization of hair cells after alpha9alpha10 gating at the cholinergic
      hair cell synapse. In addition, they suggest that high Ca(2+) permeability of the
      alpha9alpha10 cholinergic nicotinic receptor might have evolved together with
      other features that have given the mammalian ear an expanded high-frequency
      sensitivity.

PMID- 22371599
TI  - Rapid creation of Arabidopsis doubled haploid lines for quantitative trait locus
      mapping.
AB  - Quantitative trait loci (QTL) mapping is a powerful tool for investigating the
      genetic basis of natural variation. QTL can be mapped using a number of different
      population designs, but recombinant inbred lines (RILs) are among the most
      effective. Unfortunately, homozygous RIL populations are time consuming to
      construct, typically requiring at least six generations of selfing starting from
      a heterozygous F(1). Haploid plants produced from an F(1) combine the two
      parental genomes and have only one allele at every locus. Converting these
      sterile haploids into fertile diploids (termed "doubled haploids," DHs) produces
      immortal homozygous lines in only two steps. Here we describe a unique technique
      for rapidly creating recombinant doubled haploid populations in Arabidopsis
      thaliana: centromere-mediated genome elimination. We generated a population of
      238 doubled haploid lines that combine two parental genomes and genotyped them by
      reduced representation Illumina sequencing. The recombination rate and parental
      allele frequencies in our population are similar to those found in existing RIL
      sets. We phenotyped this population for traits related to flowering time and for
      petiole length and successfully mapped QTL controlling each trait. Our work
      demonstrates that doubled haploid populations offer a rapid, easy alternative to
      RILs for Arabidopsis genetic analysis.

PMID- 22371600
TI  - Trafficking of protein into the recently established photosynthetic organelles of
      Paulinella chromatophora.
AB  - Endosymbiotic acquisition of bacteria by a protist, with subsequent evolution of
      the bacteria into mitochondria and plastids, had a transformative impact on
      eukaryotic biology. Reconstructing events that created a stable association
      between endosymbiont and host during the process of organellogenesis--including
      establishment of regulated protein import into nascent organelles--is difficult
      because they date back more than 1 billion years. The amoeba Paulinella
      chromatophora contains nascent photosynthetic organelles of more recent
      evolutionary origin (~60 Mya) termed chromatophores (CRs). After the initial
      endosymbiotic event, the CR genome was reduced to approximately 30% of its
      presumed original size and more than 30 expressed genes were transferred from the
      CR to the amoebal nuclear genome. Three transferred genes--psaE, psaK1, and psaK2
      -encode subunits of photosystem I. Here we report biochemical evidence that PsaE,
      PsaK1, and PsaK2 are synthesized in the amoeba cytoplasm and traffic into CRs,
      where they assemble with CR-encoded subunits into photosystem I complexes.
      Additionally, our data suggest that proteins routed to CRs pass through the Golgi
      apparatus. Whereas genome reduction and transfer of genes from bacterial to host
      genome have been reported to occur in other obligate bacterial endosymbioses,
      this report outlines the import of proteins encoded by such transferred genes
      into the compartment derived from the bacterial endosymbiont. Our study showcases
      P. chromatophora as an exceptional model in which to study early events in
      organellogenesis, and suggests that protein import into bacterial endosymbionts
      might be a phenomenon much more widespread than currently assumed.

PMID- 22371601
TI  - Plague and landscape resilience in premodern Iceland.
AB  - In debates on societal collapse, Iceland occupies a position of precarious
      survival, defined by not becoming extinct, like Norse Greenland, but having
      endured, sometimes by the narrowest of margins. Classic decline narratives for
      late medieval to early modern Iceland stress compounding adversities, where
      climate, trade, political domination, unsustainable practices, and environmental
      degradation conspire with epidemics and volcanism to depress the Icelanders and
      turn the once-proud Vikings and Saga writers into one of Europe's poorest
      nations. A mainstay of this narrative is the impact of incidental setbacks such
      as plague and volcanism, which are seen to have compounded and exacerbated
      underlying structural problems. This research shows that this view is not
      correct. We present a study of landscape change that uses 15 precisely dated
      tephra layers spanning the whole 1,200-y period of human settlement in Iceland.
      These tephras have provided 2,625 horizons of known age within 200 stratigraphic
      sections to form a high-resolution spatial and temporal record of change. This
      finding shows short-term (50 y) declines in geomorphological activity after two
      major plagues in A.D. 15th century, variations that probably mirrored variations
      in the population. In the longer term, the geomorphological impact of climate
      changes from the 14th century on is delayed, and landscapes (as well as Icelandic
      society) exhibit resilience over decade to century timescales. This finding is
      not a simple consequence of depopulation but a reflection of how Icelandic
      society responded with a scaling back of their economy, conservation of core
      functionality, and entrenchment of the established order.

PMID- 22371602
TI  - Systematic identification of type I and type II interferon-induced antiviral
      factors.
AB  - Type I and type II interferons (IFNs) are cytokines that establish the cellular
      antiviral state through the induction of IFN-stimulated genes (ISGs). We sought
      to understand the basis of the antiviral activity induced by type I and II IFNs
      in relation to the functions of their ISGs. Based on gene expression studies, we
      systematically identified antiviral ISGs by performing blinded, functional
      screens on 288 type I and type II ISGs. We assessed and validated the antiviral
      activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV),
      and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34
      ISGs that elicited an antiviral effect on the replication of either one or both
      viruses. Fourteen ISGs have uncharacterized antiviral functions. We further
      defined ISGs that affect critical life-cycle processes in expression of VSV
      protein and MHV-68 immediate-early genes. Two previously undescribed antiviral
      ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more
      susceptible to VSV infection but less so to MHV-68 infection. On the other hand,
      exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These
      results delineate common and distinct sets of type I and type II IFN-induced
      genes as well as identify unique ISGs that have either broad or specific
      antiviral effects on these viruses.

PMID- 22371604
TI  - A cold oceanographic regime with high exploitation rates in the Northeast Pacific
      forecasts a collapse of the sardine stock.
AB  - The oceanographic conditions in the north Pacific have shifted to a colder
      period, Pacific sardine (Sardinops sagax) biomass has declined precipitously in
      the California Current, the international sardine fishery is collapsing, and
      mackerel (Trachurus symmetricus and Scomber japonicus) are thriving. This
      situation occurred in the mid-1900s, but indices of current oceanographic
      conditions and the results of our acoustic-trawl surveys indicate it likely is
      recurring now, perhaps with similar socioeconomic and ecological consequences.
      Also alarming is the repetition of the fishery's response to a declining sardine
      stock-progressively higher exploitation rates targeting the oldest, largest, and
      most fecund fish. Furthermore, our data indicate the recent reproductive
      condition of sardine is poor, and their productivity is below modeled estimates
      used to derive the current fishery-exploitation rates. Consequently, the sardine
      population has been reduced to two cohorts that are unlikely to produce an
      appreciable new cohort. Thus, a near-term recovery of this important stock is
      unlikely, depending on the return of warmer oceanographic conditions, reduced
      pressure from mackerel species, and perhaps the adoption of a more precautionary
      strategy for managing the residual sardine population.

PMID- 22371603
TI  - Primary epimutations introduced during intracytoplasmic sperm injection (ICSI)
      are corrected by germline-specific epigenetic reprogramming.
AB  - The use of assisted reproductive technologies (ART) has become increasingly
      common worldwide and is now responsible for 2-3% of children born in developed
      countries. Multiple reports have suggested that ART-conceived children are more
      likely to develop rare epigenetic disorders such as Beckwith-Wiedemann Syndrome
      or Angelman Syndrome, both of which involve dysregulation of imprinted genes.
      Anecdotal reports suggest that animals produced with ART that manifest apparent
      epigenetic defects typically do not transmit these epimutations to subsequent
      generations when allowed to breed naturally, but this hypothesis has not been
      directly studied. We analyzed allele-specific DNA methylation and expression at
      three imprinted genes, H19, Snrpn, and Peg3, in somatic cells from adult mice
      generated with the use of intracytoplasmic sperm injection (ICSI), a type of ART.
      Epimutations were detected in most of the ICSI-derived mice, but not in somatic
      cells of their offspring produced by natural mating. We examined germ cells from
      the ICSI mice that exhibited epimutations in their somatic cells and confirmed
      normal epigenetic reprogramming of the three imprinted genes analyzed.
      Collectively, these results confirm that ART procedures can lead to the formation
      of primary epimutations, but while such epimutations are likely to be maintained
      indefinitely in somatic cells of the ART-derived individuals, they are normally
      corrected in the germ line by epigenetic reprogramming and thus, not propagated
      to subsequent generations.

PMID- 22371605
TI  - Wetland fields as mirrors of drought and the Maya abandonment.
AB  - Getting at the Maya Collapse has both temporal and geographic dimensions, because
      it occurred over centuries and great distances. This requires a wide range of
      research sites and proxy records, ranging from lake cores to geomorphic evidence,
      such as stratigraphy and speleothems. This article synthesizes these lines of
      evidence, together with previously undescribed findings on Maya wetland formation
      and use in a key region near the heart of the central Maya Lowlands. Growing
      lines of evidence point to dryer periods in Maya history, which correlate to
      major periods of transition. The main line of evidence in this paper comes from
      wetland use and formation studies, which show evidence for both large-scale
      environmental change and human adaptation or response. Based on multiproxy
      studies, Maya wetland fields had a long and varied history, but most evidence
      indicates the start of disuse during or shortly after the Maya Terminal Classic.
      Hence, the pervasiveness of collapse extended into a range of wetlands, including
      perennial wetlands, which should have been less responsive to drought as a driver
      of disuse. A synthesis of the lines of evidence for canal infilling shows no
      attempts to reclaim them after the Classic Period.

PMID- 22371607
TI  - Capsular ligaments of the hip: anatomic, histologic, and positional study in
      cadaveric specimens with MR arthrography.
AB  - PURPOSE: To demonstrate the anatomy of the capsular ligaments of the hip by using
      magnetic resonance (MR) arthrography. MATERIALS AND METHODS: Institutional
      policies were followed regarding cadaver use. MR arthrographic images of 10 fresh
      human cadaveric hips were obtained by using a positioning device to arrange the
      hip joint in different controlled positions. MR appearances of the capsular
      structures were noted and correlated with those seen on anatomic slices and
      dissections. Two readers working in consensus graded the visibility of these
      structures. Tissue samples were collected for histologic analysis. An MR
      positional study was performed to evaluate the length of these capsular ligaments
      and the subjective classification of their appearance as either taut or lax in
      extension, flexion, abduction, adduction, and internal and external rotation.
      RESULTS: The hip capsule inserts proximally and continuously to the acetabular
      rim periosteum. Distally, it has a firm anterior insertion at the femoral
      intertrochanteric line and no posterior osseous insertion. The inferior band of
      the iliofemoral ligament was best evaluated in the sagittal, axial, and axial
      oblique planes, and it serves a restrictive function in extension; the superior
      band of the iliofemoral ligament was best evaluated in the coronal and axial
      oblique planes, and it serves a restrictive function in external rotation; the
      ischiofemoral ligament was best evaluated in the axial and axial oblique planes,
      and it serves a restrictive role in internal rotation; the pubofemoral ligament
      was best evaluated in the sagittal plane, and it serves a restrictive function in
      abduction; and the zona orbicularis could be evaluated equally well in any
      imaging plane. CONCLUSION: MR arthrography enables visualization of the capsular
      ligaments of the hip.

PMID- 22371606
TI  - Repressor element-1 silencing transcription factor (REST)-dependent epigenetic
      remodeling is critical to ischemia-induced neuronal death.
AB  - Dysregulation of the transcriptional repressor element-1 silencing transcription
      factor (REST)/neuron-restrictive silencer factor is important in a broad range of
      diseases, including cancer, diabetes, and heart disease. The role of REST
      dependent epigenetic modifications in neurodegeneration is less clear. Here, we
      show that neuronal insults trigger activation of REST and CoREST in a clinically
      relevant model of ischemic stroke and that REST binds a subset of
      "transcriptionally responsive" genes (gria2, grin1, chrnb2, nefh, nfkappab2,
      trpv1, chrm4, and syt6), of which the AMPA receptor subunit GluA2 is a top hit.
      Genes with enriched REST exhibited decreased mRNA and protein. We further show
      that REST assembles with CoREST, mSin3A, histone deacetylases 1 and 2, histone
      methyl-transferase G9a, and methyl CpG binding protein 2 at the promoters of
      target genes, where it orchestrates epigenetic remodeling and gene silencing.
      RNAi-mediated depletion of REST or administration of dominant-negative REST
      delivered directly into the hippocampus in vivo prevents epigenetic
      modifications, restores gene expression, and rescues hippocampal neurons. These
      findings document a causal role for REST-dependent epigenetic remodeling in the
      neurodegeneration associated with ischemic stroke and identify unique therapeutic
      targets for the amelioration of hippocampal injury and cognitive deficits.

PMID- 22371608
TI  - Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of
      silicone stent removal.
AB  - PURPOSE: To evaluate whether air pockets (tracheobronchial air columns in the
      space between the outer surface of the stent and the adjacent airway wall)
      discernible at computed tomography (CT) can help optimize the time of stent
      removal in patients with posttuberculosis tracheobronchial stenosis (PTTS).
      MATERIALS AND METHODS: The study was approved by the institutional review board,
      and informed consent was obtained from all patients. Data from 41 patients (five
      men, 36 women) with a median age of 39 years (range, 21-64 years) who underwent
      silicone stent placement owing to PTTS, followed by CT and stent removal 6-12
      months after clinical stabilization, were investigated retrospectively. Two
      radiologists determined whether the extent of air pockets on CT scans was
      associated with clinical success, which was defined as maintenance of a
      prosthesis-free airway for more than 2 years after stent removal. Radiologic
      features were compared for outcome by using a Wilcoxon two-sample test or Fisher
      exact test. RESULTS: Stents were removed successfully in 31 patients (76%). Air
      pockets longer than 1 cm or longer than 2 cm were associated with successful
      stent removal (P = .04 and P = .006, respectively). The sensitivity and
      specificity of air pocket length in the prediction of successful stent removal
      were 84% and 50%, respectively, for air pockets longer than 1 cm and 68% and 70%
      for air pockets longer than 2 cm. CONCLUSION: The extent of air pockets at chest
      CT shows correlation with the success of stent removal, indicates regression of
      stenosis, and may help guide the optimal time for stent removal.

PMID- 22371609
TI  - Serial CT findings of Mycobacterium massiliense pulmonary disease compared with
      Mycobacterium abscessus disease after treatment with antibiotic therapy.
AB  - PURPOSE: To present the serial computed tomographic (CT) findings of lung
      abnormalities in Mycobacterium massiliense pulmonary disease compared with those
      in Mycobacterium abscessus disease. MATERIALS AND METHODS: The institutional
      review board approved this retrospective study and waived informed consent.
      Serial chest CT scans of M massiliense (n = 34) and M abscessus (n = 24)
      pulmonary diseases were retrospectively reviewed. Patients were treated with
      clarithromycin-containing combination antibiotics regimen, and sputum
      examinations were performed regularly. CT scans were obtained at the beginning of
      antibiotic therapy, at the end of 4-week hospitalization, and at the time of 12
      month antibiotic therapy. RESULTS: All patients with M massiliense disease had
      sputum conversion during treatment, whereas 50% of patients with M abscessus
      disease had sputum conversion. The most common CT findings of M massiliense
      disease at presentation were cellular bronchiolitis (n = 34, 100%),
      bronchiectasis (n = 34, 100%), consolidation (n = 33, 97%), nodules (n = 32,
      94%), and cavities (n = 15, 44%). These findings were similar in M abscessus
      disease. Thirty (88%) patients with M massiliense disease had decrease in overall
      CT score at 12-month therapy, whereas only eight (33%) patients with M abscessus
      disease had a decrease (P < .0001). Improvement was noticeable in cellular
      bronchiolitis and cavity in M massiliense disease. CONCLUSION: Common CT findings
      of M massiliense diseases overlap with those of M abscessus disease. However,
      responses to antibiotic treatment are much different; in M massiliense disease,
      negative sputum conversion is accomplished in all patients and serial CT scans
      show improvement in most patients.

PMID- 22371610
TI  - Dual-source radiofrequency transmission with patient-adaptive local
      radiofrequency shimming for 3.0-T cardiac MR imaging: initial experience.
AB  - PURPOSE: To evaluate the effect of dual-source parallel radiofrequency (RF)
      transmission with patient-adaptive local RF shimming on image quality, image
      contrast, and diagnostic confidence at routine clinical cardiac magnetic
      resonance (MR) imaging with use of a 3.0-T dual-channel transmit whole-body MR
      system. MATERIALS AND METHODS: Written informed consent was obtained from all
      patients, and the study protocol was approved by the local institutional review
      board. Cardiac MR imaging was performed in 28 patients by using a 3.0-T MR unit
      equipped with a dual-source RF transmission system. The effect of conventional
      versus dual-source RF transmission on steady-state free precession (SSFP) cine
      sequences and turbo spin-echo (TSE) black-blood (BB) sequences was evaluated. The
      homogeneity of the B1 field and contrast-to-noise ratios (CNRs) were measured and
      tested for statistical significance with the paired t test. Images were analyzed
      qualitatively for homogeneity, the presence of off-resonance artifacts, and
      diagnostic confidence independently by two readers. Statistical significance was
      assessed with the Wilcoxon signed rank test. Inter- and intraobserver agreement
      was assessed with kappa statistics. RESULTS: Quantitative image analysis revealed
      that B1 homogeneity and CNR were significantly improved for images acquired with
      dual-source RF transmission compared with conventional RF transmission (P =
      .005). The quality of SSFP and TSE BB images of the left and the right ventricles
      showed a significant improvement with respect to image homogeneity and diagnostic
      confidence as evaluated by the readers (P = .0001, kappa > 0.74). As a side
      effect, off-resonance artifacts were significantly reduced on SSFP images (P =
      .0001, kappa > 0.76). CONCLUSION: Dual-source parallel RF transmission
      significantly improves image homogeneity, image contrast, and diagnostic
      confidence compared with conventional RF transmission of cardiac SSFP and TSE BB
      sequences.

PMID- 22371611
TI  - Interregional correlations in Parkinson disease and Parkinson-related dementia
      with resting functional MR imaging.
AB  - PURPOSE: To apply a recently developed native-space (or native-surface) method to
      compare resting functional magnetic resonance (MR) imaging correlations
      (functional connectivity) measured in patients with Parkinson-related dementia
      (PRD) to those measured in cognitively unimpaired, age-matched control subjects
      with or without Parkinson disease (PD). MATERIALS AND METHODS: The study was
      approved by the institutional review board and complied with HIPAA regulations.
      Participants included cognitively unimpaired elderly individuals (n = 19),
      cognitively unimpaired patients with PD (n = 19), and patients with PRD (n = 18).
      Resting functional MR data were assessed by calculating correlation coefficients
      between blood oxygen level-dependent time series of a seed region and of other
      regions of interest selected a priori. Two seeds were used: a medial parietal
      region that contributes to the default network affected in Alzheimer disease and
      the caudate, which is affected by loss of dopaminergic inputs in PD. Correlation
      analyses were performed in the native space of individual subjects to avoid
      confounds from transformation to an average brain. Two-sample t tests were
      applied to data from each native-surface region of interest, and vertex-wise
      comparisons were made by using two-sample t tests at each vertex on the group
      surface; statistical results were corrected for multiple comparisons. Cortical
      thickness and striatal volumes were also compared across groups for the regions
      of interest. RESULTS: Corticostriatal functional correlations were decreased in
      PRD patients relative to elderly control subjects in bilateral prefrontal
      regions; largest difference was observed in the right caudal middle frontal
      region (r = 0.48 in PRD patients and 0.81 in elderly control subjects,
      uncorrected P = .001). Conversely, there was no significant difference across
      groups in the strength of default-network correlations. There was also no
      significant difference across groups in cortical thickness or striatal volume.
      CONCLUSION: PRD was associated with selective disruption of corticostriatal
      resting functional MR imaging correlations, which suggests that resting
      functional MR imaging analyzed in subject-native space may be a useful biomarker
      in this disease. Additionally, at least in the present cohort, this technique was
      more sensitive to PRD changes than was quantitative structural MR imaging.

PMID- 22371612
TI  - Multistability in perception: binding sensory modalities, an overview.
AB  - This special issue presents research concerning multistable perception in
      different sensory modalities. Multistability occurs when a single physical
      stimulus produces alternations between different subjective percepts.
      Multistability was first described for vision, where it occurs, for example, when
      different stimuli are presented to the two eyes or for certain ambiguous figures.
      It has since been described for other sensory modalities, including audition,
      touch and olfaction. The key features of multistability are: (i) stimuli have
      more than one plausible perceptual organization; (ii) these organizations are not
      compatible with each other. We argue here that most if not all cases of
      multistability are based on competition in selecting and binding stimulus
      information. Binding refers to the process whereby the different attributes of
      objects in the environment, as represented in the sensory array, are bound
      together within our perceptual systems, to provide a coherent interpretation of
      the world around us. We argue that multistability can be used as a method for
      studying binding processes within and across sensory modalities. We emphasize
      this theme while presenting an outline of the papers in this issue. We end with
      some thoughts about open directions and avenues for further research.

PMID- 22371613
TI  - Multistability and metastability: understanding dynamic coordination in the
      brain.
AB  - Multistable coordination dynamics exists at many levels, from multifunctional
      neural circuits in vertebrates and invertebrates to large-scale neural circuitry
      in humans. Moreover, multistability spans (at least) the domains of action and
      perception, and has been found to place constraints upon, even dictating the
      nature of, intentional change and the skill-learning process. This paper reviews
      some of the key evidence for multistability in the aforementioned areas, and
      illustrates how it has been measured, modelled and theoretically understood. It
      then suggests how multistability--when combined with essential aspects of
      coordination dynamics such as instability, transitions and (especially)
      metastability--provides a platform for understanding coupling and the creative
      dynamics of complex goal-directed systems, including the brain and the brain
      behaviour relation.

PMID- 22371614
TI  - Properties of auditory stream formation.
AB  - A sequence of sounds may be heard as coming from a single source (called fusion
      or coherence) or from two or more sources (called fission or stream segregation).
      Each perceived source is called a 'stream'. When the differences between
      successive sounds are very large, fission nearly always occurs, whereas when the
      differences are very small, fusion nearly always occurs. When the differences are
      intermediate in size, the percept often 'flips' between one stream and multiple
      streams, a property called 'bistability'. The flips do not generally occur
      regularly in time. The tendency to hear two streams builds up over time, but can
      be partially or completely reset by a sudden change in the properties of the
      sequence or by switches in attention. Stream formation depends partly on the
      extent to which successive sounds excite different 'channels' in the peripheral
      auditory system. However, other factors can play a strong role; multiple streams
      may be heard when successive sounds are presented to the same ear and have
      essentially identical excitation patterns in the cochlea. Differences between
      successive sounds in temporal envelope, fundamental frequency, phase spectrum and
      lateralization can all induce a percept of multiple streams. Regularities in the
      temporal pattern of elements within a stream can help in stabilizing that stream.

PMID- 22371615
TI  - United we sense, divided we fail: context-driven perception of ambiguous visual
      stimuli.
AB  - Ambiguous visual stimuli provide the brain with sensory information that contains
      conflicting evidence for multiple mutually exclusive interpretations. Two
      distinct aspects of the phenomenological experience associated with viewing
      ambiguous visual stimuli are the apparent stability of perception whenever one
      perceptual interpretation is dominant, and the instability of perception that
      causes perceptual dominance to alternate between perceptual interpretations upon
      extended viewing. This review summarizes several ways in which contextual
      information can help the brain resolve visual ambiguities and construct
      temporarily stable perceptual experiences. Temporal context through prior
      stimulation or internal brain states brought about by feedback from higher
      cortical processing levels may alter the response characteristics of specific
      neurons involved in rivalry resolution. Furthermore, spatial or crossmodal
      context may strengthen the neuronal representation of one of the possible
      perceptual interpretations and consequently bias the rivalry process towards it.
      We suggest that contextual influences on perceptual choices with ambiguous visual
      stimuli can be highly informative about the neuronal mechanisms of context-driven
      inference in the general processes of perceptual decision-making.

PMID- 22371616
TI  - The initial phase of auditory and visual scene analysis.
AB  - Auditory streaming and visual plaids have been used extensively to study
      perceptual organization in each modality. Both stimuli can produce bistable
      alternations between grouped (one object) and split (two objects)
      interpretations. They also share two peculiar features: (i) at the onset of
      stimulus presentation, organization starts with a systematic bias towards the
      grouped interpretation; (ii) this first percept has 'inertia'; it lasts longer
      than the subsequent ones. As a result, the probability of forming different
      objects builds up over time, a landmark of both behavioural and
      neurophysiological data on auditory streaming. Here we show that first percept
      bias and inertia are independent. In plaid perception, inertia is due to a depth
      ordering ambiguity in the transparent (split) interpretation that makes plaid
      perception tristable rather than bistable: experimental manipulations removing
      the depth ambiguity suppressed inertia. However, the first percept bias
      persisted. We attempted a similar manipulation for auditory streaming by
      introducing level differences between streams, to bias which stream would appear
      in the perceptual foreground. Here both inertia and first percept bias persisted.
      We thus argue that the critical common feature of the onset of perceptual
      organization is the grouping bias, which may be related to the transition from
      temporally/spatially local to temporally/spatially global computation.

PMID- 22371617
TI  - Multistability, cross-modal binding and the additivity of conjoined grouping
      principles.
AB  - We present a sceptical view of multimodal multistability--drawing most of our
      examples from the relation between audition and vision. We begin by summarizing
      some of the principal ways in which audio-visual binding takes place. We review
      the evidence that unambiguous stimulation in one modality may affect the
      perception of a multistable stimulus in another modality. Cross-modal influences
      of one multistable stimulus on the multistability of another are different: they
      have occurred only in speech perception. We then argue that the strongest
      relation between perceptual organization in vision and perceptual organization in
      audition is likely to be by way of analogous Gestalt laws. We conclude with some
      general observations about multimodality.

PMID- 22371618
TI  - Perceptuo-motor interactions in the perceptual organization of speech: evidence
      from the verbal transformation effect.
AB  - The verbal transformation effect (VTE) refers to perceptual switches while
      listening to a speech sound repeated rapidly and continuously. It is a specific
      case of perceptual multistability providing a rich paradigm for studying the
      processes underlying the perceptual organization of speech. While the VTE has
      been mainly considered as a purely auditory effect, this paper presents a review
      of recent behavioural and neuroimaging studies investigating the role of
      perceptuo-motor interactions in the effect. Behavioural data show that
      articulatory constraints and visual information from the speaker's articulatory
      gestures can influence verbal transformations. In line with these data,
      functional magnetic resonance imaging and intracranial electroencephalography
      studies demonstrate that articulatory-based representations play a key role in
      the emergence and the stabilization of speech percepts during a verbal
      transformation task. Overall, these results suggest that perceptuo (multisensory)
      motor processes are involved in the perceptual organization of speech and the
      formation of speech perceptual objects.

PMID- 22371619
TI  - Functional brain networks underlying perceptual switching: auditory streaming and
      verbal transformations.
AB  - Recent studies have shown that auditory scene analysis involves distributed
      neural sites below, in, and beyond the auditory cortex (AC). However, it remains
      unclear what role each site plays and how they interact in the formation and
      selection of auditory percepts. We addressed this issue through perceptual
      multistability phenomena, namely, spontaneous perceptual switching in auditory
      streaming (AS) for a sequence of repeated triplet tones, and perceptual changes
      for a repeated word, known as verbal transformations (VTs). An event-related fMRI
      analysis revealed brain activity timelocked to perceptual switching in the
      cerebellum for AS, in frontal areas for VT, and the AC and thalamus for both. The
      results suggest that motor-based prediction, produced by neural networks outside
      the auditory system, plays essential roles in the segmentation of acoustic
      sequences both in AS and VT. The frequency of perceptual switching was determined
      by a balance between the activation of two sites, which are proposed to be
      involved in exploring novel perceptual organization and stabilizing current
      perceptual organization. The effect of the gene polymorphism of catechol-O
      methyltransferase (COMT) on individual variations in switching frequency suggests
      that the balance of exploration and stabilization is modulated by catecholamines
      such as dopamine and noradrenalin. These mechanisms would support the noteworthy
      flexibility of auditory scene analysis.

PMID- 22371621
TI  - Multistability in auditory stream segregation: a predictive coding view.
AB  - Auditory stream segregation involves linking temporally separate acoustic events
      into one or more coherent sequences. For any non-trivial sequence of sounds, many
      alternative descriptions can be formed, only one or very few of which emerge in
      awareness at any time. Evidence from studies showing bi-/multistability in
      auditory streaming suggest that some, perhaps many of the alternative
      descriptions are represented in the brain in parallel and that they continuously
      vie for conscious perception. Here, based on a predictive coding view, we
      consider the nature of these sound representations and how they compete with each
      other. Predictive processing helps to maintain perceptual stability by signalling
      the continuation of previously established patterns as well as the emergence of
      new sound sources. It also provides a measure of how well each of the competing
      representations describes the current acoustic scene. This account of auditory
      stream segregation has been tested on perceptual data obtained in the auditory
      streaming paradigm.

PMID- 22371622
TI  - CT fluoroscopy-guided percutaneous gastrostomy with loop gastropexy and peel-away
      sheath trocar technique in 31 amyotrophic lateral sclerosis patients.
AB  - BACKGROUND: In amyotrophic lateral sclerosis (ALS) patients with respiratory
      impairment and/or advanced disease, performing even mild sedation - as is usually
      necessary for percutaneous endoscopic gastrostomy (PEG) placements - is fraught
      with risk. These patients are often referred to Interventional Radiology for
      alternative percutaneous gastrostomy tube placement options. PURPOSE: To report
      our experience with CT fluoroscopy-guided percutaneous gastrostomy with a novel
      loop gastropexy and peel-away sheath trocar technique in ALS patients as an
      alternative to endoscopic techniques. MATERIAL AND METHODS: A consecutive series
      of 31 amyotrophic lateral sclerosis patients in whom endoscopic gastrostomy was
      considered too dangerous or impossible to perform underwent CT-guided
      percutaneous gastropexy and gastrostomy and prospective follow-up. All procedures
      were performed with a 15 FR Freka(r) Pexact gastrostomy kit, a 16-row CT scanner
      (Aquilion 16) and single shot CT fluoroscopy mode. RESULTS: The procedure was
      performed successfully in 30 of 31 patients (20 men, 11 women; median age 60
      years, range 38-80 years). In the remaining case the stomach was punctured under
      CT fluoroscopy and CO2 insufflation was initiated thereafter, leading to
      successful gastrostomy without prior gastropexy and without further adverse
      events during follow-up. Two patients reported unproblematic exchange of a
      balloon tube due to skin irritations with no further adverse events. One patient
      reported accidental displacement of an exchanged new balloon tube in domestic
      environment due to balloon leakage: A new balloon tube was easily re-inserted in
      a hospital the same day. No serious adverse events such as peritonitis,
      persistent local bleeding, systemic blood loss, or any local infection requiring
      surgical intervention were observed. Until August 11, 2011 follow-up resulted in
      7473 cumulative gastrostomy-days from the date of first placement. CONCLUSION:
      Initial results suggest that the described technique under CT guidance is
      feasible and safe and may especially be advantageous in cases where endoscopic
      gastrostomy and sedation are contraindicated.

PMID- 22371620
TI  - Variability of perceptual multistability: from brain state to individual trait.
AB  - Few phenomena are as suitable as perceptual multistability to demonstrate that
      the brain constructively interprets sensory input. Several studies have outlined
      the neural circuitry involved in generating perceptual inference but only more
      recently has the individual variability of this inferential process been
      appreciated. Studies of the interaction of evoked and ongoing neural activity
      show that inference itself is not merely a stimulus-triggered process but is
      related to the context of the current brain state into which the processing of
      external stimulation is embedded. As brain states fluctuate, so does perception
      of a given sensory input. In multistability, perceptual fluctuation rates are
      consistent for a given individual but vary considerably between individuals.
      There has been some evidence for a genetic basis for these individual differences
      and recent morphometric studies of parietal lobe regions have identified
      neuroanatomical substrates for individual variability in spontaneous switching
      behaviour. Moreover, disrupting the function of these latter regions by
      transcranial magnetic stimulation yields systematic interference effects on
      switching behaviour, further arguing for a causal role of these regions in
      perceptual inference. Together, these studies have advanced our understanding of
      the biological mechanisms by which the brain constructs the contents of
      consciousness from sensory input.

PMID- 22371623
TI  - MR angiography in tuberculous meningitis.
AB  - BACKGROUND: Infarctions in tuberculous meningitis (TBM) are common but there is a
      paucity of studies on MR angiography (MRA). PURPOSE: To evaluate the pattern and
      predictors of MRA abnormality in patients with TBM. MATERIAL AND METHODS: Sixty
      seven patients with TBM were subjected to clinical, laboratory, magnetic
      resonance imaging (MRI), and MRA evaluation. The severity of meningitis, focal
      deficit, CSF findings, and stroke co-morbidities were recorded. Presence of
      exudates, infarction, hydrocephalous, and tuberculoma on MRI were noted. On
      intracranial MRA, occlusion or more than 50% narrowing of proximal middle
      cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral
      artery (PCA), and basilar artery were considered abnormal. The MRA abnormality
      was correlated with clinical, laboratory, and MRI findings. RESULTS: Sixty-seven
      patients, aged 3-75 years (median 34 years) were included. MRI was abnormal in 61
      (91%) patients; basal exudates in 24, hydrocephalous in 23, tuberculoma in 33,
      and infarction in 40. MRA was abnormal in 34 (50.7%); MCA was most commonly
      involved (n = 21), followed by PCA (n = 14), ICA (n = 8), ACA (n = 5), basilar
      artery (n = 5), and vertebral and superior cerebellar artery (1 each). One-fourth
      of the patients had abnormality in both anterior and posterior circulations. MRA
      abnormality was related to hydrocephalous and infarction; corresponding infarct
      was present in 61.8% patients; 41.7% patients with abnormal MRA developed infarct
      at 3 months but none with normal MRA. CONCLUSION: Half the patients with TBM had
      MRA abnormality involving both anterior and posterior circulations and 61.8% of
      them had corresponding infarcts.

PMID- 22371624
TI  - Overtime reliability of medial temporal lobe atrophy rating in a clinical
      setting.
AB  - BACKGROUND: Medial temporal lobe atrophy (MTA) is one of the first magnetic
      resonance imaging (MRI) signs in patients with Alzheimer's disease (AD) and used
      as a measure of disease progression. Visual assessment of MTA is easy to perform
      but the reliability of MTA rating over time has not been studied. PURPOSE: To
      investigate what happens to the MTA rating scores if two radiologists rate the
      same MRI scans six times over a period of 1 year. MATERIAL AND METHODS: One
      hundred outpatients were included in this study. All patients underwent MRI with
      a protocol and sequences used for geriatric patients, according to local clinical
      standards. One neuroradiologist and one general radiologist independently of each
      other performed retrospective visual assessments of MTA six times, using the same
      scans, over a period of 1 year. RESULTS: Intra-rater kappa varied between kappa
      0.65 and 0.84 for the neuroradiologist and kappa 0.38 and 0.74 for the general
      radiologist. Intra-rater weighted kappa (wkappa) values showed almost perfect
      agreement for both investigators (wkappa 0.83-0.94). Inter-rater reliability
      showed fair to moderate agreement, with the kappa value varying from kappa 0.29
      to 0.48 and weighted kappa values ranging from wkappa 0.72 to 0.84. There was a
      statistically significant difference in rating between the two investigators.
      CONCLUSION: Visual assessment of MTA repeated over time has a high grade of
      reproducibility when performed by an experienced investigator. The
      reproducibility drops when assessment is rarely performed. Inter-rater
      reliability is low when two investigators not working together are compared.

PMID- 22371625
TI  - The role of elevated growth hormone on the increased atherosclerosis in patients
      with acromegaly.

PMID- 22371626
TI  - Reduced plasma eicosapentaenoic acid-arachidonic acid ratio in peripheral artery
      disease.
AB  - A reduced ratio of plasma eicosapentaenoic acid-arachidonic acid (EPA-AA) is a
      newly recognized atherosclerotic risk factor. This ratio has not been fully
      investigated in peripheral artery disease (PAD). Seventy Japanese patients with
      atherosclerotic risk factors were enrolled and divided into 2 groups, those with
      PAD (group A: n = 38) and those without PAD (group B: n = 32). The EPA-AA ratio
      (P = .001) and ankle-brachial index (ABI: P < .001) in group A were significantly
      lower than those in group B. Univariate and multivariate analyses demonstrated
      that EPA-AA, ABI, and prescription of clopidogrel had significant correlation
      with PAD. Given the appropriate cutoff values, EPA-AA (odds ratio [OR] = 11.7,
      95% confidence interval [CI] = 3.0-45.8; P < .001) and ABI (OR = 44.0, 95% CI =
      5.4-358.5; P < .001) are factors independently associated with PAD. In
      conclusion, this study demonstrated that reduced plasma EPA/AA may underlie PAD
      at least in Japanese.

PMID- 22371627
TI  - Prevalence of intron 1 inversion of cases with hemophilia A in North Indian
      population.
AB  - Hemophilia A is an X-linked bleeding disorder resulting from heterogeneous
      mutations in the factor VIII (FVIII) gene. The disease is frequently caused by
      intron 22 inversion mutation in FVIII gene in approximately 50% cases and by
      intron 1 inversion (Inv1) in 2% to 5% cases with severe hemophilia A. Both
      inversion mutations occur due to intrachromosomal recombination between inverted
      repeats found in intronic sequences in upstream regions located telomeric to the
      FVIII gene and result in a severe phenotype. Frequency of Inv1 mutation varies in
      different populations. We have analyzed the frequency of the Inv1 in a group of
      110 cases with Hemophilia A from North Indian Population and found 4 inversion
      positive cases (3.6%). The Inv1 genotyping was further applied to analyze the
      hemophilia carrier status of the mother and proband's sister. Direct mutation
      detection strategy is more perfective in diagnosis of cases, carriers, and in
      prenatal diagnosis of hemophilia A.

PMID- 22371628
TI  - Reflections on evidence and the place of reflective practice.

PMID- 22371629
TI  - Complementary or controversial care? The opinions of professionals on
      complementary and alternative interventions for Autistic Spectrum Disorder.
AB  - The use of complementary and alternative interventions is growing and gaining
      popularity, both in the UK and internationally, with significant financial and
      emotional implications. Complementary and alternative interventions are often
      utilised by parents of children with Autistic Spectrum Disorders and research has
      investigated parental beliefs. There is, however, limited understanding regarding
      what professionals believe about the use of alternative treatments. In this paper
      we explore the opinions of a range of different professionals about alternative
      treatments and found that while some have an open-minded opinion, there was a
      tendency to hold beliefs that these treatments are ineffective, that they give
      false hope and have potential to harm the child. We discuss the implications for
      this in terms of the importance of an open dialogue between professionals and
      families and consider the importance of this in relation to the popularity of
      these interventions.

PMID- 22371630
TI  - National Institute of Neurological Disorders and Stroke Common Data Element
      Project - approach and methods.
AB  - BACKGROUND: In neuroscience clinical research studies, much time and effort are
      devoted to deciding what data to collect and developing data collection forms and
      data management systems to capture the data. Many investigators receiving funding
      from National Institute of Neurological Disorders and Stroke (NINDS), the
      National Institutes of Health (NIH), are required to share their data once their
      studies are complete, but the multitude of data definitions and formats make it
      extremely difficult to aggregate data or perform meta-analyses across studies.
      PURPOSE: In an effort to assist investigators and accelerate data sharing in
      neuroscience clinical research, the NINDS has embarked upon the Common Data
      Element (CDE) Project. The data standards developed through the NINDS CDE Project
      enable clinical investigators to systematically collect data and should
      facilitate study start-up and data aggregation across the research community.
      METHODS: The NINDS CDE Team has taken a systematic, iterative approach to develop
      the critical core and the disease-specific CDEs. The CDE development process
      provides a mechanism for community involvement and buy-in, offers a structure for
      decision making, and includes a technical support team. RESULTS: Upon conclusion
      of the development process, the CDEs and accompanying tools are available on the
      Project Web site - http://www.commondataelements.ninds.nih.gov/. The Web site
      currently includes the critical core (aka general) CDEs that are applicable to
      all clinical research studies regardless of therapeutic area as well as several
      disease-specific CDEs. Additional disease-specific CDEs will be added to the Web
      site once they are developed and vetted over the next 12 months. LIMITATIONS: The
      CDEs will continue to evolve and will improve only if clinical researchers use
      and offer feedback about their experience with them. Thus, the NINDS program
      staff strongly encourages its clinical research grantees to use the CDEs and is
      expanding its efforts to educate the neuroscience research community about the
      CDEs and to train research teams to incorporate them into their studies.
      CONCLUSIONS: Version 1.0 of a set of CDEs has been published, but publication is
      not the end of the development process. All CDEs will be evaluated and revised at
      least annually to ensure that they reflect current clinical research practices in
      neuroscience.

PMID- 22371631
TI  - Predicting symptoms of post-traumatic stress among patients undergoing orthopedic
      surgery on the basis of routinely collected cardiovascular data.
AB  - The present study examined whether in-hospital assessments of heart rate and
      blood pressure predicted symptoms of post-traumatic stress (PTS) in 110 patients
      undergoing total knee replacement surgery. After controlling for conceptually
      relevant factors, in-hospital cardiovascular functioning predicted symptoms of
      PTS three months following surgery. Specifically, lower pre-surgical and post
      surgical systolic and diastolic blood pressure predicted more symptoms of
      avoidance and PTS (total). In contrast, higher heart rate prior to and shortly
      following surgery predicted marginally more intrusive thoughts. The present
      findings suggest that routinely collected medical data may provide a means to
      identify patients at risk for problematic outcomes following surgery.

PMID- 22371632
TI  - Role of cytokines and chemokines in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological
      conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and
      hepatocarcinoma) that are characterized by an increased fat content within the
      liver. The accumulation/deposition of fat within the liver is essential for
      diagnosis of NAFLD and might be associated with alterations in the hepatic and
      systemic inflammatory state. Although it is still unclear if each histological
      entity represents a different disease or rather steps of the same disease,
      inflammatory processes in NAFLD might influence its pathophysiology and
      prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed
      condition in NAFLDs, which more frequently evolves towards chronic and serious
      liver diseases) is characterized by a marked activation of inflammatory cells and
      the upregulation of several soluble inflammatory mediators. Among several
      mediators, cytokines and chemokines might play a pivotal active role in NAFLD and
      are considered as potential therapeutic targets. In this review, we will update
      evidence from both basic research and clinical studies on the potential role of
      cytokines and chemokines in the pathophysiology of NAFLD.

PMID- 22371634
TI  - Routine blood tests to predict liver fibrosis in chronic hepatitis C.
AB  - AIM: To verify the usefulness of FibroQ for predicting fibrosis in patients with
      chronic hepatitis C, compared with other noninvasive tests. METHODS: This
      retrospective cohort study included 237 consecutive patients with chronic
      hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ,
      aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to
      platelet ratio index, cirrhosis discriminant score, age-platelet index (API),
      Pohl score, FIB-4 index, and Lok's model were calculated and compared. RESULTS:
      FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as
      fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be
      superior in predicting significant fibrosis score in chronic hepatitis C compared
      with other noninvasive tests. CONCLUSION: FibroQ is a simple and useful test for
      predicting significant fibrosis in patients with chronic hepatitis C.

PMID- 22371633
TI  - Developments in metastatic pancreatic cancer: is gemcitabine still the standard?
AB  - In the past 15 years, we have seen few therapeutic advances for patients with
      pancreatic cancer, which is the fourth leading cause of cancer-related death in
      the United States. Currently, only about 6% of patients with advanced disease
      respond to standard gemcitabine therapy, and median survival is only about 6 mo.
      Moreover, phase III trials have shown that adding various cytotoxic and targeted
      chemotherapeutic agents to gemcitabine has failed to improve overall survival,
      except in cases in which gemcitabine combined with erlotinib show minimal
      survival benefit. Several meta-analyses have shown that the combination of
      gemcitabine with either a platinum analog or capecitabine may lead to clinically
      relevant survival prolongation, especially for patients with good performance
      status. Meanwhile, many studies have focused on the pharmacokinetic modulation of
      gemcitabine by fixed-dose administration, and metabolic or transport enzymes
      related to the response and toxicity of gemcitabine. Strikingly, a phase III
      trial in 2010 showed that, in comparison to gemcitabine alone, the FOLFIRINOX
      regimen in patients with advanced disease and good performance status, produced
      better median overall survival, median progression-free survival, and objective
      response rates. This regimen also resulted in greater, albeit manageable
      toxicity.

PMID- 22371635
TI  - Effects of resistin-like molecule beta over-expression on gastric cancer cells in
      vitro.
AB  - AIM: To investigate the effects of resistin-like molecule beta (RELMbeta) over
      expression on the invasion, metastasis and angiogenesis of gastric cancer cells.
      METHODS: Human RELMbeta encoding expression vector was constructed and
      transfected into the RELMbeta lowly-expressed gastric cancer cell lines SGC-7901
      and MKN-45. Gene expression was measured by Western blotting, reverse
      transcription polymerase chain reaction (PCR) and real-time quantitative PCR.
      Cell proliferation was measured by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl
      tetrazolium bromide colorimetry, colony formation and 5-ethynyl-20-deoxyuridine
      incorporation assays. The in vitro migration, invasion and metastasis of cancer
      cells were measured by cell adhesion assay, scratch assay and matrigel invasion
      assay. The angiogenic capabilities of cancer cells were measured by tube
      formation of endothelial cells. RESULTS: Transfection of RELMbeta vector into SGC
      7901 and MKN-45 cells resulted in over-expression of RELMbeta, which did not
      influence the cellular proliferation. However, over-expression of RELMbeta
      suppressed the in vitro adhesion, invasion and metastasis of cancer cells,
      accompanied by decreased expression of matrix metalloproteinase-2 (MMP-2) and MMP
      9. Moreover, transfection of RELMbeta attenuated the expression of vascular
      endothelial growth factor and in vitro angiogenic capabilities of cancer cells.
      CONCLUSION: Over-expression of RELMbeta abolishes the invasion, metastasis and
      angiogenesis of gastric cancer cells in vitro, suggesting its potentials as a
      novel therapeutic target for gastric cancer.

PMID- 22371636
TI  - Rifaximin vs. conventional oral therapy for hepatic encephalopathy: a meta
      analysis.
AB  - AIM: To characterize the efficacy of rifaximin in the management of hepatic
      encephalopathy (HE) as several randomized controlled studies have shown
      contradictory results on its effectiveness in comparison to other oral agents.
      METHODS: We performed a systematic review and random effects meta-analysis of all
      eligible trials identified through electronic and manual searches. Twelve
      randomized controlled trials met the inclusion criteria with a total of 565
      patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to
      disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08]
      but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion
      of treatment protocols, patients receiving rifaximin showed lower serum ammonia
      levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10],
      better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less
      asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical
      significance. On the other hand, other psychometric outcomes such as
      electroencephalographic response and grades of portosystemic encephalopathy were
      superior in patients treated with rifaximin in comparison to the control group
      (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98,
      P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any
      significant difference in the above findings. CONCLUSION: Rifaximin appears to be
      at least as effective as other conventional oral agents for the treatment of HE
      with a better safety profile.

PMID- 22371637
TI  - Immunoexpression of cyclooxygenase-2 in primary gastric carcinomas and lymph node
      metastases.
AB  - AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric
      carcinomas and respective lymph node metastases. METHODS: Immunohistochemistry to
      analyze COX-2 expression was performed on tissue microarray slices obtained from
      36 specimens of gastrectomy and satellite lymph nodes from patients with gastric
      carcinoma. RESULTS: Immunostaining was seen in most cases, and COX-2 expression
      was higher in lymph node metastases than in corresponding primary gastric tumors
      of intestinal, diffuse and mixed carcinomas, with a statistically significant
      difference in the diffuse histotype (P = 0.0108). CONCLUSION: COX-2
      immunoexpression occurs frequently in primary gastric carcinomas, but higher
      expression of this enzyme is observed in lymph node metastases of the diffuse
      histotype.

PMID- 22371638
TI  - Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces
      specific immune responses in mice.
AB  - AIM: To explore dendritic cells (DCs) multiple functions in immune modulation.
      METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with
      pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice.
      Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived
      envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a
      single epitope, but the whole "viral surface" induces immunogenicity. For
      vaccination, mature and activated DC were injected subcutaneously twice. RESULTS:
      Humoral and cellular immune responses measured by enzyme-linked immunosorbent
      assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody
      production as well as T-cells directed against HCV. Furthermore, T-cell responses
      confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable
      region 1. CONCLUSION: Our results indicate dendritic cells as a promising
      vaccination model for HCV infection that should be evaluated further.

PMID- 22371639
TI  - Effects of endoscopic sphincterotomy on biliary epithelium: a case-control study.
AB  - AIM: To study the long-term effects of endoscopic sphincterotomy on biliary
      epithelium. METHODS: This is a prospective case-control study. A total of 25
      patients with a median age of 71 years (range 49-89 years) and prior endoscopic
      sphincterotomy (ES) for benign disease formed the first group. The median time
      from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76
      years (range 44-94 mo) and similar characteristics who underwent current
      endoscopic retrograde cholangiopancreatography (ERCP) and ES for benign disease
      formed the second group (control group). Brush cytology of the biliary tree with
      p53 immunocytology was performed in all patients of both groups. ERCPs and
      recruitment were conducted at the Endoscopic Unit of Aretaieion University
      Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS:
      No cases were positive or suspicious for malignancy. Epithelial atypia was higher
      in the first group (32% vs. 8% in the second group, P = 0.034). Acute cholangitis
      and previous biliary operation rates were also higher in the first group (acute
      cholangitis, 60% vs. 24% in the second group, P = 0.01; previous biliary
      operation, 76% vs. 24% in the second group, P = 0.001). Subgroup analysis showed
      that previous ES was the main causal factor for atypia, which was not related to
      the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the
      first group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia
      that represents mostly reactive/proliferative rather than premalignant changes.
      The role of p53 immunoreactivity in biliary atypia needs to be further studied.

PMID- 22371640
TI  - Vitamin D improves viral response in hepatitis C genotype 2-3 naive patients.
AB  - AIM: To examine whether vitamin D improved viral response and predicted treatment
      outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty
      patients with chronic HCV genotype 2-3 were randomized consecutively into two
      groups: Treatment group [20 subjects, age 48 +/- 14 years, body mass index (BMI)
      30 +/- 6, 65% male], who received 180 MUg pegylated alpha-interferon-2a plus oral
      ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops;
      2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control
      group (30 subjects, age 45 +/- 10 years, BMI 26 +/- 3, 60% male), who received
      identical therapy without vitamin D. HCV RNA was assessed by reverse
      transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk
      after treatment was considered as rapid virological response, complete early
      virological response, and sustained virological response (SVR), respectively.
      Biomarkers of inflammation were measured. RESULTS: The treatment group with
      vitamin D had higher BMI (30 +/- 6 vs. 26 +/- 3, P < 0.02), and high viral load
      (> 400,000 IU/mL, 65% vs. 40%, P < 0.01) than controls. Ninety-five percent of
      treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment
      (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA
      negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20
      +/- 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of
      (34 +/- 11 ng/mL). Logistic regression analysis identified vitamin D supplement
      [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or
      > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as
      independent predictors of viral response. Adverse events were mild and typical of
      Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome,
      and adding vitamin D to conventional Peg/RBV therapy for patients with HCV
      genotype 2-3 significantly improves viral response.

PMID- 22371641
TI  - Simultaneous laparoscopic multi-organ resection combined with colorectal cancer:
      comparison with non-combined surgery.
AB  - AIM: To access the short-term outcomes of simultaneous laparoscopic surgery
      combined with resection for synchronous lesions in patients with colorectal
      cancer. METHODS: Between March 1996 and April 2010 prospectively collected data
      were reviewed from 93 consecutive patients who had colorectal cancer and
      underwent simultaneous multiple organ resection (combined group) and 1090
      patients who underwent conventional laparoscopic right hemicolectomy or
      laparoscopic low/anterior resection for colorectal cancer (non-combined group).
      In the combined group, there were nine gastric resections, three nephrectomies,
      nine adrenalectomies, 56 cholecystectomies, and 21 gynecologic resections. In
      addition, five patients underwent simultaneous laparoscopic resection for three
      organs. The patient demographics, intra-operative outcomes, surgical morbidity,
      and short-term outcomes were compared between the two groups (the combined and
      non-combined groups). RESULTS: There were no significant differences in the
      clinicopathological variables between the two groups. The operating time was
      significantly longer in the combined group than in the non-combined group,
      regardless of tumor location (laparoscopic right hemicolectomy and laparoscopic
      low/anterior resection groups; P = 0.048 and P < 0.001, respectively). The other
      intra-operative outcomes, such as the complications and open conversion rate,
      were similar in both groups. The rate of post-operative morbidity in the combined
      group was similar to the non-combined group (combined vs non-combined, 15.1% vs
      13.5%, P = 0.667). Oncological safety for the colon and synchronous lesions were
      obtained in the combined group. CONCLUSION: Simultaneous laparoscopic multiple
      organ resection combined with colorectal cancer is a safe and feasible option in
      selected patients.

PMID- 22371642
TI  - Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients.
AB  - AIM: To investigate the protein expression profile of mismatch repair (MMR) genes
      in suspected cases of Lynch syndrome and to characterize the associated germline
      mutations. METHODS: Immunohistochemical analysis of tumor samples was performed
      to determine the protein expression profile of MMR protein. Germline mutation
      screening was carried out on peripheral blood samples. The entire exon regions of
      MLH1 and MSH2 genes were amplified by polymerase chain reaction, screened by
      denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA
      sequencing to characterize the germline mutations. RESULTS: Three out of 34
      tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of
      nuclear staining by immunohistochemistry, indicating the absence of MLH1 and MSH2
      protein expression in carcinoma cells, respectively. dHPLC analysis followed by
      DNA sequencing showed these samples to have germline mutations of MSH2 gene.
      However, no deleterious mutations were identified in any of the 19 exons or
      coding regions of MLH1 gene, but we were able to identify MLH1 promoter
      polymorphism, -93G > A (rs1800734), in 21 out of 34 patients (61.8%). We
      identified one novel mutation, transversion mutation c.2005G > C, which resulted
      in a missense mutation (Gly669Arg), a transversion mutation in exon 1, c.142G >
      T, which resulted in a nonsense mutation (Glu48Stop) and splice-site mutation,
      c.2006-6T > C, which was adjacent to exon 13 of MSH2 gene. CONCLUSION: Germline
      mutations were identified in four Malaysian Lynch syndrome patients.
      Immunohistochemical analysis of tumor tissue proved to be a good pre-screening
      test before proceeding to germline mutation analysis of DNA MMR genes.

PMID- 22371643
TI  - Meta-analysis of combined therapy for adult hepatitis B virus-associated
      glomerulonephritis.
AB  - AIM: To investigate the efficacy and safety of combined antiviral and
      immunosuppressant therapy in adult hepatitis B virus-associated
      glomerulonephritis (HBV-GN) patients. METHODS: A computerized literature search
      was carried out in the PubMed database, Embase, the Cochrane Library, Chinese
      BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National
      Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of
      Database) to collect articles between June 1980 and December 2010 on therapy with
      immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and
      leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir
      and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were
      remission of proteinuria, clearance of HBV e-antigen, and elevation of serum
      albumin. The secondary outcomes were blood levels of alanine aminotransferase,
      serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review
      Manager 5.1. Fixed or random effect models were employed to combine the results
      after a heterogeneity test. The effects of the combined therapy were analyzed for
      different doses of glucorticosteroid and different types of HBV-GN. RESULTS:
      Twelve clinical trials with 317 patients were included. A significantly higher
      incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI:
      1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean
      difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin
      concentration significantly with a mean difference of -11.95 (95% CI: -12.97
      10.93) without significant alterations of liver function (mean difference: 4.62,
      95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14
      20.45). No significant activation of HBV-DNA replication occurred (mean
      difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference
      between the high dose glucorticosteroid group and the low dose glucorticosteroid
      group in terms of proteinuria remission (P = 0.76) and between different
      pathological types of HBV-GN [membranous glomerulonephritis (MN) vs. mesangial
      proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative
      glomerulonephritis, P = 0.27]. CONCLUSION: Combined antiviral and
      immunosuppressant therapy can improve the proteinuria in HBV-GN patients without
      altering HBV replication or damaging liver and renal functions.

PMID- 22371644
TI  - D2 dissection in laparoscopic and open gastrectomy for gastric cancer.
AB  - AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for
      gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric
      cancer, who underwent radical gastrectomy with D2 dissection between January 2007
      and February 2011, were analyzed retrospectively. Among these patients, 131
      patients underwent laparoscopy-assisted gastrectomy (LAG) and 78 underwent open
      gastrectomy (OG). The parameters analyzed included operative time, blood loss,
      blood transfusion, morbidity, mortality, the number of harvested lymph nodes
      (HLNs), and pathological stage. RESULTS: There were no significant differences in
      sex, age, types of radical resection [radical proximal gastrectomy (PG + D2),
      radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)],
      and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127
      cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average
      number of HLNs was 26.1 +/- 11.4 in the LAG group and 24.2 +/- 9.3 in the OG
      group (P = 0.233). In the same type of radical resection, there were no
      significant differences in the number of HLNs between the two groups (PG + D2:
      21.7 +/- 7.5 vs. 22.4 +/- 9.3; DG + D2: 25.7 +/- 11.0 vs. 22.3 +/- 7.9; TG + D2:
      30.9 +/- 13.4 vs. 29.3 +/- 10.4; P > 0.05 for all comparisons). Tumor free
      margins were obtained in all cases. Compared with OG group, the LAG group had
      significantly less blood loss, but a longer operation time (P < 0.001). The
      morbidity of the LAG group was 9.9%, which was not significantly different from
      the OG group (7.7%) (P = 0.587). The mortality was zero in both groups.
      CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs,
      regardless of tumor location. Thus, this procedure can achieve the same
      radicalness as OG.

PMID- 22371645
TI  - Expression of fibroblast activation protein in human pancreatic adenocarcinoma
      and its clinicopathological significance.
AB  - AIM: To examine fibroblast activation protein (FAP) expression in pancreatic
      ductal adenocarcinoma (PDAC) and to analyze its relationship with the
      clinicopathology of PDAC. METHODS: FAP expression was examined in 134 PDAC
      specimens by immunohistochemistry, and in four pancreatic cancer cell lines
      (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also
      analyzed the association between FAP expression in PDAC cells and the
      clinicopathology of PDAC patients. RESULTS: The results showed that the FAP was
      ex-pressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells
      (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at
      different levels. Protein bands corresponding to the proteolytically active 170
      kDa seprase dimer and its 88-kDa seprase subunit were identified. Higher FAP
      expression in carcinoma cells was associated with tumor size (P < 0.001),
      fibrotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical
      outcome (P = 0.0085). CONCLUSION: FAP is highly expressed in carcinoma cells and
      fibroblasts in PDAC tissues, and its expression is associated with desmoplasia
      and worse prognosis.

PMID- 22371646
TI  - Interleukin-10-1082G/A polymorphism and acute liver graft rejection: a meta
      analysis.
AB  - AIM: To investigate the association between interleukin (IL)-10-1082 (G/A)
      promoter polymorphism and acute rejection (AR) in liver transplant (LT)
      recipients. METHODS: Two investigators independently searched the Medline,
      Embase, China National Knowledge Infrastructure, and Chinese Biomedicine
      Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism
      and AR were calculated in a fixed- and a random-effects model as appropriate.
      RESULTS: This meta-analysis included seven case-control studies, which comprised
      652 cases of LT recipients in which 241 cases developed AR and 411 cases did not
      develop AR. Overall, the variant A allele was not associated with AR risk when
      compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover,
      similar results were observed when the AA genotype was compared with the AG/GG
      genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for ethnicity, no
      significant association was observed among either Caucasians or Asians. Because
      only one study was performed in Asian patients, the result of subgroup analysis
      by ethnicity would not be reliable for Asians. Limiting the analysis to the
      studies with controls in the Hardy-Weinberg equilibrium, the results were
      persistent and robust. No publication bias was found in the present study.
      CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be
      not associated with AR risk in LT recipients among Caucasians.

PMID- 22371647
TI  - Amplifications of NCOA3 gene in colorectal cancers in a Chinese population.
AB  - AIM: To investigate the copy number variation of NACO3 gene in colorectal cancer
      (CRC) and its correlation with tumor progression. METHODS: A total of 142 samples
      of case-matched CRC tissues and adjacent normal tissues were obtained from
      patients undergoing bowel resection. Quantitative real-time polymerase chain
      reaction method was used to investigate the copy number variations of NCOA3 as
      well as gene expression in the collected tissues. RESULTS: Copy number gains of
      NCOA3 were detected in 39 CRC samples (27.5%) and were correlated with tumor
      progression (chi2 = 6.42, P = 0.0112). Moreover, there was a positive correlation
      between copy number gain and mRNA over-expression of NCOA3 in CRCs (P = 0.0023).
      Expression level of NCOA3 mRNA was also enhanced in the CRC samples with
      unaltered copy numbers (3.85 +/- 1.23 vs. 2.71 +/- 0.64, P < 0.01). CONCLUSION:
      Sporadic colorectal cancers exhibit different mechanisms of NCOA3 regulation.

PMID- 22371648
TI  - A case of Cowden syndrome diagnosed from multiple gastric polyposis.
AB  - Cowden syndrome is a rare autosomal dominant disorder that is characterized by
      multiple hamartomas in a variety of tissues and this is associated with germline
      mutations in the phosphatase and tensin homologue (PTEN) gene, which is the tumor
      suppressor gene located on chromosome 10q23.3. It is characterized by multiple
      hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal (GI) tract,
      bones, central nervous system, eyes, and genitourinary tract. Cowden syndrome
      does not have increased risk of GI malignancy; however, it has an increased risk
      of breast, thyroid and endometrial cancer development. Here the authors report a
      rare case of Cowden syndrome incidentally diagnosed from multiple gastric
      polyposis. A 29-year-old woman presented with multiple gastric polyps. The
      laboratory results were normal except for mild anemia, with a hemoglobin level of
      11.9 g/dL. Esophagogastroduodenoscopy revealed multiple gastric, duodenal polyps
      and esophageal acanthosis. Colonoscopy revealed possible hamartomatous polyps in
      the rectum. Under the suspicion of Cowden syndrome, sonography of the thyroid and
      breasts was carried out, which revealed multiple thyroid masses. Subsequent fine
      needle aspiration biopsy revealed the presence of clusters of follicular
      epithelial cells, and due to the possibility of malignancy, the patient underwent
      total thyroidectomy. The pathology was reported as invasive follicular carcinoma.
      A gene study by direct sequencing showed the presence of a PTEN mutation (c.633C
      > A /p.Cys211*).

PMID- 22371649
TI  - Five-year follow-up of a one-year self-management program for patients with COPD.
AB  - OBJECTIVE: Investigate long-term effects 4 years after the end of a 1-year self
      management program (SMP) with 30 hours of education and 16 hours of physical
      activity in patients with chronic obstructive pulmonary disease (COPD). METHODS:
      Prospective observational outcome study. SMP focused on improving disease related
      self-care skills. Main outcome measures were health-related quality of life,
      HRQoL, (St Georges Respiratory Questionnaire, SGRQ total) and exercise capacity
      (6-minute walk test, 6MWT). RESULTS: Thirty patients participated, 47% women.
      Baseline mean age was 67 years and mean pre-bronchodilator FEV(1) (forced
      expiratory volume in 1 second) percentage predicted was 41.3. HRQoL showed a
      statistical significant improvement during the 1-year intervention. Four years
      after the end of the program SGRQ total was similar to baseline value, 1.4 points
      (95% CI: -3.6 to 6.3, P = 0.580). Also 6MWT was similar to baseline value at the
      same test point, -10 m (95% CI: -27 to 8, P = 0.262), and 63% reported having
      continued to exercise regularly a minimum of three times per week during the
      follow-up period. CONCLUSION: The participants in a 1-year self-management
      program with additional training had maintained their pre-intervention level of
      HRQoL and exercise capacity 4 years after the end of the program. Two out of
      three participants had continued to exercise regularly.

PMID- 22371650
TI  - Lung function decline in COPD.
AB  - The landmark study of Fletcher and Peto on the natural history of tobacco smoke
      related chronic airflow obstruction suggested that decline in the forced
      expiratory volume in the first second (FEV(1)) in chronic obstructive pulmonary
      disease (COPD) is slow at the beginning, becoming faster with more advanced
      disease. The present authors reviewed spirometric data of COPD patients included
      in the placebo arms of recent clinical trials to assess the lung function decline
      of each stage, defined according to the severity of airflow obstruction as
      proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      guidelines. In large COPD populations the mean rate of FEV(1) decline in GOLD
      stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year,
      respectively, and lower than 35 mL/year in GOLD stage IV. Few data on FEV(1)
      decline are available for GOLD stage I. Hence, the loss of lung function,
      assessed as expiratory airflow reduction, seems more accelerated and therefore
      more relevant in the initial phases of COPD. To have an impact on the natural
      history of COPD, it is logical to look at the effects of treatment in the earlier
      stages.

PMID- 22371651
TI  - Guideline-based survey of outpatient COPD management by pulmonary specialists in
      Germany.
AB  - BACKGROUND: Little is known about the role of guidelines for the practical
      management of chronic obstructive pulmonary disease (COPD) by office-based
      pulmonary specialists. The aim of this study was to assess their outpatient
      management in relation to current guideline recommendations for COPD. METHODS: A
      nationwide prospective cross-sectional COPD questionnaire survey in the form of a
      multiple-choice questionnaire was sent to 1000 office-based respiratory
      specialists in Germany. The product-neutral questions focused on routine COPD
      management and were based on current national and international COPD guideline
      recommendations being consistent in severity classification and treatment
      recommendations. RESULTS: A total of 590 pulmonary specialists (59%) participated
      in the survey. Body plethysmography was considered the standard for diagnosis
      (65.9%), followed by spirometry (32%). Most respondents were able to cite the
      correct spirometric criteria for classifying moderate (87%) to very severe COPD
      (77%). A quarter of the respondents equated the World Health Organization (WHO)
      definition of chronic bronchitis with COPD. Notably, most participants preferred
      the updated national COPD guidelines (51.4%) to the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guidelines (40.2%). Improvement of functional
      exercise capacity and quality of life were considered the two most relevant
      treatment goals; whereas impact on mortality was secondary. Treatment of COPD
      largely complied with the guidelines. However, a significant percentage of the
      pulmonary specialists differed in their assessment of the benefits of various
      therapeutic measures from evidence-based results. Referral for pulmonary
      rehabilitation was uncommon, regardless of the severity of COPD. CONCLUSION: The
      findings of this large national survey suggest that most pulmonary specialists
      adhere to the current COPD guideline recommendations in daily practice. However,
      physicians' knowledge of guidelines is not sufficient as the sole benchmark when
      assessing their implementation in day-to-day practice. Necessary changes in the
      health care system must include more effective ways to transfer knowledge to
      clinical practice and to give access to interventions of proven clinical benefit.

PMID- 22371652
TI  - Doppler ultrasound venous mapping of the lower limbs.
AB  - BACKGROUND: The study aim was to test the accuracy (intra and interobserver
      variability), sensitivity, and specificity of a simplified noninvasive ultrasound
      methodology for mapping superficial and deep veins of the lower limbs. METHODS:
      62 consecutive patients, aged 62 +/- 11 years, were enrolled. All underwent US
      examinations, performed by two different investigators, of both legs, four
      anatomical parts, and 17 veins, to assess the interobserver variability of
      evaluation of superficial and deep veins of the lower limbs. RESULTS: Overall the
      agreement between the second versus the first operator was very high in detecting
      reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar
      test). The higher CEAP classification stages were significantly associated with
      reflux (odds ratio: 1.778, 95% confidence interval: 1.552-2.038; P < 0.001) as
      well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741-4.389;
      P < 0.001). Thus, our findings show a strict association between the symptoms of
      venous disorders and ultrasound evaluation results for thrombosis or reflux.
      CONCLUSION: This study demonstrated that our venous mapping protocol is a
      reliable method showing a very low interobserver variability, which makes it
      accurate and reproducible for the assessment of the morphofunctional status of
      the lower limb veins.

PMID- 22371653
TI  - Evolving role of platelet function testing in coronary artery interventions.
AB  - The substantial reduction in ischemic events provided by the dual antiplatelet
      regimen with aspirin and clopidogrel is well documented in patients with acute
      coronary syndrome and patients undergoing percutaneous coronary intervention.
      Recently the variable response to the antiplatelet agents has received
      considerable attention after several "boxed warnings" on clopidogrel. This led to
      intense controversy on pharmacokinetic, pharmacodynamic, and pharmacogenomic
      issues of antiplatelet drugs, especially clopidogrel. Research use of platelet
      function testing has been successfully validated in identifying new antiplatelet
      drugs like prasugrel and ticagrelor. These platelet function assays are no longer
      regarded just as a laboratory phenomenon but rather as tools that have been shown
      to predict mortality in several clinical trials. It is believed that suboptimal
      response to an antiplatelet regimen (pharmacodynamic effect) may be associated
      with cardiovascular, cerebrovascular, and peripheral arterial events. There has
      been intense controversy about this variable response of antiplatelet drugs and
      the role of platelet function testing to guide antiplatelet therapy. While the
      importance of routine platelet function testing may be uncertain, it may be
      useful in high-risk patients such as those with diabetes mellitus, diffuse three
      vessels coronary artery disease, left main stenosis, diffuse atherosclerotic
      disease, and those with chronic renal failure undergoing percutaneous coronary
      intervention. It could also be useful in patients with suspected pharmacodynamic
      interaction with other drugs to assure the adequacy of platelet inhibition. While
      we wait for definitive trials, a predictive prognostic algorithm is necessary to
      individualize antiplatelet therapy with P2Y12 inhibitors based on platelet
      function assays and genetic testing.

PMID- 22371654
TI  - Exercise order affects the total training volume and the ratings of perceived
      exertion in response to a super-set resistance training session.
AB  - The super-set is a widely used resistance training method consisting of exercises
      for agonist and antagonist muscles with limited or no rest interval between them 
      for example, bench press followed by bent-over rows. In this sense, the aim of
      the present study was to compare the effects of different super-set exercise
      sequences on the total training volume. A secondary aim was to evaluate the
      ratings of perceived exertion and fatigue index in response to different exercise
      order. On separate testing days, twelve resistance-trained men, aged 23.0 +/- 4.3
      years, height 174.8 +/- 6.75 cm, body mass 77.8 +/- 13.27 kg, body fat 12.0% +/-
      4.7%, were submitted to a super-set method by using two different exercise
      orders: quadriceps (leg extension) + hamstrings (leg curl) (QH) or hamstrings
      (leg curl) + quadriceps (leg extension) (HQ). Sessions consisted of three sets
      with a ten-repetition maximum load with 90 seconds rest between sets. Results
      revealed that the total training volume was higher for the HQ exercise order (P =
      0.02) with lower perceived exertion than the inverse order (P = 0.04). These
      results suggest that HQ exercise order involving lower limbs may benefit
      practitioners interested in reaching a higher total training volume with lower
      ratings of perceived exertion compared with the leg extension plus leg curl
      order.

PMID- 22371655
TI  - Neuropathic diabetic foot ulcers - evidence-to-practice.
AB  - Foot ulcers and their attendant complications are disquietingly high in people
      with diabetes, a majority of whom have underlying neuropathy. This review
      examines the evidence base underpinning the prevention and management of
      neuropathic diabetic foot ulcers in order to inform best clinical practice. Since
      it may be impractical to ask patients not to weight-bear at all, relief of
      pressure through the use of offloading casting devices remains the mainstay for
      management of neuropathic ulcers, whilst provision of appropriate footwear is
      essential in ulcer prevention. Simple non-surgical debridement and application of
      hydrogels are both effective in preparing the wound bed for healthy granulation
      and therefore enhancing healing. Initial empirical antibiotic therapy for
      infected ulcers should cover the most common bacterial flora. There is limited
      evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and
      cytokines or growth factors. In selected cases, recombinant human platelet
      derived growth factor has been shown to enhance healing; however, its widespread
      use cannot be advised due to the availability of more cost-effective approaches.
      While patient education may be beneficial, the evidence base remains thin and
      conflicting. In conclusion, best management of foot ulcers is achieved by what is
      taken out of the foot (pressure, callus, infection, and slough) rather than what
      is put on the foot (adjuvant treatment).

PMID- 22371656
TI  - The discrediting of the monoamine hypothesis.
AB  - BACKGROUND: The monoamine hypothesis has been recognized for over half a century
      as a reference point to understanding electrical dysfunction associated with
      disease states, and/or regulatory dysfunction related to synaptic, centrally
      acting monoamine concentrations (serotonin, dopamine, norepinephrine, and
      epinephrine). METHODS: Organic cation transporters (OCT) are a primary force
      controlling intracellular and extracellular (including synaptic) concentrations
      of centrally acting monoamines and their amino acid precursors. A new type of
      research was analyzed in this paper (previously published by the authors)
      relating to determining the functional status of the nutritionally driven organic
      cation transporters. It was correlated with the claims of the monoamine
      hypothesis. RESULTS: Results of laboratory assays from subjects not suffering
      from a hyperexcreting tumor show that centrally acting monoamine concentrations
      are indistinguishable in subjects with and without disease symptoms and/or
      regulatory dysfunction. Analysis of centrally acting monoamine concentrations in
      the endogenous state reveals a significant difference in day-to-day assays
      performed on the same subject with and without monoamine-related disease symptoms
      and/or regulatory dysfunction. The day-to-day difference renders baseline testing
      in the endogenous state non-reproducible in the same subject. CONCLUSION: It is
      asserted that the monoamine hypothesis, which claims that low synaptic levels of
      monoamines are a primary etiology of disease, is not a valid primary reference
      point for understanding chronic electrical dysfunction related to the centrally
      acting monoamines. Furthermore, the "bundle damage theory" is a more accurate
      primary model for understanding chronic dysfunction. The "bundle damage theory"
      advocates that synaptic monoamine levels are normal but not adequate in states
      associated with chronic electrical dysfunction and that levels need to be
      increased to compensate for the chronic postsynaptic electrical dysfunction due
      to existing damage. The monoamine hypothesis, in failing to accurately explain
      the etiology of chronic neuronal electrical flow dysfunction in the endogenous
      state, is reduced to no more than a historical footnote.

PMID- 22371657
TI  - Perception and utilization of traditional birth attendants by pregnant women
      attending primary health care clinics in a rural Local Government Area in Ogun
      State, Nigeria.
AB  - BACKGROUND: In developing countries, most childbirth occurs at home and is not
      assisted by skilled attendants. This situation increases the risk of death for
      both mother and child and has severe maternal and neonatal health complications.
      The purpose of this study was to explore pregnant women's perceptions and
      utilization of traditional birth attendant (TBA) services in a rural Local
      Government Area (LGA) in Ogun State, southwest Nigeria. METHODS: A quantitative
      design was used to obtain information using a structured questionnaire from 250
      pregnant women attending four randomly selected primary health care clinics in
      the LGA. Data were analyzed using Epi Info (v 3.5.1) statistical software.
      RESULTS: Almost half (48.8%) of the respondents were in the age group 26-35
      years, with a mean age of 29.4 +/- 7.33 years. About two-thirds (65.6%) of the
      respondents had been pregnant 2-4 times before. TBA functions, as identified by
      respondents, were: "taking normal delivery" (56.7%), "providing antenatal
      services" (16.5%), "performing caesarean section" (13.0%), "providing family
      planning services" (8.2%), and "performing gynaecological surgeries" (5.6%).
      About 6/10 (61.0%) respondents believed that TBAs have adequate knowledge and
      skills to care for them, however, approximately 7/10 (69.7%) respondents
      acknowledged that complications could arise from TBA care. Services obtained from
      TBAs were: routine antenatal care (81.1%), normal delivery (36.1%), "special
      maternal bath to ward off evil spirits" (1.9%), "concoctions for mothers to drink
      to make baby strong" (15.1%), and family planning services (1.9%). Reasons for
      using TBA services were: "TBA services are cheaper" (50.9%), "TBA services are
      more culturally acceptable in my environment" (34.0%), "TBA services are closer
      to my house than hospital services" (13.2%), "TBAs provide more compassionate
      care than orthodox health workers" (43.4%), and "TBA service is the only
      maternity service that I know" (1.9%). Approximately 8/10 (79.2%) of the users
      (past or current) opined that TBA services are effective but could be improved
      with some form of training (78.3%). More than three-quarters (77.1%) opposed the
      banning of TBA services. Almost 7/10 (74.8%) users were satisfied with TBA
      services. CONCLUSION: Study findings revealed a positive perception and use of
      TBA services by the respondents. This underlines the necessity for TBAs'
      knowledge and skills to be improved within permissible standards through
      sustained partnership between TBAs and health systems. It is hoped that such
      partnership will foster a healthy collaboration between providers of orthodox and
      traditional maternity services that will translate into improved maternal and
      neonatal health outcomes in relevant settings.

PMID- 22371659
TI  - Female genital mutilation: prevalence, perceptions and effect on women's health
      in Kersa district of Ethiopia.
AB  - BACKGROUND: Female genital mutilation (FGM) is nontherapeutic surgical
      modification of the female genitalia. It is an ancient tradition in large parts
      of Africa, including Ethiopia, especially in the eastern part of the country.
      This study aimed to identify the prevalence, perceptions, perpetuators, reasons
      for conducting FGM, and factors associated with this practice with regard to
      women's health. METHODS: Community-based cross-sectional house-to-house
      interviews were conducted during 2008 among 858 females of reproductive age (15
      49 years), in Kersa district, East Hararge, Oromia region, Ethiopia. Proportions
      and Chi-square tests were used to describe the data and logistic regression was
      used to describe statistical associations. Statistical significance was set at P
      < 0.05. RESULTS: FGM was reported to be known by 327 (38.5%) of the interviewees.
      The majority (n = 249, 76.1%) reported that local healers were the main
      performers of FGM, and 258 (78.9%) respondents stated that the clitoris was the
      part removed during circumcision. The main reason for the practice of FGM was
      reduction of female sexual hyperactivity (reported by 198 women [60.3%]).
      Circumcision of daughters was reported by 288 (88.1%) respondents, and this
      showed a statistically significant association with the Christian religion (P =
      0.003), illiteracy (P = 0.01), and Amhara ethnicity (P = 0.012). The majority of
      the respondents (792, 92.3%) were themselves circumcised and 68.8% did not know
      of any health-related problems associated with FGM. CONCLUSION: In spite of FGM
      being a common practice in the study area, only one third of the respondents
      stated that they knew about it. Local healers were the main performers of FGM.
      Some of the women knew about the negative reproductive health effects of FGM and
      some had also experienced these themselves. However, only a few had tried to stop
      the practice and the majority had taken no steps to do so. This may be
      attributable to the fear of becoming alienated from the cultural system and fear
      of isolation.

PMID- 22371660
TI  - 'Bellography': Life and Contributions of Ross and Joyce Bell, two New England
      Naturalists.
AB  - The lives and contributions of Ross and Joyce Bell are described with particular
      attention to studies of invertebrate natural history in the state of Vermont and
      carabid beetles of several groups, including the world rhysodine fauna. Their
      work, all done at the University of Vermont, was mainly taxonomic in nature and
      included aspects of the biology of the species considered. During their careers
      they described more than 75% of the c. 340 rhysodine species known to science.
      Ross Bell also wrote a number of seminal papers about the basal relationships of
      the Adephaga and the comparative anatomy of carabid coxal cavities. Ross and
      Joyce inspired several generations of students at UVM to take up advanced work in
      entomology and natural history.

PMID- 22371658
TI  - Breast manifestations of systemic diseases.
AB  - Although much emphasis has been placed on the primary presentations of breast
      cancer, little focus has been placed on how systemic illnesses may affect the
      breast. In this article, we discuss systemic illnesses that can manifest in the
      breast. We summarize the clinical features, imaging, histopathology, and
      treatment recommendations for endocrine, vascular, systemic inflammatory,
      infectious, and hematologic diseases, as well as for the extramammary
      malignancies that can present in the breast. Despite the rarity of these
      manifestations of systemic disease, knowledge of these conditions is critical to
      the appropriate evaluation and treatment of patients presenting with breast
      symptoms.

PMID- 22371661
TI  - Ross and joyce bell as mentors at the university of vermont.

PMID- 22371662
TI  - New species of springtails in the Proisotoma genus complex from Vermont and New
      York, USA with descriptive notes on Ballistura alpa Christiansen & Bellinger 1980
      (Hexapoda, Collembola, Isotomidae).
AB  - Three new species of Isotomidae springtails are described from the Lake Champlain
      Basin (Vermont and New York, USA), Lake Willoughby and Greater Averril Pond in
      Vermont. Subisotoma joyceisp. n. and Scutisotoma champisp. n. were collected in
      sandy beaches whereas Ballistura rossisp. n. was found only in a constructed
      wetland built and managed by the University of Vermont. Scutisotoma champisp. n.
      was found in Lakes Champlain and Willoughby, and Greater Averril Pond and is
      probably present in most lakes and large ponds in the area. Subisotoma joyceisp.
      n. was found only along the southern and eastern coast of South Hero, and the
      mainland coast facing eastern South Hero. Ballistura alpa is redescribed and
      transferred to the genus Pachyotoma based on the absence of tibiotarsal seta
      B4/B5, the presence of secondary cuticular granules, 4 prelabral setae, a full
      complement of guard setae on labial papilla E and in having a bifurcate outer
      maxillary lobe with 4 sublobal setae.

PMID- 22371663
TI  - Mandibles and labrum-epipharynx of tiger beetles: basic structure and evolution
      (Coleoptera, Carabidae, Cicindelitae).
AB  - Using for comparison with, and as outgroups for, supertribe Cicindelitae, we
      describe and illustrate the mandibles and labrum-epipharynx of the basal
      geadephagans Trachypachus gibbsii LeConte, 1861 (family Trachypachidae), and
      family Carabidae: Pelophila rudis (LeConte, 1863) (supertribe Nebriitae, tribe
      Pelophilini) and Ceroglossus chilensis (Eschscholtz, 1829) (supertribe Carabitae,
      tribe Ceroglossini). The range and pattern of variation in structure of mandibles
      and labrum-epipharynx within the supertribe Cicindelitae was assessed using
      scanning-electron (SEM) images of these structures in nine exemplar taxa:
      Amblycheila baroni (Rivers, 1890), Omus californicus (Eschscholtz, 1829) and
      Picnochile fallaciosa (Chevrolat, 1854) (representing the Amblycheilini);
      Manticora tuberculata (DeGeer, 1778) (representing the Manticorini): Tetracha
      carolina (Linnaeus, 1767) (representing the Megacephalini); Pogonostoma chalybeum
      (Klug, 1835) (representing the Collyridini); and Therates basalis Dejean, 1826,
      Oxycheila species, and Cicindela longilabris Say, 1824 (representing the
      Cicindelini). An evolutionary transformation series was postulated for the
      mandibles and labrum-epipharynx, based on a reconstructed phylogenetic sequence,
      which, in turn, was based on morphological and DNAevidence.Principal features of
      the transformation series for the mandibles included development of a densely
      setose basal face; wide quadridentate retinaculum; a lengthened incisor tooth; a
      multidentate terebra (one to five teeth; two-three most frequent), followed by
      subsequent loss of one or more such teeth; development of a diastema in the
      occlusal surface; development and subsequent loss of scrobal setae, and reduction
      and loss of the scrobe. Principal features of the transformation series for the
      labrum included evolution of form from transverse, sub-rectangular to elongate
      almost square, to triangular; position and number of setae evolved from dorsal to
      insertion on the apical margin, the number increased from 8-10 to as many as 36,
      and decreased to as few as four. The epipharynx broadened evolutionarily, the
      pedium evolving in form from narrow, triangular and nearly flat, to broad,
      palatiform, and markedly convex; anterior parapedial setae both increased and
      decreased in number, and in orientation, from a row parallel to the parapedial
      ridge to a setal row extended forward at about a right angle to the latter.

PMID- 22371664
TI  - Taxonomic revision of hispaniola tiger beetles in the genus brasiella rivalier
      1954 (coleoptera, carabidae, cicindelinae).
AB  - The Brasiella tiger beetle fauna on Hispaniola, the second largest island of the
      Greater Antilles, has more species diversity than currently recognized as all
      populations previously have been assigned to the insular endemic Brasiella
      dominicana (Mandl). A comparative study of adult morphology, particularly male
      genitalic and female abdominal characters, for available Brasiella specimens from
      populations on Hispaniola, proposes eight additional new species also endemic to
      this island. Except for three sympatric species in the Sierra de Baoruco in
      southern Dominican Republic occurring in different habitats, all the Brasiella on
      Hispaniola appear to be allopatric. Most species occur in the major mountainous
      regions of Hispaniola. Two species, however, are known only from river
      floodplains in the southern coastal plain of the Dominican Republic. Brasiella
      dominicana (Mandl) and Brasiella ocoa, new species, occur along river floodplains
      emanating from the eastern end of the Cordillera Central in the Dominican
      Republic. Two new Brasiella species, Brasiella bellorum, and Brasiella philipi,
      occur in the Cordillera Central, Dominican Republic, the former species from
      central portions, and the latter species from north slopes of this mountain
      range, respectively. Three new Brasiella species, Brasiella rawlinsi, Brasiella
      iviei, and Brasiella youngi, are isolated in the Sierra de Baoruco, Dominican
      Republic, where each occupies a different habitat along an altitudinal gradient.
      The two new Brasiella species in Haiti are Brasiella darlingtoniana, in the
      Massif de la Selle, and Brasiella davidsoni, in the Massif de la Hotte. All nine
      Brasiella species on Hispaniola, along with Brasiella viridicollis (Dejean) and
      its two subspecies on Cuba, belong to the viridicollis species group of the genus
      Brasiella based on criteria presented in earlier published phylogenetic studies
      of Brazilian and West Indian tiger beetles. The subspecies Brasiella viridicollis
      fernandozayasi (Kippenhan, Ivie and Hopp) may represent a distinct species within
      this species group, whereas removal of Brasiella wickhami (W. Horn) from this
      species group seems warranted based on evidence presented. A general overview of
      species relationships for the Brasiella on Hispaniola are discussed, along with
      the current and ancestral geographic distributions of the Brasiella viridicollis
      species group in the West Indies.

PMID- 22371666
TI  - A new species of Bembidion Latrielle 1802 from the Ozarks, with a review of the
      North American species of subgenus Trichoplataphus Netolitzky 1914 (Coleoptera,
      Carabidae, Bembidiini).
AB  - A new species of Bembidion (Trichoplataphus Netolitzky) from the Ozark Plateau of
      Missouri and Arkansas is described (Bembidion ozarkense Maddison and
      Hildebrandt). It is distinguishable from the closely related species, Bembidion
      rolandi Fall, by characteristics of the male genitalia, and sequences of the
      genes cytochrome oxidase I and 28S ribosomal DNA. A brief review of the North
      American species of Trichoplataphus is presented, including a key to species.

PMID- 22371665
TI  - The evolution and age of populations of Scaphinotus petersi Roeschke on Arizona
      Sky Islands (Coleoptera, Carabidae, Cychrini).
AB  - Populations of the ground beetle Scaphinotus petersi are isolated in subalpine
      conifer forest habitats on mountain ranges or Sky Islands in southeastern
      Arizona. Previous work on this species has suggested these populations have been
      isolated since the last post-glacial maximum times as warming caused this cool
      adapted species to retreat to high elevations. To test this hypothesis, we
      inferred the phylogeny from mitochondrial DNA sequence data from several Arizona
      Sky Island populations of Scaphinotus petersi and estimated the divergence time
      of the currently isolated populations. We found two major clades of Scaphinotus
      petersi, an eastern clade and a western group. Our results indicated most
      mountain ranges form clades except the Huachucas, which are polyphyletic and the
      Santa Catalinas, which are paraphyletic. We estimated the Pinaleno population is
      much older than the last glacial maximum, but the Huachuca and Pinal populations
      may have been fragmented from the Santa Catalina population since the post
      glacial maximum times.

PMID- 22371667
TI  - Cladistic assessment of subtribal affinities within the tribe Moriomorphini with
      description of Rossjoycea glacialis, gen. n. and sp. n. from the South Island,
      and revision of Meonochilus Liebherr and Marris from the North Island, New
      Zealand (Coleoptera, Carabidae).
AB  - Phylogenetic relationships within the tribe Moriomorphini Sloane, 1890 are
      analyzed cladistically based on 75 morphological characters and 21 ingroup
      terminal taxa rooted at a Trechus obtusus Erichson outgroup. Based on the
      resultant cladistic relationships, two subtribes-Moriomorphina and Amblytelina
      Blackburn, 1892-are recognized, with the following new synonymies proposed:
      Meonides Sloane, 1898 = Amblytelina (NEW SYNONYMY); Tropopterides Sloane, 1898 =
      Amblytelina (NEW SYNONYMY); Mecyclothoracitae Jeannel, 1940 = Amblytelina (NEW
      SYNONYMY). Monophyly of Moriomorphina is based on presence of elongate, parallel
      sided and glabrous to nearly glabrous male parameres, whereas Amblytelina are
      defined most broadly by possession of conchoid parameres with narrowed, setose
      apices, subtending a clade defined by a more derived parameral configuration
      whereby elongate styloid parameres terminate in a whip-like apical extension.
      Representatives of all New Zealand moriomorphine genera are included in the
      analysis, with cladistic results necessitating description of Rossjoycea
      glacialis, gen. n. and sp. n., known from a single locality near the Franz Josef
      Glacier, Westland, South Island, New Zealand. Monophyly of Meonochilus Liebherr
      and Marris, 2009 is demonstrated, and its six species are taxonomically revised:
      Meonochilus amplipennis (Broun), Meonochilus eplicatus (Broun), Meonochilus
      placens (Broun), Meonochilus bellorum, sp. n., Meonochilus rectus, sp. n., and
      Meonochilus spiculatus, sp. n. Geographic restriction of Meonochilus to the North
      Island of New Zealand, coupled with its sister-group status to an Australian
      based Amblytelus Erichson-Mecyclothorax Sharp clade reinforce the interpretation
      that Meonochilus was isolated in New Zealand by vicariance along the Norfolk
      Ridge, subsequent to New Zealand's initial Cretaceous isolation from Tasmania and
      southeastern Australia via opening of the Tasman Sea.

PMID- 22371668
TI  - Taxonomic review of the Pterostichini and Loxandrini fauna of New Caledonia
      (Coleoptera, Carabidae).
AB  - The generic-level taxa included in Pterostichini and Loxandrini from New
      Caledonia are reviewed and a key to genera and species provided. Two new genera
      are described, Paniestichus and Abacophrastus, with the following new species:
      Paniestichus subsolianus, Abacophrastus millei, Abacophrastus chapes,
      Abacophrastus carnifex, Abacophrastus hobbit, Abacophrastus megalops,
      Abacophrastus reflexus and Abacophrastus bellorum. Abacoleptus curtus new
      species, is described. Notonomus irideus and Notonomus savesi are moved to
      Prosopogmus. Four new species of Prosopogmus are described: Prosopogmus
      koghisensis, Prosopogmus lescheni, Prosopogmus fortis and Prosopogmus
      aoupiniensis. Homalosoma griseolum is moved to Sphodrosomus. Cerabilia is newly
      recorded from New Caledonia and the genus is moved from Platynini to Loxandrini
      and therefore is the first report of Loxandrini from New Caledonia. An apparent
      adventive from Australia, Darodilia, is newly reported from New Caledonia.

PMID- 22371669
TI  - Badister Clairville 1806: A new species and new continental record for the
      nominate subgenus in Amazonian Peru (Coleoptera, Carabidae, Licinini).
AB  - Badister (Badister) amazonussp. n. is described from Peru, Loreto, 1.0 km SW Boca
      del Rio Samiria, Vigilante Post 1, 130m, "04 degrees 40.5'S, 074 degrees 18.9'W"
      its type locality. It is known also from two other localities in Loreto
      Department, Peru, in both the Varzea and Igapo river systems. This new species is
      sufficiently different that a new informal higher taxon, the amazonus species
      complex, is recognized. An updated key to the Western Hemisphere species of
      subgenus Badister is provided.

PMID- 22371670
TI  - Pseudaptinus (Thalpius) nobilis Liebke, new to the United States, and a key to
      the species of subgenus Thalpius LeConte in North America, including Mexico
      (Coleoptera, Carabidae, Zuphiini).
AB  - The Mexican carabid species Pseudaptinus (Thalpius) nobilis Liebke is documented
      from the United States for the first time based on two specimens captured in
      southeastern Texas. A new taxonomic key distinguishes the 10 members of subgenus
      Thalpius known in North America, including Mexico. Pseudaptinus (Thalpius)
      dorsalis, which is found to be highly variable in its dorsal coloration, is
      compared to similar Pseudaptinus (Thalpius) hoegei. Geographic ranges are
      extended for several species.

PMID- 22371671
TI  - A taxonomic revision of the New World genus Oropodes Casey (Coleoptera,
      Staphylinidae, Pselaphinae).
AB  - The genus Oropodes is characterized and revised with 18 species being treated.
      Members of this genus are found in temperate forests to desert brush lands from
      Oregon to Baja California, but are associated primarily with dry forests and
      shrub lands of California. Keys to males and females, where known, are provided.
      Seven species are redescribed: Oropodes arcaps (California), Oropodes dybasi
      (Oregon), Oropodes ishii (California), Oropodes nuclere (California), Oropodes
      orbiceps (California), Oropodes rumseyensis (California), Oropodes yollabolly
      (California). The name Oropodes raffrayi (California) is raised from synonymy and
      the species is redescribed, NEW STATUS. Ten new species are described: Oropodes
      aalbui (California), Oropodes bellorum (California), Oropodes casson
      (California), Oropodes chumash (California), Oropodes esselen (California),
      Oropodes hardyi (California), Oropodes serrano (California), Oropodes tataviam
      (California), Oropodes tongva (California), and Oropodes tipai (Baja California,
      Mexico), NEW SPECIES. These species are placed into three species groups: the
      arcaps-group, the orbiceps-group, and the raffrayi-group. Data for a new record
      of Euplecterga fideli are given, and a list of the unassociated Oropodes females
      with distinctive genitalia is included with their label data.

PMID- 22371672
TI  - Biology needs cyberinfrastructure to facilitate specimen-level data acquisition
      for insects and other hyperdiverse groups.

PMID- 22371673
TI  - Carabid beetle diversity and distribution in Boston Harbor Islands national park
      area (Coleoptera, Carabidae).
AB  - As part of an All Taxa Biodiversity Inventory in Boston Harbor Islands national
      park area, an inventory of carabid beetles on 13 islands was conducted. Intensive
      sampling on ten of the islands, using an assortment of passive traps and limited
      hand collecting, resulted in the capture of 6,194 specimens, comprising 128
      species. Among these species were seven new state records for Massachusetts
      (Acupalpus nanellus,Amara aulica,Amara bifrons, Apenes lucidulus, Bradycellus
      tantillus, Harpalus rubripes and Laemostenus terricola terricola-the last also a
      new country record; in passing we report also new state records for Harpalus
      rubripes from New York and Pennsylvania, Amara ovata from Pennsylvania, and the
      first mainland New York records for Asaphidion curtum). For most islands, there
      was a clear relationship between species richness and island area. Two islands,
      however, Calf and Grape, had far more species than their relatively small size
      would predict. Freshwater marshes on these islands, along with a suite of
      hygrophilous species, suggested that habitat diversity plays an important role in
      island species richness. Introduced species (18) comprised 14.0% of the total
      observed species richness, compared to 5.5% (17 out of 306 species) documented
      for Rhode Island. We surmise that the higher proportion of introduced species on
      the islands is, in part, due to a higher proportion of disturbed and open
      habitats as well as high rates of human traffic. We predict that more active
      sampling in specialized habitats would bring the total carabid fauna of the
      Boston Harbor Islands closer to that of Rhode Island or eastern Massachusetts in
      richness and composition; however, isolation, human disturbance and traffic, and
      limited habitat diversity all contribute to reducing the species pool on the
      islands relative to that on the mainland.

PMID- 22371674
TI  - Nebria brevicollis (Fabricius, 1792) in North America, benign or malign?
      (Coleoptera, Carabidae, Nebriini).
AB  - Nebria brevicollis (Fabricius) is one of the most frequently encountered and
      widely distributed carabid beetles in Europe. Until recently, the only North
      American records were based on two single specimens, both from the 1930's in
      southeastern Canada. In 2008, this species was found at thirteen different sites
      in five counties in northwestern Oregon. As of the end of 2010, it has been found
      in thirty-four different sites in ten Oregon counties, with a north-south range
      of ~150 km and an east-west range of ~90 km. It was also detected in 2010 in
      southwestern Washington (Vancouver), just north of Portland and the Columbia
      River.The ecological amplitude of Nebria brevicollis in Oregon rivals that of the
      most eurytopic native carabid species, e.g., Pterostichus algidus LeConte and
      Scaphinotus marginatus (Fischer von Waldheim). It has been found in highly
      degraded heavy industrial sites, agricultural fields, city parks, gardens, second
      growth woodlands, mature conifer forests, montane rock gardens, and otherwise
      pristine stands of old growth noble fir, with elevations ranging from essentially
      sea level to 1,249 meters. Climates at these locales vary from that of the
      Mediterranean Willamette Valley floor, where snow rarely occurs and summers are
      hot and dry, to the summit of the Oregon Coast Range, where deep snow may be
      present from November through April and summers are cool. The carabid communities
      in which Nebria brevicollis has been found range from those predominantly of
      fellow exotic species, e.g., at heavily perturbed sites, to those where it is the
      only exotic species, such as at the Coast Range summit.Nebria brevicollis is
      clearly an invasive species in that it is not restricted to anthropogenic
      habitats, is rapidly expanding its North American range, and can be abundant in
      essentially pristine settings. What is not yet clear is whether it is or will
      become a damaging species. Although it is already the most abundant carabid
      species in some settings, based upon pitfall catches, it is unknown whether this
      represents competitive superiority, trap vulnerability, or utilization of
      previously untapped or non-limiting resources. Deleterious ecological effects
      could include not only competition with other predators (including other carabid
      species) in agricultural and natural settings but also predation upon non-adult
      stages of threatened and endangered species of butterflies.

PMID- 22371675
TI  - Tabanidae and other Diptera on Camel's Hump Vermont: Ecological Observations.
AB  - A canopy trap and aerial nets led to finding 8 species of Tabanidae. There was an
      abundance of calyptrate muscoid flies. Camel's Hump is in the Green Mountains of
      western New England, USA. Discovering Diptera on Camel's Hump involved sixteen
      visits over 40 years. Upwards of 23 other Diptera species are listed. Habitats on
      the east side and above 762 m (2500 ft) elevation on Camel's Hump differ from the
      west slope but the boreal forest on both sides is influenced by cloud and fog
      precipitation on trees. The cliffs just above the 900 m level along the east side
      are often overlooked, are not seen from the summit and provide access to morning
      sun for insects. Recent visits explored the role of polarized skylight in
      relation to the canopy trap, the boreal forest environment and flies found there.

PMID- 22371676
TI  - Landscape patterns of species-level association between ground-beetles and
      overstory trees in boreal forests of western Canada (Coleoptera, Carabidae).
AB  - Spatial associations between species of trees and ground-beetles (Coleoptera:
      Carabidae) involve many indirect ecological processes, likely reflecting the
      function of numerous forest ecosystem components. Describing and quantifying
      these associations at the landscape scale is basic to the development of a
      surrogate-based framework for biodiversity monitoring and conservation. In this
      study, we used a systematic sampling grid covering 84 km(2) of boreal mixedwood
      forest to characterize the ground-beetle assemblage associated with each tree
      species occurring on this landscape. Projecting the distribution of relative
      basal area of each tree species on the beetle ordination diagram suggests that
      the carabid community is structured by the same environmental factors that
      affects the distribution of trees, or perhaps even by trees per se. Interestingly
      beetle species are associated with tree species of the same rank order of
      abundance on this landscape, suggesting that conservation of less abundant trees
      will concomitantly foster conservation of less abundant beetle species. Landscape
      patterns of association described here are based on characteristics that can be
      directly linked to provincial forest inventories, providing a basis that is
      already available for use of tree species as biodiversity surrogates in boreal
      forest land management.

PMID- 22371677
TI  - Changes in ground beetle diversity and community composition in age structured
      forests (Coleoptera, Carabidae).
AB  - We examined diversity, community composition, and wing-state of Carabidae as a
      function of forest age in Piedmont North Carolina. Carabidae were collected
      monthly from 396 pitfall traps (12*33 sites) from March 2009 through February
      2010, representing 5 forest age classes approximately 0, 10, 50, 85, and 150
      years old. A total of 2,568 individuals, representing 30 genera and 63 species,
      were collected. Carabid species diversity, as estimated by six diversity indices,
      was significantly different between the oldest and youngest forest age classes
      for four of the six indices. Most carabid species were habitat generalists,
      occurring in all or most of the forest age classes. Carabid species composition
      varied across forest age classes. Seventeen carabid species were identified as
      potential candidates for ecological indicators of forest age. Non-metric
      multidimensional scaling (NMDS) showed separation among forest age classes in
      terms of carabid beetle community composition. The proportion of individuals
      capable of flight decreased significantly with forest age.

PMID- 22371678
TI  - Response of female beetles to LIDAR derived topographic variables in Eastern
      boreal mixedwood forests (Coleoptera, Carabidae).
AB  - Biodiversity monitoring is increasingly being bolstered with high resolution data
      derived from remote sensing such as LIDAR (Light Detection and Ranging). We
      derived a series of topographical variables, including slope, azimuth, ground
      curvature and flow accumulation from LIDAR images and compared these to captures
      of female carabids in pitfall traps in Eastern boreal mixedwood forests. We
      developed a series of species-specific logistic models predicting the proportion
      of females for eight dominant species, including Agonum retractum, Calathus
      ingratus, Platynus decentis, Pterostichus adstrictus, Pterostichus coracinus,
      Pterostichus pensylvanicus, Sphaeroderus nitidicollis and Synuchus impunctatus.
      We used these models to test three hypotheses related to how the modest
      topography in boreal forests could influence the availability of microhabitats
      and possibly potential sites for oviposition and larval development. In general,
      topographic features such as north facing slopes and high flow accumulation were
      important predictors of the proportion of females. Models derived from larger
      scale topography, such as hillsides or small watersheds on the order of 1/4-1 ha
      were better predictors of the proportion of females than were models derived from
      finer scale topography such as hummocks and small depressions. We conclude that
      topography likely influences the distribution of carabids based on hydrological
      mechanisms rather than factors related to temperature. We further suggest based
      on the scale of responses that these hydrological mechanisms may be linked to the
      attenuation of past disturbances by wildfire and the propensity of unburned
      forest patches and fire skips.

PMID- 22371679
TI  - Low intensity surface fire instigates movement by adults of Calosoma frigidum
      (Coleoptera, Carabidae).
AB  - The genus Calosoma (Coleoptera: Carabidae) is a group of large, sometimes ornate
      beetles, which often voraciously attack caterpillars. Many studies have reported
      Calosoma beetles being highly conspicuous during defoliator outbreaks. Based on
      observations of individual beetle behavior, patterns of activity density and
      phenology we provide a hypothesis on how environmental cues may synchronize
      Calosoma activity with periods of high defoliation. We have observed that adults
      of Calosoma frigidum construct underground burrows similar to those reported to
      be created by larvae for pupation. We propose that small increases in soil
      surface temperature caused either by defoliation events or decreased albedo of
      blackened, burned soil causes beetles to leave their underground burrows and
      begin foraging. Indirect support for this hypothesis comes from high levels of
      adult Calosoma frigidum collected in relatively small patches of burned forest
      (<200m(2)) relative to the surrounding mosaic of unburned forest shortly after a
      prescribed surface burn.

PMID- 22371680
TI  - Carabidae diversity along an altitudinal gradient in a Peruvian cloud forest
      (Coleoptera).
AB  - Carabid beetles were sampled at five sites, ranging from 1500 m to 3400 m, along
      a 15 km transect in the cloud forest of Manu National Park, Peru. Seasonal
      collections during a one year period yielded 77 morphospecies, of which 60% are
      projected to be undescribed species. There was a significant negative correlation
      between species richness and altitude, with the number of carabid species
      declining at the rate of one species for each 100 m increase in altitude. The
      majority of species (70.1 %) were restricted to only one altitudinal site and no
      species was found at more than three of the five altitudinal sites. Only one
      genus, Pelmatellus (Tribe Harpalini), was found at all five sites. Active (hand)
      collections yielded approximately twice as many species per individuals collected
      than passive (pitfall trap) collections. This study is the first systematic
      sampling ofcarabid beetles of a high altitude gradient in the cloud forests of
      southeastern Peru and supports the need to conserve the zone of extremely high
      biodiversity present on the eastern slopes of the Peruvian Andes.

PMID- 22371681
TI  - A quarter of a century succession of epigaeic beetle assemblages in remnant
      habitats in an urbanized matrix (Coleoptera, Carabidae).
AB  - We studied the long-term (23-24 years) species turnover and succession of
      epigaeic beetle assemblages (Coleoptera: Carabidae, incl. Cicindelinae) in three
      remnant habitats [cottonwood (Populus spp.) and oak (Quercus spp.) stands, and
      old fields] that are embedded within highly urbanized areas in central Minnesota.
      A total of 9,710 beetle individuals belonging to 98 species were caught in three
      sampling years: 1980, 1981 and 2005 in pitfall traps in identical locations
      within each habitat. Results indicate that there were 2-3 times greater trap
      catches in 2005 than in 1980 (cottonwood and oak stands, and old fields) and 1.4
      1.7 times greater species diversity of beetles in 2005 than in the 1980-1981
      suggesting increased habitat association by beetles over time. Although there
      were no significant differences in catches between 2005 and 1981 (only cottonwood
      stands and old fields), there was a trend where more beetles were caught in 2005.
      At the species-level, 10 times more of an open-habitat carabid species,
      Cyclotrachelus sodalis sodalis LeConte, was caught in 2005 than in 1980. However,
      trap catches of five other abundant carabid species [Pterostichus novus Straneo,
      Platynus decentis (Say), Platynus mutus (Say), Calathus gregarius (Say), and
      Poecilus lucublandus lucublandus (Say)] did not change indicating population
      stability of some beetle species. These remnant habitats were increasingly
      colonized by exotic carabid species as Carabus granulatus granulatus Linneaus,
      Clivina fossor (Linneaus) and Platynus melanarius (Illiger), that were trapped
      for the first time in 2005. Species composition of epigaeic beetles was quite
      distinct in 2005 from 1980 with 39 species reported for the first time in 2005,
      indicating a high turnover of assemblages. At the habitat-level, greatest species
      diversity was in cottonwood stands and lowest was in old fields, and all habitat
      types in 2005 diverged from those in 1980s, but not cottonwood stands in 1981. As
      our sampled areas are among some of the last remnants of the original oak savanna
      habitats in central Minnesota, we hypothesize that conservation of these sites
      may be critical to maintaining epigaeic beetle assemblages under increased
      urbanization pressure.

PMID- 22371682
TI  - A new species of Ripipteryx from Belize with a key to the species of the
      Scrofulosa Group (Orthoptera, Ripipterygidae).
AB  - A new species of the genus Ripipteryx (Orthoptera: Tridactyloidea:
      Ripipterygidae) from the Toledo District of southern Belize is described and
      illustrated. Ripipteryx mopanasp. n. is placed in the Scrofulosa Group based on
      its elaborately ornamented frons and is readily distinguished from its congeners
      by the fusion of the superior and inferior frontal folds to form a nasiform
      median process, the epiproct with both anterior and posterior margins emarginate,
      the subgenital plate with distinct lateroapical depressions either side of the
      median line, the basal plate of the phallus strongly bilobed apically, and the
      development of well-demarcated denticular lobes in the dorsal endophallic valves.
      A preliminary key to the species of the Scrofulosa Group is provided.

PMID- 22371683
TI  - A new species of Orobdella (Hirudinida, Arhynchobdellida, Gastrostomobdellidae)
      and redescription of Orobdella kawakatsuorum from Hokkaido, Japan with the
      phylogenetic position of the new species.
AB  - A new quadrannulate Orobdella Oka, 1895 species, Orobdella koikeisp. n., is
      described on the basis of six specimens collected from Hokkaido, Japan. In
      addition, an emended description of quadrannulate Orobdella kawakatsuorum
      Richardson, 1975 is also provided. Orobdella koikei differs from other
      quadrannulate species of Orobdella in possessing the following combination of
      characters: color dorsally brown, IV uniannulate, male gonopore at XI b6,
      gastropore and female gonopore at XIII a1, 1/2 + 4 + 1/2 between gonopores, XXV
      triannulate, tubular but bulbous at junctions with gastropore and crop
      gastroporal duct, epididymides in XVII to XIX, and atrial cornua ovate. The
      phylogenetic position of the newly described species is estimated using
      mitochondrial COI, tRNA(Cys), tRNA(Met), 12S rDNA, tRNA(Val) and 16S rDNA
      markers. Orobdella koikei is a sister taxon of Orobdella kakawatsuorum according
      to the molecular phylogenetic analyses.

PMID- 22371684
TI  - First record of the genus Phradis Forster (Hymenoptera, Ichneumonidae,
      Tersilochinae) from the Neotropical Region.
AB  - One new species of the genus Phradis, Phradis peruvianussp. n., from the
      mountainous part of Peruvian Amazonia, is described and illustrated. This is the
      first record of the genus from South America and the Neotropical region.

PMID- 22371685
TI  - New species of Plectrocnemia and Nyctiophylax (Trichoptera, Polycentropodidae)
      from China.
AB  - Four new species of genus Plectrocnemia and 4 new species of genus Nyctiophylax
      are described, namely: Plectrocnemia verticalissp. n.; Plectrocnemia acuminatasp.
      n.; Plectrocnemia cryptoparameresp. n.; Plectrocnemia qianshanensissp. n.;
      Nyctiophylax (Nyctiophylax) senticosussp. n.; Nyctiophylax (Paranyctiophylax)
      gracilissp. n.; Nyctiophylax (Paranyctiophylax) pungenssp. n.; and Nyctiophylax
      (Paranyctiophylax) auriculatussp. n.

PMID- 22371686
TI  - Notes on the Stenus cirrus group, with description of two new species from China
      (Coleoptera, Staphylinidae).
AB  - Two new species, Stenus zhangdinghengisp. n., Stenus maoershanussp. n.,of the
      Stenus cirrus group are described from South China, Guangxi Province. The male of
      Stenus fellowesi Puthz, 2003 and the female of Stenus huanghaoi Tang & Li, 2008
      were discovered for the first time. Their diagnostic characters are illustrated
      and a key to the Chinese species of the Stenus cirrus group is provided.

PMID- 22371687
TI  - From text to structured data: Converting a word-processed floristic checklist
      into Darwin Core Archive format.
AB  - The paper describes a pilot project to convert a conventional floristic
      checklist, written in a standard word processing program, into structured data in
      the Darwin Core Archive format. After peer-review and editorial acceptance, the
      final revised version of the checklist was converted into Darwin Core Archive by
      means of regular expressions and published thereafter in both human-readable form
      as traditional botanical publication and Darwin Core Archive data files. The data
      were published and indexed through the Global Biodiversity Information Facility
      (GBIF) Integrated Publishing Toolkit (IPT) and significant portions of the text
      of the paper were used to describe the metadata on IPT. After publication, the
      data will become available through the GBIF infrastructure and can be re-used on
      their own or collated with other data.

PMID- 22371688
TI  - Checklist of vascular plants of the Department of Neembucu, Paraguay.
AB  - The Department of Neembucu is one of the least well-documented areas of eastern
      Paraguay, and the flora is composed of a mixture of forest and Chaco elements.
      Regions like Neembucu are often considered of lower diversity and interest that
      more forested regions; this results from both actual species richness figures and
      from under-collecting due to perception as uninteresting. We present here a
      checklist of the vascular plants of Neembucu, which includes 676 taxa (including
      infraspecific taxa and collections identified only to genus) in 100 families and
      374 genera. Four hundred and thirty nine (439) of these are new records for
      Neembucu and of these, 4 are new published records for Paraguay. Synonyms,
      distribution details within Paraguay and a voucher specimen or literature record
      are provided for each taxon, and a brief analysis of the diversity and importance
      of the flora is presented.

PMID- 22371689
TI  - Speciation and extinction drive the appearance of directional range size
      evolution in phylogenies and the fossil record.
AB  - While the geographic range of a species is a fundamental unit of macroecology and
      a leading predictor of extinction risk, the evolutionary dynamics of species'
      ranges remain poorly understood. Based on statistical associations between range
      size and species age, many studies have claimed support for general models of
      range evolution in which the area occupied by a species varies predictably over
      the course of its life. Such claims have been made using both paleontological
      data and molecular estimates of the age of extant species. However, using a
      stochastic model, we show that the appearance of trends in range size with
      species' age can arise even when range sizes have evolved at random through time.
      This occurs because the samples of species used in existing studies are likely to
      be biased with respect to range size: for example, only those species that
      happened to have large or expanding ranges are likely to survive to the present,
      while extinct species will tend to be those whose ranges, by chance, declined
      through time. We compared the relationship between the age and range size of
      species arising under our stochastic model to those observed across 1,269 species
      of extant birds and mammals and 140 species of extinct Cenozoic marine mollusks.
      We find that the stochastic model is able to generate the full spectrum of
      empirical age-area relationships, implying that such trends cannot be simply
      interpreted as evidence for models of directional range size evolution. Our
      results therefore challenge the theory that species undergo predictable phases of
      geographic expansion and contraction through time.

PMID- 22371690
TI  - Leading multi-professional teams in the children's workforce: an action research
      project.
AB  - INTRODUCTION: The 2004 Children Act in the UK saw the introduction of integrated
      working in children's services. A raft of change followed with processes designed
      to make joint working easier, and models and theories to support the development
      of integrated work. This paper explores the links between key concepts and
      practice. METHODS: A practitioner action research approach is taken using an
      autoethnographic account kept over six months. The research question was, to what
      extent is this group collaborating? RESULTS: When the architecture of practice
      was revealed, differences between espoused and real practice could be seen.
      Whilst understanding and displaying the outward signs of an effective multi
      professional group, the individuals did not trust one another. This was exhibited
      by covert interprofessional issues. As a result, collaborative inertia was
      achieved. This realisation prompted them to participate in further developmental
      and participative action research. CONCLUSION: The paper concludes that trust and
      relational agency are central to effective leadership of multi professional
      teams.

PMID- 22371691
TI  - An empirical investigation of the efficiency effects of integrated care models in
      Switzerland.
AB  - INTRODUCTION: This study investigates the efficiency gains of integrated care
      models in Switzerland, since these models are regarded as cost containment
      options in national social health insurance. These plans generate much lower
      average health care expenditure than the basic insurance plan. The question is,
      however, to what extent these total savings are due to the effects of selection
      and efficiency. METHODS: The empirical analysis is based on data from 399,274
      Swiss residents that constantly had compulsory health insurance with the Helsana
      Group, the largest health insurer in Switzerland, covering the years 2006-2009.
      In order to evaluate the efficiency of the different integrated care models, we
      apply an econometric approach with a mixed-effects model. RESULTS: Our
      estimations indicate that the efficiency effects of integrated care models on
      health care expenditure are significant. However, the different insurance plans
      vary, revealing the following efficiency gains per model: contracted capitated
      model 21.2%, contracted non-capitated model 15.5% and telemedicine model 3.7%.
      The remaining 8.5%, 5.6% and 22.5%, respectively, of the variation in total
      health care expenditure can be attributed to the effects of selection.
      CONCLUSIONS: Integrated care models have the potential to improve care for
      patients with chronic diseases and concurrently have a positive impact on health
      care expenditure. We suggest policy-makers improve the incentives for patients
      with chronic diseases within the existing regulations providing further potential
      for cost-efficiency of medical care.

PMID- 22371692
TI  - Measuring the quality of interprofessional collaboration in child mental health
      collaborative care.
AB  - OBJECTIVE: This pilot study examines the potential utility of the Perception of
      Interprofessional Collaboration Model and the shared decision-making scales in
      evaluating the quality of partnership in child mental health collaborative care.
      METHODS: Ninety-six primary care professionals working with children and youth
      responded to an internet survey which included the Perception of
      Interprofessional Collaboration Model scale (PINCOM-Q) and an adapted version of
      a shared decision-making scale (Echelle de confort decisionnel, partenaire-ECD
      P). The perceptions of child mental health professionals were compared with those
      of other professionals working with children. RESULTS: The PINCOM-Q and the ECD-P
      scales had an excellent internal consistency and they were moderately correlated.
      Child mental health professionals' Individual Interprofessional Collaboration
      scores from the PINCOM-Q individual aspects subscale were better than that of
      other child professionals. CONCLUSION: These scales may be interesting
      instruments to measure the quality of partnership in child mental health
      collaborative care settings. Research needs to replicate these findings and to
      determine whether the quality of collaboration is a predictor of mental health
      outcome.

PMID- 22371694
TI  - Key lessons from integrated care in Europe.

PMID- 22371693
TI  - Factors predicting a successful post-discharge outcome for individuals aged 80
      years and over.
AB  - INTRODUCTION AND BACKGROUND: The early post-discharge period is a vulnerable time
      for older patients with complex care requirements. This paper identifies factors
      predicting a self-reported successful post-discharge outcome for patients aged 80
      years and over by exploring factors related to the discharge process, the
      provision of formal home-care services, informal care and characteristics of the
      patients. METHODS: The study reports results from survey interviews with patients
      admitted from home to 14 hospitals in Norway and later discharged home. Logistic
      regression analysis was performed to assess the impact of a number of factors on
      the likelihood that the patients would report that they managed well after
      discharge. RESULTS: The odds of managing well after discharge were more than four
      times higher (OR=4.75, p=0.022) for patients reporting that someone was present
      at homecoming than for those who came home to an empty house. Patients who
      reported receiving adequate help from the municipality had an odds four times
      (OR=4.18, p=0.006) higher of reporting that everything went well after discharge
      than those who stated the help was inadequate. CONCLUSIONS: Having someone at
      home upon return from hospital and having adequate formal home-care services are
      significantly associated with patient-reported success in managing well.

PMID- 22371695
TI  - Integrated care for older people in Europe-latest trends and perceptions.
AB  - As a researcher and consultant I have coordinated local pilots and European
      research projects to analyse and improve long-term care for older people by
      better integrating health and social care systems. One of my conclusions from the
      wide range of initiatives that have been taken over the past two decades in
      Europe has been the need to treat long-term care as a system in its own right.
      Long-term care systems require a discernable identity; specific policies,
      structures, processes and pathways; and the leadership and resources that can
      underpin expectations, drive performance and achieve better outcomes for people
      that are living with (and working for those with) long-term care needs. Progress
      in developing LTC systems can be identified today in all European countries.
      Integrated care solutions at the interface between health and social care, and
      between formal and informal care, have appeared. These have been achieved partly
      by means of (slow) political reforms, partly as a response to market-oriented
      governance, and in many cases through pioneering community and civil society
      initiatives. It will depend on such initiatives, and their ability to convince
      both citizens and policy-makers, whether new societal approaches to long-term
      care are created that meet the demands of ageing societies.

PMID- 22371696
TI  - Mouse thalamic differentiation: gli-dependent pattern and gli-independent
      prepattern.
AB  - Sonic hedgehog (Shh) signaling is essential for thalamic development. The Gli
      transcription factors act downstream of Shh - while Gli2 is the major activator
      (GliA), Gli3 acts primarily as a repressor (GliR). The thalamus is remarkable
      among dorsal structures because of its proximity to the mid-diencephalic
      organizer, a unique dorsal Shh source. This lends complexity to the interactions
      between Shh, Gli2, and Gli3, suggesting the presence of a dorsal Gli activator
      which elsewhere is found only ventrally, and making the dissection of thalamic
      Gli functions particularly interesting. A current model based on mutant
      phenotypes in telencephalon and midbrain postulates a degree of reciprocal
      antagonism of Shh and Gli3 in dorsal brain regions. To approach the role of Gli
      factors in thalamic specification we first analyzed mice deficient in Gli2 or
      Gli3. In Gli2 mutants, the thalamus is small and poorly differentiated with the
      exception of the medial and intralaminar nuclei which, in contrast, are
      specifically and severely affected by Gli3 inactivation. Gbx2 expression is very
      reduced in the Gli3 mutant. Most thalamic nuclei are present in both mutants,
      although incompletely differentiated, as reflected by the loss of specific
      markers. The ventral posterior group, revealed by novel specific marker Hes1, is
      present in both mutants and extends axons to the telencephalon. To test the
      Gli3/Shh interaction we generated a novel mutant deficient in Gli3 and
      neuroepithelial Shh. The thalamus of the n-Shh/Gli3 double mutants is very large
      and very poorly differentiated except for a broad domain of Gbx2, Lhx2, and Calb2
      expression. In utero electroporation experiments on wild type embryos suggest
      that a stage-specific factor acting early is responsible for this prepattern. We
      show that, in the thalamus, GliA acts downstream of Shh to specify pattern and
      size of the thalamic nuclei to the exception of the medial and intralaminar
      groups. Gli3A can partially substitute for Gli2A in the Gli2 mutant. GliR is
      essential for specification and growth of the medial and intralaminar nuclei,
      contributes to the specification of other thalamic nuclei and reduces thalamic
      size. GliA (from neuroepithelial Shh signaling) and GliR do not show reciprocal
      antagonism in the thalamus, and their joint abolition does not rescue the wild
      type phenotype.

PMID- 22371697
TI  - Interaction of GCAP1 with retinal guanylyl cyclase and calcium: sensitivity to
      fatty acylation.
AB  - Guanylyl cyclase activating proteins (GCAPs) are calcium/magnesium binding
      proteins within neuronal calcium sensor proteins group (NCS) of the EF-hand
      proteins superfamily. GCAPs activate retinal guanylyl cyclase (RetGC) in
      vertebrate photoreceptors in response to light-dependent fall of the
      intracellular free Ca(2+) concentrations. GCAPs consist of four EF-hand domains
      and contain N-terminal fatty acylated glycine, which in GCAP1 is required for the
      normal activation of RetGC. We analyzed the effects of a substitution prohibiting
      N-myristoylation (Gly2 -> Ala) on the ability of the recombinant GCAP1 to co
      localize with its target enzyme when heterologously expressed in HEK293 cells. We
      also compared Ca(2+) binding and RetGC-activating properties of the purified non
      acylated G2A mutant and C14:0 acylated GCAP1 in vitro. The G2A GCAP1 expressed
      with a C-terminal GFP tag was able to co-localize with the cyclase, albeit less
      efficiently than the wild type, but much less effectively stimulated cyclase
      activity in vitro. Ca(2+) binding isotherm of the G2A GCAP1 was slightly shifted
      toward higher free Ca(2+) concentrations and so was Ca(2+) sensitivity of RetGC
      reconstituted with the G2A mutant. At the same time, myristoylation had little
      effect on the high-affinity Ca(2+)-binding in the EF-hand proximal to the
      myristoyl residue in three-dimensional GCAP1 structure. These data indicate that
      the N-terminal fatty acyl group may alter the activity of EF-hands in the distal
      portion of the GCAP1 molecule via presently unknown intramolecular mechanism.

PMID- 22371698
TI  - Dynamic expression of the pro-dopaminergic transcription factors Pax6 and Dlx2
      during postnatal olfactory bulb neurogenesis.
AB  - Olfactory bulb (OB) neurogenesis generates neurons that use GABA or dopamine as
      their neurotransmitters throughout life. Regionalized stem cell populations in
      the periventricular zone (PVZ) of the lateral ventricles (LVs) have been shown to
      be at the basis of neuronal diversity in the system. For example dopaminergic
      neurons arise predominantly from neural stem cells (NSCs) residing in the dorsal
      PVZ and depend on the expression of the transcription factors Pax6 and Dlx2 for
      their specification. In addition, Dlx2 is required for neurogenesis in general.
      Using targeted in vivo electroporation combined with immuno-fluorescence imaging
      and microarray analysis, we provide here detailed spatial and temporal expression
      data with cellular resolution in this system. We find that all along the
      neurogenic process Pax6 expression remains restricted to the dorsal PVZ, whereas
      nearly all neuroblasts express Dlx2, including those of the dorsal lineage, which
      are switched on for Dlx2 when they enter the rostral migratory stream (RMS).
      These data allow to explain and precise the functions of these two genes in
      postnatal OB neurogenesis.

PMID- 22371699
TI  - An ICA with reference approach in identification of genetic variation and
      associated brain networks.
AB  - To address the statistical challenges associated with genome-wide association
      studies, we present an independent component analysis (ICA) with reference
      approach to target a specific genetic variation and associated brain networks.
      First, a small set of single nucleotide polymorphisms (SNPs) are empirically
      chosen to reflect a feature of interest and these SNPs are used as a reference
      when applying ICA to a full genomic SNP array. After extracting the genetic
      component maximally representing the characteristics of the reference, we test
      its association with brain networks in functional magnetic resonance imaging
      (fMRI) data. The method was evaluated on both real and simulated datasets.
      Simulation demonstrates that ICA with reference can extract a specific genetic
      factor, even when the variance accounted for by such a factor is so small that a
      regular ICA fails. Our real data application from 48 schizophrenia patients (SZs)
      and 40 healthy controls (HCs) include 300K SNPs and fMRI images in an auditory
      oddball task. Using SNPs with allelic frequency difference in two groups as a
      reference, we extracted a genetic component that maximally differentiates
      patients from controls (p < 4 * 10(-17)), and discovered a brain functional
      network that was significantly associated with this genetic component (p < 1 *
      10(-4)). The regions in the functional network mainly locate in the thalamus,
      anterior and posterior cingulate gyri. The contributing SNPs in the genetic
      factor mainly fall into two clusters centered at chromosome 7q21 and chromosome
      5q35. The findings from the schizophrenia application are in concordance with
      previous knowledge about brain regions and gene function. All together, the
      results suggest that the ICA with reference can be particularly useful to explore
      the whole genome to find a specific factor of interest and further study its
      effect on brain.

PMID- 22371700
TI  - Global versus local processing: seeing the left side of the forest and the right
      side of the trees.
AB  - Previous studies using hierarchical figures (where a large global shape is
      composed of a series of smaller local shapes) suggest that performance is better
      for local features presented in the right relative to left visual field, whereas
      the opposite pattern is observed for global features. However, these previous
      studies have focused on effects between hemifields. Recent data from patients
      with neurological damage suggest that local deficits can be allocentric (e.g.,
      following left hemisphere injury, individuals are relatively slow to detect
      features on the right side of an object, regardless of visual field). Therefore,
      we decided to extend previous global versus local research by also observing
      local performance within hemifields. Specifically, on each trial we presented two
      hierarchical figures (one in each hemifield), but crucially the left and right
      side of each item were composed of different local features. In this task, the
      participant simply reports if a circle is present, regardless of location or
      whether this is a local or global feature. We observed that both neurologically
      healthy individuals, as well as an individual with brain injury, were relatively
      better detecting local information on the right side of objects, regardless of
      spatial location, while both showed better performance for global stimuli in the
      left visual field. This work is consistent with recent work in patients with
      neurological damage, and provides a new paradigm for exploring hemispheric
      specialization.

PMID- 22371701
TI  - Brain responses in evaluating feedback stimuli with a social dimension.
AB  - Previous studies on outcome evaluation and performance monitoring using gambling
      or simple cognitive tasks have identified two event-related potential (ERP)
      components that are particularly relevant to the neural responses to decision
      outcome. The feedback-related negativity (FRN), typically occurring 200-300 ms
      post-onset of feedback stimuli, encodes mainly the valence of outcome while the
      P300, which is the most positive peak between 200-600 ms, is related to various
      aspects of outcome evaluation. This study investigated the extent to which neural
      correlates of outcome evaluation involving perceptually complex feedback stimuli
      (i.e., female faces) are similar to those elicited by simple feedback. We asked
      participants to judge the attractiveness of blurred faces and then showed them
      unblurred faces as implicit feedback. The FRN effect can be identified in the ERP
      waveforms, albeit in a delayed 300-380 ms time window, with faces inconsistent
      with the initial judgment eliciting more negative-going responses than faces
      consistent with the judgment. However, the ERP waveforms did not show the typical
      pattern of P300 responses. With the principal component analysis (PCA), a clear
      pattern of P300 effects were revealed, with the P300 being more positive to faces
      consistent with the initial judgment than to faces inconsistent with the
      judgment, and more positive to attractive faces than to unattractive ones. The
      effect of feedback consistency did not interact with the effect of attractiveness
      in either the FRN or P300 component. These findings suggest that brain responses
      involved in processing complex feedback stimuli with a social dimension are
      generally similar to those involved in processing simple feedback stimuli in
      gambling or cognitive tasks, although appropriate means of data analysis are
      needed to reveal the typical ERP effects that may have been masked by
      sophisticated cognitive (and emotional) processes for complex stimuli.

PMID- 22371703
TI  - mTOR Inhibition: A Promise for a Young Heart.

PMID- 22371702
TI  - Estradiol treatment prevents injury induced enhancement in spinal cord dynorphin
      expression.
AB  - Administration of the ovarian steroid estradiol in male and female animals has
      been shown to have neuromodulatory and neuroprotective effects in a variety of
      experimental models. In the present study, spinal tissues from dermatomes just
      above (T5-T7, at level) a severe chronic spinal cord injury (SCI) at T8 were
      analyzed for expression levels of prodynorphin (PRDN) and phospho-(serine 369)
      kappa-opioid receptor (KOR-P) in 17 beta estradiol (EB)- and placebo-treated
      adult male rats. Dynorphin was targeted since (1) it has previously been shown to
      be elevated post-SCI, (2) intrathecal injection of dynorphin produces several of
      the same adverse effects seen with a SCI, and (3) its increased expression is
      known to occur in a variety of different experimental models of central
      neuropathic pain. A significant elevation of extracellular levels of both PRDN
      and KOR-P in the placebo-treated SCI group relative to uninjured surgical sham
      controls was found in spinal tissues above the injury level, indicating increased
      dynorphin levels. Importantly, the EB-treated SCI group did not show elevations
      of PRDN levels at 6 weeks post-injury. Immunohistochemical analysis of at level
      tissues revealed that EB treatment significantly prevented a post-SCI increase in
      expression of PRDN puncta co-labeling synapsin I, a nerve terminal marker. The
      dynorphin-containing terminals co-labeled vesicular glutamate receptor-2 (a
      marker of glutamatergic terminals), a finding consistent with a non-opioid basis
      for the adverse effects of dynorphin. These results support a beneficial role for
      EB treatment post-SCI through a reduction in excessive spinal cord levels of
      dynorphin. Studies manipulating the timing of the EB treatment post-injury along
      with specific functional assessments will address whether the beneficial effects
      are due to EB's potential neuromodulatory or neuroprotective action.

PMID- 22371704
TI  - 5'-AMP Activated Protein Kinase is Involved in the Regulation of Myocardial beta
      Oxidative Capacity in Mice.
AB  - 5'-adenosine monophosphate-activated protein kinase (AMPK) is considered central
      in regulation of energy status and substrate utilization within cells. In heart
      failure the energetic state is compromised and substrate metabolism is altered.
      We hypothesized that this could be linked to changes in AMPK activity and we
      therefore investigated mitochondrial oxidative phosphorylation capacity from the
      oxidation of long- and medium-chain fatty acids (LCFA and MCFA) in cardiomyocytes
      from young and old mice expressing a dominant negative AMPKalpha2 (AMPKalpha2-KD)
      construct and their wildtype (WT) littermates. We found a 35-45% (P < 0.05) lower
      mitochondrial capacity for oxidizing MCFA in AMPKalpha2-KD of both age-groups,
      compared to WT. This coincided with marked decreases in protein expression
      (19/29%, P < 0.05) and activity (14/21%, P < 0.05) of 3-hydroxyacyl-CoA
      dehydrogenase (HAD), in young and old AMPKalpha2-KD mice, respectively, compared
      to WT. Maximal LCFA oxidation capacity was similar in AMPKalpha2-KD and WT mice
      independently of age implying that LCFA-transport into the mitochondria was
      unaffected by loss of AMPK activity or progressing age. Expression of regulatory
      proteins of glycolysis and glycogen breakdown showed equivocal effects of age and
      genotype. These results illustrate that AMPK is necessary for normal
      mitochondrial function in the heart and that decreased AMPK activity may lead to
      an altered energetic state as a consequence of reduced capacity to oxidize MCFA.
      We did not identify any clear aging effects on mitochondrial function.

PMID- 22371705
TI  - Non-gaussianity of low frequency heart rate variability and sympathetic
      activation: lack of increases in multiple system atrophy and Parkinson disease.
AB  - The correlates of indices of long-term ambulatory heart rate variability (HRV) of
      the autonomic nervous system have not been completely understood. In this study,
      we evaluated conventional HRV indices, obtained from the daytime (12:00-18:00)
      Holter recording, and a recently proposed non-Gaussianity index (lambda; Kiyono
      et al., 2008) in 12 patients with multiple system atrophy (MSA) and 10 patients
      with Parkinson disease (PD), known to have varying degrees of cardiac vagal and
      sympathetic dysfunction. Compared with the age-matched healthy control group, the
      MSA patients showed significantly decreased HRV, most probably reflecting
      impaired vagal heart rate control, but the PD patients did not show such reduced
      variability. In both MSA and PD patients, the low-to-high frequency (LF/HF) ratio
      and the short-term fractal exponent alpha(1), suggested to reflect the
      sympathovagal balance, were significantly decreased, as observed in congestive
      heart failure (CHF) patients with sympathetic overdrive. In contrast, the
      analysis of the non-Gaussianity index lambda showed that a marked increase in
      intermittent and non-Gaussian HRV observed in the CHF patients was not observed
      in the MSA and PD patients with sympathetic dysfunction. These findings provide
      additional evidence for the relation between the non-Gaussian intermittency of
      HRV and increased sympathetic activity.

PMID- 22371706
TI  - Positive interaction of social comparison and personal responsibility for
      outcomes.
AB  - We formulate and test a model that allows sharp separation between two different
      ways in which environment affects evaluation of outcomes, by comparing social vs.
      private and personal responsibility vs. chance. In the experiment, subjects chose
      between two lotteries, one low-risk and one high-risk. They could then observe
      the outcomes. By varying the environment between private (they could observe the
      outcome of the chosen lottery and the outcome of the lottery they had not chosen)
      and social (they could observe the outcome of the lottery chosen by another
      subject) we can differentiate the response and brain activity following the
      feedback in social and private settings. The evidence suggests that envy and
      pride are significant motives driving decisions and outcomes evaluation, stronger
      than private emotions like regret and rejoice, with ventral striatum playing a
      key role. When we focus on the outcome evaluation stage we demonstrate that BOLD
      signal in ventral striatum is increasing in the difference between obtained and
      counterfactual payoffs. For a given difference in payoffs, striatal responses are
      more pronounced in social than in private environment. Moreover, a positive
      interaction (complementarity) between social comparison and personal
      responsibility is reflected in the pattern of activity in the ventral striatum.
      At decision stage we observe getting ahead of the Joneses effect in ventral
      striatum with subjective value of risk larger in social than in private
      environment.

PMID- 22371707
TI  - Recognition and memory for briefly presented scenes.
AB  - Three times per second, our eyes make a new fixation that generates a new bottom
      up analysis in the visual system. How much is extracted from each glimpse? For
      how long and in what form is that information remembered? To answer these
      questions, investigators have mimicked the effect of continual shifts of fixation
      by using rapid serial visual presentation of sequences of unrelated pictures.
      Experiments in which viewers detect specified target pictures show that detection
      on the basis of meaning is possible at presentation durations as brief as 13 ms,
      suggesting that understanding may be based on feedforward processing, without
      feedback. In contrast, memory for what was just seen is poor unless the viewer
      has about 500 ms to think about the scene: the scene does not need to remain in
      view. Initial memory loss after brief presentations occurs over several seconds,
      suggesting that at least some of the information from the previous few fixations
      persists long enough to support a coherent representation of the current
      environment. In contrast to marked memory loss shortly after brief presentations,
      memory for pictures viewed for 1 s or more is excellent. Although some specific
      visual information persists, the form and content of the perceptual and memory
      representations of pictures over time indicate that conceptual information is
      extracted early and determines most of what remains in longer-term memory.

PMID- 22371708
TI  - Variable stoichiometry and homeostatic regulation of bacterial biomass elemental
      composition.
AB  - Prokaryotic heterotrophs (hereafter, bacteria) represent a large proportion of
      global biomass, and therefore bacterial biomass stoichiometry likely exerts
      control on global phosphorus (P), carbon (C), and nitrogen cycling and primary
      productivity. In this study we grew recently isolated freshwater heterotrophic
      bacteria across an ecologically relevant range of resource C:P ratios (organic C
      to P ratio in available resources) to quantify the P requirements of these
      organisms and examine the degree to which they regulated their P content under P
      sufficient and P-deficient conditions. Bacterial biomass was only limited by P
      when resource C:P was greater than 250 (by atoms). Bacterial C:P ranged from 71
      to 174 under P sufficiency and from 252 to 548 under P deficiency. Bacteria
      exhibited very little C:P homeostasis under P-sufficient growth conditions,
      greater C:P homeostasis under P-deficient conditions, and the ability of bacteria
      to outcompete one another in short-term experiments depended on a tradeoff
      between storing excess P for later use under P-deficient conditions or
      immediately using P to produce more biomass. These results indicate that
      freshwater heterotrophic bacteria are not as P-rich as previously thought and
      that homeostatic regulation of C:P stoichiometry depends on the individual taxa
      and what resource (organic C or available P) is limiting bacterial growth.
      Individual bacterial populations can vary between strong C:P homeostasis under P
      deficiency to virtually no C:P homeostasis under P sufficiency, but variation
      between taxa and the effect this has on competitive ability may dampen the signal
      in C:P(B) at the bacterial community level. Nevertheless, the prevalence of
      homeostatic and non-homeostatic strategies in a bacterial community should have
      important implications for nutrient regeneration and carbon cycling.

PMID- 22371709
TI  - Ser-634 and Ser-636 of Kaposi's Sarcoma-Associated Herpesvirus RTA are Involved
      in Transactivation and are Potential Cdk9 Phosphorylation Sites.
AB  - The replication and transcription activator (RTA) of Kaposi's sarcoma-associated
      herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the
      reactivation process of KSHV latency. By mass spectrometric analysis of affinity
      purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo
      phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear
      localization signal ((527)KKRK(530)) and were previously hypothesized to be
      target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at
      513 and 514 had no effect on K-RTA subcellular localization or transactivation
      activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located
      in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a
      polypeptide with ~10 kDa shorter in molecular weight and reduced transactivation
      in a luciferase reporter assay relative to the wild type. In contrast to
      prediction, the decrease in molecular weight was not due to lack of
      phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA
      and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as
      docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost
      ~30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif,
      indicating that (634)SPSP(637) motif was in vivo phosphorylated. By in vitro
      kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr
      kinase central to transcriptional regulation. Importantly, the capability of K
      RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which
      suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In
      agreement, S634A/S636A mutant exhibited ~25% reduction in KSHV lytic cycle
      reactivation relative to that by the wild type K-RTA. Taken together, our data
      propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host
      transcriptional kinase CDK9 and such a process contributes to a full
      transcriptional potency of K-RTA.

PMID- 22371710
TI  - The effect of preconception paternal alcohol exposure on epigenetic remodeling of
      the h19 and rasgrf1 imprinting control regions in mouse offspring.
AB  - Imprinted loci play a critical role in fetal development. Their expression is
      often regulated by CCCTC-binding factor (CTCF) protein binding at imprinting
      control regions (ICRs). Prenatal alcohol exposure has been shown to reduce global
      DNA methylation in the developing mouse fetus. This study explored the effect of
      preconception paternal alcohol exposure on DNA methylation at two paternally
      methylated ICRs (H19 and Rasgrf1) in the sperm of exposed males and somatic DNA
      of sired offspring. Significant reductions at the H19 CTCF 1 (p = 0.0027) and
      CTCF 2 (p = 0.0009) binding sites were observed in the offspring of ethanol
      treated sires, which was significantly correlated with reduced weight at
      postnatal days 35-42 (p < 0.05). As birth weight was unaffected and growth was
      only delayed during the postnatal weaning period, with subsequent re-convergence,
      we hypothesize that this may be the result of a mental deficit causing delayed
      establishment of independent feeding following weaning and would explain why this
      effect is transient. No difference in DNA methylation was observed in the sperm
      of alcohol-exposed males, indicating that the transmission of the epigenetic
      signal at conception is not due to altered methylation, but may be the result of
      an RNA-mediated mechanism or altered chromatin remodeling.

PMID- 22371712
TI  - The first sport injuries in the history of medicine.
AB  - Medical science is as old as human history and the need for disease treatment.
      Archivists, researchers and historians are collaborating in the project to
      preserve the documentary inheritance and make the medical science useful to the
      public. This research aims to identify and analyze the first registered sport
      injuries in the history of medicine. After a review of the literature, the
      Homeric epics, the texts of the first historical period of ancient Greece, were
      identified and analyzed as the texts which contain the first sport injuries in
      world history.

PMID- 22371711
TI  - Genomic "Dark Matter" in Prostate Cancer: Exploring the Clinical Utility of ncRNA
      as Biomarkers.
AB  - Prostate cancer is the most diagnosed cancer among men in the United States.
      While the majority of patients who undergo surgery (prostatectomy) will
      essentially be cured, about 30-40% men remain at risk for disease progression and
      recurrence. Currently, patients are deemed at risk by evaluation of clinical
      factors, but these do not resolve whether adjuvant therapy will significantly
      attenuate or delay disease progression for a patient at risk. Numerous efforts
      using mRNA-based biomarkers have been described for this purpose, but none have
      successfully reached widespread clinical practice in helping to make an adjuvant
      therapy decision. Here, we assess the utility of non-coding RNAs as biomarkers
      for prostate cancer recurrence based on high-resolution oligonucleotide
      microarray analysis of surgical tissue specimens from normal adjacent prostate,
      primary tumors, and metastases. We identify differentially expressed non-coding
      RNAs that distinguish between the different prostate tissue types and show that
      these non-coding RNAs can predict clinical outcomes in primary tumors. Together,
      these results suggest that non-coding RNAs are emerging from the "dark matter" of
      the genome as a new source of biomarkers for characterizing disease recurrence
      and progression. While this study shows that non-coding RNA biomarkers can be
      highly informative, future studies will be needed to further characterize the
      specific roles of these non-coding RNA biomarkers in the development of
      aggressive disease.

PMID- 22371713
TI  - Effects of drugs on the efficacy of radioiodine (|) therapy in hyperthyroid
      patients.
AB  - The treatment of hyperthyroidism is targeted at reducing the production of
      thyroid hormones by inhibiting their synthesis or suppressing their release, as
      well as by controlling their influence on peripheral tissue (conservative
      therapy, medical treatment). Radical treatment includes surgical intervention to
      reduce the volume of thyroid tissue or damage of the mechanisms of thyroid
      hormone synthesis by radioiodine ((131)|) administration. Radioiodine ((131)|) is
      a reactor radionuclide, produced as a result of uranium decomposition and
      emission of beta and gamma radiation. The therapeutic effects of the isotope are
      obtained by the emission of beta radiation. In the paper, the effects of
      administered drugs (antithyroid, glucocorticosteroids, lithium carbonate,
      inorganic iodine, beta-blockers) on the final outcome of radioiodine therapy in
      patients with hyperthyroidism are discussed.

PMID- 22371714
TI  - Methods of evaluation of autonomic nervous system function.
AB  - Disturbances of the autonomic nervous system play a crucial role in the
      pathogenesis and clinical course of many diseases. Recently, rapid development
      has occurred in the clinical assessment of autonomic function. Various procedures
      have been described as diagnostic tools to monitor autonomic dysfunction. Some of
      them are mostly used for research purposes. Many, however, have found their place
      in routine clinical evaluation. Our paper presents selected methods of assessment
      of the autonomic nervous system with particular emphasis on those that are useful
      in diagnosis and treatment of diseases of the cardiovascular system. We discuss
      multiple tests based on cardiovascular reflexes, methods of studying heart rate
      variability as well as direct catecholamine measurements. Moreover, we outline
      tests of sudomotor function and microneurography.

PMID- 22371715
TI  - Growth retardation and delayed puberty in children and adolescents with juvenile
      idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common joint disorder in
      developing children. Juvenile idiopathic arthritis is difficult to diagnose and
      treat. In some patients, signs and symptoms can be frustratingly inconsistent,
      contradictory or idiosyncratic. Short stature in patients with JIA is usually due
      to reduced growth in the lower extremities, and only rarely due to reduced growth
      in the spinal column. In some studies, children with JIA were found to have
      infantile body proportions. Puberty is delayed in children with JIA. In children
      with chronic arthritic disorders, there is a strong correlation between the
      activity of the disease and the age of puberty. The main goals in reducing growth
      retardation in children with JIA are promoting timely remission and reducing the
      duration and dosage of corticosteroid treatment. It is important to regularly
      monitor physical development. Further improvements to the treatment protocol
      depend on continued interdisciplinary research involving paediatricians,
      rheumatologists and clinical anthropologists.

PMID- 22371716
TI  - How effective are strategies for non-communicable disease prevention and control
      in a high risk population in a developing country? Isfahan Healthy Heart
      Programme.
AB  - INTRODUCTION: The Isfahan Healthy Heart Programme (IHHP) is a community-based
      programme for non-communicable diseases prevention and control using both a
      population and high risk approach in Iran. This study demonstrated the efficacy
      of IHHP interventional strategies to improve lifestyle behaviours in a population
      at risk for developing cardiovascular diseases. MATERIAL AND METHODS: Healthy
      Lifestyle for NCDs High Risk Population is one of ten projects of IHHP. High risk
      individuals were defined as those who have at least one risk factor for
      developing coronary artery disease (CAD). Changes of behavioural indicators have
      been compared between two areas with a survey after 5 years of intervention.
      RESULTS: Among high risk individuals in the intervention and reference areas,
      77.8% and 82.5% had at least one major risk factor for CAD. The prevalence of
      major risk factors for CAD (except cigarette smoking) was decreased in both
      intervention and reference areas during 5 years of intervention and the pattern
      of diet and physical activity was improved. CONCLUSIONS: Interventional
      activities in IHHP targeting the high risk population seem to be effective in
      improving lifestyle behaviour, increasing awareness and control of risk factors
      of the high risk population.

PMID- 22371717
TI  - Short-term results of community-based interventions for improving physical
      activity: Isfahan Healthy Heart Programme.
AB  - INTRODUCTION: To assess the effect of a comprehensive community-based programme
      for increasing physical activity (PA) after 2 years of interventions. MATERIAL
      AND METHODS: A 6-year, action-oriented, comprehensive, and integrated community
      based study, entitled the Isfahan Healthy Heart Programme, was conducted in Iran
      from the year 2000. The interventions targeted the whole population of nearly
      2,180,000 living in two cities, and were compared with another city considered as
      a reference. Educational, environmental and legislative interventions were
      conducted at the community level. Annual evaluations were performed among 6,000
      representative individuals. This paper presents the changes in PA habits after 2
      years of interventions for increasing PA. The PA habits were assessed by using
      the Baecke questionnaire, and an energy expenditure of 150 kcal for daily leisure
      time physical activity was adopted as a cut-off for defining active and inactive
      lifestyle. RESULTS: In the intervention and reference areas, respectively 85 and
      83% of the population were physically inactive. From 2000 to 2002, the daily PA
      among both genders decreased in both intervention and reference communities.
      Meanwhile, the leisure-time PA increased significantly in the intervention area,
      but decreased in the reference area. The transportation PA did not significantly
      change in the intervention area, but showed a remarkable decline in the reference
      area. CONCLUSIONS: We suggest that the synergism resulting from community
      collaborations has been effective in improving some aspects of PA in our
      community. The ongoing changes in environmental factors and policies can help in
      increasing the worksite and transportation PA in later stages of this community
      based programme.

PMID- 22371718
TI  - Prevalence of transthoracic echocardiographic abnormalities in patients with
      ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
AB  - INTRODUCTION: This study investigated the prevalence of transthoracic
      echocardiographic abnormalities in patients with ischemic stroke (IS),
      subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) in sinus
      rhythm. MATERIAL AND METHODS: The patients included 120 with IS, 30 with SAH, and
      41 with ICH. All diagnoses were confirmed by magnetic resonance imaging or brain
      computed tomography. Two-dimensional echocardiograms were taken at the time
      stroke was diagnosed. All echocardiograms were interpreted by an experienced
      echocardiographer. RESULTS: Of 120 IS patients, 1 (1%) had a left ventricular
      (LV) thrombus, 1 (1%) had mitral valve vegetations, 30 (25%) had LV hypertrophy,
      26 (22%) had abnormal LV ejection fraction, 4 (3%) had mitral valve prolapse, 33
      (28%) had mitral annular calcium (MAC), 40 (33%) had aortic valve calcium (AVC),
      3 (3%) had a bioprosthetic aortic valve, 10 (8%) had aortic stenosis (AS), 6 (5%)
      had atrial septal aneurysm, 2 (2%) had patent foramen ovale, and 40 (33%) had no
      abnormalities. Of 30 SAH patients, 5 (17%) had LV hypertrophy, 1 (3%) had
      abnormal LV ejection fraction, 1 (3%) had AS, 4 (13%) had MAC, 5 (17%) had AVC,
      and 20 (67%) had no abnormalities. Of 41 ICH patients, 9 (22%) had LVH, 1 (2%)
      had abnormal LV ejection fraction, 1 (3%) had AS, 6 (15%) had MAC, 8 (20%) had
      AVC, and 22 (54%) had no abnormalities. CONCLUSIONS: Transthoracic
      echocardiographic abnormalities are more prevalent in patients with IS than in
      patients with SAH or ICH.

PMID- 22371719
TI  - Assessment of plantar pressure and balance in patients with diabetes.
AB  - INTRODUCTION: Patients with diabetes for more than 10 years may have an increase
      in peak plantar pressure, considerable postural oscillation, balance deficit,
      alterations in gait pattern and an increased risk of falls. The aim of the
      present study was to assess the correlation between plantar pressure distribution
      and balance in patients with diabetes using a pressure platform (Footwork).
      MATERIAL AND METHODS: The study was carried out at the Human Movement Clinic of
      the Centro Universitario de Belo Horizonte (Brazil). The sample was made up of 18
      right-handed individuals with type 2 diabetes - 14 females and 4 males - with an
      average age of 58.72 +/-9.54 and an average of 18.56 +/-6.61 years since
      diagnosis. RESULT: Data analysis revealed that greater peak plantar pressure on
      the right hindfoot led to greater radial displacement (Rd) (r = 0.2022) and
      greater displacement velocity (r = 0.2240). Greater peak plantar pressure on the
      left hindfoot also led to greater displacement velocity (P) (r = 0.5728) and
      radial displacement (RD) (r = 0.1972). A positive correlation was found between
      time elapsed since diagnosis and peak midfoot pressure (r = 0.3752) on the right
      and left side as well as between BMI and plantar pressure on all regions of the
      foot. CONCLUSIONS: The data reveal a correlation between postural oscillation and
      peak plantar pressure on the hindfoot.

PMID- 22371720
TI  - The place of antibiotics in management of irritable bowel syndrome: a systematic
      review and meta-analysis.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal
      disease with an obscure pathophysiology. Current treatments for IBS have modest
      efficacy at best and the need for a robust therapy for IBS remains unmet. As
      small intestinal bacterial overgrowth has been proposed to be involved in
      pathogenesis of IBS, antibacterial agents might be efficacious in treatment of
      this condition. MATERIAL AND METHODS: PubMed, Embase, Scopus, Google Scholar, Web
      of Science, and Cochrane Central Register of Controlled Trials were searched for
      studies comparing the efficacy of antibiotics in the management of IBS and/or IBS
      type symptoms. Data were collected from 1966 to April 2009. Clinical response was
      considered as our key outcome of interest. RESULTS: Of five trials that evaluated
      the effect of antibiotics in IBS, two randomized placebo-controlled trials met
      the inclusion criteria for the meta-analysis. This meta-analysis included 234
      patients with IBS-type symptoms of whom 181 met the Rome criteria for IBS. The
      pooled relative risk (RR) for "clinical response in IBS" was 2.04 (95% confidence
      interval [CI] of 1.23-3.40, p = 0.0061). The pooled RR for "clinical response in
      IBS-type symptoms" was 2.06 (95% CI of 1.3-3.27, p = 0.002). CONCLUSIONS:
      Although antibiotics have a statistically significant effect on IBS and bloating,
      given the evidence for the presence of publication bias, methodological
      variability of the trials and lack of a precise scientific explanation for the
      role of bacterial overgrowth in the pathophysiology of IBS, use of antibiotics on
      a regular basis in IBS patients is not recommended.

PMID- 22371721
TI  - Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea - a
      placebo controlled double-blind randomized, multi-center study.
AB  - INTRODUCTION: Antibiotic associated diarrhea (AAD) is a frequently encountered
      adverse event following antibiotic administration. Evidence suggests that
      probiotics may be beneficial in preventing and decreasing the severity of AAD.
      MATERIAL AND METHODS: Adult patients who were prescribed antibiotics for 3-14
      days were enrolled from eight Canadian centers. Study treatment was randomized at
      a 1 : 1 ratio of BIO-K+CL1285( ((r)) ) or placebo and was administered within 24
      h of initiation to 5 days after termination of antibiotherapy. Patients were
      followed for 21 days after last dose of study treatment. The primary outcome was
      severity and incidence of AAD. Severity was measured by the total number of days
      with diarrhea and incidence was defined as the number of patients with at least
      one day with diarrhea over the total number of patients enrolled in the study.
      RESULTS: 216 patients were randomized to BIO-K+ and 221 to placebo. The mean (SD)
      number of days with diarrhea was 1.19. (3.20) days for the placebo and 0.67
      (2.05) days for BIO-K+CL1285( ((r)) ) (p = 0.040). Adjusted multivariate linear
      regression results showed that the duration of diarrhea for BIO-K+CL1285 ((r))vs.
      placebo was reduced by 51.5% (b[SE] = 0.515 [0.256], p = 0.045). The incidence of
      diarrhea was 21.8% for the BIO-K+ and 29.4% for the placebo group (OR = 0.667, p
      = 0.067). Multivariate logistic regression, showed that the adjusted odds ratio
      of AAD in patients receiving BIO-K+ vs. placebo was 0.627 (p = 0.037). Study
      treatment was well tolerated. CONCLUSIONS: BIO-K+ is effective for preventing and
      reducing the severity of AAD in patients receiving antibiotic therapy in a
      hospital setting.

PMID- 22371722
TI  - Preliminary results of prognostic significance of proliferating cell nuclear
      antigen expression in advanced primary larynx carcinomas and lymph node
      metastases.
AB  - INTRODUCTION: The aim of this study was to investigate the prognostic
      significance of proliferating cell nuclear antigen (PCNA) expression in laryngeal
      carcinoma in relation to clinicopathological features. Special emphasis was
      placed on examining the relationship of PCNA expression in the primary tumour and
      PCNA expression in corresponding lymph node metastases obtained from the same
      patients. MATERIAL AND METHODS: The study included 60 patients with advanced
      larynx carcinoma who had received treatment and follow-up for at least 5 years.
      Sixty laryngeal carcinoma specimens and metastatic lymph nodes from 24 patients
      were examined for immunohistochemical PCNA expression. RESULTS: The percentages
      of PCNA positive cells were significantly higher in the primary tumours which
      developed lymph node metastases than in those without metastases. The fraction of
      PCNA immunolabelled cells in metastatic lymph nodes increased significantly when
      compared with the PCNA positive cell score in their corresponding primary tumours
      obtained from the same patient. There was a significant difference in PCNA index
      score in primary tumours between the group of patients who survived a 5-year
      period and those who died within 5 years after treatment. CONCLUSIONS: Our data
      demonstrate that a high proliferation index in primary larynx tumours is retained
      and increased in corresponding lymph node metastases. Measurement of the fraction
      of cancer cells stained for PCNA in primary larynx carcinomas can be helpful in
      selecting tumours with high aggressiveness potential that are more likely to
      develop neck metastases and thereby in identifying patients who need elective
      lymph node dissection or additional treatment.

PMID- 22371723
TI  - Estimation of TGF-beta1 genotypes in Egyptian smokers; association with FEV(1) in
      COPD patients.
AB  - INTRODUCTION: TGF-beta1 is a cytokine with many different effects on cell
      proliferation, differentiation and inflammation and can protect against the
      development of COPD. This work aims to study the association between COPD and the
      TGF-beta1 gene genotypes. MATERIAL AND METHODS: The study included 70 males: 25
      smokers with COPD, 25 resistant smokers, and 20 normal non-smokers as the
      control. They were subjected to spirometry pre- and post-bronchodilator (FEV(1),
      FEV(1)/FVC), estimation of serum level of TGF-beta1 gene by PCR and RFLP.
      RESULTS: The percent of Pro-Leu was 28% in the COPD group, 84% in the resistant
      smokers group and 85% in the control group. There was a highly significant
      statistical difference in FEV(1)% of predicted associated with the distribution
      of TGF-beta1 gene genotypes: 56.9 +/-8.4% with Pro-Leu genotype and 35.5 +/-8.8%
      with Leu-Leu genotype in COPD patients, 93.2 +/-6.2% with Pro-Leu genotype and
      86.7 +/-0.9% with Leu-Leu genotype in the resistant smokers group. CONCLUSIONS:
      The Pro-allele genotype is associated with increased production of TGF-beta1,
      which has a protective role against the development of COPD and is important in
      preserving the decline of FEV(1) in COPD patients.

PMID- 22371724
TI  - Can immune parameters be used as predictors to distinguish between pulmonary
      multidrug-resistant and drug-sensitive tuberculosis?
AB  - INTRODUCTION: Despite the development and wide implementation of Directly
      Observed Therapy Strategies (DOTS), multidrug-resistant tuberculosis (MDR-TB)
      remains a serious global health threat. In this study, the role of host immune
      response in patients with MDR-TB is investigated and compared with that of
      patients with smear-positive drug-sensitive tuberculosis (SP-TB). MATERIAL AND
      METHODS: 27 patients with SP-TB, 20 patients with MDR-TB, and 20 healthy controls
      were included in the study. Immune parameters were determined by flow cytometry
      using monoclonal antibodies in order to compare the percentage values of these
      markers in the two study groups and the control group. RESULTS: The levels of
      lymphocyte subgroups in the gate of CD45(+)/CD14(-) lymphocyte: CD45(+), CD3(+),
      CD4(+), NK, CD3/HLA-DR, CD 95(+) cells were significantly lower; by contrast
      CD23(+), CD25(+), CD19(+), CD4(+)/CD8(+), HLA-DR cells were found to be lower,
      but not significantly so in patients with MDR-TB, compared to levels in patients
      in the SP-TB and control groups. Besides these findings, the levels of NKT cells
      and (gamma)delta TCR(+) cells were significantly higher in the MDR-TB than in the
      healthy control and SP-TB group. CONCLUSIONS: The lower levels of CD3/ HLA-DR,
      CD4 (+), Fas (+), and NK, and the higher level of NKT together with (gamma)delta
      T cells in patients with MDR-TB compared to those in SP-TB may indicate a
      profound immune suppression in MDR-TB patients and thereby may denote an
      accumulation in the bacterial load. Our findings may shed light on the
      pathogenesis and prognosis of MDR tuberculosis, and may point towards the use of
      flow cytometry findings as an aid to early diagnosis in MDR-TB patients.

PMID- 22371725
TI  - Haemophilia in the developing countries: the Iranian experience.
AB  - INTRODUCTION: Management of haemophilia and inherited bleeding disorders is a
      major challenge especially in developing countries, because of a shortage or
      absence of products, the cost and the infrastructural health problems.
      Development of local expertise which results in an improved outlook and reduction
      in mortality and morbidity in these countries can be helpful for advocators in
      other developing countries. However, very little information on demography and
      organizational models for haemophilia care in developing countries are available
      in the literature. Our aim is a comprehensive report of haemophilia status and
      its management in Iran. MATERIAL AND METHODS: THE MANAGEMENT CENTER OF
      TRANSPLANTATION AND SPECIAL DISEASES (MCTSD) OF THE MINISTRY OF HEALTH OF IRAN
      DECIDED TO CARRY OUT A COMPLETE REVIEW AND COMPILATION OF ALL OF THE PUBLISHED OR
      AVAILABLE DATA ABOUT PATIENTS WITH HAEMOPHILIA (PWH) IN IRAN: their health
      status, their management planning, organizations, treatment products, facilities
      and care problems during 2007. RESULTS: 6496 patients with congenital bleeding
      disorders were registered. Most of them had haemophilia A and B and von
      Willebrand disease (vWD). However, rare bleeding disorders are seen more than
      expected. Inhibitor development is 14-28%. There are different data about
      virological status of PWH. Factor products and facilities are fairly available
      with more than 1.5 units per capita of inhabitant factor consumption.
      CONCLUSIONS: A national formulary based on facilities of the country should be
      considered and followed by collaboration among the Ministry Of Health,
      universities and non-governmental organizations.

PMID- 22371726
TI  - Screening of growth hormone deficiency in short thalassaemic patients and effect
      of L-carnitine treatment.
AB  - INTRODUCTION: Evaluation of growth hormone (GH) in short thalassaemic patients
      and effect of L-carnitine therapy in those with hormone deficiency. MATERIAL AND
      METHODS: The study included 30 beta-thalassaemic patients aged 13.8 +/-1.7 years
      and 30 children with constitutional short stature as controls. Anthropometric
      measurements (basal and after 6 months), thyroid profile, insulin-like growth
      factor-1 (IGF-1) and GH provocation by 2 tests were carried out. Eight patients
      with inadequate GH response to both clonidine and ITT were given L-carnitine
      treatment for 6 months. They were re-evaluated (clinically, anthropometrically
      and in the laboratory by doing GH stimulation test) after 6 months of therapy.
      RESULTS: Twelve (40%) patients had sub-clinical hypothyroidism and 10 (33.3%) had
      growth hormone deficiency (GHD). Peak GH and growth velocity (cm and standard
      deviation score [SDS]) were significantly lower while weight (SDS) and
      weight/height SDS were significantly higher than in patients with constitutional
      short stature (p < 0.05). A significant positive correlation was found between
      height and target height (cm). Haemoglobin levels, peak GH, IGF-1 and growth
      velocity (cm & SDS) were significantly higher and the number of blood
      transfusions was significantly lower in GH deficiency patients after L-carnitine
      treatment (p < 0.05). Delta changes were higher in height (cm & SDS), estimated
      mature height and sitting height and lower in target height - height (SDS and cm)
      six months after L-carnitine treatment in beta-thalassaemic patients with GHD (p
      < 0.05). CONCLUSIONS: Growth hormone deficiency is an aetiological factor in
      thalassaemic patients with short stature. L-carnitine can promote GH secretion
      and growth.

PMID- 22371727
TI  - Left ventricular diastolic abnormalities and the impact of hepatitis C virus
      infection in multitransfused Egyptian children.
AB  - INTRODUCTION: The aim of the study was to evaluate left ventricular cardiac
      systolic and diastolic functions by echocardiography in multitransfused children
      and the possible risk of hepatitis C virus infection as an additional factor
      impairing cardiac functions in these patients. MATERIAL AND METHODS:
      Echocardiographic studies of left ventricular function in 80 multitransfused
      patients aged 3 to 15 years with no clinical evidence of heart failure were
      included in our study. Anti-hepatitis C virus antibody was present in the sera of
      25 of them. Twenty age and sex matched normal subjects were studied as a control.
      RESULTS: Results showed left ventricular systolic abnormalities in 15 cases
      (18%). Nine cases were HCV seropositive. Dilatation of left ventricle and
      impaired systolic function guided by FS (fractional shortening) was significantly
      reduced compared to normal subjects' mean FS (p<0.01). Systolic dysfunction is
      significantly observed in hepatitis C virus seropositive cases (mean FS 29+/-7.9
      vs seronegative cases 31.4+/-10 (p<0.035). Restrictive left ventricular diastolic
      abnormalities were detected in 45 patients (56.25%). Diastolic dysfunction was
      represented in prolonged isovolumic relaxation time in comparison to the control
      group (p<0.03) and higher E wave (p<0.001) also increased the ratio of early to
      late diastolic velocity (E/A ratio, 2.03+/-0.59 vs 1.6+/-0.27, p<0.05). No
      significant difference in diastolic functions was found between HCV seropositive
      and seronegative groups. There is a weak negative correlation between left
      ventricular FS and serum ferritin level (r=0.77, p<0.001). CONCLUSIONS:
      Multitransfused children are more liable to left ventricular diastolic
      dysfunction suggested by impaired relaxation probably due to iron overload and
      anaemia. Hepatitis C virus infection is an additional factor which might share in
      impairing left ventricular systolic function. Left ventricular performance is
      better preserved when chelation treatment is adjusted to maintain serum ferritin
      at <1000 ng/ml.

PMID- 22371728
TI  - Human bocavirus infections in hospitalized Greek children.
AB  - INTRODUCTION: The epidemiology of human bocavirus (HBoV) infections has not been
      described in Greece, a south-eastern European country. To define the
      epidemiological profile and the clinical characteristics associated with HBoV
      infection in a population of children hospitalized with respiratory tract
      infection. MATERIAL AND METHODS: During a one-year period throat swab samples
      were collected from 370 previously healthy children, aged 14 days to 13 years,
      admitted to two different paediatric wards because of respiratory tract
      infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene.
      RESULTS: Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases
      were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases
      were observed only during the cold months. The mean age of children was 1.8 years
      (range 2 months to 4 years). The most common symptoms were fever, cough and
      various degrees of respiratory distress. All children were clinically diagnosed
      as having lower respiratory tract infections, mainly pneumonia and acute
      laryngotracheobronchitis, and recovered uneventfully. CONCLUSIONS: HBoV
      infections occur in Greece mostly among very young children. They accounted for
      3.2% of children hospitalized with acute respiratory disease. Cases were observed
      only in late autumn to early spring.

PMID- 22371729
TI  - Bone mineral density, bone turnover markers, lean mass, and fat mass in Egyptian
      children with congenital adrenal hyperplasia.
AB  - INTRODUCTION: Aim of this paper is to assess bone mineral density (BMD) and body
      composition, by dual energy X-ray absorptiometry (DXA), and various markers of
      bone growth, in a group of children with congenital adrenal hyperplasia (CAH) on
      long-term glucocorticoid therapy. MATERIAL AND METHODS: A case-control study
      included thirty patients with CAH with different states of metabolic control.
      Their mean age was 7.5 +/-4.2 years. All patients are subjected to BMD using DXA
      at the neck of the femur and lumbar spine. A blood sample was taken for
      assessment of osteocalcin, osteoprotegerin, and procollagen type 1, as markers of
      bone formation, as well as RANKL and urinary deoxypyridinoline (DPD), as markers
      of bone resorption. RESULTS: We found no difference in BMD in patients and
      control subjects; however, patients showed significantly lower serum osteocalcin
      (p = 0.008) and osteoprotegerin (p = 0.0001) and significantly higher serum RANKL
      levels (p = 0.0001). Our results show that patients had significantly lower lean
      body mass (p = 0.005) and fat/lean ratio (p = 0.008) compared to matched
      controls. The duration of treatment showed a significant negative correlation
      with procollagen type 1 (r = -0.49, p = 0.02) and lean mass % (r = -0.43, p =
      0.04); however, it showed a significant positive correlation with total fat mass
      % (r = 0.6, p = 0.0006), and fat/lean ratio (r = 0.43, p = 0.04). Dose of steroid
      had a significant positive correlation with BMI SDS (r = 0.4, p = 0.02).
      CONCLUSIONS: Bone mineral density is normal but bone turnover is low in patients
      with CAH. There is an increase in fat/lean mass in patients with CAH.

PMID- 22371730
TI  - Indirect (chronic) self-destructiveness and modes of suicide attempts.
AB  - INTRODUCTION: Suicides and suicide attempts may be considered as manifestations
      not only of direct self-destructiveness, but also of indirect (chronic) self
      destructiveness. The aim of this work is to assess the relation between intensity
      of indirect self-destructiveness and suicide attempt modes. MATERIAL AND METHODS:
      The research was conducted among 147 persons after suicide attempts (114 women
      and 33 men) aged 14-33 years. The Polish version of the "Chronic Self
      Destructiveness Scale" by Kelley (CS-DS) in Suchanska's adaptation was used.
      RESULTS: EXAMINED PERSONS APPLIED SEVERAL MODES OF COMMITTING SUICIDE:
      pharmacological drugs, exsanguination, hanging, jumping from a height, asphyxia,
      poisoning, and throwing oneself under a moving car. The most frequent are
      pharmacological drugs (42.31%) and exsanguination (25.60%); the rarest is
      throwing oneself under a car (1.28%). Relations between indirect self
      destructiveness and the following suicide attempt modes were found:
      pharmacological drugs (0.366, p = 0.00001), poisoning (0.667, p = 0.01), and
      throwing oneself under a car (0.542, p = 0.04). There were found three clusters
      regarding the intensity of indirect self-destructiveness (low, medium and high).
      The largest differences concerned hanging, jumping from a height (medium CS-DS),
      poisoning and throwing oneself under a car (high CS-DS). There is a relation
      between indirect self-destructiveness and recurrence of suicide attempts (Kendall
      Tau = 0.217, p = 0.007); the intensity of indirect self-destructiveness
      differentiates the risk of consecutive suicide attempts (F = 2.871, p = 0.05).
      CONCLUSIONS: The implications of the findings are mainly of preventive and
      therapeutic nature. In the preventative aspect, the subject of interest should be
      not only persons with a tendency to the active form of indirect self
      destructiveness, but also persons exhibiting its passive form.

PMID- 22371731
TI  - Recurrent syncope and hypocalcaemic cardiomyopathy as manifestations of Fahr's
      syndrome.
AB  - In our report we would like to present a case of a 60-year-old patient with
      epileptic seizures, affective disturbances, only mild neurocognitive disorders
      and cardiomyopathy. A female patient was taken to the internal ward with a
      tentative diagnosis of recurrent syncope. Laboratory results disclosed severe
      hypocalcaemia, hypoparathyroidism, and hypothyroidism. An echocardiogram revealed
      left ventricle systolic dysfunction. Computed tomography revealed massive
      intracranial calcifications typical for Fahr's syndrome. Our patient demonstrated
      only mild neurological and psychiatric symptoms, but developed hypocalcaemic
      heart failure. It is possible that some cases of Fahr's syndrome remain
      undiscovered, particularly patients taken to internal wards with mild
      neurological or psychiatric signs.

PMID- 22371732
TI  - Spontaneous rupture of adrenal haemangioma mimicking abdominal aortic aneurysm
      rupture.
AB  - Serious bleeding from a ruptured adrenal mass limits preoperative diagnostics and
      can necessitate urgent laparotomy to control blood loss. A 45-year old man
      underwent an emergency laparotomy due to severe retroperitoneal haemorrhage
      causing hypovolaemia. Detailed retroperitoneal dissection after splenectomy and
      clamping of the abdominal aorta revealed bleeding from a ruptured haemangioma of
      the left adrenal gland. Following a left adrenalectomy, the patient returned to a
      stable haemodynamic state. Adrenal haemangiomas are rare, but may cause
      spontaneous life-threatening haemorrhage.

PMID- 22371733
TI  - Recurrent hypoglycaemia in a type 2 diabetes patient - diagnostic difficulties.
AB  - Hypoglycaemia is the most frequent acute complication of diabetes, regardless of
      the type of diabetes and the treatment method. Hormonally active tumours of the
      pancreas, insulinomas, which belong to digestive tract neuroendocrine tumours,
      constitute one of the less frequent causes of hypoglycaemia. This paper presents
      a case of a 60-year-old type 2 diabetes patient with recurrent hypoglycaemic
      events, in whom an insulin-secreting hepatic neuroendocrine tumour was diagnosed.
      We suggest performing a diagnostic workup taking into consideration insulinoma in
      patients with diabetes who experience frequent otherwise inexplicable
      hypoglycaemic events, particularly when they recur despite decreased dose or
      discontinuation of hypoglycaemic agents.

PMID- 22371734
TI  - Stevens Johnson syndrome after carbamazepine and SJS/TEN overlap syndrome after
      amoxicillin: case reports and a review.
AB  - We present a case of Stevens Johnson syndrome in a child after carbamazepine
      application and Stevens Johnson/TEN overlap syndrome in an adult after
      amoxicillin application. On the basis of two reported cases we review the most
      commonly associated drugs, the postulated pathogenesis, clinical manifestation
      and management in these severe life-threatening diseases. We especially discuss
      the controversial systemic corticosteroid therapy. Topical care is also
      discussed.

PMID- 22371735
TI  - First Polish Cowden syndrome patient with confirmed PTEN gene mutation.
AB  - Cowden syndrome is a rare hereditary disease. Incidence of the disease is
      conditioned by occurrence of mutations in the PTEN gene. The disease has a
      frequency of 1/120,000 newborn and it predisposes to the occurrence of hamartoma
      polyps in the gastrointestinal tract, skin tumours, as well as tumours of the
      breast, ovary and thyroid. Here we describe the case of a Polish patient
      diagnosed with Cowden syndrome with an identified mutation in the PTEN gene. The
      disease course of the patient is described and discussed along with other cases
      of carriers of substitution 68T>A in the PTEN gene.

PMID- 22371736
TI  - The trigemino-cardiac reflex: a view to the future.

PMID- 22371737
TI  - Extract from Aronia melanocarpa fruits potentiates the inhibition of platelet
      aggregation in the presence of endothelial cells.
AB  - INTRODUCTION: Some polyphenolic compounds extracted from Aronia melanocarpa
      fruits (AM) have been reported to be cardioprotective agents. In this study we
      evaluated the ability of AM extract to increase the efficacy of human umbilical
      vein endothelial cells (HUVECs) to inhibit platelet functions in vitro. MATERIAL
      AND METHODS: THIS STUDY ENCOMPASSES TWO MODELS OF MONITORING PLATELET REACTIVITY:
      optical aggregation and platelet degranulation (monitored as the surface CD62P
      expression) in PRP upon the stimulation with ADP. RESULTS: We observed that only
      at low concentrations (5 ug/ml) did AM extract significantly improve antiplatelet
      action of HUVECs towards ADP-activated platelets in the aggregation test.
      CONCLUSIONS: It is concluded that the potentiating effect of AM extract on the
      endothelial cell-mediated inhibition of platelet aggregation clearly depends on
      the used concentrations of Aronia-derived active compounds. Therefore, despite
      these encouraging preliminary outcomes on the beneficial effects of AM extract
      polyphenols, more profound dose-effect studies should certainly be considered
      before the implementation of Aronia-originating compounds in antiplatelet therapy
      and the prevention of cardiovascular diseases.

PMID- 22371738
TI  - Co-culture with Schwann cells is an effective way for adipose-derived stem cells
      neural transdifferentiation.
AB  - INTRODUCTION: Adipose-derived stem cells (ADSCs) could accomplish neural
      transdifferentiation with the presence of certain growth factors in vitro. It has
      been proved that bone marrow stromal cells (BMSCs) can realize neural
      transdifferentiation only by being co-cultured with Schwann cells (SCs), and in
      our former studies we have confirmed that ADSCs could do so too. This paper aims
      to investigate whether the neural induction efficiency of co-culture is as high
      as that of other strategies using chemicals or chemicals combined with some
      growth factors. MATERIAL AND METHODS: We isolated and multiplied ADSCs from adult
      Sprague-Dawley rats, and SCs from sciatic nerves of 1-to-2-day-old Sprague-Dawley
      rat pups, then induced ADSCs neural transdifferentiation through 2% dimethyl
      sulphoxide (DMSO) and DMSO combined with growth factors. Meanwhile we co-cultured
      ADSCs and SCs in Transwell culture dishes without intercellular contacts.
      Immunostaining and RT-PCR were adopted to investigate the neural
      transdifferentiation of ADSCs. Then we compared the expression differences for
      genes S100, nestin and GFAP of the above three protocols by real-time PCR.
      RESULTS: Both immunostaining and RT-PCR proved that ADSCs could accomplish neural
      transdifferentiation through each of the above three protocols. And real-time PCR
      further shows that the gene expression relative quantities for the above three
      genes are not statistically different between co-culture and induction through
      DMSO combined with growth factors (p > 0.05), but both of them are statistically
      different from induction only by DMSO (p < 0.05). CONCLUSIONS: Co-culturing ADSCs
      and SCs may be a simple, effective and practical way for ADSCs neural
      transdifferentiation.

PMID- 22371739
TI  - Cyclic tensile stretch modulates osteogenic differentiation of adipose-derived
      stem cells via the BMP-2 pathway.
AB  - INTRODUCTION: Mechanical forces play critical roles in the development and
      remodelling process of bone. As an alternative cell source for bone engineering,
      adipose-derived stem cells (ASCs) should be fully investigated for their
      responses to mechanical stress and the mechanisms responsible for osteogenic
      induction in response to mechanical signals. MATERIAL AND METHODS: We
      hypothesized that appropriate application of uniaxial cyclic tensile strain to
      ASCs could increase bone morphogenetic protein-2 (BMP-2) expression and improve
      osteogenesis of ASCs. To test our hypothesis, ASCs from the same flask of the
      same donor were subjected to tensile strain with different patterns in order to
      eliminate the difference of donor site and passage. After surface markers
      investigation, the osteo-induced ASCs were subjected to uniaxial cyclic tensile
      stretch with the following two loading patterns: long duration continuous pattern
      (6 h, 1 HZ, 2000 uE) and short duration consecutive pattern (17 min every day for
      10 consecutive days, 1 HZ, 2000 uE). Then osteogenic related genes were analysed
      by real-time PCR. RESULTS: The ASCs were positive for the markers STRO-1, CD90
      and CD44 and negative for CD34. Cyclic tensile strain of 6 continuous h' duration
      significantly increased gene expressions of BMP-2 and Runx2, and depressed OCN
      mRNA expression. In contrast, mechanical loading of 17 min every day did not
      significantly affect gene expression of BMP-2, Runx2, OCN or ALP. CONCLUSIONS: We
      indicate that ASCs may sense mechanical loading in a duration-dependent manner
      and cyclic tensile stretch may modulate the osteogenic differentiation of ASCs
      via the BMP-2 signalling pathway.

PMID- 22371740
TI  - Genetic variability and the risk of myocardial infarction in Poles under 45 years
      of age.
AB  - INTRODUCTION: Myocardial infarction is caused by the obstruction of an artery in
      places of atherosclerosis plaque rupture. Endothelial cells during their
      activation express chemoattractant and adhesion molecules whereas infiltrating
      inflammatory cells produce enzymes, predisposing a lesion to rupture. MATERIAL
      AND METHODS: We investigated the correlation between polymorphisms in the human
      genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N), MMP1 (1G/2G) and MMP3
      (-1612 5A/6A) and the risk of MI in young Poles under 45 years. There was no
      significant difference in the frequency of single nucleotide polymorphism (SNP)
      of the studied genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N) and MMP3
      (-1612 5A/6A) between patients with MI and controls. RESULTS: The analysis of the
      association of the 1G2G polymorphism with the risk of myocardial infarction
      indicated an odds ratio (OR) of 5.68 (95% confidence interval [95% CI] 2.60 to
      12.36). Other factors associated with myocardial infarction were: smoking (OR
      4.12; 95% CI 1.63-10.44), male sex (OR 16.02; 95% CI 5.90-43.46),
      hypercholesterolaemia (OR 2.74; 95% CI 1.29-5.83) and arterial hypertension (OR
      4.56; 95% CI 1.66-14.47). CONCLUSIONS: We found that only MMP1 1G/2G polymorphism
      is associated with myocardial infarction in the Polish population of individuals
      younger than 45 years. Clinical factors seemed to play a greater role in the
      analysed group.

PMID- 22371741
TI  - Asymmetrical dimethylarginine and severity of erectile dysfunction and their
      impact on cardiovascular events in patients with acute coronary syndrome.
AB  - INTRODUCTION: Coronary artery disease (CAD) and vascular erectile dysfunction
      (ED) are related to endothelial dysfunction. Elevated asymmetrical
      dimethylarginine (ADMA) levels and ED are common in patients with increased
      cardiovascular risk. Our aim was to investigate whether ADMA has a predictive
      role for major adverse cardiovascular events (MACE) in acute coronary syndrome
      (ACS). The secondary aim of this study was to investigate whether severity of ED
      predicts MACE in these patients. MATERIAL AND METHODS: Follow-up data were
      available for severity of ED in 71 patients with ACS. Plasma ADMA levels were
      determined by ELISA in 57 patients. Erectile dysfunction was assessed by the
      International Index of Erectile Function-6 (IIEF-6) score. Major adverse
      cardiovascular events (reinfarction, all-cause hospitalisation, stroke and all
      cause death) was evaluated after a median of 10 months. RESULTS: Severe ED had no
      significantly increased hazard ratio for cardiovascular events compared with
      mild, mild to moderate, and moderate ED (0.259 [95% CI 0.041-1.6], p = 0.147;
      0.605 [95% CI 0.095-3.8], p = 0.594; 0.980 [95% CI 0.233-4.1], p = 0.978; and
      0.473 [95% CI 0.052-1.3], p = 0.508). The patients who had ADMA levels >= 0.32
      umol/l had no significantly increased hazard ratio for cardiovascular events
      compared with patients who had ADMA levels < 0.32 umol/l (2.018 [95% CI 0.615
      6.6], p = 0.247). CONCLUSIONS: Severity of ED and ADMA did not increase the risk
      of cardiovascular events in follow-up patients with ACS in our study. Larger
      prospective studies are necessary to evaluate whether ADMA predicts
      cardiovascular events in patients with ACS.

PMID- 22371742
TI  - Perfusion assessed by real-time contrast echocardiography correlates with
      clinical and echocardiographic parameters in patients with first STEMI treated
      with PCI - 6-month follow-up.
AB  - INTRODUCTION: Angiographic flow in an epicardial artery does not define perfusion
      at a microvascular level in patients with acute myocardial infarction (AMI). The
      aim of the study was assessing microvascular reperfusion by myocardial contrast
      echocardiography (MCE) and left ventricular (LV) functional recovery by
      echocardiographic methods in patients treated with primary PTCA. MATERIAL AND
      METHODS: 100 consecutive patients with first ST-elevation AMI with single vessel
      disease treated successfully with primary PCI were enrolled. Regional contrast
      score index (RCSI), ejection fraction (EF), wall motion score index (WMSI), and
      end-systolic and end-diastolic volume (ESV, EDV) were evaluated during
      hospitalization and at 6-month follow-up. The patients were divided into 2 groups
      according to the absence (Group 1) or presence (Group 2) of perfusion defects on
      MCE. RESULTS: Group 1 had lower WMSI (p = 0.0009), higher EF than Group 2 (44.7
      and 55.9% respectively, p = 0.000067), and lower ESV (66.0 and 52.6 ml
      respectively, p = 0.003185). In Group 1 LVEF increased significantly on 6-month
      follow-up (p = 0.026), while in Group 2 it decreased (p = 0.0175). Both EDV and
      ESV were significantly lower in Group 1 (p = 0.0106 and p = 0.002882,
      respectively). There was a correlation between the presence of perfusion defects
      in the initial contrast echo and unfavourable change in ejection fraction during
      the follow-up (ANOVA for repeated measures, F[1.91] = 5.85, p = 0.0175). The
      combined clinical end-point (death and reinfarction) was significantly lower in
      patients without perfusion defect (p = 0.039). CONCLUSIONS: Myocardial contrast
      echocardiography results correlated with clinical outcome and recovery of
      systolic left ventricular function at 6-month follow-up.

PMID- 22371743
TI  - Silent meningioma - a rare cause of stroke in post-cardiopulmonary bypass
      patients.
AB  - Stroke in cardiac patients undergoing surgery is usually attributed to the use of
      cardiopulmonary bypass. In this report, we present an unusual cause of cerebral
      dysfunction: a meningioma leading to stroke, following coronary artery bypass
      grafting in a 62-year-old patient. Diagnosis and treatment options of the
      pathology are discussed with the guidance of the literature.

PMID- 22371744
TI  - Risk factor control and adherence to treatment in patients with coronary heart
      disease in the Republic of Srpska, Bosnia and Herzegovina in 2005-2006.
AB  - INTRODUCTION: European treatment guidelines in persons with known coronary heart
      disease (CHD) focus on adherence to antiplatelet therapy, beta-blockers,
      ACE/ARBs, and lipid-lowering agents, with goals for blood pressure (BP) of <
      140/90 mm Hg and LDL cholesterol of < 3.0 mmol/l. Data on adherence to these
      measures in Eastern Europe are limited. MATERIAL AND METHODS: The Third Republic
      of Srpska, Bosnia and Herzegovina, Coronary Prevention Study (ROSCOPS III) was
      conducted in 2005-2006 at 10 primary heath care centres in 601 patients (36%
      female, mean age 55 years) with CHD including acute myocardial infarction or
      ischaemia, coronary artery bypass graft, or angioplasty who were examined and
      interviewed at least 6 months after the event. We examined the proportion of
      subjects on recommended treatments and at goal for BP, LDL-C, and non-smoking.
      RESULTS: The proportion of subjects on recommended treatments included 61% for
      beta-blockers, 79% for ACE/ARBs, 63% for lipid-lowering agents and 74% for
      antiplatelet therapy. Only 30% of subjects were on all four of these treatments.
      59% of subjects had BP at goal of < 140/90 mm Hg and 33% were controlled to <
      130/80 mm Hg, 41% for LDL-C, and 88% were non-smokers. Improvements were seen in
      lipid-lowering and ACE/ARB drug use and non-smoking status from an earlier survey
      (ROSCOPS II) in 2002-2003. CONCLUSIONS: Our data show, despite improvement over
      recent years, that many persons with CHD in the Republic of Srpska, Bosnia and
      Herzegovina are neither on recommended treatments nor at target for BP and/or LDL
      C. Improved efforts targeted at both physicians and patients to address these
      issues are needed.

PMID- 22371745
TI  - Prevalence of use of advance directives, health care proxy, legal guardian, and
      living will in 512 patients hospitalized in a cardiac care unit/intensive care
      unit in 2 community hospitals.
AB  - INTRODUCTION: The prevalence of use of any advance directives was 26% in 112
      patients hospitalized in a cardiac care unit (CCU)/intensive care unit (ICU) in
      an academic medical center. MATERIAL AND METHODS: We investigated in 2 community
      hospitals the prevalence of use of advance directives (AD), health care proxy
      (HCP), legal guardian (LG), and living will (LW) in 512 patients hospitalized in
      a CCU/ ICU approached for AD and HCP. RESULTS: The use of AD was 22%, of HCP was
      19%, of LG was 16%, and of LW was 5%. CONCLUSIONS: The use of AD was 22%, of HCP
      was 19%, of LG was 16%, and of LW was 5% in patients hospitalized in a CCU/ICU.
      Educational programs on use of AD and of HCP need to be part of cardiovascular
      training programs and of cardiovascular continuing medical education.

PMID- 22371747
TI  - Characterization of low density lipoprotein receptor (LDLR) gene mutations in
      Albania.
AB  - INTRODUCTION: Familial hypercholesterolaemia (FH) is a clinical syndrome
      characterised by elevated serum total cholesterol (TCHOL) levels due to an
      increase in low-density lipoprotein (LDL) cholesterol, by tendon xanthomata and
      clinical manifestations of ischaemic heart disease in early life. Typically, it
      results from mutations in the low-density lipoprotein receptor (LDLR) gene. So
      far, more than 800 mutations have been reported for the LDLR gene and account for
      FH. The nature of LDLR gene mutations varies among different ethnicities. Until
      now no mutations of LDLR have been reported in the Albanian population. MATERIAL
      AND METHODS: We assessed the contribution of the LDLR gene mutations as causes of
      FH in an Albanian population. Fifty probands with a clinical diagnosis of FH were
      included. We analysed all the exons and the promoter of the LDLR gene by using
      restriction isotyping or direct sequencing. RESULTS: Twenty-one patients were
      heterozygous for the 1646G>A mutation (FH Genoa) in exon 11 and 9 patients were
      heterozygous for the 81T>C mutation in exon 2 of the LDLR gene. CONCLUSIONS: This
      report describes two LDLR gene mutations accounting for FH in Albania (1646G>A,
      81T>C).

PMID- 22371746
TI  - Evaluation of exercise capacity with cardiopulmonary exercise testing and BNP
      levels in adult patients with single or systemic right ventricles.
AB  - INTRODUCTION: The aim of the study was to evaluate exercise capacity using
      cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP)
      levels in patients with single or systemic right ventricles. MATERIAL AND
      METHODS: The study group included 40 patients (16 males) - 17 with transposition
      of the great arteries after Senning operation, 13 with corrected transposition of
      the great arteries and 10 with single ventricle after Fontan operation, aged 19
      55 years (mean 28.8 +/-9.5 years). The control group included 22 healthy
      individuals (10 males) aged 23-49 years (mean 30.6 +/-6.1 years). RESULTS: The
      majority of patients reported good exercise tolerance - accordingly 27 were
      classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in
      class III. Cardiopulmonary exercise test revealed significantly lower exercise
      capacity in study patients than in control subjects. In the study vs. control
      group VO(2max) was 21.7 +/-5.9 vs. 34.2 +/-7.4 ml/kg/min (p = 0.00001), maximum
      heart rate at peak exercise (HRmax) 152.5 +/-32.3 vs. 187.2 +/-15.6 bpm (p =
      0.00001), VE/VCO(2) slope 34.8 +/-7.1 vs. 25.7 +/-3.2 (p = 0.00001), forced vital
      capacity (FVC) 3.7 +/-0.9l vs. 4.6 +/-0.3 (p = 0.03), forced expiratory volume in
      1 s (FEV(1)) 3.0 +/-0.7 vs. 3.7 +/-0.9l (p = 0.0002) respectively. Serum BNP
      concentrations were higher in study patients than in control subjects; 71.8 +/
      74.4 vs. 10.7 +/-8.1 (pg/ml) respectively (p = 0.00001). No significant
      correlations between BNP levels and CpET parameters were found. CONCLUSIONS:
      Patients with a morphological right ventricle serving the systemic circulation
      and those with common ventricle physiology after Fontan operation show markedly
      reduced exercise capacity. They are also characterized by higher serum BNP
      concentrations, which do not however correlate with CpET parameters.

PMID- 22371748
TI  - Treatment with double dose of omeprazole increases beta-endorphin plasma level in
      patients with coronary artery disease.
AB  - INTRODUCTION: The proton pump inhibitor empirical trial, besides the analysis of
      symptoms, is the main method in the diagnosis of gastro-oesophageal reflux
      disease-related chest pain. beta-Endorphin acts as an endogenous analgesia
      system. The aim of the study was verify whether beta-endorphin plasma level is
      affected by omeprazole administration and influences the severity of anginal
      symptoms and outcome of the "omeprazole test" in patients with coronary artery
      disease (CAD) and chest pain of suspected non-cardiac origin. MATERIAL AND
      METHODS: Omeprazole was administered to 48 patients with CAD in a randomized,
      placebo-controlled, crossover study design. At the beginning of the study, and
      again after the 14-day omeprazole and placebo treatment, the beta-endorphin
      plasma concentration was determined. RESULTS: The level of plasma beta-endorphin
      after the administration of omeprazole was significantly greater than at the
      start of the study and following the placebo. Responders to omeprazole had an
      average lower beta-endorphin plasma concentration than subjects who failed to
      respond to this therapy. Subjects with symptoms in class III (according to the
      Canadian Cardiovascular Society classification) after omeprazole administration
      had a greater beta-endorphin plasma level than subjects in class II for anginal
      symptom severity. CONCLUSIONS: Fourteen-day therapy with a double omeprazole dose
      significantly increases the beta-endorphin plasma concentration in patients with
      CAD. Circulating beta-endorphin does not seem to be involved in the mechanism for
      the "omeprazole test" outcome, although an individually different effect on pain
      threshold cannot be excluded.

PMID- 22371749
TI  - The delivery of prevention programmes for cardiovascular disease and chronic
      obstructive pulmonary disease in Lodz by primary care physicians.
AB  - INTRODUCTION: In Poland, the National Health Fund (NHF) has contracted
      preventative interventions in primary health care (PHC) delivered by family
      physicians, internists, paediatricians and other physicians. The aim of the study
      was determining whether there is a correlation between PHC physicians'
      specialisation and the rate of interventions delivered for the prevention of
      cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD).
      MATERIAL AND METHODS: A retrospective observational study of the NHF 2005 data
      related to the delivery of prevention programmes using Spearman's rank
      correlation coefficient (rho). RESULTS: Out of 133 PHC providers in Lodz, 25
      participated in the cardiovascular disease (CVD) prevention programme, 22 in the
      chronic obstructive pulmonary disease (COPD) prevention programme at a basic
      level, and 20 at an extended level (with contract completion rates respectively
      of 55.2, 47.8 and 51.5%). When all three prevention programmes were analysed
      together, the correlation between the rate of preventative interventions by
      physicians with a particular specialisation and the contract completion rate was
      positive (rho > 0) only for family physicians. CONCLUSIONS: Participation of
      primary health care providers in preventative programmes and the rates of their
      delivery of interventions were low despite additional funding. The correlation
      between the proportion of physicians with a particular specialisation, involved
      in CVD and COPD prevention interventions delivery, and the rate of the programme
      accomplishment was the strongest for family physicians.

PMID- 22371750
TI  - Evaluation of the level of antibodies against Chlamydophila (Chlamydia)
      pneumoniae in post-surgery heart ischaemia patients and their clinical conditions
      - a six-year study.
AB  - INTRODUCTION: Inflammatory conditions modulated by Chlamydophila (Chlamydia)
      pneumoniae are considered to play an important role in the onset of
      atherosclerosis. In this paper we present the results of progressive observation
      of C. pneumoniae antibody titres in patients who underwent coronary artery bypass
      graft (CABG). MATERIAL AND METHODS: The objective of our research was a
      prospective observation of antibody titres in IgA and IgG class antibodies
      against C. pneumoniae using indirect immunofluorescence in a group of 155 post
      surgery CABG patients suffering from heart ischaemia. The microbiological test
      results were compared with patients' present coronary complaints evaluated on the
      CCS scale during a six-year period. RESULTS: Six years after CABG, 128 patients
      (82.6%) are still alive. During the study a positive serological conversion of
      antibody titres was observed in 36 patients in the IgA class antibodies, and in
      26 patients in the IgG class. The group of patients with no antibodies against C.
      pneumoniae decreased from 23.2 to 3.4%, while the group of patients with
      antibodies in both IgG and IgA classes increased from 52.3 to 83.9%. The average
      CCS degree decreased from 3.18 before CABG to 1.65 in the present study.
      CONCLUSIONS: These results show no connection between the serological symptoms of
      chronic C. pneumoniae infection and coronary complaints evaluated on the CCS
      scale during a six-year study on post-CABG patients suffering from heart
      ischaemia. The surgical treatment of heart ischaemia brought about long-term
      improvement in the coronary condition of the observed group of patients.

PMID- 22371751
TI  - Vascular endothelial growth factor in children with cyanotic and acyanotic and
      congenital heart disease.
AB  - INTRODUCTION: Vascular endothelial growth factor is a potent stimulator of
      angiogenesis. Children with cyanotic congenital heart disease often experience
      the development of widespread formation of collateral blood vessels, which may
      represent a form of abnormal angiogenesis resulting in increased morbidity and
      mortality. We undertook the present study to determine whether children with
      cyanotic congenital heart disease have elevated serum levels of vascular
      endothelial growth factor compared to children with acyanotic heart disease.
      MATERIAL AND METHODS: Serum was obtained from 35 children with cyanotic
      congenital heart disease and 30 children with acyanotic heart disease. Vascular
      endothelial growth factor levels were measured in the serum of these patients by
      sandwich enzyme immunoassay. RESULTS: Vascular endothelial growth factor was
      significantly elevated in children with cyanotic congenital heart disease
      compared to children with acyanotic heart disease (150.3 +/-48.1 vs. 85.4 +/-18.7
      pg/ml, respectively, p < 0.001). In the cyanotic group, oxygen saturation
      (SaO(2)) was negatively correlated with VEGF (r=-0.631, p < 0.001) while
      haemoglobin was positively correlated (r=0.781, p = 0.007). No significant
      correlations were found in the acyanotic group. CONCLUSIONS: Children with
      cyanotic congenital heart disease have elevated systemic levels of vascular
      endothelial growth factor directly related to the degree of cyanosis (SaO(2) and
      haemoglobin levels). These findings suggest that the widespread formation of
      collateral vessels in these children may be mediated by vascular endothelial
      growth factor.

PMID- 22371752
TI  - Screening for coeliac disease among Egyptian children.
AB  - INTRODUCTION: To screen for coeliac disease in Egyptian children with non
      endocrinal short stature, refractory iron deficiency anaemia and type 1 diabetes.
      Also, to evaluate the sensitivity and specificity of different serological tests
      for diagnosis of coeliac disease (CD). MATERIAL AND METHODS: The study included
      292 patients with clinical risk of CD. Testing for coeliac antibodies was
      performed, together with upper gastrointestinal endoscopy and small intestinal
      biopsy. RESULTS: Eleven patients (44%) among 25 patients with refractory iron
      deficiency anaemia, 23 patients (34.3%) among 67 patients with non-endocrinal
      short stature, and 6 patients (3%) among 200 patients with type I diabetes
      mellitus were diagnosed by jejunal biopsy as having coeliac disease. AGA (IgG)
      had the highest sensitivity for diagnosing CD (80.0%) followed by the TTG (72.7%)
      antibody, while ARA had the highest specificity (95.9%) followed by anti-EMA
      (94.7%). CONCLUSIONS: Coeliac disease is more common in Egyptian children with
      refractory iron deficiency anaemia, non-endocrinal short stature and type 1
      diabetes than was previously thought; therefore it is mandatory to screen such
      patients for CD. Serological tests showed fairly good sensitivity and specificity
      for the diagnosis; however, intestinal biopsy remains the cornerstone for
      definitive diagnosis of patients with immunological reaction to gluten.

PMID- 22371753
TI  - A meta-analysis on the efficacy and tolerability of natalizumab in relapsing
      multiple sclerosis.
AB  - INTRODUCTION: Natalizumab is a new humanized monoclonal antibody used in multiple
      sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and
      tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and
      Cochrane Central Register of Controlled Trials were searched for studies that
      investigated the efficacy and/or tolerability of natalizumab in MS. Data were
      collected from 1966 to 2008 (up to October). MATERIAL AND METHODS: THE SEARCH
      TERMS WERE: "multiple sclerosis" or "MS" and "natalizumab". "Mean change in
      Expanded Disability Status Scale (EDSS)", "number of patients with at least one
      relapse", and "number of patients with at least one new gadolinium (Gd)-enhancing
      lesion" were the key outcomes of interest for assessment of efficacy. "Any
      adverse events", "serious adverse events", "death", and "withdrawal because of
      adverse events" were the key outcomes for tolerability. Among existing trials,
      four randomized placebo controlled clinical trials met our criteria and were
      included. RESULTS: Pooled relative risk for at least one relapse in four trials
      including all doses was 0.7, with a non-significant RR (95% CI: 0.42-1.17, p = 0.
      17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg
      or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa
      significant RR (95% CI: 0.42-0.61, p < 0.0001). The summary RR for at least one
      new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05-1.01, p =
      0.051). Three deaths were reported in the natalizumab group. Comparing adverse
      events between natalizumab and placebo yielded a non-significant RR of 0.99 (95%
      CI: 0.96-1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of
      0.39 (95% CI: 0.29-0.52, p < 0.0001) for serious adverse events (n = 2). The
      summary RR for withdrawal due to adverse events by natalizumab vs. placebo
      therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68-3.02, p =
      0.35). CONCLUSIONS: It seems that using 3 or 6 mg/kg every 4 weeks is the best
      method of administration of natalizumab for preventing relapse and occurrence of
      new Gd-enhancing lesions. The current data on the efficacy and safety of
      natalizumab are insufficient to reach a convincing conclusion and thus further
      clinical trials are still needed.

PMID- 22371754
TI  - Serum proteomic profile analysis for endometrial carcinoma detection with MALDI
      TOF MS.
AB  - INTRODUCTION: Endometrial carcinoma is the one of the leading causes of terminal
      cancer death in women, and the best way to solve it is through an early
      diagnosis. Serum proteomic profiling is a promising approach to classify disease
      versus normal and matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF). This analysis is a new potential tool for the diagnosis
      of human diseases. The objective of our study was to assess the feasibility of
      mass spectrometry, based on serum proteomic pattern for the discrimination of
      endometrial carcinoma patients from healthy control patients. MATERIAL AND
      METHODS: By using 30 pre-operative endometrial carcinoma serum samples and 30
      healthy controls, we generated MALDI-TOF protein profiles, established the serum
      detection model, and analyzed the data. Furthermore, we validated the data and
      got the total sensitivity (97.6%) and specificity (100%), which could classify
      all the samples well and demonstrated the high, significant separation ability.
      RESULTS: Our results indicated that high sensitivity and specificity classify
      endometrial carcinoma by the serum detection model and showed the potential
      usefulness of serum protein profiles. CONCLUSIONS: From these results, we could
      tell that MALDI-TOF MS is a potential tool for diagnosing diseases by the use of
      serum samples and will be widely used in the future for clinical work.

PMID- 22371755
TI  - Characteristics of obstetric fistulas and the need for a prognostic
      classification system.
AB  - INTRODUCTION: To evaluate the need for a prognostic classification system for
      obstetric fistula (OF) with the data obtained by a voluntarily action for OF
      repair in a regional hospital and Niger, Africa. MATERIAL AND METHODS: Obstetric
      fistula (OF) characteristics of 51 women with vesicovaginal fistula in a fistula
      campaign in Maradi Regional Hospital, Niger were evaluated. Initial basic
      gynecological examination, methylene blue (MBT) test and direct cystoscopy were
      used to describe the characteristics of the lesions. Demographic and clinical
      data were compared with the existing literature. RESULTS: In 31 (60%) cases were
      the sizes of the fistula greater than 4 cm. The urethra was circumferentially
      lost in 8 (15.7%) women. In 18 (35.3%) women the trigone was involved. Extensive
      fibrosis was present in 10 (19.6%) patients. Only in 11 (21.6%) patients without
      any obliterating scarring, neither the trigone nor urethra were damaged. Five
      (9.8%) patients had severe infection. Five (9.8%) had multiple lesions. Thirty
      four (66.6%) had a history of at least one previous attempt for fistula repair. A
      significant proportion of women were divorced or abandoned from their husband,
      and socially isolated. CONCLUSIONS: A simple, reproducible and universally
      accepted scientific classification or staging system for OF dealing with outcomes
      rather than anatomic landmarks should replace the present proposed classification
      systems for prognostic and ethical purposes.

PMID- 22371756
TI  - Vasopressor choice for hypotension in elective Cesarean section: ephedrine or
      phenylephrine?
AB  - INTRODUCTION: Hypotensive episodes are a common complication of spinal anesthesia
      during Cesarean section. The purpose of this study was to compare the
      effectiveness and the side effects of vasopressors, ephedrine and phenylephrine,
      administered for hypotension during elective Cesarean section under spinal
      anesthesia. MATERIAL AND METHODS: The study consisted of 100 selected ASA I/II
      females scheduled for elective Cesarean section under spinal anesthesia. Each
      patient was randomly assigned to one of the two double-blind study groups. Group
      E received 1 ml ephedrine (5 mg/ml) with normal saline if hypotension was present
      (n=50). Group P received 1 ml phenylephrine (100 ug/ml) with normal saline if
      hypotension developed (n=50). Heart rate (HR), systolic blood pressure (SBP),
      diastolic blood pressure (DBP), mean arterial pressure (MAP) were compared within
      and between groups to basal levels at time increments of 0, 2, 4, 6, 8, 10, 15,
      20, 25, 30, 45, and 60 min from start of surgery. Incidence of side effects and
      neonatal outcomes were studied between groups. RESULTS: All patients required
      vasopressor therapy for hypotension. Administration of phenylephrine was
      associated with significant drop in HR. Changes in SBP, DBP, and MAP were similar
      in both groups for most observed times. The incidences of nausea/vomiting and
      tachycardia were significantly higher in the ephedrine group. CONCLUSIONS:
      Phenylephrine and ephedrine are acceptable choices to combat maternal hypotension
      related to spinal anesthesia in elective Cesarean section. Complications of intra
      operative nausea and vomiting, tachycardia and bradycardia should be considered
      when choosing a vasopressor, suggesting phenylephrine may be more appropriate
      when considering maternal well-being.

PMID- 22371757
TI  - Do soluble p55 and p75 TNF-alpha receptor concentrations play a role in women
      with primary sterility?
AB  - INTRODUCTION: In modern medicine the cause of infertility is believed to be
      immune mechanism disorders as well as immune over-reactivity. The objective of
      this thesis is to evaluate the diagnostic usefulness of measuring the
      concentration of soluble TNF-alpha receptors p55 and p75 in women with primary
      infertility. MATERIAL AND METHODS: EXAMINATION SUBJECTS: 41 female patients with
      primary sterility in the period January-September 2005. The control group
      consisted of 13 female patients. For identification of soluble receptors' p55 and
      p75 TNF-alpha concentration was used commercial ELISA kits. Quantitative in vitro
      method of hormone identification in blood serum of plasma (ECLIA) has been used
      to estimate hormone concentration. Results have been analyzed with Student's t
      test, Wilcoxon's test, Fisher's exact test and Spearman's test. P value<0.05 was
      considered significant. RESULTS: There is no significant statistical relation
      between concentration of soluble p55 and p75 TNF-alpha receptors and age, BMI
      index, or length of periods. In the case of soluble p75 TNF-alpha receptor a
      statistical correlation with length of period was found (p = 0.004). From the
      statistical point of view, the most advantageous relation was found in the case
      of p75 TNF-alpha soluble receptor and thickness of endometrium (p = 0.007) as
      well as the correlation of p55/p75 soluble receptors (p = 0.05). The statistical
      analysis of correlations between TNFR1 and TNFR2 receptors and concentration of
      hormones FSH, LH, PRL, E2 and testosterone showed no dependence of TNFR1 and
      TNFR2 receptor concentrations and concentrations of examined hormones.
      Statistical analysis of relations of TNFR1/TNFR2 receptor concentrations revealed
      a significant correlation between these receptors and concentration of LH (p =
      0.05). CONCLUSIONS: The correlation between endometrium thickness, size of
      dominating vesicle and concentration of LH compared to concentrations of soluble
      TNF-alpha?receptors p55 and p75 and their ratio might condition the time of
      survival of the vesicle or lead to excessive expression of its atresion-leading
      conditions.

PMID- 22371758
TI  - Risk factors in Central Poland for the development of superficial and nodular
      basal cell carcinomas.
AB  - INTRODUCTION: In the last decades the number of skin carcinomas has dramatically
      increased, which is mainly connected with changes in lifestyle, especially with
      common use of artificial light sources such as sunbeds. Basal cell carcinoma
      (BCC) is the most common form of skin cancer in white populations. Basal cell
      carcinomas are divided into subtypes, depending on their clinical picture and
      histology. The main groups are nodular (nBCC) and superficial (sBCC) ones. The
      major recognized risk factors for basal cell carcinoma (BCC) are exposure to
      chronic and intermittent burning doses of sunlight. Other risk factors leading to
      the development of the nBCC and sBCC subtypes of BCC are not well established.
      MATERIAL AND METHODS: An analysis of 123 patients with either nBCC or sBCC,
      living in Lodz, Poland, regarding various intrinsic and environmental parameters
      was undertaken following the histological diagnosis of BCC. RESULTS: No
      statistical differences were observed between the BCC subtype and sex, age, hair
      colour, eye colour, smoking, family history of skin cancer, occupation, or past
      episodes of sunburn. While sBCCs tended to occur on unexposed body sites in
      phototype I/II subjects who mainly avoided direct sunlight, nBCCs tended to occur
      on sun-exposed body sites in phototype III subjects who were frequently in direct
      sunlight. CONCLUSIONS: Thus the development of particular BCC subtypes is
      partially dependent on phototype and personal sun behaviour.

PMID- 22371759
TI  - Epidural haematoma after epidural catheter removal under multiple anticoagulant
      therapy: report of two cases.
AB  - We report two cases of epidural haematoma that probably developed after removal
      of the epidural catheter in patients receiving multiple anticoagulant and
      antiplatelet therapy. The first case is a 77-year-old male patient who underwent
      femoropopliteal artery bypass grafting surgery. The second case is a 77-year-old
      woman who underwent a semi-total replacement of the right hip, three days after
      she had a subtrochanteric fracture. Emergency laminectomy was performed in both
      patients but none experienced a full recovery.

PMID- 22371760
TI  - Colorectal cancer in the course of familial adenomatous polyposis syndrome ("de
      novo" pathogenic mutation of APC gene): case report, review of the literature and
      genetic commentary.
AB  - Colorectal cancer (CRC) is one of the most common malignant tumours in Poland.
      Annually approximately 11 000 new cases of CRC are diagnosed, while the number of
      deaths caused by CRC approaches 8 000. Five-year survival does not exceed 20%.
      Familial adenomatous polyposis (FAP) is responsible for about 1% of new cases of
      CRC. The risk of CRC in FAP syndrome is 100%, and the average age of CRC
      development is 39 years. Early colectomy is the most effective method of CRC
      prevention. We report an atypical case of CRC in a patient with FAP caused by
      2797-2800delAACA mutation of the APC gene.

PMID- 22371761
TI  - Simultaneous human herpesvirus 6-associated encephalitis and Guillain-Barre
      syndrome in a patient after matched unrelated donor haematopoietic stem cell
      transplantation.
AB  - Viral infections are still a serious diagnostic and therapeutic problem in
      patients undergoing alternative donor transplants. beta-Herpesviruses (especially
      human herpesvirus type 5, 6 and 7) are recognized pathogens in this group of
      patients and may cause central nervous system disease. Guillain-Barre syndrome
      (GBS) is a very rare complication among stem cell transplant recipients and
      usually has been attributed to infection. We report a case of resolving
      simultaneous GBS and HHV-6-associated encephalitis in a haematopoietic stem cell
      transplant recipient with preceding reactivation of cytomegalovirus (CMV)
      infection. According to our knowledge this well-documented case is probably the
      first report from Poland.

PMID- 22371762
TI  - Catechol-O-methyltransferase: potential relationship to idiopathic hypertension.
AB  - Catecholamine signaling pathways in the peripheral and central nervous systems
      (PNS, CNS, respectively) utilize catechol-O-methyltransferase (COMT) as a major
      regulatory enzyme responsible for deactivation of dopamine (DA), norepinephrine
      (NE) and epinephrine (E). Accordingly, homeostasis of COMT gene expression is
      hypothesized to be functionally linked to regulation of autonomic control of
      normotensive vascular events. Recently, we demonstrated that morphine
      administration in vitro resulted in decreased cellular concentrations of COMT
      encoding mRNA levels, as compared to control values. In contrast, cells treated
      with E up regulated their COMT gene expression. In sum, these observations
      indicate a potential reciprocal linkage between end product inhibition of COMT
      gene expression by E and morphine. Interestingly, the observed effects of
      administered E on COMT gene expression suggest an enhancement of its own
      catabolism or, reciprocally, a stimulation morphine biosynthesis.

PMID- 22371763
TI  - Indication for percutaneous aortic valve implantation.
AB  - The incidence of valvular aortic stenosis has increased over the past decades due
      to improved life expectancy. Surgical aortic valve replacement is currently the
      only treatment option for severe symptomatic aortic stenosis that has been shown
      to improve survival. However, up to one third of patients who require lifesaving
      surgical aortic valve replacement are denied surgery due to high comorbidities
      resulting in a higher operative mortality rate. In the past such patients could
      only be treated with medical therapy or percutaneous aortic valvuloplasty,
      neither of which has been shown to improve mortality. With advances in
      interventional cardiology, transcatheter methods have been developed for aortic
      valve replacement with the goal of offering a therapeutic solution for patients
      who are unfit for surgical therapy. Currently there are two catheter-based
      treatment systems in clinical application (the Edwards SAPIEN aortic valve and
      the CoreValve ReValving System), utilizing either a balloon-expandable or a self
      expanding stent platform, respectively.

PMID- 22371764
TI  - Intra-arterial versus intra-venous thrombolysis within and after the first 3
      hours of stroke onset.
AB  - The NINDS trial demonstrated for the first time the effectiveness of intravenous
      thrombolysis in improving outcome after acute ischemic stroke. The absolute
      benefit of this intervention was 11-13% greater chance of being normal or near
      normal (MRS <= 1) at 3 months. However, if patients with severe stroke were
      considered (NIHSS >= 20), the absolute benefit dropped to 5-6%, indicating that
      IV thrombolysis may not be as effective for large vessel occlusion. This
      observation was further supported by TCD studies that clearly demonstrated that
      large artery occlusions had a recanalization rate of 13-18% with IV rt-PA. Intra
      arterial thrombolysis achieves recanalization rates of 60-70%. Since tissue
      viability is clearly important, it is time to stop defining rigid time windows
      and if there is a large penumbra (20-50%) and the occlusion is in a large artery,
      there exists a logic and a growing evidence to consider either bridge therapy or
      direct intra-arterial therapy.

PMID- 22371765
TI  - Chronic alcohol exposure increases ganglia endogenous morphine levels.
AB  - INTRODUCTION: We have previously demonstrated that alcohol has the ability to
      release low levels of endogenously expressed, chemically authentic, morphine from
      neural tissues. MATERIAL AND METHODS: Presently, we demonstrate that chronic
      exposure of Mytilus edulis pedal ganglia tissues maintained in organotypic
      culture to very concentrations of 1 mM and 10 mM ethanol induces a time dependent
      increase in both endogenous morphine and dopamine (DA) levels. RESULTS: Chronic
      incubation of M. edulis pedal ganglia with 3 concentrations of DA resulted in
      statistically significant elevations of cellular morphine levels, thereby
      confirming previous studies from our laboratory establishing DA as an essential
      precursor in the morphine biosynthetic pathway. CONCLUSIONS: By understanding
      multiple debilitating effects of alcohol on "morphinergic" signaling, we may
      understand the ravages of neural processes associated with alcohol abuse and how
      its treatment may be made more effective.

PMID- 22371766
TI  - Environmental toxin 4-nonylphenol and autoimmune diseases: using DNA microarray
      to examine genetic markers of cytokine expression.
AB  - INTRODUCTION: Adverse progression of autoimmune diseases is linked to the
      dysregulation of cytokines. In this regard we investigated the role of 4
      nonylphenol (4-NP), as a potential contributing factor in the development of
      immune diseases and compared it to estrogens actions since 4-NP may work via
      estrogen processes. MATERIAL AND METHODS: The study made cytokine level
      expression changes in U937 cells by microarray technology coupled to RT PCR as a
      validating technique. RESULTS: It was determined that 4-NP significantly up
      regulated proinflammatory cytokine expression (toll-like-receptor [TLR]-6, TLR
      10, interleukin [IL]-1, IL-5, IL-6, IL-17C, IL-23A, IL-8RB, IL-receptor
      associated-kinase [IRAK-2], tumor-necrosis-factor-receptor [TNFR]-5, and TNFR
      10). Estrogen caused insignificant increases but the changes parralelled that of
      4-NP. Simultaneously, 4-NP down-regulated the expression of anti-inflammatory
      cytokines (IL-4 and IL-10), while estrogen up-regulated them. CONCLUSIONS: 4
      Nonylphenol may initiate its toxic effects and pose a risk to autoimmunity-prone
      individuals by eliciting effects up to 4 times more potent than estrogen.
      Overall, exposure to 4-NP may contribute to autoimmune susceptibility and/or
      exacerbate existing autoimmune conditions by dys-regulating normal expression of
      cytokines.

PMID- 22371767
TI  - Myocardial performance index after surgical correction of ventricular septal
      defects.
AB  - INTRODUCTION: The myocardial performance index (MPI) has been described as a non
      invasive Doppler measurement of ventricular function. The aim of this study was
      to assess MPI following surgical correction of ventricular septal defect (VSD)
      and to evaluate its impact on postoperative recovery. MATERIAL AND METHODS: This
      is a prospective study involving 30 children (16 girls and 14 boys) operated on
      for VSD (group I). The control group (group II) consisted of 30 healthy children
      (age and sex matched). RESULTS: We found that both the right and left ventricular
      (RV and LV) MPI correlated significantly with the ejection fraction (EF) (r = 
      0.49, p = 0.006, r = -0.51, p = 0.004, respectively). The LV EF and the LV FS
      were negatively correlated, while the left and right ventricular MPI was
      positively correlated with the: LVEDD (p = 0.000), the VSD size (p = 0.000), and
      the postoperative course of the patients in terms of the duration of ventilation
      (p = 0.000), the duration of use of inotropics (p = 0.000) and the duration of
      staying in the ICU (p = 0.000). By linear regression, the factors that correlated
      with the postoperative course of VSD surgery were the RV MPI pre-surgery, MPI 2
      days after surgery and the ejection fraction (p = 0.000). CONCLUSIONS: Myocardial
      performance index is a useful index for measurement of the left and right
      ventricular function. It correlates significantly with the ejection fraction,
      fractional shortening, VSD size, and the left ventricular size. It also
      significantly predicts the outcome of VSD surgery.

PMID- 22371768
TI  - A case series: Egyptian experience in using chemical pleurodesis as an
      alternative management in refractory hepatic hydrothorax.
AB  - INTRODUCTION: Chemical pleurodesis is an effective treatment for malignant
      effusion and pneumothorax. Although this mode of therapy is less widely accepted
      in treatment of patients with hepatic hydrothorax, the need for palliative
      treatment in such patients encouraged us to do this work. The aim of study was
      analysing the outcome of chemical pleurodesis using bovoiodine, Vibramycin and
      talc slurry in treatment of hepatic hydrothorax. MATERIAL AND METHODS: A case
      series randomized study including 23 patients with symptomatic right side hepatic
      hydrothorax not responding to medical treatment and repeated thoracocentesis was
      conducted. From March 2007 to March 2008, 19 men and 4 women with a mean age of
      54.3 +/-8.1 years (range 42-70 years) underwent medical thoracoscopies to achieve
      pleurodesis by application of 3 sclerosing agents. RESULTS: Out of the 23
      patients pleurodesis was repeated in 20 cases. Three cases did not attend their
      follow-up so their responses to pleurodesis are not known. The follow-up period
      of the study was 3 months. The procedure was effective in 15 of 20 patients
      (75%): 7/8 cases treated with bovoiodine (87.5%), and 4/6 cases with Vibramycin
      and talc slurry (66.7%) for each. There were 4 recurrences (20%) and a single
      case of mortality (5%) due to hepatic coma which can be attributed to the course
      of the disease. We detected minimal morbidity during the follow-up period of 3
      months. CONCLUSIONS: The procedure appears to be indicated for these fragile
      patients especially when medical therapy fails. Chemical pleurodesis deserves to
      be considered as an alterative therapy in such patients.

PMID- 22371769
TI  - Buerger's disease as an indicator of socioeconomic development in different
      societies, a cross-sectional descriptive study in the North-East of Iran.
AB  - INTRODUCTION: Nowadays, Buerger's disease (BD) is more common in the developing
      countries of Asia. Although its prevalence is going to decrease in the developed
      countries, its decline rate is not in parallel with that for smoking in these
      countries. Since the number of BD patients reported to MVasRc is increasing
      annually and its pathogenesis is unknown, the aim of the study was to investigate
      the smoking habits and socioeconomic status of the patients corresponding with
      Shionoya's criteria. MATERIAL AND METHODS: Poverty line was the key factor of
      economic condition. Hygiene, education, professional occupation, long-term
      unemployment and healthy work were considered as social indices. Patients under
      the poverty line in addition to weakness in more than two social indices were
      included in low socioeconomic classification. RESULTS: From the total of 86
      patients who reported to MVasRc during the 22-month study period, 71.6% and > 95%
      were new cases of BD and in low socioeconomic status respectively. Smoking ranged
      from 2 to 80 cigarettes/day. The duration of smoking before the onset of BD
      varied from 2 months to 35 years. CONCLUSIONS: There is a lack of correspondence
      between BD and decline in the prevalence of smoking in developed countries. Also,
      duration and smoking habit varied in the studied patients. On the other hand, the
      strong dependence of BD on low socioeconomic conditions, as revealed in this
      research, implies that socioeconomic status may be a risk factor for initiation
      of BD. Moreover, the prevalence of BD might be an indicator of socioeconomic
      development in different societies.

PMID- 22371770
TI  - Relationship between codon 249 mutation in exon 7 of p53 gene and diagnosis of
      hepatocellular carcinoma.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common
      malignancies worldwide. Multiple genetic and epigenetic changes are involved in
      the molecular pathogenesis of HCC. Heat shock proteins have essential roles in
      protecting cells from the potentially lethal effects of stress. Among them, HSP70
      are often overexpressed in cells of various cancers and have been suggested to
      contribute to tumourigenesis. p53 mutations in codon 249 have also been
      identified in HCC. MATERIAL AND METHODS: Fifty patients with liver disease were
      enrolled in this study compared to 10 healthy volunteers. The studied patients
      were divided into 2 groups: group I includes those suffering from HCC, group II
      includes those suffering from post-hepatitis B and C liver cirrhosis. The
      presence of p53 gene mutation was detected by DNA extraction from whole blood of
      patients and controls followed by polymerase chain reaction then restriction
      fragment length polymorphism (RFLP) analysis of codon 249 of exon 7. We also
      studied the genotypes of the HSP70 gene by PCR followed by RFLP analysis.
      RESULTS: Our results revealed no statistical difference between group I, group
      II, and the control group as regards exon 7 mutation of the p53 gene. Also the
      frequency of polymorphic genotypes of HSP70 showed no significant difference
      between the 3 studied groups. CONCLUSIONS: The present study supports the view
      that the incidence of point mutation of p53 codon 249 mutations in exon 7 of the
      p53 gene may not play a role in carcinogenesis of HCC in Egyptian patients. Also,
      genetic polymorphism in HSP70 was not associated with high risk of future
      development of HCC.

PMID- 22371771
TI  - Value of alpha-smooth muscle actin and glial fibrillary acidic protein in
      predicting early hepatic fibrosis in chronic hepatitis C virus infection.
AB  - INTRODUCTION: alpha-Smooth muscle actin (alpha-SMA)-positive hepatic stellate
      cells (HSCs) are pericytes responsible for fibrosis in chronic liver injury. The
      glial fibrillary acidic protein (GFAP), commonly expressed by astrocytes in the
      central nervous system, is expressed in vivo in the liver in a subpopulation of
      quiescent stellate cells. The reports concerning GFAP expression in human liver
      are still conflicting. The aim of the study is investigation the utility of GFAP
      compared to alpha-SMA as an indicator of early activated HSCs, in predicting
      fibrosis in chronic hepatitis C (CHC) patients. MATERIAL AND METHODS: With
      immunohistochemistry and a semi-quantitative scoring system, the expressions of
      alpha-SMA and GFAP on HSCs in liver biopsies from patients with pure CHC (n =
      34), hepatitis C virus-induced cirrhosis (n = 24), mixed CHC/schistosomiasis (n =
      11) and normal controls (n = 10) were analysed. RESULTS: The immunoreactivity of
      alpha-SMA and GFAP in perisinusoidal, periportal and pericentral areas was
      assessed. alpha-Smooth muscle actin and GFAP-positive HSCs were significantly
      increased in all diseased groups compared with normal controls. In pure CHC with
      or without cirrhosis, perisinusoidal alpha-SMA-positive HSCs were predominant in
      relation to GFAP-positive cells. On the other hand, GFAP-positive cells were
      predominant in the group of schistosomiasis as compared with the other diseased
      groups. It was noticed that expression of GFAP on perisinusoidal HSCs in CHC
      patients sequentially decreased with the progression of fibrosis. CONCLUSIONS:
      Glial fibrillary acidic protein could represent a more useful marker than alpha
      SMA of early activation of HSCs in CHC patients and seems to be an early
      indicator of hepatic fibrogenesis.

PMID- 22371772
TI  - Antiviral activity of borage (Echium amoenum).
AB  - INTRODUCTION: Borage (Echium amoenum) is a large annual plant of the Boraginaceae
      family that grows in most parts of Europe and in northern parts of Iran. The
      flower of borage is used as a medicinal herb in various countries as an
      antifebrile and antidepressant, for treatment of stress, circulatory heart
      diseases and pulmonary complaints, as a poultice for inflammatory swellings, as a
      diuretic, laxative, emollient and demulcent, and recently as a possible cancer
      protective factor. The Iranian borage is used in traditional medicine for
      infectious diseases and influenza and as an antifebrile. In this report, an
      aqueous extract of dried borage (Echium amoenum) flowers was tested in vitro for
      its antiviral activity. MATERIAL AND METHODS: Bacteriophage 3C and its specific
      host, Staphylococcus aureus 8327 were used Aqueous extract of E. amoenum dried
      flower was prepared and anti-viral activity was determined by agar overlay method
      and the burst size was determined by one-step growth experiment. Antibacterial
      activity was determined by disc diffusion, agar-well diffusion and minimum
      inhibitory concentration methods. RESULTS: The extract showed concentration
      dependent antiviral activity against free bacteriophage 3C and reduced the yield
      of phage from the host Staphylococcus aureus 8327. Antiviral activity of the
      extract is heat resistant. Autoclaving the extract at 110 degrees C for 1 h did
      not eliminate its antiviral activity and the effect was similar to the extract
      that was filter sterilized. However, the activity of the freeze-dried extract was
      diminished during 90 days of storage at 4 degrees C and the activity of the
      working solution was diminished in a one-week period at 4 degrees C. CONCLUSIONS:
      These results may provide a justification for the traditional use of the Iranian
      borage flower for infectious diseases and antifebrile activity.

PMID- 22371773
TI  - Determining entropy values equivalent to the bispectral index values during
      sevoflurane anaesthesia.
AB  - INTRODUCTION: We aimed to identify the entropy levels that would be equivalent to
      the bispectral index (BIS) levels in sevoflurane anaesthesia in patients who are
      to undergo elective lumbar disc surgery. MATERIAL AND METHODS: Thirty cases in
      ASA groups I-II who underwent lumbar disc surgery under general anaesthesia were
      included in our study after obtaining the consent of the patients and Ethics
      Committee of our medical school between January 1, 2005 and October 30, 2006. BIS
      and entropy electrodes were applied at the same time in 30 cases in the study
      group. The depth of the anaesthesia was regulated so that 10 min after beginning
      the general anaesthesia the BIS values were between 40 and 60. At the same time
      equivalent entropy values corresponding to BIS values were obtained. RESULTS: At
      the end of the study, entropy values corresponding to general anaesthesia BIS
      values were identified. General anaesthesia BIS and RE/SE values at 10 min were
      lower than the values of the control, which was statistically significant (p <
      0.05). Equivalent entropy values were obtained lower than the BIS values during
      general anaesthesia and these values were found to be statistically significant
      (p < 0.05). The blood pressure (BP) values obtained were very low at equivalent
      BIS values and when these BP values were compared with the initial BP values they
      were found to be statistically significant (p < 0.05). CONCLUSIONS: Based on this
      observation, we think that general anaesthetic agents that might cause severe
      hypotension could be more safely administered under entropy monitoring.

PMID- 22371774
TI  - Intraocular matrix metalloproteinase 2 and 9 in patients with diabetes mellitus
      with and without diabetic retinopathy.
AB  - INTRODUCTION: We aimed to investigate activities of metalloproteinases 2 (MMP-2)
      and MMP-9 in aqueous humour of patients with diabetes mellitus with various
      stages of diabetic retinopathy. MATERIAL AND METHODS: We included 36 samples of
      aqueous humour of patients suffering from diabetes mellitus, undergoing routine
      cataract surgery. Seven of them suffered from proliferative diabetic retinopathy
      (PDR), 3 had diabetic maculopathy and the remaining 26 had background or minimal
      background retinopathy only. Metalloproteinases 2 and MMP-9 activities in aqueous
      humour were measured by gelatin zymography combined with the densitometric
      imaging system. Total protein content in aqueous humour samples was also
      assessed. RESULTS: Metalloproteinases 2 activities were present in almost all
      samples of aqueous humour (32 of 36) and were 2.6-fold higher in patients who
      suffered from diabetic ocular complications (p < 0.0001). Activities of MMP-2
      correlated well with the duration of the disease (correlation = 0.37, p = 0.03)
      and tended to correlate with total protein levels in aqueous humour (correlation
      = 0.43, p = 0.06). Metalloproteinases 9 activities were observed only in 2 of 7
      patients with proliferative diabetic disease and the enzyme was absent from
      aqueous humour samples of patients without proliferative retinopathy.
      CONCLUSIONS: Increased activities of MMP-2 in aqueous humour of patients with PDR
      may be related to the disease process and support the hypothesis that MMP-2 may
      be of particular importance in diabetic retinal neovascularization. MMP-9 may be
      activated at a certain disease stage only.

PMID- 22371775
TI  - The significance of Y chromosome microdeletion analysis in subfertile men with
      clinical variocele.
AB  - INTRODUCTION: The aim of study is determining the cost-effectiveness of detection
      analysis in the presence of exceptional patients who have mild semen disorders,
      and beware of unnecessary varicocele repairs; and to ascertain whether patients
      with clinical varicocele should undergo Y chromosome (Yq) microdeletion analysis
      as a routine procedure. MATERIAL AND METHODS: Varicocele with reflux was
      diagnosed in 51 male patients with subfertility symptoms upon physical
      examination (PE), confirmed by scrotal colour-Doppler ultrasound (CDU). After
      cytogenetic examination, Yq microdeletion analysis was performed on the
      peripheral blood samples using Promega Y Chromosome Deletion Detection System
      Version 2. Varicocele repair was performed under general anaesthesia with optical
      magnification (3-fold) through a subinguinal approach. RESULTS: The mean age of
      the patients was 27.9. Values of semen concentration ranged from 0 to 72
      million/ml, motility from 0 to 65% (A + B) and Kruger from 0% to 18%. The PE
      revealed normal size and consistency in the bilateral testicles. All patients
      were cytogenetically normal. However, Yq microdeletion was detected in 2
      patients, 1 with mild oligoteratozoospermia and partial AZFb deletion (sY121) and
      the second patient with severe oligozoospermia and partial AZFc deletion (sY254
      and sY255), and they were not subjected to varicocelectomy. CONCLUSIONS: The
      routine performance of pre-operative Yq microdeletion analysis in patients with
      clinical varicocele does not seem to be cost-effective but the omission of
      patients with mild oligozoospermia would have subjected them to an unnecessary
      varicocelectomy and/or further ICSI applications and also would have caused the
      failure of referral for genetic counselling.

PMID- 22371776
TI  - Technique of transurethral needle core biopsy to confirm invasive bladder cancer
      staging.
AB  - INTRODUCTION: Transurethral, cystoscopically-guided needle core biopsy
      (TUcoreBxBT) seems to be a less invasive diagnostic method than transurethral
      resection (TURBT) offering a simple way to confirm cancer infiltration of the
      bladder. The aim of this study was to assess the technique of TUcoreBxBT in the
      diagnosis of bladder cancer infiltrating the detrusor muscle. MATERIAL AND
      METHODS: In every 96 pts the suspicion of invasive bladder cancer (IBC) was
      evaluated on the basis of radiological examinations, cystoscopy and bimanual
      examination. TUcoreBxBT were performed using a rigid cystoscope with a direct
      working channel and tru-cut automatic (COOK Quick-Core((r)) Biopsy-Needle) 18
      G/480 mm needle or self construction tru-cut 16 G/400 mm needle, adapted to work
      with a standard biopsy gun. At least three cores were taken in each patient,
      followed by regular TURBT. RESULTS: There were no complications of the bladder
      biopsy procedure. The average size of cores was 15 mm (8-17 mm). In every case
      TUcoreBxBT revealed muscle infiltration and was in agreement with all microscopic
      examinations of TURBT. CONCLUSIONS: TUcoreBxBT in cases of clear suspicion of
      invasive bladder cancer is a simple, short and safe procedure which makes it
      possible to collect reliable material for microscopic examination. TUcoreBxBT is
      less invasive than standard TURBT only in diagnosis and staging of invasive
      tumours, and seems to be effective in selected cases to confirm malignancy before
      radical cystectomy.

PMID- 22371777
TI  - Functional scoliosis caused by leg length discrepancy.
AB  - INTRODUCTION: Leg length discrepancy (LLD) causes pelvic obliquity in the frontal
      plane and lumbar scoliosis with convexity towards the shorter extremity. Leg
      length discrepancy is observed in 3-15% of the population. Unequalized lower limb
      length discrepancy leads to posture deformation, gait asymmetry, low back pain
      and discopathy. MATERIAL AND METHODS: In the years 1998-2006, 369 children, aged
      5 to 17 years (209 girls, 160 boys) with LLD-related functional scoliosis were
      treated. An external or internal shoe lift was applied. RESULTS: Among 369
      children the discrepancy of 0.5 cm was observed in 27, 1 cm in 329, 1.5 cm in 9
      and 2 cm in 4 children. During the first follow-up examination, within 2 weeks,
      the adjustment of the spine to new static conditions was noted and correction of
      the curve in 316 examined children (83.7%). In 53 children (14.7%) the correction
      was observed later and was accompanied by slight low back pain. The time needed
      for real equalization of limbs was 3 to 24 months. The time needed for real
      equalization of the discrepancy was 11.3 months. CONCLUSIONS: Leg length
      discrepancy equalization results in elimination of scoliosis. Leg length
      discrepancy < 2 cm is a static disorder; that is why measurements should be
      performed in a standing position using blocks of adequate thickness and the
      position of the posterior superior iliac spine should be estimated.

PMID- 22371778
TI  - Is there a gender difference in associates of adolescents' lifetime illicit drug
      use in Tehran, Iran?
AB  - INTRODUCTION: Information regarding gender differences in drug use of adolescents
      is essential for designing gender-specific drug prevention policies. This study
      was conducted in high school students in Tehran, Iran, in 2007. Here, we report
      the gender differences in lifetime prevalence as well as psychosocial associates
      of drug use. MATERIAL AND METHODS: This was a gender analysis of the data
      collected in a drug use survey conducted in a random sample of high school
      adolescents (573 boys and 551 girls) in Tehran, Iran, 2007. Demographic
      characteristics, parental and peers' substance use, school performance, religious
      beliefs, attachment, self-esteem and emotional intelligence (EI) were entered in
      logistic regression analyses to predict the lifetime illicit drug use in boy and
      girls, separately. RESULTS: Boys were more likely to report lifetime illicit drug
      use than girls (10.1% vs. 6.4%, p = 0.023). Differences in the risk profile
      associated with lifetime illicit drug use by gender included history of substance
      use in the family, higher score of attachment, and having an employed mother as
      predictors of substance use in boys, but not girls. CONCLUSIONS: Understanding
      this gender difference in predictors of lifetime use of illicit drugs in high
      school adolescents facilitates the design of gender-sensitive drug use preventive
      programmes. It seems that family variables may have more value in prevention of
      illicit drug use in male adolescents.

PMID- 22371779
TI  - The effects of L-thyroxin replacement therapy on bone minerals and body
      composition in hypothyroid children.
AB  - INTRODUCTION: Prolonged treatment with levothyroxine 4 (L-T4) is a well known
      risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a
      subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones
      directly affect bone cells, stimulating osteoclastic and osteoblastic activity
      with a predominance of bone resorption and decrease of bone mineral density
      (BMD). MATERIAL AND METHODS: The study included 35 hypothyroid patients with mean
      age 11.57 +/-5.06, while 26 age- and sex-matched children served as controls.
      Dual energy X-ray absorptiometry (DXA) was done to detect the bone mineral
      density (BMD), bone mineral content (BMC) and Z score in lumbar and femur neck
      regions. Body composition was also studied by DXA. Calcium, phosphorus,
      osteocalcin as a bone formation marker, osteoprotegerin as an indicator of
      osteoclast activity and urinary deoxypyridinoline as a bone collagen breakdown
      marker were assessed. RESULTS: No significant differences were detected in lumbar
      Z score (-0.12 +/-0.66) and femur Z score (-0.17 +/-0.58) compared to controls (
      0.33 +/-0.74 and -0.21 +/-0.53 respectively). Bone mineral density and BMC were
      not significantly different from controls. No significant difference was detected
      between cases and controls in body composition. A positive correlation was
      detected between BMD and age (r=0.857, p<0.01), and with the period of treatment
      (r=0.766, p<0.01). A positive correlation was found between BMD and total body
      fat (r=0.693, p<0.01), and with abdominal fat (r=0.667, p<0.01). CONCLUSIONS:
      Levothyroxine 4 treatment in hypothyroid children does not alter bone metabolism
      and body composition.

PMID- 22371780
TI  - Successes and pitfalls of chronic peritoneal dialysis in infants - a Polish
      nationwide outcome study.
AB  - INTRODUCTION: Peritoneal dialysis (PD) is a preferred method of renal replacement
      therapy for end-stage renal disease in children. Recent advances have allowed
      chronic PD to be provided to children of all ages and sizes. MATERIAL AND
      METHODS: The study was designed as a national (10 dialysis centres), multicentre
      retrospective analysis of the medical history of 33 children who started chronic
      peritoneal dialysis in their infancy between 1993 and 2005, with a follow-up
      period of at least 24 months. RESULTS: The nutritional status of the infants was
      unsatisfactory. The mean SDS of body weight at the start was -2.0, at 1 year of
      age -1.7. Only 40% of infants were adequately nourished at 1 year of age. Long
      term follow-up analysis showed that 12 children received a kidney transplant, 13
      were still on dialysis (4 changed method) and 6 died (mortality rate in the first
      year of life of 9%). In 2 children we observed an improvement of renal function.
      We observed a relatively high (1/8.8 patient-months) peritonitis rate in the
      analysed children when compared to 1 : 22 patient-months in all children
      undergoing PD in Poland. CONCLUSIONS: The results of our survey have shown that
      the management of dialysed infants is still a challenge for the medical team and
      families, but long-term results of the therapy are encouraging.

PMID- 22371781
TI  - Aluminium and lead abnormalities in children on haemodialysis: relationship with
      some medications.
AB  - INTRODUCTION: The determination of toxic elements in the biological samples of
      human beings is an important clinical procedure. This study was performed to
      investigate the prevalence of abnormal blood contents of 2 trace elements (TEs),
      aluminum (Al),and lead (Pb) in hemodialysis (HD) patients and to analyze their
      relationship with the medications, such as CaCO(3), Ca acetate, 1,25-dihydroxy
      vit. D(3), and erythropoietin (EPO), as well as hematocrit level. MATERIAL AND
      METHODS: We included 43 patients on maintenance HD and they had continued the
      previously mentioned medications for at least 3 months. None of the patients were
      on Al containing phosphate binding agents. RESULTS: Serum aluminum and lead
      levels were significantly increased than in the healthy controls, but levels of
      both of them were far below toxic values. Male patients had higher mean levels of
      lead than did females. A strong positive correlation was found between serum Al
      and serum Pb levels among patients (r = 0.075, p = 0.0001).The serum level of Pb
      was positively correlated with the serum albumin in HD patients (r = 0.45, p =
      0.03). Both serum aluminium and lead levels positively correlated with the EPO
      dose taken by the patients (r = 0.77, p = 0.0001 and r = 0.67, p = 0.0001
      respectively). CONCLUSIONS: The blood level of trace metals of these HD patients
      was not related to their medications except for the EPO dose. However, caution
      must be exercised in interpreting this result as dose and duration of medication
      may play an important role. Al and Pb over load may be considered from the causes
      of inadequate response to epoetin therapy.

PMID- 22371782
TI  - Tumour necrosis factor gene polymorphisms and migraine in Greek children.
AB  - INTRODUCTION: Migraine is considered to be a multifactorial, complex disease.
      Various genetic and environmental factors contribute to the manifestation of this
      disease. The aim of this study was to determine whether polymorphisms in the
      tumour necrosis factor (TNF) region are associated with the risk of migraine. We
      examined the association between 6 single nucleotide polymorphisms in the coding
      regions of TNF-alpha and TNF-beta genes and migraine. MATERIAL AND METHODS: The
      study included two groups of children (group A and group B). Group A consisted of
      103 unrelated children with typical migraine without aura 5-14 years of age.
      Group B (control group) consisted of 178 unrelated healthy children. The
      diagnosis of migraine was, in all patients, made according to the International
      Classification of Headache Disorders (ICHD II). RESULTS: According to our results
      positive family history was present in 62.2% of patients of group A. No
      significant differences were found in the frequencies of genotypes or alleles
      between patients and controls. The non-parametric analyses of variance showed no
      significant differences in the age at onset between genotype groups of the TNF
      alpha and TNF-beta gene polymorphisms. Comparison of genotype frequencies between
      boys and girls in affected patients and control individuals were not
      significantly different (p = 0.089, p =0.073 respectively). The distribution of
      TNF polymorphisms was not associated with the presence of family history of
      migraine in patients. CONCLUSIONS: Our data indicate that TNF-alpha and TNF-beta
      gene polymorphisms are not a significant risk factor for migraine without aura in
      Greek children.

PMID- 22371783
TI  - Normalization of the Verbal Fluency Test on the basis of results for healthy
      subjects, patients with schizophrenia, patients with organic lesions of the
      chronic nervous system and patients with type 1 and 2 diabetes.
AB  - INTRODUCTION: Verbal fluency is the ability to form and express words compatible
      with required criteria. Verbal fluency is necessary for optimal communication and
      for normal social and occupational functioning. The Verbal Fluency Test is a good
      indicator of frontal lobe dysfunction, particularly of the left frontal cortex.
      MATERIAL AND METHODS: The aim of the study was to compare verbal fluency in
      healthy subjects (n = 50), patients with paranoid schizophrenia (n = 36),
      patients with organic lesions of the central nervous system (CNS) (n = 33), and
      patients with diabetes (n = 62) - type 1 diabetes (n = 31) and type 2 diabetes (n
      = 31). RESULTS: Healthy subjects and patients with diabetes achieved the highest
      results in all categories of the Verbal Fluency Test. Patients with paranoid
      schizophrenia achieved significantly lower results. Sten norms of the Verbal
      Fluency Test were developed for the general population. Using these norms it was
      found that subjects with schizophrenia or with organic lesions of the CNS had
      very poor results more often and very high results less frequently compared to
      healthy subjects and also to patients with diabetes. CONCLUSIONS: This
      observation is consistent with the neurodevelopmental hypothesis of
      schizophrenia, in which cognitive functions of the frontal lobe (e.g. verbal
      fluency) play a major role in the psychopathological picture. We have also
      demonstrated that in patients with type 1 and 2 diabetes verbal fluency is
      comparable with healthy subjects.

PMID- 22371784
TI  - Endogenous reward mechanisms and their importance in stress reduction, exercise
      and the brain.
AB  - Stress can facilitate disease processes and causes strain on the health care
      budgets. It is responsible or involved in many human ailments of our time, such
      as cardiovascular illnesses, particularly related to the psychosocial stressors
      of daily life, including work. Besides pharmacological or clinical medical
      treatment options, behavioral stress reduction is much-needed. These latter
      approaches rely on an endogenous healing potential via life-style modification.
      Hence, research has suggested different ways and approaches to self-treat stress
      or buffer against stressors and their impacts. These self-care-centred approaches
      are sometimes referred to as mind-body medicine or multi-factorial stress
      management strategies. They consist of various cognitive behavioral techniques,
      as well as relaxation exercises and nutritional counselling. However, a critical
      and consistent element of modern effective stress reduction strategies are
      exercise practices. With regard to underlying neurobiological mechanisms of
      stress relief, reward and motivation circuitries that are imbedded in the limbic
      regions of the brain are responsible for the autoregulatory and endogenous
      processing of stress. Exercise techniques clearly have an impact upon these
      systems. Thereby, physical activities have a potential to increase mood, i.e.,
      decrease psychological distress by pleasure induction. For doing so,
      neurobiological signalling molecules such as endogenous morphine and coupled
      nitric oxide pathways get activated and finely tuned. Evolutionarily, the various
      activities and autoregulatory pathways are linked together, which can also be
      demonstrated by the fact that dopamine is endogenously converted into morphine
      which itself leads to enhanced nitric oxide release by activation of constitutive
      nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress
      reducing.

PMID- 22371786
TI  - Thoraco-omphalopagus twins: different perinatal circumstances, different outcome.
AB  - Two pairs of omphalopagus twins were encountered at the Polish Mother's Health
      Institution in Lodz, Poland during the past 15 years. In the first set the
      prenatal diagnosis was not established and the delivery of the twins in a
      regional hospital was a complete surprise. Both babies died. In the second case
      the conjoined twins were diagnosed prenatally, surgical separation was
      successful, and both twins survived. The prenatal identification of conjoined
      twins is of cardinal importance for the planning of delivery and possible
      separation.

PMID- 22371785
TI  - Opioid peptides and opiate alkaloids in immunoregulatory processes.
AB  - Among the various non-neuronal cell types known to express and utilize
      neuropeptides, those of the immune system have received much attention in recent
      years. In particular, comparative studies in vertebrates and invertebrates have
      shown that endogenous opioid peptides are engaged in receptor mediated
      autoregulatory immune and neuroendocrine processes. The majority of these immune
      processes are stimulatory, as determined by their effects on conformational
      changes indicative of immunocyte activation, cellular motility, and phagocytosis.
      Endogenous opioid peptides form an effective network of messenger molecules in
      cooperation with cytokines, opiate alkaloids, and certain regulatory enzymes
      (neutral endopeptidase 24.11). Peptide-mediated immunostimulatory effects
      observed in this system are operationally counteracted by the inhibitory effects
      of morphine and related opiates. Opioid/opiate signaling processes are mediated
      by several types of receptors with different degrees of selectivity. Among them
      the recently identified, opioid insensitive u(3) receptor deserves attention on
      account of its specificity for opiate alkaloids.

PMID- 22371787
TI  - Chronic mucocutaneous candidiasis with endocrinopathy - case report.
AB  - Chronic mucocutaneous candidiasis (CMC) is characterized by Candida infection of
      the mucous membrane, scalp, skin and nails. We present a case of a 42-year-old
      man who was treated twice in the Dermatological Department. He was admitted the
      first time as a 7-year-old boy because of skin and mucosal lesions and then the
      diagnosis of granuloma candidamyceticum was established. Thirty-one years later
      he was admitted again with a history of facial skin lesions and blepharitis. For
      a couple of years he had suffered from diabetes and hypothyroidism. The diagnosis
      of CMC with endocrinopathy was established in our patient.

PMID- 22371788
TI  - Preclinical and clinical evidence of nephro- and cardiovascular protective
      effects of glycosaminoglycans.
AB  - Despite advances in pharmacological treatment, diabetic nephropathy is still the
      leading cause of end-stage renal disease and an important cause of morbidity and
      mortality in diabetics. Glycosaminoglycans are long, unbranched
      mucopolysaccharides that play an important role in establishing a charge
      selective barrier that restricts the passage of negatively charged molecules,
      such as albumin and other proteins, at the level of the glomerular basal
      membrane. Their loss is associated with loss of selectivity and proteinuria.
      Extensive preclinical evidence and some clinical trials suggest that
      glycosaminoglycans replacement is associated with improvement of glomerular
      selectivity and of proteinuria. Sulodexide could also have some other effects,
      potentially useful to reduce the renal damage and the cardiovascular disease
      associated with proteinuria, such as improvement of haemorheological and blood
      lipid parameters, an endothelium protective effect and anti-inflammatory action.
      This review will discuss the evidence supporting the potential nephroprotective
      effects of sulodexide and other glycosaminoglycans.

PMID- 22371789
TI  - Biological indications of a novel "short" u opiate receptor in domestic chicken.
AB  - Previous work from our laboratory has established that cellular signaling
      processes of endogenous morphine are mediated by cognate G protein coupled
      receptor (GPCR) proteins, designated u(3) and u(4) opiate receptors. u(3) and
      u(4) opiate receptors are structurally unique "short" 6 transmembrane helical
      (TMH) domain GPCRs that are selectively responsive to endogenous morphine, not to
      families of endogenous opioid peptides, and are uniquely coupled to activation of
      constitutive nitric oxide synthase (cNOS). Based on high resolution predictive
      measures, it appears likely that domestic poultry express a u opiate receptor
      mRNA encoding potentially two novel GPCRs with similar biochemical
      characteristics as described for u(3) and u(4) opiate receptors as well as
      traditional u(1) opioid receptors. The biological indications of these novel u
      opiate receptors are discussed within the context of this short review.

PMID- 22371790
TI  - Air pollution and non-respiratory health hazards for children.
AB  - Air pollution is a global health issue with serious public health implications,
      particularly for children. Usually respiratory effects of air pollutants are
      considered, but this review highlights the importance of non-respiratory health
      hazards. In addition to short-term effects, exposure to criteria air pollutants
      from early life might be associated with low birth weight, increase in oxidative
      stress and endothelial dysfunction, which in turn might have long-term effects on
      chronic non-communicable diseases. In view of the emerging epidemic of chronic
      disease in low- and middle- income countries, the vicious cycle of rapid
      urbanization and increasing levels of air pollution, public health and regulatory
      policies for air quality protection should be integrated into the main priorities
      of the primary health care system and into the educational curriculum of health
      professionals.

PMID- 22371791
TI  - Myeloma cells inhibit osteogenic differentiation of mesenchymal stem cells and
      kill osteoblasts via TRAIL-induced apoptosis.
AB  - INTRODUCTION: Myeloma bone disease (MBD) is the result of the increased activity
      of osteoclasts (OCs), which is not accompanied by a comparable increase of
      osteoblast (OB) function, thus leading to enhanced bone resorption. Osteoblasts
      can also regulate osteoclast activity through expression of cytokines, such as
      receptor activator of nuclear factor-kappaB ligand (RANKL), which activates
      osteoclast differentiation, and osteoprotegerin (OPG), which inhibits RANKL by
      acting as a decoy receptor. MATERIAL AND METHODS: Based on a series of 21
      patients with multiple myeloma (MM) and human osteoblast cell line HFOB1.19, we
      provide evidence that the bone marrow-derived mesenchymal stem cells (BMMSCs) of
      patients with MM exhibit normal phenotype, but showed reduced efficiency to
      differentiate into OBs as compared with normal controls. RESULTS: In vitro assays
      showed that MM cells inhibited the potential of osteogenic differentiation of
      BMMSCs from healthy controls and rendered the OBs sensitive to TRAIL-induced
      apoptosis. There was no evidence of the formation of tartrate-resistant acid
      phosphatase positive OCs. The osteogenic differentiation of HFOB1.19 was also
      inhibited in the presence of RPMI 8266 or XG7 MM cells, as confirmed by von Kossa
      and ALP staining. Osteoblast s induced from BMMSCs supported survival and
      proliferation of MM cells, especially when the MM cells were cultured in medium
      containing rhTRAIL and dexamethasone. Multiple myeloma cells proliferated and
      grew well in the presence of residual OBs. CONCLUSIONS: Besides OCs, our results
      demonstrated that OBs and MM cells were dependent upon each other and made a
      microenvironment suitable for MM cells.

PMID- 22371792
TI  - Vitamin E reversed nicotine-induced toxic effects on bone biochemical markers in
      male rats.
AB  - INTRODUCTION: Vitamin E is beneficial in restoring bone histomorphometric
      parameters in nicotine-treated rats. This study determined the effectiveness of 3
      forms of vitamin E in restoring bone metabolism in nicotine-treated rats.
      MATERIAL AND METHODS: Thirty-five male Sprague-Dawley rats were divided into 5
      groups: (1) control (C), (2) nicotine cessation (NC), (3) alpha-tocopherol (ATF),
      (4) tocotrienol-enhanced fraction (TEF) and (5) gamma-tocotrienol (GTT).
      Treatment was carried out for 4 months. The control group was administered normal
      saline and olive oil throughout the treatment period while treatment for groups 2
      5 was performed in 2 phases. In the first phase, the groups received nicotine 7
      mg/kg intraperitoneally for 2 months. The following 2 months, group 2 received
      normal saline and olive oil while groups 3-5 received ATF, TEF or GTT, 60 mg/kg
      orally. Pre-treatment and post-treatment serum was collected for bone biochemical
      marker measurement using the ELISA method. RESULTS: Nicotine increased serum bone
      resorbing cytokines (interleukin-1 and interleukin-6) and the bone resorption
      marker pyridinoline (PYD) while reducing the bone formation marker osteocalcin
      after 2 months of nicotine treatment. The parameters failed to improve after
      nicotine was stopped for 2 months. Supplementation with the 3 forms of vitamin E
      improved the parameters, i.e. reduced the cytokines and pyridinoline as well as
      increased the osteocalcin. In addition, the TEF and GTT groups had a higher level
      of osteocalcin than the control group. CONCLUSIONS: Nicotine impaired bone
      metabolism and cessation of nicotine treatment did not reverse the effects.
      Vitamin E, especially the tocotrienols, restored bone metabolism that was
      impaired due to nicotine.

PMID- 22371793
TI  - Effects of coenzyme Q10 supplementation on activities of selected antioxidative
      enzymes and lipid peroxidation in hypertensive patients treated with indapamide.
      A pilot study.
AB  - INTRODUCTION: An increase in oxidative stress is strongly documented in
      hypertensive patients. In blood vessels, oxidative stress increases the
      production of superoxide anion (O(2) (*-)) that reacts with nitric oxide (NO) and
      impairs the ability of endothelium to relax. Many reports indicate a beneficial
      effect of coenzyme Q10 (CoQ) in hypertension. Coenzyme Q10 therapy may lower O(2)
      (*-) and thus decrease the complications associated with hypertension. The aim of
      our study was to evaluate the effects of CoQ supplementation on antioxidative
      enzyme activities and lipid peroxidation in elderly hypertensive patients.
      MATERIAL AND METHODS: We determined the activities of superoxide dismutase (SOD
      1) and glutathione peroxidase (GSH-Px) and the concentration of malondialdehyde
      (MDA) in erythrocytes of 27 elderly (mean age 72.5 +/-6.1 year) hypertensive
      patients treated with indapamide at baseline and after 12 weeks of CoQ
      supplementation (60 mg twice a day) in comparison with 30 healthy elderly
      volunteers (mean age 76.8 +/-8.5 year). RESULTS: Decrease of SOD-1 (p < 0.001)
      and insignificant reduction of GSH-Px activities and increase of MDA (p < 0.001)
      level were observed in hypertensive patients in comparison to healthy volunteers
      before supplementation. Coenzyme Q10 administration resulted in a significant
      increase only in SOD-1 activity (p < 0.001). CONCLUSIONS: The present study
      indicates that CoQ improves the most important component of the antioxidant
      defence system - SOD-1, which is responsible for O(2) (*-) scavenging. Coenzyme
      Q10 may be used as an additional therapeutic agent for prophylaxis and treatment
      of hypertension in elderly patients.

PMID- 22371794
TI  - Evaluation of left ventricular dyssynchrony using combined pulsed wave and tissue
      Doppler imaging.
AB  - INTRODUCTION: The combination of pulsed wave (PW) and tissue Doppler imaging
      (TDI) has been proposed as a new method to assess left ventricular (LV)
      mechanical dyssynchrony (LVMD), but results have not been validated. We
      investigated the correlation of a combination of PW and TDI with a positive
      response to cardiac resynchronization therapy (CRT). MATERIAL AND METHODS: We
      studied 108 consecutive patients who received CRT. Patients with atrial
      fibrillation were excluded. The time difference (T(PW-TDI)) between onset of QRS
      to the end of LV ejection by PW (T(PW)) and onset of QRS to the end of the
      systolic wave in LV basal segments with greatest delay by TDI (T(TDI)) was
      measured before CRT and during short-term and long-term follow-up. RESULTS: The
      T(PW-TDI) interval before CRT was 74 +/-48 ms. Intra-observer variabilities for
      T(PW) and T(TDI) were 1.5 +/-0.24% and 1 +/-0.17%. Inter-observer variabilities
      for T(PW) and T(TDI) were 1 +/-0.36% and 1 +/-0.64%, respectively. T(PW-TDI) > 50
      ms was defined as the cutoff value for diagnosis of LVMD by receiver operating
      curve (ROC) analysis. During follow-up of 15 +/-11 months, the sensitivity and
      specificity of TP(PW-TDI) to predict a positive response to CRT were 98% and 82%,
      respectively. The area under the ROC curve was 0.92. There was a significant
      agreement between LVMD determined by T(PW-TDI) and the positive response to CRT
      (kappa=0.80). CONCLUSIONS: Left vertricular dyssynchrony detected by the method
      combining PW and TDI demonstrated a high reproducibility, sensitivity,
      specificity and agreement with a positive response to CRT.

PMID- 22371795
TI  - Changes in transforming growth factor beta and its receptors' mRNA expression in
      monocytes from patients with acute coronary syndromes.
AB  - INTRODUCTION: Transforming growth factor beta (TGF-beta) is thought to be a
      vasoprotective cytokine. Numerous reports confirm its significance in blood and
      plaques. There is, however, a lack of information on the molecular mechanisms
      involving TGF-beta in circulating inflammatory cells in atherogenesis. sThe aim
      of the study was to assess gene expression of TGF-beta and its receptors in
      monocytes from patients with acute coronary syndromes (ACS) and the effect of
      standard treatment on the studied genes. MATERIAL AND METHODS: The study was
      carried out in 32 patients with ACS and 15 healthy subjects. Gene expression of
      TGF-beta and receptors TGF-betaRI and TGF-betaRII was evaluated on day 1 and 5 in
      the study group and once in controls. The number of mRNA copies isolated from
      monocytes was assessed by QRT-PCR. RESULTS: Monocytes of ACS patients showed
      slightly elevated transcriptional activity of TGF-beta1 and its receptors RI and
      RII genes (0.29 +/-0.043 vs. 0.08 +/-0.020, p = 0.05; 0.071 +/-0.022 vs. 0.036 +/
      0.023, p < 0.05; 0.134 +/-0.020 vs. 0.048 +/-0.016, p < 0.05, respectively).
      After 5-day standard treatment modest reduction of TGF-betaRI expression was
      observed. The studied genes' expression was unrelated to ejection fraction,
      myocardial necrosis markers, GRACE score, time from the onset of pain to
      percutaneous coronary intervention and angiographic findings. Among risk factors
      family history of CAD was associated with increased TGF-betaRI expression.
      Moreover, the presence of 4 or more classic risk factors correlated with higher
      TGF-betaRI expression. CONCLUSIONS: Monocytes of ACS patients demonstrate
      overexpression of TGF-beta1 and its receptors' genes. Five-day standard treatment
      downregulated the TGF-betaRI gene but did not affect TGF-beta1 and TGF-betaRII.

PMID- 22371796
TI  - Renal vascular response to angiotensin II inhibition in intensive
      antihypertensive treatment of essential hypertension.
AB  - INTRODUCTION: High blood pressure (BP) leads to target organ damage. It is
      suggested that regression of early organ lesions is possible on condition of BP
      normalization. The study objective was to assess whether permanent reduction of
      BP to the recommended values modifies renal vascular response to acute
      angiotensin II inhibition in the Doppler captopril test (DCT) in patients with
      essential hypertension (EH). MATERIAL AND METHODS: Twenty-nine persons (58
      kidneys) were found eligible for the study: 18 patients with EH and 11 healthy
      volunteers constituting the control group. Glomerular filtration rate estimation
      (eGFR), 24-h ambulatory BP monitoring (ABPM) and DCT with evaluation of renal
      resistive index change (DeltaRI) were performed before and after a 6-month period
      of intensive antihypertensive therapy (IAT). Additional ABPM was performed at the
      end of IAT. RESULTS: The mean IAT period was 8.5 +/-2.4 months. The mean 24-h
      values of systolic and diastolic BP in the EH group were significantly lower in
      the IAT period than at the beginning and at the end of the study. Significantly
      lower systolic and diastolic BP (p < 0.05) and improvement of renal function
      (eGFR 121 +/-38 vs. 139 +/-40 ml/min, p < 0.001) were found after IAT as compared
      to initial values. Before IAT, DeltaRI was significantly lower in the EH group as
      compared to the controls, but no such differences were found after IAT.
      CONCLUSIONS: In EH patients, intensive BP lowering to the recommended values was
      associated with improvement of renal function and normalisation of renal vascular
      response to acute angiotensin II inhibition.

PMID- 22371797
TI  - The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed
      patients.
AB  - INTRODUCTION: Anaemia is one of the arms of the cardio-renal-anaemia syndrome
      (CRA) in chronic kidney disease (CKD) patients. The correction of anaemia was
      effective in the amelioration of both cardiac and renal failure. We studied the
      relationship between the severity of CRA syndrome in peritoneally dialyzed
      patients and their survival probability. MATERIAL AND METHODS: Fifty-six patients
      on peritoneal dialysis were followed for 1 year. Definition of the severity of
      the CRA in dialysis patients: cardiac arm - NYHA class I-IV = 1-4 points, renal
      arm - non-diabetic patients age < 65 =1 point, non-diabetic patients age>65 = 2
      points, diabetic patients age < 65 = 3 points, diabetic patients age>65 = 4
      points, anaemia arm - Hb 11-13 g/dl (male), 11-12 g/dl (female) = 1 point, Hb 10
      11 g/dl = 2 points, Hb 9-10 g/dl = 3 points, Hb < 9 g/dl = 4 points. The severity
      score = cardiac + renal + anaemia arms score divided by 3 (maximum 4 points).
      RESULTS: A total of 10/56 patients (18%) died during the study. The median value
      for the severity score of the whole group was 1.69. In Kaplan-Meier analysis CRA
      severity score was strongly associated with mortality (p < 0.001). It also
      correlated with albumin, CRP, erythropoietin treatment, Hb and fasting glucose.
      In the multivariate regression analysis age, Hb, albumin, and presence of
      diabetes remained significant predictors of death. CONCLUSIONS: The severity
      score of CRA syndrome in peritoneally dialyzed patients is an independent and
      very significant predictor of death. The patients with a high severity score had
      more hypoalbuminaemia, higher inflammation markers and higher prevalence of
      diabetes and chronic heart failure. Cardio-renal-anaemia syndrome severity
      scoring as defined by us could be an easy tool to predict outcome of dialysis
      patients.

PMID- 22371798
TI  - TRAIL protein expression in breast cancer cells correlates with nuclear grade.
AB  - INTRODUCTION: TRAIL protein may serve as an escape mechanism for cancer cells
      from the immune response. The aim of the study was to assess whether the presence
      of TRAIL protein correlates with unfavourable prognostic factors in breast
      carcinoma. MATERIAL AND METHODS: The study group was composed of breast cancer
      patients treated surgically in the Department of Surgical Oncology, Medical
      University of Lodz, Poland, from January to December 2003. Inclusion criteria for
      the study were fulfilled by 117 women. The immunohistochemical study of TRAIL
      protein expression was performed in 118 breast carcinomas diagnosed in the study
      group. TRAIL protein expression was correlated with other variables: tumour size,
      lymph node status, grade, histological type of carcinoma, oestrogen and
      progesterone receptor status, HER2 expression, presence of lymphovascular
      invasion and age of the patient. RESULTS: Expression of TRAIL protein was present
      in 73% of breast carcinomas. The percentage of TRAIL-expressing breast carcinoma
      cells correlated with the nuclear grade (tau = 0.26, p < 0.05; Tau Kendall test).
      The intensity of TRAIL expression (intensity of staining) in breast carcinoma
      cells correlated with the nuclear grade (tau = 0.15, p < 0.05; Tau Kendall test).
      TRAIL expression in breast carcinoma did not correlate with other studied
      variables. CONCLUSIONS: Our analysis revealed that expression of TRAIL protein in
      breast carcinoma cells correlates with nuclear grade of carcinoma.

PMID- 22371799
TI  - IL-1beta, IL-6 promoter, TNF-alpha promoter and IL-1RA gene polymorphisms and the
      risk of preterm delivery due to preterm premature rupture of membranes in a
      population of Polish women.
AB  - INTRODUCTION: Our previous study revealed that anti-inflammatory cytokine gene
      polymorphisms increase the risk of spontaneous preterm delivery (PD) in a
      population of Polish women. Different genetic background of PD due to preterm
      premature rupture of membranes (pPROM) than PD without pPROM has been suggested.
      The aim of this study was to examine the relationship between the maternal
      carriage of polymorphic alleles of the following genes: interleukin 1beta(IL
      1beta [+3953C>T]), interleukin 6 promoter (IL-6 [-174G>C]), tumour necrosis
      factor promoter (TNF-alpha [-308G>A]) and interleukin 1 receptor antagonist (IL
      1RN) and the risk of PD caused exclusively by pPROM in a population of Polish
      women. MATERIAL AND METHODS: A case-control study. 95 Caucasian women were
      examined including 32 cases and 63 controls. Case subjects experienced a delivery
      at less than 36 weeks and 6 days of gestation due exclusively to pPROM while
      control subjects gave birth at term. Polymorphisms were determined by polymerase
      chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP).
      RESULTS: NO STATISTICALLY SIGNIFICANT RELATIONSHIP BETWEEN POLYMORPHISMS OF
      EXAMINED GENES AND RISK OF PD DUE TO PPROM IN A POPULATION OF POLISH WOMEN WAS
      FOUND: OR = 0.84 (95% CI: 0.34-2.01) for IL-1beta, OR = 0.77 (95% CI: 0.27-2.13)
      for IL-6, OR = 0.72 (95% CI: 0.26-1.90) for TNF-alpha and OR = 1.74 (95% CI: 0.66
      4.64) for IL-1RN. CONCLUSIONS: Maternal carriage of polymorphic alleles of IL
      1beta, IL-6 promoter, TNF-alpha promoter and IL-1RA seems to have no impact on
      the risk of PD due to pPROM in the population of Polish women.The genetic
      contribution and pathomechanism of PD related to pPROM seems to differ from those
      of spontaneous PD without pPROM.

PMID- 22371800
TI  - Cord blood resistin and adiponectin in term newborns of diabetic mothers.
AB  - INTRODUCTION: Adipose tissue can release hormones into the blood stream in
      response to specific extracellular stimuli or changes in metabolic status.
      Resistin, an adipose-secreted factor, is primarily involved in the modulation of
      insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte
      specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic
      effects, is reduced in obesity and type II diabetes. The aim of the study was to
      assess the influence of maternal pre-existing diabetes on cord blood resistin and
      adiponectin at birth in relation to neonatal anthropometric parameters and cord
      blood insulin levels. MATERIAL AND METHODS: A total of 60 term newborns were
      prospectively enrolled and categorized into three groups: 20 were macrosomic
      infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic
      infants of pre-gestational diabetic mothers (group II) and 20 were healthy non
      macrosomic infants born to non-diabetic mothers serving as controls (group III).
      Infants' anthropometric indices were recorded. Cord blood samples for glucose,
      insulin, resistin and adiponectin assay, together with maternal glycosylated
      haemoglobin were obtained. RESULTS: Serum insulin was increased while resistin
      and adiponectin were significantly decreased in infants of diabetic mothers
      (IDMs) compared to the control group. Serum glucose, insulin, resistin and
      adiponectin were comparable in group I and II. Cord serum resistin correlated
      positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic
      groups. Cord serum insulin correlated positively with triceps skinfold thickness
      in all studied neonates. Cord serum resistin and adiponectin showed no
      correlation with neonatal anthropometric indices. Multiple regression analysis
      demonstrated that insulin, resistin and adiponectin together were highly
      correlated with birth weight, with adiponectin as the one responsible for this
      positive correlation. CONCLUSIONS: Infants of diabetic mothers had elevated
      levels of cord serum insulin and suppressed levels of cord serum resistin and
      adiponectin, suggesting that the regulation of these metabolic pathways is
      probably operational before birth. Levels were comparable in both macrosomic and
      non-macrosomic neonates.

PMID- 22371801
TI  - Assessment of right atrial and right ventricular size in children after
      percutaneous closure of secundum atrial septal defect with Amplatzer septal
      occluder.
AB  - INTRODUCTION: The aim of this study was to evaluate the right atrial (RA) and
      right ventricular (RV) size, and the speed of their normalization, in children
      after percutaneous closure of secundum atrial septal defect with the Amplatzer
      septal occluder. MATERIAL AND METHODS: The study group consisted of 42 children,
      aged 4.5 to 18.5 years. The following measurements (indexed to body surface area)
      were performed using 2D echocardiography: longitudinal, transverse axis and area
      of RA, RV inflow dimensions at one-third, and halfway between the tricuspid
      annulus and the apex (in the apical 4-chamber view), short axis and M-mode RV
      diastolic dimensions. All measurements were obtained 24 h and 1, 3 and 12 months
      after the procedure, then annually over 4 years of follow-up, and compared with
      the values obtained from the control groups. RESULTS: A significant decrease in
      all RA and RV values was observed after 24 h. Right ventricular transverse
      dimension normalized after 1 month, the RA longitudinal axis and area and the RV
      inflow dimensions after 3 months, and the RA transverse axis and M-mode RV
      diastolic dimension after 2 years, but the ratio of transverse to longitudinal RA
      axis remained significantly higher. CONCLUSIONS: Right atrial and right
      ventricular measurements decrease rapidly during the first 24 h, and most of them
      normalize within a 3-month period. M-mode RV diastolic dimension does not capture
      the real RV changes. Amplatzer septal occluder closure of ASD influences the RA
      geometry, which is reflected by the higher transverse to longitudinal RA axis
      ratio.

PMID- 22371802
TI  - Cyclosporine A - treated nephrotic children show impaired vasodilatation but no
      autonomic neuropathy.
AB  - INTRODUCTION: The aim of the study was to determine the effect of long-term
      cyclosporine A (CsA) treatment in children with idiopathic nephrotic syndrome on
      autonomic nerve function and peripheral blood flow assessed with thermography.
      MATERIAL AND METHODS: The study group consisted of 19 nephrotic children treated
      with cyclosporine A compared to 16 healthy children. The assessment of blood flow
      was made based on the results of thermographic measurements during the cold
      stress test by an infrared radiation registering camera. Ewing's battery of non
      invasive tests was used to assess autonomic function. RESULTS: The study showed
      diminished temperature increase after the cooling test in children with nephrotic
      syndrome treated with CsA. Sympathetic activity test results were comparable to
      healthy children. CONCLUSIONS: It may be hypothesized that cyclosporine A
      administered even in low doses induces small vessel dysfunction measured by the
      thermographic method. This effect seems to be independent of sympathetic nervous
      system involvement, which was absent in cyclosporine A treated nephrotic
      children.

PMID- 22371803
TI  - Hyponatraemia in cases of children with pneumonia.
AB  - INTRODUCTION: Hyponatraemia is the most common electrolyte imbalance seen in
      clinical practice, and a common laboratory finding in children with community
      acquired pneumonia (CAP). This study aimed to identify the incidence of
      hyponatraemia in cases of CAP, to find predictive tools in order to classify the
      severity and outcome of CAP and to explore possible differences of clinical
      importance between the two sexes. MATERIAL AND METHODS: The medical files of 54
      children (66.4% males), 4.67 +/-2.88 years old, were retro-prospectively
      reviewed. RESULTS: 35/54 (64.8%) children with pneumonia had normal values of
      sodium at admission, 18/54 (33.3%) had mild hyponatraemia and 1 child (1.9%)
      moderate hyponatraemia. Increased heart rhythm and tachypnoea at admission were
      correlated with lower values of sodium (z= -2.664, p = 0.007 and z = -1.705, p =
      0.089 respectively). No differences were found between the two sexes concerning
      the characteristics of pneumonia or the range of sodium in serum at admission. A
      correlation was found between sodium admission values and: a) C-reactive protein
      (p = 0.000), and b) leukocyte count (p = 0.006). Sedimentation rate (p = 0.021)
      was also considered as a possible risk factor affecting the value of sodium at
      admission to hospital. Finally, a negative association was also observed between
      the degree of hyponatraemia and the duration of hospitalization (z = -3.398, p =
      0.001). CONCLUSIONS: Although studies in larger population groups are needed, in
      our study increased heart rhythm, tachypnoea, leucocyte count, C-reactive
      protein, and also erythrocyte sedimentation rate could be considered as possible
      risk factors influencing the degree of hyponatraemia, and thus the outcome of
      hospitalized children with CAP.

PMID- 22371804
TI  - Predictors of bone disease in Egyptian prepubertal children with beta
      thalassaemia major.
AB  - INTRODUCTION: Thalassaemic osteopathy is a multifactorial disorder and limited
      information exists about bone accrual and bone mineral density (BMD) in
      prepubertal thalassaemic children. The study aimed to investigate some potential
      genetic and biochemical bone markers as possible early predictors of BMD
      variations in children with beta-thalassaemia major (TM) before puberty. MATERIAL
      AND METHODS: Thirt-one prepubertal children with beta-TM, and 43 matched controls
      were subjected to BMD assessment by dual energy X-ray absorptiometry (DEXA).
      Vitamin D receptor (VDR) gene polymorphisms (Bsm1, Fok1) and the biochemical bone
      markers serum osteocalcin and propeptide I procollagen (CPIP) and urinary
      deoxypyridinoline (DPD) excretion were assessed. RESULTS: Bone mineral density
      was reduced in 25% of thalassaemics at the spine and 15.4% at the hip region.
      Significantly higher levels of urinary DPD and lower serum osteocalcin and CPIP
      levels were found in the studied thalassaemic children compared to controls (p <
      0.001). A significant negative correlation was present between BMD in spine and
      hip and the patients' age (r = -0.6367, p = 0.0002 and r = -0.616, p = 0.00079,
      respectively). There was a significant reduction in BMD in males compared to
      females. Reduced BMD was more frequent in male patients with genotypes bb and Ff
      but not in females. Bone mineral density was not related to the studied
      biochemical bone markers, mean pre-transfusion haemoglobin or serum ferritin.
      CONCLUSIONS: Routine BMD screening with DEXA is proposed to be a sensitive
      predictor for early bone changes, particularly at the lumbar spine. DR gene
      polymorphisms of Bsm1 and Fok1 polymorphisms may be determinants of BMD in
      Egyptian prepubertal male thalassemics.

PMID- 22371805
TI  - Red cell alloimmunization and autoantibodies in Egyptian transfusion-dependent
      thalassaemia patients.
AB  - INTRODUCTION: The objective of this study was to explore the frequency of red
      cell alloantibodies and autoantibodies among beta-thalassaemia patients who
      received regular transfusions. MATERIAL AND METHODS: This study included 501
      patients with beta-thalassaemia. This work planned to study the presence of
      alloantibodies and autoantibodies to different red cell antigens in
      multitransfused thalassaemia patients using the ID. Card micro typing system.
      RESULTS: Of a total of 501 beta-thalassaemia patients included in the study,
      11.3% of patients developed alloantibodies; 9.7% of these alloantibodies were
      clinically significant. The most common alloantibodies were anti-K, anti-E and
      anti-C. The rate of incidence of these alloantibodies was 3.9%, 3.3% and 1.7%
      respectively. Autoantibodies occurred in 28.8% of the patients and 22.1% of these
      antibodies were typed IgG. There was a significant association between
      splenectomy with alloimmunization and autoantibody formation (p = 0.03, p = 0.001
      respectively). There was no significant association between alloantibody,
      autoantibody formation and number of transfused packed red cells. CONCLUSIONS:
      Alloimmunization to minor erythrocyte antigens and erythrocyte autoantibodies of
      variable clinical significance are frequent findings in transfused beta
      thalassaemia patients. There is an association between absence of the spleen and
      the presence of alloimmunization and autoantibody formation.

PMID- 22371806
TI  - Effectiveness comparison of endoscopic methods of non-varicose upper
      gastrointestinal bleeding treatment.
AB  - INTRODUCTION: In every case of upper gastrointestinal bleeding suspicion, an
      endoscopic examination ought to be performed as a matter of urgency. Finding
      active bleeding, a visible non-bleeding vessel or a lesion with an adherent clot
      should be followed by application of an available method of endoscopic therapy.
      The aim of the study was to compare the effectiveness of various endoscopic
      treatment techniques such as epinephrine injections, coagulation methods and
      mechanical methods in the treatment of non-varicose upper gastrointestinal
      bleeding. MATERIAL AND METHODS: Sixty cases of non-varicose upper
      gastrointestinal bleeding were analysed in terms of the effectiveness of the
      above-mentioned procedures used in monotherapy or in combination therapy
      comprising epinephrine injections and clips application. The choice of the
      applied procedure depended on morphological features and location of the bleeding
      source, the patient's general condition, as well as technical equipment and
      manual skills of the endoscopy staff. RESULTS: The study confirmed the
      effectiveness of endoscopic treatment of non-varicose upper gastrointestinal
      bleeding applying the above-mentioned methods. In most patients, this treatment
      enabled traumatic surgical intervention to be avoided; it was required in only 3
      (5%) out of 60 patients with confirmed upper gastrointestinal bleeding. With the
      first endoscopy, haemostasis was achieved in 47 cases (78.3%) and the second
      endoscopy, performed due to bleeding recurrence, was successful in the remaining
      10 cases (16.7%). CONCLUSIONS: In non-varicose upper gastrointestinal bleeding,
      urgent diagnostic and therapeutic endoscopy should be the first-line management.
      If the lesion that is the source of bleeding is possible to localize, the
      endoscopic techniques should be applied. Among the endoscopic procedures used in
      monotherapy, clips appeared to be the most effective, their effectiveness being
      comparable to combination therapy. In bleeding from extensive lesions,
      coagulation methods are considered to be the most efficacious.

PMID- 22371807
TI  - Risk of colorectal cancer in relation to frequency and total amount of red meat
      consumption. Systematic review and meta-analysis.
AB  - INTRODUCTION: The colon and rectum are common sites of food-related cancer in
      developed countries. Recent studies strongly suggest that red meat intake is
      associated with colon cancer, whereas for rectal cancer such an association still
      needs to be proved. The aim of the study was to assess the role of total amount
      and frequency of red meat intake in colorectal carcinogenesis based on published
      data using meta-analysis methods. MATERIAL AND METHODS: The literature published
      until 2009 was selected from: MEDLINE, PubMed, Scopus, Embase, CancerLit, Google
      Scholar and Cochrane Library databases. The used search terms were: colorectal
      cancer, colon cancer, rectal cancer, meat intake, red meat intake, red meat
      consumption, meat consumption, colorectal cancer risk, colon cancer risk, rectal
      cancer risk and lifestyle. Articles investigating red meat intake of more often
      than once a day or 50 g per day were reviewed and selected for further analysis.
      RESULTS: Twenty-two studies fulfilled the established criteria. A meta-analysis
      confirmed the carcinogenic effect of the consumption of over 50 g of red meat per
      day for the colon (relative risk 1.21, 1.07-1.37) but not for the rectum
      (relative risk 1.30, 0.90-1.89). Red meat intake more frequently than once a day
      can induce both colonic (relative risk 1.37, 1.09-1.71) and rectal cancer
      (relative risk 1.43, 1.24-1.64). CONCLUSIONS: Red meat intake is associated with
      elevated risk of developing colorectal cancer. The frequency of red meat
      consumption rather than total amount of consumed meat is associated with a higher
      risk of colorectal carcinogenesis.

PMID- 22371808
TI  - Analysis of demographic and clinical factors affecting the outcome of radioiodine
      therapy in patients with hyperthyroidism.
AB  - INTRODUCTION: The influence of demographic and clinical factors on the outcome of
      (131)I therapy in hyperthyroid patients has been examined, based on a
      retrospective evaluation of results obtained in patients submitted to (131)I
      treatment at the Department of Nuclear Medicine and Oncological Endocrinology,
      Medical University of Lodz (Province Hospital, Zgierz). The goal of the study was
      to analyse such factors as the age and sex of patients, disease duration, as well
      as the hormonal status before (131)I application, which could have an influence
      on the effects of therapy with radioiodine (131)I. MATERIAL AND METHODS: The
      study involved 500 randomly selected patients with hyperthyroidism, treated with
      (131)I radioiodine. The following 3 groups were defined: group 1 - patients with
      multinodular goitre (MNG), n = 200; group 2 - patients with a single autonomous
      nodule of the thyroid (AFTN), n = 100; group 3 - patients with Graves' disease
      (GD), n = 200. The local ethics committee (in the Polish Mother's Memorial
      Hospital - Research Institute, Lodz) approved the study. RESULTS: The obtained
      results indicate that the efficacy of therapy with (131)I applied in patients
      with MNG, AFTN and GD does not depend on either patient sex or patient age. The
      length of antithyroid treatment before (131)I therapy onset does not appear to
      have any effect on the therapy outcome, and the baseline thyrotropin
      concentration seems to be significant only in the case of GD. CONCLUSIONS: The
      analysed demographic factors do not affect the outcome of (131)I therapy in
      hyperthyroidism.

PMID- 22371809
TI  - Effect of ligamenta flava hypertrophy on lumbar disc herniation with
      contralateral symptoms and signs: a clinical and morphometric study.
AB  - INTRODUCTION: The purpose of this study was to determine whether ligamentum
      flavum hypertrophy among disc herniated patients causes contralateral pain
      symptoms. For this reason we measured the thickness of the ligament in disc
      herniated patients with ipsilateral or contralateral symptoms. MATERIAL AND
      METHODS: Two hundred disc herniated patients with ipsilateral symptoms as group I
      were compared with five disc herniated patients with only contralateral symptoms
      as group II. Ligamenta flava thicknesses and spinal canal diameters of both
      groups were measured on magnetic resonance imaging (MRI) with a micro-caliper.
      RESULTS: Both groups underwent surgery only on the disc herniated side. The total
      thicknesses of the ligamenta flava in group II was thicker than in group I. There
      was no spinal stenosis in either group and no significance difference between the
      groups. Statistically significant differences were found for both ipsilateral and
      contralateral thickness of the ligament flava in both groups. We also compared
      thickness of the ligamenta flava for each level of disc herniation in group I;
      ligamenta flava hypertrophy was more common at L3-L4 and L4-L5 levels of
      vertebrae in females. CONCLUSIONS: Aetiology of contralateral sciatica among disc
      herniated patients may be related to hypertrophy of the ligamenta flava,
      especially on the opposite side. Surgical approaches of the disc herniated side
      alone may be sufficient for a good outcome.

PMID- 22371810
TI  - Videolaryngoscopic and videostroboscopic evaluation following laser CO(2) and
      conventional cordectomy of T(is) and T(1) glottic carcinoma.
AB  - INTRODUCTION: This paper is an analysis of long-term functional results, observed
      on videolaryngoscopic and videostroboscopic examination, of two different types
      of surgical intervention for T(is) and T(1) glottic carcinoma: laryngofissure
      conventional cordectomy and endoscopic laser CO(2) cordectomy, with or without
      additional radiation therapy (using (60)Co). MATERIAL AND METHODS: A total of 46
      patients with T(is) and T(1) glottic carcinoma, 43 men (93.48%) and 3 women
      (6.52%), served as subjects. All were treated surgically with laryngofissure
      conventional cordectomy (15 patients, 32.61%) or endoscopic laser CO(2)
      cordectomy (31 patients, 67.39%). The procedures were performed in the Department
      of Otolaryngology at the Medical University of Warsaw between November 1990 and
      February 2004. Videolaryngoscopic and videostroboscopic examinations were
      conducted a minimum of 3 years after the surgery, between January 2006 and
      February 2007. The appearance of the neocord (the scar after cordectomy), scar or
      synechia formation in the anterior commissure, movements of the vocal folds on
      respiration and phonation, difference in level between the neocord and the normal
      vocal fold, glottic closure, phonation type, and ventricular folds hyperfunction
      were examined. The symmetry of vocal fold vibrations, regularity of vibrations,
      glottic closure, amplitude of vibrations, and mucosal wave were also evaluated.
      RESULTS: IN OUR STUDY, THE VIDEOLARYNGOSCOPIC AND VIDEOLARYNGOSTROBOSCOPIC
      EXAMINATION SHOWED A SIGNIFICANTLY HIGHER OCCURRENCE OF THE FOLLOWING FINDINGS IN
      PATIENTS AFTER ENDOSCOPIC LASER CORDECTOMY: phonation at the glottic level,
      complete glottic closure, and a tendency to vibration of the neocord on
      phonation. CONCLUSIONS: Ventricular hyperfunction on phonation and scar or
      synechia formation in the anterior commissure were observed statistically more
      frequently in patients after laryngofissure conventional cordectomy.

PMID- 22371811
TI  - Immune-complex deposits in "pauci-immune" glomerulonephritis: a case report and
      brief review of recent literature.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is
      considered a "pauci-immune" disease, characterized by absent or mild glomerular
      tuft staining for immunoglobulin and/or complement. We describe a 72-year-old man
      with progressive renal failure over five months who was found to have P-ANCA
      associated crescentic glomerulonephritis. Renal biopsy also revealed
      immunofluorescence staining for Immunoglobulin G and C3. Treatment comprised
      corticosteroids, cyclophosphamide, and plasmapheresis but unfortunately kidney
      function did not recover, likely due to substantial interstitial fibrosis at
      diagnosis. This case illustrates that serologic evaluation for ANCAs should not
      be discounted when immune deposits are present. Prompt diagnosis is warranted.

PMID- 22371812
TI  - Antonovsky's Sense of Coherence Scale: Cultural Validation of Soc Questionnaire
      and Socio-Demographic Patterns in an Italian Population.
AB  - BACKGROUND: The theory of salutogenesis entails that the ability to use resources
      for one's wellbeing is more important than the resources themselves. This ability
      is referred to as the Sense of Coherence (SOC). This paper present the cross
      culturally adapted version of the Italian questionnaire (13 items), and the
      psychometric and statistical testing of the SOC properties. It offers for the
      first time a view of the distribution of SOC in an Italian sample, and uses a
      multivariate method to clarify the effects of socio-demographic determinants on
      SOC. METHODS: The cross-cultural adaptation of the English SOC questionnaire was
      carried out according to the guidelines reported in literature. To evaluate the
      psychometric and statistical properties we assessed reliability, validity and
      frequency distribution of the collected data. A Generalised Linear Model was used
      to analyse the effects of socio demographic variables on SOC. RESULTS: The
      Italian SOC scale demonstrates a good internal consistency (alpha = 0.825). The
      model obtained with factorial analysis is not related to the traditional
      dimensions of SOC represented in more than one factor. The multivariate analysis
      highlights the joint influence of gender, age and education on SOC. CONCLUSION:
      The validated Italian questionnaire is now available. Socio-demographic variables
      should be taken into account as confounders when SOC values among different
      populations are compared. Presenting data on SOC of the Italian population makes
      a control population available for comparisons with specific subgroups, such as
      patient populations. Now, the Italian challenge is to integrate the salutogenic
      approach into Public Health police.

PMID- 22371813
TI  - Magical attachment: Children in magical relations with hospital clowns.
AB  - The aim of the present study was to achieve a theoretical understanding of
      several different-age children's experiences of magic relations with hospital
      clowns in the context of medical care, and to do so using psychological theory
      and a child perspective. The method used was qualitative and focused on nine
      children. The results showed that age was important to consider in better
      understanding how the children experienced the relation with the hospital clowns,
      how they described the magical aspects of the encounter and how they viewed the
      importance of clown encounters to their own well-being. The present theoretical
      interpretation characterized the encounter with hospital clowns as a magical safe
      area, an intermediate area between fantasy and reality. The discussion presented
      a line of reasoning concerning a magical attachment between the child and the
      hospital clowns, stating that this attachment: a) comprised a temporary relation;
      b) gave anonymity; c) entailed reversed roles; and d) created an emotional
      experience of boundary-transcending opportunities.

PMID- 22371814
TI  - Simultaneous comparison of many triphasic defibrillation waveforms.
AB  - Biphasic defibrillation waveforms are now accepted as being more effective at
      terminating ventricular fibrillation (VF) than monophasic waveforms. If two
      phases are better than one, this naturally leads to the hypothesis that
      additional phases improve efficacy. This study tests the hypothesis by adding one
      additional phase. We examined the efficacy of 18 different triphasic waveforms
      simultaneously.We tested the rate of recovery, i.e., successful defibrillation,
      of 21 guinea pigs (820-1,050 g) using triphasic, monophasic and biphasic
      defibrillation waveforms. The biphasic and monophasic were control waveforms. VF
      was electrically induced twenty times per animal and a single defibrillation
      attempt was made using a test waveform VF episode. Every waveform was adjusted to
      the energy required to defibrillate that animal 50% of the time, using a biphasic
      waveform as a control. The success rate of each triphasic waveform was pair-wise
      compared to the biphasic and monophasic control using the adjusted McNemar
      statistical test.Of the 18 triphasic waveforms tested, two were significantly
      poorer than the monophasic control (p<0.05). One was superior to the biphasic
      waveform (p<0.1), but not statistically so. We concluded that, while adding a
      phase to a monophasic waveform does improve efficacy, adding an additional phase
      to a biphasic waveform does not necessarily improve efficacy.

PMID- 22371815
TI  - The use of a disclosing agent during resective periodontal surgery for improved
      removal of biofilm.
AB  - A total removal of the bacterial deposits is one of the main challenges of
      periodontal therapy. A surgical approach is sometimes required in order to allow
      a correct access to the areas not thoroughly reached during the initial therapy.
      The present study focuses on the surgical scaling effectiveness in root deposits
      removal; the potential support of a disclosing agent during this procedure is
      also evaluated. Forty surgical periodontal patients were randomly divided between
      surgeries where the operator was informed about a final examination of the
      residual root deposits and surgeries where the operator was not informed.
      Straight after scaling procedures a supervisor recorded the O'Leary Plaque Index
      of the exposed roots by mean of a disclosing agent and the percentage of teeth
      with residual biofilm. After the stained deposits removal, a second chromatic
      examination was performed and new data were collected. Mann-Whitney U-test and
      Wilcoxon test for paired samples were used for comparisons respectively between
      the two surgery groups and the first and the second chromatic examination; one
      sided p-value was set at 0.05. At first examination no significant differences
      between the two groups were observed regarding Plaque Index (p=0.24) and
      percentages of teeth with residual biofilm (p=0.07). The 100% removal of roots
      deposits was never achieved during the study but a significant reduction of 80%
      of root deposits was observed between first and second examination (p=0.0001).
      Since root deposits removal during periodontal surgery resulted always
      suboptimal, the use of a disclosing agent during this procedure could be a useful
      and practical aid.

PMID- 22371817
TI  - Characterization of Vibrio cholerae O139 of an Aquatic Isolate in Northern
      Vietnam.
AB  - During the cholera survey in Namdinh province (northern Vietnam) in July, 2010,
      one strain of Vibrio cholerae O139 was isolated from 7 environmental water
      samples positive for ctxA, toxR,VCO139 genes and named as V. cholerae O139, ND1
      strain. This strain was lysogenic harbouring a genome similar to the filamentous
      phage fs1. The replicative form DNA of this phage (named as ND1-fs1, 6856 bp) was
      sequenced and compared with the other filamentous phages. The filamentous phage
      ND1-fs1 integrates into the region between ctxB and rtxA genes. The genetic
      organization of the CTXphi of V. cholerae O139, strain ND1 was determined and the
      schematic representation of the genetic organization was shown together with the
      ND1-fs1 prophage.

PMID- 22371816
TI  - Genomic Comparison of the Closely Related Salmonella enterica Serovars
      Enteritidis and Dublin.
AB  - The Enteritidis and Dublin serovars of Salmonella enterica are closely related,
      yet they differ significantly in pathogenicity and epidemiology. S. Enteritidis
      is a broad host range serovar that commonly causes gastroenteritis and
      infrequently causes invasive disease in humans. S. Dublin mainly colonizes cattle
      but upon infecting humans often results in invasive disease.To gain a broader
      view of the extent of these differences we conducted microarray-based comparative
      genomics between several field isolates from each serovar. Genome degradation has
      been correlated with host adaptation in Salmonella, thus we also compared at
      whole genome scale the available genomic sequences of them to evaluate pseudogene
      composition within each serovar.Microarray analysis revealed 3771 CDS shared by
      both serovars while 33 were only present in Enteritidis and 87 were exclusive to
      Dublin. Pseudogene evaluation showed 177 inactive CDS in S. Dublin which
      correspond to active genes in S. Enteritidis, nine of which are also inactive in
      the host adapted S. Gallinarum and S. Choleraesuis serovars. Sequencing of these
      9 CDS in several S. Dublin clinical isolates revealed that they are pseudogenes
      in all of them, indicating that this feature is not peculiar to the sequenced
      strain. Among these CDS, shdA (Peyer's patch colonization factor) and mglA
      (galactoside transport ATP binding protein), appear also to be inactive in the
      human adapted S. Typhi and S. Paratyphi A, suggesting that functionality of these
      genes may be relevant for the capacity of certain Salmonella serovars to infect a
      broad range of hosts.

PMID- 22371818
TI  - A rare periosteal diaphyseal lesion of the ulna.
AB  - Periosteal lesions of the ulna diaphysis are rare, include a wide spectrum of
      tumors, and may cause considerable diagnostic problems. Surgical treatment may
      vary widely, based on an accurate diagnosis. We present the case of a periosteal,
      extraskeletal low grade myxoid chondrosarcoma of the ulna diaphysis. The surgical
      therapy included an en-bloc resection with allograft reconstruction. The patient
      showed a favorable outcome. Careful preoperative evaluation and planning are
      imperative to obtain a satisfactory oncological and functional outcome,
      especially with uncommon tumor presentations at rare locations.

PMID- 22371819
TI  - A Methodological Description of a Randomised Controlled Trial Comparing Hospital
      Based Care and Hospital-Based Home Care when a Child is Newly Diagnosed with Type
      1 Diabetes.
AB  - AIM AND OBJECTIVE: To describe the study design of a randomised controlled trial
      with the aim of comparing two different regimes for children with newly diagnosed
      type 1 diabetes; hospital-based care and hospital-based home care. BACKGROUND:
      Procedures for hospital admission and sojourn in connection with diagnose vary
      greatly worldwide and the existing evidence is insufficient to allow for any
      conclusive determination of whether hospital-based or home-based care is the best
      alternative for most families. Comparative studies with adequate power and
      outcome measurements, as well as measurements of cost-effectiveness are needed.
      DESIGN: The study design was based on the Medical Research Council framework for
      complex interventions. After two to three days with hospital-based care, children
      between the ages of 3 and 16 were randomised to receive either continued hospital
      based care for a total of 1-2 weeks or hospital-based home care, which refers to
      specialist care in a home-based setting. The trial started in March 2008 at a
      University Hospital in Sweden and was closed in September 2011 when a sufficient
      number of children according to power calculation, were included. The primary
      outcome was the child's metabolic control during the following two years.
      Secondary outcomes were set to evaluate the family and child situation as well as
      the organisation of care. DISCUSSION: Childhood diabetes requires families and
      children to learn to perform multiple daily tasks. Even though intervention in
      health care is complex with several interacting components entailing practical
      and methodological difficulties, there is nonetheless, a need for randomised
      controlled trials in order to evaluate and develop better systems for the
      learning processes of families that can lead to long-term improvement in
      adherence and outcome. TRIAL REGISTRATION: Trial Register NCT00804232.

PMID- 22371820
TI  - Living in the presence of death: an integrative literature review of relatives'
      important existential concerns when caring for a severely ill family member.
AB  - AIM: The aim of this study was to explore relatives' existential concerns when
      caring for a seriously ill family member as well as to describe interventions
      that meet these concerns. METHODS: In this integrative literature review we
      assessed and classified 17 papers, 12 qualitative and 5 quantitative. Literature
      was sought in the databases Cinahl, PubMed, Psykinfo and Web of Science in
      September 2009 and in March 2010. Search terms used in different combinations
      were: family, family caregiver, next of kin, relatives, palliative, palliative
      care, end-of-life care, existential, spirit*. Data were redrawn from the papers
      results/findings, and synthesized into a new descriptive content. RESULTS: The
      results were categorized from 13 papers exploring relatives' important
      existential concerns and 4 papers describing interventions aimed to support them
      in the existential area. A majority of the reviewed papers had been written in
      Sweden and concerned relatives of patients with cancer. One overarching theme,
      living in the presence of death, and three categories: responses to life close to
      death; support when death is near; and beyond the presence of death were created.
      CONCLUSION: There is an urgent demand for large-scale studies using accurate
      methodology, as well as a need to design qualified investigations regarding the
      effects of various interventions, and to determine which interventions are the
      most effective in supporting relatives who experience existential distress
      manifested physically and/or psychologically. There is also a considerable demand
      for educational interventions among professionals in various healthcare settings
      to increase their knowledge regarding existential concerns among relatives.

PMID- 22371821
TI  - Posterior reversible encephalopathy syndrome mimicking a left middle cerebral
      artery stroke.
AB  - Certain Acute Clinical presentations are highly suggestive of stroke caused by
      specific mechanisms. One example of this would be the sudden onset of aphasia
      without hemiparesis often reflecting cerebral embolism, frequently from a cardiac
      source. Posterior reversible encephalopathy syndrome (PRES) describes a usually
      reversible neurologic syndrome with a variety of presenting symptoms from
      headache, altered mental status, seizures, vomiting, diminished spontaneity and
      speech, abnormalities of visual perception and visual loss. We report a patient
      presenting with elevated blood pressure, CT characteristics of PRES but a highly
      circumscribed neurologic syndrome (Wernicke's Aphasia without hemiparesis)
      suggestive of a cardioembolic stroke affecting the left MCA territory. That is,
      PRES mimicked a focal stroke syndrome. The importance of recognizing this
      possibility is that his deficits resolved with blood pressure control, while
      other treatments, such as intensifying his anticoagulation would have been
      inappropriate. In addition, allowing his blood pressure to remain elevated as is
      often done in the setting of an acute stroke might have perpetuated the
      underlying pathophysiology of PRES leading to a worse clinical outcome. For this
      reason PRES needs to be recognized quickly and treated appropriately.

PMID- 22371822
TI  - Genetic structure, nestmate recognition and behaviour of two cryptic species of
      the invasive big-headed ant Pheidole megacephala.
AB  - BACKGROUND: Biological invasions are recognized as a major cause of biodiversity
      decline and have considerable impact on the economy and human health. The African
      big-headed ant Pheidole megacephala is considered one of the world's most harmful
      invasive species. METHODOLOGY/PRINCIPAL FINDINGS: To better understand its
      ecological and demographic features, we combined behavioural (aggression tests),
      chemical (quantitative and qualitative analyses of cuticular lipids) and genetic
      (mitochondrial divergence and polymorphism of DNA microsatellite markers) data
      obtained for eight populations in Cameroon. Molecular data revealed two cryptic
      species of P. megacephala, one inhabiting urban areas and the other rainforests.
      Urban populations belong to the same phylogenetic group than those introduced in
      Australia and in other parts of the world. Behavioural analyses show that the
      eight populations sampled make up four mutually aggressive supercolonies. The
      maximum distance between nests from the same supercolony was 49 km and the
      closest distance between two nests belonging to two different supercolonies was
      46 m. The genetic data and chemical analyses confirmed the behavioural tests as
      all of the nests were correctly assigned to their supercolony. Genetic diversity
      appears significantly greater in Africa than in introduced populations in
      Australia; by contrast, urban and Australian populations are characterized by a
      higher chemical diversity than rainforest ones. CONCLUSIONS/SIGNIFICANCE:
      Overall, our study shows that populations of P. megacephala in Cameroon adopt a
      unicolonial social structure, like invasive populations in Australia. However,
      the size of the supercolonies appears several orders of magnitude smaller in
      Africa. This implies competition between African supercolonies and explains why
      they persist over evolutionary time scales.

PMID- 22371823
TI  - Knowledge acquisition, semantic text mining, and security risks in health and
      biomedical informatics.
AB  - Computational techniques have been adopted in medical and biological systems for
      a long time. There is no doubt that the development and application of
      computational methods will render great help in better understanding biomedical
      and biological functions. Large amounts of datasets have been produced by
      biomedical and biological experiments and simulations. In order for researchers
      to gain knowledge from original data, nontrivial transformation is necessary,
      which is regarded as a critical link in the chain of knowledge acquisition,
      sharing, and reuse. Challenges that have been encountered include: how to
      efficiently and effectively represent human knowledge in formal computing models,
      how to take advantage of semantic text mining techniques rather than traditional
      syntactic text mining, and how to handle security issues during the knowledge
      sharing and reuse. This paper summarizes the state-of-the-art in these research
      directions. We aim to provide readers with an introduction of major computing
      themes to be applied to the medical and biological research.

PMID- 22371824
TI  - Modulation of heat shock protein response in SH-SY5Y by mobile phone microwaves.
AB  - AIM: To investigate putative biological damage caused by GSM mobile phone
      frequencies by assessing electromagnetic fields during mobile phone working.
      METHODS: Neuron-like cells, obtained by retinoic-acid-induced differentiation of
      human neuroblastoma SH-SY5Y cells, were exposed for 2 h and 4 h to microwaves at
      1800 MHz frequency bands. RESULTS: Cell stress response was evaluated by MTT
      assay as well as changes in the heat shock protein expression (Hsp20, Hsp27 and
      Hsp70) and caspase-3 activity levels, as biomarkers of apoptotic pathway. Under
      our experimental conditions, neither cell viability nor Hsp27 expression nor
      caspase-3 activity was significantly changed. Interestingly, a significant
      decrease in Hsp20 expression was observed at both times of exposure, whereas
      Hsp70 levels were significantly increased only after 4 h exposure. CONCLUSION:
      The modulation of the expression of Hsps in neuronal cells can be an early
      response to radiofrequency microwaves.

PMID- 22371825
TI  - Optoelectronic reservoir computing.
AB  - Reservoir computing is a recently introduced, highly efficient bio-inspired
      approach for processing time dependent data. The basic scheme of reservoir
      computing consists of a non linear recurrent dynamical system coupled to a single
      input layer and a single output layer. Within these constraints many
      implementations are possible. Here we report an optoelectronic implementation of
      reservoir computing based on a recently proposed architecture consisting of a
      single non linear node and a delay line. Our implementation is sufficiently fast
      for real time information processing. We illustrate its performance on tasks of
      practical importance such as nonlinear channel equalization and speech
      recognition, and obtain results comparable to state of the art digital
      implementations.

PMID- 22371826
TI  - Cholinergic and non-cholinergic functions of two acetylcholinesterase genes
      revealed by gene-silencing in Tribolium castaneum.
AB  - We compared biological functions of two acetylcholinesterase genes (TcAce1 and
      TcAce2) in Tribolium castaneum, a globally distributed major pest of stored grain
      products and an emerging model organism, by using RNA interference. Although both
      genes expressed at all developmental stages and mainly in the brain, the
      transcript level of TcAce1 was 1.2- to 8.7-fold higher than that of TcAce2,
      depending on developmental stages. Silencing TcAce1 in 20-day larvae led to 100%
      mortality within two weeks after eclosion and increased larval susceptibilities
      to anticholinesterase insecticides. In contrast, silencing TcAce2 did not show
      insect mortality and significantly affect insecticide susceptibility, but delayed
      insect development and reduced female egg-laying and egg hatching. These results
      demonstrate for the first time that TcAce1 plays a major role in cholinergic
      functions and is the target of anticholinesterase insecticides, whereas TcAce2
      plays an important, non-cholinergic role in female reproduction, embryo
      development, and growth of offspring.

PMID- 22371827
TI  - On prosthodontic interfaces: a continuing narrative.

PMID- 22371828
TI  - An interview with Dr Lyndon Cooper.

PMID- 22371829
TI  - The association of denture stomatitis and partial removable dental prostheses: a
      systematic review.
AB  - PURPOSE: The aim of this systematic review was to analyze the evidence on the
      occurrence of denture stomatitis (DS) and potential risk factors in patients
      wearing partial removable dental prostheses (RDPs). MATERIALS AND METHODS:
      MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the
      Cochrane Database of Systematic Reviews were searched and complemented by manual
      searching. Outcome measures were the presence of DS in patients wearing partial
      RDPs and an assessment of associated risk factors. All types of experimental and
      observational studies investigating an association between DS and the wearing of
      partial RDPs were included. Methodologic quality and level of evidence were
      assessed using valid scales. Two authors performed study selection, data
      extraction, and quality assessment independently. RESULTS: A total of eight
      studies met the inclusion criteria. The prevalence of DS in partial RDP wearers
      ranged from 1.1% to 36.7%. Data on the potential risk factors were not
      consistent. Despite the heterogeneity and methodologic quality of included
      studies, an association between DS and the wearing of partial RDPs was found.
      CONCLUSIONS: There is some evidence that the presence of DS is associated with
      the wearing of partial RDPs. However, because of methodologic limitations and
      cross-sectional designs of research studies, no cause-effect relationship could
      be inferred. Future research should provide higher levels of evidence to confirm
      the etiology of DS in partial RDP wearers.

PMID- 22371830
TI  - Sensitivity of magnetic resonance imaging and computed axiography in the
      diagnosis of temporomandibular joint disorders in a selected patient population.
AB  - PURPOSE: The aim of this study was to compare sensitivity differences and
      interpretative agreement for magnetic resonance imaging (MRI) and computed
      axiography (CA) tracings in a patient population group with temporomandibular
      disorder (TMD). MATERIALS AND METHODS: A convenience sample of 173 patients (53
      men, 120 women; mean age: 33.2 +/- 2.6 years) diagnosed with TMD was selected for
      this study. Each patient underwent an evaluation as per the European Academy of
      Craniomandibular Disorders clinical form as well as MRI and CA. RESULTS: Use of
      the MRI results as the gold standard for the planned comparison led to the
      following observations: a CA sensitivity of 68% for joints without morphologic
      changes (so-called normal temporomandibular joints [TMJs]), sensitivity of 27%
      for those with disc displacement, and sensitivity of 8% for those with
      osteoarthritis. The kappa index, or agreement between the two examination
      methods, was weak for normal TMJs (0.16), acceptable for anterior disc
      displacement with reduction (0.28), little for anterior disc displacement without
      reduction (0.10), and very little for morphologic alterations (0.01). CONCLUSION:
      The sensitivity and agreement of the two examination methods was generally low.
      It was even worse when pathologic changes in the TMJ were more severe. MRI and CA
      are different examinations that could both be considered for severe TMD
      diagnosis.

PMID- 22371831
TI  - Candida albicans isolation from buccal mucosa of patients with HIV wearing
      removable dental prostheses.
AB  - PURPOSE: The aim of this study was to evaluate the influence of complete or
      partial removable dental prostheses (RDPs) on the frequency of Candida albicans
      isolated from the mouth and the presence of oral candidiasis in human
      immunodeficiency virus-positive (HIV+) patients correlated with CD4 levels.
      MATERIALS AND METHODS: One hundred ninety-three HIV+ patients were evaluated; 68
      had RDPs and 125 did not. CD4 cell count was obtained after blood sampling and
      performed on the day of clinical examination. The material was collected from the
      buccal mucosa for isolation of yeasts with a sterile swab and seeded onto
      Sabouraud dextrose agar with chloramphenicol. C albicans strains were identified
      by testing germ tubes and chlamydospore formation and biochemical (zymogram,
      auxanogram) characteristics. The results were subjected to the Fischer exact test
      and chi-square tests. RESULTS: C albicans were isolated from 45 (66.17%) patients
      who had RDPs and 48 (38.4%) who did not (P = .0003). The presence of oral
      candidiasis was observed in 14 patients (7.25%), and 10 of the 14 (71.43%) were
      RDP users. The absence of candidiasis occurred in 121 (67.59%) nonusers and 58
      (32.40%) users of RDPs (P = .0065). The mean CD4 cell count was lower in patients
      with oral candidiasis regardless of the use of RDPs. CONCLUSION: The use of RDPs
      was an important factor in the isolation of C albicans among HIV+ patients, and
      CD4 level seems to play a role in the presence of oral candidiasis.

PMID- 22371832
TI  - On novel options for oromaxillofacial functional restoration.

PMID- 22371833
TI  - Masticatory performance and mandibular movement patterns of patients with natural
      dentitions, complete dentures, and implant-supported overdentures.
AB  - The aim of this study was to compare quantitatively the masticatory performance
      of patients with overdentures supported by two implants, conventional complete
      dentures, and natural dentitions. Each patient was asked to chew a gelatin cube.
      The collected remains of the test food (gelatine cube) were fractioned by a
      sieving procedure and weighed. Maximum mouth opening and masticatory area were
      measured using kinesiography. There were statistically significant differences
      among groups with respect to masticatory performance using a 3.15-mm-diameter
      sieve (P < .001) and 0.5-mm-diameter sieve (P < .001), masticatory area (P =
      .019), and maximum mouth opening (P < .001). Increasing retention of a mandibular
      complete denture with two implants improved masticatory performance.

PMID- 22371834
TI  - Clinical performance of cast clasp-retained removable partial dentures: a
      retrospective study.
AB  - PURPOSE: This retrospective study investigated the survival rate of 174 clasp
      retained removable partial dentures (CR-RPDs) made at the Department of
      Prosthodontics of the Regensburg University Medical Center over a 25-year period
      (1984 to 2009). MATERIALS AND METHODS: The study analyzed the frequency of and
      time to the fracture of clasps, connectors, or denture bases; the occurrence of
      caries or periodontal lesions; the loss of abutment teeth; and the necessity of
      maintenance procedures such as relining or treatment of pressure areas. RESULTS:
      The median follow-up time of 3 years was calculated using the inverse Kaplan
      Meier method. The 5-year survival rate (time to renewal) of all CR-RPDs was
      96.4%; the 10-year survival rate was 89.8%. Fractures most frequently occurred in
      clasps (n = 28, 16.1%) followed by major connectors (n = 9, 5.1%) and minor
      connectors (n = 6, 3.4%). The 5-year event-free rate for clasp fracture was
      80.4%; the 10-year event-free rate was 76.9%. Caries lesions on abutment teeth
      were seen in 31.6% of patients, and 35.6% showed inflammation of the periodontal
      tissue surrounding the abutment teeth. The 5-year event-free rate for caries was
      58.4%; the 10-year rate was 39.6%. A frequent complication was loss of abutment
      teeth (n = 15), but this complication was not age-dependent. After insertion of
      their prostheses, one-third of patients (n = 53, 30.5%) showed pressure areas of
      the mucosa. Significantly more (P < .001) pressure areas were caused by
      prostheses of the mandible (39.6%) than by those of the maxilla (12.5%).
      CONCLUSIONS: CR-RPDs showed a survival rate of approximately 90% after 10 years
      of oral service. The predominant complications during oral service were caries
      lesions, loss of abutment teeth, and fracture of clasps.

PMID- 22371835
TI  - Patients' profiles and perceptions of complete dentures in a university dental
      clinic.
AB  - This study investigated factors associated with perceptions of complete dentures
      (CDs) among patients presenting at a university dental clinic. A retrospective
      chart review of all new edentulous patients presenting at the Athens University
      School of Dentistry Removable Prosthodontics Clinic between 1993 and 2002 (n =
      2,526) was completed. More than half of CD-wearing patients were dissatisfied
      with their dentures at the initial visit. Dissatisfaction was correlated with
      current use of denture adhesives and less time spent edentulous and was more
      prevalent among females. Factors affecting patients? adaptation to and
      satisfaction with CDs should be considered at CD fabrication and follow-up.

PMID- 22371836
TI  - Prosthetic aspects and patient satisfaction with resilient liner and clip
      attachments for bar- and implant-retained mandibular overdentures: a 3-year
      randomized clinical study.
AB  - PURPOSE: This report aimed to compare prosthetic aspects and patient satisfaction
      during a 3-year randomized clinical trial of bar- and implant-retained mandibular
      overdentures attached with either resilient liners or clips. MATERIALS AND
      METHODS: Thirty edentulous male patients (mean age: 62.5 years) received two
      implants in the anterior mandible after being allocated into two equal groups
      (according to attachment type received) using balanced randomization. After 3
      months, implants were connected with resilient bars. New maxillary complete
      dentures were then constructed, and mandibular overdentures were retained to the
      bars with either clips (group I) or silicone resilient liners (group II).
      Subjects indicated satisfaction with their prostheses using a questionnaire and
      visual analog scale. Patient satisfaction and prosthetic complications were
      recorded for both attachments at 6 months and 1 and 3 years after overdenture
      insertion. RESULTS: Comfort and stability with the maxillary denture and ease of
      hygiene procedures were rated higher in group II, while ease of handling the
      dentures was rated higher in group I. No significant differences in other
      parameters of patient satisfaction between groups were noted after 3 years. The
      mean number of prosthetic adjustments and repairs in group I (11.9) was
      significantly higher (P = .00) compared to that in group II (4.8). The most
      common complication in group I was clip wear, while separation of the resilient
      liner from the denture base was the most common problem in group II. Hyperplasia
      under the bar and flabby ridge in the maxilla occurred significantly more often
      in group I compared to group II. CONCLUSIONS: Resilient liner-retained mandibular
      overdentures had comparable patient satisfaction, less prosthetic maintenance and
      costs, and less soft tissue complications when compared to clip-retained ones
      after 3 years.

PMID- 22371837
TI  - Trial of experimental toothpastes regarding quality for cleaning dentures.
AB  - The aim of this study was to evaluate the efficacy of experimental toothpastes
      for removing denture biofilm by means of a randomized crossover trial. Thirty
      volunteers brushed their dentures using a brush and four pastes: (1) Corega
      refreshing mint (control), (2) 0.2% chloramine T, (3) 1.0% chloramine T, and (4)
      0.01% fluorosurfactant. Each paste was used for 7 days, and participants were
      randomized to use them according to one of four sequences. Biofilm was disclosed
      (neutral red) after each period, photographed, and quantified by means of a
      software program. All experimental toothpastes were similar to the control in
      terms of posttreatment biofilm coverage.

PMID- 22371838
TI  - A comparison of three methods to evaluate the position of an artificial ear on
      the deficient side of the face from a three-dimensional surface scan of patients
      with hemifacial microsomia.
AB  - PURPOSE: Patients with hemifacial microsomia may have a missing ear on the
      deficient side of the face. The fabrication of an ear for such individuals
      usually has been accomplished by directly measuring the ear on the normal side to
      construct a prosthesis based on these dimensions, and the positioning has been,
      to a large extent, primarily operator-dependent. The aim of the present study was
      to compare three methods, developed from the identification of landmarks plotted
      on three-dimensional surface scans, to evaluate the position of an artificial ear
      on the deficient side of the face compared with the position of the natural ear
      on the normally developed side. MATERIALS AND METHODS: Laser scans were
      undertaken of the faces of 14 subjects with hemifacial microsomia. Landmarks on
      the ear and face on the normal side were identified. Three methods of mirroring
      the normal ear on the deficient side of the face were investigated, which used
      either facial landmarks from the orbital area or a zero reference point generated
      from the intersection of three orthogonal planes on a frame of reference. To
      assess the methods, landmarks were identified on the ear situated on the normal
      side as well as on the face. These landmarks yielded paired dimensional
      measurements that could be compared between the normal and deficient sides. Mean
      differences and 95% confidence intervals were calculated. RESULTS: It was
      possible to mirror the normal ear image on to the deficient side of the face
      using all three methods. Generally only small differences between the dimensional
      measurements on the normal and deficient sides were observed. However, two-way
      analysis of variance revealed statistically significant differences between the
      three methods (P = .005). CONCLUSIONS: The method of mirroring using the outer
      canthi was found to result in the smallest dimensional differences between the
      anthropometric points on the ear and face between the normally developed and
      deficient sides. However, the effects of the deformity can result in limitations
      in relation to achieving a precise alignment of the ear to the facial tissues.
      This requires further study.

PMID- 22371839
TI  - Strain development of screw-retained implant-supported fixed restorations:
      procera implant bridge versus conventionally cast restorations.
AB  - The aim of this study was to quantify the strain development of screw-retained
      three-unit implant-supported Procera Implant Bridge restorations. Two groups of
      screw-retained implant-supported restorations (n = 10) were fabricated by means
      of casting or computer-aided design/computer-assisted manufacture (CAD/CAM) to
      fit an in vitro cast situation with two implants. During fixation of the
      restorations, the emerging strains were recorded using strain gauges attached to
      the cast material mesially and distally adjacent to the implants. Absolute mean
      strain development ranged from 29.35 MUm/m to 2,665.80 MUm/m at the different
      strain gauge locations. Fabrication method had a significant effect on strain
      development (multivariate analysis of variance, P = .000), with the cast
      restorations showing significantly higher strain levels compared to the CAD/CAM
      fabricated superstructures. CAD/CAM fabrication of screw-retained implant
      supported restorations provides greater passivity of fit compared to conventional
      fabrication methods such as casting.

PMID- 22371840
TI  - X-ray microtomographic evaluation of the influence of two preparation types on
      marginal fit of CAD/CAM alumina copings: a pilot study.
AB  - This study evaluated the influence of two preparation types on the marginal fit
      of computer-aided design/computer-assisted manufacture (CAD/CAM) alumina copings.
      Two subgroups of four alumina copings each were fabricated using alumina master
      dies with either a chamfer or 90-degree shoulder preparation. Copings were
      scanned with an x-ray microtomographic scanner, and marginal fit was evaluated.
      The preparation types presented no statistically significant differences
      regarding marginal gap (P = .410) and absolute marginal discrepancy (P = .229).
      No correlation was found between marginal fit of CAD/CAM alumina copings and
      preparation type. Marginal fit could be considered within the limits of clinical
      acceptance.

PMID- 22371841
TI  - Tooth loss and oral rehabilitation in Greek middle-aged adults and senior
      citizens.
AB  - PURPOSE: The aims of this study were to investigate the prevalence of tooth loss
      in Greek individuals aged 35 to 44 and 65 to 74 years in relation to
      sociodemographic parameters and to describe their prosthetic status and needs.
      MATERIALS AND METHODS: A stratified cluster sample of 1,188 middle-aged adults
      and 1,093 senior citizens was selected according to World Health Organization
      (WHO) guidelines for national pathfinder surveys. Tooth loss and prosthetic
      status and needs were recorded according to WHO criteria. Sociodemographic data
      were collected through face-to-face interviews. RESULTS: Complete edentulism
      affected 0.3% of individuals aged 35 to 44 years and 31.5% of those aged 65 to 74
      years. Most middle-aged adults (92.1%) had >= 21 natural teeth, while the
      corresponding percentage for the senior citizens was 23.1%. The mean number of
      missing teeth was 5.2 in middle-aged adults and 21.6 in senior citizens. The
      multivariate analysis showed that education level was the only predictor of tooth
      loss in both age groups. Approximately 38% of those aged 35 to 44 years and 80%
      of those aged 65 to 74 years had dental prostheses, while 47.6% of middle-aged
      adults and 66.3% of senior citizens did not need any prosthetic treatment. The
      need for complete dentures was relatively low in both age groups. Comparisons of
      the present results with those of 1985 indicate that the dentate status of Greek
      adults aged 35 to 44 years has not improved. Furthermore, the prevalence of tooth
      loss in the elderly population was high compared with internationally reported
      findings. CONCLUSION: The replacement of missing teeth with fixed or removable
      prostheses will continue to be common in Greece for the foreseeable future.

PMID- 22371842
TI  - Implantomania: prosthodontics at a crossroads.
AB  - Throughout the 1980s and '90s, a small core group of clinical scholars played a
      major and pivotal role in the combined surgical and prosthodontic dissemination
      of osseointegration scholarship. As professor of oromaxillofacial surgery at the
      University of Washington, Dr Philip Worthington was one such pioneering educator.
      His academic leadership was acknowledged via numerous academic honors and
      tributes, including his recent postretirement recognition as distinguished
      professor at his university. This invited paper is a personal assessment of the
      impact of clinical changes ushered in by the osseointegration technique and was
      recently presented at the University of Washington's unique celebratory tribute
      to Professor Worthington.

PMID- 22371843
TI  - Dendritic cells loaded with mRNA encoding full-length tumor antigens prime CD4+
      and CD8+ T cells in melanoma patients.
AB  - It is generally thought that dendritic cells (DCs) loaded with full-length tumor
      antigen could improve immunotherapy by stimulating broad T-cell responses and by
      allowing treatment irrespective of the patient's human leukocyte antigen (HLA)
      type. To investigate this, we determined the specificity of T cells from melanoma
      patients treated with DCs loaded with mRNA encoding a full-length tumor antigen
      fused to a signal peptide and an HLA class II sorting signal, allowing
      presentation in HLA class I and II. In delayed-type hypersensitive (DTH)-biopsies
      and blood, we found functional CD8(+) and CD4(+) T cells recognizing novel
      treatment-antigen-derived epitopes, presented by several HLA types. Additionally,
      we identified a CD8(+) response specific for the signal peptide incorporated to
      elicit presentation by HLA class II and a CD4(+) response specific for the fusion
      region of the signal peptide and one of the antigens. This demonstrates that the
      fusion proteins contain newly created immunogenic sequences and provides evidence
      that ex vivo-generated mRNA-modified DCs can induce effector CD8(+) and CD4(+) T
      cells from the naive T-cell repertoire of melanoma patients. Thus, this work
      provides definitive proof that DCs presenting the full antigenic spectrum of
      tumor antigens can induce T cells specific for novel epitopes and can be
      administered to patients irrespective of their HLA type.

PMID- 22371844
TI  - Advances in cell and gene-based therapies for cystic fibrosis lung disease.
AB  - Cystic fibrosis (CF) is a disease characterized by airway infection,
      inflammation, remodeling, and obstruction that gradually destroy the lungs.
      Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene to airway epithelia may offer advantages, as the tissue is accessible for
      topical delivery of vectors. Yet, physical and host immune barriers in the lung
      present challenges for successful gene transfer to the respiratory tract.
      Advances in gene transfer approaches, tissue engineering, and novel animal models
      are generating excitement within the CF research field. This review discusses
      current challenges and advancements in viral and nonviral vectors, cell-based
      therapies, and CF animal models.

PMID- 22371845
TI  - Protein-anchoring strategy for delivering acetylcholinesterase to the
      neuromuscular junction.
AB  - Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to
      the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital
      defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single
      intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to
      Colq(-/-) mice recovered motor functions, synaptic transmission, as well as the
      morphology of the NMJ. ColQ-tailed AChE was specifically anchored to NMJ and its
      amount was restored to 89% of the wild type. We next characterized the molecular
      basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be
      specifically targeted to NMJ by an in vitro overlay assay in Colq(-/-) mice
      muscle sections. We then injected AAV1-COLQ-IRES-EGFP into the left tibialis
      anterior and detected AChE in noninjected limbs. Furthermore, the in vivo
      injection of recombinant ColQ-tailed AChE protein complex into the gluteus
      maximus muscle of Colq(-/-) mice led to accumulation of AChE in noninjected
      forelimbs. We demonstrated for the first time in vivo that the ColQ protein
      contains a tissue-targeting signal that is sufficient for anchoring itself to the
      NMJ. We propose that the protein-anchoring strategy is potentially applicable to
      a broad spectrum of diseases affecting extracellular matrix molecules.

PMID- 22371846
TI  - Preclinical safety and efficacy of human CD34(+) cells transduced with lentiviral
      vector for the treatment of Wiskott-Aldrich syndrome.
AB  - Gene therapy with ex vivo-transduced hematopoietic stem/progenitor cells may
      represent a valid therapeutic option for monogenic immunohematological disorders
      such as Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency associated
      with thrombocytopenia. We evaluated the preclinical safety and efficacy of human
      CD34(+) cells transduced with lentiviral vectors (LV) encoding WAS protein
      (WASp). We first set up and validated a transduction protocol for CD34(+) cells
      derived from bone marrow (BM) or mobilized peripheral blood (MPB) using a
      clinical grade, highly purified LV. Robust transduction of progenitor cells was
      obtained in normal donors and WAS patients' cells, without evidence of toxicity.
      To study biodistribution of human cells and exclude vector release in vivo, LV
      transduced CD34(+) cells were transplanted in immunodeficient mice, showing a
      normal engraftment and differentiation ability towards transduced lymphoid and
      myeloid cells in hematopoietic tissues. Vector mobilization to host cells and
      transmission to germline cells of the LV were excluded by different molecular
      assays. Analysis of vector integrations showed polyclonal integration patterns in
      vitro and in human engrafted cells in vivo. In summary, this work establishes the
      preclinical safety and efficacy of human CD34(+) cells gene therapy for the
      treatment of WAS.

PMID- 22371847
TI  - Association of alcohol consumption with lipid profile in hypertensive men.
AB  - AIMS: Alcohol consumption is known to be closely related with alterations in
      blood lipid levels as well as in blood pressure. The objective of this study was
      to evaluate the association between alcohol consumption and blood lipid levels in
      hypertensive men. METHODS: A cross-sectional study involving participants (n =
      2014) aged 20-69 years from the Korea National Health and Nutrition Examination
      Survey, 1998-2009. Demographic characteristics, dietary intake and medical
      history were obtained from the participants by questionnaire, and lipid levels
      were determined by analysis of blood samples. RESULTS: After adjusting for
      demographic and dietary factors, alcohol consumption was negatively associated
      with risk of low high-density lipoprotein cholesterol [HDL-C; odds ratio (OR):
      0.29, 95% confidence interval (CI): 0.22-0.40 in heavy (>=30 g/day) drinkers; P
      for trend <0.001], whereas the risk of high triglycerides increased with
      increasing alcohol consumption (OR: 2.04, 95% CI: 1.53-2.72 in heavy drinkers; P
      for trend <0.001). However, the OR of high non-HDL-C and the ratio of high
      triglycerides to HDL-C did not change significantly with an increase in alcohol
      consumption. CONCLUSION: These data suggest that alcohol consumption
      differentially affected lipid measures according to the amount of alcohol intake
      in hypertensive men.

PMID- 22371848
TI  - Hypnotics' association with mortality or cancer: a matched cohort study.
AB  - OBJECTIVES: An estimated 6%-10% of US adults took a hypnotic drug for poor sleep
      in 2010. This study extends previous reports associating hypnotics with excess
      mortality. SETTING: A large integrated health system in the USA. DESIGN:
      Longitudinal electronic medical records were extracted for a one-to-two matched
      cohort survival analysis. SUBJECTS: Subjects (mean age 54 years) were 10 529
      patients who received hypnotic prescriptions and 23 676 matched controls with no
      hypnotic prescriptions, followed for an average of 2.5 years between January 2002
      and January 2007. MAIN OUTCOME MEASURES: Data were adjusted for age, gender,
      smoking, body mass index, ethnicity, marital status, alcohol use and prior
      cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards
      models controlled for risk factors and using up to 116 strata, which exactly
      matched cases and controls by 12 classes of comorbidity. RESULTS: As predicted,
      patients prescribed any hypnotic had substantially elevated hazards of dying
      compared to those prescribed no hypnotics. For groups prescribed 0.4-18, 18-132
      and >132 doses/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36)
      and 5.32 (4.50 to 6.30), respectively, demonstrating a dose-response association.
      HRs were elevated in separate analyses for several common hypnotics, including
      zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates
      and sedative antihistamines. Hypnotic use in the upper third was associated with
      a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55).
      Results were robust within groups suffering each comorbidity, indicating that the
      death and cancer hazards associated with hypnotic drugs were not attributable to
      pre-existing disease. CONCLUSIONS: Receiving hypnotic prescriptions was
      associated with greater than threefold increased hazards of death even when
      prescribed <18 pills/year. This association held in separate analyses for several
      commonly used hypnotics and for newer shorter-acting drugs. Control of selective
      prescription of hypnotics for patients in poor health did not explain the
      observed excess mortality.

PMID- 22371849
TI  - Antivirals for treatment of influenza: a systematic review and meta-analysis of
      observational studies.
AB  - BACKGROUND: Systematic reviews of randomized, controlled trials in patients with
      influenza suggest a lack of evidence about the effects of antiviral therapy on
      several patient-important outcomes of influenza. PURPOSE: To systematically
      review observational studies for benefits and harms of oseltamivir, zanamivir,
      amantadine, or rimantadine in the treatment of influenza. DATA SOURCES: MEDLINE,
      EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the
      Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November
      2010; contact with pharmaceutical companies; and reference lists. STUDY
      SELECTION: Observational studies in any language that compared single antiviral
      therapy with no therapy or other antiviral therapy, or that had no comparator,
      for influenza or influenza-like illness. DATA EXTRACTION: Two independent
      investigators extracted data. Confidence in the estimates of the obtained effects
      (quality of evidence) was assessed by using the Grading of Recommendations
      Assessment, Development, and Evaluation approach. DATA SYNTHESIS: 74 studies
      fulfilled the inclusion criteria. Meta-analyses of the few studies providing
      effects with adjustment for confounders suggest that, in high-risk populations,
      oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43];
      low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low
      quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very
      low-quality evidence) compared with no treatment. Earlier treatment with
      oseltamivir was generally associated with better outcomes. Inhaled zanamivir may
      lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality
      evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but
      more complications than no treatment. Direct comparison of oral oseltamivir and
      inhaled zanamivir suggests no important differences in key outcomes. Data from 1
      study suggest that oral amantadine may reduce mortality and pneumonia associated
      with influenza A. No included study evaluated rimantadine. LIMITATIONS: Mortality
      was assessed in high-risk patients, and generalizability is limited. The overall
      body of evidence is limited by risk for confounding and selection, reporting, and
      publication bias. CONCLUSION: Therapy with oral oseltamivir and inhaled zanamivir
      may provide a net benefit over no treatment of influenza. However, as with the
      randomized trials, the confidence in the estimates of the effects for decision
      making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and
      McMaster University.

PMID- 22371850
TI  - Accuracy of rapid influenza diagnostic tests: a meta-analysis.
AB  - BACKGROUND: Timely diagnosis of influenza can help clinical management. PURPOSE:
      To examine the accuracy of rapid influenza diagnostic tests (RIDTs) in adults and
      children with influenza-like illness and evaluate factors associated with higher
      accuracy. DATA SOURCES: PubMed and EMBASE through December 2011; BIOSIS and Web
      of Science through March 2010; and citations of articles, guidelines, reviews,
      and manufacturers. STUDY SELECTION: Studies that compared RIDTs with a reference
      standard of either reverse transcriptase polymerase chain reaction (first choice)
      or viral culture. DATA EXTRACTION: Reviewers abstracted study data by using a
      standardized form and assessed quality by using Quality Assessment of Diagnostic
      Accuracy Studies criteria. DATA SYNTHESIS: 159 studies evaluated 26 RIDTs, and
      35% were conducted during the H1N1 pandemic. Failure to report whether results
      were assessed in a blinded manner and the basis for patient recruitment were
      important quality concerns. The pooled sensitivity and specificity were 62.3%
      (95% CI, 57.9% to 66.6%) and 98.2% (CI, 97.5% to 98.7%), respectively. The
      positive and negative likelihood ratios were 34.5 (CI, 23.8 to 45.2) and 0.38
      (CI, 0.34 to 0.43), respectively. Sensitivity estimates were highly
      heterogeneous, which was partially explained by lower sensitivity in adults
      (53.9% [CI, 47.9% to 59.8%]) than in children (66.6% [CI, 61.6% to 71.7%]) and a
      higher sensitivity for influenza A (64.6% [CI, 59.0% to 70.1%) than for influenza
      B (52.2% [CI, 45.0% to 59.3%). LIMITATION: Incomplete reporting limited the
      ability to assess the effect of important factors, such as specimen type and
      duration of influenza symptoms, on diagnostic accuracy. CONCLUSION: Influenza can
      be ruled in but not ruled out through the use of RIDTs. Sensitivity varies across
      populations, but it is higher in children than in adults and for influenza A than
      for influenza B. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

PMID- 22371851
TI  - Brain air embolism secondary to atrial-esophageal fistula.

PMID- 22371852
TI  - Evidence of intrathecal immunoglobulin synthesis in stroke: a cohort study.
AB  - BACKGROUND: Immune mechanisms are included in stroke pathophysiologic factors,
      but the frequency and role of intrathecal antibodies is unclear and diagnostic
      tests are not routinely performed on cerebrospinal fluid (CSF). OBJECTIVE: To
      determine the frequency of intrathecal immunoglobulin synthesis in a well
      characterized cohort of patients who experienced "noninflammatory"acute stroke.
      DESIGN: Retrospective cohort study. SETTING: University hospital neurology
      department. PATIENTS: Patients (n=318) with stroke who were undergoing lumbar
      puncture during diagnostic workup and 79 control patients. RESULTS: Cerebrospinal
      fluid-specific immunoglobulin(IgG, IgM, and IgA) synthesis was
      significantly(P.001) more frequent after stroke (24.8%) compared with the
      incidence in age- and sex-matched controls(2.5%). Furthermore, 31.3% of stroke
      patients demonstrated blood-brain barrier dysfunction and 18.1% displayed
      pleocytosis. CONCLUSION: The strong association between CSF-specific
      immunoglobulin synthesis and stroke suggests a role in the development of
      cerebral ischemia and might constitute an immunologically defined stroke
      subgroup.

PMID- 22371853
TI  - Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with
      optic neuritis.
AB  - OBJECTIVE: To study the humoral immune response directed at myelin
      oligodendrocyte glycoprotein (MOG)in pediatric patients with isolated and
      recurrent optic neuritis(ON). DESIGN: Observational prospective case series.
      SETTING: Six pediatric hospitals in Germany and Austria. PATIENTS: Thirty-seven
      patients 18 years or younger with single or recurrent episodes of ON were
      recruited from 6 different hospitals. MAIN OUTCOME MEASURES: Clinical features,
      magnetic resonance imaging findings, intrathecal IgG synthesis,and outcome were
      recorded. A live cell-based immunofluorescence assay was used to measure serum
      IgG antibodies to MOG and aquaporin 4. RESULTS: A single episode of ON was
      observed in 10 patients,and 15 experienced 2 to 12 episodes. The acute episode of
      ON was part of a clinically isolated syndrome in 12 patients, of whom 8 were
      subsequently classified as having multiple sclerosis. High-titer serum MOG-IgG
      antibodies (1:160) were detected in 17 patients (46%).In addition, high titers of
      MOG-IgG antibodies were more frequently observed in 12 of the 15 patients with
      recurrent episodes of ON (80%; median titer, 1:640)compared with 2 of the 10
      patients with monophasic ON(20%; median titer, 0) and 3 of the 12 patients with
      ON as part of a clinically isolated syndrome (25%; median titer, 0). CONCLUSION:
      High-titer MOG-IgG antibodies are predominantly detected in pediatric patients
      with recurrent ON, indicating that anti-MOG-specific antibodies may exert a
      direct role in the pathogenesis of ON in this subgroup.

PMID- 22371854
TI  - Adult-onset cerebral folate deficiency.
AB  - OBJECTIVE: To report new manifestations of cerebral folate deficiency, a rare
      metabolic autoimmune syndrome,in an adult. DESIGN: Case report. SETTING:
      University teaching hospital. PATIENT: A 58-year-old woman with progressive
      memory loss and myoclonus presented for medical attention. Results of cerebral
      spinal fluid analysis showed low levels of tetrahydrobiopterin and 5
      methyltetrahydrofolate. The patient's serum folate level was normal. Serum
      contained folate receptor 1 blocking and binding antibodies. RESULTS: The patient
      was treated successfully with folinic acid supplementation, and after 6 months of
      treatment,clinical symptoms had resolved. CONCLUSIONS: To our knowledge, we
      report the first case of adult-onset cerebral folate deficiency. Furthermore,
      this condition could represent a treatable form of early-onset dementia.

PMID- 22371855
TI  - Frequency of local, regional, and long-distance dispersal of diploid and
      tetraploid Saxifraga oppositifolia (Saxifragaceae) to Arctic glacier forelands.
AB  - PREMISE OF THE STUDY: Climate change forces many species to migrate. Empirical
      small-scale data on migration and colonization in the Arctic are scarce.
      Retreating glaciers provide new territory for cold-adapted plant species, but the
      genetic consequences depend on dispersal distances and frequencies. We estimated
      local, regional, and long-distance dispersal frequencies, as well as their effect
      on levels of genetic diversity, in diploid and tetraploid individuals of
      Saxifraga oppositifolia. METHODS: Samples were collected in four aged moraines in
      each of three glacier forelands, in surrounding areas and reference populations
      in the Arctic archipelago Svalbard. These samples were analyzed for neutral
      amplified fragment length polymorphisms (AFLPs, n = 707) and ploidy levels (n =
      30). KEY RESULTS: Genetic clustering and ploidy analyses revealed two distinct
      genetic groups representing diploids and tetraploids, with few intermediate
      triploids. The groups were intermixed in most sampled populations. No differences
      in genetic diversity were found between tetraploids and diploids, or between
      established and glacier foreland populations. Seeds were dispersed over local,
      regional, and long distances, with the highest proportions of seeds originating
      from close sources. A minimum of 4-15 founding individuals from several source
      populations had initially established in each glacier foreland. CONCLUSIONS: Our
      data suggest that S. oppositifolia can rapidly colonize new deglaciated areas
      without losing genetic diversity. Thus, glacier forelands can be alternative
      habitats for cold-adapted vascular plants tracking their climatic niche. Our data
      show no difference in colonization success between diploid and tetraploid
      individuals.

PMID- 22371856
TI  - Development and characterization of 20 new polymorphic microsatellite markers
      from Mangifera indica (Anacardiaceae).
AB  - PREMISE OF THE STUDY: Twenty microsatellite loci for mango (Mangifera indica), an
      important commercial fruit tree in East Asia, were developed to evaluate the
      genetic diversity and identification of cultivars. METHODS AND RESULTS: The 20
      new microsatellite markers were isolated from mango using a magnetic bead
      enrichment method, and polymorphisms were identified in 22 mango cultivars. The
      number of alleles ranged from one to nine, with expected heterozygosity ranging
      from 0 to 0.826. The polymorphism information content ranged from 0 to 0.756 with
      a mean of 0.525. CONCLUSIONS: These new microsatellite loci should be useful and
      convenient for further studies of the genetic diversity and identification of
      cultivars in mango.

PMID- 22371857
TI  - Computer simulations support a core prediction of a contentious plant model.
AB  - PREMISE OF THE STUDY: An overarching but vigorously debated plant model proposed
      by the West, Brown, Enquist (WBE) theory predicts the scaling relationships for
      numerous botanical phenomena. However, few studies have evaluated this model's
      basic assumptions, one of which is that natural selection has resulted in
      hierarchal networks that minimize the energy required to distribute nutrients
      internally and have thus produced highly efficient organisms. METHODS: If these
      core assumptions are correct, an "idealized" plant complying with all of the
      scaling relationships emerging from the WBE plant model should rapidly outcompete
      other plants, even those that differ slightly from it. To test this reasoning, a
      computer model was used to simulate competition between an idealized WBE plant, a
      generic "average" angiosperm (GA), and one of seven variants of the idealized WBE
      plant, each being similar to the GA in one of the GA's scaling parameters. KEY
      RESULTS: Replicate simulations show that the idealized WBE plant rapidly
      outcompetes all other plants under light-shade and open-field conditions.
      However, changing only one of the WBE's scaling parameters results in death or in
      the coexistence of WBE and GA plants. CONCLUSIONS: These simulations support a
      core assumption of the WBE plant model and suggest why this idealized plant has
      not evolved.

PMID- 22371858
TI  - Isolation and characterization of 36 polymorphic microsatellite markers in Schima
      superba (Theaceae).
AB  - PREMISE OF THE STUDY: Our objective was to develop microsatellite markers to
      investigate the level of genetic diversity within and among populations in a
      dominant evergreen broad-leaved tree, Schima superba, in southern China. METHODS
      AND RESULTS: Thirty-six microsatellite markers were developed and showed
      polymorphism in three populations. The number of alleles per locus ranged from
      six to 34, with an average of 19. The observed and expected heterozygosities
      ranged from 0.242 to 1.000 and from 0.504 to 0.945, respectively. CONCLUSIONS:
      The developed microsatellites will be useful for studying genetic diversity and
      population structure in S. superba.

PMID- 22371859
TI  - Observer bias in randomised clinical trials with binary outcomes: systematic
      review of trials with both blinded and non-blinded outcome assessors.
AB  - OBJECTIVE: To evaluate the impact of non-blinded outcome assessment on estimated
      treatment effects in randomised clinical trials with binary outcomes. DESIGN:
      Systematic review of trials with both blinded and non-blinded assessment of the
      same binary outcome. For each trial we calculated the ratio of the odds ratios-
      the odds ratio from non-blinded assessments relative to the corresponding odds
      ratio from blinded assessments. A ratio of odds ratios <1 indicated that non
      blinded assessors generated more optimistic effect estimates than blinded
      assessors. We pooled the individual ratios of odds ratios with inverse variance
      random effects meta-analysis and explored reasons for variation in ratios of odds
      ratios with meta-regression. We also analysed rates of agreement between blinded
      and non-blinded assessors and calculated the number of patients needed to be
      reclassified to neutralise any bias. DATA SOURCES: PubMed, Embase, PsycINFO,
      CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press, and
      Google Scholar. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical
      trials with blinded and non-blinded assessment of the same binary outcome.
      RESULTS: We included 21 trials in the main analysis (with 4391 patients); eight
      trials provided individual patient data. Outcomes in most trials were subjective-
      for example, qualitative assessment of the patient's function. The ratio of the
      odds ratios ranged from 0.02 to 14.4. The pooled ratio of odds ratios was 0.64
      (95% confidence interval 0.43 to 0.96), indicating an average exaggeration of the
      non-blinded odds ratio by 36%. We found no significant association between low
      ratios of odds ratios and scores for outcome subjectivity (P=0.27); non-blinded
      assessor's overall involvement in the trial (P=0.60); or outcome vulnerability to
      non-blinded patients (P=0.52). Blinded and non-blinded assessors agreed in a
      median of 78% of assessments (interquartile range 64-90%) in the 12 trials with
      available data. The exaggeration of treatment effects associated with non-blinded
      assessors was induced by the misclassification of a median of 3% of the assessed
      patients per trial (1-7%). CONCLUSIONS: On average, non-blinded assessors of
      subjective binary outcomes generated substantially biased effect estimates in
      randomised clinical trials, exaggerating odds ratios by 36%. This bias was
      compatible with a high rate of agreement between blinded and non-blinded outcome
      assessors and driven by the misclassification of few patients.

PMID- 22371860
TI  - "Academic spring" sees widening boycott of Elsevier.

PMID- 22371861
TI  - Doctors are to be balloted on what action to take over pensions.

PMID- 22371862
TI  - Police and GMC investigate claims that doctors have aborted fetuses on basis of
      sex.

PMID- 22371863
TI  - NHS will soon have to specify what care is and what isn't freely available, GPs
      say.

PMID- 22371864
TI  - Scientific evidence alone is not sufficient basis for health policy.

PMID- 22371865
TI  - Doctors may decide that effects of a fetus's sex justify an abortion, says new
      BMA ethics guide.

PMID- 22371866
TI  - NHS patients are choosing to have PIP implants removed whether or not they have
      burst.

PMID- 22371867
TI  - Meta-analysis of individual patient data in randomised trials of self monitoring
      of blood glucose in people with non-insulin treated type 2 diabetes.
AB  - OBJECTIVE: To assess the effectiveness of self monitoring blood glucose levels in
      people with non-insulin treated type 2 diabetes compared with clinical management
      without self monitoring, and to explore the effects in specific patient groups.
      DESIGN: Meta-analysis based on individual participant data. DATA SOURCES:
      Medline, Embase, and a recent systematic review of trials on self monitoring of
      blood glucose. Chief investigators of trials published since 2000 were approached
      for additional information and individual patient data. INCLUSION CRITERIA:
      Randomised controlled trials in patients with non-insulin treated type 2 diabetes
      comparing an intervention using self monitoring of blood glucose with clinical
      management not using self monitoring. Trials published from 2000 with at least 80
      participants were included. DATA COLLECTION: Individual patient data were
      collected from electronic files and checked for integrity. ANALYSIS: All
      randomised participants were analysed using the intention to treat principle. A
      random effects model of complete cases was used to assess efficacy, a sensitivity
      analysis comprised imputed data, and prespecified subgroup analyses were carried
      out for age, sex, previous use of self monitoring, duration of diabetes, and
      levels of glycated haemoglobin (HbA(1c)) at baseline. RESULTS: 2552 patients were
      randomised in the six included trials. A mean reduction in HbA(1c) level of -2.7
      mmol/mol (95% confidence interval -3.9 to -1.6; 0.25%) was observed for those
      using self monitoring of blood glucose levels compared with no self monitoring at
      six months. The mean reduction in HbA(1c) level between groups was 2.0 mmol/mol
      (3.2 to 0.8; 0.25%) at three months (five trials) and 2.5 mmol/mol (4.1 to 0.9;
      0.35%) at 12 months (three trials). These estimates were unchanged after imputing
      missing data, and estimates of effect in trials with higher loss to follow-up or
      a possibility of co-intervention compared with those with lower loss to follow-up
      and no co-intervention did not differ significantly (P=0.21). The difference in
      HbA(1c) levels between groups was consistent across age, baseline HbA(1c) level,
      sex, and duration of diabetes, although the numbers of older and younger people
      and those with HbA(1c) levels >86 mmol/mol (10%) were insufficient for
      interpretation. No changes occurred in systolic blood pressure (-0.2 mm Hg, 95%
      confidence interval -1.4 to 1.0), diastolic blood pressure (-0.1 mm Hg, -0.9 to
      0.6), or total cholesterol level (-0.1 mol/L, 95% confidence interval -0.2 to
      0.1). CONCLUSIONS: Evidence from this meta-analysis of individual patient data
      was not convincing for a clinically meaningful effect of clinical management of
      non-insulin treated type 2 diabetes by self monitoring of blood glucose levels
      compared with management without self monitoring, although the difference in
      HbA(1c) level between groups was statistically significant. The difference in
      levels was consistent across subgroups defined by personal and clinical
      characteristics.

PMID- 22371868
TI  - Facial view I.

PMID- 22371869
TI  - Bones of the hand I.

PMID- 22371870
TI  - Bones of the hand II.

PMID- 22371871
TI  - Interpreting biomarkers during percutaneous coronary intervention: the need to
      reevaluate our approach.

PMID- 22371872
TI  - Trial of prevention and reduction of obesity through active living in clinical
      settings: a randomized controlled trial.
AB  - BACKGROUND: The efficacy of physical activity with a healthful diet to reduce
      obesity is established; however, little is known about the translation of
      effective lifestyle strategies for obesity reduction in primary care settings.
      METHODS: We assessed the effectiveness of a 2-year behaviorally based physical
      activity and diet program implemented entirely within clinical practices to
      reduce obesity. A total of 490 sedentary, obese adults were randomized to usual
      care (n = 241) or to the behavioral intervention (n = 249). The usual care group
      received advice from their physicians about lifestyle as a strategy for obesity
      reduction. The behavioral intervention included individual counseling from health
      educators to promote physical activity with a healthful diet. The primary outcome
      was change in waist circumference (WC). RESULTS: A total of 396 participants
      completed the trial (80.8%). A significant main effect was observed for WC change
      within the intervention compared with usual care (P < .001) that was sustained at
      24 months (mean [SE], -0.9 [0.4] vs 0.2 [0.4] cm; P = .05). Secondary analyses
      revealed significant main effects for change in WC in men (P = .009) and women (P
      = .02). In men, the mean (SE) reduction in WC at 24 months was greater with
      behavioral intervention compared with usual care (-1.6 [0.6] vs 0.1 [0.6] cm; P =
      .049). In women, the behavioral intervention was associated with differences in
      WC compared with usual care at 6 and 12 months (P <= .01) but not at 24 months (P
      = .10). CONCLUSIONS: Behavioral intervention in clinical settings is associated
      with modest reductions in WC during a 2-year study in obese patients. However,
      the effectiveness of the intervention is restricted to men. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00665158.

PMID- 22371873
TI  - Estimating influenza vaccine effectiveness in community-dwelling elderly patients
      using the instrumental variable analysis method.
AB  - BACKGROUND: Estimates of influenza vaccine effectiveness in elderly individuals
      are largely from observational studies, which are susceptible to bias.
      Instrumental variable (IV) methods control for overt and hidden biases in
      observational studies. METHODS: We used linked health administrative databases in
      Ontario to examine the association between influenza vaccination and all-cause
      mortality among community-dwelling individuals older than 65 years for 9
      influenza seasons (2000-2001 to 2008-2009). We examined the composite of
      hospitalization for pneumonia and influenza and all-cause mortality as a
      secondary outcome. We used logistic regression modeling and IV analysis to remove
      the effect of selection bias. RESULTS: We included 12 621 806 person-influenza
      seasons of observation. Logistic regression produced adjusted odds ratios of 0.67
      (95% CI, 0.62-0.72) for all-cause mortality during influenza seasons and 0.85
      (0.83-0.86) during post-influenza seasons when influenza is not circulating,
      suggesting the presence of bias. In contrast, IV analysis yielded adjusted odds
      ratios of 0.94 (95% CI, 0.84-1.03) during influenza seasons and 1.13 (1.07-1.19)
      during post-influenza seasons. For the composite of hospitalization for pneumonia
      and influenza and death, logistic regression produced adjusted odds ratios of
      0.74 (95% CI, 0.70-0.78) during influenza seasons and 0.88 (0.87-0.90) during
      post-influenza seasons, whereas IV analysis produced adjusted odds ratios of 0.86
      (95% CI, 0.79-0.92) and 1.02 (0.97-1.06), respectively. CONCLUSIONS: Influenza
      vaccination is associated with reductions in the composite of hospitalizations
      for pneumonia and influenza and all-cause mortality during the influenza season
      but not mortality alone. Compared with standard modeling, IV analysis appears to
      produce less-biased estimates of vaccine effectiveness.

PMID- 22371874
TI  - Troponin criteria for myocardial infarction after percutaneous coronary
      intervention.
AB  - BACKGROUND: The universal definition of myocardial infarction specifies creatine
      kinase-MB fraction (CKMB) or troponin values more than 3 times the 99th
      percentile of the upper reference limit as diagnostic after percutaneous coronary
      intervention, with a preference for the use of troponin. METHODS: Outcomes of
      4930 patients with elective coronary stent placement between July 1, 2004, and
      September 30, 2007, as part of the EVENT (Evaluation of Drug Eluting Stents and
      Ischemic Events) registry were analyzed to test the association between 1-year
      mortality and postprocedure elevation of either CKMB or troponin. All values were
      normalized to the individual clinical center myocardial infarction diagnostic
      levels. RESULTS: Myocardial infarction occurred in 7.2% of patients by the CKMB
      criteria and in 24.3% of patients by the troponin criteria of greater than 3
      times the diagnostic level. Both CKMB (hazard ratio [HR], 1.38; 95% CI, 1.22
      1.55) and troponin (HR, 1.35; 95% CI, 1.18-1.54) as continuous values were
      associated with 1-year mortality. The mortality effect of a more than 3-fold
      increase was greater for CKMB (adjusted HR, 2.5; 95% CI, 1.5-4.1) than for
      troponin (adjusted HR, 1.7; 95% CI, 1.1-2.5). A troponin threshold more than 20
      times the diagnostic level provided similar frequency (7.0%) and mortality risk
      (adjusted HR, 2.6; 95% CI, 1.6-4.3) as a 3-fold increase in CKMB. A regression
      spline model of the relationship between troponin and 1-year mortality
      demonstrated that the hazard of mortality increased from 1.02 at 3-fold to 1.67
      at 20-fold troponin elevation. CONCLUSION: Troponin and CKMB elevations after
      percutaneous coronary intervention are associated with increased 1-year mortality
      rates, but thresholds for similar event frequency and mortality hazard are much
      higher for troponin than for CKMB.

PMID- 22371875
TI  - The influenza vaccine in elderly persons: a shot in the dark?

PMID- 22371876
TI  - Osteoporosis telephonic intervention to improve medication regimen adherence: a
      large, pragmatic, randomized controlled trial.
AB  - BACKGROUND: Multiple studies demonstrate poor adherence to medication regimens
      prescribed for chronic illnesses, including osteoporosis, but few interventions
      have been proven to enhance adherence. We examined the effectiveness of a
      telephone-based counseling program rooted in motivational interviewing to improve
      adherence to a medication regimen for osteoporosis. METHODS: We conducted a 1
      year randomized controlled clinical trial. Participants were recruited from a
      large pharmacy benefits program for Medicare beneficiaries. All potentially
      eligible individuals had been newly prescribed a medication for osteoporosis.
      Consenting participants were randomized to a program of telephone-based
      counseling (n = 1046) using a motivational interviewing framework or a control
      group (n = 1041) that received mailed educational materials. Medication regimen
      adherence was the primary outcome compared across treatment arms and was measured
      as the median (interquartile range) medication possession ratio, calculated as
      the ratio of days with filled prescriptions to total days of follow-up. RESULTS:
      The groups were balanced at baseline, with a mean age of 78 years; 93.8% were
      female. In an intention-to-treat analysis, median adherence was 49%
      (interquartile range, 7%-88%) in the intervention arm and 41% (2%-86%) in the
      control arm (P = .07, Kruskal-Wallis test). There were no differences in self
      reported fractures. CONCLUSION: In this randomized controlled trial, we did not
      find a statistically significant improvement in adherence to an osteoporosis
      medication regimen using a telephonic motivational interviewing intervention.

PMID- 22371877
TI  - Does motivational interviewing improve outcomes?

PMID- 22371878
TI  - Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and
      dasatinib and/or nilotinib therapy failure.
AB  - Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent
      activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated
      the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after
      resistance/intolerance to imatinib. The current analysis included 118 patients
      with chronic-phase CML who had been pretreated with imatinib followed by
      dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this
      subpopulation, major cytogenetic response was attained by 32% of patients;
      complete cytogenetic response was attained by 24%, including in one of 3 patients
      treated with 3 prior TKIs. Complete hematologic response was achieved/maintained
      in 73% of patients. On-treatment transformation to accelerated/blast phase
      occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free
      survival was 73% and estimated overall survival was 83%. Responses were seen
      across Bcr-Abl mutations, including those associated with dasatinib and nilotinib
      resistance, except T315I. Bosutinib had an acceptable safety profile; treatment
      emergent adverse events were primarily manageable grade 1/2 gastrointestinal
      events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients)
      included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option
      for patients with chronic-phase CML after treatment with multiple TKIs. This
      trial was registered at www.clinicaltrials.gov as NCT00261846.

PMID- 22371879
TI  - Blood T-cell receptor diversity decreases during the course of HIV infection, but
      the potential for a diverse repertoire persists.
AB  - HIV infection results in a decrease in circulating CD4(+) T-cell and naive T-cell
      numbers. If such losses were associated with an erosion of T-cell receptor (TCR)
      repertoire diversity in the peripheral T-cell pool, this might exacerbate the
      state of persistent immunodeficiency. Existing methods for the analysis of the
      TCR repertoire have demonstrated skewed distributions of TCR genes in HIV
      infected subjects but cannot directly measure TCR diversity. Here we used
      AmpliCot, a quantitative assay based on DNA hybridization kinetics, to measure
      TCR diversity in a cross-sectional comparison of 19 HIV-infected persons to 18
      HIV-uninfected controls. HIV-infected persons had a 10-fold decrease in total TCR
      repertoire diversity in 1.5 mL of blood compared with uninfected controls, with
      decreased diversity correlating most closely with a lower CD4(+) T-cell
      percentage. Nonetheless, the TCR repertoire diversity of sort-purified T-cell
      subpopulations in HIV-infected and HIV-uninfected subjects was comparable. These
      observations suggest that the TCR repertoire diversity changes in whole blood
      during HIV disease progression are primarily the result of changes in the number
      and proportion of T-cell subpopulations and that most HIV-infected persons may
      retain a sufficiently diverse TCR repertoire to permit immune reconstitution with
      antiretroviral therapy alone, without thymopoiesis.

PMID- 22371880
TI  - CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic
      potential.
AB  - A unique subset of CD86(-) HSCs was previously discovered in mice that were old
      or chronically stimulated with lipopolysaccharide. Functionally defective HSCs
      were also present in those animals, and we now show that CD86(-) CD150(+) CD48(-)
      HSCs from normal adult mice are particularly poor at restoring the adaptive
      immune system. Levels of the marker are high on all progenitors with
      lymphopoietic potential, and progressive loss helps to establish relations
      between progenitors corresponding to myeloid and erythroid lineages. CD86
      represents an important tool for subdividing HSCs in several circumstances,
      identifying those unlikely to generate a full spectrum of hematopoietic cells.

PMID- 22371881
TI  - A novel mechanism of sustained platelet alphaIIbbeta3 activation via PEAR1.
AB  - Because single nucleotide polymorphisms (SNPs) in platelet endothelial
      aggregation receptor 1 (PEAR1) are associated with differential functional
      platelet responses in healthy subjects, we studied the function of PEAR1 in human
      platelets. During platelet aggregation by various agonists, the membrane
      expression of PEAR1 and its tyrosine phosphorylation increased. The recombinant
      PEAR1 EMI domain (GST-EMI) competitively reduced platelet adhesion to surface
      coated PEAR1, diminished platelet aggregation, and eliminated PEAR1
      phosphorylation. Polyclonal antibodies against the extracellular PEAR1 domain
      triggered PEAR1 phosphorylation in a src family kinase (SFK)-dependent manner.
      Such resulted in downstream signaling, culminating in extensive platelet
      degranulation and irreversible aggregation reactions interrupted by excess
      monovalent anti-GST-EMI F(ab) fragments. In resting platelets, the cytoplasmic
      tail of PEAR1 was found complexed to c-Src and Fyn, but on its phosphorylation,
      phospho-PEAR1 recruited p85 PI3K, resulting in persistent activation of PI3K and
      Akt. Thus, alphaIIbbeta3 activation was amplified, hence stabilizing platelet
      aggregates, a signaling cascade fully interrupted by the SFK inhibitor PP1 and
      the PI3K inhibitor LY294002. This study is the first demonstration of a
      functional role for PEAR1 in platelet activation, underpinning the observed
      association between PEAR1 and platelet function in genome-wide association
      studies.

PMID- 22371882
TI  - Overcoming reprogramming resistance of Fanconi anemia cells.
AB  - Fanconi anemia (FA) is a recessive syndrome characterized by progressive fatal BM
      failure and chromosomal instability. FA cells have inactivating mutations in a
      signaling pathway that is critical for maintaining genomic integrity and
      protecting cells from the DNA damage caused by cross-linking agents. Transgenic
      expression of the implicated genes corrects the phenotype of hematopoietic cells,
      but previous attempts at gene therapy have failed largely because of inadequate
      numbers of hematopoietic stem cells available for gene correction. Induced
      pluripotent stem cells (iPSCs) constitute an alternate source of autologous cells
      that are amenable to ex vivo expansion, genetic correction, and molecular
      characterization. In the present study, we demonstrate that reprogramming leads
      to activation of the FA pathway, increased DNA double-strand breaks, and
      senescence. We also demonstrate that defects in the FA DNA-repair pathway
      decrease the reprogramming efficiency of murine and human primary cells. FA
      pathway complementation reduces senescence and restores the reprogramming
      efficiency of somatic FA cells to normal levels. Disease-specific iPSCs derived
      in this fashion maintain a normal karyotype and are capable of hematopoietic
      differentiation. These data define the role of the FA pathway in reprogramming
      and provide a strategy for future translational applications of patient-specific
      FA iPSCs.

PMID- 22371883
TI  - TCR-transgenic lymphocytes specific for HMMR/Rhamm limit tumor outgrowth in vivo.
AB  - The hyaluronan-mediated motility receptor (HMMR/Rhamm) is overexpressed in
      numerous tumor types, including acute lymphoid leukemia and acute myeloid
      leukemia (AML). Several studies have reported the existence of T-cell responses
      directed against HMMR in AML patients that are linked to better clinical outcome.
      Therefore, we explored the use of HMMR-specific TCRs for transgenic expression in
      lymphocytes and their in vivo impact on HMMR(+) solid tumors and disseminated
      leukemia. We obtained TCRs via an in vitro priming approach in combination with
      CD137-mediated enrichment. Recipient lymphocytes expressing transgenic TCR
      revealed the specific tumor recognition pattern seen with the original T cells.
      Adoptive transfer experiments using a humanized xenograft mouse model resulted in
      significantly retarded solid tumor outgrowth, which was enhanced using IL-15
      conditioned, TCR-transgenic effector memory cells. These cells also showed an
      increased potency to retard the outgrowth of disseminated AML, and this was
      further improved using CD8-enriched effector memory cells. To define a safe
      clinical setting for HMMR-TCR gene therapy, we analyzed transgenic T-cell
      recognition of hematopoietic stem cells (HSCs) and found on-target killing of HLA
      A2(+) HSCs. Our findings clearly limit the use of HMMR-TCR therapy to MHC-
      mismatched HSC transplantation, in which HLA-A2 differences can be used to
      restrict recognition to patient HSCs and leukemia.

PMID- 22371884
TI  - Sequential gain of mutations in severe congenital neutropenia progressing to
      acute myeloid leukemia.
AB  - Severe congenital neutropenia (SCN) is a BM failure syndrome with a high risk of
      progression to acute myeloid leukemia (AML). The underlying genetic changes
      involved in SCN evolution to AML are largely unknown. We obtained serial
      hematopoietic samples from an SCN patient who developed AML 17 years after the
      initiation of G-CSF treatment. Next- generation sequencing was performed to
      identify mutations during disease progression. In the AML phase, we found 12
      acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co
      occurred in a subpopulation of progenitor cells already in the early SCN phase.
      This population expanded over time, whereas clones harboring only CSF3R mutations
      disappeared from the BM. The other 9 mutations were only apparent in the AML
      cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin
      remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred
      autonomous proliferation to myeloid progenitors was found. We conclude that
      progression from SCN to AML is a multistep process, with distinct mutations
      arising early during the SCN phase and others later in AML development. The
      sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a
      driver of leukemic transformation in this case of SCN.

PMID- 22371885
TI  - Graft invariant natural killer T-cell dose predicts risk of acute graft-versus
      host disease in allogeneic hematopoietic stem cell transplantation.
AB  - Invariant natural killer T (iNKT) cells are powerful immunomodulatory cells that
      in mice regulate a variety of immune responses, including acute GVHD (aGVHD).
      However, their clinical relevance and in particular their role in clinical aGVHD
      are not known. We studied whether peripheral blood stem cell (PBSC) graft iNKT
      cell dose affects on the occurrence of clinically significant grade II-IV aGVHD
      in patients (n = 57) undergoing sibling, HLA-identical allogeneic HSCT. In
      multivariate analysis, CD4(-) iNKT-cell dose was the only graft parameter to
      predict clinically significant aGVHD. The cumulative incidence of grade II-IV
      aGVHD in patients receiving CD4(-) iNKT-cell doses above and below the median
      were 24.2% and 71.4%, respectively (P = .0008); low CD4(-) iNKT-cell dose was
      associated with a relative risk of grade II-IV aGVHD of 4.27 (P = .0023; 95% CI,
      1.68-10.85). Consistent with a role of iNKT cells in regulating aGVHD, in mixed
      lymphocyte reaction assays, CD4(-) iNKT cells effectively suppressed T-cell
      proliferation and IFN-gamma secretion in a contact-dependent manner. In
      conclusion, higher doses of CD4(-) iNKT cells in PBSC grafts are associated with
      protection from aGVHD. This effect could be harnessed for prevention of aGVHD.

PMID- 22371886
TI  - Development and function of murine RORgammat+ iNKT cells are under TGF-beta
      signaling control.
AB  - Invariant natural killer T (iNKT) cells have the ability to rapidly secret
      cytokines in response to diverse stimuli, and therefore influence numerous immune
      reactions. Although IFN-gamma and IL-4 are thought to dominate iNKT cytokine
      production, a distinct subset of iNKT cells, expressing RORgammat and producing
      IL-17, has now been identified in both mice and humans. Although a role in
      pathogen and allergic responses has been assigned to the RORgammat(+) iNKT
      subset, factors controlling their development and function remain illusive. Here,
      we demonstrate that RORgammat(+) iNKT-cell differentiation obeys transforming
      growth factor-beta (TGF-beta) signaling control, different from that described
      for conventional iNKT cells. We reveal that TGF-beta signaling, and particularly
      its SMAD4-dependent pathway, is required for both the survival of RORgammat(+)
      iNKT cells during their development and IL-17 production at the periphery.
      Moreover, constitutive TGF-beta signaling in RORgammat(+) iNKT cells drives
      higher peripheral numbers and increased tissue distribution. Finally, we found
      that SMAD4-dependent TGF-beta signaling is mandatory for the peripheral expansion
      of the RORgammat(+) iNKT cells responding to inflammatory signals. Thus, this
      work demonstrates that both the development and responsiveness of the newly
      described IL-17-producing iNKT cell subset is under the control of a dedicated
      TGF-beta signaling pathway.

PMID- 22371887
TI  - Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical
      Hodgkin lymphoma.
AB  - In the present study, we evaluated the efficacy and safety of rituximab in
      combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine
      (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study,
      patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab
      375 mg/m(2) weekly for 6 weeks and standard ABVD for 6 cycles. The primary
      outcome was event-free survival (EFS) at 5 years. Eighty-five patients were
      enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months
      (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and
      overall survival rates were 83% and 96%, respectively. The 5-year EFS for
      patients with stage III/IV cHL was 82%. Furthermore, the 5-year EFS for patients
      with an International Prognostic Score of 0-2 was 88% and for those with a score
      of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse
      events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results
      demonstrate that the addition of rituximab to ABVD is safe and has a promising
      clinical activity in patients with advanced-stage cHL. These data are currently
      being confirmed in a multicenter randomized trial.

PMID- 22371888
TI  - Daptomycin versus vancomycin in a methicillin-resistant Staphylococcus aureus
      endophthalmitis rabbit model: bactericidal effect, safety, and ocular
      pharmacokinetics.
AB  - Staphylococcus aureus is a frequent cause of acute endophthalmitis, and infection
      with this virulent bacterium is often associated with a poor visual outcome. In
      this study, we investigated the bactericidal efficacy and the safety of
      intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum
      activity against Gram-positive bacteria, compared with those of intravitreal
      vancomycin (VAN) in a methicillin-resistant S. aureus endophthalmitis rabbit
      model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected
      eyes were also studied. Rabbits were randomly divided into three treatment groups
      (n = 8) and one untreated group (n = 4), to compare the effect of single
      intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1
      groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group).
      Vitreal aspirates were regularly collected and grading of ocular inflammation was
      regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the
      eyes were sterilized and the mean bacterial count presented a reduction of 1 log
      unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5%
      of eyes sterilized, respectively), with a 4-log-unit reduction of the mean
      bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to
      that in the VAN 1 group and was superior to that of the other regimens in
      limiting the ocular inflammation and preserving the architecture of the ocular
      structures (P < 0.05). The elimination half-life (t(1/2beta)) of daptomycin was
      independent of the administered dose (38.8 +/- 16.5 h and 40.9 +/- 6.7 h,
      respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than
      the t(1/2beta) of vancomycin (20.5 +/- 2.0 h for the VAN 1 group) (P < 0.05).
      This antibiotic could therefore be considered for the treatment of intraocular
      infections caused by Gram-positive bacteria.

PMID- 22371889
TI  - In vivo selection of moxifloxacin-resistant Clostridium difficile.

PMID- 22371890
TI  - Dosing regimen matters: the importance of early intervention and rapid attainment
      of the pharmacokinetic/pharmacodynamic target.
AB  - To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have
      focused on PK/PD relationships evaluated at steady-state drug concentrations.
      However, a concern with reliance upon steady-state drug concentrations is that it
      ignores events occurring while the pathogen is exposed to intermittent suboptimal
      systemic drug concentrations prior to the attainment of a steady state.
      Suboptimal (inadequate) exposure can produce amplification of resistant bacteria.
      This minireview provides an overview of published evidence supporting the
      positions that, in most situations, it is the exposure achieved during the first
      dose that is relevant for determining the therapeutic outcome of an infection,
      therapeutic intervention should be initiated as soon as possible to minimize the
      size of the bacterial burden at the infection site, and the duration of drug
      administration should be kept as brief as clinically appropriate to reduce the
      risk of selecting for resistant (or phenotypically nonresponsive) microbial
      strains. To support these recommendations, we briefly discuss data on inoculum
      effects, persister cells, and the concept of time within some defined mutation
      selection window.

PMID- 22371892
TI  - Chromosomal mutations responsible for fluoroquinolone resistance in Ureaplasma
      species in the United States.
AB  - We sequenced the full lengths of the gyrA, gyrB, parC, and parE genes in 13
      fluoroquinolone-resistant Ureaplasma isolates (levofloxacin MICs, 4 to 32 MUg/ml)
      and 10 susceptible isolates (MICs <= 2 MUg/ml). Mutations were detected in all
      resistant isolates but in none of the susceptible isolates. The most prevalent
      mutation was the S83L substitution in the ParC protein. No plasmid-mediated
      fluoroquinolone resistance genes were detected.

PMID- 22371891
TI  - Incidence and predictors of nephrotoxicity associated with intravenous colistin
      in overweight and obese patients.
AB  - Intravenous colistin is used to treat resistant Gram-negative infections and is
      associated with nephrotoxicity. In overweight and obese adults, a paucity of data
      exists regarding the incidence and predictors of such toxicity. A retrospective
      nested case-control study was performed over 35 months for patients receiving
      intravenous colistin for >= 72 h with a body mass index (BMI) of >= 25 kg/m(2).
      The objective was to investigate the incidence and predictors of nephrotoxicity.
      Severity of acute kidney injury was defined by RIFLE (risk, injury, failure,
      loss, and end-stage kidney disease) criteria. Dosing and mortality were
      secondarily investigated. Forty-two patients met the inclusion criteria, and 20
      (48%) developed nephrotoxicity. Patients with toxicity were in the risk (15%),
      injury (5%), and failure (80%) categories based on RIFLE criteria. A logistic
      regression model identified four predictors of colistin-associated
      nephrotoxicity: a BMI of >= 31.5 kg/m(2) (odds ratio [OR], 3.1; 95% confidence
      interval [CI], 1.15 to 8.35), diabetes (OR, 2.11; 95% CI, 0.84 to 5.29), the
      length of hospitalization in days prior to receipt of colistin (OR, 1.04; 95% CI,
      0.99 to 1.08), and age (OR, 1.08; 95% CI, 1.00 to 1.17). Among all of the
      patients, dosing based on the actual body weight and excessive dosing due to the
      use of the actual body weight were frequent at 64% and 92%, respectively. The 30
      day all-cause in-hospital mortality rate was 40% in the toxicity group and 14% in
      the nontoxicity group (P = 0.14). Patients receiving intravenous colistin should
      be monitored for nephrotoxicity, especially when the BMI exceeds 31.5 kg/m(2).
      Prospective, randomized, controlled trials are warranted to further examine
      nephrotoxicity incidence and predictors and appropriate dosing strategies in this
      population.

PMID- 22371893
TI  - Infrequent finding of metallo-beta-lactamase VIM-2 in carbapenem-resistant
      Pseudomonas aeruginosa strains from Croatia.
AB  - One hundred sixty-nine nonreplicate imipenem-resistant Pseudomonas aeruginosa
      strains isolated in a large hospital on the coastal region of Croatia were
      studied. The most active antibiotics were colistin and amikacin. Most of the
      isolates were multiresistant. The most prevalent serotype was O12, followed by
      O11. Six strains carried the bla(VIM-2) gene located in a novel class 1 integron
      composed in its variable part of the bla(VIM-2)-bla(oxa-10)-DeltaqacF-aacA4
      genes. Metallo-beta-lactamase-producing strains belonged to sequence types ST235
      and ST111.

PMID- 22371895
TI  - Expression of the resistance-nodulation-cell division pump AdeIJK in
      Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator.
AB  - Resistance-nodulation-division efflux system AdeIJK contributes to intrinsic
      resistance to various drug classes in Acinetobacter baumannii. By whole-genome
      sequencing, we have identified in clinical isolate BM4587 the adeN gene, located
      813 kbp upstream from adeIJK, which encodes a TetR transcriptional regulator. In
      one-step mutant BM4666 overexpressing adeIJK, the deletion of cytosine 582
      (C(582)) in the 3' portion of this gene was responsible for a frameshift mutation
      resulting in the deletion of the seven C-terminal residues. trans-Complementation
      of this BM4587 derivative with a plasmid expressing adeN restored antibiotic
      susceptibility to the host associated with the loss of adeJ overexpression. The
      inactivation of adeN in BM4587 led to a diminished susceptibility to antibiotics
      that are substrates for AdeIJK and to a 5-fold increase in adeJ expression. Taken
      together, these results indicate that AdeN represses AdeIJK expression.
      Quantitative reverse transcription-PCR (qRT-PCR) demonstrated that AdeN is
      constitutively expressed in BM4587 and does not regulate its own expression.
      Deletion of cytosine 582 and a 394-bp deletion of the 3' part of adeN were found
      in independent one-step adeIJK-overexpressing mutants selected from clinical
      isolates BM4667 and BM4651, respectively. The corresponding alterations were
      located in the alpha9 helix, which is known to be involved in dimerization, a
      process essential for the activity of TetR regulators. The adeN gene was detected
      in all of the 30 A. baumannii strains tested and in Acinetobacter calcoaceticus,
      Acinetobacter nosocomialis, and Acinetobacter pittii.

PMID- 22371894
TI  - Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV
      positive and healthy individuals.
AB  - The objectives of this study were to characterize raltegravir (RAL) population
      pharmacokinetics in HIV-positive (HIV(+)) and healthy individuals, identify
      influential factors, and search for new candidate genes involved in UDP
      glucuronosyltransferase (UGT)-mediated glucuronidation. The pharmacokinetic
      analysis was performed with NONMEM. Genetic association analysis was performed
      with PLINK using the relative bioavailability as the phenotype. Simulations were
      performed to compare once- and twice-daily regimens. A 2-compartment model with
      first-order absorption adequately described the data. Atazanavir, gender, and
      bilirubin levels influenced RAL relative bioavailability, which was 30% lower in
      HIV(+) than in healthy individuals. UGT1A9*3 was the only genetic variant
      possibly influencing RAL pharmacokinetics. The majority of RAL pharmacokinetic
      variability remains unexplained by genetic and nongenetic factors. Owing to the
      very large variability, trough drug levels might be very low under the standard
      dosing regimen, raising the question of a potential relevance of therapeutic drug
      monitoring of RAL in some situations.

PMID- 22371896
TI  - Daptomycin and tigecycline have broader effective dose ranges than vancomycin as
      prophylaxis against a Staphylococcus aureus surgical implant infection in mice.
AB  - Vancomycin is widely used for intravenous prophylaxis against surgical implant
      infections. However, it is unclear whether alternative antibiotics used to treat
      methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as
      prophylactic agents. The aim of this study was to compare the efficacies of
      vancomycin, daptomycin, and tigecycline as prophylactic therapy against a
      methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in
      mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of
      a surgically placed medical-grade metallic implant. The efficacies of low- versus
      high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and
      tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in
      vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation.
      High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions
      in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and
      tigecycline were more effective than low-dose vancomycin against the implant
      infection. In this mouse model of surgical implant MSSA or MRSA infection,
      daptomycin and tigecycline prophylaxis were effective over a broader dosage range
      than vancomycin. Future studies in humans will be required to determine whether
      these broader effective dose ranges for daptomycin and tigecycline in mice
      translate to improved efficacy in preventing surgical implant infections in
      clinical practice.

PMID- 22371897
TI  - Highly resistant Salmonella enterica serovar Typhi with a novel gyrA mutation
      raises questions about the long-term efficacy of older fluoroquinolones for
      treating typhoid fever.
AB  - As a consequence of multidrug resistance, clinicians are highly dependent on
      fluoroquinolones for treating the serious systemic infection typhoid fever. While
      reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is
      becoming ubiquitous, comprehensive resistance is exceptional. Here we report
      ofloxacin treatment failure in typhoidal patient infected with a novel, highly
      fluoroquinolone-resistant isolate of Salmonella enterica serovar Typhi. The
      isolation of this organism has serious implications for the long-term efficacy of
      ciprofloxacin and ofloxacin for typhoid treatment.

PMID- 22371898
TI  - No effect of a single supratherapeutic dose of lersivirine, a next-generation
      nonnucleoside reverse transcriptase inhibitor, on corrected QT interval in
      healthy subjects.
AB  - The objective of this study was to investigate the effect of a supratherapeutic
      dose of lersivirine (LRV) on corrected QT (QTc) interval using Fridericia's
      equation (QTcF) in healthy subjects. In this randomized, single-dose, placebo-
      and active-controlled 3-way crossover study, healthy adult males (n = 48) were
      randomized to receive LRV (2,400 mg), moxifloxacin (400 mg), or placebo for each
      treatment period. Triplicate 12-lead electrocardiogram measurements were
      performed, PK samples were collected, and vital signs were measured. Adverse
      event monitoring and safety laboratory testing were performed. All subjects were
      white (mean age, 39 years; body mass index [BMI], 25.6 kg/m(2)) and completed the
      study. Following LRV administration, the upper bound of the 90% confidence
      interval (CI) for time-matched adjusted mean differences to placebo QTcF at each
      time point postdose was below the regulatory threshold of 10 ms, satisfying the
      criteria for a negative thorough QT/QTc study. The highest upper bound of QTcF
      90% CI occurred at 6 h for LRV (3.32 ms; 90% CI, 1.47 to 5.17 ms). The study was
      deemed adequately sensitive as the lower bound of the 90% CI for the adjusted
      mean QTcF differences between moxifloxacin and placebo at the moxifloxacin
      historical T(max) of 3 h was >5 ms (15.29 ms; 90% CI, 13.44 to 17.14 ms). There
      was no statistically significant relationship between LRV exposure and placebo
      adjusted change from baseline QTcF or clinically significant changes in QRS
      complex, pulse rate (PR) interval, heart rate, or blood pressure. LRV (2,400 mg)
      did not prolong the QTcF interval, and no clinically relevant electrocardiogram
      or vital sign changes were observed in healthy subjects.

PMID- 22371899
TI  - rplC T460C identified as a dominant mutation in linezolid-resistant Mycobacterium
      tuberculosis strains.
AB  - The ribosomal L3 protein was identified as a novel target in linezolid (LZD)
      resistant Mycobacterium tuberculosis strains. Next-generation sequencing
      confirmed rplC T460C as the sole mutation in an LZD-resistant M. tuberculosis
      H37Rv strain selected in vitro. Sequencing analysis revealed the rplC T460C
      mutation in eight further LZD-resistant isolates (three in vitro-selected mutants
      and five patient isolates, including isolates from three different patients that
      developed LZD resistance during treatment) but in none of the susceptible control
      strains (n = 84).

PMID- 22371900
TI  - Quality assessment of U.S. marketplace vancomycin for injection products using
      high-resolution liquid chromatography-mass spectrometry and potency assays.
AB  - In response to a published concern about the potency and quality of generic
      vancomycin products, the United States Food and Drug Administration investigated
      a small sampling of the vancomycin products available in North America with
      regard to purity, content, and potency. To facilitate identification of
      impurities, a new liquid chromatography method was developed using high
      resolution mass spectrometry in addition to diode array detection to characterize
      impurities in several commercial products. Furthermore, a microbiological assay
      was utilized to link the analytical profiles with an in vitro potency. All
      products tested met the quality specifications outlined in the United States
      Pharmacopeia (USP) (vancomycin hydrochloride for injection monograph) for
      impurities and potency (USP, Vancomycin hydrochloride for injection. United
      States Pharmacopeia and National Formulary, vol USP 34-NF 29, 2011).

PMID- 22371901
TI  - Genomewide overexpression screen for fosfomycin resistance in Escherichia coli:
      MurA confers clinical resistance at low fitness cost.
AB  - To determine whether the overexpression of chromosomal genes can confer
      fosfomycin resistance, genomewide screening of a complete set of 5,272 plasmid
      expressed open reading frames of Escherichia coli (ASKA collection) was
      performed. Major results are that (i) no clinical level of resistance is achieved
      by overexpressing chromosomal genes, except murA; (ii) this level is reached at a
      low fitness cost; and (iii) this cost is much lower than that imposed by other
      mutations conferring fosfomycin resistance.

PMID- 22371902
TI  - Successful long-term treatment of cerebral nocardiosis with unexpectedly low
      doses of linezolid in an immunocompromised patient receiving complex polytherapy.
AB  - Cerebral nocardiosis is a severe infection that carries the highest mortality
      rate among all bacterial cerebral abscesses. We report on a case in an
      immunocompromised patient which was successfully treated with unexpectedly low
      doses of linezolid. Therapeutic drug monitoring was very helpful in highlighting
      issues of poor compliance and of drug-drug interactions.

PMID- 22371903
TI  - AA amyloid quantification in biopsy samples from the stomach.
AB  - Amyloidosis is usually diagnosed through the histological examination of biopsy
      samples. However, its quantitative evaluation can be difficult. In this study, we
      immunochemically measured amyloid A (AA) proteins in biopsy samples taken from
      the stomachs of patients with AA amyloidosis. Samples were treated with guanidine
      and were subjected to an enzyme immunoassay for serum amyloid A. The results were
      compared with histological findings. All patients who tested negative for amyloid
      deposits had low values that clearly distinguished them from amyloid-positive
      patients. Among the amyloid-positive patients, the AA values correlated
      significantly with histological findings. This method may be useful for the
      quantitative evaluation of AA amyloidosis.

PMID- 22371904
TI  - The relationship between serum neutrophil gelatinase-associated lipocalin and
      renal function in patients with vancomycin treatment.
AB  - Background Vancomycin is used for the treatment of resistant staphylococcal and
      enterococcal infections but is associated with nephrotoxicity. Neutrophil
      gelatinase-associated lipocalin (NGAL) was recently identified as a sensitive
      biomarker for acute kidney injury. Here, we aimed to investigate the usefulness
      of serum NGAL in monitoring patients undergoing vancomycin therapy.  Methods A
      total of 253 NGAL tests from 59 patients undergoing vancomycin therapy were
      evaluated. Patients with trough serum concentrations of vancomycin that exceeded
      20 ug/mL were included. Serum NGAL was measured using a commercially available
      ELISA kit, and other biochemical indicators including creatinine, leukocyte
      count, eGFR and C-reactive protein were assessed.  Results At the initiation of
      vancomycin treatment, serum creatinine level was 0.93 +/- 0.40 (mean +/- SD)
      mg/dL, NGAL was 341 +/- 354 mg/dL, leukocyte count was 10,750 +/- 7190 per uL and
      CRP level was high (10.8 +/- 9.3 mg/dL). About 49% of patients had an elevated
      leukocyte count, and all patients showed a high CRP level. Basal serum NGAL
      concentration in the patients with elevated leukocyte level (10,000/uL or higher)
      was higher compared to that in patients with normal leukocyte levels (mean +/-
      SD, 478 +/- 449 mg/dL vs. 176 +/- 101 mg/dL, p<0.001). A significant positive
      relationship was found between NGAL level and creatinine level in patients with
      normal basal leukocyte levels but not in those with higher leukocytes. 
      Conclusion The clinical usefulness of serum NGAL should be interpreted carefully
      when evaluating renal impairment in patients undergoing vancomycin treatment.

PMID- 22371905
TI  - Potential contribution of matrix metalloproteinase-9 (mmp-9) to cerebral
      vasospasm after experimental subarachnoid hemorrhage in rats.
AB  - This study investigated the possible involvement of matrix metalloproteinase 9
      (MMP-9) in cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rats.
      The CVS model was established by injection of fresh autologous nonheparinized
      arterial blood into the cisterna magna. Experiment 1 aimed to investigate the
      timecourse of the MMP-9 expression in the basilar artery after SAH. In Experiment
      2, we chose the maximum time point of vasospasm (Day 3) and assessed the effect
      of SB-3CT (a selective MMP- 9 inhibitor) on the regulation of cerebral vasospasm.
      The cross-sectional area of basilar artery was measured by H&E staining and the
      MMP-9 expression was assessed by immunohistochemistry analysis. The elevated
      expression of MMP-9 was detected in the basilar artery after SAH and peaked on
      day 3. After intracisternal administration of SB-3CT, the vasospasm was markedly
      attenuated after blood injection on day 3. Our results suggest that MMP-9 is
      increasingly expressed in a parallel time course to the development of cerebral
      vasospasm in this rat experimental model of SAH and that the administration of
      the specific MMP-9 inhibitor could prevent or reduce cerebral vasospasm caused by
      SAH.

PMID- 22371906
TI  - Sensitivity and specificity of bone marrow hemophagocytosis in hemophagocytic
      lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease
      characterized by abnormal activation of T-lymphocytes and macrophages. The
      diagnosis of HLH can be established if there is a family history of HLH, or
      evidence of genetic defects, or if 5 of 8 clinicopathologic criteria are
      fulfilled. This case-control study aimed to examine the extent of
      hemophagocytosis on the bone marrow examination of patients fulfilling diagnostic
      criteria for HLH. Hemophagocytosis in 6 bone marrow aspirates from 3 HLH patients
      was compared with 20 random control bone marrows. Macrophages with
      hemophagocytosis were counted using a Miller ocular disc in fields corresponding
      to 9,000 nucleated cells. Mean hemophagocytosis count in the HLH cases was
      estimated at 0.082% (range 0-0.31%), whereas in the controls it was 0.009% (range
      0-0.04%). The sensitivity of hemophagocytosis was 83% with a specificity of only
      60%. This demonstrates that rare hemophagocytosis can be seen in bone marrow
      aspirates from patients without a clinical diagnosis of HLH. It also shows that
      hemophagocytosis has too low a specificity to be a screening test for HLH. While
      the hemophagocytosis counts are significantly higher in HLH cases than in
      controls, overlap of the counts precludes using hemophagocytosis as a reliable
      indicator of HLH. A rise in the hemophagocytosis count threshold of 0.05-0.13%
      would increase the specificity to 100%. We suggest that the diagnostic scheme for
      HLH needs revision, and can be improved by addressing minimum hemophagocytosis
      count threshold.

PMID- 22371907
TI  - Genetic ablation of toll-like receptor 2 reduces secondary brain injury caused by
      cortical contusion in mice.
AB  - Previous studies have shown that Toll-like receptor 2 (TLR2) was up-regulated
      after traumatic brain injury (TBI), but the potential contribution of TLR2 to TBI
      still remains unclear. The present study investigated the role of TLR2 in
      modulating TBI-induced secondary brain injury in mice. Wild-type TLR2(+/+) and
      TLR2(-/-)-deficient mice were subjected to a moderately severe weight-drop impact
      head injury. Brain samples were extracted at 24 hours after trauma. We measured
      TLR2 by western blot; motor function by Grip test; brain edema by wet/dry method;
      cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) method; and IL-1beta, TNF-alpha and IL-6 by enzyme-linked
      immunosorbent assay (ELISA). We found the absence of TLR2 function in mice
      resulted in amelio-rating brain injury as shown by the reduced severity of
      neurological deficit, apoptosis, and brain edema at 24 hours after TBI, which was
      associated with the decreased expression of inflammatory cytokines such as tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin
      6 (IL-6), compared with their wild-type counterparts after TBI. In combination,
      these results suggest that TLR2 might play an important aggravating role in the
      pathogenesis of TBI-induced secondary brain injury, possibly by regulating
      inflammatory cytokines in the cortex.

PMID- 22371908
TI  - The effect of cherry sticks extract on the levels of glycoproteins in alloxan
      induced experimental diabetic mice.
AB  - This study was designed to evaluate the effect of ethanolic cherry sticks extract
      on the levels of glycoproteins in alloxan-induced diabetic mice. Forty-five adult
      male albino mice were divided equally into three groups: Group 1: control, Group
      2: diabetic mice, Group 3: diabetic mice treated with cherry sticks extract as
      well as to eighteen mice treated with cherry sticks extract only for toxicity
      test. All treatments were administered via an intragastric tube. Diabetes was
      induced in the mice of Group 3 by an intraperitoneal injection with 100 mg/kg
      body weight of alloxan. Oral administration of cherry sticks extract at a
      concentration of 250 mg/kg body weight for 15 days significantly reduced the
      levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as
      those of hexose, hexosamine, fucose, and sialic acid in the diabetic mice treated
      with the cherry sticks extract as compared to untreated diabetic mice, with no
      adverse effects in mice treated only with cherry sticks extract. In conclusion,
      cherry sticks extract proved to have a beneficial effect on the diabetic mice in
      this study. In light of these advantageous results, it is advisable to broaden
      the scale of use of cherry sticks extract in a trial to alleviate the adverse
      effects of diabetes.

PMID- 22371909
TI  - An improved flow cytometry-based natural killer cytotoxicity assay involving
      calcein AM staining of effector cells.
AB  - Several flow cytometric methods for measuring natural killer cell activity have
      been developed. Commonly used protocols involve the staining of target cells with
      various fluorescent dyes. However, these protocols are not applicable to certain
      experimental settings. Therefore, we used Calcein AM (CAM), which has been
      reported to be the most suitable dye for use in target cell staining protocols,
      as a means of developing an improved flow cytometry-based NK cytotoxicity assay
      involving effector cell staining. Peripheral blood mononuclear cells (PBMCs)
      isolated by gradient density centrifugation and expanded NK cells were used as
      effector cells. Cytotoxicity against K562 cells and several hematologic cancer
      cell lines was measured by a flow cytometry-based method using CAM and propidium
      iodide. The new assay was compared with a standard (51)Cr release assay (CRA) in
      terms of its ability to measure the cytotoxicity of NK cells in PBMCs and
      expanded NK cells against K562 cells. The optimal concentration of CAM for
      staining effector cells was 0.05 MUM, and CAM fluorescence intensity in effector
      cells was maintained for 4 hours. CAM staining had no significant effect on NK
      cell activity in human PBMCs or expanded NK cells. Comparison of the CRA and this
      new assay using K562 cells revealed a good correlation (PBMCs, r = 0.894;
      expanded NK cells, r = 0.887). Distinct separation between target tumor cells
      (Daudi, Raji, RPMI8226, U266, U937, and K562 cells) and CAM-stained PBMCs (E:T
      ratio, 12.5:1 to 50:1) or expanded NK cells (E:T ratio, 0.5 to 4:1) was observed
      after incubation for 1 or 4 hours. In summary, we successfully developed an
      effective flow cytometry-based assay for assessing the activity of NK cells in
      PBMCs and expanded NK cells against K562 cells and various types of hematologic
      cancer cells.

PMID- 22371910
TI  - Critical appraisal of air pouch infection model in rats.
AB  - The aim of this study was to assess the efficacy and pharmacokinetic profiles of
      gentamicin, vancomycin, and levofloxacin in a rat air pouch model, in which
      Staphylococcus aureus (ATCC 25293) was used as the test organism. Antibiotic
      treatments (i.p.) were started 1 hour after bacterial inoculation and continued
      for 5 days. Bacterial counts and antibiotic concentrations were determined in
      pouch exudates that were obtained on the 5th day of antibiotic treatment. The
      following observations were made: 1) The concentrations of gentamicin or
      vancomycin in the exudate were found to be below the detection limit. 2)
      Levofloxacin and ciprofloxacin exhibited a dose-dependent effect on bacterial
      counts in the exudate. 3) The antibacterial efficacy of levofloxacin was found to
      be enhanced when the total daily dose of 10 mg was divided into smaller parts.
      The present study also showed that the air pouch infection model was a valuable
      tool to assess the pharmacokinetic and pharmacodynamic properties of antibiotics.

PMID- 22371911
TI  - Procalcitonin levels within 48 hours after burn injury as a prognostic factor.
AB  - PURPOSE: This study was performed to evaluate the clinical significance of
      procalcitonin in burn patients and to investigate whether procalcitonin levels at
      admission can be a prognostic indicator for sepsis and mortality. MATERIALS AND
      METHODS: Between January 2009 and December 2010, procalcitonin levels in 175
      patients were tested within the first 48 hours after burn injury. Serum
      procalcitonin was measured using an enzyme-linked fluorescence assay. Mortality
      rates and positive culture rates of blood, wound, and sputum were evaluated among
      the subgroups divided by burn size, procalcitonin levels, and clinical prognosis.
      RESULTS: Positive blood culture and mortality rates correlated significantly with
      procalcitonin concentrations within the first 48 hours after burn injury. The
      area under the ROC curve for procalcitonin related to mortality was 0.844.
      Survival analysis revealed that the mortality rate was significantly higher in
      patients with procalcitonin concentrations >= 2 ng/mL than in patients with
      procalcitonin concentrations < 2 ng/mL (P < 0.001). Multivariate analysis
      demonstrated that procalcitonin was an independent prognostic factor for burn
      patients (Hazard ratio = 3.16, P = 0.001). CONCLUSIONS: Procalcitonin
      concentrations determined within the first 48 hours after burn injury can be a
      useful prognostic indicator for sepsis and mortality in burn patients.

PMID- 22371912
TI  - Clinical and genetic analysis of three Korean children with pyridoxine-dependent
      epilepsy.
AB  - Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that
      causes intractable seizures, especially in neonates and infants. Patients are
      typically resistant to typical antiepileptic drugs (AEDs) but respond
      dramatically to pyridoxine. Mutations in the ALDH7A1 gene are associated with the
      pathogenesis of PDE. Herein, we report the clinical phenotypes and disease
      causative mutations in the ALDH7A1 gene in three Korean patients with PDE. We
      reviewed the medical records, electroencephalography (EEG), brain magnetic
      resonance imaging (MRI) findings, and the results of molecular genetic tests for
      the patients who were diagnosed with PDE in our institution between Jan. 1996 and
      Dec. 2010. In all patients, the first seizures began during the first week of
      life. The seizures were not fully controlled with multiple AEDs, but disappeared
      immediately after administration of pyridoxine and returned after it was
      transiently discontinued. Before the use of pyridoxine, interictal EEGs showed
      multifocal epileptiform discharges, which became normalized with pyridoxine.
      Direct sequencing analyses revealed two mutant alleles in all three patients.
      Patient 1 was compound heterozygous with two different missense mutations,
      c.1061A>G (p.Y354C) and c.1232C>T (p.P411L). Patient 2 was homozygous for a
      missense mutation, c.1279G>C (p.E427Q). Patient 3 was compound heterozygous for
      two different missense mutations, c.1061A>G (p.Y354C) and c.1279G>C (p.E427Q),
      and her parents and younger brother were heterozygous carriers of each one of the
      mutations. All three mutations had not previously been reported. Herein, we
      report three Korean patients with three novel mutations who presented with PDE.

PMID- 22371913
TI  - Primary composite lymphoma of the larynx, composed of diffuse large B-cell
      lymphoma and peripheral T-cell lymphoma, not otherwise specified, presenting as
      left subglottic tracheal fistula, esophageal diverticulum, and neck abscess.
AB  - Primary laryngeal lymphoma occurs very rarely, accounting for far less than 1% of
      primary malignant laryngeal neoplasms. To the best of our knowledge, primary
      laryngeal composite lymphoma has not been reported in the literature. Herein, we
      report the first case of primary laryngeal composite lymphoma composed of diffuse
      large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise
      specified (PTCL, NOS), in a 43-year-old man. Of special interest is the patient's
      unique clinical presentation of left subglottic tracheal fistula, esophageal
      diverticulum, and neck abscess with no discrete mass identified. We describe the
      clinical and pathological characteristics of this case and review the literature.

PMID- 22371914
TI  - Cystic prostatic ductal adenocarcinoma: an unusual presentation and cytological
      diagnosis.
AB  - Prostatic ductal adenocarcinoma (PDA) is an uncommon histological variant of
      prostatic adenocarcinoma that may present clinically as a cystic mass [1-3]. We
      report a case of cystic PDA presenting as a cystic perirectal mass in a 61 year
      old male. Fine needle aspiration cytology showed malignant cells with round-oval
      to focally elongated nuclei, conspicuous nucleoli, and amphophilic cytoplasm with
      focal acinar formation. Tumor cells were positive for prostate-specific antigen;
      however, the cytology was non-specific for site of origin. The radical
      cystoprostatectomy specimen revealed the true site of origin and showed a cystic
      PDA adjacent to conventional prostatic acinar adenocarcinoma. Our objective is to
      describe the common cytological features of PDA and to analyze the differential
      diagnoses associated with cystic masses of the prostate.

PMID- 22371915
TI  - A Korean patient with Morquio B disease with a novel c.13_14insA mutation in the
      GLB1 gene.
AB  - Mutations in the GLB1 gene, which encodes acid beta-galactosidase, can result in
      two disease phenotypes: GM1-gangliosidosis (MIM #230500) and Morquio B disease
      (Mucopolysaccharidosis type IVB, MIM #253010). Morquio B disease occurs much more
      infrequently than GM1-gangliodosis and is characterized by severe skeletal
      manifestations (dysostosis multiplex) without central nervous system involvement.
      Here, we report the first known Korean patient with Morquio B disease. A 7-year
      old boy presented with severe progressive skeletal dysplasia including scoliosis,
      contractures of the elbows, xenu valgum, funnel chest, and trigger thumb
      requiring surgical intervention. The patient had normal neurological functions
      and mental status when evaluated by pediatric neurologists. The patient's urinary
      glycosaminoglycans, measured by the cetylpyridinium chloride (CPC) precipitation
      test, were 252.8 CPC unit/g creatinine (reference range < 175). Thin layer
      chromatography of urine showed a keratan sulfate band. Enzyme activity of beta
      galactosidase in leukocytes was 1.15 nmol/hr/mg protein (reference range 78.1
      117.7; 1-1.5% of normal). The patient had compound heterozygous mutations of the
      GLB1 gene: c.13_14insA (p.L5HfsX29), which was reported in a patient with
      infantile GM1 gangliosidosis with the near-complete absence of enzyme activity,
      and c.367G>A (p.G123R), which is a novel frame-shift mutation. In summary, we
      report the first known Korean patient with Morquio B disease and a novel mutation
      (c.13_14insA of GLB1).

PMID- 22371916
TI  - Nitric oxide and antioxidant status in head and neck carcinoma before and after
      radiotherapy.
AB  - OBJECTIVES: The mainstay of the treatment of head and neck squamous cell
      carcinoma (HNSCC) is radiotherapy, which acts by producing free radicals.
      Therefore, this study was planned to observe the effect of radiotherapy on
      oxidative stress in patients of HNSCC. METHODS: This study was conducted on 50
      histopathologically proven cases of HNSCC. The levels of nitric oxide,
      glutathione-S-transferase, and vitamin C were estimated colorimetrically before
      and after treatment in patients and in 30 age- and sex-matched healthy controls.
      The results were compared statistically. RESULTS: The levels of nitric oxide and
      glutathione-S-transferase were significantly higher in patents as compared to
      controls and increased significantly after treatment. Vitamin C levels were
      significantly lower in patients as compared to controls and decreased
      significantly after treatment. CONCLUSIONS: HNSCC leads to increased oxidative
      stress and treatment in the form of radiotherapy itself produces an accentuation
      of this stress.

PMID- 22371917
TI  - A Gly1609Arg missense mutation in the vWF gene in a Korean patient with von
      Willebrand disease type 2A.
AB  - We describe a case of a c.4825G>A (p.Gly1609Arg [Gly846Arg]) missense mutation in
      the gene encoding von Willebrand factor (vWF) in a Korean patient with von
      Willebrand disease (vWD) type 2A. The proband is a 37-year-old female who suffers
      from dysmenorrhea and menorrhagia. On laboratory testing, we found a low (0.01)
      vWF:RCo/Ag ratio, a decrease in high and intermediate molecular weight multimers
      from plasma, and abnormalities in the collagen binding capacity of plasma vWF,
      all of which were indicative of vWD type 2. Family studies revealed that her
      sister, son, and daughter also had a low vWF:RCo/ Ag ratio and a decrease in high
      molecular weight multimers from plasma. Genetic analyses showed that she and her
      three family members had the same heterozygous c.4825G>A (p.Gly1609Arg
      [Gly846Arg]) missense mutation. To our knowledge, this is the first report of the
      c.4825G>A (p.Gly1609Arg [Gly846Arg]) heterozygote mutation in Korean family
      members with vWD type 2A.

PMID- 22371918
TI  - A 56-year-old physician who underwent a PSA test.

PMID- 22371919
TI  - Initial coronary stent implantation with medical therapy vs medical therapy alone
      for stable coronary artery disease: meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Prior meta-analyses have yielded conflicting results regarding the
      outcomes of treatment of stable coronary artery disease (CAD) with initial
      percutaneous coronary intervention (PCI) vs medical therapy. However, most of the
      studies in prior systematic reviews used balloon angioplasty as well as medical
      therapies that do not reflect current interventional or medical practices. We
      therefore performed a meta-analysis of all randomized clinical trials comparing
      initial coronary stent implantation with medical therapy to determine the effect
      on death, nonfatal myocardial infarction (MI), unplanned revascularization, and
      persistent angina. METHODS: Prospective randomized trials were identified by
      searches of the MEDLINE database from 1970 to September 2011. Trials in which
      stents were used in less than 50% of PCI procedures were excluded. Data were
      extracted from each study, and summary odds ratios (ORs) were obtained using a
      random effects model. RESULTS: Eight trials enrolling 7229 patients were
      identified. Three trials enrolled stable patients after MI, whereas 5 studies
      enrolled patients with stable angina and/or ischemia on stress testing. Mean
      weighted follow-up was 4.3 years. The respective event rates for death with stent
      implantation and medical therapy were 8.9% and 9.1% (OR, 0.98; 95% CI, 0.84
      1.16); for nonfatal MI, 8.9% and 8.1% (OR, 1.12; 95% CI, 0.93-1.34); for
      unplanned revascularization, 21.4% and 30.7% (OR, 0.78; 95% CI, 0.57-1.06); and
      for persistent angina, 29% and 33% (OR, 0.80; 95% CI, 0.60-1.05). CONCLUSION:
      Initial stent implantation for stable CAD shows no evidence of benefit compared
      with initial medical therapy for prevention of death, nonfatal MI, unplanned
      revascularization, or angina.

PMID- 22371920
TI  - Mounting evidence for lack of PCI benefit in stable ischemic heart disease : what
      more will it take to turn the tide of treatment?: comment on "initial coronary
      stent implantation with medical therapy vs medical therapy alone for stable
      coronary artery disease".

PMID- 22371921
TI  - Informed strategies for treating coronary disease: comment on "initial coronary
      stent implantation with medical therapy vs medical therapy alone for stable
      coronary artery disease".

PMID- 22371922
TI  - Assessing gait speed in acutely ill older patients admitted to an acute care for
      elders hospital unit.
AB  - BACKGROUND: Assessment of mobility in geriatric hospital units relies primarily
      on subjective observation or patient self-reports. We objectively examined the
      gait speed of hospitalized older patients. METHODS: Prospective study of 322
      patients 65 years or older admitted from the community to a geriatric hospital
      unit between March 2008 and October 2009. Associations of gait speed (in meters
      per second) and activities of daily living with length of stay and home discharge
      were examined in multivariable logistic and generalized linear regression models.
      RESULTS: In total, 206 of 322 patients completed the gait speed walk, with a mean
      gait speed of 0.53 m/s. A strong association was found between faster gait speed
      and shorter length of stay. Patients unable to complete the walk and patients
      having gait speeds of less than 0.40 m/s had significantly longer lengths of stay
      by 1.9 and 1.4 days, respectively, compared with patients having gait speeds of
      at least 0.60 m/s. Similarly, patients unable to complete the walk (odds ratio,
      0.03; 95% CI, 0.003-0.21) and patients having gait speeds of less than 0.40 m/s
      (odds ratio, 0.07; 95% CI, 0.001-0.63) had significantly decreased odds of home
      discharge compared with patients having gait speeds of at least 0.60 m/s.
      Activities of daily living were less robust than gait speed in discriminating the
      risk of length of stay or home discharge. CONCLUSIONS: Gait speed is a clinically
      relevant indicator of functional status and is associated with important
      geriatric health outcomes, including length of stay and home discharge. Gait
      speed could be used to complement information obtained by self-reported
      activities of daily living.

PMID- 22371923
TI  - Gait speed in hospitalized older people: comment on "assessing gait speed in
      acutely ill older patients admitted to an acute care for elders hospital unit".

PMID- 22371924
TI  - Grief: four-plus years past.

PMID- 22371925
TI  - The relationship between clinical benefit and receipt of curative therapy for
      prostate cancer.

PMID- 22371926
TI  - Increasing US rates of endocarditis with Staphylococcus aureus: 1999-2008.

PMID- 22371927
TI  - Improvement of primary dysmenorrhea caused by a single oral dose of vitamin D:
      results of a randomized, double-blind, placebo-controlled study.

PMID- 22371928
TI  - Vitamin d for menstrual and pain-related disorders in women: comment on
      "improvement of primary dysmenorrhea caused by a single oral dose of vitamin d".

PMID- 22371929
TI  - Hearing loss and falls among older adults in the United States.

PMID- 22371930
TI  - Prescription drug use and self-prescription among training physicians.

PMID- 22371931
TI  - Rhetorical techniques in contexts other than cardiac resynchronization therapy.

PMID- 22371932
TI  - Better care for patients with diabetes: e-medicine is the goal.

PMID- 22371933
TI  - A counterargument to encounter frequency and target achievement: measurement
      variability.

PMID- 22371934
TI  - Limitations of subgroup analyses in meta-analysis of cardiac resynchronization
      therapy by QRS duration.

PMID- 22371935
TI  - International benchmarking of cardiac surgical activity and outcomes.

PMID- 22371936
TI  - Timing of surgical closure of patent ductus arteriosus in preterm neonates?
AB  - A retrospective cohort study was conducted on 115 preterm neonates who underwent
      patent ductus arteriosus ligation after failure of medical treatment, at Chiang
      Mai University Hospital between January 2003 and December 2010. Two groups were
      defined: an early surgery group (39.1%) treated with surgical closure within 21
      days, and a late surgery group (60.9%) operated on >21 days after birth. There
      were significant differences between the 2 groups in terms of weight at surgery,
      birth weight, duration of intubation, ductal size, and preoperative indomethacin
      usage. The early surgery group had a longer intensive care unit stay, but
      differences in postoperative chronic lung disease, ductal size, and surfactant
      use were not significant. Babies with a low birth weight (<1,500 g) and those
      with a higher ductal gradient were more susceptible to chronic lung disease, but
      multivariate analysis showed no difference between early and late surgery
      patients in either early extubation or chronic lung disease. It was concluded
      that early patent ductus arteriosus ligation did not show more benefits than late
      surgery.

PMID- 22371937
TI  - Recombinant activated factor VII for hemorrhage after pediatric cardiac surgery.
AB  - Postoperative bleeding is a common complication after pediatric cardiac surgery.
      Use of recombinant activated factor VII for intractable hemorrhage after cardiac,
      pediatric, and neurosurgery has been shown to decrease postoperative bleeding,
      but data in children are limited. This retrospective study analyzed 20 children
      <15 years-old who underwent cardiac surgery and received recombinant activated
      factor VII for refractory postoperative hemorrhage. All patients underwent
      mediastinal reexploration before recombinant activated factor VII was
      administered as a bolus dose over 2-3 min as rescue therapy. If no significant
      decrease in chest tube drainage was observed, the dose was repeated after an
      interval of at least 2 h. The median dose of recombinant activated factor VII
      administered per bleeding episode was 83.33 MUg.kg(-1) (range, 72.47-87.50
      MUg.kg(-1)), and the dose per patient was 154.16 MUg.kg(-1) (range, 93.06-180.52
      MUg.kg(-1)). The median number of doses found to be effective in these children
      was 1.76. There were significant decreases in mediastinal chest tube drainage and
      the volume of packed red blood cells, platelet concentrates, and cryoprecipitate
      administered after recombinant activated factor VII. No complications were
      observed during the therapy.

PMID- 22371938
TI  - Early outcomes of chordal reconstruction for posterior mitral leaflet prolapse.
AB  - We retrospectively reviewed 16 patients (7 men and 9 women, aged 36 to 77 years)
      who underwent mitral valve repair with chordal reconstruction for isolated
      posterior mitral leaflet prolapse. Preoperative echocardiography demonstrated
      moderate mitral regurgitation in 1, and severe regurgitation in 15. We routinely
      used expanded polytetrafluoroethylene sutures as artificial chords, and ring
      annuloplasty was performed in all cases (mean ring size, 30 +/- 2 mm). After
      implanting the ring, the length of the artificial chords was adjusted repeatedly
      using saline solution. Early postoperative echocardiography at 7.1 +/- 1.1 days
      after surgery showed mitral regurgitation grades reduced to none or trivial in
      15/16 patients. One required reoperation for recurrent mitral regurgitation 1.5
      years after surgery. In the other patients, intermediate-term echocardiography at
      9.1 +/- 10.1 months after surgery demonstrated that residual mitral regurgitation
      was less than mild. We concluded that chordal reconstruction is an effective and
      highly reproducible procedure for the repair of isolated posterior mitral leaflet
      prolapse. Artificial chords for the posterior mitral leaflet should not be too
      long, to avoid systolic anterior motion or recurrent mitral regurgitation after
      surgery.

PMID- 22371939
TI  - Framingham risk-based survival of non-small-cell lung cancer.
AB  - This study was undertaken to determine whether the Framingham cardiovascular risk
      prediction model can identify patients who will have reduced 5-year survival
      after resection for primary lung cancer. The Framingham risk model for predicting
      cardiovascular death rates in a 5-year period was calculated for 1,981 patients
      undergoing resection for non-small-cell lung cancer. Receiver operator curve
      analysis was performed to determine a cutoff with regard to Framingham risk, and
      this was utilized to construct Kaplan-Meier survival curves for stages I, II, and
      III. Cox regression analysis was used to determine factors significantly
      affecting long-term survival. The Framingham risk model predicted that 0.015% to
      26.7 % (mean, 5.2%) of our patients would die over a 5-year period. Univariate
      analysis revealed the Framingham score as being significant for stages I and II,
      but not III. Cox regression analysis demonstrated age, body mass index,
      pneumonectomy, stage I, stage III, stage IV, and Framingham score were all
      significant determinants of 5-year survival. Framingham-based cardiovascular risk
      prediction in patients undergoing resection for non-small-cell lung cancer stages
      I and II defined a group with significantly worse 5-year survival.

PMID- 22371940
TI  - Upregulation of APE/ref-1 in recurrence stage I, non small cell lung cancer.
AB  - Lung cancer, the leading cause of cancer-related death, still lacks reliable
      biomarkers. Apurinic/apyrimidinic endonuclease 1/Ref-1 is a multifunctional
      protein involved in the base excision repair of DNA damaged by oxidative stress
      or alkylating compounds, as well as in the regulation of multiple transcription
      factors. To validate apurinic/apyrimidinic endonuclease 1/Ref-1 as a biomarker
      for prediction of lung cancer recurrence, we studied 42 patients who received
      curative resection and mediastinal lymph node dissection for stage I non-small
      cell lung cancer. They were divided into 2 groups based on recurrence, and
      compared by immunohistochemistry staining of paraffin-embedded tissues and
      Western blot analysis. Immunohistochemical staining showed a significant
      difference between the cytoplasm and nucleus in patients who had a recurrence
      compared to those with nonrecurrent adenocarcinoma. In Western blot analysis, the
      recurrent adenocarcinoma group showed increased expression of
      apurinic/apyrimidinic endonuclease 1/Ref-1 in cytoplasm, nucleus, and in total.
      This indicates that apurinic/apyrimidinic endonuclease 1/Ref-1 is unregulated in
      recurrent stage I adenocarcinoma. For clinical application as a prognostic marker
      for non-small-cell lung cancer, further investigation into the role of
      apurinic/apyrimidinic endonuclease 1/Ref-1 in carcinogenesis is needed in an
      expanded prospective study.

PMID- 22371941
TI  - Phosphodiesterase-5 inhibitor and rat lung ischemia-reperfusion injury.
AB  - To explore the protective effect of the phosphodiesterase-5 inhibitor,
      sildenafil, on lung ischemia-reperfusion injury, 30 rats were randomly divided
      into 3 groups of 10: a sham-operated group A, a lung ischemia-reperfusion injury
      group B, and a sildenafil preconditioned group C. A 0.1% sildenafil solution was
      administrated orally 2 h before establishing an in-vivo lung ischemia-reperfusion
      model in group C; 0.9% normal saline solution was used in the controls. The lung
      wet-to-dry ratio, malondialdehyde content, myeloperoxidase and nitric oxide
      synthase activity in groups B and C were significant higher than those in group
      A, while the partial pressure of oxygen in arterial blood and cyclic guanosine
      3',5'-monophosphate content in groups B and C were significant lower than those
      in group A. Compared to group B, lung wet/dry ratio, malondialdehyde content,
      myeloperoxidase and nitric oxide synthase activity in group C were significantly
      lower, while arterial O(2) and cyclic guanosine-3',5'-monophosphate content in
      group C were significantly higher. The expected histological and cytological
      changes were significantly alleviated in group C. Oral preconditioning with
      sildenafil prevented rat lung ischemia-reperfusion injury and improved pulmonary
      function. The mechanisms of this effect might be prevention of cyclic guanosine
      monophosphate degradation and inhibition of nitric oxide synthase activity.

PMID- 22371942
TI  - Thymoma and myasthenia gravis: clinical aspects and prognosis.
AB  - Myasthenia gravis is present in a significant proportion of patients with
      thymoma. We investigated particular features of the clinical behavior of thymoma
      and its relationship to myasthenia in a retrospective study of 79 patients who
      underwent thymectomy for thymoma during the last 20 years. The presence of
      myasthenia gravis, Masaoka stage, World Health Organization histotype, myasthenia
      response, and survival were analyzed. The mean age of the patients was 56.1 +/-
      12.4 years, and 39 had myasthenia gravis. A significantly higher proportion of
      patients with myasthenia was found in B2 and B3 histotypes compared to A, AB, and
      B1. Among myasthenic patients, 33.3% had no response, 50% had a partial response,
      and 16.7% achieved complete remission. During the follow-up period, 16 (21.1%)
      patients died. Mean survival was 4.8 +/- 1.4 years for patients with no
      myasthenia response, whereas those with a partial or complete myasthenia response
      had significantly better survival.

PMID- 22371943
TI  - Surgical treatment for tracheobronchial carcinoid tumors: a 16-year experience.
AB  - We conducted a 16-year retrospective review of 31 cases of tracheobronchial
      carcinoid tumors treated in our institution between 1995 and 2011, to determine
      their characteristic features and outcome of management. There were 12 men and 19
      women. The most common presenting symptoms were cough and hemoptysis (71%) with a
      mean duration of 4 years. Preoperative bronchoscopy confirmed the diagnosis in
      80% of patients. Right-sided tumors accounted for 60% of cases. Most tumors arose
      from the mainstem bronchi. Histologic analysis revealed typical carcinoids in 28
      cases and atypical carcinoids in 3. Surgical treatment was mainly radical
      resection (pneumonectomy in 19 patients). A parenchymal-preserving surgery
      (sleeve resection of left main bronchus and end-to-end anastomosis) was only
      possible in 2 cases. Mediastinal lymph nodes were involved in 30% of cases. Most
      patients had widespread extraluminal extension. Follow-up revealed recurrence in
      one patient. No deaths were recorded, and complications were mainly atelectasis
      and air leak. Radical resection remains the mainstay of surgical management of
      bronchial carcinoids in cases of late presentation with destroyed and
      bronchiectatic distal pulmonary parenchyma. Parenchymal-preserving surgery should
      only be carried out when indicated.

PMID- 22371944
TI  - Relapsing infective endocarditis following closure of ventricular septal defect.
AB  - An 8-year-old boy who had undergone Dacron patch closure of a ventricular septal
      defect 5 years earlier, was admitted with relapsing methicillin-resistant
      Staphylococcus aureus infective endocarditis and lung abscesses. Echocardiography
      indicated vegetation attached to the tricuspid valve and the Dacron patch. The
      infected patch was replaced with glutaraldehyde-treated autologous pericardium.
      He was discharged uneventfully and has been well for 4 years, without signs of
      infection.

PMID- 22371945
TI  - Catastrophic late mitral bioprosthetic thrombosis.
AB  - Although clinically significant bioprosthetic valve thrombosis is rare, it should
      be considered a possible cause of valve dysfunction when there is an increasing
      transvalvular pressure gradient after anticoagulation is terminated. We describe
      a rare case of bioprosthetic mitral thrombosis in a 77-year-old woman 2 years
      after valve replacement and a maze procedure.

PMID- 22371946
TI  - Simple and quick repair of cardiac rupture due to blunt chest trauma.
AB  - Atrial rupture following blunt chest trauma carries a high mortality rate. It can
      be difficult to maintain hemodynamic stability and control massive bleeding due
      to poor visualization. We describe a case in which bleeding control was obtained
      simply and effectively using a Satinsky clamp, allowing repair of atrial rupture
      without the use of cardiopulmonary bypass.

PMID- 22371947
TI  - Large sinus of Valsalva aneurysm causing myocardial infarction.
AB  - A 41-year-old man was urgently admitted with sudden onset of chest pain.
      Emergency coronary angiography revealed a large aneurysm of the sinus of Valsalva
      and reduced blood flow in the left coronary artery. A modified Bentall operation
      and coronary artery bypass were performed successfully. A large sinus of Valsalva
      aneurysm should be regarded as a critical problem that could cause coronary
      insufficiency.

PMID- 22371948
TI  - Aortic root and hemiarch replacement in osteogenesis imperfecta.
AB  - We describe a case of osteogenesis imperfecta in a 52-year-old man who underwent
      successful repair of aortic root dilatation and aortic valve insufficiency, using
      a bioprosthetic aortic valve anastomosed to an interposition graft.

PMID- 22371949
TI  - Malignant granular cell tumor of the posterior mediastinum with dissemination.
AB  - A 66-year-old man presented with severe back pain. Imaging studies revealed a
      well-circumscribed mass in the left posterior mediastinum. Because of pleural
      dissemination observed at thoracotomy, palliative resection was performed to
      relieve his back pain. Histologically, the tumor was composed of cells with large
      eosinophilic and granular cytoplasm, which were strongly positive for S-100.
      Mediastinal malignant granular cell tumor with pleural dissemination is extremely
      unusual.

PMID- 22371950
TI  - Cardiophrenic angle lymph node metastasis from a fallopian primary tumor.
AB  - Isolated cardiophrenic angle node metastases are relatively rare, as are primary
      fallopian tube carcinomas. We describe a case of a cardiophrenic angle node
      metastasis from such a tumor, with no peritoneal involvement. A 52-year-old
      woman, who had been previously diagnosed with fallopian tube carcinoma, was
      referred with a right cardiophrenic angle mass. A thoracoscopic resection was
      performed. The pathological diagnosis was lymph node metastasis from the primary
      lesion.

PMID- 22371951
TI  - Thoracoscopy-assisted removal of left ventricular thrombus via minithoracotomy.
AB  - A left ventricular thrombus was successfully removed after broad anterior
      myocardial infarction in a 58-year-old woman, using video-assisted thoracoscopy
      via minimally invasive port access. Through a right minithoracotomy, a left
      ventricular thrombus behind the papillary muscles and trabeculation were
      completely visualized with the aid of thoracoscopy, and removed without
      difficulty. This approach seems to be a useful alternative to a left
      ventriculotomy, avoiding the resultant compromised left ventricular function.

PMID- 22371952
TI  - Typical carcinoid arising in mature teratoma of anterior mediastinum.
AB  - Teratoma is the second most common mediastinal neoplasm, but malignant
      transformation in mature teratomas is uncommon at both gonadal and extragonadal
      sites. A 35-year-old woman presented with an anterior mediastinal mass. Computed
      tomography suggested a teratoma. Meticulous pathological examination helped in
      detecting a neuroendocrine neoplasm (carcinoid) within the mature teratoma.
      Malignant transformation in a teratoma is difficult to diagnose on clinical and
      radiological assessment; histopathology is essential to detect the malignant
      nature of these neoplasms.

PMID- 22371953
TI  - Descending necrotizing mediastinitis and thoracic cellulitis due to varicella.
AB  - A 22-year-old man with varicella had associated cervical enlargement, right upper
      thoracic anterior and suprascapular cellulitis, and mediastinitis. A
      tracheostomy, right posterolateral thoracotomy, cervicotomy, and upper thoracic
      fasciotomy were performed 14 h after admission, draining purulent exudates from
      all sites. The patient was discharged on postoperative day 22.

PMID- 22371954
TI  - Compression of the trachea by intrathoracic vagus nerve schwannoma.

PMID- 22371955
TI  - Intimal sarcoma of the inferior vena cava with extension to the right atrium.

PMID- 22371956
TI  - Diagnostic dilemma of mitral annulus calcification imitating intracardiac tumor.

PMID- 22371957
TI  - Myocardial ischemia due to congenital hypoplastic left coronary cusp in adult.

PMID- 22371958
TI  - Tunneling technique for anatomical positioning of aortoaxillary bypass graft.
AB  - A technique for anatomical positioning of a synthetic aortoaxillary bypass tube
      graft is described. A tunnel is created with the help of a Roberts clamp and
      intercostal tube drain. There is no need to open the pleura because the graft is
      tunneled parallel to the subclavian vessels outside the chest cavity.

PMID- 22371960
TI  - High visibility enforcement demonstration programs in Connecticut and New York
      reduce hand-held phone use.

PMID- 22371961
TI  - Tough art and microbial drama.

PMID- 22371962
TI  - New studies cast dark cloud over air pollution.

PMID- 22371963
TI  - India probes corruption in flagship health programme.

PMID- 22371964
TI  - A first step in bringing typhoid fever out of the closet.

PMID- 22371965
TI  - Spectacular anatomy: plastination and salutary dread.

PMID- 22371967
TI  - Proceedings of a Bridge to a Consensus on Hepatocellular Carcinoma Management.
      The 2nd Asia Pacific Primary Liver Cancer Expert Meeting. July 1-3, 2011, Osaka,
      Japan.

PMID- 22371966
TI  - Proceedings of the International Workshop on Monte Carlo Computational Methods in
      Radiation Track Simulation and Applications in Physical, Biological, and Medical
      Sciences. 2010 Stockholm, Sweden.

PMID- 22371968
TI  - Freeze-dried human serum albumin improves the adherence and proliferation of
      mesenchymal stem cells on mineralized human bone allografts.
AB  - Mineralized scaffolds are widely used as bone grafts with the assumption that
      bone marrow derived cells colonize and remodel them. This process is slow and
      often unreliable so we aimed to improve the biocompatibility of bone grafts by
      pre-seeding them with human mesenchymal stem cells from either bone marrow or
      dental pulp. Under standard cell culture conditions very low number of seeded
      cells remained on the surface of freeze-dried human or bovine bone graft or
      hydroxyapatite. Coating the scaffolds with fibronectin or collagen improved
      seeding efficiency but the cells failed to grow on the surface until the 18th
      day. In contrast, human albumin was a very potent facilitator of both seeding and
      proliferation on allografts which was further improved by culturing in a rotating
      bioreactor. Electron microscopy revealed that cells do not form a monolayer but
      span the pores, emphasizing the importance of pore size and microstructure.
      Albumin coated bone chips were able to unite a rat femoral segmental defect,
      while uncoated ones did not. Micro-hardness measurements confirmed that albumin
      coating does not influence the physical characteristics of the scaffold, so it is
      possible to introduce albumin coating into the manufacturing process of
      lyophilized bone allografts.

PMID- 22371969
TI  - miRNA expression profile during osteogenic differentiation of human adipose
      derived stem cells.
AB  - Human adipose-derived stem cells (hADSC) are capable of differentiating into an
      osteogenic lineage. It is believed that microRNAs (miRNAs) play important roles
      in regulating this osteogenic differentiation of human adipose-derived cells,
      although its molecular mechanism remains unclear. We investigated the miRNA
      expression profile during osteogenic differentiation of hADSCs, and assessed the
      roles of involved miRNAs during the osteogenic differentiation. We obtained and
      cultured human adipose-derived stems cells from donors who underwent elective
      liposuction or other abdominal surgery at our institution. miRNA expression
      profiles pre- and post-osteogenic induction were obtained using microarray essay,
      and differently expressed miRNAs were verified using quantitative real-time
      polymerase chain reaction (qRT-PCR). The expression of osteogenic proteins was
      detected using an enzyme-linked immunosorbent assay. Putative targets of the
      miRNAs were predicted using online software MiRanda, TargetScan, and miRBase.
      Eight miRNAs were found differently expressed pre- and post-osteogenic induction,
      among which four miRNAs (miR-17, miR-20a, miR-20b, and miR-106a) were up
      regulated and four miRNAs (miR-31, miR-125a-5p, miR-125b, and miR-193a) were down
      regulated. qRT-PCR analysis further confirmed the results. Predicted target genes
      of the differentially expressed miRNAs based on the overlap from three public
      prediction algorithms: MiRanda, TargetScan, and miRBase Target have the known
      functions of regulating stem cell osteogenic differentiation, self-renewal,
      signal transduction, and cell cycle control. We identified a group of miRNAs that
      may play important roles in regulating hADSC cell differentiation toward an
      osteoblast lineage. Further study of these miRNAs may elucidate the mechanism of
      hADSC differentiation into adipose tissue, and thus provide basis for tissue
      engineering.

PMID- 22371970
TI  - Restraint of spreading-dependent activation of polymorphonuclear leukocyte NADPH
      oxidase in an acidified environment.
AB  - Elucidation of the mechanisms by which environmental pH affects or regulates the
      functions of polymorphonuclear leukocytes (PMNs) is important because severe
      acidification of the microenvironment often prevails at sites of inflammation
      where they act in host defense. In the present study, we investigated the effect
      of an acidic environment on spreading-dependent activation of O2- -producing
      NADPH oxidase in PMNs. We found that PMNs underwent spreading spontaneously over
      type I collagen and plastic surfaces at both neutral and acidic pH, although
      spreading over fibrinogen surfaces, for which cellular stimulation with H2O2 is
      required, was inhibited by acidic pH. At acidic pH, however, PMNs were unable to
      undergo spreading-dependent production of O2-. Pharmacological experiments showed
      that p38 mitogen-activated protein kinase (MAPK) was involved in the signaling
      pathways mediating the spreading-dependent activation of NADPH oxidase, and that
      its spreading-dependent phosphorylation of Thr-180 and Tyr-182, a hallmark of
      activation, was impaired at acidic pH. Furthermore, the inhibition by acidic pH
      of O2- production as well as p38 MAPK phosphorylation subsequent to spreading
      induction was reversible; environmental neutralization and acidification after
      induction of spreading at acidic and neutral pH, respectively, up- and down
      regulated the two phenomena. Acidic pH did not affect the O2- production activity
      of NADPH oxidase pre-activated by phorbol 12-myristate 13-acetate (PMA). These
      results suggest that, in PMNs, the p38 MAPK-mediated signaling pathway functions
      as a pH-sensing regulator of spreading-dependent NADPH oxidase activation.

PMID- 22371972
TI  - Special issue dedicated to Professor G. Berrie Edwards.

PMID- 22371973
TI  - The hinge region of the scaffolding protein of cell contacts, zonula occludens
      protein 1, regulates interacting with various signaling proteins.
AB  - Zonula occludens protein 1 (ZO-1) is a ubiquitous scaffolding protein, but it is
      unknown why it functions in very different cellular contacts. We hypothesized
      that a specific segment, the unique hinge region, can be bound by very different
      regulatory proteins. Using surface plasmon resonance spectroscopy and binding
      assays to peptide libraries, we show, for the first time, that the hinge region
      directly interacts with disparate signal elements such as G-proteins alpha 12 and
      alpha i2, the regulator of G-protein signaling 5, multifunctional signaling
      protein ahnak1, and L-type Ca2+-channel beta-2-subunit. The novel binding
      proteins specifically bound to a coiled coil-helix predicted in the hinge region
      of ZO-. The interactions were modulated by phosphorylation in the hinge helix.
      Activation of the G-proteins influenced their association to ZO-1. In colon
      cells, G alpha i2 and ZO-1 were associated, as shown by coimmunoprecipitation.
      After cotransfection in kidney cells, G alpha i2 barely colocalized with ZO-1;
      the colocalization coefficient was significantly increased when epinephrine
      activated G-protein signaling. In conclusion, proteins with different regulatory
      potential adhere to and influence cellular functions of ZO-proteins, and the
      interactions can be modulated via its hinge region and/or the binding proteins.

PMID- 22371971
TI  - Calcineurin serves in the circadian output pathway to regulate the daily rhythm
      of L-type voltage-gated calcium channels in the retina.
AB  - The L-type voltage-gated calcium channels (L-VGCCs) in avian retinal cone
      photoreceptors are under circadian control, in which the protein expression of
      the alpha1 subunits and the current density are greater at night than during the
      day. Both Ras-mitogen-activated protein kinase (MAPK) and Ras
      phosphatidylionositol 3 kinase-protein kinase B (PI3K-AKT) signaling pathways are
      part of the circadian output that regulate the L-VGCC rhythm, while cAMP
      dependent signaling is further upstream of Ras to regulate the circadian outputs
      in photoreceptors. However, there are missing links between cAMP-dependent
      signaling and Ras in the circadian output regulation of L-VGCCs. In this study,
      we report that calcineurin, a Ca2+/calmodulin-dependent serine (ser)/threonine
      (thr) phosphatase, participates in the circadian output pathway to regulate L
      VGCCs through modulating both Ras-MAPK and Ras-PI3K-AKT signaling. The activity
      of calcineurin, but not its protein expression, was under circadian regulation.
      Application of a calcineurin inhibitor, FK-506 or cyclosporine A, reduced the L
      VGCC current density at night with a corresponding decrease in L-VGCCalpha1D
      protein expression, but the circadian rhythm of L-VGCCalpha1D mRNA levels were
      not affected. Inhibition of calcineurin further reduced the phosphorylation of
      ERK and AKT (at thr 308) and inhibited the activation of Ras, but inhibitors of
      MAPK or PI3K signaling did not affect the circadian rhythm of calcineurin
      activity. However, inhibition of adenylate cyclase significantly dampened the
      circadian rhythm of calcineurin activity. These results suggest that calcineurin
      is upstream of MAPK and PI3K-AKT but downstream of cAMP in the circadian
      regulation of L-VGCCs.

PMID- 22371974
TI  - Proceedings of the Sixth International Conference on Protein kinase CK2,
      September 7-10, 2010, Cologne, Germany.

PMID- 22371975
TI  - Proceedings of the 14th European Winter Conference on Plasma Spectrochemistry,
      January 30-February 4, 2011, Zaragoza, Spain.

PMID- 22371977
TI  - 'European approach' to arc flash risk.
AB  - DuPont claims that electrical arc, and the resulting "arc flash", are among the
      deadliest, least understood hazards of electricity", and can potentially occur in
      many industrial and other applications, including hospital plant rooms. Technical
      and engineering personnel from DuPont Engineering Technology, DuPont Personal
      Protection, and external independent experts, have thus collaborated to develop
      "a European approach to electrical arc risk assessment". The resulting free
      online resource, the DuPont Arc-Guide, sets out key steps to minimise serious arc
      flash incident risk, and details a range of optional, paid-for tailored risk
      assessment services, and an accompanying secure web portal, offering more in
      depth guidance on this important, but apparently often overlooked, issue. HEJ
      editor Jonathan Baillie reports.

PMID- 22371978
TI  - A call for 'direction, clarity, and leadership'.
AB  - How the NHS can transform itself into a healthcare system equipped to meet
      current and future challenges--an ageing population, patients demanding an equal
      say with doctors on their treatment, a shift towards more care provision at home,
      and the radical plans proposed for GP commissioning consortia in the Health and
      Social Care Bill, all against a backdrop where public healthcare funding looks
      set to remain largely static for at least the next 3-5 years, was the theme of an
      impassioned keynote address by former Health Secretary and Labour MP for
      Darlington, Alan Milburn, at the recent Future Health & CareExpo conference and
      exhibition in London. HEJ editor Jonathan Baillie reports.

PMID- 22371979
TI  - Stories, skulls, and colonial collections.
AB  - The essay explores the hypothesis of colonial collecting processes involving the
      active addition of the colonial context and historical past to museum objects
      through the production of short stories. It examines the emergent historicity of
      collections through a focus on the "histories" that museum workers and colonial
      agents have been attaching to scientific collections of human skulls. Drawing on
      the notions of collection trajectory and historiographical work, it offers an
      alternative perspective from which to approach the creation of singular histories
      and individual archives for objects in collections.

PMID- 22371980
TI  - William Gibson's paternity test.
AB  - Contemporary culture views DNA through a strange temporal logic: on the one hand,
      technologies of DNA identification and sequencing testify to fundamental
      transformations in the way we understand biology, anthropology, law, and medicine
      we live in "the DNA age"; and on the other, these technologies have revealed as
      much about the past as they have about the present or future, gesturing backwards
      to scenes of conception, crime, and evolutionary branching. The essay shows how
      this double temporal logic operates within William Gibson's electronic poem
      Agrippa. It concludes that the poem's stanzas form a metaphorical DNA fingerprint
      that reveals Gibson's life to be, paradoxically, a novel repetition of his
      father's and grandfather's lives.

PMID- 22371981
TI  - Magnetic Resonance Imaging (MRI) as mirror and portrait: MRI configurations
      between science and the arts.
AB  - The essay examines the configuration of magnetic resonance imaging (MRI) in the
      scientific laboratory and in selected artworks. By drawing upon fieldwork
      undertaken in MRI labs and artists' ateliers, I argue that MRI has a "look" in
      the same way that the portrait has-that is, it has the capacity of being
      performative, thus resisting its being regarded as a transparent window onto the
      self. As will be shown, the look of MRI is acoustic more than visual, for it is
      based on the aural components of the examination, rather than on MRI images
      alone.

PMID- 22371982
TI  - Amateur knowledge: public art and citizen science.
AB  - The science studies literatures on amateurs and citizen science have remained
      largely unconnected despite similarities between the two categories. The essay
      connects amateur knowledge and citizen science through examples from public art.
      Through an analysis of the use of the term "amateur" by contemporary artists
      working to engage the public in critiques of science, connections in the ideals
      of democratic knowledge making by amateurs and citizen scientists are further
      explored.

PMID- 22371983
TI  - Deciphering the language of nature: cryptography, secrecy, and alterity in
      Francis Bacon.
AB  - The essay argues that Francis Bacon's considerations of parables and cryptography
      reflect larger interpretative concerns of his natural philosophic project. Bacon
      describes nature as having a language distinct from those of God and man, and, in
      so doing, establishes a central problem of his natural philosophy-namely, how can
      the language of nature be accessed through scientific representation? Ultimately,
      Bacon's solution relies on a theory of differential and duplicitous signs that
      conceal within them the hidden voice of nature, which is best recognized in the
      natural forms of efficient causality. The "alphabet of nature"-those tables of
      natural occurrences-consequently plays a central role in his program, as it
      renders nature's language susceptible to a process and decryption that mirrors
      the model of the bilateral cipher. It is argued that while the writing of Bacon's
      natural philosophy strives for literality, its investigative process preserves a
      space for alterity within scientific representation, that is made accessible to
      those with the interpretative key.

PMID- 22371984
TI  - The dilemma of the Rio+20 Summit.

PMID- 22371985
TI  - Interview of Dr. Ramesh Bilimagga in conversation with Dr. Sapna Gupta.

PMID- 22371986
TI  - Proposed career pathway for clinical academic general dental practitioners.

PMID- 22371987
TI  - [Didn't it matter to him absolutely?: Juan Vilanova and the controversy about
      tertiary man].
AB  - During the founding period of palaeoanthropology, the postulate about tertiary
      age of humankind was an outstanding subject. First proposals were based on
      supposed proofs about ancient lithical industry (eoliths). Some discoveries of
      human fossil remains complicated that issue, because they were dated as pliocene
      or oldest. This controversy about so-called "tertiary man" soon arrived to Spain.
      Juan Vilanova y Piera, palaeontologist and professor at Madrid, dealt with it
      from an antievolutionist point of view. When a human fossil skeleton, included in
      the Botet's collections, with several apparently primitive traits arrived to
      Valencia from Argentina, Vilanova got reasserted and exposed his ideas about this
      question more intensely.

PMID- 22371988
TI  - [Odon de Buen: forty-five years of commitment to the university].
AB  - The aragonese naturalist Odon de Buen y del Cos for twenty-two annual academic
      courses professor of natural history at the University of Barcelona and for
      twenty-three of the University of Madrid. Strong supporter of Darwin's
      evolutionary theory, experimental work in the field and laboratory, in this paper
      puts the value of their efforts, as an educator, to popularize the natural
      sciences and thus separated from the concerns, superstition and fanaticism, which
      they were basic reasons of the moral and material backwardness in which Spain was
      found.

PMID- 22371989
TI  - Gianotti-Crosti syndrome associated with hepatitis A and influenza vaccination.

PMID- 22371990
TI  - Pedunculated melanoma.

PMID- 22371991
TI  - JDD: celebrating 10 years of publishing excellence.

PMID- 22371992
TI  - Clarification from the CoC, NPCR, SEER technical workgroup.

PMID- 22371993
TI  - A middle class in the making: the negotiation of power and status at Bath's early
      Gregorian general infirmary, c. 1739-65.

PMID- 22371994
TI  - Raising the bar: what is your strategy for the 21st century?

PMID- 22371995
TI  - The importance of learning collaborative stage coding.

PMID- 22371996
TI  - Street disorders, surveillance and shame: regulating behavior in the public
      spaces of the late Victorian British town.

PMID- 22371998
TI  - The new Cancer Program Standards pilot project, 2011.

PMID- 22371999
TI  - [Shadows of the great victory].

PMID- 22372002
TI  - Child and adolescent psychiatry.

PMID- 22372000
TI  - [Supplying the Soviet population at the turn of the    1920's-30's].

PMID- 22372003
TI  - Trends in retail clinic use among the commercially insured.

PMID- 22372004
TI  - Nephrology.

PMID- 22372005
TI  - Neonatal-perinatal medicine.

PMID- 22372006
TI  - Balloon kyphoplasty.

PMID- 22372007
TI  - [The pharmaceutical industry in the industrial chemical group: the National Union
      of Chemical-Pharmaceutical Laboratories (1919-1936)].
AB  - The pharmaceutical industry associations, as it happened with other businesses,
      had a significant rise during the dictatorship of Primo de Rivera and II
      Republic. The 'Camara Nacional de Industrias Quimicas', in Barcelona, represented
      the national chemical industry to its ultimate assimilation by the 'Organizacion
      Sindical' in 1939. In this association, matters relating to pharmaceutical
      products -- which we will especially deal with in this work -- were managed by
      the 'Union Nacional de Laboratorios Quimico-Farmaceuticos', which defended the
      interests of pharmaceutical companies in the presence of government authorities,
      using the resources and mechanisms also managed by business pressure groups. The
      inclusion of industrial pharmacy in the Chemical lobby separated the
      pharmaceutical industry from traditional exercise and its corporate environment.
      this created ups and downs, conflicts of interests and finally, love and hate
      relationships with their colleagues of the pharmacy work placement and, of
      course, with the association that represented them: the 'Union Farmaceutica
      Nacional'.

PMID- 22372008
TI  - [To God through science. Natural theology in Francoism].
AB  - In Spain, during Franco's dictatorship (1939-1975) the teaching and divulgation
      of science were subordinated to the Catholic religion and many books defended a
      theistic and creationistic point of view of biology that accepted a literal
      interpretation of the Book of Genesis and denied the theory of evolution,
      especially as it relates to human origin. This article is devoted to the main
      books and characteristics of this way of thinking which reproduced arguments and
      metaphors of the pre-Darwinian natural theology, arguing that nature was ruled by
      God and living organisms were the results of his design.

PMID- 22372009
TI  - [Social-sanitary situation in Maranon's work in the context of the fight against
      infectious diseases].
AB  - Gregorio Maranon y Posadillo (1887-1960), played a leading role in the birth of
      endocrinology in Spain as is well known. However, his medical work included other
      important and significant fields. Thus, it was especially in the 1910s and 1920s,
      when Maranon dealt with the social-sanitary situation in madrid probably due to
      his professional attachment to the treatment of several infectious diseases and
      epidemic outbreaks. Actually, since 1911 onwards, he was in charge of the wards
      of infectious diseases in the Hospital General de Madrid where he had the
      opportunity of treating an important number of patients suffering from this type
      of pathology and, as a consequence, in the following years he published several
      articles in medical journals and presented in the Royal Academy of Medicine in
      Spain, some reports on infectious diseases and the Spanish health and social
      conditions at the time. This paper try to analyze this field of Maranon's social
      and scientific activity.

PMID- 22372010
TI  - One RN makes a difference It's as simple as ...

PMID- 22372011
TI  - Data bits. Put more pep in your step.

PMID- 22372012
TI  - Transforming a RN to BSN program to an on-line delivery format.

PMID- 22372013
TI  - Community cardiovascular care: a service learning project designed to reduce risk
      for cardiovascular disease.

PMID- 22372014
TI  - Blast lung injury.
AB  - Blast lung injury is an increasing problem for UK forces in Afghanistan, but is
      not a new phenomenon, with evidence that it has been increasing in incidence over
      the last century. Management is conservative, but there are newer therapies that
      may play a role in the future management of this condition.

PMID- 22372015
TI  - Common training injuries concerning potential Royal Marine applicants.

PMID- 22372016
TI  - The management of hand injuries in a role 2 enhanced or role 3 facility: Part 1.

PMID- 22372017
TI  - Case discussion:to treat or not to treat?

PMID- 22372018
TI  - The characteristics of pure tone audiograms in a sample of Royal Marines after
      Operation Herrick 9.

PMID- 22372019
TI  - Sickness and injury in the Navy medical officer's report after Jutland.

PMID- 22372020
TI  - Spontaneous oesophageal rupture.

PMID- 22372021
TI  - Medically unexplained symptoms--a perspective from general practitioners in the
      developing world.
AB  - OBJECTIVES: In this study, we explored the attitudes toward Medically Unexplained
      Symptoms (MUS) of 500 general practitioners (GPs) in Karachi, Pakistan. Using a
      questionnaire previously developed by Reid et al. (2001), we aimed to investigate
      whether GPs' attitudes toward medically unexplained symptoms are similar to those
      of GPs in the developed world. METHODS: Five hundred GPs on the database of
      primary care centers at the Pakistan Institute of Learning and Living in Karachi
      were all sent a covering letter explaining the purpose of the survey with a case
      vignette, a questionnaire, and a stamped addressed envelope. One month later, non
      respondents received a telephone call from an investigator to remind them of the
      study. RESULTS: Of the 429 respondents, 68.5% (294) were male and 31.5% (135)
      female. Although 80.2% of respondents felt that the main role of GPs was to
      provide support and reassurance, 76.9% of respondents also agreed that GPs had a
      role in referring patients with MUS for further investigations to identify a
      cause. Two hundred and four (47.55%) respondents agreed that somatization was
      useful concept, only 146 (34.03%) felt that there was effective treatment for it.
      CONCLUSION: For the most part, Pakistani GPs' attitudes toward MUS are not very
      different to those of their counterparts in the West. Both agree that the GP has
      an important role in providing reassurance and counseling. However, our survey
      also shows that Pakistani GPs are less likely to place emphasis on an underlying
      psychiatric diagnosis and tend to focus on looking for an underlying physical
      cause.

PMID- 22372022
TI  - The relationship between religious attendance and blood pressure: the HUNT Study,
      Norway.
AB  - OBJECTIVE: Research from the United States shows a possible relationship between
      religious attendance (RA) and blood pressure (BP). The religious context in the
      United States differs widely from Scandinavia. The aim was, therefore, to test
      whether the relationship between RA and BP is specific to the religious culture
      in the United States or whether a similar relationship exists between RA and BP
      in a Norwegian context. DESIGN AND METHOD: Data from the Nord-Trondelag Health
      Study's third wave, HUNT 3 (2006-08), was used. The associations between RA and
      diastolic (DBP) and systolic (SBP) blood pressure in women (n = 20,066) and men
      (n = 15,898) were investigated in a cross-sectional study using multiple
      regression analyses. RESULTS: Mean DBP for women/men was 71.0 mmHg/76.7 mmHg.
      Mean SBP was 128.5 mmHg/134.0 mmHg; 39.1%/42.8% of women/men never attended
      religious services, 3.8%/3.4% attended more than 3x/month. The bivariate
      associations were statistically significant between RA and SBP in both genders
      and women's DBP but not men's DBP. After adjustment, inverse associations between
      RA and DBP/SBP for both genders were found. The RA-DBP relationship (p < 0.001)
      demonstrated a gradient in effect for both genders, with increasing RA associated
      with decreasing DBP, with 1.50/1.67 mmHg lower in women/men respectively in those
      attending more than 3x/month, 0.87/1.16 mmHg lower in those attending 1-3x/month,
      and 0.49/0.10 mmHg less in those attending 1-6x/6 months. Differences in RA-SBP
      (p < 0.05) were 2.12/1.71 mmHg, 0.30/0.11 mmHg, and 0.58/0.63 mmHg, respectively.
      CONCLUSION: In a large population-based survey in Norway, RA was associated with
      lower DBP and SBP after adjusting for relevant variables.

PMID- 22372023
TI  - Correlations between psychological symptoms and social relationships among
      medical undergraduates in Anhui Province of China.
AB  - OBJECTIVES: To assess the prevalence of psychological symptoms (depression,
      anxiety) among Chinese medical students and to find the possible relationships
      between psychological symptoms and social relationships. METHODS: A sample of
      10,140 medical students was investigated with a structured questionnaire, that
      included the Beck Depression Inventory, Beck Anxiety Inventory, Social Support
      Rating Scale, and Family APGAR Index (adaptability, partnership, growth,
      affection, resolve). RESULTS: The present study revealed that 16.8% of the
      medical students suffered from depressive symptoms and 14.1% from anxiety
      symptoms. Female students were more likely to have anxiety, the second-year
      students had higher levels of psychological symptoms than the first-year
      students. Likewise, significant differences were found among college,
      satisfaction of specialty, and economic condition of the family in anxiety and
      depression symptoms. Social support, family function, and all dimensions were
      significantly negatively associated with depression and anxiety symptoms.
      Multivariable ordinal logistic regression showed that less social support, poor
      family function, the second-year students, and unsatisfactory specialty were
      associated with more psychological symptoms, after adjusting the effects of sex,
      age, and college. CONCLUSIONS: Medical students have a relatively high level of
      depression and anxiety symptoms. These findings support the hypothesis that if
      medical students are better supported and cared for, negative psychosocial
      consequences might be prevented or at least reduced.

PMID- 22372024
TI  - A multicenter study of bipolar disorder among emergency department patients in
      Latin-American countries.
AB  - OBJECTIVE: This multicenter study estimated the prevalence of bipolar disorder
      (BPD) among emergency department (ED) patients in Latin America. METHODS: To
      identify patients with BPD, a combination of DSM IV-criteria interview and the
      Mood Disorder Questionnaire (MDQ) was used. Data from 1,505 patients from
      hospitals in Argentina, Brazil, Chile, Colombia, and Mexico was analyzed.
      RESULTS: The prevalence ofBPD in this sample was 5.2% (95% CI = 4.5% to 6.9%).
      The mean age was 37 years (response rate of 83.0%). Compared to non-BPD patients,
      BPD patients were more likely to report asthma (16.7% vs. 9%), thyroid problems
      (12.8% vs. 5.8%), seizures (23.1% vs. 3.0%), obesity (39.7% vs. 26.9%), alcohol
      abuse (30.8% vs. 10.0%), attention deficit hyperactivity disorders (50.0% vs.
      12.0%), depression (81.6% vs. 45.7%), obsessive compulsive disorder (20.1% vs.
      3.0%), panic disorders (23.1% vs. 12.3%), phobic disorders (11.2% vs. 3.1%), and
      any anxiety disorder (82.1 % vs. 41.8%; all p < or = 0.05). Suicidal plans and
      attempts were also significant higher in the bipolar group (11.5% vs. 2.8% and
      10.3% vs. 1.8% respectively). Multivariate analysis identified ADHD, depression,
      alcohol abuse, anxiety disorder, and last month suicide plans and attempts to be
      independently associated with BPD. CONCLUSION: Our study supports that BPD is
      prevalent in ED in Latin-American countries and that comorbidity is the rule, not
      the exception. Patients presenting at ED with irritability, anxiety, pressure
      speech, euphoria, with suicidal tendencies, involved in risky behaviors, alcohol
      abuse, dependence or those with history of mental health hospitalization in the
      past 12 months must be assessed for comorbid BPD.

PMID- 22372025
TI  - Identification and treatment of depression in minority populations.
AB  - Depression is a common condition, representing close to 6% of visits to primary
      care providers. Although minorities are more likely to have chronic depression,
      they are more likely to be incorrectly diagnosed and less likely to receive
      treatment when compared to the mainstream population. Screening and appropriate
      treatment within primary care is recommended in clinical practices that have
      systems in place to assure accurate diagnosis, effective treatment, and follow
      up. This recommendation is especially relevant for treatment of minority
      populations, as they are more likely to seek care for mental health problems from
      primary care providers rather than specialists. A number of self-report screening
      tools that simplify screening are available. Treatment modalities that are
      supported by evidence are psychotherapy, prescription medications, and
      electroconvulsive therapy for severe depression. Selective serotonin reuptake
      inhibitors (SSRIs) have become the cornerstone of therapy for depression since
      the Food and Drug Administration (FDA) approval of fluoxetine in 1987. No
      substantial differences in efficacy of SSRIs have been found, although data
      suggest differences with respect to onset of action and adverse effects that may
      be relevant in the choice of one medicine over another. Common side effects of
      serotonin reuptake inhibitors include nausea, diarrhea, insomnia, somnolence and
      dizziness, akathisia, and sexual dysfunction. While most of these symptoms tend
      to subside within several weeks of use, sexual dysfunction appears to be a long
      term side effect that typically reverses within a few days after discontinuation
      of the causative medication. Selective norepinephrine reuptake inhibitors
      (SNRIs), bupropion, mirtazapine, and tricyclic antidepressants (TCAs) are other
      commonly used medications. Complementary and alternative treatments, such as St.
      John's wort (Hypericum perforatum), exercise, acupuncture, music therapy, and
      relaxation, have limited data supporting their efficacy.

PMID- 22372026
TI  - Elevated serum cholesterol levels in women with premenstrual dysphoric disorder.
AB  - OBJECTIVES: To study the association of premenstrual serum total cholesterol
      level (TC) with premenstrual dysphoric disorder (PMDD). METHOD: The premenstrual
      serum cholesterol levels of 34 patients with PMDD and 20 normal controls were
      measured, and the rates ofhypercholesterolemia in the 2 groups were compared.
      RESULTS: The mean of the premenstrual cholesterol level of the study group was
      180.82 +/- 34.47 mg/dL, while that of the control group was 162.45 +/- 21.29
      mg/dL (t = 2.152, df = 52, p = 0.036). The prevalence of premenstrual
      hypercholesterolemia (serum total cholesterol > 200 mg/dL) was 23.53% (8/34) in
      the PMDD group and zero in the normal control group (chi-square = 5.524, df = 1,
      p = 0.019). CONCLUSION: The results showed elevated premenstrual serum
      cholesterol in PMDD and implied a new direction of research to further explore
      the etiology of PMDD. It is suggested that the pathophysiology of premenstrual
      dysphoric disorder may be similar to that of anxiety disorders.

PMID- 22372027
TI  - Assessment of Suny Upstate Medical University's child telepsychiatry consultation
      program.
AB  - OBJECTIVES: The project assesses the child telepsychiatry services provided by
      SUNY Upstate psychiatrists to several county mental health clinics in central New
      York State. METHOD: Data for 45 patients was extracted from pre-consultation
      forms completed by the referring clinic and postconsultation summaries completed
      by the Upstate psychiatrists that occurred between July 13, 2009 and May 12,
      2010. The study identified characteristics of patients for whom telepsychiatry
      consultations were sought, why they were sought, and reviewed recommended changes
      in therapy and medication provided by the telepsychiatry consultant. RESULTS:
      Analysis of the data showed that there was a large variation in patient
      characteristics such as age (from age 3 to 17), current living situation, and
      psychological symptoms. In addition to a family history of mental illness (80%),
      the most common symptoms were physical aggression (60.0%), defiant/oppositional
      behavior (57.8%), and attentional problems (55.6%). The most common reason for
      referral was diagnostic clarification (67%). The child telepsychiatrist
      recommended a change in medication for most (80.8%) of the patients who were on
      medications, and to begin medications for most (63.2%) who were not receiving
      medication at the time of consult. Further, the telepsychiatrist often
      recommended the addition of family therapy (71.1%) and counseling at school
      (17.8%). CONCLUSION: The child telepsychiatric program at Upstate seemed
      effective. It reached a large variety of children with significant mental
      disorders. The consultants provided diagnostic clarification and recommended
      modification of treatment for most. However, this assessment is limited as
      examined as it did not include follow-up information on whether consultant
      recommendations were followed and, if they were, whether they were effective.

PMID- 22372028
TI  - Privatization of hospitals: meeting divergent interests.
AB  - The United States, Germany, and the United Kingdom are experiencing a trend
      toward the privatization of hospitals--most frequently involving poorly
      positioned facilities that need: additional capital for replacement of plant and
      equipment; improved management systems to reduce the number of their nondirect
      patient care employees; and an aggressive physician recruitment effort. A number
      of these institutions might have been otherwise shut down, resulting in the loss
      of good paying jobs; however, these closures would have reduced the nation's
      total health care expenditures. The acquisition in the United States and Germany
      by investor-owned hospital corporations of major teaching institutions suggests
      that the for-profits have become an integral part of their country's health care
      delivery system. Privatization now even occurs within the egalitarian British
      National Health Service with the availability of private medical insurance,
      private hospitals, and private beds in public hospitals being managed by investor
      owned groups. Being acquired by a for-profit is often a means to secure needed
      capital and is politically less fractious than closing down a marginally needed
      government-sponsored or a not-for-profit facility.

PMID- 22372029
TI  - The role of non-financial performance measures in predicting hospital financial
      performance: the case of for-profit system hospitals.
AB  - Non-financial measures have found increasing acceptance in the business world-
      however, their application in the health care industry remains limited. The
      purpose of this article is to understand the influence of non-financial measures
      (efficiency, productivity, and quality) on the financial performance of for
      profit system hospitals. The sample consists of 499 for-profit system hospitals
      in the United States from 1999 to 2002. Data analyzed include the American
      Hospital Association's Annual Survey, Medicare Cost Reports, Joint Commission's
      quality scores, and the Centers for Medicare & Medicaid Services' Hospital Case
      Mix Index. Dependent variables consist of financial measures (operating and total
      margins), while independent variables include measures of efficiency,
      productivity, and quality. Our results suggest the influence of non-financial
      performance measures on financial performance; occupancy rate positively
      influences financial performance while greater labor intensity may have negative
      implications for financial performance. In addition, we show that quality
      positively influences financial performance thereby offering a potential business
      case for quality. This result has important managerial and policy implications as
      it may incentivize capital and human resource investments required to improve
      hospital quality of care.

PMID- 22372030
TI  - Cash holdings of not-for-profit hospitals.
AB  - Many not-for-profit (NFP) hospitals hold substantial cash reserves. Using a
      national sample of 608 NFP hospitals over the period 1996-1999, we related
      theories of cash holdings to NFP hospitals to develop a conceptual framework for
      understanding cash holdings. We tested whether these hospitals differentially
      managed operating and strategic cash with respect to establishing target balances
      and investigated motivations for holding cash. NFP hospitals actively targeted
      levels of operating cash, but did not target strategic cash balances. Strategic
      cash balances were positively related to profitability and growth in assets, but
      negatively associated with the use of debt.

PMID- 22372031
TI  - Comparing pre-gap and gap behaviors for Medicare beneficiaries in a Medicare
      managed care plan.
AB  - OBJECTIVE: To examine the impact of the coverage gap on pharmacy use,
      expenditures, and out-of-pocket costs for Medicare managed care beneficiaries
      before and after reaching the gap. STUDY DESIGN: A longitudinal comparison of
      behaviors for beneficiaries with non-gap coverage before and after reaching the
      gap. METHODS: Prescription drug use and expenditures were assessed for Medicare
      beneficiaries who reached the gap, including subsets with one of four chronic
      disorders (congestive heart failure (CHF), diabetes, dyslipidemia, or
      hypertension). Differences in pre- and post-prescription use were calculated
      using generalized estimating equations. Time until the end and start of the gap
      was estimated using a Cox proportional hazards model. Expenditure data were
      estimated using bootstrap methods. RESULTS: Roughly a quarter (27.1 percent) of
      patients reached the gap in 2006, of whom 3.6 percent passed through the gap. The
      most prevalent disease state was hypertension (58.5 percent). Beneficiaries took
      an average of 8.1 months to reach the gap. Patients <65 years (HR = 1.42, 95% CI
      = 1.29 - 1.56) and those with diabetes (HR = 1.19, 95% CI = 1.12 - 1.27) were
      more likely to reach the gap sooner as compared to older beneficiaries (aged 65
      to 74) and those without diabetes. These individuals were more likely to pass
      through the gap as well. Beneficiaries faced a 60.7 percent increase in out-of
      pocket expenditures in the gap phase. Brand-name medication use decreased by 9.3
      percent, while generic medication use increased by 7.4 percent. For chronic
      conditions, however, over 90 percent of individuals continued brand-name
      medication use in the gap. CONCLUSIONS: Our findings suggest that, in general,
      beneficiaries take lower-cost generics while in the gap. However, taking brand
      name medications is the predominant behavior for beneficiaries with chronic
      diseases. Health care reform provisions that close the gap over the next ten
      years may facilitate continuity of medication use while in the gap.

PMID- 22372032
TI  - The push to increase the use of EHR technology by hospitals and physicians in the
      United States through the HITECH Act and the Medicare incentive program.
AB  - This article reviews key health care spending and electronic health records (EHR)
      statistics in the United States (Section II); highlights positive and negative
      aspects of EHR technology (Sections III and IV); briefly reviews the passage of
      the Health Information Technology for Economic and Clinical Health Act (HITECH)
      (Section V); discusses the rule passed by the Office of the National Coordinator
      for Health Information Technology (ONCHIT) and to implement the goals of HITECH
      (Section VI); discusses the rule passed by the Centers for Medicare & Medicaid
      Services (CMS) to implement the goals of HITECH and focuses on significant
      requirements of the Medicare incentive program rule as it applies to hospitals
      and physicians (Section VII); and finally, concludes by highlighting certain
      issues that have been raised regarding the goals of HITECH (Section VIII).

PMID- 22372033
TI  - Reporting intellectual capital in health care organizations: specifics, lessons
      learned, and future research perspectives.
AB  - This article analyzes the concept of intellectual capital (IC) in the health
      sector sphere by studying the case of a major nonprofit research organization in
      this sector, which has for some time been publishing IC reports. In the last few
      years, health care organizations have been the object of great attention in the
      implementation and transfer of managerial models and tools; however, there is
      still a lack of attention paid to the strategic management of IC as a fundamental
      resource for supporting and enhancing performance improvement dynamics. The main
      aim of this article is to examine the IC reporting model used by the Center of
      Molecular Medicine (CMM), a Swedish health organization which is an outstanding
      benchmark in reporting its IC. We also consider the specifics of IC reporting for
      health organizations, the lessons learned by analyzing CMM's IC reporting, and
      future perspectives for research.

PMID- 22372034
TI  - Working with words.

PMID- 22372035
TI  - Rare encounter.

PMID- 22372036
TI  - Reframing a conversation.

PMID- 22372037
TI  - Too much information. Interview by Kim Kiser.

PMID- 22372038
TI  - What breaks the bond?

PMID- 22372039
TI  - Family medicine's fan club.

PMID- 22372040
TI  - MN Supreme Court rules on newborn screening samples.

PMID- 22372041
TI  - Improvement also applies to quality improvement.

PMID- 22372042
TI  - Doctor, what's the story?

PMID- 22372043
TI  - The end of the medical deity.

PMID- 22372044
TI  - Parallel worlds.

PMID- 22372045
TI  - Tackling a taboo.

PMID- 22372046
TI  - The new language of medicine.

PMID- 22372047
TI  - Inaccuracy in patient handoffs: discrepancies between resident-generated reports
      and the medical record.
AB  - A handoff is the transfer of a patient's care from one provider to another. It
      usually involves both a verbal and written exchange of information. Although
      written handoff sheets are critical to good patient care, there is little data on
      the quality of information they contain. We conducted a study to assess the
      accuracy of handoff sheets used in one Minneapolis internal medicine residency
      program. We compared the accuracy of information about code status, medication
      allergies, medications, and problems recorded on the handoff sheet with that in
      the patient's medical record. We found errors were common in resident handoff
      sheets. Only 83 (19%) of 428 handoff sheets contained no errors. The most common
      error was one of omission on the medication list (69% of the handoff sheets
      contained a medication omission). The percentage of patient handoff sheets with
      code-status errors was 5.7%, and the percentage with medication allergy errors
      was 2.8%. Important problems were omitted from the problem list in 22% of cases.

PMID- 22372048
TI  - Meeting the needs of Somali patients at the end of life.
AB  - Given the large number of Somali refugees living in Minnesota, it is likely that
      Minnesota physicians will encounter Somali patients, some of whom will have
      serious illnesses. Although our knowledge of Somali expectations about health
      care is growing, little has been written about the Somali people's views of
      treatment for life-threatening illnesses or their ideas about end-of-life care.
      After encountering a Somali man with advanced cancer in our practice, we
      attempted to learn about the Somali view of death and dying and the kind of
      treatment Somali patients might want during their final days. We share what we
      learned so that others might provide more culturally competent end-of-life care
      for Somali patients in the future.

PMID- 22372049
TI  - Whose best interest?
AB  - In the summer of 1910, William James Mayo, M.D., delivered the commencement
      address at Rush Medical College in Chicago. In his speech, he uttered words that
      have become the cornerstone of Mayo Clinic's model of care: "The best interest of
      the patient is the only interest to be considered, and in order that the sick may
      have the benefit of advancing knowledge, a union of forces is necessary." In this
      article, we reflect on issues raised by Mayo's speech that strike at the very
      heart of our professional identity and ask two questions: Is medicine's foremost
      concern the best interest of the patient? And has medicine really united over the
      last century in the service of patients?

PMID- 22372050
TI  - Talking to sexually abused children: tips for physicians.
AB  - A child who has been sexually abused typically is not going to be forthcoming
      about the abuse. Therefore, it can be difficult and time-consuming for a
      physician who suspects sexual abuse to get the child to disclose what is
      happening. This article reviews strategies that can help physicians establish a
      trusting relationship with a child that may enable them to speak openly about
      what is going on in their lives.

PMID- 22372051
TI  - [Should "welfare" medication be allowed back?].

PMID- 22372052
TI  - [Stay to the left].

PMID- 22372053
TI  - [Surveillance].

PMID- 22372054
TI  - [Exaggerated breed characteristics in dogs].
AB  - Dutch dog owners seem to be aware of bad dog breeding practices with regard to
      exaggerated breed characteristics that are detrimental to the dog's welfare. Yet
      they do not always look for these features when buying a dog. Most dog owners
      think that veterinarians could have an important role in preventing these
      exaggerated physical traits, by providing information about these traits and
      taking action in their capacity as veterinarian. Articles 36 and 55 of the Dutch
      GWWD (animal health and welfare law) provide opportunities to act against the
      breeding of dogs with exaggerated genetic traits.

PMID- 22372055
TI  - [The contribution of pathology in the clinical diagnosis of cutaneous mast cell
      tumors in the dog].

PMID- 22372056
TI  - [Ovulation in dogs determined by measuring progesterone].

PMID- 22372057
TI  - [Laboratory fish-, crustaceans-, and shellfish diseases is looking for
      collaboration].

PMID- 22372058
TI  - [Words as medicine].

PMID- 22372059
TI  - ['Protected veterinarian takes his responsibility'].

PMID- 22372060
TI  - [Antibiotics on the human-veterinary borderline].

PMID- 22372061
TI  - ['The art is to directly take a good x-ray'].

PMID- 22372062
TI  - [Large differences in salaries for non-practicing veterinarians].

PMID- 22372063
TI  - [The world wide horse practice].

PMID- 22372064
TI  - [Gifts from the pharmaceutical industry to veterinarians is bound to rules].

PMID- 22372065
TI  - [Veterinarian should reinforce the role as port keeper].

PMID- 22372066
TI  - [Opinion: new therapy to dry off one mammae quarter?].

PMID- 22372067
TI  - [Working together on occupational zoonoses].

PMID- 22372068
TI  - [Reaction to the proteinuria with bolus].

PMID- 22372069
TI  - [Stroke--an expensive public health issue in Finland].
AB  - Of the Finnish population, 1.5% has hada stroke. Since the 1970's, the mortality
      of patients with a stroke has been reduced by half, but still one fifth of the
      patients succumb within 3 months of their stroke. The average lifetime healthcare
      costs after a stroke are 86,300 Euros per patient. Of this sum, two thirds, i.e.
      60,000 Euros, are directly due to stroke, one third due to other diseases. The
      sum spent annually in the treatment of stroke patients in Finland is 7%, i.e. 1.1
      Billion Euros, of total healthcare costs.

PMID- 22372071
TI  - [Life-threatening infection after varicose vein surgery].
AB  - Necrotizing fascitis is a rare but life-threatening soft tissue infection
      difficult to diagnose at early stage. We describe two patient cases, in which the
      patients developed a severe necrotizing soft tissue infection after varicose vein
      surgery. A quick and sufficiently radical surgical treatment is the most
      significant factor improving the prognosis. All surgical procedures may result in
      rare but severe complications, which should, however, be taken into account when
      assessing procedural indications and risks.

PMID- 22372070
TI  - [Hemolytic disease of the newborn has not vanished from Finland--routine
      protection of RhD negative mothers during pregnancy is justifiable].
AB  - Prophylaxis of RhD negative mothers with anti-D immunoglobulin after childbirth
      is the most important procedure reducing the immunization of the mother and the
      risk of severe hemolytic disease of the newborn. In spite of this, anti-D
      antibodies having relevance to pregnancy are later detected in 1.8% of RhD
      negative mothers. Half of these cases could be prevented by routine anti-D
      prophylaxis given to the mothers during weeks 28 to 34 of pregnancy. Convincing
      evidence of the effectiveness of this measure has accumulated in the last few
      years, and application of the treatment is justified also in Finland.

PMID- 22372072
TI  - [Update on current care guidelines: diabetes].
AB  - About 500,000 people suffer from diabetes in Finland, a number which is predicted
      to double within the next 10-15 years. At the moment, diabetes can neither be
      prevented nor cured. Diabetes is associated with macrovascular complications
      (coronary heart disease, stroke) and microvascular disorders (kidney, eye and
      peripheral nerves). These complications affect the quality of life of patients
      and account for a substantial proportion of healthcare costs in Finland. The
      current guidelines offer recommendations for the diagnosis, screening, prevention
      and treatment of diabetes and its complications.

PMID- 22372073
TI  - [Unilateral nasal symptoms].
AB  - The most frequently appearing unilateral nasal symptoms or signs are stuffiness,
      rhinitis and bleeding. The etiology of unilateral symptoms must always be
      identified. Most commonly such symptoms are caused by structural, functional or
      inflammatory disorders. On the other hand, the cause may be a tumor, and
      appropriate further investigations are to be planned carefully. In addition to
      medical history and clinical examination, imaging of the nose and the paranasal
      sinuses, as well as biopsies taken from the nasal mucosa, are used to examine
      etiology for nasal symptoms and signs.

PMID- 22372074
TI  - [Surgery for lower nasolacrimal duct obstructions in adults].
AB  - Epiphora and purulent discharge are common and irritating clinical manifestations
      of nasolacrimal duct obstruction (NLDO). If conservative treatment fails,
      dacryocystorhinostomy (DCR) has proven an efficient surgical method. The aim of
      DCR is to bypass the obstruction by creating a stoma between the lacrimal sac and
      the nasal cavity. External DCR has been the gold standard for decades. In recent
      years with the development of nasal endoscopes, less invasive surgical
      techniques, such as endonasal endoscopic DCR have become an increasingly popular
      procedure in the treatment of patients with NLDO. In such patients, the success
      rates for both external and endonasal DCR are about 90% and a successful
      procedure has a significant impact on the quality of life.

PMID- 22372075
TI  - [Emergency rhinology].
AB  - The nose counteracts chemical, biological and mechanical insults from the outside
      word. Mechanical injuries to the nose are usually managed within few days.
      Fracture of the nasal septum and possible hematoma should be managed within one
      day. Nasal or paranasal infection will in most cases heal by symptomatic
      treatment or antibiotic medication. Sometimes the condition gets rapidly
      complicated, resulting even in a life-threatening infection. Nose-bleeding
      originates in most cases from the frontal part of the nose, whereby treatment
      with silver nitrate is simple and effective. Gauze packing or anterior-posterior
      tamponade with a balloon serve as first aid for bleeding of the posterior part.

PMID- 22372076
TI  - [Nasal polyposis].
AB  - Nasal polyposis is an adult type mucosal inflammation of unknown etiology. Polyps
      are found in 4% of the Finns and in 17% of asthma patients. The first-line
      treatment is corticosteroid nasal spray and, if necessary, corticosteroid nasal
      drops or orally administered corticosteroids. Lavages with sodium chloride
      solution can be utilized as supportive therapy. A combination of antibiotics and
      corticosteroida is worthwhile in purulent rhinosinusitis. Surgery is
      contemplated, if conservative therapy is ineffective. In ASA-intolerant
      asthmatics nasal polyposis may be severe and recur in spite of drug and surgical
      therapy.

PMID- 22372077
TI  - [It's normal--structural and functional variations of nose and paranasal
      sinuses].
AB  - Many nasal symptoms can be caused by normal variation in nasal structure or
      functioning. External nasal deformity necessitates further examinations only when
      remarkable or causing nasal blockage. Septal deformities are often seen also in
      patients without any symptoms. The size of nasal turbinates and the number or
      size of paranasal sinuses may vary causing sometimes problems in the
      interpretation of radiological imaging. Abnormal radiological findings can be
      detected also in asymptomatic patients, most commonly mucosal thickening and
      cysts of paranasal sinuses. Meticulous clinical examination including
      decongestation of nasal mucosa is a key for sorting out meaningful connection
      between symptoms and findings.

PMID- 22372078
TI  - [Sinusitis or rhinosinusitis?].
AB  - Acute or chronic infections of nasal and paranasal sinuses are very common.
      Previously a clear-cut classification based on the anatomy of nasal and paranasal
      sinuses was used when referring to infection of this region. When symptoms of
      infection or inflammation were present only within the nasal cavity, the
      condition was called rhinitis. In case the patient presented with symptoms or
      findings within the paranasal sinuses, it was called sinusitis. Research data
      obtained during the last few decades have added the term rhinosinusitis to the
      applied terminology.

PMID- 22372079
TI  - Every nurse is a nurse economist.

PMID- 22372080
TI  - Advanced practice nurse outcomes 1990-2008: a systematic review.
AB  - Advanced practice registered nurses have assumed an increasing role as providers
      in the health care system, particularly for underserved populations. The aim of
      this systematic review was to answer the following question: Compared to other
      providers (physicians or teams without APRNs) are APRN patient outcomes of care
      similar? This systematic review of published literature between 1990 and 2008 on
      care provided by APRNs indicates patient outcomes of care provided by nurse
      practitioners and certified nurse midwives in collaboration with physicians are
      similar to and in some ways better than care provided by physicians alone for the
      populations and in the settings included. Use of clinical nurse specialists in
      acute care settings can reduce length of stay and cost of care for hospitalized
      patients. These results extend what is known about APRN outcomes from previous
      reviews by assessing all types of APRNs over a span of 18 years, using a
      systematic process with intentionally broad inclusion of outcomes, patient
      populations, and settings. The results indicate APRNs provide effective and high
      quality patient care, have an important role in improving the quality of patient
      care in the United States, and could help to address concerns about whether care
      provided by APRNs can safely augment the physician supply to support reform
      efforts aimed at expanding access to care.

PMID- 22372081
TI  - Impact of the economic downturn on nursing schools.
AB  - The challenges posed by the economic downturn on baccalaureate nursing schools in
      the southeast as it relates to their perceptions of changes in the number of
      applicants, acceptance rates, employer recruitment efforts, and student clinical
      and job placement were explored. Responses from deans and program directors
      indicated nursing schools are experiencing negative effects of the economic
      downturn in the form of graduates having difficulty finding employment, decreased
      recruitment efforts from prospective employers, difficulty locating clinical
      placements for students, and no change in faculty applicants despite an increase
      in undergraduate student applicants as well as graduate student applicants. These
      multiple factors combined could signal the death knell for programs that are ill
      prepared to deal with such a crisis. Programs need to be aggressive in their
      efforts to draw health care recruiters as well as qualified faculty applicants to
      their campuses. Nursing schools must be able to clearly show why their graduates
      are superior to other programs' graduates when competing for both highly
      qualified faculty applicants and prospective student employers.

PMID- 22372082
TI  - Working with nurse educators' collective wisdom: implications for recruitment and
      retention.
AB  - Very few studies have been undertaken to consider the impact of nurse education
      environments on faculty retention and recruitment at a time when numbers of
      nursing faculty are falling to significantly low levels. The purpose of this
      article is to deconstruct nurse educators' experience, illuminate what nurse
      educators think is important to a quality work environment, and offer some
      critical questions that lead to the potential for change. The findings of this
      study suggest recruitment and retention of nurse educators are best addressed by
      a critical reexamination of organizations. Paying attention to what nurse
      educators believe is a quality work environment is a starting point for the
      process of deconstruction and reconstruction. This study contains compelling
      information that speaks to nurse educators' experience in what they believe is
      important in their workplace.

PMID- 22372083
TI  - Design, implementation, and evaluation of population-specific telehealth nursing
      services.
AB  - An implementation project was conducted to introduce a structure for telehealth
      nursing practice (TNP) which would address the specific needs of complex
      endocrinology patients in a hospital-based clinic. Outcomes of the pilot study
      include analysis of 727 advice calls, survey responses from a sample of 101
      patients, and feedback from 9 providers. Results support current evidence that
      disease management needs of chronically ill patients include prescription
      refills, medication and symptom management, lab results, and patient education.
      81.2% of patients rated satisfaction with telehealth nursing services as very
      high or high. A statistically significant relationship was found between
      timeliness of response and patient satisfaction. A focus on care coordination
      provided through telehealth nursing services may emerge as an important element
      in the care of chronically ill patient populations.

PMID- 22372084
TI  - What every nurse executive should know about staffing and scheduling technology
      initiatives.
AB  - Staffing in hospitals has a history of being based in opinion and tradition, not
      evidence. In recent years, for many, staffing practices have spun out of control
      creating chaos in overtime, the use of incentives, entitlement behaviors,
      dissatisfaction and frustration among nurses, and has opened doors for such
      things as staffing ratio legislation. Unprecedented pressures around budgets and
      financial performance have no doubt compounded this situation. We are in a new
      day, where technology can help us more than ever in a move towards staffing
      excellence and staffing practices based on evidence. Highly successful
      implementations of new technologies are the result of good leadership. The
      effectiveness of staffing and scheduling has significant business, safety, and
      quality implications that sit at the heart of the nurse executive's role.

PMID- 22372085
TI  - Demonstrating the value of the nursing workforce: an interview with Kathleen M
      White. Interview by Deborah Gardner.

PMID- 22372086
TI  - The effectiveness of reminder phone calls on reducing no-show rates in ambulatory
      care.
AB  - The objective of this study was to determine the effectiveness of daily reminder
      phone calls on reducing no-show rates in the ambulatory care setting. With the
      initiation of reminder telephone calls over a 6-month period, the no-show rate
      dropped by 50% from 8% to 4%. The no-show rate with reminder letters over 3
      months was reduced by 29% from 8.5% to 6%. Reminding patients by telephone call 1
      day prior to their appointment significantly increased the number of patients who
      arrived. Reminder phone calls also allowed patients to cancel their appointments
      if they weren't able to attend, rather than not showing up. Patients were given
      the option of rescheduling their appointments while on the phone at that time or
      calling back to reschedule. Most patients took the opportunity to reschedule at
      that time.

PMID- 22372087
TI  - Health reform in Massachusetts and the United States: an interview with Jonathan
      Gruber. Interview by Joanne Spetz and Christine T Kovner.

PMID- 22372088
TI  - The future of nursing and health IT: the quality elixir.

PMID- 22372089
TI  - Direct decision making vs. oblique decision making: which is right?
AB  - The complexity of health care environments is far too complicated for solutions
      to be developed by a small group or isolated upper managers. This direct
      leadership approach often fails. Leaders who use a more oblique approach focusing
      on areas such as long-term economic value, creating significant benefits for the
      wider community, and building robust social capital within the company are
      successful. Obliquity leadership is very appropriate for health care because of
      its constantly changing environment. Obliquity leadership and shared governance
      are great partners in reaching higher levels of involvement and high performance.

PMID- 22372090
TI  - 14-item resilience scale (RS-14): psychometric properties of the Brazilian
      version.
AB  - The Resilience Scale (RS) was developed to evaluate the levels of resilience in
      the general population. Its reduced version (RS-14) has presented reliable
      internal consistency and external validity. However, its psychometric properties
      have not been systematically evaluated. The objective of this study was to
      present the psychometric properties of the Brazilian RS-14. A total of 1,139
      subjects selected by convenience (62.9% women) from 14 to 59 years old (M = 26.1,
      SD = 11.61) participated in the study. Exploratory factor analyses (EFAs) and
      parallel analysis were conducted in order to assess the factor structure of the
      scale. A 13-item single-factor solution was achieved. Confirmatory factor
      analyses (CFA) and multigroup CFA (MGCFA) corroborated the goodness of fit and
      measurement invariance of the obtained exploratory solution. The levels of
      resilience correlated negatively with depression and positively with meaning in
      life and self-efficacy.

PMID- 22372091
TI  - Psychometric evaluation of the appraisal of health scale in stroke survivors.
AB  - BACKGROUND/PURPOSE: Little is known about the cognitive appraisal process
      influencing poststroke depressive symptoms. Based on a framework derived from
      Lazarus and Folkman (1984), psychometric properties of the Appraisal of Health
      Scale (AHS) were tested. METHODS: Secondary analysis of data from 394 stroke
      survivors tested internal consistency reliability and construct validity of the
      AHS, consisting of 3 subscales (threat, benign, benefit). RESULTS: Cronbach's
      alphas were satisfactory (threat .92, benign .85, benefit .73). After principal
      axis factoring, two factors emerged (threat, benefit). Sequential multiple
      regression accounted for 43% of the variance in depressive symptoms (p < .001),
      partly explained by the threat and benefit subscales after controlling for
      depression history, disability, age, social support, self-esteem, and optimism.
      CONCLUSION: Threat and benefit AHS subscales demonstrated satisfactory evidence
      of internal consistency reliability and construct validity in stroke survivors.

PMID- 22372092
TI  - The MCSS-26: revision of the Manchester Clinical Supervision Scale using the
      Rasch Measurement Model.
AB  - BACKGROUND: Previously published accounts of the evaluation of the effects of
      clinical supervision, a structured system to support health service staff, have
      been mainly contained to small scale qualitative studies. Over the past decade,
      the 36-item Manchester Clinical Supervision Scale (MCSS) has transformed the
      evaluation landscape and has been used as a quantitative outcome measure in
      upward of 90 licensed studies in 12 countries worldwide. The factor structure has
      been replicated by other researchers and the psychometric properties have been
      found robust. However, it had not been previously tested empirically using newly
      available and sophisticated statistical analyses. PURPOSE: This study tested the
      original factor structure and response format of the MCSS for goodness of fit to
      the Rasch model, using Rasch Unidimensional Measurement Model (RUMM) 2030
      software, and investigated the validity of the questionnaire for both nursing and
      allied health (AH) staff. METHODS: A series of Rasch analyses were conducted on
      the seven subscales of the MCSS. The default procedure for RUMM software uses the
      partial credit model, which allows items to have varying numbers of response
      categories and does not assume the distance between response thresholds is
      uniform. RESULTS: Detailed Rasch analyses indicated that the 36-item version of
      the MCSS could be reduced to 26 items and result in improved fit statistics for
      six subscales rather than seven. CONCLUSIONS: This study reconfirmed the
      established psychometric properties of the MCSS, now renamed the MCSS-26.

PMID- 22372093
TI  - Translation and validation of the Korean version of Family Scale.
AB  - BACKGROUND: Familism is an important and complex clinical issue because of its
      significant impact on family caregiving of elders. PURPOSE: The purpose of this
      study was to examine the psychometric properties of a Korean-translated version
      of the Family Scale (FS-K) among Korean adults. A descriptive, cross-sectional
      survey design was used. METHODS: A panel of experts completed the initial
      translation into Korean and back-translated the FS. Upon establishment of the
      content and translation equivalence between English and Korean versions of the
      FS, psychometric properties were evaluated for reliability and construct validity
      with a sample of 577 adults. RESULTS: The internal consistency of FS-K was found
      to be acceptable, and Cronbach's alpha coefficient was .75. For construct
      validity, the mean scores of the FS-K were significantly different for gender and
      marital status (p < .05). For the FS-K, six components were extracted, accounting
      for 53.9% of the variance. CONCLUSIONS: Results of this study suggest that the FS
      K can be used as a reliable and valid measure of familism among Korean adults.
      The FS-K will contribute to the understanding of familism for family caregivers
      caring for elders in both research and clinical practices.

PMID- 22372094
TI  - Made in the U.S.A.? No thanks!

PMID- 22372095
TI  - Bed sharing and SIDS: understanding the risks.

PMID- 22372096
TI  - In your pocket.

PMID- 22372097
TI  - Blogging the nursing life.

PMID- 22372098
TI  - Introducing handheld computers into home care.
AB  - In the fall of 2009, Bayshore Home Health (BHH) provided tablet computers to 75
      home care nurses working in Barrie, Ont. The devices were equipped with an
      embedded evidence-based documentation system and loaded with decision-making
      supports such as drug reference databases. The technology was designed to
      facilitate client assessment, care planning and evaluation at the point of care.
      This article documents the experience of implementing handheld computers in a
      home care setting and presents the lessons learned from the perspectives of the
      BHH executive team and front-line nurses. These groups were asked to complete
      online surveys, developed by the BHH research and evaluation steering committee,
      to assess the impact of the implementation on the organization, its nurses and
      its clients. An analysis of the feedback indicated support for the
      implementation. However, both groups had concerns about the capability of the
      hardware and software to meet the needs of decentralized home care nurses working
      in both urban and rural areas. Front-line nurses also identified the impact of
      handheld computers on the time required for charting and on the nurse-client
      relationship as areas of concern.

PMID- 22372099
TI  - Life's turning points shape a career--or two.

PMID- 22372100
TI  - Broadband access equals better connections.

PMID- 22372102
TI  - [A large gap in the nursing profession].

PMID- 22372101
TI  - Saturated fat and CVD: the role of milk products in reducing risk.

PMID- 22372103
TI  - [Promoting an absolute culture of patient safety].

PMID- 22372104
TI  - [The blood transfusion, a story of donations].
AB  - An anonymous and voluntary gesture, which is precious, even vital for the
      recipient whose health is seriously under threat, blood donation is an act of
      solidarity between humans. A gift of this precious, vital liquid--blood--to
      another self. Sustained by a powerful research dynamic, blood transfusion is a
      relatively recent practice which is based on a complex compatibility system.

PMID- 22372105
TI  - [Ensuring the safety of donated blood].
AB  - Blood donation is the only way of collecting the main components namely red blood
      cells, platelets and plasma. While chemical treatments and analyses help to
      control transfusion contamination risks, the best precaution remains the respect
      of very strict regulations by the donor.

PMID- 22372106
TI  - [Blood transfusions, a closely monitored procedure].
AB  - A blood transfusion is a medical procedure which, in most cases, is delegated to
      a nurse. Strictly regulated, it requires vigilance at every stage. In the
      transfusion safety chain, the nurse plays a central role, notably in terms of
      information, identification, control, traceability, monitoring and reporting.

PMID- 22372107
TI  - [The nurse, a key player in transfusion safety].
AB  - In the chain of transfusion safety, the nurse is the last line of defence in the
      battery of controls to avoid transfusion errors. The final pre-transfusion test
      carried out at the patient's bedside is a meticulous procedure. It involves cross
      referencing documents, checking the identity of the patient and determining the
      ABO blood group through an agglutination test.

PMID- 22372108
TI  - [A choice of the heart, pediatric cardiac nursing].

PMID- 22372109
TI  - [When consciousness goes].
AB  - Some neurodegenerative diseases gradually affect the patient's consciousness.
      While the patient may be declared incompetent, decisions concerning treatment
      must take into account his or her wishes, however weakly they may be expressed. A
      real ethical challenge for all the caregivers who must ensure the person's
      dignity is maintained and refrain from demonstrating therapeutic obstinacy.

PMID- 22372110
TI  - [An area within the hospital to talk about pain].
AB  - 2011, at the request of the French department of health, was devoted to patients
      and their rights. Various initiatives have been implemented in healthcare
      institutions to promote the place of users in our healthcare system. In Clermont
      Ferrand, a new "pain health information area" has just been created.

PMID- 22372111
TI  - [Family issues after the birth of a child].
AB  - After the birth of a child, all members of the family are expected to adapt. This
      common nursing practice in Quebec provides considerable support for the parents.
      The maternity nurse, in order to establish the father's specific needs to help
      him adapt to being a parent, can, thanks to a short interview, define the
      strengths and resources offered by each member of the family.

PMID- 22372112
TI  - [A memory consultation clinic, an asset for Alzheimer's disease].
AB  - In the face of an ageing population and the significant prevalence of
      neurodegenerative diseases, a team of doctors from the Lamentin general hospital
      in Martinique has set up a memory clinic. Its objective is to reach out to and
      inform the public in order to encourage screening and early diagnosis. Treatment
      and support also form part of its missions.

PMID- 22372113
TI  - [The critical role of the nurse in successful non-invasive ventilation in acute
      respiratory failure].
AB  - Non-invasive ventilation is a common therapy for acute respiratory failure.
      Nurses play an important role in the setting up of this treatment, a time
      consuming process, as well as its monitoring. It has been shown that the
      tolerance of non-invasive ventilation significantly influences the success of
      this treatment.

PMID- 22372114
TI  - [A multi-professional educational approach for cardiac rehabilitation].
AB  - At Sud Echirolles general hospital, a multi-professional team from the cardiac
      rehabilitation departments joined forces in order to provide patients with high
      quality information. The objective is to help patients gain better knowledge of
      the pathology, to understand the medicines and treatments and to prevent risks
      linked to their return home, to stress or to noncompliance with treatments.

PMID- 22372115
TI  - A day at the outpatient clinic.

PMID- 22372116
TI  - [Nursing care of hyperkalemia].

PMID- 22372117
TI  - [The virtue of silence in nursing care].

PMID- 22372118
TI  - [The wonderful experience of a writing workshop].

PMID- 22372119
TI  - [PICC line].

PMID- 22372120
TI  - Big change in a small state will lead to massive opportunity.

PMID- 22372122
TI  - The fault lies not in the stars...

PMID- 22372121
TI  - Bath salts: an emerging danger.
AB  - We report a case of psychosis in an individual who has ingested a new compound
      known as "bath salts." Bath salts represent an emerging public health threat due
      to serious neuropsychiatric and behavioral symptoms associated with their use.

PMID- 22372123
TI  - Emory University School of Medicine.

PMID- 22372124
TI  - A changing environment brings new advocacy goals for MAG in 2012.

PMID- 22372125
TI  - Childhood obesity and child neglect.

PMID- 22372126
TI  - Quality of life of rural Georgia colorectal cancer survivors.

PMID- 22372127
TI  - Medicare and Medicaid audits on the rise.

PMID- 22372128
TI  - Final rule makes it easier and less risky for physicians that wish to participate
      in an ACO.

PMID- 22372130
TI  - Ditzels: a partial solution for the costs of medicine.

PMID- 22372129
TI  - Holiday + new hospital computer system = high-risk discharge.

PMID- 22372131
TI  - [The research of Valeriana amurensis seed germination characteristics].
AB  - OBJECTIVE: To study the effect of different treatments on the Valeriana amurensis
      seed germination rate. METHODS: Used different chemical reagents and seed
      soakings on the routine germination test and the orthogonal test of the Valeriana
      amurensis seed, calculated the germination rate under different germination
      condition. RESULTS: Valeriana amurensis treated with different chemical reagends
      had different germination rate. The suitable immersion time could enhance
      Valeriana amurensis seed germination rate. Different treatment time, different
      disposal temperature, different germination temperature would have an impact on
      the Valeriana amurensis seed germination rate. CONCLUSION: In order to raise the
      Valeriana amurensis seed germination rate, use appropriate treatment on the seed
      before plant seeds; The seed growing must under suitable time and temperature.

PMID- 22372132
TI  - [Establish efficiently transformation system of the Isatis indigotica].
AB  - OBJECTIVE: To build up a method of efficiently transforming Isatis indigotica
      with the Agrobacterium. METHODS: Two kinds of Agrobocterium: ATCC 15834 and
      RI1601 were used to treat different fraction of Isatis indigotica. Explored the
      effect of cocultured, different antibiotic concentration and the media on
      multiply the hairy roots. RESULTS: The explants with out coculture had had higher
      survival rate rooting rate and earlier sprout time. After ultrasonic treatment of
      plant, the indacement rate was two times than that of untreated one; The best
      antibiotic concentration was 400 mg/L; The proportion of the grow speed of the
      hairy root in the liquid culture media was 2 - 3 times than that of solid culture
      media, and 37 times of common roots. CONCLUSION: The method is useful for
      establishing an efficiently transformatiem system of Isatis indigotica by
      Agrobacterium.

PMID- 22372133
TI  - [The degradation on cultivated Gastrodia populations and prevention measures].
AB  - OBJECTIVE: To propose views and concepts on the degradation of cultivated
      Gastrodia populations. METHODS: The differences between natural and cultivated
      Gastrodia populations were compared and discussed in terms of their biological
      features, qualities and yields. RESULTS: There were changes and degradation in
      biological features and some important properties of yield in cultivated
      Gastrodia. CONCLUSION: The direct reason of cultivated Gastrodia degradation is
      the ecological disturbace of forests and the decreasing amount of natural
      Gastrodia populations; The indirect reason is manual pollination and other
      changes of the natural growing environment.

PMID- 22372134
TI  - [Study on fibrolytic and hypotensive activity of earthworm homogenate of
      ultrafiltration separation from enzymolysis].
AB  - OBJECTIVE: To study the fibrolytic and hypotensive activity of earthworm
      homogenate of ultrafiltration separation from simulated enzymolysis of
      gastrointestinal tract system. METHODS: The before and after enzymolysis
      homogenate of fresh earthworm was seperated with different pore size PVDF
      ultrafiltration membrane and its fibrolytic and hypotensive activity was assayed.
      RESULTS: The fibrolytic activity of the total homogenate after enzymolysis
      overall changed little, but decreased in the the site of higher molecular weight
      and increased in the lower site of molecular weight; The ACE inhibitory activity
      improved, especially in the filtrate of the MW 4000 membrane. CONCLUSION: The
      fibrolytic activity of earthworm homogenate was not reduced by the digestive
      simulated enzymolysis, and the retention site of MW 10 000 membrane have more
      fibrolytic activity; The hypotensive activity of earthworm homogenate is enhanced
      by the digestive simulated enzymolysis. So the stronger activity could be
      obtained from enzymolysis.

PMID- 22372135
TI  - Prokaryotic expression of CP gene of Fritillary virus Y infecting Thunberg
      fritillary and antiserum preparation.
AB  - OBJECTIVE: To prepare antiserum against Fritillary virus Y (FVY) CP for detecting
      FVY and study serological relationships with other viruses. METHODS: Specific
      primer was designed according to Genbank (accession: AM039800) to amplify CP gene
      of FVY infecting Thunberg fritillary. Sequence relationship with other
      potyviruses was made by Blast. The CP gene was inserted into pSBET and expressed
      in Escherichia coli BL21 (DE3) plys E strain. The object protein was purified by
      12% SDS-PAGE firstly and subsequently 5% - 20% gradient SDS-PAGE. The antiserum
      against the CP was raised in mouse and its specificity was confirmed by Western
      blot analysis. The reactivity of the antiserum produced to FVY CP was tested by
      Western blot against the over-expressed coat proteins of 17 potyviruses. The
      ability to combine with nature FVY particles was confirmed by ELISA analysis.
      RESULTS: It shared 81.2% nucleotide acids identities with TrVY (Tricyrtis virus
      Y, AY 864850) CP gene, 68.1% with SMV-P (Soybean mosaic virus Pinellia strain,
      AJ507388. 2) CP gene and 67.2% with ZYMV (Zucchini yellow mosaic virus Luan
      isolate) CP gene. The prepared antiserum was special to FVY CP, also reacted
      moderately to the expressed CP of SMV-P (Soybean mosaic virus Pinellia strain)
      and weakly to that of ZYMV (Zucchini yellow mosaic virus Luan isolate).
      CONCLUSION: The antibody could combine to nature FVY particles and the antiserum
      is suitable for FVY detection by ELISA in large scale.

PMID- 22372136
TI  - [Study on the composition and pharmacological function change of rhizoma
      polygonati before and after processing].
AB  - OBJECTIVE: To discuss the processing mechanism of Rhizoma Polygonati (RP) through
      studying the correlation between the change of composition and pharmacological
      function in raw and processed RP. METHODS: The extraction of petroleum ether,
      methylene dichloride, ethyl acetate and 1-butanol of the raw and processed RP
      were compared by HPLC. The compounds changed in processed RP in the methylene
      dichloride extraction were further identified with reference substances. The
      immune function of methylene dichloride extraction of raw and processed RP were
      compared. RESULTS: The changed compound in concentration was determined to be 5
      Hydroxymethylfurfural. After processed, the concentration of 5
      Hydroxymethylfurfural sharply increased. The carbon clearance index (P < 0.01)
      and coefficient of phagocytosis (P < 0.05) were increased remarkably by processed
      RP comparing to those of the normal saline and raw RP. CONCLUSION: The increase
      of immune function of processed RP may be related to increasing of concentration
      of 5-Hydroxymethylfurfural. The results provide a better understanding of RP
      processing.

PMID- 22372137
TI  - [Analysis of rDNA-ITS sequences and similarity of radix paeoniae].
AB  - OBJECTIVE: To establish molecular authentication standards of Radix Paeoniae.
      METHODS: PCR method was used to determine rDNA-ITS sequences of sample S1 and
      sample S2 including ITS1, 5.8S, and ITS2. The sequences were analyzed by BLAST
      and DNAMAN software. rDNA-ITS sequences of Paeonia lactiflora Pall., Paeonia
      veitchii Lynch. and their counterfeit were analyzed by DNAMAN software. RESULTS:
      Established three molecular authentication standards on Radix Paeoniae: (1) The
      genera of samples was determined by the results of BLAST; (2) The species of
      samples were determined by the similarities; (3) The specific base positions
      confirmed the species of samples. Based on the sequence alignment and base
      differences, sample S1 was identified as Paeonia lactiflora Pall., and sample S2
      was identified as Paeonia veitchii Lynch. CONCLUSION: This paper can give an
      effective way of Radix Paeoniae identification. What's more, it gives a good
      example for other Chinese Medicinal Materia authentication.

PMID- 22372138
TI  - [Analyze on HPLC fingerprint of four main metropolis of herba pogostemonis].
AB  - OBJECTIVE: To establish a method for analyzing HPLC fingerprint of Herba
      pogostemonis and compare the variability of four main producing areas. METHODS:
      Diamonsil (R) C18 column was used, the Methanol-0.1% phosphoric acid (gradient
      elution) as a mobile phase and detection wavelength was set at 254nm, column
      temperature was 25 degrees C and flow rate was 1.0 ml/min. RESULTS: There were
      differences between the HPLC fingerprint of Herba pogostemonis from various
      places of production. The similarity of Herba Pogostemonis cultivated in tow
      regions of Zhaoqing Gaoyao and Guangzhou Huangcun was over 90%, and there were
      more differences among them with Zhanjiang Wuchuan and Hainan Wanning.
      CONCLUSION: The method is reliable and accurate. The method can be used for the
      identification of the crude drug and the evaluation of its quality.

PMID- 22372139
TI  - [Pharmacognostic identification of Calystegia soldanella].
AB  - OBJECTIVE: To identify Calystegia soldanella and provide foundation for its
      further study and application. METHODS: Scanning electron microscope (SEM),
      upright microscope and UV were applied in the research. RESULTS: Laticifers were
      observed in the cortex and phloem of root, sclerenchymatous cells were cyclized
      in the outer phloem of stem, the stomas present on both adaxial and abaxial
      epidermis, the stomatal type was paracytic. Observed by scanning electron
      microscope, stomas distributed on and sank into both adaxial and abaxial
      epidermis; The surface of guard cells were smooth, and subsidiary cells were
      smooth or veined, the veins were perpendicular to guard cells on adaxial
      epidermis, while the veins were irregular on subsidiary cells of abaxial
      epidermis. And the absorption peaks were significantly in UV scanning spectrum:
      the ethanol extract had an absorption peak at 324nm; While the chloroform
      extract's at 241nm, 296nm and 316nm. CONCLUSION: Bases on the characteristic
      identification, micro-identification and physicochemical identification, SEM is
      further used in the identification of micro-morphological characteristics of
      Calystegia soldanella, and it will raise the accuracy of the identification of
      Calystegia soldanella.

PMID- 22372140
TI  - [Study on the flavanone constitutes of Buddleja davidii].
AB  - OBJECTIVE: To study the chemical constitutes of Buddleja davidii. METHODS: The
      constitutes were isolated and purified by silica gel column chromatography,
      polyamide column chromatography and macroporous absorption resin and their
      structures were elucidated by spectroscopic analysis. RESULTS: Seven compounds
      including Apigenin (1), Apigenin-7-O-beta-D-glucoside (2), Acacetin (3), Acacetin
      7-O-beta-D-glucoside(4), Acacetin-7-O-alpha-L-rhamnopyranosyl-(1-6)-beta-D
      glucopyranoside (5), Luteolin (6), Luteolin-7-O-beta-D-glueoside (7). CONCLUSION:
      All these compounds are obtained from this plant for the first time.

PMID- 22372141
TI  - [Study on chemical constituents of the root of Liriope platyphylla].
AB  - OBJECTIVE: To study the constituents from the root of Liriope platypgylla.
      METHODS: Six chemical constituents were isolated from the chloroform fraction and
      n-BuOH fraction from EtOH extract of Liriope platyphylla. RESULTS: Their
      structures were elucidated as beta-sitosterol-3-O-beta-D-glucopyranosile(I),
      palmic acid (II), ruscogenin (III), LP-C(IV), LP-D(V), 25 (S) -ruscogenin 1-O
      beta-D-xylopyranoside-3-O-alpha-L-rhamnopyranoside (VI), respectively.
      CONCLUSION: All these compounds are isolated from this plant for the first time.

PMID- 22372142
TI  - [Study on the triterpenoids from the fruits of Ligustrum lucidum].
AB  - OBJECTIVE: To study the triterpenoids from the fruits of Ligustrum lucidum.
      METHODS: The constituents were extracted with 95% EtOH, partitioned with
      different solvents, isolated and purified by silica gel, Sephadex LH-20 and PHPLC
      column chromatography. The structures were elucidated by physicochemical
      properties and spectroscopic data. RESULTS: Thirteen compounds were isolated and
      identified as methyl oleanolate (1), 3-O-acetylursolic acid (2), 3-ketooleanolic
      acid (3), 19alpha-hydroxyl ursolic acid (4), lupeol (5), 3-O-acetyl oleanolic
      acid (6), oleanolic acid (7), betulin (8), ursolic acid (9), fouquierol (10),
      19alpha-hydroxyl acetylursolic acid (11), 3-O-cis-P-coumaroyl maslinic acid (12)
      and 3-O-trans-P-coumaroyl maslinic acid (13). CONCLUSION: Compounds 1 - 4 are
      obtained from this plant for the first time.

PMID- 22372143
TI  - [Extraction and analysis of chemical components of essential oil in Thymus
      vulgaris of tissue culture].
AB  - OBJECTIVE: To extract the essential oils from the Seedlings, the Aseptic
      Seedlings and the Tissue Culture Seedlings of Thymus vulgaris and analyze their
      chemical components and the relative contents. METHODS: The essential oils were
      extracted by steam distillation, the chemical components and the relative
      contents were identified and analyzed by gas chromatography-mass spectrometry
      (GC/MS) and peak area normalization method. RESULTS: The main chemical components
      of essential oil in these three samples had no significant difference, they all
      contained the main components of essential oil in Thymus vulgaris: Thymol,
      Carvacrol, o-Cymene, gamma-Terpinene, Caryophyllene et al. and only had a slight
      difference in the relative content. CONCLUSION: This study provides important
      theoretical foundation and data reference for further study on production of
      essential oil in thyme by tissue culture technology.

PMID- 22372144
TI  - [Analysis of fatty acids in leaves of Loropetalum chinense and L. chinense var.
      rubrum by GC-MS].
AB  - OBJECTIVE: To extract and analyze fatty acids in leaves of L. chinense Oliver and
      L. chinense var. rubrum Yieh. METHODS: The fatty acids were extracted with
      Soxhlet extractor and identified by the GC-MS method. RESULTS: 31, 26 and 30
      components were identified from the leaves of L. chinense, the green leaves and
      red leaves of L. chinense var. rubrum. There were 19, 14 and 16 kinds of fatty
      acid in the respective leaves, which accounted for 99.09%, 95.31% and 98.83% of
      the total extraction, respectively. The main components in the extraction were
      oleic acid (30.77%, 47.01%, 75.28%), linoleic acid (48.49%, 29.26%, 0%),
      hexadecanoic acid (9.83%, 8.87%, 11.71%), octadecanoic acid (3.86%, 3.18%, 4.88%)
      and docosanoic acid (2.37%, 2.17%, 2.58%). CONCLUSION: Many kinds of unsaturated
      fatty acids exist in leaves of L. chinense Oliver and L. chinense var. rubrum
      Yieh. The leaves of these two plants can be used as the traditional Chinese
      medicine.

PMID- 22372145
TI  - [Research on chemical constituents of xuefu zhuyu decoction].
AB  - OBJECTIVE: To investigate the chemical constituents of Xufu Zhuyu decoction.
      METHODS: Silica gel column chromatography, Sephadex LH-20 chromatography and
      crystallization were employed for the isolation and purification. The structures
      were elucidated by physicochemical properties and spectral analysis. RESULTS:
      Eleven compounds were isolated and identified as follows: palmitic acid (1),
      stearic acid (2), beta-sitosterol (3), oleanolic acid (4), pregnenolone (5),
      tangeratin (6), 4-hydroxy-3-butylphthalide (7), sorhamnetin (8), friedelinol (9),
      beta-ecdysone (10), ferulic acid (11). CONCLUSION: All these compounds are
      isolated from Xuefu Zhuyu decoction for the first time.

PMID- 22372146
TI  - [Effects and mechanism of drug serum of prepared radix polygoni multiflori on rat
      osteoblast in vitro].
AB  - OBJECTIVE: To study the effect of drug serum of prepared Radix Polygoni
      Multiflori on rat osteoblast (Ob) and its mechanism. METHODS: The animal serum
      was prepared by serum pharmacology means. The cells were getting by separating
      and inducing the SD neonatal rat skull bone. The proliferation and
      differentiation of Ob were detected by CCK-8, alkaline phosphatase (ALP) activity
      analysis. And RT-PCR method was used to determine the osteogenesis-related genes
      expression. RESULTS: Compared with control group, the groups with drug serum of
      prepared Radix Polygoni Mutiflori, 10%, 20% and 30% had an effect on promotion
      the proliferation significantly on Ob (P < 0.01). There was no concentration
      related manner among groups. The 5% and 10% drug serum decreased ALP activity at
      the post-translation phase compared with control group, but higher doses (20% and
      30%) did not have the same effect. However, drug serum of PR/MIN increased
      significantly osteogenesis-related genes (OC, ALP, Cbfalpha1) mRNA expression (P
      < 0.05). CONCLUSION: The drug serum of prepared Radix Polygoni Multiflori can
      stimulate osteoblast proliferation in vitro, and its mechanism may be associated
      with increasing osteogenesis-related genes expression.

PMID- 22372147
TI  - [Effects of Na-FA on gastrointestinal movement and gastric ulcer in mice].
AB  - OBJECTIVE: To research the effects of Na-FA on gastrointestinal movement and
      gastriculcer in mice. METHODS: Using charcoal powder as an indicator, the effects
      of FA-Na on bowel movement of mice was evaluated by determining the propulsive
      percent-age of charcoal powder in normal mice, inhibition of small intestinal
      propulsion model induced by Compound Diphenoxylate and spleen asthenia and
      diarrhea model caused by Rheum officinale Baill; The acute gastric ulcer model
      was induced by intragastric alcohol given orally, the protective effect of FA-Na
      given ahead on gastric injury was evaluated, the ulcer index and the inhibition
      ratio of ulcer was calculated. RESULTS: FA-Na (intragastric administration) had
      inhibit effect on normal mice and diarrhea model caused by Rheum officinale,
      significantly synergetic effect on gastrointestinal asynersis induced by Compound
      Diphenoxylate, and protective effect on mice gastric mucosal injury cause by
      dehydrated alcohol. Compared with the positive control drug Ranitidine, the ulcer
      index and ulcer inhibition ratio large doses of FA-Na had no significant
      difference. CONCLUSION: The acute toxicity of FA-Na is very low, it has the
      effects of antidiarrheal and anti-gastric ulcer.

PMID- 22372148
TI  - [Analyze and compare activities of polysaccharide form rhizoma chuanxiong and
      radix paeoniae rubra].
AB  - OBJECTIVE: To explore the difference of biological activities between two Chinese
      Herbs polysaccharides. METHODS: Extracted two kinds of Chinese Herbs
      Polysaccharides by hot water, and determined the content of Polysaccharides.
      Determined the antibacterial activity with turbidimetry. Explored antioxidant
      activity using an in vitro antioxidant analysis, probed into the effects on cell
      growth with MTT colorimetric analysis. RESULTS: The two polysaccharides both
      showed activities on the antibacterial, anti-oxidation and promotion of cell
      growth but different in degree. The Radix Paeoniae Rubra polysaccharide was
      stronger than Rhizoma Chuanxiong in antioxidant and antimicrobial activities, and
      weaker in promotion of cell growth activity. CONCLUSION: Activity differences
      exist between the two polysaccharides and the activities show some complementary
      effects. The differences provide important value in research on polysaccharide
      compound.

PMID- 22372149
TI  - [Study on the inhibit mechanism primarily of extracts from Coptis on clinical
      resistant the medicine of Staphylococcus aureus].
AB  - OBJECTIVE: To discuss the inhibit mechanism primarily of extracts from Coptis on
      clinical resistant the medicine of Staphylococcus aureus. METHODS: Used SDS-PAGE
      electrophoresis, spectrophotometry and semiautomatic biochemistry analysis to
      detect the accumulated concentration of norfloxacin, membranin electrophoretogram
      and the enzymatic activity in extracellular fluid before and after Coptis extract
      disposition. RESULTS: The accumulated concentration of medicine norfloxacin
      within the experiment strains which treated with Coptis extract was clear higher
      than that of the blank space (P < 0.01); some proteins which molecular weights
      were in 35 - 38 kDa rebound expressed after Coptis extract treated; The
      extracellular fluid enzymic activities of resistant Staphylococcus aureus had no
      significant difference (P > 0.05). CONCLUSION: The inhibit mechanism primarily of
      extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus
      is the results of the combined action of various chemical composition and multi
      target interaction, and the exact molecular mechanism remains to be further
      researched.

PMID- 22372150
TI  - [Inhibitory effect of Astragalus polysaccharides on apoptosis of pancreatic beta
      cells mediated by Fas in diabetes mellitus rats].
AB  - OBJECTIVE: To observe the effects of Astragalus polysaccharides (APS) on the BG,
      insulin and C-peptide in serum, ultrastructure and Fas expression of pancreatic
      beta-cells in diabetes mellitus (DM) rats. METHODS: Thirty DM rats induced by
      streptozotocin (STZ) were randomly divided into three groups: DM group, APS 200
      mg/kg group, APS 400 mg/kg group, another 10 normal rats were taken as the
      control group. The drug was given by intraperitoneal for 6 weeks. The level of BG
      was determined by ONE TOUCH II machine. The levels of insulin and C-peptide in
      serum were measured by radioimmunoassay. The expression of Fas was observed by
      immunohistochemistry. Moreover, the TEM was used to observe the ultrastructure of
      pancreatic beta-cells. RESULTS: (1) DM rats showed significant increase in BG
      compared with control group (P < 0.05). APS could decrease the level of FG (P <
      0.05). (2) DM rats showed significant decrease in insulin and C-peptide in serum
      compared with control group (P < 0.05). APS has no appearance effects on the
      levels of them (P > 0.05). (3) The expression of Fas of beta-cells was
      significantly increased in DM rats, which was significantly inhibited by APS
      treatment. (4) It showed degenerative changes of pancreatic beta-cells
      ultramicroscopic structure of the DM rats, while APS treatment could
      significantly improve the damage. CONCLUSION: APS exerts its therapeutic effects
      on DM, which maybe related to the significant decreasing of the Fas expression
      and inhibiting the apoptosis of beta-cells.

PMID- 22372151
TI  - [Optimization of supercritical fluid extraction of ursolic acid from follum
      eriobotryae by response surface methodology].
AB  - OBJECTIVE: To optimize the conditions for extracting ursolic acid from Follum
      eriobotryae with supercritical fluid extration (SFE). METHODS: The contents of
      ursolic acid in the extracts were determined by HPLC. Based on single factor
      experiment and response surface methodology, a mathematical model for SFE of
      ursolic acid was built. RESULTS: The result showed that the optimum condition
      paremeters were as follows: temperature 61.6 degrees C, extraction pressure 25.8
      MPa, dynamic extraction time 40 min. Under these conditions, theoretical
      extraction rate of ursolic acid was 3.96 mg/g. CONCLUSION: The eptimal process is
      reliable.

PMID- 22372152
TI  - [Study on extraction process for the icariin of hugu capsule with ultrasonic
      technology].
AB  - OBJECTIVE: To study the best ultrasonic technology of the extraction of icariin
      of Hugu capsule. METHODS: Used the content of icariin as index, orthogonal
      experiment was carried out to investigate 4 influential factors as follows: the
      ultrasonic power (A), the ultrasonic frequency (B), the material fluid ratio (C),
      the time (D). RESULTS: The best extraction conditions were as follows: the
      ultrasonic power was 120 W, the ultrasonic frequency was 28 KHz, solid-liquid
      ratio of 1 : 35, the extraction time was 10 min. CONCLUSION: Optimization of
      extracting process is simple, quick and low energy consumption. Under these
      conditions, the extraction of icariin is 1.8 times higher than that of the
      traditional extraction method.

PMID- 22372153
TI  - [Extract berberine hydrochloride by aqueous two-phase system].
AB  - OBJECTIVE: To study the aqueous two-phase system which could be used for
      extraction of berberine hydrochloride. METHODS: Three aqueous two-phase systems
      were used for extraction experiment firstly, the best one was chosen from that,
      and then the single factor experiment and orthogonal experiment were carried out.
      RESULTS: 10 mL 95% ethanol with 10 mL 2.2 mol/L ammonium sulfate could make a
      aqueous two-phase system, added 600 mg berberine hydrochloride whose purity was
      53.22% into it, regulated its pH to 4, then the system was put into water-bath
      heater (70 degrees C) for 30 min, the extraction rate could reach 99.29%;
      Collected the extraction liquid, dried it under 40 degrees C, the purity of
      berberine hydrochloride was 88.43%. CONCLUSION: This system is a suitable aqueous
      two-phase system for extraction of berberine hydrochloride.

PMID- 22372154
TI  - [Separation and purification process of total flavones from four-leaf diet
      decoction].
AB  - OBJECTIVE: To investigate purification process of total flavonoids from four-leaf
      diet decoction with macroreticular resin. METHODS: By using the static absorption
      tests and dynamic absorption tests with different types of macroreticular resins,
      the better parameters were found and the orthogonal design were used in purified
      craft. RESULTS: AB-8 resin showed the best absorption property with the following
      technological conditions: the ratio of resin (g) - extract (mL) is 1.2: 1, the
      ratio of column diameter to height was 1: 12, then washed with water to
      colorless, and the volume of 80% ethanol was 7 BV. CONCLUSION: The process is
      stable and the purity of total flavones is up to 85%.

PMID- 22372155
TI  - [Study on the preparation of curcumin inclusion complex and its stability].
AB  - OBJECTIVE: To prepare the curcumin inclusion complex and study its stability.
      METHODS: Beta-cyclodextrin (beta-CD) was chosen as inclusion material and
      orthogonal design method was used. UV-Vis spectrophotometer was used to determine
      the solubility and content of different samples. They were placed under
      conditions of light and the solution containing Fe(3+) to determine their
      stability. RESULTS: The optimum preparation procedure were : curcumin and beta
      cyclodextrin feed molar ratio of 1: 1, the concentration of ethanol was 40%, 40
      degrees C inclusion temperature and 1 h reaction time. CONCLUSION: Inclusion
      complex prepared under eptimal condition is stable.

PMID- 22372156
TI  - [Study on the quality standard of danmo capsule].
AB  - OBJECTIVE: To establish the quality standard for Danmo capsule. METHODS: TLC was
      used for the qualitative identification of Salviae Miltiorrhizae Radix Et Rhizoma
      and Lonicerae Japonicae Flos. HPLC was used to determine the content of
      Salvianolic acid B. RESULT: TLC spots were clear and well-separated without
      negative interference. The linear range of Salvianolic acid B was 0.120042 -
      2.40084 microg (r = 0.9999) with an average recovery of 103.63%, RSD was 0.6% (n
      = 6). CONCLUSION: The method is simple, accurate and reliable. It can be used for
      the quality control of Danmo capsule.

PMID- 22372157
TI  - [Exploring the potential molecular target proteins of yinchenhao decoction using
      computer systemic biology].
AB  - OBJECTIVE: To predict the potential molecular target proteins of Yinchenhao
      decocation by computer systems biology approaches. METHODS: For text mining,
      TCMGeneDIT was used to retrieve association information regarding genes or
      proteins, Artemisiae scopariae of 17 main compounds absorbed into blood after
      oral administration of Yinchenhao decoction, target identificetion and analysis
      was conducted to determine the target proteins of those compounds using
      PharmMapper sever. The proteins which had direct interaction with predictive
      target proteins were selected by screening BIND, BioGRID, DIP, HPRD, IntAct, MINT
      database. RESULTS: Four and eight proteins were found to respectively associate
      with Artemisiae scopariae herba and Rhei radix et rhizome. Six components
      including rhein, emodin, 6, 7-dimethoxy coumarin not only directly interacted
      with target proteins which were proved by experiments, but also interacted with
      other related proteins. Eight components such as isofradin-3-O-glycoside could
      only play assistant roles by interacting with related proteins. CONCLUSION: The
      result provides useful information for further research. It is expected it would
      be helpful for understanding the molecular mechanism of Yinchenhao decoction.
      Taken together, the protocol developed in the study may lead to a deeper
      understanding of a system as a whole in the mechanism of Chinses formula.

PMID- 22372158
TI  - T. asahii pulmonary infection as a complication of TNF-inhibitor and steroids:
      posaconazole pharmacotherapy and risk analysis.
AB  - We report the first documented Trichosporon asahii infection in a patient with
      connective tissue disease treated with a Tumor Necrosis Factor (TNF) inhibitor
      and describe an institutional root cause analysis for TNF inhibitor-associated
      infections. Fourteen patients with incident fungal infections during TNF
      inhibitor treatment were identified. They were matched with uncomplicated
      patients receiving TNF inhibitors or with rheumatoid arthritis (RA) patients
      managed without TNF inhibitors. We found that patients acquiring fungal
      infections were more likely to have graft versus host disease (GVHD) (p<0.05).
      Furthermore, infected patients were more likely (OR=24.4) to have multiple
      immunosuppressive therapies over the controls as well as several risk factors
      identified by the Infectious Disease Society ofAmerica (IDSA). The 3 patient
      deaths in our study were associated with GVHD and infliximab. Trichosporon was
      isolated in 1 patient receiving adalimumab. Our results suggest that these high
      risk patients be monitored closely for fungal infection.

PMID- 22372159
TI  - Top 10 facts you need to know about febrile seizures.

PMID- 22372160
TI  - The electronic age.

PMID- 22372161
TI  - A thousand cuts and a piece of cake.

PMID- 22372162
TI  - Syringocystadenoma papilliferum.

PMID- 22372163
TI  - Verruciform xanthoma: a special epidermal nevus.
AB  - Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD)
      syndrome is a rare X-linked hereditary disorder. Presentation varies from
      ichthyosiform nevus to complete limb amelia. We present a 17-year-old adolescent
      girl who presented with a 16-cm exophytic mass of the right foot that had been
      growing for 7 years as well as knee contracture. Deformed nails with
      onychorrhexis were noted bilaterally. History of multiple nonlinear erythematous
      skin lesions covered by dry waxy scales involving multiple body folds with sharp
      midline demarcation was obtained. The patient's family history was negative for
      consanguinity and similar conditions. Radiography showed right leg hypoplasia and
      osteopenia. These findings fulfill the diagnosis of CHILD syndrome.
      Microscopically, psoriasiform epidermal hyperplasia with marked orthohyper
      keratosis and neutrophilic exocytosis were noted. The papillary dermis was packed
      with foamy macrophages consistent with xanthomatous changes, namely verruciform
      xanthoma. Verruciform xanthoma, although rarely found in other conditions, is a
      characteristic finding.

PMID- 22372164
TI  - What is your diagnosis? Preauricular pit.

PMID- 22372165
TI  - Treatment of recalcitrant herpes simplex virus with topical imiquimod.
AB  - Herpes simplex virus (HSV) is a common, easily transmissible virus. There is
      growing awareness of acyclovir-resistant HSV particularly among immunocompromised
      patients, which may be due to protracted treatments with guanosine analogues.
      Given the considerable morbidity associated with other classes of antiherpetic
      medications such as foscarnet (renal impairment, seizures) and cidofovir (renal
      impairment, neutropenia), imiquimod, a toll-like receptor agonist that enhances
      the innate immunologic responses against the virus, has been utilized in treating
      acyclovir-resistant HSV. We present a case of a human immunodeficiency virus
      (HIV)-positive patient who was successfully treated with topical imiquimod after
      treatment failures with other oral antivirals.

PMID- 22372166
TI  - Painful annular pustular drug eruption induced by erlotinib in a patient with non
      small cell lung cancer.

PMID- 22372167
TI  - Secondary syphilis in an immunocompromised kidney transplant recipient.
AB  - As an increasing number of patients undergo successful solid organ
      transplantation, immunocompromised patients are encountered more commonly in the
      private practice office. Thus the evaluation of such patients should take into
      consideration the possibility of infection. We report the case of a kidney
      transplant recipient who took standard immunosuppressive therapy and presented
      with cutaneous findings of secondary syphilis. Skin biopsy and serologic testing
      confirmed the diagnosis. The patient was treated according to current guidelines
      from the Centers for Disease Control and Prevention. We present a brief review of
      the clinical presentation, pathologic findings, diagnostic methods, and treatment
      options for syphilis.

PMID- 22372168
TI  - Erythema ab igne: a case report and review of the literature.
AB  - Erythema ab igne (EAI) is a rare condition since the advent of central heating.
      Its incidence has been rising as heating sources are being used to treat chronic
      pain. Multiple activities that chronically expose patients to heating sources
      also have been documented with this condition. We present a case of EAI induced
      by the use of an electric blanket.

PMID- 22372169
TI  - Acremonium mycetoma: a case report and discussion.
AB  - Acremonium mycetoma is a rare fungal infection of the skin, tissue, and bones. We
      present a case of a 64-year-old man with mycetoma due to gardening. The clinical
      presentation, laboratory findings, and treatment options are reviewed.

PMID- 22372170
TI  - Merkel cell carcinoma: case report.
AB  - Merkel cell carcinoma (MCC), also termed cutaneous small cell carcinoma or
      trabecular carcinoma, is a rare tumor that most often presents as a solitary
      nodule on the head, neck, or extremities of older adults. It is an aggressive
      tumor that usually is fatal due to rapid metastasis. Involvement of lymph nodes
      at presentation can be used to predict survival. Because MCC is sensitive to
      radiation, it can be used as an adjunct to surgery. We report a case of MCC to
      alert clinicians of this potentially fatal tumor because early diagnosis and
      proper treatment may improve patient survival rates.

PMID- 22372171
TI  - Pretibial mucinosis in a patient without Graves disease.
AB  - Although an uncommon location, cutaneous mucinoses may present in the pretibial
      area in distinct clinical circumstances. The terms pretibial myxedema and
      pretibial mucinosis often are used interchangeably, but pretibial myxedema should
      be regarded as a type of pretibial mucinosis. We present a case of cutaneous
      mucinosis localized to the pretibial area of a patient without Graves disease.

PMID- 22372172
TI  - The diagnosis and management of pulmonary embolism.
AB  - Pulmonary embolism (PE), most commonly originating from thrombosis in the deep
      venous system of the lower extremities, remains a controversial area of medicine
      that frequently generates lively debate. Its clinical presentation varies from
      asymptomatic, incidentally detected pulmonary emboli to massive embolism
      resulting in sudden death. Despite the advances made in recent years, a number of
      fundamental questions remain unanswered regarding the pathogenesis, clinical
      presentation, diagnosis and treatment of this disease. The diagnosis of PE is
      confounded by a presentation that may be subtle, atypical, or obscured by a
      concomitant condition. Safe, minimally invasive techniques have been developed to
      improve the diagnostic accuracy of the clinical evaluation, and obviate the need
      to obtain pulmonary arteriography in all but a minority of patients. However, no
      single diagnostic test is sufficiently sensitive or specific for diagnosis in all
      patients. This dilemma has resulted in the development of numerous clinical
      scoring systems to stratify risk, pretest probability and help guide an
      appropriate diagnostic approach. Anticoagulation therapy with unfractionated
      heparin (UFH), low molecular weight heparin (LMWH), and Factor Xa inhibitors are
      the mainstay of therapy for acute PE. The choice of agent is influenced by
      disease severity, presence or absence of provokingfactors, patient comorbidities,
      and bleeding risk. These factors also determine whether measures such as
      thrombectomy, thrombolysis and vena cava filter placement may be employed as
      adjuncts to anticoagulation. Warfarin is the agent of choice for secondary
      prevention; newer agents such as direct thrombin and factor Xa inhibitors are
      emerging as safe and effective alternatives.

PMID- 22372173
TI  - An 18-year-old woman with Kabuki syndrome, immunoglobulin deficiency and
      granulomatous lymphocytic interstitial lung disease.
AB  - Granulomatous lymphocytic interstitial lung disease, or GLILD, is an uncommon
      condition associated with common variable immunodeficiency (CVID). We present an
      interesting case of an 18-year-old woman with Kabuki syndrome and CVID who was
      seen in our clinic for an abnormal chest CT scan. She was subsequently diagnosed
      with GLILD. There are no established guidelines for the treatment of GLILD in
      CVID. Immune globulin replacement therapy is the main treatment for CVID and
      higher doses of intravenous immunoglobulin (IVIG) may prevent the progression of
      chronic lung disease. Patients with CVID and GLILD are at increased risk for
      malignancy and their prognosis is worse compared to patients with CVID without
      GLILD.

PMID- 22372174
TI  - International efforts in plastic surgery: the Hartford Hospital, Connecticut
      Children's Medical Center and University of Connecticut experience in Ecuador.
AB  - Plastic and reconstructive surgery provide a necessary and essential service to
      public health efforts in resource-poor regions around the world. Disease
      processes amenable to plastic surgical treatment significantly contribute to
      worldwide disability, and it is the poor and underserved who are
      disproportionately affected. METHODS: We conducted a week-long plastic and
      reconstructive surgical trip to Latacunga, Ecuador to provide reconstructive
      surgical services for the underserved in this region. RESULTS: Over the course of
      a week, 97 patients received surgery. Most patients were young (mean age = 21.8
      years) and 50.5% were female. Burns and burn scar contractures were the most
      common diagnoses requiring surgery(21.6%), but cleft lip and palate deformities,
      scars, nevi, and congenital ear deformities comprised a significant proportion of
      the case load as well (17.5%, 11.3%, 12.4%, and 10.3%, respectively). There was
      one postoperative complication requiring reoperation. CONCLUSION: This short-term
      surgical trip successfully delivered essential reconstructive surgical care to an
      underserved population in rural Ecuador. Although this is most certainly only a
      fraction of the true surgical disease burden within this population, our
      experience provides a testament to the need for essential reconstructive surgical
      services in developing nations around the world.

PMID- 22372175
TI  - Cryptogenic organizing pneumonia with fatal respiratory failure.

PMID- 22372176
TI  - A novel device for minimally invasive harvest of the sural nerve.
AB  - The sural nerve is ideal for autologous nerve reconstruction. Traditional open
      harvest techniques result in a large prominent scar, delayed ambulation and poor
      patient satisfaction. Accordingly, we have designed a neurotome device to
      exclusively harvest the sural nerve as a safe and effective alternative to
      traditional techniques. Five patients underwent sural nerve harvest using our
      neurotome device. Scanning electron microscopy confirmed the preservation of
      histological nerve architecture when compared to nerves harvested by traditional
      open technique. Patients who underwent traditional open harvest of the sural
      nerve were asked to fill out a questionnaire to assess patient satisfaction.
      Ninety-three percent preferred a shorter scar, 20% complained of difficult
      ambulation, while 50% found troubling sensory deficits. Patients undergoing sural
      nerve harvest by our novel technique were satisfied with the cosmetic results and
      had less difficulty in ambulation. To optimize operative technique, cadaveric
      dissection of 15 limbs was done to further define the anatomic relationship of
      the sural nerve to the short saphenous vein. Minimally invasive harvest of sural
      nerve through our novel technique yields good cosmetic and functional results.

PMID- 22372177
TI  - Camurati-Engelmann disease--a rare cause of bone pain.
AB  - OBJECTIVE: Camurati-Engelmann disease or progressive diaphyseal dysplasia is a
      rare autosomal dominant disease characterized by cortical thickening of the long
      bone diaphyses accompanied by waddling gait, muscular weakness, hearing loss and
      chronic skeletal pain. We describe two cases of Camurati-Engelmann disease with
      differing presentations and review of the literature on several therapeutic
      options. METHODS: We present two cases of Camurati-Engelmann disease which
      responded to different medical therapies. Various diagnostic tests including
      radiographs, bone scan and genetic analysis are also described. RESULTS: These
      cases responded differently to the treatment options and provide an insight into
      the variable response of the disease. CONCLUSION: Diagnosis of this disorder is
      based on the clinical history, family history, clinical examination and imaging
      results. Recently genetic testing has become available for TGF-beta1 mutation
      Several therapeutic agents including biphosphonates, NSAIDs, prednisone and
      losartan have been described as therapeutic options with mixed results, as
      described in our cases.

PMID- 22372178
TI  - Upcoming oral factor Xa inhibitors for venous thromboembolism prophylaxis in
      patients undergoing major orthopedic surgery: rivaroxaban (Xarelto) and apixaban
      (Eliquis) review.

PMID- 22372179
TI  - Increasing Connecticut Medicine's involvement with the council, CSMS and county
      leadership.

PMID- 22372180
TI  - Report of the general manager. 1962.

PMID- 22372181
TI  - Resource utilization.

PMID- 22372182
TI  - Of the Dow and the Docs.

PMID- 22372183
TI  - The times they are A-changin'.

PMID- 22372184
TI  - Baby teething in early modern England: theory and therapeutic practice.
AB  - Oral and dental healthcare was a major medical concern in 16th- and 17th-century
      England. The analysis of a representative corpus from Early English Books Online
      (EEBO) reveals that the general principles and therapeutic management of baby
      teething were found most often in pediatric and midwifery treatises. The chapters
      devoted to this babyhood process usually gave information on factors determining
      teething onset, eruption schedule, order of appearance, associated disorders and
      short-term prognosis. Among the remedies available to alleviate children's pain,
      the authors mention anti-inflammatory herbal ointments, soothing fomentations,
      periodic mouthwashes, and minor surgery. Although the selected chapters on baby
      teething do not include detailed accounts of teething-related symptoms, one can
      find consistent data in the different descriptions and recipes provided. This
      scholarly agreement indicates systematic medical and midwifery practices to deal
      with a predictable, but frequently troublesome, stage of children's development.

PMID- 22372185
TI  - Diagnostic pulp testing in dentistry: how far have we come?
AB  - Techniques of pulp testing to determine vitality or sensibility have been in use
      for decades. While very little has changed in our methodologies, our
      understanding of the biology of the health and disease of the dental pulp has
      been enhanced. However, without thorough data collection using appropriate tests,
      and an integrated synthesis and analysis of this data, there is little chance of
      arriving at a diagnosis that will determine the proper course of treatment. While
      this need was clearly identified by Dr. Truman W Brophy over 130 years ago, we
      are still faced with these challenges today.

PMID- 22372186
TI  - Mozart: the toothache of a genius.
AB  - The medical history of Wolfgang Amadeus Mozart (1756-1791) has been pieced
      together from his letters and from anecdotes, but his dental health is one aspect
      which has been somewhat overlooked. It is known that, from an early age, he
      suffered from toothache and tooth abscesses, problems that may even have had
      other medical repercussions. In this paper, the authors explore and consider
      whether these negative experiences might have influenced Mozart's work and his
      attitude to teeth and dental pathologies. Two pieces of evidence from the life
      and work of this great composer provide clues: the aria entitled "A tooth decayed
      and sensitive to cold" (KV 209 a) (1772), containing the lament of a "sick man"
      suffering from toothache; and the first of the "Zoroastrian Riddles," which
      Mozart proposed during a masked ball in 1786, and whose solution is "teeth."
      Close examination of these two creative feats demonstrate that Mozart's attitude
      toward dental pathologies was calm and rational, so much so that he even managed
      to use the topic as a source of inspiration for a small jewel of a composition.

PMID- 22372187
TI  - The unicorn and the narwhal: a tale of the tooth.
AB  - From as far back as the early Roman era, detailed descriptions and artistic
      images of the unicorn have been imagined. In Europe, the Mediterranean and the
      Far East, this creature became accepted as real. Although such an animal had
      never actually been seen, it was said to have the appearance of a horse, the
      beard and cloven hooves of a goat, the tail of a lion, and a single, spear-like
      horn protruding from the center of its forehead. The unicorn myth originated
      shortly after unidentified horn-like objects, from six to ten feet long, began to
      appear in ancient European marketplaces. Physicians quickly ascribed outlandish
      healing properties to these horns, pulverizing them for the treatment of various
      diseases. In 1638, a Danish zoologist challenged these claims and provided
      evidence that the so-called "unicorn horn" was actually the tusk (tooth) of the
      narwhal from the Arctic seas. However, his findings remained unheeded for the
      next 100 years. This paper explains how the myth of the unicorn and the purported
      powers contained within the substance of its magical horn evolved from the ages
      old spoils of the Arctic fishing trade, where the narwhal was primarily speared
      for food and secondarily, for the export value of its ivory tusk. This unusually
      long, pointed and protruding single tooth, which breaks through the upper lip and
      the left jaw of each male narwhal, became a highly valuable commodity over the
      following centuries, due to its believed supernatural origins and curative
      qualities.

PMID- 22372188
TI  - The great revolution of the 20th century: antimicrobial agents.

PMID- 22372190
TI  - Joint Commission targets fatigue from clinicians' extended hours.

PMID- 22372189
TI  - Waldemar Wilhelm: father of oral and maxillofacial surgery in Colombia.
AB  - Waldemar Wilhelm (1913-1994) was honored by the Asociacion Colombiana de Cirugia
      Oral y Maxilofacial (Colombian Association of Oral and Maxillofacial Surgery) as
      the Father of Oral and Maxillofacial Surgery in Colombia. Born in Karlsruhe,
      Germany, Wilhelm graduated as a dentist from Johann Wolfgang Goethe University in
      1936. He emigrated shortly thereafter to Colombia, receiving his dental license
      there in 1943. He completed his oral and maxillofacial surgery training at
      Nordwestdeutsche Kieferklinic, under the tutelage of Prof. Dr. Dr. Karl
      Schuchardt in Hamburg. In 1950, he settled in Bogota, where he joined the
      Universidad Nacional School of Dentistry, opened Colombia's first oral and
      maxillofacial surgery department at Hospital San Jose, and trained the first
      maxillofacial surgeons in Colombia in 1958.

PMID- 22372191
TI  - What trends are driving hospital-MD alignment?

PMID- 22372192
TI  - Shared savings change dynamics between a hospital and surgeons.

PMID- 22372193
TI  - For implants, balancing choice and cost control.

PMID- 22372194
TI  - Shared savings don't jeopardize patient outcomes.

PMID- 22372195
TI  - Balancing staff productivity with open OR time.

PMID- 22372196
TI  - Overview: surgeon training and learning curve for performing robotic-assisted
      surgery.

PMID- 22372197
TI  - The ICD-10 shift: how the OR can aid in readiness.

PMID- 22372198
TI  - Lean: tackling waste in the sterile supply area.

PMID- 22372199
TI  - Is your ASC ready for closer scrutiny on sharps safety?

PMID- 22372200
TI  - Bone marrow disorders: recent advances, Part II. Introduction.

PMID- 22372202
TI  - Acute leukemias of ambiguous lineage.
AB  - The 2008 edition of the WHO Classification of Tumors of Haematopoietic and
      Lymphoid Tissues recognizes a special category called "leukemias of ambiguous
      lineage." The vast majority of these rare leukemias are classified as mixed
      phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and
      natural killer lymphoblastic leukemias are also included. The major
      immunophenotypic markers used by the WHO 2008 to determine the lineage for these
      proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive
      immunophenotyping is necessary to confirm that the cells indeed belong to 2
      different lineages or coexpress differentiation antigens of more than 1 lineage.
      Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22)
      Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome
      11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and
      B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to
      chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most
      from rapid allogeneic hematopoietic stem cell transplantation.

PMID- 22372201
TI  - Beyond the 2008 World Health Organization classification: the role of the
      hematopathology laboratory in the diagnosis and management of acute lymphoblastic
      leukemia.
AB  - The diagnosis of acute lymphoblastic leukemia (ALL) is made by evaluating
      morphology and immunophenotype. However, appropriate risk stratification and
      decisions regarding the intensity of therapy are influenced by additional
      clinical and laboratory testing that reflect the biology of the disease. Recent
      years have seen tremendous progress in uncovering genetic lesions that influence
      the biology of ALL. In recognition of these advances, the 2008 WHO classification
      incorporated the category of B-lymphoblastic leukemia/lymphoma with recurrent
      genetic abnormalities into the classification of precursor lymphoid neoplasms.
      Based on the knowledge available at the time, genetic lesions associated with
      distinct clinical features, immunophenotype, prognosis, or other unique
      biological characteristics were included in this category. Not surprisingly,
      significant novel genetic lesions that profoundly affect the biology of ALL have
      since been identified and will have a major impact on risk stratification and may
      ultimately be incorporated into future classification schemes. After establishing
      an initial diagnosis and treatment regimen, hematopathologists must also evaluate
      for minimal residual disease (MRD) to determine the need for additional
      intervention because MRD remains the most useful clinical indicator of disease
      progression and response to treatment. Doing so requires familiarity with not
      only morphology, but also flow cytometry and molecular genetics. Although not all
      of these applications are handled directly by the hematopathologist, it is our
      strong belief that meaningful involvement in patient care dictates that
      hematopathologists appreciate all aspects of ALL diagnosis and disease
      monitoring. This review covers the salient aspects of recent advances in the
      biology of ALL and evaluation of MRD, placing emphasis on how this information
      may ultimately be used to improve risk stratification and, as a result, patient
      outcomes.

PMID- 22372203
TI  - Mastocytosis and related disorders.
AB  - Mastocytosis represents a heterogeneous group of disorders characterized by an
      abnormal accumulation of mast cells in one or more organ systems. Mastocytosis is
      further divided into different subtypes according to the sites of involvement,
      laboratory findings, and degree of organ impairment. Cutaneous mastocytosis is
      diagnosed in the presence of skin involvement and absence of extracutaneous
      disease, and is most commonly seen in the pediatric population. Systemic
      mastocytosis, the disease form most commonly seen in adults, is characterized by
      the presence of multifocal, compact (dense) mast cell aggregates in the bone
      marrow or other extracutaneous organs. The mast cells may display atypical, often
      spindle-shape morphology and/or aberrant CD2 and/or CD25 expression. Elevation of
      serum tryptase and/or presence of KIT D816V mutation are other common findings.
      Systemic mastocytosis is further divided into different subtypes based on a
      combination of clinical features and laboratory findings. Recent studies have
      indicated that CD30 is frequently expressed in aggressive systemic mastocytosis
      and mast cell leukemia but infrequently in indolent systemic mastocytosis, and
      may be a useful marker for distinguishing these subtypes of systemic mastocytosis
      from one another. A group of related myeloid disorders, collectively termed
      myelomastocytic overlap syndromes, may pose diagnostic difficulty because of
      their significant clinical and pathologic overlap with systemic mastocytosis, and
      these will also be discussed in this review.

PMID- 22372204
TI  - Approach to peripheral blood film assessment for pathologists.
AB  - In today's age of advanced technology used in the diagnosis of many medical
      problems, the blood film stands out as an inexpensive and quick diagnostic tool
      that can generally be performed in most laboratories. Understanding when to
      perform a blood film and how it is made and having an organized sequential
      approach to reviewing the blood film are critical in the efficient use of this
      ubiquitous laboratory investigation. This article will review these issues, as
      well as common morphologic abnormalities found on blood films, and will discuss
      related clinical diagnoses that they represent. The final step of communicating
      the blood film findings in a clear and concise method to relay clinical
      suspicions to the end user will be discussed.

PMID- 22372205
TI  - Pathology of sickle cell disease.
AB  - Sickle cell disease (SCD) is a hereditary chronic hemolytic anemia with numerous
      clinical consequences. Intravascular sickling of red blood cells leads to
      multiorgan dysfunction. Although the pathophysiology of SCD has been well
      studied, there remains a lack of effective treatment. Refinements in overall care
      have improved quality of life; however, premature death is still not uncommon.
      SCD usually presents in childhood and is common in areas where malaria is (or
      was) common. The association with malaria is apparently of benefit to the
      individual because these individuals tend to contract a milder form of the
      disease. This review highlights the spectrum of pathology seen in people with
      SCD, with an emphasis on the pathogenesis of sudden death.

PMID- 22372206
TI  - Issues and critiques of the forthcoming risk evaluation and mitigation strategy
      (REMS) for opioids in pain management.
AB  - OBJECTIVE: To examine the history and suitability of the Food and Drug
      Administration's (FDA) Risk Evaluation and Mitigation Strategy (REMS) for
      reducing the safety risks associated with the use of opioid medications,
      including the risks of abuse and overdose. This article will highlight recent
      attempts by the FDA to introduce a class wide REMS for new and existing Schedule
      II long-acting opioid drugs. A critique of these current REMS efforts and
      recommendations for the future will also be provided. DESIGN: A literature review
      and commentary design are utilized to highlight issues surrounding REMS efforts
      and to explore possible future directions. Expert opinion is offered to
      potentially guide future efforts in this arena. CONCLUSIONS: The stated goal of
      the FDA's proposed class wide opioid REMS program is to decrease abuse, misuse,
      addiction and overdose deaths from opioid medications. While the REMS program may
      have theoretical capabilities for evaluating and addressing problematic drug use
      among prescribed patients, it is unlikely to reduce the bulk of prescription drug
      abuse that occurs with non-patients. Our recommendations provide some ideas on
      how the REMS program can be improved to achieve the goals set for it by Congress
      and the FDA.

PMID- 22372207
TI  - The Independent Medicare Advisory Committee: death panel or smart governing?
AB  - This comment explores whether health care reform legislation establishes an
      administrative body effectively charged with the rationing of health care
      resources; insofar as it establishes a presidentially appointed Independent
      Medicare Advisory Committee (IMAC). IMAC would be charged with "making two annual
      reports dictating updated rates for Medicare providers including physicians,
      hospitals, skilled nursing facilities, home health, and durable medical
      equipment." IMAC's recommendations would be implemented nationally, subject to a
      Congressional vote. Congress would be granted a thirty-day window to achieve a
      simple majority for or against the IMAC recommendations. Part I is an
      introduction. Part II of this article covers the history of American health care.
      It lays out the federal government's evolving role in the arena of public health
      and health care, starting in the mid-nineteenth century and continues up to the
      present day. Part III examines the existing process by which Medicare spending is
      controlled. This part focuses on the administrative procedures that control
      Medicare reimbursements. Part IV examines IMAC. This part discusses IMAC's
      statutory provisions and the administrative transparency laws IMAC would be bound
      to follow. The close of this part, draws on three analogies as a gauge for how
      IMAC will operate: Senator Tom Daschle's Federal Health Board (FHB) proposal; the
      administrative oversight of the Federal Reserve; and the United Kingdom's
      National Institute for Health and Clinical Excellence (NICE). Part V creates a
      snapshot of the U.S. health care system as it operates today. This part
      emphasizes cost, quality, and accessibility of health care, with comparisons to
      international and state-run health care systems. Throughout this article there
      are a number of words, phrases, and agencies that have been given acronyms. For
      convenience, an index of these acronyms is provided in an appendix following the
      article.

PMID- 22372208
TI  - Clinical medicine--what's it all about..?

PMID- 22372209
TI  - Consent and confidentiality in clinical genetic practice: guidance on genetic
      testing and sharing genetic information.

PMID- 22372210
TI  - Completion of the statement of fitness for work.

PMID- 22372211
TI  - Teaching medical professionalism.
AB  - Medical professionalism has been notoriously difficult to define and remains
      poorly understood. Because of this, graduates often have contrasting views on how
      it is best taught. These views should be considered and incorporated into
      teaching methods in order to enhance learning and development. Over a six-month
      consecutive period doctors and medical students in County Durham and Darlington
      Foundation Trust completed a questionnaire asking them to define professionalism,
      state where they felt they had learnt about professionalism and how important
      they feel professionalism is to them. They were also asked to identify how they
      felt teaching about professionalism was best delivered from a selection of
      educational resources. The findings highlight major differences between how the
      material is taught and how students and graduates feel they learn best about
      professionalism and more research into this field is needed.

PMID- 22372212
TI  - The role of the medical registrar.
AB  - The medical registrar in the acute on-call and out-of-hours setting is usually
      considered to be one of the busiest and most challenging jobs in the entire
      hospital. This is perhaps a reflection of the changes in the structure and
      organisation of acute medicine precipitated by the European Working Time
      Directive and Modernising Medical Careers. As well as the general feeling that
      medicine is being increasingly viewed as a default referral option by other
      specialties who are themselves becoming ever more sub-specialised. This article
      explores what the pragmatic role of the medical registrar broadly should be. The
      Medical Workforce Unit at the Royal College of Physicians is launching an
      initiative, part funded by the Department of Health, to answer this difficult
      question.

PMID- 22372213
TI  - Exploring variations in lung cancer care across the UK--the 'story so far' for
      the National Lung Cancer Audit.
AB  - The National Lung Cancer Audit was developed to improve the quality and outcomes
      of services for patients with lung cancer, knowing that outcomes vary widely
      across the UK and are poor compared to other western countries. After five years
      the audit is capturing approximately 100% of the expected number of incident
      cases across hospitals in England, Wales, Scotland, Northern Ireland and Jersey.
      Measures of process and outcome have improved over the audit period, such as the
      histological confirmation rate (64-76%), the proportion of patients discussed in
      a multidisciplinary team meeting (78-94%), and the proportion of patients having
      anti-cancer treatment (43-59%), surgical resection (9-14%) and small cell lung
      cancer chemotherapy (58-66%). These national averages hide wide variations
      between hospitals providing lung cancer care which cannot be accounted for by
      differences in casemix. This paper describes the evolution of the audit, and
      describes the ways in which it may have improved clinical practice.

PMID- 22372214
TI  - The white papers, quality indicators and clinical responsibility.
AB  - The coalition government has set out its stall in a cluster of white paper
      consultation documents. One theme to emerge is a commitment to monitoring
      outcomes. It is outcomes, underpinned by National Institute for Health and
      Clinical Excellence quality standards, that are to be used to regulate the NHS
      and these will be made available to the public. This paper sets out the
      importance of measuring quality in the NHS and some of the principles involved in
      analysis, presentation and interpretation of results. Clinicians have a duty to
      improve patient care and measurement and comparison is one of the tools at their
      disposal. Clinical involvement in the development of metrics and quality
      indicators is essential for meaningful results and it is vital that clinicians
      now take ownership of the quality of the clinical data captured on their
      patients.

PMID- 22372215
TI  - Hospital episode statistics: time for radical change.

PMID- 22372216
TI  - Risk management in the NHS: governance, finance and clinical risk.

PMID- 22372217
TI  - The need for a global alcohol strategy: 'upscaling the issue in a downstreaming
      environment'.

PMID- 22372218
TI  - Dementia for hospital physicians.
AB  - Many people with dementia are admitted to general hospitals, yet doctors feel ill
      prepared to manage them. Problems are often multiple and complex. In many cases,
      dementia is complicated by delirium. Medical assessment must be meticulous and
      requires collateral history taking, mental state examination and cognitive
      function testing. Hospital environments can be provocative, and the way staff
      interact with people with dementia can increase distress. Difficult behaviours
      usually represent unmet needs. The right approach by (all) staff can reduce this,
      including special efforts to establish reassuring, comforting relationships with
      patients. Try to see situations from the perspective of the person with dementia.
      Skilled communication is vital and family carers should be kept informed and
      involved. People with dementia are prone to side effects of prescribed drugs.
      Antipsychotic drugs are rarely the answer to difficult behaviours, but may be
      used in cases of psychosis or severe distress.

PMID- 22372219
TI  - Cavitating pulmonary tuberculosis: a global challenge.

PMID- 22372220
TI  - Opinions of general medical registrars on HIV teaching and their competence in
      HIV-related clinical issues.
AB  - More HIV-positive patients are living longer and presenting to non-infection
      specialties with non-HIV-related issues (eg diabetes, heart disease). National
      recommendations advise routinely offering HIV testing to all new registrants to
      primary care and all general medical admissions where community prevalence
      exceeds 2:1000. It is, therefore, imperative that all physicians are educated and
      competent in HIV infection, counselling and testing. This study aimed to
      establish regional medical registrars' opinions on teaching provision, and
      confidence in, HIV medicine. The results indicated a lack of confidence in HIV
      medicine and, in those without postgraduate rotations in HIV medicine or
      infectious diseases, a perception that HIV and infection-related teaching
      provision is inadequate.

PMID- 22372221
TI  - Why patients take part in the Royal College of Physicians Practical Assessment of
      Clinical Examination Skills (MRCP PACES).
AB  - The aim of this study was to examine patients' motivation to participate in the
      Royal College of Physicians Practical Assessment of Clinical Examination Skills
      (PACES). An exploratory cross-sectional study was performed with data collected
      via telephone interviews. All patients aged 18+ who participated in PACES at
      University Hospitals Coventry and Warwickshire in the last two years were invited
      to take part; 28 patients were interviewed. Data were analysed using thematic
      content analysis. Motivational factors identified included the opportunity to
      give something back for the care received, contributing to doctors' learning
      processes, altruism and being able to learn more about one's own condition.
      Patients believed that they offered real-life experiences that cannot be provided
      by actors. The social environment during PACES played a large part in volunteer
      retention. Recruitment of patient volunteers needs to emphasise the altruistic
      nature of the role in assisting the learning process for doctors and the
      subsequent benefit for future patients.

PMID- 22372222
TI  - Validation of a novel resin-porcine thorax model for chest drain insertion
      training.
AB  - Chest drain insertion in inexperienced hands carries a significant morbidity and
      mortality. The royal colleges, recognising this, stipulated that chest drain
      insertion be included as one of the core competences for all core medical
      trainees. However, there is no formal training in chest drain insertion included
      in training programmes. Simulation training should, in theory, provide a safe and
      objective method to overcome the obstacles in chest drain insertion training.
      There have been a number of attempts to find the ideal simulator for chest drain
      insertion with varying success. This article describes a model which is practical
      and affordable in all clinical skills labs, using porcine ribs mounted on a resin
      cast of a human thorax, and the data about the validation of the porcine-thorax
      model for chest drain insertion presented.

PMID- 22372223
TI  - Pyrexia and a rash.

PMID- 22372224
TI  - Analogies and metaphors in clinical medicine.
AB  - Medicine is traditionally known as an 'art', and not an exact 'science'. Medical
      images of clinical signs and pathology were communicated through 'metaphors' in
      the 19th and early 20th centuries to make recognition easier in anticipation of
      the clinical counterpart when encountered in medical practice. They have served
      as teaching aids, enhancing memory retention for medical students, nurses and
      doctors and have withstood the test of time. Standard medical textbooks contain
      metaphors that have become entrenched in teaching, learning and examining in
      medical schools and hospitals worldwide. The continued use of metaphors has given
      rise to an ongoing debate, particularly in Africa, due to the usage of
      inappropriate or unfamiliar metaphors which are not locally or culturally
      relevant. Despite this, medical analogies will no doubt continue to be useful for
      medical education, clinical practice and 'aide memoirs' for examinations, and
      bring light humour, for a long time to come.

PMID- 22372225
TI  - From the age of the pyramids to the superfast world--what has changed in the
      management of spinal injuries?

PMID- 22372226
TI  - Smoking status ascertainment and interventions in acute medical patients.
AB  - Hospital admission provides an opportunity to promote smoking cessation. Clinical
      guidelines recommend ascertainment of smoking status and delivery of cessation
      interventions in all consultations. In this article, smoking ascertainment and
      intervention among all patients admitted to medical wards in a UK hospital over a
      four-week period in 2010 were audited. Medical records of 767 patients were
      screened; 96 (13%) were current smokers, 243 (32%) ex-smokers and 233 (30%) non
      smokers. There was no record of smoking status in 243 (25%) individuals and this
      proportion varied between specialties. Of the 96 current smokers, only 23
      received documented cessation advice or pharmacological support. Four weeks after
      discharge, 31% reported that they were abstinent from smoking, representing 50%
      of those who received support and 20% of those who did not. Ascertainment of
      smoking status and delivery of cessation support to patients admitted to medical
      wards was low, suggesting that there is room for improvement in the management of
      smoking among inpatients.

PMID- 22372227
TI  - Completion of the statement of fitness for work: concise guidance.
AB  - Doctors are required to issue Form Med 3 (the Statements of Fitness for Work,
      commonly known as the fit note) where appropriate to patients for whom they
      provide clinical care. Much sickness absence is attributed to mild or moderate
      mental ill health, musculoskeletal or cardiorespiratory conditions. The effects
      of these conditions and others can often be accommodated at work, with
      appropriate adjustments, adaptations or support if necessary. Employers have a
      crucial role in achieving this; however, they need advice on the functional
      effects of the condition to do so. Evidence shows that work can be therapeutic
      and help promote recovery and rehabilitation. Conversely, unemployment is
      generally harmful to health and can lead to increased morbidity and poorer
      physical and mental health, as well as poverty, health inequalities and social
      exclusion. This concise guideline has been developed to aid doctors in
      understanding when and how to issue a fit note to the greatest benefit for their
      patients.

PMID- 22372228
TI  - Influenza-related pneumonia.
AB  - Influenza-related pneumonia encompasses both primary viral pneumonia and
      secondary bacterial pneumonia, which may be difficult to differentiate
      clinically. A high index of suspicion, prompt initiation of antiviral and
      antibiotic therapy, and appropriate escalation to secondary/critical care are key
      to improving outcome.

PMID- 22372229
TI  - Chronic obstructive pulmonary disease: consequences beyond the lung.

PMID- 22372230
TI  - Respiratory complications of obesity.

PMID- 22372231
TI  - Acute monitoring of patients with chronic respiratory disease during hospital
      admission.

PMID- 22372232
TI  - Pleural infection.

PMID- 22372233
TI  - Addison's disease masked by long-term exogenous steroid treatment for presumed
      polymyalgia rheumatica.

PMID- 22372234
TI  - Warfarin-induced skin necrosis.

PMID- 22372235
TI  - The Iatroversalia (doctor poems) of William Carlos Williams.

PMID- 22372236
TI  - Diagnostic support systems.

PMID- 22372237
TI  - Postgraduate training in global health: ensuring UK doctors can contribute to
      health in resource-poor countries.

PMID- 22372238
TI  - Paraneoplastic limbic encephalitis associated with ovarian teratoma.

PMID- 22372239
TI  - Autoimmune limbic encephalitis.

PMID- 22372240
TI  - The changing landscape of anticoagulation and atrial fibrillation.

PMID- 22372241
TI  - The cost of long hospital stays.

PMID- 22372242
TI  - Interface geriatrics: modernising conventional geriatric medical care.

PMID- 22372243
TI  - Inadvertent discovery of metastatic lung cancer: an unseen consequence of the
      introduction of specialist stroke units.

PMID- 22372244
TI  - The effects of Myxobolus cerebralis on the physiological performance of whirling
      disease resistant and susceptible strains of rainbow trout.
AB  - The development of rainbow trout Oncorhynchus mykiss strains that are resistant
      to whirling disease has shown promise as a management tool for populations in
      areas where Myxobolus cerebralis is present. However, the physiological effects
      of the disease on characteristics necessary for fish survival in natural river
      conditions have not been tested in many of these strains. Five rainbow trout
      strains were evaluated for their swimming ability and growth characteristics in
      relation to M. cerebralis exposure: the resistant German rainbow trout (GR)
      strain (Hofer strain), the susceptible Colorado River rainbow trout (CRR) strain,
      and three intermediate (hybrid) strains (F1 = GR x CRR; F2 = F1 x F1; B2 =
      backcross of F1 x CRR). Three broad response patterns among strain and exposure
      were evident in our study. First, exposure metrics, growth performance, and
      swimming ability differed among strains. Second, exposure to the parasite did not
      necessarily produce differences in growth or swimming ability. Exposure to M.
      cerebralis did not affect batch weight for any strain, and critical swimming
      velocity did not differ between exposed and unexposed families. Third, although
      exposure did not necessarily affect growth or swimming ability, individuals that
      exhibited clinical deformities did show reduced growth and swimming performance;
      fish with clinical deformities were significantly smaller and had lower critical
      swimming velocities than exposed fish without clinical deformities. Research and
      management have focused on GR x CRR hybrid strains; however, given the
      performance of the GR strain in our study, it should not be discounted as a
      potential broodstock. Additional field trials comparing the GR and F1 strains
      should be conducted before wholesale adoption of the GR strain to reestablish
      rainbow trout populations in Colorado.

PMID- 22372245
TI  - A real-time polymerase chain reaction assay for quantification of Edwardsiella
      ictaluri in catfish pond water and genetic homogeneity of diagnostic case
      isolates from Mississippi.
AB  - A quantitative polymerase chain reaction (qPCR) assay was developed for the
      detection and quantification of Edwardsiella ictaluri in channel catfish
      Ictalurus punctatus pond water using modifications to a published E. ictaluri
      specific qPCR assay and previously established protocols for the molecular
      detection of myxozoan parasites in catfish ponds. Genomic DNA equivalents
      indicative of the number of bacteria in a sample were determined and standard
      curves correlating to bacterial numbers were established. The assay was found to
      be highly repeatable and reproducible, with a linear dynamic range of five orders
      of magnitude. There was no interference of the assay from the presence of large
      quantities of nontarget DNA. Known quantities of bacteria were added to sample
      volumes of 40 or 500 mL of pond water collected from several different ponds. The
      minimum level of detection was approximately 100 cell equivalents (CE) in 40 (2.5
      CE/mL) or 500 mL of pond water (0.2 CE/mL). Sample volumes of 40 mL yielded the
      most consistent results, which were not significantly different from those
      obtained from broth culture alone. Cell equivalents determined by qPCR in 40-mL
      pond water samples spiked with known quantities of bacteria were within one order
      of magnitude of the actual number of cells added. Repetitive element-based
      polymerase chain reaction analysis of archived isolates demonstrated the genetic
      homogeneity of E. ictaluri, and consistent amplification of these isolates by
      qPCR analysis demonstrated the stability of the PCR target. The assay described
      here provides a reliable method for the detection and quantification of E.
      ictaluri in pond water and will be an invaluable tool in epidemiological studies.
      Additionally, the assay provides a way to evaluate the effects that vaccination,
      antibiotic treatments, and restricted feeding practices have on E. ictaluri
      populations during an outbreak. Information obtained with these tools will aid in
      optimizing disease management practices designed to maximize productivity while
      minimizing losses.

PMID- 22372246
TI  - Intersex condition of shoal bass in the Flint River, Georgia.
AB  - We examined male shoal bass Micropterus cataractae from the Flint River, Georgia,
      to determine the prevalence of intersex. During March and April 2010, we sampled
      61 shoal bass from six sites along the Flint River. Testes were examined
      histologically and classified as intersex if the presence of oocytes was noted.
      Using a severity index, we compared samples collected on different dates and from
      different locations according to age and testis weight. No significant variations
      were noted among any of the groupings. Further investigation is needed to
      determine whether the intersex condition in shoal bass is severe enough to
      warrant concern and whether it is a natural phenomenon.

PMID- 22372247
TI  - Modified live Edwardsiella ictaluri vaccine, AQUAVAC-ESC, lacks multidrug
      resistance plasmids.
AB  - Plasmid-mediated antibiotic resistance was first discovered in Edwardsiella
      ictaluri in the early 1990s, and in 2007 an E. ictaluri isolate harboring an
      IncA/C plasmid was recovered from a moribund channel catfish Ictalurus punctatus
      infected with the bacterium. Due to the identification of multidrug resistance
      plasmids in aquaculture and their potential clinical importance, we sought to
      determine whether the modified live E. ictaluri vaccine strain in AQUAVAC-ESC
      harbors such plasmids, so that the use of this vaccine will not directly
      contribute to the pool of bacteria carrying plasmid-borne resistance.
      Antimicrobial sensitivity testing of the E. ictaluri parent isolate and vaccine
      strain demonstrated that both were sensitive to 15 of the 16 antimicrobials
      tested. Total DNA from each isolate was analyzed by polymerase chain reaction
      (PCR) using a set of 13 primer pairs specific for conserved regions of the IncA/C
      plasmid backbone, and no specific products were obtained. PCR-based replicon
      typing of the parent isolate and vaccine strain demonstrated the absence of the
      18 commonly occurring plasmid incompatibility groups. These results demonstrate
      that the vaccine strain does not carry resistance to commonly used antimicrobials
      and provide strong support for the absence of IncA/C and other commonly occurring
      plasmid incompatibility groups. Therefore, its use should not directly contribute
      to the pool of bacteria carrying plasmid-borne resistance. This work highlights
      the importance of thoroughly investigating potential vaccine strains for the
      presence of plasmids or other transmissible elements that may encode resistance
      to antibiotics.

PMID- 22372248
TI  - Genotyping of infectious pancreatic necrosis virus isolates from Mexico state.
AB  - The infectious pancreatic necrosis virus (IPNV; genus Aquabirnavirus) affects
      salmon and trout, causing high mortality in first-feeding fry. The classification
      of this virus includes nine serotypes and seven genogroups. In Mexico, two
      different isolates were identified in 2000 and 2008, respectively. Both isolates
      were classified into genogroup I according to the RNA genome of this virus. As
      Mexico is importing rainbow trout Oncorhynchus mykiss eggs from different
      countries, the aim of this study was to genotype IPNV isolates obtained from four
      rainbow trout producer regions within the state of Mexico. We utilized a fragment
      of the VP2* (outer capsid protein) gene sequence of Mexican IPNV isolates as a
      molecular marker to determine the genogroup to which they belong. Although all
      Mexican IPNV isolates were grouped into genogroup I, we identified genetic
      diversity among these isolates, and 14 unique nucleotide sequence types were
      associated with the four producer regions in Mexico State.

PMID- 22372249
TI  - Detection of viral hemorrhagic septicemia virus by quantitative reverse
      transcription polymerase chain reaction from two fish species at two sites in
      Lake Superior.
AB  - Viral hemorrhagic septicemia virus (VHSV) was first detected in the Laurentian
      Great Lakes in 2005 during a mortality event in the Bay of Quinte, Lake Ontario.
      Subsequent analysis of archived samples determined that the first known isolation
      of VHSV in the Laurentian Great Lakes was from a muskellunge Esox masquinongy
      collected in Lake St. Clair in 2003. By the end of 2008, mortality events and
      viral isolations had occurred in all of the Laurentian Great Lakes except Lake
      Superior. In 2009, a focused disease surveillance program was designed to
      determine whether VHSV was also present in Lake Superior. In this survey, 874
      fish from 7 sites along the U.S. shoreline of Lake Superior were collected during
      June 2009. Collections were focused on nearshore species known to be susceptible
      to VHSV. All fish were dissected individually by using aseptic techniques and
      were tested for the presence of VHSV genetic material by use of a quantitative
      reverse transcription (qRT) polymerase chain reaction (PCR) targeting the viral
      nucleoprotein gene. Seventeen fish from two host species at two different sites
      tested positive at low levels for VHSV. All attempts to isolate virus in cell
      culture were unsuccessful. However, the presence of viral RNA was confirmed
      independently in five fish by using a nested PCR that targeted the glycoprotein
      (G) gene. Partial G gene sequences obtained from three fish were identical to the
      corresponding sequence from the original 2003 VHSV isolate (MI03) from
      muskellunge. These detections represent the earliest evidence for the presence of
      VHSV in Lake Superior and illustrate the utility of the highly sensitive qRT-PCR
      assay for disease surveillance in aquatic animals.

PMID- 22372250
TI  - Concentration of infectious aquatic rhabdoviruses from freshwater and seawater
      using ultrafiltration.
AB  - Infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia
      virus, and spring viremia of carp virus were concentrated and detected from
      freshwater and seawater samples by using hollow-fiber ultrafiltration. Within 60
      min, virus in a 50-L freshwater or saltwater sample was concentrated more than 70
      fold, and virus retention efficiencies were consistently greater than 88%.
      Retention efficiency was highly dependent upon concentrations of column blocking
      and sample stabilization solutions. A large column with a surface area of 1.15 m2
      and a filtration capacity of 5-200 L exhibited optimal viral retention when
      blocked with 2% fetal bovine serum (FBS) and when the samples were supplemented
      with 0.1% FBS. Conversely, a small column with 100-fold less surface area and a
      filtering capacity of 0.5-2.0 L was optimized when blocked with 1% FBS and when
      the samples were supplemented with 0.1% FBS. The optimized ultrafiltration
      procedure was further validated with water from a tank that contained IHNV
      exposed juvenile sockeye salmon Oncorhynchus nerka, resulting in an average virus
      retention efficiency of 91.6 +/- 4.1% (mean +/- SE). Virus quantification of
      concentrated samples demonstrated that IHNV shedding in sockeye salmon preceded
      mortality; shedding of the virus was observed to increase significantly as early
      as 7 d postchallenge and peaked at day 14, when virus levels reached 4.87 x 10(3)
      plaque-forming units/mL. We conclude that ultrafiltration is a reliable and
      effective method for concentrating viable aquatic rhabdoviruses from large
      volumes of water and has application for the analysis of environmental water
      samples.

PMID- 22372251
TI  - Spreading a medication administration intervention organizationwide in six
      hospitals.
AB  - BACKGROUND: Six hospitals from the San Francisco Bay Area participated in a 12
      month quality improvement project conducted by the Integrated Nurse Leadership
      Program (INLP). A quality improvement intervention that focused on improving
      medication administration accuracy was spread from two pilot units to all
      inpatient units in the hospitals. METHODS: INLP developed a 12-month curriculum,
      presented in a combination of off-site training sessions and hospital-based
      training and consultant-led meetings, to teach clinicians the key skills needed
      to drive organizationwide change. Each hospital established a nurse-led project
      team, as well as unit teams to address six safety processes designed to improve
      medication administration accuracy: compare medication to the medication
      administration record; keep medication labeled throughout; check two patient
      identifications; explain drug to patient (if applicable); chart immediately after
      administration; and protect process from distractions and interruptions. RESULTS:
      From baseline until one year after project completion, the six hospitals improved
      their medication accuracy rates, on average, from 83.4% to 98.0% in the spread
      units. The spread units also improved safety processes overall from 83.1% to
      97.2%. During the same time, the initial pilot units also continued to improve
      accuracy from 94.0% to 96.8% and safety processes overall from 95.3% to 97.2%.
      CONCLUSION: With thoughtful planning, engaging those doing the work early and
      focusing on the "human side of change" along with technical knowledge of
      improvement methodologies, organizations can spread initiatives enterprisewide.
      This program required significant training of frontline workers in problem
      solving skills, leading change, team management, data tracking, and
      communication.

PMID- 22372252
TI  - Improving venous thromboembolism prevention processes and outcomes at a community
      hospital.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a cause of significant morbidity and
      mortality in hospitalized patients in the United States. Quality improvement (QI)
      strategies to increase the rates of prophylaxis in patients at-risk for VTE have
      been shown to be successful. The development of a formal, active strategy
      addressing the prevention of VTE, as a written, institutionwide VTE prophylaxis
      policy, presents a challenge for hospitals METHODS: In 2007 a multidisciplinary
      VTE committee was initiated to develop and implement a hospitalwide QI program to
      standardize VTE risk assessment and prophylaxis prescribing practices at Saint
      Francis Hospital (Tulsa, Oklahoma). The QI program included clinician education,
      VTE order set and electronic trigger implementation, and changes in mechanical
      prophylaxis usage. RESULTS: The VTE prophylaxis order set was successfully
      piloted and implemented hospitalwide within three months of the project's
      initiation. Standardization of VTE prophylaxis practices across surgical and
      medical specialties was the key aim of this QI program. As a result, patient
      related outcomes were also improved. The number of hospital-acquired VTE events
      decreased from 123 (0.39%) in 2008 to 99 (0.32%) in 2009 and 87 (0.27%) in 2010,
      and a reduction in the VTE rate between 2008 and 2010 of 31.6%. There was a
      significant decrease between 2008 and 2010 in the number of hospital-acquired VTE
      events (p = .035). CONCLUSIONS: Keys to the success of this QI program included
      leveraging multidisciplinary VTE committee members, physician champions, multiple
      approaches to communication and education, and providing evidence to support the
      changes. Sharing the hospital's QI process may provide a model for other
      hospitals challenged with developing and sustaining positive outcomes in patients
      at risk for VTE.

PMID- 22372253
TI  - Estimated costs associated with improving influenza vaccination for health care
      personnel in a multihospital health system.
AB  - BACKGROUND: Health care personnel (HCP) are an important target group for
      influenza vaccination because of their close contact with vulnerable patients.
      Annual influenza vaccination for HCP is recommended to reduce the spread of
      influenza and decrease staff illness and absenteeism. UPMC Health System, the
      largest health system in western Pennsylvania, established a quality improvement
      project to increase influenza vaccination among its > 50,000 employees by
      implementing survey-informed interventions. At the completion of the
      intervention, estimates were prepared of the costs associated with implementing a
      multifaceted quality improvement intervention to improve HCP influenza
      vaccination rates in a large multihospital health system. METHODS: All 11
      participating hospitals provided education and publicity regarding influenza
      vaccination and provided vaccine free of charge at mass vaccination clinics. Two
      additional strategies-mobile vaccination carts and incentives-were implemented in
      a factorial design such that the hospitals had either carts, incentives, both
      strategies, or neither. The minimum and maximum costs per vaccinated employee by
      type of intervention were estimated using cost data for vaccine/supplies, labor,
      incentives, and administration. RESULTS: The average costs per vaccinated
      employee ranged from $24.55 to $30.43 for incentives and carts, $20.66 to $25.57
      for incentives, $23.24 to $26.54 for carts, and $18.03 to $20.60 for education
      and publicity only. Vaccination rates increased significantly but remained below
      ideal levels. CONCLUSIONS: Influenza vaccination rates among nonphysician HCP can
      be improved using various interventions at a low cost per vaccinated employee.
      The costs for these nonmandatory interventions were modest compared with the
      costs typically associated with influenza-related absenteeism.

PMID- 22372254
TI  - Ongoing professional performance evaluation (OPPE) using automatically captured
      electronic anesthesia data.
AB  - BACKGROUND: The Massachusetts General Hospital (Boston), a large academic center
      providing anesthesia services for more than 49,000 procedures each year, created
      an Ongoing Professional Practice Evaluation (OPPE) process that could use readily
      available, automatically captured electronic information from its vendor-provided
      anesthesia information management system. METHODS: The OPPE credentialing
      committee selected the following initial metrics: Blood pressure (BP) monitoring,
      end tidal CO2 monitoring, and timely documentation of compliance statements.
      Baseline data on the metrics were collected in an eight-month period (January 1,
      2008-August 31, 2008). In February 2009 information on the metrics was provided
      to the department's staff members, and the ongoing evaluation process began. On
      the basis of three months of data, final reports for physicians being
      credentialed were distributed. Each report included a listing for each metric of
      the total number of compliant cases and noncompliant cases and a comparison by
      percentage to the baseline departmental evaluation. A summary statement indicated
      whether a physician's performance was within the group representing 95% of all
      department physicians. Noncompliant cases were listed by medical record number
      and case date so providers and reviewers could examine individual cases.
      CONCLUSION: A novel, automated, and continuous reporting system for physician
      credentialing that uses the existing clinical information system infrastructure
      can serve as a key element of a comprehensive clinical performance evaluation
      that measures both technical and generalizable clinical skill sets. It is not
      intended to provide a complete system for measuring competence but rather to
      serve as a first-round warning mechanism and metric scoring tool to identify
      problems and potential performance noncompliance issues.

PMID- 22372255
TI  - Impact of an easy-access telephonic interpreter program in the acute care
      setting: an evaluation of a quality improvement intervention.
AB  - BACKGROUND: Language barriers render interaction with the health care system
      difficult and lead to health disparities for patients with limited English
      proficiency (LEP). Despite a long-standing legal obligation for large health care
      organizations in the United States to try to provide free language access
      services for patients with LEP, professional interpretation is not always widely
      accessible, and even when it is, its use is often suboptimal. A dual-handset
      phone with 24-hour access to professional telephonic interpretation was placed at
      the bedside of all patients admitted to the general medicine floor of a tertiary
      care academic hospital. METHODS: Nurses and physicians were surveyed before and
      after the easy-access interpretation program's implementation. RESULTS:
      Distribution of pre- and postimplementation surveys to 127 and 122 nurses,
      respectively, yielded a total of 163 completed surveys (overall participation
      rate, 65%). Distribution of surveys to 96 and 78 physicians, respectively,
      yielded 116 completed surveys (overall participation rate, 67%). After
      implementation, use of professional telephonic interpreters for communication
      with LEP patients increased fourfold, without a decrease in use of professional
      in-person interpreters. There were significant increases in professional
      interpreter use during brief communications with high error potential, including
      medication administration (odds ratio [OR] = 1.9, 95% confidence interval [CI]
      1.1-3.2) and pre-rounding (OR = 3.4, 95% CI 1.2-9.8). CONCLUSIONS: Increasing
      ease of access to dual-handset interpreter telephones promotes use of
      professional interpreters in the acute care setting. Future hospital policy
      should focus on further integrating language services into the hospital
      environment, accompanied by an educational program to assist in shifting
      professional norms toward use of professional interpreters.

PMID- 22372256
TI  - Accelerating what works: using qualitative research methods in developing a
      change package for a learning collaborative.
AB  - BACKGROUND: Learning (quality improvement) collaboratives are effective vehicles
      for driving coordinated organizational improvements. A central element of a
      learning collaborative is the change package-a catalogue of strategies, change
      concepts, and action steps that guide participants in their improvement efforts.
      Despite a vast literature describing learning collaboratives, little to no
      information is available on how the guiding strategies, change concepts, and
      action items are identified and developed to a replicable and actionable format
      that can be used to make measurable improvements within participating
      organizations. METHODS: The process for developing the change package for the
      Health Resources and Services Administration's (HRSA) Patient Safety and Clinical
      Pharmacy Services Collaborative entailed environmental scan and identification of
      leading practices, case studies, interim debriefing meetings, data synthesis, and
      a technical expert panel meeting. Data synthesis involved end-of-day debriefings,
      systematic qualitative analyses, and the use of grounded theory and inductive
      data analysis techniques. This approach allowed systematic identification of
      innovative patient safety and clinical pharmacy practices that could be adopted
      in diverse environments. A case study approach enabled the research team to study
      practices in their natural environments. Use of grounded theory and inductive
      data analysis techniques enabled identification of strategies, change concepts,
      and actionable items that might not have been captured using different
      approaches. DISCUSSION: Use of systematic processes and qualitative methods in
      identification and translation of innovative practices can greatly accelerate the
      diffusion of innovations and practice improvements. This approach is effective
      whether or not an individual organization is part of a learning collaborative.

PMID- 22372257
TI  - Dental management of Parkinson's disease.

PMID- 22372258
TI  - Expanding prosthodontic services to the older patient in dental practices.
AB  - Numerous articles report on the unmet dental needs of the older patient, yet few
      have suggested strategies to overcome barriers to care for this unique
      demographic. At a time when prosthodontic services, including dental implants,
      offer improved outcomes, the elderly remain the least served of all patient
      groups. Obstacles to treatment include ageism, medical and dental complexity,
      financial limitations, and patients' resistance to treatment. Expanding
      prosthodontic care of the elderly requires a departure from traditional patient
      management techniques. The attempt to reverse ageism in your practice must go
      beyond simple awareness. Those offices that can relate to, treat with respect,
      and fulfill the health aspirations of the older patient create the atmosphere
      where care is more readily accepted. A successful team approach to patient
      management depends upon the ability to listen and respond to the elderly denture
      patient with information on denture maintenance and implant enhancements. An
      essential piece is encouraging regular recall for all denture wearers by every
      staff member. A well documented problem area in dental practice is the timely
      replacement of worn out or inadequate dentures. By using a simple assessment tool
      called the Satisfaction/Condition Score along with motivational interviewing, we
      have found increased treatment acceptance among our existing patients. Use of
      these suggestions in a general dentistry practice is more likely to encourage the
      older patient to better accept enhanced prosthodontic services.

PMID- 22372259
TI  - Something beautiful.

PMID- 22372260
TI  - Navigating the investment landscape: why every dentist needs an investment policy
      statement.

PMID- 22372261
TI  - Safe patient handling. Interview by Steve Shuman and Peg Simonson.

PMID- 22372262
TI  - What's a dentist to do? The search for meaning.

PMID- 22372263
TI  - Cleanliness is next to godliness?

PMID- 22372264
TI  - The effect of fluoride on orthodontic tooth movement in humans. A two- and three
      dimensional evaluation.
AB  - AIMS: The aim of the present study was to determine whether high and low fluoride
      concentrations in drinking water affected the early stages of tooth movement when
      heavy and light orthodontic forces were applied for 4 weeks. A further aim was to
      compare and evaluate the resulting two-dimensional (2-D) and three-dimensional (3
      D) orthodontic tooth movement. METHODS: The sample consisted of 96 maxillary
      upper first premolars from 48 patients who required premolar extractions as part
      of their orthodontic treatment. Patients were selected from two different cities
      in Turkey with low and high fluoride concentrations of 0.05 and 2 ppm,
      respectively. The patient sample was divided into four groups according to the
      magnitude of force applied to the first premolars and the concentration of
      fluoride in the public water supply; Group 1, High fluoride intake (> or = 2 ppm)
      Heavy force (225 g); Group 2, Low fluoride intake (< or = 0.05 ppm)-Heavy force;
      Group 3, High fluoride intake-Light force (25 g); and Group 4, Low fluoride
      intake-Light force. A light or heavy buccal tipping orthodontic force was applied
      to the upper first premolars for 4 weeks. The first three palatal rugae were used
      for the superimposition of patient casts in a 2-D and 3-D evaluation of generated
      movements. RESULTS: It was found that heavy force application and fluoride intake
      increased the average rate of tooth movement. It was further shown that age was
      negatively correlated with tooth movement in the 2-D and 3-D measurements.
      CONCLUSIONS: The average rate of tooth movement was found to be greater in the
      heavy force and high fluoride intake group (Group 1HH). Age was negatively
      correlated with orthodontic tooth movement. Two- and three-dimensional methods
      were accurate for the assessment of tooth movement after four weeks of buccal
      tipping force application when the palatal rugae were used for superimposition.

PMID- 22372265
TI  - The presence of TNF-alpha and TNFR1 in aseptic root resorption. A preliminary
      study.
AB  - BACKGROUND: It is hypothesised that osteoprotegerin (OPG), as an osteoclast
      antagonist, may offer molecular control over the process of orthodontic root
      resorption. Previous work investigating OPG in a rat periodontal ligament (PDL)
      ankylosis model found no inhibitory effect on osteoclasts and odontoclasts when
      given at a recommended dosage of 2.5 mg/kg. It was considered that traumatically
      induced PDL inflammation produces mediators and cytokines with the ability to
      stimulate clast cell differentiation and counter the effects of OPG. AIMS: The
      present study investigated the presence of Tumour Necrosis Factor Alpha (TNF
      alpha) and its receptor Tumour Necrosis Factor Receptor 1 (TNFR1) in a PDL
      sterile inflammatory model. METHODS: Dry ice was applied for 15 minutes to the
      upper right first molar crown of eighteen, 8-week-old, male Sprague-Dawley rats
      of which 9 were injected with OPG at a dose of 2.5 mg/kg of body weight at the
      time of freezing. After 7 days, the rats were sacrificed and each maxilla
      processed for immunohistochemical identification of TNF-alpha and TNFR1. RESULTS:
      Results showed the presence of root resorption in varying amounts and locations
      in both experimental and control rats. Reparative processes appeared greater in
      the OPG-treated rats, often with the presence of an ankylotic union.
      Immunolabelling showed the presence of TNF-alpha and TNFR1 in the sterile
      inflammation located mainly in the interradicular PDL area. More definitive
      labelling appeared in OPG-treated rats. CONCLUSION: The results indicated that
      TNF-alpha, and its receptor TNFR1, by their presence, may modify OPG
      effectiveness by offering an alternative pathway for osteoclast formation, which
      counters the anti-resorptive effects of OPG.

PMID- 22372266
TI  - Comparison of the effects of fixed and removable functional appliances on the
      skeletal and dentoalveolar structures.
AB  - OBJECTIVE: To compare and analyse the effects of activator and Forsus FRD EZ
      appliances in the treatment of skeletal Class II division I malocclusion.
      METHODS: Lateral cephalograms and hand-wrist radiographs were collected from 24
      Class II division I growing patients (14 females, 10 males). The patients were
      randomly divided into two equal groups and either treated with an activator
      appliance (Mean age 12.67 +/- 1.24 years) or with a Forsus FRD EZ appliance (Mean
      age 12.31 +/- 1.09 years). Pretreatment and posttreatment cephalometric
      radiographs were obtained, traced, superimposed and data analysed using paired t
      tests and the Wilcoxon signed rank test. RESULTS: The results demonstrated that
      the Forsus FRD EZ effectively corrected the Class II malocclusion, but the
      changes were mainly dentoalveolar. The Forsus FRD EZ appliance induced a
      clockwise rotation of the occlusal plane without significant alteration in the
      vertical facial dimension. Skeletally, maxillary growth was restricted and
      pogonion moved forward which improved the profile. CONCLUSION: The Forsus FRD EZ
      appliance may be an effective dentoalveolar treatment method to manage a skeletal
      imbalance and improve the profile in growing patients.

PMID- 22372267
TI  - New clinical classification of dental arch form using facial axis points derived
      from three-dimensional models.
AB  - INTRODUCTION: The purpose of the present study was to use facial axis (FA) points
      to classify dental arch form generated from an analysis of 3-D virtual models of
      a sample of normal occlusions. A secondary aim was to introduce a new arch form
      template based on this classification for clinical application. METHODS: One
      hundred and twenty five plaster models of Class I occlusions were 3-D scanned
      (Orapix Co., Ltd, Seoul, Korea) and FA points digitized on the virtual models
      using Rapidform 2006 software (INUS Technology Inc., Seoul, Korea). Following
      intercanine and intermolar arch width and depth measurements, K-means cluster
      analysis was applied on 77 cases (Dataset 1) to classify the sample into arch
      form types. A curve of best fit of the mean arch form of each type was generated.
      The remaining 48 cases (Dataset 2) were mapped into the clusters and a
      multivariate test was performed to assess the differences among the clusters.
      RESULTS: Classification into five clusters demonstrated maximum inter-cluster
      distance in the arch parameters and produced the most homogeneous cluster size.
      The differences between the 5 cluster types were statistically but not clinically
      significant and so they were recombined to form three clusters representing
      'narrow', 'moderate' and 'wide' arch forms. CONCLUSIONS: A template with three
      arch form types based on anterior and posterior dimensions has been proposed
      through 3-D analysis of FA points for more accurate arch form identification and
      arch wire selection.

PMID- 22372268
TI  - Finite element method (FEM) analysis of the force systems produced by asymmetric
      inner headgear bows.
AB  - BACKGROUND: Extra-oral traction appliances were introduced more than a century
      ago and continue to be used to produce orthopaedic and/or dental changes in the
      maxilla. While force systems produced by asymmetric outer bows have been studied
      extensively, the force systems produced by asymmetric inner bows have been
      overlooked. AIM: To analyse the forces acting on the maxillary first molars: when
      the size of one bayonet bend is increased; when the point of application of the
      distalising force on the inner bow is moved to one side; when one molar is
      displaced palatally. METHODS: Four FEM models of cervical headgear attached to
      maxillary first molars were designed in SolidWorks 2010 and transferred to an
      ANSYS Workbench Ver. 12.1. Model 1, each molar was 23 mm from the midpalatal line
      and the inner bow was symmetrical; Model 2, the left molar was displaced 4 mm
      towards the midpalatal line and the inner bow was symmetrical; Model 3, the
      molars were equidistant (23 mm) from the midpalatal line, but the left molar was
      engaged by a 2 mm larger bayonet bend; Model 4, the molars were equidistant (23
      mm) from the midpalatal line but the join between the inner and outer bows was
      displaced 2 mm towards the left molar. In all FEM models, a 2N force was applied
      to the inner bow at the join between inner and outer bows and the energy
      transmitted to the teeth and the von Mises stresses on the molar PDLs were
      assessed. RESULTS: There were marked differences in the strain energy on the
      teeth and the von Mises stresses on their PDLs. A 14 to 20 per cent increase in
      energy and force was produced on the tooth closer to the symmetric plane of the
      headgear. In addition, the increase in energy produced a 30 to 62 per cent
      increase in the von Mises stresses within the PDLs. CONCLUSION: Small asymmetries
      in molar position, the size of a bayonet bend and the point of application of a
      force on an inner bow resulted in asymmetrical forces on the molars. These forces
      were higher on the molar closer to the symmetric plane of the headgear.

PMID- 22372269
TI  - The effects of lubrication on the static frictional resistance of orthodontic
      brackets.
AB  - BACKGROUND: Difficulties are experienced with the collection and storage of
      freshly harvested human saliva to use as a lubricant for the laboratory testing
      of the frictional resistance of orthodontic brackets. In order to overcome these
      difficulties, researchers have suggested the use of saliva substitutes due to
      their ease of storage and consistency of properties throughout testing. Others
      have criticized the use of artificial saliva and prefer the dry state. The
      present study aimed to compare the effects of human saliva and an artificial
      saliva (Saliva Orthana) with the dry state for the static frictional resistance
      testing of orthodontic brackets. METHODS: The static frictional resistance and
      the lubrication effect of human saliva, Saliva Orthana and the dry state were
      investigated using upper central incisor stainless steel brackets and 0.019 x
      0.025 inch stainless steel wires in an Instron Universal Testing Machine. Static
      frictional resistance was measured 100 times for each lubrication state. The
      'wettability' of each lubricant was determined by measuring the contact angle
      against a stainless steel surface using the CAM 200 Optical Contact Angle Meter.
      Distilled water acted as a control. The viscosity of each lubricant and their
      Newtonian or non-Newtonian fluid behaviour under stress was measured using a
      Brookfield Digital Rheometer Model DV-III+. RESULTS: The differences in static
      frictional resistance between the three lubricants when examined as a group did
      not reach statistical significance (p = 0.059). The difference between human
      saliva and Saliva Orthana was considered to be of weak statistical significance
      and clinical relevance (Means: 0.917 N; 0.819 N: p = 0.053). Human saliva and the
      dry state revealed very similar mean frictional values (Means: 0.917 N; 0.875 N:
      p = 0.932). The contact angle tests indicated a statistically significant
      difference between the lubricants with Saliva Orthana having the smallest angle
      and therefore the highest 'wettability'. Human saliva had the highest initial
      viscosity and behaved as a non-Newtonian fluid, contrasting with Saliva Orthana
      and distilled water, both of which behaved as Newtonian fluids. CONCLUSION: The
      current results indicate that artificial saliva is not an ideal alternative to
      human saliva for friction testing in the laboratory The results therefore support
      the proposal that, when human saliva is not available, it may be preferable to
      test orthodontic frictional resistance in the dry state.

PMID- 22372270
TI  - Bond failure rates of two self-ligating brackets: a randomised clinical trial.
AB  - AIMS: To evaluate the bond failure rates of two self-ligating appliance systems
      bonded with a self-etching primer. METHODS: Forty patients were randomly assigned
      to either Group SC (SmartClip, 3M Unitek, Monrovia, CA, USA) or Group IR (In
      Ovation R, GAC International, Bohemia, NY, USA) appliance groups. Seven hundred
      and sixty six brackets were bonded with Transbond Plus Self-Etching Primer and
      Transbond Plus Color Change Adhesive according to the manufacturer's
      instructions. Over a 12-month period, the survival rates of the brackets were
      estimated with the Kaplan-Meier analysis. The survival distributions for the
      appliance systems, dental arch and position in the dental arch were compared with
      the log-rank test. RESULTS: The bond failure rate for SC was significantly lower
      than IR (p = 0.022). There were no differences in failure rates between either
      the maxillary and mandibular arches or between the anterior and posterior
      brackets. CONCLUSION: SC provided a more reliable bond than IR over the 12-month
      observation period, however, both brackets had clinically acceptable bond failure
      rates.

PMID- 22372271
TI  - Orthodontic treatment provision and referral preferences among New Zealand
      general dental practitioners.
AB  - BACKGROUND: General dental practitioners (GDPs) are key clinicians in the
      orthodontic referral chain as they complement (and may compete with)
      orthodontists in providing treatment for the public. OBJECTIVES: To determine the
      nature and extent of GDPs' involvement in orthodontic treatment provision and to
      identify influences on GDPs' choice of orthodontist. METHODS: An email survey was
      conducted of actively-practising GDPs in May-June 2010. Two timelines of contact
      were followed, with non-responders to the first survey re-contacted three weeks
      later. RESULTS: Just under one-fifth (19.3 per cent) reported providing forms of
      orthodontic treatment. This proportion was higher among males, more experienced
      practitioners, and dentists in rural locations. The percentage involvement ranged
      from 22.3 per cent in Greater Auckland to 10.5 per cent in Greater Wellington and
      11.9 per cent in Christchurch. In the remainder of New Zealand, percentages
      ranged from 11.5 per cent in urban areas to 37.1 per cent in rural areas. Of
      those providing treatment, almost half had 1-10 patients under management, and
      just over one-third had greater numbers. Sixty-one per cent of orthodontically
      involved GDPs in Auckland had more than 10 orthodontic patients. The most
      commonly treated condition was a simple crossbite, while the least commonly
      treated condition was the severe Class III malocclusion. CONCLUSIONS: The
      provision of orthodontic treatment by New Zealand GDPs has decreased in recent
      years to an average of about one in five, but this figure is considerably higher
      in rural areas and is a notable feature of the greater Auckland area. The
      findings suggest that the majority of the more complex cases are continuing to be
      referred to specialist orthodontists.

PMID- 22372272
TI  - Differences in dentofacial characteristics between southern versus northern
      Chinese adolescents.
AB  - AIM: To compare the dentofacial characteristics of southern and northern Chinese
      adolescents. METHODS: A southern Chinese sample comprised 70 males (Mean age 12.4
      +/- 0.60 years) and 60 females (Mean age 12.5 +/- 0.4 years), and a northern
      Chinese sample consisted of 50 males (Mean age 12.8 +/- 1.8 years) and 50 females
      (Mean age 12.4 +/- 1.2 years). All subjects had a Class I molar relationship with
      no or minimal crowding, a well balanced cephalometric profile, and no history of
      orthodontic treatment. Patient cephalograms were traced and digitized and
      McNamara's analysis applied. RESULTS: A smaller midface and a shorter overall
      mandibular length were observed in southern Chinese, whereas significantly
      increased vertical dimension and a retrusive chin were noted in northern Chinese.
      Protrusive upper and lower incisors and a protrusive upper lip were found in
      southern Chinese. CONCLUSIONS: There were significant differences in dentofacial
      morphology between southern and northern Chinese adolescents. It is suggested
      that separate cephalometric norms be used for patients originating from different
      parts of China.

PMID- 22372273
TI  - A comparative diagnostic assessment of anterior tooth and bone status using
      panoramic and periapical radiography.
AB  - AIMS: The aim of the present study was to compare diagnostic assessments of
      anterior tooth and bone status in a randomised cohort of pre-orthodontic patients
      using panoramic and periapical radiographs. METHOD: Four hundred and forty-four
      cases with matched periapical and panoramic radiographs were examined by three
      observers. Two were final-year postgraduate endodontic students and the other, a
      final-year Honours degree dental student. Multi-rater Kappa values were used to
      assess the reliability of the observers, with a value of 1 equating to complete
      agreement. RESULTS: With the exception of endodontic Class 1 and 2 palatal
      invaginations, reliability exceeded 0.95 for all three observers. An assessment
      of the graduate endodontic students revealed only a marginal increase in the
      kappa values. Statistical analysis (p < 0.05) determined that developmental
      anomalies or tooth/bone pathoses were more reliably detected by observers using
      periapical radiographs compared with panoramic films. This finding has relevance
      given the likelihood of anterior dental trauma among young children. CONCLUSION:
      While there have been considerable improvements in the quality of dental
      panoramic radiography, the present study indicated that a reliable pre
      orthodontic or post-trauma diagnostic assessment should include both panoramic
      and intra-oral radiographs.

PMID- 22372274
TI  - Changes in malocclusion over time in New Zealand adolescents.
AB  - BACKGROUND: The Dental Aesthetic Index (DAI) has been used in many cross
      sectional studies of population samples, but its use in assessing changes in
      malocclusion is less common. The aim of the present study was to describe the
      natural history of malocclusion and investigate the utility of the DAI as a
      measure for describing changes in malocclusion in a population-based sample of
      adolescents. METHOD: A repeat examination was conducted of a sample of 430
      children first assessed in 2003 at age 13 and re-examined at age 16 (255 or 59.3
      per cent of the baseline sample) with their DAI and orthodontic history recorded
      at each age. RESULTS: Of the adolescents re-assessed, 28 were in active
      orthodontic treatment, 30 had completed treatment and 197 had not received any
      treatment. There were substantial changes in the DAI items from age 13 to 16,
      with the greatest improvement in maxillary anterior irregularity. Overall, almost
      one-quarter of participants showed an improvement in their DAI treatment need
      category which was considerably higher among those who had either received
      treatment or were in treatment. CONCLUSION: The DAI is a valid and responsive
      tool for measuring change in malocclusion over time. Anterior mandibular
      irregularity shows the greatest change with age, and orthodontic treatment is
      effective in treating malocclusion, at least in the short-term.

PMID- 22372275
TI  - Long-term follow up of clinical outcome of orthodontic tooth movement following
      extraction of previously auto-transplanted maxillary canines and bone grafting: a
      case report.
AB  - BACKGROUND: The present case is a 13-year follow up of a patient in which the
      treatment plan involved removal of unsatisfactory auto-transplanted maxillary
      canines together with a bone graft to re-establish normal dento-alveolar ridge
      morphology. Active tooth movement occurred in the graft site. At the time, this
      was a new approach and there was no information in the literature as to the
      outcome of this treatment modality. Long-term reports regarding the success of
      this treatment are lacking. AIMS: To assess the long-term outcome of active tooth
      movement into a site that required bone grafting. METHODS: The upper right canine
      was non-vital with poor periodontal support on its buccal aspect. Examination
      revealed a substantial bony defect with a loss of the buccal cortical plate
      following extraction. To augment the ridge defect bone was taken from the
      maxillary tuberosity and grafted in the upper right canine extraction site and
      fixed with a bone screw. Protraction of the first premolar and retraction of the
      lateral incisor into the graft site was slow and constant. RESULTS: Significant
      closure of the upper canine extraction space was achieved. There were no
      significant detrimental bone changes in the interproximal areas of 14 and 12.
      CONCLUSION: By employing a bone graft to reestablish alveolar bone prior to tooth
      movement, excellent bone support, periodontal health and a long-term stable
      result were obtained.

PMID- 22372276
TI  - Management of severe Class II division 1 malocclusion: a case report.
AB  - AIMS: To describe the two-phase treatment of a preadolescent boy with a severe
      skeletal Class II division 1 malocclusion with vertical maxillary excess and
      spaced upper incisors. METHODS: Treatment involved an orthopaedic phase using
      high-pull headgear and a maxillary intrusion splint followed by non-extraction
      orthodontic treatment with a pre-adjusted edgewise appliance. The case was
      assessed at the start of treatment (T1), at the end of orthopaedic treatment
      (T2), at the end of orthodontic treatment (T3) and 2 years after debanding (T4).
      RESULTS: At T2 the Class II molar occlusion was corrected to a Class I molar
      relationship and the overjet and overbite were considerably reduced. A lower lip
      trap was relieved and a normal mentolabial sulcus obtained. The cephalometric
      changes at T2 revealed a 4 degree reduction in the ANB angle but no change in the
      SNA angle. At T3, the inclination of the upper central incisors, the overjet and
      overbite were normal and the spaces between the upper anterior teeth were closed.
      At T4, the Class I molar and canine relationships, reduced overjet, reduced
      overbite and intercuspation were maintained. The curve of Spee deepened slightly.
      CONCLUSION: A severe skeletal Class II division 1 malocclusion with vertical
      maxillary excess may be successfully treated in two phases with an initial
      orthopaedic appliance in the form of high-pull head gear and a maxillary
      intrusion splint followed by fixed appliances.

PMID- 22372277
TI  - When sample size calculation makes the difference.

PMID- 22372278
TI  - Reality-relapse-retention (3Rs).

PMID- 22372279
TI  - Does "spiritual" indicate a limit to palliative care?

PMID- 22372280
TI  - Bereaved family members' assessments of the quality of end-of-life care: what is
      important?
AB  - Families of patients are well poised to comment on the end-of-life (EOL) care
      received by those patients and can provide feedback to care providers and
      decision makers. To better understand family-member evaluations of the quality of
      in-patient EOL care, this study draws on qualitative interview data (n = 24) to
      identify core aspects of EOL care that are important for family members. Based on
      this analysis, a conceptual framework of family members' assessments of their
      experiences with EOL health care services is developed. Findings suggest the need
      to distinguish between perceived substantive or tangible features of received
      care, interpretations of the causes and symbolic meanings of that care, and
      personal and affective outcomes. Practitioners are encouraged to reflect on how
      behaviours and communications may be interpreted by families. Attention also
      needs to be given to the changes in practice and organizational decision making
      that can facilitate more positive experiences for families and patients.

PMID- 22372281
TI  - Evaluating program integration and the rise in collaboration: case study of a
      palliative care network.
AB  - INTRODUCTION: There is increasing global interest in using regional palliative
      care networks (PCNs) to integrate care and create systems that are more cost
      effective and responsive. We examined a PCN that used a community development
      approach to build capacity for palliative care in each distinct community in a
      region of southern Ontario, Canada, with the goal of achieving a competent
      integrated system. METHODS: Using a case study methodology, we examined a PCN at
      the structural level through a document review, a survey of 20 organizational
      administrators, and an interview with the network director. RESULTS: The PCN
      identified 14 distinct communities at different stages of development within the
      region. Despite the lack of some key features that would facilitate efficient
      palliative care delivery across these communities, administrators largely viewed
      the network partnership as beneficial and collaborative. CONCLUSION: The PCN has
      attempted to recognize specific needs in each local area. Change is gradual but
      participatory. There remain structural issues that may negatively affect the
      functioning of the PCN.

PMID- 22372282
TI  - End-of-life care for the dying child: what matters most to parents.
AB  - OBJECTIVE: To identify and define the dimensions of pediatric end-of-life (EOL)
      care that are important to parents. POPULATION: Parents of children who died as a
      result of an illness, chronic condition, or birth defect while receiving EOL care
      in hospital or at home in 2004 and 2005. DESIGN: Qualitative data derived from
      semi-structured and focus group interviews were analyzed using content analysis.
      SETTING: A large pediatric hospital located in the Midwestern United States.
      RESULTS: Seven dimensions of pediatric EOL care were identified--respect for the
      family's role, comfort, spiritual care, access to care and resources,
      communication, support for parental decision making, and caring/ humanism.
      CONCLUSION: There are clear dimensions of pediatric EOL care that are important
      to parents; these can be defined in terms of health care provider behaviours,
      some of which require balancing seemingly conflicting objectives. Developing a
      measurement tool based on these dimensions would help to improve the quality of
      pediatric EOL care.

PMID- 22372283
TI  - Can addressing death anxiety reduce health care workers' burnout and improve
      patient care?
AB  - Death anxiety may interfere with health care workers' (HCWs) relationships with
      patients and patients' families and increase HCWs' levels of burnout. This study
      shows the impact of a six-day course for HCWs that provided training in
      communication, in offering emotional and spiritual support to patients, and in
      personal introspection on death anxiety. The HCWs were given questionnaires to
      evaluate their level of burnout, personal well-being, and death anxiety as well
      as the quality of their relationships with patients before the course and four
      months after it. There were 150 study participants, all HCWs involved in caring
      for dying patients (85 in palliative care units and 65 in other settings). There
      was a control group of 26 HCWs who cared for the dying in settings other than
      palliative care units. The results show that the course appeared to lead to a
      significant reduction in levels of burnout and death anxiety; they also indicated
      an increase in personal well-being and professional fulfillment, and participants
      perceived an improvement in the quality of their relationships with patients and
      patients' families.

PMID- 22372284
TI  - Palliative cancer patients' experience of physical activity.
AB  - Results from pilot studies indicate that palliative cancer patients report
      increased well-being and less fatigue after physical activity. This study aimed
      to explore how palliative cancer patients experienced physical activity. A
      qualitative design with semi-structured interviews was used. Eleven palliative
      cancer patients over 18 years old with different diagnoses and Eastern
      Cooperative Oncology Group Scale performance status levels of between 1 and 3
      were interviewed. Four main themes emerged: routines of everyday life, less
      fatigue, professional guidance, and hope. The first theme comprised two
      categories: something to do, and being together with others in a similar
      situation. The theme professional guidance also comprised two categories: the
      physiotherapist as tutor, and the physiotherapist as motivator. Some cancer
      patients in palliative care who participated in physical activity experienced
      less fatigue and enhanced energy. Physical activity helps to bring structure to
      everyday life and gives a feeling of hope for the future.

PMID- 22372285
TI  - Medical officers in acute care settings: their views on medically assisted
      hydration at the end of life.
AB  - This study explored the perceptions of doctors in acute care settings regarding
      the use of medically assisted hydration (MAH) in end-of-life care. The use of MAH
      at the end of life is controversial, and practice varies across health care
      settings. A qualitative study using discourse analysis was carried out. Eight
      medical practitioners in the acute care setting were interviewed individually.
      MAH has been associated with care, comfort, and standard medical intervention to
      save lives. Medical officers have some concerns about the benefits or adverse
      effects of MAH at the end of life. In acute care settings, it can be difficult to
      recognize and diagnose dying. Often, family discussions regarding end-of-life
      care do not occur due to pursuit of cure and, therefore, continuation of futile
      and burdensome treatment such as MAH can occur in the last few days of life.

PMID- 22372286
TI  - Creating new worlds: the importance of narrative in palliative care.

PMID- 22372287
TI  - Katherine Arbuckle and Melinda Hancock; a clinical transformation journey.

PMID- 22372288
TI  - Preparing for health insurance exchanges.

PMID- 22372289
TI  - 5 ways to engage physicians in financial decision making.

PMID- 22372290
TI  - FASB's ASU 2011-7 changes financial statement reporting requirements.
AB  - FASB's new Accounting Standards Update 2011-07 will change how healthcare
      entities accumulate and report major portions of their financial statements,
      including patient revenues, net accounts receivables, and bad-debt expenses.
      Healthcare entities now must reclassify their provisions for bad debts associated
      with patient service revenue from an operating expense to a deduction from
      patient service revenue (net of contractual allowances and discounts).
      International Financial Reporting Standards do not require healthcare entities to
      comply with this new standard.

PMID- 22372291
TI  - Using technology to reveal true costs.
AB  - Healthcare leaders should address three important questions as they prepare to
      implement new costing systems: Do all providers in their organizations' systems,
      networks, or partnerships share the same definitions of unit of care and of
      fixed, variable, incremental, direct, and indirect costs? What are the
      maintenance processes and protocols for cost center and period matching of
      revenues and costs? If some providers within a network or partnership are not
      using costing systems, can an enterprise derive surrogate cost per unit of care?

PMID- 22372292
TI  - Don't lose money with your technology upgrade.
AB  - Hospitals nationwide have seen revenue drop after implementing new financial and
      clinical IT platforms, typically because their adoption teams did not plan for
      the impact on downstream revenue. Technology is rarely a panacea. Although an
      upgrade can catch some problems, it can also add a new level of complexity that
      will make it harder to fix poor processes if they are not addressed up front.
      Finance departments should be involved in design and testing phases of all IT
      system changes--even nonfinancial systems--to protect revenues before, during,
      and after implementation.

PMID- 22372293
TI  - Do EHR investments lead to lower staffing levels?
AB  - A study used FTE employees per adjusted occupied bed (FTE/AOB) as a measure to
      ascertain the effect of EHR investments on labor productivity. The study focused
      on three primary questions: Do FTE/AOB decline as the number of EHR applications
      used in a hospital increases? Is impact on FTE/AOB greater with some EHR
      applications than with others? Do FTE/AOB decline overtime, as the hospital
      continues to use the EHR application?

PMID- 22372294
TI  - Dynamic CDM strategies in an EHR environment.
AB  - A dynamic charge description master (CDM) integrates information from clinical
      ancillary systems into the charge-capture process, so an organization can reduce
      its reliance on the patient accounting system as the sole source of billing
      information. By leveraging the information from electronic ancillary systems,
      providers can eliminate the need for paper charge-capture forms and see increased
      accuracy and efficiency in the maintenance of billing information. Before
      embarking on a dynamic CDM strategy, organizations should first determine their
      goals for implementing an EHR system, include revenue cycle leaders on the EHR
      implementation team, and carefully weigh the pros and cons of CDM design
      decisions.

PMID- 22372295
TI  - Developing capabilities for real-time capacity management.
AB  - A key healthcare reform strategy for hospital executives this year will be
      determining how capacity management can improve overall performance. Real-time
      data can give a hospital the kind of business intelligence it needs to make the
      most of what it has, act as an early warning system for problems, and provide the
      hospital with the tools to make long-term improvements. True enterprise
      management systems promise to deliver bottom-line impact that may be greater and
      more immediate than the conversion to electronic medical records.

PMID- 22372296
TI  - Storing radiology images in the reform era: what CFOs need to know.
AB  - Vendor-neutral archives (VNAs) normalize PACS images and make image exchange
      possible, even when multiple divergent PACS or radiology departments are
      involved. These systems, onsite or cloud-based, allow for strategic and long-term
      growth regardless of the PACS used. Radiologists continue to operate with their
      system/vendor of choice, further strengthening productivity, satisfaction, and
      organizational loyalty. Finance executives shave costs, avoid future PACS
      expenses, and gain greater leverage with PACS vendors.

PMID- 22372297
TI  - ICD-10: from assessment to remediation to strategic opportunity.
AB  - Healthcare finance teams should perform an enterprisewide assessment to determine
      what ICD-10 means to their organization, strategically, operationally, and
      financially. CFOs should strategically evaluate the impact of ICD-10 on the
      organization's entire financial operation. Organizations should have a
      contingency plan in place across all processes.

PMID- 22372298
TI  - Medicare incentive payments for meaningful use of electronic health records:
      accounting and reporting developments.
AB  - The Healthcare Financial Management Association through its Principles and
      Practices (P&P) Board publishes issue analyses to provide short-term practical
      assistance on emerging issues in healthcare financial management. In a new issue
      analysis excerpted in this article, HFMA's P&P Board provides some clarity to the
      healthcare industry on certain accounting and reporting issues resulting from
      incentive payments under the Medicare program for the meaningful use of
      electronic health record (EHR) technology. Consultation on these matters with
      independent auditors is highly recommended.

PMID- 22372299
TI  - Shutting the door on avoidable hospital readmissions.

PMID- 22372300
TI  - Physician champions drive value--but how do you find them?

PMID- 22372301
TI  - What would you do? Which system is the best target for a close affiliation?

PMID- 22372302
TI  - A look back in time.

PMID- 22372303
TI  - Handling confusion regarding electronic health records and HIPAA-governed breach
      of patient information.

PMID- 22372304
TI  - Self-estimated oral and general health are related and associated with clinically
      investigated dental health.
AB  - The aim was to investigate whether the self-estimation of oral and general health
      is correlated and related to clinical parameters for dental health. Furthermore,
      to investigate the influence of socioeconomic factors on the self-assessment of
      oral and general health. During 2007 a dental health survey was performed in the
      Community of Gavle located in central Sweden. 1, 224 subjects randomized from the
      general population of Gavle (adult population 75, 000) were invited to
      participate. Seven hundred and forty-eight individuals answered a questionnaire
      regarding their health and 373 of these subjects participated in a dental
      examination. Self-estimated oral and general health was correlated (p<0.0001,
      r=0.35) and individuals who perceived their oral health as bad had more decayed
      surfaces, surfaces with secondary caries, fewer teeth and more bleeding on
      probing than those with good estimated oral health (p<0.017 for all). In a
      logistic regression analysis with self-estimated oral health as the dependent
      variable was related to, the independent variables NT, DFT, self-estimated
      general health and age were related to self-estimated oral health, but not to
      income or educational level. However, subjects with low disposable income and low
      education level had significantly more clinical caries and fewer teeth than
      subjects with high income or a high educational level. CONCLUSIONS: In the
      present study, self-estimation of oral and general health was correlated and
      related to some clinical oral parameters. Subjects in the low socioeconomic group
      had worse dental health and a tendency to underestimate their need of dental
      care.

PMID- 22372305
TI  - Cellular responses to cobalt-chrome and CP titanium--an in vitro comparison of
      frameworks for implant-retained oral prostheses.
AB  - The responses of cell types in peri-implant tissues to cobalt-chrome and titanium
      were studied in vitro. Cylinders were made from both a cobalt-chrome alloy and
      commercially pure titanium (length 6 mm, diameter 7.9 mm). Plastic tubes were
      placed over the cylinders to create cell culture wells, in which human epithelial
      cells or mouse fibroblasts were cultivated. Cell viability was studied using the
      Alamar Blue method. The surface structure of two samples of each material was
      analyzed with optical interferometry. The morphology of cells grown on cylinders
      of each material was studied with scanning electronic microscopy. Epithelial
      cells and fibroblasts in the titanium group were more viable than those in the
      cobalt-chrome group (p = 0.001 and p = 0.000, respectively). The titanium
      surfaces had a greater height deviation (S(a), p = 0.027) but were less dense
      (S(ds), p = 0.044) than the cobalt-chrome group. The scanning electronic
      microscopy revealed no major deviations from normal cell morphology. Within the
      limitations of the present study, the findings indicate that epithelial cells as
      well as fibroblasts have a stronger negative response to cobalt-chrome alloy than
      to titanium. We suggest that these differences can be explained only bythe
      material per se and not by the minor differences in surface structure. Further
      and clinical studies are needed to confirm the significance of these findings.

PMID- 22372306
TI  - Sleeping position and reported quality of sleep. A comparison between subjects
      demanding treatment for temporomandibular disorders and controls.
AB  - The aims of the present study were to investigate if there are differences
      concerning preferred body posture during sleep between 100 patients, 66 women and
      34 men, mean age: 49 years (range: 20-85 years) referred to a specialist clinic
      because of TMD and 100 matched controls from a public dental clinic. The
      participants were asked to answer a questionnaire with questions about TMD
      symptoms and neck or shoulder pain. They were also asked about preferred sleeping
      position as well as about perceived sleep quality. No differences could be found
      between the two groups in respect of sleeping position. However, significantly
      more individuals in the TMD group compared to the controls had changed their
      preferred sleeping position due to their face and/or jaw and/ or neck-shoulder
      symptoms. Subjects in the TMD group also more frequently stated that they often
      felt insufficiently rested at awakening and/or felt tired or sleepy in the
      daytime because of symptoms from face/jaws. A significant number in the control
      group reported TMD symptoms indicating a latent need for TMD treatment. It is
      concluded that sleep position seems to have little or no significance for the
      development or maintenance of TMD symptoms. However, the study indicates that TMD
      symptoms and associated neck- and shoulder pain affect the quality of sleep.

PMID- 22372307
TI  - Dental agenesis patterns in Crouzon syndrome.
AB  - Dental agenesis may be present in an isolated familiar manner, or occur as a part
      of a syndrome.To date, this clinical trait seems to have been overlooked in
      patients with Crouzon syndrome.The aim of the present study was to investigate
      dental agenesis and dental agenesis patterns in a population of persons with
      Crouzon syndrome in Sweden. Serial panoramic radiographs of 26 individuals with
      Crouzon syndrome (20 males, 6 females) were examined.Third molars were excluded
      from the assessment. The prevalence of agenesis for at least one tooth was 42.3%.
      Each affected patient was found to have up to 5 missing teeth. Upper and lower
      second premolars were the most frequently congenitally missing teeth. Eleven
      dental agenesis patterns of the entire dentition were identified, as described by
      the tooth agenesis code (TAC). All patterns were unique and asymmetric,with only
      one exception, a symmetric pattern of the maxillary and mandibular second
      premolars. In conclusion, persons with Crouzon syndrome were found to have a high
      prevalence of dental agenesis and a remarkable variability of dental agenesis
      patterns. It is important to be aware of this clinical situation, especially when
      orthodontic treatment planning for these patients is performed as early as in the
      mixed dentition.

PMID- 22372308
TI  - Fluoride toothpaste and toothbrushing; knowledge, attitudes and behaviour among
      Swedish adolescents and adults.
AB  - The most effective way to administer fluoride is through the regular use of
      fluoride toothpaste. Adolescents and adults seem to have low awareness of
      toothbrushing procedures and use of fluoride toothpaste despite frequent dental
      care. The aim of this study was to describe knowledge, attitudes and behaviour
      concerning toothbrushing and use of fluoride toothpaste in three age groups in a
      Swedish population. A qualitative study design was used with the purpose of
      achieving a deeper understanding of the issue. Data were collected through
      interviews. A manifest and latent analysis of the text was performed using
      qualitative content analysis (Grounded theory). The informants were selected
      strategically to obtain the greatest possible variation in the data. Three age
      strata representing different stages in life were chosen: 15-16, 30-35 and 60-65
      years. Informants were interviewed with support from an interview guide. Open
      ended questions were used to focus on the individual's knowledge, attitudes and
      behaviour concerning toothbrushing and fluoride toothpaste. Five people from each
      age group were interviewed in the study. The content areas were knowledge,
      attitudes and behaviour and the latent analysis identified the areas of
      empowerment, driving force and guidance as categories. Although the informants
      showed little knowledge about the reasons for and techniques of using fluoride
      toothpaste effectively, they described toothbrushing as important and the habit
      as a priority, giving the theme of this study: toothbrushing with fluoride
      toothpaste was a priority, despite the lack of knowledge about how to use
      toothpaste effectively and its positive effects on oral health. In conclusion the
      state of knowledge concerning toothbrushing and fluoride toothpaste needs to be
      improved. In addition, people's desire for a fresh-feeling mouth and to fit in
      socially must be affirmed and utilized by dental staff in health promotion.

PMID- 22372309
TI  - Building knowledge capital.
AB  - Formal, ongoing board education ensurestrustees are able to make informed
      decisions.

PMID- 22372310
TI  - Location, location, location.
AB  - Rural hospitals rethink their strategies for recruiting physicians, including
      offering unique incentives.

PMID- 22372311
TI  - Smart money management.
AB  - Facing reduced reimbursement and climbing costs, hospitals are experimenting with
      ways to cut expenses.

PMID- 22372312
TI  - Governing large nonprofit systems: a preview of CEO, trustee perspectives.

PMID- 22372313
TI  - 10 trends for 2012.
AB  - Although uncertainty around reform continues, hospitals can plan on these
      influential trends.

PMID- 22372314
TI  - Putting patients first. Interview by Matthew Weinstock.
AB  - Benjamin Chu, M.D., sees system change from the patient's perspective.

PMID- 22372315
TI  - Building bench strength.
AB  - Reform changes the way boards and executives look at leadership development and
      succession planning.

PMID- 22372316
TI  - A road to better governance.
AB  - An elected board uses competency-based peer assessment to improve governance and
      outreach.

PMID- 22372317
TI  - [Development, aims and status quo of the EU animal disease law].
AB  - The development of EC legislation is outlined using swine fever and foot and
      mouth disease as an example, starting with the possibility of vaccinating against
      both animal diseases in the 1980s without substantially restricting trade with
      vaccinated animals or products of these animals, right up to a policy of non
      vaccination with the realisation of the single market with significant
      restrictions on intra-Community trade if the option of an emergency vaccination
      were to be used.The restrictions associated with emergency vaccination are
      basically tantamount to a vaccination ban. To that extent, vaccination needs to
      be taken into consideration as an instrument of animal disease control under the
      EU animal health legislation currently being discussed, the aim being for
      vaccinated animals that have tested as virus-free to be able to be marketed
      without any restrictions. This will, however, only be possible if all
      stakeholders (EU, member states, World Organisation for Animal Health, industry,
      consumers) achieve a broad consensus.

PMID- 22372318
TI  - [Acceptance of alternative disease control strategies in the European Union].
AB  - The European Commission intends to change its animal disease control strategy
      following the slogan "Prevention is better than cure". Vaccination and
      diagnostics should play a major role in emergency situations. A policy paper
      regarding the use of vaccines has been discussed with all Member States and the
      main aspects were evaluated in a questionnaire. In principle, the majority of
      Member States are in favour of a future strategy in which vaccination is
      replacing culling. However, questions regarding the pathogen freedom and the
      trade of vaccinated animals and animal products from vaccinated animals still
      remain open.

PMID- 22372319
TI  - [Innovations in the diagnosis of infectious agents of veterinary importance--a
      seven-league boots fairy tale?].
AB  - The development of infectiological diagnostic methodology is characterized by
      saltatoric, revolutionary leaps. Improved sensitivity and specificity, reduction
      of analytical sample volumes, increased sample throughput, reduced test
      complexity associated with improved user friendliness are hallmarks of such
      developments. Apart from purely technical amenities some innovations also enable
      conceptual adaptations of monitoring strategies. These include the use of
      diagnostic assays on-site, e. g. in the stable or in the practice. Selecting the
      assay which is most "fit-for-purpose" among the plethora of sometimes loudly
      advertised new technology may be difficult even for the well trained and
      experienced diagnostician. Standardized licensing procedures for infectiological
      diagnostic kits may be required to guarantee minimal norms of diagnostic quality.
      At the same time availability of a diversity of diagnostic kits is needed to
      broaden the base of diagnostic reliability. New infectiological diagnostic
      innovations will only be useful if the (expanded) results are transposable to the
      improved practical care of companion animals and farm animal holdings. In
      addition, the judgment of results, e. g. for epidemiological plausibility,
      remains a very important issue even when the test results have been produced by
      novel high technology diagnostics.

PMID- 22372320
TI  - Classical swine fever and avian influenza epidemics: lessons learned.
AB  - Experience with recent large-scale epidemics of Classical Swine Fever and Avian
      Influenza--among others in the Netherlands--have teached us several lessons that
      should prepare us better for future outbreaks. Among others, improving early
      detection of outbreaks--by using syndrome surveillance systems--is a key factor,
      in which farmers and veterinary practitioners have an imminent role. A major step
      in this respect is facilitation of the use of exclusion diagnostics without
      closing down the farm in clinical situations with non-specific clinical signs
      observed in sick animals. The hesitance of farmers and veterinary practitioners
      to report a suspect clinical situation on a livestock farm and how to facilitate
      that process is another major issue. Furthermore, the importance of communication
      between the field and the laboratory with respect to post mortem examination will
      be highlighted, and the need for outbreak simulation exercises with neighbouring
      countries in order to be better prepared, will be discussed.

PMID- 22372321
TI  - [Morphological studies in different avian species on artefacts induced by
      euthanasia with T 61 " or Pentobarbital (Narcoren)].
AB  - In mammals (e. g. macaques, dogs, cats, rats, sheep) as well as in men (suicides)
      euthanasia performed by intravenous injection of T 61 leads to serious lesions in
      lung, kidney or/and liver (endothelial damage, hyperemia, oedema, necrosis). This
      is caused by the solvent dimethylformamide (DMF). In this study, in contrast, in
      different species of birds (e. g. blackbird, carrion crow, kestrel, common
      buzzard, homer pigeon, common wood pigeon, mallard duck) and various modes of
      applications and dosages T 61, 1.0-3.0 ml/kg body mass, did not induce comparable
      artefacts in tissues of internal organs in the narcotized animals.
      Microscopically, only hyperemia and oedema of lung, kidney and/or liver were
      found. However, milder but similar lesions were detected also in groups of birds
      euthanized by pentobarbital (200 mg/kg body mass) as well as in control groups
      (overdosed ketamine intramusculary, 100 mg/kg body mass, and rapid
      exsanguination). In conclusion, euthanasia of narcotized birds performed by
      intravenous or intracardial injections ofT 61 seemed to be suitable. The observed
      lesions could therefore not be interpreted as T61 induced artefacts.

PMID- 22372322
TI  - Identification of Arcanobacterium (Trueperella) abortisuis, a novel species of
      veterinary importance, by matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF MS).
AB  - In the present study A. (T.) abortisuis isolated from pigs and bovines could be
      reliably identified by determination of phenotypic properties, genotypically by
      polymerase chain reaction with the help of A. (T.) abortisuis 16s-23S rDNA
      intergenic spacer region specific oligonucleotide primer and by Matrix-Assisted
      Laser Desorption Ionization-Time Of Flight mass spectrometry (MALDI-TOF MS). The
      latter appeared to be a promising tool for fast and cost effective identification
      of this species and might help to elucidate the role A. (T.) abortisuis plays in
      infections of pigs, bovines, possibly other animals or humans.

PMID- 22372323
TI  - [Paratuberculosis in a miniature donkey (Equus asinus f. asinus)].
AB  - Paratuberculosis is mainly an infectious disease of ruminants with worldwide
      distribution. Infection occurs in early stages of life. Other animal species
      beyond ruminants are rarely affected, however, experimental and natural
      infections are possible. A case of paratuberculosis in a miniature donkey (Equus
      asinus f. asinus) with typical clinical and pathomorphological changes is
      reported here. Lesions were mainly observed in the intestine. Causative for the
      profuse diarrhoea with emaciation was massive diffuse granulomatous enteritis
      involving large quantities of acid-fast organism mainly in macrophages.
      Granulomatous inflammation with acid-fast bacilli again in macrophages to a
      lesser degree could be detected in the liver. Mycobacterium avium subsp.
      paratuberculosis (MAP) was isolated from intestinal contents after an incubation
      period of four weeks. MAP-specific DNA (IS900 and f57) was detected by polymerase
      chain reaction in culture material. Additionally MAP-isolates were characterized
      by multi-target genotyping (MIRU-VNTR- and MLSSR-typing). Isolates belonged to
      the Type II group and exhibited a unique genotype different from other MAP
      strains in Germany. The donkey originated from a donkey breeding farm in France
      with intensive free ranging cattle in the neighbourhood and could have been
      infected there. Donkeys should be considered as paratuberculosis-susceptible
      animals in exceptional cases and as possible reservoirs or disseminators of
      infection.

PMID- 22372324
TI  - Electrolyte level and blood pH in dogs infected by various 18S RNA strains of
      Babaesia canis canis on the early stage of babesiosis.
AB  - The purpose of the studies was to determine electrolyte disturbances and blood pH
      changes in dogs with babesiosis and possibly show a connection between the
      Babesia (B.) canis strain causing the infection and the intensity of these
      irregularities. 40 animals (group 1) with early babesiosis and 40 healthy dogs
      (group 2) were studied and their blood pH and blood levels of potassium,
      chlorides; calcium and sodium were determined. At the same time, molecular typing
      of parasites was carried out to detect which B.canis strain (18S RNA-A or 185 RNA
      B) had caused the disease in dogs of group 1. In group 1, four dogs were
      acidaemic, twelve had normal blood pH, and 24 were alkalaemic. Potassium
      concentration was below normal in 16 out of 40 dogs (40%) and normal in 24 dogs.
      Hypochloremia was present in 36 out of 40 dogs; chloride was normal in the
      remaining four animals. Serum sodium concentration was low in 16 of 40 dogs,
      normal in 20 of 40 dogs and high in four dogs. Calcium concentration was normal
      in all 40 dogs. In dogs of group 2 no abnormalities of haematological or blood
      biochemical parameters were observed. 29 out of the 40 dogs of group 1 were
      infected with the 18S RNA-A strain and eleven with the 18S RNA-B strain of
      Babesia canis canis. We did not observe any correlation between the type of
      strain causing the infection and the electrolyte disturbances in the serum of
      sick dogs. Hypocalaemia was observed in ten specimen infected with 18S RNA-A and
      six infected with 18S RNA-B. Additionally, in dogs infected with 18S RNA-A,
      hypochloraemia (28), hyponatraemia (10), hypernatraemia (2) were observed, as
      well as blood pH drop (4) or increase (14). The 18S RNA-B-infected dogs suffered
      from hypochloraemia (8), hyponatraemia (6), hypernatraemia (2) and increase in
      blood pH (10).The studies conducted did not answer the question of whether the
      type of electrolyte disturbances in dogs with babesiosis can be connected with
      the strain of the parasite that induced the disease, as happens in the case of
      other clinical parameters (Adaszek et al., 2009). Further studies in this
      respect, conducted on a larger group of animals, are necessary.

PMID- 22372325
TI  - [Regionalisation of Germany by data of agricultural structures].
AB  - In order to simplify the design of representative studies in animal populations
      the structural differences of animal husbandry (cattle, pigs and laying hens) in
      Germany were characterised. Several regions were defined and thus districts
      identified which are typical for the respective region and can be regarded as
      representatives for the whole region. Data on animal husbandry as well as human
      population per district originated from the Federal Statistical Office and were
      linked to the geometric data of the Federal Agency for Cartography and Geodesy.
      By this, data of "livestock units/square kilometre area" and "farms/square
      kilometre area" per district were calculated using methods of the spatial
      statistics Global Moran's Index, Anselin Local Moran's Index and Getis-Ord Gi*.
      With the help of these analyses six clusters could be identified which resulted
      in four large (Middle, Northwest, East, and South) and one smaller region
      (Northern Upper-Rhine) respecting the federal state borders. These regions
      differed significantly regarding animal and farm densities. The selection of
      typical districts was carried out with the help of the respective animal and farm
      data of the species pigs, dairy cattle and laying hens. The means of the selected
      districts (three to six per region) were within the 60%- and the 80%-percentile
      of at least two of the analysed variables. Concerning the region Northern Upper
      Rhine no representative district was selected. This presented regionalisation
      including representative districts can be used for the design of scientific
      studies that are associated with animal husbandry in Germany.

PMID- 22372326
TI  - [Detection of fowlpox in chickens and turkeys in Germany].
AB  - The present work outlines molecular diagnostic examinations for detection of
      poxvirus infection in chickens and turkeys in Germany over a time period of
      twelve years. Diagnostic samples suspected for fowlpox were investigated using
      the polymerase chain reaction (PCR) in combination with restriction enzyme
      analysis (REA) for presence of fowlpox virus (FPV) specific DNA. For a long
      period of time fowlpox did not play a role in commercial poultry farms in
      Germany. Beginning in 1999 an increasing number of new infections was identified.
      During the whole study period FPV specific DNA was detected in 92 out of 192
      investigated samples. Positive samples were derived especially from layer hens
      but also from broiler breeders, turkey breeders, and meat turkeys. Thereby, a
      differentiation between isolates of chickens and turkeys by restriction enzyme
      analysis (REA) was not possible. As possible explanations for this reemergence,
      especially the lack of prophylactic vaccination in the past as well as an
      increasing number of alternative rearing systems has to be considered. Beginning
      in 2003, a downward tendency was observed following intensification of
      prophylactic vaccination.

PMID- 22372327
TI  - Serological studies on Corynebacterium pseudotuberculosis infections in goats in
      Baden-Wuerttemberg (Germany) and seroreactions on antigens used for newly
      developed enzyme-linked immunosorbent assays (ELISA).
AB  - In the present study, comprehensive data on the seroprevalence of Corynebacterium
      (C.) pseudotuberculosis infections in goats are presented for Baden-Wuerttemberg,
      a Federal State of Germany, for the first time. As a prerequisite, ELISAs based
      on a recombinant phospholipase D (rPLD) and whole cell antigens (WCA) were
      designed and validated yielding sensitivity values of 81% and 97% and specificity
      values of 98% and 99%, respectively. Immunisation trials in goats demonstrated a
      significant production of antibodies to rPLD but an evidently lower antibody
      production to WCA as determined in the corresponding ELISA. Moreover,
      immunisation with rPLD resulted in the formation of antibodies, which were also
      detected in the WCA ELISA. In contrast, this phenomenon was not observed with the
      rPLD ELISA after immunisation with WCA. Implementation of the rPLD and WCA ELISAs
      in a broad-based seroprevalence study in Baden-Wuerttemberg revealed positive
      reactions in both ELISAs in 13.2% of the 1771 goat sera tested. In 53.7% of 121
      herds of which five or more animals were tested per herd there was at least one
      animal that showed a positive reaction in both tests.

PMID- 22372328
TI  - [Time trends and seasonal variation of iodine content in German cow's milk-
      investigations from Northrhine-Westfalia].
AB  - Cow's milk is one of the most important iodine providers in the human diet. The
      milk iodine content (MIC) is significantly determined by cattle feeding. The aim
      of the study was to investigate the longitudinal development of the MIC of German
      cow's milk during the last years and to assess the current contribution of milk
      consumption to the population's iodine supply. MIC was analysed by a Cer-Arsenit
      method after alkaline wet washing in 112 milk samples from nationwide available
      trademarks (eight samples each were purchased in June and December from 2004
      onward to 2010 in the same food markets in the greater Dortmund area). We found
      an increasing trend of MIC until 2010 (p < 0.005).The mean MIC in 2004/05 was 97
      +/- 32 microg/I, in 2009/10 it was 110 +/- 36 microg/l. This increase was only
      observable for conventionally (p = 0.0003), and not for organically produced milk
      (p = 0.6). The MIC of summer milk was about 22 microg/l lower than that of winter
      milk (p < 0.0001), however, seasonal variation was especially pronounced in
      organically produced milk. MIC of organically produced milk was in average about
      54 microg/l lower than that of conventionally produced milk (p < 0.0001). Thus,
      the moderate increase of MIC to 110 microg/l on average contributes to the
      maintainence of the population's iodine supply, whereas the analysed maximum
      iodine contents of around 160 microg/l do not give reason to expect an excessive
      iodine intake, even in case of a high milk consumption. An appropriate iodine
      supplementation in foodstuff can be assumed.

PMID- 22372329
TI  - Learning and memory-enhancing effect of Bacopa monniera in neonatal rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the learning and memory
      enhancing effect of Bacopa monniera in neonatal rats. BACKGROUND: Learning is an
      acquisition and storage of information as a consequence of experience. Memory is
      a relatively permanent storage form of the learned information. In the process of
      'learning', activation of neurons occurs in specific areas or specific memory
      systems of the brain concerned with the processing of the specific modality of
      sensory information. Rasayana plants are said to prevent ageing, re-establish
      youth, strengthen life, brain power and prevent diseases. Bacopa monniera (BM) is
      shown to be very useful in improving learning and memory. METHODS: In the present
      study neonatal rat pups (10 days old) were given different doses of BM extract
      orally for different periods of time. These rats were then subjected to spatial
      learning (T- Maze) and passive avoidance tests along with the age matched normal
      and gum acacia control rats. The data were compared with those of control rats.
      RESULTS: The results showed improvement in spatial learning performance and
      enhanced memory retention in neonatal rats treated with extract of BM.
      CONCLUSION: We conclude that treatment with BM extract during growth spurt period
      of neonatal rats enhances learning and memory (Tab. 3, Fig. 3, Ref. 45). Full
      Text in free PDF www.bmj.sk.

PMID- 22372330
TI  - Antitussive activity of Althaea officinalis L. polysaccharide rhamnogalacturonan
      and its changes in guinea pigs with ovalbumine-induced airways inflammation.
AB  - AIM: The presented studies were aimed on experimental confirmation of Althaea
      officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes
      in conditions of allergic inflammation. METHODS: We have tested whether
      rhamnogalacturonan inhibits cough reflex and modulates airways reactivity of
      guinea pigs in vivo. The cough in guinea pigs was induced by 0.3 M citric acid
      (CA) aerosol for 3 min interval, in which total number of cough efforts (sudden
      enhancement of expiratory flow accompanied by cough movement and sound) was
      counted. Specific airway resistance and its changes induced by citric acid
      aerosol were considered as an indicator of the in vivo reactivity changes.
      RESULTS: 1) Althaea officinalis polysaccharide rhamnogalacturonan dose-
      dependently inhibits cough reflex in unsensitized guinea pigs. Simultaneously,
      plant polysaccharide shortened the duration of antitussive effect when it was
      been tested in inflammatory conditions. 2) Rhamnogalacturonan did not influence
      airways reactivity in vivo conditions expressed as specific resistance values
      neither sensitized nor unsensitized groups of animals. 3) The antitussive
      activity of codeine (dose 10 mg.kg(-1) b.w. orally) tested under the same
      condition was comparable to higher dose of rhamnogalacturonan in unsensitized
      animals. 4) The characteristic cellular pattern of allergic airways inflammation
      was confirmed by histopathological investigations. CONCLUSION: Rhamnogalacturonan
      isolated from Althaea officinalis mucilage possesses very high cough suppressive
      effect in guinea pigs test system, which is shortened in conditions of
      experimentally induced airways allergic inflammation (Tab. 1, Fig. 4, Ref. 25).
      Full Text in free PDF www.bmj.sk.

PMID- 22372331
TI  - The effect of ankaferd to stop bleeding in experimental partial nephrectomy.
AB  - AIMS: In kidney surgery, bleeding is one of the most important issues. In partial
      nephrectomy, as a "blood stopper", we used surgycell and ankaferd which is used
      traditionally in Turkish medicine. MATERIAL AND METHODS: 24 Wistar-Albino rats
      were grouped randomly. Laparotomy was performed in the first group, sham group.
      In the second group, partial nephrectomy was performed to lower-kidney pole and
      then, serum physiology was given to the lower part of the kidney. In the third
      group, partial nephrectomy was performed and surgycell was given over the kidney.
      In the fourth group, partial nephrectomy was performed and then ABS was applied.
      In all groups, the gauze was weighted on sensitive lift before and after the
      operation in order to determine the amount of bleeding. After the subjects were
      left alive for 5 hours, the levels of blood urea, and creatinine and kidney
      histopathology were evaluated. RESULTS: No meaningful difference between the
      groups was found as for the levels of blood urea, and creatinine and the kidney
      histopathology. Bleeding amount was diminished significantly in the group 4, to
      which ankaferd was applied. CONCLUSION: Ankaferd is a substance which can be used
      effectively for controlling acute bleeding in kidney surgery (Tab. 2, Ref. 19).
      Full Text in free PDF www.bmj.sk.

PMID- 22372332
TI  - The optimal timing for magnetic resonance imaging in long-term follow-up of
      patients after a complete correction of the Tetralogy of Fallot.
AB  - OBJECTIVES: Long-term pulmonary regurgitation (PR) leads to right ventricular
      (RV) dilatation and dysfunction. In patients after a complete correction of the
      tetralogy of Fallot (TOF) it represents the most frequent and high risk late
      complication. Magnetic resonance imaging (MRI) is an objective possibility for RV
      measurements; on the other hand MRI is complicated and not always accessible
      method. BACKGROUND: We analyzed echocardiography (ECHO) and MRI parameters
      regarding RV dilatation and function and the correlation between these two
      methods with the aim to define optimal ECHO parameters indicating a necessity for
      further investigations. PATIENTS AND METHODS: In 50 patients with TOF > 10 years,
      after a complete surgical correction, ECHO and MRI were performed. RESULTS: ECHO
      finding of end-diastolic diameter (EDD) of RV > 30mm was detected in 13 patients
      (26%) and in 30 patients (60%) RV EDD above 4 standard deviations (SD) their
      normal values was present. MRI finding of end-diastolic volume (EDV) > 160 ml/m2
      was present in 14 patients (28%) and end-systolic volume (ESV) > 85 ml/m2 in 17
      patients (34%). Significant correlations between ECHO and MRI RV diastolic
      measurements were found (p=0.0001, r=0.34, resp. p=0.001, r=0.39). PR was
      significantly affecting diastolic RV dilatation (p=0.0001), on the other hand. RV
      dysfunction resulted in systolic RV dilatation (p=0.007). PR did not correlate
      with RV function (p=0.56). CONCLUSIONS: MRI is a golden standard for exact RV
      measurements and for the indication of pulmonary valve replacement, but ECHO
      still can be used during long-term follow-up, defining the point for further and
      more exact RV measurements (Tab. 2, Fig. 11, Ref. 17). Full Text in free PDF
      www.bmj.sk.

PMID- 22372333
TI  - Study on possibilities of reconstructive--plastic surgery in patients with stage
      III breast cancer.
AB  - BACKGROUND: This population based study aimed to use reconstructive-plastic
      surgery with autologous tissue as a treatment of patients with stage III breast
      cancer. PATIENTS AND METHODS: We identified women (374) diagnosed with stage III
      breast cancer between 2000 and 2009 years. We compared radical operations with
      and without a plastic step, where 29 patients underwent the surgery in
      combination with an immediate radical resection with LD-flap replacement,
      mastectomy concurrently to TRAM-flap reconstruction in 103 patients. RESULTS: We
      examined the immediate and remote results of therapy. In data analysis, there
      were higher summarized indices of physical and mental health rates in patients
      who underwent the reconstruction plastic surgery compared to patients with
      mastectomy. All treated women 5 -year survival rate was 77.4+3.6 %, 63.5+3.2% and
      40.1+3.1 % in stages IIIa, IIIb, IIIc respectively. In the control group, the
      rates were 78.6+3.4 %, 64.0+3.3 %, and 39.3+3.1 % (p<0.05) respectively.
      CONCLUSION: Our results showed that women with stage III breast cancer who
      underwent reconstructive-plastic surgeries had a chance to improve their quality
      of life, and did not increase the frequency, neither did reduce 5 year survival
      (Tab. 2, Fig. 4, Ref. 19). Full Text in free PDF www.bmj.sk.

PMID- 22372334
TI  - Idiopathic intracranial hypertension: a retrospective clinical study.
AB  - BACKGROUND: Idiopathic intracranial hypertension is a disorder characterized by
      an increased intracranial pressure, without deformity and obstruction of the
      ventricular system. There is a predilection of occurrence in obese women of
      childbearing age. The pathogenesis of idiopathic intracranial hypertension is
      likely related to abnormalities in the balance between production and drainage of
      cerebrospinal fluid. Diagnosis is made by excluding the known causes of elevated
      intracranial pressure. OBJECTIVE: To evaluate the features, possible causes,
      treatment, and incidence of idiopathic intracranial hypertension as seen in
      patients attending our Department of Neurology. METHODS: We retrospectively
      analysed a group of patients diagnosed with idiopathic intracranial hypertension
      in our Department of Neurology during a twenty-year period (1989 to 2008).
      RESULTS: In six patients we confirmed the diagnosis of idiopathic intracranial
      hypertension during this period. Five of them were females and one was male, the
      average age of the patients was 32.30 years (22 to 52). The calculated incidence
      of idiopathic intracranial hypertension in our group was 0.15 per 100,000
      persons. Out of these six persons there were four cases diagnosed in the last
      five years, changing the calculated incidence to 0.4 per 100,000 persons in this
      period. The average body mass index in our patients was 26.33 kg/m2 (20.1 to
      31.38). CONCLUSION: We suppose that the increased incidence of idiopathic
      intracranial hypertension in our patients in the last five years has been
      associated with an advance in diagnostics. With literary data, half of our
      patients were obese or overweighted, but all of them underwent also hormonal
      treatment, some had iron deficiency and one of them was pregnant (Tab. 3, Fig. 1,
      Ref. 17). Full Text in free PDF www.bmj.sk.

PMID- 22372335
TI  - From preoperative to intraoperative detection of hyperfunctioning parathyroid
      glands using tetrofosmin (99mTc) in primary hyperparathyroidism.
AB  - The impact of preoperative scintigraphy on the management of patients with
      primary hyperparathyroidism has been largely documented for more than two
      decades. More recently, preoperative scintigraphy has also been used to select
      patients for intraoperative detection of hyperfunctioning parathyroid glands
      thanks to a gamma-probe. This procedure is now widely used, with MIBI as the main
      radiopharmaceutical for both preoperative scintigraphy and intraoperative
      detection. However MIBI was not available in Slovakia until very recently and
      tetrofosmin (TF), the alternative 99mTc labelled radiopharmaceutical for
      myocardial imaging has some advantages over MIBI and a close biological
      behaviour. Thus we have been using TF also for parathyroid preoperative
      scintigraphy and for intraoperative detection, a systematic indication which has
      never been reported by others. This article aims to demonstrate the feasibility
      and to present our protocol for TF parathyroid imaging and intraoperative
      detection, closely associating surgeons, nuclear medicine specialists,
      pathologists and also biologists as intraoperative assay of intact PTH is
      necessary. The results of literature are subsequently reported and discussed
      (Tab. 2, Fig. 4, Ref. 35). Full Text in free PDF www.bmj.sk.

PMID- 22372336
TI  - Gain in visual acuity after cataract surgery improves postural stability and
      mobility.
AB  - OBJECTIVES: Vision plays an important role in postural stability. It has also
      been shown that visual information from the environment and visual cues
      significantly contribute to balance skills. The aim of this study was to
      investigate the effects of visual acuity on postural stability and mobility
      before and after cataract surgery. METHODS: The study group was composed of 25
      male and 11 female patients (age 57-84, mean 66.6 +/- 4.7) who had been operated
      for age-related cataract. Postural stability and mobility were assessed before
      and four weeks after the surgery by means of Biodex stability system (BSS),
      Tinetti, Time up and go (TUG) and Functional reach (FR) tests, as well as by gait
      analysis (gait velocity, step length, step width, cadence, stride length).
      RESULTS: Postoperative visual acuity was significantly improved. Gait velocity
      and cadence increased significantly but step length, stride length, and step
      width did not change significantly. Postoperative improvement of Tinetti balance,
      TUG and FR tests were significant. Similarly, antero-posterior stability index
      (APSI), mediolateral stability index (MLSI) and overall stability index (OSI)
      that were examined with BSS improved significantly after the cataract surgery.
      CONCLUSION: These results demonstrated that gain in visual acuity after cataract
      surgery improves the postural stability and mobility of patients (Tab. 2, Fig. 1,
      Ref. 29). Full Text in free PDF www.bmj.sk.

PMID- 22372337
TI  - Upper gastrointestinal system hemorrhage in the emergency department.
AB  - OBJECTIVE: In the present study, we aimed to investigate demographic and clinical
      characteristics of the cases presented to the Emergency Department with an acute
      upper gastrointestinal system hemorrhage, and to identify the initial evaluation
      and treatments along with explaining possible causes of hemorrhage. MATERIALS AND
      METHODS: This prospective study was conducted between October 1, 2006 and
      September 30, 2007. Characteristics of the patients were evaluated in terms of
      age, gender, presenting symptoms, medical history, risk factors, coexisting
      symptom and diseases, results of the rectal examination and nasogastric
      evaluation, endoscopy findings, received treatments, duration of Emergency
      Department stay, admitting departments, and outcomes. RESULTS: 128 patients who
      presented to the Emergency Department during the study period were included in
      the study. As 27.3 % of the patients were female, 72.7 % were male. The mean age
      was 59.3 (+/- 16). 51.6 % of patients had a history of NSAID and aspirin use.
      Endoscopy was performed in 111 (86.7 %) patients. The most common finding among
      endoscopy results was gastric ulcer with a rate of 20.4 % followed by duodenal
      ulcer in 18.3 %. The mean hospitalization period in the Emergency Department was
      found to be 18 hours. CONCLUSION: In conclusion, acute upper gastrointestinal
      hemorrhages are first evaluated and treated in Emergency Departments. Endoscopy
      was carried out on most of the patients during the monitoring in the Emergency
      Department. NSAIDs and aspirin are still the most important risk factors and
      peptic ulcer is the most frequently encountered underlying cause (Tab. 4, Fig. 1,
      Ref. 27). Full Text in free PDF www.bmj.sk.

PMID- 22372338
TI  - What is the relationship between type 2 diabetes mellitus and urolithiasis?
AB  - AIM: Despite the high incidence of urolithiasis in general population, the exact
      underlying pathology is unknown. Possible association between urolithiasis and
      parameters of physical health were assesed in the presented study. MATERIAL AND
      METHODS: The study was performed at an Internal Medicine out patient unit during
      routine check ups. Patients between the ages of 20 and 70 years were studied to
      prevent debility induced weight loss in elderly. Patients with devastating
      illnesses were excluded to avoid their possible effects on weight. Cases with
      urolithiasis were collected in one group, and age and sex-matched cases without
      urolithiasis were collected in other group. RESULTS: Eighty cases with
      urolithiasis and 120 cases without were studied. Mean age of urolithiasis cases
      was 49.0 years, and 52.5 % of them were female. Mean weight of the urolithiasis
      cases was 76.0 kg, whereas it was 80.8 kg in the group without urolithiasis
      (p=0.013). The prevalence of type 2 diabetes mellitus (DM) was significantly
      higher in the urolithiasis group with unknown reasons (17.5 % vs 7.5 %, p<0.01).
      There was no significant difference as for the height, body mass index,
      prevalence of hypertension, and mean values of low density lipoprotein
      cholesterol, high density lipoprotein cholesterol, and triglyceride between the
      groups. CONCLUSION: In spite of several terrible effects of excess weight on
      health, we could not detect any association with urolithiasis, but there is a
      highly significant association between urolithiasis and type 2 DM, and it may
      have hundreds of mechanisms with variable priorities, which must be explained
      with further studies (Tab. 1, Ref. 21). Full Text in free PDF www.bmj.sk.

PMID- 22372339
TI  - Malignant hemophtalmus as a first sign of orbital rhabdomyosarcoma in adult.
AB  - We report on a rare case of an adult patient with rhabdomyosarcoma treated at the
      Dpt Ophthalmology, Comenius University, Medical School in Bratislava as a single
      case since 1968 (Fig. 2, Ref. 5). Full Text in free PDF www.bmj.sk.

PMID- 22372340
TI  - Pooled platelet concentrates and the quality of the red blood cell supply.

PMID- 22372341
TI  - Evaluation of calcium, magnesium, potassium, and sodium in biological samples
      (scalp hair, serum, blood, and urine) of Pakistani referents and arthritis
      patients of different age groups.
AB  - BACKGROUND: Rheumatoid Arthritis is a chronic inflammatory disease resulting in
      joint inflammation (particularly joints of hands, wrists, feet, knees, ankles,
      and shoulder) that is manifested by swelling and functional impairment. METHODS:
      This study was designed to compare the levels of calcium (Ca), magnesium (mg),
      potassium (K), and sodium (Na) in four biological samples (scalp hair, serum,
      blood, and urine) of patients with rheumatoid arthritis (RA) as compared to
      referent subjects of both genders who do have not arthritis problems. All
      patients and referents were divided in two age groups, (46-60) and (61-75) years.
      A microwave assisted wet acid digestion procedure was used for acid digestion of
      biological samples. The digests of all biological samples were analysed for Ca,
      Mg, K, and Na by flame atomic absorption spectrometry (FAAS). The proposed method
      was validated by using conventional wet digestion of the same sub samples and
      certified reference samples of hair, serum, blood, and urine. RESULTS: The
      results indicated significantly lower levels of Ca, Mg, and K in the biological
      samples (blood, serum, and scalp hair) of male and female rheumatoid arthritis
      patients when compared to referents of both genders, whereas the levels of Na
      were found to be high in blood and urine samples of patients as compared to
      nonrheumatic referents. CONCLUSIONS: These data represent a guide for clinicians
      and other professionals who will be investigating the deficiency of essential
      micronutrients in biological samples (scalp hair, serum, and blood) of rheumatoid
      arthritis patients.

PMID- 22372342
TI  - Objective identification of sexual risk behavior among blood donors in Croatia:
      is it reality?
AB  - BACKGROUND: The objective of this study is to determine the prevalence of blood
      donors positive for herpes simplex virus type 2 (HSV-2), to identify the patterns
      of sexual risk behavior responsible for HSV-2 positivity and to assess the
      reliability of HSV-2 positivity as a marker of sexual risk behavior in the study
      population. METHODS: This cross-sectional study included 423 blood donors of both
      sexes from eastern Croatia. Their blood samples were tested by ELISA IgG test kit
      for HSV-2 IgG and Western blot. Data on sexual risk behavior were collected by
      use of an anonymous questionnaire. RESULTS: Western blot testing showed HSV-2 IgG
      antibodies in 14 of 423 (3.3%) donor blood samples. The most common patterns of
      sexual risk behavior potentially associated with test positivity were irregular
      condom use during sexual intercourse with new partners (294/423; 69.5%) and > or
      = 5 sexual partners during lifetime (213/423; 50.4%). CONCLUSIONS: The population
      of blood donors from eastern Croatia included subgroups of subjects characterized
      by sexual risk behavior. Study results pointed to a relationship between various
      forms of sexual risk behavior and HSV-2 positivity, which could therefore serve
      as a reliable marker of sexual risk behavior in the study population.

PMID- 22372343
TI  - Multi point of care instrument evaluation for use in anti-retroviral clinics in
      South Africa.
AB  - BACKGROUND: South Africa has the largest prevalence of HIV infected individuals
      in the world. The introduction of point of care testing to anti-retroviral (ARV)
      clinic sites is hoped to fast track initiation of patients on ARVs and to allow
      for earlier recognition of adverse effects such as dyslipidaemia, renal and
      hepatic dysfunction. METHODS: We evaluated six instruments for the following
      analytes: glucose, lactate, creatinine, cholesterol, triglycerides, HDL
      cholesterol, alanine transaminase (ALT), and glycated haemoglobin. Comparisons
      with the central laboratory analyser were performed as well as precision studies.
      A scoring system was developed by the authors to evaluate the instruments in
      terms of analytical performance, cost, ease of use, and other operational
      characteristics. As one of the goals of the placement of these instruments was
      that their operation was simple enough to be used by non-laboratory staff, ease
      of use contributed a large proportion to the final scoring. RESULTS: Analytical
      performance of the POC analysers were generally similar, however, there were
      significant differences in operational characteristics and ease of use. Bias for
      the different analytes when compared to the laboratory analyser ranged from -27%
      to 14%. Calculated total errors for all analytes except for HDL cholesterol were
      within total allowable error recommendations. The two instruments (Roche
      Reflotron and Cholestech LDX) with the highest overall total points achieved the
      highest scores for ease of use. CONCLUSIONS: This pilot study has led to the
      development of a scoring system for the evaluation of POC instruments.

PMID- 22372344
TI  - Decreased expression of retinoblastoma protein-interacting zinc-finger gene 1 in
      human esophageal squamous cell cancer by DNA methylation.
AB  - BACKGROUND: To study the expression of the RIZ1 (Retinoblastoma protein
      interacting zinc-finger gene 1) gene and investigate the promoter region
      methylation status of RIZ1 gene in the human esophageal squamous cell carcinoma
      (ESCC) cell lines of KYSE150, KYSE510, TE13, EC9706, CaEsl7, and EC109. To
      investigate the influence of DNMT (DNA methyltransferase) 5-aza-CdR(5-aza-2'
      deoxycytidine) on the transcription of the RIZ1 gene in one cell line whose RIZ1
      gene promoter region methylation was detected, and to investigate its influence
      on the cell proliferation. METHODS: Real-time PCR (Real-time quantitative PCR)
      and an immunohistochemistry technique was used to get the expression of RIZ1 in
      specimens from 6 human ESCC cell lines and 28 ESCC patients (tumor tissues and
      adjacent non-cancerous tissues). MSP (Methylation-specific PCR) was used to
      investigate the promoter region methylation status of the RIZ1 gene in the 6 ESCC
      cell lines. One cell line, whose RIZ1 gene promoter region methylation was
      detected, was chosen for the next studies in which it was treated it by with 5
      aza-CdR. Real-time PCR was used to investigate its influence on the transcription
      of RIZ1 gene and MTT (methyl thiazolyl tetrazolium) was used to detect if 5-aza
      CdR inhibits the proliferation of the cell line. RESULTS: In the 28 ESCC patient
      samples, RIZ1 expression was significantly lower in the tumor tissues than that
      in their adjacent non-cancerous tissues (p < 0.05). Consistently,
      immunohistochemistry analyses of RIZ1 protein expression showed that in the ESCC
      tissues RIZ1 protein expression was also significantly lower than in the adjacent
      tissues. In the human ESCC tissues the rate of expression accounts for 0% (0/12),
      and in the adjacent noncancerous tissues the rate of expression was 66.7% (8/12),
      the correlation was highly significant (chi2 = 12.000, p < 0.05). Promoter
      methylation of the RIZ1 gene was detected in TE13, CaEsl7, EC109. The cell line
      TE13 was chosen for the next studies. The expression of RIZ1 mRNA in TE-13 was up
      regulated after having been treated with 5-aza-CdR. 5-aza-CdR inhibited cell
      proliferation of TE-13 in a time and concentration-dependent manner. CONCLUSIONS:
      Promoter methylation may play an important role in the epigenetic silencing of
      RIZ1 gene expression. Methylation of the RIZ1 promoter and loss of RIZ1
      expression in human ESCC are independent biomarkers. Their determination may
      offer guidance for selecting appropriate diagnoses and treatments. RIZ1 may be a
      potential tumor suppressor in human ESCC.

PMID- 22372345
TI  - T helper and B cell escape mutations within the HBc gene in patients with
      asymptomatic HBV infection: a study from the South-Eastern region of Iran.
AB  - BACKGROUND: Escape mutations potentially allow viruses to avoid detection and
      clearance by the host immune system and may represent a mechanism through which
      infections may persist in some patients. The association of the mutations in the
      HBcAg gene with Hepatitis B asymptomatic carriers (ASC) has not been studied
      adequately. The current study was aimed to investigate HBcAg18-27 CTL epitope
      mutations in ASC patients in the South-Eastern region of Iran. METHODS: 100 ASC
      patients were selected for this study and screened for HLA-A2 using flow
      cytometry. HBV-DNA was extracted from the HLA-A2 positive patients and the HBc
      gene was amplified using PCR. Direct double sequencing was performed to analyse
      mutations in the HBc gene of HBV isolates from patients with ASC. RESULTS:
      Overall, 25 (25%) of individuals were HLA-A2 positive. Direct double sequencing
      indicated no mutations in the HBcAg18-27 epitope. However, four mutations within
      the T helper and three mutations within the B cell epitopes of ASC patients were
      identified. CONCLUSIONS: The lack of mutations within the HBcAg18-27 epitope
      suggests that the antigenicity of this region is not altered in HBV isolates of
      our patients and therefore antigen presentation would occur normally to the
      patient's immune system through HLA-A2. However, in the course of this study we
      revealed some novel mutations within the T helper and B cell epitopes that may
      affect the efficiencies of immune response of ASC patients against these novel
      HBV epitopes.

PMID- 22372346
TI  - A real-time PCR assay for HPV52 detection and viral load quantification.
AB  - BACKGROUND: Human papillomavirus (HPV) 52 is one of the most frequent high risk
      HPV types found in cervical and anal infections. Reliable and well characterized
      methods for HPV 52 detection are therefore of great importance. Unfortunately one
      of the most widely used commercially available HPV typing assays, the Roche
      Linear Array (LA), detects type 52 only through its XR probe which cross-reacts
      with types 33, 35 and 58 and fails to give unambiguous detection of HPV 52.
      METHODS: To address this problem a real-time TaqMan PCR assay for HPV 52
      targeting the E6/E7 region was developed and validated, which can be applied as
      robust duplex assay simultaneously detecting beta-globin as genomic control and
      reference or as highly sensitive single target detection assay. RESULTS:
      Optimized primer and probe concentrations produced linear PCR amplifications over
      seven logs of targets (10(1) - 10(7)). The detection limit for HPV 52 was
      reproducibly at 10 copies per reaction for the duplex assay format and 5 copies
      for the single-plex format. The assay was very type-specific and no amplification
      signal was observed with 10(7) copies of the related HPV33, 35, and 58 DNA. Of 89
      samples that tested unambiguously positive for HPV 52 in the LA, 75 were
      confirmed in the duplex format and 88 in the single-plex format. An additional
      100 samples negative for HPV 52 in LA were all negative in both HPV 52 real-time
      PCR assay formats. CONCLUSIONS: These results indicate 92.6% and 99.5% accuracy
      relative to LA for the duplex and single-plex formats, respectively. In ongoing
      testing of 18,484 from various studies, 10.8% required the HPV52 TaqMan assay to
      unequivocally determine the status. Including the HPV 52 duplex assay provides
      the ability to monitor variations in the cell yield in various methods of sample
      collection and processing. This additional information is useful in QC monitoring
      of epidemiologic studies.

PMID- 22372347
TI  - Hemolysis is a major cause of variability in insulin measurement during oral
      glucose tolerance test in children.
AB  - BACKGROUND: The oral glucose tolerance test (OGTT) is widely employed to evaluate
      insulin resistance in children with growth hormone deficiency. Due to the
      difficulty in blood sampling, hemolysis is a frequent pre-analytic interference.
      The present study was performed to characterize the effects of hemolysis on
      insulin assays, in order to assess the need to generate automatic hemolysis
      reports and/or to reject hemolyzed samples. METHODS: Insulin plasma levels were
      measured using a Siemens ADVIA Centaur on samples obtained from children with
      suspected GH deficiency at risk for insulin resistance during OGTT. RESULTS: The
      presence of hemolysis (with a concentration of free hemoglobin above 75 mg/dL)
      promotes a dose- and time-dependent decrease in immunoreactive insulin at any
      time-point evaluated during OGTT. As a consequence, the variability of insulin is
      particularly high (often exceeding 100% of the mean value) as compared to that of
      glucose. This variability is markedly reduced after removal of the hemolyzed
      samples. CONCLUSIONS: When hemolysis is not taken into account a
      misinterpretation of insulin secretion pattern can occur. It is therefore
      imperative to: (i) analyze blood samples immediately after sampling, (ii) reject
      samples with a concentration of free hemoglobin equal to or above 125 mg/dL and
      (iii) always report the possible interference.

PMID- 22372348
TI  - Aquaporin 1 and aquaporin 4 are involved in invasion of lung cancer cells.
AB  - BACKGROUND: An oncogenic capacity of aquaporins (AQPs) has been recently
      proposed. They are channel-forming membrane proteins that function as osmotically
      driven transepithelial and transcellular water. Most recently, overexpression of
      several AQPs has been reported in different types of human cancer, which
      indicates that AQPs may play an important role in human carcinogenesis. METHODS:
      In this study, we were going to elucidate the involvement of aquaporin 1 and 4
      (AQP1,4) in the metastasis of lung cancer. RESULTS: Expression of AQP1,4 was
      examined by immunohistochemistry on the twenty lung cancer tissues. AQP1,4 were
      overexpressed in 65% (13 of 20) and 70% (14 of 20) of adenocarcinoma, while the
      normal lung tissues were negative. We next investigated the roles of AQP1,4 in
      the invasion of lung cancer cells by transwell migration assays. It is indicated
      that migration cells of the AQP1-shRNA or AQP4-shRNA were reduced significantly
      in comparison to the controls (AQP1- shRNA vs. AQP1-CTL, 5.6% vs. 15.9%, p <
      0.05; AQP4- shRNA vs. AQP4-CTL, 8.9% vs. 14.8%, p < 0.05). From this study, we
      found AQP1 and AQP4 in lung cancer cell extravasation and spread, which may
      provide a functional explanation for the expression of AQP1 and AQP4 in lung
      cancer tissues and lung cancer cell lines. CONCLUSIONS: Although further details
      on the molecular function of AQP1 or 4 related to tumorigenesis remain to be
      elucidated, our results suggest a potential role of AQP1 or 4 as novel
      therapeutic targets for the management of lung cancer.

PMID- 22372349
TI  - Improvement of lipid profile and reduction of body weight by shan he jian fei
      granules in high fat diet-induced obese rats.
AB  - BACKGROUND: The goal was to study lipid profiles (TG, TC, LDL, HDL), effects on
      serum leptin, and fat tissue adiponectin, and resistin as well as body weight
      effects of Shan He Jian Fei Granules (SHJFG) in rats on a high fat diet. METHODS:
      Rats were randomly divided into five groups: normal control group fed with normal
      fat diet, rats on high fat diet receiving low dosage, middle dosage, high dosage
      of Shan He Jian Fei Granules (SHJFG) as well as a high fat diet group receiving
      placebo. Rats were treated for 8 weeks. Body weight and naso-anal length of each
      rat were recorded and Lee's index was calculated. Serum TG, TC, LDL, HDL and
      leptin concentrations were analyzed. The gene expressions of adiponectin and
      resistin in adipose tissues were tested by RT-PCR. RESULTS: Compared to the high
      fat diet group, body weights, Lee's indexes, weight of fat tissues and serum TG,
      TC, LDL and leptin of SHJFG groups significantly decreased (p < 0.05), whereas
      mRNA expressions of adiponectin and resistin of SHJFG groups significantly
      increased (p < 0.05). CONCLUSIONS: SHJFG could significantly lower body weight
      and serum TG, TC, and LDL of obese rats. The effects of SHJFG in lowering leptin
      synthesis and raising mRNA expression of adiponectin and resistin in fat tissues
      may act as part of the mechanisms in lowering body weight of obese rats. Further
      studies are needed to demonstrate whether SHJFG may also reduce overall
      cardiovascular morbidity and mortality like other lipid lowering drugs.

PMID- 22372350
TI  - Total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric
      oxide concentrations in patients with severe persistent allergic asthma: its
      relation to omalizumab treatment.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease and omalizumab is indicated
      for moderate-to-severe persistent asthma. The results of many studies have shown
      that oxidative stress is involved in asthma pathogenesis. However, there is no
      data available to evaluate the alterations in total antioxidant capacity,
      hydrogen peroxide, malondialdehyde, and total nitric oxide concentrations.
      OBJECTIVES: The objective was to determine whether treatment with omalizumab in
      severe allergic asthma influences systemic levels of oxidative stress markers.
      METHODS: The first group of 14 patients included 6 male and 8 female subjects
      with severe persistent asthma, having a mean age of 42.4 years. The second group
      included 14 newly diagnosed allergic asthma patients with a mean age of 43.8
      years. All patients were followed in the Immunology and Allergy Clinic of the
      Antalya Education and Training Hospital and were evaluated by clinical status. A
      third group of 14 age-sex matched healthy controls were also included. Serum
      samples were collected and stored at -70 degrees C until use for the
      determination of total antioxidant capacity, hydrogen peroxide, malondialdehyde,
      and total nitric oxide concentrations. Serum IgE levels, ANA (antinuclear
      antibody), RF (rheumatoid factor), hepatitis markers, C3, C4, and eosinophil
      levels were evaluated in all patients. All assays were carried out in duplicate.
      RESULTS: The mean IgE levels were as follow: Group I: 459.785 IU/mL; Group II:
      124.8 IU/mL, and Group III: 39.88 IU/mL. Total antioxidant capacity levels of
      Group IB, group II, and group III were lower than the IA group. Total antioxidant
      capacity levels of groups II and III were higher than in group IB. Hydrogen
      peroxide concentrations in group IB were lower than in group IA, while
      concentrations in group II were higher than in group IB. The malondialdehyde
      concentration of group IB was lower than in all other groups. The malondialdehyde
      concentration of group III was higher than all other groups. The malondialdehyde
      concentration of group II was lower than in group III. The total nitric oxide
      level of group IB was lower than all other groups. The total nitric oxide level
      of group III was higher than all other groups, while that of group II was higher
      than for both groups IA/IB. CONCLUSIONS: To monitor the omalizumab treatment
      efficacy in severe allergic asthma patients, total antioxidant capacity, hydrogen
      peroxide, malondialdehyde, and total nitric oxide concentrations might be new
      markers.

PMID- 22372351
TI  - Method comparison for determination of the tumor markers AFP, CEA, PSA and free
      PSA between Immulite 2000 XPI and Dimension Vista 1500.
AB  - BACKGROUND: For the Luminescent Oxygen Channeling Immunoassay (LOCI) technology
      as established for Dimension Vista 1500, assays have been developed for the serum
      tumor markers AFP, CEA, PSA and free PSA. We performed a method analysis for
      these parameters using the Immulite 2000 XPI. METHODS: Determination of within
      day and total imprecision of the methods was carried out according to CLSI
      guidelines with three serum pools. In addition, parallel measurements were
      performed with both systems in 1,871 routine serum samples and correlations were
      calculated. RESULTS: Calculated total imprecision of the three serum pools for
      AFP was 3.8 - 4.3%, for CEA 3.3 - 4.3%, for tPSA 3.6 - 4.0% and for fPSA it was
      3.5 - 8.2%. Correlations of these markers across the entire value range were very
      good with the following correlation coefficients: 0.997 for AFP, 0.996 for CEA,
      0.971 for tPSA and 0.988 for fPSA. While values for AFP and tPSA from both
      methods were comparable (slopes 1.02 and 1.01), lower values were measured for
      CEA and fPSA with the Dimension Vista (slopes 0.83 and 0.91). For AFP, a sample
      cluster with considerably higher values than with Dimension Vista was observed in
      the lower measurement range (< 20 ng/mL). CONCLUSIONS: The assays for AFP, CEA,
      tPSA and fPSA, as developed with the LOCI technology for the Dimension Vista,
      show good comparability with results obtained from the Immulite 2000 XPI.
      However, lower measurement ranges for CEA and fPSA as well as individual
      divergences, especially with AFP, must be taken into consideration in the event
      of method changeover.

PMID- 22372352
TI  - Analytic performance of bacteriuria and leukocyturia obtained by UriSed in
      culture positive urinary tract infections.
AB  - BACKGROUND: Urine analysis is one of the most common tests for assessing urinary
      tract infections, which are the most frequently occurring infectious diseases in
      community populations. Urine culture is still the 'gold standard' for the
      detection of urinary tract infection, however, it is time- and labor-intensive
      and and has a high number of unnecessary cultures. The aim of this study was to
      evaluate the analytical and diagnostic performance of a new urinalysis system
      LabUMat with UriSed (77 Elektronika, Budapest, Hungary) in comparison to urine
      culture as the reference method. METHODS: By comparing the test results for 965
      urine samples with quantitative urine cultures, we established cutoff criteria
      for the UriSed. The cut-off values by the receiver operating characteristic (ROC)
      curve technique, sensitivity, and specificity were calculated for bacteria (BACT)
      and white blood cells (WBCs). RESULTS: A bacterial cutoff value of 375/microL
      provided the best discrimination for community-acquired urinary tract infection,
      with a sensitivity of 96.5% and a specificity of 82.1% compared with 182 urine
      culture positive samples (AUC: 0.939). It was possible to forgo 62.6% of cultures
      with only 8 false-negative results. The best cut-off value for WBCs was
      13/microL. When we used an algorithm in which the combination with the positivity
      for 85 BACT/microL and for 13 WBCs/microL count, the sensitivity and NPV improved
      to 99.8% and 100%, respectively, but the specificity declined from 78.8% to
      52.0%. CONCLUSIONS: When screening with the UriSed for community-acquired urinary
      tract infection, a cut-off value of 85 bacteria/microL and 13 WBCs/microL should
      be adopted. Diagnostic performance of UriSed is satisfactory and use of this
      instrument is a reliable method for screening out a major part of the culture
      negative samples. It would improve the efficiency of microbiology laboratory, and
      unnecessary antibiotic prescriptions could be reduced.

PMID- 22372353
TI  - Clinical significance of serum CA125 in nephrotic syndrome.
AB  - BACKGROUND: To investigate the clinical significance of serum CA125 in the
      patients with nephrotic syndrome (NS). METHODS: Three hundred and twenty-two
      patients with NS and 120 healthy volunteers were enrolled in our study. We
      measured serum CA125 and analyzed the probable relationship between elevated CA
      125 levels in patients with NS, with and without ascites. Ascites were determined
      by B-mode ultrasonography in patients with NS. RESULTS: Serum CA-125 in NS
      patients with ascites was significantly increased compared to NS patients without
      ascites (p < 0.05). There was no statistically significant difference between the
      healthy volunteers and the patients without ascites (p > 0.05). CONCLUSIONS:
      Serum CA125 is a useful index in the diagnosis of ultrasonographically detected
      ascites in patients with NS.

PMID- 22372354
TI  - A wide variety of diarrhea viruses circulating in pediatric patients in Thailand.
AB  - BACKGROUND: Viral gastroenteritis has been recognized as one of the most common
      illnesses that affects infants and young children all over the world. A wide
      variety of viruses associated with the disease are continually being reported. To
      investigate the epidemiological situation of diarrhea virus infection in Chiang
      Mai, Thailand, surveillance was conducted during January to December 2007.
      METHODS: A total of 160 fecal specimens collected from pediatric patients
      admitted to the hospital with acute gastroenteritis were tested for the presence
      of group A, B, and C rotaviruses, norovirus, sapovirus, astrovirus, adenovirus,
      Aichi virus, enterovirus, bocavirus, and human parechovirus by RT-multiplex PCR.
      RESULTS: Of 160 fecal specimens tested, 85 (53.1%) were positive for diarrhea
      viruses. Of these, group A rotavirus was the predominant with a prevalence of
      27.5%, followed by norovirus GII (11.9%), sapovirus (3.1%), enterovirus (2.5%),
      human parechovirus (1.9%), and norovirus GI, astrovirus, adenovirus (each 0.6%).
      Mixed-infections of 2 or 3 viruses were observed in 7 (4.4%) patients. However,
      none of groups B and C rotaviruses and Aichi virus were detected in this study.
      Monthly distribution analysis revealed that all those diarrhea viruses were
      detected continually throughout the year at a low level of infection except for
      group A rotavirus and norovirus infections which appeared to peak in a cool
      season in January-March and December, respectively. CONCLUSIONS: This
      surveillance revealed a wide variety of diarrhea viruses currently circulating in
      pediatric patients with acute gastroenteritis in Chiang Mai, Thailand.

PMID- 22372355
TI  - The usefulness of myeloperoxidase in prediction of in-hospital mortality in
      patients with ST-segment elevation myocardial infarction treated by primary
      percutaneous coronary intervention.
AB  - BACKGROUND: The predictive value of myeloperoxidase (MPO) in ST-segment elevation
      myocardial infarction (STEMI) treated by primary percutaneous coronary
      intervention (PCI) has not been established. The aim of the present study was to
      investigate MPO as a predictor of in-hospital mortality in STEMI patients treated
      by primary PCI. METHODS: Study population consisted of 189 STEMI patients having
      undergone primary PCI. Plasma MPO level was measured 24 hours after symptom onset
      using chemiluminescent microparticle immunoassay (Abbott Diagnostics, Germany).
      The Receiver Operating Characteristic analysis was performed to identify the most
      useful MPO cut-off level for the prediction of in-hospital mortality. The
      patients were divided into two groups according to the cut-off MPO level: high
      MPO group (> or = 840 pmol/L, n = 65) and low MPO group (< 840 pmol/L, n = 124).
      RESULTS: The high MPO group had significantly more frequent anterior wall
      infarctions (p < 0.001) and Killip class > 1 on admission (p = 0.013) as well as
      lower left ventricular ejection fraction (LVEF) (p = 0.011) and higher B-type
      natriuretic peptide (BNP) (p = 0.029) than the low MPO group. The incidence of in
      hospital mortality was 5.8% and was significantly higher in the high MPO group
      (13.8%) than in the low MPO group (1.6%) (p = 0.001). Multiple logistic
      regression analysis identified the plasma MPO level as an independent predictor
      of in-hospital mortality (OR 3.88, 95% CI 1.13 - 13.34, p = 0.031). CONCLUSIONS:
      Plasma MPO level independently predicts in-hospital mortality in STEMI patients
      treated by primary PCI.

PMID- 22372356
TI  - The use of an immunocytochemical double-labeling staining can display the
      distribution of Bcl-2/Ki-67 cells in endometrial adenocarcinomas as well as in
      normal endometrium.
AB  - BACKGROUND: Endometrial adenocarcinoma is the most common gynecologic malignancy
      and is the fifth most frequently diagnosed cancer in women. The objective of the
      present study was to determine the expression of a proliferation marker, Ki-67
      and an apoptosis inhibitor, Bcl-2, by double-label staining in endometrial
      adenocarcinomas and in normal endometrium samples, to evaluate the differences in
      the immunocytochemical expression of Ki-67 and Bcl-2, and finally to correlate
      the results with tumor grade and stage. METHODS: This study was carried on 270
      endometrial samples, collected during a 27 month period, freshly resected from
      women who underwent total abdominal hysterectomy. RESULTS: Ki-67 and Bcl-2
      expressions were studied by immunocytochemistry. Bcl-2 expression was strong and
      homogeneous in normal (proliferative, secretory and atrophic) endometrium and
      more frequent in low-grade endometrioid carcinomas. Completely negative staining
      of Bcl-2 was found to be strictly related to high-grade endometrioid carcinomas.
      Ki-67 expression was higher in patients with high-grade endometrioid carcinomas.
      Proliferative endometrium showed inconclusive Ki-67 expression levels and in the
      secretory endometrium Ki-67 positive cells were remarkably diminished and even
      disappeared. Completely negative staining of Ki-67 was found to be strictly
      related to atrophic endometrium. CONCLUSIONS: Immunocytochemical double-label
      staining can be used to display the distribution of Bcl-2 and Ki-67 cells in
      endometrioid carcinomas as well as normal endometrium, and, in addition to
      cytomorphologic features, contributes to its accurate diagnosis.

PMID- 22372357
TI  - Value of lipopolysaccharide binding protein, interleukin-6 and C-reactive protein
      as biomarkers of severity in acute diverticulitis: a prospective study.
AB  - BACKGROUND: New biomarkers have the capability to predict severity and outcome of
      infectious diseases. Lipopolysaccharide binding protein (LBP) and Interleukin 6
      (IL-6) were determined as new markers in patients with acute diverticulitis and
      were compared with standard markers such as C-reactive protein (CRP) and white
      blood cell count (WBC). METHODS: CRP, IL-6, WBC and LBP were measured in 38
      patients at hospital admission and every second day and after colonoscopy. Multi
      slice CT scans, ultrasound and early colonoscopy were performed to confirm
      diagnosis and to detect complications (perforations, stenosis). RESULTS: CRP, IL
      6 and LBP levels one correlated highly with each other and were equally
      influenced by antibiotic therapy. WBC changes were unremarkable. Severity of the
      disease (sealed- or non-perforation) was not reflected by the biomarkers. In non
      perforated patients, colonoscopy was performed on day 6 (median) after admission
      with a success rate of 93%. Sealed-perforated patients were examined on median
      day 11 with a success rate of 60% (p > 0.001). Failure in all cases was due to
      sigmoidal stenosis requiring surgery. In a receiver-operating characteristic
      curve analysis (ROC), LBP on day one performed best in predicting colonic steno
      sis with an area under the curve of 0.88 (95% CI 0.73 - 0.03 p < 0.02).
      CONCLUSIONS: CRP, IL-6, and LBP can be used to monitor diverticulitis. Initial
      LBP values in patients with acute diverticulitis may also be usefully in
      detecting candidates for surgical intervention.

PMID- 22372358
TI  - Calibration verification for Olympus and Hitachi automatic biochemistry analyzers
      using albumin.
AB  - BACKGROUND: The validity of calibration settings is confirmed by testing
      materials of known concentration in the same manner as patient specimens to
      assure the test system is accurate throughout the reportable range. CLIA'88
      states calibration verification procedures are required to confirm the continued
      accuracy of the test system throughout the laboratory's reportable range of test
      results. METHODS: In accordance with the instruments used, the albumin data were
      divided into either the Olympus or the Hitachi groups. The performance of
      calibration verification was based on the approach of calibration verification
      currently used by the College of American Pathologists (CAP), i.e., the slope and
      intercept of the calibration line were tested by a one-sample t test, the percent
      difference was calculated and was compared with allowable error. RESULTS: In the
      Olympus group, verified 1, different 1, verified 2, and different 2 were 5.6%,
      0%, 60.6%, and 33.8%, respectively. In the Hitachi group, verified 1, different
      1, verified 2, and different 2 were 4.5%, 1.5%, 58.2%, and 35.8%, respectively.
      CONCLUSIONS: The method of calibration verification used by the CAP was
      reasonable and feasible. In this study, 64.5% of participating laboratories
      passed the evaluation of calibration verification for the Olympus and Hitachi
      analyzers using albumin.

PMID- 22372359
TI  - High copper and low zinc serum levels in Iranian patients with multiple
      sclerosis: a case control study.
AB  - BACKGROUND: The purpose of this study was to evaluate the levels of zinc (Zn) and
      copper (Cu) in the serum of Iranian patients with multiple sclerosis (MS).
      METHODS: The serum levels of zinc (Zn) and copper (Cu) were measured in sixty
      Iranian patients with MS and compared with sixty age-, gender- and socioeconomic
      status-matched healthy subjects without any neurological disorders as controls
      from the same geographical area. RESULTS: Significantly lower serum Zn and higher
      serum Cu levels were found in the MS patients compared with the controls (p <
      0.0001 and p = 0.002, respectively). The serum Zn level of the secondary
      progressive MS patients was significantly lower compared with the relapsing
      remitting MS patients (p = 0.009). There was no significant difference between
      the serum Cu levels of the two subgroup of MS patients (p = 0.42). CONCLUSIONS:
      The results suggest significant deviations of the Iranian MS patients' serum Zn
      and Cu levels from the norm.

PMID- 22372360
TI  - Selenium levels in persons with HIV/tuberculosis in India, Madurai City.
AB  - BACKGROUND: Selenium plays a vital role in the immune status of the individual.
      The prospective observational study was conducted from September 2009 to March
      2010. The aim of the present study is to investigate the association between
      serum selenium levels and pulmonary tuberculosis (PTB) patients with (n = 40) and
      without HIV (n = 40) in comparison to healthy controls (healthy family members; n
      = 20) who satisfied rigid selection criteria. METHODS: Standard methods were
      adopted to collect an early morning fasting blood sample for serum selenium
      concentrations, determined by atomic absorption spectrometry (AAS), and albumin,
      determined by the bro mocresol green method. RESULTS: The mean +/- SD for Body
      Mass Index (BMI), selenium, and albumin among the controls, HIV positive, and HIV
      negative patients were 19.6 +/- 0.6, 18 +/- 0.4 and 18.5 +/- 0.6 kg/m2; 113.1 +/-
      4.1, 27.44 +/- 8, and 65.92 +/- 9, microg/dL; and 4.1 +/- 0.6, 2.9 +/- 0.4 and
      3.6 +/- 0.7 g/dL, respectively. BMI, serum selenium, and albumin levels were
      found to be significantly lower (p < 0.004, p < 0.0321, and p < 0.002,
      respectively). CONCLUSIONS: Low serum selenium levels are associated with
      increased risk of pulmonary infection caused by mycobacteria.

PMID- 22372361
TI  - Effect of temperature on albumin cobalt binding and its influence on ischemia
      modified albumin levels in patients with suspected acute coronary syndrome.
AB  - BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be a rapidly rising
      and sensitive biochemical marker especially for the diagnosis of myocardial
      ischemia. The aim of this study was to evaluate the influence of temperature on
      the capacity of cobalt binding to human albumin and the influence of this
      variable on IMA measurement. METHODS: The following temperatures of incubation
      were tested for human albumin standard 25 degrees C, 28 degrees C, 31 degrees C,
      34 degrees C, and 37 degrees C and for patients with suspected acute coronary
      syndrome, room temperature and 37 degrees C. IMA was measured by cobalt-albumin
      binding assay. RESULTS: There was a strong positive correlation (r = 0.98, p <
      0.001) between IMA and the assay temperatures. IMA levels were 0.68 +/- 0.25
      absorbance units (ABSU) at room temperature and 0.92 +/- 0.33 ABSU (p < 0.001) at
      37 degrees C in the study participants. CONCLUSIONS: IMA values were influenced
      by the assay temperature.

PMID- 22372362
TI  - Genotype distribution in chronic hepatitis C patients in Greece.
AB  - BACKGROUND: Hepatitis C is a major public health problem. HCV infection
      contributes to progressive liver disease, cirrhosis, and hepatocellular
      carcinoma. HCV has high genetic heterogeneity and is classified into various
      genotypes and subtypes. Regional differences exist in their distribution. The aim
      of this study was to investigate the relative frequency of HCV genotypes in Greek
      patients with chronic infection. METHODS: We evaluated 82 patients with chronic
      HCV infection, both males and females, belonging to different risk groups. We
      performed viral load measurement and HCV genotyping in all specimens. RESULTS:
      HCV genotype 3 was the most prevalent (41.5%) followed by genotype 1 (34.1%), 2
      (12.2%), 4 (10.9%), and 5 (1.2%). Genotype 6 was not detected in any patient.
      Most prevalent subtypes were 3a (32.9%), 1b (26.8%), and 2a (6.1%). Fourteen
      subjects revealed mixed infections within types. There were no cases with mixed
      infections across types. CONCLUSIONS: Our data indicate that genotypes 3a and 1b
      are the most prevalent in Greek patients. Genotype 3a is predominant in younger
      patients and also in male patients. Moreover, HCV genotype distribution is in
      continuous temporal change in Greece.

PMID- 22372363
TI  - The purification step is not crucial in EIA measurements of thromboxane B2 and 11
      dehydrothromboxane B2 in human plasma.
AB  - BACKGROUND: Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11
      dTxB2) are widely used as prognostic risk markers of platelet activation in
      cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination
      include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2
      (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately
      5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this
      study was to investigate the impact of a widely used purification step on the
      results of enzyme immunosorbent assay (EIA)--based measurement of the two
      selected thromboxanes. METHODS: For the purpose of this study, 20 plasma samples
      (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were
      screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA
      kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or
      without the introduction of the purification procedure. RESULTS: The purification
      step does not significantly affect the results of EIA measurements of the two of
      TxA2 metabolites (TxB2, 11-dTxB2) in human plasma. The levels of TxB2 and 11
      dTxB2 determined in the plasma samples were not significantly changed (p < 0.05)
      when the purification step was omitted compared to the purified samples.
      CONCLUSIONS: This study establishes a protocol allowing for reliable and
      reproducible plasma TxB2 and 11-dTxB2 EIA measurement for routine basic screening
      of platelet function.

PMID- 22372364
TI  - Human Duffy blood group alloantigen system influences the measurement of monocyte
      chemoattractant protein-1 (MCP-1) in serum but not in plasma.
AB  - BACKGROUND: We explored whether the Asp42Gly polymorphism (rs12075) in the DARC
      gene represents a confounding factor in the interpretation of monocyte
      chemoattractant protein-1 (MCP-1) concentration in circulating blood. METHODS:
      MCP-1 concentration in serum and plasma were measured in 278 healthy Caucasian
      participants who are representative of our geographic area. The rs12075 genotype
      distribution was also assessed in this population. RESULTS: Plasma MCP-1
      concentration did not vary among the rs12075 polymorphism derived genotypes [in
      pg/mL, AA: 171.9 (100.2 - 287.2), AG: 178.9 (105.1 - 326.4) and GG: 173.7 (94.4 -
      405.7)]. However, there were significant increases in serum MCP-1 related to the
      presence of the A allele [in pg/mL, AA: 334.6 (180.4 - 756.4), AG: 299.1 (166.1 -
      634.9) and GG: 249.1 (149.3 - 578.1)]. CONCLUSIONS: These findings limit the
      value of circulating MCP-1 as a biomarker and apparently indicate a
      pathophysiological role for silent chemokine receptors.

PMID- 22372365
TI  - One half living for two: cross-cultural paradigms of twinship and twin loss.
AB  - Many indigenous African religions, specifically that of the Yoruba of Nigeria,
      the Bamana and Malinke of Mali, and the Nuer of southern Sudan, are characterized
      by a system of spiritual beliefs surrounding the life and death of twins.
      Separation by death poses an extreme threat to the soul(s) of twins, and many
      rituals and customs designed to sustain the spirit of surviving twins are widely
      practiced. Despite twin loss being overlooked in Western psychological studies of
      grief, recent research and in-depth interviews of bereaved twins clearly
      identifies the unique nature of losing a twin, and the importance of
      acknowledging this distinction in the surviving twin's ability to cope with the
      death. The spiritual practices of the Yoruba, Bamana, Malinke, and Nuer are
      conducive to dealing with the specific nature of twin loss. They take into
      account the uniqueness of the twinship experience, and provide material for
      reflection on healing approaches outside the traditional parameters of
      psychology.

PMID- 22372366
TI  - The Chinese version of the multidimensional orientation toward dying and death
      inventory (MODDI-F/chin): an introduction.
AB  - Preliminary data on the test criteria of the Chinese version of the
      Multidimensional Orientation Toward Dying and Death Inventory (MODDI-F/chin) are
      presented. Data from a sample of Hong Kong college students (N = 256) revealed
      internal consistencies of the eight subtests between .68 and .91, on the whole
      favorable shape of frequency distributions, and evidence of construct as well as
      differential validity of the instrument. The use of the full set of 47 items is
      recommended for the time being.

PMID- 22372367
TI  - "Almost the copy of my child that's dead": Shakespeare and the loss of Hamnet.
AB  - This article emphasizes the importance of studies which look at changes and
      similarities in mourning over time. It argues that relevant evidence can come
      from creative fiction as well as from other sources, provided that this is
      analyzed rigorously in terms of structures and patterns. As an illustration of
      this approach, it examines the evidence in recurring features of Shakespeare's
      plays that his writing was deeply and lastingly affected by the death of his only
      son Hamnet, a twin, at the age of 11, and identifies five motifs which support
      this interpretation: the resurrected child or sibling; androgynous and twin-like
      figures; a growing emphasis on father-daughter relationships; paternal guilt;
      family division and reunion. The article suggests that this approach could be
      applied to other instances where a body of creative writing shows traces of overt
      or buried grief.

PMID- 22372368
TI  - Parental bereavement: a panoramic view.
AB  - This study is aimed at identifying central themes of bereavement. A qualitative
      approach was employed in the analyses of interviews with 22 bereaved parents. The
      analyses yielded four central issues or themes of bereavement, each with its own
      set of sub-themes or categories, as the narrative demanded. The first of these
      themes, pertaining to the life of the family before the death of a child had
      taken place, was named the risk factor. Circumstances leading up to the death,
      surrounding the death, the cause of death, and the events following the death
      were coded as bereavement circumstances. The grief reactions codes were divided
      into categories of emotional, physical, behavioral, relational, spiritual, and
      cognitive reactions, as described by the participants. Finally, the mourning
      codes described the mechanisms employed by the participants in their attempts to
      survive and continue living after the death. These findings can be used in the
      training of support workers and the development of bereavement interventions.

PMID- 22372369
TI  - Family members' experiences with viewing in the wake of sudden death.
AB  - Sudden deaths leave families in crisis and interacting with many professionals
      from notification through to burial. Whether to view the deceased is often
      central to discussion. Practice guidelines have evolved over time regarding
      where, when, how, and why viewing should or should not occur. Unfortunately,
      there is much contradiction in existing recommendations and a marked absence of a
      supporting evidence base for the practice of viewing itself, and the influence of
      this practice on the overall bereavement process. Using a qualitative approach,
      this study explored the perspectives and experiences of the suddenly bereaved
      with respect to: viewing or not having viewed; whether or not their viewing
      experiences have impacted on their bereavement process; and explored particular
      aspects of their experience such as interactions with various professionals.
      Results of this study are clustered and presented under three core themes:
      viewing specifics; intrapersonal responses; and professional interactions.

PMID- 22372370
TI  - The cultural meaning of suicide: what does that mean?
AB  - Scholars sometimes stress that it is important to know the individual meaning of
      suicide and the cultural meaning of suicide, but the meaning of these terms
      remains unclear. The present article discusses this problem and suggests that the
      individual meaning of suicide is best based on the motives for suicide, while the
      cultural meaning of suicide is best rooted in the lay theories of suicide in
      which the members of cultures and subcultures believe.

PMID- 22372371
TI  - Role of the Tyr-Cys cross-link to the active site properties of galactose
      oxidase.
AB  - The catalytically relevant, oxidized state of the active site [Cu(II)-Y.-C] of
      galactose oxidase (GO) is composed of antiferromagnetically coupled Cu(II) and a
      post-translationally generated Tyr-Cys radical cofactor [Y.-C]. The thioether
      bond of the Tyr-Cys cross-link has been shown experimentally to affect the
      stability, the reduction potential, and the catalytic efficiency of the GO active
      site. However, the origin of these structural and energetic effects on the GO
      active site has not yet been investigated in detail. Here we present copper and
      sulfur K-edge X-ray absorption data and a systematic computational approach for
      evaluating the role of the Tyr-Cys cross-link in GO. The sulfur contribution of
      the Tyr-Cys cross-link to the redox active orbital is estimated from sulfur K
      edge X-ray absorption spectra of oxidized GO to be about 24 +/- 3%, compared to
      the values from computational models of apo-GO (15%) and holo-GO (22%). The
      results for the apo-GO computational models are in good agreement with the
      previously reported value for apo-GO (20 +/- 3% from EPR). Surprisingly, the Tyr
      Cys cross-link has only a minimal effect on the inner sphere, coordination
      geometry of the Cu site in the holo-protein. Its effect on the electronic
      structure is more striking as it facilitates the delocalization of the redox
      active orbital onto the thioether sulfur derived from Cys, thereby reducing the
      spin coupling between the [Y.-C] radical and the Cu(II) center (752 cm(-1))
      relative to the unsubstituted [Y.] radical and the Cu(II) center (2210 cm(-1)).
      Energetically, the Tyr-Cys cross-link lowers the reduction potential by about 75
      mV (calculated) allowing a more facile oxidation of the holo active site versus
      the site without the cross-link. Overall, the Tyr-Cys cross-link confers unique
      ground state properties on the GO active site that tunes its function in a
      remarkably nuanced fashion.

PMID- 22372372
TI  - Full-color tunable photoluminescent ionic liquid crystals based on tripodal
      pyridinium, pyrimidinium, and quinolinium salts.
AB  - Color-tunable luminescent ionic liquid crystals have been designed as a new
      series of luminescent materials. To achieve tuning of emission colors,
      intramolecular charge transfer (ICT) character has been incorporated into
      tripodal molecules. A series of the compounds has three chromophores in each
      molecule, incorporated with both electron-donating moieties such as
      alkylaminobenzene and alkoxybenzene, and electron-accepting moieties such as
      pyridinium, pyrimidinium, and quinolinium parts. These C(3)-symmetrical molecules
      self-assemble into liquid-crystalline (LC) columnar (Col) structures over wide
      temperature ranges through nanosegregation between ionic moieties and nonionic
      aliphatic chains. Photoluminescent (PL) emissions of these tripodal molecules are
      observed in the visible region both in the self-assembled condensed states and in
      solutions. For example, a pyrimidinium salt with didodecylaminobenzene moieties
      exhibits yellowish orange emission (lambda(em) = 586 nm in a thin film).
      Multicolor PL emissions are successfully achieved by simple tuning of changing
      electron-donating and electron-accepting moieties of the compounds, covering the
      visible region from blue-green to red. It has been revealed that ICT processes in
      the excited states and weak intermolecular interactions play important roles in
      the determination of the PL properties of the materials, by measurements of UV
      vis absorption and emission spectra, fluorescence lifetimes, and PL quantum
      yields.

PMID- 22372373
TI  - Excellent outcome of matched unrelated donor transplantation in paediatric
      aplastic anaemia following failure with immunosuppressive therapy: a United
      Kingdom multicentre retrospective experience.
AB  - We retrospectively analysed the outcome of consecutive children with idiopathic
      severe aplastic anaemia in the United Kingdom who received immunosuppressive
      therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell
      transplantation (HSCT). The 6-month cumulative response rate following rabbit
      antithymocyte globulin (ATG)/ciclosporin (IST) was 32.5% (95% CI 19.3-46.6) (n =
      43). The 5-year estimated failure-free survival (FFS) following IST was 13.3%
      (95% confidence interval [CI] 4.0-27.8). In contrast, in 44 successive children
      who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an
      excellent estimated 5-year FFS of 95.01% (95% CI 81.38-98.74). Forty of these
      children had failed IST previously. HSCT conditioning was a fludarabine,
      cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy.
      There were no cases of graft failure. Median donor chimerism was 100% (range 88
      100%). A conditioning regimen, such as FCC that avoids total body irradiation is
      ideally suited in children. Our data suggest that MUD HSCT following IST failure
      offers an excellent outcome and furthermore, if a suitable MUD can be found
      quickly, MUD HSCT may be a reasonable alternative to IST.

PMID- 22372374
TI  - HIV latency: experimental systems and molecular models.
AB  - Highly active antiretroviral therapy (HAART) has shown great efficacy in
      increasing the survival of HIV infected individuals. However, HAART does not lead
      to the full eradication of infection and therefore has to be continued for life.
      HIV persists in a transcriptionally inactive form in resting T cells in HAART
      treated patients and can be reactivated following T-cell activation. These
      latently infected cells allow the virus to persist in the presence of HAART.
      Here, we review recent advances in the study of the molecular mechanisms of HIV
      latency. We also review experimental models in which latency is currently
      studied. We focus on the epigenetic mechanisms controlling HIV transcription and
      on the role of chromatin and its post-translational modifications. We discuss how
      small molecule inhibitors that target epigenetic regulators, such as HDAC
      (histone deacetylase) inhibitors, are being tested for their ability to
      reactivate latent HIV. Finally, we discuss the clinical potential of these drugs
      to flush out latently infected cells from HIV-infected patients and to eradicate
      the virus.

PMID- 22372375
TI  - NMR studies of the interaction between human programmed cell death 5 and human
      p53.
AB  - Human programmed cell death 5 (PDCD5) is a protein playing a significant role in
      regulating both the apoptotic and paraptotic cell deaths. Resent findings show
      that PDCD5 is a positive regulator of Tip60 and also has a potential ability to
      interact with p53. Here we aim to experimentally characterize the nature of the
      interactions between PDCD5 and the p53 N-terminal domain (NTD) and to depict the
      binding mode between two proteins. The interprotein binding interfaces were
      determined by NMR experiments performed with PDCD5 and various fragments of p53
      NTD. The binding affinity was investigated using the NMR titration experiments.
      Analysis revealed that the PDCD5 binding site on p53 is localized within residues
      41-56 of p53 TAD2 subdomain while p53 binds preferentially to the positively
      charged surface region around the C-terminals of helices alpha3 and alpha5 and
      the N-terminal of helix alpha4 of PDCD5. The binding is mainly mediated through
      electrostatic interactions. The present data suggested a model for the
      interaction between PDCD5 and the p53 NTD.

PMID- 22372376
TI  - To adopt is to adapt: the process of implementing the ICF with an acute stroke
      multidisciplinary team in England.
AB  - PURPOSE: The success of the International Classification of Functioning,
      Disability and Health (ICF) depends on its uptake in clinical practice. This
      project aimed to explore ways the ICF could be used with an acute stroke
      multidisciplinary team and identify key learning from the implementation process.
      METHOD: Using an action research approach, iterative cycles of observe, plan, act
      and evaluate were used within three phases: exploratory; innovatory and
      reflective. Thematic analysis was undertaken, using a model of immersion and
      crystallisation, on data collected via interview and focus groups, e-mail
      communications, minutes from relevant meetings, field notes and a reflective
      diary. RESULTS: Two overall themes were determined from the data analysis which
      enabled implementation. There is a need to: (1) adopt the ICF in ways that meet
      local service needs; and (2) adapt the ICF language and format. CONCLUSIONS: The
      empirical findings demonstrate how to make the ICF classification a clinical
      reality. First, we need to adopt the ICF as a vehicle to implement local service
      priorities e.g. to structure a multidisciplinary team report, thus enabling
      ownership of the implementation process. Second, we need to adapt the ICF
      terminology and format to make it acceptable for use by clinicians.

PMID- 22372377
TI  - Targeting of Cameleons to various subcellular compartments reveals a strict
      cytoplasmic/mitochondrial Ca2+ handling relationship in plant cells.
AB  - Here we describe use of a mitochondrial targeted Cameleon to produce stably
      transformed Arabidopsis plants that enable analyses of mitochondrial Ca2+
      dynamics in planta and allow monitoring of the intra-mitochondrial Ca2+
      concentration in response to physiological or environmental stimuli. Transgenic
      plants co-expressing nuclear and mitochondrial targeted Cameleons were also
      generated and analyzed. Here we show that mitochondrial Ca2+ accumulation is
      strictly related to the intensity of the cytoplasmic Ca2+ increase, demonstrating
      a tight association between mitochondrial and cytoplasmic Ca2+ dynamics. However,
      under all experimental conditions, mitochondrial Ca2+ dynamics were substantially
      different from those monitored in the cytoplasm, demonstrating that mitochondria
      do not passively sense cytosolic Ca2+, but actively modulate the intra
      mitochondrial level of the cation. In particular, our analyses show that the
      kinetics of Ca2+ release from mitochondria are much slower than in the cytoplasm
      and nucleus. The mechanisms and functional implications of these differences are
      discussed.

PMID- 22372378
TI  - Improved survival trend of patients with hepatocellular carcinoma at an
      Australian tertiary hospital between 1995-2009.
AB  - AIM: To evaluate trends in survival of patients with hepatocellular carcinoma
      (HCC) at The Alfred over a 15-year period from 1995-2009 METHODS: A retrospective
      cohort study of patients with HCC comparing epidemiology, clinical presentation,
      treatment parameters and overall survival of those diagnosed between 1995-2001
      and 2002-2009. Overall survival of patients with primary liver cancer. RESULTS:
      The study population consisted of 215 patients; 110 diagnosed between 1995-2001
      (Cohort A) and 105 between 2002-2009 (Cohort B). Overall survival increased
      significantly between 1995-2010 (P = 0.016); median survival was 365 days in
      Cohort A compared with 665 in Cohort B. The improvement in survival was
      associated with an increase in the proportion of cases detected at an
      asymptomatic stage (P = 0.012), a decline in the severity of liver disease at
      diagnosis (P = 0.002) and increased utilisation of loco-regional therapy (P =
      0.001) over the same period. Survival of patients detected through screening was
      significantly higher than those detected through non-screening methods (1309 vs
      233 days, P < 0.001). CONCLUSIONS: The survival of patients with HCC managed at a
      tertiary referral centre has improved over the period 1995-2009. This improvement
      may relate to the increased detection of the disease at an asymptomatic stage
      (e.g. through screening) as well as increased utilisation of effective loco
      regional therapies for HCC.

PMID- 22372379
TI  - Penetrative and dislodgeable residue characteristics of 14C-insecticides in apple
      fruit.
AB  - Infinite- and finite-dose laboratory experiments were used to study the
      penetrative and dislodgeable residue characteristics of (14)C-insecticides in
      apple fruit. The differences in dislodgeable and penetrated residues of three
      radiolabeled insecticides ((14)C-thiamethoxam, (14)C-thiacloprid, and (14)C
      indoxacarb), applied in aqueous solution with commercial formulations, were
      determined after water and methanol wash extractions. The rate of sorption and
      extent of penetration into the fruit cuticles and hypanthium of two apple
      cultivars were measured after 1, 6, and 24 h of treatment exposure, using
      radioactivity quantification methods. For all three compounds, 97% or more of the
      treatment solutions were found on the fruit surface as some form of non-sorbed
      residues. For indoxacarb, sorption into the epicuticle was rapid but desorption
      into the fruit hypanthium was delayed, indicative of a lipophilic penetration
      pathway. For the neonicotinoids, initial cuticular penetration was slower but
      with no such delay in desorption into the hypanthium.

PMID- 22372380
TI  - Three-year clinical follow-up of posterior teeth restored with leucite-reinforced
      ips empress onlays and partial veneer crowns.
AB  - PURPOSE: The aim of this study was to analyze the survival rate and failure mode
      of IPS leucite-reinforced ceramic onlays and partial veneer crowns regarding
      thickness under the following clinical conditions: vital versus nonvital teeth,
      tooth location, and type of opposing dentition. MATERIALS AND METHODS: Teeth were
      prepared according to established guidelines for ceramic onlays and partial
      veneer crowns. Before cementation, the restorations were measured for occlusal
      thickness at the central fossa, mesial, and distal marginal ridges, and
      functional and nonfunctional cusps. A total of 210 ceramic restorations were
      cemented in 99 patients within a mean observation period of 2.9 +/- 1.89 years.
      The mode of failure was classified and evaluated as (1) adhesive, (2) cohesive,
      (3) combined failure, (4) decementation, (5) tooth sensitivity, and (6) pulpal
      necrosis. Kaplan, log-rank, and Cox regression tests were used for statistical
      analysis. RESULTS: The failure rate was 3.33% (7/210). Increased material
      thickness produced less probability of failures. Vital teeth were less likely to
      fail than nonvital teeth. Second molars were five times more susceptible to
      failure than first molars. Tooth sensitivity postcementation and the type of
      opposing dentition were not statistically significant in this study. CONCLUSIONS:
      In this study, thickness of the restorations, tooth vitality, and location of
      teeth in the dental arch influenced restoration failures.

PMID- 22372382
TI  - Two-dimensional proteome reference map of Vibrio tapetis, the aetiological agent
      of brown ring disease in clams.
AB  - AIMS: Vibrio tapetis is the etiological agent of brown ring disease (BRD) in
      clams, one of the most threatening diseases affecting this commercially important
      bivalve. In this study we have constructed a proteome reference map of the V.
      tapetis type strain CECT 4600(T). METHODS AND RESULTS: Eighty-two proteins,
      consistently present in all 2D-gels, were identified by mass spectrometry or by
      de novo sequencing. The majority of the proteins identified (66%) belonged to
      four COG categories: 'Carbohydrate transport and metabolism', 'Post-translational
      modification, protein turnover and chaperones', 'Energy production', and 'Amino
      acid transport and metabolism'. Glyceraldehyde-3-phosphate dehydrogenase,
      enolase, fructose-bisphosphate aldolase, phosphoglycerate kinase. molecular
      chaperones Dnak and GroEL, alkyl hydroperoxide reductase, peptidyl-prolyl cis
      trans isomerase B and factor Tu, were identified among the 20 most abundant
      proteins. A comparison of this reference map with that obtained for the V.
      tapetis strain GR0202RD, with different origin and pathophysiological
      characteristics, was performed. CONCLUSIONS: Under the culture conditions
      employed in this study, glucose degradation is one of the major pathways for
      energy production in Vibrio tapetis. In addition, the two strains studied,
      although with remarkable differences at genetic and pathophysiological levels,
      showed a high similarity under laboratory conditions. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The results obtained here can be considered as a first step to gather
      valuable information on protein expression, related not only to diverse cellular
      functions and regulation but also to pathogenesis and bacterium-host interactions
      in the disease process.

PMID- 22372383
TI  - Impact of cognitive profile on social functioning in prepubescent females with
      Turner syndrome.
AB  - Social deficits are prevalent in Turner syndrome (TS); however, the extent to
      which these difficulties are secondary to characteristic cognitive impairments is
      not well known. Here, we sought to establish the relative contribution of
      executive functions, visuospatial abilities, and IQ to social difficulties in
      young girls with TS. Forty TS girls and 19 typically developing (TD) children
      were assessed with the Social Responsiveness Scale (SRS), the Motor-Free Visual
      Spatial Test (MVPT-3), the Behavior Rating Inventory of Executive Function
      (BRIEF), and an IQ test. Hierarchical multiple regression analyses were conducted
      with the SRS subscales as outcome variables. In a first step, the cognitive
      factors were entered (verbal IQ, BRIEF global score, MVPT-3, and age), followed
      by the group variable in a second step. In comparison to TD, TS participants were
      significantly impaired on all main measures. All six regression models with the
      SRS subscales were significant and revealed that global executive functions
      explained the largest portion of the variance on all subscales and the total
      score. Even after controlling for cognitive elements, the group factor still
      explained a significant portion of the variance of the Social Cognition, Social
      Awareness, and Autistic Mannerisms subscales. In contrast, the group factor was
      not a significant predictor of Social Motivation and Social Communication scores.
      These results suggest that executive dysfunctions play a role in social
      impairments encountered in TS, but also that some specific aspects of social
      behavior are altered beyond what can be attributed to cognitive difficulties in
      this population.

PMID- 22372381
TI  - Dietary agents in cancer prevention: an immunological perspective.
AB  - Skin cancer is the most common form of cancer diagnosed in the United States.
      Exposure to solar ultraviolet (UV) radiations is believed to be the primary cause
      for skin cancer. Excessive UV radiation can lead to genetic mutations and damage
      in the skin's cellular DNA that in turn can lead to skin cancer. Lately,
      chemoprevention by administering naturally occurring non-toxic dietary compounds
      has proven to be a potential strategy to prevent the occurrence of tumors.
      Attention has been drawn toward several natural dietary agents such as
      resveratrol, one of the major components found in grapes, red wines, berries and
      peanuts, proanthocyanidins from grape seeds, (-)-epigallocatechin-3-gallate from
      green tea, etc. However, the effect these dietary agents have on the immune
      system and the immunological mechanisms involved therein are still being
      explored. In this review, we shall focus on the role of key chemopreventive
      agents on various immune cells and discuss their potential as antitumor agents
      with an immunological perspective.

PMID- 22372384
TI  - Morphoscopic trait expressions used to identify Southwest Hispanics.
AB  - Hispanics represent the largest and fastest growing minority in the United
      States. It is increasingly important to understand the skeletal morphology and
      regional variation within this diverse group. This research focuses on the eight
      cranial morphoscopic traits of Southwest Hispanics from Birkby et al. (J Forensic
      Sci 2008;53(1):29-33) and 18 additional traits. Frequency distributions assessed
      the prevalence of trait expressions in Southwest Hispanic, African-American, and
      European-American samples. Forward stepwise discriminant function analysis
      indicated the best traits for differentiating these three groups. Six of the
      Birkby et al.'s traits are prevalent in the Southwest Hispanic sample and the
      best traits to distinguish the three groups are as follows: incisor shoveling,
      anterior malar projection, nasal sill, oval window visualization, enamel
      extensions, anterior nasal spine, nasal aperture width, and alveolar prognathism.
      This research demonstrates the efficacy of morphoscopic traits in ancestry
      determinations and the utility of the aforementioned traits in discriminating
      Southwest Hispanics, African Americans, and European Americans.

PMID- 22372385
TI  - Management of abnormal serum markers in the absence of aneuploidy or neural tube
      defects.
AB  - OBJECTIVE: Few guidelines address the management of pregnancies complicated by
      abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural
      tube defects (NTDs). Our objective was to gather preliminary data regarding
      current opinions and management strategies among perinatologists in the US.
      METHODS: This survey of Maternal Fetal Medicine (MFM) physicians and fellows used
      a secure electronic web-based data capture tool. RESULTS: A total of 545
      potential participants were contacted, and 136 (25%) responded. The majority were
      experienced academic physicians with robust practices. Nearly all (97.7%)
      respondents reported a belief in an association between abnormal MSAs and adverse
      pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and
      alpha-fetoprotein (AFP) were most often chosen as markers demonstrating a strong
      association with adverse outcomes. Most (86.9%) respondents acknowledged that
      abnormal MSAs influenced their counseling approach, and the majority (80.1%)
      offered additional ultrasound examinations. Nearly half started at 28 weeks and
      almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in
      their hospital or practice were more likely to offer additional antenatal testing
      (p = 0.01). CONCLUSIONS: Although most perinatologists were in agreement
      regarding the association of MSAs with adverse pregnancy outcomes, a lack of
      consensus exists regarding management strategies.

PMID- 22372386
TI  - Split-face comparative study of 1550 nm fractional photothermolysis and
      trichloroacetic acid 15% chemical peeling for facial melasma in Asian skin.
AB  - Fractional photothermolysis (FP) therapy and chemical peels have been reported to
      be effective in patients with recalcitrant melasma. However, there is little
      information to compare the efficacy of single treatment session in Asian women.
      The aim of this study was to examine the efficacy, long-lasting outcomes and
      safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared
      with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women
      (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were
      randomly treated with a single session of 1550-nm FP on one cheek, and with a 15%
      TCA peel on the other cheek. Outcome measures included an objective melasma area
      severity index and subjective patient-rated overall improvement at 4 and 12 weeks
      after treatment. Melasma lesions were significantly improved 4 weeks after either
      treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation
      developed in 28% of patients at 4 weeks but resolved in all but one patient by 12
      weeks. There was no difference between FP treatment and TCA peeling with respect
      to any outcome measure. FP laser and TCA peel treatments were equally effective
      and safe when used to treat moderate-to-severe melasma, but neither treatment was
      long-lasting. We suggest that multiple or periodic maintenance treatments and/or
      supplemental procedures may be required for the successful treatment of melasma
      in Asian women.

PMID- 22372387
TI  - Palladium-catalyzed intramolecular hydroarylation of 4-benzofuranyl alkynoates.
      Approach to angelicin derivatives.
AB  - Intramolecular hydroarylation of 4-benzofuranyl alkynoates using Pd(OAc)(2) as
      catalyst took place selectively and efficiently, giving angular furocoumarin
      derivatives in high yields. The parent angelicin was obtained in 80% yield by
      this method. The starting 4-benzofuranyl alkynoates were easily accessible from
      readily available 4-hydroxybenzofurans and alkynoic acids.

PMID- 22372388
TI  - Student diversity and implications for clinical competency development amongst
      domestic and international speech-language pathology students.
AB  - International students graduating from speech-language pathology university
      courses must achieve the same minimum competency standards as domestic students.
      This study aimed to collect descriptive information about the number, origin, and
      placement performance of international students as well as perceptions of the
      performance of international students on placement. University Clinical Education
      Coordinators (CECs), who manage clinical placements in eight undergraduate and
      six graduate entry programs across the 10 participating universities in Australia
      and New Zealand completed a survey about 3455 international and domestic speech
      language pathology students. Survey responses were analysed quantitatively and
      qualitatively with non-parametric statistics and thematic analysis. Results
      indicated that international students came from a variety of countries, but with
      a regional focus on the countries of Central and Southern Asia. Although domestic
      students were noted to experience significantly less placement failure, fewer
      supplementary placements, and reduced additional placement support than
      international students, the effect size of these relationships was consistently
      small and therefore weak. CECs rated international students as more frequently
      experiencing difficulties with communication competencies on placement. However,
      CECs qualitative comments revealed that culturally and linguistically diverse
      (CALD) students may experience more difficulties with speech-language pathology
      competency development than international students. Students' CALD status should
      be included in future investigations of factors influencing speech-language
      pathology competency development.

PMID- 22372389
TI  - Risk factors for superficial digital flexor tendinopathy in Thoroughbred
      racehorses in hurdle starts in the UK (2001-2009).
AB  - REASONS FOR PERFORMING STUDY: Superficial digital flexor (SDF) tendinopathy is a
      common injury in Thoroughbred horses racing over hurdles. Identification of risk
      factors may allow the introduction of measures to minimise the incidence of this
      injury. OBJECTIVE: To identify risk factors for SDF tendinopathy in Thoroughbred
      horses in hurdle races in the UK. METHODS: Potential risk factors for SDF
      tendinopathy were studied between 1 January 2001 and 31 December 2009 using a
      retrospective cohort study design with 1031 case starts and 168,637 control
      starts. Potential risk factors were screened using univariable logistic
      regression prior to multivariable model building. RESULTS: IN the final
      multivariable model, 20 statistically significant risk factors were identified.
      Variables found to be associated with increased odds of SDF tendinopathy
      included: firmer going; increased horse age at first race; having had a previous
      SDFT injury; and racing in the summer compared to other seasons. Variables found
      to be associated with decreased odds included: being trained by a more successful
      trainer; and having raced more frequently in the preceding 9-12 months.
      CONCLUSIONS: This study identified multiple risk factors associated with SDF
      tendinopathy, some of which are difficult to explain with the current data
      source. Factors resulting in increased cumulative horse and tendon fatigue
      (increased years in racing; carrying increased weight; and racing over longer
      distances), firm ground, and the presence of previous tendon injury should be
      considered when attempting to reduce the likelihood of sustaining SDF
      tendinopathy. POTENTIAL RELEVANCE: The results will facilitate the development of
      strategies to improve the overall safety of horses in hurdle racing in the UK.

PMID- 22372390
TI  - MicroRNAs as components of regulatory networks controlling erythropoiesis.
AB  - Over the last two decades, the role of microRNAs has been extensively
      investigated, and it has become clear that these small non-coding RNAs play an
      essential role in several biological processes including erythropoiesis and that
      their dysregulation is associated with pathologies. Recent technical innovations
      have considerably advanced this field and allowed extensive study of microRNA
      expression and regulation in a variety of cell types. In erythropoiesis, microRNA
      regulation is involved at defined stages and promotes either stem cell
      proliferation or erythroid cell differentiation. In this review, while
      recapitulating the maturation steps of erythroid cells, we discuss the progresses
      in our understanding of microRNA regulation in the erythroid lineage and their
      contribution to erythroid disorders.

PMID- 22372391
TI  - Strengthening the science of forensic nursing through education and research.

PMID- 22372393
TI  - An evolutionary concept analysis of school violence: from bullying to death.
AB  - School violence has evolved into an identifiably pervasive public health problem.
      Adverse consequences of school violence vary from bullying to death. In 2007,
      457,700 youth (ages 12-18) were victims of serious crimes with 34% occurring on
      school grounds or on the way to school. A concept analysis of school violence can
      expand and enhance awareness of the pervasive phenomenon of school violence.
      Rodgers and Knafl (1993) evolutionary concept analysis method was used to provide
      a guiding framework for examination of school violence. Related manuscripts from
      the extant interdisciplinary school violence literature were obtained from
      relevant health science databases, the Education Resources Information Center,
      and various governmental and specialty websites within the contemporary time
      frame of 2000-2010. Analysis revealed the enormous scope and complexity of the
      problem of school violence including bullying, physical fighting, weapon
      carrying, alcohol/substance use and street gang presence on school property,
      school-associated violent death, safe schools legislation, and violence
      prevention strategies. Forensic nurses across practice settings are uniquely
      positioned to intervene to improve health of these youth through identification,
      assessment, treatment, and referral.

PMID- 22372395
TI  - Temperament, insecure attachment, impulsivity, and sexuality in women in jail.
AB  - BACKGROUND: Women constitute only a small proportion of inmates, but several
      studies have shown that they have higher rates of psychiatric disturbance than
      incarcerated men and community samples. Mental health treatment is necessary to
      prevent severe illness and suicide in these women. METHODS: The convenience
      sample consisted of 40 female detainees and 40 controls who were administered
      self-report questionnaires to assess temperament (TEMPS-A), insecure attachment
      (ECR), impulsivity (BIS-11), and sexual behavior (SESAMO). RESULTS: The
      incarcerated women had higher levels of affective temperament (except for
      hyperthymia), avoidance, anxiety, impulsivity, and psychosexual issues than the
      female community sample. CONCLUSIONS: Many interrelated emotional and affective
      disturbances affect the physical and psychological well-being of women in jail,
      and it is possible that these problems may lead to suicide. Health professionals
      need to develop gender-specific therapeutic interventions for women in jail.

PMID- 22372394
TI  - Hepatitis A/B vaccine completion among homeless adults with history of
      incarceration.
AB  - Hepatitis B virus (HBV) vaccination rates for incarcerated adults remain low
      despite their high risk for infection. This study determined predictors of
      vaccine completion in homeless adults (N= 297) who reported histories of
      incarceration and who participated in one of three nurse-led hepatitis programs
      of different intensity. Moreover time since release from incarceration was also
      considered. Just over half of the former prisoners completed the vaccine series.
      Older age (>=40), having a partner, and chronic homelessness were associated with
      vaccine completion. Recent research has documented the difficulty in providing
      vaccine services to younger homeless persons and homeless males at risk for HBV.
      Additional strategies are needed to achieve HBV vaccination completion rates
      greater than 50% for formerly incarcerated homeless men.

PMID- 22372396
TI  - A pilot study to test the differential validity of a genital injury severity
      scale, in development for use in forensic sexual assault examinations.
AB  - Methods of examining the sexual assault patient are not standardized and a
      definition of what constitutes significant genital injury after sexual assault
      (SA) remains controversial. This pilot study tests the empirical validity
      (initial differential validity) of a genital injury severity scale (GISS) under
      development by the authors with the hypothesis that women who report SA have more
      severe external genital injuries than those who engage in consensual intercourse
      (CI). In this observational, prospective study, an initially developed GISS is
      applied and the exam results of 59 CI volunteers and 185 SA patients are
      compared. All examinations were performed by experienced sexual assault forensic
      examiners (SAFE) using toluidine blue (TB) and colposcopy. The Independent
      Samples Median Test indicates a significant difference in median genital injury
      type between CI and SA subjects (p < 0.0001). There is a significant difference
      in the prevalence of Class A (less severe) and Class B injuries (more severe)
      between the SA and the CI groups (SA: Class A 60%/Class B 40%; CI: Class A
      90%/Class B 10% (p= 0.0001)). This initial validation study shows effectiveness
      in using magnification and TB, combined with a standardized injury severity
      scale, in describing external genital injury in women after sexual intercourse.

PMID- 22372397
TI  - Alternate light sources in sexual assault examinations: an evidence-based
      practice project.
AB  - The ability of sexual assault nurse examiners to correctly identify and collect
      DNA evidence improves patient outcomes and prosecution rates. The purpose of this
      paper is to present findings from a collaborative evidence-based practice (EBP)
      project between forensic nurses and baccalaureate nursing students. The goal of
      the project was to determine best practice using an alternate light source (ALS)
      to identify trace DNA evidence in sexual assault forensic examinations. Using the
      Johns Hopkins Nursing Evidence-based Practice model, the team searched several
      databases to summarize the limited amount of evidence available regarding this
      topic. Recommendations from the EBP project include: elimination of the Wood's
      lamp in sexual assault examinations; use of an ALS that provides appropriate
      wavelengths to detect DNA; education of forensic nurses about the advantages and
      limitations of an ALS; and additional research related to use of an ALS. By
      participating in similar collaborative efforts, practicing forensic nurses have
      the opportunity to collaborate with local colleges and universities to make
      complex projects more manageable while fulfilling the International Association
      of Forensic Nurses vision for ethical practice.

PMID- 22372398
TI  - Forensic anthropology casework-essential methodological considerations in stature
      estimation.
AB  - The examination of skeletal remains is a challenge to the medical
      examiner's/coroner's office and the forensic anthropologist conducting the
      investigation. One of the objectives of the medico-legal investigation is to
      estimate stature or height from various skeletal remains and body parts brought
      for examination. Various skeletal remains and body parts bear a positive and
      linear correlation with stature and have been successfully used for stature
      estimation. This concept is utilized in estimation of stature in forensic
      anthropology casework in mass disasters and other forensic examinations.
      Scientists have long been involved in standardizing the anthropological data with
      respect to various populations of the world. This review deals with some
      essential methodological issues that need to be addressed in research related to
      estimation of stature in forensic examinations. These issues have direct
      relevance in the identification of commingled or unknown remains and therefore it
      is essential that forensic nurses are familiar with the theories and techniques
      used in forensic anthropology.

PMID- 22372400
TI  - Editorial comment. Evolving practice patterns for the management of small renal
      masses in the USA.

PMID- 22372401
TI  - Increased expression of ZBP-89 and its prognostic significance in hepatocellular
      carcinoma.
AB  - AIMS:   ZBP-89 plays a role in cell growth and death. Its expression in
      hepatocellular carcinoma (HCC) is not well documented. This study aimed to
      analyse ZBP-89 expression in HCC. METHODS AND RESULTS:   We examined ZBP-89
      expression in five HCC cell lines and 182 HCC tissue samples by reverse
      transcription-polymerase chain reaction (RT-PCR), Western blot analysis and
      immunofluorescence staining. Our results showed that the expression of ZBP-89 was
      higher in HCC than adjacent non-tumour liver, at both mRNA and protein levels.
      ZBP-89 was localized in the nucleus in most HCC tissue samples, but was found in
      the cytoplasm in 11.5% of cases. Patient survival in those tumours showing high
      ZBP-89 expression was better than in those with low expression. High ZBP-89
      expression tended to be more common in World Health Organization (WHO) grade I
      than grades II-IV HCC. There was a significant association between HBV positivity
      and high ZBP-89 expression. Colony formation was reduced dramatically in those
      HCC cell lines in which ZBP-89 overexpression was demonstrated; this appeared to
      correlate with increased apoptosis, inferred by finding elevated levels of
      cleaved poly(ADP-ribose)polymerases (PARP), the probable mechanisms for which may
      involve increased p53 or p21 expression. CONCLUSIONS:   ZBP-89 has anti-tumour
      properties and is a potential biomarker for prognosis of HCC.

PMID- 22372402
TI  - An octanuclear molybdenum(VI) complex containing coordinatively bound 4,4'-di
      tert-butyl-2,2'-bipyridine, [Mo8O22(OH)4(di-tBu-bipy)4]: synthesis, structure,
      and catalytic epoxidation of bio-derived olefins.
AB  - The reaction of [MoO(2)Cl(2)(di-tBu-bipy)] (1) (di-tBu-bipy = 4,4'-di-tert-butyl
      2,2'-bipyridine) with water at 100-120  degrees C in a Teflon-lined stainless
      steel autoclave, in an open reflux system, or in a microwave synthesis system
      gave the octanuclear complex [Mo(8)O(22)(OH)(4)(di-tBu-bipy)(4)] (2) as a
      microcrystalline powder in good yields. Single crystals of 2 suitable for X-ray
      diffraction were obtained by the reaction of MoO(3) and di-tBu-bipy in water at
      160  degrees C for 3 days. The molecular structure of 2 comprises a purely
      inorganic core, Mo(4)O(8)(MU(3)-OH)(2)(MU(2)-O)(2), attached to two peripheral
      oxo-bridged binuclear units, Mo(2)O(4)(MU(2)-O)(2)(OH)(di-tBu-bipy)(2). The
      inorganic core is composed of a unique assembly of four {MoO(5)} distorted square
      pyramids connected to each other via edge-sharing. Overall, the octanuclear
      complex adopts a highly distorted form strongly resembling an "S"-shaped
      molecular unit. Complex 2 was applied in the catalytic epoxidation of the
      biorenewable olefins DL-limonene (Lim) and methyl oleate (Ole), using tert
      butylhydroperoxide (TBHP) as an oxygen donor, under mild reaction conditions (55 
      degrees C, air). The reactions of Lim and Ole gave the respective epoxide
      monomers in fairly high selectivities at high conversions (89% 1,2-epoxy-p-menth
      8-ene selectivity at 96% Lim conversion; 99% methyl 9,10-epoxystearate
      selectivity at 94% Ole conversion, reached within 24 h reaction). Iodometric
      titrations revealed no measurable "non-productive" decomposition of TBHP.

PMID- 22372403
TI  - Guest-to-host transmission of structural changes for stimuli-responsive
      adsorption property.
AB  - We show that structural changes of a guest molecule can trigger structural
      transformations of a crystalline host framework. Azobenzene was introduced into a
      flexible porous coordination polymer (PCP), and cis/trans isomerizations of the
      guest azobenzene by light or heat successfully induced structural transformations
      of the host PCP in a reversible fashion. This guest-to-host structural
      transmission resulted in drastic changes in the gas adsorption property of the
      host-guest composite, displaying a new strategy for creating stimuli-responsive
      porous materials.

PMID- 22372404
TI  - Improving the stability of nanostructured silicon thin film lithium-ion battery
      anodes through their controlled oxidation.
AB  - Silicon and partially oxidized silicon thin films with nanocolumnar morphology
      were synthesized by evaporative deposition at a glancing angle, and their
      performance as lithium-ion battery anodes was evaluated. The incorporated oxygen
      concentration was controlled by varying the partial pressure of water during the
      deposition and monitored by quartz crystal microbalance, X-ray photoelectron
      spectroscopy. In addition to bulk oxygen content, surface oxidation and annealing
      at low temperature affected the cycling stability and lithium-storage capacity of
      the films. By simultaneously optimizing all three, films of ~2200 mAh/g capacity
      were synthesized. Coin cells made with the optimized films were reversibly cycled
      for ~120 cycles with virtually no capacity fade. After 300 cycles, 80% of the
      initial reversible capacity was retained.

PMID- 22372405
TI  - Impact of short-term intake of red wine and grape polyphenol extract on the human
      metabolome.
AB  - Red wine and grape polyphenols are considered to promote cardiovascular health
      and are involved in multiple biological functions. Their overall impact on the
      human metabolome is not known. Therefore, exogenous and endogenous metabolic
      effects were determined in fasting plasma and 24 h urine from healthy male adults
      consuming a mix of red wine and grape juice extracts (WGM) for 4 days in a
      placebo-controlled, crossover study. Syringic acid, 3-hydroxyhippuric acid,
      pyrogallol, 3-hydroxyphenylacetic acid, and 3-hydroxyphenylpropionic acid were
      confirmed as the strongest urinary markers of WGM intake. Overall, WGM had a mild
      impact on the endogenous metabolism. Most noticeable were changes in several
      amino acids deriving from tyrosine and tryptophan. Reductions in the microbial
      metabolites p-cresol sulfate and 3-indoxylsulfuric acid and increases in indole-3
      lactic acid and nicotinic acid were observed in urine. In plasma, tyrosine was
      reduced. The results suggest that short-term intake of WGM altered microbial
      protein fermentation and/or amino acid metabolism.

PMID- 22372406
TI  - Nonequilibrium isotope exchange reveals a catalytically significant enzyme
      phosphate complex in the ATP hydrolysis pathway of the AAA(+) ATPase magnesium
      chelatase.
AB  - Magnesium chelatase is an AAA(+) ATPase that catalyzes the first committed step
      in chlorophyll biosynthesis. Using nonequilibrium isotope exchange, we show that
      the ATP hydrolysis reaction proceeds via an enzyme-phosphate complex. Exchange
      from radiolabeled phosphate to ATP was not observed, offering no support for an
      enzyme-ADP complex.

PMID- 22372408
TI  - Diffusion tensor imaging and volumetric analysis of the ventral striatum in
      adults with traumatic brain injury.
AB  - OBJECTIVES: The aim was to determine if there are changes in the integrity and
      volume of the ventral striatum following severe traumatic brain injury (TBI) and
      if these changes relate to executive functioning. METHODS: This study recruited
      14 participants with severe TBI (mean age: 22 years) and 15 demographically
      matched controls. All participants underwent magnetic resonance imaging with
      diffusion tensor imaging (DTI) and volumetric analysis at 6 months post-injury.
      Participants with TBI underwent neuropsychological testing and the relation
      between imaging data and cognitive performance was examined. RESULTS: Differences
      in DTI parameters (fractional anisotropy (FA) and apparent diffusion coefficient
      (ADC)) were found between participants with TBI and controls. Correlations
      between right and left ventral striatum ADC and the executive functioning factor
      of the Neurobehavioural Rating Scale-Revised (NRS-R) were found. Correlations
      between right ventral striatum FA and the Controlled Oral Word Association Test,
      Trails Making Test Part B (TMT-B) time and NRS-R executive functioning factor
      were also found. Volumetric analysis showed a difference only in left nucleus
      accumbens between TBI and control groups. CONCLUSIONS: The integrity of the
      ventral striatum is affected following severe TBI. Decreases in executive
      functioning are related to damage to the ventral striatum and its associated
      structures.

PMID- 22372409
TI  - Neuropsychological and neurophysiological assessment of sport concussion in
      children, adolescents and adults.
AB  - OBJECTIVE: To determine whether age differences exist with respect to
      neuropsychological and electrophysiological functioning following a sport
      concussion. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-six athletes (9
      12 years, n = 32; 13-16 years, n = 34; adults, n = 30), half of whom had a sport
      concussion. INTERVENTION: Cognitive functioning was assessed using standardized
      neuropsychological tests and event-related potentials elicited by a visual 3
      stimulus oddball paradigm. The PCSS was used to assess symptoms experienced at
      the time of injury. MAIN OUTCOME MEASUREMENTS: Neuropsychological assessment with
      an adaptation of the battery used by the National Hockey League. Latencies and
      amplitudes of the P3a and P3b were analysed in terms of group (concussed vs.
      control) and age. RESULTS: All concussed athletes had significantly lower
      amplitude for the P3b component compared to their non-injured teammates (p >
      0.05). Adolescents also showed persistent deficits in working memory (p > 0.05).
      CONCLUSIONS: These data suggest persistent neurophysiological deficits that are
      present at least 6 months following a concussion. Moreover, adolescents are more
      sensitive to the consequences of concussions than are children or adults.

PMID- 22372410
TI  - Casual conversations between individuals with traumatic brain injury and their
      friends.
AB  - PRIMARY OBJECTIVE: To investigate casual conversations with friends following
      severe traumatic brain injury (TBI). METHODS: Nine participants with severe TBI
      were matched by age, gender and education to nine control participants. Each
      participant also invited a friend to partake in the study. Participants were
      recorded engaging in a brief casual conversation with a friend. The resulting
      discourse was analysed using Exchange Structure Analysis (ESA). Rates of
      information giving, information requesting and communication repair and
      negotiation were collated. Non-parametric statistical analyses were performed.
      RESULTS: Participants with and without TBI obtained similar rates of information
      giving and information requesting. The friends of the participants with TBI
      produced significantly lower rates of information giving measures when compared
      to the controls, but achieved comparable rates of information requesting and
      communication repair and negotiation measures. Participants with TBI were
      observed to produce tangential language and to have difficulties identifying
      communication breakdown, asking questions and engaging in conversational joking.
      CONCLUSIONS: People with TBI are able to engage in casual conversations with
      friends in a similar way to matched controls. Friends of people with TBI are
      often restricted in contributing information in conversations. Further research
      is needed to specify the facilitative and restrictive communication behaviours so
      that they may be translated to clinical practise.

PMID- 22372411
TI  - A comparison of two assessments of high level cognitive communication disorders
      in mild traumatic brain injury.
AB  - PRIMARY OBJECTIVES: Individuals with traumatic brain injury (TBI) frequently
      encounter cognitive communication disorders. Deficits can be subtle but can
      seriously influence an individual's ability to achieve life goals. Feedback from
      rehabilitation facilities indicated that high level cognitive communication
      disorders are not consistently identified in the acute setting. This study aimed
      to compare the cognitive communication results from two screening assessments,
      the Cognistat and the Cognitive Linguistic Quick Test (CLQT), in participants
      with a mild traumatic brain injury and to relate these findings to a range of
      prognostic indicators. METHODS: Eighty-three adults post-TBI (16-81 years; 79.5%
      males) were recruited at an acute trauma centre. The language components of the
      two tests were analysed. MAIN OUTCOMES AND RESULTS: The CLQT identified more
      participants with an impairment in language than the Cognistat, 19.3% compared to
      1.2% (p < 0.001). No clinical variables relating to the participants' brain
      injury were found to be associated with language impairment. CONCLUSIONS: This
      study found that the CLQT identified more individuals with high level cognitive
      communication deficits than the Cognistat in the acute setting.

PMID- 22372412
TI  - Effect of speech rate manipulations on articulatory dynamics in severe traumatic
      brain injury: an EMA and EPG study.
AB  - BACKGROUND: Manipulation of speech rate forms an integral part of the treatment
      of dysarthria and the effects of changes in speech rate on articulatory dynamics
      in persons with traumatic brain injury (TBI) is poorly documented. OBJECTIVE: To
      determine the effects of manipulations of speech rate (habitual vs fast) on
      lingual kinematics and tongue-to-palate contacts in adult speakers with severe
      TBI and matched normal controls. MATERIALS AND METHODS: Six adults with severe
      TBI and five matched non-neurologically impaired controls underwent testing of
      their articulatory function using electromagnetic articulography (EMA) and
      electropalatography (EPG). RESULTS: The results demonstrated that the TBI and
      control groups selected different strategies for increasing speech rate, with the
      TBI group showing an increase in articulatory effort estimated from an increase
      in maximum velocity and maximum acceleration/deceleration of tongue movement when
      speaking at the fast rate. The control group demonstrated no effects of a fast
      speech rate on articulatory kinematics for sentence productions. CONCLUSIONS:
      When speaking at a fast rate, individuals with severe TBI appear to use greater
      articulatory effort, possibly to preserve the distinctiveness of phonetic
      segments in order to avoid articulatory undershoot. In contrast, control subjects
      show a greater economy of effort when speaking at a fast rate, possibly to
      preserve articulatory precision.

PMID- 22372413
TI  - Associations between disability and employment 1 year after traumatic brain
      injury in a working age population.
AB  - OBJECTIVE: To investigate associations between disability and employment 1 year
      after traumatic brain injury (TBI) using the International Classification of
      Functioning, Disability and Health (ICF) as a conceptual model. DESIGN AND
      METHODS: A prospective study including 93 patients with moderate-to-severe TBI
      (aged 16-55 year). Disability components of the ICF model (impairments, activity
      limitations and participation restrictions) and personal factors (age, gender,
      pre-injury employment status) were used as independent variables. The outcome
      measure was employment at 1 year post-injury categorized into unemployed and
      employed groups. RESULTS: Personal factors, impairments (brain injury severity,
      overall trauma severity and number of impaired body functions) and activity
      limitations (motor and cognitive abilities) accounted for 57% of the variance in
      employment outcome. Multivariate analyses showed that the probabilities of being
      employed 1 year post-injury were 95% lower for patients who were unemployed pre
      injury (OR = 0.05), 74% lower for those with more severe brain injury (OR = 0.26)
      and 82% lower for those with more cognitive limitations (OR = 0.18). CONCLUSION:
      Rehabilitation professionals should take into account the importance of the ICF
      model when planning vocational rehabilitation interventions for individuals with
      TBI and focus on targeting modifiable aspects related to employment outcome, such
      as the individual's cognitive ability.

PMID- 22372414
TI  - Quality-of-life, mood and executive functioning after childhood craniopharyngioma
      treated with surgery and proton beam therapy.
AB  - PRIMARY OBJECTIVE: Childhood craniopharyngioma, a benign tumour with a good
      survival rate, is associated with important neurocognitive and psychological
      morbidity, reducing quality-of-life (QoL). METHOD: This retrospective study
      analysed QoL, mood disorders, everyday executive functioning and disease's impact
      on family life in 29 patients (mean age at diagnosis 7 years 10 months (SD =
      4.1); mean follow-up period 6 years 2 months (SD = 4.5)) treated for childhood
      craniopharyngioma by surgery combined with radiotherapy using proton beam.
      Assessment included a semi-structured interview and standardized scales
      evaluating self-report of QoL (Kidscreen 52) and depression (MDI-C) and proxy
      reports of QoL (Kidscreen 52), executive functioning (BRIEF) and disease's impact
      (Hoare and Russel Questionnaire). RESULTS: Twenty-three families answered the
      questionnaires completely. Overall QoL self-report was within the normal range.
      QoL proxy-report was lower than self-report. Eleven patients reported depression;
      24-38% had dysexecutive symptoms. A majority of families felt 'very concerned' by
      the disease. Depression and low parental educational level were associated with
      lower QoL and higher levels of executive dysfunction. CONCLUSION: Given the high
      morbidity of childhood craniopharyngioma, screening for psychosocial outcome,
      cognitive functioning, including executive functions, mood and QoL should be
      systematic and specific interventions should be developed and implemented.

PMID- 22372415
TI  - Effect of hypobaric hypoxia on the P2X receptors of pyramidal cells in the
      immature rat hippocampus CA1 sub-field.
AB  - PRIMARY OBJECTIVE: This study was designed to evaluate the effect of hypobaric
      hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus
      CA1 pyramidal cells. RESEARCH DESIGN: The functional changes of P2X receptors
      were investigated through the cell HH model and the expressional alterations of
      P2X receptors were observed through the animal HH model. METHODS AND PROCEDURE:
      P2X receptors mediated currents were recorded from the freshly dissociated CA1
      pyramidal cells of 7-day-old SD rats by whole cell patch clamp recording. The
      expression and distribution of P2X receptors were observed through
      immunohistochemistry and western blot at HH 3-day and 7-day. MAIN OUTCOMES AND
      RESULTS: In acute HH conditions, the amplitudes of ATP evoked peak currents were
      decreased compared to control. The immunohistochemistry and western blot results
      reflected there was no change in P2X receptors expression after 3 days HH injury,
      while P2X receptors expression was up-regulated in response to 7 days HH injury.
      CONCLUSIONS: These findings supported the possibility that the function of P2X
      receptors was sensitive to HH damage and long-term function decrease should
      result in the expression increase of P2X receptors.

PMID- 22372416
TI  - Prognostic relevance of circulating endothelial progenitor cells for severe
      traumatic brain injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) promotes the recruitment of endothelial
      progenitor cells (EPCs) into the injured tissue where EPCs play an important role
      in repairing injured vasculature. However, the repair mechanism and prognostic
      significance of EPCs after TBI remain poorly understood. METHODS: Blood samples
      were collected from 21 patients with severe TBI and 20 healthy subjects. EPCs
      were quantified by flow cytometry and serum VEGF and MMP-9 level measured by
      ELISA on days 1, 4, 7, 14 and 21 after TBI. RESULTS: EPCs in the patients
      decreased originally, then increased to the peak level at 7 days and was
      significantly correlated with GOS scores 6 months after TBI. VEGF and MMP-9 were
      significantly increased during the follow-up period after TBI. EPCs was also
      positively correlated with GCS score 1 day after TBI and with MMP-9 and VEGF 7
      days and 14 days after TBI. CONCLUSION: The data demonstrate that TBI led to an
      increase of EPCs, VEGF and MMP-9, suggesting that increased VEGF and MMP-9 may
      mediate the recruitment of bone marrow-derived EPCs into the circulation. The
      association of EPCs with nerve functional recovery in patients provides evidence
      that EPCs may be a potential biomarker to monitor TBI angiogenesis and prognosis.

PMID- 22372417
TI  - Long-term cognitive complaint and post-concussive symptoms following mild
      traumatic brain injury: the role of cognitive and affective factors.
AB  - PRIMARY OBJECTIVE: To determine whether neuropsychological test performance or
      affective factors predict long-term post-concussive symptoms and cognitive
      complaint following mild traumatic brain injury. METHODS AND PROCEDURES:
      Participants included 21 individuals with mild traumatic brain injury, 19
      individuals with spinal injury but no injury to the brain and 20 neurologically
      normal controls. All participants completed measures of post-concussive symptoms,
      cognitive complaint, depression, anxiety, and personality and were administered a
      variety of neuropsychological tests. MAIN OUTCOMES AND RESULTS: The hypothesis
      that depression, anxiety and neuroticism would be better predictors of post
      concussive symptoms than neuropsychological test performance for all three groups
      was supported. Contrary to expectations, however, neuropsychological test
      performance was a unique predictor of cognitive complaint for the mild traumatic
      brain injury group. CONCLUSIONS: It was concluded that long-term post-concussive
      symptoms are largely representative of psychological symptoms and not brain
      damage, but that genuine, albeit subtle, cognitive deficits also may be present
      for long-term periods following mild traumatic brain injury.

PMID- 22372418
TI  - Laser-assisted lipolysis for knee remodelling: a prospective study in 30
      patients.
AB  - BACKGROUND: Unsightly fat knees are a frustrating aesthetic deformity exacerbated
      by genetic predisposition and resistance to diet. This article reports our
      experience with laser-assisted lipolysis (LAL) in knee remodelling. METHODS: A
      total of 30 patients were treated for unsightly fat knees with LAL. The 924/975
      nm diode laser used in this study consists of two lasers, one emitting at 924 nm
      and another at 975 nm. Previous mathematical modelling suggested that 0.1 kJ was
      required in order to destroy 1 ml of fat, in dual emission mode at 924/975 nm.
      Patients were asked to fill out a satisfaction questionnaire. Ultrasound was used
      to measure the fat thickness pre-and post-operatively. RESULTS: Other than one
      patient who developed mild hyperpigmentation that disappeared after 2 months,
      there were no complications in the series. Pain during the anaesthesia and
      discomfort after the procedure were minimal. Return to normal activities never
      took longer than 2 days and mean downtime was 0.92 days. Of the 30 patients, 29
      would recommend this treatment. Overall satisfaction was high with both patients
      and investigators and was validated by ultrasound measurements demonstrating a
      systematic decrease in fat thickness. CONCLUSION: LAL in knee remodelling is a
      safe and reproducible technique, particularly appreciated by patients. The
      procedure allows for a reduction in the amount of adipose deposits while
      providing concurrent skin contraction.

PMID- 22372419
TI  - Intramolecular aminoalkene hydroamination mediated by a tethered
      bis(ureate)zirconium complex: computational perusal of various pathways for
      aminoalkene activation.
AB  - The present study comprehensively explores alternative mechanistic pathways for
      the intramolecular hydroamination of the prototype 2,2-dimethyl-5-penten-1-amine
      aminoalkene (1) by bis(ureate)Zr(IV)(NMe(2))(2)(HNMe(2)) (2), which proceeds
      through a Zr(IV)(NHR)(2) intermediate using density functional theory (DFT)
      calculations. The classical stepwise sigma-insertive mechanism that includes
      insertion of the C?C double bond into the Zr-N amido sigma bond followed by Zr-C
      alkyl-bond aminolysis has been compared with a single-step pathway for
      amidoalkene -> cycloamine conversion through a concerted amino proton transfer
      associated with N-C ring closure. Noncompetitive kinetics for reversible sigma
      insertive cyclization, together with the incompatibility of a turnover-limiting
      insertion step with observed pronounced primary kinetic isotope effects (KIEs),
      strongly militates against the operation of a sigma-insertive mechanism. A
      noninsertive pathway evolving through an ordered six-center transition-state
      structure describing N-C bond formation at an axial Zr-N amido sigma bond
      triggered by concurrent proton transfer from an equatorially bound substrate
      molecule onto the adjacent olefin-carbon center is found to prevail
      energetically. The proton-triggered noninsertive cyclization commencing from a
      catalytically relevant Zr(IV)(NHR)(2)(NH(2)R) substrate adduct is strongly
      downhill, followed by product expulsion via dissociative amine exchange. The
      assessed effective barrier compares reasonably well with the previously
      determined Eyring parameters, and the computationally estimated primary KIEs
      match the observed values pleasingly well. The present study reveals a comparable
      strength of substrate and product binding in relevant seven-coordinate
      intermediates, together with a rapid equilibrium between related primary and
      secondary amido species, which favors the former, as unique features of the
      studied catalyst. Thus, in line with experimental observations, competitive
      product inhibition can be discarded. On the basis of all of these findings, it is
      suggested that a Zr(NHR)(2)(substrate) intermediate corresponds to the catalyst
      resting state at high substrate concentrations, while it becomes a
      Zr(NHR)(2)(cycloamine) species when the product concentration is high or with the
      addition of excess 2-methylpiperidine, and this ambivalent behavior explains the
      observed operation of two distinct kinetic regimes, depending upon the extent of
      the reaction.

PMID- 22372420
TI  - Prevalence of traumatic brain injury in juvenile offenders: a meta-analysis.
AB  - Studies of traumatic brain injury (TBI) among adult populations demonstrate that
      such injuries can lead to aggressive behaviors. Related findings suggest that
      incarcerated individuals have high rates of brain injuries. Such studies suggest
      that traumatic brain injury may be related to the etiology and recidivism of
      criminal behavior. Relatively few studies have examined the prevalence of TBI
      using a delinquent juvenile sample. In order to assess the relationship between
      TBI and juvenile offender status, the current study used meta-analytic techniques
      to examine the odds of having a TBI among juvenile offenders. Across 9 studies,
      we found that approximately 30% of juvenile offenders have sustained a previous
      brain injury. Across 5 studies that used a control group, a calculated summary
      odds ratio of 3.37 suggests that juvenile offenders are significantly more likely
      to have a TBI compared to controls. Results suggest that the rate of TBIs within
      the juvenile offender population is significant and that there may be a
      relationship between TBIs and juvenile criminal behavior.

PMID- 22372421
TI  - Pre-induction of labour: comparing dinoprostone vaginal insert to repeated
      prostaglandin administration: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the efficacy and safety of the dinoprostone vaginal insert
      compared to repeated prostaglandin administration (including dinoprostone and
      misoprostol) in women at term. METHODS: Electronic databases and additional
      handsearching were used to identify randomized controlled trial (RCT). We
      included studies reporting data separately for nulliparous and/or multiparous in
      women with unfavourable cervix (Bishop <5) and intact membranes. The primary
      efficacy outcome was caesarean section (CS) rate. Primary safety outcome was
      uterine hyperstimulation requiring immediate delivery. RESULTS: Eighteen RCTs
      were eligible and seven studies were included (totally 911 patients). The
      dinoprostone vaginal insert reduces CS rate in nulliparous women of 24% compared
      to the other ways of administration (RR = 0.76, 95% CI = 0.59, 0.98). The risk of
      oxytocin use is reduced with the use of vaginal insert (RR = 0.64, 95% CI = 0.42,
      0.99). The risk of hyperstimulation is statistically higher in nulliparous women
      using vaginal insert than the other ways of administration with RR = 2.17, 95% CI
      = 1.08,4.33. CONCLUSIONS: In nulliparous women with unprepared cervix and intact
      membranes vaginal insert perform better than repeated vaginal doses since it is
      associated with more vaginal deliveries and less oxytocin use. Although vaginal
      insert is associated with more uterine hyperstimulation, it shows a protective
      effect toward caesarean section.

PMID- 22372422
TI  - Renal drug-drug interactions: what we have learned and where we are going.
AB  - INTRODUCTION: Transporters make a significant contribution to the pharmacokinetic
      and pharmacodynamic profiles of xenobiotics. The kidney, through the combination
      of passive glomerular filtration and active tubular secretion, plays an important
      role in the elimination of some drugs. A growing number of transporter-mediated
      drug-drug interactions (DDIs) have been described including a subset proposed to
      occur during the process of active tubular secretion in the renal proximal tubule
      (PT). AREAS COVERED: An overview of transporters expressed in the human PT is
      provided. Methodologies for studying transporters are discussed with an emphasis
      on recent advances in more pharmacologically relevant systems. The molecular
      mechanisms for known renal DDIs are explored, highlighting commonly implicated
      transporters. EXPERT OPINION: Clinically relevant renal DDIs are rare. While
      unlikely to affect most new drug candidates, it is difficult to prospectively
      predict when renal DDIs are likely to occur. Efforts to identify new transporters
      and establish predictive model systems have resulted in a rapid evolution in our
      understanding of renal DDIs. For example, the multidrug and toxin extrusion
      transporter 1 (MATE1) has emerged as a key transporter in the active tubular
      secretion of xenobiotics. We are headed toward a time when renal DDIs can be
      better predicted by preclinical studies.

PMID- 22372424
TI  - Imbibition of soybean seeds in warm water results in the release of copious
      amounts of Bowman-Birk protease inhibitor, a putative anticarcinogenic agent.
AB  - Protease inhibitors play a protective role against pathogenic microorganisms and
      herbivorous insects. The two predominant protease inhibitors of soybean seeds are
      the Kunitz trypsin inhibitor (KTI) and Bowman-Birk protease inhibitor (BBI). In
      this study, we report that soybean seeds incubated in warm water release large
      amounts of proteins into the surrounding media. Two-dimensional gel
      electrophoresis analysis of the seed exudates resulted in the separation of 93
      distinct protein spots out of which 90 spots were identified by LC-MS/MS. The
      basic 7S globulin and the BBI are the two predominant proteins found in the
      soybean seed exudates. In addition to 7S and 11S seed storage proteins, others
      known to protect the seeds against pathogens and pests including KTI, peroxidase,
      alpha-galactosidase, and endo-1.3-beta-glucanase were also identified in the seed
      exudates. Soybean seed exudate obtained by incubating the seeds in warm water was
      also able to inhibit the growth of human breast cancer cell line MCF-7. Since
      soybean seeds release large amounts of enzymatically active BBI when immersed in
      warm water, our procedure could be exploited as a simplified alternative method
      for the preparation of BBI concentrate which is being used as a cancer
      chemoprotective agent.

PMID- 22372425
TI  - 670 nm red light preconditioning supports Muller cell function: evidence from the
      white light-induced damage model in the rat retina.
AB  - Glial cells play an important role in the maintenance of normal structure and
      function of the neural components of the central nervous system. The Muller cells
      are one of the macroglial elements in the retina and their wide-ranging roles are
      responsible for the protection and proper functioning of the photoreceptors. In
      the present study, we aimed to test the effects of pretreatment with 670 nm red
      light on Muller cells in the light-induced model of retinal degeneration. Adult
      Sprague-Dawley albino rats were treated with 670 nm red light, from an LED source
      prior to exposure to bright (1000 lux) continuous light for 24 h. Muller cell
      specific markers were used to assess structural and functional changes in this
      cell type 1 week after contact with damaging light. Changes in gene (Edn2, LIF,
      TNF-alpha) and protein (S100beta, Vimentin, LIF, iNOS, GS, Cyclin-D1) levels and
      localization were evaluated using RT-qPCR, and immunohistochemistry. Our results
      showed that 670 nm light pretreatment ameliorates the light-induced alterations
      in the expression of Muller-cell specific markers for structure, stress,
      metabolism and inflammation. This suggests that 670 nm light preconditioning may
      promote neuroprotective effects in the retina from light-induced damage, possibly
      through pathways regulating the roles of Muller cells in maintaining retinal
      homeostasis.

PMID- 22372426
TI  - Suitability of infrared microspectroscopic imaging for histopathology of the
      uterine cervix.
AB  - AIMS:   Infrared microspectroscopy (IR-MSP) has been proposed for automated
      histological tissue differentiation of unstained specimens based on chemical
      analysis of cell and extracellular constituents. This study aimed to determine
      the accuracy of IR-MSP-based histopathology of cervical carcinoma sections with
      complex tissue architecture under practically relevant testing conditions.
      METHODS AND RESULTS:   In total, 46 regions of interest, covering an area of
      almost 50 mm(2) on sections derived from paraffin-embedded tissue of radical
      hysterectomy specimens, were analysed by IR-MSP (nominal resolution ~4.2 MUm).
      More than 2.8 million pixel spectra that were processed using fuzzy c-means
      clustering followed by hierarchical cluster analysis permitted image segmentation
      regarding different biochemical properties. Linear image registration was applied
      to compare these segmentation results with manual labelling on haematoxylin and
      eosin-stained references (resolution ~0.7 MUm). For recognition of nine tissue
      types, sensitivities were 42-91% and specificities were 79-100%, mostly being
      affected by peritumoral inflammatory responses. Algorithmic variation of the
      outline of dysplasia and carcinoma revealed a spatial preference of false values
      in tissue transition areas. CONCLUSIONS:   This imaging technique has potential
      as a new method for tissue characterization; however, the recognition accuracy
      does not justify a pathologist-independent tissue analysis, and the application
      is only possible in combination with concomitant conventional histopathology.

PMID- 22372427
TI  - A heat-activated calcium-permeable channel--Arabidopsis cyclic nucleotide-gated
      ion channel 6--is involved in heat shock responses.
AB  - An increased concentration of cytosolic calcium ions (Ca2+) is an early response
      by plant cells to heat shock. However, the molecular mechanism underlying the
      heat-induced initial Ca2+ response in plants is unclear. In this study, we
      identified and characterized a heat-activated Ca2+-permeable channel in the
      plasma membrane of Arabidopsis thaliana root protoplasts using reverse genetic
      analysis and the whole-cell patch-clamp technique. The results indicated that A.
      thaliana cyclic nucleotide-gated ion channel 6 (CNGC6) mediates heat-induced Ca2+
      influx and facilitates expression of heat shock protein (HSP) genes and the
      acquisition of thermotolerance. GUS and GFP reporter assays showed that CNGC6
      expression is ubiquitous in A. thaliana, and the protein is localized to the
      plasma membrane of cells. Furthermore, it was found that the level of cytosolic
      cAMP was increased by a mild heat shock, that CNGC6 was activated by cytosolic
      cAMP, and that exogenous cAMP promoted the expression of HSP genes. The results
      reveal the role of cAMP in transduction of heat shock signals in plants. The
      correlation of an increased level of cytosolic cAMP in a heat-shocked plant with
      activation of the Ca2+ channels and downstream expression of HSP genes sheds some
      light on how plants transduce a heat stimulus into a signal cascade that leads to
      a heat shock response.

PMID- 22372428
TI  - Validation study of KPICS SpermFinderTM by NicheVision Forensics, LLC for the
      identification of human spermatozoa.
AB  - Microscopic analysis for the identification of spermatozoa is commonly performed
      during the forensic examination of sexual assault evidence. Two widely utilized
      methods for the confirmation of the presence of spermatozoa are visualization of
      the cells via phase-contrast microscopy with wet mounted samples and bright field
      microscopy with histologically stained samples. The KPICS SpermFinderTM by
      NicheVision Forensics, LLC accelerates this time-consuming process via an
      automated microscope with an algorithm designed to locate spermatozoa on a
      Christmas tree histologically stained microscope slide. Upon a qualified
      scientist's review of the generated data, the KPICS SpermFinderTM was able to
      locate spermatozoa, typically finding on average 106.28% +/- 115.37% more
      spermatozoa than with manual examinations. The KPICS SpermFinderTM provided the
      location of identified cells with reproducible results.

PMID- 22372429
TI  - Possible high risk of thrombotic events in patients with paroxysmal nocturnal
      haemoglobinuria after discontinuation of eculizumab.

PMID- 22372430
TI  - Allogeneic hematopoietic stem cell transplantation following reduced-intensity
      conditioning regimen in children: a single-center experience.
AB  - This single-center retrospective study reported the outcome of 19 children
      treated with a reduced-intensity conditioning (RIC) regimen prior to allogeneic
      stem cell transplantation (allo-SCT), for hematologic malignancies (n = 17), bone
      marrow failure (n = 1), and neuroblastoma (n = 1). Children were ineligible for
      standard myeloablative conditioning because of severe comorbidities (n = 9), a
      previous auto or allo-SCT (n = 7) or a prior history of extensive chemotherapy (n
      = 3). All patients underwent a fludarabine-based RIC regimen, and received grafts
      from matched-related donors (n = 5), match-unrelated donors (n = 6), or unrelated
      cord blood (UCB, n = 8). In this series, two patients treated with UCB failed to
      engraft and 63% achieved full donor chimerism at day 100 after allo-SCT. With a
      median follow-up of 537 d (range, 115-4136), treatment-related mortality was 16%
      and overall survival was 47%. The principal cause of death was disease relapse (n
      = 7). Acute graft versus host disease (GVHD) occurred in 53% of patients, while
      only 10% developed extensive chronic GVHD. Overall, results from this series
      suggest that RIC allo-SCT can be a valid alternative treatment option in unfit
      children with malignant hematological diseases. Prospective studies are needed to
      enlarge pediatric experience in this domain and better identify those children
      more suitable for a RIC allo-SCT approach.

PMID- 22372431
TI  - Lateral graphene-hBCN heterostructures as a platform for fully two-dimensional
      transistors.
AB  - We propose that lateral heterostructures of single-atomic-layer graphene and
      hexagonal boron-carbon-nitrogen (hBCN) domains, can represent a powerful platform
      for the fabrication and the technological exploration of real two-dimensional
      field-effect transistors. Indeed, hBCN domains have an energy bandgap between 1
      and 5 eV, and are lattice-matched with graphene; therefore they can be used in
      the channel of a FET to effectively inhibit charge transport when the transistor
      needs to be switched off. We show through ab initio and atomistic simulations
      that a FET with a graphene-hBCN-graphene heterostructure in the channel can
      exceed the requirements of the International Technology Roadmap for
      Semiconductors for logic transistors at the 10 and 7 nm technology nodes.
      Considering the main figures of merit for digital electronics, a FET with gate
      length of 7 nm at a supply voltage of 0.6 V exhibits I(on)/I(off) ratio larger
      than 10(4), intrinsic delay time of about 0.1 ps, and a power-delay-product close
      to 0.1 nJ/m. More complex graphene-hBCN heterostructures can allow the
      realization of different multifunctional devices, translating on a truly two
      dimensional structure some of the device principles proposed during the first
      wave of nanoelectronics based on III-V heterostructures, as for example the
      resonant tunneling FET.

PMID- 22372432
TI  - Influence of low-temperature environmental exposure on the mechanical properties
      and structural stability of dental zirconia.
AB  - PURPOSE: The effect of dental fabrication procedures of zirconia monolithic
      restorations and changes in properties during low-temperature exposure in the
      oral environment is not completely understood. The purpose of this study was to
      investigate the effect of procedures for fabrication of dental restorations by
      low-temperature simulation and relative changes of flexural strength,
      nanoindentation hardness, Young's modulus, surface roughness, and structural
      stability of yttria-stabilized zirconia. MATERIALS AND METHODS: A total of 64
      zirconia specimens were prepared to simulate dental practice. The specimens were
      divided into the control group and the accelerated aging group. The simulated
      group followed the same procedure as the control group except for the aging
      treatment. Atomic force microscopy was used to measure surface roughness. The
      degree of tetragonal-to-monoclinic transformation was determined using X-ray
      diffraction. Nanoindentation hardness and modulus measurements were carried out
      on the surface of the zirconia specimens using a nanoindenter XP/G200 system. The
      yttria levels for nonaged and aged specimens were measured using energy
      dispersive spectroscopy. Flexural strength was determined using the piston-on
      three-ball test. The t-test was used to determine statistical significance.
      RESULTS: Means and standard deviations were calculated using all observations for
      each condition and evaluated using a group t-test (p < 0.05). The LTD treatment
      resulted in increased surface roughness (from 12.23 nm to 21.56 nm for Ra and
      15.06 nm to 27.45 nm for RMS) and monoclinic phase fractions (from 2% to 21%),
      with a concomitant decrease in hardness (from 16.56 GPa to 15.14 GPa) and modulus
      (from 275.68 GPa to 256.56 GPa). Yttria content (from 4.43% to 4.46%) and
      flexural strength (from 586 MPa to 578 MPa) were not significantly altered,
      supporting longer term in vivo function without biomechanical fracture.
      CONCLUSION: The LTD treatment induced the tetragonal-to-monoclinic transformation
      with surface roughening in zirconia prepared using dental procedures.

PMID- 22372433
TI  - New bacilli from shallow hydrothermal vents of Panarea Island (Italy) and their
      biotechnological potential.
AB  - AIMS: To characterize bacilli isolated from shallow hydrothermal vents of Panarea
      Island (Italy) and evaluate their biotechnological potential. METHODS AND
      RESULTS: Fifteen isolates were characterized by culture and molecular methods.
      Eleven isolates were thermophilic, six isolates were alkalophilic and four of
      them were haloalkalophilic. After 16S rRNA gene sequencing, four strains,
      exhibiting sequence similarity below 95% with deposited strains, may represent
      novel species of bacilli. One strain was strictly related to Geobacillus
      subterraneus, but shared phenotypic characteristics for which it could be
      considered a new strain of this species. Four strains were affiliated with
      different Bacillus spp. Most isolates produced gelatinase, lipases and amylase,
      and some were mercury tolerant. Exopolysaccharides (EPS) production was tested
      adding different sugars (glucose, sucrose, trehalose, fructose, ribose, xylose
      and mannose, 1% w/v) as a carbon source in a minimal medium. The highest EPS
      yield (185 mg l(-1)) was reached by strain 1A70 utilizing ribose as a carbon
      source. CONCLUSIONS: Novel strains of Geobacillus and indigenous ribotypes of
      Bacillus with biotechnological potential inhabit shallow vents of Panarea Island.
      SIGNIFICANCE AND IMPACT OF THE STUDY: New strains of thermophilic bacilli from
      Panarea are producers of useful biomolecules for industrial purposes as well as
      environmental and biotechnological applications.

PMID- 22372434
TI  - Isolation and survey of novel fluoroacetate-degrading bacteria belonging to the
      phylum Synergistetes.
AB  - Microbial dehalogenation of chlorinated compounds in anaerobic environments is
      well known, but the degradation of fluorinated compounds under similar conditions
      has rarely been described. Here, we report on the isolation of a bovine rumen
      bacterium that metabolizes fluoroacetate under anaerobic conditions, the mode of
      degradation and its presence in gut ecosystems. The bacterium was identified
      using 16S rRNA gene sequence analysis as belonging to the phylum Synergistetes
      and was designated strain MFA1. Growth was stimulated by amino acids with greater
      quantities of amino acids metabolized in the presence of fluoroacetate, but
      sugars were not fermented. Acetate, formate, propionate, isobutryate,
      isovalerate, ornithine and H(2)  were end products of amino acid metabolism.
      Acetate was the primary end product of fluoroacetate dehalogenation, and the
      amount produced correlated with the stoichiometric release of fluoride which was
      confirmed using fluorine nuclear magnetic resonance ((19) F NMR) spectroscopy.
      Hydrogen and formate produced in situ were consumed during dehalogenation. The
      growth characteristics of strain MFA1 indicated that the bacterium may gain
      energy via reductive dehalogenation. This is the first study to identify a
      bacterium that can anaerobically dehalogenate fluoroacetate. Nested 16S rRNA gene
      specific PCR assays detected the bacterium at low numbers in the gut of several
      herbivore species.

PMID- 22372435
TI  - Role of white blood cell and neutrophil counts in predicting spontaneous stone
      passage in patients with renal colic.
AB  - OBJECTIVE: To determine the clinical, imaging and laboratory variables that can
      predict spontaneous passage of ureteral stones causing renal colic and the role
      of white blood cell (WBC) and neutrophil counts for the prediction of spontaneous
      calculi passage. PATIENTS AND METHODS: A total of 156 patients who were referred
      to the emergency department complaining of renal colic due to a ureteral stone
      entered the analysis. Several clinical, laboratory and imaging parameters were
      evaluated for their potential ability to predict stone passage in a time interval
      of 1 month. The study design had two objectives. Primarily we analyzed all
      patients irrespective of stone size and secondly we analyzed patients with
      calculi of 10 mm maximum length. RESULTS: Spontaneous stone passage was observed
      in 96 (61.5%) patients in the overall population and in 84 (65.1%) of 129
      patients with calculi <10 mm. Increased concentrations of serum WBCs and
      neutrophils at the time of the acute phase of a renal colic were associated with
      increased likelihood of spontaneous passage. In the multivariate analyses we
      found that WBC and neutrophil counts were the most important predictors of stone
      elimination. CONCLUSIONS: Active surveillance of patients suffering from ureteral
      lithiasis is an acceptable option. Identifying the parameters which can predict
      those patients who will mostly benefit from this is of great importance. Based on
      our results, WBC and neutrophil counts should be considered when patients with
      renal colic secondary to ureteral calculi are evaluated since they can
      significantly add to spontaneous elimination prediction. Their consideration in
      addition to other important factors, like stone size and location, would maximize
      their predictive ability.

PMID- 22372436
TI  - Targeted laser reconstruction of skin scars using 10600-nm carbon dioxide
      fractional laser.

PMID- 22372437
TI  - Gastroenterology training in Australia: a perspective from the coal face.
AB  - BACKGROUND: The Royal Australasian College of Physicians is developing curricula
      for training. AIMS: We surveyed gastroenterology trainees on their training
      experience to establish whether training needs were being met. METHODS: An online
      anonymous survey of all gastroenterology trainees in 2009. RESULTS: Ninety-one
      per cent of trainees responded (105/115). Of these, 92% were adult, and 8% were
      paediatric trainees. Seventy four were core, and 31 were noncore trainees. Of
      those who had completed core training, the majority (86%) felt that their
      training had prepared them adequately for independent practice as a
      gastroenterologist. However, most respondents felt that core advanced training
      should be 3 years instead of 2 years. The majority (86%) saw a benefit in moving
      between hospitals during core training. Of the trainees managing inpatients, 57%
      were managing 10 or more per day, and 63% had three or more consultant ward
      rounds per week. The top three noncore fellowships were advanced endoscopy (44%),
      hepatology (28%) and inflammatory bowel disease (17%). Sixty-one per cent and 39%
      were undertaking a clinical and research fellowship respectively. Seventy-two per
      cent of core trainees attended up to three endoscopy lists per week, and 76% were
      on the on-call urgent endoscopy roster. For on-call endoscopy, 27% of third-year
      noncore trainees and 5% of core trainees were unsupervised. CONCLUSIONS: The
      majority of trainees felt that their core training would prepare them adequately
      for independent practice as gastroenterologists. Overall, trainees valued
      movement between hospitals during training and felt that core training should be
      3 years. Some trainees had inadequate consultant support for out-of-hours
      emergency endoscopy.

PMID- 22372438
TI  - Living between two worlds: two-phase culture systems for producing plant
      secondary metabolites.
AB  - The two-phase culture system is an important in vitro strategy to increase the
      production of secondary metabolites (SMs) by providing an enhanced release of
      these compounds from plant cells. Whereas the first phase supports cell growth,
      the second phase provides an additional site or acts as a metabolic sink for the
      accumulation of SMs and also reduces feedback inhibition. This review is focused
      on several aspects of the two-phase culture system and aims to show the diverse
      possibilities of employing this technique for the in vitro production of SMs from
      plant cells. Depending on the material used in the secondary phase, two-phase
      culture systems can be broadly categorised as liquid-liquid or liquid-solid. The
      choice of material for the second phase depends on the type of compound to be
      recovered and the compatibility with the other phase. Different factors affecting
      the efficiency of two-phase culture systems include the choice of material for
      the secondary phase, its concentration, volume, and time of addition. Factors
      such as cell elicitation, immobilization, and permeabilization, have been
      suggested as important strategies to make the two-phase culture system
      practically reliable on a commercial scale. Since there are many possibilities
      for designing a two-phase system, more detailed studies are needed to broaden the
      range of secondary phases compatible with the various plant species producing SMs
      with potential applications, mainly in the food and pharmacology industries.

PMID- 22372439
TI  - Hippocampal morphology and autobiographic memory in mild cognitive impairment and
      Alzheimer's disease.
AB  - Autobiographical memory (AM) comprises memories of one's own past that are
      characterized by a sense of subjective time and autonoetic awareness. AM deficits
      are among the major complaints of patients with Alzheimer's disease (AD) even in
      early or preclinical stages. However, little is known on the association between
      cerebral alterations and AM in mild cognitive impairment (MCI) and AD. In the
      current study, patients with AD or MCI and healthy controls underwent high
      resolution magnetic resonance imaging (MRI) and neuropsychological testing
      including semi-structured assessment of semantic and episodic AM of distinct
      lifetime periods. In MRI analysis, FSL-FIRST was used to automatically ascertain
      volume and shape of the hippocampal formation. Episodic, but not semantic AM loss
      was associated with morphological changes of the hippocampus, primarily involving
      the left hemisphere. According to shape analyses, these associations referred to
      regionally specific rather than global atrophy of the hippocampus. Our study
      demonstrates that loss of episodic AM early in the course of AD is associated
      with regionally confined hippocampal atrophy, thus supporting the multiple trace
      theory for the role of the hippocampus in episodic AM. Our findings are not only
      relevant for the understanding of memory function, but may also contribute to
      facilitating the early diagnosis of AD.

PMID- 22372440
TI  - The bHLH protein ROX acts in concert with RAX1 and LAS to modulate axillary
      meristem formation in Arabidopsis.
AB  - During post-embryonic shoot development, new meristems are initiated in the axils
      of leaves. They produce secondary axes of growth that determine morphological
      plasticity and reproductive efficiency in higher plants. In this study, we
      describe the role of the bHLH-protein-encoding Arabidopsis gene REGULATOR OF
      AXILLARY MERISTEM FORMATION (ROX), which is the ortholog of the branching
      regulators LAX PANICLE1 (LAX1) in rice and barren stalk1 (ba1) in maize. rox
      mutants display compromised axillary bud formation during vegetative shoot
      development, and combination of rox mutants with mutations in RAX1 and LAS, two
      key regulators of axillary meristem initiation, enhances their branching defects.
      In contrast to lax1 and ba1, flower development is unaffected in rox mutants.
      Over-expression of ROX leads to formation of accessory side shoots. ROX mRNA
      accumulates at the adaxial boundary of leaf and flower primordia. However, in the
      vegetative phase, axillary meristems initiate after ROX expression has
      terminated, suggesting an indirect role for ROX in meristem formation. During
      vegetative development, ROX expression is dependent on RAX1 and LAS activity, and
      all three genes act in concert to modulate axillary meristem formation.

PMID- 22372441
TI  - Results of laser therapy in twin-to-twin transfusion syndrome: our experience.
AB  - OBJECTIVE: The authors of this paper present the results of laser treatment in
      twin-to-twin transfusion syndrome. METHODS: Laser photocoagulation of
      communicating vessels was performed on 91 patients from April 2005 to June 2010,
      at the Medical University of Gdansk (Poland). Results of treatment were analyzed.
      RESULTS: The following results were achieved: at least one survival at delivery
      in 71 patients (83.5%), two survivors in 49 women (57.6%), and an overall
      survival rate of 70.6%. After the inclusion of neonatal deaths, at least one
      survival was reported in 65 women (76.5%) - 30 with two survivors (44.7%) and 27
      with one survivor (31.8%). The incidence of preterm rupture of membranes (4 cases
      - 4.3%), dual intrauterine fetal demise (7 cases - 7.4%) and miscarriage or
      delivery (8 cases - 8.5%) during the first week after surgery were the main
      reasons of pregnancy loss in the analyzed group. The frequency of cerebral palsy
      diagnosed after 6 months was 7%. CONCLUSIONS: Despite a lower incidence of dual
      neonatal survivals than in other series, the results of the first years of
      experience with laser treatment of twin-twin transfusion syndrome are
      encouraging, and prompt us to improve our surgical skills to achieve better
      outcomes.

PMID- 22372442
TI  - Production of a conjugated fatty acid by Bifidobacterium breve LMC520 from alpha
      linolenic acid: conjugated linolenic acid (CLnA).
AB  - This study was performed to characterize natural CLnA isomer production by
      Bifidobacterium breve LMC520 of human origin in comparison to conjugated linoleic
      acid (CLA) production. B. breve LMC520 was found to be highly active in terms of
      CLnA production, of which the major portion was identified as cis-9,trans-11,cis
      15 CLnA isomer by GC-MS and NMR analysis. B. breve LMC520 was incubated for 48 h
      using MRS medium (containing 0.05% L-cysteine . HCl) under different
      environmental conditions such as atmosphere, pH, and substrate concentration. The
      high conversion rate of alpha-linolenic acid (alpha-LNA) to CLnA (99%) was
      retained up to 2 mM alpha-LNA, and the production was proportionally increased
      nearly 7-fold with 8 mM by the 6 h of incubation under anaerobic conditions at a
      wide range of pH values (between 5 and 9). When alpha-LNA was compared with
      linoleic acid (LA) as a substrate for isomerization by B. breve LMC520, the
      conversion of alpha-LNA was higher than that of LA. These results demonstrated
      that specific CLnA isomer could be produced through active bacterial conversion
      at an optimized condition. Because many conjugated octadecatrienoic acids in
      nature are shown to play many positive roles, the noble isomer found in this
      study has potential as a functional source.

PMID- 22372443
TI  - CTNNB1 genotyping and APC screening in pediatric desmoid tumors: a proposed
      algorithm.
AB  - Desmoid fibromatosis is a rare, locally aggressive fibroblastic/myofibroblastic
      tumor that occasionally involves children. We examined a series of pediatric
      desmoids for CTNNB1 mutations, seen in sporadic tumors, and APC germline
      mutations, associated with familial adenomatous polyposis (FAP). Forty-four
      desmoids in pediatric patients were identified in the pathology files of 2 large
      referral centers (1995-2009). Clinical charts were reviewed for history of FAP.
      Germline APC gene mutations were determined on blood samples from patients
      presenting with FAP. Immunohistochemistry for beta-catenin was performed. CTNNB1
      genotyping was done by Sanger sequencing on formalin-fixed paraffin-embedded
      tissue. CTNNB1 mutations were observed in 29 of 44 (66%) desmoids, with 3
      mutations identified: T41A (64%), S45F (29%), and S45P (7%). Germline APC
      mutations were present in 7 (16%) desmoid patients. Eight (18%) patients had
      desmoids that were wild type for CTNNB1 and had no known clinical signs or family
      history suspicious for FAP at the time of testing or with extended follow up (n 
      =  6). Beta-catenin nuclear labeling was observed in 38 of 41 (92%) tested cases,
      34 (89%) of which showed mutations in either CTNNB1 (n  =  29) or APC (n  =  5).
      Nuclear localization of beta-catenin was seen in the majority of pediatric
      desmoids and was most often associated with somatic mutations in CTNNB1. However,
      a significant proportion of pediatric patients harbored germline mutations in
      APC. Given the implications, genetic counseling is recommended for children
      diagnosed with desmoid tumors lacking CTNNB1 mutations because this population is
      enriched for FAP patients.

PMID- 22372444
TI  - The nurse education imperative.

PMID- 22372445
TI  - The future of nursing depends on building coalitions.

PMID- 22372446
TI  - Social support and hopelessness in women undergoing infertility treatment in
      eastern Turkey.
AB  - OBJECTIVES: The aim of this study was to determine the social support and
      hopelessness in women undergoing infertility treatment in eastern Turkey. DESIGN
      AND SAMPLE: For this descriptive design study, the sample was composed of 456
      women. MEASURES: Beck's Hopelessness Scale (BHS) and the Multidimensional Scale
      of Perceived Social Support (MSPSS) were used. Percentile, correlation, unpaired
      t test, and one-way analysis of variance test were used for statistical analysis.
      RESULTS: The mean BHS score was 6.97 +/- 3.64, with a range of 0-19 while the
      mean MSPSS score was 61.98 +/- 16.05 with a range of 12-84. A negative
      correlation (r = -.336, p = .000) was noted between MSPSS scores and BHS scores.
      CONCLUSIONS: Hopelessness levels in women negatively correlate with reported
      level of social support. Informing health professionals about these issues will
      be an important step toward improving the quality and levels of social support
      given to women undergoing infertility treatment.

PMID- 22372447
TI  - Screening of neurodevelopmental delays in four communities of Mexico and Cuba.
AB  - OBJECTIVE: Nursing personnel applied a computerized evaluation instrument,
      Neuropediatric Development (NPED), and compared the prevalence of deviations from
      normal neurodevelopment in four communities of two Latin American countries,
      Mexico and Cuba. At the same time the feasibility of introducing this tool into
      Mexican local health centers was assessed. DESIGN AND SAMPLE: The NPED screening
      tool was applied to 400 children 1-60 months old from two suburban and one urban
      communities of Mexico and one urban community of Cuba. MEASURES: The NPED
      instrument was developed at the Neurosciences Centre of Cuba (Santos, & Perez
      Abalo, 2011; Santos, Perez-Abalo, & Alvarez, 2007), and explores three
      neurodevelopmental areas: language/communication, psychomotor, and sensory
      maturation (hearing/vision). RESULTS: Global (21.5%), language (16.5%),
      psychomotor (5.8%), and sensory (vision/audition; 2.3%/7%) failures were
      observed. Among Mexican communities, apart from the hearing test in which the
      urban community showed a significantly higher percentage of failures (p < .001),
      there were no other significant differences. When compared, the Cuban community
      showed a significantly higher proportion of audition failures in relation to the
      Mexican communities. CONCLUSIONS: The prevalence of deviations from normal
      neurodevelopment was highly similar between both countries, and the NPED system
      fulfils the necessary requisites for mass screening to be applied by nursing
      staff at a primary care level.

PMID- 22372448
TI  - The decision to receive influenza vaccination among nurses in North and South
      Dakota.
AB  - OBJECTIVES: We examined the relationships between factors (intention, habit,
      facilitating conditions, and social, cognitive, and affective factors) and
      nurses' decisions about influenza vaccinations to understand why some get
      vaccinated while others do not. DESIGN AND SAMPLE: In a descriptive correlational
      design, the Triandis model of interpersonal behavior was used to examine the
      decision of nurses to receive influenza vaccinations. Participants were a random
      sample (N=193) of registered nurses in North and South Dakota drawn from the
      respective state nursing licensing board lists. MEASURES: Instrument construction
      and mail survey procedures followed Dillman's tailored design method. RESULTS:
      The response rate exceeded 80%. The findings revealed significant, positive
      correlations among all model variables. Item analysis showed that false beliefs
      about influenza disease and vaccinations were prevalent and that there was a wide
      variation in employer support for nurses getting vaccinated. CONCLUSIONS:
      Educational and social marketing strategies may improve nurse's knowledge about
      influenza disease and vaccine and increase vaccine uptake. Employers should be
      encouraged to promote and improve influenza vaccine accessibility in the
      workplace. Additional study is needed to understand how best to strengthen the
      influence of intention and habit on the decision of nurses to receive influenza
      vaccinations.

PMID- 22372449
TI  - Listening to and learning from older adult Hurricane Katrina survivors.
AB  - OBJECTIVE: The objective of this pilot study was to explore how Hurricane Katrina
      affected older adult disaster survivors. DESIGN AND SAMPLE: Participants for this
      descriptive exploratory pilot study were recruited from churches and senior
      centers on the Gulf Coast of Mississippi. Of the 224 participants, one hundred
      provided additional comments at the end of a forced-response questionnaire.
      MEASURES: Manifest content analysis was used to examine the participants'
      comments by identifying, coding, and categorizing their responses to the open
      ended question. The codes were based on conditions and behaviors that might be
      exhibited by disaster victims. RESULTS: Themed categories were losses and needs,
      giving advice, justification for continuing to live in this disaster-prone
      region, deterrents and facilitators of home evacuation, spirituality and faith,
      manageability, bereavement, grief, anger, and natural debriefing. CONCLUSION: The
      strongest message of these survivors was the need to be heard by public health
      nurses, other public health officials preparing for disasters, and those in
      positions to render aid.

PMID- 22372450
TI  - Evaluation of a disaster-surge training for public health nurses.
AB  - OBJECTIVE: To examine the effect of a blended educational intervention (in-class
      and independent learning modules) developed to enhance Ohio PHN confidence in 25
      disaster surge competencies that address the PHN role and skills in Preparedness,
      Response, and Recovery. DESIGN AND SAMPLE: This was a quasi-experimental one
      group pre and post design. Participants (N = 54) completed pre- and
      postintervention surveys to evaluate intervention impact on self-perceived
      confidence and need for further training in the 25 competencies. MEASURES:
      Parallel pre and post surveys assessed participant evaluation of confidence and
      need for further competency training. Paired t tests and repeated measures ANOVA
      compared pre- and postsurvey results. RESULTS: Confidence in Preparedness,
      Response, and Recovery PHN disaster surge competencies significantly increased,
      whereas self-perceived need for further competency training correspondingly
      significantly decreased. CONCLUSIONS: A blended learning approach to disaster
      surge training effectively improved PHNs confidence in competency achievement and
      reduced perceived need for further training.

PMID- 22372451
TI  - Enhancing nursing students' understanding of poverty through simulation.
AB  - OBJECTIVES: The purposes of this study were (a) to describe the implementation of
      a poverty simulation, (b) to evaluate its use on nursing students' attitudes
      about poverty, and (c) to offer lessons learned. DESIGN AND SAMPLE: Using a mixed
      method design, a convenience sample of senior undergraduate nursing students (n =
      43) from a public university in a mid-Atlantic state participated in a poverty
      simulation experience. Students assumed the roles of real-life families and were
      given limited amounts of resources to survive in a simulated community. This
      simulation took place during a community health practicum clinical day. MEASURES:
      The short form of Attitudes about Poverty and Poor Populations Scale (APPPS) was
      adapted for this evaluation. This 21-item scale includes factors of personal
      deficiency, stigma, and structural perspective, which measures a range of diverse
      attitudes toward poverty and poor people. RESULTS: The results of this evaluation
      demonstrated that nursing students viewed the poverty simulation as an effective
      teaching strategy and actively participated. In particular, nursing students'
      scores on the factor of stigma of poverty demonstrated statistically significant
      changes. CONCLUSION: With proper planning, organization, and reflection, a
      poverty simulation experience can be a positive impetus for lifelong learning and
      civic engagement.

PMID- 22372452
TI  - Effectiveness of hand hygiene education in a basic nursing school curricula.
AB  - OBJECTIVES: Although hand hygiene (HH) is the cheapest and simplest tool for the
      prevention of hospital-acquired infections, poor HH compliance has been reported
      among health care professionals. A variety of factors influence the compliance
      with HH guidelines, the most important being the quality of the basic nursing
      education. The aims of this study were to analyze the effectiveness of the basic
      nursing education in relation to HH, and to explore the skills and attitudes
      toward HH among nursing students in praxis. DESIGN AND SAMPLE: A mixed-method
      approach using a cross-sectional survey combined with observation and curricular
      analysis was used. A total of 188 nursing students participated in the study.
      RESULTS: Content analysis revealed significant deficits in the quality of HH
      related information in basic nursing educational programs. Our results correlate
      directly with the reported insufficient levels of HH knowledge and the associated
      poor HH compliance by students during their training in clinical settings; as
      shown in observation and questionnaire-based surveys. CONCLUSIONS: The lack of
      compliance with HH standards among students lead to poor compliance among health
      care professionals in praxis. Consequently, the role of educational institutions
      in the prevention of hospital-acquired infections is significant, if the
      effectiveness of HH education is to be improved.

PMID- 22372453
TI  - Collaborative design and use of an agency feedback form for student clinical
      practicum experience in community/public health nursing.
AB  - Evaluation of students in community and public health (C/PH) nursing clinical
      practica is a challenge, especially when preceptors are expected to evaluate
      students from different academic nursing programs. The need for a standardized
      student evaluation tool was identified during federally funded collaborative
      meetings held between C/PH academic and practice partners in Northeastern
      Wisconsin. This article focuses on the development and appraisal of the
      standardized Agency Feedback Form (AFF) for Student Practicum Experience in
      Community/Public Health Nursing, which was designed to meet the identified need.
      Four baccalaureate nursing programs implemented the AFF for 3 purposes: (1) to
      provide a consistent and easy evaluation form for preceptors to complete; (2) to
      communicate useful information about students' individual professional behaviors
      observed during practicum; and (3) to increase students' and preceptors'
      understanding of the population-based nursing interventions, using the Public
      Health Intervention Wheel. Future uses and implications of the AFF are also
      discussed.

PMID- 22372454
TI  - An assessment of nurses' knowledge of botulism.
AB  - OBJECTIVE: To assess nurses' knowledge of botulism, a Centers for Disease Control
      Category A bioterrorism agent, one case of which constitutes an emergency.
      DESIGN: The study utilized survey research. SAMPLE: The cluster sample included
      1,414 registered nurses. MEASURE: The survey gathered demographic data and
      nurses' knowledge of the background, manifestation and management of botulism.
      RESULTS: The mean percentage of correct answers for the sample was 25.95%, with a
      standard deviation (SD) of +/-19.89%. Only 90 (6.3%) achieved 60% or more
      correct. Educational preparation, experience, specialty/area of practice and
      whether nurses had a class in disaster medicine were also examined and although
      differences were noted, none of these factors accounted for a score of 60% or
      above. CONCLUSIONS: The results of this study indicate the need for an assessment
      of the current education nurses receive about botulism.

PMID- 22372455
TI  - HIV prevention in the context of care: HIV testing and public health practice.
AB  - In this article, an argument is put forth that clinic-based HIV testing can
      function as an important aspect of public health HIV prevention. This assertion
      is not an outright declaration that all HIV testing is beneficial. Instead, it is
      the conclusion that the individual-focused initiative of HIV testing could, if
      structured properly, induce population-level HIV prevention benefits. This
      analysis was informed using the impact fraction model, the Anderson-May equation,
      current epidemiological information about HIV from Canada, the United States, and
      England, and the extant literature on the dynamics of HIV transmission. This
      conclusion could help inform the development of public and population health HIV
      testing and HIV prevention policies/practices.

PMID- 22372456
TI  - The nurse as a social worker.
AB  - In the early twentieth century the role of the public health nurse (PHN) was
      expanding to meet the needs of individuals, families, and communities. Among the
      ideas discussed in the early nursing literature was that of the social nurse.
      This role was conceptualized as a combined nurse and social worker. Much of the
      PHNs work was with people of the poorer classes who needed assistance with both
      the medical aspects of their disease, as well as help with social needs such as
      food, rent money, and bedding. In this reprint from The Visiting Nurse Quarterly
      (1911), Ellen La Motte, Nurse-in-Chief with the Tuberculosis Division of the
      Baltimore Health Department, argued for this combined role based on economic
      efficiency. As she pointed out, it was "economic waste" to have two sets of
      workers going into homes when the nurse was capable, with additional education,
      of carrying out both roles. Additionally, from La Motte's perspective the only
      way the nurse could move beyond her role as the "physician's handmaiden" was
      through "social training" that prepared her for a broader scope of practice than
      that received in the hospital-based nursing schools. In the end, however, she
      left it open to nurses as "reasonable beings" to determine the direction the
      profession would take on this issue. La Motte's words provide historical context
      for issues contemporary public health nursing leaders are addressing, such as
      inter-professional boundaries between nurses and public health workers,
      reductions in the public health workforce, and economic constraints faced by the
      healthcare system. The Institute of Medicine mandate for inter-professional
      practice within the healthcare system, however, presents opportunities for
      exploring new roles and practice models for nurses in conjunction with our
      partners in public health.

PMID- 22372457
TI  - The epidemiology, pathogenesis and histopathology of fatty liver disease.
AB  - Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and
      alcoholic liver disease (ALD), each of which is increasing in prevalence. Each
      represents a histological spectrum that extends from isolated steatosis to
      steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and
      insulin resistance, and is considered to be the liver manifestation of the
      metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines,
      adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard
      for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the
      literature, and described and compared the epidemiology, natural disease history,
      pathogenesis and histopathology of NAFLD and ALD.

PMID- 22372458
TI  - Fetal T cells and immunological tolerance.

PMID- 22372460
TI  - Hepatocellular carcinoma (HCC) in a patient with hepatitis B virus (HBV)
      infection.

PMID- 22372462
TI  - Spectroscopic and theoretical studies of Ga(III)protoporphyrin-IX and its
      reactions with myoglobin.
AB  - Ga(III)protoporphyrin-IX (Ga-PP) has been proposed as a model for the key
      interporphyrin interactions in malaria pigment. Unlike the paramagnetic parent
      iron heme derivatives, Ga-PP is readily soluble in methanol (MeOH). We report
      optical, mass spectroscopic, and theoretical results for Ga-PP as well as its
      reactions with myoglobin. UV-visible absorption and MCD spectroscopy show that Ga
      PP exhibits a typical spectrum for a main group metal: a Q-band at 539 nm and a B
      band at 406 nm when dissolved in MeOH. We also report optical data for
      Zn(II)protoporphyrin IX (Zn-PP) dissolved in MeOH, which exhibits a Q-band at 545
      nm and a B band at 415 nm. ESI mass spectral data for Ga-PP dissolved in MeOH
      show the presence of predominantly monomers, with smaller fractions of dimers
      [(Ga-PP)(2)] and trimers. UV-visible and MCD absorption spectroscopy and ESI mass
      spectral data demonstrate the successful insertion of monomeric Ga-PP into apo
      Mb. Ga-PP-Mb exhibits a B band at 417 nm and Q bands at 545 and 584 nm, which are
      all red-shifted from the free Ga-PP values. The calculated electronic structures
      and frontier molecular orbitals of Ga-PP, (Ga-PP)(2) and Zn-PP fit the previously
      reported trends in band energies and oscillator strengths as a function of
      molecular orbital energies. These new data can be applied to explain the
      experimentally observed optical spectroscopy. The observed Q-band energies are
      accounted for by calculated (HOMO-LUMO) gap of the frontier MOs, while the split
      in the two top occupied MOs accounts for the magnitude of the Q-band oscillator
      strength as well as the experimentally observed Q to B band energy separation.
      Although Ga-PP shares more spectroscopic properties with Zn-PP than it does with
      Fe(III)PPIX, the trivalent oxidation state allows this molecule to be used as a
      model for ferric hemes in heme proteins.

PMID- 22372463
TI  - BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia.
AB  - MECOM oncogene expression correlates with chronic myeloid leukaemia (CML)
      progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms
      reduces cell division at low cell density, inhibits colony-forming cells by 34%
      and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine
      kinase catalytic activity in K562 cells. We also show that both E and ME are
      expressed in CD34(+)  selected cells of both CML chronic phase (CML-CP), and non
      CML (normal) origin. Furthermore, MECOM mRNA and protein expression were
      repressed by imatinib mesylate treatment of CML-CP CD34(+)  cells, K562 and KY01
      cell lines whereas imatinib had no effect in non-CML BCR-ABL1 -ve CD34(+)  cells.
      Together these results suggest that BCR-ABL1 tyrosine kinase catalytic activity
      regulates MECOM gene expression in CML-CP progenitor cells and that the BCR-ABL1
      oncoprotein partially mediates its biological activity through MECOM. MECOM gene
      expression in CML-CP progenitor cells would provide an in vivo selective
      advantage, contributing to CML pathogenesis.

PMID- 22372464
TI  - Wind-drag estimation in a traffic accident involving a motor scooter and a
      tractor-trailer.
AB  - This case report describes a noncontact traffic accident involving a motor
      scooter and a tractor-trailer with a focus on the wind-drag effect. We used load
      cells to measure the drag force acting on a substantially similar motor scooter
      when a substantially similar tractor-trailer passes by it, taking into
      consideration various speeds of the tractor-trailer and distances between the two
      vehicles. A three-dimensional steady-state flow analysis was also performed by
      using the CFX program for computational fluid dynamics to examine the streamlines
      and the pressure distribution around the tractor-trailer at various speeds. From
      the experiment, for a separation distance of 1.0 m (3.28 ft) and a speed of 90
      km/h (55.9 mph), the maximum resultant drag force is 124.5 N (28 lb); this
      constitutes a degree of force that could abruptly disrupt the stability in
      maneuvering by an operator who is unaware of the approaching tractor-trailer. In
      addition, a single equation that relates the tractor-trailer speed to the drag
      force that acts on the motor scooter was derived on the basis of the Reynolds
      number (Re) and the wind-drag coefficient (C(d)): C(d) = 1.298 * 10(-7) Re.

PMID- 22372465
TI  - Large influence of cholesterol on solute partitioning into lipid membranes.
AB  - Cholesterol plays an important role in maintaining the correct fluidity and
      rigidity of the plasma membrane of all animal cells, and hence, it is present in
      concentrations ranging from 20 to 50 mol %. Whereas the effect of cholesterol on
      such mechanical properties has been studied exhaustively over the last decades,
      the structural basis for cholesterol effects on membrane permeability is still
      unclear. Here we apply systematic molecular dynamics simulations to study the
      partitioning of solutes between water and membranes. We derive potentials of mean
      force  for six different solutes permeating across 20 different lipid membranes
      containing one out of four types of phospholipids plus a cholesterol content
      varying from 0 to 50 mol %. Surprisingly, cholesterol decreases solute
      partitioning into the lipid tail region of the membranes much more strongly than
      expected from experiments on macroscopic membranes, suggesting that a laterally
      inhomogeneous cholesterol concentration and permeability may be required to
      explain experimental findings. The simulations indicate that the cost of breaking
      van der Waals interactions between the lipid tails of cholesterol-containing
      membranes account for the reduced partitioning rather than the surface area per
      phospholipid, which has been frequently suggested as a determinant for solute
      partitioning. The simulations further show that the partitioning is more
      sensitive to cholesterol (i) for larger solutes, (ii) in membranes with saturated
      as compared to membranes with unsaturated lipid tails, and (iii) in membranes
      with smaller lipid head groups.

PMID- 22372466
TI  - The UV-absorption spectrum of human iridal melanosomes: a new perspective on the
      relative absorption of eumelanin and pheomelanin and its consequences.
AB  - Photoemission electron microscopy is used to measure the absorption coefficients,
      epsilonc, of intact iridal stroma melanosomes isolated from dark brown and blue
      green human irides for the spectral range lambda=244-310 nm. These iridal stroma
      melanosomes were chosen because different colored irides produce organelles of
      varying eumelanin:pheomelanin ratios with similar size and morphology. Similar
      absorption spectra are found for the two types of melanosomes. The experimental
      spectra measured within are compared with both the extinction coefficient spectra
      obtained on soluble synthetic model systems and the monomeric precursors to each
      pigment.

PMID- 22372467
TI  - Determination of water in room temperature ionic liquids by cathodic stripping
      voltammetry at a gold electrode.
AB  - An electrochemical method based on cathodic stripping voltammetry at a gold
      electrode has been developed for the determination of water in ionic liquids. The
      technique has been applied to two aprotic ionic liquids, (1-butyl-3
      ethylimidazolium tetrafluoroborate and 1-butyl-3-methylimidazolium
      hexafluorophosphate), and two protic ionic liquids, (bis(2-hydroxyethyl)ammonium
      acetate and triethylammonium acetate). When water is present in an ionic liquid,
      electrooxidation of a gold electrode forms gold oxides. Thus, application of an
      anodic potential scan or holding the potential of the electrode at a very
      positive value leads to accumulation of an oxide film. On applying a cathodic
      potential scan, a sensitive stripping peak is produced as a result of the
      reduction of gold oxide back to gold. The magnitude of the peak current generated
      from the stripping process is a function of the water concentration in an ionic
      liquid. The method requires no addition of reagents and can be used for the
      sensitive and in situ determination of water present in small volumes of ionic
      liquids. Importantly, the method allows the determination of water in the
      carboxylic acid-based ionic liquids, such as acetate-based protic ionic liquids,
      where the widely used Karl Fischer titration method suffering from an
      esterification side reaction which generates water as a side product.

PMID- 22372468
TI  - Effect of the C-terminal domain of Vibrio proteolyticus chitinase A on the
      chitinolytic activity in association with pH changes.
AB  - AIMS: To reveal the cause of the difference in activity of chitinase A from
      Vibrio proteolyticus and chitinase A from a strain of Vibrio carchariae (a junior
      synonym of Vibrio harveyi), we investigated the pH-dependent activity of full
      length V. proteolyticus chitinase A and a truncated recombinant corresponding to
      the V. harveyi form of chitinase A. METHODS AND RESULTS: After overexpression in
      Escherichia coli strain DH5alpha, the full-length and truncated recombinant
      chitinases were purified by ammonium sulphate precipitation and anion exchange
      column chromatography. Chitinase activity was measured at various pH values using
      alpha-crystal and colloidal chitins as the substrate. The pH-dependent patterns
      of the relative specific activities for alpha-crystal chitin differed between the
      full-length and truncated recombinant chitinases, whereas those for colloidal
      chitin were similar to each other. CONCLUSION: The difference in the activity of
      V. proteolyticus chitinase A and V. harveyi chitinase A might be partly due to a
      change in the pH dependence of the chitinase activities against alpha-crystal
      chitin, resulting from C-terminal processing. SIGNIFICANCE AND IMPACT OF STUDY:
      The present results are important findings for not only ecological studies on the
      genus Vibrio in association with survival strategies, but also phylogenetic
      studies.

PMID- 22372469
TI  - Role of the surface-exposed leucine 155 in the metal ion binding loop of the CuA
      domain of cytochrome c oxidase from Thermus thermophilus on the function and
      stability of the protein.
AB  - The role of Leu155 in the metal ion binding loop in the soluble CuA binding
      domain of subunit II of cytochrome c oxidase from Thermus thermophilus (TtCuA)
      was investigated by site-specific mutations of this residue to arginine (L155R)
      and glutamic acid (L155E). The UV-visible absorption and electron paramagnetic
      resonance spectra suggested that the Cu(2)S(2) core of TtCuA was almost unchanged
      by the mutations. The redox potential of the metal center in the L155R mutant was
      ~20 mV higher than that in the WT protein, while that of the L155E mutant was
      almost the same as that of the wild type (WT-TtCuA). The rate of transfer of an
      electron from cytochrome c(552) to the L155E mutant was much lower than that of
      transfer to the WT protein, while that for transfer to the L155R mutant was
      similar to that of WT-TtCuA. The total reorganization energy was increased for
      both the mutant proteins compared to WT-TtCuA. The results suggest that the
      presence of a negatively charged residue at the site of Leu155 in TtCuA possibly
      disfavors the protein-protein interaction between the two redox partners. The
      mutation also affected the equilibrium pH dependence of the protein. The thermal
      and thermodynamic stability of TtCuA was drastically decreased upon the mutation,
      which is most prominent in the L155R mutant. These studies indicate that the
      hydrophobic patch at the surface of TtCuA consisting of Leu155 is important for
      the transfer of an electron between cytochrome c(552) and TtCuA.

PMID- 22372470
TI  - Smile esthetics: the influence of posterior maxillary gingival margin position.
AB  - PURPOSE: Successful replacement of posterior teeth using contemporary
      prosthodontic techniques in esthetically demanding cases relies upon visual
      replication of the natural posterior dentition and surrounding gingival
      architecture. There is currently little in the way of guidance for creating ideal
      or acceptable gingival relationships for posterior teeth. MATERIALS AND METHODS:
      A cross-sectional study was conducted comparing perceptions of four groups of
      individuals to six digitally manipulated images with various posterior teeth
      gingival margin position configurations. A total of 120 volunteers aged 12 years
      to 80 years, comprising 30 patients diagnosed with hypodontia, 30 patients
      diagnosed with periodontal disease, 30 patients without either condition, and 30
      qualified dentists were recruited from the Eastman Dental Institute & Hospital,
      London. A ranked order of preference for each set was obtained, and this was
      repeated after a minimum time interval of 10 minutes. RESULTS: Posterior gingival
      margin configurations from 0 mm to 2 mm (measured at the first premolar) were
      deemed most esthetic by the majority of the patient groups; dentists had a strong
      preference for the 1 mm configuration. Dentists appeared to be more perceptive to
      the alterations in gingival positions. CONCLUSIONS: Posterior gingival margin
      configurations where the first premolar margins were 1 mm lower than the canine
      margins were deemed the most esthetically pleasing; however, it is likely that a
      range of acceptability of 1 mm deviations from this ideal exists.

PMID- 22372471
TI  - The science of cellulite treatment and its long-term effectiveness.
AB  - Cellulite is a disorder in which adipose tissue extends through the dermis,
      producing a cosmetically displeasing dimpling in the affected areas. While many
      treatments claim to be able to improve the appearance of cellulite, the long-term
      effectiveness of these treatments and whether the logic behind these treatments
      can lead to a long-term improvement has not been extensively reviewed. In the
      following review, our goal is to assess the various cellulite treatments and
      evaluate the length of time results persist and whether the science behind the
      treatments warrants them as reliable and effective treatments for cellulite.

PMID- 22372472
TI  - Gliotoxin contamination in and pre- and postfermented corn, sorghum and wet
      brewer's grains silage in Sao Paulo and Rio de Janeiro State, Brazil.
AB  - AIMS: The aim of this study was to determine total fungal counts and the relative
      density of Aspergillus fumigatus and related species in silage samples intended
      for bovines before and after fermentation as well as to monitor the natural
      occurrence of gliotoxin in silage samples (pre- and postfermentation). METHODS
      AND METHODS: The survey was performed in farms located in Sao Paulo and Rio de
      Janeiro States in Brazil. In addition, the ability of A. fumigatus strains and
      related species strains to produce gliotoxin was also evaluated. A total of 300
      samples were taken, immediately after opening of the silo (3-5 months) and during
      the ensiling period. Fungal counts were done by the surface-spread method.
      Gliotoxin production ability of isolates and natural contamination were
      determined by HPLC. RESULTS: All postfermented samples had a total number of
      moulds exceeding 1 * 10(4) CFU g(-1), with Aspergillus sp. as the most prevalent
      genus. Frequency of strains, among A. fumigatus and related species, was able to
      produce gliotoxin was similar in pre- and postfermented samples, except for
      sorghum, which showed differences between both kinds of samples. The highest
      toxin levels were produced by strains isolated from postfermented samples. More
      than 50% of the samples showed gliotoxin contamination levels that exceeded
      concentrations known to induce immunosuppressive and apoptotic effects in cells.
      CONCLUSIONS: The present data suggest that care should be taken because gliotoxin
      contamination in feedstuffs could affect productivity and also present a health
      risk for herds. SIGNIFICANCE AND IMPACT OF THE STUDY: Gliotoxin was found at
      quite important concentrations levels in pre- and postfermented substrates and
      its presence could therefore probably affect the productivity and health of
      herds. Current conservation and management practices do not avoid contamination
      with A. fumigatus on silage. Therefore, farm workers should be adequately
      protected during its handling.

PMID- 22372473
TI  - Predictors of the 2-year recurrence and persistence of alcohol dependence.
AB  - AIMS: To identify independent risk factors of the recurrence of alcohol
      dependence (AD) in people with a remitted disorder at baseline and persistence of
      AD in people with a current disorder at baseline. DESIGN: Prospective cohort
      study with assessments at baseline and 2-year follow-up. SETTING: Recruitment
      from the general population, primary care and out-patient mental health-care
      services. PARTICIPANTS: People with remitted AD (n = 253) and current AD (n =
      135). MEASUREMENTS: Recurrence and persistence of AD during 2-year follow-up were
      established using the Composite International Diagnostic Interview (CIDI)
      interview based on DSM-IV. Logistic regression analyses were performed to explore
      the role of potential risk factors (i.e. baseline severity of alcohol problems,
      measures for depression and anxiety, socio-demographics, vulnerability factors
      and addiction-related factors) as independent predictors of a negative course.
      FINDINGS: Overall recurrence and persistence rates of AD were 14.6 and 40.7%,
      respectively, and were highly conditional on the severity of alcohol problems
      [adjusted odds ratio (OR) per standard deviation (SD) increase: OR = 3.64, 95%
      confidence interval (CI): 2.21-6.01 and OR = 2.12, 95% CI: 1.32-3.40,
      respectively). Severity of depressive/anxiety symptoms was an additional
      independent predictor of the recurrence of AD, whereas male gender and high
      education were significant independent risk factors of the persistence of AD.
      CONCLUSIONS: Alcohol dependence has a dynamic course, with only moderate levels
      of diagnostic stability. Both recurrence and persistence of alcohol dependence
      are highly dependent on severity of baseline alcohol problems, whereas severity
      of depressive/anxiety symptoms predicts only the recurrence of alcohol
      dependence. Both measures may be useful in identifying people at an increased
      risk of a negative course and who could be targeted by prevention strategies.

PMID- 22372474
TI  - Wet chemical functionalization of III-V semiconductor surfaces: alkylation of
      gallium arsenide and gallium nitride by a Grignard reaction sequence.
AB  - Crystalline gallium arsenide (GaAs) (111)A and gallium nitride (GaN) (0001)
      surfaces have been functionalized with alkyl groups via a sequential wet chemical
      chlorine activation, Grignard reaction process. For GaAs(111)A, etching in HCl in
      diethyl ether effected both oxide removal and surface-bound Cl. X-ray
      photoelectron (XP) spectra demonstrated selective surface chlorination after
      exposure to 2 M HCl in diethyl ether for freshly etched GaAs(111)A but not
      GaAs(111)B surfaces. GaN(0001) surfaces exposed to PCl(5) in chlorobenzene showed
      reproducible XP spectroscopic evidence for Cl-termination. The Cl-activated
      GaAs(111)A and GaN(0001) surfaces were both reactive toward alkyl Grignard
      reagents, with pronounced decreases in detectable Cl signal as measured by XP
      spectroscopy. Sessile contact angle measurements between water and GaAs(111)A
      interfaces after various levels of treatment showed that GaAs(111)A surfaces
      became significantly more hydrophobic following reaction with C(n)H(2n-1)MgCl (n
      = 1, 2, 4, 8, 14, 18). High-resolution As 3d XP spectra taken at various times
      during prolonged direct exposure to ambient lab air indicated that the resistance
      of GaAs(111)A to surface oxidation was greatly enhanced after reaction with
      Grignard reagents. GaAs(111)A surfaces terminated with C(18)H(37) groups were
      also used in Schottky heterojunctions with Hg. These heterojunctions exhibited
      better stability over repeated cycling than heterojunctions based on GaAs(111)A
      modified with C(18)H(37)S groups. Raman spectra were separately collected that
      suggested electronic passivation by surficial Ga-C bonds at GaAs(111)A.
      Specifically, GaAs(111)A surfaces reacted with alkyl Grignard reagents exhibited
      Raman signatures comparable to those of samples treated with 10% Na(2)S in tert
      butanol. For GaN(0001), high-resolution C 1s spectra exhibited the characteristic
      low binding energy shoulder demonstrative of surface Ga-C bonds following
      reaction with CH(3)MgCl. In addition, 4-fluorophenyl groups were attached and
      detected after reaction with C(6)H(4)FMgBr, further confirming the susceptibility
      of Cl-terminated GaN(0001) to surface alkylation. However, the measured
      hydrophobicities of alkyl-terminated GaAs(111)A and GaN(0001) were markedly
      distinct, indicating differences in the resultant surface layers. The results
      presented here, in conjunction with previous studies on GaP, show that atop Ga
      atoms at these crystallographically related surfaces can be deliberately
      functionalized and protected through Ga-C surface bonds that do not involve
      thiol/sulfide chemistry or gas-phase pretreatments.

PMID- 22372475
TI  - Psychometric properties of a structured interview guide for the rating for
      anxiety in dementia.
AB  - OBJECTIVES: The Rating Anxiety in Dementia (RAID; Shankar, K.K., Walker, M.,
      Frost, D., & Orrell, M.W. (1999). The development of a valid and reliable scale
      for rating anxiety in dementia (RAID). Aging and Mental Health, 3, 39-49.) is a
      clinical rating scale developed to evaluate anxiety in persons with dementia.
      This report explores the psychometric properties and clinical utility of a new
      structured interview format of the RAID (RAID-SI), developed to standardize
      administration and scoring based on information obtained from the patient, an
      identified collateral, and rater observation. METHOD: The RAID-SI was
      administered by trained master's level raters. Participants were 32 persons with
      dementia who qualified for an anxiety treatment outcome study. Self-report
      anxiety, depression, and quality of life measures were administered to both the
      person with dementia and a collateral. RESULTS: The RAID-SI exhibited adequate
      internal consistency reliability and inter-rater reliability. There was also some
      evidence of construct validity as indicated by significant correlations with
      other measures of patient-reported and collateral-reported anxiety, and non
      significant correlations with collateral reports of patient depression and
      quality of life. Further, RAID-SI scores were significantly higher in persons
      with an anxiety diagnosis compared to those without an anxiety diagnosis.
      CONCLUSION: There is evidence that the RAID-SI exhibits good reliability and
      validity in older adults with dementia. The advantage of the structured interview
      format is increased standardization in administration and scoring, which may be
      particularly important when RAID raters are not experienced clinicians.

PMID- 22372476
TI  - Nanopore detection of single molecule RNAP-DNA transcription complex.
AB  - In the past decade, a number of single-molecule methods have been developed with
      the aim of investigating single protein and nucleic acid interactions. For the
      first time we use solid-state nanopore sensing to detect a single E. coli RNAP
      DNA transcription complex and single E. coli RNAP enzyme. On the basis of their
      specific conductance translocation signature, we can discriminate and identify
      between those two types of molecular translocations and translocations of bare
      DNA. This opens up a new perspectives for investigating transcription processes
      at the single-molecule level.

PMID- 22372477
TI  - Reassessing the clinical significance of chorionic membrane microcysts and linear
      necrosis.
AB  - Recent studies have suggested that 2 lesions of the fetal membranes, linear
      necrosis at the choriodecidual junction and chorionic membrane microcysts, are
      markers of uteroplacental ischemia. To evaluate this hypothesis, we examined 807
      placentas from unselected, consecutive deliveries at a single hospital over
      approximately 6 months with specific recording of the presence of chorionic
      microcysts or linear membrane necrosis. Clinical factors that might indicate
      uteroplacental ischemia were abstracted from the pathology report, including
      small for gestational age, pregnancy-induced hypertension, meconium macrophages
      in the membranes, infarctions, and small placenta. We found that both chorionic
      microcysts and linear membrane necrosis are very common lesions in unselected
      placentas, involving 28% and 18% of all placentas, respectively. There was no
      correlation between the presence of chorionic membrane microcysts and any marker
      of uteroplacental ischemia. Linear necrosis correlated only with the presence of
      meconium macrophages. We conclude that these membrane changes are not a useful
      marker of ischemia in an unselected population of placentas. We suggest caution
      in the interpretation of these findings, to avoid overdiagnosing ischemia or
      other pathologic processes.

PMID- 22372478
TI  - Adsorption and dilatational rheology of heat-treated soy protein at the oil-water
      interface: relationship to structural properties.
AB  - We evaluated the influence of heat treatment on interfacial properties
      (adsorption at the oil-water interface and dilatational rheology of interfacial
      layers) of soy protein isolate. The related structural properties of protein
      affecting these interfacial behaviors, including protein unfolding and
      aggregation, surface hydrophobicity, and the state of sulfhydryl group, were also
      investigated. The structural and interfacial properties of soy protein depended
      strongly on heating temperature (90 and 120  degrees C). Heat treatment at 90 
      degrees C induced an increase in surface hydrophobicity due to partial unfolding
      of protein, accompanied by the formation of aggregates linked by disulfide bond,
      and lower surface pressure at long-term adsorption and similar dynamic
      interfacial rheology were observed as compared to native protein. Contrastingly,
      heat treatment at 120  degrees C led to a higher surface activity of the protein
      and rapid development of intermolecular interactions in the adsorbed layer, as
      evidenced by a faster increase of surface pressure and dilatational modulus. The
      interfacial behaviors of this heated protein may be mainly associated with more
      flexible conformation and high free sulfhydryl group, even if some exposed
      hydrophobic groups are involved in the formation of aggregates. These results
      would be useful to better understand the structure dependence of protein
      interfacial behaviors and to expand utilization of heat-treated protein in the
      formulation and production of emulsions.

PMID- 22372479
TI  - The importance of credentialing: the time for certification is here.

PMID- 22372480
TI  - What is a gap and how do I fill it?
AB  - Planning educational activities for continuing nursing education(CNE) is focused
      on developing learning experiences that "fill the gap" between where the learner
      is and where he or she needs to be. This column explores needs assessment and gap
      analysis processes that guide planning, implementation, and evaluation of CNE
      activities.

PMID- 22372481
TI  - Transforming engagement in learning through innovative technologies: using an
      audience response system in nursing orientation.
AB  - This column discusses using an audience response system in nursing orientation to
      enhance participant engagement while increasing educator efficiency.

PMID- 22372482
TI  - Working to implement the recommendations of the future of nursing report.
AB  - When national efforts and recommendations are developed, it is often difficult
      and complex to actualize a plan for their implementation. This column attempts to
      provide examples of the work being done by nurses and their partners across the
      country in actualizing the recommendations of The Future of Nursing report.

PMID- 22372484
TI  - Hepatocellular adenoma in glycogen storage disorder type I: a clinicopathological
      and molecular study.
AB  - AIMS:   Glycogen storage disease type I is a metabolic disorder resulting from
      deficiency of the glucose-6-phosphate complex. Long-term complications include
      the development of hepatocellular adenoma (HCA). In this retrospective study, our
      aim was to reclassify according to geno-phenotypic characteristics nodular
      lesions identified in hepatectomy specimens of such patients transplanted between
      1998 and 2008 at our institution. METHODS AND RESULTS:   Clinicopathological data
      of seven consecutive transplanted patients with glycogen storage disease type I
      were reviewed. Liver nodules were re-examined histologically and by
      immunohistochemistry. Molecular analysis was performed additionally in a case
      with specific features. Four patients had multiple tumours. We concluded that 26
      of 38 nodules available for study had features of inflammatory hepatocellular
      adenomas, seven comprised adenomas not otherwise specified and five were found to
      be focal nodular hyperplasia. CONCLUSIONS:   Further studies are needed to
      clarify the pathogenesis of hepatocellular adenomas in glycogen storage disease;
      in particular to determine whether they share abnormal metabolic pathways with
      inflammatory adenomas in the general population. Testing for acute phase proteins
      may be a helpful tool in the early detection of HCA in such patients. Finally,
      there is a need to further define their risk of malignant transformation, in
      relation to age and possible cofactors.

PMID- 22372485
TI  - Periconceptional folic acid and teratogenic drug use in women undergoing
      fertility treatments.
AB  - OBJECTIVE: To evaluate periconception drug use in women undergoing fertility
      treatment and compare it to women with spontaneous pregnancies. METHODS:
      Retrospective observational cohort study on reproductive-age women. Data on
      pregnancies, fertility treatments, prescription fillings and demographics were
      extracted from Clalit Health Services computerized systems. Two quality measures
      were evaluated: periconception folic acid prescription fillings and use of
      potentially hazardous drugs in early pregnancy. RESULTS: There were 12,891
      fertility treatment cycles in 4868 women; and 4968 women had spontaneous
      pregnancy. Periconceptional folic acid use was low and similar in both groups
      (31.3% of fertility cycles versus 29.9% of spontaneous pregnancies, p = 0.07). In
      the infertility group, 293 prescriptions for potentially hazardous drugs were
      filled within 45 days after the beginning of a fertility cycle (2.3% of cycles)
      compared to only 47 (0.9%) in women with spontaneous pregnancy (p < 0.001).
      CONCLUSIONS: The periconception medical care of women who undergo fertility
      treatment is suboptimal and is not better than in women with spontaneous
      pregnancies. Folic acid use that can reduce the risk of congenital anomalies is
      underused; whereas the use of potentially hazardous drugs in early pregnancy is
      significant. More intensive and targeted counseling regarding drug use before
      pregnancy is urgently needed.

PMID- 22372486
TI  - The role of oxytocin and oxytocin receptor gene variants in childhood-onset
      aggression.
AB  - Aggressive antisocial behaviours are the most common reasons why adolescents are
      referred to mental health clinics. Antisocial behaviours are costly in social and
      financial terms. The aetiology of aggressive behaviours is unknown but growing
      evidence suggests it is heritable, and certain genetic variants have been
      implicated as contributing factors. The purpose of this study was to determine
      whether genes regulating the hormone oxytocin (OXT) were associated with
      aggressive antisocial behaviour. The case-control study sample consisted of 160
      cases of children displaying extreme, persistent and pervasive aggressive
      behaviour. This case sample was compared with 160 adult controls. We used
      polymerase chain reaction (PCR) to determine the genotype for three oxytocin gene
      (OXT) single nucleotide polymorphisms (SNPs): rs3761248, rs4813625 and rs877172;
      and five oxytocin receptor gene (OXTR) SNPs: rs6770632, rs11476, rs1042778,
      rs237902 and rs53576. Genotypic analyses were performed using stata, while
      differences in haplotypic and allelic frequencies were analysed using Unphased.
      We also performed within-case analyses (n = 236 aggressive cases) examining
      genotypic and allelic associations with callous-unemotional (CU) scores (as
      measured by the psychopathic screening device). OXTR SNPs rs6770632 and rs1042778
      may be associated with extreme, persistent and pervasive aggressive behaviours in
      females and males, respectively. These and haplotype results suggest gender
      specific effects of SNPs. No significant differences were detected with respect
      to CU behaviours. These results may help to elucidate the biochemical pathways
      associated with aggressive behaviours, which may aid in the development of novel
      medications.

PMID- 22372487
TI  - Formation of cationic [RP5Cl](+)-cages via insertion of [RPCl](+)-cations into a
      P-P bond of the P4 tetrahedron.
AB  - Fluorobenzene solutions of RPCl(2) and a Lewis acid such as ECl(3) (E = Al, Ga)
      in a 1:1 ratio are used as reactive sources of chlorophosphenium cations
      [RPCl](+), which insert into P-P bonds of dissolved P(4). This general protocol
      represents a powerful strategy for the synthesis of new cationic chloro
      substituted organophosphorus [RP(5)Cl](+)-cages as illustrated by the isolation
      of several monocations (21a-g(+)) in good to excellent yields. For singular
      reaction two possible reaction mechanisms are proposed on the basis of quantum
      chemical calculations. The intriguing NMR spectra and structures of the obtained
      cationic [RP(5)Cl](+)-cages are discussed. Furthermore, the reactions of
      dichlorophosphanes and the Lewis acid GaCl(3) in various stoichiometries are
      investigated to obtain a deeper understanding of the species involved in these
      reactions. The formation of intermediates such as RPCl(2).GaCl(3) (14) adducts,
      dichlorophosphanylchlorophosphonium cations [RPCl(2)-RPCl](+) (16(+)) and
      [RPCl(2)-RPCl-GaCl(3)](+) (17(+)) in reaction mixtures of RPCl(2) and GaCl(3) in
      fluorobenzene strongly depends on the basicity of the dichlorophosphane RPCl(2)
      (R = tBu, Cy, iPr, Et, Me, Ph, C(6)F(5)) and the reaction stoichiometry.

PMID- 22372488
TI  - The impact of photoperiod insensitive Ppd-1a mutations on the photoperiod pathway
      across the three genomes of hexaploid wheat (Triticum aestivum).
AB  - Flowering time is a trait that has been extensively altered during wheat
      domestication, enabling it to be highly productive in diverse environments and
      providing a rich source of variation for studying adaptation mechanisms.
      Hexaploid wheat is ancestrally a long-day plant, but many environments require
      varieties with photoperiod insensitivity (PI) that can flower in short days. PI
      results from mutations in the Ppd-1 gene on the A, B or D genomes, with
      individual mutations conferring different degrees of earliness. The basis of this
      is poorly understood. Using a common genetic background, the effects of A, B and
      D genome PI mutations on genes of the circadian clock and photoperiod pathway
      were studied using genome-specific expression assays. Ppd-1 PI mutations did not
      affect the clock or immediate clock outputs, but affected TaCO1 and TaFT1, with a
      reduction in TaCO1 expression as TaFT1 expression increased. Therefore, although
      Ppd-1 is related to PRR genes of the Arabidopsis circadian clock, Ppd-1 affects
      flowering by an alternative route, most likely by upregulating TaFT1 with a
      feedback effect that reduces TaCO1 expression. Individual genes in the circadian
      clock and photoperiod pathway were predominantly expressed from one genome, and
      there was no genome specificity in Ppd-1 action. Lines combining PI mutations on
      two or three genomes had enhanced earliness with higher levels, but not earlier
      induction, of TaFT1, showing that there is a direct quantitative relationship
      between Ppd-1 mutations, TaFT1 expression and flowering.

PMID- 22372489
TI  - Optimal restoration of dental esthetics and function with advanced implant
      supported prostheses: a clinical report.
AB  - For more than 25 years, computer-aided design and computer-aided manufacturing
      (CAD/CAM) technology has been used in implant restorative dentistry. Today this
      technology offers a means of milling titanium frameworks that fit dental implants
      accurately. This report presents a restoratively driven protocol employing
      advanced implant restorative and surgical techniques. Treatment of a patient with
      advanced periodontitis with extensive loss of hard and soft tissues is presented.
      After extraction of the patient's remaining hopeless teeth, dental implants were
      placed, along with interim, fixed-margin abutments and abutment protection caps.
      Two days later, acrylic resin fixed-interim prostheses restored the patient's
      esthetics and partial masticatory function. After implant osseointegration,
      maxillary, and mandibular frameworks for definitive prostheses were milled from
      Ti alloy, using one specific CAD/CAM technology. The benefits of this technology
      are also discussed.

PMID- 22372490
TI  - Gastroenterology training in Australia: how much is enough?
AB  - BACKGROUND: Advanced training in gastroenterology currently consists of 2 years
      of core training and 1 elective (non-core) year. We surveyed gastroenterologists
      2-7 years following completion of training to determine the strengths and
      weaknesses of their training. METHODS: All gastroenterologists were invited to
      participate in an anonymous online survey. RESULTS: There was a 46% response rate
      (49/110). Eighty-one per cent were male with most aged 36-45. Respondents felt
      that the current training programme prepared them well for public practice and
      endoscopy but less well for private practice, ambulatory care, surgical aspects
      of gastroenterology and functional gastrointestinal disorders. Most had faced
      challenges transitioning to consultant practice. The majority (53%) spent more
      than the standard 3 years to complete training in gastroenterology. The top three
      subspecialty Fellowships were in endoscopy (45%), inflammatory bowel disease
      (29%) and hepatology (23%). In their elective year, 42% undertook a predominantly
      clinical year (registrar-type position in general or subspecialty
      gastroenterology), 28% engaged in research while 24% trained in another
      specialty. Seventy-eight per cent were in full-time work, and 36% were
      supervising trainees. Ninety-eight per cent felt that it was beneficial for
      trainees to move between hospitals during the core years of their advanced
      training. CONCLUSIONS: The current Australian gastroenterology training programme
      is generally adequate in preparing trainees for consultant practice but could be
      improved by increased emphasis on areas such as private practice, ambulatory
      gastroenterology and functional gastrointestinal diseases. Exposure to a variety
      of experiences by training in several different hospitals during core training
      was universally viewed as being important.

PMID- 22372492
TI  - The forensic deaths caused by pesticide poisoning between the years 2006 and 2009
      in Izmir, Turkey.
AB  - Pesticide poisoning is still a significant health problem in Turkey. We conducted
      a retrospective study of autopsy cases at Izmir Branch of the Council of Forensic
      Medicine to describe the characteristics of deaths caused by pesticide poisoning
      between 2006 and 2009. The distributions of the cases according to gender and age
      were as follows: men 74.1% (n = 40, mean [+/-SD] age, 44.7 +/- 14.1), women 25.9%
      (n = 14, mean [+/-SD] age, 39.2 +/- 18.9). The majority of pesticide-poisoning
      deaths were suicides (n = 43, 80%) followed by accidents (n = 4, 8%) and homicide
      (n = 1, 2%). The manner of death could not be determined in six cases (11%).
      Suicides mostly occurred at home (n = 26, 63%) (p < 0.05). Methomyl was the most
      frequent pesticide (n = 9, 17%) among the all cases. This study reported that
      most of the pesticides found in poisoning cases were highly hazardous types.
      Combined efforts of medical professionals and law makers are needed for enacting
      strict laws against highly hazardous pesticides.

PMID- 22372491
TI  - Prodigiosin down-regulates SKP2 to induce p27(KIP1)  stabilization and
      antiproliferation in human lung adenocarcinoma cells.
AB  - BACKGROUND AND PURPOSE: High levels of SKP2 are a poor prognostic factor in
      multiple human cancers and mostly correlate with low p27(KIP1) levels.
      Prodigiosin is a bacterial tripyrrole pigment with strong pro-apoptotic activity.
      Induction of cell cycle blockade underlies one of its anticancer actions but the
      mechanisms involved are unclear. The aim of this study was to explore the role of
      the SKP2-p27(KIP1) axis in prodigiosin's cytostatic effect on human lung
      adenocarcinoma cells. EXPERIMENTAL APPROACH: Prodigiosin's effects on cell cycle
      progression and long-term cell proliferation of human lung adenocarcinoma cells
      were characterized by flow cytometry and colony formation assay, respectively.
      Real-time RT-PCR and promoter activity analyses were performed for assessing
      transcriptional control, while cycloheximide chase analysis evaluated protein
      stability. Immunoblotting was employed for mechanistic study. KEY RESULTS:
      Prodigiosin increased p27(KIP1) expression mainly by stabilizing p27(KIP1)
      through transcriptional repression of SKP2. Importantly, SKP2 overexpression or
      p27(KIP1) depletion restored the colony forming capacity of prodigiosin-treated
      cells. Furthermore, prodigiosin induced PKB dephosphorylation, leading to PKB
      inhibition as revealed by decreased serine 9 phosphorylation of GSK-3beta.
      Constitutive PKB activation reduced prodigiosin-induced SKP2 repression.
      Prodigiosin also down-regulated E2F1 (mediates PI3K/PKB-induced SKP2
      transcription), but E2F1 overexpression failed to restore SKP2 expression in
      prodigiosin-treated cells. CONCLUSIONS AND IMPLICATIONS: Transcriptional
      repression of SKP2 and the consequent accumulation of p27(KIP1) are essential for
      prodigiosin's antiproliferative action. Mechanistically, prodigiosin induces PKB
      inhibition to down-regulate SKP2 in a GSK-3beta- and E2F1-independent manner. Our
      findings further implicate the potential for developing prodigiosin as a novel
      class of SKP2-targeting anticancer agent.

PMID- 22372493
TI  - Are my twins identical: parents may be misinformed by prenatal scan observations.

PMID- 22372494
TI  - Quorum activation at a distance: spatiotemporal patterns of gene regulation from
      diffusion of an autoinducer signal.
AB  - Quorum sensing (QS) bacteria regulate gene expression collectively by exchanging
      diffusible signal molecules known as autoinducers. Although QS is often studied
      in well-stirred laboratory cultures, QS bacteria colonize many physically and
      chemically heterogeneous environments where signal molecules are transported
      primarily by diffusion. This raises questions of the effective distance range of
      QS and the degree to which colony behavior can be synchronized over such
      distances. We have combined experiments and modeling to investigate the
      spatiotemporal patterns of gene expression that develop in response to a
      diffusing autoinducer signal. We embedded a QS strain in a narrow agar lane and
      introduced exogenous autoinducer at one terminus of the lane. We then measured
      the expression of a QS reporter as a function of space and time as the
      autoinducer diffused along the lane. The diffusing signal readily activates the
      reporter over distances of ~1 cm on time scales of ~10 h. However, the patterns
      of activation are qualitatively unlike the familiar spreading patterns of simple
      diffusion, as the kinetics of response are surprisingly insensitive to the
      distance the signal has traveled. We were able to reproduce these patterns with a
      mathematical model that combines simple diffusion of the signal with logistic
      growth of the bacteria and cooperative activation of the reporter. In a wild-type
      QS strain, we also observed the propagation of a unique spatiotemporal
      excitation. Our results show that a chemical signal transported only by diffusion
      can be remarkably effective in synchronizing gene expression over macroscopic
      distances.

PMID- 22372495
TI  - Effect of basic amino acids on photoreaction of ketoprofen in phosphate buffer
      solution.
AB  - Photoreaction of ketoprofen (KP), one of the widely used nonsteroidal anti
      inflammatory drugs (NSAIDs), was studied with transient absorption spectroscopy
      in phosphate buffer solution (pH 7.4) in the presence of basic amino acids of
      histidine (His), lysine (Lys) and arginine (Arg). Deprotonated form of KP (KP(-))
      excited with UV-light irradiation gave rise to carbanion through a
      decarboxylation reaction. It was found that carbanion abstracted a proton from
      the side chain of the protonated amino acids to yield 3-ethylbenzophenone ketyl
      biradical (EBPH); however, no reaction was observed with alanine. The relative
      yield of EBPH by the proton transfer reaction with His was ca. 40 times larger
      than that of the other two basic amino acids, suggesting that the proton-donating
      ability of His (protonated His) should be quite high. The information on the
      photoreaction mechanism of NSAIDs with basic amino acids was essential to
      understand primary reaction of excited NSAIDs in vivo causing photosensitization
      on human skin.

PMID- 22372496
TI  - Targeted therapies for pancreatic cancer.

PMID- 22372497
TI  - Novel therapeutic approaches in pancreatic cancer based on genomic alterations.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and devastating disease,
      which is characterized by invasiveness and dissemination to the lymphatic system
      and distant organs. In the absence of effective screening methods considerable
      efforts have thus been made to identify better systemic treatments than
      gemcitabine, the standard of care for advanced PDAC for well over a decade.
      However, until now only erlotinib, an epidermal growth-factor receptor tyrosine
      kinase inhibitor, has demonstrated a modest survival benefit in combination with
      gemcitabine in a phase III clinical trial. More recently, detailed global genomic
      analyses have provided a snapshot of the landscape of tumor genomes by showing
      that they contain four high frequency mutated genes and many low frequency
      mutated genes that correspond to 12 core signaling pathways. Strategies to target
      these frequently altered genes and their pathways, or low frequency mutated genes
      corresponding to the "personalized genome", offer novel therapeutic strategies.
      In the near future, the complete sequencing of the coding genome, together with
      the dramatically reduced costs of whole genome sequencing, will provide new
      opportunities to treat PDAC.

PMID- 22372498
TI  - Molecular mechanisms of pancreatic cancer dissemination: the role of the
      chemokine system.
AB  - Over the last decade it has been established that cancer-associated inflammation
      affects many aspects of malignancy and in particular endorses tumor cell
      survival, proliferation and distant spread. Chemokines and their receptors are
      major players of the cancerrelated inflammation. Our understanding of the
      chemokine role in tumor biology now ranges from their ability to recruit blood
      leukocytes within tumors, to direct effects on cancer cell survival,
      metastatization and regulation of angiogenesis. Chemokines and their receptors
      are expressed in human pancreatic adenocarcinoma and are involved in its
      malignant behavior. Notably, the receptor CX3CR1 favors tumor perineural tropism
      which is typical of this neoplasm and is associated with early recurrence after
      surgery and with poor patient prognosis.

PMID- 22372499
TI  - Mucin-based targeted pancreatic cancer therapy.
AB  - The prognosis of pancreatic cancer (PC) patients is very poor with a five-year
      survival of less than 5%. One of the major challenges in developing new therapies
      for PC is the lack of expression of specific markers by pancreatic tumor cells.
      Mucins are heavily Oglycosylated proteins characterized by the presence of short
      stretches of amino acid sequences repeated several times in tandem. The
      expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly
      upregulated in PC. Recent studies have also demonstrated a link between the
      aberrant expression and differential overexpression of mucin glycoproteins to the
      initiation, progression, and poor prognosis of the disease. These studies have
      led to increasing recognition of mucins as potential diagnostic markers and
      therapeutic targets in PC. In this focused review we present an overview of the
      therapies targeting mucins in PC, including immunotherapy (i.e. vaccines,
      antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic
      strategies.

PMID- 22372500
TI  - Therapeutic potential of perineural invasion, hypoxia and desmoplasia in
      pancreatic cancer.
AB  - Pancreatic cancer is one of the most fatal human malignancies. Though a
      relatively rare malignancy, it remains one of the deadliest tumors, with an
      extremely high mortality rate. The prognosis of patients with pancreatic cancer
      remains poor; only patients with small tumors and complete resection have a
      chance of a complete cure. Pancreatic cancer responds poorly to conventional
      therapies, including chemotherapy and irradiation. Tumor-specific targeted
      therapy is a relatively recent addition to the arsenal of anti-cancer therapies.
      It is important to find novel targets to distinguish tumor cells from their
      normal counterparts in therapeutic approaches. In the past few decades, studies
      have revealed the molecular mechanisms of pancreatic tumorigenesis, growth,
      invasion and metastasis. The proteins that participate in the pathophysiological
      processes of pancreatic cancer might be potential targets for therapy. This
      review describes the main players in perineural invasion, hypoxia and desmoplasia
      and the molecular mechanisms of these pathophysiological processes.

PMID- 22372503
TI  - Sp/KLF family and tumor angiogenesis in pancreatic cancer.
AB  - Tumor angiogenesis play a significant role in genesis, development and metastasis
      of pancreatic cancer though the process is different from angiogenesis in normal
      tissues. VEGF, one of the most important angiogenesis factors, is modulated by
      inflammation factors as well as transcriptional factors, such as members of
      Sp/KLF family. Recent research showed that VEGF related inflammation factors and
      Sp/KLF family members form a complex network structure, which causes genesis and
      development of tumor. Conceivably, fully understanding the mechanism linking VEGF
      related inflammation factors and Sp/KLF family members would promote the concept
      of tumor angiogenesis. Furthermore, it could also help to design effective
      strategies to target the key components of the network and control the
      development and progression of tumor.

PMID- 22372501
TI  - Targeting the cancer-stroma interaction: a potential approach for pancreatic
      cancer treatment.
AB  - Recent studies have demonstrated that the interaction between the cancer and the
      stroma, play a key role in the development of pancreatic cancer. The desmoplasia,
      which consists of fibroblasts, pancreatic stellate cells, lymphatic and vascular
      endothelial cells, immune cells, pathologic increased nerves, and the
      extracellular matrix (ECM), creates a complex tumor microenvironment that
      promotes pancreatic cancer development, invasion, metastasis, and resistance to
      chemotherapy. Thus, the potential approach for targeting the components of this
      desmoplastic reaction or the pancreatic tumor microenvironment might represent a
      novel therapeutic approach to advanced pancreatic carcinoma. Novel therapies that
      target on the pancreatic tumor microenvironment should become one of the more
      effective treatments for pancreatic cancer.

PMID- 22372504
TI  - Role of Wnt/beta-catenin signaling in drug resistance of pancreatic cancer.
AB  - Pancreatic cancer is characterized by its intrinsic resistance to cytotoxic
      agents. But the underlying molecular mechanism is unclear. Studies demonstrate
      that angiogenesis, presence of highly resistant cancer stem cells (CSCs),
      dysregulation of cell cycle and apoptosis are main aspects of mechanisms of
      pancreatic cancer chemoresistance. Interestingly, recent investigations of
      Wnt/beta-catenin signaling suggest roles for the signaling in these four aspects
      and the pathogenesis of pancreatic cancer. Conceivably, the dysregulation of
      Wnt/beta-catenin signaling pathway is involved in pancreatic cancer
      chemoresistance. Though researchers have proven it in some other cancer types,
      however, there is no direct evidence for this reasoning in pancreatic cancer.
      Designing effective experiment setups to define the function and mechanism of
      Wnt/beta-catenin signaling in pancreatic cancer chemoresistance and subsequently
      targeting the signaling to improve the sensitivity of chemotherapy in pancreatic
      cancer require a full understanding of the molecular mechanisms of Wnt/beta
      catenin signaling pathway in angiogenesis, maintaining of highly resistant CSCs,
      regulation of cell cycle and apoptosis in pancreatic cancer.

PMID- 22372505
TI  - Cytokine network: new targeted therapy for pancreatic cancer.
AB  - Increasing evidence has shown that cytokines have a role in tumor biology. The
      role of chemokines in tumor biology is important because these peptides may
      influence tumor growth, invasion, angiogenesis, and metastasis. In this review,
      we demonstrated the role of cytokines (Interleukin-1alpha, hepatocyte growth
      factor, Interleukin-8, stromal cell-derived factor-1 and CXC-chemokines/CXCR2
      biological axis) in pancreatic cancer angiogenesis, especially from the
      standpoint of the interaction between tumor and its microenvironments. The
      cytokines are intimately related with cancer angiogenesis. Blocking these
      cytokines could attenuate pancreatic cancer associated angiogenesis and further
      considered as a novel anti-angiogenic target in pancreatic cancer.

PMID- 22372506
TI  - Predicting secondary organic aerosol formation from terpenoid ozonolysis with
      varying yields in indoor environments.
AB  - The ozonolysis of terpenoids generates secondary organic aerosol (SOA) indoors.
      Models of varying complexity have been used to predict indoor SOA formation, and
      many models use the SOA yield, which is the ratio of the mass of produced SOA and
      the mass of consumed reactive organic gas. For indoor simulations, the SOA yield
      has been assumed as a constant, even though it depends on the concentration of
      organic particles in the air, including any formed SOA. We developed two indoor
      SOA formation models for single terpenoid ozonolysis, with yields that vary with
      the organic particle concentration. The models have their own strengths and were
      in agreement with published experiments for d-limonene ozonolysis. Monte Carlo
      analyses were performed, which simulated different residential and office
      environments to estimate ranges of SOA concentrations and yields for d-limonene
      and alpha-pinene ozonolysis occurring indoors. Results indicate that yields are
      highly variable indoors and are most influenced by background organic particles
      for steady-state formation and indoor ozone concentration for transient peak
      formation. Additionally, a review of ozonolysis yields for indoor-relevant
      terpenoids in the literature revealed much uncertainty in their values at low
      concentrations typical of indoors. PRACTICAL IMPLICATIONS: The results in this
      study suggest important factors that govern indoor secondary organic aerosol
      (SOA) formation and yields, in typical residential and office spaces. This
      knowledge informs the development and comparison of control strategies to reduce
      indoor-generated SOA. The ranges of SOA concentrations predicted indoors allow
      the quantification of the effects of sorptive interactions of semi-volatile
      organic compounds or reactive oxygen species with SOA, filter loading owing to
      SOA formation, and impacts of SOA on health, if links are established.

PMID- 22372502
TI  - Advances in biomarker research for pancreatic cancer.
AB  - Pancreatic cancer (PC) is a leading cause of cancer related deaths in United
      States. The lack of early symptoms results in latestage detection and a high
      mortality rate. Currently, the only potentially curative approach for PC is
      surgical resection, which is often unsuccessful because the invasive and
      metastatic nature of the tumor masses makes their complete removal difficult.
      Consequently, patients suffer relapses from remaining cancer stem cells or drug
      resistance that eventually lead to death. To improve the survival rate, the early
      detection of PC is critical. Current biomarker research in PC indicates that a
      serum carbohydrate antigen, CA 19-9, is the only available biomarker with
      approximately 90% specificity to PC. However, the efficacy of CA 19-9 for
      assessing prognosis and monitoring patients with PC remains contentious. Thus,
      advances in technology and the detection of new biomarkers with high specificity
      to PC are needed to reduce the mortality rate of pancreatic cancer.

PMID- 22372507
TI  - Myxoinflammatory fibroblastic sarcoma: report of a case and review of the
      literature.
AB  - Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade sarcoma generally
      arising in adults. We present a case of MIFS in a 5-year-old boy with a palpable
      nodule in the subcutaneous tissue of the scalp. We carried out a literature
      review to evaluate the diagnostic patterns based on histologic and cytologic
      features and possible pitfalls and misdiagnoses. A systematic search for articles
      of interest published between 1995 and 2011 was performed in MEDLINE and PubMed
      using the words "myxoinflammatory fibroblastic sarcoma," "myxohyaline tumor," and
      "inflammatory myxoid tumor." Histology and cytology have a pivotal role in the
      differential diagnosis between MIFS and other potential soft-tissue mimics, such
      as nodular and proliferative fasciitis and inflammatory myofibroblastic tumor.
      Fine-needle aspiration cytology is a safe and useful tool for the diagnosis of
      pediatric patients with MIFS and is important for an accurate and precise
      preoperative workup to optimize subsequent management and treatment.

PMID- 22372508
TI  - Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide
      combination in treating stage 2 hypertensive patients.
AB  - OBJECTIVE: The objective of this study was to assess the effects of valsartan or
      olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ)
      in the treatment of stage 2 hypertension. RESEARCH DESIGN AND METHODS: 180
      patients with diastolic blood pressure (DBP) >= 99 and < 110 mm Hg were treated
      with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients
      whose blood pressure (BP) was not controlled, were randomized to the combination
      of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg +
      amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks. MAIN OUTCOME MEASURES: At the end of
      each period, clinical and ambulatory BP measurements were recorded. RESULTS: Both
      triple combinations produced greater ambulatory and clinical SBP/DBP reduction
      than dual therapy. However, mean reduction from baseline in the valsartan +
      amlodipine + HCTZ-treated patients was significantly greater than in the
      olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the
      add-on effect of valsartan was significantly greater than that of olmesartan, the
      difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 -
      3.51)/3.0 (95% CI 0.59 - 3.34) mm Hg, p < 0.01). CONCLUSIONS: The addition of
      valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of
      olmesartan.

PMID- 22372509
TI  - Production and characterization of plutonium dioxide particles as a quality
      control material for safeguards purposes.
AB  - Plutonium (Pu) dioxide particles were produced from certified reference material
      (CRM) 136 solution (CRM 136-plutonium isotopic standard, New Brunswick
      Laboratory, Argonne, IL, U.S.A., 1987) using an atomizer system on December 3,
      2009 after chemical separation of americium (Am) on October 27, 2009. The highest
      density of the size distribution of the particles obtained from 312 particles on
      a selected impactor stage was in the range of 0.7-0.8 MUm. The flattening degree
      of 312 particles was also estimated. The isotopic composition of Pu and uranium
      (U) and the amount of Am were estimated by thermal ionization mass spectrometry
      (TIMS), inductively coupled plasma mass spectrometry (ICPMS), and alpha
      spectrometry. Within uncertainties the isotopic composition of the produced
      particles is in agreement with the expected values, which were derived from the
      decay correction of the Pu isotopes in the CRM 136. The elemental ratio of Am to
      Pu in the produced particles was determined on the 317th and 674th day after Am
      separation, and the residual amount of Am in the  solution was estimated. The
      analytical results of single particles by micro-Raman-scanning electron
      microscopy (SEM)-energy-dispersive X-ray spectrometry (EDX) indicate that the
      produced particles are Pu dioxide. Our initial attempts to measure the density of
      two single particles gave results with a spread value accompanied by a large
      uncertainty.

PMID- 22372510
TI  - Highly active and durable core-corona structured bifunctional catalyst for
      rechargeable metal-air battery application.
AB  - A new class of core-corona structured bifunctional catalyst (CCBC) consisting of
      lanthanum nickelate centers supporting nitrogen-doped carbon nanotubes (NCNT) has
      been developed for rechargeable metal-air battery application. The nanostructured
      design of the catalyst allows the core and corona to catalyze the oxygen
      evolution reaction (OER) and oxygen reduction reaction (ORR), respectively. These
      materials displayed exemplary OER and ORR activity through half-cell testing,
      comparable to state of the art commercial lanthanum nickelate (LaNiO(3)) and
      carbon-supported platinum (Pt/C), with added bifunctional capabilities allowing
      metal-air battery rechargeability. LaNiO(3) and Pt/C are currently the most
      accepted benchmark electrocatalyst materials for the OER and ORR, respectively;
      thus with comparable activity toward both of these reactions, CCBC are presented
      as a novel, inexpensive catalyst component for the cathode of rechargeable metal
      air batteries. Moreover, after full-range degradation testing (FDT) CCBC retained
      excellent activity, retaining 3 and 13 times greater ORR and OER current upon
      comparison to state of the art Pt/C. Zinc-air battery performances of CCBC is in
      good agreement with the half-cell experiments with this bifunctional
      electrocatalyst displaying high activity and stability during battery discharge,
      charge, and cycling processes. Owing to its outstanding performance toward both
      the OER and ORR, comparable with the highest performing commercial catalysts to
      date for each of the respective reaction, coupled with high stability and
      rechargeability, CCBC is presented as a novel class of bifunctional catalyst
      material that is very applicable to future generation rechargeable metal-air
      batteries.

PMID- 22372511
TI  - In vitro phosphorylation of the focal adhesion targeting domain of focal adhesion
      kinase by Src kinase.
AB  - Focal adhesion kinase (FAK), a key regulator of cell adhesion and migration, is
      overexpressed in many types of cancer. The C-terminal focal adhesion targeting
      (FAT) domain of FAK is necessary for proper localization of FAK to focal
      adhesions and subsequent activation. Phosphorylation of Y926 in the FAT domain by
      the tyrosine kinase Src has been shown to promote metastasis and invasion in vivo
      by linking the FAT domain to the MAPK pathway via its interaction with growth
      factor receptor-bound protein 2. Several groups have reported that inherent
      conformational dynamics in the FAT domain likely regulate phosphorylation of
      Y926; however, what regulates these dynamics is unknown. In this paper, we
      demonstrate that there are two sites of in vitro Src-mediated phosphorylation in
      the FAT domain: Y926, which has been shown to affect FAK function in vivo, and
      Y1008, which has no known biological role. The phosphorylation of these two
      tyrosine residues is pH-dependent, but this does not reflect the pH dependence of
      Src kinase activity. Circular dichroism and nuclear magnetic resonance data
      indicate that the stability and conformational dynamics of the FAT domain are
      sensitive to changes in pH over a physiological pH range. In particular, regions
      of the FAT domain previously shown to regulate phosphorylation of Y926 as well as
      regions near Y1008 show pH-dependent dynamics on the microsecond to millisecond
      time scale.

PMID- 22372512
TI  - A phase 2a randomized, parallel group, dose-ranging study of molindone in
      children with attention-deficit/hyperactivity disorder and persistent, serious
      conduct problems.
AB  - OBJECTIVE: To evaluate safety and tolerability of four doses of immediate-release
      molindone hydrochloride in children with attention-deficit/hyperactivity disorder
      (ADHD) and serious conduct problems. METHODS: This open-label, parallel-group,
      dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD
      and persistent, serious conduct problems to receive oral molindone thrice daily
      for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight <30 kg),
      group 2-20 mg (10 mg if <30 kg), group 3-30 mg (15 mg if <30 kg), and group 4-40
      mg (20 mg if <30 kg). The primary outcome measure was to evaluate safety and
      tolerability of molindone in children with ADHD and serious conduct problems.
      Secondary outcome measures included change in Nisonger Child Behavior Rating Form
      Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change
      in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale
      scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale
      revised (SNAP-IV) ADHD-related subscale scores. RESULTS: The study randomized 78
      children; 55 completed the study. Treatment with molindone was generally well
      tolerated, with no clinically meaningful changes in laboratory or physical
      examination findings. The most common treatment-related adverse events (AEs)
      included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation
      (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body
      mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs
      increased with increasing dose. NCBRF-TIQ subscale scores improved in all four
      treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups
      1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all
      treatment groups, and CGI-I scores improved to the greatest degree in group 4.
      CONCLUSIONS: Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20
      40 mg (>= 30 kg) was well tolerated, and preliminary efficacy results suggest
      that molindone produces dose-related behavioral improvements over 9-12 weeks.
      Additional double-blind, placebo-controlled trials are needed to further
      investigate molindone in this pediatric population.

PMID- 22372513
TI  - Adverse events in medication treatment-naive children with attention
      deficit/hyperactivity disorder: results from a small, controlled trial of
      lisdexamfetamine dimesylate.
AB  - OBJECTIVE: To evaluate the type, frequency, duration, and severity of treatment
      emergent adverse events (TEAEs) of the prodrug lisdexamfetamine dimesylate (LDX)
      in children with and without previous exposure to stimulant medication in the
      treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: This
      single-blind, modified laboratory school study used open-label, dose optimization
      of children aged 6-12 years. LDX, initiated at 30 mg, was dose titrated in 20 mg
      increments to a possible 70 mg over 4-5 weeks. Safety was assessed using adverse
      effects and LDX levels. RESULTS: Twenty-eight subjects enrolled in the study,
      with 27 safety protocol completers (n=14 previous stimulant exposure; n=13
      stimulant naive). The stimulant-naive group reported more trouble sleeping,
      stomach pain, and hyperfocus, but only previous-exposure subjects experienced
      dizziness. Previous-exposure subjects showed trends of more decreased appetite,
      less talkativeness, and less lip sucking. There were no differences in the mean
      duration of TEAEs. The epidemiological method of percent person-weeks applied to
      ADHD treatment offers a novel approach to interpreting the pattern of TEAEs.
      CONCLUSION: LDX reduced the core symptoms of ADHD with more severe adverse events
      in stimulant-naive than previous-exposure subjects. Future controlled studies
      with larger samples should address the impact of previous stimulant exposure on
      other ADHD treatments.

PMID- 22372514
TI  - Comparison of long-term (at least 24 weeks) weight gain and metabolic changes
      between adolescents and adults treated with olanzapine.
AB  - OBJECTIVE: The purpose of these analyses was to compare the weight and other
      metabolic changes between adolescents and adults during long-term (at least 24
      weeks) olanzapine treatment. METHOD: The adult database included 86 studies with
      12,425 patients with schizophrenia, schizoaffective disorder, depression,
      borderline personality disorder, or bipolar I disorder; the adolescent database
      comprised six studies with 489 patients with schizophrenia, schizoaffective
      disorder, borderline personality disorder, bipolar I disorder, or prodromal
      psychosis. Patients who had at least 24 weeks of olanzapine exposure (N=4,280
      from adult database and N=179 from adolescent database) were analyzed in this
      study. Weight data were collected for all patients, fasting glucose and lipids
      data were collected in some patients. For weight gain, data in 34.5% adults
      (4,280/12,425) and 36.6% adolescents (179/489) were analyzed while for glucose
      and lipids, data in 8.4% (1,038/12,425) adults and 24.9% adolescents (122/489)
      were analyzed. Adult patients were treated with oral (5-20 mg/day) or depot
      formulations (doses equivalent to oral doses of 5-20 mg/day) of olanzapine and
      adolescent patients were treated with oral olanzapine (2.5-20 mg/day). The
      incidences of potentially clinically significant categorical changes in weight
      and metabolic parameters were calculated with a 95% confidence interval (CI).
      Nonoverlapping 95% CIs were considered as indicating a statistically significant
      difference. Weight, lipid, and glucose change comparisons are summarized.
      RESULTS: The mean age for adolescents and adults was 15.8 and 38.8, respectively.
      The percentage of the male population was similar for both adults (58.5%) and
      adolescents (62.8%). The median duration of the follow-up period was 201 days for
      adolescent database and 280 days for adult database. The mean weight gain from
      baseline to endpoint in adolescents was 11.24 kg when compared with 4.81 kg in
      adults. The 95% CI for adolescents (10.1, 12.4) and adults (4.57, 5.04) are not
      overlapping, which indicates that the difference between adolescents and adults
      is statistically significant. The percentage of olanzapine-treated adolescents
      with >= 7% mean weight gain was 89.4% compared with 55.4% in adults (Number need
      to harm [NNH]=3). Mean changes from baseline to endpoint were also greater for
      adolescents than for adults in fasting total cholesterol (5.49 mg/dL vs. 2.06
      mg/dL), LDL (5.41 mg/dL vs. 0.49 mg/dL), and triglycerides (20.49 mg/dL vs. 16.72
      mg/dL), but overlapping 95% CIs were observed for all lipid parameters. Mean
      changes from baseline to endpoint in fasting glucose values were similar between
      adolescents and adults (3.13 mg/dL vs. 3.95 mg/dL). However, the incidence of
      treatment-emergent significant glucose changes was greater in adults. Among
      olanzapine-treated adults and adolescents, 8.9% and 0.9% experienced a shift from
      normal to high and 12.5% and 3.3% experienced a shift from normal/impaired
      glucose tolerance (IGT) to high fasting glucose, respectively. The incidence of
      IGT to high elevations in glucose was greater in adolescents, but overlapping 95%
      CI was observed. CONCLUSIONS: The types of metabolic changes during the long-term
      olanzapine treatment in adolescents were similar to those observed in adults.
      However, the magnitude of changes in weight and lipid parameters was greater in
      adolescents. Patients should receive regular monitoring of weight, fasting blood
      glucose, and lipid profile at the beginning of, and periodically during,
      treatment with olanzapine.

PMID- 22372515
TI  - How many maternal deaths are there in Portugal?
AB  - INTRODUCTION: Maternal mortality is a public health issue, internationally
      considered an indicator of women's status in society, indirectly translating
      access to health facilities. However, it is difficult to measure and is usually
      underestimated by official records. METHODS: Maternal deaths missed by the
      official statistics in Portugal between 2001 and 2006 were estimated by multiple
      recapture methods using three different data sources. An upper limit to the
      number of deaths was derived from the application of the mortality function of
      women in reproductive age to the estimated annual number of pregnancies. RESULTS:
      Maternal mortality decreased from 40 to less than 10 deaths per 100,000 live
      births between 1978 and 1986. Between 2001 and 2006, it varied from 2.5 to 19 and
      was underestimated by 9%-26%. Nevertheless, within the same age range, the risk
      of a pregnant women to die was four times less than a women in the general
      population. CONCLUSION: Like in other developed countries, official statistics in
      Portugal have systematically underestimated maternal deaths. These deaths are a
      rare event, but the consistent increase in the average age at pregnancy may
      exacerbate the main causes of death, raising concerns for the future and
      prompting the need for emergency facilities nearby maternities.

PMID- 22372516
TI  - A retrospective analysis of the management of freckles and lentigines using four
      different pigment lasers on Asian skin.
AB  - BACKGROUND: The risk of post-inflammatory hyperpigmentation (PIH) is increased
      during freckles and lentigines treatment in Asians. OBJECTIVE: To determine the
      effectiveness and safety of using 595-nm long pulsed dye laser (LPDL), 755-nm LP
      Alexandrite laser, 532-nm QS Nd:YAG laser and 532-nm LP potassium-titanyl
      phosphate (KTP) laser for the treatment of freckles or lentigines in Asian
      patients. METHODS: This is a retrospective study of 40 Chinese patients, who were
      divided into four groups based on treatment modality using four different pigment
      lasers. Each patient attended between 1 and 4 treatments (mean of 1.8), at 4-6
      weeks intervals, depending on clinical response. Lesional clearance and PIH were
      assessed by two independent clinicians. RESULTS: Statistically significant
      improvement of global and focal facial pigmentation was found after treatment
      with LPDL, QS Nd:YAG and LP KTP lasers. No significant improvement was found
      after LP Alexandrite laser. PIH risk was 20% after LP Alexandrite treatment, 10%
      with QS Nd:YAG, and absent after LPDL and LP KTP treatment. CONCLUSION: A long
      pulse laser and small spot size appear to reduce the risks of lentigines
      treatment in darker skin types.

PMID- 22372517
TI  - Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic
      treatment with 25 mg diclofenac-K liquid capsules.
AB  - BACKGROUND: Diclofenac-potassium (diclofenac--K) 25 mg liquid capsule is absorbed
      more quickly than the tablet formulation. It offers potential for rapid pain
      relief, but may alter gastro-duodenal tolerability. AIM: To evaluate the gastro
      duodenal tolerance of diclofenac-K 25 mg liquid capsules vs. diclofenac-K 12.5 mg
      tablets, acetylsalicylic acid (ASA) 500 mg tablets and ibuprofen 200 mg liquid
      capsules. METHODS: In an endoscopist-blinded, randomised, parallel-group study,
      volunteers received 15 doses of diclofenac-K 25 mg liquid capsules (n = 36),
      diclofenac-K 2 * 12.5 mg tablets (n = 36), ibuprofen 2 * 200 mg liquid capsules
      (n = 24) or ASA 2 * 500 mg tablets (n = 36) over 5 days. The primary outcome was
      the incidence of erosive gastro-duodenal lesions at Day 6. Secondary outcomes
      included modified Lanza score and change in gastric mucosal prostaglandin
      synthesis. RESULTS: The lowest incidence of erosive gastro-duodenal lesions was
      with diclofenac-K liquid capsules (53%), compared to 61% with diclofenac-K
      tablets (P = 0.52), 75% with ibuprofen (P = 0.08) and 94% with ASA (P = 0.001).
      Results were similar for the Lanza scores, although diclofenac-K liquid capsules
      were significantly superior to ibuprofen liquid capsules (P = 0.04). Diclofenac-K
      liquid capsules inhibited prostaglandin synthesis by 52% compared to 64% for
      diclofenac-K tablets (P = 0.10), 50% for ibuprofen (P = 0.85) and 79% for ASA (P
      = 0.002). With respect to safety, adverse events were most frequent in the ASA
      group, predominantly gastrointestinal events. CONCLUSIONS: Mucosal injury with
      diclofenac-K liquid 25 mg liquid capsules was similar to diclofenac-K 25 mg
      tablets, significantly lower than ASA 1 g tablets and showed some superiority
      over ibuprofen 400 mg liquid capsules (EudraCT Number 2009-011278-14).

PMID- 22372518
TI  - Substrate and metal control of barrier heights for oxo transfer to Mo and W bis
      dithiolene sites.
AB  - Reaction coordinates for oxo transfer from the substrates Me(3)NO, Me(2)SO, and
      Me(3)PO to the biologically relevant Mo(IV) bis-dithiolene complex
      [Mo(OMe)(mdt)(2)](-) where mdt = 1,2-dimethyl-ethene-1,2-dithiolate(2-), and from
      Me(2)SO to the analogous W(IV) complex, have been calculated using density
      functional theory. In each case, the reaction first proceeds through a transition
      state (TS1) to an intermediate with substrate weakly bound, followed by a second
      transition state (TS2) around which breaking of the substrate X-O bond begins. By
      analyzing the energetic contributions to each barrier, it is shown that the
      nature of the substrate and metal determines which transition state controls the
      rate-determining step of the reaction.

PMID- 22372519
TI  - The impact of sirolimus on sex hormones in male adolescent kidney recipients.
AB  - While it is known that sirolimus affects sex hormones in adult kidney transplant
      patients, there is a scarcity of data on its effects on sex hormone levels in
      adolescent kidney recipients. The objective of this study is to describe the
      impact of sirolimus on the sex hormones in this patient population. This is a
      retrospective review of male adolescent renal transplant patients transitioned to
      sirolimus. Baseline and subsequent annual testosterone levels were collected.
      Linear regression was undertaken to determine the predictors of testosterone
      levels. Four African Americans and 11 Caucasians, median age of 15 yr (11-18) in
      2008, were included. Mean time post-transplant was 81 +/- 37 months. Mean
      testosterone values were the following: 336 +/- 135 ng/dL (n = 8) at baseline,
      349 +/- 130 ng/dL (n = 15) one yr later, and 360 +/- 132 ng/dL (n = 13) two yr
      later (normal range for adult males: 350-970 ng/dL). Seven (47%) patients
      experienced a decrease in testosterone levels. Time on sirolimus was associated
      with decreased testosterone (r = 0.643, p = 0.010). Testosterone levels in
      pubertal male kidney transplant recipients on sirolimus may be suppressed,
      especially if they have been treated with sirolimus for several years. These data
      need to be confirmed in a larger study.

PMID- 22372520
TI  - Evaluation of a drop-in rolling-group model of support to stop smoking.
AB  - AIMS: To assess longer-term outcomes of a drop-in rolling-group model of
      behavioural support for smoking cessation and the factors that influence
      cessation outcomes. DESIGN: Prospective observational cohort study. SETTING: Fag
      Ends NHS Stop Smoking Service in Liverpool and Knowsley, UK. PARTICIPANTS: A
      total of 2585 clients, aged 16 or over, setting a quit date. MEASUREMENTS:
      Routine monitoring data were collected from Fag Ends service users and were
      supplemented by survey data on socio-economic circumstances, smoking-related
      behaviour and self-report and carbon monoxide (CO)-validated smoking status at 52
      week follow-up. FINDINGS: The CO-validated prolonged abstinence rate at 52 weeks
      for smokers attending the groups was 5.6%, compared with 30.7% at 4 weeks (a
      relapse rate of 78.2%). The sample was particularly disadvantaged: 68% resided in
      the most deprived decile of the English Index of Multiple Deprivation. Higher
      socio-economic status within the sample was a predictor of quitting. Other
      predictors of long-term cessation in multivariate analysis included older age,
      being female, lower levels of nicotine dependence, having a live-in partner,
      stronger determination to quit and use of varenicline versus other medication.
      CONCLUSIONS: A wholly state-reimbursed clinical stop-smoking service providing
      behavioural support and medication in a region of high economic and social
      disadvantage has reached a significant proportion of the smoking population. Long
      term success rates are lower than are found typically in clinical trials, but
      higher than would be expected if the smokers were to try and quit unaided.
      Research is needed into how to improve on the success rates achieved.

PMID- 22372521
TI  - Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and
      peritoneum).
AB  - Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and
      peritoneum) Ovarian serous carcinoma (OSC) is the most common of the ovarian
      epithelial malignancies, and accounts for most of the mortality. Traditionally,
      ovarian cancer has been considered to be one disease; however, it is now apparent
      that it actually consists of many different entities. OSC can be further
      segregated into two processes: high-grade serous carcinoma (HGSC) and low-grade
      serous carcinoma. This classification is supported by molecular changes,
      morphological appearance, clinical behaviour, and distinct precursor lesions.
      This review will describe in detail these features of OSC, differential
      diagnosis, prognosis, and recent challenges to the existing hypotheses regarding
      the origin of these tumours. Special attention will be paid to HGSC and its
      relationship with BRCA abnormalities, especially those seen in hereditary breast
      and ovarian cancer syndrome. Finally, treatment options based on specific
      molecular targets will be discussed.

PMID- 22372522
TI  - Diabetes as a risk factor for dementia and mild cognitive impairment: a meta
      analysis of longitudinal studies.
AB  - This study examined the association of diabetes with the onset of dementia
      (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) and
      mild cognitive impairment (MCI) by using a quantitative meta-analysis of
      longitudinal studies. EMBASE and MEDLINE were searched for articles published up
      to December 2010. All studies that examined the relationship between diabetes and
      the onset of dementia or MCI were included. Pooled relative risks were calculated
      using fixed and random effects models. Nineteen studies met our inclusion
      criteria for this meta-analysis, and 6184 subjects with diabetes and 38 530
      subjects without diabetes were included respectively. All subjects were without
      dementia or MCI at baseline. The quantitative meta-analysis showed that subjects
      with diabetes had higher risk for AD (relative risk (RR):1.46, 95% confidence
      interval (CI): 1.20-1.77), VD (RR: 2.48, 95% CI: 2.08-2.96), any dementia (RR:
      1.51, 95% CI: 1.31-1.74) and MCI (RR: 1.21, 95% CI: 1.02-1.45) than those
      without. The quantitative meta-analysis showed that diabetes was a risk factor
      for incident dementia (including AD, VD and any dementia) and MCI.

PMID- 22372523
TI  - Metformin reduces vascular production of vasoconstrictor prostanoids in fructose
      overloaded rats.
AB  - Metformin is a hypoglycaemic drug currently used to increase insulin sensitivity
      in the treatment of type 2 diabetes and metabolic syndrome. Its main mechanism of
      action is through activation of AMP-activated protein kinase, an enzyme that
      regulates cellular and whole organ metabolism. The fructose-overloaded rat is an
      experimental model with features that resemble human metabolic syndrome. We have
      previously reported alterations in vascular prostanoids (PR) in this model. The
      aim of this study was to analyse the effects of metformin treatment on blood
      pressure, metabolic parameters and PR production in aorta and mesenteric vascular
      bed (MVB) from fructose-overloaded animals. Four groups of male Sprague-Dawley
      rats were used: control, fructose overloaded (10% w/v fructose), metformin
      treated (50 mg kg(-1) day(-1) ) and fructose-overloaded treated with metformin.
      Rats with fructose overload had significantly elevated systolic blood pressure,
      glycaemia, triglyceridaemia, cholesterolaemia and insulinaemia compared with
      controls. Except for insulinaemia, metformin limited all these increases in
      fructose-overloaded animals. Fructose overload reduced prostacyclin levels in
      aorta and MVB, but prostaglandin E(2) levels were only reduced in MVB. Metformin
      treatment reduced the levels of the vasoconstrictor prostaglandins, PGF(2) alpha
      and thromboxane, in both vascular preparations from fructose-overloaded rats.
      PGF(2) alpha levels were significantly reduced by metformin in controls. In
      conclusion, one of the mechanisms by which metformin reduced blood pressure in
      this model is by decreasing vasoconstrictor prostaglandin production.

PMID- 22372524
TI  - Energy transfer from poly(vinyl carbazole) to a fluorene-vinylene copolymer in
      solution and in the solid state.
AB  - This article reports a comparative study of the energy transfer processes in
      solution and the solid state from poly(vinyl carbazole; the donor) to
      dimethylphenyl-terminated poly[(9,9-dioctylfluorenyl-2,7-divinylene-fluorene)-co
      alt-{2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene}] (the acceptor). The results in
      solutions suggest that a decrease of the donor emission intensity with an
      increasing acceptor concentration is more closely related to the trivial energy
      transfer process, indicating that the donor and acceptor chains are not in close
      contact during the lifetime of the donor excited state. This conclusion was
      reached using the amplitude-averaged lifetime of the donor, which is practically
      independent of the acceptor concentration. In the solid state, the polymer blends
      showed a decrease in the donor emission with an increasing acceptor
      concentration, and a decrease in the donor lifetime was also observed. Thus, in
      the solid state, changes in morphology interfere with the nonradiative resonant
      energy transfer process, but influence on the trivial process cannot be
      completely neglected. The lifetime does not follow a continuous decrease with the
      PFO-MEHPV concentration like the emission intensity does. The changes in the
      lifetime values occur over the same concentration range as do the changes of
      morphology, as shown by the scanning electron micrographs.

PMID- 22372525
TI  - Phylloquinone (vitamin K(1) ) biosynthesis in plants: two peroxisomal
      thioesterases of Lactobacillales origin hydrolyze 1,4-dihydroxy-2-naphthoyl-CoA.
AB  - It is not known how plants cleave the thioester bond of 1,4-dihydroxy-2-naphthoyl
      CoA (DHNA-CoA), a necessary step to form the naphthoquinone ring of phylloquinone
      (vitamin K(1) ). In fact, only recently has the hydrolysis of DHNA-CoA been
      demonstrated to be enzyme driven in vivo, and the cognate thioesterase
      characterized in the cyanobacterium Synechocystis. With a few exceptions in
      certain prokaryotic (Sorangium and Opitutus) and eukaryotic (Cyanidium,
      Cyanidioschyzon and Paulinella) organisms, orthologs of DHNA-CoA thioesterase are
      missing outside of the cyanobacterial lineage. In this study, genomic approaches
      and functional complementation experiments identified two Arabidopsis genes
      encoding functional DHNA-CoA thioesterases. The deduced plant proteins display
      low percentages of identity with cyanobacterial DHNA-CoA thioesterases, and do
      not even share the same catalytic motif. GFP-fusion experiments demonstrated that
      the Arabidopsis proteins are targeted to peroxisomes, and subcellular
      fractionations of Arabidopsis leaves confirmed that DHNA-CoA thioesterase
      activity occurs in this organelle. In vitro assays with various aromatic and
      aliphatic acyl-CoA thioester substrates showed that the recombinant Arabidopsis
      enzymes preferentially hydrolyze DHNA-CoA. Cognate T-DNA knock-down lines display
      reduced DHNA-CoA thioesterase activity and phylloquinone content, establishing in
      vivo evidence that the Arabidopsis enzymes are involved in phylloquinone
      biosynthesis. Extraordinarily, structure-based phylogenies coupled to comparative
      genomics demonstrate that plant DHNA-CoA thioesterases originate from a
      horizontal gene transfer with a bacterial species of the Lactobacillales order.

PMID- 22372526
TI  - Effects of pulsed electric fields on the bioactive compound content and
      antioxidant capacity of tomato fruit.
AB  - The effect of moderate intensity pulsed electric fields (MIPEF) on the bioactive
      compounds (total polyphenol, lycopene, and vitamin C content) as well as on the
      antioxidant capacity of tomato fruit was studied. The MIPEF treatment conditions
      were optimized to obtain tomato fruit with a high content of bioactive compounds.
      Tomato fruits were subjected to different electric field strengths (from 0.4 to
      2.0 kV/cm) and number of pulses (from 5 to 30) and then immediately refrigerated
      at 4  degrees C for 24 h. A concentration of bioactive compounds higher than that
      of untreated tomatoes was obtained in MIPEF-treated tomatoes. A 44% increase in
      total polyphenol content was achieved under 30 pulses at 1.2 kV/cm. The
      hydrophilic antioxidant capacity was also enhanced by 44% applying 18 pulses at
      1.2 kV/cm, and the lipophilic antioxidant capacity was increased by 37% under 5
      pulses at 1.2 kV/cm. The maximum overall level of bioactive compounds and
      antioxidant capacity in the treated tomatoes was obtained under 16 pulses at 1
      kV/cm. Therefore, MIPEF treatments could be considered an effective method to
      enhance the bioactive compound content and antioxidant potential of tomatoes.

PMID- 22372527
TI  - ET-1 actions in the kidney: evidence for sex differences.
AB  - Hypertension and chronic kidney disease are more common in men than in
      premenopausal women at the same age. In animal models, females are relatively
      protected against genetic or pharmacological procedures that produce high blood
      pressure and renal injury. Overactivation or dysfunction of the endothelin (ET)
      system modulates the progression of hypertension or kidney diseases with the
      ET(A)  receptor primarily mediating vasoconstriction, injury and anti
      natriuresis, and ET(B)  receptors having opposite effects. The purpose of this
      review is to examine the role of the ET system in the kidney with a focus on the
      inequality between the sexes associated with the susceptibility to and
      progression of hypertension and kidney diseases. In most animal models, males
      have higher renal ET-1 mRNA expression, greater ET(A) -mediated responses,
      including renal medullary vasoconstriction, and increased renal injury. These
      differences are reduced following gonadectomy suggesting a role for sex hormones,
      mainly testosterone. In contrast, females are relatively protected from high
      blood pressure and kidney damage via increased ET(B)  versus ET(A)  receptor
      function. Furthermore, ET(A)  receptors may have a favourable effect on sodium
      excretion and reducing renal damage in females. In human studies, the genetic
      polymorphisms of the ET system are more associated with hypertension and renal
      injury in women. However, the knowledge of sex differences in the efficacy or
      adverse events of ET(A)  antagonists in the treatment of hypertension and kidney
      disease is poorly described. Increased understanding how the ET system acts
      differently in the kidneys between sexes, especially with regard to receptor
      subtype function, could lead to better treatments for hypertension and renal
      disease. LINKED ARTICLES This article is part of a themed section on Endothelin.
      To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2013.168.issue-1.

PMID- 22372528
TI  - Continuous regional myocardial blood flow measurement: validation of a near
      infrared laser Doppler device in a porcine model.
AB  - OBJECTIVE: RMBF measurement is a major concern in various clinical and
      experimental settings, but no validated device for RMBF is currently available.
      METHODS:   An LVP-triggered laser Doppler to measure RMBF was validated by
      simultaneous fluorescent MS RMBF in a porcine LAD flow reduction model (n = 10
      pigs). The laser probe was positioned on the left ventricle's anterior wall. LAD
      blood flow reduction was achieved by a shaft-driven occluder positioned proximal
      to the transit-time flow meter measuring coronary blood flow. RMBF was measured
      at baseline; after the reduction of LAD blood flow to 70% and 30% of baseline; at
      20 and 120 minutes of reperfusion; and, finally, 15 minutes after LAD occlusion.
      RESULTS: Laser Doppler RMBF (LDU) correlated strongly with MS RMBF under all
      tested conditions: baseline (epicardial 194.7 +/- 41.9, endocardial 130.2 +/-
      29.2); 70% baseline-flow (epicardial 160.4 +/- 27.7, endocardial 112.1 +/- 15.1);
      30% baseline-flow (epicardial 44.3 +/- 5.5, endocardial 32.9 +/- 9); 20 minutes
      reperfusion (epicardial 175.8 +/- 33.6, endocardial 126.5 +/- 30); 120 minutes
      reperfusion (epicardial 146.3 +/- 31.1, endocardial 107.1 +/- 29.7); and complete
      LAD occlusion (epicardial 10.5 +/- 5.8 endocardial 1.4 +/- 0.3) (r = 0.986-0.962,
      p < 0.001). CONCLUSIONS: This new blood pressure waveform-triggered laser Doppler
      probe is able to measure RMBF at different depths online in the beating heart.

PMID- 22372529
TI  - Highly conductive and porous activated reduced graphene oxide films for high
      power supercapacitors.
AB  - We present a novel method to prepare highly conductive, free-standing, and
      flexible porous carbon thin films by chemical activation of reduced graphene
      oxide paper. These flexible carbon thin films possess a very high specific
      surface area of 2400 m(2) g(-1) with a high in-plane electrical conductivity of
      5880 S m(-1). This is the highest specific surface area for a free-standing
      carbon film reported to date. A two-electrode supercapacitor using these carbon
      films as electrodes demonstrated an excellent high-frequency response, an
      extremely low equivalent series resistance on the order of 0.1 ohm, and a high
      power delivery of about 500 kW kg(-1). While higher frequency and power values
      for graphene materials have been reported, these are the highest values achieved
      while simultaneously maintaining excellent specific capacitances and energy
      densities of 120 F g(-1) and 26 W h kg(-1), respectively. In addition, these free
      standing thin films provide a route to simplify the electrode-manufacturing
      process by eliminating conducting additives and binders. The synthetic process is
      also compatible with existing industrial level KOH activation processes and roll
      to-roll thin-film fabrication technologies.

PMID- 22372530
TI  - New insights into the versatile roles of platelet FlnA.
AB  - Recent findings have identified critical roles for the actin filament
      crosslinking protein filamin A (FlnA) in platelets and megakaryocytes. This short
      review focuses on the structure of FlnA and its interaction with the Von
      Willebrand Factor receptor GPIb-IX-V complex and the fibrinogen receptor, the
      integrin alphaIIbbeta3 in platelets.

PMID- 22372531
TI  - A prospective randomized trial comparing the recovery of platelet function after
      loading dose administration of prasugrel or clopidogrel.
AB  - Prasugrel results in greater platelet inhibition compared to clopidogrel which
      may prolong the time to platelet P2Y(12) receptor function recovery following
      drug cessation after loading dose (LD) administration. This randomized study
      assessed the time to recovery of platelet function in patients with coronary
      artery disease after a LD of prasugrel or clopidogrel. Enrolled patients (n = 21)
      received either prasugrel (30 mg or 60 mg) or clopidogrel (600 mg) in preparation
      for coronary angiography. Platelet function was assessed by the VerifyNow P2Y12
      assay, Multiplate and LTA at baseline and over time (1, 3, 5, 7, 9, and 11 days)
      post-LD treatment. Recovery of platelet function was defined as occurring on the
      first day that P2Y12 reaction units were <=60 below pre-drug values and remained
      in this range. The relationship between platelet inhibition at 24 h post-LD to
      time of recovery was also evaluated. Recovery of platelet function occurred from
      days 3-7 for clopidogrel-treated subjects, by day 7 for patients treated with
      prasugrel 30 mg and from days 7-9 for patients treated with prasugrel 60 mg. Time
      for platelet function to return to baseline was independent of treatment
      assignment, reflecting instead the extent of platelet inhibition at 24 h post-LD
      (correlation coefficient = 0.81, p < 0.001), which was greater following a
      prasugrel LD. CONCLUSIONS: Prasugrel-treated subjects require a longer time for
      recovery compared with clopidogrel due to greater post-LD platelet inhibition.
      Platelet function testing after cessation of P2Y(12) receptor blockers may prove
      useful to guide the timing of surgical procedures (clinicaltrials.gov identifier:
      NCT01107899).

PMID- 22372532
TI  - Enhanced platelet-derived microparticle formation is associated with carotid
      atherosclerosis in convalescent stroke patients.
AB  - Platelets participate in the development and progression of atherosclerosis.
      During this process they interact with endothelial cells and leukocytes.
      Therefore, we investigated the associations between carotid atherosclerosis and
      platelet reactivity markers. The platelet surface expression of P-selectin
      (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding
      of PAC-1), as well as the fraction of platelet-derived microparticles (PMPs)
      prior to and after platelet stimulation with TRAP or ADP, were determined using
      flow cytometry in 94 subjects in the convalescent phase of ischaemic stroke and
      in 76 disease controls. The mean common carotid intima-media thickness (CCA(mean)
      IMT), maximal common carotid IMT (CCA(max) IMT) and maximal bifurcation IMT
      (BIF(max) IMT) were measured bilaterally using B mode, colour Doppler
      ultrasonography. In stroke subjects IMT within CCA and BIF were greater than in
      disease controls and the percentage of PMPs prior to and after ex vivo
      stimulation with agonists was significantly higher than in controls. Multiple
      regression analysis revealed that PMPs were positively and independently
      correlated with both CCA(mean) IMT (beta = 0.23; p < 0.01) and stroke (beta =
      0.21; p<0.01), while PAC-1 binding to platelets activated with ADP was negatively
      and independently associated with CCA(mean) IMT (beta = -0.29; p<0.001) and
      atherosclerotic carotid plaque presence (beta = -0.28, p = 0.003). We found a
      positive association between enhanced PMP formation and atherosclerotic
      thickening of carotid intima-media or carotid plaque in patients after ischaemic
      stroke. We demonstrated that diminished expression of active GPIIb/IIIa in the
      ADP-activated platelets is associated with increased carotid IMT, independently
      of stroke.

PMID- 22372533
TI  - Platelet activation by Streptococcus sanguinis is accompanied by MAP kinase
      phosphorylation.
AB  - There is increasing interest in the role of infections in atherothrombotic
      conditions. In particular, bacteria, notably those of oral origin, have been
      shown to activate platelets using a variety of mechanisms. Previous studies have
      shown that S. sanguinis strain 2017-78 induces platelet aggregation which
      requires the presence of both vWF and IgG. This aggregation is accompanied by the
      consecutive phosphorylation/desphosphorylation/rephosphorylation of several
      signalling proteins. The first two phases are thromboxane-dependent whereas the
      rephosphorylation phase is mediated by engagement of the alphaIIbbeta3 integrin.
      Here signalling events, specifically the potential role of MAP kinases,
      associated with S. sanguinis strain 2017-78-induced platelet activation have been
      further examined using an immunoblotting approach. The addition of S. sanguinis
      strain 2017-78 caused a similar triphasic phosphorylation profile of the platelet
      MAP kinase Erk2 to that seen with other phosphoproteins. Pretreatment with
      aspirin or RGDS did not affect 2017-78-induced Erk2 phosphorylation or
      desphosphorylation but both inhibited the rephosphorylation phase. In contrast
      the level of 2017-78-induced platelet MAP kinase p38 phosphorylation remained at
      an elevated level, and this was unaffected by aspirin. Similarly, 2017-78-induced
      cPLA(2) phosphorylation remained above basal levels during the aggregation
      process. The p38 inhibitor SB203580 inhibited S. sanguinis-induced aggregation
      with no effect on the phosphorylation of either p38 or cPLA(2). Thus the current
      study demonstrates the activation of both the Erk2 and p38 forms of MAP kinases,
      and of cPLA(2), in platelets stimulated with S. sanguinis strain 2017-78, and is
      consistent with a role for Erk2, but not for p38, in the cPLA(2) phosphorylation
      in response to S. sanguinis.

PMID- 22372534
TI  - Estrogenic effect of ginsenoside Rg1 on APP processing in post-menopausal
      platelets.
AB  - Ginsenoside Rg1, an active component of high abundance in ginseng, has recently
      been reported to possess neuroprotective properties and also identified as a
      potent phytoestrogen. However, it is unknown whether Rg1 intervenes in amyloid
      precursor protein (APP) processing, and whether such intervention is associated
      with its estrogenic activity. Using human platelets, this study demonstrated that
      Rg1 promoted alpha-secretase cleavage of APP via estrogenic activity. The mitogen
      activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK)
      pathway may be involved in the effect of Rg1 on APP metabolism as a downstream
      effector of estrogen receptor (ER) extranuclear signaling. Estrogen withdrawal is
      a risk factor for the onset of Alzheimer's disease (AD). Rg1 exerts estrogenic
      activity in APP processing in platelets supporting the use of this compound in
      the prevention of AD, in particular in postmenopausal females.

PMID- 22372535
TI  - A family with Bolzano-type Bernard-Soulier syndrome carries a benign A1939T MYH9
      mutation.

PMID- 22372536
TI  - A myocardial ischemia- and reperfusion-induced injury is mediated by reactive
      oxygen species released from blood platelets.
AB  - In recent experimental studies, blood platelets have been found to exhibit some
      cardiodepressive effects in ischemic and reperfused guinea pig hearts independent
      of thrombus formation. These effects seemed to be mediated by reactive oxygen
      species (ROS). However, the source of these ROS - platelets or heart - remained
      still unknown. Isolated, buffer-perfused and pressure-volume work performing
      guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min
      duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were
      administered as 1 min bolus (20 000 thrombocytes/ul perfusion buffer) in the 15th
      min of ischemia or in the 1st or 5th min of reperfusion in the presence of
      thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was
      expressed as ratio between postischemic and preischemic EHW in percent.
      Intracoronary platelet retention (RET) was quantified as percent of platelets
      applied. In a second set of experiments, thrombocytes were incubated with 10 uM
      of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed
      twice, thereafter, and administered according to the same protocol as described
      above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but
      without application of platelets served as controls. Controls without application
      of platelets did not reveal a severe compromisation of myocardial function (REHW
      85.5 +/- 1%). However, addition of platelets during ischemia or in the 1st or 5th
      min of reperfusion led to a significant reduction of REHW as compared with
      controls (REHW 62.4 +/- 6, 53.9 +/- 3, 40.5 +/- 3, respectively). Application of
      platelets pretreated with diphenyliodonium chloride did not reveal any
      cardiodepressive effects being significantly different from controls without
      platelet application. Moreover, treatment of platelets with diphenyliodonium
      chloride did not significantly decrease intracoronary platelet retention. In
      conclusion, these results demonstrate that cardiodepressive effects of human
      thrombocytes in ischemic and reperfused guinea pig hearts are mediated by ROS
      released from thrombocytes and not the heart.

PMID- 22372537
TI  - Insight into the redox regulation of the phosphoglucan phosphatase SEX4 involved
      in starch degradation.
AB  - Starch is the major carbohydrate reserve in plants, and is degraded for growth at
      night. Starch breakdown requires reversible glucan phosphorylation at the granule
      surface by novel dikinases and phosphatases. The dual-specificity phosphatase
      starch excess 4 (SEX4) is required for glucan desphosphorylation; however,
      regulation of the enzymatic activity of SEX4 is not well understood. We show that
      SEX4 switches between reduced (active) and oxidized (inactive) states, suggesting
      that SEX4 is redox-regulated. Although only partial reactivation of SEX4 was
      achieved using artificial reductants (e.g. dithiothreitol), use of numerous
      chloroplastic thioredoxins recovered activity completely, suggesting that
      thioredoxins could reduce SEX4 in vivo. Analysis of peptides from oxidized and
      reduced SEX4 identified a disulfide linkage between the catalytic cysteine at
      position 198 (Cys198) and the cysteine at position 130 (Cys130) within the
      phosphatase domain. The position of these cysteines was structurally analogous to
      that for known redox-regulated dual-specificity phosphatases, suggesting a common
      mechanism of reversible oxidation amongst these phosphatases. Mutation of Cys130
      renders SEX4 more sensitive to oxidative inactivation and less responsive to
      reductive reactivation. Together, these results provide the first biochemical
      evidence for a redox-dependent structural switch that regulates SEX4 activity,
      which represents the first plant phosphatase known to undergo reversible
      oxidation via disulfide bond formation like its mammalian counterparts.

PMID- 22372538
TI  - Chemoenzymatic synthesis of O-mannosylpeptides in solution and on solid phase.
AB  - O-mannosyl glycans are known to play an important role in regulating the function
      of alpha-dystroglycan (alpha-DG), as defective glycosylation is associated with
      various phenotypes of congenital muscular dystrophy. Despite the well-established
      biological significance of these glycans, questions regarding their precise
      molecular function remain unanswered. Further biological investigation will
      require synthetic methods for the generation of pure samples of homogeneous
      glycopeptides with diverse sequences. Here we describe the first total syntheses
      of glycopeptides containing the tetrasaccharide NeuNAcalpha2-3Galbeta1
      4GlcNAcbeta1-2Manalpha, which is reported to be the most abundant O-mannosyl
      glycan on alpha-DG. Our approach is based on biomimetic stepwise assembly from
      the reducing end and also gives access to the naturally occurring mono-, di-, and
      trisaccharide substructures. In addition to the total synthesis, we have
      developed a "one-pot" enzymatic cascade leading to the rapid synthesis of the
      target tetrasaccharide. Finally, solid-phase synthesis of the desired
      glycopeptides directly on a gold microarray platform is described.

PMID- 22372539
TI  - First report of idiopathic segmental ureteritis successfully treated by steroid
      therapy.
AB  - We report a case of bilateral idiopathic segmental ureteritis in a 52-year-old
      woman. The diagnosis was established by imaging studies (magnetic resonance
      imaging/computed tomography scan), ureteroscopy and biopsies. The left side
      improved spontaneously, but the right ureteral stricture persisted after 3 months
      of ureteral stenting. Administration of prednisolone effectively relieved
      obstruction on the right side after 4 months. This is the first report of
      idiopathic segmental ureteritis successfully treated by steroid therapy, without
      invasive open procedures.

PMID- 22372540
TI  - Diagnosis and treatment of community-acquired pneumonia in children.

PMID- 22372541
TI  - Macroscopic and microscopic analysis of knife stab wounds on fleshed and clothed
      ribs.
AB  - Stab wounds upon bone are analyzed to interpret the weapon used and the physical
      context in which the attack occurred. The literature demonstrates that most
      research conducted pertaining to wound patterns has been carried out on defleshed
      and unclothed bone samples, not adequately replicating actual circumstances. For
      this research, six half pig torsos (Sus scrofa), fleshed (including muscle, fat,
      epidermis, and dermis layers) and clothed, were stabbed using three knife types,
      applying both straight and downward thrusts. Analysis conducted macroscopically
      and through a scanning electron microscope with an environmental secondary
      electron detector revealed a general lack of consistency in wound pattern and
      associated secondary effects. Consequently, it was not possible to establish
      wound pattern per knife type as suggested in previous research or relate it to
      stab motion. Advantage of microscopic analysis was evident in recognizing wound
      traits and observation of trace evidence not visible macroscopically.

PMID- 22372542
TI  - Leishmania major peroxidase is a cytochrome c peroxidase.
AB  - Leishmania major peroxidase (LmP) exhibits both ascorbate and cytochrome c
      peroxidase activities. Our previous results illustrated that LmP has a much
      higher activity against horse heart cytochrome c than ascorbate, suggesting that
      cytochrome c may be the biologically important substrate. To elucidate the
      biological function of LmP, we have recombinantly expressed, purified, and
      determined the 2.08 A crystal structure of L. major cytochrome c (LmCytc). Like
      other types of cytochrome c, LmCytc has an electropositive surface surrounding
      the exposed heme edge that serves as the site of docking with redox partners.
      Kinetic assays performed with LmCytc and LmP show that LmCytc is a much better
      substrate for LmP than horse heart cytochrome c. Furthermore, unlike the well
      studied yeast system, the reaction follows classic Michaelis-Menten kinetics and
      is sensitive to an increasing ionic strength. Using the yeast cocrystal as a
      control, protein-protein docking was performed using Rosetta to develop a model
      for the binding of LmP and LmCytc. These results suggest that the biological
      function of LmP is to act as a cytochrome c peroxidase.

PMID- 22372543
TI  - Combined superficial & deep fractional skin treatment for photodamaged skin--a
      prospective clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Deep microthermal zones targeted by Fractional CO(2)
      lasers stimulate fibroblast activity, whereas superficial microthermal zones
      target the epidermal layer pigment. The new combination modality enables
      targeting both deep and superficial disorders. The study is designed to evaluate
      the improvement in photodamage and determine downtime. MATERIALS AND METHODS:
      This IRB approved study was aimed to evaluate histology phenotype of combined
      deep and superficial skin resurfacing. A 120-micron, focused CO(2) laser beam was
      used to create both deep and superficial fractional skin resurfacing using
      ultrapulse and continuous wave laser modes, respectively. Fifteen patients (skin
      types II-V) underwent combined treatment and returned for assessment at 1 week, 1
      and 3 months to evaluate the clinical outcome. Additional histological analysis
      of human tissue was performed to elucidate the combined impact on tissue.
      RESULTS: Pre-clinical histologies demonstrated the ability to achieve fractional
      discrete 1.3-mm-diameter spots of superficial ablation with a uniform shallow and
      narrow area of coagulation while maintaining the deep, fractional 120-micron
      ablation spot capabilities. Histologies of the human tissue confirmed the ability
      to control both superficial and deep fractional treatment using a single
      handpiece. Pigmentation was greatly reduced at the 1 month follow-up with
      significant textural improvement. No unexpected AEs or SAEs were reported.
      CONCLUSION: The new modality enables combined superficial and deep fractional
      impact and improvements that are demonstrated at both the phenotype and tissue
      level.

PMID- 22372544
TI  - Therapy innovation for the treatment of pancreatic neuroendocrine tumors.
AB  - INTRODUCTION: Traditional therapeutic approaches for patients with advanced
      neuroendocrine tumors (NETs) have included treatment with somatostatin analogs,
      hepatic-directed therapies, interferon and cytotoxic chemotherapy. Current
      knowledge about biological behavior of pancreatic neuroendocrine tumors (pNETs)
      has increased in the last decade, and some studies have been conducted to
      translate in the clinical setting. Among several molecular agents investigated in
      patients with progressive pNETs, everolimus and sunitinib have been studied in
      large Phase III trials. Both have produced significant benefit, with improvement
      in progression-free survival. These results were published last year by NEJM and
      were updated at the ASCO Annual Meeting in June 2011. AREAS COVERED: This review
      focuses on the potential molecular targets in pancreatic NETs in the light of
      recent advances. Furthermore, it summarizes the available data for targeted
      agents from Phase II and III trials open to patients with this tumor. EXPERT
      OPINION: These new agents are likely to play an increasingly important role in
      the future management of advanced pNETs. Their use in earlier phases of the
      disease could improve clinical outcome, avoiding side effects of the more toxic
      chemotherapy. The challenge in medical treatment of pNET is to define the
      patients who can benefit from this innovative therapy; future research should be
      directed to find predictive markers for response to the targeted agent.

PMID- 22372545
TI  - Angiogenin up-regulation correlates with adverse clinicopathological and
      biological factors, increased microvascular density and poor patient outcome in
      neuroblastomas.
AB  - AIMS: As new biomarkers are urgently needed to identify children with high-risk
      neuroblastoma (NB), we studied the contribution of angiogenin (ANG) to
      angiogenesis and its association with clinicopathological and biological features
      and patient outcome in NB. METHODS AND RESULTS: Ninety NBs and 12 ganglioneuromas
      (GNs) were immunostained for ANG and CD31. ANG expression in NB tumoral cells
      (ANG scores) and vessels [ANG microvascular density (MVD)] and total MVD (CD31
      MVD) were determined. The ANG score was significantly greater in NBs than in GNs
      (P = 0.015) and in NBs from children with stage 4 tumours, high-risk disease,
      unfavourable pathology (P < 0.001 for each), MYCN amplification (P = 0.003), and
      1p deletion (P = 0.002). ANG scores correlated with ANG MVD and CD31 MVD (P <
      0.001 for each). Total ANG and CD31 protein levels, measured with a sensitive
      enzyme-linked immunosorbent assay, were highly correlated (P = 0.003). High ANG
      scores were associated with decreased overall and event-free survival (log-rank
      test, P = 0.025 and P = 0.018, respectively). High ANG MVD was associated with
      decreased overall and event-free survival (log-rank test, P = 0.009 and P =
      0.026, respectively). High CD31 MVD was associated with decreased event-free
      survival (P = 0.045). CONCLUSIONS: The strong correlation of ANG up-regulation
      with total MVD and adverse clinicopathological and biological factors indicates
      that ANG supports growth and progression in NB.

PMID- 22372547
TI  - Slower rate of compensatory hypertrophy in pediatric en bloc kidney
      transplantation in a pediatric recipient.

PMID- 22372546
TI  - Long-distance gene flow and adaptation of forest trees to rapid climate change.
AB  - Forest trees are the dominant species in many parts of the world and predicting
      how they might respond to climate change is a vital global concern. Trees are
      capable of long-distance gene flow, which can promote adaptive evolution in novel
      environments by increasing genetic variation for fitness. It is unclear, however,
      if this can compensate for maladaptive effects of gene flow and for the long
      generation times of trees. We critically review data on the extent of long
      distance gene flow and summarise theory that allows us to predict evolutionary
      responses of trees to climate change. Estimates of long-distance gene flow based
      both on direct observations and on genetic methods provide evidence that genes
      can move over spatial scales larger than habitat shifts predicted under climate
      change within one generation. Both theoretical and empirical data suggest that
      the positive effects of gene flow on adaptation may dominate in many instances.
      The balance of positive to negative consequences of gene flow may, however,
      differ for leading edge, core and rear sections of forest distributions. We
      propose future experimental and theoretical research that would better integrate
      dispersal biology with evolutionary quantitative genetics and improve predictions
      of tree responses to climate change.

PMID- 22372548
TI  - Assessment of generalizability, applicability and predictability (GAP) for
      evaluating external validity in studies of universal family-based prevention of
      alcohol misuse in young people: systematic methodological review of randomized
      controlled trials.
AB  - AIMS: To assess external validity characteristics of studies from two Cochrane
      Systematic Reviews of the effectiveness of universal family-based prevention of
      alcohol misuse in young people. METHODS: Two reviewers used an a priori developed
      external validity rating form and independently assessed three external validity
      dimensions of generalizability, applicability and predictability (GAP) in
      randomized controlled trials. RESULTS: The majority (69%) of the included 29
      studies were rated 'unclear' on the reporting of sufficient information for
      judging generalizability from sample to study population. Ten studies (35%) were
      rated 'unclear' on the reporting of sufficient information for judging
      applicability to other populations and settings. No study provided an assessment
      of the validity of the trial end-point measures for subsequent mortality,
      morbidity, quality of life or other economic or social outcomes. Similarly, no
      study reported on the validity of surrogate measures using established criteria
      for assessing surrogate end-points. CONCLUSIONS: Studies evaluating the benefits
      of family-based prevention of alcohol misuse in young people are generally
      inadequate at reporting information relevant to generalizability of the findings
      or implications for health or social outcomes. Researchers, study authors, peer
      reviewers, journal editors and scientific societies should take steps to improve
      the reporting of information relevant to external validity in prevention trials.

PMID- 22372549
TI  - Evaluation of overnight storage conditions for autologous peripheral blood stem
      cell products: comparison of three different conditions.
AB  - BACKGROUND: Overnight (ON) storage of peripheral blood stem cell (PBSC) occurs
      frequently in clinical settings. However, there are no standard guidelines for
      optimal storage conditions of freshly harvested PBSC. The aim of this study was
      to investigate the influence of storage temperatures on the quality of autologous
      PBSC and establish optimal storage conditions before cryopreservation. METHODS: A
      retrospective analysis was performed on 260 PBSC harvests according to pre
      cryopreservation conditions: immediate processing or ON storage at room
      temperature (RT). For direct comparison, 30 autologous PBSC products were
      collected prospectively and prepared under three different pre-cryopreservation
      conditions: immediate processing, ON storage at 4 degrees C and ON storage at RT.
      The recovery of CD34(+) cells, post-thaw CFU-GM count and viability were
      analysed. RESULTS: Retrospective analysis revealed that post-thaw CFU-GM count
      was significantly lower when PBSC were stored ON at RT compared to when
      immediately processed (136.4 vs. 409.6/MUl). Prospective analysis showed a mean
      recovery of CD34(+) cells of 65.5 +/- 25.1%, 70.5 +/- 27.4% and 35.9 +/- 25.1%
      for immediate processing, ON storage at 4 degrees C and ON storage at RT,
      respectively. Similarly, mean viability and CFU-GM counts were significantly
      reduced when stored ON at RT compared to when immediately processed or stored ON
      at 4 degrees C (60.4 +/- 25.6 vs. 84.1 +/- 12.9 vs. 82.7 +/- 12.6%, 15.7 +/- 25.7
      vs. 398.5 +/- 906.2 vs. 350.0 +/- 847.9/MUl, respectively). CONCLUSIONS: ON
      storage of autologous PBSC at RT significantly decreased the quality of HPCs.
      These data indicate that ON storage of autologous PBSC at 4 degrees C would be
      the most reasonable approach for maintaining the quality of HPCs when immediate
      processing is not possible.

PMID- 22372550
TI  - Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent
      CDK/JAK2/FLT3 inhibitor.
AB  - SB1317 (TG02) is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. To
      evaluate full potential of this development candidate, we conducted drug
      metabolism and pharmacokinetic studies of this novel anti-cancer agent. SB1317
      was soluble, highly permeable in Caco-2 cells, and showed > 99% binding to plasma
      from mice, dog and humans. It was metabolically stable in human and dog liver
      microsomes relative to mouse and rat. SB1317 was mainly metabolized by CYP3A4 and
      CY1A2 in vitro. SB1317 did not inhibit any of the major human CYPs in vitro
      except CYP2D6 (IC50=1 MUM). SB1317 did not significantly induce CYP1A and CYP3A4
      in human hepatocytes in vitro. The metabolic profiles in liver microsomes from
      preclinical species were qualitatively similar to humans. In pharmacokinetic
      studies SB1317 showed moderate to high systemic clearance (relative to liver
      blood flow), high volume of distribution ( > 0.6 L/kg), oral bioavailability of
      24%, ~ 4 and 37% in mice, rats and dogs, respectively; and extensive tissue
      distribution in mice. The favorable ADME of SB1317 supported its preclinical
      development as an oral drug candidate.

PMID- 22372551
TI  - Molecular analysis and modeling of inactivation of human CYP2D6 by four mechanism
      based inactivators.
AB  - Human cytochrome P450 2D6 (CYP2D6) is involved in metabolism of approximately 25%
      of pharmaceutical drugs. Inactivation of CYP2D6 can lead to adverse drug
      interactions. Four inactivators of CYP2D6 have previously been identified: 5
      Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1
      piperazinyl]pyrimidine(SCH66712), (1-[(2-ethyl- 4-methyl-1H-imidazol-5-yl)
      methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine(EMTPP), paroxetine, and 3,4
      methylenedioxymethamphetamine (MDMA). All four contain planar, aromatic groups
      as well as basic nitrogens common to CYP2D6 substrates. SCH66712 and EMTPP also
      contain piperazine groups and substituted imidazole rings that are common in
      pharmaceutical agents, though neither of these compounds is clinically relevant.
      Paroxetine and MDMA contain methylenedioxyphenyls. SCH66712 and EMTPP are both
      known protein adductors while paroxetine and MDMA are probable heme modifiers.
      The current study shows that each inactivator displays Type I binding with Ks
      values that vary by 2-orders of magnitude with lower Ks values associated with
      greater inactivation. Comparison of KI, kinact, and partition ratio values shows
      SCH66712 is the most potent inactivator. Molecular modeling experiments using
      AutoDock identify Phe120 as a key interaction for all four inactivators with face
      to-face and edge-to-face pi interactions apparent. Distance between the ligand
      and heme iron correlates with potency of inhibition. Ligand conformations were
      scored according to their binding energies as calculated by AutoDock and
      correlation was observed between molecular models and Ks values.

PMID- 22372552
TI  - Comparative analysis of in vitro rat liver metabolism of the antimalarial
      primaquine and a derived imidazoquine.
AB  - The present study provides proof-of-concept regarding the expectedly high
      enzymatic stability of primaquinederived imidazolidin-4-ones, imidazoquines,
      formerly developed as alternatives to the parent antimalarial with potentially
      improved oral bioavailability [J. Med. Chem., 2009, 52, 7800-7807]. This study
      provides relevant experimental evidence on the remarkably low propensity of
      imidazoquines to undergo metabolic conversions mediated by rat liver enzymes.
      This, together with favourable key ADME parameters previously predicted for these
      compounds [Bioorg. Med. Chem. Lett. 2009, 19, 6914-6917], and proven lack of
      acute toxicity in mice, further reinforces the role of imidazoquines as reference
      leads for the development of novel primaquine surrogates. This is a particularly
      relevant issue in the present status of malaria chemotherapy worldwide, where
      primaquine remains the sole drug in clinical use able to block transmission
      between infected persons and the insect vector and to effectively act on liver
      stage parasite forms, including hypnozoites.

PMID- 22372553
TI  - Changes of drug metabolizing enzymes in the liver of male sheep exposed to either
      cypermethrin or dimethoate.
AB  - Xenobiotics such as insecticides are metabolized to more or less toxic
      metabolites by drug-metabolizing enzymes including cytochrome P450 (Cyp P450),
      cytochrome b5 (Cyp b5), NADPH-cytochrome c reductase (Cyt.c R), N
      nitrosdimethylamine-N-demethylase I (NDMA-dI), glutathione (GSH), glutathione s
      transferase (GST), and glutathione reductase (GR). Therefore, the present study
      showed the influence of oral administration of cypermethrin (6 and 12 mg/kg/day)
      and dimethoate (1.6 and 3.2 mg/kg/day) for 63 consecutive days on the activities
      of the above mentioned enzymes in the livers of male sheep. Low and high
      treatments of sheep with cypermethrin significantly increased the levels of Cyp
      P450 by 56% and 98%, Cyp b5 by 65% and 80%, GSH by 68% and 74%, and Cyt.c R by
      67% and 98%, respectively in a dose-dependent manner. However, low dose of
      cypermethrin increased the activities of GST and GR by 56% and 91% respectively.
      In addition, low and high dose-treatments with dimethoate increased the hepatic
      contents of Cyp P450 by 27% and 40%, GSH by 259% and 132%, whereas NDMA-dI
      decreased by 27 and 55% respectively, and no change in the content of Cyp b5 and
      the activity of Cyt.c-R at any given dose of this compound. It is concluded that
      exposure to cypermethrin and dimethoate significantly changed the hepatic
      activity of phases I & II drugmetabolizing enzymes in sheep, and these changes
      are mainly dependent on the administred dose, and also on the type of the tested
      insecticides. Also, such changes should be considered when therapeutic drugs
      administered to people exposed to such insecticides.

PMID- 22372554
TI  - Evaluation of time-dependent cytochrome p450 inhibition in a high-throughput,
      automated assay: introducing a novel area under the curve shift approach.
AB  - Early in the drug discovery process, the identification of cytochrome P450 (CYP)
      time-dependent inhibition (TDI) is an important step for compound optimization.
      Here we describe a high-throughput, automated method for the evaluation of TDI
      utilizing human liver microsomes and conventional CYP-specific mass spectrometer
      based probes in a 384-well format. One of the key differences from other
      published TDI assays is the use of a shift in area the under curve of the percent
      activity remaining versus inhibitor concentration plot (AUC shift) rather than
      the traditional fold-shift in IC50, to determine the magnitude of TDI. An AUC
      shift of < 15% suggests negative TDI and > 15% suggests potential TDI. This AUC
      shift was used to achieve quantitative data reporting, even in the case of weak
      inhibitors for which IC50 values cannot be quantified. An Agilent Technologies
      BioCel 1200 System was programmed such that the TDI liability of up to 77 test
      compounds, incubated at four test concentrations, with and without NADPH in the
      pre-incubation, can be analyzed in a single run. The detailed automated
      methodology, assay validation, data reporting and the novel TDI AUC shift
      approach to describe magnitude of TDI are presented.

PMID- 22372555
TI  - Relevance of the salvage pathway to N-hexanoylsphingosine metabolic
      downregulation in human neurotumor cells: implications for apoptosis.
AB  - N-Hexanoylsphingosine (C6-Cer) is currently being evaluated as an antineoplastic
      agent, after preclinical studies showing its property to reduce tumor growth.
      Herein it is reported that the cytotoxic effect of C6-Cer, as observed in CHP-100
      neurotumor cells, impinges on its continuous uptake from the culture medium,
      ensuring maintainance of elevated steady-state intracellular levels, in the face
      of the rapid metabolic removal. C6-Cer metabolism not only does occur by direct
      glucosylation but is also relevantly driven by utilization via the sphingosine
      salvage pathway, leading to accumulation of natural ceramide that, in CHP-100
      cells, has been demonstrated to lack apoptotic properties. Upon inhibition of
      glucosylceramide synthase by D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1
      propanol, previously shown to enhance C6-Cer cytotoxic activity, short-chain
      ceramide metabolism was partly redirected to the salvage pathway, likely
      attenuating the chemosensitizing effect of the above-mentioned compound.
      Elucidation of the metabolic machinery driving C6-Cer recycling via the salvage
      pathway might thus be relevant for optimization of its therapeutic utilization.

PMID- 22372556
TI  - Ground-state and excited-state structures of tungsten-benzylidyne complexes.
AB  - The molecular structure of the tungsten-benzylidyne complex trans
      W(=CPh)(dppe)(2)Cl (1; dppe = 1,2-bis(diphenylphosphino)ethane) in the singlet
      (d(xy))(2) ground state and luminescent triplet (d(xy))(1)(pi*(WCPh))(1) excited
      state (1*) has been studied using X-ray transient absorption spectroscopy, X-ray
      crystallography, and density functional theory (DFT) calculations. Molecular
      orbital considerations suggest that the W-C and W-P bond lengths should increase
      in the excited state because of the reduction of the formal W-C bond order and
      decrease in W->P pi-backbonding, respectively, between 1 and 1*. This latter
      conclusion is supported by comparisons among the W-P bond lengths obtained from
      the X-ray crystal structures of 1, (d(xy))(1)-configured 1(+), and (d(xy))(2)
      [W(CPh)(dppe)(2)(NCMe)](+) (2(+)). X-ray transient absorption spectroscopic
      measurements of the excited-state structure of 1* reveal that the W-C bond length
      is the same (within experimental error) as that determined by X-ray
      crystallography for the ground state 1, while the average W-P/W-Cl distance
      increases by 0.04 A in the excited state. The small excited-state elongation of
      the W-C bond relative to the M-E distortions found for M(=E)L(n) (E = O, N)
      compounds with analogous (d(xy))(1)(pi*(ME))(1) excited states is due to the pi
      conjugation within the WCPh unit, which lessens the local W-C pi-antibonding
      character of the pi*(WCPh) lowest unoccupied molecular orbital (LUMO). These
      conclusions are supported by DFT calculations on 1 and 1*. The similar core bond
      distances of 1, 1(+), and 1* indicates that the inner-sphere reorganization
      energy associated with ground- and excited-state electron-transfer reactions is
      small.

PMID- 22372557
TI  - In vitro 2-deoxy-2-[18F]fluoro-D-glucose uptake: practical considerations.
AB  - In oncology 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]-FDG), a glucose analogue,
      is the most used positron emission tomography (PET) tracer. There are however
      some limitations due to low metabolic activity or high surrounding physiological
      uptake in several tumors or regions. Investigating new tracers or methods is
      expensive and elaborative when animal experiments or phase I clinical trials are
      used. In vitro experiments can overcome these limitations. We analyzed the
      influence of incubation time, cell medium conditions, administered activity, and
      cell density on [(18)F]-FDG uptake in six different cell cultures. Glucose
      transporter 1 (GLUT1)- and hexokinase 2 (HK2)-expression at high and low cell
      density was analyzed using immunocytochemistry. FDG-uptake increases over time
      and absence of glucose in the incubation medium increases uptake. By increasing
      the administered activity, uptake per protein also increases and tracer uptake
      per protein is lower at higher cell densities. Immunocytochemical analysis
      reveals a lower expression of both GLUT1 and HK2 at higher cell concentrations.
      All investigated parameters influenced FDG uptake and therefore we can conclude
      it is of utmost importance to keep administered activity, incubation medium, and
      time constant and to correct uptake when cell density changes due to
      environmental conditions, such as therapy.

PMID- 22372558
TI  - Specific antitumor immunity induced by cross-linking complex heat shock protein
      72 and alpha-fetoprotein.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies over the
      world. Alpha-fetoprotein (AFP) is an oncofetal protein during HCC development
      that could generate weaker and less reproducible antitumor protection, and it may
      serve as a target for immunotherapy. Therefore, it is imperative to enhance its
      immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing
      tumors. In this study, by way of glutaraldehyde cross-linking, we constructed a
      potential therapeutic protein complex vaccine, heat shock protein 72 (HSP72)/AFP.
      Our results demonstrated that AFP and HSP72 synergistically exhibited significant
      increases in AFP-specific CD8(+) T cell responses and impressive antitumor
      effects against AFP-expressing tumors. Priming mice with the reconstructed
      vaccine, we elicited robust strong protective immunity. Our study suggests that a
      tumor vaccine by cross-linking tumor antigen and HSP72 is a promising approach
      for cancer therapy.

PMID- 22372559
TI  - Nonlinear correlation spectroscopy (NLCS).
AB  - We present a novel concept for optical spectroscopy called nonlinear correlation
      spectroscopy (NLCS). NLCS analyses coherent field fluctuations of the second and
      third harmonic light generated by diffusing nanoparticles. Particles based on
      noncentrosymmetric nonlinear materials such as KNbO(3) show a strong second as
      well as third harmonic response. The method and the theory are introduced and
      experimental NLCS results in fetal calf serum are presented showing the promising
      selectivity of this technique for measurement in complex biological environments.

PMID- 22372560
TI  - Fourth-line rescue therapy with rifabutin in patients with three Helicobacter
      pylori eradication failures.
AB  - BACKGROUND: In some cases, Helicobacter pylori infection persists even after
      three eradication treatments. AIM: To evaluate the efficacy of an empirical
      fourth-line rescue regimen with rifabutin in patients with three eradication
      failures. METHODS:  DESIGN: Multicentre, prospective study. PATIENTS: In whom the
      following three treatments had consecutively failed: first (PPI + clarithromycin
      + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI
      + amoxicillin + levofloxacin). INTERVENTION: A fourth regimen with rifabutin (150
      mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed
      for 10 days. OUTCOME: Eradication was confirmed by (13) C-urea breath test 4-8
      weeks after therapy. Compliance and tolerance: Compliance was determined through
      questioning and recovery of empty medication envelopes. Adverse effects were
      evaluated using a questionnaire. RESULTS: One-hundred patients (mean age 50
      years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight
      patients did not take the medication correctly (in six cases due to adverse
      effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI
      = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients:
      nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7),
      diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia
      (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150,000 platelets) (2),
      headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in
      all cases. CONCLUSIONS: Even after three previous H. pylori eradication failures,
      an empirical fourth-line rescue treatment with rifabutin may be effective in
      approximately 50% of the cases. Therefore, rifabutin-based rescue therapy
      constitutes a valid strategy after multiple previous eradication failures with
      key antibiotics, such as clarithromycin, metronidazole, tetracycline and
      levofloxacin.

PMID- 22372562
TI  - Comprehensive review of the clinical application of autologous mesenchymal stem
      cells in the treatment of chronic wounds and diabetic bone healing.
AB  - Chronic ulcerations are a physical and financial burden to the health and
      economic establishment in the United States and Worldwide. Improvements in
      biotechnology and knowledge in stem cell applications have progressed and basic
      science results are making their way slowly into the clinical arena. Chronic
      wounds and diabetic bone healing are the key components in the limb salvage of
      the common diabetic foot. We have examined the current available literature and
      present the latest on stem cells applications as a novel clinical technique in
      the treatment of chronic wound and diabetic bone healing and their impact in the
      treatment paradigm of patients.

PMID- 22372561
TI  - Cell-to-cell communication and vascular dementia.
AB  - OBJECTIVE: VaD is the second-most common form of dementia, second only to that
      caused by AD. As the name indicates, VaD is predominantly considered a disease
      caused by vascular phenomena. METHODS: In this invited review, we introduce the
      reader to recent developments in defining VaD as a unique form of dementia by
      reviewing the current pertinent literature. We discuss the clinical and
      experimental evidence that supports the notion that the microcirculation,
      specifically cell-to-cell communication, likely contributes to the development of
      VaD. Through exploration of the concept of the NVU, we elucidate the extensive
      cerebrovascular communication that exists and highlight models that may help test
      the contribution(s) of cell-to-cell communication at the microvascular level to
      the development and progression of VaD. Lastly, we explore the possibility that
      some dementia, generally considered to be purely neurodegenerative, may actually
      have a vascular component at the neurovascular level. CONCLUSION: This latter
      recognition potentially broadens the critical involvement of microvascular events
      that contribute to the numerous dementias affecting an increasingly larger sector
      of the adult population.

PMID- 22372563
TI  - Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and
      refolds by parallel pathways via cooperative or sequential events.
AB  - The discovery of G-quadruplexes and other DNA secondary elements has increased
      the structural diversity of DNA well beyond the ubiquitous double helix. However,
      it remains to be determined whether tertiary interactions can take place in a DNA
      complex that contains more than one secondary structure. Using a new data
      analysis strategy that exploits the hysteresis region between the mechanical
      unfolding and refolding traces obtained by a laser-tweezers instrument, we now
      provide the first convincing kinetic and thermodynamic evidence that a higher
      order interaction takes place between a hairpin and a G-quadruplex in a single
      stranded DNA fragment that is found in the promoter region of human telomerase.
      During the hierarchical unfolding or refolding of the DNA complex, a 15
      nucleotide hairpin serves as a common species among three intermediates.
      Moreover, either a mutant that prevents this hairpin formation or the addition of
      a DNA fragment complementary to the hairpin destroys the cooperative kinetic
      events by removing the tertiary interaction mediated by the hairpin. The
      coexistence of the sequential and the cooperative refolding events provides
      direct evidence for a unifying kinetic partition mechanism previously observed
      only in large proteins and complex RNA structures. Not only does this result
      rationalize the current controversial observations for the long-range interaction
      in complex single-stranded DNA structures, but also this unexpected complexity in
      a promoter element provides additional justification for the biological function
      of these structures in cells.

PMID- 22372564
TI  - Tramadol inhibits the contractility of isolated caprine detrusor muscle.
AB  - The atypical opioid analgesic tramadol has been shown to provide beneficial
      clinical and urodynamic effects in patients with detrusor overactivity. The
      effect of tramadol on isolated detrusor muscle has not been studied. This study
      investigated the ability of tramadol to inhibit acetylcholine (ACh)-induced
      contractility of the isolated caprine (goat) detrusor muscle. The effect of three
      concentrations (30, 100 and 300 MUm) of tramadol on 10 caprine detrusor strips
      contracted by the addition of 100, 200 or 400 MUm ACh was studied. The
      sensitivity of tramadol-induced inhibition of ACh responses to treatment with the
      beta-adrenoceptor antagonist propranolol (1 MUm) and the opioid receptor
      antagonist naloxone (100 MUm) was also studied. Tramadol caused a concentration
      dependent inhibition of ACh-induced detrusor contraction that was reversed by
      raising the concentration of ACh. Propranolol, but not naloxone, reversed the
      tramadol-induced inhibition of contractions to ACh in the detrusor. These results
      suggest that tramadol inhibits ACh-induced contractility of the isolated
      detrusor. They also suggest that tramadol does so by an indirect anticholinergic
      mechanism involving the stimulation of beta-adrenoceptors. Tramadol may be useful
      in managing clinical conditions requiring relaxation of the detrusor muscle.
      Although the concentrations of tramadol needed to relax the detrusor were
      relatively high, these could be clinically attained via intravesical
      administration.

PMID- 22372565
TI  - Fatal paradoxical air embolism diagnosed by postmortem imaging and autopsy.
AB  - The recognition and visualization of an arterial gas embolism are difficult. We
      report a case of sudden death caused by paradoxical air embolism of coronary and
      cerebral arteries, diagnosed by the pre autopsy computed tomography (CT)
      scanning. A 54-year-old woman suddenly died after the self-removal of the jugular
      vein catheter. Postmortem imaging examination using CT scanning showed multiple
      gas embolisms in the cerebral arteries, pulmonary artery, right atrium and
      ventricle, left ventricle, aorta, and coronary arteries. These findings suggested
      that the occurrence of acute ischemia of the brain and heart caused by massive
      air inflow to the artery. Conventional autopsy revealed a patent foramen ovale of
      the heart. These results indicated that the patient died of paradoxical air
      embolization of the coronary and cerebral arteries through a patent foramen ovale
      because of right-to-left shunting. The use of postmortem imaging as an aid for
      conventional autopsy has proved to be of advantage in the case of gas embolism.

PMID- 22372566
TI  - Cognitive load hypothesis of item-method directed forgetting.
AB  - This study examined the effect of the processing demands of to-be-remembered
      (TBR) words on item-method directed forgetting. Experiment 1 found that a
      standard memory group remembered fewer to-be-forgotten (TBF) words than a naming
      group, in which participants simply named the TBR words during the study phase,
      even though both groups were equally instructed to forget the TBF words.
      Experiment 2 manipulated the number of TBR words in the study list, keeping the
      number of TBF words constant, and found that TBF word forgetting was more
      difficult in the few TBR words condition than the more TBR words condition. The
      same pattern was found in the result of Experiment 3 when a cued recall test,
      instead of a free recall test, was used. In all the experiments, participants
      were asked to recall the TBF words before the TBR words. These findings are
      consistent with the cognitive load hypothesis that it is easier to forget when
      there are fewer cognitive resources available during encoding.

PMID- 22372567
TI  - Comparison of accelerated methods for the extraction of phenolic compounds from
      different vine-shoot cultivars.
AB  - Most research on the extraction of high-priced compounds from vineyard/wine
      byproducts has traditionally been focused on grape seeds and skins as raw
      materials. Vine-shoots can represent an additional source to those materials, the
      characteristics of which could depend on the cultivar. A comparative study of
      hydroalcoholic extracts from 18 different vineyard cultivars obtained by
      superheated liquid extraction (SHLE), microwave-assisted extraction (MAE), and
      ultrasound-assisted extraction (USAE) is here presented. The optimal working
      conditions for each type of extraction have been investigated by using
      multivariate experimental designs to maximize the yield of total phenolic
      compounds, measured by the Folin-Ciocalteu method, and control
      hydroxymethylfurfural because of the organoleptic properties of furanic
      derivatives and toxicity at given levels. The best values found for the
      influential variables on each extraction method were 80% (v/v) aqueous ethanol at
      pH 3, 180  degrees C, and 60 min for SHLE; 140 W and 5 min microwave irradiation
      for MAE; and 280 W, 50% duty cycle, and 7.5 min extraction for USAE. SHLE
      reported better extraction efficiencies as compared to the other two approaches,
      supporting the utility of SHLE for scaling-up the process. The extracts were
      dried in a rotary evaporator, reconstituted in 5 mL of methanol, and finally
      subjected to liquid-liquid extraction with n-hexane to remove nonpolar compounds
      that could complicate chromatographic separation. The methanolic fractions were
      analyzed by both LC-DAD and LC-TOF/MS, and the differences in composition
      according to the extraction conditions were studied. Compounds usually present in
      commercial wood extracts (mainly benzoic and hydroxycinnamic acids and aldehydes)
      were detected in vine-shoot extracts.

PMID- 22372568
TI  - 980-nm laser lipolysis (LAL): About 674 procedures in 359 patients.
AB  - BACKGROUND: Since the first studies by Apfelberg in 1994, laser lipolysis (LAL)
      has been on the rise. Laser lipolysis leads to reduced operator fatigue,
      excellent patient tolerance, quick recovery time, as well as the additional
      benefit of dermal tightening. This article reports a 5-year experience of LAL and
      underlines the potential evolutions of the technique. METHODS: Between January
      2006 and December 2010, 674 LAL procedures in 359 patients were performed at the
      Antoni De Gimbernat Foundation in collaboration with the French National
      Institute of Health and Medical Research (INSERM) U703. LAL was performed with a
      980-nm diode laser after tumescent anaesthesia. The following laser settings were
      used: 600-MUm optical fiber, continuous mode, power depending on individual body
      areas (18-40 W). The cumulative energy used for each area was recorded. Early and
      late complications were defined and reviewed for the whole series. Satisfaction
      was assessed by the patients using a visual analogue scale from 0 (unsatisfied)
      to 10 (highly satisfied). RESULTS: Mean cumulative energy ranged from 12 to 60
      kJ. Ecchymoses were observed in all patients but resolved in less than 10 days. A
      touch up was needed in four patients to remove small cushions of fat missed. Mean
      patient satisfaction ranged from 6/10 to 9.5/10 depending on the treated area.
      Moreover, all patients reported they would be willing to undergo the procedure
      again, if needed. CONCLUSION: 980-nm LAL appears to be a safe, effective and
      reproducible alternative to conventional lipoplasty. However, refinements in
      dosimetry should be developed in order to optimise outcomes.

PMID- 22372569
TI  - Response to population screening for prostate cancer: an overview of available
      studies and meta-analysis.

PMID- 22372571
TI  - Solubility of CO2, H2S, and their mixture in the ionic liquid 1-octyl-3
      methylimidazolium bis(trifluoromethyl)sulfonylimide.
AB  - Gaseous solubilities of carbon dioxide (1), hydrogen sulfide (2), and their
      binary mixture (x(2) ~ 0.2, 0.5, 0.8) have been measured in the ionic liquid 1
      octyl-3-methylimidazolium bis(trifluoromethyl)sulfonylimide ([C(8)mim][Tf(2)N])
      at temperatures ranging from (303.15 to 353.15) K and at pressures under 2 MPa.
      The observed PTx solubility data were used to obtain Henry's law constants and
      correlated by three models: (1) the simple Krichevsky-Kasarnovsky (KK) equation,
      (2) a model comprised of the extended Henry's law and the Pitzer's virial
      expansion for the excess Gibbs free energy, and (3) the generic Redlich-Kwong
      (RK) cubic equation of state proposed for gas-ionic liquid systems. The
      correlations from the three models show quite good consistency with the
      experimental data for IL/CO(2) and IL/H(2)S binary mixtures within experimental
      uncertainties. For IL/CO(2)/H(2)S ternary mixtures, the RK model shows the best
      correlation with the experimental data. The comparison showed that the solubility
      of H(2)S is about two times as great as that of CO(2) in the ionic liquid studied
      in this work. It was further found, by comparison of the experimental data of
      this study with those of previous reports, that the solubility of H(2)S in
      [C(n)mim][Tf(2)N] ILs increases as the number of carbon atoms in the alkyl
      substituent of methylimidazolium cation, n, increases. In addition, quantum
      chemical calculations at DFT/B3LYP level of theory using 6-311+G(d) and 6
      311++G(2d,2p) basis sets were performed on the isolated systems studied in this
      work to provide explanations from a molecular point of view for the observed
      experimental trends.

PMID- 22372570
TI  - Corticosteroids and beta2-agonists upregulate mitogen-activated protein kinase
      phosphatase 1: in vitro mechanisms.
AB  - BACKGROUND AND PURPOSE: Airway remodelling is a consequence of long-term
      inflammation and MAPKs are key signalling molecules that drive pro-inflammatory
      pathways. The endogenous MAPK deactivator--MAPK phosphatase 1 (MKP-1)--is a
      critical negative regulator of the myriad pro-inflammatory pathways activated by
      MAPKs in the airway. EXPERIMENTAL APPROACH: Herein we investigated the molecular
      mechanisms responsible for the upregulation of MKP-1 in airway smooth muscle
      (ASM) by the corticosteroid dexamethasone and the beta2-agonist formoterol, added
      alone and in combination. KEY RESULTS: MKP-1 is a corticosteroid-inducible gene
      whose expression is enhanced by long-acting beta2-agonists in an additive manner.
      Formoterol induced MKP-1 expression via the beta2-adrenoceptor and we provide the
      first direct evidence (utilizing overexpression of PKIalpha, a highly selective
      PKA inhibitor) to show that PKA mediates beta2-agonist-induced MKP-1
      upregulation. Dexamethasone activated MKP-1 transcription in ASM cells via a cis
      acting corticosteroid-responsive region located between -1380 and -1266 bp of the
      MKP-1 promoter. While the 3'-untranslated region of MKP-1 contains adenylate +
      uridylate elements responsible for regulation at the post-transcriptional level,
      actinomycin D chase experiments revealed that there was no increase in MKP-1 mRNA
      stability in the presence of dexamethasone, formoterol, alone or in combination.
      Rather, there was an additive effect of the asthma therapeutics on MKP-1
      transcription. CONCLUSIONS AND IMPLICATIONS: Taken together, these studies allow
      us a greater understanding of the molecular basis of MKP-1 regulation by
      corticosteroids and beta2-agonists and this new knowledge may lead to elucidation
      of optimized corticosteroid-sparing therapies in the future.

PMID- 22372572
TI  - Maternal autonomy on health in a community as assessed by signing of consent for
      caesarean section and its sociodemographic correlates.
AB  - OBJECTIVE: To assess the level of maternal autonomy in a Nigerian community using
      maternal preference to sign the consent for caesarean section as the assessment
      tool and to evaluate the sociodemographic and obstetric correlates. METHODS: A
      cross-sectional survey of parturients 2-5 days after caesarean delivery in a
      tertiary health facility in Benin City, Nigeria using a pretested interviewer
      administered questionnaire to obtain information on whom they would prefer to
      sign the consent form for caesarean section. RESULTS: A total of 197 parturients
      were interviewed. The consent form was signed by 177 (90%) of the respondents.
      However, 96 (48.7%) preferred their spouses to sign. Maternal attainment of
      tertiary level education and a higher mean maternal age was significantly
      associated with maternal preference to sign the consent form. CONCLUSION: The
      level of maternal autonomy on reproductive health issues based on this simple
      survey is less than satisfactory. However, this study has provided baseline data
      for surveillance and follow-up studies of this important variable.

PMID- 22372573
TI  - Involvement of general practitioners in managing alcohol problems: a randomized
      controlled trial of a tailored improvement programme.
AB  - AIMS: To assess the effect of a tailored multi-faceted improvement programme on
      general practitioners' (GPs') behaviour towards prevention of hazardous and
      harmful alcohol consumption. The improvement programme consisted of activities
      aimed at the GP, organization and patient. Educational training sessions and
      visits by a facilitator were tailored to the GPs' needs and attitudes. DESIGN:
      Cluster randomized controlled trial. SETTING: General practices in the
      Netherlands. PARTICIPANTS: Seventy-seven general practices; 119 GPs participated.
      Data from 6318 patients were available, of whom 765 (12.1%) were at risk. A total
      of 1502 patients' electronic medical records were reviewed. MEASUREMENTS: The
      primary outcome was the number of eligible patients who received screening and
      advice. FINDINGS: Difficulties in recruiting GPs and in motivating GPs for
      participation in the tailored parts of the programme impeded optimal
      implementation of the programme. Although GPs in both groups became more involved
      after enrolment, this improvement waned during the trial. The quality improvement
      programme enhanced the initial improvement in behaviour and it tempered waning
      (intervention group), compared to our control condition, resulting in average
      improvement rates of 5% (screening) and 2% (advice-giving) at 12-month follow-up
      (not significant). CONCLUSIONS: A tailored, multi-faceted programme aimed at
      improving general practitioner management of alcohol consumption in their
      patients failed to show an effect and proved difficult to implement. There
      remains little evidence to support the use of such an intensive implementation
      programme to improve the management of harmful and hazardous alcohol consumption
      in primary care.

PMID- 22372574
TI  - Effects of naloxone on the breathing pattern of a newborn exposed to maternal
      opiates.
AB  - AIM: To give new insights into how an infant responded to naloxone, given after
      acquiring a maternal opiate by recording the breathing pattern directly after
      birth. METHOD: A respiratory recording is presented of an infant during
      resuscitation in the delivery room after receiving naloxone for respiratory
      depression, resulting from maternal remifentanyl use. RESULTS: The infant was
      born apneic and bradycardic. Normal resuscitation manoeuvres had no effect on the
      respiratory drive. Directly after administration of naloxone, a tachypneic
      breathing pattern with sporadic expiratory breaking manoeuvres was observed.
      CONCLUSION: The immediate tachypnoea is most likely a direct effect of the
      naloxone causing an immediate 'rebound response' after the release of the opiate
      induced inhibition of the respiratory drive.

PMID- 22372576
TI  - Direct conversion of porcine embryonic fibroblasts into adipocytes by chemical
      molecules.
AB  - Direct reprogramming of terminally differentiated cells to specify different cell
      types may allow somatic cells to be reprogrammed to an alternative,
      differentiated fate without intervening stem or progenitor cells. Recent studies
      have shown that the conversion of fibroblasts to other cell lines can be
      accomplished by the introduction of master regulator transcription factors. These
      findings have raised the question as to whether chemical molecules could replace
      transcription factor cocktails to directly alter defined somatic cell fate. Here,
      we demonstrate the generation of adipocytes directly from porcine embryonic
      fibroblasts (PEFs) using defined chemical molecules. Treatment with SB431542 and
      Thiazovivin, which are transforming growth factor-beta (TGF-beta) and ROCK
      signaling pathway inhibitors, respectively, allowed PEFs to directly convert to
      fat-laden adipocytes. These induced adipocytes expressed multiple fat marker
      genes. We believe that these findings demonstrate that committed adipocytes can
      be directly reprogrammed from differentiated somatic cells using defined chemical
      molecules. The generation of adipocytes from nonadipogenic lineages has important
      implications for studies of adipogenesis, obesity modeling, and regenerative
      medicine. Additionally, these findings may enlighten a new method that direct
      reprogramming committed cell lines to other somatic cells using defined chemical
      molecules.

PMID- 22372577
TI  - Roscovitine treatment improves synchronization of donor cell cycle in G0/G1 stage
      and in vitro development of handmade cloned buffalo (Bubalus bubalis) embryos.
AB  - This study investigated the effects of serum-starvation, total confluence, and
      roscovitine treatment on cell-cycle synchronization of buffalo ear skin
      fibroblasts to the G0/G1 stage and on the developmental competence of cloned
      embryos. Serum starvation of total confluence cultures for 24 h had a higher
      (p<0.05) proportion of cells at G0/G1 stage (94.4%) compared with serum starved
      cyclic and nonstarved confluent cultures (76.8 and 86.0%, respectively), whereas
      differences between cyclic cells with or without serum starvation were not
      significant. The proportion of cells at G0/G1 was higher (p<0.05) with 20 and 30
      MUM roscovitine treatment than that with 10 MUM (94.4, 96.4, and 86.6%,
      respectively), which was similar to that for total confluence (86.0%). MTT assay
      showed that cell viability decreased as dose of roscovitine increased. The
      blastocyst rate was significantly higher (p<0.05) when nuclear transfer embryos
      were reconstructed using donors cells from total confluence, confluence serum
      starved, and roscovitine-treated (20 and 30 MUM) groups (48.8, 48.9, 57.9, and
      62.9%, respectively) compared to nontreated cyclic cells (20.2%). However, the
      cleavage rate and total cell number of cloned embryos were similar for all the
      groups. The number of ICM cells was improved by 30 MUM roscovitine treatment
      (45.25 +/- 2.34). The cryosurvival rate of blastocysts derived from cells
      synchronized with 20 or 30 MUM roscovitine was higher compared to that for total
      confluence group (33.6, 37.8 vs. 23.8%). In conclusion, treatment with 30 MUM
      roscovitine is optimal for harvesting G0/G1 stage cells for producing high
      quality cloned buffalo embryos, and that it is better than serum-starvation or
      total confluence for cell synchronization.

PMID- 22372575
TI  - Valproic acid improves the in vitro development competence of bovine somatic cell
      nuclear transfer embryos.
AB  - The present study was carried out to examine the effect of valproic acid (VPA),
      an important histone deacetylase inhibitor, on the in vitro development and
      expression of the epigenetic marker histone H3 lysine 9 (H3K9ac) in bovine
      somatic cell nuclear transfer (SCNT) embryos. We found that treatment with 4 mM
      VPA for 24 h could significantly improve the development of bovine SCNT embryos.
      Compared with the no-treatment group, the cleavage rate was higher (69.79 +/-
      0.99% vs. 65.11 +/- 1.02%, p<0.05), as was the blastocyst rate (39.99 +/- 1.29%
      vs. 34.87 +/- 1.74%, p<0.05). Moreover, the rate of apoptosis (1.91 +/- 0.48% vs.
      5.67 +/- 0.40%, p<0.05) in blastocysts was greatly reduced after VPA treatment.
      Valproic acid treatment also increased the immunofluorescent signal for H3K9ac in
      SCNT embryos in a pattern similar to that of in vitro fertilized (IVF) embryos.
      In conclusion, we demonstrated that VPA can significantly improve the in vitro
      developmental competence and enhance the nuclear reprogramming of bovine SCNT
      embryos.

PMID- 22372578
TI  - Rapid genetic change underpins antagonistic coevolution in a natural host
      pathogen metapopulation.
AB  - Antagonistic coevolution is a critical force driving the evolution of diversity,
      yet the selective processes underpinning reciprocal adaptive changes in nature
      are not well understood. Local adaptation studies demonstrate partner impacts on
      fitness and adaptive change, but do not directly expose genetic processes
      predicted by theory. Specifically, we have little knowledge of the relative
      importance of fluctuating selection vs. arms-race dynamics in maintaining
      polymorphism in natural systems where metapopulation processes predominate. We
      conducted cross-year epidemiological, infection and genetic studies of multiple
      wild host and pathogen populations in the Linum-Melampsora association. We
      observed asynchronous phenotypic fluctuations in resistance and infectivity among
      demes. Importantly, changes in allelic frequencies at pathogen infectivity loci,
      and in host recognition of these genetic variants, correlated with disease
      prevalence during natural epidemics. These data strongly support reciprocal
      coevolution maintaining balanced resistance and infectivity polymorphisms, and
      highlight the importance of characterising spatial and temporal dynamics in
      antagonistic interactions.

PMID- 22372579
TI  - Technical note: Evaluation of tined endoscopically placed mucosal leads for
      temporary gastric neurostimulation.
AB  - OBJECTIVE: To compare larger diameter corkscrew-tined leads with previously
      described intracardiac pacing leads for temporary gastric neurostimulation in a
      canine model. MATERIALS AND METHODS: Two mongrel dogs underwent gastroscopy under
      general anesthesia, with endoscopic placement of two cardiac leads (1 mm tine
      diameter, 4 mm depth) placed sequentially in 1) transverse configuration in the
      distal antrum mucosa; 2) longitudinal (1 cm apart) configuration in gastric
      corpus. Stomach was then stimulated with maximal parameters to induce neutrally
      mediated contraction. Procedures were then repeated with larger leads (5 mm tine
      diameter, 8 mm length). Gastric contractions were measured with serosal strain
      transducers. RESULTS: Leads were placed endoscopically without difficulty.
      Neither lead type punctured through to the serosa of the stomach. Neither cardiac
      nor larger leads were capable of eliciting any gastric contractile activity with
      endoscopic placement either in the transverse or longitudinal orientations.
      DISCUSSION: While successful on the serosal side, both the cardiac leads and the
      larger alternative leads failed to produce stomach contraction when implanted
      mucosally. This may be due to the elastic nature of the mucosa, which was
      observed to twist around both types of leads significantly, hindering proper
      penetration into the muscularis. CONCLUSION: These results suggest that the
      current concept of temporary gastric electrical neurostimulation via a mucosal
      approach must be reevaluated, as the procedure most likely does not accurately
      mimic electrical stimulation in the muscularis.

PMID- 22372580
TI  - Inter- and intra-observational variability in immunohistochemistry: a multicentre
      analysis of diffuse large B-cell lymphoma staining.
AB  - AIMS: Although many immunohistochemical (IHC) cancer biomarkers have been
      identified, very few have translated into routine clinical practice, primarily
      because of technical and observational inconsistencies between studies. However,
      despite the obvious need to address such variability, very few studies have done
      so. METHODS AND RESULTS: Using bcl-6, CD10, MUM1, GCET1 and FOXP1 antibody
      staining on diffuse large B-cell lymphoma cases (n = 138) as a model, we employed
      Cronbach alpha analysis to quantify interobserver and intraobserver variability
      between four independent observers (two per institution), scoring two tissue
      microarrays (TMAs) stained at both institutions using differing staining
      procedures. The overall concordance between all observations irrespective of
      staining procedure or TMA source was high (average alpha = 0.951), with the
      highest level being reached for CD10 staining (average alpha = 0.967) and the
      lowest for bcl-6 (average alpha = 0.924). Interslide and interinstitutional
      reproducibility were similarly high (average alpha = 0.952 and average alpha =
      0.934, respectively). Interobserver/intrainstitutional and
      interobserver/interinstitutional comparisons showed lower levels of concordance
      (average alpha = 0.870 and average alpha = 0.877, respectively), and
      intraobserver/interinstitutional comparisons showed the lowest levels of
      concordance (average alpha = 0.810), particularly for bcl-6 staining (alpha =
      0.658). CONCLUSIONS: This study suggests that most variability in IHC studies
      between centres results from inherent limitations of the biomarkers investigated
      rather than procedural or observational differences.

PMID- 22372581
TI  - Tacrolimus as a risk factor for tuberculosis and outcome of treatment with
      rifampicin in solid organ transplant recipients.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence, risk
      factors, and treatment outcome of tuberculosis (TB) in solid organ transplant
      (SOT) recipients treated with rifampicin. METHODS: The incidence density of TB
      was calculated by a retrospective cohort study. Risk factors for TB were analyzed
      by a nested case-control study. Treatment outcome and effects of anti-TB drugs on
      immunosuppressants and allograft were compared between patients whose initial 2
      month intensive regimen included rifampicin and those whose intensive regimen did
      not. RESULTS: Among the 2144 SOT recipients over 16 years, 40 cases of TB were
      found (1.7%). The incidence density was 372 cases per 10(5)  patient years (95%
      confidence interval [CI], 270-503), which was 4 times higher than for the general
      Korean population (90 cases per 10(5)  person years). The median time to the
      development of TB was 234 days (range, 33-3940 days). The use of tacrolimus (odds
      ratio [OR] 4.90; 95% CI, 1.74-13.80; P = 0.003) and cytomegalovirus (CMV)
      infection within the prior 3 months (OR 4.62; 95% CI, 1.44-14.87; P = 0.01) were
      found to be risk factors for TB. Patients whose intensive regimen included
      rifampicin were more likely to have an increased dose of calcineurin inhibitors
      than patients whose intensive regimen did not include rifampicin (13/15 [86.7%]
      vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ
      between the 2 groups. CONCLUSIONS: Use of tacrolimus and CMV infection were major
      risk factors for TB in SOT recipients. The graft outcome and mortality did not
      differ whether rifampicin was used or not during the first 2-month intensive
      phase.

PMID- 22372582
TI  - 1,1-Carboboration route to substituted naphthalenes.
AB  - 1,2-Bis(alkynyl)benzene derivatives react with strongly electrophilic boranes to
      yield in boryl-functionalized bulky naphthalene derivatives by means of a
      sequence of 1,1-carboboration reactions. These substrates can be functionalized
      by transition metal catalyzed cross-coupling reactions.

PMID- 22372583
TI  - Temozolomide in the management of dopamine agonist-resistant prolactinomas.
AB  - BACKGROUND: The majority of prolactinomas respond to dopamine agonist therapy,
      but a proportion are resistant, requiring other treatments including surgery
      and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been
      used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas,
      including prolactinomas, unresponsive to all conventional treatment. CASE SERIES:
      We report three patients where temozolomide was used in the treatment of
      refractory prolactinomas. Case 1 describes a patient with a highly invasive
      prolactinoma, resistant to all conventional therapy, which responded dramatically
      to temozolomide used as a salvage treatment. In case 2, temozolomide was used
      after incomplete surgical resection to relieve chiasmal compression and avoid
      chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to
      be deferred in a 16-year old with a resistant prolactinoma. In all three cases,
      the tumours were negative by immunostaining for methylguanine methyltransferase
      (MGMT). LITERATURE REVIEW AND DISCUSSION: A review of the published literature
      reveals 51 reported cases of temozolomide treatment for pituitary tumours,
      including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good
      response to temozolomide. Our analysis demonstrates a strong association between
      MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030).
      Current clinical practice is to use temozolomide as a salvage therapy after all
      conventional modalities of treatment have failed. We suggest that, in selected
      cases, consideration should be given to using temozolomide earlier in the
      treatment algorithm.

PMID- 22372584
TI  - A retrospective study of diabetic foot ulcers treated with hyperbaric oxygen
      therapy.
AB  - A retrospective review of patient medical records was conducted to assess what
      factors influence the outcomes of diabetic foot ulcers treated with hyperbaric
      oxygen (HBO) therapy. Patients referred to the Diving Diseases Research Centre
      for HBO therapy for the treatment of diabetic foot ulcers during a 2-year period
      were included in this study. Data collected from 30 sets of patient records were
      entered into SPSS and statistical analysis was undertaken to investigate whether
      any underlying pathologies or confounding factors appeared to influence patient
      outcome. A 73.3% of patients achieved a successful outcome of partial healing,
      major amputation no longer required, amputation level lower than anticipated
      prior to HBO or healing at the end of HBO therapy and 70% remained successful 3
      months later. A 13.3% of patients were lost to follow-up at 3 months and one
      patient (3.3%) had a major amputation. Steroid therapy, peripheral vascular
      disease, previous minor amputation, type of diabetes, previous HBO therapy,
      larvae therapy, the use of interactive dressings and haemoglobin A1c levels were
      all observed to have had a significant relationship with patient outcome (P <
      0.05). These results were compared with data from other published research
      conducted in this area on similar patient groups. A larger scale study focussing
      on the factors found to be significant in this study is recommended. An
      improvement of patient documentation would allow patient outcomes to be more
      consistently monitored in the future.

PMID- 22372585
TI  - Reversibly tunable lower critical solution temperature utilizing host-guest
      complexation of pillar[5]arene with triethylene oxide substituents.
AB  - A thermoresponsive macromolecule consisting of 10 outer triethylene oxide groups
      and a pillar[5]arene core was prepared. The macromolecule showed lower critical
      solution temperature behavior. Moreover, its clouding point can be reversibly
      tuned based on the addition of guest and host compounds; the clouding point
      increased upon addition of a guest didecylviologen salt and decreased when the
      competitive host cucurbit[7]uril was added.

PMID- 22372586
TI  - On the potential of lower limb muscles to accelerate the body's centre of mass
      during walking.
AB  - Quantification of lower limb muscle function during gait or other common
      activities may be achieved using an induced acceleration analysis, which
      determines the contributions of individual muscles to the accelerations of the
      body's centre of mass. However, this analysis is reliant on a mathematical
      optimisation for the distribution of net joint moments among muscles. One
      approach that overcomes this limitation is the calculation of a muscle's
      potential to accelerate the centre of mass based on either a unit-force or
      maximum-activation assumption. Unit-force muscle potential accelerations are
      determined by calculating the accelerations induced by a 1 N muscle force,
      whereas maximum-activation muscle potential accelerations are determined by
      calculating the accelerations induced by a maximally activated muscle. The aim of
      this study was to describe the acceleration potentials of major lower limb
      muscles during normal walking obtained from these two techniques, and to evaluate
      the results relative to absolute (optimisation-based) muscle-induced
      accelerations. Dynamic simulations of walking were generated for 10 able-bodied
      children using musculoskeletal models, and potential- and absolute induced
      accelerations were calculated using a perturbation method. While the potential
      accelerations often correctly identified the major contributors to centre-of-mass
      acceleration, they were noticeably different in magnitude and timing from the
      absolute induced accelerations. Potential induced accelerations predicted by the
      maximum-activation technique, which accounts for the force-generating properties
      of muscle, were no more consistent with absolute induced accelerations than unit
      force potential accelerations. The techniques described may assist treatment
      decisions through quantitative analyses of common gait abnormalities and/or
      clinical interventions. 

PMID- 22372587
TI  - The protective effects of quercetin on the cytotoxicity of atrazine on rat
      Sertoli-germ cell co-culture.
AB  - To evaluate the direct effect of atrazine (ATZ) and the protective effect of
      quercetin (QT) on testicular cells, we used primary cultures of rat Sertoli-germ
      cells (SGCs). ATZ (232 MUm) up-regulated the mRNA expression of GATA-4, androgen
      receptor (AR), androgen-binding protein (ABP), steroidogenic acute regulatory
      protein (StAR), cytochrome P450 side-chain cleavage enzyme (CYP11A1),
      cyclooxygenase-2 (COX-2) and NF-kappaappaB (NF-kappaB) and down-regulated the
      expression of stem cell factor (SCF) mRNA. There was no change on the mRNA
      expression of oestrogen receptor-alpha (ER-alpha). Simultaneous supplementation
      of QT in the culture normalizes the expression of these genes. The stimulatory
      action of follicle stimulating hormone (10 ng/mL) on ATZ-induced StAR and CYP11A1
      mRNA levels were also prevented by QT. Furthermore, ATZ-stimulatory action on AR
      mRNA was opposed in a dose-dependent manner in the presence of increasing
      concentrations of QT (10-50 MUm).The dislodgement of germ cells from the Sertoli
      cells monolayer and decrease in SGCs viability was prevented by QT. To show
      whether or not the disrupted interactions of Sertoli and germ cells impaired
      spermatogenesis, adult male rats exposed in vivo to ATZ (50 mg/kg b.wt) for 1
      week had their daily spermatozoa production (DSP) per gram testis lowered by 30%.
      DSP was significantly increased in the QT(10 mg/kg) + ATZ-treated rats as
      compared with the ATZ-treated rats. Taken together, ATZ can alter SGCs expression
      of spermatogenesis- and steroiodogenesis-related genes resulting in a decrease in
      sperm production in the testis as well as cell viability. QT might block these
      molecular events-induced by ATZ thereby protecting testicular Sertoli-germ cells
      from ATZ-induced toxicity.

PMID- 22372588
TI  - Medical responsibility in the operating room: the example of an amniotic fluid
      embolism.
AB  - Amniotic fluid embolism (AFE) continues to be one of the most feared
      complications of pregnancy. A healthy 32-year-old woman died during delivery
      after a normal 39-week third pregnancy. The family filed a complaint with a
      criminal court as the causes of death appeared unclear. No risk factor associated
      with AFE was identified. Clinical presentation was typical, including sudden
      onset of cardiovascular and respiratory symptoms. Autopsy confirmed the
      histological diagnosis of amniotic embolism and excluded an iatrogenic cause of
      death or anesthetic malpractice. This article highlights the value of both
      antemortem records and histological features in establishing the diagnosis of AFE
      and demonstrates the fundamental importance of autopsy in an unexpected death
      related directly or indirectly to a medical procedure.

PMID- 22372589
TI  - Improving prevention and treatment of venous thromboembolism: clinical trial
      results.
AB  - BACKGROUND: Venous thromboembolism (VTE) incurs considerable socioeconomic costs,
      partly owing to the fact that the treatment and prevention of VTE via effective
      thromboprophylaxis remains suboptimal in the inpatient and outpatient settings of
      many healthcare systems. A number of organizations-including the National Quality
      Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services
      have established measures to assess and reduce the healthcare burden of VTE.
      These improvement strategies focus on increasing the use of thromboprophylaxis,
      implementing existing guidelines, and improving awareness. FINDINGS: Based on
      clinical trial results, the oral anti-coagulants rivaroxaban, apixaban, and
      dabigatran etexilate have been approved in many countries for the prevention of
      VTE in patients after elective hip or knee replacement surgery. Recently,
      dabigatran etexilate and rivaroxaban have also been approved in the US for the
      prevention of stroke and systemic embolism in patients with non-valvular atrial
      fibrillation. In addition, rivaroxaban is currently the only newer anti-coagulant
      that has been approved in Europe for the treatment of deep vein thrombosis and
      for the long-term prevention of recurrent VTE. These oral anti-coagulants have
      several advantages over established anti-coagulants, including no need for
      routine coagulation monitoring and only minimal food and drug interactions. These
      characteristics, together with convenient oral administration, may improve
      adherence and quality of life for patients, which could result in reductions in
      the rate of VTE. CONCLUSIONS: These three oral agents have several advantages
      over established anti-coagulants and could, therefore, address the unmet needs of
      patients, physicians, and healthcare systems, with the potential to reduce the
      burden of anti-coagulant management and the occurrence of VTE.

PMID- 22372590
TI  - Sociocultural input facilitates children's developing understanding of
      extraordinary minds.
AB  - Three- to 5-year-old (N = 61) religiously schooled preschoolers received theory
      of-mind (ToM) tasks about the mental states of ordinary humans and agents with
      exceptional perceptual or mental capacities. Consistent with an anthropomorphism
      hypothesis, children beginning to appreciate limitations of human minds (e.g.,
      ignorance) attributed those limits to God. Only 5-year-olds differentiated
      between humans' fallible minds and God's less fallible mind. Unlike secularly
      schooled children, religiously schooled 4-year-olds did appreciate another
      agent's less fallible mental abilities when instructed and reminded about those
      abilities. Among children who understood ordinary humans' mental fallibilities,
      knowledge of God predicted attributions of correct epistemic states to
      extraordinary agents. Results suggest that, at a certain point in ToM
      development, sociocultural input can facilitate an appreciation for extraordinary
      minds.

PMID- 22372591
TI  - Effects of oestrogen and testosterone therapy on serum metabolites in
      postmenopausal women.
AB  - OBJECTIVES: Metabolite profiles of body fluids or tissue extracts can be regarded
      as important indicators of physiological or pathological states. Whether hormone
      specific alterations of the serum metabolome can be identified using this
      technique has not been tested yet. The aim of this study was to investigate
      metabolic responses during hormone therapy in postmenopausal women by a
      nontargeted metabolomics approach. METHODS: Sixty naturally postmenopausal women
      were randomly assigned to treatment with testosterone undecanoate 40 mg every
      second day; estradiol valerate 2 mg daily; or the combination of both. Serum
      metabolites were determined by gas chromatography-mass spectrometry (GC-MS)
      before and after 3 months of treatment. Metabolites affected by the treatment
      were identified and correlated with changes in insulin sensitivity and lipid
      profiles. RESULTS: Treatment-dependent and hormone-specific effects on serum
      metabolites were observed, ranging between 69% reduction and 184% increase, but
      the metabolites that best explained the differences could not be structurally
      identified. Effects on annotated metabolites were less associated with clinical
      parameters as compared to established serum markers for adverse lipid and
      carbohydrate metabolism, such as cholesterol and triglycerides. However, cystine,
      lysine and tyrosine were shown to change in correlation with insulin sensitivity
      and high-density lipoprotein cholesterol levels in response to testosterone,
      indicating that those responses were somehow related to each other. CONCLUSIONS:
      Oestrogen- and androgen-specific alterations in the serum metabolome could be
      identified using GC-MS, reflecting hormone-specific effects on whole body
      metabolism. New knowledge regarding steroid-mediated metabolic responses within
      different tissues might be obtained using a similar approach on tissue extracts.

PMID- 22372592
TI  - Structural heterogeneity and unique distorted hydrogen bonding in primary
      ammonium nitrate ionic liquids studied by high-energy X-ray diffraction
      experiments and MD simulations.
AB  - Liquid structure and the closest ion-ion interactions in a series of primary
      alkylammonium nitrate ionic liquids [C(n)Am(+)][NO(3)(-)] (n = 2, 3, and 4) were
      studied by means of high-energy X-ray diffraction (HEXRD) experiments with the
      aid of molecular dynamics (MD) simulations. Experimental density and X-ray
      structure factors are in good accordance with those evaluated with MD
      simulations. With regard to liquid structure, characteristic peaks appeared in
      the low Q (Q: a scattering vector) region of X-ray structure factors S(Q)'s for
      all ionic liquids studied here, and they increased in intensity with a peak
      position shift toward the lower Q side by increasing the alkyl chain length.
      Experimentally evaluated S(Q(peak))(r(max)) functions, which represent the S(Q)
      intensity at a peak position of maximum intensity Q(peak) as a function of
      distance (actually a integration range r(max)), revealed that characteristic
      peaks in the low Q region are related to the intermolecular anion-anion
      correlation decrease in the r range of 10-12 A. Appearance of the peak in the low
      Q region is probably related to the exclusion of the correlations among ions of
      the same sign in this r range by the alkyl chain aggregation. From MD
      simulations, we found unique and rather distorted NH...O hydrogen bonding between
      C(n)Am(+) (n = 2, 3, and 4) and NO(3)(-) in these ionic liquids regardless of the
      alkyl chain length. Subsequent ab initio calculations for both a molecular
      complex C(2)H(5)NH(2)...HONO(2) and an ion pair C(2)H(5)NH(3)(+)...ONO(2)(-)
      revealed that such distorted hydrogen bonding is specific in a liquid state of
      this family of ionic liquids, though the linear orientation is preferred for both
      the N...HO hydrogen bonding in a molecular complex and the NH...O one in an ion
      pair. Finally, we propose our interpretation of structural heterogeneity in PILs
      and also in APILs.

PMID- 22372593
TI  - Cell therapy in the heart.
AB  - Cell therapy is emerging as a new strategy to circumvent the adverse effects of
      heart disease. Many experimental and clinical studies investigating the
      transplantation of cells into the injured myocardium have yielded promising
      results. Moreover, data from these reports show that transplanted stem cells can
      engraft within the myocardium, differentiate into major cardiac cell types, and
      improve cardiac function. However, results from clinical trials show conflicting
      results. These trials demonstrate significant improvements in cardiac function
      for up to 6 months. However, these improved functions were diminished when
      examined at 18 months. In this review, we will discuss the current literature
      available on cell transplantation, covering studies ranging from animal models to
      clinical trials.

PMID- 22372595
TI  - Status of sex reassignment surgery for gender identity disorder in Japan.
AB  - An incongruence between one's physiological sex and the gender identity that is
      one's basic sense of self as a man or a woman is known as gender identity
      disorder. In general, the conditions of physiological men having female gender
      identity and physiological women having male gender identity are called male-to
      female and female-to-male gender identity disorder, respectively. Although the
      precise pathogenesis of gender identity disorder remains unclear, the prevalence
      of gender identity disorder is quite high, with the rates calculated for male-to
      female to be 1:25,000 and female-to-male to be 1:12,000 in Hokkaido, Japan. The
      diagnosis and treatment of gender identity disorder in Japan are based on the
      Diagnostic and Therapeutic Guidelines for Patients with Gender Identity Disorder,
      4th edition. Although gender identity disorder was previously thought to be a
      psychiatric condition, it is extremely difficult to assign gender identity to
      physiological sex by psychiatric and psychological treatments. To adapt the
      figure of the body to the native gender identity, physical treatments such as
      administration of cross-sex steroids and sex reassignment surgery are considered.
      However, there are very few institutions that routinely carry out sex
      reassignment surgery in Japan, even though it is mandatory for changing sex on
      the census register at the present time. Sex reassignment surgery for male-to
      female and female-to-male patients includes orchiectomy, penectomy,
      clitoroplasty, vaginoplasty and vulvoplasty, and hysterectomy, ovariectomy,
      metoidioplasty and phalloplasty, respectively. To provide accurate information
      about physical treatment for patients with gender identity disorder, even
      urologists who are not actively involved in the diagnosis and treatment of gender
      identity disorder should understand the fundamental aspects and contemporary
      problems of gender identity disorder.

PMID- 22372596
TI  - Aged regulatory T cells protect from autoimmune inflammation despite reduced
      STAT3 activation and decreased constraint of IL-17 producing T cells.
AB  - Regulatory T cells (Tregs) are specialized CD4(+)  T lymphocytes helping defend
      against autoimmunity and inflammation. Although age is associated with increased
      inflammation and autoimmunity, few reports address age effects of immune
      regulation or auto-aggressive T cells. We show here that young and aged naive
      CD4(+)  T cells are equivalently auto-aggressive in vivo in T cell-driven
      autoimmune colitis. Young and aged CD4(+)  Tregs equally suppressed age-matched T
      cell proliferation in vitro and controlled clinical and pathologic T cell-driven
      autoimmune colitis, suggesting equivalent regulatory function. However, whereas
      young and aged CD4(+)  Tregs suppressed interferon (IFN)-gamma(+)  T cells
      equivalently in this model, aged CD4(+)  Tregs unexpectedly failed to restrain
      interleukin (IL)-17(+)  T cells. Nonetheless, young and aged CD4(+)  Tregs
      equally restrained IL-17(+)  T cells in vivo during acute inflammation,
      suggesting a chronic inflammation-related defect in aged CD4(+)  Tregs. In
      support, aged Tregs expressed reduced STAT3 activation, a defect associated with
      poor IL-17-producing T cell restraint. Aged naive mice had markedly increased
      programmed death (PD)-1(+)  T cells, but these exhibited no significant auto
      aggressive or regulatory functions in T cell-driven colitis. Young CD8(+)  CD122(
      )  T cells induce autoimmune bone marrow failure, but we show that aged CD8(+) 
      CD122(-)  T cells do not. These data demonstrate no apparent age-related increase
      in auto-aggressive T cell behavior, but disclose previously unrecognized
      functional defects in aged CD4(+)  Tregs during chronic inflammation. IL-17 can
      be inflammatory and contributes to certain autoimmune disorders. Reduced aged
      Treg function during chronic inflammation and reduced IL-17 restraint could
      contribute to age-related inflammation or autoimmunity.

PMID- 22372597
TI  - Computerised system for measurement of muscle thickness based on ultrasonography.
AB  - In this paper, a computerised system for measuring muscle thicknesses of the
      transverse abdominus (TrA), internal oblique and external oblique muscles based
      on ultrasonography is presented. The system is designed to allow for quantitative
      analysis of changes in muscle recruitment and activity, which facilitates the
      study of such changes and its relationship with low back pain. The abdominal
      muscle area was localised and imaged under different standing conditions using B
      mode ultrasonography. To account for issues such as misalignments due to probe
      and subject motion as well as speckle noise inherent to ultrasonography,
      automatic ensemble registration is performed on the acquired images using a
      sequential quadratic programming approach based on a novel log-Rayleigh
      likelihood function. Regions of interest are then automatically identified based
      on the medial border of the TrA for the purpose of quantitative muscle thickness
      measurements. Experimental results show that the proposed system achieves
      registration errors of under 0.4 mm when compared with ground-truth measurements,
      as well as allow for the measurement of muscle thickness changes in the
      millimetre range. The proposed system is currently in operational use as an
      analysis tool for studying the relationship between abdominal muscle thickness
      changes and postural changes.

PMID- 22372598
TI  - Home care in Italy: a system on the move, in the opposite direction to what we
      expect.
AB  - For a long time, the international literature has described the Italian public
      system of home care for frail elderly people as underfunded and mostly cash
      oriented; a system, thus, relying almost entirely on informal care provided by
      the family and, more recently, by migrant workers. Abroad and in Italy, most
      experts have long shared the expectation that, if and when, public expenditure
      devoted to home care was to increase, the outcome would be an expansion in the
      provision of services in kind. This study analyses how the provision of home care
      actually has changed in the last decade. The analysis reveals that indeed public
      expenditure has risen. However, while the system of home-care provision also has
      changed, it has done so in the opposite direction to that expected. In fact, most
      of the additional resources have funded an increase in the number of users of the
      companion payment [Indennita di Accompagnamento (IA)], a cash benefit of ?487 per
      month. In this respect, the Italian welfare system is more cash-oriented than it
      was 10 years ago. This article discusses the reasons behind the increased uptake
      of the IA, namely: an increase in the needs and demands of older people; the
      traits of the Italian welfare system; and the peculiar features of the companion
      payment itself. The article then looks at why services in kind rose to a lesser
      degree, pinpoints the main reason as being based on the politics of social care
      at national level, and finally focuses on the challenges that the Italian home
      care system has to face within the changed policy environment with respect to
      quality of care, carers' conditions and support for users with high-level needs.

PMID- 22372599
TI  - Expenditure of chronic venous leg ulcer management in German primary care:
      results from a population-based study.
AB  - The aim of the study was to determine the demand on health service utilisation
      and to estimate the therapeutical costs caused by patients with chronic leg ulcer
      (CLU) in German primary care. A population-based case-control study was conducted
      using electronic medical records of 116 059 patients extracted from the CONTENT
      primary care database of Heidelberg, Germany, between April 2007 and March 2010.
      The drug and non drug prescription rates among patients with CLU were analysed by
      means of a unified German identification key and compared with those of patients
      with chronic venous insufficiency (CVI) without CLU. In the 3-year-contact group,
      CLU patients had significantly more patient-doctor encounters (55.9 versus 40.3;
      p < 0.0001), more referrals to home-care services (6.12 versus 3.08; p < 0.0001),
      and more admissions to hospitals (0.9 versus 0.4; p < 0.0001) than CVI patients,
      but no difference in referrals to specialists. The annual treatment costs for
      drugs and non drugs in CLU patients were substantially higher than in CVI
      patients (1645.75 ? versus 1188.17 ?; p < 0.0001). Wound dressings were
      identified as the most cost-enlarging factor. Summarising, CLU patients in
      primary care settings place a higher demand on health service utilisation and
      need nearly one-third higher therapeutical costs compared to venous patients
      without ulceration.

PMID- 22372600
TI  - Balaglitazone: a second generation peroxisome proliferator-activated receptor
      (PPAR) gamma (gamma) agonist.
AB  - Balaglitazone (DRF-2593) is a novel partial agonist of PPAR-gamma (gamma), which
      is developed by Dr. Reddy's laboratories India. Balaglitazone is a second
      generation peroxisome proliferator-activated receptor (PPAR) gamma agonist with
      only partial agonistic properties. Balaglitazone is currently being evaluated in
      phase III clinical trial in United States and Europe. Selective PPAR-gamma
      modulators bind in distinct manners to the ligand-binding pocket of PPAR-gamma,
      leading to alternative receptor conformations, differential cofactor
      recruitment/displacement, differential gene expression, and ultimately
      differential biological responses. Based on this concept, new and improved novel
      antidiabetic agents are in current development. Clinical studies conducted with
      409 subjects of randomized, double blind, parallel-group placebo and active
      comparator-controlled subject groups to determine the efficacy and safety of
      Balaglitazone. The study showed that the trial met its primary endpoint.
      Balaglitazone treated groups shown significantly reduce of HbA1c (%), FSG
      (mmol/L), postprandial glucose as comparison to pioglitazone. Phase III clinical
      studies data clearly shows that Balaglitazone provides robust glycemic control as
      an add-on to insulin therapy. Balaglitazone 10 mg and 20 mg show the similar
      magnitudes of the effects which comparable to the effects seen in the
      pioglitazone 45 mg group. The incidence of fluid retention and fat accumulation
      fewer than those observed with pioglitazone 45 mg. Hence, Balaglitazone is
      prominent candidate of new glitazone which requires fewer doses as comparison
      pioglitazone and shows better safety profile less incidence of special adverse
      effect like heart failure, peripheral oedema, and myocardial infarction. Unlike
      other marketed PPAR gamma agonists, Balaglitazone shows less fluid retention,
      less heart enlargement and no reduction of bone formation than full PPAR gamma
      agonists in preclinical studies. In present review, we have tried to cover
      classification PPARs various ligands, chemistry, physical properties, commercial
      synthesis, current patent status, polymorphic information, receptor interaction,
      pharmacophore rational, mechanism, adverse effect and clinical status of
      Balaglitazone, giving emphasis on medicinal chemistry aspect.

PMID- 22372601
TI  - Indolinones as promising scaffold as kinase inhibitors: a review.
AB  - Kinases are probably the most important signaling enzymes, which represent about
      20% of the druggable genome. Currently, more than 150 kinases are known. So,
      kinase inhibition therapy has become a very important area of drug research since
      most of our diseases are related to intra or intercellular signaling by kinases.
      Indole alkaloids are extensively studied for their biological activities in
      several pharmaceutical areas, including, for example, antitumor. Among this
      chemical family, indolinone displays very promising antitumor properties by
      inhibiting various kinase families. These small molecules have a low molecular
      weight and most of them bind to protein kinases competing with ATP for the ATP
      binding site. This review focuses on the indolinone based drugs approved for the
      treatment of cancer, drugs under clinical trial and then chemical diversity of
      various synthetic analogues of indolinone and their metabolites as various kinase
      inhibitors. This review also focused on structural activity relationship (SAR),
      mechanisms of action and biological targets through which indolinone and its
      derivatives display their antitumor activity.

PMID- 22372602
TI  - Effects of tea polyphenols and their polymers on MAPK signaling pathways in
      cancer research.
AB  - The biological activities and mechanisms of tea polyphenols and their polymerics
      have been attractive issues in cancer research. The inhibition of tea polyphenols
      on cancer cells decreased cell proliferation and increased apoptosis. Tremendous
      evidences have shown that tea polyphenols suppress tumor promotion by inhibiting
      enzyme activities and blocking signal transduction pathways. Specifically, the
      mitogen activated protein kinases (MAPK) pathways have been implicated as an
      important target molecular for cancer prevention and therapy. The purpose of this
      review is to discuss the relationship between tea polyphenols and MAPK signaling
      pathways in cancer.

PMID- 22372603
TI  - Chemical and bioactive diversities of the genus Chaetomium secondary metabolites.
AB  - The genus Chaetomium fungi are considered to be a rich source of novel and
      bioactive secondary metabolites of great importance. Up till now, a variety of
      more than 200 secondary metabolites belonging to diverse structural types of
      chaetoglobosins, epipolythiodioxopiperazines, azaphilones, xanthones,
      anthraquinones, chromones, depsidones, terpenoids, and steroids have been
      discovered. Most of these fungal metabolites exhibited antitumor, cytotoxic,
      antimalarial, enzyme inhibitory, antibiotic, and other activities. This review
      covers the extraction, structure elucidation, structural diversity, and
      biological activities of natural products isolated from about 30 fungi associated
      with marine- and terrestrial- origins, and highlights some bioactive compounds as
      well as their mechanisms of action and structure-activity relationships.

PMID- 22372604
TI  - The impact of hyaluronan on monocyte Toll-like receptor expression in term infant
      cord blood.
AB  - AIM: To explore the possible effects of hyaluronan, an endogenous mediator of
      inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in
      human umbilical cord blood ex vivo, and in a model mimicking Gram-negative
      neonatal sepsis. METHODS: Term infant cord blood was obtained after elective
      caesarean sections, n = 15. Both unstimulated and lipopolysaccharide-stimulated
      (10 ng/mL) blood was incubated with 500 MUg/mL high- or low-molecular-weight
      hyaluronan for 6 h. Expression of Toll-like receptors 2 and 4 on monocytes was
      measured using flow cytometry, and plasma concentrations of proinflammatory
      cytokines and matrix metalloproteinase 9 were analysed. RESULTS (MEAN +/- SEM):
      We found a significant decrease in Toll-like receptor 4 expression in the
      presence of high-molecular-weight hyaluronan (HMW HA) in unstimulated blood
      (median fluorescence intensity 141 +/- 7.3 vs. 163 +/- 9.8, p = 0.019). There
      were no significant changes in Toll-like receptor 2 expression. Levels of
      cytokines and matrix metalloproteinase 9 increased in the presence of both forms
      of hyaluronan. CONCLUSIONS: Our results confirm that hyaluronan affects the
      neonatal immune response. The biological significance of these findings requires
      further clarification. More studies are needed to validate the possible down
      modulation of Toll-like receptor 4 exerted by HMW HA.

PMID- 22372605
TI  - High prevalence of micropenis in 2710 male newborns from an intensive-use
      pesticide area of Northeastern Brazil.
AB  - Exposure to endocrine-disrupting chemicals (EDCs) has been suggested to
      contribute to the increasing trends of external genital malformation in male
      newborns. In Northeastern Brazil, the poor sanitary conditions found in the
      favelas encourage the widespread use of pesticides. This 2-year study of a total
      birth cohort of full-term male newborns in the regional hospitals of Campina
      Grande (Paraiba, Brazil) sought to (1) accurately establish for the first time
      the incidences of neonatal male genital malformations, (2) investigate the
      endocrine and genetic aetiologies of these malformations, and (3) evaluate their
      associations with possible prenatal exposure to EDCs. A total of 2710 male
      newborns were explored for cryptorchidism, hypospadias and micropenis. Cases were
      referred to the Pediatric Endocrine Clinic for endocrine and genetic
      investigations, and all parents were interviewed about their
      environmental/occupational exposure to EDCs before/during pregnancy by paediatric
      endocrinologists using a detailed questionnaire. We observed 56 cases of genital
      malformation (2.07%), including 23 cryptorchidism (0.85%), 15 hypospadias
      (0.55%), and 18 micropenis (0.66%). All cases exhibited normal/subnormal
      testosterone production and none presented androgen receptor or 5alpha-reductase
      gene mutation. More than 92% of these newborns presented foetal contamination by
      EDCs, as their mothers reported daily domestic use of pesticides (i.e., DDT) and
      other EDCs. Most of these undervirilized male newborns presented additional EDC
      contamination, as 80.36% of the mothers and 58.63% of the fathers reported paid
      or unpaid work that entailed the use of pesticides and other EDCs before/during
      pregnancy for the mothers and around the time of fertilization for the fathers.
      The high rate of micropenis in our population associated with an elevated
      percentage of parental environmental/occupational exposure to EDCs before/during
      pregnancy indicates that foetal contamination may be a risk factor for the
      development of male external genital malformation.

PMID- 22372606
TI  - Mesoporous thin-film on highly-sensitive resonant chemical sensor for relative
      humidity and CO2 detection.
AB  - Distributed sensing of gas-phase chemicals is a promising application for
      mesoporous materials when combined with highly sensitive miniaturized gas
      sensors. We present a direct application of a mesoporous silica thin film on a
      highly sensitive miniaturized resonant chemical sensor with a mass sensitivity at
      the zeptogram scale for relative humidity and CO(2) detection. Using mesoporous
      silica thin-film, we report one of the lowest volume resolutions and a sensitive
      detection of 5.1 * 10(-4)% RH/Hz to water vapor in N(2), which is 70 times higher
      than a device with a nontemplated silica layer. In addition, a mesoporous thin
      film that is functionalized with an amino-group is directly applied on the
      resonant sensor, which exhibits a volume sensitivity of 1.6 * 10(-4)%/Hz and a
      volume resolution of 1.82 * 10(-4)% to CO(2) in N(2).

PMID- 22372608
TI  - Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with
      cisplatin-based chemoresistance and shortened outcome in patients with stages III
      IV serous ovarian carcinoma.
AB  - AIMS: To correlate astrocyte elevated gene-1 (AEG-1) expression with the
      clinicopathological features and outcome of patients with stages III-IV ovarian
      serous carcinoma, and to clinically assess the involvement of AEG-1 in acquired
      cisplatin resistance. METHODS AND RESULTS: The frequency and intensity of
      immunohistochemical AEG-1 expression increased in a step-wise fashion from normal
      to chemosensitive to chemoresistant tissues. These observations were confirmed by
      Western blot analysis. AEG-1 expression level was correlated with lymph nodal
      metastasis, histological differentiation, residual tumour size and response to
      primary chemotherapy. Five-year progression-free survival (PFS) and overall
      survival (OS) rates were lower in the high-expression group than that in the low
      expression group. AEG-1 overexpression was an independent but poor prognostic
      factor in the OS and PFS of these patients, as determined by multivariate Cox
      regression analysis. Multivariate logistic regression analysis revealed that the
      presence of cisplatin-based chemoresistance was significantly associated with
      expression level of AEG-1 and the degree of residual disease (P = 0.0001 and P =
      0.0027, respectively). CONCLUSION: Our findings indicate that tumour AEG-1
      overexpression is associated with poor prognosis and cisplatin resistance in
      advanced serous ovarian cancer.

PMID- 22372609
TI  - MERGANSER: an empirical model to predict fish and loon mercury in New England
      lakes.
AB  - MERGANSER (MERcury Geo-spatial AssessmeNtS for the New England Region) is an
      empirical least-squares multiple regression model using mercury (Hg) deposition
      and readily obtainable lake and watershed features to predict fish (fillet) and
      common loon (blood) Hg in New England lakes. We modeled lakes larger than 8 ha
      (4404 lakes), using 3470 fish (12 species) and 253 loon Hg concentrations from
      420 lakes. MERGANSER predictor variables included Hg deposition, watershed
      alkalinity, percent wetlands, percent forest canopy, percent agriculture,
      drainage area, population density, mean annual air temperature, and watershed
      slope. The model returns fish or loon Hg for user-entered species and fish
      length. MERGANSER explained 63% of the variance in fish and loon Hg
      concentrations. MERGANSER predicted that 32-cm smallmouth bass had a median Hg
      concentration of 0.53 MUg g(-1) (root-mean-square error 0.27 MUg g(-1)) and
      exceeded EPA's recommended fish Hg criterion of 0.3 MUg g(-1) in 90% of New
      England lakes. Common loon had a median Hg concentration of 1.07 MUg g(-1) and
      was in the moderate or higher risk category of >1 MUg g(-1) Hg in 58% of New
      England lakes. MERGANSER can be applied to target fish advisories to specific
      unmonitored lakes, and for scenario evaluation, such as the effect of changes in
      Hg deposition, land use, or warmer climate on fish and loon mercury.

PMID- 22372610
TI  - Expedient enantioselective synthesis of cermizine D.
AB  - An efficient enantioselective synthesis of cermizine D has been developed that
      exploits the use of a common intermediate to access over 85% of the carbon
      backbone. Key steps include an organocatalyzed heteroatom Michael addition, a
      diastereoselective alkylation with alpha-iodomethyl phenyl sulfide, a conjugate
      addition to a vinyl sulfone species, and a sulfone coupling/desulfurization
      sequence to join the two major subunits.

PMID- 22372611
TI  - Three-dimensional packing structure and electronic properties of biaxially
      oriented poly(2,5-bis(3-alkylthiophene-2-yl)thieno[3,2-b]thiophene) films.
AB  - We use a systematic approach that combines experimental X-ray diffraction (XRD)
      and computational modeling based on molecular mechanics and two-dimensional XRD
      simulations to develop a detailed model of the molecular-scale packing structure
      of poly(2,5-bis (3-tetradecylthiophene-2-yl)thieno[3,2-b]thiophene) (PBTTT-C(14))
      films. Both uniaxially and biaxially aligned films are used in this comparison
      and lead to an improved understanding of the molecular-scale orientation and
      crystal structure. We then examine how individual polymer components (i.e.,
      conjugated backbone and alkyl side chains) contribute to the complete diffraction
      pattern, and how modest changes to a particular component orientation (e.g.,
      backbone or side-chain tilt) influence the diffraction pattern. The effects on
      the polymer crystal structure of varying the alkyl side-chain length from C(12)
      to C(14) and C(16) are also studied. The accurate determination of the three
      dimensional polymer structure allows us to examine the PBTTT electronic band
      structure and intermolecular electronic couplings (transfer integrals) as a
      function of alkyl side-chain length. This combination of theoretical and
      experimental techniques proves to be an important tool to help establish the
      relationship between the structural and electronic properties of polymer thin
      films.

PMID- 22372612
TI  - Skeletal indicators of pregnancy and parturition: a historical review.
AB  - Over a century of scientific literature has documented the research and analysis
      relating to the possible skeletal evidence of pregnancy, parturition, and
      childcare, yet today, there still exists variation in methodology and
      interpretation. Historical perspective facilitates understanding of the growth
      and development of the theories and research currently available to the forensic
      science community. Review of the relevant literature clearly indicates that
      specific skeletal alterations are not exclusively connected to obstetrical
      events. Although parturition and related events have been shown to leave various
      alterations on bone, the research record also demonstrates that other factors can
      contribute to the same or similar changes. Additionally, such alterations can
      often be found in nulliparous women and men and are frequently absent in parous
      and multiparous women. This literature review calls for the continued exploration
      of skeletal alterations for determining parity status in human skeletal remains.

PMID- 22372613
TI  - Immune reconstitution to cytomegalovirus following partially matched-related
      donor transplantation: impact of in vivo T-cell depletion and granulocyte colony
      stimulating factor-primed peripheral blood/bone marrow mixed grafts.
AB  - Cytomegalovirus (CMV) infection and delayed immune reconstitution remains a
      serious obstacle for successful partially matched-related donor transplantation
      (PMRD). We evaluated 42 patients for the development of CMV-specific CD8+ T
      lymphocytes (CTL(CMV) ) following granulocyte colony-stimulating factor-primed
      peripheral blood (PB) and bone marrow (BM) with anti-thymocyte globulin (ATG)
      based PMRD. PMRD recipients achieved a high frequency, proliferation capacity,
      and interferon-gamma response of CTL(CMV) at 1 year post transplantation.
      CTL(CMV) with the central memory CD45RO+CD62L+ cell phenotype expanded in PB and
      BM-resident CTL(CMV) displayed distinct phenotypes when CMV was reactivated.
      Although the incidence of CMV reactivation was high in PMRD patients (87.67%),
      only 11.90% of them developed CMV disease. In conclusion, after PMRD using mixed
      grafts with ATG-based conditioning, immune recovery to CMV seems to be early and
      fast, thereby reducing the incidence of CMV disease.

PMID- 22372614
TI  - Direct to consumer genetic testing: a systematic review of position statements,
      policies and recommendations.
AB  - In healthcare settings, genetic tests to determine whether an individual had
      inherited a genetic mutation are ordered by a health professional, and the
      results are interpreted and conveyed to the patient by that person. However,
      direct to consumer genetic testing (DTCGT) has enabled individuals to purchase
      genetic tests and receive results without the intervention of a health
      professional. To inform a set of guidelines for consumers and health
      professionals, we undertook a systematic review of position statements, policies
      and recommendations on the use of DTCGT. We performed a search of seven databases
      and the Internet for relevant documents. The search terms were 'direct to
      consumer' and 'genetic test', and documents in English published from 2002 to
      2011 were included. The search retrieved 314 items, of which 14 were eligible for
      review. Five themes were derived from thematic analysis: motivation for use,
      potential benefits, potential harms, recommendations to guide consumers and need
      for research. The authors of these documents described more potential harms than
      benefits, but, although some stated that direct to consumer testing should be
      actively discouraged, others supported consumer rights to make autonomous
      choices. Further research into the impact of direct to consumer testing on health
      services and consumers is required to inform policies.

PMID- 22372615
TI  - Total testosterone may not decline with ageing in Korean men aged 40 years or
      older.
AB  - OBJECTIVE: It is generally believed that gonadal function in men declines with
      ageing. However, observations on ageing-related decrease in total testosterone
      (TT) are not consistent. The aim of this study is to examine the ageing-related
      changes of testosterone and to investigate the influence of the ageing-related
      factors on TT. DESIGN: Changes of TT with ageing were observed in longitudinal
      design in a single health promotion centre. SUBJECTS: A total of 220 Korean men
      aged >=40 years were included between 2002 and 2011. TT assay was repeated for
      all subjects, with an interval of >=3 years. MEASUREMENTS: Information of medical
      history and lifestyle habits was collected. Anthropometry and blood pressure were
      measured. TT, glucose, creatinine, highly sensitive C-reactive protein, liver
      enzymes and lipid profiles were tested. RESULTS: Mean TT level did not decline
      significantly with ageing during median 4.3 years follow-up (18.1 vs 17.8 nm, P =
      0.439). Longitudinal change of TT was approximately + 0.8% per year. TT was
      negatively correlated with body mass index (BMI), waist circumference and
      glucose. With mixed effects model, diabetes (P = 0.038) and BMI (P = 0.007)
      affected TT level, but age and follow-up interval did not. CONCLUSIONS: TT did
      not change significantly in 220 Korean men for a median 4.3 years follow-up. TT
      was not influenced by the age and follow-up interval. BMI and diabetes mellitus
      affected TT decline.

PMID- 22372616
TI  - Fragmentation processes of hydrogen-deficient peptide radicals in matrix-assisted
      laser desorption/ionization in-source decay mass spectrometry.
AB  - The mechanism of in-source decay (ISD) in matrix-assisted laser
      desorption/ionization (MALDI) has been described. The MALDI-ISD with an oxidizing
      matrix is initiated by hydrogen abstraction from peptides to matrix molecules,
      leading to hydrogen-deficient peptide radicals. Subsequently, the C(alpha)-C and
      C(alpha)-H bonds are cleaved, forming the a*/x fragment pair and [M-2H],
      respectively. Those reactions competitively occur during MALDI-ISD processes. Our
      results suggest that the C(alpha)-H bond cleavage to form [M-2H] was induced by
      collisions between hydrogen-deficient peptide radicals and matrix molecules in
      the MALDI plume. In contrast, the C(alpha)-C bond cleavages occur via a
      unimolecular dissociation process and independently of the collision rate in the
      MALDI plume. The formation mechanism of the a-, b-, and d-series fragments are
      also described. We report 2,5-bis(2-hydroxyethoxy)-7,7,8,8
      tetracyanoquinodimethane (bisHE-TCNQ), being known as an organic semiconductor
      and an electron acceptor, as a novel suitable matrix for the MALDI-ISD of
      peptides via hydrogen abstraction.

PMID- 22372617
TI  - The stationary distribution of a continuously varying strategy in a class
      structured population under mutation-selection-drift balance.
AB  - Many traits and/or strategies expressed by organisms are quantitative phenotypes.
      Because populations are of finite size and genomes are subject to mutations,
      these continuously varying phenotypes are under the joint pressure of mutation,
      natural selection and random genetic drift. This article derives the stationary
      distribution for such a phenotype under a mutation-selection-drift balance in a
      class-structured population allowing for demographically varying class sizes
      and/or changing environmental conditions. The salient feature of the stationary
      distribution is that it can be entirely characterized in terms of the average
      size of the gene pool and Hamilton's inclusive fitness effect. The exploration of
      the phenotypic space varies exponentially with the cumulative inclusive fitness
      effect over state space, which determines an adaptive landscape. The peaks of the
      landscapes are those phenotypes that are candidate evolutionary stable strategies
      and can be determined by standard phenotypic selection gradient methods (e.g.
      evolutionary game theory, kin selection theory, adaptive dynamics). The curvature
      of the stationary distribution provides a measure of the stability by convergence
      of candidate evolutionary stable strategies, and it is evaluated explicitly for
      two biological scenarios: first, a coordination game, which illustrates that, for
      a multipeaked adaptive landscape, stochastically stable strategies can be singled
      out by letting the size of the gene pool grow large; second, a sex-allocation
      game for diploids and haplo-diploids, which suggests that the equilibrium sex
      ratio follows a Beta distribution with parameters depending on the features of
      the genetic system.

PMID- 22372618
TI  - The role of the Snf1 kinase in the adaptive response of Saccharomyces cerevisiae
      to alkaline pH stress.
AB  - Alkaline pH stress invokes a potent and fast transcriptional response in
      Saccharomyces cerevisiae that includes many genes repressed by glucose. Certain
      mutants in the glucose-sensing and -response pathways, such as those lacking the
      Snf1 kinase, are sensitive to alkalinization. In the present study we show that
      the addition of glucose to the medium improves the growth of wild-type cells at
      high pH, fully abolishes the snf1 alkali-sensitive phenotype and attenuates high
      pH-induced Snf1 phosphorylation at Thr(210). Lack of Elm1, one of the three
      upstream Snf1 kinases (Tos3, Elm1 and Sak1), markedly increases alkali
      sensitivity, whereas the phenotype of the triple mutant tos3 elm1 sak1 is even
      more pronounced than that of snf1 cells and is poorly rescued by glucose
      supplementation. DNA microarray analysis reveals that about 75% of the genes
      induced in the short term by high pH are also induced by glucose scarcity. Snf1
      mediates, in full or in part, the activation of a significant subset (38%) of
      short-term alkali-induced genes, including those encoding high-affinity hexose
      transporters and phosphorylating enzymes. The induction of genes encoding enzymes
      involved in glycogen, but not trehalose, metabolism is largely dependent of the
      presence of Snf1. Therefore the function of Snf1 in adaptation to glucose
      scarcity appears crucial for alkaline pH tolerance. Incorporation of micromolar
      amounts of iron and copper to a glucose-supplemented medium resulted in an
      additive effect and allows near-normal growth at high pH, thus indicating that
      these three nutrients are key limiting factors for growth in an alkaline
      environment.

PMID- 22372619
TI  - In vitro spermatogenesis: the dawn of a new era in the study of male infertility.

PMID- 22372620
TI  - Epirubicin as part of a multi-agent chemotherapy protocol for canine lymphoma.
AB  - The aim of the study was to report the outcome of treatment of 97 dogs with
      lymphoma that received a multi-agent chemotherapy protocol containing epirubicin
      as the primary anthracycline. Seventy-five dogs received a 25-week protocol with
      no maintenance phase whilst 22 dogs received a maintenance phase. Complete
      response rate was 96% and time to first relapse (TTR) and overall survival (OS)
      time for all dogs were 216 and 342 days, respectively. Dogs with T-cell lymphoma
      and those classified as WHO substage b had significantly poorer OS times and TTR.
      The protocol was well tolerated with toxicity similar to doxorubicin-containing
      protocols. Epirubicin as part of a multi-agent protocol is safe and effective in
      the treatment of canine multicentric lymphoma. There is a high initial response
      rate and an overall median survival time that is similar to other published
      doxorubicin-containing protocols. 

PMID- 22372621
TI  - An assessment of the usefulness of routine histological examination in hanging
      deaths.
AB  - A retrospective study was carried out on 100 randomly selected medico-legal
      autopsies of victims who had committed suicide by hanging. All cases had
      undergone full police and coronial investigation. Complete external and internal
      examinations had been carried out including routine histological examination of
      organs. The age range of victims was 15-94 years (average, 41.7 years) with a
      male-to-female ratio of 7:1. External and internal injuries were consistent with
      the reported events. Diagnoses based purely on histology included hepatic
      steatosis (n = 16), asthma (n = 3), lymphocytic thyroiditis (n = 2), and
      pulmonary and cardiac sarcoidosis (n = 1). A large cell carcinoma of the lung and
      a rectal adenocarcinoma were confirmed. Histological evaluation was, however, of
      limited usefulness in contributing to the medico-legal evaluation of cases, with
      careful scene, external and internal examinations providing the most relevant
      information. The results of histological examination of tissues were all
      incidental to the cause, mechanism, and manner of death.

PMID- 22372622
TI  - Validating and understanding ring conformations using small molecule
      crystallographic data.
AB  - Understanding the conformational preferences of ring structures is fundamental to
      structure-based drug design. Although the Cambridge Structural Database (CSD)
      provides information on the preferred conformations of small molecules, analyzing
      this data can be very time-consuming. In order to overcome this hurdle, tools
      have been developed for quickly extracting geometrical preferences from the CSD.
      Here we describe how the program Mogul has been extended to analyze and compare
      ring conformations, using a library derived from over 900 000 ring fragments in
      the CSD. We illustrate how these can be used to understand the conformational
      preferences of molecules in a crystal lattice and bound to proteins.

PMID- 22372623
TI  - Automatic detection of age-related macular degeneration pathologies in retinal
      fundus images.
AB  - Advanced techniques in image processing and analysis are being extensively
      studied to assist clinical diagnoses. Digital colour retinal fundus images are
      widely utilised to investigate various eye diseases. In this paper, we describe
      the detection of optic disc (OD), macula and age-related macular degeneration
      (ARMD) pathologies of the macular regions in colour fundus images. ARMD causes
      the loss of central vision in older adults. If the disease is detected early and
      treated promptly, much of the vision loss can be prevented. Eighty colour retinal
      fundus images were tested using our proposed algorithm. The Hough transform was
      employed for OD determination. A fundus coordinate system was established based
      on the macula location. An ARMD pathology detection methodology using a
      subtraction process after contrast-limited adaptive histogram equalisation
      operations was proposed. The accuracies of the automated segmentations of the OD,
      macula and ARMD pathologies obtained were 100%, 100% and 95.49%, respectively.
      These results show that our algorithm is a useful tool for detecting ARMD in
      retinal fundus images. The application of our method may reduce the time needed
      by ophthalmologists to diagnose ARMD pathology while providing dependable
      detection precision. Integration of our technique into traditional software could
      be used in clinical implementations as an aid in disease diagnosis and as a tool
      for quantitative evaluation of treatment effectiveness.

PMID- 22372624
TI  - Managing frostbite in a South African patient.
AB  - This report focuses on a 23-year-old man of African-Caribbean origin who
      presented to a Burns unit with soft-tissue loss following a road traffic
      collision (RTC) in an extremely cold weather. Having been involved in the RTC, he
      walked from the scene to the hospital subsequently sustaining frostbite to both
      his feet. This case illustrates the management of frostbite and highlights some
      key principles in the management of this problem. 

PMID- 22372625
TI  - Biomimetic total synthesis of (-)-isatisine A.
AB  - The biomimetic total synthesis of (-)-isatisine A, a novel alkaloid with an
      unprecedented fused tetracyclic skeleton, was accomplished in 8 steps from indole
      and 4,6-O-isopropylidene-protected glucal. The synthesis features a convergent
      synthetic strategy which relies on nucleophilic addition and a biomimetic
      benzilic ester rearrangement as key reactions.

PMID- 22372626
TI  - Effects of changing jaw height on F1 during babble: a case study at 9 months.
AB  - An empirical gap exists in our understanding of the extent that mandibular
      kinematics modulate acoustic changes in natural babble productions of infants.
      Data were recorded from a normal developing 9-month-old infant. Mandibular
      position was tracked from the infant during vowel and canonical babble. Linear
      predictive coding analysis was used to track estimates of formant center
      frequency for F1. For each sample, a correlation coefficient was computed between
      changes in jaw height and formant history for F1. A Mann-Whitney rank sum test
      reached significance for differences among coefficients for vowel and canonical
      babble. Coefficients for vowel babble productions were nearest to -1 with a
      median of r=-0.76, showing the strongest relationship between jaw position and
      formant history, while the median for canonical babble coefficients was r=-0.54,
      indicating greater contribution of the tongue and lips. This 9-month-old infant
      exhibited plasticity for coordinating the jaw, tongue and lips among babble
      types.

PMID- 22372627
TI  - On the ictogenic properties of the piriform cortex in vitro.
AB  - PURPOSE: The piriform cortex (PC) is known to be epileptic-prone and it may be
      involved in the manifestation of limbic seizures. Herein, we have characterized
      some electrophysiologic and pharmacologic properties of the spontaneous
      epileptiform activity generated by PC networks maintained in vitro. METHODS: We
      performed field potential recordings from the PC in coronal or sagittal rat brain
      slices along with pharmacologic manipulations of gamma-aminobutyric acid
      (GABA)ergic and glutamatergic signaling during application of the convulsant drug
      4-aminopyridine (4AP, 50 MUm). KEY FINDINGS: Coronal and sagittal preparations
      generated interictal-like and ictal-like epileptiform discharges with similar
      duration and frequency. Ictal-like discharges in sagittal slices were initiated
      mostly in the PC anterior subregion, whereas interictal activity did not have any
      preferential site of origin. In sagittal slices, high frequency oscillations
      (HFOs) at 80-200 Hz were detected mainly at the beginning of the ictal discharge
      in both posterior and anterior subregions. N-Methyl-d-aspartate (NMDA) receptor
      antagonism abolished ictal discharges, but failed to influence interictal
      activity. In the absence of ionotropic glutamatergic transmission, PC networks
      generated slow, GABA receptor-dependent events. Finally, GABA(A) receptor
      antagonism during application of 4AP only, abolished ictal discharges and
      disclosed recurrent interictal activity. SIGNIFICANCE: Our findings demonstrate
      that PC networks can sustain in vitro epileptiform activity induced by 4AP. HFOs,
      which emerge at the onset of ictal activity, may be involved in PC ictogenesis.
      As reported in several cortical structures, ionotropic glutamatergic
      neurotransmission is necessary but not sufficient for ictal discharge generation,
      a process that also requires operative GABA(A) receptor-mediated signaling.

PMID- 22372628
TI  - Long-term safety and efficacy in patients with uncontrolled partial-onset
      seizures treated with adjunctive lacosamide: results from a Phase III open-label
      extension trial.
AB  - PURPOSE: To evaluate the long-term (up to 5 years exposure) safety and efficacy
      of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset
      seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label
      extension trial SP756 (NCT00522275). METHODS: Patients who completed the double
      blind trial SP754 (NCT00136019) were eligible to participate in this open-label
      extension trial (SP756). At the conclusion of trial SP754, patients had
      transitioned to lacosamide 200 mg/day. Subsequent dosage adjustments of
      lacosamide (100-800 mg/day) and/or concomitant AEDs were allowed to optimize
      tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs),
      vital signs, body weight, clinical laboratory data, electrocardiography studies,
      and seizure frequency were evaluated. KEY FINDINGS: A total of 308 patients
      received open-label lacosamide and 138 patients (44.8%) completed the long-term
      trial. The median modal dose (defined as the daily lacosamide dose a patient
      received for the longest duration during the treatment period) was 500 mg/day.
      The percentages of patients with lacosamide exposure >1, >2, >3, or >4 years were
      75%, 63%, 54%, and 29%, respectively. Primary reasons for discontinuation were
      lack of efficacy (26%) and adverse events (11%). Common TEAEs (>=15%) were
      dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall,
      vomiting, and diplopia. TEAEs that led to discontinuation in >=1.0% of patients
      were dizziness (1.6%) and convulsion (1.0%). The median percent reductions from
      baseline of trial SP754 in 28-day seizure frequency were 53.4%, 55.2%, 58.1%, and
      62.5%, respectively, for 1-, 2-, 3-, and 4-year completers. The >=50% responder
      rates were 52.8%, 56.5%, 58.7%, and 62.5% for 1-, 2-, 3-, and 4-year completers,
      respectively. Seven of eight patients on lacosamide monotherapy for >=12 months
      were deemed 50% responders. Of patients exposed to lacosamide >=2 years, 3.1%
      remained seizure-free for a period >=2 years. SIGNIFICANCE: Long-term (up to 5
      years) lacosamide treatment was generally well tolerated. The safety profile of
      lacosamide observed in this trial is consistent with that established in previous
      double-blind, placebo-controlled trials. Although the open-label trial design
      limits the analysis of efficacy, long-term reduction in seizure frequency and
      maintenance of efficacy was observed.

PMID- 22372629
TI  - Evaluation of the permeability and P-glycoprotein efflux of carbamazepine and
      several derivatives across mouse small intestine by the Ussing chamber technique.
AB  - PURPOSE: The rational discovery and development of new antiepileptic drugs (AEDs)
      with safer therapeutic index and better pharmacokinetic properties is still
      warranted nowadays. Because the long-term management of epilepsy is attained by
      means of orally administered AEDs, investigation of their potential to be well
      absorbed at the intestinal level is mandatory. Moreover, involvement of the
      efflux transport mediated by P-glycoprotein (P-gp) may compromise the systemic
      and central nervous system disposition of AEDs. Therefore, this study aimed at
      characterizing mouse jejunal passive transport and the possible active efflux
      mediated by P-gp of a series of dibenz[b,f]azepine-5-carboxamide derivatives
      (carbamazepine [CBZ], oxcarbazepine [OXC], S-licarbazepine [S-Lic], R
      licarbazepine [R-Lic], carbamazepine-10,11-epoxide [CBZ-E], 10,11-trans-dihydroxy
      10,11-dihydro-carbamazepine [trans-diol], and BIA 2-024), which comprise some
      AEDs and metabolites. METHODS: Permeation studies were performed with freshly
      excised mouse jejunum segments mounted in Ussing chambers. Absorptive (M-S) and
      secretive (S-M) transports were analyzed with and without verapamil, which is a P
      gp inhibitor widely recognized. Apparent permeability coefficients (P(app) ) in
      both directions and in absence or presence of verapamil were determined for each
      test compound. The in vitro method was validated using five controls that
      included high and low permeable markers with known absorption fraction (Fa) and
      also well-known P-gp substrates. The integrity of intestinal membrane was
      guaranteed during the assay by measuring the transepithelial electrical
      resistance. KEY FINDINGS: The correlation obtained between P(app) (M-S) and Fa of
      references was high (r(2) = 0.9945), and could be used to classify the
      derivatives according to Biopharmaceutical Classification System: CBZ and OXC
      were the only classified as highly permeable. The P(app) (S-M) of OXC, CBZ-E, R
      Lic, and BIA 2-024 were significantly higher than their P(app) (M-S). After
      verapamil addition, their P(app) (S-M) lowered while P(app) (S-M) increased,
      suggesting the involvement of P-gp on the transport of those compounds across
      mouse jejunum segments. In opposition, CBZ, S-Lic, and trans-diol presented no
      statistical differences between the P(app) values reported in both directions,
      with or without verapamil. The results reported herein suggest that differences
      in biodisposition of S-Lic and R-Lic might result from their distinct interaction
      with P-gp. SIGNIFICANCE: The Ussing chamber model used herein showed to be useful
      for predicting Fa of AEDs and the involvement of efflux transport, namely P-gp,
      on their absorption. This is an important achievement as compounds that are not
      transported by P-gp may offer advantages when used in patients with
      pharmacoresistant epilepsy.

PMID- 22372630
TI  - Cliniconeuropathologic correlations show astroglial albumin storage as a common
      factor in epileptogenic vascular lesions.
AB  - PURPOSE: Intracerebral vascular malformations including cavernous angiomas (CAs)
      and arteriovenous malformations (AVMs) are an important cause of chronic
      pharmacoresistant epilepsies. Little is known about the pathogenetic basis of
      epilepsy in patients with vascular malformations. Intracerebral deposits of iron
      containing blood products have been generally regarded as responsible for the
      strong epileptogenic potential of CAs. Here, we have analyzed whether blood-brain
      barrier (BBB) dysfunction and subsequent astrocytic albumin uptake, recently
      described as critical trigger of focal epilepsy, represent pathogenetic factors
      in vascular lesion-associated epileptogenesis. METHODS: We examined the
      correlation between hemosiderin deposits, albumin accumulation, and several
      clinical characteristics in a series of 80 drug-refractory epilepsy patients with
      CAs or AVMs who underwent surgical resection. Analysis of clinical parameters
      included gender, age of seizure onset, epilepsy frequency, duration of epilepsy
      before surgery, and postoperative seizure outcome classification according to
      Engel class scale. Hemosiderin deposits in the adjacent brain tissue of the
      vascular lesion were semiquantitatively analyzed. Fluorescent double
      immunohistochemistry using GFAP/albumin costaining was performed to study albumin
      extravasation. KEY FINDINGS: Our results suggest that a shorter duration of
      preoperative epilepsy is correlated with significantly better postsurgical
      outcome (p < 0.05), whereas no additional clinical or neuropathologic parameter
      correlated significantly with the postsurgical seizure situation. Intriguingly,
      we observed strong albumin immunoreactivity within the vascular lesion and in
      perilesional astrocytes (57.65 +/- 4.05%), but not in different control groups.
      SIGNIFICANCE: Our present data on albumin uptake in brain tissue adjacent to AVMs
      and CAs suggests BBB dysfunction and accumulation of albumin within astrocytes as
      a new pathologic feature potentially associated with the epileptogenic mechanism
      for vascular lesions and provides novel therapy perspectives for
      antiepileptogenesis in affected patients.

PMID- 22372631
TI  - Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new
      treatment options for chordomas? A retrospective clinical and immunohistochemical
      study.
AB  - AIMS: The overall prognosis of chordoma is poor, and current treatment options
      are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is
      important for cell signalling, and attractive for selective inhibition. We
      investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a
      series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a
      potential target for specific inhibition in chordomas. METHODS AND RESULTS: Fifty
      chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated
      immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight
      chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed
      IGF-2. Semi-quantitative analyses revealed a moderate to strong staining
      intensity in >= 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32
      (64%) and eight (16%) chordomas, respectively. Tumour volume correlated
      significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042).
      CONCLUSIONS: IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1
      expression is much stronger than IGF-2 expression. Patients whose chordomas show
      a moderate to strong staining intensity in >= 50% of tumour cells for IGF-1R
      (36%) might benefit most from IGF-1R targeting, particularly if they suffer from
      large and surgically non-resectable chordomas.

PMID- 22372632
TI  - Monitoring fluid balance in the neonate.

PMID- 22372633
TI  - HDAC6 at the Intersection of Neuroprotection and Neurodegeneration.
AB  - Histone deacetylase 6 (HDAC6) catalyzes multiple reactions. We summarize the
      current knowledge on HDAC6, its targets and functions. Among others, HDAC6
      recognizes damaged proteins and assures that these proteins are destroyed by
      autophagy. On the other hand, HDAC6 also modifies the tracks used by the
      clearance mechanism so that axonal transport becomes less efficient. We
      hypothesize that a disturbance in the equilibrium between the different functions
      of HDAC6 could play an important role in neurodegeneration.

PMID- 22372634
TI  - Fluorous oxime palladacycle: a precatalyst for carbon-carbon coupling reactions
      in aqueous and organic medium.
AB  - To facilitate precatalyst recovery and reuse, we have developed a fluorous, oxime
      based palladacycle 1 and demonstrated that it is a very efficient and versatile
      precatalyst for a wide range of carbon-carbon bond formation reactions (Suzuki
      Miyaura, Sonogashira, Stille, Heck, Glaser-type, and Kumada) in either aqueous or
      organic medium under microwave irradiation. Palladacycle 1 could be recovered
      through F-SPE in various coupling reactions with recovery ranging from 84 to 95%
      for the first cycle. Inductively coupled plasma optical emission spectrometry
      (ICP-OES) analyses of the Pd content in the crude product from each class of
      transformation indicated extremely low levels of leaching and the palladacycle
      could be reused four to five times without significant loss of activity.

PMID- 22372635
TI  - Aerobic soil biodegradation of 8:2 fluorotelomer stearate monoester.
AB  - A laboratory investigation on the biotransformation of 8:2 fluorotelomer stearate
      monoester (8:2 FTS) in aerobic soils was conducted by monitoring the loss of 8:2
      FTS, production of 8:2 fluorotelomer alcohol (8:2 FTOH) and stearic acid, which
      would be released by cleavage of the ester linkage, and subsequent degradation
      products from FTOH for 80 d. Soil microcosms were extracted with ethyl acetate
      followed by two heated 90/10 v/v acetonitrile/200 mM NaOH extractions. 8:2 FTS
      was degraded with an observed half-life (t(1/2)) of 10.3 d. The rate of 8:2 FTS
      biotransformation substantially decreased after 20 d with 22% of 8:2 FTS still
      remaining on day 80. No biotransformation of 8:2 FTS occurred in autoclaved soil
      controls, which remained sterile with 102 +/- 6% recovery, through day 20. 8:2
      FTOH was generated with cleavage of the ester linkage of 8:2 FTS followed by a
      rapid decline (t(1/2) ~ 2 d) due to subsequent biodegradation. All the expected
      8:2 FTOH degradation products were detected including 8:2 fluorotelomer
      unsaturated and saturated carboxylic acids, 7:2s FTOH, 7:3 acid, and three
      perfluoroalkyl carboxylic acids with the most prominent being perfluorooctanoic
      acid (PFOA). PFOA consistently increased over time reaching 1.7 +/- 0.07 mol % by
      day 80. Although cleavage of the ester linkage was evidenced by 8:2 FTOH
      production, an associated trend in stearic acid concentrations was not clear
      because of complex fatty acid metabolism dynamics in soil. Further analysis of
      mass spectrometry fragmentation patterns and chromatography supported the
      conclusion that hydrolysis of the ester linkage is predominantly the first step
      in the degradation of 8:2 FTS with the ultimate formation of terminal products
      such as PFOA.

PMID- 22372636
TI  - Mixtures of endocrine disrupting contaminants modelled on human high end
      exposures: an exploratory study in rats.
AB  - By diminishing the action of androgens during gestation, certain chemicals can
      induce irreversible demasculinization and malformations of sex organs in the male
      rat after gestational exposure. Studies with mixtures of such anti-androgens have
      shown that substantial combined effects occur even though each individual
      chemical is present at low, ineffective doses, but the effects of mixtures
      modelled based on human intakes have not previously been investigated. To address
      this issue for the first time, we selected 13 chemicals for a developmental
      mixture toxicity study in rats where data about in vivo endocrine disrupting
      effects and information about human exposures was available, including
      phthalates, pesticides, UV-filters, bisphenol A, parabens and the drug
      paracetamol. The mixture ratio was chosen to reflect high end human intakes. To
      make decisions about the dose levels for studies in the rat, we employed the
      point of departure index (PODI) approach, which sums up ratios between estimated
      exposure levels and no-observed-adverse-effect-level (NOAEL) values of individual
      substances. For high end human exposures to the 13 selected chemicals, we
      calculated a PODI of 0.016. As only a PODI exceeding 1 is expected to lead to
      effects in the rat, a total dose more than 62 times higher than human exposures
      should lead to responses. Considering the high uncertainty of this estimate,
      experience on lowest-observed-adverse-effect-level (LOAEL)/NOAEL ratios and
      statistical power of rat studies, we expected that combined doses 150 times
      higher than high end human intake estimates should give no, or only borderline
      effects, whereas doses 450 times higher should produce significant responses.
      Experiments indeed showed clear developmental toxicity of the 450-fold dose in
      terms of increased nipple retention (NR) and reduced ventral prostate weight. The
      150-fold dose group exhibited significantly increased NR. These observations
      suggest that highly exposed population groups, especially women of reproductive
      age, may not be protected sufficiently against the combined effects of chemicals
      that affect the hormonal milieu required for normal male sexual differentiation.

PMID- 22372638
TI  - Biomarkers and transcriptome profiling of lung cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. High
      throughput technologies such as microarrays provide an opportunity to explore
      biomarkers for cancer prevention, prognosis and treatment guidance. Recent
      studies have revealed many biomarkers with the potential for clinical
      application. However, major limitations still exist. Although useful data on
      cancer genomics has accumulated rapidly, there has also been a simultaneous
      tendency for amplification of the complex relationships among the enormous number
      of variables that need to be considered. Disentangling these complex gene-gene
      interactions requires new approaches to data analysis to reveal information that
      has been obscured by traditional methods. Here, we review the current findings on
      biomarker identification in lung cancer, address their limitations and discuss
      some future directions for improvements in this area of research.

PMID- 22372637
TI  - The enteropathogenic E. coli effector EspH promotes actin pedestal formation and
      elongation via WASP-interacting protein (WIP).
AB  - Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) are
      diarrheagenic pathogens that colonize the gut mucosa via attaching-and-effacing
      lesion formation. EPEC and EHEC utilize a type III secretion system (T3SS) to
      translocate effector proteins that subvert host cell signalling to sustain
      colonization and multiplication. EspH, a T3SS effector that modulates actin
      dynamics, was implicated in the elongation of the EHEC actin pedestals. In this
      study we found that EspH is necessary for both efficient pedestal formation and
      pedestal elongation during EPEC infection. We report that EspH induces actin
      polymerization at the bacterial attachment sites independently of the Tir
      tyrosine residues Y474 and Y454, which are implicated in binding Nck and
      IRSp53/ITRKS respectively. Moreover, EspH promotes recruitment of neural Wiskott
      Aldrich syndrome protein (N-WASP) and the Arp2/3 complex to the bacterial
      attachment site, in a mechanism involving the C-terminus of Tir and the WH1
      domain of N-WASP. Dominant negative of WASP-interacting protein (WIP), which
      binds the N-WASP WH1 domain, diminished EspH-mediated actin polymerization. This
      study implicates WIP in EPEC-mediated actin polymerization and pedestal
      elongation and represents the first instance whereby N-WASP is efficiently
      recruited to the EPEC attachment sites independently of the Tir:Nck and
      Tir:IRTKS/IRSp53 pathways. Our study reveals the intricacies of Tir and EspH
      mediated actin signalling pathways that comprise of distinct, convergent and
      synergistic signalling cascades.

PMID- 22372639
TI  - Synthetically simple, highly resilient hydrogels.
AB  - Highly resilient synthetic hydrogels were synthesized by using the efficient
      thiol-norbornene chemistry to cross-link hydrophilic poly(ethylene glycol) (PEG)
      and hydrophobic polydimethylsiloxane (PDMS) polymer chains. The swelling and
      mechanical properties of the hydrogels were controlled by the relative amounts of
      PEG and PDMS. The fracture toughness (G(c)) was increased to 80 J/m(2) as the
      water content of the hydrogel decreased from 95% to 82%. In addition, the
      mechanical energy storage efficiency (resilience) was more than 97% at strains up
      to 300%. This is comparable with one of the most resilient materials known:
      natural resilin, an elastic protein found in many insects, such as in the tendons
      of fleas and the wings of dragonflies. The high resilience of these hydrogels can
      be attributed to the well-defined network structure provided by the versatile
      chemistry, low cross-link density, and lack of secondary structure in the polymer
      chains.

PMID- 22372640
TI  - Effects of surgical implants on high-field magnetic resonance images of the
      normal canine stifle.
AB  - To determine the effect of surgical implants on the depiction of canine stifle
      anatomy in magnetic resonance (MR) images, three canine cadaver limbs were imaged
      at 1.5 T before and after tibial plateau leveling osteotomy (TPLO), tibial
      tuberosity advancement (TTA), and extra-capsular stabilization (ECS),
      respectively. Susceptibility artifacts associated with implants were identified
      in MR images as a signal void and/or signal misregistration, which obscured or
      distorted the anatomy. Using the preoperative images as a reference, articular
      structures of the stifle in postoperative images were graded using an ordinal
      scale to describe to what degree each anatomic structure could be evaluated for
      clinical purposes. The TPLO implant, which contains ferromagnetic stainless
      steel, produced marked susceptibility artifacts that obscured or distorted most
      stifle anatomy. The titanium alloy TTA implants and the stainless steel crimps
      used for ECS produced susceptibility artifacts that mainly affected the lateral
      aspect of the stifle, but allowed the cruciate ligaments and medial meniscus to
      be evaluated satisfactorily. Susceptibility artifact was significantly less
      marked in images obtained using turbo spin-echo (TSE) sequences than in sequences
      employing spectral fat saturation. Clinical MR imaging of canine stifles
      containing certain metallic implants is feasible using TSE sequences without fat
      saturation.

PMID- 22372641
TI  - Cortisol response to synacthen stimulation is attenuated following abusive head
      trauma.
AB  - BACKGROUND: Child abuse and other early-life environmental stressors are known to
      affect the hypothalamic-pituitary-adrenal axis. We sought to compare synacthen
      stimulated cortisol responses in children who suffered inflicted or accidental
      traumatic brain injury (TBI). METHODS: Children with a history of early-childhood
      TBI were recruited from the Starship Children's Hospital database (Auckland, New
      Zealand, 1992-2010). All underwent a low-dose ACTH(1-24)  (synacthen 1 MUg IV)
      test, and serum cortisol response was compared between inflicted (TBI(I) ) and
      accidental (TBI(A) ) groups. RESULTS: We assessed 64 children with TBI(I)  and
      134 with TBI(A) . Boys were more likely than girls to suffer accidental (P <
      0.001), but not inflicted TBI. TBI(I)  children displayed a 14% reduction in peak
      stimulated cortisol in comparison with the TBI(A)  group (P < 0.001), as well as
      reduced cortisol responses at + 30 (P < 0.01) and + 60 min (P < 0.001).
      Importantly, these differences were not associated with severity of injury. The
      odds ratio of TBI(I)  children having a mother who suffered domestic violence
      during pregnancy was 6.2 times that of the TBI(A)  group (P < 0.001). However,
      reported domestic violence during pregnancy or placement of child in foster care
      did not appear to affect cortisol responses. CONCLUSION: Synacthen-stimulated
      cortisol response is attenuated following inflicted TBI in early childhood. This
      may reflect chronic exposure to environmental stress as opposed to pituitary
      injury or early-life programming.

PMID- 22372642
TI  - The effect of second trimester emergency cervical cerclage on perinatal outcome.
AB  - OBJECTIVE: To evaluate the effectiveness of emergency cervical cerclage and to
      determine predictors of failure or success in women with cervical incompetence.
      METHODS: Medical records were reviewed for clinical and demographic data,
      gestational age at time of cerclage, cerclage-delivery interval, gestational age
      at time of delivery; and birth weight. Predictors of success and failure were
      analyzed. RESULT: Forty-three pregnant women between 18 and 25 weeks of gestation
      were recruited. The mean gestational age at time of cerclage was 21 weeks. The
      mean cerclage-delivery interval was 64 days. The mean gestation at delivery was
      31 weeks and the mean neonatal birth weight was 2166 g. Whether cerclage done
      before or after 20 weeks, the difference in cerclage-delivery interval was
      insignificant while the difference in gestational age at time of delivery and
      neonatal birth weight was significant. Presence of infection, presence of
      symptoms, membranes through the cervix and dilated cervix >3 cm are frequently
      associated with failure. CONCLUSION: Emergency cervical cerclage is effective in
      prolonging pregnancy and improving neonatal outcome in patient with cervical
      incompetence. However, large prospective randomized controlled studies are
      recommended.

PMID- 22372644
TI  - Moving forward in ocular pharmacology.

PMID- 22372643
TI  - Dual peptide nucleic acid- and peptide-functionalized shell cross-linked
      nanoparticles designed to target mRNA toward the diagnosis and treatment of acute
      lung injury.
AB  - In this work, multifunctional biosynthetic hybrid nanostructures were prepared
      and studied for their potential utility in the recognition and inhibition of mRNA
      sequences for inducible nitric oxide synthase (iNOS), which are overexpressed at
      sites of inflammation, such as in cases of acute lung injury. Shell cross-linked
      knedel-like polymer nanoparticles (SCKs) that present peptide nucleic acids, for
      binding to complementary mRNAs, and cell penetrating peptides (CPPs), to gain
      cell entry, along with fluorescent labels and sites for radiolabeling, were
      prepared by a series of robust, efficient, and versatile synthetic steps that
      proceeded from monomers to polymers to functional nanoparticles. Amphiphilic
      block graft copolymers having combinations of methoxy- and thioacetyl-terminated
      poly(ethylene glycol) (PEG) and DOTA-lysine units grafted from the backbone of
      poly(acrylic acid) (PAA) and extending with a backbone segment of poly(octadecyl
      acrylate-co-decyl acrylate) (P(ODA-co-DA)) were prepared by a combination of
      reversible addition-fragmentation chain transfer (RAFT) polymerization and
      chemical modification reactions, which were then used as the building blocks for
      the formation of well-defined SCKs decorated with reactive thiols accessible to
      the surface. Fluorescent labeling with Alexa Fluor 633 hydrazide was then
      accomplished by amidation with residual acrylic acid residues within the SCK
      shells. Finally, the PNAs and CPP units were covalently conjugated to the SCKs
      via Michael addition of thiols on the SCKs to maleimide units on the termini of
      PNAs and CPPs. Confirmation of the ability of the PNAs to bind selectively to the
      target iNOS mRNAs when tethered to the SCK nanoparticles was determined by in
      vitro competition experiments. When attached to the SCKs having a hydrodynamic
      diameter of 60 +/- 16 nm, the K(d) values of the PNAs were ca. an order of
      magnitude greater than the free PNAs, while the mismatched PNA showed no
      significant binding.

PMID- 22372645
TI  - Empirical protein partition functions.
AB  - In the present paper, we outline how to construct the partition function for a
      protein using empirical heat capacity data. The procedure is based on the
      calculation of a set of energy moments from the temperature dependence of the
      heat capacity. Given a set of energy moments, one can then use the maximum
      entropy method to calculate an approximate energy distribution for the protein;
      the more energy moments one has, the better the approximation. The energy
      distribution can then be used to calculate the probability that the molecule is
      in a given energy level, which, using standard statistical mechanics, gives the
      degeneracy of the particular energy level. The degeneracy as a function of energy
      is the central ingredient in the construction of the partition function. Given
      the partition function, one can calculate all of the thermodynamic functions of
      the protein (free energy, energy, entropy, heat capacity, and energy probability
      distribution) as a function of temperature. The three-dimensional plot of the
      probability that the protein has a given energy at a given temperature tells one
      graphically (without imposing the assumption) whether or not it is a good
      approximation to divide the terms in the partition function into two or more
      groups, reflecting, for example, the presence of distinct native and denatured
      species.

PMID- 22372646
TI  - Ecstasy and suicide.
AB  - Deaths due to the ring-derivative amphetamines are not common and are usually
      accidental involving dehydration and hyperthermia. Suicides from 3,4
      methylenedioxymethamphetamine (MDMA) and related ring-derivative amphetamines
      overdose are rare. A 15-year-old female who had a history of depression and
      previous suicide attempts was found dead with a suicide note. Toxicology
      demonstrated lethal serum concentrations of MDMA (9.3 mg/L), with 34 mg/kg of
      MDMA in the liver, 2.4 mg/L in the urine, and 530 mg/kg in the stomach. The cause
      of death was MDMA toxicity, the manner suicide. While MDMA may be detected in
      victims in other drug-related or traumatic deaths, it is only rarely used in
      isolation in suicide, with a predominance in the 21- to 25-year-old range.
      Despite the rarity of such events, the possibility of a nonaccidental manner of
      death should be considered when high levels of MDMA and associated amphetamines
      are found at autopsy.

PMID- 22372647
TI  - Endoperoxide synthesis by photocatalytic aerobic [2 + 2 + 2] cycloadditions.
AB  - Structurally novel endoperoxides can be sythesized by the photocatalytic
      cyclotrimerization of bis(styrene) substrates with molecular oxygen. The optimal
      catalyst for this process is Ru(bpz)(3)(2+), which is a markedly more efficient
      catalyst for these photooxygention reactions than conventional organic
      photosensitizers. The 1,2-dioxolane products are amenable to synthetic
      manipulation and can be easily processed to 1,4-diols and gamma-hydroxyketones.
      An initial screen of the biological activity of these compounds reveals promising
      inhibition of cancer cell growth.

PMID- 22372648
TI  - Chronic lymphocytic leukaemia in the cat: 18 cases (2000-2010).
AB  - There is little information regarding the presentation, biologic behaviour,
      treatment and prognosis in cats with chronic lymphocytic leukaemia (CLL), and
      further investigation is needed to characterize this disease in cats. The goal of
      this study was to describe the clinical presentation, response to treatment and
      prognosis of feline CLL. A multi-institutional retrospective study of 18 cats
      diagnosed with CLL between 2000 and 2010 was performed. CLL was defined as the
      presence of a mature lymphocytosis (>9000 lymphocytes uL(-1) ) and confirmation
      of an immunophenotypically monomorphic or clonal lymphoid population. Each
      patient was required to also have at least one of the two following criteria: (1)
      concurrent cytopenia of at least one cell line and/or (2) >15% mature lymphocytes
      in the bone marrow. Data on signalment, history, clinical signs,
      clinicopathologic features and response to treatment were reviewed. Median age of
      the cats at initial presentation was 12.5 years (range: 5-20 years). The most
      common presenting complaint was chronic weight loss, which was present in 8/18
      (44%) cats. Sixteen of 18 (89%) cats were treated with chlorambucil and
      prednisolone; four of these cats also received vincristine. Two (11%) cats were
      treated with multi-agent injectable chemotherapy (L-CHOP, l-asparaginase,
      cyclophosphamide, doxorubicin, vincristine, prednisolone). Eighty-eight percent
      of cats evaluable for response achieved a complete (nine cats) or partial (six
      cats) remission. Median overall remission was 15.7 months (range: 1.3-22.8
      months). The median overall survival in the 17 cats with follow-up data was 14.4
      months (range: 0.9-25.3 months). Results of this study suggest that CLL affects
      older-aged cats and responds favourably to treatment with oral chlorambucil and
      prednisolone. 

PMID- 22372649
TI  - Playing dominoes with sexual medicine.

PMID- 22372651
TI  - Cardiometabolic risk and female sexual health: the Princeton III summary.
AB  - INTRODUCTION: Female sexual function is dependent, in part, upon normal
      endothelial function within the genital arterial (hypogastric-cavernosal)
      vascular bed. The first two Princeton Consensus Conferences were focused on
      relationships between male sexual function and cardiovascular health, and
      development of contemporary clinical guidelines for dysfunction management. AIM:
      The third Princeton Consensus Conference updated recommendations and assessed,
      for the first time, the association between female sexual dysfunction (FSD) and
      presence of systemic vascular endothelial dysfunction and its consequences in
      women. This report focuses on the association between cardiometabolic risk
      factors and female sexual health. METHODS: A panel of experts reviewed
      multinational data concerning associations between several cardiometabolic risks
      in women (hypertension, dyslipidemia and/or hyperlipemia, cigarette smoking,
      diabetes mellitus, and metabolic syndrome/obesity) and sexual health. Literature
      was reviewed concerning associations between FSD and presence or absence of
      cardiovascular disease, predictive association of FSD with cardiovascular events,
      and the possibility of vascular risk factor treatment modifying FSD. MAIN OUTCOME
      MEASURE: Main outcome measures used were cardiometabolic risk factors and female
      sexual health, specifically genital arousal. RESULTS: Women treated for
      hypertension have more FSD than normotensives. Women with hyperlipidemia but
      without cardiovascular disease have more FSD than women without hyperlipidemia.
      Women with metabolic syndrome/obesity have more FSD than those without.
      Cardiometabolic risk factors, diabetes, and coronary heart disease are associated
      with more FSD. Data support that treatment of metabolic syndrome/obesity is
      associated with less FSD. Currently, there are no data to support that FSD is a
      predictor of future cardiovascular events. CONCLUSION: Female sexual health is
      complex: there is relative independence between subjective and objective aspects
      of arousal and desire, with numerous contributing factors (hormonal,
      psychological, interpersonal, and social). Based on limited current data, there
      appears to be an association between female sexual health and vascular risk
      factors (hypertension, hyperlipidemia, metabolic syndrome/obesity, diabetes, and
      coronary heart disease). More research is needed.

PMID- 22372653
TI  - Placement of quadratic male sling.

PMID- 22372655
TI  - Sexual function after modified radical hysterectomy (Piver II/Type B) vs. classic
      radical hysterectomy (Piver III/Type C2) for early stage cervical cancer. A
      prospective study.
AB  - INTRODUCTION: When cervical cancer is detected at an early stage (International
      Federation of Gynecology and Obstetrics [FIGO] IA2-IB1), it can be successfully
      treated by radical surgery alone. Considering that most patients are young and
      sexually active at the moment of diagnosis and the long life expectancy of
      survivors after the treatment, quality of life (QoL) and sexual function are
      important issues for cancer survivors and caregivers. However, only a few studies
      have examined the QoL and sexual function in disease-free cervical cancer
      survivors, and there are no studies in the literature comparing prospectively
      sexual function after different types of radical hysterectomy. AIM: To compare
      sexual function in two groups of early stage cervical cancer survivors treated by
      radical surgery alone, undergoing two different types of radical hysterectomy.
      METHODS: Patients treated by radical hysterectomy with systematic lymphadenectomy
      for early stage cervical cancer (FIGO IA2-IB1) have been enrolled and divided in
      two groups with regard to type of radical hysterectomy performed; S1: modified
      radical hysterectomy (Piver II/Type B), S2: classic radical hysterectomy (Piver
      III/ Type C2). MAIN OUTCOME MEASURE: Twenty-four months after surgery we assessed
      the sexual function using the European Organization for Research and Treatment of
      Cancer Cervix Cancer Module Questionnaire, which is a validated system for the
      assessment of disease- and treatment-specific issues that affect the QoL and
      sexual functioning of women who are treated for cervical cancer. RESULTS: Of the
      31 patients enrolled in the S1 group and 46 in the S2 group, 23 and 33 patients
      have been included, respectively. We observed significant differences between the
      two groups in terms of symptom experience, sexual/vaginal functioning, sexual
      activity, and sexual enjoyment. There was not any significant difference
      regarding lymphedema, peripheral neuropathy, and sexual worry. CONCLUSION:
      Survivors of early stage cervical cancer treated by modified radical hysterectomy
      (Piver II/ Type B) have a better sexual function than those operated by classic
      radical hysterectomy (Piver III/ Type C2).

PMID- 22372656
TI  - Determination of storage coefficients during pumping and recovery.
AB  - An aquifer test is used mostly to determine the storage coefficient and
      transmissivity. Although residual drawdown data are widely used in estimating the
      transmissivity of aquifers, the estimation of storage coefficients with recovery
      data is controversial. Some researchers have proposed methods to estimate storage
      coefficients with recovery data by assuming equality of storage coefficients for
      the recovery and pumping periods (S = S'). The aim of this study is to determine
      storage coefficients without such an assumption, that is, S?S'. The method is a
      modified version of Banton-Bangoy's method without considering drawdown data due
      to pumping. Drawdown is plotted vs. the logarithmic ratio (t'/t) or time since
      pumping stopped to the duration of pumping and the ratio of storage coefficient
      during recovery to the storage coefficient from the pumping period (S'/S). The
      method is verified with one case study and two synthetic examples. Thus, it is
      possible to determine storage coefficient of pumping period accurately without
      any data from pumping period by recovery data.

PMID- 22372657
TI  - Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate.
AB  - PURPOSE: The objective of the study was to conjugate the DNA binding ligand para
      [(125)I]-iodoHoechst to octreotate, and to explore the tumour targeting potential
      of this conjugate in the octreotate-somatostatin receptor system. METHODS: We
      synthesized a Hoechst analogue containing a tri-butylstannyl group in the para
      position of phenyl ring, conjugated it to the N-terminal amino group of
      octreotate and prepared (125)I-labelled conjugate by iododestannylation. We used
      the somatostatin receptor (SSTR2) over-expressing cell line A427-7 derived from
      its parent A427 human non-small cell lung carcinoma cell line to investigate
      SSTR2 affinity and receptor-mediated internalisation of the conjugate, and the
      mouse A427-7 tumour xenograft model for in vivo biodistribution studies of the
      radiolabelled conjugate. RESULTS: A method was developed for convenient
      preparation of high specific activity radioiodinated conjugate which retains
      affinity for somatostatin receptors and is internalised into A427-7 SSTR2 over
      expressing cells via a receptor-mediated mechanism. The conjugate accumulates in
      mouse A427-7 tumour xenografts following intravenous administration. CONCLUSIONS:
      A dual targeting strategy for Auger endoradiotherapy, in which a DNA ligand is
      used to target the Auger decay to DNA, in conjunction with receptor-mediated
      targeting to specific receptors, using a labelled DNA ligand/peptide conjugate,
      has been demonstrated for the octreotate-somatostatin receptor system.

PMID- 22372659
TI  - Phytochemical composition of polar fraction of Stachys germanica L. subsp.
      salviifolia (Ten.) Gams, a typical plant of Majella National Park.
AB  - In this study, we report the isolation and identification of several compounds
      present in the polar fraction of Stachys germanica L. subsp. salviifolia (Ten.)
      Gams, collected in the protected area of Majella National Park. In particular, we
      have isolated and identified harpagide, 7-beta-hydroxy-harpagide, ajugol, 5
      allosyloxy-aucubin, verbascoside and, for the first time in this genus, arbutin.

PMID- 22372660
TI  - Solving the Light's criteria misclassification rate of cardiac and hepatic
      transudates.
AB  - BACKGROUND AND OBJECTIVE: Pleural transudates are most commonly due to heart
      failure (HF) or hepatic hydrothorax (HH), but a number of these effusions are
      misclassified as exudates by standard (Light's) criteria. The aim of this study
      was to determine the prevalence of mislabelled transudates and to establish
      simple alternative parameters to correctly identify them. METHODS: We
      retrospectively analysed the pleural fluid and serum protein, lactate
      dehydrogenase and albumin concentrations from 364 cardiac effusions and 102 HH.
      The serum-to-pleural fluid protein and albumin gradients (serum concentration
      minus pleural fluid concentration), as well as the pleural fluid-to-serum albumin
      ratio (pleural fluid concentration divided by the serum concentration) were
      calculated for the mislabelled transudates. RESULTS: Light's criteria had
      misclassified more HF-associated effusions than HH (29% vs 18%, P = 0.002). A
      serum-to-pleural fluid protein gradient >3.1 g/dL correctly identified 55% and
      61% of the HF and HH false exudates, respectively. The figures for an albumin
      gradient >1.2 g/dL were 83% and 62%. Finally, a pleural fluid-to-serum albumin
      ratio <0.6 had identical accuracy for labelling miscategorized cardiac and liver
      related effusions (78% and 77%, respectively). CONCLUSIONS: If the clinical
      picture is consistent with HF but the pleural fluid meets Light's exudative
      criteria, the measurement of the albumin rather than the protein gradient is
      recommended. In the context of cirrhosis, a potentially 'false' exudate is
      identified better by the pleural fluid-to-serum albumin ratio.

PMID- 22372658
TI  - Obesogens, stem cells and the developmental programming of obesity.
AB  - Obesogens are chemicals that directly or indirectly lead to increased fat
      accumulation and obesity. Obesogens have the potential to disrupt multiple
      metabolic signalling pathways in the developing organism that can result in
      permanent changes in adult physiology. Prenatal or perinatal exposure to
      obesogenic endocrine disrupting chemicals has been shown to predispose an
      organism to store more fat from the beginning of its life. For example, excess
      oestrogen or cortisol exposure in the womb or during early life resulted in an
      increased susceptibility to obesity and metabolic syndrome later in life. This
      review focuses on the effects of environmental chemicals, such as the model
      obesogen, tributyltin (TBT), on the development of obesity. We discuss evidence
      linking the obesogenic effects of TBT with its ability to activate the peroxisome
      proliferator-activated receptor gamma and stimulate adipogenesis. We also discuss
      how TBT and other environmental obesogens may lead to epigenetic changes that
      predispose exposed individuals to subsequent weight gain and obesity. This
      suggests that humans, who have been exposed to obesogenic chemicals during
      sensitive windows of development, might be pre-programmed to store increased
      amounts of fat, resulting in a lifelong struggle to maintain a healthy weight and
      exacerbating the deleterious effects of poor diet and inadequate exercise.

PMID- 22372662
TI  - MR-imaging of lumbosacral intervertebral disc degeneration in clinically sound
      German shepherd dogs compared to other breeds.
AB  - German shepherd dogs are overrepresented in the group of dogs with cauda equina
      compression syndrome due to degenerative lumbosacral stenosis. A congenital
      predisposition for early degeneration of the lumbosacral intervertebral disc has
      been suspected. Our aims were to assess the morphologic appearance of the
      lumbosacral intervertebral disc and the lumbosacral junction in healthy German
      shepherd dogs compared to other breeds and to evaluate for an early onset of
      degenerative changes. The lumbosacral spine of 110 clinically sound German
      shepherd dogs and 47 healthy dogs of other large breeds was examined using
      magnetic resonance (MR) imaging. The degeneration of every intervertebral disc
      was graded using an established classification system. Signal intensity of the
      entire lumbosacral disc and the nucleus pulposus was determined independently.
      Lumbosacral malalignment was assessed according to a previously described method.
      The findings for the German shepherd dogs were compared to those of the other
      breeds. Although most dogs were younger than 18 months at the date of
      examination, significantly higher grades of degeneration were detected for the
      lumbosacral intervertebral disc of German shepherd dogs (P < 0.003). Degeneration
      of the lumbosacral intervertebral disc was independent from findings in the other
      lumbar discs. We conclude that the German shepherd dog has a predisposition for
      degenerative changes in the lumbosacral intervertebral disc.

PMID- 22372663
TI  - Air-oxygen helmet-delivered continuous positive airway pressure to manage
      respiratory failure due to bronchiolitis.

PMID- 22372665
TI  - New image analysis of large food particles can discriminate experimentally
      suppressed mastication.
AB  - Objective parameters that could provide a basis for food texture selection for
      elderly or dysphagic patients have not been established. We, therefore, aimed to
      develop a precise method of measuring large particles (>2 mm in diameter) in a
      bolus and an analytical method to provide a scientific rationale for food
      selection under masticatory dysfunction conditions. We developed a new
      illumination system to evaluate the ability of twenty female participants (mean
      age, 23.4 +/- 4.3 years) to masticate carrots, peanuts and beef with full, half
      and one quarter of the number of masticatory strokes. We also evaluated
      mastication under suppressed force, regulated by 20% electromyographic of the
      masseter muscle. The intercept and inclination of the regression line for the
      distribution of large particles were adopted as coefficients for the
      discrimination of masticatory efficiency. Single set of coefficient thresholds of
      0.10 for the intercept and 1.62 for the inclination showed excellent
      discrimination of masticatory conditions for all three test foods with high
      specificity and sensitivity. These results suggested that our method of analysing
      the distribution of particles >2 mm in diameter might provide the basis for the
      appropriate selection of food texture for masticatory dysfunction patients from
      the standpoint of comminution.

PMID- 22372664
TI  - Activation of a plant nucleotide binding-leucine rich repeat disease resistance
      protein by a modified self protein.
AB  - Nucleotide binding-leucine rich repeat (NB-LRR) proteins function as
      intracellular receptors for the detection of pathogens in both plants and
      animals. Despite their central role in innate immunity, the molecular mechanisms
      that govern NB-LRR activation are poorly understood. The Arabidopsis NB-LRR
      protein RPS5 detects the presence of the Pseudomonas syringae effector protein
      AvrPphB by monitoring the status of the Arabidopsis protein kinase PBS1. AvrPphB
      is a cysteine protease that targets PBS1 for cleavage at a single site within the
      activation loop of PBS1. Using a transient expression system in the plant
      Nicotiana benthamiana and stable transgenic Arabidopsis plants we found that both
      PBS1 cleavage products are required to activate RPS5 and can do so in the absence
      of AvrPphB. We also found, however, that the requirement for cleavage of PBS1
      could be bypassed simply by inserting five amino acids at the PBS1 cleavage site,
      which is located at the apex of the activation loop of PBS1. Activation of RPS5
      did not require PBS1 kinase function, and thus RPS5 appears to sense a subtle
      conformational change in PBS1, rather than cleavage. This finding suggests that
      NB-LRR proteins may function as fine-tuned sensors of alterations in the
      structures of effector targets.

PMID- 22372666
TI  - Bacillus thuringiensis protein transfer between rootstock and scion of grafted
      poplar.
AB  - Bacillus thuringiensis (Bt) Cry1Ac protein is a toxin against different leaf
      eating lepidopteran insects that attack poplar trees. In the present study, the
      mode of migration of the Bt-Cry1Ac protein within poplar grafts was investigated.
      Grafting was done using Pb29 (transgenic poplar 741 with cry1Ac genes), CC71
      (transgenic poplar 741 with cry3A genes), non-transgenic poplar 741 and non
      transgenic Populus tomentosa, either as scion or as rootstock. In order to detect
      migration of Bt-Cry1Ac protein from one portion of the graft union to different
      tissues in the grafted plant, ELISA analysis was employed to assess the content
      of Bt-Cry1Ac protein in the phloem, xylem, pith and leaves of the grafted poplar.
      To further verify migration of Bt-Cry1Ac protein, Clostera anachoreta larvae,
      which are susceptible to Bt-Cry1Ac protein, were fed leaves from the control
      graft (i.e., graft portion that originally did not contain Bt-Cry1Ac protein).
      The results showed that Bt-Cry1Ac protein was transported between rootstock and
      scion mainly through the phloem. Migration of Bt-Cry1Ac protein in the grafted
      union was also evidenced in that the leaves of the control graft did have a
      lethal effect on C. anachoreta larvae in laboratory feeding experiments. 

PMID- 22372667
TI  - Role of xanthophylls in light harvesting in green plants: a spectroscopic
      investigation of mutant LHCII and Lhcb pigment-protein complexes.
AB  - The spectroscopic properties and energy transfer dynamics of the protein-bound
      chlorophylls and xanthophylls in monomeric, major LHCII complexes, and minor Lhcb
      complexes from genetically altered Arabidopsis thaliana plants have been
      investigated using both steady-state and time-resolved absorption and
      fluorescence spectroscopic methods. The pigment-protein complexes that were
      studied contain Chl a, Chl b, and variable amounts of the xanthophylls,
      zeaxanthin (Z), violaxanthin (V), neoxanthin (N), and lutein (L). The complexes
      were derived from mutants of plants denoted npq1 (NVL), npq2lut2 (Z),
      aba4npq1lut2 (V), aba4npq1 (VL), npq1lut2 (NV), and npq2 (LZ). The data reveal
      specific singlet energy transfer routes and excited state spectra and dynamics
      that depend on the xanthophyll present in the complex.

PMID- 22372668
TI  - Quantifying hepatic steatosis - more than meets the eye.
AB  - AIMS: The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is the
      histological tool used to assess disease severity based on steatosis,
      inflammation and hepatocyte ballooning. As steatosis contributes up to three of a
      potential eight points to NAS, it is important to quantify steatosis accurately.
      We sought to determine the optimum histological technique for identifying fat in
      tissue. METHODS AND RESULTS: Using tissue from a mouse model of NAFLD, with
      validation in human liver biopsies, the percentage steatosis and fat droplet size
      were assessed in haematoxylin and eosin (H&E)- and Oil Red-O (ORO)-stained
      sections by light microscopy and digital image analysis (DIA). Results were
      compared to biochemical tissue triglyceride content and MRI assessment of hepatic
      lipid content. H&E steatosis assessment correlated poorly with tissue
      triglyceride concentration. However, ORO DIA exhibited much higher sensitivity
      and specificity for steatosis and correlated very well with triglyceride
      concentration in mouse and human liver (R = 0.706, P = 0.001 and R = 0.894, P
      =0.041, respectively). MRI-based assessment of steatosis was inaccurate.
      CONCLUSIONS: ORO DIA is the most accurate method for detecting and quantifying
      steatosis. Although H&E-based NAS remains clinically valid in both clinical
      research and experimental situations, ORO DIA is a more robust technique to
      assess liver steatosis accurately for NAS scoring.

PMID- 22372669
TI  - Synthesis, resolution, and absolute configuration of chiral 4,4'-bipyridines.
AB  - A chiral polyhalogenated 4,4'-bipyridine derivative is described allowing an easy
      access to a new family of chiral 4,4'-bipyridines by site-selective cross
      coupling reactions. The absolute configurations of all the HPLC separated
      enantiomers were determined by X-ray diffraction and electronic circular
      dichroism coupled with time-dependent density functional theory calculations.

PMID- 22372670
TI  - Alcohol intoxication may exacerbate the effects of blunt cranial trauma through
      changes in brain free magnesium levels.
AB  - Moderate to high levels of alcohol decrease brain intracellular free magnesium
      concentration, a factor known to be critical in brain injury. Phosphorus magnetic
      resonance spectroscopy was used to examine changes to brain free magnesium
      concentration after blunt cranial trauma in alcohol-intoxicated rats. Rats
      exposed acutely or chronically to alcohol sufficient to increase blood alcohol
      levels to between 150 and 350 mg/dL demonstrated a brain free magnesium level
      that was 20-50% less than in nonintoxicated animals (p < 0.01). After injury,
      brain free magnesium levels declined more rapidly and to a greater extent in
      alcohol-affected animals than in nonintoxicated control animals (p < 0.001). As
      both preinjury depletion of magnesium and degree of magnesium decline after brain
      injury have been associated with poor recovery, these findings suggest that
      moderate to severe alcohol intoxication may predispose the brain to a worse
      outcome by reducing brain free magnesium levels, both before and after injury.

PMID- 22372671
TI  - Observation status on trial.

PMID- 22372675
TI  - Serum vascular endothelial growth factor in dogs with soft tissue sarcomas.
AB  - This work aimed to evaluate serum vascular endothelial growth factor (VEGF) in 25
      dogs with soft tissue sarcoma, and in 30 healthy dogs. Blood was collected once
      time from the control animals and three times, in the same way, from animals with
      sarcoma. Blood count was performed in the blood collected, and serum VEGF was
      measured by enzyme-linked immunosorbent assay quantitative method. Serum VEGF in
      control animals was similar to patients with soft tissue sarcoma. There was a
      reduction in serum VEGF after the sarcoma resection. There was positive
      correlation between serum VEGF and neutrophil counts, and negative between VEGF
      and hemoglobin content in animals with sarcoma. Animals with hemangiopericytoma
      showed higher serum VEGF levels compared to the patients with malignant
      peripheral nerve sheath. Circulating blood cells can contribute to elevate VEGF
      serum concentrations in dogs with soft tissue sarcomas and a possible role of
      VEGF in the angiogenesis of these tumors. 

PMID- 22372676
TI  - Dehydrative fragmentation of 5-hydroxyalkyl-1H-tetrazoles: a mild route to
      alkylidenecarbenes.
AB  - The development of a mild, base-free method for the generation of
      alkylidenecarbenes is reported. Treatment of 5-hydroxyalkyl-1H-tetrazoles with
      carbodiimides generates products arising from the 1,2-rearrangement or [1,5]-C-H
      bond insertion of a putative alkylidenecarbene. Formation of this divalent
      intermediate is proposed to occur by way of a tetraazafulvene, which undergoes
      extrusion of 2 mol of dinitrogen. Details of this methodology, its application to
      the synthesis of combretastatin A-4, and an improved route to 5-hydroxyalkyl-1H
      tetrazoles are described.

PMID- 22372677
TI  - Nitric oxide in neonatal hypoxemic respiratory failure.
AB  - Nitric oxide (NO) is a cellular signaling molecule and a powerful vasodilator. NO
      modulates basal pulmonary vascular tone and it is important to reduce blood
      pressure and to treat hypoxemic respiratory failure, such as persistent pulmonary
      hypertension (PPHN) in newborns. PPHN is defined as a failure of normal pulmonary
      vascular adaptation at or soon after birth, resulting in a persisting high
      pulmonary vascular resistance. iNO therapy decreases the need of extracorporeal
      membrane oxygenation (ECMO) although it did not reduce mortality of these
      patients. Severe meconial aspiration syndrome is associated with PPHN, resulting
      in severe hypoxemia; iNO administration combined with HFV results in ameliorate
      oxygenation. The cause of hypoxemic respiratory failure in patients with
      congenital diaphragmatic hernia (CDH) is complex. CDH patients experienced
      oxygenation improvement after iNO therapy, but they can be often considered iNO
      poor responders. In some cases iNO therapy can reduce the need of ECMO in
      presurgical stabilization. The pathophysiology of respiratory failure and the
      potential risks differ substantially in preterm infants. Pulmonary hypertension
      can complicate respiratory failure in preterm babies. Current evidence does not
      support use of iNO in early routine, early rescue or layer rescue regimens in the
      care of preterm infants.

PMID- 22372678
TI  - Reference values for airway resistance in newborns, infants and preschoolers from
      a Latin American population.
AB  - BACKGROUND AND OBJECTIVE: Several studies have determined reference values for
      airway resistance measured by the interrupter technique (Rint) in paediatric
      populations, but only one has been done on Latin American children, and no
      studies have been performed on Mexican children. Moreover, these previous studies
      mostly included children aged 3 years and older; therefore, information regarding
      Rint reference values for newborns and infants is scarce. METHODS: Rint
      measurements were performed on preschool children attending eight kindergartens
      (Group 1) and also on sedated newborns, infants and preschool children admitted
      to a tertiary-level paediatric hospital due to non-cardiopulmonary disorders
      (Group 2). RESULTS: In both groups, Rint values were inversely associated with
      age, weight and height, but the strongest association was with height. The linear
      regression equation for Group 1 (n = 209, height 86-129 cm) was Rint = 2.153 -
      0.012 * height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear
      regression equation for Group 2 (n = 55, height 52-113 cm) was Rint = 4.575 -
      0.035 * height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended
      to have slightly higher Rint values than boys, a difference that diminished with
      increasing height. CONCLUSIONS: In this study, Rint reference values applicable
      to Mexican children were determined, and these values are probably also
      applicable to other paediatric populations with similar Spanish-Amerindian
      ancestries. There was an inverse relationship between Rint and height, with
      relatively large between-subject variability.

PMID- 22372679
TI  - New method for site-specific modification of liposomes with proteins using
      sortase A-mediated transpeptidation.
AB  - A new method was developed for site-specific modifications of liposomes by
      proteins via sortase A (SrtA)-mediated transpeptidation reactions. In this
      regard, the enhanced green fluorescent protein (eGFP) was biologically engineered
      to carry at its polypeptide C-terminus the LPATG motif recognized by SrtA and
      used as the protein donor for linking to liposomes that were decorated with
      phospholipids carrying a diglycine motif as the other SrtA substrate and the eGFP
      acceptor. Under the influence of SrtA, eGFP was efficiently attached to
      liposomes, as proved by analyzing the enzymatic reaction products and the
      resultant fluorescent liposomes. It was observed that increasing the
      concentration and the distance of the diglycine motif on and from the liposome
      surface could significantly improve the efficiency of liposome modification by
      proteins. It is anticipated that this strategy can be widely useful for the
      modification of liposomes by other proteins.

PMID- 22372681
TI  - Equine keratomycosis in Japan.
AB  - OBJECTIVE: To describe the incidence, clinical progress, visual outcome, and
      laboratory findings of equine keratomycosis in Japan. PROCEDURE:  Retrospective
      study of the medical records of horses clinically and mycologically diagnosed
      with keratomycosis at the Equine Hospitals of the Japan Racing Association from
      2005 to 2011. RESULTS: The diagnosis of keratomycosis was confirmed in eight
      horses (40.0% of the 20 horses with infectious keratitis from which fungi and/or
      bacteria were isolated). Fungi recovered from corneal swabs were identified as
      Aspergillus flavus (4), Aspergillus niger (1), Fusarium solani (1), and
      Mortierella wolfii (2). All horses were treated medically with topical
      antifungals, and one horse was also treated surgically. The median of treatment
      period was 40 days. Two horses were rendered blind in the affected eye and the
      others retained vision. CONCLUSIONS: Equine keratomycosis comprises a
      considerable portion of infectious keratitis in Japan, and the causative fungi
      that we isolated had been isolated previously from horses with keratomycosis in
      other regions with the exception of M. wolfii. Culture and cytological
      examination of corneal lesions should be immediately performed on eyes with signs
      of keratitis, particularly on those not improving with antibacterial medication,
      as early initiation of aggressive antifungal treatment tended to result in better
      outcome and shorter treatment period.

PMID- 22372682
TI  - In silico fragment-based drug design using a PASS approach.
AB  - Fragment-based drug design integrates different methods to create novel ligands
      using fragment libraries focused on particular biological activities.
      Experimental approaches to the preparation of fragment libraries have some
      drawbacks caused by the need for target crystallization (X-ray and nuclear
      magnetic resonance) and careful immobilization (surface plasmon resonance).
      Molecular modelling (docking) requires accurate data on protein-ligand
      interactions, which are difficult to obtain for some proteins. The main drawbacks
      of QSAR application are associated with the need to collect large homogeneous
      datasets of chemical structures with experimentally determined self-consistent
      quantitative values (potency). We propose a ligand-based approach to the
      selection of fragments with positive contribution to biological activity,
      developed on the basis of the PASS algorithm. The robustness of the PASS
      algorithm for heterogeneous datasets has been shown earlier. PASS estimates
      qualitative (yes/no) prediction of biological activity spectra for over 4000
      biological activities and, therefore, provides the basis for the preparation of a
      fragment library corresponding to multiple criteria. The algorithm for fragment
      selection has been validated using the fractions of intermolecular interactions
      calculated for known inhibitors of nine enzymes extracted from the Protein Data
      Bank database. The statistical significance of differences between fractions of
      intermolecular interactions corresponds, for several enzymes, to the estimated
      positive and negative contribution of fragments in enzyme inhibition.

PMID- 22372683
TI  - Syntheses of chiral N-(protected) tri- and tetrapeptide conjugates.
AB  - Cbz-(protected)-tri- and tetrapeptide conjugates with steroids, sugars, terpenes,
      and heterocycles were prepared using Cbz-(protected)-tri- and
      tetrapeptidoylbenzotriazoles as active intermediates.

PMID- 22372684
TI  - Specification of matrix cleanup goals in fractured porous media.
AB  - Semianalytical transient solutions have been developed to evaluate what level of
      fractured porous media (e.g., bedrock or clay) matrix cleanup must be achieved in
      order to achieve compliance of fracture pore water concentrations within a
      specified time at specified locations of interest. The developed mathematical
      solutions account for forward and backward diffusion in a fractured porous medium
      where the initial condition comprises a spatially uniform, nonzero matrix
      concentration throughout the domain. Illustrative simulations incorporating the
      properties of mudstone fractured bedrock demonstrate that the time required to
      reach a desired fracture pore water concentration is a function of the distance
      between the point of compliance and the upgradient face of the domain where clean
      groundwater is inflowing. Shorter distances correspond to reduced times required
      to reach compliance, implying that shorter treatment zones will respond more
      favorably to remediation than longer treatment zones in which back-diffusion
      dominates the fracture pore water response. For a specified matrix cleanup goal,
      compliance of fracture pore water concentrations will be reached sooner for
      decreased fracture spacing, increased fracture aperture, higher matrix fraction
      organic carbon, lower matrix porosity, shorter aqueous phase decay half-life, and
      a higher hydraulic gradient. The parameters dominating the response of the system
      can be measured using standard field and laboratory techniques.

PMID- 22372685
TI  - Vibrational collective dynamics of dry proteins in the terahertz region.
AB  - The coherent density fluctuations of a perdeuterated dry protein have been
      studied by Brillouin neutron spectroscopy. Besides a nearly wavevector
      independent branch located around 5 meV, a propagating mode with a linear trend
      at low wavevector Q is revealed. The corresponding speed of 3780 +/- 130 m/s is
      definitely higher than that of hydrated proteins. Above Q = 0.8 A(-1), this mode
      becomes overdamped, with lifetimes shorter than 0.1 ps, in fashion similar to
      glassy materials. The present results indicate that dry proteins sustain coherent
      density fluctuations in the THz frequency regime. The trend of the longitudinal
      modulus indicates that in this frequency range dry biomolecules are more rigid
      than hydrated proteins.

PMID- 22372686
TI  - Biomarkers of endocrine disruption: cluster analysis of effects of plasticisers
      on Phase 1 and Phase 2 metabolism of steroids.
AB  - Although some endocrine disruptors (EDs) act at steroid receptors, it is now
      apparent that compounds may have ED potential if they alter steroid synthesis or
      metabolism, particularly if they affect Phase 1 or Phase 2 pathways. In the
      ENDOMET project (EU-funded 5th Framework programme), 23 different assays were
      used on a wide range of EDs. Cluster analysis of the matrix results enabled
      identification of four integrated test systems that can be used to pinpoint
      compounds that are able to alter steroid metabolism or function. Critical
      pathways were shown to include oestrogen synthesis and sulphonation, synthesis of
      sulphate/PAPS and thyroid hormone regulation so that the activity profiles of
      some Phase 1 and Phase 2 reactions can be used as biomarkers for detection of
      compounds with ED potential.

PMID- 22372687
TI  - Differences in seed rain composition in small and large fragments in the
      northeast Brazilian Atlantic Forest.
AB  - Tropical forests are seriously threatened by fragmentation and habitat loss. The
      impact of fragment size and forest configuration on the composition of seed rain
      is insufficiently studied. For the present study, seed rain composition of small
      and large forest fragments (8-388 ha) was assessed in order to identify
      variations in seed abundance, species richness, seed size and dispersal mode.
      Seed rain was documented during a 1-year period in three large and four small
      Atlantic Forest fragments that are isolated by a sugarcane matrix. Total seed
      rain included 20,518 seeds of 149 species of trees, shrubs, palms, lianas and
      herbs. Most species and seeds were animal-dispersed. A significant difference in
      the proportion of seeds and species within different categories of seed size was
      found between small and large fragments. Small fragments received significantly
      more very small-sized seeds (<0.3 cm) and less large-seeded species (>1.5 cm)
      that were generally very rare, with only one species in small and eight in large
      fragments. We found a negative correlation between the inflow of small-sized
      seeds and the percentage of forest cover. Species richness was lower in small
      than in large fragments, but the difference was not very pronounced. Given our
      results, we propose changing plant species pools through logging, tree mortality
      and a high inflow of pioneer species and lianas, especially in small forest
      fragments and areas with low forest cover. Connecting forest fragments through
      corridors and reforestation with local large-seeded tree species may facilitate
      the maintenance of species diversity. 

PMID- 22372688
TI  - Assessment of nontoxic, secondary effects of sorbent amendment to sediments on
      the deposit-feeding organism Neanthes arenaceodentata.
AB  - Activated carbon (AC) amendments to sediments were tested for nontoxic, secondary
      effects on survival, weight change, and energetic biomarkers of the deposit
      feeder Neanthes arenaceodentata. The tests employed silica sand, reference
      sediments, and contaminated sediments. Survival was not affected by the sediment
      type, the AC dose (20% versus 5%), or the AC particle size. Without additional
      food supply, exposure to untreated and AC-amended sediments resulted in similar
      reduction of weight and lipid content, with no difference between ingestible and
      noningestible AC. Overall, whether with or without AC, the organisms showed signs
      of starvation, as the organisms would most likely rely on organic surface
      deposits for their diet in the environments from which the sediments were
      collected. When additional food was supplied, the organisms grew significantly
      and maintained higher lipid and glycogen contents. However, when feeding on fish
      food, organisms grew less in AC amendments with slightly lower lipid and glycogen
      contents relative to organisms exposed to untreated sediment. Batch tests show
      that AC did not sorb sediment-associated nitrogen but sorbed nitrogen from fish
      food. Despite some effects of AC on these deposit feeders, absolute effects of AC
      amendments on growth and energy reserves were not significant.

PMID- 22372690
TI  - Adverse reaction in patients with drug allergy history after simultaneous
      intravenous fundus fluorescein angiography and indocyanine green angiography.
AB  - PURPOSE: To examine the safety of outpatient clinic simultaneous intravenous
      fundus fluorescein angiography (IVFA) and indocyanine green angiography (ICGA) in
      patients with any/all drug allergy history. METHODS: In a single-center
      retrospective study conducted from February 2007 to March 2011, 390 consecutive
      outpatients with drug allergy history and 3426 patients without allergy history
      underwent simultaneous intravenous IVFA and ICGA. The detailed drug allergy
      history, the symptoms and time of the adverse reaction during simultaneous IVFA
      and ICGA were recorded in all the patients. RESULTS: Of the 390 patients with
      drug allergy history who received IVFA and ICGA, 28 patients (7.2%) had an
      adverse reaction. In contrast, 145 of the 3426 patients (4.2%) without allergy
      history had an adverse reaction during simultaneous IVFA and ICGA. Statistical
      significance in the incidence (P=0.008) and severity (P=0.001) of the adverse
      reaction was observed between patients with drug allergy history and those
      without drug allergy history. In 390 patients with drug allergy history, no
      statistical significance was indicated in the incidence of the adverse reaction
      among different types of drug allergy (P>0.05). CONCLUSIONS: Simultaneous IFVA
      and ICGA are generally safe procedures with an acceptable incidence of an adverse
      reaction. However, patients with drug allergy history may have a higher incidence
      and greater severity of an adverse reaction.

PMID- 22372692
TI  - Histopathological and immunohistochemical studies of apocrine sweat gland
      adenocarcinomas in cats.
AB  - Seven adenocarcinomas of apocrine sweat glands among the 67 cutaneous tumours of
      cats were evaluated between 1980 and 2005. Histopathologically, three tumours
      were solid, tubular, tubular-ductal, tubular-cystic and papillar-cystic types
      were also diagnosed each one. Cuboidal and squamous epithelial cells surrounding
      the cystic lumina and their papillar extensions into the cyst lumens were evident
      in almost all tumour types. Besides, fibrovascular stroma which surrounding
      neoplastic foci showed proliferation and stromal invasion. Immunohistochemical
      features of these tumours were examined with pan-cytokeratin, vimentin and
      carcinoembryonic antigen.

PMID- 22372691
TI  - Sustained-release celecoxib from incubated acrylic intraocular lenses suppresses
      lens epithelial cell growth in an ex vivo model of posterior capsule opacity.
AB  - PURPOSE: To determine whether celecoxib (CXB) can be released from incubated
      intraocular lenses (IOLs) sufficiently to inhibit lens epithelial cell (LEC)
      growth in an ex vivo model of posterior capsule opacification (PCO). MATERIALS:
      LEC growth was evaluated for 14 days in canine lens capsules (LCs) that had been
      exposed to media containing 20 MUM CXB for 1-5 days. After the incubation of
      hydrophilic and hydrophobic IOLs in CXB solution, the determination of the in
      vitro release of CXB from the IOLs was performed for up to 28 days. The incubated
      and nonincubated IOLs were evaluated in the ex vivo model of PCO, and the rate of
      LEC growth was evaluated over 28 days. RESULTS: The treatment of LCs with 20 MUM
      CXB for 4 and 5 days completely inhibited LEC growth. LEC repopulation did not
      occur after the removal of CXB. IOLs incubated in CXB for 24 h resulted in a
      sustained release of CXB in vitro at levels theoretically sufficient to inhibit
      PCO. LCs in the ex vivo model of PCO treated with acrylic IOLs incubated in CXB
      had significantly suppressed LEC ingrowth compared with untreated and IOL-only
      LCs. CONCLUSIONS: A 4-day treatment of LCs with a concentration of 20 MUM CXB may
      effectively prevent PCO. IOLs incubated in CXB for 24 h resulted in a sustained
      release of CXB in vitro at levels sufficient to inhibit LEC growth in the ex vivo
      model of PCO. Further studies are needed to determine whether CXB-incubated IOLs
      can effectively prevent the development of PCO in vivo.

PMID- 22372693
TI  - Enantioselective synthesis of (-)-basiliskamide A.
AB  - Basiliskamide A is an antifungal polyketide natural product isolated by Andersen
      and co-workers from a Bacillus laterosporus isolate, PNG-276. A nine-step
      enantioselective synthesis of (-)-basiliskamide A is reported, starting from
      commercially available beta-hydroxy ester 7. The synthesis features a highly
      diastereoselective mismatched double asymmetric delta-stannylallylboration
      reaction of aldehyde 5 with the bifunctional allylborane reagent 4.

PMID- 22372694
TI  - Further investigations into the speed of cerebral swelling following blunt
      cranial trauma.
AB  - An anesthetized sheep model of traumatic brain injury (TBI) has been developed to
      assess early changes in intracranial pressure (ICP) following closed head injury.
      Immediately after TBI, a transient (<10 min) hypertensive response occurred,
      followed by significant and prolonged systemic hypotension. ICP demonstrated a
      biphasic response, being seven times baseline values of 8 +/- 2 mm Hg 10 min
      after injury, decreasing to 25 +/- 2 mm Hg by 30 min, and then increasing to
      values exceeding 30 mm Hg by 4 h postinjury. ICP was always significantly higher
      than baseline values, which combined with hypotension, reduced cerebral perfusion
      pressure to less than 60% of normal. This early and sustained increase in ICP
      after craniocerebral trauma acutely alters cerebral perfusion pressure and brain
      oxygenation and provides a potential pathophysiological explanation for immediate
      clinical manifestations in humans following significant TBI.

PMID- 22372695
TI  - Youth with disabilities' perspectives of the environment and participation: a
      qualitative meta-synthesis.
AB  - Meta-syntheses can enhance our knowledge regarding the impact of the environment
      on the participation of youth with disabilities and generate theoretical
      frameworks to inform policy and best practices. The purpose of this study was to
      describe school-aged youth with disabilities' perspectives regarding the impact
      of the environment and modifications on their participation. A meta-synthesis
      systematically integrates qualitative evidence from multiple studies. Six
      databases were searched and 1287 citations reviewed for inclusion by two
      independent raters; 15 qualitative articles were selected for inclusion. Two
      independent reviewers evaluated the quality of each study and coded the results
      section. Patterns between codes within and across articles were examined using a
      constant comparative approach. Environments may be more or less inclusive for
      youth with disabilities depending upon others' understanding of individual
      abilities and needs, youth involvement in decisions about accommodations, and
      quality of services and policies. Youth implemented strategies to negotiate
      environmental barriers and appraised the quality of their participation based on
      the extent to which they engaged alongside peers. This meta-synthesis generated a
      framework illustrating the relationship between the environment, modifications
      and participation, and provided a conceptualization of participation grounded in
      the lived experiences of youth with disabilities. Findings reveal gaps in current
      knowledge and highlight the importance of involving youth with disabilities in
      decision making.

PMID- 22372696
TI  - Synthesis, gene silencing, and molecular modeling studies of 4'-C-aminomethyl-2'
      O-methyl modified small interfering RNAs.
AB  - The linear syntheses of 4'-C-aminomethyl-2'-O-methyl uridine and cytidine
      nucleoside phosphoramidites were achieved using glucose as the starting material.
      The modified RNA building blocks were incorporated into small interfering RNAs
      (siRNAs) by employing solid phase RNA synthesis. Thermal melting studies showed
      that the modified siRNA duplexes exhibited slightly lower T(m) (~1  degrees
      C/modification) compared to the unmodified duplex. Molecular dynamics simulations
      revealed that the 4'-C-aminomethyl-2'-O-methyl modified nucleotides adopt South
      type conformation in a siRNA duplex, thereby altering the stacking and hydrogen
      bonding interactions. These modified siRNAs were also evaluated for their gene
      silencing efficiency in HeLa cells using a luciferase-based reporter assay. The
      results indicate that the modifications are well tolerated in various positions
      of the passenger strand and at the 3' end of the guide strand but are less
      tolerated in the seed region of the guide strand. The modified siRNAs exhibited
      prolonged stability in human serum compared to unmodified siRNA. This work has
      implications for the use of 4'-C-aminomethyl-2'-O-methyl modified nucleotides to
      overcome some of the challenges associated with the therapeutic utilities of
      siRNAs.

PMID- 22372697
TI  - Facile method for stiff, tough, and strong nanocomposites by direct exfoliation
      of multilayered graphene into native nanocellulose matrix.
AB  - Nanofibrillated cellulose (NFC) is a natural fibrillar material with
      exceptionally high mechanical properties. It has, however, been exceedingly
      difficult to achieve nanocomposites with drastically improved mechanical
      properties by dispersing NFC as random networks to polymer matrices, even using
      compatibilization. We show nanocomposites consisting of aligned assemblies of
      multilayered graphene and NFC with excellent tensile mechanical properties
      without any surface treatments. The optimum composition was found at 1.25 wt %
      graphene multilayers, giving a Young's modulus of 16.9 GPa, ultimate strength of
      351 MPa, strain of 12%, and work-of-fracture of 22.3 MJ m(-3). This combines high
      strength with relatively high toughness and is obtained by direct exfoliation of
      graphite within aqueous hydrogels of NFC where an optimum sonication power is
      described. The results suggest the existence of an attractive interaction between
      multilayered graphene flakes and cellulose. Aligned assemblies are obtained by
      removal of water by filtration. The concept can be beneficial for applications
      because it results in high mechanical properties by a simple and environmentally
      green process.

PMID- 22372698
TI  - 'Nothing is more practical than a good theory': outcome measures in addictions
      treatment research.

PMID- 22372699
TI  - How to measure outcome in clinical trials of substance abuse treatment.

PMID- 22372700
TI  - The mountain roared and brought forth a mouse*: comments on the results of an
      expert panel on standardization of drug dependence treatment trial outcome
      variables.

PMID- 22372701
TI  - More mice or a better mouse trap? Reflections on primary outcome indices in
      illicit drug dependence treatment research.

PMID- 22372702
TI  - Other outcomes in treatments for substance-use disorders: a call for action.

PMID- 22372703
TI  - Commentary on Coulson & Caulkins (2012): Optimizing drug scheduling.

PMID- 22372704
TI  - Commentary on Kurdyak et al. (2012): Methadone and other opioids - need for
      coordinated prescribing.

PMID- 22372706
TI  - 100 years ago in addiction science.

PMID- 22372707
TI  - Depressed adolescents in a case-series were low in vitamin D and depression was
      ameliorated by vitamin D supplementation.
AB  - AIM: The relationship between depression in adolescents and vitamin D was studied
      in a case-series that included effects of vitamin D supplementation. METHODS:
      Serum 25OH vitamin D (25OHD) levels in 54 Swedish depressed adolescents were
      investigated. Subjects with vitamin D deficiency were given vitamin D(3) over 3
      months (n = 48). To evaluate well-being and symptoms related to depression and
      vitamin D status, the WHO-5 well-being scale, the Mood and Feelings Questionnaire
      (MFQ-S) and a vitamin D deficiency scale were used. RESULTS: Mean serum 25OHD in
      the depressed adolescents was 41 at baseline and 91 nmol/L (p < 0.001) after
      supplementation. Basal 25OHD levels correlated positively with well-being (p <
      0.05). After vitamin D supplementation, well-being increased (p < 0.001) and
      there was a significant improvement in eight of the nine items in the vitamin D
      deficiency scale: depressed feeling (p < 0.001), irritability (p < 0.05),
      tiredness (p < 0.001), mood swings (p < 0.01), sleep difficulties (p < 0.01),
      weakness (p < 0.01), ability to concentrate (p < 0.05) and pain (p < 0.05). There
      was a significant amelioration of depression according to the MFQ-S (p < 0.05).
      CONCLUSION: This study showed low levels of vitamin D in 54 depressed
      adolescents, positive correlation between vitamin D and well-being, and improved
      symptoms related to depression and vitamin D deficiency after vitamin D
      supplementation.

PMID- 22372708
TI  - Directed, strong, and reversible immobilization of proteins tagged with a beta
      trefoil lectin domain: a simple method to immobilize biomolecules on plain
      agarose matrixes.
AB  - A highly stable lipase from Geobacillus thermocatenolatus (BTL2) and the enhanced
      green fluorescent protein from Aquorea victoria (EGFP) were recombinantly
      produced N-terminally tagged to the lectin domain of the hemolytic pore-forming
      toxin LSLa from the mushroom  Laetiporus sulphureus . Such a domain (LSL(150)),
      recently described as a novel fusion tag, is based on a beta-trefoil scaffold
      with two operative binding sites for galactose or galactose-containing
      derivatives. The fusion proteins herein analyzed have enabled us to characterize
      the binding mode of LSL(150) to polymeric and solid substrates such as agarose
      beads. The lectin-fusion proteins are able to be quantitatively bound to both
      cross-linked and non-cross-linked agarose matrixes in a very rapid manner,
      resulting in a surprisingly dynamic protein distribution inside the porous beads
      that evolves from heterogeneous to homogeneous along the postimmobilization time.
      Such dynamic distribution can be related to the reversible nature of the LSL(150)
      agarose interaction. Furthermore, this latter interaction is temperature
      dependent since it is 4-fold stronger when the immobilization takes place at 25 
      degrees C than when it does at 4  degrees C. The strongest lectin-agarose
      interaction is also quite stable under a survey of different conditions such as
      high temperatures (up to 60  degrees C) or high organic solvent concentrations
      (up to 60% of acetonitrile). Notably, the use of cross-linked agarose would endow
      the system with more robustness due to its better mechanical properties compared
      to the noncross-linked one. The stability of the LSL(150)-agarose interaction
      would prevent protein leaching during the operation process unless high pH media
      are used. In summary, we believe that the LSL(150) lectin domain exhibits
      interesting structural features as an immobilization domain that makes it
      suitable to reversibly immobilize industrially relevant enzymes in very simple
      carriers as agarose.

PMID- 22372709
TI  - Cytokine gene polymorphisms in the susceptibility to acute coronary syndrome.
AB  - AIM: Acute coronary syndrome (ACS) is an inflammatory disease. Cytokines are the
      central regulators of inflammation and may be a cause or marker of
      atherosclerosis. Accumulating evidence suggests that polymorphisms at promoter
      regions of various cytokine genes are known to be associated with their
      expression levels. In the present study we investigated whether variants at 
      1082G->A (rs1800896) and -592C->A (rs1800872) of interleukin-10 (IL-10), -1188A
      >C (rs3212227) of IL-12 p40, -308G->A of tumor necrosis factor-alpha (TNF-alpha)
      (rs1800629), -174G->C of IL-6 (rs1800795) and +874A->T of interferon-gamma (IFN
      gamma) genes (rs2430561) are associated with ACS. MATERIALS AND METHODS: DNA
      samples were collected from 1083 subjects and IL-10-1082G->A, -592A->C, TNF-alpha
      308G->A, IL-12 p40-1188 A->C, and IFN-gamma+874A->T polymorphisms were identified
      by amplified refractory mutation system polymerase chain reaction and IL-6-174
      G/C, restriction fragment length polymorphism based on standard methods. RESULTS:
      Six hundred and fifty one ACS patients along with 432 age and sex matched
      controls were analyzed for various gene polymorphisms. The "low-producer" IL-10
      1082 AA (chi(2)=9.45; p=0.0021; odds ratio [OR]=1.472; 95% confidence interval
      [CI]=1.15-1.884), "high producer" IL-10-592 CC (chi(2)=39.42; p=0.001, OR=2.26;
      95% CI=1.748-2.292), "low producer"IFN-gamma+874AA (chi(2)=28; p<0.00154; OR=2.36
      & 95% CI=1.713-3.251), and "high producer" TNF-alpha -308AA (chi(2)=3.213,
      p=0.073; OR=1.515) genotypes may be responsible for the regulation of immune
      response leading to inflammation in ACS patients. However, -1188 of the IL-12
      gene was not associated with the disease. CONCLUSION: The polymorphisms at -308G
      >A of TNF-alpha, -174G->C of IL-6, +874A->T of IFN-gamma and -1082G->A, and -592C
      >A of IL-10 genes evaluated in the present study are important risk factors for
      the development of ACS in the South Indian population from Andhra Pradesh. The
      better understanding of these variants conferring susceptibility to ACS may aid
      in early diagnosis and development of new methods to create personalized
      medicine.

PMID- 22372710
TI  - Low priority? A cross sectional study of appearance anxiety in 500 consecutive
      referrals for cosmetic surgery.
AB  - Low priority treatment guidance is used in the National Health Service to manage
      requests for cosmetic surgery where there is no associated functional impairment.
      Provision is made in this guidance to provide surgery on exceptional grounds, and
      this may include significant psychological distress. However, without a good
      understanding of the common factors that underpin requests for surgery, ideally
      in the local population, it is very difficult to define an exception in a clear
      and consistent way. A prospective study of consecutive referrals for cosmetic
      surgery in an NHS plastic surgery unit was therefore completed over a five-year
      period. Five hundred and one men and women aged between 16 and 79 (mean 34.5
      years) were assessed using standardised questionnaires and clinical interview
      carried out by two clinical psychologists specialising in the field. Results
      indicated very marked impact of appearance-related anxiety with significant
      withdrawal from social activities particularly intimate behaviour. Coping
      behaviours ranged from use of concealing clothing and complete social avoidance
      to ominous high risk strategies such as repeated pregnancy with late termination
      to maintain breast size. Treatment goals were predominantly psychosocial. High
      levels of psychological morbidity can be characterised as typical of people
      requesting cosmetic procedures in the NHS rather than exceptional, making the
      achievement of equitable access to limited resources impossible. Rather than
      define this population as 'low-priority', a constructive approach is to examine
      the utility of psychological interventions in a design which evaluates the
      comparative benefits of surgical and psychological approaches to management of
      appearance anxiety.

PMID- 22372711
TI  - Nanochannels: hosts for the supramolecular organization of molecules and
      complexes.
AB  - Nanochannels have been used as hosts for supramolecular organization for a large
      variety of guests. The possibilities for building complex structures based on 2D
      and especially 3D nanochannel hosts are larger than those based on 1D nanochannel
      hosts. The latter are, however, easier to understand and to control. They still
      give rise to a rich world of fascinating objects with very distinguished
      properties. Important changes are observed if the channel diameter becomes
      smaller than 10 nm. The most advanced guest-nanochannel composites have been
      synthesized with nanochannels bearing a diameter of about 1 nm. Impressive
      complexity has been achieved by interfacing these composites with other objects
      and by assembling them into specific structures. This is explained in detail.
      Guest-nanochannel composites that absorb all light in the right wavelength range
      and transfer the electronic excitation energy via FRET to well-positioned
      acceptors offer a unique potential for developing FRET-sensitized solar cells,
      luminescent solar concentrators, color-changing media, and devices for sensing in
      analytical chemistry, biology, and diagnostics. Successful 1D nanochannel hosts
      for synthesizing guest-host composites have been zeolite-based. Among them the
      largest variety of guest-zeolite composites with appealing photochemical,
      photophysical, and optical properties has been prepared by using zeolite L (ZL)
      as a host. The reasons are the various possibilities for fine tuning the size and
      morphology of the particles, for inserting neutral molecules and cations, and for
      preparing rare earth complexes inside by means of the ship-in-a-bottle procedure.
      An important fact is that the channel entrances of ZL-based composites can be
      functonalized and completely blocked, if desired, and furthermore that targeted
      functionalization of the coat is possible. Different degrees of organizational
      levels and prospects for applications are discussed, with special emphasis on
      solar energy conversion devices.

PMID- 22372712
TI  - Clinicopathological characterization of mammary analogue secretory carcinoma of
      salivary glands.
AB  - AIMS: Mammary analogue secretory carcinoma (MASC) is a recently described tumour
      with ETV6 translocation. We aimed to characterize the clinical significance of
      recognizing MASC. METHODS AND RESULTS: Thirty-six patients with MASC (27
      identified retrospectively and nine prospectively) are presented. Historically,
      MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%)
      adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas
      (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one
      of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males
      more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland
      was the most common site of involvement (26 of 36, 72.2%), although other head
      and neck sites, including the base of tongue, were affected. Of 18 patients with
      neck dissection, lymph node involvement was identified in four patients (four of
      18, 22.2%). Survival analysis of MASC cases presented here, combined with those
      reported previously, revealed a mean disease-free survival for patients with MASC
      of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with
      a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P =
      0.43). CONCLUSIONS: Although perhaps slightly more aggressive, MASC clinical
      outcome mimics that of AciCC.

PMID- 22372714
TI  - On the utility of calculating and interpreting apparent storativity.

PMID- 22372713
TI  - pH-dependent complexation of histamine H1 receptor antagonists and human serum
      albumin studied by UV resonance Raman spectroscopy.
AB  - UV resonance Raman spectroscopy was used to characterize the binding of three
      first-generation histamine H(1) receptor antagonists-tripelennamine (TRP),
      mepyramine (MEP), and brompheniramine (BPA)-to human serum albumin (HSA) at pH
      7.2 and pH 9.0. Binding constants differ at these pH values, which can be
      ascribed to the different extent of protonation of the ethylamino side chain of
      the ligands. We have recently shown [Tardioli et al. J. Raman Spectrosc. 2011,
      42, 1016-1024] that for the solution conformation of TRP and MEP the side chain
      plays an important role by allowing an internal hydrogen bond with the
      aminopyridine nitrogen in TRP and MEP. Results presented in this paper suggest
      that the existence of such molecular structures has serious biological
      significance on the binding affinity of those ligands to HSA. At pH 7.2, only the
      stretched conformers of protonated TRP and MEP bind in HSA binding site I. Using
      UV absorption data, we derived binding constants for the neutral and protonated
      forms of TRP to HSA. The neutral species seems to be conjugated to a positive
      group of the protein, affecting both the tryptophan W214 and some of the tyrosine
      (Y) vibrations. BPA, for which the structure with an intramolecular hydrogen
      bonded side chain is not possible, is H bound to the indole ring nitrogen of
      W214, of which the side chain rotates over a certain angle to accommodate the
      drug in site I. We propose that the protonated BPA is also bound in site I, where
      the Y150 residue stabilizes the presence of this compound in the binding pocket.
      No spectroscopic evidence was found for conformational changes of the protein
      affecting the spectroscopic properties of W and Y in this pH range.

PMID- 22372715
TI  - Effects of various degrees of oxidative stress induced by intermittent hypoxia in
      rat myocardial tissues.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the mechanism
      by which oxidative stress induced by chronic intermittent hypoxia (IH) causes
      myocardial damage in obstructive sleep apnoea syndrome. METHODS: A total of 160
      Wistar rats were divided into five experimental groups and subjected to chronic
      IH with different concentrations of oxygen (5%, 7.5%, 10% IH groups; 10%
      continuous oxygen and normoxia control groups). Eight rats from each group were
      sacrificed at the 2-, 4-, 6- and 8-week time points. Superoxide dismutase (SOD)
      activity, malondialdehyde (MDA) levels and total anti-oxidant capability (T-AOC)
      were measured in supernatants of heart homogenates. Expression of the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox)
      and NOX2, and thioredoxin-2 (Trx-2) genes were determined by measuring messenger
      RNA (mRNA) levels by real-time polymerase chain reaction. RESULTS: Compared with
      the control groups, MDA levels increased over time in the IH groups, whereas T
      AOC and SOD activity decreased over time. MDA, T-AOC and SOD activity peaked at 6
      weeks into the IH treatment. The 5% IH group showed significantly higher
      expression of p22(phox) and thioredoxin-2 mRNA, as compared with the other IH
      groups, as well as the control groups. CONCLUSIONS: The severity of oxidative
      stress induced by chronic IH in myocardial tissue was significantly correlated
      with the degree of IH. NADPH oxidase and Trx-2 are important mediators of
      oxidative stress induced by IH.

PMID- 22372716
TI  - Effectiveness of prisms in the management of diplopia in patients due to diverse
      etiologies.
AB  - PURPOSE: To study the effectiveness of prisms in the management of diplopia from
      different etiologies and over a broad range of ocular misalignment. METHODS: In
      this retrospective cohort study, resolution of diplopia in 94 patients who were
      prescribed prisms was studied. RESULTS: Among 94 patients, 88% reported complete
      or partial resolution of double vision (95% confidence interval: 84.1% to 95.6%)
      with highest improvement noted in the divergence insufficiency and skew deviation
      group (100%) compared to 64% improvement noted in patients with convergence
      insufficiency. More than 85% of patients who were prescribed greater than 10
      diopters of prism and those with oblique prism prescriptions also reported
      resolution of diplopia. Eighty-nine percent of the cohort continued with prism
      use and 11% opted for strabismus surgery. CONCLUSION: In this study, prisms were
      effective in alleviation of diplopia over a broad range and for different
      etiologies of double vision.

PMID- 22372717
TI  - Intracranial pathology in young children with apparently isolated nystagmus.
AB  - PURPOSE: To assess the incidence of intracranial pathology in young children who
      had brain magnetic resonance imaging (MRI) to investigate apparently isolated
      nystagmus noted within the first few years of life. METHODS: Retrospective
      institutional review of such children (up to 5 years old). RESULTS: Twenty-six
      patients (17 boys, 9 girls) were identified. Nystagmus was clinically bilateral
      in 22 (85%) and unilateral in 4 (15%). Seventeen cases (65%) were described as
      horizontal pendular nystagmus, 5 (19%) as horizontal jerk nystagmus, 2 (8%) as
      vertical pendular nystagmus, and 1 each as downbeat nystagmus and torsional
      nystagmus (8%). Three of the 26 patients (12%) had significant MRI findings and
      all three had temporal optic nerve head pallor noted during clinical examination.
      Nystagmus was horizontal pendular in two patients and rotary in the third.
      CONCLUSION: The optic nerve head should be carefully assessed for signs of pallor
      in young children with nystagmus and, if present, brain MRI should be performed.
      Otherwise, isolated early childhood nystagmus is unlikely to be associated with
      intracranial pathology. Clinical description of nystagmus did not predict
      intracranial pathology in this cohort.

PMID- 22372718
TI  - Living donor kidney transplantation in crossmatch-positive patients enabled by
      peritransplant immunoadsorption and anti-CD20 therapy.
AB  - Living donor kidney transplantation in crossmatch-positive patients is a
      challenge that requires specific measures. Ten patients with positive crossmatch
      results (n = 9) or negative crossmatch results but strong donor-specific
      antibodies (DSA; n = 1) were desensitized using immunoadsorption (IA) and anti
      CD20 antibody induction. IA was continued after transplantation and accompanied
      by HLA antibody monitoring and protocol biopsies. After a median of 10 IA
      treatments, all patients were desensitized successfully and transplanted. Median
      levels of mean fluorescence intensity (MFI) of Luminex-DSA before desensitization
      were 6203 and decreased after desensitization and immediately before
      transplantation to 891. Patients received a median of seven post-transplant IA
      treatments. At last visit, after a median follow-up of 19 months, 9 of 10
      patients had a functioning allograft and a median Luminex-DSA of 149 MFI; serum
      creatinine was 1.6 mg/dl, and protein to creatinine ratio 0.1. Reversible acute
      antibody-mediated rejection was diagnosed in three patients. One allograft was
      lost after the second post-transplant year in a patient with catastrophic
      antiphospholipid syndrome. We describe a treatment algorithm for desensitization
      of living donor kidney transplant recipients that allows the rapid elimination of
      DSA with a low rate of side effects and results in good graft outcome.

PMID- 22372719
TI  - Triolein embedded cellulose acetate membrane as a tool to evaluate sequestration
      of PAHs in lake sediment core at large temporal scale.
AB  - Although numerous studies have addressed sequestration of hydrophobic organic
      compounds (HOCs) in laboratory, little attention has been paid to its evaluation
      method in field at large temporal scale. A biomimetic tool, triolein embedded
      cellulose acetate membrane (TECAM), was therefore tested to evaluate
      sequestration of six PAHs with various hydrophobicity in a well-dated sediment
      core sampled from Nanyi Lake, China. Properties of sediment organic matter (OM)
      varying with aging time dominated the sequestration of PAHs in the sediment core.
      TECAM-sediment accumulation factors (MSAFs) of the PAHs declined with aging time,
      and significantly correlated with the corresponding biota-sediment accumulation
      factors (BSAFs) for gastropod (Bellamya aeruginosa) simultaneously incubated in
      the same sediment slices. Sequestration rates of the PAHs in the sediment core
      evaluated by TECAM were much lower than those obtained from laboratory study. The
      relationship between relative availability for TECAM (MSAF(t)/MSAF(0)) and aging
      time followed the first order exponential decay model. MSAF(t)/MSAF(0) was well
      related to the minor changes of the properties of OM varying with aging time.
      Compared with chemical extraction, sequestration reflected by TECAM was much
      closer to that by B. aeruginosa. In contrast to B. aeruginosa, TECAM could avoid
      metabolism and the influences from feeding and other behaviors of organisms, and
      it is much easier to deploy and ready in laboratory. Hence TECAM provides an
      effective and convenient way to study sequestration of PAHs and probably other
      HOCs in field at large temporal scale.

PMID- 22372720
TI  - Fabrication of a hollow obturator as a single unit for management of bilateral
      subtotal maxillectomy.
AB  - Prosthetic rehabilitation with an obturator for a total or subtotal maxillectomy
      patient is a challenging task, as there are little or no residual maxillary
      structures to depend on for support, retention, and stability of the prosthesis.
      This clinical report describes the prosthodontic management of a patient operated
      on for a bilateral subtotal maxillectomy secondary to ameloblastoma of the palate
      with a closed hollow obturator. The processing technique described in this
      article to fabricate the hollow obturator is a variation of other well-known
      techniques. The variation comprises the use of a wax bolus to maintain a
      predictable internal dimension for a hollow obturator. This technique allows
      fabrication of a complete hollow obturator prosthesis as a single unit in heat
      polymerized acrylic resin using a single-step flasking procedure.

PMID- 22372721
TI  - Single-session primary high-intensity focused ultrasonography treatment for
      localized prostate cancer: biochemical outcomes using third generation-based
      technology.
AB  - What's known on the subject? and What does the study add? The experience with
      HIFU as a minimally invasive treatment for localized prostate cancer is
      relatively new and most reports are from European centres. Our study is unique in
      five regards: 1. Data was collected prospectively. 2. All patients were treated
      with contemporary technology. 3. Outcomes are reported after a single HIFU
      session using two definitions of biochemical failure that have the ability to
      predict longer-term clinical failure after primary ablative therapies for
      prostate cancer (Stuttgart definition for HIFU and Horwitz definition for
      radiation). 4. All patients were treated in a single centre. 5. No patients
      underwent peri-HIFU TURP. The present study represents the largest North American
      prospective cohort of primary HIFU for prostate cancer with mid-term oncological
      outcome data. OBJECTIVE: To assess 4-year biochemical failure (BCF) rates in
      patients after high-intensity focused ultrasonography (HIFU) treatment using the
      Horwitz and Stuttgart definitions. PATIENTS AND METHODS: A total of 447
      consecutive patients were treated with a single session of HIFU between May 2005
      and December 2010. Follow-up included prostate-specific antigen (PSA) measurement
      every 3 months during the first year and every 6 months thereafter. Patients who
      had previously received radiation, androgen deprivation or HIFU therapy, and
      patients with <2 consecutive PSA measurements were excluded. BCF was reported
      using the Stuttgart (PSA nadir + 1.2 ng/mL rising) and the Horwitz (two
      consecutive increases of at least 0.5 ng/mL) definitions. RESULTS: In all, 402
      patients met the inclusion criteria and the median (range) follow-up was 24 (6
      48) months. Of these patients, 183 (45.5%) had low and 219 (54.5%) had
      intermediate D'Amico's risk stratification disease. Mean and median absolute PSA
      nadir levels were 0.36 +/- 0.69 and 0.1 ng/mL (Q(1):0, Q(3):0.37), respectively
      and these were achieved in median time of 3 months. Overall 4-year mean (range)
      BCF-free rates were 68 (61-75)% and 72 (68-77)% according to the Stuttgart and
      Horwitz definitions at 4 years, respectively. Mean (range) BCF-free rates were
      significantly higher for a PSA nadir <=0.5 ng/mL and prostate volume <=30 mL for
      both definitions at 4-year follow-up [Stuttgart: 79 (72-86)% vs. 25 (13-38)%;
      Horwitz: 82 (77-87)% vs. 33 (21-44)%] and [Stuttgart: 72 (64-79)% vs. 56 (42
      69)%; Horwitz: 75 (69-80)% vs. 63 (53-74)%], respectively. Pre-treatment PSA and
      PSA nadir of >0.5 ng/mL were the predictors of BCF using both definitions.
      CONCLUSIONS: Primary HIFU appears to result in promising 4-year BCF-free rates in
      individuals with low- and intermediate-risk prostate cancer who achieve PSA nadir
      <0.5 ng/mL. A prostate volume <30 mL is associated with PSA nadir levels of <0.5
      ng/mL suggesting a potential role for pretreatment volume reduction (medically or
      surgically) in larger prostates.

PMID- 22372722
TI  - Neuronal c-Jun is required for successful axonal regeneration, but the effects of
      phosphorylation of its N-terminus are moderate.
AB  - Although neural c-Jun is essential for successful peripheral nerve regeneration,
      the cellular basis of this effect and the impact of c-Jun activation are
      incompletely understood. In the current study, we explored the effects of neuron
      selective c-Jun deletion, substitution of serine 63 and 73 phosphoacceptor sites
      with non-phosphorylatable alanine, and deletion of Jun N-terminal kinases 1, 2
      and 3 in mouse facial nerve regeneration. Removal of the floxed c-jun gene in
      facial motoneurons using cre recombinase under control of a neuron-specific
      synapsin promoter (junDeltaS) abolished basal and injury-induced neuronal c-Jun
      immunoreactivity, as well as most of the molecular responses following facial
      axotomy. Absence of neuronal Jun reduced the speed of axonal regeneration
      following crush, and prevented most cut axons from reconnecting to their target,
      significantly reducing functional recovery. Despite blocking cell death, this was
      associated with a large number of shrunken neurons. Finally, junDeltaS mutants
      also had diminished astrocyte and microglial activation and T-cell influx,
      suggesting that these non-neuronal responses depend on the release of Jun
      dependent signals from neighboring injured motoneurons. The effects of
      substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global
      deletion of individual kinases responsible for N-terminal c-Jun phosphorylation
      were mild. junAA mutants showed decrease in neuronal cell size, a moderate
      reduction in post-axotomy CD44 levels and slightly increased astrogliosis.
      Deletion of Jun N-terminal kinase (JNK)1 or JNK3 showed delayed functional
      recovery; deletion of JNK3 also interfered with T-cell influx, and reduced CD44
      levels. Deletion of JNK2 had no effect. Thus, neuronal c-Jun is needed in
      regeneration, but JNK phosphorylation of the N-terminus mostly appears to not be
      required for its function.

PMID- 22372723
TI  - Efficacy of antiresorptive agents for preventing fractures in Japanese patients
      with an increased fracture risk: review of the literature.
AB  - The aim of the present review was to clarify the efficacy of currently available
      potent antiresorptive agents for preventing fractures in Japanese patients with
      an increased fracture risk. PubMed was used to search the literature for
      randomized controlled trials (RCTs), with the following search terms: fracture,
      etidronate, alendronate, risedronate, minodronate, raloxifene, bazedoxifene and
      Japan. The inclusion criteria were papers written in English, >=50 subjects per
      group and a study period of >=1 year. Fourteen RCTs met these criteria. The
      efficacy of antiresorptive agents for preventing vertebral, nonvertebral and hip
      fractures was investigated. There was evidence that raloxifene reduced the
      incidence of clinical vertebral fractures, while etidronate, alendronate and
      minodronate (but not bazedoxifene) reduced the incidence of morphometric
      vertebral fractures in patients with postmenopausal or involutional osteoporosis.
      Head-to-head trials showed that alendronate and raloxifene had similar efficacy
      for preventing vertebral fractures in patients with postmenopausal osteoporosis,
      while risedronate was not inferior to etidronate for reducing the incidence of
      morphometric vertebral fractures in patients with involutional osteoporosis.
      Alendronate reduced the incidence of hip fractures in patients with Parkinson's
      disease, and risedronate reduced the incidence of nonvertebral fractures and hip
      fractures in patients with Alzheimer's disease or stroke. In conclusion, the
      present review confirmed the efficacy of etidronate, minodronate and raloxifene
      for the prevention of vertebral fractures, the efficacy of alendronate for
      vertebral and hip fractures, and the efficacy of risedronate for vertebral,
      nonvertebral and hip fractures in Japanese patients with an increased fracture
      risk.

PMID- 22372724
TI  - Use of clarithromycin and adverse cardiovascular events among older patients
      receiving donepezil: a population-based, nested case-control study.
AB  - BACKGROUND: Donepezil is a commonly used drug in older people that due to its
      procholinergic effects can provoke bradycardia and neurocardiogenic syncope.
      Donepezil is metabolized by the cytochrome P450 isozyme 3A4 (CYP3A4).
      Clarithromycin is a potent inhibitor of CYP3A4, and patients taking both of these
      drugs may be at increased risk of cardiac adverse events. OBJECTIVE: The aim of
      this study was to evaluate the association between recent use of clarithromycin
      and adverse cardiovascular events in elderly patients receiving donepezil.
      METHODS: A population-based, nested case-control study using provincial
      healthcare databases was conducted. The base cohort was made up of persons 66
      years of age or older who were prescribed donepezil and also were prescribed
      clarithromycin, erythromycin, azithromycin, cefuroxime, moxifloxacin or
      levofloxacin. Cases were those members of the base cohort hospitalized for
      bradycardia, syncope or complete atrioventricular block. For each case patient,
      five controls were matched according to age, sex and residence (community or long
      term care). RESULTS: Between July 2002 and March 2010, 17,712 patients
      continuously receiving donepezil were prescribed one of the antibacterials. In
      1400 person-years of follow-up, 59 cases were identified. As compared with
      azithromycin, there was no statistically significant association between use of
      clarithromycin in donepezil users and subsequent adverse cardiovascular events
      (odds ratio 0.67; 95% CI 0.28, 1.63). There was no significant risk associated
      with exposure to either cefuroxime or respiratory quinolones. CONCLUSIONS: The
      use of clarithromycin in elderly donepezil users did not significantly increase
      the risk of adverse cardiovascular outcomes. However, our study cannot rule out a
      possible small increase in risk. Although antibacterials can be beneficial, care
      should be taken in selecting antibacterials for use in older people receiving
      donepezil.

PMID- 22372725
TI  - Adverse drug reaction-related hospitalizations in persons aged 55 years and over:
      a population-based study in the Netherlands.
AB  - BACKGROUND: Elderly individuals appear to be particularly at risk of developing
      adverse drug reactions (ADRs) because of higher rates of polypharmacy, age
      related pharmacokinetic changes, pharmacodynamic variations and substantial co
      morbidity levels. Thus, the increasing contribution of elderly individuals to the
      total population means ADR-related hospitalizations are expected to become more
      frequent. However, a recent study conducted in the Netherlands found that ADR
      related hospitalizations had stabilized during the years 1997-2007. Nonetheless,
      this study did not take into account the number of medicines used. OBJECTIVES:
      Therefore, the objectives of this study were to describe the association between
      age and sex, and the risk of an adverse drug reaction (ADR)-related
      hospitalization in persons aged 55 years and over in the Netherlands and to
      correlate these ADR-related hospitalizations with the number of dispensed
      medicines over the same period. METHODS: Data on hospital admissions were
      obtained from the Dutch nationwide registry of hospital discharges. Data from
      Statistics Netherlands were used to obtain population demographics. Data on
      dispensed medicinal products were obtained from the Dutch Foundation for
      Pharmaceutical Statistics. Analyses were performed by calculating relative risks
      (RRs). RESULTS: Those aged >=75 years were at a more than 4-fold increased risk
      of being hospitalized in comparison with those aged 55-64 years (RR 4.15; 95% CI
      4.12, 4.18). In addition, female sex was associated with an increased risk of an
      ADR-related hospitalization (RR 1.05; 95% CI 1.03, 1.08) in comparison with
      males. When taking into account the number of dispensings, elderly >=75 years of
      age were at an increased risk of being hospitalized for an ADR due to
      anticoagulants (RR 2.20; 95% CI 2.12, 2.28), antidiabetic agents (RR 3.53; 95% CI
      3.39, 3.66), salicylates (RR 1.70; 95% 1.54, 1.86) and antirheumatics (RR 2.19;
      95% CI 2.06, 2.33). CONCLUSION: In our study, we showed that elderly aged >=75
      years were at increased risk of an ADR-related hospitalization. Given that the
      number of elderly and very old will continue to grow, it is of pivotal importance
      to further endorse drug safety in this vulnerable patient group.

PMID- 22372726
TI  - Acetylsalicylic acid/esomeprazole fixed-dose combination.
AB  - The fixed-dose acetylsalicylic acid (ASA)/esomeprazole capsule combines the
      cardiovascular (CV) protective effects of low-dose ASA with the gastroprotective
      effects of the proton pump inhibitor esomeprazole. It is approved for use as a
      convenient once-daily regimen in the prevention of CV and cerebrovascular events
      in patients requiring continuous low-dose ASA who are at risk of developing
      gastric and/or duodenal (peptic) ulcers. In two large, 26-week, randomized,
      double-blind, multinational, phase III trials (ASTERIX and OBERON) in patients
      who were receiving low-dose ASA for the prevention of CV events and who had an
      increased risk of ulcer development, the incidence of endoscopy-proven peptic
      ulcers (primary endpoint) was significantly lower with the addition of
      esomeprazole 20 mg/day versus placebo. Moreover, patient-reported dyspeptic
      symptoms (epigastric pain and epigastric burning) were reported in significantly
      fewer patients in the low-dose ASA plus esomeprazole group than in the low-dose
      ASA plus placebo group. Low-dose ASA plus esomeprazole treatment was generally
      well tolerated, with a similar adverse event profile to that seen with low-dose
      ASA plus placebo.

PMID- 22372727
TI  - Abiraterone acetate: a guide to its use in metastatic castration-resistant
      prostate cancer.
AB  - Oral abiraterone acetate (Zytiga(r)), a selective cytochrome P450 17A1 enzyme
      inhibitor, is used in combination with prednisone or prednisolone to treat
      patients with metastatic castration-resistant prostate cancer (CRPC) who have
      previously received docetaxel-containing chemotherapy. In a clinical trial in
      patients with CRPC, abiraterone acetate plus prednisone significantly prolonged
      overall survival, the time to prostate-specific antigen progression and
      progression-free survival compared with placebo plus prednisone.

PMID- 22372728
TI  - Multi-compartment compliance AIDS: friend or foe?

PMID- 22372730
TI  - Fetal growth and later maternal death, cardiovascular disease and diabetes.
AB  - OBJECTIVES: Low birthweight of the offspring has been associated with increased
      risk of early death and ischemic heart disease in the mother. However, other
      measurements of fetal growth than the basic birthweight are more accurate. We
      investigated the relation between the standardized birthweight by gestational age
      and gender and the ponderal index and the mother's subsequent mortality and
      cardiovascular morbidity. DESIGN: Registry-based retrospective cohort study.
      SETTING: Women with a first singleton delivery in Denmark from 1978 to 2007.
      POPULATION: 782 287 women followed for 14.6 years yielding 11 600 945 person
      years. METHODS: Cox proportional hazard models. MAIN OUTCOME MEASURES: The
      primary exposures were variation in the standardized birthweight and ponderal
      index. The endpoints were subsequent maternal death, hypertension, ischemic heart
      disease, stroke, thrombosis, and diabetes mellitus. RESULTS: The risk-profile for
      the standardized birthweight and subsequent maternal death had a nadir between 
      0.5 and -1 SD (HR 0.91; 95%CI 0.83-1.00) and increased with decreasing fetal
      growth peaking at <-3 SD (HR 2.75; 95%CI 2.37-3.19) compared to the median. The
      risk-profile for subsequent diabetes mellitus by standardized ponderal index had
      a nadir between +0.5 to +1 SD (HR 0.82; 95%CI 0.76-0.89) rising with increasing
      fetal growth and peaking at >+3 SD (HR 17.8; 95%CI 15.0-21.0). The risk-profiles
      for standardized ponderal index paralleled those for birthweight, but with
      smaller risk estimates. Adjusting for other pregnancy complications diminished
      the estimates. CONCLUSION: The fetal growth is a marker of subsequent risk for
      premature death, cardiovascular disease, and diabetes mellitus in the mother.

PMID- 22372731
TI  - Rights of the newborn and end-of-life decisions.
AB  - Advances in perinatal medicine have dramatically improved neonatal survival. End
      of-life decision making for newborns with adverse prognosis is an ethical
      challenge and the ethical issues are controversial. The newborn is a person with
      specific rights which he cannot claim, due to his physical and mental immaturity.
      These rights impose to the society obligations and responsibilities, which health
      professionals and institutions of all countries must enforce. Every newborn has
      the right to life with dignity. Providing compassionate family-centered end-of
      life care to infants and their families in the NICU should be a mandatory
      component of an optimally neonatal palliative care.

PMID- 22372732
TI  - Three-dimensional stereophotogrammetrical analysis of peristomal fixation of
      adhesive base plates during hands-free speech among laryngectomised patients
      related to tracheostoma volumes.
AB  - OBJECTIVES: This study evaluates the relation between stoma volumes by means of
      objective three-dimensional measurements of laryngectomised individuals and
      peristomal fixation of adhesive baseplates during hands-free speech. DESIGN: A
      three-dimensional stereophotogrammetrical image was captured of the tracheostoma
      and its surrounding tissue for each participant. The placement of a baseplate
      adhesive was virtually simulated. Individual stoma volumes were calculated and
      related to the duration of lifetime of adhesive baseplates. SETTING: Prospective
      trial in a university hospital setting. PARTICIPANTS: Twenty-four laryngectomised
      patients. MAIN OUTCOME MEASURES: Stoma volume in cm(3) and adhesive baseplate
      adherence in minutes. RESULTS: For the 24 three-dimensional images captured, the
      mean volume of the area under the adhesive (stoma volume) was 9.5 cm(3) (range
      3.5-22.5). After relating the different volumes of all patients to their
      individual fixation score, a significant decrease in duration of adhesive
      lifetime was found with increasing volumes of the stoma (P = 0.001). An increase
      of 1 cm(3) in tracheostoma volume resulted in a decrease of 21% in median
      adhesive lifetime (95% confidence interval 10-31%). CONCLUSIONS: Longer lifetime
      of the adhesive baseplate in patients with smaller volume outcomes suggests that
      a more accurate fit between baseplate and stoma leads to better fixation. This
      should be taken into account when shaping a stoma during laryngectomy. On the
      other hand, a more custom-made patch that has a more accurate fit could increase
      the lifetime of fixation. We believe that our three-dimensional volumetric data
      can contribute to the development of such an adhesive.

PMID- 22372733
TI  - Synthesis of silyloxy dienes by silylene transfer to divinyl ketones: application
      to the asymmetric synthesis of substituted cyclohexanes.
AB  - Silver-catalyzed silylene transfer to divinyl ketones provided 2-silyloxy-1,3
      dienes with control of stereochemistry and regioselectivity. The products
      participated in Diels-Alder reactions with electron-deficient alkenes and imines
      to form six-membered-ring products diastereoselectively. Cycloaddition reactions
      with alkenes bearing chiral auxiliaries provided access to chiral, nonracemic
      cyclohexenes. The methodology, therefore, represents a synthesis of
      diastereomerically and enantiomerically pure products in a single flask. The
      highly substituted cyclohexene products could be functionalized stereoselectively
      to provide cyclohexanols after oxidation of the carbon-silicon bond.

PMID- 22372734
TI  - Nucleoside transport across the plasma membrane mediated by equilibrative
      nucleoside transporter 3 influences metabolism of Arabidopsis seedlings.
AB  - The metabolism of nitrogen-rich nucleosides in Arabidopsis seedlings was
      investigated at the level of import and subsequent salvage or degradation. Uptake
      and fate of nucleosides imported by equilibrative nucleoside transporter 3 (ENT3)
      was analysed and, furthermore, a comprehensive analysis of the effect of
      exogenously fed nucleosides at the level of metabolic as well as transcriptomic
      alterations was performed. Expression of nucleoside transporters ENT1 and ENT3,
      together with nucleoside import, was increased upon nitrogen limitation. Thereby
      a role for ENT3, which is expressed mainly in the vasculature of roots and
      leaves, as a major import route for nucleosides was supported. Exogenously fed
      nucleosides were able to attenuate nitrogen starvation effects such as
      chlorophyll breakdown, anthocyanin accumulation, RNA breakdown and reduced levels
      of amino acids. In response to nucleoside supply, up-regulation of genes involved
      in nitrogen distribution in plants was observed. In addition, genes involved in
      nucleoside metabolism were identified as regulated upon nitrogen limitation. In
      summary, an overall beneficial effect of nucleoside supply to Arabidopsis
      seedlings, especially under limiting nitrogen conditions, was observed. 

PMID- 22372735
TI  - Effect of light-emitting diode colour temperature on magnifier reading
      performance of the visually impaired.
AB  - BACKGROUND: As light-emitting diodes become more common as the light source for
      low vision aids, the effect of illumination colour temperature on magnifier
      reading performance was investigated. METHODS: Reading ability (maximum reading
      speed, critical print size, threshold near visual acuity) using Radner charts and
      subjective preference was assessed for 107 participants with visual impairment
      using three stand magnifiers with light emitting diode illumination colour
      temperatures of 2,700 K, 4,500 K and 6,000 K. The results were compared with
      distance visual acuity, prescribed magnification, age and the primary cause of
      visual impairment. RESULTS: Reading speed, critical print size and near visual
      acuity were unaffected by illumination colour temperature (p > 0.05). Reading
      metrics decreased with worsening acuity and higher levels of prescribed
      magnification but acuity was unaffected by age. Each colour temperature was
      preferred and disliked by a similar number of patients and was unrelated to
      distance visual acuity, prescribed magnification and age (p > 0.05). Patients had
      better near acuity (p = 0.002), critical print size (p = 0.034) and maximum
      reading speed (p < 0.001), and the improvement in near from distance acuity was
      greater (p = 0.004) with their preferred rather than least-liked colour
      temperature illumination. CONCLUSION: A range of colour temperature illuminations
      should be offered to all visually impaired individuals prescribed with an optical
      magnifier for near tasks to optimise subjective and objective benefits.

PMID- 22372736
TI  - Towards big data science in the decade ahead from ten years of InCoB and the 1st
      ISCB-Asia Joint Conference.
AB  - The 2011 International Conference on Bioinformatics (InCoB) conference, which is
      the annual scientific conference of the Asia-Pacific Bioinformatics Network
      (APBioNet), is hosted by Kuala Lumpur, Malaysia, is co-organized with the first
      ISCB-Asia conference of the International Society for Computational Biology
      (ISCB). InCoB and the sequencing of the human genome are both celebrating their
      tenth anniversaries and InCoB's goalposts for the next decade, implementing
      standards in bioinformatics and globally distributed computational networks, will
      be discussed and adopted at this conference. Of the 49 manuscripts (selected from
      104 submissions) accepted to BMC Genomics and BMC Bioinformatics conference
      supplements, 24 are featured in this issue, covering software tools,
      genome/proteome analysis, systems biology (networks, pathways, bioimaging) and
      drug discovery and design.

PMID- 22372737
TI  - Disruptive behaviour disorders: a systematic review of environmental antenatal
      and early years risk factors.
AB  - Disruptive behaviour disorders (DBDs), including attention-deficit/hyperactivity
      disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD)
      are chronic disorders with significant overlap in aetiology and presentation. An
      integrative examination of environmental risk factors is lacking. Six literature
      searches of web-based bibliographic databases were completed to identify
      literature on DBDs in general and five disorders in particular: CD, ODD, ADHD,
      deficits of attention, motor control and perception, and reactive attachment
      disorder. Searches were filtered to focus on studies including diagnostic
      assessment, focussing on environmental risk and protective factors in the first 4
      years of life. The database searches generated 9806 papers of which 47 were
      reviewed after filters had been applied. The evidence suggests links between a
      number of early life risk factors and DBDs, including prenatal cigarette smoking
      and alcohol use, prenatal viral illness, maternal stress and anxiety, low
      birthweight, peri-partum and early neonatal complications, parental stress and
      parenting styles in infancy, early deprivation, adoption and separation. Despite
      the understanding that there is sharing of risk factors between the DBDs, there
      has been a disproportionate focus on the role of certain risk factors at the
      expense of others and the field is weakened by difficulties in controlling for
      all potential confounding variables.

PMID- 22372738
TI  - Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a
      potential biomarker for hepatocellular carcinoma.
AB  - BACKGROUND: The heterogeneous nature of hepatocellular carcinoma (HCC) and the
      lack of appropriate biomarkers have hampered patient prognosis and treatment
      stratification. To identify a new prognostic biomarker that is related to human
      telomerase reverse transcriptase (hTERT) in HCC, we employed a unique proteomics
      approach using liquid chromatograph-mass spectrometry/mass spectrometry (LC
      MS/MS) after gel filtration purification of liver tissue. METHODS: Protein
      lysates from HCC and cirrhotic liver tissue were subjected to gel filtration
      using high performance liquid chromatography. The telomerase complex was
      identified at a molecular mass of 350 kDa in parallel with telomerase activity.
      These fractionated lysates of 350 kDa were analyzed by LC-MS/MS. The relation of
      the identified marker and prognosis was statistically examined in surgically
      resected HCC patients. RESULTS: We identified 24 differentially expressed
      proteins in HCC. One of these proteins, heterogeneous nuclear ribonucleoprotein
      A2/B1 (hnRNP A2/B1), was further analyzed by immunoprecipitation assay using
      tissue and cell line samples and found to interact with hTERT. Moreover small
      interfering RNA against hnRNP A2/B1 suppressed telomerase activity, and
      immunohistochemical examination showed that the enhanced nuclear and cytoplasmic
      hnRNP A2/B1 expression in HCC was significantly associated with histological
      grade of tumor differentiation and microvascular invasion of HCC. Furthermore,
      survival analysis of 74 HCC patients who received curative surgical treatment
      showed that hnRNP A2/B1 expression is an independent prognostic factor for
      patient survival. CONCLUSIONS: Heterogeneous nuclear ribonucleoprotein A2/B1, an
      hTERT-associated protein, is a potential prognostic biomarker for HCC patients
      and might be a therapeutic target of HCC.

PMID- 22372740
TI  - The future of testis research is turning 6! Six years of international network
      for young researchers in male fertility.
AB  - The 'International Network for Young Researchers in Male Fertility' has now
      turned 6 years old and offers a platform that stimulates scientific exchange as
      well as the development of international cooperation for young researchers. We
      report on our scope and the exciting achievements, amongst others, the
      continually increasing number of participants and the growing success of our
      annual meetings.

PMID- 22372739
TI  - Development of multifunctional hyaluronan-coated nanoparticles for imaging and
      drug delivery to cancer cells.
AB  - Currently, there is high interest in developing multifunctional theranostic
      platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan
      (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising
      system for targeted imaging and drug delivery. When incubated with cancer cells,
      HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer
      cells was much higher than the NPs without HA coating. The high magnetic
      relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance
      imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the
      nanoparticles through an acid responsive linker. While HA-SPION was not toxic to
      cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug
      sensitive but also multi-drug-resistant cancer cells. This was attributed to
      differential uptake mechanisms and cellular distributions of free DOX and DOX-HA
      SPION in cancer cells.

PMID- 22372741
TI  - Nonoccupational postexposure prophylaxis following sexual assault in
      industrialized low-HIV-prevalence countries: a review.
AB  - Although available for over a decade, use of nonoccupational postexposure
      prophylaxis (nPEP) remains controversial in the United States. There are concerns
      over sexual assault survivors' adherence, or lack thereof, leading to increased
      costs without an appreciable decrease in human immunodeficiency virus (HIV)
      transmission. This review examines and synthesizes the available literature from
      the past 10 years to determine the true rates of provision and adherence to nPEP
      regimens in sexual assault survivors in low HIV prevalence, industrialized
      nations. Findings suggest that further prospective research is necessary to
      better understand the process of post-assault nPEP evaluation and subsequent
      follow-up and adherence.

PMID- 22372742
TI  - Effect of several antioxidants on thawed ram spermatozoa submitted to 37 degrees
      C up to four hours.
AB  - Thawed ram spermatozoa were incubated at 37 degrees C in the presence of
      dehydroascorbic acid (DHA), TEMPOL (TPL), N-acetyl-cysteine (NAC) and rutin
      (RUT), at 0.1 and 1 mm, in order to test their effects on sperm physiology.
      Cryopreserved spermatozoa from four rams were thawed, pooled, washed and
      incubated in TALP-Hepes with 1 mm or 0.1 mm of each antioxidant, performing a
      replicate with induced oxidative stress (Fe(2+) /ascorbate). Motility (CASA),
      viability and mitochondrial membrane potential (flow cytometry) were analysed at
      2 and 4 h. Lipoperoxidation (MDA production), intracellular reactive oxygen
      species (ROS) and DNA status (TUNEL) were analysed at 4 h. Antioxidants, except
      DHA 0.1 mm, decreased motility and kinematic parameters, but had little effect on
      viability or mitochondrial activity. Except 1 mm DHA, the antioxidants reduced
      ROS at 4 h. Moreover, NAC 1 mm, rutin and TEMPOL reduced ROS and DNA damage in
      the presence of oxidative stress. N-acetyl-cysteine, rutin 1 mm and TEMPOL
      reduced lipoperoxidation in the presence of oxidative stress. However, DHA did
      not affect lipoperoxidation. At 1 mm, DHA increased DNA damage in the absence of
      oxidative stress. Dehydroascorbic acid effects could arise from spermatozoa
      having a low capacity for reducing it to ascorbic acid, and it may be tested in
      the presence of other antioxidants or reducing power. Future research should
      focus in testing whether the inhibition of motility observed for NAC, rutin and
      TEMPOL is reversible. These antioxidants might be useful at lower temperatures
      (refrigerated storage or cryopreservation) when their protective effects could be
      advantageous.

PMID- 22372743
TI  - Ordering transitions triggered by specific binding of vesicles to protein
      decorated interfaces of thermotropic liquid crystals.
AB  - We report that specific binding of ligand-functionalized (biotinylated)
      phospholipid vesicles (diameter = 120 +/- 19 nm) to a monolayer of proteins
      (streptavidin or anti-biotin antibody) adsorbed at an interface between an
      aqueous phase and an immiscible film of a thermotropic liquid crystal (LC)
      [nematic 4'-pentyl-4-cyanobiphenyl (5CB)] triggers a continuous orientational
      ordering transition (continuous change in the tilt) in the LC. Results presented
      in this paper indicate that, following the capture of the vesicles at the LC
      interface via the specific binding interaction, phospholipids are transferred
      from the vesicles onto the LC interface to form a monolayer, reorganizing and
      partially displacing proteins from the LC interface. The dynamics of this process
      are accelerated substantially by the specific binding event relative to a protein
      decorated interface of a LC that does not bind the ligands presented by the
      vesicles. The observation of the continuous change in the ordering of the LC,
      when combined with other results presented in this paper, is significant, as it
      is consistent with the presence of suboptical domains of proteins and
      phospholipids on the LC interface. An additional significant hypothesis that
      emerges from the work reported in this paper is that the ordering transition of
      the LC is strongly influenced by the bound state of the protein adsorbed on the
      LC interface, as evidenced by the influence on the LC of (i) "crowding" of the
      protein within a monolayer formed at the LC interface and (ii) aging of the
      proteins on the LC interface. Overall, these results demonstrate that ordering
      transitions in LCs can be used to provide fundamental insights into the
      competitive adsorption of proteins and lipids at oil-water interfaces and that LC
      ordering transitions have the potential to be useful for reporting specific
      binding events involving vesicles and proteins.

PMID- 22372744
TI  - Development of fetal trabecular micro-architecture in the humerus and femur.
AB  - It is widely accepted that during postnatal development trabecular bone adapts to
      the prevailing loading environment via modelling. However, very little is known
      about the mechanisms (whether it is predominantly modelling or remodelling) or
      controls (such as whether loading influences development) of fetal bone growth.
      In order to make inferences about these factors, we assessed the pattern of fetal
      trabecular development in the humerus and femur via histomorphometric parameter
      quantification. Growth and development (between 4 and 9 months prenatal) of
      trabecular architecture (i.e. thickness, number and bone volume fraction) was
      compared across upper and lower limb bones, proximal and distal regions, and
      sexes. The data presented here indicate that during prenatal development
      trabeculae became thicker and less numerous, whilst bone volume fraction remained
      constant. This partly mimics the pattern of early postnatal development (0-2
      years) described by other researchers. Thickness was reported to increase whilst
      number reduced, but bone volume fraction decreased. This is perhaps because the
      balance of bone modelling (deposition vs. resorption) changes post partum.
      Published histological data suggest that bone deposition slows after birth, while
      resorption rates remain constant. Hence, fetal development may be characterized
      by relatively high rates of modelling and, particularly, bone deposition in
      comparison to postnatal. With respect to measures of thickness, number and bone
      volume fraction prenatal development was not bone, site, or sex specific, whilst
      postnatally these measures of architecture diverge. This is despite reported
      developmental variation in the frequency, speed and amplitude of fetal movements
      (which begin after 11 weeks and continue until birth), and probably therefore
      loading induced by muscular contractions. This may be because prenatal limb bone
      micro-architecture follows a generalised predetermined growth trajectory (or
      genetic blueprint), as appears to be the case for gross distribution of
      trabecular tissue.

PMID- 22372745
TI  - Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria
      as the "second human genome".
AB  - It has been found that the composition of intestinal microbiota can indicate the
      risk of disease to each individual. The concepts of biodynamics as used by the
      Benziger Winery in California, which treats every part of an agricultural
      environment as a living, breathing entity, can be usefully used in the
      construction of a system for cancer prevention, which seeks to use the
      relationship of coexistence (symbiosis) shared between people and intestinal
      symbiosis, that is, microbiota. Changes in the incidence rate of cancer among
      Japanese emigrants to Hawaii demonstrate the effect of the changes in the living
      environment. This leads to the hypothesis that an intake of soy-derived food
      products and the metabolization of the isoflavones they contain by intestinal
      microbiota is one of the factors for the significant difference in the incidence
      rate of prostate cancer among Asian and European/North American populations. It
      is further hypothesized that isoflavones, particularly equol, are a key factor in
      the difference in incidence rate between Asia and the West. It is suggested that
      not having equol converting bacteria in the intestine (non-equol producers) can
      be a risk factor for prostate cancer and that one direction for future research
      will be to examine the possibility of improving the intestinal environment to
      enable equol production.

PMID- 22372746
TI  - Nanosystem self-assembly pathways discovered via all-atom multiscale analysis.
AB  - We consider the self-assembly of composite structures from a group of
      nanocomponents, each consisting of particles within an N-atom system. Self
      assembly pathways and rates for nanocomposites are derived via a multiscale
      analysis of the classical Liouville equation. From a reduced statistical
      framework, rigorous stochastic equations for population levels of beginning,
      intermediate, and final aggregates are also derived. It is shown that the
      definition of an assembly type is a self-consistency criterion that must strike a
      balance between precision and the need for population levels to be slowly varying
      relative to the time scale of atomic motion. The deductive multiscale approach is
      complemented by a qualitative notion of multicomponent association and the
      ensemble of exact atomic-level configurations consistent with them. In processes
      such as viral self-assembly from proteins and RNA or DNA, there are many possible
      intermediates, so that it is usually difficult to predict the most efficient
      assembly pathway. However, in the current study, rates of assembly of each
      possible intermediate can be predicted. This avoids the need, as in a
      phenomenological approach, for recalibration with each new application. The
      method accounts for the feedback across scales in space and time that is
      fundamental to nanosystem self-assembly. The theory has applications to
      bionanostructures, geomaterials, engineered composites, and nanocapsule
      therapeutic delivery systems.

PMID- 22372747
TI  - New substrates and enzyme assays for the detection of mucopolysaccharidosis III
      (Sanfilippo Syndrome) types A, B, C, and D by tandem mass spectrometry.
AB  - The clinical phenotype of Sanfilippo Syndrome is caused by one of four enzyme
      deficiencies that are associated with a defect in mucopolysaccharide metabolism.
      The four subtypes (A, B, C, and D) are each caused by an enzyme deficiency
      involved in the degradation of heparan sulfate. We have developed a highly
      efficient synthesis of the substrates and internal standards required for the
      enzymatic assay of each of the four enzymes. The synthesis of the substrates
      involves chemical modification of a common intermediate. The substrates and
      internal standards allow the measurement of the enzymes relevant to heparan N
      sulfatase (type A); N-acetyl-alpha-glucosaminidase (type B); acetyl-CoA:alpha
      glucosamide N-acetyltransferase (type C); and N-acetylglucosamine 6-sulfatase
      (type D). The internal standards are similar to the substrates and allow for the
      accurate quantification of the enzyme assays using tandem mass spectrometry. The
      synthetic substrates incorporate a coumarin moiety and can also be used in
      fluorometric enzyme assays. We confirm that all four substrates can detect the
      appropriate Sanfilippo Syndrome in fibroblast lysates, and the measured enzyme
      activities are distinctly lower by a factor of 10 when compared to fibroblast
      lysates from unaffected persons.

PMID- 22372748
TI  - Skull typology of Byzantine dogs from the Theodosius Harbour at Yenikapi,
      Istanbul.
AB  - This study presents the results of craniometric analysis of 500 Byzantine Era dog
      skulls from the ancient site of the Theodosius Harbour in Istanbul (modern
      Yenikapi neighbourhood). To determine the typology of the skulls, up to 36
      craniometric measurements were taken on each specimen. Fourteen indices and
      ratios were calculated from the measurements. Results show that the majority
      (97%) of the Byzantine dogs from the Yenikapi excavations were of mesocephalic
      type. Only 15 of the analysed skulls (3%) were of the dolichocephalic type. Only
      one dog skeleton has been recovered in situ during the excavations; analysis
      indicates that this individual belonged to a mesocephalic type dog.
      Brachycephalic dog skulls were absent in the samples studied from Byzantine
      Yenikapi. The results give important insight in continuities and discontinuities
      in dog-breeding traditions from the Roman to the Byzantine Eras, and between the
      West and the East during Medieval times.

PMID- 22372749
TI  - Good guys from a shady family.

PMID- 22372750
TI  - Health care experiences prior to suicide and self-inflicted injury, active
      component, U.S. Armed Forces, 2001-2010.
AB  - Suicide is a leading cause of deaths of U.S. service members. Medical care
      providers may play a role in suicide prevention. We summarized the outpatient
      experiences of service members prior to suicide or self-inflicted injury and
      compared them with service members without suicidal behavior. During 2001-2010,
      45 percent of individuals who completed suicide and 75 percent of those who
      injured themselves had outpatient encounters within 30 days prior to suicide/self
      harm. Primary care was the most frequently visited clinical service prior to
      suicide/self-harm. As compared to their counterparts, service members with
      suicidal behavior had especially excessive outpatient visit rates within, but not
      prior to, 60 days of their deaths/injuries. The finding suggests that there may
      be one or more "triggering" events that lead to care-seeking. These results may
      help identify individuals that should be screened for suicide risk.

PMID- 22372751
TI  - Relations between suicide and traumatic brain injury, psychiatric diagnoses, and
      relationship problems, active component, U.S. Armed Forces, 2001-2009.
AB  - This retrospective case-control study of members of the active component of the
      U.S. Armed Forces compared those who died from suicide to controls matched by
      service, gender, race, age, date of entry into the active component, and years of
      service. Th e surveillance period was 2001 to 2009. The groups were compared with
      respect to numbers of deployments and documented diagnoses of traumatic brain
      injury (TBI), mood disorders, alcohol dependence, post-traumatic stress disorder
      (PTSD), partner relationship problems, and family circumstance problems. Cases
      and controls were similar regarding frequencies and types of TBIs and numbers of
      deployments. In multivariate analyses, increased odds of suicide were associated
      with mood disorders, partner relationship problems, and family circumstance
      problems, but not with mild TBI, alcohol dependence, or PTSD. A separate analysis
      revealed that psychiatric comorbidities increased odds of suicide. Limitations
      are discussed, including the possibility that some controls with mild TBIs may
      have died from suicide after their military service.

PMID- 22372752
TI  - Outpatient encounters associated with diagnostic codes for migraine and other
      types of headaches, active component service members, 1998-2010.
AB  - This analysis examines incidence rates, prevalences, and outpatient encounters
      for migraine and other headache syndromes among active component members of the
      U.S. Armed Forces from 1998 through 2010. For both migraine and other headache
      syndromes, incidence rates, prevalences, and rates of outpatient encounters
      increased during the period. In 2010, 3.9 percent of male service members and
      11.3 percent of females had at least one outpatient encounter for an episode of
      headache; rates were higher among females than males. Among service members ever
      diagnosed with migraine, 3 percent of men and 6 percent of women had more than 10
      encounters for migraine; for other headache syndromes, the respective percentages
      were less than 1 percent. The introduction of new ICD-9 codes during the period
      had little effect on the coding practices for migraine, but did modestly affect
      the coding practices for other headache syndromes.

PMID- 22372753
TI  - Medical evacuations from Operation Iraqi Freedom/Operation New Dawn, active and
      reserve components, U.S. Armed Forces, 2003-2011.
AB  - From January 2003 to December 2011, over 50,000 service members were medically
      evacuated from the Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) theater
      of combat operations to a medical treatment facility outside of theater. During
      the period, the numbers and underlying causes of medical evacuations sharply
      varied in relation to the numbers of deployed service members and the natures of
      ongoing military operations. There were nearly five times as many medical
      evacuations for disease and non-battle injuries than for battle-related
      conditions. The majority of medical evacuations (87%) occurred among males; the
      major causes of medical evacuations differed among male and female deployers.
      Based on these findings, force health protection policies and practices should be
      tailored to the characteristics of the deployed force and the nature of the
      military operation.

PMID- 22372754
TI  - Surveillance snapshot: Medical evacuations from Operation Enduring Freedom (OEF),
      active and reserve components, U.S. Armed Forces, October 2001-December 2011.

PMID- 22372755
TI  - Surveillance snapshot: Recurrent medical encounters associated with alcohol abuse
      related diagnostic codes, active component, U.S. Armed Forces, 2001-2010.

PMID- 22372756
TI  - Regular and platform switching: bone stress analysis varying implant type.
AB  - PURPOSE: This study aimed to evaluate stress distribution on peri-implant bone
      simulating the influence of platform switching in external and internal hexagon
      implants using three-dimensional finite element analysis. MATERIALS AND METHODS:
      Four mathematical models of a central incisor supported by an implant were
      created: External Regular model (ER) with 5.0 mm * 11.5 mm external hexagon
      implant and 5.0 mm abutment (0% abutment shifting), Internal Regular model (IR)
      with 4.5 mm * 11.5 mm internal hexagon implant and 4.5 mm abutment (0% abutment
      shifting), External Switching model (ES) with 5.0 mm * 11.5 mm external hexagon
      implant and 4.1 mm abutment (18% abutment shifting), and Internal Switching model
      (IS) with 4.5 mm * 11.5 mm internal hexagon implant and 3.8 mm abutment (15%
      abutment shifting). The models were created by SolidWorks software. The numerical
      analysis was performed using ANSYS Workbench. Oblique forces (100 N) were applied
      to the palatal surface of the central incisor. The maximum (sigma(max)) and
      minimum (sigma(min)) principal stress, equivalent von Mises stress (sigma(vM)),
      and maximum principal elastic strain (epsilon(max)) values were evaluated for the
      cortical and trabecular bone. RESULTS: For cortical bone, the highest stress
      values (sigma(max) and sigma(vm) ) (MPa) were observed in IR (87.4 and 82.3),
      followed by IS (83.3 and 72.4), ER (82 and 65.1), and ES (56.7 and 51.6). For
      epsilon(max), IR showed the highest stress (5.46e-003), followed by IS (5.23e
      003), ER (5.22e-003), and ES (3.67e-003). For the trabecular bone, the highest
      stress values (sigma(max)) (MPa) were observed in ER (12.5), followed by IS (12),
      ES (11.9), and IR (4.95). For sigma(vM), the highest stress values (MPa) were
      observed in IS (9.65), followed by ER (9.3), ES (8.61), and IR (5.62). For
      epsilon(max) , ER showed the highest stress (5.5e-003), followed by ES (5.43e
      003), IS (3.75e-003), and IR (3.15e-003). CONCLUSION: The influence of platform
      switching was more evident for cortical bone than for trabecular bone, mainly for
      the external hexagon implants. In addition, the external hexagon implants showed
      less stress concentration in the regular and switching platforms in comparison to
      the internal hexagon implants.

PMID- 22372757
TI  - Asymmetry of familial exudative vitreoretinopathy.
AB  - A 2-month-old male infant presented with unilateral leukocoria suspected to be
      retinoblastoma. Fundus examination and fluorescein angiography confirmed the
      diagnosis of bilateral familial exudative vitreoretinopathy with markedly
      asymmetric presentation (Stage 3/Type 5 in the right eye and Stage 2/Type 3 in
      the left eye).

PMID- 22372758
TI  - Thrombotic thrombocytopenic purpura.
AB  - A 34-year old primipara was admitted to hospital with dichorionic-diamniotic
      twins in 26+3 weeks of gestation. In suspicion of HELLP-syndrome, caesarean
      section was performed at 27+4 weeks of gestation, because of platelet count was
      reduced to 44000/ul. A re-laparotomy had to be performed because of intra
      abdominal bleedings. The patient was given seven packed thrombocytes and five
      packed erythrocytes. The patient complained about blurred vision. The right
      corner of the mouth was slightly depressed in terms of a facial nerve paresis.
      Further platelet counts were about 50000/ul. Haemoglobin: 7.8 mg/l. D-Dimer: 1066
      mg/l. LDH was elevated to 1610 U/l, reticulocytes were elevated to 13.19% and
      haptoglobin was reduced to <0.08 g/l. The Coombs' test was negative. The ADAMTS
      13 test showed a reduced activity. Hereby, the diagnoses of thrombotic
      thrombocytopenic purpura was confirmed. Plasma exchange is the most effective
      option; application of platelet concentrate should be avoided, because of
      worsening microangiopathy and subsequent neurological situation. After the
      patient has received plasma exchange, platelet count normalized. An ophthalmic
      examination showed a dysfunction in choroid perfusion as a cause for the blurred
      vision. After discharge regular lab tests were planned, but no further treatment
      was necessary at that point of time. The premature twins survived after
      ventricular haemorrhage, severe sepsis, bronchopulmonary dysplasia and other
      complications of neonates.

PMID- 22372760
TI  - Synthesis and electronic, photophysical, and electrochemical properties of a
      series of thienylcarbazoles.
AB  - A series of thienylcarbazoles were synthesized by Suzuki-Miyaura and Ullmann
      coupling reactions. In these compounds, the 2-thienyl or 2,2'-bithiophen-5-yl
      group is connected at the N-, 1,8-, 3,6-, 2,7-, 2,7,N-, or 1,8,N-positions of the
      carbazole ring. The effects of structural variations on their electronic,
      photophysical, and electrochemical properties were explored by UV-vis and
      fluorescence spectroscopies, cyclic voltammetry (CV), and DFT calculations in
      evaluation of their potential as material components. The thienyl substituents at
      the 2,7-positions in 4, 5, and 10 are responsible for a high degree of pi
      conjugation and strong emission with fluorescence quantum yields up to 0.61. The
      CV on a series of thienylcarbazoles revealed a good electron-donating ability of
      3,6-substituted carbazoles 3 and 9. The number of thiophene units was found to
      affect the extent of pi-conjugation, the resulting HOMO-LUMO gaps, and
      fluorescence efficiency. The crystal structures of 5 and 9 were also disclosed.

PMID- 22372759
TI  - Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients.
AB  - The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory
      confirmed Dutch cases were examined. An episode lasted a median of 7.5 days of
      which 2 days included fever. Respiratory symptoms resolved slowly, while systemic
      symptoms peaked early in the episode and disappeared quickly. Severity of each
      symptom was rated highest in the first few days. Furthermore, diarrhoea was
      negatively associated with viral load, but not with faecal excretion of influenza
      virus. Cases with comorbidities appeared to have higher viral loads than the
      cases without, suggesting a less effective immune response. These results
      complement information obtained through traditional surveillance.

PMID- 22372761
TI  - Have changes in ECMO technology impacted outcomes in adult patients developing
      postcardiotomy cardiogenic shock?
AB  - Extracorporeal membrane oxygenation (ECMO) technology has undergone several
      advancements over the last decade. We sought to compare current ECMO technology
      to older ones to determine how these technological improvements have impacted
      outcomes in patients suffering from postcardiotomy cardiogenic shock (PCS).
      Between 2005 and 2010, 49 patients received ECMO as support for PCS following
      elective cardiac surgery. Patients were divided into three groups. Group 1 (Gp 1,
      n = 11) patients received a Biomedicus pump with an Affinity oxygenator, Group 2
      (Gp 2, n = 11) patients received a Biomedicus pump with a Quadrox D oxygenator,
      and Group 3 (Gp 3, n = 27) patients received a Rotaflow pump with a Quadrox D
      oxygenator. Groups were compared with regards to adverse events and ability to
      wean. Adverse event analysis showed no statistically significant difference
      between groups in incidence of stroke (p = 0.08), renal failure (p = 0.88), or
      bleeding requiring reexploration (p = 0.10). Changes in technology did little to
      improve weaning rates from ECMO (Gp 1 = 63.6%, Gp 2 = 45.5%, and Gp 3 = 55.6%).
      Similar trends were detected in hospital survival (Gp 1 = 27.3%, Gp 2 = 27.3%,
      and Gp 3 = 33.3%). Technology did impact oxygenator durability with Gp 1
      requiring seven (63.6%) oxygenator exchanges compared to zero (0.0%) in Gp 2 and
      two (7.4%) in Gp 1. While advancements in ECMO technology have resulted in
      improved oxygenator durability, outcomes in patients requiring such support for
      PCS continue to be poor.

PMID- 22372762
TI  - Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary
      bladder.
AB  - Study Type - Prognosis (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Apoptotic pathways are important in
      carcinogenesis. Many studies, involving small numbers of patients, have found an
      association between one or two apoptotic markers and some of the pathological
      features of squamous cell carcinoma (SCC). This study included a large number of
      patients who had undergone radical cystectomy (RC) for SCC with long-term follow
      up, allowing us to study biomarker alterations and their prognostic role. This is
      the first study on the prognostic role of a panel of apoptotic-related markers in
      SCC of the urinary bladder, introducing the novel concept of a prognostic marker
      score based on the number of altered markers. We found that apoptotic markers can
      improve prediction of oncological outcomes after RC for SCC and might potentially
      help in patient selection for adjunct therapies. OBJECTIVE: To evaluate the
      association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with
      pathological features and clinical outcomes in patients with squamous cell
      carcinoma (SCC) of the urinary bladder. METHODS: Immunohistochemistry for CC-3,
      Bax, COX-2, and p53 was performed on tissue microarray sections of radical
      cystectomy specimens with pure SCC from 1997 to 2003. The relationship between
      the expression of these markers and pathological features was assessed. * A
      prognostic marker score (PS) was defined as favourable if <=2 biomarkers were
      altered and unfavourable if >2 biomarkers were altered and the association of the
      PS with oncological outcomes was examined. RESULTS: The study included 151
      patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC
      was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. *
      Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients.
      Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and
      lymphovascular invasion was found in 16% of patients. * Median follow-up was 63.2
      months. * Advanced stage was associated with COX-2, p53 and CC-3 alterations and
      high grade was associated with COX-2 alterations (P < 0.05). The total number of
      altered markers and unfavourable PS were associated with both disease recurrence
      and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05).
      Unfavourable PS was an independent predictor of disease recurrence (hazard ratio
      [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder
      cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in
      multivariable Cox regression analysis. CONCLUSION: Markers of apoptosis pathways
      may play an important role in the prognosis of SCC of the bladder. An increased
      number of altered markers and an unfavourable PS may identify patients who might
      benefit from multimodal therapies.

PMID- 22372763
TI  - Toxicogenomic responses of the model organism Caenorhabditis elegans to gold
      nanoparticles.
AB  - We used Au nanoparticles (Au-NPs) as a model for studying particle-specific
      effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic
      responses in a model soil organism,  Caenorhabditis elegans . Global genome
      expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC(10)
      level (5.9 mg.L(-1)) revealed significant differential expression of 797 genes.
      The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4)
      were confirmed independently with qRT-PCR. Seven common biological pathways
      associated with 38 of these genes were identified. Up-regulation of 26 pqn/abu
      genes from noncanonical unfolded protein response (UPR) pathway and molecular
      chaperones (hsp-16.1, hsp-70, hsp-3, and hsp-4) were observed and are likely
      indicative of endoplasmic reticulum stress. Significant increase in sensitivity
      to Au-NPs in a mutant from noncanonical UPR (pqn-5) suggests possible involvement
      of the genes from this pathway in a protective mechanism against Au-NPs.
      Significant responses to Au-NPs in endocytosis mutants (chc-1 and rme-2) provide
      evidence for endocytosis pathway being induced by Au-NPs. These results
      demonstrate that Au-NPs are bioavailable and cause adverse effects to  C. elegans
      by activating both general and specific biological pathways. The experiments
      with mutants further support involvement of several of these pathways in Au-NP
      toxicity and/or detoxification.

PMID- 22372764
TI  - Concurrent care for the medically complex child: lessons of implementation.
AB  - After years of the palliative care community calling for more open access to
      hospice services, pediatric patients are now eligible to receive simultaneous
      hospice services and disease-directed therapy. We report on five types of
      challenges that our team has experienced when implementing concurrent care,
      illustrated through case studies of three medically complex pediatric patients.

PMID- 22372766
TI  - Response of boar sperm to the treatment with cholesterol-loaded cyclodextrins
      added prior to cryopreservation.
AB  - Cryopreserved boar sperm is not used extensively for artificial insemination,
      owing to the poor fertility rates of the sperm after freezing and thawing. The
      sperm membrane is damaged as the cells are cooled from body temperature to 5
      degrees C (cold shock), as well as during the freeze-thaw process. Increasing the
      cholesterol content of boar sperm membranes could help them survive
      cryopreservation, similar to sperm from other species that are cold shock
      sensitive. The aim of this study was to determine the optimal cholesterol-loaded
      cyclodextrin (CLC) concentration to use for boar sperm cryopreservation, and the
      influence of CLCs on the cryosurvival of sperm from boars classified as good or
      poor freezers. Treating boar sperm with 1 mg of CLC/120 * 10(6) sperm slightly
      improved (p < 0.05) the percentage of viable sperm after freezing-thawing. On the
      other hand, sperm, from both good and poor freezers, responded similarly to CLC
      treatment. Nevertheless, additional studies will be needed to study the effect of
      this treatment on other parameters of sperm quality.

PMID- 22372765
TI  - Investigation and identification of protein gamma-glutamyl carboxylation sites.
AB  - BACKGROUND: Carboxylation is a modification of glutamate (Glu) residues which
      occurs post-translation that is catalyzed by gamma-glutamyl carboxylase in the
      lumen of the endoplasmic reticulum. Vitamin K is a critical co-factor in the post
      translational conversion of Glu residues to gamma-carboxyglutamate (Gla)
      residues. It has been shown that the process of carboxylation is involved in the
      blood clotting cascade, bone growth, and extraosseous calcification. However,
      studies in this field have been limited by the difficulty of experimentally
      studying substrate site specificity in gamma-glutamyl carboxylation. In silico
      investigations have the potential for characterizing carboxylated sites before
      experiments are carried out. RESULTS: Because of the importance of gamma-glutamyl
      carboxylation in biological mechanisms, this study investigates the substrate
      site specificity in carboxylation sites. It considers not only the composition of
      amino acids that surround carboxylation sites, but also the structural
      characteristics of these sites, including secondary structure and solvent
      accessible surface area (ASA). The explored features are used to establish a
      predictive model for differentiating between carboxylation sites and non
      carboxylation sites. A support vector machine (SVM) is employed to establish a
      predictive model with various features. A five-fold cross-validation evaluation
      reveals that the SVM model, trained with the combined features of positional
      weighted matrix (PWM), amino acid composition (AAC), and ASA, yields the highest
      accuracy (0.892). Furthermore, an independent testing set is constructed to
      evaluate whether the predictive model is over-fitted to the training set.
      CONCLUSIONS: Independent testing data that did not undergo the cross-validation
      process shows that the proposed model can differentiate between carboxylation
      sites and non-carboxylation sites. This investigation is the first to study
      carboxylation sites and to develop a system for identifying them. The proposed
      method is a practical means of preliminary analysis and greatly diminishes the
      total number of potential carboxylation sites requiring further experimental
      confirmation.

PMID- 22372767
TI  - A genetic approach to the species problem in wild potato.
AB  - Wild potatoes are native to the Americas, where they present very wide
      geographical and ecological distribution. Most are diploid, obligate out-crossers
      due to a multiallelic gametophytic self-incompatibility (S) locus that prevents
      self-fertilisation and crossing between individuals carrying identical S-alleles.
      They have two alternative modes of reproduction: sexual (by seeds) and asexual
      (by stolons and tubers), which provide, respectively, for genetic flexibility in
      changing environments and high fitness of adapted genotypes under stable
      conditions. Since the early twentieth century, their taxonomic classification has
      been mostly based on morphological phenotypes (Taxonomic Species Concept). More
      recently, attempts have been made to establish phylogenetic relationships,
      applying molecular tools in samples of populations (accessions) with a previously
      assigned specific category. However, neither the reproductive biology and
      breeding relations among spontaneous populations nor the morphological and
      genetic variability expected in obligate allogamous populations are considered
      when the taxonomic species concept is applied. In nature, wild potato populations
      are isolated through external and internal hybridisation barriers; the latter,
      which are genetically determined, can be either pre-zygotic (pollen-pistil
      incompatibility) or post-zygotic (abortion of embryo, endosperm or both tissues,
      sterility, and hybrid weakness and breakdown in segregating generations). The
      internal barriers, however, can be incomplete, providing opportunities for
      hybridisation and introgression within and between populations and ploidy levels
      in areas of overlap. The widespread occurrence of spontaneous hybrids in nature
      was recognised in the mid-twentieth century. Using genetic approaches, results
      have been obtained that provide strong support to the assertion that populations
      are at different stages of genetic divergence and are not at the end of the
      evolutionary process, as presupposed by the Taxonomic Species Concept.
      Furthermore, since wild potatoes have uniparental and biparental overlapping
      generations, the Biological Species Concept - developed for sexually reproducing
      biparental organisms - cannot be applied to them. In this paper, morphological,
      genetic, molecular and taxonomic studies in wild potato are reviewed, considering
      the genetic consequences of their reproductive biology, in an attempt to shed
      light on the species problem, because of its relevance in germplasm conservation
      and breeding.

PMID- 22372768
TI  - Bottom-up assembly of colloidal gold and silver nanostructures for designable
      plasmonic structures and metamaterials.
AB  - We report on bottom-up assembly routes for fabricating plasmonic structures and
      metamaterials composed of colloidal gold and silver nanostructures, such as
      nanoparticles ("metatoms") and shape-controlled nanocrystals. Owing to their well
      controlled sizes/shapes, facile surface functionalization, and excellent
      plasmonic properties in the visible and near-infrared regions, these
      nanoparticles and nanocrystals are excellent building blocks of plasmonic
      structures and metamaterials for optical applications. Recently, we have utilized
      two kinds of bottom-up techniques (i.e., multiple-probe-based nanomanipulation
      and layer-by-layer self-assembly) to fabricate strongly coupled plasmonic dimers,
      one-dimensional (1D) chains, and large-scale two-dimensional/three-dimensional
      (2D/3D) nanoparticle supercrystals. These coupled nanoparticle/nanocrystal
      assemblies exhibit unique and tunable plasmonic properties, depending on the
      material composition, size/shape, intergap distance, the number of composing
      nanoparticles/nanocrystals (1D chains), and the nanoparticle layer number in the
      case of 3D nanoparticle supercrystals. By studying these coupled
      nanoparticle/nanocrystal assemblies, the fundamental plasmonic metamaterial
      effects could be investigated in detail under well-prepared and previously
      unexplored experimental settings.

PMID- 22372770
TI  - Design, evaluation, and comparison of ghrelin receptor agonists and inverse
      agonists as suitable radiotracers for PET imaging.
AB  - Ghrelin agonist and inverse agonist radiotracers, suitable for positron emission
      tomography (PET), were developed to study the behavior of ghrelin receptor
      ligands in vivo and for further design of druggable peptides. The target peptides
      were synthesized on solid support and conjugated to the bifunctional chelator
      1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), which is known
      to form a stable complex with Ga(3+). Complexation with (68)Ga could be achieved
      under mild conditions and led to radiotracers with high radiochemical purity and
      specific activity. The biological activity of the radiotracers was evaluated in
      vitro by an inositol phosphate turnover assay. Pharmacokinetic profile and
      metabolic stability of the (68)Ga-NODAGA-radiotracers were investigated by small
      animal PET in rodent. Ghrelin derived agonists presented very high kidney
      accumulation, negligible tissue distribution, fast blood clearance, and poor
      stability in blood. Contrarily, the inverse agonist radiotracer exhibited very
      high stability in blood, large diffusion in tissues, reasonable kidney and liver
      metabolism, and slow blood clearance. This pharmacokinetic profile makes the
      ghrelin inverse agonist motif KwFwLL-CONH(2) suitable for further development of
      radiotracers and a promising lead to design peptide-based therapeutics against
      obesity.

PMID- 22372769
TI  - Dynamic nuclear polarization with a water-soluble rigid biradical.
AB  - A new biradical polarizing agent, bTbtk-py, for dynamic nuclear polarization
      (DNP) experiments in aqueous media is reported. The synthesis is discussed in
      light of the requirements of the optimum, theoretical, biradical system. To date,
      the DNP NMR signal enhancement resulting from bTbtk-py is the largest of any
      biradical in the ideal glycerol/water solvent matrix, epsilon = 230. EPR and X
      ray crystallography are used to characterize the molecule and suggest approaches
      for further optimizing the biradical distance and relative orientation.

PMID- 22372771
TI  - Obesity and hypertension: a common coexistence.

PMID- 22372772
TI  - Techniques for self-measurement of blood pressure: limitations and needs for
      future research.
AB  - Self blood pressure measurement (SBPM) improves the overall management of
      hypertension provided it is implemented with methodologic care. This concerns
      especially the accuracy and technical requirements of blood pressure (BP)
      measuring devices that should be validated according to internationally accepted
      protocols. The use of memory-equipped automatic home monitors is strongly
      recommended because they reduce observer bias, avoid patients' misreporting, and
      allow fully automatic analysis by software. For current use, simple software
      should be worked out that allow for analysis of readings in an objective manner.
      Miscuffing is also a frequent source of measurement error in obese arms when
      oscillometric devices are used. Modern automatic devices can overcome this
      problem because of special software algorithms that can provide accurate
      measurements over a wide range of arm circumferences when coupled with a single
      cuff of standard dimensions. Tronco-conical-shaped cuffs are a key component of
      this instrumentation because they better fit on large conical arms frequently
      present in obese individuals. Semi-rigid cuffs should be increasingly used
      because they ensure that the proper amount of tension is applied without the
      intervention of the user. Continuous technology improvement of instrumentation
      for SBPM can be achieved through close cooperation between manufacturers and
      validation centers.

PMID- 22372773
TI  - The relationship of peripheral arterial disease and metabolic syndrome prevalence
      in asymptomatic US adults 40 years and older: results from the National Health
      and Nutrition Examination Survey (1999-2004).
AB  - Peripheral arterial disease (PAD) is a subclinical marker of coronary artery
      disease and identifies asymptomatic individuals at high risk for cardiovascular
      disease (CVD) events. The metabolic syndrome (MetS) is a constellation of
      clinical factors that increases the risk of developing diabetes and CVD. The
      authors' objectives were to estimate the prevalence of MetS in patients with PAD
      and to determine the prevalence of PAD in the population of asymptomatic US
      adults 40 years and older with MetS. The authors analyzed data from 3 National
      Health and Nutrition Examination Surveys (NHANES, 1999-2004). Prevalence of MetS
      as defined by the Third Report of the Adult Treatment Panel criteria and
      prevalence of associated cardiac risk factors were determined in 5376
      asymptomatic participants 40 years and older. Presence of PAD was defined as
      ankle-brachial index <0.9. Estimates were weighted with the sample weights
      accounting for the unequal selection probability of complex NHANES sampling and
      over sampling of selected population subgroups. Prevalence of PAD in asymptomatic
      US adults 40 years and older was 4.2%. PAD prevalence in persons with MetS was
      7.0% compared with 3.3% in persons without MetS. A total of 38% of the population
      with PAD also had MetS. High rates of abdominal obesity, hypertension,
      hyperglycemia, and low high-density lipoprotein cholesterol are significant
      contributors to both MetS and PAD. Persons with MetS have twice the risk of
      having PAD. Of persons with PAD, almost 40% have MetS. The presence of either PAD
      or MetS should warrant screening for both conditions so that risk stratification
      and management of risk factors may be performed.

PMID- 22372774
TI  - Long-term efficacy and safety of triple-combination therapy with olmesartan
      medoxomil and amlodipine besylate and hydrochlorothiazide for hypertension.
AB  - J Clin Hypertens (Greenwich). 2012;14:149-157. (c)2012 Wiley Periodicals, Inc.
      Most patients with hypertension require combination therapy in order to achieve
      blood pressure (BP) goals. This 40-week open-label extension of the 12-week
      double-blind Triple Therapy With Olmesartan Medoxomil, Amlodipine, and
      Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) evaluated the
      efficacy and safety of triple-combination treatments with olmesartan medoxomil,
      amlodipine besylate, and hydrochlorothiazide (OM/AML/HCTZ) in 2112 participants
      with moderate to severe hypertension. Following 2 weeks of initial treatment with
      OM 40/AML 5/HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM
      40/AML 5/HCTZ 25 mg or OM 40/AML 10/HCTZ 12.5 mg on a randomized basis. At week
      16, participants who did not achieve BP goal were further titrated to OM 40/AML
      10/HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP
      goal and the mean BP decreased from 168.6/100.7 mm Hg (baseline BP at
      randomization) to 125.0 to 136.8 mm Hg/77.8 to 82.5 mm Hg, depending on
      treatment. Long-term treatment with OM/AML/HCTZ was well tolerated and effective
      with no new safety concerns.

PMID- 22372775
TI  - Evaluations of hospitalizations associated with thiazide-associated hyponatremia.
AB  - The prevalence of hypertension in the United States has grown dramatically in
      recent years. Thiazide diuretics have played a major role in the rising rate of
      blood pressure (BP) control. Accompanying this has been the appearance of adverse
      drug events, including hospitalizations associated with thiazide-associated
      hyponatremia (HTAH). Hyponatremia is a common yet often overlooked side effect of
      this drug class. Identification of HTAH risk factors may aid in creating
      strategies to prevent hospitalizations. This is a retrospective, case-controlled
      study of 10,805 patients (1802 cases, 9003 controls) examining HTAH risk factors
      within a group-model integrated-care organization. Multivariate analysis revealed
      that age (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.58-1.93),
      angiotensin-converting enzyme (ACE) inhibitor use (OR, 1.53; 95% CI, 1.16-2.00),
      and hypokalemia (OR, 40.94; 95% CI, 26.46-66.33) were most associated with HTAH.
      Urinary tract infection (UTI), type 2 diabetes, hyperlipidemia, and
      gastroesophageal reflux disease (GERD) were also found to be HTAH risk factors.
      Potassium supplements (OR, 0.60; 95% CI, 0.44-0.83) and weight (OR, 0.91; 95% CI,
      0.88-0.93) had protective effects. A predictive model was developed to determine
      overall HTAH risk given the presence of individual risk factors. Age, weight,
      hypokalemia, GERD, type 2 diabetes, UTI, and ACE inhibitor use independently
      correlated with an increased risk of HTAH. This model may be applied in clinical
      practice to guide thiazide prescribing.

PMID- 22372776
TI  - Within-visit variability of blood pressure and all-cause and cardiovascular
      mortality among US adults.
AB  - The association between within-visit variability of systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) and all-cause and cardiovascular (CVD)
      mortality was examined using the Third National Health and Nutrition Survey
      (n=15,317). Three SBP and DBP readings were taken by physicians during a single
      medical evaluation. Within-visit variability for each participant was defined
      using the standard deviation of SBP and DBP across these measurements. Mortality
      was assessed over 14 years (n=3848 and n=1684 deaths from all causes and CVD,
      respectively). After age, sex, and race-ethnicity adjustment, the hazard ratios
      (95% confidence intervals) for all-cause mortality associated with the 4 highest
      quintiles of within-visit standard deviation of SBP (2.00-2.99 mm Hg, 3.00-3.99
      mm Hg, 4.00-5.29 mm Hg, and >=5.30 mm Hg) compared with participants in the
      lowest quintile of within-visit standard deviation of SBP (<2.0 mm Hg) were 1.04
      (0.87-1.26), 1.09 (0.92-1.29), 1.06 (0.88-1.28), and 1.13 (0.95-1.33),
      respectively (P=.136). The analogous hazard ratios for CVD mortality were 0.95
      (0.69-1.32), 0.96 (0.67-1.36), 0.95 (0.74-1.23), and 1.04 (0.80-1.35),
      respectively (P=.566). No association with mortality was present after further
      adjustment and when modeling within-visit standard deviation of SBP as a
      continuous variable. Standard deviation of DBP was not associated with mortality.

PMID- 22372777
TI  - Regular use of a home blood pressure monitor by hypertensive adults-
      HealthStyles, 2005 and 2008.
AB  - The authors analyzed HealthStyles surveys 2005 and 2008 combined to assess the
      prevalence of regular home blood pressure monitor (HBPM) use among hypertensive
      adults. All data were self-reported. The authors calculated odds ratios (ORs) of
      regular HBPM use and relative percent change (RPC) in the use of HBPM between the
      2 survey years. There were 3739 (32.6%) hypertensives in the 2 survey years
      combined. Based on the self-reported data, the proportion of hypertensives who
      regularly used an HBPM was 43.2%. Male sex, age, race/ethnicity, household
      income, and education were all associated with differences in the prevalence of
      regular HBPM use. Patients 65 years and older (OR, 2.38; 95% confidence interval
      [CI], 1.49-3.81) were significantly more likely to be regular HBPM users than
      those 18 to 34 years. Non-Hispanic blacks were significantly less likely (OR,
      0.69; 95% CI, 0.55-0.86) to be regular HBPM users than non-Hispanic whites. From
      2005 to 2008, the RPC in regular HBPM use was 14.2% (from 40.1% to 45.8%); the
      largest RPCs were for the 3 youngest age groups, men, non-Hispanic blacks, and
      those with a household income of $40,000 to 59,900. Because HBPM has been
      demonstrated to aid in hypertension control, health care professionals should
      promote its use especially among hypertensives who are younger, non-Hispanic
      blacks, Hispanics, or with a lower income.

PMID- 22372778
TI  - Creating community collaboration to improve the care of patients with high blood
      pressure: lessons from Rochester, New York.
AB  - Over the past two years, the business community of Monroe County, which includes
      Rochester, New York, has been engaging in a collaborative to improve outcomes for
      people with high blood pressure. As the employers examined the costs of care in
      the community, they recognized two important factors. First, the costs of care
      for the uninsured, the underinsured, and the Medicare population influence the
      business community's cost of care. Second, trying to redesign care just for their
      employees alone was not effective. This project is unique in that the stimulus
      and funding for community-wide action comes from the business community. They saw
      beyond the often unsuccessful short-term cost reduction programs and joined with
      a community-focused organization, the Finger Lakes Health Systems Agency, to
      construct a multi-year, multi-faceted intervention designed to encourage practice
      redesign and an invigorated community commitment to partnership and
      accountability. This report describes the process to date and hopefully will
      stimulate conversations about mechanisms to encourage similar collaboration
      within other communities.

PMID- 22372779
TI  - The Rheos Pivotol trial evaluating baroreflex activation therapy fails to meet
      efficacy and safety end points in resistant hypertension: back to the drawing
      board.

PMID- 22372780
TI  - Successful single-sided renal denervation approach in a patient with stenosis of
      an accessory renal artery.

PMID- 22372781
TI  - Aliskiren: a potential antiarrhythmic drug?

PMID- 22372783
TI  - Cytomegalovirus and Epstein-Barr virus may be associated with some cases of
      cerebral palsy.
AB  - OBJECTIVE: Intrauterine infection is a risk factor for cerebral palsy. Previous
      work reported a high frequency of viral DNA in newborn screening cards from
      cerebral palsy cases and controls possibly due to contamination. METHODS:
      Retrospective case-control study using improved methodologies to minimize
      contamination during PCR-based detection of viral DNA sequences. Newborn
      screening cards of 339 Caucasian children with cerebral palsy and 594 controls
      were examined. Viruses tested were herpes simplex viruses 1 and 2 (HSV1 and 2),
      varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV),
      human herpes viruses 6, 7 and 8 (HHV6, HHV7 and HHV8), and parvovirus B19.
      Genotyping was performed on DNA extracted from dried blood spots. RESULTS: CMV
      and EBV were detected in 5 (1.5%) and 3 (0.9%) of 339 cases, respectively, but
      not in controls (p = 0.047 and 0.006). Frequencies of detection of the other
      viruses examined were similar for cases and controls. DNA from at least one of
      the nine viruses tested was found in 4.4% of cases and 3.1% of controls [OR 1.4
      95% CI (0.71-2.76)]. CONCLUSION: Evidence of congenital viral infection was
      uncommon in cases of cerebral palsy and controls. However, CMV and EBV were
      significantly associated with cerebral palsy.

PMID- 22372785
TI  - The usefulness of the serum s100b protein for predicting delayed neurological
      sequelae in acute carbon monoxide poisoning.
AB  - CONTEXT: Some patients with acute carbon monoxide poisoning will experience
      delayed neurological sequelae. Several factors associated with delayed
      neurological sequelae have been reported, but these factors are unsatisfactory
      for the assessment of unconscious patients. OBJECTIVE: The aim of this study was
      to assess the usefulness of the serum S100B protein as a biochemical marker for
      predicting delayed neurological sequelae. MATERIALS AND METHODS: In this
      retrospective study, we evaluated the data for patients who visited an emergency
      medical center once during a period of 7 months. The enrollment criteria were the
      diagnosis of acute carbon monoxide poisoning and the measurement of the serum
      S100B level. A standardized extraction using medical records was performed.
      RESULT: A total of 71 patients were enrolled, and 10 patients (14.1%) presented
      delayed neurological sequelae. The delayed neurological sequelae group had a
      longer duration of carbon monoxide exposure, a longer duration of loss of
      consciousness, and a worse mental status (p-value < 0.001). In addition, the
      S100B protein levels were higher in the delayed neurological sequelae group
      (0.891 vs. 0.063, p-value < 0.001). Multiple logistic regression analysis showed
      that only the serum S100B protein level was independently associated with the
      development of delayed neurological sequelae (OR, 120.594; 95% CI, 4.194
      3467.220), and a serum S100B protein level of more than 0.165 MUg/L predicted the
      development of delayed neurological sequelae (sensitivity 90%, specificity 87%).
      DISCUSSION AND CONCLUSION: In the present study, the level of serum S100B protein
      was found to be useful for evaluating acute CO poisoning patients and was found
      to be an independent predictor of the development of DNS after acute CO
      poisoning.

PMID- 22372784
TI  - Multicenter assessment of the revisit risk for a further drug-related problem in
      the emergency department in cocaine users (MARRIED-cocaine study).
AB  - INTRODUCTION AND OBJECTIVES: Emergency departments (EDs) in Spanish hospitals
      daily attend a large number of patients for adverse reactions or clinical
      complications resulting from cocaine use. After discharge, some of these patients
      revisit the ED for the same reason within a year. The objective of the present
      study was to quantify the rate of such revisits and identify the factors
      associated with them. METHOD: We performed a retrospective, multicenter study
      with cohort follow-up and without a control group, conducted in the EDs of six
      Spanish hospitals during 12 months (January-December 2009). We included all ED
      patients attended for cocaine-related symptoms who reported recent cocaine use
      and those with cocaine-positive urine analysis by immunoassay without declared
      consumption. Twelve independent variables assessed for each hospital ED were
      collected: sex, age, place of consumption, month, day, and time of consumption,
      mode of arrival at the ED, discharge diagnosis, psychiatric assessment on the ED
      episode, concomitant drugs, destination on discharge, and history of previous ED
      visits related with drug use and alcohol use. The dependent variable was a
      subsequent visit to the ED associated with drug use, identified using the
      computerized hospital admissions system. RESULTS: The study included 807
      patients, of whom 6.7% revisited the ED within 30 days, 11.9% within 3 months and
      18.9% within 1 year. The variables significantly associated with ED revisits
      were: presence of clinical manifestations directly related to cocaine (p < 0.05),
      ED attendance on a working day (p < 0.05), history of ED visits related with the
      consumption of alcohol (p < 0.001) or drugs (p < 0.001), and the need for urgent
      consultation with a psychiatrist (p < 0.001), although only the last four were
      independent predictors in multivariate analysis. We derived a score based on
      these variables to predict risk of revisits (MARRIED-score, ranging from 0 to 400
      points), which had a reasonably good predictive value for revisit (area under ROC
      of 0.75; 95% CI 0.71-0.79).

PMID- 22372786
TI  - European viper envenomings: Assessment of ViperfavTM and other symptomatic
      treatments.
AB  - The treatment of European viper envenomings is based on IV antivenom infusions.
      ViperfavTM contains purified F(ab')(2) fragments of equine antibodies, and a 4 ml
      vial can neutralize 500-1000 mouse LD50 of Vipera aspis, V. ammodytes and V.
      berus venoms and is known to be safe and efficient. Assessments of ViperfavTM
      (dosage and timing of infusions) and of symptomatic treatments such as low
      molecular-weight heparin (LWHM), corticosteroids and the routine use of
      antibiotic therapy have not as yet been reported. OBJECTIVES: The objective was
      to compare the efficacy and safety of ViperfavTM as a function of the time to
      infusion and to assess other symptomatic treatments given for European viper
      bites such as antibiotics, corticosteroids and LWMH. METHODS: A prospective case
      review study of viper envenomings treated with ViperfavTM was compiled by the
      Angers Poisons Centre. The endpoints chosen were as follows: duration of hospital
      stay, complications (haematoma, infection) and persistent functional discomfort
      on day 15. Statistical studies were based on multivariate data analysis (MVA).
      RESULTS: 268 moderate or severe envenomings (Grades II and III) recorded in
      adults and children between 1999 and 2009 were included in the study. A time to
      the ViperfavTM infusion < 10 h after the bite (179 patients vs. 72) significantly
      reduced the incidence of haematomas (OR 2.3; p < 0.006), functional discomfort
      (OR 3.7; p < 10 - 4) and length of hospital stay (OR 2.1; p < 0.03). Multiple
      doses of ViperfavTM (2 or 3 vials in 22 patients vs. 246 treated with 1 vial) did
      not improve the selected endpoints. Routine antibiotic therapy was prescribed in
      102 patients (vs. 166 patients without) and no significant difference was seen
      with respect to the endpoints. Moreover, no local or systemic infections were
      recorded in the non-antibiotic group. Corticosteroids were prescribed in 36
      patients (vs. 232 without) but they did not significantly improve the endpoints
      or oedema. LMWH in 32 patients (vs. 236 without) increased the length of hospital
      stay (OR 3.2; p < 0.009 and the level of significantly persistent functional
      discomfort at day 15 (OR 3.7; p < 0.003). CONCLUSIONS: A single infusion of
      ViperfavTM (one vial) was effective whatever the grade of envenomation, and
      multiple doses did not improve the outcome. ViperfavTM was most effective when
      given soon (< 10 h) after envenoming. The routine use of antibiotic therapy was
      not necessary. Corticosteroids did not improve the endpoints selected, and we do
      not recommend the use of LMWH as this increased persistent functional discomfort
      and the length of hospital stay.

PMID- 22372787
TI  - Blue vitriol poisoning: a 10-year experience in a tertiary care hospital.
AB  - BACKGROUND AND AIM: Copper sulphate poisoning, while unusual in the West, is not
      rare in the Indian subcontinent, and mostly suicidal in intent. Unfortunately,
      data available on copper sulphate poisoning is limited. This study was planned to
      identify common presentations and complications of copper sulphate poisoning, and
      biochemical parameters that predict outcomes in these patients. MATERIALS AND
      METHODS: A retrospective analysis of 35 patients presenting with copper sulphate
      poisoning over a period of 10 years (2001-2010) was performed, based on review of
      their medical records. Paediatric cases and patients with concomitant poisoning
      with other substances were excluded. Clinical presentation, laboratory
      parameters, complications and treatment modalities were studied. RESULTS: Of the
      35 cases, 23 were females (65.71%). Mean age was 29.18 +/- 10.77 years. Vomiting
      was the commonest symptom (85.71%) followed by diarrhoea (45.71%), epigastric
      pain (42.86%) and rectal passage of blood (31.43%). Fourteen (40%) patients had
      pre-existing psychiatric disease. Medical signs included pallor (37.14%) and
      icterus (37.14%). Major complications included hemolysis (68.57%), renal failure
      (51.43%), acute hepatitis (45.71%) and upper gastrointestinal bleed (40%). Mean
      serum copper at presentation was 104.53 +/- 56.67 MUg/dL; mean methemoglobin
      level was 9.59 +/- 8.28%. Twenty-seven patients survived yielding a mortality
      rate of 22.9%. Peak serum aspartate and alanine aminotransferases were
      significantly lower (223.8 +/- 247.3 U/L, 66.3 +/- 92.2 U/L) in survivors
      compared to non-survivors (489.6 +/- 374.0 U/L, 192.9 +/- 168.7 U/L; p = 0.03, p
      < 0.01, respectively). Analysis by receiver operating characteristic (ROC) curve
      showed sensitivities of 100% and 85.7%, and specificities of 73.1% and 69.2%,
      respectively for peak serum alanine aminotransferase levels greater than 55 U/L,
      and peak serum aspartate aminotransferase levels greater than 234 U/L in
      predicting mortality. CONCLUSION: Copper sulphate is a potent poison that can
      involve multiple organ systems. Elevated levels of serum aspartate and alanine
      aminotransferases beyond the aforementioned values can identify patients at
      greater risk of mortality, allowing for institution of aggressive treatment.

PMID- 22372788
TI  - Effects of a provincial ban of two toxic organophosphorus insecticides on
      pesticide poisoning hospital admissions.
AB  - BACKGROUND: Pesticide self-poisoning causes one third of global suicides. Sri
      Lanka halved its suicide rate by banning WHO Class I organophosphorus (OP)
      insecticides and then endosulfan. However, poisoning with Class II toxicity OPs,
      particularly dimethoate and fenthion, remains a problem. We aimed to determine
      the effect and feasibility of a ban of the two insecticides in one Sri Lankan
      district. METHODS: Sale was banned in June 2003 in most of Polonnaruwa District,
      but not Anuradhapura District. Admissions with pesticide poisoning to the
      district general hospitals was prospectively recorded from 2002. RESULTS:
      Hospital admissions for dimethoate and fenthion poisoning fell by 43% after the
      ban in Polonnaruwa, while increasing by 23% in Anuradhapura. The pesticide case
      fatality fell from 14.4% to 9.0% in Polonnaruwa (odds ratio [OR] 0.59, 95%
      confidence interval [CI] 0.41-0.84) and 11.3% to 10.6% in Anuradhapura (OR 0.93,
      95%CI 0.70-1.25; p = 0.051). This reduction was not sustained, with case fatality
      in Polonnaruwa rising to 12.1% in 2006-2007. Further data analysis indicated that
      the fall in case fatality had actually been due to a coincidental reduction in
      case fatality for pesticide poisoning overall, in particular for paraquat
      poisoning. CONCLUSIONS: We found that the insecticides could be effectively
      banned from agricultural practice, as shown by the fall in hospital admissions,
      with few negative consequences. However, the ban had only a minor effect on
      pesticide poisoning deaths because it was too narrow. A study assessing the
      agricultural and health effects of a more comprehensive ban of highly toxic
      pesticides is necessary to determine the balance between increased costs of
      agriculture and reduced health care costs and fewer deaths.

PMID- 22372789
TI  - Poisonings in the Nordic countries in 2007: a 5-year epidemiological follow-up.
AB  - AIM: To map mortality and morbidity of poisonings in Denmark, Finland, Iceland,
      Norway and Sweden in 2007 and undertake a comparison with a corresponding study
      in 2002. METHODS: Morbidity was as for 2002 defined as acute poisoning (ICD-10
      codes, main and subsidiary diagnoses) treated in hospitals. The figures were
      extracted from the National Patient/Hospital Registers. Deaths recorded as acute
      poisoning (using corresponding ICD-10 codes) were collected from the National
      Cause of Death Registers. RESULTS: Annual mortality of acute poisonings per
      100,000 inhabitants (rate) for 2007 was 22.4 in Finland, an important increase
      from 16.7 per 100,000 in 2002. The increase was mainly due to a change in coding
      of alcohol, but also represented a slight increase in fatal alcohol intoxications
      per se. The poisoning death rate in the other Nordic countries varied between 8
      13 and was at the same level as for 2002. The morbidity rates for 2007 between
      158-285 per 100,000 inhabitants represented a slight increase compared to 2002
      figures. CONCLUSION: The increase in poisoning death rate for alcohol, and thus
      total rate in Finland in 2007 compared to 2002, has further increased the gap to
      the other Nordic countries. Poisoning morbidity rates in the Nordic countries are
      of the same level, but the variability shown indicates that more harmonization
      and collaboration is needed to increase the data quality.

PMID- 22372790
TI  - Hypoglycaemia: a little known effect of Venlafaxine overdose.
AB  - We report the case of a 39-year-old woman who presented with serotonin syndrome
      and hypoglycaemia likely due to intoxication with a very high dose of
      venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first
      by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood
      glucose normalized after injection of octreotide, eliminating the need for
      hypertonic glucose. Octreotide has been shown to decrease glucose requirements
      and the number of hypoglycaemic episodes in patients with sulfonylurea-induced
      hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic
      episodes due to massive venlafaxine overdose has not yet been described.

PMID- 22372791
TI  - Acute lung injury following refrigeration coil deicing.
AB  - We report a case of a worker who developed ALI requiring mechanical ventilatory
      support after attempting to melt ice condensate by applying the flame of an oxy
      acetylene torch to refrigeration coils charged with a halocarbon refrigerant in a
      closed environment. A discussion of possible etiologies are discussed, including
      phosgene, carbonyl fluoride, and nitrogen oxides. Primary prevention with
      adequate respiratory protection is recommended whenever deicing is performed in a
      closed space environment.

PMID- 22372792
TI  - Woman with a hand ulcer.
AB  - A 20-year-old woman presented to the emergency department for evaluation of a
      wound to left hand (Fig. 1). She admitted having a history of chronic severe
      headaches requiring daily use of analgesics. She first noted the ulcer
      approximately 10 months prior to presentation. Her examination was remarkable for
      a 10-cm by 8-cm ulceration to the dorsum of her left hand with exposed and
      necrotic metacarpals. Fibrous exudate was present in the wound-bed, and the ulcer
      was associated with a foul odor. She was afebrile on presentation with a
      peripheral white blood cell count of 6.4 x109/L, CRP 1.9 mg/dL, and ESR 15 mm/h.

PMID- 22372793
TI  - Intravenous lipid emulsion for intentional Chloroquine poisoning.

PMID- 22372794
TI  - Polymeric Display of Proteins through High Affinity Leucine Zipper Peptide
      Adaptors.
AB  - The polymeric display of proteins is a method that could be used to increase the
      immunogenicity of antigens and to enhance the interaction strength of binding
      domains for their target ligands through an avidity effect. However, the coupling
      of proteins to oligomeric scaffolds is challenging. The chemical conjugation and
      recombinant fusion techniques have limitations that prevent their general use. In
      this work we describe a simple and effective method for coupling proteins to the
      decameric structure of  Brucella abortus  Lumazine Synthase based on the use of a
      pair of high affinity heterodimeric coiled coil peptides complementary fused to
      the scaffold and the target protein. Results obtained with a series of proteins
      demonstrate the capability of this approach to generate polyvalent particles.
      Furthermore, we show that the method is able to increase the immunogenicity of
      antigens and produce polyfunctional particles with promising biomedical and
      nanotechnological applications.

PMID- 22372795
TI  - The effect of once daily omeprazole and succinic acid (VECAM) vs once daily
      omeprazole on 24-h intragastric pH.
AB  - BACKGROUND: Parietal cell H(+)/K(+) ATPase activation is essential for optimal
      proton pump inhibitor (PPI) activity. Succinic acid (SA) was shown to induce
      gastric acid secretion. VECAM is a combination of omeprazole (OMP) and SA. To
      compare the effect of once daily bedtime dosing of VECAM 40 and VECAM 20 without
      food vs OMP 20 mg administered before breakfast on gastric acidity. METHODS: Open
      label, randomized, crossover study enrolling 36 healthy subjects comparing the
      study treatments at steady state for 24 h intragastric pH monitoring. KEY
      RESULTS: The median percent time intragastric pH > 4 demonstrated that VECAM 40
      was superior to VECAM 20 (65.7%vs 49.1%P < 0.0001) and OMP 20 mg (65.7%vs 47.6%P
      = 0.005) during 24 h. VECAM 40 was superior to VECAM 20 (52.8%vs 38.8%P = 0.0079)
      and OMP 20 mg (52.8%vs 27.2%P < 0.0001), and VECAM 20 was superior to OMP 20 mg
      (38.8 vs 27.2 P = 0.0069) during the nighttime. VECAM 20 and OMP 20 mg were
      comparable during 24 h. CONCLUSIONS & INFERENCES: VECAM 40 and VECAM 20 were
      significantly better in maintaining intragastric pH > 4 during the nighttime than
      OMP 20 mg. Succinic acid eliminates the need for a subsequent meal for
      intragastric pH control by VECAM.

PMID- 22372796
TI  - ERCP and pregnancy.

PMID- 22372797
TI  - ERCP during pregnancy.
AB  - BACKGROUND AND AIMS: ERCP during pregnancy is always challenging for the entire
      team performing the endoscopic intervention. In this study techniques and
      different interventional aspects used at several centres about the clinical
      experience on ERCP in pregnant women are analyzed. PATIENTS AND METHODS: the
      practice on ERCP in pregnant women in six centres during a period of ten years is
      reported. RESULTS: eleven patients were included in the study. Mean age was 30.6
      years. Indication for ERCP was always symptomatic common bile duct stone (CBDS)
      disease. Before the procedure abdominal ultrasound was performed at all times and
      magnetic resonance cholangiopancreatography in four occasions. Conscious sedation
      by means of midazolam and fentanyl or meperidine was applied. Sphincterotomes and
      guidewires were used for bilary cannulation. Sometimes, rapid exchange platforms
      with short-length guidewires controlled by the same endoscopist were employed.
      Biliary cannulation was confirmed in 9 occasions by bile aspiration. In five
      procedures, a mean of 30 seconds of fluoroscopy was used, both to verify
      cannulation and to corroborate complete CBDS clearance. These patients had the
      pelvic zone protected with a lead shield and radiation dose was measured. Ten
      biliary sphincterotomies were performed followed by CBDS extraction. Two plastic
      stents were inserted. Relief of biliary obstruction was attained in all
      circumstances. Only one patient had hyperamylasemia after ERCP. All pregnant
      women had healthy foetuses with normal deliveries. CONCLUSIONS: with experience,
      ERCP appears to be a safe technique during pregnancy. With simple measures
      fluoroscopic time can be diminished or even abolished. It seems that ERCP during
      pregnancy is underused in our working areas, although it has shown to be a useful
      technique for relieving biliary obstruction.

PMID- 22372798
TI  - Is safety infliximb during pregnancy in patients with inflammatory bowel disease?
AB  - BACKGROUND: in most cases, inflammatory bowel disease (IBD) debuts at
      reproductive age. The data available in the literature show infliximab (IFX) to
      be a safe drug during pregnancy but there is very little evidence about the
      activity of the disease following drug withdrawal during pregnancy. AIMS:
      determine the drug's safety in pregnant women in our setting and assess its
      effect on the foetus, drawing on the experience of several hospitals. Secondly,
      observe the effect of treatment withdrawal on disease activity during pregnancy.
      MATERIAL AND METHODS: a retrospective study was conducted of women with IBD who
      had received IFX treatment during pregnancy in five hospitals in Spain. Disease
      activity was assessed using Crohn's Disease Activity Index, while UC was assessed
      using the Truelove-Witts Index in each trimester of pregnancy. Gestational age,
      weight and diseases in the foetus were determined at birth. RESULTS: the study
      included 12 women with a mean age of 29 years; 4 had ulcerative colitis and 8
      Crohn's disease, with mean disease duration of 7 years. All but one, who was
      diagnosed during pregnancy, was receiving IFX treatment at conception. Six
      patients received uninterrupted treatment throughout the pregnancy, 2 requested
      voluntary interruption and in 3 cases treatment was interrupted in the third
      trimester as a precaution. They received a mean IFX dose of 400 mg every 8 weeks.
      Of the 6 patients who received continuous treatment, in 50% disease was held in
      remission. The 6 remaining patients suspended treatment for different reasons,
      presenting disease recurrence in all but one case (83.3%). Eight deliveries were
      vaginal and 4 by caesarean section. Newborns presented no congenital anomalies,
      intrauterine growth retardation or low birth weight and there was only one
      premature delivery. CONCLUSIONS: although cases included in the study are not
      significant, in our experience, IFX during pregnancy is a safe treatment for the
      mother and the foetus. In fact, in our study and in some cases, its withdrawal
      may lead to a worsening of the disease. However, further control studies are
      required with larger samples to obtain more representative findings.

PMID- 22372799
TI  - Efficacy of an enterovaccine in recurrent episodes of diarrhea in the dog: a
      pilot study.
AB  - Recurrent episodes of self-limiting diarrhea in the dog, due to sudden dietary
      changes and to stressful or exciting situations, are conditions sometimes
      difficult to treat. Colifagina((r)), a commercially available bacterial
      enterovaccine, showed, in previous studies performed on experimentally induced
      colitis in mice, to be able to improve both disease activity index and
      histological appearance, increase colonic secretion of IgA, and reduce
      inflammatory chemokine secretion. In the present study Colifagina((r)) was
      administered to five dogs presenting recurrent episodes of self-limiting diarrhea
      and to one dog presenting chronic diarrhea. During the follow-up period, almost
      all patients decreased the number of episodes of abnormal defecation and the
      fecal score of such episodes improved in five out of six dogs. Even if further
      studies are needed to understand the exact potential of the compound, in dogs
      presenting recurrent episodes of self-limiting diarrhea due to sudden dietary
      changes and/or stressing or exciting situations, Colifagina((r)) seems to be
      helpful in managing most of these patients.

PMID- 22372800
TI  - Thalidomide in refractory bleeding due to gastrointestinal angiodysplasias.
AB  - OBJECTIVES: to assess the efficacy of thalidomide in the treatment of relapsed or
      refractory bleeding secondary to gastrointestinal angiodysplasia. MATERIAL AND
      METHODS: we carried out a prospective study of 12 patients with bleeding due to
      gastrointestinal angiodysplasia refractory to conventional therapy who were
      treated with thalidomide. For each patient, we considered: age, sex, underlying
      disease, previous therapies, dose and duration of thalidomide treatment,
      evolution of haemoglobin levels and adverse effects of treatment. The data
      obtained were analysed using descriptive statistics with SPSS v. 16. RESULTS:
      seven men and 5 women with a mean age of 77 years were included in the present
      study. Five had some underlying pathology and all of them had received prior
      endoscopic/octreotide treatment. The dose of thalidomide administered was 200
      mg/24 h and the duration of the treatment four months, with the exception of two
      patients in whom treatment was discontinued because of adverse side effects. Mean
      haemoglobin concentration before onset of treatment was 6.5 g/dL, at two months
      it was 11.3 g/dL and at the end of treatment 12.1 g/dL. CONCLUSIONS: thalidomide
      is an effective treatment in gastrointestinal bleeding due to angiodysplasia, but
      it was withdrawn due to side effects in 16% of the patients included in our
      study.

PMID- 22372801
TI  - Current endoscopic techniques in the treatment of obesity.
AB  - BACKGROUND: in recent years new endoscopic strategies and techniques for the
      treatment of obesity have emerged and developed. AIM OF THE STUDY: in this
      article we will review and analyze the current state of the following techniques
      and the basic differential characteristics between each of them: balloons and
      prosthesis, injection of substances, systems of sutures, malabsorptives
      techniques and others currently in research. METHODS: we will evaluate the
      endoscopic technique and their main indications, results, tolerances,
      complications and adverse effects observed, reporting our personal experience and
      in relation with an extensive literature review. RESULTS: comparatively with the
      most widespread technique of the Bioenterics balloon, the Spatz balloon can
      provide greater weight loss but with worse tolerance and more complications and
      the Heliosphere Bag gets a similar weight loss but with greater technical
      difficulty. Other balloons and prosthesis (Ullorex, Semistationary, Silimed,
      Endogast) still require technical improvements and higher studies. The injection
      of botulinum toxin, although secure, seems to offer a smaller and more transient
      efficacy. Suture systems (TOGa, endoluminal vertical gastroplasty and POSE)
      appear to be effective but are technically more laborious. Malabsorptives
      procedures (Endobarrier, ValenTX) are somewhat laborious but effective,
      particularly indicated in obese patients with type 2 diabetes mellitus.
      CONCLUSIONS: the development of new endoscopic techniques and improvement in
      existing designs, suggest an increasingly important role of the endoscopist in
      the treatment of obesity. We consider it important to individually select and use
      the endoscopic technique, depending on the desirable outcomes (efficacy,
      tolerance, safety, adverse effects and risks) and the experience of each
      hospital. We believe that these techniques should be applied by specifically
      trained endoscopists in specialized hospitals.

PMID- 22372802
TI  - External and internal appearance of hepatorenal polycystic disease.

PMID- 22372803
TI  - Sigmoid colon perforation due to a foreign body ingestion.

PMID- 22372804
TI  - Pyoderma gangrenosum with extensive perianal involvement.

PMID- 22372805
TI  - Hepatoportal sclerosis clinical different evolutionary stages: presentation of 3
      cases and literature review.
AB  - Hepatoportal sclerosis (HPS) is characterized by presinusoidal intrahepatic
      portal hypertension associated with splenomegaly and anemia in patients with non
      cirrhotic liver. Liver biopsy is essential, especially to rule out other
      processes. Being a disease of unknown etiology, the majority of cases have been
      described in eastern countries. However, it may be an underdiagnosed disease in
      the West. Symptoms are related to portal hypertension and the clinical spectrum
      is wide, ranging from anemia with normal liver function tests to bleeding due to
      esophageal varices. Treatment is directed to the complications and the prognosis
      is better than in patients with cirrhosis.We report three cases of HPS presenting
      at different clinical stages and the findings of liver biopsies, the clinical
      outcomes and a review of scientific literature.

PMID- 22372806
TI  - [Intraductal papillary mucinous neoplasia of the pancreas].

PMID- 22372807
TI  - Gastrointestinal bleeding secondary to intestinal neurofibromatosis.

PMID- 22372808
TI  - Differential diagnosis between autoimmune pancreatitis and pancreatic cancer
      about a case.

PMID- 22372809
TI  - Gastroduodenal phytobezoar treated with Coca-Cola(r).

PMID- 22372810
TI  - Endovascular treatment of iatrogenic hemobilia.

PMID- 22372811
TI  - Predictable bad evolution of an acute pancreatitis.

PMID- 22372812
TI  - Giant fibrovascular esophageal tumor. Endoscopic vision.

PMID- 22372816
TI  - Fluorophosphonylated nucleoside derivatives as new series of thymidine
      phosphorylase multisubstrate inhibitors.
AB  - The synthesis of new class of potential TPase inhibitors containing a
      difluoromethylphosphonate function as phosphate mimic is reported. This new
      series was prepared from a readily available fluorinated building block in few
      steps. Two series were evaluated as potential inhibitors: a linear series and a
      conformational constrained series. The activity of these multisubstrate
      inhibitors depends on the size of the spacer introduced between the pyrimidine
      ring and the phosphonate function. Best results were observed from triazolyl
      derivatives, easily obtained from propargylthymine and corresponding azides.

PMID- 22372815
TI  - Compaction enhances extracellular matrix content and mechanical properties of
      tissue-engineered cartilaginous constructs.
AB  - Many cell-based tissue-engineered cartilaginous constructs are mechanically
      softer than native tissue and have low content and abnormal proportions of
      extracellular matrix (ECM) constituents. We hypothesized that the load-bearing
      mechanical properties of cartilaginous constructs improve with the inclusion of
      collagen (COL) and proteoglycan (PG) during assembly. The objectives of this work
      were to determine (1) the effect of addition of PG, COL, or COL+PG on compressive
      properties of 2% agarose constructs and (2) the ability of mechanical compaction
      to concentrate matrix content and improve the compressive properties of such
      constructs. The inclusion of COL+PG improved the compressive properties of
      hydrogel constructs compared with PG or COL alone. Mechanical compaction
      increased the PG and COL concentrations in and compressive stiffness of the
      constructs. Chondrocytes included in the constructs maintained high viability
      after compaction. These results support the concepts that the assembly of
      cartilaginous constructs with COL+PG and application of mechanical compaction
      enhance the ECM content and compressive properties of engineered cartilaginous
      constructs.

PMID- 22372817
TI  - Lymphoid organ cell culture system from Penaeus monodon (Fabricius) as a platform
      for white spot syndrome virus and shrimp immune-related gene expression.
AB  - Shrimp cell lines are yet to be reported and this restricts the prospects of
      investigating the associated viral pathogens, especially white spot syndrome
      virus (WSSV). In this context, development of primary cell cultures from lymphoid
      organs was standardized. Poly-l-lysine-coated culture vessels enhanced growth of
      lymphoid cells, while the application of vertebrate growth factors did not,
      except insulin-like growth factor-1 (IGF-1). Susceptibility of the lymphoid cells
      to WSSV was confirmed by immunofluoresence assay using monoclonal antibody
      against the 28 kDa envelope protein of WSSV. Expression of viral and immune
      related genes in WSSV-infected lymphoid cultures could be demonstrated by RT-PCR.
      This emphasizes the utility of lymphoid primary cell culture as a platform for
      research in virus-cell interaction, virus morphogenesis, up and downregulation of
      shrimp immune-related genes, and also for the discovery of novel drugs to combat
      WSSV in shrimp culture.

PMID- 22372818
TI  - Near infrared fluorescence imaging with ICG in TECAB surgery using the da Vinci
      Si surgical system in a canine model.
AB  - BACKGROUND: This study assessed the clinical utility of near-infrared
      fluorescence imaging using indocyanine green in off-pump beating heart total
      endoscopic and robotic-assisted coronary artery bypass using the fluorescence
      imaging system for the da Vinci Si on a canine model for vessel identification,
      graft patency, and correlation of graft patency with ultrasound transit-time flow
      measurement probe. METHODS: Beating heart total endoscopic robotic-assisted
      coronary artery bypass was performed on eight canine using indocyanine green and
      fluorescence imaging to identify the internal mammary artery prior to harvesting,
      the coronary vessel anatomy, and the patency of the beating heart total
      endoscopic coronary artery bypass anastomosis. Three to four injections of
      indocyanine green with a dose of 1.25 mg to 2.5 mg were administered per animal.
      Transit-time flow was measured in each of the dogs. RESULTS: High definition 3D
      images were obtained. The camera working distance, indocyanine green dosage,
      internal mammary artery visualization, coronary artery visualization, patency by
      indocyanine green injection, and patency by transit-time flow were recorded. Six
      cases were completed successfully, and all demonstrated correlation between
      indocyanine green measurements of flow, and the transit-time flow measurement.
      CONCLUSION: Use of near-infrared fluorescence with indocyanine green was feasible
      in our study, and would be of great benefit during total endoscopic robotic
      assisted coronary artery bypass using the fluorescence imaging-capable da Vinci
      Si system to help identify the internal mammary artery, delineate the coronary
      anatomy, and also determine patency of the anastomoses. This procedure correlated
      well with transit-time flow measurement.

PMID- 22372819
TI  - Postnatal histomorphogenesis of the mandible in the house mouse.
AB  - The mandible of the house mouse, Mus musculus, is a model structure for the study
      of the development and evolution of complex morphological systems. This research
      describes the histomorphogenesis of the house mouse mandible and analyses its
      biological significance from the first to the eighth postnatal weeks.
      Histological data allowed us to test a hypothesis concerning modularity in this
      structure. We measured the bone growth rates by fluorescent labelling and
      identified the bone tissue types through microscopic analysis of histological
      cross-sections of the mandible during its postnatal development. The results
      provide evidence for a modular structure of the mouse mandible, as the alveolar
      region and the ascending ramus show histological differences throughout ontogeny.
      The alveolar region increases in length during the first two postnatal weeks by
      bone growth in the posterior region, while horizontally positioned incisors
      preclude bone growth in the anterior region. In the fourth postnatal week, growth
      dynamics shows a critical change. The alveolar region drifts laterally and the
      ramus becomes more vertical due to the medial growth direction of the coronoid
      region and the lateral growth of the ventral region of the ramus. Diet changes
      after weaning are probably involved in these morphological changes. In this way,
      the development of the masticatory muscles that insert on the ascending ramus may
      be particularly related to this shape modeling of the house mouse mandible.

PMID- 22372820
TI  - Spatio-temporal characteristics of the transfer free energy of apomyoglobin into
      the molecular crowding condition with trimethylamine N-oxide: a study with three
      types of the Kirkwood-Buff integral.
AB  - The transfer free energy (TFE) of apomyoglobin (AMb) from pure water into aqueous
      solution with trimethylamine N-oxide (TMAO) was investigated by all-atom
      molecular dynamics (MD) simulation combined with the Kirkwood-Buff (KB) integral
      method. The simulated TFE and the preferential interaction parameter correlated
      favorably with experimental values. In addition, the time-resolved KB integral
      revealed that a significant fluctuation in the TFE arose from the alteration in
      TMAO solvation around AMb. Furthermore, spatial decomposition of the KB integrals
      revealed how the local elements of the TFE are spatially distributed around AMb.
      These results revealed the spatio-temporal characteristics of the protein TFE
      into the molecular crowding condition with TMAO.

PMID- 22372821
TI  - Irisin: a new potential hormonal target for the treatment of obesity and type 2
      diabetes.

PMID- 22372822
TI  - Organ-specific responses of tomato growth and phenolic metabolism to nitrate
      limitation.
AB  - Phenolic compounds are secondary metabolites involved in plant innate chemical
      defence against pests and diseases. Their concentration varies depending on plant
      tissue and also on genetic and environmental factors, e.g. availability of
      nutrient resources. This study examines specific effects of low (LN) and high
      (HN) nitrogen supply on organ (root, stem and leaf) growth and accumulation of
      major phenolics [chlorogenic acid (CGA); rutin; kaempferol rutinoside (KR)] in
      nine hydroponically grown tomato cultivars. LN limited shoot growth but did not
      affect root growth, and increased concentrations of each individual phenolic in
      all organs. The strength of the response was organ-dependent, roots being more
      responsive than leaves and stems. Significant differences were observed between
      genotypes. Nitrogen limitation did not change the phenolic content in shoots,
      whereas it stimulated accumulation in roots. The results show that this trade-off
      between growth and defence in a LN environment can be discussed within the
      framework of the growth-differentiation balance hypothesis (i.e. GDBH), but
      highlight the need to integrate all plant organs in future modelling approaches
      regarding the impact of nitrogen limitation on primary and secondary metabolism. 

PMID- 22372823
TI  - Combined effect of osteopontin and BMP-2 derived peptides grafted to an adhesive
      hydrogel on osteogenic and vasculogenic differentiation of marrow stromal cells.
AB  - The objective of this work was to investigate the combined effect of grafting the
      peptide corresponding to amino acid residues 162-168 of osteopontin (OPD peptide)
      and the peptide corresponding to amino acid residues 73-92 of bone morphogenetic
      protein-2 (BMP peptide) to an RGD-conjugated inert hydrogel on osteogenic and
      vasculogenic differentiation of bone marrow stromal (BMS) cells. RGD-conjugated
      three-dimensional (3D) porous hydrogel scaffolds with well-defined cylindrical
      pore geometry were produced from sacrificial wax molds fabricated by fused
      deposition modeling rapid prototyping system. Propargyl acrylate and 4-pentenal
      were conjugated to the hydrogel for orthogonal grafting of BMP and OPD peptides
      by click reaction and oxime ligation, respectively. The OPD peptide was grafted
      by the reaction between aminooxy moiety of aminooxy-mPEG-OPD (mPEG = mini
      poly(ethylene glycol)) and the aldehyde moiety in the hydrogel. The BMP peptide
      was grafted by the reaction between the azide moiety of Az-mPEG-BMP and the
      propargyl moiety in the hydrogel. The hydrogels seeded with BMS cells were
      characterized by biochemical, immunocytochemical, and mRNA analyses. Groups
      included RGD control hydrogel (RGD), RGD and BMP peptides without OPD (RGD+BMP),
      RGD and BMP peptides with mutant OPD (RGD+BMP+mOPD), and RGD and BMP peptides
      with OPD (RGD+BMP+OPD) grafted hydrogels. The extent of mineralization of RGD,
      RGD+BMP, RGD+BMP+mOPD, and RGD+BMP+OPD groups after 28 days was 650 +/- 70, 990
      +/- 30, 850 +/- 30, and 1150 +/- 40 mg/(mg of DNA), respectively, indicating that
      the BMP and OPD peptides enhanced osteogenic differentiation of the BMS cells.
      The BMS cells seeded on RGD+BMP+OPD grafted hydrogels stained positive for
      vasculogenic markers alpha-SMA, PECAM-1, and VE-cadherin while the groups without
      OPD peptide (RGD+BMP and RGD+BMP+mOPD) stained only for alpha-SMA but not PECAM-1
      or VE-cadherin. These results were consistent with the significantly higher PECAM
      1 mRNA expression for RGD+BMP+OPD group after 21 and 28 days, compared to the
      groups without OPD. These findings suggest that the RGD+BMP+OPD peptides provide
      a favorable microenvironment for concurrent osteogenic and vasculogenic
      differentiation of progenitor marrow-derived cells.

PMID- 22372824
TI  - Microbiosensor for Alzheimer's disease diagnostics: detection of amyloid beta
      biomarkers.
AB  - Alzheimer's disease (AD) affects about 35.6 million people worldwide, and if
      current trends continue with no medical advancement, one in 85 people will be
      affected by 2050. Thus, there is an urgent need to develop a cost-effective, easy
      to use, sensor platform to diagnose and study AD. The measurement of peptide
      amyloid beta (Abeta) found in CSF has been assessed as an avenue to diagnose and
      study the disease. The quantification of the ratio of Abeta1-40/42 (or Abeta
      ratio) has been established as a reliable test to diagnose AD through human
      clinical trials. Therefore, we have developed a multiplexed, implantable
      immunosensor to detect amyloid beta (Abeta) isoforms using triple barrel carbon
      fiber microelectrodes as the sensor platform. Antibodies act as the
      biorecognition element of the sensor and selectively capture and bind Abeta1-40
      and Abeta1-42 to the electrode surface. Electrochemistry was used to measure the
      intrinsic oxidation signal of Abeta at 0.65 V (vs. Ag/AgCl), originating from a
      single tyrosine residue found at position 10 in its amino acid sequence. Using
      the proposed immunosensor Abeta1-40 and Abeta1-42 could be specifically detected
      in CSF from mice within a detection range of 20-50 nM and 20-140 nM respectively.
      The immunosensor enables real-time, highly sensitive detection of Abeta and opens
      up the possibilities for diagnostic ex vivo applications and research-based in
      vivo studies.

PMID- 22372825
TI  - Revealing the functionality of hypothetical protein KPN00728 from Klebsiella
      pneumoniae MGH78578: molecular dynamics simulation approaches.
AB  - BACKGROUND: Previously, the hypothetical protein, KPN00728 from Klebsiella
      pneumoniae MGH78578 was the Succinate dehydrogenase (SDH) chain C subunit via
      structural prediction and molecular docking simulation studies. However, due to
      limitation in docking simulation, an in-depth understanding of how SDH
      interaction occurs across the transmembrane of mitochondria could not be
      provided. RESULTS: In this present study, molecular dynamics (MD) simulation of
      KPN00728 and SDH chain D in a membrane was performed in order to gain a deeper
      insight into its molecular role as SDH. Structural stability was successfully
      obtained in the calculation for area per lipid, tail order parameter, thickness
      of lipid and secondary structural properties. Interestingly, water molecules were
      found to be highly possible in mediating the interaction between Ubiquinone (UQ)
      and SDH chain C via interaction with Ser27 and Arg31 residues as compared with
      earlier docking study. Polar residues such as Asp95 and Glu101 (KPN00728), Asp15
      and Glu78 (SDH chain D) might have contributed in the creation of a polar
      environment which is essential for electron transport chain in Krebs cycle.
      CONCLUSIONS: As a conclusion, a part from the structural stability comparability,
      the dynamic of the interacting residues and hydrogen bonding analysis had further
      proved that the interaction of KPN00728 as SDH is preserved and well agreed with
      our postulation earlier.

PMID- 22372827
TI  - [18F]fluoro-deoxy-glucose folate: a novel PET radiotracer with improved in vivo
      properties for folate receptor targeting.
AB  - The folate receptor (FR) is upregulated in various cancer types (FR-alpha
      isoform) and in activated macrophages (FR-beta isoform) which are involved in
      inflammatory and autoimmune diseases, but its expression in healthy tissues and
      organs is highly restricted to only a few sites (e.g kidneys). Therefore, the FR
      is a promising target for imaging and therapy of cancer and inflammation using
      folate-based radiopharmaceuticals. Herein, we report the synthesis and evaluation
      of a novel folic acid conjugate with improved properties suitable for positron
      emission tomography (PET). [(18)F]-fluoro-deoxy-glucose folate ([(18)F]3) was
      synthesized based on the click chemistry approach using 2-deoxy-2
      [(18)F]fluoroglucopyranosyl azide and a folate alkyne derivative. The novel
      radiotracer [(18)F]3 was produced in good radiochemical yields (25% d.c.) and
      high specific radioactivity (90 GBq/MUmol). Compared to previously published
      (18)F-folic acid derivatives, an increase in hydrophilicity was achieved by using
      a glucose entity as a prosthetic group. Biodistribution and PET imaging studies
      in KB tumor-bearing mice showed a high and specific uptake of the radiotracer in
      FR-positive tumors (10.03 +/- 1.12%ID/g, 60 min p.i.) and kidneys (42.94 +/-
      2.04%ID/g, 60 min p.i.). FR-unspecific accumulation of radioactivity was only
      found in the liver (9.49 +/- 1.13%ID/g, 60 min p.i.) and gallbladder (17.59 +/-
      7.22%ID/g, 60 min p.i.). No radiometabolites were detected in blood, urine, and
      liver tissue up to 30 min after injection of [(18)F]3. [(18)F]-fluoro-deoxy
      glucose-folate ([(18)F]3) is thus a promising PET radioligand for imaging FR
      positive tumors.

PMID- 22372828
TI  - Understanding hoarding in older adults.
AB  - Compulsive hoarding is a debilitating disorder that is only recently becoming
      understood. Hoarding has been studied primarily in the general population, with
      only a few researchers focusing on hoarding in older adults, even though the
      prevalence and severity of the disorder appears to increase with aging. Hoarding
      seriously affects the quality of one's life and can also cause safety and health
      problems for individuals and the community. Established treatments for hoarding
      are relatively new and often need to be extended over a long period of time.
      Nurses can play an important role in helping identify the problem of hoarding in
      older adults, determining the types of safety and health hazards that need to be
      addressed, and contacting the appropriate community agencies.

PMID- 22372829
TI  - Influence of endothelial cell protein C receptor on plasma clearance of factor
      VIIa.

PMID- 22372830
TI  - Meta-analysis of the effectiveness of chronic care management for diabetes:
      investigating heterogeneity in outcomes.
AB  - PURPOSE: The study aims to support decision making on how best to redesign
      diabetes care by investigating three potential sources of heterogeneity in
      effectiveness across trials of diabetes care management. METHODS: Medline, CINAHL
      and PsycInfo were searched for systematic reviews and empirical studies focusing
      on: (1) diabetes mellitus; (2) adult patients; and (3) interventions consisting
      of at least two components of the chronic care model (CCM). Systematic reviews
      were analysed descriptively; empirical studies were meta-analysed. Pooled effect
      measures were estimated using a meta-regression model that incorporated study
      quality, length of follow-up and number of intervention components as potential
      predictors of heterogeneity in effects. RESULTS: Overall, reviews (n = 15) of
      diabetes care programmes report modest improvements in glycaemic control.
      Empirical studies (n = 61) show wide-ranging results on HbA1c, systolic blood
      pressure and guideline adherence. Differences between studies in methodological
      quality cannot explain this heterogeneity in effects. Variety in length of follow
      up can explain (part of) the variability, yet not across all outcomes. Diversity
      in the number of included intervention components can explain 8-12% of the
      heterogeneity in effects on HbA1c and systolic blood pressure. CONCLUSIONS: The
      outcomes of chronic care management for diabetes are generally positive, yet
      differ considerably across trials. The most promising results are attained in
      studies with limited follow-up (<1 year) and by programmes including more than
      two CCM components. These factors can, however, explain only part of the
      heterogeneity in effectiveness between studies. Other potential sources of
      heterogeneity should be investigated to ensure implementation of evidence-based
      improvements in diabetes care.

PMID- 22372831
TI  - Rapid ambulatory pathway laser prostatectomy is safe: results within the global
      period.
AB  - What's known on the subject? and What does the study add? Laser prostatectomy is
      a commonly performed procedure for BOO, and has been shown to have short- and
      medium-term results equivalent to the gold standard procedure (i.e. TURP) in
      various studies. It also has an advantage over TURP in that it can be performed
      on patients who are taking anticoagulant medication. However, patients in most
      studies are admitted to the hospital overnight on continuous bladder irrigation
      and are discharged home the next day. The present study shows that it is safe and
      feasible to perform laser prostatectomy in an ambulatory fashion with discharge
      of patients within hours of their surgery. The discharge pathway is associated
      with minimal morbidity or the need for admission after surgery, and the reported
      short-term results are in accordance with the available literature on laser
      prostatectomy. OBJECTIVE: To investigate the feasibility and safety of a rapid
      ambulatory discharge pathway after holmium laser ablation of the prostate (HoLAP)
      for the treatment of benign prostatic hyperplasia. PATIENTS AND METHODS: The
      study group comprised a cohort of 65 consecutive patients undergoing HoLAP
      scheduled as a day surgical case by a single surgeon between January 2007 and
      December 2009. Patients were discharged from day surgery with a catheter in
      place, and returned for a voiding trial on postoperative day 3. Preoperative,
      intra-operative and postoperative parameters were reviewed with follow-up data
      for the 90-day global postoperative period. Statistical analysis employed
      Student's t-test with P < 0.05 (two-tailed) being considered statistically
      significant. RESULTS: The mean (range) patient age was 64 (41-87) years; mean
      (range) American Society of Anesthesiologists score was 2.2 (1-4); mean (sd)
      operation duration was 44 (17) min; and mean (sd) time after surgery until
      discharge was 149 (51) min. Postoperative complications included catheter
      occlusion (1.5%) and admission for haematuria (1.5%). There were no re-admissions
      after discharge from the hospital. Within the 90-day global period, 13 patients
      described lower urinary tract symptoms (20%), five patients had postoperative
      urinary retention (7.7%) and one patient had a urinary tract infection (1.5%).
      After surgery, mean American Urological Association Symptom Score decreased from
      21.3 to 7.6 (P < 0.001); mean quality of life score decreased from 4.04 to 1.38
      (P < 0.001); and mean post-void residual decreased from 190.2 to 46.4 mL (P <
      0.001). CONCLUSION: In appropriately selected patients, HoLAP can be safely
      performed as an ambulatory case with a rapid discharge pathway and minimal
      morbidity during the 90-day global period.

PMID- 22372832
TI  - Compound fetal presentation, uterine rupture and dreadful outcome: just a
      historical tale?

PMID- 22372833
TI  - Comment on "Material nature versus structural nurture: the embodied carbon of
      fundamental structural elements".

PMID- 22372834
TI  - Staurosporine induces apoptosis and necroptosis in cultured rat astrocytes.
AB  - Apoptosis and necroptosis are highly regulated, interconnected forms of a cell
      death. The distinction between them is critical, because necroptosis may cause
      significant cell loss and local inflammation, whereas apoptosis is essential for
      tissue homeostasis. The same stimulus can induce both apoptosis and necroptosis.
      Both forms of a cell death were detected in various pathologies, including
      pathologies in the central nervous system. Astrocytes are a large, heterogeneous
      cell population in the central nervous system, with many supportive,
      developmental functions. Although their demise may seriously impair normal
      functions of the central nervous system, it is still poorly understood. In this
      study, apoptosis and necroptosis were induced in cultured rat astrocytes by
      staurosporine. When a low concentration (10(-7) M) of staurosporine was applied,
      a significantly increased proportion of early apoptotic cells was detected after
      regeneration in a staurosporine free medium. The proportion of necroptotic cells
      was already increased without regeneration after 3 hours of exposure to
      staurosporine. When a higher (10(-6) M) concentration of staurosporine was
      applied, further significantly increased necroptosis was detected after
      regeneration in a staurosporine free medium. Necroptosis was significantly
      reduced when RIP1 kinase was inhibited by necrostatin-1, whereas inhibition of
      caspases with z-vad-fmk, an irreversible pan-caspase inhibitor, did not prevent
      necroptosis. This report of necroptosis induced by staurosporine represents a
      simple approach for the in vitro induction and detection of apoptosis and
      necroptosis.

PMID- 22372836
TI  - The breed and season effects on scrotal circumference and semen characteristics
      of hair sheep rams under tropical conditions.
AB  - The aim of the present work was to evaluate the breed and season effects on
      scrotal circumference (SC) and semen characteristics of 28 mature hair sheep rams
      kept under tropical conditions. SCs, sperm concentration (SPC) and abnormal sperm
      were significantly affected by breed effect (p < 0.001). The season effect was
      significant in SPC (p < 0.0001) while ejaculate volume, mass motility and SPC
      were affected by breed * season interaction effect (p < 0.001). It can be
      concluded that the magnitude of the breed and season effects were not sufficient
      to affect the reproductive capacity of hair sheep rams throughout the year.

PMID- 22372837
TI  - Family needs and profiles for children with cerebral palsy: understanding
      supports in times of scarcity.

PMID- 22372835
TI  - Design and synthesis of cannabinoid receptor 1 antagonists for peripheral
      selectivity.
AB  - Antagonists of cannabinoid receptor 1 (CB1) have potential for the treatment of
      several diseases such as obesity, liver disease, and diabetes. Recently,
      development of several CB1 antagonists was halted because of adverse central
      nervous system (CNS) related side effects observed with rimonabant, the first
      clinically approved CB1 inverse agonist. However, recent studies indicate that
      regulation of peripherally expressed CB1 with CNS-sparing compounds is a viable
      strategy to treat several important disorders. Our efforts aimed at rationally
      designing peripherally restricted CB1 antagonists have resulted in compounds that
      have limited blood-brain barrier (BBB) permeability and CNS exposure in
      preclinical in vitro and in vivo models. Typically, compounds with high
      topological polar surface areas (TPSAs) do not cross the BBB passively. Compounds
      with TPSAs higher than that for rimonabant (rimonabant TPSA = 50) and excellent
      functional activity with limited CNS penetration were identified. These compounds
      will serve as templates for further optimization.

PMID- 22372838
TI  - The effect of different fabrication steps on the marginal adaptation of two types
      of glass-infiltrated ceramic crown copings fabricated by CAD/CAM technology.
AB  - PURPOSE: Marginal adaptation is an important factor affecting the longevity of
      all-ceramic restorations, although the effects of different fabrication steps on
      marginal adaptation at various stages of fabrication are not fully understood.
      The purpose of this study was to assess with an in vitro model whether In-Ceram
      alumina (IA) or In-Ceram zirconia (IZ) copings produced by the CAD/CAM method
      would be clinically acceptable, and to evaluate the effect of each fabrication
      step (post-milling, post-trimming, and post-glass infiltration) on the marginal
      discrepancy of the coping. MATERIALS AND METHODS: A melamine tooth was prepared,
      duplicated, poured with inlay wax, and then cast with metal to fabricate a master
      die. An InLab 3D system was used to scan the master die and to design and mill
      the copings. Thirty IA and IZ copings each were developed with thicknesses of 0.6
      mm and a 30-MUm thick computer luting space. Epoxy resin replicas of the master
      die were fabricated, and the vertical and horizontal marginal discrepancies were
      measured using a Micro-Vu optical microscope at three stages of the fabrication
      (post-milling, post-trimming, post-infiltration). One-way ANOVA was used to
      analyze the data between the three stages of fabrication for each marginal
      discrepancy, and a t-test was used to compare vertical and horizontal marginal
      discrepancies (after glass infiltration) between IZ and IA copings RESULTS: There
      were no significant differences (p > 0.05) in the vertical marginal discrepancies
      (MUm) between IA (36 +/- 14) and IZ (40 +/- 14) copings after glass infiltration.
      ANOVA (comparing three stages within horizontal marginal discrepancy for IZ
      copings) showed that post-milling (40 +/- 26) > post-trimming (23 +/- 11) = post
      infiltration (19 +/- 13). ANOVA (comparing three stages within vertical marginal
      discrepancy for IZ copings) showed that post-milling (53 +/- 12) = post-trimming
      (47 +/- 13) > post-infiltration (36 +/- 14). ANOVA (comparing three stages within
      horizontal marginal discrepancy for IA copings) showed that post-milling (52 +/-
      28) > post-trimming (30 +/- 16) > post-infiltration (30 +/- 16). ANOVA (comparing
      three stages within vertical marginal discrepancy for IA copings) showed that
      post-milling (54 +/- 13) = post-trimming (56 +/- 26) > post-infiltration (40 +/-
      14). CONCLUSION: There was no significant difference in the marginal adaptation
      of both material copings. After the trimming process, the glass infiltration
      firing cycle improved the vertical marginal discrepancy for both IZ and IA
      copings. Clinical implications. IA and IZ copings fabricated by CAD/CAM
      technology have an acceptable marginal fit as documented in the literature, and
      the glass infiltration process improves the marginal fit after machining.

PMID- 22372839
TI  - Electrochemistry of nucleic acids.

PMID- 22372840
TI  - Tracking of climatic niche boundaries under recent climate change.
AB  - 1. Global climate has changed significantly during the past 30 years and
      especially in northern temperate regions which have experienced poleward shifts
      in temperature regimes. While there is evidence that some species have responded
      by moving their distributions to higher latitudes, the efficiency of this
      response in tracking species' climatic niche boundaries over time has yet to be
      addressed. 2. Here, we provide a continental assessment of the temporal structure
      of species responses to recent spatial shifts in climatic conditions. We examined
      geographic associations with minimum winter temperature for 59 species of winter
      avifauna at 476 Christmas Bird Count circles in North America from 1975 to 2009
      under three sampling schemes that account for spatial and temporal sampling
      effects. 3. Minimum winter temperature associated with species occurrences showed
      an overall increase with a weakening trend after 1998. Species displayed highly
      variable responses that, on average and across sampling schemes, contained a
      strong lag effect that weakened in strength over time. In general, the
      conservation of minimum winter temperature was relevant when all species were
      considered together but only after an initial lag period (c. 35 years) was
      overcome. The delayed niche tracking observed at the combined species level was
      likely supported by the post1998 lull in the warming trend. 4. There are limited
      geographic and ecological explanations for the observed variability, suggesting
      that the efficiency of species' responses under climate change is likely to be
      highly idiosyncratic and difficult to predict. This outcome is likely to be even
      more pronounced and time lags more persistent for less vagile taxa, particularly
      during the periods of consistent or accelerating warming. Current modelling
      efforts and conservation strategies need to better appreciate the variation,
      strength and duration of lag effects and their association with climatic
      variability. Conservation strategies in particular will benefit through
      identifying and maintaining dispersal corridors that accommodate diverging
      dispersal strategies and timetables.

PMID- 22372841
TI  - DNA barcoding and genetic diversity of phyllostomid bats from the Yucatan
      Peninsula with comparisons to Central America.
AB  - The mitochondrial cytochrome c oxidase subunit I gene is the standard DNA
      barcoding region used for species identification and discovery. We examined the
      variation of COI (454 bp) to discriminate 20 species of bats in the family
      Phyllostomidae that are found in the Yucatan Peninsula of southeastern Mexico and
      northern Guatemala and compared them genetically to other samples from Central
      America. The majority of these species had low intraspecific variation (mean =
      0.75%), but some taxa had intraspecific variation ranging to 8.8%, suggesting the
      possibility of cryptic species (i.e. Desmodus rotundus and Artibeus jamaicensis).
      There was a recurring biogeographic pattern in eight species with a separation of
      northern and southern Middle American localities. The Yucatan Peninsula was a
      discrete area identified in four species, whereas Panama was recovered in five
      species of phyllostomid bats. Our study establishes a foundation for further
      molecular work incorporating broader taxonomic and geographic coverage to better
      understand the phylogeography and genetic diversity that have resulted from the
      ecological constraints in this region and the remarkable differentiation of bats
      in the Neotropics.

PMID- 22372844
TI  - The association between neurodevelopmental disability and economic outcomes
      during mid-childhood.
AB  - BACKGROUND: There is a paucity of evidence on the association between childhood
      disability and economic outcomes. This study estimates the economic costs and
      health utilities associated with neurodevelopmental impairment or serious
      neurodevelopmental disability during the 11th year of life. METHODS: Standardized
      tests of cognitive ability and clinical assessments of functional abilities were
      performed on participants of a whole population study of extremely preterm
      children and term-born controls (EPICure). Profiles of children's use of health,
      social and education services, and descriptions of their health status using the
      Health Utilities Index Mark 2 and Mark 3 health status classification systems,
      were extracted from detailed questionnaires completed by the main parent.
      Descriptive and multiple regression techniques were used to explore the
      association between neurodevelopmental impairment or serious neurodevelopmental
      disability and two sets of economic outcomes; economic costs and health
      utilities. RESULTS: Mean health and social service costs over the 12-month period
      were estimated at L577 [standard error (SE): L141] among children without
      neurodevelopmental impairment, L831 (L112) among children with a mild
      neurodevelopmental impairment, L1053 (L176) among children with a moderate
      neurodevelopmental impairment and L1662 (L316) among children with a severe
      neurodevelopmental impairment. Mean health and social service costs were
      estimated at L1223 (L157) and L695 (L92) among children with and without serious
      neurodevelopmental disability, respectively. After controlling for clinical and
      sociodemographic confounders, mild, moderate and severe neurodevelopment
      impairment increased health and social service costs by an average of L397 (95%
      CI: L86, L707; P= 0.012), L655 (95% CI: L167, L1144; P= 0.009) and L1065 (95% CI:
      -L113, L2243; P= 0.076), respectively. Cost differences were accentuated when
      broader public sector costs were considered. The mean (SE) Health Utilities Index
      Mark 3 multi-attribute utility score for the children with neurodevelopmental
      disability was 0.652 (0.039), compared with 0.923 (0.009) for children without
      neurodevelopmental disability, generating a mean difference in utility score of
      0.272 (95% CI: 0.220, 0.323) that was statistically significant (P < 0.001).
      CONCLUSIONS: Our data should act as a significant new resource for economic
      analysts modelling the overall economic impact of childhood neurodevelopment
      impairment or disability or the cost-effectiveness of interventions targeted at
      neurodevelopmentally impaired or disabled children.

PMID- 22372845
TI  - Pharmacokinetics and milk secretion of gabapentin and meloxicam co-administered
      orally in Holstein-Friesian cows.
AB  - Management of neuropathic pain in dairy cattle could be achieved by combination
      therapy of gabapentin, a GABA analog and meloxicam, an nonsteroidal anti
      inflammatory drug. This study was designed to determine specifically the
      depletion of these drugs into milk. Six animals received meloxicam at 1 mg/kg and
      gabapentin at 10 mg/kg, while another group (n=6) received meloxicam at 1 mg/kg
      and gabapentin at 20 mg/kg. Plasma and milk drug concentrations were determined
      over 7 days postadministration by HPLC/MS followed by noncompartmental
      pharmacokinetic analyses. The mean (+/-SD) plasma C(max) and T(max) for meloxicam
      (2.89+/-0.48 MUg/mL and 11.33+/-4.12 h) were not much different from gabapentin
      at 10 mg/kg (2.87+/-0.2 MUg/mL and 8+/-0 h). The mean (+/-SD) milk C(max) for
      meloxicam (0.41+/-80.16 MUg/mL) was comparable to gabapentin at 10 mg/kg (0.63+/
      0.13 MUg/mL and 12+/-6.69 h). The mean plasma and milk C(max) for gabapentin at
      20 mg/kg p.o. were almost double the values at 10 mg/kg. The mean (+/-SD) milk to
      plasma ratio for meloxicam (0.14+/-0.04) was lower than for gabapentin (0.23+/
      0.06). The results of this study suggest that milk from treated cows will have
      low drug residue concentration soon after plasma drug concentrations have fallen
      below effective levels.

PMID- 22372846
TI  - Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass.

PMID- 22372847
TI  - Successful treatment of post-transplant Epstein-Barr virus-related
      meningoencephalitis by intravenous rituximab monotherapy.

PMID- 22372848
TI  - Absolute lymphocyte count at day + 21 predicts survival in patients with early
      stage diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide,
      adriamycin, vincristine and prednisone.
AB  - As lymphocytes play an active role in tumor control and as targets for
      immunochemotherapy, the prognostic significance of the absolute lymphocyte count
      (ALC) and its changes after rituximab, cyclophosphamide, adriamycin, vincristine
      and prednisone (R-CHOP) were investigated in patients with early-stage diffuse
      large B-cell lymphoma (DLBCL). The ALC was measured just before and on day + 21
      after R-CHOP in 230 consecutive patients with stage I and II DLBCL. During the
      median follow-up of 31.8 (range, 1.8-70.0) months, 200 patients (89.7%) achieved
      a complete response (CR) and 20 achieved a partial response (PR) (9.0%),
      representing an overall response rate of 98.7% among 223 evaluable patients.
      Analyzed according to various ALCs, only an ALC >= 1.3 * 10(9)/L at day + 21
      predicted longer progression-free (PFS) and overall survival (OS) in a univariate
      analysis (p < 0.001 and p = 0.001, respectively) as well as a higher CR rate
      adjusted to the revised International Prognostic Index (R-IPI) (odds ratio =
      2.824; p = 0.031). Moreover, a multivariate analysis revealed that a high ALC at
      day + 21 predicted a better time to progression (TTP) (HR = 0.335; p = 0.006),
      PFS (HR = 0.332; p < 0.001) and OS (HR = 0.309; p = 0.002), independent of the R
      IPI. In conclusion, the ALC after R-CHOP can be regarded as a prognostic marker
      in patients with early-stage DLBCL.

PMID- 22372849
TI  - Polyamidoamine dendron-bearing lipids as a nonviral vector: influence of dendron
      generation.
AB  - Recently, we demonstrated that octadecyl chains are important as alkyl chain
      moieties of polyamidoamine (PAMAM) dendron-bearing lipids for their serum
      resistant transfection activity [Bioconjugate Chem.2007, 18, 1349-1354]. Toward
      production of highly potent vectors, we examined the influence of the generation
      of dendron moiety on transfection activity of PAMAM dendron-bearing lipids having
      two octadecyl chains. We synthesized dendron-bearing lipids with PAMAM G1, G2,
      and G3 dendrons, designated respectively as DL-G1-2C(18), DL-G2-2C(18), and DL-G3
      2C(18). The DL-G2-2C(18) and DL-G3-2C(18) interacted with plasmid DNA effectively
      and formed stable lipoplexes with small sizes and spherical shape. However, DL-G1
      2C(18) interacted with plasmid DNA less effectively and formed tubular-shaped
      lipoplexes with lower stability and larger size. Cells took up DL-G2-2C(18) and
      DL-G3-2C(18) lipoplexes efficiently, but cellular uptake of the DL-G1-2C(18)
      lipoplexes was less efficient. Nevertheless, DL-G1-2C(18) lipoplexes achieved 100
      10 000 times higher levels of transgene expression, which was evaluated using
      luciferase gene as a reporter gene. Confocal scanning laser microscopic analysis
      of intracellular behaviors of the lipoplexes revealed that DL-G1-2C(18)
      lipoplexes generated free plasmid DNA molecules in the cytosol more effectively
      than other lipoplexes did. Moderate binding ability of DL-G1-2C(18) might be
      responsible for generation of lipoplexes which deliver plasmid DNA into cells,
      liberate it in the cytoplasm, and induce efficient transgene expression.

PMID- 22372850
TI  - Effects of the source of social comparison information on former cancer patients'
      quality of life.
AB  - OBJECTIVE: Life, following curative treatment, can be a struggle for former
      cancer patients. In this phase of their illness, social comparison information
      may help to improve a patient's quality of life (QOL). The objective of this
      study was to determine whether the effects of this information depend on the
      following two variables: (1) the individual's physical health and (2) the
      individual's sensitivity to social comparison. DESIGN: In the current study, the
      effects on a patient's QOL were tested that occur when they are listening to a
      psychological oncological expert talking about cancer patients' experiences.
      Three different recorded interviews with experts were compared (on negative
      emotions, effective coping, or both), and individual differences were tested as
      moderators. In addition, the expert source conditions were compared with a
      condition in which the source was not an expert but a former patient. METHODS: In
      a randomized field experiment, 154 Dutch former cancer patients (M(age) = 55
      years; 68% women) were assigned to one of the four conditions (three expert
      source and one former patient source condition). QOL was assessed after 2 months.
      RESULTS: The effects of the expert source conditions on QOL depended on the
      participants' physical health (good vs. poor) and on the participants'
      sensitivity to social comparison (whether the recipient reacts with contrast or
      identification), as indicated by significant three-way interactions (p < .001).
      Depending on these two variables, one of the three expert source conditions was
      at least as effective as the former patient source condition. CONCLUSIONS: The
      results show that desired and undesired effects are found when individual
      differences relevant to the processing of intervention information are examined.

PMID- 22372852
TI  - Right atrial myxoma--an unusual cause of pulmonary embolism.

PMID- 22372851
TI  - Molecular approaches identify known species, reveal cryptic species and verify
      host specificity of Chinese Philotrypesis (Hymenoptera: Pteromalidae).
AB  - Philotrypesis, a major component of the fig wasp community (Hymenoptera:
      Pteromalidae), is a model taxon for studying male fighting and mating behaviour.
      Its extreme sexual dimorphism and male polymorphism render species identification
      uncertain and in-depth research on its ecology, behaviour and other evolutionary
      topics challenging. The fig wasps' enclosed habitat within the syconia makes
      their mating behaviour inaccessible, to the extent of matching conspecific
      females and males. In this study, we combine morphological and molecular analyses
      to identify species of Philotrypesis sampled from south China and to associate
      their extraordinarily dimorphic genders and labile male morphologies.
      Morphological evaluations of females identify 22 species and 28 male morphs. The
      mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 2
      data detect 21 species using females, and 15 species among the males. Most of the
      males match the species as delimited by females. Both markers reveal cryptic
      species in P. quadrisetosa on Ficus vasculosa. Most species of wasps live on one
      species of fig but three species co-occur in two hosts (F. microcarpa and F.
      benjamina), which indicates host switching.

PMID- 22372853
TI  - Unifying prolonged copper exposure, accumulation, and toxicity from food and
      water in a marine fish.
AB  - The link between metal exposure and toxicity is complicated by numerous factors
      such as exposure route. Here, we exposed a marine fish (juvenile blackhead
      seabream Acanthopagrus schlegelii schlegelii) to copper either in a commercial
      fish diet or in seawater. Copper concentrations in intestine/liver were
      correlated linearly with influx rate, but appeared to be less influenced by
      uptake pathway (waterborne or dietary exposure). Influx rate best predicted Cu
      accumulation in the intestine and liver. However, despite being a good predictor
      of mortality within each pathway, influx rate was not a good predictor of
      mortality across both exposure pathways, as waterborne Cu caused considerably
      higher mortality than dietary Cu at a given influx rate. We show that the use of
      gill Cu accumulation irrespective of the exposure route as a model for observed
      fish mortality provided a clear relationship between accumulation and toxicity.
      Investigation of gill Cu accumulation may shed light on the different
      accumulation strategies from the two exposure pathways. This correlation offers
      potential for the use of branchial Cu concentration as an indicator of long-term
      Cu toxicity, allowing for differences in the relative importance of the uptake
      pathways in different field situations.

PMID- 22372855
TI  - Mechanical properties of polyamide versus different PMMA denture base materials.
AB  - PURPOSE: Polymethyl methacrylate (PMMA) resins are the most commonly used denture
      materials; however, they do not have a high flexural strength (FS). This study
      aimed to compare the mechanical properties of a polyamide-based, injection-molded
      denture material (Deflex) with another injection-molded PMMA base material (SR
      Ivocap) and a conventional compression-molded PMMA (Meliodent). MATERIALS AND
      METHODS: Flexural properties (deflection, bending strength, and bending modulus)
      of denture base materials were evaluated (n = 10). Specimens meeting
      International Standards Organization (ISO) specification number 20795-1
      requirements were prepared (65 * 10 * 3 mm(3)). A three-point bending test was
      carried out on an Instron testing machine at a 5 mm/min crosshead speed. The
      Knoop hardness test was used to compare microhardness values. Data were analyzed
      using ANOVA, followed by REGWQ. RESULTS: The group results, standard deviations,
      and statistical differences (p < 0.01) for Deflex, SR-Ivocap, and Meliodent were
      (A) flexural strength (MPa: 78.3 +/- 1.0,(a) 69.8 +/- 1.4,(b) 81.1 +/- 1(a)), (B)
      flexural modulus (GPa: 0.70 +/- 0.13,(a) 0.85 +/- 0.27,(a) 1.70 +/- 0.23(b)), (C)
      Knoop Hardness (kg/cm(2) : 7.5 +/- 1.0,(a) 13.5 +/- 1.4,(b) 16.9 +/- 1.0(c)).
      Different superscript letters indicate significant difference. All Meliodent
      specimens fractured during flexural testing, but no Deflex specimens did.
      CONCLUSIONS: While polyamide denture material produced good fracture resistance,
      its modulus is not yet sufficiently high to be equal to standard PMMA materials.
      Clinical Implications. Polyamide has some attractive advantages, but will require
      modification to produce consistently better properties than current PMMA
      materials.

PMID- 22372854
TI  - TcdB from hypervirulent Clostridium difficile exhibits increased efficiency of
      autoprocessing.
AB  - TcdB, an intracellular bacterial toxin that inactivates small GTPases, is a major
      Clostridium difficile virulence factor. Recent studies have found that TcdB
      produced by emerging/hypervirulent strains of C. difficile is more potent than
      TcdB from historical strains, and in the current work, studies were performed to
      investigate the underlying mechanisms for this change in TcdB toxicity. Using a
      series of biochemical analyses we found that TcdB from a hypervirulent strain
      (TcdB(HV) ) was more efficient at autoprocessing than TcdB from a historical
      strain (TcdB(HIST) ). TcdB(HV)  and TcdB(HIST)  were activated by similar
      concentrations of IP6; however, the overall efficiency of processing was 20%
      higher for TcdB(HV) . Using an activity-based fluorescent probe (AWP19) an
      intermediate, activated but uncleaved, form of TcdB(HIST)  was identified, while
      only a processed form of TcdB(HV)  could be detected under the same conditions.
      Using a much higher concentration (200 uM) of the probe revealed an activated
      uncleaved form of TcdB(HV) , indicating a preferential and more efficient
      engagement of intramolecular substrate than TcdB(HIST) . Furthermore, a peptide
      based inhibitor (Ac-GSL-AOMK) was found to block the cytotoxicity of TcdB(HIST) 
      at a lower concentration than required to inhibit TcdB(HV) . These findings
      suggest that TcdB(HV)  may cause increased cytotoxicity due to more efficient
      autoprocessing.

PMID- 22372856
TI  - Polyphosphate elicits pro-inflammatory responses that are counteracted by
      activated protein C in both cellular and animal models.
AB  - BACKGROUND: Recent results have indicated that polyphosphate, released by
      activated platelets, can function as a procoagulant to modulate the proteolytic
      activity of serine proteases of the blood clotting cascade. OBJECTIVE: To
      determine whether polyphosphate is involved in inducing signal transduction in
      cellular and animal models. METHODS: The effect of polyphosphate on human
      umbilical vein endothelial cells was examined by monitoring cell permeability,
      apoptosis and activation of NF-kappaB after treating cells with different
      concentrations of polyphosphate. Moreover, the expression of cell surface
      adhesion molecules (VCAM-1, ICAM-1 and E-selectin) and the adhesion of THP-1
      cells to polyphosphate-treated cells were monitored using established methods. In
      the in vivo model, the pro-inflammatory effect of polyphosphate was assessed by
      monitoring vascular permeability and migration of leukocytes to the peritoneal
      cavity of mice injected with polyphosphate. RESULTS: Polyphosphate, comprised of
      45, 65 and 70 phosphate units, enhanced the barrier permeability and apoptosis in
      cultured endothelial cells and up-regulated the expression of cell adhesion
      molecules, thereby mediating the adhesion of THP-1 cells to polyphosphate-treated
      endothelial cells. These effects of polyphosphate were mediated through the
      activation of NF-kappaB and could not be recapitulated by another anionic
      polymer, heparin. Polyphosphate also increased the extravasation of the bovine
      serum albumin (BSA)-bound Evans blue dye and the migration of leukocytes to the
      mouse peritoneal cavity, which was prevented when activated protein C (APC) was
      intravenously (i.v.) injected 2 h before the challenge. CONCLUSION:
      Polyphosphate, in addition to up-regulation of coagulation, can elicit potent pro
      inflammatory responses through the activation of NF-kappaB, possibly contributing
      to the pro-inflammatory effect of activated platelets.

PMID- 22372858
TI  - Drops sitting on a tilted plate: receding and advancing pinning.
AB  - The wetting behavior of a liquid drop sitting on an inclined plane is
      investigated experimentally and theoretically. Using Surface Evolver, the
      numerical simulations are performed based on the liquid-induced defect model, in
      which only two thermodynamic parameters (solid-liquid interfacial tensions before
      and after wetting) are required. A drop with contact angle (CA) equal to theta is
      first placed on a horizontal plate, and then the plate is tilted. Two cases are
      studied: (i) theta is adjusted to the advancing CA (theta(a)) before tilting, and
      (ii) theta is adjusted to the receding CA (theta(r)) before tilting. In the first
      case, the uphill CA declines and the downhill CA remains unchanged upon
      inclination. When the tilted drop stays at rest, the pinning of the receding part
      of the contact line (receding pinning) and the depinning of the advancing part of
      the contact line (advancing depinning) are observed. The free energy analysis
      reveals that upon inclination, the reduction of the solid-liquid free energy
      dominates over the increment of the liquid-gas free energy associated with shape
      deformation. In the second case, the downhill CA grows and the uphill CA remains
      the same upon inclination. Advancing pinning and receding depinning are noted for
      the tilted drop at rest. The free energy analysis indicates that upon
      inclination, the decrease of the liquid-gas free energy compensates the increment
      of the solid-liquid free energy. The experimental results are in good agreement
      with those of simulations.

PMID- 22372857
TI  - Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration
      in the developing mouse brain.
AB  - GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic
      neurodegeneration in 7-day-old mice. A small but a significant increase observed
      2 h after ethanol exposure was followed by a marked increase around 24 h.
      Subcellular fractionation of the brain 24 h after ethanol treatment indicated
      that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well
      as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain.
      Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong
      punctate staining mainly in activated microglia, in which it partially overlapped
      with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was
      weaker neuronal staining, which partially co-localized with complex IV, a
      mitochondrial marker, and was augmented in cleaved caspase 3-positive neurons. In
      contrast, the control brain showed only faint and diffuse GM2 staining in
      neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced
      cytochrome c release in a manner similar to that of GD3 ganglioside. Because
      ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c
      release and caspase 3 activation in the 7-day-old mouse brain, the GM2 elevation
      in mitochondria may be relevant to neuroapoptosis. Subsequently, activated
      microglia accumulated GM2, indicating a close relationship between GM2 and
      ethanol-induced neurodegeneration.

PMID- 22372859
TI  - Assessment of predictive models for chlorophyll-a concentration of a tropical
      lake.
AB  - BACKGROUND: This study assesses four predictive ecological models; Fuzzy Logic
      (FL), Recurrent Artificial Neural Network (RANN), Hybrid Evolutionary Algorithm
      (HEA) and multiple linear regressions (MLR) to forecast chlorophyll- a
      concentration using limnological data from 2001 through 2004 of unstratified
      shallow, oligotrophic to mesotrophic tropical Putrajaya Lake (Malaysia).
      Performances of the models are assessed using Root Mean Square Error (RMSE),
      correlation coefficient (r), and Area under the Receiving Operating
      Characteristic (ROC) curve (AUC). Chlorophyll-a have been used to estimate algal
      biomass in aquatic ecosystem as it is common in most algae. Algal biomass
      indicates of the trophic status of a water body. Chlorophyll- a therefore, is an
      effective indicator for monitoring eutrophication which is a common problem of
      lakes and reservoirs all over the world. Assessments of these predictive models
      are necessary towards developing a reliable algorithm to estimate chlorophyll- a
      concentration for eutrophication management of tropical lakes. RESULTS: Same data
      set was used for models development and the data was divided into two sets;
      training and testing to avoid biasness in results. FL and RANN models were
      developed using parameters selected through sensitivity analysis. The selected
      variables were water temperature, pH, dissolved oxygen, ammonia nitrogen, nitrate
      nitrogen and Secchi depth. Dissolved oxygen, selected through stepwise procedure,
      was used to develop the MLR model. HEA model used parameters selected using
      genetic algorithm (GA). The selected parameters were pH, Secchi depth, dissolved
      oxygen and nitrate nitrogen. RMSE, r, and AUC values for MLR model were (4.60,
      0.5, and 0.76), FL model were (4.49, 0.6, and 0.84), RANN model were (4.28, 0.7,
      and 0.79) and HEA model were (4.27, 0.7, and 0.82) respectively. Performance
      inconsistencies between four models in terms of performance criteria in this
      study resulted from the methodology used in measuring the performance. RMSE is
      based on the level of error of prediction whereas AUC is based on binary
      classification task. CONCLUSIONS: Overall, HEA produced the best performance in
      terms of RMSE, r, and AUC values. This was followed by FL, RANN, and MLR.

PMID- 22372860
TI  - Diagnosis of tuberculous lymphadenitis using fine needle aspiration biopsy.
AB  - BACKGROUND: Tuberculous lymphadenitis is the commonest form of extrapulmonary
      tuberculosis. However, the optimal approach to diagnosis, employing biopsy by
      either fine needle aspiration (FNA) or surgical excision, remains uncertain.
      AIMS: To evaluate the diagnostic value of biopsy using each of the component
      diagnostic modalities of FNA (microscopy, cytology and culture), and compare
      these with excision biopsy in the diagnosis of tuberculous lymphadenitis in a
      predominantly migrant population in Melbourne. METHODS: A retrospective
      examination of tuberculous lymphadenitis cases presenting to Western Health over
      12 years was conducted. Using a reference method of positive culture of
      Mycobacterium tuberculosis, the diagnostic sensitivities of each modality
      employed in FNA were determined. RESULTS: Forty-two subjects having FNA and 30
      having excision biopsy as the initial investigation were compared. Among
      specimens obtained by FNA, sensitivity of microscopy was 18% (95% confidence
      interval (CI): 5-40%) and sensitivity of cytology was 38% (95% CI: 20-59%). For
      specimens obtained by excision biopsies, sensitivities for microscopy and
      histology were 17% (95% CI: 2-32%) and 96% (95% CI: 88-100%) respectively.
      Sensitivity of culture performed on FNA specimens was 86% (95% CI: 65-97%).
      CONCLUSIONS: Given the relatively high sensitivity of mycobacterial cultures from
      FNA, this study supports its routine use as the initial investigation in most
      patients with suspected tuberculous lymphadenitis. Microscopy and cytology add
      relatively little to the clinical utility of FNA

PMID- 22372862
TI  - Measurement of peri-prostatic fat thickness using transrectal ultrasonography
      (TRUS): a new risk factor for prostate cancer.
AB  - Study Type - Prognosis (cohort) Level of Evidence 2b. What's known on the
      subject? and What does the study add? ADIPOSE tissue secretes various endocrine
      and paracrine mediators. Some authors have begun to consider whether peri
      prostatic fat (PPF) may interact with the prostate and play a role in
      carcinogenesis. It has recently been shown that the PPF quantity measured by CT
      is associated with more aggressive disease in patients undergoing radiation
      therapy. Our group studied a population not yet diagnosed with prostate cancer.
      By doing so we were able to identify PPF thickness on transrectal ultrasonography
      as a risk factor for prostate cancer detection upon biopsy, and as a risk factor
      for high-grade disease. Our study also raises interesting questions about the
      underlying mechanisms of the association between PPF quantity and prostate
      cancer. OBJECTIVE: To determine if the amount of peri-prostatic fat (PPF) on
      transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer
      overall and high-grade prostate cancer (Gleason >=4). PATIENTS AND METHODS: A
      prospectively maintained database of patients undergoing prostate biopsy at
      Princess Margaret Hospital for cancer suspicion was used. * All TRUS examinations
      were retrospectively reviewed upon 'blinding' to outcome. * PPF thickness,
      measured as the distance between the prostate and the pubic bone, was used as an
      index of the quantity of PPF. * PPF measurements, together with other prostate
      cancer risk factors, were evaluated against prostate cancer and high-grade
      prostate cancer detection upon biopsy with univariable and multivariable logistic
      regression and area under the receiver operating characteristic curve (AUC)
      analysis. RESULTS: Of the 931 patients, 434 (47%) were diagnosed with prostate
      cancer and 218 (23%) were diagnosed with high-grade prostate cancer. * The mean
      (range) PPF thickness was 5.3 (0-15) mm. * Increasing PPF thickness was
      associated with prostate cancer and high-grade prostate cancer diagnosis, with
      graded effect. When adjusting for other variables, the odds of detecting any
      prostate cancer and high-grade prostate cancer increased 12% (odds ratio [OR]
      1.12, 95% confidence interval [CI] 1.02-1.23) and 20% (OR 1.20, 95% CI 1.07
      1.34), respectively, for each millimetre increase in PPF thickness. * The AUCs
      for the association of PPF with prostate cancer and high-grade prostate cancer
      were 0.58 (95% CI 0.54-0.62) and 0.59 (95% CI 0.55-0.64), respectively.
      CONCLUSION: The amount of PPF can be estimated with TRUS and is a predictor of
      prostate cancer and high-grade prostate cancer at biopsy. To our knowledge, this
      study is the first to investigate PPF quantity in patients without prior prostate
      cancer diagnosis.

PMID- 22372863
TI  - Species distribution models as a tool to estimate reproductive parameters: a case
      study with a passerine bird species.
AB  - 1. Correlative species distribution models (SDMs) assess relationships between
      species distribution data and environmental features, to evaluate the
      environmental suitability (ES) of a given area for a species, by providing a
      measure of the probability of presence. If the output of SDMs represents the
      relationships between habitat features and species performance well, SDM results
      can be related also to other key parameters of populations, including
      reproductive parameters. To test this hypothesis, we evaluated whether SDM
      results can be used as a proxy of reproductive parameters (breeding output,
      territory size) in red-backed shrikes (Lanius collurio). 2. The distribution of
      726 shrike territories in Northern Italy was obtained through multiple focused
      surveys; for a subset of pairs, we also measured territory area and number of
      fledged juveniles. We used Maximum Entropy modelling to build a SDM on the basis
      of territory distribution. We used generalized least squares and spatial
      generalized mixed models to relate territory size and number of fledged juveniles
      to SDM suitability, while controlling for spatial autocorrelation. 3. Species
      distribution models predicted shrike distribution very well. Territory size was
      negatively related to suitability estimated through SDM, while the number of
      fledglings significantly increased with the suitability of the territory. This
      was true also when SDM was built using only spatially and temporally independent
      data. 4. Results show a clear relationship between ES estimated through presence
      only SDMs and two key parameters related to species' reproduction, suggesting
      that suitability estimated by SDM, and habitat quality determining reproduction
      parameters in our model system, are correlated. Our study shows the potential use
      of SDMs to infer important fitness parameters; this information can have great
      importance in management and conservation.

PMID- 22372864
TI  - Synthesis and biological evaluation of pyrimidine-based dual inhibitors of human
      epidermal growth factor receptor 1 (HER-1) and HER-2 tyrosine kinases.
AB  - A novel series of N(4)-(3-chlorophenyl)-5-(oxazol-2-yl)pyrimidine-4,6-diamines
      were synthesized and evaluated as dual inhibitors of HER-1/HER-2 tyrosine
      kinases. In contrast to the currently approved HER-2-targeted agent (lapatinib,
      1), our irreversible HER-1/HER-2 inhibitors have the potential to overcome the
      clinically relevant and mutation-induced drug resistance. The selected compound
      (19a) showed excellent inhibitory activity toward HER-1/HER-2 tyrosine kinases
      with selectivity over 20 other kinases and inhibited the proliferation of both
      cancer cell types: lapatinib-sensitive cell lines (SK-Br3, MDA-MB-175, and N87)
      and lapatinib-resistant cell lines (MDA-MB-453, H1781, and H1975). The excellent
      pharmacokinetic profiles of 19a in mice and rats led us to further investigation
      of a novel therapeutic agent for HER-2-targeting treatment of solid tumors,
      especially HER-2-positive breast/gastric cancer and HER-2-mutated lung cancer.

PMID- 22372865
TI  - Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of
      metformin hydrochloride.
AB  - Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in
      obese patients. It is well absorbed from the upper part of gastrointestinal tract
      and has oral bioavailability of 50% to 60%. The objective of this study was to
      formulate MH into floating microspheres in order to increase its residence time
      at the site of absorption and thus improve its bioavailability; and to extend the
      duration of action along with possibilities of dose reduction. Microspheres were
      prepared by emulsion solvent evaporation method and evaluated for particle size,
      entrapment efficiency, buoyancy, and in vitro release; and further characterized
      by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning
      electron microscopy, and differential scanning calorimetry. The pharmacokinetic
      and pharmacodynamic evaluation of selected formulation was carried out in male
      Wistar diabetic rats. The data was statistically analyzed by unpaired t-test. A
      3.5-fold increase in relative bioavailability was observed. The prolongation of
      half-life (t(1/2)) from 4.5 +/- 2.41 h to 14.12 +/- 4.81 h indicated extended
      duration of action. Oral glucose tolerance test (OGTT) was analyzed by one-way
      analysis of variance followed by Dunnet multiple comparison test, a significant
      decrease (p < 0.05) in the blood glucose levels was observed when formulations
      were compared with control rats. Hence, MH floating microspheres were tested at
      50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p
      >0.05). In conclusion, an effective oral antidiabetics treatment can be achieved
      by formulating MH into floating microspheres which results in increase in
      bioavailability along with extended duration of action resulting in possible
      reduction in dose.

PMID- 22372866
TI  - A prediction model of histological chorioamnionitis and funisitis in preterm
      prelabor rupture of membranes: analyses of multiple proteins in the amniotic
      fluid.
AB  - OBJECTIVE: To determine the best prediction model of histological
      chorioamnionitis and funisitis in preterm prelabor rupture of membranes (PPROM)
      using selected candidate proteins in the amniotic fluid (AF). MATERIAL AND
      METHODS: Prospective cohort study. Twenty-six AF proteins were assayed by a
      multiple immunoassay from 107 women with membranes rupture from 23+0 to 36+6
      weeks. The Czech Republic policy is active management, and the majority of women
      were delivered within 72 h after the rupture of membranes, except for women with
      PPROM <28+0 weeks who were managed conservatively. The best predictive models to
      diagnose histological chorioamnionitis and funisitis were calculated by logistic
      regression depending on the gestational age (GA) at membrane rupture. RESULTS:
      Both IL-6 and a combination of IL-10, and migration inhibiting factor (MIF) were
      the best predictive models of histological chorioamnionitis and funisitis,
      respectively, with sensitivity, specificity, positive and negative predictive
      values and positive likelihood ratio (LR+) of 62, 83, 37, 93 and 3.6 and of 63,
      91, 53, 94 and 7.0, respectively. Depending on whether GA at membrane rupture was
      <32 or >= 32 weeks, IL-10, alone or in combination with MIF and triggering
      receptor expressed on myeloid cells-1, was the strongest inflammatory biomarker
      for funisitis (LR+10.6 and 36.6, respectively). CONCLUSION: Regardless of the GA
      at membrane rupture, IL-6 from the AF was the best predictor of histological
      chorioamnionitis. Amniotic fluid IL-10 was notably accurate in the prediction of
      funisitis.

PMID- 22372867
TI  - Use of radiolabeled compounds in drug metabolism and pharmacokinetic studies.
AB  - As part of the drug discovery and development process, it is important to
      understand the fate of the drug candidate in humans and the relevance of the
      animal species used for preclinical toxicity and pharmacodynamic studies.
      Therefore, various in vitro and in vivo studies are conducted during the
      different stages of the drug development process to elucidate the absorption,
      distribution, metabolism, and excretion properties of the drug candidate.
      Although state-of-the-art LC/MS techniques are commonly employed for these
      studies, radiolabeled molecules are still frequently required for the
      quantification of metabolites and to assess the retention and excretion of all
      drug related material without relying on structural information and MS ionization
      properties. In this perspective, we describe the activities of Isotope Chemistry
      at AstraZeneca and give a brief overview of different commonly used approaches
      for the preparation of (14)C- and (3)H-labeled drug candidates. Also various drug
      metabolism and pharmacokinetic studies utilizing radiolabeled drug candidates are
      presented with in-house examples where relevant. Finally, we outline strategic
      changes to our use of radiolabeled compounds in drug metabolism and
      pharmacokinetic studies, with an emphasis on delaying of in vivo studies
      employing radiolabeled drug molecules.

PMID- 22372868
TI  - Are primary care providers offering HIV testing to patients in a predominantly
      Hispanic community health center? An exploratory study.

PMID- 22372869
TI  - Quality of life in newly diagnosed children with specific learning disabilities
      (SpLD) and differences from typically developing children: a study of child and
      parent reports.
AB  - INTRODUCTION: Research on quality of life (QoL) of school children with specific
      learning disabilities (SpLD) and their parents is scarce. The present study
      explores QoL deficits in newly diagnosed children with SpLD and their parents, in
      comparison to a similar age group of typically developing children. Possible
      associations between parental and child QoL were statistically explored in both
      groups of children. METHODS: 70 newly diagnosed children with SpLD [International
      Classification of Diseases-10 (ICD-10) criteria] (38 boys, 32 girls, mean age
      10.1 years) and a control group of 69 typically developing children of the same
      age (40 boys, 29 girls, mean age 10.6 years) were recruited. Children were of
      normal intelligence quotient, attending mainstream schools. Their parents were
      also recruited so a child's scores could be associated with corresponding
      parental scores (mother or father). Children's QoL was assessed by the German
      questionnaire for measuring quality of life in children and adolescents (KINDL(R)
      ) questionnaire and parental QoL by World Health Organization Quality of Life
      brief questionnaire (WHOQOL-BREF) of the World Health Organization. RESULTS:
      Children with SpLD in comparison to typically developing children reported
      according to the KINDL(R) measurement poorer emotional well-being, lower self
      esteem and satisfaction in their relationships with family and friends.
      Surprisingly, school functioning was not reported by these children as an area of
      concern. Parents of children with SpLD indicated experiencing lower satisfaction
      in the WHOQOL-BREF domains of social relationships and environment. Correlational
      and regression analysis with parental-child QoL scores provided evidence that in
      the SpLD group, parental scores on WHOQOL-BREF social relationships and
      psychological health domains could be predictors of the child's emotional well
      being, satisfaction with family, friends and school functioning. Stepwise
      regression analysis verified the effect of parents' WHOQOL-BREF social
      relationships domain on several dimensions of children's KINDL(R) QoL.
      CONCLUSIONS:   The results may suggest certain significant effects of the SpLD
      condition on newly diagnosed children's QoL. Emotional and social deficits seem
      to be experienced by this cohort of children and their parents. Investigation
      into the possible interrelationships between parental and child QoL seems to
      indicate that parental social wellbeing may to a certain extend influence some
      dimensions of the child's QoL. The findings are useful for policy making and
      specialized interventions for children with SpLD and their families.

PMID- 22372870
TI  - The ability of cone-beam computed tomography to detect simulated buccal and
      lingual recesses in root canals.
AB  - AIM: To compare the ability of cone-beam computed tomography (CBCT) and digital
      periapical radiographs (PR) to detect simulated tissue-occupied recesses in root
      canals. METHODOLOGY: A standard canal was created in 30 extracted mandibular
      premolar roots. Each root was longitudinally split into buccal and lingual
      halves. In 20 teeth, a standard groove, 4mm in length, 0.5mm deep and 0.3mm wide,
      was prepared on each root half and filled with radiolucent plasticine (a
      modelling clay), simulating tissue-occupied buccal and lingual recesses. In the
      other 10 teeth, no grooves were cut. Each root was reassembled and filled with
      laterally compacted gutta-percha and sealer. PR and CBCT were used to detect the
      plasticine-filled grooves. The images were pooled and blindly evaluated by three
      calibrated examiners (A, B and C). A chi-square test was used to analyse the
      data. RESULTS: Examiner A, B, C detected grooves on CBCT scans in 20, 20 and 23
      teeth, respectively, of which 19, 18 and 19 were true positives. The accuracy of
      CBCT in diagnosing plasticine-filled grooves was 82-92% for three examiners,
      significantly higher than the accuracy of PR (30-33%; P<0.001). CONCLUSIONS: Cone
      beam computed tomography accurately detected simulated tissue-occupied buccal and
      lingual recesses.

PMID- 22372871
TI  - Preparation and in vitro evaluation of a folate-linked liposomal curcumin
      formulation.
AB  - Curcumin (CUR), a plant-derived compound, exhibits versatile antitumor effects.
      However, its poor hydrophilic property limits its application. To circumvent
      these drawbacks, we encapsulated CUR in liposomes modified with folic acid for
      better solubility and enhanced tumor targeting. This novel formulation was
      prepared by a film-dispersion method and characterized by size, zeta potential,
      drug-loading efficiency, and physical-condition stability. In vitro, cellular
      uptake efficiency, cytotoxicity, and apoptosis analysis by flow cytometry were
      performed to evaluate tumor targeting and killing ability. Results showed that
      the folate-receptor (FR)-targeted liposomal CUR (F-CUR-L) performed with improved
      solubility, sufficient stability, and enhanced antitumor activity. Mean diameter,
      zeta potential, and drug-loading efficiency were 182 nm, -26 mV, and 68%,
      respectively, and this formulation exhibited stability in storage at 4  degrees C
      for 1 month. In vitro, FR-positive cells endocytosed more F-CUR-L than
      nontargeted liposomal CUR (CUR-L); thus, the former induced more cellular
      proliferation inhibition and higher apoptosis than the latter, and the enhanced
      targeting could be hindered by 1 mM of free folic acid. Further, KB cells were
      more sensitive to F-CUR-L, compared to Hela cells. Finally, the two kinds of
      tumor cells treated with F-CUR-L also showed dose- and time-dependent apoptosis.

PMID- 22372872
TI  - Heartmate IITM device placement five years following ACORN CorCapTM device
      implantation.
AB  - Left ventricular assist device (LVAD) for destination therapy (DT) is an
      established therapy. More patients requiring LVADs have had prior open heart
      surgery, the majority of whom had prior sternotomy. As such, placement of an
      implantable LVAD in a redo setting can be hazardous. This report describes the
      implant of a Heartmate IITM LVAD in a patient with a prior ACORN CorCapTM.

PMID- 22372873
TI  - Validation of an automated procedure to isolate human adipose tissue-derived
      cells by using the Sepax(r) technology.
AB  - The stromal vascular fraction of adipose tissue has gained popularity as a source
      of autologous progenitor cells for tissue engineering and regenerative medicine
      applications. The aim of this study was to validate a newly developed, automated
      procedure to isolate adipose-derived mesenchymal stem/stromal cells (ASCs) from
      adult human lipoaspirates in a closed and clinical-grade device, based on the
      Sepax((r)) technology. Using a total of 11 donors, this procedure was compared
      with the standard operator-based manual separation in terms of isolation yield,
      clonogenic fraction, phenotype, and differentiation potential of ASCs. As
      compared with the manual process, automation resulted in a 62% higher isolation
      yield, with 2.6+/-1.2*10(5) nucleated cells per mL of liposuction, and a 24%
      higher frequency of clonogenic progenitors. The variability in the isolation
      yield and clonogenicity across different preparations was reduced by 18% and 50%,
      respectively. The cytofluorimetric profile and in vitro differentiation capacity
      into mesenchymal lineages were comparable in the cells isolated using the two
      procedures. The new Sepax-based process thus allows an efficient isolation of
      ASCs with higher and more reproducible yields than the standard manual procedure,
      along with minimal operator intervention. These results are expected to
      facilitate the use of ASCs for clinical purposes, either within an intraoperative
      setting or in combination with further in vitro cell expansion/cultivation.

PMID- 22372874
TI  - Assessing the effect of humic acid redox state on organic pollutant sorption by
      combined electrochemical reduction and sorption experiments.
AB  - Natural Organic Matter (NOM) is a major sorbent for organic pollutants in soils
      and sediments. While sorption under oxic conditions has been well investigated,
      possible changes in the sorption capacity of a given NOM induced by reduction
      have not yet been studied. Reduction of quinones to hydroquinones, the major
      redox active moieties in NOM, increases the number of H-donor moieties and thus
      may affect sorption. This work compares the sorption of four nonionic organic
      pollutants of different polarities (naphthalene, acetophenone, quinoline, and 2
      naphthol), and of the organocation paraquat to unreduced and electrochemically
      reduced Leonardite Humic Acid (LHA). The redox states of reduced and unreduced
      LHA in all sorption experiments were stable, as demonstrated by a
      spectrophotometric 2,6-dichlorophenol indophenol reduction assay. The sorption
      isotherms of the nonionic pollutants were highly linear, while paraquat sorption
      was strongly concentration dependent. LHA reduction did not result in significant
      changes in the sorption of all tested compounds, not even of the cationic
      paraquat at pH 7, 9, and 11. This work provides the first evidence that changes
      in NOM redox state do not largely affect organic pollutant sorption, suggesting
      that current sorption models are applicable both to unreduced and to reduced soil
      and sediment NOM.

PMID- 22372875
TI  - Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma
      cell death.
AB  - Induction of apoptotic cell death in response to chemotherapy and other external
      stimuli has proved extremely difficult in melanoma, leading to tumor progression,
      metastasis formation and resistance to therapy. A promising approach for cancer
      chemotherapy is the inhibition of proteasomal activity, as the half-life of the
      majority of cellular proteins is under proteasomal control and inhibitors have
      been shown to induce cell death programs in a wide variety of tumor cell types. 4
      Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has
      already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was
      able to induce the accumulation of ubiquitinated proteins, including classic
      targets of this process such as Mcl-1. As shown for other proteasomal inhibitors
      in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro
      apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We
      demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an
      artificial skin model containing melanoma also provided evidence that 4-NC
      prevented melanoma proliferation in a 3D model that more closely resembles normal
      human skin.

PMID- 22372876
TI  - A technique for impressing the severely resorbed mandibular edentulous ridge.
AB  - Patients presenting with severe resorption of the residual alveolar ridges are
      relatively common today in both private practices and teaching institutions. The
      severely resorbed mandibular ridge is more challenging to impress than is the
      maxillary ridge. Accurately capturing the denture-bearing surface in its entirety
      is crucial to providing the patient with a functionally successful prosthesis.
      This article presents a technique to overcome the difficulties encountered in
      impressing the severely resorbed mandibular ridge using elastomeric impression
      materials and a modified special custom tray.

PMID- 22372877
TI  - Cytocompatibility of porous biphasic calcium phosphate granules with human
      mesenchymal cells by a multiparametric assay.
AB  - This work aims to evaluate the cytocompatibility of injectable and moldable
      restorative biomaterials based on granules of dense or porous biphasic calcium
      phosphates (BCPs) with human primary mesenchymal cells, in order to validate them
      as tools for stem cell-induced bone regeneration. Porous hydroxyapatite (HA) and
      HA/beta-tricalcium phosphate (beta-TCP) (60:40) granules were obtained by the
      addition of wax spheres and pressing at 20 MPa, while dense materials were
      compacted by pressing at 100 MPa, followed by thermal treatment (1100 degrees C),
      grinding, and sieving. Extracts were prepared by 24-h incubation of granules on
      culture media, with subsequent exposition of human primary mesenchymal cells.
      Three different cell viability parameters were evaluated on the same samples.
      Scanning electron microscopy analysis of the granules revealed distinct dense and
      porous surfaces. After cell exposition to extracts, no significant differences on
      mitochondrial activity (2,3-bis(2-methoxy-4-nitro-5-sulfophenly)-5-[(phenylamino)
      carbonyl]-2H-tetrazolium hydroxide) or cell density (Crystal Violet Dye Elution)
      were observed among groups. However, Neutral Red assay revealed that dense
      materials extracts induced lower levels of total viable cells to porous HA/beta
      TCP (P < 0.01). Calcium ion content was also significantly lower on the extracts
      of dense samples. Porogenic treatments on BCP composites do not affect
      cytocompatibility, as measured by three different parameters, indicating that
      these ceramics are well suited for further studies on future bioengineering
      applications.

PMID- 22372878
TI  - New anatomical landmarks to study the relationship between fetal lung area and
      thoracic circumference by three-dimensional ultrasonography.
AB  - OBJECTIVE: To evaluate the relation between total lung area (TLA) and thoracic
      circumference (TC) ratio by three-dimensional (3D) ultrasonography applying new
      anatomical landmarks as the fetal aorta and inferior angle of the scapula.
      METHODS: A longitudinal prospective study was conducted with 56 uncomplicated
      pregnancies between 24 and 32 weeks of gestation. Polynomial regressions were
      used to evaluate the correlation between TC and gestational age (GA) as well as
      TC and estimated fetal weight (EFW). A simple linear regression was used to
      evaluate the correlation between TLA and Total thoracic area (TTA) and GA. The
      intraclass correlation coefficient (ICC) was used to assess the intra and
      interobserver variability. RESULTS: 127 examinations were performed. TC values
      ranged from 150 to 174 mm (mean 166 mm) at 24 weeks and 215-248 mm (mean 231 mm)
      at 32 weeks. The TLA/TC ratio ranged from a mean of 0.64 at 24 weeks (range 0.56
      0.70) to 0.90 at 32 weeks gestation (range 0.79-1.01). The intraobserver
      variability using the ICC was of 0.919 for TC; 0.916 for TTA; 0.860 for right
      lung area (RLA) and 0.910 for left lung area (LLA). Interobserver reproducibility
      was with an ICC of 0.970 for TC; 0.984 for RLA and 0.910 for LLA. CONCLUSIONS:
      Measurement of fetal TC and the relationship between TLA and TC by 3D
      ultrasonography applying new anatomical landmarks shows good reproducibility and
      allows a new assessment of thoracic and lung growth.

PMID- 22372885
TI  - Estimating partial observability and nonlinear climate effects on stochastic
      community dynamics of migratory waterfowl.
AB  - 1. Understanding the impact of environmental variability on migrating species
      requires the estimation of sequential abiotic effects in different geographic
      areas across the life cycle. For instance, waterfowl (ducks, geese and swans)
      usually breed widely dispersed throughout their breeding range and gather in
      large numbers in their wintering headquarters, but there is a lack of knowledge
      on the effects of the sequential environmental conditions experienced by
      migrating birds on the long-term community dynamics at their wintering sites. 2.
      Here, we analyse multidecadal time-series data of 10 waterfowl species wintering
      in the Guadalquivir Marshes (SW Spain), the single most important wintering site
      for waterfowl breeding in Europe. We use a multivariate state-space approach to
      estimate the effects of biotic interactions, local environmental forcing during
      winter and large-scale climate during breeding and migration on wintering
      multispecies abundance fluctuations, while accounting for partial observability
      (observation error and missing data) in both population and environmental data.
      3. The joint effect of local weather and large-scale climate explained 31.6% of
      variance at the community level, while the variability explained by interspecific
      interactions was negligible (<5%). In general, abiotic conditions during winter
      prevailed over conditions experienced during breeding and migration. Across
      species, a pervasive and coherent nonlinear signal of environmental variability
      on population dynamics suggests weaker forcing at extreme values of abiotic
      variables. 4. Modelling missing observations through data augmentation increased
      the estimated magnitude of environmental forcing by an average 30.1% and reduced
      the impact of stochasticity by 39.3% when accounting for observation error.
      Interestingly however, the impact of environmental forcing on community dynamics
      was underestimated by an average 15.3% and environmental stochasticity
      overestimated by 14.1% when ignoring both observation error and data
      augmentation. 5. These results provide a salient example of sequential multiscale
      environmental forcing in a major migratory bird community, which suggests a
      demographic link between the breeding and wintering grounds operating through
      nonlinear environmental effects. Remarkably, this study highlights that modelling
      observation error in the environmental covariates of an ecological model can be
      proportionally more important than modelling this source of variance in the
      population data.

PMID- 22372886
TI  - Comparison of the marginal adaptation of zirconium dioxide crowns in preparations
      with two different finish lines.
AB  - PURPOSE: The purpose of this study was to evaluate the marginal adaptation of
      zirconium dioxide crowns in preparations with two different finish line
      configurations before and after porcelain firing cycles, after a glaze cycle, and
      after cementation. MATERIALS AND METHODS: Twenty human molar teeth were prepared
      to receive full crowns; ten were prepared with a 90 degrees  round shoulder and
      another ten with a 45 degrees  chamfer finish line. Zirconium dioxide copings
      were fabricated using CAD/CAM technology (LavaTM system). They were then veneered
      with a low-fusing glass-ceramic (IPS e.max(r) Ceram). Finally, they were glazed
      and cemented with a resin-composite cement (RelyXTM Unicem, AplicapTM).
      Measurements for marginal adaptation using stereomicroscopy (40*) were performed
      at four stages: copings (S1), after porcelain firing cycles (S2), after glazing
      (S3), and after cementation (S4). One-way ANOVA was used to assess the influence
      of the finish line design on the marginal adaptation in each stage. Two-way ANOVA
      with repeated measurements was performed to assess the influence on the marginal
      adaptation of the porcelain firing cycles, glaze firing cycle, and cementation.
      RESULTS: The measured marginal gap mean values for the shoulder group (MUm) were:
      50.13 (S1), 54.32 (S2), 55.12 (S3), and 59.83 (S4). The values for the chamfer
      group were: 63.56 (S1), 71.85 (S2), 74.12 (S3), and 76.97 (S4). When comparing
      marginal gaps between specimens with two different finish lines, differences were
      noticed at the four studied stages (p = 0.0165, p = 0.0027, p = 0.0009, and p =
      0.0009, respectively). No differences were manifested in the marginal gap
      measurements of the shoulder group at the different stages of fabrication (p =
      0.4335); however, in the chamfer group, differences were noticed between S1 and
      S3 (p = 0.0042). CONCLUSIONS: Marginal adaptation was influenced by the finish
      line design. The firing cycles significantly affected the chamfer group;
      nevertheless, the marginal gap was within the range of clinical acceptability.

PMID- 22372887
TI  - Simulation of cell seeding within a three-dimensional porous scaffold: a fluid
      particle analysis.
AB  - Cell seeding is a critical step in tissue engineering. A high number of cells
      evenly distributed in scaffolds after seeding are associated with a more
      functional tissue culture. Furthermore, high cell densities have shown the
      possibility to reduce culture time or increase the formation of tissue.
      Experimentally, it is difficult to predict the cell-seeding process. In this
      study, a new methodology to simulate the cell-seeding process under perfusion
      conditions is proposed. The cells are treated as spherical particles dragged by
      the fluid media, where the physical parameters are computed through a Lagrangian
      formulation. The methodology proposed enables to define the kinetics of cell
      seeding continuously over time. An exponential relationship was found to optimize
      the seeding time and the number of cells seeded in the scaffold. The cell
      distribution and cell efficiency predicted using this methodology were similar to
      the experimental results of Melchels et al. One of the main advantages of this
      method is to be able to determine the three-dimensional position of all the
      seeded cells and to, therefore, better know the initial conditions for further
      cell proliferation and differentiation studies. This study opens up the field of
      numerical predictions related to the interactions between biomaterials, cells,
      and dynamics media.

PMID- 22372888
TI  - Hospitalisation of high-care residents of aged care facilities: are goals of care
      discussed?
AB  - BACKGROUND: Residents of residential aged care facilities (RACF) are commonly
      hospitalised towards the end of life. Determining the hospitalisation
      experiences, including the discussion of goals of treatment, is essential to best
      plan care including planning for end-of-life care for this population. AIM: To
      document hospital presentation characteristics, course, outcomes and care
      planning for high-care residents of RACF. METHODS: A retrospective review of
      medical records was conducted for all high-care residents aged >64 years
      presenting to a metropolitan hospital over a 6-month period. RESULTS: One hundred
      and eighty-six high-care residents of RACF presented to hospital 228 times.
      Transfer paperwork documented resuscitation status for 49 (21%) presentations,
      and a medical enduring power of attorney or advanced care plan for 85 (37%).
      Patients had high rates of comorbidities (average Charlson comorbidity index
      score = 3), polypharmacy (93%), impaired mobility (89%), impaired cognition (81%)
      and incontinence (76%). Resuscitation status was documented in 50 (55%) and
      family discussion in 38 (42%) of 91 admissions exceeding 48 h. Documented family
      discussion was significantly associated with complications or new events
      occurring during admission (odds ratio 1.56, 95% confidence interval 1.07-2.26).
      CONCLUSION: There were low rates of documentation of resuscitation status or
      family discussion for this highly vulnerable population. Neither hospitals nor
      community providers appear to take responsibility for future care planning. Acute
      hospitals could play a greater role in care planning because discussion around
      course of illness and goals of treatment may enhance patient management,
      satisfaction and reduce hospitalisations.

PMID- 22372889
TI  - Synthesis and assessment of globotriose-chitosan conjugate, a novel inhibitor of
      shiga toxins produced by Escherichia coli.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) causes diarrhea and colitis
      in humans that can develop into a life-threatening hemolytic uremic syndrome
      (HUS). Developing efficient means of controlling STEC diseases, for which no
      drugs or vaccines are currently available, remains a high priority. We report
      here the construction and development of chitosan conjugates bearing the Stx
      ligand trisaccharide globotriose to demonstrate their potential as STEC disease
      treatment agents. The synthesis was accomplished by grafting a globotriose
      derivative containing an aldehyde-functionalized aglycone to chitosan amino
      groups. The obtained globotriose-chitosan conjugate bound with high affinity to
      Stx and efficiently neutralized its toxicity on Vero cells. Moreover, Stx levels
      in the gut of infected mice receiving oral doses of the conjugate were greatly
      diminished, enabling the mice to resist a fatal STEC challenge. The conjugate
      appears to function as a Stx adsorbent in the gut, preventing toxin entry into
      the bloodstream and consequent development of HUS. As such, the conjugate could
      act as a novel agent against STEC disease.

PMID- 22372890
TI  - Relationship between stent malapposition and incomplete neointimal coverage after
      drug-eluting stent implantation.
AB  - BACKGROUND: Using optical coherence tomography (OCT), we evaluated the
      relationship between malapposed and uncovered struts following implantation of
      drug-eluting stents (DESs). METHODS: A total of 271 patients with 306 lesions who
      underwent DES implantation and follow-up OCT were included in the study. The
      lesions were grouped based on the presence of malapposition and then by the
      median value of the percentage of malapposed struts (1.3%) to produce 3 groups:
      lesions without malapposition (group I, n = 232) and those with percentage of
      malapposed struts <1.3% (group II, n = 37) or >=1.3% (group III, n = 37).
      Percentages of malapposed and uncovered struts were calculated as percent ratio
      of malapposed or uncovered to total struts in the defined cross-sections,
      respectively. We compared percentage of uncovered struts in all analyzable struts
      and in the residual struts without malapposed segments among the 3 groups.
      RESULTS: Group III showed a significantly larger percentage of uncovered struts
      among all the struts (group I, 3.7 +/- 6.4 vs. II, 5.5 +/- 5.6 vs. III, 17.6 +/-
      15.9%, P < 0.001) and among residual struts without malapposed segments (3.7 +/-
      6.4 vs. 5.2 +/- 5.7 vs. 15.0 +/- 14.4%, respectively, P < 0.001). There was a
      significant correlation between malapposed and uncovered struts in group III (r =
      0.393, P = 0.016), but not in group II (r =-0.007, P = 0.965) among residual
      struts without malapposed segments. CONCLUSION: The percentage of uncovered DES
      struts was quite different depending on the presence and extent of malapposed
      struts.

PMID- 22372891
TI  - Stimulated release of cholesterol from liposomal membranes by a PEGylated
      phospholipid.
AB  - PEGylated phospholipids are commonly used to increase the blood-circulation time
      of liposomes by providing a steric barrier around them. This paper documents a
      fundamentally new property of these lipids-an ability to stimulate the release of
      cholesterol from phospholipid membranes. Evidence for such stimulation has been
      obtained by measuring the transport of dehydroergosterol (DHE), a fluorescent
      simulant of cholesterol, from donor liposomes made from 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine
      N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG(2000)), and DHE to acceptor
      liposomes made from POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol
      (POPG), and cholesterol. The potential of PEGylated lipids to serve as novel
      cholesterol-lowering agents is briefly discussed.

PMID- 22372892
TI  - Near-membrane ensemble elongation in the proline-rich LRP6 intracellular domain
      may explain the mysterious initiation of the Wnt signaling pathway.
AB  - BACKGROUND: LRP6 is a membrane protein crucial in the initiation of canonical
      Wnt/beta-catenin signalling. Its function is dependent on its proline-serine rich
      intracellular domain. LRP6 has five PPP(S/T)P motifs that are phosphorylated
      during activation, starting with the site closest to the membrane. Like all long
      proline rich regions, there is no stable 3D structure for this isolated,
      contiguous region. RESULTS: In our study, we use a computational simulation tool
      to sample the conformational space of the LRP6 intracellular domain, under the
      spatial constraints imposed by (a) the membrane and (b) the close approach of the
      neighboring intracellular molecular complex, which is assembled on Frizzled when
      Wnt binds to both LRP6 and Frizzled on the opposite side of the membrane. We
      observe that an elongated form dominates in the LRP6 intracellular domain
      structure ensemble. This elongation could relieve conformational auto-inhibition
      of the PPP(S/T)PX(S/T) motif binding sites and allow GSK3 and CK1 to approach
      their phosphorylation sites, thereby activating LRP6 and the downstream pathway.
      CONCLUSIONS: We propose a model in which the conformation of the LRP6
      intracellular domain is elongated before activation. This is based on the
      intrusion of the Frizzled complex into the ensemble space of the proline rich
      region of LRP6, which alters the shape of its available ensemble space. To test
      whether this observed ensemble conformational change is sequence dependent, we
      did a control simulation with a hypothetical sequence with 50% proline and 50%
      serine in alternating residues. We confirm that this ensemble neighbourhood-based
      conformational change is independent of sequence and conclude that it is likely
      found in all proline rich sequences. These observations help us understand the
      nature of proline rich regions which are both unstructured and which seem to
      evolve at a higher rate of mutation, while maintaining sequence composition.

PMID- 22372894
TI  - Sverdlovsk revisited: pulmonary pathology of inhalational anthrax versus
      anthraxlike Bacillus cereus pneumonia.

PMID- 22372896
TI  - Proteomics?

PMID- 22372898
TI  - When melanoma is negative for S100: diagnostic pitfalls.

PMID- 22372899
TI  - Introduction to continuing special series.

PMID- 22372900
TI  - Epithelioid lesions of the serosa.
AB  - CONTEXT: Diagnosing epithelioid serosal lesions remains a challenge because
      numerous different processes-primary or secondary, benign or malignant-occur in
      body cavities, some of which are very rare. OBJECTIVES: To review the newest
      literature and to describe the morphologic criteria and immunohistochemical
      markers that are useful for distinguishing epithelioid serosal lesions. DATA
      SOURCES: Previously published literature concentrating on the newest research
      findings. Earlier reviews are principally referred to for established diagnostic
      criteria. CONCLUSIONS: Immunohistochemistry with a panel of antibodies has made
      the diagnosis of epithelioid serosal lesions very reliable. When deciding on
      antibodies used in differential diagnosis, it is important to consider tumor
      location, clinical and radiologic information, and morphologic features.
      Immunohistochemistry is less useful in the differential diagnosis of benign
      versus malignant mesothelial lesions. The diagnosis of benign versus malignant
      mesothelial proliferations still relies on the histologic criteria of invasion.

PMID- 22372901
TI  - Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma.
AB  - CONTEXT: The pathologic approach to pleural-based lesions is stepwise and uses
      morphologic assessment, correlated with clinical and imaging data supplemented by
      immunohistochemistry (IHC), and more recently, molecular tests, as an aid for 2
      main diagnostic problems: malignant mesothelioma (MM) versus other malignant
      tumors and malignant versus reactive mesothelial proliferations. OBJECTIVE: To
      present the current knowledge regarding IHC and molecular tests with respect to
      MM diagnosis, and in particular, the differentiation of the epithelioid type of
      MM from carcinoma metastatic to the pleural cavity. DATA SOURCES: A review of
      immunohistochemical features of 286 consecutive MMs from 459 cases of pleural
      pathology, diagnosed during routine practice from 2003 to 2009. A survey of
      biomedical journal literature from MedLine/PubMed (US National Library of
      Medicine) focused on MM and associated tissue-based diagnostic IHC markers and
      molecular tests. CONCLUSIONS: The search for a single diagnostic marker of MM has
      so far been discouraging, given the biologic and phenotypic tumor heterogeneity
      of MM. The use of antibody panels has gained unanimous acceptance especially in
      the differential diagnosis between MM and metastatic carcinoma, whereas the
      usefulness of IHC is more limited when dealing with spindle cell malignancies or
      distinguishing malignant from reactive mesothelium. A great degree of
      interlaboratory variability in antibody combinations and clone selection within
      diagnostic panels still exists. Current investigations aim at selecting the most
      suitable and cost-effective combination of antibodies by using novel statistical
      approaches for assessing diagnostic performance beyond the traditional measures
      of sensitivity and specificity.

PMID- 22372902
TI  - Mesothelioma not associated with asbestos exposure.
AB  - CONTEXT: Despite asbestos being identified as the single most important cause of
      malignant mesothelioma, the tumor is known to occur in only 10% to 20% of heavily
      exposed individuals. In addition, about 20% of the patients have no history of
      asbestos exposure even after detailed assessment. Therefore, there has been
      speculation for some time that asbestos alone may not be sufficient to cause
      mesothelioma and that other factors may be involved either as cocarcinogens or as
      independent mechanisms of cancer causation. OBJECTIVE: To give a brief review of
      nonasbestos fiber erionite and therapeutic radiation as 2 established examples of
      asbestos-independent mechanisms, of the potential emerging role of man-made
      fibers such as carbon nanotubes, and of polyoma virus SV40 (simian virus 40) as a
      potential example of the cocarcinogenic mode of involvement. DATA SOURCES:
      Relevant recent literature has been surveyed to portray and provide the evidence
      in favor of the examples. CONCLUSIONS: Erionite has emerged as the most important
      example of nonasbestos-mediated cause of mesothelioma in regions such as Turkey
      where exposure to this type of fiber is highly prevalent. Recently, the polyoma
      virus SV40 has been unexpectedly discovered as an effective cocarcinogen of
      asbestos in the causation of animal mesothelioma, though despite considerable
      research, its potential role in human mesothelioma remains unproven.

PMID- 22372903
TI  - Lymphoproliferative conditions of the serosa.
AB  - CONTEXT: A diverse and complex variety of lymphoproliferative diseases may
      involve the serosa, with widely differing clinical outcomes encompassing a
      spectrum of benign and malignant conditions. OBJECTIVE: To review
      lymphoproliferative disease involving the serosa and to provide a practical
      approach to the evaluation of lymphoid and plasma cell infiltrates in the serosa,
      together with a review of various tumors and tumorlike conditions that may mimic
      lymphoproliferative disease. DATA SOURCES: Analysis of published literature.
      CONCLUSIONS: All forms of hematologic malignancy may involve the various serosal
      sites, although this is usually observed as secondary involvement in persons with
      known lymph nodal, marrow-based, or extranodal disease. Primary pericardial,
      pleural, and peritoneal lymphomas are rare; many nonneoplastic conditions may
      mimic lymphoma and a variety of nonhematolymphoid tumors may simulate hematologic
      malignancies. An understanding of the role of ancillary tests, together with an
      appreciation of their limitations, will prevent misdiagnosis.

PMID- 22372904
TI  - Molecular changes in mesothelioma with an impact on prognosis and treatment.
AB  - CONTEXT: In recent decades, research on malignant pleural mesothelioma (MPM) has
      been developed to improve patients' outcomes by increasing the level of
      confidence in MPM diagnosis and prognosis. OBJECTIVE: To summarize data on
      genetic and epigenetic abnormalities in MPM that may be of interest for a better
      management of patients with MPM. DATA SOURCES: Data were obtained from scientific
      publications on genetic and epigenetic abnormalities in MPM by studying gene
      mutations, DNA methylation, and gene and microRNA expression profiling.
      CONCLUSIONS: Molecular changes in MPM consist in altered expression and in
      activation or inactivation of critical genes in oncogenesis, especially tumor
      suppressor genes at the INK4 and NF2 loci. Activation of membrane receptor
      tyrosine kinases and deregulation of signaling pathways related to
      differentiation, survival, proliferation, apoptosis, cell cycle control,
      metabolism, migration, and invasion have been demonstrated. Alterations that
      could be targeted at a global level (methylation) have been recently reported.
      Experimental research has succeeded especially in abolishing proliferation and
      triggering apoptosis in MPM cells. So far, targeted clinical approaches focusing
      on receptor tyrosine kinases have had limited success. Molecular analyses of
      series of MPM cases have shown that defined alterations are present in MPM
      subsets, consistent with interindividual variations of molecular alterations, and
      suggesting that identification of patient subgroups will be essential to develop
      more specific therapies.

PMID- 22372905
TI  - Pretransfusion testing practices in North America, 2005-2010: an analysis of the
      College Of American Pathologists Interlaboratory Comparison Program J-survey
      data, 2005-2010.
AB  - CONTEXT: Data collection and analysis of the College of American Pathologists
      (CAP) Interlaboratory Comparison Program (Proficiency Testing) J-Survey results
      provide insights into North American pretransfusion compatibility testing
      practices and trends. OBJECTIVES: To assess current North American manual testing
      practices for ABO grouping, rhesus (Rh) typing, antibody screening, and
      crossmatching using CAP proficiency testing data. DESIGN: Analysis of the CAP
      Interlaboratory Comparison Program J-Survey data (2005-2010) to identify
      laboratory methods used for ABO grouping, Rh typing, antibody screening, and
      crossmatching. Data were analyzed by test method using Microsoft (Redmond,
      Washington) Excel software. RESULTS: The method used most often in ABO grouping
      and Rh typing was tube testing. Many laboratories also used tube testing for
      antibody detection and crossmatching, but during the study period, the proportion
      of laboratories using gel-based methodologies increased considerably.
      CONCLUSIONS: Most North American CAP laboratories continue to use tube methods
      for ABO/Rh testing. Use of gel-based methodologies increased during the past 5
      years for antibody screening and crossmatching.

PMID- 22372906
TI  - Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the
      diagnosis of acquired immunodeficiency syndrome-related and non-acquired
      immunodeficiency syndrome-related Kaposi sarcoma.
AB  - CONTEXT: Kaposi sarcoma (KS) is a vascular tumor frequently associated with
      advanced human immunodeficiency virus infection, advanced age, or iatrogenic
      immunosuppression. Immunohistochemistry for CD31 and CD34, and more recently for
      FLI1 and D2-40, has been used as ancillary diagnostic tests for KS, despite
      little information regarding the sensitivities and differential staining patterns
      of the latter 2 markers in the major clinical subtypes and histologic stages of
      KS. OBJECTIVE: This retrospective study aims to assess the prevalence of the
      vascular markers D2-40 and FLI1 in the main clinical subgroups and tumor stages
      of KS. DESIGN: Twenty-four cases of KS (12 acquired immunodeficiency syndrome
      [AIDS]-related cases and 12 non-AIDS-related cases; 11 nodular-stage and 13
      patch/plaque-stage KS) were stained for CD34, CD31, D2-40, and FLI1 by
      immunohistochemistry. The distribution of immunoreactivity was compared between
      the clinical subtypes and tumor stages of KS using the Mann-Whitney test.
      RESULTS: CD31, CD34, D2-40, and FLI1 strongly and diffusely stained tumor cells
      in 75%, 92%, 67%, and 92% of AIDS-related cases and 58%, 92%, 67%, and 75% of non
      AIDS-related cases, respectively. Differences in the proportions of positive
      cases between AIDS-related and non-AIDS-related cases did not reach statistical
      significance. No significant staining differences were observed between nodular-
      and patch/plaque-stage KS either. CONCLUSIONS: There are no differences in the
      distribution of immunohistochemical reactivity for CD31, CD34, D2-40, or FLI1
      between AIDS-related and non-AIDS-related KS or between nodular- and patch/plaque
      stage KS. All of the markers studied demonstrated high sensitivity in both
      clinical settings and both stages of tumor progression.

PMID- 22372907
TI  - Human immunodeficiency virus-related gastrointestinal pathology: a southern
      Africa perspective with review of the literature (part 1: infections).
AB  - CONTEXT: Human immunodeficiency virus infection is rife in sub-Saharan Africa and
      in southern Africa in particular. Despite the increasing availability of
      antiretroviral therapy in this region, opportunistic infections remain common and
      frequently involve the gastrointestinal tract. OBJECTIVE: To review the
      histopathologic findings and distinguishing features of human immunodeficiency
      virus-associated gastrointestinal infections in southern Africa and relate those
      findings to the documented international literature. DATA SOURCES: The available
      literature on this topic was reviewed and supplemented with personal experience
      in a private histopathology practice in South Africa. CONCLUSIONS: In southern
      Africa, the range of gastrointestinal, opportunistic infectious pathology in
      human immunodeficiency virus afflicted patients is diverse and includes viral,
      bacterial, fungal, and parasitic infections. This infectious pathology is
      sometimes a manifestation of systemic disease. In profoundly immunocompromised
      patients, unusual histologic features, involvement of uncommon gastrointestinal
      tract sites, and more than one pathogen may be seen.

PMID- 22372908
TI  - Human immunodeficiency virus-related gastrointestinal pathology: a southern
      Africa perspective with review of the literature (part 2: neoplasms and
      noninfectious disorders).
AB  - CONTEXT: Human immunodeficiency virus (HIV) infection is rife in sub-Saharan
      Africa and in southern Africa in particular. Despite the increasing availability
      of antiretroviral therapy in this region, HIV-associated neoplasms remain common
      and frequently involve the gastrointestinal tract, which may also demonstrate
      other noninfectious, HIV-related pathology. OBJECTIVE: To review the
      histopathologic findings and distinguishing features of neoplastic and
      noninfectious, HIV-associated gastrointestinal disorders in southern Africa and
      relate those findings to the documented international literature. DATA SOURCES:
      The available literature on this topic was reviewed and supplemented with
      personal experience in a private histopathology practice in South Africa.
      CONCLUSIONS: In southern Africa, a diverse range of HIV-related neoplasms and
      noninfectious gastrointestinal disorders is seen, but published data for the
      region are scarce. The gastrointestinal disorders include drug-associated
      pathology, gastrointestinal manifestations of the immune reconstitution
      inflammatory syndrome, idiopathic chronic esophageal ulceration, and the
      controversial entity of HIV enteropathy.

PMID- 22372909
TI  - Signet-ring cell melanoma of the gastroesophageal junction: a case report and
      literature review.
AB  - We report the first case, to our knowledge, of a possible primary, signet-ring
      cell melanoma of the gastroesophageal junction. The mass was initially diagnosed
      as an invasive, poorly differentiated carcinoma; however, on further review and
      immunohistochemical workup, the diagnosis of signet-ring cell melanoma was made.
      The lesion consisted of oval to round epithelioid cells undermining the gastric
      mucosa and infiltrating the muscularis mucosae. Tumor cells demonstrated abundant
      cytoplasm and eccentrically located nuclei, many with signet-ring cell
      morphology. The tumor cells were negative for mucin and pancytokeratin, strongly
      positive for S100 protein and Melan-A, and focally but strongly positive for
      human melanoma black-45. Diagnostic imaging failed to prove another site of
      melanoma, and no history of melanoma or cutaneous lesion was reported by the
      patient. Therefore, it was determined this was likely a primary lesion. We review
      the literature and previously reported cases of this rare histologic variant of
      melanoma.

PMID- 22372910
TI  - Metastatic Crohn disease: a rare cutaneous entity.
AB  - Metastatic Crohn disease is a rare cutaneous disorder characterized by
      noncaseating, granulomatous skin lesions present at sites anatomically separate
      from the gastrointestinal tract. It is the least common dermatologic
      manifestation of Crohn disease, and the differential diagnosis includes numerous
      similarly appearing, granulomatous skin entities. Males and females appear to be
      equally affected, and children tend to present with clinical lesions different
      from those of adults. An integration of clinical information, microscopic
      findings, and ancillary studies is necessary to accurately diagnose this rare
      cutaneous disease. Our objective is to review the clinical features,
      histopathologic characteristics, suggested pathogenesis, differential diagnosis,
      and current therapeutic options of metastatic Crohn disease.

PMID- 22372911
TI  - Intravascular large B-cell lymphoma.
AB  - A rare type of diffuse large B-cell lymphoma, intravascular large B-cell lymphoma
      primarily affects the middle-aged to elderly population, with a slight
      predominance in men. By the time of presentation, most patients have advanced,
      disseminated disease, and often the diagnosis is made at autopsy. Patients may
      present with any of a myriad of symptoms, with any tissue potentially being
      infiltrated. Central nervous system and cutaneous involvement is common, as is
      the presence of B symptoms including fever, weight loss, and night sweats.
      Morphologically, growth of neoplastic cells is restricted to the lumen of small
      vessels. The cells are large, with 1 or more prominent nucleoli, scant cytoplasm,
      and frequent mitotic figures, and are commonly positive for cluster of
      differentiation markers 79a, 20, and 19, as well as MUM1/IRF4 and Bcl-2.
      Intravascular large B-cell lymphoma is aggressive, and without treatment is
      rapidly fatal.

PMID- 22372912
TI  - DevR (DosR) binding peptide inhibits adaptation of Mycobacterium tuberculosis
      under hypoxia.
AB  - DevR is a key regulator of the dormancy response in Mycobacterium tuberculosis
      (M. tb). Using DevR as bait to screen a phage display library, a peptide, DevRS1,
      was obtained. DevRS1 inhibited DevR-regulated transcription and survival of
      nonreplicating tubercle bacilli in a hypoxia model of dormancy. DevRS1 peptide
      mediated inhibition demonstrates the efficacy of intercepting DevR function to
      block hypoxic adaptation of M. tb.

PMID- 22372914
TI  - Relation between the charge efficiency of activated carbon fiber and its
      desalination performance.
AB  - Four types of activated carbon fibers (ACFs) with different specific surface
      areas (SSA) were used as electrode materials for water desalination using
      capacitive deionization (CDI). The carbon fibers were characterized by scanning
      electron microscopy and N(2) adsorption at 77 K, and the CDI process was
      investigated by studying the salt adsorption, charge transfer, and also the
      charge efficiency of the electric double layers that are formed within the
      micropores inside the carbon electrodes. It is found that the physical adsorption
      capacity of NaCl by the ACFs increases with increasing Brunauer-Emmett-Teller
      (BET) surface area of the fibers. However, the two ACF materials with the highest
      BET surface area have the lowest electrosorptive capability. Experiments indicate
      that the charge efficiency of the double layers is a key property of the ACF
      based electrodes because the ACF material which has the maximum charge efficiency
      also shows the highest salt adsorption capacity for CDI.

PMID- 22372913
TI  - Influence of crown ferrule heights and dowel material selection on the mechanical
      behavior of root-filled teeth: a finite element analysis.
AB  - PURPOSE: This study used the 3D finite element (FE) method to evaluate the
      mechanical behavior of a maxillary central incisor with three types of dowels
      with variable heights of the remaining crown structure, namely 0, 1, and 2 mm.
      MATERIALS AND METHODS: Based on computed microtomography, nine models of a
      maxillary central incisor restored with complete ceramic crowns were obtained,
      with three ferrule heights (0, 1, and 2 mm) and three types of dowels (glass
      fiber = GFD; nickel-chromium = NiCr; gold alloy = Au), as follows: GFD0--restored
      with GFD with absence (0 mm) of ferrule; GFD1--similar, with 1 mm ferrule; GFD2-
      glass fiber with 2 mm ferrule; NiCr0--restored with NiCr alloy dowel with absence
      (0 mm) of ferrule; NiCr1--similar, with 1 mm ferrule; NiCr2--similar, with 2 mm
      ferrule; Au0--restored with Au alloy dowel with absence (0 mm) of ferrule; Au1-
      similar, with 1 mm ferrule; Au2--similar, with 2 mm ferrule. A 180 N distributed
      load was applied to the lingual aspect of the tooth, at 45 degrees  to the tooth
      long axis. The surface of the periodontal ligament was fixed in the three axes (x
      = y = z = 0). The maximum principal stress (sigma(max)), minimum principal stress
      (sigma(min)), equivalent von Mises (sigma(vM)) stress, and shear stress
      (sigma(shear)) were calculated for the remaining crown dentin, root dentin, and
      dowels using the FE software. RESULTS: The sigma(max) (MPa) in the crown dentin
      were: GFD0 = 117; NiCr0 = 30; Au0 = 64; GFD1 = 113; NiCr1 = 102; Au1 = 84; GFD2 =
      102; NiCr2 = 260; Au2 = 266. The sigma(max) (MPa) in the root dentin were: GFD0 =
      159; NiCr0 = 151; Au0 = 158; GFD1 = 92; NiCr1 = 60; Au1 = 67; GFD2 = 97; NiCr2 =
      87; Au2 = 109. CONCLUSION: The maximum stress was found for the NiCr dowel,
      followed by the Au dowel and GFD; teeth without ferrule are more susceptible to
      the occurrence of fractures in the apical root third.

PMID- 22372915
TI  - Flexible ureterorenoscopy versus extracorporeal shock wave lithotripsy for
      treatment of lower pole stones of 10-20 mm.
AB  - What's known on the subject? and What does the study add? Shock wave lithotripsy
      and flexible ureterorenoscopy are acceptable treatment options for lower pole
      stones smaller than 10 mm, while percutaneous nephrolithotomy is the favoured
      treatment for stones larger than 20 mm. For treatment of lower pole stones of 10
      20 mm, flexible ureterorenoscopy has a significantly higher stone-free rate and
      lower retreatment rate than shock wave lithotripsy. OBJECTIVE: To compare the
      outcomes of flexible ureterorenoscopy (F-URS) and extracorporeal shock wave
      lithotripsy (ESWL) for treatment of lower pole stones of 10-20 mm. PATIENTS AND
      METHODS: The database of patients with a single lower pole stone of 10-20 mm was
      examined to obtain two matched groups who were treated with F-URS or ESWL.
      Matching criteria were stone length, side and patient gender. Stone-free rates
      were evaluated 3 months after the last treatment session by non-contrast computed
      tomography. Both groups were compared for retreatment rate, complications and
      stone-free rate. RESULTS: The matched groups included 37 patients who underwent F
      URS and 62 patients who underwent ESWL. Retreatment rate was significantly higher
      for ESWL (60% vs 8%, P < 0.001). Complications were more after F-URS (13.5% vs
      4.8%), but the difference was not significant (P= 0.146). All complications were
      grade II or IIIa on modified Clavien classification. The stone-free rate was
      significantly better after F-URS (86.5% vs 67.7%, P= 0.038). One failure of F-URS
      (2.7%) and five failures (8%) of ESWL were treated with percutaneous
      nephrolithotomy. Significant residual fragments in three patients (8%) after F
      URS were treated with ESWL, while significant residual fragments after ESWL in
      five patients (8%) were treated with F-URS. Residual fragments (<4 mm) were
      followed every 3 months in one patient (2.7%) after F-URS and in 10 patients
      (16%) after ESWL. CONCLUSIONS: For treatment of lower pole stones of 10-20 mm, F
      URS provided significantly higher stone-free rate and lower retreatment rate
      compared with ESWL. The incidence of complications after F-URS was not
      significantly more than after ESWL.

PMID- 22372916
TI  - Role of excipients in successful development of self-emulsifying/microemulsifying
      drug delivery system (SEDDS/SMEDDS).
AB  - The oral delivery of hydrophobic drug presents a major challenge because of the
      low aqueous solubility of such compounds. Self-emulsifying/microemulsifying drug
      delivery system (SEDDS/SMEDDS), which are isotropic mixtures of oils,
      surfactants, solvents and co-solvents/surfactants, can be used for the design of
      formulations in order to improve the oral absorption of highly lipophilic drug
      compounds. The efficiency of oral absorption of said drug from such type of
      formulation depends on many formulation-related parameters, such as surfactant
      concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and
      charge, all of which in essence determine the self-emulsification ability. Thus,
      only very specific pharmaceutical excipient combinations will lead to efficient
      self-emulsifying systems. With the growing interest in this field, there is an
      increasing need for guidelines in excipient selection to obtain effective
      delivery system with improved bioavailability.   The aim of this review is to
      present the recent approaches in selecting the most appropriate lipid system(s);
      methods for its characterization and role of various excipients for improved
      delivery of dosage form.

PMID- 22372917
TI  - Brevisulcenal-F: a polycyclic ether toxin associated with massive fish-kills in
      New Zealand.
AB  - A novel marine toxin, brevisulcenal-F (KBT-F, from karenia brevisulcata toxin)
      was isolated from the dinoflagellate Karenia brevisulcata. A red tide of K.
      brevisulcata in Wellington Harbour, New Zealand, in 1998 was extremely toxic to
      fish and marine invertebrates and also caused respiratory distress in harbor
      bystanders. An extract of K. brevisulcata showed potent mouse lethality and
      cytotoxicity, and laboratory cultures of K. brevisulcata produced a range of
      novel lipid-soluble toxins. A lipid soluble toxin, KBT-F, was isolated from bulk
      cultures by using various column chromatographies. Chemical investigations showed
      that KBT-F has the molecular formula C(107)H(160)O(38) and a complex polycyclic
      ether nature. NMR and MS/MS analyses revealed the complete structure for KBT-F,
      which is characterized by a ladder-frame polyether scaffold, a 2-methylbut-2-enal
      terminus, and an unusual substituted dihydrofuran at the other terminus. The main
      section of the molecule has 17 contiguous 6- and 7-membered ether rings. The
      LD(50) (mouse i.p.) for KBT-F was 0.032 mg/kg.

PMID- 22372918
TI  - Infant health effects of a nurse-community health worker home visitation
      programme: a randomized controlled trial.
AB  - BACKGROUND:   Home visiting is supported as a way to improve child health and
      development. Home visiting has been usually provided by nurses or community
      health workers (CHWs). Few studies compared the child health advantages of a
      nurse-CHW team approach over nurse prenatal and postnatal home visiting. METHODS:
      A randomized trial was conducted with Medicaid-insured pregnant women in Kent
      County, Michigan. Pregnant women were assigned to a team intervention including
      nurse-CHW home visitation, or standard community care (CC) including nurse home
      visitation. Morbidity was assessed in 530 infants over their first 12 months of
      life from medical claims and reported by the mother. RESULTS:   There were no
      differences in overall child health between the nurse-CHW intervention and the CC
      arm over the first year of life. There were fewer mother-reported
      asthma/wheezing/croup diagnostics in the team intervention group among infants
      whose mothers have low psychosocial resources (13% vs. 27%, P = 0.01; adjusted OR
      = 0.4, P = 0.01). There were no differences in diagnosed asthma/wheezing/croup
      documented by medical claims. There were no differences in immunizations,
      hospitalizations and ear infections. CONCLUSIONS:   There was no strong evidence
      that infant health was improved by the addition of CHWs to a programme of CC that
      included nurse home visitation. Targeting such interventions at common health
      problems of infancy and childhood or at diagnosed chronic conditions may prove
      more successful.

PMID- 22372919
TI  - Heat inactivation of Salmonella spp. in fresh poultry compost by simulating early
      phase of composting process.
AB  - AIMS: The purpose of this study was to determine the effect of moisture on
      thermal inactivation of Salmonella spp. in poultry litter under optimal
      composting conditions. METHODS AND RESULTS: Thermal inactivation of Salmonella
      was studied in fresh poultry compost by simulating early phase of composting
      process. A mixture of three Salmonella serotypes grown in Tryptic soy broth with
      rifampin (TSB-R) was inoculated in fresh compost with 40 or 50% moisture at a
      final concentration of c. 7 log CFU g(-1). The inoculated compost was kept in an
      environmental chamber which was programmed to rise from room temperature to
      target composting temperatures in 2 days. In poultry compost with optimal
      moisture content (50%), Salmonella spp. survived for 96, 72 and 24 h at 50, 55
      and 60 degrees C, respectively, as compared with 264, 144 and 72 h at 50, 55 and
      60 degrees C, respectively, in compost with suboptimal moisture (40%). Pathogen
      decline was faster during the come-up time owing to higher ammonia
      volatilization. CONCLUSIONS: Our results demonstrated that Salmonella spp.
      survived longer in fresh poultry compost with suboptimal moisture of 40% than in
      compost with optimal moisture of 50% during thermophilic composting. High
      nitrogen content of the poultry compost is an additional factor contributing to
      Salmonella inactivation through ammonia volatilization during thermal exposure.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This research validated the effectiveness
      of the current composting guidelines on Salmonella inactivation in fresh poultry
      compost. Both initial moisture level and ammonia volatilization are important
      factors affecting microbiological safety and quality of compost product.

PMID- 22372920
TI  - Treatment with unfunded drugs in oncology: the impact of access programmes and
      clinical trials.
AB  - BACKGROUND: Where proven cancer therapies remain unfunded, patients are faced
      with difficult decisions regarding personally covering some or all of the
      treatment cost. Clinical trials provide an alternative form of access to unfunded
      drugs. AIMS: To examine the patient population and utilisation of the colorectal
      cancer cetuximab Interim Access Programme (IAP) in Australia. METHODS: We
      retrospectively analysed de-identified data collected as part of the costsharing
      colorectal cancer cetuximab IAP in Australia, which extended from June 2005 until
      November 2009. The impact of the CO20 clinical trial that opened in early 2008
      and provided free access to cetuximab was also examined. RESULTS: Eight hundred
      and fifty-eight patients received >=1 treatment on the IAP. The median age of
      participants was lower than the general colorectal cancer population (61 vs 71
      years). A greater uptake by males was limited to patients over 65 years old.
      Socioeconomic status correlated with programme enrolment, and there appeared to
      be lower uptake among regional patients. The majority (93%) of patients received
      combination treatment with irinotecan, with a trend towards increasing use of
      single-agent cetuximab over time. The median time-on-treatment was longer in
      patients treated with combination therapy than with monotherapy (12 vs 8 weeks).
      The CO20 trial had minimal impact on IAP enrolment and approximately doubled the
      number of Australian patients receiving cetuximab. CONCLUSIONS: Patients' age and
      gender in older patients impacted on participation in the IAP. Both the IAP and
      the CO20 trial contributed to a substantial proportion of Australian patients
      accessing an unfunded treatment, with an estimated 50% of the eligible patient
      population receiving cetuximab.

PMID- 22372921
TI  - FOXP3 is not mutated in human melanoma.

PMID- 22372922
TI  - The genomic and proteomic blueprint of mouse megakaryocytes derived from
      embryonic stem cells.
AB  - BACKGROUND: Platelets are specialized cells, produced by megakaryocytes (MKs) in
      the bone marrow, which represent the first defense against hemorrhage. There are
      many diseases where platelet production or function is impaired, with severe
      consequences for patients. Therefore, new insights into the process of MK
      differentiation and platelet formation would have a major impact on both basic
      and clinical research. OBJECTIVES: Embryonic stem (ES) cells represent a good in
      vitro model to study the differentiation of MKs, with the possibility of being
      genetically engineered and constituting an unlimited source of MKs. However, lack
      of knowledge about the molecular identity of ES-derived MKs (ES-MKs) may prevent
      any further development and application of this model. METHODS: This paper
      presents the first comprehensive transcriptional and proteome profile analyses of
      mouse ES-MKs in comparison with MKs derived from mouse fetal liver progenitors
      (FL-MKs). RESULTS: In ES-MKs we found a down-regulation of cytoskeleton proteins,
      specific transcription factors and membrane receptors at both transcriptional and
      protein levels. At the phenotypic level, this molecular blueprint was displayed
      by ES-MKs' lower polyploidy, lower nuclear/cytoplasm ratio and reduced capacity
      to form proplatelets and releasing platelets. CONCLUSIONS: Overall our data
      demonstrate that ES-MKs represent a useful model to clarify many aspects of both
      MK physiology and pathological conditions where impaired MK functions are related
      to defective MK development, as in inherited thrombocytopenias and primary
      myelofibrosis.

PMID- 22372923
TI  - Hair as a specimen to document tetramethylene disulfotetramine exposure.
AB  - Tetramethylene disulfotetramine (tetramine) is a rodenticide that has been banned
      for many years in China. Since 2005, inhabitants of a village in the Henan
      Province have been suffering from grand mal seizures. To investigate the
      possibility of tetramine as the cause, we developed a method to determine
      tetramine in human hair. Sample preparation involved external decontamination,
      frozen pulverization, and ultrasonication in 2 mL ethyl acetate in the presence
      of cocaine-d3 as an internal standard. The method exhibited good linearity;
      calibration curve was linear over a range of 0.1-20 ng/mg hair. The limit of
      detection for the assay was 0.05 ng/mg hair. Except for one subject (No. 4), all
      head and pubic hair samples were positive for tetramine. The concentrations of
      tetramine in pubic hair were significantly higher than those in the same
      subjects' head hair samples. Because of a long retention in body, segmental head
      hair analysis cannot provide an accurate exposure history of tetramine in the
      body.

PMID- 22372924
TI  - Clinical predictors for failure of percutaneous coronary intervention in ST
      elevation myocardial infarction.
AB  - BACKGROUND: Failed percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction (STEMI) is associated with adverse outcome. With recent
      improvements in PCI techniques, the incidence and predictors for failed primary
      PCI are unclear. METHODS: A clinical database of consecutive patients who
      underwent primary or rescue PCI from 1993 to 2011 was used to compare patients
      with successful versus failed PCI. Clinical follow-up was obtained in-hospital,
      at 30 days and at 1 year. RESULTS: Of 2900 patients fulfilling our inclusion
      criteria, 111 (3.98%) had failed PCI. Patients who had failed PCI were older (65
      vs. 61 years), were more likely to be women (46% vs. 32%), were more likely to
      have previous peripheral vascular disease (19% vs. 11%), previous PCI (29% vs.
      20%), and were more likely to present with cardiogenic shock (25% vs. 11%) (all P
      < 0.05). Multivariable logistic regression analysis identified female gender (OR
      1.54; 95% CI 1.01-2.38), cardiogenic shock (2.07; 1.22-3.49), previous PCI (1.71;
      1.08-2.70), and type C lesion (2.47; 1.60-3.82) as independent predictors of PCI
      failure. The in-hospital (18% vs. 4%) and long-term mortality (48% vs. 14%) were
      worse in the failed PCI group compared to the successful group (P < 0.05).
      CONCLUSION: In patients with STEMI, primary PCI failure is uncommon. It is
      associated with worse short- and long-term clinical outcome compared with a
      successful procedure. Special care should be taken when PCI is performed in women
      at higher risk for failure when presenting with STEMI.

PMID- 22372926
TI  - Activation of Elk-1 participates as a neuroprotective compensatory mechanism in
      models of Huntington's disease.
AB  - The transcription factor Elk-1 has been revealed as neuroprotective against toxic
      stimuli. In this study, we explored the neuroprotective capacity of Elk-1 in
      Huntington's disease. To this aim, we used two exon-1 mutant huntingtin (mhtt)
      mouse models (R6/1 and R6/2), and a full-length mhtt striatal cell model
      (STHdh(Q111/Q111) ). Analysis of Elk-1 and pElk-1(Ser383) in the striatum of R6
      mice revealed increased levels during the disease progression. Similarly, Elk-1
      and pElk-1(Ser383) levels were increased in STHdh(Q111/Q111) cells when compared
      with wild-type cells. In addition, we observed a predominant nuclear localization
      of Elk-1 in STHdh(Q111/Q111) cells, and in the striatum of 30-week-old R6/1 mice.
      Nuclear Elk-1 did not colocalize with mhtt aggregates, suggesting a higher
      transcriptional activity. In agreement, the knock-down of Elk-1 decreased
      immediate early genes expression in STHdh(Q111/Q111) cells, but not in wild-type
      cells. Interestingly, reduction of Elk-1 levels by siRNAs transfection promoted
      cell death and caspase 3 cleavage in STHdh(Q111/Q111) cells, but not in wild-type
      cells. In summary, we propose that increased protein levels, phosphorylation and
      nuclear localization of Elk-1 observed in exon-1 and full-length Huntington's
      disease models could be a compensatory mechanism activated by striatal cells in
      response to the presence of mhtt that contributes to neuroprotection.

PMID- 22372927
TI  - A new approach for pyrazinamide susceptibility testing in Mycobacterium
      tuberculosis.
AB  - BACKGROUND: Pyrazinamide (PZA) is an important drug in the treatment of
      tuberculosis. Microbiological methods of PZA susceptibility testing are
      controversial and have low reproducibility. After conversion of PZA into
      pyrazinoic acid (POA) by the bacterial pyrazinamidase enzyme, the drug is
      expelled from the bacteria by an efflux pump. OBJECTIVE: To evaluate the rate of
      POA extrusion from Mycobacterium tuberculosis as a parameter to detect PZA
      resistance. METHODS: The rate of POA extrusion and PZA susceptibility determined
      by BACTEC 460 were measured for 34 strains in a previous study. PZA resistance
      was modeled in a logistic regression with the pyrazinoic efflux rate. RESULT: POA
      efflux rate predicted PZA resistance with 70.83%-92.85% sensitivity and 100%
      specificity compared with BACTEC 460. CONCLUSION: POA efflux rate could be a
      useful tool for predicting PZA resistance in M. tuberculosis. Further exploration
      of this approach may lead to the development of new tools for diagnosing PZA
      resistance, which may be of public health importance.

PMID- 22372929
TI  - Immunoisolation of islets in high guluronic acid barium-alginate microcapsules
      does not improve graft outcome at the subcutaneous site.
AB  - The survival and function of alginate microencapsulated islets is suboptimal when
      transplanted to the intraperitoneal site of diabetic animals. The large capacity
      and convenience of the subcutaneous site make it an appropriate and attractive
      alternative for microencapsulated grafts. Nonencapsulated and high guluronic acid
      barium-alginate microencapsulated islets were transplanted to the intraperitoneal
      and subcutaneous sites of diabetic mice. Microencapsulation improved graft
      success up to 28 days at the intraperitoneal site but not at the subcutaneous
      site. Samples of microencapsulated islets transplanted into normoglycemic mice
      confirmed that insulin secretion, insulin content, and adenosine triphosphate
      content were reduced more significantly in subcutaneous graft islets than
      intraperitoneal graft islets after 7 days. In addition, a greater proportion of
      dead cells were observed in the subcutaneous graft islets than in intraperitoneal
      graft islets after 28 days. We conclude that using alginate microencapsulated
      islets transplanted to the unmodified subcutaneous site is insufficient to
      reverse the diabetic state. This finding is likely to be related to the inability
      of the site to support islet function and viability.

PMID- 22372930
TI  - Construction of recombinant Newcastle disease virus Italien strain for oncolytic
      virotherapy of tumors.
AB  - Newcastle disease virus (NDV) is a naturally oncolytic virus that has been shown
      to be safe and effective for cancer therapy. Tumor virotherapy using NDV emerged
      in the 1950s and has advanced more recently by the increased availability of
      reverse genetics technology. In this study, we constructed a reverse genetics
      system based on the virulent and oncolytic NDV Italien strain, and generated two
      recombinant NDVs carrying a gene encoding either enhanced green fluorescent
      protein or firefly luciferase. We evaluated the replication and antitumor
      characteristics of these viruses in vitro and in vivo. Our data showed that the
      insertion of exogenous reporter genes did not affect NDV replication and
      sensitivity to type I interferon. The recombinant NDVs kept the property of tumor
      selective replication both in vitro and in vivo and strongly induced syncytium
      formation leading to cell death. Moreover, the recombinant NDVs significantly
      prolonged the survival of tumor-bearing athymic mice (p=0.017) and suppressed the
      loss of body weight after intratumoral injection. Taken together, our study
      provides a novel platform to develop recombinant oncolytic viruses based on the
      NDV Italien strain and shows the efficiency of recombinant NDV Italien for
      oncolytic virotherapy of tumors.

PMID- 22372931
TI  - Carbazole alkaloids from the stems of Clausena lansium.
AB  - Ten new carbazole alkaloids, claulansines A-J (1-10), and seven known analogues
      (11-17) were isolated from the stems of Clausena lansium. Their structures were
      established on the basis of extensive spectroscopic analyses, and their absolute
      configurations were determined by CD experiments and computational methods.
      Screening results indicated that compounds 1, 6, 8-10, 13, 14, and 17 showed
      selective neuroprotective effects at the concentration of 10 MUM.

PMID- 22372932
TI  - Central administration of aminoprocalcitonin inhibits food intake and stimulates
      the hypothalamic-pituitary-adrenal axis in rats via the corticotrophin-releasing
      factor system.
AB  - Aminoprocalcitonin (N-PCT), a neuroendocrine peptide derived from procalcitonin,
      reduces food intake and body weight when administered centrally in rats. We have
      recently shown that N-PCT is expressed in brain areas known to be involved in
      energy homeostasis, including the paraventricular nucleus (PVN) of the
      hypothalamus, which contains a prominent population of corticotrophin-releasing
      factor (CRF)-synthesising neurones. CRF plays a pivotal role in the regulation of
      the hypothalamic-pituitary adrenal (HPA) axis and food intake. However, little is
      known about functional interactions of N-PCT and CRF. In the present study, we
      found endogenous N-PCT protein in the rat PVN. We also showed N-PCT
      immunoreactivity in PVN co-localised with NeuN, a neuronal marker, or glial
      fibrillary acidic protein, an astrocyte marker. Double staining
      immunohistochemistry revealed that N-PCT co-localised with CRF in parvocellular
      neurones of the PVN. Intracerebroventricular N-PCT administration increased CRF
      mRNA and content in the hypothalamus, suggesting that N-PCT stimulates the HPA
      axis and suppresses food intake and body weight via CRF-dependent pathways. In
      keeping with this, i.c.v. co-injection of D-Phe-CRF(12-41), a CRF receptor
      antagonist, significantly attenuated N-PCT-induced reduction in food intake and
      body weight in a dose-dependent manner. Furthermore, i.c.v. administration of N
      PCT increased plasma adrenocorticotrophic hormone and corticosterone
      concentrations and induced the expression of Fos protein, a marker of neuronal
      activity, in parvocellular CRF neurones. These data collectively support the
      hypothesis that N-PCT inhibits food intake and body weight and stimulates the HPA
      axis via CRF-mediated pathways.

PMID- 22372933
TI  - End-point immobilization of recombinant thrombomodulin via sortase-mediated
      ligation.
AB  - We report an enzymatic end-point modification and immobilization of recombinant
      human thrombomodulin (TM), a cofactor for activation of anticoagulant protein C
      pathway via thrombin. First, a truncated TM mutant consisting of epidermal growth
      factor-like domains 4-6 (TM(456)) with a conserved pentapeptide LPETG motif at
      its C-terminal was expressed and purified in E. coli. Next, the truncated TM(456)
      derivative was site-specifically modified with N-terminal diglycine containing
      molecules such as biotin and the fluorescent probe dansyl via sortase A (SrtA)
      mediated ligation (SML). The successful ligations were confirmed by SDS-PAGE and
      fluorescence imaging. Finally, the truncated TM(456) was immobilized onto an N
      terminal diglycine-functionalized glass slide surface via SML directly.
      Alternatively, the truncated TM(456) was biotinylated via SML and then
      immobilized onto a streptavidin-functionalized glass slide surface indirectly.
      The successful immobilizations were confirmed by fluorescence imaging. The
      bioactivity of the immobilized truncated TM(456) was further confirmed by protein
      C activation assay, in which enhanced activation of protein C by immobilized
      recombinant TM was observed. The sortase A-catalyzed surface ligation took place
      under mild conditions and occurs rapidly in a single step without prior chemical
      modification of the target protein. This site-specific covalent modification
      leads to molecules being arranged in a definitively ordered fashion and
      facilitating the preservation of the protein's biological activity.

PMID- 22372934
TI  - Distribution and decline of human pathogenic bacteria in soil after application
      in irrigation water and the potential for soil-splash-mediated dispersal onto
      fresh produce.
AB  - AIMS: To improve our understanding of the survival and splash-mediated transfer
      of zoonotic agents and faecal indicator bacteria introduced into soils used for
      crop cultivation via contaminated irrigation waters. METHODS AND RESULTS:
      Zoonotic agents and an Escherichia coli marker bacterium were inoculated into
      borehole water, which was applied to two different soil types in early-, mid- and
      late summer. Decline of the zoonotic agents was influenced by soil type. Marker
      bacteria applied to columns of two soil types in irrigation water did not
      concentrate at the surface of the soils. Decline of zoonotic agents at the
      surface was influenced by soil type and environmental conditions. Typically,
      declines were rapid and bacteria were not detectable after 5 weeks. Selective
      agar strips were used to determine that the impact of water drops 24-87 MUl could
      splash marker bacteria from soil surfaces horizontal distances of at least 25 cm
      and heights of 20 cm. CONCLUSIONS: Soil splash created by rain-sized water
      droplets can transfer enteric bacteria from soil to ready-to-eat crops.
      Persistence of zoonotic agents was reduced at the hottest part of the growing
      season when irrigation is most likely. SIGNIFICANCE AND IMPACT OF THE STUDY: Soil
      splash can cause crop contamination. We report the penetration depths and
      seasonally influenced declines of bacteria applied in irrigation water into two
      soil types.

PMID- 22372935
TI  - Bilateral implant-retained auricular prosthesis for a patient with congenitally
      missing ears. A clinical report.
AB  - Microtia is a major congenital anomaly of the external ear. It includes a
      spectrum of deformities from a grossly normal but small ear to the absence of the
      entire external ear. These deformities account for three in every 10,000 births,
      with bilaterally missing ears seen in fewer than 10% of all cases. Congenital
      abnormalities of the ear are unlikely to result in the complete absence of the
      ears, but the patient presented in this article had bilateral congenitally
      missing ears. There was loss of anatomic landmarks and alteration of normal bony
      architecture. Minimal tissue was available for retention; therefore, conventional
      techniques could not be used for achieving retention. A two-implant-supported
      auricular prosthesis was planned, but the patient was found to have deficient
      bone in the implant site. Hence the implants were placed posterior to these
      sites, and the superstructure was modified to accommodate for this change in
      position of the implant to ensure the esthetic positioning of the prosthesis.

PMID- 22372936
TI  - Access to anticancer drugs: many evidence-based treatments are off-label and
      unfunded by the Pharmaceutical Benefits Scheme.
AB  - BACKGROUND: The off-label use of a drug refers to a use outside the terms of its
      approval by the Therapeutic Goods Administration (TGA). It is also possible to
      prescribe unlicensed drugs under the TGA's special access scheme. A high rate of
      off-label prescribing has previously been reported in cancer. Our study aimed to
      document the disparity between evidence-based clinical guidelines for anticancer
      therapy, product approval and funding status of these agents within an academic
      tertiary/quaternary cancer centre. METHODS: All chemotherapy protocols approved
      for use in our specialist oncology centre were assessed to determine if the drugs
      were off-label or unlicensed for that indication based on review of their current
      product information. The Pharmaceutical Benefits Scheme (PBS) funding status for
      each protocol was subsequently assessed. RESULTS: A total of 448 protocols
      containing 82 different drugs across 15 tumour groups was identified. Overall,
      189 (42.2%) of protocols were off-label, and three (0.7%) were unlicensed. This
      resulted in all 192 protocols being unfunded by the PBS. Of the 189 off-label
      protocols, 132 (69.9%) were based on established evidence-based treatment
      guidelines, and a further 39 (20.6%) was based on phase II or III clinical trial
      data. CONCLUSION: Over 90% of off-label protocols are supported by established
      treatment guidelines or published peer-reviewed research even though the
      medications are not approved for that particular use by the TGA. However, these
      off-label protocols are unfunded by the PBS; this results in a marked inequality
      of access to appropriate medications for cancer patients across Australia.

PMID- 22372937
TI  - A 970 Hounsfield units (HU) threshold of kidney stone density on non-contrast
      computed tomography (NCCT) improves patients' selection for extracorporeal
      shockwave lithotripsy (ESWL): evidence from a prospective study.
AB  - What's known on the subject? and What does the study add? Stone density on non
      contrast computed tomography (NCCT) is reported to be a prognosis factor for
      extracorporeal shockwave lithotripsy (ESWL). In this prospective study, we
      determined that a 970 HU threshold of stone density is a very specific and
      sensitive threshold beyond which the likelihood to be rendered stone free is
      poor. Thus, NCCT evaluation of stone density before ESWL may useful to identify
      which patients should be offered alternative treatment to optimise their outcome.
      OBJECTIVE: * To evaluate the usefulness of measuring urinary calculi attenuation
      values by non-contrast computed tomography (NCCT) for predicting the outcome of
      treatment by extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: *
      We prospectively evaluated 50 patients with urinary calculi of 5-22 mm undergoing
      ESWL. * All patients had NCCT at 120 kV and 100 mA on a spiral CT scanner.
      Patient age, sex, body mass index, stone laterality, stone size, stone
      attenuation values (Hounsfield units [HU]), stone location, and presence of JJ
      stent were studied as potential predictors. * The outcome was evaluated 4 weeks
      after the ESWL session by NCCT. * ESWL success was defined as patients being
      stone-free (SF) or with remaining stone fragments of <4 mm, which were considered
      as clinically insignificant residual fragments (CIRF). RESULTS: * Our survey
      concluded that 26 patients (52%) were SF, 12 (24%) had CIRF and 12 (24%) had
      residual fragment on NCCT after a one ESWL treatment. * Stones of patients who
      became SF or had CIRF had a lower density compared with stones in patients with
      residual fragments [mean (sd) 715 (260) vs 1196 (171) HU, P < 0.001]. * The
      Youden Index showed that a stone density of 970 HU represented the most sensitive
      (100%) and specific (81%) point on the receiver-operating characteristic curve. *
      The stone-free rate for stones of <970 HU was 96% vs 38% for stones of >= 970 HU
      (P < 0.001). A linear relationship between the calculus density and the success
      rate of ESWL was identified. CONCLUSION: * The use of NCCT to determine the
      attenuation values of urinary calculi before ESWL helps to predict treatment
      outcome, and, consequently, could be helpful in planning alternative treatment
      for patients with a likelihood of a poor outcome from ESWL.

PMID- 22372938
TI  - Amniotic fluid inflammation with negative culture and outcome after cervical
      cerclage.
AB  - OBJECTIVE: To determine whether amniotic fluid (AF) inflammation, in the absence
      of infection, is associated with adverse pregnancy outcomes in nonelective
      cervical cerclage patients. METHODS: A retrospective case-control study was
      carried out. The patient population included 82 singleton pregnancies with
      negative AF cultures. The variables used to define AF inflammation were white
      blood cell count (WBC) >50 cell/mm(3), glucose <14 mg/dl or interleukin-6 (IL-6)
      >11.3 ng/ml. The study group consisted of cases with intra-amniotic inflammation.
      Sub-analysis was performed for the groups in which IL-6 concentrations were
      measured. Adverse outcomes were evaluated with variables such as gestational age
      at delivery, interval from cerclage to delivery, chorioamnionitis and cumulative
      neonatal morbidity. RESULTS: Elevated AF WBC was correlated with severe and
      extreme preterm delivery (p < 0.05). Decreased AF glucose was associated with
      histological chorioamnionitis and a decreased cerclage to delivery interval (p <
      0.05). Elevated AF IL-6 correlated significantly with decreased gestational age
      at delivery (p < 0.012) and decreased cerclage to delivery interval (p < 0.001).
      Elevated IL-6 concentrations were associated with severe, extreme preterm
      delivery (p < 0.001) and neonatal death (p < 0.001). CONCLUSION: Elevated AF IL
      6, elevated WBC and low AF glucose, in the absence of a positive AF culture, are
      significantly associated with adverse pregnancy outcomes in patients undergoing
      nonelective cerclage.

PMID- 22372939
TI  - Comparison of new Ampac bags and FireDebrisPAK(r) bags as packaging for fire
      debris analysis.
AB  - The FireDebrisPAK((r))  bags that were produced by Kapak were considered to be
      one of the best containers for fire debris. Kapak bags were discontinued;
      however, from July 2010, Ampac is offering a new packaging material. The aim of
      the presented research was to compare the properties (durability, background
      interferences, and permeability) of Kapak bags and packaging material offered by
      Ampac. The analysis was conducted by passive adsorption from the headspace with
      subsequent thermal desorption and analysis by GC-MS. The results proved that the
      properties of the compared materials are similar. Their greatest advantage is
      that they are impermeable for components of flammable liquids, so there is no
      danger of losing analytes or cross-contamination. Their one significant drawback
      is that they should not be exposed to temperatures above 80 degrees C. At this
      temperature, they become soft, their inner layer is compromised (becomes sticky),
      and they emit some volatile organic compounds. Among them, there are compounds
      that constitute the components of some of flammable liquids.

PMID- 22372940
TI  - Oxidation of highly unstable <4 nm diameter gold nanoparticles 850 mV negative of
      the bulk oxidation potential.
AB  - Here we describe the oxidation of <4 nm diameter Au nanoparticles (NPs) attached
      to indium tin oxide-coated glass electrodes in Br(-) and Cl(-) solution.
      Borohydride reduction of AuCl(4)(-) in the presence of hexanethiol or trisodium
      citrate (15 min) led to Au NPs <4 nm in diameter. After electrochemical and ozone
      removal of the hexanthiolate ligands from the thiol-coated Au NPs, Au oxidation
      peaks appeared in the range 0-400 mV vs Ag/AgCl (1 M KCl), which is 850-450 mV
      negative of the bulk Au oxidation peak near 850 mV. The oxidation potential of
      citrate-coated Au NPs is in the 300-500 mV range and those of 4 and 12 nm
      diameter Au NPs in the 660-780 mV range. The large negative shift in potential
      agrees with theory for NPs in the 1-2 nm diameter range. The oxidation potential
      of Au in Cl(-) solution is positive of that in Br(-) solution, but the difference
      decreases dramatically as the NP size decreases, showing less dependence on the
      halide for smaller NPs.

PMID- 22372941
TI  - Four multistate outbreaks of human Salmonella infections associated with live
      poultry contact, United States, 2009.
AB  - Outbreaks of human salmonellosis associated with live poultry contact have been
      reported since 1955. Multiple Salmonella serotypes have been associated with
      these outbreaks, and specific outbreak strains have been repeatedly linked to
      single hatcheries over multiple years. During 2009, four multistate outbreaks of
      human Salmonella infections associated with direct and indirect exposure to live
      poultry purchased from mail-order hatcheries and agricultural feed stores were
      identified, resulting in 165 culture-confirmed cases in 30 states. This report
      describes the epidemiologic, environmental and laboratory investigations
      conducted by state and local health departments, state departments of
      agriculture, the U.S. Department of Agriculture (USDA), Animal and Plant Health
      Inspection Service (APHIS), National Poultry Improvement Plan (NPIP) and National
      Veterinary Services Laboratories (NVSL), and the Centers for Disease Control and
      Prevention (CDC). Case-patients were identified through PulseNet, the national
      molecular subtyping network for foodborne disease surveillance, and interviewed
      using the CDC standard live poultry contact questionnaire that asks about poultry
      related exposures during the 7 days before illness onset. These outbreaks
      highlight the need to focus efforts on strategies to decrease and prevent human
      illness associated with live poultry contact through comprehensive interventions
      at the mail-order hatchery, agricultural feed store and consumer levels.
      Additional consumer education and interventions at mail-order hatcheries and
      venues where live poultry are sold, including agricultural feed stores, are
      necessary to prevent transmission of Salmonella from poultry to humans.

PMID- 22372942
TI  - Rapid molecular identification of Listeria species by use of real-time PCR and
      high-resolution melting analysis.
AB  - Identification of Listeria species via a molecular method is critical for food
      safety and clinical diagnosis. In this study, an assay integrating real-time
      quantitative PCR (Q-PCR) with high-resolution melting (HRM) curve analysis was
      developed and assessed for rapid identification of six Listeria species. The ssrA
      gene, which encodes a transfer-messenger RNA (tmRNA) is conserved and common to
      all bacterial phyla, contains a variable domain in Listeria spp. Therefore, Q-PCR
      and a HRM profile were applied to characterize this gene. Fifty-three Listeria
      species and 45 non-Listeria species were detected using one primer set, with an
      accuracy of 100% in reference to conventional methods. There was a 93.3%
      correction rate to 30 artificially contaminated samples. Thus, Q-PCR with melting
      profiling analysis proved able to identify Listeria species accurately.
      Consequently, this study demonstrates that the assay we developed is a functional
      tool for rapidly identifying six Listeria species, and has the potential for
      discriminating novel species food safety and epidemiological research.

PMID- 22372943
TI  - Analysis of the rotational structure in the high-resolution infrared spectrum of
      trans-hexatriene-1-13C1: a semiexperimental equilibrium structure for the C6
      backbone of trans-hexatriene.
AB  - trans-Hexatriene-1-(13)C(1) (tHTE-1-(13)C(1)) has been synthesized, and its high
      resolution (0.0015 cm(-1)) infrared spectrum has been recorded. The rotational
      structure in the C-type bands for nu(26) at 1011 cm(-1) and nu(30) at 894 cm(-1)
      has been analyzed. To the 1458 ground state combination differences from these
      bands, ground state rotational constants were fitted to a Watson-type Hamiltonian
      to give A(0) = 0.8728202(9), B(0) = 0.0435868(4), and C(0) = 0.0415314(2) cm(-1).
      Upper state rotational constants for the nu(30) band were also fitted.
      Predictions of the ground state rotational constants for tHTE-1-(13)C(1) from a
      B3LYP/cc-pVTZ model with scale factors based on the normal species were in
      excellent agreement with observations. Similar good agreement was found between
      predicted and observed ground state rotational constants for the three (13)C(1)
      isotopologues of cis-hexatriene, as determined from microwave spectroscopy.
      Equilibrium rotational constants for tHTE and its three (13)C(1) isotopologues,
      of which two were predicted, were used to find a semiexperimental equilibrium
      structure for the C(6) backbone of tHTE. This structure shows increased
      structural effects of pi-electron delocalization in comparison with butadiene and
      some differences from the cis isomer of HTE. Structures predicted with the MP2/cc
      pVTZ model are also compared.

PMID- 22372944
TI  - Investigation of the Listeria monocytogenes Scott A acid tolerance response and
      associated physiological and phenotypic features via whole proteome analysis.
AB  - The global proteomic responses of the foodborne pathogen Listeria monocytogenes
      strain Scott A, during active growth and transition to the stationary growth
      phase under progressively more acidic conditions, created by addition of lactic
      acid and HCl, were investigated using label-free liquid chromatography/tandem
      mass spectrometry. Approximately 56% of the Scott A proteome was quantitatively
      assessable, and the data provides insight into its acquired acid tolerance
      response (ATR) as well as the relation of the ATR to the growth phase transition.
      Alterations in protein abundance due to acid stress were focused in proteins
      belonging to the L. monocytogenes common genome, with few strain-dependent
      proteins involved. However, one of the two complete prophage genomes appeared to
      enter lysogeny. During progressive acidification, the growth rate and yield were
      reduced 55% and 98%, respectively, in comparison to nonacidified control
      cultures. The maintenance of the growth rate was determined to be connected to
      activation of cytoplasmic pH homeostatic mechanisms while cellular reproductive
      related and cell component turnover proteins were markedly more abundant in acid
      stressed cultures. Cell biomass accumulation was impeded predominantly due to
      repression of phosphodonor-linked enzymes involved with sugar phosphotransfer,
      glycolysis, and cell wall polymer biosynthesis. Acidification caused a shift from
      heterofermentation to an oxidatively stressed state in which ATP appears to be
      generated mainly through the pyruvate dehydrogenase/pyruvate
      oxidase/phosphotransacetylase/acetate kinase and branched chain acid
      dehydrogenase pathways. Analysis of regulons indicated energy conservation occurs
      due to repression by the GTP/isoleucine sensor CodY and also the RelA mediated
      stringent response. Whole proteome analysis proved to be an effective way to
      highlight proteins involved with the acquisition of the ATR.

PMID- 22372945
TI  - Measurement of family-centred care: translation, adaptation and validation of the
      Measure of Processes of Care (MPOC-56 and -20) for use in Japan.
AB  - BACKGROUND: The Measure of Processes of Care (MPOC) that was developed in Canada
      is a widely used quantitative measure of parents' perceptions of the extent to
      which family-centred care is conducted. The purpose of this study was to assess
      the validity and reliability of the Japanese version of the MPOC. METHODS: The
      translation of the MPOC was performed according to international standards for
      translation of questionnaires. The Canadian validation procedures were followed,
      consisting of concurrent validity, construct validity and test-retest
      reliability. The Japanese version of the MPOC was completed by 261 families with
      children receiving rehabilitation services. RESULTS: The Japanese version of the
      MPOC showed adequate internal consistency with Cronbach's alpha, varying between
      0.76 and 0.94. The construct validity was examined with confirmative analysis of
      each scale structure. Correlations between the MPOC scale scores and satisfaction
      questions scores were positive, and that to a question about parents' stress was
      negative. For test-retest reliability, the intraclass correlation coefficients
      were between 0.76 and 0.89. CONCLUSIONS: The Japanese version of the MPOC has
      good psychometric properties and can be recommended for evaluation of the
      processes of child rehabilitation in Japan.

PMID- 22372946
TI  - Complement activation in thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Ultra-large von Willebrand factor and deficiency of its cleaving
      protease are important factors in the events leading to thrombotic
      microangiopathy; however, the mechanisms involved are only partly understood.
      Whereas pathological activation of the alternative complement pathway is linked
      to atypical hemolytic uremic syndrome, the role of complement activation in
      thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was
      to investigate whether signs of complement activation are characteristic of TTP.
      PATIENTS AND METHODS: Twenty-three patients with TTP (18 women, median age 38
      years) and 17 healthy controls (13 women, median age 38 years) were included.
      Complement parameters (C3, Factors H, I, B and total alternative pathway
      activity) together with complement activation fragments (C3a) or complexes (C1rs
      INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti
      ADAMTS13 inhibitory antibodies were measured by the VWF-FRET73 assay. RESULTS:
      Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as
      compared with healthy controls. Decreased complement C3 levels indicative of
      complement consumption occurred in 15% of acute TTP patients. Significant
      decrease of complement activation products C3a and SC5b9 was observed during
      plasma exchange (PEX). The sustained presence of anti-ADAMTS13 inhibitory
      antibodies in complete remission was associated with increased complement
      activation. CONCLUSION: These data document in an observational study the
      presence of complement activation in TTP. Further investigation is needed to
      determine its potential pathogenetic significance.

PMID- 22372947
TI  - Starch filler and osmoprotectants improve the survival of rhizobacteria in dried
      alginate beads.
AB  - This work deals with optimising the cell survival of rhizobacteria encapsulated
      in alginate beads filled with starch. Immobilisation of rhizobacteria was done by
      dripping alginate-starch solution mixed with rhizobacteria into a calcium
      solution. Beads were analysed based on matrix formulation, bacteria growth phase,
      osmoprotectants and nature of calcium solution. Maximum cell recovery was
      obtained on Raoultella terrigena grown in medium supplemented with trehalose and
      calcium gluconate as gelling agent. Furthermore, dried beads containing
      Azospirillum brasilense presented 76% of viable cells after one year of storage.
      The survival of rhizobacteria during the bioencapsulation process can be improved
      by incorporating starch on beads composition, varying the growth phase of cells
      and using trehalose in growth culture medium. This work provides a selection of
      appropriate methods to improve the surviving rate of encapsulated cells during
      their production and long-term storage (~1 year at 4 degrees C).

PMID- 22372948
TI  - Eczema among adults: prevalence, risk factors and relation to airway diseases.
      Results from a large-scale population survey in Sweden.
AB  - BACKGROUND: In contrast to asthma and rhinitis, few studies among adults
      investigating the prevalence and risk factors of eczema have been published.
      OBJECTIVES: To investigate the prevalence and risk factors of eczema among adults
      in West Sweden. A further aim was to study the associations between asthma,
      rhinitis and eczema. METHODS: A questionnaire on respiratory health was mailed in
      2008 to 30,000 randomly selected subjects in West Sweden aged 16-75 years; 62%
      responded. The questionnaire included questions about eczema, respiratory
      symptoms and diseases and their possible determinants. A subgroup of 669 subjects
      underwent skin prick testing against common airborne allergens. RESULTS: 'Eczema
      ever' was reported by 40.7% and 'current eczema' by 11.5%. Both conditions were
      significantly more common among women. The prevalence decreased with increasing
      age. The coexistence of both asthma and rhinitis with eczema was common. The main
      risk factors were family history of allergy and asthma. The dominant
      environmental risk factor was occupational exposure to gas, dust or fumes.
      Smoking increased the risk. Eczema was associated with urbanization, while
      growing up on a farm was associated with a decreased risk. Added one by one to
      the multivariate model, asthma, allergic rhinitis and any positive skin prick
      test were associated with eczema. CONCLUSIONS: Eczema among adults is a common
      disease with more women than men having and having had eczema. Eczema is
      associated with other atopic diseases and with airway symptoms. Hereditary
      factors and exposure to gas, dust and fumes are associated with eczema.

PMID- 22372949
TI  - The effect of the delivery carrier on the quality of bone formed via bone
      morphogenetic protein-2.
AB  - Bone morphogenetic protein-2 (BMP-2) can induce bone generation in vivo. Although
      many studies have demonstrated an increased quantity of regenerated bone after
      the delivery of BMP-2 using various carriers, little is known about the effect of
      the carrier type on the quality of the regenerated bone. In this study, we
      compared the quality of regenerated bone when BMP-2 was delivered with either
      beta-tricalcium phosphate (beta-TCP) or heparin-conjugated fibrin (HCF), both of
      which are shown to be excellent carriers for BMP-2. The profile of the release of
      BMP-2 was not significantly different between the delivery carriers. However, the
      alkaline phosphate activity of cultured osteoblasts was significantly higher when
      BMP-2 was delivered using HCF than when BMP-2 was delivered using beta-TCP. To
      evaluate the quality of the regenerated bone, both types of BMP-2 carriers were
      implanted into critical-sized calvarial defects in mice. Eight weeks after
      implantation, the regenerated bone was examined by histomorphometry. Importantly,
      the treatment using HCF + BMP-2 and beta-TCP + BMP-2 resulted in similar bone
      formation areas. However, the treatment using HCF + BMP-2 resulted in
      significantly higher bone density than the treatment using beta-TCP + BMP-2. This
      study shows that a BMP-2 delivery carrier can modulate the quality of bone
      regenerated via BMP-2 delivery.

PMID- 22372950
TI  - Rbms3, an RNA-binding protein, mediates the expression of Ptf1a by binding to its
      3'UTR during mouse pancreas development.
AB  - The development of the pancreas is a complicated process that is regulated on
      several levels. Pancreas transcription factor 1, alpha subunit (Ptf1a), also
      known as p48, is a pancreas-specific basic helix-loop-helix transcription factor
      that is critical for both exocrine pancreas development and maintenance of acinar
      cell differentiation. Based on a differential screening assay, we identified
      Rbms3, a gene encoding a glycine-rich RNA-binding protein, to be specifically
      expressed in the neural tube and the pancreatic rudiment of e10.5 embryos. The
      presence of Rbms3 in the early developing pancreas suggests that specific post
      transcriptional regulation mechanisms play an important role in controlling
      pancreas development. In this study, we show that Rbms3 binds to the 3'UTR of
      Ptf1a mRNA, but not the 3'UTR of Pdx1, which is another pancreatic transcription
      factor. The ectopic expression of Rbms3 stimulates the translation of a reporter
      gene carrying the Ptf1a 3'UTR. In addition, when Rbms3 expression is suppressed
      in the AR42J-B13 pancreatic exocrine cell line, the expression of Ptf1a is also
      down-regulated. These results suggest that binding of Rbms3 to the 3'UTR of Ptf1a
      regulates the production of the Ptf1a protein and, thereby, indirectly regulates
      the expression of the Ptf1a downstream target genes.

PMID- 22372951
TI  - Ciliary neurotrophic factor stimulates tyrosine hydroxylase activity.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in norepinephrine
      synthesis, and its expression and activity are regulated by many factors in
      sympathetic neurons. Cytokines that act through gp130, such as ciliary
      neurotrophic factor (CNTF) decrease norepinephrine production in sympathetic
      neurons by suppressing TH mRNA and stimulating degradation of TH protein, leading
      to the loss of enzyme. Their effect on the activity of TH is unclear, but recent
      in vivo observations suggest that cytokines may stimulate TH activity. We
      investigated this issue by quantifying TH protein levels and activity in cultured
      sympathetic neurons. We also examined the state of TH phosphorylation on serine
      31 and 40, sites known to affect TH activity and degradation. We found that CNTF,
      acting through gp130, stimulated the rate of l-3,4-dihydroxyphenylalanine
      production while at the same time decreasing TH enzyme levels, thereby increasing
      the specific activity of the enzyme. We also found that phosphorylation of TH on
      Ser31 was increased, and phosphorylation on Ser40 was decreased, after four days
      of CNTF exposure. Our data are consistent with previous findings that Ser31
      phosphorylation stimulates TH activity, whereas Ser40 phosphorylation can target
      TH for proteasomal degradation.

PMID- 22372953
TI  - Lipid conjugated oligonucleotides: a useful strategy for delivery.
AB  - Oligonucleotides, including antisense oligonucleotides and siRNA, are promising
      therapeutic agents against a variety of diseases. Effective delivery of these
      molecules is critical in view of their clinical application. Therefore, cation
      based nanoplexes have been developed to improve the stability as well as the
      intracellular penetration of these short fragments of nucleic acids. However,
      this approach is clearly limited by the strong interaction with proteins after
      administration and by the inherent toxicity of these positively charged
      transfection materials. Neutral lipid-oligonucleotide conjugates have become a
      subject of considerable interest to improve the safe delivery of
      oligonucleotides. These molecules have been chemically conjugated to hydrophobic
      moieties such as cholesterol, squalene, or fatty acids to enhance their
      pharmacokinetic behavior and trans-membrane delivery. The present review gives an
      account of the main synthetic methods available to conjugate lipids to
      oligonucleotides and will discuss the pharmacological efficacy of this approach. 

PMID- 22372954
TI  - A prospective and controlled in vivo study to determine if acute episodes of high
      glucose concentrations in the extra-embryonic celomic cavity could be related to
      spontaneous abortion.
AB  - OBJECTIVES: In vitro preparations have provided evidence suggesting that acute
      and chronic exposure to very high glucose concentrations can lead to embryonic
      demise via disruption of the extra-celomic membranes and yolk sac. In this study,
      we sought to determine, in vivo, if an acute increase in extra-embryonic fluid
      glucose concentration could cause spontaneous abortion. MATERIALS AND METHODS: We
      employed a pregnant non-human primate model and ultrasound-guided celocentesis at
      38-42 days from conception. In three control animals, partial replacement of the
      extra-embryonic celomic fluid was performed using normal saline containing 0.6
      mg/mL of glucose. In four study animals, the extra-celomic fluid was replaced
      with a similar solution containing high glucose concentrations. All animals were
      then followed until delivery. RESULTS: Immediately after celocentesis, the
      estimated celomic fluid glucose concentration in experimental animals ranged
      between 5 mg/mL and 83.8 mg/mL (8-140 times the physiologic glucose concentration
      of 0.6 mg/mL). All animals delivered live newborns at term without congenital
      abnormalities. CONCLUSIONS: These findings suggest that transitory increases in
      the extra-celomic fluid glucose concentration are not likely to cause a
      spontaneous abortion detectable with the sample size of our study.

PMID- 22372955
TI  - Cell cycle phase classification in 3D in vivo microscopy of Drosophila
      embryogenesis.
AB  - BACKGROUND: Cell divisions play critical roles in disease and development. The
      analysis of cell division phenotypes in high content image-based screening and
      time-lapse microscopy relies on automated nuclear segmentation and classification
      of cell cycle phases. Automated identification of the cell cycle phase helps
      biologists quantify the effect of genetic perturbations and drug treatments. Most
      existing studies have dealt with 2D images of cultured cells. Few, if any,
      studies have addressed the problem of cell cycle classification in 3D image
      stacks of intact tissues. RESULTS: We developed a workflow for the automated cell
      cycle phase classification in 3D time-series image datasets of live Drosophila
      embryos expressing the chromatin marker histone-GFP. Upon image acquisition by
      laser scanning confocal microscopy and 3D nuclear segmentation, we extracted 3D
      intensity, shape and texture features from interphase nuclei and mitotic
      chromosomes. We trained different classifiers, including support vector machines
      (SVM) and neural networks, to distinguish between 5 cell cycles phases
      (Interphase and 4 mitotic phases) and achieved over 90% accuracy. As the
      different phases occur at different frequencies (58% of samples correspond to
      interphase), we devised a strategy to improve the identification of classes with
      low representation. To investigate which features are required for accurate
      classification, we performed feature reduction and selection. We were able to
      reduce the feature set from 42 to 9 without affecting classifier performance. We
      observed a dramatic decrease of classification performance when the training and
      testing samples were derived from two different developmental stages, the nuclear
      divisions of the syncytial blastoderm and the cell divisions during gastrulation.
      Combining samples from both developmental stages produced a more robust and
      accurate classifier. CONCLUSIONS: Our study demonstrates that automated cell
      cycle phase classification, besides 2D images of cultured cells, can also be
      applied to 3D images of live tissues. We could reduce the initial 3D feature set
      from 42 to 9 without compromising performance. Robust classifiers of intact
      animals need to be trained with samples from different developmental stages and
      cell types. Cell cycle classification in live animals can be used for automated
      phenotyping and to improve the performance of automated cell tracking.

PMID- 22372956
TI  - Terpenoids from Chloranthus serratus and their anti-inflammatory activities.
AB  - Seven new terpenoids, including two sesquiterpene dimers (1, 2), two
      norditerpenoids (3, 4), and three sesquiterpenes (5-7), along with six known
      sesquiterpene dimers and four known sesquiterpenes were isolated from the whole
      plant of Chloranthus serratus. Their structures and relative configurations were
      elucidated on the basis of spectroscopic data analysis. The absolute
      configuration of 1 was determined by the CD exciton chirality method. These
      isolates were evaluated for their inhibitory effects on lipopolysaccharide
      induced nitric oxide production in RAW264.7 cells. Compound 2 and two known
      compounds, shizukaols B and D, showed significant anti-inflammatory activities,
      with IC(50) values of 0.22, 0.15, and 7.22 MUM, respectively.

PMID- 22372958
TI  - Finding consistent disease subnetworks across microarray datasets.
AB  - BACKGROUND: While contemporary methods of microarray analysis are excellent tools
      for studying individual microarray datasets, they have a tendency to produce
      different results from different datasets of the same disease. We aim to solve
      this reproducibility problem by introducing a technique (SNet). SNet provides
      both quantitative and descriptive analysis of microarray datasets by identifying
      specific connected portions of pathways that are significant. We term such
      portions within pathways as "subnetworks". RESULTS: We tested SNet on independent
      datasets of several diseases, including childhood ALL, DMD and lung cancer. For
      each of these diseases, we obtained two independent microarray datasets produced
      by distinct labs on distinct platforms. In each case, our technique consistently
      produced almost the same list of significant nontrivial subnetworks from two
      independent sets of microarray data. The gene-level agreement of these
      significant subnetworks was between 51.18% to 93.01%. In contrast, when the same
      pairs of microarray datasets were analysed using GSEA, t-test and SAM, this
      percentage fell between 2.38% to 28.90% for GSEA, 49.60% tp 73.01% for t-test,
      and 49.96% to 81.25% for SAM. Furthermore, the genes selected using these
      existing methods did not form subnetworks of substantial size. Thus it is more
      probable that the subnetworks selected by our technique can provide the
      researcher with more descriptive information on the portions of the pathway
      actually affected by the disease. CONCLUSIONS: These results clearly demonstrate
      that our technique generates significant subnetworks and genes that are more
      consistent and reproducible across datasets compared to the other popular methods
      available (GSEA, t-test and SAM). The large size of subnetworks which we generate
      indicates that they are generally more biologically significant (less likely to
      be spurious). In addition, we have chosen two sample subnetworks and validated
      them with references from biological literature. This shows that our algorithm is
      capable of generating descriptive biologically conclusions.

PMID- 22372959
TI  - The B7 homologues and their receptors in hematologic malignancies.
AB  - The B7 homologues and their receptors regulate both peripheral tolerance and
      adaptive immunity. This field is rapidly evolving as new ligands and receptors
      are being identified. Much of the work supporting their role in the regulation of
      host anti-tumor immunity has been derived from experimental models and clinical
      trials in solid malignancies. However, a growing body of evidence demonstrates
      that the B7-H family has important immunologic and non-immunologic functions in a
      variety of hematologic malignancies. Herein, we will review recent evidence that
      supports the therapeutic targeting of the B7 homologues in hematologic
      malignancies.

PMID- 22372960
TI  - Prediction of eye color from genetic data using Bayesian approach.
AB  - Prediction of visible traits from genetic data in certain forensic cases may
      provide important information that can speed up the process of investigation.
      Research that has been conducted on the genetics of pigmentation has revealed
      polymorphisms that explain a significant proportion of the variation observed in
      human iris color. Here, on the basis of genetic data for the six most relevant
      eye color predictors, two alternative Bayesian network model variants were
      developed and evaluated for their accuracy in prediction of eye color. The first
      model assumed eye color to be categorized into blue, brown, green, and hazel,
      while the second variant assumed a simplified classification with two states:
      light and dark. It was found that particularly high accuracy was obtained for the
      second model, and this proved that reliable differentiation between light and
      dark irises is possible based on analysis of six single nucleotide polymorphisms
      and a Bayesian procedure of evidence interpretation.

PMID- 22372961
TI  - A new, simple implant-level impression technique for dental implants in limited
      interproximal space.
AB  - Making an implant-level impression when implants are placed in limited
      interproximal space or compromising angulations can be a time-consuming
      procedure. This article presents a new method for developing a master cast for
      two implants clinically placed convergent and very close to each other. The
      technique consists of making an implant-level impression using a transfer jig
      fabricated on dental abutments.

PMID- 22372962
TI  - Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia
      orange essential oil on methicillin-resistant Staphylococcus aureus.
AB  - AIMS: The objectives of this study were to evaluate the antistaphylococcal effect
      and elucidate the mechanism of action of orange essential oil against antibiotic
      resistant Staphylococcus aureus strains. METHODS AND RESULTS: The inhibitory
      effect of commercial orange essential oil (EO) against six Staph. aureus strains
      was tested using disc diffusion and agar dilution methods. The mechanism of EO
      action on MRSA was analysed by transcriptional profiling. Morphological changes
      of EO-treated Staph. aureus were examined using transmission electron microscopy.
      Results showed that 0.1% of terpeneless cold-pressed Valencia orange oil (CPV)
      induced the cell wall stress stimulon consistent with the inhibition of cell wall
      synthesis. Transmission electron microscopic observation revealed cell lysis and
      suggested a cell wall lysis-related mechanism of CPV. CONCLUSIONS: CPV inhibits
      the growth of Staph. aureus, causes gene expression changes consistent with the
      inhibition of cell wall synthesis, and triggers cell lysis. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Multiple antibiotics resistance is becoming a serious
      problem in the management of Staph. aureus infections. In this study, the altered
      expression of cell wall-associated genes and subsequent cell lysis in MRSA caused
      by CPV suggest that it may be a potential antimicrobial agent to control
      antibiotic-resistant Staph. aureus.

PMID- 22372963
TI  - Inhibition of stretching-evoked ATP release from bladder mucosa by
      anticholinergic agents.
AB  - OBJECTIVE: To determine whether muscarinic receptor antagonism affects stretching
      induced release of ATP. MATERIALS AND METHODS: Mucosal strips, dissected from
      guinea pig (male, 450g; n = 10) urinary bladders, were placed in horizontal organ
      baths and superfused with Ca(2+) -free Tyrode's solution. Superfusate samples
      were taken pre- and post- intervention (rapid stretching or relaxation) and ATP
      concentration was quantified using a luciferin-luciferase assay. The effect of
      muscarinic acetylcholine receptor antagonism on ATP release was assessed by
      addition of methoctramine (1 uM) and 4-DAMP (10 nM). RESULTS: Rapid stretching (0
      to 13.3 +/- 1.2 mN; no. strips = 20) increased ATP in the superfusate to a median
      threefold increase over basal levels. After a period of equilibration, tension in
      the mucosal strips relaxed until it had reached a new steady-state after 60 min
      and stretching was repeated. In the presence of 4-DAMP (10 nM) or methoctramine
      (1 uM), ATP concentrations after stretching reduced to 61% or 20%, respectively.
      By contrast, ATP concentrations in mucosa-matched controls, perfused with
      vehicle, increased in response to stretching by 391% and 1500%, respectively.
      Rapid relaxation also stimulated ATP release. This release did not appear to be
      sensitive to 4-DAMP or methoctramine. CONCLUSIONS: An alteration of resting
      mucosal tension is the key determinant of ATP release, as ATP is released from
      the mucosa in response to both stretching and relaxation. Muscarinic receptor
      antagonism inhibits stretching-evoked ATP release from bladder mucosa, suggesting
      that anticholinergic agents used to treat human lower urinary tract pathologies
      act on urothelial muscarinic receptors.

PMID- 22372964
TI  - Towards a vaccine for chronic obstructive pulmonary disease.
AB  - This review discusses chronic obstructive pulmonary disease as an outcome of two
      pathogenic pathways: the first resulting from inhalation of toxins and the second
      a consequence of bacterial colonisation of damaged airways. Earlier assessment of
      the role played by bacteria in acute exacerbations was compromised by a
      deficiency of quality data and the use of parameters more relevant to invasive
      infection. Data are reviewed to support a hypothesis that states intrabronchial
      inflammation reflects an excessive and inappropriate host response (largely
      mediated by Th17 cells derived from gut-associated lymphoid tissues) to
      colonising bacteria acting as an 'antigen sump' (in essence, a hypersensitivity
      reaction). It is proposed that both viral and bacterial infections exacerbate
      inflammation through a common pathway that involves colonising bacteria. An oral
      vaccine containing inactivated non-typeable Haemophilus influenzae augments a
      protective loop that involves the aspiration of bronchus content into the gut and
      reduces the severity of acute exacerbations including the need for hospital
      admission by reducing the 'load' of bacteria comprising this final common path.
      The positive clinical results from trials using oral NTHi support both the
      concept that bacterial colonisation of damaged airways is a potent second
      pathogenic pathway and that oral immunotherapy provides a significant therapeutic
      advance in limiting damage in chronic obstructive pulmonary disease.

PMID- 22372965
TI  - Detection of CC17 Enterococcus faecium in dogs and a comparison with human
      isolates.
AB  - Enterococcus faecium strains of clonal complex (CC) 17 were isolated from
      domestic dogs. The strains were more prevalent in infectious isolates than in
      colonized isolates, suggesting that strains of the CC17 lineage may have an
      advantage in causing infections in dogs. The pulsed field gel electrophoresis
      patterns of some dog and human isolates were over 90% similar. However,
      antimicrobial resistance patterns and virulence factors were not identical, which
      might reflect different use of antimicrobials in veterinary medicine or in host
      specificity.

PMID- 22372966
TI  - Do larger pictorial health warnings diminish the need for plain packaging of
      cigarettes?
AB  - AIMS: To assess the effects on brand appeal of plain packaging and size of
      pictorial health warnings (PHWs). DESIGN: Three (30%, 70% and 100% size front-of
      pack PHWs) by two (branded versus plain) between-subjects online experiment.
      SETTING: Australia. PARTICIPANTS: A total of 1203 adult smokers. MEASUREMENTS:
      Rating of cigarette brands, smoking attitudes and intentions, purchase intent.
      FINDINGS: Compared to branded packs, plain packs reduced smokers' ratings of
      'positive pack characteristics' (P < 0.001), 'positive smoker characteristics' (P
      < 0.001) and 'positive taste characteristics' (P = 0.039). Plain packs were rated
      as being smoked by people who were more 'boring' than those who smoked branded
      packs (P = 0.001). By contrast, increasing size of PHW above 30% only reduced
      ratings of 'positive pack characteristics' (P = 0.001), but also decreased
      ratings of smokers as being 'boring' (P = 0.027). Plainness and size of PHW
      interacted in predicting ratings of 'positive pack characteristics' (P = 0.008),
      so that when packs were plain, increasing the size of PHW above 30% did not
      further reduce ratings. Presentation of only plain packs increased the likelihood
      that smokers would not choose to purchase any pack (20.3%) compared to
      presentation of only branded packs (15.3%) (odds ratio = 1.4; P = 0.026), while
      size of PHWs had no influence upon purchase choice. CONCLUSIONS: Plain packaging
      probably plays a superior role in undermining brand appeal and purchase intent to
      increasing health warning size. Policymakers should not rely solely upon large
      health warnings, which are designed primarily to inform consumers about smoking
      harms, to also reduce brand appeal: both strategies are likely to be required.

PMID- 22372967
TI  - Development, evaluation and application of 3D QSAR Pharmacophore model in the
      discovery of potential human renin inhibitors.
AB  - BACKGROUND: Renin has become an attractive target in controlling hypertension
      because of the high specificity towards its only substrate, angiotensinogen. The
      conversion of angiotensinogen to angiotensin I is the first and rate-limiting
      step of renin-angiotensin system and thus designing inhibitors to block this step
      is focused in this study. METHODS: Ligand-based quantitative pharmacophore
      modeling methodology was used in identifying the important molecular chemical
      features present in the set of already known active compounds and the missing
      features from the set of inactive compounds. A training set containing 18
      compounds including active and inactive compounds with a substantial degree of
      diversity was used in developing the pharmacophore models. A test set containing
      93 compounds, Fischer randomization, and leave-one-out methods were used in the
      validation of the pharmacophore model. Database screening was performed using the
      best pharmacophore model as a 3D structural query. Molecular docking and density
      functional theory calculations were used to select the hit compounds with strong
      molecular interactions and favorable electronic features. RESULTS: The best
      quantitative pharmacophore model selected was made of one hydrophobic, one
      hydrogen bond donor, and two hydrogen bond acceptor features with high a
      correlation value of 0.944. Upon validation using an external test set of 93
      compounds, Fischer randomization, and leave-one-out methods, this model was used
      in database screening to identify chemical compounds containing the identified
      pharmacophoric features. Molecular docking and density functional theory studies
      have confirmed that the identified hits possess the essential binding
      characteristics and electronic properties of potent inhibitors. CONCLUSION: A
      quantitative pharmacophore model of predictive ability was developed with
      essential molecular features of a potent renin inhibitor. Using this
      pharmacophore model, two potential inhibitory leads were identified to be used in
      designing novel and future renin inhibitors as antihypertensive drugs.

PMID- 22372968
TI  - The experience of disabled children as inpatients: a structured review and
      synthesis of qualitative studies reporting the views of children, parents and
      professionals.
AB  - Disabled children are a broad group that includes those with complex, special or
      additional health needs as a result of chronic physical, cognitive, communication
      or behavioural problems. These children are more frequently admitted to hospital
      than other children; however, there appears to be relatively little research on
      their experience as inpatients. The aim of this structured review and synthesis
      was to integrate findings from qualitative studies reporting the experience of
      disabled children when they are hospital inpatients. Inclusion criteria were:
      qualitative studies that focused on the experience of children less than 18 years
      old, with a chronic health condition or neurodisability, during an inpatient
      stay. Studies of outpatient episodes or intensive care units were excluded. A
      systematic search identified relevant abstracts, selected papers were reviewed
      and data were extracted. The synthesis involved elucidating and integrating
      common themes. Eight relevant papers were identified; data were gathered from
      children, parents and staff. Communication between children and staff was a
      dominant theme and comprised giving the child information about their condition
      and appropriate involvement of the child/young person in discussions and decision
      making that affected them. Also important was communication between parents and
      staff, particularly around the division of care for their child. Other themes
      included emotions, particularly fears, the ward environment and confidence in
      staff. The review suggests that disabled children's experience as inpatients is
      not always optimal. Improving the communication skills of ward staff and
      providing information to disabled children and their families would improve
      disabled children's experience when they are inpatients.

PMID- 22372969
TI  - High accuracy measurements of OH reaction rate constants and IR absorption
      spectra: substituted 2-propanols.
AB  - Rate constants for the gas phase reactions of OH radicals with 2-propanol and
      three fluorine substituted 2-propanols, (CH(3))(2)CHOH (k(0)), (CF(3))(2)CHOH
      (k(1)), (CF(3))(2)C(OH)CH(3) (k(2)), and (CF(3))(3)COH (k(3)), were measured
      using a flash photolysis resonance-fluorescence technique over the temperature
      range 220-370 K. The Arrhenius plots were found to exhibit noticeable curvature
      for all four reactions. The temperature dependences of the rate constants can be
      represented by the following expressions: k(0)(T) = 1.46 * 10(-11) exp{-883/T} +
      1.30 * 10(-12) exp{+371/T} cm(3) molecule(-1) s(-1); k(1)(T) = 1.19 * 10(-12)
      exp{-1207/T} + 7.85 * 10(-16) exp{+502/T } cm(3) molecule(-1) s(-1); k(2)(T) =
      1.68 * 10(-12) exp{-1718/T} + 7.32 * 10(-16) exp{+371/T} cm(3) molecule(-1) s(
      1); k(3)(T) = 3.0 * 10(-20) * (T/298)(11.3) exp{+3060/T} cm(3) molecule(-1) s(
      1). The atmospheric lifetimes due to reactions with tropospheric OH were
      estimated to be 2.4 days and 1.9, 6.3, and 46 years, respectively. UV absorption
      cross sections were measured between 160 and 200 nm. The IR absorption cross
      sections of the three fluorinated compounds were measured between 450 and 1900
      cm(-1), and their global warming potentials were estimated.

PMID- 22372970
TI  - Development and structural validation of a shortened version of the Participation
      Scale.
AB  - PURPOSE: To validate a shortened version of the Participation Scale (P-scale)
      that will be quicker to use and to describe the factor structure found in the P
      scale data in various study samples. METHODS: A large multi-country and multi
      cultural database was compiled consisting of 5125 respondents. Item analysis,
      explanatory factor analysis and confirmatory factor analysis were applied to
      identify items for deletion and investigate the factor structure of the P-scale.
      RESULTS: The multi-country database included 11 databases from six different
      countries. Respondents were affected by a range of health conditions, including
      leprosy, HIV/AIDS, dermatological conditions and various disabilities. Of the
      respondents included 57% were male. The P-scale Short (PSS) contains 13 items. A
      two-factor structure, with factors named "work-related participation" (three
      items) and "general participation" (10 items), showed the best model fit
      (Comparative Fit Index = 0.983, Tucker Lewis Index = 0.979, Rooted Mean Square
      Error of Approximation = 0.061). The Cronbach's alphas were very good for both
      the whole scale and the subscales, 0.91, 0.83 and 0.90, respectively. Correlation
      between the two factors was high (r = 0.75) indicating that interpreting the P
      scale as measuring an overall factor "participation" is still valid. A very high
      correlation (r = 0.99) was found between the full P-scale and the PSS.
      CONCLUSIONS: The findings suggest good validity of the P-scale across a range of
      languages and cultures. However, field testing needs to confirm the validity of
      the PSS to measure the level of social participation restrictions across cultures
      and health conditions.

PMID- 22372971
TI  - Low-dose electron beam radiation and romidepsin therapy for symptomatic cutaneous
      T-cell lymphoma lesions.
AB  - BACKGROUND: Romidepsin is a structurally unique histone deacetylase inhibitor
      approved by the U.S. Food and Drug Administration for therapy of relapsed or
      refractory cutaneous T-cell lymphoma (CTCL). Localized electron beam radiation
      therapy (LEBT) is standard practice in the care of patients with chronically
      traumatized and painful lesions. Combination therapy of those two modalities may
      be beneficial for the therapy of CTCL. OBJECTIVES: To report observations on
      supportive LEBT utilized for isolated refractory lesions in patients on
      romidepsin. METHODS: Observations were made during a phase II clinical trial
      sponsored by the National Cancer Institute (NCI-1312) examining the efficacy of
      romidepsin for patients with relapsed, refractory or advanced CTCL, stage IB-IVA
      mycosis fungoides (MF) or Sezary syndrome. Skin responses were assessed by
      evaluation of five target lesions only. Patients with objective clinical
      responses in target lesions who had symptomatic nontarget lesions were allowed
      limited LEBT to isolated lesions for symptomatic relief. Patients who received
      localized radiation were not considered complete responders at any point.
      RESULTS: Five patients with advanced MF (three stage IIB and two stage IVA2)
      received LEBT to symptomatic nontarget lesions while on a protocol with
      romidepsin. None of these patients experienced additional or unexpected toxicity.
      Four of the five patients demonstrated fast and durable responses. We noted that
      significantly lower than standard doses of LEBT effectively treated symptomatic
      lesions in these patients. CONCLUSIONS: LEBT demonstrated significant responses
      at very low doses without additional toxicity in patients on protocol treatment
      with the histone deacetylase inhibitor romidepsin. This merits formal
      investigation in a clinical trial for potential synergy in patients with CTCL.

PMID- 22372973
TI  - Novel allergen from the freshwater clam and the related allergy.

PMID- 22372972
TI  - Use of a mouse model to elucidate the phenotypic effects of the von Willebrand
      factor cleavage mutants, Y1605A/M1606A and R1597W.
AB  - BACKGROUND: von Willebrand Factor (VWF) is tightly regulated by the
      metalloproteinase ADAMTS13, which cleaves VWF to reduce VWF multimer size and
      binding affinity for collagen and platelets. OBJECTIVE: This study examines two
      VWF mutations, R1597W (enhanced cleavage) and Y1605A-M1606A (decreased cleavage),
      to determine their impact on VWF, in addition to ADAMTS13-mediated cleavage.
      METHODS: In vitro mouse ADAMTS13 digestions were performed on recombinant
      proteins. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA,
      following which VWF antigen, multimer profile and VWF propeptide levels were
      determined. A ferric chloride injury model of thrombosis was also evaluated.
      RESULTS: In vitro ADAMTS13 digestion of full-length mouse VWF required > 97-fold
      higher ADAMTS13 levels for Y1605A/M1606A, and 68% lower ADAMTS13 levels for
      R1597W compared with wild type. In vivo, R1597W had reduced VWF:Ag and both
      mutations exhibited increased VWF propeptide/VWF:Ag ratios. R1597W multimers show
      a lower molecular weight profile compared with wild type and Y1605A/M1606A mice.
      When co-injected with Adamts13 cDNA, Y1605A/M1606A multimers were larger compared
      with wild type, and R1597W showed only a single multimer band and decreased
      clearance via VWFpp/VWF:Ag ratio. R1597W was associated with reduced thrombus
      formation but normal platelet accumulation in a ferric chloride injury model
      while Y1605A/M1606A had a loss of occlusive thrombi but increased platelet
      accumulation compared with wild type. CONCLUSIONS: This study demonstrates that
      mutations that alter ADAMTS13 cleavage also can affect VWF clearance, VWF antigen
      level, multimer structure and thrombotic potential in the VWF knockout
      hydrodynamic injection model.

PMID- 22372974
TI  - Influence of children's oral health-related quality of life on school performance
      and school absenteeism.
AB  - OBJECTIVE: This study assessed the relation of child oral health-related quality
      of life with school performance and school absenteeism. METHODS: We followed a
      cross-sectional design with a multistage random sample of 312 12-year-old
      schoolchildren living in Brazil. The participants completed the child perceptions
      questionnaire (CPQ(11-14) ) that provides information about psychological
      factors, while their parents or guardians answered questions on their
      socioeconomic status measured by parents' education level and household income. A
      dental examination of each child provided information on the prevalence of caries
      and dental trauma. Data on school performance, which included the results of
      baseline Brazilian language (Portuguese) tests, and school absenteeism (school
      days missed) were obtained from the school register. Multilevel linear regression
      was used to investigate the association among psychological and socioeconomic
      status and children's school performance. RESULTS: In the multiple model, after
      adjusting for individual covariates, being a girl was associated with higher
      school performance (P < 0.05), whereas low household income (P < 0.05), higher
      mean of CPQ(11-14) (P < 0.05), and higher school days missed (P < 0.001) were
      identified as individual determinants of lower school performance. When the
      school-level covariates were included in the model, the association between
      subjects' level characteristics and school performance still persisted.
      CONCLUSION: Children's school performance and absence were influenced by
      psychological and socioeconomic conditions.

PMID- 22372975
TI  - Transparent mediation-based access to multiple yeast data sources using an
      ontology driven interface.
AB  - BACKGROUND: Saccharomyces cerevisiae is recognized as a model system representing
      a simple eukaryote whose genome can be easily manipulated. Information solicited
      by scientists on its biological entities (Proteins, Genes, RNAs...) is scattered
      within several data sources like SGD, Yeastract, CYGD-MIPS, BioGrid, PhosphoGrid,
      etc. Because of the heterogeneity of these sources, querying them separately and
      then manually combining the returned results is a complex and time-consuming task
      for biologists most of whom are not bioinformatics expert. It also reduces and
      limits the use that can be made on the available data. RESULTS: To provide
      transparent and simultaneous access to yeast sources, we have developed YeastMed:
      an XML and mediator-based system. In this paper, we present our approach in
      developing this system which takes advantage of SB-KOM to perform the query
      transformation needed and a set of Data Services to reach the integrated data
      sources. The system is composed of a set of modules that depend heavily on XML
      and Semantic Web technologies. User queries are expressed in terms of a domain
      ontology through a simple form-based web interface. CONCLUSIONS: YeastMed is the
      first mediation-based system specific for integrating yeast data sources. It was
      conceived mainly to help biologists to find simultaneously relevant data from
      multiple data sources. It has a biologist-friendly interface easy to use. The
      system is available at http://www.khaos.uma.es/yeastmed/.

PMID- 22372976
TI  - Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study.
AB  - OBJECTIVES: The P2Y(12) inhibitor clopidogrel inhibits platelet aggregation and
      is used in the treatment and prevention of coronary artery disease. It is widely
      used and, in combination with acetylsalicylic acid, is the standard of care for
      acute coronary syndrome and percutaneous coronary intervention. The mode of
      action of clopidogrel involves pathways that are important to the metabolic
      activity in bone cells, although to our knowledge whether P2Y(12) receptors are
      involved in the regulation of bone metabolism has not yet been investigated.
      Therefore, the objective of the present study was to investigate the association
      between clopidogrel use and risk of fractures. METHODS: We investigated the
      association between clopidogrel use and fracture incidence in a nationwide cohort
      study within the Danish population of approximately 5.3 million individuals. All
      patients who were prescribed clopidogrel during the years 1996-2008 were included
      in the study (n = 77 503), and three nonusers were randomly selected, matched for
      age and gender (n = 232 510), for each clopidogrel-treated subject. RESULTS:
      Treatment with clopidogrel was associated with both increased overall fracture
      risk and increased risk of osteoporotic fractures, especially in subjects with a
      treatment duration of more than 1 year. However, individuals with low exposure to
      clopidogrel (<0.01 defined daily dose) had a lower risk of fracture than never
      users. CONCLUSIONS: Use of the P2Y(12) inhibitor clopidogrel is associated with
      risk of fractures. There seems to be a biphasic relation so that lower doses are
      associated with decreased fracture risk, whereas higher doses (recommended dose
      range) are associated with increased risk. More studies are warranted to
      determine the potential in vivo effect of platelet aggregation inhibitors on bone
      metabolism.

PMID- 22372977
TI  - A quantitative analysis of monochromaticity in genetic interaction networks.
AB  - BACKGROUND: A genetic interaction refers to the deviation of phenotypes from the
      expected when perturbing two genes simultaneously. Studying genetic interactions
      help clarify relationships between genes, such as compensation and masking, and
      identify gene groups of functional modules. Recently, several genome-scale
      experiments for measuring quantitative (positive and negative) genetic
      interactions have been conducted. The results revealed that genes in the same
      module usually interact with each other in a consistent way (pure positive or
      negative); this phenomenon was designated as monochromaticity. Monochromaticity
      might be the underlying principle that can be utilized to unveil the modularity
      of cellular networks. However, no appropriate quantitative measurement for this
      phenomenon has been proposed. RESULTS: In this study, we propose the
      monochromatic index (MCI), which is able to quantitatively evaluate the
      monochromaticity of potential functional modules of genes, and the MCI was used
      to study genetic landscapes in different cellular subsystems. We demonstrated
      that MCI not only amend the deficiencies of MP-score but also properly
      incorporate the background effect. The results showed that not only within
      complex but also between-complex connections present significant monochromatic
      tendency. Furthermore, we also found that significantly higher proportion of
      protein complexes are connected by negative genetic interactions in metabolic
      network, while transcription and translation system adopts relatively even number
      of positive and negative genetic interactions to link protein complexes.
      CONCLUSION: In summary, we demonstrate that MCI improves deficiencies suffered by
      MP-score, and can be used to evaluate monochromaticity in a quantitative manner.
      In addition, it also helps to unveil features of genetic landscapes in different
      cellular subsystems. Moreover, MCI can be easily applied to data produced by
      different types of genetic interaction methodologies such as Synthetic Genetic
      Array (SGA), and epistatic miniarray profile (E-MAP).

PMID- 22372978
TI  - Correlation of cell membrane dynamics and cell motility.
AB  - BACKGROUND: Essential events of cell development and homeostasis are revealed by
      the associated changes of cell morphology and therefore have been widely used as
      a key indicator of physiological states and molecular pathways affecting various
      cellular functions via cytoskeleton. Cell motility is a complex phenomenon
      primarily driven by the actin network, which plays an important role in shaping
      the morphology of the cells. Most of the morphology based features are
      approximated from cell periphery but its dynamics have received none to scant
      attention. We aim to bridge the gap between membrane dynamics and cell states
      from the perspective of whole cell movement by identifying cell edge patterns and
      its correlation with cell dynamics. RESULTS: We present a systematic study to
      extract, classify, and compare cell dynamics in terms of cell motility and edge
      activity. Cell motility features extracted by fitting a persistent random walk
      were used to identify the initial set of cell subpopulations. We propose
      algorithms to extract edge features along the entire cell periphery such as
      protrusion and retraction velocity. These constitute a unique set of multivariate
      time-lapse edge features that are then used to profile subclasses of cell
      dynamics by unsupervised clustering. CONCLUSIONS: By comparing membrane dynamic
      patterns exhibited by each subclass of cells, correlated trends of edge and cell
      movements were identified. Our findings are consistent with published literature
      and we also identified that motility patterns are influenced by edge features
      from initial time points compared to later sampling intervals.

PMID- 22372979
TI  - Nuclease activity via self-activation and anticancer activity of a mononuclear
      copper(II) complex: novel role of the tertiary butyl group in the ligand frame.
AB  - The copper complex [Cu((t)BuPhimp)(Cl)] (1) derived from tridentate ligand
      (t)BuPhimpH having N(2)O donors was synthesized, and its molecular structure was
      determined. A phenoxyl radical complex was generated in solution at room
      temperature using Ce(IV). The nuclease and anticancer activities of 1 were
      investigated. The roles of the tert-butyl group and singlet oxygen in the DNA
      cleavage activity were also discussed.

PMID- 22372981
TI  - Mimicking of cerebral autoregulation by flow-dependent cerebrovascular
      resistance: a feasibility study.
AB  - Understanding circulatory autoregulation is essential for improving physiological
      control of rotary blood pumps and support conditions during cardiopulmonary
      bypass (CPB). Cerebral autoregulation (CAR), arguably the most critical, is the
      body's intrinsic ability to maintain sufficient cerebral blood flow (CBF) despite
      changes in aortic perfusion pressure. It is therefore imperative to include this
      mechanism into computational fluid dynamics (CFD), particle image velocimetry
      (PIV), or mock circulation loop (MCL) studies. Without such inclusions, potential
      losses of CBF are overestimated. In this study, a mathematical model to mimic CAR
      is implemented in a MCL- and PIV-validated CFD model. A three-dimensional model
      of the human vascular system was created from magnetic resonance imaging records.
      Numerical flow simulations were performed for physiological conditions and CPB.
      The inlet flow was varied between 4.5 and 6 L/min. Arterial outlets were modeled
      using vessel-specific, flow-dependent cerebrovascular resistances (CVRs),
      resulting in a variation of the pressure drop between 0 and 80mmHg. CBF is highly
      dependent on the level of CAR during CPB. By varying the CVR parameters up to the
      beginning of plateau phase, it can be regulated between 0 and 80% of
      physiological CBF. So while implementing autoregulation, CBF remains unchanged
      during a simulated native cardiac output of 5L/min or CPB support of 6L/min.
      Neglecting CAR, constant backflow from the brain occurs for some cannula
      positions. Using flow-dependent CVR, CBF returns to its baseline at a rate of
      recovery of 0.25s. Results demonstrate that modeling of CAR by flow-dependent CVR
      delivers feasible results. The presented method can be used to optimize
      physiological control of assist devices dependent upon different levels of CAR
      representing different patients.

PMID- 22372982
TI  - The recognition of facial expressions: an investigation of the influence of age
      and cognition.
AB  - The present study aimed to investigate changes in facial expression recognition
      across the lifespan, as well as to determine the influence of fluid intelligence,
      processing speed, and memory on this ability. Peak performance in the ability to
      identify facial affect was found to occur in middle-age, with the children and
      older adults performing the poorest. Specifically, older adults were impaired in
      their ability to identify fear, sadness, and happiness, but had preserved
      recognition of anger, disgust, and surprise. Analyses investigating the influence
      of cognition on emotion recognition demonstrated that cognitive abilities
      contribute to performance, especially for participants over age 45. However, the
      cognitive functions did not fully account for the older adults' impairments on
      expression recognition. Overall, the age-related deficits in facial expression
      recognition have implications for older adults' use of non-verbal communicative
      information.

PMID- 22372983
TI  - Neurologic parameters in the perinatal period in children with neurodevelopmental
      disorders.
AB  - Cerebral palsy (CP) is a term encompassing a group of nonprogressive,
      noncontagious conditions causing mild, moderate or severe disorders of
      neurodevelopment. OBJECTIVE: Objective of this study was to analyze the possible
      prenatal etiological factors for the emergence of neurodevelopmental disorders
      (NDs) and CP from the medical records of 100 children with neuromotor
      disabilities who were treated in Special Hospital for Children with Neuro
      developmental and Movement Disorders, Goljak, Croatia. RESULTS: ND and CP were
      more often diagnosed in children with birth weight below 2500 g which was
      statistically proved at the level of significance reaching 0.05, although
      significant correlation was low for both parameters reaching 0.21. There are both
      statistically significant differences and the statistically significant
      correlation between the three gestational age categories within ND and CP. There
      were more children with the birth weight below 2500 g in the CP than in the ND
      group and the difference was statistically significant. In the CP group, there
      were more children with the lower gestational age than in the ND group, which was
      statistically highly significant. This difference, together with correlation is
      significant at the level of 0.01. CONCLUSION: Further studies on the etiology of
      NDs are needed, with particular focus on the intrauterine risk factors.

PMID- 22372984
TI  - Evolving practice patterns for the management of small renal masses in the USA.
AB  - What's known on the subject? and What does the study add? Treatment options for
      small renal masses include radical nephrectomy (RN), partial nephrectomy (PN),
      ablation, and surveillance. PN provides equivalent oncological as RN for small
      tumours, but long-term outcomes for ablation and surveillance are poorly defined.
      Due to changing techniques and technology, treatment patterns for small renal
      masses are rapidly developing. Prior studies had analysed utilisation trends for
      PN and RN to 2006, revealing a relative rise in the rate of PN. However, overall
      treatment trends including surveillance and ablation had not been studied using a
      population-based cohort. It has become increasingly clear that RN is associated
      with greater renal and cardiovascular deterioration than nephron-sparing
      treatments. Thus, it is important to understand current population-based practice
      patterns for the treatment of small renal masses to assess whether practitioners
      are adhering to ever-changing principles in this field. The present study
      provides up-to-date treatment trends in the USA using a large population-based
      cohort. OBJECTIVE: To describe the changing practice patterns in the management
      of small renal masses, including the use of surveillance and ablative techniques.
      PATIENTS AND METHODS: All patients in the Surveillance, Epidemiology and End
      Results (SEER) registry treated for renal masses of <=7 cm in diameter, from 1998
      to 2008, were included for analysis. Annual trends in the use of surveillance,
      ablation, partial nephrectomy (PN), and radical nephrectomy (RN) were calculated.
      Multinomial logistic regression was used to determine the association of
      demographic and clinical characteristics with treatment method. RESULTS: In all,
      48 148 patients from 17 registry sites with a mean age of 63.4 years were
      included for analysis. Between 1998 and 2008, for masses of <2 cm and 2.1-4 cm,
      there was a dramatic increase in the proportion of patients undergoing PN (31% vs
      50%, 16% vs 33%, respectively) and ablation (1% vs 11%, 2% vs 9%, respectively).
      In multivariable analysis, later year of diagnosis, male gender, being married,
      clinically localised disease, and smaller tumours were associated with increased
      use of PN vs RN. Later year of diagnosis, male gender, being unmarried, smaller
      tumour, and the presence of bilateral masses were associated with increased use
      of ablation and surveillance vs RN. CONCLUSIONS: PN is now used in half of all
      patients with the smallest renal masses, and its use continues to increase over
      time. Ablation and surveillance are less common overall, but there is increased
      usage over time in select populations.

PMID- 22372985
TI  - Sleep, blood pressure and obesity in 22,389 New Zealanders.
AB  - AIM: To determine the relationship of sleep disorders with blood pressure and
      obesity in a large, relatively healthy, community-based cohort. METHODS: A cross
      sectional study was undertaken using data from 22,389 volunteer blood donors in
      New Zealand aged 16-84 years. Height, weight, neck circumference and blood
      pressure were measured directly, and data on sleep and other factors were
      ascertained using a validated self-administered questionnaire. RESULTS: Even in a
      relatively young, non-clinical cohort, lack of sleep (34%), snoring (33%), high
      blood pressure (20%) and obesity (19%) are common. After adjusting for relevant
      confounders, participants at high risk of sleep apnoea had double the odds of
      having high blood pressure but only in participants over 40 years. Very low and
      high quantities of sleep are also associated with high blood pressure. Even after
      controlling for neck circumference, self-reported sleep apnoea, sleep
      dissatisfaction and low amounts of sleep are associated with a higher body mass
      index. CONCLUSIONS: Obesity and hypertension have significant associations with a
      variety of sleep disorders, even in those less than 40 years of age and after
      adjusting for a wide range of potential confounders.

PMID- 22372986
TI  - The role of periprostatic and periseminal vesicle lymph node metastasis in the
      staging and prognosis of prostate cancer.

PMID- 22372987
TI  - An evaluation of scaling factors for multiparameter scaling procedures based on
      DFT force fields.
AB  - An extended database of scaling factors for calculating fundamental frequencies
      within multiparameter scaled quantum mechanical (SQM) force field, and effective
      scaling frequency factor (ESFF) methods, based on various DFT force fields is
      reported. Twenty-six density functionals have been examined in conjunction with
      various Pople's and Dunning's basis sets of VDZ and VTZ quality. The calculations
      were based on a standard training set of 30 molecules proposed by Baker et al.,
      for which 660 vibrational modes were assigned. Six functionals turned out to be
      particularly well-suited to the calculations oriented toward determination of
      scaled frequencies. They are B3LYP, B3PW91, B97, B97-1, B97-2, and O3LYP; they
      are all capable of providing reasonable scaled frequencies even for the small, 6
      31G* basis set (rms <15 cm(-1)). Correlations between the quality of the scaled
      frequencies and the basis set quality as well as the accuracy of the predicted
      molecular geometry were investigated. The 6-311+G** basis set turned out to be
      preferable. In addition, correlation between the rms values in the scaled
      frequencies and the errors in the predicted geometric parameters was found. Both
      11- and 9-parameter scaling frames are compared. It is shown that 9-parameter
      scaling is preferable in the middle range of the vibrational spectrum (500-2500
      cm(-1)), provided it was based on high-quality force fields. Finally, statistical
      uncertainties of the calculated scaling factors are reported.

PMID- 22372988
TI  - Integrative analysis workflow for the structural and functional classification of
      C-type lectins.
AB  - BACKGROUND: It is important to understand the roles of C-type lectins in the
      immune system due to their ubiquity and diverse range of functions in animal
      cells. It has been observed that currently confirmed C-type lectins share a
      highly conserved domain known as the C-type carbohydrate recognition domain
      (CRD). Using the sequence profile of the CRD, an increasing number of putative C
      type lectins have been identified. Hence, it is highly needed to develop a
      systematic framework that enables us to elucidate their carbohydrate (glycan)
      recognition function, and discover their physiological and pathological roles.
      RESULTS: Presented herein is an integrated workflow for characterizing the
      sequence and structural features of novel C-type lectins. Our workflow utilizes
      web-based queries and available software suites to annotate features that can be
      found on the C-type lectin, given its amino acid sequence. At the same time, it
      incorporates modeling and analysis of glycans - a major class of ligands that
      interact with C-type lectins. Thereafter, the results are analyzed together with
      context-specific knowledge to filter off unlikely predictions. This allows
      researchers to design their subsequent experiments to confirm the functions of
      the C-type lectins in a systematic manner. CONCLUSIONS: The efficacy and
      usefulness of our proposed immunoinformatics workflow was demonstrated by
      applying our integrated workflow to a novel C-type lectin -CLEC17A - and we
      report some of its possible functions that warrants further validation through
      wet-lab experiments.

PMID- 22372991
TI  - Preventing thiol-yne addition improves the specificity of strain-promoted azide
      alkyne cycloaddition.
AB  - The 1,3-dipolar cycloaddition of azides with ring-strained alkynes is one of the
      few bioorthogonal reactions suitable for specific biomolecule labeling in complex
      biological systems. Nevertheless, azide-independent labeling of proteins by
      strained alkynes can occur to a varying extent, thereby limiting the sensitivity
      of assays based on strain-promoted azide-alkyne cycloaddition (SPAAC). In this
      study, a subset of three cyclooctynes, dibenzocyclooctyne (DIBO),
      azadibenzocyclooctyne (DIBAC), and bicyclo[6.1.0]nonyne (BCN), was used to
      evaluate the azide-independent labeling of proteins in vitro. For all three
      cyclooctynes, we show that thiol-yne addition with reduced peptidylcysteines is
      responsible for most of the azide-independent polypeptide labeling. The identity
      of the reaction product was confirmed by LC-MS and NMR analysis. Moreover, we
      show that undesired thiol-yne reactions can be prevented by alkylating
      peptidylcysteine thiols with iodoacetamide (IAM). Since IAM is compatible with
      SPAAC, a more specific azide-dependent labeling is achieved by preincubating
      proteins containing reduced cysteines with IAM.

PMID- 22372993
TI  - The south-east Scotland dermatology workload study: 30 years' analysis.
AB  - BACKGROUND: Dermatological activity data have been collected for the same region
      of south-east Scotland (population 1.24 million), approximately every 5 years,
      since 1981. This has allowed assessment of trends in demand from primary and
      secondary care, and activity within secondary care dermatology services,
      assisting planning of dermatological services. OBJECTIVES: To quantify
      dermatology outpatient workload across the same population to allow comparison
      with previous studies for trends in practice. METHODS: During November 2010, a
      standardized proforma was completed for all National Health Service and private
      practice dermatology outpatient consultations. Demographic data, source and
      reason for referral, diagnoses, investigations, treatments and disposal were
      recorded, and comparisons made with five previous studies. RESULTS: A total of
      5470 consultations were recorded: 2882 new and 2588 review patients (new to
      review ratio 1 : 0.9, male to female 1 : 1.3, mean age 49 years, range 1 month to
      101 years). Ninety-one per cent of referrals came from primary care and 9% from
      secondary care. Fifty-eight per cent of referrals were for diagnosis and 32% for
      hospital management. Diagnostic concordance between referrer and dermatologist
      ranged from 94% for acne to 14% for melanoma. Benign tumours accounted for 30% of
      referrals, malignant tumours 13%, dermatitis 13.3%, psoriasis 6.2% and
      acne/rosacea 5%. The referral rate rose to 23.2/1000 population per annum, with
      the increase coming mainly from primary care. CONCLUSIONS: Demand for dermatology
      continues to increase: new referrals have risen by 134% in 30 years, with a 36%
      increase in the last 5 years, despite corresponding population increases of 5.3%
      and 3%, respectively.

PMID- 22372994
TI  - Family history of venous thromboembolism is associated with increased risk for
      thrombosis in multiple myeloma: a population-based study.

PMID- 22372995
TI  - Looking for the physiological role of anthocyanins in the leaves of Coffea
      arabica.
AB  - The aim of this study was to determine which anthocyanins are related to the
      purple coloration of young leaves in Coffea arabica var. Purpurascens and assess
      their impact on photosynthesis as compared to C. arabica var. Catuai, with green
      leaves. Two delphinidin glicosides were identified and histological cross
      sections showed they were located throughout the adaxial epidermis in young
      leaves, disappearing as the leaves mature. Regardless the irradiance level, the
      photosynthetic performance of Purpurascens leaves did not differ from that
      observed in leaves of the Catuai variety, providing no evidence that anthocyanins
      improve photosynthetic performance in coffee plants. To analyze the
      photoprotective action of anthocyanins, we evaluated the isomerization process
      for chlorogenic acids (CGAs) in coffee leaves exposed to UV-B radiation. No
      differences were observed in the total concentration of phenolic compounds in
      either variety before or after the UV treatment; however, we observed less
      degradation of CGA isomers in the Purpurascens leaves and a relative increase of
      cis-5-caffeoylquinic acid, a positional isomer of one of the most abundant form
      of CQA in coffee leaves, trans-5-caffeoylquinic acid, suggesting a possible
      protective role for anthocyanins in this purple coffee variety.

PMID- 22372996
TI  - Surface-engineered gold nanorods: promising DNA vaccine adjuvant for HIV-1
      treatment.
AB  - With the intense international response to the AIDS pandemic, HIV vaccines have
      been extensively investigated but have failed due to issues of safety or efficacy
      in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a
      rational design approach is still lacking. Nanomaterials represent an obvious
      opportunity in this field due to their unique physicochemical properties. Gold
      nanostructures are being actively studied as a promising and versatile platform
      for biomedical application. Herein, we report novel surface-engineered gold
      nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have
      exploited the effects of surface chemistry on the adjuvant activity of the gold
      nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium
      bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and
      polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI
      modified Au NRs can significantly promote cellular and humoral immunity as well
      as T cell proliferation through activating antigen-presenting cells if compared
      to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light
      on the rational design of low-toxic nanomaterials as a versatile platform for
      vaccine nanoadjuvants/delivery systems.

PMID- 22372998
TI  - Can persistent organic pollutants and plastic-associated chemicals cause
      cardiovascular disease?
AB  - During the last decade, associations between persistent organic pollutants
      (POPs), such as polychlorinated biphenyls, dioxins and pesticides, and
      cardiovascular (CV) risk factors and overt CV disease (CVD) have been reported in
      humans. Recently, associations between plastic-associated chemicals (PACs), such
      as bisphenol A and phthalates, and CVD have also begun to emerge. Several
      approaches to evaluating such associations have been used: accidents with a high
      level of exposure, occupational exposure studies, geographical studies of
      subjects living near a contaminated area and traditional case-control or cohort
      studies with measurements of circulating levels of different environmental
      contaminants in the general population. Exposure to POPs has consistently been
      associated with diabetes using all the approaches described above, including
      prospective studies. The evidence regarding associations between exposure to POPs
      and other CV risk factors, such as hypertension, obesity and lipids, is less
      strong and is mainly based on cross-sectional data. Associations between overt
      CVD and POPs have been reported using all the above approaches, but prospective
      data from population-based studies are still lacking to provide firm evidence of
      an important and independent role of POP exposure in the pathogenesis of CVD.
      Nevertheless, taken together, current evidence suggests that further longitudinal
      and experimental studies should be conducted to investigate the effect of
      exposure to both POPs and PACs, such as bisphenol A and phthalates.

PMID- 22372999
TI  - Argudas: lessons for argumentation in biology based on a gene expression use
      case.
AB  - BACKGROUND: In situ hybridisation gene expression information helps biologists
      identify where a gene is expressed. However, the databases that republish the
      experimental information online are often both incomplete and inconsistent. Non
      monotonic reasoning can help resolve such difficulties - one such form of
      reasoning is computational argumentation. Essentially this involves asking a
      computer to debate (i.e. reason about) the validity of a particular statement.
      Arguments are produced for both sides - the statement is true and, the statement
      is false - then the most powerful argument is used. In this work the computer is
      asked to debate whether or not a gene is expressed in a particular mouse
      anatomical structure. The information generated during the debate can be passed
      to the biological end-user, enabling their own decision-making process. RESULTS:
      This paper examines the evolution of a system, Argudas, which tests using
      computational argumentation in an in situ gene hybridisation gene expression use
      case. Argudas reasons using information extracted from several different online
      resources that publish gene expression information for the mouse. The development
      and evaluation of two prototypes is discussed. Throughout a number of issues
      shall be raised including the appropriateness of computational argumentation in
      biology and the challenges faced when integrating apparently similar online
      biological databases. CONCLUSIONS: From the work described in this paper it is
      clear that for argumentation to be effective in the biological domain the
      argumentation community need to develop further the tools and resources they
      provide. Additionally, the biological community must tackle the incongruity
      between overlapping and adjacent resources, thus facilitating the integration and
      modelling of biological information. Finally, this work highlights both the
      importance of, and difficulty in creating, a good model of the domain.

PMID- 22373000
TI  - Deep venous thrombosis and pulmonary embolism secondary to co-administration of
      thalidomide and oral corticosteroid in a patient with leprosy.
AB  - A 58-year-old Japanese man with a 2-year history of multidrug therapy for
      borderline lepromatous leprosy presented with skin lesions suggestive of erythema
      nodosum leprosum (ENL) and was treated with an oral corticosteroid. As attempts
      to taper the oral corticosteroid resulted in the appearance of new lesions,
      thalidomide was added along with cyclosporin. Two months after the introduction
      of thalidomide, deep venous thrombosis (DVT) occurred in both legs and
      anticoagulant therapy was started without cessation of thalidomide. Pulmonary
      embolism developed 1 month after the appearance of DVT, and these thromboembolic
      events were believed to be due to thalidomide. This case highlights the need for
      vigilance against venous thromboembolism when corticosteroid and thalidomide are
      co-administrated for the treatment of ENL.

PMID- 22373002
TI  - Effect of self-administered auricular acupressure on smoking cessation--a pilot
      study.
AB  - BACKGROUND: Tobacco smoking is still a worldwide health risk. Current
      pharmacotherapies have at best, a success rate of no more than 50%. Auricular
      (ear) acupressure has been purported to be beneficial in achieving smoking
      cessation in some studies, while in others has been deemed insignificant. We
      hereby describe the protocol for a three-arm randomised controlled trial to
      examine the possible benefits of self-administered acupressure for smoking
      cessation. METHODS: Sixty consenting participants with confirmed habit of tobacco
      smoking will be recruited and randomized into three arms to receive either
      auricular acupressure at five true acupoints (NADA protocol), auricular
      acupressure at five sham points, or no auricular acupressure at all. Participants
      having auricular acupressure will exert firm pressure to each acupoint
      bilaterally via the bead in the attached plasters whenever they feel the urge to
      smoke. The treatment phase will last for six weeks during which all participants
      will be assessed weekly to review their smoking log, state of abstinence, end
      exhalation carbon monoxide levels and possible adverse effects including
      withdrawal reactions and stress levels. At any time, a successful quit date will
      be defined with continuous abstinence for the following consecutive 7 days. From
      then on, participants will be evaluated individually for continuous abstinence
      rate (CAR), end-exhalation carbon monoxide levels and adverse effects of stress
      and withdrawal at specified intervals up to 26 weeks. Expectancy of treatment
      will be assessed with a four-item Borkovec and Nau self-assessment credibility
      scale during and after intervention. DISCUSSION: We incorporate validated outcome
      measures of smoking cessation into our randomised controlled trial design with
      the objectives to evaluate the feasibility and possible benefits of self
      administered auricular acupressure as a non-invasive alternative to
      pharmacotherapy for smoking cessation. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01389622 (registered Jul 7 2011).

PMID- 22373004
TI  - Stability of building gene regulatory networks with sparse autoregressive models.
AB  - BACKGROUND: Biological networks are constantly subjected to random perturbations,
      and efficient feedback and compensatory mechanisms exist to maintain their
      stability. There is an increased interest in building gene regulatory networks
      (GRNs) from temporal gene expression data because of their numerous applications
      in life sciences. However, because of the limited number of time points at which
      gene expressions can be gathered in practice, computational techniques of
      building GRN often lead to inaccuracies and instabilities. This paper
      investigates the stability of sparse auto-regressive models of building GRN from
      gene expression data. RESULTS: Criteria for evaluating the stability of
      estimating GRN structure are proposed. Thereby, stability of multivariate vector
      autoregressive (MVAR) methods - ridge, lasso, and elastic-net - of building GRN
      were studied by simulating temporal gene expression datasets on scale-free
      topologies as well as on real data gathered over Hela cell-cycle. Effects of the
      number of time points on the stability of constructing GRN are investigated. When
      the number of time points are relatively low compared to the size of network,
      both accuracy and stability are adversely affected. At least, the number of time
      points equal to the number of genes in the network are needed to achieve decent
      accuracy and stability of the networks. Our results on synthetic data indicate
      that the stability of lasso and elastic-net MVAR methods are comparable, and
      their accuracies are much higher than the ridge MVAR. As the size of the network
      grows, the number of time points required to achieve acceptable accuracy and
      stability are much less relative to the number of genes in the network. The
      effects of false negatives are easier to improve by increasing the number time
      points than those due to false positives. Application to HeLa cell-cycle gene
      expression dataset shows that biologically stable GRN can be obtained by
      introducing perturbations to the data. CONCLUSIONS: Accuracy and stability of
      building GRN are crucial for investigation of gene regulations. Sparse MVAR
      techniques such as lasso and elastic-net provide accurate and stable methods for
      building even GRN of small size. The effect of false negatives is corrected much
      easier with the increased number of time points than those due to false
      positives. With real data, we demonstrate how stable networks can be derived by
      introducing random perturbation to data.

PMID- 22373005
TI  - Growth and death kinetics of CHO cells cultivated in continuous bioreactor at
      various agitation rates.

PMID- 22373006
TI  - The systemic effect of 830-nm LED phototherapy on the wound healing of burn
      injuries: A controlled study in mouse and rat models.
AB  - BACKGROUND: The present controlled study assessed the systemic effect of 830-nm
      LED phototherapy in rodent models. MATERIALS AND METHODS: Two HR-1 hairless mice
      and 3 HWY/Slc hairless rats were divided into two groups: the treatment group (Tx
      Group, one mouse, two rats) and the control group (Con Group, one mouse, one
      rat). All animals received an identical 12 mm * 12 mm control burn over three
      sites on the dorsum with a fractional ablative CO(2) laser. Wounds were protected
      with a film-type dressing. The abdomen of the Tx Group subjects was irradiated
      with an 830-nm LED array immediately post CO(2) treatment and then at 1, 5 and 6
      days post laser irradiation. Wound healing was assessed macroscopically from the
      clinical photography. RESULTS: At the 2-day post-laser assessment, the healing
      process in the wounds in the Tx Group was already apparent compared with the Con
      Group. At the final evaluation (post-burn day 7), no site on the Con Group (six
      wounds) showed 100% healing, recovery was over 70% in four and lower than 50% in
      two sites. Of the nine Tx Group sites, 100% recovery was seen in three sites,
      over 70% in five sites and one wound was exacerbated through trauma. CONCLUSIONS:
      LED phototherapy on the abdomen produced faster wound healing of the uniform burn
      wounds than in animals with the same burn wounds that did not receive LED
      phototherapy, strongly suggesting the systemic effect of phototherapy.

PMID- 22373008
TI  - Properties of N(4)-methylated cytidines in miRNA mimics.
AB  - Experiments conducted with micro RNA (miRNA) mimics often result in subtle
      phenotypic changes and hence require careful controls. A commonly used type of
      control reagent in the antisense/RNA interference fields is the mismatched
      sequence. However, it is difficult to use mismatch controls for miRNAs, mainly
      because base permutation in the seed region may generate a new miRNA seed with
      its own associated target transcripts. We incorporated N(4)-methylcytidine and
      N(4),N(4)-dimethylcytidine into a series of RNAs using the convertible nucleoside
      approach and measured their effects on hybridization affinity with complementary
      RNAs, and on miRNA-mediated and small interfering RNA (SiRNA)-mediated silencing.
      We report here that incorporation of a single N(4),N(4)-dimethylcytidine into the
      seed region of miRNAs can be used as a new class of negative miRNA control which
      (1) does not constitute a new seed sequence; (2) is accepted by the RNA-induced
      silencing complex (RISC); (3) causes a significant loss of binding affinity to
      target RNAs; and (4) is synthesized conveniently into oligoribonucleotides.

PMID- 22373003
TI  - Nijmegen breakage syndrome (NBS).
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of
      chromosomal instability mainly characterized by microcephaly at birth, combined
      immunodeficiency and predisposition to malignancies. Due to a founder mutation in
      the underlying NBN gene (c.657_661del5) the disease is encountered most
      frequently among Slavic populations. The principal clinical manifestations of the
      syndrome are: microcephaly, present at birth and progressive with age, dysmorphic
      facial features, mild growth retardation, mild-to-moderate intellectual
      disability, and, in females, hypergonadotropic hypogonadism. Combined cellular
      and humoral immunodeficiency with recurrent sinopulmonary infections, a strong
      predisposition to develop malignancies (predominantly of lymphoid origin) and
      radiosensitivity are other integral manifestations of the syndrome. The NBN gene
      codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear
      role wherever double-stranded DNA ends occur, either physiologically or as a
      result of mutagenic exposure. Laboratory findings include: (1) spontaneous
      chromosomal breakage in peripheral T lymphocytes with rearrangements
      preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing
      radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by
      colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic
      hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin
      protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency
      (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth
      retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1
      syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4
      syndrome. Genetic counselling should inform parents of an affected child of the
      25% risk for further children to be affected. Prenatal molecular genetic
      diagnosis is possible if disease-causing mutations in both alleles of the NBN
      gene are known. No specific therapy is available for NBS, however, hematopoietic
      stem cell transplantation may be one option for some patients. Prognosis is
      generally poor due to the extremely high rate of malignancies.

PMID- 22373009
TI  - Monotherapy for comorbid erectile dysfunction and lower urinary tract symptoms:
      phosphodiesterase inhibitor or alpha-adrenoceptor antagonist?

PMID- 22373010
TI  - Internal affairs: investigating the Brucella intracellular lifestyle.
AB  - Bacteria of the genus Brucella are Gram-negative pathogens of several animal
      species that cause a zoonotic disease in humans known as brucellosis or Malta
      fever. Within their hosts, brucellae reside within different cell types where
      they establish a replicative niche and remain protected from the immune response.
      The aim of this article is to discuss recent advances in the field in the
      specific context of the Brucella intracellular 'lifestyle'. We initially discuss
      the different host cell targets and their relevance during infection. As it
      represents the key to intracellular replication, the focus is then set on the
      maturation of the Brucella phagosome, with particular emphasis on the Brucella
      factors that are directly implicated in intracellular trafficking and modulation
      of host cell signalling pathways. Recent data on the role of the type IV
      secretion system are discussed, novel effector molecules identified and how some
      of them impact on trafficking events. Current knowledge on Brucella gene
      regulation and control of host cell death are summarized, as they directly affect
      intracellular persistence. Understanding how Brucella molecules interplay with
      their host cell targets to modulate cellular functions and establish the
      intracellular niche will help unravel how this pathogen causes disease.

PMID- 22373011
TI  - The way to a design space for an animal cell culture process according to Quality
      by Design (QbD).

PMID- 22373012
TI  - Periprostatic lymph node metastasis in prostate cancer and its clinical
      significance.
AB  - AIMS: To evaluate the potential of periprostatic lymph node (LN) as a staging
      indicator, particularly with the use of methods for enhanced detection of
      micrometastasis. METHODS AND RESULTS: We retrieved cases with periprostatic LN
      from radical prostatectomy specimens accrued between 1997 and 2007 at our
      institution. Twenty-one (0.8%) of 2663 radical prostatectomy specimens had
      periprostatic LNs (total number of LNs = 22). LN size ranged from 0.8 to 4.7 mm.
      Most of the periprostatic LNs were located close to the posterior base. Seven
      (32%) of 22 LNs were involved by metastatic prostate cancer (PCa), including five
      detected on routine haematoxylin and ceosin slides and an additional two detected
      only by immunohistochemistry. Cases with periprostatic LNs had a significantly
      higher metastatic rate (29%; six of 21) compared to those with pelvic LNs sampled
      at radical prostectatomy in our institution (1.9%). When compared to cases with
      negative periprostatic LNs (n = 15), the tumour characteristics of cases with
      metastatic periprostatic LNs (n = 6) included higher tumour volume, Gleason
      score, stage and a greater propensity for prostate-specific antigen (PSA)
      recurrence. CONCLUSIONS: Despite their infrequent identification, periprostatic
      LNs if detected in the radical prostatectomy specimen should be evaluated with
      greater scrutiny (step sections and/or immunohistochemical studies) to evaluate
      their prognostic potential.

PMID- 22373013
TI  - Novel base triples in RNA structures revealed by graph theoretical searching
      methods.
AB  - BACKGROUND: Highly hydrogen bonded base interactions play a major part in
      stabilizing the tertiary structures of complex RNA molecules, such as transfer
      RNAs, ribozymes and ribosomal RNAs. RESULTS: We describe the graph theoretical
      identification and searching of highly hydrogen bonded base triples, where each
      base is involved in at least two hydrogen bonds with the other bases. Our
      approach correlates theoretically predicted base triples with literature-based
      compilations and other actual occurrences in crystal structures. The use of
      'fuzzy' search tolerances has enabled us to discover a number of triple
      interaction types that have not been previously recorded nor predicted
      theoretically. CONCLUSIONS: Comparative analyses of different ribosomal RNA
      structures reveal several conserved base triple motifs in 50S rRNA structures,
      indicating an important role in structural stabilization and ultimately RNA
      function.

PMID- 22373014
TI  - Method for identifying eligible individuals for a prevalence survey in the
      absence of a disease register or population register.
AB  - BACKGROUND: Identifying eligible individuals for a prevalence survey is difficult
      in the absence of a disease register or a national population register. AIM: To
      develop a method to identify and invite eligible individuals to participate in a
      national prevalence survey while maintaining confidentiality and complying with
      privacy legislation. METHODS: A unique identifier (based on date of birth, sex
      and initials) was developed so that database holders could identify eligible
      individuals, notify us and invite them on our behalf to participate in a national
      multiple sclerosis prevalence survey while maintaining confidentiality and
      complying with privacy legislation. RESULTS: Several organisations (including
      central government, health and non-governmental organisations) used the method
      described to assign unique identifiers to individuals listed on their databases
      and to forward invitations and consent forms to them. The use of a unique
      identifier allowed us to recognise and record all the sources of identification
      for each individual. This prevented double counting or approaching the same
      individual more than once and facilitated the use of capture-recapture methods to
      improve the prevalence estimate. Capture-recapture analysis estimated that the
      method identified over 96% of eligible individuals in this prevalence survey.
      CONCLUSIONS: This method was developed and used successfully in a national
      prevalence survey of multiple sclerosis in New Zealand. The method may be useful
      for prevalence surveys of other diseases in New Zealand and for prevalence
      surveys in other countries with similar privacy legislation and lack of disease
      registers and population registers.

PMID- 22373015
TI  - Towards human central nervous system in vitro models for preclinical research:
      strategies for 3D neural cell culture.

PMID- 22373016
TI  - A new concept of a multidisciplinary lymphoedema centre: established in
      connection to a department of dermatology and the Copenhagen Wound Healing
      Center.
AB  - BACKGROUND: Lymphoedema is increasingly recognized as a significant problem in
      healthcare. The number of patients is growing, posing a future challenge to
      healthcare systems and economics. Over the past decade, specialized lymphoedema
      management has been established around the world to accommodate the growing
      demands. However, information on organization, experiences and outcome are
      scarce. OBJECTIVES: To conduct a clinical perspective analysis describing the
      establishment, organization, function and results of a new, multidisciplinary
      lymphoedema centre functioning as a university hospital unit in connection to a
      department of dermatology and the Copenhagen Wound Healing Center and integrated
      as a national expert function in the public healthcare organization of Denmark.
      METHODS: Data were collected following the establishment of a lymphoedema centre
      based on the structured, multidisciplinary organization of lymphoedema
      management. RESULTS: During the first 4.5 years a total of 8058 patient
      consultations were performed. The mean duration of symptoms at the first visit
      was 19 years (range 1-67) and 31% of patients had never received any diagnosis or
      treatment prior to referral. Complications were found in 48% of referred
      patients. All patients received appropriate diagnostic investigations and
      treatment according to best practice. Multidisciplinary assessment involving four
      or more different healthcare professions was needed in 86% of cases. Research
      opportunities and expert education of staff were enhanced. CONCLUSIONS: A
      multidisciplinary lymphoedema centre improves management, knowledge and awareness
      of lymphoedema. This model, with minor adjustments, may be applicable for other
      regions and countries.

PMID- 22373018
TI  - Influence of glutamine on transient and stable recombinant protein production in
      CHO and HEK-293 cells.

PMID- 22373022
TI  - iGepros: an integrated gene and protein annotation server for biological nature
      exploration.
AB  - BACKGROUND: In the post-genomic era, transcriptomics and proteomics provide
      important information to understand the genomes. With fast development of high
      throughput technology, more and more transcriptomics and proteomics data are
      generated at an unprecedented rate. Therefore, requirement of software to
      annotate those omics data and explore their biological nature arises. In the past
      decade, some pioneer works were presented to address this issue, but limitations
      still exist. Fox example, some of these tools offer command line only, which is
      not suitable for those users with little or no experience in programming.
      Besides, some tools don't support large scale gene and protein analysis. RESULTS:
      To overcome these limitations, an integrated gene and protein annotation server
      named iGepros has been developed. The server provides user-friendly interfaces
      and detailed on-line examples, so most researchers even those with little or no
      programming experience can use it smoothly. Moreover, the server provides many
      functionalities to compare transcriptomics and proteomics data. Especially, the
      server is constructed under a model-view-control framework, which makes it easy
      to incorporate more functions to the server in the future. CONCLUSIONS: In this
      paper, we present a server with powerful capability not only for gene and protein
      functional annotation, but also for transcriptomics and proteomics data
      comparison. Researchers can survey biological characters behind gene and protein
      datasets and accelerate their investigation of transcriptome and proteome by
      applying the server. The server is publicly available at
      http://www.biosino.org/iGepros/.

PMID- 22373023
TI  - Impact on product quality of high productive GS-CHO cell lines.

PMID- 22373024
TI  - Insect cell lines and baculoviruses as effective biocontrol agents of forest
      pests.

PMID- 22373025
TI  - Assessing the impact of missing genotype data in rare variant association
      analysis.
AB  - Human genome resequencing technologies are becoming ever more affordable and
      provide a valuable source of data about rare genetic variants in the human
      genome. Such rare variation may play an important role in explaining the missing
      heritability of complex human traits. We implement an existing method for
      analyzing rare variants by testing for association with the mutational load
      across genes. In this study, we make use of simulated data from the Genetic
      Analysis Workshop 17 to assess the power of this approach to detect association
      with simulated quantitative and dichotomous phenotypes and to evaluate the impact
      of missing genotypes on the power of the analysis. According to our results, the
      mutational load based rare variant analysis method is relatively robust to call
      rate and is adequately powered for genome-wide association analysis.

PMID- 22373026
TI  - Relation of LAT1/4F2hc expression with pathological grade, proliferation and
      angiogenesis in human gliomas.
AB  - BACKGROUND: LAT1/4F2hc heterodimeric complex is a major route for the transport
      of large neutral essential amino acids through the plasma membrane. Although it
      has been shown that LAT1/4F2hc is highly expressed in a variety of human tumors
      including gliomas, and LAT1 over-expression is associated with glioma grade and
      poor prognosis of glioma patients, the precise tissue location of LAT1/4F2hc in
      gliomas and the precise role of LAT1/4F2hc in glioma biological features remain
      unclear. METHODS: In the current study, the expressions of LAT1, 4F2hc, CD34 and
      Ki-67 were investigated by immunohistochemistry in 62 cases of human brain
      glioma; LAT1/4F2hc expression level, Ki-67 labeling index (Ki-67 LI) and
      microvessel density (MVD) were measured semi-quantitatively; and the correlation
      of LAT1/4F2hc expression with histopathological features, Ki-67 LI and MVD in
      gliomas was further analyzed. RESULTS: The results showed that both LAT1 and
      4F2hc were expressed in all examined specimens. LAT1 but 4F2hc expression levels
      significantly correlated with the pathological grade and both expression levels
      significantly correlated with Ki-67 LI of gliomas. We also demonstrated that both
      LAT1 and 4F2hc immunoreactivity were observed in tumor cells as well as vascular
      endothelia; furthermore, the LAT1 expression level was markedly associated with
      glioma MVD as well. CONCLUSION: LAT1/4F2hc over-expression is closely correlates
      with the malignant phenotype and proliferation of gliomas, and LAT1 was
      associates with glioma angiogenesis. LAT1/4F2hc, especially LAT1, may become a
      novel potential molecular target for glioma biological therapy.

PMID- 22373027
TI  - Increasing antibody yield and modulating final product quality using the
      Freedom(TM) CHO-S(TM) production platform.

PMID- 22373029
TI  - Stromal opacity after cross-linking.

PMID- 22373030
TI  - Association of corneal indices for the detection of ectasia-susceptible corneas.

PMID- 22373031
TI  - Combining zonal refractive and diffractive aspheric multifocal intraocular
      lenses.
AB  - PURPOSE: To assess visual performance with the combination of a zonal refractive
      aspheric multifocal intraocular lens (MIOL) (Lentis Mplus, Oculentis GmbH) and a
      diffractive aspheric MIOL (Acri.Lisa 366, Acri.Tech GmbH). METHODS: This
      prospective interventional cohort study comprised 80 eyes from 40 cataract
      patients (mean age: 65.5+/-7.3 years) who underwent implantation of the Lentis
      Mplus MIOL in one eye and Acri.Lisa 366 MIOL in the fellow eye. The main outcome
      measures were refraction; monocular and binocular uncorrected and corrected
      distance, intermediate, and near visual acuities; monocular and binocular defocus
      curves; binocular photopic contrast sensitivity function compared to a monofocal
      intraocular lens (IOL) control group (40 age-matched pseudophakic patients
      implanted with the AR-40e [Abbott Medical Optics]); and quality of vision
      questionnaire. RESULTS: Binocular uncorrected visual acuities were 0.12 logMAR
      (0.76 decimal) or better at all distances measured between 6 m and 33 cm. The
      Lentis Mplus provided statistically significant better vision than the Acri.Lisa
      at distances between 2 m and 40 cm, and the Acri.Lisa provided statistically
      significant better vision than the Lentis Mplus at 33 cm. Binocular defocus curve
      showed little drop-off at intermediate distances. Photopic contrast sensitivity
      function for distance and near were similar to the monofocal IOL control group
      except for higher frequencies. Moderate glare (15%), night vision problems
      (12.5%), and halos (10%) were reported. Complete independence of spectacles was
      achieved by 92.5% of patients. CONCLUSIONS: The combination of zonal refractive
      aspheric and diffractive aspheric MIOLs resulted in excellent uncorrected
      binocular distance, intermediate, and near vision, with low incidence of
      significant photic phenomena and high patient satisfaction.

PMID- 22373032
TI  - Intrastromal femtosecond laser presbyopia correction: 1-year results of a
      multicenter study.
AB  - PURPOSE: To investigate functional outcomes of the INTRACOR femtosecond laser
      based intrastromal procedure to treat presbyopia. METHODS: Sixty-three eyes from
      63 presbyopic patients (median age: 54 years) with mild hyperopia were enrolled
      in this prospective, ethics committee-approved, multi-center, nonrandomized
      clinical trial. The INTRACOR procedure was performed using the Technolas
      femtosecond laser (Technolas Perfect Vision GmbH) in the nondominant eye.
      Postoperatively, follow-up was performed at 1 day, 1 week, and 1, 3, 6, and 12
      months and included near and distance visual acuity tests, slit-lamp
      examinations, and corneal topography. RESULTS: All 63 surgeries were uneventful.
      Twelve months postoperatively, outcomes of 58 (92.1%) eyes were available for
      evaluation. Median uncorrected distance visual acuity (0.1 logMAR [range: 0.5 to
      0.0 preoperatively and 0.5 to -0.1 postoperatively]) and corrected distance
      visual acuity (CDVA) (0.0 logMAR [range: 0.2 to -0.2 preoperatively and 0.3 to 
      0.1 postoperatively]) remained stable. Median spherical equivalent changed from
      +0.63 diopters (D) preoperatively to 0.00 D postoperatively. Median uncorrected
      near visual acuity increased significantly from 0.7 logMAR (range: 1.0 to 0.2)
      preoperatively to 0.2 logMAR (range: 0.8 to -0.1) postoperatively and eyes gained
      a median of 4 lines (range: 1 to 9 lines). Losses of 2 lines of CDVA were noted
      in 7.1% of eyes. Ring cuts were faintly visible at 12 months. CONCLUSIONS: The
      INTRACOR presbyopia procedure showed good and stable visual acuity outcomes over
      12-month follow-up but loss of CDVA occurred in 7% of eyes. Overall patient
      satisfaction with the procedure was approximately 80%. Short treatment time and
      maintained corneal surface integrity are advantages of this procedure.

PMID- 22373033
TI  - Comparison of the Ziemer FEMTO LDV femtosecond laser and Moria M2 mechanical
      microkeratome.
AB  - PURPOSE: To assess and compare the dimensions of LASIK flaps created by the
      Ziemer FEMTO LDV "Classic" femtosecond (FS) laser and Moria M2 microkeratome with
      110-MUm head and -20 blade. METHODS: Seven hundred twenty eyes from 360
      consecutive patients were enrolled in this study and divided into two groups of
      equal size for flap creation with the Ziemer LDV (FS laser group) and Moria M2
      mechanical microkeratome (microkeratome group). Nominal flap thickness was 110
      MUm for all patients and for both devices. Flap thickness was measured by Fourier
      domain optical coherence tomography in 14 specified positions on each flap 1 week
      after surgery to analyze the regularity, uniformity, and accuracy of the two
      types of LASIK flaps. RESULTS: The mean deviation between achieved and attempted
      flap thickness was smaller in the FS laser group than in the microkeratome group.
      The flaps in the FS laser group were more regular and uniform, showing an almost
      planar configuration, whereas flaps in the microkeratome group had a meniscus
      shape and were significantly thicker near the flap edge. Nasal and temporal flap
      thickness did not differ significantly in the FS laser group, whereas in the
      microkeratome group, characteristic differences in temporal versus nasal flap
      thickness were noticed. Within the 5040 individual measurements of the 360 eyes,
      deviations of >20 MUm were observed in 0.73% of eyes in the FS laser group and
      42.4% in the microkeratome group. CONCLUSIONS: The dimensions of flaps created by
      the Ziemer LDV femtosecond laser were more uniform and accurate than those
      created by the Moria M2 microkeratome.

PMID- 22373034
TI  - Irregularity of the posterior corneal surface during applanation using a curved
      femtosecond laser interface and microkeratome cutting head.
AB  - PURPOSE: To evaluate the irregularity of the posterior corneal surface and
      intrastromal dissection during the preparation of donor tissue for Descemet
      stripping automated endothelial keratoplasty (DSAEK) using a curved interface
      femtosecond laser and microkeratome. METHODS: Sixteen human donor corneas
      unsuitable for transplantation were divided into two groups: a femtosecond (FS)
      laser group (n=7) using the VisuMax femtosecond laser (Carl Zeiss Meditec) and a
      microkeratome group (n=9) using the Amadeus II microkeratome (Ziemer Ophthalmic
      Group). The corneas were fixed on artificial anterior chambers. Horizontal cross
      sections were obtained using spectral-domain optical coherence tomography prior
      to applanation, during applanation, as well as during and after intrastromal
      dissection at 450-MUm corneal depth. The posterior surface and the dissection
      line were evaluated for irregularity by fitting a second-order polynomial curve
      using regression analysis and obtaining the root-mean-square error (RMSE). Groups
      were compared using analysis of variance. RESULTS: The RMSE of the posterior
      surface prior to applanation was 9.7 +/- 3.1 MUm in the FS laser group and 10.2
      +/- 2.3 MUm in the microkeratome group. The RMSE increased to 50.7 +/- 9.4 MUm
      and 20.9 +/- 6.1 MUm during applanation and decreased again to 10.6 +/- 1.4 MUm
      and 8.1 +/- 1.8 MUm after applanation in the FS laser and microkeratome groups,
      respectively. The RMSE of the intrastromal cut was 19.5 +/- 5.7 MUm in the FS
      laser group and 7.7 +/- 3.0 MUm in the microkeratome group (P<.001). CONCLUSIONS:
      Our results show significantly greater irregularity with the curved interface
      femtosecond laser-assisted cleavage compared to microkeratome-assisted corneal
      dissection, possibly due to applanation-derived deformation of the posterior
      cornea.

PMID- 22373035
TI  - Wavefront ablation profiles in refractive surgery: description, results, and
      limitations.
AB  - PURPOSE: To provide an overview of the clinical results of different ablation
      profiles based on wavefront technology and discuss their characteristics and
      limitations. METHODS: Literature review of studies reporting results of ablation
      profiles based on wavefront technology in virgin healthy eyes. RESULTS: Over the
      past 10 years, a large number of studies comparing different treatment algorithms
      and newer excimer laser platforms have been published. Thirty-six clinical
      studies including 3637 eyes analyzing the clinical results obtained after
      wavefront-guided, wavefront-optimized, and Q-factor profiles have been reviewed.
      Although wavefront-driven profiles allowed reduction of the amount of induced
      optical aberrations with conventional ablations, thereby improving the quality of
      vision, it appears that no algorithm of treatment or excimer laser platform has
      demonstrated a clear superiority over another. Wound healing and unexpected
      biomechanical response to surgery affect the accuracy of customized treatments
      and produce variable results. In addition, it is difficult to rigorously analyze
      and compare findings among different studies because of the diverse variety in
      which the data are reported. CONCLUSIONS: Despite several technological
      improvements over the years, wavefront ablation profiles have not consistently
      demonstrated superiority in terms of visual acuity and lower order aberrations
      compared to the standard procedure, although the induction of higher order
      aberrations has been reduced. The concept of an individualized eye model has
      emerged recently, based on the optical ray tracing algorithm, and could
      theoretically provide a higher level of customization, thus fulfilling the
      promise of "super vision."

PMID- 22373036
TI  - Oculofacial contour asymmetries: Management of combined treatment with
      hyalurostructure and botulinum toxin injections.
AB  - PURPOSE: To assess the long-term results of the treatment of oculofacial
      asymmetries using a combined injection schedule for injections of hyaluronic
      acid, with a specific micro cannula and botulinum toxin. METHOD: A retrospective
      study was conducted from January 2009 to January 2010. Patients were treated in
      the Alcazar Eye Clinic and Oculoplastic Department in Princess Grace Hospital,
      Monaco. We selected patients complaining of asymmetrical periorbital features who
      received treatment with hyalurostructure and botulinum toxin injection in one or
      more sessions. Nine patients were selected and presented with the following
      symptoms: asymmetry of eyebrow position (2 patients), superior orbital hollow (2
      patients), tear trough (2 patients) and orbital volume (ocular prosthesis) (3
      patients). The objective was to evaluate the efficiency of combined treatment in
      one or more sessions on these oculofacial asymmetries. Hyaluronic acid injections
      were done using hyalurostructure. Hyaluronic acid gel (Restylane Lidocaine) was
      used with a 25 gauge reinforced micro-cannula (pix'l +, Thiebaud). This was
      combined with injections of botulinum toxin (azzalure*) to areas of muscular
      hyperaction. Follow-up was done at 1 year by clinical examination, photography
      and patient satisfaction. Complications of this combined treatment have been
      identified. RESULTS: At 1-year follow-up, 88% of patients were satisfied or very
      satisfied with their results. There were no more complications secondary to both
      treatments in the same session. It was not noticed more hematomas and bruises
      than in classical injection method. The action of toxin is constant over time
      despite the association of hyaluronic acid injections. CONCLUSION: Combined
      treatments with toxin and hyaluronic acid in oculofacial asymmetries are
      efficient and can be proposed in the same session. These treatments must be
      repeated to maintain and optimize muscle contraction and volume loss. Use of
      hyalurostructure and botulinum toxin treatment in the same session is effective
      and safe.

PMID- 22373037
TI  - The mathematical abilities of children with cochlear implants.
AB  - Research has shown that cochlear implants give rise to improvements in speech
      recognition and production in children with profound hearing loss but very few
      studies have explored mathematical abilities in these children. The current study
      compared the mathematical abilities of 24 children with cochlear implants (mean
      age 10 years 1 month) to a control group of 22 hearing children (mean age 9 years
      8 months). The math questions were categorized into questions that tapped into
      arithmetic or geometrical reasoning. It was predicted that the cochlear implant
      group would perform below the hearing group on the arithmetic questions but not
      the geometrical reasoning questions. Unexpectedly, the results showed that the
      cochlear implant group performed significantly below the hearing group on both
      types of math questions, but that this difference was mediated by language skill
      as assessed by vocabulary knowledge. The clinical implications of these results
      and possible future research results are considered.

PMID- 22373038
TI  - Does earlier use of productivity enhancers during cell line selection lead to the
      identification of more productive cell lines?

PMID- 22373039
TI  - Estimating heritability using family and unrelated individuals data.
AB  - For the family data from Genetic Analysis Workshop 17, we obtained heritability
      estimates of quantitative traits Q1 and Q4 using the ASSOC program in the
      S.A.G.E. software package. ASSOC is a family-based method that estimates
      heritability through the estimation of variance components. The covariate
      adjusted mean heritability was 0.650 for Q1 and 0.745 for Q4. For the unrelated
      individuals data, we estimated the heritability of Q1 as the proportion of total
      variance that can be accounted for by all single-nucleotide polymorphisms under
      an additive model. We examined a novel ordinary least-squares method, a naive
      restricted maximum-likelihood method, and a calibrated restricted maximum
      likelihood method. We applied the different methods to all 200 replicates for Q1.
      We observed that the ordinary least-squares method yielded many estimates outside
      the interval [0, 1]. The restricted maximum-likelihood estimates were more stable
      than the ordinary least-squares estimates. The naive restricted maximum
      likelihood method yielded an average estimate of 0.462 +/- 0.1, and the
      calibrated restricted maximum-likelihood method yielded an average of 0.535 +/-
      0.121. Our results demonstrate discrepancies in heritability estimates using the
      family data and the unrelated individuals data.

PMID- 22373042
TI  - Enhancing the discovery of rare disease variants through hierarchical modeling.
AB  - Advances in next-generation sequencing technology are enabling researchers to
      capture a comprehensive picture of genomic variation across large numbers of
      individuals with unprecedented levels of efficiency. The main analytic challenge
      in disease mapping is how to mine the data for rare causal variants among a sea
      of neutral variation. To achieve this goal, investigators have proposed a number
      of methods that exploit biological knowledge. In this paper, I propose applying a
      Bayesian stochastic search variable selection algorithm in this context. My
      multivariate method is inspired by the combined multivariate and collapsing
      method. In this proposed method, however, I allow an arbitrary number of
      different sources of biological knowledge to inform the model as prior
      distributions in a two-level hierarchical model. This allows rare variants with
      similar prior distributions to share evidence of association. Using the 1000
      Genomes Project single-nucleotide polymorphism data provided by Genetic Analysis
      Workshop 17, I show that through biologically informative prior distributions,
      some power can be gained over noninformative prior distributions.

PMID- 22373040
TI  - Construction and analysis of the protein-protein interaction networks for
      schizophrenia, bipolar disorder, and major depression.
AB  - BACKGROUND: Schizophrenia, bipolar disorder, and major depression are devastating
      mental diseases, each with distinctive yet overlapping epidemiologic
      characteristics. Microarray and proteomics data have revealed genes which
      expressed abnormally in patients. Several single nucleotide polymorphisms (SNPs)
      and mutations are associated with one or more of the three diseases.
      Nevertheless, there are few studies on the interactions among the disease
      associated genes and proteins. RESULTS: This study, for the first time,
      incorporated microarray and protein-protein interaction (PPI) databases to
      construct the PPI network of abnormally expressed genes in postmortem brain
      samples of schizophrenia, bipolar disorder, and major depression patients. The
      samples were collected from Brodmann area (BA) 10 of the prefrontal cortex.
      Abnormally expressed disease genes were selected by t-tests comparing the disease
      and control samples. These genes were involved in housekeeping functions (e.g.
      translation, transcription, energy conversion, and metabolism), in brain specific
      functions (e.g. signal transduction, neuron cell differentiation, and
      cytoskeleton), or in stress responses (e.g. heat shocks and biotic stress).The
      diseases were interconnected through several "switchboard"-like nodes in the PPI
      network or shared abnormally expressed genes. A "core" functional module which
      consisted of a tightly knitted sub-network of clique-5 and -4s was also observed.
      These cliques were formed by 12 genes highly expressed in both disease and
      control samples. CONCLUSIONS: Several previously unidentified disease marker
      genes and drug targets, such as SBNO2 (schizophrenia), SEC24C (bipolar disorder),
      and SRRT (major depression), were identified based on statistical and topological
      analyses of the PPI network. The shared or interconnecting marker genes may
      explain the shared symptoms of the studied diseases. Furthermore, the
      "switchboard" genes, such as APP, UBC, and YWHAZ, are proposed as potential
      targets for developing new treatments due to their functional and topological
      significance.

PMID- 22373043
TI  - Federated ontology-based queries over cancer data.
AB  - BACKGROUND: Personalised medicine provides patients with treatments that are
      specific to their genetic profiles. It requires efficient data sharing of
      disparate data types across a variety of scientific disciplines, such as
      molecular biology, pathology, radiology and clinical practice. Personalised
      medicine aims to offer the safest and most effective therapeutic strategy based
      on the gene variations of each subject. In particular, this is valid in oncology,
      where knowledge about genetic mutations has already led to new therapies. Current
      molecular biology techniques (microarrays, proteomics, epigenetic technology and
      improved DNA sequencing technology) enable better characterisation of cancer
      tumours. The vast amounts of data, however, coupled with the use of different
      terms - or semantic heterogeneity - in each discipline makes the retrieval and
      integration of information difficult. RESULTS: Existing software infrastructures
      for data-sharing in the cancer domain, such as caGrid, support access to
      distributed information. caGrid follows a service-oriented model-driven
      architecture. Each data source in caGrid is associated with metadata at
      increasing levels of abstraction, including syntactic, structural, reference and
      domain metadata. The domain metadata consists of ontology-based annotations
      associated with the structural information of each data source. However, caGrid's
      current querying functionality is given at the structural metadata level, without
      capitalising on the ontology-based annotations. This paper presents the design of
      and theoretical foundations for distributed ontology-based queries over cancer
      research data. Concept-based queries are reformulated to the target query
      language, where join conditions between multiple data sources are found by
      exploiting the semantic annotations. The system has been implemented, as a proof
      of concept, over the caGrid infrastructure. The approach is applicable to other
      model-driven architectures. A graphical user interface has been developed,
      supporting ontology-based queries over caGrid data sources. An extensive
      evaluation of the query reformulation technique is included. CONCLUSIONS: To
      support personalised medicine in oncology, it is crucial to retrieve and
      integrate molecular, pathology, radiology and clinical data in an efficient
      manner. The semantic heterogeneity of the data makes this a challenging task.
      Ontologies provide a formal framework to support querying and integration. This
      paper provides an ontology-based solution for querying distributed databases over
      service-oriented, model-driven infrastructures.

PMID- 22373045
TI  - Preoperative characteristics of high-Gleason disease predictive of favourable
      pathological and clinical outcomes at radical prostatectomy.
AB  - What's known on the subject? and What does the study add? Men with high-risk
      prostate cancer experience recurrence, metastases and death at the highest rate
      in the prostate cancer population. Pathological stage at radical prostatectomy
      (RP) is the greatest predictor of recurrence and mortality in men with high-grade
      disease. Preoperative models predicting outcome after RP are skewed by the large
      proportion of men with low- and intermediate-risk features; there is a paucity of
      data about preoperative criteria to identify men with high-grade cancer who may
      benefit from RP. The present study adds comprehensive biopsy data from a large
      cohort of men with high-grade prostate cancer at biopsy. By adding biopsy
      parameters, e.g. number of high-grade cores and >50% involvement of any core, to
      traditional predictors of outcome (prostate-specific antigen concentration,
      clinical stage and Gleason sum), we can better inform men who present with high
      grade prostate cancer as to their risk of favourable or unfavourable disease at
      RP. OBJECTIVE: To investigate preoperative characteristics that distinguish
      favourable and unfavourable pathological and clinical outcomes in men with high
      biopsy Gleason sum (8-10) prostate cancer to better select men who will most
      benefit from radical prostatectomy (RP). PATIENTS AND METHODS: The Institutional
      Review Board-approved institutional RP database (1982-2010) was analysed for men
      with high-Gleason prostate cancer on biopsy; 842 men were identified. The 10-year
      biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific
      survival (CSS) were calculated using the Kaplan-Meier method to verify favourable
      pathology as men with Gleason <8 at RP or <= pT3a compared with men with
      unfavourable pathology with Gleason 8-10 and pT3b or N1. Preoperative
      characteristics were compared using appropriate comparative tests. Logistic
      regression determined preoperative predictors of unfavourable pathology. RESULTS:
      There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS
      were 31.0%, 60.9% and 74.8%, respectively. In contrast, men with unfavourable
      pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%,
      29.1% and 52.3%, respectively (all P < 0.001). In multivariable logistic
      regression, a prostate-specific antigen (PSA) concentration of >10 ng/mL (odds
      ratio [OR] 2.24, 95% confidence interval [CI] 1.38-3.62, P = 0.001), advanced
      clinical stage (>= cT2b; OR 2.55, 95% CI 1.55-4.21, P < 0.001), Gleason pattern 9
      or 10 at biopsy (OR 2.55, 95% CI 1.59-4.09, P < 0.001), increasing number of
      cores positive with high-grade cancer (OR 1.16, 95% CI 1.01-1.34, P = 0.04) and
      >50% positive core involvement (OR 2.25, 95% CI 1.17-4.35, P = 0.015) were
      predictive of unfavourable pathology. CONCLUSIONS: Men with high-Gleason sum at
      biopsy are at high risk for biochemical recurrence, metastasis and death after
      RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have
      the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA
      concentration of >10 ng/mL, clinical stage >= T2b, Gleason pattern 9 or 10,
      increasing number of cores with high-grade cancer and >50% core involvement are
      predictive of unfavourable pathology.

PMID- 22373047
TI  - Soluble CD40 ligand is not elevated in plasma of patients with chronic
      spontaneous urticaria.

PMID- 22373048
TI  - Association tests for rare and common variants based on genotypic and phenotypic
      measures of similarity between individuals.
AB  - Genome-wide association studies have helped us identify thousands of common
      variants associated with several widespread complex diseases. However, for most
      traits, these variants account for only a small fraction of phenotypic variance
      or heritability. Next-generation sequencing technologies are being used to
      identify additional rare variants hypothesized to have higher effect sizes than
      the already identified common variants, and to contribute significantly to the
      fraction of heritability that is still unexplained. Several pooling strategies
      have been proposed to test the joint association of multiple rare variants,
      because testing them individually may not be optimal. Within a gene or genomic
      region, if there are both rare and common variants, testing their joint
      association may be desirable to determine their synergistic effects. We propose
      new methods to test the joint association of several rare and common variants
      with binary and quantitative traits. Our association test for quantitative traits
      is based on genotypic and phenotypic measures of similarity between pairs of
      individuals. For the binary trait or case-control samples, we recently proposed
      an association test based on the genotypic similarity between individuals. Here,
      we develop a modified version of this test for rare variants. Our tests can be
      used for samples taken from multiple subpopulations. The power of our test
      statistics for case-control samples and quantitative traits was evaluated using
      the GAW17 simulated data sets. Type I error rates for the proposed tests are well
      controlled. Our tests are able to identify some of the important causal genes in
      the GAW17 simulated data sets.

PMID- 22373050
TI  - kLa as a predictor for probe-independent mammalian cell bioprocesses in orbitally
      shaken bioreactors.

PMID- 22373051
TI  - Evaluation of a disposable stirred tank bioreactor for cultivation of mammalian
      cells.

PMID- 22373052
TI  - Enrichment analysis of genetic association in genes and pathways by aggregating
      signals from both rare and common variants.
AB  - New high-throughput sequencing technologies have brought forth opportunities for
      unbiased analysis of thousands of rare genomic variants in genome-wide
      association studies of complex diseases. Because it is hard to detect single rare
      variants with appreciable effect sizes at the population level, existing methods
      mostly aggregate effects of multiple markers by collapsing the rare variants in
      genes (or genomic regions). We hypothesize that a higher level of aggregation can
      further improve association signal strength. Using the Genetic Analysis Workshop
      17 simulated data, we test a two-step strategy that first applies a collapsing
      method in a gene-level analysis and then aggregates the gene-level test results
      by performing an enrichment analysis in gene sets. We find that the gene set
      approach which combines signals across multiple genes outperforms testing
      individual genes separately and that the power of the gene set enrichment test is
      further improved by proper adjustment of statistics to account for gene-wise
      differences.

PMID- 22373054
TI  - ClipCrop: a tool for detecting structural variations with single-base resolution
      using soft-clipping information.
AB  - BACKGROUND: Structural variations (SVs) change the structure of the genome and
      are therefore the causes of various diseases. Next-generation sequencing allows
      us to obtain a multitude of sequence data, some of which can be used to infer the
      position of SVs. METHODS: We developed a new method and implementation named
      ClipCrop for detecting SVs with single-base resolution using soft-clipping
      information. A soft-clipped sequence is an unmatched fragment in a partially
      mapped read. To assess the performance of ClipCrop with other SV-detecting tools,
      we generated various patterns of simulation data - SV lengths, read lengths, and
      the depth of coverage of short reads - with insertions, deletions, tandem
      duplications, inversions and single nucleotide alterations in a human chromosome.
      For comparison, we selected BreakDancer, CNVnator and Pindel, each of which
      adopts a different approach to detect SVs, e.g. discordant pair approach, depth
      of coverage approach and split read approach, respectively. RESULTS: Our method
      outperformed BreakDancer and CNVnator in both discovering rate and call accuracy
      in any type of SV. Pindel offered a similar performance as our method, but our
      method crucially outperformed for detecting small duplications. From our
      experiments, ClipCrop infer reliable SVs for the data set with more than 50 bases
      read lengths and 20x depth of coverage, both of which are reasonable values in
      current NGS data set. CONCLUSIONS: ClipCrop can detect SVs with higher
      discovering rate and call accuracy than any other tool in our simulation data
      set.

PMID- 22373055
TI  - Detection of rare functional variants using group ISIS.
AB  - Genome-wide association studies have been firmly established in investigations of
      the associations between common genetic variants and complex traits or diseases.
      However, a large portion of complex traits and diseases cannot be explained well
      by common variants. Detecting rare functional variants becomes a trend and a
      necessity. Because rare variants have such a small minor allele frequency (e.g.,
      <0.05), detecting functional rare variants is challenging. Group iterative sure
      independence screening (ISIS), a fast group selection tool, was developed to
      select important genes and the single-nucleotide polymorphisms within. The
      performance of the group ISIS and group penalization methods is compared for
      detecting important genes in the Genetic Analysis Workshop 17 data. The results
      suggest that the group ISIS is an efficient tool to discover genes and single
      nucleotide polymorphisms associated to phenotypes.

PMID- 22373056
TI  - Anti-diabetes effect of water containing hydrogen molecule and Pt nanoparticles.

PMID- 22373057
TI  - Single use bioreactors for the clinical production of monoclonal antibodies - a
      study to analyze the performance of a CHO cell line and the quality of the
      produced monoclonal antibody.

PMID- 22373059
TI  - A facile iodine(III)-mediated synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)
      [1,2,4]triazolo[4,3-a]pyridines via oxidation of 2-((3-aryl-1-phenyl-1H-pyrazol-4
      yl)methylene)-1-(pyridin-2-yl)hydrazines and their antimicrobial evaluations.
AB  - BACKGROUND: Fused heterocyclic 1,2,4-triazoles have acquired much importance
      because of their interesting biological properties. Although a number of methods
      have been reported in the literature which includes oxidation with phosphorus
      oxychloride, lead tetraacetate, bromine, etc., hypervalent iodine reagents have
      emerged as reagents of choice for various synthetically useful transformations
      due to their low toxicity, ready availability and ease of handling. RESULTS: A
      series of new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines
      4 has been conveniently synthesized by oxidative cyclization of 2-(3-aryl-1
      phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines 3 promoted with
      iodobenzene diacetate under mild conditions (up to 90% isolated yields). All the
      new compounds were tested in vitro for their antimicrobial activity. CONCLUSIONS:
      Iodine(III)-mediated oxidative approach has offered an easy access to new 3-(3
      aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4. The
      antibacterial and antifungal activities of newly synthesized compounds have
      proved them potent antimicrobial agents.

PMID- 22373060
TI  - Measuring the costs of biosecurity on poultry farms: a case study in broiler
      production in Finland.
AB  - BACKGROUND: Farm-level biosecurity provides the foundation for biosecurity along
      the entire production chain. Many risk management practices are constantly in
      place, regardless of whether there is a disease outbreak or not. Nonetheless, the
      farm-level costs of preventive biosecurity have rarely been assessed. We examined
      the costs incurred by preventive biosecurity for Finnish poultry farms. METHODS:
      We used a semi-structured phone interview and obtained results from 17 broiler
      producers and from 5 hatching egg producers, corresponding to about 10% of all
      producers in Finland. RESULTS: Our results indicate that the average cost of
      biosecurity is some 3.55 eurocent per bird for broiler producers (0.10 eurocent
      per bird per rearing day) and 75.7 eurocent per bird for hatching egg producers
      (0.27 eurocent per bird per rearing day). For a batch of 75,000 broilers, the
      total cost would be ?2,700. The total costs per bird are dependent on the annual
      number of birds: the higher the number of birds, the lower the cost per bird.
      This impact is primarily due to decreasing labour costs rather than direct
      monetary costs. Larger farms seem to utilise less labour per bird for biosecurity
      actions. There are also differences relating to the processor with which the
      producer is associated, as well as to the gender of the producer, with female
      producers investing more in biosecurity. Bird density was found to be positively
      related to the labour costs of biosecurity. This suggests that when the bird
      density is higher, greater labour resources need to be invested in their health
      and welfare and hence disease prevention. The use of coccidiostats as a
      preventive measure to control coccidiosis was found to have the largest cost
      variance between the producers, contributing to the direct costs. CONCLUSIONS:
      The redesign of cost-sharing in animal diseases is currently ongoing in the
      European Union. Before we can assert how the risk should be shared or resort to
      the 'polluter pays' principle, we need to understand how the costs are currently
      distributed. The ongoing study contributes towards understanding these issues.
      The next challenge is to link the costs of preventive biosecurity to the benefits
      thus acquired.

PMID- 22373061
TI  - Detecting rare functional variants using a wavelet-based test on quantitative and
      qualitative traits.
AB  - We conducted a genome-wide association study on the Genetic Analysis Workshop 17
      simulated unrelated individuals data using a multilocus score test based on
      wavelet transformation that we proposed recently. Wavelet transformation is an
      advanced smoothing technique, whereas the currently popular collapsing methods
      are the simplest way to smooth multilocus genotypes. The wavelet-based test
      suppresses noise from the data more effectively, which results in lower type I
      error rates. We chose a level-dependent threshold for the wavelet-based test to
      suppress the optimal amount of noise according to the data. We propose several
      remedies to reduce the inflated type I error rate: using a window of fixed size
      rather than a gene; using the Bonferroni correction rather than comparing to the
      maxima of test values for multiple testing corrections; and removing the
      influence of other factors by using residuals for the association test. A wavelet
      based test can detect multiple rare functional variants. Type I error rates can
      be controlled using the wavelet-based test combined with the mentioned remedies.

PMID- 22373063
TI  - Engineering CHO cells for improved central carbon and energy metabolism.

PMID- 22373062
TI  - Instructor feedback versus no instructor feedback on performance in a
      laparoscopic virtual reality simulator: a randomized educational trial.
AB  - BACKGROUND: Several studies have found a positive effect on the learning curve as
      well as the improvement of basic psychomotor skills in the operating room after
      virtual reality training. Despite this, the majority of surgical and
      gynecological departments encounter hurdles when implementing this form of
      training. This is mainly due to lack of knowledge concerning the time and human
      resources needed to train novice surgeons to an adequate level. The purpose of
      this trial is to investigate the impact of instructor feedback regarding time,
      repetitions and self-perception when training complex operational tasks on a
      virtual reality simulator. METHODS/DESIGN: The study population consists of
      medical students on their 4th to 6th year without prior laparoscopic experience.
      The study is conducted in a skills laboratory at a centralized university
      hospital. Based on a sample size estimation 98 participants will be randomized to
      an intervention group or a control group. Both groups have to achieve a
      predefined proficiency level when conducting a laparoscopic salpingectomy using a
      surgical virtual reality simulator. The intervention group receives standardized
      instructor feedback of 10 to 12 min a maximum of three times. The control group
      receives no instructor feedback. Both groups receive the automated feedback
      generated by the virtual reality simulator. The study follows the CONSORT
      Statement for randomized trials. Main outcome measures are time and repetitions
      to reach the predefined proficiency level on the simulator. We include focus on
      potential sex differences, computer gaming experience and self-perception.
      DISCUSSION: The findings will contribute to a better understanding of optimal
      training methods in surgical education. TRIAL REGISTRATION: NCT01497782.

PMID- 22373064
TI  - Development of 4H-pyridopyrimidines: a class of selective bacterial protein
      synthesis inhibitors.
AB  - BACKGROUND: We have identified a series of compounds that inhibit protein
      synthesis in bacteria. Initial IC50's in aminoacylation/translation (A/T) assays
      ranged from 3 to14 MUM. This series of compounds are variations on a 5,6,7,8
      tetrahydropyrido[4,3-d]pyrimidin-4-ol scaffold (e.g., 4H-pyridopyrimidine).
      METHODS: Greater than 80 analogs were prepared to investigate the structure
      activity relationship (SAR). Structural modifications included changes in the
      central ring and substituent modifications in its periphery focusing on the 2-
      and 6-positions. An A/T system was used to determine IC50 values for activity of
      the analogs in biochemical assays. Minimum inhibitory concentrations (MIC) were
      determined for each analog against cultures of Enterococcus faecalis, Moraxella
      catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus
      aureus, Escherichia coli tolC mutants and E. coli modified with PMBN. RESULTS:
      Modifications to the 2-(pyridin-2-yl) ring resulted in complete inactivation of
      the compounds. However, certain modifications at the 6-position resulted in
      increased antimicrobial potency. The optimized compounds inhibited the growth of
      E. faecalis, M. catarrhalis, H. influenzae, S. pneumoniae, S. aureus, E. coli
      tolC, mutants and E. coli modified with PMBN with MIC values of 4, <= 0.12, 1, 2,
      4, 1, 1 MUg/ml, respectively. IC50 values in biochemical assay were reduced to
      mid-nanomolar range. CONCLUSION: 4H-pyridopyrimidine analogs demonstrate broad
      spectrum inhibition of bacterial growth and modification of the compounds
      establishes SAR.

PMID- 22373065
TI  - Down-regulation of CD81 in human cells producing HCV-E1/E2 retroVLPs.

PMID- 22373067
TI  - Abstract withdrawn.

PMID- 22373066
TI  - Methods for adjusting population structure and familial relatedness in
      association test for collective effect of multiple rare variants on quantitative
      traits.
AB  - Because of the low frequency of rare genetic variants in observed data, the
      statistical power of detecting their associations with target traits is usually
      low. The collapsing test of collective effect of multiple rare variants is an
      important and useful strategy to increase the power; in addition, family data may
      be enriched with causal rare variants and therefore provide extra power. However,
      when family data are used, both population structure and familial relatedness
      need to be adjusted for the possible inflation of false positives. Using a
      unified mixed linear model and family data, we compared six methods to detect the
      association between multiple rare variants and quantitative traits. Through the
      analysis of 200 replications of the quantitative trait Q2 from the Genetic
      Analysis Workshop 17 data set simulated for 697 subjects from 8 extended
      families, and based on quantile-quantile plots under the null and receiver
      operating characteristic curves, we compared the false-positive rate and power of
      these methods. We observed that adjusting for pedigree-based kinship gives the
      best control for false-positive rate, whereas adjusting for marker-based identity
      by state slightly outperforms in terms of power. An adjustment based on a
      principal components analysis slightly improves the false-positive rate and
      power. Taking into account type-1 error, power, and computational efficiency, we
      find that adjusting for pedigree-based kinship seems to be a good choice for the
      collective test of association between multiple rare variants and quantitative
      traits using family data.

PMID- 22373069
TI  - Exploiting heterogeneous features to improve in silico prediction of peptide
      status - amyloidogenic or non-amyloidogenic.
AB  - BACKGROUND: Prediction of short stretches in protein sequences capable of forming
      amyloid-like fibrils is important in understanding the underlying cause of
      amyloid illnesses thereby aiding in the discovery of sequence-targeted anti
      aggregation pharmaceuticals. Due to the constraints of experimental molecular
      techniques in identifying such motif segments, it is highly desirable to develop
      computational methods to provide better and affordable in silico predictions.
      RESULTS: Accurate in silico prediction techniques of amyloidogenic peptide
      regions rely on the cooperation between informative features and classifier
      design. In this research article, we propose one such efficient fibril prediction
      implementation exploiting heterogeneous features based on bio-physio-chemical
      (BPC) properties, auto-correlation function of carefully selected amino acid
      indices and atomic composition within a protein fragment of amino acids in a
      window. In an attempt to get an optimal number of BPC features, an evolutionary
      Support Vector Machine (SVM) integrating a novel implementation of hybrid Genetic
      Algorithm termed Memetic Algorithm and SVM is utilized. Five prediction modules
      designed using Artificial Neural Network (ANN) models are trained with
      independent and integrated features in order to validate the fibril forming
      motifs. The results provide evidence that incorporating new feature namely auto
      correlation function besides BPC, attempt to strengthen the sequence interaction
      effect in forming the feature vector thereby obtaining better prediction quality
      in terms of sensitivity, specificity, Mathews Correlation Coefficient and Area
      under the Receiver Operating Characteristics curve. CONCLUSION: A significant
      improvement in performance is observed by introducing features like auto
      correlation function that maintains sequence order effect, in addition to the
      conventional BPC properties selected through a novel optimization strategy to
      predict the peptide status - amyloidogenic or non-amyloidogenic. The proposed
      approach achieves acceptable results, comparable to most online predictors.
      Besides, it compensates the lacuna in existing amyloid fibril prediction tools by
      maintaining equilibrium between sensitivity and specificity.

PMID- 22373071
TI  - Identifying rare disease variants in the Genetic Analysis Workshop 17 simulated
      data: a comparison of several statistical approaches.
AB  - Genome-wide association studies have been successful at identifying common
      disease variants associated with complex diseases, but the common variants
      identified have small effect sizes and account for only a small fraction of the
      estimated heritability for common diseases. Theoretical and empirical studies
      suggest that rare variants, which are much less frequent in populations and are
      poorly captured by single-nucleotide polymorphism chips, could play a significant
      role in complex diseases. Several new statistical methods have been developed for
      the analysis of rare variants, for example, the combined multivariate and
      collapsing method, the weighted-sum method and a replication-based method. Here,
      we apply and compare these methods to the simulated data sets of Genetic Analysis
      Workshop 17 and thereby explore the contribution of rare variants to disease
      risk. In addition, we investigate the usefulness of extreme phenotypes in
      identifying rare risk variants when dealing with quantitative traits. Finally, we
      perform a pathway analysis and show the importance of the vascular endothelial
      growth factor pathway in explaining different phenotypes. 

PMID- 22373072
TI  - Controlled expansion and differentiation of mesenchymal stem cells in a
      microcarrier based stirred bioreactor.

PMID- 22373073
TI  - Evaluation of disposable filtration systems for harvesting high cell density fed
      batch processes.

PMID- 22373074
TI  - Transient transfection of insect Sf-9 cells in TubeSpin((r)) bioreactor 50 tubes.

PMID- 22373075
TI  - Propensity score analysis in the Genetic Analysis Workshop 17 simulated data set
      on independent individuals.
AB  - Genetic Analysis Workshop 17 provided simulated phenotypes and exome sequence
      data for 697 independent individuals (209 case subjects and 488 control
      subjects). The disease liability in these data was influenced by multiple
      quantitative traits. We addressed the lack of statistical power in this small
      data set by limiting the genomic variants included in the study to those with
      potential disease-causing effect, thereby reducing the problem of multiple
      testing. After this adjustment, we could readily detect two common variants that
      were strongly associated with the quantitative trait Q1 (C13S523 and C13S522).
      However, we found no significant associations with the affected status or with
      any of the other quantitative traits, and the relationship between disease status
      and genomic variants remained obscure. To address the challenge of the
      multivariate phenotype, we used propensity scores to combine covariates with
      genetic risk factors into a single risk factor and created a new phenotype
      variable, the probability of being affected given the covariates. Using the
      propensity score as a quantitative trait in the case-control analysis, we again
      could identify the two common single-nucleotide polymorphisms (C13S523 and
      C13S522). In addition, this analysis captured the correlation between Q1 and the
      affected status and reduced the problem of multiple testing. Although the
      propensity score was useful for capturing and clarifying the genetic
      contributions of common variants to the disease phenotype and the mediating role
      of the quantitative trait Q1, the analysis did not increase power to detect rare
      variants.

PMID- 22373076
TI  - Cryptic variation in an ecological indicator organism: mitochondrial and nuclear
      DNA sequence data confirm distinct lineages of Baetis harrisoni Barnard
      (Ephemeroptera: Baetidae) in southern Africa.
AB  - BACKGROUND: Baetis harrisoni Barnard is a mayfly frequently encountered in river
      studies across Africa, but the external morphological features used for
      identifying nymphs have been observed to vary subtly between different geographic
      locations. It has been associated with a wide range of ecological conditions,
      including pH extremes of pH 2.9-10.0 in polluted waters. We present a molecular
      study of the genetic variation within B. harrisoni across 21 rivers in its
      distribution range in southern Africa. RESULTS: Four gene regions were examined,
      two mitochondrial (cytochrome c oxidase subunit I [COI] and small subunit
      ribosomal 16S rDNA [16S]) and two nuclear (elongation factor 1 alpha [EF1alpha]
      and phosphoenolpyruvate carboxykinase [PEPCK]). Bayesian and parsimony approaches
      to phylogeny reconstruction resulted in five well-supported major lineages, which
      were confirmed using a general mixed Yule-coalescent (GMYC) model. Results from
      the EF1alpha gene were significantly incongruent with both mitochondrial and
      nuclear (PEPCK) results, possibly due to incomplete lineage sorting of the
      EF1alpha gene. Mean between-clade distance estimated using the COI and PEPCK data
      was found to be an order of magnitude greater than the within-clade distance and
      comparable to that previously reported for other recognised Baetis species.
      Analysis of the Isolation by Distance (IBD) between all samples showed a small
      but significant effect of IBD. Within each lineage the contribution of IBD was
      minimal. Tentative dating analyses using an uncorrelated log-normal relaxed clock
      and two published estimates of COI mutation rates suggest that diversification
      within the group occurred throughout the Pliocene and mid-Miocene (~2.4-11.5
      mya). CONCLUSIONS: The distinct lineages of B. harrisoni correspond to
      categorical environmental variation, with two lineages comprising samples from
      streams that flow through acidic Table Mountain Sandstone and three lineages with
      samples from neutral-to-alkaline streams found within eastern South Africa,
      Malawi and Zambia. The results of this study suggest that B. harrisoni as it is
      currently recognised is not a single species with a wide geographic range and pH
      tolerance, but may comprise up to five species under the phylogenetic species
      concept, each with limited pH-tolerances, and that the B. harrisoni species group
      is thus in need of taxonomic review.

PMID- 22373077
TI  - Family- and population-based designs identify different rare causal variants.
AB  - Both family- and population-based samples are used to identify genetic variants
      associated with phenotypes. Each strategy has demonstrated advantages, but their
      ability to identify rare variants and genes containing rare variants is unclear.
      To compare these two study designs in the identification of rare causal variants,
      we applied various methods to the population- and family-based data simulated by
      the Genetic Analysis Workshop 17 with knowledge of the simulated model. Our
      results suggest that different variants can be identified by different study
      designs. Family-based and population-based study designs can be complementary in
      the identification of rare causal variants and should be considered in future
      studies.

PMID- 22373078
TI  - A qualitative study of stakeholder views of the conditions for and outcomes of
      successful clinical networks.
AB  - BACKGROUND: Clinical networks have been established to improve health outcomes
      and processes of care by implementing a range of innovations and undertaking
      projects based on perceived local need. Limited research exists on the necessary
      conditions required to bring about successful network outcomes and what
      characterises network success from the perspective of those involved in network
      initiatives. This qualitative study identified stakeholder views on i) the
      conditions for effective clinical networks; and ii) desirable outcomes of
      successful clinical networks. METHODS: Twenty-seven participants were interviewed
      using face-to-face audio-recorded semi-structured interviews. Transcribed data
      were coded and analysed to generate themes relating to the study aims. RESULTS:
      Five key factors represented as sub-themes were identified as important
      conditions for the establishment of successful clinical networks under the main
      theme of effective network structure, organisation and governance. These were:
      building relationships; effective leadership; strategic evidence-based workplans;
      adequate resources; and ability to implement and evaluate network initiatives.
      Two major themes encapsulated views on desirable outcomes of successful clinical
      networks: connecting and engaging which represented the outcomes of
      interdisciplinary and consumer collaboration and, partnerships with state health
      and local health services, and changing the landscape of care, which represented
      the importance of outcomes associated with improving services, care and patient
      health outcomes and implementing evidence-based practice. CONCLUSIONS: This study
      provides new knowledge on the conditions needed to establish successful clinical
      networks and on desirable outcomes arising from network projects and initiatives
      that are considered to be valuable by those working in or associated with
      clinical networks. This provides health services with information on what needs
      to be in place for successful networks and on the types of outcomes that can be
      considered for assessing network effectiveness.

PMID- 22373079
TI  - Two-stage analyses of sequence variants in association with quantitative traits.
AB  - We propose a two-stage design for the analysis of sequence variants in which a
      proportion of genes that show some evidence of association are identified
      initially and then followed up in an independent data set. We compare two
      different approaches. In both approaches the same summary measure (total number
      of minor alleles) is used for each gene in the initial analysis. In the first
      (simple) approach the same summary measure is used in the analysis of the
      independent data set. In the second (alternative) approach a more specific
      hypothesis is formed for the second stage; the summary measure used is the count
      of minor alleles in only those variants that in the initial data showed the same
      direction of association as was seen overall. We applied the methods to the
      simulated quantitative traits of Genetic Analysis Workshop 17, blind to the
      simulation model, and then evaluated their performance once the underlying model
      was known. Performance was similar for most genes, but the simple strategy
      considerably out-performed the alternative strategy for one gene, where most of
      the effect was due to very rare variants; this suggests that the alternative
      approach would not be advisable when the effect is seen in very rare variants.
      Further simulations are needed to investigate the potential superior power of the
      alternative method when some variants within a gene have opposing effects.
      Overall, the power to detect associations was low; this was also true when using
      a more powerful joint analysis that combined the two stages of the study.

PMID- 22373081
TI  - Pairwise shared genomic segment analysis in high-risk pedigrees: application to
      Genetic Analysis Workshop 17 exome-sequencing SNP data.
AB  - We applied our method of pairwise shared genomic segment (pSGS) analysis to high
      risk pedigrees identified from the Genetic Analysis Workshop 17 (GAW17) mini
      exome sequencing data set. The original shared genomic segment method focused on
      identifying regions shared by all case subjects in a pedigree; thus it can be
      sensitive to sporadic cases. Our new method examines sharing among all pairs of
      case subjects in a high-risk pedigree and then uses the mean sharing as the test
      statistic; in addition, the significance is assessed empirically based on the
      pedigree structure and linkage disequilibrium pattern of the single-nucleotide
      polymorphisms. Using all GAW17 replicates, we identified 18 unilineal high-risk
      pedigrees that contained excess disease (p < 0.01) and at least 15 meioses
      between case subjects. Eighteen rare causal variants were polymorphic in this set
      of pedigrees. Based on a significance threshold of 0.001, 72.2% (13/18) of these
      pedigrees were successfully identified with at least one region that contains a
      true causal variant. The regions identified included 4 of the possible 18
      polymorphic causal variants. On average, 1.1 true positives and 1.7 false
      positives were identified per pedigree. In conclusion, we have demonstrated the
      potential of our new pSGS method for localizing rare disease causal variants in
      common disease using high-risk pedigrees and exome sequence data.

PMID- 22373083
TI  - Metabolic enhancers: a new paradigm in cell culture media optimization.

PMID- 22373082
TI  - Focal adhesion kinase contributes to proliferative potential of ErbB2 mammary
      tumour cells but is dispensable for ErbB2 mammary tumour induction in vivo.
AB  - INTRODUCTION: Activation of focal adhesion kinase (FAK) is hypothesized to play
      an important role in the pathogenesis of human breast cancer. METHODS: To
      directly evaluate the role of FAK in mammary tumour progression, we have used a
      conditional FAK mouse model and mouse mammary tumour virus (MMTV)-driven Cre
      recombinase strain to inactivate FAK in the mammary epithelium of a transgenic
      mouse model of ErbB2 breast cancer. RESULTS: Although mammary epithelial
      disruption of FAK in this model resulted in both a delay in onset and a decrease
      in the number of neoplastic lesions, mammary tumours occurred in 100% of virgin
      female mice. All of the tumours and derived metastases that developed were
      proficient for FAK due to the absence of Cre recombinase expression. The
      hyperplastic epithelia where Cre-mediated recombination of FAK could be detected
      exhibited a profound proliferative defect. Consistent with these observations,
      disruption of FAK in established tumour cells resulted in reduced tumour growth
      that was associated with impaired proliferation. To avoid the selection for FAK
      proficient ErbB2 tumour epithelia through escape of Cre-mediated recombination,
      we next intercrossed the FAK conditional mice with a separate MMTV-driven ErbB2
      strain that co-expressed ErbB2 and Cre recombinase on the same transcriptional
      unit. CONCLUSIONS: While a delay in tumour induction was noted, FAK-deficient
      tumours arose in 100% of female animals indicating that FAK is dispensable for
      ErbB2 tumour initiation. In addition, the FAK-null ErbB2 tumours retained their
      metastatic potential. We further demonstrated that the FAK-related Pyk2 kinase is
      still expressed in these tumours and is associated with its downstream regulator
      p130Cas. These observations indicate that Pyk2 can functionally substitute for
      FAK in ErbB2 mammary tumour progression.

PMID- 22373084
TI  - Development of live cultural pandemic influenza vaccine Vector-Flu.

PMID- 22373085
TI  - Identification of ubiquitin/ubiquitin-like protein modification from tandem mass
      spectra with various PTMs.
AB  - BACKGROUND: Various solutions have been introduced for the identification of post
      translational modification (PTM) from tandem mass spectrometry (MS/MS) in
      proteomics field but the identification of peptide modifiers, such as Ubiquitin
      (Ub) and ubiquitin-like proteins (Ubls), is still a challenge. The fragmentation
      of peptide modifier produce complex shifted ion mass patterns in combination with
      other PTMs, which makes it difficult to identify and locate the PTMs on a protein
      sequence. Currently, most PTM identification methods do not consider the complex
      fragmentation of peptide modifier or deals it separately from the other PTMs.
      RESULTS: We developed an advanced PTM identification method that inspects
      possible ion patterns of the most known peptide modifiers as well as other known
      biological and chemical PTMs to make more comprehensive and accurate conclusion.
      The proposed method searches all detectable mass differences of measured peaks
      from their theoretical values and the mass differences within mass tolerance
      range are grouped as mass shift classes. The most possible locations of multiple
      PTMs including peptide modifiers can be determined by evaluating all possible
      scenarios generated by the combination of the qualified mass shift classes.The
      proposed method showed excellent performance in the test with simulated spectra
      having various PTMs including peptide modifiers and in the comparison with
      recently developed methods such as QuickMod and SUMmOn. In the analysis of HUPO
      Brain Proteome Project (BPP) datasets, the proposed method could find the
      ubiquitin modification sites that were not identified by other conventional
      methods. CONCLUSIONS: This work presents a novel method for identifying
      bothpeptide modifiers that generate complex fragmentation patternsand PTMs that
      are not fragmented during fragmentation processfrom tandem mass spectra.

PMID- 22373086
TI  - Silver triflate catalyzed synthesis of 3-aminoalkylated indoles and evaluation of
      their antibacterial activities.
AB  - An efficient, one-pot synthesis was developed for 3-aminoalkylated indoles by
      three-component coupling reaction of aldehydes, N-methylanilines, and indoles
      using AgOTf as a catalyst. A series of twenty 3-aminoalkylated indoles was
      evaluated for their antibacterial activities against both Gram negative and Gram
      positive bacteria. Compounds 4b and 4r showed good antibacterial activity against
      both Gram positive and Gram negative strains. However, inversing the property of
      substituent (from 4r to 4q) resulted in the significant fall in the magnitude of
      antibacterial activity against Escherichia coli.

PMID- 22373088
TI  - Application of Bayesian network structure learning to identify causal variant
      SNPs from resequencing data.
AB  - Using single-nucleotide polymorphism (SNP) genotypes from the 1000 Genomes
      Project pilot3 data provided for Genetic Analysis Workshop 17 (GAW17), we applied
      Bayesian network structure learning (BNSL) to identify potential causal SNPs
      associated with the Affected phenotype. We focus on the setting in which target
      genes that harbor causal variants have already been chosen for resequencing; the
      goal was to detect true causal SNPs from among the measured variants in these
      genes. Examining all available SNPs in the known causal genes, BNSL produced a
      Bayesian network from which subsets of SNPs connected to the Affected outcome
      were identified and measured for statistical significance using the
      hypergeometric distribution. The exploratory phase of analysis for pooled
      replicates sometimes identified a set of involved SNPs that contained more true
      causal SNPs than expected by chance in the Asian population. Analyses of single
      replicates gave inconsistent results. No nominally significant results were found
      in analyses of African or European populations. Overall, the method was not able
      to identify sets of involved SNPs that included a higher proportion of true
      causal SNPs than expected by chance alone. We conclude that this method, as
      currently applied, is not effective for identifying causal SNPs that follow the
      simulation model for the GAW17 data set, which includes many rare causal SNPs.

PMID- 22373092
TI  - Discerning key parameters influencing high productivity and quality through
      recognition of patterns in process data.

PMID- 22373094
TI  - Mitogenic effect of sericin on mammalian cells.

PMID- 22373095
TI  - 3D6 and 4B3: Recombinant expression of two anti-gp41 antibodies as dimeric and
      secretory IgA.

PMID- 22373096
TI  - Transient gene expression with CHO cells in conditioned medium: a study using
      TubeSpin((r)) bioreactors.

PMID- 22373097
TI  - Highly efficient, chemically defined and fully scalable biphasic production of
      vaccine viruses.

PMID- 22373098
TI  - On the viability of Escherichia coli cells lacking DNA topoisomerase I.
AB  - BACKGROUND: Manipulations of the DNA double helix during replication,
      transcription and other nucleic acid processing cause a change of DNA topology,
      which results in torsional stress. This stress is relaxed by DNA topoisomerases,
      a class of enzymes present in all domains of life. Negatively supercoiled DNA is
      relaxed by type IA topoisomerases that are widespread in bacteria, archaea and
      eukaryotes. In Escherichia coli there is conflicting data about viability of
      DeltatopA cells lacking topoisomerase I. RESULTS: In this study we sought to
      clarify whether E. coli cells lacking topoisomerase I are viable by using a
      plasmid-based lethality assay that allowed us to investigate the phenotype of
      DeltatopA cells without the presence of any compensatory mutations. Our results
      show that cells lacking topoisomerase I show an extreme growth defect and cannot
      be cultured without the accumulation of compensatory mutations. This growth
      defect can be partially suppressed by overexpression of topoisomerase III, the
      other type IA topoisomerase in E. coli, suggesting that the accumulation of
      torsional stress is, at least partially, responsible for the lethality of
      DeltatopA cells. The absence of RNase HI strongly exacerbates the phenotype of
      cells lacking topoisomerase I, which supports the idea that the processing of
      RNA:DNA hybrids is vitally important in DeltatopA cells. However, we did not
      observe suppression of the DeltatopA phenotype by increasing the level of R-loop
      processing enzymes, such as RNase HI or RecG. CONCLUSIONS: Our data show
      unambiguously that E. coli cells are not viable in the absence of DNA
      topoisomerase I without the presence of compensatory mutations. Furthermore, our
      data suggest that the accumulation of R-loops is not the primary reason for the
      severe growth defect of cells lacking topoisomerase I, which is in contrast to
      the current literature. Potential reasons for this discrepancy are discussed.

PMID- 22373099
TI  - A new protein-ligand binding sites prediction method based on the integration of
      protein sequence conservation information.
AB  - BACKGROUND: Prediction of protein-ligand binding sites is an important issue for
      protein function annotation and structure-based drug design. Nowadays, although
      many computational methods for ligand-binding prediction have been developed,
      there is still a demanding to improve the prediction accuracy and efficiency. In
      addition, most of these methods are purely geometry-based, if the prediction
      methods improvement could be succeeded by integrating physicochemical or sequence
      properties of protein-ligand binding, it may also be more helpful to address the
      biological question in such studies. RESULTS: In our study, in order to
      investigate the contribution of sequence conservation in binding sites prediction
      and to make up the insufficiencies in purely geometry based methods, a simple yet
      efficient protein-binding sites prediction algorithm is presented, based on the
      geometry-based cavity identification integrated with sequence conservation
      information. Our method was compared with the other three classical tools:
      PocketPicker, SURFNET, and PASS, and evaluated on an existing comprehensive
      dataset of 210 non-redundant protein-ligand complexes. The results demonstrate
      that our approach correctly predicted the binding sites in 59% and 75% of cases
      among the TOP1 candidates and TOP3 candidates in the ranking list, respectively,
      which performs better than those of SURFNET and PASS, and achieves generally a
      slight better performance with PocketPicker. CONCLUSIONS: Our work has
      successfully indicated the importance of the sequence conservation information in
      binding sites prediction as well as provided a more accurate way for binding
      sites identification.

PMID- 22373100
TI  - Pathway analysis following association study.
AB  - Genome-wide association studies often emphasize single-nucleotide polymorphisms
      with the smallest p-values with less attention given to single-nucleotide
      polymorphisms not ranked near the top. We suggest that gene pathways contain
      valuable information that can enable identification of additional associations.
      We used gene set information to identify disease-related pathways using three
      methods: gene set enrichment analysis (GSEA), empirical enrichment p-values, and
      Ingenuity pathway analysis (IPA). Association tests were performed for common
      single-nucleotide polymorphisms and aggregated rare variants with traits Q1 and
      Q4. These pathway methods were evaluated by type I error, power, and the ranking
      of the VEGF pathway, the gene set used in the simulation model. GSEA and IPA had
      high power for detecting the VEGF pathway for trait Q1 (91.2% and 93%,
      respectively). These two methods were conservative with deflated type I errors
      (0.0083 and 0.0072, respectively). The VEGF pathway ranked 1 or 2 in 123 of 200
      replicates using IPA and ranked among the top 5 in 114 of 200 replicates for
      GSEA. The empirical enrichment method had lower power and higher type I error.
      Thus pathway analysis approaches may be useful in identifying biological pathways
      that influence disease outcomes.

PMID- 22373101
TI  - Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic
      insights into the anti-herpetic mode of action of herbal drug withaferin A.
AB  - BACKGROUND: Herpes Simplex Virus 1 and 2 causes several infections in humans
      including cold sores and encephalitis. Previous antiviral studies on herpes
      viruses have focussed on developing nucleoside analogues that can inhibit viral
      polymerase and terminate the replicating viral DNA. However, these drugs bear an
      intrinsic non-specificity as they can also inhibit cellular polymerase apart from
      the viral one. The present study is an attempt to elucidate the action mechanism
      of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus
      providing an evidence for its development as a novel anti-herpetic drug. RESULTS:
      Withaferin A was found to bind very similarly to that of the previously reported
      4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617,
      Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning
      of the polymerase. A comparison of the conformation obtained from docking and the
      molecular dynamics simulations shows that substantial changes in the binding
      conformations have occurred. These results indicate that the initial receptor
      ligand interaction observed after docking can be limited due to the receptor
      rigid docking algorithm and that the conformations and interactions observed
      after simulation runs are more energetically favoured. CONCLUSIONS: We have
      performed docking and molecular dynamics simulation studies to elucidate the
      binding mechanism of prospective herbal drug withaferin A onto the structure of
      DNA polymerase of Herpes simplex virus. Our docking simulations results give high
      binding affinity of the ligand to the receptor. Long de novo MD simulations for
      10 ns performed allowed us to evaluate the dynamic behaviour of the system
      studied and corroborate the docking results, as well as identify key residues in
      the enzyme-inhibitor interactions. The present MD simulations support the
      hypothesis that withaferin A is a potential ligand to target/inhibit DNA
      polymerase of the Herpes simplex virus. Results of these studies will also guide
      the design of selective inhibitors of DNA POL with high specificity and potent
      activity in order to strengthen the therapeutic arsenal available today against
      the dangerous biological warfare agent represented by Herpes Simplex Virus.

PMID- 22373102
TI  - Efficacy of endoluminal interventional therapy in diabetic peripheral arterial
      occlusive disease: a retrospective trial.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy of
      interventional therapy for peripheral arterial occlusive disease and the
      difference between diabetic patients and non-diabetic patients. METHODS: 139
      consecutive patients between September 2006 and September 2010 who underwent
      percutaneous lower extremity revascularization for arterial lesions were divided
      into diabetes group (n = 62) and non-diabetes group (n = 77). Before
      intervention, rest ankle brachial indexes and three dimensional computed
      tomography angiography from abdominal aorta to tiptoe were performed. The
      interventional treatments included angioplasty with or without stenting. The
      clinical outcomes included rest ankle-brachial indexes, primary patency rates,
      secondary patency rates and limb-salvage rates for 6-month, 12-month, 24-month
      and 36-month after treatment. The primary and secondary patency rates of all
      interventions and the limb-salvage rates of the patients are illustrated by
      Kaplan-Meier curves and compared by log-rank analysis. RESULTS: The
      interventional operation success rates were 98.4% (61/62) in diabetes group and
      100% (77/77) in non-diabetes group. The re-interventional operation success rates
      were 85.7% (18/21) in diabetes group and 76.9% (20/26) in non-diabetes group. The
      mean value of ankle brachial indexes was significantly increased after
      intervention (0.397 +/- 0.125 versus 0.779 +/- 0.137, t = -25.780, P < 0.001) in
      diabetes group and (0.406 +/- 0.101 versus 0.786 +/- 0.121, t = -37.221, P <
      0.001) in non-diabetes group. Perioperative 30-day mortality was 0%. Major
      complications included groin hematoma in 7.2%, and pseudoaneurysm formation 2.2%.
      In diabetes group, 6, 12, 24, and 36-month primary patency rates were 88.7% +/-
      4.0%, 62.3% +/- 6.6%, 55.3% +/- 7.0%, and 46.5% +/- 7.5%; secondary patency rates
      were 93.5% +/- 3.1%, 82.3% +/- 5.1%, 70.8% +/- 6.5%, and 65.7% +/- 7%; limb
      salvage rates were 95.2% +/- 2.7%, 87.7% +/- 4.4%, 85.5% +/- 4.8%, and 81.9% +/-
      5.8%. In non-diabetes group, 6, 12, 24, and 36-month primary patency rates were
      90.9% +/- 3.3%, 71.8% +/- 5.4%, 71.8% +/- 5.4%, and 60.9% +/- 6.2%; secondary
      patency rates were 96.1% +/- 2.2%, 91.6% +/- 3.3%, 82.7% +/- 4.8%, and 71.8% +/-
      6.2%; limb-salvage rates were 97.4% +/- 1.8%, 94.4% +/- 2.7%, 90.6% +/- 3.7%, and
      83.1% +/- 5.4%. The differences between two groups were not significant (P >
      0.05). CONCLUSION: With a low risk of morbidity and mortality, the percutaneous
      revascularization accepted by patients does not affect ultimate necessary
      surgical revascularization and consequently should be considered as the preferred
      therapy for chronic lower extremity ischemia. The efficacy and prognosis of
      interventional therapy in diabetic patients is similar that in non-diabetic
      patients.

PMID- 22373104
TI  - Genetic signal maximization using environmental regression.
AB  - Joint analyses of correlated phenotypes in genetic epidemiology studies are
      common. However, these analyses primarily focus on genetic correlation between
      traits and do not take into account environmental correlation. We describe a
      method that optimizes the genetic signal by accounting for stochastic
      environmental noise through joint analysis of a discrete trait and a correlated
      quantitative marker. We conducted bivariate analyses where heritability and the
      environmental correlation between the discrete and quantitative traits were
      calculated using Genetic Analysis Workshop 17 (GAW17) family data. The resulting
      inverse value of the environmental correlation between these traits was then used
      to determine a new beta coefficient for each quantitative trait and was
      constrained in a univariate model. We conducted genetic association tests on
      7,087 nonsynonymous SNPs in three GAW17 family replicates for Affected status
      with the beta coefficient fixed for three quantitative phenotypes and compared
      these to an association model where the beta coefficient was allowed to vary.
      Bivariate environmental correlations were 0.64 (+/- 0.09) for Q1, 0.798 (+/-
      0.076) for Q2, and -0.169 (+/- 0.18) for Q4. Heritability of Affected status
      improved in each univariate model where a constrained beta coefficient was used
      to account for stochastic environmental effects. No genome-wide significant
      associations were identified for either method but we demonstrated that
      constraining beta for covariates slightly improved the genetic signal for
      Affected status. This environmental regression approach allows for increased
      heritability when the beta coefficient for a highly correlated quantitative
      covariate is constrained and increases the genetic signal for the discrete trait.

PMID- 22373105
TI  - Study of a recombinant CHO cell line producing a monoclonal antibody by ATF or
      TFF external filter perfusion in a WAVE BioreactorTM.

PMID- 22373106
TI  - Osteogenic Differentiation of adipose mesenchymal stem cells with BMP-2 embedded
      microspheres in a rotating bed bioreactor.

PMID- 22373107
TI  - Distance-based phenotypic association analysis of DNA sequence data.
AB  - As the cost of sequencing decreases, the demand for association tests that use
      exhaustive DNA sequence information increases. One such association test is
      multivariate distance matrix regression (MDMR). We explore some of the features
      of MDMR using Genetic Analysis Workshop 17 simulated data in search of potential
      improvements in distance measures. We used genotype data from 697 unrelated
      individuals, in 200 replications, to test the power of MDMR to detect 13 trait Q2
      causative genes based on the Euclidean distance metric. We also estimated the
      false-positive rate of MDMR using 508 control genes. In addition, we compared
      MDMR with Mantel's test and collapsing analysis for rare variants. MDMR performed
      comparably well even with the Euclidean distance measure.

PMID- 22373109
TI  - A truly green synthesis of alpha-aminonitriles via Strecker reaction.
AB  - BACKGROUND: The classical Strecker reaction is one of the simplest and most
      economical methods for the synthesis of racemic alpha-aminonitriles (precursor of
      alpha-amino acids) and pharmacologically useful compounds. RESULTS: Indium powder
      in water is shown to act as a very efficient catalyst for one-pot, three
      component synthesis of alpha-aminonitriles from diverse amines, aldehydes and
      TMSCN. This general rapid method is applicable to a wide range of amines and
      aldehydes and produces products in excellent yield. CONCLUSIONS: The present one
      pot, three-component environmentally benign procedure for the synthesis of alpha
      aminonitriles will find application in the synthesis of complex biologically
      active molecules.

PMID- 22373110
TI  - Use of Bayesian networks to dissect the complexity of genetic disease:
      application to the Genetic Analysis Workshop 17 simulated data.
AB  - Complex diseases are often the downstream event of a number of risk factors,
      including both environmental and genetic variables. To better understand the
      mechanism of disease onset, it is of great interest to systematically investigate
      the crosstalk among various risk factors. Bayesian networks provide an intuitive
      graphical interface that captures not only the association but also the
      conditional independence and dependence structures among the variables, resulting
      in sparser relationships between risk factors and the disease phenotype than
      traditional correlation-based methods. In this paper, we apply a Bayesian network
      to dissect the complex regulatory relationships among disease traits and various
      risk factors for the Genetic Analysis Workshop 17 simulated data. We use the
      Bayesian network as a tool for the risk prediction of disease outcome.

PMID- 22373111
TI  - Disposable bioreactors: from process development to production.

PMID- 22373112
TI  - Proteomic and metabolomic characterization of CHO DP-12 cell lines with different
      high passage histories.

PMID- 22373113
TI  - Does pathway analysis make it easier for common variants to tag rare ones?
AB  - Analyzing sequencing data is difficult because of the low frequency of rare
      variants, which may result in low power to detect associations. We consider
      pathway analysis to detect multiple common and rare variants jointly and to
      investigate whether analysis at the pathway level provides an alternative
      strategy for identifying susceptibility genes. Available pathway analysis methods
      for data from genome-wide association studies might not be efficient because
      these methods are designed to detect common variants. Here, we investigate the
      performance of several existing pathway analysis methods for sequencing data. In
      particular, we consider the global test, which does not consider linkage
      disequilibrium between the variants in a gene. We improve the performance of the
      global test by assigning larger weights to rare variants, as proposed in the
      weighted-sum approach. Our conclusion is that straightforward application of
      pathway analysis is not satisfactory; hence, when common and rare variants are
      jointly analyzed, larger weights should be assigned to rare variants.

PMID- 22373114
TI  - Successful identification of rare variants using oligogenic segregation analysis
      as a prioritizing tool for whole-exome sequencing studies.
AB  - We aim to identify rare variants that have large effects on trait variance using
      a cost-efficient strategy. We use an oligogenic segregation analysis as a
      prioritizing tool for whole-exome sequencing studies to identify families more
      likely to harbor rare variants, by estimating the mean number of quantitative
      trait loci (QTLs) in each family. We hypothesize that families with additional
      QTLs, relative to the other families, are more likely to segregate functional
      rare variants. We test the association of rare variants with the traits only in
      regions where at least modest evidence of linkage with the trait is observed,
      thereby reducing the number of tests performed. We found that family 7 harbored
      an estimated two, one, and zero additional QTLs for traits Q1, Q2, and Q4,
      respectively. Two rare variants (C4S4935 and C6S2981) segregating in family 7
      were associated with Q1 and explained a substantial proportion of the observed
      linkage signal. These rare variants have 31 and 22 carriers, respectively, in the
      128-member family and entered through a single but different founder. For Q2, we
      found one rare variant unique to family 7 that showed small effect and weak
      evidence of association; this was a false positive. These results are a proof of
      principle that prioritizing the sequencing of carefully selected extended
      families is a simple and cost-efficient design strategy for sequencing studies
      aiming at identifying functional rare variants.

PMID- 22373118
TI  - Challenges in scaling up a perfusion process.

PMID- 22373119
TI  - Creating new opportunities in process control through radio frequency impedance
      spectroscopy.

PMID- 22373122
TI  - Utilization of multifrequency permittivity measurements in addition to biomass
      monitoring.

PMID- 22373120
TI  - Association of body temperature and antipyretic treatments with mortality of
      critically ill patients with and without sepsis: multi-centered prospective
      observational study.
AB  - INTRODUCTION: Fever is frequently observed in critically ill patients. An
      independent association of fever with increased mortality has been observed in
      non-neurological critically ill patients with mixed febrile etiology. The
      association of fever and antipyretics with mortality, however, may be different
      between infective and non-infective illness. METHODS: We designed a prospective
      observational study to investigate the independent association of fever and the
      use of antipyretic treatments with mortality in critically ill patients with and
      without sepsis. We included 1,425 consecutive adult critically ill patients
      (without neurological injury) requiring >48 hours intensive care admitted in 25
      ICUs. We recorded four-hourly body temperature and all antipyretic treatments
      until ICU discharge or 28 days after ICU admission, whichever occurred first. For
      septic and non-septic patients, we separately assessed the association of maximum
      body temperature during ICU stay (MAXICU) and the use of antipyretic treatments
      with 28-day mortality. RESULTS: We recorded body temperature 63,441 times.
      Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found
      that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or
      acetaminophen independently increased 28-day mortality for septic patients
      (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but
      not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15,
      acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate
      with mortality in either group. Relative to the reference range (MAXICU >= 39.5
      degrees C increased risk of 28-day mortality in non-septic patients (adjusted
      odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47,
      P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (>=39.5
      degrees C) independently associated with mortality, without association of
      administration of NSAIDs or acetaminophen with mortality. In contrast, in septic
      patients, administration of NSAIDs or acetaminophen independently associated with
      28-day mortality, without association of fever with mortality. These findings
      suggest that fever and antipyretics may have different biological or clinical or
      both implications for patients with and without sepsis. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00940654.

PMID- 22373124
TI  - Utilizing Roche Cedex Bio analyzer for in process monitoring in biotech
      production.

PMID- 22373123
TI  - Serum contents of endocannabinoids are correlated with blood pressure in
      depressed women.
AB  - BACKGROUND: Depression is known to be a risk factor for cardiovascular diseases
      but the underlying mechanisms remain unclear. Since recent preclinical evidence
      suggests that endogenous agonists of cannabinoid receptors (endocannabinoids) are
      involved in both cardiovascular function and depression, we asked whether
      endocannabinoids correlated with either in humans. RESULTS: Resting blood
      pressure and serum content of endocannabinoids in ambulatory, medication-free,
      female volunteers with depression (n = 28) and their age- and ethnicity-matched
      controls (n = 27) were measured. In females with depression, both diastolic and
      mean arterial blood pressures were positively correlated with serum contents of
      the endocannabinoids, N-arachidonylethanolamine (anandamide) and 2
      arachidonoylglycerol. There was no correlation between blood pressure and
      endocannabinoids in control subjects. Furthermore, depressed women had
      significantly higher systolic blood pressure than control subjects. A larger body
      mass index was also found in depressed women, however, it was not significantly
      correlated with serum endocannabinoid contents. CONCLUSIONS: This preliminary
      study raises the possibility that endocannabinoids play a role in blood pressure
      regulation in depressives with higher blood pressure, and suggests an
      interrelationship among endocannabinoids, depression and cardiovascular risk
      factors in women.

PMID- 22373126
TI  - Gene-based partial least-squares approaches for detecting rare variant
      associations with complex traits.
AB  - Genome-wide association studies are largely based on single-nucleotide
      polymorphisms and rest on the common disease/common variants (single-nucleotide
      polymorphisms) hypothesis. However, it has been argued in the last few years and
      is well accepted now that rare variants are valuable for studying common
      diseases. Although current genome-wide association studies have successfully
      discovered many genetic variants that are associated with common diseases,
      detecting associated rare variants remains a great challenge. Here, we propose
      two partial least-squares approaches to aggregate the signals of many single
      nucleotide polymorphisms (SNPs) within a gene to reveal possible genetic effects
      related to rare variants. The availability of the 1000 Genomes Project offers us
      the opportunity to evaluate the effectiveness of these two gene-based approaches.
      Compared to results from a SNP-based analysis, the proposed methods were able to
      identify some (rare) SNPs that were missed by the SNP-based analysis.

PMID- 22373127
TI  - Hydrodynamic stress in orbitally shaken bioreactors.

PMID- 22373129
TI  - Medium and feed optimization for fed-batch production of a monoclonal antibody in
      CHO cells.

PMID- 22373130
TI  - A framework for publishing primary biodiversity data.

PMID- 22373128
TI  - Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of
      5-HT1A receptor and serotonin transporter in the brain of foetal rat.
AB  - BACKGROUND: Many studies have found that stress before or during pregnancy is
      linked to an increased incidence of behavioural disorders in offspring. However,
      few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity
      and the serotonergic system as a consequence of pregestational stress. In the
      present study, we investigated the effect of pre-gestational stress on HPA axis
      activity in maternal rats and their foetuses and examined whether changes in HPA
      axis activity of maternal rats produced functional changes in the serotonergic
      system in the brain of foetuses. RESULTS: We used the behavioural tests to assess
      the model of chronic unpredictable stress (CUS) in maternal rats. We found the
      activity in the open field and sucrose consumption was lower for rats with CUS
      than for the controls. Body weight but not brain weight was higher for control
      foetuses than those from the CUS group. Serum corticosterone and corticotrophin
      releasing hormone levels were significantly higher for mothers with CUS before
      pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine
      (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS
      group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were
      lower in the hippocampus in foetuses in the CUS group than in the control group.
      Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS
      group and in the control group. The ratio of 5-HIAA to 5-HT was significantly
      lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A
      receptor were significantly lower in the foetal hippocampus in the CUS group than
      in the control group, with no significant difference in the hypothalamus. The
      levels of serotonin transporter (SERT) were lower in both the foetal hippocampus
      and foetal hypothalamus in the CUS group than in the control group. CONCLUSIONS:
      Our data demonstrate that pre-gestational stress alters HPA axis activity in
      maternal rats and their foetuses, which is associated with functional changes in
      5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels
      of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

PMID- 22373131
TI  - Using the posterior distribution of deviance to measure evidence of association
      for rare susceptibility variants.
AB  - Aitkin recently proposed an integrated Bayesian/likelihood approach that he
      claims is general and simple. We have applied this method, which does not rely on
      informative prior probabilities or large-sample results, to investigate the
      evidence of association between disease and the 16 variants in the KDR gene
      provided by Genetic Analysis Workshop 17. Based on the likelihood of logistic
      regression models and considering noninformative uniform prior probabilities on
      the coefficients of the explanatory variables, we used a random walk Metropolis
      algorithm to simulate the distributions of deviance and deviance difference. The
      distribution of probability values and the distribution of the proportions of
      positive deviance differences showed different locations, but the direction of
      the shift depended on the genetic factor. For the variant with the highest minor
      allele frequency and for any rare variant, standard logistic regression showed a
      higher power than the novel approach. For the two variants with the strongest
      effects on Q1 under a type I error rate of 1%, the integrated approach showed a
      higher power than standard logistic regression. The advantages and limitations of
      the integrated Bayesian/likelihood approach should be investigated using
      additional regions and considering alternative regression models and collapsing
      methods.

PMID- 22373132
TI  - In silico modification of suberoylanilide hydroxamic acid (SAHA) as potential
      inhibitor for class II histone deacetylase (HDAC).
AB  - BACKGROUND: The cervical cancer is the second most prevalent cancer for the woman
      in the world. It is caused by the oncogenic human papilloma virus (HPV). The
      inhibition activity of histone deacetylase (HDAC) is a potential strategy for
      cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is widely known as a low
      toxicity HDAC inhibitor. This research presents in silico SAHA modification by
      utilizing triazole, in order to obtain a better inhibitor. We conducted docking
      of the SAHA inhibitor and 12 modified versions to six class II HDAC enzymes, and
      then proceeded with drug scanning of each one of them. RESULTS: The docking
      results show that the 12 modified inhibitors have much better binding affinity
      and inhibition potential than SAHA. Based on drug scan analysis, six of the
      modified inhibitors have robust pharmacological attributes, as revealed by drug
      likeness, drug score, oral bioavailability, and toxicity levels. CONCLUSIONS: The
      binding affinity, free energy and drug scan screening of the best inhibitors have
      shown that 1c and 2c modified inhibitors are the best ones to inhibit class II
      HDAC.

PMID- 22373133
TI  - SNP set analysis for detecting disease association using exon sequence data.
AB  - Rare variants are believed to play an important role in disease etiology. Recent
      advances in high-throughput sequencing technology enable investigators to
      systematically characterize the genetic effects of both common and rare variants.
      We introduce several approaches that simultaneously test the effects of common
      and rare variants within a single-nucleotide polymorphism (SNP) set based on
      logistic regression models and logistic kernel machine models. Gene-environment
      interactions and SNP-SNP interactions are also considered in some of these
      models. We illustrate the performance of these methods using the unrelated
      individuals data from Genetic Analysis Workshop 17. Three true disease genes
      (FLT1, PIK3C3, and KDR) were consistently selected using the proposed methods. In
      addition, compared to logistic regression models, the logistic kernel machine
      models were more powerful, presumably because they reduced the effective number
      of parameters through regularization. Our results also suggest that a screening
      step is effective in decreasing the number of false-positive findings, which is
      often a big concern for association studies.

PMID- 22373134
TI  - Neuroprotective effects of 3,5-di-o-caffeoylquinic acid in vitro and in vivo.

PMID- 22373135
TI  - Genome-wide case-control study in GAW17 using coalesced rare variants.
AB  - Genome-wide association studies have successfully identified numerous loci at
      which common variants influence disease risks or quantitative traits of interest.
      Despite these successes, the variants identified by these studies have generally
      explained only a small fraction of the variations in the phenotype. One
      explanation may be that many rare variants that are not included in the common
      genotyping platforms may contribute substantially to the genetic variations of
      the diseases. Next-generation sequencing, which would better allow for the
      analysis of rare variants, is now becoming available and affordable; however, the
      presence of a large number of rare variants challenges the statistical endeavor
      to stably identify these disease-causing genetic variants. We conduct a genome
      wide association study of Genetic Analysis Workshop 17 case-control data produced
      by the next-generation sequencing technique and propose that collapsing rare
      variants within each genetic region through a supervised dimension reduction
      algorithm leads to several macrovariants constructed for rare variants within
      each genetic region. A simultaneous association of the phenotype to all common
      variants and macrovariants is undertaken using a linear discriminant analysis
      using the penalized orthogonal-components regression algorithm. The results
      suggest that the proposed analysis strategy shows promise but needs further
      development.

PMID- 22373136
TI  - A rapid, convenient, solventless green approach for the synthesis of oximes using
      grindstone chemistry.
AB  - BACKGROUND: Synthesis of oximes is an important reaction in organic chemistry,
      because these versatile oximes are used for protection, purification, and
      characterization of carbonyl compounds. Nitriles, amides via Beckmann
      rearrangement, nitro compounds, nitrones, amines, and azaheterocycles can be
      synthesised from oximes. They also find applications for selective alpha
      activation. In inorganic chemistry, oximes act as a versatile ligand.Several
      procedures for the preparation of oximes exist, but, most of them have not
      addressed the green chemistry issue. They are associated with generation of
      pollutants, requirement of high reaction temperature, low yields, lack of a
      generalized procedure, etc. Hence, there is a demand for developing an efficient,
      convenient, and non-polluting or less polluting alternative method for the
      preparation of oximes. In this context, bismuth compounds are very useful as they
      are cheap in general, commercially available, air stable crystalline solids,
      safe, and non-toxic, hence easy to handle. RESULTS: Carbonyl compounds
      (aliphatic, heterocyclic, and aromatic) were converted into the corresponding
      oximes in excellent yields by simply grinding the reactants at room temperature
      without using any solvent in the presence of Bi2O3. Most importantly, this method
      minimizes waste disposal problems, provides a simple yet efficient example of
      unconventional methodology and requires short time. CONCLUSIONS: We have
      developed a novel, quick, environmentally safe, and clean synthesis of aldoximes
      and ketoximes under solvent-free grinding condition.

PMID- 22373138
TI  - Mutational load analysis of unrelated individuals.
AB  - Evolutionary genetic models predict that the cumulative effect of rare
      deleterious mutations across the genome-known as mutational load burden-increases
      the susceptibility to complex disease. To test the mutational load burden
      hypothesis, we adopted a two-tiered approach: assessing the impact of whole-exome
      minor allele load burden and then conducting individual-gene screening. For our
      primary analysis, we examined various minor allele frequency (MAF) thresholds and
      weighting schemes to examine the overall effect of minor allele load on affection
      status. We found a consistent association between minor allele load and affection
      status, but this effect did not markedly increase within rare and/or functional
      single-nucleotide polymorphisms (SNPs). Our follow-up analysis considered minor
      allele load in individual genes to see whether only one or a few genes were
      driving the overall effect. Examining our most significant result-minor allele
      load of nonsynonymous SNPs with MAF < 2.4%-we detected no significantly
      associated genes after Bonferroni correction for multiple testing. After
      moderately significant genes (p < 0.05) were removed, the overall effect of rare
      nonsynonymous allele load remained significant. Overall, we did not find clear
      support for mutational load burden on affection status; however, these results
      are ultimately dependent on and limited by the nature of the Genetic Analysis
      Workshop 17 simulation.

PMID- 22373139
TI  - High cell density growth of High Five suspension cells in DO-controlled wave
      mixed bioreactors.

PMID- 22373142
TI  - A method for metabolomic sampling of suspended animal cells using fast
      filtration.

PMID- 22373144
TI  - Integrating binary traits with quantitative phenotypes for association mapping of
      multivariate phenotypes.
AB  - Clinical binary end-point traits are often governed by quantitative precursors.
      Hence it may be a prudent strategy to analyze a clinical end-point trait by
      considering a multivariate phenotype vector, possibly including both quantitative
      and qualitative phenotypes. A major statistical challenge lies in integrating the
      constituent phenotypes into a reduced univariate phenotype for association
      analyses. We assess the performances of certain reduced phenotypes using analysis
      of variance and a model-free quantile-based approach. We find that analysis of
      variance is more powerful than the quantile-based approach in detecting
      association, particularly for rare variants. We also find that using a principal
      component of the quantitative phenotypes and the residual of a logistic
      regression of the binary phenotype on the quantitative phenotypes may be an
      optimal method for integrating a binary phenotype with quantitative phenotypes to
      define a reduced univariate phenotype.

PMID- 22373145
TI  - In-situ microscopy and 2D fluorescence spectroscopy as online methods for
      monitoring CHO cells during cultivation.

PMID- 22373146
TI  - Are quantitative trait-dependent sampling designs cost-effective for analysis of
      rare and common variants?
AB  - Use of trait-dependent sampling designs in whole-genome association studies of
      sequence data can reduce total sequencing costs with modest losses of statistical
      efficiency. In a quantitative trait (QT) analysis of data from the Genetic
      Analysis Workshop 17 mini-exome for unrelated individuals in the Asian
      subpopulation, we investigate alternative designs that sequence only 50% of the
      entire cohort. In addition to a simple random sampling design, we consider
      extreme-phenotype designs that are of increasing interest in genetic association
      analysis of QTs, especially in studies concerned with the detection of rare
      genetic variants. We also evaluate a novel sampling design in which all
      individuals have a nonzero probability of being selected into the sample but in
      which individuals with extreme phenotypes have a proportionately larger
      probability. We take differential sampling of individuals with informative trait
      values into account by inverse probability weighting using standard survey
      methods which thus generalizes to the source population. In replicate 1 data, we
      applied the designs in association analysis of Q1 with both rare and common
      variants in the FLT1 gene, based on knowledge of the generating model. Using all
      200 replicate data sets, we similarly analyzed Q1 and Q4 (which is known to be
      free of association with FLT1) to evaluate relative efficiency, type I error, and
      power. Simulation study results suggest that the QT-dependent selection designs
      generally yield greater than 50% relative efficiency compared to using the entire
      cohort, implying cost-effectiveness of 50% sample selection and worthwhile
      reduction of sequencing costs.

PMID- 22373147
TI  - Applications of nanoparticels in molecular and cellular biology and cancer
      research.

PMID- 22373148
TI  - New reporter cell clones to determine the biological activity of human type I
      interferons.

PMID- 22373150
TI  - Towards mainstreaming of biodiversity data publishing: recommendations of the
      GBIF Data Publishing Framework Task Group.
AB  - BACKGROUND: Data are the evidentiary basis for scientific hypotheses, analyses
      and publication, for policy formation and for decision-making. They are essential
      to the evaluation and testing of results by peer scientists both present and
      future. There is broad consensus in the scientific and conservation communities
      that data should be freely, openly available in a sustained, persistent and
      secure way, and thus standards for 'free' and 'open' access to data have become
      well developed in recent years. The question of effective access to data remains
      highly problematic. DISCUSSION: Specifically with respect to scientific
      publishing, the ability to critically evaluate a published scientific hypothesis
      or scientific report is contingent on the examination, analysis, evaluation - and
      if feasible - on the re-generation of data on which conclusions are based. It is
      not coincidental that in the recent 'climategate' controversies, the quality and
      integrity of data and their analytical treatment were central to the debate.
      There is recent evidence that even when scientific data are requested for
      evaluation they may not be available. The history of dissemination of scientific
      results has been marked by paradigm shifts driven by the emergence of new
      technologies. In recent decades, the advance of computer-based technology linked
      to global communications networks has created the potential for broader and more
      consistent dissemination of scientific information and data. Yet, in this digital
      era, scientists and conservationists, organizations and institutions have often
      been slow to make data available. Community studies suggest that the withholding
      of data can be attributed to a lack of awareness, to a lack of technical
      capacity, to concerns that data should be withheld for reasons of perceived
      personal or organizational self interest, or to lack of adequate mechanisms for
      attribution. CONCLUSIONS: There is a clear need for institutionalization of a
      'data publishing framework' that can address sociocultural, technical
      infrastructural, policy, political and legal constraints, as well as addressing
      issues of sustainability and financial support. To address these aspects of a
      data publishing framework - a systematic, standard approach to the formal
      definition and public disclosure of data - in the context of biodiversity data,
      the Global Biodiversity Information Facility (GBIF, the single inter-governmental
      body most clearly mandated to undertake such an effort) convened a Data
      Publishing Framework Task Group. We conceive this data publishing framework as an
      environment conducive to ensure free and open access to world's biodiversity
      data. Here, we present the recommendations of that Task Group, which are intended
      to encourage free and open access to the worlds' biodiversity data.

PMID- 22373151
TI  - ATF4 over-expression increased IgG1 productivity in Chinese hamster ovary cells.

PMID- 22373152
TI  - Improvement of insulin resistance by Cyanidin 3-glucoside, anthocyanin from black
      beans through the up-regulation of GLUT4 gene expression.

PMID- 22373155
TI  - Genetic Analysis Workshop 17 mini-exome simulation.
AB  - The data set simulated for Genetic Analysis Workshop 17 was designed to mimic a
      subset of data that might be produced in a full exome screen for a complex
      disorder and related risk factors in order to permit workshop participants to
      investigate issues of study design and statistical genetic analysis. Real
      sequence data from the 1000 Genomes Project formed the basis for simulating a
      common disease trait with a prevalence of 30% and three related quantitative risk
      factors in a sample of 697 unrelated individuals and a second sample of 697
      individuals in large, extended pedigrees. Called genotypes for 24,487 autosomal
      markers assigned to 3,205 genes and simulated affection status, quantitative
      traits, age, sex, pedigree relationships, and cigarette smoking were provided to
      workshop participants. The simulating model included both common and rare
      variants with minor allele frequencies ranging from 0.07% to 25.8% and a wide
      range of effect sizes for these variants. Genotype-smoking interaction effects
      were included for variants in one gene. Functional variants were concentrated in
      genes selected from specific biological pathways and were selected on the basis
      of the predicted deleteriousness of the coding change. For each sample, unrelated
      individuals and family, 200 replicates of the phenotypes were simulated.

PMID- 22373153
TI  - Structure-based and ligand-based virtual screening of novel methyltransferase
      inhibitors of the dengue virus.
AB  - BACKGROUND: The dengue virus is the most significant arthropod-borne human
      pathogen, and an increasing number of cases have been reported over the last few
      decades. Currently neither vaccines nor drugs against the dengue virus are
      available. NS5 methyltransferase (MTase), which is located on the surface of the
      dengue virus and assists in viral attachment to the host cell, is a promising
      antiviral target. In order to search for novel inhibitors of NS5 MTase, we
      performed a computer-aided virtual screening of more than 5 million commercially
      available chemical compounds using two approaches: i) structure-based screening
      using the crystal structure of NS5 MTase and ii) ligand-based screening using
      active ligands of NS5 MTase. Structure-based screening was performed using the
      LIDAEUS (LIgand Discovery At Edinburgh UniverSity) program. The ligand-based
      screening was carried out using the EDULISS (EDinburgh University LIgand
      Selection System) program. RESULTS: The selection of potential inhibitors of
      dengue NS5 MTase was based on two criteria: the compounds must bind to NS5 MTase
      with a higher affinity than that of active NS5 MTase ligands, such as ribavirin
      triphosphate (RTP) and S-adenosyl-L-homocysteine (SAH); and the compounds must
      interact with residues that are catalytically important for the function of NS5
      MTase. We found several compounds that bind strongly to the RNA cap site and the
      S-adenosyl-L-methionine (SAM) binding site of NS5 MTase with better binding
      affinities than that of RTP and SAH. We analyzed the mode of binding for each
      compound to its binding site, and our results suggest that all compounds bind to
      their respective binding sites by interacting with, and thus blocking, residues
      that are vital for maintaining the catalytic activity of NS5 MTase. CONCLUSIONS:
      We discovered several potential compounds that are active against dengue virus
      NS5 MTase through virtual screening using structure-based and ligand-based
      methods. These compounds were predicted to bind into the SAM binding site and the
      RNA cap site with higher affinities than SAH and RTP. These compounds are
      commercially available and can be purchased for further biological activity
      tests.

PMID- 22373157
TI  - LDH-C can be differentially expressed during fermentation of CHO cells.
AB  - Expression of CHO mRNA was measured with special microarrays from the Consortium
      for Chinese Hamster Ovary (CHO) Cell Genomics led by Prof. Wei-Shou Hu of the
      University of Minnesota and Prof. Miranda Yap of the Bioprocess Technology
      Institute of A*STAR, Singapore (http://hugroup.cems.umn.edu/CHO/cho_index.html).
      Cultivation experiments were performed in small scale 2L stirred tank
      bioreactors. During fermentation a temperature shift of -3 degrees C was
      performed. This was accompanied by a reduction of the cell specific lactate
      production rate. The analysis of transcriptome samples before and after the
      temperature shift with microarrays showed several changes in the expression of
      available gene markers. LDH-C expression raised about 2 fold after temperature
      shift. LDH-A did not change. As LDH-C is known to be a specialized isoenzyme in
      sperm cells for consuming lactate in a lactate containing milieu, LDH-C could be
      proposed as a target for genetic engineering, facilitating lactate consumption in
      the late phase of high cell density cultures and prolonging longevity of CHO
      production cultures by reducing lactate and base accumulation. 

PMID- 22373158
TI  - Penalized-regression-based multimarker genotype analysis of Genetic Analysis
      Workshop 17 data.
AB  - Testing for association between multiple markers and a phenotype can not only
      capture untyped causal variants in weak linkage disequilibrium with nearby typed
      markers but also identify the effect of a combination of markers. We propose a
      sliding window approach that uses multimarker genotypes as variables in a
      penalized regression. We investigate a penalty with three separate components:
      (1) a group least absolute shrinkage and selection operator (LASSO) that selects
      multimarker genotypes in a gene to be included in or excluded from the model, (2)
      an allele-sharing penalty that encourages multimarker genotypes with similar
      alleles to have similar coefficients, and (3) a penalty that shrinks the size of
      coefficients while performing model selection. The penalized likelihood is
      minimized with a cyclic coordinate descent algorithm, allowing quick coefficient
      estimation for a large number of markers. We compare our method to single-marker
      analysis and a gene-based sparse group LASSO on the Genetic Analysis Workshop 17
      data for quantitative trait Q2. We found that all of the methods were
      underpowered to detect the simulated rare causal variants at the low false
      positive rates desired in association studies. However, the sparse group LASSO on
      multi-marker genotypes seems to provide some advantage over the sparse group
      LASSO applied to single SNPs within genes, giving further evidence that there may
      be an advantage to modeling combinations of rare variant alleles over modeling
      them individually.

PMID- 22373159
TI  - Using a single question to assess physical activity in older adults: a
      reliability and validity study.
AB  - BACKGROUND: Single-item physical activity questions provide a quick approximation
      of physical activity levels. While recall questionnaires provide a more detailed
      picture of an individual's level of physical activity, single-item questions may
      be more appropriate in certain situations. The aim of this study was to evaluate
      two single-item physical activity questions (one absolute question and one
      relative question) for test-retest reliability, convergent validity, and
      discriminant validity, in a sample of older adults. METHODS: Data was obtained
      from the Project to Prevent Falls in Veterans, a fall risk-factor screening and
      modification trial. One question measured absolute physical activity (seldom,
      moderately, vigorously active) and one measured relative physical activity (more,
      about as, less active than peers). Test-retest reliability was examined using
      weighted Kappa statistics (kappa) in a sample of 43 subjects. Validity was
      assessed using correlation coefficients (r) in participants who received clinical
      assessments (n = 159). RESULTS: The absolute physical activity question was more
      reliable than the relative physical activity question (kappa = 0.75 vs. kappa =
      0.56). Convergent validity, however, was stronger for the relative physical
      activity question (r = 0.28 to 0.57 vs. r = 0.10 to 0.33). Discriminant validity
      was similar for both questions. For the relative physical activity question,
      there was moderate agreement when this question was re-administered seven days
      later, fair to moderate/good associations when compared with indicators of
      physical function, and little to no associations when compared with measures
      hypothesized to be theoretically not related to physical activity. CONCLUSIONS:
      The relative physical activity question had the best combination of test-retest
      reliability, convergent validity and discriminant validity. In studies requiring
      a measure of physical activity, where physical activity is not the primary focus
      and more detailed measures are not feasible, a single question may be an
      acceptable alternative.

PMID- 22373162
TI  - Joint association analysis of bivariate quantitative and qualitative traits.
AB  - Univariate genome-wide association analysis of quantitative and qualitative
      traits has been investigated extensively in the literature. In the presence of
      correlated phenotypes, it is more intuitive to analyze all phenotypes
      simultaneously. We describe an efficient likelihood-based approach for the joint
      association analysis of quantitative and qualitative traits in unrelated
      individuals. We assume a probit model for the qualitative trait, under which an
      unobserved latent variable and a prespecified threshold determine the value of
      the qualitative trait. To jointly model the quantitative and qualitative traits,
      we assume that the quantitative trait and the latent variable follow a bivariate
      normal distribution. The latent variable is allowed to be correlated with the
      quantitative phenotype. Simultaneous modeling of the quantitative and qualitative
      traits allows us to make more precise inference on the pleiotropic genetic
      effects. We derive likelihood ratio tests for the testing of genetic effects. An
      application to the Genetic Analysis Workshop 17 data is provided. The new method
      yields reasonable power and meaningful results for the joint association analysis
      of the quantitative trait Q1 and the qualitative trait disease status at SNPs
      with not too small MAF.

PMID- 22373163
TI  - Analysis of glycolytic flux as a rapid screen to identify low lactate producing
      CHO cell lines with desirable monoclonal antibody yield and glycan profile.

PMID- 22373164
TI  - Identification of functional rare variants in genome-wide association studies
      using stability selection based on random collapsing.
AB  - Genome-wide association studies are a powerful approach used to identify common
      variants for complex disease. However, the traditional genome-wide association
      methods may not be optimal when they are applied to rare variants because of the
      rare variants' low frequencies and weak signals. To alleviate the difficulty,
      investigators have proposed many methods that collapse rare variants. In this
      paper, we propose a novel ranking method, which we call stability selection based
      on random collapsing, to rank the candidate rare variants. We use the simulated
      mini-exome data sets of unrelated individuals from Genetic Analysis Workshop 17
      for the analysis. The numerical results suggest that the selection based on a
      random collapsing method is promising for identifying functional rare variants in
      genome-wide association studies. Further research to examine the error control
      property of the proposed method is underway.

PMID- 22373165
TI  - Rare variant density across the genome and across populations.
AB  - Next-generation sequencing allows for a new focus on rare variant density for
      conducting analyses of association to disease and for narrowing down the genomic
      regions that show evidence of functionality. In this study we use the 1000
      Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to
      compare rare variant densities across seven populations. We made the comparisons
      using regressions of rare variants on total variant counts per gene for each
      population and Tajima's D values calculated for each gene in each population,
      using data on 3,205 genes. We found that the populations clustered by continent
      for both the regression slopes and Tajima's D values, with the African
      populations (Yoruba and Luhya) showing the highest density of rare variants,
      followed by the Asian populations (Han and Denver Chinese followed by the
      Japanese) and the European populations (CEPH [European-descent] and Tuscan) with
      the lowest densities. These significant differences in rare variant densities
      across populations seem to translate to measures of the rare variant density more
      commonly used in rare variant association analyses, suggesting the need to adjust
      for ancestry in such analyses. The selection signal was high for AHNAK, HLA-A,
      RANBP2, and RGPD4, among others. RANBP2 and RGPD4 showed a marked difference in
      rare variant density and potential selection between the Luhya and the other
      populations. This may suggest that differences between populations should be
      considered when delimiting genomic regions according to functionality and that
      these differences can create potential for disease heterogeneity.

PMID- 22373166
TI  - Bag-based rapid and safe seed-train expansion method for Trichoplusia ni
      suspension cells.

PMID- 22373168
TI  - 2D and 3D-QSAR study on 4-anilinoquinozaline derivatives as potent apoptosis
      inducer and efficacious anticancer agent.
AB  - BACKGROUND: Apoptosis is known as programmed cell death that plays an important
      role in tumor biology. METHODS: In this study, apoptosis-inducing activity is
      predicted by using a QSAR modeling approach for a series of 4-anilinoquinozaline
      derivatives. 2D-QSAR model for the prediction of apoptosis-inducing activity was
      obtained by applying multiple linear regression giving r2 = 0.8225 and q2 =
      0.7626, principal component regression giving r2 = 0.7539 and q2 = 0.6669 and
      partial least squares giving r2 = 0.8237 and q2 = 0.6224. RESULTS: QSAR study
      revealed that alignment-independent descriptors and distance-based topology index
      are the most important descriptors in predicting apoptosis-inducing activity. 3D
      QSAR study was performed using k-nearest neighbor molecular field analysis (kNN
      MFA) approach for both electrostatic and steric fields. Three different kNN-MFA
      3D-QSAR methods (SW-FB, SA, and GA) were used for the development of models and
      tested successfully for internal (q2 > 0.62) and external (predictive r2 > 0.52)
      validation criteria. Thus, 3D-QSAR models showed that electrostatic effects
      dominantly determine the binding affinities. CONCLUSIONS: The QSAR models
      developed in this study would be useful for the development of new apoptosis
      inducer as anticancer agents.

PMID- 22373173
TI  - Stem cell: from basic theoretical assumptions and mathematical concepts to the
      computational models.

PMID- 22373170
TI  - Used glasses versus ready-made spectacles for the treatment of refractive error.
AB  - BACKGROUND AND OBJECTIVE: To compare visual outcomes for used glasses versus
      ready-made spectacles in the treatment of refractive error. PATIENTS AND METHODS:
      In this prospective, comparative case series, undilated refractive error
      screening examinations were conducted over a 5-week period. Patients with
      bilateral refractive error were treated with used glasses and ready-made
      spectacles powered to match their prescriptions. Snellen visual acuity was
      measured with no correction, best (manifest) correction, unrefined
      autorefraction, used glasses, and ready-made spectacles. Main outcome
      measurements were the mean visual improvement from uncorrected acuity and median
      final visual acuity after treatment with used and ready-made spectacles. RESULTS:
      One hundred forty-one patients ages 18 and older with bilateral refractive error
      were examined. Uncorrected visual acuity in each eye improved an average of 4.5
      lines with best correction, 4.0 lines with used glasses, and 3.5 lines with ready
      made spectacles, with used glasses demonstrating a statistically significant
      advantage over ready-made spectacles (P < .001). The median visual acuity in the
      better eye improved from 20/60 uncorrected to 20/25 with all types of glasses. In
      patients with less than 1 diopter of anisometropia and greater than 1 diopter of
      astigmatism in each eye (49%), the ready-made spectacles performed equally as
      well as the used glasses (P = .95), improving vision an average of 3.9 lines for
      a median final visual acuity of 20/25 in the better eye. CONCLUSION: Although
      both were effective, used glasses are better than ready-made spectacles for
      improving vision loss due to refractive error.

PMID- 22373171
TI  - On-line and real time cell counting and viability determination for animal cell
      process monitoring by in situ microscopy.

PMID- 22373174
TI  - A platform fed-batch process for various CEMAX((r)) producer cell lines.

PMID- 22373175
TI  - The data paper: a mechanism to incentivize data  publishing in biodiversity
      science.
AB  - BACKGROUND: Free and open access to primary biodiversity data is essential for
      informed decision-making to achieve conservation of biodiversity and sustainable
      development. However, primary biodiversity data are neither easily accessible nor
      discoverable. Among several impediments, one is a lack of incentives to data
      publishers for publishing of their data resources. One such mechanism currently
      lacking is recognition through conventional scholarly publication of enriched
      metadata, which should ensure rapid discovery of 'fit-for-use' biodiversity data
      resources. DISCUSSION: We review the state of the art of data discovery options
      and the mechanisms in place for incentivizing data publishers efforts towards
      easy, efficient and enhanced publishing, dissemination, sharing and re-use of
      biodiversity data. We propose the establishment of the 'biodiversity data paper'
      as one possible mechanism to offer scholarly recognition for efforts and
      investment by data publishers in authoring rich metadata and publishing them as
      citable academic papers. While detailing the benefits to data publishers, we
      describe the objectives, work flow and outcomes of the pilot project commissioned
      by the Global Biodiversity Information Facility in collaboration with scholarly
      publishers and pioneered by Pensoft Publishers through its journals Zookeys,
      PhytoKeys, MycoKeys, BioRisk, NeoBiota, Nature Conservation and the forthcoming
      Biodiversity Data Journal. We then debate further enhancements of the data paper
      beyond the pilot project and attempt to forecast the future uptake of data papers
      as an incentivization mechanism by the stakeholder communities. CONCLUSIONS: We
      believe that in addition to recognition for those involved in the data publishing
      enterprise, data papers will also expedite publishing of fit-for-use biodiversity
      data resources. However, uptake and establishment of the data paper as a
      potential mechanism of scholarly recognition requires a high degree of commitment
      and investment by the cross-sectional stakeholder communities.

PMID- 22373176
TI  - Engineering CHO cell growth by stable manipulation of miRNA expression.

PMID- 22373178
TI  - Incorporating predicted functions of nonsynonymous variants into gene-based
      analysis of exome sequencing data: a comparative study.
AB  - Next-generation sequencing has opened up new avenues for the genetic study of
      complex traits. However, because of the small number of observations for any
      given rare allele and high sequencing error, it is a challenge to identify
      functional rare variants associated with the phenotype of interest. Recent
      research shows that grouping variants by gene and incorporating computationally
      predicted functions of variants may provide higher statistical power. On the
      other hand, many algorithms are available for predicting the damaging effects of
      nonsynonymous variants. Here, we use the simulated mini-exome data of Genetic
      Analysis Workshop 17 to study and compare the effects of incorporating the
      functional predictions of single-nucleotide polymorphisms using two popular
      algorithms, SIFT and PolyPhen-2, into a gene-based association test. We also
      propose a simple mixture model that can effectively combine test results based on
      different functional prediction algorithms.

PMID- 22373179
TI  - Measurement of sialic acid content on recombinant membrane proteins.

PMID- 22373180
TI  - Analysis of human mini-exome sequencing data from Genetic Analysis Workshop 17
      using a Bayesian hierarchical mixture model.
AB  - Next-generation sequencing technologies are rapidly changing the field of genetic
      epidemiology and enabling exploration of the full allele frequency spectrum
      underlying complex diseases. Although sequencing technologies have shifted our
      focus toward rare genetic variants, statistical methods traditionally used in
      genetic association studies are inadequate for estimating effects of low minor
      allele frequency variants. Four our study we use the Genetic Analysis Workshop 17
      data from 697 unrelated individuals (genotypes for 24,487 autosomal variants from
      3,205 genes). We apply a Bayesian hierarchical mixture model to identify genes
      associated with a simulated binary phenotype using a transformed genotype design
      matrix weighted by allele frequencies. A Metropolis Hasting algorithm is used to
      jointly sample each indicator variable and additive genetic effect pair from its
      conditional posterior distribution, and remaining parameters are sampled by Gibbs
      sampling. This method identified 58 genes with a posterior probability greater
      than 0.8 for being associated with the phenotype. One of these 58 genes, PIK3C2B
      was correctly identified as being associated with affected status based on the
      simulation process. This project demonstrates the utility of Bayesian
      hierarchical mixture models using a transformed genotype matrix to detect genes
      containing rare and common variants associated with a binary phenotype.

PMID- 22373181
TI  - Application of Bayesian regression with singular value decomposition method in
      association studies for sequence data.
AB  - Genetic association studies usually involve a large number of single-nucleotide
      polymorphisms (SNPs) (k) and a relative small sample size (n), which produces the
      situation that k is much greater than n. Because conventional statistical
      approaches are unable to deal with multiple SNPs simultaneously when k is much
      greater than n, single-SNP association studies have been used to identify genes
      involved in a disease's pathophysiology, which causes a multiple testing problem.
      To evaluate the contribution of multiple SNPs simultaneously to disease traits
      when k is much greater than n, we developed the Bayesian regression with singular
      value decomposition (BRSVD) method. The method reduces the dimension of the
      design matrix from k to n by applying singular value decomposition to the design
      matrix. We evaluated the model using a Markov chain Monte Carlo simulation with
      Gibbs sampler constructed from the posterior densities driven by conjugate prior
      densities. Permutation was incorporated to generate empirical p-values. We
      applied the BRSVD method to the sequence data provided by Genetic Analysis
      Workshop 17 and found that the BRSVD method is a practical method that can be
      used to analyze sequence data in comparison to the single-SNP association test
      and the penalized regression method.

PMID- 22373183
TI  - Identification of genes and variants associated with quantitative traits using
      Bayesian factor screening.
AB  - We propose a factor-screening method based on a Bayesian model selection
      framework and apply it to Genetic Analysis Workshop 17 simulated data with
      unrelated individuals to identify genes and SNP variants associated with the
      quantitative trait Q1. A Metropolis-Hasting algorithm is implemented to generate
      a posterior distribution in a restricted model space and thus the marginal
      posterior distribution of each variant. Our framework provides flexibility to
      make inferences on either individual variants or genes. We obtained results for
      10 simulated data sets. Our methods are able to identify FTP1 and KDR, two genes
      that are associated with Q1 in a majority of replicates.

PMID- 22373182
TI  - Risk factors and a predictive model for under-five mortality in Nigeria: evidence
      from Nigeria demographic and health survey.
AB  - BACKGROUND: Under-5 mortality is a major public health challenge in developing
      countries. It is essential to identify determinants of under-five mortality (U5M)
      childhood mortality because these will assist in formulating appropriate health
      programmes and policies in order to meet the United Nations MDG goal. The
      objective of this study was to develop a predictive model and identify maternal,
      child, family and other risk factors associated U5M in Nigeria. METHODS:
      Population-based cross-sectional study which explored 2008 demographic and health
      survey of Nigeria (NDHS) with multivariable logistic regression. Likelihood Ratio
      Test, Hosmer-Lemeshow Goodness-of-Fit and Variance Inflation Factor were used to
      check the fit of the model and the predictive power of the model was assessed
      with Receiver Operating Curve (ROC curve). RESULTS: This study yielded an
      excellent predictive model which revealed that the likelihood of U5M among the
      children of mothers that had their first marriage at age 20-24 years and >=25
      years declined by 20% and 30% respectively compared to children of those that
      married before the age of 15 years. Also, the following factors reduced odds of
      U5M: health seeking behaviour, breastfeeding children for >18 months, use of
      contraception, small family size, having one wife, low birth order, normal birth
      weight, child spacing, living in urban areas, and good sanitation. CONCLUSIONS:
      This study has revealed that maternal, child, family and other factors were
      important risk factors of U5M in Nigeria. This study has identified important
      risk factors that will assist in formulating policies that will improve child
      survival.

PMID- 22373185
TI  - In silico approach to screen compounds active against parasitic nematodes of
      major socio-economic importance.
AB  - BACKGROUND: Infections due to parasitic nematodes are common causes of morbidity
      and fatality around the world especially in developing nations. At present
      however, there are only three major classes of drugs for treating human nematode
      infections. Additionally the scientific knowledge on the mechanism of action and
      the reason for the resistance to these drugs is poorly understood. Commercial
      incentives to design drugs that are endemic to developing countries are limited
      therefore, virtual screening in academic settings can play a vital role is
      discovering novel drugs useful against neglected diseases. In this study we
      propose to build robust machine learning model to classify and screen compounds
      active against parasitic nematodes. RESULTS: A set of compounds active against
      parasitic nematodes were collated from various literature sources including
      PubChem while the inactive set was derived from DrugBank database. The support
      vector machine (SVM) algorithm was used for model development, and stratified ten
      fold cross validation was used to evaluate the performance of each classifier.
      The best results were obtained using the radial basis function kernel. The SVM
      method achieved an accuracy of 81.79% on an independent test set. Using the model
      developed above, we were able to indentify novel compounds with potential
      anthelmintic activity. CONCLUSION: In this study, we successfully present the SVM
      approach for predicting compounds active against parasitic nematodes which
      suggests the effectiveness of computational approaches for antiparasitic drug
      discovery. Although, the accuracy obtained is lower than the previously reported
      in a similar study but we believe that our model is more robust because we
      intentionally employed stringent criteria to select inactive dataset thus making
      it difficult for the model to classify compounds. The method presents an
      alternative approach to the existing traditional methods and may be useful for
      predicting hitherto novel anthelmintic compounds.

PMID- 22373186
TI  - Influence of cell specific productivity on product quality.

PMID- 22373187
TI  - Characterization of novel pneumatic mixing for single-use bioreactor application.

PMID- 22373188
TI  - Detection of rare variant effects in association studies: extreme values,
      iterative regression, and a hybrid approach.
AB  - We develop statistical methods for detecting rare variants that are associated
      with quantitative traits. We propose two strategies and their combination for
      this purpose: the iterative regression strategy and the extreme values strategy.
      In the iterative regression strategy, we use iterative regression on residuals
      and a multimarker association test to identify a group of significant variants.
      In the extreme values strategy, we use individuals with extreme trait values to
      select candidate genes and then test only these candidate genes. These two
      strategies are integrated into a hybrid approach through a weighting technology.
      We apply the proposed methods to analyze the Genetic Analysis Workshop 17 data
      set. The results show that the hybrid approach is the most powerful approach.
      Using the hybrid approach, the average power to detect causal genes for Q1 is
      about 40% and the powers to detect FLT1 and KDR are 100% and 68% for Q1,
      respectively. The powers to detect VNN3 and BCHE are 34% and 30% for Q2,
      respectively.

PMID- 22373189
TI  - Gene-based multiple trait analysis for exome sequencing data.
AB  - The common genetic variants identified through genome-wide association studies
      explain only a small proportion of the genetic risk for complex diseases. The
      advancement of next-generation sequencing technologies has enabled the detection
      of rare variants that are expected to contribute significantly to the missing
      heritability. Some genetic association studies provide multiple correlated traits
      for analysis. Multiple trait analysis has the potential to improve the power to
      detect pleiotropic genetic variants that influence multiple traits. We propose a
      gene-level association test for multiple traits that accounts for correlation
      among the traits. Gene- or region-level testing for association involves both
      common and rare variants. Statistical tests for common variants may have limited
      power for individual rare variants because of their low frequency and multiple
      testing issues. To address these concerns, we use the weighted-sum pooling method
      to test the joint association of multiple rare and common variants within a gene.
      The proposed method is applied to the Genetic Association Workshop 17 (GAW17)
      simulated mini-exome data to analyze multiple traits. Because of the nature of
      the GAW17 simulation model, increased power was not observed for multiple-trait
      analysis compared to single-trait analysis. However, multiple-trait analysis did
      not result in a substantial loss of power because of the testing of multiple
      traits. We conclude that this method would be useful for identifying pleiotropic
      genes.

PMID- 22373191
TI  - A bioactive flavonoid from Pavetta crassipes K. Schum.
AB  - BACKGROUND: In our continued search for bioactive compounds from plants,
      conscious effort is being made to rapidly analyze ethnobotanical plants used for
      treating various ailments by traditional healers before this information is
      irrevocably lost as societies advance and rural communities become urbanized.
      RESULTS: A compound isolated from the aqueous extract of Pavetta crassipes leaves
      showed activity against some pathogenic microorganisms which included
      Streptococcus pyogenes, Corynebacterium ulcerans, Klebsiella pneumoniae,
      Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Escherichia coli at a
      concentration < 50 mg/mL. The compound had minimum inhibitory concentration
      ranging from 6.25 to 12.5 mg/mL and minimum bactericidal concentration ranging
      from 12.5 to 25 mg/mL. The compound was identified using 1D and 2D NMR
      experiments and comparison with literature data as quercetin-3-O-rutinoside.
      CONCLUSIONS: This has supported the ethnomedicinal use of the plant, confirmed
      its activity, and has also provided an easy and simple method for isolating this
      compound which has a lot of pharmaceutical and cosmetic applications from a new
      source.

PMID- 22373192
TI  - On-line monitoring of the live cell concentration in bioreactors based on a
      rocking platform.

PMID- 22373195
TI  - Expression of recombinant human coagulation factors VII (rFVII) and IX (rFIX) in
      various cell types, glycosylation analysis, and pharmacokinetic comparison.

PMID- 22373196
TI  - Characterization of the human AGE1.HN cell line: a systems biology approach.

PMID- 22373197
TI  - Development of a chemically defined CHO medium by engineering based on a feed
      solution.

PMID- 22373200
TI  - Indicators for the Data Usage Index (DUI): an  incentive for publishing primary
      biodiversity data  through global information infrastructure.
AB  - BACKGROUND: A professional recognition mechanism is required to encourage
      expedited publishing of an adequate volume of 'fit-for-use' biodiversity data. As
      a component of such a recognition mechanism, we propose the development of the
      Data Usage Index (DUI) to demonstrate to data publishers that their efforts of
      creating biodiversity datasets have impact by being accessed and used by a wide
      spectrum of user communities. DISCUSSION: We propose and give examples of a range
      of 14 absolute and normalized biodiversity dataset usage indicators for the
      development of a DUI based on search events and dataset download instances. The
      DUI is proposed to include relative as well as species profile weighted
      comparative indicators. CONCLUSIONS: We believe that in addition to the
      recognition to the data publisher and all players involved in the data life
      cycle, a DUI will also provide much needed yet novel insight into how users use
      primary biodiversity data. A DUI consisting of a range of usage indicators
      obtained from the GBIF network and other relevant access points is within reach.
      The usage of biodiversity datasets leads to the development of a family of
      indicators in line with well known citation-based measurements of recognition.

PMID- 22373201
TI  - Comparison of the activity and pluripotency maintaining potential of human
      leukemia inhibitory factor (LIF) produced in E.coli and CHO cells.

PMID- 22373202
TI  - Toric implantable collamer lens implantation in a case with bilateral primary
      peripheral iris cysts.
AB  - The authors describe a patient who was found to have bilateral, peripheral iris
      cysts during preoperative ultrasound biomicroscopy (UBM) assessment prior to
      toric implantable collamer lens (TICL) implantation. TICL implantation was
      undertaken with no intraoperative or postoperative complications. The TICLs
      remained in stable position over a follow-up period of 15 months. The presence of
      solitary temporal iris cysts had no impact on final visual outcome or TICL
      position.

PMID- 22373203
TI  - Rare variant collapsing in conjunction with mean log p-value and gradient
      boosting approaches applied to Genetic Analysis Workshop 17 data.
AB  - In addition to methods that can identify common variants associated with
      susceptibility to common diseases, there has been increasing interest in
      approaches that can identify rare genetic variants. We use the simulated data
      provided to the participants of Genetic Analysis Workshop 17 (GAW17) to identify
      both rare and common single-nucleotide polymorphisms and pathways associated with
      disease status. We apply a rare variant collapsing approach and the usual
      association tests for common variants to identify candidates for further analysis
      using pathway-based and tree-based ensemble approaches. We use the mean log p
      value approach to identify a top set of pathways and compare it to those used in
      simulation of GAW17 dataset. We conclude that the mean log p-value approach is
      able to identify those pathways in the top list and also related pathways. We
      also use the stochastic gradient boosting approach for the selected subset of
      single-nucleotide polymorphisms. When compared the result of this tree-based
      method with the list of single-nucleotide polymorphisms used in dataset
      simulation, in addition to correct SNPs we observe number of false positives.

PMID- 22373204
TI  - Identifying causal rare variants of disease through family-based analysis of
      Genetics Analysis Workshop 17 data set.
AB  - Linkage- and association-based methods have been proposed for mapping disease
      causing rare variants. Based on the family information provided in the Genetic
      Analysis Workshop 17 data set, we formulate a two-pronged approach that combines
      both methods. Using the identity-by-descent information provided for eight
      extended pedigrees (n = 697) and the simulated quantitative trait Q1, we explore
      various traditional nonparametric linkage analysis methods; the best result is
      obtained by assuming between-family heterogeneity and applying the Haseman-Elston
      regression to each pedigree separately. We discover strong signals from two genes
      in two different families and weaker signals for a third gene from two other
      families. As an exploratory approach, we apply an association test based on a
      modified family-based association test statistic to all rare variants (frequency
      < 1% or < 3%) designated as causal for Q1. Family-based association tests
      correctly identified causal single-nucleotide polymorphisms for four genes (KDR,
      VEGFA, VEGFC, and FLT1). Our results suggest that both linkage and association
      tests with families show promise for identifying rare variants.

PMID- 22373206
TI  - Confidence set of putative quantitative trait loci in whole genome scans with
      application to the Genetic Analysis Workshop 17 simulated data.
AB  - As genetic maps become more highly dense, the ability to sufficiently localize
      putative disease loci becomes an achievable goal. This has prompted an increased
      interest in methods for constructing confidence intervals for the location of
      variants that contribute to a trait. Such intervals are important because, by
      reducing the number of candidate loci, they can help in the design of cost
      effective and time-efficient follow-up studies. We introduce a new approach that
      can be used in whole-genome scans to obtain a confidence set of loci that
      contribute at least a predetermined percentage h to the overall genetic variation
      of a quantitative phenotype. The method is developed in the framework of
      generalized linear mixed models and can accommodate families of arbitrary size
      and structure. We apply our method to the Genetic Analysis Workshop 17 simulated
      data where we scan chromosomes 6, 15, 20, 21, and 22 to uncover loci regulating
      the simulated phenotype Q2. For the analyses we had prior knowledge of the
      simulation model used to generate the phenotype.

PMID- 22373209
TI  - Comparison of statistical approaches to rare variant analysis for quantitative
      traits.
AB  - With recent advances in technology, deep sequencing data will be widely used to
      further the understanding of genetic influence on traits of interest. Therefore
      not only common variants but also rare variants need to be better used to exploit
      the new information provided by deep sequencing data. Recently, statistical
      approaches for analyzing rare variants in genetic association studies have been
      proposed, but many of them were designed only for dichotomous outcomes. We
      compare the type I error and power of several statistical approaches applicable
      to quantitative traits for collapsing and analyzing rare variant data within a
      defined gene region. In addition to comparing methods that consider only rare
      variants, such as indicator, count, and data-adaptive collapsing methods, we also
      compare methods that incorporate the analysis of common variants along with rare
      variants, such as CMC and LASSO regression. We find that the three methods used
      to collapse rare variants perform similarly in this simulation setting where all
      risk variants were simulated to have effects in the same direction. Further, we
      find that incorporating common variants is beneficial and using a LASSO
      regression to choose which common variants to include is most useful when there
      is are few common risk variants compared to the total number of risk variants.

PMID- 22373210
TI  - Prioritizing single-nucleotide variations that potentially regulate alternative
      splicing.
AB  - Recent evidence suggests that many complex diseases are caused by genetic
      variations that play regulatory roles in controlling gene expression. Most
      genetic studies focus on nonsynonymous variations that can alter the amino acid
      composition of a protein and are therefore believed to have the highest impact on
      phenotype. Synonymous variations, however, can also play important roles in
      disease pathogenesis by regulating pre-mRNA processing and translational control.
      In this study, we systematically survey the effects of single-nucleotide
      variations (SNVs) on binding affinity of RNA-binding proteins (RBPs). Among the
      10,113 synonymous SNVs identified in 697 individuals in the 1,000 Genomes Project
      and distributed by Genetic Analysis Workshop 17 (GAW17), we identified 182
      variations located in alternatively spliced exons that can significantly change
      the binding affinity of nine RBPs whose binding preferences on 7-mer RNA
      sequences were previously reported. We found that the minor allele frequencies of
      these variations are similar to those of nonsynonymous SNVs, suggesting that they
      are in fact functional. We propose a workflow to identify phenotype-associated
      regulatory SNVs that might affect alternative splicing from exome-sequencing
      derived genetic variations. Based on the affecting SNVs on the quantitative
      traits simulated in GAW17, we further identified two and four functional SNVs
      that are predicted to be involved in alternative splicing regulation in traits Q1
      and Q2, respectively.

PMID- 22373211
TI  - Enhanced protein synthesis and secretion using a rational signal-peptide library
      approach as a tailored tool.

PMID- 22373212
TI  - Next-generation sequencing of the CHO cell transcriptome.

PMID- 22373213
TI  - Identity-by-descent filtering as a tool for the identification of disease alleles
      in exome sequence data from distant relatives.
AB  - Large-scale, deep resequencing may be the next logical step in the genetic
      investigation of common complex diseases. Because each individual is likely to
      carry many thousands of variants, the identification of causal alleles requires
      an efficient strategy to reduce the number of candidate variants. Under many
      genetic models, causal alleles can be expected to reside within identity-by
      descent (IBD) regions shared by affected relatives. In distant relatives, IBD
      regions constitute a small portion of the genome and can thus greatly reduce the
      search space for causal alleles. However, the effectiveness of this strategy is
      unknown. We test the simulated mini-exome data set in extended pedigrees provided
      by Genetic Analysis Workshop 17. At the fourth- and fifth-degree level of
      relatedness, case-case pairs shared between 1% and 9% of the genome identical by
      descent. As expected, no genes were shared identical by descent by all case
      subjects, but 43 genes were shared by many case subjects across at least 50
      replicates. We filtered variants in these genes based on population frequency,
      function, informativeness, and evidence of association using the family-based
      association test. This analysis highlighted five genes previously implicated in
      triglyceride, lipid, and cholesterol metabolism. Comparison with the list of true
      risk alleles revealed that strict IBD filtering followed by association testing
      of the rarest alleles was the most sensitive strategy. IBD filtering may be a
      useful strategy for narrowing down the list of candidate variants in exome data,
      but the optimal degree of relatedness of affected pairs will depend on the
      genetic architecture of the disease under study.

PMID- 22373214
TI  - Building gene expression profile classifiers with a simple and efficient
      rejection option in R.
AB  - BACKGROUND: The collection of gene expression profiles from DNA microarrays and
      their analysis with pattern recognition algorithms is a powerful technology
      applied to several biological problems. Common pattern recognition systems
      classify samples assigning them to a set of known classes. However, in a clinical
      diagnostics setup, novel and unknown classes (new pathologies) may appear and one
      must be able to reject those samples that do not fit the trained model. The
      problem of implementing a rejection option in a multi-class classifier has not
      been widely addressed in the statistical literature. Gene expression profiles
      represent a critical case study since they suffer from the curse of
      dimensionality problem that negatively reflects on the reliability of both
      traditional rejection models and also more recent approaches such as one-class
      classifiers. RESULTS: This paper presents a set of empirical decision rules that
      can be used to implement a rejection option in a set of multi-class classifiers
      widely used for the analysis of gene expression profiles. In particular, we focus
      on the classifiers implemented in the R Language and Environment for Statistical
      Computing (R for short in the remaining of this paper). The main contribution of
      the proposed rules is their simplicity, which enables an easy integration with
      available data analysis environments. Since in the definition of a rejection
      model tuning of the involved parameters is often a complex and delicate task, in
      this paper we exploit an evolutionary strategy to automate this process. This
      allows the final user to maximize the rejection accuracy with minimum manual
      intervention. CONCLUSIONS: This paper shows how the use of simple decision rules
      can be used to help the use of complex machine learning algorithms in real
      experimental setups. The proposed approach is almost completely automated and
      therefore a good candidate for being integrated in data analysis flows in labs
      where the machine learning expertise required to tune traditional classifiers
      might not be available.

PMID- 22373215
TI  - Optimization of HEK 293 cell growth by addition of non-animal derived components
      using design of experiments.

PMID- 22373216
TI  - A novel peptide to enhance recombinant BMP-2 production in mammalian cell
      cultures.

PMID- 22373217
TI  - Synthesis of new pyrazolyl-2, 4-thiazolidinediones as antibacterial and
      antifungal agents.
AB  - BACKGROUND: Thiazolidine-2, 4-diones (TZDs) have become a pharmacologically
      important class of heterocyclic compounds since their introduction in the form of
      glitazones into the clinical use for the treatment of type 2 diabetes. TZDs lower
      the plasma glucose levels by acting as ligands for gamma peroxisome proliferators
      activated receptors. In addition, this class of heterocyclic compounds possesses
      various other biological activities such as antihyperglycemic, antimicrobial,
      anti-inflammatory, anticonvulsant, insecticidal, etc. TZDs are also known for
      lowering the blood pressure thereby reducing the chances of heart failure and
      micro-albuminuria in the patients with type 2 diabetes. RESULTS: We have
      described herein the synthesis of three series of compounds, namely, ethyl 2-((Z)
      5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3
      yl)acetates (4), methyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2,
      4-dioxothiazolidin-3-yl)acetates (5), and 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4
      yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetic acids (6). The compounds 4 and 5
      were synthesized by Knoevenagel condensation between 3-aryl-1-phenyl-1H-pyrazole
      4-carbaldehydes (1) and ethyl/methyl 2-(2, 4-dioxothiazolidin-3-yl)acetates (3,
      2) in alcohol using piperidine as a catalyst. The resultant compounds 4 and 5
      having ester functionality were subjected to acidic hydrolysis to obtain 6. All
      the new compounds were tested for their in vitro antibacterial and antifungal
      activity. CONCLUSIONS: Knoevenagel condensation approach has offered an easy
      access to new compounds 4-6. Antimicrobial evaluation of the compounds has shown
      that some of the compounds are associated with remarkable antifungal activity. In
      case of antibacterial activity, these were found to be effective against Gram
      positive bacteria. However, none of the compounds were found to be effective
      against Gram-negative bacteria.

PMID- 22373219
TI  - Influence of the nickel-titanium alloy components on biological functions.

PMID- 22373218
TI  - Monitoring physical and psychosocial symptom trajectories in ovarian cancer
      patients receiving chemotherapy.
AB  - BACKGROUND: Diagnosis and treatment of ovarian cancer (OC) entail severe symptom
      burden and a significant loss of quality of life (QOL). Somatic and psychological
      impairments may persist well beyond active therapy. Although essential for
      optimal symptom management as well as for the interpretation of treatment
      outcomes, knowledge on the course of QOL-related issues is scarce. This study
      aimed at assessing the course of depressive symptoms, anxiety, fatigue and QOL in
      patients with OC over the course of chemotherapy until early after-care. METHODS:
      23 patients were assessed longitudinally (eight time points) with regard to
      symptom burden (depression, anxiety, fatigue, and QOL) by means of patient
      reported outcome instruments (HADS, MFI-20, EORTC QLQ-C30/-OV28) and clinician
      ratings (HAMA/D) at each chemotherapy cycle and at the first two aftercare
      visits. RESULTS: Statistically significant decrease over time was found for
      depressive symptoms and anxiety as well as for all fatigue scales. With regard to
      QOL, results indicated significant increase for 11 of 15 QOL scales, best for
      Social (effect size = 1.95; p < 0.001), Emotional (e.s. = 1.62; p < 0.001) and
      Physical Functioning (e.s. = 1.47; p < 0.001). Abdominal Symptoms (e.s. = 1.01; p
      = 0.009) decreased, Attitudes towards Disease and Treatment (e.s. = 1.80; p <
      0.001) improved significantly over time. Analysis of Sexual Functioning was not
      possible due to a high percentage of missing responses (61.9%). CONCLUSIONS: The
      present study underlines the importance of longitudinal assessment of QOL in
      order to facilitate the identification of symptom burden in OC patients. We found
      that patients show high levels of fatigue, anxiety and depressive symptoms and
      severely impaired QOL post-surgery (i.e. at start of chemotherapy) but condition
      improves considerably throughout chemotherapy reaching nearly general population
      symptoms levels until aftercare.

PMID- 22373222
TI  - Complex medium supplements optimized for the reduction of animal-derived
      components in vaccine production media.

PMID- 22373223
TI  - Search for compound heterozygous effects in exome sequence of unrelated subjects.
AB  - To enable the assessment of compound heterozygosity, we propose a simple approach
      for incorporating genotype phase in a rare variant collapsing procedure for the
      analysis of DNA sequence data. When multiple variants are identified within a
      gene, knowing the phase of each variant may provide additional statistical power
      to detect associations with phenotypes that follow a recessive or additive
      inheritance pattern. We begin by phasing all marker data; then, we collapse
      nonsynonymous single-nucleotide polymorphisms within genes on each phased
      haplotype, resulting in a single diploid genotype for each gene, which represents
      whether one or both haplotypes carry a nonsynonymous variant allele. A recessive
      or additive association test can then be used to assess the relationship between
      the collapsed genotype and the phenotype of interest. We apply this approach to
      the unrelated individuals data from Genetic Analysis Workshop 17 and compare the
      results of the additive test with a dominant test in which phase is not
      informative. Analysis of the first phenotype replicate shows that the FLT1 gene
      is significantly associated with both Q1 and the binary affection status
      phenotype. This association was detected by both the additive and dominant tests,
      although the additive phase-informed test resulted in a smaller p-value. No false
      positive results were detected in the first phenotype replicate. Analysis of the
      average values of all phenotype replicates correctly identified five other genes
      important to the simulation, but with an increase in false-positive rates. The
      accuracy of our method is contingent on correct phase determination.

PMID- 22373224
TI  - Process development of ATROSAB, an anti TNFR1 Monoclonal Antibody: in three steps
      from research to GMP.

PMID- 22373228
TI  - Pathway analysis for family data using nested random-effects models.
AB  - Recently we proposed a novel two-step approach to test for pathway effects in
      disease progression. The goal of this approach is to study the joint effect of
      multiple single-nucleotide polymorphisms that belong to certain genes. By using
      random effects, our approach acknowledges the correlations within and between
      genes when testing for pathway effects. Gene-gene and gene-environment
      interactions can be included in the model. The method can be implemented with
      standard software, and the distribution of the test statistics under the null
      hypothesis can be approximated by using standard chi-square distributions. Hence
      no extensive permutations are needed for computations of the p-value. In this
      paper we adapt and apply the method to family data, and we study its performance
      for sequence data from Genetic Analysis Workshop 17. For the set of unrelated
      subjects, the performance of the new test was disappointing. We found a power of
      6% for the binary outcome and of 18% for the quantitative trait Q1. For family
      data the new approach appears to perform well, especially for the quantitative
      outcome. We found a power of 39% for the binary outcome and a power of 89% for
      the quantitative trait Q1.

PMID- 22373225
TI  - High-capacity assay to quantify the clonal heterogeneity in potency of
      mesenchymal stem cells.

PMID- 22373230
TI  - Improved power by collapsing rare and common variants based on a data-adaptive
      forward selection strategy.
AB  - Genome-wide association studies have been used successfully to detect
      associations between common genetic variants and complex diseases, but common
      single-nucleotide polymorphisms (SNPs) detected by these studies explain only 5
      10% of disease heritability. Alternatively, the common disease/rare variants
      hypothesis suggests that complex diseases are often caused by multiple rare
      variants with moderate to high effects. Under this hypothesis, the analysis of
      the cumulative effect of rare variants may thus help us discover the missing
      genetic variations. Collapsing all rare variants across a functional region is
      currently a popular method to find rare variants that may have a causal effect on
      certain diseases. However, the power of tests based on collapsing methods is
      often impaired by misclassification of functional variants. We develop a data
      adaptive forward selection procedure that selectively chooses only variants that
      improve the association signal between functional regions and the disease risk.
      We apply our strategy to the Genetic Analysis Workshop 17 unrelated individuals
      data with quantitative traits. The type I error rate and the power of different
      collapsing functions are evaluated. The substantially higher power of the
      proposed strategy was demonstrated. The new method provides a useful strategy for
      the association study of sequencing data by taking advantage of the selection of
      rare variants.

PMID- 22373231
TI  - Design and simulation of a controller system for metabolic shift regulation in
      mammalian cells.

PMID- 22373232
TI  - Strategies for selection of subjects for sequencing after detection of a linkage
      peak.
AB  - Linkage analysis has the potential to localize disease genes of interest, but the
      choice of which subjects to select for follow-up sequencing after identifying a
      linkage peak might influence the ability to find a disease gene. We compare nine
      different strategies for selection of subjects for follow-up sequencing using
      sequence data from the Genetic Analysis Workshop 17. We found that our more
      selective strategies, which included methods to identify case subjects more
      likely to be affected by genetic causes, out-performed sequencing all case and
      control subjects in linked pedigrees and required sequencing fewer individuals.
      We found that using genotype data from population control subjects had a higher
      benefit-cost ratio than sequencing control subjects selected as being the
      opposite extreme of the case subjects. We conclude that choosing case subjects
      for sequencing based on more selective strategies can be reliable and cost
      effective. 

PMID- 22373233
TI  - The Biodiversity Informatics Potential Index.
AB  - BACKGROUND: Biodiversity informatics is a relatively new discipline extending
      computer science in the context of biodiversity data, and its development to date
      has not been uniform throughout the world. Digitizing effort and capacity
      building are costly, and ways should be found to prioritize them rationally. The
      proposed 'Biodiversity Informatics Potential (BIP) Index' seeks to fulfill such a
      prioritization role. We propose that the potential for biodiversity informatics
      be assessed through three concepts: (a) the intrinsic biodiversity potential (the
      biological richness or ecological diversity) of a country; (b) the capacity of
      the country to generate biodiversity data records; and (c) the availability of
      technical infrastructure in a country for managing and publishing such records.
      METHODS: Broadly, the techniques used to construct the BIP Index were rank
      correlation, multiple regression analysis, principal components analysis and
      optimization by linear programming. We built the BIP Index by finding a
      parsimonious set of country-level human, economic and environmental variables
      that best predicted the availability of primary biodiversity data accessible
      through the Global Biodiversity Information Facility (GBIF) network, and
      constructing an optimized model with these variables. The model was then applied
      to all countries for which sufficient data existed, to obtain a score for each
      country. Countries were ranked according to that score. RESULTS: Many of the
      current GBIF participants ranked highly in the BIP Index, although some of them
      seemed not to have realized their biodiversity informatics potential. The BIP
      Index attributed low ranking to most nonparticipant countries; however, a few of
      them scored highly, suggesting that these would be high-return new participants
      if encouraged to contribute towards the GBIF mission of free and open access to
      biodiversity data. CONCLUSIONS: The BIP Index could potentially help in (a)
      identifying countries most likely to contribute to filling gaps in digitized
      biodiversity data; (b) assisting countries potentially in need (for example mega
      diverse) to mobilize resources and collect data that could be used in decision
      making; and (c) allowing identification of which biodiversity informatics
      resourced countries could afford to assist countries lacking in biodiversity
      informatics capacity, and which data-rich countries should benefit most from such
      help.

PMID- 22373235
TI  - Determination of intracellular antibody production, cell density, and viability
      of recombinant CHO-DG44 cells using the MACSQuant(r) Analyzer.

PMID- 22373237
TI  - Evaluation of three commercial kits for mycoplasma NAT assays: selection and
      quality improvement.

PMID- 22373236
TI  - Nbeta-methylation changes the recognition pattern of aza-beta3-amino acid
      containing peptidomimetic substrates by protein kinase A.
AB  - The protein kinase A (PKA)-catalyzed phosphorylation of peptide substrate RRASVA
      analogs, containing Nbeta-Me-aza-beta3-amino acid residues in all subsequent
      positions, was studied. This work follows along the lines of our previous
      research of the phosphorylation of aza-beta3-analogs of RRASVA (the shortest
      active substrate of PKA) and allows characterizing the influence of Nbeta
      methylation of aza-beta3-amino acid residues on substrate recognition by PKA on
      substrate binding and phosphorylation steps. It was found that the effect of
      Nbeta-methylation was dependent upon the position of the structure alteration.
      Moreover, the presence of a single Nbeta-methylation site in the substrate
      changed the recognition pattern of this series of peptidomimetics, strongly
      affecting the phosphorylation step. Structure modeling of aza-beta3- and Nbeta-Me
      aza-beta3-containing substrates revealed that Nbeta-methylation of aza-beta3
      moieties changed the peptide bond geometry from trans- to cis-configuration in 
      CO-NMe- fragments, with an exception for the N-terminally methylated Nbeta-Me-aza
      beta3-RRRASVA (with the N-terminal amino group not participating in the peptide
      bond) and RRAS-Nbeta-Me-aza-beta3-VA. As has been shown in literature, this
      conformational preference of the backbone has a significant influence on the
      flexibility of the peptide substrate chain. Following our results, this property
      seems to have significant influence on the recognition of the amino acid side
      groups by the enzyme binding site, and in the case of PKA this structural
      modification was decisive for the phosphate transfer step of the catalytic
      process.

PMID- 22373238
TI  - PTIGS-IdIt, a system for species identification by DNA sequences of the psbA-trnH
      intergenic spacer region.
AB  - BACKGROUND: DNA barcoding technology, which uses a short piece of DNA sequence to
      identify species, has wide ranges of applications. Until today, a universal DNA
      barcode marker for plants remains elusive. The rbcL and matK regions have been
      proposed as the "core barcode" for plants and the ITS2 and psbA-trnH intergenic
      spacer (PTIGS) regions were later added as supplemental barcodes. The use of
      PTIGS region as a supplemental barcode has been limited by the lack of
      computational tools that can handle significant insertions and deletions in the
      PTIGS sequences. Here, we compared the most commonly used alignment-based and
      alignment-free methods and developed a web server to allow the biologists to
      carry out PTIGS-based DNA barcoding analyses. RESULTS: First, we compared several
      alignment-based methods such as BLAST and those calculating P distance and Edit
      distance, alignment-free methods Di-Nucleotide Frequency Profile (DNFP) and their
      combinations. We found that the DNFP and Edit-distance methods increased the
      identification success rate to ~80%, 20% higher than the most commonly used BLAST
      method. Second, the combined methods showed overall better success rate and
      performance. Last, we have developed a web server that allows (1) retrieving
      various sub-regions and the consensus sequences of PTIGS, (2) annotating novel
      PTIGS sequences, (3) determining species identity by PTIGS sequences using eight
      methods, and (4) examining identification efficiency and performance of the eight
      methods for various taxonomy groups. CONCLUSIONS: The Edit distance and the DNFP
      methods have the highest discrimination powers. Hybrid methods can be used to
      achieve significant improvement in performance. These methods can be extended to
      applications using the core barcodes and the other supplemental DNA barcode ITS2.
      To our knowledge, the web server developed here is the only one that allows
      species determination based on PTIGS sequences. The web server can be accessed at
      http://psba-trnh-plantidit.dnsalias.org.

PMID- 22373239
TI  - In-situ cell density monitoring and apoptosis detection in adherent Vero cell
      bioreactor cultures.

PMID- 22373241
TI  - Cell line development using the SEFEX system.

PMID- 22373240
TI  - Isolation and genomic analysis of circulating tumor cells from castration
      resistant metastatic prostate cancer.
AB  - BACKGROUND: The number of circulating tumor cells (CTCs) in metastatic prostate
      cancer patients provides prognostic and predictive information. However, it is
      the molecular characterization of CTCs that offers insight into the biology of
      these tumor cells in the context of personalized treatment. METHODS: We developed
      a novel approach to isolate CTCs away from hematopoietic cells with high purity,
      enabling genomic analysis of these cells. The isolation protocol involves
      immunomagnetic enrichment followed by fluorescence activated cell sorting
      (IE/FACS). To evaluate the feasibility of isolation of CTCs by IE/FACS and
      downstream genomic profiling, we conducted a pilot study in patients with
      metastatic castration resistant prostate cancer (CRPC). Twenty (20) sequential
      CRPC patients were assayed using CellSearchTM. Twelve (12) patients positive for
      CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell
      sorting (IE/FACS) to isolate CTCs. Genomic DNA of CTCs was subjected to whole
      genome amplification (WGA) followed by gene copy number analysis via array
      comparative genomic hybridization (aCGH). RESULTS: CTCs from nine (9) patients
      successfully profiled were observed to have multiple copy number aberrations
      including those previously reported in primary prostate tumors such as gains in
      8q and losses in 8p. High-level copy number gains at the androgen receptor (AR)
      locus were observed in 7 (78%) cases. Comparison of genomic profiles between CTCs
      and archival primary tumors from the same patients revealed common lineage.
      However, high-level copy number gains in the AR locus were observed in CTCs, but
      not in the matched archival primary tumors. CONCLUSIONS: We developed a new
      approach to isolate prostate CTCs without significant leukocyte admixture, and to
      subject them to genome-wide copy number analysis. Our assay may be utilized to
      explore genomic events involved in cancer progression, e.g. development of
      castration resistance and to monitor therapeutic efficacy of targeted therapies
      in clinical trials in a relatively non-invasive manner.

PMID- 22373242
TI  - Comparison of SNP-based and gene-based association studies in detecting rare
      variants using unrelated individuals.
AB  - We compare the SNP-based and gene-based association studies using 697 unrelated
      individuals. The Benjamini-Hochberg procedure was applied to control the false
      discovery rate for all the multiple comparisons. We use a linear model for the
      single-nucleotide polymorphism (SNP) based association study. For the gene-based
      study, we consider three methods. The first one is based on a linear model, the
      second is similarity based, and the third is a new two-step procedure. The
      results of power using a subset of SNPs show that the SNP-based association test
      is more powerful than the gene-based ones. However, in some situations, a gene
      based study is able to detect the associated variants that were neglected in a
      SNP-based study. Finally, we apply these methods to a replicate of the
      quantitative trait Q1 and the binary trait D (D = 1, affected; D = 0, unaffected)
      for a genome-wide gene search.

PMID- 22373243
TI  - Influence of operating parameters of a settling-based perfusion process on
      expansion of VERO cells attached on microcarriers.

PMID- 22373246
TI  - An aggregating U-Test for a genetic association study of quantitative traits.
AB  - We propose a novel aggregating U-test for gene-based association analysis. The
      method considers both rare and common variants. It adaptively searches for
      potential disease-susceptibility rare variants and collapses them into a single
      "supervariant." A forward U-test is then used to assess the joint association of
      the supervariant and other common variants with quantitative traits. Using 200
      simulated replicates from the Genetic Analysis Workshop 17 mini-exome data, we
      compare the performance of the proposed method with that of a commonly used
      approach, QuTie. We find that our method has an equivalent or greater power than
      QuTie to detect nine genes that influence the quantitative trait Q1. This new
      approach provides a powerful tool for detecting both common and rare variants
      associated with quantitative traits.

PMID- 22373247
TI  - Resampling procedures to identify important SNPs using a consensus approach.
AB  - Our goal is to identify common single-nucleotide polymorphisms (SNPs) (minor
      allele frequency > 1%) that add predictive accuracy above that gained by
      knowledge of easily measured clinical variables. We take an algorithmic approach
      to predict each phenotypic variable using a combination of phenotypic and
      genotypic predictors. We perform our procedure on the first simulated replicate
      and then validate against the others. Our procedure performs well when predicting
      Q1 but is less successful for the other outcomes. We use resampling procedures
      where possible to guard against false positives and to improve generalizability.
      The approach is based on finding a consensus regarding important SNPs by applying
      random forests and the least absolute shrinkage and selection operator (LASSO) on
      multiple subsamples. Random forests are used first to discard unimportant
      predictors, narrowing our focus to roughly 100 important SNPs. A cross-validation
      LASSO is then used to further select variables. We combine these procedures to
      guarantee that cross-validation can be used to choose a shrinkage parameter for
      the LASSO. If the clinical variables were unavailable, this prefiltering step
      would be essential. We perform the SNP-based analyses simultaneously rather than
      one at a time to estimate SNP effects in the presence of other causal variants.
      We analyzed the first simulated replicate of Genetic Analysis Workshop 17 without
      knowledge of the true model. Post-conference knowledge of the simulation
      parameters allowed us to investigate the limitations of our approach. We found
      that many of the false positives we identified were substantially correlated with
      genuine causal SNPs.

PMID- 22373248
TI  - Application of complex and chemically-defined medium supplements toward cell line
      specific performance enhancement of biopharmaceutical production systems.

PMID- 22373249
TI  - Comparison of collapsing methods for the statistical analysis of rare variants.
AB  - Novel technologies allow sequencing of whole genomes and are considered as an
      emerging approach for the identification of rare disease-associated variants.
      Recent studies have shown that multiple rare variants can explain a particular
      proportion of the genetic basis for disease. Following this assumption, we
      compare five collapsing approaches to test for groupwise association with disease
      status, using simulated data provided by Genetic Analysis Workshop 17 (GAW17).
      Variants are collapsed in different scenarios per gene according to different
      minor allele frequency (MAF) thresholds and their functionality. For comparing
      the different approaches, we consider the family-wise error rate and the power.
      Most of the methods could maintain the nominal type I error levels well for small
      MAF thresholds, but the power was generally low. Although the methods considered
      in this report are common approaches for analyzing rare variants, they performed
      poorly with respect to the simulated disease phenotype in the GAW17 data set.

PMID- 22373254
TI  - Detecting disease rare alleles using single SNPs in families and haplotyping in
      unrelated subjects from the Genetic Analysis Workshop 17 data.
AB  - We present an evaluation of discovery power for two association tests that work
      well with common alleles but are applied to the Genetic Analysis Workshop 17
      simulations with rare causative single-nucleotide polymorphisms (SNPs) (minor
      allele frequency [MAF] < 1%). The methods used were genome-wide single-SNP
      association tests based on a linear mixed-effects model for discovery and applied
      to the familial sample and sliding windows haplotype association tests for
      replication, implemented within causative genes in the unrelated individuals
      sample. Both methods are evaluated with respect to the simulated trait Q2. The
      linear mixed-effects model and haplotype association tests failed to detect the
      rare alleles of the simulated associations. In contrast, the linear mixed-effects
      model and haplotype association tests detected effects for the most important
      simulated SNPs with MAF > 1%. We conclude that these findings reflect inadequate
      statistical power (the result of small simulated samples) for the complex genetic
      model that underlies these data.

PMID- 22373255
TI  - Disulphide bond reduction of a therapeutic monoclonal antibody during cell
      culture manufacturing operations.

PMID- 22373256
TI  - Large pilot scale cultivation process study of adherent MDBK cells for porcine
      Influenza A virus propagation using a novel disposable stirred-tank bioreactor.

PMID- 22373257
TI  - Data hosting infrastructure for primary biodiversity data.
AB  - BACKGROUND: Today, an unprecedented volume of primary biodiversity data are being
      generated worldwide, yet significant amounts of these data have been and will
      continue to be lost after the conclusion of the projects tasked with collecting
      them. To get the most value out of these data it is imperative to seek a solution
      whereby these data are rescued, archived and made available to the biodiversity
      community. To this end, the biodiversity informatics community requires
      investment in processes and infrastructure to mitigate data loss and provide
      solutions for long-term hosting and sharing of biodiversity data. DISCUSSION: We
      review the current state of biodiversity data hosting and investigate the
      technological and sociological barriers to proper data management. We further
      explore the rescuing and re-hosting of legacy data, the state of existing
      toolsets and propose a future direction for the development of new discovery
      tools. We also explore the role of data standards and licensing in the context of
      data hosting and preservation. We provide five recommendations for the
      biodiversity community that will foster better data preservation and access: (1)
      encourage the community's use of data standards, (2) promote the public domain
      licensing of data, (3) establish a community of those involved in data hosting
      and archival, (4) establish hosting centers for biodiversity data, and (5)
      develop tools for data discovery. CONCLUSION: The community's adoption of
      standards and development of tools to enable data discovery is essential to
      sustainable data preservation. Furthermore, the increased adoption of open
      content licensing, the establishment of data hosting infrastructure and the
      creation of a data hosting and archiving community are all necessary steps
      towards the community ensuring that data archival policies become standardized.

PMID- 22373259
TI  - Recombinant antibody mixtures; optimization of cell line generation and single
      batch manufacturing processes.

PMID- 22373260
TI  - Prediction of dinucleotide-specific RNA-binding sites in proteins.
AB  - BACKGROUND: Regulation of gene expression, protein synthesis, replication and
      assembly of many viruses involve RNA-protein interactions. Although some
      successful computational tools have been reported to recognize RNA binding sites
      in proteins, the problem of specificity remains poorly investigated. After the
      nucleotide base composition, the dinucleotide is the smallest unit of RNA
      sequence information and many RNA-binding proteins simply bind to regions
      enriched in one dinucleotide. Interaction preferences of protein subsequences and
      dinucleotides can be inferred from protein-RNA complex structures, enabling a
      training-based prediction approach. RESULTS: We analyzed basic statistics of
      amino acid-dinucleotide contacts in protein-RNA complexes and found their pairing
      preferences could be identified. Using a standard approach to represent protein
      subsequences by their evolutionary profile, we trained neural networks to predict
      multiclass target vectors corresponding to 16 possible contacting dinucleotide
      subsequences. In the cross-validation experiments, the accuracies of the optimum
      network, measured as areas under the curve (AUC) of the receiver operating
      characteristic (ROC) graphs, were in the range of 65-80%. CONCLUSIONS:
      Dinucleotide-specific contact predictions have also been extended to the
      prediction of interacting protein and RNA fragment pairs, which shows the
      applicability of this method to predict targets of RNA-binding proteins. A web
      server predicting the 16-dimensional contact probability matrix directly from a
      user-defined protein sequence was implemented and made available at:
      http://tardis.nibio.go.jp/netasa/srcpred.

PMID- 22373261
TI  - Different approaches for dealing with rare variants in family-based genetic
      studies: application of a Genetic Analysis Workshop 17 problem.
AB  - Rare variants are becoming the new candidates in the search for genetic variants
      that predispose individuals to a phenotype of interest. Their low prevalence in a
      population requires the development of dedicated detection and analytical
      methods. A family-based approach could greatly enhance their detection and
      interpretation because rare variants are nearly family specific. In this report,
      we test several distinct approaches for analyzing the information provided by
      rare and common variants and how they can be effectively used to pinpoint
      putative candidate genes for follow-up studies. The analyses were performed on
      the mini-exome data set provided by Genetic Analysis Workshop 17. Eight
      approaches were tested, four using the trait's heritability estimates and four
      using QTDT models. These methods had their sensitivity, specificity, and positive
      and negative predictive values compared in light of the simulation parameters.
      Our results highlight important limitations of current methods to deal with rare
      and common variants, all methods presented a reduced specificity and,
      consequently, prone to false positive associations. Methods analyzing common
      variants information showed an enhanced sensibility when compared to rare
      variants methods. Furthermore, our limited knowledge of the use of biological
      databases for gene annotations, possibly for use as covariates in regression
      models, imposes a barrier to further research.

PMID- 22373262
TI  - Use of health services by remote dwelling Aboriginal infants in tropical northern
      Australia: a retrospective cohort study.
AB  - BACKGROUND: Australia is a wealthy developed country. However, there are
      significant disparities in health outcomes for Aboriginal infants compared with
      other Australian infants. Health outcomes tend to be worse for those living in
      remote areas. Little is known about the health service utilisation patterns of
      remote dwelling Aboriginal infants. This study describes health service
      utilisation patterns at the primary and referral level by remote dwelling
      Aboriginal infants from northern Australia. RESULTS: Data on 413 infants were
      analysed. Following birth, one third of infants were admitted to the regional
      hospital neonatal nursery, primarily for preterm birth. Once home, most (98%)
      health service utilisation occurred at the remote primary health centre, infants
      presented to the centre about once a fortnight (mean 28 presentations per year,
      95%CI 26.4-30.0). Half of the presentations were for new problems, most commonly
      for respiratory, skin and gastrointestinal symptoms. Remaining presentations were
      for reviews or routine health service provision. By one year of age 59% of
      infants were admitted to hospital at least once, the rate of hospitalisation per
      infant year was 1.1 (95%CI 0.9-1.2). CONCLUSIONS: The hospitalisation rate is
      high and admissions commence early in life, visits to the remote primary health
      centre are frequent. Half of all presentations are for new problems. These
      findings have important implications for health service planning and delivery to
      remote dwelling Aboriginal families.

PMID- 22373263
TI  - Metabolomics - a useful tool for prediction of protein production and processing?

PMID- 22373264
TI  - Platform process for production of monoclonal antibodies for research purposes -
      improvement option.

PMID- 22373266
TI  - LASSO model selection with post-processing for a genome-wide association study
      data set.
AB  - Model selection procedures for simultaneous analysis of all single-nucleotide
      polymorphisms in genome-wide association studies are most suitable for making
      full use of the data for a complex disease study. In this paper we consider a
      penalized regression using the LASSO procedure and show that post-processing of
      the penalized-regression results with subsequent stepwise selection may lead to
      improved identification of causal single-nucleotide polymorphisms.

PMID- 22373267
TI  - Collapsing ROC approach for risk prediction research on both common and rare
      variants.
AB  - Risk prediction that capitalizes on emerging genetic findings holds great promise
      for improving public health and clinical care. However, recent risk prediction
      research has shown that predictive tests formed on existing common genetic loci,
      including those from genome-wide association studies, have lacked sufficient
      accuracy for clinical use. Because most rare variants on the genome have not yet
      been studied for their role in risk prediction, future disease prediction
      discoveries should shift toward a more comprehensive risk prediction strategy
      that takes into account both common and rare variants. We are proposing a
      collapsing receiver operating characteristic (CROC) approach for risk prediction
      research on both common and rare variants. The new approach is an extension of a
      previously developed forward ROC (FROC) approach, with additional procedures for
      handling rare variants. The approach was evaluated through the use of 533 single
      nucleotide polymorphisms (SNPs) in 37 candidate genes from the Genetic Analysis
      Workshop 17 mini-exome data set. We found that a prediction model built on all
      SNPs gained more accuracy (AUC = 0.605) than one built on common variants alone
      (AUC = 0.585). We further evaluated the performance of two approaches by
      gradually reducing the number of common variants in the analysis. We found that
      the CROC method attained more accuracy than the FROC method when the number of
      common variants in the data decreased. In an extreme scenario, when there are
      only rare variants in the data, the CROC reached an AUC value of 0.603, whereas
      the FROC had an AUC value of 0.524.

PMID- 22373268
TI  - 3D-Bioreactor culture of human hepatoma cell line HepG2 as a promising tool for
      in vitro substance testing.

PMID- 22373269
TI  - Bioreactor cultivation of CHO DP-12 cells under sodium butyrate treatment -
      comparative transcriptome analysis with CHO cDNA microarrays.

PMID- 22373271
TI  - A weighted accumulation test for associating rare genetic variation with
      quantitative phenotypes.
AB  - Currently there is a great deal of interest in developing methods for testing the
      role that rare variation plays in disease development. Here we propose a weighted
      association test that accumulates genetic variation across a signaling pathway.
      We evaluate our approach by analyzing simulated phenotype data from an exome
      sequencing study of 697 unrelated individuals from the Genetic Analysis Workshop
      17 (GAW17) data set. Although our weighted approach identifies several
      interesting pathways associated with phenotype Q1, so does an alternative
      unweighted accumulation approach. Such a result is not unexpected because there
      is no systematic relationship between the allele frequency of a variant and its
      effect on phenotype in the GAW17 simulation model.

PMID- 22373273
TI  - A comparison of performance enhancing synergy among ultrafiltered yeast extracts
      and recombinant human serum albumin in CHO-K1 cells.

PMID- 22373274
TI  - Semantic Web applications and tools for the life sciences: SWAT4LS 2010.
AB  - As Semantic Web technologies mature and new releases of key elements, such as
      SPARQL 1.1 and OWL 2.0, become available, the Life Sciences continue to push the
      boundaries of these technologies with ever more sophisticated tools and
      applications. Unsurprisingly, therefore, interest in the SWAT4LS (Semantic Web
      Applications and Tools for the Life Sciences) activities have remained high, as
      was evident during the third international SWAT4LS workshop held in Berlin in
      December 2010. Contributors to this workshop were invited to submit extended
      versions of their papers, the best of which are now made available in the special
      supplement of BMC Bioinformatics. The papers reflect the wide range of work in
      this area, covering the storage and querying of Life Sciences data in RDF triple
      stores, tools for the development of biomedical ontologies and the semantics
      based integration of Life Sciences as well as clinicial data. 

PMID- 22373278
TI  - Accelerating process development through analysis of cell metabolism.

PMID- 22373280
TI  - Preliminary evaluation of microcarrier culture for growth and monoclonal antibody
      production of CHO-K1 cells.

PMID- 22373282
TI  - Effect of population stratification analysis on false-positive rates for common
      and rare variants.
AB  - Principal components analysis (PCA) has been successfully used to correct for
      population stratification in genome-wide association studies of common variants.
      However, rare variants also have a role in common disease etiology. Whether PCA
      successfully controls population stratification for rare variants has not been
      addressed. Thus we evaluate the effect of population stratification analysis on
      false-positive rates for common and rare variants at the single-nucleotide
      polymorphism (SNP) and gene level. We use the simulation data from Genetic
      Analysis Workshop 17 and compare false-positive rates with and without PCA at the
      SNP and gene level. We found that SNPs' minor allele frequency (MAF) influenced
      the ability of PCA to effectively control false discovery. Specifically, PCA
      reduced false-positive rates more effectively in common SNPs (MAF > 0.05) than in
      rare SNPs (MAF < 0.01). Furthermore, at the gene level, although false-positive
      rates were reduced, power to detect true associations was also reduced using PCA.
      Taken together, these results suggest that sequence-level data should be
      interpreted with caution, because extremely rare SNPs may exhibit sporadic
      association that is not controlled using PCA.

PMID- 22373285
TI  - Cell-based medicinal products and the development of GMP-compliant processes and
      manufacturing.

PMID- 22373286
TI  - Effect of influenza virus infection on key metabolic enzyme activities in MDCK
      cells.

PMID- 22373281
TI  - A 'snip' in time: what is the best age to circumcise?
AB  - BACKGROUND: Circumcision is a common procedure, but regional and societal
      attitudes differ on whether there is a need for a male to be circumcised and, if
      so, at what age. This is an important issue for many parents, but also
      pediatricians, other doctors, policy makers, public health authorities, medical
      bodies, and males themselves. DISCUSSION: We show here that infancy is an optimal
      time for clinical circumcision because an infant's low mobility facilitates the
      use of local anesthesia, sutures are not required, healing is quick, cosmetic
      outcome is usually excellent, costs are minimal, and complications are uncommon.
      The benefits of infant circumcision include prevention of urinary tract
      infections (a cause of renal scarring), reduction in risk of inflammatory
      foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and
      paraphimosis. When the boy later becomes sexually active he has substantial
      protection against risk of HIV and other viral sexually transmitted infections
      such as genital herpes and oncogenic human papillomavirus, as well as penile
      cancer. The risk of cervical cancer in his female partner(s) is also reduced.
      Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage
      or reduced sexual pleasure, even though unfounded. Time off work or school will
      be needed, cost is much greater, as are risks of complications, healing is
      slower, and stitches or tissue glue must be used. SUMMARY: Infant circumcision is
      safe, simple, convenient and cost-effective. The available evidence strongly
      supports infancy as the optimal time for circumcision.

PMID- 22373287
TI  - Using linkage analysis of large pedigrees to guide association analyses.
AB  - To date, genome-wide association studies have yielded discoveries of common
      variants that partly explain familial aggregation of diseases and traits.
      Researchers are now turning their attention to less common variants because the
      price of sequencing has dropped drastically. However, because sequencing of the
      whole genome in large samples is costly, great care must be taken to prioritize
      which samples and which genomic regions are selected for sequencing. We are
      interested in identifying genomic regions for deep sequencing using large
      multiplex families collected as part of earlier linkage studies. We incorporate
      linkage analysis into our search for Q1-associated alleles. Overall, we found
      that power was low for both whole-exome and linkage-guided sequencing analysis.
      By restricting sequencing to regions with high LOD peaks, we found fewer
      associated single-nucleotide polymorphisms than by using whole-exome sequencing.
      However, incorporating linkage analysis enabled us to detect more than half of
      the associated susceptibility loci (52%) that would have been identified by whole
      exome sequencing while examining only 2.5% of the exome. This result suggests
      that incorporating linkage results from large multiplex families might greatly
      increase the efficiency of sequencing to detect trait-associated alleles in
      complex disease.

PMID- 22373288
TI  - PB1-F2 Finder: scanning influenza sequences for PB1-F2 encoding RNA segments.
AB  - BACKGROUND: PB1-F2 is a major virulence factor of influenza A. This protein is a
      product of an alternative reading frame in the PB1-encoding RNA segment 2. Its
      presence of is dictated by the presence or absence of premature stop codons. This
      virulence factor is present in every influenza pandemic and major epidemic of the
      20th century. Absence of PB1-F2 is associated with mild disease, such as the 2009
      H1N1 ("swine flu"). RESULTS: The analysis of 8608 segment 2 sequences showed that
      only 8.5% have been annotated for the presence of PB1-F2. Our analysis indicates
      that 75% of segment 2 sequences are likely to encode PB1-F2. Two major
      populations of PB1-F2 are of lengths 90 and 57 while minor populations include
      lengths 52, 63, 79, 81, 87, and 101. Additional possible populations include the
      lengths of 59, 69, 81, 95, and 106. Previously described sequences include only
      lengths 57, 87, and 90. We observed substantial variation in PB1-F2 sequences
      where certain variants show up to 35% difference to well-defined reference
      sequences. Therefore this dataset indicates that there are many more variants
      that need to be functionally characterized. CONCLUSIONS: Our web-accessible tool
      PB1-F2 Finder enables scanning of influenza sequences for potential PB1-F2
      protein products. It provides an initial screen and annotation of PB1-F2
      products. It is accessible at http://cvc.dfci.harvard.edu/pb1-f2.

PMID- 22373289
TI  - Biosynthetic pathway deflection - a new cell line engineering approach.

PMID- 22373290
TI  - Interrogating population structure and its impact on association tests.
AB  - We found from our analysis of the Genetic Analysis Workshop 17 data that the
      population structure of the 697 unrelated individuals was an important
      confounding factor for association studies, even if it was not explicitly
      considered when simulating the phenotypes. We uncovered structures beyond the
      reported ethnicities and found ample evidence of phenotype-population structure
      associations. The first 10 principal components of the genotype data of the 697
      individuals demonstrated much stronger associations with Q1, Q2, and the disease
      than did the individuals' ethnicities. In addition, we observed that population
      structure was a confounding factor for the Q1-gene association when identifying
      the significant genes both with and without adjusting for the causal single
      nucleotide polymorphisms, the ethnicities, and the principal components. Many
      false discoveries remained after adjusting for the causal single-nucleotide
      polymorphisms. Adjusting for the principal components appeared more effective
      than did adjusting for ethnicity in terms of preventing false discoveries. This
      analysis was performed with knowledge of the causal loci.

PMID- 22373295
TI  - Strategies for adaptation of mAb-producing CHO cells to serum-free medium.

PMID- 22373294
TI  - Analogue-based approaches in anti-cancer compound modelling: the relevance of
      QSAR models.
AB  - BACKGROUND: QSAR is among the most extensively used computational methodology for
      analogue-based design. The application of various descriptor classes like quantum
      chemical, molecular mechanics, conceptual density functional theory (DFT)- and
      docking-based descriptors for predicting anti-cancer activity is well known.
      Although in vitro assay for anti-cancer activity is available against many
      different cell lines, most of the computational studies are carried out targeting
      insufficient number of cell lines. Hence, statistically robust and extensive QSAR
      studies against 29 different cancer cell lines and its comparative account, has
      been carried out. RESULTS: The predictive models were built for 266 compounds
      with experimental data against 29 different cancer cell lines, employing
      independent and least number of descriptors. Robust statistical analysis shows a
      high correlation, cross-validation coefficient values, and provides a range of
      QSAR equations. Comparative performance of each class of descriptors was carried
      out and the effect of number of descriptors (1-10) on statistical parameters was
      tested. Charge-based descriptors were found in 20 out of 39 models (approx. 50%),
      valency-based descriptor in 14 (approx. 36%) and bond order-based descriptor in
      11 (approx. 28%) in comparison to other descriptors. The use of conceptual DFT
      descriptors does not improve the statistical quality of the models in most cases.
      CONCLUSION: Analysis is done with various models where the number of descriptors
      is increased from 1 to 10; it is interesting to note that in most cases 3
      descriptor-based models are adequate. The study reveals that quantum chemical
      descriptors are the most important class of descriptors in modelling these series
      of compounds followed by electrostatic, constitutional, geometrical, topological
      and conceptual DFT descriptors. Cell lines in nasopharyngeal (2) cancer average
      R2 = 0.90 followed by cell lines in melanoma cancer (4) with average R2 = 0.81
      gave the best statistical values.

PMID- 22373298
TI  - Targeted metabolomics for bioprocessing.

PMID- 22373296
TI  - Classification of bipolar disorder in psychiatric hospital. A prospective cohort
      study.
AB  - BACKGROUND: This study has explored the classification of bipolar disorder in
      psychiatric hospital. A review of the literature reveals that there is a need for
      studies using stringent methodological approaches. METHODS: 480 first-time
      admitted patients to psychiatric hospital were found eligible and 271 of these
      gave written informed consent. The study sample was comprised of 250 patients
      (52%) with hospital diagnoses. For the study, expert diagnoses were given on the
      basis of a structured diagnostic interview (M.I.N.I.PLUS) and retrospective
      review of patient records. RESULTS: Agreement between the expert's and the
      clinicians' diagnoses was estimated using Cohen's kappa statistics. 76% of the
      primary diagnoses given by the expert were in the affective spectrum. Agreement
      concerning these disorders was moderate (kappa ranging from 0.41 to 0.47). Of 58
      patients with bipolar disorder, only 17 received this diagnosis in the clinic.
      Almost all patients with a current manic episode were classified as currently
      manic by the clinicians. Forty percent diagnosed as bipolar by the expert,
      received a diagnosis of unipolar depression by the clinician. Fifteen patients
      (26%) were not given a diagnosis of affective disorder at all. CONCLUSIONS: Our
      results indicate a considerable misclassification of bipolar disorder in
      psychiatric hospital, mainly in patients currently depressed. The importance of
      correctly diagnosing bipolar disorder should be emphasized both for clinical,
      administrative and research purposes. The findings questions the validity of
      psychiatric case registers. There are potential benefits in structuring the
      diagnostic process better in the clinic.

PMID- 22373299
TI  - Characterization of chromatographic yeast extract fractions promoting CHO cell
      growth.

PMID- 22373300
TI  - Population structure analysis using rare and common functional variants.
AB  - Next-generation sequencing technologies now make it possible to genotype and
      measure hundreds of thousands of rare genetic variations in individuals across
      the genome. Characterization of high-density genetic variation facilitates
      control of population genetic structure on a finer scale before large-scale
      genotyping in disease genetics studies. Population structure is a well-known,
      prevalent, and important factor in common variant genetic studies, but its
      relevance in rare variants is unclear. We perform an extensive population
      structure analysis using common and rare functional variants from the Genetic
      Analysis Workshop 17 mini-exome sequence. The analysis based on common functional
      variants required 388 principal components to account for 90% of the variation in
      population structure. However, an analysis based on rare variants required 532
      significant principal components to account for similar levels of variation.
      Using rare variants, we detected fine-scale substructure beyond the population
      structure identified using common functional variants. Our results show that the
      level of population structure embedded in rare variant data is different from the
      level embedded in common variant data and that correcting for population
      structure is only as good as the level one wishes to correct.

PMID- 22373301
TI  - Addition of multiple rare SNPs to known common variants improves the association
      between disease and gene in the Genetic Analysis Workshop 17 data.
AB  - The upcoming release of new whole-genome genotyping technologies will shed new
      light on whether there is an associative effect of previously immeasurable rare
      variants on incidence of disease. For Genetic Analysis Workshop 17, our team
      focused on a statistical method to detect associations between gene-based
      multiple rare variants and disease status. We added a combination of rare SNPs to
      a common variant shown to have an influence on disease status. This method
      provides us with an enhanced ability to detect the effect of these rare variants,
      which, modeled alone, would normally be undetectable. Adjusting for significant
      clinical parameters, several genes were found to have multiple rare variants that
      were significantly associated with disease outcome.

PMID- 22373302
TI  - Region-based and pathway-based QTL mapping using a p-value combination method.
AB  - Quantitative trait locus (QTL) mapping using deep DNA sequencing data is a
      challenging task. In this study we performed region-based and pathway-based QTL
      mappings using a p-value combination method to analyze the simulated quantitative
      traits Q1 and Q4 and the exome sequencing data. The aims were to evaluate the
      performance of the QTL mapping approaches that were used and to suggest plausible
      strategies for QTL mapping of DNA sequencing data. We conducted single-locus QTL
      mappings using a linear regression model with adjustments for age and smoking
      status, and we also conducted region-based and pathway-based QTL mappings using a
      truncated product method for combining p-values from the single-locus QTL
      mapping. To account for the features of rare variants and common single
      nucleotide polymorphisms (SNPs), we considered independently rare-variant-only,
      common-SNP-only, and combined analyses. An analysis of 200 simulated replications
      showed that the three region-based methods reasonably controlled type I error,
      whereas the combined analysis yielded the greatest statistical power. Rare
      variant-only, common-SNP-only, and combined analyses were also applied to pathway
      based QTL mappings. We found that pathway-based QTL mappings had a power of
      approximately 100% when the significance of the vascular endothelial growth
      factor pathway was evaluated, but type I errors were slightly inflated. Our
      approach complements single-locus QTL mapping. An integrated approach using
      single-locus, combined region-based, and combined pathway-based analyses should
      yield promising results for QTL mapping of DNA sequencing data.

PMID- 22373306
TI  - Improvement of stem cell performance by supplementation with metabolic enhancers.

PMID- 22373303
TI  - A semantic web framework to integrate cancer omics data with biological
      knowledge.
AB  - BACKGROUND: The RDF triple provides a simple linguistic means of describing
      limitless types of information. Triples can be flexibly combined into a unified
      data source we call a semantic model. Semantic models open new possibilities for
      the integration of variegated biological data. We use Semantic Web technology to
      explicate high throughput clinical data in the context of fundamental biological
      knowledge. We have extended Corvus, a data warehouse which provides a uniform
      interface to various forms of Omics data, by providing a SPARQL endpoint. With
      the querying and reasoning tools made possible by the Semantic Web, we were able
      to explore quantitative semantic models retrieved from Corvus in the light of
      systematic biological knowledge. RESULTS: For this paper, we merged semantic
      models containing genomic, transcriptomic and epigenomic data from melanoma
      samples with two semantic models of functional data - one containing Gene
      Ontology (GO) data, the other, regulatory networks constructed from transcription
      factor binding information. These two semantic models were created in an ad hoc
      manner but support a common interface for integration with the quantitative
      semantic models. Such combined semantic models allow us to pose significant
      translational medicine questions. Here, we study the interplay between a cell's
      molecular state and its response to anti-cancer therapy by exploring the
      resistance of cancer cells to Decitabine, a demethylating agent. CONCLUSIONS: We
      were able to generate a testable hypothesis to explain how Decitabine fights
      cancer - namely, that it targets apoptosis-related gene promoters predominantly
      in Decitabine-sensitive cell lines, thus conveying its cytotoxic effect by
      activating the apoptosis pathway. Our research provides a framework whereby
      similar hypotheses can be developed easily.

PMID- 22373307
TI  - "BioProzessTrainer" as training tool for design of experiments.

PMID- 22373309
TI  - Collapsing-based and kernel-based single-gene analyses applied to Genetic
      Analysis Workshop 17 mini-exome data.
AB  - Recently there has been great interest in identifying rare variants associated
      with common diseases. We apply several collapsing-based and kernel-based single
      gene association tests to Genetic Analysis Workshop 17 (GAW17) rare variant
      association data with unrelated individuals without knowledge of the simulation
      model. We also implement modified versions of these methods using additional
      information, such as minor allele frequency (MAF) and functional annotation. For
      each of four given traits provided in GAW17, we use the Bayesian mixed-effects
      model to estimate the phenotypic variance explained by the given environmental
      and genotypic data and to infer an individual-specific genetic effect to use
      directly in single-gene association tests. After obtaining information on the
      GAW17 simulation model, we compare the performance of all methods and examine the
      top genes identified by those methods. We find that collapsing-based methods with
      weights based on MAFs are sensitive to the "lower MAF, larger effect size"
      assumption, whereas kernel-based methods are more robust when this assumption is
      violated. In addition, many false-positive genes identified by multiple methods
      often contain variants with exactly the same genotype distribution as the causal
      variants used in the simulation model. When the sample size is much smaller than
      the number of rare variants, it is more likely that causal and noncausal variants
      will share the same or similar genotype distribution. This likely contributes to
      the low power and large number of false-positive results of all methods in
      detecting causal variants associated with disease in the GAW17 data set. 

PMID- 22373310
TI  - Evaluation of sampling and quenching procedures for the analysis of intracellular
      metabolites in CHO suspension cells.

PMID- 22373311
TI  - Development and validation of a protocol for cell line identification by MALDI
      TOF MS.

PMID- 22373312
TI  - Treating phenotype as given: a simple resampling method for genome-wide
      association studies.
AB  - Significance of genetic association to a marker has been traditionally evaluated
      through statistics that are standardized such that their null distributions
      conform to some known ones. Distributional assumptions are often required in this
      standardization procedure. Based on the observation that the phenotype remains
      the same regardless of the marker being investigated, we propose a simple
      statistic that does not need such standardization. We propose a resampling
      procedure to assess this statistic's genome-wide significance. This method has
      been applied to replicate 2 of the Genetic Analysis Workshop 17 simulated data on
      unrelated individuals in an attempt to map phenotype Q2. However, none of the
      selected SNPs are in genes that are disease-causing. This may be due to the weak
      effect that each genetic factor has on Q2.

PMID- 22373313
TI  - Prediction of RNA-binding amino acids from protein and RNA sequences.
AB  - BACKGROUND: Many learning approaches to predicting RNA-binding residues in a
      protein sequence construct a non-redundant training dataset based on the sequence
      similarity. The sequence similarity-based method either takes a whole sequence or
      discards it for a training dataset. However, similar sequences or even identical
      sequences can have different interaction sites depending on their interaction
      partners, and this information is lost when the sequences are removed.
      Furthermore, a training dataset constructed by the sequence similarity-based
      method may contain redundant data when the remaining sequence contains similar
      subsequences within the sequence. In addition to the problem with the training
      dataset, most approaches do not consider the interacting partner (i.e., RNA) of a
      protein when they predict RNA-binding amino acids. Thus, they always predict the
      same RNA-binding sites for a given protein sequence even if the protein binds to
      different RNA molecules. RESULTS: We developed a feature vector-based method that
      removes data redundancy for a non-redundant training dataset. The feature vector
      based method constructed a larger training dataset than the standard sequence
      similarity-based method, yet the dataset contained no redundant data. We
      identified effective features of protein and RNA (the interaction propensity of
      amino acid triplets, global features of the protein sequence, and RNA feature)
      for predicting RNA-binding residues. Using the method and features, we built a
      support vector machine (SVM) model that predicted RNA-binding residues in a
      protein sequence. Our SVM model showed an accuracy of 84.2%, an F-measure of
      76.1%, and a correlation coefficient of 0.41 with 5-fold cross validation on a
      non-redundant dataset from 3,149 protein-RNA interacting pairs. In an independent
      test dataset that does not include the 3,149 pairs and were not used in training
      the SVM model, it achieved an accuracy of 90.3%, an F-measure of 72.8%, and a
      correlation coefficient of 0.24. Comparison with other methods on the same
      datasets demonstrated that our model was better than the others. CONCLUSIONS: The
      feature vector-based redundancy reduction method is powerful for constructing a
      non-redundant training dataset for a learning model since it generates a larger
      dataset with non-redundant data than the standard sequence similarity-based
      method. Including the features of both RNA and protein sequences in a feature
      vector results in better performance than using the protein features only when
      predicting the RNA-binding residues in a protein sequence.

PMID- 22373314
TI  - Fluorescence-based tools to improve biopharmaceutical process development.

PMID- 22373316
TI  - Testing gene-environment interactions in gene-based association studies.
AB  - Gene-based and single-nucleotide polymorphism (SNP) set association studies
      provide an important complement to SNP analysis. Kernel-based nonparametric
      regression has recently emerged as a powerful and flexible tool for this purpose.
      Our goal is to explore whether this approach can be extended to incorporate and
      test for interaction effects, especially for genes containing rare variant SNPs.
      Here, we construct nonparametric regression models that can be used to include a
      gene-environment interaction effect under the framework of the least-squares
      kernel machine and examine the performance of the proposed method on the Genetic
      Analysis Workshop 17 unrelated individuals data set. Two hundred simulated
      replicates were used to explore the power for detecting interaction. We
      demonstrate through a genome scan of the quantitative phenotype Q1 that the
      simulated gene-environment interaction effect in the data can be detected with
      reasonable power by using the least-squares kernel machine method.

PMID- 22373319
TI  - A novel method to detect rare variants using both family and unrelated case
      control data.
AB  - To detect rare variants associated with a phenotype, we develop a novel
      statistical method that can use both family and unrelated case-control data.
      Unlike the currently existing methods, we first use family data to calculate
      weights to be given to rare variants, differentiating between concordantly
      affected and discordant sib pairs. These weights are then used in an association
      test applied to the unrelated case-control data. We applied the proposed method
      to the simulated sequencing data in Genetic Analysis Workshop 17 and identified
      two genes associated with the disease.

PMID- 22373320
TI  - Impact of different influenza cultivation conditions on HA N-Glycosylation.

PMID- 22373322
TI  - Toolbox approach for fast generation of stable CHO production cell lines from
      different hosts.

PMID- 22373323
TI  - Design, synthesis and antimicrobial evaluation of novel 2-aryl-thiazolidin-4-one
      derivatives.
AB  - Novel 2-arylthiazolidin-4-one derivatives (8a-q and 11) have been synthesized in
      good-to-excellent yields (70-96%) by one-pot three-component condensation
      cyclization reaction of aromatic or aliphatic primary amines, aromatic aldehydes,
      and thioglycolic acid in polypropylene glycol at 110 degrees C temperature. The
      in vitro antimicrobial activity of the synthesized 2-arylthiazolidin-4-ones was
      investigated against a panel of six pathogenic fungal strains, a Gram-positive
      and three Gram-negative bacteria. Results revealed that the compounds (8a-d)
      bearing 3-(4-(1H-imidazolylmethyl)phenyl)-substituent displayed significant
      antibacterial efficacy specifically against Klebsiella pneumoniae (minimum
      inhibitory concentration 12.5 MUg/mL). In addition, some of the synthesized
      compounds have also shown antimicotic activity against Sporothrix schenckii,
      Trichophyton mentagrophytes, and Aspergillus fumigatus at the concentration of 50
      MUg/mL.

PMID- 22373324
TI  - Detecting functional rare variants by collapsing and incorporating functional
      annotation in Genetic Analysis Workshop 17 mini-exome data.
AB  - Association studies using tag SNPs have been successful in detecting disease
      associated common variants. However, common variants, with rare exceptions,
      explain only at most 5-10% of the heritability resulting from genetic factors,
      which leads to the common disease/rare variants assumption. Indeed, recent
      studies using sequencing technologies have demonstrated that common diseases can
      be due to rare variants that could not be systematically studied earlier.
      Unfortunately, methods for common variants are not optimal if applied to rare
      variants. To identify rare variants that affect disease risk, several
      investigators have designed new approaches based on the idea of collapsing
      different rare variants inside the same genomic block (e.g., the same gene or
      pathway) to enrich the signal. Here, we consider three different collapsing
      methods in the multimarker regression model and compared their performance on the
      Genetic Analysis Workshop 17 data using the consistency of results across
      different simulations and the cross-validation prediction error rate. The
      comparison shows that the proportion collapsing method seems to outperform the
      other two methods and can find both truly associated rare and common variants.
      Moreover, we explore one way of incorporating the functional annotations for the
      variants in the data that collapses nonsynonymous and synonymous variants
      separately to allow for different penalties on them. The incorporation of
      functional annotations led to higher sensitivity and specificity levels when the
      detection results were compared with the answer sheet. The initial analysis was
      performed without knowledge of the simulating model.

PMID- 22373325
TI  - Identifying rare variants from exome scans: the GAW17 experience.
AB  - Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing
      statistical genetic methods and for developing novel methods to analyze rare
      variants that modulate complex traits. In this article, we present an overview of
      the 1000 Genomes Project exome data and simulated phenotype data that were
      distributed to GAW17 participants for analyses, the different issues addressed by
      the participants, and the process of preparation of manuscripts resulting from
      the discussions during the workshop.

PMID- 22373326
TI  - Density functional theory calculations on graphene/alpha-SiO2(0001) interface.
AB  - In this work, the graphene/alpha-SiO2(0001) interface is calculated using
      density functional theory. On the oxygen-terminated SiO2 surface, atomic
      structure reconstruction occurs at the graphene/SiO2 interface to eliminate the
      dangling bonds. The interface interaction is 77 meV/C atom, which indicates that
      van der Waals force dominates the interaction, but it is stronger than the force
      between the graphene layers in graphite. The distance between graphene and the
      SiO2 surface is 2.805 A, which is smaller than the 3.4 A interlayer distance of
      graphite. In addition, the SiO2 substrate induces p-type doping in graphene and
      opens a small gap of 0.13 eV at the Dirac point of graphene, which is desirable
      for electronic device applications.

PMID- 22373327
TI  - SPARQL assist language-neutral query composer.
AB  - BACKGROUND: SPARQL query composition is difficult for the lay-person, and even
      the experienced bioinformatician in cases where the data model is unfamiliar.
      Moreover, established best-practices and internationalization concerns dictate
      that the identifiers for ontological terms should be opaque rather than human
      readable, which further complicates the task of synthesizing queries manually.
      RESULTS: We present SPARQL Assist: a Web application that addresses these issues
      by providing context-sensitive type-ahead completion during SPARQL query
      construction. Ontological terms are suggested using their multi-lingual labels
      and descriptions, leveraging existing support for internationalization and
      language-neutrality. Moreover, the system utilizes the semantics embedded in
      ontologies, and within the query itself, to help prioritize the most likely
      suggestions. CONCLUSIONS: To ensure success, the Semantic Web must be easily
      available to all users, regardless of locale, training, or preferred language. By
      enhancing support for internationalization, and moreover by simplifying the
      manual construction of SPARQL queries through the use of controlled-natural
      language interfaces, we believe we have made some early steps towards simplifying
      access to Semantic Web resources.

PMID- 22373328
TI  - Combining effects from rare and common genetic variants in an exome-wide
      association study of sequence data.
AB  - Recent breakthroughs in next-generation sequencing technologies allow cost
      effective methods for measuring a growing list of cellular properties, including
      DNA sequence and structural variation. Next-generation sequencing has the
      potential to revolutionize complex trait genetics by directly measuring common
      and rare genetic variants within a genome-wide context. Because for a given gene
      both rare and common causal variants can coexist and have independent effects on
      a trait, strategies that model the effects of both common and rare variants could
      enhance the power of identifying disease-associated genes. To date, little work
      has been done on integrating signals from common and rare variants into powerful
      statistics for finding disease genes in genome-wide association studies. In this
      analysis of the Genetic Analysis Workshop 17 data, we evaluate various strategies
      for association of rare, common, or a combination of both rare and common
      variants on quantitative phenotypes in unrelated individuals. We show that the
      analysis of common variants only using classical approaches can achieve higher
      power to detect causal genes than recently proposed rare variant methods and that
      strategies that combine association signals derived independently in rare and
      common variants can slightly increase the power compared to strategies that focus
      on the effect of either the rare variants or the common variants.

PMID- 22373329
TI  - ADCC potency assay: increased standardization with modified lymphocytes.

PMID- 22373331
TI  - Finding genes that influence quantitative traits with tree-based clustering.
AB  - We present a new statistical method to identify genes in which one or more
      variants influence quantitative traits. We use the Genetic Analysis Workshop 17
      (GAW17) data set of unrelated individuals as a test of the method on the raw
      GAW17 phenotypes and on residuals after fitting linear models to individual-based
      covariates. By performing appropriate randomization tests, we found many
      significant results for a proportion of the genes that contain variants that
      directly contribute to disease but that have an increased type I error for
      analyses of raw phenotypes. Power calculations show that our methods have the
      ability to reliably identify a subset of the loci contributing to disease. When
      we applied our method to derived phenotypes, we removed many false positives,
      giving appropriate type I error rates at little cost to power. The correlation
      between genome-wide heterozygosity and the value of the trait Q1 appears to drive
      much of the type I error in this data set.

PMID- 22373333
TI  - Evaluation of pooled association tests for rare variant identification.
AB  - Genome-wide association studies have successfully identified many common variants
      associated with complex human diseases. However, a large portion of the remaining
      heritability cannot be explained by these common variants. Exploring rare
      variants associated with diseases is now catching more attention. Several methods
      have been recently proposed for identification of rare variants. Among them, the
      fixed-threshold, weighted-sum, and variable-threshold methods are effective in
      combining the information of multiple variants into a functional unit; these
      approaches are commonly used. We evaluate the performance of these three methods.
      Based on our analyses of the Genetic Analysis Workshop 17 data, we find that no
      method is universally better than the others. Furthermore, adjusting for
      potential covariates can not only increase the true-positive proportions but also
      reduce the false-positive proportions. Our study concludes that there is no
      uniformly most powerful test among the three methods we compared (the fixed
      threshold, weighted-sum, and variable-threshold methods), and their performances
      depend on the underlying genetic architecture of a disease.

PMID- 22373334
TI  - Comprehensive evaluation of matrix factorization methods for the analysis of DNA
      microarray gene expression data.
AB  - BACKGROUND: Clustering-based methods on gene-expression analysis have been shown
      to be useful in biomedical applications such as cancer subtype discovery. Among
      them, Matrix factorization (MF) is advantageous for clustering gene expression
      patterns from DNA microarray experiments, as it efficiently reduces the dimension
      of gene expression data. Although several MF methods have been proposed for
      clustering gene expression patterns, a systematic evaluation has not been
      reported yet. RESULTS: Here we evaluated the clustering performance of orthogonal
      and non-orthogonal MFs by a total of nine measurements for performance in four
      gene expression datasets and one well-known dataset for clustering. Specifically,
      we employed a non-orthogonal MF algorithm, BSNMF (Bi-directional Sparse Non
      negative Matrix Factorization), that applies bi-directional sparseness
      constraints superimposed on non-negative constraints, comprising a few dominantly
      co-expressed genes and samples together. Non-orthogonal MFs tended to show better
      clustering-quality and prediction-accuracy indices than orthogonal MFs as well as
      a traditional method, K-means. Moreover, BSNMF showed improved performance in
      these measurements. Non-orthogonal MFs including BSNMF showed also good
      performance in the functional enrichment test using Gene Ontology terms and
      biological pathways. CONCLUSIONS: In conclusion, the clustering performance of
      orthogonal and non-orthogonal MFs was appropriately evaluated for clustering
      microarray data by comprehensive measurements. This study showed that non
      orthogonal MFs have better performance than orthogonal MFs and K-means for
      clustering microarray data.

PMID- 22373336
TI  - DoE of fed-batch processes - model-based design and experimental evaluation.

PMID- 22373337
TI  - Disease risk prediction with rare and common variants.
AB  - A number of studies have been conducted to investigate the predictive value of
      common genetic variants for complex diseases. To date, these studies have
      generally shown that common variants have no appreciable added predictive value
      over classical risk factors. New sequencing technology has enhanced the ability
      to identify rare variants that may have larger functional effects than common
      variants. One would expect rare variants to improve the discrimination power for
      disease risk by permitting more detailed quantification of genetic risk. Using
      the Genetic Analysis Workshop 17 simulated data sets for unrelated individuals,
      we evaluate the predictive value of rare variants by comparing prediction models
      built using the support vector machine algorithm with or without rare variants.
      Empirical results suggest that rare variants have appreciable effects on disease
      risk prediction.

PMID- 22373339
TI  - Novel human partner cell line for immortalisation of rare antigen-specific B
      cells in mAb development.

PMID- 22373340
TI  - Increasing productivity of hybridoma cell lines by sorting by side scattering
      light.

PMID- 22373341
TI  - Growth characterization of CHO DP-12 cell lines with different high passage
      histories.

PMID- 22373343
TI  - Linkage analysis merging replicate phenotypes: an application to three
      quantitative phenotypes in two African samples.
AB  - We report two approaches for linkage analysis of data consisting of replicate
      phenotypes. The first approach is specifically designed for the unusual (in human
      data) replicate structure of the Genetic Analysis Workshop 17 pedigree data. The
      second approach consists of a standard linkage analysis that, although not
      specifically tailored to data consisting of replicate genotypes, was envisioned
      as providing a sounding board against which our novel approach could be assessed.
      Both approaches are applied to the analysis of three quantitative phenotypes (Q1,
      Q2, and Q4) in two sets of African families. All analyses were carried out blind
      to the generating model (i.e., the "answers"). Using both methods, we found
      numerous significant linkage signals for Q1, although population colocalization
      was absent for most of these signals. The linkage analysis of Q2 and Q4 failed to
      reveal any strong linkage signals.

PMID- 22373344
TI  - Effect of iron sources on the glycosylation macroheterogeneity of human
      recombinant IFN-gamma produced by CHO cells during batch processes.

PMID- 22373345
TI  - Reactive molecular dynamics study of chloride ion interaction with copper oxide
      surfaces in aqueous media.
AB  - Using reactive force-field (ReaxFF) and molecular dynamics simulation, we study
      atomistic scale chloride ion adsorption and transport through copper oxide thin
      films under aqueous conditions. The surface condition of passive oxide film plays
      a key role in chloride ion adsorption and facilitates initial adsorption when
      surface corrosion resistance is low. Using implemented surface defects, the
      structural evolution of the copper oxide film from thinning to breakdown is
      investigated. In addition to chemical thinning of passive film, extended defects
      in the metal substrate are observed, at high concentration of adsorbed chloride
      ions. The initial stage of breakdown is associated with rapid depletion of
      adjacent chloride ions, which creates a locally deficient environment of chloride
      ions in the solution. The dissolved copper cations gain higher charge upon
      interaction with chloride ions. Owing to the increased Coulomb interactions
      resulted from dissolved copper ions and locally low density of chloride ions, far
      field chloride ions would diffuse into the local corrosion sites, thereby
      promoting further corrosion.

PMID- 22373348
TI  - Towards rational engineering of cells: Recombinant gene expression in defined
      chromosomal loci.

PMID- 22373349
TI  - Exploration and comparison of methods for combining population- and family-based
      genetic association using the Genetic Analysis Workshop 17 mini-exome.
AB  - We examine the performance of various methods for combining family- and
      population-based genetic association data. Several approaches have been proposed
      for situations in which information is collected from both a subset of unrelated
      subjects and a subset of family members. Analyzing these samples separately is
      known to be inefficient, and it is important to determine the scenarios for which
      differing methods perform well. Others have investigated this question; however,
      no extensive simulations have been conducted, nor have these methods been applied
      to mini-exome-style data such as that provided by Genetic Analysis Workshop 17.
      We quantify the empirical power and false-positive rates for three existing
      methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare
      relative performance. We use knowledge of the underlying data simulation model to
      make these assessments.

PMID- 22373350
TI  - Synthesis and antimicrobial evaluation of new 1,4-dihydro-4-pyrazolylpyridines
      and 4-pyrazolylpyridines.
AB  - BACKGROUND: Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHP)
      have now been recognized as vital drugs. Some of these derivatives such as
      amlodipine, felodipine, isradipine, etc. have been commercialized. In view of
      wide range of biological properties associated with 1,4-DHP and owing to the
      biological importance of the oxidation step of 1,4-DHP, we carried out the
      synthesis and antimicrobial evaluation of new diethyl 1,4-dihydro-2,6-dimethyl-4
      (3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) and diethyl 2,6
      dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g).
      RESULTS: Synthesis of a series of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl
      1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) has been accomplished by
      multicomponent cyclocondensation reaction of ethyl acetoacetate, 3-aryl-1-phenyl
      pyrazole-4-carboxaldehyde (1a-g) and ammonium acetate. The dihydropyridines 2a-g
      were smoothly converted to new diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4
      pyrazolyl)pyridine-3,5-dicarboxylates (3a-g) using HTIB ([Hydroxy
      (tosyloxy)iodo]benzene, Koser's reagent) as the oxidizing agent. The
      antimicrobial studies of the title compounds, 2a-g &3a-g, are also described.

PMID- 22373351
TI  - Detection of associations with rare and common SNPs for quantitative traits: a
      nonparametric Bayes-based approach.
AB  - We propose a nonparametric Bayes-based clustering algorithm to detect
      associations with rare and common single-nucleotide polymorphisms (SNPs) for
      quantitative traits. Unlike current methods, our approach identifies associations
      with rare genetic variants at the variant level, not the gene level. In this
      method, we use a Dirichlet process prior for the distribution of SNP-specific
      regression coefficients, conduct hierarchical clustering with a distance measure
      derived from posterior pairwise probabilities of two SNPs having the same
      regression coefficient, and explore data-driven approaches to select the number
      of clusters. SNPs falling inside the largest cluster have relatively low or close
      to zero estimates of regression coefficients and are considered not associated
      with the trait. SNPs falling outside the largest cluster have relatively high
      estimates of regression coefficients and are considered potential risk variants.
      Using the data from the Genetic Analysis Workshop 17, we successfully detected
      associations with both rare and common SNPs for a quantitative trait. We conclude
      that our method provides a novel and broadly applicable strategy for obtaining
      association results with a reasonably low proportion of false discovery and that
      it can be routinely used in resequencing studies.

PMID- 22373352
TI  - Anti-idiotypic antibody Ab2/3H6 mimicking gp41: a potential HIV-1 vaccine?

PMID- 22373354
TI  - Evaluating methods for the analysis of rare variants in sequence data.
AB  - A number of rare variant statistical methods have been proposed for analysis of
      the impending wave of next-generation sequencing data. To date, there are few
      direct comparisons of these methods on real sequence data. Furthermore, there is
      a strong need for practical advice on the proper analytic strategies for rare
      variant analysis. We compare four recently proposed rare variant methods
      (combined multivariate and collapsing, weighted sum, proportion regression, and
      cumulative minor allele test) on simulated phenotype and next-generation
      sequencing data as part of Genetic Analysis Workshop 17. Overall, we find that
      all analyzed methods have serious practical limitations on identifying causal
      genes. Specifically, no method has more than a 5% true discovery rate (percentage
      of truly causal genes among all those identified as significantly associated with
      the phenotype). Further exploration shows that all methods suffer from inflated
      false-positive error rates (chance that a noncausal gene will be identified as
      associated with the phenotype) because of population stratification and gametic
      phase disequilibrium between noncausal SNPs and causal SNPs. Furthermore,
      observed true-positive rates (chance that a truly causal gene will be identified
      as significantly associated with the phenotype) for each of the four methods was
      very low (<19%). The combination of larger than anticipated false-positive rates,
      low true-positive rates, and only about 1% of all genes being causal yields poor
      discriminatory ability for all four methods. Gametic phase disequilibrium and
      population stratification are important areas for further research in the
      analysis of rare variant data.

PMID- 22373353
TI  - CD4(+) CD25(+) FoxP3(+) regulatory T cells suppress cytotoxicity of CD8(+)
      effector T cells: implications for their capacity to limit inflammatory central
      nervous system damage at the parenchymal level.
AB  - BACKGROUND: CD4(+) CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells (T reg
      cells) are known to suppress adaptive immune responses, key control tolerance and
      autoimmunity. METHODS: We challenged the role of CD4(+) T reg cells in
      suppressing established CD8(+) T effector cell responses by using the OT-I/II
      system in vitro and an OT-I-mediated, oligodendrocyte directed ex vivo model (ODC
      OVA model). RESULTS: CD4(+) T reg cells dampened cytotoxicity of an ongoing
      CD8(+) T effector cell attack in vitro and within intact central nervous system
      tissue ex vivo. However, their suppressive effect was limited by the strength of
      the antigen signal delivered to the CD8(+) T effector cells and the ratio of
      regulatory to effector T cells. CD8(+) T effector cell suppression required T
      cell receptor-mediated activation together with costimulation of CD4(+) T reg
      cells, but following activation, suppression did not require restimulation and
      was antigen non-specific. CONCLUSIONS: Our results suggest that CD4(+) T reg
      cells are capable of suppressing CD8(+) T effector cell responses at the
      parenchymal site, that is, limiting parenchymal damage in autoimmune central
      nervous system inflammation.

PMID- 22373355
TI  - HabiSign: a novel approach for comparison of metagenomes and rapid identification
      of habitat-specific sequences.
AB  - BACKGROUND: One of the primary goals of comparative metagenomic projects is to
      study the differences in the microbial communities residing in diverse
      environments. Besides providing valuable insights into the inherent structure of
      the microbial populations, these studies have potential applications in several
      important areas of medical research like disease diagnostics, detection of
      pathogenic contamination and identification of hitherto unknown pathogens. Here
      we present a novel and rapid, alignment-free method called HabiSign, which
      utilizes patterns of tetra-nucleotide usage in microbial genomes to bring out the
      differences in the composition of both diverse and related microbial communities.
      RESULTS: Validation results show that the metagenomic signatures obtained using
      the HabiSign method are able to accurately cluster metagenomes at biome,
      phenotypic and species levels, as compared to an average tetranucleotide
      frequency based approach and the recently published dinucleotide relative
      abundance based approach. More importantly, the method is able to identify
      subsets of sequences that are specific to a particular habitat. Apart from this,
      being alignment-free, the method can rapidly compare and group multiple
      metagenomic data sets in a short span of time. CONCLUSIONS: The proposed method
      is expected to have immense applicability in diverse areas of metagenomic
      research ranging from disease diagnostics and pathogen detection to bio
      prospecting. A web-server for the HabiSign algorithm is available at
      http://metagenomics.atc.tcs.com/HabiSign/.

PMID- 22373358
TI  - Neuroprotective activity of a new erythropoietin formulation with increased
      penetration in the central nervous system.

PMID- 22373359
TI  - Gauging triple stores with actual biological data.
AB  - BACKGROUND: Semantic Web technologies have been developed to overcome the
      limitations of the current Web and conventional data integration solutions. The
      Semantic Web is expected to link all the data present on the Internet instead of
      linking just documents. One of the foundations of the Semantic Web technologies
      is the knowledge representation language Resource Description Framework (RDF).
      Knowledge expressed in RDF is typically stored in so-called triple stores (also
      known as RDF stores), from which it can be retrieved with SPARQL, a language
      designed for querying RDF-based models. The Semantic Web technologies should
      allow federated queries over multiple triple stores. In this paper we compare the
      efficiency of a set of biologically relevant queries as applied to a number of
      different triple store implementations. RESULTS: Previously we developed a
      library of queries to guide the use of our knowledge base Cell Cycle Ontology
      implemented as a triple store. We have now compared the performance of these
      queries on five non-commercial triple stores: OpenLink Virtuoso (Open-Source
      Edition), Jena SDB, Jena TDB, SwiftOWLIM and 4Store. We examined three
      performance aspects: the data uploading time, the query execution time and the
      scalability. The queries we had chosen addressed diverse ontological or
      biological questions, and we found that individual store performance was quite
      query-specific. We identified three groups of queries displaying similar
      behaviour across the different stores: 1) relatively short response time queries,
      2) moderate response time queries and 3) relatively long response time queries.
      SwiftOWLIM proved to be a winner in the first group, 4Store in the second one and
      Virtuoso in the third one. CONCLUSIONS: Our analysis showed that some queries
      behaved idiosyncratically, in a triple store specific manner, mainly with
      SwiftOWLIM and 4Store. Virtuoso, as expected, displayed a very balanced
      performance - its load time and its response time for all the tested queries were
      better than average among the selected stores; it showed a very good scalability
      and a reasonable run-to-run reproducibility. Jena SDB and Jena TDB were
      consistently slower than the other three implementations. Our analysis
      demonstrated that most queries developed for Virtuoso could be successfully used
      for other implementations.

PMID- 22373360
TI  - Case-control association testing by graphical modeling for the Genetic Analysis
      Workshop 17 mini-exome sequence data.
AB  - We generalize recent work on graphical models for linkage disequilibrium to
      estimate the conditional independence structure between all variables for
      individuals in the Genetic Analysis Workshop 17 unrelated individuals data set.
      Using a stepwise approach for computational efficiency and an extension of our
      previously described methods, we estimate a model that describes the
      relationships between the disease trait, all quantitative variables, all
      covariates, ethnic origin, and the loci most strongly associated with these
      variables. We performed our analysis for the first 50 replicate data sets. We
      found that our approach was able to describe the relationships between the
      outcomes and covariates and that it could correctly detect associations of
      disease with several loci and with a reasonable false-positive detection rate.

PMID- 22373361
TI  - Se-doping dependence of the transport properties in CBE-grown InAs nanowire field
      effect transistors.
AB  - We investigated the transport properties of lateral gate field effect
      transistors (FET) that have been realized by employing, as active elements, (111)
      B-oriented InAs nanowires grown by chemical beam epitaxy with different Se-doping
      concentrations. On the basis of electrical measurements, it was found that the
      carrier mobility increases from 103 to 104 cm2/(V * sec) by varying the
      ditertiarybutyl selenide (DtBSe) precursor line pressure from 0 to 0.4 Torr,
      leading to an increase of the carrier density in the transistor channel of more
      than two orders of magnitude. By keeping the DtBSe line pressure at 0.1 Torr, the
      carrier density in the nanowire channel measures ~ 5 * 1017 cm-3 ensuring the
      best peak transconductances (> 100 mS/m) together with very low resistivity
      values (70 Omega * MUm) and capacitances in the attofarad range. These results
      are particularly relevant for further optimization of the nanowire-FET terahertz
      detectors recently demonstrated.PACS: 73.63.-b, 81.07.Gf, 85.35.-p.

PMID- 22373362
TI  - Identifying rare variants using a Bayesian regression approach.
AB  - Recent advances in next-generation sequencing technologies have made it possible
      to generate large amounts of sequence data with rare variants in a cost-effective
      way. Statistical methods that test variants individually are underpowered to
      detect rare variants, so it is desirable to perform association analysis of rare
      variants by combining the information from all variants. In this study, we use a
      Bayesian regression method to model all variants simultaneously to identify rare
      variants in a data set from Genetic Analysis Workshop 17. We studied the
      association between the quantitative risk traits Q1, Q2, and Q4 and the single
      nucleotide polymorphisms and identified several positive single-nucleotide
      polymorphisms for traits Q1 and Q2. However, the model also generated several
      apparent false positives and missed many true positives, suggesting that there is
      room for improvement in this model.

PMID- 22373363
TI  - Enriching rare variants using family-specific linkage information.
AB  - Genome-wide association studies have been successful in identifying common
      variants for common complex traits in recent years. However, common variants have
      generally failed to explain substantial proportions of the trait heritabilities.
      Rare variants, structural variations, and gene-gene and gene-environment
      interactions, among others, have been suggested as potential sources of the so
      called missing heritability. With the advent of exome-wide and whole-genome next
      generation sequencing technologies, finding rare variants in functionally
      important sites (e.g., protein-coding regions) becomes feasible. We investigate
      the role of linkage information to select families enriched for rare variants
      using the simulated Genetic Analysis Workshop 17 data. In each replicate of
      simulated phenotypes Q1 and Q2 on 697 subjects in 8 extended pedigrees, we select
      one pedigree with the largest family-specific LOD score. Across all 200
      replications, we compare the probability that rare causal alleles will be carried
      in the selected pedigree versus a randomly chosen pedigree. One example of
      successful enrichment was exhibited for gene VEGFC. The causal variant had minor
      allele frequency of 0.0717% in the simulated unrelated individuals and explained
      about 0.1% of the phenotypic variance. However, it explained 7.9% of the
      phenotypic variance in the eight simulated pedigrees and 23.8% in the family that
      carried the minor allele. The carrier's family was selected in all 200
      replications. Thus our results show that family-specific linkage information is
      useful for selecting families for sequencing, thus ensuring that rare functional
      variants are segregating in the sequencing samples.

PMID- 22373364
TI  - [3 + 2] Cycloaddition reactions of thioisatin with thiazolidine-2-carboxylic
      acid: a versatile route to new heterocyclic scaffolds.
AB  - A facile synthesis of azabicycloadducts is described by 1,3-dipolar
      cycloaddition reactions of thioisatin with thiazolidine-2-carboxylic acid in the
      presence of various electron rich and electron deficient dipolarophiles.
      Theoritical calculations have been performed to study the regioselectivity of
      products. The geometrical and energetic properties have been analyzed for the
      different reactants, transition states and cycloadducts formed.

PMID- 22373366
TI  - Application of the novel and convenient IR/MAR gene amplification technology to
      the production of recombinant protein pharmaceuticals.

PMID- 22373367
TI  - MUCHA: multiple chemical alignment algorithm to identify building block
      substructures of orphan secondary metabolites.
AB  - BACKGROUND: In contrast to the increasing number of the successful genome
      projects, there still remain many orphan metabolites for which their synthesis
      processes are unknown. Metabolites, including these orphan metabolites, can be
      classified into groups that share the same core substructures, originated from
      the same biosynthetic pathways. It is known that many metabolites are synthesized
      by adding up building blocks to existing metabolites. Therefore, it is proposed
      that, for any given group of metabolites, finding the core substructure and the
      branched substructures can help predict their biosynthetic pathway. There already
      have been many reports on the multiple graph alignment techniques to find the
      conserved chemical substructures in relatively small molecules. However, they are
      optimized for ligand binding and are not suitable for metabolomic studies.
      RESULTS: We developed an efficient multiple graph alignment method named as MUCHA
      (Multiple Chemical Alignment), specialized for finding metabolic building blocks.
      This method showed the strength in finding metabolic building blocks with
      preserving the relative positions among the substructures, which is not achieved
      by simply applying the frequent graph mining techniques. Compared with the
      combined pairwise alignments, this proposed MUCHA method generally reduced
      computational costs with improving the quality of the alignment. CONCLUSIONS:
      MUCHA successfully find building blocks of secondary metabolites, and has a
      potential to complement to other existing methods to reconstruct metabolic
      networks using reaction patterns.

PMID- 22373368
TI  - Glycan fingerprints: calculating diversity in glycan libraries.
AB  - Carbohydrate libraries printed in glycan micorarray format have had a great
      impact on the high-throughput analysis of the specificity of a wide range of
      mammalian, plant, and bacterial lectins. Chemical and chemo-enzymatic synthesis
      allows the construction of diverse glycan libraries but requires substantial
      effort and resources. To leverage the synthetic effort, the ideal library would
      be a minimal subset of all structures that provides optimal diversity. Therefore,
      a measure of library diversity is needed. To this end, we developed a linear
      representation of glycans using standard chemoinformatic tools. This
      representation was applied to measure pairwise similarity and consequently
      diversity of glycan libraries in a single value. The diversities of four existing
      sialoside glycan arrays were compared. More diverse arrays are proposed reducing
      the number of glycans. This algorithm can be applied to diverse aspects of
      library design from target structure selection to the choice of building blocks
      for their synthesis.

PMID- 22373369
TI  - Compartmentation and channelling of metabolites in the human cell line
      AGE1.HN((r)).

PMID- 22373370
TI  - High serum levels of transforming growth factor beta1 are associated with
      increased cortical thickness in cingulate and right frontal areas in healthy
      subjects.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) is a cytokine having
      multiple functions in the central nervous system such as promoting repair
      mechanisms in degenerative diseases and stroke. To date, however, its
      neuroprotective effects in non-disease conditions have not been studied METHODS:
      With the aim of exploring the relationship between peripheral TGF-beta1
      expression and brain structural integrity, 70 healthy participants underwent high
      resolution structural T1-weighted magnetic resonance imaging scans and blood
      sampling. Data were processed to obtain brain cortical thickness and serum
      concentrations of TGF-beta1. We investigated the correlation between TGF-beta1
      and cortical thickness using both region-of-interest- and vertex-based
      approaches. FINDINGS: Region-of-interest-based analysis of the cortical mantle
      showed a correlation between TGF-beta1 serum concentrations and cortical
      thickness bilaterally in cingulate and right frontal and temporal areas. Similar
      results emerged in the vertex-based analysis, where significant correlations were
      found bilaterally in cingulate and right frontal cortices. CONCLUSIONS: These
      results suggest that TGF-beta1, through its role in down-regulating inflammatory
      processes, might have a beneficial effect on the structural integrity of the
      brain in physiological states.

PMID- 22373371
TI  - Pathway-based joint effects analysis of rare genetic variants using Genetic
      Analysis Workshop 17 exon sequence data.
AB  - Pathway-based analysis has been recently used in joint tests of association
      between disease and a group of common genetic variants. Here we explore this idea
      for the joint effects analysis of rare genetic variants and their association
      with quantitative traits and disease. We accumulate multiple rare minor alleles
      in a genetic risk score for each individual in a given pathway; this score is
      then used to assess association with quantitative phenotypes and disease. We
      demonstrate that this approach may be better than studying single rare variants
      or a gene risk score for identifying individuals with significantly greater risk.

PMID- 22373372
TI  - Criteria for bioreactor comparison and operation standardisation during process
      development for mammalian cell culture.

PMID- 22373373
TI  - A LASSO-based approach to analyzing rare variants in genetic association studies.
AB  - Genetic markers with rare variants are spread out in the genome, making it
      necessary and difficult to consider them in genetic association studies.
      Consequently, wisely combining rare variants into "composite" markers may
      facilitate meaningful analyses. In this paper, we propose a novel approach of
      analyzing rare variant data by incorporating the least absolute shrinkage and
      selection operator technique. We applied this method to the Genetic Analysis
      Workshop 17 data, and our results suggest that this new approach is promising. In
      addition, we took advantage of having 200 phenotype replications and assessed the
      performance of our approach by means of repeated classification tree analyses.
      Our method and analyses were performed without knowledge of the underlying
      simulating model. Our method identified 38 markers (in 65 genes) that are
      significantly associated with the phenotype Affected and correctly identified two
      causal genes, SIRT1 and PDGFD.

PMID- 22373374
TI  - Human hair follicle equivalents in vitro for transplantation and chip-based
      substance testing.

PMID- 22373375
TI  - User centered and ontology based information retrieval system for life sciences.
AB  - BACKGROUND: Because of the increasing number of electronic resources, designing
      efficient tools to retrieve and exploit them is a major challenge. Some
      improvements have been offered by semantic Web technologies and applications
      based on domain ontologies. In life science, for instance, the Gene Ontology is
      widely exploited in genomic applications and the Medical Subject Headings is the
      basis of biomedical publications indexation and information retrieval process
      proposed by PubMed. However current search engines suffer from two main
      drawbacks: there is limited user interaction with the list of retrieved resources
      and no explanation for their adequacy to the query is provided. Users may thus be
      confused by the selection and have no idea on how to adapt their queries so that
      the results match their expectations. RESULTS: This paper describes an
      information retrieval system that relies on domain ontology to widen the set of
      relevant documents that is retrieved and that uses a graphical rendering of query
      results to favor user interactions. Semantic proximities between ontology
      concepts and aggregating models are used to assess documents adequacy with
      respect to a query. The selection of documents is displayed in a semantic map to
      provide graphical indications that make explicit to what extent they match the
      user's query; this man/machine interface favors a more interactive and iterative
      exploration of data corpus, by facilitating query concepts weighting and visual
      explanation. We illustrate the benefit of using this information retrieval system
      on two case studies one of which aiming at collecting human genes related to
      transcription factors involved in hemopoiesis pathway. CONCLUSIONS: The ontology
      based information retrieval system described in this paper (OBIRS) is freely
      available at: http://www.ontotoolkit.mines-ales.fr/ObirsClient/. This environment
      is a first step towards a user centred application in which the system enlightens
      relevant information to provide decision help.

PMID- 22373377
TI  - Application of hydrocyclones for continuous cultivation of SP-2/0 cells in
      perfusion bioreactors: Effect of hydrocyclone operating pressure.

PMID- 22373382
TI  - Use of principal components to aggregate rare variants in case-control and family
      based association studies in the presence of multiple covariates.
AB  - Rare variants may help to explain some of the missing heritability of complex
      diseases. Technological advances in next-generation sequencing give us the
      opportunity to test this hypothesis. We propose two new methods (one for case
      control studies and one for family-based studies) that combine aggregated rare
      variants and common variants located within a region through principal components
      analysis and allow for covariate adjustment. We analyzed 200 replicates
      consisting of 209 case subjects and 488 control subjects and compared the results
      to weight-based and step-up aggregation methods. The principal components and
      collapsing method showed an association between the gene FLT1 and the
      quantitative trait Q1 (P<10-30) in a fraction of the computation time of the
      other methods. The proposed family-based test has inconclusive results. The two
      methods provide a fast way to analyze simultaneously rare and common variants at
      the gene level while adjusting for covariates. However, further evaluation of the
      statistical efficiency of this approach is warranted.

PMID- 22373384
TI  - Characterization of metalloprotease and serine protease activities in batch CHO
      cell cultures: control of human recombinant IFN-gamma proteolysis by addition of
      iron citrate.

PMID- 22373385
TI  - Evaluation of a LASSO regression approach on the unrelated samples of Genetic
      Analysis Workshop 17.
AB  - The Genetic Analysis Workshop 17 data we used comprise 697 unrelated individuals
      genotyped at 24,487 single-nucleotide polymorphisms (SNPs) from a mini-exome
      scan, using real sequence data for 3,205 genes annotated by the 1000 Genomes
      Project and simulated phenotypes. We studied 200 sets of simulated phenotypes of
      trait Q2. An important feature of this data set is that most SNPs are rare, with
      87% of the SNPs having a minor allele frequency less than 0.05. For rare SNP
      detection, in this study we performed a least absolute shrinkage and selection
      operator (LASSO) regression and F tests at the gene level and calculated the
      generalized degrees of freedom to avoid any selection bias. For comparison, we
      also carried out linear regression and the collapsing method, which sums the rare
      SNPs, modified for a quantitative trait and with two different allele frequency
      thresholds. The aim of this paper is to evaluate these four approaches in this
      mini-exome data and compare their performance in terms of power and false
      positive rates. In most situations the LASSO approach is more powerful than
      linear regression and collapsing methods. We also note the difficulty in
      determining the optimal threshold for the collapsing method and the significant
      role that linkage disequilibrium plays in detecting rare causal SNPs. If a rare
      causal SNP is in strong linkage disequilibrium with a common marker in the same
      gene, power will be much improved.

PMID- 22373386
TI  - Synthesis and pharmacological characterization of potent, selective, and orally
      bioavailable isoindoline class dipeptidyl peptidase IV inhibitors.
AB  - Focused structure-activity relationships of isoindoline class DPP-IV inhibitors
      have led to the discovery of 4b as a highly selective, potent inhibitor of DPP
      IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the
      strongly active metabolite 4l in high yield, resulting in good in vivo efficacy
      for antihyperglycemic activity.

PMID- 22373387
TI  - Metalorganic chemical vapor deposition growth of InAs/GaSb type II superlattices
      with controllable AsxSb1-x interfaces.
AB  - InAs/GaSb type II superlattices were grown on (100) GaSb substrates by
      metalorganic chemical vapor deposition (MOCVD). A plane of mixed As and Sb atoms
      connecting the InAs and GaSb layers was introduced to compensate the tensile
      strain created by the InAs layer in the SL. Characterizations of the samples by
      atomic force microscopy and high-resolution X-ray diffraction demonstrate flat
      surface morphology and good crystalline quality. The lattice mismatch of
      approximately 0.18% between the SL and GaSb substrate is small compared to the
      MOCVD-grown supperlattice samples reported to date in the literature.
      Considerable optical absorption in 2- to 8-MUm infrared region has been
      realized.PACS: 78.67.Pt; 81.15.Gh; 63.22.Np; 81.05.Ea.

PMID- 22373388
TI  - Cultivation strategies of a BA/F3 cell line for fundamental cell research.

PMID- 22373389
TI  - Large-scale risk prediction applied to Genetic Analysis Workshop 17 mini-exome
      sequence data.
AB  - We consider the application of Efron's empirical Bayes classification method to
      risk prediction in a genome-wide association study using the Genetic Analysis
      Workshop 17 (GAW17) data. A major advantage of using this method is that the
      effect size distribution for the set of possible features is empirically
      estimated and that all subsequent parameter estimation and risk prediction is
      guided by this distribution. Here, we generalize Efron's method to allow for some
      of the peculiarities of the GAW17 data. In particular, we introduce two ways to
      extend Efron's model: a weighted empirical Bayes model and a joint covariance
      model that allows the model to properly incorporate the annotation information of
      single-nucleotide polymorphisms (SNPs). In the course of our analysis, we examine
      several aspects of the possible simulation model, including the identity of the
      most important genes, the differing effects of synonymous and nonsynonymous SNPs,
      and the relative roles of covariates and genes in conferring disease risk.
      Finally, we compare the three methods to each other and to other classifiers
      (random forest and neural network).

PMID- 22373390
TI  - DeviceEditor visual biological CAD canvas.
AB  - BACKGROUND: Biological Computer Aided Design (bioCAD) assists the de novo design
      and selection of existing genetic components to achieve a desired biological
      activity, as part of an integrated design-build-test cycle. To meet the emerging
      needs of Synthetic Biology, bioCAD tools must address the increasing prevalence
      of combinatorial library design, design rule specification, and scar-less multi
      part DNA assembly. RESULTS: We report the development and deployment of web-based
      bioCAD software, DeviceEditor, which provides a graphical design environment that
      mimics the intuitive visual whiteboard design process practiced in biological
      laboratories. The key innovations of DeviceEditor include visual combinatorial
      library design, direct integration with scar-less multi-part DNA assembly design
      automation, and a graphical user interface for the creation and modification of
      design specification rules. We demonstrate how biological designs are rendered on
      the DeviceEditor canvas, and we present effective visualizations of genetic
      component ordering and combinatorial variations within complex designs.
      CONCLUSIONS: DeviceEditor liberates researchers from DNA base-pair manipulation,
      and enables users to create successful prototypes using standardized, functional,
      and visual abstractions. Open and documented software interfaces support further
      integration of DeviceEditor with other bioCAD tools and software platforms.
      DeviceEditor saves researcher time and institutional resources through correct-by
      construction design, the automation of tedious tasks, design reuse, and the
      minimization of DNA assembly costs.

PMID- 22373391
TI  - Producer vs. parental cell - metabolic changes and burden upon alpha1-antitrypsin
      production in AGE1.HN((r)).

PMID- 22373392
TI  - Chromosome identification and its application in Chinese hamster ovary cells.

PMID- 22373393
TI  - Old lessons learned anew: family-based methods for detecting genes responsible
      for quantitative and qualitative traits in the Genetic Analysis Workshop 17 mini
      exome sequence data.
AB  - Family-based study designs are again becoming popular as new next-generation
      sequencing technologies make whole-exome and whole-genome sequencing projects
      economically and temporally feasible. Here we evaluate the statistical properties
      of linkage analyses and family-based tests of association for the Genetic
      Analysis Workshop 17 mini-exome sequence data. Based on our results, the linkage
      methods using relative pairs or nuclear families had low power, with the best
      results coming from variance components linkage analysis in nuclear families and
      Elston-Stewart model-based linkage analysis in extended pedigrees. For family
      based tests of association, both ASSOC and ROMP performed well for genes with
      large effects, but ROMP had the advantage of not requiring parental genotypes in
      the analysis. For the linkage analyses we conclude that genome-wide significance
      levels appear to control type I error well but that "suggestive" significance
      levels do not. Methods that make use of the extended pedigrees are well powered
      to detect major loci segregating in the families even when there is substantial
      genetic heterogeneity and the trait is mainly polygenic. However, large numbers
      of such pedigrees will be necessary to detect all major loci. The family-based
      tests of association found the same major loci as the linkage analyses and
      detected low-frequency loci with moderate effect sizes, but control of type I
      error was not as stringent.

PMID- 22373394
TI  - A protein-dependent side-chain rotamer library.
AB  - BACKGROUND: Protein side-chain packing problem has remained one of the key open
      problems in bioinformatics. The three main components of protein side-chain
      prediction methods are a rotamer library, an energy function and a search
      algorithm. Rotamer libraries summarize the existing knowledge of the
      experimentally determined structures quantitatively. Depending on how much
      contextual information is encoded, there are backbone-independent rotamer
      libraries and backbone-dependent rotamer libraries. Backbone-independent
      libraries only encode sequential information, whereas backbone-dependent
      libraries encode both sequential and locally structural information. However,
      side-chain conformations are determined by spatially local information, rather
      than sequentially local information. Since in the side-chain prediction problem,
      the backbone structure is given, spatially local information should ideally be
      encoded into the rotamer libraries. METHODS: In this paper, we propose a new type
      of backbone-dependent rotamer library, which encodes structural information of
      all the spatially neighboring residues. We call it protein-dependent rotamer
      libraries. Given any rotamer library and a protein backbone structure, we first
      model the protein structure as a Markov random field. Then the marginal
      distributions are estimated by the inference algorithms, without doing global
      optimization or search. The rotamers from the given library are then re-ranked
      and associated with the updated probabilities. RESULTS: Experimental results
      demonstrate that the proposed protein-dependent libraries significantly
      outperform the widely used backbone-dependent libraries in terms of the side
      chain prediction accuracy and the rotamer ranking ability. Furthermore, without
      global optimization/search, the side-chain prediction power of the protein
      dependent library is still comparable to the global-search-based side-chain
      prediction methods.

PMID- 22373395
TI  - Power of association tests in the presence of multiple causal variants.
AB  - We show that the statistical power of a single single-nucleotide polymorphism
      (SNP) score test for genetic association reflects the cumulative effect of all
      causal SNPs that are correlated with the test SNP. Statistical significance of a
      score test can sometimes be explained by the collective effect of weak
      correlations between the test SNP and multiple causal SNPs. In a finite
      population, weak but significant correlations between the test SNP and the causal
      SNPs can arise by chance alone. As a consequence, when a single-SNP score test
      shows significance, the causal SNPs contributing to the power of the test are not
      necessarily located near the test SNP, nor do they have to be in linkage
      disequilibrium with the test SNP. These findings are confirmed with the Genetic
      Analysis Workshop 17 mini-exome data. The findings of this study highlight the
      often overlooked importance of long-range and weak linkage disequilibrium in
      genetic association studies.

PMID- 22373396
TI  - Populous: a tool for building OWL ontologies from templates.
AB  - BACKGROUND: Ontologies are being developed for the life sciences to standardise
      the way we describe and interpret the wealth of data currently being generated.
      As more ontology based applications begin to emerge, tools are required that
      enable domain experts to contribute their knowledge to the growing pool of
      ontologies. There are many barriers that prevent domain experts engaging in the
      ontology development process and novel tools are needed to break down these
      barriers to engage a wider community of scientists. RESULTS: We present Populous,
      a tool for gathering content with which to construct an ontology. Domain experts
      need to add content, that is often repetitive in its form, but without having to
      tackle the underlying ontological representation. Populous presents users with a
      table based form in which columns are constrained to take values from particular
      ontologies. Populated tables are mapped to patterns that can then be used to
      automatically generate the ontology's content. These forms can be exported as
      spreadsheets, providing an interface that is much more familiar to many
      biologists. CONCLUSIONS: Populous's contribution is in the knowledge gathering
      stage of ontology development; it separates knowledge gathering from the
      conceptualisation and axiomatisation, as well as separating the user from the
      standard ontology authoring environments. Populous is by no means a replacement
      for standard ontology editing tools, but instead provides a useful platform for
      engaging a wider community of scientists in the mass production of ontology
      content.

PMID- 22373397
TI  - About making a CHO production cell line "research-friendly" by genetic
      engineering.

PMID- 22373398
TI  - Utilization of multifrequency permittivity measurements in addition to biomass
      monitoring.

PMID- 22373399
TI  - Stratify or adjust? Dealing with multiple populations when evaluating rare
      variants.
AB  - The unrelated individuals sample from Genetic Analysis Workshop 17 consists of a
      small number of subjects from eight population samples and genetic data composed
      mostly of rare variants. We compare two simple approaches to collapsing rare
      variants within genes for their utility in identifying genes that affect
      phenotype. We also compare results from stratified analyses to those from a
      pooled analysis that uses ethnicity as a covariate. We found that the two
      collapsing approaches were similarly effective in identifying genes that contain
      causative variants in these data. However, including population as a covariate
      was not an effective substitute for analyzing the subpopulations separately when
      only one subpopulation contained a rare variant linked to the phenotype.

PMID- 22373401
TI  - Identification of genes associated with complex traits by testing the genetic
      dissimilarity between individuals.
AB  - Using the exome sequencing data from 697 unrelated individuals and their
      simulated disease phenotypes from Genetic Analysis Workshop 17, we develop and
      apply a gene-based method to identify the relationship between a gene with
      multiple rare genetic variants and a phenotype. The method is based on the Mantel
      test, which assesses the correlation between two distance matrices using a
      permutation procedure. Using up to 100,000 permutations to estimate the
      statistical significance in 200 replicate data sets, we found that the method had
      5.1% type I error at an alpha level of 0.05 and had various power to detect genes
      with simulated genetic associations. FLT1 and KDR had the most significant
      correlations with Q1 and were replicated 170 and 24 times, respectively, in 200
      simulated data sets using a Bonferroni corrected p-value of 0.05 as a threshold.
      These results suggest that the distance correlation method can be used to
      identify genotype-phenotype association when multiple rare genetic variants in a
      gene are involved.

PMID- 22373404
TI  - Evaluating aggregate effects of rare and common variants in the 1000 Genomes
      Project exon sequencing data using latent variable structural equation modeling.
AB  - Methods that can evaluate aggregate effects of rare and common variants are
      limited. Therefore, we applied a two-stage approach to evaluate aggregate gene
      effects in the 1000 Genomes Project data, which contain 24,487 single-nucleotide
      polymorphisms (SNPs) in 697 unrelated individuals from 7 populations. In stage 1,
      we identified potentially interesting genes (PIGs) as those having at least one
      SNP meeting Bonferroni correction using univariate, multiple regression models.
      In stage 2, we evaluate aggregate PIG effects on trait, Q1, by modeling each gene
      as a latent construct, which is defined by multiple common and rare variants,
      using the multivariate statistical framework of structural equation modeling
      (SEM). In stage 1, we found that PIGs varied markedly between a randomly selected
      replicate (replicate 137) and 100 other replicates, with the exception of FLT1.
      In stage 1, collapsing rare variants decreased false positives but increased
      false negatives. In stage 2, we developed a good-fitting SEM model that included
      all nine genes simulated to affect Q1 (FLT1, KDR, ARNT, ELAV4, FLT4, HIF1A,
      HIF3A, VEGFA, VEGFC) and found that FLT1 had the largest effect on Q1 (betastd =
      0.33 +/- 0.05). Using replicate 137 estimates as population values, we found that
      the mean relative bias in the parameters (loadings, paths, residuals) and their
      standard errors across 100 replicates was on average, less than 5%. Our latent
      variable SEM approach provides a viable framework for modeling aggregate effects
      of rare and common variants in multiple genes, but more elegant methods are
      needed in stage 1 to minimize type I and type II error.

PMID- 22373400
TI  - Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after
      traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury initiates biochemical processes that lead to
      secondary neurodegeneration. Imaging studies suggest that tissue loss may
      continue for months or years after traumatic brain injury in association with
      chronic microglial activation. Recently we found that metabotropic glutamate
      receptor 5 (mGluR5) activation by (RS)-2-chloro-5-hydroxyphenylglycine (CHPG)
      decreases microglial activation and release of associated pro-inflammatory
      factors in vitro, which is mediated in part through inhibition of reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined
      whether delayed CHPG administration reduces chronic neuroinflammation and
      associated neurodegeneration after experimental traumatic brain injury in mice.
      METHODS: One month after controlled cortical impact traumatic brain injury,
      C57Bl/6 mice were randomly assigned to treatment with single dose
      intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist,
      3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract
      integrity and neurological recovery were assessed over the following three
      months. RESULTS: Traumatic brain injury resulted in mGluR5 expression in reactive
      microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG
      treatment reduced expression of reactive microglia expressing NADPH oxidase
      subunits; decreased hippocampal neuronal loss; limited lesion progression, as
      measured by repeated T2-weighted magnetic resonance imaging (at one, two and
      three months) and white matter loss, as measured by high field ex vivo diffusion
      tensor imaging at four months; and significantly improved motor and cognitive
      recovery in comparison to the other treatment groups. CONCLUSION: Markedly
      delayed, single dose treatment with CHPG significantly improves functional
      recovery and limits lesion progression after experimental traumatic brain injury,
      likely in part through actions at mGluR5 receptors that modulate
      neuroinflammation.

PMID- 22373405
TI  - A method to detect single-nucleotide polymorphisms accounting for a linkage
      signal using covariate-based affected relative pair linkage analysis.
AB  - We evaluate an approach to detect single-nucleotide polymorphisms (SNPs) that
      account for a linkage signal with covariate-based affected relative pair linkage
      analysis in a conditional-logistic model framework using all 200 replicates of
      the Genetic Analysis Workshop 17 family data set. We begin by combining the
      multiple known covariate values into a single variable, a propensity score. We
      also use each SNP as a covariate, using an additive coding based on the number of
      minor alleles. We evaluate the distribution of the difference between LOD scores
      with the propensity score covariate only and LOD scores with the propensity score
      covariate and a SNP covariate. The inclusion of causal SNPs in causal genes
      increases LOD scores more than the inclusion of noncausal SNPs either within
      causal genes or outside causal genes. We compare the results from this method to
      results from a family-based association analysis and conclude that it is possible
      to identify SNPs that account for the linkage signals from genes using a SNP
      covariate-based affected relative pair linkage approach.

PMID- 22373407
TI  - Two-stage study designs combining genome-wide association studies, tag single
      nucleotide polymorphisms, and exome sequencing: accuracy of genetic effect
      estimates.
AB  - Genome-wide association studies (GWAS) test for disease-trait associations and
      estimate effect sizes at tag single-nucleotide polymorphisms (SNPs), which
      imperfectly capture variation at causal SNPs. Sequencing studies can examine
      potential causal SNPs directly; however, sequencing the whole genome or exome can
      be prohibitively expensive. Costs can be limited by using a GWAS to detect the
      associated region(s) at tag SNPs followed by targeted sequencing to identify and
      estimate the effect size of the causal variant. Genetic effect estimates obtained
      from association studies can be inflated because of a form of selection bias
      known as the winner's curse. Conversely, estimates at tag SNPs can be attenuated
      compared to the causal SNP because of incomplete linkage disequilibrium. These
      two effects oppose each other. Analysis of rare SNPs further complicates our
      understanding of the winner's curse because rare SNPs are difficult to tag and
      analysis can involve collapsing over multiple rare variants. In two-stage
      analysis of Genetic Analysis Workshop 17 simulated data sets, we find that
      selection at the tag SNP produces upward bias in the estimate of effect at the
      causal SNP, even when the tag and causal SNPs are not well correlated. The bias
      similarly carries through to effect estimates for rare variant summary measures.
      Replication studies designed with sample sizes computed using biased estimates
      will be under-powered to detect a disease-causing variant. Accounting for bias in
      the original study is critical to avoid discarding disease-associated SNPs at
      follow up.

PMID- 22373408
TI  - In vitro microbiological evaluation of 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H
      pyrazole-5,1-(4H,5H)-diyl))diethanones, novel bisacetylated pyrazoles.
AB  - Novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)
      diyl))diethanones 7-12 were tested for their antimicrobial activity by disc
      diffusion and twofold serial dilution method against the tested bacterial and
      fungal strains. Compounds 7 against Micrococcus luteus, 8 against beta-Heamolytic
      streptococcus, M. luteus, Klebsiella pneumonia, Microsporum gypseum, 9 against
      Staphylococcus aureus, Shigella flexneri, Vibreo cholerae, Pseudomonas
      aeruginosa, Aspergillus flavus, Mucor indicus, 10 against Salmonella typhii, S.
      flexneri, M. gypseum, 11 against K. pneumonia, M. gypseum, 12 against K.
      pneumonia, and M. gypseum show superior zone of inhibitions and exhibited
      excellent antibacterial and antifungal activities at a MIC value of 6.25 MUg/mL.
      Moreover, all the tested compounds 7-12 revealed promising antitubercular
      activity against Mycobacterium tuberculosis H37Rv and INH-resistant M.
      tuberculosis. Compounds 8 against M. tuberculosis and 11 against INH-resistant M.
      tuberculosis exhibited the percentage of reduction in RLU at 89 and 85%,
      respectively.

PMID- 22373409
TI  - Exploring and linking biomedical resources through multidimensional semantic
      spaces.
AB  - BACKGROUND: The semantic integration of biomedical resources is still a
      challenging issue which is required for effective information processing and data
      analysis. The availability of comprehensive knowledge resources such as
      biomedical ontologies and integrated thesauri greatly facilitates this
      integration effort by means of semantic annotation, which allows disparate data
      formats and contents to be expressed under a common semantic space. In this
      paper, we propose a multidimensional representation for such a semantic space,
      where dimensions regard the different perspectives in biomedical research (e.g.,
      population, disease, anatomy and protein/genes). RESULTS: This paper presents a
      novel method for building multidimensional semantic spaces from semantically
      annotated biomedical data collections. This method consists of two main
      processes: knowledge and data normalization. The former one arranges the concepts
      provided by a reference knowledge resource (e.g., biomedical ontologies and
      thesauri) into a set of hierarchical dimensions for analysis purposes. The latter
      one reduces the annotation set associated to each collection item into a set of
      points of the multidimensional space. Additionally, we have developed a visual
      tool, called 3D-Browser, which implements OLAP-like operators over the generated
      multidimensional space. The method and the tool have been tested and evaluated in
      the context of the Health-e-Child (HeC) project. Automatic semantic annotation
      was applied to tag three collections of abstracts taken from PubMed, one for each
      target disease of the project, the Uniprot database, and the HeC patient record
      database. We adopted the UMLS Meta-thesaurus 2010AA as the reference knowledge
      resource. CONCLUSIONS: Current knowledge resources and semantic-aware technology
      make possible the integration of biomedical resources. Such an integration is
      performed through semantic annotation of the intended biomedical data resources.
      This paper shows how these annotations can be exploited for integration,
      exploration, and analysis tasks. Results over a real scenario demonstrate the
      viability and usefulness of the approach, as well as the quality of the generated
      multidimensional semantic spaces.

PMID- 22373410
TI  - Improving volumetric productivity of a stable human CAP cell line by bioprocess
      optimization.

PMID- 22373411
TI  - Isolation of active peptides from plant hydrolysates that promote Vero cells
      growth in stirred cultures.

PMID- 22373412
TI  - Identifying influential regions in extremely rare variants using a fixed-bin
      approach.
AB  - In this study, we analyze the Genetic Analysis Workshop 17 data to identify
      regions of single-nucleotide polymorphisms (SNPs) that exhibit a significant
      influence on response rate (proportion of subjects with an affirmative affected
      status), called the affected ratio, among rare variants. Under the null
      hypothesis, the distribution of rare variants is assumed to be uniform over case
      (affected) and control (unaffected) subjects. We attempt to pinpoint regions
      where the composition is significantly different between case and control events,
      specifically where there are unusually high numbers of rare variants among
      affected subjects. We focus on private variants, which require a degree of
      "collapsing" to combine information over several SNPs, to obtain meaningful
      results. Instead of implementing a gene-based approach, where regions would vary
      in size and sometimes be too small to achieve a strong enough signal, we
      implement a fixed-bin approach, with a preset number of SNPs per region, relying
      on the assumption that proximity and similarity go hand in hand. Through
      application of 100-SNP and 30-SNP fixed bins, we identify several most
      influential regions, which later are seen to contain some of the causal SNPs. The
      100- and 30-SNP approaches detected seven and three causal SNPs among the most
      significant regions, respectively, with two overlapping SNPs located in the
      ELAVL4 gene, reported by both procedures.

PMID- 22373414
TI  - CHO cell lines generated by PiggyBac transposition.

PMID- 22373413
TI  - Dipeptidyl peptidase IV, aminopeptidase N and DPIV/APN-like proteases in cerebral
      ischemia.
AB  - BACKGROUND: Cerebral inflammation is a hallmark of neuronal degeneration.
      Dipeptidyl peptidase IV, aminopeptidase N as well as the dipeptidyl peptidases
      II, 8 and 9 and cytosolic alanyl-aminopeptidase are involved in the regulation of
      autoimmunity and inflammation. We studied the expression, localisation and
      activity patterns of these proteases after endothelin-induced occlusion of the
      middle cerebral artery in rats, a model of transient and unilateral cerebral
      ischemia. METHODS: Male Sprague-Dawley rats were used. RT-PCR,
      immunohistochemistry and protease activity assays were performed at different
      time points, lasting from 2 h to 7 days after cerebral ischemia. The effect of
      protease inhibitors on ischemia-dependent infarct volumes was quantified 7 days
      post middle cerebral artery occlusion. Statistical analysis was conducted using
      the t-test. RESULTS: Qualitative RT-PCR revealed these proteases in ipsilateral
      and contralateral cortices. Dipeptidyl peptidase II and aminopeptidase N were up
      regulated ipsilaterally from 6 h to 7 days post ischemia, whereas dipeptidyl
      peptidase 9 and cytosolic alanyl-aminopeptidase were transiently down-regulated
      at day 3. Dipeptidyl peptidase 8 and aminopeptidase N immunoreactivities were
      detected in cortical neurons of the contralateral hemisphere. At the same time
      point, dipeptidyl peptidase IV, 8 and aminopeptidase N were identified in
      activated microglia and macrophages in the ipsilateral cortex. Seven days post
      artery occlusion, dipeptidyl peptidase IV immunoreactivity was found in the
      perikarya of surviving cortical neurons of the ipsilateral hemisphere, whereas
      their nuclei were dipeptidyl peptidase 8- and amino peptidase N-positive. At the
      same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N were targeted in
      astroglial cells. Total dipeptidyl peptidase IV, 8 and 9 activities remained
      constant in both hemispheres until day 3 post experimental ischemia, but were
      increased (+165%) in the ipsilateral cortex at day 7. In parallel, aminopeptidase
      N and cytosolic alanyl-aminopeptidase activities remained unchanged. CONCLUSIONS:
      Distinct expression, localization and activity patterns of proline- and alanine
      specific proteases indicate their involvement in ischemia-triggered inflammation
      and neurodegeneration. Consistently, IPC1755, a non-selective protease inhibitor,
      revealed a significant reduction of cortical lesions after transient cerebral
      ischemia and may suggest dipeptidyl peptidase IV, aminopeptidase N and proteases
      with similar substrate specificity as potentially therapy-relevant targets.

PMID- 22373415
TI  - Analysis of the mitochondrial subproteome of the human cell line AGE1.HN - a
      contribution to a systems biology approach.

PMID- 22373417
TI  - Optimizing de novo transcriptome assembly from short-read RNA-Seq data: a
      comparative study.
AB  - BACKGROUND: With the fast advances in nextgen sequencing technology, high
      throughput RNA sequencing has emerged as a powerful and cost-effective way for
      transcriptome study. De novo assembly of transcripts provides an important
      solution to transcriptome analysis for organisms with no reference genome.
      However, there lacked understanding on how the different variables affected
      assembly outcomes, and there was no consensus on how to approach an optimal
      solution by selecting software tool and suitable strategy based on the properties
      of RNA-Seq data. RESULTS: To reveal the performance of different programs for
      transcriptome assembly, this work analyzed some important factors, including k
      mer values, genome complexity, coverage depth, directional reads, etc. Seven
      program conditions, four single k-mer assemblers (SK: SOAPdenovo, ABySS, Oases
      and Trinity) and three multiple k-mer methods (MK: SOAPdenovo-MK, trans-ABySS and
      Oases-MK) were tested. While small and large k-mer values performed better for
      reconstructing lowly and highly expressed transcripts, respectively, MK strategy
      worked well for almost all ranges of expression quintiles. Among SK tools,
      Trinity performed well across various conditions but took the longest running
      time. Oases consumed the most memory whereas SOAPdenovo required the shortest
      runtime but worked poorly to reconstruct full-length CDS. ABySS showed some good
      balance between resource usage and quality of assemblies. CONCLUSIONS: Our work
      compared the performance of publicly available transcriptome assemblers, and
      analyzed important factors affecting de novo assembly. Some practical guidelines
      for transcript reconstruction from short-read RNA-Seq data were proposed. De novo
      assembly of C. sinensis transcriptome was greatly improved using some optimized
      methods.

PMID- 22373418
TI  - Novel tree-based method to generate markers from rare variant data.
AB  - Existing methods for analyzing rare variant data focus on collapsing a group of
      rare variants into a single common variant; collapsing is based on an intuitive
      function of the rare variant genotype information, such as an indicator function
      or a weighted sum. It is more natural, however, to take into account the single
      nucleotide polymorphism (SNP) interactions informed directly by the data. We
      propose a novel tree-based method that automatically detects SNP interactions and
      generates candidate markers from the original pool of rare variants. In addition,
      we utilize the advantage of having 200 phenotype replications in the Genetic
      Analysis Workshop 17 data to assess the candidate markers by means of repeated
      logistic regressions. This new approach shows potential in the rare variant
      analysis. We correctly identify the association between gene FLT1 and phenotype
      Affect, although there exist other false positives in our results. Our analyses
      are performed without knowledge of the underlying simulating model.

PMID- 22373419
TI  - Physical methods for synchronization of a human production cell line.

PMID- 22373420
TI  - Development of an automated, multiwell plate based screening system for
      suspension cell culture.

PMID- 22373423
TI  - Optimization of a synthetic mixture composed of major Trichoderma reesei enzymes
      for the hydrolysis of steam-exploded wheat straw.
AB  - BACKGROUND: An efficient hydrolysis of lignocellulosic substrates to soluble
      sugars for biofuel production necessitates the interplay and synergistic
      interaction of multiple enzymes. An optimized enzyme mixture is crucial for
      reduced cost of the enzymatic hydrolysis step in a bioethanol production process
      and its composition will depend on the substrate and type of pretreatment used.
      In the present study, an experimental design was used to determine the optimal
      composition of a Trichoderma reesei enzyme mixture, comprising the main cellulase
      and hemicellulase activities, for the hydrolysis of steam-exploded wheat straw.
      METHODS: Six enzymes, CBH1 (Cel7a), CBH2 (Cel6a), EG1 (Cel7b), EG2 (Cel5a), as
      well as the xyloglucanase Cel74a and the xylanase XYN1 (Xyl11a) were purified
      from a T. reesei culture under lactose/xylose-induced conditions. Sugar release
      was followed in milliliter-scale hydrolysis assays for 48 hours and the influence
      of the mixture on initial conversion rates and final yields is assessed. RESULTS:
      The developed model could show that both responses were strongly correlated.
      Model predictions suggest that optimal hydrolysis yields can be obtained over a
      wide range of CBH1 to CBH2 ratios, but necessitates a high proportion of EG1 (13%
      to 25%) which cannot be replaced by EG2. Whereas 5% to 10% of the latter enzyme
      and a xylanase content above 6% are required for highest yields, these enzymes
      are predicted to be less important in the initial stage of hydrolysis.
      CONCLUSIONS: The developed model could reliably predict hydrolysis yields of
      enzyme mixtures in the studied domain and highlighted the importance of the
      respective enzyme components in both the initial and the final hydrolysis phase
      of steam-exploded wheat straw.

PMID- 22373425
TI  - Application of collapsing methods for continuous traits to the Genetic Analysis
      Workshop 17 exome sequence data.
AB  - Genetic Analysis Workshop 17 used real sequence data from the 1000 Genomes
      Project and simulated phenotypes influenced by a large number of rare variants.
      Our aim is to evaluate the performance of various collapsing methods that were
      developed for analysis of multiple rare variants. We apply collapsing methods to
      continuous phenotypes Q1 and Q2 for all 200 replicates of the unrelated
      individuals data. Within each gene, we collapse (1) all SNPs, (2) all SNPs with
      minor allele frequency (MAF) < 0.05, and (3) nonsynonymous SNPs with MAF < 0.05.
      We consider two tests when collapsing variants: using the proportion of variants
      and using the presence/absence of any variant. We also compare our results to a
      single-marker analysis using PLINK. For phenotype Q1, the proportion test for
      collapsing rare nonsynonymous SNPs often performed the best. Two genes (FLT1 and
      KDR) had statistically significant results. A single-marker analysis using PLINK
      also provided statistically significant results for some SNPs within these two
      genes. For phenotype Q2, collapsing rare nonsynonymous SNPs performed the best,
      with almost no difference between proportion and presence tests. However, neither
      collapsing methods nor a single-marker analysis provided statistically
      significant results at the true genes for Q2. We also found that a large number
      of noncausal genes had high correlations with causal genes for Q1 and Q2, which
      may account for inflated false positives.

PMID- 22373422
TI  - Comparative studies on single-layer reduced graphene oxide films obtained by
      electrochemical reduction and hydrazine vapor reduction.
AB  - The comparison between two kinds of single-layer reduced graphene oxide (rGO)
      sheets, obtained by reduction of graphene oxide (GO) with the electrochemical
      method and hydrazine vapor reduction, referred to as E-rGO and C-rGO,
      respectively, is systematically studied. Although there is no morphology
      difference between the E-rGO and C-rGO films adsorbed on solid substrates
      observed by AFM, the reduction process to obtain the E-rGO and C-rGO films is
      quite different. In the hydrazine vapor reduction, the nitrogen element is
      incorporated into the obtained C-rGO film, while no additional element is
      introduced to the E-rGO film during the electrochemical reduction. Moreover,
      Raman spectra show that the electrochemical method is more effective than the
      hydrazine vapor reduction method to reduce the GO films. In addition, E-rGO shows
      better electrocatalysis towards dopamine than does C-rGO. This study is helpful
      for researchers to understand these two different reduction methods and choose a
      suitable one to reduce GO based on their experimental requirements.

PMID- 22373426
TI  - CAP-T cell expression system: a novel rapid and versatile human cell expression
      system for fast and high yield transient protein expression.

PMID- 22373429
TI  - Evaluating methods for combining rare variant data in pathway-based tests of
      genetic association.
AB  - Analyzing sets of genes in genome-wide association studies is a relatively new
      approach that aims to capitalize on biological knowledge about the interactions
      of genes in biological pathways. This approach, called pathway analysis or gene
      set analysis, has not yet been applied to the analysis of rare variants. Applying
      pathway analysis to rare variants offers two competing approaches. In the first
      approach rare variant statistics are used to generate p-values for each gene
      (e.g., combined multivariate collapsing [CMC] or weighted-sum [WS]) and the gene
      level p-values are combined using standard pathway analysis methods (e.g., gene
      set enrichment analysis or Fisher's combined probability method). In the second
      approach, rare variant methods (e.g., CMC and WS) are applied directly to sets of
      single-nucleotide polymorphisms (SNPs) representing all SNPs within genes in a
      pathway. In this paper we use simulated phenotype and real next-generation
      sequencing data from Genetic Analysis Workshop 17 to analyze sets of rare
      variants using these two competing approaches. The initial results suggest
      substantial differences in the methods, with Fisher's combined probability method
      and the direct application of the WS method yielding the best power. Evidence
      suggests that the WS method works well in most situations, although Fisher's
      method was more likely to be optimal when the number of causal SNPs in the set
      was low but the risk of the causal SNPs was high.

PMID- 22373430
TI  - Bismuth nitrate pentahydrate-induced novel nitration of eugenol.
AB  - BACKGROUND: Eugenol, the main constituent of clove oil possesses a number of
      medicinal activities. To enhance the medicinal property, structural modification
      is required. On the other hand, bismuth nitrate pentahydrate has been established
      as an excellent eco-friendly nitrating agent for several classes of organic
      compounds. RESULTS: Bismuth nitrate pentahydrate-induced nitration of eugenol has
      been investigated very thoroughly. Twenty five different conditions have been
      studied. The microwave-induced solvent-free reaction has been identified as the
      best condition. CONCLUSIONS: Spectral analyses confirm that 5-nitroeugenol is the
      sole product in all the cases. No oxidized or isomerized product could be
      detected.

PMID- 22373431
TI  - Development of a triculture based system for improved benefit/risk assessment in
      pharmacology and human food.

PMID- 22373433
TI  - A pathway-based association analysis model using common and rare variants.
AB  - How various genetic effects in combination affect susceptibility to certain
      disease states continues to be a major area of methodological research. Various
      rare variant models have been proposed, in response to a common failure to either
      identify or validate biologically driven causal genetic variants in genome-wide
      association studies. Adopting the idea that multiple rare variants may
      effectively produce a combined effect equal to a single common variant effect
      through common linkage with this variant, we construct a pathway-based genetic
      association analysis model using both common and rare variants. This genetic
      model is applied to the disease status of unrelated individuals in replication 1
      from Genetic Analysis Workshop 17. In this simulated example, we were able to
      identify several pathways that were potentially associated with the disease
      status and found that common variants showed stronger genetic effect than rare
      variants.

PMID- 22373436
TI  - Gene-based Higher Criticism methods for large-scale exonic single-nucleotide
      polymorphism data.
AB  - In genome-wide association studies, gene-based methods measure potential joint
      genetic effects of loci within genes and are promising for detecting causative
      genetic variations. Following recent theoretical research in statistical multiple
      hypothesis testing, we propose to adapt the Higher Criticism procedures to
      develop novel gene-based methods that use the information of linkage
      disequilibrium for detecting weak and sparse genetic signals. With the large
      scale exonic single-nucleotide polymorphism data from Genetic Analysis Workshop
      17, we show that the new Higher-Criticism-type gene-based methods have higher
      statistical power to detect causative genes than the minimal P-value method,
      ridge regression, and the prototypes of Higher Criticism do.

PMID- 22373435
TI  - Prenatal diagnosis of Wolf-Hirschhorn syndrome confirmed by comparative genomic
      hybridization array: report of two cases and review of the literature.
AB  - Wolf-Hirschhorn syndrome (WHS) is a well known genetic condition caused by a
      partial deletion of the short arm of chromosome 4. The great variability in the
      extent of the 4p deletion and the possible contribution of additional genetic
      rearrangements lead to a wide spectrum of clinical manifestations. The majority
      of the reports of prenatally diagnosed WHS cases are associated with large 4p
      deletions identified by conventional chromosome analysis; however, the widespread
      clinical use of novel molecular techniques such as array comparative genomic
      hybridization (a-CGH) has increased the detection rate of submicroscopic
      chromosomal aberrations associated with WHS phenotype. We provide a report of two
      fetuses with WHS presenting with intrauterine growth restriction as an isolated
      finding or combined with oligohydramnios and abnormal Doppler waveform in
      umbilical artery and uterine arteries. Standard karyotyping demonstrated a
      deletion on chromosome 4 in both cases [del(4)(p15.33) and del(4)(p15.31),
      respectively] and further application of a-CGH confirmed the diagnosis and
      offered a precise characterization of the genetic defect. A detailed review of
      the currently available literature on the prenatal diagnostic approach of WHS in
      terms of fetal sonographic assessment and molecular cytogenetic investigation is
      also provided.

PMID- 22373437
TI  - Identification of functional genetic variation in exome sequence analysis.
AB  - Recent technological advances have allowed us to study individual genomes at a
      base-pair resolution and have demonstrated that the average exome harbors more
      than 15,000 genetic variants. However, our ability to understand the biological
      significance of the identified variants and to connect these observed variants
      with phenotypes is limited. The first step in this process is to identify genetic
      variation that is likely to result in changes to protein structure and function,
      because detailed studies, either population based or functional, for each of the
      identified variants are not practicable. Therefore algorithms that yield valid
      predictions of a variant's functional significance are needed. Over the past
      decade, several programs have been developed to predict the probability that an
      observed sequence variant will have a deleterious effect on protein function.
      These algorithms range from empirical programs that classify using known
      biochemical properties to statistical algorithms trained using a variety of data
      sources, including sequence conservation data, biochemical properties, and
      functional data. Using data from the pilot3 study of the 1000 Genomes Project
      available through Genetic Analysis Workshop 17, we compared the results of four
      programs (SIFT, PolyPhen, MAPP, and VarioWatch) used to predict the functional
      relevance of variants in 101 genes. Analysis was conducted without knowledge of
      the simulation model. Agreement between programs was modest ranging from 59.4% to
      71.4% and only 3.5% of variants were classified as deleterious and 10.9% as
      tolerated across all four programs.

PMID- 22373439
TI  - Transposon mediated co-integration and co-expression of transgenes in CHO-DG44
      cells.

PMID- 22373440
TI  - Production and purification of TGFb-1 in CHO-Cells.

PMID- 22373441
TI  - Enumerating tree-like chemical graphs with given upper and lower bounds on path
      frequencies.
AB  - BACKGROUND: Enumeration of chemical graphs satisfying given constraints is one of
      the fundamental problems in chemoinformatics and bioinformatics since it leads to
      a variety of useful applications including structure determination of novel
      chemical compounds and drug design. RESULTS: In this paper, we consider the
      problem of enumerating all tree-like chemical graphs from a given set of feature
      vectors, which is specified by a pair of upper and lower feature vectors, where a
      feature vector represents the frequency of prescribed paths in a chemical
      compound to be constructed. This problem can be solved by applying the algorithm
      proposed by Ishida et al. to each single feature vector in the given set, but
      this method may take much computation time because in general there are many
      feature vectors in a given set. We propose a new exact branch-and-bound algorithm
      for the problem so that all the feature vectors in a given set are handled
      directly. Since we cannot use the bounding operation proposed by Ishida et al.
      due to upper and lower constraints, we introduce new bounding operations based on
      upper and lower feature vectors, a bond constraint, and a detachment condition.
      CONCLUSIONS: Our proposed algorithm is useful for enumerating tree-like chemical
      graphs with given upper and lower bounds on path frequencies.

PMID- 22373442
TI  - Comparison of different membrane supports for monolayer culture of bovine oviduct
      epithelial cells.

PMID- 22373443
TI  - Analytical techniques for characterization of raw materials in cell culture
      media.
AB  - Raw materials are a critical part of any cell culture medium; therefore, it is of
      utmost importance to understand and characterize them for high-quality product.
      The raw material characterization (RMC) program at SAFC focuses on individual
      screening of raw materials both analytically and biologically. The goal of the
      program is to develop the best-in-class knowledge base of the raw materials used
      in SAFC's media formulations and their impact on performance of products. 

PMID- 22373444
TI  - Characterisation of cultivation of the human cell line AGE1.HN.AAT.

PMID- 22373445
TI  - Identification of multiple rare variants associated with a disease.
AB  - Identifying rare variants that are responsible for complex disease has been
      promoted by advances in sequencing technologies. However, statistical methods
      that can handle the vast amount of data generated and that can interpret the
      complicated relationship between disease and these variants have lagged. We apply
      a zero-inflated Poisson regression model to take into account the excess of zeros
      caused by the extremely low frequency of the 24,487 exonic variants in the
      Genetic Analysis Workshop 17 data. We grouped the 697 subjects in the data set as
      Europeans, Asians, and Africans based on principal components analysis and found
      the total number of rare variants per gene for each individual. We then analyzed
      these collapsed variants based on the assumption that rare variants are enriched
      in a group of people affected by a disease compared to a group of unaffected
      people. We also tested the hypothesis with quantitative traits Q1, Q2, and Q4.
      Analyses performed on the combined 697 individuals and on each ethnic group
      yielded different results. For the combined population analysis, we found that
      UGT1A1, which was not part of the simulation model, was associated with disease
      liability and that FLT1, which was a causal locus in the simulation model, was
      associated with Q1. Of the causal loci in the simulation models, FLT1 and KDR
      were associated with Q1 and VNN1 was correlated with Q2. No significant genes
      were associated with Q4. These results show the feasibility and capability of our
      new statistical model to detect multiple rare variants influencing disease risk.

PMID- 22373446
TI  - A junctionless SONOS nonvolatile memory device constructed with in situ-doped
      polycrystalline silicon nanowires.
AB  - In this paper, a silicon-oxide-nitride-silicon nonvolatile memory constructed on
      an n+-poly-Si nanowire [NW] structure featuring a junctionless [JL] configuration
      is presented. The JL structure is fulfilled by employing only one in situ heavily
      phosphorous-doped poly-Si layer to simultaneously serve as source/drain regions
      and NW channels, thus greatly simplifying the manufacturing process and
      alleviating the requirement of precise control of the doping profile. Owing to
      the higher carrier concentration in the channel, the developed JL NW device
      exhibits significantly enhanced programming speed and larger memory window than
      its counterpart with conventional undoped-NW-channel. Moreover, it also displays
      acceptable erase and data retention properties. Hence, the desirable memory
      characteristics along with the much simplified fabrication process make the JL NW
      memory structure a promising candidate for future system-on-panel and three
      dimensional ultrahigh density memory applications.

PMID- 22373450
TI  - Improvement of cell freezing technologies: towards a fully closed process.

PMID- 22373449
TI  - Pathology of porcine peripheral white blood cells during infection with African
      swine fever virus.
AB  - BACKGROUND: African swine fever virus (ASFV) is the causative agent of African
      swine fever (ASF) that is the significant disease of domestic pigs. Several
      studies showed that ASFV can influence on porcine blood cells in vitro. Thus, we
      asked ourselves whether ASFV infection results in changes in porcine blood cells
      in vivo. A series of experiments were performed in order to investigate the
      effects of ASFV infection on porcine peripheral white blood cells. Nine pigs were
      inoculated by intramuscular injection with 104 50% hemadsorbing doses of virus
      (genotype II) distributed in Armenia and Georgia. The total number of fifteen
      cell types was calculated during experimental infection. RESULTS: Although band
      to-segmented neutrophils ratio became much higher (3.5) in infected pigs than in
      control group (0.3), marked neutropenia and lymphopenia were detected from 2 to 3
      days post-infection. In addition to band neutrophils, the high number of other
      immature white blood cells, such as metamyelocytes, was observed during the
      course of infection. From the beginning of infection, atypical lymphocytes, with
      altered nuclear shape, arose and became 15% of total cells in the final phase of
      infection. Image scanning cytometry revealed hyperdiploid DNA content in atypical
      lymphocytes only from 5 days post-infection, indicating that DNA synthesis in
      pathological lymphocytes occurred in the later stages of infection. CONCLUSION:
      From this study, it can be concluded that ASFV infection leads to serious changes
      in composition of white blood cells. Particularly, acute ASFV infection in vivo
      is accompanied with the emergence of immature cells and atypical lymphocytes in
      the host blood. The mechanisms underlying atypical cell formation remain to be
      elucidated.

PMID- 22373451
TI  - Challenges and directions: an analysis of Genetic Analysis Workshop 17 data by
      collapsing rare variants within family data.
AB  - Recent studies suggest that the traditional case-control study design does not
      have sufficient power to discover rare risk variants. Two different methods
      collapsing and family data-are suggested as alternatives for discovering these
      rare variants. Compared with common variants, rare variants have unique
      characteristics. In this paper, we assess the distribution of rare variants in
      family data. We notice that a large number of rare variants exist only in one or
      two families and that the association result is largely shaped by those families.
      Therefore we explore the possibility of integrating both the collapsing method
      and the family data method. This combinational approach offers a potential power
      boost for certain causal genes, including VEGFA, VEGFC, SIRT1, SREBF1, PIK3R3,
      VLDLR, PLAT, and FLT4, and thus deserves further investigation.

PMID- 22373453
TI  - Daphnane diterpene hirsein B downregulates melanogenesis in B16 murine melanoma
      cells by cAMP pathway inhibition.

PMID- 22373454
TI  - Comparison of scoring methods for the detection of causal genes with or without
      rare variants.
AB  - Rare causal variants are believed to significantly contribute to the genetic
      basis of common diseases or quantitative traits. Appropriate statistical methods
      are required to discover the highest possible number of disease-relevant variants
      in a genome-wide screening study. The publicly available Genetic Analysis
      Workshop 17 data set consists of 697 individuals and 24,487 genetic variants. It
      includes a simulated complex disease model with intermediate quantitative
      phenotypes. We compare four gene-wise scoring methods with respect to ranking of
      causal genes under variable allele frequency thresholds for collapsing of rare
      variants and considering whether or not rare variants were included. We also
      compare causal genes for which the ranks differ clearly between scoring methods
      regarding such characteristics as number and strength of causal variants. We
      corroborated our findings with additional simulations. We found that the maximum
      statistics method was superior in assigning high ranks to genes with a single
      strong causal variant. Hotelling's T2 test was superior for genes with several
      independent causal variants. This was consistent for all phenotypes and was
      confirmed by single-gene analyses and additional simulations. The multivariate
      analysis performed similarly to Hotelling's T2 test. The least absolute shrinkage
      and selection operator (LASSO) analysis was widely comparable with the maximum
      statistics method. We conclude that the maximum statistics method is a superior
      alternative to Hotelling's T2 test if one expects only one independent causal
      variant per gene with a dominating effect. Such a variant could also be a
      supermarker derived by collapsing rare variants. Because the true nature of the
      genetic effect is unknown for real data, both methods need to be taken into
      consideration.

PMID- 22373455
TI  - Efficient computation of spaced seeds.
AB  - BACKGROUND: The most frequently used tools in bioinformatics are those searching
      for similarities, or local alignments, between biological sequences. Since the
      exact dynamic programming algorithm is quadratic, linear-time heuristics such as
      BLAST are used. Spaced seeds are much more sensitive than the consecutive seed of
      BLAST and using several seeds represents the current state of the art in
      approximate search for biological sequences. The most important aspect is
      computing highly sensitive seeds. Since the problem seems hard, heuristic
      algorithms are used. The leading software in the common Bernoulli model is the
      SpEED program. FINDINGS: SpEED uses a hill climbing method based on the overlap
      complexity heuristic. We propose a new algorithm for this heuristic that improves
      its speed by over one order of magnitude. We use the new implementation to
      compute improved seeds for several software programs. We compute as well multiple
      seeds of the same weight as MegaBLAST, that greatly improve its sensitivity.
      CONCLUSION: Multiple spaced seeds are being successfully used in bioinformatics
      software programs. Enabling researchers to compute very fast high quality seeds
      will help expanding the range of their applications.

PMID- 22373457
TI  - Principal components ancestry adjustment for Genetic Analysis Workshop 17 data.
AB  - Statistical tests on rare variant data may well have type I error rates that
      differ from their nominal levels. Here, we use the Genetic Analysis Workshop 17
      data to estimate type I error rates and powers of three models for identifying
      rare variants associated with a phenotype: (1) by using the number of minor
      alleles, age, and smoking status as predictor variables; (2) by using the number
      of minor alleles, age, smoking status, and the identity of the population of the
      subject as predictor variables; and (3) by using the number of minor alleles,
      age, smoking status, and ancestry adjustment using 10 principal component scores.
      We studied both quantitative phenotype and a dichotomized phenotype. The model
      with principal component adjustment has type I error rates that are closer to the
      nominal level of significance of 0.05 for single-nucleotide polymorphisms (SNPs)
      in noncausal genes for the selected phenotype than the model directly adjusting
      for population. The principal component adjustment model type I error rates are
      also closer to the nominal level of 0.05 for noncausal SNPs located in causal
      genes for the phenotype. The power for causal SNPs with the principal component
      adjustment model is comparable to the power of the other methods. The power using
      the underlying quantitative phenotype is greater than the power using the
      dichotomized phenotype.

PMID- 22373459
TI  - Commentary on "Oncologists' and physiatrists' attitudes regarding rehabilitation
      for patients with advanced cancer".

PMID- 22373458
TI  - Oncologists' and physiatrists' attitudes regarding rehabilitation for patients
      with advanced cancer.
AB  - OBJECTIVE: To determine whether differences in attitude and practice between
      physiatrists and oncologists exist that may be barriers to patients with advanced
      cancer receiving rehabilitation services. DESIGN: A survey of medical
      oncologists' and rehabilitation physicians' self-reported referral attitudes and
      behaviors regarding rehabilitation services for patients with advanced cancer
      defined as the prognosis expected to lead to death in 6-12 months. After a
      prenotification letter, surveys were mailed to a systematically drawn sample. A
      final survey population of 591 medical oncologists and 464 rehabilitation
      physicians was created from prenotification and survey mailings. PARTICIPANTS:
      Practicing physiatrists and oncologists listed in the American Academy of
      Physical Medicine and Rehabilitation and American Society of Clinical Oncology
      membership directories. MAIN OUTCOME MEASUREMENTS: Responses to survey questions
      by physiatrists and oncologists. RESULTS: From 820 surveys mailed, 395 surveys
      were returned, for a total response rate of 46%. When asked about how a terminal
      prognosis of patients with advanced cancer affects rehabilitation referral and
      acceptance, only 8% of medical oncologists said that they would refer a patient
      with advanced cancer to rehabilitation services regardless of estimated
      prognosis, whereas 35% of rehabilitation physicians said that they would accept a
      patient with advanced cancer for rehabilitation services regardless of prognosis.
      Approximately 70% of both medical oncologists and rehabilitation physicians
      thought it to be very important that patients with advanced cancer who are
      referred and accepted into rehabilitation services adequately understand their
      prognosis before beginning a rehabilitation program. However, only 39% of
      rehabilitation physicians, compared with 61% of medical oncologists, believed
      that patients with advanced cancer and in rehabilitation services adequately
      understood their prognosis (P = .004). As surveyed, a do not resuscitate order
      had no effect on a medical oncologist's willingness to refer a patient with
      advanced cancer to rehabilitation services and had minimal effect on a
      rehabilitation physician's willingness to accept a patient with advanced cancer.
      CONCLUSION: Medical oncologists and rehabilitation physicians share many similar
      attitudes with regard to the referral and acceptance of patients with advanced
      cancer for rehabilitation services. However, medical oncologists see prognosis as
      a more significant barrier to rehabilitation services than do rehabilitation
      physicians. Rehabilitation physicians are more likely to believe that the
      patients with advanced cancer for whom they care do not adequately understand
      their prognosis.

PMID- 22373460
TI  - Passive and dynamic shoulder rotation range in uninjured and previously injured
      overhead throwing athletes and the effect of shoulder taping.
AB  - OBJECTIVES: To investigate: (1) the passive and dynamic shoulder internal (IR)
      and external (ER) rotation range of motion (ROM) of 2 groups of asymptomatic
      overhead throwing athletes: one group who had never experienced shoulder symptoms
      and another who had shoulder symptoms >12 months ago, (2) the effect of taping on
      the passive and dynamic IR-ER ROM in both these groups. DESIGN: A within-subject
      repeated measures analysis of variance design to determine the differences in
      passive and dynamic shoulder rotation range and the effect of shoulder taping on
      the rotation range in a group of uninjured and previously injured overhead
      throwing athletes. SETTING: Academic institution sports medicine setting.
      PARTICIPANTS: Twenty-six overhead throwing collegiate athletes: 17 with no
      history of shoulder injury and 9 with previous shoulder injury. METHODS: Passive
      shoulder ROM was measured with a goniometer with the subject in the supine
      position. To measure dynamic ROM, the subjects sat on a chair and threw a
      handball into a net. An 8-camera Vicon Motion Capture system recorded markers
      placed on the upper limb and trunk. Dynamic ROM was calculated with inverse
      kinematics by using OpenSim. MAIN OUTCOME MEASUREMENT: Shoulder IR-ER ROM.
      RESULTS: Dynamic IR-ER ROM was significantly greater than passive IR-ER ROM (P <
      .0001). There was no difference in passive IR-ER ROM between the uninjured and
      previously injured overhead throwing athletes. However, there was a significant
      difference in the total dynamic IR-ER ROM, whereby the overhead throwing athletes
      who had never experienced shoulder symptoms had less IR-ER ROM than the
      previously injured group (173.9 degrees  versus 196.9 degrees , respectively; P =
      .049). Taping the shoulder increased the passive ROM in both groups of subjects
      (P < .001), increased the dynamic IR-ER ROM in the uninjured subjects, but
      decreased the dynamic IR-ER ROM in the previously injured subjects, although this
      was not statistically significant (P = .07). CONCLUSIONS: Passive IR-ER ROM is a
      poor indication of dynamic shoulder function. Athletes who have had a previous
      shoulder injury demonstrate a greater dynamic IR-ER ROM than athletes who have
      never had a shoulder injury. Shoulder taping decreased the dynamic range of the
      previously injured athlete, so that it was nearer the dynamic range of the
      uninjured athlete. Shoulder taping might provide increased protection for the
      injured athlete by decreasing the dynamic IR-ER ROM and by facilitating better
      shoulder and scapular muscle control. Further studies are necessary to
      demonstrate whether this finding is clinically significant.

PMID- 22373461
TI  - The effect of prolonged standing on touch sensitivity threshold of the foot: a
      pilot study.
AB  - OBJECTIVE: To determine the effect of prolonged standing on touch sensitivity of
      the foot. DESIGN: An observational study with replications. SETTING: University
      laboratory. PARTICIPANTS: Ten healthy college students (5 men and 5 women), with
      a mean +/- SD age of 23.5 +/- 4.1 years and body mass of 67.4 +/- 12.6 kg.
      METHODS: Semmes-Weinstein monofilament tests were administered to 12 locations on
      the dorsal and plantar surfaces of the foot before and after 4 hours of standing.
      These locations were formed into several groupings (toes, metatarsal heads,
      midfoot, heel, all plantar sites, all dorsal sites), and paired t-tests were used
      to test for significant changes in sensitivity threshold after standing. MAIN
      OUTCOME MEASUREMENT: The difference between sensitivity thresholds measured
      before and after standing for different locations on the foot. RESULTS: The
      average of all sensitivity thresholds on the plantar surface of the foot
      decreased (indicating increased sensitivity) from 0.56 to 0.36 g (P < .01) after
      4 hours of prolonged standing. This change in threshold equated to a difference
      of 1 Semmes-Weinstein monofilament level. Changes in the sensitivity threshold of
      the dorsal aspect of the foot were not significant. CONCLUSIONS: Analysis of the
      results suggests that the plantar foot has greater sensitivity to touch after
      prolonged standing. These findings may be useful for identifying potential
      unintended bias in clinical touch sensitivity testing. Future research is
      necessary to understand the underlying mechanisms for this sensitivity change and
      to determine the onset and recovery times for sensitivity changes.

PMID- 22373462
TI  - Systematic review of interventions for post-traumatic headache.
AB  - OBJECTIVE: Headache is one of the most common physical symptoms after traumatic
      brain injury (TBI). The specific goals of this review include (1) determination
      of effective interventions for post-traumatic headache (PTHA), (2) development of
      treatment recommendations, (3) identification of gaps in the current medical
      literature regarding PTHA treatment, and (4) suggestions for future directions in
      research to improve outcome for persons with PTHA. DATA SOURCES: Peer-reviewed
      studies in PubMed, CINAHL, PsycINFO, ProQuest, Web of Science, and Google
      Scholar: (1) including adult and child samples with mild, moderate, or severe
      TBI, whiplash, and postconcussion syndrome; (2) with clearly described
      interventions; (3) with headache treatment as a primary or secondary outcome; (4)
      published since 1985; and (5) written in English. STUDY SELECTION: Abstracts from
      812 articles from the above searches were reviewed. All research types that
      studied the treatment of headache after TBI were included, and 64 of the 812
      articles appeared to meet the inclusion criteria. DATA EXTRACTION: The 64
      articles were reviewed in full and data were extracted; 36 met all criteria for
      inclusion. The final 36 articles were rated according to the American Academy of
      Neurology criteria for classifying therapeutic studies. DATA SYNTHESIS: No class
      I studies and only one class II study for the management of PTHA were identified.
      One class I and one class II study for whiplash-associated disorder with headache
      as an outcome were identified. Twelve studies met criteria for class III.
      CONCLUSIONS: No strong evidence from clinical trials is available to direct the
      treatment of PTHA. Some guidelines are offered for PTHA management based on
      primary headache categories and treatments. It is essential that well-designed
      clinical studies be conducted to inform clinicians on the management and
      prevention of PTHA chronicity.

PMID- 22373463
TI  - Understanding change management.

PMID- 22373464
TI  - Persistent hiccups after interventional pain procedures: a case series and
      review.
AB  - Interventional spine procedures are nonsurgical interventions that are commonly
      used to treat acute and chronic pain. These procedures generally are considered
      to be safe, but patients may experience transient and minor complications.
      Hiccups previously have been reported in the pain management setting as a
      complication after lumbar and thoracic epidural steroid injections and an
      intrathecal morphine pump infusion. In this case series of 8 patients, we
      describe hiccups after various interventional procedures, including cervical and
      lumbar epidural steroid injections, facet joint injections, and sacroiliac joint
      injections. A comprehensive literature review of hiccups associated with
      interventional pain procedures is provided, along with the known pathophysiology,
      etiologies, and treatment options for hiccups. The objective of this case series
      presentation and literature review is to highlight the importance of recognizing
      hiccups as a potentially under-reported adverse reaction in the setting of
      various interventional spine procedures.

PMID- 22373465
TI  - Diaphragmatic pacing and protocol with locked-in syndrome.

PMID- 22373466
TI  - Ultrasound versus magnetic resonance imaging in the diagnosis of an acute
      hamstring tear.

PMID- 22373468
TI  - Return to driving and a clinical measure of reaction time.

PMID- 22373469
TI  - Academic departments: the history and future of physical medicine and
      rehabilitation.

PMID- 22373470
TI  - Impact of connecting tuberculosis directly observed therapy short-course with
      smoking cessation on health-related quality of life.
AB  - BACKGROUND: With evolving evidence of association between tuberculosis (TB) and
      tobacco smoking, recommendations for the inclusion of tobacco cessation
      interventions in TB care are becoming increasingly important and more widely
      disseminated. Connecting TB and tobacco cessation interventions has been strongly
      advocated as this may yield better outcomes. However, no study has documented the
      impact of such connection on health-related quality of life (HRQoL). The
      objective of this study was to document the impact of an integrated TB directly
      observed therapy short-course (DOTS) plus smoking cessation intervention (SCI) on
      HRQoL. METHODS: This was a multi-centered non-randomized controlled study
      involving 120 TB patients who were current smokers at the time of TB diagnosis in
      Malaysia. Patients were assigned to either of two groups: the usual TB-DOTS plus
      SCI (SCIDOTS group) or the usual TB-DOTS only (DOTS group). The effect of the
      novel strategy on HRQoL was measured using EQ-5D questionnaire. Two-way repeated
      measure ANOVA was used to examine the effects. RESULTS: When compared,
      participants who received the integrated intervention had a better HRQoL than
      those who received the usual TB care. The SCIDOTS group had a significantly
      greater increase in EQ-5D utility score than the DOTS group during 6 months
      follow-up (mean +/- SD = 0.98 +/- 0.08 vs. 0.91 +/- 0.14, p = 0.006). Similarly,
      the mean scores for EQ-VAS showed a consistently similar trend as the EQ-5D
      indices, with the scores increasing over the course of TB treatment. Furthermore,
      for the EQ-VAS, there were significant main effects for group [F (1, 84) = 4.91,
      p = 0.029, eta2 = 0.06], time [F (2, 168) = 139.50, p = < 0.001, eta2 = 0.62] and
      group x time interaction [F (2, 168) = 13.89, p = < 0.001, eta2 = 0.14].
      CONCLUSIONS: This study supports the evidence that an integrated TB-tobacco
      treatment strategy could potentially improve overall quality of life outcomes
      among TB patients who are smokers.

PMID- 22373472
TI  - Anti-inflammatory new coumarin from the Ammi majus L.
AB  - Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L.
      led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6
      hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated
      from this plant. The structures of the compounds (2 &3) were elucidated by
      spectroscopic data interpretation and showed anti-inflammatory and anti-viral
      activity. GRAPHICAL  An efficient, one-new coumarin (2) was isolated from the
      aerial parts of the A. Majus L. was evaluated for their anti-viral and anti
      inflammatory activities.

PMID- 22373474
TI  - The use of filler DNA for improved transfection and reduced DNA needs in
      transient gene expression with CHO and HEK cells.

PMID- 22373475
TI  - Evaluation of association tests for rare variants using simulated data sets in
      the Genetic Analysis Workshop 17 data.
AB  - We evaluate four association tests for rare variants-the combined multivariate
      and collapsing (CMC) method, two weighted-sum methods, and a variable threshold
      method-by applying them to the simulated data sets of unrelated individuals in
      the Genetic Analysis Workshop 17 (GAW17) data. The family-wise error rate (FWER)
      and average power are used as criteria for evaluation. Our results show that when
      all nonsynonymous SNPs (rare variants and common variants) in a gene are jointly
      analyzed, the CMC method fails to control the FWER; when only rare variants
      (single-nucleotide polymorphisms with minor allele frequency less than 0.05) are
      analyzed, all four methods can control FWER well. All four methods have
      comparable power, which is low for the analysis of the GAW17 data sets. Three of
      the methods (not including the CMC method) involve estimation of p-values using
      permutation procedures that either can be computationally intensive or generate
      inflated FWERs. We adapt a fast permutation procedure into these three methods.
      The results show that using the fast permutation procedure can produce FWERs and
      average powers close to the values obtained from the standard permutation
      procedure on the GAW17 data sets. The standard permutation procedure is
      computationally intensive. 

PMID- 22373477
TI  - Strategies in umbilical cord-derived mesenchymal stem cells expansion: influence
      of oxygen, culture medium and cell separation.

PMID- 22373478
TI  - Use of Micro Bioreactor systems to streamline cell line evaluation and upstream
      process development for monoclonal antibody production.

PMID- 22373479
TI  - Efficient production of recombinant IgG by the GLUT5 co-expression system.

PMID- 22373480
TI  - Efficacy of an inactivated and adjuvanted "ZULVAC((r)) 8 OVIS" vaccine produced
      using single-use bioreactors.

PMID- 22373481
TI  - Comparing nominal and real quality scores on next-generation sequencing genotype
      calls.
AB  - I seek to comprehensively evaluate the quality of the Genetic Analysis Workshop
      17 (GAW17) data set by examining the accuracy of its genotype calls, which were
      based on the pilot3 data of the 1000 Genomes Project. Taking advantage of the
      1000 Genomes Project/HapMap sample intersect, I compared GAW17 genotype calls to
      HapMap III, release 2, genotype calls for an individual. These genotype calls
      should be concordant almost everywhere. Instead I found an astonishingly low
      65.4% concordance. Regarding HapMap as the gold standard, I assume that this is a
      GAW17 data problem and seek to explain this discordance accordingly. I found that
      a large proportion of this discordance occurred outside targeted regions and that
      concordance could be improved to at least 94.6% by simply staying within targeted
      regions, which were sequenced across more samples. Furthermore, I found that in
      certain individuals, high sample counts did little to improve concordance and
      concluded that quality scores for a certain sample's sequence reads were simply
      incorrect.

PMID- 22373482
TI  - Quantification of intracellular nucleotide sugars and formulation of a
      mathematical model for prediction of their metabolism.

PMID- 22373483
TI  - Identity by descent and association analysis of dichotomous traits based on large
      pedigrees.
AB  - The goals of our analysis were to map functional loci, which contribute to the
      case-control status of a trait of interest, using large pedigrees. We used
      logistic regression fitted with the generalized estimation equation to test
      associations between a dichotomous phenotype and all genotyped common and rare
      single-nucleotide polymorphisms. In addition to the association study, we also
      developed and applied a simple and fast identical-by-descent-based test to
      identify loci that were shared among affected individuals more often than
      expected by chance. Among the top significant loci, we assessed the statistical
      power and the false discovery rate of both methods. We also demonstrated that
      family-based studies, compared with the standard population-based association
      studies, have great values and advantages for the discovery of multiple rare
      causal variants.

PMID- 22373484
TI  - Performance of random forests and logic regression methods using mini-exome
      sequence data.
AB  - Machine learning approaches are an attractive option for analyzing large-scale
      data to detect genetic variants that contribute to variation of a quantitative
      trait, without requiring specific distributional assumptions. We evaluate two
      machine learning methods, random forests and logic regression, and compare them
      to standard simple univariate linear regression, using the Genetic Analysis
      Workshop 17 mini-exome data. We also apply these methods after collapsing
      multiple rare variants within genes and within gene pathways. Linear regression
      and the random forest method performed better when rare variants were collapsed
      based on genes or gene pathways than when each variant was analyzed separately.
      Logic regression performed better when rare variants were collapsed based on
      genes rather than on pathways.

PMID- 22373485
TI  - Economic burden of patients with various etiologies of chronic systolic heart
      failure analyzed by resource use and costs.

PMID- 22373487
TI  - Two sides of the Myc-induced DNA damage response: from tumor suppression to tumor
      maintenance.
AB  - Activation of oncogenes is generally associated with the induction of DNA damage
      response (DDR) signaling, which acts as a barrier to tumor progression. In this
      review we will present an overview of the DDR associated with oncogenic
      activation of Myc, with special focus on two opposite and paradoxical aspects of
      this response: (1) the role of the Myc-induced DDR in tumor suppression; (2) its
      role in dampening Myc-induced replication stress, thereby protecting the
      viability of prospective cancer cells. These opposing effects on cancer
      progression are controlled by two different branches of DDR signaling,
      respectively ATM/CHK2 and ATR/CHK1. Indeed, while ATM activity constitutes a
      barrier to malignant transformation, full activation of ATR and CHK1 is essential
      for tumor maintenance, providing important opportunities for therapeutic
      intervention. Thus, the Myc-induced DDR acts as a double-edged sword in tumor
      progression.

PMID- 22373490
TI  - The neuroprotective effects of electrolyzed reduced water and its model water
      containing molecular hydrogen and Pt nanoparticles.

PMID- 22373491
TI  - Regularized regression method for genome-wide association studies.
AB  - We use a novel penalized approach for genome-wide association study that accounts
      for the linkage disequilibrium between adjacent markers. This method uses a
      penalty on the difference of the genetic effect at adjacent single-nucleotide
      polymorphisms and combines it with the minimax concave penalty, which has been
      shown to be superior to the least absolute shrinkage and selection operator
      (LASSO) in terms of estimator bias and selection consistency. Our method is
      implemented using a coordinate descent algorithm. The value of the tuning
      parameters is determined by extended Bayesian information criteria. The leave-one
      out method is used to compute p-values of selected single-nucleotide
      polymorphisms. Its applicability to a simulated data from Genetic Analysis
      Workshop 17 replication one is illustrated. Our method selects three SNPs
      (C13S522, C13S523, and C13S524), whereas the LASSO method selects two SNPs
      (C13S522 and C13S523).

PMID- 22373493
TI  - Abstract withdrawn.

PMID- 22373492
TI  - Smoking and adipose tissue inflammation suppress leptin expression in Japanese
      obese males: potential mechanism of resistance to weight loss among Japanese
      obese smokers.
AB  - BACKGROUND: The effect of smoking on leptin regulation is controversial. Smoking
      may induce low-grade inflammation. Recent series of studies indicated the
      critical role of macrophage migration in the establishment of adipose tissue
      inflammation. In this study, we aimed to see the effects of smoking and
      inflammation on leptin regulation both at cellular and epidemiological levels.
      METHODS: We compared the concentration of inflammatory markers and serum leptin
      levels among Japanese male subjects. Additionally, leptin and intercellular
      adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co
      cultured with or without macrophages in the presence or absence of nicotine
      and/or lipopolysaccharide (LPS). RESULTS: In subjects with BMI below 25 kg/m2,
      both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers
      than in non-smokers. However, leptin concentration did not differ according to
      smoking status. However, in subjects with BMI over 25 kg/m2, smokers exhibited
      significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1
      concentration as compared with non-smokers. Leptin gene expression was markedly
      suppressed in adipocytes co-cultured with macrophages than in adipocyte culture
      alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1
      gene expression was markedly up-regulated in adipocytes co-cultured with
      macrophages when stimulated with LPS. CONCLUSIONS: Adipose tissue inflammation
      appears to down-regulate leptin expression in adipose tissues. Nicotine further
      suppresses leptin expression. Thus, both smoking and inflammation may diminish
      leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers
      might be more resistant to weight loss than non-smokers.

PMID- 22373494
TI  - Testosterone measured in infancy predicts subsequent sex-typed behavior in boys
      and in girls.
AB  - The testes are active during gestation, as well as during early infancy.
      Testosterone elevation during fetal development has been shown to play a role in
      human neurobehavioral sexual differentiation. The role of early postnatal gonadal
      activation in human psychosexual development is largely unknown, however. We
      measured testosterone in 48 full term infants (22 boys, 26 girls) by monthly
      urinary sampling from day 7 postnatal to age 6 months, and related the area under
      the curve (AUC) for testosterone during the first 6 months postnatal to
      subsequent sex-typed behavior, at the age of 14 months, using the Pre-School
      Activities Inventory (PSAI), and playroom observation of toy choices. In boys,
      testosterone AUC correlated significantly with PSAI scores (Spearman's rho =
      0.54, p = 0.04). In addition, play with a train and with a baby doll showed the
      anticipated sex differences, and play with the train correlated significantly and
      positively with testosterone AUC in girls (Spearman's rho = 0.43, p = 0.05),
      while play with the doll correlated significantly and negatively with
      testosterone AUC in boys (Spearman's rho = -0.48, p < 0.03). These results may
      support a role for testosterone during early infancy in human neurobehavioral
      sexual differentiation.

PMID- 22373495
TI  - Rising StARs: behavioral, hormonal, and molecular responses to social challenge
      and opportunity.
AB  - Across taxa, individuals must respond to a dynamic social environment of
      challenges and opportunities on multiple biological levels, including behavior,
      hormone profiles, and gene expression. We investigated the response to a complex
      social environment including both territorial challenges and reproductive
      opportunities in the African cichlid fish Astatotilapia burtoni (Burton's
      mouthbrooder), a species well-known for its phenotypic plasticity. Male A.
      burtoni are either socially dominant or subordinate and can transition between
      the two phenotypes. We used this transition to simultaneously study changes in
      aggression, reproductive behavior, testosterone and estradiol levels, gonadal
      histology, and testes expression of three genes involved in testosterone
      synthesis. We have found that males immediately become aggressive and increase
      testosterone levels when they become dominant in this paradigm of challenge and
      opportunity. Reproductive behavior and estradiol increase slightly later but are
      also up-regulated within 24h. Increases in steroid hormone levels are accompanied
      by an increase in expression of steroidogenic acute regulatory protein (StAR),
      the rate-limiting enzyme during testosterone synthesis, as well as an increase in
      testis maturation as measured by histological organization. Reproductive behavior
      was found to correlate with female gravidity, suggesting that males were able to
      perceive reproductive opportunity. Our study demonstrates the rapid plasticity at
      multiple levels of biological organization that animals can display in response
      to changes in their complex social environment.

PMID- 22373496
TI  - Thyroid hormones and cognitive functioning in healthy, euthyroid women: a
      correlational study.
AB  - Thyroid hormones (THs) play a critical role in differentiation, growth, and
      metabolism of animal and human organ systems, including the brain. Although
      associations between normal levels of THs and cognitive functions in healthy
      elderly individuals have been reported, the findings are inconsistent, possibly
      due to differences in study designs. Because thyroid disease occurs more
      frequently in women, the goal of the present study was to examine the
      relationship between levels of THs and performance on neuropsychological tests in
      122 healthy, euthyroid women whose mean age was 51 years. Higher levels of free
      T3 were positively associated with longer completion times (slower performance)
      on Trail Making Test - Part A (p = 0.006) and Part B (p = 0.032) and on the Tower
      of London test (p = 0.002). Higher levels of thyroglobulin antibodies (TgAb) were
      positively correlated with more errors on the Trail Making Test Part B (p =
      0.000), on the Word Fluency test (p = 0.023), and on the Design Fluency test (p =
      0.045). No significant correlations between TH levels and scores on mood, verbal
      memory, or working memory measures were observed. The findings point to a
      possible link between THs and cognitive processes that are mediated primarily by
      frontal cortex, areas associated with executive function tasks, and suggest that
      elevations in levels of free T3 and TgAB within the normal range may negatively
      influence executive functions.

PMID- 22373497
TI  - Testosterone prevents but not reverses anhedonia in middle-aged males and lacks
      an effect on stress vulnerability in young adults.
AB  - Middle-aged male rats are more vulnerable than young adult ones to develop
      anhedonia when exposed to chronic mild stress (CMS). Clinical studies support the
      idea that in aged subjects the low testosterone (T) levels are related with their
      higher stress vulnerability and that this hormone possesses antidepressant-like
      actions. In this study we evaluated the role of gonadal hormones--mainly T--on
      the depressive-like behavior of middle-aged and young adult male rats submitted
      to CMS. In middle-aged rats we analyzed the effect of T restitution (at the
      levels of young adult animals) given 3 weeks before (experiment 1) or 3 weeks
      after (experiment 2) anhedonia development (indicated by a reduction in sucrose
      solution intake). T restitution before CMS effectively prevented anhedonia but
      failed to reverse it once installed. In young adult rats we studied if
      orchidectomy increased stress vulnerability and found that it failed to modify
      sucrose intake. These results indicate a stress-dependent differential effect of
      T in middle-aged rats an age differential role of gonadal hormones on the
      vulnerability to develop anhedonia. The results suggest that T is a resilience
      factor in middle-aged but not in young adult males.

PMID- 22373498
TI  - Rapid recombinant protein production from pools of transposon-generated CHO
      cells.

PMID- 22373499
TI  - Effect of feedback on delaying deterioration in quality of compressions during 2
      minutes of continuous chest compressions: a randomized manikin study
      investigating performance with and without feedback.
AB  - BACKGROUND: Good quality basic life support (BLS) improves outcome following
      cardiac arrest. As BLS performance deteriorates over time we performed a parallel
      group, superiority study to investigate the effect of feedback on quality of
      chest compression with the hypothesis that feedback delays deterioration of
      quality of compressions. METHODS: Participants attending a national one-day
      conference on cardiac arrest and CPR in Denmark were randomized to perform single
      rescuer BLS with (n = 26) or without verbal and visual feedback (n = 28) on a
      manikin using a ZOLL AED plus. Data were analyzed using Rescuenet Code Review.
      Blinding of participants was not possible, but allocation concealment was
      performed. Primary outcome was the proportion of delivered compressions within
      target depth compared over a 2-minute period within the groups and between the
      groups. Secondary outcome was the proportion of delivered compressions within
      target rate compared over a 2-minute period within the groups and between the
      groups. Performance variables for 30-second intervals were analyzed and compared.
      RESULTS: 24 (92%) and 23 (82%) had CPR experience in the group with and without
      feedback respectively. 14 (54%) were CPR instructors in the feedback group and 18
      (64%) in the group without feedback. Data from 26 and 28 participants were
      analyzed respectively. Although median values for proportion of delivered
      compressions within target depth were higher in the feedback group (0-30 s:
      54.0%; 30-60 s: 88.0%; 60-90 s: 72.6%; 90-120 s: 87.0%), no significant
      difference was found when compared to without feedback (0-30 s: 19.6%; 30-60 s:
      33.1%; 60-90 s: 44.5%; 90-120 s: 32.7%) and no significant deteriorations over
      time were found within the groups. In the feedback group a significant
      improvement was found in the proportion of delivered compressions below target
      depth when the subsequent intervals were compared to the first 30 seconds (0-30
      s: 3.9%; 30-60 s: 0.0%; 60-90 s: 0.0%; 90-120 s: 0.0%). Significant differences
      were not found in secondary outcome and in other performance variables between
      the groups and over time CONCLUSIONS: Quality of CPR was maintained during 2
      minutes of continuous compressions regardless of feedback in a group of trained
      rescuers.

PMID- 22373500
TI  - Study of expansion of porcine bone marrow mesenchymal stem cells on microcarriers
      using various operating conditions.

PMID- 22373501
TI  - Comparison of results from tests of association in unrelated individuals with
      uncollapsed and collapsed sequence variants using tiled regression.
AB  - Tiled regression is an approach designed to determine the set of independent
      genetic variants that contribute to the variation of a quantitative trait in the
      presence of many highly correlated variants. In this study, we evaluate the
      statistical properties of the tiled regression method using the Genetic Analysis
      Workshop 17 data in unrelated individuals for traits Q1, Q2, and Q4. To increase
      the power to detect rare variants, we use two methods to collapse rare variants
      and compare the results with those from the uncollapsed data. In addition, we
      compare the tiled regression method to traditional tests of association with and
      without collapsed rare variants. The results show that collapsing rare variants
      generally improves the power to detect associations regardless of method,
      although only variants with the largest allelic effects could be detected.
      However, for traditional simple linear regression, the average estimated type I
      error is dependent on the trait and varies by about three orders of magnitude.
      The estimated type I error rate is stable for tiled regression across traits.

PMID- 22373502
TI  - Genome-wide association analysis of GAW17 data using an empirical Bayes variable
      selection.
AB  - Next-generation sequencing technologies enable us to explore rare functional
      variants. However, most current statistical techniques are too underpowered to
      capture signals of rare variants in genome-wide association studies. We propose a
      supervised coalescing of single-nucleotide polymorphisms to obtain gene-based
      markers that can stably reveal possible genetic effects related to rare alleles.
      We use a newly developed empirical Bayes variable selection algorithm to identify
      associations between studied traits and genetic markers. Using our novel method,
      we analyzed the three continuous phenotypes in the GAW17 data set across 200
      replicates, with intriguing results.

PMID- 22373503
TI  - Cell line selection using the Duetz Microflask system.

PMID- 22373504
TI  - Do rare variant genotypes predict common variant genotypes?
AB  - The synthetic association hypothesis proposes that common genetic variants
      detectable in genome-wide association studies may reflect the net phenotypic
      effect of multiple rare polymorphisms distributed broadly within the focal gene
      rather than, as often assumed, the effect of common functional variants in high
      linkage disequilibrium with the focal marker. In a recent study, Dickson and
      colleagues demonstrated synthetic association in simulations and in two well
      characterized, highly polymorphic human disease genes. The converse of this
      hypothesis is that rare variant genotypes must be correlated with common variant
      genotypes often enough to make the phenomenon of synthetic association possible.
      Here we used the exome genotype data provided for Genetic Analysis Workshop 17 to
      ask how often, how well, and under what conditions rare variant genotypes predict
      the genotypes of common variants within the same gene. We found nominal evidence
      of correlation between rare and common variants in 21-30% of cases examined for
      unrelated individuals; this rate increased to 38-44% for related individuals,
      underscoring the segregation that underlies synthetic association.

PMID- 22373505
TI  - Comparison of genetic association strategies in the presence of rare alleles.
AB  - In the quest for the missing heritability of most complex diseases, rare variants
      have received increased attention. Advances in large-scale sequencing have led to
      a shift from the common disease/common variant hypothesis to the common
      disease/rare variant hypothesis or have at least reopened the debate about the
      relevance and importance of rare variants for gene discoveries. The investigation
      of modeling and testing approaches to identify significant disease/rare variant
      associations is in full motion. New methods to better deal with parameter
      estimation instabilities, convergence problems, or multiple testing corrections
      in the presence of rare variants or effect modifiers of rare variants are in
      their infancy. Using a recently developed semiparametric strategy to detect
      causal variants, we investigate the performance of the model-based multifactor
      dimensionality reduction (MB-MDR) technique in terms of power and family-wise
      error rate (FWER) control in the presence of rare variants, using population
      based and family-based data (FAM-MDR). We compare family-based results obtained
      from MB-MDR analyses to screening findings from a quantitative trait Pedigree
      based association test (PBAT). Population-based data were further examined using
      penalized regression models. We restrict attention to all available single
      nucleotide polymorphisms on chromosome 4 and consider Q1 as the outcome of
      interest. The considered family-based methods identified marker C4S4935 in the
      VEGFC gene with estimated power not exceeding 0.35 (FAM-MDR), when FWER was kept
      under control. The considered population-based methods gave rise to highly
      inflated FWERs (up to 90% for PBAT screening).

PMID- 22373506
TI  - Chemical composition and antibacterial activity of the essential oils from
      Launaea resedifolia L.
AB  - BACKGROUND: Several species of the genus Launaea are used in folk medicine such
      as in bitter stomachic, skin diseases, and reported to have antitumor,
      insecticide, and cytotoxic activities. The antimicrobial activities of coumarin
      constituents and the neuropharmacological properties have been investigated as
      well. In this study, the chemical composition of essential oils from Launaea
      resedifolia L. has been identified using the ordinary GC-MS technique to reveal
      the presence of 19 compounds dominated by dioctyl phthalate. Moreover, the
      antibacterial activity of the crude oil has been carried out using disk diffusion
      method against seven bacteria strains. RESULTS: Nineteen compounds of essential
      oil of L. resedifolia L. were identified, representing 86.68% of the total oil.
      The compounds were identified by spectral comparison to be mainly esters,
      alcohols, ketones, and terpenes. The principal constituents are dioctyl phthalate
      (39.84%), Decanoic acid, decyl ester (12.09%), 11-Octadecenal (11.24%), and
      Eucalyptol (07.31%), while others were present in relatively small amounts. As
      far as antibacterial essays are concerned, it was found that the oils are active
      against most of the tested bacterial strains. CONCLUSION: A major constituent in
      visible parts was Dioctyl phthalate (39.84%) and the yield of essential oils was
      0.9%. These extracts reveal in vitro antibacterial activity on the studied
      bacterial, confirmed by the inhibition zone diameter ranging from 11 to 37 mm and
      a MIC value between 0.09 and 0.69 depending on the microorganism being tested.

PMID- 22373507
TI  - Engineering CHO cell metabolism for growth in galactose.

PMID- 22373510
TI  - A strategy to obtain recombinant cell lines with high expression levels.
      Lentiviral vector-mediated transgenesis.

PMID- 22373512
TI  - Amino acid sequence coevolution in the insect bursicon ligand-receptor system.
AB  - The pattern of amino acid residue replacement in the components of the bursicon
      signaling system (involving the BURSalpha/BURSbeta heterodimer and its receptor
      BURSrec) was reconstructed across a phylogeny of 17 insect species, in order to
      test for the co-occurrence of replacements at sets of individual sites. Sets of
      three or more branches with perfectly concordant changes occurred to a greater
      extent than expected by chance, given the observed level of amino acid change.
      The latter sites (SPC sites) were found to have distinctive characteristics: (1)
      the mean number of changes was significantly lower at SPC sites than that at
      other sites with multiple changes; (2) SPC sites had a significantly greater
      tendency toward parallel amino acid changes than other sites with multiple
      changes, but no greater tendency toward convergent changes; and (3) parallel
      changes tended to involve relatively similar amino acids, as indicated by
      relatively low mean chemical distances. The results implicated functional
      constraint, permitting only a limited subset of amino acids in a given site, as a
      major factor in causing both parallel amino acid replacement and coordinated
      amino acid changes in different sites of the same protein and of interacting
      proteins in this system.

PMID- 22373513
TI  - Future development of global regulations of Chinese herbal products.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: GP-TCM is the first EU-funded Coordination Action
      consortium dedicated to traditional Chinese medicine (TCM) research. One of the
      key deliverables of the Work Package 7 in GP-TCM was to investigate information
      of the existing requirements for registration of TCM products listed by global
      regulatory bodies. The paper aims to collate data and draw comparison of these
      regulations. Case studies are also presented to illustrate the problems involved
      in registering TCM products in different regions worldwide. MATERIALS AND
      METHODS: A collaborative network task force was established during the early
      stage of the GP-TCM project and operated through exchanges, teleconferences and
      focused discussions at annual meetings. The task force involved coordinators,
      academics who are actively involved with R&D of Chinese herbal medicines, experts
      on monographic standards of Chinese materia medica, representatives from
      regulatory agencies, experts from industries in marketing Chinese
      medicines/herbal medicines and natural products. The co-ordinators took turns to
      chair teleconferences, led discussions on specific issues at AGM discussion
      sessions, at joint workshops with other work-packages such as WP1 (quality
      issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively
      the authors were responsible for collating discussion outcomes and updating
      written information. RESULTS: A global overview of regulations on herbal
      registration has been compiled during the three years of the consortium. The
      regulatory requirements for registration of herbal products in the EU and China
      were compared, and this is extended to other regions/countries: Africa,
      Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United
      States. A wide variation of the regulations for the categories of herbal products
      exists: food (functional food, novel foods, dietary food for special medical
      purpose, foods for particular nutritional use, food supplement); cosmetic,
      traditional herbal medicine products; herbal medicines for human use and
      veterinary use. CONCLUSION: The regulatory issues for registration of herbal
      products are complicated among the countries and regions worldwide. The
      information summarised in the text is for reference only. Some regulations which
      are presented in this review are still in legislation process and may change in
      due course. Before taking any regulatory action, readers are advised to consult
      current official legislation and guidance and/or to seek appropriate professional
      advice. The lessons learnt from global regulation of TCM will provide valuable
      insights for regulation of other traditional medicine such as Ayurveda and Unani
      medicine, as well as other forms of indigenous medicine. The WHO is well placed
      to co-ordinate a consultation process with the aim of putting forward suggestions
      for harmonisation to key regulatory agencies.

PMID- 22373515
TI  - Innovative animal component-free surface for the cultivation of human embryonic
      stem cells.

PMID- 22373514
TI  - Point specificity in acupuncture.
AB  - The existence of point specificity in acupuncture is controversial, because many
      acupuncture studies using this principle to select control points have found that
      sham acupoints have similar effects to those of verum acupoints. Furthermore, the
      results of pain-related studies based on visual analogue scales have not
      supported the concept of point specificity. In contrast, hemodynamic, functional
      magnetic resonance imaging and neurophysiological studies evaluating the
      responses to stimulation of multiple points on the body surface have shown that
      point-specific actions are present. This review article focuses on clinical and
      laboratory studies supporting the existence of point specificity in acupuncture
      and also addresses studies that do not support this concept. Further research is
      needed to elucidate the point-specific actions of acupuncture.

PMID- 22373516
TI  - Identifying variants that contribute to linkage for dichotomous and quantitative
      traits in extended pedigrees.
AB  - Compared to genome-wide association analysis, linkage analysis is less influenced
      by allelic heterogeneity. The use of linkage information in large families should
      provide a great opportunity to identify less frequent variants. We perform a
      linkage scan for both dichotomous and quantitative traits in eight extended
      families. For the dichotomous trait, we identified one linkage region on
      chromosome 4q. For quantitative traits, we identified two regions on chromosomes
      4q and 6p for Q1 and one region on chromosome 6q for Q2. To identify variants
      that contribute to these linkage signals, we performed standard association
      analysis in genomic regions of interest. We also screened less frequent variants
      in the linkage region based on the risk ratio and phenotypic distribution among
      carriers. Two rare variants at VEGFC and one common variant on chromosome 4q
      conferred the greatest risk for the dichotomous trait. We identified two rare
      variants on chromosomes 4q (VEGFC) and 6p (VEGFA) that explain 12.4% of the total
      phenotypic variance of trait Q1. We also identified four variants (including one
      at VNN3) on chromosome 6q that are able to drop the linkage LOD from 3.7 to 1.0.
      These results suggest that the use of classical linkage and association methods
      in large families can provide a useful approach to identifying variants that are
      responsible for diseases and complex traits in families.

PMID- 22373517
TI  - Digging into the extremes: a useful approach for the analysis of rare variants
      with continuous traits?
AB  - The common disease/rare variant hypothesis predicts that rare variants with large
      effects will have a strong impact on corresponding phenotypes. Therefore it is
      assumed that rare functional variants are enriched in the extremes of the
      phenotype distribution. In this analysis of the Genetic Analysis Workshop 17 data
      set, my aim is to detect genes with rare variants that are associated with
      quantitative traits using two general approaches: analyzing the association with
      the complete distribution of values by means of linear regression and using
      statistical tests based on the tails of the distribution (bottom 10% of values
      versus top 10%). Three methods are used for this extreme phenotype approach:
      Fisher's exact test, weighted-sum method, and beta method. Rare variants were
      collapsed on the gene level. Linear regression including all values provided the
      highest power to detect rare variants. Of the three methods used in the extreme
      phenotype approach, the beta method performed best. Furthermore, the sample size
      was enriched in this approach by adding additional samples with extreme phenotype
      values. Doubling the sample size using this approach, which corresponds to only
      40% of sample size of the original continuous trait, yielded a comparable or even
      higher power than linear regression. If samples are selected primarily for
      sequencing, enriching the analysis by gathering a greater proportion of
      individuals with extreme values in the phenotype of interest rather than in the
      general population leads to a higher power to detect rare variants compared to
      analyzing a population-based sample with equivalent sample size.

PMID- 22373518
TI  - New insights into old methods for identifying causal rare variants.
AB  - The advance of high-throughput next-generation sequencing technology makes
      possible the analysis of rare variants. However, the investigation of rare
      variants in unrelated-individuals data sets faces the challenge of low power, and
      most methods circumvent the difficulty by using various collapsing procedures
      based on genes, pathways, or gene clusters. We suggest a new way to identify
      causal rare variants using the F-statistic and sliced inverse regression. The
      procedure is tested on the data set provided by the Genetic Analysis Workshop 17
      (GAW17). After preliminary data reduction, we ranked markers according to their F
      statistic values. Top-ranked markers were then subjected to sliced inverse
      regression, and those with higher absolute coefficients in the most significant
      sliced inverse regression direction were selected. The procedure yields good
      false discovery rates for the GAW17 data and thus is a promising method for
      future study on rare variants.

PMID- 22373519
TI  - Intraluminal ultrasonic probe for volumetric monitoring of liquid
      gastroesophageal reflux.
AB  - Methods for volumetric monitoring of liquid gastroesophageal reflux (GER) are
      still lacking. The aim of this study was to develop an automated intraluminal
      measurement technique which allows ambulatory volumetric quantification of liquid
      GER utilizing a minimum-cost intraluminal ultrasonic probe. This probe consists
      of two 2 MHz ultrasonic crystals longitudinally assembled along a multi-channel
      intraluminal impedance (MII) catheter. The proposed probe was initially tested
      with tubular phantoms of different diameters. Measurements of the cross-sectional
      areas of the phantoms showed high correlation with the actual areas (R(2) =
      0.99). Subsequently, two in-vivo human tests were performed. For each human test
      the catheter assembly was inserted transnasally and the ultrasonic probe was
      placed in the area of the lower esophageal sphincter. Multiple liquid swallows of
      different volumes were invoked using electrolyte drinks. Sectional luminal volume
      (SLV) in the esophagus between the two ultrasonic crystals was obtained. Results
      of the swallows demonstrated that measured SLVs correlated with the actual
      swallowed liquid volume. The ultrasonic probe was combined with a MII catheter to
      discriminate between antegrade and retrograde bolus transit. Increases of SLVs
      during liquid GER episodes could be utilized to evaluate GER volume in the
      vicinity of the ultrasonic probe.

PMID- 22373520
TI  - An ontology-based exploration of the concepts and relationships in the activities
      and participation component of the international classification of functioning,
      disability and health.
AB  - BACKGROUND: The International Classification of Functioning, Disability and
      Health (ICF) is a classification of health and health-related issues, aimed at
      describing and measuring health and disability at both individual and population
      levels. Here we discuss a preliminary qualitative and quantitative analysis of
      the relationships used in the Activities and Participation component of ICF, and
      a preliminary mapping to SUMO (Suggested Upper Merged Ontology) concepts. The aim
      of the analysis is to identify potential logical problems within this component
      of ICF, and to understand whether activities and participation might be defined
      more formally than in the current version of ICF. RESULTS: In the relationship
      analysis, we used four predicates among those available in SUMO for processes
      (Patient, Instrument, Agent, and subProcess). While at the top level subsumption
      was used in most cases (90%), at the lower levels the percentage of other
      relationships rose to 41%. Chapters were heterogeneous in the relationships used
      and some of the leaves of the tree seemed to represent properties or parts of the
      parent concept rather than subclasses. Mapping of ICF to SUMO proved partially
      feasible, with the activity concepts being mapped mostly (but not totally) under
      the IntentionalProcess concept in SUMO. On the other hand, the participation
      concept has not been mapped to any upper level concept. CONCLUSIONS: Our analysis
      of the relationships within ICF revealed issues related to confusion between
      classes and their properties, incorrect classifications, and overemphasis on
      subsumption, confirming what already observed by other researchers. However, it
      also suggested some properties for Activities that could be included in a more
      formal model: number of agents involved, the instrument used to carry out the
      activity, the object of the activity, complexity of the task, and an enumeration
      of relevant subtasks.

PMID- 22373521
TI  - Capability of common SNPs to tag rare variants.
AB  - Genome-wide association studies are based on the linkage disequilibrium pattern
      between common tagging single-nucleotide polymorphisms (SNPs) (i.e., SNPs having
      only common alleles) and true causal variants, and association studies with rare
      SNP alleles aim to detect rare causal variants. To better understand and explain
      the findings from both types of studies and to provide clues to improve the power
      of an association study with only common SNPs genotyped, we study the correlation
      between common SNPs and the presence of rare alleles within a region in the
      genome and look at the capability of common SNPs in strong linkage disequilibrium
      with each other to capture single rare alleles. Our results indicate that common
      SNPs can, to some extent, tag the presence of rare alleles and that including
      SNPs in strong linkage disequilibrium with each other among the tagging SNPs
      helps to detect rare alleles.

PMID- 22373522
TI  - Evaluation of an online biomass probe to monitor cell growth and cell death.

PMID- 22373523
TI  - Comparative study of statistical methods for detecting association with rare
      variants in exome-resequencing data.
AB  - Genome-wide association studies for complex traits are based on the common
      disease/common variant (CDCV) and common disease/rare variant (CDRV) assumptions.
      Under the CDCV hypothesis, classical genome-wide association studies using single
      marker tests are powerful in detecting common susceptibility variants, but under
      the CDRV hypothesis they are not as powerful. Several methods have been recently
      proposed to detect association with multiple rare variants collectively in a
      functional unit such as a gene. In this paper, we compare the relative
      performance of several of these methods on the Genetic Analysis Workshop 17 data.
      We evaluate these methods using the unrelated individual and family data sets.
      Association was tested using 200 replicates for the quantitative trait Q1.
      Although in these data the power to detect association is often low, our results
      show that collapsing methods are promising tools. However, we faced the challenge
      of assessing the proper type I error to validate our power comparisons. We
      observed that the type I error rate was not well controlled; however, we did not
      find a general trend specific to each method. Each method can be conservative or
      nonconservative depending on the studied gene. Our results also suggest that
      collapsing and the single-locus association approaches may not be affected to the
      same extent by population stratification. This deserves further investigation.

PMID- 22373524
TI  - Synthesis and anti-HSV-1 evaluation of new 3H-benzo[b]pyrazolo[3,4-h]-1,6
      naphthyridines and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines.
AB  - BACKGROUND: Herpes simplex virus type-1 (HSV-1) is the primary cause of facial
      lesions (mouth, lips, and eyes) in humans. The widespread use of acyclovir and
      nucleoside analogues has led to emergence of HSV strains that are resistant to
      these drugs. Recently, non-nucleoside anti-HSV compounds have received
      considerable attention. 1,6-Naphthyridines are a class of heterocyclic compounds
      that exhibit a broad spectrum of biological activities such as inhibitor of HIV-1
      integrase, HCMV, FGF receptor-1 tyrosine kinase, and the enzyme
      acetylcholinesterase. We previously reported the synthesis, SAR studies, and
      evaluation anti-HSV-1 activity of 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines.
      In the course of our search for new 1,6-naphthyridines derivatives with potential
      activity against HSV-1, we have synthesized and evaluated new 3H
      benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines (1a-k) and 3H-pyrido[2,3
      b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c). RESULTS: A known synthetic approach
      was used for preparing new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines (1a-k)
      and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c), starting from
      ethyl 4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (7). All
      compounds were identified by FTIR, 1H NMR, and mass spectrometry. The antiviral
      effect on HSV-1 virus replication was determined. CONCLUSIONS: The compounds 1d,
      1f, 1g, and 1h exhibited the highest anti-HSV-1 activity. In general, 3H
      benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines were more effective inhibitors than
      their corresponding 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines. The
      compound 1h reduced the virus yield in 91% at 50 MUM and exhibited a low
      cytotoxicity (CC50 600 MUM).

PMID- 22373525
TI  - RPA and POT1: friends or foes at telomeres?
AB  - Telomere maintenance in cycling cells relies on both DNA replication and capping
      by the protein complex shelterin. Two single-stranded DNA (ssDNA)-binding
      proteins, replication protein A (RPA) and protection of telomere 1 (POT1) play
      critical roles in DNA replication and telomere capping, respectively. While RPA
      binds to ssDNA in a non-sequence-specific manner, POT1 specifically recognizes
      singlestranded TTAGGG telomeric repeats. Loss of POT1 leads to aberrant
      accumulation of RPA at telomeres and activation of the ataxia telangiectasia and
      Rad3-related kinase (ATR)-mediated checkpoint response, suggesting that POT1
      antagonizes RPA binding to telomeric ssDNA. The requirement for both POT1 and RPA
      in telomere maintenance and the antagonism between the two proteins raises the
      important question of how they function in concert on telomeric ssDNA. Two
      interesting models were proposed by recent studies to explain the regulation of
      POT1 and RPA at telomeres. Here, we discuss how these models help unravel the
      coordination, and also the antagonism, between POT1 and RPA during the cell
      cycle.

PMID- 22373526
TI  - New insights into replication origin characteristics in metazoans.
AB  - We recently reported the identification and characterization of DNA replication
      origins (Oris) in metazoan cell lines. Here, we describe additional bioinformatic
      analyses showing that the previously identified GC-rich sequence elements form
      origin G-rich repeated elements (OGREs) that are present in 67% to 90% of the DNA
      replication origins from Drosophila to human cells, respectively. Our analyses
      also show that initiation of DNA synthesis takes place precisely at 160 bp
      (Drosophila) and 280 bp (mouse) from the OGRE. We also found that in most CpG
      islands, an OGRE is positioned in opposite orientation on each of the two DNA
      strands and detected two sites of initiation of DNA synthesis upstream or
      downstream of each OGRE. Conversely, Oris not associated with CpG islands have a
      single initiation site. OGRE density along chromosomes correlated with previously
      published replication timing data. Ori sequences centered on the OGRE are also
      predicted to have high intrinsic nucleosome occupancy. Finally, OGREs predict G
      quadruplex structures at Oris that might be structural elements controlling the
      choice or activation of replication origins.

PMID- 22373527
TI  - NER and DDR: classical music with new instruments.
AB  - Genomic insults by endogenous or exogenous sources activate the DNA damage
      response (DDR). After the recognition of damaged DNA by specific factors, repair
      mechanisms process the lesions, and a surveillance mechanism, known as DNA damage
      checkpoint, is triggered by single-stranded (ss) DNA covered by RPA. UV light
      induces DNA lesions, mainly 6,4 photoproducts (6-4PP) and cyclobutane pyrimidine
      dimers (CPD), which are removed by nucleotide excision repair (NER). Recent
      reports shed light onto the mechanism connecting NER and DDR after UV
      irradiation. How does UV-induced DNA damage activate checkpoint kinases? How is
      ssDNA generated at UV lesions? In yeast, UV lesions persisting during S phase
      represent a block for the advancing of replication forks, which temporarily stop
      and then reinitiate downstream of the damage, leaving a ssDNA region containing
      the lesion. Nonreplicating yeast and human cells with defects in NER are not able
      to properly activate the checkpoint cascade, indicating that processing of UV
      lesions is a prerequisite for checkpoint activation. This pathway also requires
      the function of exonuclease 1, which acts on NER intermediates generating long
      tracts of ssDNA. Here, we review the connections between NER processing of UV
      induced lesions and checkpoint activation, discussing the role of recently
      identified players in this mechanism.

PMID- 22373528
TI  - The emerging role of the TGFbeta tumor suppressor pathway in pancreatic cancer.
AB  - Pancreatic adenocarcinoma is one of the most aggressive human cancers. It
      displays many different chromosomal abnormalities and mutations. To design new
      therapeutic strategies, it is important to identify the signaling pathways and
      gene networks within this apparent complexity that are predominantly altered. The
      TGFbeta signaling pathway and associated transcription network emerges as a
      central actor of pancreatic oncogenesis. Its tumor suppressor function in this
      tissue can be affected by several alterations.

PMID- 22373530
TI  - Avian cell line - Technology for large scale vaccine production.

PMID- 22373529
TI  - Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and
      differentiation of adult pancreatic progenitors and mediates islet regeneration.
AB  - The molecular mechanism of beta-cell regeneration remains poorly understood.
      Cyclin D2/CDK4 expresses in normal beta cells and maintains adult beta-cell
      growth. We hypothesized that gene therapy with cyclin D2/CDK4/GLP-1 plasmids
      targeted to the pancreas of STZ-treated rats by ultrasound-targeted microbubble
      destruction (UTMD) would force cell cycle re-entry of residual G(0)-phase islet
      cells into G(1)/S phase to regenerate beta cells. A single UTMD treatment induced
      beta-cell regeneration with reversal of diabetes for 6 mo without evidence of
      toxicity. We observed that this beta-cell regeneration was not mediated by self
      replication of pre-existing beta cells. Instead, cyclin D2/CDK4/GLP-1 initiated
      robust proliferation of adult pancreatic progenitor cells that exist within
      islets and terminally differentiate to mature islets with beta cells and alpha
      cells.

PMID- 22373531
TI  - 3D-MRI of the ankle with optimized 3D-SPACE.
AB  - PURPOSE: To assess the use of 3-dimensional (3D) MR imaging of the ankle with the
      3D-turbo-spin-echo-sequence 3D-"Sampling Perfection with Application optimized
      Contrast using different flip angle Evolutions" (SPACE), as compared with 2
      dimensional-turbo-spin-echo-sequence. MATERIAL AND METHODS: After internal review
      board's approval and informed consent, 15 healthy volunteers and 45 consecutive
      patients were examined at 3 T with isotropic fat-saturated moderately T2-weighted
      3D-SPACE (voxel size: 0.6(3) mm(3)/acquisition time: 6:43 minutes) featuring
      radial k-space reordering for optimized contrast. Signal- and contrast-to-noise
      ratios (SNR; CNR, respectively) were calculated with the subtraction method.
      Using free 3D reconstructions, 2 radiologists independently assessed depiction of
      cartilage, ligaments, and tendons, as well as detection and grading of
      abnormalities of these structures (5-point Likert scale) compared with
      conventional 2-dimensional-TSE-sequences (voxel size: 0.4 * 0.4 * 3 mm(3)/total
      acquisition time: 11 minutes). Statistical analysis was performed with Wilcoxon
      signed rank tests, 95% and 99% confidence intervals and weighted kappa
      coefficients. RESULTS: SNR and CNR of fluid/cartilage were significantly higher
      for 3D-SPACE (P < 0.05). The isotropic voxel size facilitated improved depiction
      of the medial and lateral ankle ligaments with significant differences for the
      calcaneofibular ligament and the anteromedial ligament complex (P < 0.05). In the
      patient cohort, cartilage and spring ligaments were also significantly better
      depicted (P < 0.05). However, there were no significant differences in the number
      or in the diagnostic confidence of detected cartilage, ligament, or tendon
      abnormalities. Interreader correlation was good (kappa = 0.69-0.71) for both
      sequences. The correlation between the 2 sequences was excellent (kappa = 0.84
      0.85). CONCLUSION: 3D-SPACE allows 3D acquisition and assessment of the ankle and
      facilitates depiction of the complex ankle anatomy at sufficient SNR and CNR.

PMID- 22373532
TI  - Quantification of perfusion and permeability in multiple sclerosis: dynamic
      contrast-enhanced MRI in 3D at 3T.
AB  - BACKGROUND AND PURPOSE: The quantification of cerebral blood flow (CBF), cerebral
      blood volume (CBV), and blood-brain barrier permeability in scattered lesions in
      the brain is a methodological challenge. We aimed to investigate the feasibility
      of a 3D T1-weighted dynamic contrast-enhanced (DCE) MRI acquisition in
      combination with a 2-compartment modeling approach for the quantification of CBF,
      CBV and permeability surface area product (PS) in lesions, and normal-appearing
      white matter (NAWM) in patients with multiple sclerosis (MS). MATERIAL AND
      METHODS: In all, 19 MS patients (mean age 35 years, 12 female) underwent DCE-MRI
      with a 3D T1-weighted spoiled gradient-echo sequence on a 3T MRI scanner. A total
      of 44 slices (thickness 3 mm) with an in-plane resolution of 1.7 * 1.7 mm(2)
      (matrix size 128 * 104), providing coverage of the whole brain, were acquired
      every 2.1 seconds over a total measurement time of 420 s. Data postprocessing was
      performed using a set of 2-compartment models with automated model selection;
      CBF, CBV, and PS as a measure of blood-brain barrier leakage were determined in
      contrast-enhancing (CE) and nonenhancing lesions as well as in NAWM. RESULTS:
      Perfusion quantification produced reasonable values in lesions as well as in
      NAWM. In CE lesions, CBF (22.9 (22.7) vs. 15.8 (6.7) mL/100 mL/min), CBV (1.18
      (0.48) vs. 0.76 (0.19) mL/100 mL), and PS (0.98 (0.46) vs. 0.04 (0.03) mL/100
      mL/min) were significantly (P < 0.001) higher than in NAWM. In nonenhancing
      lesions, a weakly (P < 0.05) significantly increased CBV of 1.00 (0.35) mL/100
      mL, compared with NAWM, was observed. CONCLUSION: Our study demonstrates the
      feasibility of 3D T1-weighted DCE-MRI for the quantitative assessment of CBF,
      CBV, and PS in NAWM as well as in multiple MS lesions scattered throughout the
      brain, even without previous knowledge of their location. Quantification on the
      region level produced reasonable values both in lesions and in NAWM, but
      parameter maps would benefit from an increase in contrast-to-noise ratio. The
      increased values of CBF, CBV, and PS in CE lesions may reflect inflammatory
      activity, the heterogeneity of parameter estimates suggests a potential for
      lesion characterization. NAWM appears hypoperfused, this is in accordance with
      previous studies, but requires validation with a control group.

PMID- 22373534
TI  - Comparison of retrospectively self-gated and prospectively triggered FLASH
      sequences for cine imaging of the aorta in mice at 9.4 Tesla.
AB  - OBJECTIVE: A critical problem in cardiovascular MRI in small rodents is adjusting
      the sequence acquisition to the high heart and respiratory rates. The aim of this
      study was to compare a retrospectively self-gated fast low angle shot navigator
      (RSG-FLASH) sequence with a conventional prospectively triggered (PT-FLASH)
      sequence for cine imaging of the ascending aorta in mice at 9.4 T. MATERIAL AND
      METHODS: Ten C57/BL6 mice were examined with a horizontal bore 9.4 Tesla MRI
      animal scanner using a dedicated 2 * 2 phased-array surface coil. We acquired a
      RSG-FLASH sequence (RSG-FLASH sequences (repetition time (TR) / echo time (TE) =
      6.5/2.5 ms, flip angle (FA) = 10 degrees, field of view (FOV) = 2 * 2 cm, matrix
      = 384 * 384, slice thickness = 1 mm, 25 movie frames) perpendicular to the
      ascending aorta using the IntraGate technique. At the same position, we performed
      a PT-FLASH sequence (TR/TE = 6.5/2.1 ms, FA = 10 degrees, FOV = 2 * 2 cm, matrix
      = 384 * 384, slice thickness = 1 mm) in which the maximum number of movie frames
      had to be adjusted to the interval between two R-peaks (RR interval) of the
      electrocardiogram (ECG) with: number of frames = RR interval / TR." Cross
      sectional vessel areas at end-systole (AES) and end-diastole (AED) were measured
      to determine the aortic strain (DeltaA = (AES-AED)/AED). Two blinded readers
      rated the sequences for presence of flow and trigger artifacts and their
      influence on the depiction of the blood/vessel-wall interface. Irregularities in
      displaying the cardiac cycle and the overall suitability of the sequence for
      aortic strain evaluation were assessed using a 5-level ordinal scale. Statistical
      differences were analyzed using Student t test and Wilcoxon signed rank test (P <
      0.05). Intra- and interobserver variability was evaluated using Bland-Altman
      analyses. RESULTS: No significant differences were noted between techniques
      regarding the measured vessel areas (AED: P = 0.07, AES: P = 0.34), DeltaA: P =
      0.1). Similarly, there were no significant differences in heart (P = 0.06) and
      respiratory (P = 0.24) rates. The acquisition time for RSG-FLASH sequence was
      significantly shorter (P = 0.04). Significantly fewer flow and trigger artifacts
      were noted by both readers with the RSG-FLASH sequence. Likewise, both readers
      considered the RSG-FLASH sequence to be superior for depiction of the
      blood/vessel-wall interface. The RSG-FLASH sequence was also rated superior
      regarding irregularities in displaying the cardiac cycle and in terms of overall
      suitability for evaluation of AED, AES, and aortic strain (P < 0.05 each).
      CONCLUSION: RSG-FLASH is preferable for cine imaging of the aorta. It provides
      the same quantitative data as PT-FLASH cine imaging but is less prone to flow and
      trigger artifacts. RSG-FLASH permits more homogeneous depiction of the cardiac
      cycle and is faster than the PT-FLASH sequence. PT-FLASH is more prone to
      misregistration of the respiratory cycle or the ECG by the external monitoring
      device used for acquisition. This effect may be even more pronounced in animals
      with disease models that are less stable in terms of heart and respiration rate
      during anesthesia.

PMID- 22373533
TI  - In vitro and in vivo high-intensity focused ultrasound thrombolysis.
AB  - OBJECTIVES: To characterize the ability of high-intensity focused ultrasound to
      achieve thrombolysis in vitro and investigate the feasibility of this approach as
      a means of restoring blood flow in thrombus-occluded arteries in vivo. MATERIALS
      AND METHODS: All experiments were approved by the Institutional Animal Care
      Committee. Thrombolysis was performed with a 1.51-MHz focused ultrasound
      transducer with pulse lengths of 0.1 to 10 milliseconds and acoustic powers up to
      300 W. In vitro experiments were performed with blood clots formed from rabbit
      arterial blood and situated in 2-mm diameter tubing. Both single location and
      flow bypass recanalization experiments were conducted. In vitro clot erosion was
      assessed with 30-MHz ultrasound, with debris size measured with filters and a
      Coulter counter. In vivo clots were initiated in the femoral arteries of rabbits
      (n = 26). Cavitation signals from bubbles formed during exposure were monitored.
      In vivo flow restoration was assessed with 23-MHz Doppler ultrasound. RESULTS: At
      a single location, in vitro clot erosion volumes increased with exposure power
      and pulse length, with debris size reducing with increasing pulse length. Flow
      bypass experiments achieved 99.2% clot erosion with 1.1% of debris above 0.5 mm
      in size. In vivo, 10 milliseconds pulses were associated with bleeding, but at 1
      millisecond, it was feasible to achieve partial flow restoration in 6 of the 10
      clots with only 1 of the 10 showing evidence of bleeding. In all cases,
      thrombolysis occurred only in the presence of cavitation. CONCLUSION: High
      intensity focused ultrasound thrombolysis is feasible as a means of restoring
      partial blood flow in thrombus-occluded arteries in the absence of thrombolytic
      agents. The potential for bleeding with this approach requires further
      investigation.

PMID- 22373535
TI  - Development and fine-tuning of a scale down model for process characterization
      studies of a monoclonal antibody upstream production process.

PMID- 22373536
TI  - Association screening for genes with multiple potentially rare variants: an
      inverse-probability weighted clustering approach.
AB  - Both common variants and rare variants are involved in the etiology of most
      complex diseases in humans. Developments in sequencing technology have led to the
      identification of a high density of rare variant single-nucleotide polymorphisms
      (SNPs) on the genome, each of which affects only at most 1% of the population.
      Genotypes derived from these SNPs allow one to study the involvement of rare
      variants in common human disorders. Here, we propose an association screening
      approach that treats genes as units of analysis. SNPs within a gene are used to
      create partitions of individuals, and inverse-probability weighting is used to
      overweight genotypic differences observed on rare variants. Association between a
      phenotype trait and the constructed partition is then evaluated. We consider
      three association tests (one-way ANOVA, chi-square test, and the partition
      retention method) and compare these strategies using the simulated data from the
      Genetic Analysis Workshop 17. Several genes that contain causal SNPs were
      identified by the proposed method as top genes.

PMID- 22373537
TI  - Using LASSO regression to detect predictive aggregate effects in genetic studies.
AB  - We use least absolute shrinkage and selection operator (LASSO) regression to
      select genetic markers and phenotypic features that are most informative with
      respect to a trait of interest. We compare several strategies for applying LASSO
      methods in risk prediction models, using the Genetic Analysis Workshop 17 exome
      simulation data consisting of 697 individuals with information on genotypic and
      phenotypic features (smoking, age, sex) in 5-fold cross-validated fashion. The
      cross-validated averages of the area under the receiver operating curve range
      from 0.45 to 0.63 for different strategies using only genotypic markers. The same
      values are improved to 0.69-0.87 when both genotypic and phenotypic information
      are used. The ability of the LASSO method to find true causal markers is limited,
      but the method was able to discover several common variants (e.g., FLT1) under
      certain conditions.

PMID- 22373538
TI  - Expression and localization of claudins-3 and -12 in transformed human brain
      endothelium.
AB  - BACKGROUND: The aim of this study was to characterize the hCMEC/D3 cell line, an
      in vitro model of the human Blood Brain Barrier (BBB) for the expression of brain
      endothelial specific claudins-3 and -12. FINDINGS: hCMEC/D3 cells express
      claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin 
      12 is observed in the perinuclear region and completely absent from TJs. We show
      that the expression of both proteins is lost in cell passage numbers where the
      BBB properties are no longer fully conserved. Expression and localization of
      claudin-3 is not modulated by simvastatin shown to improve barrier function in
      vitro and also recommended for routine hCMEC/D3 culture. CONCLUSIONS: These
      results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell
      line and make claudin-3 a potential marker for BBB characteristics in vitro.

PMID- 22373539
TI  - European cancer mortality predictions for the year 2012.
AB  - BACKGROUND: Estimating current cancer mortality figures is important for defining
      priorities for prevention and treatment. MATERIALS AND METHODS: Using logarithmic
      Poisson count data joinpoint models on mortality and population data from the
      World Health Organization database, we estimated numbers of deaths and age
      standardized rates in 2012 from all cancers and selected cancer sites for the
      whole European Union (EU) and its six more populated countries. RESULTS: Cancer
      deaths in the EU in 2012 are estimated to be 1,283,101 (717,398 men and 565,703
      women) corresponding to standardized overall cancer death rates of 139/100,000
      men and 85/100,000 women. The fall from 2007 was 10% in men and 7% in women. In
      men, declines are predicted for stomach (-20%), leukemias (-11%), lung and
      prostate (-10%) and colorectal (-7%) cancers, and for stomach (-23%), leukemias (
      12%), uterus and colorectum (-11%) and breast (-9%) in women. Almost stable rates
      are expected for pancreatic cancer (+2-3%) and increases for female lung cancer
      (+7%). Younger women show the greatest falls in breast cancer mortality rates in
      the EU (-17%), and declines are expected in all individual countries, except
      Poland. CONCLUSION: Apart for lung cancer in women and pancreatic cancer,
      continuing falls are expected in mortality from major cancers in the EU.

PMID- 22373540
TI  - Methods for detecting associations between phenotype and aggregations of rare
      variants.
AB  - Although genome-wide association studies have uncovered variants associated with
      more than 150 traits, the percentage of phenotypic variation explained by these
      associations remains small. This has led to the search for the dark matter that
      explains this missing genetic component of heritability. One potential
      explanation for dark matter is rare variants, and several statistics have been
      devised to detect associations resulting from aggregations of rare variants in
      relatively short regions of interest, such as candidate genes. In this paper we
      investigate the feasibility of extending this approach in an agnostic way, in
      which we consider all variants within a much broader region of interest, such as
      an entire chromosome or even the entire exome. Our method searches for subsets of
      variant sites using either Markov chain Monte Carlo or genetic algorithms. The
      analysis was performed with knowledge of the Genetic Analysis Workshop 17
      answers.

PMID- 22373541
TI  - Effects of assisted and variable mechanical ventilation on cardiorespiratory
      interactions in anesthetized pigs.
AB  - The physiological importance of respiratory sinus arrhythmia (RSA) and
      cardioventilatory coupling (CVC) has not yet been fully elucidated, but these
      phenomena might contribute to improve ventilation/perfusion matching, with
      beneficial effects on gas exchange. Furthermore, decreased RSA amplitude has been
      suggested as an indicator of impaired autonomic control and poor clinical
      outcome, also during positive-pressure mechanical ventilation (MV). However, it
      is currently unknown how different modes of MV, including variable tidal volumes
      (V(T)), affect RSA and CVC during anesthesia. We compared the effects of pressure
      controlled (PCV) versus pressure assisted (PSV) ventilation, and of random
      variable versus constant V(T), on RSA and CVC in eight anesthetized pigs. At
      comparable depth of anesthesia, global hemodynamics, and ventilation, RSA
      amplitude increased from 20 ms in PCV to 50 ms in PSV (p < 0.05). CVC was
      detected (using proportional Shannon entropy of the interval between each
      inspiration onset and the previous R-peak in ECG) in two animals in PCV and seven
      animals in PSV. Variable V(T) did not significantly influence these phenomena.
      Furthermore, heart period and systolic arterial pressure oscillations were in
      phase during PCV but in counter-phase during PSV. At the same depth of anesthesia
      in pigs, PSV increases RSA amplitude and CVC compared to PCV. Our data suggest
      that the central respiratory drive, but not the baroreflex or the mechano
      electric feedback in the heart, is the main mechanism behind the RSA increase.
      Hence, differences in RSA and CVC between mechanically ventilated patients might
      reflect the difference in ventilation mode rather than autonomic impairment.
      Also, since gas exchange did not increase from PCV to PSV, it is questionable
      whether RSA has any significance in improving ventilation/perfusion matching
      during MV.

PMID- 22373542
TI  - Antioxidant, antimicrobial, and theoretical studies of the thiosemicarbazone
      derivative Schiff base 2-(2-imino-1-methylimidazolidin-4
      ylidene)hydrazinecarbothioamide (IMHC).
AB  - BACKGROUND: Adverse antimicrobial activities of thiosemicarbazone (TSC) and
      Schiff base derivatives have widely been studied by using different kinds of
      microbes, in addition different methods were used to assay the antioxidant
      activities using DPPH, peroxids, or ntrosyl methods. However, there are no
      studies describing the synthesis of TSC derived from creatinine. RESULTS: In this
      study, 2-(2-imino-1-methylimidazolidin-4-ylidene)hydrazinecarbothioamide (IMHC)
      was synthesized by the reaction of creatinine with thiosemicarbazide. The novel
      molecule was characterized by FT-IR, UV-VIS, and NMR spectra in addition of the
      elemental analysis. The free radical scavenging ability of the IMHC was
      determined by it interaction with the stable-free radical 2,2"-diphenyl-1
      picrylhydrazyl (or nitric oxide or hydrogen peroxide) and showed encouraging
      antioxidant activities. Density functional theory calculations of the IMHC
      performed using molecular structures with optimized geometries. Molecular orbital
      calculations provide a detailed description of the orbitals, including spatial
      characteristics, nodal patterns, and the contributions of individual atoms.
      Highest occupied molecular orbital-lowest unoccupied molecular orbital energies
      and structures are shown. CONCLUSIONS: IMHC shows considerable antibacterial and
      antifungal activities. The free radical scavenging activity of synthesized
      compound was screened for in vitro antioxidant activity.

PMID- 22373543
TI  - Parental perceptions of the roles of home and school in health education for
      elementary school children in Finland.
AB  - A variety of legislation, initiatives and organizations exist to support,
      encourage and even oblige schools to collaborate more effectively with parents or
      guardians. However, there is minimal understanding of the experiences and
      opinions of parents and school staff about their roles, especially in relation to
      children's health education. This study examined how parents of 10-11-year-old
      children perceive the roles of both home and school in educating children about
      health. A questionnaire, based partly on the Finnish national core curriculum for
      basic education, was administered to 348 parents; the response rate was 53%.
      Factor analysis was used to define sum variables, which were then used as
      dependent variables in an analysis of variance examining the effects of
      children's gender and health; parents' education, gender, work status and year of
      birth; and school location (urban/rural). The results suggested that parents
      considered that either health education was mainly their responsibility, or it
      was a mutual responsibility with the school. Parents living in rural areas and
      the youngest group of parents were more likely to consider that health education
      should be shared with schools than were parents living in cities, or older
      parents. To expand awareness about the role of home and school in children's
      health education and to develop further health promotion within the whole school
      community, it is important to gather parents' views regarding health issues. This
      study was conducted as part of a broader program in the health promotion network
      of the Schools for Health in Europe (SHE).

PMID- 22373544
TI  - 3D-QSAR study indicates an enhancing effect of membrane ions on psychiatric drugs
      targeting serotonin receptor 5-HT1A.
AB  - Antidepressants and antipsychotics are psychiatric agents used for the treatment
      of various types of psychiatric diseases. Although currently among the most
      commonly prescribed drugs, their effectiveness and adverse effects are the topic
      of many studies and controversial claims. Here we generate QSAR models based on
      compounds series including 20 drugs recommended for two critical psychiatric
      diseases: depression and schizophrenia and we use these QSAR models to predict
      the biological activity of these 20 antidepressants and antipsychotics. We
      establish the membrane ions' contributions (sodium, potassium, calcium and iron)
      mediated by water to the antagonism of these drugs at the 5-HT1A receptor. The
      reliability of our QSAR models in predicting compounds activity is indicated by
      significant values for cross-validated correlation q2 (0.60-0.76) and fitted
      correlation r2 (0.96-0.98) coefficients. Our results indicate that potassium,
      calcium and iron play a key role for the antagonistic activity of drugs at the 5
      HT1A receptor. Moreover, based on the established QSAR equations, we analysed 24
      new escitalopram derivatives as possibly improved antidepressants targeting the 5
      HT1A receptor. We identified that the presence of methyl groups and hydrogen
      atoms improves antidepressant activity while the simultaneous presence of ethyl,
      propyl or halogens decreased drastically antidepressant activity at the 5-HT1A
      site.

PMID- 22373545
TI  - Systematic fragmentation of large molecules by annihilation.
AB  - A new version of systematic molecular fragmentation is presented which provides a
      hierarchy of estimates for the energy, and other properties, of large molecules
      with a computation time that scales linearly with the size of the molecule. This
      method is combined with an algorithm which ensures that the evaluation of the
      fragment compositions is efficient for very large molecules. The method is
      illustrated using protein structures derived from NMR spectroscopy.

PMID- 22373546
TI  - Bismuth(III) triflate promoted intramolecular hydroamination of unactivated
      alkenyl sulfonamides in the preparation of pyrrolidines.
AB  - Bi(OTf)(3).nH(2)O was found to be an efficient promoter of the cyclisative
      hydroamination of unactivated alkenyl sulfonamides, giving rise to the N
      protected 2-methyl pyrrolidines in good to excellent yields (up to 95%). Based on
      control experiments, a joint Lewis acid-Bronsted acid catalysis might be in
      operation, or triflic acid itself, generated in situ by hydrolysis of metal
      triflate, could be the true hydroamination catalyst.

PMID- 22373547
TI  - High level expression of bikunin in Pichia pastoris by fusion of human serum
      albumin.
AB  - Bikunin is a proteoglycan exhibiting broad-spectrum inhibitory activity against
      serine proteases and could potentially suppress tumor cell invasion and
      metastasis. Here, we have successfully expressed recombinant human bikunin (rh
      bikunin) in Pichia pastoris and also established the purification procedure.
      Different fusion genes of h-UTI and domain I, domain I and domain II, domain I,
      domain II and domain III of human serum albumin (HSA) were inserted into
      expression vector pPICZalphaA. After expressed in shake flask, rh-bikunin was
      produced in an 30-L fermenter and purified by affinity chromatography and cation
      exchange chromatography. The final expression levels were 200 mg/L and we got
      totally 1.08 g (3650 IU/mg) of active purified rh-bikunin (purity is 98%) from 20
      L of fermentation broth. The rh-bikunin consists of unique form with molecular
      masses of 25 kDa, and has the same N-terminals sequence as human native bikunin.
      This study provided a new method for high level expression of active rh-bikunin
      by using HSA as fusion parter.

PMID- 22373548
TI  - Rejuvenating liver and pancreas through cell transdifferentiation.

PMID- 22373549
TI  - Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.
AB  - ETV6 is an important hematopoietic regulatory factor and ETV6 gene rearrangement
      is involved in a wide variety of hematological malignancies. In this study, we
      sought to investigate the incidence of ETV6-associated fusion genes in B- and T
      lineage acute lymphoblastic leukemia (ALL) by multiplex-nested reverse
      transcription-polymerase chain reaction (RT-PCR) in 176 adult ALL patients. Total
      RNA was extracted from bone marrow samples of ALL patients including 136 B- and
      40 T-lineage ALL, and ETV6 fusion genes were detected by multiplex-nested RT-PCR.
      Changes of ETV6 fusion gene mRNA transcript levels were examined by real-time RT
      PCR. We detected a total of 15 ETV6 gene rearrangements with a positive rate of
      8.5%, involving seven ETV6-associated fusion genes in 13 B-ALL (13/136, 9.6%) and
      2 T-ALL patients (2/40, 5.0%). ETV6-RUNX1 were observed in six cases (3.4%), ETV6
      JAK2 in three cases (1.7%), ETV6-ABL1 in two cases (1.1%), and ETV6-ABL2, ETV6
      NCOA2, ETV6-SYK, and PAX5-ETV6 each in one case (0.6%). ETV6-JAK2 was found in
      both B-ALL and T-ALL patients. Furthermore, real-time quantitative RT-PCR assays
      showed that the ETV6-RUNX1 mRNA transcript levels decreased during conventional
      chemotherapy or hematopoietic stem cell transplantation. This study shows that
      multiplex-nested RT-PCR is an effective and accurate tool to identify ETV6
      rearrangements in adult ALL, which provides some clues into the diagnosis and
      prognosis of ALL but also molecular markers for the detection of minimal residual
      disease in adult ALL.

PMID- 22373550
TI  - Serum beta2-microglobin is a predictor of prognosis in patients with upper
      aerodigestive tract NK/T-cell lymphoma.
AB  - Upper aerodigestive tract natural killer (NK)/T-cell lymphoma (UNKTL) is the most
      common type of extranodal NK/T-cell lymphoma, nasal type. Serum beta2
      microglobulin (beta2-M) was found to be a predictor in some subtypes of B-cell
      lymphoma. However, its prognostic significance in NK/T-cell lymphoma has never
      been explored. We retrospectively analyzed 82 patients newly diagnosed as UNKTL.
      Serum beta2-M was detected prior to treatment in this series. Various statistical
      analyses were performed to evaluate the significance of the relevant clinical
      parameters. High serum beta2-M level was calculated as >=2.5 mg/L by the median
      value. The number of patients with serum beta2-M >=2.5 mg/L at diagnosis was 39
      (47.6%) and 43 patients (52.4%) with beta2-M <2.5 mg/L. Patients with high serum
      beta2-M level at diagnosis seemed to have more adverse clinical features: B
      symptoms (p=0.007) and elevated LDH level (p<0.001), and high KPI score
      (p=0.002). Serum beta2-M >=2.5 mg/L was significantly associated with poor
      overall survival (5-year OS, 35.2% vs 73.6%; p=0.001) and progression-free
      survival (5-year PFS, 27.5% vs 55.9%; p=0.028). For patients with early stage,
      serum beta2-M at diagnosis could also help to distinguish those with favorable
      outcomes from those with poor outcomes. In multivariate analysis, high serum
      beta2-M level remained its prognostic impact on survival (OS: p=0.002; PFS:
      p=0.039), independent of the International Prognostic Index score. Our study
      suggested high serum beta2-M was a novel predictor of prognosis in patients with
      UNKTL. A simply and regular way might be established to identify UNKTL patients
      of different risks at diagnosis.

PMID- 22373551
TI  - Spontaneous remission after a year of romiplostim in an adult patient with
      refractory primary immune thrombocytopenia.

PMID- 22373552
TI  - [Dysphagia in Avellis' syndrome].
AB  - BACKGROUND: Avellis' syndrome (lateral medulla oblongata ischaemia) is a rare
      neurological disorder. Early recognition of brain stem infarction may prevent
      referral to specialists other than a neurologist. CASE DESCRIPTION: A 53-year-old
      woman was initially presented to an internist with acute onset of headache,
      dysphagia, nausea and vomiting. She was also hoarse and had a tingling feeling on
      the left side of her face, and in her left arm and leg. A neurologist was
      consulted and diagnosed Avellis' syndrome. MRI of the brain revealed ischaemia in
      the lateral medulla oblongata on the right side. CONCLUSION: Brain stem
      infarction may be hard to recognize as lateralization is often less predominant
      than in hemispheric syndromes. In acute onset of dysphagia, the differential
      diagnosis should always include brain stem infarction.

PMID- 22373553
TI  - [The stepped wedge design].
AB  - Not all questions concerning therapeutic effects in medical research can be
      answered satisfactorily by standard trials. The stepped wedge cluster design is a
      special form of randomised study in which an intervention at group level is
      implemented in stages. The design can be used in situations where randomization
      at the patient level is inappropriate or impossible and where a stepped
      implementation of the experimental intervention is important for ethical,
      logistic or financial reasons. The time before the experimental intervention is
      introduced in a cluster is used as control period. The statistical analysis of
      cluster trials should account for the fact that individuals within clusters may
      show many similarities. Ethical aspects of stepped wedge design should be
      considered carefully, especially when obtaining individual informed consent is
      not possible.

PMID- 22373554
TI  - [Care for survivors of childhood cancer in the Netherlands].
AB  - Survival of childhood cancer has improved resulting in an increasing number of
      survivors who are at high risk of developing treatment-related health problems.
      The authors emphasize the need for specialized care for survivors of childhood
      cancer by describing three patients who all developed late effects of treatment.
      The first patient, a 32-year-old female, who had several late effects caused by
      treatment for nephroblastoma; the second  a 39-year-old female, who developed
      breast cancer after thoracic irradiation for metastatic nephroblastoma; the third
      a 45-year-old female diagnosed with a meningioma caused by cranial irradiation
      for acute lymphoblastic leukaemia. In the Netherlands medical care for survivors
      is clustered at special outpatient clinics (in Dutch: Langetermijneffecten na
      kinderkanker (Long-term effects after childhood cancer; LATER)-outpatient
      clinics). In 2010 a guideline was published with recommendations for optimal
      follow-up and care for survivors of childhood cancer.

PMID- 22373556
TI  - [One episode of cancer, always a patient].
AB  - Two articles in this issue of the Dutch Journal of Medicine address the issue of
      the long-term consequences of cancer treatment. They show the serious long-term
      side effects of oncological interventions on the quality of life and the medical
      future of surviving cancer patients, and emphasize the need for a nationwide
      early detection program that effectively picks up those patients suffering from
      the complications of oncological treatment. New systematic follow-up programs
      hold the promise of successfully detecting those patients with physical problems
      due to their oncological history. They also clearly show that long-term sequelae
      of successful oncological treatment will become a more frequently-encountered
      medical problem in a rapidly increasing number of "ex" patients. Not only
      physicians, but also insurance companies and medical authorities should address
      the change in the medical requirements of this new type of patient with very
      specific medical problems.

PMID- 22373558
TI  - [Consequences of non-alcoholic fatty liver disease still unclear].
AB  - There is still a lack of clarity concerning the long-term outcome and severity of
      non-alcoholic fatty liver disease (NAFLD). Results of a study recently conducted
      by the National Health and Nutrition Examination Survey (NHANES) showed that
      patients with NAFLD diagnosed 30 years ago did not experience decreased survival
      when compared with persons without NAFLD. But questions arise about the
      diagnostic methods in this study and the consequences for daily practice. Is
      NAFLD really a disease, and what is the diagnostic method of choice?

PMID- 22373560
TI  - Changes in inhibitory CA1 network in dual pathology model of epilepsy.
AB  - The combination of two precipitating factors appears to be more and more
      recognized in patients with temporal lobe epilepsy. Using a two-hit rat model,
      with a neonatal freeze lesion mimicking a focal cortical malformation combined
      with hyperthermia-induced seizures mimicking febrile seizures, we have previously
      reported an increase of inhibition in CA1 pyramidal cells at P20. Here, we
      investigated the changes affecting excitatory and inhibitory drive onto CA1
      interneurons to better define the changes in CA1 inhibitory networks and their
      paradoxical role in epileptogenesis, using electrophysiological recordings in CA1
      hippocampus from rat pups (16-20 d old). We investigated interneurons in CA1
      hippocampal area located in stratum oriens (Or) and at the border of strata
      lacunosum and moleculare (L-M). Our results revealed an increase of the
      excitatory drive to both types of interneurons with no change in the inhibitory
      drive. The mechanisms underlying the increase of excitatory synaptic currents
      (EPSCs) in both types of interneurons are different. In Or interneurons, the
      amplitude of spontaneous and miniature EPSCs increased, while their frequency was
      not affected suggesting changes at the post-synaptic level. In L-M interneurons,
      the frequency of spontaneous EPSCs increases, but the amplitude is not affected.
      Analyses of miniature EPSCs showed no changes in both their frequency and
      amplitude. We concluded that L-M interneurons increase in excitatory drive is due
      to a change in Shaffer collateral axon excitability. The changes described here
      in CA1 inhibitory network may actually contribute to the epileptogenicity
      observed in this dual pathology model by increasing pyramidal cell
      synchronization.

PMID- 22373559
TI  - Disruption of NMDAR-CRMP-2 signaling protects against focal cerebral ischemic
      damage in the rat middle cerebral artery occlusion model.
AB  - Collapsin response mediator protein 2 (CRMP-2), traditionally viewed as an
      axon/dendrite specification and axonal growth protein, has emerged as nidus in
      regulation of both pre- and post-synaptic Ca ( 2+) channels. Building on our
      discovery of the interaction and regulation of Ca ( 2+) channels by CRMP-2, we
      recently identified a short sequence in CRMP-2 which, when appended to the
      transduction domain of HIV TAT protein, suppressed acute, inflammatory and
      neuropathic pain in vivo by functionally uncoupling CRMP-2 from the Ca ( 2+)
      channel. Remarkably, we also found that this region attenuated Ca ( 2+) influx
      via N-methylD-Aspartate receptors (NMDARs) and reduced neuronal death in a
      moderate controlled cortical impact model of traumatic brain injury (TBI). Here,
      we sought to extend these findings by examining additional neuroprotective
      effects of this peptide (TAT-CBD3) and exploring the biochemical mechanisms by
      which TAT-CBD3 targets NMDARs. We observed that an intraperitoneal injection of
      TAT-CBD3 peptide significantly reduced infarct volume in an animal model of focal
      cerebral ischemia. Neuroprotection was observed when TAT-CBD3 peptide was given
      either prior to or after occlusion but just prior to reperfusion. Surprisingly, a
      direct biochemical complex was not resolvable between the NMDAR subunit NR2B and
      CRMP-2. Intracellular application of TAT-CBD3 failed to inhibit NMDAR current.
      NR2B interactions with the post synaptic density protein 95 (PSD-95) remained
      intact and were not disrupted by TAT-CBD3. Peptide tiling of intracellular
      regions of NR2B revealed two 15-mer sequences, in the carboxyl-terminus of NR2B,
      that may confer binding between NR2B and CRMP-2 which supports CRMP-2's role in
      excitotoxicity and neuroprotection.

PMID- 22373561
TI  - Effect of automatic image realignment on visuomotor coordination in simulated
      laparoscopic surgery.
AB  - During laparoscopic surgery, the surgeon's hand-eye coordination is often
      disrupted by the incongruent mapping between the orientation of the endoscopic
      view and the actual operative field. Two experiments were conducted to examine
      the effect of automatic image realignment on the performance of laparoscopic
      surgery. The first experiment investigated how visual-motor misalignment impacted
      laparoscopic surgery performance. Novice subjects were randomly assigned to one
      of the two paired viewing conditions in a simulated laparoscopic surgery
      environment: 1) the endoscope was either at the center of the modeled workspace
      with an optical axis of 90 degrees , or at -45 degrees  from the midline of the
      subjects with an optical axis 45 degrees ; 2) the endoscope was either at 0
      degrees , or at 180 degrees  from the midline of the subjects, both with an
      optical axis of 45 degrees . Each group of twelve subjects performed a dynamic
      point-and-touch task under the assigned pair of viewing conditions, each with
      eight image orientations, in a repeated-measures mixed design. The second
      experiment examined whether the automatic realigning mechanism that was activated
      mid-task (such that a congruent mapping between display and control was re
      established if the mapping at the beginning of the task had been misaligned) was
      helpful to improve performance. Twelve novice subjects performed the same task as
      in the first experiment in a repeated-measures design. Performance was examined
      under three misaligned visuomotor mappings, each followed by the realigned
      mapping activated by the automatic realigning mechanism. Results showed that
      performance was best when the endoscopic image was perfectly aligned with the
      actual task space (0 degrees  image orientation), but degraded progressively as a
      function of deviation from perfect alignment. Subjects' performance maintained a
      consistent pattern across 8 image orientations regardless of optical axis
      orientation and endoscope location. Performance was improved with the automatic
      realigning mechanism. It is recommended that any solution to restore the
      visuomotor congruency in laparoscopic surgery should first align the image with
      the task space. This work has implications for the design of visualization
      systems in laparoscopic surgery.

PMID- 22373562
TI  - Long-term outcome of breast conserving therapy.

PMID- 22373563
TI  - Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year
      follow-up of the EORTC 10801 phase 3 randomised trial.
AB  - BACKGROUND: The EORTC 10801 trial compared breast-conserving therapy (BCT) with
      modified radical mastectomy (MRM) in patients with tumours 5 cm or smaller and
      axillary node negative or positive disease. Compared with BCT, MRM resulted in
      better local control, but did not affect overall survival or time to distant
      metastases. We report 20-year follow-up results. METHODS: The EORTC 10801 trial
      was open for accrual between 1980 and 1986 in eight centres in the UK, the
      Netherlands, Belgium, and South Africa. 448 patients were randomised to BCT and
      420 to MRM. Randomisation was done centrally, stratifying patients by institute,
      carcinoma stage (I or II), and menopausal status. BCT comprised of lumpectomy and
      complete axillary clearance, followed by breast radiotherapy and a tumour-bed
      boost. The primary endpoint was time to distant metastasis. This analysis was
      done on all eligible patients, as they were randomised. FINDINGS: After a median
      follow-up of 22.1 years (IQR 18.5-23.8), 175 patients (42%) had distant
      metastases in the MRM group versus 207 (46%) in the BCT group. Furthermore, 506
      patients (58%) died (232 [55%] in the MRM group and 274 [61%] in the BCT group).
      No significant difference was observed between BCT and MRM for time to distant
      metastases (hazard ratio 1.13, 95% CI 0.92-1.38; p=0.23) or for time to death
      (1.11, 0.94-1.33; 0.23). Cumulative incidence of distant metastases at 20 years
      was 42.6% (95% CI 37.8-47.5) in the MRM group and 46.9% (42.2-51.6) in the BCT
      group. 20-year overall survival was estimated to be 44.5% (95% CI 39.3-49.5) in
      the MRM group and 39.1% (34.4-43.9) in the BCT group. There was no difference
      between the groups in time to distant metastases or overall survival by age (time
      to distant metastases: <50 years 1.09 [95% CI 0.79-1.51] vs >=50 years 1.16 [0.90
      1.50]; overall survival <50 years 1.17 [0.86-1.59] vs >=50 years 1.10 [0.89
      1.37]). INTERPRETATION: BCT, including radiotherapy, offered as standard care to
      patients with early breast cancer seems to be justified, since long-term follow
      up in this trial showed similar survival to that after mastectomy. FUNDING:
      European Organisation for Research and Treatment of Cancer (EORTC).

PMID- 22373564
TI  - Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in
      aldosteronism.
AB  - Aldosteronism, or chronic elevation in plasma aldosterone (ALDO) (inappropriate
      for dietary Na(+) intake), is accompanied by an adverse structural remodeling of
      the heart and vasculature. Herein, we bring forward a new perspective in which
      parathyroid hormone (PTH) is identified as a crucial mediator of pathologic
      cardiac remodeling in aldosteronism. Secondary hyperparathyroidism (SHPT) appears
      because of the marked urinary and fecal losses of Ca(2+) and Mg(2+) that
      accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia,
      providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked
      to restore extracellular Ca(2+) and Mg(2+) homeostasis, elevations in plasma PTH
      lead to paradoxical intracellular Ca(2+) overloading of diverse tissues. In the
      case of cardiomyocytes, the excessive intracellular Ca(2+) accumulation involves
      both cytosolic free and mitochondrial domains with a consequent induction of
      oxidative stress by these organelles and lost ATP synthesis. The ensuing opening
      of their inner membrane permeability transition pore (mPTP) accounts for the
      osmotic swelling and structural degeneration of mitochondria followed by
      programed cell necrosis. Tissue repair, invoked to preserve the structural
      integrity of myocardium accounts for a replacement fibrosis, or scarring, which
      is found scattered throughout the right and left heart; it represents a
      morphologic footprint of earlier necrosis. Multiple lines of evidence are
      reviewed that substantiate the PTH-mediated paradigm and the mitochondriocentric
      signal-transducer-effector pathway to cardiomyocyte necrosis.

PMID- 22373565
TI  - Percutaneous method for single-catheter multiple monophasic action potential
      recordings during magnetocardiographic mapping in spontaneously breathing
      rodents.
AB  - To test the feasibility of a novel method to combine magnetocardiographic (MCG)
      estimate of ventricular repolarization (VR) and multiple monophasic action
      potential (MultiMAP) recording in spontaneously breathing rodents with
      percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic
      catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied.
      Under fluoroscopic control, the AC was moved until four stable MAPs were recorded
      (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20
      fT Hz(-1/2)) were used for MCG mapping. MAPs, differentially amplified (BW: DC
      500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective
      refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and
      90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording
      were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs
      than in GPs (26.4 +/- 2.9 ms versus 110.6 +/- 14.3 ms and 60.7 +/- 5.4 ms versus
      127.7 +/- 15.3 ms, respectively). VERP was 51 +/- 4.8 ms in WRs and 108.4 +/-
      12.9 ms in GPs, respectively. The MAP amplitude was 16.9 +/- 4.5 in WRs and 16.2
      +/- 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals
      survived the procedure. Two also survived a second invasive study; one was
      followed up until natural death at 52 months. Percutaneous MultiMAP recording is
      minimally invasive, usually avoids animal sacrifice, is compatible with
      simultaneous surface MCG mapping and might be used for experimental validation of
      MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or
      animal models of ventricular arrhythmias.

PMID- 22373566
TI  - A gene-based approach for testing association of rare alleles.
AB  - Rare genetic variants have been shown to be important to the susceptibility of
      common human diseases. Methods for detecting association of rare genetic variants
      are drawing much attention. In this report, we applied a gene-based approach to
      the 200 simulated data sets of unrelated individuals. The test can detect the
      association of some genes with multiple rare variants.

PMID- 22373567
TI  - PKC phosphorylates GluA1-Ser831 to enhance AMPA receptor conductance.
AB  - AMPA receptors mediate fast excitatory synaptic transmission in the brain, and
      are dynamically regulated by phosphorylation of multiple residues within the C
      terminal domain. CaMKII phosphorylates Ser831 within the AMPA receptor GluA1
      subunit to increase single channel conductance, and biochemical studies show that
      PKC can also phosphorylate this residue. In light of the discovery of additional
      PKC phosphorylation sites within the GluA1 C-terminus, it remains unclear whether
      PKC phosphorylation of Ser831 increases GluA1 conductance in intact receptors.
      Here, we report that the purified, catalytic subunit of PKC significantly
      increases the conductance of wild-type GluA1 AMPA receptors expressed in the
      presence of stargazin in HEK293T cells. Furthermore, the mutation GluA1-S831A
      blocks the functional effect of PKC. These findings suggest that GluA1 AMPA
      receptor conductance can be increased by activated CaMKII or PKC, and that
      phosphorylation at this site provides a mechanism for channel modulation via a
      variety of protein signaling cascades.

PMID- 22373568
TI  - The impact of aging on the brain--risk, resilience and repair.

PMID- 22373569
TI  - Occurrence of GCH1 gene mutations in a group of Indian dystonia patients.
AB  - The aim of this study is to examine the role of GCH1 among Indians affected with
      dopa responsive dystonia (DRD) and early onset Parkinson's disease (EOPD). The
      patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were
      screened for variants in GCH1 by PCR amplification of exons, splice junctions and
      1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants
      (p.Met1Val, p.Val204_205del, IVS3+68A>G, and IVS5-6T>G) were identified in 10
      patients but not in the controls. In addition to two nonsynonymous changes,
      identified in four DRD patients in heterozygous condition, one intronic variant
      (IVS5-6T>G) could be linked to pathogenesis of the disease since it has the
      potential of altering the splice site as assessed by in silico analysis. Patients
      carrying different nonsynonymous variants had remarkable variation in clinical
      phenotype. Consistent with earlier reports, severity of clinical phenotype and
      the age of onset varied among family members harboring the same mutation. No
      mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene
      have been found and are shown to be associated with variable clinical phenotypes
      mostly within the spectrum of DRD. The mutations identified represent 15.79%
      (3/19) of east Indian DRD patient cohort.

PMID- 22373570
TI  - Inhibitory effect of sour pomegranate sauces on some green vegetables and kisir.
AB  - In this study, the antimicrobial effects of both traditional and commercial
      pomegranate sour sauce samples on some green vegetables and also on "kisir" which
      is a popular and traditional appetizer in Turkey were investigated. The
      inhibitory effect of the pomegranate products on the naturally existing bacterial
      microflora of lettuce, spring onion, parsley and kisir were analyzed. Also, all
      these food samples were inoculated with Staphylococcus aureus (ATCC-25923) and
      Escherichia coli O157:H7 (ATCC-43895) and antimicrobial effect of the pomegranate
      products on the inoculated microflora was detected. All the food samples were
      treated with pomegranate products for different time periods and the effect of
      treatment time was investigated. pH and titratable acidity values of the
      traditional and commercial pomegranate sour sauce samples were detected. The
      results showed that although the pomegranate products had an antimicrobial effect
      on the natural bacterial microflora of the food samples, the effect on inoculated
      food samples was more prominent and additionally the application time was found
      to be a crucial parameter for both cases.

PMID- 22373571
TI  - Growth/no growth interfaces of table olive related yeasts for natamycin, citric
      acid and sodium chloride.
AB  - The present work uses a logistic/probabilistic model to obtain the growth/no
      growth interfaces of Saccharomyces cerevisiae, Wickerhamomyces anomalus and
      Candida boidinii (three yeast species commonly isolated from table olives) as a
      function of the diverse combinations of natamycin (0-30 mg/L), citric acid (0.00
      0.45%) and sodium chloride (3-6%). Mathematical models obtained individually for
      each yeast species showed that progressive concentrations of citric acid
      decreased the effect of natamycin, which was only observed below 0.15% citric
      acid. Sodium chloride concentrations around 5% slightly increased S. cerevisiae
      and C. boidinii resistance to natamycin, although concentrations above 6% of NaCl
      always favoured inhibition by this antimycotic. An overall growth/no growth
      interface, built considering data from the three yeast species, revealed that
      inhibition in the absence of citric acid and at 4.5% NaCl can be reached using
      natamycin concentrations between 12 and 30 mg/L for growth probabilities between
      0.10 and 0.01, respectively. Results obtained in this survey show that is not
      advisable to use jointly natamycin and citric acid in table olive packaging
      because of the observed antagonistic effects between both preservatives, but
      table olives processed without citric acid could allow the application of the
      antifungal.

PMID- 22373572
TI  - Soya isoflavone consumption in relation to carotid intima-media thickness in
      Chinese equol excretors aged 40-65 years.
AB  - Previous studies have suggested that the daidzein metabolite equol rather than
      daidzein itself contributes to the beneficial effect of soya foods in the
      prevention of CVD. The aim of the present study is to examine the proportion of
      equol excretion in Chinese adults and compare plasma lipids and carotid artery
      intima-media thickness (IMT) between equol excretors and non-excretors, and to
      evaluate the effect of soya isoflavone intakes on serum lipids and IMT in either
      equol excretors or non-excretors. Subjects (n 572; women n 362, men n 210) were
      recruited for the present study. An overnight urine sample was provided by each
      subject on their usual diet to quantify urinary concentrations of daidzein and
      equol. Far-wall IMT was determined by B-mode ultrasound in the right carotid at
      two sites, carotid bulb (CB-IMT) and common carotid artery (CCA-IMT), and fasting
      serum lipids were measured. Habitual dietary intakes were estimated with a FFQ,
      and soya isoflavone intake derived from the FFQ was assessed. Of the 572
      subjects, the proportion of equol excretors on their usual diet was 25.0 % (n
      143). Compared with non-excretors, equol excretors showed significantly lower
      serum TAG (-38.2 (95 % CI -70.4, -5.9) %, P = 0.012) and CCA-IMT (-4.9 (95 % CI 
      9.7, -0.3) %, P = 0.033). Equol excretors with higher daily isoflavone intakes (
      5.4 mg/d) had significantly lower IMT (-16.2 %, P = 0.035) and tended to have
      higher HDL-cholesterol (P = 0.055) than did those with lower daily isoflavone
      intakes (1.5 mg/d), while no association was observed between soya isoflavone
      intakes and serum lipids or IMT in non-excretors. In conclusion, the benefits of
      soya isoflavones in preventing CVD may be apparent among equol excretors only.

PMID- 22373573
TI  - Exploring Forster electronic energy transfer in a decoupled anthracenyl-based
      borondipyrromethene (bodipy) dyad.
AB  - An anthracenyl-Bodipy dyad containing a triazole bridge, that acts to decouple
      the two units in the ground state, has been synthesised and structurally
      characterised. Efficient electronic energy transfer occurs from the anthracenyl
      based unit to the Bodipy system in toluene in around 12 ps, and becomes faster in
      solvents of lower refractive index. The rate of electronic energy transfer is
      discussed in terms of Forster theory.

PMID- 22373574
TI  - NLK positively regulates Wnt/beta-catenin signalling by phosphorylating LEF1 in
      neural progenitor cells.
AB  - Nemo-like kinase (NLK/Nlk) is an evolutionarily conserved protein kinase involved
      in Wnt/beta-catenin signalling. However, the roles of NLK in Wnt/beta-catenin
      signalling in vertebrates remain unclear. Here, we show that inhibition of Nlk2
      function in zebrafish results in decreased Lymphoid enhancer factor-1 (Lef1)
      mediated gene expression and cell proliferation in the presumptive midbrain,
      resulting in a reduction of midbrain tectum size. These defects are related to
      phosphorylation of Lef1 by Nlk2. Thus, Nlk2 is essential for the phosphorylation
      and activation of Lef1 transcriptional activity in neural progenitor cells
      (NPCs). In NPC-like mammalian cells, NLK is also required for the phosphorylation
      and activation of LEF1 transcriptional activity. Phosphorylation of LEF1 induces
      its dissociation from histone deacetylase, thereby allowing transcription
      activation. Furthermore, we demonstrate that NLK functions downstream of
      Dishevelled (Dvl) in the Wnt/beta-catenin signalling pathway. Our findings reveal
      a novel role of NLK in the activation of the Wnt/beta-catenin signalling pathway.

PMID- 22373575
TI  - Claudin-14 regulates renal Ca++ transport in response to CaSR signalling via a
      novel microRNA pathway.
AB  - The paracellular claudin channel of the thick ascending limb (TAL) of Henle is
      critical for Ca(++) reabsorption in the kidney. Genome-wide association studies
      (GWASs) have identified claudin-14 associated with hypercalciuric
      nephrolithiasis. Here, we show that claudin-14 promoter activity and transcript
      are exclusively localized in the TAL. Under normal dietary condition, claudin-14
      proteins are suppressed by two microRNA molecules (miR-9 and miR-374). Both
      microRNAs directly target the 3'-UTR of claudin-14 mRNA; induce its mRNA decay
      and translational repression in a synergistic manner. Through physical
      interaction, claudin-14 blocks the paracellular cation channel made of claudin-16
      and -19, critical for Ca(++) reabsorption in the TAL. The transcript and protein
      levels of claudin-14 are upregulated by high Ca(++) diet, while downregulated by
      low Ca(++) diet. Claudin-14 knockout animals develop hypermagnesaemia,
      hypomagnesiuria, and hypocalciuria under high Ca(++) dietary condition. MiR-9 and
      miR-374 transcript levels are regulated by extracellular Ca(++) in a reciprocal
      manner as claudin-14. The Ca(++) sensing receptor (CaSR) acts upstream of the
      microRNA-claudin-14 axis. Together, these data have established a key regulatory
      role for claudin-14 in renal Ca(++) homeostasis.

PMID- 22373576
TI  - Highly diverse TCRalpha chain repertoire of pre-immune CD8+ T cells reveals new
      insights in gene recombination.
AB  - Although the T-cell receptor alphadelta (TCRalphadelta) locus harbours large
      libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to
      previous studies the TCRalpha chain repertoire is of limited diversity due to
      restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By
      sequencing tens of millions of TCRalpha chain transcripts from naive mouse CD8(+)
      T cells, we observed a hugely diverse repertoire, comprising nearly all possible
      TRAV-TRAJ combinations. Our findings are not compatible with sequential
      coordinate gene recombination, but rather with a model in which contraction and
      DNA looping in the TCRalphadelta locus provide equal access to TRAV and TRAJ gene
      segments, similarly to that demonstrated for IgH gene recombination. Generation
      of the observed highly diverse TCRalpha chain repertoire necessitates deletion of
      failed attempts by thymic-positive selection and is essential for the formation
      of highly diverse TCRalphabeta repertoires, capable of providing good protective
      immunity.

PMID- 22373577
TI  - Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced
      53BP1 foci at G1/G2 cell-cycle phases.
AB  - The methyltransferase DOT1L methylates histone H3 at K79 to facilitate specific
      biological events. H3K79 dimethylation (H3K79-2Me) by DOT1L influences the DNA
      damage response by promoting 53BP1 recruitment to DNA damage sites; however, it
      is unclear if this methylation is required as 53BP1 interacts with dimethylated
      H4 (H4K20-2Me) with a much higher affinity. We demonstrate that H3K79-2Me, while
      negligible during S-phase, is required for ionizing radiation (IR)-induced 53BP1
      foci formation during G1/G2-phases when H4K20-2Me levels are low. Further, we
      describe an essential role for HLA-B-associated transcript 3 (Bat3) in regulating
      this process in U2OS cells. Bat3 co-localizes with DOT1L at histone H3, and Bat3
      knockdown results in decreased DOT1L-H3 interaction and H3K79-2Me, leading to a
      reduction in IR-induced 53BP1 foci formation, defects in DNA repair and increased
      sensitivity to IR. We demonstrate that a conserved Bat3 ubiquitin-like motif and
      a conserved DOT1L ubiquitin-interacting motif promote DOT1L-Bat3 interaction to
      facilitate efficient H3K79-2Me and IR-induced 53BP1 foci formation during G1/G2
      phases. Taken together, our findings identify a novel role for Bat3 in regulating
      DOT1L function, which plays a critical role in DNA damage response.

PMID- 22373578
TI  - miR-493 induction during carcinogenesis blocks metastatic settlement of colon
      cancer cells in liver.
AB  - Liver metastasis is a major lethal complication associated with colon cancer, and
      post-intravasation steps of the metastasis are important for its clinical
      intervention. In order to identify inhibitory microRNAs (miRNAs) for these steps,
      we performed 'dropout' screens of a miRNA library in a mouse model of liver
      metastasis. Functional analyses showed that miR-493 and to a lesser extent miR
      493(*) were capable of inhibiting liver metastasis. miR-493 inhibited retention
      of metastasized cells in liver parenchyma and induced their cell death. IGF1R was
      identified as a direct target of miR-493, and its inhibition partially
      phenocopied the anti-metastatic effects. High levels of miR-493 and miR-493(*),
      but not pri-miR-493, in primary colon cancer were inversely related to the
      presence of liver metastasis, and attributed to an increase of miR-493 expression
      during carcinogenesis. We propose that, in a subset of colon cancer, upregulation
      of miR-493 during carcinogenesis prevents liver metastasis via the induction of
      cell death of metastasized cells.

PMID- 22373579
TI  - RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment
      to DNA damage sites.
AB  - In response to DNA damage, cells initiate complex signalling cascades leading to
      growth arrest and DNA repair. The recruitment of 53BP1 to damaged sites requires
      the activation of the ubiquitination cascade controlled by the E3 ubiquitin
      ligases RNF8 and RNF168, and methylation of histone H4 on lysine 20. However,
      molecular events that regulate the accessibility of methylated histones, to allow
      the recruitment of 53BP1 to DNA breaks, are unclear. Here, we show that like
      53BP1, the JMJD2A (also known as KDM4A) tandem tudor domain binds dimethylated
      histone H4K20; however, JMJD2A is degraded by the proteasome following the DNA
      damage in an RNF8-dependent manner. We demonstrate that JMJD2A is ubiquitinated
      by RNF8 and RNF168. Moreover, ectopic expression of JMJD2A abrogates 53BP1
      recruitment to DNA damage sites, indicating a role in antagonizing 53BP1 for
      methylated histone marks. The combined knockdown of JMJD2A and JMJD2B
      significantly rescued the ability of RNF8- and RNF168-deficient cells to form
      53BP1 foci. We propose that the RNF8-dependent degradation of JMJD2A regulates
      DNA repair by controlling the recruitment of 53BP1 at DNA damage sites.

PMID- 22373580
TI  - Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric
      cancer.
AB  - KLK6 encoding kallikrein-related peptidase 6, a trypsin-like serine protease, has
      been shown to be upregulated in several cancers, although the tumorigenic role of
      KLK6 has not been elucidated. In this study, KLK6 was identified as a highly
      upregulated gene in gastric cancer; therefore, the possibility that KLK6 might be
      a suitable candidate tumor marker was examined. RT-PCR and immunohistochemical
      analysis showed overexpression of KLK6 in gastric cancer tissues compared to
      nontumor regions. Sera from gastric cancer patients had a 1.7-fold increase in
      KLK6 (373.1 MUg/L, P = 0.048) compared to healthy individuals (214.2 MUg/L),
      although there was no significant difference among patients with various tumor
      stages. Cellular invasiveness decreased by 45% in cells transfected with KLK6
      specific small interfering RNA. Exogenous overexpression of KLK6 led to decreased
      activity of the E-cadherin promoter. This study shows that KLK6 is significantly
      upregulated and secreted in gastric cancer tissues and sera, suggesting that KLK6
      might be used as a potential biomarker and therapeutic target for gastric cancer.

PMID- 22373582
TI  - Association of polymorphisms in one-carbon metabolizing genes with breast cancer
      risk in Syrian women.
AB  - Dietary folate status as well as polymorphisms in one-carbon metabolism genes may
      affect the risk of breast cancer through aberrant DNA methylation and altered
      nucleotide synthesis and DNA repair. A large number of studies investigated the
      role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase
      reductase (MTRR) polymorphisms in breast cancer with inconsistent results.
      Association between multiple polymorphisms in one-carbon metabolism genes and
      breast cancer was not studied before in an Arab population. The purpose of the
      present study is to test the hypothesis that polymorphisms in one-carbon
      metabolism genes are associated with breast cancer susceptibility in Syrian
      breast cancer women patients. A total of 245 subjects (119 breast cancer women
      patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and
      MTRR A66G polymorphisms. Association was tested for under numerous genetic
      models. A statistically significant association was found for MTHFR A1298C
      polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68,
      95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no
      significant association was found for MTHFR C677T or MTRR A66G under any of the
      genetic models tested. The effects of the compound genotypes were also examined.
      The 66GG genotype was found to be protective against breast cancer when combined
      with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR =
      0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the
      hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk
      for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.

PMID- 22373581
TI  - Targeted therapy in head and neck cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) of multi-factorial etiopathogenesis
      is rising worldwide. Treatment-associated toxicity problems and treatment failure
      in advanced disease stages with conventional therapies have necessitated a focus
      on alternative strategies. Molecular targeted therapy, with the potential for
      increased selectivity and fewer adverse effects, hold promise in the treatment of
      HNSCC. In an attempt to improve outcomes in HNSCC, targeted therapeutic
      strategies have been developed. These strategies are focusing on the molecular
      biology of HNSCC in an attempt to target selected pathways involved in
      carcinogenesis. Inhibiting tumor growth and metastasis by focusing on specific
      protein or signal transduction pathways or by targeting the tumor
      microenvironment or vasculature are some of the new approaches. Targeted agents
      for HNSCC expected to improve the effectiveness of current therapy include EGFR
      inhibitors (Cetuximab, Panitumumab, Zalutumumab), EGFR tyrosine kinase inhibitors
      (Gefitinib, Erloitinib), VEGFR inhibitors (Bevacizumab, Vandetanib), and various
      inhibitors of, e.g., Src-family kinase, PARP, proteasome, mTOR, COX, and heat
      shock protein. Moreover, targeted molecular therapy can also act as a complement
      to other existing cancer therapies. Several studies have demonstrated that the
      combination of targeting techniques with conventional current treatment protocols
      may improve the treatment outcome and disease control, without exacerbating the
      treatment related toxicities. Some of the targeted approaches have been proved as
      promising therapeutic potentials and are already in use, whereas remainder
      exhibits mixed result and necessitates further studies. Identification of
      predictive biomarkers of resistance or sensitivity to these therapies remains a
      fundamental challenge in the optimal selection of patients most likely to benefit
      from targeted treatment.

PMID- 22373583
TI  - Serum HE4 as a diagnostic and prognostic marker for lung cancer.
AB  - We evaluated the diagnostic and prognostic efficacy of human epididymis protein 4
      (HE4) for lung cancer patients by using our novel enzyme-linked immunosorbent
      assay (ELISA) system. We measured serum HE4 levels of cancer patients including
      49 lung cancer and 18 ovarian cancer patients. Furthermore, we evaluated the
      relationship between serum HE4 levels and overall survival after chemotherapy of
      24 lung cancer patients. Serum HE4 levels were significantly higher for non
      small, small cell lung cancer and ovarian cancer patients than for healthy
      controls. The area under the receiver operating characteristic curve (AUC) was
      calculated for differentiation of lung cancer patients and healthy controls. AUC
      for serum HE4 was 0.988 for differentiating lung cancer patients from healthy
      controls, with a cutoff value of 6.56 ng/ml (sensitivity = 89.8%, specificity =
      100%). Serum HE4 levels were elevated in 36/40 (90.0%) non-small cell lung cancer
      patients, 8/9 (88.9%) small cell lung cancer patients and 8/18 (44.4%) ovarian
      cancer patients. High levels of serum HE4 (>15 ng/ml) after chemotherapy were
      significantly correlated with worse overall survival after the treatment. These
      findings suggest that serum HE4 is a potential diagnostic and prognostic marker
      for lung cancer patients.

PMID- 22373584
TI  - The effects of RKIP gene expression on the biological characteristics of human
      triple-negative breast cancer cells in vitro.
AB  - The purpose of this study was to investigate the effect of Raf kinase inhibitor
      protein (RKIP) on the growth, proliferation, invasion and metastasis of triple
      negative breast cancer (TNBC) cells to provide experimental evidence for
      developing future therapies against human TNBC. The pcDNA3.1-RKIP eukaryotic
      expression vector was constructed and transfected into the TNBC cell line MDA-MB
      231. The alterations of the biological characteristics of RKIP-transfected MDA-MB
      231 cells were analyzed using the following approaches: a growth curve, a 3-(4,5
      dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay,
      bromodeoxyuridine (BrdU) staining and a cell migration assay. The effects of the
      RKIP gene on MMP-1 and MMP-2 expression were also examined. The pcDNA3.1 empty
      vector-transfected and mock-transfected MDA-MB-231 cells were used as control
      groups. Compared with the empty vector-transfected and mock-transfected cells,
      the cell growth of RKIP-transfected MDA-MB-231 cells was significantly reduced.
      The empty vector-transfected group was not significantly different compared with
      the mock-transfected MDA-MB-231 cells. The results of the MTT and BrdU assays
      demonstrated that the proliferation of pcDNA3.1-RKIP-transfected cells was
      significantly reduced compared to the control cells (P < 0.05). The result of the
      cell migration assay suggested that the cross-membrane migration rate of the
      pcDNA3.1-RKIP-transfected cells was significantly lower than that of the control
      MDA-MB-231 cells (P < 0.05). We also demonstrated that RKIP may inhibit MMP-1 and
      MMP-2 expression in MDA-MB-231 cells. The RKIP gene may play a role in inhibiting
      cellular proliferation. The RKIP gene may also have some inhibitory effects on
      the invasiveness and metastatic capability of human TNBC cells.

PMID- 22373585
TI  - Alteration of galectin-1 during tumorigenesis of Opisthorchis viverrini infection
      induced cholangiocarcinoma and its correlation with clinicopathology.
AB  - Galectin-1 is a beta-galactoside-binding lectin to function in cell adhesion,
      proliferation, differentiation, and might be involved in tumor progression and
      metastasis. In the present study, the expression kinetics of galectin-1 during
      the tumorigenesis of a parasite Opisthorchis viverrini infection-induced
      cholangiocarcinoma (CCA) was investigated in model animal hamsters, and the
      expression was confirmed in human CCA cases. It was found that galectin-1 was
      overexpressed at mRNA and protein levels with the tumor progression. The mRNA
      expression was elevated in very early stage during tumorigenesis and the increase
      was time dependent. Galectin-1 protein expression profiles indicated that the
      increased expression was mainly located in the epithelium of extensively
      proliferated and hyperplasia small bile ducts at early stage of CCA development
      in model animal and mainly in the extensive tumor stroma tissues in both model
      animals and human CCA cases at later stage. The analysis of correlation of the
      overexpression with clinicopathology in human cases suggested that high
      expression of galectin-1 was associated with advanced stage and metastasis and
      with shorter cumulative overall survival of the patients. Multivariate Cox
      regression analysis revealed that galectin-1 expression was of independent
      prognostic significance for CCA. Our results suggest that galectin-1 is likely
      involved in the tumorigenesis and expected to serve as a tumor stroma marker in
      diagnosis and prediction of metastasis and poor prognosis of the opisthorchiasis
      associated CCA.

PMID- 22373586
TI  - A dual cytotoxic and anti-angiogenic water-soluble gold(III) complex induces
      endoplasmic reticulum damage in HeLa cells.
AB  - The water-soluble gold(III) complex [Au(III)(butyl-C^N)biguanide]Cl (butyl-HC^N =
      2-(4-n-butylphenyl)pyridine, BCN) displays cytotoxicity through S-phase cell
      cycle arrest and endoplasmic reticulum (ER) damage in HeLa cells, and shows a
      promising anti-angiogenic effect at sub-cytotoxic concentrations.

PMID- 22373587
TI  - Transcriptomics and systems biology analysis in identification of specific
      pathways involved in cacao resistance and susceptibility to witches' broom
      disease.
AB  - This study reports on expression analysis associated with molecular systems
      biology of cacao-Moniliophthora perniciosa interaction. Gene expression data were
      obtained for two cacao genotypes (TSH1188, resistant; Catongo, susceptible)
      challenged or not with the fungus M. perniciosa and collected at three time
      points through disease. Using expression analysis, we identified 154 and 227
      genes that are differentially expressed in TSH1188 and Catongo, respectively. The
      expression of some of these genes was confirmed by RT-qPCR. Physical protein
      protein interaction (PPPI) networks of Arabidopsis thaliana orthologous proteins
      corresponding to resistant and susceptible interactions were obtained followed by
      cluster and gene ontology analyses. The integrated analysis of gene expression
      and systems biology allowed designing a general scheme of major mechanisms
      associated with witches' broom disease resistance/susceptibility. In this sense,
      the TSH1188 cultivar shows strong production of ROS and elicitors at the
      beginning of the interaction with M. perniciosa followed by resistance signal
      propagation and ROS detoxification. On the other hand, the Catongo genotype
      displays defense mechanisms that include the synthesis of some defense molecules
      but without success in regards to elimination of the fungus. This phase is
      followed by the activation of protein metabolism which is achieved with the
      production of proteasome associated with autophagy as a precursor mechanism of
      PCD. This work also identifies candidate genes for further functional studies and
      for genetic mapping and marker assisted selection.

PMID- 22373588
TI  - Patient profile in a bone health and osteoporosis prevention service in Ireland.
AB  - OBJECTIVES: To (1) characterise a cohort of patients attending a major
      osteoporosis clinic in Ireland and (2) examine the prescribing of preventative
      therapies amongst these patients. METHODS: Data were taken from 2006-2007 on
      patients attending the Osteoporosis Clinic at St. James's Hospital, Dublin.
      Information gathered included age, gender, fracture history, past medical and
      surgical history, co-morbidities, the results of the first DXA scans, anti
      resorptive therapies along with other medications prescribed. RESULTS: Of all
      patients 87.6% were female and the mean age was 68 years (SD = 14.31). In total
      166 (74%) patients had osteoporosis, 40 (17.8%) had osteopenia and 18 patients
      (8%) had normal T-score values, 163 (72.7%) had a history of a fracture. Only
      13.7% of the patients did not have a documented history of other co-morbidities.
      CONCLUSION: Comprehensive services such as the Osteoporosis Clinic at St. James's
      Hospital can provide the necessary screening, monitoring and prescribing of
      appropriate osteoporosis medications with additional follow-up if required to
      this at risk group reducing the unnecessarily traumatic effects of the disease on
      patients.

PMID- 22373589
TI  - Premedication with intravenous dexmedetomidine-midazolam suppresses fentanyl
      induced cough.
AB  - BACKGROUND: The incidence of fentanyl-induced cough (FIC) occurs frequently
      during induction of general anesthesia, and methods to prevent it are needed. In
      this study, we hypothesized that premedication with intravenous dexmedetomidine
      midazolam can suppress FIC effectively. METHODS: A total of 440 patients of ASA I
      or II, aged 18-65 years, weighing 41-90 kg, undergoing elective surgery were
      randomized into four groups of 110 each, using computer-generated random numbers.
      Group S + S: normal saline 0.15 ml/kg + normal saline 0.06 ml/kg; Group S + M:
      normal saline 0.15 ml/kg + midazolam 0.06 mg/kg; Group D + S: dexmedetomidine 0.6
      MUg/kg + normal saline 0.06 ml/kg; Group D + M: dexmedetomidine 0.6 MUg/kg +
      midazolam 0.06 mg/kg. After receiving the above-mentioned drugs, all patients
      received i.v. fentanyl (3 MUg/kg). After fentanyl administration, the onset time
      and the severity of cough for 1 min were recorded. Severity of coughing was
      graded as mild (1-2), moderate (3-5) and (>5) based on the number of cough per
      minute. RESULTS: Forty-five (40.9%) patients had cough in Group S + S, 70 (63.6%)
      in Group S + M and 25 (22.7%) in Group D + S. None of the patients in Group D + M
      had any cough. The total incidence of cough was significantly higher (P < 0.01)
      in Group S + M in comparison to that in other groups. The onset time of cough was
      significantly shorter in Group S + M (13.8 +/- 3.8 s) than in Group S + S (18.7
      +/- 3.9 s, P < 0.01) or Group D + S. (18.2 +/- 3.2 s, P < 0.01). However, there
      was no significant difference among groups in cough severity. CONCLUSIONS:
      Pretreatment with dexmedetomidine-midazolam could completely suppress FIC caused
      by fentanyl 3 MUg/kg injection within 2 s.

PMID- 22373590
TI  - Cardiomyopathy of Friedreich's ataxia (FRDA).

PMID- 22373591
TI  - Management of children exposed to multidrug-resistant Mycobacterium tuberculosis.
AB  - Children exposed to multidrug-resistant (MDR) Mycobacterium tuberculosis are at
      risk of developing MDR tuberculosis. Where treatment is available, it is lengthy,
      expensive, and associated with poor adherence and notable morbidity and
      mortality. Preventive treatment effectively lowers the risk of disease
      progression for contacts of individuals with drug-susceptible tuberculosis, but
      this strategy is poorly studied for contacts of people with MDR tuberculosis. In
      this Review we discuss the management of child contacts of source cases with MDR
      tuberculosis. We pay particular attention to assessment, existing international
      guidelines, possible preventive treatments, rationales for different management
      strategies, and the interaction with and implications of HIV infection.

PMID- 22373592
TI  - Multidrug-resistant tuberculosis in children can be treated.

PMID- 22373593
TI  - Treatment outcomes for children with multidrug-resistant tuberculosis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Paediatric multidrug-resistant (MDR) tuberculosis is a public health
      challenge of growing concern, accounting for an estimated 15% of all global cases
      of MDR tuberculosis. Clinical management is especially challenging, and
      recommendations are based on restricted evidence. We aimed to assess existing
      evidence for the treatment of MDR tuberculosis in children. METHODS: We did a
      systematic review and meta-analysis of published and unpublished studies
      reporting treatment outcomes for children with MDR tuberculosis. We searched
      PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up
      to Oct 31, 2011. Eligible studies included five or more children (aged <=16
      years) with MDR tuberculosis within a defined treatment cohort. The primary
      outcome was treatment success, defined as a composite of cure and treatment
      completion. RESULTS: We identified eight studies, which reported treatment
      outcomes for a total of 315 patients. We recorded much variation in the
      characteristics of patients and programmes. Time to appropriate treatment varied
      from 2 days to 46 months. Average duration of treatment ranged from 6 months to
      34 months, and duration of follow-up ranged from 12 months to 37 months. The
      pooled estimate for treatment success was 81.67% (95% CI 72.54-90.80). Across all
      studies, 5.9% (95% CI 1.3-10.5) died, 6.2% (2.3-10.2) defaulted, and 39.1% (28.7
      49.4) had an adverse event. The most common drug-related adverse events were
      nausea and vomiting. Other serious adverse events were hearing loss, psychiatric
      effects, and hypothyroidism. INTERPRETATION: The treatment of paediatric MDR
      tuberculosis has been neglected, but when children are treated outcomes can be
      achieved that are at least as good as those reported for adults. Programmes
      should be encouraged to report outcomes in children to improve the knowledge base
      for care, especially as new drugs become available. FUNDING: None.

PMID- 22373594
TI  - Severe loss and recovery of vision after glaucoma filtration surgery.
AB  - PURPOSE: To report a case of sudden, severe, unexplained, bilateral loss of
      vision after glaucoma filtration surgery in both eyes; the vision returned 2
      months later. METHODS: The clinical records of the patient were reviewed
      retrospectively. Observations were made and collated as the case progressed.
      RESULTS: A 25-year-old man previously diagnosed with poorly controlled, far
      advanced, juvenile-onset primary open-angle glaucoma underwent bilateral guarded
      filtration procedures. Preoperative visual acuity was 20/40 in the right eye and
      20/100 in the left eye. After the procedure visual acuity was severely diminished
      to no light perception in the right eye and light perception in the left eye.
      There was no apparent cause for the visual reduction other than the decrease in
      intraocular pressure caused by the surgery. Two months postoperatively, the
      patient had visual acuity of 20/80 in the right eye and 20/200 in the left eye.
      Ten months postoperatively, visual acuity was 20/70 in the right eye and 20/200
      in the left eye. Twenty-three months postoperatively, visual acuity was 20/100 in
      the right eye and 20/200 in the left eye. CONCLUSIONS: This case provides
      evidence for the potential reversibility of severe visual loss after glaucoma
      filtration surgery.

PMID- 22373595
TI  - Practice preferences for glaucoma drainage device implantation and
      cyclodestruction in Australia and New Zealand.
AB  - PURPOSE: To evaluate the practice patterns in the use of glaucoma drainage
      devices (GDD) and cyclodestruction among consultant ophthalmologists in Australia
      and New Zealand. MATERIALS AND METHODS: A 22-part questionnaire regarding GDD
      implantation and cyclodestruction practices was sent to all ophthalmologists
      registered with the Royal Australian and New Zealand College of Ophthalmologists
      in 2008 by post or e-mail. RESULTS: Sixty-six percent of 872 questionnaires were
      returned, of these, 14% were from glaucoma subspecialists. Ten percent of all
      respondents performed GDD implantations. Molteno drains were the most popular
      device (69%). The most commonly recognized indications for GDD implantation were
      a history of 2 failed trabeculectomies (85%), neovascular glaucoma (71%),
      iridocorneal endothelial syndrome (55%), and uveitic glaucoma (52%). Only a
      minority of surgeons used intraoperative mitomycin C (38%) or 5-fluorouracil
      (26%) when implanting GDD. Cyclodestruction had been performed by 20% of all
      respondents. External diode cyclophotocoagulation was the most preferred
      treatment mode (73%). Sixty-seven percent treated 180 degrees of the ciliary body
      during initial treatment. Fifty-five percent treated only the earlier untreated
      area during retreatment. Only 11% of surgeons who performed cyclodestruction
      agreed that the indications for cyclodestruction are expanding. CONCLUSIONS: A
      wide range of practice patterns for GDD implantation and cyclodestruction exist
      among Australian and New Zealand ophthalmologists. This likely reflects a paucity
      of good evidence to guide practice. The Australasian indications for GDD
      implantation were moderately different from the reported practice in America.
      Well-designed clinical trials are needed to better define the indications and
      best practice for these 2 important glaucoma treatment modalities.

PMID- 22373596
TI  - Radical innate regulation of autoimmune diabetes.

PMID- 22373597
TI  - Two novel mutations and a previously unreported intronic polymorphism in the
      NOTCH3 gene.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a hereditary disease of small vessel caused by
      mutations in the NOTCH3 gene (NCBI Gene ID: 4854) located on chromosome 19p13.1.
      NOTCH3 consists of 33 exons which encode a protein of 2321 amino acids. Exons 3
      and 4 were found to be mutation hotspots, containing more than 65% of all CADASIL
      mutations. We performed direct sequencing on an ABI 3130 Genetic Analyser to
      screen for mutations and polymorphisms on 300 patients who were clinically
      suspected to have CADASIL. First, exons 3 and 4 were screened in NOTCH3 and if
      there were no variations found, then extended CADASIL testing (exons 2, 11, 18
      and 19) was offered to patients. Here we report two novel non-synonymous
      mutations identified in the NOTCH3 gene. The first mutation, located in exon 4
      was found in a 49-year-old female and causes an alanine to valine amino acid
      change at position 202 (605C>T). The second mutation, located in exon 11, was
      found in a 66-year-old female and causes a cysteine to arginine amino acid change
      at position 579 (1735T>C). We also report a 46-year-old male with a known
      polymorphism Thr101Thr (rs3815188) and an unreported polymorphism
      NM_000435.2:c.679+60G>A observed in intron 4 of the NOTCH3 gene. Although
      Ala202Ala (rs1043994) is a common polymorphism in the NOTCH3 gene, our reported
      novel mutation (Ala202Val) causes an amino acid change at the same locus. Our
      other reported mutation (Cys579Arg) correlates well with other known mutations in
      NOTCH3, as the majority of the CADASIL-associated mutations in NOTCH3 generally
      occur in the EGF-like (epidermal growth factor-like) repeat domain, causing a
      change in the number of cysteine residues. The intronic polymorphism
      NM_000435.2:c.679+60G>A lies close to the intron-exon boundary and may affect the
      splicing mechanism in the NOTCH3 gene.

PMID- 22373598
TI  - Pioglitazone in clinical practice: where are we now?
AB  - Pioglitazone, a thiazolidinedione, improves insulin sensitivity and thus reduces
      blood glucose. Clinical trials have suggested potential cardiovascular outcome
      benefits in association with pioglitazone; however, safety concerns are mounting,
      with recent data suggesting a link between pioglitazone and an increased risk of
      bladder cancer. There is thus a growing focus on the risk-benefit profile of this
      agent and hence its potential role in the blood glucose-lowering treatment
      algorithm for people with type 2 diabetes. There are clear potential outcome
      benefits associated with pioglitazone. In this review, the authors focus on
      putting the true risk-benefit profile of pioglitazone into context based on
      critical appraisal of the currently available evidence.

PMID- 22373599
TI  - An oral cancer biobank initiative: a platform for multidisciplinary research in a
      developing country.
AB  - Identification of diagnostic markers for early detection and development of novel
      and therapeutic agents for effective patient management are the main motivation
      for cancer research. Biological specimens from large cohort and case-control
      studies which are crucial in providing successful research outcomes are often the
      limiting factor that hinders research efforts, especially in developing
      countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System
      (MOCDTBS) were established to systematically collect large number of samples with
      comprehensive sociodemographic, clinicopathological, management strategies,
      quality of life and associated patient follow-up data to facilitate oral cancer
      research in Malaysia. The MOCDTBS also promotes sharing among researchers and the
      development of a multidisciplinary research team. The following article aims to
      describe the process of setting-up and managing the MOCDTBS.

PMID- 22373600
TI  - Wavefunction-based electron correlation methods for solids.
AB  - In this article we provide an overview of the most common ways of treating
      electron correlation effects in 3D-periodic systems with some emphasize on
      wavefunction-based correlation methods such as the method of increments and the
      local MP2 method implemented in the Cryscor program. We discuss strengths and
      weaknesses of the different approaches and give examples for their application.
      Additionally, for the method of increments we discuss recent developments for its
      application to open shell systems and problems related to the treatment of
      graphene sheets.

PMID- 22373601
TI  - Differential release of high mannose structural isoforms by fungal and bacterial
      endo-beta-N-acetylglucosaminidases.
AB  - Endo-beta-N-acetylglucosaminidases (ENGases) are widely used to remove N-linked
      oligosaccharides from glycoproteins for glycomic and proteomic studies and
      biopharmaceutical processes. Although several ENGases are widely available and
      their main oligosaccharide structural preferences are generally known (i.e. high
      mannose, hybrid or complex), the preferences of ENGases from different kingdoms
      for individual structural isoforms within the major classes of N-linked
      oligosaccharides have previously not been compared. In this work, a fungal ENGase
      (Endo Tv) was purified for the first time from a commercial Trichoderma viride
      chitinase mixture by sequential anion exchange and size exclusion chromatography,
      a commonly used strategy for purification of chitinases and endo enzymes.
      Oligosaccharides released from substrate glycoproteins by Endo Tv were identified
      and quantified by high pH anion exchange chromatography with pulsed amperometric
      detection and verified by mass spectrometric analysis. Unlike the widely-used
      bacterial ENGases, Endo H and Endo F1, Endo Tv released exclusively high mannose
      N-linked oligosaccharides from RNase B, ovalbumin, and yeast invertase. Endo Tv
      did not hydrolyze fucosylated, hybrid, complex type or bisecting N
      acetylglucosamine-containing structures from bovine fetuin, ovalbumin and IgG.
      When compared to the bacterial ENGase, Endo H, the relative ratio of high-mannose
      oligosaccharide structural isoforms released from RNase B by Endo Tv was found to
      differ, with Endo Tv releasing more Man5GlcNAc and Man7GlcNAc isoform I and less
      Man(9)GlcNAc from RNase B. Based on these data, it is suggested that use of
      ENGases from multiple sources may serve to balance an introduced bias in
      quantitative analysis of released structural isoforms and may further prove
      valuable in biochemical structure-function studies.

PMID- 22373602
TI  - Separation of chiral molecules: a way to homochirality.
AB  - A mechanism for separating chiral molecules is proposed. The separation of two
      enantiomers in an aquifer is considered. The molecules are dragged in the aquifer
      porous medium by a flow of water or of another liquid. The molecule velocity is
      u=v/R, where v is the liquid velocity, and R is the retardation factor. The
      aquifer consists of two one-dimensional layers disposed in series. The layers
      differ by the retardation factor or by the liquid velocity. The enantiomer
      velocity is a function of the enantiomer concentrations. This function is
      different in the two layers. For certain values of the model parameters and when
      the molecules entering the aquifer are enantiomerically enriched or when the
      medium is chiral, the concentration of one enantiomer increases around the
      interface between the two layers and in one layer, whereas the concentration of
      the other enantiomer decreases. Enantiomer synthesis and decay are not taken into
      account. The needed values of the parameters can be obtained when the enantiomers
      are moved by an alternating liquid flow, and the retardation factor oscillates in
      synchronism with the alternating liquid flow. The parameters of the model are
      then understood as quantities averaged over one oscillation period. The equations
      that give the values of the stationary concentrations of the enantiomers are
      found. The evolution of the enantiomer concentrations is determined by
      numerically solving a system of two nonlinear advection-dispersion equations. The
      proposed mechanism may have played a role in the emergence of biomolecular
      homochirality.

PMID- 22373603
TI  - Oligomerization of glycine and alanine catalyzed by iron oxides: implications for
      prebiotic chemistry.
AB  - Iron oxide minerals are probable constituents of the sediments present in
      geothermal regions of the primitive earth. They might have adsorbed different
      organic monomers (amino acids, nucleotides etc.) and catalyzed polymerization
      processes leading to the formation of the first living cell. In the present work
      we tested the catalytic activity of three forms of iron oxides (Goethite,
      Akaganeite and Hematite) in the intermolecular condensation of each of the amino
      acids glycine and L-alanine. The effect of zinc oxide and titanium dioxide on the
      oligomerization has also been studied. Oligomerization studies were performed for
      35 days at three different temperatures 50, 90 and 120 degrees C without applying
      drying/wetting cycling. The products formed were characterized by HPLC and ESI-MS
      techniques. All three forms of iron oxides catalyzed peptide bond formation
      (23.2% of gly2 and 10.65% of ala2). The reaction was monitored every 7 days.
      Formation of peptides was observed to start after 7 days at 50 degrees C. Maximum
      yield of peptides was found after 35 days at 90 degrees C. Reaction at 120
      degrees C favors formation of diketopiperazine derivatives. It is also important
      to note that after 35 days of reaction, goethite produced dimer and trimer with
      the highest yield among the oxides tested. We suggest that the activity of
      goethite could probably be due to its high surface area and surface acidity.

PMID- 22373604
TI  - Hypothesis: origin of life in deep-reaching tectonic faults.
AB  - The worldwide discussion on the origin of life encounters difficulties when it
      comes to estimate the conditions of the early earth and to define plausible
      environments for the development of the first complex organic molecules. Until
      now, the role of the earth's crust has been more or less ignored. In our opinion,
      deep-reaching open, interconnected tectonic fault systems may provide possible
      reaction habitats ranging from nano- to centimetre and even larger dimensions for
      the formation of prebiotic molecules. In addition to the presence of all
      necessary raw materials including phosphate, as well as variable pressure and
      temperature conditions, we suggest that supercritical CO2 as a nonpolar solvent
      could have played an important role. A hypothetical model for the origin of life
      is proposed which will be used to design crucial experiments for the model's
      verification. Because all proposed processes could still occur in tectonic faults
      at the present time, it may be possible to detect and analyse the formation of
      prebiotic molecules in order to assess the validity of the proposed hypothesis.

PMID- 22373605
TI  - Potent combination therapy for human breast tumors with high doses of 5
      fluorouracil: remission and lack of host toxicity.
AB  - PURPOSE: The purpose of this investigation was to evaluate the effectiveness of
      oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host
      toxicity and enhancing its chemotherapeutic efficacy against human breast tumors.
      PTAU is a potent and specific inhibitor of uridine phosphorylase (UP, EC
      2.4.2.3), the enzyme responsible for uridine catabolism. METHODS: SCID mice
      bearing MDA-MB-468 and MCF-7 human breast tumors were injected intraperitoneally
      with FUra (50, 200 or 300 mg/kg) on days 17, 24, and 31 after tumor cell
      inoculation. PTAU (120 mg/kg), uridine (1,320 mg/kg), or their combination was
      administered orally two or 4 h after FUra injection. Another four administrations
      of PTAU plus uridine were given every 8 h after the first treatment with PTAU
      plus uridine. Survival and body weight were used to evaluate host toxicity. Tumor
      weight was used to evaluate the efficacy of the drugs on tumor growth. The mice
      were monitored for 38 days. RESULTS: Administration of the maximum tolerated dose
      (50 mg/kg) of 5-fluorouracil (FUra) to SCID mice bearing human breast MDA-MB-468
      and MCF-7 adenocarcinoma tumor xenografts reduced tumor weight by 59 and 61%,
      respectively. Administration of 200 mg/kg FUra resulted in 100% mortality. Oral
      administration of uridine (1,320 mg/kg) alone, 2 h following the administration
      of 200 mg/kg FUra, did not rescue from FUra host toxicity as all the mice died.
      Administration of 120 mg/kg PTAU resulted in partial rescue from this lethal dose
      of FUra as 38% of inoculated mice survived and the tumor weights were reduced by
      approximately 67%. Coadministration of PTAU plus uridine resulted in complete
      rescue from the toxicity of FUra. All of the mice survived, and MDA-MB-468 and
      MCF-7 tumor weights were reduced by 97% and total remission, respectively.
      Doubling the FUra treatment dose to 400 mg/kg in the MDA-MB-468 inoculated mice,
      with the administration of the adjuvant combination treatment of PTAU plus
      uridine, was unsuccessful in rescuing from FUra toxicity as all the mice died.
      Lowering the dose of FUra to 300 mg/kg, under the same conditions, resulted in
      67% mice survival, and the MCF-7 tumor weights were reduced by 100%. Treatment
      with uridine alone did not protect from FUra toxicity at 200, 300, and 400 mg/kg
      as all of the mice died. At the higher dose of 300 and 400 mg/kg FUra, PTAU alone
      had no rescuing effect. There was no significant difference between MDA-MB-468
      and MCF-7 in their response to the different regimens employed in this study in
      spite of the fact that MDA-MB-468 is estrogen receptor negative while MCF-7 is
      estrogen receptor positive. CONCLUSIONS: The present results demonstrate that the
      combination of PTAU plus uridine represents an exceptionally efficient method in
      increasing FUra chemotherapeutic efficacy while minimizing its host toxicity. The
      efficiency of the PTAU plus uridine combination can be attributed to the
      extraordinary effectiveness of this combination treatment in raising and
      maintaining higher levels of uridine in vivo (Al Safarjalani et al. in Cancer
      Chemo Pharmacol 55:541-551, 2005). Therefore, the combination of PTAU plus
      uridine can provide a better substitute for the massive doses of uridine
      necessary to rescue or protect from FUra host-toxicities, without the toxic side
      effects associated with such doses of uridine. The combination may also allow the
      escalation of FUra doses for better chemotherapeutic efficacy against human
      breast carcinoma, with the possibility of avoiding FUra host-toxicities.
      Alternatively, the combination of PTAU and uridine may be useful as an antidote
      in the few cases when cancer patients receive a lethal overdose of FUra.

PMID- 22373606
TI  - Can we improve interprofessional team-based patient care without calling 9-1-1?

PMID- 22373607
TI  - More about the causes and consequences of the expanding medical student debt.

PMID- 22373609
TI  - More about technology-enhanced learning in medical education.

PMID- 22373611
TI  - Another reason why primary care for the elderly is so important.

PMID- 22373612
TI  - Foreign language assessment and training in U.S. medical education is a must.

PMID- 22373613
TI  - Journal clubs:  what not to do.

PMID- 22373614
TI  - Commentary: Sense and sensibility: the role of specialists in health care reform.
AB  - How to redesign the incentives structure in the United States to reward effective
      coordinated care rather than production volume is a staggering public health
      policy challenge. In the mind of the public, there is a fine distinction between
      health care rationing and rational health care. Specialists have a vital but
      underappreciated role in reining in health care costs, but specific incentives to
      elicit behavior change with positive social outcomes remain ambiguous. It is
      imperative, therefore, that redesigning the incentives structure is thoughtfully
      considered, modeled, and tested prior to implementation, lest an inferior-quality
      model is inadvertently adopted and costs are only marginally contained. Quality
      metrics need to be universal and reflect real patient outcomes instead of the
      degree of investment by the institution in the reporting tools. Still,
      specialists should take immediate action to implement safe and efficient
      procedures and to assess their long-term impact on patients' quality of life.
      Scientific evaluations should guide both the assessment of the appropriateness
      and the safe delivery of care. Investment in high-quality data architecture and
      the science of health delivery implementation is an imperative if health care
      reform is to achieve its goals. Coordination and collaboration between
      specialists and primary care physicians is essential to this enterprise.
      Specialists can champion these efforts as they pertain to their areas of
      expertise by considering their care episodes in the context of the patient as a
      whole, working closely with generalists, and returning to the mindset of the
      specialist as a family doctor.

PMID- 22373615
TI  - Perspective: Upcoming paradigm shifts for psychiatry in clinical care, research,
      and education.
AB  - Psychiatry is facing a crisis fueled by a fragmented and inefficient system of
      care delivery and a disconnection between the state of research and the state of
      psychiatry education and practice. Many factors contribute to the current state
      of psychiatric care. Psychiatry is a shortage specialty, and this will become
      worse in the near future. In addition, financial pressures have led to decreases
      in psychiatric inpatient and outpatient services and to shorter lengths of
      hospitalization for even the sickest patients. This has resulted in fragmented
      care and an overreliance on polypharmacy. To reach the large number of patients
      needing psychiatric services, health care systems must change and take advantage
      of collaborative and integrative care models and new technologies. Psychiatrists
      must learn to partner more effectively with primary care providers to extend
      their expertise to the greatest number of patients. Currently, psychiatric
      diagnosis is based on a criteria-based system that was developed in the 1970s.
      Advances in systems and molecular neuroscience are beginning to elucidate
      specific brain systems that are dysfunctional in psychiatric illness. This has
      the potential to revolutionize psychiatric diagnosis and treatment in the future.
      However, psychiatry has not yet been successful in incorporating the language of
      this research into clinically meaningful terminology. If neuroscientific progress
      is to be translated into clinical advances, this must change. Residency programs
      must better prepare their graduates to keep up with a psychiatry literature that
      will increasingly use the language of neural circuits to describe psychiatric
      symptomatology and treatments.

PMID- 22373616
TI  - Perspective: Transforming science into medicine: how clinician-scientists can
      build bridges across research's "valley of death".
AB  - Significant increases in National Institutes of Health (NIH) spending on medical
      research have not produced corresponding increases in new treatments and cures.
      Instead, laboratory discoveries remain in what has been termed the "valley of
      death," the gap between bench research and clinical application. Recently, there
      has been considerable discussion in the literature and scientific community about
      the causes of this phenomenon and how to bridge the abyss. In this article, the
      authors examine one possible explanation: Clinician-scientists' declining role in
      the medical research enterprise has had a dilatory effect on the successful
      translation of laboratory breakthroughs into new clinical applications. In recent
      decades, the percentage of MDs receiving NIH funding has drastically decreased
      compared with PhDs. The growing gap between the research and clinical enterprises
      has resulted in fewer scientists with a true understanding of clinical problems
      as well as scientists who are unable to or uninterested in gleaning new basic
      research hypotheses from failed clinical trials. The NIH and many U.S. medical
      schools have recognized the decline of the clinician-scientist as a major problem
      and adopted innovative programs to reverse the trend. However, more radical
      action may be required, including major changes to the NIH peer-review process,
      greater funding for translational research, and significantly more resources for
      the training, debt relief, and early career support of potential clinician
      scientists. Such improvements are required for clinician-scientists to conduct
      translational research that bridges the valley of death and transforms biomedical
      research discoveries into tangible clinical treatments and technologies.

PMID- 22373618
TI  - A roadmap for academic health centers to establish good laboratory practice
      compliant infrastructure.
AB  - Prior to human clinical trials, nonclinical safety and toxicology studies are
      required to demonstrate that a new product appears safe for human testing; these
      nonclinical studies are governed by good laboratory practice (GLP) regulations.
      As academic health centers (AHCs) embrace the charge to increase the translation
      of basic science research into clinical discoveries, researchers at these
      institutions increasingly will be conducting GLP-regulated nonclinical studies.
      Because the consequences for noncompliance are severe and many AHC researchers
      are unfamiliar with Food and Drug Administration regulations, the authors
      describe the regulatory requirements for conducting GLP research, including the
      strict documentation requirements, the necessary personnel training, the
      importance of study monitoring, and the critical role that compliance oversight
      plays in the process. They then explain the process that AHCs interested in
      conducting GLP studies should take before the start of their research program,
      including conducting a needs assessment and a gap analysis and selecting a model
      for GLP compliance. Finally, the authors identify and analyze several critical
      barriers to developing and implementing a GLP-compliant infrastructure at an AHC.
      Despite these challenges, the capacity to perform such research will help AHCs to
      build and maintain competitive research programs and to facilitate the successful
      translation of faculty-initiated research from nonclinical studies to first-in
      human clinical trials.

PMID- 22373617
TI  - A framework for training health professionals in implementation and dissemination
      science.
AB  - The authors describe a conceptual framework for implementation and dissemination
      science (IDS) and propose competencies for IDS training. Their framework is
      designed to facilitate the application of theories and methods from the distinct
      domains of clinical disciplines (e.g., medicine, public health), population
      sciences (e.g., biostatistics, epidemiology), and translational disciplines
      (e.g., social and behavioral sciences, business administration education). They
      explore three principles that guided the development of their conceptual
      framework: Behavior change among organizations and/or individuals (providers,
      patients) is inherent in the translation process; engagement of stakeholder
      organizations, health care delivery systems, and individuals is imperative to
      achieve effective translation and sustained improvements; and IDS research is
      iterative, benefiting from cycles and collaborative, bidirectional relationships.
      The authors propose seven domains for IDS training-team science, context
      identification, literature identification and assessment, community engagement,
      intervention design and research implementation, evaluation of effect of
      translational activity, behavioral change communication strategies-and define 12
      IDS training competencies within these domains. As a model, they describe
      specific courses introduced at the University of California, San Francisco, which
      they designed to develop these competencies. The authors encourage other training
      programs and institutions to use or adapt the design principles, conceptual
      framework, and proposed competencies to evaluate their current IDS training needs
      and to support new program development.

PMID- 22373619
TI  - Aligning the goals of community-engaged research:  why and how academic health
      centers can successfully engage with communities to improve health.
AB  - Community engagement (CE) and community-engaged research (CEnR) are increasingly
      viewed as the keystone to translational medicine and improving the health of the
      nation. In this article, the authors seek to assist academic health centers
      (AHCs) in learning how to better engage with their communities and build a CEnR
      agenda by suggesting five steps: defining community and identifying partners,
      learning the etiquette of CE, building a sustainable network of CEnR researchers,
      recognizing that CEnR will require the development of new methodologies, and
      improving translation and dissemination plans. Health disparities that lead to
      uneven access to and quality of care as well as high costs will persist without a
      CEnR agenda that finds answers to both medical and public health questions. One
      of the biggest barriers toward a national CEnR agenda, however, are the
      historical structures and processes of an AHC-including the complexities of how
      institutional review boards operate, accounting practices and indirect funding
      policies, and tenure and promotion paths. Changing institutional culture starts
      with the leadership and commitment of top decision makers in an institution. By
      aligning the motivations and goals of their researchers, clinicians, and
      community members into a vision of a healthier population, AHC leadership will
      not just improve their own institutions but also improve the health of the nation
      starting with improving the health of their local communities, one community at a
      time.

PMID- 22373620
TI  - Perspective: Guidelines for reporting team-based learning activities in the
      medical and health sciences education literature.
AB  - Medical and health sciences educators are increasingly employing team-based
      learning (TBL) in their teaching activities. TBL is a comprehensive strategy for
      developing and using self-managed learning teams that has created a fertile area
      for medical education scholarship. However, because this method can be
      implemented in a variety of ways, published reports about TBL may be difficult to
      understand, critique, replicate, or compare unless authors fully describe their
      interventions.The authors of this article offer a conceptual model and propose a
      set of guidelines for standardizing the way that the results of TBL
      implementations are reported and critiqued. They identify and articulate the
      seven core design elements that underlie the TBL method and relate them to
      educational principles that maximize student engagement and learning within
      teams. The guidelines underscore important principles relevant to many forms of
      small-group learning. The authors suggest that following these guidelines when
      writing articles about TBL implementations should help standardize descriptive
      information in the medical and health sciences education literature about the
      essential aspects of TBL activities and allow authors and reviewers to
      successfully replicate TBL implementations and draw meaningful conclusions about
      observed outcomes.

PMID- 22373621
TI  - Effecting curricular change through comprehensive course assessment:  using
      structure and process to change outcomes.
AB  - Effective curriculum oversight requires periodic assessment and continuous
      improvement of individual course offerings as well as their overall integration.
      The literature indicates that most course review processes do not use the breadth
      of information available or sufficiently encourage faculty feedback and
      reflection, limiting the value derived. Suggestions for which data to include in
      the course evaluations are available in the literature; however, there is little
      guidance on effective course review structures and processes. In this article,
      the authors discuss a course review process revised as part of a comprehensive
      reform of the George Washington University School of Medicine and Health Sciences
      undergraduate medical school curriculum management structure. The process
      improvements incorporated evaluation practices grounded in the medical and higher
      education literatures and included changes to the data reviewed as well as the
      review timing, participants, and structure. The revised process uses a broad
      array of information, requires significant faculty participation, and uses
      questioning, writing, and dialogue to encourage faculty reflection and learning.
      Course directors indicate that the process helps them focus, and the information
      and the perspectives of others lead to reflection and new ideas. Through the
      process, course directors have changed course content and teaching methods,
      improved assessments of learning, and expanded course integration across the
      curriculum. The procedural and content elements of the process can be easily
      transferred to other medical schools and are applicable to other curricular
      reform projects across the continuum of medical education.

PMID- 22373623
TI  - The significant impact of a competency-based preparatory course for senior
      medical students entering surgical residency.
AB  - PURPOSE: Previous data suggest that formal, structured preparation might improve
      knowledge and skills of senior medical students (SMSs) as they transition to
      surgical residency. However, subsequent impact on clinical performance has not
      been demonstrated. METHOD: The authors developed a comprehensive course for SMSs
      entering surgical residencies and studied the impact of the course on the
      subsequent performance of 2010 graduates (n = 22) compared with matched peers (16
      nonparticipant controls at authors' home institution and 24 nonparticipant peer
      controls at outside institutions; total n = 62). Through pre- and postcourse
      surveys, knowledge tests, and technical examinations, they measured confidence
      and skill acquisition in 32 specific, job-related tasks. They followed
      participants and matched peers into internship and collected performance
      evaluations from supervising senior residents to determine whether course
      graduates would display performance advantages in these same tasks. The authors
      used t tests for all comparisons, alpha = 0.05. RESULTS: Participants
      demonstrated marked improvement in task-specific confidence in all 32 tasks from
      course beginning to end, with improved scores on written and technical skill
      examinations. Further, course participants outperformed peers in all 32 tasks in
      July, with their performance advantage predictably dissipating into the third
      month of residency. There was a marked correlation between confidence and
      competence in all tasks. CONCLUSIONS: Competency-based preparation for surgical
      internship resulted in objective gains in task-specific confidence and test
      performance at course conclusion, translating to improved performance and better
      patient care upon residency matriculation. These data emphasize the significant
      impact of formally preparing SMSs before graduation.

PMID- 22373624
TI  - Teaching and learning moments: Teaching both illness and disease.

PMID- 22373625
TI  - The suicide prevention and depression awareness program at the University of
      California, San Diego School of Medicine.
AB  - To address physician depression and suicide at one U.S. medical school, a faculty
      committee launched a Suicide Prevention and Depression Awareness Program in 2009
      whose focus is medical students', residents', and faculty physicians' mental
      health. The program consists of a two-pronged approach: (1) screening,
      assessment, and referral and (2) education. The screening process is anonymous,
      confidential, and Web based, using customized software created by the American
      Foundation for Suicide Prevention. The educational component consists of a
      medical-school-wide campaign including Grand Rounds on physician burnout,
      depression, and suicide as well as similar sessions geared toward trainees. The
      authors document the process of developing and implementing the program,
      including the program's origins and goals, their critical decision-making
      processes, and successes and challenges of the program's first year.Of the 2,860
      medical students, housestaff, and faculty who received the e-mail invitation in
      the first year, 374 individuals (13%) completed screens, 101/374 (27%) met
      criteria for significant risk for depression or suicide, and 48/374 (13%)
      received referrals for mental health evaluation and treatment. The program
      provided 29 Grand Rounds and other presentations during the first year.This may
      be the first program that aims to increase awareness of depression and to
      destigmatize help-seeking in order to prevent suicide and whose target population
      includes the full panoply of medical school constituents: students, residents,
      and faculty physicians. The program was well received in its first year, and
      while demonstrating the prevention of suicides is difficult, the authors are
      encouraged by the program's results thus far.

PMID- 22373626
TI  - A comparison between physicians and demographically similar peers in accessing
      personal health care.
AB  - PURPOSE: Residents are a unique subpopulation of physicians, training in a
      complex work and educational environment that may create barriers to accessing
      preventive and illness-related health care. This study was designed to
      investigate residents' utilization of personal health care services and compare
      with those of demographically similar peers. METHOD: All 675 residents in a
      large, urban, tertiary care U.S. academic medical center were invited to
      participate in a confidential, Web-based, cross-sectional survey in January 2008.
      Survey responses to questions addressing personal health care were compared with
      those of a demographically similar group using the 2008 survey from the
      Behavioral Risk Factor Surveillance System (BRFSS). The final weights in BRFSS
      were used for a post hoc stratified adjustment in analysis. Logistic regression
      was employed to compare subgroups. RESULTS: Sixty-six percent of residents
      completed the survey. A significantly lower percentage of residents reported
      having a primary care provider (44%) or dentist (65%) or having routine health
      and dental care visits (39% and 53%, respectively) within the past year than
      those in the demographically similar group of 2008 BRFSS. In that group, 83%
      reported having a primary care provider, and 63% and 79% reported having routine
      primary and dental health care visits, respectively. CONCLUSIONS: The residents
      were significantly less likely than demographically similar peers to have a
      primary care provider or dentist or to participate in routine health maintenance.
      Further research into barriers preventing residents from accessing health care,
      and opportunities to address them, is needed.

PMID- 22373627
TI  - Teaching and learning moments: A negotiation between death and learning.

PMID- 22373628
TI  - Medicine and the arts. The doctor by Luke Fildes. Commentary.

PMID- 22373629
TI  - Perspective: Medical education in medical ethics and humanities as the foundation
      for developing medical professionalism.
AB  - Medical education accreditation organizations require medical ethics and
      humanities education to develop professionalism in medical learners, yet there
      has never been a comprehensive critical appraisal of medical education in ethics
      and humanities. The Project to Rebalance and Integrate Medical Education (PRIME)
      I Workshop, convened in May 2010, undertook the first critical appraisal of the
      definitions, goals, and objectives of medical ethics and humanities teaching. The
      authors describe assembling a national expert panel of educators representing the
      disciplines of ethics, history, literature, and the visual arts. This panel was
      tasked with describing the major pedagogical goals of art, ethics, history, and
      literature in medical education, how these disciplines should be integrated with
      one another in medical education, and how they could be best integrated into
      undergraduate and graduate medical education. The authors present the
      recommendations resulting from the PRIME I discussion, centered on three main
      themes. The major goal of medical education in ethics and humanities is to
      promote humanistic skills and professional conduct in physicians. Patient
      centered skills enable learners to become medical professionals, whereas critical
      thinking skills assist learners to critically appraise the concept and
      implementation of medical professionalism. Implementation of a comprehensive
      medical ethics and humanities curriculum in medical school and residency requires
      clear direction and academic support and should be based on clear goals and
      objectives that can be reliably assessed. The PRIME expert panel concurred that
      medical ethics and humanities education is essential for professional development
      in medicine.

PMID- 22373630
TI  - At the membranes of care:  stories in narrative medicine.
AB  - Recognizing clinical medicine as a narrative undertaking fortified by learnable
      skills in understanding stories has helped doctors and teachers to face otherwise
      vexing problems in medical practice and education in the areas of
      professionalism, medical interviewing, reflective practice, patient-centered
      care, and self-awareness. The emerging practices of narrative medicine give
      clinicians fresh methods with which to make contact with patients and to come to
      understand their points of view. This essay provides a brief review of narrative
      theory regarding the structure of stories, suggesting that clinical texts contain
      and can reveal information in excess of their plots. Through close reading of the
      form and content of two clinical texts-an excerpt from a medical chart and a
      portion of an audiotaped interview with a medical student-and a reflection on a
      short section of a modernist novel, the author suggests ways to expand
      conventional medical routines of recognizing the meanings of patients'
      situations. The contributions of close reading and reflective writing to clinical
      practice may occur by increasing the capacities to perceive and then to represent
      the perceived, thereby making available to a writer that which otherwise might
      remain out of awareness. A clinical case is given to exemplify the consequences
      in practice of adopting the methods of narrative medicine. A metaphor of the
      activated cellular membrane is proposed as a figure for the effective
      clinician/patient contact.

PMID- 22373631
TI  - Perspective: Hospital support for anesthesiology departments: aligning incentives
      and improving productivity.
AB  - Anesthesiology groups, particularly academic departments, are increasingly
      dependent on hospital support for financial viability. Economic stresses are
      driven by higher patient acuity, by multiple subspecialty service and call
      demands, by high-risk obstetric services, and by long case durations attributable
      to both case complexity and time for teaching. An unfavorable payer mix,
      university taxation, and other costs associated with academic education and
      research missions further compound these stresses. In addition, the current
      economic climate and the uncertainty surrounding health care reform measures will
      continue to increase performance pressures on hospitals and anesthesiology
      departments.Although many researchers have published on the mechanics of
      operating room (OR) productivity, their investigations do not usually address the
      motivational forces that drive individual and group behaviors. Institutional
      tradition, surgical convenience, and parochial interests continue to play
      predominant roles in OR governance and scheduling practices. Efforts to redefine
      traditional relationships, to coordinate operational decision-making processes,
      and to craft incentives that align individual performance goals with those of the
      institution are all essential for creating greater economic stability. Using the
      principles of shared costs, department autonomy, hospital flexibility and control
      over institutional issues, and alignment between individual and institutional
      goals, the authors developed a template to redefine the hospital-anesthesiology
      department relationship. Here, they describe both this contractual template and
      the results that followed implementation (2007-2009) at one institution.

PMID- 22373633
TI  - Teaching techniques in the operating room:  the importance of perceptual motor
      teaching.
AB  - PURPOSE: To identify sucessful teaching techniques in the operating room
      environment through examining the teaching of the midurethral sling (MUS)
      surgery. METHOD: The authors distributed questionnaires with open-ended questions
      about teaching and learning MUS to 5 urogynecology attendings and 16 obstetrics
      gynecology residents in spring 2010. In an effort to identify qualities of an
      effective sling teacher, the authors used grounded theory to determine common
      themes and to code participant responses for examples. RESULTS: Of 21 potential
      respondents, 14 (67%) returned questionnaires. The authors analyzed these and
      identified seven commonalities among effective sling teachers: they (1) emphasize
      anatomical landmarks (as determined by 64 total comments); (2) use perceptual
      motor teaching (PMT; 38 comments); (3) encourage repetition (28); (4) promote
      early independence (34); (5) demonstrate confident competence (23); (6) maintain
      a calm demeanor in the operating room (20); and (7) exhibit a willingness to
      accept responsibility for mistakes and consequences (9). The second-most common
      attribute, using PMT, requires the teaching attending to emphasize the motor and
      tactile aspects of operating and involves incorporating not only what learners
      see but also what they feel. CONCLUSIONS: The authors report seven qualities or
      techniques fundamental to good teaching practice in a high-stress, high
      technology surgical environment, and they have identified the use of PMT, which
      to their knowledge has not been previously described. Teachers and learners in
      this study characterized PMT, which is likely generalizable to surgical
      procedures other than the MUS, as important. Future research should focus on
      exploring this technique in other surgeries.

PMID- 22373634
TI  - From hagfish to humans:  teaching comparative physiology to internal medicine
      residents.
AB  - With more clinical information for trainees to master in the face of increasing
      time pressures, discussions about underlying physiology and the mechanisms of
      disease seem to have been de-emphasized during residency training. This reduced
      focus on pathophysiology and basic science may weaken trainees' clinical
      effectiveness and reduce their interest in pursuing research careers.In response,
      the authors helped to develop in 2006 a one-week immersive comparative physiology
      course for second- and third-year internal medicine residents at Beth Israel
      Deaconess Medical Center. The course, held at the Mount Desert Island Biological
      Laboratory, includes four modules (hematology, vascular physiology, secretory
      physiology, and salt and water homeostasis), each composed of basic science
      experiments using aquatic species and accompanied by clinical correlation
      discussions and group presentations.From 2007 to 2010, 72 residents rotated
      through the course. Most reported that it enhanced their understanding of the
      mechanisms of disease in their patients. After the course, residents reported
      that physiology played a more prominent role in their teaching and clinical
      decision making during both ward and intensive care unit rotations. They also
      reported being more likely than before the course to read about the
      pathophysiology of disease when faced with a clinical problem.Although cost
      intensive and geographically unique, this model for teaching the mechanisms of
      disease could be applied elsewhere with the help of physician-scientists and
      clinician-educators. In this article, the authors describe the development of the
      course, share preliminary data evaluating progress toward its goals, and discuss
      future directions and lessons learned.

PMID- 22373635
TI  - A peer mentoring group for junior clinician educators:  four years' experience.
AB  - PURPOSE: To study the effect of a peer mentoring group (PMG). METHOD: Six junior
      clinician educator faculty and one senior faculty at the University of Washington
      Medical Center's Department of Psychiatry formed a PMG in 2006. The PMG had 30
      meetings during 2006-2010. Group format, goals, and meeting agendas were
      determined solely by participants. Feedback about positive and negative outcomes
      of participation in the PMG was determined by open-ended response to three sets
      of questions; qualitative analysis was performed by an outside research
      consultant. RESULTS: Program evaluation revealed benefits and undesirable or
      unintended outcomes. Reported benefits were increased workplace satisfaction;
      improved social connection; increased professional productivity and personal
      growth/development through accountability, collaboration, mutual learning,
      support, and information sharing; synergy, collaboration, and diversity of
      thought; increased involvement in professional activities; opportunity for peer
      discussions in a safe environment; and increased accountability and motivation.
      Undesirable or unintentional outcomes were exclusivity, lack of hierarchy,
      scheduling of meetings, absence of an intentional curriculum, diverse and
      competing interests, personal-professional enmeshment, and occasional loss of
      focus due to overemphasis on personal matters. Every member of the PMG was
      retained, and scholarly productivity increased, as did collaboration with other
      group members. CONCLUSIONS: Participants in this PMG experienced qualitative
      benefits and perceived advantages in career advancement and scholarly
      productivity. Negative consequences did not deter participation in the PMG or
      outweigh benefits. The self-sufficient and low-cost structure makes it
      particularly portable.

PMID- 22373638
TI  - AM last page. Understanding qualitative and quantitative research paradigms in
      academic medicine.

PMID- 22373639
TI  - Morphophysiological analyses of Neochloris oleoabundans (Chlorophyta) grown
      mixotrophically in a carbon-rich waste product.
AB  - Neochloris oleoabundans is considered one of the most promising oil-rich
      microalgae because of its ability to store lipids under nitrogen starvation.
      However, high biomass densities, required for applications on medium to large
      scale, are not reached in this condition of growth. As previous studies on other
      microalgae have shown that mixotrophy allows to obtain higher biomass in
      comparison to autotrophic cultures, we performed morphophysiological analyses in
      order to test the mixotrophic growth capability of N. oleoabundans. A carbon-rich
      manure derived from the apple vinegar production (AWP) was added to the medium.
      Cells were also cultivated under nutrient starvation (tap water), to observe the
      expected lipids accumulation, and combining AWP to water, to test the potential
      of this waste in a low-cost culture system. The results highlighted that AWP in
      the medium allowed to obtain the highest final cell density. Moreover, starch
      granules were stored inside chloroplast at the beginning of the experiment. The
      presence of AWP did not induce variations on light harvesting complex II (LHCII)
      photosystem II (PSII) assembly, even if an interesting promotion of pigment
      synthesis in cells was observed. On the other hand, in starved cells, chloroplast
      degeneration, pigment content decrease, altered LHCII-PSII assembly and
      accumulation of high amount of lipid globules were observed, irrespective of the
      presence of AWP. The results suggest that mixotrophy promotes growth in N.
      oleoabundans and open up the possibility of using waste products from agri-food
      industries for this purpose. After growth, cells could be transferred under
      nutrient starvation to induce lipid accumulation.

PMID- 22373640
TI  - Gross motor development is delayed following early cardiac surgery.
AB  - OBJECTIVE: To describe the gross motor development of infants who had undergone
      cardiac surgery in the neonatal or early infant period. METHODS: Gross motor
      performance was assessed when infants were 4, 8, 12, and 16 months of age with
      the Alberta Infant Motor Scale. This scale is a discriminative gross motor
      outcome measure that may be used to assess infants from birth to independent
      walking. Infants were videotaped during the assessment and were later evaluated
      by a senior paediatric physiotherapist who was blinded to each infant's medical
      history, including previous clinical assessments. Demographic, diagnostic,
      surgical, critical care, and medical variables were considered with respect to
      gross motor outcomes. RESULTS: A total of 50 infants who underwent elective or
      emergency cardiac surgery at less than or up to 8 weeks of age, between July 2006
      and January 2008, were recruited to this study and were assessed at 4 months of
      age. Approximately, 92%, 84%, and 94% of study participants returned for
      assessment at 8, 12, and 16 months of age, respectively. Study participants had
      delayed gross motor development across all study time points; 62% of study
      participants did not have typical gross motor development during the first year
      of life. Hospital length of stay was associated with gross motor outcome across
      infancy. CONCLUSION: Active gross motor surveillance of all infants undergoing
      early cardiac surgery is recommended. Further studies of larger congenital heart
      disease samples are required, as are longitudinal studies that determine the
      significance of these findings at school age and beyond.

PMID- 22373642
TI  - Brain energy metabolism and blood flow differences in healthy aging.
AB  - Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow
      (CBF), and oxygen extraction fraction (OEF) are important indices of healthy
      aging of the brain. Although a frequent topic of study, changes of CBF and
      CMRO(2) during normal aging are still controversial, as some authors find
      decreases of both CBF and CMRO(2) but increased OEF, while others find no change,
      and yet other find divergent changes. In this reanalysis of previously published
      results from positron emission tomography of healthy volunteers, we determined
      CMRO(2) and CBF in 66 healthy volunteers aged 21 to 81 years. The magnitudes of
      CMRO(2) and CBF declined in large parts of the cerebral cortex, including
      association areas, but the primary motor and sensory areas were relatively
      spared. We found significant increases of OEF in frontal and parietal cortices,
      excluding primary motor and somatosensory regions, and in the temporal cortex.
      Because of the inverse relation between OEF and capillary oxygen tension,
      increased OEF can compromise oxygen delivery to neurons, with possible
      perturbation of energy turnover. The results establish a possible mechanism of
      progression from healthy to unhealthy brain aging, as the regions most affected
      by age are the areas that are most vulnerable to neurodegeneration.

PMID- 22373641
TI  - Notch and disease: a growing field.
AB  - Signals through the Notch receptors are used throughout development to control
      cellular fate choices. Our intention here is to provide an overview of the
      involvement of Notch signaling in human disease, which, keeping pace with the
      known biology of the pathway, manifests itself in a pleiotropic fashion. A
      pathway with such broad action in normal development, a profound involvement in
      the biology of adult stem cells and intricate and complex controls governing its
      activity, poses numerous challenges. We provide an overview of Notch related
      pathologies identified thus far and emphasize aspects that have been modeled in
      experimental systems in order to understand the underlying pathobiology and,
      hopefully, help the definition of rational therapeutic avenues.

PMID- 22373644
TI  - The search for sensitive biomarkers in presymptomatic Huntington disease.

PMID- 22373643
TI  - pH as a biomarker of neurodegeneration in Huntington's disease: a translational
      rodent-human MRS study.
AB  - Early diagnosis and follow-up of neurodegenerative diseases are often hampered by
      the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance
      spectroscopy (MRS) offer promising tools to detect biochemical alterations at
      early stages of degeneration. Intracellular pH, which can be measured
      noninvasively by (31)P-MRS, has shown variations in several brain diseases. Our
      purpose has been to evaluate the potential of MRS-measured pH as a relevant
      biomarker of early degeneration in Huntington's disease (HD). We used a
      translational approach starting with a preclinical validation of our hypothesis
      before adapting the method to HD patients. (31)P-MRS-derived cerebral pH was
      first measured in rodents during chronic intoxication with 3-nitropropionic acid
      (3NP). A significant pH increase was observed early into the intoxication
      protocol (pH=7.17+/-0.02 after 3 days) as compared with preintoxication
      (pH=7.08+/-0.03). Furthermore, pH changes correlated with the 3NP-induced
      inhibition of succinate dehydrogenase and preceded striatum lesions. Using a
      similar MRS approach implemented on a clinical MRI, we then showed that cerebral
      pH was significantly higher in HD patients (n=7) than in healthy controls (n=6)
      (7.05+/-0.03 versus 7.02+/-0.01, respectively, P=0.026). Altogether, both
      preclinical and human data strongly argue in favor of MRS-measured pH being a
      promising biomarker for diagnosis and follow-up of HD.

PMID- 22373645
TI  - Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular
      dysfunction and infarction during mild but not severe hyperglycemic stroke.
AB  - We investigated mechanisms by which circulating factors during hyperglycemic (HG)
      stroke affect cerebrovascular function and the role of peroxynitrite in stroke
      outcome. Middle cerebral arteries (MCAs) were isolated from male Wistar rats and
      perfused with plasma from rats that were hyperglycemic for 5 to 6 days by
      streptozotocin and underwent either MCA occlusion (HG MCAO) or Sham surgery (HG
      Sham) compared with MCA perfused with physiologic saline (No plasma). Myogenic
      responses and endothelial function were compared in untreated MCA (n=8/group) or
      with inhibitors of NADPH oxidase (apocynin; n=8), peroxynitrite (FeTMPyP; n=8) or
      endothelin-1 (ET-1)(A) (BQ-123; n=8). Finally, animals were treated in vivo
      before reperfusion after mild (<68% cerebral blood flow (CBF) decrease) or severe
      (>68% CBF decrease) MCAO with FeTMPyP (n=12) or vehicle (n=12) and CBF and
      infarction measured. The HG MCAO plasma increased tone in MCA versus No plasma
      (P<0.05) that was reversed by FeTMPyP, but not by apocynin or BQ-123. The HG Sham
      plasma also increased tone in MCA (P<0.05) that was reversed by BQ-123 only. In
      vivo, FeTMPyP was neuroprotective during mild, but not severe ischemia. These
      results show that circulating factors in plasma can affect cerebrovascular
      function through peroxynitrite generation and ET-1. In addition, peroxynitrite
      decomposition improves stroke outcome acutely during mild, but not severe HG
      ischemia.

PMID- 22373646
TI  - Watermaze performance after middle cerebral artery occlusion in the rat: the role
      of sensorimotor versus memory impairments.
AB  - In rodent stroke models, investigation of deficits in spatial memory using the
      Morris watermaze may be confounded by coexisting sensory or motor impairments. To
      target memory specifically, we devised a watermaze protocol to minimize the
      impact of sensory and motor impairments in female Lister-hooded rats exposed to
      proximal electrocoagulation of the middle cerebral artery (MCAO). Rats were
      trained in a reference-memory task comprising 4 trials/day; trial 1 being a probe
      trial (platform absent for the first 60 seconds). Training ended once animals
      reached a strict criterion based on the probe-trial performance. Memory retention
      was tested 1, 7, and 28 days later. The MCAO did not affect the number of days to
      reach criterion during acquisition or the time spent in target quadrant during
      retention testing, compared with sham or unoperated rats. However, MCAO rats
      showed slightly poorer accuracy in crossing the platform location and increased
      thigmotactic swimming compared with controls. Our results show that spatial
      memory deficits are minimal in this rodent stroke model, and suggest that
      previously published watermaze impairments are attributable to sensory and motor
      deficits but not memory deficits. We recommend using probe trials and training to
      a predetermined performance criterion in future studies assessing watermaze
      memory deficits in rodent stroke models.

PMID- 22373647
TI  - Brain slices from glutaminase-deficient mice metabolize less glutamine: a
      cellular metabolomic study with carbon 13 NMR.
AB  - In the brain, glutaminase is considered to have a key role in the provision of
      glutamate, a major excitatory neurotransmitter. Brain slices obtained from wild
      type (control) and glutaminase-deficient (GLS1+/-) mice were incubated without
      glucose and with 5 or 1 mmol/L [3-(13)C]glutamine as substrate. At the end of the
      incubation, substrate removal and product formation were measured by both
      enzymatic and carbon 13 nuclear magnetic resonance ((13)C-NMR) techniques. Slices
      from GLS1+/- mice consumed less [3-(13)C]glutamine and accumulated less [3
      (13)C]glutamate. They also produced less (13)CO(2) but accumulated amounts of
      (13)C-aspartate and (13)C-gamma-aminobutyric acid (GABA) that were similar to
      those found with brain slices from control mice. The newly formed glutamine
      observed in slices from control mice remained unchanged in slices from GLS1+/-
      mice. As expected, flux through glutaminase in slices from GLS1+/- mice was found
      diminished. Fluxes through all enzymes of the tricarboxylic acid cycle were also
      reduced in brain slices from GLS1+/- mice except through malate dehydrogenase
      with 5 mmol/L [3-(13)C]glutamine. The latter diminutions are consistent with the
      decreases in the production of (13)CO(2) also observed in the slices from these
      mice. It is concluded that the genetic approach used in this study confirms the
      key role of glutaminase for the provision of glutamate.

PMID- 22373648
TI  - How much does the amphioxus genome represent the ancestor of chordates?
AB  - One of the main motivations to study amphioxus is its potential for understanding
      the last common ancestor of chordates, which notably gave rise to the
      vertebrates. An important feature in this respect is the slow evolutionary rate
      that seems to have characterized the cephalochordate lineage, making amphioxus an
      interesting proxy for the chordate ancestor, as well as a key lineage to include
      in comparative studies. Whereas slow evolution was first noticed at the
      phenotypic level, it has also been described at the genomic level. Here, we
      examine whether the amphioxus genome is indeed a good proxy for the genome of the
      chordate ancestor, with a focus on protein-coding genes. We investigate genome
      features, such as synteny, gene duplication and gene loss, and contrast the
      amphioxus genome with those of other deuterostomes that are used in comparative
      studies, such as Ciona, Oikopleura and urchin.

PMID- 22373649
TI  - Focus on miRNAs evolution: a perspective from amphioxus.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene
      expression and thus control diverse biological processes. The high interest in
      miRNAs as an important mediator of post-transcriptional gene regulation has led
      to the discovery of miRNAs in several organisms. The present article outlines and
      discusses the current status of miRNAs information on the basal chordate
      amphioxus and the evolution of miRNAs in metazoans.

PMID- 22373650
TI  - Amino acid transport system A is involved in inflammatory nociception in rats.
AB  - Previous studies have indicated that central sensitization is a state of
      increased excitability of nociceptive neurons in the spinal dorsal horn following
      peripheral tissue injury and/or inflammation and astrocytes play an important
      role in the central sensitization. The current study investigated the role of
      amino acid transport system A in central sensitization and hyperalgesia induced
      by intraplantar injection of formalin in rats. Formalin (5%, 50MUl) injected
      subcutaneously into the unilateral hindpaw pad induced typical biphase
      nociceptive behaviors, including licking/biting and flinching of the injected paw
      and an increase of glial fibrillary acid protein (GFAP, an activated astrocyte
      marker) expression in spinal dorsal horn, and these effects could be attenuated
      by intrathecal injection of the competitive inhibitor of amino acid system A
      transporter, methylaminoisobutyric acid (MeAIB, 0.1, 0.3, 0.5, and 0.7mmol), in a
      dose-dependent manner. Intrathecal injection of vehicle (PBS) had no effect on
      the formalin-induced nociceptive behaviors and increase of the GFAP. These
      findings suggest that amino acid transport system A is involved in inflammation
      induced nociception, and inhibition of this transporter system results in
      inhibition of the central sensitization and hyperalgesia.

PMID- 22373651
TI  - BDNF and NT-3 expression by using glucocorticoid-induced bicistronic expression
      vector pGC-BDNF-IRES-NT3 protects apoptotic cells in a cellular injury model.
AB  - Spinal cord injury (SCI) is a severe traumatic disease in the central nervous
      system with high incidence and high morbidity. Recent study demonstrated that
      cell transplantation therapy may improve local microenvironment of the injury
      site and promote nerve regeneration to restore spinal cord functions. In this
      study, we constructed a glucocorticoid-induced bicistronic eukaryotic expression
      vector pGC-BDNF-IRES-NT3 by using molecular cloning techniques and examined the
      protective effect of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor
      (BDNF) expressed by this vector in a rat spinal cord injury (SCI) model. We first
      connected glucocorticoid response element (GRE) to cytomegalovirus (CMV) promoter
      and then the GRE-CMV gene was inserted into pEGFP-1 vector to construct the
      eukaryotic expression vector pGC-EGFP. Western blot analysis was used to confirm
      the expression of EGFP by transfecting this vector in RN-DSC cells. The IRES was
      used to connect BDNF gene and NT-3 gene and replaced the EGFP gene in pGC-EGFP
      plasmid to form the bicistronic expression vector-pGC-BDNF-IRES-NT3. After RN-DSC
      cells were transfected with the plasmid and treated with glucocorticoid, BDNF and
      NT-3 expression in the culture medium were measured by ELISA method. Finally, we
      found that combination therapy with the transfection of this vector and
      glucocorticoid had an anti-apoptotic effect in a cellular SCI model of RN-DSC
      cells. Therefore, the co-expression of BDNF and NT-3 by using this vector rescued
      the injured cells. This provided useful information for the gene-modification
      cell transplantation combined with glucocorticoid for the treatment of SCI.

PMID- 22373652
TI  - On the role of volume transmission and receptor-receptor interactions in social
      behaviour: focus on central catecholamine and oxytocin neurons.
AB  - This article is focused on understanding the mechanisms for the interactions
      between the central catecholamine (CA) and oxytocin (OXY) neurons and their
      relevance for brain function especially social behaviour in the field of pair
      bonding. Such a topic is analysed under two perspectives namely the intercellular
      communication modes between CA and OXT neurons and the molecular integrative
      mechanisms at the plasma membrane level between their respective decoding
      systems. As a matter of fact, recent observations strongly indicate a major role
      of volume transmission and receptor-receptor interactions in the CA/OXT neuron
      interplay in the brain control of social behaviour and pair bonding. This article
      is part of a Special Issue entitled: Brain Integration.

PMID- 22373653
TI  - Association of influenza virus infection and inflammatory cytokines with acute
      myocardial infarction.
AB  - OBJECTIVE: To explore the potential relationship between previous influenza virus
      (IV) infection and acute myocardial infarction (AMI), and the mechanism of
      atherosclerosis, we conducted a case-control study and examined inflammatory
      cytokines to assess the association of previous IV infection and AMI. METHODS: A
      questionnaire-based survey was conducted to collect information about demographic
      characteristics and heart disease risk factors. Fasting blood samples were
      obtained to measure immunoglobulin (Ig) G antibodies to influenza virus A (IV-A),
      influenza virus B (IV-B), cytomegalovirus, herpes simplex virus type-1 and type
      2, adenovirus, rubella virus and Chlamydia pneumoniae, and to measure the level
      of certain biochemistry markers: interleukin-2, 6, 10 and 18 (IL-2, 6, 10 and
      18), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma),
      endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1) and
      soluble vascular cell adhesion molecule-1 (sVCAM-1). RESULTS: Compared with the
      controls, the cases were more likely to have positive IgG antibodies to IV-A and
      IV-B [IV-A: odds ratio (OR): 3.1, 95% confidence interval (CI): 1.5-6.4; IV-B:
      OR: 10.2, 95% CI: 5.7-20.0]. After adjustment for potential confounding
      variables, the risk of AMI was still associated with the presence of IgG
      antibodies to IV-A (adjusted OR: 5.5, 95% CI: 1.3-23.0) and IV-B (adjusted OR:
      20.3, 95% CI: 5.6-40.8). The levels of IL-2, 6, 10 and18, TNF-alpha, IFN-gamma,
      ET-1, sICAM-1 and sVCAM-1 in patients with AMI were significantly higher than
      those of the controls (P < 0.01). CONCLUSIONS: Our study supports the hypothesis
      that previous IV infection is associated with AMI. Inflammatory cytokines may
      take part in the development of atherosclerosis and trigger the occurrence of
      AMI.

PMID- 22373654
TI  - Commentary to 'Long-term results of endoscopic treatment of vesicoureteral reflux
      in children with different materials'.

PMID- 22373655
TI  - Commentary to 'Repair oriented categorization of circumcision urethral injury in
      Benin City, Nigeria'.

PMID- 22373656
TI  - The antifibrotic drug halofuginone reduces ischemia/reperfusion-induced oxidative
      renal damage in rats.
AB  - AIM: The objective of the present study was to evaluate the protective effects of
      halofuginone against renal ischemia/reperfusion (I/R) injury. MATERIALS AND
      METHODS: Male Wistar albino rats were unilaterally nephrectomized and the left
      renal pedicles were occluded for 45 min to induce ischemia and then reperfused
      for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with
      either halofuginone (100 MUg/kg/day) or saline 30 min prior to ischemia and the
      dose was repeated in the late reperfusion groups. In the sham groups, rats
      underwent unilateral nephrectomy and were treated at similar time points. The
      animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and
      kidney samples were obtained. RESULTS: I/R injury increased renal malondialdehyde
      levels, myeloperoxidase activity and reactive oxygen radical levels, and
      decreased the renal glutathione content. Halofuginone treatment was found to
      reduce oxidative I/R injury and improve renal function in the rat kidney, as
      evidenced by reduced generation of reactive oxygen species, depressed lipid
      peroxidation and myeloperoxidase activity, and increased glutathione levels.
      CONCLUSIONS: The present findings demonstrate the anti-inflammatory and
      antioxidant effects of halofuginone in renal I/R injury, supporting its potential
      use where renal I/R injury is inevitable.

PMID- 22373657
TI  - Brain mechanisms for emotional influences on perception and attention: what is
      magic and what is not.
AB  - The rapid and efficient selection of emotionally salient or goal-relevant stimuli
      in the environment is crucial for flexible and adaptive behaviors. Converging
      data from neuroscience and psychology have accrued during the last decade to
      identify brain systems involved in emotion processing, selective attention, and
      their interaction, which together act to extract the emotional or motivational
      value of sensory events and respond appropriately. An important hub in these
      systems is the amygdala, which may not only monitor the emotional value of
      stimuli, but also readily project to several other areas and send feedback to
      sensory pathways (including striate and extrastriate visual cortex). This system
      generates saliency signals that modulate perceptual, motor, as well as memory
      processes, and thus in turn regulate behavior appropriately. Here, we review our
      current views on the function and properties of these brain systems, with an
      emphasis on their involvement in the rapid and/or preferential processing of
      threat-relevant stimuli. We suggest that emotion signals may enhance processing
      efficiency and competitive strength of emotionally significant events through
      gain control mechanisms similar to those of other (e.g. endogenous) attentional
      systems, but mediated by distinct neural mechanisms in amygdala and
      interconnected prefrontal areas. Alterations in these brain mechanisms might be
      associated with psychopathological conditions, such as anxiety or phobia. We
      conclude that attention selection and awareness are determined by multiple
      attention gain control systems that may operate in parallel and use different
      sensory cues but act on a common perceptual pathway.

PMID- 22373658
TI  - Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are
      poor substrates for commercial aryl-sulfatases: implications for studies
      concerned with quantifying epicatechin bioavailability.
AB  - Epicatechin is a widely consumed dietary flavonoid and there is substantial
      evidence that it contributes to the health benefits reported for flavanol-rich
      cocoa products including dark chocolate. Numerous reports have described the
      appearance of epicatechin and epicatechin phase-2 conjugates (sulfates and
      glucuronides of epicatechin and methylepicatechin) in blood and urine samples of
      subjects following ingestion of epicatechin. The most widely reported method of
      quantifying total epicatechin in plasma and urine samples involves hydrolysis
      with a mixture of beta-glucuronidase and sulfatase to convert the conjugates to
      epicatechin aglycone which is subsequently quantified. We observed a lack of
      hydrolysis of epicatechin sulfates and methylepicatechin sulfates using
      commercial sulfatases and investigated this further. Samples of urine or plasma
      from subjects who had consumed epicatechin were subjected to enzyme hydrolysis
      and then analysed using LC-MS/MS, or analysed without enzyme hydrolysis. Attempts
      to increase the extent of hydrolysis of epicatechin conjugates were made by
      increasing the amount of enzyme, hydrolysis pH and length of incubations, and
      using alternative sources of enzyme. The standard hydrolysis conditions failed to
      hydrolyse the majority of epicatechin sulfates and methylepicatechin sulfates.
      Even when the quantity of enzyme and incubation period was increased, the pH
      optimised, or alternative sources of sulfatases were used, epicatechin
      monosulfates and methylepicatechin monosulfates remained as major peaks in the
      chromatograms of the samples. An assessment of literature data strongly suggested
      that the majority of reports where enzyme hydrolysis was used had significantly
      underestimated epicatechin bioavailability in humans. Methods for quantifying
      epicatechin concentrations in blood and urine need to take account of the lack of
      hydrolysis of (methyl)epicatechin-sulfates, for example by quantifying these
      directly using LC-MS/MS.

PMID- 22373660
TI  - Continuous furosemide infusion in the management of ascites.
AB  - BACKGROUND: The current therapy for patients hospitalized with ascites requires
      titration of oral diuretics and often needs several days. A faster method for
      predicting the response to a given dose of diuretic may allow this process to be
      completed more rapidly. AIM: The objective of this study was to describe the
      short-term safety and efficacy of a diuretic infusion to predict net sodium
      excretion in patients with cirrhosis, ascites, and edema using a fractional
      excretion of sodium (FENa) of 1% or greater as the target. METHODS: We conducted
      a retrospective case series of patients admitted for management of ascites who
      received intravenous furosemide by continuous infusion in ascites management.
      Patients were stratified depending on whether they had edema or received an
      intravenous bolus of furosemide or a large-volume paracentesis. The primary
      outcome was the proportion of patients achieving a FENa of 1% or greater during
      the infusion. Secondary outcomes included development of electrolyte
      abnormalities or acute kidney injury during or immediately following the infusion
      and natriuresis on titrated oral furosemide. RESULTS: Forty-seven patients
      meeting criteria were identified from 721 patients seen in consultation. Ten of
      the patients had edema and received neither bolus intravenous diuretic therapy
      nor therapeutic paracentesis; all 10 achieved a FENa of 1% or greater. One
      patient had transient hypokalemia. Of 37 patients who either had no edema or
      received additional treatment options, all but 6 patients achieved a FENa of 1%
      or greater. Transient complications in 31 patients with natriuresis included
      hyponatremia (n = 1), hypokalemia (n = 5), and acute kidney injury (n = 3).
      Twenty-four-hour urine sodium averaged more than 4 g/d on the titrated oral
      furosemide regimen in 19 patients completing the collection. CONCLUSIONS: Use of
      a short continuous furosemide infusion can achieve a FENa of 1% or greater in
      patients with cirrhotic ascites and may be safe and efficacious for diuresis,
      meriting further study.

PMID- 22373659
TI  - Differential expression of PAI-RBP1, C1orf142, and COTL1 in non-small cell lung
      cancer cell lines with different tumor metastatic potential.
AB  - Human non-small cell lung cancer (NSCLC) is one of the most common malignancies
      in the modern world. Its recurrence is mainly due to its ability to invade and
      metastasize. However, the precise mechanism for tumor development and metastasis
      is still not fully understood. To shed light on the development of lung cancer,
      the human giant cell lung carcinoma cell lines 95D with high metastatic potential
      and 95C with low metastatic potential were selected in this study. The 2 cell
      lines originated from the same parental cell and share a similar genetic
      background. In the current study, we identified 3 differentially expressed
      proteins in 95C and 95D cell lines, namely, PAI-RBP1, C1orf142, and COTL1, by
      using 2-dimensional electrophoresis proteomics analysis. We found that PAI-RBP1
      and C1orf142 expression levels were higher in 95D than in 95C cells, whereas
      COTL1 expression level was lower in 95D when compared to 95C cells. We also
      confirmed these results by reverse transcription-polymerase chain reaction and
      immunoblotting analyses. The messenger RNA and protein levels of PAI-RBP1 and
      C1orf142 were much higher in 95D than in 95C cells, and COTL1 expression level
      was lower in 95D than in 95C cells. The PAI-RBP1 expression was assessed by
      immunohistochemistry in 70 NSCLC and 7 normal lung tissue samples from patients.
      PAI-RBP1 expression level was higher in tumor tissues (positive staining in 87.1%
      of cases [61/70]) than in normal tissues (positive staining in 14.3% of cases
      [1/7]). In conclusion, by studying protein expression in NSCLC cell lines with
      high and low metastasis as well as in human lung cancer tissues, we have
      identified 3 proteins, namely, PAI-RBP1, C1orf142, and COTL1, which were
      differentially expressed in NSCLC cell lines with different metastatic potential.
      In addition, we also found that PAI-RBP1 might contribute to NSCLC development.

PMID- 22373661
TI  - Echocardiogram done early in neonatal sepsis:  what does it add?
AB  - BACKGROUND: One of the major organs affected in neonatal sepsis is the heart.
      Echocardiogram provides real-time information on the cardiovascular performance
      rather than dependence on the clinical signs alone, which might lead to
      misjudgment. AIM OF THE WORK: To assess left ventricular (LV) functions in septic
      neonates early after admission using transthoracic color Doppler
      Echocardiography. PATIENTS AND METHODS: Echocardiography was done to 30 septic
      and 30 nonseptic newborns who were divided among 4 groups (septic full-term, 14;
      septic preterm, 16; nonseptic full-term, 21; and nonseptic preterm, 9).
      Comparisons were made among the 4 groups using analysis of variance and post hoc
      test regarding the systolic function (using ejection fraction and fractional
      shortening), the diastolic function (using the early patrial peak/atrial peak
      flow velocity ratio), and the global LV function (using myocardial performance
      index). RESULTS: The E-wave and the early peak flow velocity/atrial peak flow
      velocity ratio were significantly lower in the septic neonates, whether full-term
      or premature, compared to their corresponding age groups in the nonseptic
      newborns, suggesting LV diastolic dysfunction (P < 0.001 and P < 0.014,
      respectively). No difference was found in the diastolic function between the full
      term and the preterm neonates whether lying within the septic group or in the
      nonseptic group. Myocardial performance index was significantly higher in the
      septic neonates who died than in the survivors (P < 0.001). CONCLUSION: Neonatal
      sepsis is associated with LV diastolic dysfunction.

PMID- 22373662
TI  - Cystatin C levels in patients with dipper and nondipper hypertension.
AB  - OBJECTIVE: Subjects with nondipper hypertension carry a higher risk of
      cardiovascular events than their normotensive counterparts. The present study was
      designed to investigate cystatin C levels in patients with dipper and nondipper
      hypertension. METHODS: Eighty-eight consecutive patients who had been treated
      with antihypertensive drugs for at least 6 months were included in the study.
      Dipping and nondipping patterns were detected with ambulatory blood pressure
      monitoring. Clinical, laboratory, and ambulatory blood pressure monitoring data
      of patient groups with nondipper and dipper hypertension were compared. RESULTS:
      Patients in the nondipper group were older than those in the dipper group. Serum
      cystatin C level was higher in the patients in the nondipper group. Cystatin C
      was negatively correlated with the rate of systolic blood pressure fall at night
      (r = -0.41; P < 0.001). Linear regression analyses revealed that only cystatin C
      level was a significant correlate of nocturnal systolic blood pressure decrease.
      Logistic regression analyses also showed that cystatin C was an independent
      predictor of nondipping pattern (odds ratio, 3.586; 95% confidence interval,
      1.432-8.98; P = 0.006]). CONCLUSION: The present study showed that cystatin C is
      higher in patients with nondipper hypertension patients.

PMID- 22373664
TI  - Prevalence of fibromyalgia syndrome in patients referred to a tertiary pain
      clinic.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS), the prototypical central pain
      augmentation syndrome, is characterized by widespread pain and tenderness.
      Although patients referred to tertiary care pain clinics are recognized as
      suffering from chronic pain, they are generally considered to have pain
      attributable to discrete peripheral, nociceptive, or neuropathic etiology.The
      purpose of the current study was to assess the prevalence of FMS among
      consecutive patients referred to a tertiary pain clinic and to evaluate the
      contribution of central pain to the clinical impact upon such patients. METHODS:
      Eighty-five consecutive patients (38 were male, and 47 were female) attending a
      pain clinic were assessed for the presence of FMS. The presence of FMS was
      determined according to the 1990 American College of Rheumatology (ACR)
      classification criteria. Quality of life and physical functioning were assessed,
      utilizing a structured questionnaire. RESULTS: The ACR criteria for the
      classification of FMS were fulfilled by 41.2% of patients. Patients fulfilling
      FMS criteria ranked significantly lower on all domains of the SF-36, including
      general health, physical functioning, role limitation due to physical and
      emotional problems, vitality, social functioning, bodily pain, and mental health.
      Composite physical and mental health scores were significantly lower among
      patients fulfilling ACR FMS criteria. Patients fulfilling the ACR criteria for
      FMS felt significantly more tenderness, based on the mean number of tender points
      and the mean tenderness threshold, when compared with patients not fulfilling the
      ACR FMS criteria. CONCLUSIONS: A significant proportion of patients referred to a
      tertiary pain clinic were found to fulfill the ACR criteria for classification of
      FMS and thus exhibit an important element of central pain. Central pain
      augmentation should be actively searched for and therapeutically addressed in the
      evaluation and management of all patients with chronic pain.

PMID- 22373663
TI  - Sex differences in cardiovascular disease risk and exercise in type 2 diabetes.
AB  - Diabetes currently affects approximately 14% of the US population, and
      cardiovascular disease (CVD) is a leading cause of morbidity and mortality in
      those with diabetes. Although in the general population women are at lower risk
      than men for CVD, women have a disproportionately greater increase in risk for
      CVD than do men in the context of diabetes. Physical activity is considered a
      cornerstone in the prevention and treatment of CVD and its risk factors, but
      greater barriers to physical activity may exist for women with diabetes compared
      to their male counterparts. In this article, we review sex differences in CVD
      incidence and risk among diabetics, sex differences in physical activity
      behaviors, cardiovascular abnormalities and impaired exercise capacity in women
      living with diabetes, and the effects of exercise on prevention and treatment of
      CVD in diabetic women. Finally, we discuss future research needed to clarify
      potential sex differences in the cardiovascular effects of diabetes and to
      establish ways to reduce the barriers to exercise in women with diabetes.

PMID- 22373665
TI  - Hofmeister series reversal for lysozyme by change in pH and salt concentration:
      insights from electrophoretic mobility measurements.
AB  - Hofmeister series reversal can occur with change in pH, or increase in salt
      concentration. The phenomena are a challenge for any theory of ion specific
      effects. Recent theoretical work predicts how a complex interplay between ionic
      sizes, hydration and dispersion forces explains Hofmeister series reversal.
      Electrophoretic mobility measurements on lysozyme suspensions reported here are
      consistent with the theory.

PMID- 22373666
TI  - Fluorescence imaging of the lymph node uptake of proteins in mice after
      subcutaneous injection: molecular weight dependence.
AB  - PURPOSE: To use noninvasive fluorescence imaging to investigate the influence of
      molecular weight (MW) of proteins on the rate of loss from a subcutaneous (SC)
      injection site and subsequent uptake by the draining lymph nodes in mice.
      METHODS: Bevacizumab (149 kDa), bovine serum albumin (BSA, 66 kDa), ovalbumin
      (44.3 kDa) or VEGF-C156S (23 kDa), labeled with the near infrared dye IRDye 680,
      were injected SC into the front footpad of SKH-1 mice. Whole body non-invasive
      fluorescence imaging was performed to quantitate the fluorescence signal at the
      injection site and in axillary lymph nodes. RESULTS: The half-life values,
      describing the times for 50% loss of proteins from the injection site, were 6.81
      h for bevacizumab, 2.85 h for BSA, 1.57 h for ovalbumin and 0.31 h for VEGF
      C156S. The corresponding axillary lymph node exposure, represented as the area of
      the % dose versus time curve, was 6.27, 5.13, 4.06 and 1.54% dose ? h,
      respectively. CONCLUSIONS: Our results indicate that the rate of loss of proteins
      from a SC injection site is inversely related to MW of proteins, while lymph node
      exposure is proportionally related to the MW of proteins in a mouse model.

PMID- 22373668
TI  - Literature-based genetic risk scores for coronary heart disease: the
      Cardiovascular Registry Maastricht (CAREMA) prospective cohort study.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified many single
      nucleotide polymorphisms (SNPs) associated with coronary heart disease (CHD) or
      CHD risk factors (RF). Using a case-cohort study within the prospective
      Cardiovascular Registry Maastricht (CAREMA) cohort, we tested if genetic risk
      scores (GRS) based on GWAS-identified SNPs are associated with and predictive for
      future CHD. METHODS AND RESULTS: Incident cases (n=742), that is, participants
      who developed CHD during a median follow-up of 12.1 years (range, 0.0-16.9
      years), were compared with a randomly selected subcohort of 2221 participants
      selected from the total cohort (n=21 148). We genotyped 179 SNPs previously
      associated with CHD or CHD RF in GWAS as published up to May 2, 2011. The allele
      count GRS, composed of all SNPs, the 153 RF SNPs, or the 29 CHD SNPs were not
      associated with CHD independent of CHD RF. The weighted 29 CHD SNP GRS, with
      weights obtained from GWAS for every SNP, were associated with CHD independent of
      CHD RF (hazard ratio, 1.12 per weighted risk allele; 95% confidence interval,
      1.04-1.21) and improved risk reclassification with 2.8% (P=0.031). As an
      exploratory approach to achieve weighting, we performed least absolute shrinkage
      and selection operator (LASSO) regression analysis on all SNPs and the CHD SNPs.
      The CHD LASSO GRS performed equal to the weighted CHD GRS, whereas the Overall
      LASSO GRS performed slightly better than the weighted CHD GRS. CONCLUSIONS: A GRS
      composed of CHD SNPs improves risk prediction when adjusted for the effect sizes
      of the SNPs. Alternatively LASSO regression analysis may be used to achieve
      weighting; however, validation in independent populations is required.

PMID- 22373669
TI  - Mortality of inherited arrhythmia syndromes: insight into their natural history.
AB  - BACKGROUND: For most arrhythmia syndromes, the risk of sudden cardiac death for
      asymptomatic mutation carriers is ill defined. Data on the natural history of
      these diseases, therefore, are essential. The family tree mortality ratio method
      offers the unique possibility to study the natural history at a time when the
      disease was not known and patients received no treatment. METHODS AND RESULTS: In
      6 inherited arrhythmia syndromes caused by specific mutations, we analyzed all
      cause mortality with the family tree mortality ratio method (main outcome
      measure, standardized mortality ratio [SMR]). In long-QT syndrome (LQTS) type 1,
      severely increased mortality risk during all years of childhood was observed (1
      19 years), in particular during the first 10 years of life (SMR, 2.9; 95% CI, 1.5
      5.1). In LQTS type 2, we observed increasing SMRs starting from age 15 years,
      which just reached significance between age 30 and 39 (SMR, 4.0; 95% CI, 1.1
      10.0). In LQTS type 3, the SMR was increased between age 15 and 19 years (SMR,
      5.8; 95% CI, 1.2-16.9). In the SCN5A overlap syndrome, excess mortality was
      observed between age 10 and 59 years, with a peak between 20 and 39 years (SMR,
      3.8; 95% CI, 2.5-5.7). In catecholaminergic polymorphic ventricular tachycardia,
      excess mortality was restricted to ages 20 to 39 years (SMR, 3.0; 95% CI, 1.3
      6.0). In Brugada syndrome, excess mortality was observed between age 40 and 59
      (SMR, 1.79; 95% CI, 1.2-2.4), particularly in men. CONCLUSIONS: We identified age
      ranges during which the mortality risk manifests in an unselected and untreated
      population, which can guide screening in these families.

PMID- 22373667
TI  - A novel "molecular tweezer" inhibitor of alpha-synuclein neurotoxicity in vitro
      and in vivo.
AB  - Aggregation of alpha-synuclein (alpha-syn) is implicated as being causative in
      the pathogenesis of Parkinson's disease, multiple system atrophy, and dementia
      with Lewy bodies. Despite several therapies that improve symptoms in these
      disorders, none slow disease progression. Recently, a novel "molecular tweezer"
      (MT) termed CLR01 has been described as a potent inhibitor of assembly and
      toxicity of multiple amyloidogenic proteins. Here we investigated the ability of
      CLR01 to inhibit assembly and toxicity of alpha-syn. In vitro, CLR01 inhibited
      the assembly of alpha-syn into beta-sheet-rich fibrils and caused disaggregation
      of pre-formed fibrils, as determined by thioflavin T fluorescence and electron
      microscopy. alpha-Syn toxicity was studied in cell cultures and was completely
      mitigated by CLR01 when alpha-syn was expressed endogenously or added
      exogenously. To determine if CLR01 was also protective in vivo, we used a novel
      zebrafish model of alpha-syn toxicity (alpha-syn-ZF), which expresses human, wild
      type alpha-syn in neurons. alpha-Syn-ZF embryos developed severe deformities due
      to neuronal apoptosis and most of them died within 48 to 72 h. CLR01 added to the
      water significantly improved zebrafish phenotype and survival, suppressed alpha
      syn aggregation in neurons, and reduced alpha-syn-induced apoptosis. alpha-Syn
      expression was found to inhibit the ubiquitin proteasome system in alpha-syn-ZF
      neurons, resulting in further accumulation of alpha-syn. Treatment with CLR01
      almost completely mitigated the proteasome inhibition. The data suggest that
      CLR01 is a promising therapeutic agent for the treatment of Parkinson's disease
      and other synucleinopathies.

PMID- 22373671
TI  - Take your pick-it's all good.

PMID- 22373672
TI  - Rheumatoid arthritis.

PMID- 22373673
TI  - Social media.

PMID- 22373675
TI  - Comprehensive sex education for teens is more effective than abstinence.

PMID- 22373676
TI  - No increased risk of genetic damage in children of cancer survivors.

PMID- 22373679
TI  - Some surgeons disregard advance directives.

PMID- 22373681
TI  - The nurse's role in health care reform at the state level.

PMID- 22373682
TI  - Alcohol consumption in women.

PMID- 22373688
TI  - The state of the science in the prevention and management of osteoarthritis.
AB  - OVERVIEW: In July 2011 a symposium on osteoarthritis convened experts in many
      areas-nursing, epidemiology, rheumatology, public policy, geriatrics,
      pharmacotherapy, physical therapy, and complementary modalities-to discuss the
      importance of nurses in reducing the disability caused by osteoarthritis. The
      planning committee included representatives from AJN, the National Association of
      Orthopaedic Nurses, and the Hospital for Special Surgery. Symposium attendees
      recommended ways in which nurses could take on greater leadership roles in
      research, policy, education, and clinical practice for the early diagnosis and
      management of this prevalent condition. The full report is available online at
      http://journals.lww.com/ajnonline/Pages/SOS.aspx.

PMID- 22373692
TI  - Professional development:  nurses on boards.

PMID- 22373693
TI  - Ethical issues: Putting the meds in the applesauce.

PMID- 22373694
TI  - Tea with Miss Elsie.

PMID- 22373696
TI  - Neurotransmitter vesicle release from human model neurons (NT2) is sensitive to
      botulinum toxin A.
AB  - Botulinum neurotoxins (BoNTs) internalize into nerve terminals and block the
      release of neurotransmitters into the synapse. BoNTs are widely used as a
      therapeutic agent for treatment of movement disorders and recently gained more
      attention as a biological weapon. Consequently, there is strong interest to
      develop a cell-based assay platform to screen the toxicity and bioactivity of the
      BoNTs. In this study, we present an in vitro screening assay for BoNT/A based on
      differentiated human embryonal carcinoma stem (NT2) cells. The human NT2 cells
      fully differentiated into mature neurons that display immunoreactivity to
      cytoskeletal markers (betaIII-tubulin and MAP2) and presynaptic proteins
      (synapsin and synaptotagmin I). We showed that the human NT2 cells undergo a
      process of exo-endocytotic synaptic vesicle recycling upon depolarization with
      high K(+) buffer. By employing an antibody directed against light chain of
      BoNT/A, we detected internalized toxin as a punctate staining along the neurites
      of the NT2 neurons. Using well-established methods of synaptic vesicle exocytosis
      assay (luminal synaptotagmin I and FM1-43 imaging) we show that pre-incubation
      with BoNT/A resulted in a blockade of vesicle release from human NT2 neurons in a
      dose-dependent manner. Moreover, this blocking effect of BoNT/A was abolished by
      pre-adsorbing the toxin with neutralizing antibody. In a proof of principle, we
      demonstrate that our cell culture assay for vesicle release is sensitive to
      BoNT/A and the activity of BoNT/A can be blocked by specific neutralizing
      antibodies. Overall our data suggest that human NT2 neurons are suitable for
      large scale screening of botulinum bioactivity.

PMID- 22373697
TI  - Calreticulin signaling in health and disease.
AB  - Calreticulin is an endoplasmic reticulum Ca(2+) binding chaperone that has
      multiple functions inside and outside of the endoplasmic reticulum. It is
      involved in the quality control of newly synthesized proteins and glycoproteins,
      interacting with various other endoplasmic reticulum chaperones, specifically
      calnexin and ER protein of 57-kDa in the calreticulin/calnexin cycle.
      Calreticulin also plays a crucial role in regulating intracellular Ca(2+)
      homeostasis, associating calreticulin with a wide variety of signaling processes,
      such as cardiogenesis, adipocyte differentiation and cellular stress responses.
      The role of calreticulin outside of the endoplasmic reticulum is also extensive,
      including functions in wound healing and immunity. Therefore, calreticulin has
      important implications in health and disease. Signaling facts.

PMID- 22373695
TI  - Anticonvulsant and antioxidant effects of cyano-carvone and its action on
      acetylcholinesterase activity in mice hippocampus.
AB  - The anticonvulsant effect of cyano-carvone, a monoterpene monocyclic, was
      investigated in epilepsy model induced by pilocarpine. Cyano-carvone at doses of
      25, 50 or 75 mg/kg promoted a reduction of 16.7, 33 and 66.7%, respectively,
      against pilocarpine-induced seizures, and it was efficacious in increasing both
      the latency to first seizures and the survival percentage, resulting in 33.3, 67
      and 91.7% of protection against death induced by seizures, respectively (P <
      0.05). The reference drug atropine (25 mg/kg) also produced a significant
      protection (100%). Its monoterpene, at 25, 50 and 75 mg/kg, was also capable to
      increase the latency for installation of status epilepticus induced by
      pilocarpine, and presented a significant protection against lipid peroxidation
      and nitrite formation in mice hippocampus (P < 0.05). In addition, it was
      observed that the cyano-carvone pretreatment increased the acetylcholinesterase
      activity in mice hippocampus after pilocarpine-induced seizures. The present
      results clearly indicate the anticonvulsant ability of cyano-carvone, which can
      be, at least in part, explained by the increased activity of the
      acetylcholinesterase enzyme. Our data suggest that the action mechanism can also
      be due to a direct activation of the antioxidant enzymes that could be associated
      with a reduction observed in oxidative stress in mice hippocampus, probably
      involving an inhibition of free radical production.

PMID- 22373698
TI  - Nephrectomy as a cause of chronic kidney disease in the treatment of
      urolithiasis: a case-control study.
AB  - OBJECTIVE: To analyze the clinical course of nephrectomized patients due to
      complications related to nephrolithiasis and ascertain the prevalence of chronic
      kidney disease (CKD) in this population. METHODS: From 2005 to 2010, 658 patients
      were treated with urolithiasis. Among these, 30 (4.6%) were nephrectomized. For
      each case, a control was selected and matched to the case by age, sex and disease
      duration. All data were collected from medical records, which contained the
      clinical, laboratory evaluation and diagnostic imaging. RESULTS: Age of the study
      group was 51.5 +/- 10.4 years and the control group 47.1 +/- 5.2 years. There
      were 17 (85%) women and three men in each group. Patients from the study group
      reported 3 (range, 1-5) episodes of acute renal colic before nephrectomy. Urinary
      tract infection and hematuria was detected in 70% of cases before surgery. In
      addition, half of the patients had at least one previous urological procedure.
      The control group showed higher urinary levels of calcium (216.1 +/- 114.3 vs.
      130.9 +/- 72.2), uric acid (530.2 +/- 197.4 vs. 424 +/- 75.2) and citrate (755 +/
      533 vs. 380.2 +/- 260.7), p < 0.01, 0.03 and 0.01, respectively. The creatinine
      clearance was lower in the study group, 52.5 +/- 18.8 ml/min vs. 92.9 +/- 24.2
      ml/min in the control group (p < 0.001). CONCLUSIONS: There was a decrease in
      kidney function in nephrectomized patients compared to a control group of stone
      forming patients with both kidneys. Prospective studies are needed to assess the
      incidence of CKD in patients with nephrolithiasis submitted to nephrectomy.

PMID- 22373701
TI  - Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity,
      aristolochic acid nephropathy.
AB  - Chinese herbs nephropathy (CHN) and Balkan endemic nephropathy (BEN) are chronic
      tubulointerstitial renal diseases associated with urothelial carcinoma. The
      clinical expression and pathological lesions observed at different stages of CHN
      and BEN are strikingly similar. Both have been linked to exposure to aristolochic
      acid (AA), a powerful nephrotoxin and human carcinogen. Jelakovic et al. present
      molecular epidemiological evidence relating urothelial carcinoma in patients with
      BEN to dietary exposure to AA. It is time to abandon the terms 'CHN' and 'BEN'
      and introduce 'aristolochic acid nephropathy' to cover both clinical conditions.

PMID- 22373702
TI  - Multiple comparisons, interaction effects, and statistical inference: lessons
      from chronic kidney disease progression among blacks.
AB  - A post hoc analysis of a randomized trial comparing progression of chronic kidney
      disease among blacks and non-blacks provides an opportunity to explore
      statistical inference. Multiple comparisons without penalizing the P-value can
      lead to false positive results; this is illustrated using simulation. Tests of
      statistical interaction are then applied and interpreted to understand effect
      modification (or lack thereof) in the context of this trial.

PMID- 22373703
TI  - Have we observed the implications of the acute fall in eGFR during treatment with
      losartan?

PMID- 22373704
TI  - Guidelines and medication compliance.

PMID- 22373705
TI  - Pre-renal success.

PMID- 22373706
TI  - Clinical pharmacists and patients with chronic kidney disease.

PMID- 22373708
TI  - Regarding 'Early postoperative serum cystatin C predicts severe acute kidney
      injury following pediatric cardiac surgery'.

PMID- 22373711
TI  - CKD-associated atherosclerosis and monocyte heterogeneity.

PMID- 22373712
TI  - MR imaging as a specific diagnostic tool for bilateral microcysts in chronic
      lithium nephropathy.

PMID- 22373713
TI  - The Case ? Hyperbicarbonatemia in a patient with Waldenstrom's macroglobulinemia.
      Pseudohyperbicarbonatemia due to paraproteinemia.

PMID- 22373714
TI  - Anticipatory anxiety as a function of panic attacks and panic-related self
      efficacy: an ambulatory assessment study in panic disorder.
AB  - BACKGROUND: Panic attacks and anticipatory anxiety are considered to be inter
      correlated, yet distinctive, features of panic disorder, both contributing to its
      onset and maintenance as well as to the associated impairment. Given the
      difficulty to yield ecologically valid data on these fluctuating symptoms the
      natural course of anticipatory anxiety and its correlates have seldom been
      addressed with adequate methods. AIMS: The current study aimed at further
      exploring the natural variance of anticipatory anxiety and its interdependence
      with panic-related variables. In addition, impact of anxiety sensitivity, and
      perceived ability to cope with panic on the relation between panic attacks and
      subsequent anxiety was inspected. METHOD: Based on an Ecological Momentary
      Assessment approach, 21 patients with panic disorder rated study variables
      continuously over one week; 549 question sets were completed. RESULTS:
      Anticipatory anxiety followed a diurnal pattern and was associated with
      situational and internal variables typically linked to panic experiences.
      Preceding panic attacks intensified anticipatory anxiety and associated negative
      emotional states; however, perceived ability to cope attenuated these effects.
      CONCLUSION: Based on natural observation data, results largely support the
      importance of cognitive appraisals for anticipatory anxiety, and its interplay
      with panic attacks as it has been suggested by cognitive theory and recent
      findings in extinction learning research.

PMID- 22373715
TI  - Clinical implications of molecular changes in pediatric Barrett's esophagus.
AB  - Barrett's esophagus (BE) is a preneoplastic condition that predisposes to
      esophageal adenocarcinoma. Although data on the occurrence of BE in children are
      limited, recent studies have suggested an increase in the pediatric population.
      BE is thought to be a complex disease in which individual genetic predisposition
      interacts with environmental stimuli. Early premalignant clones produce
      biological and genetic heterogeneity, resulting in stepwise changes in
      differentiation, proliferation, and apoptosis, allowing disease progression under
      selective pressure. The value of endoscopic surveillance biopsy for dysplasia and
      carcinoma in patients with BE is controversial. Thus, the recognition of early
      and objective alternative risk markers, less susceptible of sampling error, will
      be of relevance in the management of BE patients. The possibility of performing
      molecular genetics on paraffin-embedded biopsies will expand our understanding of
      the natural history of BE and may lead to the use of biomarkers to inform
      treatment strategies.

PMID- 22373716
TI  - Positional requirements for the stimulation of mRNA nuclear export by ALREX
      promoting elements.
AB  - The majority of vertebrate mRNAs that encode secreted, membrane-bound or
      mitochondrial proteins contain elements at the 5' end of the ORF that activate an
      alternative mRNA nuclear export (ALREX) pathway. Here we demonstrate that these
      elements promote efficient export and proper cytoplasmic localization only when
      they are found at the 5' end of the transcript.

PMID- 22373717
TI  - Occipital lobe epilepsy with fear as leading ictal symptom.
AB  - Ictal fear is a semiological feature which is commonly associated with mesial
      temporal lobe epilepsy. Here, we describe fear as a leading symptom in
      cryptogenic occipital lobe epilepsy. In a patient with negative MRI findings,
      intracranial EEG recordings documented a strict correlation between habitual
      ictal anxiety attacks and both spontaneous and stimulation-induced epileptic
      activity in a right occipital epileptogenic area with subsequent spreading to the
      symptomatogenic zone in the amygdala. Circumscribed occipital topectomy led to
      seizure freedom. Episodes of non-epileptic fear ceased shortly afterwards. This
      report provides insight into pathways of propagation of epileptic activity,
      illustrates different etiologies of pathologic fear and underlines the importance
      of ictal EEG recordings.

PMID- 22373718
TI  - Underdrive pacing to terminate ventricular tachycardia.

PMID- 22373719
TI  - An active solution to a slippery problem: implanting CRT-D via a persistent left
      SVC.

PMID- 22373721
TI  - Severe pulmonary regurgitation after tetralogy-of-Fallot repair: transcatheter
      treatment with the Edwards SAPIEN XT heart valve.

PMID- 22373722
TI  - Role of vitamin D deficiency in cardiovascular disease.
AB  - Vitamin D is a fat-soluble secosteroid produced in the skin as a result of
      sunlight exposure, and its circulating levels are reduced in a wide variety of
      chronic illnesses and obesity. Observational studies clearly demonstrate a higher
      incidence of cardiovascular events in individuals with low circulating 25
      hydroxyvitamin D [25(OH)D]. This relationship can potentially be explained by
      confounding, because individuals with low 25(OH)D are generally older, frailer,
      heavier, and have more comorbidities and higher estimated cardiovascular risk
      than individuals with higher 25(OH)D. The vitamin D receptor appears to be widely
      distributed, including in cardiovascular tissue, although this has recently been
      contested. Despite these epidemiological and laboratory findings, meta-analyses
      of clinical trials have not shown evidence of beneficial effects of vitamin D
      supplementation on cardiovascular endpoints. Trials are underway to assess these
      possibilities further. At present, there is insufficient evidence to support
      vitamin D supplementation for improving cardiovascular outcomes.

PMID- 22373720
TI  - Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation
      acute coronary syndromes.
AB  - OBJECTIVE: To assess the relationship between osteoprotegerin (OPG) and
      cardiovascular death, and the pathobiological mechanisms contributing to the
      association, in acute coronary syndromes (ACS). DESIGN: Prospective
      observational. SETTING: Biomarker substudy of MERLIN-TIMI 36, a randomised,
      placebo controlled trial of ranolazine in non-ST elevation (NSTE)-ACS. PATIENTS:
      4463 patients with NSTE-ACS. INTERVENTIONS: Ranolazine or placebo. MAIN OUTCOME
      MEASURES: Incidence of cardiovascular death (CV death); additionally, heart
      failure (HF), cardiac arrhythmias, in-hospital ischaemia, severe recurrent
      ischaemia or recurrent myocardial infarction (MI). RESULTS: During a median
      follow-up of 341 days, 208 patients died of cardiovascular causes. The OPG
      baseline concentration was strongly associated with both 30 day and 1 year
      incidence of CV death. After adjustment for conventional risk markers, OPG
      concentrations (log transformed) remained a significant predictor of CV death by
      30 days (HR (95% CI) 2.32 (1.30 to 4.17); p=0.005) and by 1 year (HR 1.85 (1.33
      to 2.59); p<0.001). Baseline levels of OPG were also an independent predictor of
      new or worsening HF at 30 days (HR 2.25 (1.38 to 3.69); p=0.001) and 1 year (HR
      1.81 (1.26 to 2.58) p=0.001). By univariable analysis, higher OPG was associated
      with both early ischaemic and arrhythmic events. Although OPG levels were
      associated with recurrent MI within 12 months, this association was attenuated
      and no longer significant after multivariable adjustment. CONCLUSIONS: OPG is
      independently associated with 30 day and 1 year risk of cardiovascular mortality
      and HF development after NSTE-ACS. As no independent relationship between OPG
      levels and recurrent ischaemia or MI was observed, myocardial dysfunction may be
      a more important stimulus for OPG production than ischaemia in ACS.

PMID- 22373723
TI  - Protein inference: a review.
AB  - Assembling peptides identified from tandem mass spectra into a list of proteins,
      referred to as protein inference, is a critical step in proteomics research. Due
      to the existence of degenerate peptides and 'one-hit wonders', it is very
      difficult to determine which proteins are present in the sample. In this paper,
      we review existing protein inference methods and classify them according to the
      source of peptide identifications and the principle of algorithms. It is hoped
      that the readers will gain a good understanding of the current development in
      this field after reading this review and come up with new protein inference
      algorithms.

PMID- 22373725
TI  - Degree of portal vein thrombosis might be associated with recanalization during
      anticoagulation.

PMID- 22373724
TI  - Etiologies and outcomes of acute liver failure in Germany.
AB  - BACKGROUND & AIMS: Acute liver failure (ALF) is a severe form of acute liver
      injury that can progress to multiple organ failure. We investigated causes and
      outcomes of ALF. METHODS: Eleven university medical centers in Germany were asked
      to report patients with (primary) severe acute liver injury (sALI) (international
      normalized ratio [INR] >1.5 but no hepatic encephalopathy) and primary ALF (INR
      >1.5 with overt hepatic encephalopathy) treated from 2008 to 2009. Data were
      analyzed from 46 patients with sALI and 109 patients with ALF. RESULTS: The most
      frequent etiologies of primary ALF were non-acetaminophen drug-induced (32%),
      indeterminate (24%), and viral (21%); acetaminophen ingestion was the cause of
      ALF in only 9% of patients. The support of a ventilator was required by 44% of
      patients with ALF, vasopressors by 38%, and renal replacement by 36%. Seventy
      nine patients with ALF (72%) survived until hospital discharge, 38 (35%) survived
      without emergency liver transplantation (ELT), and 51 received ELT (47%); 80% of
      patients who received ELT survived until discharge from the hospital.
      CONCLUSIONS: In Germany, drug toxicity, indeterminate etiology, and viral
      hepatitis appear to be the major causes of primary ALF, which has high mortality.
      Patients with ALF are at great risk of progressing to multiple organ failure, but
      80% of patients who receive ELT survive until discharge from the hospital.

PMID- 22373726
TI  - Increased risk of miscarriage and ectopic pregnancy among women with irritable
      bowel syndrome.
AB  - BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most commonly diagnosed
      gastrointestinal condition and is most prevalent in women of reproductive age. We
      investigated the effects of IBS on risk for adverse outcomes from pregnancy.
      METHODS: We conducted a cohort study by using the United Kingdom General Practice
      Research Database. The study cohort consisted of 100,000 women selected by
      stratified random sampling from all women with a diagnosis of pregnancy from
      January 1, 1990, to December 31, 2008. Those with a recorded diagnosis of IBS
      before pregnancy were identified (n = 26,543). Outcome measures were spontaneous
      miscarriage, ectopic pregnancy, preeclampsia, and stillbirth. Odds ratios (ORs)
      and 95% confidence intervals (CIs) for the association between IBS and pregnancy
      outcomes were estimated by using logistic regression adjusted for several
      potential confounders. RESULTS: Of women diagnosed with IBS before pregnancy,
      6578 (7%) had a spontaneous miscarriage, 741 (0.74%) had an ectopic pregnancy,
      425 (0.43%) developed preeclampsia, and 217 (0.22%) had a stillbirth. Maternal
      IBS was associated with a moderately increased risk of miscarriage (OR, 1.21; 95%
      CI, 1.13-1.30) and ectopic pregnancy (OR, 1.28%; 95% CI, 1.06-1.55). There did
      not appear to be an association between IBS and preeclampsia (OR, 1.09; 95% CI,
      0.85-1.39) or stillbirth (OR, 1.00; 95% CI, 0.69-1.44). CONCLUSIONS: IBS, a
      common disorder in women of reproductive age, appears to increase the risk of
      miscarriage and ectopic pregnancy. These findings indicate the importance of
      prenatal care for women with IBS.

PMID- 22373727
TI  - The variable presentations and broadening geographic distribution of hepatic
      fascioliasis.
AB  - We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the
      United States from Africa and the Middle East. The first case presented with
      acute infection. Prominent clinical features included abdominal pain, elevated
      liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and
      marked peripheral eosinophilia. The second case was diagnosed in the chronic
      stage of infection and presented with right upper quadrant abdominal pain, cystic
      hepatic lesions, and an adult fluke in the common bile duct. We review the life
      cycle of Fasciola species, the corresponding clinical features during the stages
      of human infection, diagnostic methods, and the evolving understanding of the
      epidemiology of human fascioliasis, particularly emphasizing fascioliasis in
      African countries.

PMID- 22373728
TI  - The future of falls research: nurses should lead the way.

PMID- 22373729
TI  - Falls and fall-related injuries associated with function-focused care.
AB  - The purpose of this study was to describe falls and injuries within assisted
      living (AL) communities and determine whether a function-focused care (FFC)
      intervention increased the risk of falls and/or injuries. This was a secondary
      data analysis using data from a 12-month cluster-randomized controlled trial in
      which four AL communities were matched based on ownership and randomly assigned
      to treatment (FFC-AL) or attention control (FFC--education only). Demographic
      information and information on comorbidities, falls, and consequences postfall,
      ability to ambulate 50 yards, gait and balance, cognition, person-environment
      fit, and medication use were collected. Logistic regression was used to test the
      hypotheses. Exposure to FFC-AL did not result in an increased likelihood of
      falling (Wald = 0.01, p = .96) or sustaining an injury (B = 0.42, Wald = 0.88, p
      = .35). The study findings supported prior research findings supporting the
      safety of interventions that optimize function and encourage physical activity
      among older adults.

PMID- 22373730
TI  - Orthostatic hypotension in older nursing home residents who fall: are they dizzy?
AB  - Orthostatic hypotension (OH) and dizziness have been linked to older adult falls.
      As a treatable condition, the detection of OH is of clinical importance to falls
      prevention. Gaps in the literature about symptoms associated with OH among older
      adult fallers, such as dizziness led to this secondary analysis of blood pressure
      data and reported symptoms. Of the 194 Registered Nurse (RN) documented falls,
      most (n = 91; 46.9%) failed to meet the prevailing diagnostic criteria for OH; 18
      (9.2%) met criteria; and 8 (4%) nearly met the OH criteria. OH determinations
      were incomplete or absent in 41% (n = 77). Of the 18 residents with OH, none
      reported dizziness, instead half reported loss of balance. We conclude, older
      residents did not report symptoms of dizziness prior to OH drops in blood
      pressure and falls. Further study is warranted to identify other predictive
      symptoms of OH and to evaluate nursing staff's understanding of OH.

PMID- 22373731
TI  - Analysis of measurement tools of fear of falling for high-risk, community
      dwelling older adults.
AB  - Fear of falling has many health consequences among older adults and may lead to
      curtailment of activities, immobility, functional dependence, falls, and serious
      injury. The lack of clarity as to how to best measure fear of falling among high
      risk, community-dwelling older adults defined as those who are nursing home
      eligible, functionally dependent, and vulnerable is further complicated by the
      multiple definitions used throughout the science. Fear of falling is important to
      measure effectively if we are to develop and test interventions to promote safe
      aging in place and prevent injury and institutionalization. This integrative
      review, 1982 to the present, leads to the conclusion that the Falls Efficacy
      Scale-International (FES-I) long form stands out as the most appropriate
      measurement tool to best assess fear of falling in this unique, understudied, and
      underserved population.

PMID- 22373732
TI  - Prospects for a statistical theory of LC/TOFMS data.
AB  - The critical importance of employing sound statistical arguments when seeking to
      draw inferences from inexact measurements is well-established throughout the
      sciences. Yet fundamental statistical methods such as hypothesis testing can
      currently be applied to only a small subset of the data analytical problems
      encountered in LC/MS experiments. The means of inference that are more generally
      employed are based on a variety of heuristic techniques and a largely qualitative
      understanding of their behavior. In this article, we attempt to move towards a
      more formalized approach to the analysis of LC/TOFMS data by establishing some of
      the core concepts required for a detailed mathematical description of the data.
      Using arguments that are based on the fundamental workings of the instrument, we
      derive and validate a probability distribution that approximates that of the
      empirically obtained data and on the basis of which formal statistical tests can
      be constructed. Unlike many existing statistical models for MS data, the one
      presented here aims for rigor rather than generality. Consequently, the model is
      closely tailored to a particular type of TOF mass spectrometer although the
      general approach carries over to other instrument designs. Looking ahead, we
      argue that further improvements in our ability to characterize the data
      mathematically could enable us to address a wide range of data analytical
      problems in a statistically rigorous manner.

PMID- 22373733
TI  - Regioselective synthesis and antimicrobial activities of some novel aryloxyacetic
      acid derivatives.
AB  - Reaction of aryloxyacetic acid hydrazides 1a,b with alpha-haloketones such as
      hydrazonoyl chlorides 2a,b; phenacyl bromides 6a,b; and 2-chloro-N-(1,3-thiazol-2
      yl)acetamide 10 led to the formation N-(4-halophenyl)-2-[2
      (aryloxyacetyl)hydrazinylidene]propanehydrazonoyl chloride 3a-d; (ethene-1,2
      diyl)bis-2-(naphthalen-2-yloxy)acetohydrazides 9a,b; and 2-[(2
      aryloxyacetyl)hydrazinyl)]-N-(1,3-thiazol-2-yl)acetamides 11a,b; respectively.
      The nucleophilic substitution reaction of 3a-d with thiophenol and sodium
      benzenesulfinate furnished the corresponding
      hydrazinylidenepropanehydrazonothioates 4a-d and sulfones 5a-d, respectively. The
      antimicrobial activities of the synthesized compounds were evaluated. The
      obtained data indicated that the majority of the tested compounds exhibited
      antibacterial activity while all those compounds showed antifungal activity.
      Sulfone 5d showed greater effect with all tested organism than well known
      antibacterial and antifungal agents with minimal inhibitory concentration (MIC)
      ranged between 4.125 and 16.5 MUg/mL.

PMID- 22373734
TI  - Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure
      activity relationship for anti-inflammatory drug.
AB  - Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG)
      production cascades in the human body. The mechanisms of both the anti
      inflammation effects and the side-effects of traditional COX inhibitors are
      associated with the existence of two COX isoforms. Thus while COX-1 is
      predominantly expressed ubiquitously and constitutively, and it serves a
      housekeeping role in processes such as gastrointestinal (GI) mucosa protection,
      COX-2 is absent or exhibits a low level of expression in most tissues, and is
      highly upregulated in response to endotoxin, virus, inflammatory or tissue-injury
      stimuli/signals, and tumour promoter in the various types of organs, tissues, and
      cells. Furthermore, COX-2 contribution to PGE(2) and PGI(2) production evokes and
      sustains systemic or peripheral inflammatory disease, but it is not involved in
      the COX-1-mediated GI tract events. Also, hypersensitivity of aspirin owing to
      its inhibitory action against COX-1 is a significant concern clinically.
      Consequently, highly selective COX-2 inhibitors have been needed for the
      treatment of inflammatory- and inflammation related-diseases that include
      pyrexia, inflammation, pain, rheumatoid arthritis, osteoarthritis, and cancers.
      In this study, a series of novel [2-{[(4-substituted or 4,5-disubstituted)
      pyridin-2-yl]carbonyl}-(5- or 6-substituted or 5,6-disubstituted)-1H-indol-3
      yl]acetic acid analogues was designed, synthesized, and evaluated to identify
      potent and selective COX-2 inhibitors as potential agents against inflammatory
      diseases. As significant findings, the present study clarified unique structure
      activity relationship of the analogues toward potent and selective COX-2
      inhibition in vitro, and identified 2-{6-fluoro-2-[4-methyl-2-pridinyl)carbonyl]
      1H-indol-3-yl}acetic acid as a potent and selective COX-2 inhibitor in vitro that
      demonstrated orally potent anti-inflammation efficacy against carrageenan-induced
      oedema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation
      model in vivo.

PMID- 22373735
TI  - The selective cytotoxic activity in breast cancer cells by an anthranilic alcohol
      derived acyclic 5-fluorouracil O,N-acetal is mediated by endoplasmic reticulum
      stress-induced apoptosis.
AB  - Advance in the knowledge of molecular biology has thrown light on many aspects of
      apoptosis regulation mechanisms. This has allowed a change in anti-cancer therapy
      trends, from classic cytotoxic strategies to the development of new non-harmful
      therapies which target the apoptosis response selectively only in tumour cells.
      We have selected an anthranilic alcohol-derived acyclic 5-fluorouracil O,N-acetal
      (5) to carry out the anti-cancer studies. This compound shows activity as a
      potent growth inhibitor of the tumour cell line MCF-7 at a very low
      concentration. Moreover, when this compound was administered to the non
      neoplastic cell line, MCF-10A displayed less toxicity resulting in lower rates of
      apoptosis. Further studies by microarray hybridization, real-time PCR and western
      blot showed that when administered to human breast cancer cells, MCF-7, 5 had no
      activity against classic pro-apoptotic genes such as p53, and even induced the
      down-regulation of anti-apoptotic genes such as Bcl-2. In contrast, several pro
      apoptotic genes related with the endoplasmic reticulum (ER)-stress-induced
      apoptosis, such as BBC3 and Noxa, appeared up-regulated. These results seem to
      show that the mechanism of action and selectivity of 5 was via the activation of
      the ER stress-induced apoptosis. The selective activity of this compound against
      tumour cells via the ER stress-induced apoptosis supposes a great advantage for
      future therapeutic use.

PMID- 22373740
TI  - Osteoarthritis: the patient's experience.

PMID- 22373736
TI  - Heat stress and the photosynthetic electron transport chain of the lichen
      Parmelina tiliacea (Hoffm.) Ach. in the dry and the wet state: differences and
      similarities with the heat stress response of higher plants.
AB  - Thalli of the foliose lichen species Parmelina tiliacea were studied to determine
      responses of the photosynthetic apparatus to high temperatures in the dry and wet
      state. The speed with which dry thalli were activated by water following a 24 h
      exposure at different temperatures decreased as the temperature was increased.
      But even following a 24 h exposure to 50  degrees C the fluorescence induction
      kinetics OJIP reflecting the reduction kinetics of the photosynthetic electron
      transport chain had completely recovered within 128 min. Exposure of dry thalli
      to 50  degrees C for 24 h did not induce a K-peak in the fluorescence rise
      suggesting that the oxygen evolving complex had remained intact. This contrasted
      strongly with wet thalli were submergence for 40 s in water of 45  degrees C
      inactivated most of the photosystem II reaction centres. In wet thalli, following
      the destruction of the Mn-cluster, the donation rate to photosystem II by
      alternative donors (e.g. ascorbate) was lower than in higher plants. This is
      associated with the near absence of a secondary rise peak (~1 s) normally
      observed in higher plants. Analysing the 820 nm and prompt fluorescence
      transients suggested that the M-peak (occurs around 2-5 s) in heat-treated wet
      lichen thalli is related to cyclic electron transport around photosystem I.
      Normally, heat stress in lichen thalli leads to desiccation and as consequence
      lichens may lack the heat-stress-tolerance-increasing mechanisms observed in
      higher plants. Wet lichen thalli may, therefore, represent an attractive
      reference system for the evaluation of processes related with heat stress in
      higher plants.

PMID- 22373741
TI  - The impact of osteoarthritis in the United States:  a population-health
      perspective.
AB  - Arthritis, of which osteoarthritis (OA) is the most common type, is the most
      frequent cause of disability among adults in the United States. The authors
      reviewed the epidemiologic literature to identify studies that describe the
      population-based burden of OA-that is, the burden in all adults in the community.
      They found that 27 million adults-more than 10% of the U.S. adult population-had
      clinical OA in 2005, and in 2009 OA was the fourth most common cause of
      hospitalization. OA is the leading indication for joint replacement surgery;
      905,000 knee and hip replacements were performed in 2009 at a cost of $42.3
      billion. Obesity is a strong risk factor for OA of the knee and hip. Nurses can
      improve the quality of life of people with OA by raising awareness among their
      patients and peers of the substantial OA burden and the strategies, such as
      physical activity, that can reduce it.

PMID- 22373742
TI  - Making osteoarthritis a public health priority.
AB  - National, state, and local policymakers and society at large are paying growing
      attention to osteoarthritis. This movement is fueled by organizations and
      coalitions that are championing important initiatives. This article spotlights
      several initiatives sponsored by the Arthritis Foundation and other
      organizations.

PMID- 22373743
TI  - Assessing for risk and progression of osteoarthritis: the nurse's role.
AB  - The authors review the primary and secondary risk factors for osteoarthritis
      (OA), its pathophysiology and epidemiology, the evidence-based approaches to
      slowing progression, and the role of nurses encountering OA in primary care and
      other settings.

PMID- 22373744
TI  - The state of the science in the prevention and management of osteoarthritis.
AB  - In July 2011 a symposium on osteoarthritis convened experts in many areas
      nursing, epidemiology, rheumatology, public policy, geriatrics, pharmacotherapy,
      physical therapy, and complementary modalities-to discuss the importance of
      nurses in reducing the disability caused by osteoarthritis. The planning
      committee included representatives from AJN, the National Association of
      Orthopaedic Nurses, and the Hospital for Special Surgery. Symposium attendees
      recommended ways in which nurses could take on greater leadership roles in
      research, policy, education, and clinical practice for the early diagnosis and
      management of this prevalent condition. The full report is available online at
      http://journals.lww.com/ajnonline/Pages/SOS.aspx.

PMID- 22373745
TI  - Rehabilitation interventions for pain and disability in osteoarthritis.
AB  - Osteoarthritis (OA) results in progressive destruction of articular cartilage and
      bone at the joint margins, leading to impairments extending far beyond the
      synovial joint. Rehabilitation interventions that target specific impairments and
      activity restrictions can help restore independence and promote healthy living.
      Such interventions include exercise, physical modalities (ice, heat,
      ultrasonography), manual techniques (mobilization and manipulation), and
      assistive devices. The predominance of evidence on the effects of rehabilitation
      interventions for knee and hip OA suggest that they afford modest pain relief,
      reduced disability, and improved function. Research is needed to identify the
      modes of exercise and the effective doses for relief of symptoms and functional
      limitations.

PMID- 22373746
TI  - Pharmacologic management of osteoarthritis-related pain in older adults.
AB  - OVERVIEW: Because pain is a common and debilitating symptom of osteoarthritis in
      older adults, the authors reviewed data on the efficacy and safety of commonly
      used oral, topical, and intraarticular drug therapies in this population. A
      search of several databases found that most studies have focused on knee
      osteoarthritis and reported only short-term outcomes. Also, treatment efficacy
      was found to vary by drug class; the smallest effect was observed with
      acetaminophen and the largest with opioids and viscosupplements. Acetaminophen
      and topical agents had the best safety profiles, whereas oral nonsteroidal
      antiinflammatory drugs and opioids had the worst. Little data were available on
      patients ages 75 years old and older and on patients from diverse racial and
      ethnic groups. Most drug therapies gave mild-to-moderate pain relief; their long
      term safety and efficacy and their effects in diverse populations (particularly
      older adults) remain undetermined.

PMID- 22373747
TI  - Complementary and alternative modalities to relieve osteoarthritis symptoms.
AB  - Conventional medical treatment of osteoarthritis often successfully relieves pain
      but can also produce adverse gastrointestinal and cardiovascular effects,
      especially with long-term use. Hence, many patients use complementary and
      alternative medicine (CAM) to prevent, control, and manage the pain of
      osteoarthritis. The author reviews the evidence on the efficacy and safety of
      several CAM therapies often used for osteoarthritis management, including mind
      body therapies, supplements, and body-based treatments.

PMID- 22373748
TI  - Panel discussion:  issues and strategies for nurses caring for adults with
      osteoarthritis.

PMID- 22373749
TI  - Strategies to support self-management in osteoarthritis.
AB  - This overview of successful strategies for supporting self-management in patients
      with osteoarthritis (OA) defines the concepts of self-management, self-management
      support (SMS), and self-management education (SME); describes five categories of
      SMS interventions; identifies common elements across SMS categories; and provides
      evidence for and examples of self-management tools that are useful in OA. SMS
      categories include SME, other skill-building and behavior-change interventions,
      supportive provider interactions, ongoing supportive follow-up, and environmental
      changes. Where available, relevant OA-specific SMS strategies are used to
      illustrate these categories.

PMID- 22373752
TI  - Residencies in Neuropsychiatry. KA Menninger (1937). Reprinted from the J Nerv
      Ment Dis. 86(2): 245.

PMID- 22373753
TI  - Neuropsychiatry: a challenge for the Journal of Nervous and Mental Disease
      (JNMD).

PMID- 22373754
TI  - Neuropsychiatry: back to the future.

PMID- 22373755
TI  - Suicide attempters and repeaters: depression and coping: a prospective study of
      early adolescents followed up as young adults.
AB  - Relationships between depression and coping among nonattempters, attempters, and
      repeaters of suicidal acts were examined across adolescence. A representative
      sample of students (T1: n = 2464; mean age, 13.7 years; 50.8% female; 88.3%
      participation) was reassessed with the same questionnaire after 1 year (T2). High
      scorers on the Mood and Feelings Questionnaire were gender- and age-matched
      randomly with low and middle scorers. This subset was assessed using diagnostic
      interviews at T2 (n = 345, 94% participation) and 5 years later using the same
      interview and questionnaire (T3, n = 252; mean age, 20.0 years; 73%
      participation). The Coping Inventory for Stressful Situations measured coping as
      three stable traits. Coping changed partly with age, depression, and attempt
      status. Differences in depression emerged before coping differences and remained
      stable. Consistently, repeaters reported higher depression and lesser task
      oriented coping. Antecedent depression predicted decreased task-oriented coping
      and increased emotional coping at age 20 years.

PMID- 22373756
TI  - Management vs. interpretation: teaching residents to listen.
AB  - It is possible to teach residents to listen psychodynamically within pressured
      clinical systems that are organized around brief management interventions without
      changing the structure of the training program to create "selected psychotherapy
      cases." Two case vignettes illustrate the amount of psychodynamic data that can
      be elicited from a time-limited clinical assessment. Focusing on the
      psychodynamics of social systems and the subtle ways in which patients and
      clinicians become involved with each other during assessment meetings can allow
      trainees to grasp unconscious functioning, projective identification,
      transference/countertransference, and interpretation. This perspective opens a
      way of thinking that illuminates the patient's struggles, reduces the need for
      management by helping the patient take charge of his or her treatment, and opens
      possibilities for both patient and trainee to improve their capacity to listen,
      both to themselves and to the human systems that surround them.

PMID- 22373757
TI  - Intolerance of uncertainty, hypochondriacal concerns, obsessive-compulsive
      symptoms, and worry.
AB  - Intolerance of uncertainty (IU) has been found to be involved in several anxiety
      disorders, including generalized anxiety disorder and obsessive-compulsive
      disorder (OCD). Few studies have examined the role of IU in health anxiety
      (HA)/hypochondriacal concerns (HC). We conducted two studies exploring the
      associations between IU and HA/HC. The first study included undergraduates (n =
      114) and indicated an association between IU and several HA/HC indices. When
      controlling for neuroticism, worry about illness was the single index of HA/HC
      that remained associated with IU. In the second study among bereaved adults (n =
      126), IU was associated with one index of HA/HC but not when neuroticism and
      anxiety sensitivity were controlled. In both studies, IU was found to be more
      strongly associated with OCD symptoms and worry than with HA/HC.

PMID- 22373758
TI  - A prospective investigation of work and nonvocational outcomes in adults with
      severe mental illness.
AB  - This study assessed the impact of steady competitive or noncompetitive employment
      on nonvocational outcomes for clients with severe mental illness receiving
      employment services. We conducted a secondary analysis of 2-year data for 187
      clients participating in a randomized controlled trial comparing two employment
      programs. Participants were classified according to 2-year employment outcomes
      into four groups: steady competitive work, steady noncompetitive work, minimal
      work, and no work. We compared these groups on 2-year outcomes including
      symptoms, hospitalizations, quality of life, and social networks. During follow
      up, working clients had fewer days of hospitalization than the no-work group. The
      steady competitive group had greater reduction in negative symptoms than did the
      no-work group. The steady noncompetitive group showed greater improvement in
      social networks compared with the other groups. Extended periods of work are
      associated with improvements in nonvocational outcomes. Beneficial effects may
      vary according to the type of employment.

PMID- 22373759
TI  - Women respond more favorably to transference intervention than men: a randomized
      study of long-term effects.
AB  - The present study focuses on whether there is a sustained difference in treatment
      response to transference interventions between women and men. Data from the First
      Experimental Study of Transference Interpretations were used. One hundred
      patients were randomized to receive dynamic psychotherapy in 1 year with either a
      moderate level of transference intervention or no transference intervention.
      Follow-ups were 1 year and 3 years after treatment termination. The two primary
      outcome measures were the Psychodynamic Functioning Scales (PFS) and Inventory of
      Interpersonal Problems-Circumplex Version. Change was assessed using linear mixed
      models. In the moderator analyses, using the primary outcome measure (PFS) and
      controlling for the effect of the level of relational functioning (Quality of
      Object Relations Scale), women and men differed significantly in their response
      to transference intervention. The average relational functioning female patients
      showed a significant positive long-term effect of transference intervention.

PMID- 22373760
TI  - Introduction:  case studies in the ethics of mental health research.
AB  - This collection presents six case studies on the ethics of mental health
      research, written by scientific researchers and ethicists from around the world.
      We publish them here as a resource for teachers of research ethics and as a
      contribution to several ongoing ethical debates. Each consists of a description
      of a research study that was proposed or carried out and an in-depth analysis of
      the ethics of the study.

PMID- 22373761
TI  - Ethical issues in a study of bipolar disorder and HIV risk among African-American
      men who have sex with men: case study in the ethics of mental health research.
AB  - African-American men who have sex with men (MSM) are at increased risk of HIV
      infection, as are individuals with severe mental illness. This study was
      conducted at the behest of members of the African-American MSM community in
      Cleveland, Ohio, to assess the co-occurrence of HIV risk and bipolar disorder
      among African-American MSM. A sample of 125 participants was recruited via flyers
      and word of mouth at venues used by members of this community. Individuals were
      assessed for HIV risk and severe mental illness. Various ethical issues were
      presented, including participant capacity and voluntariness and the risk-benefit
      ratio. Divergent perspectives of the local institutional review board and the
      community advisory group with respect to the risks and benefits of participation
      required reconciliation before the study could proceed. Solutions for the
      resolution of such conflicts are discussed.

PMID- 22373762
TI  - Institutional review boards need to increase their understanding of community
      based participatory research: commentary on a case study in the ethics of mental
      health research.

PMID- 22373763
TI  - The Bucharest Early Intervention Project: case study in the ethics of mental
      health research.
AB  - The Bucharest Early Intervention Project is the first ever randomized controlled
      trial of foster care as an alternative to institutional care for young abandoned
      children. This article examines ethical issues in the conceptualization and
      implementation of the study, which involved American investigators conducting
      research in another country, as well as vulnerable participants. We organize the
      discussion of ethical questions about the study around several key issues. These
      include the nature and location of the vulnerable study population, the social
      value of conducting the study, the risks and benefits to participants of
      participating in the study, and posttrial obligations of the investigators. In
      discussing how these questions were addressed as the study was designed and after
      it was initiated, we describe our attempts to wed sound scientific practices with
      meaningful ethical protections for participants.

PMID- 22373764
TI  - When is research socially valuable? Lessons from the Bucharest Early Intervention
      Project: commentary on a case study in the ethics of mental health research.

PMID- 22373765
TI  - Ethical and legal issues regarding consent in research with adult stroke
      patients: case study in the ethics of mental health research.
AB  - This case study describes research into interventions to enhance stroke patients'
      ability to communicate. Because patients' cognitive abilities are compromised, it
      is argued that they may lack the capacity to consent and that surrogate consent
      should be required. In South Africa, this would make conducting the research
      difficult because only court-appointed curators are "legally appropriate"
      substitutes for research enrolment. Here, the research ethics committee must
      balance legal requirements and ethical concerns. It must also balance protection
      and respect for autonomy, even for cognitively compromised participants. First,
      incapacity should not simply be assumed but should be individually assessed.
      However, stroke patients present a further complication for capacity assessment
      because they may retain the capacity to reason but have lost the ability to
      communicate effectively. Second, the research ethics committee must decide
      whether recruitment should be restricted or whether incapacitated participants
      may be enrolled. Given the low risk of harm, incapacitated persons could be
      enrolled by proxies.

PMID- 22373766
TI  - Ethical issues of placebo-controlled studies in depression and a randomized
      withdrawal trial in Japan: case study in the ethics of mental health research.
AB  - The use of placebo controls in psychiatric research is controversial. In this
      article, we focus on a troubling Japanese case of a randomized withdrawal trial
      of the antidepressant sertraline and analyze the ethical issues underlying it.
      First, we consider whether a placebo-controlled withdrawal trial should, in
      general, be considered more ethical than a standard placebo-controlled trial. We
      argue that the use of a placebo arm in this trial is ethically permissible but
      that there is no good reason to use a withdrawal trial design. Second, we discuss
      whether our moral evaluation of the use of placebo in this case should change
      when the special Japanese regulatory environment is taken into account. We argue
      that it should not and conclude that the use of withdrawal design in this case is
      ethically unacceptable.

PMID- 22373767
TI  - The ethics of a genetic screening study for antisocial personality disorder with
      Mesoamericans: case study in the ethics of mental health research.
AB  - This article contains an analysis of a research ethics committee's (REC) concerns
      about a study protocol involving genetic screening for antisocial personality
      disorder. The study was proposed by US university researchers and to be conducted
      with Mesoamerican populations in the United States and in their countries of
      origin. The analysis explains why the study was not considered ethical by the
      REC, pointing to issues with the choice of study population, informed consent,
      confidentiality, and posttrial obligations. Some recommendations are provided for
      ways in which the study could have been redesigned.

PMID- 22373768
TI  - The use of students as participants in a study of eating disorders in a
      developing country: case study in the ethics of mental health research.
AB  - This article describes the ethical analysis of an eating disorder study in which
      a university-based researcher in South Africa set out to establish the cross
      cultural validity of the Eating Disorders Inventory. The following ethical issues
      are considered in the analysis: study design, social value, study population,
      risks and benefits, oversight, informed consent, and posttrial obligations. The
      ethics analysis is based on an adaptation of the structured framework proposed by
      Emanuel et al. (The Oxford textbook of clinical research ethics; pp. 123-133,
      2008) for ethical research in developing countries. The analysis reveals that
      research that, on superficial analysis, seems to be low risk and
      noninterventional can result in adverse psychosocial effects and complexities for
      research participants and researchers alike. The study underlines the need for
      special ethics scrutiny of mental health-related research proposals involving
      students as research participants, especially when conducted by their own
      teachers.

PMID- 22373769
TI  - Students as participants: commentary on a case study in the ethics of mental
      health research.

PMID- 22373770
TI  - The eating disorders inventory in developing countries:  the ethics of research
      on subjects in cultural transition: commentary on a case study in the ethics of
      mental health research.

PMID- 22373771
TI  - Alexithymia in severe idiopathic scoliosis: findings from a cross-sectional study
      of adolescents who have or have not had operations.

PMID- 22373772
TI  - Bona fide or non-bona fide? Reply to Dr. Spielmans et al.

PMID- 22373775
TI  - Estimating demographic parameters using hidden process dynamic models.
AB  - Structured population models are widely used in plant and animal demographic
      studies to assess population dynamics. In matrix population models, populations
      are described with discrete classes of individuals (age, life history stage or
      size). To calibrate these models, longitudinal data are collected at the
      individual level to estimate demographic parameters. However, several sources of
      uncertainty can complicate parameter estimation, such as imperfect detection of
      individuals inherent to monitoring in the wild and uncertainty in assigning a
      state to an individual. Here, we show how recent statistical models can help
      overcome these issues. We focus on hidden process models that run two time series
      in parallel, one capturing the dynamics of the true states and the other
      consisting of observations arising from these underlying possibly unknown states.
      In a first case study, we illustrate hidden Markov models with an example of how
      to accommodate state uncertainty using Frequentist theory and maximum likelihood
      estimation. In a second case study, we illustrate state-space models with an
      example of how to estimate lifetime reproductive success despite imperfect
      detection, using a Bayesian framework and Markov Chain Monte Carlo simulation.
      Hidden process models are a promising tool as they allow population biologists to
      cope with process variation while simultaneously accounting for observation
      error.

PMID- 22373774
TI  - Cloning, tissue expression pattern and daily rhythms of Period1, Period2, and
      Clock transcripts in the flatfish Senegalese sole, Solea senegalensis.
AB  - An extensive network of endogenous oscillators governs vertebrate circadian
      rhythmicity. At the molecular level, they are composed of a set of clock genes
      that participate in transcriptional-translational feedback loops to control their
      own expression and that of downstream output genes. These clocks are synchronized
      with the environment, although entrainment by external periodic cues remains
      little explored in fish. In this work, partial cDNA sequences of clock genes
      representing both positive (Clock) and negative (Period1, Period2) elements of
      the molecular feedback loops were obtained from the nocturnal flatfish Senegalese
      sole, a relevant species for aquaculture and chronobiology. All of the above
      genes exhibited high identities with their respective teleost clock genes, and
      Per-Arnt-Sim or basic helix-loop-helix binding domains were recognized in their
      primary structure. They showed a widespread distribution through the animal body
      and some of them displayed daily mRNA rhythms in central (retina, optic tectum,
      diencephalon, and cerebellum) and peripheral (liver) tissues. These rhythms were
      most robust in retina and liver, exhibiting marked Period1 and Clock daily
      oscillations in transcript levels as revealed by ANOVA and cosinor analysis.
      Interestingly, expression profiles were inverted in retina and optic tectum
      compared to liver. Such differences suggest the existence of tissue-dependent
      zeitgebers for clock gene expression in this species (i.e., light for retina and
      optic tectum and feeding time for liver). This study provides novel insight into
      the location of the molecular clocks (central vs. peripheral) and their different
      phasing and synchronization pathways, which contributes to better understand the
      teleost circadian systems and its plasticity.

PMID- 22373776
TI  - Mechanical stress induces bone formation in the maxillary sinus in a short-term
      mouse model.
AB  - OBJECTIVES: Clinicians occasionally face the challenge of moving a tooth through
      the maxillary sinus. The objective of this study was to evaluate tissue
      remodeling during tooth movement into the maxillary sinus, more specifically as
      regards to bone formation. MATERIALS AND METHODS: The maxillary first molar of 20
      male mice was moved toward the palatal side by a nickel-titanium super elastic
      wire for 1 to 14 days, and the bone remodeling around the root was evaluated
      using histomorphometry and immunodetection of bone-restricted Ifitm-like (Bril)
      protein, a novel marker of active bone formation. RESULTS: When mechanical stress
      was applied to the tooth, the periodontal ligament on the palatal side was
      immediately compressed to approximately half of its original width by the tipping
      movement of the tooth. At the same time, osteoblasts deposited new bone on the
      wall of the maxillary sinus prior to bone resorption by osteoclasts on the
      periodontal side, as evidenced by the high level of expression of Bril at this
      site. As a result of these sequential processes, bone on the sinus side
      maintained a consistent thickness during the entire observation period. No root
      resorption was observed. CONCLUSIONS: Bone formation on the surface of the
      maxillary sinus was evoked by mechanotransduction of mechanical stress applied to
      a tooth over a 2-week period, and was induced ahead of bone resorption on the
      periodontal ligament side. CLINICAL RELEVANCE: Mechanical stress can be exploited
      to induce bone formation in the maxillary sinus so that teeth can be moved into
      the sinus without losing bone or causing root damage.

PMID- 22373777
TI  - Connective tissue graft plus resin-modified glass ionomer restoration for the
      treatment of gingival recession associated with non-carious cervical lesions:
      microbiological and immunological results.
AB  - OBJECTIVES: It was previously reported the clinical results of placing
      subgingival resin-modified glass ionomer restoration for treatment of gingival
      recession associated with non-carious cervical lesions. The aim of this study was
      to evaluate the influence of this treatment on the subgingival biofilm and
      gingival crevicular fluid (GCF) inflammatory markers. MATERIALS AND METHODS:
      Thirty-four patients presenting the combined defect were selected. The defects
      were treated with either connective tissue graft plus modified glass ionomer
      restoration (CTG+R) or with connective tissue graft only (CTG). Evaluation
      included bleeding on probing and probing depth, 5 different bacteria targets in
      the subgingival plaque assessed at baseline, 45, and 180 days post treatments,
      and 9 inflammatory mediators were also assessed in the GCF. RESULTS: The levels
      of each target bacterium were similar during the entire period of evaluation (p >
      0.05), both within and between groups. The highest levels among the studied
      species were observed for the bacterium associated with periodontal health.
      Additionally, the levels of all cyto/chemokines analyzed were not statistically
      different between groups (p > 0.05). CONCLUSION: Within the limits of the present
      study, it can be concluded that the presence of subgingival restoration may not
      interfere with the subgingival microflora and with GCF inflammatory markers
      analyzed. CLINICAL RELEVANCE: This approach usually leads to the placement of a
      subgingival restoration. There is a lack of information about the microbiological
      and immunological effects of this procedure. The results suggest that this
      combined approach may be considered as a treatment option for the lesion included
      in this study.

PMID- 22373778
TI  - Tetrahydrofuran as solvent in dental adhesives: cytotoxicity and dentin bond
      stability.
AB  - OBJECTIVES: The aim of this study was to investigate the cytotoxicity and 1-year
      dentin bond stability of solvated etch-and-rinse dental adhesives based on
      tetrahydrofuran (THF), acetone, or ethanol, containing water or not. MATERIALS
      AND METHODS: Seven primers were prepared using the following solvents: THF,
      acetone, ethanol, water, THF/water, acetone/water, and ethanol/water. Bovine
      dentin was used, and specimens for microtensile bond strength (MUTBS) test were
      prepared. Specimens were tested after storage in distilled water for 24 h or 1
      year. Cytotoxicity of the solvents was evaluated in 3T3/NIH mouse fibroblasts
      using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay after exposure for 24 h. RESULTS: No significant differences were detected
      among solvents after storage for 24 h, except for the water-based group, which
      showed the lowest MUTBS values. After storage for 1 year, the THF-based adhesive
      system resulted in more stable bonds. Yet, THF showed an intermediate
      cytotoxicity when compared with the other solvents, being less toxic than
      phosphate monomer and similar to 2-hydroxyethyl methacrylate. CONCLUSION: THF
      seems to be a suitable solvent for adhesive systems. CLINICAL RELEVANCE: THF is a
      promising solvent that can be used to improve dentin bond stability.

PMID- 22373780
TI  - Uniform and size-tunable mesoporous silica with fibrous morphology for drug
      delivery.
AB  - A family of mesoporous silica microspheres with fibrous morphology and different
      particle sizes ranging from about 400 to 900 nm has been successfully synthesized
      through a facile self-assembly process. The structural, morphological, and
      textural properties of the samples were well characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), nuclear magnetic
      resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), N(2)
      adsorption/desorption, and thermal gravimetry (TG). The results reveal that this
      silica-based mesoporous material exhibits excellent physical properties,
      including a fibrous spherical morphology, good thermal stability, large pore
      volume, high specific surface area and narrow size distribution. Additionally,
      the size and textural properties can be tuned by altering the silica
      precursor/template molar ratio. The formation and the self-assembly evolution
      process have also been proposed. The obtained materials were further used as a
      drug delivery carrier to investigate the in vitro drug release properties using
      doxorubicin (DOX) as a representative model drug. It was found that this kind of
      silica exhibits good biocompatibility and obvious sustained drug release
      properties, suggesting its potential application in biological fields.

PMID- 22373781
TI  - Unequal social engagement for older adults: constraints on choice.
AB  - Although some studies have confirmed positive associations between social
      engagement and well-being in later life, this study aimed to understand why some
      seniors cannot be engaged. The authors analyzed the lived experiences of 89
      seniors in three rural communities in Canada, from semi-structured interviews and
      using the constant comparison method. Five factors make choices for social
      engagement in later life unequal among older adults who differ by gender, class,
      age, and health status. Profound engagement in care work, compulsory altruism,
      personal resources, objectively perceived and subjectively available engagement
      opportunities, and ageist barriers around paid work constrain choices for seniors
      who lack privilege in the context of a market economy, particularly for low
      income older women. To avoid stigmatizing vulnerable older persons, societal
      barriers to meaningful activities must be addressed - for example, through
      provision of income security or by reversing inter- and intragenerational ageism
      in access to the labor market.

PMID- 22373779
TI  - Dentin infiltration ability of different classes of adhesive systems.
AB  - OBJECTIVES: This study evaluates the dentin infiltration ability of various types
      of adhesives and compares four classes of adhesive systems with regard to this
      property. The infiltration is determined quantitatively, characterized as tag
      length and ratio of infiltration, and qualitatively, characterized as
      homogeneity, regularity, and continuity of the resin tags. MATERIALS AND METHODS:
      Flat dentin surfaces from 140 halves of caries-free molars were bonded with four
      classes of adhesive systems. The adhesives (n = 20) were labeled with rhodamine B
      isothiocyanate and applied on the occlusal dentin following the manufacturer's
      recommendations and were subsequently light cured, 20 s. Then a 2-mm thick
      composite layer was applied and light cured, 20 s. The specimens were stored in
      distilled water at 37 degrees C, 24 h. Two slices were sectioned mesio-distally
      from each sample and were investigated with a confocal laser scanning microscope.
      The measurements were done at 0.5, 1.5, and 2.5 mm from the enamel-dentin
      junction. The data were analyzed by using analysis of variance and the general
      linear model. RESULTS: The class of adhesive, the composition, and the dentin
      position were significant factors affecting the investigated parameters. The use
      of etch and rinse adhesives in comparison to self-etch adhesives provided the
      formation of longer, more homogeneous, very regularly distributed but mostly
      fractured tags. CONCLUSIONS: A comparison of adhesives confirmed that etch and
      rinse systems remain better in bond infiltration. CLINICAL RELEVANCE: While the
      importance of tags formation on bonding is still controversially discussed,
      adhesive systems with a high ratio of infiltration might better protect the tooth
      against microorganism contamination.

PMID- 22373783
TI  - 'You can't turn back the clock': conceptualizing time after institutionalization.
AB  - ABSTRACTTime is a phenomenon that is often taken for granted. In gerontology,
      time is often equated with chronological or linear time, which thereby causes
      time to be defined as chronological age. With this paper, my purpose is to
      illuminate further understandings of time and how the passage of time is
      experienced in old age, particularly in the context of a move to a long-term care
      institution. Towards that end, I describe a case study of a gentleman coming to
      live in a long-term care facility. In this case study, time was perceived as an
      element outside day-to-day experience that structured daily life. Specific
      dimensions of temporality are evident, including biographical time, embodied
      time, and embedded time (including institutional time). These dimensions of time
      provide further understanding of the experiences of age and institutionalization.

PMID- 22373782
TI  - Does self-rated health predict death in older adults with depressive symptoms?
AB  - We analysed a prospective cohort study to determine (1) if self-rated health
      (SRH) predicts mortality in older adults with and without depressive symptoms,
      and (2) to determine if there is an interaction between SRH and depressive
      symptoms on mortality. We followed 1,751 community-dwelling adults aged 65 and
      older over five years. Measurements included age, gender, education, the Center
      for Epidemiological Studies-Depression (CES-D), SRH, the Modified Mini-Mental
      State Examination (3MS), and the Older Americans Resource Survey (OARS). Our
      outcome measure was time to death. Analyses were conducted in those with, and
      those without, depressive symptoms. We constructed Cox regression models with an
      interaction term for the CES-D and SRH. The hazard ratio (HR) for mortality was
      1.63 for those with depressive symptoms; it was 1.68 for those without. No
      significant interaction was found between depressive symptoms and SRH for
      mortality.

PMID- 22373784
TI  - Harmonizing data for collaborative research on aging: why should we foster such
      an agenda?

PMID- 22373786
TI  - White matter alterations in the corpus callosum of adolescents with first
      admission schizophrenia.
AB  - Several diffusion tensor imaging (DTI) studies involving adults and adolescents
      with schizophrenia have examined fractional anisotropy (FA) in the corpus
      callosum (CC) with conflicting findings. This may be due to confounding factors
      such as the chronicity of the disorder, long-term medication with psychotropics
      or methodological differences. To provide a clearer picture of early alterations,
      we examined 13 adolescents with first-admission schizophrenia and 13 healthy
      controls using a region-of-interest approach based on probabilistic voxel
      classification. We quantified FA in four subdivisions of the CC and hypothesized
      that adolescents with schizophrenia display a reduced FA in the genu associated
      with 'hypofrontality' and a reduced FA in the body of the CC linked to the
      heteromodal association cortex. Fiber integrity measurements revealed significant
      FA decreases in the genu and body of the CC in adolescents with schizophrenia
      compared to healthy controls. These findings emphasize the central role of the CC
      in even the early stages of schizophrenia and lend weight to hypotheses about
      frontal alterations and the central role of the heteromodal association cortex in
      the aetiopathogenesis of the disorder.

PMID- 22373787
TI  - Rchange: algorithms for computing energy changes of RNA secondary structures in
      response to base mutations.
AB  - MOTIVATION: Measuring the effects of base mutations is a powerful tool for
      functional and evolutionary analyses of RNA structures. To date, only a few
      methods have been developed for systematically computing the thermodynamic
      changes of RNA secondary structures in response to base mutations. RESULTS: We
      have developed algorithms for computing the changes of the ensemble free energy,
      mean energy and the thermodynamic entropy of RNA secondary structures for
      exhaustive patterns of single and double mutations. The computational
      complexities are O(NW(2)) (where N is sequence length and W is maximal base pair
      span) for single mutations and O(N(2)W(2)) for double mutations with large
      constant factors. We show that the changes are relatively insensitive to GC
      composition and the maximal span constraint. The mean free energy changes are
      bounded ~7-9 kcal/mol and depend only weakly on position if sequence lengths are
      sufficiently large. For tRNA sequences, the most stabilizing mutations come from
      the change of the 5(')-most base of the anticodon loop. We also show that most of
      the base changes in the acceptor stem destabilize the structures, indicating that
      the nucleotide sequence in the acceptor stem is highly optimized for secondary
      structure stability. We investigate the 22 tRNA genes in the human mitochondrial
      genome and show that non-pathogenic polymorphisms tend to cause smaller changes
      in thermodynamic variables than generic mutations, suggesting that a mutation
      which largely increases thermodynamic variables has higher possibility to be a
      pathogenic or lethal mutation. AVAILABILITY AND IMPLEMENTATION: The C++ source
      code of the Rchange software is available at
      http://www.ncrna.org/software/rchange/.

PMID- 22373785
TI  - Treatment of acute lymphoblastic leukemia with an rGel/BLyS fusion toxin.
AB  - Acute lymphoblastic leukemia (ALL) is the most common malignancy affecting
      children and a major cause of mortality from hematopoietic malignancies in
      adults. A substantial number of patients become drug resistant during
      chemotherapy, necessitating the development of alternative modes of treatment.
      rGel (recombinant Gelonin)/BlyS (B-lymphocyte stimulator) is a toxin-cytokine
      fusion protein used for selective killing of malignant B-cells expressing
      receptors for B-cell-activating factor (BAFF/BLyS) by receptor-targeted delivery
      of the toxin, Gelonin. Here, we demonstrate that rGel/BLyS binds to ALL cells
      expressing BAFF receptor (BAFF-R) and upon internalization, it induces apoptosis
      of these cells and causes downregulation of survival genes even in the presence
      of stromal protection. Using an immunodeficient transplant model for human ALL,
      we show that rGel/BLyS prolongs survival of both Philadelphia chromosome-positive
      and negative ALL-bearing mice. Furthermore, we used AMD3100, a CXCR4 antagonist,
      to mobilize the leukemic cells protected in the bone marrow (BM) microenvironment
      and the combination with rGel/BLyS resulted in a significant reduction of the
      tumor load in the BM and complete eradication of ALL cells from the circulation.
      Thus, a combination treatment with the B-cell-specific fusion toxin rGel/BLyS and
      the mobilizing agent AMD3100 could be an effective alternative approach to
      chemotherapy for the treatment of primary and relapsed ALL.

PMID- 22373788
TI  - [Anatomical double-bundle reconstruction of the medial patellofemoral ligament
      with a gracilis autograft].
AB  - OBJECTIVE: Elimination of patellofemoral instability by reconstruction of the
      medial patellofemoral ligament (MPFL) with a gracilis autograft. INDICATIONS:
      Recurring lateral luxation and subluxation of the patella, tibial tuberosity
      trochlear groove distance (TTTG) < 20 mm, persistent positive apprehension test
      in up to 45 degrees  of flexion, low grade trochlear dysplasia.
      CONTRAINDICATIONS: Traumatic luxation of the patella without anatomical risk
      factors, isolated treatment if TTTG  > 20 mm, and isolated treatment for high
      grade trochlear dysplasia (type B, C, D). SURGICAL TECHNIQUE: Supine postion.
      Stripping of the gracilis tendon. Drilling of two tunnels into the medial margin
      of the patella. Insertion of both tendon ends into the tunnels and fixation with
      resorbable screwlocks. Undermining of the fascia of the medial oblique vastus
      muscle and insertion of the tendon loop into the femoral point of insertion
      located at the medial epicondyle. Preparation of the femoral point of insertion
      and drilling of the femoral tunnel. Insertion of the graft into the femoral
      tunnel. Positioning of the knee in 30 degrees  of flexion. Positioning of the
      patella and fixation of the graft with a resorbable screw. POSTOPERATIVE
      MANAGEMENT: Two weeks of partial weight bearing. Knee orthesis for 6 weeks.
      Passive motion up to 60 degrees  of flexion for the first 2 weeks. Three weeks
      postoperatively unrestricted motion exercises, strengthening of the quadriceps
      muscle. Unlimited activity is possible 3 months postoperatively. RESULTS: The
      method presented in this manuscript was performed on 32 patients with recurring
      patellar luxation; 27 patients were available for clinical assessment at 1 year
      postoperatively. There were no recorded events of reluxation; the Kujala score
      increased on average from 61 points preoperatively to 93 points postoperatively.

PMID- 22373789
TI  - [Soft tissue balanced navigation of total knee arthroplasties].
AB  - OBJECTIVE: Implantation of a total knee arthroplasty with a correct mechanical
      axis, a rectangular joint gap and a reconstructed joint line by use of an
      imageless computer navigation device INDICATIONS: Symptomatic gonarthrosis if non
      operative treatment or joint preserving operations remains ineffective
      CONTRAINDICATIONS: Infections; soft tissue damage in the approach area; massive
      instability of the collateral ligaments SURGICAL TECHNIQUE: Medial parapatellar
      approach to the knee joint; diminution of the patella; fixation of the reference
      arrays in tibia and femur; registration of leg axis, ligament balance and surface
      of the knee joint by use of the navigation system; tibial resection perpendicular
      to the mechanical axis; ligament balancing to achieve a rectangular extension
      gap; femoral implant planning to maintain the original joint line and reconstruct
      an equal joint gap in extension and flexion; femora resection perpendicular to
      the mechanical axis; reconstruction of the rectangular flexion gap by rotation of
      the femoral resection; two stage cementing technique for fixation of the original
      implants; check of the final mechanical axis and symmetry of the joint gap over
      the whole range of motion; wound closure. POSTOPERATIVE MANAGEMENT:
      Physiotherapy; continuous passive motion treatment; mobilization with 20 kg
      weight bearing with 2 crutches for 2 weeks, thereafter with 2 crutches and
      incremental full weight bearing for 4 weeks. RESULTS: The analysis of 582
      consecutive navigated total knee arthroplasties showed one case of extension gap
      instability  > 3 mm (0.2%) and 8 patients with flexion gap instability  > 3 mm
      (1.4%). A too tight flexion gap was registered in 23 patients (4.4%), a too wide
      flexion gap in 13 cases (2.5%). The joint line was reconstructed with an average
      inaccuracy of 0 mm, in 17 patients the joint line was elevated  > 3 mm (2.9%).

PMID- 22373790
TI  - [Tibial tubercle osteotomy].
AB  - OBJECTIVE: Tibial tubercle osteotomy facilitates access to the knee joint without
      excessive tension of the extensor apparatus with the lateral parapatellar
      approach and the medial parapatellar approach in case of contracture or revision
      arthroplasty. INDICATIONS: Inadequate exposure of the knee joint with the lateral
      parapatellar approach and inadequate exposure of the knee joint with the medial
      parapatellar approach in case of contracture and revision arthroplasty.
      CONTRAINDICATIONS: Severe periarticular osteoporosis or bone atrophy after knee
      arthroplasty and damage to the patella tendon insertion due to previous
      operations. SURGICAL TECHNIQUE: A bone block 8-10 cm long is excised with the
      tibial tubercle using an oscillating saw. A step cut inferior to the tibial
      plateau is created with a chisel. Refixation is performed with two cortical
      screws. Alternatively, in case of poor bone quality, refixation is accomplished
      with two cerclage wires. POSTOPERATIVE MANAGEMENT: In case of stable refixation,
      full weight bearing is allowed with an extension brace for 2-4 weeks and passive
      flexion is increased as tolerated. In case of poor bone quality, it is
      recommended that full weight bearing be postponed for 6 weeks, whereby full
      flexion is regained in 30 degrees  steps at 2, 4, and 6 weeks postoperatively.
      RESULTS: From 2001-2004, 67 osteotomies of the tibial tubercle were performed for
      revision arthroplasty. During follow-up in 2010, no pseudarthrosis or dislocation
      was noticed. Postoperatively, two hematoma and one skin necrosis had to be
      revised. The risk of hematoma and pseudarthrosis or dislocation of the fragment
      can be minimized by using the correct operative technique.

PMID- 22373791
TI  - Handgrip strength by dynamometry does not identify malnutrition in individual
      preoperative outpatients.
AB  - BACKGROUND & AIMS: Low handgrip strength by dynamometry is associated with
      increased postoperative morbidity, higher mortality and reduced quality of life.
      The aim of this study was to evaluate the accuracy of four algorithms in
      diagnosing malnutrition by measuring handgrip strength. METHODS: We included 504
      consecutive preoperative outpatients. Reference standard for malnutrition was
      defined based on percentage involuntary weight loss and BMI. Diagnostic
      characteristics of the handgrip strength algorithms (Alvares-da-Silva, Klidjian,
      Matos, Webb) were expressed by sensitivity, specificity, positive and negative
      predictive value, false positive and negative rate. RESULTS: The prevalence of
      malnutrition was 5.8%. Although Klidjian showed the highest sensitivity (79%, 95%
      CI 62%-90%), 6 out of 29 malnourished patients were falsely identified as well
      nourished (false positive rate 21%, 95% CI 9%-38%). In contrast, this algorithm
      showed the lowest positive predictive value (8%, 95% CI 5%-13%). Matos presented
      the highest positive predictive value; the post-test probability increased to 13%
      (95% CI 8%-20%). The 1-minus negative predictive value ranged between 3% and 5%
      for all algorithms. CONCLUSIONS: None of the algorithms derived from handgrip
      strength measurements was found to have a diagnostic accuracy good enough to
      introduce handgrip strength as a systematic institutional screening tool to
      detect malnutrition in individual adult preoperative elective outpatients.

PMID- 22373794
TI  - Latent microvolt T-wave alternans in survivors of unexplained cardiac arrest
      unmasked by epinephrine challenge.
AB  - BACKGROUND: The arrhythmogenic substrate in survivors of unexplained cardiac
      arrest (UCA) has not been defined. OBJECTIVES: To test the hypothesis that
      patients with UCA have latent repolarization abnormalities, in particular T-wave
      alternans (TWA), which may be unmasked with epinephrine (EPI) challenge. METHODS:
      We prospectively studied 10 UCA survivors (46 +/- 9 years) and 11 first-degree
      relatives (FDRs) of sudden death victims (37 +/- 14 years). Patients with UCA
      underwent standard clinical testing, which was normal. FDRs had normal clinical
      history and testing. All subjects underwent an EPI infusion (0.05, 0.1, and 0.2
      MUg/(kg.min), 5 minutes each dose) while recording continuous digital 12-lead
      electrocardiograms. Corrected QT interval and QT variability index were evaluated
      at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose by using the
      spectral method. Positive (+) TWA at each dose was defined as V(alt) > 0 with k
      >= 3 in 1 or more 128-beat segment in >=2 electrocardiogram leads. A novel
      metric, TWA burden, reflecting V(alt) integrated over time (s), was also
      evaluated for each EPI dose. RESULTS: There was no difference between UCA
      survivors and FDRs with respect to heart rate, QT, corrected QT interval, or QT
      variability index at baseline or during EPI. At baseline, +TWA was similar
      between UCA survivors and FDRs (10% vs 0%; P = NS). During EPI, +TWA was more
      prevalent in UCA survivors than in FDRs (80% vs 18%; P = .009). TWA burden was
      greater in UCA survivors than in FDRs during EPI 0.1 (P = .039) and EPI 0.2
      MUg/(kg.min) (P = .009). CONCLUSIONS: UCA survivors are more likely to
      demonstrate latent TWA compared with FDRs, which becomes manifest with EPI. This
      novel finding provides evidence for an arrhythmogenic substrate in UCA survivors.

PMID- 22373795
TI  - Identifying the high-risk Brugada syndrome patient: let us get personal.

PMID- 22373796
TI  - Alteration of hepatic structure and oxidative stress induced by intravenous
      nanoceria.
AB  - Beyond the traditional use of ceria as an abrasive, the scope of nanoceria
      applications now extends into fuel cell manufacturing, diesel fuel additives, and
      for therapeutic intervention as a putative antioxidant. However, the biological
      effects of nanoceria exposure have yet to be fully defined, which gave us the
      impetus to examine its systemic biodistribution and biological responses. An
      extensively characterized nanoceria (5 nm) dispersion was vascularly infused into
      rats, which were terminated 1 h, 20 h or 30 days later. Light and electron
      microscopic tissue characterization was conducted and hepatic oxidative stress
      parameters determined. We observed acute ceria nanoparticle sequestration by
      Kupffer cells with subsequent bioretention in parenchymal cells as well. The
      internalized ceria nanoparticles appeared as spherical agglomerates of varying
      dimension without specific organelle penetration. In hepatocytes, the
      agglomerated nanoceria frequently localized to the plasma membrane facing bile
      canaliculi. Hepatic stellate cells also sequestered nanoceria. Within the
      sinusoids, sustained nanoceria bioretention was associated with granuloma
      formations comprised of Kupffer cells and intermingling CD3+ T cells. A
      statistically significant elevation of serum aspartate aminotransferase (AST)
      level was seen at 1 and 20 h, but subsided by 30 days after ceria administration.
      Further, elevated apoptosis was observed on day 30. These findings, together with
      increased hepatic protein carbonyl levels on day 30, indicate ceria-induced
      hepatic injury and oxidative stress, respectively. Such observations suggest a
      single vascular infusion of nanoceria can lead to persistent hepatic retention of
      particles with possible implications for occupational and therapeutic exposures.

PMID- 22373797
TI  - Validation of an in vitro contractility assay using canine ventricular myocytes.
AB  - Measurement of cardiac contractility is a logical part of pre-clinical safety
      assessment in a drug discovery project, particularly if a risk has been
      identified or is suspected based on the primary- or non-target pharmacology.
      However, there are limited validated assays available that can be used to screen
      several compounds in order to identify and eliminate inotropic liability from a
      chemical series. We have therefore sought to develop an in vitro model with
      sufficient throughput for this purpose. Dog ventricular myocytes were isolated
      using a collagenase perfusion technique and placed in a perfused recording
      chamber on the stage of a microscope at ~36  degrees C. Myocytes were stimulated
      to contract at a pacing frequency of 1 Hz and a digital, cell geometry
      measurement system (IonOptixTM) was used to measure sarcomere shortening in
      single myocytes. After perfusion with vehicle (0.1% DMSO), concentration-effect
      curves were constructed for each compound in 4-30 myocytes taken from 1 or 2 dog
      hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21
      inactive compounds, as defined by their effect in dog, cynolomolgous monkey or
      humans. By comparing the outcome of the assay to the known in vivo contractility
      effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was
      78%. With a throughput of 6-8 compounds/week from 1 cell isolation, this assay
      may be of value to drug discovery projects to screen for direct contractility
      effects and, if a hazard is identified, help identify inactive compounds.

PMID- 22373800
TI  - Clinical and pathological parameters predicting extracapsular disease in patients
      undergoing a radical prostatectomy for clinically localized prostate cancer.
AB  - To determine the epidemiological, clinical and pathological factors that can
      potentially predict extracapsular extension of prostate cancer in patients
      undergoing radical prostatectomy for clinically localized disease. We
      retrospectively analyzed the medical records of patients who undergone radical
      prostatectomy from January 2001 until November 2010. Patients age, prostate
      volume, PSA, PSA density, percent of cancer in prostate biopsy material, presence
      of cancer in biopsy cores of the right lobe or the left lobe or both lobes,
      Gleason summary, 1st Gleason pattern and 2nd Gleason pattern were analyzed for
      their predictive ability. From 187 studied patients, 44 of them (23.5%) had
      extracapsular disease. Multivariate analyses revealed that smaller prostate
      volumes and the presence of malignancy in both lobes after prostate biopsy were
      significant predictors for non-organ confined disease in the total population and
      in patients with Gleason score >= 7. Presence of malignancy in both lobes was the
      only significant predictive factor in patients with PSA <= 10 and in those with
      Gleason score <= 6. Prostate volume and positive cores for malignancy from both
      lobes after prostate biopsy are preoperative data that can be used for prediction
      of extracapsular disease. This information can be valuable in cases a nerve
      sparing radical prostatectomy is planned.

PMID- 22373798
TI  - Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in
      human lung epithelial cells.
AB  - Carbon nanotube (CNT) has a promising usage in the field of material science for
      industrial purposes because of its unique physicochemical property. However,
      intraperitoneal administration of CNT was reported to cause mesothelioma in
      experimental animals. Chronic inflammation may contribute to carcinogenesis
      induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed
      during inflammation and may play a role in CNT-induced carcinogenesis. In this
      study, we examined 8-nitroguanine formation in A549 human lung alveolar
      epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent
      immunocytochemistry. Both MWCNTs with diameter of 20-30 nm (CNT20) and 40-70 nm
      (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 MUg/ml
      (p<0.05), which persisted for 24h, although there was no significant difference
      in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the
      expression of inducible nitric oxide synthase (iNOS) for 24 h (p<0.05). MWCNTs
      also significantly increased the level of nitrite, a hydrolysis product of
      oxidized NO, in the culture supernatant at 4 and 8 h (p<0.05). MWCNT-induced 8
      nitroguanine formation and iNOS expression were largely suppressed by inhibitors
      of iNOS (1400 W), nuclear factor-kappaB (Bay11-7082), actin polymerization
      (cytochalasin D), caveolae-mediated endocytosis (methyl-beta-cyclodextrin, MBCD)
      and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron
      microscopy revealed that MWCNT was mainly located in vesicular structures in the
      cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These
      results suggest that MWCNT is internalized into cells via clathrin- and caveolae
      mediated endocytosis, leading to inflammatory reactions including iNOS expression
      and resulting nitrative DNA damage, which may contribute to carcinogenesis.

PMID- 22373802
TI  - Ultrasound evaluation of patients with moderate and severe carpal tunnel
      syndrome.
AB  - The objective of this study is to determine cut-off points for the crosssectional
      areas of the median nerve proximal and distal to carpal tunnel in moderate and
      severe Carpal Tunnel Syndrome (CTS) and compare the results of our study with
      those available in the literature. Forty-three patients with upper limb pain
      other than CTS and 36 patients with idiopathic CTS enrolled into the study. The
      diagnosis and categorization of CTS were based on electrophysiologic criteria of
      the American Academy of Neurology. Median nerve cross-sectional areas were
      measured. Arithmetic mean values and standard deviation of each variable were
      measured. Student t-test and chi-squared test were applied to compare continuous
      and dichotomous variables between CTS and non-CTS control groups. Ultimately the
      diagnostic performances of the test characteristics including sensitivity,
      specificity, positive and negative predictive values were measured. Mean cross
      sectional area of the nerve is higher in moderate than severe CTS proximal and
      distal to carpal tunnel. We accepted cut-off points of 11.5 mm2 and 13.5 mm2 for
      cross-sectional areas of the proximal and distal portions of carpal canal
      respectively. The sensitivity, specificity, positive and negative predictive
      values for the proximal inlet are 83%, 90.7%, 65.5% and 55.7%; and for the distal
      outlet are 36.1%, 93%, 81.2% and 63.4% respectively. We suggest that ultrasound
      is a good diagnostic modality for patients referred to tertiary care centers
      which categorized as moderate CTS.

PMID- 22373801
TI  - Lack of association between interleukin-18 -607 C/A gene polymorphism and
      pulmonary tuberculosis in Zahedan, Southeast Iran.
AB  - Interleukin-18 (IL-18) plays a critical role in immune response, contributing to
      the pathogenesis and pathophysiology of infectious diseases. Polymorphisms in the
      IL-18 genes are known to influence expression levels and may be associated with
      outcome of infections. The objective of this study was to determine whether the
      presence of IL-18 polymorphisms -607 A/C (rs1946518) was associated with
      tuberculosis disease. We investigated the functional polymorphism of IL-18
      (rs1946518) in 174 patients with pulmonary tuberculosis (PTB) and 177 healthy
      subjects. Genotype analysis was done using tetra amplification refractory
      mutation system-PCR (T-ARMS-PCR). The allelic and genotypic frequencies of the IL
      18 polymorphism did not differ significantly between PTB and the controls. Our
      finding suggests that IL-18 polymorphism (rs1946518) may not be a risk factor for
      susceptibility to tuberculosis in a sample of Iranian population. Further studies
      are required to validate our findings.

PMID- 22373803
TI  - Antidiabetic and neuroprotective effects of Trigonella foenum-graecum seed powder
      in diabetic rat brain.
AB  - Trigonella foenum-graecum seed powder (TSP) has been reported to have
      hypoglycemic and hyperinsulinemic action. The objective of the study was to
      examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced
      alterations in blood glucose, insulin levels and activities of membrane linked
      enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase,
      glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane
      fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female
      Wistar rats weighing between 180 and 220 g were made diabetic by a single
      injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were
      given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A
      significant increase in lipid peroxidation was observed in diabetic brain. The
      increased lipid peroxidation following chronic hyperglycemia was accompanied with
      a significant increase in the neurolipofuscin deposition and Ca2+ levels with
      decreased activities of membrane linked ATPases and antioxidant enzymes in
      diabetic brain. A decrease in synaptosomal membrane fluidity may influence the
      activity of membrane linked enzymes in diabetes. The present study showed that
      TSP treatment can reverse the hyperglycemia induced changes to normal levels in
      diabetic rat brain. TSP administration amended effect of hyperglycemia on
      alterations in lipid peroxidation, restoring membrane fluidity, activities of
      membrane bound and antioxidant enzymes, thereby ameliorating the diabetic
      complications.

PMID- 22373805
TI  - Arteriovenous fistula after femoral artery puncture leading to pulmonary edema:
      the role of ultrasonography.
AB  - Local complications of arterial puncture include hematoma, pseudoaneurysm and
      formation of arteriovenous fistula (AVF). The latter could cause ischemia of the
      particular extremity or can be hemodynamically significant especially in patients
      suffering from congestive heart failure. We report a case of femoro-femoral AVF
      after thin needle arterial puncture for blood drawing. The development of this
      iatrogenic AVF led to pulmonary edema. The patient stabilized completely after
      surgical closure of the AVF. The AVF was diagnosed by duplex Doppler
      ultrasonography and this method was also used for estimation of blood flow
      through the AVF. We discuss the role of ultrasound AVF diagnostics and the method
      of flow calculation.

PMID- 22373804
TI  - Case report: pelvic actinomycosis.
AB  - A case of pelvic actinomycosis is presented. The patient is 42-year-old female
      with a 5 weeks history of pelvic pain. An intrauterine device (IUD) was taken out
      3 weeks ago. There is a lump length 9 cm between rectus muscles. Ultrasound,
      magnetic resonance imaging (MRI) and histology are used to make the diagnosis.
      Actinomycosis can mimic the tumour disease. The definitive diagnosis requires
      positive anaerobic culture or histological identification of actinomyces
      granulas. A long lasting antibiotic therapy is performed.

PMID- 22373806
TI  - Blockade of the ganglion impar (walther), using ultrasound and a loss of
      resistance technique.
AB  - The ganglion impar is an unpaired sympathetic structure located at the level of
      the sacrococcygeal joint. Blockade of this structure has been utilised to treat
      chronic perineal pain. Methods to achieve this block often involve the use of
      fluoroscopy which is associated with radiation exposure of staff involved in
      providing these procedures. We report a combined loss of resistance injection
      technique in association with ultrasound guidance to achieve the block.
      Ultrasound was used to identify the sacrococcygeal joint and a needle was shown
      to enter this region. Loss of resistance was then used to demonstrate that the
      needle tip lies in a presacral space. The implication being that any injectate
      would be located in an adequate position. The potential exception would be a
      neurodestructive procedure as radiographic control of needle tip in relation to
      the rectum should be performed and recorded. However when aiming for a diagnostic
      or local anaesthetic based treatment option we feel that this may become an
      accepted method.

PMID- 22373807
TI  - Heart failure treated with low-dose milrinone in a full-term newborn.
AB  - A term newborn with a hypocontractile myocardium complicating persistent
      pulmonary hypertension of the newborn was successfully treated with a low-dose
      phosphodiesterase III inhibitor milrinone. Echocardiography diagnosed heart
      failure with a left ventricular ejection fraction of 35% and a left ventricular
      shortening fraction of 18% and severe persistent pulmonary hypertension of the
      newborn with oxygenation index of 28. Milrinone was started at an initial dose of
      50 mcg/kg, followed by continuous infusion of 0.20 mcg/kg/min. With lowdose
      milrinone oxygenation index decreased to 3 within 6 hours, left ventricular
      ejection fraction and left ventricular shortening fraction increased to 57%, and
      30%, respectively. Low doses of milrinone might be promising in the treatment of
      heart failure and persistent pulmonary hypertension of the newborn in term
      newborns.

PMID- 22373808
TI  - Report from the congress: future of psychiatry and psychiatric training - 19th
      European Federation of Psychiatric Trainees forum in Prague.

PMID- 22373809
TI  - Should minimal residual disease monitoring in acute lymphoblastic leukemia be
      standard of care?
AB  - In acute lymphoblastic leukemia (ALL), the advent of methods to measure disease
      not detectable by morphology, ie, minimal residual disease (MRD), has set a new
      standard to define remission. The clinical importance of MRD has been
      demonstrated by numerous studies using either flow cytometry or polymerase chain
      reaction and involving thousands of patients. Results are in remarkable agreement
      on the association between MRD persistence and risk of subsequent relapse,
      regardless of the MRD detection method used. More recent data indicate that MRD
      can also be informative in specific subgroups of ALL patients, such as infants or
      those with T-lineage ALL. Hence, MRD is now being used in clinical trials to
      inform treatment decisions and guide patients' clinical management. This article
      reviews MRD methodologies and clinical applications with emphasis on recently
      reported technical advances and prognostic associations, and the practical issues
      related to the implementation of MRD monitoring in the clinic.

PMID- 22373810
TI  - Hidden maternal autoimmune thrombocytopenia complicated by fetal subdural
      hematoma-case report and review of the literature.

PMID- 22373811
TI  - The efficacy of silver-embedded polypropylene-grafted polyethylene glycol-coated
      ventricular catheters on prevention of shunt catheter infection in rats.
AB  - PURPOSE: Catheter-related infection is a major complication of
      ventriculoperitoneal shunt in children. The aim of this study is to determine
      inflammatory response and the efficacy of polypropylene-grafted polyethylene
      glycol (PP-g-PEG) copolymer and silver nanoparticle-embedded PP-g-PEG (Ag-PP-g
      PEG) polymer-coated ventricular catheters on the prevention of catheter-related
      infections on a new experimental model of ventriculoperitoneal shunt in rats.
      METHODS: Thirty six Wistar albino rats were divided into six groups: group 1,
      unprocessed sterile silicone catheter-embedded group; group 2, sterile PP-g-PEG
      coated catheter group; group 3, sterile Ag-PP-g-PEG-coated catheter group; group
      4, infected unprocessed catheter group; group 5, infected PP-g-PEG-coated
      catheter group; and group 6, infected Ag-PP-g-PEG-coated catheter group,
      respectively. In all groups, 1-cm piece of designated catheters were placed into
      the cisterna magna. In groups 4, 5, and 6, all rats were infected with 0.2 mL of
      10 * 10(6) colony forming units (CFU)/mL Staphylococcus epidermidis colonies
      before the catheters were placed. Thirty days after implantation, bacterial
      colonization in cerebrospinal fluid and on catheter pieces with inflammatory
      reaction in the brain parenchyma was analyzed quantitatively. RESULTS: Sterile
      and infected Ag-PP-g-PEG-covered groups revealed significantly lower bacteria
      colony count on the catheter surface (ANOVA, 0 +/- 0, p < 0.001; 1.08 +/- 0.18, p
      < 0.05, respectively). There was moderate inflammatory response in the parenchyma
      in group 4, but in groups 5 and 6, it was similar to that of the sterile group
      (ANOVA, 16.33 +/- 3.02, p < 0.001; 4.00 +/- 0.68, p < 0.001, respectively).
      CONCLUSIONS: The PP-g-PEG, especially Ag-PP-g-PEG polymer-coated ventricular
      catheters are more effective in preventing the catheter-related infection and
      created the least inflammatory reaction in the periventricular parenchyma.

PMID- 22373812
TI  - The key surface components of Pasteurella multocida: capsule and
      lipopolysaccharide.
AB  - The capsule and lipopolysaccharide (LPS) of Pasteurella multocida constitute the
      major components of the bacterial cell surface. As well as forming the basis for
      the most widely used classification systems, they play key roles in a range of
      interactions between the bacteria and the hosts they colonize or infect. Both
      polysaccharides are involved in the avoidance of host innate immune mechanisms,
      such as resistance to phagocytosis, complement-mediated killing, and the
      bactericidal activity of antimicrobial peptides; they are therefore essential for
      virulence. In addition, LPS is a major antigen in the stimulation of adaptive
      immune responses to infection.

PMID- 22373813
TI  - Body esteem in Chinese adolescents: effect of gender, age, and weight.
AB  - This study examined the associations of body esteem with gender, age, and Body
      Mass Index (BMI) among 905 Hong Kong adolescents using the Body-Esteem Scale
      (BES). Older age, male gender and lower BMI were associated with better body
      esteem. Multiple regression analyses indicated significant main effects of
      gender, age and weight on BES-Total. Significant interaction effects of gender *
      BMI and gender * age * BMI were also found on BES-Weight (beta = -0.149, p =
      .028) and BES-Total (beta = -0.139, p = .044). Improvement of body esteem with
      age may be associated with age-related BMI differences.

PMID- 22373814
TI  - Plexin-B3 interacts with EB-family proteins through a conserved motif.
AB  - BACKGROUND: Plexins are transmembrane receptors that are highly expressed in the
      central nervous system. They participate in the patterning of neural connections
      and regulation of cell adhesion and motility in many cell types. The aim of this
      study was to characterize novel protein-protein interactions of plexin-B3
      intracellular portion. METHODS: To identify new interactors of plexin-B3 yeast
      two-hybrid screen was performed. We used GST pull-down and co-immunoprecipitation
      to verify those results. Deletion mutants were used to map the interacting
      regions. The physiological relevance of this interaction was assessed with
      neurite outgrowth assay in Neuro2A cell line. RESULTS: We show that the N
      terminal segment of intracellular domain of plexin-B3 interacts with microtubule
      plus end-binding proteins EB1, EB2 and EB3. The corresponding region in human
      plexin-A2, B1 and B3 contains the conserved EB-binding motif SxIP and these
      plexins also associate with EBs indicating the specificity of plexin-EB binding.
      As to the EB proteins, their N-terminal microtubule-binding domain is dispensable
      for plexin interaction. Plexin-EB interaction is involved in neurite growth as
      the synthetic peptide corresponding to the EB-binding region of plexin-B1
      increases significantly the number of neurite tips in Neuro2A cells. CONCLUSIONS:
      Microtubule end-binding proteins EB1, EB2 and EB3 interact with plexin-A2, B1 and
      B3 through a conserved EB-binding motif, which is located in their intracellular
      domain N-terminal segment. GENERAL SIGNIFICANCE: The observed interaction between
      plexin intracellular domain and EBs suggests a novel function for plexins in
      regulating EB-mediated changes in microtubule dynamics and neurite growth.

PMID- 22373815
TI  - Co-ordination behaviour of a novel bisthiourea tripodal ligand: structural,
      spectroscopic and electrochemical properties of a series of transition metal
      complexes.
AB  - The synthesis of a thiourea substituted derivative of tris(pyridyl-2-methyl)amine
      (TPA) is reported. Two of the three pyridine rings are substituted in the 6
      position with benzoylthiourea groups. These thiourea groups undergo
      intramolecular hydrogen bonding to form six-membered rings which leaves one N-H
      group available to form hydrogen bonds with other molecules. This reports details
      how the complexation of this new ligand with transition metal ions yields
      complexes with differing geometries. Seven co-ordinate Mn(II) and Cd(II), six co
      ordinate Ni(II) and five co-ordinate Co(II), Cu(II) and Zn(II) complexes have
      been isolated.

PMID- 22373816
TI  - Complement profile and activation mechanisms by different LDL apheresis systems.
AB  - Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by means of
      selective LDL apheresis is indicated in otherwise uncontrolled familial
      hypercholesterolemia. During blood-biomaterial interaction other constituents
      than the LDL particles are affected, including the complement system. We set up
      an ex vivo model in which human whole blood was passed through an LDL apheresis
      system with one of three different apheresis columns: whole blood adsorption,
      plasma adsorption and plasma filtration. The concentrations of complement
      activation products revealed distinctly different patterns of activation and
      adsorption by the different systems. Evaluated as the final common terminal
      complement complex (TCC) the whole blood system was inert, in contrast to the
      plasma systems, which generated substantial and equal amounts of TCC. Initial
      classical pathway activation was revealed equally for both plasma systems as
      increases in the C1rs-C1inh complex and C4d. Alternative pathway activation (Bb)
      was most pronounced for the plasma adsorption system. Although the anaphylatoxins
      (C3a and C5a) were equally generated by the two plasma separation systems, they
      were efficiently adsorbed to the plasma adsorption column before the "outlet",
      whereas they were left free in the plasma in the filtration system. Consequently,
      during blood-biomaterial interaction in LDL apheresis the complement system is
      modulated in different manners depending on the device composition.

PMID- 22373817
TI  - Fetal membrane patch and biomimetic adhesive coacervates as a sealant for
      fetoscopic defects.
AB  - Iatrogenic preterm premature rupture of membranes after fetoscopic procedures
      affects 10-47% of patients, secondary to the non-healing nature of membranes and
      the separation of layers during the entry. In this study we developed an in vitro
      model to mimic the uterine wall-fetal membrane interface using a water column
      with one end sealed with human fetal membranes and poultry breast, and a defect
      was created with an 11 French trocar. Further, a fetal membrane patch in
      conjunction with multiphase adhesive coacervates modeled after the sandcastle
      worm bioadhesive was tested for sealing of an iatrogenic defect. The sealant
      withstood an additional traction of 12 g for 30-60 min and turbulence of the
      water column without leakage of fluid or slippage. The adhesive is non-toxic when
      in direct contact with human fetal membranes in an organ culture setting. A fetal
      membrane patch with multiphase adhesive complex coacervates may help to seal the
      defect and prevent iatrogenic preterm premature rupture of the membranes.

PMID- 22373818
TI  - A poly(L-lysine)-based hydrophilic star block co-polymer as a protein nanocarrier
      with facile encapsulation and pH-responsive release.
AB  - A hydrophilic star block co-polymer was synthesized, characterized, and evaluated
      as a protein nanocarrier. The star block co-polymer was composed of a
      hyperbranched polyethylenimine (PEI) core, a poly(L-lysine) (PLL) inner shell,
      and a poly(ethylene glycol) (PEG) outer shell. The model protein insulin can be
      rapidly and efficiently encapsulated by the synthesized polymer in aqueous
      phosphate buffer at physiological pH. Complexation between PEI-PLL-b-PEG and
      insulin was investigated using native polyacrylamide gel electrophoresis. The
      uptake of enhanced green fluorescent protein into Ad293 cells mediated by PEI-PLL
      b-PEG was also investigated. The encapsulated insulin demonstrated sustained
      release at physiological pH and showed accelerated release when the pH was
      decreased. The insulin released from the star block co-polymer retained its
      chemical integrity and immunogenicity.

PMID- 22373819
TI  - Cross-talk between phosphorylation and lysine acetylation in a genome-reduced
      bacterium.
AB  - Protein post-translational modifications (PTMs) represent important regulatory
      states that when combined have been hypothesized to act as molecular codes and to
      generate a functional diversity beyond genome and transcriptome. We
      systematically investigate the interplay of protein phosphorylation with other
      post-transcriptional regulatory mechanisms in the genome-reduced bacterium
      Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two
      protein kinases and its unique protein phosphatase identified not only the
      protein-specific effect on the phosphorylation network, but also a modulation of
      proteome abundance and lysine acetylation patterns, mostly in the absence of
      transcriptional changes. Reciprocally, deletion of the two putative N
      acetyltransferases affects protein phosphorylation, confirming cross-talk between
      the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome
      revealed that both PTMs are very common, that (as in Eukaryotes) they often co
      occur within the same protein and that they are frequently observed at
      interaction interfaces and in multifunctional proteins. The results imply
      previously unreported hidden layers of post-transcriptional regulation
      intertwining phosphorylation with lysine acetylation and other mechanisms that
      define the functional state of a cell.

PMID- 22373820
TI  - Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations
      in protein levels.
AB  - The cell cycle is a temporal program that regulates DNA synthesis and cell
      division. When we compared the codon usage of cell cycle-regulated genes with
      that of other genes, we discovered that there is a significant preference for non
      optimal codons. Moreover, genes encoding proteins that cycle at the protein level
      exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes
      expressed in different phases display different codon preferences. Here, we show
      empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase
      of the cell cycle, consistent with the non-optimal codon usage of genes expressed
      at this time, and lowest toward the end of G1, reflecting the optimal codon usage
      of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and
      glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase.
      In light of our findings, we propose that non-optimal (wobbly) matching codons
      influence protein synthesis during the cell cycle. We describe a new mathematical
      model that shows how codon usage can give rise to cell-cycle regulation. In
      summary, our data indicate that cells exploit wobbling to generate cell cycle
      dependent dynamics of proteins.

PMID- 22373821
TI  - Place matters: neighborhood deprivation and cardiometabolic risk factors in the
      Diabetes Study of Northern California (DISTANCE).
AB  - While neighborhood deprivation is associated with prevalence of chronic diseases,
      it is not well understood whether neighborhood deprivation is also associated
      with cardiometabolic risk factors among adults with chronic disease. Subjects (n
      = 19,804) from the Diabetes Study of Northern California (DISTANCE) cohort study,
      an ethnically-stratified, random sample of members of Kaiser Permanente Northern
      California (KPNC), an integrated managed care consortium, with type 2 diabetes
      who completed a survey between 2005 and 2007 and who lived in a 19 county study
      area were included in the analyses. We estimated the association between a
      validated neighborhood deprivation index (NDI) and four cardiometabolic risk
      factors: body mass index (BMI = kg/m2), glycosylated hemoglobin (A1c), low
      density lipoproteins (LDL) and systolic blood pressure (SBP) using multi-level
      models. Outcomes were modeled in their continuous form and as binary indicators
      of poor control (severe obesity: BMI >=35, poor glycemic control: A1c >=9%,
      hypercholesterolemia: LDL >=130 mg/dL, and hypertension: SBP >=140 mmHg). BMI,
      A1c and SBP increased monotonically across quartiles of NDI (p < 0.001 in each
      case); however, LDL was significantly associated with NDI only when comparing the
      most to the least deprived quartile. NDI remained significantly associated with
      BMI and A1c after adjusting for individual level factors including income and
      education. A linear trend (p < 0.001) was observed in the relative risk ratios
      for dichotomous indicators of severe obesity, poor glycemic control, and 2 or
      more poorly controlled cardiometabolic risk factors across NDI quartile. In
      adjusted models, higher levels of neighborhood deprivation were positively
      associated with indicators of cardiometabolic risk among adults with diabetes,
      suggesting that neighborhood level deprivation may influence individual outcomes.
      However, longitudinal data are needed to test the causal direction of these
      relationships.

PMID- 22373822
TI  - Assessment of the green florescence protein labeling method for tracking
      implanted mesenchymal stem cells.
AB  - Although green fluorescent protein (GFP) labeling is widely accepted as a
      tracking method, much remains uncertain regarding the retention of injected GFP
      labeled cells implanted in ischemic organs. In this study, we evaluate the
      effectiveness of GFP for identifying and tracking implanted bone marrow-
      mesenchymal stem cells (BM-MSCs) and the effect of GFP on the paracrine actions
      of these cells. MSCs isolated from rat femur marrow were transduced with a
      recombinant adenovirus carrying GFP. After transplantation of the GFP-labeled BM
      MSCs into the infarct zone of rat hearts, the survival, distribution, and
      migration of the labeled cells were analyzed at 3, 7, 14, and 28 days. To
      evaluate the effect of GFP on the paracrine actions of BM-MSCs, Western blot
      analysis was performed to detect the expression of vascular endothelial growth
      factor (VEGF), b fibroblast growth factor (b FGF), tissue inhibitor of
      metalloproteinase-1 (TIMP-1) and matrix metalloproteinases-2 (MMP-2). GFP was
      successfully expressed by BM-MSCs in vitro. At 14 days after cell transplantation
      the GFP-positive cells could not be detected via confocal microscopy. By using a
      GFP antibody, distinct GFP-positive cells could be seen and quantitative analysis
      showed that the expression volume of GFP was 6.42 +/- 0.92 mm(3) after 3 days,
      1.24 +/- 0.76 mm(3) after 7 days, 0.33 +/- 0.03 mm(3) after 14 days, and 0.09 +/-
      0.05 mm(3) after 28 days. GFP labeling did not adversely affect the paracrine
      actions of BM-MSCs. GFP labeling could be used to track MSC distribution and
      their fate for at least 28 days after delivery to rat hearts with myocardial
      infarction, and this stem cell tracking strategy did not adversely affect the
      paracrine actions of BM-MSCs.

PMID- 22373824
TI  - Self-enucleation: forget Freud and Oedipus, it's all about untreated psychosis.
AB  - Self-enucleation is a rare but serious ophthalmological and psychiatric
      emergency. It has traditionally been considered to be the result of psycho-sexual
      conflicts, including those arising from Freud's Oedipal complex and Christian
      religious teaching. However, an analysis of published case reports suggests that
      self-enucleation is a result of psychotic illnesses such as schizophrenia. Early
      treatment with antipsychotic medication in the case of unilateral or threatened
      self-enucleation might prevent some cases of blindness.

PMID- 22373823
TI  - Genotoxicity of food preservative sodium sorbate in human lymphocytes in vitro.
AB  - The genotoxic effects of antimicrobial food additive sodium sorbate (SS) was
      assessed by using chromosome aberrations (CAs), sister-chromatid exchanges
      (SCEs), and micronucleus (MN) in cultured human lymphocytes and comet assay in
      isolated human lymphocytes. Lymphocytes were treated with four concentrations
      (100, 200, 400 and 800 MUg/ml) of SS as well as a negative (sterile distilled
      water) and a positive control (Mitomycin-C: MMC for cultured lymphocytes and
      H(2)O(2) for isolated lymphocytes). The result of this study indicated that SS
      increased the frequency of CAs at both 24 and 48 h period compared to control.
      When gaps were included, this increase was significant at 200, 400 and 800 MUg/ml
      concentrations at 24 h and, at all concentrations at 48 h treatment time. When
      gaps were excluded, this increase was significant at only 800 MUg/ml
      concentration at both 24 and 48 h treatments. In addition, SS increased SCEs/cell
      and MN frequency at 400 and 800 MUg/ml concentrations at both 24 and 48 h
      compared to negative control. Furthermore, this additive caused DNA damage at all
      concentrations in isolated human lymphocytes after 1 h in vitro exposure. The
      present results show that SS is genotoxic to the human peripheral blood
      lymphocytes in vitro at the highest concentrations.

PMID- 22373825
TI  - Differences in tissue degeneration between preoperative chemotherapy and
      preoperative chemoradiotherapy for colorectal cancer.
AB  - PURPOSE: Preoperative chemoradiotherapy (CRT) for rectal cancer is administered
      to improve local control, but can also induce severe anal dysfunction after
      surgery, while preoperative chemotherapy that significantly reduces the primary
      lesion in rectal cancer has recently been developed. The aim of the study was to
      examine differences in the effects of preoperative CRT and chemotherapy on tissue
      degeneration of patients with colorectal cancer. METHODS: The subjects were 91
      patients, including 68 with rectal cancer who underwent internal sphincteric
      resection with (n = 47, CRT group) or without (n = 21, control group)
      preoperative CRT, and 23 with colorectal cancer who received preoperative FOLFOX
      treatment. Peripheral nerve degeneration was evaluated histopathologically using
      H&E-stained sections, based on karyopyknosis, disparity of the nucleus,
      denucleation, vacuolar or acidophilic degeneration of the cytoplasm, and
      adventitial neuronal changes. RESULTS: The incidence of neural degeneration was
      significantly higher in the CRT group than in the control group and FOLFOX group.
      There were no differences in any items of neural degeneration between the FOLFOX
      and control groups. CONCLUSION: CRT induced marked neural degeneration around the
      rectal tumor. FOLFOX treatment produced mild neural degeneration similar to that
      in the control group.

PMID- 22373826
TI  - Using MDCT to search for recipient vessels for free flaps after multiple
      procedures for head and neck reconstruction.

PMID- 22373827
TI  - Liposuction for chronic lymphoedema of the upper limb: 5 years of experience.
AB  - BACKGROUND: Lymphoedema of the upper limb is a well-recognised complication of
      axillary surgery for breast cancer. Effective long-term treatment of lymphoedema
      by liposuction has previously been demonstrated. In this study we present our
      first five years of experience using this technique in treatment of upper limb
      lymphoedema. METHODS: A prospective analysis of the results of 12 patients who
      underwent liposuction followed by compression therapy for chronic unilateral
      upper limb oedema with up to five years of follow-up was carried out. Hospital
      Anxiety and Depression Score questionnaires and a Visual Analogue Score for
      overall well-being were also completed pre- and post-operatively. RESULTS: The
      mean duration of lymphoedema was seven years (range, 1-14), commencing at a mean
      of one year (range, 0-5) after axillary surgery. The mean excess arm volume at
      admission was 1391 ml and the ratio of the lymphoedematous to the unaffected arm
      was 1.48. The mean total aspirate volume was 1713 ml, of which 87 percent was
      fat. At one year the mean percentage volume reduction compared with the normal
      arm was 101 percent, meaning that the volume of both of patients' arms was
      virtually equivalent, and this reduction was stable with up to 5 years of follow
      up. Postoperatively there were reductions in anxiety (p < 0.05) and depression
      scores, and an improvement in overall well-being. DISCUSSION: Our first five
      years of experience of liposuction combined with application of compression
      garments has demonstrated significant, reproducible, and stable reduction of
      upper limb oedema with improvement of overall well-being and reduction in
      measurable anxiety and depression.

PMID- 22373828
TI  - Transzygomatic Kirschner wire fixation for the treatment of blowout fracture.
AB  - BACKGROUND: Total orbital floor reconstruction with sheet-shape materials is
      available for the treatment of extensive and crushed-type blowout fractures.
      Simple blowout fractures, on the other hand, require only manual reduction
      without fixation. Although several types of blowout fractures do not require
      total reconstruction, some fixation is usually necessary. METHODS: Eighteen cases
      of blowout fracture were treated with transzygomatic Kirschner wire fixation
      between 2002 and 2009. This technique was applied to simple fracture cases in
      which periorbital soft tissue re-herniated through the floor defect into the
      maxillary sinus after manual reduction, despite improvement of the extra-ocular
      muscle entrapment. The wire was used to directly support the fracture segment in
      five cases and used together with a maxillary sinus anterior wall bone graft in
      13 cases. RESULTS: Mean follow-up was 12.5 months. Mild diplopia remained as a
      subjective symptom in one case. None of the cases developed major complications
      or conspicuous scars on the cheek. CONCLUSIONS: Transzygomatic Kirschner wire
      fixation for blowout fracture has the advantages of precise and rigid fixation of
      all parts of the inferior floor, minimal morbidity without requiring an orbital
      approach and long-term safety without artificial remnants. This technique can be
      applied for the treatment of simple blowout fractures.

PMID- 22373829
TI  - Oral tetracyclines may not be effective in treating acne: dominance of the
      placebo effect.
AB  - Oral tetracyclines (tetracycline, doxycycline, minocycline and lymecycline) have
      been commonly regarded as effective for treating both inflammatory and non
      inflammatory acne. An excellent review of efficacy of 57 clinical trials by
      Simonart et al. in 2007 concluded that compared to the baseline before treatment,
      efficacies of all tetracyclines were similar (mean reduction in inflammatory
      lesions and non-inflammatory lesion being 54.3 +/- 1.4% and 45 +/- 2.6%,
      respectively) and were not affected by dosage amount (40 - 1,000 mg per day) and
      treatment period (4 - 24 weeks). These interesting findings may be
      pharmacodynamically rationalized by weak intrinsic anti-acne activity of
      tetracyclines and strong placebo effects. This hypothesis was supported by
      published data indicating that during weeks or months of daily administration,
      the placebo effect approached the effect of minocycline or doxycline in reducing
      acne lesions in three separate studies. The present work suggests the importance
      of considering placebo effects in the evaluation of anti-acne products. The
      treatability of acne was discussed in view of the slow and weak intrinsic anti
      acne property of oral tetracyclines, and the reported fast (within days)
      elimination (curing) of severe acne by intralesional corticosteroids and
      antibiotics. The subantimicrobial or non-antimicrobial doses (e.g., only a small
      fraction) of various oral tetracyclines may be much lower than those commonly
      recognized.

PMID- 22373831
TI  - Potentially inappropriate prescribing for elderly outpatients in Germany: a
      retrospective claims data analysis.
AB  - OBJECTIVE: To quantify the frequency of potentially inappropriate medication
      (PIM) prescribing for outpatients aged 65 years and older using claims data of a
      German statutory health insurance. METHODS: Based on the 2002 Beers criteria for
      PIM use, a retrospective evaluation of drug prescription data in outpatient care
      was conducted for the years 2003 and 2004 using data from a German statutory
      health insurance (AOK) in the area of Saxony. The study was limited to those
      drugs classified as being potentially inappropriate according to the criteria
      independent of existing medical conditions and without any restrictions
      concerning dosage or duration of use, because this information was not available
      from the data. RESULTS: In 2003, 3.3% (408,375) of all 12,513,584 drug
      prescriptions for patients 65 years and older which were analyzed included a PIM
      from the Beers list. In 2004, it was 2.9% (297,524) of 10,126,809 (p < 0.001).
      The most frequently prescribed PIMs were short-acting nifedipine (13.4%),
      indomethacin (12.3%) and diazepam (11.8%) in 2003, and diazepam (14.6%) followed
      by indomethacin (13.7%) and doxazosin (10.9%) in 2004. 21.7% (119,482) and 18.2%
      (98,465) of patients 65 years or older received at least one prescription of a
      PIM in 2003 and 2004, respectively (p < 0.001). In a multivariate logistic
      regression model female gender and a higher number of prescribed drugs were
      significantly associated with an increased frequency of receiving a PIM in both
      years. CONCLUSIONS: In our study, approximately every 5th older patient was
      prescribed at least one PIM. For the future an ongoing update of the Beers
      criteria to further include newer agents and an adaptation to the different
      situation in European countries is desirable.

PMID- 22373832
TI  - Antihypertensive treatment and risk of dementia: a retrospective database study.
AB  - OBJECTIVE: Vascular risk factors play an important role in the pathogenesis of
      vascular dementia, as well as in Alzheimer disease. The effect of
      antihypertensive medication on risk of dementia is unclear. The aim was to
      investigate the association between antihypertensive prescriptions and incident
      dementia, using a primary care database. METHODS: The analysis was based on 575
      general and internal practices in Germany (10/2003 - 09/2008) (Disease analyzer
      database). Antihypertensive medication (ATC codes) during 3 years before newly
      diagnosed dementia (ICD codes or specific medication) in 1,297 patients was
      compared to 1,297 controls without dementia after matching for age (mean age:
      80.6 +/- 8.6 y), sex (females: 62%) and date of diagnosis. Conditional logistic
      regression was used to calculate crude and adjusted odds ratios (95% confidence
      intervals). RESULTS: Betablocker prescriptions (>= 1 per year over 3 y) showed a
      significant inverse association with newly diagnosed dementia (Odds ratio, OR:
      0.79 95% CI 0.61 - 0.99) after adjusting for demographic covariates, health care
      use, and cardiovascular and neurological comorbidity. In the fully adjusted
      model, ACE inhibitors also tended to be inversely associated with incident
      dementia, but failed statistical significance (OR 0.84 95% CI 0.65 - 1.08).
      Calcium channel blockers were positively related to cognitive impairment only in
      the crude analysis. The other drug groups were not significantly related to
      dementia (diuretics OR: 0.89; 0.67 - 1.19; angiotensin- 1-inhibitors OR: 1.04;
      0.66 - 1.64). CONCLUSIONS: This practice-based case-control study indicated a
      possible protective effect of some antihypertensive agents (betablockers, ACE
      inhibitors) on the development of dementia. Randomized controlled trials are
      required to confirm this finding.

PMID- 22373830
TI  - Electroencephalogram-based pharmacodynamic measures: a review.
AB  - Pharmacokinetics and pharmacodynamics can provide a useful modeling framework for
      predicting drug activity and can serve as a basis for dose optimization.
      Determining a suitable biomarker or surrogate measure of drug effect for
      pharmacodynamic models can be challenging. The electroencephalograph is a widely
      available and non-invasive tool for recording brainwave activity simultaneously
      from multiple brain regions. Certain drug classes (such as drugs that act on the
      central nervous system) also generate a reproducible electroencephalogram (EEG)
      effect. Characterization of such a drug-induced EEG effect can produce
      pharmacokinetic/pharmacodynamic models useful for titrating drug levels and
      expediting development of chemically-similar drug analogs. This paper reviews the
      relevant concepts involved in pharmacokinetic/pharmacodynamic modeling using EEG
      based pharmacodynamic measures. In addition, examples of such models for various
      drugs are organized by drug activity as well as chemical structure and presented.

PMID- 22373833
TI  - Once daily nifedipine: the formulation dictates the pharmacokinetic
      characteristics and the therapeutic responses.
AB  - Nifedipine as a pharmacologic agent for treating hypertension and angina pectoris
      has been available worldwide since the early 1980's. However, the formulation of
      nifedipine has undergone a number of modifications over time to improve the
      pharmacokinetic profile and administration regimen from 3 times daily to once
      daily. Nifedipine Gastrointestinal Therapeutic System (GITS) is the most widely
      studied of the once daily formulations from both a pharmacokinetic and clinical
      perspective. Nifedipine GITS was registered in most major countries worldwide
      based on both clinical pharmacology and clinical trial data in adequately powered
      studies. Moreover, outcome trials in both hypertension (INSIGHT) and angina
      pectoris (ACTION) have been completed and published. Other once daily modified
      release nifedipine formulations are available in a number of countries but
      limited published data is available on these formulations. A Pubmed (Medline)
      search using the terms "nifedipine pharmacokinetics" yielded 162 articles of
      which 7 provided detailed pharmacokinetic values in head to head comparisons of
      nifedipine GITS and another once a day formulation. These published
      pharmacokinetic studies have failed to show that any of the other formulations is
      consistently bioequivalent to the reference formulation, nifedipine GITS. In
      addition, other Pubmed searches yielded limited data from comparative clinical
      studies, which show significant differences in favor of the nifedipine GITS
      formulation in terms of blood pressure control and activation of the sympathetic
      nervous system. With limited data comparing once daily formulations of nifedipine
      to nifedipine GITS and no data comparing between other once a day formulations,
      for both pharmacokinetic and therapeutic reasons, the evidence indicates that
      patients should not be switched between once daily formulations of nifedipine.

PMID- 22373834
TI  - Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the effects of tocilizumab on methotrexate and 7
      hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to
      explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a
      marker of inflammation. METHODS: Methotrexate (10 - 25 mg) was administered
      orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg
      tocilizumab intravenously. Blood samples for pharmacokinetic analyses were
      collected on Days 1, 15, and 43 and for pharmacodynamics (CRP) throughout the
      study. RESULTS: 90% CIs for mean effect ratios (Day 15/Day 1 and Day 43/Day 1) of
      methotrexate and 7-hydroxymethotrexate (AUClast and Cmax) were close to or within
      the bioequivalence boundaries (80 - 125%). CRP normalized within 1 week after
      tocilizumab injection and remained within normal limits for 3 weeks. CONCLUSION:
      Tocilizumab and methotrexate can be administered concurrently without dosage
      adjustments.

PMID- 22373835
TI  - A positron emission tomography microdosing study with sertraline in healthy
      volunteers.
AB  - OBJECTIVE: This study explored microdosing methods for evaluating the
      distribution and pharmacokinetics (PK) of a central nervous system (CNS) drug
      candidate. METHODS: We used sertraline as a model drug. In this open-label, one
      arm, three-period, multiple-dosing study, 10 healthy male volunteers received 6
      day administrations of sertraline at doses of 5, 25 or 50 mg/d in three different
      periods. Before the first dose of Period 1, and 24 h after the last dose of each
      period, an intravenous bolus of [11C]sertraline was injected for positron
      emission tomography (PET) scanning. After the sixth dose in each period, serial
      blood samples were collected at scheduled intervals over 48 h; then serum
      sertraline concentrations were determined with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). RESULTS: Sertraline was distributed in the brain within
      20 min, and it was highly distributed in the putamen, cingulate, and thalamus.
      Linearity in steady-state Cmax and AUClast were observed in the 5 - 50 mg dose
      range. The results suggested that microdosing with PET was a useful method for
      exploring the bloodbrain- barrier penetration and distribution of a candidate CNS
      drug. CONCLUSIONS: This study described a microdosing method that combined PET
      with LC-MS/MS for determining the brain distribution and PK characteristics of a
      CNS drug candidate.

PMID- 22373836
TI  - In vitro activity of green tea extract against Leishmania major promastigotes.
AB  - BACKGROUND: Systemic and topical treatment options against Leishmaniasis are
      limited to a few drugs with inconsistent efficacy and unacceptable side effects
      and none of them is suitable for all forms of the disease. OBJECTIVE: The aim of
      this study was to search the in vitro activity of green tea extract against L.
      major promastigotes and compare it with glucantime. METHODS: Extract was prepared
      by percolation method. The extract was dried and dissolved in DMSO 1% solvent.
      Leishmania major promastigotes treated with 6 concentrations (3, 6, 12, 24, 48,
      96 mg/ml) of the extract. As control positive group glucantime 85 mg/ml and
      additional untreated control group were included in this study. All cultures were
      performed in triplicate. The promastigotes were also counted and their
      flagellate's motilities were assessed microscopically. RESULTS: Ethanolic extract
      of green tea showed significant leishmanicidal activity against L. major
      promastigotes in different concentrations. Notably there was a concordance in
      anti-leishmanial effect of the ethanol extract with the increasing of the dosage
      (3, 6, 12, 24, 48, 96 mg/ml). In comparison with glucantime the mean alive
      promastigotes in 12 mg/ml concentration of green tea was almost as same as 85
      mg/ml glucantime and higher green tea extract concentrations were higher
      effective than glucantime. CONCLUSION: Our study revealed a novel pharmacological
      activity against promastigotes of L. major and suggests that green tea extract
      has the potential of being used in leishmaniasis but more studies are needed to
      find out its activity against amastigote and appropriate route of application.

PMID- 22373837
TI  - Novel nonsense mutation of ABHD5 in Dorfman-Chanarin syndrome with unusual
      findings: a challenge for genotype-phenotype correlation.
AB  - Dorfman-Chanarin syndrome is a rare neutral lipid disorder characterised by
      icthyosis, hepatic steatosis and multisystemic involvement of varying magnitude.
      It is an autosomal recessive disease caused by mutations in the ABHD5 gene. We
      report a consanguineous family of Afgani origin, with four affected siblings who
      were found to have a novel homozygous nonsense mutation g. [27606 G > T]; [27606
      G > T]. The clinical findings were unusual in the form of early cirrhosis and
      hepatic decompensation in one sibling, presence of corneal opacities in male
      siblings and tessellated fundus in all affected children. Steatosis was minimal
      in liver biopsy specimens and all children had low vitamin D levels. Genotype
      phenotype correlations have not been possible in Dorfman-Chanarin syndrome and
      the present report raises further challenges for the same.

PMID- 22373838
TI  - Therapeutic options for advanced prostate cancer: 2011 update.
AB  - Up to 40% of male patients diagnosed with prostate cancer develop metastatic
      disease that generally responds to initial chemical or surgical castration, but
      this eventually progresses despite castrate levels of testosterone, termed
      castration-resistant prostate cancer (CRPC). A large phase 3 trial of abiraterone
      acetate in patients who have progressed following docetaxel based chemotherapy
      were published in 2011 and dramatically proved that CRPC is still androgen
      dependant and responds to CYP17 inhibition. Overall survival benefits were also
      reported for a novel tubulin-binding drug, cabazitaxel, tested as second-line
      chemotherapy after docetaxel failure; for sipuleucel-T, an autologous dendritic
      cell therapy, in chemotherapy-naive patients; for MDV3100, a novel antiandrogen,
      and for radium-223, which is a bone-seeking alpha-irradiation-emitting
      radioisotope. Denosumab, a monoclonal antibody against receptor activator of
      nuclear factor-kB ligand, was shown to be superior to zoledronic acid for
      prevention of skeletal-related events in prostate cancer patients with metastatic
      bone disease. This review will focus on the recent developments in the field of
      CRPC.

PMID- 22373840
TI  - Nickel poly-acetylide carbonyl clusters: structural features, bonding and
      electrochemical behaviour.
AB  - The reactions of [NEt(4)](2)[Ni(6)(CO)(12)] with miscellaneous carbon halides
      (e.g. CCl(4), C(4)Cl(6)) in CH(2)Cl(2) have been extensively investigated
      particularly focusing on the stoichiometric ratio of the reagents and reaction
      temperature. This allowed the preparation of the previously known acetylide
      clusters [Ni(16)(C(2))(2)(CO)(23)](4-), [HNi(25)(C(2))(4)(CO)(32)](3-) and
      [Ni(22)(C(2))(4)(CO)(28)Cl](3-), as well as isolation and full characterisation
      of the closely related [Ni(17)(C(2))(2)(CO)(24)](4-) and
      [Ni(25)(C(2))(4)(CO)(32)](4-) tetraanions. From a structural point of view, all
      these clusters are based on a Ni(16) square orthobicupola which contain
      interstitial C(2), Ni(eta(2)-C(2))(4) or Ni(2)(MU-eta(2)-C(2))(4) moieties,
      displaying rather short C-C bonds. Electrochemical studies reveal that all these
      species undergo different redox processes, even if their stability is rather
      limited. This is corroborated by an extensive analysis of the interaction between
      interstitial C(2) acetylide units and the metal cluster cage by Extended Huckel
      Molecular Orbital (EHMO) calculations, which indicates that tightly bonded C-C
      units are less effective than isolated C-atoms in stabilising the cluster cage.

PMID- 22373841
TI  - [Allergies].

PMID- 22373839
TI  - Journal of Artificial Organs 2011: the year in review.

PMID- 22373842
TI  - [Prevalence and socio-economic relevance of allergies in Germany].
AB  - Within the last five decades, the worldwide prevalence of allergic diseases such
      as asthma, hay fever, or food allergies has increased dramatically. Germany
      follows a similar trend; several studies have shown increased numbers of allergic
      diseases in this period. Although allergic diseases do not exhibit high mortality
      rates, the loss of quality of life as shown by studies conducted by the World
      Health Organization (WHO) is considerable. Additional health-economical analyses
      documented that allergic patients more frequently occupy services of the health
      care system in Germany. The treatment of allergies and the increasing
      consultation rates cause rising costs and an increasing burden for the national
      economy. Currently it is possible to control allergic diseases such as asthma by
      a precise diagnosis or identification of the causative allergen. However, a
      considerable reduction in the prevalence of allergic disease and its therapy
      costs can only be expected if causative therapies and effective prevention
      strategies are available.

PMID- 22373843
TI  - [Determinants of asthma among children and adolescents in Germany. Results of the
      German Health and Examination Survey for Children and Adolescents (KiGGS)].
AB  - In this study, associations between current asthma and possible determinants were
      studied using data of the German Health Interview and Examination Survey for
      Children and Adolescents ("Studie zur Gesundheit von Kindern und Jugendlichen in
      Deutschland," KiGGS). In this nationwide cross-sectional survey, 17,461 subjects
      aged 0-17 years were examined between 2003 and 2006. Data collection included a
      medical examination of the child, an interview of the parents, and written
      questionnaires. Apart from prevalence estimates, multivariate logistic regression
      analyses were performed. Increasing age and male sex, previous atopic diseases of
      the child, a positive family history of allergic diseases and low birth weight
      were significant risk factors of asthma, as were overweight and moldy walls in
      the residence. Breast feeding was not associated with a reduced risk of asthma.
      Low age at delivery of the mother and living in rural or provincial regions were
      shown to be protected. Overall, this study suggests that allergies of the parents
      and previous atopic disease of the child are the strongest determinants of
      asthma. However, environmental factors (mold on walls, living in rural and
      provincial towns) and lifestyle factors could also modify asthma risk.

PMID- 22373844
TI  - [Classification of specific IgE antibodies in children with hay fever and other
      atopic diseases in Germany. Results of the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS)].
AB  - The dependencies between sensitization to common allergens (mono- and
      polysensitization, IgE level and patterns) and symptomatic hay fever and other
      atopic diseases, respectively, in children and adolescents are shown in this
      analysis. The evaluation was based on the KiGGS ("Kinder- und
      Jugendgesundheitssurvey") study. Our analysis was performed using complex samples
      methods with SPSS. Participants were interviewed by a physician using a validated
      questionnaire asking for atopic diseases and symptoms. Specific IgE levels were
      measured from the age of 3 years on by using the ImmunoCap(r) test system. The
      prevalences of hay fever and polysensitizations both significantly increase with
      increasing age of the participants, while boys are more often affected than girls
      and migrants less often regarding sensitizations. Prevalence of hay fever
      decreases with increasing number of older siblings and increases with atopy of
      one or both parents. Different positive correlations between increasing IgE
      levels and hay fever were identified, the greatest association was observed with
      herbal inhalative allergens and cross-reacting food allergens. Lowest IgE levels
      to nearly all of the tested allergens show a positive correlation with hay fever
      prevalence. In conclusion, the study indicates that the clinical definition of
      the lowest positive IgE levels as "marginal" should be discussed as well as
      indications for specific immunotherapy.

PMID- 22373845
TI  - [Clinical epidemiology and prevention of contact allergies. The Information
      Network of Departments of Dermatology (IVDK) as a register and surveillance
      system].
AB  - A total of 56 departments of dermatology from Germany, Austria, and Switzerland
      collaborate to study the clinical epidemiology of contact allergies (CA). Data
      generated in the course of the diagnostic work-up of CA (e.g., patch test data)
      have been stored since 1989 in the data center in Gottingen, Germany, including
      data for more than 200,000 patients (March 2011). These data can be used as a
      register and as a surveillance system. Analysis of the register may identify and
      quantify risk factors of sensitization to an allergen, which is exemplified with
      the case of the allergen para-phenylenediamine. It turned out that-in addition to
      the risk factor hair dyeing-other important risk factors must be considered. In
      contrast, data collected every 6 months (from approximately 6,000 patients) allow
      for time-trend analyses of allergens, thus, identifying allergens of concern,
      which is of utmost importance for early preventive intervention. Here, the
      epidemiology of allergies to epoxy resins serves as an example. Continuous
      monitoring of contact allergens will also be mandatory in the future, as the CA
      premarketing screening systems will have imperfect predictive values with regard
      to human CA risk. Unfortunately, the (current) national regulatory framework
      severely hampers clinical surveillance/epidemiology of contact sensitization and,
      thus, prevention of contact allergy.

PMID- 22373846
TI  - [The revised guideline on Primary Allergy Prevention].
AB  - The recommendations of the revised guideline Primary Allergy Prevention published
      in 2009 are summarized and discussed. The updated guidelines do not further
      recommend reducing house dust mite allergen exposure as a measure of primary
      prevention. New suggestions include the avoidance of overweight, and reduction of
      the exposure to indoor and/or outdoor air pollutants. In line with the current
      guidelines, there is no scientific evidence that prolonged introduction of solid
      food is an allergy-preventive measure. Consequently, even children with a family
      history of atopy can introduce solid foods at the beginning of the 5th month. The
      recommendations on avoiding environmental tobacco smoke, breast feeding over 4
      months, avoiding a mold-promoting indoor climate, vaccination according to
      current recommendations, and avoidance of furry pets (especially cats) in risk
      babies have remained unchanged.

PMID- 22373847
TI  - [Role of allergen-specific immunotherapy (desensitization) for the treatment of
      allergies in Germany. Current situation].
AB  - Allergen-specific immunotherapy (SIT, desensitization) is applied monthly with
      subcutaneous injections (SCIT) or sublingually (SLIT) with droplets or tablets on
      a daily basis. Numerous immunological changes during SIT induce long-lasting
      tolerance. Efficacy has been demonstrated by a number of controlled studies for
      insect venom hypersensitivity (SCIT), allergic rhinoconjunctivitis (SCIT, SLIT
      particularly in grass pollen allergy), and allergic asthma (SCIT > SLIT). SIT is
      indicated in children and adults with severe allergic reactions from insect
      venoms (e.g., bee, wasp) or cumbersome symptoms from pollen, house dust mites or
      mold allergens and proven immediated-type allergy. Contraindications must be
      considered individually. SIT is performed for 3 years, in case of venom allergy 3
      5 years. Severe systemic reactions are rare after SCIT. After SLIT rather local
      allergic symptoms of short duration occur in the mouth and throat. At present,
      the number prescriptions for SIT has decreased due to inadequate reimbursement of
      allergy-related services (diagnostics, therapies, monitoring). In the future,
      inferior medical care of allergic patients in Germany is expected, who until now
      have benefited from the preventive effects of SIT (reduced risk of developing
      asthma and new allergic sensitizations).

PMID- 22373848
TI  - [The therapy allergens ordinance ("Therapieallergene-Verordnung"). Background and
      effects].
AB  - Medicinal products for specific immunotherapy as causal treatment of allergies
      exist in Germany as authorized medicinal products manufactured batchwise in
      advance and as named patient products (NPPs) which are exempted from the
      authorization procedure. With the therapy allergens ordinance ("Therapieallergene
      Verordnung (TAV)") which has been in effect since 14 November 2008, this
      exemption was restricted to therapy allergens indicated for the treatment of rare
      allergies. NPPs containing at least one of the therapy allergens listed in the
      annex of the TAV had to be notified to the Paul-Ehrlich-Institut (PEI) by 14 May
      2009 to retain their marketability. It had to be stated whether applications for
      marketing authorization will be submitted for the respective NPPs or if they will
      be sold off by 14 November 2011. The bulks which are used for manufacturing of
      the NPPs have been subject to official batch release by PEI since October 2009.
      Nearly 7,000 NPPs of 10 pharmaceutical entrepreneurs were notified. Marketing
      authorization applications were submitted for 123 NPPs. This illustrates that,
      although there are authorized therapy allergens available for all allergens
      listed in the annex of the TAV, a large number of NPPs with unknown quality,
      safety, and efficacy have been marketed.

PMID- 22373849
TI  - [Governmental batch sample testing of allergen products].
AB  - Allergen products for specific immunotherapy of type I allergies were first
      authorized for the German market in the 1970s. In addition to finished products
      manufactured in advance and in batches, so-called named patient products have
      recently been defined as Medicinal Products by the German Medicinal Products Act
      ("Arzneimittelgesetz", AMG 14th Revision 2005). Some allergen products previously
      marketed as named patient products are now required to obtain marketing
      authorization according to the German ordinance for therapy allergens. Products
      have to be batch released by the competent German Federal Agency, the Paul
      Ehrlich-Institut (PEI). Samples of product batches are delivered to the PEI in
      order to perform experimental quality controls. With regard to named patient
      products, PEI tests batch samples of the bulk extract preparations used for
      manufacturing of the respective, named patient products. The institute releases
      approximately 2,800 allergen product batches annually.

PMID- 22373850
TI  - [Workplace-related respiratory allergies. Current developments].
AB  - It is common that the inhalation of occupational allergens induces occupational
      airway diseases, but the inducers are diverse and complex, and the pathomechanism
      of the disease is not clear in every case. Only few allergens have been studied
      in detail (e.g., wheat flour and natural rubber latex), and most of the
      occupational airway sensitizers have only been documented as case reports. This
      review describes occupational type I aeroallergens according to their source
      (plant, animal, microbial, and chemical) and workplace application area. New
      aspects on the diagnosis and legal preventive regulations for occupational
      allergic airway diseases are described.

PMID- 22373851
TI  - [Assessment of the sensitizing potency of cosmetic ingredients and commodities.
      How will the ingredients of cosmetics and commodities be tested in Europe today
      and tomorrow?].
AB  - Cosmetics and certain commodities are applied or used by consumers directly on
      the skin. Creams may remain on the skin for longer periods, hair is dyed multiple
      times per year, nickel ions can be released from studs and piercings in areas of
      skin damage or migrate from toy materials into the skin of children. Accordingly,
      using or handling such products always entails a risk for developing a contact
      allergy. Moreover, daily usage and repeated contacts to certain cosmetics and
      commodities might lead to repeated elicitation of contact eczema in people
      already sensitized against allergenic ingredients. Unfortunately, contact allergy
      is not curable. For the assessment of the allergenic potential of chemicals, only
      testing based on animal experiments was available in the past. In 2003, the 7(th)
      amendment of the Cosmetics Directive 76/768/EWG laid down a ban on animal testing
      of cosmetic ingredients and from 2013 a general marketing ban of such products as
      well. Therefore, the development and validation of non-animal methods for
      assessing the toxicological endpoint sensitization/allergenic potency of
      chemicals is a major task for the years ahead and remains equally a challenge for
      industry and regulatory agencies.

PMID- 22373852
TI  - [The registry for severe allergic reactions in German-speaking countries. Recent
      data and perspectives].
AB  - The anaphylaxis registry collects data from patients with severe allergic
      reactions via an online questionnaire. Currently 85 centers from Germany,
      Austria, and Switzerland are involved. The data are entered by allergists. They
      cover demographical data, data of the elicitors, concomitant diseases,
      circumstances of the allergic reactions, and information about the treatment of
      affected patients. Until to date the data show that the elicitor profile of
      severe allergic reactions depends on the age of patients. In childhood, food
      allergens are the most frequent elicitors, whereas in adults insect stings are
      most frequently the cause of anaphylaxis. The analysis of concomitant diseases
      suggests that allergic diseases like allergic asthma, allergic rhinitis or atopic
      dermatitis occur frequently in children with anaphylaxis, whereas in adults
      cardiovascular diseases predominate. The data about the medical treatment of
      affected patients show that antihistamines and corticosteroids are often used in
      German-speaking countries for the treatment of severe allergic reactions, whereas
      adrenaline, the drug of choice, is only rarely used (< 20%). The registry is an
      important clinical epidemiological tool which allows to generate research but
      also disease management-related questions.

PMID- 22373853
TI  - [Hidden allergens in processed food. The consumer perspective].
AB  - Despite improved allergen-labeling and careful avoidance strategies, hidden
      allergens in food are a substantial risk for unintended reactions in food allergy
      sufferers. Unpublished data from a survey of the German Allergy and Asthma
      Association (Deutscher Allergie- und Asthmabund, DAAB) show that 85% of 738
      questioned food allergic patients have experienced at least one allergic reaction
      from each prepacked products as well as food sold loose. Almost half of the
      participants said to have not received information of a food allergen as an
      ingredient or possible trace on the label. Different possibilities are discussed
      under which food allergens can be hidden in processed products, like
      incomprehensible labeling, labeling gaps, unexpected occurrence of allergens as
      well as cross contaminations or allergens in loose products. To each of the seven
      highlighted sources of hidden allergens in food, practical examples are given as
      well as proposals for the improvement of the situation from consumer view. The
      aim is to indicate possibilities and measures for politics and industry by which
      allergic consumers and their social circle are able to make an informed choice
      concerning the safe consumption of a certain product and to protect themselves
      from unintentional reactions.

PMID- 22373854
TI  - [Current aspects in risk assessment of allergen traces in foodstuffs].
AB  - In contrast to usual ingredients in processed packaged foodstuffs, there are no
      suitable and binding regulations for the labeling of unintentional allergen
      traces in these foods as yet. This situation is unsatisfactory in regard to the
      fact that even traces of undeclared "hidden" allergens can constitute a
      considerable health risk for food allergic consumers. Furthermore, the
      unintentional cross-contact (cross-contamination) of allergens is also an issue
      in regard to food manufacturer product liability and due diligence. Therefore,
      stakeholders consider imperative need for the scientific determination of maximum
      tolerable levels of allergen traces in order to establish thresholds for legally
      binding food labeling. In addition to conventional toxicological risk
      assessments, the risk assessment of allergen traces that would be necessary in
      this context nowadays also incorporates modern approaches such as benchmark
      procedures and probabilistic modeling and methods. The scientific debate
      concerning the establishment of safe threshold levels continues, and a consensus
      must still be reached.

PMID- 22373855
TI  - [Assessment of allergenicity of genetically modified food crops].
AB  - The placing on the European Union's market of genetically modified crops requires
      authorization by the European Commission which is based on the proof that the
      derived foods are as safe as their conventional counterparts. The assessment of
      potential allergenicity is part of the necessary investigations recommended in
      the updated Guidance Document of the Scientific Panel on Genetically Modified
      Organisms (GMO) of the European Food Safety Authority (EFSA), which is based on
      internationally agreed recommendations. All genetically modified crops which so
      far have been authorized in the European Union were evaluated by the EFSA GMO
      Panel which considered it unlikely that their overall allergenicity has been
      altered.

PMID- 22373857
TI  - [Effects of menthol as an additive in tobacco products and the need for
      regulation].
AB  - Menthol is the most widely used and the most prominent tobacco additive in
      tobacco products advertised and marketed by the tobacco industry. Besides its
      characteristic flavor, it possesses a variety of pharmacological properties
      facilitating tobacco smoke inhalation and potentiating dependence. These
      properties of menthol not only favor tobacco initiation and consumption but can
      also prevent smoking cessation. This article summarizes the effect of menthol as
      an additive in tobacco products and its effect on tobacco consumption that causes
      a number of chronic diseases and premature death and, therefore, counteracts
      tobacco control measures. Currently, there is no legislative regulation in
      Germany that considers the health hazard, addiction-enhancing and attractiveness
      increasing properties of additives permitted in tobacco products. Effective
      regulation or even a ban could contribute to a reduction of tobacco consumption
      and, hence, save many people from a long-lasting tobacco dependence.

PMID- 22373858
TI  - [Health and illness in the country, state NRW, and its communities. Results from
      the 2009 German Microcensus].
AB  - The health-for-all policy framework needs data for action. Results from the
      German Microcensus can be extrapolated to the population at the country, state
      ("Bundeslander"), and community levels. Most of the information in the 2009
      Microcensus was given under the statutory obligation; providing health
      information in the supplementary program was optional. The selection rate was 1%
      of the population. The Microcensus' continuous sampling method during the year,
      thus, determines illness rates as an average for the year. There are distinct
      health disparities between not only the states but also between communities in
      North Rhine-Westphalia. Annual average illness rates for 2009 are associated in
      NRW with influencing social factors, e.g., education. Illness rates rise with
      decreasing net income for the past month. Blue-collar workers suffered more often
      from illness or accident injuries at the time. The levels of illness in the
      overall employable population increase in the communities of NRW with the
      proportion of inhabitants who receive governmental financial aid or unemployment
      benefits to secure their basic livelihood. The Microcensus has the potential to
      be a source for systematic and harmonized monitoring concerning health in the
      country, states, and communities of Germany.

PMID- 22373859
TI  - [Preimplantation genetic diagnosis. Unanswered questions in light of the new
      law].

PMID- 22373860
TI  - [Possibilites and limitations of retrospective research on cause of death within
      the framework of a nationwide epidemiological study].
AB  - Cause-specific mortality is an important endpoint in longitudinal epidemiological
      studies to research causal health links and carry out individual process
      analyses. As in Germany no national mortality register exists, state-specific
      data-protection conditions for and approaches to cause of death studies were
      researched and tested within the framework of a pilot project. The database was
      provided by a sample of deceased study participants from the 1998 nationwide
      health survey. Under the given conditions, cause of death research in a
      nationwide epidemiological study is possible in principle, but requires a great
      deal of time and effort. In Rhineland-Palatinate research needs to be carried out
      in a timely manner as the health authorities' retention period for death
      certificates is limited to minimum of 5 years. In Berlin the research situation
      is particularly difficult as, while the death certificates are held 3 years by
      the statistics bureau, this department cannot release any pseudonymous data. In
      Berlin it is possible to research the cause of death for some of the deceased
      through the doctors and hospitals that issued the death certificates and through
      the GKR Berlin-Brandenburg (in keeping with the special data protection measures
      of the cancer registry). In North Rhine Westphalia the written consent obtained
      during people's lifetimes, including an explicit release from medical
      confidentiality, is required to carry out cause of death research. In all other
      German states exceptions are possible, in all cases requiring the consent of the
      state's data protection commissioners. The results of the pilot project underline
      the need for a national mortality register. Until this is established the
      approach used in the pilot study can be used and, working together with the state
      and national data protection authorities and with the highest national health
      authorities, can be further optimized in order to avoid losing data and to use
      resources efficiently.

PMID- 22373861
TI  - [Detection of Legionella in drinking water. Sampling, method and evaluation].

PMID- 22373862
TI  - High-fat diet alters gene expression in the liver and colon: links to increased
      development of aberrant crypt foci.
AB  - BACKGROUND: Obesity is associated with an increased risk of colon cancer. High
      fat diets that lead to obesity may be a contributing factor, but the mechanisms
      are unknown. AIMS: This study examines susceptibility to azoxymethane (AOM)
      induced precancerous lesions in mice in response to consumption of either a low
      or a high-fat diet and associated molecular changes in the liver and colon.
      METHODS: Gene markers of xenobiotic metabolism, leptin-regulated inflammatory
      cytokines and proliferation were assessed in liver and colon in response to high
      fat feeding to determine links with increased sensitivity to AOM. RESULTS: High
      fat feeding increased development of AOM-induced precancerous lesions and was
      associated with increased CYP2E1 gene expression in the liver, but not the colon.
      Leptin receptors and the colon stem cell marker (Lgr5) were down-regulated in the
      proximal colon, with a corresponding up-regulation of the inflammatory cytokine
      (IL6) in response to high-fat feeding. Notably in the distal colon, where
      aberrant crypt foci develop in response to AOM, the proliferative stem cell
      marker, Lgr5, was significantly up-regulated with high-fat feeding. CONCLUSIONS:
      The current study provides evidence that high-fat diets can alter regulation of
      molecular markers of xenobiotic metabolism that may expose the colon to
      carcinogens, in parallel with activation of beta-catenin-regulated targets
      regulating colon epithelial cells. High-fat diets associated with obesity may
      alter multiple molecular factors that act synergistically to increase the risk of
      colon cancer associated with obesity.

PMID- 22373863
TI  - The spontaneous course of liver enzymes and its correlation in nonalcoholic fatty
      liver disease.
AB  - BACKGROUND: The course of liver enzymes and their clinical correlations in
      nonalcoholic fatty liver disease (NAFLD) remains largely undescribed. AIMS: The
      objective of this study was to determine the spontaneous course of liver enzymes,
      and the association between changes in liver enzymes with changes in body weight
      and liver histology in NAFLD. METHODS: Follow-up data were prospectively
      collected for 2 years in 73 untreated patients with NAFLD. Liver enzymes were
      measured every 3 months, and liver biopsy repeated at 2 years. RESULTS: A
      significant improvement in serum levels of aminotransferases, alkaline
      phosphatase, and gamma-glutamyltransferase levels, and a significant decrease in
      albumin levels occurred with no significant change in body weight over the 2
      years. During this period, alanine aminotransferase levels were persistently
      elevated in 68% of patients, fluctuated between normal and elevated in 22% of
      patients, and normalized in 10% of patients. There was no clear-cut correlation
      between the pattern of alanine aminotransferase levels and changes in steatosis,
      inflammation, hepatocyte ballooning, or fibrosis stage over time. CONCLUSIONS:
      Liver enzyme levels and aminotransferase activity are insensitive tools to follow
      changes in liver histological features in NAFLD. These data should be taken into
      consideration in patient counseling and monitoring, and in the design of future
      therapeutic trials.

PMID- 22373864
TI  - miR-301a is a candidate oncogene that targets the homeobox gene Gax in human
      hepatocellular carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNA) are a group of noncoding small RNAs that repress
      mRNA expression or induce mRNA degradation by binding to the 3'-untranslated
      regions of mRNAs. MiRNAs have been connected closely with the development of
      cancers such as hepatocellular carcinoma (HCC). However, the overexpression of
      microRNA-301a (miR-301a) has seldom been connected with tumorigenesis in HCC.
      AIMS: This study aims to characterize the function of upregulated miR-301a in HCC
      and show how the downstream growth arrest-specific homeobox (Gax) is negatively
      regulated by miR-301a. METHODS: The expression of miR-301a and Gax was detected
      using real-time PCR on HCC tissues and adjacent non-tumorous tissues. The
      luciferase reporter assay was used to assess Gax as a target of miR-301a. The
      nuclear factor kappaB (NF-kappaB) was measured by western blot after inhibiting
      miR-301a and enhancing Gax. The functions of miR-301a in vivo in HCC cells were
      measured by migration and invasion assays and flow cytometry. RESULTS: MiR-301a
      was significantly upregulated and Gax was downregulated in HCC samples compared
      with in the matching nontumoral tissues. Inhibiting miR-301a expression caused
      the upregulation of Gax and repressed NF-kappaB expression. We have shown that
      miR-301a plays an important role in increasing proliferation, migration and
      invasion and in inhibiting apoptosis of HCC cells. CONCLUSIONS: miR-301a is
      frequently upregulated in HCC and modulates NF-kappaB expression by negatively
      regulating Gax.

PMID- 22373865
TI  - A novel group therapy for children with ADHD and severe mood dysregulation.
AB  - OBJECTIVE: No psychosocial treatments have been developed for children with ADHD
      and severe mood dysregulation (SMD) despite the significant prevalence and
      morbidity of this combination. Therefore, the authors developed a novel treatment
      program for children with ADHD and SMD. METHOD: The novel therapy program
      integrates components of cognitive-behavioral therapies for affect regulation
      with a parent-training intervention for managing recurrent defiant behaviors. It
      consists of nine 105-min child and parent groups run in unison. A pilot trial was
      conducted with seven participants with ADHD and SMD ages 7 to 12 who were on a
      stable stimulant regimen. RESULTS: Six of the seven (86%) families completed the
      program. Participants showed large improvements in depressive symptoms, mood
      lability, and global functioning. Milder improvements in externalizing behaviors
      were observed. CONCLUSION: Results suggest the feasibility and potential efficacy
      of the therapy program for children with ADHD and SMD and warrant a larger
      controlled trial.

PMID- 22373867
TI  - Getting to grips with Supplementary Information.

PMID- 22373866
TI  - Minimally invasive treatment of varicose veins: Endovenous laser ablation (EVLA).
AB  - Varicose veins are a frequently encountered medical condition. In the era of
      minimally invasive surgery, several techniques, in the treatment of varicose
      veins, have been developed in the last few years. One of the most frequently used
      new techniques is endovenous laser ablation. Fibrotic sealing of the treated vein
      lumen is the final result. The vein ablation is obtained under local - tumescent
      anaesthesia and the patients can be treated in an office setting with immediate
      return to full activity. Safety and effectiveness seem to be the major
      characteristics and advantages of this technique.

PMID- 22373869
TI  - Secreted miRNAs suppress atherogenesis.
AB  - Endothelial-vascular smooth muscle cell communication has a critical role in
      cardiovascular homeostasis and the pathogenesis of atherosclerosis. A study now
      demonstrates extracellular-vesicle-mediated transfer of the atheroprotective
      microRNAs miR-143/145 between endothelial and vascular smooth muscle cells,
      providing compelling evidence that intercellular transport of miRNAs can
      influence a pathological process, namely atherosclerosis.

PMID- 22373868
TI  - Multiple modes of cytoplasmic dynein regulation.
AB  - In performing its multiple cellular functions, the cytoplasmic dynein motor is
      subject to complex regulation involving allosteric mechanisms within the dynein
      complex, as well as numerous extramolecular interactions controlling subcellular
      targeting and motor activity. Recent work has distinguished high- and low-load
      regulatory modes for cytoplasmic dynein, which, combined with a diversity of
      targeting mechanisms, accounts for a very broad range of functions.

PMID- 22373875
TI  - Complement anaphylatoxin C3a as a novel independent prognostic marker in heart
      failure.
AB  - OBJECTIVES: The purpose of this study was to evaluate complement activation in a
      heart failure cohort. Based on their powerful biological activity, we
      hypothesized that the levels of anaphylatoxin C3a are related to pathological
      signs and outcomes in heart failure. DESIGN, SETTING AND PATIENTS: Complement
      activation products C3a and SC5b9 were determined in 182 consecutive CHF patients
      (single centre, prospective cohort study), with a left ventricular ejection
      fraction <45%. Mortality and re-hospitalisation due to the progression of CHF
      were assessed after a median follow-up of 14 months. INTERVENTIONS: None.
      RESULTS: In the univariate analysis, high level of anaphylatoxin C3a was
      significantly associated with clinical events (p < 0.0001), whereas SC5b9 showed
      a tendency of association (p = 0.094). In multivariable Cox analysis, adjusted
      for age, NT-proBNP, diastolic blood pressure, body mass index (BMI), haemoglobin
      and creatinine levels, C3a was a significant predictor of HF-related re
      hospitalization or death (HR 1.189 per 1-SD increase, 95% CI 1.023-1.383), and of
      cardiovascular events or death (HR 1.302, CI 1.083-1.566). C3a was strongly
      associated with the presence of peripheral oedema, inflammatory markers (CRP,
      prealbumin, IL-6, sTNFRI, sTNFRII), heat-shock protein 70 levels and endothelial
      activation markers (von-Willebrand factor and endothelin-1). CONCLUSIONS: Results
      of the present study showed that complement activation is strongly linked to
      unfavourable outcomes in heart failure. High levels of anaphylatoxin C3a
      predicted re-hospitalization, cardiovascular events and mortality in adjusted
      survival model. Increased C3a levels were associated with biomarkers of acute
      phase reaction, inflammation, cellular stress response, endothelial-cell
      activation and oedematous complications independently from disease severity.

PMID- 22373876
TI  - Preferential growth of short aligned, metallic-rich single-walled carbon
      nanotubes from perpendicular layered double hydroxide film.
AB  - Direct bulk growth of single-walled carbon nanotubes (SWCNTs) with required
      properties, such as diameter, length, and chirality, is the first step to realize
      their advanced applications in electrical and optical devices, transparent
      conductive films, and high-performance field-effect transistors. Preferential
      growth of short aligned, metallic-rich SWCNTs is a great challenge to the carbon
      nanotube community. We report the bulk preferential growth of short aligned
      SWCNTs from perpendicular Mo-containing FeMgAl layered double hydroxide (LDH)
      film by a facile thermal chemical vapor deposition with CH(4) as carbon source.
      The growth of the short aligned SWCNTs showed a decreased growth velocity with an
      initial value of 1.9 nm s(-1). Such a low growth velocity made it possible to get
      aligned SWCNTs shorter than 1 MUm with a growth duration less than 15 min. Raman
      spectra with different excitation wavelengths indicated that the as-grown short
      aligned SWCNTs showed high selectivity of metallic SWCNTs. Various kinds of
      materials, such as mica, quartz, Cu foil, and carbon fiber, can serve as the
      substrates for the growth of perpendicular FeMoMgAl LDH films and also the growth
      of the short aligned SWCNTs subsequently. These findings highlight the easy route
      for bulk preferential growth of aligned metallic-rich SWCNTs with well defined
      length for further bulk characterization and applications.

PMID- 22373877
TI  - Moxonidine into the lateral parabrachial nucleus reduces renal and hormonal
      responses to cell dehydration.
AB  - The deactivation of the inhibitory mechanisms with injections of moxonidine
      (alpha2-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial
      nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular
      dehydrated rats. In the present study, we investigated the changes in the urinary
      sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats
      treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with
      injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with
      stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral
      injections of moxonidine (0.5 nmol/0.2 MUl) into the LPBN decreased i.g. 2 M NaCl
      induced diuresis (4.6+/-0.7 vs. vehicle: 7.4+/-0.6 ml/120 min) and natriuresis
      (1.65+/-0.29 vs. vehicle: 2.53+/-0.17 mEq/120 min), whereas the previous
      injection of the alpha2-adrenoceptor antagonist RX 821002 (10 nmol/0.2 MUl) into
      the LPBN abolished the effects of moxonidine. Moxonidine injected into the LPBN
      reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6+/
      2.8 and 2.2+/-0.3 vs. vehicle: 25.7+/-7 and 4.3+/-0.7 pg/ml, respectively).
      Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3
      M NaCl intake (7.5+/-1.7 vs. vehicle: 0.5+/-0.2 mEq/2 h) and produced positive
      sodium balance (2.3+/-1.4 vs. vehicle: -1.2+/-0.4 mEq/2 h) in rats that had
      access to water and NaCl. The present results show that LPBN alpha2-adrenoceptor
      activation reduces renal and hormonal responses to intracellular dehydration and
      increases sodium and water intake, which facilitates sodium retention and body
      fluid volume expansion.

PMID- 22373878
TI  - An N-terminal G11A mutation in HOXD13 causes synpolydactyly and interferes with
      Gli3R function during limb pre-patterning.
AB  - Synpolydactyly (SPD) is a distal limb anomaly characterized by incomplete digit
      separation and the presence of supernumerary digits in the syndactylous web. This
      phenotype has been associated with mutations in the homeodomain or polyalanine
      tract of the HOXD13 gene. We identified a novel mutation (G11A) in HOXD13 that is
      located outside the previously known domains and affects the intracellular half
      life of the protein. Misexpression of HOXD13(G11A) in the developing chick limb
      phenocopied the human SPD phenotype. Finally, we demonstrated through in vitro
      studies that this mutation has a destabilizing effect on GLI3R uncovering an
      unappreciated mechanism by which HOXD13 determines the patterning of the limb.

PMID- 22373879
TI  - Words of wisdom. Re: Long-term follow-up of T1 high-grade bladder cancer after
      intravesical Bacille Calmette-Guerin (BCG) treatment.

PMID- 22373880
TI  - Words of wisdom. Re: Markers predicting response to Bacillus Calmette-Guerin
      immunotherapy in high-risk bladder cancer patients: a systematic review.

PMID- 22373881
TI  - Words of wisdom. Re: Fluorescence and white light cystoscopy for detection of
      carcinoma in situ of the urinary bladder.

PMID- 22373882
TI  - Words of wisdom. Re: N,N'-dithiobisphthalimide, a disulfide aromatic compound, is
      a potent spermicide agent in humans.

PMID- 22373883
TI  - Words of wisdom. Re: Posterior lumbar vein off the retrohepatic inferior vena
      cava: a novel anatomical variant with surgical implications.

PMID- 22373884
TI  - Words of wisdom. Re: Abiraterone and increased survival in metastatic prostate
      cancer.

PMID- 22373885
TI  - Evolving medicolegal concepts: editorial comment.

PMID- 22373886
TI  - Effect of a lifestyle intervention on adiposity and fitness in socially
      disadvantaged subgroups of preschoolers: a cluster-randomized trial (Ballabeina).
AB  - OBJECTIVE: A multidimensional lifestyle intervention performed in 652
      preschoolers (72% of migrant, 38% of low educational level (EL) parents) reduced
      body fat, but not BMI and improved fitness. The objective of this study is to
      examine whether the intervention was equally effective in children of migrant
      and/or low EL parents. METHODS: Cluster-randomized controlled single blinded
      trial, conducted in 2008/09 in 40 randomly selected preschools in Switzerland.
      The culturally tailored intervention consisted of a physical activity program and
      lessons on nutrition, media use and sleep. Primary outcomes included BMI and
      aerobic fitness. Secondary outcomes included %body fat, waist circumference and
      motor agility. RESULTS: Children of migrant parents benefitted similarly from the
      intervention compared to their counterparts (p for interaction>= 0.09). However,
      children of low EL parents benefitted less, although these differences did not
      reach statistical significance (p for interaction>= 0.06). Average intervention
      effect sizes for BMI were -0.10, -0.05, -0.11 and 0.04 kg/m(2) and for aerobic
      fitness were 0.55, 0.20, 0.37 and -0.05 stages for children of non-migrant,
      migrant, middle/high EL and low EL parents, respectively. CONCLUSIONS: This
      intervention was similarly effective among preschoolers of migrant parents
      compared to their counterparts, while children of low EL parents benefitted less.

PMID- 22373887
TI  - Functional benefits of citrus fruits in the management of diabetes.

PMID- 22373888
TI  - Synthesis of stable free base secochlorins and their corresponding metal
      complexes from meso-tetraarylporphyrin derivatives.
AB  - Cleavage reactions of 2,3-diamino-meso-tetraarylporphyrins and meso
      tetraarylporphyrins fused to imidazole rings afforded secochlorins including
      stable free base derivatives.

PMID- 22373889
TI  - Hierarchical modeling of ammonia adsorption in functionalized metal-organic
      frameworks.
AB  - The adsorption of ammonia in four metal-organic frameworks modified with
      different functional groups (-OH, -C=O, -Cl, -COOH) was investigated using a
      hierarchical molecular modeling approach. To describe the hydrogen bonding and
      other strong interactions between NH(3) and the surface functional groups, a set
      of Morse potential parameters were obtained by fitting to energies from quantum
      chemical calculations at the MP2 level of theory. We describe a systematic force
      field parameterization process, in which the Morse parameters were fitted using
      simulated annealing to match a large number of single-point MP2 energies at
      various distances and angles. The fitted potentials were then used in grand
      canonical Monte Carlo simulations to predict ammonia adsorption isotherms and
      heats of adsorption in functionalized MIL-47, IRMOF-1, IRMOF-10, and IRMOF-16.
      The results show that ammonia adsorption can be significantly enhanced by using
      materials with appropriate pore size, strongly interacting functional groups, and
      high density of functional groups.

PMID- 22373890
TI  - Cauda equina syndrome in the setting of longstanding instrumented spinal fusion.

PMID- 22373891
TI  - Reoperation of deep brain stimulation in patients with essential tremor.

PMID- 22373892
TI  - Visual impairment after endovascular treatment: does stent placement increase the
      incidence?

PMID- 22373893
TI  - Using field-evolved resistance to Cry1F maize in a lepidopteran pest to
      demonstrate no adverse effects of Cry1F on one of its major predators.
AB  - Spodoptera frugiperda (JE Smith) represents the first documented case of field
      evolved resistance to a genetically engineered crop expressing an insecticidal
      protein from Bacillus thuringiensis (Bt). In this case it was Cry1F-expressing
      maize (Mycogen 2A517). The ladybird beetle, Coleomegilla maculata, is a common
      and abundant predator that suppresses pest populations in maize and many other
      cropping systems. Its larvae and adults are polyphagous, feeding on aphids,
      thrips, lepidopteran eggs and larvae, as well as plant tissues. Thus, C. maculata
      may be exposed to Bt proteins expressed in genetically engineered crops by
      several pathways. Using Cry1F-resistant S. frugiperda larvae as prey, we
      evaluated the potential impact of Cry1F-expressing maize on several fitness
      parameters of C. maculata over two generations. Using Cry1F resistant prey
      removed any potential prey-mediated effects. Duration of larval and pupal stages,
      adult weight and female fecundity of C. maculata were not different when they
      were fed resistant S. frugiperda larvae reared on either Bt or control maize
      leaves during both generations. ELISA and insect-sensitive bioassays showed C.
      maculata were exposed to bioactive Cry1F protein. The insecticidal protein had no
      effect on C. maculata larvae, even though larvae contained 20-32 ng of Cry1F/g by
      fresh weight. Over all, our results demonstrated that the Cry1F protein did not
      affect important fitness parameters of one of S. frugiperda's major predators and
      that Cry1F protein did not accumulate but was strongly diluted when transferred
      during trophic interactions.

PMID- 22373894
TI  - Muscle activation in the loaded free barbell squat:  a brief review.
AB  - The purpose of this article was to review a series of studies (n = 18) where
      muscle activation in the free barbell back squat was measured and discussed. The
      loaded barbell squat is widely used and central to many strength training
      programs. It is a functional and safe exercise that is obviously transferable to
      many movements in sports and life. Hence, a large and growing body of research
      has been published on various aspects of the squat. Training studies have
      measured the impact of barbell squat loading schemes on selected training
      adaptations including maximal strength and power changes in the squat. Squat
      exercise training adaptations and their impact on a variety of performance
      parameters, in particular countermovement jump, acceleration, and running speed,
      have also been reported. Furthermore, studies have reported on the muscle
      activation of the lower limb resulting from variations of squat depth, foot
      placement, training status, and training intensity. There have also been studies
      on the impact of squatting with or without a weight belt on trunk muscle
      activation (TMA). More recently, studies have reported on the effect of
      instability on TMA and squat performance. Research has also shown that muscle
      activation of the prime movers in the squat exercise increases with an increase
      in the external load. Also common variations such as stance width, hip rotation,
      and front squat do not significantly affect muscle activation. However, despite
      many studies, this information has not been consolidated, resulting in a lack of
      consensus about how the information can be applied. Therefore, the purpose of
      this review was to examine studies that reported muscle activation measured by
      electromyography in the free barbell back squat with the goal of clarifying the
      understanding of how the exercise can be applied.

PMID- 22373895
TI  - Efficacy of two different stretch training programs (passive vs. proprioceptive
      neuromuscular facilitation) on shoulder and hip range of motion in older people.
AB  - The aim of this study was to determine the influence of 2 methods of stretch
      training (passive and proprioceptive neuromuscular facilitation [PNF]) on range
      of motion (ROM) in older people between the age of 60 and 70 years over a period
      of 13 weeks. Fifty-four participants (39 women and 15 men) were divided into 3
      groups: passive (n = 17; 66.5 +/- 6.5 years), PNF (n = 17; age, 64.7 +/- 4.0
      years old), and control (n = 17; age, 66.4 +/- 4.5 years). The subjects trained 2
      times per week on nonconsecutive days for 13 weeks. Each training session
      included 2 flexibility exercises focused on the shoulder and hip joints. The PNF
      group performed 6 seconds of passive stretching, 3 seconds of muscular
      contractions, and 2 seconds of relaxation. The passive group performed 10 seconds
      of stretching and 5 seconds of relaxation. This sequence was repeated 3 times by
      each group. The control group did not perform any stretching. In the PNF group,
      there was an increase in hip ROM (p < 0.001) between pretest and posttest in the
      passive group and an improvement (p < 0.001) was observed between pretest and
      posttest, whereas in the control group, there was a significant decrease (p <
      0.01) in hip ROM between pretest and posttest. In shoulder ROM, there was an
      increase (p < 0.001) between pretest and posttest in the passive group and an
      improvement (p < 0.001) was observed between pretest and posttest in the PNF
      group. There were no changes in shoulder ROM between pretest and posttest in the
      control group. The analysis of variance showed significant differences in hip and
      shoulder ROM between passive and control groups and PNF and control groups, but
      no significant differences were found between passive and PNF. The main finding
      was that the ability of physically active older people to increase ROM in
      response to stretching techniques is similar for both passive and PNF techniques.

PMID- 22373896
TI  - The role of viruses in the pathogenesis of peritonsillar abscess.
AB  - Peritonsillar abscess (PTA) is the most frequent complication of acute
      tonsillitis and a prevalent cause for acute admission to otorhinolaryngology
      departments. Our aim was to examine the role of viruses in the pathogenesis of
      PTA, as this has not previously been considered. We examined both palatine
      tonsils from 25 patients undergoing acute tonsillectomy for PTA, using PCR-based
      assays for herpes simplex virus-1 and -2 (HSV-1 and -2), adenovirus, Epstein-Barr
      virus (EBV), influenza A and B, and respiratory syncytial virus (RSV) A and B. We
      similarly examined tonsils from 55 patients undergoing elective tonsillectomy due
      to chronic tonsillar conditions. These patients served as a control group, as
      they did not have a clinically apparent infection at the time of surgery. Only
      HSV-1 (5/80, 6.3%), adenovirus (11/80, 13.8%), and EBV (71/80, 88.8%) were
      detected in our study population. There was no statistically significant
      difference in the frequency of these viruses across different diagnostic groups.
      Quantification of EBV load demonstrated no differences between the PTA and the
      elective tonsillectomy group, nor between the abscessed and non-abscessed tonsil
      of PTA patients. In summary, our data do not support a significant role for the
      examined viruses in the pathogenesis of PTA.

PMID- 22373897
TI  - Ecotoxicological effects of ciprofloxacin on freshwater species: data integration
      and derivation of toxicity thresholds for risk assessment.
AB  - Although antibiotics have been increasingly used and detected in natural samples,
      their ecotoxicological effects on aquatic wildlife are not yet extensively
      studied. Considering the environmental threat posed by the biological activity of
      antibiotics it is quite relevant to assess the resulting impact, especially on
      sub-lethal endpoints. As such, this study evaluated the effects of ciprofloxacin
      on Pseudokirchneriella subcapitata and Lemna minor growth, on the survival and
      reproduction of Daphnia magna and on Gambusia holbrooki survival. The risks
      associated with ciprofloxacin effects on non-target organisms were quantified
      through the calculation of the PEC/PNEC ratio. Overall, the toxicity values
      obtained (at the mg L(-1) level) were higher than the environmental
      concentrations. P. subcapitata and L. minor were more sensitive under short-term
      exposures than D. magna and G. holbrooki. No acute toxicity was observed for
      fish. The chronic assay with D. magna evidenced that long term exposures to lower
      concentrations of this antibiotic induced impairments on its life-history
      parameters. Such outcome may pre-empt potential damages on the long-term
      maintenance of natural populations continuously exposed to the input of
      antibiotics. Indeed, the PEC/PNEC ratios showed that ciprofloxacin represents a
      risk for the most sensitive aquatic organisms, since the defined threshold of an
      acceptable risk was considerably surpassed.

PMID- 22373898
TI  - An esophageal probe for measuring three-dimensional electric fields during
      external cardiac defibrillation.
AB  - External defibrillation is a common treatment for the cardiac arrhythmia atrial
      fibrillation. Electrode placement has been shown to affect defibrillation
      efficacy and required energy levels. We suggest investigating the relationship
      between esophageal electric fields (EEFs) and atrial defibrillation thresholds to
      determine the feasibility of creating patient-specific electrode placements using
      EEFs. This study presents the design and implementation of an esophageal probe
      (EP) that accurately measures three-dimensional electric fields. The root-mean
      square error of the EP was 1.69% as determined by measurements performed in an
      electrolytic tank. The EP also performed well during in vivo testing in a pig.
      There was a strong positive relationship between EEF(2)s and applied energy
      during defibrillation strength shocks. The EEF measurements were also repeatable,
      with less than 4.24% difference between repeated shocks. This is the first
      description of a probe designed specifically for measuring electric fields in the
      esophagus.

PMID- 22373899
TI  - Bilateral subdural intracranial hematoma after accidental dural puncture.

PMID- 22373900
TI  - A novel fluorescent general anesthetic enables imaging of sites of action in
      vivo.

PMID- 22373901
TI  - [Comorbidities and psoriasis. Impact on clinical practice].
AB  - Psoriasis is a genetically determined, chronic inflammatory systemic disease.
      Besides skin symptoms, patients with moderate to severe forms of psoriasis show
      an association with other diseases, referred to as comorbidities. Metabolic
      disorders (e.g. diabetes mellitus, insulin resistance, dyslipidemia mainly in
      obese patients) and cardiovascular diseases (e.g. arterial hypertension, coronary
      artery disease, myocardial infarction and stroke) are of importance as they can
      increase patients' mortality. In addition, psychiatric diseases are more frequent
      in psoriasis patients and influence the therapeutic approach. The dermatologist
      in most cases is the primarily consulted physician for patients with psoriasis
      and therefore plays the role as a gatekeeper managing therapy. He is responsible
      for the early diagnosis of comorbidities and insuring their appropriate
      management. The anti-psoriatic treatment has to be adapted to existing
      comorbidities and their systemic treatments. The following article provides
      information on psoriatic comorbidities and their consequences for daily practice.

PMID- 22373902
TI  - [Skin, bonding and partnership in atopic dermatitis and psoriasis].
AB  - OBJECTIVE: On the basis of attachment, the study combines results in relationship
      and psychosomatic research. A buffering hypothesis of a secure attachment in
      patients with chronic skin diseases is checked. METHODS: Patients with atopic
      dermatitis (n = 21) and psoriasis (n = 22) were tested with various
      questionnaires: the German questionnaire for partnership attributes (PFB) and
      problem list (PL), questionnaire for psychosomatic complaints (BEB), Relationship
      Scales Questionnaire (RSQ), and a self-designed questionnaire. RESULTS:
      Unsecurely attached patients with atopic dermatitis feel mentally more disturbed
      and report more coherence between mental strains and changes in skin surface than
      securely attached psoriasis patients. There are tendencies to the assumed
      buffering effects. The study shows hints of the importance of attachment theory
      in psychosomatic skin diseases. CONCLUSION: In the treatment of patients with
      chronic skin diseases psychosocial aspects should be taken into consideration.
      Partnership factors might be used as a resource.

PMID- 22373903
TI  - Cause and circumstance of in-hospital mortality among patients undergoing
      contemporary percutaneous coronary intervention: a root-cause analysis.
AB  - BACKGROUND: Prior studies suggest that most deaths in patients undergoing
      percutaneous coronary intervention (PCI) are related to procedural complications.
      Mortality associated with PCI has steadily declined during the past decade, and
      the cause and circumstance of death among patients undergoing PCI in the
      contemporary era remain unknown. METHODS AND RESULTS: We evaluated all patients
      undergoing PCI at the University of Michigan from 2001 to 2009. There were 85
      deaths among a total of 5520 patients undergoing PCI during this time period. By
      using a standardized data collection form, 3 cardiologists (2 interventional,
      H.S.G. and D.S.M.; 1 noninvasive, A.M.B.) determined the cause and circumstance
      of death, in addition to grading the preventability of death. Left ventricular
      failure was the most common cause of death (35.3%, n=30), followed by
      neurological compromise (16.5%, n=14) and arrhythmia (12.1%, n=12). The
      circumstance of death was mostly acute cardiac (52.9%, n=45), with a procedural
      complication composing a small fraction (7.1%, n=6). Reviewers determined 93% of
      deaths to be mostly or entirely unpreventable. CONCLUSIONS: Procedural
      complications are responsible for a small fraction of deaths among patients
      undergoing contemporary PCI. Measures to further enhance procedural safety are
      unlikely to translate into meaningful reductions in PCI mortality.

PMID- 22373904
TI  - Health outcomes with catheter ablation or antiarrhythmic drug therapy in atrial
      fibrillation: results of a propensity-matched analysis.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) face significant risks of
      stroke and heart failure. The objective of this study was to determine whether AF
      ablation reduces the long-term risk of stroke or heart failure compared with
      antiarrhythmic drug therapy. METHODS AND RESULTS: A coding algorithm was used to
      identify AF patients treated with catheter ablation (n=3194) or antiarrhythmic
      drugs without ablation (n=6028) between 2005 and 2009 using The MarketScan
      Research Database from Thomson Reuters From this sample, 801 pairs were
      propensity matched, based on 15 demographic and clinical characteristics and
      baseline medication use. Rates of stroke/transient ischemic attack (TIA) and
      heart failure hospitalizations for up to 3 years were examined. Patients treated
      with catheter ablation had a significantly lower rate of stroke or TIA (3.4% per
      year) than a group of patients with AF managed with antiarrhythmic drugs only
      (5.5% per year), with an unadjusted hazard ratio of 0.62 (95% CI, 0.44-0.86;
      P=0.005). The rates for heart failure hospitalization were 1.5% per year in the
      ablation group and 2.2% per year in the antiarrhythmic drug group, with an
      unadjusted hazard ratio of 0.69 (95% CI, 0.42-1.15; P=0.158). These results were
      minimally altered in Cox proportional hazards models, which further adjusted for
      potential confounders not well balanced by the propensity matching. CONCLUSIONS:
      In a large propensity-matched community sample, AF ablation was associated with a
      reduced risk of stroke/TIA and no significant difference in heart failure
      hospitalizations compared with antiarrhythmic drug therapy. These findings
      require confirmation with randomized study designs.

PMID- 22373905
TI  - Regional patterns of use of a medical management strategy for patients with non
      ST-segment elevation acute coronary syndromes: insights from the EARLY ACS Trial.
AB  - BACKGROUND: Regional differences in the profile and prognosis of non-ST-segment
      elevation acute coronary syndrome (NSTE ACS) patients treated with medical
      management after angiography remain uncertain. METHODS AND RESULTS: Using data
      from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute
      Coronary Syndromes (EARLY ACS) trial, we examined regional variations in the use
      of an in-hospital medical management strategy in NSTE ACS patients who had
      significant coronary artery disease (CAD) identified during angiography, factors
      associated with the use of a medical management strategy, and 1-year mortality
      rates. Of 9406 patients, 8387 (89%) underwent angiography and had significant
      CAD; thereafter, 1766 (21%) were treated solely with a medical management
      strategy (range: 18% to 23% across 4 major geographic regions). Factors most
      strongly associated with a medical management strategy were negative baseline
      troponin values, prior coronary artery bypass grafting, lower baseline hemoglobin
      values, and greater number of diseased vessels; region was not a significant
      factor. One-year mortality was higher among patients treated with a medical
      management strategy compared with those who underwent revascularization (7.8%
      versus 3.6%; adjusted hazard ratio, 1.46; 95% CI, 1.21-1.76), with no significant
      interaction by region (interaction probability value=0.42). CONCLUSIONS:
      Approximately 20% of NSTE ACS patients with significant CAD in an international
      trial were treated solely with an in-hospital medical management strategy after
      early angiography, with no regional differences in factors associated with
      medical management or the risk of 1-year mortality. These findings have important
      implications for the conduct of future clinical trials, and highlight global
      similarities in the profile and prognosis of medically managed NSTE ACS patients.

PMID- 22373906
TI  - Improving thromboprophylaxis using atrial fibrillation diagnostic capabilities in
      implantable cardioverter-defibrillators: the multicentre Italian ANGELS of AF
      Project.
AB  - BACKGROUND: Atrial fibrillation (AF) is a well-established risk factor for stroke
      and thromboembolism and is a frequent comorbid arrhythmia in patients with
      implantable cardioverter-defibrillators (ICDs). The Anticoagulation Use
      Evaluation and Life Threatening Events Sentinels (ANGELS) of AF project was a
      medical care program aimed at supporting adherence to oral anticoagulation (OAC)
      guidelines for thromboprophylaxis through the use of ICD AF diagnostics. METHODS
      AND RESULTS: Fifty Italian cardiology clinics followed 3438 patients with ICDs.
      In a subgroup of 15 centers (the ANGELS of AF centers), cardiologists attending
      to follow-up visits were supplied with specific reports describing stroke risk
      factors and risk scores (American College of Chest Physicians and CHADS(2)
      [congestive heart failure, hypertension, age >=75 years, diabetes mellitus, and
      prior stroke or transient ischemic attack]), AF occurrence and duration, and
      current antithrombotic therapy for patients with AF, especially those with a
      CHADS(2) score >0 and not on OAC therapy. The remaining centers represented a
      control group of patients as a comparison of OAC use. In the ANGELS of AF
      centers, 709 (36%) patients had AF described either in their clinical history
      (n=426 [22%]) or as new-onset AF (n=257 [14%]). Among 683 (96%) patients with
      CHADS2 score >0, 209 (30.6%) were not taking an OAC. Appropriate OAC therapy was
      prescribed in 10% (22/209) of patients after evaluation of ANGELS of AF reports.
      The percentage of patients on OAC therapy, as indicated by guidelines, increased
      during follow-up from 46.1% at baseline, to 69.4% at the stroke risk evaluation
      phase, to up to 72.6% at the end of the observation period. In control centers,
      corresponding figures were 46.9% at baseline and 56.8% at the end of the
      observation period (P<0.001 versus ANGELS of AF group). CONCLUSIONS: The ANGELS
      of AF project demonstrates the possibility to improve OAC use in accordance with
      available guidelines for stroke risk reduction in AF by supplying attending
      physicians with reports about patients risk factors and AF information from
      continuous ICD monitoring.

PMID- 22373907
TI  - ChromHMM: automating chromatin-state discovery and characterization.

PMID- 22373909
TI  - Modeling cellular signaling: taking space into the computation.

PMID- 22373910
TI  - Small is beautiful.

PMID- 22373911
TI  - OMERO: flexible, model-driven data management for experimental biology.
AB  - Data-intensive research depends on tools that manage multidimensional,
      heterogeneous datasets. We built OME Remote Objects (OMERO), a software platform
      that enables access to and use of a wide range of biological data. OMERO uses a
      server-based middleware application to provide a unified interface for images,
      matrices and tables. OMERO's design and flexibility have enabled its use for
      light-microscopy, high-content-screening, electron-microscopy and even non-image
      genotype data. OMERO is open-source software, available at
      http://openmicroscopy.org/.

PMID- 22373912
TI  - Adrenal function in cats with hyperthyroidism.
AB  - Adrenal function may be altered in animals with hyperthyroidism. The aim of the
      study was to assess adrenal function of hyperthyroid cats (n = 17) compared to
      healthy cats (n = 18) and cats with chronic diseases (n = 18). Adrenal function
      was evaluated by adrenocorticotropic hormone (ACTH) stimulation test and the
      urinary cortisol to creatinine ratio (UCCR) was determined. Length and width of
      both adrenal glands were measured via ultrasound. Hyperthyroid cats had
      significantly higher cortisol levels before and after stimulation with ACTH than
      the other groups. However, the UCCR was not elevated in hyperthyroid cats. The
      size of the adrenal glands of hyperthyroid cats was not significantly different
      from the size of those of healthy cats. The results indicate that cats with
      hyperthyroidism have a higher cortisol secretory capacity in a hospital setting.
      The normal size of the adrenal glands suggests that cortisol levels may not be
      increased permanently.

PMID- 22373913
TI  - Therapeutic effect of Yokukansan on social isolation-induced aggressive behavior
      of zinc-deficient and pair-fed mice.
AB  - In patients with dementia including Alzheimer's disease, hallucinations,
      agitation/aggression and irritability are known to frequently occur and as
      distressing behavioral and psychological symptoms of dementia (BPSD). On the
      basis of the evidence on clinical efficacy and safety of Yokukansan, a
      traditional Japanese herbal medicine, on BPSD, in the present study, Yokukansan
      was examined in the therapeutic effects on social isolation-induced aggressive
      behavior of zinc-deficient and pair-fed mice. Yokukansan was p.o. administered
      for 7 days as a drinking water to isolated mice fed a zinc-deficient diet for 10
      days, which exhibited aggressive behavior, and isolated pair-fed mice fed a
      control diet of the amount consumed by zinc-deficient mice for 10 days, which
      exhibited aggressive behavior. Aggressive behavior was evaluated by the resident
      intruder test. Yokukansan (312 mg/kg/day) attenuated both aggressive behaviors of
      zinc-deficient and pair-fed mice. Because Yokukansan can suppress abnormal
      glutamatergic neuron activity, MK-801, an N-methyl-D-aspartate (NMDA) receptor
      blocker, and aminooxyacetic acid (AOAA), a gamma-amino butyric acid (GABA)
      transaminase blocker, were also examined in the effects on social isolation
      induced aggressive behavior. MK-801 (0.1 mg/kg) or AOAA (23 mg/kg) was i.p.
      injected into isolated aggressive mice. Thirty minutes later, the resident
      intruder test was performed to evaluate the effect of the drugs. Both drugs
      attenuated aggressive behavior of zinc deficient mice, but not that of pair-fed
      mice. These results suggest that Yokukansan ameliorates social isolation-induced
      aggressive behavior of zinc-deficient and pair-fed mice through the action
      against glutamatergic neurotransmitter system and other neurotransmitter systems.

PMID- 22373914
TI  - Preparation of gentamicin-loaded electrospun coating on titanium implants and a
      study of their properties in vitro.
AB  - PURPOSE: Implant-related infections are disastrous complications in the clinic,
      and there are no effective therapies. In this preliminary study, gentamicin
      loaded coating on titanium implants was prepared using the electrospinning
      technique, and some properties of the coating titanium implants were studied.
      METHODS: We adopted the electrospinning technique to prepare gentamicin-coated
      titanium implants. The surface structure of the coating implants was observed
      using scanning electron microscope. An elution study was performed to determine
      the release behavior of the gentamicin from the coating. The antibacterial
      efficacy and quantitative analysis of the bacterial adhesion of Staphylococcus
      aureus were evaluated in vitro, and the cytotoxicity of the coated titanium
      implants on osteoblasts was investigated in vitro. RESULTS: The morphology of the
      gentamicin-coated titanium implants exhibited nanofibers, and the release of
      gentamicin showed an initial gentamicin burst followed by a slow release. The
      gentamicin-coated titanium implants had a persistent antibacterial efficacy for 1
      week and significantly reduced the adhesion of the Staphylococcus aureus compared
      with bare titanium implants in vitro. There was no cytotoxicity observed in vitro
      for the gentamicin-coated implants. CONCLUSION: The gentamicin-coated titanium
      implants, which were prepared using an electrospinning technique, present many
      advantages and may be considered to prevent and treat the implant-related
      infections.

PMID- 22373915
TI  - Neisseria conserved protein DMP19 is a DNA mimic protein that prevents DNA
      binding to a hypothetical nitrogen-response transcription factor.
AB  - DNA mimic proteins occupy the DNA binding sites of DNA-binding proteins, and
      prevent these sites from being accessed by DNA. We show here that the Neisseria
      conserved hypothetical protein DMP19 acts as a DNA mimic. The crystal structure
      of DMP19 shows a dsDNA-like negative charge distribution on the surface,
      suggesting that this protein should be added to the short list of known DNA mimic
      proteins. The crystal structure of another related protein, NHTF (Neisseria
      hypothetical transcription factor), provides evidence that it is a member of the
      xenobiotic-response element (XRE) family of transcriptional factors. NHTF binds
      to a palindromic DNA sequence containing a 5'-TGTNAN(11)TNACA-3' recognition box
      that controls the expression of an NHTF-related operon in which the conserved
      nitrogen-response protein [i.e. (Protein-PII) uridylyltransferase] is encoded.
      The complementary surface charges between DMP19 and NHTF suggest specific charge
      charge interaction. In a DNA-binding assay, we found that DMP19 can prevent NHTF
      from binding to its DNA-binding sites. Finally, we used an in situ gene
      regulation assay to provide evidence that NHTF is a repressor of its down-stream
      genes and that DMP19 can neutralize this effect. We therefore conclude that the
      interaction of DMP19 and NHTF provides a novel gene regulation mechanism in
      Neisseria spps.

PMID- 22373916
TI  - Structural and functional characterization of interactions involving the Tfb1
      subunit of TFIIH and the NER factor Rad2.
AB  - The general transcription factor IIH (TFIIH) plays crucial roles in transcription
      as part of the pre-initiation complex (PIC) and in DNA repair as part of the
      nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3'
      endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and
      structurally characterized the interaction between the Tfb1 subunit of TFIIH and
      Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several
      segments of the Rad2 spacer region yield yeast with enhanced sensitivity to UV
      irradiation. Isothermal titration calorimetry studies demonstrate that two acidic
      segments of the Rad2 spacer bind to Tfb1PH with nanomolar affinity. Structure
      determination of a Rad2-Tfb1PH complex indicates that Rad2 binds to TFIIH using a
      similar motif as TFIIEalpha uses to bind TFIIH in the PIC. Together, these
      results provide a mechanistic bridge between the role of TFIIH in transcription
      and DNA repair.

PMID- 22373917
TI  - Microhomology-mediated DNA strand annealing and elongation by human DNA
      polymerases lambda and beta on normal and repetitive DNA sequences.
AB  - 'Classical' non-homologous end joining (NHEJ), dependent on the Ku70/80 and the
      DNA ligase IV/XRCC4 complexes, is essential for the repair of DNA double-strand
      breaks. Eukaryotic cells possess also an alternative microhomology-mediated end
      joining (MMEJ) mechanism, which is independent from Ku and DNA ligase 4/XRCC4.
      The components of the MMEJ machinery are still largely unknown. Family X DNA
      polymerases (pols) are involved in the classical NHEJ pathway. We have compared
      in this work, the ability of human family X DNA pols beta, lambda and MU, to
      promote the MMEJ of different model templates with terminal microhomology
      regions. Our results reveal that DNA pol lambda and DNA ligase I are sufficient
      to promote efficient MMEJ repair of broken DNA ends in vitro, and this in the
      absence of auxiliary factors. However, DNA pol beta, not lambda, was more
      efficient in promoting MMEJ of DNA ends containing the (CAG)n triplet repeat
      sequence of the human Huntingtin gene, leading to triplet expansion. The
      checkpoint complex Rad9/Hus1/Rad1 promoted end joining by DNA pol lambda on non
      repetitive sequences, while it limited triplet expansion by DNA pol beta. We
      propose a possible novel role of DNA pol beta in MMEJ, promoting (CAG)n triplet
      repeats instability.

PMID- 22373918
TI  - Genetic recombination in Bacillus subtilis: a division of labor between two
      single-strand DNA-binding proteins.
AB  - We have investigated the structural, biochemical and cellular roles of the two
      single-stranded (ss) DNA-binding proteins from Bacillus subtilis, SsbA and SsbB.
      During transformation, SsbB localizes at the DNA entry pole where it binds and
      protects internalized ssDNA. The 2.8-A resolution structure of SsbB bound to
      ssDNA reveals a similar overall protein architecture and ssDNA-binding surface to
      that of Escherichia coli SSB. SsbA, which binds ssDNA with higher affinity than
      SsbB, co-assembles onto SsbB-coated ssDNA and the two proteins inhibit ssDNA
      binding by the recombinase RecA. During chromosomal transformation, the RecA
      mediators RecO and DprA provide RecA access to ssDNA. Interestingly, RecO
      interaction with ssDNA-bound SsbA helps to dislodge both SsbA and SsbB from the
      DNA more efficiently than if the DNA is coated only with SsbA. Once RecA is
      nucleated onto the ssDNA, RecA filament elongation displaces SsbA and SsbB and
      enables RecA-mediated DNA strand exchange. During plasmid transformation, RecO
      localizes to the entry pole and catalyzes annealing of SsbA- or SsbA/SsbB-coated
      complementary ssDNAs to form duplex DNA with ssDNA tails. Our results provide a
      mechanistic framework for rationalizing the coordinated events modulated by SsbA,
      SsbB and RecO that are crucial for RecA-dependent chromosomal transformation and
      RecA-independent plasmid transformation.

PMID- 22373919
TI  - Engineered zinc finger nickases induce homology-directed repair with reduced
      mutagenic effects.
AB  - Engineered zinc finger nucleases (ZFNs) induce DNA double-strand breaks at
      specific recognition sequences and can promote efficient introduction of desired
      insertions, deletions or substitutions at or near the cut site via homology
      directed repair (HDR) with a double- and/or single-stranded donor DNA template.
      However, mutagenic events caused by error-prone non-homologous end-joining (NHEJ)
      mediated repair are introduced with equal or higher frequency at the nuclease
      cleavage site. Furthermore, unintended mutations can also result from NHEJ
      mediated repair of off-target nuclease cleavage sites. Here, we describe a simple
      and general method for converting engineered ZFNs into zinc finger nickases
      (ZFNickases) by inactivating the catalytic activity of one monomer in a ZFN
      dimer. ZFNickases show robust strand-specific nicking activity in vitro. In
      addition, we demonstrate that ZFNickases can stimulate HDR at their nicking site
      in human cells, albeit at a lower frequency than by the ZFNs from which they were
      derived. Finally, we find that ZFNickases appear to induce greatly reduced levels
      of mutagenic NHEJ at their target nicking site. ZFNickases thus provide a
      promising means for inducing HDR-mediated gene modifications while reducing
      unwanted mutagenesis caused by error-prone NHEJ.

PMID- 22373920
TI  - Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate
      translation initiation.
AB  - Adaptation to the host cell environment to efficiently take-over the host cell's
      machinery is crucial in particular for small RNA viruses like picornaviruses that
      come with only small RNA genomes and replicate exclusively in the cytosol. Their
      Internal Ribosome Entry Site (IRES) elements are specific RNA structures that
      facilitate the 5' end-independent internal initiation of translation both under
      normal conditions and when the cap-dependent host protein synthesis is shut-down
      in infected cells. A longstanding issue is which host factors play a major role
      in this internal initiation. Here, we show that the functionally most important
      domain V of the poliovirus IRES uses tRNA(Gly) anticodon stem-loop mimicry to
      recruit glycyl-tRNA synthetase (GARS) to the apical part of domain V, adjacent to
      the binding site of the key initiation factor eIF4G. The binding of GARS promotes
      the accommodation of the initiation region of the IRES in the mRNA binding site
      of the ribosome, thereby greatly enhancing the activity of the IRES at the step
      of the 48S initiation complex formation. Moonlighting functions of GARS that may
      be additionally needed for other events of the virus-host cell interaction are
      discussed.

PMID- 22373921
TI  - The high-resolution crystal structure of a parallel intermolecular DNA G-4
      quadruplex/drug complex employing syn glycosyl linkages.
AB  - We have determined the X-ray structure of the complex between the DNA quadruplex
      d(5'-GGGG-3')(4) and daunomycin, as a potential model for studying drug-telomere
      interactions. The structure was solved at 1.08 A by direct methods in space group
      I4. The asymmetric unit comprises a linear arrangement of one d(GGGG) strand,
      four daunomycin molecules, a second d(GGGG) strand facing in the opposite
      direction to the first, and Na and Mg cations. The crystallographic 4-fold axis
      generates the biological unit, which is a 12-layered structure comprising two
      sets of four guanine layers, with four layers each of four daunomycins stacked
      between the 5' faces of the two quadruplexes. The daunomycin layers fall into two
      groups which are novel in their mode of self assembly. The only contacts between
      daunomycin molecules within any one of these layers are van der Waals
      interactions, however there is substantial pi-pi stacking between successive
      daunomycin layers and also with adjacent guanine layers. The structure differs
      significantly from all other parallel d(TGGGGT)(4) quadruplexes in that the 5'
      guanine adopts the unusual syn glycosyl linkage, refuting the widespread belief
      that such conformations should all be anti. In contrast to the related
      d(TGGGGT)/daunomycin complex, there are no ligand-quadruplex groove insertion
      interactions.

PMID- 22373922
TI  - Comparison of microfluidic digital PCR and conventional quantitative PCR for
      measuring copy number variation.
AB  - One of the benefits of Digital PCR (dPCR) is the potential for unparalleled
      precision enabling smaller fold change measurements. An example of an assessment
      that could benefit from such improved precision is the measurement of tumour
      associated copy number variation (CNV) in the cell free DNA (cfDNA) fraction of
      patient blood plasma. To investigate the potential precision of dPCR and compare
      it with the established technique of quantitative PCR (qPCR), we used breast
      cancer cell lines to investigate HER2 gene amplification and modelled a range of
      different CNVs. We showed that, with equal experimental replication, dPCR could
      measure a smaller CNV than qPCR. As dPCR precision is directly dependent upon
      both the number of replicate measurements and the template concentration, we also
      developed a method to assist the design of dPCR experiments for measuring CNV.
      Using an existing model (based on Poisson and binomial distributions) to derive
      an expression for the variance inherent in dPCR, we produced a power calculation
      to define the experimental size required to reliably detect a given fold change
      at a given template concentration. This work will facilitate any future
      translation of dPCR to key diagnostic applications, such as cancer diagnostics
      and analysis of cfDNA.

PMID- 22373923
TI  - Co-evolution of segregation guide DNA motifs and the FtsK translocase in
      bacteria: identification of the atypical Lactococcus lactis KOPS motif.
AB  - Bacteria use the global bipolarization of their chromosomes into replichores to
      control the dynamics and segregation of their genome during the cell cycle. This
      involves the control of protein activities by recognition of specific short DNA
      motifs whose orientation along the chromosome is highly skewed. The KOPS motifs
      act in chromosome segregation by orienting the activity of the FtsK DNA
      translocase towards the terminal replichore junction. KOPS motifs have been
      identified in gamma-Proteobacteria and in Bacillus subtilis as closely related G
      rich octamers. We have identified the KOPS motif of Lactococcus lactis, a model
      bacteria of the Streptococcaceae family harbouring a compact and low GC% genome.
      This motif, 5'-GAAGAAG-3, was predicted in silico using the occurrence and skew
      characteristics of known KOPS motifs. We show that it is specifically recognized
      by L. lactis FtsK in vitro and controls its activity in vivo. L. lactis KOPS is
      thus an A-rich heptamer motif. Our results show that KOPS-controlled chromosome
      segregation is conserved in Streptococcaceae but that KOPS may show important
      variation in sequence and length between bacterial families. This suggests that
      FtsK adapts to its host genome by selecting motifs with convenient occurrence
      frequencies and orientation skews to orient its activity.

PMID- 22373924
TI  - DNA looping by FokI: the impact of twisting and bending rigidity on protein
      induced looping dynamics.
AB  - Protein-induced DNA looping is crucial for many genetic processes such as
      transcription, gene regulation and DNA replication. Here, we use tethered
      particle motion to examine the impact of DNA bending and twisting rigidity on
      loop capture and release, using the restriction endonuclease FokI as a test
      system. To cleave DNA efficiently, FokI bridges two copies of an asymmetric
      sequence, invariably aligning the sites in parallel. On account of the fixed
      alignment, the topology of the DNA loop is set by the orientation of the sites
      along the DNA. We show that both the separation of the FokI sites and their
      orientation, altering, respectively, the twisting and the bending of the DNA
      needed to juxtapose the sites, have profound effects on the dynamics of the
      looping interaction. Surprisingly, the presence of a nick within the loop does
      not affect the observed rigidity of the DNA. In contrast, the introduction of a 4
      nt gap fully relaxes all of the torque present in the system but does not
      necessarily enhance loop stability. FokI therefore employs torque to stabilise
      its DNA-looping interaction by acting as a 'torsional' catch bond.

PMID- 22373925
TI  - Replication fork movement and methylation govern SeqA binding to the Escherichia
      coli chromosome.
AB  - In Escherichia coli, the SeqA protein binds specifically to GATC sequences which
      are methylated on the A of the old strand but not on the new strand. Such
      hemimethylated DNA is produced by progression of the replication forks and lasts
      until Dam methyltransferase methylates the new strand. It is therefore believed
      that a region of hemimethylated DNA covered by SeqA follows the replication fork.
      We show that this is, indeed, the case by using global ChIP on Chip analysis of
      SeqA in cells synchronized regarding DNA replication. To assess hemimethylation,
      we developed the first genome-wide method for methylation analysis in bacteria.
      Since loss of the SeqA protein affects growth rate only during rapid growth when
      cells contain multiple replication forks, a comparison of rapid and slow growth
      was performed. In cells with six replication forks per chromosome, the two old
      forks were found to bind surprisingly little SeqA protein. Cell cycle analysis
      showed that loss of SeqA from the old forks did not occur at initiation of the
      new forks, but instead occurs at a time point coinciding with the end of SeqA
      dependent origin sequestration. The finding suggests simultaneous origin de
      sequestration and loss of SeqA from old replication forks.

PMID- 22373926
TI  - Global or local? Predicting secondary structure and accessibility in mRNAs.
AB  - Determining the structural properties of mRNA is key to understanding vital post
      transcriptional processes. As experimental data on mRNA structure are scarce,
      accurate structure prediction is required to characterize RNA regulatory
      mechanisms. Although various structure prediction approaches are available, it is
      often unclear which to choose and how to set their parameters. Furthermore, no
      standard measure to compare predictions of local structure exists. We assessed
      the performance of different methods using two types of data: transcriptome-wide
      enzymatic probing information and a large, curated set of cis-regulatory
      elements. To compare the approaches, we introduced structure accuracy, a measure
      that is applicable to both global and local methods. Our results showed that
      local folding was more accurate than the classic global approach. We investigated
      how the locality parameters, maximum base pair span and window size, influenced
      the prediction performance. A span of 150 provided a reasonable balance between
      maximizing the number of accurately predicted base pairs, while minimizing
      effects of incorrect long-range predictions. We characterized the error at
      artificial sequence ends, which we reduced by setting the window size
      sufficiently greater than the maximum span. Our method, LocalFold, diminished all
      border effects and produced the most robust performance.

PMID- 22373927
TI  - Prior cognitive activity implicitly modulates subsequent emotional responses to
      subliminally presented emotional stimuli.
AB  - It has been reported that engagement in several kinds of cognitive activity can
      successfully inhibit unpleasant emotions. In this study, we tried to replicate
      the previous finding that cognitive activity can modulate subsequent
      psychological and physiological emotional processes and to investigate whether
      prior cognitive activity can attenuate implicit emotional processes triggered by
      subliminal emotional stimuli. Sixty students were randomly divided into three
      groups (cognitive task group, noncognitive task group, control group). The
      cognitive task group was asked to engage in an n-back task, while the control
      group was asked to stay calm. The noncognitive task group was asked to do a
      handgrip-squeezing task. All participants then engaged in a version of a
      subliminal affective priming task where they were unconsciously exposed to
      affectively negative pictures. The cognitive task group showed lower negative
      experiences after the subliminal affective priming task and a substantial
      reduction in their heart rate responses, as compared with the other groups. These
      results provide evidence that engagement in cognitive activity can attenuate
      emotional processes in an automatic and unconscious manner.

PMID- 22373928
TI  - Effect of feed strategy on methane production and performance of an AnSBBR
      treating effluent from biodiesel production.
AB  - The aim of this work was to investigate the effect of different feeding times (2,
      4 and 6 h) and applied volumetric organic loads (4.5, 6.0 and 7.5 gCOD L(-1) day(
      1)) on the performance of an anaerobic sequencing batch biofilm reactor (AnSBBR)
      treating effluent from biodiesel production. Polyurethane foam cubes were used as
      inert support in the reactor, and mixing was accomplished by recirculating the
      liquid phase. The effect of feeding time on reactor performance showed to be more
      pronounced at higher values of applied volumetric organic loads (AVOLs). Highest
      organic material removal efficiencies achieved at AVOL of 4.5 gCOD L(-1) day(-1)
      were 87 % at 4-h feeding against 84 % at 2-h and 6-h feeding. At AVOL of 6.0 gCOD
      L(-1) day(-1), highest organic material removal efficiencies achieved with 4-h
      and 6-h feeding were 84 %, against 71 % at 2-h feeding. At AVOL of 7.5 gCOD L(-1)
      day(-1), organic material removal efficiency achieved with 4-h feeding was 77 %.
      Hence, longer feeding times favored minimization of total volatile acids
      concentration during the cycle as well as in the effluent, guaranteeing process
      stability and safety.

PMID- 22373929
TI  - Comparison of two techniques for diagnosis of cryptosporidiosis in diarrhoeic
      goat kids and lambs in Cyprus.
AB  - This study was conducted in the Larnaca area of Cyprus and included 28 goat and
      15 sheep flocks suffering from neonatal diarrhoea (>20%). Faecal samples from
      diarrhoeic animals revealed that 25 of the 28 goat and 12 of the 15 sheep flocks
      were positive for Cryptosporidium. The ELISA was more accurate in the diagnosis
      of cryptosporidiosis compared to the Ziehl-Neelsen staining technique (P < 0.05).
      Flock size and the period of kidding/lambing were found to be the main risk
      factors implicated in the occurrence of neonatal goat kid/lamb cryptosporidiosis.

PMID- 22373930
TI  - Effect of bypass fat supplementation on productive performance and blood
      biochemical profile in lactating Murrah (Bubalus bubalis) buffaloes.
AB  - The study investigated the effect of dietary supplementation of bypass fat on
      productive performance and blood biochemical profile of lactating Murrah
      buffaloes (Bubalus bubalis). Fifteen multiparous buffaloes (2-4 lactation) of
      early to mid lactation were divided in three homogenous groups T(1) (control),
      T(2), and T(3) of five each. The animals in T(1) were fed with a basal diet
      consisting of a concentrate mixture, green sorghum, and wheat straw as per
      requirements, while the animals in group T(2) and T(3) were fed with same ration
      supplemented with 0.7 % (100 g/day) and 1.4 % (200 g/day) bypass fat (on dry
      matter intake (DMI) basis), respectively. The feed intake, milk yield, and milk
      composition were not influenced by supplemental bypass fat. However, fat
      corrected milk (6.5 %) yield was higher (P < 0.05) in T(3) (14.21) than that of
      T(1) (9.83) and similar with T(2) (11.05). Feed efficiency (milk yield/kg DMI)
      was higher (P < 0.05) in group T(3) (0.51) than that of T(1) (0.38) and T(2)
      (0.41) indicating that buffaloes fed with bypass fat which is 1.4 % (200 g/day)
      of the diet were economically more efficient. The serum cholesterol level was
      higher (P < 0.01) in bypass fat-supplemented group (T(2) and T(3)) of animals.
      Serum high density lipoprotein (HDL) cholesterol (good cholesterol) level was
      more (P < 0.05) than LDL cholesterol (bad cholesterol) level with higher dose of
      bypass fat in T(3) than T(2). It was concluded that bypass fat supplementation
      with 1.4 % of the diet (200 g/day) increased the fat-corrected milk production
      and feed efficiency along with serum HDL cholesterol level in lactating Murrah
      buffaloes.

PMID- 22373931
TI  - Generation of fuel from CO2 saturated liquids using a p-Si nanowire || n-TiO2
      nanotube array photoelectrochemical cell.
AB  - Light-driven, electrically biased pn junction photoelectrochemical (PEC) cells
      immersed in an electrolyte of CO(2) saturated 1.0 M NaHCO(3) are investigated for
      use in generating hydrocarbon fuels. The PEC photocathode is comprised of p-type
      Si nanowire arrays, with and without copper sensitization, while the photoanode
      is comprised of n-type TiO(2) nanotube array films. Under band gap illumination,
      the PEC cells convert CO(2) into hydrocarbon fuels, such as methane, along with
      carbon monoxide and substantial rates of hydrogen generation due to water
      photoelectrolysis. In addition to traces of C3-C4 hydrocarbons, methane and
      ethylene were formed at the combined rate of 201.5 nM/cm(2)-hr at an applied
      potential of -1.5 V vs. Ag/AgCl. The described technique provides a unique
      approach, utilizing earth abundant materials, for the photocatalytic reduction of
      CO(2) with subsequent generation of higher order hydrocarbons and syngas
      constituents of carbon monoxide and hydrogen.

PMID- 22373932
TI  - Pedicle screws can be 4 times stronger than lateral mass screws for insertion in
      the midcervical spine: a biomechanical study on strength of fixation.
AB  - STUDY DESIGN: A biomechanical study. OBJECTIVE: To compare, in cervical vertebrae
      (C3-C6), the pullout strengths of pedicle screws and lateral mass screws after
      both types of screw had been subjected to a period of cyclic loading in 2 planes.
      SUMMARY OF BACKGROUND DATA: In posterior subaxial cervical fixation systems,
      screws are usually inserted into the lateral mass. As an alternative to lateral
      mass fixation, pedicle screw fixation became popular in the 1990s and was first
      used for lower cervical spine trauma cases. However, it is controversial as to
      whether lateral mass screw fixation in the upper-middle cervical spine offers as
      much biomechanical security as compared with pedicle screw fixation. METHODS: For
      each of the 32 vertebrae, 1 side was randomly chosen to receive a pedicle screw
      and the other side a lateral mass screw. The pedicle or lateral mass screws
      inserted into the first 16 vertebrae were cyclically loaded to simulate torsion
      and the remaining 16 vertebrae were cyclically loaded to simulate
      flexion/extension of the spine. At the end of the cyclic loading each screw was
      pulled out along its long axis. RESULTS: For the torsion group, the mean pullout
      strength of the pedicle screws was nearly 4 times greater than the mean pullout
      strength of the lateral mass screws (cf 762 N with 191 N). In contrast, the mean
      pullout strength of the pedicle screws in the flexion/extension group was only
      twice the mean pullout strength of the lateral mass screws (cf 571 N with 289 N).
      CONCLUSIONS: Not forgetting the potential risks of inserting pedicle screws in
      cervical vertebrae, pedicle screws are a better biomechanical choice than lateral
      mass screws for cervical fixation at the levels C3 through to C6.

PMID- 22373933
TI  - Factors that affect functional capacity in patients with musculoskeletal pain: a
      Delphi study among scientists, clinicians, and patients.
AB  - OBJECTIVE: To reach consensus on the most important biopsychosocial factors that
      influence functional capacity results in patients with chronic nonspecific
      musculoskeletal pain, arranged in the framework of the International
      Classification of Functioning, Disability and Health. DESIGN: Three-round,
      internet-based Delphi survey. SETTING: Not applicable. PARTICIPANTS: Participants
      were scientists, clinicians, and patients familiar with functional capacity
      testing. Scientists were invited through purposive sampling based on the number
      of relevant publications in peer-reviewed journals. The scientists recruited
      clinicians and patients through snowball sampling. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Consensus was reached if at least moderate influence (25%)
      was achieved and an interquartile range of no more than 1 point was reached.
      RESULTS: Thirty-three scientists, 21 clinicians, and 21 patients from 9 countries
      participated. Participants reached consensus on 6 factors that can influence the
      outcome of the lifting test, having a median of severe influence (50%-95%):
      catastrophic thoughts and fear, patient adherence to "doctor's orders," internal
      and external motivation, muscle power, chronic pain behavior, and avoidance
      behavior. Motivation, chronic pain behavior, and sensation of pain were the top 3
      factors affecting postural tolerance and repetitive movement functional capacity
      tests. Furthermore, participants reported 28 factors having a median of moderate
      influence (25%-49%) that could influence the outcome of lifting, postural
      tolerance, and repetitive movement tests. CONCLUSIONS: Overall, chronic pain
      behavior, motivation, and sensation of pain are the main factors that can
      influence functional capacity results. We recommend that scientists and
      clinicians, respectively, consider the most important factors when planning
      future studies and when interpreting functional capacity test results.

PMID- 22373934
TI  - The use of pedometers in stroke survivors: are they feasible and how well do they
      detect steps?
AB  - OBJECTIVES: To determine (1) the feasibility of pedometers for stroke patients
      and (2) the level of agreement between pedometers and actual step count. DESIGN:
      Observational agreement study. SETTING: Six stroke units. PARTICIPANTS:
      Independently mobile stroke patients (N=50) ready for hospital discharge.
      INTERVENTIONS: Patients were asked to apply 3 pedometers: 1 around the neck and 1
      above each hip. Patients performed a short walk lasting 20 seconds, then a 6
      minute walk test 6MWT. Video recordings determined the criterion standard step
      count. MAIN OUTCOME MEASURE: Agreement between the step count recorded by
      pedometers and the step count recorded by viewing the criterion standard video
      recordings of the 2 walks. RESULTS: Five patients (10%) needed assistance to put
      on the pedometers, and 5 (10%) could not read the step count. Thirty-nine (78%)
      would use pedometers again. Below a gait speed of about 0.5 m/s, pedometers did
      not generally detect steps. Agreement analyses showed that even above 0.5 m/s,
      pedometers undercounted steps for both the short walk and 6MWT; for example, the
      mean difference between the video recorder and pedometer around the neck was 5.93
      steps during the short walk and 32.4 steps during the 6MWT. CONCLUSIONS:
      Pedometers are feasible but generally do not detect steps at gait speeds below
      about 0.5 m/s, and they undercount steps at gait speeds above 0.5 m/s.

PMID- 22373935
TI  - Validity of submaximal exercise testing in adults with athetospastic cerebral
      palsy.
AB  - OBJECTIVE: To examine the validity of the multistage submaximal cycle ergometer
      test for adults with athetospastic cerebral palsy. DESIGN: Cross-sectional and
      correlative study. Oxygen uptake and heart rates were recorded while the
      participants underwent the maximal cycle ergometer test and the multistage
      submaximal cycle ergometer test. Peak oxygen consumption (Vo(2)peak) was achieved
      by the maximal cycle test. Maximum oxygen consumption (VO(2)max) was predicted by
      the multistage submaximal cycle ergometer test. SETTING: Research laboratory
      setting. PARTICIPANTS: Adults with athetospastic cerebral palsy (N=16; 10 women
      and 6 men; mean age +/- SD, 43.7+/-14.5y). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Peak VO(2) was compared with the predicted VO(2)max. RESULTS:
      Mean VO(2)peak and the predicted VO(2)max +/- SD were 866.9+/-202.9 mL/min(-1)
      and 857.4+/-248.4 mL/min(-1), respectively. There was not a significant
      difference between VO(2)peak values and the predicted VO(2)max values (r=.28).
      And there was a significant correlation between VO(2)peak values and the
      predicted VO(2)max values (r=.94, P<.001). SE of the estimate (or SE for X to Y)
      was 71.2 mL/min(-1), equivalent to 7.4%. CONCLUSIONS: The multistage submaximal
      cycle ergometer test may provide a valid VO(2)max estimate of adults with
      athetospastic cerebral palsy.

PMID- 22373936
TI  - Effect of fracture type on health-related quality of life among older women in
      Taiwan.
AB  - OBJECTIVE: To investigate changes in health-related quality of life (HRQOL)
      during the first year after injury in elderly Taiwanese women who had fractured a
      hip, vertebra, distal forearm, or multiple sites. DESIGN: Longitudinal cohort
      study. SETTING: Personal or telephone interviews of patients from 3 teaching
      hospitals. PARTICIPANTS: Women (N=347; mean age +/- SD, 78.0+/-6.6y) who had
      sustained a fracture of the hip, vertebra, or distal forearm due to a fall
      participated in the baseline assessment, in which both current and prefracture
      HRQOL data were collected. At 6 and 12 months after the fracture, 285 and 254
      women, respectively, completed the follow-up assessments. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The 4 domains of physical capacity,
      psychological well-being, social relationships, and environment of the brief
      version of the World Health Organization Quality of Life questionnaire were
      assessed. RESULTS: After adjusting for prefracture HRQOL scores and baseline
      characteristics, women with a hip fracture showed a significant improvement in
      physical capacity (3.5 points) and a significant decline in social relationships
      (-3.7 points). Relative to women with a hip fracture at 12 months after injury,
      those with a vertebral fracture exhibited significantly greater improvement (5.2
      points) in physical capacity; those with a distal forearm fracture had
      significantly greater improvements in physical capacity (11.5 points),
      psychological well-being (8.4 points), social relationships (7.2 points), and
      environment (10.9 points), while those with multiple fractures displayed
      significantly greater improvement in physical capacity (16.5 points),
      psychological well-being (13.3 points), and environment (10.3 points).
      CONCLUSIONS: Among the 4 fracture types in elderly women, hip fractures may
      result in the smallest improvement in the physical domain and the greatest
      declines in the psychological, social, and environmental domains during the first
      year. The magnitude of the impact of each fracture type varied across different
      domains.

PMID- 22373937
TI  - Immediate effects of a new microprocessor-controlled prosthetic knee joint: a
      comparative biomechanical evaluation.
AB  - OBJECTIVE: To investigate the immediate biomechanical effects after transition to
      a new microprocessor-controlled prosthetic knee joint. DESIGN: Intervention cross
      over study with repeated measures. Only prosthetic knee joints were changed.
      SETTING: Motion analysis laboratory. PARTICIPANTS: Men (N=11; mean age +/- SD,
      36.7+/-10.2y; Medicare functional classification level, 3-4) with unilateral
      transfemoral amputation. INTERVENTIONS: Two microprocessor-controlled prosthetic
      knee joints: C-Leg and a new prosthetic knee joint, Genium. MAIN OUTCOME
      MEASURES: Static prosthetic alignment, time-distance parameters, kinematic and
      kinetic parameters, and center of pressure. RESULTS: After a half-day training
      and an additional half-day accommodation, improved biomechanical outcomes were
      demonstrated by the Genium: lower ground reaction forces at weight acceptance
      during level walking at various velocities, increased swing phase flexion angles
      during walking on a ramp, and level walking with small steps. Maximum knee
      flexion angle during swing phase at various velocities was nearly equal for
      Genium. Step-over-step stair ascent with the Genium knee was more physiologic as
      demonstrated by a more equal load distribution between the prosthetic and
      contralateral sides and a more natural gait pattern. When descending stairs and
      ramps, knee flexion moments with the Genium tended to increase. During quiet
      stance on a decline, subjects using Genium accepted higher loading of the
      prosthetic side knee joint, thus reducing same side hip joint loading as well as
      postural sway. CONCLUSIONS: In comparision to the C-Leg, the Genium demonstrated
      immediate biomechanical advantages during various daily ambulatory activities,
      which may lead to an increase in range and diversity of activity of people with
      above-knee amputations. Results showed that use of the Genium facilitated more
      natural gait biomechanics and load distribution throughout the affected and sound
      musculoskeletal structure. This was observed during quiet stance on a decline,
      walking on level ground, and walking up and down ramps and stairs.

PMID- 22373938
TI  - Effect of membrane dialysis on characteristics of lyophilised chitosan wafers for
      potential buccal delivery of proteins.
AB  - The effect of membrane dialysis on the characteristics of chitosan based
      lyophilised wafers was investigated. Gels loaded with BSA, glycerol and d
      mannitol were lyophilised with or without membrane dialysis and characterised by
      X-ray diffraction, attenuated total reflectance Fourier transform infra red
      spectroscopy, circular dichroism, scanning electron microscopy, hydration
      capacity, in vitro mucoadhesivity and drug dissolution. The dialysed wafers
      demonstrated enhanced mucoadhesion and drug release properties while newly formed
      sodium acetate in the undialysed wafers caused increased crystallinity with poor
      mucoadhesion and drug release properties. Removal of sodium acetate by membrane
      dialysis is essential for obtaining optimised wafers for potential application to
      the buccal mucosa surface.

PMID- 22373939
TI  - Divalent metal phosphonate coordination polymers constructed from a dipiperidine
      based bisphosphonate ligand.
AB  - The ligand 4,4'-dipiperidine-N,N'-bis(methylenephosphonic acid), H(4)L, has been
      reacted with divalent metal salts under solvothermal conditions to yield seven
      new metal phosphonate coordination polymers. The compounds have been
      characterized by elemental analyses and their structures determined by single
      crystal X-ray diffraction. Zn(2)(L)(H(2)O)(2) and Co(2)(L)(H(2)O)(2) have
      (different) layered structures, while Mn(2)(L)(H(2)O)(3) has a chain motif. In
      these compounds, the N atoms of the ligand bind to the metal ions. alpha
      Co(2)Cl(2)(H(2)L), formed from CoCl(2).6H(2)O and H(4)L in ethanol, is also
      layered but the N atoms of the ligand are protonated. The Co atoms are
      tetrahedral, coordinated by three phosphonate oxygen atoms and a chloride ion. A
      polymorph of this compound, beta-Co(2)Cl(2)(H(2)L), was obtained from a mixed
      ionic liquid under microwave irradiation. The primary difference between the
      polymorphs is the orientation of the phosphonate group relative to the
      dipiperidine. When reacted hydrothermally with Sn(II)C(2)O(4), H(4)L partially
      decomposes, producing phosphate ions which are incorporated into the structure of
      Sn(6)O(2)(H(2)L)(PO(4))(2).4H(2)O. In this compound, the N atoms of the ligand
      are protonated, and two oxide anions are incorporated for charge balance. A
      second phase is obtained from the same reaction, which was determined to be
      Sn(7)O(L)(3). This compound has a layered structure which contains relatively
      large voids within the inorganic portion of the layer. These structures are
      discussed, as well as factors influencing the state of protonation in the final
      compounds. The choice of solvent and temperature were found to have a significant
      influence on the type of structure obtained.

PMID- 22373940
TI  - Identification and sensitivity of two rare fungal species isolated from two
      patients with Fusarium keratomycosis.
AB  - We report two cases of Fusarium keratomycosis in which molecular analysis was
      used to identify two rare causative Fusarium species. A 65-year-old woman was
      diagnosed with Fusarium keratomycosis caused by F. equiseti, confirmed by
      sequencing the internal transcribed spacer (ITS) region and morphological
      characteristics. She was initially treated with topical corticosteroid but the
      keratitis did not improve. Even after aggressive antifungal treatment, there was
      a severe reduction of vision. In the end, the eye perforated. Our second case was
      a 75-year-old man who had diabetes mellitus. He developed keratitis after his
      cornea was injured by corn stalks. The ITS region identified the causative
      organism as F. verticillioides. Unlike the first case, he had good visual
      recovery after early antifungal therapy. Our findings demonstrate that both ITS
      and morphological characteristics can be used to identify the exact Fusarium
      species causing Fusarium keratomycosis. This allowed us to determine the
      sensitivity of these species to antifungal drugs that can be used to treat
      patients with these species of Fusarium.

PMID- 22373941
TI  - Effects of sustained administration of quetiapine alone and in combination with a
      serotonin reuptake inhibitor on norepinephrine and serotonin transmission.
AB  - Quetiapine is now used in the treatment of unipolar and bipolar disorders, both
      alone and in combination with other medications. In the current study, the
      sustained administration of quetiapine and N-Desalkyl quetiapine (NQuet) in rats
      in a 3 : 1 mixture (hQuetiapine (hQuet)) was used to mimic quetiapine exposure in
      patients because rats do not produce the latter important metabolite of
      quetiapine. Sustained administration of hQuet for 2 and 14 days, respectively,
      significantly enhanced the firing rate of norepinephrine (NE) neurons by blocking
      the cell body alpha2-adrenergic autoreceptors on NE neurons, whether it was given
      alone or with a serotonin (5-HT) reuptake inhibitor. The 14-day regimen of hQuet
      enhanced the tonic activation of postsynaptic alpha2- but not alpha1-adrenergic
      receptors in the hippocampus. This increase in NE transmission was attributable
      to increased firing of NE neurons, the inhibition of NE reuptake by NQuet, and
      the attenuated function of terminal alpha2-adrenergic receptors on NE terminals.
      Sustained administration of hQuet for 2 and 14 days, respectively, significantly
      inhibited the firing rate of 5-HT, whether it was given alone or with a 5-HT
      reuptake inhibitor, because of the blockade of excitatory alpha1-adrenergic
      receptors on 5-HT neurons. Nevertheless, the 14-day regimen of hQuet enhanced the
      tonic activation of postsynaptic 5-HT(1A) receptors in the hippocampus. This
      increase in 5-HT transmission was attributable to the attenuated inhibitory
      function of the alpha2-adrenergic receptors on 5-HT terminals and possibly to
      direct 5-HT(1A) receptor agonism by NQuet. The enhancement of NE and 5-HT
      transmission by hQuet may contribute to its antidepressant action in mood
      disorders.

PMID- 22373942
TI  - A proof-of-concept randomized controlled study of gabapentin: effects on cannabis
      use, withdrawal and executive function deficits in cannabis-dependent adults.
AB  - There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is
      the most widely used illicit drug in the world, and patients seeking treatment
      for primary cannabis dependence represent 25% of all substance use admissions. We
      conducted a phase IIa proof-of-concept pilot study to examine the safety and
      efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment
      of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled
      clinical trial was conducted in 50 unpaid treatment-seeking male and female
      outpatients, aged 18-65 years, diagnosed with current cannabis dependence.
      Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual
      guided, abstinence-oriented individual counseling was provided weekly to all
      participants. Cannabis use was measured by weekly urine toxicology and by self
      report using the Timeline Followback Interview. Cannabis withdrawal symptoms were
      assessed using the Marijuana Withdrawal Checklist. Executive function was
      measured using subtests from the Delis-Kaplan Executive Function System. Relative
      to placebo, gabapentin significantly reduced cannabis use as measured both by
      urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004),
      and significantly decreased withdrawal symptoms as measured by the Marijuana
      Withdrawal Checklist (p<0.001). Gabapentin was also associated with significantly
      greater improvement in overall performance on tests of executive function
      (p=0.029). This POC pilot study provides preliminary support for the safety and
      efficacy of gabapentin for treatment of cannabis dependence that merits further
      study, and provides an alternative conceptual framework for treatment of
      addiction aimed at restoring homeostasis in brain stress systems that are
      dysregulated in drug dependence and withdrawal.

PMID- 22373943
TI  - Pharmacogenetic association of the galanin receptor (GALR1) SNP rs2717162 with
      smoking cessation.
AB  - Galanin modulates dopaminergic neurotransmission in the mesolimbic dopamine
      system, thereby influencing the rewarding effects of nicotine. Variants in the
      galanin receptor 1 (GALR1) gene have been associated with retrospective craving
      severity and heaviness of smoking in prior research. We investigated
      pharmacogenetic associations of the previously studied GALR1 polymorphism,
      rs2717162, in 1217 smokers of European ancestry who participated in one of three
      pharmacogenetic smoking cessation clinical trials and were treated with nicotine
      patch (n=623), nicotine nasal spray (n=189), bupropion (n=213), or placebo
      (n=192). The primary endpoint was abstinence (7-day point prevalence,
      biochemically confirmed) at the end of treatment. Cravings to smoke were assessed
      on the target quit day (TQD). The longitudinal regression model revealed a
      significant genotype by treatment interaction (P=0.03). There was a reduced odds
      of quitting success with the presence of at least one minor (C) allele in the
      bupropion-treated group (OR=0.43; 95% CI=0.22-0.77; P=0.005) but equivalent quit
      rates by genotype in the nicotine-replacement therapy groups. This genotype by
      treatment interaction was reproduced in a Cox regression model of time to relapse
      (P=0.04). In the bupropion trial, smokers carrying the C allele also reported
      more severe TQD cravings. Further research to identify functional variants in
      GALR1 and to replicate pharmacogenetic associations is warranted.

PMID- 22373945
TI  - The dynamics of bone structure development during pubertal growth.
AB  - The pubertal growth spurt is a time of rapid changes in bone length, mass and
      structure, followed by the cessation of longitudinal growth. The two best studied
      anatomical areas in this respect are the metaphyses and the diaphyses of
      peripheral long bones. A model is presented here in which the speed of
      longitudinal growth and the resulting age gradient in metaphyseal bone are key
      factors in explaining the high incidence of distal radius fractures during
      puberty. As growth in length accelerates, the age of the bone structural elements
      at a given distance to the growth plate decreases, leaving less time for cortical
      thickening through trabecular coalescence. This leads to a discrepancy between
      stagnant metaphyseal bone strength and increasing mechanical requirements in the
      case of accidents. In comparison to the metaphysis, diaphyseal bone develops more
      in line with the increasing mechanical requirements, presumably because the bone
      formation rates needed for diaphyseal growth in width are only a fraction of the
      apposition rates in the metaphysis. It remains largely unexplored how local and
      systemic signals are integrated to achieve site-specific changes in bone
      structure.

PMID- 22373944
TI  - Evidence of IQ-modulated association between ZNF804A gene polymorphism and
      cognitive function in schizophrenia patients.
AB  - ZNF804A gene polymorphism rs1344706 has been suggested as the most compelling
      case of a candidate gene for schizophrenia by a genome-wide association study and
      several replication studies. The current study of 570 schizophrenia patients and
      448 controls again found significantly different genotype frequencies of
      rs1344706 between patients and controls. More important, we found that this
      association was modulated by IQ, with a stronger association among individuals
      with relatively high IQ, which replicated results of Walters et al, 2010. We
      further examined whether this IQ-modulated association also existed between the
      SNP and the intermediate phenotypes (working memory and executive functions) of
      schizophrenia. Data were available from an N-back task (366 patients and 414
      controls) and the attention network task (361 patients and 416 controls). We
      found that the SNP and IQ had significant interaction effects on the intermediate
      phenotypes for patients, but not for controls. The disease risk allele was
      associated with poorer cognitive function in patients with high IQ, but better
      cognitive function in patients with low IQ. Together, these results indicated
      that IQ may modulate the role of rs1344706 in the etiology of both schizophrenia
      and its cognitive impairments, and pointed to the necessity of considering
      general cognitive function as indexed by IQ in the future studies of genetic
      bases of schizophrenia.

PMID- 22373946
TI  - Effect of level of farm mechanization early in life on bone later in life.
AB  - OBJECTIVE: To determine whether an active rural lifestyle during childhood and
      adolescence, defined as low farm mechanization, was associated with bone measures
      later in life. METHODS: DXA bone data from total body, hip and spine, and pQCT
      data from 4% and 20% distal radius were obtained on 330 individuals (157 women)
      aged 20-66 years who farmed at least 75% of their lives. Primary bone outcomes
      included areal bone mineral density (aBMD), aBMD Z-scores, cortical and
      trabecular volumetric BMD, cortical thickness and periosteal circumference.
      Relationship between bone and recall of level of farm mechanization as a child
      was determined after stratifying by sex and controlling for covariates. RESULTS:
      Controlling for covariates, females from low mechanized farms had higher femoral
      neck (FN) bone area (p=0.03) than those on high or moderate mechanized farms. No
      group differences in pQCT ulna measurements or z-scores were found in either
      gender. CONCLUSION: A low farm mechanization level (high physical activity) prior
      to 20 years of age is associated with greater FN bone area in females. Future
      research that includes type and amount of physical activity performed will
      contribute to growing knowledge of how and when regular physical activity during
      childhood and adolescence affects adult bone health.

PMID- 22373948
TI  - Osteogenesis imperfecta: effecting the transition from adolescent to adult
      medical care.
AB  - The objective of this paper is to provide guidelines for pediatricians, adult
      physicians in different medical disciplines and patients' families who are
      planning the transition to adult care for the adolescent with osteogenesis
      imperfecta (OI). This observational report reflects concerns expressed by
      patients, their families, and involved physicians regarding the problems
      encountered with the transition of care. Methods for dealing with transitional
      issues are presented. OI is a heritable disorder of connective tissue in which
      fractures are the dominant clinical feature. However, OI is a systemic disorder
      with broad clinical variability in which there are unpredictable episodes of
      trauma. Coordinated team support provides the best level of care for the child
      with OI. This paper discusses 4 key topics related to effecting the transition
      from pediatric to adult care: 1) Transitioning and maintaining health, 2)
      Preserving or improving the level of function, 3) Assuring continuity of
      medical/surgical care, and 4) Re-structuring psychosocial and work-related
      systems. The process of transition requires active communication between the
      pediatric and adult team members along with a proactive approach by the patient
      and family. In addition, as the transition is established, the patient with OI
      should be encouraged to be his/her own advocate and care coordinator.

PMID- 22373947
TI  - Prednisolone treatment and restricted physical activity further compromise bone
      of mdx mice.
AB  - OBJECTIVES: The purpose of this study was to determine the extent to which
      prednisolone treatment and restricted physical activity caused deleterious
      changes in inherently compromised mdx bone. METHODS: Four week-old male mdx mice
      (n=36) were treated for 8-wk either with or without prednisolone (0.8-1.3
      mg/kg/d) and were housed in traditional or small cages (restricted activity).
      Tibial bone strength, geometry, and intrinsic material properties were assessed
      at the mid-shaft by three-point bending and micro-computed tomography (MUCT).
      RESULTS: Three-point bending results showed that both prednisolone and restricted
      activity reduced bone strength (7%), however stiffness was only reduced in
      restricted-activity mice. MUCT analyses showed that cortical bone area and
      cortical thickness were 13% smaller in restricted-activity mice, and may have
      accounted for their compromised bone strength. Intrinsic material properties,
      including volumetric bone mineral density (vBMD) and modulus of elasticity, were
      not impacted by either treatment, however, vBMD tended to be lower in restricted
      activity mice (p=0.06). CONCLUSIONS: These data show that prednisolone treatment
      and restricted physical activity independently accentuate reductions in the
      strength and geometry of mdx bone, but do not influence intrinsic material
      properties.

PMID- 22373949
TI  - Healing of rat femoral segmental defect with bone morphogenetic protein-2: a dose
      response study.
AB  - OBJECTIVE: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is
      becoming a common clinical approach to enhance bone repair. There is little or no
      information in the literature on the dose of rhBMP-2 required for effective
      healing of critical-sized defects such as those associated with trauma. In this
      study, we used a segmental defect model to assess the dose response of rhBMP-2
      using quantitative and qualitative endpoints. METHODS: Femoral defects in rats
      were replaced with absorbable collagen sponges carrying rhBMP-2 (0, 1, 5, 10 or
      20 MUg; N=5). At 4-weeks new bone formation was assessed using quantitative
      (radiography and microcomputed tomography) and qualitative (histology and
      backscattered-SEM) endpoints statistically compared. RESULTS: rhBMP-2 showed
      increased bridging in the gap. Quantitative evaluation presented a bi-phasic dose
      response curve. Histological assessment revealed that with rhBMP-2 the defect
      showed the presence of spongy bone with the trabeculae layered with active
      osteoblasts and osteoclasts. The density and compactness of the bone varied with
      the dose of rhBMP-2. CONCLUSIONS: Our findings revealed that all doses of rhBMP-2
      result in new bone formation. However, there is an optimum dose of 12 MUg of
      rhBMP-2 for bone repair in this model, above which and below which less
      stimulation of bone occurs.

PMID- 22373950
TI  - 2011 guidelines for the diagnosis and treatment of osteoporosis in Greece.

PMID- 22373951
TI  - Successful surgical treatment of primary hyperparathyroidism during the third
      trimester of pregnancy.

PMID- 22373952
TI  - Different mutation profiles associated to P53 accumulation in colorectal cancer.
AB  - The tumor suppressor TP53 gene is one of the most frequently mutated in different
      types of human cancer. Particularly in colorectal cancer (CRC), it is believed
      that TP53 mutations play a role in the adenoma-carcinoma transition of tumors
      during pathological process. In order to analyze TP53 expressed alleles in CRC,
      we examined TP53 mRNA in tumor samples from 101 patients with sporadic CRC.
      Samples were divided in two groups defined according to whether they exhibit
      positive or negative P53 protein expression as detected by immunohistochemistry
      (IHC). The presence of TP53 mutation was a common event in tumors with an overall
      frequency of 54.5%. By direct sequencing, we report 42 different TP53 sequence
      changes in 55 CRC patients, being two of them validated polymorphisms. TP53
      mutations were more frequent in positive than in negative P53 detection group
      (p<0.0001), being the precise figures 79.6% and 30.8%, respectively. In addition,
      the mutation profiles were also different between the two groups of samples;
      while most of the mutations detected in P53 positive group were missense (38 out
      of 39), changes in P53 negative detection group include 7 insertions/deletions, 6
      missense, 2 nonsense and 1 silent mutation. As previously observed, most
      mutations were concentrated in regions encoding P53 DNA binding domain (DBD).
      Codons 175, 248 and 273 together account for 36.7% of point mutations, in
      agreement with previous observations provided that these codons are considered
      mutation hotspots. Interestingly, we detected two new deletions and two new
      insertions. In addition, in three samples we detected two deletions and one
      insertion that could be explained as putative splicing variants or splicing
      errors.

PMID- 22373953
TI  - Prevention of nutritional rickets in Nigerian children with dietary calcium
      supplementation.
AB  - Nutritional rickets in Nigerian children usually results from dietary calcium
      insufficiency. Typical dietary calcium intakes in African children are about
      200mg daily (approximately 20-28% of US RDAs for age). We sought to determine if
      rickets could be prevented with supplemental calcium or with an indigenous food
      rich in calcium. We enrolled Nigerian children aged 12 to 18months from three
      urban communities. Two communities were assigned calcium, either as calcium
      carbonate (400mg) or ground fish (529+/-109mg) daily, while children in all three
      communities received vitamin A (2500IU) daily as placebo. Serum markers of
      mineral homeostasis and forearm bone density (pDEXA) were measured and
      radiographs were obtained at enrollment and after 18months of supplementation.
      The overall prevalence of radiographic rickets at baseline was 1.2% and of
      vitamin D deficiency [serum 25(OH)D<12ng/ml] 5.4%. Of 647 children enrolled, 390
      completed the 18-month follow-up. Rickets developed in 1, 1, and 2 children
      assigned to the calcium tablet, ground fish, and control groups, respectively
      (approximate incidence 6.4/1000 children/year between 1 and 3years of age).
      Children who developed rickets in the calcium-supplemented groups had less than
      50% adherence. Compared with the group that received no calcium supplementation,
      the groups that received calcium had a greater increase in areal bone density of
      the distal and proximal 1/3 radius and ulna over time (P<0.04). We conclude that
      calcium supplementation increased areal bone density at the radius and ulna, but
      a larger sample size would be required to determine its effect on the incidence
      of rickets.

PMID- 22373954
TI  - Parathyroidectomy leads to decreased blood lead levels in patients with
      refractory secondary hyperparathyroidism.
AB  - OBJECTIVE: Secondary hyperparathyroidism (SHPT) is characterized by high bone
      turnover and may result in increased release of lead (Pb) from bone stores.
      Parathyroidectomy (PTX) drastically changes bone remodeling. This study
      investigated the effects of PTX on the levels of blood lead (blood Pb) in
      patients with refractory SHPT. METHODS: The study included 30 patients on long
      term hemodialysis (HD) who underwent PTX in the nephrology units of two Taiwanese
      hospitals. Changes in serum levels of intact parathyroid hormone (iPTH), bone
      specific alkaline phosphatase (BAP), type 5b tartrate-resistant acid phosphatase
      (TRAP), total calcium (tCa), and blood Pb were analyzed. RESULTS: After PTX,
      serum iPTH was markedly decreased while serum BAP was progressively increased and
      peaked 2weeks after PTX. Serum TRAP levels were progressively decreased during
      the 4week follow-up period. Serum tCa and blood Pb levels decreased sharply
      immediately after PTX. There was a positive correlation between the percentage of
      decrease in tCa and blood Pb at one day after PTX. Further analysis indicated a
      significant positive correlation between levels of blood Pb and serum iPTH
      (r=0.378, p<0.001), blood Pb and serum TRAP (r=0.180, p<0.05), and a negative
      correlation between blood Pb and serum BAP (r=-0.205, p<0.05). CONCLUSION: PTX
      effectively suppressed the elevated levels of blood Pb and serum bone remodeling
      markers, which are common features of SHPT. In addition to decreased Pb release
      from bone, an increased store of Pb in bone may play a role in decreasing serum
      blood Pb levels. These findings suggest that patients undergoing PTX for
      refractory SHPT should strictly avoid environmental exposure to Pb.

PMID- 22373955
TI  - Birthweight and thinness at birth independently predict symptoms of polycystic
      ovary syndrome in adulthood.
AB  - BACKGROUND: The aetiology of polycystic ovary syndrome (PCOS) is unknown and
      contested. While it has been suggested that PCOS could have origins in perturbed
      development, epidemiological findings have been inconclusive. We aimed to examine
      potential fetal origins of PCOS. METHODS: A retrospective birth cohort of 948
      singleton female babies born at one hospital in South Australia in 1973-1975 was
      assembled. Birth characteristics were obtained from hospital records and PCOS
      symptoms were identified through interview and clinical examination when women
      were ~30 years old. Based on the combination of PCOS symptoms, women formed seven
      outcome groups. A multinomial logistic regression analysis was used to
      investigate associations between birth characteristics and these outcome groups.
      RESULTS: After adjusting for gestational age, two distinct birth characteristics
      were associated with two PCOS symptom groups. Each 100 g increase in birthweight
      increased the risk of hyperandrogenism (as a single symptom) in adulthood by 5%
      [relative risk ratio: 1.05, 95% confidence interval (CI): 1.01-1.09]. In
      contrast, each one unit increase in the ponderal index at birth decreased the
      risk of all three key PCOS symptoms (hyperandrogenism, menstrual dysfunction and
      polycystic ovaries) by 21% (0.79, 95% CI: 0.66-0.93). CONCLUSIONS: These results
      suggest two discrete fetal programming pathways (related to high birthweight and
      to thinness at birth) are operating. Our findings point to differing aetiologies
      for symptom clusters, and inform the debate over symptoms that best represent the
      disorder.

PMID- 22373956
TI  - Assessing the suitability of stream water for five different uses and its aquatic
      environment.
AB  - Surface water is one of the essential resources for supporting sustainable
      development. The suitability of such water for a given use depends both on the
      available quantity and tolerable quality. Temporary status for a surface water
      quality has been identified extensively. Still the suitability of the water for
      different purposes needs to be verified. This study proposes a water quality
      evaluation system to assess the aptitude of the Selangor River water for aquatic
      biota, drinking water production, leisure and aquatic sport, irrigation use,
      livestock watering, and aquaculture use. Aptitude of the water has been
      classified in many parts of the river segment as unsuitable for aquatic biota,
      drinking water production, leisure and aquatic sport as well as aquaculture use.
      The water quality aptitude classes of the stream water for nine locations along
      the river are evaluated to contribute to decision support system. The suitability
      of the water for five different uses and its aquatic ecosystem are verified.

PMID- 22373957
TI  - Priming correct information reduces the misinformation effect.
AB  - The misinformation effect is a well-established phenomenon in the false memory
      literature, although the mechanisms that underlie it are debated. In the present
      study, we explored one aspect of the controversy, the fate of the original
      memory. We began from an activation-based view of memory, capitalizing on the
      well-understood processes of associative priming and spreading activation, to
      test the hypothesis that true and suggested information can coexist in memory.
      After exposure to misinformation, participants were unknowingly primed with
      associates of either the true or a suggested item. Misled participants who were
      primed for the true item performed better on a final memory test than did misled
      participants primed for neutral information. The results indicated that true and
      suggested information coexist and that retrieval is influenced by each concept's
      activation level at test. Implications for theories of the misinformation effect
      were discussed.

PMID- 22373958
TI  - The clinical significance of real-time contrast-enhanced ultrasonography in the
      differential diagnosis of breast tumor.
AB  - The objective of this study was to investigate the clinical significance of real
      time contrast-enhanced ultrasonography in the differential diagnosis of breast
      tumor. Fifty-seven breast tumor patients with 63 lesions were studied. Among the
      lesions, 34 are malignant and 29 are benign. A Philips iU-22 ultrasound scanner
      with L12-5 probe was used. Bolus SonoVue was injected via antecubital vein.
      Dynamic imaging was stored and analyzed with QLAB software. Parameters including
      initial time of perfusion (ITP), time to peak (TTP), peak intensity (PI), the
      enhancement pattern and the wash out pattern (WP) of contrast agent were
      observed. Results showed that about 85.3% of the malignant lesions showed
      heterogeneous enhancement and 79.3% of the benign ones showed homogeneous
      enhancement. The persistence time of the contrast agents was clearly longer
      inside the malignant lesion than inside the benign ones. Nevertheless, there were
      no significant differences in the value as ITP and TTP between the malignant and
      the benign lesions, while the PI value of the malignant lesions was significantly
      higher than the benign lesions. This study suggested that real-time contrast
      enhanced ultrasonography is helpful to the differential diagnosis of breast
      tumors; however, the WP of the contrast agent inside the lesion also seems to be
      an important factor.

PMID- 22373959
TI  - Evaluation of the membrane lipid selectivity of the pea defensin Psd1.
AB  - Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum
      seeds, exhibits anti-fungal activity by a poorly understood mechanism of action.
      In this work, the interaction of Psd1 with biomembrane model systems of different
      lipid compositions was assessed by fluorescence spectroscopy. Partition studies
      showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward
      lipid membranes containing ergosterol (the main sterol in fungal membranes) or
      specific glycosphingolipid components, with partition coefficients (K(p))
      reaching uncommonly high values of 10(6). By the opposite, Psd1 does not
      partition to cholesterol-enriched lipid bilayers, such as mammalian cell
      membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity
      loss relative to the wild type. Fluorescence quenching data obtained using
      acrylamide and membrane probes further clarify the mechanism of action of this
      peptide at the molecular level, pointing out the potential therapeutic use of
      Psd1 as a natural antimycotic agent.

PMID- 22373960
TI  - A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4.
AB  - Drawing on converging behavioral, electrophysiological, and imaging evidence, we
      advance an hypothesis for a cognitive phenotype of a SNP in the CHRNA4 gene
      encoding the alpha(4) subunit of alpha(4)beta(2) nicotinic receptors. First, we
      review evidence that visuospatial attention can be decomposed into several
      component processes. Secondly, we consider evidence that one component,
      redirection of attention, is modulated by the nicotinic cholinergic system.
      Third, we review evidence that nicotinic stimulation exerts effects at the
      network level. Fourth, we consider evidence that normal variation in this SNP
      exerts nicotine-like modulatory effects on visuospatial attention. Fifth, we
      hypothesize that the cognitive phenotype of the CHRNA4 rs1044396 SNP is
      characterized by greater ability of T allele carriers to preferentially process
      events in the attentional focus compared to events outside the attentional focus.
      Finally, we consider effects of the CHNRA4 rs1044396 SNP on brain activity and
      cognition in light of our hypothesized cognitive phenotype. This hypothesis makes
      an important contribution to the development of cognitive phenomics by arguing
      for a cognitive phenotype of CHRNA4.

PMID- 22373962
TI  - Evaluation of nasal airway alterations associated with septorhinoplasty by both
      objective and subjective methods.
AB  - The aim of functional septorhinoplasty is to create an esthetically elegant nose
      and harmony in the face by preserving nasal function as well as maintaining or
      restoring adequate airway. Since nasal complaints are usually subjective, it may
      be difficult to evaluate the functions objectively. In the present study, we
      aimed to investigate the alterations in nasal function associated with
      septorhinoplasty by using both objective and subjective methods. The study
      population consisted of 40 patients who underwent septorhinoplasty and 40 healthy
      controls. Before and after the operation, visual analog scale, acoustic
      rhinometry, rhinomanometry, and Odiosoft-Rhino test were applied to all patients
      and controls. There were significant differences in all parameters both before
      and after the operation. While a significant difference was obtained between the
      patient and control groups in terms of preoperative values, no significant
      difference was found between postoperative values of these groups. Both objective
      and subjective methods are important in evaluations.

PMID- 22373963
TI  - Body lift perforator flap breast reconstruction:  a review of 100 flaps in 25
      cases.
AB  - BACKGROUND: Advances in autologous breast reconstruction continue to mount and
      have been fueled most substantially with refinement of perforator flap
      techniques. METHODS: For patients with a desire for autogenous breast
      reconstruction and insufficient abdominal fat for conventional abdominal flaps,
      secondary options such as gluteal perforator flaps or latissimus flaps are
      usually considered. Patients who also have insufficient soft tissue in the
      gluteal donor site and preference to avoid an implant, present a vexing problem.
      The authors describe an option that allows for incorporation of four independent
      perforator flaps for bilateral breast reconstruction when individual donor sites
      are too thin to provide necessary volume. The authors present their experience
      with this technique in 25 patients with 100 individual flaps over 5 years.
      RESULTS: The body lift perforator flap technique, using a layered deep inferior
      epigastric perforator/gluteal perforator flap combination for each breast, was
      performed in this patient set with high success rates and quality aesthetic
      outcomes over several years. Patient satisfaction was high among the studied
      population. CONCLUSIONS: The body lift perforator flap breast reconstruction
      technique can be a reliable, safe, but technically demanding solution for
      patients seeking autogenous breast reconstruction with otherwise inadequate
      individual fatty donor sites. This sophisticated procedure overcomes a limitation
      of autogenous breast reconstruction for these patients that otherwise results in
      a breast with poor projection and overall volume insufficiency. The harvest of
      truncal fat with a circumferential body lift design gives the potential added
      benefit of improved body contour as a complement to this powerful breast
      reconstructive technique. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373964
TI  - Breast reconstruction using a staged nipple-sparing mastectomy following
      mastopexy or reduction.
AB  - BACKGROUND: To address those patients who do not meet anatomical criteria for
      nipple-sparing mastectomy, the authors use a staged approach: (1) mastopexy or
      breast reduction, (2) nipple-sparing mastectomy through the mastopexy incisions
      after a minimum of 3 to 4 weeks, and (3) the final reconstruction. METHODS:
      Fifteen patients underwent nipple-sparing mastectomy at Georgetown University
      Hospital between 2007 and 2010 after planned or unrelated mastopexy or reduction.
      An institutional review board-approved retrospective chart review recorded
      demographic information and outcomes such as skin necrosis and device failure.
      RESULTS: Fifteen patients (24 breasts) underwent nipple-sparing mastectomy after
      mastopexy or reduction with an average follow-up of 13 months. The staged
      procedure was planned in 10 patients [19 breasts (79 percent)] and unplanned, or
      coincidental, in five [five breasts (21 percent)]. The mastectomy was
      prophylactic in 17 breasts (71 percent) and therapeutic in seven (29 percent).
      Four of the 24 operated breasts (17 percent) experienced a complication. Two
      patients [two breasts (8 percent)] developed skin flap necrosis. Two patients
      [three breasts (13 percent)] developed minimal partial nipple-areola complex
      necrosis. One patient [one breast (4 percent)] had an expander explanted for
      infection related to skin flap necrosis. Fourteen patients [23 breasts (96
      percent)] successfully recovered following nipple-sparing mastectomy and prior
      mastopexy or reduction without residual effects of nipple-areola complex or skin
      flap necrosis. CONCLUSIONS: The authors are comfortable offering the staged
      approach to nipple-sparing mastectomy to patients with moderately large or ptotic
      breasts. It may not be suitable for the very large or ptotic breast. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373965
TI  - Free omental flap for partial breast reconstruction after breast-conserving
      surgery.
AB  - Recent advances in endoscopic surgery have allowed laparoscopic harvesting of the
      omental flap with reduced donor-site morbidity and deformity. Between August of
      2004 and May of 2010, the authors performed immediate breast reconstruction with
      the free omental flap in 10 breast cancer patients, employing it either as a
      pedicle flap or as a free flap for volume replacement. Only one complication
      occurred during the follow-up. Cosmetic results were mostly satisfactory. The
      free omental flap is a safe procedure with minimal donor-site morbidity and
      deformity and can be an additional option for immediate partial breast
      reconstruction after breast-conserving surgery. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 22373966
TI  - Local hemodynamic effects of radiation on the rabbit orbitozygomatic complex with
      and without cytoprotection.
AB  - BACKGROUND: The authors have previously demonstrated that radiation-induced
      craniofacial bone growth inhibition may be ameliorated using the known
      cytoprotectant amifostine in the infant rabbit orbitozygomatic complex. The
      authors' hypothesis is that reduction in blood supply plays an important role in
      inhibiting craniofacial bone growth following radiotherapy and that
      cytoprotective pretreatment exerts its protective effect by maintaining blood
      supply. METHODS: Seven-week-old New Zealand male infant rabbits underwent single
      dose orthovoltage irradiation to the right orbitozygomatic complex using
      established protocols: 0 Gy (sham), 35 Gy, and 35 Gy following pretreatment with
      amifostine (300 mg/kg administered intravenously). Blood flow to the
      orbitozygomatic complex, orbitozygomatic complex periosteum, masseter,
      hemimandible, and overlying skin was measured 1, 14, and 63 days after
      irradiation, using the modified 15-MUm radioactive microsphere technique (n = 18
      per group, n = 6 per time point). Orbitozygomatic complex bone specimens were
      harvested for blood vessel morphometry using safranin O stains at days 1 and 100
      after irradiation (n = 20 per group, n = 10 per time point). RESULTS: Blood flow
      to the irradiated orbitozygomatic complex was significantly (p < 0.05) greater 1
      day after single-dose orthovoltage irradiation compared with nonirradiated
      controls. This increase was not observed in the amifostine-pretreated animals and
      was also not seen 14 and 63 days after irradiation. No histomorphometric vessel
      changes were detected at any time point after irradiation in this study.
      CONCLUSIONS: Single-dose orthovoltage irradiation results in a temporary
      elevation in regional blood flow to the orbitozygomatic complex, returning to
      control levels within 14 days. Although pretreatment with amifostine attenuates
      this response, radiation-induced craniofacial bone growth inhibition in this
      model does not appear to be secondary to hemodynamic alterations.

PMID- 22373967
TI  - Discussion: Local hemodynamic effects of radiation on the rabbit orbitozygomatic
      complex with and without cytoprotection.

PMID- 22373961
TI  - APP transgenic mice for modelling behavioural and psychological symptoms of
      dementia (BPSD).
AB  - The discovery of gene mutations responsible for autosomal dominant Alzheimer's
      disease has enabled researchers to reproduce in transgenic mice several hallmarks
      of this disorder, notably Abeta accumulation, though in most cases without
      neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C
      terminal fragments of APP exhibit variations in exploratory activity reminiscent
      of behavioural and psychological symptoms of Alzheimer dementia (BPSD). In
      particular, open-field, spontaneous alternation, and elevated plus-maze tasks as
      well as aggression are modified in several APP transgenic mice relative to non
      transgenic controls. However, depending on the precise murine models, changes in
      open-field and elevated plus-maze exploration occur in either direction, either
      increased or decreased relative to controls. It remains to be determined which
      neurotransmitter changes are responsible for this variability, in particular with
      respect to GABA, 5HT, and dopamine.

PMID- 22373968
TI  - Mapping of lymphosomes in the canine forelimb: comparative anatomy between
      canines and humans.
AB  - BACKGROUND: Breast cancer-related lymphedema is an unsolved iatrogenic dilemma.
      Disfigurement of the affected limb because of increased volume and recurrent
      cellulitis can cause both physical and mental distress for many breast cancer
      survivors. No adequate animal models have been developed to investigate acquired
      lymphedema mimicking breast cancer-related lymphedema, and there is little
      knowledge of the anatomy of the lymphatics in animals. The authors hypothesized
      that a canine forelimb model of the lymphatic system could potentially be used to
      study breast cancer-related lymphedema. METHODS: Six forequarters were used from
      three mongrel hound carcasses. The lymphatic microinjection technique used
      hydrogen peroxide to identify lymphatic vessels. The individual channels were
      injected with a radiopaque lead oxide mixture and recorded on digital
      radiography. Lymphatic territories (lymphosomes) in the canine forelimb were
      demarcated and color coded in accordance with their lymph nodes. The lymphatic
      system in the canine forelimb was compared with that in the human upper
      extremity. RESULTS: The lymphatic system in the canine forelimb was divided into
      two superficial lymphosomes (ventral cervical and axillary) and one deep
      lymphatic system. The ventral cervical lymphosome was larger than the axillary
      lymphosome. A single lymph node in the axilla received fluid from three sites:
      the ventral cranial torso, the superficial medial forelimb, and the deep
      forelimb. The lymphatic systems of the human upper extremity and the canine
      forelimb had some anatomical similarities: distinct superficial and deep system
      and size of the lymphatic vessel. CONCLUSION: The canine model may be a valuable
      animal model for investigating the pathophysiology of upper extremity lymphedema.

PMID- 22373969
TI  - Discussion: Migraine surgery practice patterns and attitudes.

PMID- 22373970
TI  - Health-related quality-of-life assessment and surgical outcomes for auricular
      reconstruction using autologous costal cartilage.
AB  - BACKGROUND: This study aims to assess the health-related quality-of-life benefit
      following auricular reconstruction using autologous costal cartilage in children.
      In addition, key aspects of the surgical reconstruction are assessed. METHODS:
      After auricular reconstruction, patients completed two questionnaires. The first
      was a postinterventional health-related quality-of-life assessment tool, the
      Glasgow Benefit Inventory. A score of 0 signifies no change in health-related
      quality-of-life, +100 indicates maximal improvement, and -100 indicates maximal
      negative impact. The second questionnaire assessed surgical outcomes in auricular
      reconstruction across three areas: facial integration, aesthetic auricular units,
      and costal reconstruction. These were recorded on a five-point ordinal scale and
      are presented as mean scores of a total of 5. RESULTS: The mean total Glasgow
      Benefit Inventory score was 48.1; significant improvements were seen in all three
      Glasgow Benefit Inventory subscales (p < 0.0001). A mean integration score of 3.8
      and a mean aesthetic auricular unit reconstruction score of 3.4 were recorded.
      Skin color matching (4.3) of the ear was most successfully reconstructed and
      auricular cartilage reconstruction scored lowest (3.5). Of the aesthetic units,
      the helix scored highest (3.6) and the tragus/antitragus scored lowest (3.3).
      Donor-site reconstruction scored 3.9. Correlation analysis revealed that higher
      reconstruction scores are associated with a greater health-related quality-of
      life gain (r = 0.5). Ninety-six percent of patients would recommend the procedure
      to a friend. CONCLUSIONS: Auricular reconstruction with autologous cartilage
      results in significant improvements in health-related quality-of-life. In
      addition, better surgical outcomes lead to a greater improvement in health
      related quality-of-life. Comparatively poorer reconstructed areas of the ear were
      identified so that surgical techniques may be improved. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 22373971
TI  - The superior thyroid artery perforator flap:  anatomical study and clinical
      series.
AB  - The redundant tissues of the anterior neck are well suited as a donor site for
      fasciocutaneous flaps in head and neck reconstruction, with similar skin quality
      and numerous underlying perforators. However, historic cadaveric research has
      limited the use of this as a donor site for the design of long and/or large flaps
      for fear of vascular compromise. The authors undertook an anatomical study to
      identify the vascular basis for such flaps and have modified previous designs to
      offer the versatile and reliable superior thyroid artery perforator (STAP) flap.
      Forty-five consecutive computed tomographic angiograms of the neck were reviewed,
      assessing the vascular supply of the anterior skin of the neck. Based on these
      findings, eight consecutive patients underwent head and neck reconstruction using
      a flap based on the dominant perforator of the region. In all cases, a perforator
      larger than 0.5 mm was identified within a 2-cm radius of the midpoint of the
      sternocleidomastoid muscle at its anterior border. This perforator was seen to
      emerge through the investing layer of deep cervical fascia as a fasciocutaneous
      perforator and to perforate the platysma on its ipsilateral side of the neck,
      proximal to the midline. This was seen to be a superior thyroid artery perforator
      in 89 of 90 sides and an inferior thyroid artery perforator in one case. Eight
      consecutive patients underwent preoperative imaging and successful flap planning
      and execution based on this dominant perforator. The superior thyroid artery
      perforator (STAP) flap demonstrates reliable vascular anatomy and is well suited
      to reconstruction of a broad range of head and neck defects. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373972
TI  - Patient-related keloid scar assessment and outcome measures.
AB  - BACKGROUND: Keloid scars cause pain, itching, functional limitation, and
      disfigurement, leading to psychological distress. Progress in treatment regimens
      is hindered by the lack of a universally accepted outcome measure. The Patient
      and Observer Scar Assessment Scale is a tool for the assessment of scars,
      incorporating an assessment by both clinician and patient. This study evaluates
      its application to keloids and compares it to the widely used Vancouver Scar
      Scale, which is considered the standard mode of assessment for scars. METHODS:
      Three observers using the two scales assessed 34 patients with 41 keloid scars
      independently. Patients evaluated their own scars simultaneously using the
      patient component of the Patient and Observer Scar Assessment Scale. Internal
      consistency, interobserver reliability, and convergent validity were examined.
      RESULTS: Both components of the Patient and Observer Scar Assessment Scale had
      high internal consistency (0.82 and 0.86 for patient and observer components,
      respectively); those rates were higher than the rate for the Vancouver Scar Scale
      (0.65). Interobserver reliability was "substantial" for the Vancouver Scar Scale
      (0.65) and "almost perfect" for the observer component of the Patient and
      Observer Scar Assessment Scale (0.85). Convergent validity was very strong (0.83,
      p < 0.01), although the patient component did not correlate well with either of
      the observer scales. Patients rated their scars worse than the observer average
      for 83 percent of the scars, and were influenced by color, stiffness, thickness,
      and irregularity (p < 0.05). CONCLUSION: The findings support the use of the
      Patient and Observer Scar Assessment Scale as a reliable and valid method of
      assessing keloid scars in a clinical context. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Diagnostic, II.

PMID- 22373973
TI  - The effect of neoadjuvant versus adjuvant irradiation on microvascular free flap
      reconstruction in sarcoma patients.
AB  - BACKGROUND: Sarcoma patients often require radiation therapy in addition to
      surgical resection. Although neoadjuvant irradiation possesses advantages over
      adjuvant irradiation related to smaller doses and field sizes, existing studies
      suggest adverse effects on wound healing and possibly microvascular free flap
      success. Conversely, microvascular reconstruction may counteract some of the
      negative effects of irradiation by replacing irradiated tissue with well
      vascularized unirradiated tissue from a distant site. METHODS: A review of
      sarcoma patients who underwent resection, microsurgical reconstruction, and
      either neoadjuvant or adjuvant irradiation was performed. RESULTS: A total of 119
      patients met inclusion criteria, of which 73 underwent neoadjuvant irradiation
      and 46 underwent adjuvant irradiation. Sarcomas were located in the head and neck
      (n = 47), trunk (n = 7), upper extremity (n = 15), and lower extremity (n = 50).
      The rate of perioperative (<= 30 days) complications was 26.9 percent, whereas
      the rate of late recipient-site complications was 14.3 percent. No significant
      differences in perioperative recipient-site (p = 0.19), donor-site (p = 1.00), or
      medical complications (p = 0.30) were observed between patients undergoing
      neoadjuvant and adjuvant irradiation. Free flap loss rates were lower in patients
      undergoing neoadjuvant irradiation (0 percent versus 8.7 percent, respectively; p
      = 0.02). Late recipient-site complications occurred less often in patients
      undergoing neoadjuvant radiation (6.8 percent versus 26.1 percent, respectively;
      p = 0.006). CONCLUSIONS: Neoadjuvant irradiation does not increase the risk of
      acute wound or microvascular complications when combined with free flap
      reconstruction, and is associated with fewer late recipient-site complications
      than adjuvant irradiation. These factors should be considered when determining
      the timing of radiation therapy in sarcoma patients undergoing oncologic
      resections and microsurgical reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 22373974
TI  - Prospective multicenter trial of modified retrograde percutaneous intramedullary
      Kirschner wire fixation for displaced metacarpal neck and shaft fractures.
AB  - BACKGROUND: The purpose of this prospective multicenter study was to assess the
      clinical and radiographic outcome of a newly devised technique of retrograde
      intramedullary fixation with multiple Kirschner wires in metacarpal neck and
      shaft fractures. METHODS: Between May of 2002 and June of 2007, a total of 121
      metacarpal fractures in 105 patients that were treated with the authors' modified
      intramedullary Kirschner wire fixation technique were included in this study. The
      average follow-up period was 10 months. The surgical outcome was assessed by
      clinical and radiographic data. RESULTS: The average range of motion in the
      metacarpophalangeal joint of the injured side was not significantly different
      from that of the uninjured side. There was no case of residual rotational
      deformity postoperatively, and the average Disabilities of the Arm, Shoulder and
      Hand questionnaire score was 8.5 (range, 0 to 41). Average dorsal apex angulation
      and average shortening were reduced significantly from 39.0 degrees and 3.1 mm,
      to 9.7 degrees and 0.0 mm, respectively, in neck fractures; and from 29.5 degrees
      and 3.0 mm, to 7.0 degrees and -0.1 mm in shaft fractures, respectively. Average
      time to union was 5.6 weeks, and there were no cases of nonunion. CONCLUSION:
      Modified retrograde intramedullary fixation with multiple Kirschner wires is a
      straightforward and reliable technique that successfully resulted in good
      functional and cosmetic results in addition to excellent bone healing. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373975
TI  - Discussion: Prospective multicenter trial of modified retrograde percutaneous
      intramedullary Kirschner wire fixation for displaced metacarpal neck and shaft
      fractures.

PMID- 22373976
TI  - The Oberlin procedure for restoration of elbow flexion with the da Vinci robot:
      four cases.
AB  - Robotics allows up to 40* visual magnification and 10* magnification of the
      surgeon's movements, and eliminates physiologic tremors. These properties should
      allow the development of mini-invasive limb surgery, especially of the brachial
      plexus. The purpose of this work was to test the feasibility of the restoration
      of elbow flexion according to the technique of Oberlin using a da Vinci robot.
      The authors' series included four patients (average age, 31 years) presenting
      with elbow flexion paralysis. They were operated on 8 months after injury using a
      da Vinci S robot. In three patients, the open technique (technique 1) was used,
      and the mini-invasive approach (technique 2) was used for the last one. Strength
      of elbow flexion was measured. After 1-year follow-up, all of the patients had
      recovered elbow flexion. No sensory or motor deficit was found in the ulnar nerve
      territory. There was no difficulty with technique 1; technique 2, however,
      required a conversion to technique 1 because of difficulty visualizing the
      operative field. The results of the authors' series show the feasibility of the
      robot-assisted technique for the Oberlin procedure. The lack of sensory feedback
      was not an issue. The development of specific retractors and instruments should
      improve the mini-invasive technique. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, V.

PMID- 22373977
TI  - Discussion: Hypertelorism correction: what happens with growth? Evaluation of a
      series of 95 surgical cases.

PMID- 22373979
TI  - Long-term effect of primary cleft rhinoplasty on secondary cleft rhinoplasty in
      patients with unilateral cleft lip-cleft palate.
AB  - BACKGROUND: The senior author routinely performs primary nasal reconstruction
      with every cleft lip repair. This addresses the nasal tip asymmetry and
      simplifies the definitive secondary rhinoplasty in adolescence. METHODS: A
      retrospective chart review was completed of all unilateral cleft secondary
      rhinoplasties performed by the senior author. The indications for secondary
      rhinoplasty were examined, anatomical features of the nose at the time of
      operation were documented, and the reconstructive techniques used were recorded.
      RESULTS: From 2001 to 2009, the senior author performed 116 secondary
      rhinoplasties in patients with a previously repaired unilateral cleft lip. The
      senior author performed 44 of the initial cleft lip repairs (group A). A Dibbell
      rhinoplasty was required in 26 percent, a Potter rhinoplasty was required in 5
      percent, a Tajima inverted-U incision was required in 70 percent, and an alar
      base resection was required in 53 percent. For those patients who did not undergo
      cleft lip repair with primary rhinoplasty by the senior author, 60 percent
      required a Dibbell rhinoplasty, Potter rhinoplasty was not used, 76 percent
      required a Tajima inverted-U incision, and 64 percent required an alar base
      resection. Group A had significantly greater dome symmetry when comparing the
      cleft side to the noncleft side (p = 0.001). Nostril apex height was also more
      symmetrical in group A (p = 0.105). CONCLUSION: Primary nasal reconstruction
      performed with cleft lip repair as described by the senior author makes the nasal
      tip more symmetric and requires less complex intervention at the time of
      definitive secondary rhinoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 22373978
TI  - Parameters of care for craniosynostosis:  craniofacial and neurologic surgery
      perspectives.
AB  - BACKGROUND: A multidisciplinary meeting was held from March 4 through 6, 2010, in
      Atlanta, Georgia, to conceptualize, map out, and operationalize the variables
      most relevant to the care of patients with craniosynostosis. In this article, the
      authors highlight the development of the craniofacial and neurologic surgery
      parameters of care. METHODS: Fifty-two conference attendees, representing a broad
      range of expertise in craniosynostosis care and 16 professional societies,
      participated in this working group. Literature and expert opinion were used to
      identify the variables important for the care of patients with craniosynostosis.
      In an iterative manner, specialty-specific data were compiled into draft
      recommendations and presented to all conference attendees. Cross-discipline
      analysis was used to assess the completeness of the data, facilitate exchange of
      ideas, and achieve consensus. RESULTS: Consensus was reached among the 52
      conference attendees and two post hoc reviewers in 18 areas of craniosynostosis
      care. Longitudinal parameters of care were developed for the diagnosis,
      treatment, and management of craniosynostosis in each of the specialty areas of
      care, from prenatal evaluation to completion of care in adulthood. CONCLUSIONS:
      To our knowledge, this is the first multidisciplinary effort to develop
      parameters of care and best practices for craniosynostosis. In conjunction with
      patient input, these parameters may help to heuristically develop core outcome
      sets that are important not only to patients and their families, but also to
      health care providers and health services and outcome researchers. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 22373980
TI  - Single-stage repair of asymmetrical bilateral cleft lip with contralateral lesser
      form defects.
AB  - BACKGROUND: Complete or incomplete cleft lip may include a contralateral lesser
      form of incomplete cleft lip to give rise to an asymmetrical bilateral cleft lip
      deformity. The principle of simultaneous bilateral cleft repair remains an area
      of contention with regard to asymmetrical cases, including a lesser form
      deformity. METHODS: The cleft lip database of the senior author (D.M.F.) was
      searched for patients with complete or incomplete bilateral cleft lip with a
      contralateral lesser form defect. Results were assessed by reviewing photographs
      and recording revisions. RESULTS: Of 111 patients with bilateral cleft lip, 35
      (32 percent) had asymmetrical cleft lip, with 13 patients having contralateral
      lesser form defects. All infants with complete cleft lip-cleft palate underwent
      presurgical orthodontics. All patients subsequently went on to single-stage
      bilateral cleft lip repair. Seven revisions were performed in the symmetrical
      complete bilateral cleft lip group; no revisions were performed in the
      asymmetrical bilateral cleft lip group. CONCLUSIONS: The authors recommend a
      single-stage operation for repair of the bilateral cleft lip irrespective of the
      extent: complete, incomplete, lesser form, symmetrical, or asymmetrical. This
      approach provides the best opportunity to achieve symmetry of the Cupid's bow and
      of the resultant scar, and provides the ideal opportunity for reconstruction of
      the prolabial deficiencies of the cutaneous roll, vermilion, and median tubercle.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373981
TI  - Split gluteal muscle flap for autoprosthesis buttock augmentation.
AB  - BACKGROUND: Several flaps have been described to provide autologous augmentation
      to the gluteal area. Since the authors' original description of a dermal fat flap
      for buttock augmentation during lower body lift in 2005, the procedure has been
      refined considerably. Unique to previously described flaps, the technique results
      in maximum projection of the buttock at its midportion. A decrease in fatty
      necrosis and greater mobility has been achieved by transitioning to a split
      gluteal musculocutaneous flap. METHODS: In a retrospective review from January of
      2004 to August of 2010, 200 patients, aged 24 to 57 years, underwent autologous
      buttock augmentation. The last 50 patients of the series underwent an
      incorporation of a split section of gluteus maximus muscle. Patients were
      followed for 6 months to 4 years. RESULTS: Of the 200 patients, 30 had the
      buttock flap as an isolated buttock lift and augmentation; the remainder of the
      procedures were performed in conjunction with a circumferential body lift.
      Incorporation of the split gluteus maximus muscle facilitated the rotation of the
      flap caudally and increased the vascular supply to the flap. Ten percent of the
      patients had minor complications, which included small areas of delayed wound
      healing and partial fat necrosis of the dermal flaps. In the group with split
      musculocutaneous flaps, there was no fatty necrosis. Results were maintained over
      time. CONCLUSIONS: This is a reliable, versatile, and efficient flap for
      autologous buttock augmentation. With recent modifications, the incidence of
      fatty necrosis has been substantially decreased. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 22373982
TI  - Connect with plastic surgery:  social media for good.

PMID- 22373988
TI  - Incidence of breast hematoma after placement of breast prostheses.
AB  - BACKGROUND: Prosthetic breast implants are frequently used by plastic surgeons
      for reconstructive and aesthetic procedures. One known complication of the
      procedure is postoperative breast hematoma. However, the incidence and risk
      factors of this problem are not fully characterized. METHODS: A retrospective
      analysis was performed of a prospectively collected patient medical record
      database based on procedure codes to identify breast hematomas and possible risk
      factors over a 12-year period from November of 1996 to October of 2008. RESULTS:
      One thousand nine hundred thirty-six operations were performed on 3474 breasts
      with prosthetic implants used. Average patient follow-up was 48.9 months, with 32
      hematomas identified following 32 operations. The latest hematoma identified was
      21 months after the procedure. Hematomas were identified on average 37 days after
      the operation. CONCLUSIONS: In the authors' experience, postoperative breast
      hematomas after prosthetic implant placement occur in 0.92 percent of breast
      prostheses placed. No individual surgical approach is associated with the
      occurrence of breast hematomas. Hematomas are not statistically associated with
      any measured patient or surgically defined characteristic. Specifically, no
      statistical significance was shown for larger implant size, reoperation,
      operative indication, type of surgery, or implant type as an independent risk
      factor. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 22373989
TI  - A review of 32 free flaps in patients with collagen vascular disorders.
AB  - BACKGROUND: Collagen vascular diseases affect multiple organs by the deposition
      of immunoglobulins along vascular basement membranes. This pathophysiology
      potentially makes these patients poor free flap candidates, with a possible
      increased risk of failure. The often concomitant finding of hypercoagulability
      may also compound the risk. METHODS: A retrospective review was conducted of all
      free flap reconstructions performed between 2005 and 2009. Of a total of 1251
      flaps, 25 patients, who underwent 32 flaps, were identified with connective
      tissue disorders. These included Sjogren syndrome, Raynaud phenomenon, rheumatoid
      arthritis, systemic lupus erythematosus, sarcoidosis, scleroderma, and
      multicentric thrombocytosis. RESULTS: The mean age of the patients was 51 years,
      and the average body mass index was 28.1 kg/m(2). Seven patients were on chronic
      immunosuppression. Flap reconstructions included seven deep inferior epigastric
      perforator flaps, 21 transverse rectus abdominis musculocutaneous flaps, one
      gluteal flap for breast reconstruction, and one anterolateral thigh and two
      radial forearm flaps for head and neck reconstruction. All flaps were performed
      with a single arterial and venous anastomosis. None had microvascular flap
      complications. There was one case of postoperative deep vein thrombosis. There
      were three cases of wound dehiscence and one case of ventral hernia. CONCLUSIONS:
      Blood vessels and soft tissues are injured by inflammation as the primary target
      of collagen vascular diseases. The increased incidence for thrombotic events
      deems them potentially high-risk free tissue transfer patients. The authors
      demonstrate from their series, however, that there is no increased risk of
      thrombosis, and this patient population should not be precluded from free flap
      reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID- 22373990
TI  - The importance of a skin bridge in peripheral tissue perfusion in perforator
      flaps.
AB  - BACKGROUND: Perforator flaps are increasingly used in reconstructive surgery.
      However, the microvascular perfusion pattern within these flaps remains
      essentially unknown. In perforator flaps, the importance of preserving the skin
      bridge at the base is still an object of debate. The authors hypothesized that
      dividing the skin bridge will increase peripheral tissue perfusion in islanded
      perforator flaps. METHODS: The abdominal panniculus in patients submitted to
      elective abdominoplasty was used (n = 24). Flap perfusion was measured by dynamic
      laser-induced fluorescence videoangiography. The fluorescent dye indocyanine
      green was injected intravenously before and after conversion of a perforator flap
      with an intact skin bridge into an islanded perforator flap. To evaluate
      perfusion, mean pixel intensity and mean perfusion index were calculated in a
      control zone and in two zones in the flap. RESULTS: In zone I (the most
      peripheral zone), surgical release of the skin bridge increased mean pixel
      intensity (19.1 +/- 1.9 versus 24.1 +/- 2.1; p < 0.001). The mean perfusion index
      was calculated as 7.5 +/- 5.5 and 12.6 +/- 6.3 before and after surgical
      conversion to islanded perforator flaps, respectively. In zone II (the more
      proximal zone), mean pixel intensity increased (from 30.8 +/- 2.8 to 33.7 +/-
      2.3; p < 0.001) after surgical release of the skin bridge. The mean perfusion
      index was 18.5 +/- 11.1 and 15.6 +/- 6.2. CONCLUSIONS: In this human experimental
      study, conversion of a perforator flap with a skin bridge into an islanded
      perforator flap increases peripheral tissue perfusion. This finding provides a
      physiologic basis for using islanded perforator flaps, with enhanced flap
      mobility and length.

PMID- 22373991
TI  - Early growth response factor-1:  expression in a rabbit flexor tendon scar model.
AB  - BACKGROUND: Adhesion formation limits functional recovery after flexor tendon
      repair. Various growth factors have been implicated in the adhesion scar process.
      Early growth response factor-1 (EGR-1), a transcription factor associated with
      synthesis of a variety of key fibrotic growth factors and expression of
      extracellular matrix genes, has never been identified in a tendon repair model.
      METHODS: Thirty New Zealand White rabbit forepaws underwent laceration and repair
      of the middle digit flexor digitorum profundus equivalent in zone II. Sodium
      morrhuate, a topical sclerosing agent, or phosphate-buffered saline, a standard
      control, was applied to the repair during closure of the tendon sheath. Tendons
      were harvested from operated and unoperated forepaws at increasing time intervals
      (1, 3, 7, 14, and 28 days). Tissues were analyzed by immunohistochemistry and
      Masson trichrome staining. RESULTS: Immunohistochemistry demonstrated that EGR-1
      is expressed at the site of tendon repair, along the epitenon of the tendon, and
      in the infiltrate of inflammatory cells in the surrounding sheath-scar matrix.
      Control, unoperated tendons demonstrated baseline EGR-1 expression within
      epitenon cells. EGR-1 was maximally expressed on postoperative day 7. Sodium
      morrhuate and phosphate-buffered saline demonstrated no difference in their
      ability to augment tendon adhesion scar formation. CONCLUSIONS: : Findings
      demonstrate the following: (1) EGR-1 expression is increased in the tendon wound
      environment after flexor tendon laceration repair; (2) normal epitenon cells have
      low, baseline levels of EGR-1 expression; and (3) sodium morrhuate does not
      augment scar matrix production more than phosphate-buffered saline. The ideal
      tendon scar model was not generated.

PMID- 22373992
TI  - Epidermal regeneration by micrograft transplantation with immediate 100-fold
      expansion.
AB  - BACKGROUND: Major loss of skin following burns or trauma requires skin grafting
      for repair. In addition, chronic wounds frequently require skin grafts. Current
      treatments are either cumbersome, limited in possible expansion ratio, costly, or
      require extensive time for treatment. This study investigates a new way of
      regenerating skin after major burns and other trauma, providing 100-fold
      expansion of a split-thickness skin graft. METHODS: Submillimeter micrografts
      were created by controlled mincing of a split-thickness skin graft and
      transplanted to porcine full-thickness wounds. By creating an incubator-like
      microenvironment using wound chambers, the micrografts provide
      reepithelialization whether placed dermal side up or dermal side down. RESULTS:
      Transplantation of micrografts in a 1:100 expansion ratio results in complete
      epithelialization of both healthy and diabetic wounds within 14 days. In
      comparison, nontransplanted wounds showed 62 percent reepithelialization in
      healthy pigs and 49 percent in diabetic pigs at the corresponding time point.
      CONCLUSIONS: Minced skin micrografts are very effective in wound repair and can
      provide 100-fold expansion of a skin graft. Early clinical results confirm the
      utility of this technique.

PMID- 22373993
TI  - Correction of severe ptosis with a silicone implant suspensor:  22 years of
      experience.
AB  - BACKGROUND: Patients with severe ptosis caused by poor or absent function of the
      levator muscle but with good frontalis muscle excursion usually benefit from a
      frontalis sling procedure. This is currently carried out using organic or
      inorganic material to connect the upper eyelid to the frontalis muscle. METHODS:
      The aim of this study was to evaluate retrospectively 112 patients who underwent
      frontalis sling procedures between 1989 and 2011 using a preformed silicone
      implant suspensor to correct severe ptosis. RESULTS: The results obtained using
      this technique were good or fair in 95.54 percent of the cases and poor in 4.46
      percent of the cases. The authors discuss the results of the study and the cases
      in which the procedure should be indicated and highlight the advantages of the
      method. CONCLUSION: The availability of this low-cost sterile device, together
      with the fact that it is ready to use, requires less invasive surgery, saves
      time, and is sufficiently versatile to allow adjustments to be made at any time,
      makes the silicone eyelid sling an attractive choice for correcting ptosis.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373994
TI  - Donor facial composite allograft recovery operation: Cleveland and Boston
      experiences.
AB  - BACKGROUND: Complexity of logistic issues related to facial transplantation
      includes donor tissue recovery, recipient preparation, and operative execution.
      Limited information is available on the intricate process associated with facial
      allograft procurement in the United States. METHODS: The face transplant teams at
      the Cleveland Clinic and Brigham and Women's Hospital have combined their
      experiences regarding collaboration with organ procurement organizations and
      institutional review boards, and outlined technical and logistic challenges
      encountered during the process of facial allograft procurement and compared them
      with those of solid organ procurement. RESULTS: In a collaborative effort, both
      programs have created comprehensive guidelines for all aspects involved in donor
      facial allograft procurement. CONCLUSIONS: The authors suggest that every face
      transplant team should develop a thorough understanding of the local and regional
      legislative issues related to organ and tissue donation and ethical concerns
      surrounding this procedure. The recovery plan has to be communicated extensively
      among all members of the team. The Cleveland and Boston teams hope their
      experiences may help other teams in the process of building new face transplant
      programs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 22373995
TI  - Arteries of the thumb:  description of anatomical variations and review of the
      literature.
AB  - BACKGROUND: Vascular studies of the thumb have reported conflicting results; even
      the anatomical nomenclature differs between studies. The main purpose of this
      study was to describe the local patterns of thumb vascular anatomy. METHODS: The
      authors studied 30 fresh right hands from male and female cadavers using a
      vascular injection technique with methyl methacrylate. The origins, course, and
      characteristics of the arteries of the thumb are described. RESULTS: The princeps
      pollicis artery was present in all of the hands and was the origin of the radial
      and ulnar digital arteries in 73.3 percent. The radial and ulnar digital arteries
      originated from the princeps pollicis artery or branches of the palmar metacarpal
      artery in 53.3 and 83.3 percent of the dissections, respectively. Dorsally, the
      dorsal ulnar artery was present in 100 percent of the hands and originated mainly
      from the princeps pollicis artery (73.3 percent). The dorsal radial artery was
      present in 66.7 percent of dissections as a direct branch of the radial artery.
      Several anastomoses were observed between the radial and ulnar digital arteries
      and between the dorsal and palmar systems. CONCLUSIONS: Various arterial systems
      were described in the arterial irrigations of the thumb, such as the dorsopalmar
      and radioulnar. The complex configuration and the multiple anastomotic arcades
      between the arterial systems allow the thumb to survive even after severe lesions
      of nearly all of the arteries. The presence of these interconnected systems
      provides multiple alternatives in flap design without endangering their survival.

PMID- 22373996
TI  - Top five craniofacial techniques for training in plastic surgery residency.
AB  - BACKGROUND: Despite increasing specialization of craniofacial surgery, certain
      craniofacial techniques are widely applicable. The authors identified five such
      craniofacial techniques and queried American Society of Plastic Surgeons members
      and plastic surgery program directors regarding their comfort level with the
      procedures and their opinion on resident training for these selected procedures.
      METHODS: First, a select group of senior craniofacial surgeons discussed and
      agreed on the top five procedures. Second, active American Society of Plastic
      Surgeons were surveyed regarding their opinion on training and their comfort
      level with each procedure. Third, plastic surgery residency program directors
      were studied to see which of the top five procedures are taught as part of the
      plastic surgery residency curriculum. RESULTS: The top five widely applicable
      craniofacial procedures are technically described and include the following: (1)
      cranial or iliac bone graft for nasal reconstruction, (2) perialar rim bone
      graft, (3) lateral canthopexy, (4) osseous genioplasty, and (5) bone graft
      harvest for orbital floor defects. For practicing plastic surgeons, comfort level
      in all procedures increased with advancing years in practice (except those with
      <5 years). A majority of plastic surgeons (>75 percent), especially those with
      craniofacial fellowship training, felt competent in all procedures except osseous
      genioplasty (53 percent). Plastic surgery program directors agreed that all top
      five procedures should be mastered by graduation. CONCLUSIONS: Although program
      directors felt that all five selected craniofacial procedures should be taught
      and mastered during residency training, plastic surgeons without craniofacial
      fellowship training were less comfortable with the techniques. Residency training
      goals should include competence in core craniofacial techniques.

PMID- 22373998
TI  - Discussion: Frontofacial monobloc distraction in the very young: a review of 12
      consecutive cases.

PMID- 22373997
TI  - Frontofacial monobloc distraction in the very young:  a review of 12 consecutive
      cases.
AB  - BACKGROUND: Frontofacial monobloc advancement by distraction osteogenesis is now
      accepted as an effective treatment for children with syndromic and other complex
      forms of craniosynostosis because it combines cosmetic advantages with the
      ability to treat such complications as raised intracranial pressure, advancing
      exorbitism, and upper airway obstruction in one procedure. In the severely
      affected child, these complications may be present at an early age, but because
      of the scale of monobloc surgery, surgeons have been reluctant to perform it on
      very young children. METHODS: The authors report a series of 12 children younger
      than 30 months with various craniosynostosis-associated syndromes complicated by
      multiple functional problems--including raised intracranial pressure, exposure of
      the eyes, airway obstruction, and feeding problems--who underwent frontofacial
      monobloc surgery by distraction osteogenesis. RESULTS: The mean age at operation
      was 18 months. Mean advancement achieved was 16.6 mm for the upper face and 17 mm
      for the midface. Ocular protection and reduction of intracranial pressure (when
      raised) were achieved in all children. Airway improvement was achieved in all but
      one child. Although not the primary indication for surgery, there was also a
      marked improvement in every patient's appearance. Complications included two
      cerebrospinal fluid leaks, pin-site infections, frame slippage requiring
      replacement, and enophthalmos in one patient. CONCLUSION: The frontofacial
      monobloc advance incorporating distraction osteogenesis can be undertaken with
      acceptable morbidity even in the very young child and good functional outcomes
      achieved with one operation where previously more were required. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22373999
TI  - Impact of 22q deletion syndrome on speech outcomes following primary surgery for
      submucous cleft palate.
AB  - BACKGROUND: Patients with 22q deletion syndrome are at increased risk of
      submucous cleft palate and velopharyngeal insufficiency. The authors' aim is to
      evaluate speech outcomes following primary Furlow palatoplasty or pharyngeal flap
      for correction of velopharyngeal insufficiency in submucous cleft palate patients
      with and without 22q deletion syndrome. METHODS: Records of submucous cleft
      palate patients who underwent primary surgery between 2001 and 2010 were
      reviewed. Data included 22q deletion syndrome diagnosis, age at surgery,
      procedure, preoperative nasopharyngoscopy and nasometry, speech outcomes,
      complications, and secondary surgery rates. RESULTS: Seventy-eight submucous
      cleft palate patients were identified. Twenty-three patients had 22q deletion
      syndrome. Fewer 22q deletion syndrome patients obtained normal resonance on
      perceptual assessment compared with nonsyndromic patients (74 percent versus 88
      percent). A similar difference existed based on postoperative nasometric scores.
      Among 22q deletion syndrome patients, similar success rates were achieved with
      Furlow palatoplasty and pharyngeal flap. No difference in the proportion improved
      postoperatively was noted between 22q deletion syndrome and nonsyndromic groups.
      One complication was experienced per group. More revision operations were
      indicated in the 22q deletion syndrome group (17 percent) compared with the
      nonsyndromic group (4 percent). Median times to normal resonance for 22q deletion
      syndrome and nonsyndromic patients were 150 weeks and 34 weeks, respectively.
      Adjusting for multiple variables, 22q deletion syndrome patients were 3.6 times
      less likely to develop normal resonance. CONCLUSION: Careful selection of Furlow
      palatoplasty or pharyngeal flap for primary repair of submucous cleft palate is
      highly effective in 22q deletion syndrome patients and yields results approaching
      those of nonsyndromic patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 22374000
TI  - Updating the epidemiology of cleft lip with or without cleft palate.
AB  - BACKGROUND: Much of the literature on the epidemiology of cleft lip with or
      without cleft palate is more than three decades old. The question arose as to
      whether there has been any recent change or trend in its rate of occurrence.
      METHODS: The number of live births with cleft lip or other congenital anomalies
      was solicited from national and international organizations. Data were collected
      for 34 states and 30 countries for the years 2002 to 2006. All data were
      normalized and reported per 10,000 live births. Descriptive statistics, in
      addition to correlation and regression, were used to analyze the data. RESULTS:
      Data for the 5-year period demonstrated that the overall congenital anomaly rate
      increased in the United States and decreased internationally. The states with the
      highest and lowest rates were Maryland (21.46) and West Virginia (2.59),
      respectively. The United States cleft lip national rate averaged 7.75. Countries
      with the highest and lowest rates were Japan (19.05) and South Africa (3.13),
      respectively. Internationally, the rate of cleft lip declined, with an average
      overall prevalence of 7.94. CONCLUSIONS: The average prevalence of cleft lip with
      or without cleft palate was 7.75 per 10,000 live births in the United States and
      7.94 per 10,000 live births internationally. The trends diverged over the 5-year
      period, as the rate was stable in the United States and the international rate
      declined.

PMID- 22374001
TI  - Indian American rhinoplasty: an emerging ethnic group.
AB  - BACKGROUND: The goal of this article is to help U.S. plastic surgeons better
      understand why Indian American rhinoplasty is different from other ethnic
      rhinoplasties in their practice. The study is composed of three parts: a review
      of the cultural perspectives of Indian Americans toward aesthetic surgery, an
      investigation into the aesthetic ideals of the Indian American nose, and an
      overview of operative strategies to achieve these ideals. METHODS: A total of 35
      Indian Americans who were dissatisfied with their nasal appearance were analyzed,
      15 prospectively and 20 retrospectively. Group 1 consists of 15 Indian American
      women who were unhappy with the appearance of their nose. Standard photographs
      and anthropometric measurements were taken. Anterior and lateral photographic
      views were morphed to the patient's subjective ideal. Actual and ideal images
      were compared and analyzed. Group 2 consists of a retrospective review of 20
      consecutive Indian American rhinoplasty cases with a follow-up of 1 to 6 years.
      RESULTS: The majority of the group 1 participants complained of a dorsal "hump,"
      a downwardly rotated tip, and/or a large nose. The average subjective ideal
      nasolabial angle was determined to be 101.6 degrees. Based on the authors'
      analysis, three categories of nasal deformities were identified and operative
      strategies are discussed. Evaluation of the 20 clinical cases indicated that a
      more conservative surgical approach is warranted in these patients. CONCLUSIONS:
      Indian American rhinoplasty patients present a challenging range of nasal
      deformities requiring careful surgical planning. A clear understanding of the
      patient's desires is essential to achieving patient satisfaction. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22374002
TI  - Experiential learning in aesthetic surgery training: a quantitative comparison
      among surgical subspecialties.
AB  - BACKGROUND: The specialty of plastic surgery has evolved to encompass a wide
      breadth of both reconstructive and aesthetic surgery. Practitioners in other
      specialties have increasingly advanced on procedures and areas that have
      traditionally been served by plastic surgeons. To date, no evaluation and
      comparison of the operative experience of graduating residents from various
      specialties has been performed. METHODS: The authors review the case log
      statistical reports of the Accreditation Council for Graduate Medical Education.
      For each specialty, this annual report highlights the average number of cases
      performed for all graduating residents. The national case log reports were
      reviewed for dermatology, ophthalmology, otolaryngology, and plastic surgery.
      Four procedures (i.e., blepharoplasty, face lift, liposuction, and rhinoplasty)
      were compared for residents graduating in the 2006 to 2010 academic years. The
      hypothesis that no difference exists between the average numbers of aesthetic
      procedures performed by various specialty residency training was tested using a
      two-sample t statistic. RESULTS: For blepharoplasty, face lift, and liposuction,
      the higher number of cases performed by graduating plastic surgery residents was
      statistically significant (p < 0.00001) for all years examined. Although plastic
      surgery trainees graduating from 2006 to 2010 had a higher number of recorded
      rhinoplasties, this difference in case logs was statistically significant only
      for plastic surgery residents graduating in 2008. CONCLUSIONS: The quantitative
      operative experience of graduating plastic surgery residents for selected
      aesthetic surgery cases exceeds that of other surgical subspecialties. Given the
      exposure and strength of plastic surgery training, plastic surgeons should remain
      at the forefront of aesthetic surgery.

PMID- 22374003
TI  - Orthognathic surgery in cleft patients.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify the skeletal changes in the cleft patient that necessitate
      surgery. 2. Describe the orthodontic principles that precede surgical treatment.
      3. Demonstrate the surgical principles involved in cleft orthognathic surgery and
      how to avoid common pitfalls particular to cleft orthognathic surgery. 4.
      Anticipate when dentoalveolar distraction can help in the treatment of problems
      not easily treated with conventional orthognathic techniques. SUMMARY: This CME
      article covers the basic multidisciplinary approach to the treatment of patients
      requiring a combined orthodontic orthognathic approach to their skeletally based
      malocclusion. The dentoskeletal abnormalities are described for these patients,
      as are the fundamental orthodontic principles in the presurgical treatment of
      these patients. The basic surgical principles are discussed in general, and the
      reader is provided with advice on avoiding common pitfalls. Specific attention is
      given to the more recent advances in dentoalveolar distraction in cases of large
      defects that would have been difficult to treat using conventional orthognathic
      surgery. Videos are provided to illustrate the general principles in treating the
      cleft orthognathic patient and to illustrate the treatment of large defects using
      dentoalveolar distraction.

PMID- 22374004
TI  - Does previous head and neck irradiation increase vascular complications in free
      autologous reconstruction?

PMID- 22374006
TI  - Venous thromboembolism following microsurgical breast reconstruction: an
      objective analysis in 225 consecutive patients using low-molecular-weight heparin
      prophylaxis.

PMID- 22374008
TI  - Total muscular implant coverage in alloplastic breast reconstruction.

PMID- 22374010
TI  - Delayed cosmetic improvement following breast conservation therapy.

PMID- 22374012
TI  - Can we really say that no patients benefit from ligament reconstruction tendon
      interposition?

PMID- 22374014
TI  - Improving humanitarian medical mission efficacy.

PMID- 22374016
TI  - Haiti and the road to recovery:  surviving the human aftershocks, battles with
      the cholera epidemic, and the anticipation of a new political era.

PMID- 22374017
TI  - FaceTime with Apple and information technology.

PMID- 22374018
TI  - Craniomaxillofacial surgery in China: what lies ahead?

PMID- 22374019
TI  - A revised approach for mandibular reconstruction with the vascularized iliac
      crest flap by virtual surgical planning.

PMID- 22374020
TI  - A useful refinement of cartilage-sparing (Mustarde and Furnas) otoplasty.

PMID- 22374021
TI  - The retroangular flap in facial reconstruction:  the exhaustive point of view.

PMID- 22374022
TI  - Treatment of symptomatic facial nerve paralysis with lower eyelid fascia lata
      suspension.

PMID- 22374023
TI  - A new one-stage method for nose reconstruction:  the supratrochlear artery
      perforator propeller flap.

PMID- 22374024
TI  - Reconstruction of elbow flexion by end-to-side neurorrhaphy in phrenic nerve
      transfer.

PMID- 22374025
TI  - Cancer risk among cosmetic breast implant patients: an update of the Los Angeles
      study.

PMID- 22374026
TI  - First report of nodal marginal zone B-cell lymphoma associated with breast
      implants.

PMID- 22374027
TI  - Detection of bacterial biofilm in double capsule surrounding mammary implants: 
      findings in human and porcine breast augmentation.

PMID- 22374028
TI  - A novel technique for nipple-areola complex reconstruction:  the acellular dermal
      matrix onlay graft.

PMID- 22374029
TI  - Correction of lower pole insufficiency in implant-based breast reconstruction.

PMID- 22374030
TI  - Incidence of cosmetic surgery following free flap breast reconstruction: an
      opportunity to build a cosmetic practice through reconstruction?

PMID- 22374031
TI  - Extended latissimus dorsi rotational V-Y advancement flap for the reconstruction
      of axillary defects after excision of hidradenitis suppurativa.

PMID- 22374032
TI  - Sternal wound coverage using the supraclavicular artery island flap.

PMID- 22374033
TI  - Perforator-based monitoring skin islands in free muscle flaps:  teaching old dogs
      new tricks.

PMID- 22374034
TI  - Blood glucose measurement in flap monitoring for salvage of flaps from venous
      thrombosis.

PMID- 22374035
TI  - A superficial texture analysis of 70% glycolic acid topical therapy and striae
      distensae.

PMID- 22374036
TI  - Technical facilitation of the fleur-de-lis abdominoplasty for symmetrical
      resection patterns in massive weight loss patients.

PMID- 22374037
TI  - Lipofilling of perineal and vaginal scars:  a new method for improvement of pain
      after episiotomy and perineal laceration.

PMID- 22374038
TI  - Nearly circumferential pharyngoesophagectomy reconstruction with a double-skin
      paddle anteromedial thigh and sartorius muscle free flap.

PMID- 22374039
TI  - Surgical techniques to achieve direct anterolateral thigh flap donor-site
      closure.

PMID- 22374040
TI  - Endoscope-assisted perforator flap harvest.

PMID- 22374041
TI  - Prone induction of anesthesia using laryngeal mask airway in liposculpting
      surgery.

PMID- 22374042
TI  - Implementation of the World Health Organization surgical safety checklist in
      plastic and reconstructive patients.

PMID- 22374043
TI  - Vaporization of cutaneous neurofibromas with an erbium: yttrium-aluminum-garnet
      laser:  a comparative histologic evaluation.

PMID- 22374044
TI  - Stem cell studies in plastic surgery:  are plastic surgery journals really
      interested in stem cells?

PMID- 22374045
TI  - Employed plastic surgeons.

PMID- 22374046
TI  - Maximizing the economics of the marking pen.

PMID- 22374047
TI  - Nanoplasmonic sensing of metal-halide complex formation and the electric double
      layer capacitor.
AB  - Many nanotechnological devices are based on implementing electrochemistry with
      plasmonic nanostructures, but these systems are challenging to understand. We
      present a detailed study of the influence of electrochemical potentials on
      plasmon resonances, in the absence of surface coatings and redox active
      molecules, by synchronized voltammetry and spectroscopy. The experiments are
      performed on gold nanodisks and nanohole arrays in thin gold films, which are
      fabricated by improved methods. New insights are provided by high resolution
      spectroscopy and variable scan rates. Furthermore, we introduce new analytical
      models in order to understand the spectral changes quantitatively. In contrast to
      most previous literature, we find that the plasmonic signal is caused almost
      entirely by the formation of ionic complexes on the metal surface, most likely
      gold chloride in this study. The refractometric sensing effect from the ions in
      the electric double layer can be fully neglected, and the charging of the metal
      gives a surprisingly small effect for these systems. Our conclusions are
      consistent for both localized nanoparticle plasmons and propagating surface
      plasmons. We consider the results in this work especially important in the
      context of combined electrochemical and optical sensors.

PMID- 22374048
TI  - The anatomy lesson of Dr Nicolaes Tulp: what can it teach us today?
AB  - We report on the use of a high fidelity patient simulator (SimMan) within a
      clinical lab setting to teach learning disability nursing students about epilepsy
      management. We had previously prepped the students with verbal discussions on
      epilepsy management and, when the simulator began to undergo a seizure, small
      groups of students managed the unfolding scenario. We received written feedback
      from the students on the experience, and with reference to this and to the wider
      literature we consider the benefits of this approach to patient care. We surmise
      that lessons learned here will be applicable to trainee professionals from other
      parts of the register and in other fields allied to healthcare. We anticipate
      that this will improve care for people with intellectual disability in line with
      recommendations in Health Care for All (2008).

PMID- 22374049
TI  - Serum non-high-density lipoprotein cholesterol (non-HDL-C) levels and
      cardiovascular mortality in chronic hemodialysis patients.
AB  - BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) has been
      proposed as a predictor of cardiovascular disease (CVD) in the general
      population. The aim of this study was to evaluate the utility of non-HDL-C in
      predicting CV mortality in chronic hemodialysis (HD) patients. METHODS: We
      calculated the serum non-HDL-C level of 259 HD patients by subtracting their HDL
      C levels from their total cholesterol. Cox proportional hazards models were used
      to estimate the hazards ratio (HR) for CV mortality and the 95% confidence
      interval (CI). A receiver-operating characteristic (ROC) analysis was performed
      to estimate the relationship between sensitivity and specificity of a diagnostic
      parameter. RESULTS: There were 44 deaths (17.0%) during the follow-up period, 33
      (12.7%) of which were due to CVD. A multivariate Cox analysis with adjustments
      for age, diabetes, dialysis vintage, systolic blood pressure, serum albumin, and
      lipid levels showed that non-HDL-C was an independent predictor of CV mortality
      (HR 1.015, 95% CI 1.004-1.025, p = 0.0083). An ROC analysis showed that the plots
      of the non-HDL-C levels yielded significant specificity and sensitivity for
      predicting the risk of CVD mortality in HD patients [area under the curve (AUC)
      0.62416; p = 0.0366; cutoff value 111.0 mg/dl]. The Kaplan-Meier survival curves
      of HD patients showed significant differences in CV mortality according to their
      tertiles with respect to serum non-HDL-C levels (p = 0.0165). CONCLUSION: The
      results of this study suggest that serum non-HDL-C level is a significant CV
      mortality predictor of chronic HD patients.

PMID- 22374050
TI  - Characterisation of tri-ruthenium dihydride complexes through the computation of
      NMR parameters.
AB  - Density functional theory has been used to provide atomic-level detail on the
      structures of metal hydride intermediates that have previously been proposed in
      the hydrogenation of phenylacetylene using Ru(3)(CO)(10)(PPh(3))(2). Based on a
      comparison of energetic data along with computed chemical shifts and coupling
      constants, we suggest that the detected species share a Ru(3)(MU-H)(MU-H) motif,
      with two distinct bridging hydride sites, rather than the terminal hydride
      proposed previously. The work illustrates how theory can be used as a complement
      to spectroscopy to enhance the accuracy of deductions, and to provide a basis for
      future rational design of second generation catalysts.

PMID- 22374051
TI  - When to sheath the scalpel.

PMID- 22374052
TI  - A new perspective in support of mandating research during oral surgery residency
      training.

PMID- 22374054
TI  - Methodological limitations of a systematic review evaluating inferior or double
      joint spaces injection versus superior joint space injection for
      temporomandibular disorders.

PMID- 22374056
TI  - Head and neck oncology--teamwork.

PMID- 22374058
TI  - Re: He Y, Zhang ZY, Zhu HG, et al: Double-barrel fibula vascularized free flap
      with dental rehabilitation for mandibular reconstruction. J Oral Maxillofac Surg
      69:2663, 2011.

PMID- 22374059
TI  - Postoperative bleeding after dental extraction in liver pretransplant patients.
AB  - PURPOSE: The aim of this prospective observational study was to evaluate the
      incidence of postoperative bleeding after dental extraction in candidates for
      liver transplantation and the efficacy of the association of tranexamic acid and
      absorbable hemostatic sponges. PATIENTS AND METHODS: All individuals referred for
      oral health evaluation requiring extraction were considered in this study.
      Patients were included in the analysis when the blood examinations showed a
      platelet count of 30,000/mm(3) or greater and an international normalized ratio
      (INR) of 3.0 or less. In group 1 local pressure was applied by use of gauze
      soaked with tranexamic acid, and in group 2 gauze without tranexamic acid was
      used. Absorbable hemostatic sponges and cross sutures were used as a standard
      hemostatic measure. RESULTS: In the 23 patients included in this study, 84 simple
      extractions were performed during 35 dental surgical procedures. The main
      preoperative blood tests found the following: a mean hematocrit level of 34.54%
      (SD, 5.84%; range, 21.7%-44.4%), platelet counts from 31,000/mm(3) to
      160,000/mm(3), and a mean INR of 1.50 (SD, 0.39; range, 0.98-2.59). Postoperative
      bleeding occurred during only 1 procedure (2.9%), and local pressure with gauze
      was effective for achieving hemostasis. No statistically significant difference
      in the time to hemostasis was found between the 2 groups. CONCLUSIONS: This study
      found a low risk of bleeding for tooth extractions in patients with liver
      cirrhosis, INRs of 2.50 or less, and platelet counts of 30,000/mm(3) or greater.
      Blood transfusions were not needed, and in the case of postoperative bleeding,
      the use of local hemostatic measures was satisfactory.

PMID- 22374060
TI  - Novel endovascular treatment of enlarging facial artery pseudoaneurysm resulting
      from molar extraction: a case report.
AB  - PURPOSE: A novel endovascular therapy to treat a pseudoaneurysm as a complication
      of molar tooth extraction is described. PATIENTS AND METHODS: A 20-year-old man
      presented 2 weeks after third molar tooth extraction with an enlarging pulsatile
      jaw mass, identified as a facial artery pseudoaneurysm. Endovascular embolization
      with microcoils and a liquid embolic agent, Onyx, was performed. The use of Onyx
      in this manner is an off-label use. RESULTS: Immediately after treatment, the
      pulsatile mass resolved and remained obliterated at 2 months of follow-up.
      CONCLUSIONS: Onyx embolization of facial artery vascular lesions can be safely
      accomplished while avoiding microvascular complications and provides a
      satisfactory and durable result.

PMID- 22374061
TI  - Pott puffy tumor after maxillary tooth extraction.

PMID- 22374062
TI  - Adipose-derived mesenchymal stem cells enhance healing of mandibular defects in
      the ramus of swine.
AB  - PURPOSE: This study investigated the effect of adipose-derived mesenchymal stem
      cells (ASCs) injected locally or systemically on the bone regeneration of a 10-mm
      diameter cylindrical noncritical-size defect in the ramus of the pig mandible.
      MATERIALS AND METHODS: Fifteen Yorkshire pigs, weighing 60 to 80 kg, received
      bilateral 10-mm-diameter cylindrical surgical defects in each ramus of the
      mandible. Pigs received 1) a direct injection into the defect of 2.5 million
      carboxy-fluorescein diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig
      donors (n = 6); 2) an ear vein injection of 5 million carboxy-fluorescein
      diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig donors (n = 6); or 3)
      an ear vein injection of culture Dulbecco's Modified Eagle's Medium without stem
      cells (control; n = 3). Pigs from each treatment were sacrificed at 1 hour, 2
      weeks, or 4 weeks after surgery. Healing of the defect was evaluated by dual
      energy x-ray absorptiometry, micro-computed tomography, fluorescent microscopy,
      and histology. RESULTS: Bone healing was accelerated in the ASC-injected
      treatment groups at 2 and 4 weeks after surgery compared with the control pigs.
      CONCLUSIONS: Results from this animal model provide evidence that the injection
      of ASC locally into a bone defect or systemically can accelerate the healing of
      bone.

PMID- 22374063
TI  - Swelling of the anterior mandible.

PMID- 22374064
TI  - Dental impactions related to pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum is a rare genetic disorder causing degeneration and
      calcification of elastic fibers, leading to injuries in the skin, retina, and
      cardiovascular system. This report describes a case of a 30-year-old woman whose
      diagnosis of pseudoxanthoma elasticum was confirmed after a skin biopsy. The
      patient presented at the Clinical Management Unit of the Department of Oral and
      Maxillofacial Surgery, Virgen del Rocio Hospital (Seville, Spain) with pain
      related to a semi-erupted lower first molar. Radiologic examination disclosed
      multiple dental impactions. Cases of oligodontia, amelogenesis imperfecta, and
      mucosal lesions related to pseudoxanthoma elasticum were found in the current
      literature, but there were no reports of multiple dental impactions.

PMID- 22374065
TI  - New bone formation in nongrafted sinus lifting with space-maintaining management:
      a novel technique using a titanium bone fixation device.
AB  - PURPOSE: Sinus lifting without graft materials allows new bone formation in the
      sinus, but the amount of bone formation varies. This study aimed to investigate
      whether nongrafted sinus lifting using a titanium bone fixation device can
      promote bone formation in the sinus. MATERIALS AND METHODS: Patients with
      atrophic posterior maxillae jeopardizing implant stability were included. After
      nongrafted sinus lifting in combination with implant placement, repositioning of
      the bone window and additional space-maintaining management were performed by use
      of the bone fixation device. The primary variables recorded retrospectively
      included implant survival and preoperative and postoperative alveolar crest
      height with and without Schneiderian membrane perforation. Independent variables
      included patient demographics, position and dimension of the implants,
      complications, and follow-up period. The t test was used for comparing
      differences in bone levels. The implant survival rate was estimated by uses of
      Kaplan-Meier statistics. RESULTS: The study included 11 patients (4 men and 7
      women) and a total of 21 implants. Radiographically, new bone formation around
      the implant was generally observed in accordance with the implant apex.
      Postoperative alveolar crest height (mean, 10.9 +/- 2.2 mm) was significantly
      higher compared with residual alveolar crest height (mean, 4.7 +/- 1.4 mm), and
      no significant difference in bone formation was seen according to membrane
      perforation. The cumulative survival rate was 95.2%. CONCLUSIONS: This nongrafted
      sinus-lifting procedure using a bone fixation device could attain predictable
      bone formation. Additional space-maintaining management using a bone fixation
      device in a nongrafted sinus lift offers a useful technique for promoting bone
      formation in the sinus.

PMID- 22374066
TI  - Induced osteogenesis using a new periosteal distractor.
AB  - PURPOSE: We developed a new device mainly composed of a titanium mesh to distract
      the periosteum. The purpose of this study is to evaluate induced osteogenesis by
      periosteal distraction with the new device. MATERIALS AND METHODS: We divided 12
      Japanese male rabbits into 3 groups, with 4 rabbits in each. In all groups the
      calvarial periosteum was reflected, and 1 side of the titanium mesh was fixed to
      the bone surface with 2 micro-screws. In groups 1 and 2, an elevation screw was
      inserted into a serrated hole on the other side of the plate 7 days after
      surgery. Then the device was activated at a rate of 0.5 mm every 12 hours for 5
      days. At 4 weeks of the consolidation period, group 1 was killed, followed by
      group 2 at 6 weeks. Group 3 (control) received no screws, and hence no activation
      was performed. In group 3, 2 animals were killed 4 weeks after titanium mesh
      insertion, followed by the other 2 animals at 6 weeks. The device was designed to
      simultaneously distract the periosteum at different rates along its inclined
      surface. Newly formed bone was histologically and radiographically evaluated.
      RESULTS: The new device effectively induced osteogenesis and successfully
      distracted the soft tissue after 6 weeks in a rabbit model. CONCLUSIONS: The new
      device is slim, and the procedure is straightforward. Thus, periosteal
      distraction with this device can potentially be used for vertical and horizontal
      ridge augmentation in the oral cavity. In addition, the results suggest that
      connective tissue growth in the distraction site might be controlled by reducing
      the speed of periosteal distraction.

PMID- 22374067
TI  - Dual midfacial distraction osteogenesis for Crouzon syndrome: long-term follow-up
      study for relapse and growth.
AB  - PURPOSE: Rigid external distraction osteogenesis is regarded as a standard
      treatment for congenital midfacial hypoplasia. However, external distraction for
      the upper portion of the midface is not as effective and tends to rotate the
      midfacial segment in a counterclockwise direction. Moreover, patients poorly
      tolerate it because of the device's bulkiness. To prevent such drawbacks of an
      external distractor, both external and internal distractors were synchronously
      applied to patients with Crouzon syndrome. PATIENTS AND METHODS: In 6 patients
      with Crouzon syndrome in whom a dual-distraction technique was applied,
      distraction of the midfacial region was performed for up to a mean length of 15.3
      mm. The external distractor was removed after a 1-month consolidation period, but
      the internal distractor was maintained for more than 6 months. The degree of
      advancement of the midface and ossification was measured with lateral
      cephalometry and 3-dimensional computed tomography imaging, respectively.
      RESULTS: At long-term follow-up (mean, 4.6 years), the facial contours retained
      the initial distraction geometry with almost no relapse, showing that the ideal
      facial contour and occlusion could be obtained. Bone deposition was found to be
      continually progressing even 6 months postoperatively, and more than 6 months of
      consolidation was required for complete ossification that mainly occurred in the
      pterygomaxillary junction and lateral orbital wall. CONCLUSIONS: The dual
      distraction technique can induce balanced growth without the recurrence of
      hypoplasia, and it may eventually yield satisfactory outcomes in Crouzon
      syndrome.

PMID- 22374068
TI  - Aggressive olfactory neuroblastoma invading the oral cavity: report of a rare
      case and review of the literature.

PMID- 22374069
TI  - Interaction of monogalactosyldiacylglycerol with cytochrome b6f complex in
      surface films.
AB  - The interaction of monogalactosyldiacylglycerol (MGDG) with cytochrome b(6)f
      complex (cyt b(6)f), a major component of the photosynthetic apparatus, was
      studied in Langmuir monolayers during compression/expansion cycling and at
      constant surface pressure mode. The surface pressure/area isotherms of the mixed
      films were analyzed in terms of surface compressional modulus and two-dimensional
      virial equation of state. The morphology and the surface potential of the
      monolayers were monitored by Brewster angle microscopy and vibrating plate sensor
      respectively. Our results suggested that there is a specific interaction between
      MGDG and cyt b(6)f which resulted in depletion of lipid molecules from the
      interface. The current work sheds light on the still unclear question how b(6)f
      complex gets in touch with the major compound of the thylakoid membranes, the non
      charged lipid MGDG. The interaction occured even at very low sub-nanomolar
      concentration of the complex. This effect most probably could be attributed to
      hydrogen bonding between the galactose headgroup of the lipid and the protein
      moiety of cyt b(6)f.

PMID- 22374070
TI  - TAZ is downregulated by dexamethasone during the differentiation of 3T3-L1
      preadipocytes.
AB  - TAZ (transcriptional co-activator with PDZ binding motif) is a transcriptional
      modulator of mesenchymal stem cell differentiation. We have found that TAZ was
      expressed in postconfluent 3T3-L1 preadipocytes and downregulated during
      differentiation. Downregulation of TAZ was specifically mediated by dexamethasone
      (DEX), one component of induction cocktails routinely used in adipocyte
      differentiation. DEX repressed the transcription of TAZ by direct binding of the
      glucocorticoid receptor (GR) to the GR binding element in its promoter. More
      importantly, overexpression of TAZ inhibited adipogenesis and promoted the trans
      differentiation of preadipocytes into osteocytes. This establishes a new
      functional interaction between DEX and TAZ that contributes to the mechanism of
      adipogenesis.

PMID- 22374072
TI  - Pulmonary aspergilloma in patient with anorexia nervosa: case report.
AB  - A 31-year old female with anorexia nervosa was referred to the Department of
      General Surgical Science at Gunma University for a surgical resection of a
      pulmonary aspergilloma. The patient had received treatment for anorexia nervosa
      at the Department of Psychiatry of the Hospital of Gunma University Graduate
      School of Medicine. A chest radiograph showed an infiltrative shadow with apical
      pleural thickening in the left upper lung field. A contrast enhanced computed
      tomography showed an irregular mass shadow with cavity formation that involved
      spherical clusters in the left upper lobe. The patient was diagnosed with
      pulmonary aspergilloma by serological studies and radiological features. A
      pulmonary segmentectomy of the left apical segment (S1 + 2) through a lateral
      thoracotomy was successfully performed. She had an uneventful postoperative
      recovery, and the final histopathological examination confirmed the diagnosis of
      pulmonary aspergilloma. This is a rare case study of a young female patient with
      anorexia nervosa who developed pulmonary aspergilloma.

PMID- 22374071
TI  - The effects of hypoxia acclimation, exercise training and fasting on swimming
      performance in juvenile qingbo (Spinibarbus sinensis).
AB  - To investigate the effects of hypoxia acclimation, exercise training and fasting
      on the swimming performance of juvenile qingbo (Spinibarbus sinensis), we
      measured the critical swimming speed (U (crit)), resting and excess post-exercise
      oxygen consumption (EPOC) of control, hypoxia-acclimated, exercise-acclimated and
      fasting fish at 25 degrees C. The muscle and plasma metabolites before and after
      a bout of exhaustive exercise (produced by chasing) were also measured. The fish
      were acclimated to hypoxia (48 h at 1.0 mg L(-1), 12.5% air saturation), exercise
      training (2 weeks at 60% of U (crit), 6 h daily) or fasting (2 weeks). All
      treatments resulted in significantly lower resting oxygen consumption ([Formula:
      see text]O(2rest)) but had no effect on the magnitude of EPOC. Hypoxia
      acclimation had no effect on U (crit) or peak post-exercise oxygen consumption
      ([Formula: see text]O(2peak)) but produced a higher depletion of muscle
      [glycogen] post-chasing (P < 0.05). Exercise training produced a significant
      increase in U (crit), higher liver [glycogen] pre-chasing and higher depletion of
      muscle [glycogen] post-chasing. Fasting resulted in a significant decrease in U
      (crit), [Formula: see text]O(2peak), muscle and liver [glycogen]. These results
      suggested that hypoxia acclimation had no effect on swimming performance in
      qingbo. Exercise training produced improved swimming performance by increasing
      the stored energy and the metabolic capacity of muscle. Fasting had a profound
      effect on swimming performance through both decreased respiratory capacity and a
      depleted energy store.

PMID- 22374073
TI  - Rib fixation for severe chest deformity due to multiple rib fractures.
AB  - The operative indications for rib fracture repair have been a matter of debate.
      However, several reports have suggested that flail chest, pain on respiration,
      and chest deformity/defect are potential conditions for rib fracture repair. We
      describe our experience of rib fixation in a patient with severe chest deformity
      due to multiple rib fractures. A 70-year-old woman was admitted with right-sided
      multiple rib fractures (2nd to 7th) and marked chest wall deformity without
      flailing caused by an automobile accident. Collapse of the chest wall was
      observed along the middle anterior axillary line. At 11 days after the injury,
      surgery was performed to repair the chest deformity, as it was considered to pose
      a risk of restrictive impairment of pulmonary function or chronic intercostal
      pain in the future. Operative findings revealed marked displacement of the
      superior 4 ribs, from the 2nd to the 5th, and collapse of the osseous chest wall
      towards the thoracic cavity. After exposure of the fracture regions, ribs
      fixations were performed using rib staplers. The total operation time was 90
      minutes, and the collapsed portion of the chest wall along the middle anterior
      axillary line was reconstructed successfully.

PMID- 22374074
TI  - Multiple segmentectomy for synchronous multiple small peripheral lung cancers:
      report of two cases.
AB  - Treatment strategies for synchronous, multiple peripheral lung cancers remain
      controversial. Bilobectomy for multiple lung cancers could cause pulmonary
      function impairment. We report two patients with synchronous multiple peripheral
      non-small cell lung cancers, who underwent multiple segmentectomy simultaneously.
      This is the first report of consecutive segmentectomy of two segments.

PMID- 22374075
TI  - Successful resection of stage IV non-small cell lung cancer with muscle
      metastasis as the initial manifestation: a case report.
AB  - Here, we report a rare case of a 39-year-old male who presented with left forearm
      pain and swelling as the initial manifestation of non-small cell lung cancer
      (NSCLC). The patient underwent chemoradiotherapy followed by surgical resection
      of the primary lesion as a salvage treatment. Four years and 7 months after his
      first presentation, the patient is alive with no symptoms of recurrence or
      metastasis. Although the optimal treatment for skeletal muscle metastasis from
      NSCLC has not been determined, aggressive treatment for the primary and the
      solitary metastatic lesion could be considered as a potentially successful
      treatment option.

PMID- 22374076
TI  - Aortic valve-sparing operation after correction of heart displacement due to
      pectus excavatum using Nuss procedure in a Marfan syndrome patient.
AB  - Cardiovascular surgery in the setting of chest wall deformities is a clinical
      challenge. Pectus excavatum, for example, can cause heart displacement to the
      left thoracic cavity, following the poor operative field. This report highlights
      a case in which a successful aortic valve-sparing operation via conventional
      median sternotomy after correction of the heart displacement due to pectus
      excavatum using Nuss procedure in Marfan syndrome. This technique can be one
      surgical option in Marfan syndrome patients with pectus excavatum and thoracic
      aortic aneurysm under close follow up.

PMID- 22374078
TI  - Epigenetic modifications and chromosome conformations of the beta globin locus
      throughout development.
AB  - Human embryonic stem cells provide an alternative to using human embryos for
      studying developmentally regulated gene expression. The co-expression of high
      levels of embryonic epsilon and fetal gamma globin by the hESC-derived
      erythroblasts allows the interrogation of epsilon globin regulation at the
      transcriptional and epigenetic level which could only be attained previously by
      studying cell lines or transgenic mice. In this study, we compared the histone
      modifications across the beta globin locus of the undifferentiated hESCs and hESC
      , FL-, and mobilized PB CD34(+) cells-derived erythroblasts, which have distinct
      globin expression patterns corresponding to their developmental stages. We
      demonstrated that the histone codes employed by the beta globin locus are
      conserved throughout development. Furthermore, in spite of the close proximity of
      the epsilon globin promoter, as compared to the beta or gamma globin promoter,
      with the LCR, a chromatin loop was also formed between the LCR and the active
      epsilon globin promoter, similar to the loop that forms between the beta or gamma
      globin promoters and the LCR, in contrary to the previously proposed tracking
      mechanism. 

PMID- 22374079
TI  - Hematopoietic MyD88-adaptor protein acts as a natural defense mechanism for
      cognitive deficits in Alzheimer's disease.
AB  - Accumulating evidence supports a critical role of Toll-like receptors in the
      clearance of Amyloid beta (Abeta) by microglial cells. Myeloid differentiation
      factor 88 (MyD88) is an adaptor protein that bridges the intracellular signal to
      nucleus for most of these innate immune receptors. We investigated here the role
      of competent MyD88 hematopoietic stem cells on the cognitive decline of a mouse
      model of Alzheimer's disease (AD). We generated classical chimeric mouse models
      using irradiation and transplantation of wild type GFP cells and MyD88-deficient
      cells. Transplantation of GFP cells essentially rescued the cognitive impairment,
      whereas MyD88-deficient cells significantly accelerated memory deficits of
      APP(swe)/PS1 mice. Moreover, we found that monocytes and microglia deficient for
      MyD88 exhibit a functionally impaired phagocytic reaction to Abeta.

PMID- 22374080
TI  - Pharmacovigilance practice and risk control of Traditional Chinese Medicine drugs
      in China: current status and future perspective.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM), including
      Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important
      role in health protection and disease control for thousands of years in China.
      Relying on natural products, mainly of herbal origin, used either as raw
      materials for decoction, as prepared herbal medicines or as formulated
      traditional medicines, TCM is still widely accepted by Chinese people, especially
      for chronic diseases treatment. This extensive use warrants safety measures and
      so TCM drug safety monitoring and risk management are becoming increasingly
      important tasks for the Chinese State Food and Drug Administration (SFDA).
      METHODS: The Adverse Drug Reaction (ADR) monitoring system in China was
      established both for western and TCM drugs in 1989 as a voluntary reporting
      system with a National Center collecting and compiling reports. Serious or multi
      case reports on individual TCM drug or formulated products are detailed in the
      Chinese ADR Information Bulletin to inform the public and Drug Administrative
      authorities for risk management. RESULTS: About 10-15% of the ADR reports
      received by the National Center are related to TCM drugs and mainly pertaining to
      the formulated products. In certain cases, the suspension of a particular TCM
      preparation is decided by SFDA China. CONCLUSION: The model of safety monitoring
      and risk management of TCM drugs is still under exploration. Indeed, the
      characteristics and risk factors associated with these drugs require both proper
      understanding and control of the risk by strengthening standardization of
      clinical applications, basic science research, quality control in manufacturing,
      exploration of the actives monitoring methodology and enhancement of
      international communication and cooperation.

PMID- 22374081
TI  - Gastroprotective activities of Turnera diffusa Willd. ex Schult. revisited: Role
      of arbutin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Turnera diffusa Willd. ex Schult. has been used
      for the treatment of several human disorders including peptic ulcer. OBJECTIVES
      OF THE STUDY: The current study is an attempt to evaluate the anti-ulcerogenic
      activities of arbutin, a major constituent of Turnera diffusa on two ulcer
      models. The possible involvement of lipid peroxidation, nitric oxide, IL-6, IL
      10, TNF-alpha and mucus barrier mechanism has been investigated. MATERIALS AND
      METHODS: Effects of arbutin on ulcer index, gastric juice acidity, mucus content
      and histochemistry, gross and histological gastric lesions, nitric oxide,
      cytokines levels (IL-6, IL-10 and TNF-alpha), and thiobarbituric acid reactive
      substances (TBARS), were evaluated in aspirin or ethanol-induced ulcer in vivo.
      Acute toxicity of arbutin was also examined in rodent model. MTT assay was used
      to assess the cytotoxicity of the compound on normal liver cells (WRL-68).
      RESULTS: Pre-treatment with arbutin or omeprazole protected the gastric mucosa as
      seen by reduction in ulcer area and mucosal content, reduced or absence of edema,
      inflammation and leucocytes infiltration on both models. Arbutin significantly
      (P<0.05) lowered the elevated TBARS level into gasteric homogenate. Arbutin did
      not produce significant inhibition of NO. This natural compound has modulated the
      levels of interleukin-6, interleukin-10 and TNF-alpha. No in vitro or in vivo
      toxicities for arbutin were observed. CONCLUSION: Thus it can be concluded that
      Turnera diffusa possesses anti-ulcer activity, which could be attributed to lipid
      peroxidation inhibitory, immuno modulatory and anti-oxidant mechanisms of arbutin
      but not to the intervention with nitric oxide inflammation pathway.

PMID- 22374082
TI  - Effects of an Atractylodes lancea rhizome extract and a volatile component beta
      eudesmol on gastrointestinal motility in mice.
AB  - AIM OF THE STUDY: The rhizomes of Atractylodes lancea DC (Compositae) are used
      clinically to treat gastrointestinal symptoms, including functional dyspepsia and
      gastroparesis, in China and Japan, but their influence and mechanism on
      gastrointestinal motility are not yet proven in detail. MATERIALS AND METHODS:
      This study examined the effects of an Atractylodes lancea extract, and isolated
      beta-eudesmol, on gastric emptying and small intestinal motility in atropine-,
      dopamine-, and 5-hydroxytryptamine (5-HT)-treated mice. RESULTS AND CONCLUSIONS:
      The extract (500 or 1000mg/kg) and beta-eudesmol (50 or 100mg/kg), as well as
      itopride hydrochloride (a dopamine D(2) receptor antagonist, 10 or 50mg/kg),
      stimulated small intestinal motility in normal mice. They inhibited reductions in
      gastric emptying and gastrointestinal motility induced by dopamine (1mg/kg,
      intraperitoneal injection, ip). The extract (1000mg/kg) and beta-eudesmol
      (100mg/kg) inhibited the atropine-induced decrease in small intestinal motility,
      but not gastric emptying. Furthermore, the extract (500 or 1000mg/kg) and beta
      eudesmol (25, 50, or 100mg/kg) inhibited reductions in gastric emptying and small
      intestinal motility caused by 5-HT (4mg/kg, ip) or the 5-HT(3) receptor agonist 1
      (3-chlorophenyl) biguanide (0.5mg/kg, ip), but not a 5-HT(2C) receptor agonist.
      These findings suggest that the extract of Atractylodes lancea and beta-eudesmol
      may stimulate gastric emptying or small intestinal motility by inhibiting the
      dopamine D(2) receptor and 5-HT(3) receptor.

PMID- 22374083
TI  - [Image-guided radiation therapy].
AB  - Radiotherapy technology has improved rapidly over the past two decades. New
      imaging modalities, such as positron emission (computed) tomography (PET, PET-CT)
      and high-resolution morphological and functional magnetic resonance imaging (MRI)
      have been introduced into the treatment planning process. Image-guided radiation
      therapy (IGRT) with 3D soft tissue depiction directly imaging target and normal
      structures, is currently replacing patient positioning based on patient surface
      markers, frame-based intracranial and extracranial stereotactic treatment and
      partially also 2D field verification methods. On-line 3D soft tissue-based
      position correction unlocked the full potential of new delivery techniques, such
      as intensity-modulated radiotherapy, by safely delivering highly conformal dose
      distributions that facilitate dose escalation and hypofractionation. These
      strategies have already resulted in better clinical outcomes, e.g. in prostate
      and lung cancer and are expected to further improve radiotherapy results.

PMID- 22374084
TI  - [Functional magnetic resonance imaging for evaluation of radiation-induced renal
      damage].
AB  - The diagnosis of radiation-induced (especially chronic) renal alterations/damage
      is difficult and currently relies primarily on clinical evaluation. The
      importance of renal diagnostic evaluation will increase continuously due to the
      increasing number of long-term survivors after radiotherapy. This article
      evaluates the potentia diagnostic contribution of magnetic resonance (MR) imaging
      with a focus on functional MRI. The following functional MRI approaches are
      briefly presented and evaluated: blood oxygenation level-dependent imaging
      (BOLD), diffusion-weighted imaging (DWI) or diffusion tensor imaging (DTI), MR
      perfusion measurements and (23)Na imaging. In summary, only DWI and contrast
      enhanced MR perfusion currently seem to be suitable approaches for a broader,
      clinical implementation. However, up to now valid data from larger patient
      studies are lacking for both techniques in regard to radiation-induced renal
      alterations. The BOLD and (23)Na imaging procedures have a huge potential but are
      currently neither sufficiently evaluated with regard to radiation-induced renal
      alterations nor technically simple and reliable for implementation into the
      clinical routine.

PMID- 22374085
TI  - [Compatibility of family and profession. Survey of radiologists and medical
      technical personnel in clinics with different organizations].
AB  - PURPOSE: The compatibility of family and profession is especially difficult for
      employees in medical professions because of shift work and overtime. It seems
      that in the future women are going to represent the majority of medical
      professionals in Germany. Hence, with the forthcoming lack of physicians in
      Germany social aspects will also play a greater role in the choice of the place
      of employment. Therefore a statistical survey was made among employees on how
      they judge the compatibility of family and job and what they would like to
      improve. MATERIALS AND METHODS: From autumn 2009 until spring 2010 a total of 115
      questionnaires were distributed to 8 different academic radiology departments.
      The anonymous questionnaire with partially open, partially graded questions and
      partially multiple answer questions was designed with the help of an expert for
      statistics and analytics and included questions about the employment and family
      situation, plans for the future, requested flexible working hours and childcare
      models, as well as ideas for improvement. Of the questionnaires 87 were analyzed
      with a specially designed access database using, for example descriptive
      statistics and histogram analyses. RESULTS: Of the interviewees 68% were female
      and 31% were male (1% not significant n.s.), 46% had children and 49% were
      childless (5% n.s.), 63% were medical doctors, 33% radiographers (3% other) and
      82% worked full-time. Of the male respondents with children 42% indicated that
      their spouse was at home, 18% of female respondents with children indicated that
      their spouse was at home and only mothers worked part-time. Of the male
      respondents 73% would like to take parental leave, 44% of all respondents (70% of
      the male respondents and 34% of the female respondents) agreed that radiology is
      more compatible with family than other medical disciplines and 87% would like to
      have a childcare possibility in close proximity to the working place.
      DISCUSSION/CONCLUSIONS: In most of the families the classic role model prevails,
      although women are well-educated and men also set a high value on the
      compatibility of family and profession and would like to take parental leave and
      work flexible working hours. This is a chance especially for radiology.

PMID- 22374086
TI  - Ca(2+) signalling by IP(3) receptors.
AB  - The Ca(2) (+) signals evoked by inositol 1,4,5-trisphosphate (IP(3)) are built
      from elementary Ca(2) (+) release events involving progressive recruitment of
      IP(3) receptors (IP(3)R), intracellular Ca(2) (+) channels that are expressed in
      almost all animal cells. The smallest events ('blips') result from opening of
      single IP(3)R. Larger events ('puffs') reflect the near-synchronous opening of a
      small cluster of IP(3)R. These puffs become more frequent as the stimulus
      intensity increases and they eventually trigger regenerative Ca(2) (+) waves that
      propagate across the cell. This hierarchical recruitment of IP(3)R is important
      in allowing Ca(2) (+) signals to be delivered locally to specific target proteins
      or more globally to the entire cell. Co-regulation of IP(3)R by Ca(2) (+) and
      IP(3), the ability of a single IP(3)R rapidly to mediate a large efflux of Ca(2)
      (+) from the endoplasmic reticulum, and the assembly of IP(3)R into clusters are
      key features that allow IP(3)R to propagate Ca(2) (+) signals regeneratively. We
      review these properties of IP(3)R and the structural basis of IP(3)R behavior.

PMID- 22374087
TI  - Phosphoinositide signaling during membrane transport in Saccharomyces cerevisiae.
AB  - Phosphatidylinositol (PI) is distinct from other phospholipids, possessing a head
      group that can be modified by phosphorylation at multiple positions to generate
      unique signaling molecules collectively known as phosphoinositides. The set of
      kinases and phosphatases that regulate PI metabolism are conserved throughout
      eukaryotic evolution, and numerous studies have demonstrated that
      phosphoinositides regulate a diverse spectrum of cellular processes, including
      vesicle transport, cell proliferation, and cytoskeleton organization. Over the
      past two decades, nearly all PI derivatives have been shown to interact directly
      with cellular proteins to affect their localization and/or activity.
      Additionally, there is growing evidence, which suggests that phosphoinositides
      may also affect local membrane topology. Here, we focus on the role of
      phosphoinositides in membrane trafficking and underscore the significant role
      that yeast has played in the field.

PMID- 22374089
TI  - Role of PI(4,5)P(2) in vesicle exocytosis and membrane fusion.
AB  - A role for phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in membrane fusion
      was originally identified for regulated dense-core vesicle exocytosis in
      neuroendocrine cells. Subsequent studies demonstrated essential roles for
      PI(4,5)P(2) in regulated synaptic vesicle and constitutive vesicle exocytosis.
      For regulated dense-core vesicle exocytosis, PI(4,5)P(2) appears to be primarily
      required for priming, a stage in vesicle exocytosis that follows vesicle docking
      and precedes Ca(2) (+)-triggered fusion. The priming step involves the
      organization of SNARE protein complexes for fusion. A central issue concerns the
      mechanisms by which PI(4,5)P(2) exerts an essential role in membrane fusion
      events at the plasma membrane. The observed microdomains of PI(4,5)P(2) in the
      plasma membrane of neuroendocrine cells at fusion sites has suggested possible
      direct effects of the phosphoinositide on membrane curvature and tension. More
      likely, PI(4,5)P(2) functions in vesicle exocytosis as in other cellular
      processes to recruit and activate PI(4,5)P(2)-binding proteins. CAPS and Munc13
      proteins, which bind PI(4,5)P(2) and function in vesicle priming to organize
      SNARE proteins, are key candidates as effectors for the role of PI(4,5)P(2) in
      vesicle priming. Consistent with roles prior to fusion that affect SNARE
      function, subunits of the exocyst tethering complex involved in constitutive
      vesicle exocytosis also bind PI(4,5)P(2). Additional roles for PI(4,5)P(2) in
      fusion pore dilation have been described, which may involve other PI(4,5)P(2)
      binding proteins such as synaptotagmin. Lastly, the SNARE proteins that mediate
      exocytic vesicle fusion contain highly basic membrane-proximal domains that
      interact with acidic phospholipids that likely affect their function.

PMID- 22374091
TI  - Phosphatidylinositol 4, 5 bisphosphate and the actin cytoskeleton.
AB  - Dynamic changes in PM PIP(2) have been implicated in the regulation of many
      processes that are dependent on actin polymerization and remodeling. PIP(2) is
      synthesized primarily by the type I phosphatidylinositol 4 phosphate 5 kinases
      (PIP5Ks), and there are three major isoforms, called a, b and g. There is
      emerging evidence that these PIP5Ks have unique as well as overlapping functions.
      This review will focus on the isoform-specific roles of individual PIP5K as they
      relate to the regulation of the actin cytoskeleton. We will review recent
      advances that establish PIP(2) as a critical regulator of actin polymerization
      and cytoskeleton/membrane linkages, and show how binding of cytoskeletal proteins
      to membrane PIP(2) might alter lateral or transverse movement of lipids to affect
      raft formation or lipid asymmetry. The mechanisms for specifying localized
      increase in PIP(2) to regulate dynamic actin remodeling will also be discussed.

PMID- 22374088
TI  - Phosphoinositides in the mammalian endo-lysosomal network.
AB  - The endo-lysosomal system is an interconnected tubulo-vesicular network that acts
      as a sorting station to process and distribute internalised cargo. This network
      accepts cargoes from both the plasma membrane and the biosynthetic pathway, and
      directs these cargos either towards the lysosome for degradation, the peri
      nuclear recycling endosome for return to the cell surface, or to the trans-Golgi
      network. These intracellular membranes are variously enriched in different
      phosphoinositides that help to shape compartmental identity. These lipids act to
      localise a number of phosphoinositide-binding proteins that function as sorting
      machineries to regulate endosomal cargo sorting. Herein we discuss regulation of
      these machineries by phosphoinositides and explore how phosphoinositide-switching
      contributes toward sorting decisions made at this platform.

PMID- 22374092
TI  - Phosphoinositides in chemotaxis.
AB  - Phosphatidylinositol lipids generated through the action of phosphinositide 3
      kinase (PI3K) are key mediators of a wide array of biological responses. In
      particular, their role in the regulation of cell migration has been extensively
      studied and extends to amoeboid as well as mesenchymal migration. Through the
      emergence of fluorescent probes that target PI3K products as well as the use of
      specific inhibitors and knockout technologies, the spatio-temporal distribution
      of PI3K products in chemotaxing cells has been shown to represent a key anterior
      polarity signal that targets downstream effectors to actin polymerization. In
      addition, through intricate cross-talk networks PI3K products have been shown to
      regulate signals that control posterior effectors. Yet, in more complex
      environments or in conditions where chemoattractant gradients are steep, a
      variety of cell types can still chemotax in the absence of PI3K signals. Indeed,
      parallel signal transduction pathways have been shown to coordinately regulate
      cell polarity and directed movement. In this chapter, we will review the current
      role PI3K products play in the regulation of directed cell migration in various
      cell types, highlight the importance of mathematical modeling in the study of
      chemotaxis, and end with a brief overview of other signaling cascades known to
      also regulate chemotaxis.

PMID- 22374093
TI  - Phosphoinositides in Golgi complex function.
AB  - The Golgi complex is a ribbon-like organelle composed of stacks of flat cisternae
      interconnected by tubular junctions. It occupies a central position in the
      endomembrane system as proteins and lipids that are synthesized in the
      endoplasmic reticulum (ER) pass through the Golgi complex to undergo biosynthetic
      modification (mainly glycosylation) and to be sorted to their final destinations.
      In addition the Golgi complex possesses a number of activities, apparently not
      directly connected with its main role in trafficking and sorting, which have been
      recently reviewed in Wilson et al. 2011. In spite of the constant massive flux of
      material the Golgi complex maintains its identity and phosphoinositides (PIs),
      among other factors, play a central role in this process. The active metabolism
      of PIs at the Golgi is necessary for the proper functioning of the organelle both
      in terms of membrane trafficking/sorting and its manifold metabolic and
      signalling activities. Phosphatidylinositol 4-phosphate (PtdIns4P), in
      particular, is responsible for the recruitment of numerous cytosolic proteins
      that recognise and bind PtdIns4P via specific lipid-binding domains. In this
      chapter we will summarize the findings that have contributed to our current
      understanding of the role of PIs in the biology of the Golgi complex in terms of
      the regulation of PI metabolism and the functional roles and regulation of
      PtdIns4P effectors.

PMID- 22374095
TI  - Phosphoinositide sensitivity of ion channels, a functional perspective.
AB  - Phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P(2)] are required for the activity of many different ion channels.
      This chapter will highlight various aspects of this paradigm, by discussing
      current knowledge on four different ion channel families: inwardly rectifying
      K(+) (Kir) channels, KCNQ voltage gated K(+) channels, voltage gated Ca(2+)
      (VGCC) channels and Transient Receptor Potential (TRP) channels. Our main focus
      is to discuss functional aspects of this regulation, i.e. how changes in the
      concentration of PtdIns(4,5)P(2) in the plasma membrane upon phospholipase C
      activation may modulate the activity of ion channels, and what are the major
      determinants of this regulation. We also discuss how channels act as coincidence
      detectors sensing phosphoinositide levels and other signalling molecules. We also
      briefly discuss the available methods to study phosphoinositide regulation of ion
      channels, and structural aspects of interaction of ion channel proteins with
      these phospholipids. Finally, in several cases the effect of PtdIns(4,5)P(2) is
      more complex than a simple dependence of ion channel activity on the lipid, and
      we will discuss some these complexities.

PMID- 22374096
TI  - Nuclear phosphoinositides: location, regulation and function.
AB  - Lipid signalling in human disease is an important field of investigation and
      stems from the fact that phosphoinositide signalling has been implicated in the
      control of nearly all the important cellular pathways including metabolism, cell
      cycle control, membrane trafficking, apoptosis and neuronal conduction. A
      distinct nuclear inositide signalling metabolism has been identified, thus
      defining a new role for inositides in the nucleus, which are now considered
      essential co-factors for several nuclear processes, including DNA repair,
      transcription regulation, and RNA dynamics. Deregulation of phoshoinositide
      metabolism within the nuclear compartment may contribute to disease progression
      in several disorders, such as chronic inflammation, cancer, metabolic, and
      degenerative syndromes. In order to utilize these very druggable pathways for
      human benefit there is a need to identify how nuclear inositides are regulated
      specifically within this compartment and what downstream nuclear effectors
      process and integrate inositide signalling cascades in order to specifically
      control nuclear function. Here we describe some of the facets of nuclear
      inositide metabolism with a focus on their relationship to cell cycle control and
      differentiation.

PMID- 22374097
TI  - Phosphoinositides and cellular pathogens.
AB  - Phosphoinositides are considered as highly dynamic players in the spatiotemporal
      organization of key signaling pathways, actin cytoskeleton rearrangements,
      establishment of cell polarity and intracellular vesicle trafficking. Their
      metabolism is accurately controlled and mutations in several phosphoinositide
      metabolizing enzymes take part in the development of human pathologies.
      Interestingly, evidence is accumulating that modulation of the phosphoinositide
      metabolism is critical for pathogenicity and virulence of many human pathogens.
      Given the importance of phosphoinositides, which link membrane and cytoskeleton
      dynamics to cell responses, it is not surprising that many invasive pathogens
      hijack their metabolism as part of their strategies to establish infection. In
      fact, according to their lifestyle, cellular pathogens use the phosphoinositide
      metabolism in order to trigger their uptake in nonphagocytic cells and/or
      modulate the maturation of the pathogen-containing vacuole to establish their
      replicative niche or escape in the cytosol and promote host cell survival. The
      last two decades have been marked by the discovery of different tactics used by
      cellular pathogens to modulate the phosphoinositide metabolism as part of their
      strategies to survive, proliferate and disseminate in a hostile environment.

PMID- 22374094
TI  - Sec14 like PITPs couple lipid metabolism with phosphoinositide synthesis to
      regulate Golgi functionality.
AB  - An interface coordinating lipid metabolism with proteins that regulate membrane
      trafficking is necessary to regulate Golgi morphology and dynamics. Such an
      interface facilitates the membrane deformations required for vesicularization,
      forms platforms for protein recruitment and assembly on appropriate sites on a
      membrane surface and provides lipid co-factors for optimal protein activity in
      the proper spatio-temporally regulated manner. Importantly, Sec14 and Sec14-like
      proteins are a unique superfamily of proteins that sense specific aspects of
      lipid metabolism, employing this information to potentiate phosphoinositide
      production. Therefore, Sec14 and Sec14 like proteins form central conduits to
      integrate multiple aspects of lipid metabolism with productive phosphoinositide
      signaling.

PMID- 22374090
TI  - Role of phosphoinositides at the neuronal synapse.
AB  - Synaptic transmission is amongst the most sophisticated and tightly controlled
      biological phenomena in higher eukaryotes. In the past few decades, tremendous
      progress has been made in our understanding of the molecular mechanisms
      underlying multiple facets of neurotransmission, both pre- and postsynaptically.
      Brought under the spotlight by pioneer studies in the areas of secretion and
      signal transduction, phosphoinositides and their metabolizing enzymes have been
      increasingly recognized as key protagonists in fundamental aspects of
      neurotransmission. Not surprisingly, dysregulation of phosphoinositide metabolism
      has also been implicated in synaptic malfunction associated with a variety of
      brain disorders. In the present chapter, we summarize current knowledge on the
      role of phosphoinositides at the neuronal synapse and highlight some of the
      outstanding questions in this research field.

PMID- 22374099
TI  - Cell signalling by inositol pyrophosphates.
AB  - Inositol serves as a module for the generation of a high level of molecular
      diversity through the combinatorial attachment and removal of phosphate groups.
      The array of potential inositol-containing molecules is further expanded by the
      generation of diphospho inositol polyphosphates, commonly referred as inositol
      pyrophosphates. All eukaryotic cells possess inositol pyrophosphates containing
      one or more diphospho- moieties. The metabolism of this class of molecules is
      highly dynamic, and the enzymes responsible for their metabolism are evolutionary
      conserved. This new, exciting class of molecules are uniquely chracterized by a
      high energetic diphospho- bound that is able to participate in phosphotrasfer
      reactions thereby generating pyrophosphorylation of protein. However, allosteric
      mechanisms of action have been also proposed. In the past decade several
      disparate nuclear and cytoplasmic functions have been attributed to inositol
      pyrophosphates, ranging from intracellular trafficking to telomere length control
      and from regulating apoptotic process to stimulating insulin secretion. The
      extraordinary range of cellular function controlled by inositol pyrophosphate
      underline their great importance.

PMID- 22374100
TI  - Spatial distribution and molecular characterization of Anopheles nivipes and
      Anopheles philippinensis (Diptera: Culicidae) in north-east India.
AB  - Anopheles philippinensis-nivipes species of mosquitoes are considered secondary
      malaria vectors in the north-east India. However, difficulty in separating An.
      philippinensis and An. nivipes accurately on the basis of morphological
      identification, due to the overlapping female wing characters, has led to the
      paucity of information on their spatial distribution and vectorial importance,
      essential for understanding malaria disease epidemiology in areas under their
      influence. In view of this a study was undertaken to generate authentic
      information on distribution of An. philippinensis and An. nivipes in the north
      east India using molecular tools. Between the two, An. nivipes was recorded as
      the dominant species in Assam, and Nagaland states whereas An. philippinensis was
      found predominant in the state of Mizoram and Arunachal Pradesh. Species
      differentiation based on female wing characters proved wrong in about 74%
      specimens of An. philippinensis but found accurate in case of An. nivipes. No
      intra-specific variation in second internal transcribed spacer (ITS2) region of
      ribosomal DNA(r-DNA) in either An. nivipes or An. philippinensis from different
      geographical areas of north-east India was noted.

PMID- 22374098
TI  - Defining signal transduction by inositol phosphates.
AB  - Ins(1,4,5)P(3) is a classical intracellular messenger: stimulus-dependent changes
      in its levels elicits biological effects through its release of intracellular
      Ca(2+) stores. The Ins(1,4,5)P(3) response is "switched off" by its metabolism to
      a range of additional inositol phosphates. These metabolites have themselves come
      to be collectively described as a signaling "family". The validity of that latter
      definition is critically examined in this review. That is, we assess the strength
      of the hypothesis that Ins(1,4,5)P(3) metabolites are themselves "classical"
      signals. Put another way, what is the evidence that the biological function of a
      particular inositol phosphate depends upon stimulus dependent changes in its
      levels? In this assessment, examples of an inositol phosphate acting as a
      cofactor (i.e. its function is not stimulus-dependent) do not satisfy our
      signaling criteria. We conclude that Ins(3,4,5,6)P(4) is, to date, the only
      Ins(1,4,5)P(3) metabolite that has been validated to act as a second messenger.

PMID- 22374101
TI  - TaqMan hydrolysis probe based real time PCR for detection and quantitation of
      camelpox virus in skin scabs.
AB  - The study describes the development of TaqMan hydrolysis probe based real time
      PCR (rt-PCR) assay targeting the ankyrin repeat protein (C18L) gene sequences for
      the detection and quantitation of camelpox virus (CMLV) nucleic acid and its
      comparison with established conventional and SYBR green rt-PCR assays. The assay
      was specific with an efficiency of 99.4%. The analytical sensitivity was 4 * 101
      and 0.35 in terms of copy number and picogram of virus genomic DNA, respectively.
      The assay was linear with an acceptable intra (0.9-2.83% and 0.9-2.3%) and inter
      assay (0.46-2.3% and 0.9-3.3) variations, when standard plasmid DNA and genomic
      DNA from purified CMLV respectively were tested. The assay was rapid, specific
      and sensitive as that of SYBR green and 1000 times more sensitive than the
      conventional PCR. It is suitable for the detection of CMLV nucleic acid directly
      from clinical samples. Further, the assay was evaluated using cell culture
      adapted CMLV isolates (n=11) and clinical samples (n=23) from camels and humans
      suspected of camelpox. This is an improved technique over conventional and SYBR
      green rt-PCR methods for the detection and quantitation of CMLV from skin scabs.

PMID- 22374102
TI  - Detection of influenza A viruses with a portable real-time PCR instrument.
AB  - Timely identification of respiratory pathogens is essential for appropriate
      patient care and cohorting. In order to do rapid identification-technology near
      the patient we utilized the field-deployable RAZOR EX-thermocycler with a reverse
      transcription real-time PCR assay that detects all subtypes of influenza A virus.
      In addition, we developed a RT PCR assay for specific detection of influenza
      A(H1N1)pdm09 virus. These assays amplified segments of the matrix (M)- and the
      hemagglutinin (HA)-gene, respectively. Detection limits of the M-gene and the
      influenza A(H1N1)pdm09-specific HA-gene assays were 0.15 PFU and 8.8 PFU per
      reaction, respectively. With 18 influenza A viruses of different subtypes and
      influenza B, C, and 7 other respiratory viruses the RAZOR EX and standard real
      time PCR assay results were in total agreement. From 104 clinical samples
      identical results were obtained by both PCR methods. Additional 21 clinical
      samples were tested under field conditions with the RAZOR EX instrument. Results
      were achieved in 90 min, including 45 min for sample preparation and they were in
      complete agreement with those obtained by standard real-time PCR under laboratory
      conditions. These methods enable highly sensitive and rapid on-site diagnostics
      to reliably identify patients infected with influenza A, including the influenza
      A(H1N1)pdm09-virus.

PMID- 22374103
TI  - Typing of canine parvovirus isolates using mini-sequencing based single
      nucleotide polymorphism analysis.
AB  - The antigenic types of canine parvovirus (CPV) are defined based on differences
      in the amino acids of the major capsid protein VP2. Type specificity is conferred
      by a limited number of amino acid changes and in particular by few nucleotide
      substitutions. PCR based methods are not particularly suitable for typing
      circulating variants which differ in a few specific nucleotide substitutions.
      Assays for determining SNPs can detect efficiently nucleotide substitutions and
      can thus be adapted to identify CPV types. In the present study, CPV typing was
      performed by single nucleotide extension using the mini-sequencing technique. A
      mini-sequencing signature was established for all the four CPV types (CPV2, 2a,
      2b and 2c) and feline panleukopenia virus. The CPV typing using the mini
      sequencing reaction was performed for 13 CPV field isolates and the two vaccine
      strains available in our repository. All the isolates had been typed earlier by
      full-length sequencing of the VP2 gene. The typing results obtained from mini
      sequencing matched completely with that of sequencing. Typing could be achieved
      with less than 100 copies of standard plasmid DNA constructs or <=101 FAID50 of
      virus by mini-sequencing technique. The technique was also efficient for
      detecting multiple types in mixed infections.

PMID- 22374104
TI  - From ZnS nanoparticles, nanobelts, to nanotetrapods: the ethylenediamine
      modulated anisotropic growth of ZnS nanostructures.

PMID- 22374105
TI  - The Study Centre of the German Surgical Society: current trials and results.
AB  - PURPOSE: This article provides an overview of current and completed multicentre
      trials and systematic reviews performed by the Study Centre of the German
      Surgical Society (SDGC). BACKGROUND: The SDGC aims to transfer the concept of
      evidence-based medicine to surgery by planning, conducting and analyzing large
      national and international randomized multicentre trials concerning surgical
      issues. Every German surgeon may ask the SDGC for support to realize his clinical
      trial ideas. Another important task of the SDGC is the acquisition of trial
      funding from government institutions or industrial partners. DISCUSSION: Five
      multicentre randomized controlled trials (RCT) and 11 systematic reviews with
      meta-analyses have already been completed and published by the SDGC. Another
      seven RCTs are currently in the recruitment or follow up phase. A total of 2,500
      patients in over 100 trial centres have participated so far.

PMID- 22374107
TI  - Who uses anal sex for birth control?

PMID- 22374106
TI  - Cysto-biliary communication in liver hydatidosis.
AB  - BACKGROUND: Liver hydatidosis is a severe health problem in endemic areas. Due to
      migration from these countries to other zones, now it is a worldwide problem.
      Liver hydatidosis can provoke many complications (abscess, fistula to adjacent
      organs, migration, etc.), but the most frequent and one of the most severe
      complication is the communication between the cyst and the biliary tree. AIM: The
      aim of this study is to perform a review on the epidemiology, clinical features,
      diagnostic methods, and therapeutic options to treat the communication between
      the cyst and the biliary tree. RESULTS: Due to the lack of randomized clinical
      trial or meta-analysis on this topic, we performed a classical review and
      included our personal algorithm. CONCLUSIONS: The communication between the cyst
      and the biliary tree varies from a small communication to a frank intrabiliary
      rupture. The percentage of patients with the communication between the cyst and
      the biliary tree is not well known because there is no accepted definition. The
      therapeutic options are multiple and related to the size of the communication,
      the location of the cyst, and the experience of the hepatobiliary surgeon. ERCP
      is now an important tool for the treatment of the communication between the cyst
      and the biliary tree.

PMID- 22374108
TI  - Rape among women and girls presenting at a gynecological emergency department,
      North Bengal Medical College, Darjeeling, India.

PMID- 22374109
TI  - Analysis of the IJCNN 2011 UTL challenge.
AB  - We organized a challenge in "Unsupervised and Transfer Learning": the UTL
      challenge (http://clopinet.com/ul). We made available large datasets from various
      application domains: handwriting recognition, image recognition, video
      processing, text processing, and ecology. The goal was to learn data
      representations that capture regularities of an input space for re-use across
      tasks. The representations were evaluated on supervised learning "target tasks"
      unknown to the participants. The first phase of the challenge was dedicated to
      "unsupervised transfer learning" (the competitors were given only unlabeled
      data). The second phase was dedicated to "cross-task transfer learning" (the
      competitors were provided with a limited amount of labeled data from "source
      tasks", distinct from the "target tasks"). The analysis indicates that learned
      data representations yield significantly better results than those obtained with
      original data or data preprocessed with standard normalizations and functional
      transforms.

PMID- 22374111
TI  - Communicating uncertainty in economic evaluations: verifying optimal strategies.
AB  - BACKGROUND: In cost-effectiveness analysis (CEA), it is common to compare a
      single, new intervention with 1 or more existing interventions representing
      current practice ignoring other, unrelated interventions. Sectoral CEAs, in
      contrast, take a perspective in which the costs and effectiveness of all possible
      interventions within a certain disease area or health care sector are compared to
      maximize health in a society given resource constraints. Stochastic league tables
      (SLT) have been developed to represent uncertainty in sectoral CEAs but have 2
      shortcomings: 1) the probabilities reflect inclusion of individual interventions
      and not strategies and 2) data on robustness are lacking. The authors developed
      an extension of SLT that addresses these shortcomings. METHODS: Analogous to
      nonprobabilistic MAXIMIN decision rules, the uncertainty of the performance of
      strategies in sectoral CEAs may be judged with respect to worst possible
      outcomes, in terms of health effects obtainable within a given budget. Therefore,
      the authors assessed robustness of strategies likely to be optimal by performing
      optimization separately on all samples and on samples yielding worse than
      expected health benefits. The approach was tested on 2 examples, 1 with
      independent and 1 with correlated cost and effect data. RESULTS: The method was
      applicable to the original SLT example and to a new example and provided clear
      and easily interpretable results. Identification of interventions with robust
      performance as well as the best performing strategies was straightforward.
      Furthermore, the robustness of strategies was assessed with a MAXIMIN decision
      rule. CONCLUSION: The SLT extension improves the comprehensibility and extends
      the usefulness of outcomes of SLT for decision makers. Its use is recommended
      whenever an SLT approach is considered.

PMID- 22374113
TI  - How can veterinarians base their medical decisions on the best available
      scientific evidence?
AB  - With the advent of a One World-One Health concept, veterinarians will play a
      central role, at the level of trading zones (such as the European Union),
      countries, food production farms, and individual animals. They will be mandated
      to produce, interpret, communicate, and apply scientific information in the best
      possible way to make informed decisions and take adequate actions. The principles
      of evidence-based medicine will help the accomplishment of this mission. However,
      for the moment, we may still have the impression of two separate worlds, the
      academic research on one side and the reality of practice on the other side, and
      there is a need to join them.

PMID- 22374112
TI  - Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: The ability of the ImmuKnow (Cylex) assay to predict the risk of
      infection in rheumatoid arthritis (RA) patients receiving synthetic or biological
      disease-modifying antirheumatic drugs (DMARDs) was examined. METHODS: The amount
      of adenosine triphosphate (ATP) produced by CD4+ cells in response to
      phytohemagglutinin was measured in whole blood from 117 RA patients without
      infection versus 17 RA patients with infection, and compared with results in 75
      healthy controls. RESULTS: The mean ATP level was significantly lower in patients
      with infection compared to both healthy controls (P < 0.0005) and patients
      without infection (P = 0.040). Also, the mean ATP level in patients without
      infection was significantly lower than that in healthy controls (P = 0.012).
      There was no correlation between the ATP level and the Disease Activity Score in
      28 joints. CONCLUSION: ImmuKnow assay results may be effective in identifying RA
      patients at increased risk of infection, but the results showed no correlation
      with RA activity. Larger studies are required to establish the clinical
      advantages of this assay in RA treatment.

PMID- 22374114
TI  - Using systematic reviews to critically appraise the scientific information for
      the bovine veterinarian.
AB  - Bovine veterinarians need to base their clinical decisions on the best scientific
      evidence. Due to lack of time, the relevant information should be available in a
      structured and summarized publication, such as systematic reviews. The results
      and the discussion should be reported in a practical and useful way. A structured
      abstract helps the busy practitioner to have a quick look on the evidence gained
      by this approach. There is a lack of studies in many areas of ruminant health
      compared with human health. Although this can be perceived as a limitation,
      veterinarians and scientists should design strategies to develop more systematic
      reviews.

PMID- 22374115
TI  - Evidence related to the use of ancillary drugs in bovine respiratory disease
      (anti-inflammatory and others): are they justified or not?
AB  - The therapeutic approach for bovine respiratory disease (BRD) includes
      antimicrobial treatment due to the frequent implication of bacteria. The data
      concerning the use of ancillary drugs (such as anti-inflammatory drugs or
      immunomodulators) are scant and often are based on experimental models of BRD.
      The effect of NSAIDs on pulmonary lesions, despite appearing beneficial, remains
      to be confirmed in well-designed, long-term trials. The impact on weight gain is
      inconsistent in these studies. This review emphasized the need for articles
      concerning clinical trials to clearly state study inclusion criteria, and
      definitions of clinical scores, relapses, and treatment failures to be properly
      evaluated.

PMID- 22374116
TI  - Systematic review: what is the best antibiotic treatment for Staphylococcus
      aureus intramammary infection of lactating cows in North America?
AB  - Staphylococcus aureus is the most prevalent pathogen causing intramammary
      infections (IMI) in dairy cattle worldwide. New treatment regimens have been
      evaluated to increase cure rates. A systematic review was conducted to answer
      this question: what is the best antibiotic treatment for S aureus IMI of
      lactating cows in North America? Direct comparison between studies (n = 6) was
      difficult since there was no clinical trial comparing all antibiotics and large
      variations between study protocols and enrolment and outcome definitions were
      observed. The best therapeutic option currently available in North America is an
      extended intramammary therapy for 5 to 8 days.

PMID- 22374117
TI  - Evidence-based use of prokinetic drugs for abomasal disorders in cattle.
AB  - Abomasal hypomotility is a prerequisite for abomasal displacement in cattle and
      is present immediately after surgical correction of left displaced abomasum or
      abomasal volvulus. Hypocalcemia, hypokalemia, and hyperinsulinemia should be
      corrected in cattle suspected to have abomasal hypomotility. The most effective
      prokinetic for calves and adult cattle suspected to have abomasal hypomotility is
      erythromycin.

PMID- 22374118
TI  - Evidence-based medicine concerning efficacy of vaccination against Clostridium
      chauvoei infection in cattle.
AB  - Clostridium chauvoei infections occur frequently in cattle and produce disease
      end lethality. Vaccination is frequently used to prevent occurrence of these
      infections. Although the literature on blackleg is voluminous, scientific
      evidence on the efficacy of vaccination against C chauvoei to prevent diseases
      and lethality in cattle is scant. This study demonstrates that the evidence of
      efficacy of C chauvoei vaccines to prevent infection by this microorganism in
      cattle is poor to moderate. A greater participation of practitioners in clinical
      research and greater access to informational tools such as systematic reviews
      must be part of the objectives of veterinary medicine.

PMID- 22374119
TI  - Therapeutic efficiency of antibiotics and prostaglandin F2alpha in postpartum
      dairy cows with clinical endometritis: an evidence-based evaluation.
AB  - The occurrence of vaginal discharge in postpartum dairy cows is generally
      diagnosed as clinical endometritis. This uterine condition is associated with
      reduced fertility and economic loss for the dairy industry. Therapeutic
      approaches include the systemic or intrauterine application of antibiotics or the
      injection of prostaglandin F2alpha and analogues to cause luteolysis and uterine
      contractions to evacuate the infected content. The treatment of clinical
      endometritis remains a subject of considerable controversy in the literature.
      Better understanding of the reproductive biology of normal versus abnormal
      uterine involution and immune mechanisms will allow more efficient diagnostic
      methods and a more efficient therapeutic approach.

PMID- 22374120
TI  - Evidence-based effectiveness of vaccination against Mannheimia haemolytica,
      Pasteurella multocida, and Histophilus somni in feedlot cattle for mitigating the
      incidence and effect of bovine respiratory disease complex.
AB  - Bovine respiratory disease complex is the leading cause of morbidity and
      mortality in feedlot cattle. A number of vaccines against bacterial respiratory
      pathogens are commercially available and researchers have studied their impact on
      morbidity, mortality, and other disease outcome measures in feedlot cattle. A
      systematic review will provide veterinarians with a rigorous and transparent
      evaluation of the published literature to estimate the extent of vaccine effect.
      Unfortunately, the published body of evidence does not provide a consistent
      estimate of the direction and magnitude of effectiveness in feedlot cattle
      vaccination against Mannheimia haemolytica, Pasteurella multocida, or Histophilus
      somni.

PMID- 22374121
TI  - Overview of meta-analysis of monensin in dairy cattle.
AB  - Monensin is an ionophore widely used in the dairy cattle industry throughout the
      world. A large volume of clinical trials have been conducted that have explored
      efficacy for various metabolic, production, and health outcomes. However, the
      results of the individual studies have in some cases been contradictory and in
      others inadequately sized to fully address the objectives particularly for health
      and production. The meta-analysis of monensin dairy data illustrates an example
      of the power of this tool for helping to make evidence-based decisions for health
      management and production consultants. Its importance and utility will continue
      to grow in future years.

PMID- 22374122
TI  - Evidence-based early clinical detection of emerging diseases in food animals and
      zoonoses: two cases.
AB  - If diseases of food-producing animals or zoonoses (re-)emerge, early clinical
      decision making is of major importance. In this particular condition, it is
      difficult to apply a classic evidence-based veterinary medicine process, because
      of a lack of available published data. A method based on the partition of field
      clinical observations (evidences) could be developed as an interesting
      alternative approach. The classification and regression tree (CART) analysis was
      used to improve the early clinical detection in two cases of emerging diseases:
      bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the
      serotype 8-virus in cattle.

PMID- 22374123
TI  - Evidence-based practice? An evolution is necessary for bovine practitioners,
      teachers, and researchers.
AB  - We suggest a definition of evidence-based veterinary medicine that takes into
      account its objectives and practicality. We view it as an information tool that
      does not replace experience but helps to improve background knowledge and solve
      clinical foreground questions. It could be defined as the use of accurate,
      informative, and clear summarized information (abstracts) of high-level research
      studies that is obtained quickly via free-access databases available via the
      Internet and that is provided by a proactive veterinary scientific community in
      search of transparency, accountability, and evidence.

PMID- 22374124
TI  - Evidence-based veterinary medicine.

PMID- 22374126
TI  - Chelation-controlled molecular morphology: aminal to imine rearrangements.
AB  - Reactions between the tripodal hydroxytriamine, 2,2-bis(aminomethyl)-3
      aminopropan-1-ol, "hytame", and the isomeric pyridine aldehydes generate in all
      cases the tris(aminal) species based on a 1,3,5-triaza-adamantane skeleton. In
      all cases also, the product from water under basic conditions consists of an
      approximately 1:9 mixture of the triequatorial and monoaxial-diequatorial
      isomers. While all these tripyridyltriaza-adamantanes appear capable of acting as
      Lewis bases, in particular cases metal ion binding leads to a radical structural
      rearrangement. These cases involve the pyridine-2-aldehyde derivatives only and
      certain transition metal ions (notably Fe(II)), and result in the conversion of
      the tris(aminal) into its isomeric tris(imine) form. This is apparently favoured
      because it can act as a hexadentate ligand towards a single metal ion, although
      kinetic influences are clearly important in this chemistry because template
      reactions of the triamine, pyridine-2-aldehyde and several metal ions give much
      better yields of the tris(imine) complex than do analogous rearrangement
      reactions. For the low-spin, kinetically inert Fe(II) complex of the tris(imine),
      its formation is apparently so favourable that it is generated via aldehyde unit
      exchange when the aza-adamantanes derived from pyridine-3- and -4-aldehyde are
      heated with a mixture of Fe(II) and pyridine-2-aldehyde. When the kinetically
      labile Zn(II) complex is treated with EDTA, the metal ion is extracted but the
      released ligand does not undergo valence tautomerisation to what would be
      expected to be the triaxial isomer of the tripyridyltriaza-adamantane but instead
      rapidly undergoes partial hydrolysis before slowly forming the mixture of
      triequatorial and monoaxial-diequatorial isomers.

PMID- 22374125
TI  - The evolutionary origin of the vasopressin/V2-type receptor/aquaporin axis and
      the urine-concentrating mechanism.
AB  - In this mini-review, current evidence for how the vasopressin/V2-type
      receptor/aquaporin axis developed co-evolutionary as a crucial part of the urine
      concentrating mechanism will be presented. The present-day human kidney, allowing
      the concentration of urine up to a maximal osmolality around 1200 mosmol kg(-1)
      or urine to plasma osmolality ratio around 4-with essentially no sodium secreted
      is the result of up to 3 billion years evolution. Moving from aquatic to
      terrestrial habitats required profound changes in kidney morphology, most notable
      the loops of Henle modifying the kidneys from basically a water excretory system
      to a water conserving system. Vasopressin-like molecules has during the evolution
      played a significant role in body fluid homeostasis, more specifically, the
      osmolality of body liquids by controlling the elimination/reabsorption of fluid
      trough stimulating V2-type receptors to mobilize aquaporin water channels in the
      renal collector tubules. Recent evidence supports that all components of the
      vasopressin/V2-type receptor/aquaporin axis can be traced back to early
      precursors in evolutionary history. The potential clinical and pharmacological
      implications of a better phylogenetic understanding of these biological systems
      so essential for body fluid homeostasis relates to any pathological aspects of
      the urine-concentrating mechanism, in particular deficiencies of any part of the
      vasopressin-V2R-AQP2 axis causing central or nephrogenic diabetes insipidus-and
      for broader patient populations also in preventing and treating disturbances in
      human circadian regulation of urine volume and osmolality that may lead to
      enuresis and nocturia.

PMID- 22374127
TI  - Mitochondrial and nuclear DNA analysis revealed a cryptic species and genetic
      introgression in Littorina sitkana (Mollusca, Gastropoda).
AB  - We investigated mitochondrial and nuclear DNA genotypes in nominal Littorina
      sitkana samples from 2 localities in Eastern Hokkaido, northern Japan. Our
      results indicated the existence of cryptic species. In the analysis of partial
      mitochondrial Cytchrome b gene sequences, haplotypes of L. sitkana samples were
      monophyletic in a phylogenetic tree with orthologous sequences from other
      Littorina species, but were apparently separated in 2 clades. One included
      typical L. sitkana (CBa clade) samples, which formed a clade with an allopatric
      species, L. horikawai. The other, CBb, was independent from CBa and L. horikawai.
      Haplotypes of the mitochondrial 16S rRNA gene also separated into 2 clades. We
      additionally examined intron sequence of the heat shock cognate 70 (HSC70)
      nuclear gene and identified 17 haplotypes. These were also separated into 2
      clades, HSCa and HSCb. Among the examined Hokkaido samples, 60% of individuals
      were heterozygotes. However, each heterozygote consisted of haplotypes from the
      same clade, HSCa or HSCb, and no admixture of HSCa and HSCb haplotypes was
      observed. These results indicate reproductive isolation between the 2 clades.
      Among the genotyped Hokkaido samples, 93% of individuals had CBa + HSCa or CBb +
      HSCb genotypes, and 7% had CBb + HSCa genotypes. The discrepancy between the
      mtDNA and nuclear DNA haplotypes in a few individuals may have been caused by
      genetic introgression due to past hybridization.

PMID- 22374128
TI  - A novel non-synonymous mutation in the homeodomain of HOXD13 causes
      synpolydactyly in a Chinese family.
AB  - PURPOSE: The 5' HoxD genes and their paralogs in the HoxD cluster are crucial for
      normal vertebrate limb development. Mutations in HOXD13 and HOXD13 have been
      found to cause human limb malformation. Here we describe a two-generation Chinese
      family with a variant form of mild synpolydactyly. METHODS: Sequence analysis of
      HOXD13 gene in a two-generation Chinese family with six individuals. RESULTS:
      Gene scan and linkage analysis suggested that HOXD13 might be responsible for the
      disease of this family. An LOD around 1.8 was observed at three markers (P=2E(
      3)). We identified a novel c.893G>A (p.Arg298Gln) mutation in the HOXD13
      homeodomain. And the mutation affected the transcriptional activation ability of
      HOXD13. CONCLUSION: This finding expands the phenotypic spectrum associated with
      HOXD13 mutations and advances our understanding of human limb development.

PMID- 22374129
TI  - Brain-derived neurotrophic factor not associated with metabolic syndrome but
      inversely correlated with vascular cell adhesion molecule-1 in men without
      diabetes.
AB  - BACKGROUND: Excessive visceral fat with unbalanced adipokines is a critical
      pathogenic factor of metabolic syndrome (MetS), which is associated with
      disorders of the central nervous system and cardiovascular disease. Because brain
      derived neurotrophic factor (BDNF) plays an important role in neurons, we
      examined the relationship of BDNF to MetS, adipose tissue and biomarkers in men.
      METHODS: Thirty-four non-diabetic men with MetS and another 24 age-matched men
      without MetS were enrolled. In addition to fasting blood samples, the area of
      adipose tissue at the waist was assessed by magnetic resonance imaging (MRI).
      RESULTS: There was no significant difference in serum BDNF concentrations between
      men with or without MetS (40.9+/-8.0 vs. 43.2+/-6.1 ng/ml, P=0.235). However, the
      serum concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) was
      higher in the subjects with a lower BDNF level (737+/-230 vs. 628+/-115 ng/ml,
      P=0.025). An inverse correlation between VCAM-1 and BDNF was observed (r=-0.391,
      P=0.002). After adjusting for visceral adipose tissue, VCAM-1 was found to be
      independently associated with BDNF [95% confidence interval (-0.025, -0.005),
      P=0.004]. CONCLUSION: These data show no difference in serum BDNF levels between
      the men with MetS and controls. However, serum BDNF was inversely correlated with
      serum VCAM-1 in men without diabetes.

PMID- 22374130
TI  - Invasive interventional management of post-hemorrhagic cerebral vasospasm in
      patients with aneurysmal subarachnoid hemorrhage.
AB  - Current clinical practice standards are addressed for the invasive interventional
      management of post-hemorrhagic cerebral vasospasm (PHCV) in patients with
      aneurysmal subarachnoid hemorrhage. The conclusions, based on an assessment by
      the Standards Committee of the Society of Neurointerventional Surgery, included a
      critical review of the literature using guidelines for evidence based medicine
      proposed by the Stroke Council of the American Heart Association and the
      University of Oxford, Centre for Evidence Based Medicine. Specifically examined
      were the safety and efficacy of established invasive interventional therapies,
      including transluminal balloon angioplasty (TBA) and intra-arterial vasodilator
      infusion therapy (IAVT). The assessment shows that these invasive interventional
      therapies may be beneficial and may be considered for PHCV-that is, symptomatic
      with cerebral ischemia and refractory to maximal medical management. As outlined
      in this document, IAVT may be beneficial for the management of PHCV involving the
      proximal and/or distal intradural cerebral circulation. TBA may be beneficial for
      the management of PHCV that involves the proximal intradural cerebral
      circulation. The assessment shows that for the indications described above, TBA
      and IAVT are classified as Class IIb, Level B interventions according to the
      American Heart Association guidelines, and Level 4, Grade C interventions
      according to the University of Oxford Centre for Evidence Based Medicine
      guidelines.

PMID- 22374131
TI  - A carving method to determine an optimal working projection using three
      dimensional volume rendering digital subtraction angiography in coil embolization
      of cerebral aneurysms.
AB  - BACKGROUND: A working projection in coil embolization of a cerebral aneurysm is
      usually determined using three-dimensional volume rendering digital subtraction
      angiography (3D VRDSA), in which the boundary between an aneurysm and its parent
      artery cannot be identified simultaneously on the front and back surfaces of the
      vessel. A new method was devised to obtain a more optimal working projection.
      METHODS: 83 patients with aneurysms being treated by embolization were
      retrospectively evaluated. An aneurysm was accurately distinguished from the
      parent artery by observation of front, back, proximal and distal sides of the
      vessel on 3D VRDSA (carving method). An optimal working projection with
      simultaneous identification of the front and back boundary lines was determined
      using a translucent vessel complex combined with the carved aneurysm. RESULTS: In
      32 aneurysms (38.6%), the optimal working projection was consistent with the
      working projection that had been used during the procedure. In terminal type
      aneurysms, the angle difference between the optimal and actual working
      projections was significantly smaller than in the other types (p<0.05). Aneurysms
      with a maximal diameter <5 mm showed a significantly larger angle difference
      between the optimal and actual working projections than aneurysms with a maximal
      diameter >=5 mm (p<0.05). CONCLUSION: In more than half of the patients, the
      actual working projection was inaccurate. The carving method might be useful to
      determine working projections, especially for aneurysms other than the terminal
      type and/or those with a maximal diameter <5 mm.

PMID- 22374132
TI  - A human 3' miR-499 mutation alters cardiac mRNA targeting and function.
AB  - RATIONALE: MyomiRs miR-499, miR-208a and miR-208b direct cardiac myosin gene
      expression. Sequence complementarity between miRs and their mRNA targets
      determines miR effects, but the functional consequences of human myomiR sequence
      variants are unknown. OBJECTIVE: To identify and investigate mutations in human
      myomiRs in order to better understand how and to what extent naturally-occurring
      sequence variation can impact miR-mRNA targeting and end-organ function. METHODS
      AND RESULTS: Screening of ~2,600 individual DNAs for myomiR sequence variants
      identified a rare mutation of miR-499, u17c in the 3' end, well outside the seed
      region thought to determine target recognition. In vitro luciferase reporter
      analysis showed that the 3' miR-499 mutation altered suppression of a subset of
      artificial and natural mRNA targets. Cardiac-specific transgenic expression was
      used to compare consequences of wild-type and mutant miR-499. Both wild-type and
      mutant miR-499 induced heart failure in mice, but miR-499 c17 misdirected
      recruitment of a subset of miR-499 target mRNAs to cardiomyocyte RNA-induced
      silencing complexes, altering steady-state cardiac mRNA and protein make-up and
      favorably impacting cardiac function. In vitro analysis of miR-499 target site
      mutations and modeling of binding energies revealed abnormal miR-mRNA duplex
      configurations induced by the c17 mutation. CONCLUSIONS: A naturally occurring
      miR-499 mutation outside the critical seed sequence modifies mRNA targeting and
      end-organ function. This first description of in vivo effects from a natural
      human miR mutation outside the seed sequence supports comprehensive studies of
      individual phenotypes or disease-modification conferred by miR mutations.

PMID- 22374133
TI  - Novel genetic approach for in vivo vascular imaging in mice.
AB  - RATIONALE: The formation and maintenance of a functional vasculature is essential
      for normal embryonic development, and genetic changes that affect the vasculature
      underlie pathogenesis in many human diseases. In vivo imaging in mouse models is
      required to understand the full complexity of mammalian vascular formation, which
      is a dynamic and 3-dimensional process. Optical microscopy of genetically
      expressed fluorescent reporter proteins offers high resolution but limited depth
      of penetration in vivo. Conversely, there are a plethora of molecular probes for
      alternative in vivo vascular imaging modalities, but few options for genetic
      control of contrast enhancement. OBJECTIVE: To develop a reporter system for
      multimodal imaging of genetic processes involved in mammalian vascular biology.
      METHODS AND RESULTS: To approach this problem, we developed an optimal tagging
      system based on Biotag-BirA technology. In the resulting Biotag reporter system,
      coexpression of 2 interacting proteins results in biotin labeling of cell
      membranes, thus enabling multimodal imaging with "avidinated" probes. To assess
      this approach for in vivo imaging, we generated transgenic mice that expressed
      the Biotag-BirA transgene from a minimal Tie2 promoter. A variety of imaging
      methods were used to show the utility of this approach for quantitative analysis
      in embryonic and adult models of vascular development, using intravascular
      injection of avidinated probes for near infrared, ultrasound, and magnetic
      resonance imaging. CONCLUSIONS: The present results demonstrate the versatility
      of the Biotag system for studies of vascular biology in genetically engineered
      mice, providing a robust approach for multimodal in vivo imaging of genetic
      processes in the vasculature.

PMID- 22374134
TI  - Abnormal termination of Ca2+ release is a common defect of RyR2 mutations
      associated with cardiomyopathies.
AB  - RATIONALE: Naturally occurring mutations in the cardiac ryanodine receptor (RyR2)
      have been associated with both cardiac arrhythmias and cardiomyopathies. It is
      clear that delayed afterdepolarization resulting from abnormal activation of
      sarcoplasmic reticulum Ca2+ release is the primary cause of RyR2-associated
      cardiac arrhythmias. However, the mechanism underlying RyR2-associated
      cardiomyopathies is completely unknown. OBJECTIVE: In the present study, we
      investigate the role of the NH2-terminal region of RyR2 in and the impact of a
      number of cardiomyopathy-associated RyR2 mutations on the termination of Ca2+
      release. METHODS AND RESULTS: The 35-residue exon-3 region of RyR2 is associated
      with dilated cardiomyopathy. Single-cell luminal Ca2+ imaging revealed that the
      deletion of the first 305 NH2-terminal residues encompassing exon-3 or the
      deletion of exon-3 itself markedly reduced the luminal Ca2+ threshold at which
      Ca2+ release terminates and increased the fractional Ca2+ release. Single-cell
      cytosolic Ca2+ imaging also showed that both RyR2 deletions enhanced the
      amplitude of store overload-induced Ca2+ transients in HEK293 cells or HL-1
      cardiac cells. Furthermore, the RyR2 NH2-terminal mutations, A77V, R176Q/T2504M,
      R420W, and L433P, which are associated with arrhythmogenic right ventricular
      displasia type 2, also reduced the threshold for Ca2+ release termination and
      increased fractional release. The RyR2 A1107M mutation associated with
      hypertrophic cardiomyopathy had the opposite action (i.e., increased the
      threshold for Ca2+ release termination and reduced fractional release).
      CONCLUSIONS: These results provide the first evidence that the NH2-terminal
      region of RyR2 is an important determinant of Ca2+ release termination, and that
      abnormal fractional Ca2+ release attributable to aberrant termination of Ca2+
      release is a common defect in RyR2-associated cardiomyopathies.

PMID- 22374135
TI  - Regulation of cell cycle transcription factor Swi5 by karyopherin Msn5.
AB  - Inactivation of S. cerevisiae beta-karyopherin Msn5 causes hypersensitivity to
      the overexpression of mitotic cyclin Clb2 and aggravates growth defects of many
      mutant strains in mitotic exit, suggesting a connection between Msn5 and mitotic
      exit. We determined that Msn5 controlled subcellular localization of the mitotic
      exit transcription factor Swi5, since it was required for Swi5 nuclear export.
      Msn5 physically interacted with the N-terminal end of Swi5. Inactivation of Msn5
      caused a severe reduction in cellular levels of Swi5 protein. This effect
      occurred by a post-transcriptional mechanism, since SWI5 mRNA levels were not
      affected. The reduced amount of Swi5 in msn5 mutant cells was not due to an
      increased protein degradation rate, but to a defect in Swi5 synthesis. Despite
      the change in localization and protein level, Swi5-regulated transcription was
      not defective in the msn5 mutant strain. However, a high level of Swi5 was toxic
      in the absence of Msn5. This deleterious effect was eliminated when Swi5 nuclear
      import was abrogated, suggesting that nuclear export by Msn5 is important for
      cell physiology, because it prevents toxic Swi5 nuclear accumulation.

PMID- 22374137
TI  - Amino acid ionic liquid-based facilitated transport membranes for CO2 separation.
AB  - Supported liquid membranes incorporating amino acid ionic liquids remarkably
      facilitate CO(2) permeation under dry and low humid conditions.

PMID- 22374138
TI  - Identification of a new soybean rust resistance gene in PI 567102B.
AB  - Soybean rust (SBR) caused by Phakopsora pachyrhizi Syd. and P. Syd. is one of the
      most economically important diseases of soybean (Glycine max (L.) Merr.). Durable
      resistance to P. pachyrhizi is the most effective long-term strategy to control
      SBR. The objective of this study was to investigate the genetics of resistance to
      P. pachyrhizi in soybean accession PI 567102B. This accession was previously
      identified as resistant to SBR in Paraguay and to P. pachyrhizi isolates from
      seven states in the USA (Alabama, Florida, Georgia, Louisiana, Mississippi, South
      Carolina, and Texas). Analysis of two independent populations, one in which F(2)
      phenotypes were inferred from F(2)-derived F(3) (F(2:3)) families and the other
      in which F(2) plants had phenotypes measured directly, showed that the resistance
      in PI 567102B was controlled by a single dominant gene. Two different isolates
      (MS06-1 and LA04-1) at different locations (Stoneville, MS and Ft. Detrick, MD)
      were used to independently assay the two populations. Linkage analysis of both
      populations indicated that the resistance locus was located on chromosome 18
      (formerly linkage group G), but at a different location than either Rpp1 or Rpp4,
      which were previously mapped to this linkage group. Therefore, the SBR resistance
      in PI 567102B appeared to be conditioned by a previously unreported locus, with
      an underlying single dominant gene inferred. We propose this gene to be
      designated Rpp6. Incorporating Rpp6 into improved soybean cultivars may have wide
      benefits as PI 567102B has been shown to provide resistance to P. pachyrhizi
      isolates from Paraguay and the US.

PMID- 22374136
TI  - The retrograde response: when mitochondrial quality control is not enough.
AB  - Mitochondria are responsible for generating adenosine triphosphate (ATP) and
      metabolic intermediates for biosynthesis. These dual functions require the
      activity of the electron transport chain in the mitochondrial inner membrane. The
      performance of these electron carriers is imperfect, resulting in release of
      damaging reactive oxygen species. Thus, continued mitochondrial activity requires
      maintenance. There are numerous means by which this quality control is ensured.
      Autophagy and selective mitophagy are among them. However, the cell inevitably
      must compensate for declining quality control by activating a variety of
      adaptations that entail the signaling of the presence of mitochondrial
      dysfunction to the nucleus. The best known of these is the retrograde response.
      This signaling pathway is triggered by the loss of mitochondrial membrane
      potential, which engages a series of signal transduction proteins, and it
      culminates in the induction of a broad array of nuclear target genes. One of the
      hallmarks of the retrograde response is its capacity to extend the replicative
      life span of the cell. The retrograde signaling pathway interacts with several
      other signaling pathways, such as target of rapamycin (TOR) and ceramide
      signaling. All of these pathways respond to stress, including metabolic stress.
      The retrograde response is also linked to both autophagy and mitophagy at the
      gene and protein activation levels. Another quality control mechanism involves
      age-asymmetry in the segregation of dysfunctional mitochondria. One of the
      processes that impinge on this age-asymmetry is related to biogenesis of the
      organelle. Altogether, it is apparent that mitochondrial quality control
      constitutes a complex network of processes, whose full understanding will require
      a systems approach. This article is part of a Special Issue entitled: Protein
      Import and Quality Control in Mitochondria and Plastids.

PMID- 22374139
TI  - Genetic dissection of grain yield and physical grain quality in bread wheat
      (Triticum aestivum L.) under water-limited environments.
AB  - In the water-limited bread wheat production environment of southern Australia,
      large advances in grain yield have previously been achieved through the
      introduction and improved understanding of agronomic traits controlled by major
      genes, such as the semi-dwarf plant stature and photoperiod insensitivity.
      However, more recent yield increases have been achieved through incremental
      genetic advances, of which, breeders and researchers do not fully understand the
      underlying mechanism(s). A doubled haploid population was utilised, derived from
      a cross between RAC875, a relatively drought-tolerant breeders' line and Kukri, a
      locally adapted variety more intolerant of drought. Experiments were performed in
      16 environments over four seasons in southern Australia, to physiologically
      dissect grain yield and to detect quantitative trait loci (QTL) for these traits.
      Two stage multi-environment trial analysis identified three main clusters of
      experiments (forming distinctive environments, ENVs), each with a distinctive
      growing season rainfall patterns. Kernels per square metre were positively
      correlated with grain yield and influenced by kernels per spikelet, a measure of
      fertility. QTL analysis detected nine loci for grain yield across these ENVs,
      individually accounting for between 3 and 18% of genetic variance within their
      respective ENVs, with the RAC875 allele conferring increased grain yield at seven
      of these loci. These loci were partially dissected by the detection of co-located
      QTL for other traits, namely kernels per square metre. While most loci for grain
      yield have previously been reported, their deployment and effect within local
      germplasm are now better understood. A number of novel loci can be further
      exploited to aid breeders' efforts in improving grain yield in the southern
      Australian environment.

PMID- 22374141
TI  - Current world literature.

PMID- 22374140
TI  - Proresolving lipid mediators and diabetic wound healing.
AB  - PURPOSE OF REVIEW: Defective wound healing is one of the most prominent clinical
      manifestations of both type 1 and type 2 diabetes. As the global rates of
      diabetes increase, a detailed understanding of the molecular and cellular defects
      that give rise to unresolved inflammation and delayed wound healing in diabetes
      is urgently required. Emerging evidence indicates that timely resolution of
      inflammation is mediated in part by endogenous proresolving lipid mediators, such
      as resolvins. Here, we review recent advances in the area of resolution and
      diabetes and highlight the potential of novel proresolving strategies for
      promoting wound healing in diabetes. RECENT FINDINGS: Macrophage dysfunction is a
      critical underlying feature of altered wound healing in diabetic patients. This
      is associated with defective clearance of apoptotic cells, increased risk of
      infection, and altered angiogenesis. Diabetes and obesity are associated with
      chronic inflammation and altered biosynthesis of bioactive lipid mediators that
      promote the resolution of inflammation. Stimulating resolution with proresolving
      lipid mediators improves metabolic parameters in diabetes, blunts systemic
      inflammation, restores defective macrophage phagocytosis, and accelerates wound
      healing in animal models of obesity and diabetes. SUMMARY: Stimulating resolution
      with proresolving lipid mediators may represent a novel strategy for promoting
      wound healing in diabetes.

PMID- 22374143
TI  - Metabolism: Fat discovers a new ancestor.

PMID- 22374145
TI  - Sirtuins and calorie restriction.

PMID- 22374146
TI  - Technique: Lights on gene expression.

PMID- 22374148
TI  - Defining the coronary slow flow phenomenon.

PMID- 22374147
TI  - Missense mutations of the BMPR1B (ALK6) gene in childhood idiopathic pulmonary
      arterial hypertension.
AB  - BACKGROUND: Mutations in the bone morphogenetic protein receptor type 2 (BMPR2)
      gene, the activin receptor-like kinase 1 (ALK1) gene, and SMAD8 gene have been
      reported in heritable pulmonary arterial hypertension (HPAH) and in idiopathic
      pulmonary arterial hypertension (IPAH). However, almost 30% of HPAH cases and 60
      90% of IPAH cases have no mutations in those genes. This suggests that there
      remain unidentified genes associated with HPAH and IPAH. METHODS AND RESULTS:
      This study screened for mutations in endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5,
      SMAD6, SMAD7, bone morphogenetic protein receptor type 1A (BMPR1A) and bone
      morphogenetic protein receptor type 1B (BMPR1B) genes in 43 IPAH patients who had
      no mutations in BMPR2, ALK1 and SMAD8. Two missense mutations (c.479 G>A S160N,
      c.1176 C>A F392L) in BMPR1B were each identified in 2 IPAH patients. Immunoblot
      analysis revealed that the BMPR1B F392L protein promoted SMAD8 phosphorylation.
      The response to BMP was analyzed using promoter-reporter activities. The
      transcriptional activation of the BMPR1B F392L protein with SMAD8 increased above
      that of wild-type BMPR1B with SMAD8, and those of BMPR1B S160N and F392L with
      SMAD8 and SMAD4 were each increased above those of the wild-type BMPR1B with
      SMAD8 and SMAD4. CONCLUSIONS: We identified 2 novel mutations in BMPR1B in 2
      patients with IPAH. Our study suggests that BMPR1B mutations are associated with
      the pathogenesis of IPAH.

PMID- 22374149
TI  - Edge-to-edge percutaneous repair of severe mitral regurgitation--state-of-the-art
      for Mitraclip(r) implantation.
AB  - MitraClip(r) therapy is a percutaneous edge-to-edge plication of the mitral
      leaflets, mimicking the Alfieri surgical technique. MitraClip(r) implantation is
      a safe procedure, and survival outcomes in high-surgical-risk patients are
      superior to historical controls. Despite these results, questions remain
      concerning long-term efficacy and durability. The MitraClip(r) device has been
      studied in a safety and feasibility trial in the USA, a randomized pivotal trial
      against surgical mitral valve repair. Moreover, MitraClip(r) now has over 2 years
      of CE-mark approval and a rapidly expanding clinical experience in Europe,
      primarily in patients at high risk for surgery. A dedicated multidisciplinary
      team is necessary, as well as thoughtful patient selection, familiarity with the
      technical aspects of the procedure, including transesophageal ultrasound imaging
      and post-procedure monitoring. Currently available clinical data and procedural
      steps are herein reviewed. Because the MitraClip(r) procedure is still relatively
      new, continued investigation is required to further better define the patient
      populations that will benefit most.

PMID- 22374150
TI  - Clinical usefulness of cardiovascular magnetic resonance imaging in the diagnosis
      of takotsubo cardiomyopathy.

PMID- 22374151
TI  - Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.
AB  - PURPOSE: Clinical and epidemiologic investigations suggest a strong association
      between obesity and obstructive sleep apnea (OSA). The purpose of this study is
      to evaluate the currently available literature reporting on the effectiveness of
      dietary weight loss in treating OSA among obese patients. METHODS: Relevant
      studies were identified by computerized searches of PubMed, EMBASE, CINAHL, Web
      of Science, and The Cochrane Central Register of Controlled Trials through
      September 2011 as well as the reference lists of all obtained articles.
      Information on study design, patient characteristics, pre- and post-dietary
      weight loss measures of OSA and body mass index (BMI), and study quality was
      obtained. Data were extracted by two independent analysts. Weighted averages
      using a random-effects model are reported with 95 % confidence intervals.
      RESULTS: Nine articles representing 577 patients were selected. Dietary weight
      loss program resulted in a pooled mean BMI reduction of 4.8 kg/m(2) (95 %
      confidence interval [CI] 3.8-5.9). The random-effects pooled apnea hypopnea (AHI)
      indices at pre- and post-dietary intervention were 52.5 (range 10.0-91.0) and
      28.3 events/h (range 5.4-64.5), respectively (p < 0.001). Compared to control,
      the weighted mean difference of AHI was decreased by -14.3 events/h (95 % CI 
      23.5 to -5.1; p = 0.002) in favor of the dietary weight loss programs.
      CONCLUSIONS: Dietary weight loss programs are effective in reducing the severity
      of OSA but not adequate in relieving all respiratory events. Weight reduction
      programs should be considered as adjunct rather than curative therapy.

PMID- 22374152
TI  - Combustion behaviours of tobacco stem in a thermogravimetric analyser and a pilot
      scale fluidized bed reactor.
AB  - Despite its abundant supply, tobacco stem has not been exploited as an energy
      source in large scale. This study investigates the combustion behaviours of
      tobacco stem in a thermogravimetric analyser (TGA) and a pilot-scale fluidized
      bed (FB). Combustion characteristics, including ignition and burnout index, and
      combustion reaction kinetics were studied. Experiments in the FB investigated the
      effects of different operating conditions, such as primary air flow, secondary
      air flow and feeding rates, on the bed temperature profiles and combustion
      efficiency. Two kinds of bed materials cinder and silica sand were used in FB and
      the effect of bed materials on agglomeration was studied. The results indicated
      that tobacco stem combustion worked well in the FB. When operation condition was
      properly set, the tobacco stem combustion efficiency reached 94%. In addition,
      compared to silica sand, cinder could inhibit agglomeration during combustion
      because of its high aluminium content.

PMID- 22374153
TI  - Comparison of age-related macular degeneration treatment trials: what did we
      learn?

PMID- 22374154
TI  - Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with
      intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial
      growth factor Trap-eye).
AB  - PURPOSE: Monthly dosing with inhibitors of vascular endothelial growth factor
      (VEGF) results in stable or improved visual acuity in most patients with
      neovascular age-related macular degeneration. However, a minority of patients
      show little if any response to therapy with persistent or worsening macular
      fluid. Pharmacokinetic modeling was performed to determine if more frequent
      dosing with anti-VEGF drugs could be theoretically beneficial. METHODS: A
      mathematical model comparing the time-dependent relative binding activities of
      ranibizumab, bevacizumab, and aflibercept (VEGF Trap-eye; VTE) was used to
      determine the theoretical peak and trough binding activities when the drugs were
      injected every 14 days and every 28 days. The intravitreal half-lives of
      ranibizumab, bevacizumab, and the VTE were estimated to be 3.2, 5.6, and 4.8
      days, respectively. The relative molar binding activities of ranibizumab,
      bevacizumab, and the VTE used in the analyses were 1, 0.05 to 0.2, and 140,
      respectively. The expected peak and trough binding activities for ranibizumab,
      bevacizumab, and VTE were calculated. Dosing every 2 weeks was performed on
      selected patients who had a poor response to monthly therapy. RESULTS: Dosing of
      a drug every 2 weeks resulted in markedly improved trough binding activity, but
      had little impact on the peak binding activity when calculated through Day 28.
      The dosing of bevacizumab every 2 weeks resulted in trough binding levels that
      were superior to monthly dosing with ranibizumab at a dose of 0.5 mg and
      potentially superior to the levels achieved when ranibizumab was dosed monthly at
      a dose of 2.0 mg. The VTE displayed superior binding levels for both peak and
      trough levels even when compared with ranibizumab doses given every 2 weeks. Two
      case reports demonstrate the clinical usefulness of dosing with anti-VEGF therapy
      every 2 weeks in eyes with VEGF-dependent macular fluid appearing to be
      refractory to monthly dosing. CONCLUSION: The theoretical increase in trough
      binding levels when anti-VEGF drugs are dosed every 2 weeks most likely explains
      the clinical benefit observed in patients who received biweekly injections after
      their poor response to monthly therapy. The short-term use of biweekly dosing may
      be an attractive treatment option for those eyes that show a treatment response
      within 2 weeks of an injection, but rebound with increased macular fluid after a
      month. In the future, VTE should provide higher trough levels of anti-VEGF
      binding activity and eliminate the need for biweekly dosing in those eyes with
      VEGF-mediated exudation that appear unresponsive to monthly ranibizumab or
      bevacizumab.

PMID- 22374155
TI  - Reducing oral flora contamination of intravitreal injections with face mask or
      silence.
AB  - PURPOSE: To provide experimental evidence to support or refute the proposition
      that the use of surgical face masks and/or avoidance of talking can decrease the
      dispersion of respiratory flora during an intravitreal injection. METHODS: Ten
      surgeons recited a 30-second standardized script with blood agar plates
      positioned 30 cm below their mouths. The plates were divided into 4 groups, with
      10 plates per group. In Group 1, participants did not wear a face mask. In Group
      2, participants wore a standard surgical mask. In Group 3, no mask was worn, but
      plates were pretreated with 5% povidone-iodine. In Group 4, no mask was worn, and
      participants remained silent for 30 seconds. The plates were then incubated at 37
      degrees C for 24 hours, and the number of colony-forming units (CFUs) was
      determined. RESULTS: Mean bacterial growth were as follows: Group 1, 8.6 CFUs per
      subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group
      4, 2.4 CFUs per subject. Differences between the groups were statistically
      significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115).
      CONCLUSION: The use of a face mask and avoidance of talking each significantly
      decreased the dispersion of bacteria. Even without these interventions, plates
      pretreated with povidone-iodine demonstrated the least bacterial growth.

PMID- 22374156
TI  - Macular epiretinal membrane peeling treatment outcomes in young children.
AB  - PURPOSE: The purpose of this study was to describe macular epiretinal membrane
      (ERM) peeling treatment outcomes in young children. METHODS: The medical records
      of all vitrectomies from 1998 through 2010 were retrospectively reviewed.
      Patients who were selected were 16 years or younger and had primarily macular or
      posterior pole disease secondary to an ERM. Patients with retinopathy of
      prematurity, Coats disease, Norrie disease, and incontinentia pigmenti were
      excluded. Fourteen patients underwent vitrectomy with ERM peeling, and their
      preoperative and postoperative visual acuities were compared. RESULTS: The mean
      age at surgery was 8 years, with an average follow-up of 4.2 years (range, 6
      months to 11 years). The average presenting visual acuity was 20/258. Average
      postoperative visual acuity was 20/100, with improvement in 12 patients (86%) and
      no change of visual acuity in 2 patients (14%). CONCLUSION: Pediatric ERMs
      respond well to vitrectomy and membrane peel with a low likelihood of recurrence.
      Other associated pathology, such as familial exudative retinopathy and combined
      hamartomas of the retina and retinal pigment epithelium, was associated with
      complications, such as delayed-onset rhegmatogenous retinal detachment from
      peripheral traction and recurrence of ERM in 7% of patients.

PMID- 22374157
TI  - Choroidal thickness in patients with diabetic retinopathy analyzed by spectral
      domain optical coherence tomography.
AB  - PURPOSE: This study was designed to examine choroidal thickness in patients with
      diabetes using spectral-domain optical coherence tomography. METHODS: Forty-nine
      patients (49 eyes) with diabetes and 24 age-matched normal subjects underwent
      high-definition raster scanning using spectral-domain optical coherence
      tomography with frame enhancement software. Patients with diabetes were
      classified into 3 groups: 11 patients with mild or moderate nonproliferative
      diabetic retinopathy and no macular edema, 18 patients with nonproliferative
      diabetic retinopathy and diabetic macular edema, and 20 patients with treated
      proliferative diabetic retinopathy and no diabetic macular edema (treated
      proliferative diabetic retinopathy). Choroidal thickness was measured from the
      posterior edge of the retinal pigment epithelium to the choroid/sclera junction
      at 500-MUm intervals up to 2,500 MUm temporal and nasal to the fovea. RESULTS:
      Reliable measurements of choroidal thickness were obtainable in 75.3% of eyes
      examined. Mean choroidal thickness showed a pattern of thinnest choroid nasally,
      thickening in the subfoveal region, and thinning again temporally in normal
      subjects and patients with diabetes. Mean subfoveal choroidal thickness was
      thinner in patients with diabetic macular edema (63.3 MUm, 27.2%, P < 0.05) or
      treated proliferative diabetic retinopathy (69.6 MUm, 30.0%, P < 0.01), compared
      with normal subjects. There was no difference between nonproliferative diabetic
      retinopathy and normal subjects. CONCLUSION: Choroidal thickness is altered in
      diabetes and may be related to the severity of retinopathy. Presence of diabetic
      macular edema is associated with a significant decrease in the choroidal
      thickness.

PMID- 22374158
TI  - Proportional reflux hydrodissection.

PMID- 22374159
TI  - Foveola nonpeeling technique in internal limiting membrane peeling of myopic
      foveoschisis surgery.

PMID- 22374160
TI  - Diagnostic and therapeutic challenges.

PMID- 22374161
TI  - New miniaturized contact lens for wide-angle fundus fluorescein angiography: wide
      angle fluorescein angiography lens.

PMID- 22374162
TI  - High-resolution Fourier-domain optical coherence tomography findings in
      subretinal cysticercosis.

PMID- 22374163
TI  - Pathogenesis of rhegmatogenous retinal detachment, predisposing anatomy and cell
      biology.

PMID- 22374165
TI  - The zinc finger protein ZBTB20 regulates transcription of fructose-1,6
      bisphosphatase 1 and beta cell function in mice.
AB  - BACKGROUND & AIMS: Fructose-1,6-bisphosphatase (FBP)-1 is a gluconeogenic enzyme
      that regulates glucose metabolism and insulin secretion in beta cells, but little
      is known about how its transcription is controlled. The zinc finger protein
      ZBTB20 regulates glucose homeostasis, so we investigated its effects on
      expression of FBP-1. METHODS: We analyzed gene expression using real-time reverse
      transcription polymerase chain reaction, immunoblotting, and
      immunohistochemistry. We generated mice with beta cell-specific disruption of
      Zbtb20 using Cre/LoxP technology. Expression of Zbtb20 in beta cells was reduced
      using small interfering RNAs, and promoter occupancy and transcriptional
      regulation were analyzed by chromatin immunoprecipitation and reporter assays.
      RESULTS: ZBTB20 was expressed at high levels by beta cells and other endocrine
      cells in islets of normal mice; expression levels were reduced in islets from
      diabetic db/db mice. Mice with beta cell-specific knockout of Zbtb20 had normal
      development of beta cells but had hyperglycemia, hypoinsulinemia, glucose
      intolerance, and impaired glucose-stimulated insulin secretion. Islets isolated
      from these mice had impaired glucose metabolism, adenosine triphosphate
      production, and insulin secretion after glucose stimulation in vitro, although
      insulin secretion returned to normal levels in the presence of KCl. ZBTB20
      knockdown with small interfering RNAs impaired glucose-stimulated insulin
      secretion in the beta cell line MIN6. Expression of Fbp1 was up-regulated in beta
      cells with ZBTB20 knockout or knockdown; impairments to glucose-stimulated
      insulin secretion were restored by inhibition of FBPase activity. ZBTB20 was
      recruited to the Fbp1 promoter and repressed its transcription in beta cells.
      CONCLUSIONS: The transcription factor ZBTB20 regulates beta cell function and
      glucose homeostasis in mice. It might be a therapeutic target for type 2 diabetes
      mellitus.

PMID- 22374166
TI  - The zinc transporter Zip14 influences c-Met phosphorylation and hepatocyte
      proliferation during liver regeneration in mice.
AB  - BACKGROUND & AIMS: Zinc homeostasis in cells is maintained through tight
      regulation of zinc influx, efflux, and distribution to intracellular organelles
      by zinc transporters. The Zrt-Irt-like protein (ZIP) transporters facilitate zinc
      influx to the cytosol. Expression of the ZIP family member Zip14 can be induced
      by inflammatory cytokines, which also initiate liver regeneration. Hepatocyte
      proliferation is required for liver regeneration. Zinc regulates cell
      proliferation, tissue growth, and many mitogenic signaling pathways; we
      investigated its role in hepatocytes. METHODS: Wild-type and Zip14(-/-) mice that
      underwent partial hepatectomy (70% of liver removed) were used as models of liver
      regeneration. We also analyzed AML12 hepatocytes that overexpressed Zip14.
      Proliferation was assessed with proliferating cell nuclear antigen, CD1, and Ki67
      markers and along with assays of zinc content was related to protein tyrosine
      phosphatase 1B (PTP1B) and extracellular signal-regulated kinase 1/2 signaling.
      RESULTS: Zip14 was up-regulated and hepatic zinc content increased during liver
      regeneration. Increased hepatic zinc inhibited activity of the phosphatase PTP1B
      and increased phosphorylation of c-Met, which promoted hepatocyte proliferation.
      AML12 cells that overexpressed Zip14 increased in zinc content and proliferation;
      PTP1B was inhibited and phosphorylation of c-Met increased. The increases in
      hepatic levels of zinc and hepatocyte proliferation that occurred following
      partial hepatectomy were not observed in Zip14(-/-) mice. CONCLUSIONS: The
      transporter Zip14 mediates hepatic uptake of zinc during liver regeneration and
      for hepatocyte proliferation. These findings indicate that zinc transporter
      activity regulates liver tissue growth by sequestering zinc. Reagents that
      regulate ZIP14 activity might be developed as therapeutics to promote liver
      regeneration in patients with chronic liver disease.

PMID- 22374167
TI  - DNase-activatable fluorescence probes visualizing the degradation of exogenous
      DNA in living cells.
AB  - This work presents a method to visualize the degradation of exogenous DNA in
      living cells using a novel type of activatable fluorescence imaging probe.
      Deoxyribonuclease (DNase)-activatable fluorescence probes (DFProbes) are composed
      of double strands deoxyribonucleic acid (dsDNA) which is labeled with fluorophore
      (ROX or Cy3) and quencher on the end of one of its strands, and stained with SYBR
      Green I. In the absence of DNase, DFProbes produce the green fluorescence signal
      of SYBR Green I. In the presence of DNase, SYBR Green I is removed from the
      DFProbes and the labeled fluorophore is separated from the quencher owing to the
      degradation of DFProbes by DNase, resulting in the decrease of the green
      fluorescence signal and the occurrence of a red fluorescence signal due to
      fluorescence resonance energy transfer (FRET). DNase in biological samples was
      detected using DFProbes and the fluorescence imaging in living cells was
      performed using DFprobe-modified Au nanoparticles. The results show that DFProbes
      have good responses to DNase, and can clearly visualize the degradation of
      exogenous DNA in cells in real time. The well-designed probes might be useful in
      tracing the dynamic changes of exogenous DNA and nanocarriers in vitro and in
      vivo.

PMID- 22374168
TI  - The role of iNOS inhibitors on lung injury induced by gastrointestinal
      decontamination agents aspiration.
AB  - Aspiration is a devastating complication during decontamination procedure in
      poisoning patients. We have investigated whether S-methylisothiourea protects
      different pulmonary aspiration gastrointestinal decontamination agent-induced
      lung injury in rats. Forty-two male Sprague-Dawley rats were assigned to one of
      six groups (n = 7): normal saline, activated charcoal, polyethylene glycol,
      normal saline + S-methylisothiourea treated activated charcoal + S
      methylisothiourea treated and polyethylene glycol + S-methylisothiourea treated.
      Normal saline, activated aharcoal and polyethylene glycol were instilled into the
      lungs. The rats received S-methylisothiourea i.p twice daily for 7 days. Serum
      surfactant protein D, oxidative stress products and inducible nitric oxide
      synthase expression in the lung were investigated. The aspiration of activated
      charcoal significantly increased all histopathological scores (P < 0.01). Only
      peribronchial inflammatory cell infiltration, alveolar edema, and alveolar
      histiocytes were increased in the polyethylene glycol groups as compared to the
      normal saline group (P < 0.05). Pulmonary aspiration increased serum
      malondialdehyde (P < 0.001), and surfactant protein D (P < 0.05) levels and
      decreased serum superoxide dismutase levels (P < 0.05). S-methylisothiourea
      treatment decreased all histopathological scores in the activated charcoal
      treated S-methylisothiourea group (P < 0.01) and only decreased alveolar edema
      and alveolar histiocytes in the polyethylene glycol-treated S-methylisothiourea
      group (P < 0.05). S-methylisothiourea treatment reduced elevated oxidative
      factors, inducible nitric oxide synthase activity and serum surfactant protein D
      levels. Our findings showed that S-methylisothiourea may be a protective drug
      against Activated Charcoal and Polyethylene Glycol-induced lung injury.

PMID- 22374169
TI  - Clinical significance of circulating miR-126 quantification in malignant
      mesothelioma patients.
AB  - OBJECTIVES: Aim of this study was to evaluate the accuracy and precision of the
      detection of individual miRNA as clinical biomarkers in the serum. DESIGN AND
      METHODS: miRNA-126 was quantified in serum using endogenous and exogenous
      controls for normalization and the accuracy and precision of the method
      evaluated. The diagnostic value of serum miRNA-126 was evaluated in malignant
      mesothelioma (MM) and non-small-cell lung cancer (NSCLC) patients using both
      relative and absolute qRT-PCR methods. RESULTS: The use of endogenous invariant
      and exogenous synthetic controls as well sample dilution markedly improves the
      accuracy and precision of the assay. The inter- and intra-assay analyses revealed
      that relative qRT-PCR is a more reliable method. Circulating miR-126 detected in
      the serum by relative qRT-PCRs was found low-expressed in both malignancies,
      significantly differentiated MM patients from healthy controls and NSCLC from MM,
      but do not discriminate NSCLC patients from control subjects. Kaplan-Meier
      analysis revealed that low level of circulating miR-126 in MM patients was
      strongly associated with worse prognosis. CONCLUSIONS: We propose that this
      approach can be adopted for accurate analysis of other suitable circulating miRNA
      markers of different types of cancer.

PMID- 22374170
TI  - Rapid identification of the copy number of alpha-globin genes by capillary
      electrophoresis analysis.
AB  - OBJECTIVES: The current study aimed at the rapid identification of the copy
      number of alpha-globin genes for the diagnosis of alpha-thalassemia. DESIGN AND
      METHODS: To identify the copy number of alpha-globin genes in alpha-thalassemia,
      we developed a novel method using a multiplex polymerase chain reaction (PCR) in
      combination with the CE analysis. RESULTS: The proposed method provides a rapid
      detection of the common alpha-globin gene deletions. Sixty-six patients with
      alpha-thalassemia and 46 normal controls were included in the present study. The
      obtained results showed good correlation with those obtained by gap PCR.
      Moreover, a low amount of maternal cell contamination in the fetus specimen for
      the prenatal diagnosis of hemoglobin Barts hydrops fetalis as well as the rare
      multiplicated alpha-globin genes can be identified using this method. CONCLUSION:
      This method provides a convenient and efficient tool for the rapid identification
      of the copy number of alpha-globin genes in alpha-thalassemia and the individuals
      with alpha-globin gene multiplication.

PMID- 22374171
TI  - Serum albumin is a useful prognostic indicator and adds important information to
      NT-proBNP in a Chinese cohort of heart failure.
AB  - OBJECTIVE: To evaluate the effect of serum albumin on prognosis and the power of
      albumin adding information to NT-proBNP in a Chinese cohort of heart failure.
      DESIGN AND METHODS: 385 consecutive patients (male vs. female: 292 vs. 93; mean
      age: 54.89+/-14.41years; NYHA classes II-V) admitted for heart failure
      exacerbation with LVEF<=45% were enrolled, and biochemical data was measured at
      baseline. The endpoint was defined as cardiac death or rehospitalization for
      aggravated heart failure. Follow-up period was 25+/-7months. RESULTS:
      Multivariate analysis in a Cox proportional hazard model revealed serum albumin
      was an independent predictor for adverse prognosis (HR 0.96,CI 0.94-0.99,
      P=0.02), and the patients with higher NT-proBNP and lower albumin than median had
      the highest risk for cardiac events (HR 2.89, CI 1.90-4.40, P<0.01). CONCLUSION:
      Serum albumin is a significant prognosis indicator for heart failure and it adds
      important information to NT-proBNP.

PMID- 22374172
TI  - Development of a method for the quantitative analysis of urinary stones, formed
      by a mixture of two components, using infrared spectroscopy.
AB  - OBJECTIVES: The analysis of urinary stones is used for the diagnosis of the
      etiology of an episode of nephrolithiasis. The technique considered as standard
      for this purpose is infrared spectroscopy (IR). However, when the urinary stone
      is formed by a mixture of components, only semi-quantitative information can be
      achieved using IR. The objective of this work is the development of a
      quantitative method. DESIGN AND METHODS: Bands in the IR spectra of several
      mixtures were studied, in order to design a calibration model useful to determine
      the quantitative composition of the urinary stones. For mixtures of two
      components, four mathematical models were proposed. To assess the validity of
      these models, nine series of mixtures of two components were prepared, using the
      most frequently compounds found in urinary stones, for analyzing by ATR-FTIR
      spectroscopy (Attenuated Total Reflection Fourier Transformed Infrared). RESULTS:
      Nine series of nine mixtures of two components were prepared for this work. The
      IR spectrum was recorded for each mixture and the absorbance intensities at
      selected wave numbers were used to apply the proposed mathematical models. There
      were good linear correlations between the analytical signals (IR absorbances) and
      the analytical responses (weight fractions) using the calibration lines. The
      validity of the method was checked by the comparison between the weight fractions
      resulted from the calibration lines and the real weight fractions obtained by
      weighing, presenting good correlation parameters. CONCLUSIONS: The method
      developed in this work has been useful for the quantification of compounds which
      are commonly found in urinary stones. This method allows a total characterization
      of the urinary stones (qualitative and quantitative) by means of IR spectroscopy.

PMID- 22374173
TI  - Didocosyl selenide stabilized recyclable Pd(0) nanoparticles and coordinated
      palladium(II) as efficient catalysts for Suzuki-Miyaura coupling.
AB  - First selenium ligand stabilized Pd(0) nanoparticles (~3-5 nm) catalyze Suzuki
      Miyaura C-C coupling in short time and are recyclable (up to 94% yield after 5
      reuses). The air stable compound [PdCl(2)(L1)(2)] shows high catalytic efficiency
      for this coupling as its 3 * 10(-5) mol% is sufficient for activated ArBr.

PMID- 22374174
TI  - Tracking motor improvement at the subtask level during robot-aided
      neurorehabilitation of stroke patients.
AB  - BACKGROUND: Robot-aided neurorehabilitation can provide intensive, repetitious
      training to improve upper-limb function after stroke. To be more effective, motor
      therapy ought to be progressive and continuously challenge the patient's ability.
      Current robotic systems have limited customization capability and require a
      physiotherapist to assess progress and adapt therapy accordingly. OBJECTIVE: The
      authors aimed to track motor improvement during robot-assistive training and test
      a tool to more automatically adjust training. METHODS: A total of 18 participants
      with chronic stroke were trained using a multicomponent reaching task assisted by
      a shoulder-elbow robotic assist. The time course of motor gains was assessed for
      each subtask of the practiced exercise. A statistical algorithm was then tested
      on simulated data to validate its ability to track improvement and subsequently
      applied to the recorded data to determine its performance compared with a
      therapist. RESULTS: Patients' recovery of motor function exhibited a time course
      dependent on the particular component of the executed task, suggesting that
      differential training on a subtask level is needed to continuously challenge the
      neuromuscular system and boost recovery. The proposed algorithm was tested on
      simulated data and was proven to track overall patient's progress during
      rehabilitation. CONCLUSIONS: Tuning of the training program at the subtask level
      may accelerate the process of motor relearning. The algorithm proposed to adjust
      task difficulty opens new possibilities to automatically customize robotic
      assistive training.

PMID- 22374175
TI  - Identification of long non-protein coding RNAs in chicken skeletal muscle using
      next generation sequencing.
AB  - Vertebrate genomes encode thousands of non-coding RNAs including short non-coding
      RNAs (such as microRNAs) and long non-coding RNAs (lncRNAs). Chicken (Gallus
      gallus) is an important model organism for developmental biology, and the
      recently assembled genome sequences for chicken will facilitate the understanding
      of the functional roles of non-coding RNA genes during development. The present
      study concerns the first systematic identification of lncRNAs using RNA-Seq to
      sample the transcriptome during chicken muscle development. A computational
      approach was used to identify 281 new intergenic lncRNAs in the chicken genome.
      Novel lncRNAs in general are less conserved than protein-coding genes and
      slightly more conserved than random non-coding sequences. The present study has
      provided an initial chicken lncRNA catalog and greatly increased the number of
      chicken ncRNAs in the non-protein coding RNA database. Furthermore, the
      computational pipeline presented in the current work will be useful for
      characterizing lncRNAs obtained from deep sequencing data.

PMID- 22374176
TI  - Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and
      cardiac fibrosis in the db/db mouse model of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: An increase in the production of reactive oxygen species is
      commonly thought to contribute to the development of diabetic cardiomyopathy.
      This study aimed to assess whether administration of the antioxidant coenzyme
      Q(10) would protect the diabetic heart against dysfunction and remodelling, using
      the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the
      efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril. METHODS: Six
      week-old non-diabetic db/+ mice and diabetic db/db mice received either normal
      drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint
      cardiac function was assessed by echocardiography and catheterisation.
      Ventricular tissue was collected for histology, gene expression and protein
      analysis. RESULTS: Untreated db/db diabetic mice exhibited hyperglycaemia,
      accompanied by diastolic dysfunction and adverse structural remodelling,
      including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis.
      Systemic lipid peroxidation and myocardial superoxide generation were also
      elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide
      generation, ameliorated diastolic dysfunction and reduced cardiomyocyte
      hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although
      depressed in untreated db/db mice, was restored with coenzyme Q(10)
      administration. We postulate that preservation of cardioprotective Akt signalling
      may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from
      pathological cardiac hypertrophy. CONCLUSIONS/INTERPRETATION: These data
      demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular
      diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme
      Q(10) to the current therapy used in diabetic patients with diastolic dysfunction
      warrants further investigation.

PMID- 22374177
TI  - Dorsolateral medullary ischemic infarction causing autonomic dysfunction and
      headache: a case report.
AB  - Stroke can present, among other signs, with headache. Here, we describe the case
      of a man suffering from severe orbitary pain and autonomic dysfunction secondary
      to dorsolateral medullary ischemia. The anatomical relationship between lesion
      and symptomatology could be an indirect sign of hypothalamospinal tract
      involvement in the genesis of autonomic dysfunction and headache resembling a
      trigeminal autonomic cephalalgia.

PMID- 22374178
TI  - Cellular neuroanatomy: primary cilia, the key to integration.

PMID- 22374179
TI  - Behavioural neuroscience: taking axonal delivery of oxytocin.

PMID- 22374180
TI  - Suicides in a mega-size factory in China: poor mental health among young migrant
      workers in China.

PMID- 22374181
TI  - Importance of transient receptor potential vanilloid 4 (TRPV4) in epidermal
      barrier function in human skin keratinocytes.
AB  - The state of the skin changes drastically depending on the ambient temperature.
      Skin epidermal keratinocytes express thermosensitive transient receptor potential
      vanilloid (TRPV) cation channels, TRPV3 and TRPV4. These multimodal receptors are
      activated by various kinds of chemical and physical stimuli, including warm
      temperatures (>30 degrees C). It has been suggested that TRPV4 is involved in
      cell-cell junction maturation; however, the effect of temperature fluctuations on
      TRPV4-dependent barrier homeostasis is unclear. In the present study, we
      demonstrated that activation of TRPV4 was crucial for barrier formation and
      recovery, both of which were critical for the prevention of excess dehydration of
      human skin keratinocytes. TRPV4 activation by physiological skin temperature (33
      degrees C), GSK1016790A or 4alpha-PDD allowed influx of Ca(2+) from extracellular
      spaces which promoted cell-cell junction development. These changes resulted in
      augmentation of intercellular barrier integrity in vitro and ex vivo. TRPV4
      disruption reduced the increase in trans-epidermal resistance and increased
      intercellular permeation after a Ca(2+) switch. Furthermore, barrier recovery
      after the disruption of the stratum corneum was accelerated by the activation of
      TRPV4 either by warm temperature or a chemical activator. Our results suggest
      that physiological skin temperatures play important roles in cell-cell junction
      and skin barrier homeostasis through TRPV4 activation.

PMID- 22374182
TI  - Staining of Bartonella henselae with carboxyfluorescein diacetate succinimidyl
      ester for tracking infection in erythrocytes and epithelial cells.
AB  - Bartonella infection (Bartonella henselae in particular) is responsible for a
      widening spectrum of human diseases. The persistent colonization of erythrocytes
      is a feature of Bartonella infection. Endothelial and epithelial cells are also
      widely used to study the pathogenesis of bartonellosis in vitro. Exploring a
      convenient method for visualizing the bacillus without affecting infectivity
      would be very interesting. Carboxyfluorescein diacetate succinimidyl ester (CFSE)
      has been previously used for staining several bacterial species to study their
      adhesion to host cells. The present study demonstrated the efficiency and safety
      of using CFSE in staining B. henselae. The staining of bacillus-invaded
      erythrocytes and epithelial cells in vitro successfully allowed for flow
      cytometry and confocol microscopy analyses. Parallel tests using untreated
      bacteria confirmed that CFSE staining did not result in side effects on the
      infectivity of B. henselae. Labeling Bartonella with CFSE is a valuable method
      for studying the bacteria-host interaction.

PMID- 22374183
TI  - Cardiac biomarkers are associated with an increased risk of stroke and death in
      patients with atrial fibrillation: a Randomized Evaluation of Long-term
      Anticoagulation Therapy (RE-LY) substudy.
AB  - BACKGROUND: Cardiac biomarkers are strong predictors of adverse outcomes in
      several patient populations. We evaluated the prevalence of elevated troponin I
      and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association
      to cardiovascular events in atrial fibrillation (AF) patients in the Randomized
      Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. METHODS AND
      RESULTS: Biomarkers at randomization were analyzed in 6189 patients. Outcomes
      were evaluated by Cox proportional hazards models adjusting for established
      cardiovascular risk factors and the CHADS(2) and CHA(2)DS(2)-VASc risk scores.
      Patients were stratified based on troponin I concentrations: <0.010 MUg/L,
      n=2663; 0.010 to 0.019 MUg/L, n=2006; 0.020 to 0.039 MUg/L, n=1023; >=0.040
      MUg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to
      1402; >1402 ng/L. Rates of stroke were independently related to levels of
      troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I
      group (hazard ratio [HR], 1.99 [95% CI, 1.17-3.39]; P=0.0040), and to NT-proBNP
      with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile
      groups, (HR, 2.40 [95% CI, 1.41-4.07]; P=0.0014). Vascular mortality was also
      independently related to biomarker levels with 6.56%/year in the highest and
      1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05-6.29]; P<0.0001),
      and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile
      groups (HR, 6.73 [3.95-11.49]; P<0.0001). Biomarkers increased the C-statistic
      from 0.68 to 0.72, P<0.0001, for a composite of thromboembolic events.
      CONCLUSIONS: Elevations of troponin I and NT-proBNP are common in patients with
      AF and independently related to increased risks of stroke and mortality. Cardiac
      biomarkers seem useful for improving risk prediction in AF beyond currently used
      clinical variables.

PMID- 22374184
TI  - Anxiety disrupts the evaluative component of performance monitoring: An ERP
      study.
AB  - Thirty low and 30 high anxious participants performed a speeded Go/noGo task
      during which they had to rely on evaluative feedback to infer whether their
      actions were timely (correct) or not. We focused on FRN, an ERP component that is
      sensitive to the valence of feedback. Depending on the context, neutral faces
      served either as positive or negative feedback. Whereas the FRN of low anxious
      individuals did discriminate between neutral faces when used either as positive
      or negative feedback, the FRN of high anxious individuals did not. However,
      before the FRN, we also found evidence for a differential perceptual effect at
      the level of the N170 face-specific component between the two feedback
      conditions, equally so in low and high anxious individuals. These results suggest
      that anxiety disrupts selectively the evaluative component of performance
      monitoring, which presumably allows to ascribe a given value (either positive or
      negative) to actions.

PMID- 22374185
TI  - CCL5-28, CCL5-403, and CCR5 genetic polymorphisms and their synergic effect with
      alcohol and tobacco consumptions increase susceptibility to hepatocellular
      carcinoma.
AB  - The aim of this study was to estimate the relationship between gene polymorphisms
      of CCL5-28, CCL5-403, and CCR5 to the susceptibility of hepatocellular carcinoma
      (HCC). A total of 449 subjects, including 347 healthy controls and 102 patients
      with HCC, were recruited in this study and subjected to polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) to investigate the impact of
      these two polymorphic variants on HCC. A significant association between HCC
      susceptibility and genetic polymorphism, CG heterozygotes of CCL5-28 (AOR=2.35;
      95% CI=1.27-4.33, p=0.006), AA homozygotes of CCL5-403 (AOR=5.18; 95% CI=2.25
      11.91, p=0.0001), and AA homozygotes of CCR5 (AOR=2.47; 95% CI=1.24-4.90,
      p=0.009), was found compared with wild genotype after adjusting for other
      confounders. It was detected that synergistic effect between gene-to-gene
      polymorphisms increased the risk to have HCC among individuals with CG or GG of
      CCL5-28, and GA or AA of CCL-403, and GA or AA of CCR5 (AOR=3.42; 95% CI=1.39
      8.38, p=0.007) compared to individuals with wild genotypes of CCL5-28, CCL-403,
      and CCR5. Also, alcohol or tobacco consumption increased the risk to have HCC
      among subjects with CG heterozygotes of CCL5-28 (alcohol: p=0.001; tobacco:
      p=0.006), AA homozygotes (alcohol: p=0.0004; tobacco: p<=0.0001) or GA
      heterozygotes (tobacco: p=0.03) of CCL5-403, and AA homozygotes of CCR5 (alcohol:
      p=0.02; tobacco: p=0.02), respectively. Gene polymorphisms of CCL5-28, CCL5-403,
      and CCR5 play an important factor for the susceptibility of HCC, respectively.
      The synergic effects of these two gene polymorphisms to tobacco or alcohol
      consumption significantly increase the risk to develop HCC.

PMID- 22374186
TI  - Successful implementation of the american college of surgeons/association of
      program directors in surgery surgical skills curriculum via a 4-week consecutive
      simulation rotation.
AB  - INTRODUCTION: Increased patient awareness, duty hour restrictions, escalating
      costs, and time constraints in the operating room have revolutionized surgery
      education. Although simulation and skills laboratories are emerging as promising
      alternatives for skills training, their integration into graduate surgical
      education is inconsistent, erratic, and often on a voluntary basis. We
      hypothesize that, by implementing the American College of Surgeons/Association of
      Program Directors in Surgery Surgical Skills Curriculum in a structured,
      inanimate setting, we can address some of these concerns. METHODS: Sixty junior
      surgery residents were assigned to the Penn Surgical Simulation and Skills
      Rotation. The National Surgical Skills Curriculum was implemented using multiple
      educational tools under faculty supervision. Pretraining and posttraining
      assessments of technical skills were conducted using validated instruments.
      Trainee and faculty feedbacks were collected using a structured feedback form.
      RESULTS: Significant global performance improvement was demonstrated using
      Objective Structured Assessment of Technical Skills score for basic surgical
      skills (knot tying, wound closure, enterotomy closure, and vascular anastomosis)
      and Fundamentals of Laparoscopic Surgery skills, P < 0.001. Six trainees were
      retested on an average of 13.5 months later (range, 8-16 months) and retained
      more than 75% of their basic surgical skills. DISCUSSION: The American College of
      Surgeons/Association of Program Directors in Surgery National Surgical Skills
      Curriculum can be implemented in its totality as a 4-week consecutive surgical
      simulation rotation in an inanimate setting, leading to global enhancement of
      junior surgical residents' technical skills and contributing to attainment of
      Accreditation Council for Graduate Medical Education core competency.

PMID- 22374187
TI  - Biosorption of Cr(VI) by free and immobilized Pediastrum boryanum biomass:
      equilibrium, kinetic, and thermodynamic studies.
AB  - BACKGROUND AND PURPOSE: The biosorption of Cr(VI) from aqueous solution has been
      studied using free and immobilized Pediastrum boryanum cells in a batch system.
      The algal cells were immobilized in alginate and alginate-gelatin beads via
      entrapment, and their algal cell free counterparts were used as control systems
      during biosorption studies of Cr(VI). METHODS: The changes in the functional
      groups of the biosorbents formulations were confirmed by Fourier transform
      infrared spectra. The effect of pH, equilibrium time, initial concentration of
      metal ions, and temperature on the biosorption of Cr(VI) ion was investigated.
      RESULTS: The maximum Cr(VI) biosorption capacities were found to be 17.3, 6.73,
      14.0, 23.8, and 29.6 mg/g for the free algal cells, and alginate, alginate
      gelatin, alginate-cells, and alginate-gelatin-cells at pH 2.0, which are
      corresponding to an initial Cr(VI) concentration of 400 mg/L. The biosorption of
      Cr(VI) on all the tested biosorbents (P. boryanum cells, alginate, alginate
      gelatin, and alginate-cells, alginate-gelatin-cells) followed Langmuir adsorption
      isotherm model. CONCLUSION: The thermodynamic studies indicated that the
      biosorption process was spontaneous and endothermic in nature under studied
      conditions. For all the tested biosorbents, biosorption kinetic was best
      described by the pseudo-second-order model.

PMID- 22374188
TI  - BOD biosensors for pulp and paper industry wastewater analysis.
AB  - INTRODUCTION: Two semi-specific microbial biosensors were constructed for the
      analysis of biochemical oxygen demand (BOD) in high-cellulose-content pulp and
      paper industry wastewaters. The biosensors were based on living cells of Bacillus
      subtilis and Paenibacillus sp. immobilized in an agarose gel matrix. Semi
      specific microorganisms were isolated from various samples (decaying sawdust and
      rabbit manure) and were chosen based on their ability to assimilate cellulose.
      MATERIALS & METHODS: The biosensors were calibrated with the Organization for
      Economic Cooperation and Development synthetic wastewater, and measurements with
      different wastewaters were conducted. RESULTS: The response time of biosensors
      using the steady-state method was 20-25 min, and the service life of immobilized
      microorganisms was 96 days. Detection limit was 5 mg/l of BOD(7) while linear
      ranges extended up to 55 and 50 mg/l of the BOD(7) for B. subtilis- and
      Paenibacillus sp.-based biosensors, respectively. Repeatability and
      reproducibility of both biosensors were within the limits set by APHA-less than
      15.4%. In comparison, both biosensors overestimated the BOD(7) values in paper
      mill wastewaters and underestimated the BOD(7) in aspen pulp mill wastewater.
      CONCLUSIONS: The semi-specific biosensors are suitable for the estimation of
      organic pollution derived from cellulose, while the detection of pollution
      derived from tannins and lignins was minor. Better results in terms of accuracy
      and repeatability were gained with Paenibacillus sp. biosensor.

PMID- 22374189
TI  - About exposure data used in paper "assessing the potential exposure risk and
      control for airborne titanium dioxide and carbon black nanoparticles in the
      workplace".

PMID- 22374190
TI  - Blooming of Microcystis aeruginosa in the reservoir of the reclaimed land and
      discharge of microcystins to Isahaya Bay (Japan).
AB  - PURPOSE: In the reservoir created in the reclaimed land in Isahaya Bay, Japan,
      Microcystis aeruginosa, which produces microcystins (MCs), bloomed every year,
      and the water with high levels of MCs in the reservoir has been often drained to
      Isahaya Bay to adjust the water level. The principal aims of this study are to
      clarify the water conditions suitable for blooming of M. aeruginosa in the
      reservoir, to follow the amount of distribution of MCs inside and outside the
      reservoir, and to discuss how blooming of M. aeruginosa is controlled in the
      reservoir and how MCs produced by Microcystis spread or accumulate in the aquatic
      environment. METHOD: We monitored the water quality (temperature, salinity,
      dissolved inorganic nitrogen (DIN), and dissolved inorganic phosphorus) in the
      reservoir with seasonal blooming of microalgae including phytoplankton and M.
      aeruginosa using the concentrations of chlorophyll alpha and MCs, respectively,
      and collected the surface sediment in the reservoir and the bay to determine the
      MC content using the ELISA method. RESULT: M. aeruginosa bloomed in extremely low
      DIN conditions of the water in warm seasons (spring and late summer to autumn).
      The year-mean standing stock of MCs was approximately 34.5 kg in the water and
      8.4 kg in the surface sediment in the reservoir. Approximately 64.5 kg of MCs was
      discharged with the effluent to the bay in a year. CONCLUSION: Since a large
      amount of MCs always suspends in the water in the reservoir and it has been
      discharged to the bay, suspension-feeding animals are exposed most seriously to
      the high levels of MCs occurring in these areas. We need to pay attention to the
      danger of widespread dispersal of MCs and biological concentration of MCs by fish
      and clam inside and outside the reservoir.

PMID- 22374191
TI  - Environmental lead pollution threatens the children living in the Pearl River
      Delta region, China.
AB  - INTRODUCTION AND PURPOSE: The objective of this study is to determine children's
      blood lead levels and identify sources of lead exposure. Childhood lead exposure
      constitutes a major pediatric health problem today in China. A blood lead
      screening survey program for children in the age group of 2-12 years residing in
      Pearl River Delta region, south of China, was carried out from Dec 2007 to Jan
      2008. METHODS: Blood lead levels and lead isotope ratios of a total of 761
      participants were assessed by inductively coupled plasma mass spectroscopy.
      Measurements of urban environmental samples for source identification of children
      lead exposure were also performed. RESULTS AND CONCLUSIONS: The geometric mean
      value of the children's blood lead levels was 57.05 MUg/L, and 9.6% of them were
      higher than 100 MUg/L. The blood lead levels were still much higher than those in
      developed countries. Based on the data of environmental lead source inventories,
      lead isotopic tracing revealed that there is about 6.7% past used gasoline Pb
      embedded in Shenzhen residential dust and about 15.6% in Guangzhou dust,
      respectively.

PMID- 22374192
TI  - Public versus private: evidence on health insurance selection.
AB  - This paper models health insurance choice in Chile (public versus private) as a
      dynamic, stochastic process, where individuals consider premiums, expected out-of
      pocket costs, personal characteristics and preferences. Insurance amenities and
      restrictions against pre-existing conditions among private insurers introduce
      asymmetry to the model. We confirm that the public system services a less healthy
      and wealthy population (adverse selection for public insurance). Simulation of
      choices over time predicts a slight crowding out of private insurance only for
      the most pessimistic scenario in terms of population aging and the evolution of
      education. Eliminating the restrictions on pre-existing conditions would slightly
      ameliorate the level (but not the trend) of the disproportionate accumulation of
      less healthy individuals in the public insurance program over time.

PMID- 22374193
TI  - Mouse sensitization as an independent risk factor for asthma morbidity.

PMID- 22374194
TI  - Clinical and cytologic characteristics of allergic rhinitis in elderly patients.
AB  - BACKGROUND: The constant increase in the elderly population worldwide has led to
      a greater interest in immunologic responses during aging. Thus, special attention
      to allergic diseases in elderly people has begun to emerge, but little is known
      about the effect and features of allergic rhinitis in elderly people. OBJECTIVE:
      To evaluate the clinical and cytologic characteristics of respiratory allergy and
      its impact on the quality of life in elderly people. METHODS: Elderly patients
      with rhinitis referred to our allergy unit during a 3-month period underwent
      clinical evaluation and responded to the Rhinasthma Questionnaire. All patients
      also underwent skin prick testing, measurement of total IgE level, and nasal
      cytologic analysis. The data were compared with a control group of young adults.
      RESULTS: Fifty-four patients older than 65 years (mean age, 69.3 years) and 89
      young adults (mean age, 26.3 years) with allergic rhinitis were studied. The
      elderly patients had a less positive family history of atopy (P=.02) and had
      rhinitis plus conjunctivitis more frequently (P=.002) than young adults, whereas
      the difference between groups in total IgE level was not statistically
      significant. On nasal cytologic analysis, the differential count of inflammatory
      cells did not differ between groups, but in the elderly patients the epithelial
      goblet cell ratio was decreased. The quality of life in elderly people was more
      impaired than in young adults (P=.01). CONCLUSION: In elderly people with
      allergic rhinitis, the clinical characteristics are different and quality of life
      is more heavily impaired compared with young adults.

PMID- 22374195
TI  - Genetic variation in small proline rich protein 2B as a predictor for asthma
      among children with eczema.
AB  - BACKGROUND: Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial
      protein associated with allergic inflammation in mice that has not been evaluated
      in human atopic diseases. OBJECTIVE: To determine whether single-nucleotide
      polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the
      phenotype of childhood eczema combined with asthma. METHODS: Genotyping for
      SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the
      Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4
      years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR; N = 1152;
      ages 5-10 years). Eczema and eczema plus asthma were clinical outcomes based on
      parental report and clinician's diagnosis. Genetic analyses were restricted to
      whites and adjusted for sex in both cohorts and adjusted for environmental
      covariates in CCAAPS. RESULTS: Variants in SPRR2B were not significantly
      associated with eczema in either cohort after Bonferroni adjustment. Children
      from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4
      times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence
      interval, 1.5-10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95%
      confidence interval, 1.8-9.1; P < .001 in the GCPCR), however. SNPs in SPRR2B
      were not in strong linkage disequilibrium with the R501X and del2282 FLG
      mutations, and these findings were independent of FLG. CONCLUSIONS: An SNP in
      SPRR2B was predictive of asthma among white children with eczema from 2
      independent populations. SPRR2B polymorphisms may serve as important predictive
      markers for the combined eczema plus asthma phenotype.

PMID- 22374196
TI  - Diagnostic utility of exhaled breath condensate analysis in conjunction with
      specific inhalation challenge in individuals with suspected work-related asthma.
AB  - BACKGROUND: Establishing the role of exhaled breath condensate (EBC) analysis in
      work-related asthma (WRA), and more specifically, in conjunction with specific
      inhalation challenge (SIC), is difficult. OBJECTIVE: To measure EBC pH, and
      nitrite/nitrate concentrations before and after SIC in individuals with suspected
      WRA exposed to either high-molecular-weight (HMW) or low-molecular-weight (LMW)
      agents and evaluate whether these changes are useful to distinguish between
      occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS: One hundred
      twenty-five consecutive workers undergoing SIC were enrolled. Exhaled breath
      condensate was collected at the end of the baseline day and 24 hours after
      exposure to the offending agent. In all EBC samples, pH was measured, and nitrite
      and nitrate concentrations were determined. RESULTS: Specific inhalation
      challenge was positive in 66 individuals, who were then diagnosed with OA. Work
      exacerbated asthma was diagnosed in 14, and in 45 patients establishing a direct
      relationship between the symptoms and work exposure was not possible. In patients
      with WEA, EBC pH values after SIC were significantly lower than those before SIC
      (P = .0047). Using the receiver operating characteristic (ROC) curve, we found
      that an EBC pH decrease of greater than 0.4 units after SIC achieved the most
      satisfactory sensitivity 79% (confidence interval [CI]: 49-94) and specificity of
      100% (CI: 68-100), considering only patients with asthma and without OA. A
      decrease in EBC pH of 0.4 or more common in those exposed to HMW agents (8/19,
      42%) than in those exposed to LMW agents (7/47, 15%). CONCLUSIONS: Exhaled breath
      condensate pH in conjunction with SIC may be useful for diagnosing WEA.

PMID- 22374198
TI  - Allergic conjunctivitis and dry eye syndrome.
AB  - BACKGROUND: Allergic conjunctivitis (AC) and dry eye syndrome (DES) are 2 of the
      most common anterior inflammatory disorders of the ocular surface and one does
      not preclude the coexistence of the other. OBJECTIVES: To examine the potential
      overlap between AC and DES as comorbidities. METHODS: Using the validated
      questionnaire known as Subjective Evaluation of Symptom of Dryness, we studied
      self-reported itchiness, dryness, and redness. In an outpatient optometric
      setting, 689 patients treated from January 1, 2007, to January 1, 2011, were
      surveyed for their ocular history and categorized according to their reported
      level of discomfort of itchiness, dryness, and redness. RESULTS: Patients ranged
      in age from 5 to 90 years (median age, 25 years; 39.5% male; 60.5% female). In
      the studied 689 patients, clinically significant itchiness was found in 194
      (28.2%), dry eyes in 247 (35.8%), and redness in 194 (28.2%). Symptom overlap was
      demonstrated in many of the patients. Of the 194 patients with itchiness, 112
      (57.7%) had clinically significant dryness. In the 247 patients with dry eyes,
      112 (45.3%) had clinically significant itch. Redness was apparent in 120 of the
      194 patients with itch (61.9%) and 122 of the 247 patients with dryness (49.4%).
      Statistical analysis demonstrated that self-reported itchiness, dryness, and
      redness were not independent of each other (P<.001; Pearson chi(2) test). The
      odds of patients with "itchy eyes" also experiencing dry eyes were 2.11 times and
      the odds of these patients also experiencing redness were 7.34 times that of
      patients with nonitchy eyes. CONCLUSIONS: Most patients with "itchy eyes"
      consistent with AC also have dry eyes and redness. These results suggest that
      some symptomatic patients concomitantly have features of AC and DES.

PMID- 22374197
TI  - The CHOICE survey: high rates of persistent and uncontrolled asthma in the United
      States.
AB  - BACKGROUND: Surveys have consistently shown that many patients with asthma do not
      have their disease well controlled. OBJECTIVES: The CHOICE (Comprehensive Survey
      of Healthcare Professionals and Asthma Patients Offering Insight on Current
      Treatment Gaps and Emerging Device Options) survey was designed to evaluate the
      current status of inhalation devices used in asthma treatment, but questions also
      were included about asthma severity and control. METHODS: A total of 1,000
      patients with asthma were interviewed about their use of inhalation devices and
      asthma-related burden, medication use, and hospital/emergency care. Based on the
      responses to these questions, asthma severity and control were categorized using
      methods established in the Expert Panel Report III (EPR 3). RESULTS: Almost half
      (490) of the patients with asthma participating in the CHOICE survey were not
      using controller medications. Most of those not using controllers (79%) had
      persistent asthma; 47% had either mild or moderate persistent asthma. Of those on
      controllers (510), only 14.3% were well controlled. Acute care utilization was
      greater for patients with persistent asthma than those with intermittent asthma
      and for patients with not well and poorly controlled asthma than those with well
      controlled asthma. CONCLUSION: The CHOICE survey is particularly pertinent
      clinically, because it demonstrates for the first time, using EPR 3 methods, the
      current extent of poor asthma control in the United States. This situation falls
      far short of national asthma management targets.

PMID- 22374199
TI  - Surveillance of contrast-media-induced hypersensitivity reactions using signals
      from an electronic medical recording system.
AB  - BACKGROUND: Contrast-media (CM) hypersensitivity is a well-known adverse drug
      reaction. Surveillance of adverse drug reactions usually depends on spontaneous
      reports. However, the rate of spontaneous reports is low. Recent progress in
      information technology enables the electronic search on signals of adverse drug
      reactions from electronic medical recording (EMR) systems. OBJECTIVES: To analyze
      the incidence and clinical characteristics of CM hypersensitivity using an EMR
      based surveillance system. METHODS: The surveillance system used signals from
      standardized terms within the international classification of nursing practice
      terms that can indicate symptoms of CM hypersensitivity and from the order codes
      for procedures that used contrast media, antihistamine, and epinephrine. The
      search strategy was validated by allergists comparing the electronic search
      strategy versus manually reviewing medical charts over one month. The main study
      covered for one year period. RESULTS: Detection rate of the electronic search
      method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759).
      EMR-based electronic search method was highly efficient: reduced the charts that
      needed to be reviewed by 96% (28/759). The sensitivity of electronic screening
      was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM
      hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria
      was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%)
      that induced CM hypersensitivity. CONCLUSION: A surveillance system using EMR may
      be a useful tool in the study of drug hypersensitivity epidemiology and may be
      used in an adverse drug reaction alarm system and as a clinical, decision making
      support system.

PMID- 22374200
TI  - Expression of nitric oxide synthases in leukocytes in nasal polyps.
AB  - BACKGROUND: Nitric oxide (NO) has various roles in airway physiology and
      pathophysiology. Monitoring exhaled NO levels is increasingly common to measure
      airways inflammation and inhaled NO studied for its therapeutic value in
      premature infants and adult respiratory distress syndrome. NO is produced by 3
      isoforms of NO synthase (NOS1, 2, 3), and each can play distinct and perhaps
      overlapping roles in the airways. However, the distribution, regulation, and
      functions of NOS in various cells in the upper airways, particularly in
      leukocytes, are incompletely understood. OBJECTIVE: To characterize the
      expression of NOS isoforms in leukocytes in normal middle turbinate tissues (MT)
      and in inflammatory nasal tissue (nasal polyps, NP). METHODS: Normal MT tissue
      was collected from surgical specimens that were to be discarded. The NP samples
      were from surgical tissue archives of 15 patients with chronic rhinosinusitis.
      Isoforms of NOS in cells were identified by double immunostaining using NOS
      isoform-specific and leukocyte-specific (mast cell, eosinophil, macrophage,
      neutrophil, or T cell) antibodies. RESULTS: The proportion of total cells below
      the epithelium that were positive for each isoform of NOS was higher in NP than
      in MT. Each isoform of NOS was found in all leukocyte populations studied, and
      there were significant differences in the percentage of leukocytes expressing NOS
      isoforms between MT and NP. CONCLUSION: All isoforms of NOS are expressed in
      leukocytes in MT and NP, and their expression varies among leukocyte types. Our
      data provide a basis to investigate the regulation, cell distribution, and
      distinct functions of NOS isoforms in normal and inflamed nasal tissues.

PMID- 22374201
TI  - Characterization of occupational sensitization by multiallergen immunoblotting in
      workers exposed to laboratory animals.
AB  - BACKGROUND: Studies have estimated that 10% to 23% of workers exposed to
      laboratory animals report symptoms of laboratory animal allergy. OBJECTIVES: To
      determine the level of occupational sensitization in workers exposed to
      laboratory animals and to develop a diagnosis system based on a multiallergen IgE
      immunoblot. METHODS: A total of 75 workers exposed to laboratory animals were
      initially studied with skin prick tests performed with animal epithelia extracts.
      The workers with suspected occupational disease and positive skin prick test
      results were further studied with the ImmunoCAP system to determine specific IgE
      levels to urine and epithelia allergens and with multiallergen IgE immunoblotting
      to detect specific IgE levels to epithelia allergens and bovine serum albumin.
      RESULTS: Twenty of the 75 workers were studied with ImmunoCAP and multiallergen
      IgE immunoblotting. Nine were polysensitized and 3 were sensitized to only one
      animal. The results obtained by ImmunoCAP and multiallergen IgE immunoblotting
      were concordant except for in 3 workers, who had low or negative values of
      specific IgE determined by ImmunoCAP but positive allergen detections by
      immunoblotting. On the basis of the results of the study and the clinical
      symptoms related by workers, 16% were diagnosed as having occupational allergy.
      CONCLUSIONS: Multiallergen immunoblotting by means of a unique test offers a
      graphic representation of sensitization to the different animals to which workers
      are exposed, providing additional information on the clinical symptoms caused by
      the involved allergens. The results presented suggest that this system can
      improve the diagnosis of laboratory animal allergy by obtaining a sensitization
      profile for each exposed worker.

PMID- 22374203
TI  - Omalizumab inhibits acceleration of FcepsilonRI-mediated responsiveness of
      immature human mast cells by immunoglobulin E.
AB  - BACKGROUND: A large body of evidence has demonstrated that treatment with
      omalizumab is clinically effective for the management of moderate to severe
      allergic asthma, emphasizing the importance of IgE in the pathogenesis of
      allergic asthma. We hypothesized that IgE accelerates FcepsilonRI-mediated
      responsiveness of "immature" human mast cells (MCs) and that omalizumab
      downregulates the acceleration. OBJECTIVES: To examine when MC progenitors
      acquired the ability to degranulate following FcepsilonRI aggregation, whether
      IgE accelerates the responsiveness of immature MCs following FcepsilonRI
      aggregation, and whether omalizumab regulates such an acceleration. METHODS: Gene
      expression was examined using a microarray and quantitative reverse transcription
      polymerase chain reaction. Protein expression was investigated using FACS.
      Histamine release was examined using an EIA. RESULTS: The time-course analysis of
      the mRNA expression of MC-related genes, including FcepsilonRI, in Kit(+) sorted
      cells during the differentiation and histamine experiments revealed that the
      expression level of FcepsilonRI in 5 week (w)-cultured MCs was not sufficient to
      induce degranulation following FcepsilonRI aggregation but that 5 w-cultured MCs
      were fully responsive to calcium ionophore. By addition of IgE in culture medium
      FcepsilonRI expression level and FcepsilonRI-mediated histamine release of 5 w
      cultured MCs were significantly increased compared with those without addition of
      IgE, whereas the expression level of tryptase and number of MCs was not affected.
      Omalizumab significantly inhibited IgE-dependent enhancement of FcepsilonRI
      expression level and FcepsilonRI-mediated histamine release. CONCLUSIONS: High
      levels of IgE in the microenvironment in vivo may upregulate the responsiveness
      of immature MCs to allergens. Omalizumab may inhibit the IgE-mediated
      responsiveness of not only mature MCs, but also immature MCs.

PMID- 22374202
TI  - Effects of rhinovirus infection on the expression and function of cystic fibrosis
      transmembrane conductance regulator and epithelial sodium channel in human nasal
      mucosa.
AB  - BACKGROUND: Changes in expression and function of the cystic fibrosis
      transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC)
      have been found to cause airway surface liquid (ASL) derangement and to impair
      mucociliary clearance, both of which have been linked to the pathogenesis of
      rhinovirus (RV) infection. OBJECTIVES: The effects of RV infection on the
      expression and function of CFTR and ENaC in nasal epithelial cells were
      investigated. METHODS: Nasal epithelial cells obtained from 14 turbinoplasty
      patients were infected with RV serotype 16 (RV-16) for 4 hours. Expression of
      CFTR, alpha-ENaC, beta-ENaC, and gamma-ENaC was determined by real-time
      polymerase chain reaction, Western blot analysis, and confocal immunofluorescence
      microscopy. Functional changes in the CFTR and ENaC proteins were assessed by
      measuring transepithelial resistance (TER) using a voltmeter combined with ion
      channel modulators. RESULTS: Rhinovirus infection increased expression of CFTR,
      alpha-ENaC, beta-ENaC, and gamma-ENaC messenger RNA (mRNA) and protein compared
      with controls (P < .05 each) and increased the expression of all 4 proteins on
      confocal immunofluorescence microscopy. Treatment of cells with the ENaC blocker
      amiloride and the CFTR activator forskolin increased TER in RV-infected cells,
      whereas forskolin decreased TER in uninfected cells. The CFTR inhibitor NPPB,
      however, blocked CFTR more in RV-infected than in noninfected cells. CONCLUSIONS:
      Rhinovirus increased the expression of CFTR and appeared to alter its function.
      In contrast, ENaC expression and function were increased by RV infection.
      Therefore, RV infection may impair mucociliary transport of nasal epithelium by
      these alterations.

PMID- 22374204
TI  - Characterization of respiratory deposition of fluticasone-salmeterol
      hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic
      patients.
AB  - BACKGROUND: Fixed combination fluticasone-salmeterol is the most used anti
      inflammatory asthma treatment in North America, yet no studies report the actual
      respiratory tract dose or the distribution of drug within the lungs. Inflammation
      due to asthma affects all airways of the lungs, both large and small. Inhaled
      steroid delivery to airways results from a range of drug particle sizes, with
      emphasis on smaller drug particles capable of reaching the peripheral airways.
      Previous studies suggested that smaller drug particles increase pulmonary
      deposition and decrease oropharyngeal deposition. OBJECTIVES: To characterize the
      dose of fluticasone-salmeterol hydrofluoroalkane-134a (HFA) (particle size, 2.7
      MUm) delivered to asthmatic patients and examine the drug distribution within the
      lungs. The results were compared with the inhalation delivery of HFA
      beclomethasone (particle size, 0.7 MUm). METHODS: A crossover study was conducted
      in asthmatic patients with commercial formulations of fluticasone-salmeterol and
      HFA beclomethasone radiolabeled with technetium Tc 99m. Deposition was measured
      using single-photon emission computed tomography/computed tomography gamma
      scintigraphy. RESULTS: Two-dimensional planar image analysis indicated that 58%
      of the HFA beclomethasone and 16% of the fluticasone-salmeterol HFA were
      deposited in the patient's lungs. The oropharyngeal cavity and gut analyses
      indicated that 77% of the fluticasone-salmeterol HFA was deposited in the
      oropharynx compared with 35% of the HFA beclomethasone. CONCLUSIONS: The
      decreased peripheral airway deposition and increased oropharyngeal deposition of
      fluticasone-salmeterol HFA was a result of its larger particle size. The smaller
      particle size of HFA beclomethasone allowed a greater proportion of lung
      deposition with a concomitant decrease in oropharyngeal deposition.

PMID- 22374205
TI  - How's my dosing? A one-step, math-free guide for comparing your clinic's
      maintenance immunotherapy doses to current practice parameter recommendations.
AB  - BACKGROUND: Immunotherapy dose recommendations for allergens specified in
      practice parameter updates have varied from version to version, and no convenient
      methods are available to incorporate dose changes or targets into maintenance
      vial formulations for patients. OBJECTIVES: To compare the allergen immunotherapy
      dose recommendations published between 2003-2011, and to provide math-free dosing
      tables that translate dose targets for single or multiple extracts into
      maintenance vial compositions. METHODS: Dose recommendations obtained from
      immunotherapy practice parameters published in 2003, 2007 and 2011, plus a
      worksheet created in 2004, were tabulated and compared. Conversion tables were
      created based on the fixed mathematical relationships between extract concentrate
      strengths and maintenance immunotherapy dose targets. Considerations of stock
      mixes, glycerin levels, and allergen compatibilities were applied using two
      examples of common extract formulations. RESULTS: Changes to immunotherapy dose
      ranges for standardized extracts included adjustment of upper limits (short
      ragweed), lower limits (pasture grasses), or both (cat, dust mites, Bermuda
      grass). Dose ranges for non-standardized products have also been modified over
      time. Conversion tables specified the extract concentrate volumes or percentages
      required to deliver minimum, midrange and maximum recommended doses with 0.5 mL
      injection volumes. CONCLUSIONS: These dosing guides, used in conjunction with
      cross-reactivity, compatibility and glycerin tolerance information, provide
      clinicians with a convenient and systematic method for determining the numbers
      and strengths of extracts that can be combined into treatment vials at various
      dose levels, and can facilitate optimization of maintenance immunotherapy
      mixtures for patients exhibiting a wide range of allergen sensitivities and
      specificities.

PMID- 22374206
TI  - Genetic variation and the risk of asthma: does it drive the differences in asthma
      prevalence among ethnic groups in North America?

PMID- 22374207
TI  - Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin.

PMID- 22374208
TI  - Anaphylactic shock due to SonoVue.

PMID- 22374209
TI  - Intraoperative anaphylaxis induced by the gelatin component of thrombin-soaked
      gelfoam in a pediatric patient.

PMID- 22374210
TI  - Ranitidine-induced anaphylaxis with detection of serum specific IgE to ranitidine
      and human serum albumin conjugates.

PMID- 22374211
TI  - Association of microbial IgE sensitizations with asthma in young children with
      atopic dermatitis.

PMID- 22374212
TI  - Allergen of the month--salt cedar.

PMID- 22374213
TI  - Current world literature.

PMID- 22374215
TI  - Stereoselective synthesis of bio-hybrid amphiphiles of coumarin derivatives by
      Ugi-Mannich triazole randomization using copper catalyzed alkyne azide click
      chemistry.
AB  - An efficient synthesis of ester-triazole-amide amphiphiles of coumarin
      derivatives by triazole randomization based on click approach is described.
      Twenty-five small peptide azides were synthesized using Ugi or alternate Mannich
      type multi-component reactions. The new azides were then used for the triazole
      randomization of alkyne functionalized coumarin ester under CuAAC conditions.
      Sixty-five new peptide bio-hybrids are obtained in near quantitative yield with
      high regio and stereoselectivity.

PMID- 22374216
TI  - A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with
      improved metabolic stability.
AB  - Following the previous SAR of a novel dihydropyrimidinone scaffold as HIV-1
      replication inhibitors a detailed study directed towards optimizing the metabolic
      stability of the ester functional group in the dihydropyrimidinone (DHPM)
      scaffold is described. Replacement of the ester moiety by thiazole ring
      significantly improved the metabolic stability while retaining antiviral activity
      against HIV-1 replication. These novel and potent DHPMs with bioisosteres could
      serve as advanced leads for further optimization.

PMID- 22374217
TI  - Pyridyl aminothiazoles as potent inhibitors of Chk1 with slow dissociation rates.
AB  - Pyridyl aminothiazoles comprise a novel class of ATP-competitive Chk1 inhibitors
      with excellent inhibitory potential. Modification of the core with
      ethylenediamine amides provides compounds with low picomolar potency and very
      high residence times. Investigation of binding parameters of such compounds using
      X-ray crystallography and molecular dynamics simulations revealed multiple
      hydrogen bonds to the enzyme backbone as well as stabilization of the conserved
      water molecules network in the hydrophobic binding region.

PMID- 22374219
TI  - Identification of a null allele in genetic tests for bovine leukocyte adhesion
      deficiency in Pakistani Bos indicus * Bos taurus cattle.
AB  - Two clinically healthy mature Pakistani Bos indicus * Bos taurus cattle were
      genotyped as homozygous affected for the lethal immunodeficiency disorder bovine
      leukocyte adhesion deficiency (BLAD) using previously described PCR-RFLP based
      DNA tests which was confirmed by sequencing. Sequencing of Bos taurus and B.
      indicus * B. taurus genomic DNA surrounding the disease causing mutation (c.383A
      > G) in the ITGB2 gene identified numerous variations in exonic and intronic
      regions within and between species, including substantial variation in primer
      annealing sites for three PCR-RFLP tests for one of the B. indicus allelic
      variants. These variations in the primer annealing sites resulted in a null
      allele in the DNA tests causing the misdiagnosis of some heterozygous B. taurus *
      B. indicus cattle to be classified as homozygous affected. New primers were
      designed and a modified test was developed which simultaneously identified the
      disease mutation and the Pakistani B. indicus allelic variant associated with the
      null allele in the previous test.

PMID- 22374220
TI  - Where should we go?

PMID- 22374218
TI  - Regulation of zebrafish heart regeneration by miR-133.
AB  - Zebrafish regenerate cardiac muscle after severe injuries through the activation
      and proliferation of spared cardiomyocytes. Little is known about factors that
      control these events. Here we investigated the extent to which miRNAs regulate
      zebrafish heart regeneration. Microarray analysis identified many miRNAs with
      increased or reduced levels during regeneration. miR-133, a miRNA with known
      roles in cardiac development and disease, showed diminished expression during
      regeneration. Induced transgenic elevation of miR-133 levels after injury
      inhibited myocardial regeneration, while transgenic miR-133 depletion enhanced
      cardiomyocyte proliferation. Expression analyses indicated that cell cycle
      factors mps1, cdc37, and PA2G4, and cell junction components cx43 and cldn5, are
      miR-133 targets during regeneration. Using pharmacological inhibition and EGFP
      sensor interaction studies, we found that cx43 is a new miR-133 target and
      regeneration gene. Our results reveal dynamic regulation of miRNAs during heart
      regeneration, and indicate that miR-133 restricts injury-induced cardiomyocyte
      proliferation.

PMID- 22374221
TI  - A method for topological analysis of high nuclearity coordination clusters and
      its application to Mn coordination compounds.
AB  - A novel method for the topological description of high nuclearity coordination
      clusters (CCs) was improved and applied to all compounds containing only
      manganese as a metal center, the data on which are collected in the CCDC (CCDC
      5.33 Nov. 2011). Using the TOPOS program package that supports this method, we
      identified 539 CCs with five or more Mn centers adopting 159 topologically
      different graphs. In the present database all the Mn CCs are collected and
      illustrated in such a way that can be searched by cluster topological symbol and
      nuclearity, compound name and Refcode. The main principles for such an analysis
      are described herein as well as useful applications of this method.

PMID- 22374222
TI  - Increased apoptotic neuronal cell death and cognitive impairment at early phase
      after traumatic brain injury in aged rats.
AB  - Progressive age-associated increases in cerebral dysfunction have been shown to
      occur following traumatic brain injury (TBI). Moreover, levels of neuronal
      mitochondrial antioxidant enzymes in the aged brain are reduced, resulting in
      free radical-induced cell death. It was hypothesized that cognitive impairment
      after TBI in the aged progresses to a greater degree than in younger individuals,
      and that damage involves neuronal degeneration and death by free radicals. In
      this study, we investigated the effects of free radicals on neuronal
      degeneration, cell death, and cognitive impairment in 10-week-old (young group)
      and 24-month-old rats (aged group) subjected to TBI. Young and aged rats received
      TBI with a pneumatic controlled injury device. At 1, 3 and 7 days after TBI,
      immunohistochemistry, lipid peroxidation and behavioral studies were performed.
      At 1, 3 and 7 days post-TBI, the number of 8-hydroxy-2'-deoxyguanosine-, 4
      hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and the levels
      of malondialdehyde around the damaged area after TBI significantly increased in
      the aged group when compared with the young group (P < 0.05). In addition, the
      majority of ssDNA-positive cells in both groups co-localized with neuronal cells
      around the damaged area. There was a significant decrease in the number of
      surviving neurons and an increase in cognitive impairment after TBI in the aged
      group when compared with the young group (P < 0.05). These results indicate that
      following TBI, high levels of free radicals are produced in the aged rat brain,
      which induces neuronal degeneration and apoptotic cell death around the damaged
      area, resulting in cognitive impairment.

PMID- 22374223
TI  - VGLUT3-immunoreactive afferents of the lateral septum: ultrastructural evidence
      for a modulatory role of glutamate.
AB  - Through its extensive connections with various brain regions, the lateral septum
      (LS) participates in the processing of cognitive, emotional and autonomic
      information. It is decisively involved in the generation of behavioral responses
      according to environmental demands. Modulatory afferents reaching the LS from the
      brain stem (e.g. dopaminergic, serotonergic) play a role in the adjustment of
      these behavioral responses. Recently, a population of vesicular glutamate
      transporter 3-immunoreactive (VGLUT3-ir) fibers forming prominent pericellular
      basket-like structures (PBLS) was described in the rat LS. These VGLUT3-ir PBLS
      are distributed in a layer-like pattern, which is very typical for modulatory
      afferents of the LS. There is meanwhile broad evidence that glutamate can act as
      a modulatory or co-transmitter and that those neurons, which make use of this
      transmission mode, primarily express VGLUT3. Thus, the VGLUT3-ir fibers within
      the LS could also display features typical for non-canonical glutamatergic
      transmission. Employing pre-embedding electron microscopy for VGLUT3 in rats, we
      show now that the VGLUT3-ir fibers outlining LS neurons represent axonal
      terminals, which primarily form symmetric synapses with somata and proximal
      dendrites of their target neurons. Occasionally, we also found VGLUT3-ir
      terminals that make canonical asymmetric synapses on distal dendrites and spines.
      Thus, VGLUT3-ir boutons in the LS form two different, disproportionate,
      populations of synaptic contacts with their target neurons. The larger one of
      them is indicative of employing glutamate as a modulatory transmitter.

PMID- 22374225
TI  - Of animals and objects: men's implicit dehumanization of women and likelihood of
      sexual aggression.
AB  - Although dehumanizing women and male sexual aggression are theoretically aligned,
      the present research provides the first direct support for this assumption, using
      the Implicit Association Test to assess two forms of female dehumanization:
      animalization and objectification. In Study 1, men who automatically associated
      women more than men with primitive constructs (e.g., animals, instinct, nature)
      were more willing to rape and sexually harass women, and to report negative
      attitudes toward female rape victims. In Study 2, men who automatically
      associated women with animals (e.g., animals, paw, snout) more than with humans
      scored higher on a rape-behavioral analogue, as well as rape proclivity.
      Automatically objectifying women by associating them with objects, tools, and
      things was also positively correlated with men's rape proclivity. In concert, the
      research demonstrates that men who implicitly dehumanize women (as either animals
      or objects) are also likely to sexually victimize them.

PMID- 22374224
TI  - A neuroanatomical model of prefrontal inhibitory modulation of memory retrieval.
AB  - Memory of past experience is essential for guiding goal-related behavior. Being
      able to control accessibility of memory through modulation of retrieval enables
      humans to flexibly adapt to their environment. Understanding the specific neural
      pathways of how this control is achieved has largely eluded cognitive
      neuroscience. Accordingly, in the current paper I review literature that examines
      the overt control over retrieval in order to reduce accessibility. I first
      introduce three hypotheses of inhibition of retrieval. These hypotheses involve:
      (i) attending to other stimuli as a form of diversionary attention, (ii)
      inhibiting the specific individual neural representation of the memory, and (iii)
      inhibiting the hippocampus and retrieval process more generally to prevent
      reactivation of the representation. I then analyze literature taken from the
      White Bear Suppression, Directed Forgetting and Think/No-Think tasks to provide
      evidence for these hypotheses. Finally, a neuroanatomical model is developed to
      indicate three pathways from PFC to the hippocampal complex that support
      inhibition of memory retrieval. Describing these neural pathways increases our
      understanding of control over memory in general.

PMID- 22374226
TI  - Spatial horizons in amplitude and frequency modulation atomic force microscopy.
AB  - In dynamic atomic force microscopy (AFM) the cantilever is vibrated and its
      dynamics are monitored to probe the sample with nanoscale and atomic resolution.
      Amplitude and frequency modulation atomic force microscopy (AM-AFM and FM-AFM)
      have established themselves as the most powerful methods in the field.
      Nevertheless, it is still debatable whether one or the other technique is
      preferred in a given medium or experiment. Here, we quantitatively establish and
      compare the limitations in resolution of both techniques by introducing the
      concept of spatial horizon (SH) and quantifying it. The SH is the limiting
      spatial boundary beyond which collective atomic interactions do not affect the
      detection parameters of a given feedback system. We show that while an FM-AFM
      feedback can resolve a single atom or atomic defect where an AM feedback might
      fail, relative contrast is in fact equivalent for both feedback systems. That is,
      if the AM feedback could detect sufficiently small amplitude shifts and there was
      no noise, the detection of single atoms or atomic defects would be equivalent in
      AM-AFM and FM-AFM.

PMID- 22374227
TI  - Tobacco use and substance use disorders as predictors of postoperative weight
      loss 2 years after bariatric surgery.
AB  - Although evaluations of tobacco and substance use disorders (SUDs) are required
      before bariatric surgery, the impact of these factors on postsurgical outcomes is
      unclear. This study describes (1) the prevalence of tobacco and SUDs in 61
      veterans undergoing bariatric surgery, (2) associations between presurgical
      tobacco use and postsurgical weight loss, and (3) relationships between
      presurgical SUDs and postsurgical weight loss. Height, weight, tobacco, and SUDs
      were assessed from medical charts at presurgery and 6, 12, and 24 months
      postsurgery. Thirty-three patients (55%) were former or recent tobacco users;
      eight (13%) had history of SUDs. All patients who quit smoking within 6 months
      before surgery resumed after surgery, which was associated with increased weight
      loss at 6 and 12 months. Presurgical SUDs were related to marginally worse weight
      loss at 12 and 24 months. Bariatric surgery candidates with history of smoking
      and/or SUDs might benefit from additional services to improve postsurgical
      outcomes.

PMID- 22374228
TI  - Partial deletion of rng (RNase G)-enhanced homoethanol fermentation of xylose by
      the non-transgenic Escherichia coli RM10.
AB  - Previously, a native homoethanol pathway was engineered in Escherichia coli B by
      deletions of competing pathway genes and anaerobic expression of pyruvate
      dehydrogenase (PDH encoded by aceEF-lpd). The resulting ethanol pathway involves
      glycolysis, PDH, and alcohol dehydrogenase (AdhE). The E. coli B-derived
      ethanologenic strain SZ420 was then further improved for ethanol tolerance (up to
      40 g l(-1) ethanol) through adaptive evolution. However, the resulting ethanol
      tolerant mutant, SZ470, was still unable to complete fermentation of 75 g l(-1)
      xylose, even though the theoretical maximum ethanol titer would have been less
      than 40 g l(-1) should the fermentation have reached completion. In this study,
      the cra (encoding for a catabolite repressor activator) and the HSR2 region of
      rng (encoding for RNase G) were deleted from SZ470 in order to improve xylose
      fermentation. Deletion of the HSR2 domain resulted in significantly increased
      mRNA levels (47-fold to 409-fold) of multiple glycolytic genes (pgi, tpiA, gapA,
      eno), as well as the engineered ethanol pathway genes (aceEF-lpd, adhE) and the
      transcriptional regulator Fnr (fnr). The higher adhE mRNA level resulted in
      increased AdhE activity (>twofold). Although not measured, the increase of other
      mRNAs might also enhance expressions of their encoding proteins. The increased
      enzymes would then enable the resulting strain, RM10, to achieve increased cell
      growth and complete fermentation of 75 g l(-1) xylose with an 84% improved
      ethanol titer (35 g l(-1)), compared to that (19 g l(-1)) obtained by the parent,
      SZ470. However, deletion of cra resulted in a negative impact on cell growth and
      xylose fermentation, suggesting that Cra is important for long-term fermentative
      cell growth.

PMID- 22374229
TI  - Biocatalytic conversion of aloeresin A to aloesin.
AB  - Leaf exudates from Aloe species, such as the Southern African Aloe ferox, are
      used in traditional medicines for both humans and livestock. This includes
      aloesin, a skin bleaching product that inhibits the synthesis of melanin.
      Aloesin, (a C-glycoside-5-methylchromone) can be released from aloeresin A, an
      ester of aloesin, through hydrolysis. The objective of the current study was to
      identify an enzymatic hydrolysis method for converting aloeresin A to aloesin,
      resulting in increased concentrations of aloesin in the aloe bitters extract.
      More than 70 commercially available hydrolytic enzymes were screened for the
      conversion of aloeresin A. An esterase (ESL001-02) from Diversa, a lipase
      (Novozym 388) and a protease (Aspergillus oryzae) preparation were identified
      during screening as being capable of providing conversion of pure aloeresin A,
      with the protease giving the best conversion (~100%). It was found that a
      contaminating enzyme in Novo 388 was responsible for the conversion of aloeresin
      A to aloesin. This contaminating enzyme, possibly a protease, was able to give
      almost complete conversion using crude aloe bitters extract, doubling the
      concentration of aloesin in aloe bitters extract via the hydrolysis of aloeresin
      A.

PMID- 22374230
TI  - External validation of simulation-based assessments with other performance
      measures of third-year anesthesiology residents.
AB  - INTRODUCTION: There has been interest in the use of high-fidelity medical
      simulation to evaluate performance. We hypothesized that technical and
      nontechnical performance in the simulated environment is related to other various
      criterion measures, providing evidence to support the validity of the scores from
      the performance-based assessment. METHODS: Twelve third-year anesthesia residents
      participated in a series of 6 short 5-minute scenarios and 1 longer 30-minute
      scenario. The short scenarios measured technical skills, whereas the longer one
      focused on nontechnical skills. Two independent raters scored subjects using
      analytic and holistic ratings. Short scenarios involved acute hemorrhage, blocked
      endotracheal tube, bronchospasm, hyperkalemia, tension pneumothorax, and unstable
      ventricular tachycardia. The long scenario concerned management of myocardial
      ischemia/infarction leading to cardiac arrest. Scores from the simulations were
      correlated with (a) rankings generated from an Internet-based global ranking
      instrument that categorized residents based on overall clinical ability and (b)
      residency board scores. RESULTS: There were moderate correlations between various
      participant scores from the simulation-based assessment and aggregate rankings
      based on the global ranking instrument and residency examination scores.
      CONCLUSIONS: The associations between simulator performance, both for technical
      and nontechnical skills, and other markers of ability provide some evidence to
      support the validity of simulation-based assessment scores. Replication studies
      with larger numbers of residents are warranted.

PMID- 22374231
TI  - Early use of simulation in medical education.
AB  - An oft-cited belief that, until recently, simulators used in education of health
      care professionals were simple models is wrong. Hundreds of years ago and, in one
      instance, thousands of years ago, intricate models were used to help teach
      anatomy and physiology and in training in obstetrics and many surgical
      disciplines. Simulators were used to learn skills before performing them on
      patients and in high-stakes assessment.The newest technologies were often used in
      simulators to improve fidelity. In the 18th century, obstetric simulators could
      leak amniotic fluid, and blood were used to train midwives and obstetricians to
      recognize and manage complications of childbirth. Italy was the major source of
      simulators early in the 18th century, but in the 19th century, dominance in
      clinical simulation moved to France, Britain, and then Germany. In comparison,
      much of the 20th century was a "dark age" for simulation.

PMID- 22374232
TI  - Study of feasibility and acceptability of subcutaneous implantable ports (SIPs)
      in cancer patients.
AB  - OBJECTIVE: To assess the feasibility and complication rate associated with
      Subcutaneous Implantable Ports (SIPs) in pediatric cancer patients. METHODS:
      Ninety nine patients underwent chemo port insertion between January2003 to May
      2011 with variety of neoplastic diseases. Data was collected with regards to
      underlying condition, duration the catheter was in situ and complications during
      insertion, accessing and removal. Chemoport was inserted either at diagnosis or
      once optimal conditions were achieved. Ports were placed in internal jugular vein
      (IJV) or subclavian vein (SCV) under general or local anesthesia under strict
      aseptic conditions in theatre. RESULTS: A total of 100 ports were placed in 99
      patients. The mean duration of the implantable ports was 393 days (range 30
      1300). In 49 cases (49%), ports were removed electively, 15 cases (15%) died with
      port in situ and 36 cases (36%) still have port in situ and receiving
      chemotherapy without any complications. Complications observed were suspected
      infection (4%), port fracture (4%), thrombosis of catheter (1%) and blockage
      (1%). CONCLUSIONS: The use of ports is safe and feasible in Pediatric Oncology
      patients if strict asepsis guidelines are followed.

PMID- 22374233
TI  - Multifocal Tuberculous osteomyelitis: possible inherited interferon gamma axis
      defect.
AB  - Multifocal Tuberculous (TB) osteomyelitis is an extremely rare entity in
      immunocompetent individuals. The authors report a 19-mo-old girl with multifocal
      TB osteomyelitis which resolved completely following institution of four drug
      antituberculous treatment for 1 y and detailed immunological evaluation was found
      to be normal but as the response of interferon gamma (IFN gamma) in terms of
      production of IL12p40 was severely impaired, she is suggested to have a possible
      defect in the interferon gamma axis even though the exact defect in the pathway
      could not be delineated. This case report reiterates the need for detailed
      immunological evaluation in children presenting with multifocal TB osteomyelitis.

PMID- 22374234
TI  - Clinical profile of scrub typhus in children.
AB  - OBJECTIVE: To study the clinical profile and outcome of scrub typhus cases
      admitted in an urban referral centre. METHODS: This descriptive study describes
      the clinical profile of 67 children with scrub typhus, who were admitted in an
      urban referral centre(ICH & HC,Chennai) during the period between October 2010
      and March 2011.The diagnosis was confirmed by IgM ELISA. RESULTS: All children
      presented with fever. Eschar and rash were present in 46% and 35% cases,
      respectively. Cough, vomiting, altered sensorium and oliguria were present in
      73%,59%,58% and 43%, respectively. Hepatosplenomegaly and pallor were the
      commonest findings encountered in more than 80% children. Other findings were
      edema, lymphadenopathy and icterus.Thrombocytopenia, elevated liver enzymes and
      leukocytosis were seen in 77%, 64% and 49% cases, respectively. Pleural effusion,
      ascites, shock and respiratory failure were seen in 61%, 47%,45%,34% cases,
      respectively. Acute renal failure, hepatic failure, multiorgan dysfunction
      syndrome (MODS), meningoencephalitis and acute respiratory distress
      syndrome(ARDS) were seen in 10%,10%,7%,6% and 4% cases, respectively. Doxycycline
      and azithromycin were the antibiotics used. The overall mortality rate was
      11.94%. Causes of death were shock, ARDS, acute renal failure(ARF), MODS and
      disseminated intravascular coagulation(DIVC). CONCLUSIONS: When a child presents
      with acute febrile illness, maculopapular or erythematous rash,
      hepatosplenomegaly, lymphadenopathy, thrombocytopenia and features suggestive of
      capillary leak, diagnosis of Scrub typhus must be considered and the child should
      be started on empirical therapy with doxycycline or azithromycin which is life
      saving.

PMID- 22374235
TI  - Identification of novel inter-genotypic recombinants of human hepatitis B viruses
      by large-scale phylogenetic analysis.
AB  - Recombination plays an important role in the evolutionary history of Hepatitis B
      virus (HBV). We performed a phylogenetic analysis of 3403 full-length HBV genome
      sequences isolated from humans to define the genotype. The genome sequences were
      divided into 13 sub-datasets, each approximately 250 bp in length. Genotype
      designations obtained from the sub-datasets that differed from the genotype
      defined by the whole genome were assigned as putative recombinants. Our results
      showed that 3379 out of 3403 sequences belonged to the previously described and
      putative genotypes A to J respectively, with 315 sequences defined in this
      analysis. The remaining 24 viruses had sequence divergence of less than 8% with
      both genotypes B and C and were provisionally assigned genotype "BC". 1047 out of
      3403 sequences were identified to be putative recombinants, of which 72 were
      identified to be novel recombinants. Notably, all viruses of the herein described
      genotype "BC" were identified to be B/C recombinants.

PMID- 22374236
TI  - Integrase-independent HIV-1 infection is augmented under conditions of DNA damage
      and produces a viral reservoir.
AB  - HIV-1 possesses a viral protein, integrase (IN), which is necessary for its
      efficient integration in target cells. However, it has been reported that an IN
      defective HIV strain is still capable of integration. Here, we assessed the
      ability of wild type (WT) HIV-1 to establish infection in the presence of IN
      inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells
      infected with WT HIV which was identical to cells infected with IN-deficient HIV,
      D64A. Furthermore, the IN-independent integration could be enhanced by the
      pretreatment of cells with DNA-damaging agents suggesting that integration is
      mediated by a DNA repair system. Moreover, significantly faster viral replication
      kinetics with augmented viral DNA integration was observed after infection in
      irradiated cells treated with IN inhibitor compared to nonirradiated cells.
      Altogether, our results suggest that HIV DNA has integration potential in the
      presence of an IN inhibitor and may serve as a virus reservoir.

PMID- 22374237
TI  - An improved authentication scheme for telecare medicine information systems.
AB  - The telecare medicine information system enables or supports health-care delivery
      services. In order to safeguard patients' privacy, such as telephone number,
      medical record number, health information, etc., a secure authentication scheme
      will thus be in demand. Recently, Wu et al. proposed a smart card based password
      authentication scheme for the telecare medicine information system. Later, He et
      al. pointed out that Wu et al.'s scheme could not resist impersonation attacks
      and insider attacks, and then presented a new scheme. In this paper, we show that
      both of them fail to achieve two-factor authentication as smart card based
      password authentication schemes should achieve. We also propose an improved
      authentication scheme for the telecare medicine information system, and
      demonstrate that the improved one satisfies the security requirements of two
      factor authentication and is also efficient.

PMID- 22374238
TI  - Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene
      polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis.
AB  - Results from studies on the association of PTPN22 C1858T polymorphism with AITD
      risk are conflicting, we thereby perform this meta-analysis to derive a more
      precise effect on this possible association.  Two investigators independently
      searched the PubMed, Embase, Wanfang and CNKI (China National Knowledge
      Infrastructure) databases.  A total of 11 studies with 3764 AITDs cases and 3328
      controls were finally identified.  Statistically significant association was
      observed between PTPN22 C1858T polymorphism and AITD risk based on all studies
      (TT vs. CC, OR=2.18, 95%CI=1.31~3.62; TC vs. CC, OR=1.50, 95%CI=1.29~1.73; TT/TC
      vs. CC, OR=1.41, 95%CI=1.12~1.78; TT vs. TC/CC, OR=2.00, 95%CI=1.21~3.33).  The
      results of subgroup analysis showed that: (1) regarding ethnic diversity, the
      variant genotypes TT/TC of C1858T were associated with a significantly increased
      AITD risk in Caucasians (TT/TC vs. CC, OR=1.41, 95%CI=1.09~1.83) (2) regarding
      different countries, the statistically significantly association was observed in
      UK (TC vs. CC, OR=1.64, 95%CI=1.36~1.98; TT/TC vs. CC, OR=1.65, 95%CI=1.37~1.98)
      and other countries (including South Tunisia, Russia, Polish, Japanese) (TT vs.
      CC, OR=3.65, 95%CI=1.43~9.33; TT vs. TC/CC, OR=3.41, 95%CI=1.34~8.65).  (3)
      regarding the subtypes of AITDs, patients with Graves' disease (GD) had a
      significant higher degree of C1858T polymorphism (TT vs. CC, OR=2.35,
      95%CI=1.36~4.05; TC vs. CC, OR=1.46, 95%CI=1.12~1.89; TT/TC vs. CC, OR=1.54,
      95%CI=1.33~1.80; TT vs. TC/CC, OR=2.16, 95%CI=1.25~3.72), while no association
      was observed in patients with Hashimoto's thyroiditis (HT).  No publication bias
      was observed.  Our results demonstrated that PTPN22 C1858T polymorphism was
      associated with AITD risk, especially in Caucasians.

PMID- 22374239
TI  - Preoperative insulin secretion ability and pancreatic parenchymal thickness as
      useful parameters for predicting postoperative insulin secretion in patients
      undergoing pancreaticoduodenectomy.
AB  - Periampullary malignant neoplasms have been increasing in Japan, mainly in
      response to an increase in the incidences of pancreatic cancer, and glucose
      intolerance due to deterioration of insulin secretion is an important problem. 
      We investigated preoperative parameters to predict postoperative insulin
      secretion and the need for insulin therapy in patients undergoing
      pancreaticoduodenectomy (PD).  Thirty-six patients with malignant neoplasms of
      periampullary lesions were enrolled.  Preoperative pancreatic parenchymal
      thickness was evaluated by computed tomography.  Insulin secretion and glucose
      tolerance were evaluated by a 75-g oral glucose tolerance test and an intravenous
      glucagon loading test.  The relationships between postoperative insulin secretion
      and preoperative parameters and the cut-off values for predicting the need for
      postoperative insulin therapy for glycemic control were investigated.  Pancreatic
      parenchymal thickness and other preoperative parameters, including the increment
      of serum C-peptide (Delta C-peptide), fasting plasma C-peptide (F-CPR),
      insulinogenic index (I.I.) and fasting plasma glucose (FPG), were significantly
      associated with postoperative insulin secretion.  Multiple regression analyses
      revealed that preoperative Delta C-peptide or F-CPR was the most significant
      determinant of postoperative insulin secretion, followed by pancreatic
      parenchymal thickness.  In the receiver operating characteristic curve, the best
      preoperative cut-off values for predicting the need for postoperative insulin
      therapy were a Delta C-peptide of 0.65 ng/mL, a F-CPR of 0.85 ng/mL and a
      pancreatic parenchymal thickness of 6.0 mm.  Both preoperative insulin secretion
      and pancreatic parenchymal thickness effectively predict postoperative insulin
      secretion and identify subjects who need postoperative insulin therapy for
      glycemic control.

PMID- 22374240
TI  - Relationship between prognosis of papillary thyroid carcinoma patient and age: a
      retrospective single-institution study.
AB  - Age is an important prognostic factor in papillary thyroid carcinoma (PTC).  In
      this study, we investigated the difference in prognosis of 7 subsets of PTC
      patients without distant metastasis at presentation or a history of radiation
      exposure (20 years or younger, 21-30 years, 31-40 years, 41-50 years, 51-60
      years, 61-70 years, and older than 70 years).  The lymph node recurrence rate was
      high in patients 20 years or younger and those older than 60 years.  Distant
      recurrence and carcinoma death rates significantly elevated in patients older
      than 60 years.  The incidence of significant extrathyroid extension markedly
      increased with age, although that of large node metastasis or extranodal tumor
      extension did not differ much among the 7 subsets.  With the Kaplan-Meier method,
      lymph node recurrence rate was poor in patients 20 years or younger and in those
      older than 60 years.  Poor distant recurrence-free and cause specific survivals
      of patients older than 60 years were identified in the series of PTC patients
      with and without these aggressive features.  It is therefore suggested that 1)
      Lymph node recurrence rate was high in patients 20 years or younger and those
      older than 60 years and 2) prognosis, including distant recurrence-free survival
      and cause-specific survival, of patients older than 60 years was poor regardless
      of clinicopathological features of PTC at initial surgery.

PMID- 22374241
TI  - Heterolytic dihydrogen activation by B(C6F5)3 and carbonyl compounds.
AB  - Aromatic carbonyl compounds in combination with B(C(6)F(5))(3) are able to
      activate H(2) heterolytically. The reactivity of the carbonyl-B(C(6)F(5))(3)
      adduct is initiated by its thermal dissociation into components. After H(2)
      addition, aromatic carbonyl compounds convert into aryl-substituted methanes or
      alcohols.

PMID- 22374243
TI  - In vitro generation of functional insulin-producing cells from lipoaspirated
      human adipose tissue-derived stem cells.
AB  - BACKGROUND AND AIMS: Tissue engineering strategy has been considered as an
      alternative treatment for diabetes mellitus due to lack of permanent
      pharmaceutical treatment and islet donors for transplantation. Various cell lines
      have been used to generate functional insulin-producing cells (IPCs) including
      progenitor pancreatic cell lines, embryonic stem cells (ESCs), umbilical cord
      blood stem cells (UCB-SCs), adult bone marrow stem cells (BMSCs), and adipose
      tissue-derived stem cells (ADSCs). METHODS: Human ADSCs from lipoaspirated
      abdominal fat tissue was differentiated into IPCs following a two-step induction
      protocol based on a combination of alternating high and low glucose,
      nicotinamide, activin A and glucagon-like peptide 1 (GLP-1) for a duration of 3
      weeks. During differentiation, histomorphological changes of the stem cells
      towards pancreatic beta-islet characteristics were observed via light microscope
      and transmission electron microscope (TEM). Dithizone (DTZ) staining, which is
      selective towards IPCs, was used to stain the new islet-like cells. Production of
      insulin hormone by the cells was analyzed via enzyme-linked immunosorbent assay
      (ELISA), whereas its hormonal regulation was tested via a glucose challenge test.
      RESULTS: Histomorphological changes of the differentiated cells were noted to
      resemble pancreatic beta-cells, whereas DTZ staining positively stained the
      cells. The differentiated cells significantly produced human insulin as compared
      to the undifferentiated ADSCs, and its production was increased with an increase
      of glucose concentration in the culture medium. CONCLUSIONS: These initial data
      indicate that human lipoaspirated ADSCs have the potential to differentiate into
      functional IPCs, and could be used as a therapy to treat diabetes mellitus in the
      future.

PMID- 22374244
TI  - ERCC1 gene +262A/C polymorphism associated with risk of gastric cardiac
      adenocarcinoma in nonsmokers.
AB  - BACKGROUND AND AIMS: Polymorphisms in DNA repair gene may alter an individual's
      DNA repair capacity and be associated with the risk of various cancers. This
      study was designed to investigate whether ERCC1 +262A/C and XPF -357A/C
      polymorphisms affect individual susceptibility to esophageal squamous cell
      carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). METHODS: In 389 ESCC
      patients vs. 778 healthy controls and 262 GCA patients vs. 524 healthy controls
      in a high incidence region of northern China, ERCC1 +262A/C polymorphism and XPF 
      357A/C polymorphism were genotyped by the method of polymerase chain reaction
      ligase detection reaction (PCR-LDR) and polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) analysis, respectively. RESULTS: Family
      history of upper gastrointestinal cancers (UGIC) may increase the risk of ESCC
      and GCA. Allelotype and genotype distributions of ERCC1 +262A/C and XPF -357A/C
      polymorphisms in ESCC and GCA patients were not significantly different from that
      in their respective controls (p >0.05). Compared with ERCC1 +262C/C genotype, A/A
      genotype decreased the risk of GCA in nonsmokers (age, gender and family history
      of UGIC adjusted odds ratio [OR] = 0.30, 95% confidence interval [CI] = 0.13
      0.70). Neither the A/C nor the C/C genotype was associated with the overall risk
      of ESCC and GCA when compared with the XPF -357A/A genotype. CONCLUSIONS: ERCC1
      +262A/A genotype may reduce the risk of GCA for nonsmokers. XPF -357A/C
      polymorphism was not associated with the risk of ESCC and GCA in a population of
      a high-incidence region in northern China.

PMID- 22374245
TI  - Alteration of telomere length and subtelomeric methylation in human endothelial
      cell under different levels of hypoxia.
AB  - BACKGROUND AND AIMS: Hypoxia-associated changes of telomeric structure in cell
      cultures have been analyzed mainly in cancer cells, stem cells, or cells
      transduced with vectors containing the telomerase gene, but not in somatic cells.
      The stability of telomere structure has been reported to be associated with
      subtelomeric methylation status. However, there are no reports of epigenetic
      alterations of telomeric regions of human somatic cells under hypoxia. This study
      aims at detecting and analyzing the subtelomeric methylation status in human
      somatic cells cultured under hypoxia. METHODS: Mean telomere length and
      telomerase activity of human umbilical vein endothelial cells (HUVECs) cultured
      in hypoxic conditions were measured. Subtelomeric methylation status of these
      cells was assessed by genomic Southern blot with telomere DNA probe using
      methylation-sensitive and -insensitive isoschizomers, MspI and HpaII. RESULTS:
      The telomerase activity in HUVECs correlated inversely with the oxygen
      concentration. Mild hypoxia (10 or 15% oxygen) increased the telomere lengths,
      whereas the telomere lengths did not appear to change when <1% O(2). The
      subtelomere of the shortest telomere range was methylated the most at 1% O(2).
      CONCLUSIONS: Subtelomeric hypermethylation of short telomeres at 1% O(2) compared
      to milder hypoxia implied that the subtelomeric hypermethylation may yield
      telomere stability and favor the cell survival of short telomere-bearing cells.

PMID- 22374246
TI  - Association between MTHFR C677T polymorphism and diabetic nephropathy in a
      Chinese population: appraisal of a recent meta-analysis.

PMID- 22374247
TI  - Distortion of beta-globin chain of hemoglobin alters the pathway of erythrocytic
      glucose metabolism through band 3 protein.
AB  - BACKGROUND AND AIMS: Band 3 is a transmembrane protein of erythrocytes and its
      cytosolic part regulates glucose metabolism to proceed along the pentose
      phosphate pathway (PPP) or glycolytic pathway by binding with the central cavity
      of the beta chain of deoxygenated hemoglobin and with some glycolytic enzymes
      competitively. In beta thalassemia major and hemoglobin (Hb)Ebeta thalassemia,
      beta chain is either absent or distorted and glucose metabolism may be disturbed.
      We estimated adenosine triphosphate (ATP), glucose 6-phosphate dehydrogenase
      (G6PD) and aldolase activity in oxygenated and deoxygenated state of erythrocytes
      of beta major, HbEbeta thalassemia and normal controls to understand the
      hypothesis that major glucose metabolism within the erythrocytes of these
      diseases may proceed through the PPP. METHODS: Fifty of each group of patients
      and 52 normal controls were included. Patients' blood was collected 1 month prior
      to blood transfusion. G6PD and aldolase were estimated using a commercial kit.
      ATP was measured by spectrophotometric method. RESULTS: Significantly low levels
      of erythrocytic ATP and higher levels of G6PD were found in two groups of
      patients. Aldolase level in deoxygenated hemolysate was significantly higher than
      oxygenated hemolysate in normal controls but no significant change was noticed in
      both types of thalassemic patients. CONCLUSIONS: In beta thalassemia major and
      HbEbeta thalassemia due to distortion of beta chain, binding of deoxygenated
      hemoglobin with band 3 is inhibited and thus traffic control of glycolytic
      pathway is disturbed and shifted towards PPP.

PMID- 22374248
TI  - Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer
      susceptibility in North India.
AB  - BACKGROUND AND AIMS: The importance of matrix metalloproteinases (MMPs) and their
      tissue inhibitors (TIMPs) in tumor progression is well documented. MMP2/TIMP2
      system has a significant impact on the development and progression of cancer and
      genetic polymorphisms in the promoters of MMP2 (-1306C/T, 735C/T) and TIMP2 (
      418G/A, -303C/T) are correlated with decreased enzyme activity. We sought to
      determine whether genetic polymorphisms in MMP2 and TIMP2 polymorphisms may be
      associated with varying risk of prostate cancer (PCa) in men in North India.
      METHODS: Genotyping was done by PCR-restriction fragment length polymorphism
      method in 190 histologically confirmed PCa patients and 200 unrelated, healthy,
      age-matched individuals of similar ethnicity. RESULTS: Patients with MMP2 (-1306)
      CT genotype as well as T allele were at higher risk of PCa (p = 0.018; OR = 1.68
      and p = 0.015; OR = 1.52). This effect was even more evident in the case of the T
      allele carrier (CT + TT) (p = 0.011; OR = 1.71). MMP2 (735) C>T, TIMP2 (-418) G>C
      and TIMP2 (-303) C>T polymorphism demonstrated no association. However, TIMP2 (
      418) GC was found to be involved in progression of PCa but not in initiation.
      Haplotype results demonstrated that MMP2 (1306T-735C) and TIMP2 (418G-303T) were
      associated with a 1.5- and 1.8-fold increased risk, respectively. CONCLUSIONS:
      Our data indicated that MMP2-1306C>T gene polymorphism contributes to PCa
      susceptibility. These findings suggested MMP2 variants as a predictor of PCa
      progression risk among North Indian men. We assume that analysis of these gene
      polymorphisms can help identify patient subgroups at high risk of poor disease
      outcome.

PMID- 22374249
TI  - Adiponectin level and gene variability are obesity and metabolic syndrome markers
      in a young population.
AB  - BACKGROUND AND AIMS: Human obesity is accepted as an important risk factor for
      development of MetS. Adiponectin is linked to central obesity and ADIPOQ variants
      are promising markers for understanding the genetic base of obesity-related
      disorders. We performed analyses of adiponectin concentrations and ADIPOQ
      variants and tested their associations with obesity and MetS in young subjects of
      Croatian origin. METHODS: Biochemical and anthropometric parameters of MetS were
      obtained for 149 unrelated subjects. Adiponectin levels were measured by ELISA
      assay. ADIPOQ -11391G>A and -11377C>G were genotyped by real-time PCR. RESULTS:
      BMI and WC, TG and GLUC showed inverse correlation, whereas HDL-C showed a
      positive correlation with adiponectin concentrations. For central obesity, we
      found association with -11377C>G and with -11391G>A polymorphisms. ADIPOQ 
      11377GG and -11391GA significantly increased the risk for the development of
      central obesity (OR 5.57 and OR 3.37, respectively). Significant association was
      found between -11391A, -11377G allele and haplotype and increased TG. -11377C>G
      and -11391G>A variant were significantly associated with the incidence of MetS.
      C>G mutation at position -11377 significantly increased the risk of MetS
      development (OR = 2.93). Compared with the -11391G homozygotes, carriers of the A
      allele had a significantly increased risk for the development of MetS (OR =
      3.15). The test of overall association showed a statistically significant
      correlation of MetS with -11377C>G and -11391G>A haplotypes (p = 0.008).
      CONCLUSIONS: Analysis of adiponectin concentration and ADIPOQ -11391G>A and 
      11377C>G gene variants may be clinically meaningful for estimation of MetS risk
      in a young population.

PMID- 22374250
TI  - 7-year follow up of intra-operative radiotherapy for early breast cancer in a
      developing country.
AB  - Scarce radiation resources and an often poor, rural population make single
      fraction, definitive intra-operative radiation (IORT) ideal for developing
      countries. From 2002 to 2005 IORT in breast conservation was administered
      utilizing existing infrastructure in an extremely resource-restricted
      environment. After tumor excision an applicator was introduced into the tumor
      bed. An existing Ir (192) after loader delivered a single fraction (21 Gy). Of
      thirty nine patients treated with 84 months follow-up, one patient suffered
      local, four regional and three systemic relapse. One patient died of disease, 2
      of unrelated causes for a local control rate of 95% and a disease-specific
      survival of 95%. Cosmetic outcome was perceived excellent. IORT using existing
      after loaders and a low cost applicator greatly reduced health care resources.
      This extends breast conservation to indigent patients who cannot adhere to
      lengthy EBRT protocols.

PMID- 22374251
TI  - Near-field quantification of complement receptor 1 (CR1/CD35) protein clustering
      in human erythrocytes.
AB  - We investigate the distribution of the membrane protein complement receptor 1
      (CR1/CD35) in human erythrocyte membrane ghosts using scanning near-field optical
      microscopy. Recent studies have demonstrated that levels of Abeta peptide,
      associated with Alzheimers disease (AD) and present in brain and peripheral
      blood, vary significantly when bound by complement C3b-dependent adherence to
      CR1. It is unknown why patients with AD have a markedly impaired ability to bind
      Abeta to CR1 via this mechanism, but one possibility is a defect in the
      localization and/or conformation of CR1 in the membrane. Scanning near-field
      optical microscopy does not require the harsh preparation of electron microscopy
      techniques and may therefore be better suited for measuring membrane protein
      distributions. The clustering phenomenon of CR1 identified in electron microscopy
      studies is confirmed and quantified. The standard deviation of the inter-cluster
      spacing of CR1 is constant (79 +/- 9 nm) across erythrocytes with between 61 and
      124 clusters per membrane ghost.

PMID- 22374252
TI  - Blue rubber bleb nevus: an uncommon cause of intestinal intussusception.
AB  - The blue rubber bleb nevus syndrome or Bean syndrome is a rare disorder
      characterized by cutaneous and gastrointestinal vascular malformations. A 5-year
      old girl with Bean syndrome hospitalized in a pediatric unit came under our
      observation with abdominal pain and vomiting. An X-ray of the abdomen showed an
      intestinal occlusion and an ultrasonography showed a suspected intestinal
      invagination. She underwent emergency laparoscopic surgery using three trocars.
      Laparoscopy revealed a huge ascitis and multiple vascular lesions located on the
      loops and on the parietal peritoneum, and we identified also an ileo-ileal
      invagination. We performed a laparoscopic disinvagination that showed one huge
      vascular lesion producing the invagination and causing a stenosis of intestinal
      lumen. We performed an intestinal resection after exteriorizing the loops through
      the umbilicus as well as a termino-terminal ileal anastomosis. CONCLUSIONS: Our
      case shows that an intestinal invagination due to Bean syndrome is extremely rare
      in pediatric patients but possible. In the emergency, laparoscopy seems to be a
      safe and effective procedure to confirm the diagnosis and to perform the
      disinvagination mini-invasivally. In addition, laparoscopy permits to have a
      clear picture of other intra-abdominal lesions linked to Bean syndrome.

PMID- 22374253
TI  - Interactions between dopamine transporter and cannabinoid receptor ligands in
      rhesus monkeys.
AB  - RATIONALE: Delta(9)-tetrahydrocannabinol (Delta(9)-THC) modifies dopamine efflux.
      However, the extent to which cannabinoid and dopamine drugs modify each other's
      behavioral effects has not been fully established. OBJECTIVES: This study
      examined dopamine releasers and/or transport inhibitors alone and in combination
      with cannabinoids in two drug discrimination assays. METHODS: Experimentally and
      pharmacologically experienced rhesus monkeys (n = 5) discriminated Delta(9)-THC
      (0.1 mg/kg i.v.) from vehicle while responding under a fixed ratio 5 schedule of
      stimulus-shock termination. A separate group (n = 6) of monkeys responded under
      the same schedule, received daily Delta(9)-THC (1 mg/kg/12 h s.c.), and
      discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.), i.e.,
      cannabinoid withdrawal, from vehicle. A sign of withdrawal sign (head shaking)
      was examined in monkeys receiving Delta(9)-THC daily. RESULTS: Rimonabant
      antagonized the Delta(9)-THC discriminative stimulus and a dose of Delta(9)-THC
      greater than the daily treatment attenuated the rimonabant discriminative
      stimulus. In monkeys discriminating Delta(9)-THC, the dopamine transporter
      ligands cocaine, amphetamine, bupropion, RTI 113, and RTI 177 produced a maximum
      of 2% responding on the drug lever and blocked the discriminative stimulus
      effects of Delta(9)-THC. In Delta(9)-THC treated monkeys discriminating
      rimonabant, the dopamine transporter ligands partially substituted for and
      increased the potency of rimonabant to produce discriminative stimulus effects.
      The dopamine antagonist haloperidol enhanced the Delta(9)-THC discriminative
      stimulus without significantly modifying the rimonabant discriminative stimulus.
      Imipramine and desipramine, which have low affinity for dopamine transporters,
      were less effective in modifying either the Delta(9)-THC or rimonabant
      discriminations. The dopamine transporter ligands and haloperidol attenuated head
      shaking, whereas imipramine and desipramine did not. CONCLUSIONS: Dopamine
      release and/or inhibition of dopamine transport blocks detection of Delta(9)-THC
      and is potentially the mechanism by which some therapeutics (e.g., bupropion)
      reduce the subjective effects of marijuana and enhance the subjective effects of
      marijuana withdrawal.

PMID- 22374254
TI  - Neuropsychological effects associated with recreational cocaine use.
AB  - RATIONALE: Recent evidence suggests that recreational cocaine use is on the
      increase, with the UK reporting one of the highest levels of use in the EU
      (EMCDDA 2010). Nevertheless, very few studies have addressed the
      neuropsychological effects associated with non-dependent recreational cocaine
      use. OBJECTIVES: The current study aimed to assess whether recreational cocaine
      users show neuropsychological deficits on a battery of tests, previously shown to
      be sensitive to cocaine-dependent and psychosis-prone individuals. Schizotypal
      traits were also measured. METHODS: Recreational cocaine users (n = 17) were
      compared with controls (n = 24) on drug use patterns, the General Health
      Questionnaire, the Brief Schizotypal Personality Questionnaire (SPQ-B) and four
      neuropsychological tasks: spatial working memory, intra/extra-dimensional set
      shifting, the Stocking of Cambridge and the rapid visual processing. RESULTS:
      Relative to controls, recreational cocaine users produced significantly more
      errors on the intra/extra-dimensional set shift task and completed fewer stages,
      made significantly more six box stage errors on the spatial working memory task,
      and made significantly more errors and fewer hits, with overall poorer detection
      rates on the rapid visual processing task. Recreational cocaine users reported
      significantly higher scores on the cognitive perceptual and disorganised thinking
      SPQ-B subscales and total SPQ-B scores compared to controls. CONCLUSIONS:
      Recreational cocaine users displayed impairments on tasks tapping sustained
      attention, attentional shifting and spatial memory and reported higher
      schizotypal trait expression. These findings are consistent with the emerging
      literature suggesting subtle cognitive deficits, putatively reflecting underlying
      dopaminergic dysfunction, in non-dependent, recreational cocaine users.

PMID- 22374255
TI  - Reversal of cocaine withdrawal-induced anxiety by ondansetron, buspirone and
      propranolol.
AB  - Cocaine is used worldwide and considered a public health problem. Relapse from
      addiction is one of the difficulties faced by cocaine users, and in most cases
      according to the period of abstinence, users may present symptoms such as anxiety
      or depression. To evaluate the anxiety-like behavior induced by different
      periods, rats were treated for 7 days with cocaine 20 mg/kg, i.p., and 24 h, 7
      and 21 days after drug withdrawal were submitted to the elevated plus maze (EPM)
      and the open field (OF) tests. In different protocol, propranolol (10 mg/kg,
      i.p.), ondansetron (4 mg/kg, i.p.) and buspirone (5 mg/kg, i.p.) were
      administered once after 24 h and 7 days of abstinence from cocaine to evaluate
      possible reversal or attenuation of the symptoms caused by cocaine withdrawal.
      EPM results showed a reduction in all parameters after 24 h and 7 days of the
      last exposure to cocaine, indicating anxiety-like behavior. In the OF test, 24 h
      and 7 days of abstinence showed increased locomotor activity, while in the
      withdrawal 21 days the animals not alter the locomotor activity. The
      administration of propranolol, ondansetron or buspirone after a 24 h abstinence
      period reduced the animals anxiety in the EPM, and in the OF all drugs were able
      to reduce locomotor activity. After abstinence 7 d, the drugs reduced locomotor
      activity in the OF, in the EMP propranolol and ondansetron reversed the
      anxiogenic effect induced by cocaine. These results suggest that the treatment of
      anxyogenic effects of abstinence from cocaine is dependent on the period of the
      withdrawal.

PMID- 22374256
TI  - The actions of mdivi-1, an inhibitor of mitochondrial fission, on rapidly
      activating delayed-rectifier K+ current and membrane potential in HL-1 murine
      atrial cardiomyocytes.
AB  - Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated
      mitochondrial fission. However, the mechanisms through which this compound
      interacts directly with ion currents in heart cells remain unknown. In this
      study, its effects on ion currents and membrane potential in murine HL-1
      cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi
      1 decreased the amplitude of tail current (I(tail)) for the rapidly activating
      delayed-rectifier K+ current (I(Kr)) in a concentration-dependent manner with an
      IC50 value at 11.6 MUM, a value that resembles the inhibition requirement for
      mitochondrial division. It shifted the activation curve of I(tail) to depolarized
      voltages with no change in the gating charge. However, mdivi-1 did not alter the
      rate of recovery from current inactivation. In cell-attached configuration, mdivi
      1 inside the pipette suppressed the activity of acetylcholine-activated K+
      channels without modifying the single-channel conductance. Mdivi-1 (30 MUM)
      slightly depressed the peak amplitude of Na+ current with no change in the
      overall current-voltage relationship. Under current-clamp recordings, addition of
      mdivi-1 resulted in prolongation for the duration of action potentials (APs) and
      to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary
      GH3 cells, mdivi-1 was effective in directly suppressing the amplitude of ether-a
      go-go-related gene-mediated K+ current. Therefore, the lengthening of AP duration
      and increased firing of APs caused by mdivi-1 can be primarily explained by its
      inhibition of these K+ channels enriched in heart cells. The observed effects of
      mdivi-1 on ion currents were direct and not associated with its inhibition of
      mitochondrial division.

PMID- 22374257
TI  - Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment
      of neutrophils in abdominal sepsis.
AB  - We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive
      mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated
      with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP).
      Lung levels of myeloperoxidase (MPO) and histological tissue damage were
      determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in
      neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1
      expression and F-actin formation were also determined in isolated neutrophils up
      to 3h after stimulation with CXCL2. Labeled and activated neutrophils co
      incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively
      transferred to CLP mice. Y-27632 reduced the CLP-induced pulmonary injury and MPO
      activity as well as Mac-1 on neutrophils. Neutrophil F-actin formation peaked at
      6h and returned to baseline levels 24h after CLP induction. Rho-kinase inhibition
      decreased CLP-provoked F-actin formation in neutrophils. CXCL2 rapidly increased
      Mac-1 expression and F-actin formation in neutrophils. Co-incubation with Y-27632
      abolished CXCL2-induced Mac-1 up-regulation and formation of F-actin in
      neutrophils. Notably, co-incubation with cytochalasin B inhibited formation of F
      actin but did not reduce Mac-1 expression on activated neutrophils. Adoptive
      transfer experiments revealed that co-incubation of neutrophils with the anti-Mac
      1 antibody or cytochalasin B significantly decreased pulmonary accumulation of
      neutrophils in septic mice. Our data show that targeting Rho-kinase effectively
      reduces neutrophil recruitment and tissue damage in abdominal sepsis. Moreover,
      these findings demonstrate that Rho-kinase-dependent neutrophil accumulation in
      septic lung injury is regulated by both adhesive and mechanical mechanisms.

PMID- 22374258
TI  - Inhibitory effects of magnolol on voltage-gated Na+ and K+ channels of NG108-15
      cells.
AB  - Magnolol, a polyphenolic compound isolated from Houpu, a Chinese herb from the
      bark of Magnolia officinalis, has been reported to have in vitro and in vivo
      neuroprotective effects. In spite of these reported beneficial effects, studies
      on the direct impact of magnolol on neuronal ion channels have been scarce.
      Whether magnolol affects voltage-gated Na(+) channels (VGSC) and voltage-gated
      K(+) (Kv) channels is unknown. Using the whole-cell voltage-clamp method, we
      studied the effects of magnolol on voltage-gated ion channels in neuronal NG108
      15 cells. Magnolol inhibited VGSC channels with mild state-dependence (IC(50) of
      15 and 30 MUM, at holding potentials of -70 and -100 mV, respectively). No
      frequency-dependence was observed in magnolol block. Magnolol caused a left-shift
      of 18 mV in the steady-state inactivation curve but did not affect the voltage
      dependence of activation. Magnolol inhibited Kv channels with an IC(50) of 21
      MUM, and it caused a 20-mV left-shift in the steady-state inactivation curve
      without affecting the voltage-dependence of activation. In conclusion, magnolol
      is an inhibitor of both VGSC and Kv channels and these inhibitory effects may in
      part contribute to some of the reported neuroprotective effects of magnolol.

PMID- 22374259
TI  - 5-HT 2A receptor activation of the external urethral sphincter and 5-HT 2C
      receptor inhibition of micturition: a study based on pharmacokinetics in the
      anaesthetized female rat.
AB  - Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role
      in the regulation of micturition. Bolus doses of 5-HT(2A/2C) receptor agonists
      have been shown to activate the external urethral sphincter (EUS) and to inhibit
      micturition. This study was designed to determine the contribution of these two 5
      HT receptor subtypes to activation of the EUS and inhibition of micturition
      utilising pharmacokinetic knowledge to better control drug exposure. Recordings
      of urethral and bladder pressure, EUS-Electromyogram (EMG), the micturition
      reflex induced by bladder filling, blood pressure and heart rate were made in
      anaesthetized female rats. The effects of intravenous (i.v.) infusions of the 5
      HT(2) receptor agonist (2S)-1-(6-chloro-5-fluoroindol-1-yl)propan-2-amine
      fumarate (Ro 60-0175) in the absence or presence of the selective 5-HT(2C)
      receptor antagonist 6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]
      2,3-dihydroindole-1-carboxamide dihydrochloride (SB 242084) or 5-HT(2A) receptor
      antagonist (R)-(2,3-dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4
      yl]methanol (MDL-100,907) were studied on these variables. Continuous infusion of
      increasing concentrations of Ro 60-0175 only evoked EUS-EMG activity at the
      highest concentration, which was blocked by co-infusion of MDL-100,907 but not SB
      242084. Urethral pressure was unaffected by any drug infusion. Ro 60-0175 at the
      lowest concentration inhibited the micturition reflex but as the concentration
      increased this was reversed to facilitation. SB 242084 blocked the inhibition
      while MDL-100,907 blocked the excitation. Activation of 5-HT(2A) not 5-HT(2C)
      receptors evoked EUS-EMG activity. In conclusion, 5-HT(2A) receptor activation
      facilitated the micturition reflex and evoked EUS-EMG while 5-HT(2C) receptor
      activation only inhibited the micturition reflex.

PMID- 22374260
TI  - Cannabinoid agonist WIN 55,212-2 prevents the development of paclitaxel-induced
      peripheral neuropathy in rats. Possible involvement of spinal glial cells.
AB  - Spinal glial activation contributes to the development and maintenance of chronic
      pain states, including neuropathic pain of diverse etiologies. Cannabinoid
      compounds have shown antinociceptive properties in a variety of neuropathic pain
      models and are emerging as a promising class of drugs to treat neuropathic pain.
      Thus, the effects of repeated treatment with WIN 55,212-2, a synthetic
      cannabinoid agonist, were examined throughout the development of paclitaxel
      induced peripheral neuropathy. Painful neuropathy was induced in male Wistar rats
      by intraperitoneal (i.p.) administration of paclitaxel (1mg/kg) on four alternate
      days. Paclitaxel-treated animals received WIN 55,212-2 (1mg/kg, i.p.) or
      minocycline (15 mg/kg, i.p.), a microglial inhibitor, daily for 14 days,
      simultaneous with the antineoplastic. The development of hypersensitive behaviors
      was assessed on days 1, 7, 14, 21 and 28 following the initial administration of
      drugs. Both the activation of glial cells (microglia and astrocytes) at day 29
      and the time course of proinflammatory cytokine release within the spinal cord
      were also determined. Similar to minocycline, repeated administration of WIN
      55,212-2 prevented the development of thermal hyperalgesia and mechanical
      allodynia in paclitaxel-treated rats. WIN 55,212-2 treatment also prevented
      spinal microglial and astrocytic activation evoked by paclitaxel at day 29 and
      attenuated the early production of spinal proinflammatory cytokines (interleukin
      (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha). Our results confirm
      changes in the reactivity of glial cells during the development of peripheral
      neuropathy induced by paclitaxel and support a preventive effect of WIN 55,212-2,
      probably via glial cells reactivity inactivation, on the development of this
      neuropathy.

PMID- 22374261
TI  - Platelets regulate P-selectin expression and leukocyte rolling in inflamed
      venules of the pancreas.
AB  - Recent data suggest that platelets regulate inflammatory changes and tissue
      damage in acute pancreatitis although the role of platelets in leukocyte
      endothelium interactions in the pancreatic microcirculation is not known. The aim
      of this study was to define the impact of platelets on leukocyte rolling and
      adhesion in acute pancreatitis. Acute pancreatitis was induced in C57BL/6 mice by
      caerulein challenge. Mice were treated with an anti-GP1balpha (CD42b) antibody,
      which depletes platelets, or a control antibody before caerulein. Leukocyte
      rolling and adhesion were determined by the use of intravital fluorescence
      microscopy 18 h after the last dose of caerulein. In separate experiments,
      leukocyte-endothelium interactions were determined before and after
      administration of an anti-P-selectin, anti-PSGL-1 and a control antibody in mice
      with caerulein pancreatitis. Circulating platelet-neutrophil aggregates and
      pancreatic P-selectin mRNA were quantified 1 and 6h respectively after caerulein
      challenge. Caerulein administration increased leukocyte and platelet interactions
      in the pancreatic microvasculature, increased tissue damage and expression of P
      selectin mRNA in the pancreas as well as platelet-neutrophil complexes in the
      circulation. Notably, platelet depletion markedly reduced caerulein-provoked
      leukocyte rolling and adhesion in postcapillary venules. Interestingly, depletion
      of platelets significantly decreased caerulein-induced gene expression of P
      selectin in the pancreas. Moreover, immunoneutralization of P-selectin and PSGL-1
      abolished leukocyte rolling in the pancreatic venules triggered by caerulein. Our
      novel findings demonstrate that platelets regulate leukocyte rolling in acute
      pancreatitis via induction of P-selectin, which was critical in supporting
      leukocyte rolling in inflamed venules of the pancreas.

PMID- 22374262
TI  - The role of mu opioid receptors in psychomotor stimulation and conditioned place
      preference induced by morphine-6-glucuronide.
AB  - Previous studies have shown that morphine-6-glucuronide (M6G), a metabolite of
      morphine, induces reward and psychomotor stimulation but the role of the mu
      opioid receptor in these actions of the drug is not fully characterized. Thus,
      using mice lacking exon-2 of the mu opioid receptor and their wild-type
      littermates/controls, we determined the role of this receptor in psychomotor
      stimulation, sensitization, and conditioned place preference (CPP) induced by
      M6G. For comparison, we also assessed the role of the mu opioid receptor in the
      rewarding action of morphine. For the measurement of locomotor activity and
      sensitization, mice were habituated to motor activity chambers for 1h, then
      injected with M6G (10mg/kg) and locomotor activity was recorded for an additional
      1h. The same treatment was given for five days and mice were tested for
      sensitization a week later. For the CPP experiments, mice were tested for
      baseline place preference on day 1, then received single or repeated alternate
      day saline/drug or drug/saline conditioning and tested for CPP the following day.
      Mice were also tested for CPP under a drugged state. M6G induced psychomotor
      stimulation, a response that was enhanced upon repeated administration of the
      drug, showing that locomotor sensitization developed to the motor stimulatory
      action of M6G. However, M6G induced a weaker CPP response compared to morphine.
      None of these actions of M6G was detected in mice lacking the mu opioid receptor.
      Together, the current results suggest that M6G induces psychomotor stimulation
      and a weaker rewarding action via the mu opioid receptor.

PMID- 22374264
TI  - Donor disease transmission:  minimizing the risks and maximizing the benefits.

PMID- 22374263
TI  - Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD)
      MRI.
AB  - Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR)
      imaging of skeletal muscle mainly depends on changes of oxygen saturation in the
      microcirculation. In recent years, an increasing number of studies have evaluated
      the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases,
      such as peripheral arterial occlusive disease, diabetes mellitus, and chronic
      compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e.,
      high spatial resolution, no exposure to ionizing radiation, with functional
      information of local microvascular perfusion. Due to intrinsic contrast provoked
      via changes in hemoglobin oxygen saturation, it is a safe and easy applicable
      procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of
      skeletal muscle is a potential new diagnostic tool in the clinical evaluation of
      vascular, inflammatory, and muscular pathologies. Our review focuses on the
      current evidence concerning the use of BOLD MR imaging of skeletal muscle under
      pathological conditions and highlights ways for future clinical and scientific
      applications.

PMID- 22374265
TI  - Infections and organ transplantation: new challenges for prevention and treatment
      -a colloquium.

PMID- 22374266
TI  - Adolescent daughters' romantic competence: the role of divorce, quality of
      parenting, and maternal romantic history.
AB  - This study examined the links between parental divorce, quality of maternal
      parenting, spousal relationships and middle adolescent romantic competence in 80
      mother-adolescent daughter pairs (40 divorced). Mothers were asked to describe
      their attitudes and behaviors with regard to their daughters' romantic behavior.
      In addition, mothers were interviewed about their own romantic experiences when
      they were at the age of their daughters. Adolescent girls (mean age = 16.98
      years; range 16-18) were administered a comprehensive interview about romantic
      competence. Findings indicated that adolescent girls from divorced families
      showed lower levels of romantic competence, which were expressed in their
      behavior, attitudes toward relationships and skill in handling those
      relationships. Divorce was found to have had an adverse effect on girls' romantic
      competence, whereas continued adaptive parenting and spousal relationships
      alleviated the effect of divorce. Mothers' coherent representation of their own
      adolescent romantic experiences also alleviated the effect of divorce on
      daughters' romantic behavior. Results show the important role of family
      relationships in fostering romantic competence among adolescent girls.

PMID- 22374267
TI  - Looking back to look forward: from paper to practice.

PMID- 22374268
TI  - Empowering nutrition gatekeepers: policy with a small "p".

PMID- 22374269
TI  - Putting MyPlate to work for nutrition educators.

PMID- 22374270
TI  - Return to sport following hip injury.
AB  - Returning to both recreational and competitive sport requires the patient
      demonstrate the ability to perform their activity without pain, without
      compensation and without apprehension. The primary focus of this article will be
      to provide progressive weight bearing phased treatment solutions and both
      objective and empirical return to play testing suggestions. In addition to
      satisfactorily completing the test battery with maximum effort, the patient must
      demonstrate the ability to meet the demands for competing within their respective
      sport specific environment. Returning to competition will most likely include
      early phase movement screening and clinical clearance followed by late phase
      athletic and field testing. Hip structure will and must influence training
      program design. It is therefore important to recognize that indications for
      return to play must not focus on a single rehabilitation or exercise variable,
      but rather a combination of clinical, functional and sport specific demands.

PMID- 22374271
TI  - Colorless green ideas (can) prime furiously.
AB  - That similar words can prime one another is not news. However, this phenomenon
      can be exploited to make inferences about the organization of conceptual
      representations. What types of similarity matter? Although there is evidence that
      similarity of function, shape, and even manner of manipulation is reflected in
      semantic memory, evidence for organization on the basis of color similarity is
      sparse. This lack of evidence is surprising: Intuition suggests that color is a
      prominent feature of many object concepts. The research reported here clarifies
      this puzzle and illustrates the dynamic nature of conceptual representations. Our
      research demonstrates color-based priming (e.g., "emerald" primes "cucumber") in
      participants who completed a Stroop color-naming task before a priming task.
      Notably, the size of the Stroop effect predicted the size of the priming effect.
      When the order of tasks was reversed, priming effects were eliminated. By
      demonstrating that both extrinsic and intrinsic factors can influence conceptual
      activation, our findings have implications for theories of semantic memory.

PMID- 22374272
TI  - 3d-Metal derivatives of the [Cu(I)(SO3)4]7- ion: structure and magnetism.
AB  - The Cu(SO(3))(4)(7-) anion, which consists of a tetrahedrally coordinated Cu(I)
      centre coordinated to four sulfur atoms, is able to act as a multidentate ligand
      in discrete and infinite supramolecular species. The slow oxidation of an aqueous
      solution of Na(7)Cu(SO(3))(4) yields a mixed oxidation state, 2D network of
      composition Na(5){[Cu(II)(H(2)O)][Cu(I)(SO(3))(4)]}.6H(2)O. The addition of
      Cu(II) and 2,2'-bipyridine to an aqueous Na(7)Cu(SO(3))(4) solution leads to the
      formation of a pentanuclear complex of composition
      {[Cu(II)(H(2)O)(bipy)](4)[Cu(I)(SO(3))(4)]}(+); a combination of hydrogen bonding
      and pi-pi stacking interactions leads to the generation of infinite parallel
      channels that are occupied by disordered nitrate anions and water molecules. A
      pair of Cu(SO(3))(4)(7-) anions each act as a tridentate ligand towards a single
      Mn(II) centre when Mn(II) ions are combined with an excess of Cu(SO(3))(4)(7-).
      An anionic pentanuclear complex of composition
      {[Cu(I)(SO(3))(4)](2)[Fe(III)(H(2)O)](3)(O)} is formed when Fe(II) is added to a
      Cu(+)/SO(3)(2-) solution. Hydrated ferrous [Fe(H(2)O)(6)(2+)] and sodium ions act
      as counterions for the complexes and are responsible for the formation of an
      extensive hydrogen bond network within the crystal. Magnetic susceptibility
      studies over the temperature range 2-300 K show that weak ferromagnetic coupling
      occurs within the Cu(II) containing chains of
      Na(5){[Cu(II)(H(2)O)][Cu(I)(SO(3))(4)]}.6H(2)O, while zero coupling exists in the
      pentanuclear cluster {[Cu(II)(H(2)O)(bipy)](4)[Cu(I)(SO(3))(4)]}(NO(3)).H(2)O.
      Weak Mn(II)-O-S-O-Mn(II) antiferromagnetic coupling occurs in
      Na(H(2)O)(6){[Cu(I)(SO(3))(4)][Mn(II)(H(2)O)(2)](3)}, the latter formed when Mn
      was in excess during synthesis. The compound,
      Na(3)(H(2)O)(6)[Fe(II)(H(2)O)(6)](2){[Cu(I)(SO(3))(4)](2)[Fe(III)(H(2)O)](3)(O)}.
      (2)O, contained trace magnetic impurities that affected the expected magnetic
      behaviour.

PMID- 22374273
TI  - Ultrasound imaging of the anal sphincter complex: a review.
AB  - Endoanal ultrasound is now regarded as the gold standard for evaluating anal
      sphincter pathology in the investigation of anal incontinence. The advent of
      three-dimensional ultrasound has further improved our understanding of the two
      dimensional technique. Endoanal ultrasound requires specialised equipment and its
      relative invasiveness has prompted clinicians to explore alternative imaging
      techniques. Transvaginal and transperineal ultrasound have been recently
      evaluated as alternative imaging modalities. However, the need for technique
      standardisation, validation and reporting is of paramount importance. We
      conducted a MEDLINE search (1950 to February 2010) and critically reviewed
      studies using the three imaging techniques in evaluating anal sphincter
      integrity.

PMID- 22374274
TI  - Recommendations for the use of PET and PET-CT for radiotherapy planning in
      research projects.
AB  - With the increasing use of positron emission tomography (PET) for disease
      staging, follow-up and therapy monitoring in a number of oncological indications
      there is growing interest in the use of PET and PET-CT for radiation treatment
      planning. In order to create a strong clinical evidence base for this, it is
      important to ensure that research data are clinically relevant and of a high
      quality. Therefore the National Cancer Research Institute PET Research Network
      make these recommendations to assist investigators in the development of
      radiotherapy clinical trials involving the use of PET and PET-CT. These
      recommendations provide an overview of the current literature in this rapidly
      evolving field, including standards for PET in clinical trials, disease staging,
      volume delineation, intensity modulated radiotherapy and PET-augmented planning
      techniques, and are targeted at a general audience. We conclude with specific
      recommendations for the use of PET in radiotherapy planning in research projects.

PMID- 22374275
TI  - Onyx 18 embolisation of dural arteriovenous fistula via arterial and venous
      pathways: preliminary experience and evaluation of the short-term outcomes.
AB  - OBJECTIVE: This paper mainly focuses on our preliminary experience and short-term
      outcome evaluation of embolisation of non-cavernous dural arteriovenous fistulas
      (ncsDAVFs) and cavernous sinus dural arteriovenous fistulas (csDAVFs) using Onyx
      18 (ev3, Plymouth, MN), and in combination with coils, via arterial and venous
      approaches, respectively. METHODS: Between August 2008 and March 2010, 21 DAVFs
      (11 ncsDAVFs and 10 csDAVFs; age range: 28-68 years; 12 females and 9 males) were
      undertaken. Borden classification showed Type III in 1 and Type II in 10
      ncsDAVFs, and Type II in 4 and Type I in 6 csDAVFs. Onyx 18 was used in 11
      ncsDAVFs (10 via single feeder and 1 via 2 feeders). Onyx 18 or in combination
      with coils was used in 10 csDAVFs (9 via the inferior petrosal sinus and 1 via
      the superior ophthalmic vein). RESULTS: Total occlusion in immediate angiography
      was achieved in 18 cases (85.7%; 10 ncsDAVFs and 8 csDAVFs), and near-total
      occlusion in 1 ncsDAVF and 2 csDAVFs. Onyx 18 was migrated into normal
      vasculature in two ncsDAVFs without any sequelae. One csDAVF had VI cranial nerve
      palsy post-operatively, which completely recovered 2 weeks post-embolisation.
      Follow-up angiography at 3-12 months showed complete occlusion in 20 cases
      (95.2%; 10 ncsDAVFs and 10 csDAVFs). One ncsDAVF (4.8%) recurred after 3 months
      and was successfully re-embolised. CONCLUSION: Preliminary results achieved after
      embolising 11 ncsDAVFs and 10 csDAVFs using Onyx 18 and in combination with coils
      via arterial and venous pathways, respectively, appeared to be safe, feasible and
      effective, as 95.2% of cases were totally occluded without any clinical sequelae.

PMID- 22374276
TI  - Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with
      pathological examination.
AB  - OBJECTIVE: To investigate the correlation between enhancement patterns of
      intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and
      pathological findings. METHODS: The CEUS enhancement patterns of 40
      pathologically proven ICC lesions were retrospectively analysed. Pathologically,
      the degree of tumour cell and fibrosis distribution in the lesion was semi
      quantitatively evaluated. RESULTS: 4 enhancement patterns were observed in the
      arterial phase for 32 mass-forming ICCs: peripheral rim-like hyperenhancement
      (n=19); heterogeneous hyperenhancement (n=6); homogeneous hyperenhancement (n=3);
      and heterogeneous hypo-enhancement (n=4). Among the four enhancement patterns,
      the differences in tumour cell distribution were statistically significant
      (p<0.05). The hyperenhancing area on CEUS corresponded to more tumour cells for
      mass-forming ICCs. Heterogeneous hyperenhancement (n=2) and heterogeneous hypo
      enhancement (n=2) were observed in the arterial phase for four periductal
      infiltrating ICCs. In this subtype, fibrosis was more commonly found in the
      lesions. Heterogeneous hyperenhancement (n=1) and homogeneous hyperenhancement
      (n=3) were observed in the arterial phase for four intraductal growing ICCs. This
      subtype tended to have abundant tumour cells. CONCLUSION: The CEUS findings of
      ICC relate to the degree of carcinoma cell proliferation at pathological
      examination. Hyperenhancing areas in the tumour always indicated increased
      density of cancer cells.

PMID- 22374277
TI  - Effect of CT fluoroscopy-guided transpulmonary radiofrequency ablation of liver
      tumours on the lung.
AB  - OBJECTIVE: We retrospectively evaluated the effect of transpulmonary
      radiofrequency ablation (RFA) of liver tumours on the lung. METHODS: 16 patients
      (10 males and 6 females; mean age, 65.2 years) with 16 liver tumours (mean
      diameter 1.5 cm) underwent transpulmonary RFA under CT fluoroscopic guidance. The
      tumours were either hepatocellular carcinoma (n=14) or liver metastasis (n=12).
      All 16 liver tumours were undetectable with ultrasonography. The pulmonary
      function values at 3 months after transpulmonary RFA were compared with baseline
      (i.e. values before RFA). RESULTS: In 8 of 16 sessions, minor pulmonary
      complications occurred, including small pneumothorax (n=8) and small pleural
      effusion (n=1). In two sessions, major pulmonary complications occurred,
      including pneumothorax requiring a chest tube (n=2). These chest tubes were
      removed at 4 and 6 days, and these patients were discharged 7 and 10 days after
      RFA, respectively, without any sequelae. The pulmonary function values we
      evaluated were forced expiratory volume in 1 s (FEV1.0) and vital capacity (VC).
      The mean values of FEV1.0 before and 3 months after RFA were 2.55 l and 2.59 l,
      respectively; the mean values of VC before and 3 months after RFA were 3.20 l and
      3.27 l, respectively. These pulmonary values did not show any significant
      worsening (p=0.393 and 0.255 for FEV1.0 and VC, respectively). CONCLUSION: There
      was no significant lung injury causing a fatal or intractable complication after
      transpulmonary RFA of liver tumours.

PMID- 22374278
TI  - Carcinoma of unknown primary: key radiological issues from the recent National
      Institute for Health and Clinical Excellence guidelines.
AB  - Carcinoma of unknown primary origin (CUP) accounts for 3-5% of cancer cases and
      is the fourth most common cause of cancer death in the UK. CUP management is
      challenging, partly owing to the heterogeneity of the condition and its
      presentation, but also owing to the lack of dedicated clinical services for these
      patients. The recent National Institute for Health and Clinical Excellence (NICE)
      guidelines on metastatic malignancy of unknown primary origin were developed to
      improve the co-ordination of diagnostic and clinical services at hospitals
      treating cancer patients in England and Wales, in particular by the setting up of
      CUP teams to manage these patients. Radiologists have a vital role in the
      diagnosis of these patients and should work closely with the CUP team to
      streamline the diagnostic pathway. This article summarises areas of the NICE
      guidelines relevant to radiology and discusses the radiological management of
      patients with CUP, including initial investigation, the importance of biopsy, the
      management of specific presentations, special investigations and organisational
      issues.

PMID- 22374279
TI  - Strict X-ray beam collimation for facial bones examination can increase lens
      exposure.
AB  - OBJECTIVES: It is well accepted that collimation is a cost-effective dose
      reducing tool for X-ray examinations. This phantom-based study investigated the
      impact of X-ray beam collimation on radiation dose to the lenses of the eyes and
      thyroid along with the effect on image quality in facial bone radiography.
      METHODS: A three-view series (occipitomental, occipitomental 30 and lateral) was
      investigated, and radiation doses to the lenses and thyroid were measured using
      an Unfors dosemeter. Images were assessed by six experienced observers using a
      visual grading analysis and a total of 5400 observations were made. RESULTS:
      Strict collimation significantly (p<0.0001) reduced the radiation dose to the
      lenses of the eyes and thyroid when using a fixed projection-specific exposure.
      With a variable exposure technique (fixed exit dose, to simulate the behaviour of
      an automatic exposure control), while strict collimation was again shown to
      reduce thyroid dose, higher lens doses were demonstrated when compared with
      larger fields of exposure. Image quality was found to significantly improve using
      strict collimation, with observer preference being demonstrated using visual
      grading characteristic curves. CONCLUSION: The complexities of optimising
      radiographic techniques have been shown and the data presented emphasise the
      importance of examining dose-reducing strategies in a comprehensive way.

PMID- 22374280
TI  - Review of the principal extra spinal pathologies causing sciatica and new MRI
      approaches.
AB  - In this paper we illustrate the principal extraspinal pathologies causing
      sciatica and new approaches for the study of structures such as the lumbosacral
      plexus (LSP). Visualisation of the LSP in its entirety is difficult with
      conventional two-dimensional MRI sequences owing to its oblique orientation. In
      our institution, we have found that the utilisation of three-dimensional short
      tau inversion-recovery sampling perfection with application-optimised contrasts
      using different flip angle evolutions sequence is helpful, allowing multiplanar
      and maximum intensity projection reconstructions in the coronal oblique plane and
      curvilinear reformats through the plexus. Diffusion tensor imaging enables the
      observation of microstructural changes and can be useful in surgical planning.
      The normal anatomy of the LSP, its different extraspinal pathologies and
      differential diagnoses are thoroughly presented.

PMID- 22374281
TI  - Sparseness of the trabecular pattern on dental radiographs: visual assessment
      compared with semi-automated measurements.
AB  - OBJECTIVE: In diagnostic imaging; human perception is the most prominent, yet
      least studied, source of error. A better understanding of image perception will
      help to improve diagnostic performance. This study focuses on the perception of
      coarseness of trabecular patterns on dental radiographs. Comparison of human
      vision with machine vision should yield knowledge on human perception. METHOD: In
      a study on identifying osteoporotic patients, dental radiographs were made from
      505 post-menopausal women aged 45-70 years. Intra-oral radiographs of the lower
      and upper jaws were made. Five observers graded the trabecular pattern as dense,
      sparse or mixed. The five gradings were combined into a single averaged observer
      score per jaw. The radiographs were scanned and a region of interest (ROI) was
      indicated on each. The ROIs were processed with image analysis software measuring
      25 image features. Pearson correlation and multiple linear regression were used
      to compare the averaged observer score with the image features. RESULTS: 14 image
      features correlated significantly with the observer judgement for both jaws. The
      strongest correlation was found for the average grey value in the ROI. Other
      features, describing that osteoporotic patients have fewer but bigger marrow
      spaces than controls, correlated less with the sparseness of the trabecular
      pattern than a rather crude measure for structure such as the average grey value.
      CONCLUSION: Human perception of the sparseness of trabecular patterns is based
      more on average grey values of the ROI than on geometric details within the ROI.

PMID- 22374282
TI  - Percutaneous ultrasound-guided thermal ablation for intrahepatic
      cholangiocarcinoma.
AB  - OBJECTIVE: The objective of this study was to evaluate the treatment efficacy and
      overall survival (OS) of percutaneous ultrasound-guided thermal ablation by means
      of microwave ablation or radiofrequency ablation for intrahepatic
      cholangiocarcinoma (ICC). METHODS: 18 patients with 25 ICC nodules underwent
      ultrasound-guided thermal ablation with curative intention. 8 patients were
      primary cases and 10 were recurrent cases after curative resection. The local
      treatment response, complications and survivals were analysed. RESULTS: Complete
      ablation was achieved in 23 (92.0%, 23/25) nodules (diameter, 0.7-4.3 cm; mean,
      2.5 +/- 0.9 cm) and incomplete ablation was found in 2 (8.0%, 2/25) larger
      tumours (6.4 and 6.9 cm in diameter). No death associated with the treatment was
      found. The major complication rate was 5.5% (1/18). The follow-up periods ranged
      from 1.3 to 86.2 months (mean, 20.5 +/- 26.3 months; median, 8.7 months). OS
      rates for all patients at 6, 12, 36 and 60 months were 66.7%, 36.3%, 30.3% and
      30.3%, respectively. By univariate analysis, the patient source (primary or
      recurrent case) was found to be a significant prognostic factor for OS rates
      (p=0.001). The patient source (p=0.001) and the number of nodules (p=0.038) were
      found to be significant prognostic factors for recurrence-free survival. OS rates
      for the primary ICC at 6, 12, 36 and 60 months were 87.5%, 75.0%, 62.5% and
      62.5%, respectively. CONCLUSION: Percutaneous ultrasound-guided thermal ablation
      is a safe and effective therapeutic technique for ICC. Acceptable survival can be
      achieved in primary ICCs, whereas the prognosis of recurrent ICCs is relatively
      poor.

PMID- 22374283
TI  - Validation of motion correction techniques for liver CT perfusion studies.
AB  - OBJECTIVES: Motion in images potentially compromises the evaluation of temporally
      acquired CT perfusion (CTp) data; image registration should mitigate this, but
      first requires validation. Our objective was to compare the relative performance
      of manual, rigid and non-rigid registration techniques to correct anatomical
      misalignment in acquired liver CTp data sets. METHODS: 17 data sets in patients
      with liver tumours who had undergone a CTp protocol were evaluated. Each data set
      consisted of a cine acquisition during a breath-hold (Phase 1), followed by six
      further sets of cine scans (each containing 11 images) acquired during free
      breathing (Phase 2). Phase 2 images were registered to a reference image from
      Phase 1 cine using two semi-automated intensity-based registration techniques
      (rigid and non-rigid) and a manual technique (the only option available in the
      relevant vendor CTp software). The performance of each technique to align liver
      anatomy was assessed by four observers, independently and blindly, on two
      separate occasions, using a semi-quantitative visual validation study (employing
      a six-point score). The registration techniques were statistically compared using
      an ordinal probit regression model. RESULTS: 306 registrations (2448 observer
      scores) were evaluated. The three registration techniques were significantly
      different from each other (p=0.03). On pairwise comparison, the semi-automated
      techniques were significantly superior to the manual technique, with non-rigid
      significantly superior to rigid (p<0.0001), which in turn was significantly
      superior to manual registration (p=0.04). CONCLUSION: Semi-automated registration
      techniques achieved superior alignment of liver anatomy compared with the manual
      technique. We hope this will translate into more reliable CTp analyses.

PMID- 22374284
TI  - Three-dimensional sampling perfection with application-optimised contrasts using
      a different flip angle evolutions sequence for routine imaging of the spine:
      preliminary experience.
AB  - OBJECTIVES: The bulk of spinal imaging is still performed with conventional two
      dimensional sequences. This study assesses the suitability of three-dimensional
      sampling perfection with application-optimised contrasts using a different flip
      angle evolutions (SPACE) sequence for routine spinal imaging. METHODS: 62 MRI
      examinations of the spine were evaluated by 2 examiners in consensus for the
      depiction of anatomy and presence of artefact. We noted pathologies that might be
      missed using the SPACE sequence only or the SPACE and a sagittal T(1) weighted
      sequence. The reference standards were sagittal and axial T(1) weighted and T(2)
      weighted sequences. At a later date the evaluation was repeated by one of the
      original examiners and an additional examiner. RESULTS: There was good agreement
      of the single evaluations and consensus evaluation for the conventional
      sequences: kappa>0.8, confidence interval (CI)>0.6-1.0. For the SPACE sequence,
      depiction of anatomy was very good for 84% of cases, with high interobserver
      agreement, but there was poor interobserver agreement for other cases. For
      artefact assessment of SPACE, kappa=0.92, CI=0.92-1.0. The SPACE sequence was
      superior to conventional sequences for depiction of anatomy and artefact
      resistance. The SPACE sequence occasionally missed bone marrow oedema. In
      conjunction with sagittal T(1) weighted sequences, no abnormality was missed. The
      isotropic SPACE sequence was superior to conventional sequences in imaging
      difficult anatomy such as in scoliosis and spondylolysis. CONCLUSION: The SPACE
      sequence allows excellent assessment of anatomy owing to high spatial resolution
      and resistance to artefact. The sensitivity for bone marrow abnormalities is
      limited.

PMID- 22374285
TI  - 320-detector row CT coronary angiography: effects of heart rate and heart rate
      variability on image quality, diagnostic accuracy and radiation exposure.
AB  - OBJECTIVES: To evaluate the effects of heart rate and heart rate variability on
      image quality, patient dose and diagnostic accuracy of 320-detector row CT.
      METHODS: 94 patients were prospectively enrolled. Heart rate was defined as the
      mean value of different intervals elapsing between two consecutive R waves in an
      electrocardiogram (R-R intervals) and the heart rate variability was calculated
      as the standard deviation from the average heart rate. The image quality was
      evaluated by four grades, according to motion artefacts ("step artefacts" and
      "blurring artefacts"). The diagnostic accuracy was analysed in 43 patients who
      were scheduled for invasive coronary angiography (ICA). The coeffects of heart
      rate and heart rate variability on image quality, radiation dose and diagnostic
      accuracy were evaluated by multivariate regression. RESULTS: The mean image
      quality score was 1.2 +/- 0.5 and the mean effective dose was 14.8 +/- 9.8 mSv.
      The results showed that heart rate (74.0 +/- 11.2 beats per minute) was the
      single factor influencing image quality (p<0.001) and radiation dose (p<0.001),
      while heart rate variability (3.7 +/- 4.6) had no significant effect on them
      (p=0.16 and p=0.47, respectively). For 43 patients who underwent ICA, heart rate
      and heart rate variability showed no influence on the accuracy (p=0.17 and
      p=0.12, respectively). Overall sensitivity was 97.4% (37/38), specificity was
      99.4% (351/353), positive predictive value was 94.9% (37/39) and negative
      predictive value was 99.7% (351/352). CONCLUSION: 320-detector row CT, with
      improved longitudinal coverage of detector, resolves step artefact and high
      patient dose caused by irregular heart rate. However, it is still recommended to
      control heart rate to a lower level to eliminate blurring artefact and radiation
      dose.

PMID- 22374286
TI  - Mitral and aortic valve endocarditis caused by a rare pathogen: Streptococcus
      constellatus.
AB  - Streptococcus constellatus endocarditis is associated with systemic embolism and
      frequently with a poor prognosis. We describe the first case reported in the
      literature of infective endocarditis by penicillin-resistant S. constellatus
      causing both mitral and aortic valve regurgitation, treated successfully with
      double-valve replacement.

PMID- 22374287
TI  - Is limited pulmonary resection equivalent to lobectomy for surgical management of
      stage I non-small-cell lung cancer?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was: is limited pulmonary resection equivalent
      to lobectomy in terms of morbidity, long-term survival and locoregional
      recurrence in patients with stage I non-small-cell lung cancer (NSCLC)? A total
      of 166 papers were found using the reported search; of which, 16 papers,
      including one meta-analysis and one randomized control trial (RCT), represented
      the best evidence to answer the clinical question. The authors, journal, date and
      country of publication, patient group studied, study type, relevant outcomes and
      results of these papers are tabulated. With regards to 5-year survival rates, the
      evidence is conflicting: a 2005 meta-analysis and six other retrospective or
      prospective nonrandomized analyses did not find any statistically significant
      difference when comparing lobectomy with limited resection. However, three
      studies found evidence of a decreased overall survival with limited resection,
      including the only randomized control trial, which showed a 50% increase in the
      cancer-related death rate (P = 0.09), and a 30% increase in the overall death
      rate in patients undergoing limited resection (P = 0.08). Age, tumour size and
      specific type of limited resection were also factors influencing the survival
      rates. Four studies, including the RCT, found increased locoregional recurrence
      rates with limited resection. There is also evidence that wedge resections,
      compared with segmentectomies, lead to lower survival and higher recurrence
      rates. In conclusion, lobectomy is still recommended for younger patients with
      adequate cardiopulmonary function. Although limited resection carries a decreased
      rate of complications and shorter hospital stays, it may also carry a higher rate
      of loco-regional recurrences. However, limited resection may be comparable for
      patients >71 years of age, and those with small peripheral tumours.

PMID- 22374288
TI  - Argon plasma coagulation as an alternative treatment for bronchopleural fistulas
      developed after sleeve pneumonectomy.
AB  - We present a case that used argon plasma coagulation (APC) for the healing of
      bronchopleural fistulas (BPF), which most probably developed secondary to
      tracheobronchial anastomotic failure (TBAF). We aimed to show this procedure as
      an alternative treatment for the small fistulas that could develop after
      pneumonectomy. In a 56-year old male patient, right upper lobe squamous cell
      carcinoma was detected in 2009. Sleeve pneumonectomy was done because of the
      carina and major fissure invasion. There was no morbidity in the early post
      operative period. The patient was discharged on the seventh day without any
      problems. Three cycles of chemotherapy were applied. In the third month after
      operation, the patient complained of a cough, and odorous sputum starting 15 days
      earlier. Two fistula orifices (1 and 3 mm) were detected in the fibre-optic
      bronchoscopy (FOB). No sign of tumour recurrences was detected in either chest
      computed tomography (CT) or FOB. BPF had entered the mediastinal chamber, which
      isolated the infection from the pleural cavity. The APC procedure was applied
      using FOB under local anaesthesia. The processing time was 30 min. There were no
      complications during or after the procedure. FOB was repeated 30 days later, and
      none of the previously opened orifices were observed. The patient was followed up
      for 18 months without any symptoms. APC was generally used for the treatment of
      oesophageal and intestinal fistula. We could not find any cases in the literature
      about APC application to treat BPF. APC could be an alternative treatment for the
      selected cases with small, uncomplicated BPF.

PMID- 22374289
TI  - Surgical treatment for neonatal Ebstein's anomaly with circular shunting.
AB  - We report a case of surgical treatment for neonatal Ebstein's anomaly with
      circular shunting. A prenatal diagnosis of Ebstein's anomaly was made at 30 weeks
      of gestation. In addition to severe tricuspid regurgitation, severe pulmonary
      regurgitation was also noted, resulting in a 'circular shunt'. At 38 weeks and 2
      days of gestation, the baby was delivered by Caesarean section. A two-stage
      palliative operation was planned. As the first palliation, the pulmonary artery
      was ligated 1 h after birth to eliminate the circular shunt. Lipo-prostaglandin
      E(1) was administrated continuously to keep the ductus arteriosus patent. Four
      days after first operation, modified Starnes operation was performed as the
      second-stage palliation. The tricuspid valve was closed by an ePTFE patch with 3
      mm fenestration. Pulmonary blood flow was supplied by a right modified Blalock
      Taussig shunt with a 3.5-mm diameter ePTFE graft. The infant's postoperative
      haemodynamic status was stable. The patient is being followed up carefully and is
      scheduled to have a univentricular repair in the future.

PMID- 22374290
TI  - Abdominal compartment syndrome after endovascular repair of ruptured iliac artery
      aneurysm.
AB  - Abdominal compartment syndrome is a possible complication after aneurysm repair
      and has a high mortality rate. Although there has been an increment in patient
      survival rates after aneurysm repair, there has also been an increase in this
      entity. However, there are few data about the incidence and management of this
      complication after endovascular repair of a ruptured iliac artery aneurysm. The
      objective of this report is to describe a case of abdominal compartment syndrome
      after endovascular correction of a ruptured iliac artery aneurysm, emphasizing
      the importance of the accurate monitoring of intra-abdominal pressure, medical
      therapy and timely laparotomy. An 85-year old male was submitted to the
      endovascular repair of a ruptured iliac artery aneurysm. On the first day after
      the intervention, he developed abdominal compartment syndrome which did not
      resolve with medical therapy. Consequently, on the second postoperative day, a
      decompressive laparotomy was performed, removing the retroperitoneal haematoma,
      which was the main cause of the high intra-abdominal pressure and the abdominal
      compartment syndrome. At 12 months of follow-up, there was no evidence of
      complications. This case stresses the importance of early recognition of
      abdominal compartment syndrome.

PMID- 22374291
TI  - Use of extended radial artery conduit for complete arterial revascularization.
AB  - We have developed a new technique to elongate the radial artery (RA) with the
      distal segment of the left internal thoracic artery (LITA). The left anterior
      descending (LAD) artery is examined to define the site of the LITA-LAD
      anastomosis and the length of LITA required to perform the anastomosis. The
      distal segment of the LITA beyond this length is divided in order to elongate the
      RA. This extended conduit is long enough to perform complete arterial
      revascularization and to reach the ascending aorta for the proximal anastomosis.
      Between January 1998 and December 2010, 113 patients were operated on using this
      technique. There was no early mortality among the whole group. Two patients
      (1.8%) had perioperative myocardial infarction. Three patients (3.5%) had re
      interventions. We conclude that this technique makes the optimal use of both
      arterial conduits and could be a valuable alternative option for patients who are
      selected for complete arterial revascularization.

PMID- 22374292
TI  - Thymectomy for thymoma and myasthenia gravis. A survey of current surgical
      practice in thymic disease amongst EACTS members.
AB  - Thymic disorders, both oncological and non-oncological, are rare. Multi
      institutional, randomized studies are currently not available. The Thymic Working
      Group of the European Association for Cardio-Thoracic Surgery (EACTS) decided to
      perform a survey aiming to estimate the extent and type of current surgical
      practice in thymic diseases. A questionnaire was addressed to the thoracic and
      cardio-thoracic members of the society, and the answers received from 114
      participants were analysed. High-volume surgeons cooperate more frequently with a
      dedicated neurologist and anaesthesist (P = 0.04), determine more frequently
      neurological scores pre- and postoperatively (P = 0.02) and do not operate on
      thymic hyperplasia in stage I myasthenia gravis (MG) (P = 0.04). High-volume
      thymoma surgeons more often use a transpleural approach for stage I thymoma < 4
      cm (P = 0.01), induction therapy (P = 0.05) and are more likely to have access to
      a tissue bank (P = 0.04). Both in thymoma and MG surgery, cooperative prospective
      studies seem to be feasible in dedicated thoracic surgical associations as EACTS.

PMID- 22374293
TI  - Aspergillus endocarditis: a case of near complete left ventricular outflow
      obstruction.
AB  - A 60-year old woman presented with dyspnoea and fatigue. She was frail and
      cachectic (BMI 17.5) with a pancytopenia. Previously she had received
      chemotherapy for chronic lymphatic leukaemia. She relapsed one year ago
      necessitating a reduced intensity conditioning allogeneic haematopoietic cell
      transplantation. Subsequently, graft versus host disease required high-dose
      immunosuppressants. Computerized tomography on admission showed bilateral lung
      nodules and a suspicious cardiac mass. Bronchial biopsies demonstrated abundant
      hypae consistent with Aspergillus fumigatus infection. Echocardiography
      demonstrated a large fungus ball attached to the right coronary cusp of the
      aortic valve with near complete obliteration of the left ventricular outflow
      tract. Due to the high risk of embolization this was resected under
      cardiopulmonary bypass. The mass was attached subvalvularly to the ventricular
      septal free wall and eroding through it. It peeled off leaving intact aortic
      leaflets. Unresectable fungal deposits were discovered on the interventricular
      septum, the left ventricle free wall and posterior aortic wall. High-dose
      systemic antifungal therapy (Voriconazole and Amphoteracin B) was given for 4
      months. After discharge she remained well till a 4-month follow-up, after which
      she eventually succumbed to her disease. We discuss the clinical difficulties in
      managing patients with fungal infective endocarditis and present a brief review
      of cardiac aspergillosis management.

PMID- 22374294
TI  - Survival impact of node zone classification in resected pathological N2 non-small
      cell lung cancer.
AB  - We assessed the prognostic value of the 'Zone-classification' which has been
      proposed by the Japanese Association for Lung Cancer (JALC) for mediastinal nodal
      metastases in non-small cell lung cancer (NSCLC). Among 357 NSCLC patients who
      underwent curative surgery, 46 patients with pathological (p) N2 disease were
      divided into two groups as follows: 32 patients in whom the nearer zone was
      involved were classified as the pN2a-1 group, and 14 patients in whom the further
      mediastinal node station was involved were classified as the pN2a-2 group. The
      proportions of patients with non-adenocarcinoma histology, with multiple station
      metastases with the involvement of four or more nodes, and who underwent
      pneumonectomy, were higher in the pN2a-2 group. The 'Zone-classification' proved
      to be a significant prognostic factor in a univariate analysis (the 5-year
      overall survival rate, 7.1% for pN2a-2 versus 21.9% for pN2a-1; P < 0.01). A
      multivariate analysis confirmed that pN2a-2 sub-classification (hazard ratio
      2.77; P = 0.03) and undergoing pneumonectomy (hazard ratio 4.86; P < 0.01) were
      independent and significant factors in predicting a poor prognosis. In pN2 NSCLC
      patients, the involved mediastinal zone according to the primary tumour site was
      important in prediction of survival.

PMID- 22374295
TI  - Three-dimensional ordered macroporous bismuth vanadates: PMMA-templating
      fabrication and excellent visible light-driven photocatalytic performance for
      phenol degradation.
AB  - Three-dimension ordered macroporous (3D-OM) bismuth vanadates with a monoclinic
      crystal structure and high surface area (18-24 m(2) g(-1)) have been prepared
      using ascorbic acid (AA)- or citric acid (CA)-assisted poly(methyl methacrylate)
      (PMMA)-templating strategy with bismuth nitrate and ammonium metavanadate as the
      metal sources, HNO(3) as the pH adjuster and ethylene glycol and methanol as the
      solvent. The materials were characterized by a number of analytical techniques.
      The photocatalytic performance of the porous BiVO(4) samples was evaluated for
      the degradation of phenol in the presence of a small amount of H(2)O(2) under
      visible light illumination. The effects of the initial phenol concentration and
      the H(2)O(2) amount on the photocatalytic activity of the photocatalyst were
      examined. It is shown that the chelating agent, AA or CA, and the amount in which
      it is added had a significant impact on the quality of the 3D-OM structure, with
      a "(Bi + V):chelating agent" molar ratio of 2:1 being the most appropriate. Among
      the as-prepared BiVO(4) samples, the one with a surface area of ca. 24 m(2) g(-1)
      showed the best visible light-driven photocatalytic performance for phenol
      degradation (phenol conversion = ca. 94% at phenol concentration = 0.1 mmol L(-1)
      and in the presence of 0.6 mL H(2)O(2)). A higher phenol conversion could be
      achieved within the same reaction time if the phenol concentration in the aqueous
      solution was lowered, but an excess amount of H(2)O(2) was not a favorable factor
      for the enhancement of the catalytic activity. It is concluded that the excellent
      photocatalytic activity of 3D-OM BiVO(4) is due to the high quality 3D-OM
      structured BiVO(4) that has a high surface area and surface oxygen vacancy
      density. We are sure that the 3D-OM material is a promising photocatalyst for the
      removal of organics from wastewater under visible light illumination.

PMID- 22374297
TI  - Phosphate removal from synthetic and real wastewater using steel slags produced
      in Europe.
AB  - Electric arc furnace steel slags (EAF-slags) and basic oxygen furnace steel slags
      (BOF-slags) were used to remove phosphate from synthetic solutions and real
      wastewater. The main objective of this study was to establish an overview of the
      phosphate removal capacities of steel slags produced in Europe. The influences of
      parameters, including pH, and initial phosphate and calcium concentrations, on
      phosphate removal were studied in a series of batch experiments. Phosphate
      removal mechanisms were also investigated via an in-depth study. The maximum
      capacities of phosphate removal from synthetic solutions ranged from 0.13 to 0.28
      mg P/g using EAF-slags and from 1.14 to 2.49 mg P/g using BOF-slags. Phosphate
      removal occurred predominantly via the precipitation of Ca-phosphate complexes
      (most probably hydroxyapatite) according to two consecutive reactive phases:
      first, dissolution of CaO-slag produced an increase in Ca(2+) and OH(-) ion
      concentrations; then the Ca(2+) and OH(-) ions reacted with the phosphates to
      form hydroxyapatite. It was found that the release of Ca(2+) from slag was not
      always enough to enable hydroxyapatite precipitation. However, our results
      indicated that the Ca(2+) content of wastewater represented a further source of
      Ca(2+) ions that were available for hydroxyapatite precipitation, thus leading to
      an increase in phosphate removal efficiencies.

PMID- 22374298
TI  - Pyrosequencing reveals highly diverse microbial communities in microbial
      electrolysis cells involved in enhanced H2 production from waste activated
      sludge.
AB  - Renewable H(2) production from a plentiful biomass, waste activated sludge (WAS),
      can be achieved by fermentation, but the yields are low. The use of a microbial
      electrolysis cell (MEC) can increase the H(2) production yields to several times
      that of fermentation. We have proved that the enhancement of H(2) production was
      due to the ability of MECs to use a wider range of organic matter in WAS than in
      fermentation. To support this result strongly, we here investigated the microbial
      community structures of WAS and anode biofilms in WAS-fed MECs. A pyrosequencing
      analysis based on the bacterial 16S rRNA gene showed that dominant populations in
      MECs were more diverse than those in WAS (inoculum and substrate) after
      enrichment, and there was a clear distinction between MECs and WAS in microbial
      community structure. Diverse acid-producing bacteria and exoelectrogens
      (predominance of Geobacter) were detected in MECs but they were only rarely found
      in WAS. It has been reported that these acid-producing bacteria can ferment
      various sugars and amines with acetate, propionate, and butyrate as their major
      by-products. This was consistent with our chemical analyses. Detected
      exoelectrogens are known to use these organic acids (mainly acetate) and certain
      sugars to directly produce current for H(2) generation at the cathodes in the
      MECs. Using quantitative real-time PCR, we demonstrated that a consistent feed of
      alkaline-pretreated WAS containing large amounts of acetate led to a predominance
      of acetoclastic methanogens, while hydrogenotrophic methanogens were abundant in
      MECs fed both raw and alkaline-pretreated WAS. Syntrophic interactions between
      phylogenetically diverse microbial populations in anodophilic biofilms were found
      to drive the efficient cascade utilization of organic matter in WAS.

PMID- 22374299
TI  - Biological removal of pharmaceuticals and personal care products during
      laboratory soil aquifer treatment simulation with different primary substrate
      concentrations.
AB  - Pharmaceuticals and personal care products (PPCPs) have been detected in bodies
      of water worldwide, yet their effects on the environment are not fully
      understood. Recent toxicity studies suggest that mixtures of PPCPs at low
      concentrations may be detrimental to exposed organisms, highlighting the need to
      remove PPCPs from wastewater treatment plant effluent before it is discharged to
      the environment. In this study, the utility of biofilm-based PPCP removal as a
      means to prevent environmental PPCP contamination was investigated. The removal
      of 14 PPCPs, each at an initial concentration of 10 MUg/L, was studied in
      laboratory sand columns inoculated with wastewater treatment plant effluent. The
      examined PPCPs included biosol, biphenylol, p-chloro-m-cresol, p-chloro-m
      xylenol, chlorophene, sodium diclofenac, gabapentin, gemfibrozil, 5-fluorouracil,
      ibuprofen, ketoprofen, naproxen, triclosan, and valproic acid. Ten of the PPCPs
      were removed by greater than 95% during column passage, while the four other
      compounds proved more recalcitrant. The effect of the concentration (either 50 or
      1000 MUg/L) of an easily degradable primary substrate (acetate) supplied along
      with the mixture of PPCPs was examined. Most of the tested PPCPs were removed
      consistently by the biofilms regardless of the concentration of acetate, although
      the extent of removal for three compounds showed dependence on acetate
      concentration, and two behaved with no reproducible pattern over time. Biofilm
      protein measurements indicated that the mixture of PPCPs supplied to columns
      suppressed biofilm growth, suggesting toxicity of the PPCPs to the biofilm
      communities. This laboratory-scale experiment suggests that biofilm-based water
      treatment strategies, such as soil aquifer treatment and slow sand filtration,
      may be well-suited for the removal of many PPCPs from impacted water.

PMID- 22374300
TI  - Modelling aerobic biodegradation in vertical flow sand filters: impact of
      operational considerations on oxygen transfer and bacterial activity.
AB  - Oxygen renewal, as a prominent phenomenon for aerobic bacterial activity, deeply
      impacts Vertical Flow Constructed Wetland (VFCW) treatment efficiency. We
      introduce a multiphase model able to simulate multi-component transfer in VFCWs.
      It is based on a two-phase flow module, and a transport module. The flow module
      can quantify both water and air velocities throughout the filter during
      operation. The reactive transport module follows dissolved and gaseous oxygen
      concentrations, and the transport of solutes such as ammonium and readily
      biodegradable COD (Chemical Oxygen Demand). The consumption of components is
      governed by Monod-type kinetics. Heterotrophic and autotrophic bacteria, which
      are responsible for COD and ammonium degradation respectively, are part of the
      model components. The kinetics are based on the Constructed Wetlands Model 1. The
      results from the simulation tool were compared with existing experimental data,
      and two kinds of operation with VFCWs were investigated. The authors show strong
      interplay between oxygen renewal and bacterial consumption in case of sequential
      batch feeding with transient flooding of surface. Oxygen renewal is essentially
      convection mediated in such operation, while convection is not significant in non
      flooding operation. Simulated bacterial patterns are impacted by the operation,
      both quantitatively and spatially. From a modelling point of view, the authors
      highlight some limitations of the biological model: the description of bacterial
      lysis processes needs to be enhanced, as well as ammonium adsorption to organic
      matter.

PMID- 22374301
TI  - Secondary effects of anion exchange on chloride, sulfate, and lead release:
      systems approach to corrosion control.
AB  - Water treatment processes can cause secondary changes in water chemistry that
      alter finished water quality including chloride, sulfate, natural organic matter
      (NOM), and metal release. Hence, the goal of this research was to provide an
      improved understanding of the chloride-to-sulfate mass ratio (CSMR) with regards
      to chloride and sulfate variations at full-scale water treatment plants and
      corrosion potential under simulated premise plumbing conditions. Laboratory
      corrosion studies were conducted using Pb-Sn solder/Cu tubing galvanic cells
      exposed to model waters with low (approx. 5 mg/L Cl(-) and 10 mg/L SO(4)(2-)) and
      high (approx. 50 mg/L Cl(-) and 100 mg/L SO(4)(2-)) concentrations of chloride
      and sulfate at a constant CSMR of ~ 0.5. The role of NOM during corrosion was
      also evaluated by changing the type of organic material. In addition, full-scale
      sampling was conducted to quantify the raw water variability of chloride,
      sulfate, and NOM concentrations and the changes to these parameters from magnetic
      ion exchange treatment. Test conditions with higher concentrations of chloride
      and sulfate released significantly more lead than the lower chloride and sulfate
      test waters. In addition, the source of NOM was a key factor in the amount of
      lead released with the model organic compounds yielding significantly less lead
      release than aquatic NOM.

PMID- 22374302
TI  - Lysophosphatidic acid activates TGFBIp expression in human corneal fibroblasts
      through a TGF-beta1-dependent pathway.
AB  - Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease caused
      by a R124H point mutation in the transforming growth factor-beta-induced gene
      (TGFBI). However, the cellular role of TGFBI and the regulatory mechanisms
      underlying corneal dystrophy pathogenesis are still poorly understood.
      Lysophosphatidic acid (LPA) refers to a small bioactive phospholipid mediator
      produced in various cell types, and binds G protein-coupled receptors to enhance
      numerous biological responses, including cell growth, inflammation, and
      differentiation. LPA levels are elevated in injured cornea and LPA is involved in
      proliferation and wound healing of cornea epithelial cells. Accumulating evidence
      has indicated a crucial role for LPA-induced expression of TGFBI protein (TGFBIp)
      through secretion of transforming growth factor-beta1 (TGF-beta1). In the current
      study, we demonstrate that LPA induces TGFBIp expression in corneal fibroblasts
      derived from normal or GCD2 patients. LPA-induced TGFBIp expression was
      completely inhibited upon pretreatment with the LPA(1/3) receptor antagonists,
      VPC32183 and Ki16425, as well as by silencing LPA(1) receptor expression with
      small hairpin RNA (shRNA) in corneal fibroblasts. LPA induced secretion of TGF
      beta1 in corneal fibroblasts, and pretreatment with the TGF-beta type I receptor
      kinase inhibitor SB431542 or an anti-TGF-beta1 neutralizing antibody also
      inhibited LPA-induced TGFBIp expression. Furthermore, we show that LPA requires
      Smad2/3 proteins for the induction of TGFBIp expression. LPA elicited
      phosphorylation of Smad2/3, and Smad3 specific inhibitor SIS3 or siRNA-mediated
      depletion of endogenous Smad2/3 abrogates LPA-induced TGFBIp expression. Finally,
      we demonstrate that LPA-mediated TGFBIp induction requires JNK activation, but
      not ERK signaling pathways. These results suggest that LPA stimulates TGFBIp
      expression through JNK-dependent activation of autocrine TGF-beta1 signaling
      pathways and provide important information for understanding the role of
      phospholipids involved in cornea related diseases.

PMID- 22374303
TI  - Regulation of C/EBPbeta and resulting functions in cells of the monocytic
      lineage.
AB  - Monocyte/macrophages play an important role in orchestrating the immune response.
      The present review refers to C/EBPbeta, which is a key transcription factor
      regulating monocytic gene expression. Following a general introduction to
      C/EBPbeta, this article focuses on activators and regulators of the C/EBPbeta
      system in monocytic cells, including differentiating agents, cytokines, and
      bacterial products as well as associated signaling pathways. Furthermore,
      C/EBPbeta target genes in monocytic cells are summarized and resulting functions
      are described, including regulation of proliferation and differentiation as well
      as orchestration of processes of mainly the innate immune response. In addition,
      a variety of disease stages are described in which a dysregulation of the
      C/EBPbeta system may be involved. A detailed knowledge of the C/EBPbeta system in
      monocytic cells may help to further understand the difference between
      inflammatory and malignant proliferation as well as additional regulatory facets
      of innate immunity.

PMID- 22374304
TI  - Signal transduction by tumor necrosis factor receptors.
AB  - Tumor necrosis factor (TNF) is a key mediator in the inflammatory response which
      is implicated in the onset of a number of diseases. Research on TNF led to the
      characterization of the largest family of cytokines known until now, the TNF
      superfamily, which exert their biological effects through the interaction with
      transmembrane receptors of the TNFR superfamily. TNF itself exerts its biological
      effects interacting with two different receptors: TNFR1 and TNFR2. TNFR1 presents
      a death domain on its intracellular region. In contrast to TNFR1, TNFR2 does not
      have a death domain. Activation of TNFR1 implies the consecutive formation of two
      different TNF receptor signalling complexes. Complex I controls the expression of
      antiapoptotic proteins that prevent the triggering of cell death processes,
      whereas Complex II triggers cell death processes. TNFR2 only signals for
      antiapoptotic reactions. However, recent evidence indicates that TNFR2 also
      signals to induce TRAF2 degradation. TRAF2 is a key mediator in signal
      transduction of both TNFR1 and TNFR2. Thus, this novel signalling pathway has two
      important implications: on one hand, it represents an auto regulatory loop for
      TNFR2; on the other hand, when this signal is triggered TNFR1 activity is
      modified so that antiapoptotic pathways are inhibited and apoptotic reactions are
      enhanced.

PMID- 22374305
TI  - Angiotensin II modulates VEGF-driven angiogenesis by opposing effects of type 1
      and type 2 receptor stimulation in the microvascular endothelium.
AB  - Vascular endothelial growth factor (VEGF) is a main stimulator of pathological
      vessel formation. Nevertheless, increasing evidence suggests that Angiotensin II
      (Ang II) can play an augmentory role in this process. We thus analyzed the
      contribution of the two Ang II receptor types, AT(1)R and AT(2)R, in a mouse
      model of VEGF-driven angiogenesis, i.e. oxygen-induced proliferative retinopathy.
      Application of the AT(1)R antagonist telmisartan but not the AT(2)R antagonist
      PD123,319 largely attenuated the pathological response. A direct effect of Ang II
      on endothelial cells (EC) was analyzed by assessing angiogenic responses in
      primary bovine retinal and immortalized rat microvascular EC. Selective
      stimulation of the AT(1)R by Ang II in the presence of PD123,319 revealed a pro
      angiogenic activity which further increased VEGF-driven EC sprouting and
      migration. In contrast, selective stimulation of the AT(2)R by either CGP42112A
      or Ang II in the presence of telmisartan inhibited the VEGF-driven angiogenic
      response. Using specific inhibitors (pertussis toxin, RGS proteins, kinase
      inhibitors) we identified G(12/13) and G(i) dependent signaling pathways as the
      mediators of the AT(1)R-induced angiogenesis and the AT(2)R-induced inhibition,
      respectively. As AT(1)R and AT(2)R stimulation displays opposing effects on the
      activity of the monomeric GTPase RhoA and pro-angiogenic responses to Ang II and
      VEGF requires activation of Rho-dependent kinase (ROCK), we conclude that the
      opposing effects of the Ang II receptors on VEGF-driven angiogenesis converge on
      the regulation of activity of RhoA-ROCK-dependent EC migration.

PMID- 22374306
TI  - Peptides with antimicrobial and anti-inflammatory activities that have
      therapeutic potential for treatment of acne vulgaris.
AB  - The pathogenesis of acne vulgaris is multifactorial involving infection of the
      pilosebaceous unit with Propionibacterium acnes and a cytokine-mediated
      inflammatory response. Five frog skin-derived antimicrobial peptides
      ([D4k]ascaphin-8, [G4K]XT-7, [T5k]temporin-DRa, brevinin-2GU, and B2RP-ERa),
      chosen for their low hemolytic activity against human erythrocytes, were assessed
      for their effects on the growth of clinical isolates of P. acnes and on the
      release of pro-inflammatory and anti-inflammatory cytokines from peripheral blood
      mononuclear (PBM) cells. All peptides inhibited the growth of P. acnes with the
      highest potency exhibited by [D4k]ascaphin-8 (minimum inhibitory concentration,
      MIC=3-12.5 MUM). Release of TNF-alpha from concanavalin A (ConA)-stimulated PBM
      cells was significantly reduced by [D4k]ascaphin-8, [G4K]XT-7, brevinin-2GU, and
      B2RP-ERa (1 and 20 MUg/ml) and by [T5k]temporin-DRa (20 MUg/ml). Release of IFN
      gamma from unstimulated PBM cells was significantly reduced by [D4k]ascaphin-8
      and brevinin-2GU (1 and 20 MUg/ml). No peptide showed significant effects on Il
      17 release. Release of the anti-inflammatory cytokines TGF-beta, IL-4, and IL-10
      from both unstimulated and ConA-treated PBM cells was significantly increased by
      [T5k]temporin-DRa and B2RP-ERa (1 and 20MUg/ml). The potent activities of
      [D4k]ascaphin-8 and [T5k]temporin-DRa in inhibiting the growth of P. acnes and
      the release of pro-inflammatory cytokines, and in stimulating the release of anti
      inflammatory cytokines suggest a possible therapeutic role in the treatment of
      acne vulgaris.

PMID- 22374307
TI  - Morphological and ultrastructural description of Pleistophora dammami sp. n.
      infecting the intestinal wall of Saurida undosquamis from the Arabian Gulf, Saudi
      Arabia.
AB  - Pleistophora dammami sp. n. is described from Saurida undosquamis from the
      Arabian Gulf in Saudi Arabia. Infection appeared as whitish cysts in the
      intestinal wall. Cysts ranged in size from 1 to 4 mm. The prevalence of the
      infection across both fish sexes was 17.5% (24/420). Two kinds of spores were
      recognized, microspores and macrospores, and each were ovoid in shape. The
      microspores measured ~2.5 * 2.0 MUm in size, while the macrospores measured ~6.0
      * 3.0 MUm. Ultrastructurally, the parasite did not form xenoma but it formed
      cysts surrounded by thick cyst wall. All stages of development as meronts,
      sporonts, sporoblast and spores occurred in the cytoplasm of the host cells
      within sporophorous vesicles. The stages of development occurred asynchronously
      and thus all stages were randomly distributed within the cysts. Meronts were
      elliptical and multinucleated, with unpaired nuclei which constantly divided
      giving rise to new sporonts. During the transition to sporonts, the border of the
      meronts increased in thickness to form dense discontinuous cell coat. Later, the
      sporont divided into sporoblast cells which gradually differentiated the typical
      organelles of the spores. In mature spores, the polar filament was arranged in 20
      24 coils in two rows either side of the posterior vacuole. All ultrastructural
      and morphological criteria indicate that the described species belongs to the
      genus Pleistophora.

PMID- 22374308
TI  - Ciliate ectoparasites (Ciliophora: Trichodinidae/Chilodonellidae) on gills of
      Carassius auratus from the Yangtze River, China, with the description of
      Trichodina luzhoues sp. n.
AB  - Three species of the genus Trichodina Ehrenberg, 1838 and one species of the
      genus Chilodonella Strand, 1926 were collected from gills of Carassius auratus.
      They are Trichodina luzhoues sp. n., Trichodina mutabilis Kazubski and Migala,
      1968, Trichodina reticulata Hirschman and Partsch, 1955, and Chilodonella
      hexasticha Kiernik, 1909. T. luzhoues sp. n. is a medium-sized trichodinid, and
      its denticles are very distinctive: the blade is narrow rhombus shaped, the
      section connecting the blade and central part is long and very thin; the section
      connecting the central part and ray is short and very thick. Ch. hexasticha is a
      new record in China.

PMID- 22374309
TI  - Correlation between decreased motor activity and dopaminergic degeneration in the
      ventrolateral putamen in monkeys receiving repeated MPTP administrations: a
      positron emission tomography study.
AB  - Parkinson's disease (PD) patients have remarkably reduced levels of dopaminergic
      biomarkers in the caudal putamen. However, the relationship between motor
      impairments and the localization of intrastriatal dopaminergic degeneration in
      monkey PD models remains unclear. To identify the striatal areas with
      dopaminergic dysfunction responsible for motor impairments, we measured changes
      in both general motor activity and in vivo dopaminergic biomarkers in three
      cynomolgus monkeys that repeatedly received 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), starting in the normal state and continuing until
      after tremor appearance. Binding of dopamine transporters (DAT) and D(2)
      receptors were measured by positron emission tomography (PET) using [(11)C]PE2I
      and [(11)C]raclopride, respectively. Region-of-interest-based regression analysis
      demonstrated the degree of general motor activity reduction to be explained by
      striatal DAT binding but not by D(2) receptor binding. Furthermore, voxel-based
      analysis revealed a significant correlation between reduced general motor
      activity and decreased DAT binding, specifically in the ventrolateral putamen,
      which corresponds to the area receiving upper body motor inputs from the primary
      motor cortex. These results suggest that specific functional deficits in PD
      models are closely related to the degeneration of dopaminergic terminals in the
      striatal subregion responsible for these functions and that the level of deficit
      is dependent on the degree of degeneration.

PMID- 22374310
TI  - Sensitivity of hip tissues contact evaluation to the methods used for estimating
      the hip joint center of rotation.
AB  - Computer-based simulations of human hip joints generally include investigating
      contacts happening among soft or hard tissues during hip movement. In many cases,
      hip movement is approximated as rotation about an estimated hip center. In this
      paper, we investigate the effect of different methods used for estimating hip
      joint center of rotation on the results acquired from hip simulation. For this
      reason, we use three dimensional models of hip tissues reconstructed from MRI
      datasets of 10 subjects, and estimate their center of rotation by applying five
      different methods (including both predictive and functional approaches). Then, we
      calculate the amount of angular and radial penetrations that happen among three
      dimensional meshes of cartilages, labrum, and femur bone, when hip is rotating
      about different estimated centers of rotation. The results indicate that hip
      simulation can be highly affected by the method used for estimating hip center of
      rotation. However, under some conditions (e.g. when Adduction or External
      Rotation are considered) we can expect to have a more robust simulation. In
      addition, it was observed that applying some methods (e.g. the predictive
      approach based on acetabulum) may result in less robust simulation, comparing to
      the other methods.

PMID- 22374311
TI  - Adiponectin relation to skin changes and dyslipidemia in systemic sclerosis.
AB  - OBJECTIVES: Adiponectin was initially described as a regulator of metabolic
      homeostases. Further studies demonstrated its involvement in the regulation of
      inflammatory diseases, particularly rheumatic and vascular diseases and some
      fibrotic processes. The aim of this study was to evaluate adiponectin in the
      circulation of patients with systemic sclerosis (SSc) and characterise its
      potential association with skin changes and SSc-related features. METHODS: Serum
      levels of adiponectin, interleukin-6 and soluble receptor for interleukin-2 (by
      ELISA), lipid levels, CRP (by turbidimetry), ANA (by immunofluorescence),
      autoantibodies of the ENA complex (by immunoblot) and urine levels of
      pyridinoline and deoxypyridinoline (by HPLC) were measured in 39 patients with
      SSc, and adiponectin levels were determined in 30 healthy controls matched by
      age, sex, and body mass index (BMI). Organ manifestations were recorded and skin
      changes were assessed using the modified Rodnan skin score. RESULTS: Adiponectin
      serum levels were similar between patients with SSc and healthy controls (median
      (IQR), 6.9 (5.9-9.1) vs. 7.8 (6.2-9.5)MUg/ml, p=0.670). Levels of serum (ln)
      adiponectin were negatively correlated with the skin score (r=-0.379, p=0.017).
      Regression analysis of the relationship between adiponectin and markers of
      interest provided two statistically significant models: A- with explanatory
      variables HDL-cholesterol, skin score, disease duration, age (R(2)=0.580); and B-
      with CRP, skin score, age (R(2)=0.550); in order of a decreasing influence.
      CONCLUSION: Based on the results of this study, it might be speculated that
      adiponectin plays a protective role in skin- and atherosclerosis-related changes
      during SSc.

PMID- 22374312
TI  - Amelogenins modulate cytokine expression in LPS-challenged cultured human
      macrophages.
AB  - Amelogenins are enamel matrix proteins with a proven ability to restore tissues
      in patients with advanced periodontitis and chronic skin wounds. To explore the
      mechanisms of action of amelogenins in wound inflammation, the in vitro effect on
      the expression of selected cell mediators involved in inflammation and tissue
      repair from human monocyte-derived macrophages was studied. Macrophages were
      treated with amelogenins in serum-enriched medium with simultaneous
      lipopolysaccharide (LPS) stimulation, for 6, 24 and 72 h, and the conditioned
      culture medium was analysed for 28 different cytokines. Amelogenin treatment
      directed the LPS-induced release of both pro- and anti-inflammatory cytokines
      towards an alternatively activated macrophage phenotype. This change in
      activation was also demonstrated by the amelogenin-induced secretion of
      alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known
      as CCL18; p<0.001), a well-documented marker of alternative activation.
      Amelogenins were also shown significantly to increase the macrophage expression
      of vascular endothelial growth factor and, to a lesser but significant extent,
      insulin-like growth factor-1 after 24h of culture. The results of the present in
      vitro study show that monocyte-derived macrophages stimulated by inflammatory
      agonist LPS respond to the treatment with amelogenins by reducing the pro
      inflammatory activity and increasing the expression of tissue repair mediators.

PMID- 22374313
TI  - Synthesis, characterization, X-ray crystallography, acetyl cholinesterase
      inhibition and antioxidant activities of some novel ketone derivatives of gallic
      hydrazide-derived Schiff bases.
AB  - Alzheimer's disease (AD) is the most common form of dementia among older people
      and the pathogenesis of this disease is associated with oxidative stress.
      Acetylcholinesterase inhibitors with antioxidant activities are considered
      potential treatments for AD. Some novel ketone derivatives of gallic hydrazide
      derived Schiff bases were synthesized and examined for their antioxidant
      activities and in vitro and in silico acetyl cholinesterase inhibition. The
      compounds were characterized using spectroscopy and X-ray crystallography. The
      ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      assays revealed that all the compounds have strong antioxidant activities. N-(1
      (5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the
      most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate
      of 77% at 100 MUM. Molecular docking simulation of the ligand-enzyme complex
      suggested that the ligand may be positioned in the enzyme's active-site gorge,
      interacting with residues in the peripheral anionic subsite (PAS) and acyl
      binding pocket (ABP). The current work warrants further preclinical studies to
      assess the potential for these novel compounds for the treatment of AD.

PMID- 22374314
TI  - Lycopene/arabinoxylan gels: rheological and controlled release characteristics.
AB  - Arabinoxylan gels exhibiting different rheological and lycopene transport
      properties were obtained by modifying the polysaccharide concentration from 3 to
      4% (w/v). The apparent lycopene diffusion coefficient decreased from 2.7 * 10-7
      to 2.4 * 10-7 cm2/s as the arabinoxylan concentration in the gel changed from 3
      to 4% (w/v). A low amount of lycopene is released by diffusion from arabinoxylan
      gels. These results indicate that arabinoxylan gels could be carriers for
      lycopene delivery in specific sites after network degradation. The possibility to
      modulate lycopene release from arabinoxylan gels makes these biomaterials
      potential candidates for the controlled delivery of biomolecules.

PMID- 22374315
TI  - Flavone enhances dengue virus type-2 (NGC strain) infectivity and replication in
      vero cells.
AB  - This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone) on
      DENV-2 infectivity in Vero cells. Virus adsorption and attachment and
      intracellular virus replication were investigated using a foci forming unit assay
      (FFUA) and quantitative RT-PCR, respectively. Addition of flavone (100 MUg/mL)
      significantly increased the number of DENV-2 foci by 35.66% +/- 1.52 and 49.66%
      +/- 2.51 when added during and after virus adsorption to the Vero cells,
      respectively. The average foci size after 4 days of infection increased by 33% +/
      2.11 and 89% +/- 2.13. The DENV-2 specific RNA copy number in the flavone
      treated infected cells increased by 6.41- and 23.1-fold when compared to the mock
      treated infected cells. Flavone (100 MUg/mL) did not promote or inhibit Vero cell
      proliferation. The CC50 value of flavone against Vero cells was 446 ug/mL. These
      results suggest that flavone might enhance dengue virus replication by acting
      antagonistically towards flavonoids known to inhibit dengue virus replication.

PMID- 22374316
TI  - Two-dimensional liquid chromatography of PDMS-PS block copolymers.
AB  - In this study, liquid chromatography at critical conditions of polystyrene (PS)
      and polydimethylsiloxane (PDMS) is used as the first dimension for the two
      dimensional analysis of polydimethylsiloxane-block-polystyrene copolymers.
      Comprehensive two-dimensional liquid chromatography with size exclusion
      chromatography as the second dimension reveals information about the molar mass
      distributions of all separated fractions from the first dimension. Furthermore,
      fractions eluting at the critical conditions were collected and subjected to
      analysis in the second dimension at the critical adsorption point of the other
      block. These fractions were analyzed by Fourier transform infrared spectroscopy
      to determine their chemical compositions. The combination of the above approaches
      and the calibration of the evaporative light scattering detector for the first
      dimension analysis yield deep insights into the molecular heterogeneity of the
      block copolymer samples. The composition of the samples and the chemical
      composition of the real block copolymer are also calculated by combining the
      results obtained at both critical conditions.

PMID- 22374317
TI  - Metabotyping of human colorectal cancer using two-dimensional gas chromatography
      mass spectrometry.
AB  - Colorectal cancer (CRC) is the fourth most common cause of death from cancer in
      the world. The limitations of the currently available methods and biomarkers for
      CRC management highlight the necessity of finding novel markers. Metabonomics can
      be used to search for potential markers that can provide molecular insight into
      human CRC. The emergence of two-dimensional gas chromatography time of flight
      mass spectrometry (GC * GC/TOFMS) has comprehensively enhanced the metabolic
      space coverage of conventional GC/MS. In this study, a GC * GC/TOFMS was
      developed for the tissue-based global metabonomic profiling of CRC. A Pegasus GC
      * GC/TOFMS (Leco Corp., St. Joseph, MI, USA) system comprising an Agilent 7890 GC
      and Pegasus IV TOFMS was used for this purpose. An Agilent DB-1 (30 m * 250 MUm *
      0.25 MUm) fused silica capillary column and a Restek Rxi(r)-17 (1 m * 100 MUm *
      0.10 MUm) fused silica capillary column were used as the primary and secondary
      columns, respectively. The method was applied for global metabonomic profiling of
      matched CRC and normal tissues (n = 63) obtained from 31 CRC patients during
      surgery. An attempt was also made to compare GC * GC/TOFMS with GC/MS and NMR in
      similar application. The results showed that the metabotype associated with CRC
      is distinct from that of normal tissue and led to the identification of
      chemically diverse marker metabolites. Metabolic pathway mapping suggested
      deregulation of various biochemical processes such as glycolysis, Krebs cycle,
      osmoregulation, steroid biosynthesis, eicosanoid biosynthesis, bile acid
      biosynthesis, lipid, amino acid and nucleotide metabolism.

PMID- 22374318
TI  - Syntheses, structures, photoluminescence, and magnetic properties of (3,6)- and 4
      connected lanthanide metal-organic frameworks with a semirigid tricarboxylate
      ligand.
AB  - Lanthanide coordination polymers [LnL(DMF)(2)].0.25H(2)O [Ln = La (1), Ce (2), Pr
      (3), Nd (4), Sm (5), Eu (6), Gd (7), Tb (8), Dy (9), Ho (10), Er (11), and Tm
      (12)], and [GdL(H(2)O)(3)] (7') (H(3)L = 5-(4-carboxy-2-nitrophenoxy)-isophthalic
      acid), have been synthesized under hydro- and solvothermal conditions,
      respectively. Compounds 1-12 exhibit the same three-dimensional (3D)
      architecture, which is built up from binuclear paddle-wheel building blocks, and
      their resulting frameworks can be rationalized as rarely reported flu-3,6-C2/c
      topology. Compound 7' crystallizes in the monoclinic system, space group P2(1)/c.
      The ligands (L) bridge the Gd(III) centers to form 3D frameworks featuring a
      zeolite BCT topology, which have been unreported based on rare earth metals until
      now. Moreover, compound 6 exhibits characteristic red luminescent properties of
      Eu(III) complexes. The magnetic susceptibilities, over a temperature range of 2.0
      300 K, of 7 and 7' have also been investigated.

PMID- 22374319
TI  - Effects of prenatal care on child health at age 5.
AB  - The broad goal of contemporary prenatal care is to promote the health of the
      mother, child, and family through the pregnancy, delivery, and the child's
      development. Although the vast majority of mothers giving birth in developed
      countries receive prenatal care, past research has not found compelling evidence
      that early or adequate prenatal care has favorable effects on birth outcomes. It
      is possible that prenatal care confers health benefits to the child that do not
      become apparent until after the perinatal period. Using data from a national
      urban birth cohort study in the US, we estimate the effects of prenatal care on
      four markers of child health at age 5-maternal-reported health status, asthma
      diagnosis, overweight, and height. Prenatal care, defined a number of different
      ways, does not appear to have any effect on the outcomes examined. The findings
      are robust and suggest that routine health care encounters during the prenatal
      period could potentially be used more effectively to enhance children's health
      trajectories. However, future research is needed to explore the effects of
      prenatal care on additional child health and developmental outcomes as well as
      the effects of preconceptional and maternal lifetime healthcare on child health.

PMID- 22374320
TI  - Deubiquitinating enzyme BAP1 is involved in the formation and maintenance of the
      diapause embryos of Artemia.
AB  - The modification of proteins by ubiquitination and deubiquitination plays an
      important role in various cellular processes. BRCA1-associated protein-1 (BAP1)
      is a deubiquitinating enzyme whose function in the control of the cell cycle
      requires both its deubiquitinating activity and nuclear localization. In the
      present study, a ubiquitin carboxyl-terminal hydrolase belonging to the BAP1
      family was identified and characterized from Artemia parthenogenetica, a member
      of a family of brine shrimp that, under certain conditions, produce and release
      diapause embryos in which cell division and turnover of macromolecules are
      arrested. Western blot analysis and in vitro enzyme activity assay revealed
      ArBAP1 to be a cytoplasmic protein with typical ubiquitin hydrolase activity.
      Northern blot analysis revealed that ArBAP1 was abundant in the abdomen of
      Artemia producing diapause-destined embryos. Furthermore, by in situ
      hybridization, ArBAP1 was located exclusively in the embryos. In vivo knockdown
      of ArBAP1 by RNA interference resulted in the formation of embryos with split
      shells and abortive nauplii. The present findings suggest that ArBAP1, the first
      reported cytoplasmic BAP1, participates in the formation of diapause embryos and
      plays an important role in the control of cell cycle arrest in these encysted
      embryos.

PMID- 22374321
TI  - Human evoked cortical activity to silent gaps in noise:  effects of age,
      attention, and cortical processing speed.
AB  - OBJECTIVES: The goal of this study was to examine the degree to which age-related
      differences in early or automatic levels of auditory processing and attention
      related processes explain age-related differences in auditory temporal
      processing. We hypothesized that age-related differences in attention and
      cognition compound age-related differences at automatic levels of processing,
      contributing to the robust age effects observed during challenging listening
      tasks. DESIGN: We examined age-related and individual differences in cortical
      event-related potential (ERP) amplitudes and latencies, processing speed, and gap
      detection from 25 younger and 25 older adults with normal hearing. ERPs were
      elicited by brief silent periods (gaps) in an otherwise continuous broadband
      noise and were measured under two listening conditions, passive and active.
      During passive listening, participants ignored the stimulus and read quietly.
      During active listening, participants button pressed each time they detected a
      gap. Gap detection (percent detected) was calculated for each gap duration during
      active listening (3, 6, 9, 12, and 15 msec). Processing speed was assessed using
      the Purdue Pegboard Test and the Connections Test. Repeated measures analyses of
      variance assessed effects of age on gap detection, processing speed, and ERP
      amplitudes and latencies. An "attention modulation" construct was created using
      linear regression to examine the effects of attention while controlling for age
      related differences in auditory processing. Pearson correlation analyses assessed
      the extent to which attention modulation, ERPs, and processing speed predicted
      behavioral gap detection. RESULTS: Older adults had significantly poorer gap
      detection and slower processing speed than younger adults. Even after adjusting
      for poorer gap detection, the neurophysiological response to gap onset was
      atypical in older adults with reduced P2 amplitudes and virtually absent N2
      responses. Moreover, individual differences in attention modulation of P2
      response latencies and N2 amplitudes predicted gap detection and processing speed
      in older adults. That is, older adults with P2 latencies that decreased and N2
      amplitudes that increased with active listening had faster processing speed and
      better gap detection than those older adults whose P2 latencies increased and N2
      amplitudes decreased with attention. CONCLUSIONS: The results from the present
      study are broadly consistent with previous findings that older adults exhibit
      significantly poorer gap detection than younger adults in challenging tasks. Even
      after adjusting for poorer gap detection, older and younger adults showed robust
      differences in their electrophysiological responses to sound offset. Furthermore,
      the degree to which attention modulated the ERP was associated with individual
      variation in measures of processing speed and gap detection. Taken together,
      these results suggest an age-related deficit in early or automatic levels of
      auditory temporal processing and that some older adults may be less able to
      compensate for declines in processing by attending to the stimulus. These results
      extend our previous findings and support the hypothesis that age-related
      differences in cognitive or attention-related processing, including processing
      speed, contribute to an age-related decrease in gap detection.

PMID- 22374322
TI  - An evaluation of indexes as support tools in the diagnosis of sleep apnea.
AB  - This article evaluates several indexes as support tools to diagnose patients with
      Sleep Apnea-Hypopnea Syndrome (SAHS). Some of these indexes, such as the Apnea
      Hypopnea Index, have been standardized and studied in depth in the literature.
      Other indexes are used extensively in the reports that commercial polysomnographs
      generate. However, they have not been studied in detail and clinicians have no
      standardized guidelines for interpreting them. Examples are the mean and maximum
      duration of apneas and hypopneas. Finally, several novel indexes proposed by the
      authors are also evaluated. To evaluate the indexes, we have used a database of
      274 patients who have undergone a polysomnographic test. Several feature
      selection techniques were used to assess the capability of each index to
      discriminate between healthy and SAHS patients. The capability of the indexes for
      diagnosing the patients was analyzed by using decision trees which were trained
      using each index individually, and all the indexes together. Our results suggest
      that some indexes which are often present in the reports of commercial
      polysomnographs provide little or no information. On the other hand, other
      indexes that are usually not considered have a great capability to discern
      between SAHS and control patients.

PMID- 22374323
TI  - Usefulness of corticosteroid therapy during chronic disseminated candidiasis:
      case reports and literature review.
AB  - OBJECTIVES: Chronic disseminated candidiasis (CDC) is a disseminated fungal
      infection that is frequently seen in patients undergoing intensive treatment of
      haematological malignancies. The first signs of CDC appear during neutrophil
      recovery. Clinical and physiopathological characteristics of CDC suggest it
      belongs to the spectrum of fungus-related immune reconstitution inflammatory
      syndrome (IRIS). We report five cases of CDC treated with antifungal therapy and
      adjuvant corticosteroids to decrease the exacerbated inflammatory response.
      METHODS: We conducted a retrospective study in the Haematology Department of the
      University Hospital of Tours, France. The five reported cases were treated for
      CDC with antifungal therapy and adjuvant corticosteroids. RESULTS: Of the five
      cases of CDC, one was proven and four were possible, according to the 2008
      European Organization for Research and Treatment of Cancer (EORTC)
      classification. All patients were being treated for acute leukaemia. In all
      cases, symptoms disappeared 2.8 days (range, 1-7) after the beginning of
      adjunctive corticosteroid therapy. Corticosteroids were administered on average
      for 146 days (range, 4 weeks-1 year) and antifungal therapy was administered for
      the duration of chemotherapy consolidation. There was no exacerbation of CDC
      symptoms during the next round of chemotherapy or bone marrow transplantation.
      One patient died from relapse of leukaemia. CONCLUSIONS: Within the framework of
      IRIS, adjuvant corticosteroid therapy could rapidly improve CDC symptoms and
      allow continued chemotherapy without delay and without compromising the
      haematological prognosis.

PMID- 22374325
TI  - The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell
      proliferation.
AB  - Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, has been
      recently taken into consideration as a promising therapeutic tool for tumor
      treatment based on its ability to stabilize and activate the p53 transcription
      factor pathway. Since Nutlin-3 displays non cell-autonomous tumor-suppressor
      activities, we wanted to investigate its effect on dendritic cell functions,
      given the central role of these cells in the modulation of the immune response.
      We found that Nutlin-3 alone slightly affected the levels of major
      histocompatibility complex and costimulatory molecules and significantly promoted
      the ability of dendritic cells to stimulate T cells in the mixed lymphocyte
      reaction. Taken together, our findings suggest that the ability of Nutlin-3 to
      modulate dendritic cell functions and therefore lymphocyte proliferation might
      represent an additional important mechanism by which Nutlin-3 exerts its non cell
      autonomous tumor-suppression function.

PMID- 22374324
TI  - Phosphorylation of myosin II regulatory light chain controls its accumulation,
      not that of actin, at the contractile ring in HeLa cells.
AB  - During cytokinesis in eukaryotic cells, an actomyosin-based contractile ring (CR)
      is assembled along the equator of the cell. Myosin II ATPase activity is
      stimulated by the phosphorylation of the myosin II regulatory light chain (MRLC)
      in vitro, and phosphorylated MRLC localizes at the CR in various types of cells.
      Previous studies have determined that phosphorylated MRLC plays an important role
      in CR furrowing. However, the role of phosphorylated MRLC in CR assembly remains
      unknown. Here, we have used confocal microscopy to observe dividing HeLa cells
      expressing fluorescent protein-tagged MRLC mutants and actin during CR assembly
      near the cortex. Di-phosphomimic MRLC accumulated at the cell equator earlier
      than non-phosphorylatable MRLC and actin. Interestingly, perturbation of myosin
      II activity by non-phosphorylatable MRLC expression or treatment with
      blebbistatin, a myosin II inhibitor, did not alter the time of actin accumulation
      at the cell equator. Furthermore, inhibition of actin polymerization by treatment
      with latrunculin A had no effect on MRLC accumulation at the cell equator. Taken
      together, these data suggest that phosphorylated MRLC temporally controls its own
      accumulation, but not that of actin, in cultured mammalian cells.

PMID- 22374326
TI  - Influence of myeloperoxidase-catalyzing reaction on the binding between
      myeloperoxidase and anti-myeloperoxidase antibodies.
AB  - In the current study, whether myeloperoxidase (MPO)-catalyzing reaction could
      influence the antigenicity of MPO was investigated. Hypochlorite acid, the main
      product of the catalytic reaction, could lower the binding between MPO
      antineutrophil cytoplasmic antibodies (ANCA) and MPO when the available chlorine
      was higher than 0.031*10(-3) g/l. After MPO-catalyzing reaction with H(2)O(2)
      lower than 0.469 g/l, the binding level between MPO-ANCAcontaining plasma and MPO
      increased slightly. The peak binding level was 1.135 +/- 0.205 (expressed by the
      absorbance value at 405 nm). However, with the existence of hydrogen donor (o
      phenylenediamine) in the reaction system, the peak binding level between MPO-ANCA
      containing plasma and post-catalyzing MPO was significantly higher (1.367 +/-
      0.321 vs 1.135 +/- 0.205, p = 0.023). Moreover, at the approximately physical
      concentration of H(2)O(2) (0.02 g/l), MPO-ANCA exhibited higher titer to post
      catalyzing MPO than to pre-catalyzing MPO (3.91 +/- 0.84 vs 3.57 +/- 0.84, p <
      0.001, expressed as the lgT). These data demonstrated that MPO-catalyzing
      reaction could potentially increase the antigenicity of MPO.

PMID- 22374327
TI  - Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease:
      case report.
AB  - von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor
      syndrome of the viscera and central nervous system (CNS). The most common tumors
      associated with this disease are histologically benign, slow-growing CNS
      hemangioblastomas affecting the retina, cerebellum, brainstem, spinal cord or
      nerve roots. With mean age at diagnosis of 30 years, CNS hemangioblastomas are
      usually the first manifestation of the disease. Ongoing clinical and radiological
      surveillance is required, with symptomatic lesions necessitating treatment. As
      tumor growth is inevitable during the lifetime of most VHL patients, and the
      multiplicity of tumors may preclude surgical cure, the search for effective
      therapies is ongoing. Here we provide the first report demonstrating clinical and
      radiological anti-tumor response using pazopanib, a small molecule multi-receptor
      tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated
      CNS hemangioblastoma. Treatment initiation with daily oral pazopanib (800 mg/day)
      resulted in significant neurologic improvement and radiologic tumor volume
      reduction.

PMID- 22374329
TI  - Oligonucleotide-templated reactions for sensing nucleic acids.
AB  - Oligonucleotide-templated reactions are useful for applying nucleic acid sensing.
      Various chemistries for oligonucleotide-templated reaction have been reported so
      far. Major scientific interests are focused on the development of signal
      amplification systems and signal generation systems. We introduce the recent
      advances of oligonucleotide-templated reaction in consideration of the above two
      points.

PMID- 22374330
TI  - Comparative brain architecture of the European shore crab Carcinus maenas
      (Brachyura) and the common hermit crab Pagurus bernhardus (Anomura) with notes on
      other marine hermit crabs.
AB  - The European shore crab Carcinus maenas and the common hermit crab Pagurus
      bernhardus are members of the sister taxa Brachyura and Anomura (together forming
      the taxon Meiura) respectively. Both species share similar coastal marine
      habitats and thus are confronted with similar environmental conditions. This
      study sets out to explore variations of general brain architecture of species
      that live in seemingly similar habitats but belong to different major
      malacostracan taxa and to understand possible differences of sensory systems and
      related brain compartments. We examined the brains of Carcinus maenas, Pagurus
      bernhardus, and three other hermit crab species with immunohistochemistry against
      tyrosinated tubulin, f-actin, synaptic proteins, RF-amides and allatostatin. Our
      comparison showed that their optic neuropils within the eyestalks display strong
      resemblance in gross morphology as well as in detailed organization, suggesting a
      rather similar potential of processing visual input. Besides the well-developed
      visual system, the olfactory neuropils are distinct components in the brain of
      both C. maenas and P. bernhardus as well as the other hermit crabs, suggesting
      that close integration of olfactory and visual information may be useful in
      turbid marine environments with low visibility, as is typical for many habitats
      such as, e.g., the Baltic and the North Sea. Comparing the shape of the olfactory
      glomeruli in the anomurans showed some variations, ranging from a wedge shape to
      an elongate morphology. Furthermore, the tritocerebrum and the organization of
      the second antennae associated with the tritocerebrum seem to differ markedly in
      C. maenas and P. bernhardus, indicating better mechanosensory abilities in the
      latter close to those of other Decapoda with long second antennae, such as
      Astacida, Homarida, or Achelata. This aspect may also represent an adaptation to
      the "hermit lifestyle" in which competition for shells is a major aspect of their
      life history. The shore crab C. maenas, on the other hand seems to rely much less
      on mechanosensory information mediated by the second antennae but in water, the
      visual and the olfactory senses seem to be the most important modalities.

PMID- 22374332
TI  - The cyclin-dependent kinase inhibitor flavopiridol potentiates doxorubicin
      efficacy in advanced sarcomas: preclinical investigations and results of a phase
      I dose-escalation clinical trial.
AB  - PURPOSE: Dysregulated cyclin-dependent kinases are important to the growth of
      some sarcomas. Flavopiridol is a pan-CDK inhibitor that has been shown to
      potentiate chemotherapy. As such, we explored the potentiation of doxorubicin by
      flavopiridol in sarcoma, in vitro and in vivo, and conducted a phase I trial of
      flavopiridol with doxorubicin in patients with advanced sarcomas. EXPERIMENTAL
      DESIGN: Sarcoma cell lines and xenografts were treated with flavopiridol alone
      and in combination with doxorubicin. In the phase I study, doxorubicin and
      flavopiridol were administered on two flavopiridol schedules; a 1-hour bolus and
      split dosing as a 30-minute bolus followed by a 4-hour infusion. RESULTS:
      Preclinically, flavopiridol potentiated doxorubicin. In vivo, doxorubicin
      administered 1 hour before flavopiridol was more active than doxorubicin alone.
      Clinically, 31 patients were enrolled on protocol and flavopiridol was escalated
      to target dose in two schedules (90 mg/m(2) bolus; 50 mg/m(2) bolus + 40 mg/m(2)
      infusion) both in combination with doxorubicin (60 mg/m(2)). Dose-limiting
      toxicities were neutropenia, leukopenia, and febrile neutropenia but no maximum
      tolerated dose was defined. Flavopiridol pharmacokinetics showed increasing
      C(max) with increasing dose. Response Evaluation Criteria in Solid Tumors
      (RECIST) responses included two partial responses, however, stable disease was
      seen in 16 patients. Of 12 evaluable patients with progressive well- and
      dedifferentiated liposarcoma, eight had stable disease greater than 12 weeks.
      CONCLUSIONS: The sequential combination of doxorubicin followed by flavopiridol
      is well tolerated on both schedules. Disease control was observed in well- and
      dedifferentiated liposarcoma specifically, a disease in which CDK4 is known to be
      amplified.

PMID- 22374331
TI  - Plasma biomarkers as predictors of outcome in patients with advanced
      hepatocellular carcinoma.
AB  - PURPOSE: Validated biomarkers of prognosis and response to drug have not been
      identified for patients with hepatocellular carcinoma (HCC). One of the
      objectives of the phase III, randomized, controlled Sorafenib HCC Assessment
      Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers
      to predict prognosis and therapeutic efficacy. EXPERIMENTAL DESIGN: In SHARP, 602
      patients with advanced HCC were randomized to receive either oral sorafenib 400
      mg twice a day per os or matching placebo daily on a continuous basis. Ten plasma
      biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at
      baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were
      analyzed to identify correlates of prognosis or predictors of response to
      sorafenib. RESULTS: In both the entire patient population and the placebo cohort,
      baseline angiopoietin 2 (Ang2) and VEGF concentrations independently predicted
      survival. Clinical variables such as macroscopic vascular invasion, Eastern
      Cooperative Oncology Group (ECOG) performance status, and baseline alpha
      fetoprotein and alkaline phosphatase concentrations also independently predicted
      survival in these groups. In the sorafenib cohort, trends toward enhanced
      survival benefit from sorafenib were observed in patients with high s-c-KIT or
      low hepatocyte growth factor concentration at baseline (P of interaction = 0.081
      and 0.073, respectively). CONCLUSIONS: The angiogenesis biomarkers Ang2 and VEGF
      were independent predictors of survival in patients with advanced HCC. In
      contrast, none of the biomarkers tested significantly predicted response to
      sorafenib.

PMID- 22374333
TI  - cMET and phospho-cMET protein levels in breast cancers and survival outcomes.
AB  - PURPOSE: To evaluate cMET (mesenchymal-epithelial transition factor gene) and
      phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival
      outcomes. EXPERIMENTAL DESIGN: We measured protein levels of cMET and p-cMET in
      257 breast cancers using reverse phase protein array. Regression tree method and
      Martingale residual plots were applied to find best cutoff point for high and low
      levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and
      overall (OS) survival. Cox proportional hazards models were fit to determine
      associations of cMET/p-cMET with outcomes after adjustment for other
      characteristics. RESULTS: Median age was 51 years. There were 140 (54.5%) hormone
      receptor (HR) positive, 53 (20.6%) HER2 positive, and 64 (24.9%) triple-negative
      tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high
      levels of cMET and p-cMET, respectively. There were no significant differences in
      mean expression of cMET (P < 0.128) and p-cMET (P < 0.088) by breast cancer
      subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor
      for RFS [HR: 2.44, 95% confidence interval (CI): 1.34-4.44, P = 0.003 and HR:
      1.64, 95% CI: 1.04-2.60, P = 0.033] and OS (HR: 3.18, 95% CI: 1.43-7.11, P =
      0.003 and HR: 1.92, 95% CI: 1.08-3.44, P = 0.025). Within breast cancer subtypes,
      high cMET levels were associated with worse RFS (P = 0.014) and OS (P = 0.006) in
      HR-positive tumors, and high p-cMET levels were associated with worse RFS (P =
      0.019) and OS (P = 0.014) in HER2-positive breast cancers. In multivariable
      analysis, patients with high cMET had a significantly higher risk of recurrence
      (HR: 2.06, 95% CI: 1.08-3.94, P = 0.028) and death (HR: 2.81, 95% CI: 1.19-6.64,
      P = 0.019). High p-cMET level was associated with higher risk of recurrence (HR:
      1.79, 95% CI: 1.08-2.95.77, P = 0.020). CONCLUSIONS: High levels of cMET and p
      cMET were seen in all breast cancer subtypes and correlated with poor prognosis.

PMID- 22374335
TI  - Comparative performance of warfarin pharmacogenetic algorithms in Chinese
      patients.
AB  - INTRODUCTION: Multiple warfarin pharmacogenetic algorithms have been confirmed to
      predict warfarin dose more accurately than clinical algorithm or the fixed-dose
      approach. However, their performance has never been objectively evaluated in
      patients under low intensity warfarin anticoagulation, which is optimal for
      prevention of thromboembolism in Asian patients. MATERIAL AND METHODS: We sought
      to compare the performances of 8 eligible pharmacogenetic algorithms in a cohort
      of Chinese patients (n=282) under low intensity warfarin anticoagulation with
      target international normalized ratio (INR) ranged from 1.6 to 2.5. The
      performance of each algorithm was evaluated by calculating the percentage of
      patients whose predicted dose fell within 20% of their actual therapeutic dose
      (percentage within 20%), and the mean absolute error (MAE) between each predicted
      dose and actual stable dose. RESULTS: In the entire cohort, the pharmacogenetic
      algorithms could predict warfarin dose with the average MAE of 0.87 +/- 0.17
      mg/day (0.73-1.17 mg/day), and the average percentage within 20% of 43.8% +/-
      8.1% (29.1% - 52.1%). By pairwise comparison, warfarin dose prediction was
      significantly more accurate with the algorithms derived from Asian patients
      (48.6% - 50.0%) than those from Caucasian patients (29.1% - 39.7%; odds ratio
      [OR]: 1.61-3.36, p <= 0.02). Algorithms with additional covariates of INR values
      or CYP4F2*3 performed better than those without the covariates (adding INR: OR:
      1.71 (1.08-2.72), p =0.029; adding CYP4F2*3: OR: 2.67(1.41-5.05), p =0.004). When
      the patients were stratified according to the dose range, the algorithms from
      Caucasian and racially mixed populations tended to perform better in higher dose
      group (>= 4.5mg/day), and algorithms from Asian populations performed better in
      intermediate dose group (1.5-4.5mg/day). None of the algorithms performed well in
      lower dose group (<= 1.5mg/day). CONCLUSIONS: No eligible pharmacogenetic
      algorithm could perform the best for all dosing range in the Chinese patients
      under low intensity warfarin anticoagulation. Construction of a refinement
      pharmacogenetic algorithm integrating 3 genotypes (CYP2C9, VKORC1 and CYP4F2) and
      INR data should be warranted to improve the warfarin dose prediction in such
      patients.

PMID- 22374334
TI  - Aurora A inhibitor (MLN8237) plus vincristine plus rituximab is synthetic lethal
      and a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma.
AB  - PURPOSE: Aurora A and B are oncogenic serine/threonine kinases that regulate
      mitosis. Overexpression of Auroras promotes resistance to microtubule-targeted
      agents. We investigated mechanistic synergy by inhibiting the mitotic spindle
      apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either
      vincristine [MV] or docetaxel [MD] in aggressive B-cell non-Hodgkin lymphoma (B
      NHL). The addition of rituximab [R] to MV or MD was evaluated for synthetic
      lethality. EXPERIMENTAL DESIGN: Aggressive B-NHL cell subtypes were evaluated in
      vitro and in vivo for target modulation and anti-NHL activity with single agents,
      doublets, and triplets by analyzing cell proliferation, apoptosis, tumor growth,
      survival, and mechanisms of response/relapse by gene expression profiling with
      protein validation. RESULTS: MV is synergistic whereas MD is additive for cell
      proliferation inhibition in B-NHL cell culture models. Addition of rituximab to
      MV is superior to MD, but both significantly induce apoptosis compared with
      doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest
      single-agent activity for MLN8237, rituximab, docetaxel, and vincristine with
      tumor growth inhibition (TGI) of approximately 10% to 15%. Of the doublets, MV
      caused tumor regression, whereas TGI was observed with MD (approximately 55%-60%)
      and MR (approximately 25%-50%), respectively. Although MV caused tumor
      regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was
      curative, whereas MDR led to TGI of approximately 85%. Proliferation cell nuclear
      antigen, Aurora B, cyclin B1, cyclin D1, and Bcl-2 proteins of harvested tumors
      confirmed response and resistance to therapy. CONCLUSIONS: Addition of rituximab
      to MV is a novel therapeutic strategy for aggressive B-NHL and warrants clinical
      trial evaluation.

PMID- 22374337
TI  - Species restriction of Herpesvirus saimiri and Herpesvirus ateles: human
      lymphocyte transformation correlates with distinct signaling properties of viral
      oncoproteins.
AB  - The potential of Herpesvirus saimiri (HVS) subgroups A, B and C and Herpesvirus
      ateles (HVA) to transform primary T cells to permanent growth in vitro is
      restricted by the primate host species and by viral variability represented by
      distinct viral oncoproteins. We now addressed the relation between the
      transforming potential of the different viruses and the signaling pathways
      activated by transiently expressed oncoproteins. Marmoset lymphocytes were
      transformed by all HVS subgroups as well as HVA, while transformation of human
      cells was restricted to HVS-C and, unexpectedly, HVA. NF-kappaB and Src-family
      kinase (SFK) activity was required for survival of all transformed lymphocytes.
      Accordingly, NF-kappaB was induced by oncoproteins of all viruses. In contrast,
      SFK-related signaling was detectable only for oncoproteins of HVS-C and HVA.
      Thus, the restricted transformation of human lymphocytes likely correlates with
      the specific SFK targeting by these oncoproteins. These results will enable
      further studies into novel SFK effector mechanisms relevant for T-cell
      proliferation.

PMID- 22374336
TI  - Venous thromboembolism in immobilized patients with dementia. Findings from the
      RIETE registry.
AB  - BACKGROUND: The natural history of venous thromboembolism (VTE) in patients with
      dementia has not been thoroughly studied. METHODS: We used the RIETE Registry
      data to assess the clinical characteristics, treatment strategies and outcome
      during the first 3 months after acute VTE in all immobilized patients with
      dementia. RESULTS: As of August 2011, 37988 patients had been enrolled, of whom
      1316 (3.5%) had dementia. Most patients in both subgroups were initially treated
      with low-molecular-weight heparin (LMWH). Then, 48% of patients with dementia and
      25% of those without dementia received LMWH as long-term therapy. During the
      first 3 months of anticoagulant therapy, patients with dementia had a higher
      incidence of fatal pulmonary embolism (PE): 4.0% vs. 1.2% (odds ratio: 3.3; 95%
      CI: 2.5-4.4) and fatal bleeding: 1.4% vs. 0.5% (odds ratio: 2.9; 95% CI: 1.8-4.6)
      than those without dementia. In demented patients initially presenting with PE,
      the incidence of fatal PE during the first week outweighed that of fatal bleeding
      (42 vs. 4 deaths), but from Day 8, the incidence of fatal PE was similar to the
      incidence of fatal bleeding. In patients initially presenting with deep vein
      thrombosis (DVT), there were 4 fatal PE and 8 fatal bleeding events. CONCLUSIONS:
      VTE patients with dementia had a high incidence of fatal PE and fatal bleeding.
      In those initially presenting with PE, the risk of dying of PE far outweighed
      that of fatal bleeding. In patients presenting with DVT alone, the risk of fatal
      PE was lower than that of fatal bleeding.

PMID- 22374339
TI  - Thermally stable rare earth dialkyl complexes supported by a novel
      bis(phosphinimine)pyrrole ligand.
AB  - A novel bis(phosphinimine)pyrrole based ligand (HL) and its synthesis are
      reported. Rare earth dialkyl complexes of the ligand, LLn(CH(2)SiMe(3))(2) (Ln =
      Er, Lu, Sc), have been prepared and found to exhibit high thermal stability in
      solution. The protio-ligand and dialkyl lanthanide complexes (Ln = Er, Lu) have
      been characterised by single crystal X-ray diffraction studies.

PMID- 22374338
TI  - Evaluation of interleukin 28B single nucleotide polymorphisms in infants
      suffering from bronchiolitis.
AB  - The genetic diversity of the host is believed to be the key of the diversity in
      the clinical presentation of bronchiolitis. The aim of this study was to
      determine whether the known rs12979860 and rs8099917 single nucleotide
      polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features
      and natural history of bronchiolitis. Both SNPs showed no significant association
      with the risk of hospitalization for respiratory syncytial virus (RSV), viral
      load, disease severity, and other clinical features of patients. Interestingly
      infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission
      than that of infants carrying CC/CT genotypes. Overall our results indicate that
      both IL28B SNPs had no impact on the clinical course of bronchiolitis with the
      only exception of the IL28B rs12979860 SNP which increased the risk of
      hospitalization for bronchiolitis at early age.

PMID- 22374340
TI  - Modeling fecundity in the presence of a sterile fraction using a semi-parametric
      transformation model for grouped survival data.
AB  - The analysis of fecundity data is challenging and requires consideration of both
      highly timed and interrelated biologic processes in the context of essential
      behaviors such as sexual intercourse during the fertile window. Understanding
      human fecundity is further complicated by presence of a sterile population, i.e.
      couples unable to achieve pregnancy. Modeling techniques conducted to date have
      largely relied upon discrete time-to-pregnancy survival or day-specific
      probability models to estimate the determinants of time-to-pregnancy or acute
      effects, respectively. We developed a class of semi-parametric grouped
      transformation cure models that capture day-level variates purported to affect
      the cycle-level hazards of conception and, possibly, sterility. Our model's
      performance is assessed using simulation and longitudinal data from one of the
      few prospective cohort studies with preconception enrollment of women followed
      for 12 menstrual cycles at risk for pregnancy. 

PMID- 22374341
TI  - Sample size determination for disease prevalence studies with partially validated
      data.
AB  - Disease prevalence is an important topic in medical research, and its study is
      based on data that are obtained by classifying subjects according to whether a
      disease has been contracted. Classification can be conducted with high-cost gold
      standard tests or low-cost screening tests, but the latter are subject to the
      misclassification of subjects. As a compromise between the two, many research
      studies use partially validated datasets in which all data points are classified
      by fallible tests, and some of the data points are validated in the sense that
      they are also classified by the completely accurate gold-standard test. In this
      article, we investigate the determination of sample sizes for disease prevalence
      studies with partially validated data. We use two approaches. The first is to
      find sample sizes that can achieve a pre-specified power of a statistical test at
      a chosen significance level, and the second is to find sample sizes that can
      control the width of a confidence interval with a pre-specified confidence level.
      Empirical studies have been conducted to demonstrate the performance of various
      testing procedures with the proposed sample sizes. The applicability of the
      proposed methods are illustrated by a real-data example.

PMID- 22374342
TI  - Spatial filtering for robust myoelectric control.
AB  - Pattern recognition techniques have been applied to extract information from
      electromyographic (EMG) signals that can be used to control electrical powered
      hand prostheses. In this paper, optimized spatial filters that enhance separation
      properties of EMG signals are investigated. In particular, different multiclass
      extensions of the common spatial patterns algorithm are applied to high-density
      surface EMG signals acquired from the forearms of ten healthy subjects.
      Visualization of the obtained filter coefficients provides insight into the
      physiology of the muscles related to the performed contractions. The CSP methods
      are compared with a commonly used pattern recognition approach in a six-class
      classification task. Cross-validation results show a significant improvement in
      performance and a higher robustness against noise than commonly used pattern
      recognition methods.

PMID- 22374343
TI  - Embedding topic discovery in conditional random fields model for segmenting
      nuclei using multispectral data.
AB  - Segmentation of cells/nuclei is a challenging problem in 2-D histological and
      cytological images. Although a large number of algorithms have been proposed,
      newer efforts continue to be devoted to investigate robust models that could have
      high level of adaptability with regard to considerable amount of image
      variability. In this paper, we propose a multiclassification conditional random
      fields (CRFs) model using a combination of low-level cues (bottom-up) and high
      level contextual information (top-down) for separating nuclei from the
      background. In our approach, the contextual information is extracted by an
      unsupervised topic discovery process, which efficiently helps to suppress
      segmentation errors caused by intensity inhomogeneity and variable chromatin
      texture. In addition, we propose a multilayer CRF, an extension of the
      traditional single-layer CRF, to handle high-dimensional dataset obtained through
      spectral microscopy, which provides combined benefits of spectroscopy and imaging
      microscopy, resulting in the ability to acquire spectral images of microscopic
      specimen. The approach is evaluated with color images, as well as spectral
      images. The overall accuracy of the proposed segmentation algorithm reaches 95%
      when applying multilayer CRF model to the spectral microscopy dataset.
      Experiments also show that our method outperforms seeded watershed, a widely used
      algorithm for cell segmentation.

PMID- 22374344
TI  - Neural network incorporating meal information improves accuracy of short-time
      prediction of glucose concentration.
AB  - Diabetes mellitus is one of the most common chronic diseases, and a clinically
      important task in its management is the prevention of hypo/hyperglycemic events.
      This can be achieved by exploiting continuous glucose monitoring (CGM) devices
      and suitable short-term prediction algorithms able to infer future glycemia in
      real time. In the literature, several methods for short-time glucose prediction
      have been proposed, most of which do not exploit information on meals, and use
      past CGM readings only. In this paper, we propose an algorithm for short-time
      glucose prediction using past CGM sensor readings and information on carbohydrate
      intake. The predictor combines a neural network (NN) model and a first-order
      polynomial extrapolation algorithm, used in parallel to describe, respectively,
      the nonlinear and the linear components of glucose dynamics. Information on the
      glucose rate of appearance after a meal is described by a previously published
      physiological model. The method is assessed on 20 simulated datasets and on 9
      real Abbott FreeStyle Navigator datasets, and its performance is successfully
      compared with that of a recently proposed NN glucose predictor. Results suggest
      that exploiting meal information improves the accuracy of short-time glucose
      prediction.

PMID- 22374345
TI  - Serum concentrations of opioids when comparing two switching strategies to
      methadone for cancer pain.
AB  - PURPOSE: Our aim was to compare pharmacological aspects of two switching
      strategies from morphine/oxycodone to methadone; the stop and go (SAG) strategy
      in which methadone is started directly after the initial opioid has been stopped,
      and the 3-days switch (3DS), in which morphine/oxycodone is gradually changed to
      methadone by cross-tapering over 3 days. METHODS: Forty-two cancer patients with
      pain and/or opioid side effects were assessed in this randomised trial. Trough
      serum concentrations of methadone, morphine, morphine-6-glucuronide (M6G), and
      oxycodone were measured on days 1, 2, 3, 4, 7, and 14. Primary outcome was number
      of patients with methadone concentrations in apparent C(SS) on day 4. Secondary
      outcomes were exposure to opioids during the first 3 days, interindividual
      variation of opioid concentrations, and correlation between methadone
      concentrations and pain intensity (PI) day 3. RESULTS: Thirty-five patients
      received methadone (16 in the SAG group, 19 in the 3DS group). The median
      preswitch morphine equivalent doses were 620 (range 350-2000) mg/day in the SAG
      group and 800 (range 90-3600) mg/day in the 3DS group (p = 0.43);42% reached
      C(SS) for methadone in the SAG group on day 4 compared with 22% in the 3DS group
      (p = 0.42). The SAG group was significantly less exposed to
      morphine/M6G/oxycodone and significantly more exposed to methadone in the first 3
      days. Methadone showed a low correlation with PI. More patients dropped out after
      intervention in the SAG group than in the 3DS group (38% vs. 5%; p = 0.032). One
      SAG patient suffered from respiratory depression on day 5. CONCLUSION: The SAG
      group was initially more exposed to methadone and less to the replaced opioids
      but without observed clinical benefit and with a higher dropout rate. Patients
      switched to methadone should be followed closely for the first 5 days, regardless
      of switching strategy.

PMID- 22374346
TI  - Comparative evaluation of three clinical decision support systems: prospective
      screening for medication errors in 100 medical inpatients.
AB  - PURPOSE: Clinical decision support systems (CDSS) are promoted as powerful
      screening tools to improve pharmacotherapy. The aim of our study was to evaluate
      the potential contribution of CDSS to patient management in clinical practice.
      METHODS: We prospectively analyzed the pharmacotherapy of 100 medical inpatients
      through the parallel use of three CDSS, namely, Pharmavista, DrugReax, and
      TheraOpt. After expert discussion that also considered all patient-specific
      clinical information, we selected apparently relevant alerts, issued suitable
      recommendations to physicians, and recorded subsequent prescription changes.
      RESULTS: For 100 patients with a median of eight concomitant drugs, Pharmavista,
      DrugReax, and TheraOpt generated a total of 53, 362, and 328 interaction alerts,
      respectively. Among those we identified and forwarded 33 clinically relevant
      alerts to the attending physician, resulting in 19 prescription changes. Four
      adverse drug events were associated with interactions. The proportion of
      clinically relevant alerts among all alerts (positive predictive value) was 5.7,
      8.0, and 7.6%, and the sensitivity to detect all 33 relevant alerts was 9.1,
      87.9, and 75.8% for Pharmavista, DrugReax and TheraOpt, respectively. TheraOpt
      recommended 31 dose adjustments, of which we considered 11 to be relevant; three
      of these were followed by dose reductions. CONCLUSIONS: CDSS are valuable
      screening tools for medication errors, but only a small fraction of their alerts
      appear relevant in individual patients. In order to avoid overalerting CDSS
      should use patient-specific information and management-oriented classifications.
      Comprehensive information should be displayed on-demand, whereas a limited number
      of computer-triggered alerts that have management implications in the majority of
      affected patients should be based on locally customized and supported algorithms.

PMID- 22374347
TI  - Indirect comparisons of treatment effects in multiple sclerosis.

PMID- 22374349
TI  - Light trapping structures in wing scales of butterfly Trogonoptera brookiana.
AB  - The fine optical structures in wing scales of Trogonoptera brookiana, a tropical
      butterfly exhibiting efficient light trapping effect, were carefully examined and
      the reflectivity was measured using reflectance spectrometry. The optimized 3D
      configuration of the coupling structure was determined using SEM and TEM data,
      and the light trapping mechanism of butterfly scales was studied. It is found
      that the front and back sides of butterfly wings possess different light trapping
      structures, but both can significantly increase the optical path and thus result
      in almost total absorption of all incident light. An optical model was created to
      check the properties of this light trapping structure. The simulated reflectance
      spectra are in concordance with the experimental ones. The results reliably
      confirm that these structures induce efficient light trapping effect. This
      functional "biomimetic structure" would have a potential value in wide
      engineering and optical applications.

PMID- 22374351
TI  - Psychosocial factors as predictors of HIV/AIDS risky behaviors among people
      living with HIV/AIDS.
AB  - Infection with the human immunodeficiency virus (HIV) that causes acquired
      immunodeficiency syndrome (AIDS) is still rising globally. In order to develop
      effective HIV/AIDS risky behavior reduction intervention strategies and to
      further decrease the spread of HIV/AIDS, it is important to assess the prevalence
      of psychosocial problems and HIV/AIDS risky behaviors in people living with
      HIV/AIDS (PLWHA). The objective of this study is to assess the relationship
      between psychosocial variables and HIV/AIDS risky behaviors among PLWHA. A total
      of 341 questionnaires were distributed and 326 were fully completed and returned,
      96% response rate. The relationships between the identified psychosocial and
      HIV/AIDS risky behaviors among PLWHA were analyzed using The Moment Structures
      software version 17.0 (SPSS Inc.) The results indicate that psychosocial health
      problems were significant predictors of HIV/AIDS risky behaviors in PLWA. Further
      cross-disciplinary research that addresses the manner in which psychosocial
      problems and HIV/AIDS risky behaviors interact with each other among PLWHA is
      needed.

PMID- 22374352
TI  - Automated motion correction for in vivo optical projection tomography.
AB  - In in vivo optical projection tomography (OPT), object motion will significantly
      reduce the quality and resolution of the reconstructed image. Based on the well
      known Helgason-Ludwig consistency condition (HLCC), we propose a novel method for
      motion correction in OPT under parallel beam illumination. The method estimates
      object motion from projection data directly and does not require any other
      additional information, which results in a straightforward implementation. We
      decompose object movement into translation and rotation, and discuss how to
      correct for both translation and general motion simultaneously. Since finding the
      center of rotation accurately is critical in OPT, we also point out that the
      system's geometrical offset can be considered as object translation and therefore
      also calibrated through the translation estimation method. In order to verify the
      algorithm effectiveness, both simulated and in vivo OPT experiments are
      performed. Our results demonstrate that the proposed approach is capable of
      decreasing movement artifacts significantly thus providing high quality
      reconstructed images in the presence of object motion.

PMID- 22374353
TI  - Analysis and correction of count rate reduction during simultaneous MR-PET
      measurements with the BrainPET scanner.
AB  - In hybrid magnetic resonance-positron emission tomography (MR-PET) studies with
      the Siemens 3T MR-BrainPET scanner an instantaneous reduction of the PET
      sensitivity was observed during execution of certain MR sequences. This
      interference was investigated in detail with custom-made as well as standard
      clinical MR sequences. The radio-frequency pulses, the switched gradient fields
      and the constant magnetic field were examined as the relevant parameters of the
      magnetic resonance imaging (MRI) system as well as the air temperature within the
      PET detectors. Our investigation comprised the analysis of the analog PET
      signals, the total count rates, the geometric distribution of the count rate
      reduction within the BrainPET detector as well as reconstructed images. The fast
      switching magnetic field gradients were identified to distort the analog PET
      detector signals. The measured count rate reduction was found to be less than 3%,
      but only up to 2% in the case of echo planar imaging sequences, as applied in
      functional MRI. For clinical sequences routinely used in hybrid MR-BrainPET
      measurements, a correction method has been designed, implemented, and evaluated .

PMID- 22374354
TI  - Confidence regions for statistical model based shape prediction from sparse
      observations.
AB  - Shape prediction from sparse observation is of increasing interest in minimally
      invasive surgery, in particular when the target is not directly visible on
      images. This can be caused by a limited field-of-view of the imaging device,
      missing contrast or an insufficient signal-to-noise ratio. In such situations, a
      statistical shape model can be employed to estimate the location of unseen parts
      of the organ of interest from the observation and identification of the visible
      parts. However, the quantification of the reliability of such a prediction can be
      crucial for patient safety. We present here a framework for the estimation of
      complete shapes and of the associated uncertainties. This paper formalizes and
      extends previous work in the area by taking into account and incorporating the
      major sources of uncertainties, in particular the estimation of pose together
      with shape parameters, as well as the identification of correspondences between
      the sparse observation and the model. We evaluate our methodology on a large
      database of 171 human femurs and synthetic experiments based on a liver model.
      The experiments show that informative and reliable confidence regions can be
      estimated by the proposed approach.

PMID- 22374355
TI  - Cell and tissue therapy regulation: worldwide status and harmonization.
AB  - Rapid developments in scientific and technological aspects in stem cell biology
      and tissue engineering have led to the increased use of human cells and tissues
      for the treatment of various diseases and injuries. The regulatory environment
      for CTT products is rapidly evolving and drug regulatory agencies are working
      towards establishment of a risk-based system with some common features. Various
      drug regulatory agencies in many countries/regions have implemented regulatory
      controls in the last few years. This article will highlight some of works done
      till date to regulate CTT products in Australia, Canada, Europe, Japan, Korea,
      Singapore and United States of America.

PMID- 22374356
TI  - Probing synaptic function in dendrites with calcium imaging.
AB  - Calcium imaging has become a widely used technique to probe neuronal activity on
      the cellular and subcellular levels. In contrast to standard electrophysiological
      methods, calcium imaging resolves sub- and suprathreshold activation patterns in
      structures as small as fine dendritic branches and spines. This review highlights
      recent findings gained on the subcellular level using calcium imaging, with
      special emphasis on synaptic transmission and plasticity in individual spines.
      Since imaging allows monitoring activity across populations of synapses, it has
      recently been adopted to investigate how dendrites integrate information from
      many synapses. Future experiments, ideally carried out in vivo, will reveal how
      the dendritic tree integrates and computes afferent signals. For example, it is
      now possible to directly test the concept that dendritic inputs are clustered and
      that single dendrites or dendritic stretches act as independent computational
      units.

PMID- 22374357
TI  - Chronic calcium imaging in neuronal development and disease.
AB  - Neuronal circuits develop, adjust to experience and degenerate in response to
      injury or disease in the course of weeks and months. Available recording
      techniques, however, typically sample physiological properties of identified
      neurons on the time scale of minutes and hours. Thus, in order to obtain a full
      understanding of a long term physiological process data need to be extrapolated
      from numerous experimental sessions and animals, often collected blindly and
      under variable conditions. The generation and ongoing engineering of genetically
      encoded calcium indicators creates an opportunity to repeatedly record activity
      from the same individual neurons in vivo over weeks, months and potentially the
      entire lifetime of a model organism. Chronic calcium imaging with genetically
      encoded indicators thus may allow to establish functional biographies of
      identified neuronal cell types in the brain and to reveal the physiological
      relevance of structural changes as they occur under natural and pathological
      conditions.

PMID- 22374358
TI  - Phylogenetic analysis of alkaline proteinase producing fluorescent pseudomonads
      associated with green gram (Vigna radiata L.) rhizosphere.
AB  - Fifty fluorescent pseudomonads were isolated from rhizospheric soil of green gram
      from nearby area of Kaziranga, Assam, India and assayed for their extracellular
      proteinase production. Out of these isolates, 20 were found to be prominent in
      proteinase production. Genetic diversity of the 20 isolates were analyzed through
      BOX-PCR fingerprinting and 16S rDNA-RFLP along with three reference strains,
      viz., Pseudomonas fluorescens (NCIM2099(T)), Pseudomonas aureofaciens
      (NCIM2026(T)), and Pseudomonas aeruginosa (MTCC2582(T)). BOX-PCR produced two
      distinct clusters at 56% similarity coefficient and seven distinct BOX profiles.
      16S rDNA-RFLP with three tetra-cutters restriction enzymes (HaeIII, AluI, and
      MspI) revealed two major clusters A and B; cluster A contained only single
      isolate FPS9 while the rest of 22 isolates belonged to the cluster B. Based on
      phenotypic characters and 16S rDNA sequence similarity, all the eight highly
      proteinase-producing strains were affiliated with P. aeruginosa. The proteinase
      was extracted from two most prominent strains (KFP1 and KFP2), purified by a
      three-step process involving (NH(4))(2)SO(4) precipitation, gel filtration, and
      ion exchange chromatography. The enzyme had an optimal pH of 8.0 and exhibit
      highest activity at 60 degrees C and 37 degrees C by KFP1 and KFP2 respectively.
      The specific activities were recorded as 75,050 (for KFP1) and 81,320 U/mg (for
      KFP2). The purified enzyme was migrated as a single band on native and SDS-PAGE
      with a molecular mass of 32 kDa. Zn(2+), Cu(2+), and Ni(2+) ion inhibited the
      enzyme activity. Enzyme activity was also inhibited by EDTA established as their
      metallo-proteinase nature.

PMID- 22374359
TI  - Collaborative sensing in a distributed PTZ camera network.
AB  - The performance of dynamic scene algorithms often suffers because of the
      inability to effectively acquire features on the targets, particularly when they
      are distributed over a wide field of view. In this paper, we propose an
      integrated analysis and control framework for a pan, tilt, zoom (PTZ) camera
      network in order to maximize various scene understanding performance criteria
      (e.g., tracking accuracy, best shot, and image resolution) through dynamic camera
      to-target assignment and efficient feature acquisition. Moreover, we consider the
      situation where processing is distributed across the network since it is often
      unrealistic to have all the image data at a central location. In such situations,
      the cameras, although autonomous, must collaborate among themselves because each
      camera's PTZ parameter entails constraints on the others. Motivated by recent
      work in cooperative control of sensor networks, we propose a distributed
      optimization strategy, which can be modeled as a game involving the cameras and
      targets. The cameras gain by reducing the error covariance of the tracked targets
      or through higher resolution feature acquisition, which, however, comes at the
      risk of losing the dynamic target. Through the optimization of this reward-versus
      risk tradeoff, we are able to control the PTZ parameters of the cameras and
      assign them to targets dynamically. The tracks, upon which the control algorithm
      is dependent, are obtained through a consensus estimation algorithm whereby
      cameras can arrive at a consensus on the state of each target through a
      negotiation strategy. We analyze the performance of this collaborative sensing
      strategy in active camera networks in a simulation environment, as well as a real
      life camera network.

PMID- 22374360
TI  - Wavelet-based compressed sensing using a Gaussian scale mixture model.
AB  - While initial compressed sensing (CS) recovery techniques operated under the
      implicit assumption that the sparse domain coefficients are independently
      distributed, recent results have indicated that integrating a statistical or
      structural dependence model of sparse domain coefficients into CS enhances
      recovery. In this paper, we present a method for exploiting empirical dependences
      among wavelet coefficients during CS recovery using a Bayes least-square Gaussian
      scale-mixture model. The proposed model is successfully incorporated into several
      recent CS algorithms, including reweighted  l(1)  minimization (RL1), iteratively
      reweighted least squares, and iterative hard thresholding. Extensive experiments
      including comparisons with a state-of-the-art model-based CS method demonstrate
      that the proposed algorithms are highly effective at reducing reconstruction
      error and/or the number of measurements required for a desired reconstruction
      quality.

PMID- 22374361
TI  - Self-crossing detection and location for parametric active contours.
AB  - Active contours are very popular tools for video tracking and image segmentation.
      Parameterized contours are used due to their fast evolution and have become the
      method of choice in the Sobolev context. Unfortunately, these contours are not
      easily adaptable to topological changes, and they may sometimes develop
      undesirable loops, resulting in erroneous results. To solve such topological
      problems, one needs an algorithm for contour self-crossing detection. We propose
      a simple methodology via simple techniques from differential topology. The
      detection is accomplished by inspecting the total net change of a given contour's
      angle, without point sorting and plane sweeping. We discuss the efficient
      implementation of the algorithm. We also provide algorithms for locating
      crossings by angle considerations and by plotting the four-connected lines
      between the discrete contour points. The proposed algorithms can be added to any
      parametric active-contour model. We show examples of successful tracking in real
      world video sequences by Sobolev active contours and the proposed algorithms and
      provide ideas for further research.

PMID- 22374363
TI  - A multiplicative iterative algorithm for box-constrained penalized likelihood
      image restoration.
AB  - Image restoration is a computationally intensive problem as a large number of
      pixel values have to be determined. Since the pixel values of digital images can
      attain only a finite number of values (e.g., 8-bit images can have only 256 gray
      levels), one would like to recover an image within some dynamic range. This leads
      to the imposition of box constraints on the pixel values. The traditional
      gradient projection methods for constrained optimization can be used to impose
      box constraints, but they may suffer from either slow convergence or repeated
      searching for active sets in each iteration. In this paper, we develop a new box
      constrained multiplicative iterative (BCMI) algorithm for box-constrained image
      restoration. The BCMI algorithm just requires pixelwise updates in each
      iteration, and there is no need to invert any matrices. We give the convergence
      proof of this algorithm and apply it to total variation image restoration
      problems, where the observed blurry images contain Poisson, Gaussian, or salt-and
      pepper noises.

PMID- 22374362
TI  - Binned progressive quantization for compressive sensing.
AB  - Compressive sensing (CS) has been recently and enthusiastically promoted as a
      joint sampling and compression approach. The advantages of CS over conventional
      signal compression techniques are architectural: the CS encoder is made signal
      independent and computationally inexpensive by shifting the bulk of system
      complexity to the decoder. While these properties of CS allow signal acquisition
      and communication in some severely resource-deprived conditions that render
      conventional sampling and coding impossible, they are accompanied by rather
      disappointing rate-distortion performance. In this paper, we propose a novel
      coding technique that rectifies, to a certain extent, the problem of poor
      compression performance of CS and, at the same time, maintains the simplicity and
      universality of the current CS encoder design. The main innovation is a scheme of
      progressive fixed-rate scalar quantization with binning that enables the CS
      decoder to exploit hidden correlations between CS measurements, which was
      overlooked in the existing literature. Experimental results are presented to
      demonstrate the efficacy of the new CS coding technique. Encouragingly, on some
      test images, the new CS technique matches or even slightly outperforms JPEG.

PMID- 22374364
TI  - Trends in life expectancy with care needs based on long-term care insurance data
      in Japan.
AB  - BACKGROUND: Using a previously developed method for calculating expected years of
      life with care needs based on data from the Japanese long-term care insurance
      system, we examined recent trends in expected years of life with care needs by
      age group and prefecture. METHODS: Information on care needs was available from
      the long-term care insurance system of Japan. Expected years of life with care
      needs by age group and prefecture in 2005-2009 were calculated. RESULTS: Expected
      years of life with care needs at age 65 increased from 1.43 years in 2005 to 1.62
      years in 2009 for men, and from 2.99 to 3.44 years for women. As a proportion of
      total life expectancy, these values show an increase from 7.9% to 8.6% in men and
      from 12.9% to 14.4% in women. Expected years with care needs did not increase in
      the age groups of 65 to 69 and 70 to 74 years but markedly increased in the age
      group of 85 years or older. Expected years with care needs increased in every
      prefecture during the period studied. The difference in 2005 between the 25th and
      75th percentiles in prefectural distributions was 0.16 years for men and 0.35
      years for women. The difference remained nearly constant between 2005 and 2009.
      CONCLUSIONS: Expected number of years of life with care needs increased among
      Japanese from 2005 to 2009, and there was a wide range in distribution among
      prefectures. Further studies on coverage of care needs under the long-term
      insurance program are necessary.

PMID- 22374365
TI  - Epidemiology of hypertension in Serbia: results of a National Survey.
AB  - BACKGROUND: We evaluated the prevalence of high blood pressure and the level of
      awareness, treatment, and control of hypertension in a Serbian population.
      METHODS: A cross-sectional study of an adult population was carried out across
      Serbia in 2006. The study involved 14 204 adults aged 20 years or older.
      Interviews and measurements of blood pressure were performed at participants'
      homes. RESULTS: Overall, 47% of the Serbian adult population had hypertension:
      25.3% had stage 1 hypertension and 18.1% had stage 2 hypertension. Only 58.0% of
      the hypertensive population were aware that they had the disease, and 60.4% were
      receiving medical treatment. Among those receiving medical treatment, only 20.9%
      had a blood pressure within the normal range. One in 10 participants with
      hypertension were not treated because, among other reasons, they thought
      treatment was unnecessary (55.3%) or they lacked money for medication (19.3%).
      CONCLUSIONS: The prevalence of undiagnosed and untreated hypertension is high in
      the adult population of Serbia. Further action is required to hasten detection
      and treatment of high blood pressure. Attention should be directed toward
      educational programs that improve knowledge, attitudes, and awareness of
      hypertension among adults.

PMID- 22374366
TI  - Health and Demographic Surveillance System in the Western and coastal areas of
      Kenya: an infrastructure for epidemiologic studies in Africa.
AB  - BACKGROUND: The Health and Demographic Surveillance System (HDSS) is a
      longitudinal data collection process that systematically and continuously
      monitors population dynamics for a specified population in a geographically
      defined area that lacks an effective system for registering demographic
      information and vital events. METHODS: HDSS programs have been run in 2 regions
      in Kenya: in Mbita district in Nyanza province and Kwale district in Coast
      Province. The 2 areas have different disease burdens and cultures. Vital events
      were obtained by using personal digital assistants and global positioning system
      devices. Additional health-related surveys have been conducted bimonthly using
      various PDA-assisted survey software. RESULTS: The Mbita HDSS covers 55,929
      individuals, and the Kwale HDSS covers 42 585 individuals. In the Mbita HDSS, the
      life expectancy was 61.0 years for females and 57.5 years for males. Under-5
      mortality was 91.5 per 1000 live births, and infant mortality was 47.0 per 1000
      live births. The total fertility rate was 3.7 per woman. Data from the Kwale HDSS
      were not available because it has been running for less than 1 year at the time
      of this report. CONCLUSIONS: Our HDSS programs are based on a computer-assisted
      survey system that provides a rapid and flexible data collection platform in
      areas that lack an effective basic resident registration system. Although the
      HDSS areas are not representative of the entire country, they provide a base for
      several epidemiologic and social study programs, and for practical community
      support programs that seek to improve the health of the people in these areas.

PMID- 22374367
TI  - Protocol for the Women And Their Children's Health (WATCH) study: a cohort of
      pregnancy and beyond.
AB  - BACKGROUND: The developmental origins of health and disease is a conceptual
      framework that helps explain the links between our early life exposures and later
      health outcomes, and is a burgeoning field of research. In this report, we
      describe the study protocol used in a prospective cohort of women recruited
      during pregnancy, with postnatal follow-up of the mothers and offspring. METHODS:
      The Women And Their Children's Health (WATCH) cohort (n = 180 women) is being
      conducted at the John Hunter Hospital, Australia (from June 2006). Women attended
      study visits during pregnancy at 19, 24, 30, and 36 weeks' gestation. Postnatal
      follow-up of the women and their offspring occurred at 3-month intervals during
      the first year after birth and annually thereafter, until age 4 years. Fetal
      ultrasound scans were performed at each pregnancy visit. Pregnancy and birth data
      were obtained from hospital records. Data collection has included maternal and
      child anthropometric, biochemical, dietary, physical activity, socioeconomic,
      medical, and other variables. CONCLUSIONS: The 2 most novel components of our
      prospective cohort study are (1) the regular and systematic tracking of fetal and
      child growth and body composition, starting in the second trimester of pregnancy
      and continuing to age 4 years, and (2) the detailed maternal and child dietary
      data collection, including biochemical parameters. Detailed cohorts that collect
      data on the early nutritional, physiological, and social determinants of health
      are valuable. Despite its relatively small sample size, many hypotheses on
      developmental origins can be tested or piloted using data collected from the
      WATCH cohort.

PMID- 22374368
TI  - Multiple defender effects: synergistic coral defense by mutualist crustaceans.
AB  - The majority of our understanding of mutualisms comes from studies of pairwise
      interactions. However, many hosts support mutualist guilds, and interactions
      among mutualists make the prediction of aggregate effects difficult. Here, we
      apply a factorial experiment to interactions of 'guard' crustaceans that defend
      their coral host from seastar predators. Predation was reduced by the presence of
      mutualists (15% reduction in predation frequency and 45% in volume of coral
      consumed). The frequency of attacks with both mutualists was lower than with a
      single species, but it did not differ significantly from the expected frequency
      of independent effects. In contrast, the combined defensive efficacy of both
      mutualist species reduced the volume of coral tissue lost by 73%, significantly
      more than the 38% reduction expected from independent defensive efforts,
      suggesting the existence of a cooperative synergy in defensive behaviors of
      'guard' crustaceans. These emergent 'multiple defender effects' are statistically
      and ecologically analogous to the emergent concept of 'multiple predator effects'
      known from the predation literature.

PMID- 22374370
TI  - Counterspaces: a unit of analysis for understanding the role of settings in
      marginalized individuals' adaptive responses to oppression.
AB  - Research and theory on the intervening variables that enable individuals who
      experience marginalization and oppression to achieve well-being have historically
      relied on an individual level of analysis. Yet, there is a growing body of
      literature that highlights the roles that contexts play in facilitating processes
      that result in wellness among marginalized individuals. This paper proposes a
      conceptual framework that highlights a specific type of setting, referred to as
      "counterspaces," which promotes the psychological well-being of individuals who
      experience oppression. Counterspaces are theorized to enhance well-being by
      challenging deficit-oriented societal narratives concerning marginalized
      individuals' identities. The conceptual frame proposed here suggests that
      "challenging" can occur through at least three processes: (1) narrative identity
      work, (2) acts of resistance, and (3) direct relational transactions. This paper
      articulates each of these challenging processes. Additionally, the utility of
      using the Counterspaces framework for thinking critically about and investigating
      how settings-and the transactional processes that unfold within them-are
      associated with the promotion of psychological wellness for various marginalized
      populations is discussed.

PMID- 22374369
TI  - Carotid vasculature modeling from patient CT angiography studies for
      interventional procedures simulation.
AB  - OBJECTIVE: A practical method for patient-specific modeling of the aortic arch
      and the entire carotid vasculature from computed tomography angiography (CTA)
      scans for morphologic analysis and for interventional procedure simulation.
      MATERIALS AND METHODS: The method starts with the automatic watershed-based
      segmentation of the aorta and the construction of an a-priori intensity
      probability distribution function for arteries. The carotid arteries are then
      segmented with a graph min-cut method based on a new edge weighting function that
      adaptively couples voxel intensity, intensity prior, and local vesselness shape
      prior. Finally, the same graph-cut optimization framework is used to
      interactively remove a few unwanted veins segments and to fill in minor vessel
      discontinuities caused by intensity variations. RESULTS: We validate our modeling
      method with two experimental studies on 71 multicenter clinical CTA datasets,
      including carotid bifurcation lumen segmentation on 56 CTAs from the MICCAI'2009
      3D Segmentation Challenge. Segmentation results show that our method is
      comparable to the best existing methods and was successful in modeling the entire
      carotid vasculature with a Dice similarity measure of 84.5% (SD = 3.3%) and MSSD
      0.48 mm (SD = 0.12 mm.) Simulation study shows that patient-specific simulations
      with four patient-specific models generated by our segmentation method on the
      ANGIO MentorTM simulator platform are robust, realistic, and greatly improve the
      simulation. CONCLUSION: This constitutes a proof-of-concept that patient-specific
      CTA-based modeling and simulation of carotid interventional procedures are
      practical in a clinical environment.

PMID- 22374371
TI  - Low-power analog integrated circuits for wireless ECG acquisition systems.
AB  - This paper presents low-power analog ICs for wireless ECG acquisition systems.
      Considering the power-efficient communication in the body sensor network, the
      required low-power analog ICs are developed for a healthcare system through
      miniaturization and system integration. To acquire the ECG signal, a low-power
      analog front-end system, including an ECG signal acquisition board, an on-chip
      low-pass filter, and an on-chip successive-approximation analog-to-digital
      converter for portable ECG detection devices is presented. A quadrature CMOS
      voltage-controlled oscillator and a 2.4 GHz direct-conversion transmitter with a
      power amplifier and upconversion mixer are also developed to transmit the ECG
      signal through wireless communication. In the receiver, a 2.4 GHz fully
      integrated CMOS RF front end with a low-noise amplifier, differential power
      splitter, and quadrature mixer based on current-reused folded architecture is
      proposed. The circuits have been implemented to meet the specifications of the
      IEEE 802.15.4 2.4 GHz standard. The low-power ICs of the wireless ECG acquisition
      systems have been fabricated using a  0.18 MUm Taiwan Semiconductor Manufacturing
      Company (TSMC) CMOS standard process. The measured results on the human body
      reveal that ECG signals can be acquired effectively by the proposed low-power
      analog front-end ICs.

PMID- 22374372
TI  - Trigger learning and ECG parameter customization for remote cardiac clinical care
      information system.
AB  - Coronary heart disease is being identified as the largest single cause of death
      along the world. The aim of a cardiac clinical information system is to achieve
      the best possible diagnosis of cardiac arrhythmias by electronic data processing.
      Cardiac information system that is designed to offer remote monitoring of patient
      who needed continues follow up is demanding. However, intra- and interpatient
      electrocardiogram (ECG) morphological descriptors are varying through the time as
      well as the computational limits pose significant challenges for practical
      implementations. The former requires that the classification model be adjusted
      continuously, and the latter requires a reduction in the number and types of ECG
      features, and thus, the computational burden, necessary to classify different
      arrhythmias. We propose the use of adaptive learning to automatically train the
      classifier on up-to-date ECG data, and employ adaptive feature selection to
      define unique feature subsets pertinent to different types of arrhythmia.
      Experimental results show that this hybrid technique outperforms conventional
      approaches and is, therefore, a promising new intelligent diagnostic tool.

PMID- 22374373
TI  - Potential impact of accelerating the primary dose of rotavirus vaccine in
      infants.
AB  - We estimated the potential impact of administering the first dose of rotavirus
      vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is
      permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus
      hospitalization rates. We used published data for hospitalization rates, vaccine
      coverage, and vaccine efficacy after one dose and assumed a two-week delay in
      seroconversion after vaccine administration in the United States. Administering
      the first dose of rotavirus vaccine at 6 weeks instead of 8 weeks of age should
      have prevented 1110, 1660, and 2210 rotavirus hospitalizations among U.S. infants
      <3 months of age in 2006 when the vaccine was first introduced. This estimated
      benefit represents a 2-4% reduction in rotavirus hospitalizations among children
      <5 years of age.

PMID- 22374374
TI  - Acceptance of vaccination during pregnancy: experience with 2009 influenza A
      (H1N1) in the Netherlands.
AB  - OBJECTIVES: In 2009, the Dutch government advised pregnant women to get
      vaccinated against influenza A (H1N1). A study was set up to gain insight into
      vaccination coverage and reasons why pregnant women seek vaccination or not.
      METHODS: We invited 14,529 pregnant women to complete an internet survey on
      vaccination during pregnancy in general and against 2009 influenza A (H1N1).
      Differences in background characteristics between unvaccinated and vaccinated
      women were investigated. Prediction analyses were carried out to determine which
      survey statement had the greatest impact on vaccination status or intention to
      get vaccinated during pregnancy. RESULTS: Of the 2993 included respondents, 63%
      reported to be vaccinated against 2009 influenza A (H1N1). Vaccination coverage
      was higher among older birth cohorts, women who had been pregnant before, women
      with underlying medical conditions, and women who reported no defined 'life
      philosophy'. Protection of the child (after birth), the government's advice and
      possible harmful effects of the vaccine for the unborn child had the greatest
      predictive value for vaccination status. With regards vaccination during future
      pregnancies, 39% had a positive intention to obtain vaccination and 45% were
      neutral. The government's advice was the strongest predictor for intention.
      Furthermore, women expressed concern over lack of sufficient knowledge about
      vaccine safety. CONCLUSIONS: A considerable number of pregnant women in the
      Netherlands reported to be vaccinated against 2009 influenza A (H1N1). The
      challenge for the government in the future will be to provide pregnant women and
      health care professionals with sufficient and clear information about disease
      severity and the benefits and safety of vaccination.

PMID- 22374375
TI  - Three-dimensional microfiber devices that mimic physiological environments to
      probe cell mechanics and signaling.
AB  - Many physiological systems are regulated by cells that alter their behavior in
      response to changes in their biochemical and mechanical environment. These cells
      experience this dynamic environment through an endogenous biomaterial matrix that
      transmits mechanical force and permits chemical exchange with the surrounding
      tissue. As a result, in vitro systems that mimic three-dimensional, in vivo
      cellular environments can enable experiments that reveal the nuanced interplay
      between biomechanics and physiology. Here we report the development of a minimal
      profile, three-dimensional (MP3D) experimental microdevice that confines cells to
      a single focal plane, while allowing the precise application of mechanical
      displacement to cells and concomitant access to the cell membrane for perfusion
      with biochemical agonists. The MP3D device--an ordered microfiber scaffold
      erected on glass--provides a cellular environment that induces physiological cell
      morphologies. Small manipulations of the scaffold's microfibers allow attached
      cells to be mechanically probed. Due to the scaffold's minimal height profile,
      MP3D devices confine cells to a single focal plane, facilitating observation with
      conventional epifluorescent microscopy. When examining fibroblasts within MP3D
      devices, we observed robust cellular calcium responses to both a chemical
      stimulus as well as mechanical displacement of the cell membrane. The observed
      response differed significantly from previously reported, mechanically-induced
      calcium responses in the same cell type. Our findings demonstrate a key link
      between environment, cell morphology, mechanics, and intracellular signal
      transduction. We anticipate that this device will broadly impact research in
      fields including biomaterials, tissue engineering, and biophysics.

PMID- 22374376
TI  - Concepts of metastasis in flux: the stromal progression model.
AB  - The ability of tumor cells to leave a primary tumor, to disseminate through the
      body, and to ultimately seed new secondary tumors is universally agreed to be the
      basis for metastasis formation. An accurate description of the cellular and
      molecular mechanisms that underlie this multistep process would greatly
      facilitate the rational development of therapies that effectively allow
      metastatic disease to be controlled and treated. A number of disparate and
      sometimes conflicting hypotheses and models have been suggested to explain
      various aspects of the process, and no single concept explains the mechanism of
      metastasis in its entirety or encompasses all observations and experimental
      findings. The exciting progress made in metastasis research in recent years has
      refined existing ideas, as well as giving rise to new ones. In this review we
      survey some of the main theories that currently exist in the field, and show that
      significant convergence is emerging, allowing a synthesis of several models to
      give a more comprehensive overview of the process of metastasis. As a result we
      postulate a stromal progression model of metastasis. In this model, progressive
      modification of the tumor microenvironment is equally as important as genetic and
      epigenetic changes in tumor cells during primary tumor progression. Mutual
      regulatory interactions between stroma and tumor cells modify the stemness of the
      cells that drive tumor growth, in a manner that involves epithelial-mesenchymal
      and mesenchymal-epithelial-like transitions. Similar interactions need to be
      recapitulated at secondary sites for metastases to grow. Early disseminating
      tumor cells can progress at the secondary site in parallel to the primary tumor,
      both in terms of genetic changes, as well as progressive development of a
      metastatic stroma. Although this model brings together many ideas in the field,
      there remain nevertheless a number of major open questions, underscoring the need
      for further research to fully understand metastasis, and thereby identify new and
      effective ways of treating metastatic disease.

PMID- 22374377
TI  - A study of low-dose S-ketamine infusion as "preventive" pain treatment for
      cesarean section with spinal anesthesia: benefits and side effects.
AB  - BACKGROUND: Attenuation of central sensitization with NMDA-active drugs such as S
      Ketamine may play a role in postoperative analgesia and prevention of neuropathic
      pain. However, during cesarean section with neuraxial block, S-Ketamine might
      have adverse effects on the interaction between mothers and infants, including
      breastfeeding. METHODS: Women undergoing elective repeat cesarean section with
      subarachnoid anesthesia (0.5% hyperbaric bupivacaine 8-10 mg and sufentanil 5
      MUg) were enrolled in a double-blind, randomized study. Patients in the S
      Ketamine group (N.=28) received i.v. midazolam 0.02 mg/kg and S-Ketamine 0.5
      mg/kg i.m. bolus 10 minutes after birth followed by a 2 MUg/kg/min i.v.
      continuous infusion for 12 h. The control group (N.=28) received placebo.
      Paracetamol and patient controlled analgesia with intravenous morphine were given
      postoperatively. Von Frey filaments were used to assess pain threshold on the
      inner forearm and T10-T11 dermatomes (supposed hyperalgesic area). RESULTS: S
      Ketamine reduced morphine consumption at 4-8, 8-12, and 12-24 hours after surgery
      (total 31%), even after its effect has ceased, suggesting an anti-hyperalgesic
      action. Mild side effects were observed in the S-Ketamine group one hour after
      delivery. All side effects were rated as light and there were no serious adverse
      events. Pain threshold was not significantly different between groups. S-Ketamine
      patients showed a trend towards reduced pain sensitivity at the T10 dermatome,
      which is involved by surgical damage. After three years, patients reported no
      differences in residual pain, dysesthetic symptoms, or duration of breast
      feeding. CONCLUSION: Preventive administration of S-Ketamine via 12-hour infusion
      was safe and may have anti-hyperalgesic action after cesarean section.

PMID- 22374378
TI  - Neuromuscular block in Italy: a survey of current management.
AB  - BACKGROUND: Little is known about current use of neuromuscular blocking agents by
      Italian anesthetists. This paper reports the results of a survey conducted to
      obtain information about current management of neuromuscular block in Italy.
      METHODS: A questionnaire was given to Italian Anesthetists attending the 64nd
      National Congress of the Italian Society of Anesthesia, Intensive Care, Analgesia
      and Intensive Therapy S.I.A.A.R.T.I. (Parma, 13th-16th October 2010). Collected
      data were stratified by age, geographical location, and the total number of
      surgical procedures performed in the hospitals concerned. RESULTS: One thousand
      four hundred forty patients correctly compiled questionnaires were collected. 50%
      of respondents used clinical tests to monitor the level of neuromuscular
      blockade. The main clinical tests cited for the evaluation were: keeping the head
      lifted up for 5 seconds, protruding the tongue and opening the eyes. Train-of
      four was used by 50% of respondents on a routine basis. Only 33% of anesthetists
      reply that a train-of-four ratio of 90% or more is the safe level prior to
      extubation. CONCLUSION: Clinical signs are used by most of the Italian
      anesthetists to assess the recovery from neuromuscular blockade. There is poor
      awareness about their inability to indicate even a significant degree of residual
      neuromuscular block. A more extensive use of quantitative instrumental monitoring
      is required for the more rational use of neuromuscular blocking agents.

PMID- 22374379
TI  - Increase in N-terminus-pro-B-type natriuretic peptide during exercise of patients
      with univentricular heart after a total cavopulmonary connection.
AB  - An increase in N-terminus pro-B-type natriuretic peptide (NT-proBNP) during
      exercise is related to myocardial ischemia, myocardial dysfunction, and
      inflammatory stress. Its value for patients with a univentricular heart after
      total cavopulmonary connection (TCPC) is unknown. For 66 patients with TCPC, a
      cardiopulmonary exercise test was performed. Venous NT-proBNP samples were drawn
      with the patient at rest and then 2-3 min after peak exercise. The median NT
      proBNP during rest was 82 ng/l (range, 11-2,554 ng/l), with 22 patients above the
      upper reference limit. A higher NT-proBNP during rest was related to a worse peak
      oxygen uptake (peak [Formula: see text]), a higher ventilatory equivalent
      (VE/VCO(2) slope), and a need for diuretics administration. A small but
      significant increase in NT-proBNP during exercise at 6 ng/l (range, 0-314 ng/l)
      was related mainly to its resting value. The relative increase was solely related
      to a higher body mass and not to any of the investigated functional parameters.
      Usually, NT-proBNP during rest is not elevated in TCPC patients. If so, it is a
      valuable predictor of cardiac function. During exercise, only a minor increase in
      NT-proBNP occurs. Its extent is not related to any of the investigated functional
      parameters. Maybe the filling restriction from the lungs prevents atrial and
      ventricular overload as well as BNP secretion in TCPC patients.

PMID- 22374380
TI  - Hypertrophic cardiomyopathy with cardiac rupture and tamponade caused by
      congenital disorder of glycosylation type Ia.
AB  - Hypertrophic cardiomyopathy (HCM) is a rare presenting feature of congenital
      disorder of glycosylation type Ia (CDG-Ia). We report two female siblings with
      CDG-Ia and cardiomyopathy. Patient no. 1 died at 12 days of age from cardiac
      rupture and tamponade, which has not previously been reported in CDG-Ia. The
      second patient died at 2 months of age from HCM. The severe cardiac
      manifestations seen in our patients emphasize the importance of early cardiac
      assessment in all patients with CDG-Ia.

PMID- 22374383
TI  - Cutaneous microdialysis: cytokine evidence for altered innate reactivity in the
      skin of psoriasis patients?
AB  - Cutaneous microdialysis demonstrates cytokine production in living human skin. In
      the present study, microdialysis samples taken from uninvolved and lesional skin
      in three test subjects with psoriasis over 24 h have been investigated for
      cytokine content with a bead-based multiplex immunoassay from Luminex.
      Concentration curves for a set of Th1/Th2 and pro-inflammatory cytokines measured
      differed from a reference group of ten subjects without psoriasis. The time to
      return to near baseline values after innate insertion reactivity is between 9 and
      16 h. Post-equilibration levels (17-24 h) for the three main cytokines elevated
      in the reference group were differentially elevated outside the range of the
      reference group for interleukin-1beta (IL1beta) and IL8 but not so for IL6. Two
      further cytokines, granulocyte-macrophage colony-stimulating factor and tumor
      necrosis factor-alpha not generally elevated in the reference group, showed
      elevated values in the test subjects. Multivariate time series analysis
      (chemometry) showed that cytokine patterns for the individual test subjects often
      fell outside the 99% confidence intervals of a model generated from the reference
      group. In a clinical research situation, cutaneous microdialysis is feasible,
      gives generally higher cytokine levels than in the blood and generates
      interpretable data on an individual's reactivity compared with a reference group.
      This may well prove useful in delineation of pathogenetic issues, selection of
      appropriate therapy and monitoring of subsequent response in inflammatory
      dermatoses such as psoriasis.

PMID- 22374384
TI  - An investigation into the utility of a multi-compartmental, dynamic, system of
      the upper gastrointestinal tract to support formulation development and establish
      bioequivalence of poorly soluble drugs.
AB  - In recent years mechanical systems have been developed that more closely mimic
      the full dynamic, physical and biochemical complexity of the GI Tract. The
      development of these complex systems raises the possibility that they could be
      used to support formulation development of poorly soluble compounds and
      importantly may be able to replace clinical BE studies in certain circumstances.
      The ability of the TNO Simulated Gastro-Intestinal Tract Model 1 (TIM-1) Dynamic
      Artificial Gastrointestinal System in the 'lipid membrane' configuration to
      support the development of Biopharmaceutics Classification System Class 2
      compounds was investigated by assessing the performance of various AZD8055 drug
      forms and formulations in the TIM-1 system under standard fasting and
      achlorhydric physiological conditions. The performance data were compared with
      exposure data from the phase 1 clinical study. Analysis of the AZD8055 plasma
      concentrations after tablet administration supported the conclusions drawn from
      the TIM-1 experiments and confirmed that these complex systems can effectively
      support the product development of poorly soluble drugs. Particularly, the TIM-1
      system was able to show that AZD8055 exposure would increase in an approximately
      dose proportional manner and not be limited by the solubility or dissolution.
      Additionally, the investigations also showed that the exposure produced by a
      solution and a tablet would be the same. Specific instances when the TIM-1 system
      may not be predictive of clinical product performance have also been identified.

PMID- 22374385
TI  - Late complications after pancreaticoduodenectomy with pancreaticogastrostomy.
AB  - INTRODUCTION: We investigated complications after pancreaticoduodenectomy (PD)
      with pancreaticogastrostomy (PG) reconstruction more than 12 months
      postoperatively. METHODS: Through chart review and outpatient follow-up, we
      assessed the incidence of new-onset diabetes mellitus (DM) and steatorrhea after
      PD. RESULTS: Ninety patients underwent PD with PG with a median follow-up of 4.7
      years (range 0.4-15.8 years). Of the 77 patients without DM preoperatively, 18
      (23.4%) developed DM postoperatively. Those who developed DM were younger at time
      of surgery than those who did not (60.5 versus 65.8 years; p = 0.021), but
      postoperative survival did not differ between these groups. The incidence of DM
      was comparable to the incidence of DM in the general population. Out of 89
      patients, 47 (52.8%) now require pancreatic enzyme therapy. The group that
      developed steatorrhea underwent PD at a younger age (61.4 versus 67.0 years; p =
      0.029). CONCLUSIONS: Patients that undergo PD at a younger age are more likely to
      develop DM and steatorrhea than their older counterparts; patients are as likely
      as the general population, however, to develop DM after PD with PG.

PMID- 22374386
TI  - GrameneMart: the BioMart data portal for the Gramene project.
AB  - Gramene is a well-established resource for plant comparative genome analysis.
      Data are generated through automated and curated analyses and made available
      through web interfaces such as GrameneMart. The Gramene project was an early
      adopter of the BioMart software, which remains an integral and well-used
      component of the Gramene website. BioMart accessible data sets include plant gene
      annotations, plant variation catalogues, genetic markers, physical mapping
      entities, public DNA/mRNA sequences of various types and curated quantitative
      trait loci for various species. DATABASE URL:
      http://www.gramene.org/biomart/martview.

PMID- 22374387
TI  - Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular
      cells from brown adipose tissue, but fails to affect thermogenic function of
      brown adipocytes.
AB  - The thermogenic function of brown adipose tissue (BAT) is increased by
      norepinephrine (NE) released from sympathetic nerve endings, but the roles of NPY
      released along with NE are poorly elucidated. Here, we examined effect of NPY on
      basal and NE-enhanced thermogenesis in isolated brown adipocytes that express Y1
      and Y5 receptor mRNA. Treatment of cells with NPY did not influence the basal and
      NE-enhanced rates of oxygen consumption and cAMP accumulation. Treatment with NPY
      also failed to induce ERK (Thr202/Tyr204) phosphorylation in the brown
      adipocytes. In contrast, treatment with NPY increased ERK phosphorylation in
      cultured stromal vascular cells from the BAT that express Y1 receptor mRNA. In
      the latter treatment with NPY also increased STAT3 (Ser727) phosphorylation.
      These results suggest that NPY mainly acts on stromal vascular cells in BAT and
      plays roles in the regulation of their gene transcription through ERK and STAT3
      pathways, while NPY does not affect the thermogenic function of brown adipocytes.

PMID- 22374388
TI  - Polyphenylenepyridyl dendrimers as stabilizing and controlling agents for CdS
      nanoparticle formation.
AB  - Semiconductor nanoparticles (NPs) are being actively explored for applications in
      medical diagnostics and therapy and numerous electronic devices including solar
      cells. In this paper we demonstrate the influence of the third generation rigid
      polyphenylenepyridyl dendrimers (PPPDs) of a different architecture on the
      formation of well-defined CdS NPs. A high temperature approach to the synthesis
      of novel CdS/PPPD nanocomposites is feasible due to the high thermal stability of
      PPPDs. The PPPD architecture affects the CdS NP formation: larger NPs are
      obtained in the presence of dendrimers with 1,3,5-triphenylbenzene cores compared
      to those with tetrakis(4-ethynylphen-1-yl)methane cores. The reaction conditions
      such as concentrations of PPPDs and NP precursors and the temperature regime also
      influence the CdS NP sizes. For the first time, we elucidated a mechanism of CdS
      NP formation in a non-coordinating solvent through the CdO redispersion in the
      presence of PPPDs. Interesting optical properties of these CdS/PPPD
      nanocomposites make them promising candidates for imaging applications.

PMID- 22374389
TI  - Incidence of spinal haematoma after epidural puncture:  analysis from the German
      network for safety in regional anaesthesia.
AB  - CONTEXT: The incidence of epidural haematoma after epidural anaesthesia is
      uncertain. OBJECTIVE: To quantify epidural haematoma after epidural anaesthesia
      in 2008 and 2009 in a network for safety in regional anaesthesia in Germany.
      DESIGN: Analysis of data systematically documented within the German network for
      safety in regional anaesthesia. SETTING: A regional anaesthesia register for
      clinics recording their clinical practice was set up according to a consented
      protocol. After checking the registry for the presence of epidural haematoma, all
      participating centres were asked for the number of epidural haematoma and the
      number of neuraxial procedures performed during the 2 years. Patient-specific
      information regarding procedures and outcome were requested. MAIN OUTCOME
      MEASURES: The incidence of epidural haematoma in the network with comorbidities,
      coagulation status and time from first symptoms, also the performance of MRI and
      laminectomy. RESULTS: During a period of 2 years, 33,142 non-obstetric epidural
      blocks were performed. Five thoracic epidural and one cranial haematoma occurred.
      DISCUSSION: The incidence of spinal haematoma was 1: 6 628 in this general
      surgical population. When local anaesthetics are continuously applied,
      progressive motor block should increase the level of suspicion. When accompanied
      by pain or paraesthesia, progression to diagnosis by MRI is mandatory.

PMID- 22374390
TI  - A survey of anaesthetic practice in predicting difficult intubation in UK and
      Europe.
AB  - CONTEXT: Unexpected difficulty in tracheal intubation is an intermittent and
      often terrifying problem for all practising anaesthetists. There are many
      preoperative assessment tests to predict a difficult laryngeal view or a
      difficult intubation, but we found no published evidence of how frequently these
      predictive tests are used or how useful they are perceived to be by
      anaesthetists. OBJECTIVE: We decided to ask UK and non-UK anaesthetists attending
      the Annual Scientific Meeting of the European Society of Anaesthesiology about
      their practice in predicting difficult intubation. DESIGN: The study was
      conceived as a survey. SETTING: The airway tests were compiled into a
      questionnaire, hand distributed among anaesthetists at Euroanaesthesia - the
      European group (after excluding UK attendees) - and posted to randomly selected
      anaesthetists in the UK - the UK group. PARTICIPANTS: Overall, 888 of 1230 (72%)
      questionnaires were completed. The response rate from the UK group of
      anaesthetists was 69% (481 of 700) and from the European group was 77% (407 of
      530). RESULTS: On a scale 1 (never) to 5 (always), the mean score for frequency
      of use was similar for both groups of anaesthetists and ranged from about 4 for
      mouth opening to about 1 for Nodding Donkey. The mean score for usefulness (1 =
      useless, 5 = extremely useful) ranged from about 3.7 to 2 for the same two tests.
      The UK group found most tests slightly less useful than did the European group.
      With regard to the frequency of assessing the airway, 9% of the European group,
      but 16% of the UK group, failed always (score 5) or regularly (score 4) to assess
      the airway before general anaesthesia. Furthermore, 21 and 36% of the UK and
      European groups, respectively, failed to do so before regional anaesthesia.
      CONCLUSION: These results are a cause for concern with regard to both airway
      management training and patient safety.

PMID- 22374391
TI  - Nicotianamine in zinc and iron homeostasis.

PMID- 22374392
TI  - Nuclear phytochrome A signaling promotes phototropism in Arabidopsis.
AB  - Phototropin photoreceptors (phot1 and phot2 in Arabidopsis thaliana) enable
      responses to directional light cues (e.g., positive phototropism in the
      hypocotyl). In Arabidopsis, phot1 is essential for phototropism in response to
      low light, a response that is also modulated by phytochrome A (phyA),
      representing a classical example of photoreceptor coaction. The molecular
      mechanisms underlying promotion of phototropism by phyA remain unclear. Most phyA
      responses require nuclear accumulation of the photoreceptor, but interestingly,
      it has been proposed that cytosolic phyA promotes phototropism. By comparing the
      kinetics of phototropism in seedlings with different subcellular localizations of
      phyA, we show that nuclear phyA accelerates the phototropic response, whereas in
      the fhy1 fhl mutant, in which phyA remains in the cytosol, phototropic bending is
      slower than in the wild type. Consistent with this data, we find that
      transcription factors needed for full phyA responses are needed for normal
      phototropism. Moreover, we show that phyA is the primary photoreceptor promoting
      the expression of phototropism regulators in low light (e.g., PHYTOCHROME KINASE
      SUBSTRATE1 [PKS1] and ROOT PHOTO TROPISM2 [RPT2]). Although phyA remains
      cytosolic in fhy1 fhl, induction of PKS1 and RPT2 expression still occurs in fhy1
      fhl, indicating that a low level of nuclear phyA signaling is still present in
      fhy1 fhl.

PMID- 22374393
TI  - Roles of the middle domain-specific WUSCHEL-RELATED HOMEOBOX genes in early
      development of leaves in Arabidopsis.
AB  - During leaf development in flowering plants, adaxial (upper) and abaxial (lower)
      side-specific genes are responsible for blade outgrowth, which takes places
      predominantly in the lateral direction, and for margin development as well as
      differentiation of adaxial and abaxial tissues. However, the underlying
      mechanisms are poorly understood. Here, we show that two WUSCHEL-RELATED HOMEOBOX
      (WOX) genes, PRESSED FLOWER (PRS)/WOX3 and WOX1, encoding homeobox transcription
      factors, act in blade outgrowth and margin development downstream of
      adaxial/abaxial polarity establishment. The expression of PRS and WOX1 defines a
      hitherto undescribed middle domain, including two middle mesophyll layers and the
      margin, as a center that organizes the outgrowth of leaf blades. The expression
      of PRS and WOX1 is repressed in the abaxial leaf domain by the abaxial-specific
      transcription factor KANADI. Furthermore, PRS and WOX1 coordinate adaxial/abaxial
      patterning together with adaxial- and abaxial-specific genes. Our data suggest a
      model of blade outgrowth and adaxial/abaxial patterning via the middle domain
      specific WOX genes in Arabidopsis thaliana leaves.

PMID- 22374395
TI  - Elevated nicotianamine levels in Arabidopsis halleri roots play a key role in
      zinc hyperaccumulation.
AB  - Zn deficiency is among the leading health risk factors in developing countries.
      Breeding of Zn-enriched crops is expected to be facilitated by molecular
      dissection of plant Zn hyperaccumulation (i.e., the ability of certain plants to
      accumulate Zn to levels >100-fold higher than normal plants). The model
      hyperaccumulators Arabidopsis halleri and Noccaea caerulescens share elevated
      nicotianamine synthase (NAS) expression relative to nonaccumulators among a core
      of alterations in metal homeostasis. Suppression of Ah-NAS2 by RNA interference
      (RNAi) resulted in strongly reduced root nicotianamine (NA) accumulation and a
      concomitant decrease in root-to-shoot translocation of Zn. Speciation analysis by
      size-exclusion chromatography coupled to inductively coupled plasma mass
      spectrometry showed that the dominating Zn ligands in roots were NA and thiols.
      In NAS2-RNAi plants, a marked increase in Zn-thiol species was observed. Wild
      type A. halleri plants cultivated on their native soil showed elemental profiles
      very similar to those found in field samples. Leaf Zn concentrations in NAS2-RNAi
      lines, however, did not reach the Zn hyperaccumulation threshold. Leaf Cd
      accumulation was also significantly reduced. These results demonstrate a role for
      NAS2 in Zn hyperaccumulation also under near-natural conditions. We propose that
      NA forms complexes with Zn(II) in root cells and facilitates symplastic passage
      of Zn(II) toward the xylem.

PMID- 22374394
TI  - Vitamin deficiencies in humans: can plant science help?
AB  - The term vitamin describes a small group of organic compounds that are absolutely
      required in the human diet. Although for the most part, dependency criteria are
      met in developed countries through balanced diets, this is not the case for the
      five billion people in developing countries who depend predominantly on a single
      staple crop for survival. Thus, providing a more balanced vitamin intake from
      high-quality food remains one of the grandest challenges for global human
      nutrition in the coming decade(s). Here, we describe the known importance of
      vitamins in human health and current knowledge on their metabolism in plants.
      Deficits in developing countries are a combined consequence of a paucity of
      specific vitamins in major food staple crops, losses during crop processing,
      and/or overreliance on a single species as a primary food source. We discuss the
      role that plant science can play in addressing this problem and review successful
      engineering of vitamin pathways. We conclude that while considerable advances
      have been made in understanding vitamin metabolic pathways in plants, more cross
      disciplinary approaches must be adopted to provide adequate levels of all
      vitamins in the major staple crops to eradicate vitamin deficiencies from the
      global population.

PMID- 22374396
TI  - Transcriptome sequencing identifies SPL7-regulated copper acquisition genes
      FRO4/FRO5 and the copper dependence of iron homeostasis in Arabidopsis.
AB  - The transition metal copper (Cu) is essential for all living organisms but is
      toxic when present in excess. To identify Cu deficiency responses
      comprehensively, we conducted genome-wide sequencing-based transcript profiling
      of Arabidopsis thaliana wild-type plants and of a mutant defective in the gene
      encoding SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7), which acts as a
      transcriptional regulator of Cu deficiency responses. In response to Cu
      deficiency, FERRIC REDUCTASE OXIDASE5 (FRO5) and FRO4 transcript levels increased
      strongly, in an SPL7-dependent manner. Biochemical assays and confocal imaging of
      a Cu-specific fluorophore showed that high-affinity root Cu uptake requires prior
      FRO5/FRO4-dependent Cu(II)-specific reduction to Cu(I) and SPL7 function. Plant
      iron (Fe) deficiency markers were activated in Cu-deficient media, in which
      reduced growth of the spl7 mutant was partially rescued by Fe supplementation.
      Cultivation in Cu-deficient media caused a defect in root-to-shoot Fe
      translocation, which was exacerbated in spl7 and associated with a lack of
      ferroxidase activity. This is consistent with a possible role for a multicopper
      oxidase in Arabidopsis Fe homeostasis, as previously described in yeast, humans,
      and green algae. These insights into root Cu uptake and the interaction between
      Cu and Fe homeostasis will advance plant nutrition, crop breeding, and
      biogeochemical research.

PMID- 22374397
TI  - Vacuolar nicotianamine has critical and distinct roles under iron deficiency and
      for zinc sequestration in Arabidopsis.
AB  - The essential micronutrients Fe and Zn often limit plant growth but are toxic in
      excess. Arabidopsis thaliana ZINC-INDUCED FACILITATOR1 (ZIF1) is a vacuolar
      membrane major facilitator superfamily protein required for basal Zn tolerance.
      Here, we show that overexpression of ZIF1 enhances the partitioning into vacuoles
      of the low molecular mass metal chelator nicotianamine and leads to pronounced
      nicotianamine accumulation in roots, accompanied by vacuolar buildup of Zn.
      Heterologous ZIF1 protein localizes to vacuolar membranes and enhances
      nicotianamine contents of yeast cells engineered to synthesize nicotianamine,
      without complementing a Zn-hypersensitive mutant that additionally lacks vacuolar
      membrane Zn(2+)/H(+) antiport activity. Retention in roots of Zn, but not of Fe,
      is enhanced in ZIF1 overexpressors at the expense of the shoots. Furthermore,
      these lines exhibit impaired intercellular Fe movement in leaves and constitutive
      Fe deficiency symptoms, thus phenocopying nicotianamine biosynthesis mutants.
      Hence, perturbing the subcellular distribution of the chelator nicotianamine has
      profound, yet distinct, effects on Zn and Fe with respect to their subcellular
      and interorgan partitioning. The zif1 mutant is also hypersensitive to Fe
      deficiency, even in media lacking added Zn. Therefore, accurate levels of ZIF1
      expression are critical for both Zn and Fe homeostasis. This will help to advance
      the biofortification of crops.

PMID- 22374399
TI  - The signal transducer NPH3 integrates the phototropin1 photosensor with PIN2
      based polar auxin transport in Arabidopsis root phototropism.
AB  - Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the
      light source, showing a negative phototropic response. However, the mechanism of
      root phototropism is still unclear. Using a noninvasive microelectrode system, we
      showed that the BL sensor phototropin1 (phot1), the signal transducer
      NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were
      essential for BL-induced auxin flux in the root apex transition zone. We also
      found that PIN2-green fluorescent protein (GFP) localized to vacuole-like
      compartments (VLCs) in dark-grown root epidermal and cortical cells, and
      phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the
      plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2
      GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs
      and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the
      nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP
      from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both
      dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles
      in PIN2 localization. In conclusion, BL-induced root phototropism is based on the
      phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by
      modifying the subcellular targeting of PIN2 in the root apex transition zone.

PMID- 22374398
TI  - The conjugated auxin indole-3-acetic acid-aspartic acid promotes plant disease
      development.
AB  - Auxin is a pivotal plant hormone that regulates many aspects of plant growth and
      development. Auxin signaling is also known to promote plant disease caused by
      plant pathogens. However, the mechanism by which this hormone confers
      susceptibility to pathogens is not well understood. Here, we present evidence
      that fungal and bacterial plant pathogens hijack the host auxin metabolism in
      Arabidopsis thaliana, leading to the accumulation of a conjugated form of the
      hormone, indole-3-acetic acid (IAA)-Asp, to promote disease development. We also
      show that IAA-Asp increases pathogen progression in the plant by regulating the
      transcription of virulence genes. These data highlight a novel mechanism to
      promote plant susceptibility to pathogens through auxin conjugation.

PMID- 22374400
TI  - Solitary pulmonary nodules differentiated by dynamic F-18 FDG PET in a region
      with high prevalence of granulomatous disease.
AB  - This study determined whether dynamic F-18 FDG PET imaging could differentiate
      benign from malignant solitary pulmonary nodules (SPNs). Histopathologically
      confirmed SPNs (10-35 mm), 24 malignant and 10 benign, from 34 patients were
      studied through both dynamic and static F-18 FDG PET imaging of all patients.
      Volumes of interest (VOIs) were placed over the pulmonary nodules using a 50%
      maximum pixel value threshold. The arterial input function was estimated from a
      left ventricle-defined VOI. Based on Patlak analysis, we calculated the net FDG
      phosphorylation rate (K(i)) and glucose metabolic rate (MRGlu) of each nodule.
      The slope values of the time-activity curves (TACs) of the nodules were also
      determined. Based on the static PET images, maximum and mean standardized uptake
      values (SUV(max) and SUV(mean), respectively) were calculated. Benign and
      malignant SPNs had significantly different values for SUV(max), SUV(mean), K(i),
      MRGlu, and TAC slope, with area under the receiver operating characteristic
      curves distinguishing benign from malignant nodules. McNemar's test of marginal
      homogeneity found all the predictors helpful to detect malignant nodules (all, p
      > 0.05), and combining K(i) and MRGlu, which were generated by dynamic study,
      yielded a higher specificity of 90%, and a sensitivity of 79%. Among the 10
      benign nodules, static SUV imaging correctly classified seven, while dynamic F-18
      PET imaging correctly classified nine. Dynamic F-18 FDG PET imaging is valuable
      in differentiating benign from malignant SPNs, particularly for granulomatous
      disease.

PMID- 22374401
TI  - Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for
      patients after extrapleural pneumonectomy for malignant pleural mesothelioma.
AB  - Postoperative hemithoracic irradiation is regarded as an important part of the
      curative treatment for resectable malignant pleural mesothelioma (MPM). Because
      the clinical target volume in postoperative MPM is irregular and surrounded by
      dose-limiting critical structures, intensity-modulated radiation therapy (IMRT)
      is thought to be suitable. However, postoperative hemithoracic IMRT remains
      experimental due to a high incidence of fatal pneumonitis. Therefore, a Phase I
      dose escalation study for hemithoracic IMRT using helical tomotherapy was
      planned, and the results of the first three patients are herein reported because
      this technique may provide benefits to such patients. For 3 patients with
      postoperative MPM, who were treated by extrapleural pneumonectomy (EPP), a
      radiation dose of 45.0 Gy in 25 fractions was given to cover 95% of the PTV. The
      lung V5s of the three patients were 14.3%, 10.0%, and 31.3%, respectively. The
      V5s of the present plans was smaller than that of the recent IMRT planning
      studies. The lung V20s of these patients were 2.4%, 2.2%, and 4.3%, respectively.
      Their MLDs were 4.3 Gy, 3.4 Gy, and 5.8 Gy, respectively. The follow-up periods
      of the patients were 26, 14 and 9 months from initiation of IMRT, respectively.
      All patients were alive, although local and contralateral recurrences had
      developed in 1 patient. Only 1 patient had Grade 2 acute esophagitis and nausea.
      There was no treatment-related pneumonitis. Hemithoracic IMRT using helical
      tomotherapy may play a crucial role in adjuvant treatment for MPM after EPP.

PMID- 22374402
TI  - Expression of p53-regulated proteins in human cultured lymphoblastoid TSCE5 and
      WTK1 cell lines during spaceflight.
AB  - The aim of this study was to determine the biological effects of space
      radiations, microgravity, and the interaction of them on the expression of p53
      regulated proteins. Space experiments were performed with two human cultured
      lymphoblastoid cell lines: one line (TSCE5) bears a wild-type p53 gene status,
      and another line (WTK1) bears a mutated p53 gene status. Under 1 gravity or
      microgravity conditions, the cells were grown in the cell biology experimental
      facility (CBEF) of the International Space Station for 8 days without
      experiencing the stress during launching and landing because the cells were
      frozen during these periods. Ground control samples were simultaneously cultured
      for 8 days in the CBEF on the ground for 8 days. After spaceflight, protein
      expression was analyzed using a Panorama(TM) Ab MicroArray protein chips. It was
      found that p53-dependent up-regulated proteins in response to space radiations
      and space environment were MeCP2 (methyl CpG binding protein 2), and Notch1
      (Notch homolog 1), respectively. On the other hand, p53-dependent down-regulated
      proteins were TGF-beta, TWEAKR (tumor necrosis factor-like weak inducer of
      apoptosis receptor), phosho-Pyk2 (Proline-rich tyrosine kinase 2), and 14-3
      3theta/tau which were affected by microgravity, and DR4 (death receptor 4), PRMT1
      (protein arginine methyltransferase 1) and ROCK-2 (Rho-associated, coiled-coil
      containing protein kinase 2) in response to space radiations. ROCK-2 was also
      suppressed in response to the space environment. The data provides the p53
      dependent regulated proteins by exposure to space radiations and/or microgravity
      during spaceflight. Our expression data revealed proteins that might help to
      advance the basic space radiation biology.

PMID- 22374403
TI  - Low-dose radiation induces Drosophila innate immunity through Toll pathway
      activation.
AB  - Numerous studies report that exposing certain organisms to low-dose radiation
      induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing
      survival after bacterial infection and antimicrobial peptide gene expression in
      irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances
      innate immunity. Low-dose irradiation of flies significantly increased resistance
      against gram-positive and gram-negative bacterial infections, as well as
      expression of several antimicrobial peptide genes. Additionally, low-dose
      irradiation also resulted in a specific increase in expression of key proteins of
      the Toll signaling pathway and phosphorylated forms of p38 and JNK. These results
      indicate that innate immunity is activated after low-dose irradiation through
      Toll signaling pathway in Drosophila.

PMID- 22374404
TI  - Screening high-grade vesicoureteral reflux in young infants with a febrile
      urinary tract infection.
AB  - BACKGROUND: The lack of good evidence for improved outcomes in children and young
      infants with febrile urinary tract infection (UTI) after aggressive treatment for
      vesicoureteral reflux (VUR) has raised doubts regarding the need for routine
      voiding cystourethrography (VCUG), and the appropriate imaging evaluation in
      these children remains controversial. OBJECTIVES: This prospective study aimed to
      determine whether abnormalities found on acute dimercaptosuccinic acid (DMSA)
      scan and ultrasound (US) can help indicate the necessity of voiding
      cystourethrography (VCUG) in young infants. METHODS: For 3.5 years, all infants
      younger than 3 months presenting with first febrile UTI were prospectively
      studied. All infants were hospitalized and investigated using US (<3 days after
      admission), DMSA scan (<5 days after admission), and VCUG (7-10 days after
      antibiotic treatment) after diagnosis. The association among findings of US, DMSA
      scan, and VCUG were evaluated. RESULTS: From 220 infants, there were abnormal
      results in 136 (61.8%) US and in 111 (50.5%) DMSA scans. By US, ten infants
      (4.5%) with abscess or structural abnormalities other than VUR were diagnosed.
      High-grade (III-V) VUR was present in 39 patients (17.7%). The sensitivities for
      high-grade VUR of renal US alone (76.9%) or DMSA scan alone (82.1%) were not as
      good as that of the "OR rule" strategy, which had 92.3% sensitivity and 94.3%
      negative predictive value. CONCLUSIONS: To screen high-grade VUR in young infants
      with febrile UTI, US and acute DMSA scan could be performed first. VCUG is only
      indicated when abnormalities are apparent on either US or DMSA scan or both.

PMID- 22374406
TI  - New findings on Simalikalactone D, an antimalarial compound from Quassia amara L.
      (Simaroubaceae).
AB  - Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed
      to be an efficient antimalarial all over the Northern part of the Amazon basin.
      Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the
      molecules responsible for the antiplasmodial activity of a watery preparation
      made out of juvenile fresh leaves of this plant. Because of its strong
      antimalarial activity, we decided to have a further insight of SkD
      pharmacological properties, alone or in association with classical antimalarials.
      At concentrations of up to 200MUM, we showed herein that SkD did not exert any
      apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an
      antiproliferative effect was evident at concentrations higher than 45nM. SkD was
      inefficient at inhibiting heme biomineralization and the new permeability
      pathways induced by the parasite in the host erythrocyte membrane. With respect
      to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier
      and later parasite stages, but potently active at the 30th h of parasite cycle
      when DNA replicates in mature trophozoites. In vitro combination studies with
      conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO).
      The activity of ATO on the Plasmodium mitochondrial membrane potential was
      enhanced by SkD, which on its own had a poor effect on this cellular parameter.

PMID- 22374405
TI  - Alternatives to standard unfractionated heparin for pediatric hemodialysis
      treatments.
AB  - Despite advances in biomaterials and dialyzer design, thrombin generation occurs
      in the dialysis circuit because of platelet and leukocyte activation. As such,
      anticoagulation is required by the majority of children for successful dialysis
      to prevent clotting in the venous air detector and the capillary dialyzer,
      particularly for small children with slower blood flow rates. For many years
      unfractionated heparin has been the standard anticoagulant of choice, but is now
      being challenged by low-molecular-weight heparins (LMWHs) because they are simple
      to administer and reliable, particularly as the cost differential has been
      eroded. Alternative, nonheparin anticoagulants are more frequently available, but
      are often restricted to special circumstances: patients at high risk of
      hemorrhage; heparin allergy; or heparin-induced thrombocytopenia. These
      nonheparin alternatives are significantly more expensive than heparins, and may
      add a degree of complexity, such as citrate, which is a regional anticoagulant,
      although citrate-containing dialysate may permit short anticoagulant-free
      dialysis sessions. Systemic anticoagulants required for immune-mediated, heparin
      induced thrombocytopenia are expensive and either have short half-lives, and
      therefore require continuous infusions, or prolonged half-lives, which, although
      allowing simple bolus administration, increases the risk of drug accumulation,
      over-dosage and hemorrhage.

PMID- 22374407
TI  - Could FFAR1 assist insulin secretion in type 2 diabetes?

PMID- 22374408
TI  - TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2,
      randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Activation of free fatty acid receptor 1 (FFAR1; also known as G
      protein-coupled receptor 40) by fatty acids stimulated glucose-dependent beta
      cell insulin secretion in preclinical models. We aimed to assess whether
      selective pharmacological activation of this receptor by TAK-875 in patients with
      type 2 diabetes mellitus improved glycaemic control without hypoglycaemia risk.
      METHODS: We undertook a phase 2, randomised, double-blind, and placebo-controlled
      and active-comparator-controlled trial in outpatients with type 2 diabetes who
      had not responded to diet or metformin treatment. Patients were randomly assigned
      equally to receive placebo, TAK-875 (6.25, 25, 50, 100, or 200 mg), or
      glimepiride (4 mg) once daily for 12 weeks. Patients and investigators were
      masked to treatment assignment. The primary outcome was change in haemoglobin
      A(1c) (HbA(1c)) from baseline. Analysis included all patients randomly assigned
      to treatment groups who received at least one dose of double-blind study drug.
      The trial is registered at ClinicalTrials.gov, NCT01007097. FINDINGS: 426
      patients were randomly assigned to TAK-875 (n=303), placebo (n=61), and
      glimepiride (n=62). At week 12, significant least-squares mean reductions in
      HbA(1c) from baseline occurred in all TAK-875 (ranging from -1.12% [SE 0.113]
      with 50 mg to -0.65% [0.114] with 6.25 mg) and glimepiride (-1.05% [SE 0.111])
      groups versus placebo (-0.13% [SE 0.115]; p value range 0.001 to <0.0001).
      Treatment-emergent hypoglycaemic events were similar in the TAK-875 and placebo
      groups (2% [n=7, all TAK-875 groups] vs 3% [n=2]); significantly higher rates
      were reported in the glimepiride group (19% [n=12]; p value range 0.010-0.002 vs
      all TAK-875 groups). Incidence of treatment-emergent adverse events was similar
      in the TAK-875 overall (49%; n=147, all TAK-875 groups) and placebo groups (48%,
      n=29) and was lower than in the glimepiride group (61%, n=38). INTERPRETATION:
      TAK-875 significantly improved glycaemic control in patients with type 2 diabetes
      with minimum risk of hypoglycaemia. The results show that activation of FFAR1 is
      a viable therapeutic target for treatment of type 2 diabetes. FUNDING: Takeda
      Global Research and Development.

PMID- 22374409
TI  - The un-managed system of Medicare referrals.

PMID- 22374410
TI  - Relationship of electronic medical knowledge resource use and practice
      characteristics with Internal Medicine Maintenance of Certification Examination
      scores.
AB  - BACKGROUND: Maintenance of certification examination performance is associated
      with quality of care. We aimed to examine relationships between electronic
      medical knowledge resource use, practice characteristics and examination scores
      among physicians recertifying in internal medicine. METHODS: We conducted a cross
      sectional study of 3,958 United States physicians who took the Internal Medicine
      Maintenance of Certification Examination (IM-MOCE) between January 1, 2006 and
      December 31, 2008, and who held individual licenses to one or both of two large
      electronic knowledge resource programs. We examined associations between
      physicians' IM-MOCE scores and their days of electronic resource use, practice
      type (private practice, residency teaching clinic, inpatient, nursing home),
      practice model (single or multi-specialty), sex, age, and medical school
      location. RESULTS: In the 365 days prior to the IM-MOCE, physicians used
      electronic resources on a mean (SD, range) of 20.3 (36.5, 0-265) days. In
      multivariate analyses, the number of days of resource use was independently
      associated with increased IM-MOCE scores (0.07-point increase per day of use, p =
      0.02). Increased age was associated with decreased IM-MOCE scores (1.8-point
      decrease per year of age, p < 0.001). Relative to physicians working in private
      practice settings, physicians working in residency teaching clinics and hospital
      inpatient practices had higher IM-MOCE scores by 29.1 and 20.0 points,
      respectively (both p < 0.001). CONCLUSIONS: Frequent use of electronic resources
      was associated with modestly enhanced IM-MOCE performance. Physicians involved in
      residency education clinics and hospital inpatient practices had higher IM-MOCE
      scores than physicians working in private practice settings.

PMID- 22374412
TI  - Gene-Z: a device for point of care genetic testing using a smartphone.
AB  - By 2012, point of care (POC) testing will constitute roughly one third of the $59
      billion in vitro diagnostics market. The ability to carry out multiplexed genetic
      testing and wireless connectivity are emerging as key attributes of future POC
      devices. In this study, an inexpensive, user-friendly and compact device (termed
      Gene-Z) is presented for rapid quantitative detection of multiple genetic markers
      with high sensitivity and specificity. Using a disposable valve-less polymer
      microfluidic chip containing four arrays of 15 reaction wells each with
      dehydrated primers for isothermal amplification, the Gene-Z enables simultaneous
      analysis of four samples, each for multiple genetic markers in parallel,
      requiring only a single pipetting step per sample for dispensing. To drastically
      reduce the cost and size of the real-time detector necessary for quantification,
      loop-mediated isothermal amplification (LAMP) was performed with a high
      concentration of SYTO-81, a non-inhibiting fluorescent DNA binding dye. The Gene
      Z is operated using an iPod Touch, which also receives data and carries out
      automated analysis and reporting via a WiFi interface. This study presents data
      pertaining to performance of the device including sensitivity and reproducibility
      using genomic DNA from Escherichia coli and Staphylococcus aureus. Overall, the
      Gene-Z represents a significant step toward truly inexpensive and compact tools
      for POC genetic testing.

PMID- 22374413
TI  - Cloning and expression analysis of interferon regulatory factor (IRF) 3 and 7 in
      large yellow croaker, Larimichthys crocea.
AB  - The interferon regulatory factor (IRF)3 and IRF7 are considered to play essential
      roles in innate immune system's antiviral responses. In this report, the full
      length cDNA and genomic structure and immune response characterizations of IRF3
      and IRF7 were investigated in large yellow croaker, Larimichthys crocea. The full
      length cDNA of L. crocea (Lc)IRF3 was of 2204 bp, including a 5'-terminal
      untranslated region (UTR) of 41 bp, a 3'-terminal UTR of 774 bp and an open
      reading frame (ORF) of 1389 bp encoding a polypeptide of 462 amino acids
      residues. The full-length cDNA of LcIRF7 was of 1979 bp, including a 5'-terminal
      UTR of 47 bp, a 3'-terminal UTR of 636 bp and an ORF of 1296 bp encoding a
      polypeptide of 431 amino acids. The putative amino acid sequence of both LcIRF3
      and LcIRF7 contained a typical IRF domain at the N-terminal and an IRF3 domain at
      the C-terminal. Furthermore, we obtained 4517 nucleotides (nt) LcIRF3 genome
      sequence based on the full-length cDNA, which contained 11 exons and 10 introns.
      The full-length genome sequence of LcIRF7 was of 3991 nucleotides, including 9
      exons and 8 introns. Quantitative real-time reverse transcription PCR analysis
      revealed a broad expression of LcIRF3 and LcIRF7 with the most predominant
      expression of LcIRF3 and LcIRF7 in the liver and in the gill, respectively. The
      expression levels of LcIRF3 and LcIRF7 after challenged with LPS, poly I:C and
      Vibrio parahaemolyticus were tested in blood, spleen and liver. The results
      showed that the highest relative expression of LcIRF3 was in the liver at 24 h
      after poly I:C injection with 90 times greater than that of the non-injection
      group (p < 0.05). Moreover, LcIRF3 transcription increased significantly at most
      time point in blood and spleen tissue after poly I:C stimulation compared with
      that of the control group. After LPS injection, the peak value of LcIRF7 was in
      the liver with 207 times (at 3 h) as much as that in the control group (p <
      0.05). In addition, LcIRF7 expression was significantly induced by poly I:C
      injection in spleen. Both LcIRF3 and LcIRF7 transcripts did not show significant
      change after V. parahaemolyticus stimulation. These results indicated that IRF3
      and IRF7 might play an important role in large yellow croaker's defense against
      viral and bacterial infection.

PMID- 22374414
TI  - Adaptation of nitrifying microbial biomass to nickel in batch incubations.
AB  - Nitrification-microbial oxidation of ammonia to nitrate-is sensitive to an array
      of inhibitors. Currently, little is known regarding the ecological processes that
      enable adaptation to inhibitors and recovery of nitrification. This study
      evaluated inhibition and recovery of nitrification in batch cultures of activated
      sludge incubated with different levels of nickel (Ni), a model inhibitor.
      Incubation with 1 mg/L of added Ni did not adversely affect nitrification, and
      little inhibition occurred at 5 and 10 mg/L Ni. Incubation with 50 mg/L Ni
      resulted in significant inhibition, decreased amoA transcript abundance, and
      delayed recovery of nitrification until amoA transcript abundance rebounded after
      24 h. For this dosage, recovery of nitrification occurred without a significant
      change in ammonia-oxidizing bacteria (AOB) community structure. By contrast,
      incubation with 150 mg/L of added Ni strongly inhibited nitrification and delayed
      recovery until a shift in AOB community structure occurred after ~6 weeks of
      incubation. The results indicate that inhibitor-resistant nitrifying cultures can
      be obtained from long-term batch incubations of decaying activated sludge
      incubated with high levels of added inhibitor.

PMID- 22374415
TI  - Guiding principles for the implementation of non-animal safety assessment
      approaches for cosmetics: skin sensitisation.
AB  - Characterisation of skin sensitisation potential is a key endpoint for the safety
      assessment of cosmetic ingredients especially when significant dermal exposure to
      an ingredient is expected. At present the mouse local lymph node assay (LLNA)
      remains the 'gold standard' test method for this purpose however non-animal test
      methods are under development that aim to replace the need for new animal test
      data. COLIPA (the European Cosmetics Association) funds an extensive programme of
      skin sensitisation research, method development and method evaluation and helped
      coordinate the early evaluation of the three test methods currently undergoing
      pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to
      what extent skin sensitisation safety assessments for cosmetic ingredients can be
      made in the absence of animal data. In order to propose guiding principles for
      the application and further development of non-animal safety assessment
      strategies it was evaluated how and when non-animal test methods, predictions
      based on physico-chemical properties (including in silico tools), threshold
      concepts and weight-of-evidence based hazard characterisation could be used to
      enable safety decisions. Generation and assessment of potency information from
      alternative tools which at present is predominantly derived from the LLNA is
      considered the future key research area.

PMID- 22374416
TI  - An addendum to injury rates in Iranian taekwondo athletes; a prospective study.
AB  - PURPOSE: The objective of this study was to compare the Iranian taekwondo-in
      statistically in terms of total injury rates to international counterparts as
      gleaned from the extant literature. METHODS: The Iranian sample consisted of 204
      male taekwondo-in participating in the national championship. The international
      sample included the participants in national and international tournaments.
      Validated standard questionnaires were employed at all tournaments to collect
      injury data that were always diagnosed by the respective tournament physicians.
      An injury was defined as any circumstance for which assistance was sought from
      the medical personnel. In addition to injury rates, 95% confidence intervals
      (CIs) around the rates were computed. To assess which group was at higher risk,
      odds ratios were calculated, including the 95%CIs. RESULTS: Compared to Greek
      counterparts, the injury rate for the Iranian taekwondo-in was statistically
      significantly higher. The Iranians were also at a higher risk to incur an injury:
      OR = 11.2 (95%CI: 6.60-18.88, P<0.001, CLR = 2.86). When comparing the Iranian
      taekwondo-in to their colleagues competing at the 1999 World Championships, the
      former recorded a statistically significantly lower injury rate but the latter
      were not at a higher risk (OR = 0.61, 95%CI: 0.41-0.91, P=0.014, CLR = 2.20).
      CONCLUSION: A statistical comparison of total injury rates in Iranian and
      international taekwondo-in revealed no difference between the two groups.
      However, what is of concern is that the total injury rate across taekwondo
      studies is significantly higher than those reported for American football.

PMID- 22374417
TI  - Is there any role for new prognostic markers in breast cancer?

PMID- 22374419
TI  - Castration-resistant metastatic prostate cancer: current status and treatment
      possibilities.
AB  - Prostate cancer (PCa) is the most common cancer in the male population in Western
      countries, second to skin cancer. Hormonal therapy allows long-lasting and
      effective control of cancer-related symptoms in advanced stages; however, in
      almost all patients with metastatic PCa the disease will progress when it becomes
      castration-resistant (CRPC). Chemotherapy with docetaxel was a turning point in
      CRPC, as, for the first time, it resulted in an increased survival time in
      comparison with mitoxantrone and prednisone. Combination therapy with docetaxel
      and prednisone is the first-line treatment of choice. Once the cancer has
      progressed, there is no clear alternative, although some new agents have shown
      promise in the treatment of this type of cancer. This review will provide an
      overview of the current status of CRPC, including clinical status, prognosis,
      firstline treatment and new second-line treatment options.

PMID- 22374418
TI  - Topoisomerase 2 alpha: a real predictor of anthracycline efficacy?
AB  - Anthracyclines are frequently used in the adjuvant setting for breast cancer
      treatment since it is considered that anthracycline-based chemotherapy treatment
      benefits breast cancer patients. Nonetheless, these drugs are associated with
      severe side effects and predictive factors, for sensitivity to anthracyclines,
      are warranted in clinical practice. Topoisomerase 2 alpha (TOP2A) is considered
      to be the molecular target of these drugs. The potential predictive value of
      TOP2A amplification and overexpression has been extensively studied in breast
      cancer patients treated with anthracyclines. However, results are not conclusive.
      In this paper, we review some of the published studies addressing the predictive
      value of TOP2A as well as the cellular functions of this enzyme and its status in
      breast cancer tissue.

PMID- 22374420
TI  - Consensus of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group
      on Brachytherapy in breast cancer.
AB  - Breast cancer is the most frequent neoplasia in women. Randomized studies which
      compare mastectomy with conservative treatment show no differences in global
      survival. In cases in which conservative surgery is performed, breast radiation
      therapy and boost reduces the rate of local recurrence. On March 2010, the 8th
      Consensus Meeting of the Spanish Society for Radiation Oncology (SEOR)
      Brachytherapy Group was held in Madrid about "Treatment of Breast Cancer with
      Brachytherapy". In this article we presented the conclusions about brachytherapy
      boost, Partial breast irradiation and clinical dosimetry.

PMID- 22374421
TI  - Lung cancer chemotherapy decisions in older patients: the role of patient
      preference and interactions with physicians.
AB  - PURPOSE: Lung cancer chemotherapy decisions in patients >= 70 years old are
      complex because of toxicity, comorbidity and the limited data on patient
      preferences. We examined the relationships between preferences and chemotherapy
      use in this group of patients. METHODS AND PATIENTS: We used a questionnaire
      describing four hypothetical lung cancer treatment options. Eighty-three elderly
      (>= 70 years old) lung cancer patients were informed about their diagnosis and
      therapeutic choices and then asked to choose one of the four options. Patients
      had previously been included in a prospective study to explore geriatric
      evaluation in an oncology unit and all had given written informed consent.
      RESULTS: Older patients (n=83) diagnosed with lung cancer (non-small- and small
      cell lung cancer) from January 2006 to February 2008 were recruited from a single
      centre. The mean patient age was 77 years (range: 70-91). Eighty-one patients
      (97.6%) were men. Non-small-cell lung cancer (NSCLC) was the diagnosis in 63
      patients (76%). Most patients selected active treatment (38.6% most survival
      benefit, 18% less survival benefit) and 31.3% selected no active treatment.
      Elderly lung cancer patients were significantly more likely to accept aggressive
      treatments despite high reported toxicities. Although most of the patients were
      symptomatic at diagnosis, the "symptom relief" option was chosen less frequently
      than the options that could prolong survival. Factors significantly related to
      patients' attitude toward chemotherapy were age (p<0.001), frailty (p=0.0039),
      depression and poor performance status (PS). CONCLUSION: Elderly lung cancer
      patients want to be involved in the decision-making process. Survival was the
      main treatment objective for more than half of the patients in this study. We
      have not found other published studies about elderly lung cancer patients'
      decisions about chemotherapy.

PMID- 22374422
TI  - Extracellular matrix metalloproteinase inducer: a novel poor prognostic marker
      for human seminomas.
AB  - OBJECTIVE: Extracellular matrix metalloproteinase inducer (EMMPRIN) is a
      glycosylated member of the immunoglobulin superfamily whose function in human
      seminomas is unknown. We have recently determined that EMMPRIN possesses the
      ability to stimulate fibroblast and endothelial cell matrix metalloproteinase
      production, and that its expression was frequently up-regulated in several
      tumours of the urinary system. Thus, EMMPRIN expression might be associated with
      the progression of human seminomas. The aim of this study was to investigate
      whether the presence of EMMPRIN in seminoma tissues might help to predict the
      patients' prognosis. METHODS: Paraffin-embedded tissues from 65 patients with
      seminomas and 20 normal testes were processed for immunohistochemical staining
      using a mouse monoclonal antibody generated against human EMMPRIN, as primary
      antibody, and a biotinylated goat-anti-mouse IgG, as secondary antibody. In
      addition, the correlation of EMMPRIN expression with clinicopathologic
      characteristics and patients' prognosis was also analysed. RESULTS: EMMPRIN was
      detected in cancerous tissues of 53 patients with seminoma, but not normal
      testes. Thirty- five patients showed weakly to moderately positive and 18
      patients intensely positive expression. Moreover, positive EMMPRIN staining
      correlated significantly with various clinicopathological factors (increased TNM
      stage and higher histological differentiation type) as well as decreased tumour
      specific survival (log-rank, p=0.02). In particular, EMMPRIN expression was an
      independent prognosticator as shown by Cox regression analysis (p<0.001).
      CONCLUSION: EMMPRIN expression in a primary tumour predicts an unfavourable
      prognosis in human seminoma, suggesting its crucial role in the progression of
      this tumour.

PMID- 22374423
TI  - PAX7-FKHR fusion gene inhibits myogenic differentiation via NF-kappaB
      upregulation.
AB  - OBJECTIVE: Alveolar rhabdomyosarcomas (ARMS) are characterised by a PAX3/7-FKHR
      translocation, which is presumed to promote a differentiation arrest in the
      myogenic lineage, in which setting secondary genetic events occur, resulting in
      sarcomagenesis. The aim of this study was to identify the mechanism by which
      PAX3/7-FKHR expression results in a myogenic differentiation block, as discrete
      from the secondary genetic events that complete the sarcomagenic process.
      METHODS: We performed a novel differential gene expression analysis comparing
      normal mesenchymal stem cells with previously generated non-tumorigenic
      mesenchymal stem cells expressing the PAX7-FKHR fusion gene, as well as with a
      known tumorigenic, PAX7-FKHR-expressing ARMS cell line, CW9019. RESULTS: This
      novel analysis uncovered the upregulation of the NF-kappaB pathway as a function
      of PAX3/7-FKHR expression, but distinct from the secondary sarcomagenic process;
      thus implicating NF-kappaB as a mediator of the PAX3/7-FKHR differentiation
      block. We further show that NF-kappaB activity is upregulated in PAX7-FKHR cells
      when compared to parental MSCs due to upregulation of the PI3K/AKT pathway. In
      addition we show that NF-kappaB inhibits myogenesis via activation of cyclinD1/
      cdk4 complexes, which sequester MyoD1, a key myogenic transcription factor.
      CONCLUSIONS: Our results highlight the importance of the NF-kappaB pathway in
      myogenesis and sarcomagenesis and suggest that this pathway may be one of the
      potential therapeutic targets in the treatment of ARMS.

PMID- 22374424
TI  - Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy
      in advanced NSCLC patients.
AB  - INTRODUCTION: The aim of this study was to investigate whe- ther X-ray repair
      cross-complementing group 3 (XRCC3) and xeroderma pigmentosum group D (XPD)
      single nucleotide polymorphism (SNP) affects the outcome of platinum- based
      chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients. MATERIAL
      AND METHODS: From September 2005 to June 2009, 355 advanced-stage NSCLC patients
      were accrued to compare the SNP variants with the outcome of platinum-based
      chemotherapy. TaqMan RT-PCR was used to evaluate the SNPs of the XRCC3 codon241
      (Thr/Met) and XPD codon751 (Lys/Gln) DNA repair genes. RESULTS: There was a lack
      of association between the studied SNPs and the response rate, progression-free
      survival or overall survival (OS) in the whole population. However, subgroup
      analysis revealed that XRCC3 241 Thr/Met or Met/Met allele was associated with
      marginally significantly longer OS than XRCC3 Thr/Thr allele (19.0 m vs. 12.5 m,
      p=0.081) in the patients treated with gemcitabine/ cisplatin or carboplatin
      (GP/GC) while it was correlated with a significantly shorter OS in the patients
      treated with non GP/GC (9.3 m vs. 16 m, p=0.003). XPD751 Lys/Lys had an
      association with statistical significantly longer OS than XPD751 Lys/Gln or
      Gln/Gln in the subgroup of elderly patients (14.10 m vs. 10 m, p=0.019) and
      patients with non-adenocarcinoma (12.6 m vs. 9 m, p=0.042). CONCLUSIONS: XRCC3
      Thr241Met played an opposite role in predicting prognosis of chemotherapy in
      NSCLC patients according to the first-line regimens. XPD 751 Lys/ Lys might be a
      better prognostic marker of elderly or noncarcinoma NSCLC subgroup treated with
      platinum-based chemotherapy.

PMID- 22374425
TI  - Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression
      of glioma and the prognosis of glioblastoma patients.
AB  - OBJECTIVE: The ligand EphrinB2 and the corresponding receptor EphB4 are up
      regulated and involved in tumour growth in various human cancers. However, little
      is known about how this receptor-ligand complex contributes to the progression of
      glioma. This prompted us to study the association between the expressions of
      EphrinB2 and EphB4, clinicopathological variables, and glioma patient outcome.
      METHODS: Immunohistochemical staining was performed to detect the expression
      patterns of EphrinB2 and EphB4 in the biopsies from 96 patients with primary
      gliomas. Kaplan-Meier survival and Cox regression analyses were performed to
      evaluate the prognosis of patients. RESULTS: Immunohistochemical analysis
      revealed that the expression of EphrinB2 was significantly correlated with that
      of EphB4 (r=0.86, p=0.002). EphrinB2 and EphB4 were significantly associated with
      the Karnofsky performance scale (KPS) score and World Health Organization grades
      of patients with gliomas, respectively. Especially, the positive expression rates
      of EphrinB2 and EphB4 were significantly higher in patients with higher grade
      (both p=0.001) and lower KPS score (p=0.002 and 0.003, respectively).
      Multivariate Cox regression analysis revealed that EphrinB2 and EphB4 expressions
      were both independent prognostic factors for progress-free survival of
      glioblastoma patients (both p=0.02). CONCLUSION: Our data indicated for the first
      time that EphrinB2 and EphB4 expressions increase according to the
      histopathological grade and KPS score of glioma, and their expression levels are
      related to the progression-free survival of glioblastoma patients.

PMID- 22374426
TI  - Laryngeal cancer survival in Zaragoza (Spain): a population-based study.
AB  - OBJECTIVE: This article aims to study larynx cancer survival from the Population
      Based Cancer Registry of Zaragoza, Spain, for the period 1978-2002. METHODS: The
      survival rates were calculated using the Kaplan-Meier method. The automated
      calculation of the Catalan Institute of Oncology was utilised to obtain the
      relative survival. RESULTS: The observed survival rate was 84.6% in the first
      year and 60.9% in the fifth year. The one-year relative survival in both genders
      was 86.8% (CI 95%: 85.3-88.4) and 70.1% (CI 95%: 67.8-72.4) after five years.
      Glottic cancer presented a better survival rate than supraglottic and subglottic
      cancers, and a better survival rate was also observed in younger ages. There were
      no statistical differences when comparing survival rates by gender and between
      the periods 1978-1986, 1987-1994 and 1995-2002. CONCLUSIONS: The data suggest
      there were no significant changes in laryngeal cancer survival in the province of
      Zaragoza in the period 1978-2002 and that the tumours located in the glottis
      presented a better prognosis.

PMID- 22374427
TI  - Evaluation of ER-alpha, ER-Beta1 and ER-Beta2 expression and correlation with
      clinicopathologic factors in invasive luminal subtype breast cancers.
AB  - PURPOSE: Luminal subtype breast cancer is defined as oestrogen receptor (ER)-
      and/or progesterone receptor (PR)- positive breast cancer. We detected the
      expression of ER-alpha, ER-Beta1 and ER-Beta2 in the tissue samples of invasive
      luminal subtype breast cancer patients, evaluated the correlations between these
      ER statuses and prognosis, and tried to clarify whether the status of ER-alpha
      isoforms provides clinically useful information further to what is already
      provided by the traditional ER-alpha/PR assay. METHODS: The expression of ER
      alpha, ER-Beta1 and ER-Beta2 in the paraffin-embedded sections of 162 invasive
      luminal subtype breast cancer patients was detected with an immunohistochemical
      staining method. With mid-long-term follow-up, the features of ER-alpha, ER-Beta1
      and ER-Beta2 status and the correlations between clinical characteristics and the
      prognosis were analysed. RESULTS: ER-Beta1-positive status was correlated with PR
      (rs=0.217, p<0.01). The median follow-up time was 92 months (range, 4-98 months).
      Univariate analysis suggested that ER-Beta1 status was significantly correlated
      to diseasefree survival (DFS) time (log rank=3.98, p=0.046), especially in
      patients with positive lymph nodes (log rank=6.20, p=0.013). In patients with
      smaller tumour size (=20 mm), negative ER-Beta2 status was significantly
      correlated to overall survival time (log rank=3.87, p=0.049). CONCLUSIONS: In
      invasive luminal subtype breast cancers, ER-Beta1 is correlated with good
      prognosis and could be regarded as one of the factors for evaluating DFS time,
      especially in lymph node-positive patients. There may be some interactions
      between ER-Beta1 and PR. In clinical practice, besides routine detection of ER
      alpha and PR in invasive luminal subtype breast cancers, immunohistochemical
      staining of ER-Beta1 and ER-Beta2 should be considered in order to achieve more
      useful information. Further studies are needed to confirm our findings.

PMID- 22374428
TI  - Tissue microarray-based study of patients with lymph node-positive breast cancer
      shows tyrosine phosphorylation of signal transducer and activator of
      transcription 3 (tyrosine705-STAT3) is a marker of good prognosis.
AB  - BACKGROUND: Although lymph node-positive breast cancers are associated with
      poorer prognosis, individual patients may have different clinical outcomes.
      Signal transducer and activator of transcription 3 (STAT3) is a point of
      convergence for numerous oncogenic signalling pathways. The goal of this study
      was to determine the prognostic value of phosphorylated (tyrosine705)-STAT3 in
      node-positive breast cancer patients. METHODS: Immunohistochemical analysis of
      Phospho- STAT3 was performed on a tissue microarray of breast cancer specimens.
      The expression pattern of Phospho-STAT3 was correlated with survival outcome, and
      clinical and pathological parameters. RESULTS: Out of 125 interpretable tumours,
      positive Phospho- STAT3 nuclear expression was seen in 35 (28%) of tumours. There
      was no significant relationship between Phospho-STAT3 expression and clinical
      pathological parameters including age, hormonal receptor status, grade and tumour
      size. Interestingly positive tumours had a significantly improved disease-free
      survival at 5 years (p=0.035). Additionally, positive Phospho-STAT3 nuclear
      expression was correlated with significantly improved survival at both 5 years
      (p=0.023) and 10 years (p=0.026). Finally, in multivariate analyses Phospho-STAT3
      was found to be an independent prognostic marker of overall survival in node
      positive breast cancer patients. CONCLUSION: These findings support the role of
      Phospho- STAT3 as an important independent prognostic marker in node-positive
      breast cancer patients.

PMID- 22374429
TI  - Histological ulceration as a prognostic factor in cutaneous melanoma: a study of
      423 cases in Spain.
AB  - INTRODUCTION: Histological ulceration in cutaneous melanoma carries a high risk
      of metastasis and has a poor prognosis. However, some epidemiological and
      survival studies of patients with cutaneous melanoma do not consider histological
      ulceration as one of the main prognostic factors. MATERIALS AND METHODS:
      Epidemiological, clinical, histological and survival characteristics of all
      patients diagnosed with cutaneous melanoma over a 10-year period (1994- 2003)
      were retrospectively analysed. RESULTS: Ulcerated melanoma was observed in 77 of
      423 patients (18.2%). Ulceration was significantly associated with male sex,
      deeper tumour thickness, positive sentinel lymph node biopsy and metastasis
      (p<0.001). Histological ulceration indicates a high relative risk (RR) of death
      from melanoma (RR 9.41; 95% CI 4.52-19.59) and a significant risk of metastasis
      (RR 5.72; 95% CI 3.56-9.19) (p<0.001). CONCLUSIONS: Histological ulceration is
      associated with lower overall survival and disease-free survival in patients with
      cutaneous melanoma. Presence of ulceration must be included in the clinical
      history of patients with melanoma to ensure a careful diagnostic work-up and
      follow-up.

PMID- 22374431
TI  - To intubate or not to intubate: Cornelia de Lange syndrome, ileus and helicopter
      transport.

PMID- 22374430
TI  - The influence of modified pluronic F127 copolymers with higher phase transition
      temperature on arsenic trioxide-releasing properties and toxicity in a
      subcutaneous model of rats.
AB  - Pluronic F127 (PF-127) shows thermoreversible property, which is of the utmost
      interest in optimizing drug formulation and delivery. However, its hitherto
      unresolved drawback of a low phase transition temperature (T (tr)) has limited
      its application in injectable drug delivery systems. We have recently synthesized
      a new type of PF-127 copolymers with higher T (tr) using a simple oxidative
      method. Here, we have investigated the drug-releasing feature of oxidized PF-127
      and oxidized PF-127-containing silver nanoparticles (SNPs), carrying arsenic
      trioxide (ATO), in a subcutaneous model of rats. Injectable hydrogels prepared
      with oxidized PF-127s were less viscous and easier to inject, at the same
      concentration, than their precursor. Addition of SNPs further elevated T (tr),
      resulting in even lower viscosity of the injectable hydrogel prepared from SNP
      containing oxidized PF-127. The oxidized PF-127 copolymers did not differ
      significantly in ATO-releasing ability, compared with parental PF-127, but the
      addition of SNPs altered the ATO-releasing feature of oxidized PF-127 to some
      extent. ATO-carrying oxidized PF-127s had similar toxicity, but the addition of
      SNPs enhanced the hepatotoxicity of ATO, as evidenced by elevated serum levels of
      alanine aminotransferase and aspartate aminotransferase and histological
      alterations, compared to parental PF-127. The results presented herein warrant
      further investigation of the modified PF-127 copolymers to deliver ATO or other
      drugs in the form of injectable hydrogels.

PMID- 22374432
TI  - Dusting right under our nose:  difluoroethane abuse in the emergency department.

PMID- 22374433
TI  - Inhibition of quorum sensing in a computational biofilm simulation.
AB  - Bacteria communicate through small diffusible molecules in a process known as
      quorum sensing. Quorum-sensing inhibitors are compounds which interfere with
      this, providing a potential treatment for infections associated with bacterial
      biofilms. We present an individual-based computational model for a developing
      biofilm. Cells are aggregated into particles for computational efficiency, but
      the quorum-sensing mechanism is modelled as a stochastic process on the level of
      individual cells. Simulations are used to investigate different treatment
      regimens. The response to the addition of inhibitor is found to depend
      significantly on the form of the positive feedback in the quorum-sensing model;
      in cases where the model exhibits bistability, the time at which treatment is
      initiated proves to be critical for the effective prevention of quorum sensing
      and hence potentially of virulence.

PMID- 22374434
TI  - miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute
      liver failure.
AB  - Acute liver failure (ALF) still has an unacceptable high mortality rate, despite
      substantial improvements with multidisciplinary care. The precise underlying
      mechanism of ALF remains to be explored. It has been reported that microRNAs
      (miRNAs) are novel regulators in a number of liver diseases, but the role of
      miRNAs in the development of ALF is not fully understood. An ALF murine model was
      generated by ip injection of D: -GalN/LPS, which was confirmed with
      histopathology and biochemistry. The hepatic miRNA expression profile in ALF was
      determined by microarray and verified by qRT-PCR. The functions and signal
      pathways of the targeted genes of these deregulated miRNAs were predicted, using
      bioinformatics analysis. The possible underlying mechanism was investigated by
      exploring the relationship between miRNA modification and hepatocyte apoptosis.
      There were a total of 95 significantly changed miRNAs in ALF compared to mock
      treated (P < 0.01). Among these 95 miRNAs, 20 were up-regulated and 26 were down
      regulated at both 5 and 7 h time points. Bioinformatics analysis predicted that
      some of these 46 miRNAs were involved in apoptosis. Among the up-regulated miRNAs
      involved in apoptosis, miR-15b and miR-16 showed the highest enrichment and
      targeted the common anti-apoptotic gene, BCL2. Our in vitro data demonstrated
      that miR-15b and/or miR-16 regulated BCL2 at the protein level. Inhibition of miR
      15b and/or miR-16 reduced hepatic apoptosis and TNF production. These data
      suggest that miR-15b and miR-16 regulate TNF mediated hepatic apoptosis via BCL2
      during ALF, and may shed light on the development of a therapeutic strategy for
      treatment of ALF.

PMID- 22374435
TI  - Tailoring of Pd-Pt bimetallic clusters with high stability for oxygen reduction
      reaction.
AB  - The composition-dependent equilibrium structure and thermal stability of Pd-Pt
      clusters with the size of 55 atoms, and CO, O, OH, and O(2) adsorption on these
      clusters have been studied using molecular simulation based on the Gupta
      empirical potential and density functional theory (DFT) calculations. It is found
      that Pd(43)Pt(12) with a three-shell onionlike structure (TS-cluster) exhibits
      the highest relative stability in both DFT and Gupta levels and also the highest
      melting point at the Gupta level among these Pd-Pt clusters. In addition, the
      Pd(43)Pt(12) TS-cluster possesses the weakest CO, O, OH, and O(2) adsorption
      strength, compared to the Pt(55), Pd(55), and Pd(13)Pt(42) clusters, indicating
      good catalytic activities toward the oxygen reduction reaction (ORR) among these
      Pd-Pt clusters considered. We expect that this kind of DFT-guided strategy by
      controlling the composition could provide a simple way for possibly searching new
      electrocatalysts.

PMID- 22374436
TI  - [Therapeutic effect of retinoic acid in lupus nephritis].
AB  - Lupus nephritis is a major cause of morbidity and mortality among patients with
      systemic lupus erythematosus (SLE). In these patients, treatment with
      immunosuppressive agents can significantly improve the outcome of lupus
      nephritis. However, these agents have severe adverse reactions and some patients
      are refractory to those therapies. Retinoids, a group of natural and synthetic
      derivatives of vitamin A, play important regulatory roles of cellular
      proliferation, differentiation and apoptosis. They have been used for the
      treatment of acute promyelocytic leukemia and inflammatory disorders such as
      psoriasis and acne. It has also been shown that retinoids have therapeutic
      effects in various animal models of kidney disease, including lupus nephritis.
      Based on these findings, retinoids are a promising agent for the treatment of
      lupus nephritis. We studied the clinical effects of retinoid therapy in patients
      with lupus nephritis. In open clinical trial, 7 patients with active lupus
      nephritis that was refractory to steroid therapy were studied. In all these
      patients, retinoid was added to the immunosuppressive therapy and its therapeutic
      effects were evaluated. As a result, 4 out of 7 patients showed improvement of
      the clinical symptoms and laboratory findings, including urinary protein and anti
      dsDNA antibody levels. No important adverse effects of ATRA therapy were observed
      in all patients. Thus, retinoids might be indicated in cases of lupus nephritis
      that are refractory to conventional immunosuppressive therapy.

PMID- 22374437
TI  - [Recent findings on phosphoinositide-3 kinase in rheumatic diseases].
AB  - Rheumatic diseases are chronic inflammatory disorders, and many of them are
      autoimmune diseases. Class I phosphatidylinositol-3 kinases (PI3Ks) are enzymes
      that phosphorylate phosphoinositides in response to extracellular stimuli and
      regulates cellular activation, proliferation, and migration, in a variety of cell
      types, suggesting that they play critical roles in the development of
      inflammation. In patients with rheumatic diseases, such as systemic lupus
      erythematosus (SLE) and rheumatoid arthritis (RA), recent reports have shown
      convincing pathogenic evidence for the involvement of PI3K/Akt signaling pathways
      in chronic inflammation. Moreover, selective inhibition of PI3K gamma reduced
      incidence and severity of the renal disease. More recently, the kinome array
      analysis revealed particular up-regulation of PI3K in B cells from patients with
      SLE in comparison with matched controls. Up-regulation of PI3K in T cells was
      also reported in patients with SLE. Further, we have demonstrated anti-rheumatic
      effects of a novel PI3K-specific inhibitor, ZSTK474, in mouse collagen-induced
      arthritis (CIA). Administration of ZSTK474, even if started after the development
      of arthritis, ameliorated CIA with no apparent adverse effect. Proliferation of B
      lymphocytes and synovial fibroblasts were inhibited by ZSTK474 in vitro. ZSTK474
      suppressed osteoclast formation in vitro and also in the joints of CIA mice.
      These findings indicate that PI3K might be a potential therapeutic target of
      rheumatic diseases.

PMID- 22374438
TI  - [Common variable immunodeficiency: an update on etiology, pathophysiology, and
      classification].
AB  - Common variable immunodeficiency is one of the most common primary
      immunodeficiency that is categorized into primary antibody deficiency. The
      responsible genes identified so far include ICOS, TACI, CD19, CD20, CD21, CD81
      and BAFF-R; and most of the CVID-causing genes are yet to be identified. TACI
      mutation is the most common one; however the direct contribution of TACI mutation
      to pathogenesis of CVID is not yet clear. One third to a half of the patients
      with CVID shows autoimmunity as well as malignancy in their course. It is of
      importance to develop diagnostic measure, to identify the disease causing genes,
      and to develop the optimal therapy.

PMID- 22374439
TI  - [An approach to the patients with cryopyrin-associated periodic syndrome (CAPS) :
      a new biologic response modifier, canakinumab].
AB  - Cryopyrin-associated periodic syndrome (CAPS) comprises a group of rare, but
      severe, autoinflammatory syndrome, and includes 3 distinct conditions, familial
      cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal
      onset multisystem inflammatory disease (MONID). These syndromes are characterized
      by urticarial-like rash, periodic fever, central nervous system inflammation, an
      arthropathy, and the risk of amyloidosis. About 20% die by age 20 years in the
      most severe cases. The disease is associated with mutations in the NLRP3 gene
      that encodes for the protein cryopyrin, a component of the inflammasome complex
      that regulates the production and secretion of IL-1beta. Canakinumab is a human
      IgG monoclonal antibody targeting IL-1beta. The clinical trials of canakinumab
      for patients with CAPS in both western countries and Japan were well-tolerated in
      most patients, and provided significant advantages over existing competitive
      therapies. Although no serious adverse effects have been reported, the
      frequencies of common infectious diseases including nasopharyngitis, upper
      respiratory tract infections, and gastroenteritis were reported presumably due to
      the blockade of proinflammatory cytokine, IL-1beta. For us pediatrician, it will
      be important to be more careful for infectious diseases to provide the maximum
      safety of canakinumab for these patients.

PMID- 22374440
TI  - [Usefulness of measuring serum IgG4 level as diagnostic and treatment marker in
      IgG4-related disease].
AB  - IgG4-related disease is a chronic disorder, which is characterized with elevated
      levels of serum immunoglobulin (Ig)G4 and abundant infiltration of IgG4-positive
      plasmacyte and storiform fibrosis in the enlarged organs. It includes Mikulicz's
      disease (IgG4-related dacryoadenitis and sialadenitis), autoimmune pancreatitis
      type I, and so on. In Japan, we have been able to measure the IgG4 levels in our
      clinic since 2010, and we knew that various diseases except IgG4-related disease,
      also presented with elevated levels of serum IgG4. Eosinopihic disorders, such as
      Chrug-Strauss syndrome, a part of rheumatoid arthritis and systemic sclerosis can
      present with high levels of serum IgG4. So the confusion is seen in some
      clinicians, but we have to recognize that only serological findings cannot lead
      to the correct diagnosis in IgG4-related disease. The pathological and image
      findings also are needed. With regard of the treatments for IgG4-related disease,
      the levels of serum IgG4 often reflected with the therapeutic response, and were
      also the markers, which predicted the relapse. We describe herein the
      significance of measuring serum IgG4 levels in the diagnosis and during the
      treatment for IgG4-related disease.

PMID- 22374441
TI  - [BCMA and autoantibody-producing RP105 B cells; possible new targets of B cell
      therapy in systemic lupus erythematosus].
AB  - Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease
      with multiple organ disorders. Although the prognosis of SLE has been recently
      improved, corticosteroid and immunosuppressive agents are still main treatment
      used in medical practice. Refractory disease and complications by the
      conventional drugs still remain. RP105 (CD180) is one of the toll-like receptor
      associated molecules. The molecule is expressed on mature B cells. Significantly
      increased population of RP105-negative [RP105(-)] B cells is found in SLE. RP105(
      ) B cells belong to highly activated and differentiated late B cells and produce
      autoantibodies including anti-dsDNA antibodies. RP105(-) B cells are further
      divided into at least 5 subsets that include novel human B cell subsets. In
      active SLE, subset 1 (activated B cells) and 3 (early-plasmablasts) are
      significantly increased compared to inactive SLE patients. Especially, subset 3
      RP105(-) B cells may play an important role in pathophysiology of SLE. RP105(-) B
      cells from active SLE patients express preferentially BCMA (B-cell maturation
      antigen) compared to BAFF-R (B-cell activating factor-receptor) than normal
      subjects and other autoimmune diseases. In SLE, it is suggested that BAFF/APRIL
      (a proliferation-inducing ligand) maintain chronic activation and survival of
      RP105(-) B cells. The increased RP105(-) B cells may reflect the breaking of
      tolerance checkpoint for autoreactive B cells and finally affect autoimmunity in
      SLE. For the B cell therapy, especially targeting of autoantibody-producing B
      cells, including subset 3 of RP105(-) B cells, BCMA and RP105(-) B cell itself
      may be an ideal target.

PMID- 22374442
TI  - [Autoantigen BiP and autoimmune diseases].
AB  - Immunoglobulin Binding Protein (BiP) is a member of heat shock protein 70
      famaily, and is also known as an autoantigen in rheumatoid arthritis (RA)
      patients. Serum anti-BiP antibody is detected up to 60% of RA patients, and
      recent reports demonstrated that serum anti-BiP antibody is also detected in
      systemic lupus erythematosus patients. Notably, anti-citrullinated BiP antibody
      is revealed as another member of anti-citrullinated protein/peptide antibodies
      (ACPAs). Since ACPAs are supposed to be closely associated with RA pathogenesis,
      immune responses to citrullinated BiP could play an important role in RA. Indeed,
      immunization of citrullinated BiP exacerbated inflammatory arthritis in mice.
      Moreover, T cell responses to BiP were reported in human RA and mice models. In
      mice models, native BiP administration induced IL-4 and IL-10 producing CD4(+) T
      cells and regulated inflammatory arthritis. In this way, immune responses to BiP
      are various, and dysregulation of the balances between pro-inflammatory and
      regulatory responses to BiP could lead to the autoimmune responses and diseases.

PMID- 22374443
TI  - [Crucial role of TNFalpha-induced adipose-related protein (TIARP) in the
      pathogenesis of autoimmune arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a variable
      disease outcome, and is characterized by inflammation of multiple joints.
      Proinflammtory cytokines, such as tumor necrosis factor alpha (TNFalpha),
      interleukin-6 (IL-6) are thought to play crucial roles in the pathology of RA.
      The prognosis of patients with RA has improved significantly with the recent
      availability of biologics targeting TNFalpha and IL-6. Immunization of DBA/1 mice
      with glucose-6-phosphate isomerase (GPI) induces severe acute arthritis. This
      arthritis can be controlled by TNFalpha antagonists, suggesting similar etiology
      to RA. We performed GeneChip analysis using splenocytes of mice with GPI-induced
      arthritis. Among the arrayed TNFalpha-related genes, the expression of TNFalpha
      induced adipose-related protein (TIARP) mRNA was the highest. TIARP was detected
      specifically in joints and spleens of arthritic mice. Among the splenocytes,
      CD11b(+) cells were the main source of TIARP mRNA. STEAP4 (the human ortholog of
      TIARP) was highly upregulated in joints of patients with RA and especially co
      localized with CD68(+) macrophages. In this study, we discuss the role of TIARP
      in the generation of experimental autoimmune arthritis and the possible clinical
      application of for the treatment of RA.

PMID- 22374444
TI  - [Involvement of Syk in pathology of systemic autoimmune disease].
AB  - Biological products have proven its high efficacy on autoimmune disease such as
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile,
      small molecular drugs have attracted attention over the years because of its
      availability of oral administration and cost effectiveness. Spleen tyrosine
      kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that
      are involved in the immune system and inflammation such as B cells, T cells,
      macrophages and synovial fibroblast. Syk is involved in intracellular signaling
      of the multi-chain immune receptors, including B cell receptor (BCR), zetachain
      of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor
      tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has
      exerted potent therapeutic efficacy against autoimmune and allergic diseases such
      as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura
      (ITP). Moreover, Syk blockade prevented the development of skin and kidney
      lesions in lupus-prone mice, however the mechanism of action is unclear. We have
      revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of
      toll-like receptor (TLR)-9, thereby allowing efficient propagation of CD40- and
      TLR9- signaling in human B cells. These results indicate that inhibition of Syk
      have a potential to regulate B-cell mediated inflammatory diseases such as SLE.
      We here document the in vitro and in vivo effects of a Syk inhibitor for the
      treatment of autoimmune diseases, mainly in RA and SLE.

PMID- 22374445
TI  - [Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells].
AB  - Dendritic cells (DCs) is the cell that act as source of the immune response by
      exquisitely presenting antigens to acquired immunity such as the T cells. Janus
      kinase (JAK) is a tyrosine kinase that is activated immediately after the
      cytokine binds to its unique receptor expressed on the cell surface. Among the
      JAKs, expression of JAK3 is limited on haematopoietic cells and is indispensable
      for lymphocyte development and proliferation. We have demonstrated that JAK3
      deficient DCs normally develop, uptake antigens, produce inflammatory cytokines
      and function as an antigen-presenting cell, although they over-produce IL-10.
      Among the transcription factors that are known to be activated by JAK3, we
      explored the phenotype of Stat6-deficient DCs which is a transcription factor
      specifically activated by JAK3. Interestingly, development, function and
      inflammatory cytokine production was normal with over-production of IL-10 which
      was in line with the JAK3-deficient DCs. IL-4 is well known to activate JAK3
      Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid
      of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL
      4 can be considered as one of the inflammatory process of arthritis. Moreover,
      induction of IL-10 production by DCs can be one mechanism of action of the JAK
      inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid
      arthritis in clinical trials.

PMID- 22374446
TI  - [Role of microRNA in rheumatoid arthritis].
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs of approximately 22
      nucleotides in length. miRNAs repress expression of target genes at the
      posttranscription level. Biological relevance of miRNAs have been investigated in
      physiological and pathological conditions, revealing their involvement in fine
      tuning of the biological events, such as cell proliferation, differentiation and
      cell death. In 2008, miR-146a and miR-155 were reported to be involved in the
      pathology of rheumatoid arthritis. Subsequently, expression and function of other
      miRNAs in rheumatoid arthritis have been reported. These reports suggest that
      miRNAs could be novel candidates for the therapeutic target or biomarker of
      rheumatoid arthritis. Further investigations are required to identify,
      characterize and modulate the key miRNA in the pathology of rheumatoid arthritis.

PMID- 22374447
TI  - [Impaired expression of Act1mRNA in B cells of patients with Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disorder characterized by
      profound lymphocytic infiltration into the lacrimal and salivary glands, thereby
      diminished secretory function. B cell hyper-activation is a predominant feature
      of SS related to hypergammaglobulinemia and production of autoantibodies. The
      adaptor molecule NF-kB activator 1 (Act1) plays an important role in the
      homeostasis of B cells by attenuating CD40 and B cell-activating factor belonging
      to the tumor necrosis factor family receptor (BAFFR) signaling. Act1-deficient
      mice develop autoimmune manifestations similar to SS, which are
      hypergammaglobulinemia, high levels of anti-SSA and anti-SSB autoantibodies. In
      this study, to investigate the role of Act1 in the pathogenesis of SS, we
      examined Act1mRNA expressions in B cells from patients with SS and discussed the
      association of Act1 with parameters and clinical manifestations of SS. We showed
      the low level of Act1mRNA expression in patients with SS and reciprocal
      association of Act1 with serum IgG level. Diminished Act1mRNA expression in SS
      may be associated with B cell hyperactivity and elevated immunoglobulin
      production in SS by uncontrolled B cell activation signal through CD40 and BAFFR.

PMID- 22374448
TI  - [Blockade of Triggering receptor expressed on myeloid cells-1 as a new therapy of
      arthritis].
AB  - Triggering receptor expressed on myeloid cells (TREM)-1 belongs to an
      immunoglobulin super family and is expressed on neutrophils, mature monocytes and
      macrophages. The engagement of TREM-1 synergizes with several Toll Like Receptors
      (TLR) activation in amplifying the inflammatory response. TREM-1 blockade using a
      fusion protein containing murine TREM-1 extracellular domain and human
      immunoglobulin Fc portion was reported to prevent death in mouse models of
      microbial peritonitis and protect from organ damage during other inflammatory
      diseases. There are many reports suggesting the involvement of TREM-1 in the
      pathogenesis of rheumatoid arthritis. Blockade of TREM-1 could be a new
      therapeutic target in rheumatoid arthritis without impairing the host defense
      against microbes. In this report, we outline the role of TREM-1 and the trial of
      developing anti-rheumatic drugs by targeting its ligand.

PMID- 22374449
TI  - [Neonatal herpes simplex type II virus infection complicated with meningitis and
      virus-associated hemophagocytic syndrome].
AB  - A 14-day-old neonate was transferred to our university hospital because of
      respiratory distress and mild disturbance of consciousness. He had no history of
      abnormal pregnancy or delivery, but had developed apnea at 6 days old.
      Thereafter, respiratory distress progressed and his condition deteriorated. On
      admission to our hospital, several vesicles were found on the left upper arm, and
      moderate hepatomegaly was also present. Herpes simplex virus (HSV) type II genome
      was detected from serum, spinal fluid, and bone marrow. Laboratory examinations
      revealed typical abnormalities of disseminated intravascular coagulation,
      increased levels of serum ferritin, aspartate aminotransferase, and lactate
      dehydrogenase. Bone marrow aspiration demonstrated activated macrophages and
      hemophagocytosis. Spinal tap revealed numerous mononuclear cells. Meningitis and
      virus-associated hemophagocytic syndrome (VAHS) due to systemic HSV type II
      infection were thus diagnosed. Acyclovir (60 mg/kg/day) and vidarabine were
      promptly administered. Dexamethasone palmitate and intravenous cyclosporine were
      also administered for systemic inflammation due to VAHS. Finally, these
      aggressive therapies rescued the patient without any sequelae. In general,
      neonatal systemic HSV infection is life-threatening and results in poor intact
      survival. Our case report suggests that not only antiviral treatment for HSV, but
      also anti-inflammatory treatment including steroid and cyclosporine should be
      considered from the early phase of neonatal systemic HSV infection.

PMID- 22374450
TI  - [Successful early treatment in a case of Cogan's syndrome].
AB  - We report a 53-year-old male with Cogan's syndrome. He was admitted to our
      hospital because of a fever of 2-weeks duration, blurred vision for 10 days,
      hypoacusis, and numbness of the left hand for 3 days. In addition to uveitis,
      hypoacusis, and aseptic meningitis, multiple mononeuropathy was diagnosed based
      on a nerve conduction study. Furthermore, positron emission tomography/computed
      tomography (PET/CT) revealed diffuse aortitis. Accordingly, the patient was
      diagnosed with Cogan's syndrome. After starting steroid-pulse therapy followed by
      1 mg oral prednisolone/kg/day, the uveitis and hypoacusis improved immediately,
      while the peripheral neuropathy persisted until effectively treated with
      intravenous gamma globulin therapy. Prompt steroid therapy for Cogan's syndrome
      based on a diagnosis made using PET/CT prevented progression of the hypoacusis.

PMID- 22374452
TI  - Intramolecular 1,3-dipolar cycloaddition reactions in the synthesis of complex
      annelated quinolines, alpha-carbolines and coumarins.
AB  - In this study, we report the synthesis of several novel dihydroisoxazole-,
      tetrahydroisoxazole- and dihydropyrazole-fused pyrido[2,3-b]quinolines, alpha
      carbolines, and pyrido[2,3-c]coumarins, respectively, from simple precursors and
      by exploring intramolecular 1,3-dipolar cycloaddition reactions involving nitrile
      oxides, nitrones, and nitrile imines as 1,3-dipoles.

PMID- 22374453
TI  - Climate change impact on development rates of the codling moth (Cydia pomonella
      L.) in the Wielkopolska region, Poland.
AB  - The main goal of this paper is to estimate how the observed and predicted climate
      changes may affect the development rates and emergence of the codling moth in the
      southern part of the Wielkopolska region in Poland. In order to simulate the
      future climate conditions one of the most frequently used A1B SRES scenarios and
      two different IPCC climate models (HadCM3 and GISS modelE) are considered. A
      daily weather generator (WGENK) was used to generate temperature values for
      present and future climate conditions (time horizons 2020-2040 and 2040-2060).
      Based on the generated data set, the degree-days values were then calculated and
      the emergence dates of the codling moth at key stages were estimated basing on
      the defined thresholds. Our analyses showed that the average air surface
      temperature in the Wielkopolska region may increase from 2.8 degrees C (according
      to GISS modelE) even up to 3.3 degrees C (HadCM3) in the period of 2040-2060.
      With the warming climate conditions the cumulated degree-days values may increase
      at a rate of about 142 DD per decade when the low temperature threshold (T(low))
      of 0 degrees C is considered and 91 DD per decade when T(low) = 10 degrees C. The
      key developmental stages of the codling moth may occur much earlier in the future
      climate conditions than currently, at a rate of about 3.8-6.8 days per decade,
      depending on the considered GCM model and the pest developmental stage. The
      fastest changes may be observed in the emergence dates of 95% of larvae of the
      second codling moth generation. This could increase the emergence probability of
      the pest third generation that has not currently occurred in Poland.

PMID- 22374454
TI  - Mussel-inspired silver-releasing antibacterial hydrogels.
AB  - A silver-releasing antibacterial hydrogel was developed that simultaneously
      allowed for silver nanoparticle formation and gel curing. Water-soluble
      polyethylene glycol (PEG) polymers were synthesized that contain reactive
      catechol moieties, inspired by mussel adhesive proteins, where the catechol
      containing amino acid 3,4-dihydroxyphenylalanine (DOPA) plays an important role
      in the ability of the mussel to adhere to almost any surface in an aqueous
      environment. We utilized silver nitrate to oxidize polymer catechols, leading to
      covalent cross-linking and hydrogel formation with simultaneous reduction of
      Ag(I). Silver release was sustained for periods of at least two weeks in PBS
      solution. Hydrogels were found to inhibit bacterial growth, consistent with the
      well-known antibacterial properties of silver, while not significantly affecting
      mammalian cell viability. In addition, thin hydrogel films were found to resist
      bacterial and mammalian cell attachment, consistent with the antifouling
      properties of PEG. We believe these materials have a strong potential for
      antibacterial biomaterial coatings and tissue adhesives, due to the material
      independent adhesive properties of catechols.

PMID- 22374455
TI  - Prevention of colorectal cancer liver metastasis by exploiting liver immunity via
      chitosan-TPP/nanoparticles formulated with IL-12.
AB  - The development of effective therapies for the prevention of colorectal cancer
      (CRC) liver metastasis is of great importance. Recently, chitosan (CS)
      nanoparticles have been utilized as carriers of interluekin-12 (IL-12)
      administered locally to deliver therapeutic proteins and genes. In this study, we
      encapsulated IL-12 by incorporation using tripolyphosphate (TPP) as the
      coacervated crosslinking agent to form CS-TPP/IL-12 nanoparticles. We further
      characterized the association efficiency, rate of release, liver-targeting, and
      toxicity, which were predominantly dependent on the factors of particle size,
      zeta potential, pH of solution, and whether or not modified with TPP. Systemic
      delivery of CS-TPP/IL-12 nanoparticles significantly reduced the number and
      volume of CRC liver metastasis foci compared to the CS-TPP treated mouse group.
      Although delivery of IL-12 alone also inhibited the number of CRC liver
      metastasis observed, further study of the change in hepatic metastasis volume
      demonstrated no significant differences between the groups treated with CS-TPP or
      IL-12 alone. Mechanistically, CS-TPP nanoparticles blocked the toxicity of IL-12
      and induced infiltration of NK cells and some T cells, which are most likely the
      effector cells that mediate tumor metastasis inhibition during CS-TPP/IL-12
      immunotherapy. The results obtained from this study demonstrate the potential
      benefit of using chitosan modification technology as a cytokine delivery system
      for the successful prevention of CRC liver metastasis by exploiting liver
      immunity.

PMID- 22374456
TI  - An epirubicin-conjugated nanocarrier with MRI function to overcome lethal
      multidrug-resistant bladder cancer.
AB  - Multidrug resistance (MDR) presents a major obstacle to curing cancer.
      Chemotherapy failure can occur through both cell membrane drug resistance (CMDR)
      and nuclear drug resistance (NDR), and anticancer effectiveness of
      chemotherapeutic agents is especially reduced by their nuclear export. Here we
      report an exciting magnetically-targeted nanomedicine formed by conjugation of
      epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC).
      Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell
      models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides,
      the half-life of drug is prolonged ~1.8-fold (from 45 h to 81 h) at 37  degrees
      C, with a ~10-fold increase in concentration at the tumor site through magnetic
      targeting (MT). Moreover, malignant NDR bladder cancer can be effectively
      inhibited after 14 days in mice by just two injections and MT. We are the first
      to demonstrate the nanomedical strategy that can overcome the CMDR and NDR
      bladder cancers simultaneously, and proceed to the excellent MT therapy,
      significantly reducing the dosage and cardiotoxicity and holding great promise
      for incurable human MDR bladder cancer.

PMID- 22374457
TI  - NSAID-PPI enteropathy in humans.

PMID- 22374459
TI  - The cost-effectiveness of screening lung cancer patients for targeted drug
      sensitivity markers.
AB  - BACKGROUND: New oncology drugs are being developed in conjunction with companion
      diagnostics with approval restricting their use to certain biomarker-positive
      subgroups. We examined the impact of different predictive biomarker screening
      techniques and population enrichment criteria on the cost-effectiveness of
      targeted drugs in lung cancer, using ALK and crizotinib to build the initial
      model. METHODS: Health economic modeling of cost per Quality Adjusted Life Year
      was based on literature review and expert opinion. The modeled population
      represented advanced non-small cell lung cancer (NSCLC), eligible for predictive
      biomarker screening with prescribing restricted to biomarker-positive patients.
      RESULTS: For assays costing $1400 per person, cost per quality-adjusted life year
      (QALY) gained for ALK screening all advanced NSCLC, excluding treatment cost, is
      $106,707. This falls to $4756 when only a highly enriched population is screened
      (increasing biomarker frequency from 1.6 to 35.9%). However, the same enrichment
      involves missing 56% patients who segregate within the unscreened group. Cheaper
      screening tests that miss some true positives can be more cost-effective if
      proportional reductions in cost exceed proportion of subjects missed. Generic
      modeling of idealised screening assays, including treatment cost, reveals a
      dominant effect of screening cost per person at low biomarker frequencies. Cost
      effectiveness of <$100,000 per QALY gained is not achievable at biomarker
      frequencies <5% (with drug costs $1-5000 per month and screening costs $600-1400
      per person). INTERPRETATION: Cost-effectiveness of oncology drugs whose
      prescribing is restricted to biomarker-positive subgroups should address the cost
      of detecting marker-positive patients. The cost of screening dominates at low
      frequencies and strategies to improve cost-effectiveness based on the assay cost,
      drug cost and the group screened should be considered in these scenarios.

PMID- 22374460
TI  - Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2
      overexpressing metastatic pancreatic cancer.
AB  - BACKGROUND: New therapeutic options for metastatic pancreatic cancer are urgently
      needed. In pancreatic cancer, overexpression of the epidermal growth factor
      receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study
      investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined
      with capecitabine in the patients with pancreatic cancer and HER2 overexpression.
      METHODS: Primary endpoint was progression-free survival (PFS) after 12 weeks. A
      total of 212 patients were screened for HER2 expression. RESULTS:
      Immunohistochemical (IHC) HER2 expression was: 83 (40%) grade 0, 71 (34%) grade
      1, 31 (15%) grade 2, 22 (11%) grade 3. A total of 17 patients with IHC +3 HER2
      expression or gene amplification could be assessed for the treatment response.
      Grade 3/4 treatment toxicities were: each 7% leucopenia, diarrhoea, nausea and
      hand-foot syndrome. Progression-free survival after 12 weeks was 23.5%, median
      overall survival (OS) 6.9 months. CONCLUSION: This study demonstrates +3 HER2
      expression or gene amplification in 11% of patients. Contrary to breast and
      gastric cancer, only 7 out of 11 (64%) patients with IHC +3 HER2 expression
      showed gene amplification. Although the therapy was well tolerated, PFS and OS
      did not perform favourably compared with standard chemotherapy. Together, we do
      not recommend further evaluation of anti-HER2 treatment in patients with
      metastatic pancreatic cancer.

PMID- 22374461
TI  - Uterine artery pulsatility index: a predictor of methotrexate resistance in
      gestational trophoblastic neoplasia.
AB  - BACKGROUND: Neo-angiogenesis is a hallmark of cancer. The aim of this study was
      to test the hypothesis, in a prospective patient cohort, that in low-risk
      gestational trophoblastic neoplasia (LR-GTN) the uterine artery pulsatility index
      (UAPI), a measure of tumour vascularity, can predict resistance to methotrexate
      chemotherapy (MTX-R). METHODS: 286 LR-GTN patients (Charing Cross Hospital (CXH)
      score 0-8, or FIGO score 0-6) were treated with methotrexate between January 2008
      and June 2011 at CXH. During staging investigations, patients underwent a Doppler
      ultrasound to assess the UAPI. RESULTS: 239 patients were assessable for both
      UAPI and MTX-R. The median UAPI was lower (higher vascularity) in MTX-R compared
      with MTX-sensitive patients (0.8 vs 1.4, P<0.0001). In multivariate logistic
      regression, UAPI<=1 predicted MTX-R, independent of both CXH and FIGO scores. The
      risk of MTX-R in patients with a FIGO score of 6 and UAPI<=1 was 100% vs 20% in
      patients with UAPI>1 (chi(2) P<0.0001). CONCLUSION: UAPI represents an
      independently validated clinically useful predictor of MTX-R in LR-GTN. Further,
      consideration of whether to incorporate UAPI into the FIGO scoring system is now
      warranted so that patients with a score of 6 and a UAPI <=1 might be upstaged and
      offered combination chemotherapy rather than MTX.

PMID- 22374462
TI  - The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows
      for MHC-independent immune targeting.
AB  - BACKGROUND: Novel treatment strategies are needed to cure disseminated Ewing
      sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin
      are both compatible with aberrant expression of the ganglioside antigen G(D2) and
      led us to explore G(D2) immune targeting in this cancer. METHODS: We investigated
      G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then
      assessed the antitumour activity of T cells expressing a chimeric antigen
      receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo. RESULTS:
      Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of
      3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had
      uniform G(D2) expression. T cells specifically modified to express the G(D2)
      specific chimeric receptor 14. G2a-28zeta efficiently interacted with Ewing
      sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover,
      chimeric receptor gene-modified T cells from healthy donors and from a patient
      exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous
      Ewing sarcoma, including tumour cells grown as multicellular, anchorage
      independent spheres. G(D2)-specific T cells further had activity against Ewing
      sarcoma xenografts. CONCLUSION: G(D2) surface expression is a characteristic of
      Ewing sarcomas and provides a suitable target antigen for immunotherapeutic
      strategies to eradicate micrometastatic cells and prevent relapse in high-risk
      disease.

PMID- 22374463
TI  - Cancer-specific survival after radical nephroureterectomy for upper urinary tract
      urothelial carcinoma: proposal and multi-institutional validation of a post
      operative nomogram.
AB  - BACKGROUND: Owing to the scarcity of upper urinary tract urothelial carcinoma
      (UUT-UC) it is often necessary for investigators to pool data. A patient-specific
      survival nomogram based on such data is needed to predict cancer-specific
      survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a
      nomogram to predict CSS post NU. PATIENTS AND METHODS: Twenty-one French
      institutions contributed data on 1120 patients treated with NU for UUT-UC. A
      total of 667 had full data for nomogram development. Study population was divided
      into the nomogram development cohort (397) and external validation cohort (270).
      Cox proportional hazards regression models were used for univariate and
      multivariate analyses and to build a nomogram. A reduced model selection was
      performed using a backward step-down selection process, and Harrell's concordance
      index (c-index) was used for quantifying the nomogram accuracy. Internal
      validation was performed by bootstrapping and the reduced nomogram model was
      calibrated. RESULTS: Of the 397 patients in the nomogram development cohort, 91
      (22.9%) died during follow-up, of which 66 (72.5%) died as a consequence of UUT
      UC. The actuarial CSS probability at 5 years was 0.76 (95% CI, 71.62-80.94). On
      multivariate analysis, T stage (P<0.0001), N status (P=0.014), grade (P=0.026),
      age (P=0.005) and location (P=0.022) were associated with CSS. The reduced
      nomogram model had an accuracy of 0.78. We propose a nomogram to predict 3 and 5
      year CSS post NU for UUT-UC. CONCLUSION: We have devised and validated an
      accurate nomogram (78%), superior to any single clinical variable or current
      model, for predicting 5-year CSS post NU for UUT-UC.

PMID- 22374464
TI  - Increasing response rates from physicians in oncology research: a structured
      literature review and data from a recent physician survey.
AB  - Although the physician survey has become an important tool for oncology-focused
      health services research, such surveys often achieve low response rates. This
      mini-review reports the results of a structured review of the literature relating
      to increasing response rates for physician surveys, as well as our own experience
      from a survey of physicians as to their referral practices for suspected
      haematologic malignancy in the United States. PubMed and PsychINFO databases were
      used to identify methodological articles assessing factors that influence
      response rates for physician surveys; the results were tabulated and reviewed for
      trends. We also analysed the impact of a follow-up telephone call by a physician
      investigator to initial non-responders in our own mailed physician survey,
      comparing the characteristics of those who responded before vs after the call.
      The systematic review suggested that monetary incentives and paper (vs web or
      email) surveys increase response rates. In our own survey, follow-up telephone
      calls increased the response rate from 43.7% to 70.5%, with little discernible
      difference in the characteristics of early vs later responders. We conclude that
      in addition to monetary incentives and paper surveys, physician-to-physician
      follow-up telephone calls are an effective method to increase response rates in
      oncology-focused physician surveys.

PMID- 22374465
TI  - Biglycan is a specific marker and an autocrine angiogenic factor of tumour
      endothelial cells.
AB  - BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their
      abnormalities, compared gene expression profiles of TECs and normal endothelial
      cells (NECs) by microarray analysis and identified several genes upregulated in
      TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat
      proteoglycan. No report is available on biglycan expression or function in TECs.
      METHODS: The NEC and TEC were isolated. We investigated the biglycan expression
      and function in TECs. Western blotting analysis of biglycan was performed on sera
      from cancer patients. RESULTS: Biglycan expression levels were higher in TECs
      than in NECs. Biglycan knockdown inhibited cell migration and caused
      morphological changes in TECs. Furthermore, immunostaining revealed strong
      biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan
      was detected in the sera of cancer patients but was hardly detected in those of
      healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel
      TEC marker and a target for anti-angiogenic therapy.

PMID- 22374467
TI  - The restructuring of dopamine receptor subtype gene transcripts in c-fos KO mice.
AB  - Although c-Fos protein is one of the principal molecules in intracellular
      signaling, c-fos gene disruption is associated with alterations in neuronal
      functions that do not correspond to its importance in function. The aim of the
      study was to evaluate the changes of dopaminergic system together with
      acetylcholinesterase (AChE) in c-fos disruption (KO). KO male mice showed an
      increase in D1-like receptor (279% of WT) and D2-like receptor (345% of WT)
      binding sites in the cortex. On the gene expression level (assessed by real-time
      PCR), lower quantities of D1R-mRNA (0.64) and D5R-mRNA (0.6) were found in
      females when compared to males in the frontal cortex, higher D2R-mRNA in the
      parietal (1.43) and temporal (2.64) cortex and lower AChE-mRNA (0.67). On the
      contrary, female striatum contained higher level of D2R-mRNA (1.62) and AChE-mRNA
      (1.57) but lower level of D3R-mRNA (0.73). Hypothalamic D1R-mRNA, D2R-mRNA and
      D4R-mRNA were higher in females (1.38, 1.63, and 1.68, respectively). Disruption
      of c-fos increased selectively D5R-mRNA (1.31) in male parietal cortex, D2R-mRNA
      (1.72) in male temporal cortex, and cerebellar D2R-mRNA in both males (1.43) and
      females (1.42), respectively. In females, we found rather decrease in DR-mRNA.
      Multiple correlations in mRNA quantities (in WT mice) were found, which changed
      considerably upon c-fos KO. Main interactions in WT were inter-regional, CNS of
      KO underwent an extensive restructuring comprising intraregional interactions in
      the frontal cortex, hypothalamus, and cerebellum. These changes in DR (between
      others) could be considered as one of the adaptive mechanisms in c-fos KO mice.

PMID- 22374468
TI  - The effects of nizatidine on transient lower esophageal sphincter relaxations
      (TLESRs) and acid reflux in healthy subjects.
AB  - BACKGROUND: A study in Japan has found that nizatidine (NIZ) is more effective
      than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis
      (RE), although the NIZ group included a greater number of patients with severe
      RE. As there was no difference in the level of acid suppression among H2RAs, it
      is possible that NIZ has other effects on esophageal acid exposure (EAE) besides
      acid suppression. In this study, the effect of NIZ on transient lower esophageal
      sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects.
      METHODS: In 10 healthy subjects, while in a sitting position, esophageal motility
      and a pH study were measured for 3 hours after a meal on 2 separate days at least
      2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before
      the meal on one day and a placebo on the other. Both studies were preceded by a
      week of treatment with either NIZ (150 mg, bid) or a placebo and the order of
      treatment was randomized. RESULTS: Basal LES pressure in the NIZ group (14.1
      mmHg, median) was significantly greater than that of the placebo group (8.5
      mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour
      period was significantly less than that of the placebo group (16.5/3 h) and the
      rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for
      the postprandial 3-hour period was also significantly less than that of the
      placebo group (74.4% and 2.8%, respectively). CONCLUSION: NIZ significantly
      reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during
      TLESRs.

PMID- 22374469
TI  - Carbon dioxide-induced inhibition of mechanical activity in gastrointestinal
      smooth muscle preparations isolated from the guinea-pig.
AB  - Mechanical responses of smooth muscle elicited by application of CO2-gas bubbled
      physiological salt solution (CO2-gas solution) were investigated in isolated
      stomach antrum and colon preparations of the guinea-pig. Circular smooth muscle
      preparations of both colon and stomach were spontaneously active with periodic
      generation of phasic contractions. In colonic preparations, the CO2-gas solution
      produced a biphasic response, with an initial small transient contraction
      followed by a sustained inhibition of phasic contractions. Removal of the CO2-gas
      solution allowed a slow recovery of the spontaneous contractions over a period of
      about 40 min. The recovery developed with a similar time course irrespective of
      the length of time exposed to CO2-gas solution. The inhibitory responses elicited
      by CO2-gas solution were not modulated by atropine, Nomega-nitro-L-arginine or
      neostigmine. Atropine-sensitive excitatory responses of smooth muscle elicited by
      transmural nerve stimulation or exogenously applied acetylcholine were attenuated
      or abolished in the presence of CO2-gas solution. In stomach preparations, the
      CO2-gas solution elicited a tri-phasic response, with an initial transient
      relaxation followed by a transient contraction and then a sustained inhibition of
      the rhythmic contractions. The peak amplitude of the transient contraction was
      about 2.5 times larger than the spontaneous phasic contractions. The pH of the
      CO2-gas solution was reduced to about 6. Application of pH 6 solution again
      produced a tri-phasic response, as was the case for the CO2-gas solution, however
      the amplitude of the transient contraction was only about 0.4 times that of the
      spontaneous contractions. The re-appearance of the abolished phasic contraction
      was quicker with the pH 6 solution (about 1.8 min) than it was for the CO2-gas
      solution (about 6 min). The inhibitory responses elicited by the CO2-gas solution
      could be simulated only partly by the acidified solution, and a possible
      involvement of additional factors in the inhibition elicited by CO2-gas solution
      was considered.

PMID- 22374470
TI  - Enhancing charge-storage capacity of non-volatile memory devices using template
      directed assembly of gold nanoparticles.
AB  - We demonstrate the controlled fabrication of aggregates of gold nanoparticles as
      a means of enhancing the charge-storage capacity of metal-insulator-semiconductor
      (MIS) devices by up to 300% at a low biasing voltage of +/-4 V. Aggregates of
      citrate stabilized gold nanoparticles were obtained by directed electrostatic
      self-assembly onto an underlying nanopattern of positively charged centers. The
      underlying nanopatterns consist of amine functionalized gold nanoparticle arrays
      formed using amphiphilic diblock copolymer reverse micelles as templates. The
      hierarchical self-organization leads to a twelve-fold increase in the number
      density of the gold nanoparticles and therefore significantly increases the
      charge storage centers for the MIS device. The MIS structure showed
      counterclockwise C-V hysteresis curves indicating a good memory effect. A memory
      window of 1 V was obtained at a low biasing voltage of +/-4 V. Furthermore, C-t
      measurements conducted after applying a charging bias of 4 V showed that the
      charge was retained beyond 20,000 s. The proposed strategy can be readily adapted
      for fabricating next generation solution processible non-volatile memory devices.

PMID- 22374472
TI  - Structure-dependent optical properties of single-walled silicon nanotubes.
AB  - The electron excitations of Single-Walled Silicon Nanotubes (SWSiNTs), with sp(2)
      and sp(3) hybridization, were studied using the localized-density-matrix (LDM)
      method with INDO/S parameters. Strong anisotropic characteristics of the dynamic
      polarizabilities were found for all the nanotubes. The transitional intensity
      along the tubular axis is much larger than that perpendicular to the axis for all
      the nanotubes. The optical gaps of sp(3)-hybridized infinitely-long pentagonal
      SWSiNTs are near 3.0 eV and 4.7 eV owing to sigma-sigma* transitions along the
      direction of the tubular axis. The optical gaps of sp(2)-hybridized infinitely
      long armchair SWSiNTs along the tube axis direction are about 0.7 eV and 2.4 eV
      for Si(3,3) SWSiNTs and 0.7 eV and 2.7 eV for Si(4,4) SWSiNTs. The former peak at
      0.7 eV originated from pi-pi* electron transitions and the latter peak at 2.4 eV
      or 2.7 eV originated from sigma-sigma* electron transitions. Meanwhile, the
      intensities of pi-pi* electron transitions are stronger than those of sigma
      sigma* electron transitions in SWSiNTs. The low sp(2) transition energy derived
      from the weak overlap of unpaired p(z) orbitals of silicon atoms. Moreover, the
      electronic excitations of zigzag SWSiNTs are similar to those of armchair
      structures. This indicates that sp(2)-hybridized silicon nanotubes possess much
      greater potential for application in optical fields.

PMID- 22374471
TI  - Downregulating the canonical Wnt/beta-catenin signaling pathway attenuates the
      susceptibility to autism-like phenotypes by decreasing oxidative stress.
AB  - Although a growing body of evidence supports the importance of the Wnt/beta
      catenin signaling pathway and oxidative stress in the pathogenesis of autism, it
      is unclear whether a relationship exists between the Wnt/beta-catenin pathway and
      oxidative homeostasis. The present study examines the effects of sulindac, a
      small molecule inhibitor of the Wnt/beta-catenin signaling pathway, on the
      oxidative status of rats that are prenatally exposed to valproic acid (VPA),
      which is used in an animal model of autism. Our data show that sulindac treatment
      downregulated the canonical Wnt/beta-catenin signaling pathway by enhancing the
      expression of Glycogen Synthase Kinase 3beta and attenuating the expression of
      beta-catenin in comparison to levels in VPA-treated rats. Concomitantly, a marker
      of lipid peroxidation, 4-hydroxynonenal, was reduced as well. Sulindac treatment
      ameliorated the pain threshold, repetitive/stereotypic activity, learning and
      memory abilities and behavioral abnormalities of rats in our autism model. Our
      working model suggests that the upregulation of the Wnt/beta-catenin signaling
      pathway induced by VPA administration during early pregnancy produces an
      imbalance of oxidative homeostasis that facilitates susceptibility to autism.
      This information may be instrumental in designing appropriate therapeutic
      regimens with small molecule inhibitors of the Wnt/beta-catenin pathway for the
      treatment of autism-like behavioral phenotypes.

PMID- 22374474
TI  - Controlled release of bupivacaine HCl through microchannels of biodegradable drug
      delivery device.
AB  - Local and prolonged delivery of local analgesics is much desired for post
      operative pain management. For delivery of local analgesics at a constant rate
      over couple of days, a microfluidic device comprised of a drug reservoir and
      microchannels for drug release was developed using a biodegradable polymer, 85/15
      poly(lactic-co-glycolic acid). Unlike conventional methods relying on material
      property, this device enables convenient modulation of the release speed of drugs
      by a simple change of the channel geometry such as the length and cross-sectional
      area. Bupivacaine was selected as our model local analgesic drug and its
      diffusional transport through microchannels was studied using the microfluidic
      devices. However, since the salt form of bupivacaine, bupivacaine hydrochloride,
      has pH-dependent solubility, its precipitation in microchannels had an adverse
      impact on the release performance of the microfluidic drug delivery devices.
      Thus, in this investigation, the diffusional transport and precipitation of
      bupivacaine hydrochloride in microfluidic channels were studied using in vitro
      release experiments and optical analysis. Furthermore, a concept of co-delivery
      of bupivacaine hydrochloride together with acidic additives was demonstrated to
      achieve a zero-order delivery of bupivacaine hydrochloride without the clogging
      of microchannels by its precipitation.

PMID- 22374475
TI  - Urea separation in flat-plate microchannel hemodialyzer; experiment and modeling.
AB  - Two flat-plate microchannel hemodialyzers were constructed consisting of two
      identical laminae separated by a 20[MUm] thick ultrafiltration membrane (Gambro
      AN69). Each lamina contains a parallel array of microchannels 100[MUm] deep,
      200[MUm] wide, and 5.6[cm] or 9.9[cm] in length respectively. Urea was removed
      from the aqueous stream containing 1.0[g] urea per liter de-ionized water in the
      blood side, by countercurrent contact with pure de-ionized water in the dialysate
      side of the flat-plate hemodialyzer. In all cases volumetric flow rate of water
      in the dialysate side was equal or less than the volumetric flow rate in the
      blood side, which is in large contrast to commercial applications of hollow-fiber
      hemodialyzers where dialysate flow is severalfold larger than blood flow rate. A
      three-dimensional finite volume mass transport model, built entirely from the
      first principles with no adjustable parameters, was written in FORTRAN. The
      results of the mathematical model excellently predict experimental results. The
      fractional removals of urea predicted by the model are within 2.7%-11% of
      experimentally obtained values for different blood and dialysate velocities/flow
      rates in microchannels, and for different transmembrane pressures. The overall
      mass transfer coefficient was calculated using the urea outlet concentrations
      obtained at various average velocities (1.0-5.0[cm/s]) in the blood and
      dialysate, and two nominal transmembrane pressures (?P(tm) = 0 and 10,000.[Pa]).
      Overall mass transfer coefficients obtained experimentally ranged from 0.068 to
      0.14 [cm/min]. The numerical model predicted an average overall mass transfer
      coefficient of 0.08 [cm/min]. This value is 60% higher than those found in
      commercial dialyzers (~0.05[cm/min]).

PMID- 22374476
TI  - Microfluidic assay without blocking for rapid HIV screening and confirmation.
AB  - The essential step for HIV spreading limitation is the screening tests. However,
      there are multiple disadvantages in current screening assays which need further
      confirmation test. Herein we developed a rapid HIV assay combining screening and
      confirmation test by using the microfluidic network assay. Meanwhile, the assay
      is accelerated by bypassing the step of blocking. We call this method as
      microfluidic assay without blocking (MAWB). Both the limit of detection and
      reagent incubation time of MAWB are determined by screening of one model protein
      pair: ovalbumin and its antibody. The assay time is accelerated about 25% while
      the limit of detection (LOD) is well kept. Formatting the method in for both HIV
      screening (testing 8 HIV-related samples) and confirmation (assaying 6 kinds of
      HIV antibodies of each sample) within 30 min was successful. Fast HIV screening
      and confirmation of 20 plasma samples were also demonstrated by this method. MAWB
      improved the assay speed while keeping the LOD of conventional ELISA. Meanwhile,
      both the accuracy and throughput of MAWB were well improved, which made it an
      excellent candidate for a quick HIV test for both screening and confirmation.
      Methods like this one will find wide applications in clinical diagnosis and
      biochemical analysis based on the interactions between pairs of molecules.

PMID- 22374477
TI  - Sex differences in amygdala subregions: evidence from subregional shape analysis.
AB  - Each subregion of the amygdala is characterized by a distinct cytoarchitecture
      and function. However, most previous studies on sexual dimorphism and aging have
      assessed differences in the structure of the amygdala at the level of the
      amygdala in its entirety rather than at the subregional level. Using an amygdala
      subregional shape analysis, we investigated the effects of sex, age, and the sex
      * age interaction on the subregion after controlling for intracranial volume. We
      found the main effect of age in the subregions and the effect of sex in the
      superficial nucleus, which showed that men had a larger mean radius than women.
      We also found a sex * age interaction in the centromedial nucleus, in that the
      radius of the centromedial nucleus showed a steeper decline with age in women
      compared with men. Regarding the amygdala volume as a whole, we found only an age
      effect and did not find any other significant difference between genders. The sex
      difference in the amygdala subregion and its relevance to the circulating gonadal
      hormone were discussed.

PMID- 22374479
TI  - Evolution and current challenges in the teaching of functional MRI and functional
      brain imaging.
AB  - The report of any new and successful method for studying the world triggers the
      need to train people in the use of that method. In the case of functional
      magnetic resonance imaging and its use for examining human brain function in
      vivo, expertise is required in a greater collection of domains than usual.
      Development of fMRI training programs started shortly after the announcement of
      BOLD-based fMRI in humans. These programs had a variety of durations and primary
      content areas. All programs had to deal with the challenge of bringing interested
      researchers from a wide variety of areas-many of whom had little or no
      understanding of MR physics, and/or experimental psychology, and/or the nuances
      of data analysis and modeling-to a sufficiently detailed level of knowledge that
      both the funding agencies, and the existing proprietors of the technology (often
      radiologists or MR physicists at hospitals) would take the research proposals of
      new investigators seriously. Now that fMRI-based research is well established,
      there are new educational challenges. Some have to do with the growing list of
      technologies used to study human brain function in vivo. But perhaps more
      daunting is the challenge of training consumers of the reports and claims based
      on fMRI and other brain imaging modalities. As fMRI becomes influential in
      contexts beyond the research environment-from the clinic to the courtroom to the
      legislature-training consumers of fMRI-based claims will take on increasing
      importance, and represents its own unique challenges for education.

PMID- 22374478
TI  - Bridging the hemispheres in meditation: thicker callosal regions and enhanced
      fractional anisotropy (FA) in long-term practitioners.
AB  - Recent findings suggest a close link between long-term meditation practices and
      the structure of the corpus callosum. Prior analyses, however, have focused on
      estimating mean fractional anisotropy (FA) within two large pre-defined callosal
      tracts only. Additional effects might exist in other, non-explored callosal
      regions and/or with respect to callosal attributes not captured by estimates of
      FA. To further explore callosal features in the framework of meditation, we
      analyzed 30 meditators and 30 controls, carefully matched for sex, age, and
      handedness. We applied a multimodal imaging approach using diffusion tensor
      imaging (DTI) in combination with structural magnetic resonance imaging (MRI).
      Callosal measures of tract-specific FA were complemented with other global
      (segment-specific) estimates as well as extremely local (point-wise) measures of
      callosal micro- and macro-structure. Callosal measures were larger in long-term
      meditators compared to controls, particularly in anterior callosal sections.
      However, differences achieved significance only when increasing the regional
      sensitivity of the measurement (i.e., using point-wise measures versus segment
      specific measures) and were more prominent for microscopic than macroscopic
      characteristics (i.e., callosal FA versus callosal thickness). Thicker callosal
      regions and enhanced FA in meditators might indicate greater connectivity,
      possibly reflecting increased hemispheric integration during cerebral processes
      involving (pre)frontal regions. Such a brain organization might be linked to
      achieving characteristic mental states and skills as associated with meditation,
      though this hypothesis requires behavioral confirmation. Moreover, longitudinal
      studies are required to address whether the observed callosal effects are induced
      by meditation or constitute an innate prerequisite for the start or successful
      continuation of meditation.

PMID- 22374480
TI  - The neural mechanisms of affect infusion in social economic decision-making: a
      mediating role of the anterior insula.
AB  - Though emotions have been shown to have sometimes dramatic effects on decision
      making, the neural mechanisms mediating these biases are relatively unexplored.
      Here, we investigated how incidental affect (i.e. emotional states unrelated to
      the decision at hand) may influence decisions, and how these biases are
      implemented in the brain. Nineteen adult participants made decisions which
      involved accepting or rejecting monetary offers from others in an Ultimatum Game
      while undergoing functional magnetic resonance imaging (fMRI). Prior to each set
      of decisions, participants watched a short video clip aimed at inducing either a
      sad or neutral emotional state. Results demonstrated that, as expected, sad
      participants rejected more unfair offers than those in the neutral condition.
      Neuroimaging analyses revealed that receiving unfair offers while in a sad mood
      elicited activity in brain areas related to aversive emotional states and
      somatosensory integration (anterior insula) and to cognitive conflict (anterior
      cingulate cortex). Sad participants also showed a diminished sensitivity in
      neural regions associated with reward processing (ventral striatum). Importantly,
      insular activation uniquely mediated the relationship between sadness and
      decision bias. This study is the first to reveal how subtle mood states can be
      integrated at the neural level to influence decision-making.

PMID- 22374483
TI  - Preserving tradition and embracing change.

PMID- 22374481
TI  - The neuromagnetic response to spoken sentences: co-modulation of theta band
      amplitude and phase.
AB  - Speech elicits a phase-locked response in the auditory cortex that is dominated
      by theta (3-7 Hz) frequencies when observed via magnetoencephalography (MEG).
      This phase-locked response is potentially explained as new phase-locked activity
      superimposed on the ongoing theta oscillation or, alternatively, as phase
      resetting of the ongoing oscillation. The conventional method used to distinguish
      between the two hypotheses is the comparison of post- to prestimulus amplitude
      for the phase-locked frequency across a set of trials. In theory, increased
      amplitude indicates the presence of additive activity, while unchanged amplitude
      points to phase-resetting. However, this interpretation may not be valid if the
      amplitude of ongoing background activity also changes following the stimulus. In
      this study, we employ a new approach that circumvents this problem. Specifically,
      we utilize a fine-grained time-frequency analysis of MEG channel data to examine
      the co-modulation of amplitude change and phase coherence in the post-stimulus
      theta-band response. If the phase-locked response is attributable solely to phase
      resetting of the ongoing theta oscillation, then amplitude and phase coherence
      should be uncorrelated. In contrast, additive activity should produce a positive
      correlation. We find significant positive correlation not only during the onset
      response but also throughout the response period. In fact, transient increases in
      phase coherence are accompanied by transient increases in amplitude in accordance
      with a "signal plus background" model of the evoked response. The results support
      the hypothesis that the theta-band phase-locked response to attended speech
      observed using MEG is dominated by additive phase-locked activity.

PMID- 22374482
TI  - Cancerous HLA class I expression and regulatory T cell infiltration in gastric
      cancer.
AB  - BACKGROUND: Since antitumor immune reactions between tumors and intratumoral
      immunocytes have been verified in several human tumors, immunological therapeutic
      strategies must be considered to obtain the proper efficacy of tumor shrinkage
      under these conditions. Human leukocyte antigen (HLA) class I expression in
      cancer cells and degree of infiltration of regulatory T cells (Tregs) in the
      stroma have been regarded as important markers of antitumor immune reactions in
      the context of independent immunological mechanisms. In the current study, we
      investigated HLA class I expression and Treg cells infiltration in gastric cancer
      and discussed the clinical implications of this combinatory analysis in gastric
      cancer. PATIENTS AND METHODS: A total of 141 gastric cancer patients who received
      R0 gastrectomy at Kagoshima University Hospital were studied.
      Immunohistochemically, in 141 gastric cancer patients, HLA class I expression and
      Treg cell infiltration in cancerous tissue were evaluated using HLA class I (EMR8
      5) and forkhead box p3 (FOXP3) monoclonal antibodies. The correlation between
      clinical factors and tumor-infiltrating Treg cells was analyzed. RESULTS: HLA
      class I expression was positively associated with depth of tumor invasion (P <
      0.05). Infiltration of Foxp3-positive cells did not correlate with any
      clinicopathological markers. HLA class I expression had no association with Treg
      cell infiltration (r = 0.04). A better postoperative outcome was associated with
      fewer numbers of Treg infiltration (P = 0.034). A combination of HLA and Treg
      analysis may lead to a more accurate prediction of postoperative outcome (P =
      0.02). CONCLUSIONS: Two different antitumor immunological markers, Treg
      infiltration and HLA class I expression, affected clinicopathological factors in
      gastric cancer by different mechanisms. Thus, an immunological combination of HLA
      class I expression and Treg cell infiltration may more accurately predict
      postoperative outcome. Immunological balance needs to be restored after
      evaluation of each immunological deficit in gastric cancer.

PMID- 22374484
TI  - Guest editorial about nurses' titles garners appreciation.

PMID- 22374485
TI  - Lifelong learning for professional oncology nurses.

PMID- 22374487
TI  - Evaluation of outpatient oncology services using lean methodology.

PMID- 22374488
TI  - Heart failure in a breast cancer survivor.

PMID- 22374489
TI  - Gastrointestinal symptom representation in cancer symptom clusters: a synthesis
      of the literature.
AB  - PURPOSE/OBJECTIVES: To review how gastrointestinal (GI)symptoms are represented
      within symptom clusters in patients with cancer receiving chemotherapy. DATA
      SOURCES: MedLINE, PsycINFO, and CINAHL. DATA SYNTHESIS: Forty-two symptom
      clusters containing a GI component emerged. Only four clusters were replicated in
      different samples; 38 were unique clusters. Thirteen different symptom
      measurement tools were used across the studies. Nineteen different GI symptoms
      were measured; however, many chemotherapy- or cancer-related GI symptoms known to
      be present in this population were missing or underrepresented. Twenty-one of the
      studies reviewed identified a symptom cluster that was primarily (50% or greater)
      composed of GI symptoms. CONCLUSIONS: GI symptoms are prevalent in symptom
      clusters, but those clusters often are inconsistent. One explanation for this
      finding may be that current symptom measurement tools do not fully address GI
      symptoms commonly experienced by patients receiving chemotherapy. IMPLICATIONS
      FOR NURSING: Future research should focus on using a comprehensive symptom
      assessment tool in a homogenous sample of participants who are receiving
      chemotherapy. Improved measurement of GI symptoms will advance symptom cluster
      research, which could impact assessment of chemotherapy-related symptoms and
      development of interventions for symptom clusters.

PMID- 22374490
TI  - Practice environments of nurses employed in ambulatory oncology settings: measure
      refinement.
AB  - PURPOSE/OBJECTIVES: To examine the reliability and validity of modified items
      from the Practice Environment Scale of the Nursing Work Index (PES-NWI) for use
      in the understudied ambulatory oncology setting. DESIGN: Cross-sectional mailed
      survey using a modified Dillman method. SETTING: Southeastern United States.
      SAMPLE: Population-based statewide sample of 1,339 oncology nurses who reported
      employment outside of hospital inpatient units. METHODS: After examining for
      nonresponse bias, confirmatory factor analysis using structural equation modeling
      and Cronbach coefficient alphas were employed to examine construct validity and
      internal consistency, respectively. After calculating revised subscale means for
      each nurse, the researchers used t tests to compare subscale means between nurses
      who reported their practice environment as favorable versus those who reported it
      as mixed or unfavorable. MAIN RESEARCH VARIABLES: Reliability and validity of
      items on the adapted version of the PES-NWI. FINDINGS: Despite a response rate of
      31%, no differences in demographic characteristics were observed between the
      analytic sample and nonresponders. After reducing the number of items to 23,
      acceptable model fit was achieved with a comparative fit index of 0.95 and a root
      mean square error of approximation of 0.057. All five existing PES-NWI subscales,
      plus the new medical assistant support subscale, were significantly higher for
      nurses who reported favorable practice environments versus those who reported
      mixed or unfavorable environments. CONCLUSIONS: A revised set of items derived
      from the PES-NWI has acceptable reliability and validity to measure the quality
      of nursing practice environments in ambulatory oncology settings. Medical
      assistant support is a new contribution to the item pool. IMPLICATIONS FOR
      NURSING: Additional testing of this revised measure in diverse samples of nurses,
      including studies that correlate with patient outcomes, is a necessary next step.

PMID- 22374491
TI  - A brief intervention to minimize psychosexual morbidity in dyads coping with
      breast cancer.
AB  - PURPOSE/OBJECTIVES: To develop and evaluate the feasibility of a brief
      intervention to attenuate the incidence of psychosexual morbidity within the dyad
      secondary to the diagnosis and treatment of breast cancer. DESIGN:
      Quasiexperimental, including intervention and treatment-as-usual comparison
      groups. SETTING: Breast clinic of a comprehensive cancer center in the Midwest
      United States. SAMPLE: 65 recently diagnosed breast cancer survivors who were pre
      or perimenopausal and aged 20-55 years, and their partners. METHODS: Three
      intervention sessions were delivered based on a manual developed for the study.
      Twenty-five dyads received treatment as usual, 26 dyads received a face-to-face
      intervention, and 14 dyads received the same intervention by telephone.
      Questionnaires were completed at baseline, following completion of the
      intervention, six months postintervention, and from the comparison group at
      equivalent data points. MAIN RESEARCH VARIABLES: Intimacy, sexual functioning,
      and dyadic adjustment. FINDINGS: About 98% of dyads completed all intervention
      sessions, with an equal level of satisfaction among those in the telephone and
      face-to-face groups. Interesting trends in differences between the intervention
      and comparison groups on the relationship variables of intimacy, sexual
      functioning, and dyadic adjustment were obtained; however, given the sample size,
      power was not sufficient to reach statistical significance. CONCLUSIONS: The
      intervention is feasible and acceptable for dyads comfortable discussing their
      relationship. Intervention by telephone was demonstrated to be as effective as
      the face-to-face mode of delivery. IMPLICATIONS FOR NURSING: Nurses need to
      provide an opportunity for women to discuss problems they are experiencing
      relative to sexuality, intimacy, and body image.

PMID- 22374492
TI  - Body composition after bone marrow transplantation in childhood.
AB  - PURPOSE/OBJECTIVES: To describe the body composition and fat distribution of
      childhood bone marrow transplantation (BMT) survivors at least one year post
      transplantation and examine the ability of the Centers for Disease Control and
      Prevention criteria to identify survivors with elevated body fat percentage.
      DESIGN: Cross-sectional, descriptive. SETTING: Pediatric oncology program at a
      National Cancer Institute-designated comprehensive cancer center. SAMPLE: 48
      childhood BMT survivors (27 males and 21 females). METHODS: Measurements included
      dual-energy x-ray absorptiometry scan, height, weight, and physical activity.
      Descriptive statistics were reported and mixed-model linear regression models
      were used to describe findings and associations. MAIN RESEARCH VARIABLES: Total
      body fat percentage and central obesity (defined as a ratio of central to
      peripheral fat of 1 or greater). FINDINGS: Fifty-four percent of survivors had
      body fat percentages that exceeded recommendations for healthy body composition
      and 31% qualified as having central obesity. Previous treatment with total body
      irradiation was associated with higher body fat percentage and central obesity,
      and graft-versus-host disease was associated with lower body fat percentage. The
      body mass index (BMI) criteria did not correctly identify the BMT survivors who
      had elevated body fat percentage. CONCLUSIONS: Survivors of childhood BMT are at
      risk for obesity and central obesity that is not readily identified with standard
      BMI criteria. IMPLICATIONS FOR NURSING: Nurses caring for BMT survivors should
      include evaluation of general and central obesity in their assessments. Patient
      education materials and resources for healthy weight and muscle building should
      be made available to survivors. Research is needed to develop appropriate
      interventions.

PMID- 22374493
TI  - Bridging the gap: a descriptive study of knowledge and skill needs in the first
      year of oncology nurse practitioner practice.
AB  - PURPOSE/OBJECTIVES: To identify the knowledge and skill needs of oncology nurse
      practitioners (ONPs) as they enter cancer care practice, and to identify
      necessary educational resources. DESIGN: Cross-sectional, descriptive. SETTING: A
      national e-mail survey. SAMPLE: 610 self-described ONPs from the Oncology Nursing
      Society's database. METHODS: The project team developed a 28-item electronic
      survey. The survey was randomly distributed via e-mail. MAIN RESEARCH VARIABLES:
      ONPs' feelings of preparedness in the first year of ONP practice. FINDINGS: In
      the first year of practice, 90% of ONPs rated themselves as prepared or very
      prepared in obtaining patient history, performing physical examination, and
      documenting findings. ONPs rated themselves as not at all or somewhat prepared in
      clinical issues of chemotherapy/biotherapy competency (n = 81, 78%), recognizing
      and managing oncologic emergencies, (n = 77, 70%), and recognizing and managing
      drug toxicities (n = 63, 61%). The primary source of oncology education for ONPs
      new to practice was almost exclusively the collaborating or supervising physician
      (n = 84, 81%). CONCLUSIONS: Specific knowledge and skills, such as information
      about chemotherapy, oncologic emergencies, and side effects of therapy, are
      needed before an ONP enters a cancer care practice. IMPLICATIONS FOR NURSING:
      Cancer-specific education should be made available to new ONPs as they begin
      independent practice.

PMID- 22374494
TI  - Children's coping strategies for chemotherapy-induced nausea and vomiting.
AB  - PURPOSE/OBJECTIVES: To identify anticipatory, acute, and delayed chemotherapy
      induced nausea and vomiting (CINV) frequency and coping strategies used among
      pediatric patients with cancer. DESIGN: Prospective, cohort design. SETTING: A
      pediatric teaching hospital in the southern United States. SAMPLE: A convenience
      sample of 40 children aged 7-12 years scheduled to receive either moderately
      emetic chemotherapy or highly emetic chemotherapy for cancer treatment. METHODS:
      Children completed the Adapted Rhodes Index of Nausea and Vomiting for Pediatrics
      and the Kidcope-Younger Version. MAIN RESEARCH VARIABLES: CINV and coping
      strategies. FINDINGS: CINV occurred during the anticipatory, acute, and delayed
      times, with the highest frequency occurring during the delayed time. The most
      frequently used coping strategies were distraction and wishful thinking, whereas
      the most effective strategies were social support and distraction. No
      statistically significant differences were observed in the frequency or efficacy
      of coping strategies over time. CONCLUSIONS: CINV occurs throughout chemotherapy
      treatment. The most efficacious coping strategies included active and passive
      coping, with active coping strategies being more effective. IMPLICATIONS FOR
      NURSING: Nurses should recognize that CINV occurs at all points of chemotherapy
      treatment. Nurses can assist children in developing active coping strategies to
      manage their CINV.

PMID- 22374495
TI  - Long-term breast cancer survivors' perceptions of support from female partners:
      an exploratory study.
AB  - PURPOSE/OBJECTIVES: To describe the social support experiences of long-term
      breast cancer survivors who have female partners, from the perspective of
      survivors. RESEARCH APPROACH: Descriptive study using qualitative methods.
      SETTING: United States. PARTICIPANTS: A purposive convenience sample of 15
      partnered sexual minority women (SMW) (e.g., women with female partners)
      diagnosed with nonmetastatic breast cancer from 2000-2005. METHODOLOGIC APPROACH:
      One-on-one interviews were conducted by telephone. Interviews were semistructured
      through the use of an interview guide. Transcribed data were coded and analyzed
      to identify emergent themes. MAIN RESEARCH VARIABLES: Perceptions of support and
      broad aspects of the intimate partner relationship that may critically impact the
      psychological well-being of SMW following breast cancer. FINDINGS: Six salient
      themes describe SMW survivors' perceptions of support: (a) female partners are
      the singular source of survivors' most valuable support; partners support
      survivors by (b) discussing survivors' health and distress, which survivors
      associate with (c) perceived partner distress, and (d) managing the home and
      caretaking, which survivors associate with (e) perceived partner burden; and
      partners support survivors by (f) sharing in a life beyond cancer. CONCLUSIONS:
      Female partners play a central and comprehensive support role as well as
      experience ongoing stress and burden related to survivors' cancer.
      INTERPRETATION: Future research and direct investigation may inform healthcare
      providers about caring for SMW and their families following breast cancer.

PMID- 22374498
TI  - Getting to the point: what women newly diagnosed with breast cancer want to know
      about treatment-focused genetic testing.
AB  - PURPOSE/OBJECTIVES: To identify young women's information preferences regarding
      treatment-focused genetic testing (TFGT) and to develop and evaluate a novel
      educational resource. RESEARCH APPROACH: Qualitative interview study and pilot
      testing of a novel resource. SETTING: Two familial cancer services and one
      outpatient oncology clinic in Sydney and Melbourne, Australia. PARTICIPANTS: 26
      women with breast cancer aged 50 years and younger who either previously had TFGT
      (n = 14) or had a diagnosis of breast cancer within the previous 6-12 months.
      METHODOLOGIC APPROACH: Participants were asked about their views of TFGT in
      semistructured interviews. A brief pamphlet on TFGT then was developed and pilot
      tested with 17 of the 26 women. MAIN RESEARCH VARIABLES: Women's attitudes and
      preferences with regard to timing, mode of delivery, and amount and format of
      information regarding TFGT were explored. FINDINGS: Most women wanted to be
      informed about TFGT at or around the time of their cancer diagnosis via a face-to
      face consultation. No clear preference existed for which type of healthcare
      professional should provide information on TFGT. Brief written information about
      TFGT was viewed as important supporting material. The educational resource
      developed was well received. CONCLUSIONS: The potential for more widespread TFGT
      in the future indicates a need for patient educational materials that enable
      women to make informed choices about TFGT. This pilot study has provided timely
      initial evidence on the efficacy of a brief written resource in preparing women
      for decision making about TFGT. INTERPRETATION: The resource developed in this
      study will assist oncology nurses to make important genetic risk information
      available to women newly diagnosed with breast cancer at a stressful time.

PMID- 22374499
TI  - Impact of patient smoking behavior on empathic helping by family caregivers in
      lung cancer.
AB  - PURPOSE/OBJECTIVES: To test the impact of patient smoking behavior on family
      caregiver judgments of responsibility, emotions, empathic responses, and helping
      behavior. DESIGN: Structural equation modeling. SETTING: Five oncology outpatient
      settings in Canada. SAMPLE: 304 dyads consisting of patients with lung cancer and
      their primary caregivers. METHODS: Self-report questionnaires, abstracted medical
      record data, confirmatory factor analysis, and structural equation modeling. MAIN
      RESEARCH VARIABLES: Smoking history, judgments of responsibility for controlling
      the disease, anger, pride, empathic responses, and helping behaviors. FINDINGS:
      The impact of patient smoking behavior on caregiver help was mediated by
      caregiver judgments of responsibility, affective reactions of anger and pride,
      and empathic responses by caregivers. CONCLUSIONS: When patients continued to
      engage in smoking behavior, despite a diagnosis of lung cancer, caregivers tended
      to ascribe more responsibility and feel more anger and less pride in the
      patients' efforts to manage the disease, therefore placing caregivers at risk for
      less empathy and helping behavior. IMPLICATIONS FOR NURSING: Caregiver blame and
      anger must be assessed, particularly when the patient with lung cancer continues
      to smoke. If caregiver judgments of blame and anger are evident, then an
      attribution approach is indicated involving a dialogue between the caregiver and
      the patient, with the aim of enhancing the caregiver's understanding of how
      negative attributions and linked emotions impact his or her ability to engage in
      empathic helping behaviors.

PMID- 22374501
TI  - Health-promotion behaviors and psychological distress in cancer survivors.
AB  - PURPOSE/OBJECTIVES: To determine whether cancer survivors engage in health
      promotion behaviors, to evaluate the extent of their experience of psychological
      distress, and to investigate the relationship between the practice of health
      promotion behaviors and psychological distress. DESIGN: Cross-sectional secondary
      data analysis. SETTING: A national, face-to-face interview conducted by personnel
      of the U.S. Census Bureau using a random sampling of American adults. SAMPLE:
      1,784 survey respondents who reported a previous cancer diagnosis. METHODS: Data
      from the 2009 National Health Interview Survey were used to examine the
      prevalence of smoking, physical inactivity, alcohol use, and reports of
      psychosocial distress. Interviews pertained to the amount and distribution of
      illness, its effects in terms of disability and chronic impairments, and the
      kinds of health services people receive. MAIN RESEARCH VARIABLES: Age, current
      smoking prevalence, alcohol consumption, physical activity, and the experience of
      feeling hopelessness, sadness, and anxiety. FINDINGS: Cancer survivors continue
      to smoke at a rate similar to the national average. Overall, most respondents
      reported no symptoms of psychological distress. However, age appears to play a
      major role, showing significant differences in the prevalence of current smoking,
      participation in physical activity, alcohol use, and reported level of distress.
      CONCLUSIONS: This study provides estimates of the prevalence of health-promotion
      behaviors and experience of psychological distress among American cancer
      survivors. The results reveal opportunities for interventions among cancer
      survivors. IMPLICATIONS FOR NURSING: Nurses should be proactive in providing
      guidance to survivors regarding the adoption of healthy lifestyle behaviors.
      Those who encounter younger cancer survivors need to be alert to the higher
      potential for distress in that population, perform appropriate screenings, and be
      prepared to offer guidance, supportive care, and referrals for psychological care
      if needed.

PMID- 22374502
TI  - Pilot study of a survey to identify the prevalence of and risk factors for
      chronic neuropathic pain following breast cancer surgery.
AB  - PURPOSE/OBJECTIVES: To provide a preliminary determination of the prevalence rate
      of women who suffer from neuropathic pain post breast surgery (PPBS) and explore
      potential risk factors associated with its development. DESIGN: Prospective,
      quantitative, longitudinal survey. SETTING: Breast health clinic in western
      Canada. SAMPLE: A convenience sample of 17 women undergoing breast cancer
      surgery. METHODS: The Brief Pain Inventory was administered before surgery and 2
      days, 10 days, and 3 months postsurgery. Demographic data also were collected
      preoperatively. Analysis included determining prevalence of PPBS; descriptive
      analyses on age, gender, and body mass index (BMI); presence of acute
      postoperative pain; type of surgery; and two-tailed t tests on age and BMI. MAIN
      RESEARCH VARIABLES: The symptom experience of chronic PPBS. FINDINGS: Twenty
      three percent of the sample developed PPBS. Younger age (50 years or younger),
      more invasive surgery, acute postoperative pain, and less analgesic use during
      the acute postoperative period were factors associated with the development of
      PPBS. CONCLUSIONS: Additional research is required to confirm the significance of
      these potential risk factors in the development of PPBS. IMPLICATIONS FOR
      NURSING: Nurses are ideally situated to identify early signs of PPBS. In
      addition, nurses play a key role in the education of patients and healthcare
      professionals and can facilitate increased awareness about the possibility of
      developing PPBS, enabling earlier and more effective treatment of PPBS.

PMID- 22374500
TI  - Predictors of quality of life for long-term cancer survivors with preexisting
      disabling conditions.
AB  - PURPOSE/OBJECTIVES: To explore whether measures of resources, barriers, and
      health-promoting behaviors would add significantly to the prediction of health
      related quality of life among survivors with disabilities that occurred prior to
      their cancer diagnosis once contextual factors were controlled for. DESIGN: A
      descriptive correlational study. SETTING: Adult cancer survivors with preexisting
      disabling conditions who had completed active treatment were recruited from
      throughout the United States. SAMPLE: Most of the 145 respondents were breast
      cancer survivors with preexisting neuromuscular conditions such as polio and
      multiple sclerosis. The average time since cancer diagnosis was nine years.
      METHODS: Respondents completed a mailed survey. MAIN RESEARCH VARIABLES: Health
      promoting behaviors, self-efficacy, barriers to health promotion, social support,
      functional limitations, cancer-related variables, depression, and quality of
      life. FINDINGS: The sample reported poorer physical well-being than other cancer
      survivors without preexisting disabling conditions. Health-promoting behaviors
      and psychosocial factors, such as depressive symptoms and self-efficacy, added
      significantly to the prediction of physical, social, emotional, and functional
      components of health-related quality of life after contextual factors entered the
      equations. CONCLUSIONS: The findings underscore the importance of providing this
      population with the means to promote their health to the greatest extent
      possible, given the multiple threats to their health status. IMPLICATIONS FOR
      NURSING: Nurses may be able to help survivors with preexisting disabling
      conditions reduce the negative influence of poorer health status and functional
      limitations on quality of life by providing interventions that reduce depression
      and build perceived ability to engage in health-promoting behaviors.

PMID- 22374503
TI  - Signs of aging or the vague symptoms of ovarian cancer?
AB  - PURPOSE/OBJECTIVES: To explore the feelings that occurred at the same time as the
      vague physical symptoms of ovarian cancer. RESEARCH APPROACH: Qualitative,
      descriptive methodology. SETTING: University cancer institute in southeastern
      United States. PARTICIPANTS: 24 women (ages 39-78) diagnosed with ovarian cancer.
      Most were Caucasian, were diagnosed at stage II-III, had a college-level
      education, and had health insurance. Eighty-three percent did not know the signs
      and symptoms of ovarian cancer prior to diagnosis, and 91% had no family history
      of the cancer. METHODOLOGIC APPROACH: SPSS (version 18.0) was used to summarize
      the demographic characteristics and qualitative descriptive content analysis to
      identify and summarize themes in the narrative data. FINDINGS: Two themes were
      noted in the handwritten answers provided by the women: (a) "thought symptoms
      were aging" and (b) "felt or knew something was not right." CONCLUSIONS: Findings
      demonstrate and reinforce that a need exists for education regarding signs and
      symptoms of ovarian cancer among the general population as well as the common
      providers of women's health care. INTERPRETATION: Education campaigns on signs
      and symptoms of ovarian cancer and normal aging are necessary so women are
      empowered with knowledge and healthcare providers can suspect and evaluate the
      symptoms.

PMID- 22374504
TI  - InterACTIV: an exploratory study of the use of a game console to promote physical
      activation of hospitalized adult patients with cancer.
AB  - PURPOSE/OBJECTIVES: To explore the application of the Nintendo Wii game console
      to motivate hospitalized adult patients with cancer to be physically active
      during treatment periods. DESIGN: An exploratory study with a mixed-method
      approach, including descriptive statistics and Mayring's qualitative data
      evaluation method. SETTING: The Department of Radiation Oncology at the
      University Hospital in Halle (Saale) in Germany. SAMPLE: Convenience sample of 7
      adult inpatients. METHODS: All patients received physical training for five days
      for 30 minutes per day with Nintendo Wii. After the last training session,
      patients were interviewed using a semistructured guideline. MAIN RESEARCH
      VARIABLES: Applicability of a motion-activated game console during inpatient
      treatment periods, patients' distraction from the hospital environment. FINDINGS:
      In general, the use of a motion-activated game console in a hospital environment
      was evaluated positively. Participants showed a high degree of acceptance using
      this kind of physical activity. Because of the Nintendo Wii, the majority of
      individuals felt stimulated to become physically active during hospitalization.
      In addition, all patients lost time awareness and felt distracted from the daily
      hospital routine. A majority of the patients reported an improved mood state from
      the game sessions. CONCLUSIONS: The results indicate that a motion-activated game
      console could be useful to motivate adult patients with cancer to be physically
      active during hospitalization. IMPLICATIONS FOR NURSING: Nurses can recommend the
      use of game consoles such as the Nintendo Wii for physical exercise; in addition,
      the motivational effects of playing motion-activated game consoles might be
      particularly helpful for patients with cancer-related fatigue to overcome
      barriers and begin exercise.

PMID- 22374505
TI  - Perceived discrimination and ethnic identity among breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To examine ethnic identity and socio-demographic factors in
      minority patients' perceptions of healthcare discrimination in breast cancer
      care. DESIGN: Mixed methods. SETTING: Participants' homes in the metropolitan
      areas of Phoenix and Tucson, AZ. SAMPLE: 39 women treated for breast cancer in
      the past six years: 15 monolingual Spanish-speaking Latinas, 15 English-speaking
      Latinas, and 9 African Americans. METHODS: Two questionnaires were administered.
      Individual interviews with participants were conducted by nurse researchers.
      Quantitative, qualitative, and matrix analytic methods were used. MAIN RESEARCH
      VARIABLES: Ethnic identity and perceptions of discrimination. FINDINGS: Eighteen
      women (46%) believed race and spoken language affected the quality of health
      care. Perceived dis-respect from providers was attributed to participant's skin
      color, income level, citizenship status, and ability to speak English.
      Discrimination was more likely to be described in a primary care context, rather
      than cancer care. Ethnic identity and early-stage breast cancer diagnosis were
      the only study variables significantly associated with perceived healthcare
      discrimination. CONCLUSIONS: This article describes the first investigation
      examining ethnic identity and perceived discrimination in cancer care delivery.
      Replication of this study with larger samples is needed to better understand the
      role of ethnic identity and cancer stage in perceptions of cancer care delivery.
      IMPLICATIONS FOR NURSING: Identification of ethnic-specific factors that
      influence patient's perspectives and healthcare needs will facilitate development
      of more effective strategies for the delivery of cross-cultural patient-centered
      cancer care.

PMID- 22374507
TI  - On the validation of magnetic resonance velocimetry in single-phase turbulent
      pipe flows.
AB  - A nuclear magnetic resonance imaging technique is used to measure velocity
      distributions in turbulent pipe flows up to Re=24580. While turbulent intensity
      is usually determined from signal attenuation, we deduce turbulent intensity from
      velocity distribution with no need to suppose a gaussian distribution for
      velocity fluctuations. Skewness and flatness measurements are also presented in
      this paper. Comparison with DNS show good agreement and we show that NMR data is
      sufficently accurate to provide turbulent viscosity profile. The low field system
      used in this study allow the suppression of susceptibility artifacts and thus
      open its use for studying two-phase flows. We postulate that the method used here
      could be applied to two-phase flows and would thus provide valuable information
      on turbulent viscosity models.

PMID- 22374509
TI  - Hepatic S4a + S5 and bile duct resection for gallbladder carcinoma.
AB  - In the surgical treatment of gallbladder cancer, segment 4a + 5 hepatic resection
      and bile duct resection is usually recommended for T2 and/or T3 gallbladder
      cancer involving hepatic parenchyma without hepatic biliary confluence. This
      procedure does not affect liver function excessively, provided there is correct
      identification of hepatic S4a and S5, the most important aspect of this
      procedure. In this paper, the technique of hepatic S4a + 5 and bile duct
      resection is described in detail. This surgical procedure could be a useful
      option for the surgical treatment of the hepatobiliary pancreatic malignancies.
      Surgeons should therefore master the surgical techniques for this procedure.

PMID- 22374510
TI  - Human placentation from nidation to 5 weeks of gestation. Part I: What do we know
      about formative placental development following implantation?
AB  - The implantation of the blastocyst and early development of the placenta are
      crucial for the success of implantation and pregnancy. However, the formative
      stages of human placental development are largely unknown because of their
      existence in a 'black box' where access to samples is extremely limited for
      ethical reasons. In this review we discuss our current knowledge of early
      placental formation from the time of implantation at 3 weeks of gestation to
      approximately 5-6 weeks of gestation, encompassing both the significant
      anatomical findings derived from the unique specimens obtained in the mid-20th
      century and the renewed study of this period over the past 10 years as novel
      models of implantation have been developed.

PMID- 22374508
TI  - A clinically relevant bi-cellular murine mammary tumor model as a useful tool for
      evaluating the effect of retinoic acid signaling on tumor progression.
AB  - BACKGROUND: The effect of retinoic acid (RA) on breast cancer progression is
      controversial. Our objective was to obtain information about breast cancer
      progression, taking advantage of the ER-negative murine mammary adenocarcinoma
      model LM38 (LM38-LP constituted by luminal (LEP) and myoepithelial-like cells
      (MEP), LM38-HP mainly composed of spindle-shaped epithelial cells, and LM38-D2
      containing only large myoepithelial cells), and to validate the role of the
      retinoic acid receptors (RARs) in each cell-type compartment. MATERIALS AND
      METHODS: We studied the expression and functionality of the RARs in LM38 cell
      lines. We analyzed cell growth and cell cycle distribution, apoptosis, the
      activity of proteases, motility properties, and expression of the molecules
      involved in these pathways. We also evaluated tumor growth and dissemination in
      vivo under retinoid treatment. RESULTS: LM38 cell lines expressed most retinoic
      receptor isotypes that were functional. However, only the bi-cellular LM38-LP
      cells responded to retinoids by increasing RARbeta2 and CRBP1 expression. The
      growth of LM38 cell sublines was inhibited by retinoids, first by inducing arrest
      in MEP cells, then apoptosis in LEP cells. Retinoids induced inhibitory effects
      on motility, invasiveness, and activity of proteolytic enzymes, mainly in the
      LM38-LP cell line. In in-vivo assays with the LM38-LP cell line, RA treatment
      impaired both primary tumor growth and lung metastases dissemination. CONCLUSION:
      These in-vivo and in-vitro results show that to achieve maximum effects of RA on
      tumor progression both the LEP and MEP cell compartments have to be present,
      suggesting that the interaction between the LEP and MEP cells is crucial to full
      activation of the RARs.

PMID- 22374506
TI  - In utero exposure to benzo(a)pyrene predisposes offspring to cardiovascular
      dysfunction in later-life.
AB  - In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic
      hydrocarbon, is thought to dysregulate cardiovascular development. To investigate
      the effects of in utero B(a)P exposure on cardiovascular development, timed
      pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300,
      600 and 1200 MUg/kg/BW) by oral gavage on embryonic (E) days E14 (the
      metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no
      significant effects of in utero exposure to B(a)P on the number of pups born per
      litter or in pre-weaning growth curves. Pre-weaning profiles for B(a)P metabolite
      generation from cardiovascular tissue were shown to be dose-dependent and
      elimination of these metabolites was shown to be time-dependent in exposed
      offspring. Systolic blood pressure on postnatal day P53 in the middle and high
      exposure groups of offspring were significantly elevated as compared to controls.
      Microarray and quantitative real-time PCR results were directly relevant to a
      biological process pathway in animal models for "regulation of blood pressure".
      Microarray and quantitative real-time PCR analysis revealed upregulation of mRNA
      expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric
      oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene
      set enrichment analysis subsequently identified potential signaling mechanisms
      and molecular pathways that might explain the elevated systolic blood pressures
      observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure
      to B(a)P predispose offspring to functional deficits in cardiovascular
      development that may contribute to cardiovascular dysfunction in later life.

PMID- 22374511
TI  - Meta-analysis of data from human ex vivo placental perfusion studies on genotoxic
      and immunotoxic agents within the integrated European project NewGeneris.
AB  - In the E.U. integrated project NewGeneris, we studied placental transport of
      thirteen immunotoxic and genotoxic agents in three ex vivo placental perfusion
      laboratories. In the present publication, all placental perfusion data have been
      re-analyzed and normalized to make them directly comparable and rankable.
      Antipyrine transfer data differed significantly between the studies and
      laboratories, and therefore normalization of data was necessary. An antipyrine
      normalization factor was introduced making the variance significantly smaller
      within and between the studies using the same compound but performed in different
      laboratories. Non-normalized (regular) and normalized data showed a good
      correlation. The compounds were ranked according to their transplacental transfer
      rate using either antipyrine normalized AUC120 or transfer index (TI120(%)).
      Normalization generated a division of compounds in slow, medium and high transfer
      rate groups. The transfer rate differed slightly depending on the parameter used.
      However, compounds with passage similar to antipyrine which goes through the
      placenta by passive diffusion, and good recovery in media (no accumulation in the
      tissue or adherence to equipment) were highly ranked no matter which parameter
      was used. Antipyrine normalization resulted in the following ranking order of
      compounds according to AUC(120NORM) values: NDMA >= EtOH >= BPA >= IQ >=AA >= GA
      >= PCB180 >= PhIP >= AFB1 > DON >= BP >= PCB52 >= TCDD. As the variance in all
      parameters within a study decreased after antipyrine normalization, we conclude
      that this normalization approach at least partially corrects the bias caused by
      the small methodological differences between studies.

PMID- 22374512
TI  - The effect of nurse practitioner practice in home care on emergency department
      visits for homebound older adult patients: an exploratory pilot study.
AB  - The impact of nurse practitioners (NPs) in home care on emergency department (ED)
      usage in Canada has not been documented in the literature. This article discusses
      the potential impact of care provided by NPs on ED use for home care patients in
      Canada. The authors used a 2-group prospective design for this pilot study to
      compare the number of ED visits in home care patients followed by NPs
      (intervention group, n = 30) with those receiving usual care and not followed by
      NPs (control group, n = 9). Data were collected by accessing provincial
      electronic medical records at the time of recruitment and at 3 additional time
      points: 2 weeks, 4 weeks, and 8 weeks. Descriptive statistics and the z-test of 2
      proportions were used to compare the 2 groups. The authors found more ED visits
      were documented in the control group than in the intervention group at 2 and 4
      weeks, but not at 8 weeks. Six subjects dropped out in the intervention group and
      1 in the control group during the study due to death. The number of ED visits was
      reduced at 2 and 4 weeks in the intervention group, but there was no significant
      difference in the death rates between the 2 groups. This study serves as a
      springboard for future studies of NPs in home care in Canada.

PMID- 22374513
TI  - Investigation of the cochlear effects of intratympanic steroids administered
      following acoustic trauma.
AB  - OBJECTIVES/HYPOTHESIS: To electrophysiologically and histomorphologically
      demonstrate the effects of intratympanic corticosteroids administered following
      an acoustic trauma on cochlear hair cells. METHODS: The trial was performed on 16
      Wistar albino rats. The rats underwent distortion product otoacoustic emissions
      (DPOAE) measurement before the acoustic trauma, and subsequently rats were
      exposed to noise. Following acoustic trauma, the otoacoustic emission measurement
      was repeated. The rats were divided into two groups, a study group and a control
      group. The study rats were injected with methylprednisolone via the intratympanic
      route throughout the study. In the control group, the rats were injected daily
      with saline. After performing repeated otoacoustic emission measurements, one rat
      in each of the groups was sacrificed and their cochleae isolated. RESULTS: The
      histological investigation performed after the 1st week revealed a statistically
      significantly higher rate of apoptotic cells in the inner and particularly the
      outer hair cells of the rat cochleae in the control group compared to the study
      group. Early measurement of DPOAE within the 1st week demonstrated significantly
      better amplitudes in the study group compared to controls. The otoacoustic
      emission assessment performed on the 14th day demonstrated statistically similar
      DPOAE values between the two groups. CONCLUSIONS: Intratympanic
      methylprednisolone injection administered following an acoustic trauma appears to
      reduce cochlear outer hair cell loss. The impact on hearing loss is less certain.
      Early measurement of DPOAE within the 1st week shows significantly better
      amplitudes in the study group compared to controls. However at 2 weeks, there is
      no statistically significant difference in DPOAE amplitudes between the study and
      control group.

PMID- 22374514
TI  - Polymer-based tubular microbots: role of composition and preparation.
AB  - The influence of the composition and electropolymerization conditions upon the
      propulsion of new template-prepared polymer-based bilayer microtubular microbots
      is described. The effects of different electropolymerized outer layers, including
      polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), polyaniline (PANI),
      and of various inner catalytic metal surfaces (Ag, Pt, Au, Ni-Pt alloy), upon the
      movement of such bilayer microtubes are evaluated and compared.
      Electropolymerization conditions, such as the monomer concentration and medium
      (e.g. surfactant, electrolyte), have a profound effect upon the morphology and
      locomotion of the resulting microtubes. The most efficient propulsion is observed
      using PEDOT/Pt microbots that offer a record-breaking speed of over 1400 body
      lengths s(-1) at physiological temperature, which is the fastest relative speed
      reported to date for all artificial micro/nanomotors. An inner Pt-Ni alloy
      surface is shown useful for combining magnetic control and catalytic fuel
      decomposition within one layer, thus greatly simplifying the preparation of
      magnetically-guided microbots. Polymer-based microbots with an inner gold layer
      offer efficient biocatalytic propulsion in low peroxide level in connection to an
      immobilized catalase enzyme. Metallic Au/Pt bilayer microbots can also be
      prepared electrochemically to offer high speed propulsion towards potential
      biomedical applications through functionalization of the outer gold surface. Such
      rational template preparation and systematic optimization of highly efficient
      microbots hold considerable promise for diverse practical applications.

PMID- 22374515
TI  - Differences in neuromuscular junctions of laryngeal and limb muscles in rats.
AB  - OBJECTIVES/HYPOTHESIS: Laryngeal muscles are specialized for fine control of
      voice, speech, and swallowing, and may differ from limb muscles in many aspects.
      Because muscles and their controlling motor neurons communicate via neuromuscular
      junctions (NMJs), we hypothesized that NMJs in laryngeal muscles have specialized
      characteristics different from limb muscles. STUDY DESIGN: In vivo study.
      METHODS: Single muscle fibers from 12 Sprague-Dawley rats (six male, six female)
      were used to analyze the postsynaptic side of NMJs from laryngeal thyroarytenoid
      (TA), cricothyroid (CT), posterior cricoarytenoid (PCA), limb soleus (SOL), and
      extensor digitorum longus (EDL) muscles. NMJs were labeled with rhodamine
      conjugated alpha-bungarotoxin. With confocal microscopy, we counted cluster
      fragments and measured the NMJ area, both absolute and normalized (corrected by
      muscle fiber diameter), for at least 10 single fibers from each muscle of each
      animal. Differences between genders were also compared. RESULTS: Cluster
      fragments of postsynaptic NMJs were more numerous in PCA and TA compared to CT,
      SOL, and EDL muscles (P < .01) in both male and female rats. NMJ cluster
      fragments were more numerous in female than in male rats only in the TA muscle (P
      < .01). The absolute area covered by the NMJs showed SOL > EDL > PCA > CT > TA (P
      < .01); however, with normalization the SOL = EDL = PCA > CT = TA. CONCLUSIONS:
      Differences found in NMJ surface and organization between laryngeal and limb
      muscle fibers may relate to specialized laryngeal muscle functions. Differences
      in NMJs between male and female rats were found only in the TA muscle, suggesting
      an underlying mechanism for some gender-specific laryngeal disorders related to
      abnormal TA muscle activity.

PMID- 22374516
TI  - Folic acid-functionalized human serum albumin nanocapsules for targeted drug
      delivery to chronically activated macrophages.
AB  - Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA).
      Recent studies have shown that folate receptor beta (FRbeta) is specifically
      expressed by activated macrophages. Therefore a folate-based nanodevice would
      provide the possibility of delivering therapeutic agents to activated macrophages
      without affecting normal cells and tissues. This study shows for the first time
      the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking
      chemicals and emulsifiers used in other methods. Production of HSA nanocapsules
      was optimized leading to a diameter of 443.5 +/- 9.0 nm and a narrow size
      distribution indicated by a polydispersity index (PDI) of 0.066 +/- 0.080.
      Nanocapsules were surface modified with folic acid (FA) and the FA content was
      determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the
      surplus of FA employed. Dynamic light scattering was used to determine size, PDI
      and zetapotential of the produced nanocapsules before and after surface
      modification. FA distribution on the surface of HSA nanocapsules was localized
      three-dimensionally after fluorescence labeling using confocal laser scanning
      microscopy (CLSM). Furthermore, specific binding and internalization of HSA
      nanocapsules by FRbeta-positive and FRbeta-negative macrophages, obtained from
      human peripheral blood mononuclear cells, was demonstrated by flow cytometry.
      FRbeta-expressing macrophages showed an increased binding for FA-modified
      capsules compared with those without FA.

PMID- 22374517
TI  - Heterogeneous reactivity of chlorine atoms with ammonium sulfate and ammonium
      nitrate particles.
AB  - In this laboratory study, model particles of ammonium sulfate (AS) and ammonium
      nitrate (AN) were exposed to chlorine atoms and uptake experiments were performed
      in a coated wall flow tube reactor coupled to a molecular beam mass spectrometer.
      The reactive surfaces were prepared by coating the inner surface of the reactor
      using two different methods: either by depositing size-selected particles on the
      halocarbon wax or by spray depositing thin films using a constant output
      atomizer. The observed uptake coefficients vary for (NH(4))(2)SO(4), ranging from
      gamma(Cl)(AS)~ 1 * 10(-3) for size-selected particles to gamma(Cl)(AS)~ 6 * 10(
      2) for thin films prepared by spray. An uptake coefficient of gamma(Cl)(AN)~ 2.5
      * 10(-3) of Cl on size-selected NH(4)NO(3) particles was measured. A
      heterogeneous recombination of Cl atoms to from Cl(2) molecules was observed for
      the two surfaces. Furthermore, an ageing process was observed for AS particles,
      this phenomenon leading to the formation of new chlorine species on the solid
      substrate.

PMID- 22374518
TI  - Estrogen receptor alpha attenuates therapeutic efficacy of paclitaxel on breast
      xenograft tumors.
AB  - Through transfection of ERalpha into ERalpha- breast cancer BCap37 cells, we
      previously established a pair of isogenic ERalpha-/ERalpha+ tumor cell lines BC
      V/BC-ER, and demonstrated that ERalpha induces chemoresistance in vitro. The
      present study is designed to investigate whether this ERalpha-mediated
      chemoresistance also occurs in xenograft models. Meanwhile, we would test whether
      fulvestrant, a clinically-used antiestrogen agent, can reverse ERalpha-mediated
      chemoresistance in vivo. Xenograft models were established through
      transplantation of BC-ER and BC-V cells into nude mice. Mice were then treated
      with vehicle, paclitaxel, with or without administration of estrogen (E2). The
      potential influence of E2/ERalpha on the therapeutic efficacy of paclitaxel was
      then evaluated. Furthermore, we investigated whether fulvestrant can sensitize
      ERalpha+ tumors to paclitaxel in vivo. Compared with the group treated with PTX
      alone, co-treatment of E2 significantly reduced the therapeutic efficacy of
      paclitaxel in BC-ER tumors (51.23 vs. 36.71%, p < 0.01). Biochemical studies
      demonstrated that E2 significantly interfered with paclitaxel's cytotoxicity in
      BC-ER tumors. Importantly, we found that fulvestrant significantly repressed
      ERalpha expression, potentiated paclitaxel-induced apoptosis and sensitized BC-ER
      tumors to PTX in the presence of E2 (39.12 vs. 53.64%, p < 0.01). In summary,
      this study demonstrated that E2/ERalpha attenuates therapeutic efficacy of
      paclitaxel in an isogenic ERalpha+ xenograft model. Furthermore, we demonstrated
      that fulvestrant significantly reversed the ERalpha-mediated chemoresistance in
      vivo. These findings may have potential implications on the clinical practice of
      antiestrogen and chemotherapeutic agents.

PMID- 22374519
TI  - [Overview--disorders in erythrocyte system].

PMID- 22374520
TI  - [Aplastic anemia and pure red cell aplasia].

PMID- 22374521
TI  - [Paroxysmal nocturnal hemoglobinuria].

PMID- 22374522
TI  - [Iron overload and iron chelation therapy].

PMID- 22374523
TI  - [Overview--disorders in bone marrow].

PMID- 22374524
TI  - [State-of-the-art chemotherapy for acute myeloid leukemia].

PMID- 22374525
TI  - [MDS].

PMID- 22374526
TI  - [Myeloproliferative neoplasms (including chronic myeloid leukemia)].

PMID- 22374527
TI  - [CAG-GO therapy for patients with relapsed or primary refractory CD33-positive
      acute myelogenous leukemia].
AB  - We previously tested a less toxic CAG regimen consisting of low-dose cytarabine,
      aclarubicin and granulocyte-colony stimulating factor for the treatment of
      patients with relapsed or refractory myeloid malignancies or elderly patients
      with untreated ones, obtaining a satisfactory complete remission rate of 62%.
      Gemtuzumab ozogamicin, an anti-CD33 monoclonal antibody conjugated to
      calicheamicin, has recently been approved as a single agent in Japan for the
      treatment of relapsed/refractory CD33-positive acute myelogenous leukemia (9
      mg/m(2) on days1 and 15). Complete remission rate was reported as 30% in a phase
      2 trial in Japan. In this study, effectiveness and safety of combining dose
      attenuated gemtuzumab ozogamicin (3 mg/m(2) on day5) and original CAG regimen
      were assessed in nine patients with relapsed/refractory CD33-positive acute
      myelogenous leukemia and a median age of 70 years. Rate of complete remission
      with or without platelet recovery was 44% (4/9). The median duration of complete
      remission and overall survival were 5.5 and 16 months, respectively. Reversible
      myelosuppression and liver toxicity were the main adverse events, but no regimen
      related death was recorded. Although only a small number of cases were included
      in this preliminary study, this CAG-GO regimen was found to be feasible and
      useful even in high-risk relapsed or refractory patients.

PMID- 22374528
TI  - [Marked improvement of anemia during treatment with deferasirox in patients with
      primary myelofibrosis and acute myeloid leukemia with myelodysplasia-related
      changes].
AB  - We report two patients who achieved a marked improvement of hematopoiesis with
      the use of deferasirox (DSX) for transfusional iron overload. Case 1 is an 81
      year-old male who was diagnosed with primary myelofibrosis in July, 2007. He
      required regular red blood cell (RBC) transfusion of 4 units/month when he was
      started on DSX treatment in June, 2009. Four months after the treatment, he
      became transfusion independent, and has maintained hemoglobin levels of around 13
      g/dl until today. Case 2 is a 70-year-old female with acute myeloid leukemia with
      myelodysplasia-related changes. She had been on RBC transfusion of 4 units/month
      when she was started on DSX treatment in January, 2010. Two months after the
      treatment, she became transfusion-independent, and 5 months after treatment,
      blast cells completely disappeared in the peripheral blood, together with
      normalization of white blood cell and neutrophil counts. Achieving durable
      transfusion-independency and normalization of white blood cell count and
      differential with a single use of DSX is a very rare event. Prospective
      accumulation of more patients and research to understand the mechanism underlying
      these effects are clearly warranted.

PMID- 22374529
TI  - [Idiopathic hypereosinophilic syndrome in a child with fever and hepatomegaly].
AB  - Idiopathic hypereosinophilic syndrome (IHES) in children is a rare disorder. A 1
      year-old girl presented to our hospital for evaluation of eosinophilia. At the
      onset, her white blood cell count in peripheral blood was 70,600/MUl with 74%
      eosinophils. She had a high fever and mild hepatomegaly but had no remarkable
      evidence of organ involvement by CT, MRI and ultrasonography. She was diagnosed
      with IHES without any evidence of secondary eosinophilia, expression of the
      FIP1L1-PDGFRalpha fusion transcript, chromosomal abnormalities, and aberrant T
      cell populations. The serum IgE, vitamin B12, IL-5 and TARC levels were normal.
      Systemic administration of corticosteroid and suplatast tosilate resolved the
      symptoms promptly and resulted in improvement of eosinophilia.

PMID- 22374530
TI  - [Sequential monitoring of plasma EBV-DNA level in a patient with EBV-positive
      Hodgkin lymphoma].
AB  - A 58-year-old woman was admitted to our hospital because of fever, systemic
      lymphadenopathy with abnormal Epstein-Barr virus (EBV) antibody titers, and a
      high EBV-DNA load in the serum. She had been diagnosed as possibly having chronic
      active EBV infection (CAEBV) during a previous hospitalization. The EBV-DNA load
      of the plasma (pEBV-DNA), examined at our hospital, was elevated to 1.8*10(4)
      copies/ml, whereas that of the peripheral blood mononuclear cells was 3.4*10(1)
      copies/MUg DNA, which was not clearly elevated, unlike in cases with CAEBV.
      Biopsy of the cervical lymph node was performed and the diagnosis of mixed
      cellularity classical Hodgkin lymphoma, Stage4B was made. Hodgkin cells were
      positive for EBV. COPP therapy was started and pEBV-DNA decreased drastically.
      The treatment was followed by ABVD therapy and pEBV-DNA turned negative after one
      course of ABVD therapy. She achieved complete response after 4 courses of the
      treatment. Reports from abroad indicate that pEBV-DNA parallels the disease state
      of EBV-positive Hodgkin lymphoma. Our results were consistent with these reports,
      and demonstrated that, in a Japanese patient, EBV-DNA load and its localization
      in the peripheral blood fractions could be useful tools for diagnosis as well as
      evaluating the disease status.

PMID- 22374531
TI  - [Successful treatment with bortezomib for a patient with plasma cell leukemia
      accompanied by severe hyperbilirubinemia].
AB  - A 59-year-old woman was admitted to our hospital with jaundice, renal
      dysfunction, anemia and hypercalcemia. Primary plasma cell leukemia (PCL) was
      diagnosed based on findings of IgA-lambda type M-protein, 22% plasma cells in the
      bone marrow and 23.1% plasma cells of WBC in the peripheral blood. Because the
      total bilirubin (T.Bil) level increased even after the administration of
      prednisolone (PSL), dexamethasone and methylprednisolone, the patient was started
      on bortezomib (0.7 mg/m(2) on days 1, 4, 8 and 11 for 3 weeks) combined with PSL
      (40 mg/day). The level of T.Bil decreased and the patient's condition remarkably
      improved. We then increased the dose of bortezomib to 1.0 mg/m(2) in the second
      course, but discontinued treatment just after starting the third course because
      NCI-CTCAE Grade 3 peripheral neuropathy developed. According to the criteria of
      the International Myeloma Working Group, the response category was VGPR (=very
      good partial response) at 1 month after pausing treatment. We recommend these
      novel agents for PCL, which is an aggressive form of extramedullary plasma cell
      cancer.

PMID- 22374532
TI  - [Successful treatment of acute promyelocytic leukemia complicated with autoimmune
      hepatitis-induced portal hypertension with all-trans retinoic acid].
AB  - A 35-year-old man admitted to the hospital for oral hemorrhage was diagnosed with
      acute promyelocytic leukemia (APL). Remission from APL was achieved by induction
      therapy with all-trans retinoic acid (ATRA); the PML/RARA fusion gene was not
      detected on PCR analysis. Despite complete molecular remission, severe persistent
      pancytopenia, massive ascites, and renal failure were observed. The liver surface
      appeared rough and irregular on computed tomographic images. On the basis of the
      liver biopsy results, we diagnosed his condition as portal hypertension due to
      autoimmune hepatitis. Indocyanine green test showed good residual function of the
      liver, and therefore, 2 courses of consolidation therapy were administered;
      chemotherapy was stopped because of severe pancytopenia due to portal
      hypertension. Instead of continuing the consolidation therapy, maintenance
      therapy involving 8 rounds of ATRA monotherapy (45 mg/m(2), days1~14) was
      initiated. Portal hypertension did not progress further with this maintenance
      therapy and therefore it was continued. The patient has been in remission from
      APL ever since, and no relapses have occurred since the past 5 years. These
      results suggest that ATRA can be used for long-term therapy in such cases.

PMID- 22374533
TI  - [Exacerbation of cranial nerurological symptoms by platelet transfusion before
      the diagnosis of thrombotic thrombocytopenic purpura].
AB  - A 47-year-old woman was transported to our hospital because of vomiting and
      syncope after breakfast. Physical examination revealed icterus and anemia of
      bulbar conjunctivas, and abnormal neurological findings were detected. Laboratory
      data indicated marked anemia and thrombocytopenia (Hb 5.2 g/dl, Plt.
      0.6*10(4)/MUl), but no leukocyte abnormalities were found. Transaminase was
      slightly elevated, and serum indirect bilirubin in was also elevated. Based on
      these data, we initially suspected Evan's syndrome, which involves idiopathic
      thrombocytopenic purpura with autoimmune hemolytic anemia. So we transfused red
      blood cells, performed platelet transfusion, and administered steroids, but there
      was no response to these therapies. On the 4th day of admission, she developed a
      stroke followed by coma. After the stroke, we diagnosed the case as thrombotic
      thrombocytopenic purpura (TTP) because laboratory findings showed diminished
      activity of ADAMTS 13 (a disintegrin-like metalloproteinase with thrombospondin
      type 1 motifs 13) and ADAMTS 13 antigen. It is important to suspect TTP when
      hemolytic anemia with thrombocytopenia is observed, and to check the activity and
      antigen of ADAMTS13 immediately for the diagnosis. Platelet transfusion should be
      done cautiously in these cases.

PMID- 22374534
TI  - [Early onset of anti- erythropoietin antibody-mediated pure red cell aplasia
      after commencement of subcutaneous administration of epoetin-beta].
AB  - We report a 73-year-old Japanese man with early onset pure red cell aplasia
      (PRCA) caused by subcutaneous administration of recombinant epoetin-beta. Two
      months after the start of epoetin therapy, he developed PRCA. Anti-erythropoietin
      (EPO) antibody, detected in the patient's serum by enzyme immunoassay and
      radioimmunoprecipitation method, inhibited EPO-dependent growth of AS-E2 cells in
      vitro. Treatment with prednisone (1 mg/kg) significantly reduced antibody levels
      3 months later. It is important to have an awareness of antibody-mediated PRCA.
      Our case shows that subcutaneous epoetin administration produces this
      complication in the early period of therapy.

PMID- 22374535
TI  - Effects of progesterone on reproduction and embryonic development in the fathead
      minnow (Pimephales promelas).
AB  - High concentrations (375 ng/L) of the steroid hormone progesterone (P4) were
      measured in snowmelt runoff associated with large livestock-feeding operations in
      Wisconsin. To gain insight into the potential endocrine-disrupting effects of P4
      in fish, experiments were conducted to evaluate the effects of short-term
      exposure to environmentally relevant concentrations of P4 on reproduction and
      embryonic development in the fathead minnow (Pimephales promelas). For the
      reproduction assay, groups of reproductively mature fish were exposed for 21 d to
      nominal concentrations of 0, 10, 100, and 1,000 ng/L P4 in a flow-through system,
      and various key reproductive endpoints (e.g., egg number, fertilization success)
      were quantified throughout the exposure period. The embryonic development assay
      consisted of incubating fathead minnow eggs in static culture to quantify the
      effects of P4 on early development and hatching success. Progesterone caused dose
      dependent decreases in fecundity and fertility and significantly reduced
      gonadosomatic index and vitellogenin gene expression in females. There were no
      effects of P4 on early embryonic development or hatching success. Progesterone
      may be a significant endocrine-disrupting chemical in fish.

PMID- 22374536
TI  - 3D segmentation of SBFSEM images of neuropil by a graphical model over supervoxel
      boundaries.
AB  - The segmentation of large volume images of neuropil acquired by serial sectioning
      electron microscopy is an important step toward the 3D reconstruction of neural
      circuits. The only cue provided by the data at hand is boundaries between
      otherwise indistinguishable objects. This indistinguishability, combined with the
      boundaries becoming very thin or faint in places, makes the large body of work on
      region-based segmentation methods inapplicable. On the other hand, boundary-based
      methods that exploit purely local evidence do not reach the extremely high
      accuracy required by the application domain that cannot tolerate the global
      topological errors arising from false local decisions. As a consequence, we
      propose a supervoxel merging method that arrives at its decisions in a non-local
      fashion, by posing and approximately solving a joint combinatorial optimization
      problem over all faces between supervoxels. The use of supervoxels allows the
      extraction of expressive geometric features. These are used by the higher-order
      potentials in a graphical model that assimilate knowledge about the geometry of
      neural surfaces by automated training on a gold standard. The scope of this
      improvement is demonstrated on the benchmark dataset E1088 (Helmstaedter et al.,
      2011) of 7.5billionvoxels from the inner plexiform layer of rabbit retina. We
      provide C++ source code for annotation, geometry extraction, training and
      inference.

PMID- 22374537
TI  - Accuracy of PET-CT in predicting survival in patients with esophageal cancer.
AB  - BACKGROUND: Positron emission tomography (PET) is an integral part of tumor
      staging for patients with esophageal cancer. Recent studies suggest a role for
      PET scan in predicting survival in these patients, but this relationship is
      unclear in the setting of neoadjuvant therapy. We examined pretreatment maximum
      standard uptake value (SUV(max)) of the primary tumor in patients treated with
      and without neoadjuvant therapy. METHODS: All patients undergoing esophagectomy
      with a preoperative PET scan over a nine-year period (2001-2010) were identified
      from a prospectively maintained database. Positron emission tomography data were
      obtained from computers housing the original PET scans. Overall survival was
      correlated with SUV(max) of the primary tumor. RESULTS: A total of 191 patients
      were identified, and 103 patients met inclusion criteria. Eighty-two had an
      adenocarcinoma (80%), and 21 (20%) had a squamous cell carcinoma. Fifty-seven
      (55%) patients received neoadjuvant therapy. In the surgery alone group, a
      SUV(max) of > 5.0 in the primary tumor was associated with poor prognosis [Hazard
      Ratio (HR) 0.32; p = 0.007], but this factor did not retain its significance on
      multivariate analysis (HR 0.65; p = 0.43). Pretreatment SUV(max) in patients who
      underwent neoadjuvant therapy was not significant in predicting overall survival
      (p = 0.10). CONCLUSIONS: This study does not support the use of SUV(max) on
      pretreatment PET scans as a prognostic tool for patients with esophageal cancer,
      especially in those who have received neoadjuvant therapy. Lymph node status is a
      more accurate predictor of outcome, and efforts to improve pretreatment staging
      should focus on this factor.

PMID- 22374538
TI  - Risk associated with bilobectomy after neoadjuvant concurrent chemoradiotherapy
      for stage IIIA-N2 non-small-cell lung cancer.
AB  - BACKGROUND: The aim of the present study was to evaluate the outcomes of surgical
      resection, especially bilobectomy, after chemoradiation therapy to treat stage
      IIIA-N2 non-small-cell lung cancer. METHODS: Data from all patients who underwent
      surgical resection after neoadjuvant chemoradiation therapy for stage IIIA-N2 non
      small-cell lung cancer between 1998 and 2007 were analyzed retrospectively. The
      chemotherapy regimen consisted of weekly paclitaxel plus cisplatin or weekly
      paclitaxel plus carboplatin for 5 weeks. The concurrent thoracic radiotherapy
      dose was 45 Gy over 5 weeks. Surgical resection was planned at around 4 weeks
      following the completion of neoadjuvant therapy. RESULTS: Of 186 patients who
      underwent neoadjuvant therapy, 23 bilobectomies, 28 pneumonectomies, and 135
      lobectomies were performed. The early postoperative mortality rate (within 30
      days after operation) was 7.1, 8.7, and 1.5% for the pneumonectomy, bilobectomy,
      and lobectomy groups, respectively. The late postoperative mortality rate (within
      90 days) of the lobectomy, bilobectomy, and pneumonectomy groups was 5.9, 13, and
      10.7%, respectively. Overall survival was significantly higher among patients
      treated by lobectomy than among those treated by bilobectomy (p = 0.041) or
      pneumonectomy (p = 0.010). Recurrence was significantly lower in patients treated
      by lobectomy than in those treated by pneumonectomy (p = 0.034). CONCLUSIONS:
      Bilobectomy is associated with high operative mortality and poor long-term
      survival after neoadjuvant concurrent chemoradiotherapy for stage IIIA-N2 non
      small-cell lung cancer. The outcomes of bilobectomy were similar to those of
      pneumonectomy in terms of overall survival, disease-free survival, and
      postoperative mortality.

PMID- 22374539
TI  - Esophagogastroduodenoscopy in a public referral hospital in Lilongwe, Malawi:
      spectrum of disease and associated risk factors.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) is a valuable tool for diagnosing
      and treating upper gastrointestinal disease. Prioritizing the use of EGD in
      resource-limited settings must be customized to local populations to maximize
      population benefit from the examination. METHODS: Cross-sectional, retrospective
      review of EGD reports was conducted at Kamuzu Central Hospital (KCH), Lilongwe,
      Malawi. Esophageal tumors were defined as obstructive or nonobstructive and
      esophageal varices were graded on a scale of I to IV. Descriptive statistics were
      calculated and logistic regression performed for each disease state compared with
      all other reports. RESULTS: A total of 1,034 cases were reviewed (56% male; mean
      age (standard deviation), 44 (17) years). The most common indications were
      dysphagia (37%), hematemesis (21%), and epigastric pain (16%). The most common
      diagnoses were normal (36%), esophageal cancer (27%), and esophageal varices
      (17%). Eighty-six percent of esophageal tumors were obstructive and 45% of
      esophageal varices were grade III or IV. Normal examinations were more likely to
      be female, younger, and present with dyspepsia. Esophageal cancers were more
      likely to be male, older, present with dysphagia, and present from districts
      outside Lilongwe. Esophageal varices were more likely to present with
      hematemesis. CONCLUSIONS: EGD is a limited resource at KCH; patient selection
      should be guided by patient age and indication. The high burden of esophageal
      cancer and varices in Malawi suggests that therapeutic endoscopy would be
      beneficial.

PMID- 22374540
TI  - Donor age affects liver regeneration during early period in the graft liver and
      late period in the remnant liver after living donor liver transplantation.
AB  - BACKGROUND: The aim of the present study was to evaluate the influence of donor
      age on liver regeneration and surgical outcomes in recipients and donors.
      PATIENTS AND METHODS: Among 101 cases of adult-to-adult living donor liver
      transplantation (LDLT) between March 2002 and March 2011, according to donor age:
      younger (Y) <50 years of age or older (O) >= 50 years of age, the donors and
      recipients using right (R) or left (L) graft were divided into groups Y/R (n =
      51) and O/R (n = 17), and groups Y/L (n = 26) and O/L (n = 7), respectively.
      Remnant liver volume (RemLV) and graft liver volume (GLV) were estimated by
      computed tomography (CT) volumetry. A disintegrin and metalloprotease with
      thrombospondin type I domain 13 (ADAMTS13) activities and von Willebrand factor
      (vWF) antigen levels were measured as factors reflecting thrombotic
      microangiopathy. RESULTS: Among the donors, RemLV/total liver volume (TLV) was
      lower in group O/R than in group Y/R, although there were no significant
      differences by t-test with the Bonferroni correction (rough p value = 0.02 at 6
      months and rough p value > 0.05 at 1, 3, and 12 months). Donor age (>= 50 years)
      was independently correlated with impaired remnant liver regeneration at 6 months
      in right lobe LDLT (p = 0.04). Among the recipients, GLV/standard liver volume
      (SLV) was lower during the first month, although there were no significant
      differences between the two groups by t-test with the Bonferroni correction
      (rough p value = 0.03 at 1 week and rough p value >0.05 at 2 weeks and 1 and 3
      months). Donor age (>= 50 years) was independently correlated with impaired graft
      liver regeneration at 1 week in both right and left lobe LDLT (p < 0.05).
      ADAMTS13 activities were lower in group O/R than in group Y/R, although there
      were no significant differences by t-test with the Bonferroni correction (rough p
      value = 0.049 on postoperative days (POD) 1 and 28 and rough p value >0.05 on POD
      7 and 14). vWF/ADAMTW13 ratios were higher on POD 14, although there were no
      significant differences between the two groups by t-test with the Bonferroni
      correction (rough p value = 0.044 on POD 14 and rough p value >0.05 on POD 1, 7,
      14, and 28). CONCLUSIONS: The surgical outcomes using older donor livers for LDLT
      were comparable to those using younger donor livers. When using older donor
      livers, however, we should pay attention to the liver volume for recipients as
      well as donors, because older donor livers might have impaired regenerative
      ability.

PMID- 22374542
TI  - Short bowel syndrome: a practical pathway leading to successful enteral autonomy.
AB  - BACKGROUND: Short bowel syndrome is a multisystemic disorder that results from
      the loss of a significant amount of small bowel. The goal of treatment in these
      patients is to achieve complete enteral autonomy while minimizing complications.
      Our unit has 30 years of experience in the management of short gut patients.
      During the past decade, our results have improved significantly, especially in
      children with severe short bowel syndrome. This brief communication looks at the
      algorithm presently used in our unit. METHODS: In this communication, the
      principles in management of short bowel syndrome in our unit are discussed. In
      addition, our algorithm is published for the first time. A brief summary of our
      results is provided. RESULTS: Twenty-seven children were enrolled from 2000 to
      2009. In this cohort, two patients died because of significant liver disease: one
      after having two liver and bowel transplants. Overall, survival stands at 92%.
      All had autologous gastrointestinal reconstruction, and 19 patients underwent
      bowel lengthening (longitudinal intestinal lengthening and tailoring). The median
      residual length of bowel of this subgroup at first operation was 25 cm in those
      who had their gut measured. Two patients were lost to follow-up. Two patients
      remain on supplemental total parenteral nutrition (TPN), with an overall 91% of
      surviving patients off TPN at a median of 6 months after reconstruction.
      CONCLUSIONS: We believe this improvement is related to the development-over many
      years-of a structured pathway for managing these patients.

PMID- 22374541
TI  - Role of caudate lobectomy in type III A and III B hilar cholangiocarcinoma: a 15
      year experience in a tertiary institution.
AB  - BACKGROUND: Concomitant liver resection for type III hilar cholangiocarcinoma
      could improve the R0 resection rate and long-term outcome. In the present study,
      we examine the specific role of caudate lobectomy in liver resection for type
      III(A) and III(B) hilar cholangiocarcinoma and the prognostic factors for
      survival in this group of patients. METHODS: We reviewed all patients with type
      III(A) and III(B) hilar cholangiocarcinoma who underwent liver resection in
      Samsung Medical Center from January 1995 to July 2010. Patients were divided into
      those with and without caudate lobectomy (CL). The log rank test and Cox
      regression analysis were employed to investigate for prognostic factors of
      survival. RESULTS: There were 127 patients in this cohort, 57 without CL (44.9%)
      and 70 with CL (55.1%). The demographics and symptoms of presentation were
      comparable. The median preoperative bilirubin level was significantly higher in
      the group undergoing CL (p = 0.017). Patients with CL had a significantly better
      overall survival (OS) (CL: 64.0 months vs without CL: 34.6 months) (p = 0.010)
      and disease-free survival (DFS) (CL: 40.5 months vs without CL: 27.0 months) (p =
      0.031). Multivariate analysis showed that presence of symptoms (p = 0.025) and
      positive lymph node (LN) metastasis (p < 0.001) were negative prognostic factors
      for OS. Furthermore, multivariate analysis for DFS found that caudate lobectomy
      (p = 0.016) and positive LN metastasis (p = 0.001) were positive and negative
      prognostic factors, respectively. CONCLUSIONS: Caudate lobectomy contributed to
      improvement of DFS and OS in type III hilar cholangiocarcinoma. Other prognostic
      factors include positive LN metastasis and presence of symptoms.

PMID- 22374543
TI  - Predictors of the development of surgical complications among hematopoietic stem
      cell transplantation recipients.
AB  - BACKGROUND: This study was designed to determine possible risk factors for the
      development of surgical complications after hematopoietic stem cell
      transplantation (HSCT). HSCT carries the possibility for the development of
      surgical morbidities and mortalities; certain populations of patients are at
      higher risk for developing complications. Defining those risk factors will help
      surgeons to anticipate and manage these complications. METHODS: The records of
      165 patients at King Hussein Cancer Center (KHCC) were reviewed from January 2007
      to December 2008. Patients' characteristics, including age, source and type of
      transplant, behavior of disease, total body irradiation (TBI), immunity status,
      and intensity of conditioning were studied. RESULTS: According to our data,
      abdominal complications were more common among patients who received TBI versus
      patients who did not, and in patients who received peripheral blood versus bone
      marrow and cord blood as the source of stem cells. Ear, nose, and throat (ENT)
      complications were found more in patients who underwent nonmyeloablation
      conditioning. Catheter-related complications were found more significantly in
      immune-compromised patients during the post-engraftment period. We also found
      that ENT complications were more frequent in patients with cord blood as the
      source of stem cells, although the results are inconclusive due to the small
      sample size. CONCLUSIONS: Pretransplantation factors can be used as predictors
      for the development of surgical complications in HSCT recipients. Abdominal
      complications were significantly more common in patients who received total body
      irradiation as part of their conditioning regimen and when the peripheral blood
      was a source for stem cell transplantation.

PMID- 22374544
TI  - Transvaginal specimen extraction after laparoscopic colectomy.
AB  - BACKGROUND: Despite the advantages of laparoscopic colon surgery, the need for an
      incision in the abdominal wall to remove the surgical specimen is a morbidity
      factor. The objective of this article is to introduce transvaginal specimen
      extraction after laparoscopic colectomy, in order to avoid an abdominal incision.
      METHODS: Between 2008 and 2011, 21 selected women with benign and malignant
      colorectal pathologies underwent laparoscopic colectomy and the extraction of the
      surgical specimen was done through a transvaginal access route. Of these
      patients, 12 had symptomatic diverticular disease, four had rectal villous
      adenomas, two had severe chronic constipation, and three had adenocarcinomas. We
      describe the surgical technique and the short-term outcomes related to the
      transvaginal specimen extraction. RESULTS: The procedure was successful in all
      cases. There were no immediate complications or mortality. At follow-up, between
      2 and 34 months, there were no functional disorders associated with the
      transvaginal specimen extraction. CONCLUSION: Specimen removal of laparoscopic
      colectomies via the transvaginal route avoids the abdominal wall incision and its
      potential complications. It is feasible, safe, and simple to perform, with no
      additional costs, and provides excellent cosmetic results.

PMID- 22374545
TI  - Effects of post-transplant enteral nutrition with an immunomodulating diet
      containing hydrolyzed whey peptide after liver transplantation.
AB  - BACKGROUND: Complications due to infections, including bacteremia, often arise
      after liver transplantation (LT) and are the most frequent causes of in-hospital
      death. Hydrolyzed whey peptide (HWP), a protein complex derived from milk, has
      anti-inflammatory effects. The present study retrospectively analyzes the effects
      of early enteral nutrition with a new immunomodulating diet (IMD) enriched with
      HWP in patients after living-donor LT (LDLT). METHODS: Data from 76 consecutive
      adult patients who underwent LDLT at our institute between September 2009 and
      March 2011 were retrospectively analyzed. The new IMD enriched with HWP and a
      conventional elemental diet were administered enterally to 40 (HWP group) and 36
      (control group) patients, respectively, within the first 24 h after surgery.
      RESULTS: The characteristics of patients and surgical parameters did not differ
      between the two groups. The incidence of bacteremia was significantly lower in
      the HWP (15%) than in the control group (47%) (p = 0.002). The in-hospital
      mortality due to infection was a little lower in the HWP group than in the
      control group, although there was no statistical difference (p = 0.145). The
      fasting blood glucose level at postoperative day 7 was significantly lower in the
      HWP group than in the control group (p = 0.005). The incidence of acute cellular
      rejection was similar between the two groups (p = 0.858). CONCLUSION: Early
      enteral nutrition with the new IMD enriched with HWP can prevent post-transplant
      bacteremia and post-transplant hyperglycemia without increasing the incidence of
      acute cellular rejection.

PMID- 22374546
TI  - The utility of ultrasonography in the management of undescended testis in a
      developing country.
AB  - BACKGROUND: The use of ultrasonography to localize the testis in children with
      undescended testis is still controversial. This study was designed to determine
      the value of ultrasound in the preoperative assessment of children with
      undescended testis in a resource-limited setting. METHODS: A retrospective
      evaluation of all boys undergoing operation for undescended testes at the
      University of Nigeria Teaching hospital Enugu from June 2005 to December 2009 was
      performed. The operative findings were compared with the preoperative findings on
      clinical and ultrasound examinations. RESULTS: Overall, 49 boys with 60
      undescended testes (unilateral in 38, and bilateral in 11 cases) were operated on
      during the study period. The median age of the patients was 5 (range, 1-14)
      years. At operation, 39 (65%) testes were located at the inguinal region, 17
      (28.3%) were intra-abdominal, and 4 (6.7%) were vanishing testes. Of the inguinal
      testes, 30 (77%) were clinically palpable, and 38 (97.4%) accurately localized by
      ultrasound (p = 0.006). The intra-abdominal testes, the vanishing testes, and one
      inguinal testis were not identified with ultrasound. However, two testes
      identified as inguinal by ultrasound were found intraabdominal at operation, and
      two of the vanishing testes were recognized as viable testes by ultrasound.
      CONCLUSIONS: Ultrasound may identify some otherwise nonpalpable inguinal testes
      and hence affect therapeutic approach. It may, however, be unhelpful in truly
      abdominal and vanishing testes.

PMID- 22374547
TI  - Fast neutron relative biological effects and implications for charged particle
      therapy.
AB  - In two fast neutron data sets, comprising in vitro and in vivo experiments, an
      inverse relationship is found between the low-linear energy transfer (LET)
      alpha/beta ratio and the maximum value of relative biological effect (RBE(max)),
      while the minimum relative biological effect (RBE(min)) is linearly related to
      the square root of the low-LET alpha/beta ratio. RBE(max) is the RBE at near zero
      dose and can be represented by the ratio of the alpha parameters at high- and low
      LET radiation exposures. RBE(min) is the RBE at very high dose and can be
      represented by the ratio of the square roots of the beta parameters at high- and
      low-LET radiation exposures. In principle, it may be possible to use the low-LET
      alpha/beta ratio to predict RBE(max) and RBE(min, )providing that other LET
      related parameters, which reflect intercept and slopes of these relationships,
      are used. These two limits of RBE determine the intermediate values of RBE at any
      dose per fraction; therefore, it is possible to find the RBE at any dose per
      fraction. Although these results are obtained from fast neutron experiments,
      there are implications for charged particle therapy using protons (when RBE is
      scaled downwards) and for heavier ion beams (where the magnitude of RBE is
      similar to that for fast neutrons). In the case of fast neutrons, late reacting
      normal tissue systems and very slow growing tumours, which have the smallest
      values of the low-LET alpha/beta ratio, are predicted to have the highest RBE
      values at low fractional doses, but the lowest values of RBE at higher doses when
      they are compared with early reacting tissues and fast growing tumour systems
      that have the largest low-LET alpha/beta ratios.

PMID- 22374548
TI  - Accelerator science in medical physics.
AB  - The use of cyclotrons and synchrotrons to accelerate charged particles in
      hospital settings for the purpose of cancer therapy is increasing. Consequently,
      there is a growing demand from medical physicists, radiographers, physicians and
      oncologists for articles that explain the basic physical concepts of these
      technologies. There are unique advantages and disadvantages to all methods of
      acceleration. Several promising alternative methods of accelerating particles
      also have to be considered since they will become increasingly available with
      time; however, there are still many technical problems with these that require
      solving. This article serves as an introduction to this complex area of physics,
      and will be of benefit to those engaged in cancer therapy, or who intend to
      acquire such technologies in the future.

PMID- 22374549
TI  - The potential impact of relative biological effectiveness uncertainty on charged
      particle treatment prescriptions.
AB  - There continues to be uncertainty regarding the relative biological effectiveness
      (RBE) values that should be used in charged particle radiotherapy (CPT)
      prescriptions using protons and heavier ions. This uncertainty could potentially
      offset the physical dose advantage gained by exploiting the Bragg peak effect and
      it needs to be clearly understood by clinicians and physicists. This paper
      introduces a combined radiobiological and physical sparing factor (S). This
      factor includes the ratio of the most relevant physical doses in tumour and
      normal tissues in combination with their respective RBE values and can be
      extended to contain the uncertainties in RBE. S factors can be used to study, in
      a simplified way for tentative modelling, those clinical situations in which high
      linear energy transfer (LET) irradiations are likely to prove preferable over
      their low-LET counterparts for a matched tumour iso-effect. In cases where CPT
      achieves an excellent degree of normal tissue sparing, the radiobiological
      factors become less important and any uncertainties in the tumour and healthy
      tissue RBE values are correspondingly less problematic. When less normal tissue
      sparing can be achieved, however, the RBE uncertainties assume greater relevance
      and will affect the reliability of the dose-prescription methodology. More
      research is required to provide accurate RBE estimation, focusing attention on
      the associated statistical uncertainties and potential differences in RBE between
      different tissue types.

PMID- 22374550
TI  - Malignant induction probability maps for radiotherapy using X-ray and proton
      beams.
AB  - The aim of this study was to display malignant induction probability (MIP) maps
      alongside dose distribution maps for radiotherapy using X-ray and charged
      particles such as protons. Dose distributions for X-rays and protons are used in
      an interactive MATLAB(r) program (MathWorks, Natick, MA). The MIP is calculated
      using a published linear quadratic model, which incorporates fractionation
      effects, cell killing and cancer induction as a function of dose, as well as
      relative biological effect. Two virtual situations are modelled: (a) a tumour
      placed centrally in a cubic volume of normal tissue and (b) the same tumour
      placed closer to the skin surface. The MIP is calculated for a variety of
      treatment field options. The results show that, for protons, the MIP increases
      with field numbers. In such cases, proton MIP can be higher than that for X-rays.
      Protons produce the lowest MIPs for superficial targets because of the lack of
      exit dose. The addition of a dose bath to all normal tissues increases the MIP by
      up to an order of magnitude. This exploratory study shows that it is possible to
      achieve three-dimensional displays of carcinogenesis risk. The importance of
      treatment geometry, including the length and volume of tissue traversed by each
      beam, can all influence MIP. Reducing the volume of tissue irradiated is
      advantageous, as reducing the number of cells at risk reduces the total MIP. This
      finding lends further support to the use of treatment gantries as well as the use
      of simpler field arrangements for particle therapy provided normal tissue
      tolerances are respected.

PMID- 22374551
TI  - Impact of mental disorders on work performance in a community sample of workers
      in Japan: the World Mental Health Japan Survey 2002-2005.
AB  - Most studies that investigate the impact of mental disorders on work performance
      have been conducted in Western countries, but this study examines the impact of
      common mental disorders on sick leave and on-the-job work performance in a
      community sample of Japanese workers. Data from the World Mental Health Japan
      survey were analyzed. A subsample of 530 workers aged 20-60years were interviewed
      using the WHO Composite International Diagnostic Interview 3.0. The WHO Health
      and Work Performance Questionnaire, was used to assess sick days and on-the-job
      work performance for the previous 30days. Linear regression was used to estimate
      the impact of mental disorders on these indicators of work performance over
      12months. Mood disorders, including major depressive disorder, and alcohol
      abuse/dependence were significantly associated with decreased on-the-job
      performance. There were no significant associations between mental disorders and
      sick/absent days. Consistent with previous studies, major depression has a great
      impact on on-the-job work performance in Japan. The lost productivity was
      estimated at approximately 28-30 lost days per year. A similar decrease in on-the
      job work performance was found for alcohol abuse/dependence, which is stronger
      than that in other countries, probably attributable to greater tolerance of
      problematic drinking at Japanese worksites.

PMID- 22374552
TI  - Association between three genetic polymorphisms of glutathione S-transferase Z1
      (GSTZ1) and susceptibility to bipolar disorder.
AB  - The association between polymorphisms of glutathione S-transferase Z1 (GSTZ1) and
      susceptibility to bipolar disorder (BPD) is investigated. This study was
      performed on 228 BPD patients and 234 control subjects. Among early-onset
      patients, the variant alleles of Glu32Lys and G-1002A increased BPD
      susceptibility. The haplotype "-1002G, 32Glu, 42Gly" versus the other haplotypes
      was significantly decreased among early-onset patients compared to controls
      (P=0.016).

PMID- 22374553
TI  - Aberrant sense of agency in patients with schizophrenia: forward and backward
      over-attribution of temporal causality during intentional action.
AB  - Self-disturbances in schizophrenia have been explained and studied from the
      standpoint of an abnormal sense of agency. We devised an agency-attribution task
      that evaluated explicit experiences of the temporal causal relations between an
      intentional action and an external event, without any confounding from sense of
      ownership of body movement. In each trial, a square piece appeared on the bottom
      of a computer screen and moved upward. Subjects were instructed to press a key
      when they heard a beep. When the key was pressed, the piece jumped with various
      temporal biases. Subjects were instructed to make an agency judgment for each
      trial. We demonstrated that an excessive sense of agency was observed in patients
      with schizophrenia compared with normal controls. Moreover, patient groups had a
      greater tendency to feel a sense of agency even when external events were
      programmed to precede their action. Therefore, patients felt both forward and
      backward exaggerated causal efficacy in the temporal event sequence during the
      intentional action. Confusion in the experience of temporal causal relations
      between the self and the external world may underlie self-disturbances in
      schizophrenia.

PMID- 22374554
TI  - Genetic polymorphisms (at codons 194 and 399) in the DNA repair gene XRCC1 and
      susceptibility to bipolar disorder.

PMID- 22374555
TI  - Effects of vitamin A, vitamin A plus zinc, and multiple micronutrients on anemia
      in preschool children in Chongqing, China.
AB  - This study is to clarify the impact of vitamin A or vitamin A combined with other
      micronutrients supplementation on anemia and growth in preschoolers. In the
      present study, a total of 290 preschoolers, aged 36-72 months old were randomly
      assigned to 3 treatment groups: vitamin A (A group), vitamin A plus zinc (AZ
      group), and vitamin A combined with additional multiple-micronutrient (AMM
      group). After 6-month supplementation, the height and height-for-age z-score
      gains of the AZ group were significantly higher than the other groups; the weight
      gain of the AMM group was greater than the other groups. Compared with baseline
      values, the concentrations of hemoglobin, and zinc at the end significantly
      increased in all 3 groups. The incremental concentrations of hemoglobin in the
      AMM group were significant higher than in the other two groups. Furthermore, the
      incremental concentrations of serum retinol in the AMM group, and the increase in
      serum zinc concentrations in the AZ group were significantly higher,
      respectively, than in the other groups. These 3 kinds of supplements in the
      present study are effective in enhancing height gains and are effective in
      reducing the prevalence of anemia. Supplementation of zinc plus vitamin A is a
      better way for improving children's height and height-for-age z-score. Vitamin A
      combined with multiple-micronutrient is more effective in improving the
      hemoglobin concentrations in preschool children.

PMID- 22374556
TI  - Glycemic and oxidative status of patients with type 2 diabetes mellitus following
      oral administration of alpha-lipoic acid: a randomized double-blinded placebo
      controlled study.
AB  - Despite well-controlled blood glucose levels, diabetic complications still
      inevitably take place via several mechanisms including excessive generation of
      free radicals in patients who suffer from diabetes mellitus (DM). A randomized
      double-blind placebo-controlled clinical trial to investigate the effectiveness
      of oral supplementation of DL-alpha-lipoic acid (ALA) on glycemic and oxidative
      status in DM patients was conducted. Thirty eight outpatients with type 2 DM were
      recruited and randomly assigned to either placebo or treatment in various doses
      of ALA (300, 600, 900, and 1200 mg/day) for 6 months. Following the treatment,
      all subjects were evaluated for glucose status and oxidative biomarkers. Results
      showed that fasting blood glucose, HbA1c trended to decrease in a dose-dependent
      manner. Increase of urinary PGF2alpha-Isoprostanes (F2alpha-IsoP) was noted in
      placebo but not ALA-treated groups, indicating possible suppressing action of ALA
      on lipid peroxidation in DM subjects. 8-Hydroxy-2'-deoxyguanosine (8-OHdG)
      levels, however, were similar in both placebo and ALA groups as well as urinary
      microalbumin and serum creatinine. Safety evaluation was monitored and treatment
      was found to be well tolerated despite some minor side effects. Results from this
      study reflected the benefits of ALA in glucose status with slight efficiency on
      oxidative stress-related deterioration in DM patients.

PMID- 22374557
TI  - Behavioral change during weight loss program and one-year follow-up: Saku Control
      Obesity Program (SCOP) in Japan.
AB  - This study evaluated effects of a behavioral approach which placed emphasis on
      tailored behavior counseling, diet, weight loss and weight maintenance. A one
      year randomized controlled trial was conducted among 235 overweight/obese adults
      in Japan. The intervention group (n=119) received individual-based counseling
      using a behavioral approach and the changes made in the diet and physical
      activity were dependent on each participant as much as possible. One year later,
      the intervention group lost significantly more weight than the control group (
      5.0 kg vs. 0.1 kg for men and -3.9 kg vs. -0.2 kg for women). Compared to the
      control group, the male intervention group reduced overall energy, cereals and
      dairy products consumption significantly, while increasing green and yellow
      vegetable intake, and the female intervention group significantly reduced intake
      of dairy products. Regarding behaviors, both male and female intervention groups
      increased the number of walking steps and women improved their irregular eating
      habits compared to those in the control groups. Behavior changes were related to
      weight loss; participants who maintained the action/maintenance stage or moved to
      later stages lost significantly more weight than participants who remained in the
      pre-contemplation/contemplation/preparation stages or regressed to earlier
      stages. After one-year follow-up, the intervention group maintained significantly
      lower weights, lower energy intakes and improvements in irregular eating habits.
      Our behavioral approach led to diet and behavior modification, weight loss and
      maintenance. Because modified variables differed between men and women, gender
      specific approaches may be necessary.

PMID- 22374558
TI  - Rice intake, weight change and risk of the metabolic syndrome development among
      Chinese adults: the Jiangsu Nutrition Study (JIN).
AB  - OBJECTIVES: To examine the association between rice intake, staple food patterns
      (measured by percentage of rice in staple food (PRS)), weight change and the risk
      of the metabolic syndrome development. METHODS: We followed 1231 adults, aged 20
      and older, from 2002 to 2007. Food intake was assessed using a food frequency
      questionnaire. Body weight, height, waist circumference, blood pressure and
      fasting plasma glucose and lipids were measured. The metabolic syndrome was
      defined according to the International Diabetes Federation definition. RESULTS:
      Rice consumption of >=401 g/day was associated with less weight gain (-2.08 kg,
      95%CI: -2.75, -1.41, p<0.001), and 42% less risk of hypertension, as compared to
      rice consumption of <200 g/day (p=0.024). A strong linear association between
      rice intake and hyperglycemia was found: the odd ratios for incident
      hyperglycemia across rice intake <200, 201-400, >=401 g/day were: 1, 1.96, 2.50
      (95%CI: 1.37, 4.57) (p for trend 0.005). A positive association between rice
      intake and incident abnormal high-density lipoprotein was observed. There was no
      association between rice intake and incident high triglycerides. Every 10%
      increase in PRS was associated with a 0.28 kg less in weight gain, 22% increase
      in hyperglycemia risk and 9% decrease in hypertension risk. Rice intake and PRS
      were not associated with the risk of the metabolic syndrome. CONCLUSION: Rice
      intake and PRS were inversely associated with weight gain, and PRS was inversely
      associated with hypertension, but positively associated with fasting blood
      glucose elevation. No association between rice intake and PRS with the metabolic
      syndrome was found.

PMID- 22374559
TI  - Decline in anthropometric evaluation predicts a poor prognosis in geriatric
      patients.
AB  - OBJECTIVE: Malnutrition is frequent in the geriatric population and is often
      undetected and untreated. Although we often use serum albumin as a nutritional
      marker, it has limitations in elderly patients in terms of predicting diseases
      and infections. Anthropometric measurements are not commonly used, despite their
      simple, easy, and effective characteristics. We evaluated the associations
      between anthropometric measurements with other nutritional factors and examined
      its relationship with mortality, decubitus ulcer, length of hospital stay and
      antibiotic usage. RESEARCH METHODS AND PROCEDURES: We enrolled 223 patients,
      performed anthropometric measurements and then followed them for a mean of 24
      months. RESULTS: Patients with hypoalbuminemia but with normal body measurements
      tended to increase serum albumin levels over the next 24 months and had more
      favorable outcomes including being discharged. Patients with normal albumin but
      decreased body measurements resulted in a progressive drop in serum albumin and
      had a higher mortality rate. Additionally, patients with hypoalbuminemia had
      higher antibiotic usage than patients without hypoalbuminemia. Decreases in
      anthropometric measurements were related to mortality, length of hospital stay,
      and decubitus ulcer. CONCLUSIONS: Anthropometric measurements are easily obtained
      and closely associated with mortality, decubitus ulcer, and length of hospital
      stay. Anthropometric measurements used in conjunction with serum albumin are more
      predictive of patient outcome then serum albumin alone.

PMID- 22374560
TI  - Low aglycone content in commercial soy drink products.
AB  - The effectiveness of soy isoflavones to prevent bone loss in postmenopausal women
      is controversial. While consumption of soy in Vietnam is very high, we recently
      reported a prevalence of osteoporosis comparable to that of many Western
      populations. In the present study, we analyzed the isoflavone content of soy
      drink products commercially available in Vietnam and Sweden, and we also compared
      these products to "home-made" soy drink from beans of different origin. The
      amounts of the bioactive aglycones (daidzein, glycitein and genistein) and their
      glycoside isomers were quantified by high-pressure liquid chromatography. We
      found that the total isoflavone content was low in all preparations, around 70
      100 mg/L and of this only 10% were bioactive aglycones. Of these, the Vietnamese
      products contained significantly lower levels of glycitein than the products from
      Sweden and "home-made" soy drink preparations. The results show that consumption
      of several liters of soy drink per day would be needed to achieve threshold
      levels for a protective effect on bone. There was no significant association
      between total protein and isoflavone content in different products. Accurate
      labeling of soy drink and other products eg of aglycone and glycoside content
      would allow health professionals and researchers to better explore the possible
      benefits of soy in dietary intervention studies.

PMID- 22374561
TI  - Preferences of healthy and unhealthy foods among 3 to 4 year old children in
      Mexico.
AB  - OBJECTIVE: To evaluate the preference of healthy and unhealthy foods among pre
      school children attending daycare and its association with that of their parents,
      body mass index and socio-demographic variables. METHODOLOGY: We asked children
      and parents to depict their food preferences through 54 pictures of different
      food items. The association between the preferences and socio-demographic
      variables was done using the Phi correlation, chi-squared, Fisher's correlation,
      as well as univariate and multivariable logistic regression. RESULTS: Two-hundred
      and sixty-five parent-child pairs participated in the study. Ice cream, potato
      chips and lollypops were the foods most preferred by children. On the other hand,
      quince jelly, coffee and avocado were the least preferred. Overweight and obese
      children had a higher preference for quince jelly, preserved fruits, and
      vegetable soup. With univariate logistic regression, children of low-income homes
      (OR= 2.56, p=0.007) and attending public daycare centers (OR= 6.2, p=0.0001)
      preferred less healthy fruits. When the father's education was added in a
      multivariable model including family income, only children whose fathers had <=9
      years of education showed a higher preference for less healthy food. When
      parent's education, family income, and parent's preference for healthy foods were
      included to the model only children attending public daycares were more likely to
      prefer healthy foods. CONCLUSION: The foods most preferred by children have a
      high caloric density. The children's body mass index, their parent's monthly
      income, the father's education and the type of daycare they attended were
      associated with the preference of healthy or unhealthy foods.

PMID- 22374562
TI  - Interactive effects of family socioeconomic status and body mass index on
      depression in school-aged children.
AB  - Depression is an important health problem in children and the onset of depression
      is occurring at a younger age than previously suggested. The associations of
      being overweight and low socioeconomic status in childhood depression have been
      well documented; nevertheless few studies have addressed the combined effects of
      socioeconomic status and body weight, with depression in school-age children. We
      intended to examine if the relationship between socioeconomic status and
      childhood depression could be modified by abnormal body weight. A cross-sectional
      study was performed with a total of 559 subjects from 29 elementary schools in
      Taiwan. A depression scale was used to determine the depression status. Children
      receiving governmental monetary assistance for after-school class were
      categorized as being in the lower socioeconomic group. Data for depression
      related demographic characteristics, family and school variables were collected.
      Children in the lower socioeconomic status group have a higher prevalence of
      depression (23.5%) than those in higher socioeconomic status groups(16.4%). Being
      overweight demonstrates the opposite effect on depression risk in the different
      socioeconomic groups. In lower socioeconomic families, the risk of depression in
      overweight children is three times higher than that for normal weight children;
      whereas in higher socioeconomic families, overweight children have a lower risk
      for depression than normal weight children. We concluded that a qualitative
      interactive effect existed between being overweight and socioeconomic status with
      childhood depression. More attention should be paid to overweight children from
      lower socioeconomic status families to prevent depression in school-age children.

PMID- 22374563
TI  - Risk of asthma associated with energy-dense but nutrient-poor dietary pattern in
      Taiwanese children.
AB  - Childhood asthma has rapidly increased over the past few decades, possibly due to
      changes in lifestyle and dietary patterns. We aimed to determine associations
      between dietary patterns and asthma in schoolchildren in Taiwan. The Nutrition
      and Health survey in Taiwan Elementary School Children was carried out by using a
      multi-staged complex sampling design. A total of 2,082 elementary school children
      with complete data on dietary, lifestyle, demographics and asthma were included
      in the analysis. We used a Chinese version of the International Study of Asthma
      and Allergies in Childhood questionnaire to generate an asthma symptom score and
      to define asthma outcomes. Dietary intake was assessed by a food frequency
      questionnaire. Reduced rank regression (RRR) was used to identify the dietary
      pattern associated with the asthma symptoms score. Asthma outcomes included;
      current asthma, current severe asthma, nocturnal cough, exercise-induced wheeze
      and asthma ever. The RRR-derived dietary pattern was characterized by high
      consumption of fast foods, high-fat snacks, candy, and cheese; and low
      consumption of fruit, vegetables and rice. The RRR-derived dietary pattern was
      associated with an increased risk of current asthma (OR [95% CI]) (2.42 [1.19
      4.93] for Q4/Q1, p-for-trend=0.01), current severe asthma (3.21 [1.11-9.25] for
      Q3/Q1, 4.45 [1.59-12.5] for Q4/Q1; p-for-trend=0.003), and nocturnal cough (1.79
      [1.06-3.05] for Q2/Q1, 1.74 [1.02-2.97] for Q3/Q1, 1.82 [1.07-3.11] for Q4/Q1; p
      for-trend=0.049). Our results suggest that a diet with a high intake of fat and
      simple sugars and low intake of fruit, vegetables and rice is associated with an
      increased risk of asthma in Taiwanese children.

PMID- 22374564
TI  - Associations of the pre-pregnancy body mass index and gestational weight gain
      with pregnancy outcomes in Taiwanese women.
AB  - BACKGROUND: Pre-pregnancy weight and gestational weight gain (GWG) are important
      factors in both maternal and infant outcomes. Little information is available in
      relation to different levels of pre-pregnancy body mass index (BMI) and body
      weight gain on obstetric outcomes in Taiwan. This study investigated the
      associations between pregnancy complications with pre-pregnant BMI and GWG, in
      Taiwanese women. METHODS: Data were extracted from a delivery room information
      bank on all women delivering singleton babies in a medical center. Eight hundred
      and sixty pregnant women were included. The collected variables included basic
      information, GWG, and pregnancy and neonatal outcomes. Pregnant women were
      categorized according to their pre-pregnant BMI and GWG to evaluate the impacts
      of pre-pregnant BMI and maternal weight gain on the risk of pregnancy
      complications. Univariate and multivariable logistic regression analyses were
      performed, and odds ratios were calculated. RESULTS: Pre-pregnancy BMI>=24 kg/m2
      increased the risks of gestational diabetes mellitus, preeclampsia, and preterm
      labor. Preeclampsia and Cesarean delivery were positively associated with high
      weight gains (>18 kg), whereas a low birth weight and preterm labor were strongly
      associated with low weight gains (<10 kg). A higher birth weight was found with a
      GWG of >14 kg in women who were underweight and normal weight before pregnancy.
      CONCLUSION: An appropriate maternal BMI (18.5-24 kg/m2) at conception followed by
      a suitable gestational weight gain (10-14 kg) has substantial impact on the
      overall health of pregnant women and would lead to better obstetric management
      for Taiwanese women.

PMID- 22374565
TI  - Continuous metabolic syndrome risk score for predicting cardiovascular disease in
      the Chinese population.
AB  - Although the metabolic syndrome (MetS) is a predictor of cardiovascular disease
      (CVD), the current dichotomous definition of MetS cannot be used to evaluate
      context-specific identification or for efforts to reduce the risk of CVD in the
      population. In this study, we assigned MetS a continuous risk score for
      predicting the development of CVD. In total, 3,598 participants recruited from
      the Jiangsu Province of China were followed for a median of 6.3 years. A total of
      82 participants developed CVD during the follow-up period. Receiver operating
      characteristic (ROC) curve was used to analyze the association between components
      of MetS and CVD. The results show that systolic blood pressure (SBP) was
      associated with CVD more intimately (area under receiver-operator characteristic
      curve (AUC)=0.72, 95% confidence interval (CI), 0.66-0.77) than other features of
      MetS. When each MetS component was assigned according to the magnitude of
      regression coefficients in the Cox regression hazard model, the AUC of the
      continuous MetS risk score (AUC=0.80, 95% CI, 0.75-0.84) exceeded that of the
      dichotomized definition of MetS (AUC=0.63, 95% CI, 0.56-0.69) (p<0.01). The
      incidence of CVD increased with the MetS risk score. This prospective cohort
      study suggests that the use of continuous MetS risk score would significantly
      improve the capability for predicting the development of CVD compared to current
      definition of MetS. Further, the appropriate cut-off points need to be verified
      in other races and regions.

PMID- 22374566
TI  - Validity and reproducibility of a food frequency questionnaire (FFQ) for dietary
      assessment in Malay adolescents in Malaysia.
AB  - BACKGROUND: Food frequency questionnaire (FFQ) must be tailored to the target
      populations because dietary habits vary within the populations due to differences
      in cultural and lifestyles practices. Limited information is available to assess
      the validity of FFQ used among Malaysian adolescents. OBJECTIVE: To construct the
      validity and reproducibility of a newly developed FFQ in assessing habitual
      nutrients intake over the past year of 170 Malay adolescent boys and girls in
      Kelantan, Malaysia. METHODS: The FFQ that consisted of 124 food items was
      assessed, whereas three days of 24-hours dietary recalls (DR) was administered as
      the standard criteria method. RESULTS: Estimated mean intake for most nutrients
      assessed by the FFQ were higher as compared to the three DRs (p<0.05). Pearson
      correlation coefficients for energy-adjusted nutrients intake between both
      methods were ranged from 0.22 (zinc) to 0.68 (calcium) with a median r-value of
      0.43. The cross classification of quartile analysis showed that most nutrients
      were classified into the same or adjacent quartiles (median=52.7%). For the
      reproducibility of FFQ, the correlation of nutrients ranged from 0.43 for
      carotene to 0.86 for total fat intake (median=0.67), after adjusting for total
      energy intake. CONCLUSION: The newly developed dietary FFQ is a relatively good
      and valid tool in assessing habitual nutrients intake for the past year among
      Malay adolescents in Malaysia.

PMID- 22374567
TI  - Symposium on nutrition and cognition: towards research and application for
      different life stages.
AB  - A SYMPOSIUM ON NUTRITION AND COGNITION: Towards research and application for
      different life stages was held on October 2010 in Malaysia. The influence of diet
      and nutrition on the cognitive development of the child and on cognitive decline
      in later life was reviewed. Central to the study of such topics is the assessment
      of cognitive functioning. Cognitive functioning falls into six main areas:
      executive functioning, memory, attention, perception, psychomotor and language
      skills, although each domain can be further subdivided. As it is in the nature of
      human functioning that the performance on any cognitive test can reflect aspects
      of many of these domains, ideally a battery of tests should be used to establish
      the basis of any difference in performance. In intervention studies, frequently
      there has been a failure to demonstrate a beneficial influence of changes in
      diet. A possible reason is that studies have failed to acknowledge the time scale
      and critical ages over which diet has an impact. Diet may have a slow and
      progressive influence making it difficult for short-term studies to show an
      improvement. In addition, as many factors influence human behaviour, dietary
      interventions should only be one part of a coordinated approach; the effect of
      diet will depend on the social and psychological context in which an individual
      lives. Placing diet into a broader social and psychological context greatly
      increases the chance of generating significant findings. This report highlights
      and reviews presentations and discussions at the symposium.

PMID- 22374568
TI  - Present status and issues of school nutrition programs in Korea.
AB  - School nutrition programs are essential for children's long-term nutrition and
      health promotion. The last decade has been the most dramatic years in the history
      of school nutrition programs in Korea. The percentage of schools serving school
      lunches reached almost 100% in 2003. In 2006, School Meals Act was significantly
      revised after serial outbreaks of food-borne illness among students having eaten
      school lunches. The safety and nutritional quality of school meals had remained
      as the biggest issue until the middle of 2000s, and then eco-friendly and
      universal free school lunches have become the main issues related to school meal
      service and are still under debate. Implementation of the Nutrition Teacher
      System in 2006 was the turning point of school-based nutrition education in
      Korea. In addition, two new laws, Special Act on Children's Dietary Life Safety
      Management of 2008 and Dietary Life Education Support Act of 2009, started to
      make meaningful changes in school nutrition environment and practices. The next
      decade is expected to be very critical in the development of school nutrition
      programs in Korea as the new systems and laws are to be settled. Significant
      effort is needed from both the academia and the field to make the related issues
      to be debated and answered to progressive direction for the school nutrition
      programs in Korea.

PMID- 22374569
TI  - The practices and needs of dietitian in school lunch program in Taiwan.
AB  - Nutrition-related problems among school-age children nowadays become potentially
      serious. In order to prevent obesity and other nutritionally related diseases in
      the young generation, a school lunch program has been proposed and conducted in
      Taiwan. It is to ensure that students' nutritional intake meets the daily
      requirement and to help students develop correct eating habits and maintain a
      healthy lifestyle. A professional dietitian who has a clear concept regarding
      food material utilization, cooking methods and nutritional values thus becomes
      important. However, the majority of schools in Taiwan are unable to offer the
      post of dietitian due to budgetary constraints and lack of organization. The
      responsibility of a dietitian is usually held by teachers, school nurses and
      other administrative staff. This problem has hindered the nutritional education
      in schools and made school lunches less beneficial to the children's nutritional
      needs. For the current status of dietitians in schools, a large gap is found
      between the currently supplied school lunches and the nutritionally standardized
      school lunches. It also exists in relation to education and hygiene. One of the
      solutions requires an infrastructure to support plans and policy, reasonable
      adequate budget, well human affairs establishment and coordination of all
      aspects. While the needed infrastructure is being proposed, an access to the
      professionalism of the currently employed dietitians can be strategically
      explored by constructing an education system. Through the system, schools without
      on-campus dietitians will be able to utilize their expertise with which the
      improvement of school lunches can be expectedly accomplished.

PMID- 22374570
TI  - School meal program in Ho Chi Minh city, Vietnam: reality and future plan.
AB  - The socio-economic status in Vietnam has developed during the past decades.
      People become busier for work, and thus they do not have enough time to prepare
      meal for their children. The school meal program, organized by Department of
      Education, was first implemented at a kindergarten in 1977, which has been
      extended to elementary school since 1980. Up to date, 100% of kindergarten and
      approximately 90% of elementary schools have school meal programs. The purposes
      of this program are to provide appropriate meals for students, and to serve as
      education and communication tool for students. About 90% of school meals are
      prepared in the school's kitchen and the rest are provided by food companies. The
      weekly menu provides approximately 30% of recommended dietary allowances (RDA)
      for students. To date, there has been is no official dietitian training school in
      Vietnam. The head of school kitchen, who is not dietitian, is required to
      participate in a short-term training course, where s/he learns basic nutrition,
      nutrition requirements and food hygiene and safety. The food companies, which
      provide meals to school, must be approved for the hygiene and safety condition by
      the Human Health Services Department of Ho Chi Minh City. In the next plan of
      national nutrition strategy, establishing dietitian training schools will be
      prioritized. In addition, the regular nutritional surveillance for school-aged
      students will be introduced in school system thus we can develop and evaluate the
      school meal program in terms of nutrients, food safety and nutrition education.

PMID- 22374571
TI  - Nurturing healthy dietary habits among children and youth in Singapore.
AB  - Healthy diet is a key tenet in the prevention of many chronic diseases. Nurturing
      healthy dietary habits is especially important in childhood as this is a critical
      period of growth and development. Furthermore, dietary habits are shaped from an
      early age with many of them forming even below the age of 5 years. Therefore, the
      importance of nurturing healthy dietary habits during a child's formative years
      cannot be underestimated. Reducing fat, salt and sugar intake and at the same
      time, advocating the consumption of adequate whole-grains, fruit and vegetables
      among the population remain the cornerstone of the Singapore Health Promotion
      Board's (HPB) key nutrition initiatives. To achieve this, HPB adopts a multi
      pronged approach comprising various strategies to promote healthy eating among
      children and youth in Singapore. This article provides an overview of these
      strategies and the broad range of nutrition education efforts targeted at the
      young.

PMID- 22374572
TI  - School lunch program in India: background, objectives and components.
AB  - The School Lunch Program in India (SLP) is the largest food and nutrition
      assistance program feeding millions of children every day. This paper provides a
      review of the background information on the SLP in India earlier known as
      national program for nutrition support to primary education (NP-NSPE) and later
      as mid day meal scheme, including historical trends and objectives and
      components/characteristics of the scheme. It also addresses steps being taken to
      meet challenges being faced by the administrators of the program in monitoring
      and evaluation of the program. This program was initially started in 1960 in few
      states to overcome the complex problems malnutrition and illiteracy. Mid Day Meal
      Scheme is the popular name for school meal program. In 2001, as per the supreme
      court orders, it became mandatory to give a mid day meal to all primary and later
      extended to upper primary school children studying in the government and
      government aided schools. This scheme benefitted 140 million children in
      government assisted schools across India in 2008, strengthening child nutrition
      and literacy. In a country with a large percent of illiterate population with a
      high percent of children unable to read or write; governmental and non
      governmental organizations have reported that mid day meal scheme has
      consistently increased enrollment in schools in India. One of the main goals of
      school lunch program is to promote the health and well-being of the Nation's
      children.

PMID- 22374573
TI  - School lunch program for health promotion among children in Japan.
AB  - In Japan, the present school lunch program has been implemented under the "School
      Lunch Act" enacted in 1954. The main purpose of the school lunch program is to
      promote healthy development of the minds and bodies of school children. Later,
      "The School Lunch Act" was revised in 2008 and its aim was changed to "promoting
      Shokuiku". As of May 2009, approximately 10 million school children participate
      in the school lunch program. This program itself is an educational activity.
      School children are responsible for serving lunch and clearing the dishes. They
      could also learn proper manners, by having meals together with classmates.
      Furthermore, understanding of balanced diet and food culture can be enhanced
      through learning the menu of each meal. Recently, as eating disorders and obesity
      increase among adults and school children, there is rising concern on development
      of lifestyle-related diseases. Under this circumstance, the Basic Law on Shokuiku
      was enacted in 2005. Besides, in order to enhance Shokuiku to school children,
      the Ministry of Education, Culture, Sports, Science and Technology established
      the Diet and Nutrition Teacher System in April 2007. It is reported that, in
      those schools with Diet and Nutrition Teachers, a positive impact has been
      observed in terms of awareness and interest in diet among teachers and guardians.
      It is also reported that proportion of children skipping breakfast has decreased,
      and quality of life has been improved. In this way, the Japanese school lunch
      program system is essential for fostering healthy mind and bodies for the next
      generation.

PMID- 22374574
TI  - School-based "Shokuiku" program in Japan: application to nutrition education in
      Asian countries.
AB  - This paper provides the overview of "Shokuiku" in Japan, and discusses the future
      perspective on application of its concepts to nutrition education in other Asian
      countries. In Japan, there has been a growing concern on increase of obesity and
      the metabolic syndrome among middle-aged men. Additionally, child obesity has
      also become one of the important health problems. The increased obesity among
      them is possibly associated with inappropriate dietary habits (eg skipping
      breakfast, excessive fat intake and insufficient vegetable). Under this
      circumstance, the "Basic Law on Shokuiku" was enacted in 2005, which was the
      first law that regulates one's diets and eating habits. For effective
      implementation of Shokuiku program, dietitians and registered dietitians would
      play important roles in various settings. Japan has a long history of dietitian
      system as well as school-lunch programs. Later, in order to further enhance the
      school-based Shokuiku programs, the Diet and Nutrition Teacher System was
      established in April 2007. From an international point of view, "nutrition
      education" programs aim to improve dietary practices so as to ensure adequate
      energy or nutrient intake and also to reduce obesity and lifestyle-related
      diseases, whereas the concepts of Shokuiku have very wide approaches. Shokuiku's
      efforts expand to support food culture, especially through school-based programs,
      as well as to improve food environment by providing information on appropriate
      diets. These approaches can be introduced in nutrition education in other Asian
      countries, not only to improve one's health and nutritional status but also to
      secure food culture and food safety in each country.

PMID- 22374575
TI  - Solvation of Na+, K+, and their dimers in helium.
AB  - Helium atoms bind strongly to alkali cations which, when embedded in liquid
      helium, form so-called snowballs. Calculations suggest that helium atoms in the
      first solvation layer of these snowballs form rigid structures and that their
      number (n) is well defined, especially for the lighter alkalis. However,
      experiments have so far failed to accurately determine values of n. We present
      high-resolution mass spectra of Na(+)He(n), K(+)He(n), Na(2)(+)He(n) and
      K(2)(+)He(n), formed by electron ionization of doped helium droplets; the data
      allow for a critical comparison with several theoretical studies. For sodium and
      potassium monomers the spectra indicate that the value of n is slightly smaller
      than calculated. Na(2)(+)He(n) displays two distinct anomalies at n=2 and n=6, in
      agreement with theory; dissociation energies derived from experiment closely
      track theoretical values. K(2)(+)He(n) distributions are fairly featureless,
      which also agrees with predictions.

PMID- 22374576
TI  - Nodules in antrum after variceal eradication a new finding in patients with
      portal hypertension.
AB  - Portal hypertension is known to cause esophageal varices, gastric varices and
      portal hypertensive gastropathy (PHG). The prevalence of gastric varices and PHG
      is known to increase after eradication of esophageal varices. PHG includes the
      presence of a mucosal mosaic pattern, cherry red spots, and/or black-brown spots
      and gastric vascular ectasia (GAVE). Patients with portal hypertension in whom
      esophageal varices were eradicated were on follow up endoscopy for detection of
      recurrence of esophageal varices. Their status of PHG was assessed and patients
      antral nodules were enrolled. Twenty patients with antral nodules were identified
      over one year. Fifteen out of 20 patients had cirrhosis as etiology of portal
      hypertension, three had non-cirrhotic portal hypertension and two had extra
      hepatic portal vein thrombosis. GAVE was seen more commonly (n=8, 40%) in
      patients with PHG with nodules. PHG with antral nodules is a novel endoscopic
      finding present both in cirrhotic and non-cirrhotic portal hypertension with
      unknown pathogenesis, and is seen more commonly in patients with eradicated
      varices who are on long-term follow up.

PMID- 22374577
TI  - Neuroanesthesia: from bench to bed.
AB  - It has been over 40 years since the term "neuroanesthesia" emerged. The
      anesthesiologists specializing in neuroanesthesia have actively conducted basic
      research on cerebral ischemia as well as on cerebral blood flow and metabolism.
      However, translating the results of basic research using experimental animals
      into clinical applications has been often unsuccessful, especially in the area of
      cerebral ischemia. The negative results produced by a series of hugely costly and
      time-consuming collaborative multicenter trials have disappointed many
      researchers. It could be argued that discrepancies in the efficacy of an agent
      ought to be viewed in the context of the differences between experimental animals
      and humans since they have considerably different higher-order functions, and
      consequently the relevance of using experimental animals is brought into
      question. Nevertheless, the accuracy of basic research can be improved by taking
      measures to reduce bias. Taking such measures may enable more careful judgments
      to be made at the basic research stage and prevent unnecessary clinical studies.
      Although it could be seen as taking a slight detour, it is advisable to create a
      system that facilitates confirmation of the original findings by a multicenter
      basic research project before starting a collaborative multicenter clinical
      trial.

PMID- 22374578
TI  - Solvent-free luminescent organic liquids.
AB  - Illuminating! Isolation of a pi-core by covalently attached flexible hydrocarbon
      chains has been employed to synthesize blue-emitting oligo(p-phenylenevinylene)
      (OPV) liquids with tunable viscosity and optical properties. A solvent-free,
      stable, white-light emitting ink/paint, which can be applied onto various
      surfaces and even onto LEDs, was made by blending of liquid OPVs with emissive
      solid dopants.

PMID- 22374579
TI  - Quantitative investigations of quantum coherence for a light-harvesting protein
      at conditions simulating photosynthesis.
AB  - Recent measurements using two-dimensional electronic spectroscopy (2D ES) have
      shown that the initial dynamic response of photosynthetic proteins can involve
      quantum coherence. We show how electronic coherence can be differentiated from
      vibrational coherence in 2D ES. On that basis we conclude that both electronic
      and vibrational coherences are observed in the phycobiliprotein light-harvesting
      complex PC645 from Chroomonas sp. CCMP270 at ambient temperature. These light
      harvesting antenna proteins of the cryptophyte algae are suspended in the lumen,
      where the pH drops significantly under sustained illumination by sunlight. Here
      we measured 2D ES of PC645 at increasing levels of acidity to determine if the
      change in pH affects the quantum coherence; quantitative analysis reveals that
      the dynamics are insensitive to the pH change.

PMID- 22374580
TI  - Polymorphisms in second intron of the FGFR2 gene are associated with the risk of
      early-onset breast cancer in Chinese Han women.
AB  - Fibroblast growth factor receptor 2 (FGFR2) plays an important role in tumor cell
      growth, invasiveness, motility, and angiogenesis. Several single-nucleotide
      polymorphisms (SNPs) in the second intron of the FGFR2 gene are associated with
      the risk of breast cancer. In this study, we determined whether these SNPs of the
      FGFR2 gene are associated with early onset of non-familial breast cancer in a
      Chinese Han population. Recruited were 118 female breast cancer patients who were
      less than or equal to 35 years of age and without a family history of breast
      cancer, and 104 age-matched healthy controls. Six SNPs of the second intron of
      the FGFR2 gene, including rs2981428C/A (i.e., a change at this particular site
      from nucleotide C to A), rs11200014G/A, rs2981579C/T, rs1219648A/G, rs2420946C/T,
      and rs2981582C/T, were detected using matrix-assisted laser desorption/ionization
      mass spectrometry. The data showed that the homozygotes at each minor allele,
      rs11200014 (AA), rs1219648 (GG), rs2420946 (TT), and rs2981582 (TT), were
      significantly associated with an increased risk of early-onset non-familial
      breast cancer. The haplotype containing rs11200014A, rs1219648G, rs2420946T and
      rs2981582T also exhibited a significantly higher distribution in patients
      compared to controls (OR=1.784, 95% CI=1.161-2.744). In stratified analyses, each
      of the above four SNPs conferred a significantly greater risk of estrogen
      receptor-positive breast cancer, compared to estrogen receptor-negative breast
      cancer that is more resistant to treatment. Our data demonstrate that these four
      SNPs of the FGFR2 gene are associated with the risk of breast cancer at a young
      age in Chinese Han women.

PMID- 22374581
TI  - Helix and hairpin nucleation in short peptides using centrally positioned
      conformationally constrained dipeptide segments.
AB  - The effect of incorporation of a centrally positioned Ac(6)c-Xxx segment where
      Xxx = (L)Val/(D)Val into a host oligopeptide composed of l-amino acid residues
      has been investigated. Studies of four designed octapeptides Boc-Leu-Phe-Val
      Ac(6)c-Xxx-Leu-Phe-Val-OMe (Xxx = (D)Val 1, (L)Val 2) Boc-Leu-Val-Val-Ac(6)c-Xxx
      Leu-Val-Val-OMe (Xxx = (D)Val 3, (L)Val 4) are reported. Diagnostic nuclear
      Overhouse effects characteristic of hairpin conformations are observed for Xxx =
      (D)Val peptides (1 and 3) while continuous helical conformation characterized by
      sequential N(i)H <-> N(i+1)H NOEs are favored for Xxx = (L)Val peptides (2 and 4)
      in methanol solutions. Temperature co-efficient of NH chemical shifts are in
      agreement with distinctly different conformational preferences upon changing the
      configuration of the residue at position 5. Crystal structures of peptides 2 and
      4 (Xxx = (L)Val) establish helical conformations in the solid state, in agreement
      with the structures deduced from NMR data. The results support the design
      principle that centrally positioned type I beta-turns may be used to nucleate
      helices in short peptides, while type I'beta-turns can facilitate folding into
      beta-hairpins.

PMID- 22374582
TI  - Exposure to second-hand smoke at home and its associated factors: findings from
      the Global Adult Tobacco Use survey in Vietnam, 2010.
AB  - OBJECTIVE: The paper describes the pattern of exposure to second-hand smoke (SHS)
      at home among the adult population of Vietnam and examines associated socio
      demographic factors. METHODS: A total of 11,142 households were selected for this
      survey using a two-phase sampling design analogous with three-stage stratified
      cluster sampling. The dependent variable was the status of exposure to SHS at
      home. Independent variables included gender, age, occupation, asset-based wealth
      quintile, ethnicity, marital status, residence. Logistic regression modelling was
      performed to examine the association with relevant factors of patterns of
      exposure to second-hand smoke among non-smokers. RESULTS: Of adults aged 15 years
      and above (representing approximately 47 million people) 73.1% reported they were
      exposed to SHS at home at least monthly. Considering non-smokers only, the
      prevalence of exposure to SHS at home was 67.6% (equivalent to approximately 33
      million non-smokers). The significant correlates of the status of exposure to SHS
      at home among non-smokers were female gender, ethnic minority, low education, and
      lack of smoking restriction at home. CONCLUSION: The study showed that a high
      percentage of people are exposed to second-hand smoke at home. Disadvantaged
      people were more likely than the better-off to be exposed to SHS at home.

PMID- 22374583
TI  - Thoracoscopic anatomy and approaches of the anterior thoracic spine: cadaver
      study.
AB  - PURPOSE: [corrected] In spite of the extensive case studies considering
      thoracoscopic approaches to the anterior thoracic spine, the literature lacks
      studies of the thoracoscopic anatomic dissection and approaches. In this article,
      the authors present their study of thoracoscopic anatomy of the anterior spine
      with illustrated step-wise dissection and approaches for sympathectomy,
      discectomy and corpectomy. MATERIALS AND METHODS: Four adult cadavers with no
      history of disease, local trauma or surgery were studied and bilateral
      thoracoscopic anterior spinal approaches were performed. Thoracoscopic
      dissections were done in the Department of Anatomy, using Karl Storz 30 degrees ,
      5 mm and 30 cm rod lens rigid endoscope (Karl Storz and Co., Tuttlingen,
      Germany). As surgical instrumentation, Karl Storz Rosenthal endoscopic surgical
      set and 15 mm portals were used for all approaches. RESULTS: For sympathectomy,
      the cadaver is positioned supine and the port locations are in the third and
      fifth intercostal spaces in the anterior axillary line. The stellate ganglion is
      cephalad to the second rib, and the T2 and T3 ganglia are divided just superior
      to T2 ganglia and inferior to T3. For discectomy, the cadaver is positioned in
      the lateral decubitus position. The working portal is positioned directly over
      the affected disc in the posterior axillary line. The camera portal is positioned
      in the middle axillary line; 2-3 intercostal spaces caudal to the working portal.
      The rib head is removed and the lateral surface of the pedicle and neural foramen
      are exposed. The pedicle and the floor of the spinal canal are resected to
      decompress the ventral aspect of the spinal canal. For corpectomy, the position
      of the cadaver and ports are as same as for discectomy. The adjacent segmental
      vessels are divided first, and the discs above and below the targeted corpus are
      removed. The ipsilateral pedicle is then removed to decompress the anterior
      spinal cord, followed by median corpectomy. CONCLUSIONS: Thoracoscopic approaches
      are minimally invasive procedures and they can be used safely in patients who
      need anterior exposure to the thoracic spine for the treatment of a spectrum of
      diseases. Knowledge of the normal anatomy and thoracoscopic cadaver dissection
      are essential steps in improving the learning curve.

PMID- 22374584
TI  - A Bayesian approach to the statistical analysis of device preference studies.
AB  - Drug delivery devices are required to have excellent technical specifications to
      deliver drugs accurately, and in addition, the devices should provide a
      satisfactory experience to patients because this can have a direct effect on drug
      compliance. To compare patients' experience with two devices, cross-over studies
      with patient-reported outcomes (PRO) as response variables are often used.
      Because of the strength of cross-over designs, each subject can directly compare
      the two devices by using the PRO variables, and variables indicating preference
      (preferring A, preferring B, or no preference) can be easily derived.
      Traditionally, methods based on frequentist statistics can be used to analyze
      such preference data, but there are some limitations for the frequentist methods.
      Recently, Bayesian methods are considered an acceptable method by the US Food and
      Drug Administration to design and analyze device studies. In this paper, we
      propose a Bayesian statistical method to analyze the data from preference trials.
      We demonstrate that the new Bayesian estimator enjoys some optimal properties
      versus the frequentist estimator.

PMID- 22374585
TI  - When independent healthcare behaviors develop in adolescents with inflammatory
      bowel disease.
AB  - BACKGROUND: Patients with chronic health needs are expected to gradually assume
      responsibility for health maintenance behavior as they move toward adulthood. We
      sought to evaluate the influence of factors such as age, duration of disease, and
      gender by examining the self-reported health behaviors of adolescents with
      inflammatory bowel disease (IBD). METHODS: Confidential voluntary surveys were
      administered to all IBD outpatients over age 10 during a 4-month period.
      Questions addressed responsibility for health behaviors such as medication,
      provider visits, and communication. Likert scales measured the degree of
      independence: 1 (my parents only) through 3 (parents share equally with me) to 5
      (I do it myself). Patient participation during doctor visits was also assessed.
      RESULTS: Of 358 patients approached, 294 (82%) returned completed surveys.
      Respondents were 51% male and 69% had Crohn's disease. Patients took increasingly
      active roles, but by ages 19-21 only 45% ordered medication refills, and 50%
      picked up medication from pharmacy. Only 35% of 19-21-year-olds scheduled
      appointments and 30% contacted providers between visits if problems arose. Most
      patients could answer provider questions (55% at age 16-18) but fewer asked
      questions of the provider (15% at the same age). Males were less likely to order
      their own prescription refills (P = 0.017) or prepare questions (P = 0.009).
      Duration of disease did not change skill acquisition. CONCLUSIONS: Adolescents
      develop independence in managing their IBD slowly and many patients >= 18 years
      are still assisted by parents. Focus on specific skill acquisition may help
      patients with self-management skills expected in adult healthcare.

PMID- 22374588
TI  - Proacetylenic reactivity of a push-pull buta-1,2,3-triene: new chromophores and
      supramolecular systems.

PMID- 22374587
TI  - Effect of Rebaudioside A, a diterpenoid on glucose homeostasis in STZ-induced
      diabetic rats.
AB  - Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently
      proposed as an insulinotropic agent. The aim of this investigation was to
      evaluate the antihyperglycemic effect of Reb A on the activities of hepatic
      enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats.
      Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a
      single intraperitoneal injection at a dose of STZ (40 mg/kg body weight).
      Diabetic rats showed significant (P<0.05) increase in the levels of plasma
      glucose and glycosylated hemoglobin and significant (P<0.05) decrease in the
      levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such
      as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly
      (P<0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were
      significantly (P<0.05) decreased in the liver along with glycogen. Oral treatment
      with Reb A to diabetic rats significantly (P<0.05) decreased blood glucose and
      reversed these hepatic carbohydrate metabolizing enzymes in a significant manner.
      Histopathology changes of pancreas confirmed the protective effects of Reb A in
      diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic
      activity and provide evidence for its traditional usage in the control of
      diabetes.

PMID- 22374589
TI  - Developing health promotion interventions on social networking sites:
      recommendations from The FaceSpace Project.
AB  - Online social networking sites offer a novel setting for the delivery of health
      promotion interventions due to their potential to reach a large population and
      the possibility for two-way engagement. However, few have attempted to host
      interventions on these sites, or to use the range of interactive functions
      available to enhance the delivery of health-related messages. This paper presents
      lessons learnt from "The FaceSpace Project", a sexual health promotion
      intervention using social networking sites targeting two key at-risk groups.
      Based on our experience, we make recommendations for developing and implementing
      health promotion interventions on these sites. Elements crucial for developing
      interventions include establishing a multidisciplinary team, allowing adequate
      time for obtaining approvals, securing sufficient resources for building and
      maintaining an online presence, and developing an integrated process and impact
      evaluation framework. With two-way interaction an important and novel feature of
      health promotion interventions in this medium, we also present strategies
      trialled to generate interest and engagement in our intervention. Social
      networking sites are now an established part of the online environment; our
      experience in developing and implementing a health promotion intervention using
      this medium are of direct relevance and utility for all health organizations
      creating a presence in this new environment.

PMID- 22374590
TI  - [Predictor of intrathoracic lymph node metastasis in peripheral non-small cell
      lung cancers 20 mm or less in greatest dimension].
AB  - PURPOSES: To assess the independent predictor of lymph node metastasis( LNM) in
      peripheral smallsized non-small cell lung cancers (NSCLCs), we conducted a
      clinicopathologic analysis of patients with small-sized NSCLCs with and without
      intrathoracic LNM. METHODS: We retrospectively studied 213 patients who had
      undergone surgical resection of NSCLCs 20 mm or less in diameter. Categories of
      patient characteristics were divided into 2 groups based on clinicopathologic
      features, and the incidence of LNM was compared. Univariate and multivariate
      analyses of factors affecting overall survival( OS) were also conducted. RESULTS:
      In pN1-2 group (n=19), the incidence of elevated (>5 ng/dl) of preoperative
      carcinoembryonic antigen (CEA) and larger tumor size (>10 mm) was significantly
      higher than that in pN0 group (n=194) [p=0.0004, 0.0025]. Preoperatively, 73.7%
      patients were diagnosed as having lower stage in N-staging. Multivariate analysis
      identified only pN staging as an independent prognostic factor (p=0.002).
      CONCLUSIONS: It is likely that preoperative CEA and tumor size are useful in
      selecting patients with micro-N1-2 disease among those with small-sized NSCLCs.
      Our results indicate that limited resection should be avoided in patients with
      elevated CEA or tumors more than 10 mm in size, even if preoperative radiographic
      findings suggest no intrathoracic LNM.

PMID- 22374591
TI  - [Ascending aorta cannulation in stanford type a acute aortic dissection].
AB  - Establishment of cardiopulmonary bypass for Stanford type A acute aortic
      dissection( type A AAD) should be quick and safe. The femoral artery, axillary
      artery, ascending aorta, and left ventricular apex are potential access points
      for cannulation. The most important reason for establishing cardiopulmonary
      bypass for type A AAD is to allow antegrade blood flow through the true lumen.
      Starting in 2007, Jakob et al, and Inoue et al. applied the technique of
      ascending aortic cannulation for type A AAD. From 2008, we applied this method of
      ascending aorta cannulation in 8 patients and compared preoperative, operative,
      and postoperative data with a control group, or the femoral artery cannulation
      group. Ascending aorta cannulation was done safely and easily with the use of the
      Seldinger technique under epiaortic color Doppler echography and  transesophageal
      echography. No cerebral events or hypoperfusion-based complications occurred in
      the group of ascending aorta cannulation. Given that no cases of complication
      occurred using this method, it could be considered as an effective choice of
      cannulation for cardiopulmonary bypass.

PMID- 22374586
TI  - Regulation of 17beta-hydroxysteroid dehydrogenases in cancer: regulating steroid
      receptor at pre-receptor stage.
AB  - Increased intracelullar hormone concentration levels have been shown to be the
      cause of several endocrine-related cancers including breast, prostate,
      endometrial, ovarian, cervix, testicular, thyroid, and osteosarcoma. Deregulated
      expression of steroidogenic enzymes in these tumors seems to be the source of a
      positive balance in active steroids that bind to the corresponding nuclear
      receptor, thus ultimately stimulating cell proliferation. Among these enzymes,
      17beta-hydroxysteroid dehydrogenases catalyze the interconversion between 17
      ketosteroids and 17-hydroxysteroids on the last steps of sex hormones
      biosynthesis and metabolism. To date, 14 isoforms have been identified in
      vertebrates although only 13 are present in humans. Development and clinical
      evaluation of specific inhibitors to block their activity is currently under
      progress especially against the best characterized members 1 to 5. Selectivity
      and potency of these drugs constitute the main challenge in this new approach to
      cancer and steroid-dependent diseases treatment at the "pre-receptor level". Here
      we review the current state of knowledge regarding the deregulation of the
      expression of some of these enzymes in endocrine-related tumors.

PMID- 22374592
TI  - [Investigation of rescued cases with cardiac rupture caused by blunt trauma].
AB  - The mortality of cardiac rupture by blunt trauma is so high that quick diagnosis
      and appropriate treatment are essential for saving patients. Based on 8 such
      cases rescued in our hospital and on 70 other rescued cases reported in Japan, we
      review its treatment strategy. Ultrasound examination, particularly focused
      assessment with sonography for trauma (FAST), was useful for diagnosing traumatic
      cardiac rupture. It was, however, impossible to detect the exact site of rupture
      before surgery. Three quarters of the rescued cases suffered from right cardiac
      rupture and more than 95% of those were treated successfully without
      extracorporeal circulation. All the cases with multiple cardiac rupture needed
      cardiopulmonary bypass or percutaneous cardiopulmonary support (PCPS) for their
      surgeries. And so did a quarter of the cases with left cardiac rupture. The
      standard treatment strategy seems to be as follows:to release cardiac tamponade
      as slowly as possible, to set up an extracorporeal circulation for surgery, and
      to repair the ruptured heart via median sternotomy.

PMID- 22374593
TI  - [Left ventricular outflow tract pseudoaneurysm complicated with prosthetic valve
      endocarditis after aortic valve replacement].
AB  - A rare case of left ventricular outflow tract (LVOT) pseudoaneurysm complicated
      with prosthetic valve endocarditis was reported herein. A 78-year-old male
      previously underwent aortic valve replacement (AVR) with a bioprosthesis. Four
      years after the initial operation, he presented with prolonged high fever and
      bloody sputum. Multi-detector row computed tomography (MDCT) clearly showed LVOT
      pseudoaneurysm originating from a subvalvular fibrous region. The patient
      underwent re-AVR and repair of pseudoaneurysm. The postoperative course was
      uneventful, and the patient recovered good condition.

PMID- 22374594
TI  - [Air embolism at the pleurodesis for air leakage after pulmonary resection].
AB  - A 61-year-old female who was diagnosed with right lung cancer had right lower
      lobectomy by videoassisted thoracic surgery in June 2010. At the 7th post
      operative day( 7POD), the patient complained of dyspnea and chest X-ray showed
      right pneumothorax which was successfully treated by closed drainage and
      pleurodesis. Since then repeated right pneumothorax appeared and the same
      procedures were chosen for treatment. In September 2010, just after the
      pleurodesis for the 3rd time event, she lost consciousness. Brain computed
      tomography (CT) demonstrated air density area in bilateral internal carotid
      arteries and right parietal lobe, establishing the diagnosis of air embolism
      which was successfully treated by hyperbaric oxygen treatment.

PMID- 22374595
TI  - [Multilocular thymic cyst associated with rheumatoid arthritis].
AB  - A 66-year-old woman had been receiving treatment for rheumatoid arthritis( RA)
      since her 28 years of age. Chest computed tomography( CT) taken during follow-up
      showed an anterior mediastinal tumor of 35*20*65 mm in size as a region of
      heterogeneous internal density. Accumulation of 18F-fluorodeoxyglu cose was
      identified on positron emission tomography( PET)[ maximum standardized uptake
      value( SUV max) 8.7]. Thymic epithelial tumor( thymoma or thymic cancer) with
      cystic degeneration was initially suspected, so total thymectomy was performed. A
      multilocular, non-invasive tumor mass was completely resected. Pathological
      diagnosis was lymphoid follicular hyperplasia with concomitant multilocular
      thymic cyst( MTC). Surgery resulted in alleviation of RA symptoms and a decreased
      inflammatory response. Inflammation due to autoimmune disease is believed to play
      an important role in the formation of MTC. In the present case, surgery may have
      inhibited the progression of RA.

PMID- 22374596
TI  - [Chest wall reconstruction with rectus abdominis musculocutaneous flap for
      sternum osteomyelitis after radiation].
AB  - We report a case of reconstruction of radiation ulcer on the chest wall and
      sternum osteomyelitis using a rectus abdominis musculocutaneous flap. A case of
      67-year-old woman, Halsted operation was performed for right breast cancer, 23
      years ago. After 4 years, transcatheter arterial injection and radiation therapy
      was performed to treat recurrence of parasternal lymph nodes. Since then, she had
      been without recurrence of the tumor, but suffered from repeated scabbing of
      parasternal skin. In 2009, she suffered from pain, redness and purulent discharge
      of the wound, and diagnosed with sternum osteomyelitis. She was admitted to our
      hospital and underwent debridement of sternum, and the resection of surrounding
      skin. Sixteen days later, reconstruction using a rectus abdominis
      musculocutaneous flap was performed. Twenty months after the operation, she is
      well without any evidence of recurrence.

PMID- 22374597
TI  - [Successful surgical case of DeBakey III b dissecting aortic aneurysm associated
      with right-sided aortic arch].
AB  - A 66-year-old man was admitted to our institute for surgical treatment of chronic
      dissecting aortic arch aneurysm with right-sided aortic arch which occurred 2
      months previously. The size of the aortic arch aneurysm was larger than 6 cm.
      Total arch replacement using open stent grafting was performed through median
      sternotomy. The postoperative condition was well, and the patient was discharged
      without any complications.

PMID- 22374598
TI  - [Prosthetic valve endocarditis associated with paravalvular aortic and mitral
      abscesses].
AB  - A 63-year-old female, who had undergone aortic and mitral valve replacement 16
      years ago, was admitted because of urinary tract infection. The patient developed
      cerebral hemorrhage. Methicillinresistant Staphylococcus aureus was isolated from
      her blood culture. Transesophageal echocardiography revealed paravalvular aortic
      and mitral abscesses, and the diagnosis of prosthetic valve endocarditis was
      established. A redo double valve replacement was performed. Both paravalvular
      abscess cavities were debrided and closed with fresh autologous pericardial
      patches, and mechanical valves were implanted. The patient's postoperative course
      was uneventful, and she had no sign of recurrent infection 3 years
      postoperatively.

PMID- 22374599
TI  - [Pacemaker infection developed one month after the surgery for prosthetic valve
      endocarditis].
AB  - A 57-year-old man underwent mitral valve replacement and tricuspid annuloplasty
      for mitral and tricuspid regurgitation. Pacemaker implantation was conducted
      because of postoperative sick sinus syndrome 2 months after the operation. One
      year later, the patient was readmitted to the hospital because of high fever.
      Echocardiography showed 2 vegetations of 10 mm in diameter attached to the mitral
      mechanical valve. No vegetations were detected on the tricuspid valve or the
      pacemaker leads. Mitral valve re-replacement was urgently performed under the
      diagnosis of prosthetic valve endocarditis caused by Staphylococcus aureus. One
      month after the reoperation, pacemaker infection developed in spite of suitable
      infection control by daily intravenous injection of sensitive antibiotics. We
      proceeded to place a temporary pacing wire and extracted the entire permanent
      pacing system. A new permanent pacemaker was implanted 5 days later. The patient
      was discharged on the 62th postoperative day without recurrence of infection.

PMID- 22374600
TI  - [Surgical treatment for deep pulmonary laceration with hemorrhagic shock].
AB  - 59-year-old man falling from the roof was transported to our hospital by
      ambulance. When thoracic drainage was done for tension pneumothorax of the left
      lung, massive intrathoracic hemorrhage was noted as well. Chest computed
      tomography (CT) revealed contusion of left lower lobe. Emergency operation was
      done, but complete hemostasis was not achieved. To control hemorrhage from lung,
      intrathoracic packing was performed. After improving general condition, left
      pneumonectomy could be performed by 2nd operation. His postoperative course was
      uneventful.

PMID- 22374601
TI  - [Postoperative refractory chylothorax which was improved by octreotide acetate].
AB  - A 77-year-old male with chronic hepatitis and liver cirrhosis underwent a right
      middle-lower lobectomy and lymph node dissection because of non-small cell
      carcinoma of the lung. On the 1st post-operative day (POD1), a large quantity of
      chylous pleural effusion was recognized after he initiated oral intake. The
      diagnosis was postoperative chylothorax. Conservative therapy including a medium
      chain tryglyceride diet and total parental nutrition were not effective.
      Considering of the patient's past history, we decided to continue conservative
      therapy using octreotide acetate on POD7. After administration of the octreotide
      acetate, the volume of chylous pleural effusion gradually decreased. The chest
      tube was removed on POD19. Octeotide acetate should be a choice for the
      conservative treatment of postoperative refractory chylothorax.

PMID- 22374602
TI  - [Cause and prevention of surgical site infection and hypertrophic scars].
AB  - Surgical site infection (SSI) occurs at the site of surgery within 1 month of an
      operation or within 1 year of an operation if a foreign body is implanted as part
      of the surgery. Most SSIs (about 70%) are superficial infections involving the
      skin and subcutaneous tissues only. The remaining infections are more serious and
      can involve tissues under the skin, organs, or implanted material. Hypertrophic
      scars( HSs) occur frequently on particular sites, including the anterior chest
      wall. The anterior chest wall is frequently subjected to skin stretching caused
      by the natural daily movements of the body. Most cases of SSIs and HSs can be
      prevented by (1) suture technique modification to prevent high stretching tension
      and ischemia, and (2) appropriate wound care after surgery. It would be useful to
      avoid subjecting wounded skin to sustained mechanical force, thereby permitting
      the wound to rest and heal normally.

PMID- 22374603
TI  - [Reoperative off-pump coronary revascularization via left thoracotomy using the
      PAS-Port system to the descending thoracic aorta: report of a case].
AB  - We performed redo-off-pump coronary artery bypass grafting( OPCAB) via a left
      thoracotomy using the PAS-Port system for proximal vein graft anastomoses in a
      patient with posterolateral myocardial ischemia. The patient was a 76-year-old
      man who had undergone coronary artery bypass grafting (CABG)[ left internal
      thoracic artery( LITA)-left anterior descending artery( LAD), saphenous vein
      graft(SVG)-posterior descending artery( 4PD), and SVG-postero-lateral branch(
      PL)] 14 years previously. Coronary angiogram showed that the LITA-LAD graft was
      patent but that the SVG-PL, left main trunk( LMT) and proximal right coronary
      artery(RCA) were occluded, and that there were 90% stenoses of LAD #7 and SVG-4PD
      anastomotic site. With catheter intervention therapy, stenosis of the SVG-#4PD
      was dilated. We then performed revascularization from the descending aorta to the
      second diagonal (D2) and PL with a saphenous vein graft via left thoracotomy
      using off-pump technique. To avoid descending aortic clamping, we used the PAS
      Port system for proximal anastomosis. The postoperative course was uneventful and
      the patient was discharged on postoperative day 28. A redo-CABG is thought to be
      with high risk. Our procedure, however is safe and useful and can be an option
      for redo-CABG in the posterolateral area.

PMID- 22374604
TI  - [Papillary fibroelastoma on the pulmonary valve ; report of a case].
AB  - We present a rare case of papillary fibroelastoma arising from the pulmonary
      valve. A 45-year-old man had been suffered from palpitation. Transthoracic
      echocardiography clearly demonstrated a mobile rounded mass in the right
      ventricular outflow tract. He underwent surgical extirpation of the tumor. A
      fragile, yellow tumor on the pulmonary valve was recognized at operation. The
      pulmonary valve was repaired with autologous pericardium. Operation was performed
      successfully. The diagnosis as a papillary fibroelastoma was made by
      histopathological examination. The post-operative course was uneventful and
      echocardiography showed no residual tumor of the heart.

PMID- 22374605
TI  - [Recurrent mediastinal desmoid tumor treated by surgical resection ; report of a
      case].
AB  - We report a rare case of mediastinal desmoid tumor in a 17-year-old man. The
      patient was a 17-year old man who had underwent surgery for mediastinal tumor at
      our hospital 2 years before. The tumor was diagnosed as a solitary fibrous tumor
      of the mediastinum. After 2 years, chest computed tomography(CT) and magnetic
      resonance imaging( MRI) showed a mass at the previously resected site. Surgery
      was performed again under the diagnosis of recurrent tumor. The tumor densely
      adhered to the superior vena cava, right innominate vein, pericardium, and the
      right lung. The tumor was completely resected with the aid of the partial
      extracorporeal circulation. Finally, both previously resected tumor and the
      recurrent tumor were diagnosed pathologically as desmoid tumors.

PMID- 22374606
TI  - [Lung cancer incidentally detected at the treatment of pneumothorax ; report of
      two cases].
AB  - We report 2 cases of lung cancer incidentally detected following pneumothorax.
      Case 1:A 40-year-old man complaining of dyspnea was admitted with right
      pneumothorax. Chest computed tomography (CT) after chest drainage showed a
      cavitary nodule with pleural indentations in the right lower lobe. It was
      indicated at surgery that pneumothorax was caused by perforation of the tumor
      into the pleural cavity. Right lower lobectomy was performed because the
      pathological diagnosis of the nodule was a large cell carcinoma. The final
      histopathological diagnosis was stage II A (pT2aN1M0). The patient died of
      recurrence 14 months after surgery. Case 2:A 47-year-old man who admitted with
      right pneumothorax was found to have a nodule with pleural indentations closely a
      bulla at the apex of the right lung by chest CT after chest drainage.
      Pneumothorax was indicated to be caused by rupture of the bulla at surgery. Right
      upper lobectomy was performed because the pathological diagnosis of the nodule
      was a squamous carcinoma. The final histopathological diagnosis was stage I A
      (pT1bN0M0). The patient is alive at 2 years after the operation without
      recurrence. Lung cancer detected following pneumothorax which was caused by
      perforation of the tumor is generally considered to have poor prognosis. Whereas,
      prognosis of lung cancer incidentally detected following pneumothorax depends on
      its staging.

PMID- 22374607
TI  - Proteomic analysis of primary colon cancer-associated fibroblasts using the SELDI
      ProteinChip platform.
AB  - OBJECTIVE: Cancer-associated fibroblasts (CAFs) are one of the hallmarks of the
      cancer microenvironment. Recent evidence has indicated that CAFs are more
      competent in enhancing cancer cell growth and migration than normal fibroblasts.
      However, the unique protein expression of CAFs has not been fully elucidated.
      This study aims to investigate the characterizations of colon CAFs by comparing
      the differential protein expression between CAFs and normal fibroblasts. METHODS:
      Primary fibroblasts were isolated from surgical specimen of human colon cancer
      and matched normal colonic tissue. Purity of the cell population was verified
      through immunostain analysis. Total cell lysates and conditioned media from each
      group of cells were extracted, and protein expression analysis was conducted
      using the surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) ProteinChip platform. RESULTS: Most primary cells
      showed typical fibroblast-like features after two weeks. Increased proportion of
      alpha-smooth muscle actin-positive myofibroblasts was detected within the CAFs in
      four of the six pairs of primary cells. Fibroblast activation protein was weakly
      expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip
      platform, four protein peaks mass over charge ratio (m/z) 1142, 3011, 4035, and
      4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and
      1389 were detected in the conditioned media. The potential candidate proteins
      found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide
      related peptides, insulin-like growth factor II, thymosin beta-4-like protein 3,
      and tight junction-associated protein 1. CONCLUSIONS: Using the SELDI-ProteinChip
      platform, differential protein expressions were identified in colon CAFs compared
      with normal colonic stromal fibroblasts. The complex proteomic alternations in
      colon CAFs may play important roles related to the colon cancer microenvironment.

PMID- 22374608
TI  - Expression level of pre-B-cell leukemia transcription factor 2 (PBX2) as a
      prognostic marker for gingival squamous cell carcinoma.
AB  - OBJECTIVE: In this study, we investigated the interrelationship between
      clinicopathologic findings and pre-B-cell leukemia transcription factor 2 (PBX2)
      expression in gingival squamous cell carcinoma (GSCC). METHODS: Expression level
      of PBX2 was immunohistochemically examined in 66 GSCC subjects (30 men and 36
      women) with ages ranging from 42 to 85 (median 64.5) years, in which staining
      intensity in tumor cells was categorized as either weaker (level 1) or equal
      to/stronger (level 2) than that in the endothelial cells. RESULTS: PBX2
      expression is correlated with valosin-containing protein (VCP) expression.
      Univariate and multivariate analyses revealed a high level of PBX2 expression to
      be a poor prognosticator for disease-free survival (DFS) and overall survival
      (OS), and PBX2 expression was an independent prognostic factor for both DFS and
      OS in GSCC. CONCLUSIONS: PBX2 expression level in GSCC is prognostic. PBX2 may be
      a useful marker to identify the potential for progression in GSCC.

PMID- 22374609
TI  - Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract against
      paracetamol-induced nephrotoxicity and oxidative stress in rats.
AB  - Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one
      of the possible mechanisms mediating the event. In this study, the effects of
      ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight
      (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were
      divided into five groups containing 10 rats each. The control group received
      distilled water while other groups were treated with extract alone (400 mg/kg),
      PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+200-extract), and 750
      mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven
      consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent
      with oral administration of PCM. Treatment with Z. zerumbet extract at doses of
      200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative
      impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level
      of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein
      carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both
      doses were also able to induce a significant increment (P<0.05) of plasma and
      renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity.
      The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced
      intensity of renal cellular damage, as evidenced by histological findings.
      Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater
      protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract
      of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity
      and the process is probably mediated through its antioxidant properties.

PMID- 22374610
TI  - Saline conducted electric coagulation (SCEC): original experience in experimental
      hepatectomy.
AB  - OBJECTIVE: To evaluate the feasibility and superiority of a new coagulating and
      hemostatic method named "saline conducted electric coagulation (SCEC)". METHODS:
      The Peng's multifunction operative dissector (PMOD) was modified to enable saline
      to effuse persistently out of its nib at a constant speed. In a group of six New
      Zealand rabbits, two hepatic lobes of each rabbits were resected respectively by
      SCEC and conventional electric coagulation (EC). The features of SCEC were
      recorded by photo and compared with conventional EC. After 7 d, the coagulating
      depth was measured in each residual hepatic lobe. Hepatic tissue was dyed by
      hematoxylin and eosin (HE) and studied under a microscope. RESULTS: The
      coagulating depth increased with the continuation of SCEC time. Hepatectomies
      were performed successfully, no rabbit died in the perioperative period. The
      incisal surface of SCEC was gray-white with no red bleeding point. There was a
      thick solidified layer at the margin and a thin red-white intermittent layer
      between the solidified layer and normal hepatic tissue at the vertical section of
      SCEC. The mean coagulating depth of SCEC was 1.8 cm vs. 0.3 cm of conventional
      EC. Pathological examination showed a mild inflammatory reaction by SCEC.
      CONCLUSIONS: SCEC is a feasible and safe method for surgical hemostasis. As a new
      technique for liver resection, SCEC shows better coagulating effect and milder
      inflammatory reaction than conventional EC. Our study shows bloodless liver
      resection can also be performed by SCEC, especially for liver malignant tumor.

PMID- 22374611
TI  - A meta-analysis of association between acne vulgaris and Demodex infestation.
AB  - Until now, etiology of acne vulgaris is still uncertain. Although clinicians
      usually deny the association between Demodex infestation and acne vulgaris, it
      has been proved in some clinical practices. To confirm the association between
      Demodex infestation and acne vulgaris, a meta-analysis was conducted. Predefined
      selection criteria were applied to search all published papers that analyzed the
      association between Demodex infestation and acne vulgaris (January 1950 to August
      2011) in ISI Web of Knowledge, MEDLINE, and China National Knowledge
      Infrastructure (CNKI) databases. A meta-analysis was performed to calculate odds
      ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or
      random effects models. We enrolled the 60 Chinese and 3 English papers in this
      meta-analysis, which covered Turkey and 25 different provinces/municipalities in
      China and 42130 participants including students and residents, aged from 1 to 78
      years. The pooled OR in random effects models is 2.80 (95% CI, 2.34-3.36).
      Stability is robust according to sensitivity analysis. The fail-safe number is
      18477, suggesting that at least 18477 articles with negative conclusions would be
      needed to reverse the conclusion that acne vulgaris was related to Demodex
      infestation. So the effect of publication bias was insignificant and could be
      ignored. It was concluded that acne vulgaris is associated with Demodex
      infestation. This indicates that when regular treatments for acne vulgaris are
      ineffective, examination of Demodex mites and necessary acaricidal therapies
      should be considered.

PMID- 22374612
TI  - Evaluation of intratympanic dexamethasone for treatment of refractory sudden
      sensorineural hearing loss.
AB  - OBJECTIVE: To observe and compare the efficacy of intratympanic application of
      dexamethasone (DXM) for the treatment of refractory sudden sensorineural hearing
      loss (SSNHL), the DXM was given in three different ways: by tympanic membrane
      injection, by drip through a ventilation tube, and by perfusion through a round
      window catheter. METHODS: We conducted a nonrandomized retrospective clinical
      trial involving 55 patients with refractory SSNHL. For 21 patients (the perfusion
      group), DXM (2.5 mg/0.5 ml) was perfused transtympanically through a round window
      catheter using an infusion pump for 1 h twice a day for 7 d giving a total amount
      of 35.0 mg. For 23 patients (the injection group), DXM (2.5 mg/time) was injected
      by tympanic membrane puncture at intervals of 2 d on a total of four occasions
      giving a total amount of 10.0 mg. For 11 patients (the drip group), DXM (2.5
      mg/0.5 ml) was dripped via a ventilation tube placed by myringotomy, once on the
      first day and twice a day for the remaining 6 d giving a total amount of 32.5 mg.
      Thirty-two patients with refractory SSNHL who refused to undertake further
      treatments were defined as the control group. Hearing recovery and complications
      were compared among the groups. Hearing results were evaluated based on a four
      frequency (0.5, 1.0, 2.0, 4.0 kHz) pure tone average (PTA). RESULTS: Post
      treatment audiograms were obtained one month after treatments were completed. The
      improvements in average PTA for the perfusion, injection, and drip groups were
      9.0, 8.6, and 1.7 dB, respectively. Hearing improvement was significantly greater
      in the perfusion and injection groups than in the control group (1.4 dB)
      (P<0.05). In the perfusion group, 8 out of 21 patients (38.1%) had a PTA
      improvement of 15-56 dB (mean 29.8 dB); in the injection group, 8 out of 23
      patients (34.8%) had a PTA improvement of 16-54 dB (mean 24.9 dB); in the drip
      group, 1 of 11 patients (9.1%) had a PTA improvement of 26.0 dB; in the control
      group, 3 out of 32 patients (9.4%) had a PTA improvement of 15-36 dB (mean 14.9
      dB). CONCLUSIONS: Topical intratympanic application of DXM is a safe and
      effective method for the treatment of SSNHL cases that are refractory to
      conventional therapies.

PMID- 22374613
TI  - Use of digital subtraction angiography for assessment of digital replantation.
AB  - OBJECTIVE: To assess the blood flow of the proper digital artery using digital
      subtraction angiography (DSA) in the early stage after replantation. METHODS:
      From January 2006 to October 2010, 27 anastomosed arteries in 27 replanted digits
      were included in the study. The patients included nine males and four females.
      The patients received DSA at 48 to 96 h after digital replantation. Based on DSA
      image, the blood flow was classified into normal, slow-running, and flow-stopping
      types. The patients with normal digital blood flow were given continuous routine
      treatments; the patients with slow-running flow were given the conservative
      treatments, such as release of the tight dressings, removal of stitches, keeping
      warm, the use of massage, and the use of anticoagulants and anti-inflammatory
      drugs; the patients with flow-stopping received immediate surgical re
      exploration. RESULTS: In this series, 23 digits in 11 patients showed a normal
      blood flow, and these digits all survived. In one of 13 patients, two digits
      which displayed slow-running flow also survived after conservative treatments. In
      two of 13 patients, two digits showed flow stopping, with one surviving and one
      failing after re-exploration and arterial revision. CONCLUSIONS: The DSA can be
      used to assess the blood flow of the proper digital artery in the early stage
      after replantation. It provides essential information for salvaging the replanted
      finger.

PMID- 22374614
TI  - Permeation of dimethyl sulfoxide into articular cartilage at subzero
      temperatures.
AB  - Osteochondral allografting has been proved to be a useful method to treat
      diseased or damaged areas of joint surfaces. Operational long-term stocks of
      grafts which supply a buffer between procurement and utilization would contribute
      to the commercialization or industrialization of this technology. Vitrification
      has been thought to be a promising method for successful preservation of
      articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used
      which may cause high cellular toxicity. An effective way to reduce CPA toxicity
      is to increase CPA concentration gradually while the temperature is lowered.
      Understanding the mechanism of CPA permeation at subzero temperatures is
      important for designing the cryopreservation protocol. In this research, the
      permeation of dimethyl sulfoxide (Me(2)SO) in ovine AC at subzero temperatures
      was studied experimentally. Pretreated AC discs were exposed in Me(2)SO solutions
      for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature
      levels (-10, -20, and -30  degrees C). The Me(2)SO concentration within the
      tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion
      coefficients were estimated to be 0.85*10(-6), 0.48*10(-6), and 0.27*10(-6)
      cm(2)/s at -10, -20, and -30  degrees C, respectively, and the corresponding
      activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare
      two Me(2)SO addition protocols, and the results demonstrated that the total
      loading duration could be effectively reduced with the knowledge of permeation
      kinetics.

PMID- 22374615
TI  - Effects of the duration of expressions on the recognition of microexpressions.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of the
      duration of expressions on the recognition of microexpressions, which are closely
      related to deception. METHODS: In two experiments, participants were briefly
      (from 20 to 300 ms) shown one of six basic expressions and then were asked to
      identify the expression. RESULTS: The results showed that the participants'
      performance in recognition of microexpressions increased with the duration of the
      expressions, reaching a turning point at 200 ms before levelling off. The results
      also indicated that practice could improve the participants' performance.
      CONCLUSIONS: The results of this study suggest that the proper upper limit of the
      duration of microexpressions might be around 1/5 of a second and confirmed that
      the ability to recognize microexpressions can be enhanced with practice.

PMID- 22374617
TI  - Structural and functional changes in gill mitochondrial membranes from the
      Mediterranean mussel Mytilus galloprovincialis exposed to tri-n-butyltin.
AB  - The use of tributyltin (TBT) as a biocide in antifouling paints leads to a
      ruinous input of this contaminant in the aquatic environment. Human exposure to
      TBT mainly occurs through ingestion of contaminated seafood such as filter
      feeding mollusks. Tributyltin is known to act as a membrane-active toxicant on
      several targets, but especially on the mitochondria, and by several mechanisms.
      The effects of tributyltin on fatty acid composition, on Mg-adenosine
      triphosphatase (ATPase) activities, and on the membrane physical state were
      investigated in gill mitochondrial membranes from cultivated mussels Mytilus
      galloprovincialis exposed to 0.5 ug/L and 1.0 ug/L TBT and unexposed for 120 h.
      The higher TBT exposure dose induced a decrease in the total and n-3
      polyunsaturated fatty acids (PUFAs), especially 22:6 n-3, and an activation of
      the oligomycin-sensitive Mg-ATPase. Both TBT concentrations decreased
      mitochondrial membrane polarity detected by Laurdan steady-state fluorescence
      spectroscopy. These findings may help cast light on the multiple modes of action
      of this toxicant.

PMID- 22374616
TI  - Influence of education and working background on physicians' knowledge of
      secondary prevention guidelines for coronary heart disease: results from a survey
      in China.
AB  - BACKGROUND AND OBJECTIVE: In clinical practice, the standard of secondary
      prevention for coronary heart disease (CHD) is quite disappointing in China. The
      physicians' shortage of knowledge of secondary prevention guidelines is thought
      to be a key factor contributing to the inadequate and delayed translation of
      guidelines into clinical practice. The purpose of this study is to investigate
      the influence of physicians' characteristics, including their education and work
      experience, on their knowledge of secondary prevention in China. METHODS: A
      representative questionnaire survey was made of physicians from cardiology
      departments in 35 tertiary hospitals in China. The survey contained 19 questions
      on knowledge of guideline recommendations for the secondary prevention of CHD. We
      collected basic information about the physicians, including their educational
      degree, clinical practice duration/work experience and geographic region.
      RESULTS: In total, 864 physicians participated in the survey. Eight hundred and
      thirty-seven completed questionnaires were analyzed. For 6 of the 19 questions,
      physicians with a postgraduate degree were more likely to answer correctly than
      those without such a degree. For 11 of the 19 questions, physicians with more
      than three years' clinical experience were more likely to answer correctly than
      those who had less than three years' experience. For 5 of the 19 questions,
      physicians from eastern areas were more likely to answer correctly than those
      from mid/western areas. The mean total score of correct answers to the
      questionnaire was 11.69 points. Educational degree and clinical practice duration
      affected total scores significantly while practice location did not (beta=0.500,
      P=0.004; beta=0.979, P=0.000; and beta=0.228, P=0.162, respectively). Even if a
      relatively low score of 12 is taken as a threshold level of acceptable knowledge
      (defined as a pass), the pass rate of all physicians was only 53.9%. Educational
      degree and clinical practice duration affected pass rate significantly while
      practice location did not (95% CI: 1.222-2.248, P=0.001; 95% CI: 1.773-3.140,
      P=0.000; and 95% CI: 0.993-1.758, P=0.056, respectively). CONCLUSIONS: Physicians
      with a clinical practice duration of more than three years knew more about
      secondary prevention guidelines than those with less experience. Physicians with
      a postgraduate degree knew more about secondary prevention guidelines than those
      without a postgraduate degree. However, overall knowledge of secondary prevention
      guidelines for CHD was poor among this group of physicians from tertiary
      hospitals.

PMID- 22374618
TI  - How does measured olfactory function correlate with self-ratings of the sense of
      smell in patients with nasal polyposis?
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study were to investigate
      correlations, before and after surgery, between olfactory function self-ratings
      and measurements, and self-ratings of nasal obstruction and smell; and to
      establish cutoff points of self-rating scores for smell reduction in patients
      with nasal polyposis (NP). STUDY DESIGN: Prospective study. METHODS: A total of
      80 patients with NP (36 women, 44 men; aged 49 +/- 4 years) were enrolled. Self
      ratings (0- to 10-point scale) and measurements of olfactory function with
      standardized Sniffin' Sticks odor threshold and identification tests were
      assessed 1 day before surgery, and at 6 weeks (26-78 days) and 7 months (132-318
      days) after surgery. Relationships were studied with Spearman correlation
      coefficients. Cutoff points of self-rating scores for olfactory deficit were
      established using the receiver operating characteristic curve. RESULTS: Overall,
      olfactory function self-ratings and measurements correlated strongly
      preoperatively (r = -0.66, P < .0001) and postoperatively (r = -0.67 at 6 weeks
      and -0.66 at 7 months, P < .0001). This relationship was better in patients with
      previous surgery. The correlation was weaker before surgery (r = -0.35, P = .01)
      than after in hyposmic/anosmic patients (r = -0.74, P < .0001 at 6 weeks and r = 
      0.73, P = .0002 at 7 months) and was not found in normosmic patients. Self
      ratings of nasal patency and smell were not correlated when two complaints were
      dissociated. Cutoff points of self-rating scores for smell reduction were nine
      units preoperatively and five units postoperatively. CONCLUSIONS: Self-ratings
      and measurements of olfactory function correlated well before and after surgery
      in NP patients with olfactory deficits. Self-ratings were not reliable pre- and
      postoperatively in normosmic patients.

PMID- 22374619
TI  - Paclitaxel and iron oxide loaded multifunctional nanoparticles for chemotherapy,
      fluorescence properties, and magnetic resonance imaging.
AB  - The multifunctional nanoparticles constructed from triphenylamine-poly(lactide-co
      glycolide)-poly(ethyleneglycol)-poly(lactide-co-glycolide) (TPA-PEP) and folate
      poly(2-ethyl-2oxazoline)-poly(D,L-lactide) (folate-PEOz-PLA) were developed in
      this study. Iron oxide nanoparticles (IOP) and paclitaxel (PTX) were
      coencapsulated in the nanoparticles with diameter less than 200 nm. The drug
      loaded nanoparticles emit fluorescence peak at 460 nm when excited with
      wavelength of 350 nm. The in vitro antitumor activity of the drug-loaded
      nanoparticles was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays against HeLa cells. When the cells were
      exposed to the nanoparticles with different levels of folate but the same drug
      loading, cell viability decreases as the level of folate increases. Confocal
      laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for
      the non-folate-nanoparticles than that for the folate-nanoparticles. The in vitro
      and in vivo magnetic resonance imaging (MRI) studies indicate the better T2
      Weighted images can be obtained for the folate-nanoparticles. In the anticancer
      effect evaluation, tumor-bearing mice administered with the 30%-folate
      nanoparticles showed ~50% reduction in tumor volume after 23 days. The
      multifunctional nanoparticles as drug carrier with capabilities of both tumor
      targeting and MRI present a new direction in drug delivery system development.

PMID- 22374620
TI  - Carbon-supported molybdenum carbide catalysts for the conversion of vegetable
      oils.
AB  - Ordered mesoporous carbon (OMC)-supported molybdenum carbide catalysts were
      successfully prepared in one pot using a solvent-evaporation-induced self
      assembly strategy accompanied by a carbothermal hydrogen reduction reaction.
      Characterization with nitrogen sorption, small-angle XRD, and TEM confirmed that
      the obtained materials had high surface areas, large pore volumes, ordered
      mesoporous structures, narrow pore size distributions, and uniform dispersions of
      molybdenum carbide particles. With nitrogen replaced by hydrogen in the
      carbothermal reduction reaction, the formation temperature of molybdenum carbide
      could be reduced by more than 100  degrees C. By changing the amount of
      molybdenum precursor added from less than 2 % to more than 5 %, molybdenum
      carbide structures could be easily regulated from Mo(2) C to MoC. The catalytic
      performance of OMC-supported molybdenum carbide catalysts was evaluated by
      hydrodeoxygenation of vegetable oils. Compared with Mo(2)C, MoC exhibited high
      product selectivity and excellent resistance to leaching in the conversion of
      vegetable oils into diesel-like hydrocarbons.

PMID- 22374621
TI  - Construction of a graphene oxide based noncovalent multiple nanosupramolecular
      assembly as a scaffold for drug delivery.
AB  - A multiple supramolecular assembly, in which a folic acid-modified beta
      cyclodextrin (1) acted as a target unit, an adamantanyl porphyrin (2) acted as a
      linker unit, and graphene oxide acted as a carrier unit, was successfully
      fabricated through non-covalent interactions and comprehensively investigated by
      means of UV/Vis, fluorescence, and X-ray photoelectron spectroscopies, and
      electron microscopy. Significantly, the graphene oxide unit could associate with
      the anticancer drug doxorubicin through pi-pi interactions, and the folic acid
      modified beta-cyclodextrin unit could recognize the folic acid receptors in
      cancer cells. Owing to the cooperative contribution of these three units, the
      resulting multiple supramolecular assembly, after association with doxorubicin,
      exhibited better drug activity and much lower toxicity than free doxorubicin in
      vivo.

PMID- 22374622
TI  - Cyclic SiS2: a new perspective on the Walsh rules.

PMID- 22374623
TI  - The contribution of different prion protein types and host polymorphisms to
      clinicopathological variations in Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease is a fatal neurodegenerative disease that primarily
      affects the central nervous system. In this respect, it can be considered
      alongside the more frequently occurring neurodegenerative diseases, such as
      Alzheimer's disease. Creutzfeldt-Jakob disease is perhaps the paradigmatic
      protein misfolding disorder, so comparisons between the mechanisms involved in
      Creutzfeldt-Jakob disease and other neurodegenerative diseases associated with
      protein misfolding (such as the tauopathies and synucleinopathies) may also be
      informative. Like many of these diseases, Creutzfeldt-Jakob disease occurs
      sporadically or can, more rarely, be associated with mutations. However,
      Creutzfeldt-Jakob disease can also be acquired and is experimentally
      transmissible. These properties have had profound public health implications and
      made the disease of interest to virologists, in addition to those interested in
      protein misfolding disorders and neurodegeneration. The possible causes for the
      pronounced phenotypic variation among different forms of Creutzfeldt-Jakob
      disease are beginning to become understood, and these appear to depend in large
      measure on the genetics of the host (specifically the sequence of the prion
      protein gene, PRNP) and the epigenetic aspects of the agent (thought to be a
      misfolded and aggregated form of the PRNP gene product, termed a prion). This
      review will examine whether this model in its present form has sufficient
      complexity and subtlety to account for the clinicopathological variation evident
      in Creutzfeldt-Jakob disease and will outline the ways in which a more complete
      and informative molecular definition of human prions are currently being sought.

PMID- 22374624
TI  - Levothyroxine dose following thyroidectomy is affected by more than just body
      weight.
AB  - OBJECTIVES/HYPOTHESIS: To determine the factors that affect levothyroxine (LT4)
      requirements following thyroidectomy. STUDY DESIGN: Retrospective study. METHODS:
      This study evaluated 246 participants who had undergone total thyroidectomy and
      were on a stable dose of LT4. Actual weight-based (AWB) and ideal body weight
      based (IBWB) LT4 dose requirements were analyzed, and other confounders including
      adherence, concurrent medications, comorbidities, female menopausal status, and
      hormone replacement therapy were examined. RESULTS: A total of 205 women and 41
      men were evaluated, with 48 (20%) benign and 198 (80%) malignant pathology
      findings. The mean AWB LT4 doses for men and premenopausal women were similar
      among members of the benign groups and similar among members of the malignant
      groups. There was a trend for lower dose LT4 in postmenopausal women off hormonal
      therapy (PM/NH) and on hormonal therapy (PM/H) in the benign group (1.4 and 1.6
      MUg/kg vs. 1.8 MUg/kg in the men and premenopausal women) and a trend for lower
      dose LT4 in the PM/H women in the malignant group (1.9 MUg/kg vs. 2.1 and 2.2
      MUg/kg in the men and premenopausal women), but they were not significant.
      However, PM/NH women required significantly less LT4 (1.7 MUg/kg) than both the
      men (2.2 MUg/kg) and premenopausal women (2.1 MUg/kg) in the malignant group
      (P=.0006). The IBWB LT4 dosage was not statistically different between groups.
      CONCLUSIONS: LT4 dosage following thyroidectomy, calculated using actual body
      weight, can range from 1.4 to 2.2 MUg/kg and is dependent on diagnosis (benign
      vs. malignant), goal TSH, sex, and menopausal status.

PMID- 22374625
TI  - [Clinical correlates of social anxiety disorder comorbidity in schizophrenia].
AB  - OBJECTIVE: The aim of this study is to investigate the social anxiety disorder
      comorbidity and clinical features in schizophrenia. METHOD: 102 (23 women and 79
      men) outpatients who had been followed in the Psychotic Disorders Unit in
      Bakirkoy Research and Training Hospital for Psychiatry, Neurology and
      Neurosurgery were diagnosed with schizophrenia according to DSM-IV criteria were
      included in the study. Schizophrenia and Social anxiety disorder  were assessed
      by a structured clinical interview for DSM-IV. Patients were evaluated with a
      questionnaire which included demographics, clinical characteristics, Liebowitz
      social anxiety scale, Positive and Negative Syndrome Scale (PANSS), Calgary
      depression scale for schizophrenia (CDSS),The Scale of Unawareness of Mental
      Disorders (SUMD), Short form-36 health survey questionnaire and state-trait
      anxiety inventory. RESULTS: In remission, 22 patients (21.6%) had co-morbid
      social anxiety disorder. Patients with social anxiety disorder comorbidity, had
      higher levels of awareness. Their depression scores were higher and functional
      impairments were lower. These patients had been treated with typical and atypical
      antipsychotics and antidepressants. CONCLUSION: Social anxiety disorder
      comorbidity in schizophrenia adversely affects  the quality of life and is not
      rare. Future studies should be planned with the assesment of social anxiety
      disorder treatment as well as schizophrenia treatment.

PMID- 22374626
TI  - [Comparison of the effectiveness of cognitive restructuring and systematic
      desensitization in reducing high-stakes test anxiety].
AB  - OBJECTIVE: This study aimed to compare the effectiveness of systematic
      desensitization (behavioral therapy and cognitive restructuring (cognitive
      therapy) in reducing high-stakes test anxiety. We hypothesized that cognitive
      restructuring would be superior to systematic desensitization in reducing the
      severity of the cognitive symptoms of anxiety, whereas systematic desensitization
      would be superior to cognitive restructuring in reducing the severity of the
      physiological symptoms of anxiety. MATERIALS AND METHOD: The study included 50
      (36 female and 14 male) high school graduates and high school seniors aged 16-22
      years (mean:18.3 years) that experienced test anxiety while taking their
      university entrance exam. Participants were randomly assigned to the behavior
      therapy or cognitive therapy groups. Participants in both groups received 9
      sessions of structured group therapy with the same therapist. Each participant's
      level of anxiety and depression, psychiatric symptoms, and dysfunctional thoughts
      were measured throughout the therapy process. RESULTS: Statistical analysis
      showed that there was a significant decrease in the score of each outcome measure
      employed in both groups. There weren't any significant differences in terms of
      the alleviation of the cognitive symptoms of anxiety, as measured with the
      Dysfunctional Attitudes Scale, or physiological symptoms, as assessed with the
      Beck Anxiety Inventory between the 2 groups. The 2 therapy methods resulted in
      statistically significant reductions in the level of test anxiety, as well as
      state anxiety, trait anxiety, self-reported depression, and general symptom
      levels. CONCLUSION: The behavioral and cognitive therapies were equally effective
      in reducing the severity of the cognitive and physiological components of test
      anxiety.

PMID- 22374627
TI  - [The role of interpersonal style, self perception and anger in sexual
      dysfunction].
AB  - PURPOSE: The main purpose of this study was to determine the relationship between
      interpersonal style, self concept, and anger in the context of sexual
      dysfunction. METHOD: The sample consisted of males and females diagnosed as
      having sexual dysfunction (N=95) and males and females without a diagnosis of any
      kind of psychological disorder (N=95). The age range was between 18-53. The
      participants were given a detailed Demographic Information Questionnaire and the
      Interpersonal Styles Scale, Brief Symptom Inventory, Multidimensional Anger
      Scale, Social Comparison Scale and the  Golombok-Rust Inventory of Sexual
      Satisfaction (GRISS). RESULTS: The results showed that the two groups had
      significantly different scores on all of the measures, including their sub
      scales. The regression analyses of the two groups revealed that for all of the
      participants, males and females, patients and non-patients, the GRISS scores
      could be significantly predicted by self-perception, satisfaction with life and
      relationships. These three variables were the common variables that predicted the
      GRISS scores regardless of sex. However, the specific predictive variable for the
      GRISS scores of the female patients, in addition to the three common variables,
      was vindictive anger reactions. For the non-patient females, these additional
      variables were belittling and insensitive interpersonal styles. On the other
      hand, for the male patients, the scores on the GRISS could be significantly
      predicted by the belittling interpersonal style and aggressive anger reactions,
      along with the three common variables listed above. For the non-patient males,
      the additional variable was avoidant interpersonal style. CONCLUSION: The above
      results indicate that sexual dysfunctions can be explained in part by the
      interpersonal style and anger management deficits of the patients. It is
      suggested that the addition of anger-management, and interpersonal communication
      skills training courses into the treatment protocol of sexual dysfunction
      disorders would be beneficial.

PMID- 22374628
TI  - [Profile of population targeted by violent behavior of psychotic patients].
AB  - OBJECTIVE: The aim of this study is to examine the population targeted by the
      violent behavior of psychotic patients and to provide data on the treatment and
      therapeutic support of psychiatric professionals based on our results. METHOD:
      Eighty-one psychotic patients lacking criminal responsibility and under
      observation or mandatory treatment due to violent crime were compared with a
      control group of 31 persons with criminal responsibility. The sociodemographic
      features of the two groups' victims and descriptive data about the crimes and the
      target populations were examined and analyzed with SPSS 11. RESULTS: Patient and
      control groups were compared according to their relationships to their victims.
      Of psychotic patients' victims, 36.9% percent were family members, while in the
      non-psychotic group the proportion was 10%, a statistically significant
      difference (p<0.01). We also found a statistically significant difference between
      the two groups in the mean ages of their victims and in the proportions who
      victimized married people, had previously met with their victims or who lived
      with their victims prior to the homicidal act. CONCLUSION: This study concludes
      that violent psychotic patients mostly choose their victims from among their
      family members. Psychotic patients were three times more likely to choose a
      relative compared to the control group. Recognizing the risk factors and the
      population most often targeted by homicidal behavior is essential for protecting
      patients and the community.

PMID- 22374629
TI  - [Event-related potentials in major depressive disorder: the relationship between
      P300 and treatment response].
AB  - OBJECTIVE: Although conflicting results have been obtained regarding P300
      amplitude and latency in major depressive patients, most studies have reported
      that major depressive patients have smaller P300 amplitudes and longer latencies
      than healthy people. This study aimed to investigate the relationship between
      P300 and treatment response in major depressive disorder patients. METHODS:
      Twenty-eight patients suffering from major depression who completed 12 weeks of
      follow-up appointments and 28 healthy people, whose age and gender were matched
      with patients, were included in the study. Event-related potentials (P300) were
      recorded for patients before and after treatment with sertraline (50-200 mg/day)
      for 12 weeks. Treatment response was defined as a 50% or greater decrease in a
      given patient's total Hamilton Depression Rating Scale score. Pre-treatment and
      post-treatment P300 amplitude and latency values were compared for responders
      (n=18), non-responders (n=10) and healthy subjects. RESULTS: No significant
      difference was found between the P300 amplitude values of responders, non
      responders and healthy subjects before or after treatment. Pre-treatment P300
      latencies of non-responders were significantly longer than latencies of
      responders and healthy subjects. After treatment for depression, P300 latency
      values of responders were normalized, but non-responders still maintained longer
      P300 latencies than responders and healthy subjects. CONCLUSION: These findings
      suggest that delayed P300 latency may be related to a non-response to sertraline
      treatment. No relation was found between P300 amplitude and treatment response.

PMID- 22374630
TI  - [Burden and psychological distress among Nigerian family caregivers of
      schizophrenic patients: the role of positive and negative symptoms].
AB  - OBJECTIVE: To determine the relationship between symptoms of schizophrenia and
      caregiver burden/distress among caregivers of people with schizophrenia in
      southwestern Nigeria. METHOD: One hundred and one family caregivers of 101
      patients with schizophrenia were recruited into the study. Caregivers were
      screened with the Zarit Burden Interview (ZBI) to measure caregiver burden and
      the 30 item General Health Questionnaire (GHQ-30) to measure psychological
      distress. Patients were interviewed using the Brief  Psychiatric Rating Scale
      (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS) to rate
      psychopathology. RESULTS: More than half of the caregivers were females (58.4%).
      About one third of caregivers (33.7%) were experiencing moderate/severe levels of
      burden even though the mean burden score of 32.6+/- 14.1 for the sample was in
      the mild/moderate range on the ZBI scale. Using regression analysis, it was found
      that higher caregiver burden scores  were associated with negative symptoms of
      asociality-anhedonia, whereas high GHQ-30 scores were associated with inattention
      and avolition. High caregiver burden scores were also associated the patient
      being unemployed and the caregiver having lower education, whereas high levels of
      emotional distress in the caregiver was related to the patient being female and
      the patient having a lower education level. CONCLUSIONS: These results underscore
      the need for continued intervention for family members of Schizophrenic patients.
      Part of the care plan for the caregiver should include education on the negative
      symptoms of the illness.

PMID- 22374631
TI  - [Standardization of Turkish form of metacognition questionnaire for children and
      adolescents: the relationships with anxiety and obsessive-compulsive symptoms].
AB  - OBJECTIVE: There were two aims of the present study. The first aim was to
      evaluate the psychometric properties of the Metacognition Questionnaire for
      Children and Adolescents (MCQ-C) among Turkish children and adolescents. The
      second aim was to analyze relationships between metacognitive processes, anxiety,
      and obsessive-compulsive symptoms among Turkish children and adolescents. METHOD:
      Four hundred and seventy primary and high school students (205 female, 265 male)
      from 71 different public schools in Istanbul participated in the study. Three
      questionnaires were used. In addition to MCQ-C, State-Trait Anxiety Scale for
      Children and Maudsley Obsessive-Compulsive Inventory were administrated in the
      study. RESULTS: The Turkish form of MCQ-C showed acceptable to good test-retest
      reliability and good internal consistency and convergent validity. Construct
      validity was evaluated by confirmatory factor analysis using AMOS. The fit
      indices of confirmatory factor analysis suggested an acceptable fit to a four
      factor model consistent with the original MCQ-C. Significant positive
      correlations between subscales of MCQ-C and measures of anxiety and obsessive
      compulsive symptoms provided further support for the convergent validity of the
      Turkish form of MCQ-C. Group comparisons showed that the effect of age was
      significant on the MCQ-C positive meta-worry subscale only; on the other hand,
      effect of gender was significant on MCQ-C negative meta-worry subscale and total
      score. CONCLUSION: The psychometric properties of Turkish form of MCQ-C showed
      that the instrument is a valuable addition to the assessment of metacognition for
      Turkish children and adolescents.

PMID- 22374632
TI  - [Psychotic disorders among immigrants from Turkey in Western Europe: An overview
      of incidences, prevalence estimates, and admission rates].
AB  - OBJECTIVE: To provide an overview of incidence and prevalence estimates,
      admission rates, and related features of psychotic disorders among immigrants
      from Turkey in Western Europe. METHOD: Articles published in all languages
      between 1990 and 2010 were included. In order to detect relevant studies, a
      string ([schizo* OR psych*] AND [Turk*] AND [migra* OR immigra*]) was used in
      MEDLINE and PsychINFO. Turkish indexes and abstracts books of national congresses
      were also screened to locate additional papers. RESULTS: We included 21 studies
      which yielded 25 rates on psychotic disorders among immigrants from Turkey.
      Fifteen papers reported rates for the immigrants from Turkey in The Netherlands,
      four for Germany, one for Denmark and one for Switzerland. The incidence
      estimates of non-affective and affective psychosis among immigrants from Turkey
      were between 38.5 and 44.9 per 100,000 while incidence estimates of schizophrenia
      were between 12.4 and 63.8 per 100,000. The prevalence estimates of schizophrenia
      and other psychotic disorders were between 1.1 and 6.2 per 1,000. Rates and
      relative risks of psychotic disorders in immigrants from Turkey tended to be
      higher than the natives and lower than other immigrant groups with similar
      sociocultural background. In addition to other risk factors, social contextual
      factors including discrimination and neighbourhood characteristics were the key
      environmental factors that modulate rates of psychotic disorders among immigrants
      from Turkey. Males were under a higher risk of incidence, prevalence estimates,
      and admission rates. CONCLUSION: Variations in rates and relative risks indicate
      a possible etiological role of social experiences in immigrants. Studies with a
      focus on comparing the rates and the social factors of psychotic disorders
      between immigrants from Turkey in Western Europe and their family members
      residing in Turkey may provide additional insight into the epidemiology of
      psychotic disorders.

PMID- 22374633
TI  - [The effect of circumcision on the mental health of children: a review].
AB  - Circumcision is one of the oldest and most frequently performed surgical
      procedures in the world. It is thought that the beginning of the male
      circumcision dates back to the earliest times of history. Approximately 13.3
      million boys and 2 million girls undergo circumcision each year. In western
      societies, circumcision is usually performed in infancy while in other parts of
      the world, it is performed at different developmental stages. Each year in
      Turkey, especially during the summer months, thousands of children undergo
      circumcision. The motivations for circumcision include medical-therapeutic,
      preventive-hygienic and cultural reasons. Numerous publications have suggested
      that circumcision has serious traumatic effects on children's mental health.
      Studies conducted in Turkey draw attention to the positive meanings attributed to
      the circumcision in the community and emphasize that  social effects limit the
      negative effects of circumcision. Although there are many publications in foreign
      literature about the mental effects of the circumcision on children's mental
      health, there are only a few studies in Turkey about the mental effects of the
      one of the most frequently performed surgical procedures in our country. The aim
      of this study is to review this issue. The articles related to circumcision were
      searched by keywords in Pubmed, Medline, EBSCHOHost, PsycINFO, Turkish Medline,
      Cukurova Index Database and in Google Scholar and those appropriate for this
      review were used by authors.

PMID- 22374634
TI  - [Preface].

PMID- 22374635
TI  - Etiology of overactive bladder: a diet and lifestyle model for diabetes and
      obesity in older women.
AB  - OBJECTIVE: To evaluate a coherent, evidence-based hypothesis that specific
      modifiable lifestyle factors implicated in the development of diabetes and
      associated obesity are related to the onset of OAB. METHODS: A hypothetical
      causative model for OAB involving modifiable lifestyle factors implicated in the
      development of diabetes and obesity was constructed, based on a systematic
      literature review. Secondary analysis of data was undertaken in a prospective
      cohort of women aged 40 and over, living in Leicestershire, UK. Subjects included
      3,411 women free from OAB at baseline and 277 incident cases of OAB. Reported
      diet, lifestyle, morbid, and social factors were measured at baseline and
      incident cases at 1-year follow-up. Graphical chain modeling was used to estimate
      the associations between variables and identify likely pathways involved.
      RESULTS: All hypothesized lifestyle factors (physical activity, high glycemic
      index, and high energy intake) plus diabetes and obesity were retained within the
      graph as potential contributors. However, low physical activity was the only
      direct risk factor linked prospectively to the onset of OAB (RR 2.47; 95% CI
      1.82, 3.36), in addition to older age. CONCLUSIONS: Poor lifestyle factors
      causally linked to diabetes and obesity may contribute to the onset of OAB; low
      physical activity appears to be an important modifiable causal factor for OAB
      operating directly as well as indirectly via pathways involving obesity or
      diabetes. Further research is needed to demonstrate a causal link between
      lifestyle and OAB.

PMID- 22374636
TI  - Breaking up prolonged sitting reduces postprandial glucose and insulin responses.
AB  - OBJECTIVE: Observational studies show breaking up prolonged sitting has
      beneficial associations with cardiometabolic risk markers, but intervention
      studies are required to investigate causality. We examined the acute effects on
      postprandial glucose and insulin levels of uninterrupted sitting compared with
      sitting interrupted by brief bouts of light- or moderate-intensity walking.
      RESEARCH DESIGN AND METHODS: Overweight/obese adults (n = 19), aged 45-65 years,
      were recruited for a randomized three-period, three-treatment acute crossover
      trial: 1) uninterrupted sitting; 2) seated with 2-min bouts of light-intensity
      walking every 20 min; and 3) seated with 2-min bouts of moderate-intensity
      walking every 20 min. A standardized test drink was provided after an initial 2-h
      period of uninterrupted sitting. The positive incremental area under curves
      (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink
      (75 g glucose, 50 g fat) were calculated for the respective treatments. RESULTS:
      The glucose iAUC (mmol/L) . h after both activity-break conditions was reduced
      (light: 5.2 [4.1-6.6]; moderate: 4.9 [3.8-6.1]; both P < 0.01) compared with
      uninterrupted sitting (6.9 [5.5-8.7]). Insulin iAUC (pmol/L) . h was also reduced
      with both activity-break conditions (light: 633.6 [552.4-727.1]; moderate: 637.6
      [555.5-731.9], P < 0.0001) compared with uninterrupted sitting (828.6 [722.0
      950.9]). CONCLUSIONS: Interrupting sitting time with short bouts of light- or
      moderate-intensity walking lowers postprandial glucose and insulin levels in
      overweight/obese adults. This may improve glucose metabolism and potentially be
      an important public health and clinical intervention strategy for reducing
      cardiovascular risk.

PMID- 22374637
TI  - Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post
      hoc epidemiologic analysis of the ACCORD trial.
AB  - OBJECTIVE: Self-management of type 2 diabetes including avoidance of hypoglycemia
      is complex, but the impact of cognition on safe self-management is not well
      understood. This study aimed to assess the effect of baseline cognitive function
      and cognitive decline on subsequent risk of severe hypoglycemia and to assess the
      effect of different glycemic strategies on these relationships. RESEARCH DESIGN
      AND METHODS: Prospective cohort analysis of data from the ACCORD trial included
      2,956 adults aged >=55 years with type 2 diabetes and additional cardiovascular
      risk factors. Cognitive tests (Digit Symbol Substitution Test [DSST], Rey
      Auditory Verbal Learning Test, Stroop Test, and Mini Mental Status Examination)
      were conducted at baseline and 20 months. Study outcomes were incident confirmed
      severe hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring
      any assistance (HAA). RESULTS: After a median 3.25-year follow-up, a 5-point
      poorer baseline score on the DSST was predictive of a first episode of HMA
      (hazard ratio 1.13 [95% CI 1.08-1.18]). Analyses of the other cognitive tests and
      of HAA were consistent with the DSST results. Cognitive decline over 20 months
      increased the risk of subsequent hypoglycemia to a greater extent in those with
      lower baseline cognitive function (P(interaction) = 0.037). Randomization to an
      intensive versus standard glycemic strategy had no impact on the relationship
      between cognitive function and the risk of severe hypoglycemia. CONCLUSIONS: Poor
      cognitive function increases the risk of severe hypoglycemia in patients with
      type 2 diabetes. Clinicians should consider cognitive function in assessing and
      guiding their patients regarding safe diabetes self-management regardless of
      their glycemic targets.

PMID- 22374638
TI  - Early retinal arteriolar changes and peripheral neuropathy in diabetes.
AB  - OBJECTIVE: To examine the association between early retinal arteriolar
      abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND
      METHODS: Data from 608 people (aged 40-80 years) with diabetes from the
      population-based Singapore Malay Eye Study were analyzed. Participants underwent
      binocular two-field digital retinal photography and quantitative sensory testing.
      DPN was defined as an abnormal response to a monofilament or neurothesiometer
      test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation
      geometry were measured using a computer-based program. Qualitative retinal signs
      of retinopathy and retinal arteriolar wall signs were graded by standardized
      methods. RESULTS: DPN was present in 155 people (25.5%). After adjusting for age,
      sex, diabetes duration, HbA(1c), cardiovascular risk factors, antihypertensive
      medication use, and peripheral arterial disease, people with suboptimal
      arteriolar caliber (odds ratio 1.94 [95% CI 1.22-3.10]), larger arteriolar
      branching coefficient (1.58 [1.03-2.42]), diabetic retinopathy (1.82 [1.20
      2.75]), and focal arteriolar narrowing (2.92 [1.48-5.76]) were more likely to
      have DPN. Participants with a greater number of retinal microvascular signs were
      more likely to have DPN than those without retinal changes (6.11 [2.11-17.71] for
      two or more signs and 3.47 [1.18-10.21] for one sign compared with none).
      CONCLUSIONS: Individuals with diabetes with early retinal arteriolar
      abnormalities are more likely to have DPN, independent of hyperglycemia and major
      vascular risk factors. These data support the hypothesis that early microvascular
      dysfunction, evident in the retina, is an independent risk factor for DPN.

PMID- 22374639
TI  - Effects of performing resistance exercise before versus after aerobic exercise on
      glycemia in type 1 diabetes.
AB  - OBJECTIVE: To determine the effects of exercise order on acute glycemic responses
      in individuals with type 1 diabetes performing both aerobic and resistance
      exercise in the same session. RESEARCH DESIGN AND METHODS: Twelve physically
      active individuals with type 1 diabetes (HbA(1c) 7.1 +/- 1.0%) performed aerobic
      exercise (45 min of running at 60% V(O(2peak))) before 45 min of resistance
      training (three sets of eight, seven different exercises) (AR) or performed the
      resistance exercise before aerobic exercise (RA). Plasma glucose was measured
      during exercise and for 60 min after exercise. Interstitial glucose was measured
      by continuous glucose monitoring 24 h before, during, and 24 h after exercise.
      RESULTS: Significant declines in blood glucose levels were seen in AR but not in
      RA throughout the first exercise modality, resulting in higher glucose levels in
      RA (AR = 5.5 +/- 0.7, RA = 9.2 +/- 1.2 mmol/L, P = 0.006 after 45 min of
      exercise). Glucose subsequently decreased in RA and increased in AR over the
      course of the second 45-min exercise bout, resulting in levels that were not
      significantly different by the end of exercise (AR = 7.5 +/- 0.8, RA = 6.9 +/-
      1.0 mmol/L, P = 0.436). Although there were no differences in frequency of
      postexercise hypoglycemia, the duration (105 vs. 48 min) and severity (area under
      the curve 112 vs. 59 units ? min) of hypoglycemia were nonsignificantly greater
      after AR compared with RA. CONCLUSIONS: Performing resistance exercise before
      aerobic exercise improves glycemic stability throughout exercise and reduces the
      duration and severity of postexercise hypoglycemia for individuals with type 1
      diabetes.

PMID- 22374640
TI  - Prevalence of prediabetes and diabetes and metabolic profile of patients with
      nonalcoholic fatty liver disease (NAFLD).
AB  - OBJECTIVE: Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be
      common and associated with a worse metabolic profile in patients with
      nonalcoholic fatty liver disease (NAFLD). However, no previous study has
      systematically screened this population. RESEARCH DESIGN AND METHODS: We studied
      the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients
      with NAFLD. The control group comprised 20 subjects without NAFLD matched for
      age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty
      acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by
      magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity
      (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin
      resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production
      * fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA *
      FPI). RESULTS: Prediabetes and T2DM was present in 85% versus 30% in controls (P
      < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were
      IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001).
      Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a
      similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR
      worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001)
      and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P <
      0.0001). CONCLUSIONS: Patients with NAFLD may benefit from early screening for
      T2DM, because the prevalence of abnormal glucose metabolism is much higher than
      previously appreciated. Regardless of glucose tolerance status, severe IR is
      common. In patients with T2DM, adipose tissue IR appears to play a major role in
      the severity of NAFLD.

PMID- 22374641
TI  - The association between IGF-I and insulin resistance: a general population study
      in Danish adults.
AB  - OBJECTIVE: IGF-I has an almost 50% amino acid sequence homology with insulin and
      elicits nearly the same hypoglycemic response. Studies showed that low and high
      IGF-I levels are related to impaired glucose tolerance and to a higher risk of
      type 2 diabetes. The aim of the current study was to evaluate the association
      between IGF-I level and insulin resistance in a Danish general population.
      RESEARCH DESIGN AND METHODS: Included were 3,354 adults, aged 19-72 years, from
      the cross-sectional Health2006 study. The homeostasis model assessment of insulin
      resistance (HOMA-IR) was used as the index to estimate insulin resistance. Serum
      IGF-I levels were determined by an immunoassay and grouped into quintiles (Q1
      Q5). Linear or multinomial logistic regression analyses were performed. RESULTS:
      In the study population, 520 subjects (15.5%) had increased HOMA-IR values above
      2.5. After adjustment for age, sex, physical activity, and waist-to-height ratio,
      a U-shaped association between IGF-I and HOMA-IR was found. Low IGF-I (Q1: odds
      ratio [OR] 1.65 [95% CI 1.16-2.34], P < 0.01) as well as high IGF-I (Q5: 1.96
      [1.38-2.79], P < 0.01) levels were related to a higher odds of increased HOMA-IR
      values compared with subjects with intermediate (Q3) IGF-I levels. These
      associations remained statistically significant after the exclusion of subjects
      with type 2 diabetes and by using the updated computer HOMA2-IR model.
      CONCLUSIONS: Low- and high-normal IGF-I levels are both related to insulin
      resistance. The biological mechanism of this complex phenomenon has to be
      elucidated in more detail for future risk stratification.

PMID- 22374642
TI  - The alteration of aspart insulin pharmacodynamics when mixed with detemir
      insulin.
AB  - OBJECTIVE: Mixing rapid acting insulin analogs with detemir insulin to minimize
      daily injections has been adopted as a common regimen, especially for some
      children with type 1 diabetes, despite the manufacturing company's caution
      against mixing these analogs in the same syringe. The effect of this practice on
      the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied.
      This crossover, randomized study was undertaken to determine whether mixing
      aspart with detemir insulin has an adverse effect on the early glucodynamic
      action of rapid-acting insulin analog in humans. RESEARCH DESIGN AND METHODS:
      Eight adolescents with type 1 diabetes (age 17.3 +/- 0.6 years and A1C 7.3 +/-
      0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4
      units/kg detemir insulin were injected either as a separate or single mixed
      injection in random order. RESULTS: Mixing the two insulins diminished the peak
      and overall early aspart insulin action with significantly lower maximum glucose
      infusion rate (GIR(max) separate 6.1 +/- 0.7 mg/kg/min vs. mix 4.5 +/- 0.5
      mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h
      of the insulin action study (separate 757 +/- 105 mg/kg vs. mix 491 +/- 66 mg/kg;
      P = 0.04). CONCLUSIONS: These data demonstrate that mixing aspart with detemir
      insulin markedly lowers the early PD action of aspart and prolongs its time
      action profile as compared with the separate injection of these analogs. These
      changes in insulin PD should be weighed against the added convenience of mixing
      when considering such unlicensed use of these insulins in youth with type 1
      diabetes.

PMID- 22374643
TI  - Prevalence of metabolic syndrome among an urban population in Kenya.
AB  - OBJECTIVE: Developing countries are undergoing an epidemiologic transition
      accompanied by increasing burden of cardiovascular disease (CVD) linked to
      urbanization and lifestyle modifications. Metabolic syndrome is a cluster of CVD
      risk factors whose extent in Kenya remains unknown. The aim of this study was to
      determine the prevalence of metabolic syndrome and factors associated with its
      occurrence among an urban population in Kenya. RESEARCH DESIGN AND METHODS: This
      was a household cross-sectional survey comprising 539 adults (aged >=18 years)
      living in Nairobi, drawn from 30 clusters across five socioeconomic classes.
      Measurements included waist circumference, HDL cholesterol, triacylglycerides
      (TAGs), fasting glucose, and blood pressure. RESULTS: The prevalence of metabolic
      syndrome was 34.6% and was higher in women than in men (40.2 vs. 29%; P < 0.001).
      The most frequently observed features were raised blood pressure, a higher waist
      circumference, and low HDL cholesterol (men: 96.2, 80.8, and 80%; women: 89.8,
      97.2, and 96.3%, respectively), whereas raised fasting glucose and TAGs were
      observed less frequently (men: 26.9 and 63.3%; women: 26.9 and 30.6%,
      respectively). The main factors associated with the presence of metabolic
      syndrome were increasing age, socioeconomic status, and education. CONCLUSIONS:
      Metabolic syndrome is prevalent in this urban population, especially among women,
      but the incidence of individual factors suggests that poor glycemic control is
      not the major contributor. Longitudinal studies are required to establish true
      causes of metabolic syndrome in Kenya. The Kenyan government needs to create
      awareness, develop prevention strategies, and strengthen the health care system
      to accommodate screening and management of CVDs.

PMID- 22374644
TI  - New insights from microcalorimetry on the FeOx/CNT-based electrocatalysts active
      in the conversion of CO2 to fuels.
AB  - Fe oxide nanoparticles show enhanced electrocatalytic performance in the
      reduction of CO(2) to isopropanol when deposited on an N-functionalized carbon
      nanotube (CNT) support rather than on a pristine or oxidized CNT support. XRD and
      high-resolution TEM were used to investigate the nanostructure of the
      electrocatalysts, and CO(2) adsorptive microcalorimetry was used to study the
      chemical nature of the interaction of CO(2) with the surface sites. Although the
      particles always present the same Fe(3)O(4) phase, their structural anisotropy
      and size inhomogeneity are consequences of the preparation method of the carbon
      surface. Two types of chemisorption sites have been determined by using
      microcalorimetry: irreversible sites (280 kJ mol(-1)) at the uncoordinated sites
      of the facets and reversible sites (120 kJ mol(-1)) at the hydrated oxide surface
      of the small nanoparticles. N-Functionalization of the carbon support is
      advantageous, as it causes the formation of small nanoparticles, which are highly
      populated by reversible chemisorbing sites. These characteristic features
      correlate with a higher electrocatalytic performance.

PMID- 22374645
TI  - The role of cognitive impairment in fall risk among older adults: a systematic
      review and meta-analysis.
AB  - BACKGROUND: cognitive impairment is an established fall risk factor; however, it
      is unclear whether a disease-specific diagnosis (i.e. dementia), measures of
      global cognition or impairments in specific cognitive domains (i.e. executive
      function) have the greatest association with fall risk. Our objective was to
      evaluate the epidemiological evidence linking cognitive impairment and fall risk.
      METHODS: studies were identified through systematic searches of the electronic
      databases of MEDLINE, EMBASE, PyschINFO (1988-2009). Bibliographies of retrieved
      articles were also searched. A fixed-effects meta-analysis was performed using an
      inverse-variance method. RESULTS: twenty-seven studies met the inclusion
      criteria. Impairment on global measures of cognition was associated with any
      fall, serious injuries (summary estimate of OR = 2.13 (1.56, 2.90)) and distal
      radius fractures in community-dwelling older adults. Executive function
      impairment, even subtle deficits in healthy community-dwelling older adults, was
      associated with an increased risk for any fall (summary estimate of OR = 1.44
      (1.20, 1.73)) and falls with serious injury. A diagnosis of dementia, without
      specification of dementia subtype or disease severity, was associated with risk
      for any fall but not serious fall injury in institution-dwelling older adults.
      CONCLUSION: the method used to define cognitive impairment and the type of fall
      outcome are both important when quantifying risk. There is strong evidence global
      measures of cognition are associated with serious fall-related injury, though
      there is no consensus on threshold values. Executive function was also associated
      with increased risk, which supports its inclusion in fall risk assessment
      especially when global measures are within normal limits.

PMID- 22374646
TI  - Temporal relationship between handgrip strength and cognitive performance in
      oldest old people.
AB  - BACKGROUND: cognitive decline and muscle weakness are prevalent health conditions
      in elderly people. We hypothesised that cognitive decline precedes muscle
      weakness. OBJECTIVE: to analyse the temporal relationship between cognitive
      performance and handgrip strength in oldest old people. DESIGN: prospective
      population-based 4-year follow-up study. SUBJECTS: a total of 555 subjects, all
      aged 85 years at baseline, were included into the study. METHODS: handgrip
      strength measured at age 85 and 89 years. Neuropsychological test battery to
      assess global cognitive performance, attention, processing speed and memory at
      baseline and repeated at age 89 years. Associations between handgrip strength and
      cognitive performance were analysed by repeated linear regression analysis
      adjusted for common confounders. RESULTS: at age 85 and 89 years, better
      cognitive performance was associated with higher handgrip strength (all, P<0.03),
      except for attention. There was no longitudinal association between baseline
      handgrip strength and cognitive decline (all, P>0.10), except for global
      cognitive performance (P=0.007). Better cognitive performance at age 85 years was
      associated with slower decline in handgrip strength (all, P<0.01) after
      adjustment for common confounders. CONCLUSION: baseline cognitive performance was
      associated with decline in handgrip strength, whereas baseline handgrip strength
      was not associated with cognitive decline. Our results suggest that cognitive
      decline precedes the onset of muscle weakness in oldest old people.

PMID- 22374647
TI  - The birth of the lithium-ion battery.

PMID- 22374648
TI  - pi-Electron-system-layered polymer: through-space conjugation and properties as a
      single molecular wire.
AB  - [2.2]Paracyclophane-based through-space conjugated oligomers and polymers were
      prepared, in which poly(p-arylene-ethynylene) (PAE) units were partially pi
      stacked and layered, and their properties in the ground state and excited state
      were investigated in detail. Electronic interactions among PAE units were
      effective through at least ten units in the ground state. Photoexcited energy
      transfer occurred from the stacked PAE units to the end-capping PAE moieties. The
      electrical conductivity of the polymers was estimated using the flash-photolysis
      time-resolved microwave conductivity (FP-TRMC) method and investigated together
      with time-dependent density functional theory (TD-DFT) calculations, showing that
      intramolecular charge carrier mobility through the stacked PAE units was a few
      tens of percentage larger than through the twisted PAE units.

PMID- 22374649
TI  - Ultra-small-angle X-ray scattering-X-ray photon correlation spectroscopy studies
      of incipient structural changes in amorphous calcium phosphate-based dental
      composites.
AB  - The local structural changes in amorphous calcium phosphate (ACP)-based dental
      composites were studied under isothermal conditions using both static, bulk
      measurement techniques and a recently developed methodology based on combined
      ultra-small angle X-ray scattering-X-ray photon correlation spectroscopy (USAXS
      XPCS), which permits a dynamic approach. While results from conventional bulk
      measurements do not show clear signs of structural change, USAXS-XPCS results
      reveal unambiguous evidence for local structural variations on a similar time
      scale to that of water loss in the ACP fillers. A thermal-expansion-based
      simulation indicates that thermal behavior alone does not account for the
      observed dynamics. Together, these results suggest that changes in the water
      content of ACP affect the composite morphology due to changes in ACP structure
      that occur without an amorphous-to-crystalline conversion. It is also noted that
      biomedical materials research could benefit greatly from USAXS-XPCS, a dynamic
      approach.

PMID- 22374650
TI  - Braces for the peptide backbone: insights into structure-activity relationships
      of protease inhibitor mimics with locked amide conformations.

PMID- 22374651
TI  - Combined magnitude and phase-based segmentation of the cerebral cortex in 7T MR
      images of the elderly.
AB  - PURPOSE: To propose a new method that integrates both magnitude and phase
      information obtained from magnetic resonance (MR) T*(2) -weighted scans for
      cerebral cortex segmentation of the elderly. MATERIALS AND METHODS: This method
      makes use of K-means clustering on magnitude and phase images to compute an
      initial segmentation, which is further refined by means of transformation with
      reconstruction criteria. The method was evaluated against the manual segmentation
      of 7T in vivo MR data of 20 elderly subjects (age = 67.7 +/- 10.9). The added
      value of combining magnitude and phase was also evaluated by comparing the
      performance of the proposed method with the results obtained when limiting the
      available data to either magnitude or phase. RESULTS: The proposed method shows
      good overlap agreement, as quantified by the Dice Index (0.79 +/- 0.04), limited
      bias (average relative volume difference = 2.94%), and reasonable volumetric
      correlation (R = 0.555, p = 0.011). Using the combined magnitude and phase
      information significantly improves the segmentation accuracy compared with using
      either magnitude or phase. CONCLUSION: This study suggests that the proposed
      method is an accurate and robust approach for cerebral cortex segmentation in
      datasets presenting low gray/white matter contrast.

PMID- 22374652
TI  - Screening for obstructive sleep apnea in Treacher-Collins syndrome.
AB  - OBJECTIVES/HYPOTHESIS: This study evaluated the accuracy of established
      obstructive sleep apnea syndrome (OSAS) questionnaires based on presenting
      symptoms and complaints as screening tools for OSAS in Treacher-Collins syndrome
      (TCS). STUDY DESIGN: Cross-sectional cohort study. METHODS: In 35 TCS patients
      (13 children, 22 adults) in whom diagnostic polysomnographic results on OSAS were
      available, the Brouillette score was evaluated in children and the Epworth
      Sleepiness Scale in adults. RESULTS: The total Brouillette score showed a
      sensitivity of 50%, specificity of 71%, and positive and negative predictive
      values of 60% and 63%, respectively. The answer "No" to the question as to
      whether a child snored could rule out OSAS in children, and showed positive and
      negative predictive values of 55% and 100%, respectively. The Epworth Sleepiness
      Scale showed a sensitivity of 0%, specificity of 92%, and positive and negative
      predictive values of 0% and 57%, respectively. A positive answer to the question
      of whether a person falls asleep while sitting and talking to someone (sometimes
      or more) was able to predict OSAS in adults; this question had positive and
      negative predictive values of 100% and 72%, respectively. CONCLUSIONS: This cross
      sectional cohort study showed that the Brouillette score and the Epworth
      Sleepiness Scale are of minimal usefulness in TCS. Diagnosis of OSAS based solely
      on complaints is not reliable, probably due to habituation. Therefore, for a good
      evaluation and optimal multidisciplinary treatment of this chronic disease in
      TCS, all newly referred pediatric and adult TCS patients should be screened for
      OSAS at least once with polysomnography.

PMID- 22374653
TI  - TALK score: Development and validation of a prognostic model for predicting
      larynx preservation outcome.
AB  - OBJECTIVES/HYPOTHESIS: To develop and validate a simple prognostic tool that
      would help predict larynx preservation outcome. STUDY DESIGN: A retrospective
      review of 3 prospective studies. METHODS: We reviewed consecutive
      chemotherapy/radiation protocols for patients (n = 170) with advanced,
      resectable, squamous cell, larynx, or pharynx cancer treated at Memorial Sloan
      Kettering Cancer Center from 1988 to 1995 with larynx preservation intent. The
      outcome was successful larynx preservation. Model validation used data from U. S.
      Department of Veterans Affairs larynx preservation study. RESULTS: The developed
      model added one point for each poor prognostic covariate present (show in
      parentheses) and was given the acronym TALK: T stage (T4), albumin (<4 g/dL),
      maximum alcohol/liquor use (>=6 drinks/day or heavy drinking), and Karnofsky
      performance status (<80%). The 3-year larynx preservation rates by TALK score
      were 65% (0), 41% (1-2), and 6% (3-4), P < .0001; on validation, the TALK 3-4
      group was particularly well demarcated. CONCLUSIONS: The TALK score is an easily
      applied and valid tool that should assist treatment selection.

PMID- 22374654
TI  - [Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis  (PFAPA
      syndrome) in adults].
AB  - BACKGROUND AND OBJECTIVE: The PFAPA syndrome is characterized by a regular
      appearance of periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenitis and is associated with a distinctive poor general condition of the
      patients. Since its first description in 1987 the syndrome has usually been
      described in children. But we here report its diagnosis in three adult patients.
      METHODS: At the Department of Otorhinolaryngology/Head and Neck Surgery of the
      University Medical Center Freiburg, data on 36 patients with PFAPA syndrome were
      collected between 2004 and 2010.  Data analysis was based on structured
      questionnaires, medical files of patients and a systematic assessment of the
      relevant international literature up to April 2011. RESULTS: The average age of
      the initial occurrence of PFAPA syndrome in the three patients was in the first
      few months after birth (month 2, 6 and 7). A tonsillectomy had been performed on
      all three patients in early childhood. As a result two patients had remission of
      symptoms for several years (4.5 and 12 years) with recurrence of PFAPA attacks
      while the third patient had no changes in symptoms. CONCLUSION: The PFAPA
      syndrome is an illness that first manifests itself in children. However, it can
      persist until adulthood or reappear after phases of remission. A knowledge of
      this periodic fever syndrome and extensive and close cooperation of general
      practitioners, paediatricians, internists and ENT specialists will be helpful in
      early diagnosis of this disorder.

PMID- 22374655
TI  - [De novo sarcoidosis after kidney transplantation].
AB  - HISTORY AND CLINICAL FINDINGS: A 39-year-old man complained of unspecific chest
      pains four years after kidney transplantation. INVESTIGATIONS: Laboratory tests
      revealed a slow increase of retentions values; the value of soluble IL-2 receptor
      was slightly elevated. Computed tomography of the chest confirmed mediastinal and
      bilateral hilar masses. The broncho-alveolar lavage (BAL) showed a marked
      increase of the CD4/CD8 T-lymphocyte ratio and the aspiration cytology of these
      lymphadenopathies revealed the cytopathological characteristics of sarcoidosis.
      TREATMENT AND CLINICAL COURSE: An asymptomatic stage I sarcoidosis was diagnosed,
      and the immunosuppressive treatment with cyclosporine, mycophenolatmofetil and
      prednisone was retained. The patient has remained asymptomatic for now six
      months. CONCLUSION: When bilateral hilar / mediastinal lymphadenopathies occur
      after organ transplantation with immunosuppression de novo sarcoidosis should be
      taken into account.

PMID- 22374656
TI  - [44-year-old man with minor bleeding tendency].

PMID- 22374657
TI  - [Malignant pleural mesothelioma].
AB  - Malignant pleural mesothelioma (MMP) is a highly aggressive tumor arising of the
      pleural mesothelium. Asbestos exposure is the main factor involved in the
      pathogenesis of MMP and according to the late ban of this agent in 2005 the peak
      incidence in Europe is expected in the next twenty years. The highly aggressive
      behaviour of this tumor results in a poor prognosis with a mean overall survival
      between 7 and 9 months. Despite the progress made in diagnosis and therapy of
      this entity the optimal treatment remains a subject of debate. In this article we
      review the current state of treatment and diagnosis.

PMID- 22374658
TI  - [Living wills under close scrutiny: Medical consultation is indispensable].
AB  - Since September 2009 the handling of living wills has been regulated by law. Even
      though a medical consultation is not imperative for the drawing up of a living
      will, first surveys have shown that medical information about clinical pictures
      and treatment options lead to an important specification of living wills. For the
      first time in Germany, a questionnaire has been developed to investigate the
      impact of medical consultations on the content of living wills. It revealed that
      nearly all the people surveyed who had already drawn up a living will wished to
      change the content of their completed will after attending the seminar because
      the previous version was no longer in accordance with their wishes. In the light
      of the frequent difficulties in hospitals concerning how to apply a living will
      to an actual clinical situation, we believe structured medical consultations to
      be indispensable.

PMID- 22374659
TI  - [Friend or Foe?--Psoriasin and Koebnerisin: multifunctional defence molecules in
      skin differentiation, tumorigenesis and inflammation].
AB  - Psoriasin (S100A7) and koebnerisin (S100A15) were first identified in inflamed
      psoriatic skin. They have lately evolved by gene duplications within the
      Epidermal Differentiation Complex (chromosome 1q21) and form a novel S100
      subfamily in human. Despite highest homology (>  90 %), psoriasin and koebnerisin
      are distinct in tissue distribution, regulation, and function. They act
      differently as antimicrobial peptides (AMP) and synergize to promote inflammation
      and cell migration as endogenous danger signals ("alarmines") and
      chemoattractants. Their different properties are compelling reasons to
      discriminate psoriasin and koebnerisin in epithelial homeostasis, inflammation
      and epithelial carcinogenesis.

PMID- 22374660
TI  - [Allogeneic stem cell transplantation for acute myeloid leukemia and HIV
      infection--case 3/2012].
AB  - HISTORY AND ADMISSION FINDINGS: A 27-year-old male patient with a past medical
      history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic
      stem cell transplantation (HSCT). Highly active anti-retroviral therapy
      suppressed the viral load below detection threshold. INVESTIGATIONS: There were
      no contraindications for allogeneic HSCT. TREATMENT AND COURSE: Myeloablative
      conditioning consisted of total body irradiation and cyclophosphamide. Anti
      thymocyte globulin, tacrolimus and mycophenolate mofetil were used for
      immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide
      analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc
      and raltegravir) was maintained for allogeneic HSCT and viral load remained below
      detection threshold. No graft-versus-host disease or serious infectious
      complications occurred. The patient showed good graft function with stable
      hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after
      allogeneic HSCT and treated successfully with surgical excision and reduction of
      immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is
      rising and viral load remains below detection threshold with combined anti
      retroviral therapy. CONCLUSION: Allogeneic HSCT can be safely performed in HIV
      positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and
      linked to strong immunosuppression.

PMID- 22374661
TI  - [Cut a long story too short: Challenges in clinical research].
AB  - Clinical research reflects a mandatory prerequisite to translate basic research
      into clinical practice. While a lack of available qualified doctors to fill
      positions in hospitals as well as in the ambulant sector has prompted political
      decisions to counteract, Germany has witnessed an insidious deterioration of
      clinical research over time and compared to other industrialized countries.
      Measures to prevent an increasing loss of academic profile have to tackle all
      aspects from undergraduate to postgraduate training to attract highly skilled
      doctors in sustainable structures to reflourish academic medicine. Cornerstones
      to achieve these goals involve establishing of structured graduate programs,
      acknowledgment of time spend in clinical research in residency programs, extra
      occupational opportunities to achieve dual qualification (e. g. Master programs
      in clinical research) as well as independent positions with inherent carrier
      perspectives in academic medicine for doctors interested in clinical and
      translational research.

PMID- 22374662
TI  - A TORway to osteolytic disease.

PMID- 22374663
TI  - Emerging targets for the prevention of pregnancy-associated breast cancer.

PMID- 22374664
TI  - Sumoylation fights "aggregopathies".

PMID- 22374665
TI  - The aryl hydrocarbon receptor as a promoter of malignant glioma.

PMID- 22374666
TI  - Micronucleophagy: a new mechanism to protect against chromosomal instability?

PMID- 22374667
TI  - TRIM8 and p53: making the right decision.

PMID- 22374668
TI  - Sgo1 as a "guardian spirit" for preventing colon tumorigenesis.

PMID- 22374669
TI  - Sgo1 as a guardian of chromosome stability.

PMID- 22374670
TI  - EDD induces cell cycle arrest by increasing p53 levels.
AB  - Tight regulation of p53 is essential for its central role in maintaining genome
      stability and tumor prevention. Here, EDD/ UBR5/hHyd, hereafter called EDD, is
      identified as a novel regulator of p53. Downregulation of EDD results in elevated
      p53 protein levels both in transformed and untransformed cells. Concomitant with
      a rise in p53, the levels of p21, a critical p53 target, are also elevated in
      these conditions. Surprisingly, EDD knockdown does not affect p53 protein
      stability, and p53 mRNA levels do not increase significantly upon EDD depletion.
      Consistent with the function of p53, EDD downregulation triggers a senescent
      phenotype in fibroblasts at later time points. In addition, the increased p53
      levels upon EDD depletion cause a G(1) arrest, as co-depletion of EDD and p53
      completely rescues this effect on cell cycle progression.

PMID- 22374671
TI  - The STAT3-IGFBP5 axis is critical for IL-6/gp130-induced premature senescence in
      human fibroblasts.
AB  - Cells undergo senescence in response to various conditions, including telomere
      erosion, oncogene activation and multiple cytokines. One of these cytokines,
      interleukin-6 (IL-6), not only functions in the immune system, but also promotes
      cellular senescence and cancer. Here we demonstrate that IL-6 and the soluble IL
      6 receptor (sIL-6R) induce premature senescence in normal human fibroblasts by
      establishing a senescence-inducing circuit involving the signal transducer and
      activator of transcription 3 (STAT3) and insulin-like growth factor-binding
      protein 5 (IGFBP5). Stimulating TIG3 fibroblast cells with IL-6/sIL-6R
      sequentially caused an increase in reactive oxygen species (ROS) as early as day
      1, followed by the DNA damage response, p53 accumulation and, finally, senescence
      on days 8-10. We found that STAT3 was required for the events leading to
      senescence, including the initial early-phase ROS increase and the induction of
      IL-1alpha/beta, IL-6 and CXCL8 mRNAs 4-5 d after IL-6/sIL-6R stimulation,
      suggesting that STAT3's role is indirect. We searched for STAT3-downstream
      molecule(s) responsible for the senescence-inducing activity in the supernatants
      of stimulated TIG3 and identified IGFBP5 as a major STAT3 mediator, because
      IGFBP5 was expressed from the early phase through the entire senescence process
      and was responsible for IL-6/STAT3-induced ROS increase and premature senescence.
      Thus, IL-6/sIL-6R forms a senescence-inducing circuit involving the STAT3-IGFBP5
      axis as a key triggering and reinforcing component.

PMID- 22374672
TI  - MDM4 enhances p53 stability by promoting an active conformation of the protein
      upon DNA damage.
AB  - Stabilization of p53 protein is an important step in the activation of its
      function. p53 levels are regulated by ubiquitin-dependent and -independent
      degradation pathways. MDM4 (MDMX) is an important regulator of p53, able to both
      stimulate and antagonize p53 degradation. Both of these activities have been
      attributed to the ability of MDM4 to potentiate or antagonize the function of
      MDM2, the main ubiquitin ligase of p53, depending on their relative levels. Here,
      we have investigated the stabilizing function of endogenous MDM4 using genetic
      models of knockout MEFs and RNA interference in human non-transformed cell lines.
      Our data demonstrate that MDM4 is able to stabilize p53, protecting it from
      proteasome-mediated degradation in a MDM2- and ubiquitin-independent manner. Upon
      DNA damage, MDM4 is associated to p53 independently of MDM2 and promotes a
      conformational change of the protein toward an active form. This correlates with
      a decreased association of p53 to the proteasome and increased protein levels.
      The association between MDM4 and p53 is evidenced in the cytoplasmic compartment,
      supporting the role of cytoplasmic stabilization of p53 during its activation.
      This work demonstrates that the ability of MDM4 to enhance p53 stability is
      actually a specific property of MDM4 accomplished upon DNA damage. In addition,
      these data support the hypothesis of distinct functions of MDM4 under different
      growth conditions.

PMID- 22374673
TI  - Mimosine arrests the cell cycle prior to the onset of DNA replication by
      preventing the binding of human Ctf4/And-1 to chromatin via Hif-1alpha activation
      in HeLa cells.
AB  - Though the G(1) checkpoint in mammalian cells has been known for decades, the
      molecular targets that prevent S-phase entry remain unknown. Mimosine is a rare
      plant amino acid that arrests the cell cycle in the G(1) phase before entry into
      S phase. Here, we show that mimosine interrupts the binding of Ctf4 to chromatin,
      which is essential for the initiation of DNA replication in HeLa cells, and this
      effect is mediated by the Hif-1alpha-dependent increase in the level of p27.
      Depletion of Hif-1alpha results in an increased binding of Ctf4 to chromatin and
      the entry of cells into S phase even in the presence of mimosine. These results
      suggest that the binding of Ctf4 to chromatin is the target of the Hif-1alpha
      dependent checkpoint pathway for cell cycle arrest in G(1) phase. Although we
      observed Hif-1alpha-dependent arrest in mimosine-treated cells, it is possible
      that Ctf4 may act as a common target for G(1) arrest in various other checkpoint
      pathways.

PMID- 22374674
TI  - MicroRNA-143 is a critical regulator of cell cycle activity in stem cells with co
      overexpression of Akt and angiopoietin-1 via transcriptional regulation of
      Erk5/cyclin D1 signaling.
AB  - We report that simultaneous expression of Akt and angiopoietin-1 (Ang-1)
      transgenes supported mitogenesis in stem cells with a critical role for microRNA
      143 (miR-143) downstream of FoxO1 transcription factor. Mesenchymal stem cells
      (MSC) from young male rats were transduced with Ad-vectors encoding for Akt
      ((Akt)MSC) and Ang-1 ((Ang-1)MSC) transgenes for their individual or simultaneous
      overexpression ((AA)MSC; > 5-fold gene level and > 4-fold Akt and Ang-1 protein
      expression in (AA)MSC vs. Ad-Empty transduced MSC; (Emp)MSC). (AA)MSC had higher
      phosphorylation of FoxO1, which activated Erk5, a distinct mitogen-induced MAPK
      that drove transcriptional activation of cyclin D1 and Cdk4. Flow cytometry
      showed > 10% higher S-phase cell population that was confirmed by BrdU assay
      (15%) and immunohistology for Ki67 (11%) in (AA)MSC using (Emp)MSC as controls.
      miR array supported by real-time PCR showed induction of miR-143 in (AA)MSC (4.73
      fold vs.. (Emp)MSC). Luciferase assay indicated a dependent relationship between
      miR-143 and Erk5 in (AA)MSC. FoxO1-specific siRNA upregulated miR-143, whereas
      inhibition of miR-143 did not change FoxO1 activation. However, miR-143
      inhibition repressed phosphorylation of Erk5 and abrogated cyclin D1 with
      concomitant reduction in cells entering cell cycle. During in vivo studies, male
      GFP+ (AA)MSC transplanted into wild-type female infarcted rat hearts showed
      significantly higher number of Ki67 expressing cells (p < 0.05 vs. (Emp)MSC) 7
      days after engraftment (n = 4 animals/group). In conclusion, co-overexpression of
      Akt and Ang-1 in MSC activated cell cycle progression by upregulation of miR-143
      and stimulation of FoxO1 and Erk5 signaling.

PMID- 22374675
TI  - Inactivation of Pmc1 vacuolar Ca(2+) ATPase causes G(2) cell cycle delay in
      Hansenula polymorpha.
AB  - The vacuolar Ca(2+) ATPase Pmc1 is involved in maintenance of a low Ca(2+)
      concentration in cytosol in yeast cells. Here we observed that increase of Ca(2+)
      cytosolic concentration in yeast Hansenula polymorpha due to inactivation of Pmc1
      resulted in sensitivity to sodium dodecyl sulfate (SDS). To elucidate the
      mechanisms of the observed effect, a screening for mutations suppressing SDS
      sensitivity of the H. polymorpha pmc1 mutant was performed. As a result, three
      genes were identified. Two of them, designated as their Saccharomyces cerevisiae
      orthologs CCH1 and HOG1 encoded the plasma membrane voltage-gated high-affinity
      calcium channel and the MAP kinase involved in osmoregulation, respectively. The
      third gene, designated as WEE1, coded for the ortholog of Wee1/Swe1 kinase
      involved in cell cycle regulation by inhibiting of the G(2)/M transition.
      Detailed analysis of this mutant demonstrated that suppression of pmc1 SDS
      sensitivity by the wee1 mutation depended on an accompanying chromosomal
      rearrangement, whereas inactivation of WEE1 in the absence of this rearrangement
      caused SDS sensitivity. Expression of a chimeric protein containing an N-terminal
      portion of Wee1 in the pmc1 mutant led to abnormal morphology characteristic of
      G(2) delay. Our data indicate that cytosolic Ca(2+) rise causes SDS sensitivity
      in H. polymorpha through the activation of the Wee1 kinase, which is mediated by
      the Hog1 kinase. Wee1 has a dual role in the manifestation of SDS sensitivity in
      the H. polymorpha pmc1 mutant. Mechanisms of influence of the obtained mutations
      on the G(2)/M transition are discussed.

PMID- 22374676
TI  - MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by
      directly targeting PTEN.
AB  - Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but
      radioresistance severely reduces NPC radiocurability. Here, we have established a
      radio-resistant NPC cell line, CNE-2R, and investigate the role of miRNAs in
      radioresistance. The miRNAs microarray assay reveals that miRNAs are
      differentially expressed between CNE-2R and its parental cell line CNE-2. We find
      that miR-205 is elevated in CNE-2R. A target prediction algorithm suggests that
      miR-205 regulates expression of PTEN, a tumor-suppressor. Introducing miR-205
      into CNE-2 cells suppresses PTEN protein expression, followed by activation of
      AKT, increased number of foci formation and reduction of cell apoptosis
      postirradiation. On the other hand, knocking down miR-205 in CNE-2R cells
      compromises the inhibition of PTEN and increases cell apoptosis. Significantly,
      immunohistochemistry studies demonstrate that PTEN is downregulated at late
      stages of NPC, and that miR-205 is significantly elevated followed the
      radiotherapy. Our data conclude that miR-205 contributes to radioresistance of
      NPC by directly targeting PTEN. Both miR-205 and PTEN are potential predictive
      biomarkers for radiosensitivity of NPC and may serve as targets for achieve
      successful radiotherapy in NPC.

PMID- 22374678
TI  - Women with pure stress urinary incontinence symptoms assessed by the initial
      standard evaluation including measurement of post-void residual volume and a
      stress test: are urodynamic studies still needed?
AB  - AIMS: The significance of preoperative urodynamic studies in women with a
      "clinically-defined pure stress urinary incontinence (SUI) symptom" has been
      debated in recent years. We evaluated changes of reliability of pure SUI symptoms
      for prediction of pure urodynamic SUI (USUI) when the assessment of post-void
      residual (PVR) volume and a stress test, designated as the initial standard
      evaluation in the NICE and AUA guidelines, were added to the process for the
      diagnosis of pure SUI symptoms. METHODS: We reviewed records of 1,019 women aged
      30-80 who underwent urodynamic study for incontinence. Criteria for pure SUI
      symptoms were defined as absence of overactive bladder symptoms and voiding
      difficulties based on a frequency-volume chart and AUA Symptom Index. We then
      added assessment of PVR volume and a stress test to the process for clinical
      diagnosis. RESULTS: Of subjects, 211 (20.7%) could be classified as having a pure
      SUI symptom. Of these, only 167 (79.1%) had pure USUI and 33 (15.7%) had detrusor
      overactivity. Eight (3.8%) had detrusor underactivity/bladder outlet obstruction.
      Sensitivity and specificity of pure SUI symptoms for pure USUI were 28.6% and
      89.9%. Addition of assessment of PVR volume and a stress test resulted in an
      increase of predictive accuracy of only 3.6%. CONCLUSIONS: As one-fifth of women
      with pure SUI symptoms exhibit the pathophysiologies that could affect the
      surgical outcomes despite additional use of PVR assessment and a stress test in
      the clinical diagnostic process, urodynamic evaluation is considered necessary
      before anti-incontinence surgery in this population.

PMID- 22374677
TI  - Sumoylated BubR1 plays an important role in chromosome segregation and mitotic
      timing.
AB  - BubR1 is an important component of the spindle assembly checkpoint, and
      deregulated BubR1 functions frequently result in chromosomal instability and
      malignant transformation. We recently demonstrated that BubR1 was modified by
      sumoylation, and that lysine 250 (K250) functions as the crucial site for this
      modification. BubR1 sumoylation was neither required for its activation nor for
      binding to kinetochores. However, ectopically expressed sumoylation-deficient
      BubR1 mutants were retained on the kintochores even after apparent chromosome
      congression. The kinetochore retention of the sumoylation-deficient mutant of
      BubR1 caused an anaphase delay coupled with premature sister chromatid
      separation. Moreover, BubR1 interacted with unphosphorylated Sgo1, and its
      sumoylation facilitated the interaction. BubR1 sumoylation was inversely
      associated with its acetylation during mitotic progression. Trichostatin A, a
      protein deacetylase inhibitor, significantly compromised BubR1 sumoylation.
      Combined, these results reveal that BubR1 sumoylation plays an important role in
      its timely removal from the kinetochores and the checkpoint inactivation, thus
      allowing normal anaphase entry and chromosome segregation.

PMID- 22374679
TI  - Disposition of opioids in oral fluid: Importance of chromatography and mass
      spectral transitions in LC-MS/MS.
AB  - The use of prescription pain relievers, specifically opioids, has been increasing
      over the last few years. Oral fluid is easier to collect than urine, is difficult
      to adulterate, and is a reflection of free drug in the body, so its analysis is
      becoming more widespread in the monitoring of opioids. The demethylated
      metabolites of oxycodone, hydrocodone, and codeine are present at higher
      concentrations in oral fluid than oxymorphone, hydromorphone, and morphine,
      respectively; therefore, their detection in saliva indicates ingestion of the
      medication rather than diversion, and should be included in the analysis of
      opioids in this matrix. Since the compounds have the same nominal molecular
      weights, the same M + H(+) precursor ions in positive electrospray mode, and
      potentially identical collisionally activated fragmentation patterns, the
      importance of chromatography to separate the various opioids as well as the
      selection of mass spectral transitions is critical for correct identification. A
      procedure for the simultaneous determination of 12 opioid related compounds in
      oral fluid using liquid chromatography with tandem mass spectrometry (LC-MS/MS)
      is presented. The recovery of opioids from the collection device was over 80% at
      20 ng/ml; intra-day imprecision was less than 6.8%; inter-day imprecision less
      than 6.2%. In authentic specimens, the predominant metabolite of oxycodone was
      noroxycodone; for specimens containing codeine, no morphine was detected; and for
      hydrocodone positives, norhydrocodone was detected at significantly higher levels
      than hydromorphone. The importance of monitoring specific mass spectral
      transitions and chromatographic separation is demonstrated.

PMID- 22374680
TI  - Hydrogenolysis goes bio: from carbohydrates and sugar alcohols to platform
      chemicals.
AB  - In view of the diminishing oil resources and the ongoing climate change, the use
      of efficient and environmentally benign technologies for the utilization of
      renewable resources has become indispensible. Therein, hydrogenolysis reactions
      offer a promising possibility for future biorefinery concepts. These reactions
      result in the cleavage of C-C and C-O bonds by hydrogen and allow direct access
      to valuable platform chemicals already integrated in today's value chains. Thus,
      hydrogenolysis bears the potential to bridge currently available technologies and
      future biomass-based refinery concepts. This Review highlights past and present
      developments in this field, with special emphasis on the direct utilization of
      cellulosic feedstocks.

PMID- 22374681
TI  - Validating the clinical assessment of eustachian tube dysfunction: The Eustachian
      Tube Dysfunction Questionnaire (ETDQ-7).
AB  - OBJECTIVES/HYPOTHESIS: Eustachian tube dysfunction (ETD) is a common condition
      that is associated with otologic and rhinologic symptoms. The complete assessment
      of ETD is limited without a valid symptom score. We developed and conducted
      initial validation of the seven-item Eustachian Tube Dysfunction Questionnaire
      (ETDQ-7), a disease-specific instrument to assess symptoms with respect to ETD.
      STUDY DESIGN: Validation study. METHODS: The ETDQ-7 was developed using standard
      survey methodology. The ETDQ-7 was completed by a group of 50 consecutive adult
      patients diagnosed with ETD and 25 non-ETD patients who served as a control
      group. Tympanometry was used as a criterion standard to distinguish the two
      groups. A subset of respondents repeated the ETDQ-7 at a time point 4 weeks
      later. RESULTS: Content validity for the ETDQ-7 was established by focus group
      and review of the literature. Reliability testing indicated acceptable internal
      consistency for the entire instrument (Cronbach alpha = .71). The test-retest
      reliability indicated good correlation between the two questionnaires completed
      by the same patient 4 weeks apart (r = 0.78). The ETDQ-7 was able to discriminate
      between patients with ETD and those without (P < .001), indicating excellent
      discriminant validity. CONCLUSIONS: The ETDQ-7 is a valid and reliable symptom
      score for use in adult patients with ETD that may facilitate clinical practice by
      highlighting the impact of ETD. Further testing is needed to determine its
      usefulness in assessing treatment response.

PMID- 22374682
TI  - Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel
      system.
AB  - A novel composite material consisting of a silica aerogel core coated by a
      poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel
      composite as a drug delivery system was tested with ketoprofen as a model drug
      due to its solubility in supercritical carbon dioxide. The results indicated that
      both drug loading capacity and drug release profiles could be tuned by changing
      hydrophobicity of aerogels, and that drug loading capacity increased with
      decreased hydrophobicity, while slower release rates were achieved with increased
      hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the
      prepolymer solution of the hydrogel coating delayed the release of the drug which
      can be attributed to the lower permeability at higher PEG diacrylate
      concentrations. The novel composite developed in this study can be easily
      implemented to achieve the controlled delivery of various drugs and/or proteins
      for specific applications.

PMID- 22374683
TI  - Aryl ether as a Negishi coupling partner: an approach for constructing C-C bonds
      under mild conditions.
AB  - An etheric Negishi coupling: The first cross-coupling reaction between aryl alkyl
      ethers and dianion-type zincate reagents to afford biaryl compounds through
      selective cleavage of the etheric C(sp(2))-O bond was developed. Dianion-type
      zincates showed excellent reactivity toward the aromatic ethers under mild
      conditions, with good functional group compatibility (see scheme).

PMID- 22374684
TI  - Accuracy of pneumonia hospital admissions in a primary care electronic medical
      record database.
AB  - PURPOSE: When using electronic medical record data to study drug use,
      hospitalizations are markers of severe outcomes. To identify events within a
      specified time window, it is important to validate hospitalization diagnoses and
      dates. Our objective was to validate pneumonia hospitalizations and their dates
      identified using hospitalization codes in The Health Improvement Network (THIN),
      a UK primary care electronic medical record. METHODS: This cross-sectional study
      used a cohort of THIN adult visits for acute nonspecific respiratory infections
      from June 1985 to August 2006. Pneumonia hospitalizations within 30 days after
      the visit were identified using THIN diagnosis and hospitalization codes; 60
      participants were randomly selected for validation. Patients' general
      practitioners (GPs) returned de-identified hospital summaries and consultants'
      letters regarding overnight hospitalizations within a 180-day window around the
      THIN hospitalization. Positive predictive value (PPV) was the number of GP
      validated hospitalizations divided by THIN documented hospitalizations. RESULTS:
      GPs returned 59 of 60 patient records; 52 had confirmed hospitalizations. PPV of
      THIN hospitalization documentation was 88% (95%CI = 77-95). One admission was not
      for pneumonia; PPV of THIN-documented pneumonia admission was 86% (95%CI = 75
      94). Of 52 valid THIN hospitalizations, 50 were actually admitted within 14 days
      of the documented THIN date (range = -2 to +18). The absolute median difference
      between THIN and validated admission dates was +0.5 days, and the absolute mean
      difference was +3.1 days. In 16 of 52 admitted patients, the THIN admission date
      was the actual discharge date. CONCLUSIONS: THIN hospitalization codes performed
      well in identifying acute pneumonia hospitalizations and their timing. Admission
      date validity might be better for conditions associated with shorter versus
      longer hospitalizations.

PMID- 22374685
TI  - Clinical characteristics and natural course of recurrent vestibulopathy: a long
      term follow-up study.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the clinical characteristics and the
      natural course of recurrent vestibulopathy (RV). STUDY DESIGN: Retrospective
      study. METHODS: During the period April 2002 to February 2008, we reviewed the
      clinical records of 98 patients diagnosed with RV. All patients were approached
      by telephone and using a questionnaire. The analysis included age, sex
      distribution, natural history, pure-tone audiometry, caloric response, age at
      onset, and the characteristics of vertigo. RESULTS: Median follow-up was 63.1
      months (range, 24-103 months). Patients had a mean age at onset of 39 years and a
      mean duration of 4.2 years. An obvious female predilection was found, and
      unilateral caloric paresis (>= 25%) was seen in 35%. Of the 98 patients, symptoms
      resolved in 82% but were unchanged in 12%. RV developed to Meniere's disease in
      four patients and to migraine in two. No patient with RV developed a central
      nervous system disease or benign paroxysmal positional vertigo during follow-up.
      CONCLUSIONS: The study suggests that in the majority of cases, vertigo
      spontaneously resolves and that the risks of development to Meniere's disease or
      migraine are low.

PMID- 22374686
TI  - Proper cerebellar development requires expression of beta1-integrin in Bergmann
      glia, but not in granule neurons.
AB  - beta1-class integrins play essential roles both in developmental biology as well
      as in cancer. Particularly, a Nestin-driven deletion of beta1-integrin receptors
      results in severe abnormalities of brain development including a laminar
      disorganization of cerebellar granule neurons. However, since Nestin is expressed
      in all kinds of neural precursors, these data do not allow conclusions to be
      drawn about the role of beta1-integrins in distinct neuronal and glial cell
      types. By generating conditional knockout mice using granule cell-specific Math1
      promoter sequences, we show here that the expression of beta1-integrins in
      granule neurons is dispensable for the development of the cerebellum. Also,
      deletion of beta1-integrin from tumors that arise in a mouse model of granule
      cell precursor-derived medulloblastoma did not result in a significant survival
      benefit. Last, expression levels of beta1-integrin in human medulloblastoma
      samples did not predict patient's outcome. However, a beta1-integrin knockout
      using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate
      positioning of Bergmann glia cells in the molecular layer, undirected outgrowth
      of radial glia fibers, and granule cell ectopia. We therefore conclude that beta1
      integrin expression in cerebellar granule neurons is not essential during normal
      development or medulloblastoma formation. In fact, it is the expression of beta1
      integrin in glia that is crucial for the proper development of the cerebellar
      cortex.

PMID- 22374687
TI  - From bygones to perspectives.

PMID- 22374689
TI  - Characterization of the Fe-H bond in a three-coordinate terminal hydride complex
      of iron(I).

PMID- 22374690
TI  - Best practice in substance misuse.
AB  - While substance misuse by adolescents in the UK has declined over the last
      decade, the UK continues to have some of the highest rates of alcohol and drug
      use in Europe. Many young people will try smoking and drinking alcohol during
      their adolescence and a significant minority will misuse alcohol and illicit
      drugs. This behaviour remains a significant cause for concern owing to its
      associated risks to the health and wellbeing of adolescents. Guidance is emerging
      regarding good practice in the assessment and management of adolescent substance
      misuse. Paediatricians may encounter substance-misusing adolescents in a variety
      of clinical settings and can play a valuable role in the screening, management
      and support of this group of young people.

PMID- 22374691
TI  - Loss of bladder smooth muscle caveolae in the aging bladder.
AB  - AIMS: Caveolae are specialized regions of the cell membrane that modulate signal
      transduction and alterations in these structures affect bladder smooth muscle
      (BSM) contraction. Since bladder dysfunctions are common in the elderly, we
      evaluated the effect of aging on the morphology of caveolae and caveolin protein
      expression in BSM. METHODS: Caveolar morphology (number, size, and depth) in BSM
      was determined from electron microscopy images of young (10 weeks), adult (6
      month old), and old (12-month old) rat urinary bladders. Changes in expression
      levels of caveolin proteins with age were investigated by Western blot and
      immunofluorescence microscopy. Caveolin-3 gene expression was determined by real
      time RT-PCR in young and 19-month-old rat bladders. RESULTS: Twelve-month-old
      animals exhibited 50% fewer BSM caveolae compared to young (P < 0.01). The area
      of caveolae was significantly decreased at 6 and 12 months. Despite a decrease in
      the number of BSM caveolae at 12 months, the expression of caveolin-1 and cavin-1
      were unaltered with age. In contrast, caveolin-2 and caveolin-3 protein
      expression and immunoreactivity were reduced in BSM at 6 and 12 months of age.
      Caveolin-3 gene expression was also downregulated at 19 months compared to young
      animals. CONCLUSION: Biological aging significantly decreases BSM caveolae number
      and morphology with associated selective alteration in caveolin protein
      expression. Since caveolae are protected membrane regions that regulate signal
      transduction, age-related alterations in caveolae and caveolin protein expression
      could alter BSM contractility resulting in bladder dysfunctions of the elderly.

PMID- 22374693
TI  - Wet-chemical synthesis of amphiphilic rodlike silica particles and their
      molecular mimetic assembly in selective solvents.

PMID- 22374692
TI  - Development of an electrospray LC-MS/MS method for quantification of Delta(9) 
      tetrahydrocannabinol and its main metabolite in oral fluid.
AB  - A fast and sensitive reference method for quantification of Delta(9) 
      tetrahydrocannabinol (THC) and its main metabolite 11-nor-9-carboxy-Delta(9) 
      tetrahydrocannabinol (THCCOOH) in oral fluid is described in this study. Samples
      were collected using an oral specimen collection device, followed by solid-phase
      extraction and liquid chromatography-tandem mass spectrometry analysis.
      Chromatographic separation of the analytes was achieved by gradient elution on a
      reversed-phase column with subsequent detection by electrospray triple quadrupole
      mass spectrometry in positive ionization multiple reaction monitoring mode.
      Quantification was performed by means of deuterated analogues of the analytes as
      internal standards. Total run time of the assay was 12 min. The method allowed
      sensitive quantification of both analytes at a limit of quantification of 0.2
      ng/ml. This sensitivity is essential for analysis of samples collected with the
      Intercept Oral Fluid Collection device (OraSure) and an assay for simultaneous
      quantification of THC and THCCOOH in saliva has not yet been described. The
      calibration curves for THC and THCCOOH were linear in the range between 0.25 and
      8 ng/ml (r(2)  > 0.99). Ion suppression effects from endogenous or exogenous
      interferences were investigated using selected model substances (albumin,
      ascorbic acid, bilirubin, hemoglobin, breath spray, cigarette, chewing gum,
      chewing tobacco, candy, tooth whitening, and Tums antacid). These substances were
      chosen because of the high probability of their presence in the collected
      samples. None of the 11 endogenous model interferences altered the accuracy of
      analysis, demonstrating good robustness of the method with respect to
      interferences in common hygiene products, medicine, tobacco and naturally
      occurring endogenous substances.

PMID- 22374694
TI  - Facilitating the mineralization of oligo(poly(ethylene glycol) fumarate) hydrogel
      by incorporation of hydroxyapatite nanoparticles.
AB  - Exploring strategies to induce the mineralization of hydrogels is an important
      step toward the development of hydrogel-based materials for bone regeneration. In
      the current study, the effect of incorporating hydroxyapatite (HA) nanoparticles
      on the mineralization capacity of an inert poly(ethylene glycol) (PEG)-based
      hydrogel was investigated. HA nanoparticles were either directly loaded into
      oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel or loaded into commonly used
      gelatin microsphere porogens that were subsequently integrated in the OPF matrix.
      Mineralization of composites after immersion of the samples in simulated body
      fluid up to 28 days was assessed. In contrast to the blank OPF hydrogel, the HA
      containing constructs strongly mineralized such that the average rate of calcium
      uptake by the material was enhanced by orders of magnitude. The mineral formed
      was observed to be apatitic and needle shaped. The presented method allows
      modification of inert PEG-based hydrogels into bioactive biomaterials for
      applications in bone regeneration.

PMID- 22374695
TI  - Distinct but phenotypically heterogeneous human cell populations produce rapid
      recovery of platelets and neutrophils after transplantation.
AB  - Delayed recovery of mature blood cells poses a serious, expensive, and often life
      threatening problem for many stem cell transplantation recipients, particularly
      if heavily pretreated and serving as their own donor, or having a CB
      transplantation as the only therapeutic option. Importantly, the different cells
      required to ensure a rapid, as well as a permanent, hematopoietic recovery in
      these patients remain poorly defined. We now show that human CB and mobilized
      peripheral blood (mPB) collections contain cells that produce platelets and
      neutrophils within 3 weeks after being transplanted into sublethally irradiated
      NOD/scid-IL-2Rgammac-null mice. The cells responsible for these 2 outputs are
      similarly distributed between the aldehyde dehydrogenase-positive and -negative
      subsets of lineage marker-negative CB and mPB cells, but their overall
      frequencies vary independently in individual samples. In addition, their total
      numbers can be seen to be much (> 30-fold) lower in a single "average" CB
      transplantation compared with a single "average" mPB transplantation (normalized
      for a similar weight of the recipient), consistent with the published
      differential performance in adult patients of these 2 transplantation products.
      Experimental testing confirmed the clinical relevance of the surrogate
      xenotransplantation assay for quantifying cells with rapid platelet regenerative
      activity, underscoring its potential for future applications.

PMID- 22374696
TI  - The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in
      NPM1 unmutated, AML with a normal karyotype.
AB  - The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of
      patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated
      to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a
      significant independent effect of the quantitative FLT3ITD mRNA level--measured
      as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was
      clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319
      patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression
      model, the quantitative FLT3ITD mRNA level showed an independent prognostic
      impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+
      subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS:
      hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to
      relapse risk stratification and might help to guide postremission therapy in NPM1
      mutated AML.

PMID- 22374697
TI  - Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin
      lymphomas identified through genomic profiling.
AB  - Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B
      cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are
      treated similarly in children and both entities have superior outcomes in
      children compared with adults. Gene expression profiling (GEP) and miRNA
      expression profiling clearly differentiated pediatric DLBCL from BL, forming
      distinct clusters regardless of patient age. However, pathway analysis of GEP
      data identified minor differences between corresponding pediatric and adult
      tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B
      cell subtype was found among pediatric DLBCL. Two cases were molecularly
      classified as primary mediastinal B-cell lymphoma. We observed frequent
      abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5
      of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC
      rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis
      identified abnormalities that are shared between adult and pediatric DLBCL
      (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, 
      19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age.
      Elucidation of the underlying target genes may provide insight into factors that
      modulate outcome and could provide potential novel therapeutic targets with less
      toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.

PMID- 22374699
TI  - Tissue factor and glycoprotein C on herpes simplex virus type 1 are protease
      activated receptor 2 cofactors that enhance infection.
AB  - The coagulation system provides physiologic host defense, but it can also be
      exploited by pathogens for infection. On the HSV1 surface, host-cell-derived
      tissue factor (TF) and virus-encoded glycoprotein C (gC) can stimulate protease
      activated receptor 1 (PAR1)-enhanced infection by triggering thrombin production.
      Using novel engineered HSV1 variants deficient in either TF and/or gC, in the
      present study, we show that activated coagulation factors X (FXa) or VII (FVIIa)
      directly affect HSV1 infection of human umbilical vein endothelial cells in a
      manner that is dependent on viral TF and gC. The combination of FXa and FVIIa
      maximally enhanced infection for TF(+)/gC(+) HSV1 and receptor desensitization
      and Ab inhibition demonstrated that both proteases act on PAR2. Inhibitory TF Abs
      showed that the required TF source was viral. Individually, TF or gC partly
      enhanced the effect of FXa, but not FVIIa, revealing gC as a novel PAR2 cofactor
      for FVIIa. In sharp contrast, thrombin enhanced infection via PAR1 independently
      of viral TF and gC. Thrombin combined with FXa/FVIIa enhanced infection,
      suggesting that PAR1 and PAR2 are independently involved in virus propagation.
      These results show that HSV1 surface cofactors promote cellular PAR2-mediated
      infection, indicating a novel mode by which pathogens exploit the initiation
      phase of the host hemostatic system.

PMID- 22374698
TI  - An acute negative bystander effect of gamma-irradiated recipients on transplanted
      hematopoietic stem cells.
AB  - Ultimate success of hematopoietic stem cell transplantation (HSCT) depends not
      only on donor HSCs themselves but also on the host environment. Total body
      irradiation is a component in various host conditioning regimens for HSCT. It is
      known that ionizing radiation exerts "bystander effects" on nontargeted cells and
      that HSCs transplanted into irradiated recipients undergo proliferative
      exhaustion. However, whether irradiated recipients pose a proliferation
      independent bystander effect on transplanted HSCs is unclear. In this study, we
      found that irradiated mouse recipients significantly impaired the long-term
      repopulating ability of transplanted mouse HSCs shortly (~ 17 hours) after
      exposure to irradiated hosts and before the cells began to divide. There was an
      increase of acute cell death associated with accelerated proliferation of the
      bystander hematopoietic cells. This effect was marked by dramatic down-regulation
      of c-Kit, apparently because of elevated reactive oxygen species. Administration
      of an antioxidant chemical, N-acetylcysteine, or ectopically overexpressing a
      reactive oxygen species scavenging enzyme, catalase, improved the function of
      transplanted HSCs in irradiated hosts. Together, this study provides evidence for
      an acute negative, yet proliferation-independent, bystander effect of irradiated
      recipients on transplanted HSCs, thereby having implications for HSCT in both
      experimental and clinical scenarios in which total body irradiation is involved.

PMID- 22374700
TI  - Mcl-1 and Bcl-x(L) coordinately regulate megakaryocyte survival.
AB  - Mature megakaryocytes depend on the function of Bcl-x(L), a member of the Bcl-2
      family of prosurvival proteins, to proceed safely through the process of platelet
      shedding. Despite this, loss of Bcl-x(L) does not prevent the growth and
      maturation of megakaryocytes, suggesting redundancy with other prosurvival
      proteins. We therefore generated mice with a megakaryocyte-specific deletion of
      Mcl-1, which is known to be expressed in megakaryocytes. Megakaryopoiesis,
      platelet production, and platelet lifespan were unperturbed in Mcl
      1(Pf4Delta/Pf4Delta) animals. However, treatment with ABT-737, a BH3 mimetic
      compound that inhibits the prosurvival proteins Bcl-2, Bcl-x(L), and Bcl-w
      resulted in the complete ablation of megakaryocytes and platelets. Genetic
      deletion of both Mcl-1 and Bcl-x(L) in megakaryocytes resulted in preweaning
      lethality. Megakaryopoiesis in Bcl-x(Pf4Delta/Pf4Delta) Mcl-1(Pf4Delta/Pf4Delta)
      embryos was severely compromised, and these animals exhibited ectopic bleeding.
      Our studies indicate that the combination of Bcl-x(L) and Mcl-1 is essential for
      the viability of the megakaryocyte lineage.

PMID- 22374702
TI  - Metabolism and excretion studies of oral administered naringin, a putative
      antitussive, in rats and dogs.
AB  - Naringin, a major active flavonone glycoside from a traditional Chinese medicine
      Huajuhong, has been demonstrated to have activities such as peripheral
      antitussive, mucoregulator and anti-inflammatory. The purpose of this study was
      to elucidate the metabolism and mass balance of orally administered naringin in
      rats and dogs. After oral administration of naringin to rats and dogs at doses of
      42 mg/kg and 12.4 mg/kg, respectively, metabolites in excreta were identified
      using a LC-Q-TOF system. The major metabolites including naringin, total
      naringenin (including free naringenin and its conjugates) and 4
      hydroxyphenylpropionic acid in excreta were quantified by a LC-MS/MS system.
      Twenty-two metabolites were identified in dogs and 17 metabolites were detected
      in rats. The observed routes of naringin metabolism were hydroxylation,
      methylation, acetylation, hydrogenation, deglycosylation, dehydrogenation,
      glucuronidation, sulfation, glucosylation, ring-fission, oxidation, glycine
      conjugation and dehydroxylation. On the basis of these identified metabolites, a
      comprehensive metabolic pathway of naringin was proposed. About 21% of
      administered naringin was recovered in rat excreta in the form of naringin, total
      naringenin and 4-hydroxyphenylpropionic acid, and about 60% was recovered in dog
      excreta. The levels of 4-hydroxyphenylpropionic acid in excreta were higher than
      those of naringin and total naringenin, and the quantified metabolites were
      excreted more through feces, rather than urine. Most of these metabolites were
      excreted within 36 h post dose. The results of metabolism and excretion studies
      provide an explanation for future pharmacological and toxicological findings and
      are the groundwork for clinical studies.

PMID- 22374701
TI  - Role of minimal residual disease monitoring in acute promyelocytic leukemia
      treated with arsenic trioxide in frontline therapy.
AB  - Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia
      (APL) are available only in the context of conventional all-trans retinoic acid
      plus chemotherapy regimens. It is recognized that the kinetics of leukemia
      clearance is different with the use of arsenic trioxide (ATO) in the treatment of
      APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring
      study on patients with APL treated with a single agent ATO regimen. A total of
      151 patients were enrolled in this study. A positive RT-PCR reading at the end of
      induction therapy was significantly associated on a multivariate analysis with an
      increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk
      patients who were RT-PCR negative at the end of induction relapsed. The majority
      of the relapses (91%) happened within 3 years of completion of treatment. After
      achievement of molecular remission, the current MRD monitoring strategy was able
      to predict relapse in 60% of cases with an overall sensitivity and specificity of
      60% and 93.2%, respectively. High-risk group patients and those that remain RT
      PCR positive at the end of induction are likely to benefit from serial MRD
      monitoring by RT-PCR for a period of 3 years from completion of therapy.

PMID- 22374703
TI  - Impact of crooked nose rhinoplasty on observer perceptions of attractiveness.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the impact of a crooked nose on observer
      perceptions of facial asymmetry and attractiveness and the ability of rhinoplasty
      to minimize it. We hypothesized that the presence of a crooked nose would
      penalize symmetry and attractiveness ratings as compared to normal faces. We
      further hypothesized that straightening rhinoplasty would restore symmetry and
      improve attractiveness. STUDY DESIGN: Randomized controlled experiment. METHODS:
      A group of 39 naive observers viewed pictures of patients with crooked noses
      before and after straightening rhinoplasty, and normal patients. Observers rated
      the overall asymmetry and attractiveness, and the asymmetry of facial subunits
      using a survey with a rating scale of 1 to 10 for each category. RESULTS: For
      asymmetry, patient group (preoperative, postoperative, normal) was statistically
      significant by multivariate analysis of the variance. Post-analysis of variance
      showed significant differences in asymmetry scores for overall, nose subunit, and
      mouth subunit. Pairwise testing then showed significantly different overall
      asymmetry scores between normal and preoperative (P < .001), and preoperative and
      postoperative (P < .001), but not between normal and postoperative (P = .215)
      groups. Mixed linear regression analysis showed that decreasing nasal asymmetry
      by 1 point increases attractiveness by 0.18 points or 0.082 attractiveness
      standard deviations (P < .001). CONCLUSIONS: Faces with crooked noses were rated
      less symmetrical overall and less symmetrical at the nose and mouth subunits as
      compared to normal and postoperative faces. Straightening rhinoplasty diminished
      overall facial asymmetry and subunit asymmetry scores. Decreasing nasal asymmetry
      led to significant improvements in facial attractiveness. These data provide
      objective evidence supporting the idea that a straightening rhinoplasty can
      improve attractiveness.

PMID- 22374704
TI  - Preparation and photophysical and photoelectrochemical properties of a covalently
      fixed porphyrin-chemically converted graphene composite.
AB  - Chemically converted graphene (CCG) covalently linked with porphyrins has been
      prepared by a Suzuki coupling reaction between iodophenyl-functionalized CCG and
      porphyrin boronic ester. The covalently linked CCG-porphyrin composite was
      designed to possess a short, rigid phenylene spacer between the porphyrin and the
      CCG. The composite material formed stable dispersions in DMF and the structure
      was characterized by spectroscopic, thermal, and microscopic measurements. In
      steady-state photoluminescence spectra, the emission from the porphyrin linked to
      the CCG was quenched strongly relative to that of the porphyrin reference.
      Fluorescence lifetime and femtosecond transient absorption measurements of the
      porphyrin-linked CCG revealed a short-lived porphyrin singlet excited state (38
      ps) without yielding the porphyrin radical cation, thereby substantiating the
      occurrence of energy transfer from the porphyrin excited state to the CCG and
      subsequent rapid decay of the CCG excited state to the ground state.
      Consistently, the photocurrent action spectrum of a photoelectrochemical device
      with a SnO(2) electrode coated with the porphyrin-linked CCG exhibited no
      photocurrent response from the porphyrin absorption. The results obtained here
      provide deep insight into the interaction between graphenes and pi-conjugated
      systems in the excited and ground states.

PMID- 22374705
TI  - Palladium-catalyzed aromatic azidocarbonylation.

PMID- 22374706
TI  - Contrast enhanced CT versus integrated PET-CT in pre-operative nodal staging of
      non-small cell lung cancer.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate the
      effectiveness of integrated positron emission tomography-computed tomography (PET
      CT) in comparison with contrast enhanced CT (CE-CT) in pre-operative staging of
      non-small cell lung cancer (NSCLC) by using surgical and pathological findings as
      the reference standard. MATERIALS AND METHODS: From August 2008 to August 2009,
      57 consecutive patients (50 males and 7 females; mean age, 59 years; range, 38-79
      years) with NSCLC underwent conventional pre-operative lung cancer staging using
      clinical data and CE-CT of the chest, and integrated whole-body fluorine-18
      fluorodeoxyglucose PET-CT studies. Histopathological results served as the
      reference standard. RESULTS: Forty-eight of the 57 patients (84%) had no lymph
      node involvement (N0), five (9%) were found to have N1 disease, and four (7%) had
      N2 disease. There was a significant difference between CE-CT and PET-CT for nodal
      staging of N0 disease (P < 0.05). Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of hilar and mediastinal lymph
      node staging were 56%, 73%, 28%, 90%, and 70%, with CE-CT, respectively; and 78%,
      92%, 64%, 96%, and 89% with PET-CT, respectively. CONCLUSION: Integrated PET-CT
      is more accurate than CE-CT for lymph node staging in NSCLC.

PMID- 22374707
TI  - Drug-induced Stevens-Johnson syndrome: case series from tertiary care centre in
      Gujarat.
AB  - PURPOSE: The aims of the present article were to study clinical features and to
      analyse them in different drug class associated with Stevens-Johnson syndrome
      (SJS) in a tertiary care hospital in Gujarat, India. MATERIALS AND METHODS: A
      prospective hospital-based study was carried out over a period of 3 years (June
      2007 to September 2009) at Sheth Vadilal Hospital, Ahmedabad, India. The
      diagnosis of SJS was made mainly on the basis of the clinical findings, which
      included extensive erythema multiforme, purpuric lesions with bullae and
      detachment of skin involving at least two mucous membranes. Further, in each
      patient suspected with SJS, various laboratory tests such as complete blood
      count, liver function tests, metabolic panel, chest X-ray and other serological
      test were carried out. SJS was confirmed on the basis of most widely accepted
      Bastuji-Garin definition. Causality assessment was performed using the Naranjo
      scale. Only 'probable' and 'definite' reactions were included. RESULTS:
      Antibacterials for systemic use, anti-inflammatory and antirheumatic products and
      antiepileptics were the drug classes most commonly associated (8 of 29 cases,
      each) with SJS. Individually, ibuprofen was involved in the highest number of
      cases (five cases, 17.2%), followed by carbamazepine (four cases, 13.8%) . The
      mean duration of developing SJS symptoms was 15.9 days (SD = 8.7 days) and
      improvement after treatment was 14.2 days (SD = 4.6 days). The duration of
      appearing SJS symptoms varied significantly between different classes of drugs (p
      < 0.001). The appearance of SJS symptom started within 10 days for anti
      inflammatory and antibacterial compared with 24 days of antiepileptic agents. All
      the patients with antiepileptic agent-induced SJS had 7% to 9% of detached body
      surface area. In two patients, SJS progressed to toxic epidermal necrolysis and
      of which one led to death and the other developed long-term complication of
      conjunctival xerosis. A total of six patients developed long-term complications:
      four patients had conjunctival synechia, one patient had conjunctival xerosis and
      one patient had urethral stricture. CONCLUSION: More than 80% of the SJS events
      were induced by antibacterial, anti-inflammatory and antiepileptic agents with
      same frequency. The duration of the appearance of SJS symptoms significantly
      varied between different drug classes and started within 10 days for anti
      inflammatory and antibacterial compared with 24 days of antiepileptic agents.

PMID- 22374708
TI  - Examining the prevalence, role and impact of evidence regarding Antisocial
      Personality, sociopathy and psychopathy in capital cases: a survey of defense
      team members.
AB  - Although anecdotal case accounts suggest that evidence concerning Antisocial
      Personality Disorder (APD), sociopathy and psychopathy is frequently introduced
      by the prosecution in capital murder trials, to date there has been no systematic
      research to determine the actual prevalence, role, or perceived impact of such
      evidence in these cases. Survey data collected from attendees at a national
      capital mitigation conference (n=41) indicated that prosecution evidence
      concerning APD was quite prevalent, with "sociopath" and "psychopath" labels
      being introduced less frequently. Evidence concerning these disorders, which were
      assessed primarily via DSM criteria and self-report personality inventories, was
      most often introduced by the prosecution in the sentencing phase to address a
      defendant's ostensible risk of future dangerousness and/or to rebut mitigating
      evidence-although it was also introduced frequently in the guilt/innocence phase
      of these trials to rebut mental health evidence offered by the defense. Survey
      respondents believed that evidence concerning APD, sociopathy, and psychopathy
      had a considerable impact on trial outcomes. Also, although defense objections
      were common, such evidence was rarely ruled to be inadmissible in these cases.

PMID- 22374709
TI  - Isolation and characterization of living primary astroglial cells using the new
      GLAST-specific monoclonal antibody ACSA-1.
AB  - Astrocytes show large morphological and functional heterogeneity and are involved
      in many aspects of neural function. Progress in defining astrocyte subpopulations
      has been hampered by the lack of a suitable antibody for their direct detection
      and isolation. Here, we describe a new monoclonal antibody, ACSA-1, which was
      generated by immunization of GLAST1 knockout mice. The antibody specifically
      detects an extracellular epitope of the astrocyte-specific L-glutamate/L
      aspartate transporter GLAST (EAAT1, Slc1a3). As shown by immunohistochemistry,
      immunocytochemistry, and flow cytometry, ACSA-1 was cross-reactive for mouse,
      human, and rat. It labeled virtually all astrocytes positive for GFAP, GS, BLBP,
      RC2, and Nestin, including protoplastic, fibrous, and reactive astrocytes as well
      as Bergmann glia, Muller glia, and radial glia. Oligodendrocytes, microglia,
      neurons, and neuronal progenitors were negative for ACSA-1. Using an
      immunomagnetic approach, we established a method for the isolation of GLAST
      positive cells with high purity. Binding of the antibody to GLAST and subsequent
      sorting of GLAST-positive cells neither interfered with cellular glutamate
      transport nor compromised astrocyte viability in vitro. The ACSA-1 antibody is
      not only a valuable tool to identify and track astrocytes by immunostaining, but
      also provides the possibility of separation and further analysis of pure
      astrocytes.

PMID- 22374710
TI  - Recent instrumental progress in mass spectrometry: advancing resolution,
      accuracy, and speed of drug detection.
AB  - Fast and unequivocal drug detection is of considerable importance in numerous
      fields of analytical chemistry, and today mass spectrometry-based approaches are
      often the method of choice due to their sensitive and specific nature. Mass
      spectrometry is in constant flux with innovations and thus supports the
      development of new, complementary assays for rapid determination of drugs and
      toxins as well as their metabolic products in clinical, forensic, and doping
      control laboratories. Examples of such innovations that have greatly aided the
      worldwide bioanalytical efforts are the modern improvements in ion trap, for
      example, Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer-
      Orbitrap, and time-of-flight (TOF) mass analyzers when coupled with sensitive
      ionization techniques such as electrospray ionization. In this perspective, the
      utility of state-of-the-art mass spectrometers and recent instrumental
      developments such as new and/or improved hybrid analyzers are discussed and
      selected applications presented.

PMID- 22374711
TI  - Foldamers: they're not just for biomedical applications anymore.

PMID- 22374712
TI  - Preparation and in vitro characterization of electrospun PVA scaffolds coated
      with bioactive glass for bone regeneration.
AB  - An important objective in bone tissue engineering is to fabricate biomimetic
      three-dimensional scaffolds that stimulate mineralization for rapid regeneration
      of bone. In this work, scaffolds of electrospun poly(vinyl alcohol) (PVA) fibers
      (diameter = 286 +/- 14 nm) were coated with a sol-gel derived bioactive glass
      (BG) and evaluated in vitro for potential applications in bone repair. Structural
      and chemical analyses showed that the BG coating was homogeneously deposited on
      the PVA fibers. In vitro cell culture studies showed that the BG-coated PVA
      scaffold had a greater capacity to support proliferation of osteogenic MC3T3-E1
      cells, alkaline phosphatase activity, and mineralization than the uncoated PVA
      scaffold. The BG coating improved the tensile strength of the PVA scaffold from
      18 +/- 2 MPa to 21 +/- 2 MPa, but reduced the elongation to failure from 94 +/-
      4% to 64 +/- 5%. However, immersion of the BG-coated PVA scaffolds in a simulated
      body fluid for 5 days resulted in an increase in the tensile strength (24 +/- 2
      MPa) and elongation to failure (159 +/- 4%). Together, the results show that
      these BG-coated PVA scaffolds could be considered as candidate materials for bone
      tissue engineering applications.

PMID- 22374713
TI  - Oestrogen attenuates tumour progression in hepatocellular carcinoma.
AB  - The precise mechanisms underlying gender disparity in hepatocellular carcinoma
      (HCC) progression and prognosis are not understood. We demonstrate that oestrogen
      attenuates HCC progression in vitro and in vivo, and this may contribute to the
      gender differences in HCC behaviour. To investigate the role of oestrogen in HCC
      progression, we developed an orthotopic homograft tumour model by liver
      implantation of H22 cells. In combination with male castration, female
      ovariectomy, and oestrogen treatment, we tested the hypothesis that oestrogen
      contributes to gender disparity in this model. Pathological analyses were
      performed to examine the changes in biological behaviour of liver cancer cells,
      and two cell lines were used to investigate possible molecular mechanisms of the
      suppressive effect of oestrogen. Our data showed that oestrogen modulates HCC
      malignancy in vivo by reducing tumour cell invasion, arresting cell cycle
      progression, and promoting apoptosis, characterized by decreased expression of
      MMP-2, MMP-9, PCNA, cyclin A, cyclin D1, and Bcl-2, and increased expression in
      cleaved caspase 3. Through in vitro assays, we further confirmed the changes in
      expression levels of these related proteins, gained insights into the molecular
      cascades of oestrogen-induced HCC suppression, and indicated the oestrogen
      receptor alpha-mediated inhibition of NF-kappaB binding activity as a pivotal
      event in this process. This study represents a novel description of the
      mechanisms regarding the suppressive effects of oestrogen on HCC, adding a new
      understanding to the gender disparity in HCC progression. Copyright (c) 2012
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 22374714
TI  - A case study on the in silico absorption simulations of levothyroxine sodium
      immediate-release tablets.
AB  - The aim of this case study was to develop a drug-specific absorption model for
      levothyroxine (LT4) using mechanistic gastrointestinal simulation technology
      (GIST) implemented in the GastroPlusTM software package. The required input
      parameters were determined experimentally, in silico predicted and/or taken from
      the literature. The simulated plasma profile was similar and in a good agreement
      with the data observed in the in vivo bioequivalence study, indicating that the
      GIST model gave an accurate prediction of LT4 oral absorption. Additionally,
      plasma concentration-time profiles were simulated based on a set of experimental
      and virtual in vitro dissolution data in order to estimate the influence of
      different in vitro drug dissolution kinetics on the simulated plasma profiles and
      to identify biorelevant dissolution specification for LT4 immediate-release (IR)
      tablets. A set of experimental and virtual in vitro data was also used for
      correlation purposes. In vitro-in vivo correlation model based on the convolution
      approach was applied in order to assess the relationship between the in vitro and
      in vivo data. The obtained results suggest that dissolution specification of more
      than 85% LT4 dissolved in 60 min might be considered as biorelevant dissolution
      specification criteria for LT4 IR tablets.

PMID- 22374715
TI  - Palladium(0)-catalyzed synthesis of cross-conjugated polymers: transformation
      into linear-conjugated polymers through the Diels-Alder reaction.

PMID- 22374716
TI  - Theoretical study on the mechanism of Ni-catalyzed alkyl-alkyl Suzuki cross
      coupling.
AB  - Ni-catalyzed cross-coupling of unactivated secondary alkyl halides with
      alkylboranes provides an efficient way to construct alkyl-alkyl bonds. The
      mechanism of this reaction with the Ni/L1 (L1=trans-N,N'-dimethyl-1,2
      cyclohexanediamine) system was examined for the first time by using theoretical
      calculations. The feasible mechanism was found to involve a Ni(I)-Ni(III)
      catalytic cycle with three main steps: transmetalation of [Ni(I)(L1)X] (X=Cl, Br)
      with 9-borabicyclo[3.3.1]nonane (9-BBN)R(1) to produce [Ni(I)(L1)(R(1))],
      oxidative addition of R(2) X with [Ni(I)(L1)(R(1))] to produce
      [Ni(III)(L1)(R(1))(R(2))X] through a radical pathway, and C-C reductive
      elimination to generate the product and [Ni(I)(L1)X]. The transmetalation step is
      rate-determining for both primary and secondary alkyl bromides. KOiBu decreases
      the activation barrier of the transmetalation step by forming a potassium alkyl
      boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because
      the activation barrier of reductive elimination is too high (+34.7 kcal mol(-1)).
      On the other hand, the cross-coupling of alkyl chlorides can be catalyzed by
      Ni/L2 (L2=trans-N,N'-dimethyl-1,2-diphenylethane-1,2-diamine) because the
      activation barrier of transmetalation with L2 is lower than that with L1.
      Importantly, the Ni(0)-Ni(II) catalytic cycle is not favored in the present
      systems because reductive elimination from both singlet and triplet
      [Ni(II)(L1)(R(1))(R(2))] is very difficult.

PMID- 22374717
TI  - Clarifying the importance of CYP2C19 and PON1 in the mechanism of clopidogrel
      bioactivation and in vivo antiplatelet response.
AB  - AIMS: It is thought that clopidogrel bioactivation and antiplatelet response are
      related to cytochrome P450 2C19 (CYP2C19). However, a recent study challenged
      this notion by proposing CYP2C19 as wholly irrelevant, while identifying
      paraoxonase-1 (PON1) and its Q192R polymorphism as the major driver of
      clopidogrel bioactivation and efficacy. The aim of this study was to
      systematically elucidate the mechanism and relative contribution of PON1 in
      comparison to CYP2C19 to clopidogrel bioactivation and antiplatelet response.
      METHODS AND RESULTS: First, the influence of CYP2C19 and PON1 polymorphisms and
      plasma paraoxonase activity on clopidogrel active metabolite (H4) levels and
      antiplatelet response was assessed in a cohort of healthy subjects (n = 21) after
      administration of a single 75 mg dose of clopidogrel. There was a remarkably good
      correlation between H4 AUC (0-8 h) and antiplatelet response (r2 = 0.78).
      Furthermore, CYP2C19 but not PON1 genotype was predictive of H4 levels and
      antiplatelet response. There was no correlation between plasma paraoxonase
      activity and H4 levels. Secondly, metabolic profiling of clopidogrel in vitro
      confirmed the role of CYP2C19 in bioactivating clopidogrel to H4. However,
      heterologous expression of PON1 in cell-based systems revealed that PON1 cannot
      generate H4, but mediates the formation of another thiol metabolite, termed Endo.
      Importantly, Endo plasma levels in humans are nearly 20-fold lower than H4 and
      was not associated with any antiplatelet response. CONCLUSION: Our results
      demonstrate that PON1 does not mediate clopidogrel active metabolite formation or
      antiplatelet action, while CYP2C19 activity and genotype remains a predictor of
      clopidogrel pharmacokinetics and antiplatelet response.

PMID- 22374718
TI  - Lost contact with vessel wall, signed contract with stent thrombosis?

PMID- 22374719
TI  - A toolbox of lectins for translating the sugar code: the galectin network in
      phylogenesis and tumors.
AB  - Lectin histochemistry has revealed cell-type-selective glycosylation. It is under
      dynamic and spatially controlled regulation. Since their chemical properties
      allow carbohydrates to reach unsurpassed structural diversity in oligomers, they
      are ideal for high density information coding. Consequently, the concept of the
      sugar code assigns a functional dimension to the glycans of cellular
      glycoconjugates. Indeed, multifarious cell processes depend on specific
      recognition of glycans by their receptors (lectins), which translate the sugar
      encoded information into effects. Duplication of ancestral genes and the
      following divergence of sequences account for the evolutionary dynamics in lectin
      families. Differences in gene number can even appear among closely related
      species. The adhesion/growth-regulatory galectins are selected as an instructive
      example to trace the phylogenetic diversification in several animals, most of
      them popular models in developmental and tumor biology. Chicken galectins are
      identified as a low-level-complexity set, thus singled out for further detailed
      analysis. The various operative means for establishing protein diversity among
      the chicken galectins are delineated, and individual characteristics in
      expression profiles discerned. To apply this galectin-fingerprinting approach in
      histopathology has potential for refining differential diagnosis and for
      obtaining prognostic assessments. On the grounds of in vitro work with tumor
      cells a strategically orchestrated co-regulation of galectin expression with
      presentation of cognate glycans is detected. This coordination epitomizes the far
      reaching physiological significance of sugar coding.

PMID- 22374720
TI  - Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and
      diclofenac sodium association.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the purpose of
      anti-inflammation, antipyretic, and analgesia. For this aim, they are used for
      the alleviation of pain, fever, and inflammation associated with rheumatoid
      arthritis, sports injuries, and temporary pain. However, treatment with NSAIDs
      may be accompanied by adverse effects such as gastrointestinal damage and
      platelet dysfunction. As with the other NSAIDs, diclofenac sodium (sodium-(o
      ((2,6-dichlorophenyl)-amino)-phenyl)-acetate) (DS), an NSAID, has potent anti
      inflammatory, analgesic, and antipyretic effects. However, treatment with DS may
      cause some adverse cerebral and cerebellar effects such as convulsions,
      disorientation, hallucination, and loss of consciousness. Melatonin (MLT) is a
      free-radical scavenger and possesses antioxidant properties. It has been reported
      to easily cross the blood-brain barrier, and is found in high concentrations in
      the brain after exogenous administration. It is also a neuroprotector in a wide
      range of conditions affecting the central nervous system CNS due to its free
      radical scavenging activities and lipophilic-hydrophilic properties.
      Neuroprotective actions of MLT have been discovered in both in vitro and in vivo,
      and are a powerful scavenger of oxygen and nitrogen free radicals. Thus, MLT can
      protect the cell membrane, organelles, and core against free-radical damage.
      Therefore, it has been postulated that exogenous MLT acts as a neuroprotector
      contrary to DS neurotoxicity. In this review, we aimed to discuss the possible
      neuroprotective effects of MLT on DS toxicity.

PMID- 22374721
TI  - Post-translational modifications of p53 tumor suppressor: determinants of its
      functional targets.
AB  - Tumor suppressor p53 functions as a "guardian of the genome" to prevent cells
      from transformation. p53 is constitutively ubiquitinated and degradated in
      unstressed conditions, thereby suppressing the expression. However, cellular
      stimuli enable p53 to escape from the negative regulation, and then stably
      expressed p53 transactivates its target genes to induce cell cycle arrest, DNA
      repair, or apoptosis. Promoter preference of target genes is determined by
      modification status of p53. Because p53 has two critical roles in the decision of
      cell fate, stopping cell cycle to repair damaged DNA or induction of apoptotic
      cell death in response to DNA damage, elucidation of switching mechanisms on p53
      functions is of particular importance. Here we review recent evidence how several
      post-translational modifications of p53 including methylation, phosphorylation,
      acetylation, and ubiquitination, affect the functions of p53 in response to
      cellular stress.

PMID- 22374722
TI  - Germ cell sex and cell cycle.
AB  - Germ cells are the only cells in the body capable of transferring an individual's
      genetic and epigenetic information to the next generation. However, the
      developmental processes that provide the foundation for male and female germ line
      development and later gamete production are complex and poorly understood. In
      mice the primordial germ cells enter the bipotential gonad at E10.5 and, in
      response to the testicular or ovarian micro-environment, commit to
      spermatogenesis or oogenesis. This paper reviews progress in understanding the
      molecular processes underlying the early stages of male and female germ line
      development.

PMID- 22374723
TI  - Histological and immunohistochemical assessment of liver biopsies in morbidly
      obese patients.
AB  - AIMS: To study liver lesions in morbidly obese patients who underwent liver
      biopsy at the time of bariatric surgery to define histological lesions,
      especially inflammatory infiltrate, diagnostic categories and the possible
      influence of gender in this respect. METHODS AND RESULTS: 110 biopsies (36 males
      M- and 76 females -F-) were evaluated and categorised, according to the NAS
      (NAFLD -non alcoholic fatty liver disease- Activity Score) system and other
      criteria, as non-NAFLD (15.5%, F predominance), non-alcoholic steatohepatitis
      (NASH) (16.5%, M predominance), non-alcoholic hepatosteatosis (NAHS) (21%, F
      predominance) and, the most numerous group, NASH-borderline (NASH-BORD) (47%),
      with three subgroups, characterised by centrozonal lesions, portal area
      preferential involvement or affecting both areas. The predominant form of
      hepatocytesteatosis was mixed with a multivesicular component that was present in
      most cases with fibroinflammatory portal involvement. Nuclear glycogenosomes were
      found in greater number of biopsies in patients in the third and sixth decades.
      Portal inflammation was present in a large number of cases (M predominance); the
      application of immunohistochemical techniques (myeloperoxidase and CD68
      antibodies) to evaluate lobular inflammation revealed "surgical hepatitis" in one
      third of the cases, and the presence of microgranulomas (CD68+) (M predominance),
      which were more abundant with increasing lesion severity. CONCLUSIONS: Portal
      inflammation and multivesicular hepatocytesteatosis are highly prevalent in
      morbidly obese patients. This study identifies a new subtype of NASH-BORD
      characterized by centrizonal and porto-periportal area involvement and the
      existence of liver biopsies without steatosis. CD68+ microgranulomas constitute
      an unequivocal marker of lobular inflammation in surgical biopsies and of lesion
      severity, which is gender-related.

PMID- 22374724
TI  - Desmosomes in verrucous carcinoma of the head and neck.
AB  - Verrucous carcinoma (VC) is a variant of squamous cell carcinoma (SCC),
      characterised by its inability to metastasize. In contrast, hybrid carcinomas,
      composed of VC and foci of conventional SCC, harbour a metastatic potential.
      Correct pathohistological diagnosis is therefore crucial for the choice of
      treatment. There is mounting evidence that desmosomes are involved in several
      aspects of carcinogenesis. Previous studies have shown an altered expression of
      desmosomal components in conventional SCC, which was associated with tumour
      behaviour, but no data have been found on desmosomes in VC.   We therefore
      analysed the expression of desmosomal components in biopsy samples of 21 cases of
      VC and 5 cases of hybrid carcinoma of the head and neck in comparison to 23 cases
      of conventional SCC and 47 samples of normal squamous epithelium of similar
      localisation, using immunohistochemistry and real-time reverse-transcription
      polymerase chain reaction.   We found that the expression patterns of desmosomal
      components in VC were fairly similar to those in normal epithelium but differed
      significantly from those in conventional SCC. Immunohistochemical reactions
      against desmosomal components disclosed the foci of SCC in hybrid carcinomas.  
      In conclusion, we believe that expression patterns of desmosomal components in VC
      are consistent with its less aggressive behaviour. Differential expression of
      desmosomal components between VC and SCC makes some desmosomal components
      potentially useful in the diagnostics of VC, especially for the detection of
      hybrid carcinoma.

PMID- 22374725
TI  - Nuclear localization of GLI1 and elevated expression of FOXC2 in breast cancer is
      associated with the basal-like phenotype.
AB  - Aberrant sonic hedgehog (SHH)/glioma-associated oncogene (GLI) signaling has been
      shown in the development of many tumors. The aims of the present study are to
      determine the expression of two SHH signaling molecules, the glioma-associated
      oncogene homolog 1 (GLI1) and forkhead box C2 (FOXC2), in invasive breast cancers
      (IBC), to evaluate their association with clinicopathological parameters, and to
      determine their prognostic significance in breast cancer patients. Expression of
      GLI1 and FOXC2 were assessed by immunohistochemical analysis of a tissue
      microarray containing 262 unselected IBC cases. A statistical analysis was
      performed to assess the correlation of GLI1 and FOXC2 expression with the
      patients' clinicopathological parameters, postoperative survival rate, and
      molecular subtypes. Immunoreactivity of GLI1 and FOXC2 was observed in 84% and
      75% of all breast cancer tissues, respectively. There was a significant
      correlation between nuclear FOXC2 and GLI1 expressions in these breast cancers,
      which was associated with estrogen receptor (ER) negativity. Furthermore, there
      was a significant association between nuclear expression of GLI1 and FOXC2 and a
      basal-like breast cancer phenotype. Patients with nuclear GLI1 or FOXC2
      expressing tumors had a significantly shorter survival time than those without
      nuclear FOXC2 or GLI1 expression. Multivariate analysis showed that nuclear GLI1
      or FOXC2 expression was an independent factor for predicting the prognosis of
      basal-like breast cancer. In conclusion, there was a significant correlation
      between expression of nuclear GLI1 or FOXC2 and human breast cancer. More
      specifically, elevated levels of these proteins were associated with the basal
      like breast cancer phenotype and with a poor rate of disease-free survival. These
      data suggest that GLI1 and FOXC2 are involved in tumorigenesis and that they may
      be useful as diagnostic and therapeutic targets for human basal-like breast
      cancers. Additional studies are warranted to better understand the biological
      significance of GLI1 and FOXC2, to further refine statistics related to patient
      prognosis, and to optimize treatment of patients with basal-like breast cancer.

PMID- 22374726
TI  - Application of poly-L-lactide screws in flat foot surgery: histological and
      radiological aspects of bio-absorption of degradable devices.
AB  - The flat foot in childhood is a condition frequently observed in orthopedic
      practice but it is still debated when and in which patients surgical corrective
      treatment is appropriate; recently, the application of poly-L-lactic-acid (PLLA)
      screws was proposed. The present study investigates a group of 33 patients
      treated with PLLA expansion endorthesis in order to evaluate the deformity
      correction. Clinical and radiological outcomes in patients were correlated with:
      a) morphological characterization of screws both before and after being removed
      from patients, when necessary; b) histological and bio-molecular evaluation of
      degradation processes of the implants, focusing attention on the correlation
      between the cellular cohort involved in inflammatory reaction and the bio
      absorption degree of PLLA screws. Deformity correction was mostly achieved, with
      minimal need of screw removal; the results obtained clearly show the occurrence
      of chronic rather than acute inflammation in removed screw specimens.  At the
      histological level, after biomaterial implantation, the sequence of events
      occurring in the surrounding tissues ultimately ends in the formation of foreign
      body giant cells (FBGCs) at the tissue/material interface; but the mechanisms
      which influence the fate of screw implants, i.e. the resolution of acute
      inflammation rather than the progression towards chronic inflammation, are of
      crucial importance for biodegradable materials like "polylactic acid". In fact,
      the FBGC response ensures a long-term mechanism which eliminates the foreign
      material from the body, but at the same time the implications of prolonged FBGC
      responses, which generate negative side effects, could significantly impede the
      healing progress.

PMID- 22374727
TI  - Topotecan hydrochloride effects on retinal vessels in newborn rats.
AB  - A physiological system, i.e. rodent retina during vessel formation and
      hierarchical organization, was utilised for assaying antiangiogenic properties of
      Topotecan, a topoisomerase I inhibitor, capable of inhibiting tumoral growth in
      animal models of retinoblastoma. In particular we analysed possible differences
      in effectiveness and side effects among different drug dosages and ways of
      administration. In the present research only qualitative analyses were
      undertaken. After preliminary experiments, in which suckling animals
      subcutaneously treated with Topotecan dosages comprised between 9 and 3 mg/kg
      underwent high lethality and extremely severe systemic damages, 7 day-old rats
      were subcutaneously, intravenously or peribulbary injected with a single dose of
      1 mg/kg; retinal vessels were visualized in retinal fluorangio-graphies taken 1
      and 2 weeks after treatment. The most important and frequent alterations were
      found to affect radial vessels, which showed non-perfused and/or regionally
      mislocated segments, together with abnormal branching and enlargements in retinal
      periphery; persistence of capillary-free periarteriolar regions, non-vascularised
      regions and spots of extravascular FITC were also detected. Despite the high
      individual variability the alterations were substantially similar among the
      different ways of drug administration, while they appeared milder in 21 day-old
      rats, with respect to younger ones. The extensive vascular remodelling found
      after Topotecan administration, besides demonstrating the antiangiogenic
      properties of this chemioterapic drug, confirms the rodent retina as a highly
      valuable model system for studying angiogenesis modulation.

PMID- 22374728
TI  - Expression of the carbohydrate tumour marker Sialyl Lewis A, Sialyl Lewis X,
      Lewis Y and Thomsen-Friedenreich antigen in normal squamous epithelium of the
      uterine cervix, cervical dysplasia and cervical cancer.
AB  - The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y
      (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion
      between tumor cells and endothelium. They are used as serum markers in diagnosis
      and treatment in a broad spectrum of human carcinomas, but their expression
      profile and role in the development of cervical cancer remains unclear. The aim
      of this study was to investigate the expression of SLeX, SLeA, LeY and TF in
      normal cervical squamous epithelium, cervical dysplasia and cervical cancer.
      Slides of paraffin-embedded tissue were fixed and incubated with monoclonal
      antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was
      evaluated by using a semi-quantitative score (IRS Score).  We found a significant
      difference of SLeA expression in invasive cervical cancer compared to normal
      epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of
      SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036).
      Staining for LeY showed the weakest results of the investigated markers.
      Significant differences were found when normal epithelium was compared to CIN I
      (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF,
      significant differences were found in normal epithelium compared to CIN I
      (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). 
      This is the first study on the expression of SLeA, SLeX, LeY and TF in normal
      cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical
      cancer. Further studies and higher numbers are desirable.

PMID- 22374729
TI  - Immunophenotypical analyses of myofibroblasts in rat excisional wound healing:
      possible transdifferentiation of blood vessel pericytes and perifollicular dermal
      sheath cells into myofibroblasts.
AB  - Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing
      collagen; the derivation and features remain to be investigated.
      Immunophenotypical characteristics of myofibroblasts were analysed in excisional
      rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to
      26. Myofibroblasts were characterized for expressions of intermediate
      cytoskeletons such as vimentin, desmin, and alpha-smooth muscle actin (alpha
      SMA). To pursue the progenitor, immunolabeling analyses were performed using
      stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to
      vimentin and alpha-SMA were first seen on PW day 5, then peaked on PW day 9 in
      granulation tissues, and gradually decreased in remodeling tissues; these
      immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were
      limited to newly-formed blood vessels in wound bed. The single/double
      immunolabelings revealed that pericytes (identified by positive reaction to PDGFR
      beta and negative reaction to endothelial markers) in newly-developing blood
      vessels reacted to vimentin, alpha-SMA, Thy-1 and A3, and occasionally to desmin,
      and that perifollicular dermal sheath cells in the wound periphery showed
      increased expressions for vimentin, Thy-1 and A3. There is considerable
      immunophenotypical similarity between myofibroblasts (expressing vimentin, alpha
      SMA and Thy-1), pericytes (reacting to vimentin, alpha-SMA, Thy-1 and A3) in
      newly-developing blood vessels, and perifollicular dermal sheath cells (reacting
      to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous
      fibrosis are characterized by vimentin, alpha-SMA and Thy-1 expressions, and the
      cells might be generated from the pericytes or perifollicular dermal sheath cells
      in the lineage of stroma-/bone marrow-stem cells.

PMID- 22374730
TI  - C-reactive protein levels are associated with the progression of atherosclerotic
      lesions in rabbits.
AB  - Elevated plasma levels of C-reactive protein (CRP) are associated with increased
      risk of cardiovascular disease. CRP immunoreactive protein is also detected in
      the lesions of atherosclerosis. However, it is not known whether the CRP contents
      of atherosclerotic lesions are associated with the initiation and progression of
      atherosclerosis. To examine this hypothesis, we investigated different types of
      atherosclerotic lesions of rabbits fed with a cholesterol-rich diet for 6, 12,
      16, and 28 weeks and examined their relationship with CRP. We measured the aortic
      atherosclerotic area, macrophages, and smooth muscle cells along with CRP
      contents in the lesions. Atherosclerotic lesions of aortas began to form at 6
      weeks and were characterized by accumulation of macrophages in the intima, and
      lesions became more fibrotic in the advanced stage. Both plasma CRP levels and
      the lesional CRP contents were associated with the lesion size. Our results
      suggest that plasma CRP, as well as lesional CRP, associated with the formation
      and progression of atherosclerotic lesions.

PMID- 22374731
TI  - Turban pin aspiration: new fashion, new syndrome.
AB  - OBJECTIVES/HYPOTHESIS: Turban pin aspiration syndrome is a new clinical entity
      afflicting young Islamic girls wearing a turban.The goal of this study was to
      present our experience in diagnosis and treatment of this new entity, define its
      clinical and epidemiologic features, and shed a new light on the role of fashion
      in the increased incidence. STUDY DESIGN: A retrospective study in a tertiary
      university hospital. METHODS: Review of clinical parameters and epidemiologic
      features of 26 patients diagnosed with turban pin aspiration syndrome admitted to
      the Hadassah-Hebrew University Hospitals in Jerusalem from 1990 to 2010. RESULTS:
      All patients were Muslim females with an average age of 16 years. In all cases,
      the history was positive for accidental aspiration. Most of the pins were located
      in the trachea (42%). In 20 cases, the pins were extracted by rigid bronchoscopy
      without major complications. Fluoroscopy-assisted rigid bronchoscopy was used
      successfully in three cases. In one case, the object was self-ejected by coughing
      before the bronchoscopy, and two patients were referred to the chest unit for
      thoracotomy. CONCLUSIONS: Clinicians should be aware of this distinct form of
      foreign body aspiration, its method of diagnosis, and extraction techniques. A
      cultural investigation showed a difference in the turban-fastening technique of
      young girls as compared with their mothers. Removal by rigid bronchoscopy is a
      safe method with a high success rate and should be considered as the preferred
      extraction method of choice.

PMID- 22374732
TI  - Psychosexual distress in women with gynecologic cancer: a feasibility study of an
      online support group.
AB  - OBJECTIVES: The psychosexual concerns of gynecologic cancer patients are often
      unaddressed and there are limited resources available for women to deal with this
      highly sensitive topic. This feasibility study examines the participation rates
      and preliminary outcomes for an online support group designed specifically for
      women who are sexually distressed subsequent to gynecologic cancer treatment
      METHODS: A 12-week online intervention was developed to address the psychosexual
      impact of gynecologic cancer. This intervention included a professionally
      moderated, asynchronous discussion forum as well as the provision of psycho
      educational materials addressing the psychosexual impact of gynecologic cancer.
      Each week, a new topic was introduced and relevant material was posted on the
      website. Women were encouraged to share their experiences related to the topic.
      Twenty-seven, sexually distressed, remitted gynecologic cancer patients were
      randomly assigned to immediate treatment or a waitlist control condition.
      Participants completed questionnaires at baseline, 4-month and 8-month follow-ups
      assessing sexual distress as the primary outcome as well as anxiety, depression,
      and illness intrusiveness. RESULTS: Participation rates differed between the two
      groups, with greater participation occurring in the second group. Exit interviews
      indicated that the majority of the participants were satisfied with the
      intervention. Intent-to-treat analyses suggest a small effect for reduction in
      sexual distress CONCLUSIONS: This feasibility study suggests that women find this
      intervention acceptable. Further research is required to determine efficacy.

PMID- 22374733
TI  - Organophosphorus hydrolase as an in vivo catalytic nerve agent bioscavenger.
AB  - The use of proteins as a treatment for organophosphorus intoxication has been
      investigated since A. R. Main demonstrated protective efficacy against parathion
      with an exogenously administered arylesterase in the late 1950s. His experiments
      spurred over 60 years of research and progress in the development of enzymes as
      potential bioscavengers of nerve agents and pesticides. Efforts have been made to
      broaden the specificity of enzymes to make a universal scavenger that would
      protect against multiple compounds, and an understanding of the differential
      isomer toxicity of these compounds has provided the impetus for rational and
      random mutagenic approaches in the stereospecific design of enzymes. As improved
      candidate enzymes are continually developed, our understanding of the
      contributions of the catalytic parameters (k(cat) , K(M) and catalytic
      efficiency) to efficacy expands. In addition to the scavenging properties of the
      proteins, another important aspect of development is the pharmacokinetic profile
      of the drug product. Immunogenicity, absorption, distribution and elimination
      contribute significantly to the level of protection afforded by the protein. A
      review of the development of organophosphorus hydrolase (OPH) for use as in vivo
      catalytic bioscavengers is presented here.

PMID- 22374734
TI  - Preparation of 2-azarhodacyclobutanes by rhodium(I)-olefin oxidation.

PMID- 22374735
TI  - Pharmacokinetics, distribution and excretion of YM155 monobromide, a novel small
      molecule survivin suppressant, in male and pregnant or lactating female rats.
AB  - YM155 monobromide is a novel small-molecule survivin suppressant. The
      pharmacokinetics, distribution and excretion of YM155/[14C]YM155 were
      investigated using males and pregnant or lactating female rats after a single
      intravenous bolus administration. For the 0.1, 0.3 and 1 mg/kg YM155 doses given
      to male rats, increases in area under the plasma concentration-time curves were
      approximately proportional to the increase in the dose level. After administering
      [14C]YM155, radioactivity concentrations in the kidney and liver were highest
      among the tissues in both male and pregnant rats: e.g. 14.8- and 5.24-fold,
      respectively, and higher than in plasma at 0.1 h after dosing to male rats. The
      YM155 concentrations in the brain were lowest: 25-fold lower than in plasma. The
      transfer of radioactivity into fetuses was low (about 2-fold lower than in
      plasma). In lactating rats, the radioactivity was transferred into milk at a
      level 8- to 21-fold higher than for plasma. Radioactivity was primarily excreted
      in feces (64.0%) and urine (35.2%). The fecal excretion was considered to have
      occurred mainly by biliary excretion and partly by secretion across the
      gastrointestinal membrane from the blood to the lumen.

PMID- 22374736
TI  - Enzymatically induced mineralization of platelet-rich fibrin.
AB  - Membranes of the autologous blood-derived biomaterial platelet-rich fibrin (PRF)
      were functionalized by incorporation of alkaline phosphatase (ALP), an enzyme
      involved in mineralization of bone, and subsequently incubated in calcium
      glycerophosphate (CaGP) solution to induce PRFs mineralization with calcium
      phosphate (CaP) to improve PRFs suitability as a material for bone replacement.
      Incorporated ALP retained its bioactivity and induced formation of CaP material
      within PRF membranes, as confirmed by SEM, EDS, FTIR, and von Kossa staining. The
      mass percentage attributable to CaP was quantified by lyophilization and
      measurement of the remaining mass fraction as well as by TGA. Cytocompatibility
      tests (LDH, MTT, and WST) with SAOS-2 cells showed that mineralized PRF did not
      release substances detrimental to cell vitality. Live/dead staining and SEM
      showed that mineralized PRF was colonized by cells. The results show that
      hydrogel biomaterials such as PRF can be mineralized through functionalization
      with ALP.

PMID- 22374737
TI  - Analysis of the sensory innervations of the greater trochanter for improving the
      treatment of greater trochanteric pain syndrome.
AB  - In medical practice, greater trochanteric pain syndrome has an incidence of 5.6
      per 1,000 adults per year, and affects up to 25% of patients with knee
      osteoarthritis and low back pain in industrialized nations. It also occurs as a
      complication after total hip arthroplasty. Different etiologies of the pain
      syndrome have been discussed, but an exact cause remains unknown. The purpose of
      this study was to obtain a better understanding of the sensory innervations of
      the greater trochanter in attempt to improve the treatment of this syndrome.
      Therefore, we dissected the gluteal region of seven adult and one fetal formalin
      fixed cadavers, and both macroscopic and microscopic examination was performed.
      We found a small sensory nerve supply to the periosteum and bursae of the greater
      trochanter. This nerve is a branch of the n. femoralis and accompanies the
      arteria and vena circumflexa femoris medialis and their trochanteric branches to
      the greater trochanter. This nerve enters the periosteum of the greater
      trochanter directly caudal to the tendon of the inferior gemellus muscle. This
      new anatomical information may be helpful in improving therapy, such as
      interventional denervation of the greater trochanter or anatomically guided
      injections with corticosteroids and local anesthetics.

PMID- 22374738
TI  - Mediators of receptor tyrosine kinase activation in infantile fibrosarcoma: a
      Children's Oncology Group study.
AB  - Infantile fibrosarcoma (IFS; also known as cellular congenital mesoblastic
      nephroma, CMN, when in the kidney) is a rare, undifferentiated tumour often
      characterized by the ETV6-NTRK3 fusion transcript. Our goal was to identify
      downstream pathways, diagnostic markers and potential therapeutic targets for
      IFS/CMN. Global gene expression, reverse-phase protein array and ETV6-NTRK3
      fusion analyses were performed on 14 IFS/CMN and compared with 41 other
      paediatric renal tumours. These analyses confirm significant receptor tyrosine
      kinase (RTK) activation, with evidence of PI3-Akt, MAPK and SRC activation. In
      particular, GAB2 docking protein, STAT5-pTyr-694, STAT3-pSer-729 and YAP-pSer-127
      were elevated, and TAZ-pSer-89 was decreased. This provides mRNA and proteomic
      evidence that GAB2, STAT activation and phosphorylation of the Hippo pathway
      transcription co-activators YAP and TAZ contribute to the RTK signal transduction
      in IFS/CMN. All IFS/CMN tumours displayed a distinctive gene expression pattern
      that may be diagnostically useful. Unexpectedly, abundant ETV6-NTRK3 transcript
      copies were present in only 7/14 IFS, with very low copy number in 3/14. An
      additional 4/14 were negative by RT-PCR and absence of ETV6-NTRK3 was confirmed
      by FISH for both ETV6 and NTRK3. Therefore, molecular mechanisms other than ETV6
      NTRK3 fusion are responsible for the development of some IFS/CMNs and the absence
      of ETV6-NTRK3 fusion products should not exclude IFS/CMN as a diagnosis.

PMID- 22374739
TI  - Expansion of the lysine acylation landscape.
AB  - Leaving marks: the number of known posttranslational modifications for lysine has
      been expanded considerably. In addition to acetylation of side-chain amino
      functionalities of lysine residues in proteins, crotonylation, succinylation, and
      malonylation have now been identified as posttranslational modifications in
      histone and in non-histone proteins.

PMID- 22374740
TI  - Ongoing problems with metal-on-metal hip implants.

PMID- 22374741
TI  - How safe are metal-on-metal hip implants?

PMID- 22374742
TI  - Directed remote aromatic metalations: mechanisms and driving forces.
AB  - Directed remote aromatic metalations are useful synthetic transformations
      allowing for rapid regioselective access to elaborate highly substituted
      carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle
      of data reported on directed remote aromatic metalations. Through a careful
      analysis of critically selected examples, advanced rationalizations of remote
      metalation regioselectivities are presented. These extend beyond the complex
      induced proximity effect (CIPE). Mechanisms, driving forces, and parameters
      influencing remote metalations are discussed. An understanding of these
      metalation mechanisms enables more accurate predictability of justification of
      regiochemical outcomes of these useful synthetic transformations.

PMID- 22374743
TI  - Anaerobic and microaerophilic pathogens in the biofilm formation on voice
      prostheses: A pilot study.
AB  - OBJECTIVES/HYPOTHESIS: Voice rehabilitation with voice prostheses is a standard
      therapy in laryngectomized patients. Biofilm formation on the surface of the
      voice prostheses causes device failure and requires frequent replacements.
      Studies analyzing the biofilm of voice prostheses have mainly focused on aerobic
      bacteria. Anaerobic bacteria as an integral part of the biofilms on voice
      prostheses have not been investigated yet. STUDY DESIGN: Prospective pilot study
      on the occurrence of anaerobic and microaerophilic pathogens in biofilm formation
      on voice prostheses. METHODS: Biofilm samples of 15 voice prostheses were
      analyzed using a polymerase chain reaction-based hybridization method regarding
      the presence of 11 selected anaerobic and microaerophilic pathogens. RESULTS: In
      80% of the voice prostheses, at least one and up to 10 of the tested bacteria
      could be identified. Fusobacterium nucleatum was the pathogen most often present
      (73%). Other frequently occurring pathogens were Treponema denticola (40%),
      Tannerella forsythia (33%), and Eikenella corrodens (33%). There was no
      correlation between the number of identified bacteria and the indwelling times
      (mean, 127 days; maximum, 344 days; minimum, 22 days). CONCLUSIONS: For the first
      time, anaerobic and microaerophilic pathogens have been identified as part of the
      biofilm formation on the surface of voice prostheses. Those pathogens might be
      responsible for accelerated biofilm formation and reduced lifetime of the voice
      prostheses.

PMID- 22374744
TI  - A function for all posterior Hoxd genes during digit development?
AB  - BACKGROUND: Four posterior Hoxd genes, from Hoxd13 to Hoxd10, are collectively
      regulated during the development of tetrapod digits. Besides the well-documented
      role of Hoxd13, the function of the neighboring genes has been difficult to
      evaluate due to the close genetic linkage and potential regulatory interferences.
      We used a combination of five small nested deletions in cis, involving from two
      to four consecutive genes of the Hoxd13 to Hoxd9 loci, in mice, to evaluate their
      combined functional importance. RESULTS: We show that deletions leading to a gain
      of function of Hoxd13, via regulatory re-allocation, generate abnormal
      phenotypes, in agreement with the dominant negative role of this gene. We also
      show that Hoxd10, Hoxd11, and Hoxd12 all seem to play a genuine role in digit
      development, though less compelling than that of Hoxd13. In contrast, the nearby
      Hoxd9 contributed no measurable function in digits. CONCLUSIONS: We conclude that
      a slight and transient deregulation of Hoxd13 expression can readily affect the
      relative lengths of limb segments and that all posterior Hoxd genes likely
      contribute to the final limb morphology. We discuss the difficulty to clearly
      assess the functional share of individual genes within such a gene family, where
      closely located neighbors, coding for homologous proteins, are regulated by a
      unique circuitry and all contribute to shape the distal parts of our appendages.

PMID- 22374745
TI  - Expression of neural and neurotrophic markers in nucleus pulposus cells isolated
      from degenerated intervertebral disc.
AB  - Intervertebral disc (IVD) degeneration is a common disorder of the lower spine.
      Since it is caused by loss of cellularity, there is interest in the comprehension
      of the cellular phenotypes. This study aimed to verify if stem cells isolated
      from nucleus pulposus of intervertebral discs (NPs-IVD), which may express
      neurogenic properties, may be implicated in IVD disease. NPs-IVD isolated from 14
      human pathological discs were cultured under mesenchymal and neural
      differentiation. An induction of the neural markers GFAP, NF, MAP2, O4, and a
      decrement of the expression of the immature neural markers beta-tubulin III,
      Nestin, NG2, occurred within the neural differentiation. The expression of TrkA
      and p75NGFR, the receptors of NGF, was not correlated with neural induction; in
      contrast, TrkB, the BDNF receptor, increased and was co-expressed with acid
      sensing ion channel 3 (ASIC3). In the same condition, neuroinflammatory markers
      were over-expressed. We confirm our hypothesis that stem cells within IVD
      degeneration acquire neurogenic phenotype, causing the induction of markers
      related to inflammatory condition. These cells could promote the enrolment of
      neurotrophines in adaptation to the acidic microenvironment in degenerative
      conditions. These data could improve our knowledge about IVD cellularity and
      eventually lead to the development of pharmacological therapies.

PMID- 22374746
TI  - Overexpression of IgLON cell adhesion molecules changes proliferation and cell
      size of cortical astrocytes.
AB  - IgLON family is a subgroup of the immunoglobulin superfamily cell adhesion
      molecules and composed of limbic system-associated protein (LAMP), opioid binding
      cell adhesion molecule (OBCAM), neurotrimin (Ntm) and Kilon. In the present
      study, we investigated the overexpression of LAMP, OBCAM, Ntm and Kilon on the
      proliferation and cell size of type-1 astrocytes in vitro. Quantitative analysis
      using bromodeoxyuridine immunocytochemistry revealed that the expression of OBCAM
      had greater inhibitory effect on astrocytic proliferation as compared with LAMP,
      Ntm and Kilon ones. OBCAM overexpression increased the cell size of astrocytes as
      compared with the control. The treatment of FGF-2 had greater proliferative
      effect on OBCAM-transfected astrocytes as compared with the control. These
      results suggest that OBCAM is more potent regulator for controlling the
      proliferation and cell size of astrocytes as compared with other IgLON proteins
      possibly through FGF-2 receptor-mediated pathway.

PMID- 22374747
TI  - A fresh look at adenosine-binding DNA motifs.

PMID- 22374748
TI  - Differentiation of methylbenzylpiperazines (MBPs) and benzoylpiperazine (BNZP)
      using GC-MS and GC-IRD.
AB  - Three-ring substituted methylbenzylpiperazines (MBPs) and their isobaric
      benzoylpiperazine (BNZP) have equal mass and many common mass spectral fragment
      ions. The mass spectrum of BNZP yields a unique benzoyl-group containing fragment
      at m/z 122 and an additional major fragment at m/z 69 that allows its
      discrimination from the three MBP regioisomers. Perfluoroacylation of the
      secondary amine nitrogen of these isomeric piperazines gave mass spectra with
      differences in relative abundance of some fragment ions but acylation does not
      alter the fragmentation pathway and did not provide additional MS fragments of
      discrimination among these isomers. Gas chromatography coupled with infrared
      detection (GC-IRD) provides direct confirmatory data for the structural
      differentiation between the four isomers. The mass spectra in combination with
      the vapour phase IR spectra provide for specific confirmation of each of the
      isomeric piperazines. The underivatized and perfluoroacyl derivatives of these
      four piperazines were resolved on a stationary phase of 100% trifluoropropyl
      methyl polysiloxane (Rtx-200). Gas chromatography coupled with time-of-flight
      mass spectrometry provides an additional means of differentiating between the
      isobaric MBP and BNZP which have equivalent nominal masses but are different in
      their elemental composition and exact masses.

PMID- 22374751
TI  - A stable hybrid bisphosphonate polyoxometalate single-molecule magnet.

PMID- 22374749
TI  - Epigenetic disruption of cadherin-11 in human cancer metastasis.
AB  - Little is known about the molecular events occurring in the metastases of human
      tumours. Epigenetic alterations are dynamic lesions that change over the natural
      course of the disease, and so they might play a role in the biology of cancer
      cells that have departed from the primary tumour. Herein, we have adopted an
      epigenomic approach to identify some of these changes. Using a DNA methylation
      microarray platform to compare paired primary tumour and lymph node metastatic
      cell lines from the same patient, we observed cadherin-11 promoter CpG island
      hypermethylation as a likely target of the process. We found that CDH11 DNA
      methylation-associated transcriptional silencing occurred in the corresponding
      lymph node metastases of melanoma and head and neck cancer cells but not in the
      primary tumours. Using in vitro and in vivo cellular and mouse models for
      depleted or enhanced CDH11 activity, we also demonstrated that CDH11 acts as an
      inhibitor of tumour growth, motility and dissemination. Most importantly, the
      study of CDH11 5'-CpG island hypermethylation in primary tumours and lymph node
      metastases of cancer patients showed this epigenetic alteration to be
      significantly confined to the disseminated cells. Overall, these results indicate
      the existence of metastasis-specific epigenetic events that might contribute to
      the progression of the disease.

PMID- 22374752
TI  - Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering
      via mineralization of gelatin hydrogel and study of mineral transformation in
      simulated body fluid.
AB  - In this study, double diffusion method in a physiologically relevant environment
      was used to prepare a biomimetic gelatin-amorphous calcium phosphate
      nanocomposite scaffold. The precipitated calcium phosphate within gelatin as well
      as produced nanocomposite scaffolds were characterized by the commonly used bulk
      techniques. The results showed that nanocomposite scaffolds were porous with
      three-dimensionally interconnected microstructure, pore size ranging from 150 to
      350 MUm. Porosity was about 82% and nanocrystalline precipitated minerals were
      dispersed evenly among gelatin fibers. A mineral containing amorphous calcium
      phosphate and brushite precipitate was formed within the gelatin matrix at 4
      degrees C. After incubation in SBF solution at 37 degrees C for 5 days, the
      mineral phase was transformed to nanocrystalline hydroxyapatite. It should be
      noted that precursor phases inside a scaffold implanted into the body can result
      in biomimetic conversion of precursors to hydroxyapatite that is very similar to
      the bone mineral and has a profound level of biocompatibility. Thus, our results
      highlight the potential use of engineered biomimetic bone tissue scaffolds in the
      bone tissue repair process.

PMID- 22374753
TI  - Determinants of evolving metabolic and cardiovascular benefit/risk profiles of
      rosiglitazone therapy during the natural history of diabetes: molecular
      mechanisms in the context of integrated pathophysiology.
AB  - Rosiglitazone is a thiazolidinedione, a synthetic PPARgamma receptor agonist with
      insulin-sensitizing properties that is used as an antidiabetic drug. In addition
      to improving glycemic control through actions in metabolic target tissues,
      rosiglitazone has numerous biological actions that impact on cardiovascular
      homeostasis. Some of these actions are helpful (e.g., improving endothelial
      function), whereas others are potentially harmful (e.g., promoting fluid
      retention). Since cardiovascular morbidity and mortality are major endpoints for
      diabetes, it is essential to understand how the natural history of diabetes
      alters the net benefits and risks of rosiglitazone therapy. This complex issue is
      an important determinant of optimal use of rosiglitazone and is critical for
      understanding cardiovascular safety issues. We give special attention to the
      effects of rosiglitazone in diabetic patients with stable coronary artery disease
      and the impact of rosiglitazone actions on atherosclerosis and plaque
      instability. This provides a rational conceptual framework for predicting
      evolving benefit/risk profiles that inform optimal use of rosiglitazone in the
      clinical setting and help explain the results of recent large clinical
      intervention trials where rosiglitazone had disappointing cardiovascular
      outcomes. Thus, in this perspective, we describe what is known about the
      molecular mechanisms of action of rosiglitazone on cardiovascular targets in the
      context of the evolving pathophysiology of diabetes over its natural history.

PMID- 22374754
TI  - Influence of maternal metabolism and parental genetics on fetal maldevelopment in
      diabetic rat pregnancy.
AB  - The purpose of this study was to investigate the influence of parental
      transgenerational genetics and maternal metabolic state on fetal maldevelopment
      in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain,
      and an inbred malformation-prone (L) strain, were cross-mated to produce two
      different F(1) hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and
      LW females were mated with normal males of the same F(1) generation to obtain
      WLWL and LWLW F(2) hybrids. Maternal diabetes increased malformation and
      resorption rates in both F(2) generations. MD-WLWL offspring had higher
      resorption rate but similar malformation rate compared with the MD-LWLW
      offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia,
      whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft
      lip and palate. The MD-WL dams showed increased beta-hydroxybutyrate levels and
      alterations in concentrations of several amino acids (taurine, asparagine,
      citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared
      with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity
      and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene
      expression of reactive oxygen species (ROS) scavenger enzymes was diminished in
      MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and
      Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW
      fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic
      hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical
      autosomal genotypes, the WL and LW dams gave birth to offspring with markedly
      different malformation patterns. Together with fetal differences in enzymatic
      activity and expression of Gapdh, ROS scavengers, and developmental genes, these
      results may suggest a teratological mechanism in diabetic pregnancy influenced by
      maternal metabolism and parental strain epigenetics.

PMID- 22374755
TI  - Serotonergic effects on feeding, but not hypothalamus-pituitary-adrenal
      secretion, are altered in ovine pregnancy.
AB  - In ovine pregnancy, as in human pregnancy, hypothalamus-pituitary-adrenal
      activity is chronically increased. These studies were designed to test the
      hypotheses that expression of serotonergic genes and responsiveness to serotonin
      are increased in pregnancy. We tested the stimulatory effect of an acute,
      intracerebroventricular injection of the serotonin reuptake inhibitor fluoxetine
      on plasma ACTH and cortisol in ewes during late pregnancy or postpartum. We also
      tested the effect of lower-dose, longer-term stimulation by
      intracerebroventricular infusion of fluoxetine in pregnant and nonpregnant ewes
      over 6 days. Overall, we found that the stimulatory effect of fluoxetine on ACTH
      and cortisol was not significantly different between late-gestation and
      nonpregnant ewes, although the effect of acute fluoxetine administration was
      inversely related to plasma progesterone concentrations. Also, there were no
      differences in hypothalamic expression of the glucocorticoid and
      mineralocorticoid receptors, corticotropin-releasing hormone, AVP, the serotonin
      reuptake transporter, or the serotonin [5-hydroxytryptamine (5-HT)] receptors 5
      HT(1A) and 5-HT(2A) with pregnancy or fluoxetine treatment. However, chronic
      fluoxetine infusion reduced food intake in the nonpregnant, but not pregnant,
      ewes. Expression of proopiomelanocortin mRNA in the hypothalamus was reduced in
      pregnant compared with nonpregnant ewes. Our results indicate that pregnancy does
      not increase responsiveness of ACTH and cortisol to serotonergic stimulation but,
      rather, that progesterone reduces the ACTH response. In addition, we found a
      reduced ability of serotonin to inhibit feeding in the pregnant ewes, consistent
      with a reduction in anorexic mechanisms in the pregnant state.

PMID- 22374756
TI  - Repeated immobilization stress disturbed steroidogenic machinery and stimulated
      the expression of cAMP signaling elements and adrenergic receptors in Leydig
      cells.
AB  - This study was designed to evaluate the effect of acute (2 h daily) and repeated
      (2 h daily for 2 or 10 consecutive days) immobilization stress (IMO) on: 1) the
      steroidogenic machinery homeostasis; 2) cAMP signaling; and the expression of
      receptors for main markers of 3) adrenergic and 4) glucocorticoid signaling in
      Leydig cells of adult rats. The results showed that acute IMO inhibited
      steroidogenic machinery in Leydig cells by downregulation of Scarb1 (scavenger
      receptor class B), Cyp11a1 (cholesterol side-chain cleavage enzyme), Cyp17a1
      (17alpha-hydroxylase/17,20 lyase), and Hsd17b3 (17beta-hydroxysteroid
      dehydrogenase) expression. In addition to acute IMO effects, repeated IMO
      increased transcription of Star (steroidogenic acute regulatory protein) and
      Arr19 (androgen receptor corepressor 19 kDa) in Leydig cells. In the same cells,
      the transcription of adenylyl cyclases (Adcy7, Adcy9, Adcy10) and cAMP-specific
      phosphodiesterases (Pde4a, Pde4b, Pde4d, Pde7a, Pde8a) was stimulated, whereas
      the expression of the genes encoding protein kinase A subunits were unaffected.
      Ten times repeated IMO increased the levels of all adrenergic receptors and beta
      adrenergic receptor kinase (Adrbk1) in Leydig cells. The transcription analysis
      was supported by cAMP/testosterone production. In this signaling scenario,
      partial recovery of testosterone production in medium/content was detected. The
      physiological significance of the present results was proven by ex vivo
      application of epinephrine, which increased cAMP/testosterone production by
      Leydig cells from control rats in greater fashion than from stressed. IMO did not
      affect the expression of transcripts for Crhr1/Crhr2 (corticotropin releasing
      hormone receptors), Acthr (adrenocorticotropin releasing hormone receptor), Gr
      (glucocorticoid receptor), and Hsd11b1 [hydroxysteroid (11-beta) dehydrogenase
      1], while all types of IMO stimulated the expression of Hsd11b2, the
      unidirectional oxidase with high affinity to inactivate glucocorticoids. Thus,
      presented data provide new molecular/transcriptional base for "fight/adaptation"
      of Leydig cells and new insights into the role of cAMP, epinephrine, and
      glucocorticoid signaling in recovery of stress-impaired Leydig cell
      steroidogenesis.

PMID- 22374757
TI  - TrkB receptor signaling in the nucleus tractus solitarius mediates the food
      intake-suppressive effects of hindbrain BDNF and leptin.
AB  - Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute
      to the central nervous system (CNS) control of energy balance. The role of
      hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined
      here. Hindbrain ventricular BDNF suppressed body weight through reductions in
      overall food intake and meal size and by increasing core temperature. To localize
      the neurons mediating the energy balance effects of hindbrain ventricle-delivered
      BDNF, ventricle subthreshold doses were delivered directly to medial nucleus
      tractus solitarius (mNTS). mNTS BDNF administration reduced food intake
      significantly, and this effect was blocked by preadministration of a highly
      selective TrkB receptor antagonist {[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl
      benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor
      activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and
      leptin interact with melanocortin signaling to reduce food intake, we also
      examined whether the intake inhibitory effects of hindbrain leptin involve
      hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal
      vagal complex of the hindbrain was increased significantly by hindbrain leptin
      delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin
      signaling in the control of energy balance, leptin and ANA-12 were coadministered
      into the mNTS. Administration of the TrkB receptor antagonist attenuated the
      intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor
      activation contributes to the mediation of the anorexigenic effects of hindbrain
      leptin. Collectively, these results indicate that TrkB-mediated signaling in the
      mNTS negatively regulates food intake and, in part, the intake inhibitory effects
      of leptin administered into the NTS.

PMID- 22374758
TI  - CB(1) antagonism restores hepatic insulin sensitivity without normalization of
      adiposity in diet-induced obese dogs.
AB  - The endocannabinoid system is highly implicated in the development of insulin
      resistance associated with obesity. It has been shown that antagonism of the
      CB(1) receptor improves insulin sensitivity (S(I)). However, it is unknown
      whether this improvement is due to the direct effect of CB(1) blockade on
      peripheral tissues or secondary to decreased fat mass. Here, we examine in the
      canine dog model the longitudinal changes in S(I) and fat deposition when obesity
      was induced with a high-fat diet (HFD) and animals were treated with the CB(1)
      antagonist rimonabant. S(I) was assessed (n = 20) in animals fed a HFD for 6 wk
      to establish obesity. Thereafter, while HFD was continued for 16 additional
      weeks, animals were divided into two groups: rimonabant (1.25 mg.kg(-1).day(-1)
      RIM; n = 11) and placebo (n = 9). Euglycemic hyperinsulinemic clamps were
      performed to evaluate changes in insulin resistance and glucose turnover before
      HFD (week -6) after HFD but before treatment (week 0) and at weeks 2, 6, 12, and
      16 of treatment (or placebo) + HFD. Magnetic resonance imaging was performed to
      determine adiposity- related changes in S(I). Animals developed significant
      insulin resistance and increased visceral and subcutaneous adiposity after 6 wk
      of HFD. Treatment with RIM resulted in a modest decrease in total trunk fat with
      relatively little change in peripheral glucose uptake. However, there was
      significant improvement in hepatic insulin resistance after only 2 wk of RIM
      treatment with a concomitant increase in plasma adiponectin levels; both were
      maintained for the duration of the RIM treatment. CB(1) receptor antagonism
      appears to have a direct effect on hepatic insulin sensitivity that may be
      mediated by adiponectin and independent of pronounced reductions in body fat.
      However, the relatively modest effect on peripheral insulin sensitivity suggests
      that significant improvements may be secondary to reduced fat mass.

PMID- 22374760
TI  - [Presentation].

PMID- 22374759
TI  - Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in
      human placenta and in human placental trophoblasts.
AB  - The human placenta is key to pregnancy outcome, and the elevated oxidative stress
      present in many complicated pregnancies contributes to placental dysfunction and
      suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice,
      which is rich in polyphenolic antioxidants, limits placental trophoblast injury
      in vivo and in vitro. Pregnant women with singleton pregnancies were randomized
      at 35~38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo)
      until the time of delivery. Placental tissues from 12 patients (4 in the
      pomegranate group and 8 in the control group) were collected for analysis of
      oxidative stress. The preliminary in vivo results were extended to oxidative
      stress and cell death assays in vitro. Placental explants and cultured primary
      human trophoblasts were exposed to pomegranate juice or glucose (control) under
      defined oxygen tensions and chemical stimuli. We found decreased oxidative stress
      in term human placentas from women who labored after prenatal ingestion of
      pomegranate juice compared with apple juice as control. Moreover, pomegranate
      juice reduced in vitro oxidative stress, apoptosis, and global cell death in term
      villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia
      mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but
      not ellagic acid, both prominent polyphenols in pomegranate juice, reduced
      oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts.
      We conclude that pomegranate juice reduces placental oxidative stress in vivo and
      in vitro while limiting stimulus-induced death of human trophoblasts in culture.
      The polyphenol punicalagin mimics this protective effect. We speculate that
      antenatal intake of pomegranate may limit placental injury and thereby may confer
      protection to the exposed fetus.

PMID- 22374761
TI  - [Diagnosis and treatment of attention deficit hyperactivity disorder in adults].
AB  - AIM: To review the latest data available concerning the diagnosis and treatment
      of adults with attention deficit hyper-activity disorder (ADHD). DEVELOPMENT AND
      CONCLUSIONS: A number of different instruments for evaluating ADHD have been
      adapted to the adult patient and allow a reliable diagnosis of the disorder to be
      reached. Semi-structured interviews, like the Diagnostisch Interview Voor ADHD
      2.0 (DIVA), simplify the task of performing a rigorous evaluation of both the
      symptoms of the disorder in adulthood and the dysfunctions generated by ADHD.
      Quick screening instruments that allow better detection of ADHD in adults, such
      as the Adult Self-Report Scale 1.1 (ASRS), have been validated. In recent years,
      there has been a notable increase in the number of studies focused on ADHD in
      adults and that research has provided solid data regarding the safety and
      effectiveness of different treatments. According to the recommendations of the
      European Consensus statement by the European Network Adult ADHD, the treatment
      ought to be multimodal, which means combining pharmacological interventions with
      psychological and psychosocial ones. Methylphenidate displays a high degree of
      effectiveness and safety in the treatment of adults at doses of around 1
      mg/kg/day. Amphetamines, such as lisdexamphetamine, have also proved to be
      effective in the treatment of adults with ADHD. Among non-stimulant treatments,
      atomoxetine has proved to be effective and safe in adults in doses of about 80
      100 mg/day. Excellent studies have been conducted on the cognitive-behavioural
      treatment of adults with ADHD, the results of which highlight its effectiveness
      in both the short and the long term.

PMID- 22374762
TI  - [Short-lived disorders].
AB  - Over the years, most of the mental disorders that are dealt with in everyday
      clinical practice have changed not only their names but also their
      conceptualisation. Furthermore, as some disorders disappear or are forgotten,
      others come into being. Seen from a historical perspective and unlike many of the
      diseases included within classical medicine, it can be stated that one of the
      basic characteristics of mental disorders is their short-lived presence in the
      scientific literature. In this study we analyse the causes underlying the
      transitory nature of mental disorders. The disappearance of a disorder or the
      modification of how it is conceptualised may be linked to several different
      motives. Sometimes they may be due to an evolution of the construct, as a result
      of new findings. On other occasions the disorder falls into disuse owing to the
      weakness of the theoretical construct or the clinical research upholding it.
      Lastly, because the Diagnostic and Statistical Manual of Mental Disorders and the
      International Classification of Diseases require updates that incorporate new
      contributions and correct faults in the current model, they give rise to new
      denominations and definitions in mental disorders. This article analyses these
      three situations and offers an illustrative example in each case.

PMID- 22374763
TI  - [Executive functions and stressful characteristics of children with attention
      deficit hyperactivity disorder: influence on behavioral problems during
      adolescence].
AB  - INTRODUCTION: The identification of possible factors that are influencing the
      course of attention-deficit hyperactivity disorder (ADHD) will allow the
      development of more effective early intervention strategies. AIMS. This research,
      which used a longitudinal and correlational design, set out to examine the
      temporal consistency of the primary symptoms and ADHD associated problems. In
      addition, the relationships and predictive power of working memory, inhibition
      and stressful characteristics of children with ADHD on the disorder symptoms and
      behavioral problems in adolescence was analyzed. SUBJECTS AND METHODS: This study
      included 65 families with children diagnosed with ADHD. In phase 1 children
      performed verbal working memory, visuo-spatial and inhibition tests, and
      information from parents about stressful characteristics of children was
      collected. In phase 1 and in the follow-up phase, which took place three years
      later, parents and teachers reported on the primary symptoms of ADHD and
      behavioral problems. RESULTS: Inattention symptoms as well as most behavioral
      problems were stable over time, while hyperactivity/impulsivity symptoms
      decreased. Moreover, neither working memory nor inhibition showed power to
      predict the central manifestations of ADHD or behavioral problems, while
      stressful characteristics of demandingness, low adaptability and negative mood
      had a moderate predictive capacity. CONCLUSION: These results confirm the role of
      stressful child characteristics as a risk factor in the course of ADHD.

PMID- 22374764
TI  - [Brain plasticity for language in children and adolescents].
AB  - INTRODUCTION: Plasticity makes possible adaptative modelling of the nervous
      system to experiences i.e. learning and development. AIM: To review current
      literature on clinical long term evolution and functional magnetic resonance
      imaging (fMRI) features of brain remodelling after focal stroke in left
      perisylvian regions involved in basic language processing during infancy and
      childhood. DEVELOPMENT: Each of the main neurocognitive subsystems develops with
      different timing, so altered plasticity and vulnerability are diverse, according
      with age at insult and its topography. Genetic programming makes human brain
      capable for installing basic formal linguistic abilities on an associative
      perisylvian subsystem, highly specialised. A focal lesion of this region leads to
      remodelling phenomena by disinhibition of contralateral frontal and perisylvian
      structures and by a more or less efficacious activation of neighboring
      homolateral cortex, as it has been shown by fMRI studies and DTI tractography. As
      a result, very early local stroke to language areas is generally well compensated
      in terms of linguistic behaviour. Meanwhile acquired aphasias into middle and
      late childhood, even if they have a better prognosis than in adults, they fail to
      resume without lexical access defaults and/or difficulties in written language.
      CONCLUSION: Brain plasticity can promote restoration and further development of
      language following a stroke in left peri-sylvian areas, specially when lesion
      occurs at perinatal to middle childhood.

PMID- 22374765
TI  - [Syntactic and textual complexity in children with attention deficit
      hyperactivity disorder].
AB  - INTRODUCTION AND AIMS: . In this work we analyse the syntax used by children
      diagnosed with attention deficit hyperactivity disorder (ADHD) when writing texts
      with a narrative and argumentative superstructure. The basic data analysed are
      the ratio of syntactic complexity and the relative distribution of verb tenses,
      assuming that in fusional languages like Spanish the TAM system (tense, aspect,
      mode) is the direct linguistic correlate of the executive functions related with
      the management of temporality. SUBJECTS AND METHODS: Children between 8 and 13
      years of age were asked to write narrative and argumentative texts; data were
      obtained in clinical contexts. The use of complex syntactic structures and verb
      conjugation were analysed both quantitatively and qualitatively. RESULTS AND
      CONCLUSIONS: The children with ADHD displayed lower values in terms of levels of
      syntactic complexity and used fewer subordinate clauses than the children in the
      control group in both types of texts. As far as verb tenses are concerned, they
      used a higher proportion of prototypical tenses, that is to say, the present
      simple in argumentation and the imperfect indicative in narrative texts.

PMID- 22374766
TI  - [Cortical organization of different languages with different proficiency levels].
AB  - INTRODUCTION: Several studies have enhanced differences and similarities in the
      processing of early and late acquired languages. Anatomic and functional
      differences have demonstrated how bilingualism exerts executive functions,
      dependent of the prefrontal cortex in the frontal lobe. AIM: To study the
      cortical differences, neurophysiologically measured in school-aged children, in
      the processing of known and unknown languages. SUBJECTS AND METHODS: We have
      measured the recognition processes of words in several languages, specifically
      Spanish, English, Portuguese and Mandarin Chinese, as well as their event-related
      potentials (ERP) correlates in 10 year-old children. RESULTS: The greater
      knowledge of a language (in our study, Spanish) associates shorter latencies in
      ERP and a greater activity in both early (N200) and late (N400) components of
      temporal regions, demonstrating both a direct relation between practice and speed
      of processing of the language and the consolidation of the linguistic information
      in the temporal lobe, while less familiar or unknown languages show longer
      latencies and a greater involvement of posterior brain areas, as well as a
      different lateralization probably due to a higher effort put on its integration,
      mostly in late processing stages of linguistic information, which ultimately
      reflects a clear effect of the neuroplasticity generated by practice, as more
      efficient and stable neural networks are created after being trained for a long
      time, in contrast with what occurs with those which have not been sufficiently
      stimulated. CONCLUSION: Mandarin Chinese's organization in the brain cortex shows
      bilateral with right dominant lateralization as well as longer ERP latencies.

PMID- 22374767
TI  - [Clinical usefulness of the classifications of developmental language disorders].
AB  - There have been several proposals for the classification of language disorders in
      children; some of them are based on the desire to differentiate in terms of its
      possible cause, while others are based on the criteria for symptoms grouping
      ('syndromes'), in order to facilitate the diagnostic process and orientate some
      intervention programs. In the first part, there is an analysis of the advantages
      and limitations of the most popular classifications, pointing to the inaccuracy
      on description basis and to the inability to distinguish between several
      subgroups. In the second part, it is analysed the clinical purpose of using these
      nomenclatures. Finally, the idea of using a clinical tool is proposed, in order
      to include the severity criteria of symptoms in the differential diagnosis.

PMID- 22374769
TI  - [High intellectual capacity: perfectionism and metacognitive regulation].
AB  - The aim of this study is a better understanding of the high intellectual
      abilities. From the emergent paradigm, high intellectual abilities are understood
      as multidimensional and as the result of the life-span development, this is to
      say, not only the result of their neurobiological bases but of the interrelation
      among opportunity, personality, psychosocial factors and individual effort. This
      theoretical study analyses the differences between excellence and perfectionism,
      their types and incidence on high intellectual ability functioning. We propose a
      comparative view of the state of the art through recent research and their
      results referred to different types of perfectionism, their measure and relation
      with high intellectual abilities, its metacognitive regulation and its goal
      orientation. Finally, we propose a starting research comparing the relationship
      between perfectionism as a multidimensional cognitive pattern of functioning
      (positive or negative) and the measures of metacognitive performance.

PMID- 22374770
TI  - [Study on the professional procedures, experiences and needs of parents when they
      are told their child has a disability or developmental disorder. Breaking the
      news].
AB  - INTRODUCTION: Both the moment and the way chosen to break the news that a child
      aged 0-6 years is suffering, or may suffer, from a developmental disorder or
      disability have an effect on the parents and on the familial system that goes
      beyond the actual fact of knowing about the circumstance in itself. It is a very
      significant social act that represents the first encounter in which the parents
      explore and anticipate the social attitudes of inclusion or exclusion towards the
      child. AIMS: To gather information about the practices usually employed by
      professionals when it comes to breaking the news to the families, to evaluate
      what aspects of the process could be improved, to determine the families' needs
      in these circumstances and to gain a deeper understanding of the affective
      emotional processes experienced by the parents. SUBJECTS AND METHODS: The
      research was conducted using a questionnaire with 43 items, which was
      specifically designed for the population under examination in the study.
      Altogether, 418 parents from 15 different autonomous regions of Spain took part
      in the study. At the same time, the existing literature on diagnostic information
      in Spanish was reviewed. RESULTS AND CONCLUSIONS: It can be concluded that, to
      'break the bad news', professionals must know the family; they must take the
      utmost care in choosing when, where and how to give that news; the parents must
      be together when they are told; and they must take into account the type of
      disability the child suffers from as well as its intensity. These guidelines of
      conduct become manifest in strategies and keys to be applied to each situation,
      in the contents of the messages to be communicated and in the attitudes of
      professionals.

PMID- 22374771
TI  - [Autism and neural connectivity].
AB  - INTRODUCTION: Recent studies have investigated functional and structural brain
      connectivity in patients with autism spectrum disorders (ASD). Neuroimaging and
      electroencephalographic studies have found evidences suggesting that connectivity
      patterns are altered in ASD. AIMS: To review recent works from structural and
      functional neuroimaging and neurophysiological studies, and to provide a summary
      of advances in research implicating disordered connectivity in ASD. DEVELOPMENT:
      Functional findings reveal that patients with ASD have deficit in long-distance
      connections (under-connectivity), with a most prominent deficit in fronto
      posterior connections. With regard to structural connectivity there is evidence
      of disruption to inter-hemispheric white matter structures. Less functional
      studies reveal that patients with ASD also have an excess of local connections
      (over-connectivity), but findings from structural studies are considerably more
      inconsistent. CONCLUSIONS: The converging findings of functional connectivity
      abnormalities and white matter abnormalities in autism suggest that alterations
      in neural connectivity and the communication between different brain regions may
      be involved in behavioral and cognitive deficits associated with autism.

PMID- 22374772
TI  - [Abnormalities of synaptogenesis in autism. Pathogenic and therapeutic
      implications].
AB  - INTRODUCTION: The social, language, and behavioural problems that occur with
      autism suggest that this syndrome affects a functionally diverse and widely
      distributed set of neural systems. AIMS: To review the molecular pathways
      involved in synaptic growth, development, and stability of human synapses. We
      also examine the genes implicated in synaptogenesis which have been associated
      with autism. In particular, we highlight the role of these genes in synaptic cell
      adhesion, organization of presynaptic and postsynaptic specializations, growth
      signaling pathways, and endosomal function. DEVELOPMENT: Proper brain function
      requires stringent balance of excitatory and inhibitory synapse formation during
      neural circuit assembly. Mutation of genes that normally sculpt and maintain this
      balance results in severe dysfunction, causing neurodevelopmental disorders
      including autism, epilepsy, Angelman syndrome, fragile X syndrome, and Rett
      syndrome. Such mutations may result in defective architectural structuring of
      synaptic connections, molecular assembly of synapses and/or functional
      synaptogenesis. CONCLUSIONS: Increased knowledge of abnormal mechanisms of human
      synaptogenesis may lead to define different etio-pathogenic models of autism and
      to understand how far abnormal cell/synaptic growth and synaptic function could
      be reversed.

PMID- 22374773
TI  - [Differential diagnosis between the autistic spectrum and the schizophrenic
      spectrum].
AB  - INTRODUCTION: The nosological distinction between the autistic spectrum and the
      schizophrenic spectrum is clearly defined today, despite scientific evidence of
      the genetic relationship between the two conditions. The overlap between the
      negative symptoms of schizophrenia and certain autistic manifestations, and the
      fact that professionals who are not familiar with autistic spectrum disorders
      have misguidedly attributed positive symptoms of schizophrenia in autism together
      highlight the importance of deciphering the keys that make it possible to reach a
      differential diagnosis or to evaluate the comorbidity and co-occurrence of both
      spectra when this is the case. DEVELOPMENT: The article analyses and unravels the
      manifestations of autism that could be mistaken for the psychotic dimension and
      the disorganisation dimension corresponding to the positive symptoms of the
      schizophrenic spectrum. It also seeks to clarify the psychological explanations
      justifying the manifestation of certain negative symptoms frequently associated
      with autism. CONCLUSIONS: The keys to determining whether the clinical
      manifestations belong to the autistic spectrum, the schizophrenic spectrum or
      result from comorbidity lie in the evaluation of the developmental history of the
      person, the prodrome and onset of the condition, its course and the presence or
      absence of positive symptoms of schizophrenia. Determining them will play a
      crucial role in helping the professional to make decisions concerning both the
      diagnosis and treatment.

PMID- 22374774
TI  - [Comprehensive models of treatment in individuals with autism spectrum
      disorders].
AB  - INTRODUCTION. The steady increase in the number of children with autism spectrum
      disorders, has led to a better social awareness but also to a higher demand for
      specific interventions. This has questioned what the most appropriate and
      effective procedures for detection, diagnosis and treatment are. AIM. To review
      different approaches and classifications of interventions with individuals with
      autism spectrum disorders based on scientific evidence. DEVELOPMENT. According to
      the latest revisions, there are three types of classifications to categorize
      evidence-based interventions: practice-based intervention, comprehensive models
      of treatment and drug treatments. There are difficulties in comparing results of
      different methods of intervention, however, some common elements to prove their
      effectiveness have been identified. CONCLUSIONS. All intervention models should
      include functional communication skills, meaningful learning, carried out in
      various contexts, addressing challenging behaviors through positive behavioral
      support, promoting activities with peers and emphasize the role of parents in the
      planning and implementation of the objectives.

PMID- 22374775
TI  - [Measurements of stress and family impact in the parents of children with autism
      spectrum disorders before and after taking part in a training programme].
AB  - INTRODUCTION: The presence of a child with autism spectrum disorder (ASD) in the
      family causes an overall impact on parents and siblings manifested in a
      significant increase in stress. AIM: To analyze whether the implementation of a
      specific school of families for parents of people with ASD has a positive effect
      in the family impact, specifically in the stress perception and skills of parents
      who have children with ASD. SUBJECTS AND METHODS: A total of 27 parents having
      children with ASD participated in a school of families from which 13 of them
      filled a questionnaire of family impact before and after attending the training.
      Frequency and comparison analysis were carried out through the Wilcoxon interval
      test. RESULTS: After the following of the school of families, improvement
      tendencies were shown regarding the decrease of parent's stress, as regards the
      perception about their answers on their son's behaviors, and significantly, in
      the assessment of the quality of the time shared among parents and typically
      developing siblings. CONCLUSIONS: It is necessary to implement research programs
      with bigger samples aimed at being more precise on the influence of the specific
      training in stress for parents. The idea of developing training programs for
      families with ASD children is recommended for the different services that support
      this population as a way of helping in the decrease of stress.

PMID- 22374776
TI  - [Genomic endophenotypes of attention deficit hyperactivity disorder].
AB  - Attention deficit hyperactivity disorder (ADHD) is a remarkably heterogeneous
      neurobiological disorder. This characteristic is aetiologically mediated by
      genetic and environmental factors. Numerous studies have shown that different
      genes play a moderate but complex role in the aetiology of ADHD. Significant
      associations have been identified with several candidate genes for this disorder,
      including DAT1, DRD4, DRD5, 5HTT, HTR1B or SNAP25. The neurocognitive models of
      ADHD have been largely based on the findings from neuroimaging studies conducted
      in patients with ADHD, when establishing hypotheses capable of explaining the
      clinical features that are observed. From a neurobiological point of view, the
      genetic architecture of these patients or the interaction of the above-mentioned
      genes should at least partially account for the neuroanatomical and
      neuropsychological findings observed, which explains the axiomatic antithesis in
      the title. Nevertheless, the results of studies into the relationship between the
      genotyping and the neuroimaging or psychological findings are scarce and
      contradictory. The methodological differences in the volumetric analyses, the
      sizes of the populations studied, the neuropsychological batteries that are used,
      the presence of previous pharmacological treatment or comorbidity could account
      for these results.

PMID- 22374777
TI  - [Attention deficit hyperactivity disorder and epilepsy in childhood].
AB  - INTRODUCTION: Both attention deficit hyperactivity disorder (ADHD) and epilepsy
      are common disorders in childhood. ADHD and epilepsy can be detrimental to the
      behavior, learning and social relations of affected children. Children with
      epilepsy and ADHD tend to be at higher risk of school difficulties compared with
      children who suffer from epilepsy only. DEVELOPMENT: We review the works on the
      prevalence of ADHD in the epileptic population, the prevalence of epilepsy in
      children with ADHD, and electroencephalographic abnormalities observed in
      patients with ADHD. CONCLUSION: The prevalence of ADHD in childhood epilepsy is
      higher than in the general population and as is the rate of epilepsy in ADHD.
      Further studies are required to assess the bidirectional relationship between
      ADHD and epilepsy and the impact of electroencephalographic abnormalities in the
      clinical course of these patients.

PMID- 22374778
TI  - [Cognitive evoked potentials and executive functions in children with attention
      deficit hyperactivity disorder].
AB  - INTRODUCTION: Cognitive evoked potentials (P300) have been core of interest in
      attention deficit hyperactivity disorder (ADHD) research. The identification of
      its relationship with the most ecological aspects of executive dysfunction
      involves a link between neurophysiological and functional frames for a better
      treatment approach and monitoring of the evolution of the disorder. AIMS: To
      explore the differences in latency and amplitude of P300 component in Cz, Fz and
      Pz, between ADHD and no-ADHD children, and to analyze the correlations between
      variables of P300 and indexes of a measurement of executive functioning at home.
      SUBJECTS AND METHODS: Two groups were performed: an ADHD group of 16 children
      with a diagnosis of combined ADHD; and a group of 8 children without ADHD.
      Cognitive event-related potentials (P300) were registered and analyzed in an
      auditory and a visual modality. In addition, fathers fulfilled an executive
      behavior scale -Behavior Rating Inventory for Executive Function (BRIEF)-.
      RESULTS. The differences between the ADHD and the control group were significant,
      in visual and auditory latencies and in visual amplitudes. Significant
      correlations were found between some variables of P300 component and the BRIEF
      subscales. CONCLUSION: These results remark the utility of cognitive evoked
      potentials for the executive dysfunction in ADHD research, and emphasize the
      necessity of keeping the clinical assessment in diagnosis and monitoring of these
      children.

PMID- 22374779
TI  - Carbon(sp(3))-fluorine bond-forming reductive elimination from palladium(IV)
      complexes.
AB  - Pd(IV)-fluoride complexes, some of which are remarkably insensitive to water,
      have been synthesized and used in the title reaction, which proceeds with high
      selectivity to give the product of the C(sp(3))-F coupling. Preliminary
      mechanistic studies implicate a pathway involving dissociation of pyridine
      followed by direct C-F coupling at the Pd center.

PMID- 22374780
TI  - Tracheal reconstruction with a modified infrahyoid myocutaneous flap.
AB  - Reconstruction of a tracheal defect is a challenge because it often requires
      invasive surgery associated with relatively high morbidity. We recently invented
      a less-invasive method using a modified infrahyoid myocutaneous (IHMC) flap for
      the reconstruction of a tracheal defect in an 83-year-old male. A tracheal
      defect, the right half of the cricoid cartilage plus the right three quarters of
      the I-IV tracheal cartilage (about 3 * 4 cm), was reconstructed with a modified
      IHMC flap composed of the sternohyoid and platysma muscles and a skin pedicle.
      Considering the age of patient, we avoided rigid reconstruction and used a soft
      silicone tracheal opening retainer (Koken Co., Ltd., Tokyo, Japan) as an anterior
      wall dilator after surgery and waited for the scarring of the flap until it
      become rigid enough. The postoperative course was uneventful and the trachea was
      reconstructed safely. Tracheal reconstruction with an IHMC flap is a useful and
      less-invasive alternative compared to end-to-end anastomosis or reconstruction
      with a forearm flap, which is currently used as a mainstay.

PMID- 22374781
TI  - A fluorogenic reactive monolayer platform for the signaled immobilization of
      thiols.

PMID- 22374782
TI  - Correlation imaging for multiscan MRI with parallel data acquisition.
AB  - A new approach to high-speed magnetic resonance imaging (MRI) that uses all the
      data acquired in a multiscan imaging session is presented. This approach
      accelerates MRI data acquisition by statistically estimating correlation
      functions from images with different contrast and/or resolution. In multiscan MRI
      with parallel data acquisition, the estimation of correlation functions is
      dynamically improved as imaging proceeds. This allows imaging acceleration
      factors to be increased in subsequent scans, thereby reducing the total time of a
      multiscan MRI protocol. Furthermore, the correlation function estimates bring
      information about both coil sensitivity and anatomical structure into image
      reconstruction, thereby offering the ability to speed up MRI beyond the parallel
      imaging acceleration limit posed by a coil array alone. In this study, the
      feasibility of correlation imaging is demonstrated experimentally using brain and
      spine imaging protocols. The ability of correlation imaging to achieve an
      aggregate acceleration factor in excess of the number of coil elements in the
      phase encoding direction is also demonstrated.

PMID- 22374784
TI  - Detection of EPO doping and blood doping: the haematological module of the
      Athlete Biological Passport.
AB  - The increase of the body's capacity to transport oxygen is a prime target for
      doping athletes in all endurance sports. For this pupose, blood transfusions or
      erythropoiesis stimulating agents (ESA), such as erythropoietin, NESP, and CERA
      are used. As direct detection of such manipulations is difficult, biomarkers that
      are connected to the haematopoietic system (haemoglobin concentration,
      reticulocytes) are monitored over time (Athlete Biological Passport (ABP)) and
      analyzed using mathematical models to identify patterns suspicious of doping.
      With this information, athletes can either be sanctioned directly based on their
      profile or targeted with conventional doping tests. Key issues for the
      appropriate use of the ABP are correct targeting and use of all available
      information (e.g. whereabouts, cross sectional population data) in a forensic
      manner. Future developments of the passport include the correction of all
      concentration-based variables for shifts in plasma volume, which might
      considerably increase sensitivity. New passport markers from the genomic,
      proteomic, and metabolomic level might add further information, but need to be
      validated before integration into the passport procedure. A first assessment of
      blood data of federations that have implemented the passport show encouraging
      signs of a decreased blood-doping prevalence in their athletes, which adds
      scientific credibility to this innovative concept in the fight against ESA- and
      blood doping.

PMID- 22374783
TI  - miRNAs expressed differently in cancer stem cells and cancer cells of human
      gastric cancer cell line MKN-45.
AB  - Recent studies show that cancers may originate from special cells named cancer
      stem cells (CSCs). As miRNAs have a prominent role in regulating cell activities,
      a question arise, that is, if there is any difference in miRNA expression level
      between CSC and other cancer cells of human gastric cancer cell line MKN-45. In
      this study, CSCs were isolated by fluorescence-activated cell sorter based on the
      expression level of cell surface marker CD44. CSC characteristics were checked
      using spheroid formation assay and soft agar assay. Using reverse transcriptase
      polymerase chain reaction (RT-PCR), the expression level of some stemness genes
      was studied. Real-time q-PCR was used for analysis of the expression level of
      miRNAs. CSCs were able to make spheroids and colonies, whereas other cancer cells
      failed to show aforementioned features. In addition, RT-PCR resulted in a
      difference in the expression levels of Nanog, Sox2, Lin28 and Oct-4 between these
      two kinds of cells. Real-time RT-PCR analysis demonstrated an increase in mir-21
      and mir-302 expression level in CSCs, relative to cancer cells, whereas let-7a
      expression level was decreased in CSC in comparison with cancer cells, which may
      be due to their different differentiation level. On the other hand, mir-372, mir
      373 and mir-520c-5p were markedly increased in cancer cells in comparison with
      CSCs. This study shows that there is a difference in miRNA expression level
      between CSCs and other cancer cells, which reflects dissimilar molecular pathways
      in these cells. These miRNAs may be promising objects for targeting CSCs
      specifically and efficiently.

PMID- 22374785
TI  - The arduous journey to find a portrait of Beauchene fils: a famous anatomist and
      surgeon.
AB  - Earlier publications by our group have reported the major contributions of
      Beauchene fils, Edme Francois Chauvot de Beauchene (1778-1830), a prosector, and
      surgeon in Paris. These included a variety of firsts: the finding of an
      intraneural ganglion cyst, the description of the exploded skull (Beauchene)
      technique, and the case of air pulmonary embolism. This article describes the
      exhaustive efforts necessary to locate a portrait of him. Information obtained
      along the circuitous journey through 13 generations over five centuries will
      clarify the important medical accomplishments by individuals of a noble family.
      The discovered portraits will allow scholars to honor accurately the individuals,
      particularly Beauchene fils, in the future.

PMID- 22374786
TI  - Frequent activating GNAS mutations in villous adenoma of the colorectum.
AB  - To elucidate the role of GNAS mutations in colorectal tumourigenesis, we
      performed a mutation analysis in a total of 234 colorectal tumours, including
      adenomas, serrated lesions and adenocarcinomas. Activating GNAS mutations were
      found in 20 of the 24 villous adenomas (83%) but were absent in all the other
      tumours, except for one tubulovillous adenoma (3%) and two adenocarcinomas (3%).
      KRAS and BRAF mutations were always mutually exclusive. KRAS mutations were
      frequent in villous (67%) and tubulovillous (60%) adenomas but were rare or
      absent in tubular adenomas (6%) and serrated lesions, including hyperplastic
      polyps, sessile serrated polyps/sessile serrated lesions and traditional serrated
      adenomas (0-9%). BRAF mutations were found in four villous adenomas (17%) and in
      the large majority of serrated lesions (81-92%), but were absent in tubular and
      tubulovillous adenomas. Seventeen villous adenomas (71%) harboured GNAS mutations
      concomitantly with KRAS or BRAF mutations. Immunohistochemically, all the villous
      adenomas retained mismatch repair protein expression, suggesting that they are
      microsatellite-stable. The current study showed that the presence of activating
      GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic
      genetic feature of colorectal villous adenoma.

PMID- 22374787
TI  - Reconstruction of cell lineage and spatiotemporal pattern formation of the
      mesoderm in the amphipod crustacean Orchestia cavimana.
AB  - BACKGROUND: Cell lineage studies in amphipods have revealed an early restriction
      of blastomere fate. The mesendodermal cell lineage is specified with the third
      cleavage of the egg. We took advantage of this stereotyped mode of development by
      fluorescently labeling the mesodermal precursors in embryos of Orchestia cavimana
      and followed the morphogenesis of the mesodermal cell layer through embryonic
      development. RESULTS: The mesoderm of the trunk segments is formed by a very
      regular and stereotypic cell division pattern of the mesoteloblasts and their
      segmental daughters. The head mesoderm in contrast is generated by cell movements
      and divisions out of a mesendodermal cell mass. Our reconstructions reveal the
      presence of three different domains within the trunk mesoderm of the later
      embryo. We distinguish a cell group median to the limbs, a major central
      population from which the limb mesoderm arises and a dorsolateral branch of
      mesodermal cells. CONCLUSIONS: Our detailed description of mesodermal development
      relates different precursor cell groups to distinct muscle groups of the embryo.
      A dorsoventral subdivision of mesoderm is prepatterned within the longitudinal
      mesodermal columns of the germ-band stage. This makes amphipods excellent
      crustacean models for studying mesodermal differentiation on a cellular and
      molecular level.

PMID- 22374789
TI  - Assessments and admissions during the first 6 years of a UK medium secure DSPD
      service.
AB  - BACKGROUND: Offenders with personality disorder represent a considerable burden
      on mental health and criminal justice services. Millfields Unit was one of the
      pilot medium secure units (MSUs) established by the UK Department of Health and
      Ministry of Justice to provide dedicated services for such individuals. AIMS: Our
      study aimed to describe a complete cohort of referrals made to the service and to
      explore decisions on admissions to the Unit. METHODS: File review was used to
      collect a structured data set of information on the first 158 referrals. These
      were then analysed descriptively and inferentially. RESULTS: Previous
      psychological treatment in prison and evidence of motivation for further
      treatment were the strongest predictors of admission to the service. People
      admitted showed evidence of more extensive criminal histories, prior treatment
      failure and higher level of risk than those accepted into conventional medium
      secure units. Despite the stated purpose of the units being for people with
      personality disorder, a high number of patients with a primary diagnosis of
      psychotic illness were referred. CONCLUSION: The new service accepted a high-risk
      group of people with personality disorder whose needs would not otherwise have
      been met.

PMID- 22374790
TI  - Chemical bonding and atomic structure in Y2O3:ZrO2-SrTiO3 layered
      heterostructures.
AB  - Repeating boundaries: the buried interfaces in artificial heterostructures
      produced by sequential deposition of nanosized units are critical to their
      properties. With density functional theory it was shown that in Y(2)O(3):ZrO(2)
      (YSZ) and SrTiO(3) (STO) heterostructures reconstruction of the interfaces
      between the component units is required to access the most favorable structure.

PMID- 22374788
TI  - Differential effects of substrate modulus on human vascular endothelial, smooth
      muscle, and fibroblastic cells.
AB  - Regenerative medicine approaches offer attractive alternatives to standard
      vascular reconstruction; however, the biomaterials to be used must have optimal
      biochemical and mechanical properties. To evaluate the effects of biomaterial
      properties on vascular cells, heparinized poly(ethylene glycol) (PEG)-based
      hydrogels of three different moduli, 13.7, 5.2, and 0.3 kPa, containing
      fibronectin and growth factor were utilized to support the growth of three human
      vascular cell types. The cell types exhibited differences in attachment,
      proliferation, and gene expression profiles associated with the hydrogel modulus.
      Human vascular smooth muscle cells demonstrated preferential attachment on the
      highest-modulus hydrogel, adventitial fibroblasts demonstrated preferential
      growth on the highest-modulus hydrogel, and human umbilical vein endothelial
      cells demonstrated preferential growth on the lowest-modulus hydrogel
      investigated. Our studies suggest that the growth of multiple vascular cell types
      can be supported by PEG hydrogels and that different populations can be
      controlled by altering the mechanical properties of biomaterials.

PMID- 22374793
TI  - Late complications of nickel-titanium alloy stent in tracheal stenosis.
AB  - OBJECTIVES/HYPOTHESIS: To investigate and treat the late complications of using
      nickel-titanium alloy stents in laryngotracheal, bronchial, and esophageal
      stenosis patients who developed severe laryngotracheal stenosis (SLS). STUDY
      DESIGN: Retrospective clinical study. METHODS: Thirteen patients with SLS or
      tracheoesophageal fistula secondary to insertion of a nickel-titanium alloy stent
      for treatment of laryngotracheal, bronchial, or esophageal stenosis treated
      between May 2004 and March 2010 were retrospectively analyzed. Of the 13 total
      patients, nine had one stent placed, and four had two stents placed. The late
      complications observed were glottic and/or subglottic extension of cervical
      tracheal stenosis (n = 6), new stricture of the thoracic trachea (n = 4), severe
      left bronchial stricture with massive left pulmonary collapse (n = 1), and
      cervical tracheoesophageal fistula (n = 2). RESULTS: Six patients with glottic
      and/or subglottic to cervical tracheal stenosis underwent successful
      laryngotracheal reconstruction. Two patients with subglottic and upper thoracic
      tracheal stenosis were successfully treated by staged operation for the stenosis.
      Two patients with subglottic and distal thoracic tracheal stenosis are still
      undergoing treatment. One patient with severe left bronchial stricture and
      massive left pulmonary collapse has been treated but has not achieved full
      recovery. One patient with cervical tracheoesophageal fistula underwent
      successful repair but died later from metastatic disease. One patient with
      tracheoesophageal fistula died from massive hemorrhage and asphyxiation induced
      by the stent, which had not been removed. CONCLUSIONS: The nickel-titanium alloy
      stents should be used with extreme caution in patients with laryngotracheal,
      bronchial, or esophageal stenosis treatment that can be corrected by surgical
      therapy.

PMID- 22374794
TI  - Examination of the kinetic isotopic effect to the acetylation derivatization for
      the gas chromatographic-combustion-isotope ratio mass spectrometric doping
      control analysis of endogenous steroids.
AB  - In gas chromatographic-combustion-isotope ratio mass spectrometry (GC-C-IRMS)
      doping control analysis, endogenous androgenic anabolic steroids and their
      metabolites are commonly acetylated using acetic anhydride reagent, thus
      incorporating exogenous carbon that contributes to the measured isotope ratio.
      Comparison of the endogenous delta(13)C of free, mono-, and di-acetylated
      steroids requires application of corrections, typically through straightforward
      use of the mass balance equation. Variability in kinetic isotope effects (KIE)
      due to steroid structures could cause fractionation of endogenous steroid carbon,
      resulting in inaccurate results. To test for possible KIE influence on
      delta(13)C, acetic anhydride of graded isotope ratio within the natural abundance
      range was used under normal derivatization conditions to test for linearity. In
      all cases, plots of measured steroid acetate delta(13)C versus acetic anhydride
      delta(13)C were linear and slopes were not significantly different. Regression
      analysis of the Deltadelta(13)C of enriched acetic anhydrides versus
      Deltadelta(13)C of derivatized steroids shows that KIE are similar in all cases.
      We conclude that delta(13)C calculated from the mass balance equation is
      independent of the delta(13)C of the acetic anhydride reagent, and that net KIE
      under normal derivatization conditions do not bias the final reported steroid
      delta(13)C.

PMID- 22374795
TI  - Human OCTN2 (SLC22A5) is down-regulated in virus- and nonvirus-mediated cancer.
AB  - The expression of carnitine plasma membrane transporter OCTN2 was evaluated in
      virus and nonvirus-mediated cancer. Both OCTN2 mRNA and protein levels were
      reduced in keratinocytes retrotransduced with HPV16 E6 and E7 compared with the
      control. The OCTN2 expression was reduced also in keratinocytes retrotransduced
      with the sole HPV16 E6. A similar down-regulation of OCTN2 mRNA level was
      observed in a naturally HPV16-infected cancer cell line, CaSki, harbouring
      several copies of HPV16 whole genome. The mechanism of down-regulation is not
      related to p53 transcriptional activity because in SAOS (p53-null) cell line, the
      restoration of p53 expression did not rescue OCTN2 expression. The treatment of
      keratinocytes retrotransduced with HPV16 E6 and E7 with 5-aza-cytidine rescued
      the OCTN2 expression, indicating that the mechanism of down-regulation is linked
      to DNA methylation. Low levels of mRNA expression of OCTN2 were found also in
      several nonvirus-related epithelial cancer cell lines. The treatment of those
      cell lines with 5-aza-cytidine again rescued the expression of OCTN2 as well.
      These data demonstrate for the first time that the OCTN2 transporter is generally
      down-regulated in virus and nonvirus-mediated epithelial cancers, probably via
      methylation of its promoter region.

PMID- 22374796
TI  - Verification of a standardized method for inserting intramuscular EMG electrodes
      into uniquely oriented segments of gluteus minimus and gluteus medius.
AB  - Guidelines for assessing the function of gluteus minimus and gluteus medius with
      electromyography (EMG) traditionally offer one electrode placement site per
      muscle. However, anatomical studies suggest that there are two uniquely oriented
      segments within gluteus minimus (anterior and posterior), and three within
      gluteus medius (anterior, middle, and posterior) with potential for independent
      function. Assessment of these muscles with one electrode may therefore provide
      only a limited account of their role. Thus, the aim of this cadaveric study was
      to verify guidelines for placing intramuscular electrodes into two uniquely
      oriented segments of gluteus minimus, and three segments of gluteus medius. The
      guidelines were developed with reference to anatomical reports, cadaveric
      observation and real-time ultrasound imaging in vivo. Five cadaveric gluteal
      regions were marked for intramuscular electrode insertions based on these
      guidelines. Intramuscular electrodes were inserted into the marked regions of
      gluteus minimus (2*) and gluteus medius (3*) with the aid of a 15 cm biopsy
      needle. Systematic dissection revealed that electrodes were successfully inserted
      into uniquely oriented segments of gluteus minimus and medius. The orientation of
      fascicles surrounding each electrode was also consistent with segmental
      descriptions in past anatomical research. The findings of this research suggest
      that the guidelines described may be used to assess the functional role of
      segments within gluteus minimus and medius in health and dysfunction using EMG.
      Finally, electromyographers intent on investigating the role of posterior gluteus
      minimus must be cautious of the superior gluteal neurovascular bundle.

PMID- 22374797
TI  - The morphology and stability of nanoscopic gas states at water/solid interfaces.
AB  - Nanoscale gas bubbles have surprising stability at water/solid surfaces. Herein,
      we summarize progress made on investigating gases at the water/solid interfaces
      on the nanometer scale. The gas states include nanobubbles, micropancakes,
      multiple gas layers and their coexistence; these were investigated from
      experimental and theoretical aspects. The stability of nanoscale gas bubbles may
      be attributed to high inner density, as observed in molecular dynamic simulations
      and theoretical analysis. Moreover, it was found that there were maximal length
      scales for stable nanobubbles, namely, 100 nm high and a curvature radius of 2
      MUm.

PMID- 22374798
TI  - Improved T2 mapping accuracy with dual-echo turbo spin echo: effect of phase
      encoding profile orders.
AB  - Turbo spin echo (TSE) pulse sequences have been applied to estimate T(2)
      relaxation times in clinically feasible scan times. However, T(2) estimations
      using TSE pulse sequences has been shown to differ considerable from reference
      standard sequences due to several sources of error. The purpose of this work was
      to apply voxel-sensitivity formalism to correct for one such source of error
      introduced by differing phase encoding profile orders with dual-echo TSE pulse
      sequences. The American College of Radiology phantom and the brains of two
      healthy volunteers were imaged using dual-echo TSE as well as 32-echo spin-echo
      acquisitions and T(2) estimations from uncorrected and voxel-sensitivity
      formalism-corrected dual-echo TSE and 32-echo acquisitions were compared. In all
      regions of the brain and the majority of the analyses of the American College of
      Radiology phantom, voxel-sensitivity formalism correction resulted in
      considerable improvements in dual-echo TSE T(2) estimation compared with the 32
      echo acquisition, with improvements in T(2) value accuracy ranging from 5.2% to
      18.6%.

PMID- 22374799
TI  - Bone mineral as an electrical energy reservoir.
AB  - Mechanical stress in bone induces an electrical potential generated by
      piezoelectricity arising from displacement of collagen fibrils. Where and for how
      long the potential is stored in bone; however, are still poorly understood. We
      investigated the electrical properties of collagen fibrils and apatite minerals
      and found that bone, when polarized electrically by applying an external voltage,
      depolarizes by two mechanisms. Plots of thermally stimulated depolarization
      current show two significant peaks: one at 100 degrees C, attributed to collagen
      fibrils because decalcified bone exhibits depolarization peak at 100 degrees C,
      and the other at 500 degrees C, attributed to apatite minerals because calcined
      bone exhibits depolarization peak at 500 degrees C and has activation energy
      similar to that for synthesized apatite. The crystallographic c-axis orientation
      of calcined bone depends on the direction in which the bone is cut, either
      transverse or longitudinal, and strongly affects the polarization efficacy.

PMID- 22374800
TI  - Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a
      zebrafish xenograft model.
AB  - Inhibition of VEGF signalling effectively suppresses localized tumour growth but
      accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To
      study the dynamic and reciprocal interactions between tumour cells and their
      microenvironment during these processes, we established a xenograft model by
      injecting tumour cells into the blood circulation of transparent zebrafish
      embryos. This reproducibly results in rapid simultaneous formation of a localized
      tumour and experimental micrometastasis, allowing time-resolved imaging of both
      processes at single-cell resolution within 1 week. The tumour vasculature was
      initiated de novo by remodelling of primitive endothelial cells into a functional
      network. Roles of myeloid cells in critical tumourigenesis steps such as
      vascularization and invasion were revealed by genetic and pharmaceutical
      approaches. We discovered that the physiological migration of neutrophils
      controlled tumour invasion by conditioning the collagen matrix and forming the
      metastatic niche, as detected by two-photon confocal microscopy and second
      harmonic generation. Administration of VEGFR inhibitors blocked tumour
      vascularization and a localized tumour growth but enhanced migration of
      neutrophils, which in turn promoted tumour invasion and formation of
      micrometastasis. This demonstrates the in vivo cooperation between VEGF
      signalling and myeloid cells in metastasis and provides a new mechanism
      underlying the recent findings that VEGFR targeting can promote tumour
      invasiveness.

PMID- 22374801
TI  - Service user involvement in risk assessment and management: the Transition
      Inventory.
AB  - BACKGROUND: Drawing on self-prediction theory and the positive benefits of
      increasing health service user participation in risk assessments, the Transition
      Inventory (TI) was developed. It is an aid to the assessment of areas that people
      anticipate will be of difficulty in the next stage of transition, for example
      from open hospital to the community. AIMS: The aim of this paper is to determine
      reliability and convergent/discriminant validity data for the TI and its
      subscales, including behavioral impulsivity, social pressure, substance misuse,
      financial/employment, leisure, negative affect, interpersonal and family concerns
      and social alienation. METHODS: Eighty-eight male offenders coming towards the
      end of a period of imprisonment were asked to complete the TI. Their results were
      compared with the staff-rated Measures of Criminal Attitudes and Associates
      (MCAA) scale, alcohol blame and causation of crime items. Comparisons with the
      MCAA's antisocial intent scale, which is a future-orientated scale, and the
      associates scale allowed for convergent/discriminant validity to be examined with
      TI scales. With a community offender sample, TI results were used to predict
      researcher ratings. RESULTS: The TI scales demonstrated adequate internal
      consistency. Overall, the MCAA's antisocial intent scale had higher correlations
      with the TI than with a nonfuture-orientated scale. TI scales also demonstrated
      convergent validity with other measures and preliminary predictive validity with
      researcher ratings. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The TI provides a way
      to increase service user involvement in the assessments that determine when and
      how they transfer to settings where they will have more independence.

PMID- 22374802
TI  - Discovery of macrocyclic peptides armed with a mechanism-based warhead: isoform
      selective inhibition of human deacetylase SIRT2.
AB  - Designed to inhibit: by using the random nonstandard peptide integrated discovery
      (RaPID) system, highly potent isoform-selective inhibitors can be identified from
      a library of nonstandard macrocyclic peptides. These inhibitors, which contain a
      mechanism-based warhead residue, are active against the human deacetylase SIRT2,
      with IC(50) values in the low nanomolar region.

PMID- 22374803
TI  - Pharyngeal pouch surgery: a combined open and endoscopic approach.
AB  - Pharyngeal pouches are common, particularly in the elderly population, in whom
      they can cause significant morbidity. The advanced age of many patients and
      existing comorbidities mean that in some cases neither open nor endoscopic pouch
      stapling is possible. We present a technique of combined open and endoscopic
      pharyngeal pouch surgery, which may be used when other therapeutic options are
      limited.

PMID- 22374804
TI  - B1-based specific energy absorption rate determination for nonquadrature
      radiofrequency excitation.
AB  - The current gold standard to estimate local and global specific energy absorption
      rate for MRI involves numerically modeling the patient and the transmit
      radiofrequency coil. Recently, a patient-individual method was presented, which
      estimated specific energy absorption rate from individually measured B(1) maps.
      This method, however, was restricted to quadrature volume coils due to
      difficulties distinguishing phase contributions from radiofrequency transmission
      and reception. In this study, a method separating these two phase contributions
      by comparing the electric conductivity reconstructed from different transmit
      channels of a parallel radiofrequency transmission system is presented. This
      enables specific energy absorption rate estimation not only for quadrature
      excitation but also for the nonquadrature excitation of the single elements of
      the transmit array. Though the contributions of the different phases are known,
      unknown magnetic field components and tissue boundary artifacts limit the
      technique. Nevertheless, the high agreement between simulated and experimental
      results found in this study is promising. B(1)-based specific energy absorption
      rate determination might become possible for arbitrary radiofrequency excitation
      on a patient-individual basis.

PMID- 22374805
TI  - The dark side of a success story: microRNAs of the C19MC cluster in human
      tumours.
AB  - MicroRNAs are a class of macromolecules of rapidly emerging significance for the
      pathogenesis of numerous human diseases, including cancer. Moreover, many of them
      hold great promise as valid biomarkers because of their high extracellular
      stability. Chromosome 19 harbours the largest cluster of microRNA genes known so
      far, which has developed in a very short time during mammalian evolution. Thus,
      in terms of evolution, gain of this cluster is an apparent success story.
      Nevertheless, we know very little about how functions of its microRNAs have
      contributed to this success and apparently, at least some of them can turn from
      Jekyll into Hyde and contribute to tumourigenesis. Recent work published in the
      Journal of Pathology by Fornari and colleagues, addressed here, reveals how
      members of that cluster are involved in the molecular pathogenesis of
      hepatocellular carcinomas.

PMID- 22374806
TI  - Density, thermal expansion and viscosity of cholinium-derived ionic liquids.
AB  - Density and viscosity data of the N-alkyl-N,N-dimethyl-N-(2-hydroxyethyl)ammonium
      bis(trifluoromethylsulfonyl)imide ionic liquids homologous series [N(1 1 n
      2(OH))][Ntf(2)] with n=1, 2, 3, 4 and 5 have been measured at atmospheric
      pressure in the 283<T/K<373 temperature range and the corresponding isobaric
      thermal expansion coefficients have been calculated. This work studies the effect
      of increasing the alkyl chain length of the cholinium-based cation on the
      density, viscosity and related properties of this family of ionic liquids. A
      volumetric predictive method based on the effective molar volume of cations and
      anions is used to estimate the effective molar volume of the different cations
      present in this study. The results agree with data for other cation families that
      show a molar volume increment per CH(2) group on the alkyl chain of the cation of
      about 17.2 cm(3) mol(-1), except for [N(1 1 1 2(OH))](+), which exhibits an
      outlier behaviour. Molecular dynamics simulation results are used to explain the
      volumetric behaviour along the homologous series from a molecular perspective.
      The predictive power of group contribution methods for density and viscosity is
      also tested.

PMID- 22374807
TI  - Zwitterionic polycarboxybetaine coating functionalized with REDV peptide to
      improve selectivity for endothelial cells.
AB  - Surface immobilization of bioactive molecules has been a promising strategy to
      develop in situ endothelialization for cardiovascular implants. With the aim to
      construct endothelial cell specific coating with low fouling property,
      zwitterionic carboxybetaine methacrylate and butyl methacrylate were
      copolymerized as coating materials, spin-coated onto substrates, and immobilized
      with endothelial cell selective peptide Arg-Glu-Asp-Val (REDV) through
      functionalization of carboxy groups in carboxybetaine by NHS/EDC chemistry.
      Experimental results proved that carboxybetaine-REDV coating maintained desirable
      antifouling ability and fine hemocompatibility. Separate culture and coculture of
      HUVECs (human umbilical vein endothelial cells) with HUASMCs (human umbilical
      artery smooth muscle cells) showed that the coating was able to enhance the
      competitive growth of endothelial cells while limiting the adhesion,
      proliferation, and migration of smooth muscle cells. The existence of
      zwitterionic carboxybetaine helps to screen undesirable adsorption of platelets,
      and its nonspecific resistance to smooth muscle cells contributes to the
      realization of endothelial cell selectivity.

PMID- 22374808
TI  - Effect of rice parboiling on performance and metabolic responses in rats.
AB  - This research is aimed at evaluating the effect of rice grains submitted to
      different processing (white or parboiling) on performance and biological
      responses in rat. Male Wistar rats were fed with diets containing white or
      parboiled rice grains of the cultivar IRGA 417. Wet and dry faecal production,
      fasting serum glucose concentration, serum total protein and organs' weights as
      liver, kidney and epididymal fat pads were not affected by processing. The
      animals in the treatment with parboiled rice showed higher body weight gain, feed
      intake, nitrogen excretion, serum triglycerides, uric acid levels and pancreas
      weight and lower feed conversion, faecal pH, albumin and serum HDL cholesterol,
      when compared with the treatment with white rice. The results obtained in this
      work allow the conclusion that structural change of rice components caused by
      parboiling results in variations in different essential body metabolic
      parameters, such as body weight gain, gastrointestinal function and glycaemic
      control.

PMID- 22374809
TI  - The last step of kanamycin biosynthesis: unique deamination reaction catalyzed by
      the alpha-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH
      dependent reductase KanK.
AB  - Mystery solved: using heterologous expression, the activities of two enzymes
      exclusively belonging to the kanamycin biosynthetic pathway have been identified
      in vitro. A distinctive reaction mechanism to produce kanamycin is proposed and
      the previously unknown catalytic deamination activity of KanJ dioxygenase is
      uncovered.

PMID- 22374810
TI  - The synthesis and characterization N-methyl-3-phenyl-norbornan-2-amine
      (CamfetamineTM).
AB  - N-Methyl-3-phenyl-norbornan-2-amine (N-methyl-3-phenylbicyclo[2.2.1]heptan-2
      amine, Camfetamine(TM) ) is available from a number of online legal
      highs/research chemicals' vendors. Although it was developed as an analeptic by
      Merck in the early 1960s, it was never commercialized. However, the Association
      of Independent Research Chemical Retailers (AIRCR), an umbrella organization for
      a number of online vendors, has redeveloped it for use as a recreational drug. N
      Methyl-3-phenyl-norbornan-2-amine is closely related to fencamfamine which has
      been widely used as a central nervous system (CNS) stimulant and appetite
      suppressant. In this paper we describe the synthesis of N-methyl-3-phenyl
      norbornan-2-amine, its characterization and interpretations of its electron
      impact, and electrospray ionization mass spectra.

PMID- 22374811
TI  - Surgical anatomy of the superior gluteal nerve and landmarks for its localization
      during minimally invasive approaches to the hip.
AB  - The superior gluteal nerve (SGN) is vulnerable to damage during total hip
      arthroplasty and various pelvic surgeries. Recently introduced minimally invasive
      approaches to the hip show promise for less muscle trauma compared to
      conventional approaches. However, the risk of damaging the SGN has not been well
      documented for such alternative approaches. Therefore, we aimed to investigate
      the anatomic course of the SGN and to define anatomical landmarks that may be
      used by surgeons during minimally invasive approaches to the hip. Twenty-eight
      gluteal regions from 14 formalin-fixed cadavers were dissected and the course and
      the distances of the SGN and its branches to the tip of the greater trochanter
      (GT) were measured. The landmarks for standardizing the course of the SGN
      included the posterior inferior iliac spine (PIIS), GT, and a line (PIIS-GT)
      connecting these two points. The exit of the SGN was found to be at the medial
      one third of the PIIS-GT line and 5.4 cm from the GT. Two branching patterns were
      noted. The branches of the SGN were distributed lateral to the PIIS-GT line. On
      the basis of our study, the safe zone for the SGN was smaller than previously
      reported. Posterior, lateral, or anterolateral minimally invasive approaches to
      the hip should take into account the point of exit of the SGN and the area of
      distribution of its branches. A minimally invasive anterolateral approach may
      particularly compromise branches to the tensor fasciae latae muscle. Localization
      of the SGN and its branches using the anatomic landmarks defined in this study
      may decrease surgical morbidity.

PMID- 22374812
TI  - Abnormal gyration of the temporal lobe and megalencephaly are typical features of
      thanatophoric dysplasia and can be visualized prenatally by ultrasound.
AB  - Autopsies of fetuses with thanatophoric dysplasia (TD) have shown abnormal
      gyration of the temporal lobes. In addition, the head is relatively large
      compared with the abdomen. We evaluated by ultrasound six consecutive cases of TD
      at 19 + 0 to 19 + 6 gestational weeks based on last menstrual period. We observed
      abnormal and deep transverse sulci in the temporal lobes in all cases; these
      features were confirmed at autopsy. We performed biometric assessment, including
      biparietal diameter (BPD) and mean abdominal diameter (MAD). For each MAD value
      in the TD fetuses, we computed mean and SD of the corresponding BPD values from a
      population-based registry in the relevant age range, and used them to calculate Z
      scores for each BPD/MAD ratio. In the general population, the average BPD/MAD
      ratio was 1.05. In the TD fetuses, the mean BPD was 51.5 (range, 49-54) mm, the
      MAD was 45 (range, 41-47) mm and the BPD/MAD ratio was 1.15 (range, 1.09-1.20).
      The average Z-score of the ratios for TD fetuses was 2.44 (range, 1.05-3.39). The
      ratios for the TD fetuses were significantly higher than were the population
      ratios (P = 0.016). At autopsy, the mean brain-to-body weight ratio was 20.6%
      (range, 15.4-24.1%), which was greater than the corresponding mean ratio of 14.9%
      in normal fetuses. We conclude that abnormal and deep transverse gyration of the
      temporal lobes can be visualized by ultrasound in mid-second-trimester fetuses
      with TD. Due to megalencephaly, fetuses with TD have significantly different body
      proportions, with a larger BPD compared with normal fetuses.

PMID- 22374813
TI  - Cell motility of neural stem cells is reduced after SPIO-labeling, which is
      mitigated after exocytosis.
AB  - MRI is used for tracking of superparamagnetic iron oxide (SPIO)-labeled neural
      stem cells. Studies have shown that long-term MR tracking of rapidly dividing
      cells underestimates their migration distance. Time-lapse microscopy of random
      cellular motility and cell division was performed to evaluate the effects of SPIO
      labeling on neural stem cell migration. Labeled cells divided symmetrically and
      exhibited no changes in cell viability, proliferation, or apoptosis. However,
      SPIO-labeling resulted in decreased motility of neural stem cells as compared
      with unlabeled controls. When SPIO-labeled neural stem cells and human induced
      pluripotent stem cells were transplanted into mouse brain, rapid exocytosis of
      SPIO by live cells was observed as early as 48 h postengraftment, with SPIO
      depleted cells showing the farthest migration distance. As label dilution is
      negligible at this early time point, we conclude that MRI underestimation of cell
      migration can also occur as a result of reduced cell motility, which appears to
      be mitigated following SPIO exocytosis.

PMID- 22374814
TI  - Low-profile titanium mesh in the use of orbital reconstruction: A pilot study.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to share our clinical
      experience in the use and accuracy of a newly designed, low-profile titanium mesh
      (Modus OPS 1.5; Medartis, Basel, Switzerland) for primary internal orbital
      reconstruction. STUDY DESIGN: Observational study. METHODS: This study was
      conducted at the Department of Cranio-Maxillofacial Surgery at the University
      Hospital of Bern, Switzerland, starting November 2008. Patients were included who
      had a defect size of >=2 cm(2)  or fractures of more than one wall. The
      operations were performed within 14 days after trauma. To repair the orbital
      fracture, a newly designed titanium mesh was applied. The technical innovation in
      regard to these plates is the low-profile height of 0.25 mm along the border and
      0.2 mm in the mesh area. Two different sizes of two different types of mesh are
      available for reconstruction. Preoperative computed tomography (CT) scans were
      obtained to assess the fracture size and location. A maxillofacial surgeon
      performed pre- and postoperative assessments (at 2 weeks, 12 weeks, and 6
      months). Ophthalmologic assessments were performed preoperatively and 6 months
      after the operation. Postoperative CT scans were obtained within 12 weeks after
      the operation and the orbital volumes analyzed by a radiologist. RESULTS: Twenty
      seven patients underwent surgery (11 female; average age, 55.2 years). Final
      postoperative ophthalmologic follow-up was obtained at a mean of 8.8 months
      (range, 4.0-20.1 months). Twenty-five patients (93%) had a successful treatment
      outcome without complications. In two patients, the plate was buckled in the
      posterior edge region and had to be replaced. Surgical revision was performed
      within 3 weeks after the first procedure. These patients showed good clinical and
      radiologic outcome after the second procedure. At the final assessment, none of
      the patients had experienced diplopia. Three patients showed slight enophthalmos
      (2-mm side difference), however, without any subjective functional or aesthetic
      concerns. According to the literature, an average orbital volume difference of up
      to 1.95 cm(3)  is normal. In our study, radiologic volume assessment showed a
      side difference of >=2 cm(3)  in four patients, of which one patient presented
      with a clinically detectable enophthalmos. CONCLUSIONS: The newly designed, thin
      titanium mesh is a reliable and safe implant for the repair of orbital defects.
      Owing to insufficient intraoperative control, two plates showed buckling at the
      posterior border, which made a repair necessary. Awareness of this problem may
      avoid such complications in the future. However, it would seem reasonable to
      improve the stability of the mesh by increasing the profile height, to minimize
      potential complications.

PMID- 22374815
TI  - Activation of protein kinase Cdelta leads to increased pancreatic acinar cell
      dedifferentiation in the absence of MIST1.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis
      of < 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to
      develop PDAC, making it a significant risk factor for PDAC. While the
      relationship for the increased susceptibility to PDAC is unknown, loss of the
      acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can
      dedifferentiate or trans-differentiate into a number of cell types including duct
      cells, beta cells, hepatocytes and adipocytes. Knowledge of the molecular
      pathways that regulate this plasticity should provide insight into PDAC and CP.
      MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for
      complete acinar cell maturation. The goal of this study was to examine the
      plasticity of acinar cells that do not express MIST1 (Mist1(-/-) ). The fate of
      acinar cells from C57Bl6 or congenic Mist1(-/-) mice expressing an acinar
      specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice
      (Mist1(CreERT/-) R26r) was determined following culture in a three-dimensional
      collagen matrix. Mist1(CreERT/-) R26r acini showed increased acinar
      dedifferentiation, formation of ductal cysts and transient increases in PDX1
      expression compared to wild-type acinar cells. Other progenitor cell markers,
      including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1(-/-) cultures.
      Analysis of protein kinase C (PKC) isoforms by western blot and
      immunofluorescence identified increased PKCepsilon accumulation and nuclear
      localization of PKCdelta that correlated with increased duct formation. Treatment
      with rottlerin, a PKCdelta-specific inhibitor, but not the PKCepsilon-specific
      antagonist epsilonV1-2, reduced acinar dedifferentiation, progenitor gene
      expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue
      samples showed reduced MIST1 expression combined with increased nuclear PKCdelta
      accumulation. These results suggest that the loss of MIST1 is a common event
      during PDAC and CP and events that affect MIST1 function and expression may
      increase susceptibility to these pathologies.

PMID- 22374816
TI  - Endothelialization and in-stent restenosis on the surface of glycoprotein IIIa
      monoclonal antibody eluting stent.
AB  - Since the percutaneous transtuminal coronary angioplasty was introduced into
      China in 1984, this procedure has become widely accepted as an important step in
      coronary revascularization. This study shows the effect of the monoclonal
      antibody (mAb) on the platelet glycoprotein IIIa receptor during
      endothelialization and in-stent restenosis by implanting the mAb-eluting stents
      into iliac arteries of rabbits. The hard tissue cross sections of the stent
      implanted arterial segments were made by polymethylmethacrylate embedding.
      Arterial intima proliferation was observed and analyzed. The endothelialization
      of the stent surface was observed using scanning electron microscope, whereas the
      ultrastructure of the neointima was observed using transmission electron
      microscope. After one month of stent implantation, the surfaces of both groups
      were covered by intact endothelial layers, but the neointimal areas and the ratio
      of stenosis were significantly lesser in the mAb-eluting stent group (p < 0.01).
      After 3 months, the ratio of stenosis in the mAb-eluting stent group was 14.67 +/
      0.79, whereas that of the bare stent group was 21.58 +/- 1.76 (p < 0.01).
      Therefore, the mAb eluting from the stent surface has the potential to accelerate
      endothelialization, prevent thrombosis formation due to the interaction of stent
      with blood, and decrease the stenosis ratio by inhibiting neointima
      proliferation.

PMID- 22374817
TI  - Analysis of nascent rotational energy distributions and reaction mechanisms of
      the gas-phase radical-radical reaction O(3P)+(CH3)2CH->C3H6+OH.
AB  - This paper reports on the gas-phase radical-radical dynamics of the reaction of
      ground-state atomic oxygen [O((3)P), from the photodissociation of NO(2)] with
      secondary isopropyl radicals [(CH(3))(2)CH, from the supersonic flash pyrolysis
      of isopropyl bromide]. The major reaction channel, O((3)P)+(CH(3))(2)CH->C(3)H(6)
      (propene)+OH, is examined by high-resolution laser-induced fluorescence
      spectroscopy in crossed-beam configuration. Population analysis shows bimodal
      nascent rotational distributions of OH (X(2)Pi) products with low- and high-N''
      components in a ratio of 1.25:1. No significant spin-orbit or Lambda-doublet
      propensities are exhibited in the ground vibrational state. Ab initio
      computations at the CBS-QB3 theory level and comparison with prior theory show
      that the statistical method is not suitable for describing the main reaction
      channel at the molecular level. Two competing mechanisms are predicted to exist
      on the lowest doublet potential-energy surface: direct abstraction, giving the
      dominant low-N'' components, and formation of short-lived addition complexes that
      result in hot rotational distributions, giving the high-N'' components. The
      observed competing mechanisms contrast with previous bulk kinetic experiments
      conducted in a fast-flow system with photoionization mass spectrometry, which
      suggested a single abstraction pathway. In addition, comparison of the reactions
      of O((3)P) with primary and tertiary hydrocarbon radicals allows molecular-level
      discussion of the reactivity and mechanism of the title reaction.

PMID- 22374818
TI  - Improving bias and coverage in instrumental variable analysis with weak
      instruments for continuous and binary outcomes.
AB  - Causal estimates can be obtained by instrumental variable analysis using a two
      stage method. However, these can be biased when the instruments are weak. We
      introduce a Bayesian method, which adjusts for the first-stage residuals in the
      second-stage regression and has much improved bias and coverage properties. In
      the continuous outcome case, this adjustment reduces median bias from weak
      instruments to close to zero. In the binary outcome case, bias from weak
      instruments is reduced and the estimand is changed from a marginal population
      based effect to a conditional effect. The lack of distributional assumptions on
      the posterior distribution of the causal effect gives a better summary of
      uncertainty and more accurate coverage levels than methods that rely on the
      asymptotic distribution of the causal estimate. We discuss these properties in
      the context of Mendelian randomization.

PMID- 22374819
TI  - Fluorine in psychedelic phenethylamines.
AB  - The so-called psychedelic phenethylamines represent a class of drugs with a large
      range of psychoactive properties in humans, ranging from naturally occurring
      mescaline to amphetamine analogues and homologues. The interest in many of these
      compounds, occasionally referred to as designer-drugs, is widely dispersed across
      popular culture and political and scientific communities. In recent decades,
      fluorine has become a powerful and important tool in medicinal chemistry. In
      addition, fluorine-containing compounds and medicines can be found in numerous
      commercially successful pharmaceuticals that have gained a market share of some 5
      15%. One might anticipate this trend to increase in the future. As far as
      fluorinated phenethylamines are concerned, much less is known about their
      chemistry and pharmacology. This paper provides an overview regarding the
      biological properties of over 60 fluorinated phenethylamines and discusses both
      historical and recent chemistry-related developments. It was shown that the
      introduction of fluorine into the phenethylamine nucleus can impact greatly on
      psychoactivity of these compounds, ranging from marked loss to enhancement and
      prolongation of effects. For example, in contrast to the psychoactive escaline
      (70), it was observed that its fluoroescaline (76) counterpart was almost devoid
      of psychoactive effects. Difluoroescaline (77), on the other hand, retained, and
      trifluoroescaline (78) showed increased human potency of escaline (70).
      Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human
      potency and duration of mescaline (22) effects.

PMID- 22374820
TI  - A room-temperature X-ray-induced photochromic material for X-ray detection.
AB  - A color change: X-ray-induced photochromic species are rare and can be used for
      detection of X-rays. A highly robust X-ray-sensitive material with the discrete
      structure of a metal-organic complex has been found to show both soft and hard X
      ray-induced photochromism at room temperature. A new ligand-to-ligand electron
      transfer mechanism was proposed to elucidate this photochromic phenomenon.

PMID- 22374821
TI  - Recurrent prenatally diagnosed isolated bilateral pulmonary agenesis.

PMID- 22374822
TI  - Formation and decay of the dehydrogenated parent anion upon electron attachment
      to dialanine.
AB  - The dehydrogenated parent anion [M-H](-)  is one of the most dominant anions
      formed in dissociative electron attachment to various small biomolecules like
      nucleobases and single amino acids. In the present study, we investigate the [M
      H](-)  channel for the dipeptide dialanine by utilizing an electron monochromator
      and a two-sector-field mass spectrometer. At electron energies below 2 eV, the
      measured high-resolution ion-efficiency curve has a different shape to that for
      the single amino acid alanine, which is explained by the altered threshold
      energies for formation of [M-H](-)  determined in quantum chemical calculations.
      Moreover, the structure of the formed [M-H](-)  anion is further studied by
      investigating the unimolecular and collision-induced decay of this anion.
      Trajectory calculations have been carried out to aid the interpretation of the
      experimentally observed fragmentation patterns.

PMID- 22374823
TI  - Frontal sinus osteoma removal with the ultrasonic bone aspirator.
AB  - Osteomas, the most common skull tumors, are typically excised through either an
      open or endoscopic ostectomy using a high-speed drill, a technically challenging
      procedure that can result in injury to adjacent soft tissue structures. Osteoma
      removal through ultrasonic bone emulsification and aspiration (UBA) offers the
      advantages of decreased blood loss, preservation of adjacent soft tissue
      structures, and precise bone removal. UBA was used to successfully remove a
      forehead osteoma without injury to adjacent nerves and with a satisfactory
      cosmetic outcome. We describe skull osteoma removal with an ultrasonic bone
      aspirator, which offers potential advantages over conventional bone removal
      techniques.

PMID- 22374824
TI  - MR imaging near metal with undersampled 3D radial UTE-MAVRIC sequences.
AB  - Recently developed techniques such as the multiple acquisition with variable
      resonance image combination and slice encoding for metal artifact correction
      techniques have improved the ability of clinical magnetic resonance scanners to
      image near metal implants. These sequences are based on fast spin echo sequences
      which preclude detection of short T(2) tissues such as tendons, ligaments, and
      cortical bone. Ultrashort echo time sequences have the potential to detect
      signals from these tissues. In this study, we investigate the potential of
      combining ultrashort echo time with multiple acquisition with variable resonance
      image combination to image short T(2) musculoskeletal tissues adjacent to
      metallic implants. Different radio frequency excitation pulse types and spectral
      binning strategies were studied. We found that ultrashort echo time-multiple
      acquisition with variable resonance image combination sequences were able to
      significantly reduce typical artifacts near metal, as well as detect very short
      T(2) signals that are usually not visualized using clinical pulse sequences.

PMID- 22374825
TI  - An evaluation of the DRI-ETG EIA method for the determination of ethyl
      glucuronide concentrations in clinical and post-mortem urine.
AB  - A commercial enzyme immunoassay for the qualitative and semi-quantitative
      measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem
      (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902
      analyzer. The determined concentrations were compared with those obtained using a
      previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5
      ug/ml and LC-MS/MS limit of reporting of 0.1 ug/ml, there was a sensitivity of
      60.8% and a specificity of 100% for clinical samples. For post-mortem samples,
      sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the
      cut-off to 0.1 ug/ml, the sensitivity and specificity were 83.3% and 100% for
      clinical samples whereas for post-mortem samples the sensitivity and specificity
      were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and
      specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 ug/ml were achieved
      when using immunoassay cut-offs of 0.3 and 0.092 ug/ml, respectively. There was
      good correlation between quantitative results obtained by both methods but
      analysis of samples by LC-MS/MS gave higher concentrations than by enzyme
      immunoassay (EIA), with a statistically significant proportional bias (P<0.0001,
      Deming regression) for both sample types. The immunoassay is reliable for the
      qualitative and semi-quantitative presumptive detection of ethyl glucuronide in
      urine.

PMID- 22374826
TI  - Promoted healing of femoral defects with in situ grown fibrous composites of
      hydroxyapatite and poly(DL-lactide).
AB  - Although, electrospun composite fibers have shown promise in enhancing growth,
      differentiation, and mineralization of osteoblasts in vitro, bone repairing
      capabilities have not been clarified after in vivo implantation up to now. In
      situ grown composites (IGC) of hydroxyapatite (HA) and poly(DL-lactide) (PDLLA)
      were obtained from electrospun fibers grafted with gelatin as the induction sites
      for HA growth. The presence and location of HA nanoparticles within electrospun
      fibers were proposed to affect the degradation and repairing process of femoral
      defects. Subcutaneous implantation of IGC led to around 90% of mass loss and 75%
      of molecular weight reduction during 16 weeks, which were significantly higher
      than those after in vitro degradation in buffer solutions. In vitro tests on
      MC3T3-E1 cells indicated that IGC acted as a better cell support to provide
      favorable conditions for cell proliferation and to stimulate the osteogenic
      differentiation as compared with electrospun PDLLA fibers, and blend electrospun
      fibrous composites. Femoral defects were created for in vivo evaluation of bone
      repairing, indicating that the entire defect was filled by newly formed bone with
      compact structure after 16 week implantation of IGC. Histological and SEM
      observations demonstrated a successful bridging of the critical-sized defect with
      rapid mineralization, continual remodeling, and abundant vasculature. The in situ
      grown HA nanoparticles on the surface of electrospun fibers improved the
      biocompatibility with defect sites, promoted the bone formation within fibrous
      scaffolds and enhanced the bone remodeling, indicating potentials for bone
      regeneration and repairing of bone defects.

PMID- 22374827
TI  - Is short first-trimester crown-rump length associated with spontaneous preterm
      birth?
AB  - OBJECTIVE: To assess the association between first-trimester crown-rump length
      (CRL) and the risk of spontaneous preterm birth before 32 weeks' gestation.
      METHODS: We performed a matched case-control study of 129 women with spontaneous
      preterm birth at < 32 weeks' gestation (cases) and 129 women with term deliveries
      (controls) using data stored in the ultrasound and obstetric databases of our
      tertiary referral center. Cases and controls were individually matched based on
      maternal age, parity, history of preterm birth and medical indication for
      antenatal care. Fetal CRL measured between 8 + 0 and 13 + 6 weeks was expressed
      as multiples of the median (MoM) expected CRL, based on last menstrual period. We
      investigated the association between CRL-MoM and spontaneous preterm birth using
      logistic regression analysis. RESULTS: CRL-MoM was not associated with
      spontaneous preterm birth: odds ratio (OR) 1.10 (95% CI, 0.89-1.36) per 0.10 MoM
      increase in CRL. Timing of measurement did not influence the model (P = 0.59).
      This was confirmed when restricting the analysis to the 93 pairs with CRL
      measurements made between 10 + 0 and 13 + 6 weeks: OR for preterm birth 1.07 (95%
      CI, 0.83-1.37) per 0.10 MoM increase in CRL. CONCLUSION: A short CRL in the first
      trimester is not associated with spontaneous preterm birth before 32 weeks'
      gestation, thus short CRL cannot be used to identify women at increased risk of
      preterm birth.

PMID- 22374828
TI  - Mantle cell lymphoma displays a homogenous methylation profile: a comparative
      analysis with chronic lymphocytic leukemia.
AB  - Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature
      CD5(+) B-cell malignancies with different biological/clinical characteristics. We
      recently reported an association between different prognostic subgroups of CLL
      (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the
      relationship between DNA methylation and prognostic markers, such as the
      proliferation gene expression signature, has not been investigated in MCL. We
      applied high-resolution methylation microarrays (27,578 CpG sites) to assess the
      global DNA methylation profiles in 20 MCL (10 each with high/low proliferation
      signature) and 30 CLL (15 poor-prognostic IGHV unmutated subset #1 and 15 good
      prognostic IGHV mutated subset #4) samples. Notably, MCL and each CLL subset
      displayed distinct genomic methylation profiles. After unsupervised hierarchical
      clustering, 17/20 MCL cases formed a cluster separate from CLL, while CLL subsets
      #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes
      (n = 6) were identified between high vs. low proliferation MCL. In contrast,
      distinct methylation profiles were demonstrated for MCL and CLL. Importantly,
      certain functional classes of genes were preferentially methylated in either
      disease. For instance, developmental genes, in particular homeobox transcription
      factor genes (e.g., HLXB9, HOXA13), were more highly methylated in MCL, whereas
      apoptosis-related genes were enriched among targets methylated in CLL (e.g.,
      CYFIP2, NR4A1). Results were validated using pyrosequencing, RQ-PCR and
      reexpression of specific genes. In summary, the methylation profile of MCL was
      homogeneous and no correlation with the proliferation signature was observed.
      Compared to CLL, however, marked differences were discovered such as the
      preferential methylation of homeobox genes in MCL.

PMID- 22374829
TI  - STED microscopy and its applications: new insights into cellular processes on the
      nanoscale.
AB  - For about a decade, superresolution fluorescence microscopy has been advancing
      steadily, maturing from the proof-of-principle stage to routine application. Of
      the various techniques, STED (stimulated emission depletion) microscopy was the
      first to break the diffraction barrier. Today, it is a prominent and versatile
      form of superresolution light microscopy. STED microscopy has shed a sharper
      light on numerous topics in cell biology, but also in material sciences. Both
      disciplines extend into the nanometer range, making detailed studies of
      structural and functional relationships difficult or even impossible to achieve
      using diffraction-limited microscopy. With recent advancements like spectral
      multiplexing or live-cell imaging, STED microscopy makes nanoscale materials and
      components of the cell accessible for fluorescence-based investigations. With
      multicolor superresolution imaging, even the interactions between biological and
      engineered nanostructures can be studied in detail. This review gives an
      introduction into the working principle of STED microscopy, provides a detailed
      overview of recent advancements and new techniques implemented for use with STED
      microscopy and shows how these have been applied in the life sciences and
      nanotechnologies.

PMID- 22374830
TI  - Determination of the permeability characteristics of two sulfenamide prodrugs of
      linezolid across Caco-2 cells.
AB  - The purpose of this work was to study the permeability of two relatively
      lipophilic sulfenamide prodrugs of linezolid (clogP 0.85), N
      (phenylthio)linezolid (1, clogP 2.77) and N-[(2
      ethoxycarbonyl)ethylthio]linezolid (2, clogP 1.43), across Caco-2 cell
      monolayers. Both prodrugs were found to convert to linezolid in the donor
      compartment presumably from the reaction with free thiol groups on proteins on
      the surface of the Caco-2 cells, as no conversion was seen in the donor
      compartment media per se. Neither of the prodrugs could be detected in the
      receptor phase from either apical (AP) to basolateral (BL) or BL to AP studies.
      However, the appearance of linezolid in the receptor phase was biphasic with an
      initial rapid phase suggesting that the prodrugs were indeed more permeable, and
      for a short period, some prodrug was able to permeate in competition with
      conversion to linezolid on the donor phase surface. It appears that the prodrug
      was able to permeate was rapidly converted to linezolid prior to acceptor phase
      appearance. The second slower phase was due to the permeability of the donor
      phase-formed linezolid, with the slopes similar to those from control experiments
      with linezolid. The limitations and possible utility of oral sulfenamide prodrugs
      are discussed.

PMID- 22374831
TI  - Assembly of molecular "layered" heteropolyoxometalate architectures.
AB  - Neoclassical architecture: A new family of heteropolyoxometalates with "pagoda"
      shaped building blocks [Te(n)W(6n+3)O(21n+12)]((6+2n)-) (n=1, 2, 3) was
      discovered by adding {TeW(6)O(21)} layers on a classic {TeW(9)O(33)} fragment.
      Linking of the units allowed the generation of nanostructured clusters whose
      gross conformation is cation controlled. Studies of the redox behaviors of the
      multi-layered clusters indicate that the Te(IV) template is redox-active.

PMID- 22374832
TI  - Galvanic replacement reactions of active-metal nanoparticles.
AB  - We present a systemic investigation of a galvanic replacement technique in which
      active-metal nanoparticles are used as sacrificial seeds. We found that different
      nanostructures can be controllably synthesized by varying the type of more noble
      metal ions and liquid medium. Specifically, nano-heterostructures of noble metal
      (Ag, Au) or Cu nanocrystals on active-metal (Mg, Zn) cores were obtained by the
      reaction of active-metal nanoparticles with more noble-metal ions in ethanol; Ag
      nanocrystal arrays were produced by the reaction of active-metal nanoparticles
      with Ag(+) ions in water; spongy Au nanospheres were generated by the reaction of
      active-metal nanoparticles with AuCl(4)(-) ions in water; and SnO(2)
      nanoparticles were prepared when Sn(2+) were used as the oxidant ions. The key
      factors determining the product morphology are shown to be the reactivity of the
      liquid medium and the nature of the oxidant-reductant couple, whereas Mg and Zn
      nanoparticles played similar roles in achieving various nanostructures. When
      microsized Mg and Zn particles were used as seeds in similar reactions, the
      products were mainly noble-metal dendrites. The new approach proposed in this
      study expands the capability of the conventional nanoscale galvanic replacement
      method and provides new avenues to various structures, which are expected to have
      many potential applications in catalysis, optoelectronics, and biomedicine.

PMID- 22374833
TI  - Tympanic membrane retraction: An endoscopic evaluation of staging systems.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this work were to assess inter- and
      intraobserver variability of different staging systems for tympanic membrane (TM)
      retraction using otoendoscopy in children at risk of retraction from cleft
      palate, to compare hearing level with stage of retraction, and to propose optimum
      characteristics for monitoring TM retraction with endoscopy. STUDY DESIGN: Cross
      sectional study. METHODS: Endoscopic images of 245 TMs of children with cleft
      palate (mean age, 13.0 years) were assessed on two separate occasions by six
      observers using the Sade and Erasmus staging systems for pars tensa retraction
      and Tos system for pars flaccida retraction. Intra- and interobserver agreements
      were calculated. Extent of TM retraction was compared with hearing threshold. TMs
      with middle ear effusion, tympanostomy tubes, or perforation were excluded.
      RESULTS: A total of 108 ear drums (44%) were rated as having pars tensa and/or
      flaccida retraction. Intraobserver agreement was fair to moderate (kappa = 0.3
      0.37, P < .001) for the different staging systems and interobserver agreement
      slight to moderate (0.18-0.41 P < .001). Conductive hearing loss (four-tone
      average air-bone gap >25 dB HL) was present in 11 ears (15%). No correlation
      between hearing threshold and retraction stage was found. Isolated tensa
      retraction onto the promontory increased hearing threshold more than retraction
      involving the incus (P = .02; analysis of variance). CONCLUSIONS: Endoscopic
      image capture may provide a clear objective record of TM retraction, but current
      staging systems have unsatisfactory reliability when applied to such images, and
      retraction stage correlates poorly with hearing threshold. Modification of
      retraction assessment to improve validity and clinical relevance is proposed.

PMID- 22374834
TI  - Accurate quantification of water-macromolecule exchange induced frequency shift:
      effects of reference substance.
AB  - Water-macromolecule exchange induces a bulk water frequency shift contributing to
      the contrast in phase imaging. For separating the effects of the water
      macromolecule exchange and the macromolecule susceptibility, appropriate internal
      or external references are needed. In this study, two internal reference
      compounds, 2,2,3,3-tetradeuterio-3-trimethylsilyl-propionate (TMSP) and 1,4
      dioxane, were used to study the macromolecule-dependent water frequency shift in
      a bovine serum albumin (BSA)-water system in detail. For TMSP, the water
      macromolecule exchange shift depended on both the BSA and the reference
      concentration and stabilized to a value of 0.025 ppm/mM (298 K, TMSP
      concentrations > 30 mM). For dioxane, the dependency of the water-macromolecule
      exchange shift on the BSA concentration is independent of dioxane at low
      concentrations. The resulting shift was smaller (0.009 ppm/mM) when compared with
      using higher TMSP concentrations as reference. This discrepancy might be due to
      additional dioxane-water interactions. Measurements with an external chloroform
      reference in a coaxial geometry showed a shift of -0.013 ppm/mM resulting from
      the opposing effects of macromolecules in water exchange-induced shift and
      diamagnetic susceptibility shift. All these effects should be considered in the
      interpretation of tissue phase contrast. From the experimental data, the
      equilibrium binding constant between BSA and TMSP has been quantified to be K(d)
      = 1.3 +/- 0.4, and the estimated number of interaction sites for BSA is 12.7 +/-
      2.6.

PMID- 22374835
TI  - Development and validation of an HPLC-UV method for simultaneous determination of
      zidovudine, lamivudine, and nevirapine in human plasma and its application to
      pharmacokinetic study in human volunteers.
AB  - A simple, rapid, and sensitive high performance liquid chromatographic method
      with UV detection has been developed and validated according to the FDA
      guidelines for the quantitation of zidovudine (ZDV), lamivudine (LMV), and
      nevirapine (NVR) in human plasma. The sample was prepared by simple liquid-liquid
      extraction. Chromatographic separation was carried out in a Hypersil BDS, C(18)
      column (250 mm * 4.6 mm; 5 um particle size) with simple mobile phase composition
      of 0.1 M ammonium acetate buffer in 0.5% acetic acid, v/v and methanol (40:60,
      v/v) at a flow rate of 0.85 ml min(-1) where detector was set at 270 nm with a
      total run time of 10 min which is very short for simultaneous estimation of three
      analytes in plasma. The method was linear over the concentration range of 50
      3000, 50-2000 and 10-3000 ng ml(-1) with lower limit of quantifications (LLOQ) of
      50, 50, and 10 ng ml(-1) for ZDV, LMV, and NVR, respectively. Accuracy and
      precision values of both within-run and between-run obtained from six different
      sets of three quality control (QC) samples along with the LLOQ analyzed in
      separate occasions for all the analytes ranged from 94.47-99.71% and 0.298
      3.507%, respectively. Extraction recovery of analytes in plasma samples was above
      90.16%. In stability tests, all the analytes in human plasma were stable during
      storage and assay procedure. The developed and validated method was successfully
      applied to quantitative determination of the three analytes in plasma for
      pharmacokinetic study in 12 healthy human volunteers.

PMID- 22374836
TI  - Azafullerene C59N-phthalocyanine dyad: synthesis, characterisation and
      photoinduced electron transfer.
AB  - The synthesis of a new azafullerene C(59)N-phthalocyanine (Pc) dyad is described.
      The key step for the synthesis of the C(59)N-Pc dyad was the formation of the
      C(59)N-based carboxylic acid, which was smoothly condensed with hydroxy-modified
      Pc. The structure of the C(59)N-Pc dyad was verified by (1)H and (13)C NMR
      spectroscopy, IR spectroscopy, UV/Vis spectroscopy and MS measurements. The
      photophysical and electrochemical properties of the C(59)N-Pc dyad were
      investigated in both polar and non-polar solvents by steady state and time
      resolved photoluminescence and absorption spectroscopy, as well as by cyclic
      voltammetry. Different relaxation pathways for the photoexcited C(59)N-Pc dyad,
      as a result of changing the solvent polarity, were found, thus giving rise to
      energy-transfer phenomena in non-polar toluene and charge-transfer processes in
      polar benzonitrile. Finally, the detailed quenching mechanisms were evaluated and
      compared with that of a C(60)-Pc dyad, which revealed that the different excited
      state energies and reduction potentials of the two fullerene spheres (i.e. C(59)N
      vs. C(60)) strongly diverged in the deactivation pathways of the excited states
      of the corresponding phthalocyanine dyads.

PMID- 22374837
TI  - Osteoblast response to puerarin-loaded porous titanium surfaces: an in vitro
      study.
AB  - Recent studies demonstrate puerarin stimulates bone formation, suggesting its
      potential application in dental implantology field. The aim of this study was to
      investigate effects of puerarin-loaded titanium surfaces on the promotion of
      osteogenesis in preosteoblasts (MC3T3-E1). Puerarin was prepared onto titanium
      surfaces with varying concentration (10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M)
      by biomimetic calcium phosphate deposition process. Surface characteristics were
      performed by field-emission scanning electron microscope (FSEM), X-ray
      diffractometer (XRD), and Fourier transform infrared spectroscopy (FTIR).
      Puerarin concentration in the coatings was performed by High-performance liquid
      chromatograph (HPLC) analyses. FSEM observation showed puerarin concentration
      influenced formation of sharp flakes in the coating. The size of flakes decreased
      with increase of puerarin concentrations. XRD and FTIR examinations demonstrated
      the puerarin concentration did not affect the chemical compositions of coatings,
      which composed of octacalcium phosphate (OCP). Puerarin concentration on the
      surfaces of 10(-8) M group was 10.22 +/- 0.32 ng/cm(2) . Puerarin had an
      increased effect on MC3T3-E1 ALP activities. Significant differences were found
      in 10(-8) and 10(-7) M groups on day 4, 10(-8) , 10(-7) , and 10(-6) M groups on
      day 7, and 10(-8) on day 14. In Type I collagen synthesis assay, 10(-9) and 10(
      8) M on day 7, 10(-8) on day 14 showed significant differences compared with
      control group. Furthermore, this stimulatory effect of puerarin was also observed
      in osteocalcin release assay (p < 0.05, at 10(-8) M and 10(-7) M, maximal at 10(
      8) M). These results indicate puerarin-loaded titanium surfaces promote
      accelerated osteogenic differentiation of preosteoblasts, which has the potential
      to improve the nature of osseointegration.

PMID- 22374838
TI  - Rock-salt-type crystal of thermally contracted C60 with encapsulated lithium
      cation.
AB  - Rock solid: fullerene-encapsulated Li(+) (Li(+)@C(60)) is an alkaline cation
      owing to the spherical shape and positive charge. Li(+)@C(60) crystallizes as a
      rock-salt-type crystal in the presence of PF(6)(-). The orientations of C(60) and
      PF(6)(-) (orange) are perfectly ordered below 370 K, and Li(+) (purple) hops
      within the cage. At temperatures below 100 K two Li(+) units are localized at two
      polar positions within each C(60) .

PMID- 22374839
TI  - Perspective on improving passive human intestinal absorption.
AB  - Methods such as pH adjustment, cosolvency, complexation, and micellization are
      routinely used to increase the concentration of dissolved drug in the
      gastrointestinal (GI) lumen over that of a saturated solution. However, these
      solubilizing agents also reduce the membrane-water distribution coefficient so
      that the membrane transport rate is not changed. Also, dilution of a formulation
      upon administration results in: (1) a pH change toward that of the GI fluid, (2)
      an exponential decrease in cosolvency, and (3) disassociation of complexes and
      the disintegration of micelles. As a result, these solubilizing agents cannot be
      expected to produce any increase in membrane transport-limited drug absorption
      over that of a suspension of unformulated drug.

PMID- 22374840
TI  - Unifying metal- and organocatalysis for asymmetric oxidative iminium activation:
      a relay catalytic system enabling the combined allylic oxidation of alcohols and
      prolinol ether catalyzed iminium reactions.
AB  - A multicatalytic system consisting of tetrapropylammonium perruthenate/N
      methylmorpholine N-oxide (TPAP/NMO) as oxidant, and diarylprolinol TMS-ether as
      chiral amine catalyst, has been developed and applied in the efficient
      construction of valuable chiral molecules. The one-pot domino reactions
      elaborated in the present study are based on the in situ generation of alpha,beta
      unsaturated aldehydes from allylic alcohols and their subsequent use in various
      asymmetric transformations (e.g., cyclopropanation, Michael addition, Michael
      addition/acetalization). TPAP as a substrate-selective redox catalyst is well
      tolerated by the amine catalyst and the domino reactions proceed in good yields
      and high enantioselectivities. The compatibility of metal and organocatalysis
      presented herein widens the scope of asymmetric iminium catalysis.

PMID- 22374841
TI  - Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in
      acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles
      are determined by the disease, patient age, and anti-leukemic treatment.
AB  - Heat shock protein (HSP) 70 and HSP90 are released by primary human acute myeloid
      leukemia (AML) cells during stress-induced spontaneous in vitro apoptosis. The
      AML cells also show constitutive release of several cytokines and the systemic
      serum levels of several soluble mediators are altered in patients with untreated
      AML. In the present study, we have investigated serum levels of HSP70/HSP90 and
      the serum cytokine profiles of patients with untreated AML and patients receiving
      AML-stabilizing palliative treatment based on all-trans retinoic acid (ATRA) plus
      valproic acid. Patients with untreated AML showed increased HSP90 levels and a
      distinct serum cytokine profile when compared with healthy controls, and low pre
      therapy HSP90 levels were associated with a prolonged survival during treatment
      with ATRA + valproic acid + theophyllin. Hierarchical cluster analysis showed a
      close association between HSP70, HSP90, IL-1 receptor antagonist (IL-1ra), and
      hepatocyte growth factor (HGF) levels. Furthermore, disease-stabilizing therapy
      altered the serum-cytokine profile, but the correlations between HSP70/HSP90/IL
      1ra/HGF were maintained only when ATRA + valproic acid were combined with
      theophyllin but not when combined with cytarabine. We conclude that both HSP
      levels and serum cytokine profiles are altered and may represent possible
      therapeutic targets or prognostic markers in human AML.

PMID- 22374842
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in nasal
      lavage after an inhalation challenge with flour.
AB  - OBJECTIVES/HYPOTHESIS: The existence of nasal mucosa remodeling in allergic
      rhinitis is controversial. Few data are available on the dynamics of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in
      nasal fluid after an allergen challenge. We examined whether an immediate
      allergic reaction that induces nasal congestion and inflammation is able to also
      induce changes in remodeling parameters in nasal fluid. STUDY DESIGN: Controlled
      experimental study. METHODS: Ten patients with allergic occupational rhinitis due
      to flour underwent a control and active inhalation challenge with serial
      monitoring of nasal congestion and nasal symptoms with acoustic rhinometry and a
      visual analogue scale. Levels of remodeling markers (MMP-2, MMP-7, MMP-9, MMP-13,
      TIMP-1, TIMP-2) and inflammatory cells in nasal fluid were measured before the
      challenge and at 30 minutes, 6 hours, and 24 hours following the challenge.
      RESULTS: In contrast to the control challenge, the flour challenge induced nasal
      symptoms and significant decreases in nasal volume in all subjects. After the
      flour challenge, a significant increase in nasal levels of TIMP-2 and a
      nonsignificant increase in TIMP-1 levels were observed, whereas no significant
      changes in nasal levels of MMPs were documented. CONCLUSIONS: This study showed
      that after an inhalation challenge with an occupational allergen, the nasal
      mucosa displayed an imbalance in favor of TIMPs enzymes activity as compared to
      MMPs enzymes activity, represented in an increase in nasal levels of TIMP-2
      during the course of the early reaction following the allergen challenge.

PMID- 22374843
TI  - Refocused double-quantum editing for lactate detection at 7 T.
AB  - Lactate is an important marker for anaerobic glucose metabolism, and it is
      therefore of particular interest in, for example, cerebral ischemia, skeletal
      muscle disorders, and in the monitoring of oncology treatments. However, the in
      vivo detection of lactate with magnetic resonance spectroscopy is complicated by
      the overlap of the low-intensity lactate methyl resonance with lipid signal.
      Therefore, double-quantum filters have been employed to dephase the overlapping
      lipid signal, as they allow for a very high lipid suppression efficiency. For
      reliable lactate detection in lipid-rich environment, very large crushing
      gradients have to be employed to dephase the lipid signal under the noise level.
      Double-quantum filters are generally associated with signal loss of the
      metabolite of interest. For lactate, half of the signal is lost by selecting
      either the double- or the zero-quantum coherences. Moreover, owing to incomplete
      refocusing, traditional double-quantum filters with very large crusher gradients
      exhibit additional loss of the already low-lactate signal. In this study, a
      refocused double-quantum filter is described, which does not suffer from this
      source of additional signal loss. Therefore, it becomes possible to detect
      lactate at lower concentrations, or in lipid-rich environments. Lactate
      measurements are shown in the human calf muscle at 7 T.

PMID- 22374844
TI  - A validated HPLC method for the simultaneous determination of naftidrofuryl
      oxalate and its degradation product (metabolite), naftidrofuryl acid:
      applications to pharmaceutical tablets and biological samples.
AB  - A simple, sensitive, and selective reverse phase-high performance liquid
      chromatography (RP-HPLC) method was developed and validated for the simultaneous
      determination of naftidrofuryl oxalate (NF) and its hydrolytic degradation
      product (metabolite), naftidrofuryl acid (NFA). Chromatographic separation was
      achieved on Spheri-5 RP-C8 (5 um) (220 * 4.6 mm i.d.) column using a mobile phase
      composed of acetonitrile, 0.05 M sodium acetate and triethylamine (40 : 60 : 0.1,
      by volume) adjusted to pH 5.5 using glacial acetic acid. The mobile phase was
      pumped at flow rate 1.5 ml/min. The UV detector was set at 225 nm and
      quantification of the analytes was based on measuring the peak areas. The method
      was proved to be accurate and precise with linearity ranges of 0.1-25 and 0.2-25
      ug ml(-1) for NF and NFA, respectively. The limits of detection were 0.03 and
      0.04 ug ml(-1) for NF and NFA, respectively. The method was applied to serve
      three goals: (1) stability-indicating assay of the parent drug NF in its
      pharmaceutical formulation, (2) determination of the degradation product NFA down
      to a level of 0.005% in the presence of large excess of the parent drug, and (3)
      drug monitoring of naftidrofuryl and its metabolite, naftidrofuryl acid, in human
      plasma/urine samples taken from a healthy volunteer treated with 200 mg oral dose
      of naftidrofuryl oxalate. The proposed method proved to be accurate, precise, and
      reliable in all these application fields.

PMID- 22374845
TI  - Integration of the OpenIGTLink network protocol for image-guided therapy with the
      medical platform MeVisLab.
AB  - BACKGROUND: OpenIGTLink is a new, open, simple and extensible network
      communication protocol for image-guided therapy (IGT). The protocol provides a
      standardized mechanism to connect hardware and software by the transfer of
      coordinate transforms, images, and status messages. MeVisLab is a framework for
      the development of image processing algorithms and visualization and interaction
      methods, with a focus on medical imaging. METHODS: The paper describes the
      integration of the OpenIGTLink network protocol for IGT with the medical
      prototyping platform MeVisLab. The integration of OpenIGTLink into MeVisLab has
      been realized by developing a software module using the C++ programming language.
      RESULTS: The integration was evaluated with tracker clients that are available
      online. Furthermore, the integration was used to connect MeVisLab to Slicer and a
      NDI tracking system over the network. The latency time during navigation with a
      real instrument was measured to show that the integration can be used clinically.
      CONCLUSIONS: Researchers using MeVisLab can interface their software to hardware
      devices that already support the OpenIGTLink protocol, such as the NDI Aurora
      magnetic tracking system. In addition, the OpenIGTLink module can also be used to
      communicate directly with Slicer, a free, open source software package for
      visualization and image analysis.

PMID- 22374847
TI  - Selective hydrogenation of alpha,beta-unsaturated aldehydes catalyzed by amine
      capped platinum-cobalt nanocrystals.
AB  - More Greasy, more selective: amine-capped Pt(3)Co nanocatalysts were synthesized
      and used for the hydrogenation of cinnamaldehyde (CAL). Capping the catalysts
      with amines that contain long carbon chains results in an ordered surface
      "array", in which high selectivity towards C=O hydrogenation can be achieved
      because the C=C bond in CAL does not interact with the surface. The longer the
      carbon chains in the amine, the higher the selectivity.

PMID- 22374846
TI  - Adipogenesis on biphasic calcium phosphate using rat adipose-derived mesenchymal
      stem cells: in vitro and in vivo.
AB  - Developing adipose tissue-engineered construct to mend soft tissue defects
      arising from traumatic injury, tumor resections, and maxillofacial abnormalities
      is of prime importance in plastic and reconstructive surgical procedures. It is
      apparent that the clinical outcome of classic techniques like adipose tissue
      transplantation is unpredictable, with graft resorption, lack of vascularization,
      and impaired functionality. In this prospective, the concept of tissue
      engineering was adopted to fabricate a combination product with biphasic calcium
      phosphate (BCP) and rat adipose-derived mesenchymal stem cells (ASCs) toward the
      development of an adipose tissue construct. BCP, a combination of hydroxyapatite
      and alpha-tricalcium phosphate, was characterized for its physiochemical
      properties, and ASCs were characterized for their stemness. The cell-ceramic
      interactions were demonstrated in vitro, whereas adipogenesis was picturesquely
      depicted by Nile red-stained multilocular adipocyte-like cells. Subsequently, the
      three-dimensional cell-ceramic-engineered construct was implanted in the rat
      dorsal muscle for a period of 3 weeks to demonstrate the efficacy of the tissue
      construct in vivo. Interestingly, the histology of the postimplanted tissue
      construct revealed the distribution of chicken wire net-like fat cells within the
      vicinity of the construct. The efficacy of cell transplantation via the scaffold
      was traced using fluorescent in situ hybridization by labeling the Y chromosome.
      Thus, the ceramic-based construct may be a good option for reconstruction
      therapies.

PMID- 22374848
TI  - Topical glucocorticoid reduces the topical decongestant-induced histologic
      changes in an animal model nasal mucosa.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the histologic consequences of simultaneous
      nasal glucocorticosteroid and xylometazoline HCl administration in the rabbit
      nasal mucosa. STUDY DESIGN: Prospective randomized study. METHODS: Twenty New
      Zealand male rabbits were randomly placed into three groups: group I, control (n
      = 6); group II, xylometazoline HCl (n = 8); or group III, xylometazoline HCl
      fluticasone furoate (n = 6). Group I received no treatment. Groups II and III
      received two intranasal puffs of xylometazoline HCl 0.5 mg/mL twice daily or two
      puffs of xylometazoline HCl 0.5 mg/mL twice daily plus one puff of 27.5 MUg
      fluticasone furoate twice daily to each nostril (110 MUg), respectively. At the
      end of 3 weeks, the rabbits were sacrificed. The mucosa of the nasal cavities was
      excised. Specimen sections (5 MUm) were stained with hematoxylin and eosin,
      mucicarmine, and Gomori one-step trichrome and were examined under a light
      microscope. The presence of edema, congestion, inflammatory cell infiltration,
      nasociliary loss, epithelial and nerve-ending degeneration, and goblet cell
      increase were evaluated semiquantitatively (grades 0-3). RESULTS: Statistically
      significant differences were detected between groups II and III in terms of
      edema, congestion, inflammatory cell infiltration, nasociliary loss, and
      epithelial degeneration (P = .006, P = .049, P = .015, P = .014, and P = .049,
      respectively). Nerve-ending degeneration, goblet cell increase, and quantitative
      goblet and neutrophil cell counts did not yield statistically significant
      differences between groups II and III (P = .137, P = .580, P = .770, and P =
      .616, respectively). CONCLUSIONS: The combined simultaneous intranasal
      administration of xylometazoline HCl and fluticasone furoate appears to be
      beneficial in minimizing the long-term usage-associated congestion, edema,
      inflammatory cell infiltration, epithelial degeneration, and nasociliary loss in
      the rabbit model nasal mucosa.

PMID- 22374849
TI  - Transmetallation versus beta-hydride elimination: the role of 1,4-benzoquinone in
      chelation-controlled arylation reactions with arylboronic acids.
AB  - The formation of an atypical, saturated, diarylated, Heck/Suzuki, domino product
      produced under oxidative Heck reaction conditions, employing arylboronic acids
      and a chelating vinyl ether, has been investigated by DFT calculations. The
      calculations highlight the crucial role of 1,4-benzoquinone (BQ) in the reaction.
      In addition to its role as an oxidant of palladium, which is necessary to
      complete the catalytic cycle, this electron-deficient alkene opens up a low
      energy reaction pathway from the post-insertion sigma-alkyl complex. The
      association of BQ lowers the free-energy barrier for transmetallation of the
      sigma-alkyl complex to create a pathway that is energetically lower than the
      oxidative Heck reaction pathway. Furthermore, the calculations showed that the
      reaction is made viable by BQ-mediated reductive elimination and leads to the
      saturated diarylated product.

PMID- 22374851
TI  - Fusarium: A potential cause of chronic rhinosinusitis?

PMID- 22374850
TI  - Multiorgan failure and bone marrow necrosis in three adults with sickle cell
      beta+ -thalassemia.

PMID- 22374852
TI  - 1H and 13C{1H} NMR spectral parameters of sulfur mustards, nitrogen mustards, and
      lewisites: computing and predicting of reference spectra for chemical
      identification.
AB  - The (1)H and (13)C{(1)H} chemical shifts and (1)H spin-spin couplings of sulfur
      mustards, nitrogen mustards, and lewisites scheduled in the Chemical Weapons
      Convention, and those of bis(2-chloromethyl)disulfide, were determined in
      CDCl(3), CD(2)Cl(2), and (CD(3))(2)CO. Accurate parameters of this kind of series
      can be used for evaluating the current molecular modeling programs and the
      chemical shift and coupling constant prediction possibilities of the programs.
      Several prediction tests were made with commercial programs, and the results are
      reported here.

PMID- 22374853
TI  - Helicobacter pylori genotype and polymorphisms in DNA repair enzymes: where do
      they correlate in gastric cancer?
AB  - BACKGROUND AND OBJECTIVES: One of the mechanisms proposed by which H. pylori
      causes gastric cancer (GC) is through DNA damage due to chronic inflammation.
      Genomic integrity is guaranteed by repair enzymes such as APE-1, OGG-1, and PARP
      1. Host genetic polymorphisms associated with the bacterial strain may influence
      the ability to repair the damage, contributing to the development of H. pylori
      associated GC. The aim of this study was to determine the association of the
      polymorphisms APE-1 (T2197G), OGG-1 (C1245G), and PARP-1 (A40676G) with H. pylori
      genotype in 109 patients with GC. METHODS: Polymorphism was assessed by
      polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)
      and H. pylori detection/genotyping by PCR. RESULTS: In the intestinal subtype,
      PARP-1 wild-type was more frequent (P=0.001) in patients >50 years old. The
      repair enzymes genotypes analyzed in combination showed that the less pathogenic
      strains are associated with the APE-1 polymorphic allele and, unexpectedly, with
      PARP-1 wild-type, but this last one associated with APE-1 polymorphic allele or
      in older patients. CONCLUSIONS: Our results indicate the importance of H. pylori
      and APE-1 genotypes in the gastric carcinogenesis. Also, support the hypothesis
      of a decrease of PARP-1 wild-type activity in older individuals. Taken together
      these data may be an important clue to understand the role of low-virulence
      strains of H. pylori in gastric carcinogenesis and point the importance to
      analyze the polymorphisms as a group.

PMID- 22374854
TI  - Comparison of different reconstruction algorithms for three-dimensional
      ultrasound imaging in a neurosurgical setting.
AB  - BACKGROUND: Freehand three-dimensional ultrasound imaging (3D-US) is increasingly
      used in image-guided surgery. During image acquisition, a set of B-scans is
      acquired that is distributed in a non-parallel manner over the area of interest.
      Reconstructing these images into a regular array allows 3D visualization.
      However, the reconstruction process may introduce artefacts and may therefore
      reduce image quality. The aim of the study is to compare different algorithms
      with respect to image quality and diagnostic value for image guidance in
      neurosurgery. METHODS: 3D-US data sets were acquired during surgery of various
      intracerebral lesions using an integrated ultrasound-navigation device. They were
      stored for post-hoc evaluation. Five different reconstruction algorithms, a
      standard multiplanar reconstruction with interpolation (MPR), a pixel nearest
      neighbour method (PNN), a voxel nearest neighbour method (VNN) and two voxel
      based distance-weighted algorithms (VNN2 and DW) were tested with respect to
      image quality and artefact formation. The capability of the algorithm to fill
      gaps within the sample volume was investigated and a clinical evaluation with
      respect to the diagnostic value of the reconstructed images was performed.
      RESULTS: MPR was significantly worse than the other algorithms in filling gaps.
      In an image subtraction test, VNN2 and DW reliably reconstructed images even if
      large amounts of data were missing. However, the quality of the reconstruction
      improved, if data acquisition was performed in a structured manner. When
      evaluating the diagnostic value of reconstructed axial, sagittal and coronal
      views, VNN2 and DW were judged to be significantly better than MPR and VNN.
      CONCLUSION: VNN2 and DW could be identified as robust algorithms that generate
      reconstructed US images with a high diagnostic value. These algorithms improve
      the utility and reliability of 3D-US imaging during intraoperative navigation.

PMID- 22374856
TI  - A double addition of Ln-H to a carbon-carbon triple bond and competitive
      oxidation of ytterbium(II) and hydrido centers.
AB  - Addition of two Ln-H bonds of an Yb(II) hydrido complex supported by bulky
      amidinate ligand to a C=C bond lead to the formation of 1,2-dianionic bibenzyl
      fragment. Both Yb(II) and hydrido centers are oxidized under the reaction
      conditions. The resulting Yb(II)-eta(6) -arene interaction is surprisingly
      robust: the arene cannot be replaced from the metal coordination sphere when
      treated with Lewis bases.

PMID- 22374855
TI  - RNA decay: a novel therapeutic target in bacteria.
AB  - The need for novel antibiotics is greater now than perhaps any time since the pre
      antibiotic era. Indeed, the recent collapse of most pharmaceutical antibacterial
      groups, combined with the emergence of hypervirulent and pan-antibiotic-resistant
      bacteria have, in effect, created a 'perfect storm' that has severely compromised
      infection treatment options and led to dramatic increases in the incidence and
      severity of bacterial infections. To put simply, it is imperative that we develop
      new classes of antibiotics for the therapeutic intervention of bacterial
      infections. In that regard, RNA degradation is an essential biological process
      that has not been exploited for antibiotic development. Herein we discuss the
      factors that govern bacterial RNA degradation, highlight members of this
      machinery that represent attractive antimicrobial drug development targets and
      describe the use of high-throughput screening as a means of developing
      antimicrobials that target these enzymes. Such agents would represent first-in
      class antibiotics that would be less apt to inactivation by currently encountered
      enzymatic antibiotic-resistance determinants.

PMID- 22374857
TI  - Chromosomal variation in lymphoblastoid cell lines.
AB  - Tens of thousands of lymphoblastoid cell lines (LCLs) have been established by
      the research community, providing nearly unlimited source material from samples
      of interest. LCLs are used to address questions in population genomics,
      mechanisms of disease, and pharmacogenomics. Thus, it is of fundamental
      importance to define the extent of chromosomal variation in LCLs. We measured
      variation in genotype and copy number in multiple LCLs derived from peripheral
      blood mononuclear cells (PBMCs) of single individuals as well as two comparison
      groups: (1) three types of differentiated cell lines (DCLs) and (2) triplicate
      HapMap samples. We then validated and extended our findings using data from a
      large study consisting of samples from blood or LCLs. We observed high
      concordances between genotypes and copy number estimates within all sample
      groups. While the genotypes of LCLs tended to faithfully reflect the genotypes of
      PBMCs, 13.7% (4 of 29) of immortalized cell lines harbored mosaic regions greater
      than 20 megabases, which were not present in PBMCs, DCLs, or HapMap replicate
      samples. We created a list of putative LCL-specific changes (affecting regions
      such as immunoglobulin loci) that is available as a community resource.

PMID- 22374858
TI  - Highly efficient extraction and oxidative desulfurization system using
      Na7H2LaW10O36?32 H2O in [bmim]BF4 at room temperature.
AB  - Highly efficient, deep desulfurization of model oil containing dibenzothiophene
      (DBT), benzothiophene (BT), or 4,6-dimethyldibenzothiophene (4,6-DMDBT) has been
      achieved under mild conditions by using an extraction and catalytic oxidative
      desulfurization system (ECODS) in which a lanthanide-containing polyoxometalate
      Na(7)H(2)LnW(10)O(36)?32 H(2)O (LnW(10); Ln = Eu, La) acts as catalyst,
      [bmim]BF(4) (bmim = 1-butyl-3-methylimidazolium) as extractant, and H(2)O(2) as
      oxidant. Sulfur removal follows the order DBT>4,6-DMDBT>BT at 30  degrees C. DBT
      can be completely oxidized to the corresponding sulfone in 25 min under mild
      conditions, and the LaW(10)/[bmim]BF(4) system could be recycled for ten times
      with only slight decrease in activity. Thus, LaW(10) in [bmim]BF(4) is one of the
      most efficient systems for desulfurization using ionic liquids as extractant
      reported so far.

PMID- 22374860
TI  - Early changes in apparent diffusion coefficients predict radiosensitivity of
      human nasopharyngeal carcinoma xenografts.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to predict the radiosensitivity of human
      nasopharyngeal carcinoma xenografts in nude mice models through an examination of
      early changes in apparent diffusion coefficient (ADC) values. STUDY DESIGN:
      Randomized. METHODS: BALB/c-nu nude mice (n = 20) were divided into two groups
      that were subcutaneously injected with CNE1 or CNE2 cell lines. Xenograft volumes
      were measured after tumor formation, mice were scanned with a diffusion-weighted
      imaging sequence, and the mean ADC values were measured (ADC(0) ). Fifteen to 20
      hours after tumors received 15 Gy, mice were scanned again and ADC values (ADC(1)
      ) were measured. RESULTS: ADC(0) and ADC(1) values of the CNE1 group showed no
      significant difference (P = .692). The difference between the ADC(0) and ADC(1)
      values of the CNE2 group was statistically significant (P < .001). ADC(0) values
      of the two groups exhibited no statistically significant difference (P = .204).
      ADC(1) , ADC(1-0) , and DeltaADC of the two groups exhibited statistically
      significant differences (P < .001; P = .001 and .002, respectively). After
      irradiation, volume changes DeltaV(8) , DeltaV(10) , and DeltaV(12) of two groups
      were statistically different (all P < .001). Pearson correlation analysis showed
      ADC(1-0) and DeltaADC were positively correlated with DeltaV(8) , DeltaV(10) ,
      and DeltaV(12) . The cut point was found by means of a receiver operating
      characteristic curve, and the DeltaV(12) of the two redivided groups showed a
      statistically significant difference (P = .001). CONCLUSIONS: This study found
      that changes in ADC values correlated with volume changes after irradiation.
      Therefore, ADC values have the potential to predict the radiosensitivity of
      nasopharyngeal carcinoma xenografts.

PMID- 22374859
TI  - Acyl carrier protein structural classification and normal mode analysis.
AB  - All acyl carrier protein primary and tertiary structures were gathered into the
      ThYme database. They are classified into 16 families by amino acid sequence
      similarity, with members of the different families having sequences with
      statistically highly significant differences. These classifications are supported
      by tertiary structure superposition analysis. Tertiary structures from a number
      of families are very similar, suggesting that these families may come from a
      single distant ancestor. Normal vibrational mode analysis was conducted on
      experimentally determined freestanding structures, showing greater fluctuations
      at chain termini and loops than in most helices. Their modes overlap more so
      within families than between different families. The tertiary structures of three
      acyl carrier protein families that lacked any known structures were predicted as
      well.

PMID- 22374861
TI  - Cancer patients requiring interruption of long-term warfarin because of surgery
      or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses
      of low-molecular weight heparin.
AB  - No data are available regarding the management of cancer patients requiring
      interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose,
      we tested the efficacy and safety of fixed doses of low-molecular weight heparin
      (LMWH) in substitution of VKA because of invasive procedures or chemotherapy
      induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5
      +/- 1 days before surgery or chemotherapy. Heparin was given at prophylactic
      dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000
      UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated
      12 hr after surgery and VKA the day after. In patients receiving chemotherapy,
      LMWH was reinitiated 12/24 hr after obtaining a stable platelet count >= 30,000
      mmc(3) and VKA after a stable platelet count >= 50,000 mmc(3) . Thromboembolism
      and major bleeding events were recorded from the time of VKA suspension to 30 +/-
      2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4%
      at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent
      major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events
      occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four
      belonging to the high-risk and one to the low-risk group. Major bleeding occurred
      in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group
      (three during major surgery and two during chemotherapy). In conclusion, LMWH
      given at fixed subtherapeutic is a feasible and relatively safe approach for
      bridging therapy in cancer patients on long-term VKA.

PMID- 22374862
TI  - An isolable acyclic hemiacetal of ansamitocin P-3.
AB  - During impurity analysis of maytansinol (2), produced from the reduction of
      ansamitocin P-3 (AP-3, 1), a surprisingly stable acyclic hemiacetal (4) was
      isolated. A combination of 1D and 2D NMR experiments, along with liquid
      chromatography-mass spectrometry data was used to confirm the structure.
      Comparison of NMR data to the previously reported bridged acetal (3), a by
      product of AP-3 reduction, supports reassignment of the latter to the former.
      Additionally, ROESY data, in conjunction with minimum energy calculations,
      support intramolecular hydrogen bonding that is involved in stabilizing the
      hemiacetal. This report adds another example to the very short list of isolable
      acyclic hemiacetals.

PMID- 22374864
TI  - Mini-navigator: a new system for navigated deformity corrections.
AB  - BACKGROUND: The purpose of this study is to present a new navigation device for
      deformity correction surgery and to evaluate its accuracy compared with a
      conventional electromagnetic navigation system in tracking the orientation of
      synthetic bony fragments. METHODS: This system consists of three sensors and
      software which can be installed on any personal computer. One sensor is mounted
      about 1 m above the other sensors. The remaining two sensors are fixed to the
      bone fragments using Schanz screws. Data from all three sensors are computed
      using the software to estimate the change in position of the sensors. For the
      first part of the study 118 planned one and two plane deformities in 5 degrees 
      increments were created. For the second part of the study complex random 3
      dimensional deformities were created (300 valid measurements). RESULTS: The mean
      absolute differences between measurements of the electromagnetic and mini
      navigator were 1.8 +/- 1.9 degrees  in the coronal, 1.1 +/- 1.1 degrees  in the
      sagittal and 0.8 +/- 0.7 degrees  in the transverse plane. Absolute differences
      between mini-navigator and Fastrak measurements were significantly affected by
      the magnitude of the deformity (P < 0.0001) with better accuracy for lower
      deformities. CONCLUSIONS: We believe that this new technology is appealing,
      because of its high accuracy and lower planned costs compared with conventional
      navigation devices.

PMID- 22374865
TI  - Generating orally active galanin analogues with analgesic activities.
AB  - The endogenous neuropeptide galanin has anticonvulsant and analgesic properties
      mediated by galanin receptors expressed in the central and peripheral nervous
      systems. Our previous work showed that by combining truncation of the galanin
      peptide with N- and C-terminal modifications afforded analogues that suppress
      seizures or pain upon intraperitoneal (i.p.) administration. To generate orally
      active galanin analogues, the previously reported lead compound Gal-B2 (NAX 5055)
      was redesigned by 1) central truncation, (2) introduction of D-amino acids, and
      3) addition of backbone spacers. Analogue D-Gal(7-Ahp)-B2, containing 7
      aminoheptanoic acid as a backbone spacer and an oligo-D-lysine motif at the C
      terminus, exhibits anticonvulsant and analgesic activity post-i.p.
      administration. Oral administration of D-Gal(7-Ahp)-B2 demonstrates analgesic
      activity with decreases in both acute and inflammatory pain in the mouse formalin
      model of pain at doses as low as 8 mg kg(-1) .

PMID- 22374866
TI  - Preoperative embolization of replaced right hepatic artery prior to
      pancreaticoduodenectomy.
AB  - Aberrancy of the hepatic arterial anatomy is common. Because of its course
      directly adjacent to the head of the pancreas, a replaced right hepatic artery
      (RHA) is vulnerable to invasion by peri-pancreatic malignancies. Division of the
      RHA at the time of pancreaticoduodenectomy, however, may result in hepatic
      infarction and/or bilioenteric anastomotic complications. We report two cases of
      patients undergoing preoperative embolization of tumor encased replaced RHAs to
      allow for sufficient collateralization prior to pancreaticoduodenectomy.

PMID- 22374868
TI  - Structural basis of RNA binding by leucine zipper GCN4.
AB  - Recently, we showed that leucine zipper (LZ) motifs of basic leucine zipper
      (bZIP) transcription factors GCN4 and c-Jun are capable of catalyzing degradation
      of RNA (Nikolaev et al., PLoS ONE 2010; 5:e10765). This observation is intriguing
      given the tight regulation of RNA turnover control and the antiquity of bZIP
      transcription factors. To support further mechanistic studies, herein, we
      elucidated RNA binding interface of the GCN4 leucine zipper motif from yeast.
      Solution NMR experiments showed that the LZ-RNA interaction interface is located
      in the first two heptads of LZ moiety, and that only the dimeric (coiled coil) LZ
      conformation is capable of binding RNA. Site-directed mutagenesis of the LZ-GCN4
      RNA binding interface showed that substrate binding is facilitated by lysine and
      arginine side chains, and that at least one nucleophilic residue is located in
      proximity to the RNA phosphate backbone. Further studies in the context of full
      length bZIP factors are envisaged to address the biological relevance of LZ RNase
      activity.

PMID- 22374869
TI  - Kinetic and mechanistic investigations of the light induced formation of gold
      nanoparticles on the surface of TiO2.
AB  - The kinetics of the formation of gold nanoparticles on the surface of pre
      illuminated TiO(2) have been investigated using stopped-flow technique and steady
      state UV/Vis spectroscopy. Excess electrons were loaded on the employed nanosized
      titanium dioxide particles by UV-A photolysis in the presence of methanol serving
      as hole scavenger, stored on them in the absence of oxygen and subsequently used
      for the reduction of Au(III) ions. The formation of gold nanoparticles with an
      average diameter of 5 nm was confirmed after mixing of the TiO(2) nanoparticles
      loaded with electrons with aqueous solution of tetrachloroaureate (HAuCl(4)) by
      their surface plasmon absorbance band at 530 nm, as well as by XRD and HRTEM
      measurements. The rate of formation of the gold nanoparticles was found to be a
      function of the concentration of the gold ions and the concentration of the
      stored electrons, respectively. The effect of PVA as a stabilizer of the gold
      nanoclusters was also studied. The observed kinetic behavior suggests that the
      formation of the gold nanoparticles on the TiO(2) surface is an autocatalytic
      process comprising of two main steps: 1) Reduction of the gold ions by the stored
      electrons on TiO(2) forming gold atoms that turn into gold nuclei. 2) Growth of
      the metal nuclei on the surface of TiO(2) forming the gold particles.
      Interestingly, at higher TiO(2) electron loading the excess electrons are
      subsequently transferred to the deposited gold metal particles resulting in
      "bleaching" of their surface plasmon band. This bleaching in the surface plasmon
      band is explained by the Fermi level equilibration of the Au/TiO(2)
      nanocomposites. Finally, the reduction of water resulting in the evolution of
      molecular hydrogen initiated by the excess electrons that have been transferred
      to the previously formed gold particles has also been observed. The mechanism of
      the underlying multistep electron-transfer process has been discussed in detail.

PMID- 22374870
TI  - Prediction of nonrecovery in Bell's palsy using Sunnybrook grading.
AB  - OBJECTIVES/HYPOTHESIS: To develop a clinical prognostic model to identify Bell's
      palsy patients with risk for nonrecovery at 12 months. STUDY DESIGN: Data from a
      prospective, randomized, double-blind, placebo-controlled, multicenter study.
      METHODS: There were 829 patients with Bell's palsy randomized in a factorial
      fashion to treatment with prednisolone or no prednisolone. Facial function was
      assessed with the Sunnybrook grading scale. Univariate and multivariate logistic
      regression analyses at different time points were used to identify factors
      predicting nonrecovery, defined as Sunnybrook <70 at 12 months. Variables studied
      were age, gender, time to inclusion, prednisolone treatment, side of palsy, pain
      at inclusion, and Sunnybrook scores. Factors of predictable significance were
      used to construct prognostic models at baseline, days 11 to 17, and at 1 month.
      Receiver operating characteristics curves were created to test the predictive
      capacity of the models. RESULTS: At baseline, treatment with prednisolone or no
      prednisolone (P = .0005), age (P = .04) and the Sunnybrook score (P = .0002) were
      significant factors for predicting nonrecovery. The receiver operating
      characteristics area under the curve at baseline for these three variables was
      0.74 (sensitivity 0.83, specificity 0.57). At days 11 to 17 and at 1 month, the
      Sunnybrook score was the only significant predictive variable. The respective
      areas under the curves for the Sunnybrook score at these time points were 0.83
      (sensitivity 0.81, specificity 0.75) and 0.94 (sensitivity 0.91, specificity
      0.85). CONCLUSIONS: Sunnybrook grading at 1 month most accurately predicts
      nonrecovery at 12 months in Bell's palsy.

PMID- 22374872
TI  - Dynamic NMR of low-sensitivity fast-relaxing nuclei: (17)O NMR and DFT study of
      acetoxysilanes.
AB  - (17)O NMR is not routinely used for structure characterization, and kinetic
      studies of fluxional organic compounds are seldom undertaken because poor
      sensitivity and fast quadrupole relaxation are frequently regarded as intractable
      issues. This work shows how, nowadays, quantitative (17)O dynamic NMR studies on
      small organic molecules are feasible without enrichment being needed. It reports
      on acetoxysilanes, a class of fluxional compounds whose structure and dynamics
      were to be clarified. Natural abundance (17)O NMR spectra were recorded over a
      wide range of temperatures using standard instrumentation. The analysis relies on
      simple linewidth measurements and directly provides the activation parameters.
      The activation enthalpy is found to decrease with increasing number of acetoxy
      groups bound to silicon. Density functional theory calculations properly predict
      this trend and show that a single oxygen atom of the acetoxy group is bound to
      silicon, excluding chelation as binding mode, and that the dynamic process
      involves the shift of the silicon atom between the two oxygen atoms of the
      acetoxy group.

PMID- 22374871
TI  - miR-199b-5p directly targets PODXL and DDR1 and decreased levels of miR-199b-5p
      correlate with elevated expressions of PODXL and DDR1 in acute myeloid leukemia.

PMID- 22374875
TI  - A case-control comparison of lingual tonsillar size in children with and without
      Down syndrome.
AB  - OBJECTIVES/HYPOTHESIS: Lingual tonsillar hypertrophy is a common cause of
      persistent obstructive sleep apnea following adenotonsillectomy in the pediatric
      population and may be more prevalent in patients with Down syndrome (DS). We
      sought to quantify lingual tonsil size in pediatric DS patients and compare these
      findings to those of nonsyndromic children using cervical spine (c-spine)
      radiographs. STUDY DESIGN: Case control study. METHODS: Retrospective review of c
      spine radiographs from 105 pediatric DS patients and 89 age- and gender-matched
      non-DS controls was conducted. Films performed for possible airway compromise or
      trauma were excluded. Lingual tonsil size and narrowest lumen diameter of the
      nasopharynx, oropharynx, and hypopharynx were measured. RESULTS: Radiographically
      identifiable lingual tonsillar tissue was identified in 34% of children with DS
      and 30% of controls (P = .21); lingual tonsillar hypertrophy (>=10 mm) was seen
      in 5% and 0% respectively (P = .074). Nasopharyngeal diameter was smaller in
      patients with DS compared to controls (5.2 mm vs. 6.3 mm, P = .026), whereas
      lingual tonsil size was significantly larger in DS patients (2.1 mm vs. 0.8 mm, P
      = .0008). In multivariate analysis, lingual tonsil size was positively correlated
      with increasing age in the DS population (r = 0.38, P < .0001) but not in
      controls. CONCLUSIONS: Lingual tonsillar enlargement is more common in patients
      with DS than in controls, with an increased prevalence in older DS patients. C
      spine radiographs are routinely carried out in these children and appear to be
      useful in identifying lingual tonsillar hypertrophy. Further trials should be
      carried out to compare c-spine findings and physical exam or magnetic resonance
      imaging to validate this method of evaluation.

PMID- 22374877
TI  - Labor participation among patients with inflammatory bowel disease.
AB  - BACKGROUND: The aims of the present study are twofold. First, to describe labor
      participation rates of people with inflammatory bowel disease (IBD) in the
      Netherlands compared with the total Dutch population and to people with chronic
      illness in general. Second, to explore differences in labor participation among
      IBD patients and assess the potential impact of a number of characteristics of
      IBD patients on labor participation. METHODS: Data were obtained from a
      nationwide survey of individuals with IBD in the Netherlands. In all, 1115
      respondents completed the survey. Univariate, bivariate, and multinomial logistic
      regression analysis were conducted to identify factors predicting the number of
      hours worked by IBD patients. RESULTS: People with IBD do not participate less
      often in the labor market compared with the total Dutch population age 15 to 64.
      However, male patients age 45 to 64 less often have a fulltime job compared with
      age- and gender-matched reference groups from the general population. People with
      IBD are more likely to participate in the labor market than people with chronic
      illness in general. Gender, age, duration of illness, having a stoma or pouch,
      comorbidity, vitality, pain, and perceived personal control appear to be
      significant predictors of the number of hours worked. CONCLUSIONS: People with
      IBD in the Netherlands are as often employed as the general population, but among
      some gender/age categories fewer people work fulltime. Besides sociodemographic
      and illness characteristics, the perception of personal control over the illness
      explains differences in the number of hours worked. Strengthening IBD patients'
      control perceptions deserves attention.

PMID- 22374876
TI  - Ratcheting up protein translocation with anthrax toxin.
AB  - Energy-consuming nanomachines catalyze the directed movement of biopolymers in
      the cell. They are found both dissolved in the aqueous cytosol as well as
      embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine
      catalyzed biopolymer transport have revealed that these machines are equipped
      with molecular parts, including adjustable clamps, levers, and adaptors, which
      interact favorably with substrate polypeptides. Biological nanomachines that
      catalyze protein transport, known as translocases, often require that their
      substrate proteins unfold before translocation. An unstructured protein chain is
      likely entropically challenging to bind, push, or pull in a directional manner,
      especially in a way that produces an unfolding force. A number of ingenious
      solutions to this problem are now evident in the anthrax toxin system, a model
      used to study protein translocation. Here we highlight molecular ratchets and
      current research on anthrax toxin translocation. A picture is emerging of proton
      gradient-driven anthrax toxin translocation, and its associated ratchet mechanism
      likely applies broadly to other systems. We suggest a cyclical thermodynamic
      order-to-disorder mechanism (akin to a heat-engine cycle) is central to
      underlying protein translocation: peptide substrates nonspecifically bind to
      molecular clamps, which possess adjustable affinities; polypeptide substrates
      compress into helical structures; these clamps undergo proton-gated switching;
      and the substrate subsequently expands regaining its unfolded state
      conformational entropy upon translocation.

PMID- 22374878
TI  - Variability in the perilymphatic diffusion of gadolinium does not predict the
      outcome of intratympanic gentamicin in patients with Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: To assess the utility of imaging in planning intratympanic
      (IT) gentamicin (Gent) treatment in Meniere's disease (MD), we compared the
      dosage and outcomes of ITGent with the severity and extent of endolymphatic
      hydrops (EH), as evaluated by three-dimensional fluid-attenuated inversion
      recovery (3D-FLAIR) sequence in a 3-T magnetic resonance imaging (MRI) unit,
      after IT gadolinium administration. STUDY DESIGN: Retrospective review. METHODS:
      A total of 18 patients (10 males and 8 females; age, 28-78 years; median age,
      53.2 years) with definite MD participated in the investigation. The duration of
      the disease ranged from 8 months to 9 years (median, 2 years), with a prevalence
      of vertigo spells ranging from 0.8 to 8 per month (median, 2.2), as calculated in
      the last 6 months. A 3D-FLAIR MRI was performed 24 hours after IT injection of
      diluted gadobutrol. ITGent injection was performed within a variable period of
      time, from 1 week to 3 weeks after 3D-FLAIR MRI. The degree and extension of EH
      as evaluated by 3D-FLAIR MRI were compared with the number of injections
      necessary to cure vertigo attacks. Vertigo results, functional level scale
      modifications, variations in caloric excitability, and pure-tone average
      modifications. RESULTS: No statistically significant correlation was observed
      between severity of EH and outcomes of ITGent administration. CONCLUSIONS: The
      hypothesis of a reduced effect of Gent administered intratympanically in the
      presence of severe EH, owing to obstacled diffusion along the perilymphatic
      compartments, has not been confirmed in the present investigation.

PMID- 22374879
TI  - Gold- and silver-catalyzed reactions of propargylic alcohols in the presence of
      protic additives.
AB  - A wide range of primary, secondary and tertiary propargylic alcohols undergo a
      Meyer-Schuster rearrangement to give enones at room temperature in the presence
      of a gold(I) catalyst and small quantities of MeOH or 4-methoxyphenylboronic
      acid. The syntheses of the enone natural products isoegomaketone and daphenone
      were achieved using this reaction as the key step. The rearrangement of primary
      propargylic alcohols can readily be combined in a one-pot procedure with the
      addition of a nucleophile to the resulting terminal enone, to give beta-aryl,
      beta-alkoxy, beta-amino or beta-sulfido ketones. Propargylic alcohols bearing an
      adjacent electron-rich aryl group can also undergo silver-catalyzed substitution
      of the alcohol with oxygen, nitrogen and carbon nucleophiles. This latter
      reaction was initially observed with a batch of gold catalyst that was probably
      contaminated with small quantities of silver salt.

PMID- 22374880
TI  - da Vinci(r) single-site platform: anthropometrical, docking and suturing
      considerations for hysterectomy in the cadaver model.
AB  - BACKGROUND: The paper describes specific technical requirements, limitations,
      anthropometrical, docking and suturing considerations on the performance of
      robotic hysterectomy using the da Vinci(r) Single-Site Platform in the cadaver
      model METHODS: A data set was collected for each procedure including port
      placement, docking sequence, robotic arms placement and angles, robotic
      instrumentation, optimal ergonomics, operative time, and cadaver anthropometrical
      measurements. Pearson correlation coefficients were calculated to determine
      whether age, BMI or docking approach were correlated with docking difficulty and
      likelihood of successful procedure completion. Analysis of the data was performed
      using SPSS v19.0.0. RESULTS: The planned surgical procedure was successfully
      completed with single-port robotics in 87.5% of cases. High BMI was correlated
      with difficulty docking the robot, correlation coefficient 0.98. CONCLUSIONS:
      Further work is needed in the development and advancement of single-site robotic
      platforms, articulated instrumentation, and optics.

PMID- 22374881
TI  - Ceria foam with atomically thin single-crystal walls.

PMID- 22374882
TI  - Procedural pain and brain development in premature newborns.
AB  - OBJECTIVE: Preterm infants are exposed to multiple painful procedures in the
      neonatal intensive care unit (NICU) during a period of rapid brain development.
      Our aim was to examine relationships between procedural pain in the NICU and
      early brain development in very preterm infants. METHODS: Infants born very
      preterm (N=86; 24-32 weeks gestational age) were followed prospectively from
      birth, and studied with magnetic resonance imaging, 3-dimensional magnetic
      resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in
      life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks).
      We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to
      choline ratios, average diffusivity, and white matter fractional anisotropy (FA)
      from up to 7 white and 4 subcortical gray matter regions of interest. Procedural
      pain was quantified as the number of skin-breaking events from birth to term or
      scan 2. Data were analyzed using generalized estimating equation modeling
      adjusting for clinical confounders such as illness severity, morphine exposure,
      brain injury, and surgery. RESULTS: After comprehensively adjusting for multiple
      clinical factors, greater neonatal procedural pain was associated with reduced
      white matter FA (beta=-0.0002, p=0.028) and reduced subcortical gray matter
      NAA/choline (beta=-0.0006, p=0.004). Reduced FA was predicted by early pain
      (before scan 1), whereas lower NAA/choline was predicted by pain exposure
      throughout the neonatal course, suggesting a primary and early effect on
      subcortical structures with secondary white matter changes. INTERPRETATION: Early
      procedural pain in very preterm infants may contribute to impaired brain
      development.

PMID- 22374883
TI  - Limiting cell aggregation during mesenchymal stem cell expansion on
      microcarriers.
AB  - Mesenchymal stem cells (MSC) are known to be a valuable cell source for tissue
      engineering and regenerative medicine. However, one of the main limiting steps in
      their clinical use is the amplification step. MSC expansion on microcarriers has
      emerged during the last few years, fulfilling the lack of classical T-flasks
      expansion. Even if the therapeutic potential of MSC as aggregates has been
      recently highlighted, cell aggregation during expansion has to be avoided. Thus,
      MSC culture on microcarriers has still to be improved, notably concerning cell
      aggregation prevention. The aim of this study was to limit cell aggregation
      during MSC expansion on Cytodex-1(r), by evaluating the impact of several culture
      parameters. First, MSC cultures were performed at different agitation rates (0,
      25, and 75 rpm) and different initial cell densities (25 and 50*10(6) cell g(-1)
      Cytodex-1(r)). Then, the MSC aggregates were put into contact with additional
      available surfaces (T-flask, fresh and used Cytodex-1(r)) at different times
      (before and after cell aggregation). The results showed that cell aggregation was
      partly induced by agitation and prevented in static cultures. Moreover, cell
      aggregation was dependent on cell density and correlated with a decrease in the
      total cell number. It was however shown that the aggregated organization could be
      dissociated when in contact with additional surfaces such as T-flasks or fresh
      Cytodex-1(r) carriers. Finally, cell aggregation could be successfully limited in
      spinner flask by adding fresh Cytodex-1(r) carriers before its onset. Those
      results indicated that MSC expansion on agitated Cytodex-1(r) microcarriers could
      be performed without cell aggregation, avoiding a decrease in total cell number.

PMID- 22374885
TI  - Balloon dilation of the eustachian tube in a cadaver model: technical
      considerations, learning curve, and potential barriers.
AB  - OBJECTIVES/HYPOTHESIS: The surgical management options for eustachian tube
      dysfunction have historically been limited. The goal of the current study was to
      evaluate the technical considerations, learning curve, and potential barriers for
      balloon dilation of the eustachian tube (BDET) as an alternative treatment
      modality. STUDY DESIGN: Prospective preclinical trial of BDET in a cadaver model.
      METHODS: A novel balloon catheter device was used for eustachian tube dilation.
      Twenty-four BDET procedures were performed by three independent rhinologists with
      no prior experience with the procedure (eight procedures per surgeon). The
      duration and number of attempts of the individual steps and overall procedure
      were recorded. Endoscopic examination of the eustachian tube was performed after
      each procedure, and the surgeon was asked to rate the subjective difficulty on a
      five-point scale. RESULTS: Successful completion of the procedure occurred in
      each case. The overall mean duration of the procedure was 284 seconds, and a mean
      number of 1.15 attempts were necessary to perform the individual steps. The mean
      subjective procedure difficulty was noted as somewhat easy. Statistically shorter
      duration and subjectively easier procedure were noted in the second compared to
      the first half of the series, indicating a favorable learning curve. Linear
      fissuring within the eustachian tube lumen without submucosal disruption (nine
      procedures, 37%) and with submucosal disruption (five procedures, 21%) were
      noted. The significance of these physical findings is unclear. CONCLUSIONS:
      Preclinical testing of BDET is associated with favorable duration, learning
      curve, and overall ease of completion. Clinical trials are necessary to evaluate
      safety and efficacy.

PMID- 22374884
TI  - The association of psychotropic medication use with the cognitive, functional,
      and neuropsychiatric trajectory of Alzheimer's disease.
AB  - OBJECTIVE: The use of psychotropic medications in Alzheimer's disease (AD) has
      been associated with both deleterious and potentially beneficial outcomes. We
      examined the longitudinal association of psychotropic medication use with
      cognitive, functional, and neuropsychiatric symptom (NPS) trajectories among
      community-ascertained incident AD cases from the Cache County Dementia
      Progression Study. METHODS: A total of 230 participants were followed for a mean
      of 3.7 years. Persistency index (PI) was calculated for all antidepressants,
      selective serotonin reuptake inhibitors (SSRIs), antipsychotics (atypical and
      typical), and benzodiazepines as the proportion of observed time of medication
      exposure. Mixed-effects models were used to examine the association between PI
      for each medication class and Mini-Mental State Exam (MMSE), Clinical Dementia
      Rating Sum of Boxes (CDR-Sum), and Neuropsychiatric Inventory - Total (NPI-Total)
      trajectories, controlling for appropriate demographic and clinical covariates.
      RESULTS: At baseline, psychotropic medication use was associated with greater
      severity of dementia and poorer medical status. Higher PI for all medication
      classes was associated with a more rapid decline in MMSE. For antidepressant,
      SSRI, benzodiazepine, and typical antipsychotic use, a higher PI was associated
      with a more rapid increase in CDR-Sum. For SSRIs, antipsychotics, and typical
      antipsychotics, a higher PI was associated with more rapid increase in NPI-Total.
      CONCLUSIONS: Psychotropic medication use was associated with more rapid cognitive
      and functional decline in AD, and not with improved NPS. Clinicians may tend to
      prescribe psychotropic medications to AD patients at risk of poorer outcomes, but
      one cannot rule out the possibility of poorer outcomes being caused by
      psychotropic medications.

PMID- 22374886
TI  - A chemo-mechanical tweezer for single-molecular characterization of soft
      materials.
AB  - A new atomic force microscopy (AFM)-based chemo-mechanical tweezer has been
      developed that can measure mechanical properties of individual macromolecules in
      supramolecular assembly and reveal positions of azide-containing polymers. A key
      feature of the new technology is the use of an AFM tip densely modified with 4
      dibenzocyclooctynols (chemo-mechanical tweezer) that can react with multiple
      azide containing macromolecules of micelles to give triazole "clicked" compounds,
      which during retracting phases of AFM imaging are removed from the macromolecular
      assembly thereby providing a surface topographical image and positions of azide
      containing polymers. The force-distance curves gave mechanical properties of
      removal of individual molecules from a supramolecular assembly. The new chemo
      mechanical tweezer will make it possible to characterize molecular details of
      macromolecular assemblies thereby offering new avenues to tailor properties of
      such assemblies.

PMID- 22374888
TI  - The clinical application and efficacy of sodium hyaluronate
      carboxymethylcellulose during tympanomastoid surgery.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the anti-adhesive and anti-inflammatory
      effects of sodium hyaluronate-carboxymethylcellulose (HA-CMC) on postoperative
      hearing improvement and complications during tympanomastoid surgery. STUDY
      DESIGN: Prospective controlled clinical trial. METHODS: We evaluated 287 patients
      who underwent type I tympanoplasty, with or without canal wall up mastoidectomy,
      between January 2007 and June 2010. Postoperative hearing and complications were
      compared in the 143 patients who received Gelfoam soaked with HA-CMC during
      myringoplasty and the 144 patients who received Gelfoam only. RESULTS: There were
      no significant between-group differences in sex, age, and preoperative hearing
      status. However, average postoperative air-bone gap (13.7 +/- 8.5 dB vs. 17.2 +/-
      9.9 dB) and the number of air-bone gaps smaller than 10 dB (40.6% vs. 24.3%) were
      significantly improved in the HA-CMC compared with the control group. In
      addition, the rates of re-otorrhea, reperforation of the tympanic membrane (TM),
      postoperative TM adhesion, and reoperation were lower in the HA-CMC than in the
      control group without significances. CONCLUSIONS: These findings suggest that
      combined application of Gelfoam with HA-CMC may be beneficial in patients
      undergoing tympanomastoid surgery.

PMID- 22374889
TI  - Mechanism of lithium storage in MoS2 and the feasibility of using Li2S/Mo
      nanocomposites as cathode materials for lithium-sulfur batteries.
AB  - The most-popular strategy to improve the cycling stability and rate performance
      of the sulfur electrode in lithium-sulfur (Li-S) batteries is to astrict the
      sulfur in a conducting medium by using complicated chemical/physical processing.
      Lithium sulfide (Li(2)S) has been proposed as an alternative electrode material
      to sulfur. However, for its application, it must meet challenges such as high
      instability in air together with all of the drawbacks of a sulfur-containing
      electrode. Herein, we report the feasibility of using Li(2)S, which was obtained
      by electrochemical conversion of commercial molybdenum disulfide (MoS(2)) into
      Li(2)S and metallic molybdenium (Mo) at low voltages, as a high-performance
      active material in Li-S batteries. Metallic Mo prevented the dissolution of
      lithium polysulfides into the electrolyte and enhanced the conductivity of the
      sulfide electrode. Therefore, the in situ electrochemically prepared Li(2)S/Mo
      composite exhibited both high cycling stability and high sulfur utilization.

PMID- 22374887
TI  - Mitochondrial electron transport chain complex dysfunction in the colonic mucosa
      in ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is characterized by an energy deficiency
      state of the colonic epithelium. This study evaluated mitochondrial electron
      transport chain (ETC) complex activity in normal and disease mucosa in patients
      with UC. Alterations in ETC complexes were also investigated in experimental
      colitis in mice. METHODS: Biopsies were obtained from macroscopically normal and
      diseased colonic mucosa of 43 patients with UC and 35 controls undergoing
      screening colonoscopy and ETC complex activity was assayed biochemically. ETC
      complex activities were also assayed in colonic epithelial cells isolated from
      Swiss albino mice with dextran sodium sulfate (DSS)-induced colitis at various
      stages of induction of colitis. Mucosal nitrite levels and protein carbonyl
      content were determined. RESULTS: The activity of Complex II was significantly
      decreased in colonic biopsies from UC patients compared with controls, while
      activities of other mitochondrial complex were normal. Complex II activity was
      equally decreased in diseased and normal mucosa in UC; the degree of reduction
      did not correlate with clinical, endoscopic, or histological grading of disease
      activity. In DSS-fed mice, a reduction in activity of Complex IV and Complex II
      was observed. Activity of other complex was not affected. Administration of
      aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, attenuated
      all parameters of colitis as well as the reductions in Complex IV and Complex II
      activity. CONCLUSIONS: Reduction in Complex II activity appears to be a specific
      change in UC, present in quiescent and active disease. Mitochondrial complex
      dysfunction occurs in DSS colitis in mice and appears to be mediated by nitric
      oxide.

PMID- 22374890
TI  - Robotic nerve-sparing radical parametrectomy: feasibility and technique.
AB  - BACKGROUND: The objective of this research was to evaluate the feasibility of
      robotic nerve-sparing radical parametrectomy for cervical cancer after simple
      hysterectomy. METHODS: A 41 year-old patient was diagnosed with invasive cervical
      adenocarcinoma after simple hysterectomy. Hysterectomy margins were negative. A
      robotic nerve-sparing radical parametrectomy was offered and performed 5 weeks
      later. RESULTS: Total operating time was 330 min, blood loss was 145 ml and
      length of hospitalization 2 days. Pathology revealed no residual tumour. Normal
      bladder function resumed on postoperative day 9. At a follow-up of 16 months, the
      patient remains with no evidence of disease and with normal bladder and bowel
      function. CONCLUSIONS: Robotic nerve-sparing radical parametrectomy is safe and
      feasible and can be offered to patients with indications for radical
      parametrectomy.

PMID- 22374892
TI  - DNA-directed three-dimensional protein organization.
AB  - All bound together: self-assembled symmetric DNA polyhedra were used to organize
      proteins in 3D space. Biotin moieties were incorporated into the self-assembled
      symmetric DNA polyhedra. Upon incubation with streptavidin (STV) protein, an STV
      protein became bound to each polyhedral face, thus resulting in well-structured
      DNA polyhedra/STV complexes. This strategy was also applied to different 3D DNA
      nanostructures and different proteins.

PMID- 22374891
TI  - Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G
      induced damage in mouse brain.
AB  - OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of
      the central nervous system associated with pathogenic autoantibodies against the
      astrocyte water channel protein aquaporin-4 (AQP4). The presence of neutrophils
      is a characteristic feature in NMO lesions in humans. Neutrophils are not
      generally found in multiple sclerosis lesions. We evaluated the role of
      neutrophils in a mouse NMO model. METHODS: NMO lesions were produced in mice by
      intracerebral injection of immunoglobulin G (IgG) isolated from NMO patient serum
      and human complement. We previously reported that this mouse model produces the
      characteristic histological features of NMO, including perivascular complement
      activation, inflammatory cell infiltration, and loss of myelin, AQP4, and glial
      fibrillary acidic protein. Lesions are absent when AQP4 null mice are used or
      when IgG from non-NMO patients is injected. RESULTS: We found remarkably reduced
      neuroinflammation, myelin loss, and AQP4 loss in brains of neutropenic mice at 24
      hours and 7 days, and increased severity of NMO lesions in mice made neutrophilic
      by granulocyte colony stimulating factor. NMO lesions were greatly reduced by
      intracerebral administration of the neutrophil protease inhibitors Sivelestat and
      cathepsin G inhibitor I or by intraperitoneal injection of Sivelestat alone.
      Immunostaining of human NMO lesions for neutrophil elastase revealed many
      degranulating perivascular neutrophils, with no equivalent perivascular
      neutrophils in human multiple sclerosis lesions. INTERPRETATION: Our data
      implicate a central role of neutrophils in the pathogenesis of early NMO lesions
      and suggest the potential utility of neutrophil protease inhibitors such as
      Sivelestat in NMO therapy.

PMID- 22374893
TI  - ESR adaptation for age--a forgotten pearl.

PMID- 22374894
TI  - A useful diagnostic and prognostic tool for acute appendicitis and acute
      pancreatitis.

PMID- 22374895
TI  - Normal values cannot rule out myeloma.

PMID- 22374896
TI  - ESR can be normal in giant cell arteritis and polymyalgia rheumatica.

PMID- 22374898
TI  - Any UK based legislation could be a double edged sword.

PMID- 22374899
TI  - Legislation is better than education in achieving smoke-free vehicles for
      children.

PMID- 22374900
TI  - Image guided diagnosis and treatment to prevent incontinence after radical
      prostatectomy.

PMID- 22374901
TI  - A narrow definition of performance perhaps?

PMID- 22374903
TI  - Deterioration in colour perception with age might be key.

PMID- 22374904
TI  - Utility of GLP-1R agonists in diabetes requires long term study.

PMID- 22374905
TI  - GLP-1R agonists are not a quick fix for weight loss.

PMID- 22374907
TI  - Drug firms call for changes to German law that limits drug prices.

PMID- 22374908
TI  - Competition improves health services, think tank says.

PMID- 22374909
TI  - Wideband acoustic transfer functions predict middle-ear effusion.
AB  - OBJECTIVES/HYPOTHESIS: Compare the accuracy of wideband acoustic transfer
      functions (WATFs) measured in the ear canal at ambient pressure to methods
      currently recommended by clinical guidelines for predicting middle-ear effusion
      (MEE). STUDY DESIGN: Cross-sectional validating diagnostic study among young
      children with and without MEE to investigate the ability of WATFs to predict MEE.
      METHODS: WATF measures were obtained in an MEE group of 44 children (53 ears;
      median age, 1.3 years) scheduled for middle-ear ventilation tube placement and a
      normal age-matched control group of 44 children (59 ears; median age, 1.2 years)
      with normal pneumatic otoscopic findings and no history of ear disease or middle
      ear surgery. An otolaryngologist judged whether MEE was present or absent and
      rated tympanic-membrane (TM) mobility via pneumatic otoscopy. A likelihood-ratio
      classifier reduced WATF data (absorbance, admittance magnitude and phase) from
      0.25 to 8 kHz to a single predictor of MEE status. Absorbance was compared to
      pneumatic otoscopy classifications of TM mobility. RESULTS: Absorbance was
      reduced in ears with MEE compared to ears from the control group. Absorbance and
      admittance magnitude were the best single WATF predictors of MEE, but a predictor
      combining absorbance, admittance magnitude, and phase was the most accurate.
      Absorbance varied systematically with TM mobility based on data from pneumatic
      otoscopy. CONCLUSIONS: Results showed that absorbance is sensitive to middle-ear
      stiffness and MEE, and WATF predictions of MEE in young children are as accurate
      as those reported for methods recommended by the clinical guidelines.

PMID- 22374911
TI  - High-pressure synthesis and structural investigation of H3P8O8N9: a new
      phosphorus(V) oxonitride imide with an interrupted framework structure.
AB  - The first crystalline phosphorus oxonitride imide H(3)P(8)O(8)N(9)
      (=P(8)O(8)N(6)(NH)(3)) has been synthesized under high-pressure and high
      temperature conditions. To this end, a new, highly reactive phosphorus oxonitride
      imide precursor compound was prepared and treated at 12 GPa and 750  degrees C by
      using a multianvil assembly. H(3)P(8)O(8)N(9) was obtained as a colorless,
      microcrystalline solid. The crystal structure of H(3)P(8)O(8)N(9) was solved ab
      initio by powder X-ray diffraction analysis, applying the charge-flipping
      algorithm, and refined by the Rietveld method (C2/c (no. 15), a=1352.11(7),
      b=479.83(3), c=1820.42(9) pm, beta=96.955(4) degrees , Z=4). H(3)P(8)O(8)N(9)
      exhibits a highly condensed (kappa=0.47), 3D, but interrupted network that is
      composed of all-side vertex-sharing (Q(4)) and only threefold-linking (Q(3))
      P(O,N)(4) tetrahedra in a Q(4)/Q(3) ratio of 3:1. The structure, which includes 4
      ring assemblies as the smallest ring size, can be subdivided into alternating
      open-branched zweier double layers {oB,2(2)(infinity)}[(2)P(3)(O,N)(7)] and
      layers containing pairwise-linked Q(3) tetrahedra parallel (001). Information on
      the hydrogen atoms in H(3)P(8)O(8)N(9) was obtained by 1D (1)H MAS, 2D homo- and
      heteronuclear (together with (31)P) correlation NMR spectroscopy, and a (1)H spin
      diffusion experiment with a hard-pulse sequence designed for selective excitation
      of a single peak. Two hydrogen sites with a multiplicity ratio of 2:1 were
      identified and thus the formula of H(3)P(8)O(8)N(9) was unambiguously determined.
      The protons were assigned to Wyckoff positions 8f and 4e, the latter located
      within the Q(3) tetrahedra layers.

PMID- 22374910
TI  - Formyl-coenzyme A (CoA):oxalate CoA-transferase from the acidophile Acetobacter
      aceti has a distinctive electrostatic surface and inherent acid stability.
AB  - Bacterial formyl-CoA:oxalate CoA-transferase (FCOCT) and oxalyl-CoA decarboxylase
      work in tandem to perform a proton-consuming decarboxylation that has been
      suggested to have a role in generalized acid resistance. FCOCT is the product of
      uctB in the acidophilic acetic acid bacterium Acetobacter aceti. As expected for
      an acid-resistance factor, UctB remains folded at the low pH values encountered
      in the A. aceti cytoplasm. A comparison of crystal structures of FCOCTs and
      related proteins revealed few features in UctB that would distinguish it from
      nonacidophilic proteins and thereby account for its acid stability properties,
      other than a strikingly featureless electrostatic surface. The apparently neutral
      surface is a result of a "speckled" charge decoration, in which charged surface
      residues are surrounded by compensating charges but do not form salt bridges. A
      quantitative comparison among orthologs identified a pattern of residue
      substitution in UctB that may be a consequence of selection for protein stability
      by constant exposure to acetic acid. We suggest that this surface charge pattern,
      which is a distinctive feature of A. aceti proteins, creates a stabilizing
      electrostatic network without stiffening the protein or compromising protein
      solvent interactions.

PMID- 22374912
TI  - Who worries most? Worry prevalence and patterns across the lifespan.
AB  - OBJECTIVE: To examine the age-related worry patterns in a population-based sample
      of self-reported worriers. METHODS: The National Survey of Mental Health and Well
      Being is a multistage stratified epidemiologic survey of mental health conducted
      in Australia in 2007. Participants were surveyed using the Composite
      International Diagnostic Interview. All participants who reported a period of
      pervasive worry were included in this study (N = 3735, 16-85 years of age, 61%
      female). RESULTS: Compared with younger adults (16-29 years of age; N = 860),
      older adults (65-85 years of age; N = 639) reported fewer worries [odds ratio
      (OR) = 0.36, p < 0.01] and a lower likelihood of worrying about interpersonal
      relations (OR = 0.66, p < 0.01), health (OR = 0.65, p < 0.05), work (OR = 0.39, p
      < 0.01), and miscellaneous topics (OR = 0.57, p < 0.01), but a higher likelihood
      of worrying about the health and welfare of loved ones (OR = 2.46, p < 0.01)
      after adjusting for socio-demographic and clinical factors. Similar patterns were
      seen in older persons with and without a lifetime history of generalized anxiety
      disorder as diagnosed by the Diagnostic and Statistical Manual of Mental
      Disorders. CONCLUSIONS: The findings indicated an overall decrease in worry count
      with advancing age, as well as a developmental distribution of worry content, and
      a quantitative but not qualitative distinction between normal and pathological
      worriers. Overall, these findings might contribute to the understanding of worry
      processes and the phenomenology of generalized anxiety disorder in older cohorts.

PMID- 22374913
TI  - Geographic distributions of microscopic colitis and inflammatory bowel disease in
      the United States.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by
      similar geographic distributions. We used a large database of pathology reports
      to analyze the geographic distribution of microscopic colitis (MC) and compare it
      with those of UC and CD. METHODS: A population of 671,176 individual patients
      with colonic biopsies was studied stratified by gender and state of residence.
      The occurrence of each diagnosis MC, UC, or CD, was expressed as proportional
      rate per 1000 colonoscopies with biopsies from each individual state. RESULTS: UC
      and CD tended to be common in states in the Northeast or North Central regions of
      the U.S. and relatively rare among several southern states. MC appeared to follow
      a somewhat inverse pattern, as it was most common among some states from the
      Southwest (Colorado, New Mexico, Arizona, Nevada) and other states of southern
      latitude, such as Florida, Georgia, California, but relatively uncommon among
      states in the Northeast. The geographic distributions of UC and CD were
      significantly correlated with each other (R = 0.60 and P = 0.0004). No
      significant correlation was observed between MC and UC or CD. CONCLUSIONS: The
      differences in epidemiologic behavior point at a dissimilar set of risk factors
      that shape the occurrence of MC as opposed to UC or CD.

PMID- 22374914
TI  - Effect of gender on the hearing performance of adult cochlear implant patients.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the role of gender on the hearing performance
      of postlingually deafened adult patients with cochlear implants. STUDY DESIGN:
      Individual retrospective cohort study. METHODS: There were 638 postlingually
      deafened adults (280 men and 358 women) selected for a retrospective evaluation
      of their hearing performance with cochlear implants. Both genders underwent the
      same surgical and rehabilitative procedures and benefited from the latest
      technological advances available. There was no significant difference in the age,
      duration of deafness, and preoperative hearing performance between the genders.
      The test battery was composed of the Freiburger Monosyllabic Test, Speech
      Tracking, and the Hochmair-Schulz-Moser (HSM) sentence test in quiet and in 10-dB
      noise. The results of 5 years of follow-up are presented here. RESULTS: Genders
      showed a similar performance in Freiburger Monosyllabic Test and Speech Tracking
      Test. However, in the HSM test in noise, men performed slightly better than women
      in all of the follow-up sessions, which was statistically significant at 2 and 4
      years after implantation. CONCLUSIONS: Although normal-hearing women use more
      predictive cognitive strategies in speech comprehension and are supposed to have
      a more efficient declarative memory system, this may not necessarily lead to a
      better adaptation to the altered auditory information delivered by a cochlear
      implant. Our study showed that in more complex listening situations such as
      speech tests in noise, men tend to perform slightly better than women. Gender may
      have an influence on the hearing performance of postlingually deafened adults
      with cochlear implants.

PMID- 22374915
TI  - Electric nanocar equipped with four-wheel drive gets taken for its first spin.

PMID- 22374916
TI  - The thermodynamics of translesion DNA synthesis past major adducts of
      enantiomeric analogues of antitumor cisplatin.
AB  - The Pt(II)-coordination complex [PtCl(2)(DAB)] (DAB=2,3-diaminobutane) belongs to
      a class of cytotoxic cisplatin analogues that contain chiral diamine ligands.
      Enantiomeric pairs of these compounds have attracted particular interest because
      they have different effects on different DNA conformations, which, in turn,
      influences the binding of damaged-DNA-processing enzymes that control downstream
      effects of the adducts, and thus exhibit different biological activities of the
      enantiomers. Herein, we studied the translesion synthesis across the major 1,2
      d(GG) intrastrand cross-link formed by the R,R and S,S enantiomers of
      [Pt(DAB)](2+) in the TGGT sequence by using the enzyme that catalyzes the
      polymerization of deoxyribonucleotides into a DNA strand. We also employed
      differential scanning calorimetry (DSC) to measure the thermodynamic changes
      associated with replication-bypass past 1,2-d(GG) adducts of the [Pt(DAB)](2+)
      enantiomers. In the sequence TGGT, the 1,2-d(GG) intrastrand cross-links that
      were formed by the enantiomeric pairs of [Pt(DAB)](2+) inhibited DNA
      polymerization in a chirality-dependent manner. The thermodynamic data helped to
      understand the effect of the alterations in thermodynamic stability of DNA caused
      by the Pt-d(GG) adducts upon DNA polymerization across these lesions. Moreover,
      these data can possibly explain the influence of these alterations on the ability
      of many DNA polymerases to bypass adducts of antitumor platinum drugs. These
      results also highlighted the usefulness of DSC in evaluating the impact of DNA
      adducts of platinum-coordinated compounds on the processing of these lesions by
      damaged-DNA processing-enzymes.

PMID- 22374917
TI  - Generation of Fbn1 conditional null mice implicates the extracellular
      microfibrils in osteoprogenitor recruitment.
AB  - Loss-of-function experiments in mice have yielded invaluable mechanistic insights
      into the pathogenesis of Marfan syndrome (MFS) and implicitly, into the multiple
      roles fibrillin-1 microfibrils play in the developing and adult organism.
      Unfortunately, neonatal death from aortic complications of mice lacking fibrillin
      1 (Fbn1(-/-) mice) has limited the scope of these studies. Here, we report the
      creation of a conditional mutant allele (Fbn1(fneo) ) that contains loxP sites
      bordering exon1 of Fbn1 and an frt-flanked neo expression cassette downstream of
      it. Fbn1(fneo/+) mice were crossed with FLPeR mice and the resulting Fbn1(Lox/+)
      progeny were crossed with Fbn1(+/-) ;CMV-Cre mice to generate Fbn1(CMV-/-) mice,
      which were found to phenocopy the vascular abnormalities of Fbn1(-/-) mice.
      Furthermore, mating Fbn1(Lox/+) mice with Prx1-Cre or Osx-Cre mice revealed an
      unappreciated role of fibrillin-1 microfibrils in restricting osteoprogenitor
      cell recruitment. Fbn1(Lox/+) mice are, therefore, an informative genetic
      resource to further dissect MFS pathogenesis and the role of extracellular
      fibrillin-1 assemblies in organ development and homeostasis.

PMID- 22374918
TI  - Cross-coupling reactions of organosilicon compounds in the stereocontrolled
      synthesis of retinoids.
AB  - This paper presents a full account of the use of Hiyama cross-coupling reactions
      in a highly convergent approach to retinoids in which the key step is
      construction of the central C10-C11 bond. Representatives of two families of
      oxygen-activated dienyl silanes (ethoxysilanes and silanols) and of all reported
      families of "safety-catch" silanols (siletanes, silyl hydrides, allyl-, benzyl-,
      aryl-, 2-pyridyl- and 2-thienylsilanes) were regio- and stereoselectively
      prepared and stereospecifically coupled to an appropriate electrophile by
      treatment with a palladium catalyst and a nucleophilic activator. Both all-trans
      and 11-cis-retinoids, and their chain-demethylated analogues, were obtained in
      good yields regardless of the geometry (E/Z) and of the steric congestion in each
      fragment. This comprehensive study conclusively establishes the Hiyama cross
      coupling reaction, with its mild reaction conditions and stable, easily prepared,
      ecologically advantageous silicon-based coupling partners, as the most effective
      route to retinoids reported to date.

PMID- 22374919
TI  - Normative diameters and effects of aging on the cochlear and facial nerves in
      normal-hearing Korean ears using 3.0-tesla magnetic resonance imaging.
AB  - OBJECTIVES/HYPOTHESIS: To assess the normative size of the cochlear nerve (CN)
      and facial nerve (FN) in normal-hearing ears and to determine whether nerve size
      varies with age. STUDY DESIGN: Cross-sectional. METHODS: We included 169 ears
      with normal hearing between 2005 and 2010. The height, width, and cross-sectional
      area (CSA) of the CN and FN in the middle of the internal auditory canal were
      measured on oblique sagittal images of 3.0-T magnetic resonance imaging. Results
      were compared by age. Young subjects were divided into three age groups, 0-5, 6
      10, and 11-15 years. Subjects over age 40 years were divided into groups at 10
      year intervals. RESULTS: Mean age was 32.6 years (range, 0.75-79 years). We found
      that the CN had significantly greater vertical (1.10 +/- 0.21 mm vs. 0.95 +/-
      0.21 mm) and horizontal (1.11 +/- 0.20 mm vs. 1.03 +/- 0.22 mm) diameters than
      the FN. The CSA of the CN was larger than that of the FN (0.98 +/- 0.33 mm(2) 
      vs. 0.79 +/- 0.31 mm(2) ). Except for the CN vertical diameter, there were no
      significant differences between right and left ears. Sex did not affect the nerve
      size. Although the CN was not affected by age, the FN vertical diameter and CSA
      of children <5 years were significantly smaller than those of children aged >5
      years. The size of the two nerves did not differ among groups over age 40 years.
      CONCLUSIONS: The CN is not affected by age in normal-hearing ears. The FN
      vertical diameter and CSA of children <5 years are smaller than those of older
      children.

PMID- 22374920
TI  - Effect of fissure integrity on lung volume reduction using a polymer sealant in
      advanced emphysema.
AB  - RATIONALE: Interlobar fissure integrity has previously correlated with
      responsiveness to endobronchial lung volume reduction therapy in patients with
      advanced emphysema. OBJECTIVE: This report summarises the effect of interlobar
      fissure integrity on responses to treatment with a novel endoscopic tissue
      sealant (AeriSeal emphysematous lung sealant (ELS)) that collapses hyperinflated
      lung. METHODS: Fissure status, lung volumes, tissue density and disease
      heterogeneity were assessed radiographically in 28 patients (age 63.4+/-6.1
      years, 20 men) with advanced upper lobe predominant emphysema (density=888.0+/
      18.2 HU; upper lobe tissue density < -950 = 2.62+/-1.74). Post-treatment changes
      in lobar volume, pulmonary function, exercise capacity, symptoms and quality of
      life were compared in patients with complete fissures (CFs) and incomplete
      fissures (ICFs). RESULTS: ELS therapy reduced lung volumes independent of
      interlobar fissure integrity. In patients with upper lobe emphysema and CFs,
      lobar volume reduction was 214+/-127 ml/treatment compared with 256+/-175
      ml/treatment in those with ICFs (p=0.453). Reductions in gas trapping and
      improvements in spirometry, functional capacity and quality of life were similar
      in patients with CFs and ICFs. Stepwise multiple regression modelling confirmed
      that fissure integrity did not contribute to post-treatment changes in forced
      expiratory volume in 1 s, residual volume/total lung capacity ratio or lobar
      volume measured by CT analysis. CONCLUSIONS: Interlobar fissure integrity, an
      important determinant of responsiveness to endobronchial lung volume reduction
      therapy in prior studies, had minimal impact on physiological and functional
      responses to ELS therapy in patients with severe upper lobe predominant
      emphysema. CLINICAL TRIAL REGISTRATION NUMBER: Registration numbers for trials
      contributing to datasets in this report: NCT00884962, NCT01051258 and
      NCT01181466.

PMID- 22374921
TI  - Serotype prevalence in adults hospitalised with pneumococcal non-invasive
      community-acquired pneumonia.
AB  - BACKGROUND: The distribution of pneumococcal serotypes implicated in non-invasive
      community-acquired pneumonia (CAP) in adults is currently unknown. METHODS: A
      prospective observational cohort study was conducted over 2 years in a large U.K.
      teaching hospital trust. Urine samples, in addition to routine blood and sputum
      samples, were obtained from consecutive adults admitted to the hospital with CAP.
      Pneumococcal serotype was determined from urine samples using a validated
      multiplex immunoassay which detects 14 serotypes. RESULTS: Of 920 patients with
      CAP, 366 had pneumococcal CAP; 242 had a serotype determined. Thirty-day
      mortality was 10% for all-cause CAP and 9.6% for pneumococcal CAP. Annual
      incidence of pneumococcal CAP was 36.5 per 100,000, increasing from 12.1 to 274.1
      per 100,000 for ages 16-44 years and >=85 years, respectively. The most prevalent
      serotypes were 14, 1, 8, 3 and 19A. Less invasive serotypes were significantly
      associated with increasing age (OR per increasing age group: 1.5, 95% CI 1.2 to
      1.9, p<0.001) and co-morbidity (OR per increasing Charlson index group: 1.4, 95%
      CI 1.0 to 2.0, p=0.036), and with higher 30-day mortality (OR adjusted for age
      and co-morbidity: 5.5, 95% CI 1.2 to 25.3, p=0.028) compared with highly invasive
      serotypes. The proportion of patients in whom serotypes contained within the
      seven-valent childhood pneumococcal conjugate vaccine was identified increased
      with age (15.6% for patients aged 16-44 years, 41.0% for patients aged >=85
      years; p<0.05). CONCLUSIONS: In adult invasive and non-invasive pneumococcal CAP,
      the most common serotypes implicated were 14, 1, 8, 3 and 19A. Age and co
      morbidity were associated with the distribution of serotypes identified.

PMID- 22374923
TI  - Systemic elastin degradation in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Development of emphysema and vascular stiffness in chronic
      obstructive pulmonary disease (COPD) may be due to a common mechanism of
      susceptibility to pulmonary and systemic elastin degradation. OBJECTIVES: To
      investigate whether patients with COPD have evidence of systemic elastin
      degradation in the skin. METHODS: The authors measured cutaneous elastin
      degradation using immunohistochemistry (percentage area of elastin fibres) in sun
      exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with
      COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative
      PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of
      metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9
      were performed on homogenised skin. Arterial stiffness and emphysema severity
      were measured using carotid-femoral pulse wave velocity and quantitative CT
      scanning. RESULTS: Skin elastin degradation was greater in exposed and non
      exposed skin of patients with COPD compared with controls (exposed, mean (SD);
      43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%,
      p=0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was
      increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and
      was also associated with increased skin elastin degradation (r=0.62, p<0.001 and
      r=0.47, p=0.01, respectively). In the entire cohort of ex-smokers, cutaneous
      elastin degradation was associated with emphysema severity, FEV(1) and pulse wave
      velocity. CONCLUSIONS: Patients with COPD have increased skin elastin degradation
      compared with controls, which is related to emphysema severity and arterial
      stiffness. Systemic elastin degradation due to increased proteolytic activity may
      represent a novel shared mechanism for the pulmonary, vascular and cutaneous
      features of COPD.

PMID- 22374924
TI  - Collateral ventilation and selection of techniques for bronchoscopic lung volume
      reduction.

PMID- 22374925
TI  - Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in
      ulcerative colitis.
AB  - BACKGROUND: Reliable biomarkers for monitoring disease activity have not been
      clinically established in ulcerative colitis (UC). This study aimed to
      investigate whether levels of serum leucine-rich alpha-2 glycoprotein (LRG),
      identified recently as a potential disease activity marker in Crohn's disease and
      rheumatoid arthritis, correlate with disease activity in UC. METHODS: Serum LRG
      concentrations were determined by enzyme-linked immunosorbent assay (ELISA) in
      patients with UC and healthy controls (HC) and were evaluated for correlation
      with disease activity. Expression of LRG in inflamed colonic tissues from
      patients with UC was analyzed by western blotting and immunohistochemistry.
      Interleukin (IL)-6-independent induction of LRG was investigated using IL-6
      deficient mice by lipopolysaccharide (LPS)-mediated acute inflammation and
      dextran sodium sulfate (DSS)-induced colitis. RESULTS: Serum LRG concentrations
      were significantly elevated in active UC patients compared with patients in
      remission (P < 0.0001) and HC (P < 0.0001) and were correlated with disease
      activity in UC better than C-reactive protein (CRP). Expression of LRG was
      increased in inflamed colonic tissues in UC. Tumor necrosis factor alpha (TNF
      alpha), IL-6, and IL-22, serum levels of which were elevated in patients with
      active UC, could induce LRG expression in COLO205 cells. Serum LRG levels were
      increased in IL-6-deficient mice with LPS-mediated acute inflammation and DSS
      induced colitis. CONCLUSIONS: Serum LRG concentrations correlate well with
      disease activity in UC. LRG induction is robust in inflamed colons and is likely
      to involve an IL-6-independent pathway. Serum LRG is thus a novel serum biomarker
      for monitoring disease activity in UC and is a promising surrogate for CRP.

PMID- 22374926
TI  - Watchdog group says "massive lobbying effort" by medical device industry
      threatens public health.

PMID- 22374927
TI  - Royal College of Physicians votes to ballot members on whether to demand health
      bill's withdrawal.

PMID- 22374928
TI  - Happiness is a U shaped curve, highest in the teens and 70s, shows survey.

PMID- 22374929
TI  - Hospitals need to change to ensure older people are treated with dignity, says
      commission.

PMID- 22374930
TI  - UK exceeds target on mortality from elective repair of abdominal aneurysm four
      years early.

PMID- 22374931
TI  - Treating negative symptoms of schizophrenia.

PMID- 22374932
TI  - Group art therapy as an adjunctive treatment for people with schizophrenia:
      multicentre pragmatic randomised trial.
AB  - OBJECTIVES: To evaluate the clinical effectiveness of group art therapy for
      people with schizophrenia and to test whether any benefits exceed those of an
      active control treatment. DESIGN: Three arm, rater blinded, pragmatic, randomised
      controlled trial. SETTING: Secondary care services across 15 sites in the United
      Kingdom. PARTICIPANTS: 417 people aged 18 or over, who had a diagnosis of
      schizophrenia and provided written informed consent to take part in the study.
      INTERVENTIONS: Participants, stratified by site, were randomised to 12 months of
      weekly group art therapy plus standard care, 12 months of weekly activity groups
      plus standard care, or standard care alone. Art therapy and activity groups had
      up to eight members and lasted for 90 minutes. In art therapy, members were given
      access to a range of art materials and encouraged to use these to express
      themselves freely. Members of activity groups were offered various activities
      that did not involve use of art or craft materials and were encouraged to
      collectively select those they wanted to pursue. MAIN OUTCOME MEASURES: The
      primary outcomes were global functioning, measured using the global assessment of
      functioning scale, and mental health symptoms, measured using the positive and
      negative syndrome scale, 24 months after randomisation. Main secondary outcomes
      were levels of group attendance, social functioning, and satisfaction with care
      at 12 and 24 months. RESULTS: 417 participants were assigned to either art
      therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary
      outcomes between the three study arms did not differ. The adjusted mean
      difference between art therapy and standard care at 24 months on the global
      assessment of functioning scale was -0.9 (95% confidence interval -3.8 to 2.1),
      and on the positive and negative syndrome scale was 0.7 (-3.1 to 4.6). Secondary
      outcomes did not differ between those referred to art therapy or those referred
      to standard care at 12 or 24 months. CONCLUSIONS: Referring people with
      established schizophrenia to group art therapy as delivered in this trial did not
      improve global functioning, mental health, or other health related outcomes.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN46150447.

PMID- 22374933
TI  - Home drinking in the UK: trends and causes.
AB  - AIMS: To explore the trend in the UK to consume alcohol at home rather than at
      licensed premises. METHODS: A Medline search entering the terms 'home drinking',
      'alcohol' and 'adult' covering the period 2000-2011 yielded 48 articles, of which
      6 met the criteria to be included in the review. Grey literature including survey
      and market research data were reviewed. RESULTS: In the UK, since 1970 there has
      been trend for beer to be consumed at home more often than in licensed premises
      and that the overall trend towards greater home drinking has increased since
      2000. The main reasons given are convenience, cost, safety, autonomy and stress
      relief. There has also been an increase in the practice known as 'pre-loading'
      (drinking before going out). Adults who drink mainly at home report that they are
      aware that they run a risk of higher overall alcohol consumption but tend to play
      down the possibility that increased consumption may lead to longer-term harm.
      CONCLUSION: Home drinking trends may have long-term public health consequences.
      Greater understanding of the drivers of this trend will help policy-makers to
      respond to these societal changes.

PMID- 22374934
TI  - Bi-directional semantic similarity for gene ontology to optimize biological and
      clinical analyses.
AB  - BACKGROUND: Semantic similarity analysis facilitates automated semantic
      explanations of biological and clinical data annotated by biomedical ontologies.
      Gene ontology (GO) has become one of the most important biomedical ontologies
      with a set of controlled vocabularies, providing rich semantic annotations for
      genes and molecular phenotypes for diseases. Current methods for measuring GO
      semantic similarities are limited to considering only the ancestor terms while
      neglecting the descendants. One can find many GO term pairs whose ancestors are
      identical but whose descendants are very different and vice versa. Moreover, the
      lower parts of GO trees are full of terms with more specific semantics. METHODS:
      This study proposed a method of measuring semantic similarities between GO terms
      using the entire GO tree structure, including both the upper (ancestral) and the
      lower (descendant) parts. Comprehensive comparison studies were performed with
      well-known information content-based and graph structure-based semantic
      similarity measures with protein sequence similarities, gene expression-profile
      correlations, protein-protein interactions, and biological pathway analyses.
      CONCLUSION: The proposed bidirectional measure of semantic similarity
      outperformed other graph-based and information content-based methods.

PMID- 22374935
TI  - Portability of an algorithm to identify rheumatoid arthritis in electronic health
      records.
AB  - OBJECTIVES: Electronic health records (EHR) can allow for the generation of large
      cohorts of individuals with given diseases for clinical and genomic research. A
      rate-limiting step is the development of electronic phenotype selection
      algorithms to find such cohorts. This study evaluated the portability of a
      published phenotype algorithm to identify rheumatoid arthritis (RA) patients from
      EHR records at three institutions with different EHR systems. MATERIALS AND
      METHODS: Physicians reviewed charts from three institutions to identify patients
      with RA. Each institution compiled attributes from various sources in the EHR,
      including codified data and clinical narratives, which were searched using one of
      two natural language processing (NLP) systems. The performance of the published
      model was compared with locally retrained models. RESULTS: Applying the
      previously published model from Partners Healthcare to datasets from Northwestern
      and Vanderbilt Universities, the area under the receiver operating characteristic
      curve was found to be 92% for Northwestern and 95% for Vanderbilt, compared with
      97% at Partners. Retraining the model improved the average sensitivity at a
      specificity of 97% to 72% from the original 65%. Both the original logistic
      regression models and locally retrained models were superior to simple billing
      code count thresholds. DISCUSSION: These results show that a previously published
      algorithm for RA is portable to two external hospitals using different EHR
      systems, different NLP systems, and different target NLP vocabularies. Retraining
      the algorithm primarily increased the sensitivity at each site. CONCLUSION:
      Electronic phenotype algorithms allow rapid identification of case populations in
      multiple sites with little retraining.

PMID- 22374936
TI  - Harnessing neuroplasticity for clinical applications.

PMID- 22374937
TI  - 'Moving' a paralysed hand: bimanual coupling effect in patients with anosognosia
      for hemiplegia.
AB  - Selective neurological impairments can shed light on different aspects of motor
      cognition. Brain-damaged patients with anosognosia for hemiplegia deny their
      motor deficit and believe they can still move the paralysed limb. Here we study,
      for the first time, if the anomalous subjective experience that their affected
      hand can still move, may have objective consequences that constrain movement
      execution with the opposite, intact hand. Using a bimanual motor task, in which
      anosognosic patients were asked to simultaneously trace out lines with their
      unaffected hand and circles with their paralysed hand, we found that the
      trajectories of the intact hand were influenced by the requested movement of the
      paralysed hand, with the intact hand tending to assume an oval trajectory
      (bimanual coupling effect). This effect was comparable to that of a group of
      healthy subjects who actually moved both hands. By contrast, brain-damaged
      patients with motor neglect or actual hemiplegia but no anosognosia did not show
      this bimanual constraint. We suggest that anosognosic patients may have intact
      motor intentionality and planning for the plegic hand. Rather than being merely
      an inexplicable confabulation, anosognosia for the plegic hand can produce
      objective constraints on what the intact hand does.

PMID- 22374938
TI  - Lawrence and Kuypers (1968a, b) revisited: copies of the original filmed material
      from their classic papers in Brain.
AB  - This article aims to reintroduce two classic papers on motor control published in
      Brain in 1968, in which Lawrence and Kuypers reported their systematic studies of
      the effects of lesions to the corticospinal system (Lawrence and Kuypers, 1968a),
      and subsequently to the descending brainstem pathways (Lawrence and Kuypers,
      1968b) in the Old World macaque monkey. They showed that the capacity for
      independent movements of the digits was permanently lost after a complete,
      bilateral lesion of the corticospinal system. These studies also revealed that
      the brainstem pathways contribute to fundamentally different aspects of motor
      control, with one set of pathways (the ventromedial system) involved in the
      control of head, trunk and girdle movements, while the other, lateral set of
      fibres control movements of the extremity such as reach and grasp. There is still
      much to learn today from these papers. However, an important part of their
      scientific legacy, the films illustrating the different cases, has long been
      unavailable. Much of this filmed material is now made available again in video
      format accessible on the Brain web site, complete with supplementary notes and
      histological detail. This article summarizes this newly available material for
      these classic papers in Brain.

PMID- 22374939
TI  - Pumpless arterio-venous extracorporeal lung assist compared with veno-venous
      extracorporeal membrane oxygenation during experimental lung injury.
AB  - BACKGROUND: Extracorporeal lung support is effective to prevent hypoxaemia and
      excessive hypercapnia with respiratory acidosis in acute respiratory distress
      syndrome. Miniaturized veno-venous extracorporeal membrane oxygenation (mECMO)
      and arterio-venous pumpless extracorporeal lung assist (pECLA) were compared for
      respiratory and haemodynamic response and extracorporeal gas exchange and device
      characteristics. METHODS: After induction of acute lung injury by repeated lung
      lavage, 16 anaesthetized and mechanically ventilated pigs were randomized to
      mECMO (Medos Hilite/Deltastream) or pECLA (iLA Novalung) for 24 h. RESULTS:
      Improved gas exchange allowed reduced ventilation and plateau pressure in both
      groups. An arterio-venous shunt flow of up to 30% of cardiac output resulted in a
      left cardiac work of 6.8 (2.0) kg m for pECLA compared with 5.0 (1.4) kg m for
      mECMO after 24 h (P<0.05). Both devices provided adequate oxygen delivery to
      organs. The oxygen transfer of pECLA was lower than mECMO due to inflow of
      arterial oxygenated blood [16 (5) compared with 64 (28) ml min(-1) after 24 h,
      P<0.05]. Unexpectedly, the carbon dioxide transfer rate was also lower [58 (28)
      compared with 111 (42) ml min(-1) after 24 h, P<0.05], probably caused by a
      Haldane effect preventing higher transfer rates in combination with lower
      extracorporeal blood flow. CONCLUSIONS: Both devices have the potential to unload
      the lungs from gas transfer sufficiently to facilitate lung-protective
      ventilation. Although technically less complex, oxygen uptake and carbon dioxide
      removal are limited in pECLA, and cardiac work was increased. mECMO overcomes
      these limitations and might provide better cardiopulmonary protection.

PMID- 22374940
TI  - Carnosol, a constituent of Zyflamend, inhibits aryl hydrocarbon receptor-mediated
      activation of CYP1A1 and CYP1B1 transcription and mutagenesis.
AB  - The aryl hydrocarbon receptor (AhR), a ligand-activated member of the basic helix
      loop-helix family of transcription factors, plays a significant role in
      polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis. In the upper
      aerodigestive tract of humans, tobacco smoke, a source of PAHs, activates the AhR
      leading to increased expression of CYP1A1 and CYP1B1, which encode proteins that
      convert PAHs to genotoxic metabolites. Inhibitors of Hsp90 ATPase cause a rapid
      decrease in levels of AhR, an Hsp90 client protein, and thereby block PAH
      mediated induction of CYP1A1 and CYP1B1. The main objective of this study was to
      determine whether Zyflamend, a polyherbal preparation, suppressed PAH-mediated
      induction of CYP1A1 and CYP1B1 and inhibited DNA adduct formation and
      mutagenesis. We also investigated whether carnosol, one of multiple phenolic
      antioxidants in Zyflamend, had similar inhibitory effects. Treatment of cell
      lines derived from oral leukoplakia (MSK-Leuk1) and skin (HaCaT) with
      benzo[a]pyrene (B[a]P), a prototypic PAH, induced CYP1A1 and CYP1B1
      transcription, resulting in enhanced levels of message and protein. Both
      Zyflamend and carnosol suppressed these effects of B[a]P. Notably, both Zyflamend
      and carnosol inhibited Hsp90 ATPase activity and caused a rapid reduction in AhR
      levels. The formation of B[a]P-induced DNA adducts and mutagenesis was also
      inhibited by Zyflamend and carnosol. Collectively, these results show that
      Zyflamend and carnosol inhibit Hsp90 ATPase leading to reduced levels of AhR,
      suppression of B[a]P-mediated induction of CYP1A1 and CYP1B1, and inhibition of
      mutagenesis. Carnosol-mediated inhibition of Hsp90 ATPase activity can help
      explain the chemopreventive activity of herbs such as Rosemary, which contain
      this phenolic antioxidant.

PMID- 22374941
TI  - Labral penetration rate in a consecutive series of 300 hip arthroscopies.
AB  - BACKGROUND: Intraoperative labral injury during the establishment of the first
      portal in hip arthroscopy has been reported to be as high as 20%. PURPOSE: The
      purpose of the study was to prospectively identify the incidence of acetabular
      labral injuries that occurred while using a current technique for the
      establishment of portals during hip arthroscopy. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: Between the years 2008 and 2010, data were prospectively
      collected for all patients undergoing hip arthroscopic surgery. Patients with
      previous labral resection or Tonnis grade greater than 1 were excluded. Patients
      were positioned supine, traction was applied, and portals were established. The
      anterolateral portal was created first by venting the joint with a spinal needle
      and then re-entering the joint with the same needle with the bevel side facing
      the labrum. Next, the midanterior portal was created under vision. A thorough
      examination of the acetabular labrum was conducted arthroscopically through
      multiple viewing portals, and labral injuries related to the establishment of
      portals were identified and noted. RESULTS: A total of 300 patients were included
      in the study; only 2 patients (0.67%) suffered intraoperative labral injuries at
      the study period. One injury occurred during revision arthroscopy, while the
      second involved a hyperplastic labrum in a dysplastic hip. No patient with normal
      hip morphological characteristics undergoing a hip arthroscopy suffered a labral
      tear as a result of portal placement. CONCLUSION: The incidence of iatrogenic
      labral injury during hip arthroscopy can be as low as 0.67% when using the
      described technique.

PMID- 22374943
TI  - Results of meniscus allograft transplantation using bone fixation: 110 cases with
      objective evaluation.
AB  - BACKGROUND: Meniscus allograft transplantation (MAT) has shown efficacy in
      relieving pain and improving knee joint function, but objective evaluation in a
      large number of patients is necessary to verify this effect. HYPOTHESIS: Meniscus
      allograft transplantation relieves pain and improves function of the involved
      knee joint. Objective evaluation provides evidence of allograft integrity. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Of the 115 knees that
      underwent MAT from December 1996 to February 2009, 110 (95.7%) were followed up
      for more than 2 years and were enrolled in this study. Of these, 83 underwent
      lateral MAT, and 27 underwent medial MAT. Clinical outcomes were evaluated using
      the modified Lysholm score and Knee Society pain score. All knees underwent
      postoperative magnetic resonance imaging (MRI) and/or second-look arthroscopy to
      evaluate the integrity and position of the allografts, with allograft status
      classified as satisfactory, fair, or poor. RESULTS: At a mean follow-up of 49.4
      months, clinical improvement was achieved in 104 of the 110 knees (94.5%). Mean
      modified Lysholm score increased from 72.7 preoperatively to 92.3 at final follow
      up (P < .001), and mean preoperative Knee Society pain score increased from 32.5
      to 47.7 (P < .001). Of the 110 knees, 90 were evaluated by postoperative MRI
      alone, 2 by second-look arthroscopy alone, and 18 by both. Magnetic resonance
      imaging showed 12 gross tears and 6 small tears in the allograft. Mean extrusion
      of the allograft was 3.7 mm, and mean relative percentage of extrusion was 42.6%.
      Second-look arthroscopy showed 6 gross tears and 1 small flap tear.
      Classification by clinical outcome, MRI, and second-look arthroscopy graded 90
      allografts (81.8%) as satisfactory, 8 (7.3%) as fair, and 12 (10.9%) as poor.
      CONCLUSION: Meniscus allograft transplantation using bone fixation resulted in
      significant symptomatic and functional improvements. Magnetic resonance imaging
      or second-look arthroscopy was necessary to assess allograft status even after
      favorable clinical outcome. Meniscus allograft transplantation with bone fixation
      is considered effective for symptomatic, totally meniscectomized knees.

PMID- 22374944
TI  - Stability of double-row rotator cuff repair is not adversely affected by scaffold
      interposition between tendon and bone.
AB  - BACKGROUND: Rotator cuff reconstructions may be improved by adding growth
      factors, cells, or other biologic factors into the repair zone. This usually
      requires a biological carrier (scaffold) to be integrated into the construct and
      placed in the area of tendon-to-bone healing. This needs to be done without
      affecting the constructs mechanics. Hypothesis/ PURPOSE: The hypothesis was that
      scaffold placement, as an interposition, has no adverse effects on biomechanical
      properties of double-row rotator cuff repair. The purpose of this study was to
      examine the effect of scaffold interposition on the initial strength of rotator
      cuff repairs. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-five
      fresh-frozen shoulders (mean age: 65.5 +/- 8.9 years) were randomly assigned to 5
      groups. Groups were chosen to represent a broad spectrum of commonly used
      scaffold types: (1) double-row repair without augmentation, (2) double-row repair
      with interposition of a fibrin clot (Viscogel), (3) double-row repair with
      interposition of a collagen scaffold (Mucograft) between tendon and bone, (4)
      double-row repair with interposition of human dermis patch (ArthroFlex) between
      tendon and bone, and (5) double-row repair with human dermis patch (ArthroFlex)
      placed on top of the repair. Cyclic loading to measure displacement was performed
      to 3000 cycles at 1 Hz with an applied 10- to 100-N load. The ultimate load to
      failure was determined at a rate of 31 mm/min. RESULTS: There were no significant
      differences in mean displacement under cyclic loading, slope, or energy absorbed
      to failure between all groups (P = .128, P = .981, P = .105). Ultimate load to
      failure of repairs that used the collagen patch as an interposition (573.3 +/-
      75.6 N) and a dermis patch on top of the reconstruction (575.8 +/- 22.6 N) was
      higher compared with the repair without a scaffold (348.9 +/- 98.8 N; P = .018
      and P = .025). No significant differences were found for repairs with the fibrin
      clot as an interposition (426.9 +/- 103.6 N) and the decellularized dermis patch
      as an interposition (469.9 +/- 148.6 N; P = .73 and P = .35). CONCLUSION:
      Scaffold augmentation did not adversely affect the zero time strength of the
      tested standard double-row rotator cuff repairs. An increased ultimate load to
      failure was observed for 2 of the augmentation methods (collagen patch as an
      interposition and decellularized dermis patch on top of the reconstruction)
      compared with the nonaugmented repairs. CLINICAL RELEVANCE: Scaffolds intended
      for application of growth factors or cellular components in a repair situation
      did not adversely jeopardize the stability of the operative construct.

PMID- 22374942
TI  - Association between previous meniscal surgery and the incidence of chondral
      lesions at revision anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Knees undergoing revision anterior cruciate ligament (ACL)
      reconstruction typically have more intra-articular injuries than do knees
      undergoing primary reconstruction. HYPOTHESIS: Previous partial meniscectomy (PM)
      is associated with a higher rate of chondral lesions at revision ACL
      reconstruction, whereas previous meniscal repair (MR) is not associated with a
      higher rate of chondral lesions at revision ACL reconstruction, compared with
      knees undergoing revision ACL with no previous meniscal surgery. STUDY DESIGN:
      Cohort study (Prevalence); Level of evidence, 2. METHODS: Data from a multicenter
      cohort was reviewed to determine the history of prior meniscal surgery (PM/MR)
      and the presence of grade II/III/IV chondral lesions at revision ACL
      reconstruction. The association between previous meniscal surgery and the
      incidence of chondral lesions was examined. Patient age was included as a
      covariate to determine if surgery type contributes predictive information
      independent of patient age. RESULTS: The cohort included 725 ACL revision
      surgeries. Chondrosis was associated with patient age (P < .0001) and previous
      meniscal surgery (P < .0001). After adjusting for patient age, knees with
      previous PM were more likely to have chondrosis than knees with previous MR (P =
      .003) or no previous meniscal surgery (P < .0001). There was no difference
      between knees without previous meniscal surgery and knees with previous MR (P =
      .7). Previous partial meniscectomy was associated with a higher rate of
      chondrosis in the same compartment compared with knees without previous meniscal
      surgery (P < .0001) and knees with previous MR (P <= .03). CONCLUSION: The status
      of articular cartilage at the time of revision ACL reconstruction relates to
      previous meniscal surgery independent of the effect of patient age. Previous
      partial meniscectomy is associated with a higher incidence of articular cartilage
      lesions, whereas previous meniscal repair is not. Although this association may
      reflect underlying differences in the knee at the time of prior surgery, it does
      suggest that meniscal repair is preferable when possible at the time of ACL
      reconstruction.

PMID- 22374945
TI  - Complete genome sequence of Mycoplasma haemocanis strain Illinois.
AB  - Mycoplasma haemocanis is a blood pathogen that may cause acute disease in
      immunosuppressed or splenectomized dogs. The genome of the strain Illinois is a
      single circular chromosome with 919,992 bp and a GC content of 35%. Analyses of
      the M. haemocanis genome will provide insights into its biology and in vitro
      cultivation requirements.

PMID- 22374946
TI  - Genome sequence of Sphingomonas sp. strain PAMC 26605, isolated from Arctic
      lichen (Ochrolechia sp.).
AB  - The endosymbiotic bacterium Sphingomonas sp. strain PAMC 26605 was isolated from
      Arctic lichens (Ochrolechia sp.) on the Svalbard Islands. Here we report the
      draft genome sequence of this strain, which could provide further insights into
      the symbiotic mechanism of lichens in extreme environments.

PMID- 22374947
TI  - Genome sequence of Weissella confusa LBAE C39-2, isolated from a wheat sourdough.
AB  - Weissella confusa is a rod-shaped heterofermentative lactic acid bacterium from
      the family of Leuconostocaceae. Here we report the draft genome sequence of the
      strain W. confusa LBAE C39-2 isolated from a traditional French wheat sourdough.

PMID- 22374948
TI  - Genome sequences of three Leuconostoc citreum strains, LBAE C10, LBAE C11, and
      LBAE E16, isolated from wheat sourdoughs.
AB  - Leuconostoc citreum is a key microorganism in fermented foods of plant origin.
      Here we report the draft genome sequence for three strains of Leuconostoc
      citreum, LBAE C10, LBAE C11, and LBAE E16, which have been isolated from
      traditional French wheat sourdoughs.

PMID- 22374949
TI  - Complete genome sequence of Rickettsia slovaca, the agent of tick-borne
      lymphadenitis.
AB  - The present study reports the complete and annotated genome sequence of the human
      pathogen Rickettsia slovaca strain 13-B, which was isolated from a Dermacentor
      tick in Slovakia in 1968. The 1.27-Mb genome provides further insights into the
      acquisition of virulence related to genome reduction in Rickettsia species.

PMID- 22374951
TI  - Complete genome sequence of clinical isolate Pantoea ananatis LMG 5342.
AB  - The enterobacterium Pantoea ananatis is an ecologically versatile species. It has
      been found in the environment, as plant epiphyte and endophyte, as an emerging
      phytopathogen, and as a presumptive, opportunistic human pathogen. Here, we
      report the complete genome sequence of P. ananatis LMG 5342, isolated from a
      human wound.

PMID- 22374950
TI  - Whole-genome sequence of the human pathogen Legionella pneumophila serogroup 12
      strain 570-CO-H.
AB  - We present the genomic sequence of the human pathogen Legionella pneumophila
      serogroup 12 strain 570-CO-H (ATCC 43290), a clinical isolate from the Colorado
      Department of Health, Denver, CO. This is the first example of a genome sequence
      of L. pneumophila from a serogroup other than serogroup 1. We highlight the
      similarities and differences relative to six genome sequences that have been
      reported for serogroup 1 strains.

PMID- 22374952
TI  - Genome sequence of the soybean symbiont Sinorhizobium fredii HH103.
AB  - Sinorhizobium fredii HH103 is a fast-growing rhizobial strain that is able to
      nodulate legumes that develop determinate nodules, e.g., soybean, and legumes
      that form nodules of the indeterminate type. Here we present the genome of HH103,
      which consists of one chromosome and five plasmids with a total size of 7.22 Mb.

PMID- 22374953
TI  - Genome sequences of four divergent multidrug-resistant Acinetobacter baumannii
      strains isolated from patients with sepsis or osteomyelitis.
AB  - Acinetobacter baumannii is a Gram-negative bacterium that causes nosocomial
      infections worldwide, with recent prevalence and higher frequency in wounded
      military personnel. Four A. baumannii strains from the Walter Reed Army Medical
      Center (WRAMC) isolated between 2008 and 2009 were sequenced, representing
      diverse, multidrug-resistant isolates from osteomyelitis or septic patients.

PMID- 22374954
TI  - Complete genome sequences of three Propionibacterium acnes isolates from the type
      IA(2) cluster.
AB  - Propionibacterium acnes is an anaerobic Gram-positive bacterium that has been
      linked to a wide range of opportunistic human infections and conditions, most
      notably acne vulgaris (I. Kurokawa et al., Exp. Dermatol. 18:821-832, 2009). We
      now present the whole-genome sequences of three P. acnes strains from the type
      IA(2) cluster which were recovered from ophthalmic infections (A. McDowell et
      al., Microbiology 157:1990-2003, 2011).

PMID- 22374955
TI  - Draft genome sequence of Pseudomonas psychrotolerans L19, isolated from copper
      alloy coins.
AB  - We report the draft genome sequence of Pseudomonas psychrotolerans strain L19,
      isolated from a European 50-cent copper alloy coin. Multiple genes potentially
      involved in copper resistance were identified; however, it is unknown if these
      copper ion resistance determinants contribute to prolonged survival of this
      strain on dry metallic copper.

PMID- 22374956
TI  - Genome sequence of Staphylococcus aureus strain 11819-97, an ST80-IV European
      community-acquired methicillin-resistant isolate.
AB  - The European methicillin-resistant Staphylococcus aureus (MRSA) clone ST80-IV has
      historically dominated community-associated infections in major parts of Europe
      and is a lineage strongly linked to skin and soft tissue infections. Here, we
      report the genome sequence of an ST80-IV representative, 11819-97, isolated from
      a skin infection in Denmark in 1997.

PMID- 22374957
TI  - Genome sequence of Streptomyces sp. strain TOR3209, a rhizosphere microecology
      regulator isolated from tomato rhizosphere.
AB  - Streptomyces sp. strain TOR3209, isolated from tomato rhizosphere, can regulate
      the rhizosphere microecology of a variety of crops. Strain TOR3209 could improve
      plant systemic resistance and promote plant growth. Here, the genome sequence of
      strain TOR3209 is reported, providing the molecular biological basis of the
      regulation mechanism of rhizosphere microecology.

PMID- 22374959
TI  - Complete genome sequence of the highly hemolytic strain Bacillus cereus F837/76.
AB  - Highly hemolytic strain Bacillus cereus F837/76 was isolated in 1976 from a
      contaminated prostate wound. The complete nucleotide sequence of this strain
      reported here counts nearly 36,500 single-nucleotide differences from the closest
      sequenced strain, Bacillus thuringiensis Al Hakam. F827/76 also contains a 10-kb
      plasmid that was not detected in the Al Hakam strain.

PMID- 22374958
TI  - Draft genome sequence of marine Streptomyces sp. strain W007, which produces
      angucyclinone antibiotics with a benz[a]anthracene skeleton.
AB  - A series of angucyclinone antibiotics have been isolated from marine Streptomyces
      sp. strain W007 and identified. Here, a draft genome sequence of Streptomyces sp.
      W007 is presented. The genome contains an intact biosynthetic gene cluster for
      angucyclinone antibiotics, which provides insight into the combinatorial
      biosynthesis of angucyclinone antibiotics produced by marine streptomycetes.

PMID- 22374960
TI  - Draft genome sequence of Clostridium sporogenes PA 3679, the common nontoxigenic
      surrogate for proteolytic Clostridium botulinum.
AB  - Clostridium sporogenes PA 3679 is widely used as a nontoxigenic surrogate for
      proteolytic strains of Clostridium botulinum in the derivation and validation of
      thermal processes in food. Here we report the draft assembly and annotation of
      the C. sporogenes PA 3679 genome. Preliminary analysis demonstrates a high degree
      of relatedness between C. sporogenes PA 3679 and sequenced strains of proteolytic
      C. botulinum.

PMID- 22374961
TI  - Genome sequence of Comamonas testosteroni ATCC 11996, a representative strain
      involved in steroid degradation.
AB  - Comamonas testosteroni strains belong to the family of Comamonadaceae and are
      known for their ability to utilize steroid compounds as carbon source. Here, we
      present the draft genome sequence of strain ATCC 11996, with a G+C content of
      61.48%.

PMID- 22374962
TI  - Genome sequence of the facultative anaerobic arsenite-oxidizing and nitrate
      reducing bacterium Acidovorax sp. strain NO1.
AB  - Acidovorax sp. strain NO1, isolated from gold mine soil, was shown to be a
      facultative anaerobic arsenite-oxidizing and nitrate-reducing bacterium. The
      reported draft genome predicts the presence of genes involved in arsenic
      metabolism, nitrate reduction, phosphate transport, and multiple metal
      resistances and indicates putative horizontal gene transfer events.

PMID- 22374963
TI  - Genome sequence of the cycloprodigiosin-producing bacterial strain
      Pseudoalteromonas rubra ATCC 29570(T).
AB  - The cycloprodigiosin biosynthetic gene cluster has not been reported. We
      sequenced the genome of a cycloprodigiosin-producing bacterial strain,
      Pseudoalteromonas rubra ATCC 29570(T). Analysis revealed a probable
      cycloprodigiosin biosynthetic cluster, providing a good model for the study of
      cycloprodigiosin synthesis and regulation.

PMID- 22374964
TI  - Draft genome sequence of Vibrio fischeri SR5, a strain isolated from the light
      organ of the Mediterranean squid Sepiola robusta.
AB  - Here, we describe the draft genome sequence of Vibrio fischeri SR5, a squid
      symbiotic isolate from Sepiola robusta in the Mediterranean Sea. This 4.3-Mbp
      genome sequence represents the first V. fischeri genome from an S. robusta
      symbiont and the first from outside the Pacific Ocean.

PMID- 22374965
TI  - Evidence that contamination by lipopolysaccharide confounds in vitro studies of
      adiponectin activity in bone.
AB  - Adiponectin, a hormone produced and secreted from adipose tissue, circulates at
      levels that are inversely related to visceral fat mass and bone mineral density.
      Adiponectin receptors are expressed in bone cells, and several studies have shown
      that adiponectin affects bone phenotype and might play a role in the cross talk
      between fat and bone tissues. In the current study, we determined global changes
      in gene expression induced by adiponectin in mouse bone marrow cells, in order to
      identify the molecular mechanisms that mediate adiponectin's effect to inhibit
      osteoclast differentiation in these cultures. The gene signature that was
      produced by microarray analysis was very similar to a signature produced by
      activation of type I interferons (IFN), and we therefore tested the hypothesis
      that the adiponectin preparation, although marketed as "lipopolysaccharide (LPS)
      free", was contaminated with LPS that induced an IFN response in the bone marrow
      cells. Heat inactivation of the adiponectin preparation and the use of small
      interfering RNA to knockdown the AdipoR1 receptor had not diminished the activity
      of the adiponectin preparation to induce the IFN target genes Ccl5 and Irf7.
      Thus, the changes in gene expression determined in the bone marrow cultures are
      likely to be the result of a combination of adiponectin and LPS effects. Our
      study suggests that the purity of commercially available proteins needs to be
      verified and that experimental results of adiponectin activity in vitro should be
      interpreted cautiously.

PMID- 22374966
TI  - Transcriptome analysis reveals differentially expressed transcripts in rat
      adrenal zona glomerulosa and zona fasciculata.
AB  - In mammals, aldosterone is produced in the zona glomerulosa (zG), the outermost
      layer of the adrenal cortex, whereas glucocorticoids are produced in adjacent
      zona fasciculata (zF). However, the cellular mechanisms controlling the zonal
      development and the differential hormone production (i.e. functional zonation)
      are poorly understood. To explore the mechanisms, we defined zone-specific
      transcripts in this study. Eleven-week-old male rats were used and adrenal
      tissues were collected from zG and zF using laser-capture microdissection. RNA
      was isolated, biotin labeled, amplified, and hybridized to Illumina microarray
      chips. The microarray data were compared by fold change calculations. In zG, 235
      transcripts showed more than a 2-fold up-regulation compared to zF with
      statistical significance. Similarly, 231 transcripts showed up-regulation in zF.
      The microarray findings were validated using quantitative RT-PCR and
      immunohistochemical staining on selected transcripts, including Cyp11b2 (zG/zF:
      214.2x), Rgs4 (68.4x), Smoc2 (49.3x), and Mia1 (43.1x) in zG as well as Ddah1
      (zF/zG 16.2x), Cidea (15.5x), Frzb (9.5x), and Hsd11b2 (8.3x) in zF. The lists of
      transcripts obtained in the current study will be an invaluable tool for the
      elucidation of cellular mechanisms leading to zG and zF functional zonation.

PMID- 22374967
TI  - Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ
      induced diabetic rats are improved by long-term melatonin treatment.
AB  - Diabetes mellitus is a product of low insulin sensibility and pancreatic beta
      cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal
      period by the fifth day of age develop the classic diabetic picture of
      hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin
      resistance in adulthood. In this study, we investigated whether the effect of
      long-term treatment with melatonin can improve insulin resistance and other
      metabolic disorders in these animals. At the fourth week of age, diabetic animals
      started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking
      water at night. Animals were then killing, and the sc, epididymal (EP), and
      retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte
      isolation for morphometric analysis as well as for measuring glucose uptake,
      oxidation, and incorporation of glucose into lipids. Blood samples were collected
      for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia,
      and polyphagia as well as improved insulin resistance as demonstrated by constant
      glucose disappearance rate and homeostasis model of assessment-insulin
      resistance. However, melatonin treatment was unable to recover body weight
      deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and
      fructosamine levels were completely recovered by melatonin, whereas neither
      plasma insulin level nor insulin secretion capacity was improved in diabetic
      animals. Furthermore, melatonin caused a marked delay in the sexual development,
      leaving genital structures smaller than those of nontreated diabetic animals.
      Melatonin treatment improved the responsiveness of adipocytes to insulin in
      diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose
      oxidation, and incorporation of glucose into lipids (EP and RP), an effect that
      seems partially related to an increased expression of insulin receptor substrate
      1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion,
      melatonin treatment was capable of ameliorating the metabolic abnormalities in
      this particular diabetes model, including insulin resistance and promoting a
      better long-term glycemic control.

PMID- 22374968
TI  - Systemic leptin administration in supraphysiological doses maintains bone mineral
      density and mechanical strength despite significant weight loss.
AB  - The effects of leptin on bone are controversial. Although in vitro studies have
      shown that leptin stimulates osteoblast differentiation and mineralization and
      inhibits osteoclastogenesis, some rodent studies have shown that leptin
      administered centrally might result in decreased bone formation. In the present
      study we have investigated the skeletal effects of supraphysiological
      concentrations of leptin administered sc to rats. Female Fischer rats were given
      leptin 100 MUg/d, 200 MUg/d, or saline by continuous infusion for 9 wk. Bone
      mineral density (BMD) was measured by dual energy x-ray absorptiometry, bone
      microarchitecture was analyzed by micro-computed tomography, and biomechanical
      properties were tested by three-point bending experiments. At the end of the
      study, the body weight was significantly lower in rats receiving leptin compared
      with controls (-10.8% and -12.0% in low- and high-dose leptin groups,
      respectively). The high-dose leptin group also significantly lost weight compared
      with baseline. The plasma leptin concentration was 14- and 33-fold increased in
      the low- and high-dose groups, respectively. No significant differences in
      femoral BMD were observed. Whole-body BMD was significantly lower in the low-dose
      leptin group, whereas there was no difference between the high-dose leptin group
      and the control. Mechanical strength and microarchitecture were similar in the
      high-dose and the control group. The low-dose group, however, had decreased
      cortical volume in the femoral metaphysis, lowered bone strength, and altered
      moment of inertia. In conclusion, leptin given at very high doses maintains BMD,
      microarchitecture, and mechanical strength in female rats, despite a significant
      decrease in body weight.

PMID- 22374970
TI  - Lipid-induced endoplasmic reticulum stress in liver cells results in two distinct
      outcomes: adaptation with enhanced insulin signaling or insulin resistance.
AB  - Chronically elevated fatty acids contribute to insulin resistance through poorly
      defined mechanisms. Endoplasmic reticulum (ER) stress and the subsequent unfolded
      protein response (UPR) have been implicated in lipid-induced insulin resistance.
      However, the UPR is also a fundamental mechanism required for cell adaptation and
      survival. We aimed to distinguish the adaptive and deleterious effects of lipid
      induced ER stress on hepatic insulin action. Exposure of human hepatoma HepG2
      cells or mouse primary hepatocytes to the saturated fatty acid palmitate enhanced
      ER stress in a dose-dependent manner. Strikingly, exposure of HepG2 cells to
      prolonged mild ER stress activation induced by low levels of thapsigargin,
      tunicamycin, or palmitate augmented insulin-stimulated Akt phosphorylation. This
      chronic mild ER stress subsequently attenuated the acute stress response to high
      level palmitate challenge. In contrast, exposure of HepG2 cells or hepatocytes to
      severe ER stress induced by high levels of palmitate was associated with reduced
      insulin-stimulated Akt phosphorylation and glycogen synthesis, as well as
      increased expression of glucose-6-phosphatase. Attenuation of ER stress using
      chemical chaperones (trimethylamine N-oxide or tauroursodeoxycholic acid)
      partially protected against the lipid-induced changes in insulin signaling. These
      findings in liver cells suggest that mild ER stress associated with chronic low
      level palmitate exposure induces an adaptive UPR that enhances insulin signaling
      and protects against the effects of high-level palmitate. However, in the absence
      of chronic adaptation, severe ER stress induced by high-level palmitate exposure
      induces deleterious UPR signaling that contributes to insulin resistance and
      metabolic dysregulation.

PMID- 22374969
TI  - Multiligand specificity and wide tissue expression of GPRC6A reveals new
      endocrine networks.
AB  - Emerging evidence supports the hypothesis that the skeleton is an endocrine organ
      that regulates energy metabolism through the release of the osteoblast-derived
      hormone, osteocalcin (Ocn). This bone-pancreas endocrine network is controversial
      because important gaps remain to be filled in our knowledge of the physiological
      effects of Ocn in multiple organs and the complex alterations in other hormonal
      networks induced by Ocn administration. A key step toward understanding the
      integrative regulation of energy metabolism by bone is the identification of GPCR
      family C group 6 member A (GPRC6A) as the Ocn receptor. GPRC6A is an amino acid
      sensing G protein-coupled receptor highly expressed in beta-cells and is
      activated by recombinant Ocn in vitro and in vivo but that is widely expressed in
      tissues other than the pancreas and is capable of sensing multiple structurally
      unrelated ligands, including l-amino acids, cations, and anabolic steroids in
      addition to Ocn. The broad expression and multiligand specificity of GPRC6A is
      identifying both systemic and paracrine regulation of seemingly disparate
      biological processes, ranging from energy metabolism, sexual reproduction,
      hypothalamic-pituitary function, bone formation, and prostate cancer. Consistent
      with the existence of more complex endocrine networks, ablation of GPRC6A in
      Gprc6a(-/-) mice results in complex metabolic abnormalities, including obesity,
      glucose intolerance, hepatic steatosis, insulin resistance, hyperphosphatemia,
      osteopenia, plus several hormonal abnormalities, including decreased circulating
      testosterone, IGF-I, and insulin and increased estradiol, LH, GH, and leptin.
      Recombinant Ocn also regulates testosterone production by the testes and male
      fertility through a GPRC6A-dependent mechanism, and testosterone regulation of LH
      secretion is abnormal in Gprc6a(-/-) mice. Thus, GPRC6A, as the biologically
      relevant receptor for Ocn, defines not only a molecular mechanism for linking
      bone metabolism with metabolic regulation of beta-cells and sexual reproduction
      but also as a receptor shared by testosterone and dietary factors, and it is also
      involved in multiple endocrine networks integrating the functions of pancreas,
      muscle, liver, fat, testes, bone, and the hypothalamic-pituitary axis with
      alterations in both environmental and endogenous ligands.

PMID- 22374972
TI  - Fasting energy homeostasis in mice with adipose deficiency of desnutrin/adipose
      triglyceride lipase.
AB  - Adipose triglyceride lipase (ATGL) catalyzes the first step of lipolysis of
      cytoplasmic triacylglycerols in white adipose tissue (WAT) and several other
      organs. We created adipose-specific ATGL-deficient (ATGLAKO) mice. In these mice,
      in vivo lipolysis, measured as the increase of plasma nonesterified fatty acid
      and glycerol levels after injection of a beta3-adrenergic agonist, was
      undetectable. In isolated ATGLAKO adipocytes, beta3-adrenergic-stimulated
      glycerol release was 10-fold less than in controls. Under fed conditions, ATGLAKO
      mice had normal viability, mild obesity, low plasma nonesterified fatty acid
      levels, increased insulin sensitivity, and increased daytime food intake. After 5
      h of fasting, ATGLAKO WAT showed phosphorylation of the major protein kinase A
      mediated targets hormone-sensitive lipase and perilipin A and ATGLAKO liver
      showed low glycogen and triacylglycerol contents. During a 48-h fast, ATGLAKO
      mice developed striking and complex differences from controls: progressive
      reduction of oxygen consumption, high respiratory exchange ratio, consistent with
      reduced fatty acid availability for energy production, lethargy, hypothermia, and
      undiminished fat mass, but greater loss of lean mass than controls. Plasma of 48
      h-fasted ATGLAKO mice had a unique pattern: low 3-hydroxybutyrate, insulin,
      adiponectin, and fibroblast growth factor 21 with elevated leptin and
      corticosterone. ATGLAKO WAT, liver, skeletal muscle, and heart showed increased
      levels of mRNA related to autophagy and proteolysis. In murine ATGL deficiency,
      adipose lipolysis is critical for fasting energy homeostasis, and fasting imposes
      proteolytic stress on many organs, including heart and skeletal muscle.

PMID- 22374971
TI  - Assessment of epigenetic contributions to sexually-dimorphic Kiss1 expression in
      the anteroventral periventricular nucleus of mice.
AB  - The Kiss1 gene, which encodes kisspeptin and is critical for reproduction, is
      sexually differentiated in the hypothalamic anteroventral periventricular
      (AVPV)/rostral periventricular (PeN) nuclei. Specifically, female rodents have
      higher AVPV/PeN Kiss1 expression than males, but how this Kiss1 sex difference is
      induced in early development is poorly understood. Here, we explored the
      contribution of epigenetic mechanisms to the establishment of the AVPV/PeN Kiss1
      sex difference, focusing on histone deacetylation and DNA methylation. First, we
      utilized postnatal pharmacological blockade of histone deacetylation and analyzed
      Kiss1 expression in the AVPV/PeN. Postnatal disruption of histone deacetylase
      modestly increased AVPV Kiss1 cell number in both sexes but did not alter the
      Kiss1 sex difference. Next, we assessed whether the level of CpG methylation,
      which can influence transcription factor binding and gene expression, in the
      murine Kiss1 gene differs between males and females. We found significant sex
      differences in methylation at several CpG sites in the putative promoter and
      first intron of the Kiss1 gene in the AVPV/PeN, but not in the arcuate (which
      lacks adult Kiss1 sex differences), suggesting that differential methylation of
      the Kiss1 gene may influence sexually-dimorphic Kiss1 expression in the AVPV/PeN.
      Transgenic impairment of methyl CpG-binding protein-2 function did not eliminate
      the Kiss1 sex difference, indicating that other methylation factors are involved.
      Interestingly, CpG methylation in the AVPV/PeN was lower in males than females,
      suggesting that transcriptional repressors may contribute to the AVPV/PeN Kiss1
      sex difference, a possibility supported by in silico identification of putative
      repressor binding sites near some of the sexually-dimorphic CpG.

PMID- 22374973
TI  - Gonadotropin-inhibitory hormone inhibits GnRH-induced gonadotropin subunit gene
      transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LbetaT2 cells.
AB  - A neuropeptide that directly inhibits gonadotropin secretion from the pituitary
      was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The
      presence and functional roles of GnIH orthologs, RF-amide-related peptides
      (RFRP), that possess a common C-terminal LPXRF-amide (X = L or Q) motif have also
      been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and
      release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus
      via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is
      an important hypothalamic neuropeptide controlling reproduction, but the detailed
      signaling pathway mediating the inhibitory effect of GnIH on target cells is
      still unknown. In the present study, we investigated the pathway of GnIH cell
      signaling and its possible interaction with GnRH signaling using a mouse
      gonadotrope cell line, LbetaT2. First, we demonstrated the expression of GnIH
      receptor mRNA in LbetaT2 cells by RT-PCR. We then examined the inhibitory effects
      of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling
      events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by
      using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that
      mRFRP function as an inhibitor of adenylate cyclase. We further showed that mRFRP
      inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by
      the inhibition of the protein kinase A pathway. Finally, we demonstrated that
      mRFRP inhibited GnRH-stimulated gonadotropin subunit gene transcriptions and also
      LH release. Taken together, the results indicate that mRFRP function as GnIH to
      inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting
      adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LbetaT2
      cells.

PMID- 22374974
TI  - Prolonged exposure to insulin induces mitochondrion-derived oxidative stress
      through increasing mitochondrial cholesterol content in hepatocytes.
AB  - We addressed the link between excessive exposure to insulin and mitochondrion
      derived oxidative stress in this study and found that prolonged exposure to
      insulin increased mitochondrial cholesterol in cultured hepatocytes and in mice
      and stimulated production of reactive oxygen species (ROS) and decreased the
      reduced glutathione to glutathione disulfide ratio in cultured hepatocytes.
      Exposure of isolated hepatic mitochondria to cholesterol alone promoted ROS
      emission. The oxidative stress induced by the prolonged exposure to insulin was
      prevented by inhibition of cholesterol synthesis with simvastatin. We further
      found that prolonged exposure to insulin decreased mitochondrial membrane
      potential and the increased ROS production came from mitochondrial respiration
      complex I. Finally, we observed that prolonged exposure to insulin decreased
      mitochondrial membrane fluidity in a cholesterol synthesis-dependent manner.
      Together our results demonstrate that excess exposure to insulin causes
      mitochondrion-derived oxidative stress through cholesterol synthesis in
      hepatocytes.

PMID- 22374976
TI  - Role of fibroblast growth factor 21 (FGF21) in undernutrition-related attenuation
      of growth in mice.
AB  - Reduced caloric intake in mammals causes reduced skeletal growth and GH
      insensitivity. However, the underlying molecular mechanisms are not fully
      elucidated. The aim of this study was to determine whether the increased activity
      of fibroblast growth factor 21 (FGF21) during chronic undernutrition in mice
      causes GH insensitivity and growth failure. After 4 wk of food restriction, fgf21
      knockout (KO) mice exhibited greater body and tibial growth than their wild-type
      (WT) littermates. Daily injections of recombinant human FGF21 in a subgroup of
      food-restricted fgf21 KO mice prevented these differences in body and tibial
      growth. At the end of the 4-wk food restriction, GH binding and GH receptor
      expression were reduced in the liver and in the growth plate of food-restricted
      WT mice (compared to WT mice fed ad libitum), whereas they were similar between
      food-restricted and ad libitum KO mice. In addition, a single injection of GH
      induced greater liver signal transducer and activator of transcription 5
      phosphorylation and IGF-I mRNA in food-restricted KO mice than in WT mice.
      Lastly, in the tibial growth plate of food-restricted WT mice, FGF21 mRNA and
      protein expression was greater than that of WT mice fed ad libitum. In contrast,
      the IGF-I mRNA and protein expression was smaller. Our findings support a
      causative role for FGF21 in the inhibition of skeletal growth during prolonged
      undernutrition. Such role may be mediated by the antagonistic effect of FGF21 on
      GH action in the liver and, possibly, in the growth plate.

PMID- 22374977
TI  - Perinatal maternal dietary supplementation of omega3-fatty acids transiently
      affects bone marrow microenvironment, osteoblast and osteoclast formation, and
      bone mass in male offspring.
AB  - It is increasingly evident that micronutrient environment experienced before
      birth and in infancy is important for achieving optimal bone mass by adolescence
      and maintaining bone health. This study determined whether maternal
      supplementation with omega3-polyunsaturated fatty acids (n3FA) improved offspring
      bone growth and adult bone mass. Female rats were fed a diet containing 0.1%
      (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy
      and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth
      plate and metaphysis structure, osteoblast/osteoclast density and
      differentiation, and gene expression were assessed in offspring at 3 wk
      (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation
      elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate
      heights were unaffected at any age, the resting zone thickness was increased in
      both male and female offspring at 3 wk. In n3FA males, but not females, bone
      trabecular number and thickness were increased at 3 wk but not other ages. The wk
      3 n3FA males also exhibited an increased bone volume, an increased osteoblast but
      decreased osteoclast density, and lower expression of osteoclastogenic cytokines
      receptor activator of nuclear factor-kappaB ligand, TNF-alpha, and IL-6. No
      effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA
      supplementation is associated with increased bone formation, decreased
      resorption, and a higher bone mass in males, but not in females, at weaning;
      these effects do not persist into adolescence and adulthood and are unlikely to
      produce lasting improvements in bone health.

PMID- 22374975
TI  - Hematopoetic prostaglandin D synthase: an ESR1-dependent oviductal epithelial
      cell synthase.
AB  - Oviductal disease is a primary cause of infertility, a problem that largely stems
      from excessive inflammation of this key reproductive organ. Our poor
      understanding of the mechanisms regulating oviductal inflammation restricts our
      ability to diagnose, treat, and/or prevent oviductal disease. Using mice, our
      objective was to determine the spatial localization, regulatory mechanism, and
      functional attributes of a hypothesized regulator of oviductal inflammation, the
      hematopoietic form of prostaglandin D synthase (HPGDS). Immunohistochemistry
      revealed specific localization of HPGDS to the oviduct's epithelium. In the
      isthmus, expression of HPGDS was consistent. In the ampulla, expression of HPGDS
      appeared dependent upon stage of the estrous cycle. HPGDS was expressed in the
      epithelium of immature and cycling mice but not in the oviducts of estrogen
      receptor alpha knockouts. Two receptor subtypes bind PGD2: PGD2 receptor and G
      protein-coupled receptor 44. Expression of mRNA for Ptgdr was higher in the
      epithelial cells (EPI) than in the stroma (P < 0.05), whereas mRNA for Gpr44 was
      higher in the stroma than epithelium (P < 0.05). Treatment of human oviductal EPI
      with HQL-79, an inhibitor of HPGDS, decreased cell viability (P < 0.05).
      Treatment of mice with HQL-79 increased mRNA for chemokine (C-C motif) ligands 3,
      4, and 19; chemokine (C-X-C motif) ligands 11 and 12; IL-13 and IL-17B; and TNF
      receptor superfamily, member 1b (P < 0.02 for each mRNA). Overall, these results
      suggest that HPGDS may play a role in the regulation of inflammation and EPI
      health within the oviduct.

PMID- 22374978
TI  - Protein kinase C: a putative new target for the control of human medullary
      thyroid carcinoma cell proliferation in vitro.
AB  - We investigate the role of protein kinase C (PKC) in the control of medullary
      thyroid carcinoma (MTC) cell proliferation by a PKC inhibitor, Enzastaurin, in
      human MTC primary cultures and in the TT cell line. We found that PKC inhibition
      reduces cell proliferation by inducing caspase-mediated apoptosis and blocks the
      stimulatory effect of IGF-I on calcitonin secretion. Enzastaurin reduces
      PKCbetaII (Thr500) phosphorylation, indicating a direct involvement of this
      isoform as well as the phosphorylated levels of Akt (Ser 473) and glycogen
      synthase kinase (Ser9), PKC pathway downstream targets and pharmacodynamic
      markers for PKC inhibition. PKCbetaII and PKCdelta enzyme isoforms expression and
      localization were investigated. These data indicate that in vitro PKC is involved
      in the control of human MTC proliferation and survival by modulating apoptosis,
      with a mechanism that implicates PKCbetaII inhibition and translocation in
      different subcellular compartments. Targeting PKC may represent a useful
      therapeutic approach for controlling MTC proliferation.

PMID- 22374979
TI  - Bone marrow stromal cells create a permissive microenvironment for myeloma
      development: a new stromal role for Wnt inhibitor Dkk1.
AB  - The rapid progression of multiple myeloma is dependent upon cellular interactions
      within the bone marrow microenvironment. In vitro studies suggest that bone
      marrow stromal cells (BMSC) can promote myeloma growth and survival and
      osteolytic bone disease. However, it is not possible to recreate all cellular
      aspects of the bone marrow microenvironment in an in vitro system, and the
      contributions of BMSCs to myeloma pathogenesis in an intact, immune competent, in
      vivo system are unknown. To investigate this, we used a murine myeloma model that
      replicates many features of the human disease. Coinoculation of myeloma cells and
      a BMSC line, isolated from myeloma-permissive mice, into otherwise nonpermissive
      mice resulted in myeloma development, associated with tumor growth within bone
      marrow and osteolytic bone disease. In contrast, inoculation of myeloma cells
      alone did not result in myeloma. BMSCs inoculated alone induced osteoblast
      suppression, associated with an increase in serum concentrations of the Wnt
      signaling inhibitor, Dkk1. Dkk1 was highly expressed in BMSCs and in myeloma
      permissive bone marrow. Knockdown of Dkk1 expression in BMSCs decreased their
      ability to promote myeloma and the associated bone disease in mice. Collectively,
      our results show novel roles of BMSCs and BMSC-derived Dkk1 in the pathogenesis
      of multiple myeloma in vivo.

PMID- 22374980
TI  - Increased CD8+ T-cell function following castration and immunization is countered
      by parallel expansion of regulatory T cells.
AB  - Although androgen ablation therapy is effective in treating primary prostate
      cancers, a significant number of patients develop incurable castration-resistant
      disease. Recent studies have suggested a potential synergy between vaccination
      and androgen ablation, yet the enhanced T-cell function is transient. Using a
      defined tumor antigen model, UV-8101-RE, we found that concomitant castration
      significantly increased the frequency and function of antigen-specific CD8(+) T
      cells early after the immunization of wild-type mice. However, at a late time
      point after immunization, effector function was reduced to the same level as
      noncastrated mice and was accompanied by a concomitant amplification in
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) following immunization. We
      investigated whether Treg expansion occurred following castration of prostate
      tumor-bearing mice. In the prostate-specific Pten(-/-) mouse model of prostate
      cancer, we observed an accelerated Treg expansion in mice bearing the castration
      resistant endogenous prostate tumor, which prevented effector responses to UV
      8101-RE. Treg depletion together with castration elicited a strong CD8(+) T-cell
      response to UV-8101-RE in Pten(-/-) mice and rescued effector function in
      castrated and immunized wild-type mice. In addition, Treg expansion in Pten(-/-)
      mice was prevented by in vivo interleukin (IL)-2 blockade suggesting that
      increased IL-2 generated by castration and immunization promotes Treg expansion.
      Our findings therefore suggest that although effector responses are augmented by
      castration, the concomitant expansion of Tregs is one mechanism responsible for
      only transient immune potentiation after androgen ablation.

PMID- 22374981
TI  - Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast
      cancer risk.
AB  - Few studies have evaluated the association between DNA methylation in white blood
      cells (WBC) and the risk of breast cancer. The evaluation of WBC DNA methylation
      as a biomarker of cancer risk is of particular importance as peripheral blood is
      often available in prospective cohorts and easier to obtain than tumor or normal
      tissues. Here, we used prediagnostic blood samples from three studies to analyze
      WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome
      wide DNA methylation in long interspersed nuclear element-1 (LINE1) repetitive
      elements. Samples were from a case-control study derived from a cohort of high
      risk breast cancer families (KConFab) and nested case-control studies in two
      prospective cohorts: Breakthrough Generations Study (BGS) and European
      Prospective Investigation into Cancer and Nutrition (EPIC). Bisulfite
      pyrosequencing was used to quantify methylation from 640 incident cases of
      invasive breast cancer and 741 controls. Quintile analyses for ATMmvp2a showed an
      increased risk of breast cancer limited to women in the highest quintile [OR,
      1.89; 95% confidence interval (CI), 1.36-2.64; P = 1.64 * 10(-4)]. We found no
      significant differences in estimates across studies or in analyses stratified by
      family history or menopausal status. However, a more consistent association was
      observed in younger than in older women and individually significant in KConFab
      and BGS, but not EPIC. We observed no differences in LINE1 or ATMmvp2b
      methylation between cases and controls. Together, our findings indicate that WBC
      DNA methylation levels at ATM could be a marker of breast cancer risk and further
      support the pursuit of epigenome-wide association studies of peripheral blood DNA
      methylation.

PMID- 22374982
TI  - Tumor vascular microenvironment determines responsiveness to photodynamic
      therapy.
AB  - The efficacy of photodynamic therapy (PDT) depends upon the delivery of both
      photosensitizing drug and oxygen. In this study, we hypothesized that local
      vascular microenvironment is a determinant of tumor response to PDT. Tumor
      vascularization and its basement membrane (collagen) were studied as a function
      of supplementation with basement membrane matrix (Matrigel) at the time of tumor
      cell inoculation. Effects on vascular composition with consequences to tumor
      hypoxia, photosensitizer uptake, and PDT response were measured. Matrigel
      supplemented tumors developed more normalized vasculature, composed of smaller
      and more uniformly spaced blood vessels than their unsupplemented counterparts,
      but these changes did not affect tumor oxygenation or PDT-mediated direct
      cytotoxicity. However, PDT-induced vascular damage increased in Matrigel
      supplemented tumors, following an affinity of the photosensitizer Photofrin for
      collagen-containing vascular basement membrane coupled with increased collagen
      content in these tumors. The more highly collagenated tumors showed more vascular
      congestion and ischemia after PDT, along with a higher probability of curative
      outcome that was collagen dependent. In the presence of photosensitizer-collagen
      localization, PDT effects on collagen were evidenced by a decrease in its
      association with vessels. Together, our findings show that photosensitizer
      localization to collagen increases vascular damage and improves treatment
      efficacy in tumors with greater collagen content. The vascular basement membrane
      is thus identified to be a determinant of therapeutic outcome in PDT of tumors.

PMID- 22374984
TI  - Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by
      exacerbating immune escape and vessel abnormalization.
AB  - Histidine-rich glycoprotein (HRG) is a 75-kDa heparin-binding plasma protein
      implicated in the regulation of tumor growth and vascularization. In this study,
      we show that hrg(-/-) mice challenged with fibrosarcoma or pancreatic carcinoma
      grow larger tumors with increased metastatic properties. Compared with wild-type
      mice, fibrosarcomas in hrg(-/-) mice were more hypoxic, necrotic, and less
      perfused, indicating enhanced vessel abnormalization. HRG deficiency was
      associated with a suppressed antitumor immune response, with both increased
      infiltration of M2 marker-expressing macrophages and decreased infiltration of
      dendritic cells and cytotoxic T cells. Analysis of transcript expression in tumor
      associated as well as peritoneal macrophages from hrg(-/-) mice revealed an
      increased expression of genes associated with a proangiogenic and
      immunoinhibitory phenotype. In accordance, expression arrays conducted on HRG
      treated peritoneal macrophages showed induction of genes involved in
      extracellular matrix biology and immune responsiveness. In conclusion, our
      findings show that macrophages are a direct target of HRG. HRG loss influences
      macrophage gene regulation, leading to excessive stimulation of tumor
      angiogenesis, suppression of tumor immune response, and increased tumor growth
      and metastatic spread.

PMID- 22374983
TI  - Densely granulated murine NK cells eradicate large solid tumors.
AB  - Natural killer (NK) cells inhibit early stages of tumor formation, recurrence,
      and metastasis. Here, we show that NK cells can also eradicate large solid
      tumors. Eradication depended on the massive infiltration of proliferating NK
      cells due to interleukin 15 (IL-15) released and presented by the cancer cells in
      the tumor microenvironment. Infiltrating NK cells had the striking morphologic
      feature of being densely loaded with periodic acid-Schiff-positive, diastase
      resistant granules, resembling uterine NK cells. Perforin-mediated killing by
      these densely granulated NK cells was essential for tumor eradication. Expression
      of the IL-15 receptor alpha on cancer cells was needed to efficiently induce
      granulated NK cells, and expression on host stromal cells was essential to
      prevent tumor relapse after near complete destruction. These results indicate
      that IL-15 released at the cancer site induces highly activated NK cells that
      lead to eradication of large solid tumors.

PMID- 22374985
TI  - Comparison of effects of 3 and 7% hypertonic saline nebulization on lung function
      in children with cystic fibrosis: a double-blind randomized, controlled trial.
AB  - BACKGROUND: Beneficial effects of hypertonic saline on lung function in cystic
      fibrosis patients are well documented. However, the effects of various
      concentrations of hypertonic saline are not well studied. We, therefore, compared
      the effects of 3 and 7% hypertonic saline administered by nebulization on lung
      function in children with cystic fibrosis. METHOD: In a double-blind randomized
      controlled trial, 31 children with cystic fibrosis were randomized to receive
      either 3% saline or 7% saline nebulization twice daily for 28 days. Spirometry
      was performed and functional status was measured on Day 14 and 28. RESULTS: Of 31
      children enrolled in the study, 30 completed the 28 days follow up (15 in each
      group). Percentage change in Forced Expiratory Volume during first second
      (FEV(1)) from baseline to Day 14 and on Day 28 was significantly higher in the
      group receiving 3% saline as compared with those receiving 7% saline inhalation.
      There was some decrease in FEV(1) (percentage predicted) immediately after 7%
      saline inhalation unlike 3% saline. The functional status remained comparable
      between the two groups. CONCLUSION: The results suggest that 3% hypertonic saline
      nebulization was better than 7% saline inhalation. There is a need for studies
      with larger sample size and longer duration to confirm our results.

PMID- 22374986
TI  - Engineering the first chimeric antibody in targeting intracellular PRL-3
      oncoprotein for cancer therapy in mice.
AB  - Antibodies are considered as 'magic bullets' because of their high specificity.
      It is believed that antibodies are too large to routinely enter the cytosol, thus
      antibody therapeutic approach has been limited to extracellular or secreted
      proteins expressed by cancer cells. However, many oncogenic proteins are
      localized within the cell. To explore the possibility of antibody therapies
      against intracellular targets, we generated a chimeric antibody targeting the
      intracellular PRL-3 oncoprotein to assess its antitumor activities in mice.
      Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and
      specifically reduce the formation of PRL-3 expressing metastatic tumors. We
      further found that natural killer (NK) cells were important in mediating the
      therapeutic effect, which was only observed in a nude mouse model (T-cell
      deficient), but not in a Severe Combined Immunodeficiency' (scid ) mouse model (B
      and T-cell deficient), indicating the anticancer effect also depends on host B
      cell activity. Our study involving 377 nude and scid mice suggest that antibodies
      targeting intracellular proteins can be developed to treat cancer.

PMID- 22374987
TI  - Changes in body composition and mitochondrial DNA in HIV-1-infected patients
      switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a
      substudy of the BICOMBO trial.
AB  - BACKGROUND: Fat distribution, bone mineral density (BMD) and mitochondrial DNA
      (mtDNA) may improve, in the long-term, after switching from nucleoside reverse
      transcriptase inhibitors (NRTIs) to fixed-dose abacavir (ABC)/lamivudine (3TC) or
      tenofovir (TDF)/emtricitabine (FTC). METHODS: This was a prospective, randomized,
      open-label, multicentre substudy of the BICOMBO trial in which virologically
      suppressed patients had their NRTIs switched to ABC/3TC or TDF/FTC. Whole-body
      dual-energy X-ray absorptiometry (DXA) was used to measure limb, trunk and total
      body fat and total BMD. Lumbar and hip DXA scans were used to measure lumbar and
      hip BMD. Fat mass ratio (FMR; % trunk fat/% leg fat by whole-body DXA) was used
      to assess fat distribution. mtDNA was measured in peripheral blood mononuclear
      cells (PBMCs). Parameters of interest were measured at baseline, 48 and 96 weeks,
      and were compared between treatment groups. RESULTS: Of 56 patients included, 45
      (20 ABC/3TC and 25 TDF/FTC) completed the substudy. After 96 weeks, ABC/3TC (+756
      g, +12.1%) and TDF/FTC (+337 g, +7.6%) led to non-significantly different
      increases in limb fat (P=0.60). By contrast, trunk fat showed a significant
      increase (P=0.04) with ABC/3TC (+1,184 g, +10.6%) relative to TDF/FTC (-370 g, 
      4.2%). Median (IQR) FMR remained unchanged with ABC/3TC (-0.01 [-0.16-0.06];
      P=0.23), but it decreased significantly with TDF/FTC (-0.13 [-0.30-0.00];
      P=0.007). Total BMD and mtDNA significantly increased after 96 weeks, without
      differences between groups. CONCLUSIONS: Switching from NRTIs to either ABC/3TC
      or TDF/FTC led to similar increases in limb fat, BMD and PBMC mtDNA after 96
      weeks.

PMID- 22374988
TI  - Inhibition of influenza A virus replication by antagonism of a PI3K-AKT-mTOR
      pathway member identified by gene-trap insertional mutagenesis.
AB  - BACKGROUND: Host genes serving potential roles in virus replication may be
      exploited as novel antiviral targets. METHODS: Small interfering RNA (siRNA)
      mediated knockdown of host gene expression was used to validate candidate genes
      in screens against six unrelated viruses, most importantly influenza. A mouse
      model of influenza A virus infection was used to evaluate the efficacy of a
      candidate FDA-approved drug identified in the screening effort. RESULTS: Several
      genes in the PI3K-AKT-mTOR pathway were found to support broad-spectrum viral
      replication in vitro by RNA interference. This led to the discovery that
      everolimus, an mTOR inhibitor, showed in vitro antiviral activity against cowpox,
      dengue type 2, influenza A, rhino- and respiratory syncytial viruses. In a lethal
      mouse infection model of influenza A (H1N1 and H5N1) virus infection, everolimus
      treatment (1 mg/kg/day) significantly delayed death but could not prevent
      mortality. Fourteen days of treatment was more beneficial in delaying the time to
      death than treatment for seven days. Pathological findings in everolimus-treated
      mice showed reduced lung haemorrhage and lung weights in response to infection.
      CONCLUSIONS: These results provide proof of concept that cellular targets can be
      identified by gene knockout methods, and highlight the importance of the PI3K-AKT
      mTOR pathway in supporting viral infections.

PMID- 22374989
TI  - SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is
      antiarrhythmic.
AB  - AIMS: Reentry accounts for most life-threatening arrhythmias, complicating
      myocardial infarction, and therapies that consistently prevent reentry from
      occurring are lacking. In this study, we compare antiarrhythmic effects of gene
      transfer of green fluorescent protein (GFP; sham), the skeletal muscle sodium
      channel (SkM1), the liver-specific connexin (Cx32), and SkM1/Cx32 in the subacute
      canine infarct. METHODS AND RESULTS: Immediately after ligation of the left
      anterior descending artery, viral constructs were implanted in the epicardial
      border zone (EBZ). Five to 7 days later, efficient restoration of impulse
      propagation (narrow QRS and local electrogram duration) occurred in SkM1, Cx32,
      and SkM1/Cx32 groups (P< 0.05 vs. GFP). Programmed electrical stimulation from
      the EBZ induced sustained ventricular tachycardia (VT)/ventricular fibrillation
      (VF) in 15/22 GFP dogs vs. 2/12 SkM1, 6/14 Cx32, and 8/10 SkM1/Cx32 (P< 0.05 SkM1
      vs. GFP). GFP, SkM1, and SkM1/Cx32 had predominantly polymorphic VT/VF, whereas
      in Cx32 dogs, monomorphic VT predominated (P< 0.05 for Cx32 vs. GFP). Tetrazolium
      red staining showed significantly larger infarcts in Cx32- vs. GFP-treated
      animals (P< 0.05). CONCLUSION: Whereas SkM1 gene transfer reduces the incidence
      of inducible VT/VF, Cx32 therapy to improve gap junctional conductance results in
      larger infarct size, a different VT morphology, and no antiarrhythmic efficacy.

PMID- 22374992
TI  - Bigger, better, sooner--scaling up for success.
AB  - Over the last twenty years, the field of epidemiology has seen a rapidly
      increasing interest in, and need for, addressing low-level risks, interactions as
      well as main effects, and simultaneous assessment of vast numbers of biomarkers.
      Multiple examples over this time have shown the necessity for very large, high
      quality individual studies (e.g., biobanks) or consortia of studies for these
      efforts to be successful. The need for this will continue to increase in the
      foreseeable future. It will also be important to analyze and publish aggregated
      data much earlier in the discovery process than typical for past efforts.

PMID- 22374991
TI  - Gastric cancer incidence among Hispanics in California: patterns by time,
      nativity, and neighborhood characteristics.
AB  - BACKGROUND: Better understanding about gastric cancer incidence patterns among
      Hispanics by birthplace, socioeconomic status (SES), and acculturation can
      improve preventive strategies and disease models. METHODS: Incidence rates, rate
      ratios, and estimated annual percent change (EAPC) in rates of anatomic and
      histologic subtype-specific gastric cancer were calculated by age, sex, and
      nativity among Hispanics using California Cancer Registry data from 1988 through
      2004. Incidence rates in 1998 to 2002 were compared by neighborhood SES and
      Hispanic enclave status according to 2000 US Census data. RESULTS: Incidence
      rates of diffuse gastric cancer increased from 1988 through 2004 among foreign
      born Hispanic men (EAPC: 3.5%, 95% CI: 1.5%-5.5%) and U.S.-born Hispanic women
      (EAPC: 3.0%, 95% CI: 0.7%-5.3%). During the same time period, incidence rates of
      intestinal gastric cancer declined significantly and both cardia and noncardia
      gastric cancer were steady or declined among foreign-born and U.S.-born Hispanic
      men and women. Noncardia and both intestinal and diffuse gastric cancer were more
      common in foreign-born than U.S.-born Hispanic men and women, and in those from
      lower SES, higher enclave neighborhoods. By contrast, among younger and middle
      aged Hispanic men, cardia tumors were more common in the U.S.-born than the
      foreign-born, and in higher SES, lower enclave neighborhoods. CONCLUSIONS:
      Varying gastric cancer risk factors among Hispanic subgroups and increasing rates
      of diffuse gastric cancer in foreign-born Hispanic men and U.S.-born Hispanic
      women merit further investigation to identify separate disease etiologies.
      IMPACT: Age, sex, birthplace, SES, and acculturation modify gastric cancer
      incidence in Hispanics and should be considered when examining disease risk and
      prevention.

PMID- 22374993
TI  - Genetic polymorphisms in oxidative stress pathway genes and modification of BMI
      and risk of non-Hodgkin lymphoma.
AB  - BACKGROUND: Being overweight and obese increases oxidative stress in the body. To
      test the hypothesis that genetic variations in oxidative stress pathway genes
      modify the relationship between body mass index (BMI) and risk of non-Hodgkin
      lymphoma (NHL), we conducted a population-based case-control study in Connecticut
      women. METHODS: Individuals who were overweight/obese (BMI >= 25) were compared
      with normal and underweight individuals (BMI < 25), and their risk of NHL
      stratified assuming a dominant allele model for each oxidative stress pathway
      single-nucleotide polymorphism. RESULTS: Polymorphisms in AKR1A1, AKR1C1, AKR1C3,
      CYBA, GPX1, MPO, NCF2, NCF4, NOS1, NOS2A NOS3, OGG1, ATG9B, SOD1, SOD2, SOD3,
      RAC1, and RAC2 genes after false discovery rate adjustment did not modify the
      association between BMI and risk of NHL overall and histologic subtypes.
      CONCLUSIONS: The results suggest that common genetic variations in oxidative
      stress genes do not modify the relationship between BMI and risk of NHL. IMPACT:
      Studies of BMI and oxidative stress independently may elevate NHL risk, but this
      study suggests no interaction of the two risk factors. Future studies with larger
      study populations may reveal interactions.

PMID- 22374994
TI  - Effectiveness of hepatocellular carcinoma surveillance in patients with
      cirrhosis.
AB  - BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) is recommended in
      patients with cirrhosis, but the effectiveness of a surveillance program in
      clinical practice has yet to be established. AIMS: To evaluate the effectiveness
      of a surveillance program with ultrasound and alpha-fetoprotein (AFP) to detect
      early HCCs. METHODS: Four hundred and forty-six patients with Child A/B cirrhosis
      were prospectively enrolled between January 2004 and September 2006 and followed
      until July 2010. HCC surveillance using ultrasound and AFP was conducted per the
      treating hepatologist, although the standard was every 6 to 12 months. HCC was
      diagnosed using American Association for the Study of Liver Disease (AASLD)
      guidelines and early HCC defined by Barcelona Clinic Liver Cancer (BCLC) staging.
      Performance characteristics were determined for surveillance using AFP,
      ultrasound, or the combination. RESULTS: After a median follow-up of 3.5 years,
      41 patients developed HCCs, of whom 30 (73.2%) had early HCCs. The annual
      incidence of HCC was 2.8%, with cumulative 3- and 5-year incidence rates of 5.7%
      and 9.1%, respectively. Surveillance ultrasound and AFP had sensitivities of 44%
      and 66% and specificities of 92% and 91%, respectively, for the detection of
      HCCs. Sensitivity significantly improved to 90%, with minimal loss in specificity
      (83%) when these tests were used in combination. CONCLUSIONS: When used as a
      surveillance program in a real-world clinical setting, combination of ultrasound
      and AFP is the most effective strategy to detect HCC at an early stage. IMPACT:
      Our results differ from the guidelines of the AASLD.

PMID- 22374995
TI  - Added value of a serum proteomic signature in the diagnostic evaluation of lung
      nodules.
AB  - BACKGROUND: Current management of lung nodules is complicated by nontherapeutic
      resections and missed chances for cure. We hypothesized that a serum proteomic
      signature may add diagnostic information beyond that provided by combined
      clinical and radiographic data. METHODS: Cohort A included 265 and cohort B 114
      patients. Using multivariable logistic regression analysis we calculated the area
      under the receiver operating characteristic curve (AUC) and quantified the added
      value of a previously described serum proteomic signature beyond clinical and
      radiographic risk factors for predicting lung cancer using the integration
      discrimination improvement (IDI) index. RESULTS: The average computed tomography
      (CT) measured nodule size in cohorts A and B was 37.83 versus 23.15 mm among
      patients with lung cancer and 15.82 versus 17.18 mm among those without,
      respectively. In cohort A, the AUC increased from 0.68 to 0.86 after adding chest
      CT imaging variables to the clinical results, but the proteomic signature did not
      provide meaningful added value. In contrast, in cohort B, the AUC improved from
      0.46 with clinical data alone to 0.61 when combined with chest CT imaging data
      and to 0.69 after adding the proteomic signature (IDI of 20% P = 0.0003). In
      addition, in a subgroup of 100 nodules between 5 and 20 mm in diameter, the
      proteomic signature added value with an IDI of 15% (P <= 0.0001). CONCLUSIONS:
      The results show that this serum proteomic biomarker signature may add value to
      the clinical and chest CT evaluation of indeterminate lung nodules. IMPACT: This
      study suggests a possible role of a blood biomarker in the evaluation of
      indeterminate lung nodules.

PMID- 22374996
TI  - Crystal structure of binary and ternary complexes of archaeal UDP-galactose 4
      epimerase-like L-threonine dehydrogenase from Thermoplasma volcanium.
AB  - A gene from the thermophilic archaeon Thermoplasma volcanium encoding an L
      threonine dehydrogenase (L-ThrDH) with a predicted amino acid sequence that was
      remarkably similar to the sequence of UDP-galactose 4-epimerase (GalE) was
      overexpressed in Escherichia coli, and its product was purified and
      characterized. The expressed enzyme was moderately thermostable, retaining more
      than 90% of its activity after incubation for 10 min at up to 70  degrees C. The
      catalytic residue was assessed using site-directed mutagenesis, and Tyr(137) was
      found to be essential for catalysis. To clarify the structural basis of the
      catalytic mechanism, four different crystal structures were determined using the
      molecular replacement method: L-ThrDH-NAD(+), L-ThrDH in complex with NAD(+) and
      pyruvate, Y137F mutant in complex with NAD(+) and L-threonine, and Y137F in
      complex with NAD(+) and L-3-hydroxynorvaline. Each monomer consisted of a
      Rossmann-fold domain and a C-terminal catalytic domain, and the fold of the
      catalytic domain showed notable similarity to that of the GalE-like L-ThrDH from
      the psychrophilic bacterium Flavobacterium frigidimaris KUC-1. The substrate
      binding model suggests that the reaction proceeds through abstraction of the beta
      hydroxyl hydrogen of L-threonine via direct proton transfer driven by Tyr(137).
      The factors contributing to the thermostability of T. volcanium L-ThrDH were
      analyzed by comparing its structure to that of F. frigidimaris L-ThrDH. This
      comparison showed that the presence of extensive inter- and intrasubunit ion pair
      networks are likely responsible for the thermostability of T. volcanium L-ThrDH.
      This is the first description of the molecular basis for the substrate
      recognition and thermostability of a GalE-like L-ThrDH.

PMID- 22374997
TI  - Turning receptors on and off with intracellular pepducins: new insights into G
      protein-coupled receptor drug development.
AB  - G-protein-coupled receptors (GPCRs) are a large family of remarkably versatile
      membrane proteins that are attractive therapeutic targets because of their
      involvement in a vast range of normal physiological processes and pathological
      diseases. Upon activation, intracellular domains of GPCRs mediate signaling to G
      proteins, but these domains have yet to be effectively exploited as drug targets.
      Cell-penetrating lipidated peptides called pepducins target specific
      intracellular loops of GPCRs and have recently emerged as effective allosteric
      modulators of GPCR activity. The lipid moiety facilitates translocation across
      the plasma membrane, where pepducins then specifically modulate signaling of
      their cognate receptor. To date, pepducins and related lipopeptides have been
      shown to specifically modulate the activity of diverse GPCRs and other membrane
      proteins, including protease-activated receptors (PAR1, PAR2, and PAR4),
      chemokine receptors (CXCR1, CXCR2, and CXCR4), sphingosine 1-phosphate receptor-3
      (S1P3), the melanocortin-4 receptor, the Smoothened receptor, formyl peptide
      receptor-2 (FPR2), the relaxin receptor (LGR7), G-proteins (Galpha(q/11/o/13)),
      muscarinic acetylcholine receptor and vanilloid (TRPV1) channels, and the GPIIb
      integrin. This minireview describes recent advances made using pepducin
      technology in targeting diverse GPCRs and the use of pepducins in identifying
      potential novel drug targets.

PMID- 22374998
TI  - Molecular imprint of enzyme active site by camel nanobodies: rapid and efficient
      approach to produce abzymes with alliinase activity.
AB  - Screening of inhibitory Ab1 antibodies is a critical step for producing catalytic
      antibodies in the anti-idiotypic approach. However, the incompatible surface of
      the active site of the enzyme and the antigen-binding site of heterotetrameric
      conventional antibodies become the limiting step. Because camelid-derived
      nanobodies possess the potential to preferentially bind to the active site of
      enzymes due to their small size and long CDR3, we have developed a novel approach
      to produce antibodies with alliinase activities by exploiting the molecular
      mimicry of camel nanobodies. By screening the camelid-derived variable region of
      the heavy chain cDNA phage display library with alliinase, we obtained an
      inhibitory nanobody VHHA4 that recognizes the active site. Further screening with
      VHHA4 from the same variable domain of the heavy chain of a heavy-chain antibody
      library led to a higher incidence of anti-idiotypic Ab2 abzymes with alliinase
      activities. One of the abzymes, VHHC10, showed the highest activity that can be
      inhibited by Ab1 VHHA4 and alliinase competitive inhibitor penicillamine and
      significantly suppressed the B16 tumor cell growth in the presence of alliin in
      vitro. The results highlight the feasibility of producing abzymes via anti
      idiotypic nanobody approach.

PMID- 22374999
TI  - Misses during water oxidation in photosystem II are S state-dependent.
AB  - The period of four oscillation of the S state intermediates of the water
      oxidizing complex in Photosystem II (PSII) is commonly analyzed by the Kok
      parameters. The important miss factor determines the efficiency for each S
      transition. Commonly, an equal miss factor has been used in the analysis. We have
      used EPR signals which probe all S states in the same sample during S cycle
      advancement. This allows, for the first time, to measure directly the miss
      parameter for each S state transition. Experiments were performed in PSII
      membrane preparations from spinach in the presence of electron acceptor at 1 
      degrees C and 20  degrees C. The data show that the miss parameter is different
      in different transitions and shows different temperature dependence. We found no
      misses at 1  degrees C and 10% misses at 20  degrees C during the S(1)->S(2)
      transition. The highest miss factor was found in the S(2)->S(3) transition which
      decreased from 23% to 16% with increasing temperature. For the S(3)->S(0)
      transition the miss parameter was found to be 7% at 1  degrees C and decreased to
      3% at 20  degrees C. For the S(0)->S(1) transition the miss parameter was found
      to be approximately 10% at both temperatures. The contribution from the acceptor
      side in the form of recombination reactions as well as from the donor side of
      PSII to the uneven misses is discussed. It is suggested that the different
      transition efficiency in each S transition partly reflects the chemistry at the
      CaMn(4)O(5) cluster. That consequently contributes to the uneven misses during S
      cycle turnover in PSII.

PMID- 22375000
TI  - GRK2 protein-mediated transphosphorylation contributes to loss of function of MU
      opioid receptors induced by neuropeptide FF (NPFF2) receptors.
AB  - Neuropeptide FF (NPFF) interacts with specific receptors to modulate opioid
      functions in the central nervous system. On dissociated neurons and neuroblastoma
      cells (SH-SY5Y) transfected with NPFF receptors, NPFF acts as a functional
      antagonist of MU-opioid (MOP) receptors by attenuating the opioid-induced
      inhibition of calcium conductance. In the SH-SY5Y model, MOP and NPFF(2)
      receptors have been shown to heteromerize. To understand the molecular mechanism
      involved in the anti-opioid activity of NPFF, we have investigated the
      phosphorylation status of the MOP receptor using phospho-specific antibody and
      mass spectrometry. Similarly to direct opioid receptor stimulation, activation of
      the NPFF(2) receptor by [D-Tyr-1-(NMe)Phe-3]NPFF (1DMe), an analog of NPFF,
      induced the phosphorylation of Ser-377 of the human MOP receptor. This
      heterologous phosphorylation was unaffected by inhibition of second messenger
      dependent kinases and, contrarily to homologous phosphorylation, was prevented by
      inactivation of G(i/o) proteins by pertussis toxin. Using siRNA knockdown we
      could demonstrate that 1DMe-induced Ser-377 cross-phosphorylation and MOP
      receptor loss of function were mediated by the G protein receptor kinase GRK2. In
      addition, mass spectrometric analysis revealed that the phosphorylation pattern
      of MOP receptors was qualitatively similar after treatment with the MOP agonist
      Tyr-D-Ala-Gly (NMe)-Phe-Gly-ol (DAMGO) or after treatment with the NPFF agonist
      1DMe, but the level of multiple phosphorylation was more intense after DAMGO.
      Finally, NPFF(2) receptor activation was sufficient to recruit beta-arrestin2 to
      the MOP receptor but not to induce its internalization. These data show that NPFF
      induced heterologous desensitization of MOP receptor signaling is mediated by
      GRK2 and could involve transphosphorylation within the heteromeric receptor
      complex.

PMID- 22375001
TI  - Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific
      binding sites that mediate direct interactions with scaffold protein PSD-95.
AB  - N-methyl-D-aspartate (NMDA) neurotransmitter receptors and the postsynaptic
      density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of
      scaffolding proteins are integral components of post-synaptic macromolecular
      signaling complexes that serve to propagate glutamate responses intracellularly.
      Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a
      conserved ES(E/D)V amino acid sequence located at their C termini. We previously
      challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in
      both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co
      immunoprecipitations from transfected mammalian cells, yeast two-hybrid
      interaction assays, and glutathione S-transferase (GST) pulldown assays, we show
      that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif
      and additionally via an Src homology 3 domain-binding motif that associates with
      the Src homology 3 domain of PSD-95. Peptide inhibition of co
      immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non
      ESDV sites are required for association in native brain tissue. Furthermore, we
      refine the non-ESDV site within NR2B to residues 1149-1157. These findings
      provide a molecular basis for the differential association of NMDA receptor
      subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may
      contribute to the organization, lateral mobility, and ultimately the function of
      NMDA receptor subtypes at synapses. Furthermore, they provide a more general
      molecular mechanism by which the scaffold, PSD-95, may discriminate between
      potential interacting partner proteins.

PMID- 22375002
TI  - Protein implicated in nonsyndromic mental retardation regulates protein kinase A
      (PKA) activity.
AB  - Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which
      encodes a C2 domain and DM14 domain-containing protein, has been linked to severe
      autosomal recessive nonsyndromic mental retardation. Using a mouse model that
      produces a truncated form of CC2D1A that lacks the C2 domain and three of the
      four DM14 domains, we show that CC2D1A is important for neuronal differentiation
      and brain development. CC2D1A mutant neurons are hypersensitive to stress and
      have a reduced capacity to form dendrites and synapses in culture. At the
      biochemical level, CC2D1A transduces signals to the cyclic adenosine 3',5'
      monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell
      differentiation. PKA activity is compromised, and the translocation of its
      catalytic subunit to the nucleus is also defective in CC2D1A mutant cells.
      Consistently, phosphorylation of the PKA target cAMP-responsive element-binding
      protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects
      in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal
      primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP
      PKA complex following forskolin treatment and accumulates in vesicles or on the
      plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA
      complex to the membrane to facilitate signal transduction. Together, our data
      show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway,
      which may be the underlying cause for impaired mental function in nonsyndromic
      mental retardation patients with CC2D1A mutation.

PMID- 22375003
TI  - Hindgut innate immunity and regulation of fecal microbiota through melanization
      in insects.
AB  - Many insects eat the green leaves of plants but excrete black feces in an as yet
      unknown mechanism. Insects cannot avoid ingesting pathogens with food that will
      be specifically detected by the midgut immune system. However, just as in
      mammals, many pathogens can still escape the insect midgut immune system and
      arrive in the hindgut, where they are excreted out with the feces. Here we show
      that the melanization of hindgut content induced by prophenoloxidase, a key
      enzyme that induces the production of melanin around invaders and at wound sites,
      is the last line of immune defense to clear bacteria before feces excretion. We
      used the silkworm Bombyx mori as a model and found that prophenoloxidase produced
      by hindgut cells is secreted into the hindgut contents. Several experiments were
      done to clearly demonstrate that the blackening of the insect feces was due to
      activated phenoloxidase, which served to regulate the number of bacteria in the
      hindgut. Our analysis of the silkworm hindgut prophenoloxidase discloses the
      natural secret of why the phytophagous insect feces is black and provides insight
      into hindgut innate immunity, which is still rather unclear in mammals.

PMID- 22375004
TI  - Structural domains required for Caenorhabditis elegans G protein-coupled receptor
      kinase 2 (GRK-2) function in vivo.
AB  - G protein-coupled receptor kinases (GRKs) are key regulators of signal
      transduction that specifically phosphorylate activated G protein-coupled
      receptors (GPCRs) to terminate signaling. Biochemical and crystallographic
      studies have provided great insight into mammalian GRK2/3 interactions and
      structure. However, despite extensive in vitro characterization, little is known
      about the in vivo contribution of these described GRK structural domains and
      interactions to proper GRK function in signal regulation. We took advantage of
      the disrupted chemosensory behavior characteristic of Caenorhabditis elegans grk
      2 mutants to discern the interactions required for proper in vivo Ce-GRK-2
      function. Informed by mammalian crystallographic and biochemical data, we
      introduced amino acid substitutions into the Ce-grk-2 coding sequence that are
      predicted to selectively disrupt GPCR phosphorylation, Galpha(q/11) binding,
      Gbetagamma binding, or phospholipid binding. Changing the most amino-terminal
      residues, which have been shown in mammalian systems to be required specifically
      for GPCR phosphorylation but not phosphorylation of alternative substrates or
      recruitment to activated GPCRs, eliminated the ability of Ce-GRK-2 to restore
      chemosensory signaling. Disrupting interaction between the predicted Ce-GRK-2
      amino-terminal alpha-helix and kinase domain, posited to stabilize GRKs in their
      active ATP- and GPCR-bound conformation, also eliminated Ce-GRK-2 chemosensory
      function. Finally, although changing residues within the RH domain, predicted to
      disrupt interaction with Galpha(q/11), did not affect Ce-GRK-2 chemosensory
      function, disruption of the predicted PH domain-mediated interactions with
      Gbetagamma and phospholipids revealed that both contribute to Ce-GRK-2 function
      in vivo. Combined, we have demonstrated functional roles for broadly conserved
      GRK2/3 structural domains in the in vivo regulation of organismal behavior.

PMID- 22375005
TI  - MarR-type transcriptional regulator ChlR activates expression of tetrapyrrole
      biosynthesis genes in response to low-oxygen conditions in cyanobacteria.
AB  - Oxygen is required for three enzyme reactions in chlorophyll and bilin
      biosynthesis pathways: coproporphyrinogen III oxidase (HemF), heme oxygenase
      (HO1), and Mg-protoporphyrin IX monomethylester cyclase (ChlA(I)). The
      cyanobacterium Synechocystis sp. PCC 6803 has alternative enzymes, HemN, HO2, and
      ChlA(II), to supply chlorophyll/bilins even under low-oxygen environments. The
      three genes form an operon, chlA(II)-ho2-hemN, that is induced in response to low
      oxygen conditions to bypass the oxygen-dependent reactions. Here we identified a
      transcriptional regulator for the induction of the operon in response to low
      oxygen conditions. A pseudorevertant, Deltaho1R, was isolated from a HO1-lacking
      mutant Deltaho1 that is lethal under aerobic conditions. Deltaho1R grew well even
      under aerobic conditions. In Deltaho1R, HO2 that is induced only under low-oxygen
      conditions was anomalously expressed under aerobic conditions to complement the
      loss of HO1. A G-to-C transversion in sll1512 causing the amino acid change from
      aspartate 35 to histidine was identified as the relevant mutation by resequencing
      of the Deltaho1R genome. Sll1512 is a MarR-type transcriptional regulator. An
      sll1512-lacking mutant grew poorly under low-oxygen conditions with a remarked
      decrease in Chl content that would be caused by the suppressed induction of the
      chlA(II) and hemN genes in Chl biosynthesis under low-oxygen conditions. These
      results demonstrated that Sll1512 is an activator in response to low-oxygen
      environments and that the D35H variant becomes a constitutive activator. This
      hypothesis was supported by a gel shift assay showing that the Sll1512-D35H
      variant binds to the DNA fragment upstream of the operon. We propose to name
      sll1512 chlR.

PMID- 22375006
TI  - Methyl CpG-binding protein isoform MeCP2_e2 is dispensable for Rett syndrome
      phenotypes but essential for embryo viability and placenta development.
AB  - Methyl CpG-binding protein 2 gene (MeCP2) mutations are implicated in Rett
      syndrome (RTT), one of the common causes of female mental retardation. Two MeCP2
      isoforms have been reported: MeCP2_e2 (splicing of all four exons) and MeCP2_e1
      (alternative splicing of exons 1, 3, and 4). Their relative expression levels
      vary among tissues, with MeCP2_e1 being more dominant in adult brain, whereas
      MeCP2_e2 is expressed more abundantly in placenta, liver, and skeletal muscle. In
      this study, we performed specific disruption of the MeCP2_e2-defining exon 2
      using the Cre-loxP system and examined the consequences of selective loss of
      MeCP2_e2 function in vivo. We performed behavior evaluation, gene expression
      analysis, using RT-PCR and real-time quantitative PCR, and histological analysis.
      We demonstrate that selective deletion of MeCP2_e2 does not result in RTT
      associated neurological phenotypes but confers a survival disadvantage to embryos
      carrying a MeCP2_e2 null allele of maternal origin. In addition, we reveal a
      specific requirement for MeCP2_e2 function in extraembryonic tissue, where
      selective loss of MeCP2_e2 results in placenta defects and up-regulation of peg
      1, as determined by the parental origin of the mutant allele. Taken together, our
      findings suggest a novel role for MeCP2 in normal placenta development and
      illustrate how paternal X chromosome inactivation in extraembryonic tissues
      confers a survival disadvantage for carriers of a mutant maternal MeCP2_e2
      allele. Moreover, our findings provide an explanation for the absence of reports
      on MeCP2_e2-specific exon 2 mutations in RTT. MeCP2_e2 mutations in humans may
      result in a phenotype that evades a diagnosis of RTT.

PMID- 22375008
TI  - JMJD5, a Jumonji C (JmjC) domain-containing protein, negatively regulates
      osteoclastogenesis by facilitating NFATc1 protein degradation.
AB  - Osteoclastogenesis is a highly regulated process governed by diverse classes of
      regulators. Among them, nuclear factor of activated T-cells calcineurin-dependent
      1 (NFATc1) is the primary osteoclastogenic transcription factor, and its
      expression is transcriptionally induced during early osteoclastogenesis by
      receptor activation of nuclear factor kappaB ligand (RANKL), an osteoclastogenic
      cytokine. Here, we report the novel enzymatic function of JMJD5, which regulates
      NFATc1 protein stability. Among the tested Jumonji C (JmjC) domain-containing
      proteins, decreased mRNA expression levels during osteoclastogenesis were found
      for JMJD5 in RAW264 cells stimulated by RANKL. To examine the functional role of
      JMJD5 in osteoclast differentiation, we established stable JMJD5 knockdown cells,
      and osteoclast formation was assessed. Down-regulated expression of JMJD5 led to
      accelerated osteoclast formation together with induction of several osteoclast
      specific genes such as Ctsk and DC-STAMP, suggesting that JMJD5 is a negative
      regulator in osteoclast differentiation. Although JMJD5 was recently reported as
      a histone demethylase for histone H3K36me2, no histone demethylase activity was
      detected in JMJD5 in vitro or in living cells, even for other methylated histone
      residues. Instead, JMJD5 co-repressed transcriptional activity by destabilizing
      NFATc1 protein. Protein hydroxylase activity mediated by the JmjC domain in JMJD5
      was required for the observed functions of JMJD5. JMJD5 induced the association
      of hydroxylated NFATc1 with the E3 ubiquitin ligase Von Hippel-Lindau tumor
      suppressor (VHL), thereby presumably facilitating proteasomal degradation of
      NFATc1 via ubiquitination. Taken together, the present study demonstrated that
      JMJD5 is a post-translational co-repressor for NFATc1 that attenuates
      osteoclastogenesis.

PMID- 22375007
TI  - Deregulated hepatic metabolism exacerbates impaired testosterone production in
      Mrp4-deficient mice.
AB  - The physiological role of multidrug resistance protein 4 (Mrp4, Abcc4) in the
      testes is unknown. We found that Mrp4 is expressed primarily in mouse and human
      Leydig cells; however, there is no current evidence that Mrp4 regulates
      testosterone production. We investigated its role in Leydig cells, where
      testosterone production is regulated by cAMP, an intracellular messenger formed
      when the luteinizing hormone (LH) receptor is activated. Because Mrp4 regulates
      cAMP, we compared testosterone levels in Mrp4(-/-) and Mrp4(+/+) mice. Young
      Mrp4(-/-) mice had significantly impaired gametogenesis, reduced testicular
      testosterone, and disruption of Leydig cell cAMP homeostasis. Both young and
      adult mice had impaired testosterone production. In Mrp4(-/-) primary Leydig
      cells treated with LH, intracellular cAMP production was impaired and cAMP
      response element-binding protein (CREB) phosphorylation was strongly attenuated.
      Notably, expression of CREB target genes that regulate testosterone biosynthesis
      was reduced in Mrp4(-/-) Leydig cells in vivo. Therefore, Mrp4 is required for
      normal Leydig cell testosterone production. However, adult Mrp4(-/-) mice are
      fertile, with a normal circulating testosterone concentration. The difference is
      that in 3-week-old Mrp4(-/-) mice, disruption of gonadal testosterone production
      up-regulates hepatic Cyp2b10, a known testosterone-metabolizing enzyme.
      Therefore, defective testicular testosterone production de-regulates hepatic Cyp
      mediated testosterone metabolism to disrupt gametogenesis. These findings have
      important implications for understanding the side effects of therapeutics that
      disrupt Mrp4 function and are reported to alter androgen production.

PMID- 22375009
TI  - Caspar-like gene depletion reduces Leishmania infection in sand fly host
      Lutzomyia longipalpis.
AB  - Female phlebotomine sand flies Lutzomyia longipalpis naturally harbor populations
      of the medically important Leishmania infantum (syn. Leishmania chagasi) parasite
      in the gut, but the extent to which the parasite interacts with the immune system
      of the insect vector is unknown. To investigate the sand fly immune response and
      its interaction with the Leishmania parasite, we identified a homologue for
      caspar, a negative regulator of immune deficiency signaling pathway. We found
      that feeding antibiotics to adult female L. longipalpis resulted in an up
      regulation of caspar expression relative to controls. caspar was differentially
      expressed when females were fed on gram-negative and gram-positive bacterial
      species. caspar expression was significantly down-regulated in females between 3
      and 6 days after a blood feed containing Leishmania mexicana amastigotes. RNA
      interference was used to deplete caspar expression in female L. longipalpis,
      which were subsequently fed with Leishmania in a blood meal. Sand fly gut
      populations of both L. mexicana and L. infantum were significantly reduced in
      caspar-depleted females. The prevalence of L. infantum infection in the females
      fell from 85 to 45%. Our results provide the first insight into the operation of
      immune homeostasis in phlebotomine sand flies during the growth of bacterial and
      Leishmania populations in the digestive tract. We have demonstrated that the
      activation of the sand fly immune system, via depletion of a single gene, can
      lead to the abortion of Leishmania development and the disruption of transmission
      by the phlebotomine sand fly.

PMID- 22375010
TI  - Kruppel-like factor 11 differentially couples to histone acetyltransferase and
      histone methyltransferase chromatin remodeling pathways to transcriptionally
      regulate dopamine D2 receptor in neuronal cells.
AB  - The importance of Kruppel-like factor (KLF)-mediated transcriptional pathways in
      the biochemistry of neuronal differentiation has been recognized relatively
      recently. Elegant studies have revealed that KLF proteins are important
      regulators of two major molecular and cellular processes critical for neuronal
      cell differentiation: neurite formation and the expression of neurotransmitter
      related genes. However, whether KLF proteins mediate these key processes in a
      separate or coordinated fashion remains unknown. Moreover, knowledge on the
      contribution of chromatin dynamics to the biochemical mechanisms utilized by
      these proteins to perform their function is absent. Here we report the
      characterization of two antagonistic, chromatin-mediated mechanisms by which
      KLF11, also known as TIEG2 (transforming growth factor-beta-inducible early gene
      2) and MODY VII (maturity onset diabetes of the young VII), regulates
      transcription of the fopamine D2 receptor (Drd2) gene. First, KLF11 activates
      transcription by binding to a distinct Sp-KLF site within the Drd2 promoter (-98
      to -94) and recruiting the p300 histone acetyltransferase. Second, Drd2
      transcriptional activation is partially antagonized by heterochromatin protein 1
      (HP1), the code reader for histone H3 lysine 9 methylation. Interestingly, KLF11
      regulates neurotransmitter receptor gene expression in differentiating neuronal
      cell populations without affecting neurite formation. Overall, these studies
      highlight histone methylation and acetylation as key biochemical mechanisms
      modulating KLF-mediated neurotransmitter gene transcription. These data extend
      our knowledge of chromatin-mediated biochemical events that maintain key
      phenotypic features of differentiated neuronal cells.

PMID- 22375011
TI  - Diabody mixture providing full protection against experimental scorpion
      envenoming with crude Androctonus australis venom.
AB  - Androctonus australis is primarily involved in envenomations in North Africa,
      notably in Tunisia and Algeria, and constitutes a significant public health
      problem in this region. The toxicity of the venom is mainly due to various
      neurotoxins that belong to two distinct structural and immunological groups,
      group I (the AahI and AahIII toxins) and group II (AahII). Here, we report the
      use of a diabody mixture in which the molar ratio matches the characteristics of
      toxins and polymorphism of the venom. The mixture consists of the Db9C2 diabody
      (anti-group I) and the Db4C1op diabody (anti-AahII), the latter being modified to
      facilitate in vitro production and purification. The effectiveness of the
      antivenom was tested in vivo under conditions simulating scorpion envenomation.
      The intraperitoneal injection of 30 MUg of the diabody mixture protected almost
      all the mice exposed to 3 LD(50) s.c. of venom. We also show that the presence of
      both diabodies is necessary for the animals to survive. Our results are the first
      demonstration of the strong protective power of small quantities of antivenom
      used in the context of severe envenomation with crude venom.

PMID- 22375012
TI  - Native mutant huntingtin in human brain: evidence for prevalence of full-length
      monomer.
AB  - Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of
      huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and
      Western blot reveals htt as full-length and fragmented. Here we used Blue Native
      PAGE (BNP) and Western blots to study native htt in human postmortem brain.
      Antisera against htt detected a single band broadly migrating at 575-850 kDa in
      control brain and at 650-885 kDa in heterozygous and Venezuelan homozygous HD
      brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain.
      There was little htt cleavage even if lysates were pretreated with trypsin,
      indicating a property of native htt to resist protease cleavage. A soluble mutant
      htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1
      17)) and increased when lysates were treated with denaturants (SDS, 8 M urea,
      DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants.
      Based on migration of in vitro translated htt fragments, the 180-kDa segment
      terminated ~htt 670-880 amino acids. If second dimension SDS-PAGE followed BNP,
      the 180-kDa mutant htt was absent, and 43-50 kDa htt fragments appeared. Brain
      lysates from two HD mouse models expressed native full-length htt; a mutant
      fragment formed if lysates were pretreated with 8 M urea + DTT. Native full
      length mutant htt in embryonic HD(140Q/140Q) mouse primary neurons was intact
      during cell death and when cell lysates were exposed to denaturants before BNP.
      Thus, native mutant htt occurs in brain and primary neurons as a soluble full
      length monomer.

PMID- 22375013
TI  - Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in
      homologous DNA repair.
AB  - Homologous recombination catalyzed by the RAD51 recombinase is essential for
      maintaining genome integrity upon the induction of DNA double strand breaks and
      other DNA lesions. By enhancing the recombinase activity of RAD51, RAD51AP1
      (RAD51-associated protein 1) serves a key role in homologous recombination
      mediated chromosome damage repair. We show here that RAD51AP1 harbors two
      distinct DNA binding domains that are both needed for maximal protein activity
      under physiological conditions. We have finely mapped the two DNA binding domains
      in RAD51AP1 and generated mutant variants that are impaired in either or both of
      the DNA binding domains. Examination of these mutants reveals that both domains
      are indispensable for RAD51AP1 function in cells. These and other results
      illuminate the mechanistic basis of RAD51AP1 action in homologous DNA repair.

PMID- 22375014
TI  - Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by
      topoisomerases I and II and base alkylation in vertebrate cells.
AB  - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes
      (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin
      induced DNA damage by hydrolyzing 3'-phosphoglycolates. Yeast Tdp1 has also been
      implicated in the repair of topoisomerase II-DNA cleavage complexes (Top2cc). To
      determine whether vertebrate Tdp1 is involved in the repair of various DNA end
      blocking lesions, we generated Tdp1 knock-out cells in chicken DT40 cells (Tdp1-/
      ) and Tdp1-complemented DT40 cells with human TDP1. We found that Tdp1-/- cells
      were not only hypersensitive to camptothecin and bleomycin but also to etoposide,
      methyl methanesulfonate (MMS), H(2)O(2), and ionizing radiation. We also show
      they were deficient in mitochondrial Tdp1 activity. In biochemical assays,
      recombinant human TDP1 was found to process 5'-phosphotyrosyl DNA ends when they
      mimic the 5'-overhangs of Top2cc. Tdp1 also processes 3'-deoxyribose phosphates
      generated from hydrolysis of abasic sites, which is consistent with the
      hypersensitivity of Tdp1-/- cells to MMS and H(2)O(2). Because recent studies
      established that CtIP together with BRCA1 also repairs topoisomerase-mediated DNA
      damage, we generated dual Tdp1-CtIP-deficient DT40 cells. Our results show that
      Tdp1 and CtIP act in parallel pathways for the repair of Top1cc and MMS-induced
      lesions but are epistatic for Top2cc. Together, our findings reveal a broad
      involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the
      repair of Top2-induced DNA damage.

PMID- 22375015
TI  - Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559,
      and 807.
AB  - Colony-stimulating factor-1 (CSF-1)-stimulated CSF-1 receptor (CSF-1R) tyrosine
      phosphorylation initiates survival, proliferation, and differentiation signaling
      pathways in macrophages. Either activation loop Y807F or juxtamembrane domain
      (JMD) Y559F mutations severely compromise CSF-1-regulated proliferation and
      differentiation. YEF, a CSF-1R in which all eight tyrosines phosphorylated in the
      activated receptor were mutated to phenylalanine, lacks in vitro kinase activity
      and in vivo CSF-1-regulated tyrosine phosphorylation. The addition of Tyr-807
      alone to the YEF backbone (Y807AB) led to CSF-1-independent but receptor kinase
      dependent proliferation, without detectable activation loop Tyr-807
      phosphorylation. The addition of Tyr-559 alone (Y559AB) supported a low level of
      CSF-1-independent proliferation that was slightly enhanced by CSF-1, indicating
      that Tyr-559 has a positive Tyr-807-independent effect. Consistent with the
      postulated autoinhibitory role of the JMD Tyr-559 and its relief by ligand
      induced Tyr-559 phosphorylation, the addition of Tyr-559 to the Y807AB background
      suppressed proliferation in the absence of CSF-1, but restored most of the CSF-1
      stimulated proliferation. Full restoration of kinase activation and proliferation
      required the additional add back of JMD Tyr-544. Inhibitor experiments indicate
      that the constitutive proliferation of Y807AB macrophages is mediated by the
      phosphatidylinositol 3-kinase (PI3K) and ERK1/2 pathways, whereas proliferation
      of WT and Y559,807AB macrophages is, in addition, contributed to by Src family
      kinase (SFK)-dependent pathways. Thus Tyr-807 confers sufficient kinase activity
      for strong CSF-1-independent proliferation, whereas Tyr-559 maintains the
      receptor in an inactive state. Tyr-559 phosphorylation releases this restraint
      and may also contribute to the CSF-1-regulated proliferative response by
      activating Src family kinase.

PMID- 22375016
TI  - Organization of the human inferior parietal lobule based on receptor
      architectonics.
AB  - Human inferior parietal lobule (IPL) plays a key role in various cognitive
      functions. Its functional diversity, including attention, language, and action
      processing, is reflected by its structural segregation into 7
      cytoarchitectonically distinct areas, each with characteristic connectivity
      patterns. We hypothesized that commonalities of the cytoarchitectonic,
      connectional, and functional diversity of the IPL should be reflected by a
      correlated transmitter receptor-based organization. Since the function of a
      cortical area requires a well-tuned receptor balance, the densities of 15
      different receptors were measured in each IPL area. A hierarchical cluster
      analysis of the receptor balance revealed a tripartite segregation of the IPL
      into a rostral, middle, and caudal group. Comparison with other cortical areas
      showed strong similarities with Broca's region for all 3 groups, with the
      superior parietal cortex for the middle, and with extrastriate visual areas for
      the caudal group. Notably, caudal-most area PGp has a receptor fingerprint very
      similar to that of ventral extrastriate visual cortex. We therefore propose a new
      organizational model of the human IPL, consisting of 3 clusters, which
      corresponds to its known cytoarchitectonic, connectional, and functional
      diversity at the molecular level. This might reflect a general organizational
      principle of human IPL, beyond specific functional domains.

PMID- 22375018
TI  - Mechanotransduction is enhanced by the synergistic action of heterotypic cell
      interactions and TGF-beta1.
AB  - With the use of planar substrates and collagen gels, the field of
      mechanotransduction has focused on the role of extracellular matrix stiffness,
      mechanical tension, and TGF-beta1 in generating a more contractile fibroblast.
      However, little is known about the role of cell-cell interactions in inducing
      cellular contraction. We used 3-dimensional self-assembled microtissues, in which
      cell-cell interactions dominate, and a recently developed cell power assay (an
      assay for mechanotransduction) to quantify the effects of TGF-beta1 vs. the
      heterotypic cell interface on the power exerted by pure normal human fibroblast
      (NHF) and pure rat hepatocyte 35 (H35) microtissues and their mixes. As a
      control, we found that TGF-beta1 only doubled the power output of pure NHF and
      pure H35 microtissues, whereas the heterotypic environment resulted in a 5-fold
      increase in cell power (0.24+/-0.05 to 1.17+/-0.13 fJ/h). Seeding TGF-beta1
      treated NHFs with untreated H35 cells demonstrated that the heterotypic
      environment and TGF-beta1 synergistically increase cell power by 22* by
      maximizing heterotypic cell interactions. Using a mathematical simulation of
      stress generation, we showed that tensile forces can be enhanced by heterotypic
      cell interactions. These data render a new understanding of how heterotypic cell
      interactions may increase cellular force generation during wound healing.

PMID- 22375017
TI  - Rapid down-regulation of gammac on T cells in early SIV infection correlates with
      impairment of T-cell function.
AB  - The common gamma(c) subunit molecule is shared among all gamma(c) cytokines and
      clearly involved in T-cell function, but its role in HIV infection and immunity
      is not well understood. Here, we examined expression and function of gamma(c) on
      T cells during SIV infection in Rhesus macaques. Surface gamma(c) distribution
      was differentially expressed on CD4(+) and CD8(+) T cells, and CD4(+)
      naive/memory cell populations in various lymphoid tissues of normal macaques.
      However, surface gamma(c) expression was rapidly and significantly down-regulated
      on T cells in acute infection with pathogenic SIV, compared to infection with a
      less virulent SHIV or controls and did not recover on CD8(+) T cells in the
      chronic stage. Moreover, the peripheral and CD4(+)T cell loss was inversely
      correlated with gamma(c)(+) CD8(+) T cells in individual tissues. gamma(c)(+) T
      cells were mainly functional as evidenced by higher cytokine secretion and
      proliferative capacity. Further in vitro experiments found that surface gamma(c)
      expression could be down-regulated following high level of IL-7 treatment by both
      internalization and shedding. Down-regulation of gamma(c) during early HIV/SIV
      infection may inhibit T-cell function, particularly of CD8(+) T cells, and, may
      be linked with immune failure and loss of viral containment.

PMID- 22375020
TI  - Demographics, clinical characteristics and outcomes of neonates diagnosed with
      fetomaternal haemorrhage.
AB  - OBJECTIVE: To determine clinical characteristics, demographics and short-term
      outcomes of neonates diagnosed with fetomaternal haemorrhage (FMH). DESIGN: The
      authors analysed the Nationwide Inpatient Sample, 1993 to 2008. Singleton births
      diagnosed with FMH were identified by International Classification of Diseases
      (ICD-9) code 762.3. Descriptive, univariate and multivariable regression analyses
      were performed to determine the national annual incidence of FMH over time as
      well as demographics and clinical characteristics of neonates with FMH. RESULTS:
      FMH was identified in 12 116 singleton births. Newborns with FMH required high
      intensity of care: 26.3% received mechanical ventilation, 22.4% received blood
      product transfusion and 27.8% underwent central line placement. Preterm birth (OR
      3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk
      factors for FMH. Higher patient income was associated with increased likelihood
      of FMH diagnosis (OR 1.2), and Whites were more likely to be diagnosed than
      ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the
      Southern USA (OR 0.8 vs the Northeastern USA). CONCLUSIONS: Diagnosis of FMH is
      associated with significant morbidity as well as regional, socioeconomic and
      racial disparity. Further study is needed to distinguish between diagnostic
      coding bias and true epidemiology of the disease. This is the first report of
      socioeconomic and racial/ethnic disparities in FMH, which may represent
      disparities in detection that require national attention.

PMID- 22375021
TI  - Patent ductus arteriosus: time to grasp the nettle?
AB  - The management of patent ductus arteriosus is controversial, and there are
      diverse approaches to treatment, ranging from very conservative management
      through to early and aggressive securing of ductus closure, either
      pharmacologically or surgically. This lack of consensus on best management
      reflects a paucity of high quality randomised controlled trials, with many
      published studies focusing on establishing points of treatment, rather than
      looking for benefits of intervention over more conservative management. Despite
      this lack of good evidence views on ductus management can be entrenched, with
      accompanying loss of equipoise. This review looks at our current situation with
      regard to ductus arteriosus management and the need for good quality trials
      especially in the light of other published studies, concerning postnatal
      steroids, caffeine and oxygen which have demonstrated unexpected benefits - or
      sometimes unexpected harm - from long-familiar drugs.

PMID- 22375019
TI  - beta-Adrenergic receptor antagonists ameliorate myocyte T-tubule remodeling
      following myocardial infarction.
AB  - beta-Adrenergic receptor (AR) blockers provide substantial clinical benefits,
      including improving overall survival and left ventricular (LV) function following
      myocardial infarction (MI), though the mechanisms remain incompletely defined.
      The transverse-tubule (T-tubule) system of ventricular myocytes is an important
      determinant of cardiac excitation-contraction function. T-tubule remodeling
      occurs early during LV failure. We hypothesized that beta-AR blockers prevent T
      tubule remodeling and thereby provide therapeutic benefits. A murine model of MI
      was utilized to examine the effect of beta-AR blockers on T-tubule remodeling
      following LV MI. We applied the in situ imaging of T-tubule structure from
      Langendorff-perfused intact hearts with laser scanning confocal microscopy. We
      found that MI caused remarkable T-tubule remodeling near the infarction border
      zone and moderate LV remodeling remote from the MI. Metoprolol and carvedilol
      administered 6 d after MI for 4 wk each increased the T-tubule integrity at the
      remote and border zones. At the molecular level, both beta-AR blockers restored
      border and remote zone expression of junctophilin-2 (JP-2), which is involved in
      T-tubule organization and formation of the T-tubule/sarcoplasmic reticulum
      junctions. In contrast, beta-AR blockers had no significant effects on caveolin-3
      expression. In summary, our data show that beta-AR antagonists can protect
      against T-tubule remodeling after MI, suggesting a novel therapeutic mechanism of
      action for this drug class. Preservation of JP-2 expression may contribute to the
      beneficial effects of metoprolol and carvedilol on T-tubule remodeling.

PMID- 22375022
TI  - Hepatocyte growth factor levels of cord blood in healthy term newborns.

PMID- 22375023
TI  - Being there: a qualitative interview study with fathers present during the
      resuscitation of their baby at delivery.
AB  - OBJECTIVE: To explore fathers' experiences of the resuscitation of their baby at
      delivery. DESIGN: A descriptive, retrospective design using tape-recorded
      semistructured interviews with fathers present during the resuscitation of their
      baby at delivery. Fathers described what happened, their interactions with
      healthcare professionals, their feelings at the time and afterwards. SETTING:
      Participants were recruited from a large teaching hospital in the UK.
      PARTICIPANTS: A purposive sample of 20 fathers whose baby required resuscitation
      at delivery. RESULTS: Participant responses were analysed using thematic
      analysis. Four broad themes were identified: 'preparation', 'knowing what
      happened', 'his response' and 'impact on him'. Fathers had no difficulty
      recalling their emotions during the resuscitation. These feelings remained vivid
      and were mostly negative. Most fathers wanted to go to their baby during the
      resuscitation but did not do so. They felt they should stay with their partner,
      did not want to impede the resuscitation or felt they were not 'allowed' to go to
      their baby. The fathers' position in the room and the extent to which they were
      focusing on their partner had an impact on their recollection of what happened.
      Fathers had no opportunity to discuss the resuscitation with healthcare
      professionals afterwards. Several fathers felt they had not yet recovered from
      the experience and a few had symptoms synonymous with post-traumatic stress
      disorder. CONCLUSION: This is the first study to specifically explore fathers'
      experiences of newborn resuscitation. The findings should inform healthcare
      education, policy development and the provision of support to fathers.

PMID- 22375026
TI  - Reforming antiretroviral price negotiations and public procurement: the Mexican
      experience.
AB  - Since antiretroviral (ARV) medicines represent one of the most costly components
      of therapy for HIV in middle-income countries, ensuring their efficient
      procurement is highly relevant. In 2008, Mexico created a national commission for
      the negotiation of ARV prices to achieve price reductions for their public HIV
      treatment programmes. The objective of this study is to assess the immediate
      impact of the creation of the Mexican Commission for Price Negotiation on ARV
      prices and expenditures. A longitudinal retrospective analysis of procurement
      prices, volumes and type of the most commonly prescribed ARVs procured by the two
      largest providers of HIV/AIDS care in Mexico between 2004 and 2009 was carried
      out. These analyses were combined with 26 semi-structured key informant
      interviews to identify changes in the procurement process. Prices for ARVs
      dropped by an average of 38% after the first round of negotiations, indicating
      that the Commission was successful in price negotiations. However, when compared
      with other upper-middle-income countries, Mexico continues to pay an average of
      six times more for ARVs. The Commission's negotiations were successful in
      achieving lower ARV prices. However, price reduction in upper-middle-income
      countries suggests that the price decrease in Mexico cannot be entirely
      attributed to the Commission's first round of negotiations. In addition, key
      informants identified inefficiencies in the forecasting and procurement processes
      possibly affecting the efficiency of the negotiation process. A comprehensive
      approach to improving efficiency in the purchasing and delivery of ARVs is
      necessary, including a better clarification in the roles and responsibilities of
      the Commission, improving supply data collection and integration in forecasting
      and procurement, and the creation of a support system to monitor and provide
      feedback on patient ARV use.

PMID- 22375025
TI  - Human postmeiotic sex chromatin and its impact on sex chromosome evolution.
AB  - Sex chromosome inactivation is essential epigenetic programming in male germ
      cells. However, it remains largely unclear how epigenetic silencing of sex
      chromosomes impacts the evolution of the mammalian genome. Here we demonstrate
      that male sex chromosome inactivation is highly conserved between humans and mice
      and has an impact on the genetic evolution of human sex chromosomes. We show
      that, in humans, sex chromosome inactivation established during meiosis is
      maintained into spermatids with the silent compartment postmeiotic sex chromatin
      (PMSC). Human PMSC is illuminated with epigenetic modifications such as
      trimethylated lysine 9 of histone H3 and heterochromatin proteins CBX1 and CBX3,
      which implicate a conserved mechanism underlying the maintenance of sex
      chromosome inactivation in mammals. Furthermore, our analyses suggest that male
      sex chromosome inactivation has impacted multiple aspects of the evolutionary
      history of mammalian sex chromosomes: amplification of copy number,
      retrotranspositions, acquisition of de novo genes, and acquisition of different
      expression profiles. Most strikingly, profiles of escape genes from postmeiotic
      silencing diverge significantly between humans and mice. Escape genes exhibit
      higher rates of amino acid changes compared with non-escape genes, suggesting
      that they are beneficial for reproductive fitness and may allow mammals to cope
      with conserved postmeiotic silencing during the evolutionary past. Taken
      together, we propose that the epigenetic silencing mechanism impacts the genetic
      evolution of sex chromosomes and contributed to speciation and reproductive
      diversity in mammals.

PMID- 22375027
TI  - The pioneering spirit of Takashi Sugimura: his studies of the biochemistry of
      poly(ADP-ribosylation) and of cancer.
AB  - Takashi Sugimura has accomplished many scientific achievements in the field of
      biochemistry and in cancer research. Sugimura's group identified the novel
      polymer poly(ADP-ribose) in parallel to P. Mandel's and O. Hayaishi's groups and
      demonstrated the presence of the enzyme poly(ADP-ribose) polymerase (PARP). He
      also discovered the cognate catabolic enzyme, poly(ADP-ribose) glycohydrolase
      (PARG) and further elucidated the biology of poly(ADP-ribose). The astonishing
      discovery of pierisin, an apoptogenic peptide that ADP-ribosyaltes DNA,
      profoundly illuminates his scientific character and curiosity as well. Sugimura's
      work in cancer research shows an extraordinarily wide range, which includes the
      establishment of new methods in chemical carcinogenesis, the identification of
      various environmental mutagens/carcinogens and new tumour promoters. He also
      established the concept that cancer is a disease of DNA and contributed to the
      development of the concept of the multi-step model of carcinogenesis.

PMID- 22375028
TI  - A case of pelvic actinomycosis unrelated to an intrauterine device.

PMID- 22375029
TI  - Trends in lung cancer mortality rates in Japan, USA, UK, France and Korea based
      on the WHO mortality database.

PMID- 22375030
TI  - Plasma levels of PCSK9 and phenotypic variability in familial
      hypercholesterolemia.
AB  - The extent of hypercholesterolemia varies considerably in patients with familial
      hypercholesterolemia (FH). We hypothesized that the variability of the FH
      phenotype might be partly explained by variation in proprotein convertase
      subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of
      age who had been tested for a pathogenic LDLR or APOB mutation were eligible.
      Mutation carriers with a LDL-C level below the 75(th) percentile (called "FH
      low") were selected, as well as those with LDL-C above the 90(th) percentile
      (called "FH high"). Relatives who tested negative for the mutation were the
      "controls." PCSK9 plasma levels were assessed in 267 individuals who did not
      receive cholesterol-lowering treatment at the time of the study. Mean PCSK9
      plasma levels (95% CI) were lower in the FH-low group compared with the FH-high
      group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control
      group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically
      differ between the FH-high and control groups (P = 0.50). Plasma PCSK9 levels are
      positively associated with LDL-C levels in FH patients and might contribute to
      the phenotypic severity in this disorder. Therefore, the results of
      pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.

PMID- 22375031
TI  - Activation of GATA binding protein 6 (GATA6) sustains oncogenic lineage-survival
      in esophageal adenocarcinoma.
AB  - Gene amplification is a tumor-specific event during malignant transformation.
      Recent studies have proposed a lineage-dependency (addiction) model of human
      cancer whereby amplification of certain lineage transcription factors predisposes
      a survival mechanism in tumor cells. These tumor cells are derived from tissues
      where the lineage factors play essential developmental and maintenance roles.
      Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal
      adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a
      single gene, the embryonic endoderm transcription factor GATA6, as the selected
      target of the amplification. Overexpression of GATA6 is found in EACs that
      contain gene amplification. We find that EAC patients whose tumors carry GATA6
      amplification have a poorer survival. We show that ectopic expression of GATA6,
      together with FGFR2 isoform IIIb, increases anchorage-independent growth in
      immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of
      GATA6 significantly reduces both cell proliferation and anchorage-independent
      growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis
      pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal
      squamous cells. We show that activation of p38alpha signaling and up-regulation
      of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon
      GATA6 deprivation. We conclude that selective gene amplification of GATA6 during
      EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma.

PMID- 22375032
TI  - Disruption of ATP-binding cassette B8 in mice leads to cardiomyopathy through a
      decrease in mitochondrial iron export.
AB  - Mitochondrial iron levels are tightly regulated, as iron is essential for the
      synthesis of Fe/S clusters and heme in the mitochondria, but high levels can
      cause oxidative stress. The ATP-binding cassette (ABC) transporter ABCB8 is a
      mitochondrial inner membrane protein with an unknown function. Here, we show that
      ABCB8 is involved in mitochondrial iron export and is essential for baseline
      cardiac function. Induced genetic deletion of ABCB8 in mouse hearts resulted in
      mitochondrial iron accumulation and cardiomyopathy, as assessed by
      echocardiography and invasive hemodynamics. Mice with ABCB8 deletion in the heart
      also displayed mitochondrial damage, and higher levels of reactive oxygen species
      and cell death. Down-regulation of ABCB8 in vitro resulted in decreased iron
      export from isolated mitochondria, whereas its overexpression had the opposite
      effect. Furthermore, ABCB8 is needed for the maturation of the cytosolic Fe/S
      proteins, as its deletion in vitro and in vivo led to decreased activity of
      cytosolic, but not mitochondrial, iron-sulfur-containing enzymes. These results
      indicate that ABCB8 is essential for normal cardiac function, maintenance of
      mitochondrial iron homeostasis and maturation of cytosolic Fe/S proteins. In
      summary, this report provides characterization of a protein involved in
      mitochondrial iron export.

PMID- 22375033
TI  - Cellulose microfibril crystallinity is reduced by mutating C-terminal
      transmembrane region residues CESA1A903V and CESA3T942I of cellulose synthase.
AB  - The mechanisms underlying the biosynthesis of cellulose in plants are complex and
      still poorly understood. A central question concerns the mechanism of microfibril
      structure and how this is linked to the catalytic polymerization action of
      cellulose synthase (CESA). Furthermore, it remains unclear whether modification
      of cellulose microfibril structure can be achieved genetically, which could be
      transformative in a bio-based economy. To explore these processes in planta, we
      developed a chemical genetic toolbox of pharmacological inhibitors and
      corresponding resistance-conferring point mutations in the C-terminal
      transmembrane domain region of CESA1(A903V) and CESA3(T942I) in Arabidopsis
      thaliana. Using (13)C solid-state nuclear magnetic resonance spectroscopy and X
      ray diffraction, we show that the cellulose microfibrils displayed reduced width
      and an additional cellulose C4 peak indicative of a degree of crystallinity that
      is intermediate between the surface and interior glucans of wild type, suggesting
      a difference in glucan chain association during microfibril formation. Consistent
      with measurements of lower microfibril crystallinity, cellulose extracts from
      mutated CESA1(A903V) and CESA3(T942I) displayed greater saccharification
      efficiency than wild type. Using live-cell imaging to track fluorescently labeled
      CESA, we found that these mutants show increased CESA velocities in the plasma
      membrane, an indication of increased polymerization rate. Collectively, these
      data suggest that CESA1(A903V) and CESA3(T942I) have modified microfibril
      structure in terms of crystallinity and suggest that in plants, as in bacteria,
      crystallization biophysically limits polymerization.

PMID- 22375034
TI  - A unique series of reversibly switchable fluorescent proteins with beneficial
      properties for various applications.
AB  - Reversibly switchable fluorescent proteins (RSFPs) have attracted widespread
      interest for emerging techniques including repeated tracking of protein behavior
      and superresolution microscopy. Among the limited number of RSFPs available, only
      Dronpa is widely employed for most cell biology applications due to its monomeric
      and other favorable photochemical properties. Here we developed a series of
      monomeric green RSFPs with beneficial optical characteristics such as high photon
      output per switch, high photostability, a broad range of switching rate, and pH
      dependence, which make them potentially useful for various applications. One
      member of this series, mGeos-M, exhibits the highest photon budget and
      localization precision potential among all green RSFPs. We propose mGeos-M as a
      candidate to replace Dronpa for applications such as dynamic tracking, dual-color
      superresolution imaging, and optical lock-in detection.

PMID- 22375035
TI  - Electrical resistivity and thermal conductivity of liquid Fe alloys at high P and
      T, and heat flux in Earth's core.
AB  - Earth's magnetic field is sustained by magnetohydrodynamic convection within the
      metallic liquid core. In a thermally advecting core, the fraction of heat
      available to drive the geodynamo is reduced by heat conducted along the core
      geotherm, which depends sensitively on the thermal conductivity of liquid iron
      and its alloys with candidate light elements. The thermal conductivity for
      Earth's core is very poorly constrained, with current estimates based on a set of
      scaling relations that were not previously tested at high pressures. We perform
      first-principles electronic structure computations to determine the thermal
      conductivity and electrical resistivity for Fe, Fe-Si, and Fe-O liquid alloys.
      Computed resistivity agrees very well with existing shock compression
      measurements and shows strong dependence on light element concentration and type.
      Thermal conductivity at pressure and temperature conditions characteristic of
      Earth's core is higher than previous extrapolations. Conductive heat flux near
      the core-mantle boundary is comparable to estimates of the total heat flux from
      the core but decreases with depth, so that thermally driven flow would be
      constrained to greater depths in the absence of an inner core.

PMID- 22375036
TI  - Inadvertent prescription of gelatin-containing oral medication: its acceptability
      to patients.
AB  - When prescribing, doctors usually only consider the 'active' component of any
      drug's formulation ignoring the majority of the agents which make up the bulk of
      the tablet or capsule, collectively known as excipients. Many urological drugs
      contain the excipient gelatin which is, universally, of animal origin; this may
      conflict with the dietetic ideals of patients. A questionnaire-based study,
      undertaken between January and June 2010 in a mixed ethnicity inner-city
      population presenting with urological symptoms, asked which patients preferred
      not to ingest animal-based products, who would ask about the content of their
      prescribed treatment and who would refuse to take that medication if alternatives
      were available. Ultimately, the authors sought to find out how many patients had
      been inadvertently prescribed gelatin-containing oral medications and to suggest
      ways in which prescriptions might be more congruous with an individual patient's
      dietetic wishes. This study demonstrated that 43.2% of the study population would
      prefer not to take animal product-containing medication even if no alternative
      were available. 51% of men with lower urinary tract symptoms were also found to
      have inadvertently been prescribed gelatin-containing products against their
      preferred dietary restriction. Education of healthcare professionals about
      excipients and getting them to ask about a patient's dietetic preferences may
      help avoid inadvertent prescription of the excipient gelatin in oral medications.
      Substitution of gelatin with vegetable-based alternatives and clearer labelling
      on drug packaging are alternative strategies to help minimise the risks of
      inadvertently contravening a patient's dietetic beliefs when prescribing oral
      medication.

PMID- 22375037
TI  - Characteristics of synovial inflammation in early arthritis analysed by pixel-by
      pixel time-intensity curve shape analysis.
AB  - OBJECTIVE: Dynamic contrast-enhanced (DCE-MRI) time-intensity curve (TIC) shape
      analysis has previously been used in oncology, where fast initial enhancement and
      early washout are associated with malignancy. As RA synovium has some tumour-like
      features, we investigated DCE-MRI TIC shape expression in early arthritis in
      relationship to diagnosis. METHODS: Twenty-eight DMARD-naive, early arthritis
      patients (<1 year) with inflammation of at least one knee joint were included. At
      baseline DCE-MRI of the inflamed knee joint was performed, and the TIC shape type
      expression, maximal enhancement, maximum slope of increase and total volume of
      enhancing pixels were calculated. In addition, disease activity parameters were
      determined. At 2 years of follow-up, patients were classified as RA or non-RA
      according to established classification criteria. RESULTS: Type 4 TIC shape,
      characterized by fast initial enhancement followed by a quick washout phase, was
      significantly higher in patients fulfilling classification criteria for RA after
      2 years of follow-up compared with non-RA patients (15.6 and 7.9%, respectively,
      P = 0.02). All other DCE-MRI parameters showed no differences between the groups,
      highlighting the specificity of this observation. CONCLUSION: A high expression
      of aggressive DCE-MRI TIC shape Type 4 is associated with RA. Our results are
      consistent with the view that increased vascularity plays a key role in the
      pathogenesis of RA. This study underlines the rationale for further studies
      investigating the prospect of DCE-MRI TIC shape analysis as a diagnostic tool in
      early arthritis and the relationship with development of destructive disease.

PMID- 22375038
TI  - Indoor (222)Rn and (220)Rn concentrations and doses in Bangalore, India.
AB  - (222)Rn and (220)Rn levels have been measured using passive detector technique by
      employing time integrated solid-state nuclear track detector-based dosemeters in
      various types of houses at 10 different locations in and around Bangalore
      Metropolitan, India. The measured geometric mean concentration values of (222)Rn
      and (220)Rn levels in 200 dwellings of different types of construction were found
      to be 32.2+/-1.6 and 21.4+/-1.0 Bq m(-3), respectively. The dose rate received by
      the population of Bangalore ranged between 0.2 and 3.5 mSv y(-1) with an average
      and the geometric mean of 1.14+/-0.05 and 1.06 mSv y(-1), respectively. Overall,
      the result does not show much significant radiological risk for the inhabitants
      and the (222)Rn levels are well within the limits of global average concentration
      of 40 Bq m(-3). However, the (220)Rn levels observed were found to be higher than
      the global average of 10 Bq m(-3).

PMID- 22375039
TI  - Colloidal silver ingestion with copper and caeruloplasmin deficiency.
AB  - The copper concentration in serum can be affected by the presence of other trace
      elements such as silver. Low serum copper may result in decreased caeruloplasmin
      synthesis. We report the case of a 59-year-old woman, who was admitted to
      hospital with acute psychosis and who had been ingesting chronically, colloidal
      silver.

PMID- 22375040
TI  - Extreme hyperferritinaemia: further considerations.

PMID- 22375041
TI  - Natural history definition and a suggested clinical approach to Buerger's
      disease: a case-control study with survival analysis.
AB  - The aim of this study was first to describe the natural history of Buerger's
      disease (BD) and then to discuss a clinical approach to this disease based on
      multivariate analysis. One hundred eight patients who corresponded with
      Shionoya's criteria were selected from 2000 to 2007 for this study. Major
      amputation was considered the ultimate adverse event. Survival analyses were
      performed by Kaplan-Meier curves. Independent variables including gender,
      duration of smoking, number of cigarettes smoked per day, minor amputation events
      and type of treatments, were determined by multivariate Cox regression analysis.
      The recorded data demonstrated that BD may present in four forms, including
      relapsing-remitting (75%), secondary progressive (4.6%), primary progressive
      (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses
      within the six years after diagnosis of BD. In multivariate analysis, duration of
      smoking of more than 20 years had a significant relationship with further major
      amputation among patients with BD. Smoking cessation programs with experienced
      psychotherapists are strongly recommended for those areas in which Buerger's
      disease is common. Patients who have smoked for more than 20 years should be
      encouraged to quit smoking, but should also be recommended for more advanced
      treatment for limb salvage.

PMID- 22375042
TI  - Higher incidence of C677T polymorphism of the MTHFR gene in North Indian patients
      with vascular disease.
AB  - Homocysteine is a sulfur-containing amino acid, which is derived from dietary
      methionine. Hyperhomocysteinemia has been implicated in vascular disease for over
      a decade now, and can be treated with B vitamins. Among its causes is
      polymorphism of the MTHFR gene, the most common being the cytidine to thymidine
      at position 677 (MTHFR C677T), which gives rise to three genotypes - normal
      homozygous CC, heterozygous CT and homozygous variant TT. An attempt was made to
      ascertain the prevalence of this MTHFR C677T in our population so that preventive
      measures may accordingly be instituted. Blood samples from 70 patients with
      vascular disease and 70 healthy controls were analyzed for plasma homocysteine
      levels (chemiluminescent immunoassay) and for the presence of MTHFR C677T
      (polymerase chain reaction analysis). Homocysteine was higher in the homozygous
      subjects (TT genotype) than in the heterozygous (CT genotype). In patients, the
      frequency of the C allele was significantly lower, and that of the T allele was
      significantly higher than the corresponding frequencies in controls. In
      conclusion, the North Indian urban population has higher homocysteine levels
      associated with the TT genotype. Hence, instituting measures towards reduction of
      homocysteine levels in the population would probably reduce the incidence and
      morbidity of vascular disease in our population.

PMID- 22375043
TI  - Salvage of infected vascular graft via 'perivascular venous banding' technique
      coupled with rectus abdominis myocutaneous muscle flap transposition.
AB  - This is the case of a severe Pseudomonas aeruginosa biological vascular graft
      infection, completely involving the perianastomotic tract of a femoro - femoral
      crossover bypass and resulting in repeated bleeding from the offended vessel
      wall. After the failure of a sartorious rotational muscle flap transposition into
      the infected groin wound, this 'high-grade' vascular graft infection was finally
      treated successfully by wrapping a great saphenous vein patch reinforcement
      circumferentially around the damaged biological vascular conduit and filling the
      infected wound with a rectus abdominis myocutaneous muscle flap transposition.
      The aim of this report is to illustrate this novel, to our knowledge,
      'perivascular venous banding' technique and to evaluate the prospective of future
      testing of this surgical procedure. Starting from this singular case, we will
      also review the role of the rotational muscle flaps in the conservative
      management of major vascular graft infections.

PMID- 22375044
TI  - Aortic graft infection and mycotic aneurysm with Streptococcus equi
      zooepidemicus: two cases with favorable outcome of antibiotic treatment.
AB  - Infections with Streptococcus equi zooepidemicus are rare and are associated with
      contact with animals or animal products. There are very few reports about
      infected vascular grafts or aneurysms with this etiology. We present two
      patients. The first is a 77-year-old man with an infected bifurcated graft four
      years after an open operation for an abdominal aortic aneurysm (AAA). The second
      is a 72-year-old man with a symptomatic mycotic AAA, treated with endovascular
      aneurysm repair. Both received prolonged treatment with bactericidal antibiotics
      and responded well. Follow-up time at present is 5.5 years for the first, and 4.5
      years for the second, patient.

PMID- 22375045
TI  - Evaluation of a systematic postal screening and treatment service for genital
      Chlamydia trachomatis, with remote clinic access via the internet: a cross
      sectional study, East of England.
AB  - OBJECTIVE: England's National Chlamydia Screening Programme provides
      opportunistic testing for all 15-24-year-olds in healthcare and non-healthcare
      settings. The authors undertook an evaluation of a population service-based
      postal chlamydia screening and treatment service, with registration and access to
      the service via the internet, in order to target screening interventions more
      effectively in future. METHODS: Individuals aged between 18 and 24 years, within
      the North East Essex Primary Care Trust, were identified for chlamydia screening
      by the service between 1 December 2008 and 31 January 2009. Associations between
      test uptake and positivity, and individuals' personal characteristics, were
      examined. The efficacy of partner notification was estimated, and the costs of
      screening were compared with the national average. RESULTS: Uptake of chlamydia
      screening was 11.5%, with lower response rates among men, individuals older than
      20 years and those living in more deprived areas. The chlamydia positivity was
      4.4% and higher in those reporting multiple sexual partners, individuals older
      than 20 years and those living in more deprived areas. The proportion of partners
      notified per index case was 0.17. The service contributed to 3431 of the overall
      11,209 annual chlamydia screens of the Primary Care Trust in 2008-2009, at a cost
      of L 78 per screening test completed and L 1764 per case detected. CONCLUSIONS:
      Our evaluation shows that this service model can contribute substantially to the
      overall coverage of chlamydia screening tests. However, the costs of service
      provision per case detected and treated, using this model, were high compared to
      the National Chlamydia Screening Programme.

PMID- 22375046
TI  - Inguinal syndrome secondary to Prevotella bivia after accidental bite in
      orogenital sex.
AB  - The authors report a case of an inguinal bubo in a young man caused by an
      anaerobe, Prevotella bivia, which was acquired during oral sexual intercourse. As
      far as the authors know, this is the first reported case of a sexually
      transmitted infection by Prevotella. Prevotella spp. inhabit the oral cavity and
      are highly prevalent in bacterial vaginosis, a polymicrobial syndrome resulting
      from replacement of the normal vaginal Lactobacillus spp. flora by high
      concentrations of anaerobic microorganisms such as Prevotella spp., Mobiluncus
      spp., Gardnerella vaginalis and other uncultivated anaerobes.

PMID- 22375047
TI  - Three-dimensional docking in the MAPK p38alpha.
AB  - Mitogen-activated protein kinases (MAPKs) are central players in eukaryotic
      signaling circuitry and interact with numerous other proteins. The structure of a
      MAPK with a kinase-binding domain (KBD) from a MAPK phosphatase, MKP5, reveals
      that the contacts with the MAPK are made with the folded three-dimensional KBD,
      although the KBD occupies the same binding site on the kinase as canonical linear
      docking motifs found in substrates and MAPK kinases. This structure offers
      insights into the action of MKP5 and other MKPs.

PMID- 22375048
TI  - A distinct interaction mode revealed by the crystal structure of the kinase
      p38alpha with the MAPK binding domain of the phosphatase MKP5.
AB  - The mitogen-activated protein kinase (MAPK) cascades play a pivotal role in a
      myriad of cellular functions. The specificity and efficiency of MAPK signaling
      are controlled by docking interactions between MAPKs and their cognate proteins.
      Many MAPK-interacting partners, including substrates, MAPK kinases, phosphatases,
      and scaffolding proteins, have linear sequence motifs that mediate the
      interaction with the common docking site on MAPKs. We report the crystal
      structure of p38alpha in complex with the MAPK binding domain (KBD) from MAPK
      phosphatase 5 (MKP5) at 2.7 A resolution. In contrast to the well-known docking
      mode, the KBD binds p38alpha in a bipartite manner, in which two distinct helical
      regions of KBD engage the p38alpha docking site, which is situated on the back of
      the p38alpha active site. We also determined the crystal structure of the KBD of
      MKP7, which closely resembles the MKP5 KBD, suggesting that the mechanism of
      molecular recognition by the KBD of MKP5 is conserved in the cytoplasmic p38- and
      c-Jun N-terminal kinase-specific MKP subgroup. This previously unknown binding
      mode provides new insights into how MAPKs interact with their binding partners to
      achieve functional specificity.

PMID- 22375049
TI  - Protein O-GlcNAcylation is required for fibroblast growth factor signaling in
      Drosophila.
AB  - Glycosylation is essential for growth factor signaling through N-glycosylation of
      ligands and receptors and the biosynthesis of proteoglycans as co-receptors.
      Here, we show that protein O-GlcNAcylation is crucial for fibroblast growth
      factor (FGF) signaling in Drosophila. We found that nesthocker (nst) encodes a
      phosphoacetylglucosamine mutase and that nst mutant embryos exhibited low amounts
      of intracellular uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc), which
      disrupted protein O-GlcNAcylation. Nst was required for mitogen-activated protein
      kinase (MAPK) signaling downstream of FGF but not MAPK signaling activated by
      epidermal growth factor. nst was dispensable for the function of the FGF ligands
      and the FGF receptor's extracellular domain but was essential in the signal
      receiving cells downstream of the FGF receptor. We identified the adaptor protein
      Downstream of FGF receptor (Dof), which interacts with the FGF receptor, as the
      relevant target for O-GlcNAcylation in the FGF pathway, suggesting that protein O
      GlcNAcylation of the activated receptor complex is essential for FGF signal
      transduction.

PMID- 22375050
TI  - Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF
      kappaB, and NFAT signaling in conventional T cells.
AB  - CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of
      self-tolerance, which is crucial for the prevention of autoimmune disease, but
      T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of
      CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these
      cells to produce effector cytokines; however, the molecular mechanism of
      suppression remains unclear. Here, we showed that human T(regs) rapidly
      suppressed the release of calcium ions (Ca(2+)) from intracellular stores in
      response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+)
      signaling resulted in decreased dephosphorylation, and thus decreased activation,
      of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and
      reduced the activation of nuclear factor kappaB (NF-kappaB). In contrast, Ca(2+)
      independent events in T(cons), such as TCR-proximal signaling and activation of
      the transcription factor activator protein 1 (AP-1), were not affected during
      coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization,
      coculture with T(regs) did not block the generation of inositol 1,4,5
      trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the
      activity of NFAT and NF-kappaB and of the expression of the gene encoding the
      cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of
      intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid
      mechanism of T(reg)-mediated suppression. This increased understanding of T(reg)
      function may be exploited to generate possible therapies for the treatment of
      autoimmune diseases and cancer.

PMID- 22375051
TI  - The emerging role of linear ubiquitination in cell signaling.
AB  - The covalent attachment of ubiquitin molecules to target proteins is a
      posttranslational modification that is involved not only in signaling processes
      leading to protein degradation but also in those resulting in activation,
      proliferation, and cell death. Ubiquitination is a versatile regulation
      mechanism: In addition to single ubiquitin molecules, chains consisting of
      several ubiquitin moieties can also be attached to target proteins. The
      functional outcome of polyubiquitination depends on the lysine residue within
      ubiquitin that is used for chain elongation. The reason for this is that the
      particular linkage between two ubiquitin moieties through a specific lysine
      residue of one ubiquitin and the C terminus of the other ubiquitin creates a
      unique binding surface that is specifically recognized by specialized ubiquitin
      binding domains. New evidence indicates that besides the seven internal lysine
      residues of ubiquitin, the N terminus of ubiquitin can also be used as an
      attachment point, thereby generating linear or M1-linked polyubiquitin chains. An
      E3 complex consisting of HOIL-1, HOIP, and Sharpin specifically generates such M1
      linked ubiquitin chains in the context of various cellular signaling pathways
      that regulate cell activation and death, and it was named linear ubiquitin chain
      assembly complex (LUBAC). In this Review, we focus on the biochemistry and
      physiological role of linear ubiquitin chains generated by LUBAC. We summarize
      the function of linear ubiquitin chains in signaling pathways downstream of
      diverse cellular signaling events and provide an outlook on promising future
      directions of research.

PMID- 22375052
TI  - Focus issue: a cell's sense of direction.
AB  - The process by which cells orient their movement according to external gradients
      plays important roles in physiological and pathological processes. This Focus
      Issue of Science Signaling highlights the interplay between molecules, signaling
      pathways, and mechanisms that enable directional movement.

PMID- 22375053
TI  - How actin gets the PIP.
AB  - Actin polymerization is fundamental to many cellular activities, including
      motility, cytokinesis, and vesicle traffic. Actin dynamics must be tightly
      regulated so that cells execute a response appropriate to need, which is achieved
      through coordination of the functions of a molecular toolkit of proteins and
      phospholipids. Among the latter, phosphoinositides have a particularly important
      role, and PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) generates distinct
      phenotypic outcomes such as actin comet formation and membrane ruffling. New
      evidence reveals that it is not just the production of PI(4,5)P2 that is
      important in determining outcome, but that changes in the abundance of other
      phosphoinositides also play a role.

PMID- 22375054
TI  - Chemoattractant signaling in dictyostelium: adaptation and amplification.
AB  - The social amoebae Dictyostelium discoideum has long proved a powerful model
      organism for studying how cells sense and interpret chemoattractant gradients.
      Because of the rich behavior observed in its response to chemoattractants, as
      well as the complex nature of the signaling pathways involved, this research has
      attracted and benefited from the use of theoretical models. Recent quantitative
      experiments provide support for a popular model: the local excitation, global
      inhibition mechanism of gradient sensing. Here, I discuss these findings and
      suggest some important open problems.

PMID- 22375055
TI  - Diverse sensitivity thresholds in dynamic signaling responses by social amoebae.
AB  - The complex transition from a single-cell to a multicellular life form during the
      formation of a fruiting body by the amoeba Dictyostelium discoideum is
      accompanied by a pulsatile collective signaling process that instigates
      chemotaxis of the constituent cells. Although the cells used for the analysis of
      this phenomenon are normally genetically identical (isogenic), it is not clear
      whether they are equally responsive to the waves of the signaling stimulus, nor
      is it clear how responses across the population influence collective cell
      behavior. Here, we found that isogenic Dictyostelium cells displayed differing
      sensitivities to the chemoattractant cyclic adenosine monophosphate (cAMP).
      Furthermore, the resulting signaling responses could be explained by a model in
      which cells are refractory to further stimulation for 5 to 6 min after the
      initial input and the signaling output is amplified, with the amplification
      threshold varying across the cells in the population. This pathway structure
      could explain intracellular amplification of the chemoattractant gradient during
      cell migration. The new model predicts that diverse cell responsiveness can
      facilitate collective cell behavior, specifically due to the presence of a small
      number of cells in the population with increased responsiveness that aid in
      propagating the initial cAMP signaling wave across the cell population.

PMID- 22375057
TI  - Facial rejuvenation surgery: a retrospective study of 8788 cases.
AB  - BACKGROUND: Surgical rejuvenation of the aging face is common in aesthetic
      surgery, and many surgical techniques have been described for accomplishing it.
      The keys to consistent results are the surgeon's judgment and ability to
      individualize a treatment plan according to the patient's needs. To obtain
      natural-appearing results, the surgeon must consider the morphological
      characteristics of the aging face. OBJECTIVES: The authors describe their
      approach for "round" facelift technique and strategies for avoiding
      complications. METHODS: This retrospective study included 8788 consecutive
      patients who underwent facelift procedures in a single clinic between 1958 and
      2010. All cases involved the round-lifting technique. RESULTS: Patients in this
      series ranged in age from 28 to 84 years. The percentage of male patients
      increased in later years (6.3% in 1970-1974 vs 18.6% in 1986-2010), and there was
      a trend toward increasing age after 1979 (17.7% of patients aged 60 years or
      older vs 8.3% before 1980). Submental liposuction was the most common facelift
      procedure performed (92.2% of patients, 1990-2010). Up to 97% of the cases
      treated after 1999 underwent repositioning of the malar fat pad. The overall
      complication rate was 4.5%, with the most frequent complications being hematoma
      (3%) and cutaneous slough or necrosis (1%). CONCLUSIONS: Repositioning the vector
      connecting the tragus with the Darwin tubercle provides more natural correction
      of aging tissues than do other techniques. The authors' intent was to keep the
      structures in their natural location, as they had been prior to aging.
      Superficial musculo-aponeurotic system (SMAS) plication, malar fat pad
      repositioning, and correct traction of facial tissues showed satisfactory
      results. This technique is less aggressive than undermining of the SMAS and deep
      plane techniques. LEVEL OF EVIDENCE: 4.

PMID- 22375056
TI  - PTEN protein phosphatase activity correlates with control of gene expression and
      invasion, a tumor-suppressing phenotype, but not with AKT activity.
AB  - The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10
      (PTEN) has a well-characterized lipid phosphatase activity and a poorly
      characterized protein phosphatase activity. We show that both activities are
      required for PTEN to inhibit cellular invasion and to mediate most of its largest
      effects on gene expression. PTEN appears to dephosphorylate itself at threonine
      366, and mutation of this site makes lipid phosphatase activity sufficient for
      PTEN to inhibit invasion. We propose that the dominant role for PTEN's protein
      phosphatase activity is autodephosphorylation-mediated regulation of its lipid
      phosphatase activity. Because PTEN's regulation of invasion and these changes in
      gene expression required lipid phosphatase activity, but did not correlate with
      the total cellular abundance of its phosphatidylinositol 3,4,5-trisphosphate
      (PIP3) lipid substrate or AKT activity, we propose that localized PIP3 signaling
      may play a role in those PTEN-mediated processes that depend on both its protein
      and lipid phosphatase activities. Finally, we identified a tumor-derived PTEN
      mutant selectively lacking protein phosphatase activity, indicating that in some
      circumstances the regulation of invasion and not that of AKT can correlate with
      PTEN-mediated tumor suppression.

PMID- 22375058
TI  - Use of registries to complement clinical trials in renal artery stenting.

PMID- 22375060
TI  - Rab27a-mediated protease release regulates neutrophil recruitment by allowing
      uropod detachment.
AB  - Neutrophil migration is vital for immunity and precedes effector functions such
      as pathogen killing. Here, we report that this process is regulated by the Rab27a
      GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a
      KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell
      microscopy suggests that delayed uropod detachment causes the migratory defect.
      Surface expression of CD11b, a key adhesion molecule, is increased in chemokine
      stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover
      delay caused by a defect in elastase secretion from azurophilic granules at the
      rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that
      Rab27a-dependent protease secretion regulates neutrophil migration through
      proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved
      in cell migration and invasion.

PMID- 22375059
TI  - Different effects of Sec61alpha, Sec62 and Sec63 depletion on transport of
      polypeptides into the endoplasmic reticulum of mammalian cells.
AB  - Co-translational transport of polypeptides into the endoplasmic reticulum (ER)
      involves the Sec61 channel and additional components such as the ER lumenal Hsp70
      BiP and its membrane-resident co-chaperone Sec63p in yeast. We investigated
      whether silencing the SEC61A1 gene in human cells affects co- and post
      translational transport of presecretory proteins into the ER and post
      translational membrane integration of tail-anchored proteins. Although silencing
      the SEC61A1 gene in HeLa cells inhibited co- and post-translational transport of
      signal-peptide-containing precursor proteins into the ER of semi-permeabilized
      cells, silencing the SEC61A1 gene did not affect transport of various types of
      tail-anchored protein. Furthermore, we demonstrated, with a similar knockdown
      approach, a precursor-specific involvement of mammalian Sec63 in the initial
      phase of co-translational protein transport into the ER. By contrast, silencing
      the SEC62 gene inhibited only post-translational transport of a signal-peptide
      containing precursor protein.

PMID- 22375061
TI  - The IplA Ca2+ channel of Dictyostelium discoideum is necessary for chemotaxis
      mediated through Ca2+, but not through cAMP, and has a fundamental role in
      natural aggregation.
AB  - During aggregation of Dictyostelium discoideum, nondissipating, symmetrical,
      outwardly moving waves of cAMP direct cells towards aggregation centers. It has
      been assumed that the spatial and temporal characteristics of the front and back
      of each cAMP wave regulate both chemokinesis and chemotaxis. However, during the
      period preceding aggregation, cells acquire not only the capacity to chemotax in
      a spatial gradient of cAMP, but also in a spatial gradient of Ca(2+). The null
      mutant of the putative IplA Ca(2+) channel gene, iplA(-), undergoes normal
      chemotaxis in spatial gradients of cAMP and normal chemokinetic responses to
      increasing temporal gradients of cAMP, both generated in vitro. However, iplA(-)
      cells lose the capacity to undergo chemotaxis in response to a spatial gradient
      of Ca(2+), suggesting that IplA is either the Ca(2+) chemotaxis receptor or an
      essential component of the Ca(2+) chemotaxis regulatory pathway. In response to
      natural chemotactic waves generated by wild-type cells, the chemokinetic response
      of iplA(-) cells to the temporal dynamics of the cAMP wave is intact, but the
      capacity to reorient in the direction of the aggregation center at the onset of
      each wave is lost. These results suggest that transient Ca(2+) gradients formed
      between cells at the onset of each natural cAMP wave augment reorientation
      towards the aggregation center. If this hypothesis proves correct, it will
      provide a more complex contextual framework for interpreting D. discoideum
      chemotaxis.

PMID- 22375063
TI  - Deletion of K1/K10 does not impair epidermal stratification but affects
      desmosomal structure and nuclear integrity.
AB  - Keratins K1 and K10 are the most abundant proteins in the upper epidermis where
      they polymerize to form intermediate filaments (IFs). In addition to their well
      established function in providing epidermal stability, K1/K10 (i.e. the dimer
      between K1 and K10) IFs are supposed to be important for terminal epidermal
      differentiation and barrier formation. It was previously shown that the
      imbalanced deletion of one of the partner keratins, K10, disturbed epidermal
      homoeostasis, although stability was provided by compensatory upregulation of
      K5/K14, which formed IFs together with the remaining K1. Here, we show that
      deletion of both partner keratins, K1 and K10, results in lethal postnatal skin
      fragility in mice. Krt1(-/-);Krt10(-/-) mice revealed that K1/K10 IFs are
      unexpectedly dispensable for epidermal stratification. Although the stratum
      corneum was less compact and cornified envelope differentiation was impaired, a
      dye exclusion assay showed that the development of a functional water barrier was
      surprisingly independent from the presence of K1/K10 IFs. The deletion of K1/K10
      was not compensated by any other keratin pair such as the basal epidermal
      keratins K5/K14, and electron microscopy revealed total absence of IFs in the
      suprabasal epidermis. Although plakoglobin was unchanged, the expression of the
      desmosomal proteins desmoplakin, desmocollin 1 and desmoglein 1 were altered and
      suprabasal desmosomes were smaller in Krt1(-/-);Krt10(-/-) than in wild-type
      epidermis suggesting an involvement of K1/K10 IFs in desmosome dynamics.
      Furthermore, Krt1(-/-);Krt10(-/-) mice showed premature loss of nuclei during
      epidermal differentiation and lower levels of emerin, lamin A/C and Sun1,
      revealing a previously unknown function for IFs in maintaining nuclear integrity
      in the upper epidermis.

PMID- 22375062
TI  - Plo1 phosphorylates Dam1 to promote chromosome bi-orientation in fission yeast.
AB  - The fungal-specific heterodecameric outer kinetochore DASH complex facilitates
      the interaction of kinetochores with spindle microtubules. In budding yeast,
      where kinetochores bind a single microtubule, the DASH complex is essential, and
      phosphorylation of Dam1 by the Aurora kinase homologue, Ipl1, causes detachment
      of kinetochores from spindle microtubules. We demonstrate that in the distantly
      related fission yeast, where the DASH complex is not essential for viability and
      kinetochores bind multiple microtubules, Dam1 is instead phosphorylated on serine
      143 by the Polo kinase homologue, Plo1, during prometaphase and metaphase. This
      phosphorylation site is conserved in most fungal Dam1 proteins, including budding
      yeast Dam1. We show that Dam1 phosphorylation by Plo1 is dispensable for DASH
      assembly and chromosome retrieval but instead aids tension-dependent chromosome
      bi-orientation.

PMID- 22375064
TI  - SUMO conjugation is required for the assembly of Drosophila Su(Hw) and Mod(mdg4)
      into insulator bodies that facilitate insulator complex formation.
AB  - Chromatin insulators are special regulatory elements involved in modulation of
      enhancer-promoter interactions. The best studied insulators in Drosophila require
      Suppressor of Hairy Wing [Su(Hw)], Modifier of mdg4 [Mod(mdg4)] and centrosomal
      190 kDa (CP190) proteins to be functional. These insulator proteins are
      colocalized in nuclear speckles named insulator bodies. Here, we demonstrate that
      post-translational modification of insulator proteins by small ubiquitin-like
      modifier (SUMO) and intact CP190 protein is crucial for insulator body formation.
      Inactivation of SUMO binding sites in Mod(mdg4)-67.2 leads to the inability of
      the mutant protein and Su(Hw) to be assembled into insulator bodies. In vivo
      functional tests show that a smaller amount of intact Mod(mdg4)-67.2, compared
      with the mutant protein, is required to restore the normal activity of the Su(Hw)
      insulator. However, high expression of mutant Mod(mdg4)-67.2 completely rescues
      the insulator activity, indicating that sumoylation is not necessary for enhancer
      blocking. These results suggest that insulator bodies function as a depot of
      sumoylated proteins that are involved in insulation and can facilitate insulator
      complex formation, but are nonessential for insulator action.

PMID- 22375066
TI  - AMPK phosphorylation by Ssp1 is required for proper sexual differentiation in
      fission yeast.
AB  - The AMP-activated protein kinase (AMPK) is a central regulator of cellular energy
      homeostasis, which, in response to a fall in intracellular ATP levels, activates
      energy-producing pathways and inhibits energy-consuming processes. Here, we
      report that fission yeast cells lacking AMPK activity are unable to advance entry
      into mitosis in response to nitrogen starvation and cannot undergo proper G1
      arrest and cell differentiation. We also show that AMPK is important in the
      promotion of the nuclear localization and accumulation of the Ste11 transcription
      factor. As in animal cells, the fission yeast CaMKK ortholog (Ssp1)
      phosphorylates and activates the catalytic subunit of AMPK (Ssp2) in its
      activation loop (Thr189) when cells are starved for nitrogen or glucose.
      Interestingly, we found that the phosphorylation of Ssp2 on Thr189 is required
      for nuclear accumulation of AMPK. Our data demonstrate the existence of a signal
      transduction pathway activated by nutrient starvation that triggers Ssp2
      phosphorylation and AMPK redistribution from the cytoplasm to the nucleus. This
      pathway is important to advance fission cells into mitosis and to establish a
      timely pre-Start G1 cell cycle arrest for mating.

PMID- 22375065
TI  - Multiple post-translational modifications regulate E-cadherin transport during
      apoptosis.
AB  - E-cadherin is synthesized as a precursor and then undergoes cleavage by
      proprotein convertases. This processing is essential for E-cadherin maturation
      and cell adhesion. Loss of cell adhesion causes detachment-induced apoptosis,
      which is called anoikis. Anoikis can be inhibited despite loss of cell-matrix
      interactions by preserving E-cadherin-mediated cell-cell adhesion. Conversely,
      acute loss of E-cadherin sensitizes cells to apoptosis by unknown post
      translational mechanisms. After treatment of breast cancer cells with drugs, we
      found that two independent modifications of E-cadherin inhibit its cell surface
      transport. First, O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of
      the cytoplasmic domain retains E-cadherin in the endoplasmic reticulum. Second,
      incomplete processing by proprotein convertases arrests E-cadherin transport late
      in the secretory pathway. We demonstrated these E-cadherin modifications
      (detected by specific lectins and antibodies) do not affect binding to alpha
      catenin, beta-catenin or gamma-catenin. However, binding of E-cadherin to Type I
      gamma phosphatidylinositol phosphate kinase (PIPKIgamma), a protein required for
      recruitment of E-cadherin to adhesion sites, was blocked by O-GlcNAc
      glycosylation (O-GlcNAcylation). Consequently, E-cadherin trafficking to the
      plasma membrane was inhibited. However, deletion mutants that cannot be O
      GlcNAcylated continued to bind PIPKIgamma, trafficked to the cell surface and
      delayed apoptosis, confirming the biological significance of the modifications
      and PIPKIgamma binding. Thus, O-GlyNAcylation of E-cadherin accelerates
      apoptosis. Furthermore, cell-stress-induced inactivation of proprotein
      convertases, inhibited E-cadherin maturation, further exacerbating apoptosis. The
      modifications of E-cadherin by O-GlcNAcylation and lack of pro-region processing
      represent novel mechanisms for rapid regulation of cell surface transport of E
      cadherin in response to intoxication.

PMID- 22375067
TI  - Has electroconvulsive therapy use remained stable over time? A decade of
      electroconvulsive therapy service provision in Victoria, Australia.
AB  - OBJECTIVE: Despite the long history of electroconvulsive therapy (ECT) as a
      psychiatric treatment modality in Australia, existing literature regarding ECT
      use and practices in Australia is limited. In this unique study, we report ECT
      provision in Victoria to adults aged 25 years and over from 1998 to 2007, based
      on complete data from all public and private treatment settings within the State;
      compare our results to previous literature in the field; and offer possible
      explanations for these findings as a basis for future research. METHOD: Analysis
      of statutory ECT service provision data collected by the Office of the Chief
      Psychiatrist of Victoria. RESULTS: ECT use declined overall from 2001 onward,
      followed by a small increase in use in 2007. Eighty per cent of patients received
      ECT for depression and 14% for psychosis. Sixty-two per cent of ECT recipients
      were women. Although patients aged 65 years and over were small in number, age
      adjustment of data was indicative of a higher utilisation rate in this group.
      With increasing age, the percentage of ECT recipients treated for depression
      increased, whereas the percentage treated for psychosis decreased. Sixty per cent
      of patients were treated in the public sector. Public-private sector ECT use did
      not differ greatly for depression, but more patients were treated in the public
      sector for psychosis. The majority of patients with depression received treatment
      voluntarily, but the converse was true for patients with psychosis. Unilateral
      electrode placement predominated. CONCLUSIONS: While utilisation rates gradually
      declined over the decade studied, patients continued receiving ECT in significant
      numbers, suggesting its role in treating severe mental illness is far from
      superceded. The present, population-level research cannot explain the causative
      factors underlying the patterns observed, but raises interesting questions for
      further investigation. Ongoing collection of statutory ECT data in a manner
      making it amenable to research applications is recommended.

PMID- 22375068
TI  - The optimal viewing position in face recognition.
AB  - In English word recognition, the best recognition performance is usually obtained
      when the initial fixation is directed to the left of the center (optimal viewing
      position, OVP). This effect has been argued to involve an interplay of left
      hemisphere lateralization for language processing and the perceptual experience
      of fixating at word beginnings most often. While both factors predict a left
      biased OVP in visual word recognition, in face recognition they predict
      contrasting biases: People prefer to fixate the left half-face, suggesting that
      the OVP should be to the left of the center; nevertheless, the right hemisphere
      lateralization in face processing suggests that the OVP should be to the right of
      the center in order to project most of the face to the right hemisphere. Here, we
      show that the OVP in face recognition was to the left of the center, suggesting
      greater influence from the perceptual experience than hemispheric asymmetry in
      central vision. In contrast, hemispheric lateralization effects emerged when
      faces were presented away from the center; there was an interaction between
      presented visual field and location (center vs. periphery), suggesting
      differential influence from perceptual experience and hemispheric asymmetry in
      central and peripheral vision.

PMID- 22375069
TI  - Immunophyllin ligands show differential effects on alcohol self-administration in
      C57BL mice.
AB  - High abstinence rates characterize alcohol-dependent liver graft recipients. The
      immunosuppressants cyclosporine A (CsA) and tacrolimus (TRL) also inhibit
      calcineurin (CLN) in the brain. Previously, we found that CsA reduces alcohol
      consumption in C57BL/6J mice. The goals of the present study were: 1) to compare
      the ethanol preference effects of CsA against TRL, as well as sirolimus (SRL), an
      immunosuppressant without CLN inhibition and 2) to establish that reduction of
      alcohol consumption is not caused by caloric reinforcement from these ligands.
      C57BL/6J mice trained to imbibe ethanol consumed ethanol or sucrose in a modified
      limited-access drinking-in-the-dark paradigm; test groups received vehicle or
      doses of CsA (5-50 mg/kg), TRL (0.5-2.5 mg/kg), or SRL (1.0-5.0 mg/kg) for 5
      consecutive days, 30 min before each 2-h limited-access session. Brain CsA, TRL,
      and SRL concentrations were measured. CsA (p < 0.001) and TRL (p < 0.01) each
      decreased ethanol consumption, whereas SRL showed no significant effects at any
      dose. Effective doses included CsA at 10 mg/kg and above and TRL at 2.5 mg/kg.
      CsA (50 mg/kg) did not reduce sucrose consumption. Both CsA and TRL reached
      significant brain concentrations compared with very low values of SRL. These data
      suggest that CsA and TRL may reduce alcohol preference through central CLN
      inhibition rather than by immunosuppression.

PMID- 22375070
TI  - Smoking and socioeconomic status in England: the rise of the never smoker and the
      disadvantaged smoker.
AB  - BACKGROUND: Since 2000 various tobacco control measures have been implemented in
      the UK. Changes in the smoking status of low and high socioeconomic status (SES)
      groups in England during this period (2001-08) are explored. METHODS: Secondary
      analysis of the Health Survey for England general population samples was
      undertaken. Over 88 000 adults, age 16 or over, living in England were included.
      Smoking status (current, ex or never) was reported. SES was assessed through a
      count of seven possible indicators of disadvantage: National Statistics Socio
      Economic Classification (NSSEC), neighbourhood index of multiple deprivation,
      lone parenting, car availability, housing tenure, income and unemployment.
      RESULTS: Smoking rates were four times higher among the most disadvantaged [60.7%
      (95% CI: 58.2-63.3)] than the most affluent [15.3% (95% CI: 14.8-15.8)]. Smoking
      prevalence declined between 2001 and 2008 except among the multiply
      disadvantaged. This trend appeared to be due to an increase in never smoking
      rather than an increase in quitting. Disadvantage declined among non-smokers but
      not smokers. CONCLUSIONS: In general never smoking and affluence increased in
      England over this period. The disadvantaged, however, did not experience the
      decline in smoking and smokers missed out from the increase in affluence. Smoking
      and disadvantage may increasingly coexist.

PMID- 22375071
TI  - Identification of a highly transmissible animal-independent Staphylococcus aureus
      ST398 clone with distinct genomic and cell adhesion properties.
AB  - A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has
      emerged as a major cause of acute infections in individuals who have close
      contact with livestock. More recently, the emergence of an animal-independent
      ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several
      countries. However, the limited surveillance of MSSA has precluded an accurate
      assessment of the global spread of ST398 and its clinical relevance. Here we
      provide evidence that ST398 is a frequent source of MSSA infections in northern
      Manhattan and is readily transmitted between individuals in households. This
      contrasts with the limited transmissibility of livestock-associated ST398 (LA
      ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed
      that the chromosome of the human-associated ST398 MSSA clone is smaller than that
      of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic
      elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage
      phi3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While
      most of the core genome was conserved between the human ST398 MSSA clone and
      S0385, these strains differed substantially in their repertoire and composition
      of intact adhesion genes. These genetic changes were associated with
      significantly enhanced adhesion of human ST398 MSSA isolates to human skin
      keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread
      independent of animal contact using an optimized repertoire of MGEs and adhesion
      molecules adapted to transmission among humans. IMPORTANCE: Staphylococcus aureus
      strains have generally been considered to be species specific. However, cross
      species transfers of S. aureus clones, such as ST398 methicillin-resistant S.
      aureus (MRSA), from swine to humans have been reported. Recently, we observed the
      emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing
      strain of humans in northern Manhattan. Here we report that ST398 is a frequent
      cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily
      transmitted within households, independent of animal contact. We discovered that
      human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due
      to fewer mobile genetic elements. Human and LA-ST398 strains also differed in
      their composition of adhesion genes and their ability to bind to human skin
      keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our
      findings illustrate the importance of implementing molecular surveillance of MSSA
      given the evidence for the rapid and clinically undetected spread of ST398 MSSA.

PMID- 22375072
TI  - Genetic reporter system for positioning of proteins at the bacterial pole.
AB  - Spatial organization within bacteria is fundamental to many cellular processes,
      although the basic mechanisms underlying localization of proteins to specific
      sites within bacteria are poorly understood. The study of protein positioning has
      been limited by a paucity of methods that allow rapid large-scale screening for
      mutants in which protein positioning is altered. We developed a genetic reporter
      system for protein localization to the pole within the bacterial cytoplasm that
      allows saturation screening for mutants in Escherichia coli in which protein
      localization is altered. Utilizing this system, we identify proteins required for
      proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely
      distributed bacterial virulence proteins, are secreted at the bacterial pole. We
      show that the conserved cell division protein FtsQ is required for localization
      of IcsA and other autotransporters to the pole. We demonstrate further that this
      system can be applied to the study of proteins other than autotransporters that
      display polar positioning within bacterial cells. IMPORTANCE: Many proteins
      localize to specific sites within bacterial cells, and localization to these
      sites is frequently critical to proper protein function. The mechanisms that
      underlie protein localization are incompletely understood, in part because of the
      paucity of methods that allow saturation screening for mutants in which protein
      localization is altered. We developed a genetic reporter assay that enables
      screening of bacterial populations for changes in localization of proteins to the
      bacterial pole, and we demonstrate the utility of the system in identifying
      factors required for proper localization of the polar Shigella autotransporter
      protein IcsA. Using this method, we identify the conserved cell division protein
      FtsQ as being required for positioning of IcsA to the bacterial pole. We
      demonstrate further that the requirement for FtsQ for polar positioning applies
      to other autotransporters and that the method can be applied to polar proteins
      other than autotransporters.

PMID- 22375073
TI  - A unique chromosomal rearrangement in the Cryptococcus neoformans var. grubii
      type strain enhances key phenotypes associated with virulence.
AB  - The accumulation of genomic structural variation between closely related
      populations over time can lead to reproductive isolation and speciation. The
      fungal pathogen Cryptococcus is thought to have recently diversified, forming a
      species complex containing members with distinct morphologies, distributions, and
      pathologies of infection. We have investigated structural changes in genomic
      architecture such as inversions and translocations that distinguish the most
      pathogenic variety, Cryptococcus neoformans var. grubii, from the less clinically
      prevalent Cryptococcus neoformans var. neoformans and Cryptococcus gattii.
      Synteny analysis between the genomes of the three Cryptococcus species/varieties
      (strains H99, JEC21, and R265) reveals that C. neoformans var. grubii possesses
      surprisingly few unique genomic rearrangements. All but one are relatively small
      and are shared by all molecular subtypes of C. neoformans var. grubii. In
      contrast, the large translocation peculiar to the C. neoformans var. grubii type
      strain is found in all tested subcultures from multiple laboratories, suggesting
      that it has possessed this rearrangement since its isolation from a human
      clinical sample. Furthermore, we find that the translocation directly disrupts
      two genes. The first of these encodes a novel protein involved in metabolism of
      glucose at human body temperature and affects intracellular levels of trehalose.
      The second encodes a homeodomain-containing transcription factor that modulates
      melanin production. Both mutations would be predicted to increase pathogenicity;
      however, when recreated in an alternate genetic background, these mutations do
      not affect virulence in animal models. The type strain of C. neoformans var.
      grubii in which the majority of molecular studies have been performed is
      therefore atypical for carbon metabolism and key virulence attributes.
      IMPORTANCE: The fungal pathogen Cryptococcus is a major cause of mortality among
      the immunocompromised population, primarily in AIDS patients of sub-Saharan
      Africa. Most research into the particular variety of Cryptococcus responsible for
      the vast majority of infections, Cryptococcus neoformans var. grubii, is
      performed using the type strain isolated in 1978 from a Hodgkin's disease patient
      from North Carolina. We have determined that this particular isolate contains a
      chromosomal translocation that directly interrupts two genes, which all
      descendants of this strain from various research laboratories appear to possess.
      Disruption of these two genes affects multiple virulence factors of Cryptococcus,
      particularly the ability to grow at human body temperature, which could have wide
      ranging implications for molecular genetic studies and virulence assays using
      this important strain.

PMID- 22375074
TI  - The mzIdentML data standard for mass spectrometry-based proteomics results.
AB  - We report the release of mzIdentML, an exchange standard for peptide and protein
      identification data, designed by the Proteomics Standards Initiative. The format
      was developed by the Proteomics Standards Initiative in collaboration with
      instrument and software vendors, and the developers of the major open-source
      projects in proteomics. Software implementations have been developed to enable
      conversion from most popular proprietary and open-source formats, and mzIdentML
      will soon be supported by the major public repositories. These developments
      enable proteomics scientists to start working with the standard for exchanging
      and publishing data sets in support of publications and they provide a stable
      platform for bioinformatics groups and commercial software vendors to work with a
      single file format for identification data.

PMID- 22375075
TI  - Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects
      beta-oxidation activity.
AB  - It is known that estrogen receptors can function as nuclear receptors and
      transcription factors in the nucleus and as signaling molecules in the plasma
      membrane. In addition, the localization of the receptors in mitochondria suggests
      that they may play important roles in mitochondria. In order to identify novel
      proteins that are involved in ERalpha-mediated actions of estrogens, we used a
      proteomic method that integrated affinity purification, two-dimensional gel
      electrophoresis, and mass spectrometry to isolate and identify cellular proteins
      that interact with ERalpha. One of the proteins identified was trifunctional
      protein beta-subunit (HADHB), a mitochondrial protein that is required for beta
      oxidation of fatty acids in mitochondria. We have verified the interaction
      between ERalpha and HADHB by coimmunoprecipitation and established that ERalpha
      directly binds to HADHB by performing an in vitro binding assay. In addition, we
      have shown that ERalpha colocalizes with HADHB in the mitochondria by confocal
      microscopy, and the two proteins interact with each other within mitochondria by
      performing coimmunoprecipitation using purified mitochondria as starting
      materials. We have demonstrated that the expression of ERalpha affects HADHB
      activity, and a combination of 17beta-estrodiol and tamoxifen affects the
      activity of HADHB prepared from human breast cancer cells that express ERalpha
      but not from the cells that are ERalpha deficient. Furthermore, we have
      demonstrated that 17beta-estrodiol plus tamoxifen affects the association of
      ERalpha with HADHB in human cell extract. Our results suggest that HADHB is a
      functional molecular target of ERalpha in the mitochondria, and the interaction
      may play an important role in the estrogen-mediated lipid metabolism in animals
      and humans.

PMID- 22375076
TI  - Broad-spectrum four-dimensional orthogonal electrophoresis: a novel
      comprehensively feasible system for protein complexomics investigation.
AB  - The major challenge of "protein complexomics" is to separate intact protein
      complexes or interactional proteins without dissociation or denaturation from
      complex biological samples and to characterize structural subunits of protein
      complexes. To address these issues, we developed a novel approach termed "broad
      spectrum four-dimensional orthogonal electrophoresis (BS4-DE) system," which is
      composed of a nondenaturing part I and denaturing part II. Here we developed a
      mild acidic-native-PAGE to constitute part I, together with native-thin-layer-IEF
      and basic-native-PAGE, widening the range of BS4-DE system application for
      extremely basic proteins with the range of pI from about 8 to 11 (there are
      obviously 1000 kinds of proteins in this interval), and also speculated on the
      mechanism of separating. We first proposed ammonium hydroxide-ultrasonic protein
      extractive strategy as a seamless connection between part I and part II, and also
      speculated on the extractive mechanism. More than 4000 protein complexes could be
      theoretically solved by this system. Using this approach, we focus on blood rich
      in protein complexes which make it challenging to sera/plasma proteome study. Our
      results indicated that the BS4-DE system could be applied to blood protein
      complexomics investigation, providing a comprehensively feasible approach for
      disease proteomics.

PMID- 22375077
TI  - How family caregivers' medical and moral assumptions influence decision making
      for patients in the vegetative state: a qualitative interview study.
AB  - BACKGROUND: Decisions on limiting life-sustaining treatment for patients in the
      vegetative state (VS) are emotionally and morally challenging. In Germany,
      doctors have to discuss, together with the legal surrogate (often a family
      member), whether the proposed treatment is in accordance with the patient's will.
      However, it is unknown whether family members of the patient in the VS actually
      base their decisions on the patient's wishes. OBJECTIVE: To examine the role of
      advance directives, orally expressed wishes, or the presumed will of patients in
      a VS for family caregivers' decisions on life-sustaining treatment. METHODS AND
      SAMPLE: A qualitative interview study with 14 next of kin of patients in a VS in
      a long-term care setting was conducted; 13 participants were the patient's legal
      surrogates. Interviews were analysed according to qualitative content analysis.
      RESULTS: The majority of family caregivers said that they were aware of
      aforementioned wishes of the patient that could be applied to the VS condition,
      but did not base their decisions primarily on these wishes. They gave three
      reasons for this: (a) the expectation of clinical improvement, (b) the
      caregivers' definition of life-sustaining treatments and (c) the moral obligation
      not to harm the patient. If the patient's wishes were not known or not revealed,
      the caregivers interpreted a will to live into the patient's survival and non
      verbal behaviour. CONCLUSIONS: Whether or not prior treatment wishes of patients
      in a VS are respected depends on their applicability, and also on the medical
      assumptions and moral attitudes of the surrogates. We recommend repeated
      communication, support for the caregivers and advance care planning.

PMID- 22375078
TI  - Terminating clinical trials without sufficient subjects.
AB  - Medical research involving human subjects can be risky and burdensome. Therefore,
      such research must be reviewed and approved by a Research Ethics Committee (REC).
      To guarantee the safety of the subjects, it is very important that these studies
      be conducted in accordance with the approved protocol. An important issue in this
      respect is whether studies include the requisite number of subjects based on the
      research question. The research question is unlikely to be answered reliably if
      the requisite number of subjects is not met. In such cases, subjects are exposed
      to unnecessary risks and burdens. In this descriptive study, the authors
      evaluated how frequently studies are completed with the required number of
      subjects. Moreover, the authors identified the characteristics of research that
      does and does not include the required number of subjects. The results of this
      study show that a considerable proportion of studies (41/107) were terminated
      although they failed to recruit a sufficient number of subjects. Furthermore, the
      authors found that investigator-initiated studies have significantly (p=0.028)
      more problems in recruiting the requisite number of subjects than studies
      initiated by pharmaceutical companies. Potential solutions are discussed to
      reduce the number of studies that do not include a sufficient number of subjects.

PMID- 22375079
TI  - Fatal fetal paternalism.
AB  - Heuser and colleagues' survey of obstetricians provides a valuable insight into
      the current management of severe fetal anomalies in the United States. Their
      survey reveals two striking features - that counselling for these anomalies is
      far from neutral, and that there is significant variability between clinicians in
      their approach to management. In this commentary I outline the reasons to be
      concerned about both of these. Directiveness in counselling arguably represents a
      form of paternalism, and the evident variability in practice is likely the result
      of physician personal values. However, Heuser's survey may, by shining a light on
      practice, provide an important step towards a more consistent approach.

PMID- 22375080
TI  - Mahatma Gandhi's view on euthanasia and assisted suicide.
AB  - To many in India and elsewhere, the life and thoughts of Mohandas Karamchand
      Gandhi are a source of inspiration. The idea of non-violence was pivotal in his
      thinking. In this context, Gandhi reflected upon the possibility of what is now
      called 'euthanasia' and 'assisted suicide'. So far, his views on these practices
      have not been properly studied. In his reflections on euthanasia and assisted
      suicide, Gandhi shows himself to be a contextually flexible thinker. In spite of
      being a staunch defender of non-violence, Gandhi was aware that violence may
      sometimes be unavoidable. Under certain conditions, killing a living being could
      even be an expression of non-violence. He argued that in a few rare cases it may
      be better to kill people who are suffering unbearably at the end of life. In this
      way, he seems to support euthanasia and assisted suicide. Yet, Gandhi also
      thought that as long as care can be extended to a dying patient, his or her
      suffering could be relieved. Since in most cases relief was thus possible,
      euthanasia and assisted suicide were in fact redundant. By stressing the
      importance of care and nursing as an alternative to euthanasia and assisted
      suicide, Gandhi unconsciously made himself an early advocate of palliative care
      in India. This observation could be used to strengthen and promote the further
      development of palliative care in India.

PMID- 22375081
TI  - How to depolarise the ethical debate over human embryonic stem cell research (and
      other ethical debates too!).
AB  - The contention of this paper is that the current ethical debate over embryonic
      stem cell research is polarised to an extent that is not warranted by the
      underlying ethical conflict. It is argued that the ethical debate can be rendered
      more nuanced, and less polarised, by introducing non-binary notions of moral
      rightness and wrongness. According to the view proposed, embryonic stem cell
      research--and possibly other controversial activities too--can be considered 'a
      little bit right and a little bit wrong'. If this idea were to become widely
      accepted, the ethical debate would, for conceptual reasons, become less
      polarised.

PMID- 22375082
TI  - The quick and the dead.

PMID- 22375083
TI  - The anatomy of a chromosome.

PMID- 22375084
TI  - The prevalence of thanatophoric dysplasia and lethal osteogenesis imperfecta type
      II in Northern Ireland - a complete population study.
AB  - The minimum prevalence of lethal Osteogenesis imperfecta type II, thanatophoric
      dysplasia and achondroplasia were derived following detailed case note review of
      all perinatal lethal skeletal dysplasias (SD) in Northern Ireland over a 12 year
      period. Multiple sources of ascertainment, including genetic notes, radiological
      reports and post mortem findings, were used. 39 cases were identified.
      Thanatophoric dysplasia was the commonest diagnosis made (22), followed by
      osteogenesis imperfecta type II (four children) and achondroplasia (two
      children). Eleven other diagnoses each occurred once in the 12 year period. The
      minimum prevalence range, per live births, of each of the common skeletal
      dysplasias in Northern Ireland has been calculated; thanatophoric dysplasia
      0.80/10,000, osteogenesis imperfecta type II 0.15/10,000 and achondroplasia
      0.07/10,000. The prevalence range for thanatophoric dysplasia is much higher than
      reported in previous studies. We discuss reasons for the prevalence figures
      obtained.

PMID- 22375085
TI  - Imprint cytology predicts axillary node status in sentinel lymph node biopsy.

PMID- 22375086
TI  - Nicorandil induced penile ulceration.
AB  - We report the unusual complication of penile ulceration caused by Nicorandil, a
      nicotinamide ester used in the treatment of symptomatic angina pectoris.

PMID- 22375087
TI  - Blood and war.
AB  - In 1894 Ulsterman and pathologist Almroth Wright described the citation of blood.
      Twenty-one years later it was introduced into wartime and clinical practice.
      Harvard Medical School had a large part in providing Colonel Andrew Fullerton,
      later Professor of Surgery, Queen's Belfast, with the intellectual and practical
      help for the Allies to deploy blood on the post-Somme Western Front and in
      Salonika. The key investigators and clinicians were Americans and Canadians who
      with Fullerton and Wright instructed the Allies. The key enablers were two
      Harvard-trained surgeons surnamed Robertson-Oswald H. ("Robby") and L. Bruce (no
      relation). Physician Roger I. Lee of Harvard, surgeon George W Crile of
      Cleveland, Peyton Rous of the Rockefeller Institute and Richard Lewisohn of Mount
      Sinai Hospital, both located in the Upper East Side of New York City, played key
      roles.By Armistice in 1918, indirect citrated nutrient-enhanced blood transfusion
      was widely used by the Allies. Geoffrey Keynes was taught the techniques of blood
      transfusion by Dr. Benjamin Harrison Alton of Harvard at a Casualty Clearing
      Station near Albert at the time of the Battle of Passchendaele. Professor "Robby"
      Robertson, DSO, Sir Geoffrey Keynes and Sir Thomas Houston established blood
      banking.

PMID- 22375088
TI  - Recurrent venous thromboses and anti-glomerular basement membrane antibody.

PMID- 22375089
TI  - A case report of 5-fluorouracil-induced coronary artery vasospasm.

PMID- 22375090
TI  - So you want to be a Nephrologist.

PMID- 22375091
TI  - Bayesian Hidden Markov Modeling of Array CGH Data.
AB  - Genomic alterations have been linked to the development and progression of
      cancer. The technique of comparative genomic hybridization (CGH) yields data
      consisting of fluorescence intensity ratios of test and reference DNA samples.
      The intensity ratios provide information about the number of copies in DNA.
      Practical issues such as the contamination of tumor cells in tissue specimens and
      normalization errors necessitate the use of statistics for learning about the
      genomic alterations from array CGH data. As increasing amounts of array CGH data
      become available, there is a growing need for automated algorithms for
      characterizing genomic profiles. Specifically, there is a need for algorithms
      that can identify gains and losses in the number of copies based on statistical
      considerations, rather than merely detect trends in the data.We adopt a Bayesian
      approach, relying on the hidden Markov model to account for the inherent
      dependence in the intensity ratios. Posterior inferences are made about gains and
      losses in copy number. Localized amplifications (associated with oncogene
      mutations) and deletions (associated with mutations of tumor suppressors) are
      identified using posterior probabilities. Global trends such as extended regions
      of altered copy number are detected. Because the posterior distribution is
      analytically intractable, we implement a Metropolis-within-Gibbs algorithm for
      efficient simulation-based inference. Publicly available data on pancreatic
      adenocarcinoma, glioblastoma multiforme, and breast cancer are analyzed, and
      comparisons are made with some widely used algorithms to illustrate the
      reliability and success of the technique.

PMID- 22375092
TI  - Robust EM Continual Reassessment Method in Oncology Dose Finding.
AB  - The continual reassessment method (CRM) is a commonly used dose-finding design
      for phase I clinical trials. Practical applications of this method have been
      restricted by two limitations: (1) the requirement that the toxicity outcome
      needs to be observed shortly after the initiation of the treatment; and (2) the
      potential sensitivity to the prespecified toxicity probability at each dose. To
      overcome these limitations, we naturally treat the unobserved toxicity outcomes
      as missing data, and use the expectation-maximization (EM) algorithm to estimate
      the dose toxicity probabilities based on the incomplete data to direct dose
      assignment. To enhance the robustness of the design, we propose prespecifying
      multiple sets of toxicity probabilities, each set corresponding to an individual
      CRM model. We carry out these multiple CRMs in parallel, across which model
      selection and model averaging procedures are used to make more robust inference.
      We evaluate the operating characteristics of the proposed robust EM-CRM designs
      through simulation studies and show that the proposed methods satisfactorily
      resolve both limitations of the CRM. Besides improving the MTD selection
      percentage, the new designs dramatically shorten the duration of the trial, and
      are robust to the prespecification of the toxicity probabilities.

PMID- 22375093
TI  - Stochastic Generalized Method of Moments.
AB  - The generalized method of moments (GMM) is a very popular estimation and
      inference procedure based on moment conditions. When likelihood-based methods are
      difficult to implement, one can often derive various moment conditions and
      construct the GMM objective function. However, minimization of the objective
      function in the GMM may be challenging, especially over a large parameter space.
      Due to the special structure of the GMM, we propose a new sampling-based
      algorithm, the stochastic GMM sampler, which replaces the multivariate
      minimization problem by a series of conditional sampling procedures. We develop
      the theoretical properties of the proposed iterative Monte Carlo method, and
      demonstrate its superior performance over other GMM estimation procedures in
      simulation studies. As an illustration, we apply the stochastic GMM sampler to a
      Medfly life longevity study. Supplemental materials for the article are available
      online.

PMID- 22375094
TI  - In Silico Prediction of Evolutionarily Conserved GC-Rich Elements Associated with
      Antigenic Proteins of Plasmodium falciparum.
AB  - The Plasmodium falciparum genome being AT-rich, the presence of GC-rich regions
      suggests functional significance. Evolution imposes selection pressure to retain
      functionally important coding and regulatory elements. Hence searching for
      evolutionarily conserved GC-rich, intergenic regions in an AT-rich genome will
      help in discovering new coding regions and regulatory elements. We have used
      elevated GC content in intergenic regions coupled with sequence conservation
      against P. reichenowi, which is evolutionarily closely related to P. falciparum
      to identify potential sequences of functional importance. Interestingly, ~30% of
      the GC-rich, conserved sequences were associated with antigenic proteins encoded
      by var and rifin genes. The majority of sequences identified in the 5' UTR of var
      genes are represented by short expressed sequence tags (ESTs) in cDNA libraries
      signifying that they are transcribed in the parasite. Additionally, 19 sequences
      were located in the 3' UTR of rifins and 4 also have overlapping ESTs. Further
      analysis showed that several sequences associated with var genes have the
      capacity to encode small peptides. A previous report has shown that upstream
      peptides can regulate the expression of var genes hence we propose that these
      conserved GC-rich sequences may play roles in regulation of gene expression.

PMID- 22375095
TI  - Effect of lens status on intraocular pressure in siliconized eyes.
AB  - PURPOSE: To evaluate the effect of lens status on intraocular pressure (IOP) in
      siliconized eyes and also on the emulsification of silicone oil. PATIENTS AND
      METHODS: A total of 31 eyes of 31 patients with retinal detachment were operated
      on with pars plana vitrectomy and silicone oil injection: 16 phakic (Group A) and
      15 pseudophakic (Group B). During the 6-month follow-up period, IOP was measured:
      1 day postoperative, then at 1 week, 1 month, 2 months, 3 months, and 6 months
      postoperative. At the end of the follow-up period, gonioscopy was carried out to
      check emulsified silicone at the anterior chamber angle and also the presence of
      emulsified silicone on the back of the cornea when the patient was lying down.
      RESULTS: There was no significant difference between both groups until the first
      week (P value = 0.15). Starting from the first month, the difference was
      statistically significant, with mean IOPs in Groups A and B of 14.9 mmHg and 18.2
      mmHg, respectively, up to the sixth month (P value = 0.002), with a mean IOP in
      Groups A and B of 14.4 mmHg and 19.4 mmHg, respectively. Emulsified silicone was
      clinically stated in twelve cases (80%) in Group B and in three cases (19%) in
      Group A. CONCLUSION: There is a higher incidence of increased IOP and
      emulsification of silicone oil in pseudophakic eyes than in phakic eyes.

PMID- 22375096
TI  - Effect of photodynamic therapy (PDT), posterior subtenon injection of
      triamcinolone acetonide with PDT, and intravitreal injection of ranibizumab with
      PDT for retinal angiomatous proliferation.
AB  - BACKGROUND: The purpose of this work was to compare the efficacy of photodynamic
      therapy (PDT) with or without posterior subtenon injections of triamcinolone
      acetonide (STA) or intravitreal injections of ranibizumab (IVR) for retinal
      angiomatous proliferation (RAP). METHODS: Thirty-seven eyes from 33 consecutive
      patients with RAP were treated by PDT monotherapy (Group 1), PDT combined with
      STA (Group 2), or PDT combined with IVR (Group 3). The best-corrected visual
      acuity, greatest linear dimension, central retinal thickness, and number of
      treatments were compared among the three groups. RESULTS: The change in mean best
      corrected visual acuity (logMAR) at month 3, 6, and 12 after the initial
      treatment was better in Group 2 (-0.13, -0.23, and -0.21, respectively) and Group
      3 (-0.018, 0.0028, and -0.0067, respectively) than in Group 1 (0.13, 0.19, and
      0.23, respectively); Group 1 versus Group 2 was statistically significant (P =
      0.018). The mean central retinal thickness was reduced from baseline in all
      groups, but the reduction amplitude was significantly greater in Group 2 than in
      Group 1 and Group 3. The mean number of treatments was significantly lower in
      Group 2 (1.1 +/- 0.4) and Group 3 (1.5 +/- 0.5) than in Group 1 (2.9 +/- 0.9) in
      the 12 months after the initial treatment. CONCLUSION: Treatment with STA + PDT
      may be an effective therapy for RAP lesions over 12 months of follow-up.

PMID- 22375097
TI  - Survivin splice variants are not essential for mitotic progression or inhibition
      of apoptosis induced by doxorubicin and radiation.
AB  - Survivin is a critical regulator of mitosis, and an inhibitor of apoptosis which
      is overexpressed in almost all cancers. In the current study, cell cycle profiles
      of normal proliferating human umbilical vein endothelial cells, prostate cancer,
      and lung cancer cell lines expressing varying levels of survivin and its splice
      variants were compared using a novel functional complementation assay. Defects in
      chromosome segregation and cytokinesis that were observed after depletion of
      endogenous survivin were not complemented by any of the survivin splice variants:
      survivin-2B, survivin-3B, survivin-DeltaEx3, or survivin-2A when expressed
      exogenously at a level comparable to endogenous full-length survivin. Survivin
      variants were not detectable at the endogenous protein level. Cancer cells with
      higher levels of full-length survivin and survivin-2B expression, exhibited
      reduced caspase-3 activation following doxorubicin treatment and radiation.
      Whereas earlier studies focused on function and expression levels of survivin
      specific to cancer cells, the current study brings forward the essential role of
      survivin in normal dividing cells. Full-length survivin was found to be
      associated with Aurora-B kinase in the chromosomal passenger complex and
      depletion of survivin mimics mitotic phenotypes observed after Aurora-B kinase
      inhibition, in cancer as well as normal proliferating cells. Thus, our study
      establishes survivin as a marker of proliferation, rather than a cancer specific
      marker. Therefore, systemic therapeutic interventions targeting survivin will
      affect cancer as well as normal proliferating cells.

PMID- 22375098
TI  - Safety and tolerability of exenatide twice daily in patients with type 2
      diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and
      comparator-controlled clinical trials.
AB  - BACKGROUND: Exenatide twice daily is a first-in-class glucagon-like peptide
      receptor agonist approved for the treatment of type 2 diabetes. The objective of
      this analysis was to evaluate the safety profile of exenatide twice daily and to
      compare its profile with that of a pooled comparator (placebo and insulin) in
      patients with type 2 diabetes. METHODS: Data from 19 completed, randomized,
      controlled clinical trials of exenatide twice daily (5 MUg and 10 MUg) were
      pooled and analyzed; the pooled data included 5594 intent-to-treat patients who
      were followed for 12-52 weeks. Incidence rates, exposure-adjusted incidence
      rates, and 95% confidence intervals around risk differences between groups were
      calculated. RESULTS: Baseline demographics and exposure time were comparable
      between groups (exenatide, N = 3261; pooled comparator, N = 2333; mean exposure
      time 166-171 days). Transient, mild- to-moderate nausea was the most frequent
      adverse event with exenatide (36.9% versus 8.3% in the pooled comparator). The
      incidence of hypoglycemia (minor or major) with concomitant sulfonylurea
      (exenatide 26.5%, pooled comparator 20.7%) was higher than that without
      sulfonylurea (exenatide 3.1%, pooled comparator 2.7%) in all groups. Serious
      adverse events, discontinuations due to serious adverse events, and deaths were
      reported with similar frequency in the exenatide and pooled comparator groups.
      Composite exposure-adjusted incidence rates were not statistically different
      between groups for pancreatitis, renal impairment, or major adverse cardiac
      events; there was a difference in incidence rates for benign thyroid neoplasm
      (0.3% versus 0%). CONCLUSION: Overall, this analysis, representing over 1500
      patient-years of exposure, demonstrated that exenatide twice daily was safe and
      generally well tolerated in patients with type 2 diabetes. The incidence of most
      adverse events, including serious adverse events, was similar in both exenatide
      treated and comparator-treated patients. The most distinct differences between
      groups were in gastrointestinal-related adverse events, which is consistent with
      other therapies within the glucagon-like peptide class.

PMID- 22375099
TI  - Dorsal root ganglion - a potential new therapeutic target for neuropathic pain.
AB  - A regional approach can protect our patients from often unacceptable adverse
      effects produced by systematically applied drugs. Regional therapeutic
      approaches, as well as interventions at the level of the peripheral nervous
      system and particularly the dorsal root ganglion (DRG), represent an alternative
      to the systemic application of therapeutic agents. This article provides an
      overview of DRG anatomical peculiarities, explains why the DRG is an important
      therapeutic target, and how animal models of targeted drug delivery can help us
      in the translation of basic research into clinical practice.

PMID- 22375100
TI  - Patterns and correlates of illicit drug selling among youth in the USA.
AB  - PURPOSE: Despite the high rates of drug selling among youth in juvenile justice
      and youth residing in disadvantage neighborhoods, relatively little is known
      about the patterns of illicit drug selling among youth in the general population.
      METHODS: Using the public-use data file from the adolescent sample (N = 17 842)
      in the 2008 National Survey on Drug Use and Health (NSDUH), this study employed
      multiple logistic regression to compare the behavioral, parental involvement, and
      prevention experiences of youth who sold and did not sell illicit drugs in the
      past year.  RESULTS: Findings from a series of logistic regression models
      indicated youth who sold drugs were far more likely to use a wide variety of
      drugs and engage in delinquent acts. Drug-selling youth were significantly less
      likely to report having a parent involved in their life and have someone to talk
      to about serious problems but were more likely to report exposure to drug
      prevention programming.  CONCLUSION: Selling of drugs by youth appears to be a
      byproduct of substance abuse and deviance proneness, and the prevention programs
      these youth experience are likely a result of mandated exposure derived from
      contact with the criminal justice system. Assuming no major drug supply side
      reductions, policies, and practices associated with increasing drug abuse
      treatment, parental involvement and supervision, and school engagement are
      suggested.

PMID- 22375101
TI  - Ten years of integrated care for the older in France.
AB  - BACKGROUND: This paper analyzes progress made toward the integration of the
      French health care system for the older and chronically ill population. POLICIES:
      Over the last 10 years, the French health care system has been principally
      influenced by two competing linkage models that failed to integrate social and
      health care services: local information and coordination centers, governed by the
      social field, and the gerontological health networks governed by the health
      field. In response to this fragmentation, Homes for the Integration and Autonomy
      for Alzheimer patients (MAIAs) is currently being implemented at experimental
      sites in the French national Alzheimer plan, using an evidence-based model of
      integrated care. In addition, the state's reforms recently created regional
      health agencies (ARSs) by merging seven strategic institutions to manage the
      overall delivery of care. CONCLUSION: The French health care system is moving
      from a linkage-based model to a more integrated care system. We draw some early
      lessons from these changes, including the importance of national leadership and
      governance and a change management strategy that uses both top-down and bottom-up
      approaches to implement these reforms.

PMID- 22375103
TI  - Evolution and functional diversity of the Calcium Binding Proteins (CaBPs).
AB  - The mammalian central nervous system (CNS) exhibits a remarkable ability to
      process, store, and transfer information. Key to these activities is the use of
      highly regulated and unique patterns of calcium signals encoded by calcium
      channels and decoded by families of specific calcium-sensing proteins. The
      largest family of eukaryotic calcium sensors is those related to the small EF
      hand containing protein calmodulin (CaM). In order to maximize the usefulness of
      calcium as a signaling species and to permit the evolution and fine tuning of the
      mammalian CNS, families of related proteins have arisen that exhibit
      characteristic calcium binding properties and tissue-, cellular-, and sub
      cellular distribution profiles. The Calcium Binding Proteins (CaBPs) represent
      one such family of vertebrate specific CaM like proteins that have emerged in
      recent years as important regulators of essential neuronal target proteins.
      Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and
      that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct
      intracellular localizations based on different targeting mechanisms including a
      novel type-II transmembrane domain in CaBPs 7 and 8 (otherwise known as calneuron
      II and calneuron I, respectively). Recent work has led to the identification of
      new target interactions and possible functions for the CaBPs suggesting that they
      have multiple physiological roles with relevance for the normal functioning of
      the CNS.

PMID- 22375105
TI  - GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene
      targeted mice.
AB  - The GluA2 subunit in heteromeric alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor channels restricts Ca(2+) permeability
      and block by polyamines, rendering linear the current-voltage relationship of
      these glutamate-gated cation channels. Although GluA2-lacking synaptic AMPA
      receptors occur in GABA-ergic inhibitory neurons, hippocampal CA1 pyramidal cell
      synapses are widely held to feature only GluA2 containing AMPA receptors. A
      controversy has arisen from reports of GluA2-lacking AMPA receptors at
      hippocampal CA3-to-CA1 cell synapses and a study contesting these findings. Here
      we sought independent evidence for the presence of GluA2-lacking AMPA receptors
      in CA1 pyramidal cell synapses by probing the sensitivity of their gated cation
      channels in wild-type (WT) mice and gene-targeted mouse mutants to
      philanthotoxin, a specific blocker of GluA2-lacking AMPA receptors. The mutants
      either lacked GluA2 for maximal philanthotoxin sensitivity, or, for minimal
      sensitivity, expressed GluA1 solely in a Q/R site-edited version or not at all.
      Our comparative electrophysiological analyses provide incontrovertible evidence
      for the presence in wild-type CA1 pyramidal cell synapses of GluA2-less AMPA
      receptor channels. This article is part of a Special Issue entitled "Calcium
      permeable AMPARs in synaptic plasticity and disease."

PMID- 22375106
TI  - Deep brain stimulation for movement disorders - a history of success and
      challenges to conquer.

PMID- 22375102
TI  - Strategies for the preparation of bifunctional gadolinium(III) chelators.
AB  - The development of gadolinium chelators that can be easily and readily linked to
      various substrates is of primary importance for the development high relaxation
      efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over
      the last 25 years a large number of bifunctional chelators have been prepared.
      For the most part, these compounds are based on ligands that are already used in
      clinically approved contrast agents. More recently, new bifunctional chelators
      have been reported based on complexes that show a more potent relaxation effect,
      faster complexation kinetics and in some cases simpler synthetic procedures. This
      review provides an overview of the synthetic strategies used for the preparation
      of bifunctional chelators for MRI applications.

PMID- 22375104
TI  - The visinin-like proteins VILIP-1 and VILIP-3 in Alzheimer's disease-old wine in
      new bottles.
AB  - The neuronal Ca(2+)-sensor (NCS) proteins VILIP-1 and VILIP-3 have been
      implicated in the etiology of Alzheimer's disease (AD). Genome-wide association
      studies (GWAS) show association of genetic variants of VILIP-1 (VSNL1) and VILIP
      3 (HPCAL1) with AD+P (+psychosis) and late onset AD (LOAD), respectively. In AD
      brains the expression of VILIP-1 and VILIP-3 protein and mRNA is down-regulated
      in cortical and limbic areas. In the hippocampus, for instance, reduced VILIP-1
      mRNA levels correlate with the content of neurofibrillary tangles (NFT) and
      amyloid plaques, the pathological characteristics of AD, and with the mini mental
      state exam (MMSE), a test for cognitive impairment. More recently, VILIP-1 was
      evaluated as a cerebrospinal fluid (CSF) biomarker and a prognostic marker for
      cognitive decline in AD. In CSF increased VILIP-1 levels correlate with levels of
      Abeta, tau, ApoE4, and reduced MMSE scores. These findings tie in with previous
      results showing that VILIP-1 is involved in pathological mechanisms of altered
      Ca(2+)-homeostasis leading to neuronal loss. In PC12 cells, depending on co
      expression with the neuroprotective Ca(2+)-buffer calbindin D28K, VILIP-1
      enhanced tau phosphorylation and cell death. On the other hand, VILIP-1 affects
      processes, such as cyclic nucleotide signaling and dendritic growth, as well as
      nicotinergic modulation of neuronal network activity, both of which regulate
      synaptic plasticity and cognition. Similar to VILIP-1, its interaction partner
      alpha4beta2 nicotinic acetylcholine receptor (nAChR) is severely reduced in AD,
      causing severe cognitive deficits. Comparatively little is known about VILIP-3,
      but its interaction with cytochrome b5, which is part of an antioxidative system
      impaired in AD, hint toward a role in neuroprotection. A current hypothesis is
      that the reduced expression of visinin-like protein (VSNLs) in AD is caused by
      selective vulnerability of subpopulations of neurons, leading to the death of
      these VILIP-1-expressing neurons, explaining its increased CSF levels. While the
      Ca(2+)-sensor appears to be a good biomarker for the detrimental effects of Abeta
      in AD, its early, possibly Abeta-induced, down-regulation of expression may
      additionally attenuate neuronal signal pathways regulating the functions of
      dendrites and neuroplasticity, and as a consequence, this may contribute to
      cognitive decline in early AD.

PMID- 22375108
TI  - Binocular interactions underlying the classic optomotor responses of flying
      flies.
AB  - In response to imposed course deviations, the optomotor reactions of animals
      reduce motion blur and facilitate the maintenance of stable body posture. In
      flies, many anatomical and electrophysiological studies suggest that disparate
      motion cues stimulating the left and right eyes are not processed in isolation
      but rather are integrated in the brain to produce a cohesive panoramic percept.
      To investigate the strength of such inter-ocular interactions and their role in
      compensatory sensory-motor transformations, we utilize a virtual reality flight
      simulator to record wing and head optomotor reactions by tethered flying flies in
      response to imposed binocular rotation and monocular front-to-back and back-to
      front motion. Within a narrow range of stimulus parameters that generates large
      contrast insensitive optomotor responses to binocular rotation, we find that
      responses to monocular front-to-back motion are larger than those to panoramic
      rotation, but are contrast sensitive. Conversely, responses to monocular back-to
      front motion are slower than those to rotation and peak at the lowest tested
      contrast. Together our results suggest that optomotor responses to binocular
      rotation result from the influence of non-additive contralateral inhibitory as
      well as excitatory circuit interactions that serve to confer contrast
      insensitivity to flight behaviors influenced by rotatory optic flow.

PMID- 22375107
TI  - Posterior parietal cortex and long-term memory: some data from laboratory
      animals.
AB  - The posterior parietal cortex (PPC) was long viewed as just involved in the
      perception of spatial relationships between the body and its surroundings and of
      movements related to them. In recent years the PPC has been shown to participate
      in many other cognitive processes, among which working memory and the
      consolidation and retrieval of episodic memory. The neurotransmitter and other
      molecular processes involved have been determined to a degree in rodents. More
      research will no doubt determine the extent to which these findings can be
      extrapolated to primates, including humans. In these there appears to be a
      paradox: imaging studies strongly suggest an important participation of the PPC
      in episodic memory, whereas lesion studies are much less suggestive, let alone
      conclusive. The data on the participation of the PPC in episodic memory so far do
      not permit any conclusion as to what aspect of consolidation and retrieval it
      handles in addition to those dealt with by the hippocampus and basolateral
      amygdala, if any.

PMID- 22375109
TI  - Functional connectivity studies of patients with auditory verbal hallucinations.
AB  - Functional connectivity (FC) studies of brain mechanisms leading to auditory
      verbal hallucinations (AVHs) utilizing functional magnetic resonance imaging
      (fMRI) data are reviewed. Initial FC studies utilized fMRI data collected during
      performance of various tasks, which suggested frontotemporal disconnection and/or
      source-monitoring disturbances. Later FC studies have utilized resting (no-task)
      fMRI data. These studies have produced a mixed picture of disconnection and
      hyperconnectivity involving different pathways associated with AVHs. Results of
      our most recent FC study of AVHs are reviewed in detail. This study suggests that
      the core mechanism producing AVHs involves not a single pathway, but a more
      complex functional loop. Components of this loop include Wernicke's area and its
      right homologue, the left inferior frontal cortex, and the putamen. It is
      noteworthy that the putamen appears to play a critical role in the generation of
      spontaneous language, and in determining whether auditory stimuli are registered
      consciously as percepts. Excessive functional coordination linking this region
      with the Wernicke's seed region in patients with schizophrenia could, therefore,
      generate an overabundance of potentially conscious language representations. In
      our model, intact FC in the other two legs of corticostriatal loop (Wernicke's
      with left IFG, and left IFG with putamen) appeared to allow hyperconnectivity
      linking the putamen and Wernicke's area (common to schizophrenia overall) to be
      expressed as conscious hallucinations of speech. Recommendations for future
      studies are discussed, including inclusion of multiple methodologies applied to
      the same subjects in order to compare and contrast different mechanistic
      hypotheses, utilizing EEG to better parse time-course of neural synchronization
      leading to AVHs, and ascertaining experiential subtypes of AVHs that may reflect
      distinct mechanisms.

PMID- 22375110
TI  - Individual differences in distraction by motion predicted by neural activity in
      MT/V5.
AB  - Individuals differ substantially in their susceptibility to distraction by
      irrelevant visual information. Previous research has uncovered how individual
      variability in the goal-driven component of attentional control influences
      distraction, yet it remains unknown whether other sources of variability between
      individuals also predict distraction. In this fMRI study, we showed that an
      individual's inherent sensitivity to passively viewed visual motion predicts
      his/her susceptibility to distraction by motion. Bilateral MT/V5 was localized in
      participants during passive viewing of moving stimuli, affording a baseline
      measure of motion sensitivity. Next, participants performed a visual search task
      with an irrelevant motion singleton distractor, and both behavioral and neural
      indices of distraction were recorded. Results revealed that both of these indices
      were predicted by the independent index of motion sensitivity. An additional
      analysis of moment-to-moment fluctuations in distraction within individuals
      revealed that distraction could be predicted by pretrial fMRI activity in several
      brain regions, including MT+, which likely reflected the observer's momentary
      propensity to process motion. Together, these results shed light on how
      variability in factors other than goal-driven processing, both within and between
      individuals, affects attentional control and one's perception of the visual
      world.

PMID- 22375111
TI  - The neural correlates of the body-object interaction effect in semantic
      processing.
AB  - The semantic richness dimension referred to as body-object interaction (BOI)
      measures perceptions of the ease with which people can physically interact with
      words' referents. Previous studies have shown facilitated lexical and semantic
      processing for words rated high in BOI, e.g., belt, than for words rated low in
      BOI, e.g., sun. These BOI effects have been taken as evidence that embodied
      information is relevant to word recognition (Siakaluk et al., 2008a). However, to
      date there is no evidence linking BOI manipulations to differences in the
      utilization of perceptual or sensorimotor areas of the brain. The current study
      used event-related functional magnetic resonance imaging (fMRI) to examine the
      neural correlates of BOI in a semantic categorization task (SCT). Sixteen healthy
      adults participated. Results showed that high BOI words were associated with
      activation in the left inferior parietal lobule (supramarginal gyrus, BA 40), a
      sensory association area involved in kinesthetic memory. These results provide
      evidence that the BOI dimension captures the relative availability of
      sensorimotor information, and that this contributes to semantic processing.

PMID- 22375112
TI  - How do auditory verbal hallucinations in patients differ from those in non
      patients?
AB  - Auditory verbal hallucinations (AVHs) are experienced by individuals with various
      clinical diagnoses, such as psychosis, but also a significant minority of healthy
      individuals from the general population may experience them. Although much
      research has been carried out the past few decades, the mechanisms and factors
      underlying the emergence of AVHs is still poorly understood. One way of
      clarifying this issue involves comparing AVHs in patient and non-patient
      populations. In particular, differences between these groups will provide
      important information concerning the emergence of AVHs. After a general
      presentation and discussion of the notion of a continuum hypothesis, studies
      comparing patients with non-patients experiencing AVHs will be reviewed. This
      will comprise studies examining the phenomenological characteristics of AVHs in
      addition to neuroimaging and cognitive studies. Although we are beginning to
      elucidate important differences on a phenomenological level between these two
      types of AVHs, far too few studies have directly compared patient and non-patient
      AVHs in terms of underlying cerebral correlates and cognitive mechanisms.
      Nevertheless, and based on recent research on phenomenological differences, two
      issues stand out that need to be addressed, namely, the highly negative emotional
      content of AVHs in patients and the early onset of AVHs in non-patients
      populations. Suggestions for future research will be discussed.

PMID- 22375113
TI  - Searching for roots of entrainment and joint action in early musical
      interactions.
AB  - When people play music and dance together, they engage in forms of musical joint
      action that are often characterized by a shared sense of rhythmic timing and
      affective state (i.e., temporal and affective entrainment). In order to
      understand the origins of musical joint action, we propose a model in which
      entrainment is linked to dual mechanisms (motor resonance and action simulation),
      which in turn support musical behavior (imitation and complementary joint
      action). To illustrate this model, we consider two generic forms of joint musical
      behavior: chorusing and turn-taking. We explore how these common behaviors can be
      founded on entrainment capacities established early in human development,
      specifically during musical interactions between infants and their caregivers. If
      the roots of entrainment are found in early musical interactions which are
      practiced from childhood into adulthood, then we propose that the rehearsal of
      advanced musical ensemble skills can be considered to be a refined, mimetic form
      of temporal and affective entrainment whose evolution begins in infancy.

PMID- 22375114
TI  - A selective review of multimodal fusion methods in schizophrenia.
AB  - Schizophrenia (SZ) is one of the most cryptic and costly mental disorders in
      terms of human suffering and societal expenditure (van Os and Kapur, 2009).
      Though strong evidence for functional, structural, and genetic abnormalities
      associated with this disease exists, there is yet no replicable finding which has
      proven accurate enough to be useful in clinical decision making (Fornito et al.,
      2009), and its diagnosis relies primarily upon symptom assessment (Williams et
      al., 2010a). It is likely in part that the lack of consistent neuroimaging
      findings is because most models favor only one data type or do not combine data
      from different imaging modalities effectively, thus missing potentially important
      differences which are only partially detected by each modality (Calhoun et al.,
      2006a). It is becoming increasingly clear that multimodal fusion, a technique
      which takes advantage of the fact that each modality provides a limited view of
      the brain/gene and may uncover hidden relationships, is an important tool to help
      unravel the black box of schizophrenia. In this review paper, we survey a number
      of multimodal fusion applications which enable us to study the schizophrenia
      macro-connectome, including brain functional, structural, and genetic aspects and
      may help us understand the disorder in a more comprehensive and integrated
      manner. We also provide a table that characterizes these applications by the
      methods used and compare these methods in detail, especially for multivariate
      models, which may serve as a valuable reference that helps readers select an
      appropriate method based on a given research question.

PMID- 22375115
TI  - Inhibition of return is no hallmark of exogenous capture by unconscious cues.
AB  - Inhibition of irrelevant information and response tendencies is a central
      characteristic of conscious control and executive functions. However, recent
      theories in vision considered Inhibition of Return (IOR: slower responses to
      attended than unattended positions) to be a hallmark of automatic exogenous
      capture of visual attention by unconscious cues. In the present study, we show
      that an unconscious cue that exogenously captures attention does not lead to IOR.
      First of all, subliminal cues with a contrast different from a searched-for
      target contrast capture attention independently of their match of contrast
      polarity to the search criteria. This is found with a short cue-target interval
      (Exp. 1). However, the same cues do not lead to IOR with a long cue-target
      interval. The lack of IOR is also verified for several intermediate intervals
      (Exp. 2), for high-contrast cues and low-contrast targets (Exp. 3), and with
      lower luminance cues presented on a CRT screen (Exp. 4). Finally, no capture
      effect but IOR is found for consciously perceived anti-predictive cues (Exp. 5).
      Together the results support the notion of a double dissociation between IOR and
      exogenous capture and are in line with a decisive role of consciousness for
      inhibition.

PMID- 22375116
TI  - Oxytocin and mutual communication in mother-infant bonding.
AB  - Mother-infant bonding is universal to all mammalian species. In this review, we
      describe the manner in which reciprocal communication between the mother and
      infant leads to mother-infant bonding in rodents. In rats and mice, mother-infant
      bond formation is reinforced by various social stimuli, such as tactile stimuli
      and ultrasonic vocalizations (USVs) from the pups to the mother, and feeding and
      tactile stimulation from the mother to the pups. Some evidence suggests that
      mother and infant can develop a cross-modal sensory recognition of their
      counterpart during this bonding process. Neurochemically, oxytocin in the neural
      system plays a pivotal role in each side of the mother-infant bonding process,
      although the mechanisms underlying bond formation in the brains of infants has
      not yet been clarified. Impairment of mother-infant bonding, that is, deprivation
      of social stimuli from the mother, strongly influences offspring sociality,
      including maternal behavior toward their own offspring in their adulthood,
      implying a "non-genomic transmission of maternal environment," even in rodents.
      The comparative understanding of cognitive functions between mother and infants,
      and the biological mechanisms involved in mother-infant bonding may help us
      understand psychiatric disorders associated with mother-infant relationships.

PMID- 22375117
TI  - Functional significance of the emotion-related late positive potential.
AB  - The late positive potential (LPP) is an event-related potential (ERP) component
      over visual cortical areas that is modulated by the emotional intensity of a
      stimulus. However, the functional significance of this neural modulation remains
      elusive. We conducted two experiments in which we studied the relation between
      LPP amplitude, subsequent perceptual sensitivity to a non-emotional stimulus
      (Experiment 1) and visual cortical excitability, as reflected by P1/N1 components
      evoked by this stimulus (Experiment 2). During the LPP modulation elicited by
      unpleasant stimuli, perceptual sensitivity was not affected. In contrast, we
      found some evidence for a decreased N1 amplitude during the LPP modulation, a
      decreased P1 amplitude on trials with a relatively large LPP, and consistent
      negative (but non-significant) across-subject correlations between the magnitudes
      of the LPP modulation and corresponding changes in d-prime or P1/N1 amplitude.
      The results provide preliminary evidence that the LPP reflects a global
      inhibition of activity in visual cortex, resulting in the selective survival of
      activity associated with the processing of the emotional stimulus.

PMID- 22375118
TI  - Left-shifted nav channels in injured bilayer: primary targets for neuroprotective
      nav antagonists?
AB  - Mechanical, ischemic, and inflammatory injuries to voltage-gated sodium channel
      (Nav)-rich membranes of axon initial segments and nodes of Ranvier render Nav
      channels dangerously leaky. By what means? The behavior of recombinant Nav1.6
      (Wang et al., 2009) leads us to postulate that, in neuropathologic conditions,
      structural degradation of axolemmal bilayer fosters chronically left-shifted Nav
      channel operation, resulting in E(Na) rundown. This "sick excitable cell Nav
      leak" would encompass left-shifted fast- and slow-mode based persistent I(Na)
      (i.e., I(window) and slow-inactivating I(Na)). Bilayer-damage-induced
      electrophysiological dysfunctions of native-Nav channels, and effects on
      inhibitors on those channels, should, we suggest, be studied in myelinated axons,
      exploiting I(Na)(V,t) hysteresis data from sawtooth ramp clamp. We hypothesize
      that (like dihydropyridines for Ca channels), protective lipophilic Nav
      antagonists would partition more avidly into disorderly bilayers than into the
      well-packed bilayers characteristic of undamaged, healthy plasma membrane.
      Whereas inhibitors using aqueous routes would access all Navs equally,
      differential partitioning into "sick bilayer" would co-localize lipophilic
      antagonists with "sick-Nav channels," allowing for more specific targeting of
      impaired cells. Molecular fine-tuning of Nav antagonists to favor more avid
      partitioning into damaged than into intact bilayers could reduce side effects. In
      potentially salvageable neurons of traumatic and/or ischemic penumbras, in
      inflammatory neuropathies, in muscular dystrophy, in myocytes of cardiac infarct
      borders, Nav-leak driven excitotoxicity overwhelms cellular repair mechanisms.
      Precision-tuning of a lipophilic Nav antagonist for greatest efficacy in mildly
      damaged membranes could render it suitable for the prolonged continuous
      administration needed to allow for the remodeling of the excitable membranes, and
      thus functional recovery.

PMID- 22375120
TI  - A unified point process probabilistic framework to assess heartbeat dynamics and
      autonomic cardiovascular control.
AB  - In recent years, time-varying inhomogeneous point process models have been
      introduced for assessment of instantaneous heartbeat dynamics as well as specific
      cardiovascular control mechanisms and hemodynamics. Assessment of the model's
      statistics is established through the Wiener-Volterra theory and a multivariate
      autoregressive (AR) structure. A variety of instantaneous cardiovascular metrics,
      such as heart rate (HR), heart rate variability (HRV), respiratory sinus
      arrhythmia (RSA), and baroreceptor-cardiac reflex (baroreflex) sensitivity (BRS),
      are derived within a parametric framework and instantaneously updated with
      adaptive and local maximum likelihood estimation algorithms. Inclusion of second
      order non-linearities, with subsequent bispectral quantification in the frequency
      domain, further allows for definition of instantaneous metrics of non-linearity.
      We here present a comprehensive review of the devised methods as applied to
      experimental recordings from healthy subjects during propofol anesthesia.
      Collective results reveal interesting dynamic trends across the different
      pharmacological interventions operated within each anesthesia session, confirming
      the ability of the algorithm to track important changes in cardiorespiratory
      elicited interactions, and pointing at our mathematical approach as a promising
      monitoring tool for an accurate, non-invasive assessment in clinical practice. We
      also discuss the limitations and other alternative modeling strategies of our
      point process approach.

PMID- 22375119
TI  - The role of chemokines in mediating graft versus host disease: opportunities for
      novel therapeutics.
AB  - Bone marrow transplantation (BMT) is the current therapy of choice for several
      malignancies and severe autoimmune diseases. Graft versus host disease (GVHD) is
      the major complication associated with BMT. T lymphocytes and other leukocytes
      migrate into target organs during GVHD, become activated and mediate tissue
      damage. Chemokines are well known inducers of leukocyte trafficking and
      activation and contribute to the pathogenesis of GVHD. Here, we review the major
      animal models used to study GVHD and the role of chemokines in mediating tissue
      damage in these models. The role of these molecules in promoting potential
      beneficial effects of the graft, especially graft versus leukemia, is also
      discussed. Finally, the various pharmacological strategies to block the chemokine
      system or downstream signaling events in the context of GVHD are discussed.

PMID- 22375121
TI  - Intestinal mucosal triacylglycerol accumulation secondary to decreased lipid
      secretion in obese and high fat fed mice.
AB  - The ectopic deposition of fat in liver and muscle during obesity is well
      established, however surprisingly little is known about the intestine. We used
      the ob/ob mouse and C57BL6/J mice fed a high fat (HF) diet to examine the effects
      of obesity and the effects of HF feeding, respectively, on intestinal mucosal
      triacylglycerol (TG) accumulation. Male C57BL6/J (wild-type, WT) mice were fed
      low fat (LF; 10% kcal as fat) or HF (45%) diets, and ob/ob mice were fed the LF
      diet, for 3 weeks. In this time frame, the WT-HF mice did not become obese,
      enabling independent examination of effects of the HF diet and effects of
      obesity. Analysis of intestinal lipid extracts from fed and fasted animals
      demonstrated that the mucosa, like other tissues, accumulates excess lipid. In
      the fed state, mucosal triacylglycerol (TG) levels were threefold and fivefold
      higher in the WT-HF and ob/ob mice, respectively, relative to the WT-LF mice. In
      the fasted state, mucosa from ob/ob mice had threefold higher TG levels relative
      to WT-LF mucosa. q-PCR analysis of mucosal mRNA from fed state mice showed
      alterations in the expression of several genes related to both anabolic and
      catabolic lipid metabolism pathways in WT-HF and ob/ob mice relative to WT-LF
      controls. Fewer changes were found in mucosal samples from the fasted state
      animals. Remarkably, oral fat tolerance tests showed a striking reduction in the
      plasma appearance of an oral fat load in the ob/ob and WT-HF mice compared to WT
      LF. Overall, the results demonstrate that the intestinal mucosa accumulates
      excess TG during obesity. Changes in the expression of lipid metabolic and
      transport genes, as well as reduced secretion of dietary lipid from the mucosal
      cells into the circulation, may contribute to the TG accumulation in intestinal
      mucosa during obesity. Moreover, even in the absence of frank obesity, HF feeding
      leads to a large decrease in the rate of intestinal lipid secretion.

PMID- 22375122
TI  - Reduced triglyceride secretion in response to an acute dietary fat challenge in
      obese compared to lean mice.
AB  - Obesity results in abnormally high levels of triglyceride (TG) storage in tissues
      such as liver, heart, and muscle, which disrupts their normal functions.
      Recently, we found that lean mice challenged with high levels of dietary fat
      store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine,
      enterocytes, and that this storage increases and then decreases over time after
      an acute dietary fat challenge. The goal of this study was to investigate the
      effects of obesity on intestinal TG metabolism. More specifically we asked
      whether TG storage in and secretion from the intestine are altered in obesity. We
      investigated these questions in diet-induced obese (DIO) and leptin-deficient
      (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice
      compared to lean mice in the fed state, but similar levels of TG storage after a
      6-h fast. In addition, we found similar TG storage in the intestine of lean and
      DIO mice at multiple time points after an acute dietary fat challenge.
      Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice
      compared to lean controls in response to an acute dietary fat challenge.
      Furthermore, we found altered mRNA levels for genes involved in regulation of
      intestinal TG metabolism in lean and DIO mice at 6 h fasting and in response to
      an acute dietary fat challenge. More specifically, we found that many of the
      genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis
      were induced in response to an acute dietary fat challenge in lean mice, but this
      induction was not observed in DIO mice. In fact, we found a significant decrease
      in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation
      in DIO mice in response to an acute dietary fat challenge. Our findings
      demonstrate altered TG handling by the small intestine of obese compared to lean
      mice.

PMID- 22375123
TI  - Cardiac and Metabolic Physiology of Early Larval Zebrafish (Danio rerio) Reflects
      Parental Swimming Stamina.
AB  - Swimming stamina in adult fish is heritable, it is unknown if inherited traits
      that support enhanced swimming stamina in offspring appear only in juveniles
      and/or adults, or if these traits actually appear earlier in the morphologically
      quite different larvae. To answer this question, mature adult zebrafish (Danio
      rerio) were subjected to a swimming performance test that allowed separation into
      low swimming stamina or high swimming stamina groups. Adults were then bred
      within their own performance groups. Larval offspring from each of the two
      groups, designated high (L(HSD)) and low stamina-derived larvae (L(LSD)), were
      then reared at 27 degrees C in aerated water (21% O(2)). Routine (f(H),r) and
      active (f(H),a) heart rate, and routine [Formula: see text] and active [Formula:
      see text] mass-specific oxygen consumption were recorded from 5 days post
      fertilization (dpf) through 21 dpf, and gross cost of transport and factorial
      aerobic metabolic scope were derived from [Formula: see text] measurements. Heart
      rate generally ranged between 150 and 225 bpm in both L(HSD) and L(LSD)
      populations. However, significant (P < 0.05) differences existed between the
      L(LSD) and L(HSD) populations at 5 and 14 dpf in f(H),r and at days 10 and 15 dpf
      in f(H),a. [Formula: see text] was 0.04-0.32 MUmol mg(-1) h(-1), while [Formula:
      see text] was 0.2-1.2 MUmol mg(-1) h(-1). Significant (P < 0.05) differences
      between the L(LSD) and L(HSD) populations in [Formula: see text] occurred at 7,
      10, and 21 dpf and in [Formula: see text] at 7 dpf. Gross cost of transport was
      ~6-10 MUmol O(2).MUg(-1) m(-1) at 5 dpf, peaking at 14-19 MUmol O(2) MUg(-1) m(
      1) at 7-10 dpf, before falling again to 5-6 MUmol O(2) MUg(-1) m(-1) at 21 dpf,
      with gross cost of transport significantly higher in the L(LSD) population at 7
      dpf. Collectively, these data indicate that inherited physiological differences
      known to contribute to enhanced stamina in adult parents also appear in their
      larval offspring well before attainment of juvenile or adult features.

PMID- 22375125
TI  - The sarcomeric protein nebulin: another multifunctional giant in charge of muscle
      strength optimization.
AB  - The sliding filament model of the sarcomere was developed more than half a
      century ago. This model, consisting only of thin and thick filaments, has been
      successful in explaining many, but not all, features of skeletal muscle. Work
      during the 1980s revealed the existence of two additional filaments: the giant
      filamentous proteins titin and nebulin. Whereas the role of titin rapidly
      progressed, nebulin's role in muscle structure and function remained long
      nebulous. An important feature of muscle structure and function that has remained
      relatively obscure concerns the mechanisms that are involved in regulating thin
      filament length. Filament length is an important aspect of muscle function as
      force production is proportional to the amount of overlap between thick and thin
      filaments. Recent advances, due in part to the generation of nebulin KO models,
      reveal that nebulin plays an important role in the regulation of thin filament
      length, most likely by stabilizing F-actin assemblies. Another structural feature
      of skeletal muscle that has been incompletely understood concerns the mechanisms
      involved in maintaining Z-disk structure and the regular lateral alignment of
      adjacent sarcomeres during contraction. Recent studies indicate that nebulin is
      part of a protein complex that mechanically links adjacent myofibrils. In
      addition to these structural roles in support of myofibrillar force generation,
      nebulin has been also shown to regulate directly muscle contraction at the level
      of individual crossbridges: cycling kinetics and the calcium sensitivity of force
      producing crossbridges is enhanced in the presence of nebulin. Thus, these recent
      data all point to nebulin being important for muscle force optimization.
      Consequently, muscle weakness as the lead symptom develops in the case of
      patients with nemaline myopathy that have mutations in the nebulin gene. Here, we
      discuss these important novel insights into the role of nebulin in skeletal
      muscle function.

PMID- 22375126
TI  - Central versus peripheral cardiovascular risk in metabolic syndrome.
AB  - Individuals with metabolic syndrome (MetS; i.e., three of five of the following
      risk factors (RFs): elevated blood pressure, waist circumference, triglycerides,
      blood glucose, or reduced HDL) are thought to be prone to serious cardiovascular
      disease and there is debate as to whether the disease begins in the peripheral
      vasculature or centrally. This study investigates hemodynamics, cardiac
      function/morphology, and mechanical properties of the central (heart, carotid
      artery) or peripheral [total peripheral resistance (TPR), forearm vascular bed]
      vasculature in individuals without (1-2 RFs: n = 28), or with (>=3 RFs: n = 46)
      MetS. After adjustments for statin and blood pressure medication use, those with
      MetS had lower mitral valve E/A ratios (<3 RFs: 1.24 +/- 0.07; >=3 RFs: 1.01 +/-
      0.04; P = 0.025), and higher TPR index (<3 RFs: 48 +/- 2 mmHg/L/min/m(2); >=3
      RFs: 53 +/- 2 mmHg/L/min/m(2); P = 0.04). There were no differences in heart
      size, carotid artery measurements, cardiovagal baroreflex, pulse-wave velocity,
      stroke volume index, or cardiac output index due to MetS after adjustments for
      statin and blood pressure medication use. The use of statins was associated with
      increased inertia in the brachial vascular bed, increased HbA1c and decreased LDL
      cholesterol. The independent use of anti-hypertensive medication was associated
      with decreased predicted [Formula: see text] triglycerides, diastolic blood
      pressure, interventricular septum thickness, calculated left ventricle mass, left
      ventricle posterior wall thickness, and left ventricle pre-ejection period, but
      increased carotid stiffness, HDL cholesterol, and heart rate. These data imply
      that both a central cardiac effect and a peripheral effect of vascular resistance
      are expressed in MetS. These data also indicate that variance in between-group
      responses due to pharmacological treatments are important factors to consider in
      studying cardiovascular changes in these individuals.

PMID- 22375124
TI  - Loss of proteostatic control as a substrate for atrial fibrillation: a novel
      target for upstream therapy by heat shock proteins.
AB  - Atrial fibrillation (AF) is the most common, sustained clinical tachyarrhythmia
      associated with significant morbidity and mortality. AF is a persistent condition
      with progressive structural remodeling of the atrial cardiomyocytes due to the AF
      itself, resulting in cellular changes commonly observed in aging and in other
      heart diseases. While rhythm control by electrocardioversion or drug treatment is
      the treatment of choice in symptomatic AF patients, its efficacy is still
      limited. Current research is directed at preventing first-onset AF by limiting
      the development of substrates underlying AF progression and resembles mechanism
      based therapy. Upstream therapy refers to the use of non-ion channel anti
      arrhythmic drugs that modify the atrial substrate- or target-specific mechanisms
      of AF, with the ultimate aim to prevent the occurrence (primary prevention) or
      recurrence of the arrhythmia following (spontaneous) conversion (secondary
      prevention). Heat shock proteins (HSPs) are molecular chaperones and comprise a
      large family of proteins involved in the protection against various forms of
      cellular stress. Their classical function is the conservation of proteostasis via
      prevention of toxic protein aggregation by binding to (partially) unfolded
      proteins. Our recent data reveal that HSPs prevent electrical, contractile, and
      structural remodeling of cardiomyocytes, thus attenuating the AF substrate in
      cellular, Drosophila melanogaster, and animal experimental models. Furthermore,
      studies in humans suggest a protective role for HSPs against the progression from
      paroxysmal AF to persistent AF and in recurrence of AF. In this review, we
      discuss upregulation of the heat shock response system as a novel target for
      upstream therapy to prevent derailment of proteostasis and consequently
      progression and recurrence of AF.

PMID- 22375127
TI  - The Inert vs. the Living State of Matter: Extended Criticality, Time Geometry,
      Anti-Entropy - An Overview.
AB  - The physical singularity of life phenomena is analyzed by means of comparison
      with the driving concepts of theories of the inert. We outline conceptual
      analogies, transferals of methodologies and theoretical instruments between
      physics and biology, in addition to indicating significant differences and
      sometimes logical dualities. In order to make biological phenomenalities
      intelligible, we introduce theoretical extensions to certain physical theories.
      In this synthetic paper, we summarize and propose a unified conceptual framework
      for the main conclusions drawn from work spanning a book and several articles,
      quoted throughout.

PMID- 22375128
TI  - Clinical application of heart rate variability after acute myocardial infarction.
AB  - Heart rate (HR) variability has been extensively studied in patients surviving an
      acute myocardial infarction (AMI). The majority of studies have shown that
      patients with reduced or abnormal HR variability/turbulence have an increased
      risk of mortality within few years after an AMI. Various measures of HR dynamics,
      such as time-domain, spectral, and non-linear measures of HR variability, as well
      as HR turbulence, have been used in risk stratification of post-AMI patients. The
      prognostic power of various measures, except of those reflecting rapid R-R
      interval oscillations, has been almost identical, albeit some non-linear HR
      variability measures, such as short-term fractal scaling exponent, and HR
      turbulence, have provided somewhat better prognostic information than the others.
      Abnormal HR variability predicts both sudden and non-sudden cardiac death after
      AMI. Because of remodeling of the arrhythmia substrate after AMI, early
      measurement of HR variability to identify those at high risk should likely be
      repeated later in order to assess the risk of fatal arrhythmia events. Future
      randomized trials using HR variability/turbulence as one of the pre-defined
      inclusion criteria will show whether routine measurement of HR
      variability/turbulence will become a routine clinical tool for risk
      stratification of post-AMI patients.

PMID- 22375129
TI  - Effects of electroconvulsive therapy and repetitive transcranial magnetic
      stimulation on serum brain-derived neurotrophic factor levels in patients with
      depression.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) levels are decreased in
      individuals with depression and increase following antidepressant treatment. The
      objective of this study is to compare pre- and post-treatment serum BDNF levels
      in patients with drug-resistant major depressive disorder (MDD) who received
      either electroconvulsive therapy (ECT) or repetitive transcranial magnetic
      stimulation (rTMS). It is hypothesized that non-pharmacological treatments also
      increase serum BDNF levels. METHODS: This was a prospective, single-blind study
      comparing pre- and post-treatment serum BDNF levels of 29 patients with drug
      resistant MDD who received ECT or rTMS treatment. Serum BDNF levels were measured
      1 week prior to and 1 week after treatment using the sandwich ELISA technique.
      Depression severity was measured 1 week before and 1 week after treatment using
      the Hamilton Depression Rating Scale. Two-sided normal distribution paired t-test
      analysis was used to compare pre- and post-treatment BDNF concentration and
      illness severity. Bivariate correlations using Pearson's coefficient assessed the
      relationship between post-treatment BDNF levels and post-treatment depression
      severity. RESULTS: There was no significant difference in serum BDNF levels
      before and after ECT, although concentrations tended to increase from a baseline
      mean of 9.95-12.29 ng/ml after treatment (p = 0.137). Treatment with rTMS did not
      significantly alter BDNF concentrations (p = 0.282). Depression severity
      significantly decreased following both ECT (p = 0.003) and rTMS (p < 0.001). Post
      treatment BDNF concentration was not significantly correlated with post-treatment
      depression severity in patients who received either ECT (r = -0.133, p = 0.697)
      or rTMS (r = 0.374, p = 0.126). It is important to note that these results are
      based on the small number of patients included in this study. CONCLUSION: This
      study suggests that ECT and rTMS may not exert their clinical effects by altering
      serum BDNF levels in patients with drug-resistant MDD. Serum BDNF concentration
      may not be a biomarker of ECT or rTMS treatment response.

PMID- 22375130
TI  - Explicit learning of arbitrary and non-arbitrary action-effect relations in
      adults and 4-year-olds.
AB  - Ideomotor theories claim that carrying out a movement that produces a perceivable
      effect creates a bidirectional association between the two, which can then be
      used by action control processes to retrieve the associated action by
      anticipating its outcome. Previous implicit-learning studies have shown that
      practice renders novel but action-contingent stimuli effective retrieval cues of
      the action they used to follow, suggesting that experiencing sequences of actions
      and effects creates bidirectional action-effect associations. We investigated
      whether action-effect associations are also acquired under explicit learning
      conditions and whether familiar action-effect relations (such as between a
      trumpet and a trumpet sound) are learned the same way as novel, arbitrary
      relations are. We also investigated whether these factors affect adults and 4
      year-old children equally. Findings suggest that explicit learning produces the
      same bidirectional action-effect associations as implicit-learning does, that non
      arbitrary relations improve performance without affecting learning per se, and
      that adults and young children show equivalent performance - apart from the
      common observation that children have greater difficulty to withstand stimulus
      induced action tendencies.

PMID- 22375131
TI  - Physiological plausibility and boundary conditions of theories of risk
      sensitivity.

PMID- 22375132
TI  - Fast Mapping Across Time: Memory Processes Support Children's Retention of
      Learned Words.
AB  - Children's remarkable ability to map linguistic labels to referents in the world
      is commonly called fast mapping. The current study examined children's (N = 216)
      and adults' (N = 54) retention of fast-mapped words over time (immediately, after
      a 1-week delay, and after a 1-month delay). The fast mapping literature often
      characterizes children's retention of words as consistently high across
      timescales. However, the current study demonstrates that learners forget word
      mappings at a rapid rate. Moreover, these patterns of forgetting parallel
      forgetting functions of domain-general memory processes. Memory processes are
      critical to children's word learning and the role of one such process,
      forgetting, is discussed in detail - forgetting supports extended mapping by
      promoting the memory and generalization of words and categories.

PMID- 22375133
TI  - The role of risk aversion in non-conscious decision making.
AB  - To what extent can people choose advantageously without knowing why they are
      making those choices? This hotly debated question has capitalized on the Iowa
      Gambling Task (IGT), in which people often learn to choose advantageously without
      appearing to know why. However, because the IGT is unconstrained in many
      respects, this finding remains debated and other interpretations are possible
      (e.g., risk aversion, ambiguity aversion, limits of working memory, or
      insensitivity to reward/punishment can explain the finding of the IGT). Here we
      devised an improved variant of the IGT in which the deck-payoff contingency
      switches after subjects repeatedly choose from a good deck, offering the
      statistical power of repeated within-subject measures based on learning the
      reward contingencies associated with each deck. We found that participants
      exhibited low confidence in their choices, as probed with post-decision wagering,
      despite high accuracy in selecting advantageous decks in the task, which is
      putative evidence for non-conscious decision making. However, such a behavioral
      dissociation could also be explained by risk aversion, a tendency to avoid risky
      decisions under uncertainty. By explicitly measuring risk aversion for each
      individual, we predicted subjects' post-decision wagering using Bayesian
      modeling. We found that risk aversion indeed does play a role, but that it did
      not explain the entire effect. Moreover, independently measured risk aversion was
      uncorrelated with risk aversion exhibited during our version of the IGT, raising
      the possibility that the latter risk aversion may be non-conscious. Our findings
      support the idea that people can make optimal choices without being fully aware
      of the basis of their decision. We suggest that non-conscious decision making may
      be mediated by emotional feelings of risk that are based on mechanisms distinct
      from those that support cognitive assessment of risk.

PMID- 22375134
TI  - A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for
      Inducing Blast Injury to in vitro Models.
AB  - Due to the prominent role of improvised explosive devices (IEDs) in wounding
      patterns of U.S. war-fighters in Iraq and Afghanistan, blast injury has risen to
      a new level of importance and is recognized to be a major cause of injuries to
      the brain. However, an injury risk-function for microscopic, macroscopic,
      behavioral, and neurological deficits has yet to be defined. While operational
      blast injuries can be very complex and thus difficult to analyze, a simplified
      blast injury model would facilitate studies correlating biological outcomes with
      blast biomechanics to define tolerance criteria. Blast-induced traumatic brain
      injury (bTBI) results from the translation of a shock wave in-air, such as that
      produced by an IED, into a pressure wave within the skull-brain complex. Our
      blast injury methodology recapitulates this phenomenon in vitro, allowing for
      control of the injury biomechanics via a compressed-gas shock tube used in
      conjunction with a custom-designed, fluid-filled receiver that contains the
      living culture. The receiver converts the air shock wave into a fast-rising
      pressure transient with minimal reflections, mimicking the intracranial pressure
      history in blast. We have developed an organotypic hippocampal slice culture
      model that exhibits cell death when exposed to a 530 +/- 17.7-kPa peak
      overpressure with a 1.026 +/- 0.017-ms duration and 190 +/- 10.7 kPa-ms impulse
      in-air. We have also injured a simplified in vitro model of the blood-brain
      barrier, which exhibits disrupted integrity immediately following exposure to 581
      +/- 10.0 kPa peak overpressure with a 1.067 +/- 0.006-ms duration and 222 +/- 6.9
      kPa-ms impulse in-air. To better prevent and treat bTBI, both the initiating
      biomechanics and the ensuing pathobiology must be understood in greater detail. A
      well-characterized, in vitro model of bTBI, in conjunction with animal models,
      will be a powerful tool for developing strategies to mitigate the risks of bTBI.

PMID- 22375136
TI  - Traumatic injuries in the nervous system.

PMID- 22375135
TI  - Factors that Differentially Affect Daytime and Nighttime Sleep in Drosophila
      melanogaster.
AB  - Rest in the fruit fly Drosophila melanogaster has key characteristics of
      mammalian sleep and is thus considered as a fly version of sleep. Drosophila
      sleep has been studied extensively, with the aim of gaining fundamental insights
      into the evolutionarily conserved functions of sleep as well as the mechanisms
      that regulate it. An interesting question that has not yet been addressed is
      whether fly sleep can be classified into distinct sleep types, each having
      particular biological roles - like rapid eye movement (REM) and non-REM sleep in
      birds and mammals. Typically, Drosophila sleep displays a bimodal pattern,
      consisting of distinct daytime and nighttime components. Notably, daytime and
      nighttime sleep differ with respect to several qualities, such as sleep-bout
      lengths and arousal thresholds. In this short review, we describe several genetic
      and environmental factors that differentially affect daytime and nighttime sleep,
      highlighting the observations suggesting the notion that these temporally
      distinct components of Drosophila sleep may have unique biological functions and
      be regulated by different homeostatic regulatory mechanisms.

PMID- 22375137
TI  - Environmental controls on nitrogen and sulfur cycles in surficial aquatic
      sediments.
AB  - Enhanced anthropogenic inputs of nitrogen (N) and sulfur (S) have disturbed their
      biogeochemical cycling in aquatic and terrestrial ecosystems. The N and S cycles
      interact with one another through competition for labile forms of organic carbon
      between nitrate-reducing and sulfate-reducing bacteria. Furthermore, the N and S
      cycles could interact through nitrate [Formula: see text] reduction coupled to S
      oxidation, consuming [Formula: see text] and producing sulfate [Formula: see
      text] The research questions of this study were: (1) what are the environmental
      factors explaining variability in N and S biogeochemical reaction rates in a wide
      range of surficial aquatic sediments when [Formula: see text] and [Formula: see
      text] are present separately or simultaneously, (2) how the N and S cycles could
      interact through S oxidation coupled to [Formula: see text] reduction, and (3)
      what is the extent of sulfate reduction inhibition by nitrate, and vice versa.
      The N and S biogeochemical reaction rates were measured on intact surface
      sediment slices using flow-through reactors. The two terminal electron acceptors
      [Formula: see text] and [Formula: see text] were added either separately or
      simultaneously and [Formula: see text] and [Formula: see text] reduction rates as
      well as [Formula: see text] reduction linked to S oxidation were determined. We
      used redundancy analysis, to assess how environmental variables were related to
      these rates. Our analysis showed that overlying water pH and salinity were two
      dominant environmental factors that explain 58% of the variance in the N and S
      biogeochemical reaction rates when [Formula: see text] and [Formula: see text]
      were both present. When [Formula: see text] and [Formula: see text] were added
      separately, however, sediment N content in addition to pH and salinity accounted
      for 62% of total variance of the biogeochemical reaction rates. The [Formula: see
      text] addition had little effect on [Formula: see text] reduction; neither did
      the [Formula: see text] addition inhibit [Formula: see text] reduction. The
      presence of [Formula: see text] led to [Formula: see text] production most likely
      due to the oxidation of sulfur. Our observations suggest that metal-bound S,
      instead of free sulfide produced by [Formula: see text] reduction, was
      responsible for the S oxidation.

PMID- 22375138
TI  - Identification and antimicrobial resistance of campylobacter species isolated
      from animal sources.
AB  - BACKGROUND: Campylobacter spp. are together with Salmonella spp. the leading
      causes of human bacterial gastroenteritis worldwide. The most commonly isolated
      species in humans are Campylobacter jejuni and C. coli. The isolation,
      identification, and antimicrobial resistance of Campylobacter spp. from poultry
      and raw meat from slaughterhouses, has been investigated for the first time in
      Greece. During the period from August 2005 to November 2008 a total of 1080
      samples were collected: (a) 830 fecal samples from five poultry farms, (b) 150
      cecal samples from chicken carcasses in a slaughterhouse, and (c) 100 fecal
      samples from one pig farm near the region of Attica. The identification of the
      isolates was performed with conventional (sodium hippurate hydrolysis and
      commercial identification system (Api CAMPY system, bioMerieux, France), as well
      as with and molecular methods based on 16S rRNA species specific gene
      amplification by PCR and subsequent sequence analysis of the PCR products.
      RESULTS: Sixteen Campylobacter strains were isolated, all collected from the
      poultry farms. None of the strains was identified as C. jejuni. Antimicrobial
      susceptibility to six antimicrobials was performed and all the strains were
      susceptible to ciprofloxacin, amoxicillin-clavulanic acid, and gentamicin.
      Thirteen out of 14 C. coli were resistant to erythromycin and all C. coli strains
      were resistant to ampicillin. CONCLUSION: Our results emphasize the need for a
      surveillance and monitoring system with respect to the prevalence and
      antimicrobial resistance of Campylobacter in poultry, as well as for the use of
      antimicrobials in veterinary medicine in Greece.

PMID- 22375139
TI  - Spatial patterns of iron- and methane-oxidizing bacterial communities in an
      irregularly flooded, riparian wetland.
AB  - Iron- and methane-cycling are important processes in wetlands with one connected
      to plant growth and the other to greenhouse gas emission, respectively. In
      contrast to acidic habitats, there is scarce information on the ecology of
      microbes oxidizing ferrous iron at circumneutral pH. The latter is mainly due to
      the lack of isolated representatives and molecular detection techniques.
      Recently, we developed PCR-DGGE and qPCR assays to detect and enumerate
      Gallionella-related neutrophilic iron-oxidizers (Ga-FeOB) enabling the assessment
      of controlling physical as well as biological factors in various ecosystems. In
      this study, we investigated the spatial distribution of Ga-FeOB in co-occurrence
      with methane-oxidizing bacteria (MOB) in a riparian wetland. Soil samples were
      collected at different spatial scales (ranging from meters to centimeters)
      representing a hydrological gradient. The diversity of Ga-FeOB was assessed using
      PCR-DGGE and the abundance of both Ga-FeOB and MOB by qPCR. Geostatistical
      methods were applied to visualize the spatial distribution of both groups.
      Spatial distribution as well as abundance of Ga-FeOB and MOB was clearly
      correlated to the hydrological gradient as expressed in moisture content of the
      soil. Ga-FeOB outnumbered the MOB subgroups suggesting their competitiveness or
      the prevalence of Fe(2+) over CH(4) oxidation in this floodplain.

PMID- 22375140
TI  - The Ubiquitin System and Kaposi's Sarcoma-Associated Herpesvirus.
AB  - Ubiquitination is a post-translational modification in which one or more
      ubiquitin molecules are covalently linked to lysine residues of target proteins.
      The ubiquitin system plays a key role in the regulation of protein degradation,
      which contributes to cell signaling, vesicular trafficking, apoptosis, and immune
      regulation. Bacterial and viral pathogens exploit the cellular ubiquitin system
      by encoding their own proteins to serve their survival and replication in
      infected cells. Recent studies have revealed that Kaposi's sarcoma-associated
      herpesvirus (KSHV) manipulates the ubiquitin system of infected cells to
      facilitate cell proliferation, anti-apoptosis, and evasion from immunity. This
      review summarizes recent developments in our understanding of the molecular
      mechanisms used by KSHV to interact with the cellular ubiquitin machinery.

PMID- 22375141
TI  - Mouse Hepatitis Virus Receptor as a Determinant of the Mouse Susceptibility to
      MHV Infection.
AB  - In this review, we report that the receptor of mouse hepatitis virus (MHV),
      carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is an
      important determinant of mouse susceptibility to MHV infection. This finding was
      revealed by using mouse strains with two different allelic forms of the MHV
      receptor, Ceacam1a and Ceacam1b. Although previous studies indicated that
      susceptibility is determined by a single gene, Ceacam1, our recent work in gene
      replaced mice with chimeric Ceacam1 pointed toward the involvement of other host
      factors (genes) in the susceptibility. Studies on mouse susceptibility to MHV, as
      well as the factors involved in their susceptibility, are overviewed.

PMID- 22375142
TI  - Murine hyperglycemic vasculopathy and cardiomyopathy: whole-genome gene
      expression analysis predicts cellular targets and regulatory networks influenced
      by mannose binding lectin.
AB  - Hyperglycemia, in the absence of type 1 or 2 diabetes, is an independent risk
      factor for cardiovascular disease. We have previously demonstrated a central role
      for mannose binding lectin (MBL)-mediated cardiac dysfunction in acute
      hyperglycemic mice. In this study, we applied whole-genome microarray data
      analysis to investigate MBL's role in systematic gene expression changes. The
      data predict possible intracellular events taking place in multiple cellular
      compartments such as enhanced insulin signaling pathway sensitivity, promoted
      mitochondrial respiratory function, improved cellular energy expenditure and
      protein quality control, improved cytoskeleton structure, and facilitated
      intracellular trafficking, all of which may contribute to the organismal health
      of MBL null mice against acute hyperglycemia. Our data show a tight association
      between gene expression profile and tissue function which might be a very useful
      tool in predicting cellular targets and regulatory networks connected with in
      vivo observations, providing clues for further mechanistic studies.

PMID- 22375144
TI  - Methods for Determining the Statistical Significance of Enrichment or Depletion
      of Gene Ontology Classifications under Weighted Membership.
AB  - High-throughput molecular biology studies, such as microarray assays of gene
      expression, two-hybrid experiments for detecting protein interactions, or ChIP
      Seq experiments for transcription factor binding, often result in an
      "interesting" set of genes - say, genes that are co-expressed or bound by the
      same factor. One way of understanding the biological meaning of such a set is to
      consider what processes or functions, as defined in an ontology, are over
      represented (enriched) or under-represented (depleted) among genes in the set.
      Usually, the significance of enrichment or depletion scores is based on simple
      statistical models and on the membership of genes in different classifications.
      We consider the more general problem of computing p-values for arbitrary integer
      additive statistics, or weighted membership functions. Such membership functions
      can be used to represent, for example, prior knowledge on the role of certain
      genes or classifications, differential importance of different classifications or
      genes to the experimenter, hierarchical relationships between classifications, or
      different degrees of interestingness or evidence for specific genes. We describe
      a generic dynamic programming algorithm that can compute exact p-values for
      arbitrary integer additive statistics. We also describe several optimizations for
      important special cases, which can provide orders-of-magnitude speed up in the
      computations. We apply our methods to datasets describing oxidative
      phosphorylation and parturition and compare p-values based on computations of
      several different statistics for measuring enrichment. We find major differences
      between p-values resulting from these statistics, and that some statistics
      recover "gold standard" annotations of the data better than others. Our work
      establishes a theoretical and algorithmic basis for far richer notions of
      enrichment or depletion of gene sets with respect to gene ontologies than has
      previously been available.

PMID- 22375143
TI  - Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain
      Gene Expression Studies with Semi-Degraded Samples.
AB  - Available statistical preprocessing or quality control analysis tools for gene
      expression microarray datasets are known to greatly affect downstream data
      analysis, especially when degraded samples, unique tissue samples, or novel
      expression assays are used. It is therefore important to assess the validity and
      impact of the assumptions built in to preprocessing schemes for a dataset. We
      developed and assessed a data preprocessing strategy for use with the Illumina
      DASL-based gene expression assay with partially degraded postmortem prefrontal
      cortex samples. The samples were obtained from individuals with autism as part of
      an investigation of the pathogenic factors contributing to autism. Using
      statistical analysis methods and metrics such as those associated with
      multivariate distance matrix regression and mean inter-array correlation, we
      developed a DASL-based assay gene expression preprocessing pipeline to
      accommodate and detect problems with microarray-based gene expression values
      obtained with degraded brain samples. Key steps in the pipeline included outlier
      exclusion, data transformation and normalization, and batch effect and covariate
      corrections. Our goal was to produce a clean dataset for subsequent downstream
      differential expression analysis. We ultimately settled on available
      transformation and normalization algorithms in the R/Bioconductor package lumi
      based on an assessment of their use in various combinations. A log2-transformed,
      quantile-normalized, and batch and seizure-corrected procedure was likely the
      most appropriate for our data. We empirically tested different components of our
      proposed preprocessing strategy and believe that our results suggest that a
      preprocessing strategy that effectively identifies outliers, normalizes the data,
      and corrects for batch effects can be applied to all studies, even those pursued
      with degraded samples.

PMID- 22375146
TI  - A Weighted-Least-Squares Estimation Approach to Comparing Trends in Age-Adjusted
      Cancer Rates Across Overlapping Regions.
AB  - Li and Tiwari (2008) recently developed a corrected Z-test statistic for
      comparing the trends in cancer age-adjusted mortality and incidence rates across
      overlapping geographic regions, by properly adjusting for the correlation between
      the slopes of the fitted simple linear regression equations. One of their key
      assumptions is that the error variances have unknown but common variance.
      However, since the age-adjusted rates are linear combinations of mortality or
      incidence counts, arising naturally from an underlying Poisson process, this
      constant variance assumption may be violated. This paper develops a weighted
      least-squares based test that incorporates heteroscedastic error variances, and
      thus significantly extends the work of Li and Tiwari. The proposed test generally
      outperforms the aforementioned test through simulations and through application
      to the age-adjusted mortality data from the Surveillance, Epidemiology, and End
      Results (SEER) Program of the National Cancer Institute.

PMID- 22375145
TI  - Emerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders.
AB  - The recent discovery of thousands of long non-coding (lnc)RNAs in the human
      genome has prompted investigation of the potential roles of these molecules in
      human biology and medicine. Indeed, it is now well documented that many lncRNAs
      are involved in key biological processes, including dosage compensation, genomic
      imprinting, chromatin regulation, alternative splicing of pre-mRNA, nuclear
      organization; and potentially many other biological processes, which are yet to
      be elucidated. Recently, a number of studies have also reported that lncRNAs are
      dysregulated in a number of human diseases, including several cancers and
      neurological disorders. Although many of these studies have fallen short of
      implicating lncRNAs as causative, they suggest potential roles that warrant
      further in depth investigations. In this review, we discuss the current state of
      knowledge regarding the roles of lncRNAs in cancer and neurological disorders,
      and suggest potential future directions in this rapidly emerging field.

PMID- 22375148
TI  - Mycoplasma pneumoniae pneumonia in children.
AB  - Mycoplasma pneumoniae (MP), the smallest self-replicating biological system, is a
      common cause of upper and lower respiratory tract infections, leading to a wide
      range of pulmonary and extra-pulmonary manifestations. MP pneumonia has been
      reported in 10 to 40% of cases of community-acquired pneumonia and shows an even
      higher proportion during epidemics. MP infection is endemic in larger communities
      of the world with cyclic epidemics every 3 to 7 years. In Korea, 3 to 4-year
      cycles have been observed from the mid-1980s to present. Although a variety of
      serologic assays and polymerase chain reaction (PCR) techniques are available for
      the diagnosis of MP infections, early diagnosis of MP pneumonia is limited by the
      lack of immunoglobulin (Ig) M antibodies and variable PCR results in the early
      stages of the infection. Thus, short-term paired IgM serologic tests may be
      mandatory for an early and definitive diagnosis. MP infection is usually a mild
      and self-limiting disease without specific treatment, and if needed, macrolides
      are generally used as a first-choice drug for children. Recently, macrolide
      resistant MP strains have been reported worldwide. However, there are few reports
      of apparent treatment failure, such as progression of pneumonia to acute
      respiratory distress syndrome despite macrolide treatment. The immunopathogenesis
      of MP pneumonia is believed to be a hyperimmune reaction of the host to the
      insults from MP infection, including cytokine overproduction and immune cell
      activation (T cells). In this context, immunomodulatory treatment
      (corticosteroids or/and intravenous Ig), in addition to antibiotic treatment,
      might be considered for patients with severe infection.

PMID- 22375147
TI  - Environmental tobacco smoke and children's health.
AB  - Passive exposure to tobacco smoke significantly contributes to morbidity and
      mortality in children. Children, in particular, seem to be the most susceptible
      population to the harmful effects of environmental tobacco smoke (ETS). Paternal
      smoking inside the home leads to significant maternal and fetal exposure to ETS
      and may subsequently affect fetal health. ETS has been associated with adverse
      effects on pediatric health, including preterm birth, intrauterine growth
      retardation, perinatal mortality, respiratory illness, neurobehavioral problems,
      and decreased performance in school. A valid estimation of the risks associated
      with tobacco exposure depends on accurate measurement. Nicotine and its major
      metabolite, cotinine, are commonly used as smoking biomarkers, and their levels
      can be determined in various biological specimens such as blood, saliva, and
      urine. Recently, hair analysis was found to be a convenient, noninvasive
      technique for detecting the presence of nicotine exposure. Because
      nicotine/cotinine accumulates in hair during hair growth, it is a unique measure
      of long-term, cumulative exposure to tobacco smoke. Although smoking ban policies
      result in considerable reductions in ETS exposure, children are still exposed
      significantly to tobacco smoke not only in their homes but also in schools,
      restaurants, child-care settings, cars, buses, and other public places.
      Therefore, more effective strategies and public policies to protect preschool
      children from ETS should be consolidated.

PMID- 22375149
TI  - Clinical and genetic characteristics of Gaucher disease according to phenotypic
      subgroups.
AB  - PURPOSE: Gaucher disease is caused by a beta-glucocerebrosidase (GBA) deficiency.
      The aim of this study is to investigate the clinical and genetic characteristics
      according to subtypes of Gaucher disease in the Korean population. METHODS:
      Clinical findings at diagnosis, GBA mutations, and clinical courses were reviewed
      in 20 patients diagnosed with Gaucher disease. RESULTS: Eleven patients were
      diagnosed with non-neuronopathic type, 2 with acute neuronopathic type, and 7
      with chronic neuronopathic type. Most patients presented with hepatosplenomegaly,
      thrombocytopenia, and short stature. In the neuronopathic group, variable
      neurological features, such as seizure, tremor, gaze palsy, and hypotonia, were
      noted at age 8.7+/-4.3 years. B cell lymphoma, protein-losing enteropathy, and
      hydrops fetalis were the atypical manifestations. Biomarkers, including
      chitotriosidase, acid phosphatase, and angiotensin-converting enzyme, increased
      at the initial evaluation and subsequently decreased with enzyme replacement
      treatment (ERT). The clinical findings, including hepatosplenomegaly,
      thrombocytopenia, and skeletal findings, improved following ERT, except for the
      neurological manifestations. L444P was the most common mutation in our cohort.
      One novel mutation, R277C, was found. CONCLUSION: Although the clinical outcome
      for Gaucher disease improved remarkably following ERT, the outcome differed
      according to subtype. Considering the high proportion of the neuronopathic form
      in the Korean population, new therapeutic strategies targeting the central
      nervous system are needed, with the development of a new scoring system and
      biomarkers representing clinical courses in a more comprehensive manner.

PMID- 22375150
TI  - Evaluation of kidney size in children: a pilot study of renal length as a
      surrogate of organ growth.
AB  - PURPOSE: Somatic growth is an important indicator of health in children. Adequate
      organ growth is essential in growth and directly related to body growth. We
      consider renal length as a surrogate of organ growth in growing children.
      Measurement of weight, height, and many anthropometric indices, such as body
      surface area (BSA), body mass index (BMI), and Rohrer and Kaup indices, are used
      to evaluate growth status. The aim of this study was to evaluate the association
      between renal length and somatic parameters and analyze the affecting factors for
      renal size during growth. METHODS: The data for renal length in 66 children (age,
      12.9+/-15.6 months; male/female, 34/32) were obtained. Each kidney was measured
      with ultrasonography and dimercaptosuccinic acid scan. The data on age, sex,
      height, and weight were obtained from the medical records. BSA, BMI, and Rohrer
      and Kaup indices were calculated from measured height and weight. BSA was
      calculated by 2 methods, and is expressed as BSA I and BSA II. RESULTS: There
      were significant correlations between renal size and age, weight, height, BSA I,
      BSA II, and Rohrer index. In the regression analysis, the most significant
      contributing factor to renal growth was height (R(2)=0.636, P<0.001). CONCLUSION:
      Height seems to be the most important factor associated with organ growth in
      growing children. Further studies to evaluate adequate organ growth should be
      carried out.

PMID- 22375151
TI  - Transient carnitine transport defect with cholestatic jaundice: report of one
      case in a premature baby.
AB  - Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) is involved in the
      transport of long-chain fatty acids into the mitochondrial matrix and the removal
      of potentially toxic acylcarnitine esters. Transient carnitine transport defect
      is a rare condition in newborns reported in 1/90,000 live births. In this paper,
      we describe a case of transient carnitine transport defect found in a premature
      baby who had prolonged cholestatic jaundice and poor weight gain, and who
      responded dramatically to oral carnitine supplementation.

PMID- 22375152
TI  - Signal change in hippocampus and current source of spikes in Panayiotopoulos
      syndrome.
AB  - A 4-year-old girl with Panayiotopoulos syndrome presented with a history of 4
      prolonged autonomic seizures. The clinical features of her seizures included, in
      order of occurrence, blank staring, pallor, vomiting, hemi-clonic movement on the
      right side, and unresponsiveness. A brain magnetic resonance imaging (MRI) showed
      a slightly high T(2) signal in the left hippocampus. Interictal
      electoencephalogram revealed spikes in the occipital area of the left hemisphere.
      We analyzed the current-source distribution of the spikes to examine the
      relationship between the current source and the high T(2) signal. The current
      source of the occipital spikes was not only distributed in the occipital area of
      both cerebral hemispheres, but also extended to the posterior temporal area of
      the left hemisphere. These findings suggest that the left temporal lobe may be
      one of the hyperexcitable areas and form part of the epileptogenic area in this
      patient. We hypothesized that the high T(2) signal in the left hippocampus of our
      patient may not have been an incidental lesion, but instead may be related to the
      underlying electroclinical diagnosis of Panayiotopoulos syndrome, and
      particularly seizure. This notion is important because an abnormal T(2) signal in
      the hippocampus may represent an acute stage of hippocampal injury, although
      there is no previous report of hippocampal pathology in Panayiotopoulos syndrome.
      Therefore, long-term observation and serial follow-up MRIs may be needed to
      confirm the clinical significance of the T(2) signal change in the hippocampus of
      this patient.

PMID- 22375153
TI  - Influence of Red Blood Cells on Nanoparticle Targeted Delivery in
      Microcirculation.
AB  - Multifunctional nanomedicine holds considerable promise as the next generation of
      medicine that allows for targeted therapy with minimal toxicity. Most current
      studies on Nanoparticle (NP) drug delivery consider a Newtonian fluid with
      suspending NPs. However, blood is a complex biological fluid composed of
      deformable cells, proteins, platelets, and plasma. For blood flow in capillaries,
      arterioles and venules, the particulate nature of the blood needs to be
      considered in the delivery process. The existence of the cell-free-layer and NP
      cell interaction will largely influence both the dispersion and binding rates,
      thus impact targeted delivery efficacy. In this paper, a particle-cell hybrid
      model is developed to model NP transport, dispersion, and binding dynamics in
      blood suspension. The motion and deformation of red blood cells is captured
      through the Immersed Finite Element Method. The motion and adhesion of individual
      NPs are tracked through Brownian adhesion dynamics. A mapping algorithm and an
      interaction potential function are introduced to consider the cell-particle
      collision. NP dispersion and binding rates are derived from the developed model
      under various rheology conditions. The influence of red blood cells, vascular
      flow rate, and particle size on NP distribution and delivery efficacy is
      characterized. A non-uniform NP distribution profile with higher particle
      concentration near the vessel wall is observed. Such distribution leads to over
      50% higher particle binding rate compared to the case without RBC considered. The
      tumbling motion of RBCs in the core region of the capillary is found to enhance
      NP dispersion, with dispersion rate increases as shear rate increases. Results
      from this study contribute to the fundamental understanding and knowledge on how
      the particulate nature of blood influences NP delivery, which will provide
      mechanistic insights on the nanomedicine design for targeted drug delivery
      applications.

PMID- 22375154
TI  - Analysis of protease activity using quantum dots and resonance energy transfer.
AB  - This review demonstrates the detection of protease activity based on the energy
      transfer of quantum dots (QDs). By incorporation of varying protease substrates
      into designed QD probes both in fluorescence resonance energy transfer (FRET) and
      bioluminescence resonance energy transfer (BRET) system, proteolytic activity led
      to changes in the energy transfer efficiency. Especially due to the superior
      properties of QDs, it can be served as an excellent probe for a multiplexed and
      high-throughput protease assay with high sensitivity. It is anticipated that the
      QD-based FRET/BRET probes will have a great potential for dissecting the
      fundamental roles of proteases and designing potential protease inhibitors as
      therapeutic drugs in biology and nanomedicine.

PMID- 22375155
TI  - Enzymatic self-assembly of nanostructures for theranostics.
AB  - Self-assembly of small molecules or macromolecules through non-covalent or
      covalent bonds to build up supramolecular nanostructures is a prevalent and
      important process in nature. While most chemists use small molecules to assemble
      nanostructures with physical or chemical perturbations, nature adopts enzymes to
      catalyze the reaction to assemble biological, functional nanostructures with high
      efficiency and specificity. Although enzymatic self-assembly of nanostructures
      has been remained challenging for chemists, there are still a few examples of
      using important enzymes to initiate the self-assembly of nanostructures for
      diagnosis or therapy of certain diseases because down-regulation or
      overexpression of certain enzymes always associates with abnormalities of
      tissues/organs or diseases in living body. Herein, we introduce the concept of
      enzymatic self-assembly and illustrate the design and application of enzyme
      catalyzed or -regulated formation of nanostructures for theranostics.

PMID- 22375156
TI  - Optical imaging of cancer-related proteases using near-infrared fluorescence
      matrix metalloproteinase-sensitive and cathepsin B-sensitive probes.
AB  - Cathepsin B and matrix metalloproteinase (MMP) play key roles in tumor
      progression by controlled degradation of extracellular matrix. Consequently,
      these proteases have been attracted in cancer research, and many imaging probes
      utilizing these proteases have been developed. Our groups developed cathepsin B
      and MMP imaging nanoprobes based on polymer nanoparticle platform. Both cathepsin
      B and MMP imaging probes used near-infrared fluorescence (NIRF) dye and dark
      quencher to for high sensitivity, and protease-sensitive peptide sequence in each
      probe authorized high specificity of the probes. We compared the bioactivities of
      cathepsin B and MMP sensitive probes in cancer-related environments to
      investigate the biological property of the probes. As a result, cathepsin B probe
      showed fluorescence recovery after the probe entered the cytoplasm. This property
      could be useful to evaluate the cytoplasmic targeted delivery by using probe
      conjugated nanoparticles in vivo. On the other hand, MMP probe was superior in
      specificity in vivo and tissue study. This comparative study will provide precise
      information about peptide-based optical probes, and allow their proper
      application to cancer diagnosis.

PMID- 22375157
TI  - Photosensitizer-conjugated gold nanorods for enzyme-activatable fluorescence
      imaging and photodynamic therapy.
AB  - We report on the development of photosensitizer-conjugated gold nanorods (MMP2P
      GNR) in which photosensitizers were conjugated onto the surface of gold nanorods
      (GNR) via a protease-cleavable peptide linker. We hypothesized that fluorescence
      and phototoxicity of the conjugated photosensitizers would be suppressed in their
      native state, becoming activated only after cleavage by the target protease
      matrix metalloprotease-2 (MMP2). Quantitative analysis of the fluorescence and
      singlet oxygen generation (SOG) demonstrated that the MMP2P-GNR conjugate emitted
      fluorescence intensity corresponding to 0.4% +/- 0.01% and an SOG efficiency of
      0.89% +/- 1.04% compared to free pyropheophorbide-a. From the in vitro cell
      studies using HT1080 cells that overexpress MMP2 and BT20 cells that lack MMP2,
      we observed that fluorescence and SOG was mediated by the presence or absence of
      MMP2 in these cell lines. This novel activatable photosensitizing system may be
      useful for protease-mediated fluorescence imaging and subsequent photodynamic
      therapy for various cancers.

PMID- 22375158
TI  - Measurement of MMP Activity in Synovial Fluid in Cases of Osteoarthritis and
      Acute Inflammatory Conditions of the Knee Joints Using a Fluorogenic Peptide
      Probe-Immobilized Diagnostic Kit.
AB  - PURPOSE: A fluorogenic peptide probe-immobilized diagnostic kit was used to
      analyze MMP activity in the synovial fluids (SFs) from patients with
      osteoarthritis (OA) and acute inflammatory conditions of the knee joint. METHODS:
      The MMP diagnostic kit containing a polymer-conjugated MMP probe immobilized on a
      96-well plate was utilized for high-throughput screening of MMP activity in SFs
      from OA patients (n = 33) and patients with acute inflammatory conditions of the
      knee joint (n = 5). RESULTS: Compared to SF from OA patients, SF from patients
      with acute inflammatory conditions of the knee joint presented stronger NIR
      fluorescent signals. In gelatin zymography, most samples from patients with acute
      inflammatory conditions of the knee joint also displayed 92 kDa (pro-form) MMP-9
      and faint 84 kDa (active form) MMP-9, while SF from OA patients did not display
      detectable MMP-9 activity . CONCLUSION: The presence of a strong fluorescence
      signal from the MMP diagnostic kit corresponded well with patients with acute
      inflammatory conditions of the knee joint. The results suggest that our MMP
      diagnostic kit can be useful in differentiation between early stages of OA and
      acute inflammatory conditions of the knee joint.

PMID- 22375159
TI  - In vivo monitoring of liver damage using caspase-3 probe.
AB  - Real-time monitoring of cellular and organ conditions improves our understanding
      of various physiopathological phenomena. Such monitoring is expected to provide
      important alternatives for clinical diagnosis and therapy. We have sought to show
      physiopathological changes of organs as well as cells. Here, we present an
      example of in vivo imaging of liver states using the luciferase-based caspase-3
      optical probe. We examined dynamic changes of apoptosis (caspase-3 activity) of a
      mouse liver as well as those of liver cells, proving that the emitted signals
      reflected the biochemically evaluated apoptotic cell death. In live liver cell
      (AML 12) experiments, the optical probe for caspase-3 activity emitted signals in
      response to Fas-ligand, staurosporine and hypoxia/reoxygenation, demonstrating
      that the probe can measure cellular apoptosis quantitatively. We therefore
      applied this probe for mouse liver ischemia/reperfusion (I/R) and drug-toxicity
      to liver. By expressing the probe in a mouse liver adenovirally, we imaged liver
      caspase-3 activity (i.e. apoptotic damage) non-invasively and chronologically in
      the hepatic I/R model of mice. The duration of liver ischemia affected the post
      ischemic caspase-dependent damage. Ischemia (up to 60 min) enhanced liver damage
      after reperfusion, but prolonged ischemia (90 min of ischemia) induced not
      apoptotic cell death but necrotic cell death. Direct observations of the changes
      of organ conditions elucidated the dynamism of organ function and damage. These
      technologies clearly possess clinical relevance. They are expected to provide a
      new diagnostic tool for various clinical settings in the future.

PMID- 22375160
TI  - FLIM-FRET Imaging of Caspase-3 Activity in Live Cells Using Pair of Red
      Fluorescent Proteins.
AB  - We report a new technique to detect enzyme activity inside cells. The method
      based on Fluorescence Lifetime Imaging (FLIM) technology allows one to follow
      sensor cleavage by proteolytic enzyme caspase-3. Specifically, we use the FLIM
      FRET of living cells via the confocal fluorescence microscopy. A specially
      designed lentivector pLVT with the DNA fragment of TagRFP-23-KFP was applied for
      transduction of A549 cell lines. Computer simulations are carried out to estimate
      FRET efficiency and to analyze possible steric restrictions of the reaction
      between the substrate TagRFP-23-KFP and caspase-3 dimer. Successful use of the
      fuse protein TagRFP-23-KFP to register the caspase-3 activation based on average
      life-time measurements is demonstrated. We show that the average life-time
      distribution is dramatically changed for cells with the modified morphology that
      is typical for apoptosis. Namely, the short-lived component at 1.8-2.1 ns
      completely disappears and the long-lived component appears at 2.4-2.6 ns. The
      latter is a fingerprint of the TagRFP molecule released after cleavage of the
      TagRFP-23-KFP complex by caspase-3. Analysis of life-time distributions for
      population of cells allows us to discriminate apoptotic and surviving cells
      within single frame and to peform statistical analysis of drug efficiency. This
      system can be adjusted for HTS by using special readers oriented on measurements
      of fluorescence life-time.

PMID- 22375161
TI  - Coping strategies and immune neglect in affective forecasting: Direct evidence
      and key moderators.
AB  - Affective forecasting skills have important implications for decision making.
      However, recent research suggests that immune neglect - the tendency to overlook
      coping strategies that reduce future distress - may lead to affective forecasting
      problems. Prior evidence for immune neglect has been indirect. More direct
      evidence and a deeper understanding of immune neglect are vital to informing the
      design of future decision-support interventions. In the current study, young
      adults (N = 325) supplied predicted, actual, and recollected reactions to an
      emotionally-evocative interpersonal event, Valentine's Day. Based on
      participants' qualitative descriptions of the holiday, a team of raters reliably
      coded the effectiveness of their coping strategies. Supporting the immune neglect
      hypothesis, participants overlooked the powerful role of coping strategies when
      predicting their emotional reactions. Immune neglect was present not only for
      those experiencing the holiday negatively (non-daters) but also for those
      experiencing it positively (daters), suggesting that the bias may be more robust
      than originally theorized. Immune neglect was greater for immediate emotional
      reactions than more enduring reactions. Further, immune neglect was conspicuously
      absent from recollected emotional reactions. Implications for decision-support
      interventions are discussed.

PMID- 22375162
TI  - BAYESIAN PHASE I/II ADAPTIVELY RANDOMIZED ONCOLOGY TRIALS WITH COMBINED DRUGS.
AB  - We propose a new integrated phase I/II trial design to identify the most
      efficacious dose combination that also satisfies certain safety requirements for
      drug-combination trials. We first take a Bayesian copula-type model for dose
      finding in phase I. After identifying a set of admissible doses, we immediately
      move the entire set forward to phase II. We propose a novel adaptive
      randomization scheme to favor assigning patients to more efficacious dose
      combination arms. Our adaptive randomization scheme takes into account both the
      point estimate and variability of efficacy. By using a moving reference to
      compare the relative efficacy among treatment arms, our method achieves a high
      resolution to distinguish different arms. We also consider groupwise adaptive
      randomization when efficacy is late-onset. We conduct extensive simulation
      studies to examine the operating characteristics of the proposed design, and
      illustrate our method using a phase I/II melanoma clinical trial.

PMID- 22375163
TI  - Diabetes patients and non-diabetic patients intensive care unit and hospital
      mortality risks associated with sepsis.
AB  - AIM: To compare mortality risks associated with known diabetic patients to
      hyperglycemic non-diabetic patients. METHODS: PubMed data base was searched for
      patients with sepsis, bacteremia, mortality and diabetes. Articles that also
      identified new onset hyperglycemia (NOH) (fasting blood glucose > 125 mg/dL or
      random blood glucose > 199 mg/dL) were identified and reviewed. Nine studies were
      evaluated with regards to hyperglycemia and hospital mortality and five of the
      nine were summarized with regards to intensive care unit (ICU) mortality.
      RESULTS: Historically hyperglycemia has been believed to be equally harmful in
      known diabetic patients and non-diabetics patients admitted to the hospital.
      Unexpectedly, having a history of diabetes when admitted to the hospital was
      associated with a reduced risk of hospital mortality. Approximately 17% of
      patients admitted to hospital have NOH and 24% have diabetes mellitus. Hospital
      mortality was significantly increased in all nine studies of patients with NOH as
      compared to known diabetic patients (26.7% +/- 3.4% vs 12.5% +/- 3.4%, P < 0.05;
      analysis of variance). Unadjusted ICU mortality was evaluated in five studies and
      was more than doubled for those patients with NOH as compared to known diabetic
      patients (25.3% +/- 3.3% vs 12.8% +/- 2.6%, P < 0.05) despite having similar
      blood glucose concentrations. Most importantly, having NOH was associated with an
      increased ICU and a 2.7-fold increase in hospital mortality when compared to
      hyperglycemic diabetic patients. The mortality benefit of being diabetic is
      unclear but may have to do with adaptation to hyperglycemia over time. Having a
      history of diabetes mellitus and prior episodes of hyperglycemia may provide time
      for the immune system to adapt to hyperglycemia and result in a reduced mortality
      risk. Understanding why diabetic patients have a lower than expected hospital
      mortality rate even with bacteremia or acute respiratory distress syndrome needs
      further study. CONCLUSION: Having hyperglycemia without a history of previous
      diabetes mellitus is a major independent risk factor for ICU and hospital
      mortality.

PMID- 22375164
TI  - Toddlers' choice: Yo-Yoing diabetes control or deci-unit insulin dosing?
AB  - While the incidence of toddlers' diabetes is soaring, their mainstay insulins
      were withdrawn, namely the weak 10% or 20% insulin mixtures (WIM), which were
      injected only once or twice daily. Consequently, toddlers are coerced to use an
      insulin pump, multi-dose insulin regime (MuDIR), mix or dilute insulins. This
      paper highlights the difficulties and proposes a simple solution. While an
      insulin pump is the best available option, it is not readily available for
      everyone. Mixing insulins is not sufficiently precise in small doses. Although
      diluting insulin would allow precise dosing and reduce the dose variability
      secondary to dribbling after injections, it, like insulin mixing, deprives
      children from using the pen and related child-friendly accessories. In MuDIR, we
      inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM. Thus,
      on using a half unit (1/2unit) insulin pen, a dose of 0.5, 1, 1.5 and 2 units are
      adjusted in steps of 100%, 50%, 33% or 25%; unlike the advisable 5%-20%. This
      does not easily match the tiny erratic meals of grazing toddlers. Maternal
      anxiety peaks on watching yo-yoing glycemia. Carers have to accept either
      persistently high sugar or wild fluctuation. The risks of such poor glycemic
      pattern are increasingly recognized. Using insulin U20 in a 1/2unit disposable
      pen allows deci-unit dosing, with 5%-20% dose-tuning, greater accuracy on
      delivering small doses and reduction of dose variability from dribbling. Deci
      unit dosing may help avoid wide glycemic swings and provide the affordable
      alternative to insulin pumps for toddlers. Deci-unit pen materializes the Human
      Rights of Children, a safer and effective treatment.

PMID- 22375165
TI  - Recent advances in noncardiac chest pain in Korea.
AB  - Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac
      chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western
      countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to
      underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean
      patients suffering from NCCP. Therefore, a careful history of the predominant
      symptoms, including heartburn and acid regurgitation, is relatively indicative of
      the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients
      aged 40 years and over who have been diagnosed with NCCP but who are without
      alarming features should undergo endoscopy to exclude gastric cancer or peptic
      ulcers because of the higher prevalence of peptic ulcer disease and gastric
      cancers in the region. In a primary care setting, in the absence of any alarming
      symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is
      sufficient for the presumptive diagnosis of GERD. In addition, the optimal
      duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less
      frequent or atypical in Korean patients than in patients from Western countries.
      In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2
      months) with double the standard dose of a PPI is required to alleviate symptoms.
      Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer
      significant improvement of chest pain control in non-GERD-related NCCP. Most
      traditionally available tricyclics or heterocyclics have many undesirable
      effects. Therefore, newer drugs with fewer side effects (for example, the
      serotonin - norepinephrine reuptake inhibitors) may be needed.

PMID- 22375166
TI  - Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic
      Targets in Obesity.
AB  - The global obesity epidemic has resulted in significant morbidity and mortality.
      However, the medical treatment of obesity is limited. Gastric bypass is an
      effective surgical treatment but carries significant perioperative risks. The gut
      hormones, peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1),
      are elevated following gastric bypass and have been shown to reduce food intake.
      They may provide new therapeutic targets. This review article provides an
      overview of the central control of food intake and the role of PYY and GLP-1 in
      appetite control. Key translational animal and human studies are reviewed.

PMID- 22375167
TI  - Evolutionary History of the Helicobacter pylori Genome: Implications for Gastric
      Carcinogenesis.
AB  - The genome of the bacterium Helicobacter pylori has evolved over the millennia
      since its migration out of Africa along with its human host approximately 60,000
      years ago. Human migrations, after thousands of years of permanent settlement in
      those lands, resulted in seven prototypes of genetic populations of H. pylori
      with distinct geographical distributions. In all continents, present day isolates
      of H. pylori have molecular markers that reflect population migrations. The
      colonization of the Americas as well as the slave trade introduced European and
      African strains to the New World. The relationship between H. pylori genome and
      gastric cancer rates is linked to the presence of the cagA gene, but the
      knowledge on this subject is incomplete because other genes may be involved in
      certain populations. A new situation for Homo sapiens is the absence of H. pylori
      colonization in certain, mostly affluent, populations, apparently brought about
      by improved home sanitation and widespread use of antibiotics during the last
      decades. The disappearance of H. pylori from the human microbiota may be linked
      to emerging epidemics of esophageal adenocarcinoma, some allergic diseases such
      as asthma and some autoimmune disorders.

PMID- 22375168
TI  - The biology of cancer stem cells and its clinical implication in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment
      options in its advanced state. The molecular mechanisms underlying HCC remain
      unclear because of the complexity of its multi-step development process. Cancer
      stem cells (CSCs) are defined as a small population of cells within a tumor that
      possess the capability for self-renewal and the generation of heterogeneous
      lineages of cancer cells. To date, there have been two theories concerning the
      mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and
      the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been
      established over the past decade, and the roles of CSCs in the carcinogenic
      processes of various cancers, including HCC, have been emphasized. Previous
      experimental and clinical evidence indicated the existence of liver CSCs;
      however, the potential mechanistic links between liver CSCs and the development
      of HCC in humans are not fully understood. Although definitive cell surface
      markers for liver CSCs have not yet been found, several putative markers have
      been identified, which allow the prospective isolation of CSCs from HCC. The
      identification and characterization of CSCs in HCC is essential for a better
      understanding of tumor initiation or progression in relation to signaling
      pathways. These markers could be used along with clinical parameters for the
      prediction of chemoresistance, radioresistance, metastasis and survival and may
      represent potential targets for the development of new molecular therapies
      against HCC. This review describes the current evidence for the existence and
      function of liver CSCs and discuss the clinical implications of CSCs in patients
      demonstrating resistance to conventional anti-cancer therapies, as well as
      clinical outcomes. Such data may provide a future perspective for targeted
      therapy in HCC.

PMID- 22375169
TI  - Efficacy of the Combination of Tetracycline, Amoxicillin, and Lansoprazole in the
      Eradication of Helicobacter pylori in Treatment-Naive Patients and in Patients
      Who Are Not Responsive to Clarithromycin-Based Regimens: A Pilot Study.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the eradication rate of a
      triple therapy regimen that included a proton pump inhibitor, amoxicillin, and
      tetracycline instead of clarithromycin in treatment-Naive patients and in
      patients who did not respond to standard triple therapy. METHODS: This study
      included 110 patients infected with Helicobacter pylori. Patients in groups A and
      B were treatment-Naive, and those in group C were not responsive to previous
      standard triple therapy. Patients in group A (n=40) received lansoprazole 30 mg
      b.i.d., amoxicillin 1,000 mg b.i.d., and clarithromycin 500 mg b.i.d. for 14
      days. Patients in groups B (n=40) and C (n=30) received lansoprazole 30 mg
      b.i.d., amoxicillin 1,000 mg b.i.d., and tetracycline 500 mg q.i.d. for 14 days.
      RESULTS: In group A, eradication was achieved in 18 (45%) of the 40 patients
      included in the intention-to-treat (ITT) analysis and in 18 (47.4%) of the 38
      patients included in the per-protocol (PP) analysis. In group B, eradication was
      achieved in 15 (37.5%) of the 40 patients included in the ITT analysis and in 15
      (39.3%) of the 38 patients included in the PP analysis. In group C, eradication
      was achieved in 14 (46.6%) of the 30 patients included in the ITT analysis and in
      14 (43.8%) of the 29 patients included in the PP analysis. There was no
      statistically significant difference among the 3 groups with regard to
      eradication rates (p>0.05). CONCLUSIONS: Despite the low rate of resistance to
      tetracycline, the combination of lansoprazole, amoxicillin, and tetracycline
      instead of clarithromycin is not a good option for the eradication of H. pylori.

PMID- 22375170
TI  - The Immunohistochemical Expression of STAT3, Bcl-xL, and MMP-2 Proteins in Colon
      Adenoma and Adenocarcinoma.
AB  - BACKGROUND/AIMS: Signal transducers and activators of transcription (STATs) are a
      family of transcription factors that are activated in response to cytokines and
      growth factors. STAT3 activation has been implicated in modulating the activity
      of downstream mediators, such as Bcl-xL and matrix metalloproteinase-2 (MMP-2).
      The aim of this study was to investigate the immunohistochemical expression of
      STAT3, B-cell lymphoma-extra large (Bcl-xL), and MMP-2 proteins according to
      histopathological parameters in colon adenocarcinomas, including lymph node
      metastasis, tumor differentiation, the TNM stage and the tumor size. METHODS:
      Immunohistochemical staining with monoclonal STAT3, Bcl-xL, and MMP-2 antibodies
      was performed on paraffin-embedded specimens from 20 colon adenomas and 39
      adenocarcinomas. RESULTS: The expression of STAT3, Bcl-xL, and MMP-2 was
      increased in the adenocarcinomas as compared with the adenomas (p<0.001). STAT3
      expression was stronger in tumors with a distant metastasis than in tumors
      without a distant metastasis (p=0.012). A larger tumor size was related to an
      increase in STAT3 expression (p=0.035). CONCLUSIONS: STAT3, Bcl-xL, and MMP-2 may
      play important roles in the tumorigenesis of colorectal carcinoma. STAT3 may be
      indicative of a poor prognosis due to its correlation with distant metastases and
      a larger tumor size.

PMID- 22375172
TI  - The feasibility and safety of the endoscopic submucosal dissection of superficial
      gastric neoplastic lesions in patients with compensated liver cirrhosis: a
      retrospective study.
AB  - BACKGROUND/AIMS: When undergoing endoscopic submucosal dissection (ESD), patients
      with liver cirrhosis (LC) may suffer from a high risk of bleeding, bacteremia and
      tissue vulnerability. There have been few reports evaluating the efficacy and
      safety of ESD in patients with LC. METHODS: From January 2004 to March 2010, 23
      patients with LC (cirrhosis group) underwent ESD for superficial gastric
      neoplastic lesions. The number of patients with a liver function in the Child
      Pugh classes A and B were 20 and 3, respectively. The clinical outcomes and
      complications were compared with 69 patients without LC (control group) that were
      matched for age and sex. RESULTS: The en bloc resection, R0 resection and en bloc
      plus R0 resection rates of the cirrhosis group were 82.6%, 91.3%, and 82.6%,
      respectively, and did not show significant differences from the rates of the
      control group. No local recurrence was found in either group during the follow-up
      period. The procedure length of time (41.0 vs 39.0 minutes), rate of bleeding
      (4.3% vs 7.2%) and rate of perforation (0.0% vs 1.4%) in the cirrhosis group were
      also comparable to the results from the control group. CONCLUSIONS: ESD was
      safely performed in patients with LC, and satisfactory outcomes were achieved
      with high en bloc and R0 resection rates for superficial gastric neoplastic
      lesions.

PMID- 22375171
TI  - Glomus tumor of the stomach: a clinicopathologic analysis of 10 cases and review
      of the literature.
AB  - BACKGROUND/AIMS: Gastric glomus tumors are extremely rare, and presurgical
      confirmation is often impossible. The identification of clinical and radiologic
      characteristics of this tumor type is important for preoperative diagnosis and
      treatment planning. METHODS: In this study, we analyzed 10 cases of gastric
      glomus tumors resected at a single institute over 9 years. RESULTS: Eight of the
      patients were men and 2 were women, with a mean age of 49 years. Five patients
      presented with abdominal discomfort or pain, 1 presented with anemia, and the
      remaining 4 cases were found incidentally during endoscopic examinations. The
      most common location of the tumor was the antrum (n=7), followed by the low (n=2)
      and high body (n=1). Although the endoscopic ultrasonography findings were
      variable, contrast-enhanced computed tomography generally showed a strong
      homogeneous enhancement. The resected tumors were well-demarcated solid masses
      with sizes ranging from 1.0 to 3.6 cm. Microscopically, the masses were composed
      of abundant vascular channels with clusters of uniform and round glomus cells.
      There was no evidence of recurrence after complete surgical resection.
      CONCLUSIONS: Gastric glomus tumors are unusual, distinct lesions that should be
      considered in the differential diagnosis of a gastric submucosal mass. Unlike
      their deep soft tissue counterparts, most glomus tumors in the stomach are
      benign.

PMID- 22375173
TI  - The Miss Rate for Colorectal Adenoma Determined by Quality-Adjusted, Back-to-Back
      Colonoscopies.
AB  - BACKGROUND/AIMS: Colonoscopy is considered to be the gold standard for detecting
      adenomatous polyps. Polyps are missed during colonoscopic examination at a rate
      that varies from 6% to 27%. The adenoma miss rate affects colonoscopic
      surveillance intervals and procedural quality. We aimed to assess the adenoma
      miss rate and the variables affecting the rate using same-day, quality-adjusted,
      back-to-back colonoscopies. METHODS: This prospective study was performed at a
      single institution and included 149 patients. Two consecutive same-day
      colonoscopies were performed by two experienced endoscopists. The adenoma miss
      rates and variables affecting the missed adenomas, including polyp
      characteristics and procedure times, were evaluated. RESULTS: The miss rates of
      polyps, adenomas, and advanced adenomas were 16.8%, 17%, and 5.4%, respectively.
      The smaller polyps and increased number of polyps detected during the first
      colonoscopy were more likely to be missed. A longer insertion time during the
      colonoscopy was correlated with an increased adenoma detection rate. CONCLUSIONS:
      There was a significant miss rate in the detection of colonic adenomas even in
      quality-adjusted, back-to-back colonoscopies. The adenoma miss rate can be
      reduced with a sufficient observation time during colonoscopic insertion. The
      development of specific technological methods to reduce the adenoma miss rate is
      necessary.

PMID- 22375174
TI  - The Role of CDX2 in Intestinal Metaplasia Evaluated Using Immunohistochemistry.
AB  - BACKGROUND/AIMS: Intestinal metaplasia (IM) has been regarded as a premalignant
      condition. This study evaluated the role of the transforming factor CDX2
      according to the severity and type of IM. METHODS: This analysis was performed on
      383 subjects with IM in the antrum and/or body, with diagnoses that were
      categorized as controls, dysplasias, and gastric cancers. The IM grades were
      classified into four groups as negative, mild, moderate or severe using the
      updated Sydney scoring system. The IM subtypes were categorized as type I, type
      II, and type III using high iron diamine and alcian blue (pH 2.5) staining. The
      CDX2 expression in the IM foci was evaluated using immunohistochemistry in
      specimens from the antrum and/or body. RESULTS: CDX2 expression increased
      according to IM severity (p=0.001) but was not associated with the IM subtype
      (p=0.881) in the antrum specimens. Similarly, CDX2 expression increased according
      to the IM grade (p=0.001) but was not associated with the IM subtype (p=0.755) in
      the body specimens. CDX2 expression was also increased according to baseline
      disease in the antrum, especially dysplastic and GC group (p=0.003), but not in
      the body (p=0.582). However, status of Helicobacter pylori infection was not
      associated with CDX2 expression in the antrum (p=0.692) and body (p=0.271).
      CONCLUSIONS: These results show that CDX2 expression is associated with the IM
      grade regardless of the IM subtype and that it was more frequent in the dysplasia
      group. These results suggest that CDX2 expression might play an important role in
      the progression of IM in various environments that can affect neoplastic change.

PMID- 22375175
TI  - The clinical factors for predicting severe diverticulitis in Korea: a comparison
      with Western countries.
AB  - BACKGROUND/AIMS: It is unclear whether the risk factors associated with
      complicated diverticulitis in Asian and Western countries are the same. We
      evaluated the risk factors associated with severe diverticulitis (SD) in Korea
      and compared the clinical characteristics of diverticulitis according to
      location. METHODS: A retrospective review of 190 patients hospitalized with acute
      diverticulitis from January 2005 to June 2010 was conducted. SD was defined as
      one of the following: perforation, abscess, obstruction, sepsis, or peritonitis
      that required an urgent operation. RESULTS: Twenty-four patients (12.6%) were
      diagnosed with SD. SD was significantly associated with older age, a fever over
      38C, changes in bowel habits and a high visceral adipose tissue (VAT)/total
      adipose tissue (TAT) ratio. Multivariate analysis showed that the risk factors
      for developing SD were an age of 40 years or more (odds ratio [OR], 3.2;
      p=0.032), male gender (OR, 4.0; p=0.021) and left-sided diverticulitis (OR, 6.2;
      p=0.017). Right-sided diverticulitis (n=175, 92.1%) was significantly associated
      with younger ages, fewer changes in bowel habits, fewer comorbidities and non-SD.
      CONCLUSIONS: This study suggests that the risk factors for developing SD in
      Korea, where right-sided diverticulitis is predominant, are the male gender, an
      age of more than 40 years old, and left-sided diverticulitis. Given that there
      are different risk factors for developing SD in Western countries, different
      strategies for the treatment of diverticulitis in the Korean population seem to
      be needed.

PMID- 22375177
TI  - Ischemia-modified albumin levels in children with chronic liver disease.
AB  - BACKGROUND/AIMS: Ischemia-modified albumin (IMA) levels have been shown to
      correlate with the severity of liver failure in adults. However, the role of IMA
      levels has not been evaluated in children with chronic liver disease (CLD). We
      analyzed the clinical significance of IMA levels in children with CLD. METHODS:
      Thirty-three children with CLD and 33 healthy children were included in the
      study. Blood was collected to analyze biochemical parameters, oxidant status, and
      IMA. Liver biopsies were re-evaluated for liver fibrosis; severe fibrosis (SF)
      was defined as fibrosis stage >=4. RESULTS: THE IMA AND AND IMA TO ALBUMIN RATIOS
      (IMARS) WERE SIGNIFICANTLY HIGHER IN CHILDREN WITH CLD THAN IN THOSE WITHOUT
      (IMA: 0.545+/-0.095 vs 0.481+/-0.062, p=0.003; IMAR: 0.152+/-0.046 vs 0.126+/
      0.018, p=0.04). The IMAR was positively correlated with the pediatric end-stage
      liver disease score (p=0.03, r=0.503) and fibrosis score (p=0.021, r=0.400).
      Patients with SF had higher IMARs compared to patients with mild fibrosis
      (0.181+/-0.056 vs 0.134+/-0.025, p=0.003). The area under the receiver operation
      curve (AUROC) for predicting SF was 0.78 (p=0.006). Using a cutoff ratio value of
      0.140, the sensitivity and specificity were 84% and 70%, respectively. The AUROC
      for predicting the need for liver transplantation and/or death was 0.82
      (p=0.013). With a cutoff value of 0.156, the sensitivity and specificity was 83%
      and 82%, respectively. Kaplan-Meier analysis revealed increased morbidity and/or
      mortality in the group with an IMAR>0.156 (50% vs 4.3%, p=0.005). CONCLUSIONS:
      IMARs have been shown to provide important clues in predicting the fibrosis stage
      of the disease and determining the outcome in children with CLD.

PMID- 22375176
TI  - Persistence of Protective Hepatitis B Surface Antibody Titers after Successful
      Double-Dose Hepatitis B Virus Rescue Vaccination in HIV-Infected Patients.
AB  - BACKGROUND/AIMS: To assess the durability of protective hepatitis B surface
      antibody (anti-HBs) titers in HIV-infected patients who responded to double-dose
      hepatitis B virus (HBV) rescue vaccination. METHODS: A retrospective chart review
      was performed for HIV-infected patients who received the double-dose HBV rescue
      vaccination at 0-, 1-, and 2-month intervals after they had failed conventional
      HBV vaccination series. A protective antibody response was defined as an anti-HBs
      titer >=10 mIU/mL. RESULTS: Of 54 HIV-infected patients who received a double
      dose HBV rescue vaccination, 44 patients (81.5%) had a positive response and
      achieved protective anti-HB titers. Of the 44 patients who developed protective
      anti-HB titers, 33 patients received an evaluation of their anti-HB titers 12
      months later. Of the 33 patients, 19 (57.6%) had persistent protective anti-HB
      titers (persistent responders, PR), and 14 patients (42.4%) lost their protective
      anti-HB titers (nonpersistent responders, NPR). There were significantly more
      patients who had an undetectable HIV viral load (<50 copies/mL) at baseline and
      follow-up in the PR group (11/19, 57.9%) than in the NPR group (3/14, 21.4%,
      p=0.036). Logistic regression analysis showed that an undetectable HIV viral load
      at baseline and follow-up (odds ratio, 12.973; 95% confidence interval, 1.189 to
      141.515; p=0.036) was associated with PR. CONCLUSIONS: Protective anti-HB titers
      may decrease over time after successful double-dose HBV rescue vaccination in HIV
      infected patients. HIV viral load suppression could improve the persistence of
      anti-HB titers.

PMID- 22375178
TI  - Efficacy and tolerability of peginterferon alpha plus ribavirin in the routine
      daily treatment of chronic hepatitis C patients in Korea: a multi-center,
      retrospective observational study.
AB  - BACKGROUND/AIMS: We aimed to evaluate the efficacy and safety of peginterferon
      plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in
      Korea. METHODS: We retrospectively analyzed the medical records of 758 CHC
      patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14
      university hospitals in the Gyeonggi-Incheon area in Korea. RESULTS: Hepatitis C
      virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was
      detected in 35.5%. Baseline HCV RNA level was >=6*10(5) IU/mL in 51.6% of
      patients. The sustained virological response (SVR) rate was 59.6% regardless of
      genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate
      analysis, male gender (p=0.011), early virological response (p<0.001), genotype
      2/3 (p<0.001), HCV RNA <6*10(5) IU/mL (p=0.005) and adherence to the drug >80% of
      the planned dose (p<0.001) were associated with SVR. The rate of premature
      discontinuation was 35.7%. The main reason for withdrawal was intolerance to the
      drug due to common adverse events or cytopenia (48.2%). CONCLUSIONS: Our data
      suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is
      better in Koreans than in Caucasians for the treatment of CHC, corroborating
      previous studies that have shown the superior therapeutic efficacy of this
      regimen in Asians.

PMID- 22375179
TI  - Recurrence of bile duct stones after endoscopic papillary large balloon dilation
      combined with limited sphincterotomy: long-term follow-up study.
AB  - BACKGROUND/AIMS: Endoscopic papillary large-balloon dilation combined with
      limited endoscopic sphincterotomy (EPLBD+ES) is promising for the treatment of
      common bile duct (CBD) stones. The aim of this study was to clarify the
      recurrence rate and the risk factors for CBD stones after EPLBD+ES. METHODS: In
      total, 100 patients who underwent EPLBD+ES from 2006 to 2007 were evaluated
      retrospectively. One hundred and nine patients who were treated with endoscopic
      sphincterotomy (ES) from 2004 to 2005 were set as the historical control group.
      Various risk factors for the recurrence of bile duct stones were analyzed.
      RESULTS: Of the 209 patients, the duration of follow-up was 32.5+/-4.5 months in
      the EPLBD+ES group and 31.8+/-6.0 months in the ES group. The recurrence rate of
      CBD stones was 11.0% (11/100) in the EPLBD+ES group and 13.8% (15/109) in the ES
      group (p=0.546). The cumulative recurrence rate of stones was not significantly
      different between the EPLBD+ES and ES groups (log rank, p=0.537). Univariate
      analysis showed that the diameter of the CBD (>=22 mm) was the only predictive
      variable that could differentiate recurrence from nonrecurrence in the EPLBD+ES
      group. Multivariate analysis revealed that the diameter of the bile duct was the
      only risk factor for stone recurrence (p=0.022; odds ratio, 1.175; 95% confidence
      interval, 1.023 to 1.348). CONCLUSIONS: The recurrence rate of CBD stones after
      EPLBD+ES is comparable to that of the ES group, and a dilated CBD appears to
      increase the risk of bile duct stone recurrence.

PMID- 22375180
TI  - One-Step Transpapillary Balloon Dilation under Cap-Fitted Endoscopy without a
      Preceding Sphincterotomy for the Removal of Bile Duct Stones in Billroth II
      Gastrectomy.
AB  - BACKGROUND/AIMS: Endoscopic sphincterotomy may be limited in Billroth II
      gastrectomy because of difficulty in orientating the duodenoscope and
      sphincterotome as a result of altered anatomy. This study was planned to
      investigate the efficacy and safety of endoscopic transpapillary large balloon
      dilation (EPBD) without preceding sphincterotomy for removal of large CBD stones
      in Billroth II gastrectomy. METHODS: Between March 2010 and February 2011, one
      step EPBD under cap-fitted forward-viewing endoscopy was performed in patients
      who had undergone Billroth II gastrectomy at two tertiary referral centers. Main
      outcome measurements were successful duct clearance and EPBD-related
      complications. RESULTS: Successful access to major duodenal papilla was performed
      in 13 patients, but successful selective CBD cannulation was achieved in 12
      patients (92.3%). Median maximum transverse stone size was 11.5 mm (10 to 14 mm).
      The mean number of stones was 2 (1-5). The median CBD diameter was 15 mm (12 to
      19 mm). Mean procedure time from successful biliary access to complete stone
      removal was 17.8 min. Complete duct clearance was achieved in all patients. Four
      patients (33.3%) needed one more session of ERCP for removal of remnant stones.
      Asymptomatic hyperamylasemia in two patients and minor bleeding in another
      occurred. CONCLUSIONS: Without preceding sphincterotomy, one-step EPBD (>=10 mm)
      under cap-fitted forward-viewing endoscopy may be safe and effective for the
      removal of large stones (>=10 mm) with CBD dilatation in Billroth II gastrectomy.

PMID- 22375181
TI  - A case of synchronous squamous cell carcinoma in the esophagus and stomach.
AB  - Synchronous esophageal and gastric cancers with the pathologic features of a
      squamous cell carcinoma are extremely rare. A 57-year-old male visited our
      hospital with a history of hematemesis and was diagnosed with a synchronous
      cancer. He underwent a staging work-up, and the resectable lesion in the stomach
      was operated on following radiologic and endoscopic evaluations. The pathologic
      examination revealed a synchronous cancer consisting of squamous cell carcinoma
      in the distal esophagus and the cardia of the stomach. We report a case of a
      synchronous cancer that was successfully treated by surgical resection followed
      by concurrent chemoradiotherapy. We also discuss the hypothesis regarding the
      origin and presentation of the synchronous cancer and highlight the importance of
      careful surveillance by physicians at the time of diagnosis.

PMID- 22375182
TI  - Endoscopic treatment of duodenal bleeding caused by direct hepatocellular
      carcinoma invasion with an ethanol injection.
AB  - We report a case of a man who developed duodenal bleeding caused by direct
      hepatocellular carcinoma (HCC) invasion, which was successfully treated with
      endoscopic ethanol injection. A 57-year-old man with known HCC was admitted for
      melena and exertional dyspnea. He had been diagnosed with inoperable HCC a year
      ago. Urgent esophagogastroduodenoscopy (EGD) showed two widely eroded mucosal
      lesions with irregularly shaped luminal protruding hard mass on the duodenal
      bulb. Argon plasma coagulation and Epinephrine injection failed to control
      bleeding. We injected ethanol via endoscopy to control bleeding two times with 14
      cc and 15 cc separately without complication. Follow-up EGD catched a large ulcer
      with necrotic and sclerotic base but no bleeding evidence was present. He was
      discharged and he did relatively well during the following periods. In
      conclusion, Endoscopic ethanol injection can be used as a significantly effective
      and safe therapeutic tool in gastrointestinal tract bleeding caused by HCC
      invasion.

PMID- 22375183
TI  - A Novel Frameshift Mutation of the ALDOB Gene in a Korean Girl Presenting with
      Recurrent Hepatitis Diagnosed as Hereditary Fructose Intolerance.
AB  - Hereditary fructose intolerance is an autosomal recessive disorder that is caused
      by a deficiency in fructose-1-phosphate aldolase (Aldolase B). Children can
      present with hypoglycemia, jaundice, elevated liver enzymes and hepatomegaly
      after intake of dietary fructose. Long-term intake of fructose in undiagnosed
      patients can result in hepatic failure or renal failure. We experienced a case of
      hereditary fructose intolerance presenting as recurrent hepatitis-like episodes.
      Detailed evaluation of her dietary habits revealed her avoidance of sweetened
      foods and fruits. Genetic analysis of ALDOB revealed that she is a homozygote for
      a novel frameshifting mutation c[758_759insT]+[758_759insT] (p.[val25
      3fsX24]+[val253fsX24]). This report is the first of a Korean patient diagnosed
      with hereditary fructose intolerance using only molecular testing without
      undergoing intravenous fructose tolerance test or enzyme assay.

PMID- 22375184
TI  - A rare case of a signet ring cell carcinoma of the colon mimicking a juvenile
      polyp.
AB  - Primary signet ring cell carcinoma (SRC) of colon at early stage is quite rare.
      Only 26 cases were reported until now. We report an early stage of primary SRC
      which was misdiagnosed as a juvenile polyp and treated with polypectomy followed
      by surgical resection. A 21-year-old male was administered for hematochezia.
      Abdominopelvic enhanced computed tomography revealed a polyp with active bleeding
      at the proximal rectum just below the rectosigmoid junction. Colonoscopy
      examination revealed a colon polyp with 0.5 cm sized head. Polypectomy was
      performed with snare and the polyp was completely removed. Biopsy revealed SRC.
      Surgical resection was also performed and there were no residual tumor or lymph
      node metastasis in the surgical specimen.

PMID- 22375185
TI  - A Case of Autoimmune Pancreatitis Manifested by a Pseudocyst and IgG4-Associated
      Cholangitis.
AB  - Autoimmune pancreatitis (AIP) is a benign disorder and a unique form of chronic
      pancreatitis with several characteristic features. A cystic formation that mimics
      a pseudocyst is a rare finding. There have been a few reports of AIP complicated
      by pancreatic cysts. We present a case of AIP with multiple pseudocysts and
      obstructive jaundice caused by IgG4-associated cholangitis. We initially missed
      the diagnosis due to the pseudocyst. Based on the computed tomography images,
      laboratory findings and the therapeutic response to steroids, the case was
      diagnosed as AIP with pseudocysts and associated cholangiopathy.

PMID- 22375186
TI  - The Successful Treatment of Chronic Cholecystitis with SpyGlass Cholangioscopy
      Assisted Gallbladder Drainage and Irrigation through Self-Expandable Metal
      Stents.
AB  - A 34-year-old female with a history of advanced pulmonary sarcoidosis and right
      sided heart failure presented with chronic, postprandial right upper quadrant
      pain, and weight loss. Endoscopic biliary drainage was deemed to be the most
      appropriate therapeutic option for her chronic cholecystitis. Endoscopic
      retrograde cholangiopancreatography utilizing the SpyGlass cholangioscopy system
      allowed us to access the cystic duct through which the gallbladder was ultimately
      decompressed, via biliary stent placement and gallstone irrigation. This is the
      first report of SpyScope assisted placement of fully covered self-expandable
      metal biliary stents into the cystic duct enabling definitive treatment of
      symptomatic chronic cholecystitis and cholelithiasis without cholecystectomy.

PMID- 22375187
TI  - Effect of training on physiological and biochemical variables of soccer players
      of different age groups.
AB  - PURPOSE: To find out the effect of training on selected physiological and
      biochemical variables of Indian soccer players of different age groups. METHODS:
      A total of 120 soccer players volunteered for the study, were divided (n = 30)
      into 4 groups: (i) under 16 years (U16), (ii) under 19 years (U19), (iii) under
      23 years (U23), (iv) senior (SR). The training sessions were divided into 2
      phases (a) Preparatory Phase (PP, 8 weeks) and (b) Competitive Phase (CP, 4
      weeks). The training program consisted of aerobic, anaerobic and skill
      development, and were completed 4 hrs/day; 5 days/week. Selected physiological
      and biochemical variables were measured at zero level (baseline data, BD) and at
      the end of PP and CP. RESULTS: A significant increase (P < 0.05) in lean body
      mass (LBM), VO(2max), anaerobic power, grip and back strength, urea, uric acid
      and high density lipoprotein cholesterol (HDL-C); and a significant decrease (P <
      0.05) in body fat, hemoglobin (Hb), total cholesterol (TC), triglyceride (TG) and
      low density lipoprotein cholesterol (LDL-C) were detected in some groups in PP
      and CP phases of the training when compare to BD. However, no significant change
      was found in body mass and maximal heart rate of the players after the training
      program. CONCLUSION: This study would provide useful information for training and
      selection of soccer players of different age groups.

PMID- 22375188
TI  - Injury rates in Iranian taekwondo athletes; a prospective study.
AB  - PURPOSE: Taekwondo, as the most popular martial art among Iranian sportsmen,
      might lead to injury for the athletes of this sport during competitions. We
      decided to report the incidence rate of injuries sustained by the athletes of
      this sport during national competitions. METHODS: All competitions of Iran
      national championship taekwondo league in 2006-2007 with 204 athletes were
      observed prospectively to detect the occurrence of injuries. The severity of
      injuries was classified into four groups (mild, moderate, severe, and critical)
      according to the involvement of medical care team in the contest, ability of the
      athletes to resume and duration of probable absence of injured athletes from
      future competitions and training sessions. Athlete-Exposure (A-E) was defined as
      the number of competitions multiplied by two. On this base, the rate of injury
      incidence per 1000 A-Es, the rate of injuries per time unit and the rate of
      injury occurred for each 100 athletes were considered as the major outcomes of
      this study. RESULTS: Of totally 1,338 A-Es, 93 injuries were recorded during the
      competitions. The rate of injury incidence was found to be 69.5 injuries per 1000
      A-Es and the rate of injuries per minute of competitions was 0.023 which
      corresponded to 23.3 injuries per 1000 minutes of competitions. 45.6 injuries
      were occurred for each 100 athletes during the course of competitions. The most
      frequent injuries were mild (68.8%) and critical injuries (24.7%), followed by
      moderate and severe injuries; 4.3% and 2.1%, respectively. CONCLUSION: The rate
      of injury we found was lower than that of western countries. In spite of finding
      the lower limbs as the most frequent place of injuries in other studies, we found
      the upper limbs as the most predisposed place of injuries which might be due to
      difference in the method of combat of Iranian athletes with other athletes.

PMID- 22375189
TI  - Pre-participation Cardiovascular Screening of Elderly Wrestlers.
AB  - PURPOSE: Sudden death of a competitive athlete is a tragedy that is usually
      caused by a previously unsuspected cardiovascular disease. The aim of this study
      was to clarify the role of noninvasive testing in pre-participation
      cardiovascular evaluation of elderly wrestlers. METHODS: We included 63 Iranian
      elderly wrestlers who participated in Tehran international elderly wrestlers'
      preparation camping by census method. A questionnaire including past medical and
      family history as well as coronary risk factors was filled out and then a
      complete physical examination of the cardiovascular system was done by an
      internist for all wrestlers. Electrocardiogram (ECG), complete echocardiographic
      examination and then symptom limited exercise test were performed and reported by
      the cardiologists who did not know the other examinations results. RESULTS:
      Exertional dyspnea and typical chest pain (FC=I or II) were present in 5% and
      1.7% of the examinees, respectively. There were one or more risk factors in 64.5%
      of the cases. Cardiovascular examination revealed abnormal heart sounds in 27.1%.
      ECG showed ischemic changes in 13.6% and premature atrial contractions and
      premature ventricular contractions in 11.4%. Echocardiography showed mild left
      ventricular systolic dysfunction in 3.4%, regional wall motion abnormality in
      8.5%, valvular disease in 32.3%, diastolic dysfunction in 45.7%, and left
      ventricular hypertrophy in 16.9% of the cases. Exercise test results were
      negative, equivocal, positive and highly positive in 70.4%, 15.8%, 5.2%, and 8.6%
      of cases, respectively. CONCLUSION: Beside physical examination, pre
      participation screening of elderly wrestling athletes with ECG and exercise
      testing is feasible and recommended in the presence of coronary risk factors or
      cardiac symptoms. Echocardiography can also be recommended to detect other
      relevant abnormalities when there is a clue in the standard history, physical
      examination or ECG.

PMID- 22375190
TI  - The Effect of Exercise in PCOS Women Who Exercise Regularly.
AB  - PURPOSE: To determine the prevalence of polycystic ovary syndrome (PCOS) in women
      who exercise regularly. METHODS: All women under age 45 from an industrial
      company who had past history of exercising more than 6 months enrolled in this
      cross-sectional study. Prevalence of PCOS and comparison of BMI between PCOS and
      non-PCOS subgroups was done. The diagnosis of PCOS was based on the revised 2003
      Rotterdam ESHRE/ASRM consensus criteria and exclusion of related disorders.
      RESULTS: The prevalence of PCOS in was 8.8%; 95% CI: 8.5%-9.1%. In obese
      subjects, mean BMI differed significantly between PCOS and non-PCOS women (29.3
      +/-3.3 kg/m(2) vs. 27.8 +/- 2 kg/m(2), P=0.03). In lean subjects, there was no
      statistically significant difference in terms of BMI between PCOS and non-PCOS
      women (21.4 +/- 1.9 kg/m(2) vs. 21.2 +/- 2 kg/m(2), P>0.05). CONCLUSION: Obese
      PCOS patients show more difficulty in losing weight by exercise than lean PCOS
      patients. The role of hormonal alterations and PCOS per se in the responsiveness
      of weight loss to exercise remains to be determined.

PMID- 22375191
TI  - A regression equation for the estimation of maximum oxygen uptake in nepalese
      adult females.
AB  - PURPOSE: Validity of the 20-meter multi stage shuttle run test (20-m MST) has not
      been studied in Nepalese population. The purpose of this study was to validate
      the applicability of the 20-m MST in Nepalese adult females. METHODS: Forty
      female college students (age range, 20.42 ~24.75 years) from different colleges
      of Nepal were recruited for the study. Direct estimation of VO(2) max comprised
      treadmill exercise followed by expired gas analysis by scholander micro-gas
      analyzer whereas VO(2) max was indirectly predicted by the 20-m MST. RESULTS: The
      difference between the mean (+/-SD) VO(2) max values of direct measurement (VO(2)
      max = 32.78 +/-2.88 ml/kg/min) and the 20-m MST (SPVO(2) max = 32.53 + /-3.36
      ml/kg/min) was statistically insignificant (P>0.1). Highly significant
      correlation (r=0.94, P<0.01) existed between the maximal speed of the 20-m MST
      and VO(2) max. Limits of agreement analysis also suggest that the 20-m MST can be
      applied for the studied population. CONCLUSION: The results of limits of
      agreement analysis suggest that the application of the present form of the 20-m
      MST may be justified in the studied population. However, for better prediction of
      VO(2) max, a new equation has been computed based on the present data to be used
      for female college students of Nepal.

PMID- 22375193
TI  - Sport and eating disorders - understanding and managing the risks.
AB  - There is strong and consistent evidence that eating disorders are prevalent in
      sport and especially in weight sensitive sports such as endurance, weight
      category and aesthetic sports as well as jumping events. These illnesses are not
      only common but lead to significant physical and psychological morbidity and
      impaired performances.Sports organizations, and by extension the professionals
      whose job it is to help and support athletes, have important roles in dealing
      with these conditions. Preventative practices can be adopted if there is an
      understanding of how the sports environment contributes to the development of
      eating disorders. Some disorders can be difficult to detect especially in a
      sports environment and simple screening instruments are available. Athletes may
      also need help to access appropriate treatment whilst they are recovering.In many
      sports prevention, screening and support programs have been developed for a
      variety of medical conditions or sportsrelated injuries. Similar programs should
      be developed for eating disorders.

PMID- 22375192
TI  - Angular deformities of the lower limb in children.
AB  - Angular deformities of the lower limbs are common during childhood. In most cases
      this represents a variation in the normal growth pattern and is an entirely
      benign condition. Presence of symmetrical deformities and absence of symptoms,
      joint stiffness, systemic disorders or syndromes indicates a benign condition
      with excellent long-term outcome. In contrast, deformities which are asymmetrical
      and associated with pain, joint stiffness, systemic disorders or syndromes may
      indicate a serious underlying cause and require treatment.Little is known about
      the relationship between sport participation and body adaptations during growth.
      Intense soccer participation increases the degree of genu varum in males from the
      age of 16. Since, according to some investigations, genu varum predisposes
      individuals to more injuries, efforts to reduce the development of genu varum in
      soccer players are warranted. In this article major topics of angular deformities
      of the knees in pediatric population are practically reviewed.

PMID- 22375194
TI  - Critical appraisal and hazards of surface electromyography data acquisition in
      sport and exercise.
AB  - The aim of this critical appraisal and hazards of surface electromyography (SEMG)
      is to enhance the data acquisition quality in voluntary but complex movements,
      sport and exercise in particular. The methodological and technical registration
      strategies deal with telemetry and online data acquisition, the placement of the
      detection electrodes and the choice of the most adequate normalization
      mode.Findings compared with the literature suggest detection quality differences
      between registration methods and between water and air data acquisition allowing
      for output differences up to 30% between registration methods and up to 25%
      decrease in water, considering identical measures in air and in water. Various
      hazards deal with erroneous choices of muscles or electrode placement and the
      continuous confusion created by static normalization for dynamic motion. Peak
      dynamic intensities ranged from 111% (in archery) to 283% (in giant slalom) of a
      static 100% reference. In addition, the linear relationship between integrated
      EMG (IEMG) as a reference for muscle intensity and muscle force is not likely to
      exist in dynamic conditions since it is muscle - joint angle - and fatigue
      dependent. Contrary to expectations, the literature shows 30% of non linear
      relations in isometric conditions also.SEMG in sport and exercise is highly
      variable and different from clinical (e.g. neurological) EMG. Choices of
      electrodes, registration methods, muscles, joint angles and normalization
      techniques may lead to confusing and erroneous or incomparable results.

PMID- 22375195
TI  - Prevention of football injuries.
AB  - PURPOSE: Every sport has a unique profile of injury and risk of injury. In recent
      years, there have been numerous attempts at conducting injury prevention trials
      for specific injuries or for injuries within specific sports to provide evidence
      useful to the sports medicine and sport community. Football has been a focus of a
      number of randomized injury prevention trials. METHODS: MEDLINE was searched with
      the first order keywords of "injury prevention" and "sport". This list was
      restricted to "clinical trial" or "randomized controlled trial" which had been
      conducted on children and adults whose goal was preventing common football
      injuries. Our objective was to find studies with an exercise-based training
      program, thus projects that used mechanical interventions were excluded. RESULTS:
      A structured, generalized warm-up has been shown to be effective at preventing
      common injuries in football, reducing injuries by about one-third. CONCLUSION:
      The huge participation numbers in the worldwide family of football would suggest
      that any reduction in injury should have a public health impact. Professionals in
      sports medicine need to promote injury prevention programs that have been shown
      to be effective.

PMID- 22375196
TI  - Nutrition knowledge, attitude and practice of college sportsmen.
AB  - PURPOSE: Nutrition is an important component of any physical fitness program. The
      main dietary goal for active individuals is to obtain adequate nutrition to
      optimize health fitness and to increase sports performance. The present study
      aims to assess the nutrition knowledge, attitude and practice among the selected
      athletes. METHODS: Athletes from five different private colleges situated in
      Salem District, Tamilnadu, India were selected. A total number of 102 athletes,
      32 sportsmen belong to Volleyball discipline, 25 belongs to weightlifter
      discipline and 45 belong to runners discipline in sports. All the selected
      athletes were including in the study. The Knowledge, Attitude and Practice (KAP)
      questionnaire contained ten questions about nutrition knowledge, nine questions
      about attitudes, and ten questions about dietary practice were collected from the
      selected athletes. Dietary composition of the sportsmen is also assessed. The
      collected data was coded and used for evaluation. RESULTS: Results about KAP
      revealed that 42 per cent of the volleyball players had good nutritional
      knowledge (60-69per cent) compared to weight lifters (43per cent) who had
      satisfactory (50-59per cent) knowledge about nutrition. Twenty nine per cent of
      the runners had very good (70-79per cent) knowledge about nutrition. Regarding
      food consumption pattern intake of cereals, other vegetables and milk was found
      to be less compared to the RDA for the athletes. Among the three disciplines
      sports persons, the mean nutrient intake of the runners is high compared to
      volleyball and weight lifters. CONCLUSION: The sports disciplines strongly
      affected the nutrition knowledge, attitudes and practices of sportsmen. The
      overall scores indicate that most sportsmen had good knowledge of nutrition and
      supplements.

PMID- 22375198
TI  - Studying wind chill index as a climatic index effective on the health of athletes
      and tourists interested in winter sports.
AB  - PURPOSE: Estimating wind chill index as one of the indexes effective in body
      comfort, specifically for athletes and tourists interested in winter sports.
      METHODS: Meteorology data including temperature and the percentage of relative
      humidity of 6 synoptic stations of Chaharmahal-Bakhtiyrai province, Iran from
      1990 to 2007 were extracted from Iranian Meteorology Site. In order to calculate
      the values of wind chill, the innovative formula of NOAA Meteorology Services
      Center [T (WC)= 35.74+0.6215T-35.75V+0.4275TV] was used. RESULTS: After analyzing
      wind in all stations, it became evident that the great percentage of wind calm
      related to fall, and spring had the most wind distortions. In studying the mean
      temperature during this studying period, Koohrang station with mean of 9.8
      degrees C was identified as the coldest station and Lordegan with a mean of 17
      degrees C represented the warmest station of the region observed. According to
      degrees derived from wind chill index, Koohrang station in January with a mean of
      -28.75 was known as the coldest and roughest station. CONCLUSION: Among the
      studied stations, Koohrang had the most intensive degrees of wind chill
      occurrence and Lordegan had the calmest conditions. Therefore, athletes and
      tourists should use warmer clothes and covers in cold seasons in Koohrang in
      comparison with other studied regions, in order to protect themselves from the
      negative effects of sudden cold and occurrence of intense wind chills.

PMID- 22375197
TI  - Prediction equation for calculating fat mass in young Indian adults.
AB  - PURPOSE: Accurate measurement or prediction of fat mass is useful in physiology,
      nutrition and clinical medicine. Most predictive equations currently used to
      assess percentage of body fat or fat mass, using simple anthropometric
      measurements were derived from people in western societies and they may not be
      appropriate for individuals with other genotypic and phenotypic characteristics.
      We developed equations to predict fat mass from anthropometric measurements in
      young Indian adults. METHODS: Fat mass was measured in 60 females and 58 males,
      aged 20 to 29 yrs by using hydrostatic weighing and by simultaneous measurement
      of residual lung volume. Anthropometric measure included weight (kg), height (m)
      and 4 skinfold thickness [STs (mm)]. Sex specific linear regression model was
      developed with fat mass as the dependent variable and all anthropometric measures
      as independent variables. RESULTS: The prediction equation obtained for fat mass
      (kg) for males was 8.46+0.32 (weight) - 15.16 (height) + 9.54 (log of sum of 4
      STs) (R2= 0. 53, SEE=3.42 kg) and - 20.22 + 0.33 (weight) + 3.44 (height) + 7.66
      (log of sum of 4 STs) (R2=0.72, SEE=3.01kg) for females. CONCLUSION: A new
      prediction equation for the measurement of fat mass was derived and internally
      validated in young Indian adults using simple anthropometric measurements.

PMID- 22375199
TI  - Ramadan fasting and exercise performance.

PMID- 22375200
TI  - Is body fat a predictor of race time in female long-distance inline skaters?
AB  - PURPOSE: The aim of this study was to evaluate predictor variables of race time
      in female ultra-endurance inliners in the longest inline race in Europe. METHODS:
      We investigated the association between anthropometric and training
      characteristics and race time for 16 female ultra-endurance inline skaters, at
      the longest inline marathon in Europe, the 'Inline One-eleven' over 111 km in
      Switzerland, using bi- and multivariate analysis. RESULTS: The mean (SD) race
      time was 289.7 (54.6) min. The bivariate analysis showed that body height
      (r=0.61), length of leg (r=0.61), number of weekly inline skating training
      sessions (r=-0.51) and duration of each training unit (r=0.61) were significantly
      correlated with race time. Stepwise multiple regressions revealed that body
      height, duration of each training unit, and age were the best variables to
      predict race time. CONCLUSION: Race time in ultra-endurance inline races such as
      the 'Inline One-eleven' over 111 km might be predicted by the following equation
      (r(2)=0.65): Race time (min)=-691.62+521.71 (body height, m)+0.58 (duration of
      each training unit, min)+1.78 (age, yrs) for female ultra-endurance inline
      skaters.

PMID- 22375201
TI  - Effects of exercise on memory consolidation and retrieval of passive avoidance
      learning in young male rats.
AB  - PURPOSE: Previous studies have shown that physical activity improves learning and
      memory. Present study was performed to determine the effects of short term and
      long term treadmill exercise on learning, memory consolidation and retrieval of
      passive avoidance learning in an animal model. METHODS: In this study fifty male
      Wistar rats with 3-4 months of age were randomly divided into five groups (n=10
      in each group). Control group was trained in passive avoidance box and was tested
      10 min, 24 hr, 10 days and 3 months later. Two groups exercised on treadmill one
      hour at 17 m. min for 10 days and 3 months respectively and then were trained in
      passive avoidance box and were tested 10 min and 24 hr later. The other two
      groups were trained and were tested 10 days and 24 hr later and then exercised on
      treadmill as same as other exercised groups. RESULTS: Obtained results showed
      that short-term (10 days) and long-term (3 months) treadmill running before
      training by passive avoidance test had significant (P=0.006 and P=0.001
      respectively) effects on memory consolidation. However, no significant difference
      was observed between latency time of rats before and after exercise in exercised
      groups retrieval (P>0.05). CONCLUSION: Our results showed that physical activity
      promoted learning and memory consolidation but it did not affect retrieval memory
      performance.

PMID- 22375202
TI  - Association of Angiotensin Converting Enzyme gene Polymorphism and Indian Army
      Triathletes Performance.
AB  - PURPOSE: It is well known that the effects of exercise training gives inter
      individual differences which might be due to genetic diversity. This study aims
      to explore the probable relation between angiotensin converting enzyme (ACE)
      alleles and physical fitness parameters in elite athletes. METHODS: Twenty-nine
      national level Indian Army Triathletes who volunteered for the study were taken
      as subjects and 101 healthy age matched control group subjects were taken for
      comparison of genotype frequencies. The following parameters were checked in
      triathletes: blood pressure, body mass index, VO(2 max), muscular endurance,
      flexibility and power. DNA was extracted from blood using standard phenol
      chloroform method. Genotyping was done using PCR specific for ACE (I/D)
      polymorphism, followed by agarose gel electrophoresis method. Variation of the
      parameters among different genotypes was compared. Genotype frequencies of
      triathletes were compared with the control group as well. RESULTS: No difference
      was observed between fitness parameters of three genotype groups' triathletes,
      while the frequency of I allele was found to be very high in triathletes compared
      with the control group. CONCLUSION: It can be concluded that there might be a
      positive association between I allele of ACE gene and endurance.

PMID- 22375203
TI  - Twelve-week aerobic training decreases chemerin level and improves
      cardiometabolic risk factors in overweight and obese men.
AB  - PURPOSE: The inflammatory state of adipose tissue in obese subjects may be the
      most important factor linking increased adipose tissue mass to insulin
      resistance. Chemerin is a newly discovered adipokine that plays an important role
      in macrophage infiltration into adipose tissue and may contribute to the
      development of inflammation and insulin resistance. We examined the effects of 12
      weeks of aerobic training on serum chemerin levels in association with
      cardiovascular risk factors in overweight and obese males. METHODS: Twenty-one
      overweight and obese subjects [44.3 (+/-4.1 yrs, body mass index (BMI) >=25
      kg/m(2)) were assigned to exercise training (obese EX, n= 11) and control (obese
      CON, n= 10) groups. The obese EX group participated in 12 weeks of progressive
      aerobic training 5 days a week. Serum chemerin, insulin resistance, lipid
      profiles, blood pressure, and body composition were all measured before and after
      the training. RESULTS: After the aerobic training, waist circumference (P=0.009),
      fat percent (P=0.03), visceral fat (P=0.03), subcutaneous fat (P=0.01), fasting
      glucose (P=0.01), insulin resistance (P=0.03), triglyceride (P=0.05), total
      cholesterol (P=0.04), low-density lipoprotein cholesterol (P=0.05) and systolic
      blood pressure (P=0.04) of participates were significantly decreased.
      Concurrently, serum chemerin concentrations were significantly decreased after
      aerobic program (P=0.02). CONCLUSION: Aerobic training caused an improvement in
      cardiometabolic risk factors in obese subjects, and this improvement was
      accompanied by decreased chemerin levels.

PMID- 22375204
TI  - The effects of a 10-week water aerobic exercise on the resting blood pressure in
      patients with essential hypertension.
AB  - PURPOSE: To investigate the effects of a 10-week water aerobic exercise on the
      resting blood pressure in patients with stage 1 or 2 hypertension referring to
      Tehran University Clinics. METHODS: Forty men with stage 1 or 2 essential
      hypertension were assigned to two groups of intervention [n = 12; aged 48.33+/
      10.74 years (mean+/-SD)] and control [n = 28; aged 46.96+/-11.58 years (mean+/
      SD)]. Subjects in the intervention group participated in a supervised 10-week
      water aerobic training program of 55 min sessions, 3 days per week on alternate
      days, while those in the control group were not involved in any regular training
      program during this period. Blood pressure of the participants was recorded and
      compared at the beginning and at the end of the study (48 hours after the last
      training session). RESULTS: Exercise lowered systolic blood pressure and mean
      arterial pressure by 11.71 (95% confidence interval: 5.07 to 18.35) and 5.90 (95%
      confidence interval: 1.17 to 10.63) mm Hg respectively. The lowering effect of
      exercise on diastolic blood pressure was neither statistically significant nor
      clinically important (0.55 mm Hg; P. value = 0.8). There was no significant
      effect of age, baseline body mass index and stage of hypertension on the exercise
      induced changes in blood pressure. CONCLUSION: A 10-week course of water aerobic
      exercise markedly reduced the systolic and mean arterial blood pressure of
      patients with essential hypertension and is especially recommended for the obese
      and the elderly who have orthopedic problems or bronchospasm.

PMID- 22375205
TI  - The effects of aerobic versus resistance training on cardiovascular fitness in
      obese sedentary females.
AB  - PURPOSE: The present study was designed to evaluate the effects of aerobic and
      strength training on cardiac variables such as blood pressure, heart rate (HR),
      and metabolic parameters like cholesterol, high density lipoprotein (HDL),
      triglycerides and anthropometric parameters of obese women of Punjab. METHODS:
      This study was performed as an experimental study, in which subjects were
      randomly selected. There were thirty obese women, aged between 35-45yrs with body
      mass index (BMI) of above 30. Subjects were grouped into control (n=10), aerobic
      training (n=10) and resistance training (n=10). Aerobic training was given for
      three days a week at 60-70% of maximum HR for 6 weeks. Resistance training
      (Delorme and Watkins Technique) was given for alternate days for 6 weeks. HR and
      blood pressure were measured before and after the exercise. Recovery HR was also
      measured. RESULTS: The findings of the study indicate statistically significant
      differences in recovery heart rate [Pre-exercise: 97.40+/- 5.378 (mean+/-standard
      deviation (SD)), post-exercise: 90.70+/-4.599, t=8.066, P<0.001] and in post
      diastolic blood pressure [Pre-exercise: 85+/-3.265, post-exercise: 86.20+/-2.820,
      P<0.001] in aerobic training and in systolic blood pressure [Pre- and post
      exercise] in both training groups (P<0.001). Significant differences were
      observed in very low-density lipoprotein [pre-exercise: 28.10+/-1.415, post
      exercise: 26.86+/-0.760, t=5.378] and HDL [pre-exercise: 45.40+/-3.533, post
      exercise: 53.60+/-3.134, t=6.318] levels in aerobic training group with P<0.001.
      BMI and body fat percentage showed significant improvements in both training
      groups. CONCLUSION: Aerobic training is more beneficial and can be used as a
      preventive measure in patients who are at risk of developing cardiovascular
      diseases due to obesity.

PMID- 22375206
TI  - Factorial validation of malaysian adapted brunel mood scale in an adolescent
      sample.
AB  - PURPOSE: The present study investigated the psychometric properties of a
      Malaysian adapted Brunel Mood Scale. METHODS: The questionnaire was administered
      to 355 young sport athletes with a mean age of 14.69+1.70 years. Confirmatory
      factor analysis (CFA) and Cronbach's alpha were used to determine the factorial
      validity and the internal consistency of the questionnaire respectively. RESULTS:
      CFA results revealed adequate model fit, best represented by a 6-factor model
      with one of the items removed (item 24). Internal consistency of the
      questionnaire was marginally supported through alpha reliability method. Alpha
      coefficients of 0.72, 0.64, 0.73, 0.69, 0.65, and 0.58 were obtained for tension,
      depression, anger, vigour, fatigue and confusion subscales respectively. Closer
      inspection of items for confusion revealed a 'problematic' item (item
      24/uncertain). Removing this item increased the alpha coefficient to 0.67 for
      this subscale. CONCLUSION: It was concluded that this questionnaire may be used
      to measure differentiated negative and positive mood states among Malaysian
      adolescent athletes. However, further analyses involving independent samples are
      needed to confirm the present findings.

PMID- 22375207
TI  - Relationships between Exercise as a Mood Regulation Strategy and Trait Emotional
      Intelligence.
AB  - PURPOSE: The aim of this study was to investigate the relationship between
      perception of emotional intelligence and beliefs in the extent to which
      exercising leads to mood-enhancement. METHODS: Volunteer participants (N=315)
      completed a 33-item self-report measure of trait emotional intelligence and an
      exercise-mood regulation scale. RESULTS: Emotional intelligence significantly
      correlated with beliefs that exercise could be used to regulate mood (r =0.45,
      P<0 .01). CONCLUSION: Findings demonstrate that using exercise to regulate mood
      relates significantly to emotional intelligence and suggest that individuals who
      use exercise to enhance mood report higher scores of emotional intelligence.

PMID- 22375208
TI  - Injury profile of a professional soccer team in the premier league of iran.
AB  - PURPOSE: Despite numerous studies which have been done regarding soccer injuries
      worldwide, there is lack of available data considering the epidemiology of
      injuries in the Iranian soccer premier league, although it is the most popular
      sport in the country. The main goal of this research was to determine the
      incidence of physical injuries in the studied population, considering other
      characteristics such as site, type and mechanism as well. METHODS: Twenty one
      adult male professional soccer players (age 24+/-3), members of a team (Tehran
      Pas) participating in Iranian premier league, were followed during a 4-month
      period. The injury characteristics and exposure times were recorded by the team
      physician during all the matches and training sessions. RESULTS: The total
      exposure time was 2610 playing hours (2352 h of training versus 258 h of
      competition). Eighty six percent of the injuries were acute. Incidence of acute
      injuries was 16.5 (95% CI: 12-22) per 1000 hours of playing (11.5 per 1000 hrs of
      training and 62 per 1000 hrs of competition). The most common types of injuries
      were strains followed by contusions, each of which constituted 30% of acute
      injuries. More than 80% of injuries occurred in lower limbs, especially in thigh
      and groin regions. Nearly 60% of acute injuries occurred in dominant side of the
      body, and collision was the reason of about half of the acute injuries. Severity
      of more than 70% of the injuries was minor. On average each injury had led the
      player being off the field for about 10 days. CONCLUSION: The incidence of injury
      in this research is in range of numbers obtained in important international
      tournaments but the rate of injuries during training sessions is higher than
      comparable studies.

PMID- 22375209
TI  - The effects of exercise in obese women with bulimia nervosa.
AB  - PURPOSE: Obesity has been identified as a risk factor for the development of
      bulimia nervosa (BN) in those who try to lose weight. The purpose of the present
      study was to examine the effect of walking exercise in order to provide a method
      for overcoming bulimia nervosa in obese young women suffering from bulimia
      nervosa. METHODS: Twenty obese women with bulimia nervosa (body mass index
      [BMI]>30) and a mean age of 22.00+/-1.50 years volunteered to participate in this
      study. They were randomly assigned to exercise (n=10) and control (n=10) groups.
      Both groups underwent anthropometric measurements and blood analysis before and
      after the training program. Exercise program included 30-minute walking sessions
      at 50-75% of maximal heart rate, 3 days per week and for 2 months. RESULTS: After
      2 months significant changes were observed in all anthropometric variables
      (P<0.001). Percent body fat, fat mass, BMI, body weight and lean mass changes in
      response to training were significant in the exercise group (P<0.001).
      CONCLUSION: This study demonstrated that moderate aerobic exercises such as
      moderate walking are suitable behavior therapies for overcoming bulimia nervosa
      in obese young women.

PMID- 22375210
TI  - Risk Factors of Adolescent Obesity in Taiwan and Its Association with Physical
      activity, Blood Pressure and Waist Circumference.
AB  - PURPOSE: This study was conducted to investigate risk factors of obesity and its
      associated health problems in adolescence in Taiwan. METHODS: We enrolled 559
      adolescent volunteers with equal numbers of females and males in 2008.
      Participants were divided into two groups: obese (body mass index [BMI] ?95th
      percentile) and normal-weight adolescents (BMI: 15th ~ 85th percentile). Each of
      them completed a questionnaire about lifestyle and parents' stature. RESULTS:
      Obese mother had high likelihood of having obese girls and boys (P=0.001). Obese
      girls spent more time in watching TV (P=0.03) and had higher frequency of having
      sweetened soft drinks (P=0.016) than normal-weight group. Girls spent more time
      in TV watching associated higher frequency of having sweetened soft drinks
      (P=0.012). In boys, this associated with higher frequency of eating snick
      (P=0.018) and larger waist circumference (P=0.011). Boys who had more frequent
      effective exercise had lower frequency of eating outside (P=0.01) and more
      services of vegetables (P=0.002). There was no relation between hypertension and
      adolescent physical activity. Regardless of gender, obese group had higher waist
      circumference and blood pressure than normal-weight group (P<0.001). CONCLUSION:
      There was a strong association between obese mother and adolescent obesity. More
      physical activity in adolescents associated with healthier dietary behaviors.
      Obese adolescents have higher waist circumference and blood pressure.

PMID- 22375211
TI  - Completing an ironman triathlon with pneumonia: a case report.
AB  - BACKGROUND: Athletes present a different category of the population. Trivial
      complaints may mask more serious illness, especially when the athlete is
      undergoing intensive training, and the function of his immune system may be sub
      optimal. CASE PRESENTATION: A triathlete presented a few days after completing an
      Ironman race, complaining of lethargy, pleuritic chest pain and loss of appetite.
      On examination he was afebrile, tachycardic and had decreased lower left lung air
      entry accompanied by crackling. A chest x-ray revealed left-sided basal pneumonia
      with a para-pneumonic effusion. Blood tests were unremarkable. The athlete was
      treated with oral antibiotics, and was advised to stop exercise completely for
      eight weeks. He made a full recovery and completed further Ironman races within a
      year. CONCLUSION: The case highlights that clinicians treating elite endurance
      athletes must exclude severe infection, even when the clinical signs are few or
      absent. The reason is that if these athletes continue to train, serious
      complications could ensue due to their compromised resistance to infection.

PMID- 22375212
TI  - Sudden cardiac death in young athletes; a literature review and special
      considerations in Asia.
AB  - Sudden cardiac death (SCD) in a young athlete is rare, but catastrophic. Exercise
      acts as a risk factor for SCD in people with cardiovascular disease. A diversity
      of cardiovascular disorders including hypertrophic cardiomyopathy, congenital
      coronary anomalies, arrhythmogenic right ventricular dysplasia, dilated
      cardiomyopathy, aortic rupture due to Marfan syndrome, myocarditis, valvular
      disease and electrical disorders (Wolff-Parkinson-White syndrome, long QT
      syndrome, Brugada syndrome), as well as commotio cordis represent the common
      causes of SCD in young athletes.As the outcome of lethal cardiovascular disorders
      is not reversible except in few cases, effective measures should be addressed to
      reduce the burden of sudden cardiac death in young athletes. Currently, two types
      of recommendations are proposed by American and European countries.It seems that
      there are some special considerations in Asia, entirely different from North
      America or Europe, which warrant more comprehensive research on epidemiology and
      etiology of SCD in young Asian athletes by country and evaluation of current
      national preventive strategies and their achievements in decreasing the risk.
      Using these data and considering regional restrictions, an expert group will be
      able to plan a practical and feasible preventive strategy.

PMID- 22375213
TI  - Effects of pilates training on lumbo-pelvic stability and flexibility.
AB  - PURPOSE: This study was performed to assess and compare the effects of Pilates
      exercise on flexibility and lumbo-pelvic movement control between the Pilates
      training and control groups. METHODS: A randomized single-blinded controlled
      design was utilized in the study. Forty healthy male and female volunteers (mean
      age 31.65+/-6.21 years) were randomly divided into Pilates-based training (20
      subjects) and the control groups (20 subjects). The Pilates group attended 45
      minute training sessions, 2 times per week, for a period of 8 weeks. Flexibility
      and lumbo-pelvic stability tests were determined as outcome measures using a
      standard "sit and reach test" and "pressure biofeedback" respectively at 0, 4 and
      8 weeks of the study. RESULTS: The results showed that the Pilates training group
      improved flexibility significantly (P<0.001) during time intervals. This effect
      was also significantly greater than the control group for both 4 weeks and 8
      weeks of the training period (P<0.001). There were 65% and 85% of the subjects
      from Pilates group passing the lumbo-pelvic stability test at 4 and 8 weeks of
      training periods respectively. No subjects from the control group passed the test
      at any stages. CONCLUSIONS: Pilates can be used as an adjunctive exercise program
      to improve flexibility, enhance control-mobility of trunk and pelvic segments. It
      may also prevent and attenuate the predisposition to axial musculoskeletal
      injury.

PMID- 22375214
TI  - The Relationship between Anthropometry and Split Performance in Recreational Male
      Ironman Triathletes.
AB  - PURPOSE: The aim of this study was to investigate the relation between
      anthropometric variables and total race time including split times in 184
      recreational male Ironman triathletes. METHODS: Body mass, body height, body mass
      index, lengths and circumferences of imbs, thicknesses of skin-folds, sum of skin
      fold thicknesses, and percent body fat were related to total race time including
      split times using correlation analysis and effect size. RESULTS: A large effect
      size (r>0.37) was found for the association between body mass index and time in
      the run split and between both the sum of skin-folds and percent body fat with
      total race time. A medium effect size (r=0.24-0.36) was observed in the
      association between body mass and both the split time in running and total race
      time, between body mass index and total race time, between both the
      circumferences of upper arm and thigh with split time in the run and between both
      the sum of skin-folds and percent body fat with split times in swimming, cycling
      and running. CONCLUSIONS: The results of this study showed that lower body mass,
      lower body mass index and lower body fat were associated with both a faster
      Ironman race and a faster run split; lower circumferences of upper arm and thigh
      were also related with a faster run split.

PMID- 22375215
TI  - Martial arts: time needed for training.
AB  - PURPOSE: To measure the time needed to teach a series of martial arts techniques
      to proficiency. METHODS: Fifteen volunteer subjects without any prior martial
      arts or self-defense experience were recruited. A panel of martial arts experts
      selected 21 different techniques including defensive stances, arm blocks, elbow
      strikes, palm strikes, thumbs to eyes, instep kicks and a carotid neck restraint.
      The critical elements of each technique were identified by the panel and
      incorporated into a teaching protocol, and then into a scoring system. Two black
      belt martial arts instructors directed a total of forty-five 45-minute training
      sessions. Videotaped proficiency testing was performed weekly. The videotapes
      were reviewed by the investigators to determine the proficiency levels of each
      subject for each technique. RESULTS: The techniques were rated by the average
      number of training sessions needed for an individual to develop proficiency in
      that technique. The mean number of sessions necessary to train individuals to
      proficiency ranged from 27 to 38.3. Using this system, the most difficult
      techniques seemed to be elbow strikes to the rear, striking with thumbs to the
      eyes and arm blocking. CONCLUSIONS: In this study 29 hours of training was
      necessary to train novice students to be proficient in 21 offensive and defensive
      martial arts techniques. To our knowledge, this is the first study that attempts
      to measure the learning curves involved when teaching martial arts techniques.

PMID- 22375216
TI  - Exercise Effects on Risk of Cardiovascular Disease among Iranian Women.
AB  - PURPOSE: Physical inactivity is more prevalent among women than men, varies by
      ethnic group, and becomes increasingly prevalent with age. The aim of this study
      was to examine the effects of a 12-week exercise program on the cardiovascular
      disease risk and fitness of Iranian middle aged women. METHODS: This was a
      randomized controlled trial study. Participants in the training group (n=20)
      performed treadmill running exercise at a high intensity (70-80% of maximum heart
      rate, 0% grade) for 30 min/day, 3 days/week. On the other hand, participants in
      the control group (n=20) were asked to maintain their habitual lifestyle and not
      change their activity or dietary habits. Measurements of body mass index,
      waist/hip ratio, blood pressure, total cholesterol, and lipoprotein subtractions
      were taken before program and after 12 weeks. Changes in 10-year risk scores for
      coronary heart disease were calculated using Framingham risk equation. RESULTS:
      Significant decreases in systolic and diastolic blood pressure, reduction in 10
      year risk of coronary heart disease, and reduction in lipid levels were found
      within the training group between baseline and 12-week measurements. No changes
      were found in these parameters within the control group. CONCLUSIONS: The study
      provides evidence for the positive effects of exercise training on the reduction
      of cardiovascular disease risks among women aged 40-55 years.

PMID- 22375217
TI  - Lipocalin-2: Response to a Progressive Treadmill Protocol in Obese and Normal
      weight Men.
AB  - PURPOSE: Lipocalin-2 (Lcn2), a newer adipocyte-secreted acute phase protein, was
      recently reported to be correlated with potential effects on obesity and
      inflammation. The reaction of this protein to progressive exercise has not been
      evaluated yet. This study was designed to compare the serum Lcn2 and high
      sensitivity C-reactive protein (hs-CRP) levels after participating in an acute
      bout of treadmill protocol in obese and normal-weight men. METHODS: NINE OBESE
      (AGED: 43.2+/-4.6 yrs and body mass index (BMI): 31.4+/-1.6 kg/m(2)) and 9 normal
      weight (aged: 42.9+/-4.4 yrs and BMI: 23.03+/-1.7 kg/m(2); mean +/- SD) sedentary
      men selected randomly from volunteers performed a single bout of exercise
      according to the treadmill Bruce protocol. RESULTS: Before the exercise, Lcn2
      level was higher in obese than normal-weight individuals (P<0.05). A significant
      increase in Lcn2, hs-CRP, white blood cells (WBC) and insulin resistance index
      was observed after the exercise in both groups (P<0.05). The level of Lcn2, hs
      CRP and WBC increase was more significant in obese individuals than normal-weight
      subjects after the exercise (P<0.05). CONCLUSIONS: It seems that the levels of
      Lcn2 and other inflammatory markers elevated in obese and normal-weight men after
      participating in an exhaustive progressive exercise. These changes in obese men
      were considerable.

PMID- 22375218
TI  - Effects of selected exercises on elementary school third grade girl students'
      motor development.
AB  - PURPOSE: The aim of this study was to examine the influence of selected exercises
      on motor development in elementary school third grade girl students in Ahwaz
      City, Iran. METHODS: The present study was semi-experimental, performed as field
      and using experimental and control groups. The statistical population included
      all third grade girl students of elementary schools of Ahvaz city (10,500
      subjects). Forty of whom were randomly selected (cluster stage) and then were
      divided randomly into two experimental (N=20, Mean age=8.9+/-0.49) and control
      (N=20, Mean age=8.9+/-0.48) groups. Experimental group was given training for
      eight weeks, 3 sessions per week and each session lasting 45 minutes. To measure
      motor development, the Test of Gross Motor Development, edition2 (TGMD-2; 2002)
      was applied. Statistical analysis was performed using independent t-test and
      paired t-test. RESULTS: The results showed statistically significant differences
      between control and experimental groups regarding locomotion skills (8.433,
      P<0.05), manipulation skills (10.951, P<0.001) and overall motor development
      (13.203, P<0.001). In fact, selected exercises impacted on the motor development
      of subjects and led to their motor development progress. CONCLUSIONS: The
      selected exercises can be used as an appropriate plan to improve motor skill
      development in third grade of elementary school.

PMID- 22375219
TI  - Sarcoidosis in an athlete.
AB  - BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown
      etiology, characterized by "noncaseating granulomas" in different organs.
      Clinical signs are variable and dependent on the organ involved. Although it is
      often asymptomatic in athletes, considering the high level of athletic
      performance and the related risks due to the potential heart involvement, a
      particular diagnostic flow-chart to consider some other diagnoses is required.
      The present case report aimed to focus on the clinical approach in case of a
      progressive weakness associated with a reduction in global performance of an
      athlete. CASE PRESENTATION: Since October 2008 a 33-year-old Scandinavian
      professional soccer player has shown splitting headache, fever and impaired
      exercise tolerance. Despite some clinical aspects and symptoms that could address
      diagnosis of granulomatosis according to the current guidelines, the first
      hypothesis was indicative of a possible viral infection. Therefore, the athlete
      had received a drug-therapy resolving the headache and fever. However, because of
      the persisting weakness, several other clinical possibilities were evaluated
      following a more complete diagnostic flow-chart, blood and instrumental exams.
      CONCLUSION: This case report focuses on the substantial absence of symptoms
      during the granulomatosis disease, which makes the differential diagnosis to be
      often complicating. Indeed, several additional exams are required in order to
      establish the presence of "Non-evolutive sarcoidosis- stage I", for which the
      therapy is not mandatory.

PMID- 22375220
TI  - How to diagnose exercise induced asthma?
AB  - Exercise induced asthma (EIA) is a transient increase in airway resistance after
      intensive exercise and can be measured as a decline in forced expiratory volume
      in one second (FEV1). The condition is due to increased training load and
      inhalation of cold and dry air. Several studies have shown that eucapnic
      voluntary hyperpnea challenge test (EVH test) is a very sensitive and specific
      diagnostic method. EVH test develops EIA by hyperventilation of dry gas and the
      test achieves the same airway obstruction as training in cold and dry air. The
      test is better than the previously used methacholine challenge test.

PMID- 22375221
TI  - Diagnostic value of bioelectrical impedance analysis versus body mass index for
      detection of obesity among students.
AB  - PURPOSE: Obesity is a common nutritional problem in both developed and developing
      countries. The aim of this study was to determine the prevalence of
      overweightness and obesity using both bioelectrical impedance analysis (BIA) and
      body mass index (BMI). METHODS: In this cross-sectional study, 288 healthy
      college students were selected. Socio-economic status questionnaires were
      completed and subjects' anthropometric features were measured by a trained nurse.
      BMI was calculated and body fat mass (BFM) and body fat percent (BF%) were
      obtained using BIA method by hand-to-hand Omron BF-500 set. RESULTS: Mean age of
      the subjects was 21.1+/-1.7 years. Based on BMI, 2.6% of males and 2.2% of
      females were obese while 15.7% and 9.6% were diagnosed to be overweight
      respectively. The correlation between BMI values and BFM were 0.883 and 0.908 in
      males and females respectively (P<0.001). Furthermore, BF% had a significant
      correlation with BMI in both males and females (P<0.001). CONCLUSION: Our survey
      demonstrated a lower prevalence of obesity and overweightness in college students
      compared with Iranian general population, especially in females. Additionally,
      BIA method was shown to be closely correlated with and as much valuable as BMI in
      regard to detection of obesity.

PMID- 22375222
TI  - Physique and body composition in soccer players across adolescence.
AB  - PURPOSE: Although the contribution of physique and body composition in soccer
      performance was recognized, these parameters of physical fitness were not well
      studied in adolescent players. Aim of this study was to investigate physique and
      body composition across adolescence. METHODS: Male adolescents (N=297 aged 12.01
      20.98 y), classified into nine one-year age-groups, child (control group, N=16
      aged 7.34-11.97 y) and adult players (control group, N=29 aged 21.01-31.59 y),
      all members of competitive soccer clubs, performed a series of anthropometric
      measures (body mass, height, skinfolds, circumferences and girths), from which
      body mass index (BMI), percentage of body fat (BF%), fat mass (FM), fat free mass
      (FFM) and somatotype (Heath-Carter method) were calculated. RESULTS: Age had a
      positive association with FM (r=0.2, P<0.001) and FFM (r=0.68, P<0.001), and a
      negative association with BF (r=-0.12, P=0.047). Somatotype components changed
      across adolescence as well; age was linked to endomorphy (r=-0.17, P=0.005),
      mesomorphy (r=0.14, P=0.019) and ectomorphy (r=-0.17, P=0.004). Compared with age
      matched general population, participants exhibited equal body mass, higher
      stature, lower body mass index and lower BF. CONCLUSION: During adolescence,
      soccer players presented significant differences in terms of body composition and
      physique. Thus, these findings could be employed by coaches and fitness trainers
      engaged in soccer training in the context of physical fitness assessment and
      talent identification.

PMID- 22375223
TI  - Effects of aerobic exercise and whole body vibration on glycaemia control in type
      2 diabetic males.
AB  - PURPOSE: Aerobic exercise has been identified as the main treatment for type 2
      diabetic patients. Such an exercise, however, is usually repined by some of
      patients who suffer from lack of stamina. Therefore, whole body vibration has
      recently been introduced as a passive intervention. The present study aimed at
      comparing how aerobic exercise and whole body vibration affect glycaemia control
      in type 2 diabetic males. METHODS: Thirty diabetic males were divided into three
      groups, namely aerobic exercise (AE), whole body vibration (WBV), and control.
      Aerobic exercise schedule consisted of three walking sessions a week, each for 30
      60 minutes and in 60-70% of maximum stock heartbeat. Vibration exercise was
      composed of 8-12-min stand-up and semi-squat positioning in frequency of 30 Hz
      and amplitude of 2 mm. Concentrations of fasting glycosylated hemoglobin, fasting
      glucose, and insulin were measured in the beginning of the trial, after the
      fourth week, and after the eighth week. RESULTS: After 8 weeks of exercise, no
      significant difference was detected in concentrations of fasting glycosylated
      hemoglobin and insulin between the groups (P=0.83, P=0.12). There were no
      significant differences in any of the variables between AE and WBV (P>0.05). But
      a more significant decrease in fasting glucose was observed in exercise groups
      (AE and WBV) compared with control group (P=0.02). CONCLUSION: The present study
      showed that AE and WBV identically stimulate metabolic system. Thus, it can be
      concluded that type 2 diabetic patients lacking stamina for aerobic exercise can
      opt for vibration exercise as an effective substitute.

PMID- 22375224
TI  - The effect of cryotherapy on the normal ankle joint position sense.
AB  - PURPOSE: To determine whether a fifteen-minute water immersion treatment affects
      the normal ankle joint position sense (JPS) at the middle range of dorsiflexion
      and plantar flexion actively and passively. METHODS: Thirty healthy female
      volunteers aged between 18 and 30 years were treated by a 15-minute cryotherapy
      (6 +/- 1 degrees C). The subject's skin temperature over antromedial aspect of
      dominant ankle was measured by the Mayomed device before, immediate and 15
      minutes after water immersion. Ankle JPS was tested trough the pedal goniometer
      at 3 stages similar to the skin temperature. ANOVA (alpha = 0.05) was performed
      on each of variables using SPSS 19.0 software. RESULTS: Skin temperature was seen
      to decrease after water immersion but subjects did not return to pre-test skin
      temperature after 15 minutes (P<0.001). The research found no significant
      difference in JPS at middle range of dorsiflexion and plantar flexion actively
      and passively before and after cryotherapy. CONCLUSION: These findings suggest
      that 15-minute water immersion at 6 degrees C dose not significantly alter the
      middle range of plantar flexion/ dorsiflexion JPS at the ankle and is not
      deleterious to JPS.

PMID- 22375225
TI  - The effects of progressive muscle relaxation and autogenic relaxation on young
      soccer players' mood states.
AB  - PURPOSE: This study was designed to compare the effects of two different
      relaxation techniques, namely progressive muscle relaxation (PMR) and autogenic
      relaxation (AGR) on moods of young soccer players. METHODS: sixteen adolescent
      athletes (mean age: 14.1 +/- 1.3) received either PMR or AGR training. Using
      Profile of Mood States- Adolescents, their mood states were measured one week
      before relaxation training, before the first relaxation session, and after the
      twelfth relaxation session. RESULTS: Mixed ANOVA revealed no significant
      interaction effects and no significant main effects in any of the subscales.
      However, significant main effects for testing sessions were found for confusion,
      depression, fatigue, and tension subscales. Post hoc tests revealed post
      intervention reductions in the confusion, depression, fatigue, and tension
      subscale scores. CONCLUSION: These two relaxation techniques induce equivalent
      mood responses and may be used to regulate young soccer players' mood states.

PMID- 22375226
TI  - The Persian, last 7-day, long form of the International Physical Activity
      Questionnaire: translation and validation study.
AB  - PURPOSE: To translate long form, interview-administered International Physical
      Activity Questionnaire (IPAQ) from English to Persian and evaluate its validity,
      reliability and reproducibility. METHODS: A forward-backward translation
      procedure was followed to develop the Persian version of the IPAQ. A total of 218
      respondents (53.7% women, aged 22-76 yr) completed the Persian version in Tehran,
      Iran. To examine the test-retest reliability, 48 healthy volunteers completed the
      IPAQ twice during a 7-day period.. The PA indicators derived from the IPAQ were
      assessed for reliability and were compared with aerobic fitness and body mass
      index (BMI) for construct validity. RESULTS: In general, the questionnaire was
      received well and all domains met the minimum reliability standards (intra-class
      correlation [ICC]>0.7), except for Leisure-time physical activity (PA). Aerobic
      fitness showed a weak positive correlation with all of the PA results derived
      from the IPAQ. A significant correlation was observed between the IPAQ data for
      total PA and both aerobic fitness (r=0.33, P<0.001) and BMI (r=0.26, P<0.001).
      Performing a known group comparison analysis, the results indicated that the
      questionnaire was discriminated well between the subgroups of the study samples
      expected to be different in their physical activity. CONCLUSIONS: The Persian
      version of the long form, interview-administered IPAQ had an acceptable
      reliability and validity for assessing total PA in our Iranian sample of
      individuals. It may be a useful instrument for generating internationally
      comparable data on PA.

PMID- 22375227
TI  - Sudden cardiac death in athletes: is universal ECG screening plausible?

PMID- 22375228
TI  - Sudden cardiac death in young athletes.

PMID- 22375229
TI  - Author's reply to pgs. 117-9, 120-2.

PMID- 22375230
TI  - The Student Committee of Sports Medicine Research Center: to be independent or
      not to be? That is the question.

PMID- 22375231
TI  - Ramadan and Its Effect on Fuel Selection during Exercise and Following Exercise
      Training.
AB  - Fasting induces short-term physiological adaptations which spare the body's
      remaining carbohydrate stores and mobilize lipid stores to provide a substitute
      fuel for many tissues and organs, especially skeletal muscle. Rodent studies show
      that regular occurrence of fasting then refeeding, stimulates adaptations in
      muscle which make the animal better placed to withstand a further period of
      fasting by possessing a better ability to oxidise lipid.This review explores the
      research describing these adaptations, with an emphasis on Ramadan, a human model
      of repeated fasting/refeeding. Separately, a single bout of endurance exercise
      places similar metabolic stress on the body as fasting since the exercising
      muscle must reduce its use of carbohydrate and utilize lipid more readily as
      exercise progresses. Not surprisingly therefore, adaptations in muscle to
      repeated bouts of endurance exercise (endurance training) are similar to those
      seen with repeated fasting/refeeding. Superimposing the stressors of repeated
      fasting/refeeding and exercise training, and subsequent adaptations to the muscle
      and exercise response, are examined by describing the published research which
      has investigated the situation where athletes continue their training whilst
      participating in Ramadan.

PMID- 22375232
TI  - Effects of ramadan fasting on biochemical and anthropometric parameters in
      physically active men.
AB  - PURPOSE: The aim of this study was to assess the effects of Ramadan fasting on
      several biochemical and anthropometric parameters in physically active men by
      comparing fasters and nonfasters before, during, and after Ramadan. METHODS:
      Eighteen physically active men (10 fasters and 8 nonfasters) participated in this
      study. Subjects visited the laboratory for a total of four sessions on the
      following occasions: three days before Ramadan (Bef-R), the 15(th) day of Ramadan
      (Mid-R), the 29(th) day of Ramadan (End-R), and 21 days after Ramadan (Post-R).
      During each session, subjects underwent anthropometric measurements, completed a
      dietary questionnaire and provided a fasting blood sample. RESULTS: Body weight
      and body fat percentage decreased in fasters by 1.9% (P<0.001) and 6.2%
      (P=0.003), respectively, but increased in nonfasters by 2.2% (P<0.001) and 10.2%
      (P=0.001), respectively, from Bef-R to End-R. Fasters' hematocrit and hemoglobin
      increased by 5.3% (P<0.001) and 6.3% (P=0.01), respectively, from Bef-R to End-R,
      while neither of these parameters changed in nonfasters. Fasters experienced an
      increase in the following parameters from Bef-R to End-R: urea (8.7%; P<0.001),
      creatinine (7.5%; P<0.001), uric acid (12.7%; P<0.001), serum sodium (1.9%;
      P<0.001), serum chloride (2.6%; P<0.001) and high-density lipoprotein cholesterol
      (27.3%; P<0.001). Of these parameters, only creatinine increased (4.4%; P=0.01)
      in nonfasters. CONCLUSION: We conclude that Ramadan fasting lowers body weight
      and body fat percentage and can elevate high-density lipoprotein cholesterol in
      physically active men. However, practicing aerobic exercise during a hot and
      humid Ramadan month can induce a state of dehydration marked by an increase in
      some renal function markers and serum electrolytes.

PMID- 22375233
TI  - Effects of fasting during ramadan month on cognitive function in muslim athletes.
AB  - PURPOSE: Our study aimed to profile the effect of fasting during the Ramadan
      month on cognitive function in a group of healthy Muslim athletes. METHODS:
      Eighteen male athletes underwent computerized neuropsychological testing during
      (fasting) and after (non-fasting) Ramadan. Diet was standardized, and tests were
      performed at 0900h and 1600h to characterize potential time-of-day (TOD)
      interactions. Psychomotor function (processing speed), vigilance (visual
      attention), visual learning and memory, working memory (executive function),
      verbal learning and memory were examined. Capillary glucose, body temperature,
      urine specific gravity, and sleep volume were also recorded. RESULTS: Fasting
      effects were observed for psychomotor function (Cohen's d=1.3, P=0.01) and
      vigilance (d=0.6, P=0.004), with improved performance at 0900h during fasting;
      verbal learning and memory was poorer at 1600h (d=-0.8, P=0.03). A TOD effect was
      present for psychomotor function (d=-0.4, P<0.001), visual learning (d=-0.5,
      P=0.04), verbal learning and memory (d=-1.3, P=0.001), with poorer performances
      at 1600h. There was no significant fasting effect on visual learning and working
      memory. CONCLUSIONS: Our results show that the effect of fasting on cognition is
      heterogeneous and domain-specific. Performance in functions requiring sustained
      rapid responses was better in the morning, declining in the late afternoon,
      whereas performance in non-speed dependent accuracy measures was more resilient.

PMID- 22375234
TI  - Effect of Acute Maximal Exercise on Circulating Levels of Interleukin-12 during
      Ramadan Fasting.
AB  - PURPOSE: The purpose of this study was to examine the effects of Ramadan fasting
      on circulating levels of interleukin-12 (IL-12) after a brief maximal exercise.
      METHODS: NINE SUBJECTS PERFORMED A WINGATE TEST ON THREE DIFFERENT OCCASIONS: (i)
      the first week of Ramadan (1WR), (ii) the fourth week of Ramadan (4WR), and (iii)
      three weeks after Ramadan (AR). Blood samples were taken before, immediately and
      60 min after the exercise. Plasma concentrations of IL-12 were measured using
      enzyme-linked immunosorbent assay. Variance analysis revealed no significant
      effect of Ramadan on P(peak) and P(mean) during the three testing periods.
      RESULTS: Considering the effect of Ramadan on plasma concentrations of IL-12,
      analysis of the variance revealed a significant Ramadan effect (F((2,)
      (16))=66.27; P < 0.001) as well as a significant time effect (F((2,) (16))=
      120.66; P < 0.001). However, no significant (Ramadan * time) of test interaction
      (F((4,) (32))=2.40; P>0.05). For all measures, IL-12 levels were lower during 1WR
      and 4WR in comparison with AR (P < 0.05). Considering the exercise effects, IL-12
      levels measured immediately after the exercise were significantly higher than
      those measured before and at 60 minutes after the exercise (P < 0.001).
      CONCLUSIONS: These results suggest that an acute intense exercise-induced IL-12
      response is modified by daytime fasting and modifications in sleep schedule
      during Ramadan.

PMID- 22375235
TI  - Effect of ramadan fasting on body composition and physical performance in female
      athletes.
AB  - PURPOSE: The aim of this study was to determine the effect of Ramadan fasting on
      body composition, calorie intake and physical performance in young female
      athletes undertaking training sessions during Ramadan. METHODS: Twelve voluntary
      female athletes (15-27 years old) were assigned to the research. A prospective
      study was conducted to investigate the athletes on four different occasions: one
      week before Ramadan (T1), the second (T2) and fourth (T3) weeks of Ramadan, and
      two weeks after the end of Ramadan (T4). Food intake, body composition and
      physical performance (agility, balance and explosive leg power) were investigated
      on each occasion. Further, Physical performance was assessed by agility, vertical
      jump and balance tests. RESULTS: There was a significant main effect for time for
      body composition indices. A significant decrease was observed in weight (P=0.01)
      and body mass index (BMI) (P=0.01) in T2 compared with T1, further decrease in
      weight (P<0.001) and BMI (P<0.001) was observed in T3 compared to T1. Calorie
      intake decreased significantly in T3 compared with T1 (P=0.008), and increased
      significantly in T4 compared with T3 (P=0.04). There was a significant main
      effect for time for agility performance (P=0.03), but no significant main effect
      for time was observed for vertical jumping (P=0.1) and balance performance
      (P=0.3). CONCLUSIONS: This study has found that Ramadan fasting could affect the
      body composition, but not physical performance in female athletes during Ramadan.

PMID- 22375236
TI  - Subjective Perception of Sports Performance, Training, Sleep and Dietary Patterns
      of Malaysian Junior Muslim Athletes during Ramadan Intermittent Fasting.
AB  - PURPOSE: To examine the subjective perception of daily acute fasting on sports
      performance, training, sleep and dietary patterns of Muslim athletes during the
      Ramadan month. METHODS: Seven hundred and thirty-four (411 male and 323 female)
      Malaysian Junior-level Muslim athletes (mean age 16.3 +/- 2.6 y) participated in
      the survey which was designed to establish the personal perception of their sport
      performance, sleep pattern, food and fluid intake during Ramadan fasting. The
      survey was conducted during and immediately after the month of Ramadan in 2009.
      RESULTS: Twenty-four percent of the athletes perceived that there was an adverse
      effect of the Ramadan fast on their sporting performance and 29.3% reported that
      quality of training during Ramadan was also negatively influenced. Majority
      (48.2%) of the athletes stated that Ramadan fasting did not affect their normal
      sleep pattern but 66.6% of them complained of sleepiness during the daytime. Half
      of the athletes (41.4%) maintained the caloric intake during Ramadan as they
      normally would with the majority of them (76.2%) reporting that they consumed
      more fluids during Ramadan. CONCLUSIONS: Overall, Malaysian Junior-level Muslim
      athletes showed diverse views in their perception of changes in their training,
      sleep and dietary patterns during Ramadan fast. These individual differences
      probably indicate differences in the athletes' adaptability and coping strategies
      during fasting and training in Ramadan.

PMID- 22375237
TI  - The effect of ramadan fasting on physical performances, mood state and perceived
      exertion in young footballers.
AB  - PURPOSE: This study was designed to assess the effects of Ramadan fasting on the
      profile of mood state and perceived exertion in young soccer players and aerobic
      and anaerobic performances during the Yo-Yo, repeated sprint ability (RSA) and
      the Wingate tests. METHODS: Twenty junior male soccer players completed the Yo
      Yo, the RSA, and the Wingate tests on three different occasions: one-week before
      Ramadan (BR), the second week (SWR) and the fourth week (ER) of Ramadan. The
      total distance (TD) covered and the estimated maximal aerobic velocity (MAV)
      during the Yo-Yo test were recorded. During the RSA test, peak power (PP) during
      each sprint, the percentage of decrement of PP (PD) and total work (Wtotal) were
      calculated. During the Wingate test, peak (P(peak)) and mean (P(mean)) powers and
      fatigue index (FI) were recorded. RESULTS: TD and MAV (P=0.01) during the Yo-Yo
      test and PP (P=0.01, P=0.004, P=0.001, P=0.01, P=0.03 for sprints 1, 2, 3, 4, and
      5, respectively) and Wtotal (P=0.02) during the RSA test were significantly
      higher during BR than ER. Furthermore, muscle fatigue during the RSA test
      increased significantly from BR to ER (P=0.01). P(peak) and P(mean) during the
      Wingate test decreased significantly from BR to SWR and ER (P<0.0005). FI was
      higher during SWR (P=0.001) and ER (P<0.0005) than BR. In addition, rating of
      perceived exertion scores and fatigue estimated by the profile of mood state
      questionnaire were higher during Ramadan in comparison with BR. CONCLUSIONS: The
      present study suggests that both aerobic and anaerobic performances during the Yo
      Yo, the RSA and the Wingate tests were affected by Ramadan fasting in young
      soccer players.

PMID- 22375238
TI  - Effect of ramadan fasting on body water status markers after a rugby sevens
      match.
AB  - PURPOSE: To evaluate the effect of Ramadan fasting on body water status markers
      of rugby players at basal condition and following a simulation of rugby sevens
      match. METHODS: TWELVE RECREATIONAL RUGBY SEVENS PLAYERS PLAYED THREE MATCHES:
      one day before Ramadan (before Ramadan), at the end of the first week of Ramadan
      (Beg-R) and at the end of Ramadan (End-R). Before and immediately after each
      match, body weight was determined and blood samples were taken for the
      measurement of body water status markers. Total body water was measured with an
      impedancemeter only before matches. RESULTS: At rest, an increase in hematocrit
      (+4.4%, P=0.03), hemoglobin (+3.4%, P=0.01) and plasma osmolarity (+2.8%,
      P<0.001) was noticed at End-R compared to before Ramadan. Total body water
      measured before Ramadan did not differ significantly from that of Ramadan. After
      the match, values of hematocrit and plasma osmolarity increased significantly at
      End-R (+1.4%, P=0.02; +3.1%, P<0.001 respectively) compared to before Ramadan.
      Although, hemoglobin measured after matches occurring during Ramadan did not
      differ from those of before Ramadan. In response to matches, the change of
      percentage of body water status markers did not differ during each period of the
      investigation. CONCLUSIONS: The present results show that Ramadan fasting induces
      dehydration at basal conditions. Also, rugby sevens match played during Ramadan
      did not exacerbate the magnitude of responses to matches of blood and body water
      status markers.

PMID- 22375239
TI  - Temporal Patterns of Subjective Experiences and Self-Regulation during Ramadan
      Fasting among Elite Archers: A Qualitative Analysis.
AB  - PURPOSE: Some major competitions (e.g. London Olympics, 2012) are scheduled
      during the Ramadan fasting month. Little attention has been given to explore the
      archers' performance related subjective experiences with a qualitative method.
      Therefore, this study addressed individual archers' subjective experiences within
      the framework of self-regulation during Ramadan. METHODS: Eleven elite Malaysian
      Muslim fasting archers volunteered to participate in the study. Grounded theory
      was the qualitative approach used to examine the subjective experiences of
      athletes during Ramadan. Interviews were conducted and inductive content analysis
      was adopted to identify the temporal patterns of self-regulation of subjective
      experiences across the fasting period. RESULTS: Inductive content analysis
      identified (a) physical, (b) mental,(c) emotional, (d) behavioral, and (e)
      spiritual experiences. Overall patterns revealed that experiences associated with
      physical, emotional, behavioral, and spiritual dimensions dominated in the first
      phase of fasting, while the mental dimension surfaced increasingly in the latter
      phase of fasting. CONCLUSIONS: The trend showed changes in the patterns of
      experiences among the major domains across the temporal dimension. Athletes
      reported increased subjective experiences in mental factors toward the latter
      half of the fasting period. Practitioners should emphasize on mental aspects of
      training, as these appear to be salient in archery performance.

PMID- 22375240
TI  - Investigating Two Different Training Time Frames during Ramadan Fasting.
AB  - PURPOSE: Muslim athletes may continue training and competing while they are
      fasting. There is a concern about negative effects of fasting on sports
      performance. This study aimed to investigate the influence of two training time
      frames on athletes' body composition and performance during Ramadan fasting.
      METHODS: An observational study was conducted and thirty four male volunteer
      athletes from different sports including volleyball, karate, taekwondo and
      football were assigned in two groups. The first group included 14 elite athletes
      who during Ramadan voluntarily participated in training sessions at 1 hour before
      Iftar (BI) and the second group of 20 elite athletes who during Ramadan
      participated in training sessions at 3 hours after Iftar (AI). Testing was
      performed one week before; in the first and fourth weeks of Ramadan and one week
      after Ramadan. Weights, heights and skinfold thickness were assessed at each time
      point and body mass index was calculated. Each player was assessed for agility
      and explosive strength as well. RESULTS: The mean weight and body mass index of
      both groups decreased significantly during Ramadan (P<0.001). Performance
      variables were not negatively affected by fasting in BI or AI group athletes.
      CONCLUSIONS: Weight reduction might come with either BI or AI training schedules
      in Ramadan. Daytime or evening training did not inversely affect the agility and
      power performances in a group of elite athletes during Ramadan fasting.

PMID- 22375242
TI  - Correlations of Handgrip Strength with Selected Hand-Arm-Anthropometric Variables
      in Indian Inter-university Female Volleyball Players.
AB  - PURPOSE: The purpose of this study was to estimate the dominant handgrip strength
      and its correlations with some hand and arm anthropometric variables in 101
      randomly selected Indian inter-university female volleyball players aged 18-25
      years (mean age 20.52+/-1.40) from six Indian universities. METHODS: Three
      anthropometric variables, i.e. height, weight, BMI, two hand anthropometric
      variables, viz. right and left hand width and length, four arm anthropometric
      variables, i.e. upper arm length, lower arm length, upper extremity length, upper
      arm circumference and dominant right and non-dominant handgrip strength were
      measured among Indian inter-university female volleyball players by standard
      anthropometric techniques. RESULTS: The findings of the present study indicated
      that Indian female volleyball players had higher mean values in eleven variables
      and lesser mean values in two variables than their control counterparts, showing
      significant differences (P<0.032-0.001) in height (t=2.63), weight (t=8.66), left
      hand width (t=2.10), left and right hand length (t=9.99 and 10.40 respectively),
      right upper arm length (t=8.48), right forearm length (t=5.41), dominant (right)
      and non-dominant (left) handgrip strength (t=9.37 and 6.76 respectively). In
      female volleyball players, dominant handgrip strength had significantly positive
      correlations (P=0.01) with all the variables studied. CONCLUSION: It may be
      concluded that dominant handgrip strength had strong positive correlations with
      all the variables studied in Indian inter-university female volleyball players.

PMID- 22375241
TI  - Vitamin d and athletic performance: the potential role of muscle.
AB  - Vitamin D deficiency is a worldwide epidemic, with well known impacts on calcium
      metabolism and bone health, but increasingly recognized associations with chronic
      health problems such as bowel and colonic cancer, arthritis, diabetes and
      cardiovascular disease. In recent years in the Sports Medicine literature, there
      has been an increased focus on the potential impact that inadequate Vitamin D
      levels may have on athletic performance.In the early 20(th) Century, athletes and
      coaches felt that ultraviolet rays had a positive impact on athletic performance,
      and while remaining limited, evidence is accumulating to support this view.
      Muscle structure and function is recognised to play a key role in athletic
      performance, and both cross-sectional and longitudinal studies allude to a
      functional role for Vitamin D in muscle. The identification of the Vitamin D
      receptor in muscle tissue provides a direct pathway for Vitamin D to impact upon
      Skeletal Muscle structure and function. This review focuses on the current
      understanding of the action of Vitamin D within skeletal muscle tissue, and the
      potential impact on performance.

PMID- 22375243
TI  - Effect of eccentric isotonic quadriceps muscle exercises on patellofemoral pain
      syndrome: an exploratory pilot study.
AB  - PURPOSE: There is a decrease in quadriceps muscle strength in subjects with
      patellofemoral pain syndrome. Various types of strengthening exercises of the
      quadriceps are done as part of its management, but the effect of isotonic
      eccentric quadriceps muscle exercises on patellofemoral pain syndrome has not
      been studied. Hence the aim of this exploratory pilot study was to evaluate the
      effect of eccentric quadriceps training in patients with patellofemoral pain.
      METHODS: Twenty patients (12 female and 8 male, mean ages, 27.50 +/- 6.6 years)
      with patellofemoral pain syndrome were treated. The eccentric training of the
      quadriceps was given using a Baltimore Therapeutic Equipment (BTE) Primus
      machine. The main outcome measures used were percentage time on target as shown
      by the BTE primus machine, SF-36 Health questionnaire and patellofemoral pain
      severity scale. Statistical analysis was performed using SPSS 13. RESULTS: All
      the outcome measures showed significant improvements (P<0.05). Percentage time on
      target improved with a mean difference of 23.6, the SF-36 questionnaire showed an
      improvement in physical component score, mental component score and bodily pain
      with a mean difference of 10.9, 2.6 and 29.2 respectively and pain score when
      taken using patellofemoral severity scale also improved with a mean difference of
      3.4. CONCLUSION: Isotonic eccentric training of quadriceps muscles was found to
      be effective in reducing pain and improving the functional status of patients
      with patellofemoral pain syndrome and can be suggested as part of the treatment.

PMID- 22375244
TI  - The attenuation of strike acceleration with the use of safety equipment in tae
      kwon do.
AB  - PURPOSE: THE OBJECTIVES OF THIS STUDY INCLUDE: (1) Determination of the
      attenuation of strike acceleration that Tae Kwon Do sparring safety pads provide
      from kicks from Olympic style TKD fighters, (2) The sex and weight
      differentiation in acceleration achieved within the thorax model with the
      roundhouse kicks. METHODS: This prospective, observational study utilized 15
      Olympic style fighters from an "elite" team kicking a water core heavy bag thorax
      model with roundhouse kicks. The model was fitted with a tri-axial accelerometer
      (GCDC, model X250-2) to measure g acceleration from strikes to the bag. The bag
      was kicked in three, 10 kick phases by all subjects: kicks without padding; kicks
      with hogu on heavy bag, and kicks with hogu and instep guards on feet. The g
      acceleration readings were recorded in all phases. RESULTS: Kolmogorov-Smirnov
      failed for all variables. There were 8 female subjects: median age 14 years,
      median weight 53.4 kg and 7 male subjects: median age 17 years, median weight
      70.45 kg. The ANOVA on ranks of the acceleration from kicks against the bag
      achieved significance, P=0.001. Spearman rank order correlation between the
      weights of players and acceleration of strike against the hogu without and with
      insteps pads was significant, P=0.035/r=0.54 and P=0.018/r=0.59, respectively.
      CONCLUSION: Heavier and male subjects tend to produce more force in strikes.
      Protective chest guard reduces acceleration to the thorax model, but the utility
      of instep guards is questionable.

PMID- 22375245
TI  - The offensive efficiency of the high-level handball players of the front and the
      rear lines.
AB  - PURPOSE: The aim of this study was to investigat the offensive efficiency of the
      professional handball players forming the front and rear lines. METHODS: Our
      investigation was carried out on four matches (final, semi-finals and classifying
      match) at the 19(th) male Handball World Championship "Tunisia 2005". Finalist
      teams were Tunisia, France, Croatia, and Spain. Matches were recorded using 5
      digital camcorders (SONY, DCL, and TRV 130E). Number of passes and the length of
      the attacks were determined by software "STUDIO 9". Speed of the ball at the
      different shootings was calculated by REGAVI software, version 2.57, 2004. Work
      was dissociated according to 2 variables namely axes and lines. RESULTS: Players
      of lateral axes (A4) and front basis (L1) were shorter and thinner than those of
      the central axis (A3) and rear basis (L2). No differences were observed between
      lines and axes in age. The analysis of the total shootings to the goal shows that
      the players of lines and axes present very close values in each team, excepting
      the Croatian L2 compared to the Tunisian L2. Players of the rear Croatian basis
      present also a number of attacks concluded by a non-successfully cadred shooting
      greater than all other groups. In the Spanish group, a significant difference
      among number of passes concluded by a non-successfully cadred shooting between
      lines, and front basis vs central axis was noted. No significant difference was
      found between lines and axes in the Croatian team. Regarding the velocity of
      shooting, excepting the Croatian team, no differences were found between lines
      and axes of the other teams. No differences were also noted in the attack
      duration between lines and axes in Croatian and Tunisian teams. In the Spanish
      team, duration of attacks concluded by a cadred shooting was most important when
      finished by an L2 or an A3 player. CONCLUSION: The present results demonstrate
      that finalist teams were found to be clearly characterized by L2 and A3 players
      taller and weightier than those of L1 and A4. Organized attack was generally
      concluded by shooting done by an L2 or an A4 player and the shooting velocity did
      not significantly determine the offensive efficiency.

PMID- 22375246
TI  - Functional performance testing in athletes with functional ankle instability.
AB  - PURPOSE: To determine if functional performance deficits are present in athletes
      with functional ankle instability (FAI) compared to healthy athletes using
      various functional performance tests. METHODS: Sixty two athletes (mean age
      21.7+/-1.8years; height-168.2+/-9.1cm; weight-63.8+/-11.0kg) participated in this
      case control study. Athletes were divided into two groups: athletes with FAI (FAI
      group, n=31) and healthy athletes (Non-FAI group, n=31). The FAI group was
      further divided into two subgroups: FAI with giving way (FAI-GW), FAI with no
      giving way (FAI-NGW). Functional performance was assessed with the single-limb
      hopping test, figure-of-8 hop test, side-hop test, single-limb hurdle test,
      square hop test and single hop test. RESULTS: Significant differences (P<0.05)
      were observed for all the functional performance tests (FPTs) except the single
      hop test between FAI and Non-FAI groups; between FAI-GW, FAI-NGW and Non-FAI
      groups. Additionally, the involved limb performed significantly worse (P<0.05)
      than the contra-lateral uninvolved limb of the FAI-GW group for the above
      mentioned FPTs. CONCLUSION: Significant functional performance deficits were
      observed in the FAI group in all tests except single hop test with greater
      deficits observed in the FAI-GW group. Hence, these tests can be used to
      determine the presence of FAI. However no deficits were identified for the test
      involving sagittal plane functional activities suggesting that this test can not
      be used as a criterion to discriminate individuals with FAI. It was further
      ascertained that functional performance was not affected by limb dominance.

PMID- 22375247
TI  - How effective is sun salutation in improving muscle strength, general body
      endurance and body composition?
AB  - PURPOSE: The purpose of the present study was to evaluate effects of regular
      practice of sun salutation on muscle strength, general body endurance and body
      composition. METHODS: Subjects (49 male and 30 female) performed 24 cycles of sun
      salutation, 6 days a week for 24 weeks. Upper body muscle strength was determined
      by 1 repetition maximum (1RM) for bench press and shoulder press technique. Back
      and leg dynamometry was used to assess strength of back and leg muscles. General
      body endurance was evaluated by push-up and sit-up tests. Body composition was
      assessed by noting% body fat by using bioelectric impedance analysis. Perceived
      intensity of exercise by subjects was noted by Borg scale. RESULTS: Muscle
      strength by bench press showed significant increase in male (29.49+/-9.70 to
      36.12+/-9.09 Kg, P<0.001) and female (10.5+/-4.42 to 13.16+/-4.44 Kg, P<0.001)
      subjects. Strength by shoulder press also increased (males; 22.96+/-9.57 Kg to
      26.53+/-11.05 Kg, P<0.001, females; 6.83+/-2.78 to 8.83+/-3.87, P<0.001).
      Endurance by push-ups & sit-ups showed similar findings in male (19.0+/-9.58 to
      21.98+/-8.98, P<0.001 and 24.92+/-10.41 to 29.84+/-12.64, P<0.001 respectively)
      and female (14.66+/-6.80 to 18.56+/-6.97 and 13.16+/-7.75 to 19.23+/-8.25,
      P<0.001 respectively) subjects. A significant decrease in body fat percent was
      observed only in female (27.68+/-5.46 to 25.76+/-4.72, P<0.001) but not in male
      subjects. BMI significantly decreased in both the groups (z=4.37, P<001 and
      t=5.41, P<0.001 respectively). CONCLUSION: From our observations we conclude that
      sun salutation can be an ideal exercise to keep oneself in optimum level of
      fitness.

PMID- 22375249
TI  - Sudden cardiac death in athletes: big trouble, not so little Asia.

PMID- 22375248
TI  - A pilot trial on kinematic magnetic resonance imaging using a superconducting,
      horizontally opened, 1.2 T magnetic resonance system.
AB  - PURPOSE: This study was performed to introduce and evaluate the potential of
      kinematic magnetic resonance imaging (KMRI) using a high-field open-magnet
      magnetic resonance (MR) system. METHODS: We attempted to perform KMRI of healthy
      volunteers' lumbar spine and knee in the lateral position and ankle in the supine
      position utilizing the superconducting, horizontally opened, 1.2 T MR system
      (OASIS, HITACHI, Tokyo, Japan). For the KMRI of the lumbar spine, the volunteer
      had to lie on one side while maintaining maximally anteflexed, neutral, and
      maximally retroflexed positions and remain still for the duration of the
      acquisition time for each posture. In the same way, KMRI of the knee was
      performed with the volunteer's knee flexed at 0 degrees , 30 degrees , 60 degrees
      , 90 degrees , and 120 degrees  in the lateral position, and KMRI of the ankle
      was performed with the volunteer's ankle in maximally dorsiflexed, neutral, and
      maximally plantarflexed positions while lying in the supine position. RESULTS: We
      could acquire higher quality kinematic MR images than those acquired using low
      field MR systems. The spinal canal, intervertebral discs and foramina, and facet
      joints in lumbar spine KMRI; the ligaments, menisci and patellofemoral joint in
      knee KMRI; and the tibiotalar articulation and peroneal tendon in ankle KMRI were
      clearly depicted. CONCLUSION: The results of our pilot trial indicated that a
      superconducting horizontally opened, 1.2 T MR system offers high-quality KMRI
      images and can be utilized for the kinematic diagnosis and evaluation of sports
      injuries.

PMID- 22375250
TI  - Collision of millimetre droplets induces DNA and protein transfection into cells.
AB  - Nonperturbing and simple transfection methods are important for modern techniques
      used in biotechnology. Recently, we reported that electrospraying can be applied
      to DNA transfection in cell lines, bacteria, and chicken embryos. However, the
      transfection efficiency was only about 2%. To improve the transfection rate,
      physical properties of the sprayed droplets were studied in different variations
      of the method. We describe a highly efficient technique (30-93%) for introduction
      of materials such as DNA and protein into living cells by electrospraying
      droplets of a high conductivity liquid onto cells incubated with the material for
      transfection. Electric conductivity has a sizable influence on the success of
      transfection. In contrast, molecular weight of the transfected material, types of
      ions in the electrospray solution, and the osmotic pressure do not influence
      transfection efficiency. The physical analysis revealed that collision of cells
      with millimetre-sized droplets activates intracellular uptake.

PMID- 22375251
TI  - Eyespot colour pattern determination by serial induction in fish: Mechanistic
      convergence with butterfly eyespots.
AB  - Vertebrate and invertebrate colour pattern determination mechanisms are
      considered distinct; recently, however, both fish and butterfly colour patterns
      have been partly explained by reaction-diffusion mechanisms. Here, we show that
      multi-coloured eyespots of the spotted mandarin fish, which are reminiscent of
      butterfly eyespots, are determined by the serial induction of colour patterns.
      The morphological characterisation of eyespots indicates a sequence of colour
      pattern development and dynamic interactions between eyespots. A substantial part
      of an eyespot can be surgically removed and is then reconstructed by
      regeneration. Strikingly, ectopic patterns are induced by damage at a background
      (eyespotless) area, but focal damage did not change the eyespot size. Early
      stages of damage repair were accompanied by calcium oscillations. These results
      demonstrate that fish eyespots are determined by serial induction, which is
      likely based on a reaction-diffusion mechanism. These findings suggest
      mechanistic similarities between the fish and butterfly systems.

PMID- 22375252
TI  - Child Rights: What can we do in Oman?

PMID- 22375254
TI  - "Between a Rock and a Hard Place": The discordant views among medical teachers
      about anatomy content in the undergraduate medical curriculum.
AB  - The last two decades of medical education have been marked by a persistent push
      towards curricular reform. Anatomy as a discipline, the unshakable foundation of
      medical teaching for hundreds of years, has been at the centre of this
      development. Although it is widely agreed that for doctors to be competent, they
      need an adequate knowledge of anatomy underpinning medicine, there is much less
      agreement over the quantity required, and who should decide and define it. Many
      clinicians feel medical students are being under-trained in this basic medical
      science before reaching the clinical stages. Professional accreditation boards
      advocate the reduction of factual information in undergraduate medical courses.
      Anatomists complain of a progressive erosion of the time allocated to the
      subject. Caught in the midst of this controversy is the student of anatomy who is
      left bewildered and confused about what is required from him to become a safe and
      competent health professional. The way forward might, first, be for medical
      schools to facilitate discussions between students, anatomy professors, and
      clinicians to bring these divergent perspectives into alignment. Second, the
      anatomists need to re-invent themselves in two principal frameworks: first, to
      present the subject in the context within which it will be utilised by the
      student, and second to employ the overwhelming learning tool of today, i.e.
      technology, in their teaching and assessment of the subject.

PMID- 22375253
TI  - The role of oxidative stress and antioxidants in diabetic complications.
AB  - Diabetes is considered to be one of the most common chronic diseases worldwide.
      There is a growing scientific and public interest in connecting oxidative stress
      with a variety of pathological conditions including diabetes mellitus (DM) as
      well as other human diseases. Previous experimental and clinical studies report
      that oxidative stress plays a major role in the pathogenesis and development of
      complications of both types of DM. However, the exact mechanism by which
      oxidative stress could contribute to and accelerate the development of
      complications in diabetic mellitus is only partly known and remains to be
      clarified. On the one hand, hyperglycemia induces free radicals; on the other
      hand, it impairs the endogenous antioxidant defense system in patients with
      diabetes. Endogenous antioxidant defense mechanisms include both enzymatic and
      non-enzymatic pathways. Their functions in human cells are to counterbalance
      toxic reactive oxygen species (ROS). Common antioxidants include the vitamins A,
      C, and E, glutathione (GSH), and the enzymes superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx), and glutathione reductase (GRx). This review
      describes the importance of endogenous antioxidant defense systems, their
      relationship to several pathophysiological processes and their possible
      therapeutic implications in vivo.

PMID- 22375255
TI  - Sociodemographic and Clinical Characteristics of Patients attending Psychotherapy
      in a Tertiary Care Hospital in Oman.
AB  - OBJECTIVES: There is significant evidence that psychotherapy is a pivotal
      treatment for persons diagnosed with Axis I clinical psychiatric conditions;
      however, a psychotherapy service has only recently been established in the Omani
      health care system. This study aimed to investigate the sociodemographic and
      clinical characteristics of attendees at a psychotherapy clinic at a tertiary
      care hospital. METHODS: An analysis was carried out of 133 new referrals to the
      Psychotherapy Service at Sultan Qaboos University Hospital, a tertiary care
      hospital. RESULTS: The majority of referrals were females (59%), aged 18-34
      years, employed (38%), had <=12 years of formal education (51%), and were single
      (54%). A total of 43% were treated for anxiety disorders (including obsessive
      compulsive disorder), while 22% were treated for depression. A total of 65% were
      prescribed psychotropic medications. The utilisation of the Psychotherapy Service
      and its user characteristics are discussed within the context of a culturally
      diverse Omani community which has unique personal belief systems such as in
      supernatural powers (Jinn), contemptuous envy (Hassad), evil eye (Ain) and
      sorcery (Sihr) which are often used to explain the aetiology of mental illness
      and influence personal decisions on utilising medical and psychological
      treatments. CONCLUSION: Despite the low number of referrals to the Psychotherapy
      Service, there is reason to believe that psychotherapy would be an essential tool
      to come to grips with the increasing number of mental disorders in Oman.

PMID- 22375256
TI  - Early versus Late Parenteral Nutrition in Very Low Birthweight Neonates: A
      retrospective study from Oman.
AB  - OBJECTIVES: The aim of this study was to compare the biochemical parameters,
      weight gain, osteopenia and phosphate supplementation in very low birth weight
      (VLBW) neonates receiving early versus late parenteral nutrition (EPN versus
      LPN). METHODS: A RETROSPECTIVE STUDY WAS UNDERTAKEN IN THE LEVEL III NEONATAL
      INTENSIVE CARE UNIT AT SULTAN QABOOS UNIVERSITY HOSPITAL, OMAN: from January 2007
      to October 2008 (LPN group, n = 47) and from January 2009 to June 2010 (EPN
      group, n = 44). Demographic data, anthropometric and laboratory parameters were
      extracted from the electronic record system. RESULTS: The mean age of PN
      initiation was LPN = 47.3 hours versus EPN = 14.3 hours. Biochemical parameters
      analysed during the first week of life revealed a reduction in hypernatraemia
      (12.7% versus 6.8%) and non-oliguric hyperkalemia (12.7% versus 6.8%) in EPN,
      with no significant differences in acidosis and urea levels between the two
      groups. Hyperglycemia >12 mmol/L in <1000g was higher in EPN. Nutritional
      parameters in 81 babies who survived/stayed in the unit up to a corrected
      gestational age (CGA) of 34 weeks (40 in LPN and 41 in EPN), revealed a reduction
      in metabolic bone disease (osteopenia of prematurity [OOP], 17.5% versus 7.3%)
      and the need for phosphate supplementation (22.5% versus 7.3%) in the EPN group.
      There was no increase in acidosis or cholestasis. No difference was noted in
      albumin levels, time to full feeds, time to regain birthweight and mean weight
      gain per day till 34 weeks corrected CGA. CONCLUSION: EPN in VLBW newborns is
      well tolerated and reduces hypernatraemia, non-oliguric hyperkalemia, OOP and the
      need for phosphate supplementation.

PMID- 22375257
TI  - Biomedical publications profile and trends in gulf cooperation council countries.
AB  - OBJECTIVES: There is a dearth of studies examining the relationship between
      research output and other socio-demographic indicators in the Gulf Cooperation
      Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the
      United Arab Emirates). The three interrelated aims of this study were, first, to
      ascertain the number of biomedical publications in the GCC from 1970 to 2010;
      second, to establish the rate of publication according population size during the
      same period and, third, to gauge the relationship between the number of
      publications and specific socio-economic parameters. METHODS: The Medline
      database was searched in October 2010 by affiliation, year and publication type
      from 1970 to 2010. Data obtained were normalised to the number of publications
      per million of the population, gross domestic product, and the number of
      physicians in each country. RESULTS: The number of articles from the GCC region
      published over this 40 year period was 25,561. Saudi Arabia had the highest
      number followed by Kuwait, UAE, and then Oman. Kuwait had the highest profile of
      publication when normalised to population size, followed by Qatar. Oman is the
      lowest in this ranking. Overall, the six countries showed a rising trend in
      publication numbers with Oman having a significant increase from 1990 to 2005.
      There was a significant relationship between the number of physicians and the
      number of publications. CONCLUSION: The research productivity from GGC has
      experienced complex and fluctuating growth in the past 40 years. Future prospects
      for increasing research productivity are discussed with particular reference to
      the situation in Oman.

PMID- 22375258
TI  - Types of Bacteria associated with Neonatal Sepsis in Al-Thawra University
      Hospital, Sana'a, Yemen, and their Antimicrobial Profile.
AB  - OBJECTIVES: This study was undertaken to investigate the organisms causing sepsis
      in the Neonatal Unit at Al-Thawra Hospital, Sana'a, Yemen, determine their
      resistance to antibiotics, and recommend policy for empirical treatment. METHODS:
      A total of 158 neonates having one or more signs of sepsis, and aged from 0 to 28
      days, were enrolled in this study. A blood sample was taken from each subject,
      cultured, and then antibacterial susceptibility tests were performed for
      isolates. RESULTS: 90 (57%) cases yielded positive cultures. Early-onset sepsis
      showed higher positive culture results (61.7%) than late-onset sepsis (32%).
      Significant positive culture results were found among the group with birth weight
      0.9-2 Kg (78.6%). Gram negative bacteria constituted 97.8% of the total isolates,
      of which Klebsiella pneumoniae was the predominant pathogen (36.7%), followed by
      Pseudomonas species (30.0%). The commonest symptoms among the cases were
      respiratory distress (72.2%), jaundice (62.2%), cyanosis (51.1%), and lethargy
      (47.8%); the mortality rate was 27.8%. All Gram negative bacterial isolates were
      sensitive to imipenem and some isolates were sensitive to fourth-generation
      cephalosporins, but most isolates were highly resistant to the majority of other
      antibiotics tested. CONCLUSION: Gram negative organisms were the most frequent
      causative agents of bacterial sepsis, which is a significant cause of mortality
      and morbidity in the newborn, and particularly in those of very low birth weight.
      It can also be concluded that imipenem and fourth-generation cephalosporins can
      be used for empirical treatment of bacterial sepsis.

PMID- 22375259
TI  - Comparative Effects of Glibenclamide and Metformin on C-Reactive Protein and
      Oxidant/Antioxidant Status in Patients with Type II Diabetes Mellitus.
AB  - OBJECTIVES: This study aimed to compare the effects of metformin and
      glibenclamide on high sensitivity serum C-reactive protein (hs-CRP) and oxidative
      stress, represented by serum malondialdehyde (MDA) and total antioxidant status
      (TAS) in newly-diagnosed patients with Type 2 diabetes mellitus (DM) at baseline
      and after 2 months of therapy in comparison to controls. METHODS: The subjects,
      recruited from Al-Wafaa Centre for Diabetes Management and Research, Iraq,
      November 2009 to January 2011, were 103 newly-diagnosed Type 2 DM patients; 53
      were prescribed metformin and 50 glibenclamide. The control group was 40
      apparently healthy volunteers. Blood samples were taken from all subjects after
      overnight fasting. Sera were separated and assays of hs-CRP, MDA and TAS were
      done. After 2 months monotherapy, the blood samples and assays were repeated.
      RESULTS: There were significant differences between patients prescribed metformin
      and glibenclamide and the controls with regard to serum hs-CRP, MDA and TAS.
      There was a significant reduction in the serum MDA and a significant raise in the
      serum TAS levels, with no significant effects on serum hs-CRP levels after
      metformin therapy, but no significant effects on these parameters after
      glibenclamide therapy. The percentage of variation in these parameters after both
      drugs, showed a significant raise in serum TAS levels with the metformin therapy
      with no significant effects in serum MDA and hs-CRP. CONCLUSION: Metformin
      positively affected the oxidant/antioxidant balance in newly-diagnosed Type 2 DM
      patients with no significant effects on acute phase reaction protein.
      Glibenclamide had no significant effects on oxidant/antioxidant balance and acute
      phase reaction protein.

PMID- 22375260
TI  - Magnitude and Causes of Low Vision Disability (Moderate and Severe Visual
      Impairment) among Students of Al-Noor Institute for the Blind in Al-Hassa, Saudi
      Arabia: A case series.
AB  - OBJECTIVES: This study aimed to estimate the magnitude and causes of low vision
      disability (severe visual impairment [SVI] and moderate visual impairment [MVI])
      among students at Al-Noor Institute for the Blind (NIB) in Al-Hassa, Saudi Arabia
      in 2006. METHODS: An optometrist conducted refraction of 122 eyes of the 61
      students (27 boys and 34 girls) with MVI (vision <6/18 to 6/60) and SVI (vision
      <6/60 to 3/60). Ophthalmologists examined the anterior and posterior segments,
      and analysed the outcomes of additional investigations to finalise the diagnosis.
      The results were categorised as 'preventable', 'treatable' and 'not amenable to
      treatment'. The low vision care was also reviewed. RESULTS: In 12 (9.8%) eyes,
      visual acuity was >=6/18 and in 28 (23%) eyes, it was <3/60. MVI and SVI were
      found in 82 eyes (67.2%). Hereditary retinal disorders were found in 68 (55.7%)
      eyes. Although refractive errors were found in 112 (91.8%) eyes, isolated
      refractive error was found in only 9 students. Congenital glaucoma and cataract
      were responsible for visual impairment in 16 (13.1%) and 9 (7.4%) eyes. These
      students were prescribed optical and non-optical low vision aids. CONCLUSION:
      Retinal disease was the main cause of SVI and MVI in our series. Some students at
      Al-Noor Institute for the Blind have curable low vision conditions.
      Rehabilitation of low vision disability should be different from that offered to
      the absolutely blind.

PMID- 22375261
TI  - Trends of Obesity and Overweight among College Students in Oman: A cross
      sectional study.
AB  - OBJECTIVES: Body mass index (BMI), total body fat (TBF), and physical activity in
      relation to obesity and overweight prevalence among Omani students were studied.
      METHODS: A cross-sectional study of 202 Omani students (101 males and 101
      females) from Sultan Qaboos University (SQU) was carried out. Data were collected
      by interview using a structured questionnaire. Weight, TBF and physical activity
      score (PAS) were measured using TANITA scales, and height measured using a
      standardised measuring tape. RESULTS: SUBJECTS WERE CLASSIFIED BASED ON BMI AS:
      underweight (2.48%), normal weight (69.31%), overweight (26.73%) and obese
      (1.49%). According to TBF, 32.67% of students had low body fat scores (BFS),
      26.73% high BFS and 22.28% very high BFS. Low BFS was insignificantly less likely
      with the increase in the mean hours of weekly exercising, (odds ratio [OR] =
      0.708; 95% confidence interval [CI] = 0.448, 1.119) and the PAS (OR = 0.728; 95%
      CI= 0.562, 0.944). Among high and very high BFS students, the mean hours of
      weekly exercising (6.73+/-1.20) and physical activity scores (7.51+/-1.67) were
      higher than those of healthy students. Nutrition knowledge was higher among
      healthy students compared to low BFS, and high and very high BFS subjects. Higher
      nutrition knowledge was associated with a non-significant lower risk of low BFS
      (OR = 0.986; 95% CI = 0.958, 1.015), high and very high BFS (OR = 0.984; 95% CI =
      0.961, 1.008). CONCLUSION: High and very high BFS were prevalent among subjects
      with sedentary lifestyles. Nutritional and physical activity interventions should
      be introduced to combat the problem of overweight students.

PMID- 22375262
TI  - Faculty and students' perceptions of student experiences in a medical school
      undergoing curricular transition in the United arab emirates.
AB  - OBJECTIVES: In 2008, the Gulf Medical College in the United Arab Emirates
      underwent a curricular change from a discipline-based to an organ-system-based
      integrated curriculum. In this context, this study aimed to compare the faculty
      and students' perceptions of the student experiences with the new curriculum.
      METHODS: Data were collected from faculty and second-year students in the
      integrated curriculum using the Dundee Ready Education Environment Measure
      (DREEM). Data collected were transferred to Predictive Analytics Software,
      Version 18. Global and domain scores were assessed with the Wilcoxon Rank-Sum
      Test. Percentage agreement, disagreement and uncertainty were assessed by the z
      test for proportion. RESULTS: There were no significant differences between the
      total DREEM scores of faculty (139/200) and students (135/200). The faculty
      perceived that the students were experiencing significantly more positive
      learning as indicated by the domain score of "Students' Perceptions of Learning".
      Proportions of agreement between faculty and students showed that more faculty
      members than students perceived the need for increased feedback to students and a
      greater emphasis on long term learning. CONCLUSION: The study showed that the
      faculty and students had similar perceptions about the student experiences in the
      integrated curriculum. Areas necessitating remedial measures were the need for
      faculty to learn constructive feedback techniques and an emphasis on long term
      learning in the new curriculum.

PMID- 22375263
TI  - What are Patients' Concerns about Medical Errors in an Emergency Department?
AB  - OBJECTIVES: Concerns about medical errors have recently increased. An
      understanding of how patients conceptualise medical error would help health care
      providers to allay safety concerns and increase patient satisfaction. The aim of
      this study was to evaluate patients' worries about medical errors and their
      relationship with patient characteristics and satisfaction. METHODS: This
      descriptive cross-sectional study was done in the Emergency Department (ED) of a
      university hospital over a one week period in October 2008. A questionnaire was
      used to assess patients' worries about medical errors and their satisfaction
      levels both at an initial interview and by telephone 7 days after discharge. Data
      were gathered and analysed by chi2, t-tests and logistic regression. RESULTS: Of
      638 patients interviewed, 61.6% declared their satisfaction rate as good to
      excellent; (93 [14.6%] as poor; 152 [23.8%] as fair; 296 [46.4%] as good; 97
      [15.2%] as excellent). A total of 48.3% of patients (44.5-52%, with confidence
      interval 95%) were concerned about the occurrence of at least one medical error.
      There was a clear relationship between the general satisfaction rate and having
      at least one concern about a medical error (Chi-square, P <0.001). CONCLUSION:
      This study showed that many patients were concerned about medical errors during
      their emergency care. Due to the stressful situation in EDs, patients' safety and
      satisfaction could be improved by a better understanding of patient concerns,
      education of ED staff and an improvement in the patient-doctor relationship.

PMID- 22375264
TI  - Technicity as a quality indicator of excellence in gynaecology.
AB  - OBJECTIVES: The objective of this study was to calculate the technicity index
      (TI) for hysterectomies at a tertiary care university hospital in Oman. METHODS:
      This is a retrospective chart review of patients who had hysterectomies at Sultan
      Qaboos University Hospital (SQUH), a tertiary care university hospital. Profiles
      were reviewed for all patients who had hysterectomies at SQUH in the period 2003
      2009. The cumulative frequencies for all types of hysterectomies were tallied and
      the year-specific TI was calculated. RESULTS: Overall, we enumerated a total of
      258 hysterectomies, of which 6 (2.3%) were laparoscopic assisted hysterectomies,
      42 (16.3%) vaginal hysterectomies, and 208 (80.6%) total abdominal
      hysterectomies. The average TI was 19% (48/258), and it ranged from 11% to 24%.
      The trend of change fluctuated over the years starting with 16% (2003) and
      increasing gradually during 2004-2006, but then declining again during 2007-2008
      (trend P value 0.02). This low and fluctuating trend was mainly attributed to the
      inconsistency in the availability of trained surgeons and laparoscopic equipment.
      CONCLUSION: TI at our institution can be improved by increasing the number of
      minimally invasive hysterectomies through providing more trained surgeons and
      laparoscopic equipment.

PMID- 22375265
TI  - Child Maltreatment: Types and effects: Series of six cases from a university
      hospital in Oman.
AB  - Child maltreatment (CM) is common worldwide, and can take many forms. It may even
      endanger the child's life, especially when younger children are the victims. CM
      affects the child's quality of life and consequently leads to long term issues to
      be dealt with by the child, family and community. This case series discusses six
      children who have been subjected to CM, and diagnosed by the child protection
      team of the departments of Child Health and Behavioural Medicine at Sultan Qaboos
      University Hospital (SQUH), Oman. The aim of this case series is to increase the
      level of awareness of CM among Oman's medical professionals and to highlight the
      difficulties encountered in diagnosing and providing optimal care for these
      children. Although treatment is provided in Oman's health care system, it is
      clear that there are gaps in the existing system which affect the quality of
      child protection services provided to the children and their families.

PMID- 22375266
TI  - Misdiagnosis of Myasthenia Gravis and Subsequent Clinical Implication: A case
      report and review of literature.
AB  - The autoimmune disease, myasthenia gravis (MG), can mimic a variety of
      neurological disorders leading to a delay in diagnosis and treatment. On
      occasions, misdiagnosis of MG could lead to unnecessary and potentially harmful
      therapeutic interventions. We report on a 12 year-old boy, in whom MG was
      mistaken for meningitic sequelae and subsequently for critical
      neuropathy/myopathy resulting in considerable morbidity for nearly a decade.
      Subsequent correct diagnosis and optimal management resulted in significant
      improvement in his functional status. We discuss the importance of considering MG
      as one of the potential differential diagnoses among cases of recurrent
      respiratory pump failure, or unexplained bulbar symptoms where documentary proof
      of the previous diagnoses including work-up for MG is lacking. We also review the
      literature on MG misdiagnosis and highlight the potential pitfalls in MG
      diagnosis.

PMID- 22375267
TI  - Tracheobronchopathia Osteochondroplastica: Case report and literature review.
AB  - Tracheobronchopathia osteochondroplastica (TPO) is a rare, benign condition
      involving the trachea. TPO is characterised by osteocartilaginous nodules
      developing within the submuscosa of the trachea, sparing the posterior wall. We
      present the first documented case of TPO in Oman in a 25 year-old Omani male who
      presented with a recurrent, productive cough from which he had suffered
      throughout the previous two years. Diagnosis was made by characteristic computed
      tomography scan, bronchoscopic findings, and a histopathological examination.

PMID- 22375268
TI  - Retrograde (fundus first) Laparoscopic Cholecystectomy in Situs Inversus Totalis.
AB  - Situs inversus totalis (SIT) is an uncommon anomaly characterised by
      transposition of organs to the opposite side of the body in a mirror image of
      normal. It may cause difficulties in the diagnostic and therapeutic management of
      abdominal pathology due to the mirror-image anatomy. We report the management of
      a case of symptomatic cholilithiasis with emphasis on its surgical technique.

PMID- 22375269
TI  - Weak Radial Artery Pulse: An unusual congenital cause.
AB  - We present an 11year-old boy with a weak right radial pulse, and describe the
      successful application of vascular ultrasound to identify the ulnar artery
      dominance and a thin right radial artery with below normal Doppler flow velocity
      that could explain the discrepancy. The implications of identifying this anomaly
      are discussed.

PMID- 22375271
TI  - Global Aphasia without Hemiparesis: A neuroradiologic correlation.

PMID- 22375270
TI  - Infective Endocarditis of the Aortic Valve caused by Pseudomonas aeruginosa and
      Treated Medically in a Patient on Haemodialysis.
AB  - Infective endocarditis (IE) in patients on dialysis is a serious infection with a
      high mortality rate. It is usually caused by Gram positive bacteria with Gram
      negative organisms being relatively rare as a cause. Recommended treatment
      usually involves surgical valve replacement and the extended use of antibiotics.
      Successful treatment with antibiotics alone is rare. We report a case of IE
      caused by Pseudomonas aeruginosa in a patient on dialysis treated solely with
      antibiotics.

PMID- 22375272
TI  - Re: Acute Coronary Syndrome, Diabetes and Hypertension: Oman must pay more
      attention to chronic non-communicable diseases.

PMID- 22375273
TI  - Re: Dengue Haemorrhagic Fever presenting as Acute Abdomen.

PMID- 22375274
TI  - Long-term Effects of Multiple Glucocorticoid Exposures in Neonatal Mice.
AB  - Glucocorticoids (GCs) such as dexamethasone (DEX) or betamethasone are repeatedly
      administered for up to a month to prematurely born infants as a treatment for
      chronic lung dysfunction. Results of clinical trials have shown that the use of
      GCs in these infants induces long-term deficits in neuromotor function and
      cognition. We have previously shown that a single exposure to clinically relevant
      doses of DEX or other GCs in the mouse during a period corresponding to the human
      perinatal period produces a dramatic increase in apoptotic cell death of neural
      progenitor cells in the developing cerebellum. To provide a model approximating
      more chronic clinical dosing regimens, we evaluated possible behavioral effects
      resulting from repeated exposures to DEX and subsequent GC-induced neuronal loss
      where neonatal mouse pups were injected with 3.0 mg/kg DEX or saline on postnatal
      days 7, 9, and 11 (DEX3 treatment). Adult, DEX3-treated mice exhibited long-term,
      possibly permanent, neuromotor deficits on a complex activity wheel task, which
      requires higher-order motor co-ordination skills. DEX3 mice exhibited impaired
      performance on this task relative to saline controls in each of two independent
      studies involving separate cohorts of mice. Histopathology studies utilizing
      stereological neuronal counts conducted in behaviorally-tested mice showed that
      the DEX3 treatment resulted in a significant decrease in the number of neurons in
      the internal granule layer (IGL) of the cerebellum, although the number of
      neurons in the Purkinje cell layer were unchanged. The results suggest that
      multiple neonatal DEX exposures can produce chronic deficits in fine motor co
      ordination that are associated with cerebellar IGL neuronal loss. 

PMID- 22375275
TI  - Tobacco Control and Children: An International Perspective.
AB  - Tobacco use currently claims >5 million deaths per year worldwide and this number
      is projected to increase dramatically by 2030. The burden of death and disease is
      shifting to low- and middle-income countries. Tobacco control initiatives face
      numerous challenges including not being a high priority in many countries,
      government dependence upon immediate revenue from tobacco sales and production,
      and opposition of the tobacco industry. Tobacco leads to environmental harms,
      exploitation of workers in tobacco farming, and increased poverty. Children are
      especially vulnerable. Not only do they initiate tobacco use themselves, but also
      they are victimized by exposure to highly toxic secondhand smoke. Awareness of
      tobacco adverse health effects is often superficial even among health
      professionals. The tobacco industry continues to aggressively promote its
      products and recognizes that children are its future. The tools and knowledge
      exist, however, to dramatically reduce the global burden of tobacco. In 2003 the
      World Health Organization adopted the Framework Convention on Tobacco Control.
      Aggressive tobacco control initiatives have been undertaken not only in high
      income countries but also in less-wealthy countries such as Uruguay and Thailand.
      Stakeholders must come together in coordinated efforts and there must be a broad
      and sustained investment in global tobacco control.

PMID- 22375276
TI  - Home is Where the Triggers Are: Increasing Asthma Control by Improving the Home
      Environment.
AB  - Asthma remains the most common chronic condition of childhood. Strong evidence
      has linked exposure to allergens and other triggers commonly found in homes to
      allergen sensitization and asthma incidence and morbidity. A growing body of
      evidence has demonstrated that a home visit strategy that includes an
      environmental component that addresses multiple triggers through multiple
      interventions is effective. Such home visits reduce exposure to triggers,
      decrease symptoms and urgent health-care use, and increase quality of life. To
      make home visits widely available will require health-care payor reimbursement,
      government and health plan funding, training and certification of home visitors,
      and active referrals from health-care providers. However, a strategy based solely
      on education and behavior change is limited, because it cannot adequately reduce
      exposures due to adverse housing conditions. Therefore, approaches that address
      substandard housing are needed. These include remediation of existing housing and
      construction of new asthma-friendly homes. Most studies of remediation have made
      relatively narrow and focused improvements, such as insulation, heating, or
      ventilation. Outcomes have been mixed. Studies of new asthma-friendly homes are
      in their infancy, with promising pilot data. Further investigation is needed to
      establish the effectiveness of improving housing. A final strategy is improving
      housing quality through policy change, such as implementation of healthy housing
      guidelines for new construction, enhancement and increased enforcement of housing
      codes, and assuring smoke-free multi-unit homes. The combination of home visits,
      improved housing construction, and policy change has great potential for reducing
      the global burden of asthma.

PMID- 22375277
TI  - Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children.
AB  - The effect of food introduction timing on the development of food allergy remains
      controversial. We sought to examine whether the presence of childhood eczema
      changes the relationship between timing of food introduction and food allergy.
      The analysis includes 960 children recruited as part of a family-based food
      allergy cohort. Food allergy was determined by objective symptoms developing
      within 2 hours of ingestion, corroborated by skin prick testing/specific IgE.
      Physician diagnosis of eczema and timing of formula and solid food introduction
      were obtained by standardized interview. Cox Regression analysis provided hazard
      ratios for the development of food allergy for the same subgroups. Logistic
      regression models estimated the association of eczema and formula/food
      introduction with the risk of food allergy, individually and jointly. Of the 960
      children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had
      eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95%
      CI: 8.4, 5.9-12.1). Among all children, later (>6 months) formula and rice/wheat
      cereal introduction lowered the risk of food allergy. In joint analysis, children
      without eczema who had later formula (OR, 95% CI: 0.5, 0.3-0.9) and later (>1
      year) solid food (OR, 95% CI: 0.5, 0.3-0.95) introduction had a lower risk of
      food allergy. Among children with eczema, timing of food or formula introduction
      did not modify the risk of developing food allergy. Later food introduction was
      protective for food allergy in children without eczema but did not alter the risk
      of developing food allergy in children with eczema.

PMID- 22375278
TI  - Maternal Pre-Pregnancy Obesity and Recurrent Wheezing in Early Childhood.
AB  - A number of studies have linked obesity with asthma in adults and children. Few
      longitudinal studies have evaluated the effect of maternal pre-pregnancy obesity
      on either asthma or early childhood respiratory morbidity, and these have not
      been in urban, nonwhite populations. We sought to determine whether pre-pregnancy
      obesity was associated with recurrent wheezing in an urban, nonwhite population.
      This study includes 1,191 children from the Boston Birth Cohort (1998-present)
      followed prospectively to a mean age of 3.0 +/- 2.4 years with study visits
      aligned with the pediatric primary care schedule. Multivariate logistic
      regression was used to evaluate the associations of maternal pre-pregnancy
      obesity (body mass index >=30) with recurrent wheezing (>=4 lifetime episodes).
      Secondary outcomes included log-transformed cord-blood immunoglobulin E (Phadia),
      and physician diagnoses of eczema and food allergy. Pre-pregnancy obesity was
      present in 20.7% of mothers. Of the 1,191 children, 60 (5%) developed recurrent
      wheezing. Children of obese mothers had an increased risk of recurrent wheezing
      (adjusted odds ratio, 95% confidence interval: 3.51, 1.68-7.32). These
      associations persisted even after adjustment for fetal growth status. In
      contrast, maternal obesity was not associated with eczema or food allergy, and
      was inversely associated with log cord-blood immunoglobulin E (beta, 95%
      confidence interval: -0.34, -0.66 to -0.02). In this predominantly urban,
      multiracial/ethnic birth cohort, maternal pre-pregnancy obesity was associated
      with an increased risk of recurrent wheezing. This association was not explained
      by fetal growth or increased atopy. Maternal pre-pregnancy obesity is a prevalent
      risk factor for respiratory morbidity in this urban, nonwhite population.

PMID- 22375279
TI  - As Needed Use of Inhaled Corticosteroids for Management of Mild Persistent Asthma
      in Children.

PMID- 22375281
TI  - Abstracts of the Annual Meeting of the American Society for Clinical Pharmacology
      and Therapeutics. March 14-17, 2012. National Harbor, Maryland, USA.

PMID- 22375280
TI  - Practical use and risk of modafinil, a novel waking drug.
AB  - OBJECTIVES: Modafinil is a waking drug prescribed to narcolepsy patients, but its
      usage among healthy individuals is increasing to enhance their alertness or to
      mitigate fatigue. This study was conducted to investigate practical use and toxic
      effects on neuro-immune interaction of modafinil. METHODS: This study reviewed
      the significance of psychoactive drugs, and discussed the benefits and risks of
      the application of modafinil, which seems to be ideal as an anti-psychotic or
      anti-fatigue agent. RESULTS: Modafinil is known to have less or no adverse
      effects than those found in traditional psychostimulants such as amphetamine,
      methylphenidate or cocaine. It can be applied as an anti-psychotic or anti
      fatigue agent. However, the waking mechanism of modafinil is yet to be fully
      revealed. Recent studies reported that modafinil may be subject to abuse and
      addiction. In addition prolonged sleeplessness induces stress responses and
      impairs immune function. CONCLUSIONS: Modafinil can be used by anyone, who wishes
      to work late, stay awake, enhance their cognitive reactions, or brighten their
      moods. Users may already be under a great level of stress, i.e. cancer patients
      or soldiers in a battle field. A psychoneuroimmunological approach is thus needed
      to investigate the multi-functional effects of modafinil.

PMID- 22375282
TI  - [Diagnosis and management of febrile urinary tract infections in infancy and
      early childhood - AAP guidelines 2011].

PMID- 22375283
TI  - Sub-micrometer vaterite containers: synthesis, substance loading, and release.

PMID- 22375284
TI  - Synthesis and immunomodulating activity of new analogues of fingolimod.

PMID- 22375285
TI  - Abstracts of the 32nd Annual Dialysis Conference. February 26-28, 2012. San
      Antonio, Texas, USA.

PMID- 22375286
TI  - Abstracts of the American Association of Geriatric Psychiatry (AAGP) Annual
      Meeting.

PMID- 22375287
TI  - [The case report - not just bizarre collection of curiosities].

PMID- 22375290
TI  - Estimating preferences for local public services using migration data.
AB  - Using Swedish micro data, the paper examines the impact of local public services
      on community choice. The choice of community is modelled as a choice between a
      discrete set of alternatives. It is found that, given taxes, high spending on
      child care attracts migrants. Less conclusive results are obtained with respect
      to the role of spending on education and elderly care. High local taxes deter
      migrants. Relaxing the independence of the irrelevant alternatives assumption, by
      estimating a mixed logit model, has a significant impact on the results.

PMID- 22375288
TI  - Risk of sinonasal-cutaneous fistula after treatment for advanced sinonasal
      cancer.
AB  - BACKGROUND AND OBJECTIVES: To determine the rate and the risk factors for
      sinonasal-cutaneous fistula formation after treatment for sinonasal malignancy.
      METHODS: Between 1991 and 2002, 99 patients with advanced sinonasal malignancy
      received radiation therapy +/- surgery. Primary site was maxillary sinus in 30,
      ethmoid sinus in 19, nasal cavity in 32, nasopharynx in 3, and sphenoid sinus in
      15 patients. Eighty-two percent of patients had T4 disease. Sixty-eight percent
      of patients had undergone surgical resection. Median follow-up was 70.6 months.
      RESULTS: Eight patients developed >= grade 3 sinonasal-cutaneous fistulas at a
      median time of 3.8 months after radiation. The overall rates of developing >=
      grade 3 fistulas in the entire group at 2 and 5 years were 6% and 10%,
      respectively. The fistulas were in the medial canthus in seven patients and in
      the infraorbital region in one patient. Fistulas developed exclusively along the
      transfacial incision scar and in patients whose tumors extended to the
      subcutaneous tissues. In univariate analysis, squamous cell carcinoma histology
      (P 1/4 0.008), <= T4a primary tumor category (P 1/4 0.02), and transfacial
      incision (P 1/4 0.02) were associated with increased risk of fistula formation.
      CONCLUSIONS: Histologic subtype, T category, and quality of the skin and the
      underlying supporting tissues after transfacial incision are risk factors for
      sinonasal-cutaneous fistula formation.

PMID- 22375291
TI  - Different effects of ethnic diversity on social capital: density of foundations
      and leisure associations in Amsterdam neighbourhoods.
AB  - This article examines the effect of ethnic diversity on social capital in
      Amsterdam neighbourhoods by looking at the effects of the ethnic diversity of a
      neighbourhood on the social networks that underpin civil society. A distinction
      is made between homogeneous, more individually oriented social networks, on the
      one hand, and horizontal heterogeneous networks on the other. The density of
      foundations-i.e. the number of foundations in a neighbourhood-is used as the
      indicator for the first type of networks and the density of leisure associations
      for the latter type. In addition, the study looks at the effect of a changing
      context in Amsterdam in which ethnic diversity has increasingly come to be
      perceived as problematic by inhabitants and local politicians. The results indeed
      show that ethnic diversity has a different effect on both forms of civil society:
      the horizontal heterogeneous networks suffer more from ethnic diversity than the
      homogeneous networks.

PMID- 22375293
TI  - No place, new places: death and its rituals in urban Asia.
AB  - In many land-scarce Asian cities, planning agencies have sought to reduce space
      for the dead to release land for the living, encouraging conversion from burial
      to cremation over several decades. This has caused secular principles privileging
      efficient land use to conflict with symbolic values invested in burial spaces.
      Over time, not only has cremation become more accepted, even columbaria have
      become overcrowded, and new forms of burials (sea and woodland burials) have
      emerged. As burial methods change, so too do commemorative rituals, including new
      on-line and mobile phone rituals. This paper traces the ways in which physical
      spaces for the dead in several east Asian cities have diminished and changed over
      time, the growth of virtual space for them, the accompanying discourses that
      influence these dynamics and the new rituals that emerge concomitantly with the
      contraction of land space.

PMID- 22375294
TI  - Environmentally influenced urbanisation: footprints bound for town?
AB  - Over the past 30 years, urbanisation has been a prominent phenomenon and various
      drivers have been proposed to explain it. Very few have suggested that the
      degradation of the rural environment was one of them. This paper explores the
      human-environment interface by focusing on the portrayal of these concepts within
      scholarly literature. A systematic literature review was conducted and 147
      articles were examined to determine the direction of the link between the
      environment and human mobility, and if urbanisation was featured. The results
      demonstrate that equal attention is paid to both directions of the environment
      mobility link. Of the articles reviewed, 40 per cent focus on urbanisation, but
      93 per cent of those portray urbanisation as a forcing on the environment, rather
      than an impact of environmental degradation. The lack of support for
      environmentally influenced urbanisation can be explained by coupled system
      complexity, disciplinary research and the silence of those most likely to endure
      environmental change. Understanding these relationships is paramount to the
      promotion of adaptation without eroding resilience or further degrading
      environments.

PMID- 22375295
TI  - Ethnography as relation: the significance of the French Caribbean in the
      ethnographic writing of Michel Leiris.
AB  - This article considers two kinds of connection between Leiris and the French
      Caribbean that between his ideas on ethnography and Martinican Edouard Glissant's
      concept of Relation; and the impact that his encounter with the French Caribbean
      had on those ideas. In 1950 Leiris develops a conception of ethnography as a
      partnership between Western and non-Western societies in which the ethnographer
      is not only politically involved in the societies she or he studies, but also
      trains native ethnographers so that the discipline can become a dialogue - or
      Relation - between the perspectives of 'self' and 'other' on the self's and the
      other's cultures. In two important articles on Leiris, Glissant comments
      approvingly on Leiris's formulation of the difference between his earlier
      phantasy of identification with the colonized and his new politicized stance. In
      fact, however, the difference is less clear-cut: Leiris's writing continues to
      express a complex imbrication of the personal and the political; the political
      commitment can be seen as a 'sublimated' version of the original emotional
      investment. Leiris moves from a desire to achieve 'contact vrai' with the black
      other to a sublimated desire to study societies that are themselves made up of
      contacts with other cultures; and the Caribbean provides the ideal example. But
      the importance of the Caribbean for Leiris lies also in the greater possibilities
      it offers, compared with Africa, for making his own personal 'contacts', through
      his friendship with Cesaire, with politically active Antillean intellectuals, and
      hence laying the foundations for interactive ethnographic partnerships.

PMID- 22375296
TI  - Hypochondria as withdrawal and comedy as cure in Dr. Willibald's Der
      Hypochondrist (1824).
AB  - Balthasar von Ammann's comedy Der Hypochondrist, published in 1824 under the
      pseudonym Dr. Willibald, foregrounds the social, sexual, and political
      implications of hypochondria. The play engages with early nineteenth-century
      medical and popular conceptions of hypochondria to co-opt potentially subversive
      elements and to promote a specific social, sexual, and political agenda. The text
      promotes literature - specifically comedic drama - as a cure for hypochondria.
      Hypochondria functions as a code for withdrawal. The hypochondriac withdraws
      medically from healthy society, gaining exceptional status. He withdraws sexually
      from society by remaining a bachelor, possibly engaged in non-normative sexual
      behaviour. Furthermore, the politically disenfranchised protagonist voices his
      political frustrations via a coded medical metaphor. The hypochondriac poses a
      threefold challenge to the social, sexual, and political order, and the play
      engages with contemporary conceptions of the disease to provide the solution:
      comedy. The text, presented as a cure for hypochondria, replaces the coded
      questioning of the social order via hypochondria with the less threatening code
      of heraldry. A comedy-within-the-comedy uses the hypochondriac's love of heraldry
      to cure him, resulting in the elimination of his medical problems and exceptional
      status, in the purification of his bachelorhood from non-normative elements, and
      in the pre-emption of political frustrations.

PMID- 22375297
TI  - The acceleration of the masculine in early-twentieth-century Berlin.
AB  - In early-twentieth-century Berlin, agents of speed and industrialisation, such as
      the railway, contributed to the seemingly unbridled velocity of urban life.
      Doctors and cultural critics took an ambivalent stance toward the impact of speed
      and technology on the human body. Critics argued that these factors, in
      conjunction with sexual excess and prostitution, accelerated the sexual
      maturation of young men, thereby endangering 'healthy' male sexuality. This
      comparison of Hans Ostwald's socio-literary study Dunkle Winkel in Berlin (1904)
      with Georg Buschan's sexual education primer Vom Jungling zum Mann (1911) queries
      the extent to which speed shaped the understanding of 'the masculine' in pre
      World-War-I Germany. The essay thus examines Ostwald's and Buschan's arguments
      and postulates that speed in the city (Berlin) can be seen as a feminised,
      sexualised force that determined sex in the city. According to this reading, the
      homosexual urban dandy resisted the accelerated modernist urban tempo, whereas
      the heterosexual man and hegemonic, heteronormative masculinity yielded to speed.
      '"Das Verhaltnis"' became a fleeting, momentary alternative to stable marital
      relationships, which in turn contributed to the general 'crisis' of - and in-
      masculinity in early-twentieth-century Berlin.

PMID- 22375298
TI  - American cinema and the construction of masculinity in film in the Federal
      Republic after 1945.
AB  - Since 1945, film in the Federal Republic has maintained an ambivalent
      relationship to American cinema and its embedded ideologies and nowhere is this
      more evident than in (West) German film's representations of masculinity. This
      article focuses on three historical moments when political and social shifts
      resulted in a problematising of male identities in the Federal Republic: the mid
      1950s, the early 1970s and the late 1990s. Cinema responded to a perceived
      destabilisation of gender norms by exploring constructions of German masculinity
      in relation to the ambivalently received models of male identity offered by
      American cinema. With a detailed analysis of three specific examples - Georg
      Tressler's Die Halbstarken (1956), Rainer Werner Fassbinder's Der amerikanische
      Soldat (1970) and Fatih Akin's Kurz und schmerzlos (1998) - this article
      investigates the manner in which German cinema engages with these competing
      conceptions of masculinity and demonstrates the ways in which divergent
      understandings of gender identity can impact on representations of national and
      ethnic identity.

PMID- 22375299
TI  - "Der Bleistift roch nach Rosmarin": the art of foraging in Stifter, Handke, and
      Beuys.
AB  - Taking as its starting point the notion of 'reading' as 'gathering', implied by
      the word Lesen, this essay examines some correspondences between foraging,
      naming, writing, drawing, and reading to establish a clear distinction between
      foraging and collecting more generally. By way of example, three kinds of
      foraging are addressed: berry picking, in Adalbert Stifter's short story Der
      Waldsteig; mushroom collecting, in Peter Handke's fairy-tale Lucie im Wald mit
      den Dingsda; gathering medicinal herbs, in particular rosemary, in the drawings,
      performances, and social sculptures of Joseph Beuys (including Manresa, Barraque
      D'dull Odde, Geruchsplastik, Blitzschlag mit Lichtschein auf Hirsch). In the
      literary and visual works discussed here, foraging and its products are
      therapeutic both physically and spiritually, what Handke terms 'traumerweiternd'.
      Moreover, in the case of Beuys in particular this healing process has explicitly
      social and political implications. The essay also examines foraging as an analogy
      for the construction of meaning and concludes with a discussion of the clearing
      as a privileged space in which foraging and gathering, both literally and
      figuratively, can take place.

PMID- 22375300
TI  - Social welfare as small-scale help: evolutionary psychology and the deservingness
      heuristic.
AB  - Public opinion concerning social welfare is largely driven by perceptions of
      recipient deservingness. Extant research has argued that this heuristic is
      learned from a variety of cultural, institutional, and ideological sources. The
      present article provides evidence supporting a different view: that the
      deservingness heuristic is rooted in psychological categories that evolved over
      the course of human evolution to regulate small-scale exchanges of help. To test
      predictions made on the basis of this view, a method designed to measure social
      categorization is embedded in nationally representative surveys conducted in
      different countries. Across the national- and individual-level differences that
      extant research has used to explain the heuristic, people categorize welfare
      recipients on the basis of whether they are lazy or unlucky. This mode of
      categorization furthermore induces people to think about large-scale welfare
      politics as its presumed ancestral equivalent: small-scale help giving. The
      general implications for research on heuristics are discussed.

PMID- 22375301
TI  - [Community health and social action in the epidemiologic control of infantile
      trachoma, Spain (1932-1939)].
AB  - Within the context of the endemic trachoma that affected different regions of
      Spain until the 1960s, this paper analyses the epidemiological determinants of
      child trachoma and its treatment, based on a preventive care model which
      incorporated the concept of community health that took shape during the interwar
      period. Early detection of cases, together with preventive measures, education,
      therapy and inspections, such as those carried out by visiting nurses, all helped
      to control the disease. Our results reaffirm the validity of the horizontal
      intervention strategies used for improving the sanitary conditions and
      environmental factors responsible for this prevalence of trachoma.

PMID- 22375302
TI  - [Political change, disease and healthcare reform: the response to the Toxic Oil
      Syndrome (Spain, 1981-1998)].
AB  - In 1981, Spain was threatened by the sudden appearance of an epidemic-like
      disease, one which was unknown to that date. The Toxic Oil Syndrome, as it was
      later named after the oil that caused it, thus demanded a response that became
      conditioned by the fact that the biological nature of the disease was unknown,
      but also, significantly by the complex situation in the country at that time.
      Spain was immersed in process of great political change, as well as a difficult
      economic situation, the authorities were obliged to react in not ideal conditions
      and in accordance with the very values that the new model of social relations
      that was being developed. This paper aims to look at the way in which the Toxic
      Oil Syndrome acted as a catalyst and accelerated the healthcare reform that,
      already prior to the outbreak of the epidemic, had been deemed necessary. This
      work focuses mainly on the response of the health system regarding those affected
      by the epidemic, as it was forced to treat a group of people with severe physical
      side effects which would lead to disability within a new framework of social
      relations. It thus aims to illustrate how many of the measures adopted were in
      accordance with the main ideas behind the reform, and also how these measures
      were precursors of those which were later applied to the population as a whole.

PMID- 22375303
TI  - [The journal of A.V. Humboldt in Spain].
AB  - The Spanish diary can surprisingly not be found in his bounded diaries from his
      American travels, but in a separate folder of his legacy in Berlin, where
      Humboldt collected material which he wanted to use for his publication about
      Spain. So it remained undiscovered until recently. Humboldt's notes contain
      geognostic descriptions as well as his observations about climate, vegetation,
      electricity of the atmosphere, etc. The comparison with Humboldt's publication of
      1825 facilitates to gain insight into his scientific methods.

PMID- 22375304
TI  - Be a "great physician" for your patients with type 2 diabetes mellitus.

PMID- 22375305
TI  - Case report: atypical lipomatous tumor with unusual extensive metaplastic
      ossification.
AB  - The presence of metaplastic ossification within atypical lipomatous tumor/well
      differentiated liposarcoma (ALT/WDLPS) is a rare occurrence. When present, bone
      formation is most often found in association with a dedifferentiated component
      arising within the primary tumor. It is important for the radiologist not only to
      recognize the differential diagnosis of a calcified or ossified soft tissue mass
      but also be aware of the various soft tissue neoplasms, both aggressive and non
      aggressive, that may show such features. We report a case of ALT/WDLPS with
      unusual extensive metaplastic bone formation without an element of
      dedifferentiated liposarcoma.

PMID- 22375306
TI  - CT-based quantitative SPECT for the radionuclide 201Tl: experimental validation
      and a standardized uptake value for brain tumour patients.
AB  - We have previously reported on a method for reconstructing quantitative data from
      99mTc single photon emission computed tomography (SPECT) images based on
      corrections derived from X-ray computed tomography, producing accurate results in
      both experimental and clinical studies. This has been extended for use with the
      radionuclide 201Tl. Accuracy was evaluated with experimental phantom studies,
      including corrections for partial volume effects where necessary. The
      quantitative technique was used to derive standardized uptake values (SUVs) for
      201Tl evaluation of brain tumours. A preliminary study was performed on 26
      patients using 201Tl SPECT scans to assess residual tumor after surgery and then
      to monitor response to treatment, with a follow-up time of 18 months. Measures of
      SUVmax were made following quantitative processing of the data and using a
      threshold grown volume of interest around the tumour. Phantom studies resulted in
      the calculation of concentration values consistently within 4% of true values. No
      continuous relation was found between SUVmax (post-resection) and patient
      survival. Choosing an SUVmax cut-off of 1.5 demonstrated a difference in survival
      between the 2 groups of patients after surgery. Patients with an SUVmax<1.5 had a
      70% survival rate over the first 10 months, compared with a 47% survival rate for
      those with SUVmax>1.5. This difference did not achieve significance, most likely
      due to the small study numbers. By 18 months follow-up this difference had
      reduced, with corresponding survival rates of 40% and 27%, respectively. Although
      this study involves only a small cohort, it has succeeded in demonstrating the
      possibility of an SUV measure for SPECT to help monitor response to treatment of
      brain tumours and predict survival.

PMID- 22375308
TI  - Big computers for little engineers.

PMID- 22375307
TI  - A neglect of mental illness.

PMID- 22375309
TI  - Remains of the day.

PMID- 22375310
TI  - Forget cramming.

PMID- 22375311
TI  - Body-snatching flies.

PMID- 22375313
TI  - A new wrinkle in time.

PMID- 22375312
TI  - Backseat drivers.

PMID- 22375314
TI  - Probing the depths.

PMID- 22375315
TI  - Are university labs criminally dangerous?

PMID- 22375316
TI  - It's all in the tail.

PMID- 22375317
TI  - Time to kill off captchas.

PMID- 22375318
TI  - Nature that nurtures.

PMID- 22375320
TI  - The far, far future of stars.

PMID- 22375319
TI  - What makes each brain unique.

PMID- 22375321
TI  - Dinosaurs of the lost continent.

PMID- 22375322
TI  - Gather the wind.

PMID- 22375323
TI  - Blocking HIV's attack.

PMID- 22375324
TI  - The shadow web.

PMID- 22375326
TI  - Hit them with the hockey stick. Interview by David Biello.

PMID- 22375325
TI  - Lifting the black cloud.

PMID- 22375327
TI  - Opting out of overoptimism.

PMID- 22375328
TI  - The dwindling web.

PMID- 22375329
TI  - Regulator needs strong leader and open culture.

PMID- 22375330
TI  - Resignation at troubled regulator could lead to an extensive review.

PMID- 22375331
TI  - Training fails to prepare students for modern workplace, survey says.

PMID- 22375332
TI  - Union members to be balloted on government's pension plans.

PMID- 22375333
TI  - Scepticism over plans to reward hospitals that use NHS safety tool.

PMID- 22375334
TI  - Community staff left reeling from push to create social enterprises.

PMID- 22375335
TI  - Ongoing development suffers as NHS invests training budgets elsewhere.

PMID- 22375336
TI  - Better than any drug.
AB  - If more people exercised regularly it would help reduce incidences of heart
      disease, stroke and diabetes. Nurses should exercise more themselves and be aware
      of its benefits for disease prevention and treatment.

PMID- 22375337
TI  - More than a checklist.
AB  - Prime minister David Cameron is advocating a system that requires hospital nurses
      to check on patients at set intervals. Evidence suggests that 'intentional
      rounding' reduces the use of call bells and improves care. Nurses detect problems
      earlier and enjoy improved interaction with patients.

PMID- 22375338
TI  - Tracking the patient.
AB  - An innovative IT system is alerting community nurses to unplanned admissions and
      improving liaison with ward nurses. The system saves nurses' time and eases the
      admission and discharge process.

PMID- 22375339
TI  - Purchasing power.
AB  - Nurses and GPs are working together in Shropshire to introduce clinically-led
      commissioning, and ensure that the new arrangements improve services despite a
      tough financial climate. Nursing involvement in the new clinical commissioning
      group is active and not 'tokenistic'.

PMID- 22375340
TI  - Auditing urinary catheter care.
AB  - Urinary catheters are the main cause of hospital-acquired urinary tract
      infections among inpatients. Healthcare staff can reduce the risk of patients
      developing an infection by ensuring they give evidence-based care and by removing
      the catheter as soon as it is no longer necessary. An audit conducted in a
      Hampshire hospital demonstrated there was poor documented evidence that best
      practice was being carried out. Therefore a urinary catheter assessment and
      monitoring tool was designed to promote best practice and produce clear evidence
      that care had been provided.

PMID- 22375341
TI  - Optimising nutrition for older people with dementia.
AB  - This article explores interventions that can be undertaken to establish and
      maintain adequate nutritional intake in older people with dementia. This is often
      a problem, particularly in the later stages of the disease. A literature review
      was conducted, which identified 12 articles for inclusion. Most of these articles
      described interventions to maintain adequate nutritional intake in older adults
      with dementia. Although no standardised intervention was reported, some
      approaches did appear to be more successful than others. Further research is
      required on how nurses and nursing assistants can help older people with dementia
      to maintain adequate nutrition. Staff need more time and training to improve
      nutritional intake in this group of patients. In addition, enhanced vigilance
      with respect to eating difficulties and food consumption is necessary.

PMID- 22375342
TI  - Strategies to improve iron status in women at risk of developing anaemia.
AB  - Iron deficiency is one of the most prevalent nutritional deficiency disorders
      worldwide, with teenage girls and women of childbearing age, especially pregnant
      and postpartum mothers, being most affected. Although supplements may be required
      in some instances, simple dietary and lifestyle changes may also help individuals
      to establish a healthy iron status. This article presents useful information that
      nurses and midwives can provide to women during particular life phases such as
      pregnancy, adolescence and old age to improve their iron status.

PMID- 22375343
TI  - Preventing falls in older people.

PMID- 22375344
TI  - Let's do it in 60 minutes.

PMID- 22375345
TI  - Opportunities abroad.

PMID- 22375346
TI  - Under the microscope.

PMID- 22375347
TI  - Bereavement and the DSM5.
AB  - Close personal relationships are very important in our lives. Our closest
      relationships help us regulate our bodies and minds and contribute importantly to
      our sense of wellbeing (Hofer, 1984; Mikulincer, Orbach, & Iavnieli, 1998; Sbarra
      & Hazan, 2008). Losing a close attachment is usually one of the most difficult
      experiences we ever have. Bereavement often leaves us dazed and confused about
      how to understand the loss and navigate the future. Acute grief takes us out of
      our ongoing life and focuses our attention on our deceased loved one. Grief is
      finely tuned to each loss situation with a pattern and course that is unique to
      each person and each relationship.

PMID- 22375348
TI  - Attachment, social support, and responses following the death of a companion
      animal.
AB  - This research tested hypotheses concerning attachment, social support, and grief
      responses to the loss of animal companionship. Participants whose companion cat
      or dog had recently died (N = 429) completed the Attachment Style Questionnaire,
      the Inventory of Complicated Grief, and the Multidimensional Health Profile
      Psychosocial Functioning questionnaires. Both attachment anxiety and attachment
      avoidance were found to be positively associated with respondents' grief,
      depression, anxiety, and somatic symptoms. Social support was found to be
      negatively associated with these outcomes as well as with attachment anxiety and
      attachment avoidance. In multiple regression analyses, attachment anxiety
      incrementally predicted grief, anxiety and somatic symptoms, attachment avoidance
      incrementally predicted grief and depression, and social support incrementally
      predicted all outcomes. Interaction effects of attachment and social support in
      relation to outcomes were not found. The present study's implications and
      limitations are discussed, as are directions for future research.

PMID- 22375349
TI  - The importance of end-of-life care in nursing home settings is not diminished by
      a disaster.
AB  - The emphasis in disaster situations is on preserving life, and this goal is both
      appropriate and laudable. There is a risk, however, that the needs of people who
      are dying can become lost when there is a sudden surge of people needing acute
      intervention. There are significant ethical considerations inherent in society's
      prioritization of care needs across the acute, rehabilitative, and palliative
      spectrum in general, let alone in a disaster situation. These ethical conundrums
      are not the focus of this article. Rather, we anchor our discussion on the
      assumption that care needs are equally valid, and our purpose is to explore the
      issues that impact the provision of quality end-of-life care in nursing home
      settings for those who require this care when a disaster occurs. Nursing home
      residents, in particular, are at heightened risk for experiencing negative
      disaster-related outcomes due to compromised physical or mental health that
      requires skilled nursing care. Moreover, within the already vulnerable nursing
      home population are many people who are receiving palliative end-of-life services
      when a disaster strikes. Education and training in end-of-life services for
      nursing home staff, disaster emergency responders, and other lay people is vital
      to build capacity for adapting the delivery of these services in disaster
      situations in the interest of equity and human rights. Given the present lack of
      guidance in the literature as to what end-of-life care looks like when adapted to
      the context of disaster response, there is also a pressing need for research to
      inform this discussion. The purpose of this article is to draw attention to this
      topic and highlight some of the critical issues, gaps, and opportunities.

PMID- 22375350
TI  - The emergence of thanatology and current practice in death education.
AB  - Thanatology is a recent field that contemplates death studies and employs an
      interdisciplinary approach to practice. This science emerged in a historical
      context marked by intense social, economic, and political changes that
      contributed to the concept of death being excluded from social life. This
      literature review aims to outline the history and evolution ofthanatology in
      Western society, delineating the contextual circumstances that led to its origin
      and drawing special attention to current works on death education. In our post
      modern society, the call for studies in the field of thanatology appears to be
      increasing. However, although there have been significant contributions and
      promising research is underway, there are still many questions to be answered.

PMID- 22375351
TI  - The death distress construct and scale.
AB  - The purpose of this research was to construct a short scale to assess the death
      distress construct, that is, death anxiety, death depression, and death obsession
      as derivatives from the already existing scales. A sample of 630 volunteer
      undergraduates responded to scales of death anxiety, death depression, and death
      obsession. A Pearson correlation matrix was computed using the 51 individual
      items of the three scales. A forced three-factor principal components analysis
      with orthogonal varimax rotation was carried out. Eight items with factor loading
      > 0.5 on each scale was determined. The eight items with highest factor loadings
      on Factor I were with "Death obsession," whereas the Factors II and III were
      labeled: "Death anxiety," and "Death depression." Their alpha reliabilities
      ranged from 0.83 to 0.93, indicating high internal consistency. One week test
      retest reliability ranged between 0.76 and 0.91, indicating temporal stability. A
      single high-loaded factor of death distress was disclosed, demonstrating the
      discriminant validity of the death distress construct and scale. Women obtained a
      significantly higher mean scores on all three factors. It was concluded that the
      aforementioned three factors were sufficiently independent to justify their use
      in assessing partially distinct sub-constructs as sub-components of the generic
      high-order factor of death distress, with empirical and clinical implications.

PMID- 22375352
TI  - When a nurse is attacked!

PMID- 22375353
TI  - Nurses and public policy.

PMID- 22375354
TI  - What's "Right to Work" really about?

PMID- 22375355
TI  - [Ischemia reperfusion: an unavoidable phase of transplant procedures].
AB  - Transplanted organs are inevitably exposed to ischemia-reperfusion injury. Cold
      preservation is also used to reduced metabolic processes during ex vivo transport
      but triggers a complex pathophysiological syndrome which is responsible for
      delayed graft function after reperfusion. Ischemia-reperfusion injury is also
      associated with chronic graft dysfunction.

PMID- 22375356
TI  - [Sterile inflammatory response to ischemia-reperfusion injury: immediate and long
      term consequences on graft function].
AB  - Solid organs used for transplantation are subjected to ischemia-reperfusion,
      which induces cellular stress and tissue necrosis. Ischemia-reperfusion injury
      activates the complement cascade and triggers the release of danger-associated
      molecular signals. The latter bind to pattern-recognition receptors on innate
      immune cells, thereby eliciting a sterile inflammatory response that, together
      with complement activation, increases tissue damage. This sterile inflammatory
      response also triggers maturation of antigen-presenting cells (macrophages and
      dendritic cells), enabling them to present donor antigens efficiently to
      recipient lymphocytes. By initiating adaptive alloimmune responses in the
      recipient, innate immunity plays a central role in the rejection process, which
      remains a major cause of late graft failure. Strategies capable of dampening the
      sterile inflammatory response induced by ischemia-reperfusion could therefore be
      beneficial, both for immediate post-transplantation graft function and for long
      term outcome.

PMID- 22375357
TI  - [Improving donor heart preservation ex vivo].
AB  - There is a shortage of heart donors. Some available organs are lost through
      deterioration prior to transplantation. Indeed, from the moment of brain death
      until reperfusion in the recipient, cardiac grafts (and also kidney, lung and
      liver grafts) can undergo irreversible damage due to cardioplegia, the harvesting
      procedure, and hypothermic transport. The noxious phenomena occurring during cold
      ischaemia and myocardial reperfusion have been studied for more than 40 years. It
      was long believed that only the ischaemic phase was harmful, through depletion of
      energy stores, ionic imbalance, and metabolic disruption. We now know that the
      heart graft can also be damaged during the reperfusion phase, through calcium
      overload, free radical production, and mitochondrial changes. Preconditioning and
      post-conditioning procedures are being developed to protect the ischemic organ.

PMID- 22375358
TI  - [Changes in organ donor epidemiology and new strategies for kidney preservation].
AB  - Changes in the epidemiology of brain death are leading the transplant community
      to use more marginal grafts from so-called extended criteria donors. Current
      preservation techniques, while simple, are no longer adequate for these organs,
      which harbor chronic lesions making them very sensitive to ischemia-reperfusion
      injury. New preservation solutions are needed, along with machine perfusion
      techniques (dynamic preservation) and normothermic preservation phases.

PMID- 22375359
TI  - [Use of new non-nephrotoxic immunosuppressive drugs in kidney transplantation,
      especially after ischemia-reperfusion injury].
AB  - Medium- and long-term renal graft survival depends on 4 main factors: the quality
      of the harvested graft, ischemia-reperfusion injury during harvesting and re
      implantation, rejection, and the nephrotoxicity of certain drugs (especially
      immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive
      drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class
      discovered in the late 1970s and currently representing a basic component of all
      immunosuppressive protocols for solid organ graft recipients. The renal tubular
      and vascular toxicity of anticalcineurins is due to their immunosuppressive
      mechanism: they block the calcineurin pathway and thereby prevent transmission of
      the first signal from the T cell receptor to the nucleus, which normally triggers
      cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed,
      especially for grafts of poor quality or subject to severe ischemia-reperfusion
      injury. Attention is turning to "old " molecules such as anti-thymocyte
      globulins, but exciting new immunosuppressants are now appearing. Alefacept is a
      fusion protein that binds to the immunological synapse-associated molecule CD2,
      which normally interacts with LFA-3. Belatacept, another fusion protein, blocks
      the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being
      developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a
      Jak inhibitor.

PMID- 22375360
TI  - [New approaches in dystonia (clinical features, genetic issues and
      pathophysiology].
AB  - Dystonia is defined by the occurrence of abnormal twisting movements and posture,
      and may be generalized or focal. Many subtypes of dystonias have been described,
      including monogenic forms (eg. DYT1 and DYT6), secondary dystonias related to
      metabolic disorders, forms due to brain lesions (including post-anoxic brain
      injury), and tardive dystonia. Dystonia may also be associated with myoclonus
      (myoclonus-dystonia, DYT11) or parkinsonism (rapid-onset dystonia parkinsonism
      DYT1). Paroxystic dystonias are a subgroup of paroxysmal dyskinesias. Diagnosis
      is based mainly on clinical features, age at onset, outcome, associated
      neurological signs, and brain MRI. Until recently, basal ganglia dysfunction and
      alterations of the sensory-motor network with maladaptive cortical plasticity
      were the core pathophysiological features of dystonia. Cerebellar and cerebello
      thalamic anatomic-functional abnormalities may also play a role. The main
      objectives of this review are to highlight the principal characteristics of
      dystonias and to provide an overview of known culprit genes and environmental
      factors. Current pathophysiological knowledge, including anatomic-functional
      abnormalities, is summarized.

PMID- 22375361
TI  - [Medical aspects of the medical treatment in dystonia].
AB  - Dystonias encompass a wide range of movement disorders characterized mainly by
      abnormal postures or movements. Because of this semiological and etiological
      heterogeneity, robust clinical trials are rare. Specific etiological treatments
      are available for only a few forms (e.g. Wilson's disease and dopa-responsive
      dystonia), which places the emphasis on symptomatic treatment. This is based on
      the combinations of three complementary approaches: drug therapy
      (anticholinergics, tetrabenazine and benzodiazepines are first-line drugs, but
      many others have been tested in small clinical trials), botulinium toxin
      injections in case of focal dystonia or focal targets in patients with more
      widespread dystonia, and physiotherapy. This review provides a short overview of
      available treatments and proposes a basic therapeutic strategy for dystonic
      patients.

PMID- 22375362
TI  - [Epidemiology, etiology and mechanism of atrial fibrillation].
AB  - Atrial fibrillation affects about 750 000 people in France, and its incidence is
      growing rapidly as the population ages. The main cause used to be rheumatic heart
      disease, but arterial hypertension is now responsible for about 80 % of cases.
      The mechanisms are complex. Many cases are due to pulmonary vein foci, but
      comorbidities can lead to different mechanisms.

PMID- 22375363
TI  - [Thrombotic risk factors and antithrombotic treatment in atrial fibrillation].
AB  - Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, and its
      incidence is rising as the population ages. AF is therefore a growing source of
      cardiovascular morbidity and mortality due to thromboembolic complications and
      heart failure. The risk of embolic stroke is multiplied by about 5.6-fold in non
      rheumatic AF and by 17.6-fold in rheumatic AF Strokes due to AF are often fatal
      or disabling. Paroxysmal and permanent fibrillation are associated with a similar
      thromboembolic risk. Embolic complications arise from the left atrium or the left
      atrial appendage. Known risk factors in patients with AF include a history of
      thromboembolism or stroke, age > 75 years, heart failure, rheumatic valve
      disease, mechanical prosthetic valves, arterial hypertension and diabetes
      mellitus. Ischemic cardiomyopathy, female gender and atherosclerotic vascular
      disease are associated with an intermediate risk of thromboembolism. Vitamin K
      antagonist therapy targeting an INR of 2 to 3 reduces the risk of stroke by two
      thirds in patients with AF, and causes bleeding in 1.4 % to 3.6 % of patients.
      The bleeding risk can be evaluated with the CHADS2 scale. Aspirin (75/300 mg per
      day) reduces the risk of cerebral thromboembolism by about 21%. Current
      guidelines recommend vitamin K antagonist or dabigatran anticoagulation for
      patients with a CHADS2 score of 2. Patients with a score of 0 should receive
      either aspirin or no drug therapy, while patients with a score of 1 may receive
      either a vitamin K antagonist or aspirin. After successful AF ablation, the
      existing antithrombotic strategy should be pursued New strategies based on
      antithrombin or anti-Xa medications will probably have a better risk-benefit
      ratio.

PMID- 22375364
TI  - [Antiarrhythmic therapy in atrial fibrillation].
AB  - The choice of antiarrhythmic therapy for atrial fibrillation is directly
      dependent on the clinical presentation. This article describes the treatment of
      acute attacks associated with paroxysmal forms, and also of more persistent
      forms. First-line relapse prevention is based on antiarrhythmic drugs, but other
      options such as atrial catheter ablation have recently been developed. Ablation
      of the normal conducting atrioventricular pathway and direct atrial surgery are
      also discussed.

PMID- 22375365
TI  - [Atrial fibrillation in an acute stroke unit].
AB  - Contrasting with the abundant literature dedicated to atrial fibrillation (AF)
      and to the use of new oral anticoagulants in this setting, very few recent
      studies have focused on patients with AF-associated stroke. From November 2010 to
      March 2011, we conducted a small prospective 4-month study in the stroke units of
      Lariboisiere and Bicetre hospitals. Fifty patients with FA and stroke were
      included (14% of all strokes), including 45 patients with cerebral infarcts (CI),
      3 with transient ischemic attacks (TIA) and 2 with intracerebral hemorrhage
      (ICH). The results of this study, together with a review of the sparse relevant
      literature, underline the following points: these patients tend to be older and
      more frequently female than in recent clinical trials; TIAs are rare; these
      patients have numerous vascular risk factors and associated cerebrovascular
      diseases such as atheroma and leukoaraiosis; CI is often extensive and
      hemorrhagic; AF is discovered in a stroke unit in 40% of cases and is paroxystic
      in 33% of cases, with no consensus on the potential regulation; there is massive
      underuse of VKA in patients with known AF; rtPA intravenous thrombolysis is
      frequent; treatment difficulties arise in patients with AF-related CI and a
      history of ICH; the prognosis of VKA-related ICH is poor; the use of oral
      anticoagulants alone or combined with aspirin is controversial in case of AF
      associated with severe atheroma. Patients with AF seen in stroke units are
      therefore very different from those seen by cardiologists: they are older and
      have many vascular risk factors, stroke, and other cerebrovascular lesions,
      raising difficult treatment issues owing to the dual risk of embolic recurrence
      and symptomatic hemorrhagic transformation. In addition, contraindications to
      long-term VKA use are frequent. Many of these issues will again be raised with
      the arrival of new oral anticoagulants.

PMID- 22375366
TI  - [Ten years' experience of preimplantation genetic diagnosis in Paris: remaining
      obstacles and potential solutions].
AB  - Preimplantation genetic diagnosis (PGD) has been authorized in France since 1999.
      Encouraging results have been obtained during the past 10 years in our Paris
      center, where 832 patients have undergone 1056 IVF-PGD procedures. With the
      advent of new techniques for the identification of genetic disease markers, our
      center can now offer PGD procedures for aneuploidy and 75 single-gene diseases.
      New indications for PGD have also been developed, such as mitochondrial DNA
      diseases, amyloid neuropathy, pulmonary arterial hypertension, and HLA typing The
      implantation rate is currently 29,6% and, by 31 December 2009, 151 healthy babies
      had been born. Unfortunately, demand for PGD procedures far outstrips available
      technical capacity, and the waiting period is longer than 18 months. Increased
      funding is urgently needed

PMID- 22375367
TI  - [Extending preimplantation genetic diagnosis to HLA typing: the French
      exception].
AB  - Umut-Talha, a "sibling savior", was born on 26 January 2011 at Beclere Hospital
      after embryo selection at the Paris preimplantation genetic diagnosis (PGD)
      center. His birth revived the controversy over "double PGD". This procedure,
      authorized in France since 2006, allows couples who already have a child with a
      serious, incurable genetic disease, to opt for PGD in order to select a healthy
      embryo that is HLA-matched to the affected sibling and who may thus serve as an
      ombilical cord blood donor. The procedure is particularly complex and the baby
      take-home rate is still very low. Double PGD is strictly regulated in France, and
      candidate couples must first receive individual authorization from the
      Biomedicine Agency. In our experience, these couples have a strong desire to have
      children, as reflected by the large number of prior spontaneous pregnancies (25%
      of couples). Likewise, most of these couples request embryo transfer even when
      there is no HLA-matched embryo, which accounts for more than half of embryo
      transfers. The controversy surrounding this practice has flared up again in
      recent weeks, over the concepts of "designer babies" and "double savior siblings"
      (the baby is selected to be free of the hereditary disease, and may also serve as
      a stem cell donor for the affected sibling).

PMID- 22375368
TI  - [Ethical aspects of preimplantation genetic diagnosis (PGD)].
AB  - The controversy surrounding PGD has not abated in recent times. This is
      especially the case for PGD-based tissue typing, which is used to select a future
      child who could serve as a stem cell donor for an older sick sibling. We examine
      three types of ethical argument cited against PGD in general, and specifically
      against tissue-typing PGD. These arguments focus on the moral status of the early
      embryo, the eugenics issue, and the charge that the future child is being
      exploited. We conclude that none of these three arguments is unassailable, and
      that it is the reproductive freedom of couples considering PGD that should
      prevail.

PMID- 22375369
TI  - [The Laki fog of 1783. Volcanic activity and health crises in Europe].
AB  - Abruptly, in April 2010, airline companies, insurers and politicians discovered
      that volcanic ash from Iceland could disrupt air traffic throughout western
      Europe. Like the Xynthia storm that had hit the west coast of France a few years
      previously, this was a totally "new" and completely unexpected scenario. However,
      archives of the French Royal Society of Medicine preserved in the library of the
      National Academy of Medicine, together with European parochial registers, showed
      that this event was perfectly predictable. Indeed, on 8 June 1783, the Icelandic
      volcano Laki entered an eruptive phase lasting nearly a year, spewing massive
      amounts of smoke which, within hours, was observed in France by correspondents of
      Vicq d'Azyr and by Father Cotte. These "sulfurous fogs", in addition to
      terrorizing the population, were quickly suspected of being harmful to health.
      This fear was amply confirmed by the mortality peak recorded by priests of France
      and Navarre

PMID- 22375370
TI  - [Anatomic correction of transposition of the great arteries: a model of surgical
      "cure" in pediatric cardiology?].
AB  - Transposition of the great arteries (TGA) is a common congenital heart
      malformation, involving inversion of the two great vessels (aorta and pulmonary
      artery). Without surgical treatment, TGA is not compatible with life. The
      prognosis of this malformation has been dramatically changed by the development
      of neonatal cardiac surgery. "Anatomic" repair was introduced in the 1980s, with
      the goal of providing near-normal cardiac anatomy. It is carried out in neonates
      with isolated TGA (so-called simple TGA), as well as in those with associated
      anomalies (ventricular septal defect, aortic coarctation). Since January 1987,
      1020 neonates have undergone anatomic repair of TGA in the pediatric cardiac
      surgery department of Groupe Hospitalier Laennec-Necker-Enfants Malades in Paris.
      The overall mortality rate was 4.8% (49 patients), and all deaths occurred within
      the first postoperative year. Among the 966 survivors who could be monitored
      (mean follow-up 6.2 years), 52 children (5.4%) underwent reoperation, with no
      additional mortality. Nearly all the survivors have normal cardiac function and
      quality of life. Despite significant mortality (albeit currently low) anda low
      risk of reoperation, the mid-term results of anatomic repair of TGA are excellent
      and represent a surgical "cure" in most cases. Very-long-term outcome remains to
      be determined.

PMID- 22375371
TI  - [Role of non-invasive cardiovascular imaging techniques in the evaluation of
      coronary artery disease].
AB  - Several cardiovascular imaging techniques have seen major technical improvements
      in recent years. Visualization of coronary arteries--so important for diagnosis
      and patient management--is routinely performed by coronarography, but new, less
      invasive techniques such as computed tomography are now available. Evaluation of
      myocardial function, which may be impaired in case of myocardial hypoperfusion,
      can now be achieved non invasively by means of echocardiography or scintigraphy.
      New imaging techniques, and MRI in particular, can provide useful complementary
      information. Knowledge of the respective advantages and limitations of these
      techniques is crucial if physicians are to use them appropriately in their daily
      practice, thereby avoiding redundant or useless tests and improving patient
      management.

PMID- 22375372
TI  - [Importance of vitamin D in insulin resistance].
AB  - Beyond its classical role in bone metabolism, fundamental and epidemiological
      studies suggest that vitamin D is also involved in immunity and cell
      proliferation. Indeed, 25-hydroxyvitamin D 1alpha-hydroxylase and specific
      receptors for 1,25-dihydroxyvitamin D, the hormonal form of vitamin D, have been
      found in a variety of organs and tissues, such as the liver, epidermis, thymus,
      small intestine and pancreas. This brief review examines the results of in vitro,
      animal and clinical studies suggesting a role of vitamin D in glucose
      homeostasis. Epidemiological studies and meta-analyses have shown a weak
      association between vitamin D nutritional status and the risk of diabetes, but
      this does not justify the increasing demands for serum vitamin D assay. The
      latter should be restricted to disorders affecting the musculoskeletal system.

PMID- 22375373
TI  - [Biofilms and public health].
AB  - Micro-organisms do not always exist in planctonic forms (single cells or small
      groups). To survive, especially in limiting media, they may adhere to inert or
      living surfaces. This enables them to multiply within a community protected by an
      extracellular matrix, thus forming a biofilm which protects them from
      antimicrobials. Biofilms have many potential consequences for public health. Some
      are positive, such as the commensal biofilms that protect against pathogenic
      bacteria, while environmental biofilms may be a source of outbreaks of
      respiratory or gastrointestinal diseases or infections associated with implanted
      medical devices. Respiratory tract infection can be caused by aerosols of
      fragmented biofilms growing in warm humid conditions (air cooling towers, hot
      springs, showers, etc.). Digestive tract infection can arise from biofilms formed
      during food manufacturing or packaging processes. Colonized implanted medical
      devices can lead to sepsis. This article examines the role of central venous
      catheters, taking into account the surgical site. In vivo studies show that the
      source of catheter infection may be exogenous or endogenous, while in vitro
      studies of biofilms show that ablation of the device is the best solution.
      Prevention is difficult, as biofilm formation is multifactorial. Physical and
      biological knowledge of biofilms may help to limit their formation and growth.

PMID- 22375374
TI  - Nursing journals and the use of technologies such as social networking.

PMID- 22375375
TI  - The graduate nursing workforce: does an international perspective have relevance
      for New Zealand?
AB  - A key focus of concern in relation to the future shape of the nursing workforce
      internationally and nationally has been the perceived high attrition rate of
      graduates. This concern has been accompanied by a plethora of literature on
      graduate transition to practice. Many of the studies have been carried out from
      the perspective of the employing organisation and look at graduates turnover
      intent and retention strategies within the first year of practice. In recent
      years New Zealand has responded with some success to these concerns by
      introducing graduate programmes covering the first twelve months of practice.
      There are fewer published studies that have used local, regional or national
      populations of nursing graduates to explore actual turnover for periods longer
      than the first twelve months transition. This paper reviews these latter studies
      and shows that the most likely reasons for mobility, both within nursing or out
      of the profession, have been found to be related to the work environment and
      family responsibilities. Although some graduates leave the nursing profession
      early in their career, many more have made an employment move within nursing, and
      younger mobile graduates in particular are interested in career promotion. These
      findings suggest that ongoing innovation in roles and skills within the
      professional work context is required to ensure longer term retention of
      graduates. As New Zealand is now collecting graduate nursing workforce data these
      international findings have implications which should be considered in the
      development of New Zealand nursing workforce strategy. Encouraging graduate
      stability depends on a graduate workforce strategy which

PMID- 22375376
TI  - Shaping student nurses' attitudes towards older people through learning and
      experience.
AB  - This paper reports an exploratory New Zealand study comparing student nurses'
      attitudes towards older people before and after an introductory nursing paper
      that included gerontology theory and clinical practice in an aged care setting.
      Health professionals are exposed to ageist attitudes that permeate Western
      societies. Theoretical content and clinical experiences in nursing programmes
      should lead to attitudes that inform the practice of competent and caring
      practitioners. The Kogan Attitudes Towards Old People Scale (1961) was
      administered to 56 student nurses at the beginning and end of the first semester
      of study in a Bachelor of Nursing programme. The results showed a statistically
      significant positive shift in students' self reported attitudes towards older
      people following the integrated theoretical and clinical paper. The findings
      contribute to the international evidence supporting the view that education about
      ageing shapes attitudes when integrated with positive clinical placement
      opportunities.

PMID- 22375377
TI  - Preparing undergraduate nurses to provide smoking cessation advice and help.
AB  - Nurses in New Zealand are expected to provide the Ministry of Health recommended
      ABC approach to smoking cessation interventions; but not all nurses receive
      adequate preparation. A national online survey was conducted to investigate the
      extent that smoking cessation education content is included in undergraduate
      nursing curricula in New Zealand's 17 Schools of Nursing. Fourteen schools
      responded. Of these 12 provide some form of smoking cessation education: five
      teach the recommended ABC approach and seven teach approaches not recommended by
      the Ministry of Health. Nine schools include education about nicotine replacement
      therapy (NRT). In seven schools smoking cessation education was found to be
      fragmented across the curriculum. In the majority of nursing programmes
      preparation of undergraduate nurses to provide smoking cessation advice and help
      is insufficient. It is recommended schools audit and update their curricula to
      include coordinated undergraduate smoking cessation education congruent with
      current national guidelines.

PMID- 22375378
TI  - Young tertiary students and help-seeking for health advice.
AB  - Help-seeking is an active process used by people of all ages to obtain assistance
      to solve problems. This research sought to investigate a component of help
      seeking related to health concerns. A health related help-seeking model, was
      adapted to frame questions for an anonymous, self-administered questionnaire.
      Seventy-five students aged between 16 and 24 years responded and data were
      analysed using content and descriptive statistical techniques. Findings indicated
      that young people perceived the need to seek advice when unwell, needing support
      or information, are resourceful, and were motivated to seek help from a variety
      of sources. Parents and whanau formed one usual source of advice, but young
      people reported one of the best sources of advice as General Practice nurses and
      doctors. Barriers to seeking advice included distrusting sources, and concerns
      about confidentiality. Unsurprisingly, many respondents used the Internet for
      health information, although some mistrusted that information. Nurses need to be
      aware of the sources of health advice and support that young people choose to
      use. Motivations for selecting services, providers, or sources clearly replicated
      what young people hold as important--sources with which they feel comfortable,
      have a relationship, trust, and which they perceived as maintaining
      confidentiality.

PMID- 22375379
TI  - [Effect of enhanced UV-B radiation on metabolism and berberine content of Coptis
      chinensis].
AB  - OBJECTIVE: To reveal the response of content berberine in root of Coptis
      chinensis to different intensity of UV-B radiation, and provide the theory basis
      for promoting the content of berberine. METHOD: Four groups of UV-B radiation
      were set in the experiment which included: natural light control (0 W x m(-2)),
      UL (0.05 W x m(-2)), UM (0.10 W x m(-2)), UH (0.20 W x m(-2)). The special
      photosynthesis character, PPP pathway in the primary metabolism and lyrosinase
      activity, the changes of berberine in the root of C. chinensis were measured
      under different UV-B radiation. RESULT: Photosynthetic pigment, qN, Fo, ETR,
      activity of glucose-6-phosphate dehydrogenase and the content of berberine in the
      root of C. chinensis, all of these parameters were lower than other groups under
      the UH radiation. However, under the UM radiation, C. chinensis protected itself
      from the light UV-B radiation by promoting the power of photosynthesis and PPP
      pathway in order to produce more NADPH and secondary metabolites. CONCLUSION: C.
      chinensis increases its photosynthetic ability and PPP pathway which can furnish
      more precursor of secondary metabolites and NADPH that are needed in the
      secondary metabolism. Furthermore, the content of berberine increases
      correspondingly. The research provide the example for increasing the content of
      berberine in C. chinensis cultivation.

PMID- 22375380
TI  - [Study on content and distribution characteristics of mineral elements from
      cultivated and wild Prunella vulgaris].
AB  - OBJECTIVE: The contents of mineral elements in soil and each organ from
      cultivated and wild Prunella vulgaris were determined in order to provide a
      theoretical basis for exploitation and protection of wild resources and GAP
      study. METHOD: The contents of mineral elements (P, K, Ca, Mg, Na, Fe, Cu, Zn,
      Mn, Al) in soil and each organ from cultivated and wild P. vulgaris were
      determined by ICP-AES, and the results were analyzed by correlation analysis.
      RESULT: The contents of mineral elements in soil and different organs of P.
      vulgaris were significant different between cultivated and wild species; the
      contents of P and Cu ranked in the order of spica > leaf > stem, the order of Mg,
      Ca, Zn, Fe, Mn, Al from high to low was leaf > spica > stem, the concentrations
      of K, Na were mainly distributed in leaf and stem, less in spica. A distinctly
      positive correlation between soil and spica for Fe content, and the relationship
      between soil and leaf, stem were significant positive correlation, the
      concentrations of Zn in spica, leaf, stem were positively related to soil, K
      contents in soil and stem were significant positive correlation. The different
      organs of cultivated and wild P. vulgaris had a strong tendency to accumulate P.
      CONCLUSION: There was no direct relationship between the concentrations of
      mineral elements in P. vulgaris, and their corresponding soil P. vulgaris adjusts
      the concentration of mineral elements mainly by active absorption.

PMID- 22375381
TI  - [Study on electrophoretogram of Magnolia officinalis seeds from different
      locations].
AB  - OBJECTIVE: To find the identification method of seeds from different locations,
      we analyzed the SDS-PAGE electrophoretogram of Magnolia officinalis seeds from 5
      different locations of Enshi district, Hubei province, the genuine producing area
      of M. officinalis, and compared band numbers, band intensity and protein
      molecular weight of different locations. The result showed that there were
      significant differences among seeds from different locations. 9 bands with the
      molecular weight about 80.34, 63.07, 56.48, 51.32, 40.64, 25.18, 22.63, 21.70,
      18.14 kDa were involved in all seeds electrophoretograms and could be as standard
      bands of M. officinalis seeds. Seeds from Badong county, Jianshi county and Enshi
      city had their own special bands which were very different from other locations.
      So this electrophresis method can be applied to identify different locations of
      M. officinalis seeds.

PMID- 22375382
TI  - [Pollen viability and stigma receptivity of Angelica dahurica from Sichuan and
      Hebei province].
AB  - OBJECTIVE: To provide theoretical basis for artificial cross breeding of Angelica
      dahurica from Sichuan and Hebei Province, the characteristics of stigma
      receptivity and the viability and life-span of pollen were studied. METHOD: The
      viability and life-span of pollen were evaluated by TTC (2, 3, 5-triphenyl
      tetrazlium chloride) test, and the stigma receptivity was estimated by benzidine
      H2O2 method. RESULT: The pollen viability of A. dahurica from Sichuan and Hebei
      provinces was increased gradually since the bud stage, but those levels had since
      subsided after the pollen release from craze antheral. There was a little
      difference in the pollen viability of A. dahurica from Sichuan at different
      branches. While the order of the pollen viability of A. dahurica from Hebei was
      main stem < first-order branching < second-order branching. At room temperature,
      the pollen viability of both decreased during time of anthers dehiscing but also
      above 50% after 5 days. Compared with 4 degrees C and room temperature,
      conservation at - 20 degrees C could extend life of the pollen. The stigma had
      receptivity in 4th day and reached the highest level in the 6th day after
      blooming. CONCLUSION: The optimum artificial pollination times of A. dahurica was
      6 days after blooming and choose the pollen in the peak stage of anthers
      dehiscing.

PMID- 22375383
TI  - [Identification of Schisandra sphenanthera and S. chinensis by random amplified
      polymorphic DNA sequence characterized applied region].
AB  - OBJECTIVE: To establish a new method for the identification of Schisandra
      sphenanthera and S. chinensis. METHOD: Random amplified polymorphic DNA-Sequence
      characterized applied region (RAPD-SCAR) method was applied to screen primers.
      RESULT: Screening from 100 primers, only 2 random primers, which can be used to
      identify S. sphenanthera and S. chinensis accurately with a good reproducibility.
      It worked to fit them into sequence characterized applied region. CONCLUSION:
      RAPD-SCAR can be used to identify S. sphenanthera and S. chinensis accurately.

PMID- 22375384
TI  - [Testing methods for seed quality of Amomum villosum].
AB  - OBJECTIVE: The aim of this study was to optimize the testing methods for seed
      quality, and to provide a basis for establishing seed testing criterion and
      quality standard of Amomum villosum. METHOD: Referring to the International Seed
      Testing Rules made by ISTA and Rules for agricultural seed testing, the seed
      quality of A. villosum from different collection areas was measured. RESULT: The
      samples weight of A. villosum for purity analysis were at least 500 g and for
      test were at least 50 g. Verification of genuineness was assayed by seed
      appearance comparing and weight of per hundred seeds was determined, the moisture
      content test was carried out by high temperature drying method (3 hours). The
      seeds were stored in wet sand for 20 days and then dipping in the 100 mg x L(-1)
      GA3 for 30 days before germination, seeds on filter papers germinated at 30/20
      degrees C. The first germination-counting time was the 15th day of the test and
      the final time was the 50th day. Seed viability was tested by TTC method.
      CONCLUSION: The seed testing methods for quality items of A. villosum, including
      sampling, purity analysis, verification of genuineness, weight, moisture content,
      percentage germination and seed viability of A. villosum had been initially
      established.

PMID- 22375385
TI  - [Study on correlations between total saponins content in rhizome or mycorrhizal
      infection rate of Pairs polyphylla var. yunnanensis and soil factors].
AB  - OBJECTIVE: Through correlation and path analysis between total saponins content
      in rhizome/mycorrhizal infection rate in roots of Pairs polyphylla var.
      yunnanensis and soil factors, to make an inquiry into the role of soil factors in
      the quality formation of P. polyphylla var. yunnanensis. METHOD: Tested total
      saponins in rhizome, mycorrhizal fungal infection rate in root and physical and
      chemical properties in rhizosphere soil in 25 different growth areas, and
      statistically analyzed the relationship between total saponins in
      rhizome/mycorrhizal infection rate in roots of P. polyphylla var. yunnanensis and
      soil factors by using correlation and path analysis. RESULT: The symbiosis
      relationship between AM mycorrhizal and roots of P. polyphylla var. yunnanensis
      were better established under natural condition, of which the infection ratio
      between 36.41%, 83.37%. There were significantly positive correlation between
      total saponins content in rhizome and urease activity or alkaline phosphatase
      activities or organic matter in soil, but there was significantly negative
      correlation between total saponins content and bulk density. There was
      significantly positive correlation between AM infection ratio and alkaline
      nitrogen. Path analysis indicated that total saponins of rhizome mainly affected
      by alkaline nitrogen in soil rhizosphere, secondly by soil organic matter and
      soil urease activity. While the mycorrhizal fungal colonization ratio was mainly
      affected by soil pH, secondly by alkaline nitrogen, urease activity, and
      available phospherus in soil. CONCLUSION: There is closed relationship between
      quality formation of P. polyphylla var. yunnanensis and soil factors. Path
      analysis is better for reflecting the contribution of soil factors to total
      saponins and mycorrhizal infection ratio.

PMID- 22375386
TI  - [Mathematic modeling and experimental validation of macrostate quality expression
      for multicomponent in Chinese materia medica].
AB  - OBJECTIVE: To establish the unitive multicomponent quality system bridged
      macrostate mathematic model parameters of material quality and microstate
      component concentration for Chinese materia medica (CMM). METHOD: According to
      law of biologic laws of thermodynamics, the state functions of macrostate qulity
      of the CMM were established. The validation test was carried out as modeling drug
      as alcohol extract of Radix Rhozome (AERR), their enthalpy of combustion was
      determined, and entropy and the capability of information by chromatographic
      fingerprint were assayed, and then the biologic apparent macrostate parameters
      were calculated. RESULT: The biologic macrostate mathematic models, for the CMM
      quality controll, were established as parameters as the apparent equilibrium
      constant, biologic enthalpy, Gibbs free energy and biologic entropy etc. The
      total molarity for the 10 batchs of AERR were 0.153 4 mmol x g(-1) with 28.26% of
      RSD, with the average of apparent equilibrium constants, biologic enthalpy, Gibbs
      free energy and biologic entropy were 0.039 65, 8 005 J x mol(-1), -2.408 x 10(7)
      J x mol(-1) and - 8.078 x 10(4) J x K(-1) with RSD as 6.020%, 1.860%, 42.32% and
      42.31%, respectively. CONCLUSION: The macrostate quality models for CMM can
      represent their intrinsic quality for multicomponent dynamic system such as the
      CMM, to manifest out as if the forest away from or tree near from to see it.

PMID- 22375387
TI  - [USMM technology application in extraction and separation of Salvia
      miltiorrhiza].
AB  - OBJECTIVE: To investigate USMM coupled techniques applied in active ingredient
      extraction and separation of Salvia. METHOD: Supercritical fluid extraction (SFE)
      CO2 was used to extract and separate tanshinone liposoluble constituent,
      ultrasonic was used to extract danshen phenolic acids ternate, membrane
      separation and macroporous resin was used to purify water extraction from HDP.
      Transfer rate and purity of Danshen active ingredients were employed as the
      investigation indexes, the feasibility of USMM technology used in extraction and
      separation S. miltiorrhiza was investigated. RESULT: SFE-CO2 extraction process
      for S. miltiorrhiza was stable and feasible. Danshen phenolic acids extracted
      from slag of SFE-CO2 by ultrasound got a high yield. Macroporous resin
      purification technology could improve the purity of active ingredients of S.
      miltiorrhiza. Membrane separation and membrane separation coupled with
      macroporous resin technology applied to the purification process of S.
      miltiorrhiza phenolic acids still needed further research. CONCLUSION: It is
      feasible basically that USMM technology apply in extraction and separation of
      Salvia active ingredient.

PMID- 22375388
TI  - [Alcohol-purification technology and its particle sedimentation process in
      manufactory of Fufang Kushen injection].
AB  - OBJECTIVE: Fufang Kushen injection was selected as the model drug, to optimize
      its alcohol-purification process and understand the characteristics of particle
      sedimentation process, and to investigate the feasibility of using process
      analytical technology (PAT) on traditional Chinese medicine (TCM) manufacturing.
      METHOD: Total alkaloids (calculated by matrine, oxymatrine, sophoridine and
      oxysophoridine) and macrozamin were selected as quality evaluation markers to
      optimize the process of Fufang Kushen injection purification with alcohol.
      Process parameters of particulate formed in the alcohol-purification, such as the
      number, density and sedimentation velocity, were also determined to define the
      sedimentation time and well understand the process. RESULT: The purification
      process was optimized as that alcohol is added to the concentrated extract
      solution (drug material) to certain concentration for 2 times and deposited the
      alcohol-solution containing drug-material to sediment for some time, i.e. 60%
      alcohol deposited for 36 hours, filter and then 80% -90% alcohol deposited for 6
      hours in turn. The content of total alkaloids was decreased a little during the
      depositing process. The average settling time of particles with the diameters of
      10, 25 microm were 157.7, 25.2 h in the first alcohol-purified process, and 84.2,
      13.5 h in the second alcohol-purified process, respectively. CONCLUSION: The
      optimized alcohol-purification process remains the marker compositions better and
      compared with the initial process, it's time saving and much economy. The
      manufacturing quality of TCM-injection can be controlled by process. PAT pattern
      must be designed under the well understanding of process of TCM production.

PMID- 22375389
TI  - [Analysis of chemical composition of sini san by ultra performance liquid
      chromatography-electrospray ionization-mass spectrometry].
AB  - OBJECTIVE: To analyze and identify the chemical ingredients in Sini San by LC-MS.
      METHOD: These compounds were analyzed with an ACQUITY UPLC BEH C18 (2.1 mm x 100
      mm, 1.7 microm) by gradient elution of methyl cyanides and 0.1% formic acid. ESI
      source was used and data were collected in positive and negative mode. RESULT:
      Seventeen compounds of Sini San were identified by direct comparison in both
      positive and negative modes of Q-TOF-MS, the elemental compositions analysis, the
      standard substance and the data of the literature. CONCLUSION: It is a rapid and
      accurate method that the composition of compound prescription of traditional
      Chinese medicine can be identified in terms of the separation of ultra high
      performance liquid chromatography, the accurate molecurlar weights measured by MS
      and other information, which can trace to the source of compounds in Sinisan.

PMID- 22375390
TI  - [Study on double fingerprints of isatidis radix micropowder].
AB  - OBJECTIVE: To establish the double HPLC fingerprints of water-soluble composition
      and amino acids precolumn derivative reagent of 13 batches of Isatidis Radix
      micropower. METHOD: The gradient elution was adopted with Hypersil BDS C18 column
      (4.6 mm x 250 mm, 5 microm). Water-soluble ingredients were detected with
      acetonitrile-0.1% phosphoric acid solution as mobile phase, flow rate 0.5 mL x
      min(-1), column temperature 20 degrees C, and the injection volume 10 microL.
      Amino acid ingredient were derived by PITC, and then were detected with mobile
      phase of 0.1 mol x L(-1) sodium acetate buffer solution (pH 6.5) - acetonitrile,
      flow rate 1.0 mL x min(-1), column temperature 30 degrees C, and the injection
      volume 5 microL. Both of the absorption wavelengths were 254 nm. Pharmacopoeia
      Commission "Chinese chromatographic fingerprint evaluation system (version 2.0)"
      was adopted to analyse, fingerprints of Isatidis Radix micropower were
      established, at the same time 4 main ingredients were recognized by the SPSS
      cluster analysis. RESULT: Common mode of Fingerprint to water-soluble and amino
      acids ingredient of Isatidis Radix micropower was established, then adenosine,
      epigoitrin and 15 amino acids were identified as characteristic peaks. Cluster
      analysis showed that different kinds of the herbal Isatidis Radix micropower from
      different areas were different levels in the main ingredients. CONCLUSION: Double
      fingerprints of Isatidis Radix micropower is established. Each peak is optimally
      separated in chromatogram, which provides a scientific basis for quality control
      of Isatidis Radix micropower.

PMID- 22375391
TI  - [Chemical constituents from Rehmannia glutinosa].
AB  - OBJECTIVE: To study the chemical constituents from the roots of Rehmannia
      glutinosa. METHOD: The compounds were isolated by various chromatographic methods
      and identified by spectroscopic analysis. RESULT: Twelve compounds were isolated
      and their structures were identified as 5-hydroxymethyl-pyrrole-2-carbaldehyde
      (1), 5-hydroxymethyl furfural (2), tyrosol (3), 5,6-dihydroxy-beta-ionone (4), 6
      O-E-feruloyl ajugol (5), acteoside (6), leucosceptoside A (7), martynoside (8),
      isomartynoside (9), purpureaside C (10), jionoside A1 (11), and jionoside B1
      (12). CONCLUSION: Compounds 1, 3 and 9 were isolated from the genus Rehmannia for
      the first time.

PMID- 22375392
TI  - [Study of flavonoids from leaves of Santalum album].
AB  - OBJECTIVE: To study the flavonoids from the leaves of Santalum album. METHOD: The
      sample was extracted with 70% ethanol by continuous thermal reflux. The
      extraction was separated and purified by column chromatography over macroporous
      adsorption resin, polyamide and sephadexlh-20. Their structures were identified
      by detailed spectroscopic analysis. RESULT: Eight flavonoids were isolated and
      identified as vicenin-2 (1), vitexin (2), isovitexin (3), orientin (4),
      isoorientin (5). chrysin-8-C-beta-D-glucopyranoside (6), chrysin-6-C-beta-D
      glucopyranoside (7), and isorhamnetin (8). CONCLUSION: All compounds were
      isolated from this plant for the first time.

PMID- 22375393
TI  - [Chemical studies on alkaloids of Chinese medicinal herbs Daphniphyllum
      macropodum].
AB  - OBJECTIVE: To study the alkaloids of the Chinese medicinal herbs Daphniphyllum
      macropodum for in search for new bioactive substances. METHOD: The CHCl3 extract
      of D. macropodum was subjected to repeated column chromatography on silica gel to
      afford four pure compounds (1-4). Their structures were determined on the basis
      of detailed spectroscopic analysis and comparison with the data reported in the
      literature. RESULT: The four known compounds were isolated and elucidated as
      Daphniphyllum alkaloids with different carbon skeletons, namely
      longistylumphylline A (1), deoxycalyciphylline B (2), daphnicyclidin B (3) and H
      (4), respectively. CONCLUSION: All compounds were isolated from the titled plant
      for the first time. The discovery of daphnicyclidin B (3) and H (4) further
      confirmed the biogenetic relationship between the two compounds and the
      previously reported macropodumines A-C, found in the same plant.

PMID- 22375394
TI  - [Simultaneous determination of four acids active compounds in Erodium
      stephanianum by RP-HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the determination of four acids
      compounds including gallic acid, protocatechuic acid, corilagin and ellagic acid
      in Erodium Stephanianum. METHOD: The RP-HPLC separation was performed on an
      Agilent TC-C18 analytical column (4.6 mm x 250 mm, 5 microm). The mobile phase
      was methanol (A) -water containing 0.4% H3PO4 (B) with gradient elution mode at
      the flow rate of 0.8 mL x min(-1). The detection wavelength was set at 259 nm,
      and the column temperature was 30 degrees C. RESULT: The liner ranges of gallic
      acid, protocatechuic acid, corilagin and ellagic acid were 0.059-2.360 g x L(-1)
      (r = 0.999 6), 0.017-0.672 g x L(-1) (r = 0.999 9), 0.351-14.040 g x L(-1) (r =
      0.999 9), and 0.151-6.040 g x L(-1) (r = 0.999 8), respectively. The average
      recoveries (n = 3) were 99.45% (RSD 1.5%), 98.65% (RSD 1.7%), 100.3% (RSD 2.0%),
      and 98.90% (RSD 1.2%), respectively. CONCLUSION: The method is simple and
      accurate with a good reproducibility and can be used for quality control of
      Erodium stephanianum.

PMID- 22375395
TI  - [Simultaneous determination of seven compounds in flowers of Polygonum orientale
      by ultra performance liquid chromatography coupled with photo diode array
      detection].
AB  - To establish a UPLC method for simultaneous determination of seven chemical
      markers (gallic acid, catechin, alphitonin, taxifolin, kaempferol-3-O-beta-D
      glucoside, quercetin-3-O-alpha-L-rhamnoside, and kaempferol-3-O-alpha-L
      rhamnoside) of the flowers of Polygonum Oriental collected from Guizhou province.
      Separation was performed at 45 degrees on a ACQUITY UPLC BEH C18 column (2.1 mm x
      150 mm, 1.7 microm) with a gradient solvent system of 0.1% formic acid in
      acetonitrile-0.1% aqueous formic acid as the mobile phase. The flow rate was 0.3
      mL x min(-1), the detection wavelength was 280 nm, and the sample injection
      volume was 1 microL. In the selected linear range, all calibration curves of the
      seven chemical markers showed good linearity. The recoveries (n = 6) were in the
      range of 97.90% -101.4% and RSD were less than 3.8%. The results showed that the
      seven compounds contained in all the samples of the flowers of P. orientale can
      be chosen as their chemical markers and that this UPLC-PAD method is simple,
      reliable and suitable for the quality control of the flowers of P. orientale.
      However, the chemical markers may be present at different levels for samples
      collected in different areas and at different times. A collection time of mid-to
      late August with relatively high content of the chemical markers was suggested
      for the flowers of P. orientale.

PMID- 22375396
TI  - [Determination of tortoside A in Ilicis pubescentis by RP-HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the determination of tortoside A in
      Ilex pubences. METHOD: Kromasil-C18 (4.6 mm x 250 mm, 5 microm) column was used
      in HPLC with mobile phase acetonitrite-0.1% H3PO4 (17:83), the column temperature
      was 30 degrees C, the flow rate was 1 mL x min(-1), the detection wavelength was
      set at 210 nm, and inject volume was 10 microL RESULT: Tortoside A was well
      separated under the established conditions, the liner range of tortoside A was
      26.05-521.00 microg (r = 0.999 9, n = 6), and the average recovery was 98.42%.
      CONCLUSION: It was the first time to establish the RP-HPLC method with accuracy,
      good reproducibility for determining the content of tortoside A in I.
      Pubescentis.

PMID- 22375397
TI  - [Chemical composition and antibacterial activity of the essential oil from leaves
      of Chimonanthus grammatus].
AB  - The chemical composition of essential oil, which from the leaves of Chimonanthus
      grammatus obtained by hydrodistillation were analyzed by GC-MS, and their
      possible antibacterial properties were screened. According to the results from GC
      MS analysis, fifty-three components comprising 99.99% of the essential oil were
      identified. The major components of essential oil were 3-(4, 8-dimethyl-3,7
      nonadienyl)(E) -furan (13.1%), bornyl acetate (12.66%), and 6,6-dimethyl-3
      methylene-bicyclo[3.1.1] heptane (7.06%), etc. Antibacterial activity of
      essential oil was employed by two complementary test systems of disc diffusion
      and MIC/ MBC tests, which showed obviously antibacterial activity against all of
      the tested bacteria.

PMID- 22375398
TI  - [Anti-inflammation effect of danggui shaoyao san on Alzheimer's diseases].
AB  - OBJECTIVE: To study the mechanisms of Danggui Shaoyao San (DSS) on Alzheimer's
      diseases (AD) focusing on anti-inflammation. METHOD: AD rats were established by
      intrahippocampal bilateral injection of Abeta1-42 protein. The AD rats were
      randomly divided into three groups: AD model group, DSS high-dose group, DSS low
      dose group. Vehicle group rats were intrahippocampal bilateral injection of
      solvent with the same dose. The learning ability and memory of rats was
      investigated in step-down passive avoidance test and Morris water maze test,
      expression of IL-1beta, IL-6, TNF-alpha mRNA were observed by reverse
      transcriptase PCR (RT-PCR), levels of NO was measured by colorimetric method and
      neuron apoptosis in the hippocampus was investigated by tag method of TdT
      mediated end-labeling of fragmented DNA (TUNEL). RESULT: DSS significantly
      reduced the escape latency and increased the time that rats spent in the target
      quadrant in Morris water maze test, shortened the responsive latency and
      decreased the error numbers in step-down passive avoidance test, reduced the
      expression of the IL-1beta, IL-6, TNF-alpha mRNA, and the level of the NO
      depressed the neuron apoptosis in the hippocampus. CONCLUSION: DSS improving
      cognition of the rats might be related to attenuate inflammatory reaction and
      reduce cell apoptosis in the hippocampus.

PMID- 22375399
TI  - [Identify nature N-acylethanolamide-hydrolyzing acid amide (NAAA) inhibitor:
      effect of angelicae pubescentis radix on anti-inflammation].
AB  - OBJECTIVE: To investigate the effect of Angelicae Pubescentis Radix (APR) on the
      activity of endocannabinoid hydrolase and N-acylethanolamine-hydrolyzing acid
      amidase (NAAA), and to demonstrate the mechanism of anti-inflammatory effect of
      APR by in vitro lipopolysaccharide (LPS)-induced inflammation model. METHOD: APR
      essential oil was extracted by steam distillation, and the chemical components
      were identified by GC-MS. Enzymatic activity was performed by using recombinant
      NAAA-overexpressing protein and detected by LC-MS. Lipids were extracted by
      methonal/chloroform mixure and analyzed by LC-MS. mRNA and protein expression
      levels of proinflammatory genes were examined by Real time-PCR and ELISA assay
      kit, respectively. The content of nitro oxide (NO) was detected by Griess
      reaction. RESULT: Twenty active components were identified from APR essential oil
      which inhibited NAAA activity in a dose-dependent manner. On the LPS-induced
      RAW264.7 cells, APR essential oil reversed LPS-suppressed N-palmitoylethanolamide
      (PEA) contents in a dose-dependent manner and reduced LPS-induced proinflammatory
      genes, TNF-alpha and IL-6. Moreover, APR essential oil reduced the mRNA
      expression of iNOS, subsequently reduced the release of NO, a classic
      inflammatory marker. CONCLUSION: The research demonstrated that the effect of APR
      on inflammation is mediated by the inhibition of NAAA activity, which increase
      the cellular endobioactor PEA levels and decrease proinflammatory factor. The
      results suggest that APR can serve as a nature NAAA inhibitor.

PMID- 22375400
TI  - [Experimental study on anti-metastasis effect of emodin on human pancreatic
      cancer].
AB  - OBJECTIVE: To investigate the anti-metastasis effect of emodin on the pancreatic
      cancer in vitro and in vivo. METHOD: Human pancreatic cancer cell line SW1990 was
      treated with different concentrations of emodin (10, 20, 40 micromol x L(-1)) for
      2 h, the effects of emodin on the migration and invasion of SW1990 cells were
      examined by using wound assay and matrigel counting. Western blot was used to
      detect the protein expression of NF-kappaB and MMP-9 in SW1990 cells after
      various concentrations of emodin (10, 20, 40 micromol x L(-1)) treatment for 48
      h. Metastatic model simulating human pancreatic cancer was established by
      orthotropic implantation of histologically intact human tumor tissue into
      pancreatic wall of nude mice, and then divided into three groups: control group,
      low-dose emodin group (L-EMO) and high-dose emodin group (H-EMO). Eight weeks
      after implantation, the presences of metastasis were evaluated respectively after
      the mice were sacrificed. Immunohistochemistry was used to detect the positive
      expression of CD34, NF-kappaB and MMP-9 in the tumors. RESULT: Emodin suppressed
      the migration and invasion of SW1990 cells in a dose-dependent manner. Western
      bolt assay indicated that emodin down-regulated the expression of NF-kappaB and
      MMP-9 proteins in SW1990 cells. The incidences of metastasis were decreased
      significantly in L-EMO group and H-EMO group as compared with that in control
      group. The percentage of CD34, NF-kappaB and MMP-9-positive cells in the tumors
      were significantly reduced by the administration of emodin. CONCLUSION: Emodin
      exerts anti-metastatic activity in pancreatic cancer both in vitro and in vivo,
      which may be related to down-regulation of NF-kappaB and MMP-9.

PMID- 22375401
TI  - [Changes of telomere and telomerase in effect of ginsenoside Rg1 to delay
      hematopoietic stem cell senescence].
AB  - OBJECTIVE: To investigate the roles of telomere and telomerase in the effect of
      ginsenoside Rg1 to delay hematopoietic stem cell senescence. METHOD: Sca-1(+) HSC
      was isolated by magnetic cell sorting(MACS) and divided into five groups: the
      control group, the aged model group, the Rg1 group, the Rg1 treated aged group
      and the Rg1 delayed aged group. The changes of cells were observed by senescence
      associated beta-Galactosidase (SA-beta-Gal) staining. Cell cycle assay and
      culture of mixed hematopoietic progenitor cell were used to investigate the
      effect of ginsenoside Rg1 to delay Sca-1(+) HSC senescence. Telomere length and
      telomerase activity were detected by southern blotting and TRAP-PCR-SYBR Green
      staining. RESULT: Compared with aged model group, the percentage of positive
      cells expressed SA-beta-Gal and the number of cells entered G1 phase were
      decreased and the number of colony of mixed hematopoietic progenitor was
      increased. It showed markedly decreased in the shortening of telomere length and
      reinforcing in the telomerase activity to Rg1 treated aged group and Rg1 delayed
      aged group. The change of Rg1 delayed aged group was significantly higher than
      Rg1 treated aged group. CONCLUSION: Activation of telomerase and prolonging of
      telomere length might be involved in the process of ginsenoside Rg1 to delay and
      treat the senescence of Sca-1(+) HSC.

PMID- 22375402
TI  - [Effect of compatibilities and proportions of shuanglong formula on acute
      myocardial infarction in rats].
AB  - OBJECTIVE: To verify the rational of Chinese medicine Shuanglong formula. METHOD:
      Rat models of acute myocardial ischemia were induced by hydrochloride
      isoproterenol. ECG J point change, myocardial infarction area and cellular enzyme
      (CK, LDH, SOD and MDA) levels were observed and detected to show protective
      effect of treatment groups. RESULT: The single drug prescriptions and
      compatibilities both could improve ECG performance, decrease levels of CK, LDH,
      SOD and MDA in serum, and reduce a certain myocardial infarct size. CONCLUSION:
      The Shuanglong formula at the high dose of 3:7 was proved to be more effective on
      myocardial ischemia.

PMID- 22375403
TI  - [Effect of single-used borneol and combining it with diazepam on content of
      neurotransmitter in corpus striatum of rats].
AB  - OBJECTIVE: To research the content changes of excitatory neurotransmitter and
      inhibitory neurotransmitter in corpus striatum of rats after single-used borneol
      and combining it with diazepam in hope of comprehending the activity of borneol
      on central nervous system and to observe whether borneol could increase the
      penetration of other drugs into the brain. METHOD: The content of four amino
      acids neurotransmitters in corpus striatum of rats were sampled by brain
      microdialysis technology at different time after administration and were
      determined by RP-HPLC which involved pre-column derivation with
      orthophthaladehyde (OPA), using phosphate gradient elution and fluorescence
      detection to detect the content of excitatory neurotransmitter aspartate (Asp),
      glutamate (Glu) and inhibitory neurotransmitter glycine (Gly), gamma-aminobutyric
      acid (GABA) in standards and samples and carry on statistical analysis. RESULT:
      The content of both Gly and GABA in corpus striatum of rats with borneol
      increased significantly, compared with diazepam group (P < 0.05), while Asp and
      Glu showed no significant difference. CONCLUSION: Borneol can improve
      permeability of diazepam through BBB.

PMID- 22375404
TI  - [Research of herb components on scavenging harmful components and reducing
      cytotoxicity of cigarette smoke].
AB  - OBJECTIVE: To study the in vitro effect of herb components on scavenging harmful
      components of cigarette smoke such as radicals, polycyclic aromatic hydrocarbons,
      nitrosamines in vitro, and its reducing effect on cytotoxicity of cigarette
      smoke. METHOD: spectrophotometry was used to examine the scavenging effect of
      herb components on DPPH free radicals, superoxide anion radical, and hydroxyl
      radical, and the results were compared with the anti-oxidation of ascorbic acid.
      Fluorescence spectroscopy was used to examine the scavenging effect of herb
      components on polycyclic aromatic hydrocarbons. UV spectrophotometry was used to
      examine the scavenging effect of herb components on volatile nitrosamines. MTT
      assay was used to examine cytotoxicity of cigarette smoke. RESULT: All the herb
      components showed a certain scavenging effect on DPPH free radicals, superoxide
      anion radical, hydroxyl radical, polycyclic aromatic hydrocarbons and volatile
      nitrosamines, espacially the ginkgo biloba extract (GBE), flavonoids of
      glycyrrhiza, procyanidine, total saponins in ophiopogonin, total saponins of
      astragalus and epimediun flavonoids. After these six herb components were added
      to cigarette, the cytotoxicity of cigarette smoke on BEP2D cells was remarkably
      reduced, by increasing cell survival fraction (SF, %) and mean lethal dose (DML).
      CONCLUSION: The herb components can scavenge harmful components of cigarette
      smoke such as radicals, polycyclic aromatic hydrocarbons and nitrosamines, which
      reduce the damage of cigarette smoke on human being.

PMID- 22375405
TI  - [Simultaneous determination of protocatechuic acid, isoorientin and scutellarin
      in rat tissues after a single intravenous administration of compound hongcao for
      injection by UPLC-MS/MS].
AB  - OBJECTIVE: To establish an UPLC-MS/MS method for simultaneous determination
      protocatechuic acid, isoorientin and scutellarin in rat tissues after a single
      intravenous administration of Compound Hongcao for injection, and investigate the
      distribution character of the three compounds. METHOD: Three compounds were
      simultaneously determined by UPLC with Waters Acquity UPLC BEH C18 column. The
      mobile phase, consisting of acetonitrile and 0.1% aqueous formic acid, was
      programmed as a linear gradient. The flow rate was 0.35 mL x min(-1). The
      compounds were ionized in the electrospray ionization ion source of the mass
      spectrometer and detected in the multiple reaction model. The tissue samples were
      homogenated and the suspension were extracted with methanol for further use.
      RESULT: The relationship between the concentration and the peak areas of the
      three compounds were all linear (r > 0. 99). The precisions, accuracy, extract
      recoveries and stability of the analytes meet the requirements. The method has
      been successfully applied to tissue distribution studies of the three compounds.
      The present study demonstrates that the higher tissues concentration of three
      components were obtained in kidney, lung and heart after a single intravenous
      administration of ones. CONCLUSION: The present study demonstrates that the three
      compounds have unequal distribution character. It was showed that the three
      compounds were mainly distributed in abundant blood-supply tissues such as
      kidney, lung and heart. It was also found that protocatechuic acid, isoorientin
      and scutellarin exceretion rapidly and have no long-term accumulation. The method
      was shown to be effective, convenient, and suitable for simultaneous study the
      distribution of the three compounds in rat.

PMID- 22375406
TI  - [Pharmacokinetics study of compound xueshuantong soft capsules].
AB  - OBJECTIVE: To establish a RP-HPLC method for determination of the content of
      ginsenoside Rg1 in the rabbits aqueous humor, blood and ocular tissues, which
      were given intragastric administration with the co-xueshuantong soft capsules.
      The drug concentration in rabbits at different times after oral administration
      has been determined and the pharmacokinetics characteristics has been researched.
      METHOD: The compound xueshuantong soft capsules were administrated to the healthy
      New Zealand rabbits by gavage (10 mg x kg(-1) per rabbit). The concentration of
      Ginseng Rg1 in aqueous humor, blood and ocular tissues at different time was
      determined by RP-HPLC. RESULT: RP-HPLC can be established for the determination
      of ginsenoside Rg1 in the rabbits aqueous humor, blood, ocular tissue. The
      calibration of curves was linear within the range of 7.60-152.0 mg x L(-1) (r =
      0.999 6) for ginsenoside Rg1 in aqueous humor and the calibration of curves were
      linear within the range of 10.35-103, 50 mg x L(-1) (r = 0.999 8) for ginsenoside
      Rg1 in blood. Determination of the recovery rate to meet the requirements.
      CONCLUSION: The ginsenosides Rg1 could transmit the blood-ocular barrier into the
      eyes and reach a certain concentration. The research provides a theoretical and
      experimental basis for the systemic administration of compound Xueshuantong to
      treat eye diseases.

PMID- 22375407
TI  - [Meta analysis of compound matrine injection combined with cisplatin chemotherapy
      for advanced gastric cancer].
AB  - OBJECTIVE: To assess the efficacy and safety of compound matrine injection
      combined with cisplatin chemotherapy for advanced gastric cancer. METHOD: It was
      searched relevant randomized Controlled trials (RCTs) from Cochrane Library,
      PubMed, EMBASE, CBM, and CNKI etc. The search was finished in February 11, 2010.
      And it was traced the related references and experts in this field, besides it
      was also communicated with other authors in order to obtain some certain
      information that had not been found. RCTs of compound matrine injection combined
      with cisplatin chemotherapy versus cisplatin chemotherapy for advanced gastric
      cancer were included. It was evaluated the quality of these included studies and
      analyzed data by Cochrane Collaboration's RevMan 5.0 software. RESULT: Ten RCTs
      were included meta analysis results suggested that compared with chemotherapy
      alone, the combination had a statistically significant benefit in healing
      efficacy (OR = 1.99, 95% CI: 1.26-3.13, P < 0.05) and improving quality of life
      (OR = 3.83, 95% CI: 2.38-6.15, P < 0.001). Besides, the combination also had a
      statistically significant benefit in myelosuppression, white blood cell (OR =
      0.44, 95% CI: 0.32-0.62, P < 0.001), hematoblast (OR = 0.40, 95% CI: 0.26-0.60, P
      < 0.001), liver function (OR = 0.33, 95% CI: 0.15-0.75, P < 0.05) and in reducing
      the gastroenteric reaction (OR = 0.32, 95% CI: 0.16-0.63, P = 0.001), decreasing
      the of CD3 ( MD = 2.96, 95% CI: 1.724. 20, P < 0.001), CD4 (MD = 9.04, 95% CI:
      7.87-10.20, P < 0.001), CD4/CD8 (MD = 0.47, 95% CI: 0.41-0.54, P < 0.001) and NK
      cells (MD = 5.90, 95% CI: 4.53-7.26, P < 0.001). CONCLUSION: Compared with
      cisplatin chemotherapy, compound matrine injection combined with cisplatin
      chemotherapy can significantly improve the efficiency, QOL and myelosuppression,
      and reduce adverse events.

PMID- 22375408
TI  - [Impact of Chinese herb on quality of life of stable chronic obstructive
      pulmonary disease: a randomized controlled study].
AB  - OBJECTIVE: To test and vertify the clinical efficacy of Chinese syndrome
      differentiation therapy in treating stable chronic obstructive pulmonary disease.
      METHOD: Two hundred and sixteen stable-COPD patients were randomly divided into 2
      groups: the treated group and control group, they were treated with respiratory
      exercises increases Chinese medicine and respiratory exercises increases placebo
      for 4 weeks respectively. Then evaluate the health-related quality of life of
      patients with stable COPD by using SF-36 before and after treatment. RESULT:
      Comparison of the health-related quality of life before and after treatment: the
      health-related quality of life in treated group was significantly improved after
      treatment and total score of SF-36 was better than control group (P < 0.05).
      CONCLUSION: Respiratory exercises increases Chinese medicine could improve the
      health-related quality of life significantly in patients with stable COPD,
      moreover its efficacy was superior to respiratory exercises increases placebo.

PMID- 22375409
TI  - [Clinical study of kangai injection plus FLAG regimen for refractory/relapsed
      acute leukemia].
AB  - OBJECTIVE: To assess the efficacy and toxicity of the kangai injection
      combination of fludarabine (Flud), cytosine arabinoside (Ara-C), and granulocyte
      colony-stimulating factor (G-CSF) (FLAG) in refractory/relapsed acute leukemia
      (AL) patients. METHOD: From 2004 to 2010 in our hospital, the 49 cases of
      refractory/relapsed acute luekemia were randomly divided into treatment group (28
      cases) and control group (21 cases). The control group were treated by kangai
      injection plus FLAG regimen, and the control group were treated by FLAG regimen.
      RESULT: The remission rate of treatment and total effective rate treatment group
      were 57.1% (16/28) and 71.4% (21/28), the control group were 52.3% (11/21) and
      61.9% (13/21), there were no significant differences in the two groups. Duration
      of neutrophils less than 0.5 x 10(9)/L in treatment group was (14 +/- 6) day,
      control group was (23 +/- 3) day, Duration of platelet less than 25 x 10(9)/L in
      treatment group was (17 +/- 6) day, control group was (31 +/- 2) day, treatment
      group of III-IV degree of infection was 6.9% (1/28) and control group was 23.8%
      (5/21) between the two groups were significantly different (P < 0.05). treatment
      group of III- IV degree of gastrointestinal; toxicity was 10.7% (3/28) and
      control group was 28. 5% (6/ 21). CONCLUSION: Kangai injection plus FLAG regimen
      could increase the remission rate, shorten the period of bone marrow suppression,
      significantly reduced the incidence and degree of infection, play a important
      role in attenuated efficiency.

PMID- 22375410
TI  - [New idea of treatment of heart failure with traditional Chinese medical].
AB  - To discuss the potential role of medicinal herbs, especially those with effect of
      strengthening Qi, in the treatment of chronic heart failure (CHF) via modulating
      myocardial substrate metabolism. The relationships among heart failure,
      myocardial energetic metabolism and herbal medicine were analyzed in detail
      through reviewing and summarizing the accumulating knowledge and recent findings
      on myocardial metabolism, heart failure and herbal medicine. Either energy lack
      or abnormal energetic metabolism is one of the main causes to the initiation and
      development of heart failure. Recent studies suggest that the cardiac function in
      the patients with CHF could be improved by inhibiting the energy production from
      metabolism of fatty acid and enhancing the energy production from glucose
      metabolism. The concept of Qi in Chinese medicine is very close to the energy in
      western medicine. The decoction of Chinese medicine containing herbal medicine
      with effect of strengthening Qi and the herbal medicine themselves and their
      components were evidenced to be effective in improvement of heart failure and
      regulation of both lipid and glucose metabolism; more importantly, all these
      herbal medicine contain the multi-sugar which can be metabolized into single unit
      of sugar which may be metabolized as a substrate by myocardium and potentially
      produce the cardioprotective effect. Therefore, we may find out a novel way to
      explain why the herbal medicine with effect of strengthening Qi can improve
      cardiac function in patients with CHF. In other words, regulating myocardial
      metabolism is one of the mechanisms underlying the cardioprotection produced by
      herbal medicine with effect of strengthening Qi in the treatment of heart
      failure.

PMID- 22375411
TI  - [Research progress of anticancer mechanism of glycyrrhetinic acid].
AB  - Glycyrrhetinic acid is a major active ingredient in licorice, a famous
      traditional Chinese medicine. Many studies on its anti-tumor activities and low
      toxicity to normal cells have attracted a great deal of attention. Reports
      indicated that glycyrrhetinic acid inhibited the growth of tumor cells through
      inducing apoptosis, differentiation and the block of cell cycle, suppressing
      tumor metastasis, reversing the multidrug resistance. Glycyrrhetinic acid also
      presented synergistic effects combined with chemotherapeutics and could inhibit
      the carcinogenesis induced by carcinogen. With further studies on mechanism of
      anticancer actions, glycyrrhetinic acid is being expected to have a good prospect
      of development and application for cancer therapy.

PMID- 22375412
TI  - [Advances in the study of p53 in response to DNA damage].
AB  - p53 (encoded by TP53) is undoubtedly one of the most extensively studied genes
      and proteins. It is a highly potent transcription factor which, under normal
      circumstances, is maintained at low level. Both genotoxic and non-genotoxic
      stresses can induce p53 stabilized leading to changes in the expression of p53
      responsive genes. The biological outcome inducing this pathway can be either
      growth arrest and apoptosis or senescence to maintain the integrity of the genome
      or to delete the damaged cells. The biochemical activity of p53 itself and the
      cellular environment govern the choice between these outcomes in a cell type- and
      stress-specific manner. So, p53 is a pivotal tumour suppressor and a mainstay of
      our body's natural anticancer defence. This review could provide some useful
      information for further study on the mechanisms of tumorigenesis and its
      progression, and also could contribute to the discovery of antitumor agents.

PMID- 22375413
TI  - [Advances in the study of Mycobacterium tuberculosis protein phosphatase and its
      inhibitors].
AB  - Reversible protein phosphorylation regulates multiple biochemical events.
      Mycobacterium tuberculosis phosphatases play important roles in regulating the
      pathogen physiology and interference of host signaling. They are also involved in
      the evasion of host immune response and blockage of the phagosome-lysosome
      fusion. Selective inhibition of phosphatase represents an ideal new avenue of
      anti-tuberculosis drug design. In this paper, we update the progresses about the
      regulation network of Mycobacterium tuberculosis phosphatases including MptpA,
      MptpB, MstP, SapM and their inhibitors. These serve as the basis for further
      antituberculosis drug target.

PMID- 22375414
TI  - [M cell in vitro model and its application in oral delivery of macromolecular
      drugs].
AB  - The oral administration of bioactive macromolecular drugs such as proteins,
      peptides and nucleic acids represents unprecedented challenges from the drug
      delivery point of view. One key consideration is how to overcome the
      gastrointestinal tract absorption barrier. Recent studies suggest that microfold
      cell (M cell), a kind of specialized antigen-sampling epithelial cell which is
      characterized by a high endocytic rate and low degradation ability, may play an
      important role in macromolecule oral absorption. The development of an in vitro M
      cell coculture system and its modified models greatly advanced the study of M
      cells and the development of oral delivery system for macromolecular drugs. The
      special structure, function and formation characteristics, and biomarkers of M
      cell are summarized in this review. The applications of in vitro M cell models in
      developing oral delivery system ofbioactive macromolecular drugs are discussed.

PMID- 22375415
TI  - [Current status of non-viral vectors for siRNA delivery].
AB  - RNA interference (RNAi) is a newly developed technology. It is the different
      levels of gene silencing induced by specific degradation of targeted genes in
      vivo, and both exogenous and endogenous double-stranded RNAs could induce the
      specific degradation. RNAi has been applied in tumor therapy, viral infection,
      hepatitis B and many other diseases. siRNA is the effector molecule which induces
      the RNAi in vivo. But naked siRNA is easily degradated by RNases in vivo, and the
      half-life is short. Meanwhile, the transfection efficiency of the naked siRNA is
      comparatively low. So the naked siRNA needs the help of vectors to penetrate the
      cell membrane and take action. Viral vectors have the potential immunogenicity
      and mutagenicity in gene therapy. Therefore, non-viral vectors are drawing more
      and more attention. The latest development of the non-viral vectors is summarized
      in this review.

PMID- 22375416
TI  - [Selection and anti-cancer effects of siRNAs targeting HMGA2 gene].
AB  - High mobility group A2 protein (HMGA2), an architectural factor, is highly
      expressed in various cancer types including lung cancers. It is a candidate
      target for cancer therapy. RNAi is an effective gene silencing method with low
      cost and less time-consuming. It is possible to exploit this technology in
      therapy. Here, 5 siRNAs targeting Hmga2 gene (HMGA2 siRNA1-5) were designed and
      synthesized. MTT assay, colony formation assay, transwell assay and flow
      cytometry were used to evaluate the effects of these siRNAs on lung cancer cell
      lines (NCI-H446 and A549). Results from cell proliferation, clone formation,
      migration and apoptosis showed that HMGA2 siRNA1, 3, 5 could affect these aspects
      for both lung cancer cell lines. Among the five siRNAs, HMGA2 siRNA5 showed the
      greatest inhibition effects. The inhibition effects of HMGA2 siRNA5 are sequence
      specific and are not due to the induction of interferon response. Taken together,
      siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene
      therapy.

PMID- 22375418
TI  - [Enhancing effect of deoxynivalenol-mediated GRP78 down-regulation on heavy chain
      secretion and bioactivity of two-chain FVIII gene co-transfected cells].
AB  - Although two chain transfering separately could be used to overcome the volume
      limitation of adeno-associated virus vectors (AAV) in coagulation factor VIII
      (FVIII) gene delivery, it leads to chain imbalance for inefficient heavy chain
      secretion. In this study we aimed to improve the efficacy of two chain strategy
      in FVIII gene delivery through the degradation of glucose-regulated protein 78
      (GRP78) known as a protein chaperone in endoplasmic reticulum (ER) by
      deoxynivalenol (DON) to decrease GRP78-bound FVIII heavy chain. By treating the
      two-chain gene transduced 293 cells with DON, the heavy chain (HC) secretion and
      FVIII bioactivity were observed. Data showed that 293 cells after three hours
      post-treatment with DON at a concentration of 500 ng mL(-1) resulted in obvious
      decrease the level of GRP78 but no effect on the cell proliferation. The HC
      secreted from DON-treated cells transfected with HC gene alone was 59 +/- 11 ng
      mL(-1), higher than that secreted by control cells (15 +/- 4 ng mL(-1)), and the
      HC secretion was further increasing to 146 +/- 34 ng mL(-1) in light chain (LC)
      gene co-transfected cells with an activity measured up to 0.66 +/- 0.15 U mL(-1),
      also greater than control cells (76 +/- 17 ng mL(-1) and 0.35 +/- 0.09 U mL(-1)).
      Taken together, these data suggest that DON-mediated GRP78 down-regulation could
      improve the efficacy of two-chain FVIII gene transfering by facilitating HC
      secretion, providing an experimental basis for in vivo dual-AAV application in
      FVIII gene delivery.

PMID- 22375417
TI  - [The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of
      cultured rat trigeminal ganglion].
AB  - The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating
      and preventing primary headache over thousands of years, but the exact
      pharmacological mechanism of the main bioactive ingredient gastrodin remains
      unclear. In present study, the effects of gastrodin on calcitonin gene-related
      peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2
      (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro
      organ culture to explore the underlying intracellular mechanism of gastrodin on
      primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive
      neurons count, positive area, mean optical density and integrated optical density
      by means of immunohistochemistry stain were compared at different concentrations
      of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24
      hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated
      significantly concentration-dependent reduction of CGRP-ir (+) expression and its
      action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40
      mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir
      (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1))
      similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol
      L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride,
      which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was
      examined by Western blotting after co-cultured with optimal concentration of
      gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The
      result indicated that gastrodin significantly reduced pERK1/2 protein actions
      similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling
      transduction pathway may be involved in gastrodin intracellular mechanism. This
      study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+)
      neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its
      actions similar to the effective concentration of sumatriptan succinate,
      flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular
      signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing
      CGRP up-regulation in rat TG after organ culture.

PMID- 22375419
TI  - [Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase
      antibody Fab' fragment and lidamycin on tumor invasion and metastasis].
AB  - This study is to investigate the tumor invasion and metastasis inhibition effects
      of the immunoconjugate composed of lidamycin and anti-type IV collagenase
      monoclonal antibody Fab' fragment. Boyden chamber assay was used to evaluate the
      influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was
      used to measure the change of invasion factor MMP-2 and MMP-9's secretion, and RT
      PCR was adopted to determine TIMP-1 mRNA expression level. The immunoconjugate
      inhibition of tumor in situ metastasis was also tested in nude mice. The Fab'-LDM
      conjugates had dose-dependent inhibition effect on HT-1080 cells' invasion. At
      the concentrations of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the invasion by
      (60 +/- 12) % and (79 +/- 11) % respectively. At the concentration of 5 and 10
      nmol L(-1), the Fab'-LDM inhibited the secretion of MMP-2 by (42 +/- 8) % and (54
      +/- 6) % and that of MMP-9 by (57 +/- 3) % and (87 +/- 1) %, respectively. RT-PCR
      indicated that conjugates increased the anti-invasion factor TIMP-1 level. The in
      vivo experiment showed that, compared with the control group, the tumor
      inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 +/- 13) %, (86 +/
      26) %, (74 +/- 22) % respectively. In conclusion, Fab'-LDM could inhibit the
      invasion and metastasis of tumor and it might be a new tumor biotherapy agent.

PMID- 22375420
TI  - [Synthesis of seven sinapine analogs and their effects on the tension of smooth
      muscle of intestines isolated from rabbit].
AB  - Seven sinapine analogs (6a-6g) were synthesized using cinnamon acid or benzoic
      acid and their derivatives as starting materials, which obtained from substituted
      benzaldehyde and malonate. The structures of target compounds were characterized
      by IR, 1H NMR and elemental analysis. The effects of compounds 6a-6g on the
      smooth muscle of intestine isolated from rabbit were studied, and the
      experimental results showed that compounds 6a, 6d and 6g had diastolic action,
      while 6f had contractile action.

PMID- 22375421
TI  - [Study on semi-synthetic transforming technology for the natural product of
      isocorydione].
AB  - Transforming technology for semi-synthesized isocorydione from the natural
      product ofisocorydine was studied. The factors affecting on the reaction yield
      were investigated. UV spectrophotometry was used to indicate the semi-synthesized
      yield of isocorydione. The optimum reaction conditions were determined as
      following: reacting for 12 h in the solution of sodium dihydrogen phosphate at pH
      10, the temperature was 25 degrees C and the ratio of isocorydine to Fremy's
      radical was 1 : 2. Under the optimum conditions, the yield could reach up to
      50.0%. The molecular structure of isocorydione was elucidated by X-ray single
      crystal diffraction analysis for the first time.

PMID- 22375422
TI  - [Quality control of recombinant oncolytic adenovirus/p53].
AB  - To establish a detection method of oncolytic adenovirus/p53 and standard of
      quality control, human telomerase reverse transcriptase (hTERT) promoter, CMV
      fusion promoter containing hypoxia reaction element (HRE) and p53 gene were
      identified by vector DNA restriction enzyme digestion and PCR analysis. The
      result conformed that all modified regions were in consistent with theoretical
      ones. Particle number was 2.0 x 10(11) mL(-1) determined by UV (A260). Infectious
      titer was 5.0 x 10(10) IU mL(-1) analyzed by TCID50. In vitro p53 gene expression
      in human lung cancer cell H1299 was determined by ELISA, and A450 ratio of
      nucleoprotein in virus infection group to control group was 5.2. Antitumor
      potency was evaluated by cytotoxicity assay using human lung cancer cell A549,
      and the MOI(IC50) of this gene therapy preparation was 1.0. The tumor cells
      targeted replication ability of recombinant virus was determined by TCID50 titer
      ratio of filial generation virus between human lung cancer cell A549 and human
      diploid epidermal fibrolast BJ cells after infected by virus with same MOI.
      TCID50 titer ratio of tumor cell infection group to normal cell infection control
      group was 398. The IE-HPLC purity of virus was 99.5%. There was less than 1 copy
      of wild type adenovirus within 1 x 10(7) VP recombinant virus. Other quality
      control items were complied with corresponding requirements in the guidance for
      human somatic cell therapy and gene therapy and Chinese pharmacopeia volume III.
      The detection method of oncolytic adenovirus/p53 was successfully established for
      quality control standard. The study also provided reference for quality control
      of other oncolytic viral vector products.

PMID- 22375423
TI  - [Identification of metabolites of nobiletin in rats using ultra-performance
      liquid chromatography coupled with triple-quadrupole mass spectrometry].
AB  - In this study, metabolism of nobiletin in rats was studied using ultra
      performance liquid chromatography coupled with tandem mass spectrometry (UPLC
      MS/MS). As a result, seven major metabolites were found in bile, urine and serum
      of rats. Three phase I products were assigned to be demethyl and di-demethyl
      products, and other four phase II products were assigned to be glucuronic and
      sulfonic conjugates. The four phase II metabolites were reported for the first
      time. Among the metabolites found in the present study, the glucuronic conjugates
      of demethyl-nobiletin played a predominant role in the metabolic pathway,
      indicating that its potential role for glucuronidation-related factors, such as
      gene polymorphism, drug-drug interaction, etc., in changing the active and toxic
      effect of nobiletin and that it should be paid more attention in further
      development.

PMID- 22375424
TI  - [UPLC-TOF/MS based chemical profiling approach to evaluate toxicity-attenuated
      chemical composition in combination of ginseng and radix aconiti praeparata].
AB  - In the present study, an ultra performance liquid chromatography coupled with
      time-of-fight mass spectrometry (UPLC-TOF/MS) based chemical profiling approach
      was used to evaluate chemical constitution between co-decoction and mixed
      decoction of ginseng and Radix Aconiti Praeparata. Two different kinds of
      decoctions, namely co-decoction of ginseng and Radix Aconiti Praeparata: water
      extract of mixed two herbs, and mixed decoction of ginseng and Radix Aconiti
      Praeparata: mixed water extract of each individual herbs, were prepared. Batches
      of these two kinds of decoction samples were subjected to UPLC-TOF/MS analysis.
      The datasets of t(R) m/z pairs, ion intensities and sample codes were processed
      with supervised partial least squared discriminant analysis (OPLS-DA) to
      holistically compare the difference between these two decoction samples.
      Significant difference between the two decoction samples was showed in the
      results of positive ion mode. The contents of hypaconitine and deoxyaconitine
      decreased, while that of benzoylmesaconine, benzoylhypaconine and dehydrated
      benzoylmesaconine increased in the samples of co-decoction of ginseng and Radix
      Aconiti Praeparata. The content of diester-diterpenoid alkaloids decreased, while
      that of monoester-diterpenoid alkaloids increased, which is probably the basis of
      toxicity-attenuated action when combined ginseng with Radix Aconiti Praeparata.

PMID- 22375425
TI  - [Estimation of individual pharmacokinetic parameters using maximum a posteriori
      Bayesian method with D-optimal sampling strategy].
AB  - This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation
      method to estimate individual pharmacokinetic parameters based on D-optimal
      sampling strategy. Meanwhile, the performance of MAPB was compared with the
      multiple linear regression (MLR) method in terms of accuracy and precision.
      Pharmacokinetic study of pioglitazone was employed as the example case. The
      population pharmacokinetics was characterized by nonlinear mixed effects model
      (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal
      algorithm using WinPOPT software. The simulated data generated by Monte Carlo
      method were used to access the performance of MAPB and MLR. As the number of
      samples per subject decreased, the accuracy and precision of MAPB method tended
      to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design
      had less bias with low inter-individual variability, and had more bias and
      imprecision with high residue variability. The estimation of AUC by MAPB using D
      optimal 2 points design had similar accuracy and precision to MLR. However, MAPB
      estimation was better than MLR while adjusting the sampling time to one hour.
      Overall, the MAPB method had similar predictive performance as MLR, but MAPB
      could provide more pharmacokinetic information with higher sampling flexibility.

PMID- 22375426
TI  - [Simultaneous determination of 11 opiates in hair by liquid chromatography-tandem
      mass spectrometry].
AB  - The paper reports the establishment of a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples,
      and the study of presence of opiates in the hair of active heroin addicts. About
      20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer
      solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as
      internal standards, and then extracted with the mixture of dichlormethane and
      isopropanol, separated by the Allure PFP propyl column with a mobile phase
      consisting of acetonitrile and 20 mmol L(-1) ammonium acetate buffer, and then
      analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze
      11 opiates. Eleven opiates showed a fairly good linearity over the corresponding
      range (r > 0.996 0). The detection limits were less than 0.05 ng mg(-1). The
      recoveries were between 47.2% and 110%, and the deviations of intra- and inter
      day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine,
      acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts.
      The developed method shows high sensitivity and selectivity, and is suitable for
      the simultaneous analysis of 11 opiates in hair samples and identify legal and
      illegal use of opiates.

PMID- 22375427
TI  - [Optimization of a floating osmotic pump system of ambroxol hydrochloride using
      central composite design-response surface methodology and its pharmacokinetics in
      Beagle dogs].
AB  - This paper reported that a new type of floating osmotic pump of ambroxol
      hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010,
      appendix XD) was employed to simultaneously evaluate the release and floating
      behavior in vitro. The system was optimized using central composite design
      response surface methodology. Similar factor (f2) between the release profile of
      self-made formulation and the target release profile was chosen as dependent
      factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating
      (C, %) were employed as independent factors. Optimized formulation was: A (100.99
      mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market
      capsules (69.02) and self-made tablets (72.15). It was showed that self-made
      capsules possessed character of zero-order release (r = 0.994 4) and drug release
      completely (>90%). It was showed in result of in vivo study that tmax and Cmax of
      self-made capsules were significantly lower than that of market capsules and self
      made tablets. The correlation coefficient between the fraction of absorption in
      vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of
      self-made capsules was 110.77%. Accordingly, self-made capsules displayed
      obviously characteristics of controlled release both in vivo and in vitro.

PMID- 22375428
TI  - [Characterization of vinflunine tartrate liposomes in vitro and in vivo].
AB  - Vinflunine tartrate-loaded liposomes (VT-L) with two drug-to-lipid ratios were
      prepared by pH gradient method. Vesicle size and zeta potential were determined
      by the Zetasizer Nano ZS. Entrapment efficiency was evaluated by cation exchange
      resin centrifugalization method. The toxicity and tumor inhibition to nude mouse
      administrated by VT-L with different drug-to-lipid ratios were investigated and
      compared with the vinflunine tartrate injection (VT-I). The results showed that
      the mean particle size, zeta potential and entrapment efficiency of the VT-L with
      drug-to-lipid ratios of 1 : 5 and 1 : 10 were 124.6 nm and 128.3 nm, -25.3 mV and
      -22.8 mV, 94.46% and 97.31%, respectively. The VT-L with two different drug-to
      lipid ratios has significantly higher anti-tumor effect to nude mouse
      transplanted human non-small cell lung carcinoma A549 and lower toxicity than VT
      I. While there were no significant differences in anti-tumor effect and toxicity
      between VT-L with two different drug-to-lipid ratios.

PMID- 22375429
TI  - [Preparation and evaluation of enteric-coated and taste masking clarithromycin
      granules].
AB  - The study is to prepare taste masking and enteric-coated clarithromycin granules
      by melting and fluid bed coating technology. Clarithromycin and matrix materials
      were melted at a certain temperature, and then made into particles by fluidized
      bed coating. X-ray powder diffraction and scanning electron microscopy were used
      to identify the crystal and morphology of drug loading granules. In vitro
      dissolution method was used for the observation of the drug release behavior. The
      results showed that the drug particles size range was 0.2 - 0.6 mm; the crystal
      form of clarithromycin in the granule did not change; enteric-coated granules
      accumulated release in 0.1 mol L(-1) hydrochloric acid in 2 h was less than 10%,
      while in pH 6.8 phosphate buffer in 1 h was more than 80%. The taste masking and
      enteric-coated clarithromycin granules not only have good taste masking effect,
      but also have a good release behavior. It is expected to have better clinical
      application.

PMID- 22375431
TI  - Aging patients deserve respect, empathy and quality of life.

PMID- 22375430
TI  - [In vitro study on gastrointestinal absorption of FITC labeled pilose antler
      protein extraction].
AB  - An in vitro detection method of the gastrointestinal absorption of Pilose Antler
      protein was established for mixed protein activity. Five bands of protein with
      molecular weight of 17.8-160 kD derived from the Pilose Antler were extracted and
      sufficiently labeled with FITC (FITC-PE). The stability and variation of FITC-PE
      in gastrointestinal circumstances were detected by native polyacrylamide gel
      electrophoresis and confocal laser scanning microscope. Results showed that the
      main component of FITC-PE kept invariant after being reacted with artificial
      gastric fluid and artificial intestinal fluid. The fluorescence signal was
      detected 20 min after administration in the valgus intestinal purse experiment,
      and three kinds of protein, with molecular weight of 45, 25, and 17.8 kD, were
      detected in the mixture of absorbent protein. The research laid the foundation
      for the further in vivo study of Pilose Antler protein. Meanwhile, it would be an
      in vitro screening method for the absorption, distribution and metabolism of
      mixed protein from traditional Chinese medicine.

PMID- 22375432
TI  - I do not buy green tomatoes.

PMID- 22375433
TI  - Consult the muse for solutions to primary care crisis?

PMID- 22375434
TI  - Do new pain clinic laws affect my prescribing of pain meds?

PMID- 22375435
TI  - Insurance experts: an unsung benefit of TMA membership.

PMID- 22375436
TI  - Geriatrics: the fractionated field theory--less is the new more!

PMID- 22375437
TI  - Dementia: a patient's most frequently-asked questions.

PMID- 22375438
TI  - Elder Justice Act (EJA): comparing new elder abuse laws to Tennessee law.

PMID- 22375439
TI  - Subungual melanoma: diagnosis and management.
AB  - Subungual Melanoma accounts for less than three percent of all cutaneous
      melanomas and has a dismal prognosis. Our case report outlines the current
      approach for diagnosis and management of this rare form of acral lentiginous
      melanoma.

PMID- 22375440
TI  - Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy.
AB  - A 36-year-old female developed bone marrow failure diagnosed as myelodysplastic
      syndrome (MDS) (Sidebar), followed shortly by a peripheral neuropathy and a gait
      disturbance. While waiting for a bone marrow transplant, she reported to us that
      she had seen attorney-generated, televised advertisements concerning the role of
      denture adhesives relating to her malady. Labs were then obtained demonstrating
      she had dramatic and unsuspected hypocupremia and hyperzincemia. Administration
      of copper and cessation of denture adhesives resulted in recovery of her
      hematopoietic system and partial resolution of the neurological sequela.

PMID- 22375441
TI  - Interesting EKG: all that looks saw-toothed is not flutter.

PMID- 22375442
TI  - Fluconazole mouthrinse and clotrimazole mouthpaint effective medications for
      patients with denture stomatitis (UT CAT #802).

PMID- 22375443
TI  - Reaching the Texas dental goals of healthy people 2010.
AB  - BACKGROUND: The U.S. Department of Health and Human Services has promoted Healthy
      People 2010, which is a set of national health objectives for the nation to
      achieve over the first decade of the new century (1). Texas has not yet met its
      target of 50 percent of 8-year-old children with dental sealants having been
      placed on their 6-year molars, which is one of the Healthy People 2010 goals. An
      assessment of the dental needs of children in Tarrant County, Texas, was
      initiated by the JPS Health Network (named after John Peter Smith). The JPS
      Health Network established the Healthy Smiles program to address the dental needs
      of the students in this county because a school based dental sealant program
      would be effective in reducing dental decay. METHODS: Approved Title One
      elementary schools in Tarrant County were scheduled for dental screenings,
      education, and fluoride and dental sealant applications. Students were given
      visual dental screenings and classified as to future dental needs. First grade
      students received fluoride varnish and second and third grade students received
      fluoride and dental sealants. RESULTS: For the 2010-2011 school year: A total of
      28,322 students were seen by dental professionals from the JPS Health Network;
      8,348 dental sealants were placed; and 11,825 fluoride applications were given by
      dental staff. CONCLUSIONS: The JPS Health Network Healthy Smiles Program proved
      to be an effective way to deliver oral preventive care and dental education to a
      large number of low-income students. CLINICAL IMPLICATIONS: Dental caries
      prevention programs such as Healthy Smiles could help Texas reach its goals for
      improved oral health for the children of Texas.

PMID- 22375444
TI  - Shear bond strengths of a selenium containing and a conventional light cured
      adhesive for orthodontic bonding.
AB  - BACKGROUND: The objectives of this study were to evaluate the debonding strength
      and mode of failure of a selenium containing adhesive compared to an established
      orthodontic adhesive. MATERIALS AND METHODS: One hundred sixty bovine mandibular
      incisors were allocated to eight groups: steel and clear brackets were bonded
      with either selenium containing adhesive (Group 1: SeLect Defense) or a
      conventional light-cured adhesive (Group 2:Transbond XT) to measure debond
      strength and the adhesive remnant index was used to assess the location of bond
      failure. Data was evaluated using a three-way analysis of variance and Fisher's
      PLSD multiple comparisons test for mean debond strengths. RESULTS: Group 2 debond
      strengths were greater than that of Group 1 with the steel and clear brackets.
      Group 1 debond strengths were greater with clear than with steel brackets at both
      time points. Both adhesives demonstrated increased debond strengths from zero to
      24 hours and the clear brackets exhibited a greater ARI than steel after
      debonding. Comparisons of debond strength means among adhesives, brackets, and
      times were all statistically significant. CONCLUSIONS/DISCUSSION: All debond
      strengths were within a clinically acceptable range according to previous
      literature. SeLect Defense may be desirable due to its potential for preventing
      white spot lesions despite the reduced strength compared to Transbond XT.

PMID- 22375445
TI  - Oral health and social justice: opportunities for leadership.

PMID- 22375446
TI  - Sumter S. Arnim, D.D.S., Ph.D.: Texas leader in evidence-based dentistry.
AB  - Many lessons can be learned from the career of Dr. Sumter Arnim, chief among them
      that we have a professional obligation to apply scientific knowledge to the
      practice of dentistry and to involve our patients in their dental care, and to
      share this translational knowledge with one's colleagues. Arnim's work was an
      honor not only for the University of Texas Dental Branch (now, The University of
      Texas School of Dentistry at Houston), but for every school and student with whom
      he interacted. Our profession is better for having had Sumter Arnim as one of its
      members, and he can be credited with having played a leadership role in what is
      now known as evidence-based dentistry in Texas, the United States, and beyond.
      One of the authors of this paper (JVJ) had the opportunity to be a student at the
      University of Texas Dental Branch during the time that Dr. Sumter Arnim was
      faculty member. Dr. Arnim was deservedly respected by his students and faculty
      colleagues alike, due in no small part to his dedication to dentistry. This
      dedication to the profession was well known, as Dr. Arnim had been accepted to
      Yale University Medical School, but soon after enrollment there, he elected to
      pursue a Ph.D. degree in Pathology, rather than M.D. Dr. Arnim constantly
      stressed the bacteriologic nature of dental disease and the value of prevention
      to his Dental Branch students, serving as Director of the Postgraduate School
      with great distinction. His steadfast belief in the biological basis of dentistry
      was manifest in his frequent admonition to the student body: "You can either be
      doctors or hardware merchants." Finally, it is ironic that in 2011, the American
      Dental Association has reiterated some of Arnim's career themes in its current
      publication on barriers to oral health in the United States, with primary
      messages that include, "Prevention is essential. A public health model based on
      the surgical intervention in disease that could have been prevented after that
      disease has occurred, is a poor model," and, "Treating the disease without
      educating the patient is a wasted opportunity."

PMID- 22375447
TI  - Oral and maxillofacial pathology. Case of the month. Antral pseudocyst.

PMID- 22375448
TI  - Planning for esthetics--part 1: single tooth bone level implant restorations.

PMID- 22375449
TI  - Should I get an AED for my office? If so, what do I need to know?

PMID- 22375450
TI  - Surgery is front and center in new Medicare value-based purchasing.

PMID- 22375451
TI  - Study: uptick in younger RNs boosts workforce.

PMID- 22375452
TI  - Data for benchmarking your OR's performance.

PMID- 22375453
TI  - 'Operation zero' targets surgical site infections.

PMID- 22375454
TI  - Hospitals losing on physician preference items.

PMID- 22375455
TI  - Taking control of implant processing practices.

PMID- 22375456
TI  - Providing safe care for obese patients in the ASC.

PMID- 22375457
TI  - What's expected for use of safe surgery checklist?

PMID- 22375458
TI  - Natural language processing improves coding accuracy.

PMID- 22375459
TI  - 'Home' work: becoming a PCMH.

PMID- 22375460
TI  - ACO invitations: a date worth debating.

PMID- 22375461
TI  - A social approach to marketing.

PMID- 22375462
TI  - Measure meaningful use.

PMID- 22375464
TI  - What it takes to become a PCMH.

PMID- 22375463
TI  - Game changer: a new approach to strategic planning.

PMID- 22375465
TI  - Concierge medicine: glitz and glamour or good medicine?

PMID- 22375466
TI  - Who controls remote (coding) in your practice?

PMID- 22375467
TI  - Future shock: are you ready for new payment methods?

PMID- 22375468
TI  - PCMH, ACO measures help prepare groups for value-based care.

PMID- 22375469
TI  - Maximize practice income.

PMID- 22375470
TI  - Mind the gap!

PMID- 22375471
TI  - When disaster strikes, will your practice be lucky or lost?

PMID- 22375472
TI  - How social do you want to be?

PMID- 22375473
TI  - Health reform demands collaboration.

PMID- 22375474
TI  - Know your risks, help mitigate them.
AB  - With multimillion dollar penalties threatening health organizations, risk
      management policies are scaling the list of daily priorities.

PMID- 22375475
TI  - Are you ready for audits.
AB  - Audits can cost your practice thousands--if not millions--of dollars. Protect
      yourself with internal audits to ensure compliance.

PMID- 22375476
TI  - Field guide: seeing the trees through the forest in 2012.

PMID- 22375477
TI  - Unintended consequences: identifying and mitigating unanticipated issues in EHR
      use.

PMID- 22375478
TI  - Rounding with scribes: employing scribes in a pediatric inpatient setting.
AB  - Using scribes to document patient encounters for physicians offers both benefits
      and challenges. A pediatric hospital recounts its experience adding scribes to
      its inpatient rounding teams.

PMID- 22375479
TI  - Breathing room: early adopters have more time for stage 2.

PMID- 22375480
TI  - Understanding different healthcare legal documents.

PMID- 22375481
TI  - Metadata for HIM: ISO standards for global interoperability.

PMID- 22375482
TI  - Creating a legal health record definition.

PMID- 22375483
TI  - Managing a data dictionary.

PMID- 22375484
TI  - The respiratory system and ICD-10-CM/PCS.

PMID- 22375485
TI  - ICD-9-CM diagnostic coding for shiga toxin-producing Escherichia coli.

PMID- 22375486
TI  - Expecting a bargain: HIM directors at risk of underestimating ICD-10 coder
      training costs.

PMID- 22375487
TI  - Clinical evaluation of the safety and immunogenicity of H5N1 pandemic influenza
      vaccines.

PMID- 22375488
TI  - [Role of immune alterations induced by papillomavirus in development of cervical
      cancer ].
AB  - Squamous cell cancer of the uterine cervix is associated with a high morbidity
      and mortality worldwide and in Belgium. The link between cervical cancer and HPV
      has generated, in recent years, a great interest for studies aiming to better
      understand the role of the immune system in the control of these infections and
      for the development of prophylactic anti-HPV vaccines. The purpose of this work
      was to analyse the immune co-factors implicated in the promotion of the
      neoplastic process. We have shown that both virus-induced immune alterations and
      squamous metaplasia in the transformation zone of the uterine cervix play a role
      to create an immunotolerogenic microenvironment during the cervical
      carcinogenesis.

PMID- 22375489
TI  - [Allogeneic hematopoietic stem cell treatment after non-myeloablation
      (minigraft)].
AB  - Allogeneic haematopoietic stem cell transplantation is the best treatment option
      for many patients suffering from severe haematologic diseases. Allogeneic
      transplantation is generally preceded, by a myeloablative conditioning regimen
      consisting of high doses of chemo/radiotherapy. The use of those high dose
      conditionings is restricted to young patients (< 55 years of age) without
      significant comorbidities. Unfortunately, median patient age at diagnosis of most
      haematological malignancies ranges from 60 to 70 years. It has been accepted
      since the late 1970s that the occurrence of acute and/or chronic graft-versus
      host disease (a life-threatening complication of allogeneic transplantation
      consisting of host organ destruction by donor T cells present in the graft) leads
      to a dramatic decreased risk of relapse thanks to the destruction of host tumour
      cells by donor T cells (graft-versus-tumour effects). These observations led
      several groups of investigators to develop non-myeloablative conditionings for
      allogeneic haematopoietic stem cell transplantation (also termed mini-transplant)
      based nearly exclusively on graft-versus-tumour effects for tumour eradication.
      After a brief introduction, this article reviews preliminary results of
      nonmyeloablative transplantation and then present some perspectives aimed at
      increasing the efficacy while decreasing the toxicity of this approach.

PMID- 22375490
TI  - [Should medicine encourage doing? Biomedical engineering ideals and the issue of
      improving humans].
AB  - In the contemporary biomedicine, the new medicines and technologies can be used
      not only to cure the patients but also to enhance human capacities: genetic
      design, alteration of cognitive and emotional functions, increase in life-span,
      or to boost performances in sport... This evolution represents a paradigmatic
      change in the medical practice. It is not the mere restoration of health which is
      expected anymore. What is required is "the perfectibility of the human being". In
      this article, the emergence of the "enhancement technologies" is examined from an
      ethical and philosophical perspective.

PMID- 22375491
TI  - [In search of the musical brain].
AB  - The emotional power of music opens novel prospects in the field of affective
      neurosciences. To clarify the neurobiological substrate of emotions brought by
      music, we adopted an integrative approach, which combines neuropsychology, brain
      imaging and electrophysiology (intracranial depth electrode recordings). The
      results of a series of studies carried out in patients with focal brain lesions
      allow to describe the involvement of different temporal lobe regions and, in
      particular, of the amygdala in these emotional judgments before discussing the
      therapeutic benefits of music to handle Alzheimer's disease.

PMID- 22375492
TI  - [Music, composers and psychopathology: the psychiatrist's view].
AB  - A first reason for the psychiatrist to be interested in music, musicians and
      their artistic work, comes from the strong biographical and scientific evidence
      linking mood disorders and in particular, bipolar disorder, to artistic
      creativity. Moreover, a family association between psychopathology and creativity
      has been found in several studies. Important changes in mood, but also cognition,
      personality and behaviour can occur during all phases of manic-depressive illness
      and these changes have potentially important effects on creativity and
      productivity. Those changes are usually opposite in mania and depression. Many
      bipolar artists see emotional turmoil as essential to their creativity, which has
      therapeutical but also ethical consequences. A second area of interest is the
      impaired emotional recognition in schizophrenic patients, not only for visual
      material (faces or contextual scenes) but also for auditive material (voice or
      music) leading to impaired social interactions in this condition.

PMID- 22375493
TI  - [Contributions of immunogenic cell death to the efficacy of anticancer
      chemotherapy].
AB  - Immunogenic cell death, characterized by calreticulin exposure on the surface of
      the dying cell, release of the nuclear protein high mobility group box 1 (HMGB1),
      and release of ATP, enables stimulation of the immune system. We outlined the
      importance of this kind of cell death for the success of some anticancer
      chemotherapies. However, defects in the immunogenic cell death signalling pathway
      can lead to therapeutic failure, apparently because anticancer immune responses
      must contribute to the efficacy of chemotherapeutic regimens. These defects can
      be related to the therapy, the tumour cell, the host or the tumour-host
      interface. It is necessary to characterize these defects to restore and improve
      the efficacy of anticancer chemotherapies.

PMID- 22375494
TI  - [Cancer stem cells].
AB  - In tumours, a significant fraction of neoplastic cells are engaged in the cell
      cycle (growth fraction) and are therefore targets for radiation therapy and
      chemotherapy. Unfortunately, in most disseminated cancers, such treatments cannot
      lead to complete cure. Many different mechanisms have been described to explain
      this resistance. The hypothesis of the existence of "cancer stem cells "has been
      recently proposed. Indeed, the tumour would contain a small subpopulation of
      cancer cells displaying the phenotypical characteristics of multipotential stem
      cells. Since such cells display different signalling pathways compared with more
      differentiated cells, this might explain at least partially the resistance to
      treatments. Chronic myeloid leukaemia is a good model in favour of cancer stem
      cells, but the presence of such cells in all types of cancers is still a matter
      of debate. Several questions emerge: is the multipotential stem cell, the cell of
      origin of cancer? What is the relevance of the cancer stem cell paradigm for
      understanding cancer cell biology and to envision new therapeutic, hopefully
      curative, therapies? The case of chronic myeloid leukaemia is used to discuss
      these questions.

PMID- 22375495
TI  - [Surgical treatment of female stress urinary incontinence: where are we in
      2011?].
AB  - Female stress urinary incontinence (SUI) is mainly due to an excessive mobility
      of the cervico-urethral complex. Synthetic tapes placed without tension
      underneath the urethra to correct this hypermobility have revolutionized the
      surgical treatment of female SUI for the past fifteen years. The retropubic
      approach, namely the "tension-free vaginal tape" (TVT), was designed in 1996. It
      generates high SUI cure rates but is associated with a risk of intrapelvic
      bleeding and bladder and intestine perforation. The inside-out transobturator
      approach, which was developed eight years ago in our Institution, has since been
      used worldwide. The surgical technique is simple and reproducible and the
      incidence of peri- and post-operative complications is reduced. SUI cure rates
      are +/- 90% after a 3-5 years follow-up, similar to those obtained after the
      retropubic route. We have recently improved our original technique by using a
      shorter tape while, at the same time, minimizing the dissection required for its
      insertion. After a one year minimum follow-up, this new technique appears as safe
      and efficient as the traditional transobturator technique but is associated with
      reduced post-operative groin pain. We introduce for the first time the concept of
      the transobturator "midi sling".

PMID- 22375496
TI  - [Utilization of screening and treatment of prostate cancer in 2011].
AB  - Prostate cancer is the most prevalent cancer in men aged fifty or more. Resulting
      mortality, however, is low since most prostatic cancers are slow-growing, non
      lethal tumours. The introduction of PSA screening has profoundly impacted on the
      epidemiology of prostate cancer. Men bearing aggressive disease are diagnosed
      sooner so that radical treatment can be applied more effectively. But PSA
      screening also unveil many indolent cancers that would have not threaten the
      patient if left undiscovered. Systematic treatment of indolent cancers may result
      into many men being exposed to unwanted side effects. For this reason, the true
      benefit of PSA screening is still a matter of intense debate. Nevertheless, there
      is room for an ethical approach of prostate cancer screening, based on
      information, correct identification of aggressive disease and early integration
      of new biomarkers.

PMID- 22375497
TI  - [Do as Norway, differ between acute and elective].

PMID- 22375498
TI  - [Are there any nice physicians here? The ginger cookie's nice-effect now
      researched--cross-over study shows no connection].

PMID- 22375499
TI  - [High-fat diet not harmless--serious health risks have been surveyed.
      Atherosclerosis, breast and colonic cancer, depression, reduced memory,
      dependence...].

PMID- 22375500
TI  - [Health literacy basic in meeting with the patients. It comprises skills to make
      independent decisions in health care].

PMID- 22375501
TI  - [Fatal disseminated nocardiosis. However the prognosis is good in early diagnosis
      and treatment].

PMID- 22375502
TI  - [Polycystic ovarian syndrome].

PMID- 22375503
TI  - [The dangerous silence].

PMID- 22375504
TI  - [The mummy in Falun--memory from doctor Prag's royal journey].

PMID- 22375505
TI  - What do our patients think personalized medicine means? The answer may surprise
      you.

PMID- 22375506
TI  - Genetic profiling for personalized cancer care.

PMID- 22375507
TI  - How has genetic testing changed treatment approaches for patients with lung
      cancer?

PMID- 22375508
TI  - Nursing considerations for patients receiving pazopanib for renal cell carcinoma.

PMID- 22375509
TI  - The case of the harmful herbs.

PMID- 22375511
TI  - The fine line between patient rights and biospecimen research.

PMID- 22375510
TI  - Cancer therapies are linked to thyroid dysfunction.

PMID- 22375512
TI  - Role of entropy and autosolvation in dimerization and complexation of C60 by Zn7
      metallocavitands.
AB  - The supramolecular chemistry of bowl-shaped heptazinc metallocavitands templated
      by Schiff base macrocycles has been investigated. Dimerization thermodynamics
      were probed by (1)H NMR spectroscopy in benzene-d(6), toluene-d(8), and p-xylene
      d(10) and revealed the process to be entropy-driven and enthalpy-opposed in each
      solvent. Trends in the experimentally determined enthalpy and entropy values are
      related to the thermodynamics of solvent autosolvation, solvent molecules being
      released from the monomeric metallocavitand cavity into the bulk solvent upon
      dimerization. The relationship established between experimentally measured
      dimerization thermodynamics and autosolvation data successfully predicts the
      absence of dimerization in CH(2)Cl(2) and CHCl(3) and was used to estimate the
      number of solvent molecules interacting with the monomeric metallocavitand in
      solution. Host-guest interactions between heptazinc metallocavitands and
      fullerene C(60) have also been investigated. Interestingly, metallocavitand-C(60)
      interactions are only observed in solvents that facilitate entropy-driven
      dimerization suggesting entropy and solvent autosolvation may be important in
      explaining concave-convex interactions.

PMID- 22375513
TI  - New CDC campaign to increase HIV testing.

PMID- 22375514
TI  - alpha(+)-Thalassemia trait caused by a frameshift mutation in exon 2 of the
      alpha2-globin gene [HBA2 c.244delT].
AB  - We report a case of alpha(+)-thalassemia (alpha(+)-thal) trait caused by a novel
      frameshift mutation in exon 2 of the alpha2-globin gene, specifically a deletion
      of a single nucleotide at amino acid codon 81 [HBA2 c.244delT]. The mutation
      results in a premature termination of translation at codon 83.

PMID- 22375515
TI  - Cystic lesions of the pancreas: more reliable differentiation with in situ high
      resolution optical imaging?

PMID- 22375516
TI  - Role of intracellular acid Ca(2+) stores in pathological pancreatic protease
      activation.

PMID- 22375517
TI  - Targeting opioidergic pathways as a novel biological treatment for advanced
      pancreatic cancer.

PMID- 22375519
TI  - First WGO regional meeting with the TSG: a template for future regional
      gastroenterology collaborations.
AB  - The World Gastroenterology Organization that, for decades, has organized a
      quadrennial world congress of gastroenterology in various parts of the world,
      recently collaborated, in conjunction with the Turkish Society of
      Gastroenterology, in its first regional meeting in Antalya, Turkey. This venture
      was embarked upon for several reasons: first, to collaborate with a major
      national gastroenterology organization; second, to address regional issues in
      digestive diseases; and third, to provide an accessible forum for education in
      the science and practice of gastroenterology to individuals from areas (e.g.,
      Central Asia) where the specialty remains relatively under-developed. The success
      of the endeavor can be gauged, not only by an attendance of over 1000
      individuals, but also by the level of interaction that took place between
      colleagues from Europe and North America, on the one hand, and Turkey and
      surrounding regions and the rest of the world, on the other. The emphasis was
      firmly on issues that are relevant to the area and on the development of
      education and training in gastroenterology in the region: approaches that must,
      ultimately, impact positively on the care of those afflicted by digestive
      disorders in these nations.

PMID- 22375520
TI  - Evaluating slow-transit constipation in patients using laxatives: a better
      approach or do we need improved patient selection?
AB  - Slow-transit constipation is a relatively frequent subtype of constipation, often
      refractory to medical treatment. Clinical information is usually obtained in
      patients during laxative withdrawal; thus, data on the effect of laxatives on
      their daily symptoms are lacking. The evaluated article reports on the effects of
      laxatives on symptoms (stool frequency, stool form, straining at stool, pain and
      bloating) and on laxative use by means of a daily stool questionnaire. Most
      patients used laxatives on an intermittent basis, and a minority also used
      associated enemas. Use of laxatives yielded an almost average normal daily number
      of evacuations in this group, with only a minority having less than three bowel
      movements per week. The days in which patients used laxatives yielded
      significantly more frequent and loose stools compared with those without
      laxatives. Thus, the use of laxatives seems to influence the clinical aspects of
      patients with slow-transit constipation, and this should be considered when
      evaluating these participants.

PMID- 22375521
TI  - Radiotherapy in the adjuvant management of pancreatic adenocarcinoma: is it
      helpful?
AB  - Curative-intent management for pancreatic adenocarcinoma requires gross total
      resection. Only 15-20% of patients are eligible for resection and of these only
      approximately 20% are long-term survivors. Adjuvant and neoadjuvant approaches
      have been, and are being, sought to improve upon surgical results. Radiotherapy
      has a role in the adjuvant management of many gastrointestinal malignancies and
      historically has also had a role in the adjuvant management of pancreatic
      adenocarcinoma. However, the role of radiotherapy in the management of pancreatic
      adenocarcinoma has been called into question. This review examines this
      controversy and the underlying issues and considers current efforts towards
      resolving them, as well as some likely future developments.

PMID- 22375522
TI  - Nonalcoholic fatty liver disease and bariatric surgery.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of
      chronic liver disease worldwide. Treatment recommendations for NAFLD are aimed
      towards weight reduction, thereby reducing insulin resistance. Unfortunately,
      lifestyle modifications have not yielded long-term success, while durable weight
      loss is routinely achieved with bariatric surgery. This article reviews the
      effects of bariatric surgery on patients with NAFLD. In these patients,
      postsurgical evaluations of liver histology by repeat liver biopsy are hindered
      by the risk of the procedure and the inherent sample variability, which makes the
      impact of bariatric surgery on NAFLD difficult to quantify. In longitudinal
      studies of NAFLD, the biopsy-based evaluations should be augmented by repeated
      measurements of the noninvasive biomarkers that may provide an insight into the
      changes in the physiological state of the liver after bariatric or other types of
      interventions. Nevertheless, currently available tests are not able to provide
      this type of in-depth outcome measures for these patients.

PMID- 22375523
TI  - Role of the multidisciplinary team in the diagnosis and treatment of
      hepatocellular carcinoma.
AB  - It has long been appreciated that hepatocellular carcinoma (HCC) is a complex
      disease. HCC is typically preceded by liver cirrhosis, which is itself caused by
      various types of hepatitis of both viral and nonviral etiologies. Thus, the
      treatment of patients with HCC requires multiple healthcare professionals,
      including hepatologists, medical oncologists, surgical oncologists,
      transplantation surgeons, diagnostic radiologists, pathologists, nurses, nurse
      practitioners and interventional radiologists. These specialists should meet
      regularly to review patients' progress, ensure that treatments are individualized
      for each patient and agree on next steps. We review case presentations provided
      by the authors to illustrate the benefits and advantages of the multidisciplinary
      team matrix in the management of patients with HCC, including the effects of this
      treatment technique on patient outcome, survival and quality of life.

PMID- 22375524
TI  - Hepatitis B-associated fibrosis and fibrosis/cirrhosis regression with nucleoside
      and nucleotide analogs.
AB  - Hepatitis B virus (HBV) infection currently accounts for approximately 600,000
      deaths per year resulting from progression of liver fibrosis to cirrhosis and
      hepatocellular carcinoma. Treatment of chronic hepatitis B with antiviral agents
      aims to improve survival through the reduction of HBV DNA to undetectable levels
      and the resultant prevention of disease progression. In recent years,
      observations in various disease areas have shown that liver fibrosis can be
      reversed if the underlying cause of the liver damage is effectively addressed. In
      line with these observations, there is now considerable evidence to suggest that
      effective sustained suppression of HBV replication with long-term anti-HBV
      treatment can result in measurable improvements in liver fibrosis over time, even
      in patients with advanced cirrhosis. This review article provides an overview of
      currently available data on regression of fibrosis and cirrhosis in patients with
      chronic hepatitis B treated with nucleoside and nucleotide analog inhibitors of
      HBV.

PMID- 22375525
TI  - Management of advanced gastric cancer.
AB  - The management of advanced gastric cancer has only evolved a little over the last
      15 years: platinum and fluoropyrimidine chemotherapy remains the backbone of
      therapy with ongoing debate as to the benefit of triplet therapy with either an
      anthracycline or taxane. Recently published trials of biological agents, in
      particular those targeting the Her2 receptor, have provided some signs of
      improvement. This article summarizes the relevant literature, discusses the role
      of these agents, as well as geographical variations in use, and provides
      recommendations regarding both 'standard chemotherapy' and the role of biological
      agents in advanced gastric cancer. Given the relative lack of progress for
      gastric cancer over the last 15 years, the focus for the next 5 years should be
      on an improved understanding of the molecular basis of gastric cancer, thus
      allowing rational integration of new molecular agents.

PMID- 22375526
TI  - Acute gastrointestinal bleeding after percutaneous coronary intervention.
AB  - Bleeding from the GI tract is a commonly encountered clinical problem after
      percutaneous coronary intervention. The GI tract is likely to become the most
      commonly encountered site of bleeding as cardiologists adopt smaller access
      sheath sizes, percutaneous closure devices and a radial artery approach, further
      reducing access-site bleeding. To appropriately manage gastrointestinal bleeding
      in this setting, the clinician must strike a balance between arresting hemorrhage
      and preventing ischemic coronary complications. To do so, an appreciation of both
      cardiovascular and gastrointestinal issues is required. This review aims to
      provide the required knowledge, as well as a series of recommendations from our
      practice, to assist in the management of this potentially fatal complication.

PMID- 22375527
TI  - The IL-23/IL-17 pathway in inflammatory bowel disease.
AB  - The etiology of inflammatory bowel disease is unknown but available evidence
      suggests that a deregulated immune response towards the commensal bacterial flora
      is responsible for intestinal inflammation in genetically predisposed
      individuals. IL-23 promotes expansion and maintenance of Th17 cells, which
      secrete the proinflammatory cytokine IL-17 and have been implicated in the
      pathogenesis of many chronic inflammatory disorders. Recent studies have shown
      that IL-23 also acts on cells of the innate immune system that can contribute to
      inflammatory cytokine production and tissue inflammation. A role for the IL-23/IL
      17 pathway in the pathogenesis of chronic intestinal inflammation in inflammatory
      bowel disease has emerged from both animal and human studies. Here we aim to
      review the recent advances in this rapidly moving field.

PMID- 22375528
TI  - Biofluid metabonomics using (1)H NMR spectroscopy: the road to biomarker
      discovery in gastroenterology and hepatology.
AB  - Metabolic profiling or 'metabonomics' is an investigatory method that allows
      metabolic changes associated with the presence of an underlying pathological
      process to be investigated. Various biofluids can be utilized in the process but
      urine, serum and fecal extract are most pertinent to the investigation of
      gastrointestinal and hepatological disease. Nuclear magnetic resonance
      spectroscopy-based metabonomic research has the potential to generate novel
      noninvasive diagnostic tests, based on biomarkers of disease, which are simple
      and cost effective yet retain high sensitivity and specificity characteristics.
      The process involves a number of key steps, including sample collection, data
      acquisition, chemometric techniques and, finally, validation. This technique
      driven review aims to demystify the metabonomics pathway, while also illustrating
      the potential of this technique with recent examples of its application in hepato
      gastroenterological disease.

PMID- 22375530
TI  - Factors affecting health-related quality of life in prostate cancer patients.
AB  - OBJECTIVE: Prostate cancer is the most common cancer among men in Lithuania.
      Quality of life (QoL) assessment plays a key role in the evaluation and treatment
      of cancer patients. The aim of this study was to evaluate factors affecting the
      QoL of patients with prostate cancer in Lithuania. MATERIAL AND METHODS: A cross
      sectional national-level study was performed. QoL was investigated with the EORTC
      QLQ-C30 questionnaire. Statistical analysis included descriptive statistics,
      interrelationship analysis between characteristics and multivariate logistic
      regression to estimate predictors and odds ratios (ORs) for each of the
      independent variables in the model. RESULTS: The response rate was 74.8% (N =
      486). One-quarter of respondents with prostate cancer indicated high QoL scores.
      Higher QoL scores were given for prostate cancer patients with lower education
      level [OR = 3.092, 95% confidence interval (CI) 1.007-9.491, p = 0.049], having
      lower monthly expenses for treatment (OR = 3.653, CI 1.318-10.128, p = 0.013),
      disease stage II (by patient conveyance) (OR = 10.053, CI 1.015-99.534, p =
      0.048), disease stage I (by medical record) (OR = 2.19E + 08, CI 218514200.17
      218514200.17, p < 0.001) and in those with undisclosed disease stage (OR = 9.220,
      CI 1.251-67.965, p = 0.029). CONCLUSIONS: Significant predictors for higher QoL
      scores were education level, own monthly expenses for treatment and disease
      stage. Patients with undisclosed disease stage more often had higher QoL scores.

PMID- 22375531
TI  - High enzymatic activity preservation with carbon nanotubes incorporated in urease
      lipid hybrid Langmuir-Blodgett films.
AB  - The search for optimized architectures, such as thin films, for the production of
      biosensors has been challenged in recent decades, and thus, the understanding of
      molecular interactions that occur at interfaces is essential to improve the
      construction of nanostructured devices. In this study, we investigated the
      possibility of using carbon nanotubes in hybrid Langmuir-Blodgett (LB) films of
      lipids and urease to improve the catalytic performance of the immobilized enzyme.
      The molecular interactions were first investigated at the air-water interface
      with the enzyme adsorbed from the aqueous subphase onto Langmuir monolayers of
      dimyristoylphosphatidic acid (DMPA). The transfer to solid supports as LB films
      and the subsequent incorporation of carbon nanotubes in the hybrid film permitted
      us to evaluate how these nanomaterials changed the physical properties of the
      ultrathin film. Colorimetric measurments indicated that the presence of nanotubes
      preserved and enhanced the enzyme activity of the film, even after 1 month. These
      results show that the use of such hybrid films is promising for the development
      of biosensors with an optimized performance.

PMID- 22375532
TI  - Micro-regional planning: evidence-based community buy-in for health development
      in five of Mexico's poorest rural districts.
AB  - BACKGROUND: Community participation was a core tenet of Primary Health Care as
      articulated in the 1970s. How this could be generated and maintained was less
      clear. This historical article describes development of protocols for evidence
      based community mobilisation in five local administrative units (municipios) in
      the Mexican state of Guerrero between 1992 and 1995. METHODS: A sample of five to
      eight sentinel sites represented each of the most impoverished municipalities of
      the poorest five of the state's seven regions. A 1992 baseline survey of
      diarrhoea and its actionable determinants provided the substrate for discussion
      with local planners and communities. Municipal planners used different strategies
      to promote participation. In one municipality, new health committees took control
      of water quality. In another, municipal authorities hired health promoters; a
      song promoted oral rehydration, and house-to-house interpersonal discussions
      promoted chlorination. In the poorest and most mountainous municipality, radio
      casera (home-made radio) soap operas used local "stars". In the largest and most
      disparate municipality, a child-to-family scheme relied on primary and secondary
      school teachers. The research team assessed outcomes at intervals and used the
      results to reinforce local planning and action. RESULTS: Diarrhoea rates declined
      in all five municipalities, and there were several positive intermediate outcomes
      from the communication strategies - changing knowledge, household practices and
      uptake of services. There was a strong link between specific contents of the
      communication package and the changing knowledge or practices. CONCLUSIONS: Apart
      from these evidence-based interventions, other factors probably contributed to
      the decline of childhood diarrhoea. But, by monitoring implementation of planning
      decisions and the impact this has at community level, micro-regional planning can
      stimulate and reinforce actions likely to improve the health of communities. The
      process empowered municipalities to get access to more resources from the state
      government and international agencies.

PMID- 22375533
TI  - Characterization of the temporary anion states on perfluoroalkanes via stabilized
      Koopmans' theorem in long-range corrected density functional theory.
AB  - The stabilized Koopmans' theorem (SKT) in long-range corrected density functional
      theory is used to characterize the temporary anion states of perfluoro-n-alkanes
      (n-PFAs) from C(2) to C(5), and perfluorocycloalkanes (c-PFAs) from C(3) to C(4).
      In this approach, stabilization is accomplished by varying the exponents of
      appropriate diffuse functions. The energies of temporary anion states are then
      identified by investigating the relationship between the resultant eigenvalues
      and scale parameter. The characteristics of resonance orbitals are also examined.
      For the lowest unfilled orbitals of perfluoroalkanes, results indicate that they
      are mainly from the pi-bonding interactions between all neighboring C atoms. In
      addition, their energies decrease as the sizes of the perfluoroalkanes increase.
      Moreover, the energies of the c-C(3)F(6)/c-C(4)F(8) are lower than those of the
      corresponding n-C(3)F(8)/n-C(4)F(10). When compared with experimental data, our
      SKT calculations can yield conformable results. Thus, this SKT approach can
      provide more information on the resonance states of perfluoroalkanes.

PMID- 22375534
TI  - Comprehensive sediment toxicity assessment of Hessian surface waters using
      Lumbriculus variegatus and Chironomus riparius.
AB  - The objective of this study was a sediment assessment of predominantly small
      rivers in the German federal state of Hesse. For this purpose, sediment samples
      were taken at 50 study sites with different contamination levels. The benthic
      invertebrates Chironomus riparius (Diptera) and Lumbriculus variegatus
      (Oligochaeta) were used as test species and exposed to whole sediments in chronic
      laboratory experiments. The bioassays were carried out on the basis of OECD
      guidelines 218 and 225 for the testing of chemicals. For about 50 % of the study
      sites chemical analytical data for pollutants from environmentally important
      substance classes like metals, polycyclic aromatic hydrocarbons, polychlorinated
      biphenyls, and organotin compounds were available. These data were used to
      analyze correlations between effects in the bioassays and measured chemical
      contaminations at sampling sites. For 22 % of the sediments ecologically relevant
      adverse effects were observed. In the majority of these cases effects occurred in
      only one of the biotests, and only one sediment sample exerted a negative effect
      on both test organisms. There was no significant correlation between biological
      responses and chemical data considering substance classes. However, there was a
      weak positive correlation between arsenic concentration and both worm number and
      worm biomass as well as a weak positive correlation between single PAHs and worm
      biomass. In some sediment tests elevated ammonia concentrations occurred in the
      overlying water so that an influence of these partially toxic concentrations on
      the test results cannot be ruled out.

PMID- 22375535
TI  - Combined chemical oxidation and membrane filtration techniques applied to the
      removal of some selected pharmaceuticals from water systems.
AB  - The elimination of five selected pharmaceuticals (amoxicillin,
      hydrochlorothiazide, metoprolol, naproxen and phenacetin) dissolved in different
      water systems (two natural water matrices and a secondary effluent) was carried
      out by sequential processes constituted by membrane filtration and chemical
      oxidation stages. Different configurations of those two stages were applied. In a
      first group, a pretreatment consisting in a membrane filtration (ultrafiltration
      or nanofiltration) was conducted; and the permeate and retentate effluents
      produced were afterwards treated by chemical oxidation, using ozone or chlorine.
      In a second group, the pretreatment consisted in a chemical oxidation stage (by
      using ozone, chlorine, O(3)/H(2)O(2), UV or UV/H(2)O(2)) followed by a
      nanofiltration process. The main objective of this set of experiments was the
      comparison of the efficiencies reached by using different systems and
      configurations in order to optimize the elimination of those pollutants from the
      selected water matrices. Results of removals and rejection coefficients for the
      five pharmaceuticals showed that the combined treatments involving UV radiation
      (254 nm monochromatic radiation during 30 min) followed by nanofiltration were
      very effective, with global removals over 80 % in most of the experiments.
      Ozonation (initial dose of 2.25 mg L(-1)) followed by nanofiltration also showed
      high levels of efficiency, with removals over 70 % in the permeate stream
      generated in experiments carried out with natural waters. The opposite sequence,
      nanofiltration followed by ozonation, reached removals over 97 % in the natural
      waters by using an ozone dose of 2.25 mg L(-1); and over 90 % in the secondary
      effluent with an initial ozone dose of 3.75 mg L(-1).

PMID- 22375536
TI  - Impact of chromium and aluminium pollution on the diversity of zooplankton: a
      case study in the Chimaliapan wetland (Ramsar site) (Lerma basin, Mexico).
AB  - Biological monitoring and the use of biotic indices are important in evaluating
      the health of aquatic systems. However, zooplankton are rarely included in
      biomonitoring protocols. We conducted a one-year study (March 2008-February 2009)
      at two sites from the Chimaliapan wetland, with concentrations of aluminium (Al)
      and chromium (Cr) above and within the permissible limits, respectively. Metals
      in the sediment and water were analyzed from three locations per site every two
      months. In addition to analyses of the abundance and diversity of rotifers,
      cladocerans and copepods, we sampled 11 physicochemical variables in the water
      and six from the sediments. The metal concentration in the polluted site
      (significantly above the permissible limits) ranged between 7266-8174 mg Kg(-1)
      of Al and 14.6-18.3 mg Kg(-1) of Cr. We found 92 species of rotifers, cladocerans
      and copepods. The Brillouin index for both sites ranged from 3.9-5.4, the Shannon
      Wiener index from 4.2-5.5 while the Brachionus-Trichocerca ratio ranged between
      1.0 and 1.7. The Wetland Zooplankton Index was significantly different among the
      sites; 2.63 at site 1 and 2.13 at site 2. The saprobic index was 3.2 for both
      sites. Data analyses using multifactorial techniques suggested that zooplankton
      can be used to evaluate the impact of the metals aforementioned, since these
      organisms are generally more sensitive than other groups and also have a high
      ecological relevance.

PMID- 22375537
TI  - Physiological and morphological changes in Salix viminalis L. as a result of
      plant exposure to copper.
AB  - The aim of this study was to assess the response of Salix viminalis L. under
      model conditions to different copper concentrations and, as a consequence,
      potential application of the experimental results in decontamination of water
      with heavy metal ions (phytoaccumlation). The 14-day experiment was conducted on
      one-year-old cuttings of Salix viminalis L. 'Cannabina' exposed, in a phytotron,
      to six different copper levels in hydroponic pots. The results showed that the
      capacity to accumulate heavy metals was of the following order: roots > rods >
      shoots > leaves. The linear relationships between the accumulation efficiency of
      particular Salix parts were confirmed. Together with an increase in copper
      sorption in above-ground organs, a decrease was observed in root biomass and the
      length of roots, shoots and leaves. The release of low molecular weight organic
      acids into solution was different under various Cu levels. Glucose, fructose and
      sucrose contents in leaves of Salix in all treatments were higher than in control
      plants. Higher concentration of sugars (4 times higher compared to the control)
      was detected for fructose in a 2 mM Cu treatment. The total phenolics content
      rapidly increased only at 3 mM Cu level. Free and total salicylic acid and the
      glutathione contents in plants treated with copper in relation to the control
      were always higher and changed with increasing concentration of copper ions in
      the medium.

PMID- 22375538
TI  - Remediation of saline soil from shrimp farms by three different plants including
      soybean (Glycine max (L.) Merr.).
AB  - Shrimp farm activity can elevate in-situ soil salinity that in turn may affect
      any subsequent crop production if land usage changes. The utility of three
      different plants viz. soybean (Glycine max (L.) Merr.), narrow leaf cat-tail
      (Typha angustifolia L.) and sea holly (Acanthus ebracteatus Vahl) for
      phytoremediation of saline soil derived from former shrimp farm activity was
      investigated. The latter two species have been categorized as halophytes. In
      experiments of 16 days' duration and using sodium chloride concentrations (50-70
      mg g(-1) dry weight) similar to those found in the benthic material of shrimp
      farms in Nakhon Pathom Province, central Thailand, the bioconcentration factors
      of sodium chloride (BCF; g soil dry weight g(-1) plant dry weight) in soybean
      (2240-4840) were found to be significantly higher than those found for narrow
      leaf cat-tail (16-20) and sea holly (15-17) at p < 0.05. The translocation of
      sodium chloride from root to shoot was noted in all plant species investigated,
      as well as wilting and defoliation due to the effects of sodium chloride.
      Approximately 90 %, 70 % and 60 % removal of sodium chloride in root zone soil
      was observed after growing soybean, narrow leaf cat-tail and sea holly,
      respectively. Soybean plants thus showed the greatest ability to decrease soil
      salinity, with measured root zone soil conductivity levels falling from 16.4-18
      dS m(-1) (characteristic of strongly saline soils) to 1.5- 2.1 dS m(-1) (weakly
      saline). Although an important economic crop, soybean may also have potential in
      soil remediation.

PMID- 22375539
TI  - Influence of the organic loading rate on the growth of Galactomyces geotrichum in
      activated sludge.
AB  - Recent studies reporting on the useful implementation of fungi in wastewater
      treatment plants triggered the need to improve fungi based systems. Therefore, it
      is crucial to investigate the conditions that promote their selection. The
      present work aims to study the effect of the organic loading rate on the growth
      of filamentous fungi. Three sequencing batch reactors (SBR), fed with an easily
      biodegradable substrate (acetate), were operated at different organic loading
      rates: 4.3 g COD L(-1) day(-1) (SBR1), 1.0 g COD L(-1) day(-1) (SBR2) and 0.5 g
      COD L(-1) day(-1) (SBR3). High amounts of fungal filaments were observed in the
      SBR operating at higher organic loading rate, as ascertained by direct
      microscopic inspection, while, at lower organic loading rates, overabundance of
      fungal filaments was not observed. Sequence retrieved from the isolated fungal
      filaments presented high similarity (99 %) to Galactomyces geotrichum.

PMID- 22375540
TI  - Facile preparation of magnetic C/TiO2/Ni composites and their photocatalytic
      performance for removal of a dye from water under UV light irradiation.
AB  - Development of a photocatalyst with high efficiency and separability is still a
      challenging task in the field of wastewater treatment. In this study, new
      magnetic separable C/TiO(2)/Ni composite as a photocatalyst was prepared by a
      facile pyrolysis reaction, using powdered activated carbon (PAC), TiO(2) and
      Ni(Ac)(2) as precursors. The results proved that the photocatalyst (C/TiO(2)/Ni)
      synthesized in this work exhibited greater removal activity for Methyl Orange
      (MO) dye from water as compared with the commercially available well reported
      TiO(2) nanoparticles (P25). This significant enhancement in the photocatalytic
      activity for wastewater treatment due to the combination of PAC and TiO(2) could
      be presumed as the synergetic effect on the contacting interface of TiO(2) and
      PAC, and such effect was initially demonstrated by electrochemical impedance
      measurements. Furthermore, the trait that it consists of magnetic properties and
      therefore is easy to be recycled, which could be harnessed by an external magnet
      and may have many advantages over pure metal oxides (like TiO(2)) especially in
      the industrial procedures.

PMID- 22375541
TI  - Zinc oxide nanoparticles cause nephrotoxicity and kidney metabolism alterations
      in rats.
AB  - Although zinc oxide nanoparticles (ZnO NPs) have been widely used, their
      potential hazards on mammalian and human remain largely unknown. In this study,
      the biochemical compositions of urine and kidney from the rats treated with ZnO
      NPs (100, 300 and 1000 mg/kg, respectively) were investigated using (1)H nuclear
      magnetic resonance (NMR) technique with the pattern recognition of partial least
      squares-discriminant analysis. Hematology, clinical biochemistry and kidney
      histopathological examinations were also performed. Metabolic profiles from rats
      treated with ZnO NP(S) exhibited increases in the levels of taurine, lactate,
      acetate, creatine, phosphocholine, trimethylamine-N-oxide, alpha-glucose, and 3-D
      hydroxybutyrate, as well as decreases in lipid, succinate, citrate, alpha
      ketoglutarate, hippurate and 4-hydroxyphenylacetic acid in urine after ZnO NPs
      treatment for 14 days. A similar alteration pattern was also identified in
      kidney. Urine choline and phosphocholine increased significantly shortly after
      ZnO NPs treatment, moreover, some amino acids and glucose also increased during
      the experimental period. However, succinate, citrate and alpha-ketoglutarate in
      urine exhibited a different alteration trend, which showed increases on the first
      day after ZnO NPs treatment, but decreases gradually until the termination of the
      study. A similar alteration pattern of urinary (1)H NMR spectra was also detected
      in kidney. Moreover, ZnO NPs (1000 mg/kg) resulted in significant increases in
      serum creatine and blood urea nitrogen, decreases in hemoglobin, haematocrit and
      mean corpuscular hemoglobin concentration, and overt tubular epithelial cell
      necrosis. These findings show that ZnO NPs can disturb the energy metabolism and
      cause mitochondria and cell membrane impairment in rat kidney, which may
      contribute to ZnO NPs-induced nephrotoxicity.

PMID- 22375542
TI  - Assessment of the quality and toxicity of the discharges of a wastewater
      treatment plant and alternatives to improve its operation.
AB  - Wastewater discharges into freshwater bodies represent a serious ecological
      problem worldwide. In underdeveloped and developing countries wastewater
      treatment plants (WTP) only count with basic treatment, leading to the pollution
      of important aquatic reservoirs causing critical situations. In the present work,
      a one year evaluation of toxicity and main physical and chemical parameters of
      one of the major WTP of the state of Aguascalientes was conducted fortnightly,
      and to assess treatment alternatives for this WTP we tested: a) three white rot
      fungi (WRF), b) a photo-electrochemical process, c) ion-exchangers resins and
      activated carbon. The 3 WRF exhibited high COD removal from influents (72 - 95 %)
      but only Phanerochaete chrysosporium reached significant toxicity removals (70
      and 55 %, for an influent and an effluent, respectively). Treatments with
      electrochemical advanced oxidation processes resulted with the highest toxicity
      and COD removals (96 % for both parameters) in comparison to biological and
      physicochemical treatments. Adsorption with activated carbon, zeolite and chelex
      ion-exchange resins removed 60 - 90 % of COD and 60 - 99 % toxicity. These
      results could be used to improve operation of the Industrial Park WTP and to plan
      future modifications to the plant.

PMID- 22375543
TI  - Aeration prevents methyl mercury production in dental wastewater.
AB  - Although research has demonstrated that Hg is methylated in the reducing
      conditions of the dental clinic wastewater collection system, studies are
      inconclusive as to whether further methylation occurs in the aeration basin of
      activated sludge wastewater treatment plant (WWTP) which typically treats this
      waste. Given the high levels of methyl Hg reported in dental wastewater (DWW), it
      is important to determine whether additional methylation occurs once it enters
      the WWTP. To achieve this objective, we incubated DWW under conditions designed
      to mimic the oxidized conditions of the activated sludge aeration basin in a
      WWTP. Duplicate bioreactors were charged with raw DWW collected from a 12-chair
      dental clinic and incubated both with and without aeration. Aeration was
      continued for 15 days, consistent with the typical mean cell residence time
      (MCRT) necessary for both heterotrophic carbon oxidation (typically 5-6 days) and
      nitrification (typically 12-15 days), thus ensuring that incubation time exceeded
      those for most conceivable MCRTs used in the activated sludge process. Results
      demonstrate a rapid increase in pH concomitant with an increase in dissolved
      oxygen (DO) to near saturation in the aerated reactor. The non-aerated reactor
      remained low or at zero DO due to low surface reaeration coupled with the high
      levels of organic matter. The rate of mercury methylation increased in the
      unaearated reactors rapidly upon incubation, reaching highest levels when DO was
      at the lowest levels during the experiment. In great contrast, methyl mercury
      levels were much lower and net mercury methylation does not appear to occur at
      any significant rate under aeration. These results imply that although some
      mercury methylation may occur in the sewer collection system (or anaerobic
      digesters), net methylation is unlikely to occur in the aeration basin in
      activated sludge WWTPs, and thus methyl Hg influent levels from DWW represent an
      upper bound on effluent levels.

PMID- 22375544
TI  - Temperature and moisture effect on spore emission in the fungal biofiltration of
      hydrophobic VOCs.
AB  - The effect of temperature and moisture on the elimination capacity (EC), CO(2)
      production and spore emission by Fusarium solani was studied in biofilters packed
      with vermiculite and fed with n- pentane. Three temperatures (15, 25 and 35
      degrees C) were tested and the highest average EC (64 g m(-3) h(-1)) and lower
      emission of spores (2.0 * 10(3) CFU m(-3) air) were obtained at 25 degrees C. The
      effect of moisture content of the packing material indicates that the highest EC
      (65 g m(-3) h(-1)) was obtained at 50 % moisture. However, lowest emission (1.3 *
      10(3) CFU m(-3) air) was obtained at 80 % moisture. Furthermore, the results show
      that a slight decrease in spore emission was found with increasing moisture
      content. In all cases, the depletion of the nitrogen source in the biofilter
      induced the sporulation, a decay of the EC and increased spore emission.

PMID- 22375545
TI  - Mercury in soil and perennial plants in a mining-affected urban area from
      Northwestern Romania.
AB  - The mercury (Hg) concentrations were evaluated in soils and perennial plants
      sampled in four districts of Baia Mare city, a historical mining and ore
      processing center in Northwestern Romania. The results showed that the Hg
      concentration exceeded the guideline value of 1.0 mg kg(-1) dry weight (dw)
      established by the Romanian Legislation, in 24 % of the analyzed soil samples,
      while the median Hg concentration (0.70 mg kg(-1) dw) was lower than the
      guideline value. However, Hg content in soil was generally higher than typical
      values in soils from residential and agricultural areas of the cities all over
      the world. The median Hg concentration was 0.22 mg kg(-1) dw in the perennial
      plants, and exceeded the maximum level of Hg (0.10 mg kg(-1)) established by
      European Directive 2002/32/EC for plants used in animal feed in order to prevent
      its transfer and further accumulation in the higher levels of food chain. No
      significant correlations were found between soil Hg and other analyzed metals
      (Cd, Cu, Pb, Zn) resulted from the non-ferrous smelting activities, probably due
      to the different physicochemical properties, that led to different dispersion
      patterns.

PMID- 22375546
TI  - Uranium and other heavy metal resistance and accumulation in bacteria isolated
      from uranium mine wastes.
AB  - Ten bacterial strains isolated from uranium mine wastes were characterized in
      terms of their uranium and other metal resistance and accumulation. 16S rRNA gene
      sequence analysis identified the strains as members of genera Bacillus, Serratia,
      and Arthrobacter. Strains were able to utilize various carbon sources,
      particularly aromatic hydrocarbons, grow at broad pH and temperature ranges and
      produce non specific acid phosphatase relevant for metal phosphate precipitation
      in contaminated environment. The isolates exhibited high uranium and other heavy
      metals (Ni, Co, Cu and Cd) resistance and accumulation capacities. Particularly,
      Arthrobacter sp. J001 and Bacillus sp. J003 were superior in terms of U
      resistance at low pH (pH 4.0) along with metals and actinides (U and Th) removal
      with maximum cell loading of 1088 MUmol U, 1293 MUmol Th, 425 MUmol Cu, 305 MUmol
      Cd, 377 MUmol Zn, 250 MUmol Ni g(-1) cell dry wt. Genes encoding P(1B)-type
      ATPases (Cu-CPx and Zn-CPx) and ABC transporters (nik) as catalytic tools for
      maintaining cellular metal homeostasis were detected within several Bacillus
      spp., with possible incidence of horizontal gene transfer for the later gene
      showing phylogenetic lineage to alpha Proteobacteria members. The study provides
      evidence on intrinsic abilities of indigenous bacteria from U-mine suitable for
      survival and cleaning up of contaminated mine sites.

PMID- 22375547
TI  - Effect of carbon sources on the removal of 1,1,2-trichloroethane and 1,1,2,2
      tetrachloroethane in UASB reactor.
AB  - The effect of two carbon sources namely sodium acetate and ethanol was studied in
      bench-scale Upflow Anaerobic Sludge Blanket (UASB) reactors for the removal of
      chlorinated ethanes i.e., 1,1,2-Trichloroethane (TCA) and 1,1,2,2
      Tetrachloroethane (TeCA) contained in the simulated wastewaters. The Hydraulic
      Retention Time (HRT) was maintained as 24 hours in all the reactors. The granular
      biomass in the test reactors R2 and R3 were acclimated to 40 mg/L of TCA and 20
      mg/L of TeCA, respectively. The effluent TCA and TeCA concentrations were 0.03
      mg/L and 0.18 mg/L, respectively, at the end of acclimation phase. Sodium acetate
      and ethanol both were found to be suitable as the primary substrates in the
      biodegradation of TCA and TeCA. However, lower concentrations of the toxic
      pollutants (TCA and TeCA) were obtained in the effluents with the use of sodium
      acetate. The COD removal efficiency in the test reactors (R2 and R3) varied in
      the range of 95 % to 98.2 % accompanied by the formation of 1,2-Dichloroethane
      (DCA) as the major intermediate.

PMID- 22375548
TI  - Moss biomonitoring of air pollution with heavy metals in the vicinity of a
      ferronickel smelter plant.
AB  - The purpose of this study was to establish the atmospheric deposition of various
      elements in the Kavadarci region, Republic of Macedonia (known for its
      ferronickel mining and metallurgical activities) using moss biomonitoring, and to
      determine whether the deposition is anthropogenic or from geogenic influences.
      The sampling network includes 31 moss samples evenly distributed over a territory
      of about 600 km(2). A total of 46 elements (Ag, Al, As, Au, Ba, Be, Ca, Cd, Ce,
      Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hg, Ho, K, La, Li, Lu, Mg, Mn, Mo,
      Na, Nb, Ni, P, Pb, Rb, Sb, Sm, Sr, Tb, Th, Ti, U, V, Yb, Zn, Zr) were determined
      by mass spectrometry with inductively coupled plasma (ICP-MS). Based on a
      distribution pattern of elements determined in moss, two anthropogenic
      geochemical associations (Co-Cr-Cu-Fe-Mg-Ni and As-Cd-Cu-Hg-Pb-Zn), were
      detected. The distribution of these elements shows an increased content
      (especially Ni, Co and Cr) in the moss samples from the surroundings of the
      smelter plant compared to the rest of the samples. Thus, the median value of Ni
      in moss samples from the whole region (40 mg kg(-1)) is much higher than the
      median for Macedonia (5.82 mg kg(-1)). Moreover, the median content of Ni in the
      moss samples from the polluted area (around the smelter) is 178 mg kg(-1) with an
      enrichment ratio in the moss samples of almost 5.5 times higher than the
      unpolluted areas (32 mg kg(-1)). This fact confirms the influence of the dust
      from the ferronickel plant to the air pollution in this region.

PMID- 22375549
TI  - Hydrocortisone and long-term outcomes in very-low-birthweight infants.
AB  - BACKGROUND: The long-term effects of hydrocortisone (HDC) used for very-low
      birthweight (VLBW) infants with chronic lung disease (CLD) are not fully
      understood. The aim of this study was to examine the short-term clinical effects
      and long-term impact of a physiological replacement dose of HDC on acute
      deterioration of CLD in VLBW infants. METHODS: This prospective case-control
      study included 110 of the 174 VLBW infants admitted to our facility between 2003
      and 2006 who were followed up to a corrected age of 18 months. Infant deaths and
      infants with congenital deformities were excluded from the study. The infants
      were classified into the following three groups: infants with CLD and treated
      with HDC (1-2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD
      treatment group; n = 24); infants with CLD but not treated with HDC (CLD
      untreated group; n = 40); and infants without CLD (non-CLD group; n = 46).
      RESULTS: The fraction of inspired oxygen (F(I) O(2) ) in the CLD treatment group
      improved significantly after treatment (P < 0.01). There were no significant
      differences among the three groups in terms of growth and neurodevelopmental
      quotient at the corrected age of 18 months following adjustment for birthweight,
      sex, and presence of light-for-date infants. There were also no significant
      intergroup differences in all three areas of developmental quotient. CONCLUSIONS:
      Physiological doses of HDC replacement are effective in treating acute
      deterioration in oxygenation in VLBW infants with CLD. Furthermore, this
      treatment modality did not adversely affect the growth and development of infants
      at the corrected age of 18 months.

PMID- 22375550
TI  - Next-generation sequencing: ready for the clinics?
AB  - Next-generation sequencing (NGS) has transformed genomic research by decreasing
      the cost of sequencing and increasing the throughput. Now, the focus is on using
      NGS technology for diagnostics and therapeutics. In this review, we discuss the
      possible clinical applications of NGS and the potential of some of the current
      systems to transition to the clinic. Clinical use of NGS technologies will enable
      the identification of causative mutations for rare genetic disorders through
      whole-genome or targeted genome resequencing, rapid pathogen screening and cancer
      diagnosis along with the identification of appropriate therapy. Routine clinical
      use of NGS technologies is appealing, but mandates high accuracy, simple assays,
      small inexpensive instruments, flexible throughput, short run times and most
      importantly, easy data analysis as well as interpretation. A number of NGS
      systems launched recently have least some of these characteristics, namely, small
      instruments, flexible throughput and short run time, but still face a few
      challenges. Moreover, simplified data analysis tools will need to be developed to
      minimize the requirement of sophisticated bioinformatics support in clinics. In
      summary, for successful transition of NGS to clinic, a sustained collaboration
      between research labs, clinical practitioners and vendors offering sequencing
      based genetic tests is required.

PMID- 22375551
TI  - Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen
      complexes via reduction of oxidative stress.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH), a progressive stage of
      nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis
      (accumulation of triacylglycerols within hepatocytes) along with inflammation and
      ballooning degeneration. It has been suggested that oxidative stress may play an
      important role in the progress of NAFLD to NASH. The aim of present study was to
      determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C
      could improve the biochemical and histological abnormalities associated with diet
      induced NASH in rats. METHODS: NASH was induced in male N-Mary rats by feeding a
      methionine - choline deficient (MCD) diet. The rats were fed either normal chow
      or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly
      divided into four groups of six: the NASH group that received MCD diet, the EUK-8
      group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet
      plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK
      8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage
      for eight weeks. RESULTS: Treatment of MCD-fed rats with salens reduced the sera
      aminotransferases, cholesterol, low density lipoprotein contents, the extent of
      lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels
      were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis,
      ballooning degeneration and inflammation in liver of MCD-fed rats. CONCLUSION:
      Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced
      biochemical and histological abnormalities, pointing out that antioxidant
      strategy could be beneficial in treatment of NASH.

PMID- 22375552
TI  - Isoform-selective induction of human p110delta PI3K expression by TNFalpha:
      identification of a new and inducible PIK3CD promoter.
AB  - PI3Ks (phosphoinositide 3-kinases) are signalling molecules and drug targets with
      important biological functions, yet the regulation of PI3K gene expression is
      poorly understood. Key PI3Ks are the class IA PI3Ks that consist of a catalytic
      subunit (p110alpha, p110beta and p110delta) in complex with a p85 regulatory
      subunit. Whereas p110alpha and p110beta are ubiquitously expressed, high levels
      of p110delta are mainly found in white blood cells, with most non-leucocytes
      expressing low levels of p110delta. In the present paper we report that TNFalpha
      (tumour necrosis factor alpha) stimulation induces p110delta expression in human
      ECs (endothelial cells) and synovial fibroblasts, but not in leucocytes, through
      transcription start sites located in a novel promoter region in the p110delta
      gene (PIK3CD). This promoter is used in all cell types, including solid tumour
      cell lines that express p110delta, and is activated by TNFalpha in ECs and
      synovial fibroblasts. We further present a detailed biochemical and bioinformatic
      characterization of p110delta gene regulation, demonstrating that PIK3CD has
      distinct promoters, some of which can be dynamically activated by pro
      inflammatory mediators. This is the first molecular identification of a PI3K
      promoter under the control of acute extracellular stimulation.

PMID- 22375553
TI  - Against quantiles: categorization of continuous variables in epidemiologic
      research, and its discontents.
AB  - BACKGROUND: Quantiles are a staple of epidemiologic research: in contemporary
      epidemiologic practice, continuous variables are typically categorized into
      tertiles, quartiles and quintiles as a means to illustrate the relationship
      between a continuous exposure and a binary outcome. DISCUSSION: In this paper we
      argue that this approach is highly problematic and present several potential
      alternatives. We also discuss the perceived drawbacks of these newer statistical
      methods and the possible reasons for their slow adoption by epidemiologists.
      SUMMARY: The use of quantiles is often inadequate for epidemiologic research with
      continuous variables.

PMID- 22375556
TI  - X chromosome inactivation in women with alcoholism.
AB  - BACKGROUND: All female mammals with 2 X chromosomes balance gene expression with
      males having only 1 X by inactivating one of their X chromosomes (X chromosome
      inactivation [XCI]). Analysis of XCI in females offers the opportunity to
      investigate both X-linked genetic factors and early embryonic development that
      may contribute to alcoholism. Increases in the prevalence of skewing of XCI in
      women with alcoholism could implicate biological risk factors. METHODS: The
      pattern of XCI was examined in DNA isolated in blood from 44 adult women meeting
      DSM-IV criteria for an alcohol use disorder and 45 control women with no known
      history of alcohol abuse or dependence. XCI status was determined by analyzing
      digested and undigested polymerase chain reaction (PCR) products of the
      polymorphic androgen receptor (AR) gene located on the X chromosome. Subjects
      were categorized into 3 groups based upon the degree of XCI skewness: random
      (50:50 to 64:36%), moderately skewed (65:35 to 80:20%), and highly skewed
      (>80:20%). RESULTS: XCI status from informative women with alcoholism was found
      to be random in 59% (n = 26), moderately skewed in 27% (n = 12), or highly skewed
      in 14% (n = 6). Control subjects showed 60, 29, and 11%, respectively. The
      distribution of skewed XCI observed among women with alcoholism did not differ
      statistically from that of control subjects (chi(2) test = 0.14, 2 df, p = 0.93).
      CONCLUSIONS: Our data did not support an increase in XCI skewness among women
      with alcoholism or implicate early developmental events associated with embryonic
      cell loss or unequal (nonrandom) expression of X-linked gene(s) or defects in
      alcoholism among women.

PMID- 22375557
TI  - Epigenetics: a way to understand the origin and biology of testicular germ cell
      tumors.
AB  - Testicular germ cell tumors are neoplasms carrying two unique features. First,
      testicular germ cell tumors have a pluripotential nature and show protean
      histology ranging from that of germ cells to embryonal and differentiated somatic
      cells. Therefore, testicular germ cell tumors are interesting resources
      positioned at a crossroad in developmental and neoplastic processes. The second
      unique feature of testicular germ cell tumors is their exquisite sensitivity to
      cisplatin-based chemotherapy. This review summarizes recent research progress in
      the epigenetics of testicular germ cell tumors in an attempt to explain the
      abovementioned biological and clinical characteristics of testicular germ cell
      tumors.

PMID- 22375558
TI  - Preparing or executing the wrong task: the influence on switch effects.
AB  - In a previous study, it was proposed that executing a task leads to task
      strengthening. In other words, task activation at the moment of response
      execution determines subsequent switch effects (Steinhauser & Hubner, 2006). The
      authors investigated this issue by comparing switch effects after task and
      response errors. However, the use of bivalent stimulus-response mappings might
      have obscured some of the effects. Therefore, we replicated the experiment using
      univalent stimulus-response mappings. With this adjusted design, which overcomes
      some shortcomings of the original study, we were able to replicate the finding of
      switch benefits after task errors. Closer inspection of the data showed the
      importance of preexecution processes on subsequent switch effects. In a second
      experiment, we further elaborated on these preexecution processes. More
      precisely, we investigated the effect of task preparation on subsequent switch
      effects. Taken together, our data extend current accounts of task switching by
      showing that the preparatory processes occurring before the response on trial n
      influence the switch cost on trial n + 1.

PMID- 22375559
TI  - Physical microscopic model of proteins under force.
AB  - Nature has evolved proteins to counteract forces applied on living cells, and has
      designed proteins that can sense forces. One can appreciate Nature's ingenuity in
      evolving these proteins to be highly sensitive to force and to have a high
      dynamic force range at which they operate. To achieve this level of sensitivity,
      many of these proteins are composed of multiple domains and linking peptides
      connecting these domains, each of them having their own force response regimes.
      Here, using a simple model of a protein, we address the question of how each
      individual domain responds to force. We also ask how multidomain proteins respond
      to forces. We find that the end-to-end distance of individual domains under force
      scales linearly with force. In multidomain proteins, we find that the force
      response has a rich range: at low force, extension is predominantly governed by
      "weaker" linking peptides or domain intermediates, while at higher force, the
      extension is governed by unfolding of individual domains. Overall, the force
      extension curve comprises multiple sigmoidal transitions governed by unfolding of
      linking peptides and domains. Our study provides a basic framework for the
      understanding of protein response to force, and allows for interpretation
      experiments in which force is used to study the mechanical properties of
      multidomain proteins.

PMID- 22375560
TI  - Tuning structural and mechanical properties of two-dimensional molecular
      crystals: the roles of carbon side chains.
AB  - A key requirement for the future applicability of molecular electronics devices
      is a resilience of their properties to mechanical deformation. At present,
      however, there is no fundamental understanding of the origins of mechanical
      properties of molecular films. Here we use quinacridone, which possesses flexible
      carbon side chains, as a model molecular system to address this issue. Eight
      molecular configurations with different molecular coverage are identified by
      scanning tunneling microscopy. Theoretical calculations reveal quantitatively the
      roles of different molecule-molecule and molecule-substrate interactions and
      predict the observed sequence of configurations. Remarkably, we find that a
      single Young's modulus applies for all configurations, the magnitude of which is
      controlled by side chain length, suggesting a versatile avenue for tuning not
      only the physical and chemical properties of molecular films but also their
      elastic properties.

PMID- 22375561
TI  - Working with young adults with Type 1 diabetes: views of a multidisciplinary care
      team and implications for service delivery.
AB  - AIMS: Young adults with Type 1 diabetes experience difficulties achieving glucose
      targets. Clinic attendance can be poor, although health and self-care tend to be
      better among those who attend regularly. Our aims were to describe staff views
      about challenges working with this age-group (16-21 years). METHODS:
      Semistructured interviews were conducted with 14 staff from Sheffield Teaching
      Hospitals diabetes care team. Interviews were audio-recorded, transcribed and
      analysed using thematic analysis. RESULTS: Three main themes emerged. Unique
      challenges working with young adults included staff emotional burden, the low
      priority given to self-care by young adults and the complexity of the diabetes
      regimen. Working in a multidisciplinary team was complicated by differences in
      consultation styles, poor team cohesion and communication. An ideal service
      should include psychological support for the professional team, identification of
      key workers, and development of individualized care plans. CONCLUSIONS: Staff
      differed in their views about how to achieve optimal management for young adults,
      but emphasized the need for greater patient-centred care and a range of
      interventions appropriate for individual levels of need. They also wanted to
      increase their own skills and confidence working with this age-group. While these
      results reflect the views of staff working in only one diabetes centre, they are
      likely to reflect the views of professionals delivering care to individuals of
      this age; replication is needed to determine their generalizability.

PMID- 22375562
TI  - Targeted interventions of the Avahan program and their association with
      intermediate outcomes among female sex workers in Maharashtra, India.
AB  - BACKGROUND: Avahan, the India AIDS Initiative has been a partner supporting
      targeted interventions of high risk populations under India's National AIDS
      Control Organisation (NACO) since 2004 in the state of Maharashtra. This paper
      presents an assessment of the Avahan program among female sex workers (FSWs) in
      Maharashtra, its coverage, outcomes achieved and their association with Avahan
      program. METHODS: An analytical framework based on the Avahan evaluation design
      was used, addressing assessment questions on program implementation, intermediate
      outcomes and association of outcomes with Avahan. Data from routine program
      monitoring, two rounds of cross-sectional Integrated Behavioural and Biological
      Assessments (IBBAs) conducted in 2006 (Round 1- R1) and 2009 (Round 2 - R2) and
      quality assessments of program clinics were used. Bi-variate and multivariate
      analysis were conducted using the complex samples module in SPSS 15 (IBM, Somers
      NY). RESULTS: The Avahan program achieved coverage of over 66% of FSWs within
      four years of implementation. The IBBA data showed increased contact by peers in
      R2 compared to R1 (AOR:2.34; p=0.001). Reported condom use with clients increased
      in R2 and number of FSWs reporting zero unprotected sex acts increased from 76.2%
      (R1) to 94.6% (R2) [AOR: 5.1, p=0.001].Significant declines were observed in
      prevalence of syphilis (RPR) (15.8% to 10.8%; AOR:0.54; p=0.001), chlamydia (8%
      to 6.2%; AOR:.0.65; p=0.010) and gonorrohoea (7.4% to 3.9; AOR:.0.60; p=0.026)
      between R1 and R2. HIV prevalence increased (25.8% to 27.5%; AOR:1.29; p=0.04).
      District-wise analysis showed decline in three districts and increase in Mumbai
      and Thane districts.FSWs exposed to Avahan had higher consistent condom use with
      occasional (94.3% vs. 90.6%; AOR: 1.55; p=0.04) and regular clients (92.5% vs.
      86.0%; AOR: 1.95, p=0.001) compared to FSWs unexposed to Avahan. Decline in high
      titre syphilis was associated with Avahan exposure. CONCLUSION: The Avahan
      program was scaled up and achieved high coverage of FSWs in Maharashtra amidst
      multiple intervention players. Avahan coverage of FSWs was associated with
      improved safe sexual practices and declines in STIs. Prevalence of HIV increased
      requiring more detailed understanding of the data and, if confirmed, new
      approaches for HIV control.

PMID- 22375564
TI  - Poor maternal nutrition programmes a pro-atherosclerotic phenotype in ApoE-/-
      mice.
AB  - Numerous animal studies have consistently shown that early life exposure to LP
      (low-protein) diet programmes risk factors for CVD (cardiovascular disease) such
      as dyslipidaemia, high BP (blood pressure) and cardiac dysfunction in the
      offspring. However, studies on the effect of maternal under-nutrition on
      offspring development of atherosclerosis are scarce. Applying our LP model to the
      ApoE(-/-) atherosclerosis-prone mouse model, we investigated the development of
      atherosclerotic lesions in the aortic root of 6-month-old offspring. In addition,
      markers of plaque progression including SMA (smooth muscle actin) and Mac3
      (macrophage marker 3) were studied. Pregnant dams were fed on a control (20%
      protein) or on an isocaloric LP diet (8% protein) throughout pregnancy and
      lactation. After weaning, male offspring were maintained on 20% normal laboratory
      chow. At 6 months of age, LP offspring showed a significantly greater plaque area
      (P<0.05) with increased cholesterol clefts and significantly higher indices of
      DNA damage compared with controls (P<0.05). The expression of HMG-CoA reductase
      (3-hydroxy-3-methyl-glutaryl-CoA reductase) (P<0.05) and LDL (low-density
      lipoprotein) receptor in the liver of LP offspring were increased. Furthermore,
      LP offspring had higher LDL-cholesterol levels (P<0.05) and a trend towards
      elevated insulin. There were no differences in other lipid measurements and
      fasting glucose between groups. These observations suggest that early exposure to
      an LP diet accelerates the development and increases the progression of
      atherosclerotic lesions in young adult offspring. Future studies are needed to
      elucidate the specific mechanisms linking in utero exposure to a diet low in
      protein to the development of atherosclerosis.

PMID- 22375566
TI  - A bright future of researching AMPA receptor agonists for depression treatment.

PMID- 22375565
TI  - Home birth and hospital birth trends in Bo, Sierra Leone.
AB  - As of April 2010, all maternity care at government healthcare facilities in
      Sierra Leone is provided at no cost to patients. In late 2010, we conducted a
      community health census of 18 sections of the city of Bo (selected via randomized
      cluster sampling from 68 total sections). Among the 3421 women with a history of
      pregnancy who participated in the study, older women most often reported having a
      history of both home and hospital deliveries, while younger women showed a
      preference for hospital births. The proportion of lastborn children delivered at
      a healthcare facility increased from 71.8% of offspring 10-14 years old to 81.1%
      of those one to nine years old and 87.3% of infants born after April 2010. These
      findings suggest that the new maternal healthcare initiative has accelerated an
      existing trend toward a preference for healthcare facility births, at least in
      some urban parts of Sierra Leone.

PMID- 22375567
TI  - Evaluative thinking: a tool to inform policy development and policy impact
      evaluations.

PMID- 22375568
TI  - Effectiveness of financial incentives for longer-term smoking cessation: evidence
      of absence or absence of evidence?

PMID- 22375569
TI  - A pilot test of the Latin active hip hop intervention to increase physical
      activity among low-income Mexican-American adolescents.
AB  - PURPOSE: The primary purpose of the current study was to develop, implement, and
      evaluate a hip hop dance intervention, Latin Active, among low-income Mexican
      American adolescents. Mexican-descent adolescents tend to have disproportionate
      rates of low physical activity, overweight status, and obesity. DESIGN: A 5-week
      intervention design with pretest and post-test self-report measures. SETTING:
      Charter middle school (grades 6-9) health/science classes in a low-income
      neighborhood were the setting for the Latin Active intervention. PARTICIPANTS:
      Overall, 81 participants were recruited; 73 (n  =  41, female; n  =  32, male)
      provided active parental consent to complete pretest/post-test surveys.
      Intervention . The Latin Active program included 10 interactive 50-minute lessons
      that were delivered twice a week during science/health classes. The curriculum
      was created on the basis of Social Cognitive Theory, Critical Hip Hop Pedagogy,
      and feedback from key stakeholders. The lessons focused on increasing physical
      activity as well as neighborhood barriers. MEASURES: The self-report pretest (n 
      =  73) and post-test (n  =  56) surveys included measures for frequency of
      vigorous physical activity, self-efficacy, and neighborhood barriers. Analysis .
      Paired-sample t-test analyses were conducted to assess mean differences from
      pretest to post-test results for intervention outcomes by gender. RESULTS: The
      Latin Active program (with 77% retention at post-test) significantly increased
      vigorous physical activity and dance (p < .05) and increased self-efficacy (p <
      .05) among girls, and it decreased perception of neighborhood barriers (p < .05)
      among boys. CONCLUSION . A hip hop physical activity program, Latin Active
      demonstrated preliminary efficacy to increase girl's vigorous physical activity
      and boy's perception of neighborhood barriers to physical activity. Future
      research will need to use a randomized, controlled design and investigate the
      effect of the program on measures of body mass index.

PMID- 22375570
TI  - Improving cancer screening among women with mobility impairments: randomized
      controlled trial of a participatory workshop intervention.
AB  - PURPOSE: To assess the efficacy of an intervention to promote mammography and
      Papanicolaou (Pap) testing among women with mobility impairments overdue for
      screenings. DESIGN: Randomized controlled trial. SETTING: Urban and suburban
      Oregon. PARTICIPANTS: Women aged 35 to 64 with mobility impairments who reported
      not receiving a Pap test in the past 3 years and/or mammogram (if age >40 years)
      in the last 2 years were eligible. A total of 211 women were randomized, and 156
      completed the study (26% attrition). The majority were not employed and reported
      annual income <$10,000. INTERVENTION: The Promoting Access to Health Services
      (PATHS) program is a 90-minute, small-group, participatory workshop with 6 months
      of structured telephone support, based on the health belief model and social
      cognitive theory. MEASURES: Perceived susceptibility to breast and cervical
      cancer, perceived benefits of and self-efficacy for screening, intention to be
      screened, and self-reported receipt of mammography and Pap testing. ANALYSIS .
      Chi-square tests to examine the proportion of women obtaining screening; analysis
      of covariance to examine change in theoretical mediators. RESULTS: The
      intervention group received more Pap tests than the control group at posttest
      (intervention 61%, control 27%, n  =  71, p < .01). No significant group effect
      was observed for mammography (intervention 49%, control 42%, n  =  125, p  = 
      .45). CONCLUSION: Findings indicate that the PATHS intervention promotes Pap
      testing but not mammography among women with mobility impairments.

PMID- 22375571
TI  - Exploring and reducing stress in young restaurant workers: results of a
      randomized field trial.
AB  - PURPOSE: Young adult restaurant workers face the dual stressors of work
      adjustment and managing personal responsibilities. We assessed a new
      psychosocial/health promotion training designed to reduce these stressors in the
      context of restaurant work. DESIGN . A cluster-randomized trial of a training
      program, with surveys administered approximately 2 weeks before training and both
      6 and 12 months after training. SETTING: A national restaurant chain. SUBJECTS: A
      total of 947 restaurant workers in 28 restaurants. MEASURES: Personal stress,
      exposure to problem coworkers, and personal and job characteristics.
      INTERVENTION: Team Resilience (TR) is an interactive program for stress
      management, teamwork, and work-life balance. TR focuses on "five Cs" of
      resilience: compassion, commitment, centering, community, and confidence.
      ANALYSIS . Mixed-model (multilevel) analysis of covariances. RESULTS: Compared
      with workers in control stores, workers in TR-trained stores showed significant
      reductions over time in exposure to problem coworkers (F[2, 80.60]  =  4.48; p  =
      .01) and in personal stress (F[2, 75.28]  =  6.12; p  =  .003). CONCLUSION: The
      TR program may help young workers who face the challenges of emerging adulthood
      and work-life balance.

PMID- 22375572
TI  - Problem drinking among Mexican-Americans: the influence of nativity and
      neighborhood context?
AB  - PURPOSE: We examined the influence of nativity and community context (Hispanic
      neighborhood concentration) on two measures of problem drinking among Mexican
      Americans. DESIGN: Cross-sectional study. SETTING: Texas City Stress and Health
      Study conducted in Texas City, Texas during 2004-2006. PARTICIPANTS: A total of
      1435 Mexican-Americans aged 25 years and older. MEASURES: Binge drinking (>=6
      drinks per occasion by men and >=4 drinks per occasion by women) and scoring
      positive on the CAGE (a four-item clinical measure of problem drinking) as
      dependent variables. Key independent variables included a measure of language
      acculturation, proportion of Hispanics in the participant's neighborhood
      according to 2000 U.S. Census data, and being foreign-born compared with being
      U.S.-born. ANALYSIS: Logistic regression analysis was used to predict being a
      binge drinker and being positive on the CAGE. RESULTS . Foreign-born women were
      less likely to be binge drinkers than U.S.-born women. Nativity was not
      significant among men. Moreover women were less likely to be binge drinkers if
      they lived in heavily Hispanic neighborhoods. No such effect was found among men.
      Similar results were obtained with the CAGE. CONCLUSIONS: We found a powerful
      influence of nativity (being U.S.-born compared with foreign born) and
      neighborhood Hispanic concentration on problem drinking among women but not among
      men. It is likely that cultural norms in heavily Hispanic environments discourage
      problem drinking among women but not among men.

PMID- 22375573
TI  - Paying for prevention: associations between pay for performance and cessation
      counseling in primary care practices.
AB  - PURPOSE: To examine associations between pay for performance (P4P) and
      recommended cessation counseling among primary care practices (PCPs). DESIGN:
      Cross-sectional survey of 89 PCPs participating in a joint Robert Wood Johnson
      Foundation (RWJF)-Agency for Healthcare Research and Quality (AHRQ) health
      promotion initiative. SETTING AND PARTICIPANTS: 100% response rate from PCPs
      participating in the RWJF-AHRQ initiative. MEASURES: Survey data on cessation
      counseling, practice involvement with P4P, practice size, public reporting of
      performance, practice competition, linkages with community resources, integration
      of evidence-based guidelines, patient recommendations for cessation, and state
      specific smoking rates. ANALYSIS: Logistic regression was used to examine
      associations between practice involvement with P4P and cessation counseling
      offered by PCPs. Practice characteristics, including size and availability of
      other cessation services, were included in the analysis. RESULTS: Practices that
      were involved with P4P had greater odds of offering recommended cessation
      counseling (odds ratio [OR]  =  27.6, p < .01). Practices that linked patients to
      community resources, experienced greater competition, and were larger in size
      also provided more counseling (p < .05). Publicly reporting performance
      information and being located in states with higher smoking rates were associated
      with decreased odds of offering counseling support (p < .10). CONCLUSIONS:
      Findings suggest that P4P is associated with recommended counseling for smoking
      cessation. Study limitations include small sample size and unavailability of
      information on the magnitude of P4P incentives and program design. Further
      analysis considering these programmatic details is warranted.

PMID- 22375574
TI  - Small changes approach promotes initial and continued weight loss with a phone
      based follow-up: nine-month outcomes from ASPIRES II.
AB  - PURPOSE: To examine the impact of a small-changes weight loss program across a 3
      month intervention followed by a 6-month follow-up program. DESIGN: A one-group
      pre-post intervention study. SETTING: Medium-sized Southwestern university.
      PARTICIPANTS: Twenty-five obese adult women (mean body mass index [BMI]  =  31.8
      kg/m(2), standard deviation [SD]  =  4.9). INTERVENTION: Participants were asked
      to choose and adopt small changes in their diet and physical activity relative to
      baseline during weekly group-based meetings over 3 months. Participants then
      received bi-weekly phone calls across a 6-month follow-up period. MEASURES:
      Weight change was the primary outcome. Secondary outcomes included waist
      circumference, daily step count, and caloric intake. ANALYSES: Intention-to-treat
      analysis of change from baseline and completers-only analysis (n  =  22) for
      secondary outcomes. RESULTS: Participants achieved clinically significant weight
      loss (mean [M]  =  -3.2 kg, standard error [SE]  =  .47 kg, p < .001) across the
      initial small changes treatment program. Moreover, participants continued to lose
      weight across the 6-month phone-based follow-up program (M  =  -2.1 kg, SE  = 
      .83 kg, p < .017), totaling >5% weight loss across the 9-month program (M  =  5.3
      kg, SE  =  1.1 kg, p < .001). CONCLUSION: Using a small changes approach,
      participants achieved weight loss in an initial group-based program, which
      continued with minimal phone-based follow-up. Larger randomized studies comparing
      a small changes approach to traditional obesity treatment are warranted.

PMID- 22375575
TI  - Concordance and correlates of direct and indirect built environment measurement
      among minority women.
AB  - PURPOSE: To measure the concordance of directly and indirectly measured
      neighborhood attributes and to determine the correlates of the concordance
      between directly and indirectly measured built environment attributes. DESIGN:
      Environmental cross-sectional design. SETTING: Urban and suburban neighborhoods
      within Harris County, Houston, and Travis County, Austin, Texas. SUBJECTS:
      Community-dwelling African-American and Hispanic or Latina women. MEASURES:
      Physical activity resource accessibility, path maintenance, and pedestrian and
      bicycle facilities were measured directly and indirectly. Directly or objectively
      measured neighborhood attributes were measured by the Physical Activity Resource
      Assessment and Pedestrian Environmental Data Scan instruments. Indirectly
      measured or self-reported neighborhood attributes were measured by the
      International Physical Activity Prevalence Study environmental survey module.
      ANALYSIS: Logistic regression was used to measure the concordance between
      directly and indirectly measured neighborhood attributes with ethnicity as a
      covariate. Residual values were calculated to determine the strength and
      direction of concordance. RESULTS: Participants' (N  =  409) average body mass
      index (BMI) was classified as obese (MBMI  =  34.5 kg/m(2), SD  =  7.9), and the
      mean body fat percentage was 42.8% (SD  =  7.1). The correlates BMI, body fat
      percentage, physical activity, and ethnicity were not significantly associated
      with any built environment attribute or concordance value, and none of our models
      significantly predicted indirectly measured built environment attributes.
      CONCLUSION: Being less familiar with certain built environment attributes may not
      be associated with weight status or physical activity levels among African
      American and Hispanic or Latina women.

PMID- 22375576
TI  - Medical cost savings for participants and nonparticipants in health risk
      assessments, lifestyle management, disease management, depression management, and
      nurseline in a large financial services corporation.
AB  - PURPOSE: To compare changes in medical costs between participants and
      nonparticipants in five different health and productivity management (HPM)
      programs. DESIGN: Quasi-experimental pre/post intervention study. SETTING: A
      large financial services corporation. SUBJECTS: A cohort population of employees
      enrolled in medical plans (n  =  49,723) [corrected]. INTERVENTION: A
      comprehensive HPM program, which addressed health risks, acute and chronic
      conditions, and psychosocial disorders from 2005 to 2007. Incentives were used to
      encourage health risk assessment participation in years 2 and 3. MEASURES:
      Program participation and medical claims data were collected for members at the
      end of each program year to assess the change in total costs from the baseline
      period. Analysis . Multivariate analyses for participation categories were
      conducted comparing baseline versus program year cost differences, controlling
      for demographics. RESULTS: All participation categories yielded a lower cost
      increase compared to nonparticipation and a positive return on investment (ROI)
      for years 2 and 3, resulting in a 2.45?1 ROI for the combined program years.
      CONCLUSION: Medical cost savings exceeded program costs in a wide variety of
      health and productivity management programs by the second year.

PMID- 22375577
TI  - Translation from research to practice: community dissemination of a telephone
      delivered physical activity and dietary behavior change intervention.
AB  - PURPOSE: To describe the process of translating an evidence-based, telephone
      delivered physical activity and dietary behavior change intervention from
      research into practice. DESIGN: Descriptive case study. SETTING/SUBJECTS:
      Nongovernment, primary medical care-based community health organization.
      INTERVENTION: Telephone-delivered intervention targeting physical activity and
      diet in primary medical care patients. MEASURES/ANALYSIS: Systematic
      documentation of process outcomes related to intervention adoption and
      adaptation. RESULTS: Research-community partnerships were critical in
      facilitating translation, including (1) an initial competitive advantage within a
      State Health Department-funded preventive health initiative; (2) advocacy to
      ensure the adoption of the intervention, (3) subsequent support for the
      adaptation of program elements to ensure fit of the program with the community
      organization's objectives and capacities, while maintaining feasible elements of
      fidelity with the original evidence-based program; (4) the integration of program
      management and evaluation systems within the community organization; and (5)
      ongoing support for staff members responsible for program delivery and
      evaluation. Preliminary process evaluation of the Optimal Health Program supports
      the acceptability and feasibility of the program within community practice.
      CONCLUSIONS: INTERVENTION characteristics central to adoption can be influenced
      by research-community partnerships. It is likely that evidence-based
      interventions will need to be adapted for delivery within the real world.
      Researchers should endeavor to provide training and support to ensure, as much as
      possible, fidelity with the original program, and that the relevant adaptations
      are evidence based.

PMID- 22375579
TI  - Effects of a culturally tailored physical activity promotion program on selected
      self-regulation skills and attitudes in adolescents of an underserved,
      multiethnic milieu.
AB  - PURPOSE: To implement a culturally tailored physical activity (PA) promotion
      program (FunAction) and to assess its impact on five self-regulation skills and
      attitudes in adolescents. Design . The design and implementation of the FunAction
      program were informed by social marketing principles. The study used a quasi
      experimental approach to assess the impact of the program on specific outcome
      variables. SETTING: A multiethnic, underserved middle school in Montreal, Quebec,
      Canada. SUBJECTS: The intervention group was made up of grade 8 students (n  = 
      165) and the control group was made up of grade 7 students (n  =  137).
      INTERVENTION: During the 16-week intervention, adolescents were able to choose
      from a variety of 45-minute cardiovascular PAs offered daily during their school
      lunch period. Adolescents participated in the activities on a voluntary basis.
      MEASURES: A self-report questionnaire was administered preintervention and
      postintervention to measure adolescents' scores on the following self-regulation
      skills and attitudes: self-control, self-esteem, attention/concentration, social
      competence, and interethnic relationships. ANALYSIS: Three-way repeated measures
      analyses of variance and correlational analyses were used. Results . A
      significant improvement was observed only in attention/concentration. Girls'
      attention/concentration scores improved significantly in the intervention group
      compared to the control group (F(1,127)  =  16.26, p < .001). The improvement in
      attention/concentration scores for boys in the intervention group was correlated
      with their frequency of participation in the program PAs (r  =  .24, p  =  .008).
      CONCLUSION: Using social marketing principles can help encourage adolescents from
      underserved, multiethnic milieus to participate in PA during their school lunch
      hour. Furthermore, voluntary participation in a culturally tailored PA program
      can improve youths' attention/concentration.

PMID- 22375582
TI  - Erosion of our moral compass, social trust, and the fiscal strength of the United
      States: income inequality, tax policy, and well-being.

PMID- 22375580
TI  - Mediating effects of group cohesion on physical activity and diet in women of
      color: health is power.
AB  - PURPOSE: To determine the effects and mediating factors of a physical activity
      (PA) or vegetable and fruit (VF) group cohesion intervention. DESIGN:
      Longitudinal design. SETTING: Harris County and Travis County, Texas.
      PARTICIPANTS: Community-dwelling African-American and Hispanic or Latina women.
      INTERVENTION: Three hundred ten women were randomized to a PA (n  =  204) or VF
      (n  =  106) intervention group. Women met in groups six times over the course of
      6 months and were exposed to a group cohesion intervention to promote walking or
      to increase VF consumption. MEASURES: Women completed the International PA
      Questionnaire, National Cancer Institute VF and fat screeners, PA Group
      Environment Questionnaire, and 7-day accelerometer protocol at baseline and post
      intervention. ANALYSES: The direct and mediated effects of the intervention on
      outcomes were evaluated using a mediational chain model, controlling for baseline
      values and covariates using path analysis. RESULTS: Women were middle aged (mean 
      =  44.4 years) and overweight or obese (mean body mass index  =  34.0 kg/m(2)).
      PA increased and fat consumption decreased for both groups, whereas VF
      consumption increased for women in VF group only (all p < .05). Increased task
      cohesion led to hypothesized increases in psychosocial factors in the PA group
      but not to behavioral changes. CONCLUSIONS: Group cohesion interventions may have
      psychological and physical health benefits for African-American and Hispanic or
      Latina women, but refinement of measures and intervention delivery is needed to
      determine whether hypothesized mediational pathways are valid.

PMID- 22375583
TI  - Meta-evaluation of worksite health promotion economic return studies: 2012
      update.

PMID- 22375585
TI  - Very late prostate cancer local recurrence 23 years after radical prostatectomy.
AB  - Recurrence after radical prostatectomy occurs most frequently during the first 5
      years after surgery. Later recurrences have, however, been described. This report
      describes a case with local recurrence 23 years after radical prostatectomy.

PMID- 22375586
TI  - Biodegradation of nicosulfuron by the bacterium Serratia marcescens N80.
AB  - By enrichment culturing of the sludge collected from the industrial wastewater
      treatment pond, we isolated a highly efficient nicosulfuron degrading bacterium
      Serratia marcescens N80. In liquid medium, Serratia marcescens N80 grows using
      nicosulfuron as the sole nitrogen source, and the optimal temperature, pH values,
      and inoculation for degradation are 30-35 degrees C, 6.0-7.0, and 3.0% (v/v),
      respectively. With the initial concentration of 10 mg L-1, the degradation rate
      is 93.6% in 96 hours; as the initial concentrations are higher than 10 mg L-1,
      the biodegradation rates decrease as the nicosulfuron concentrations increase;
      when the concentration is 400 mg L-1, the degradation rate is only 53.1%.
      Degradation follows the pesticide degradation kinetic equation at concentrations
      between 5 mg L-1 and 50 mg L-1. Identification of the metabolites by the liquid
      chromatography/mass spectrometry (LC/MS) indicates that the degradation of
      nicosulfuron is achieved by breaking the sulfonylurea bridge. The strain N80 also
      degraded some other sulfonylurea herbicides, including ethametsulfuron,
      tribenuron-methyl, metsulfuron-methyl, chlorimuron-ethyl,and rimsulfuron.

PMID- 22375587
TI  - Effects of sewage sludge amendments on pesticide sorption and leaching through
      undisturbed Mediterranean soils.
AB  - The Gharb region in Morocco is an important agricultural zone where soils receive
      pesticide treatments and organic amendments to increase yields. The groundwater
      aquifer in the Gharb region is relatively shallow and thus vulnerable. The
      objective of this work was to study the influence of organic amendments on
      diuron, cyhalofop-butyl and procymidone leaching through undisturbed soil
      columns. Two soils were sampled from the Gharb region, a Dehs (sandy soil) and a
      R'mel (loamy clay soil). Following elution (124.5 mm), the amount of pesticide
      residues in the leachates of the sandy soil (0.06-0.21 %) was lower than in those
      of the loamy clay soil (0.20-0.36 %), which was probably due to preferential flow
      through the loamy clay soil. The amount of procymidone leached through the
      amended soil columns was greater than the control for the sandy soil only. The
      organic amendments did not significantly influence diuron and cyhalofop-butyl
      leaching in either of the soils. The application of organic amendments affected
      the amounts of dissolved organic matter (DOM) eluted and thus pesticide leaching
      as a function of soil-type. Nevertheless, in some case, the formation of
      pesticide-DOM complexes appeared to promote pesticide leaching, thus increasing
      groundwater contamination risks.

PMID- 22375588
TI  - Sorption-desorption behavior of metsulfuron-methyl and sulfosulfuron in soils.
AB  - Sorption of metsulfuron-methyl and sulfosulfuron were studied in five Indian
      soils using batch sorption method. Freundlich adsorption equation described the
      sorption of herbicides with K(f) (adsorption coefficient) values ranging between
      0.21 and 1.88 (metsulfuron-methyl) and 0.37 and 1.17 (sulfosulfuron). Adsorption
      isotherms were L-type suggesting that the herbicides sorption decreased with
      increase in the initial concentration of the herbicide in the solution. The K(f)
      for metsulfuron-methyl showed good positive correlation with silt content
      (significant at p = 0.01) and strong negative correlation with the soil pH
      (significant at p = 0.05) while sorption of sulfosulfuron did not correlate with
      any of the soil parameter. Desorption of herbicides was concentration dependent
      and, in general, sulfosulfuron showed higher desorption than the metsulfuron
      methyl. The study indicates that these herbicides are poorly sorbed in the Indian
      soil types and there may be a possibility of their leaching to lower soil
      profiles.

PMID- 22375589
TI  - In vitro activity of antimicrobial agents against Pseudomonas tolaasii, pathogen
      of cultivated button mushroom.
AB  - In vitro antibacterial activity tests of seven biofungicides (Ekstrasol,
      Bisolbisan, Bisolbifit, Serenade, Sonata, Timorex, F-Stop) and two disinfectants
      (colloidal silver alone and in combination with hydrogen peroxide) against the
      Pseudomonas tolaasii strain (NS3B6) were carried out by the disc-diffusion, broth
      microdilution and broth macrodilution method. Biofungicides tested in this study
      did not exhibit any antimicrobial activity in neither one of the methods used.
      Disc diffusion method revealed high sensitivity of the tested P. tolaasii strain
      to Ecocute based on colloidal silver and hydrogen peroxide. Both microdilution
      and macrodilution methods identified the same MICs and MBCs of Ecocute (0.19
      mg/L) for P. tolaasii strain. MICs and MBCs values of silver alone were much
      higher (10 mg/L) compared to silver in combination with hydrogen peroxide.

PMID- 22375590
TI  - Histopathological alterations in gill, liver and kidney of common carp exposed to
      chlorpyrifos.
AB  - Histopathological alterations in gill, liver and kidney of common carp, Cyprinus
      carpio, intoxicated with sub-lethal concentrations of chlorpyrifos (O,O,-diethyl
      O-3,5,6-trichloro-2-pyridyl phosphorothioate) pesticide (1 and 100 MUg/L) for a
      period of 14 days were analyzed under light microscope. Gill exhibited
      hyperplasia and hypertrophy of gill epithelium, blood congestion, dilation of
      marginal channel, epithelial lifting, lamellar fusion, lamellar disorganization,
      lamellar aneurysm, rupture of the lamellar epithelium, rupture of pillar cells
      and necrosis. Alterations in hepatocytes were more pronounced, including nuclear
      and cellular hypertrophy, cellular atrophy, irregular contour of cells and
      nucleus, cytoplasmic vacuolation, cytoplasmic and nuclear degeneration, cellular
      rupture, pyknotic nucleus, necrosis and melanomacrophages aggregations.
      Histopathological lesions in kidney were cellular and nuclear hypertrophy,
      narrowing of tubular lumen, cytoplasmic vacuolation, hyaline droplet
      degeneration, nuclear degeneration, occlusion of tubular lumen, tubular
      regeneration, dilation of glomerular capillaries, degeneration of glomerulus and
      hemorrhage in Bowman's space. The most significant conclusion drawn from this
      study was that with the increased concentration and duration the toxicosis of
      chlorpyrifos would be enhanced as shown through the analysis of mean assessment
      value (MAV) and degree of tissue changes (DTC) also.

PMID- 22375591
TI  - Effects of parabens on apoptosis induced by serum-free medium.
AB  - Alkyl esters of p-hydroxybenzoic acids (parabens), an endocrine disrupter, are
      used as preservatives in cosmetics and foods. In this study, to understand the
      relationship between parabens and differentiation in infants, the effects of
      parabens on apoptosis induced by serum deprivation in PC12 cells were
      investigated. In addition, apoptosis-related factors were assayed. As results, a
      tendency toward enhancement of apoptosis was observed in the cells cultured in
      the serum-free medium with methylparaben, and this tendency was suggested to be
      related to the contents of BAD, a pro-apoptotic protein. Butylparaben did not
      show any tendency to enhance apoptosis.

PMID- 22375592
TI  - Effect of vermicomposting on calcium, sulphur and some heavy metal content of
      different biodegradable organic wastes under liming and microbial inoculation.
AB  - A study was conducted to evaluate the changes in total calcium and sulphur and
      some heavy metal (Zn, Cu, and Pb) concentration of different organic wastes
      affected by liming and microorganism inoculation. Vermicomposting was an
      effective technology for disposal of organic substrates like municipal solid
      wastes (MSW), possessing comparatively higher concentration of heavy metals. The
      addition of lime in initial organic substrates significantly (P <= 0.05)
      increased total calcium and total sulphur content of vermicomposts. Inoculation
      of microorganisms significantly (P <= 0.05) reduced the heavy metal content of
      final products as compared to control. Fungal strains were comparatively more
      effective in detoxification of heavy metals than B. polymyxa.

PMID- 22375593
TI  - Detection of Listeria monocytogenes in ready-to-eat food by Step One real-time
      polymerase chain reaction.
AB  - The aim of this study was to follow contamination of ready-to-eat food with
      Listeria monocytogenes by using the Step One real time polymerase chain reaction
      (PCR). We used the PrepSEQ Rapid Spin Sample Preparation Kit for isolation of DNA
      and MicroSEQ(r) Listeria monocytogenes Detection Kit for the real-time PCR
      performance. In 30 samples of ready-to-eat milk and meat products without
      incubation we detected strains of Listeria monocytogenes in five samples (swabs).
      Internal positive control (IPC) was positive in all samples. Our results
      indicated that the real-time PCR assay developed in this study could sensitively
      detect Listeria monocytogenes in ready-to-eat food without incubation.

PMID- 22375594
TI  - Development of controlled release formulations of imidacloprid employing novel
      nano-ranged amphiphilic polymers.
AB  - Amphiphilic copolymers, synthesized from poly (ethylene glycols) and various
      aliphatic diacids, which self assemble into nano-micellar aggregates in aqueous
      media, were used to develop controlled release (CR) formulations of imidacloprid
      [1-(6 chloro-3-pyridinyl methyl)-N-nitro imidazolidin-2-ylideneamine] using
      encapsulation technique. High solubilisation power and low critical micelle
      concentration (CMC) of these amphiphilic polymers may increase the efficacy of
      formulations. Formulations were characterised by Infrared (IR) spectroscopy,
      Dynamic Light Scattering (DLS) and Transmission Electron Microscope (TEM).
      Encapsulation efficiency, loading capacity and stability after accelerated
      storage test of the developed formulations were checked. The kinetics of
      imidacloprid release in water from the different formulations was studied.
      Release from the commercial formulation was faster than the CR formulations. The
      diffusion exponent (n value) of imidacloprid, in water ranged from 0.22 to 0.37
      in the tested formulations. While the time taken for release of 50 % of
      imidacloprid ranged from 2.32 to 9.31 days for the CR formulations. The developed
      CR formulations can be used for efficient pest management in different crops.

PMID- 22375595
TI  - Residue and bio-efficacy evaluation of controlled release formulations of
      imidacloprid against pests in soybean (Glycine max).
AB  - Controlled release (CR) formulations of imidacloprid (1-(6 chloro-3-pyridinyl
      methyl)-N- nitro imidazolidin-2- ylideneamine) were prepared using novel
      amphiphilic polymers synthesized from polyethylene glycol and aliphatic diacids
      employing encapsulation technique. The bioefficacy of the prepared CR
      formulations was evaluated against major pests of soybean, namely stem fly,
      Melanagromyza sojae Zehntmer and white fly, Bemisia tabaci Gennadius along with a
      commercial formulation at the experimental farm of Indian Agricultural Research
      Institute (IARI), New Delhi during kharif 2009 and 2010. Most of the CR
      formulations of imidacloprid gave significantly better control of the pests
      compare to its commercial formulations, however the CR formulations, Poly [poly
      (oxyethylene-1000)-oxy suberoyl] amphiphilic polymer based formulation performed
      better over others for controlling of both stem fly incidence and Yellow Mosaic
      Virus (YMV) infestation transmitted by white fly. Some of the developed CR
      formulations recorded higher yield over commercial formulation and control.
      Nodulation pattern of soybean was not affected due to treatment of CR and
      commercial formulations of imidacloprid. Also the residues of imidacloprid in
      seed and soil at harvest were not detectable for both CR and commercial
      formulations.

PMID- 22375596
TI  - Large area extreme-UV lithography of graphene oxide via spatially resolved
      photoreduction.
AB  - The ability to pattern graphene over large areas with nanometer resolution is the
      current request for nanodevice fabrication at the industrial scale. Existing
      methods do not match high throughput with nanometer resolution. We propose a high
      throughput resistless extreme-UV (EUV) photolithographic approach operating with
      sub-micrometer resolution on large area (~10 mm(2)) graphene oxide (GO) films via
      spatially resolved photoreduction. The efficiency of EUV photoreduction is tested
      with 46.9 nm coherent light produced by a table top capillary discharge plasma
      source. Irradiated samples are studied by X-ray photoemission spectroscopy (XPS)
      and micro-Raman Spectroscopy (MURS). XPS data show that 200 mJ/cm(2) EUV dose
      produces, onto pristine GO, a 6% increase of sp(2) carbon bonds and a 20%
      decrease of C-O bonds. MURS data demonstrate a photoreduction efficiency 2 orders
      of magnitude higher than the one reported in the literature for UV-assisted
      photoreduction. GO patterning is obtained modulating the EUV dose with a Lloyd's
      interferometer. The lithographic features consist of GO stripes with modulated
      reduction degree. Such modulation is investigated and demonstrated by MURS on
      patterns with 2 MUm periodicity.

PMID- 22375597
TI  - Metabolite profiling of maize kernels--genetic modification versus environmental
      influence.
AB  - A metabolite profiling approach based on gas chromatography-mass spectrometry (GC
      MS) was applied to investigate the metabolite profiles of genetically modified
      (GM) Bt-maize (DKC78-15B, TXP 138F) and Roundup Ready-maize (DKC78-35R). For the
      comparative investigation of the impact of genetic modification versus
      environmental influence on the metabolite profiles, GM maize was grown together
      with the non-GM near-isogenic comparators under different environmental
      conditions, including several growing locations and seasons in Germany and South
      Africa. Analyses of variance (ANOVA) revealed significant differences between GM
      and non-GM maize grown in Germany and South Africa. For the factor genotype, 4
      and 3%, respectively, of the total number of peaks detected by GC-MS showed
      statistically significant differences (p < 0.01) in peak heights as compared to
      the respective isogenic lines. However, ANOVA for the factor environment (growing
      location, season) revealed higher numbers of significant differences (p < 0.01)
      between the GM and the non-GM maize grown in Germany (42%) and South Africa
      (10%), respectively. This indicates that the majority of differences observed are
      related to natural variability rather than to the genetic modifications. In
      addition, multivariate data assessment by means of principal component analysis
      revealed that environmental factors, that is, growing locations and seasons, were
      dominant parameters driving the variability of the maize metabolite profiles.

PMID- 22375598
TI  - Time-resolved Fourier transform emission spectroscopy of He/CH4 in a positive
      column discharge.
AB  - Time-resolved Fourier transform infrared emission spectroscopy was applied to the
      study of a pulsed discharge in a He/CH(4) mixture. The dynamics of the formation
      and decay of acetylene nu(3) (3289 cm(-1)), methane nu(3) (3019 cm(-1)) and nu(1)
      (2917 cm(-1)), the CH radical electronic ground state X(2)Pi(r) (2309-2953 cm(
      1)), C(2) Bernath electronic transition B(1)Delta(g)-A(1)Pi(u) (3337-3606 cm(
      1)), molecular hydrogen emission transitions 5g-4f and 2p-2s, atomic hydrogen,
      and atomic helium were monitored in the 1800-4000 cm(-1) region. The time profile
      of the rotational and vibrational temperature of the CH radical was obtained for
      a 30 MUs time interval during and after the discharge pulse. A kinetic model was
      used for the study of the chemical dynamics of the formation and decay of the
      individual fragments. The results from the model were compared to the
      experimental emission spectra.

PMID- 22375600
TI  - Molecular packing and solar cell performance in blends of polymers with a
      bisadduct fullerene.
AB  - We compare the solar cell performance of several polymers with the conventional
      electron acceptor phenyl-C61-butyric acid methyl ester (PCBM) to fullerenes with
      one to three indene adducts. We find that the multiadduct fullerenes with lower
      electron affinity improve the efficiency of the solar cells only when they do not
      intercalate between the polymer side chains. When they intercalate between the
      side chains, the multiadduct fullerenes substantially reduce solar cell
      photocurrent. We use X-ray diffraction to determine how the fullerenes are
      arranged within crystals of poly-(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2
      b]thiophene) (PBTTT) and suggest that poor electron transport in the molecularly
      mixed domains may account for the reduced solar cell performance of blends with
      fullerene intercalation.

PMID- 22375599
TI  - Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate
      in isolated rat's lungs.
AB  - BACKGROUND: Phorbol myristate acetate (PMA) is a strong neutrophil activator and
      has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound
      of B complex. It exerts protective effects on the ALI caused by various
      challenges. The purpose was to evaluate the protective effects of niacinamide
      (NAC) on the PMA-induced ALI and associated changes. METHODS: The rat's lungs
      were isolated in situ and perfused with constant flow. A total of 60 isolated
      lungs were randomized into 6 groups to received Vehicle (DMSO 100 MUg/g), PMA 4
      MUg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight).
      There were 10 isolated lungs in each group. We measured the lung weight and
      parameters related to ALI. The pulmonary arterial pressure and capillary
      filtration coefficient (Kfc) were determined in isolated lungs. ATP
      (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase]
      contents in lung tissues were detected. Real-time PCR was employed to display the
      expression of inducible and endothelial NO synthases (iNOS and eNOS). The
      neutrophil-derived mediators in lung perfusate were determined. RESULTS: PMA
      caused increases in lung weight parameters. This agent produced pulmonary
      hypertension and increased microvascular permeability. It resulted in decrease in
      ATP and increase in PARP. The expression of iNOS and eNOS was upregulated
      following PMA. PMA increased the neutrophil-derived mediators. Pathological
      examination revealed lung edema and hemorrhage with inflammatory cell
      infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive
      cells in macrophages and endothelial cells. These pathophysiological and
      biochemical changes were diminished by NAC treatment. The NAC effects were dose
      dependent. CONCLUSIONS: Our results suggest that neutrophil activation and
      release of neutrophil-derived mediators by PMA cause ALI and associated changes.
      NO production through the iNOS-producing cells plays a detrimental role in the
      PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative
      effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory
      cascade leading to pulmonary injury. This B complex compound may be applied for
      clinical usage and therapeutic regimen.

PMID- 22375603
TI  - Further investigation of the validity and reliability of the photographic figure
      rating scale for body image assessment.
AB  - Previous studies have not fully investigated the psychometric properties of the
      Photographic Figure Rating Scale (PFRS). In 2 studies, we report on the test
      retest reliability and convergent validity of ratings derived from the PFRS. In
      Study 1, 322 female university students in Britain provided self-ratings on the
      PFRS and objectively measured body mass index (BMI); a subsample of 132 women
      also completed the task after 5 weeks. In Study 2, 243 women from the community
      in Austria completed the PFRS along with a battery of other body image scales.
      Results of Study 1 showed that ratings on the PFRS had good test-retest
      reliability (all rs > .87) and good convergent validity in relation to BMI.
      Results of Study 2 showed that PFRS-derived body dissatisfaction scores were
      significantly correlated with a range of body image variables. These results
      provide evidence for the convergent validity and good test-retest reliability of
      the PFRS.

PMID- 22375604
TI  - Prophylaxis for ribavirin-related anemia using eicosapentaenoic acid in chronic
      hepatitis C patients.
AB  - BACKGROUND: Ribavirin-related anemia is a serious side-effect of the pegylated
      interferon and ribavirin therapy used for hepatitis C, and may be cause for a
      reduction in ribavirin dose or even cessation of treatment. The aim of this study
      was to evaluate the prophylactic effects of oral eicosapentaenoic acid (EPA)
      supplementation on ribavirin-induced hemolytic anemia in pediatric and young
      adult patients. METHODS: Twelve chronic hepatitis C patients ranging in age from
      3 to 21 years (mean, 13.9 +/- 5.1 years) who received pegylated interferon alpha
      2b and ribavirin combination therapy were randomized to either the control group
      (n = 6) or EPA group (n = 6). Blood samples were collected before, and at 4, 8,
      and 16 weeks after treatment to measure clinical laboratory parameters. RESULTS:
      The reduction in hemoglobin levels of the EPA group was significantly ameliorated
      at 8 and 16 weeks when compared to the control group (P < 0.05). There was no
      significant difference in plasma ribavirin concentrations between the two groups
      during the treatment. However, one patient in the control group had a reduction
      in ribavirin dose. CONCLUSION: EPA supplementation prevented ribavirin-induced
      hemolytic anemia during combination therapy with pegylated interferon alpha-2b
      and ribavirin in pediatric and young adult patients.

PMID- 22375605
TI  - Involvement of estrogen receptors in prostatic diseases.
AB  - Accumulating evidence shows that estrogens participate in the pathogenesis and
      development of benign prostatic hyperplasia and prostate cancer by activating
      estrogen receptor alpha. In contrast, estrogen receptor beta is involved in the
      differentiation and maturation of prostatic epithelial cells, and thus possesses
      antitumor effects in prostate cancer. However, the natural ligands of estrogen
      receptor beta are not fully understood, and its mode of action according to its
      ligands and the binding sites located in the promoter regions of downstream genes
      remains to be elucidated. Here, we review recent experimental investigations of
      estrogen receptors and their urological relevance. Estrogen receptor-mediated
      signaling in the prostate is essential together with the androgen receptor
      mediated pathway, providing a new therapeutic target for prostatic diseases.

PMID- 22375607
TI  - A common tool for rare diseases.

PMID- 22375608
TI  - Dissolution of cerium(IV)-lanthanide(III) oxides: comparative effect of chemical
      composition, temperature, and acidity.
AB  - The dissolution of Ce(1-x)Ln(x)O(2-x/2) solid solutions was undertaken in various
      acid media in order to evaluate the effects of several physicochemical parameters
      such as chemical composition, temperature, and acidity on the reaction kinetics.
      The normalized dissolution rates (R(L,0)) were found to be strongly modified by
      the trivalent lanthanide incorporation rate, due to the presence of oxygen
      vacancies decreasing the samples cohesion. Conversely, the nature of the
      trivalent cation considered only weakly impacted the R(L,0) values. The
      dependence of the normalized dissolution rates on the temperature then appeared
      to be of the same order of magnitude than that of chemical composition. Moreover,
      it allowed determining the corresponding activation energy (E(A) ~ 60-85 kJ.mol(
      1)) which accounts for a dissolution driven by surface-controlled reactions. A
      similar conclusion was made regarding the acidity of the solution: the partial
      order related to (H(3)O(+)) reaching about 0.7. Finally, the prevailing effect of
      the incorporation of aliovalent cations in the fluorite-type CeO(2) matrix on the
      dissolution kinetics precluded the observation of slight effects such as those
      linked to the complexing agents or to the crystal structure of the samples.

PMID- 22375609
TI  - Assessment of the scale, coverage and outcomes of the Avahan HIV prevention
      program for female sex workers in Tamil Nadu, India: is there evidence of an
      effect?
AB  - BACKGROUND: Avahan, the India AIDS Initiative, a large-scale HIV prevention
      program, using peer-mediated approaches and STI services, was implemented for
      high-risk groups for HIV in six states in India. This paper describes the
      assessment of the program among female sex workers (FSWs) in the southern state
      of Tamil Nadu. METHODS: An analytical framework based on the Avahan impact
      evaluation design was used. Routine program monitoring data, two rounds of cross
      sectional biological and behavioural surveys among FSWs in 2006 (Round 1) and
      2009 (Round 2) and quality assessments of clinical services for sexually
      transmitted infections (STIs) were used to assess trends in coverage, condom use
      and prevalence of STIs, HIV and their association with program exposure. Logistic
      regression analysis was used to examine trends in intermediate outcomes and their
      associations with intervention exposure. RESULTS: The Avahan program in Tamil
      Nadu was scaled up and achieved monthly reported coverage of 79% within four
      years of implementation. The cross-sectional survey data showed an increasing
      proportion of FSWs being reached by Avahan, 54% in Round 1 and 86% in Round 2
      [AOR=4.7;p=0.001]. Quality assessments of STI clinical services showed consistent
      improvement in quality scores (3.0 in 2005 to 4.5 in 2008). Condom distribution
      by the program rose to cover all estimated commercial sex acts. Reported
      consistent condom use increased between Round 1 and Round 2 with occasional (72%
      to 93%; AOR=5.5; p=0.001) and regular clients (68% to 89%; AOR=4.3; p=0.001)
      while reactive syphilis serology declined significantly (9.7% to 2.2% AOR=0.2;
      p=0.001). HIV prevalence remained stable at 6.1% between rounds. There was a
      strong association between Avahan exposure and consistent condom use with
      commercial clients; however no association was seen with declines in STIs.
      CONCLUSIONS: The Avahan program in Tamil Nadu achieved high coverage of FSWs,
      resulting in outcomes of improved condom use, declining syphilis and stabilizing
      HIV prevalence. These expected outcomes following the program logic model and
      declining HIV prevalence among general population groups suggest potential impact
      of high risk group interventions on HIV epidemic in Tamil Nadu.

PMID- 22375610
TI  - Auditing Nicaragua's anti-corruption struggle, 1998 to 2009.
AB  - BACKGROUND: Four social audits in 1998, 2003, 2006 and 2009 identified actions
      that Nicaragua could take to reduce corruption and public perception in primary
      health care and other key services. METHODS: In a 71-cluster sample, weighted
      according to the 1995 census and stratified by geographic region and settlement
      type, we audited the same five public services: health centres and health posts,
      public primary schools, municipal government, transit police and the courts. Some
      6,000 households answered questions about perception and personal experience of
      unofficial and involuntary payments, payments without obtaining receipts or to
      the wrong person, and payments "to facilitate" services in municipal offices or
      courts. Additional questions covered complaints about corruption and confidence
      in the country's anti-corruption struggle. Logistic regression analyses helped
      clarify local variations and explanatory variables. Feedback to participants and
      the services at both national and local levels followed each social audit.
      RESULTS: Users' experience of corruption in health services, education and
      municipal government decreased. The wider population's perception of corruption
      in these sectors decreased also, but not as quickly. Progress among traffic
      police faltered between 2006 and 2009 and public perception of police corruption
      ticked upwards in parallel with drivers' experience. Users' experience of
      corruption in the courts worsened over the study period--with the possible
      exception of Managua between 2006 and 2009--but public perception of judicial
      corruption, after peaking in 2003, declined from then on. Confidence in the anti
      corruption struggle grew from 50% to 60% between 2003 and 2009. Never more than
      8% of respondents registered complaints about corruption.Factors associated with
      public perception of corruption were: personal experience of corruption, quality
      of the service itself, and the perception that municipal government takes
      community opinion into account and keeps people informed about how it uses public
      funds. CONCLUSIONS: Lowering citizens' perception of corruption in public
      services depends on reducing their experience of it, on improving service quality
      and access and--perhaps most importantly--on making citizens feel they are well
      informed participants in the work of government.

PMID- 22375612
TI  - A randomized non-inferiority study comparing the addition of exenatide twice
      daily to sitagliptin or switching from sitagliptin to exenatide twice daily in
      patients with type 2 diabetes experiencing inadequate glycaemic control on
      metformin and sitagliptin.
AB  - AIMS: To test the hypothesis that glycaemic control achieved when switching
      sitagliptin to exenatide twice daily plus metformin is non-inferior to adding
      exenatide twice daily to sitagliptin and metformin. METHODS: Patients with Type 2
      diabetes inadequately controlled with sitagliptin plus metformin were randomly
      assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and
      metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and
      metformin (ADD, n = 128). RESULTS: Non-inferiority (0.4% margin) of SWITCH to ADD
      treatment, measured by change in HbA(1c) from baseline to week 20, was not shown
      {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)]
      [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares
      mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%]
      [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0
      (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group
      (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the
      SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater
      fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored
      blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group,
      by week 20. Patients in both groups experienced a lower incidence of nausea and
      vomiting compared with previous exenatide studies. CONCLUSIONS: Non-inferiority
      of SWITCH to ADD treatment was not supported by the results of this study. In
      patients with Type 2 diabetes inadequately controlled with sitagliptin plus
      metformin, adding exenatide provided better glycaemic control than switching to
      exenatide. These results are consistent with the clinical approach that adding is
      better than switching to another oral anti-hyperglycaemic medication.

PMID- 22375613
TI  - Pregnancy outcomes and the effect of metformin treatment in women with polycystic
      ovary syndrome: an overview.
AB  - This article is a review of the literature assessing pregnancy outcomes and the
      effect of metformin treatment among women with polycystic ovary syndrome (PCOS).
      A review of research published in English was undertaken using PubMed and MEDLINE
      databases. The weight of the available evidence suggests that pregnant women with
      PCOS are at an increased risk of developing gestational diabetes, hypertensive
      disorders of pregnancy, preterm birth and early pregnancy loss. Obesity is a
      contributory factor for the increased risk of gestational diabetes in this group
      of women and is estimated to affect 5-40% of pregnant women with PCOS. The
      prevalence of other obstetric complications is estimated at 10-30% for
      gestational hypertension, 8-15% for pre-eclampsia and 6-15% for preterm birth.
      The association between PCOS and early pregnancy loss may not be direct, wherein
      the presence of PCOS-associated hyperinsulinemia, leading to hyperandrogenemia,
      has been implicated in the pathophysiology of early pregnancy loss. Apart from
      the role of metformin in improving the metabolic consequences accompanying PCOS,
      it has been shown to improve pregnancy rates in women with PCOS who are resistant
      to clomiphene citrate. In conclusion, pregnancy in women with PCOS is associated
      with adverse obstetric outcomes (multiple adverse obstetric risk). Whether
      metformin should be administered throughout pregnancy still remains
      controversial. Further prospective studies that foster a larger number of
      participants and adjust for all potentially confounding factors are needed.

PMID- 22375614
TI  - Magnetic resonance imaging for diagnosis of acute pulmonary embolism: not yet a
      suitable alternative to CT-PA.

PMID- 22375615
TI  - General practitioners' experiences with sickness certification: a comparison of
      survey data from Sweden and Norway.
AB  - BACKGROUND: In most countries with sickness insurance systems, general
      practitioners (GPs) play a key role in the sickness-absence process. Previous
      studies have indicated that GPs experience several tasks and situations related
      to sickness certification consultations as problematic. The fact that the
      organization of primary health care and social insurance systems differ between
      countries may influence both GPs' experiences and certification. The aim of the
      present study was to gain more knowledge of GPs' experiences of sickness
      certification, by comparing data from Sweden and Norway, regarding frequencies
      and aspects of sickness certification found to be problematic. METHODS:
      Statistical analyses of cross-sectional survey data of sickness certification by
      GPs in Sweden and Norway. In Sweden, all GPs were included, with 3949 (60.6%)
      responding. In Norway, a representative sample of GPs was included, with 221
      (66.5%) responding. RESULTS: Most GPs reported having consultations involving
      sickness certification at least once a week; 95% of the GPs in Sweden and 99% of
      the GPs in Norway. A majority found such tasks problematic; 60% of the GPs in
      Sweden and 53% in Norway. In a logistic regression, having a higher frequency of
      sickness certification consultations was associated with a higher risk of
      experiencing them as problematic, in both countries. A higher rate of GPs in
      Sweden than in Norway reported meeting patients wanting a sickness certification
      without a medical reason. GPs in Sweden found it more problematic to discuss the
      advantages and disadvantages of sick leave with patients and to issue a
      prolongation of a sick-leave period initiated by another physician. GPs in Norway
      more often worried that patients would go to another physician if they did not
      issue a certificate, and a higher proportion of Norwegian GPs found it
      problematic to handle situations where they and their patient disagreed on the
      need for sick leave. CONCLUSIONS: The study confirms that many GPs experience
      sickness absence consultations as problematic. However, there were differences
      between the two countries in GPs' experiences, which may be linked to differences
      in social security regulations and the organization of GP services. Possible
      causes and consequences of national differences should be addressed in future
      studies.

PMID- 22375616
TI  - Norgestrel may be a potential therapy for retinal degenerations.
AB  - Retinal degenerations cover a broad spectrum of diseases, retinitis pigmentosa
      being the most common inherited retinal degeneration. It remains an untreatable
      disorder, partly owing to its genetic complexity and variability. Gene therapies,
      stem cell transplantation and administration of slow release growth factors are
      some of the treatments currently under development for the treatment of this
      disease. More recently, steroid hormones, now known to have functions within the
      CNS aside from their traditional targets, have been suggested as potential
      therapeutic agents. Progestogenic hormones are thought to modulate pro-survival
      pathways in the retina and since these hormones are produced naturally in the
      body their value as potential therapeutic agents is clear. Current data detailing
      the pro-survival effects of progestogens in the brain and particularly in the eye
      will be discussed.

PMID- 22375617
TI  - Analysis of factors influencing accuracy and complications in CT-guided lung
      biopsy.
AB  - INTRODUCTION: This study aimed to analyze factors influencing accuracy and
      complications in patients who underwent computed tomography (CT)-guided lung
      biopsy at our medical center. MATERIAL AND METHODS: This study included all 107
      patients (72 men, 35 women; mean age, 69 years; range, 41-83 years) who underwent
      CT-guided lung biopsy between January 2006 and October 2009. CT fluoroscopy was
      used in 45.7% of cases. Final diagnosis, when surgical resection was performed,
      was histopathological diagnosis from the lung lesion specimen, and when resection
      was not performed, clinical diagnosis after >=6 months of follow-up. The accuracy
      of lung biopsy was assessed by comparison of biopsy results and final diagnosis.
      The influence of factors on accuracy was statistically analyzed. RESULTS:
      Accuracy of CT-guided lung biopsy was 89.4%. None of the factors, including
      lesion size, lesion depth from pleura, lesion location, patient position, final
      diagnosis, and use or non-use of CT fluoroscopy, had any significant influence on
      accuracy. The only complications were Grade 1 and 2 pneumothorax and Grade 1
      pulmonary bleeding. The incidence of pneumothorax and bleeding was significantly
      increased with smaller lesion size and significantly increased with greater
      lesion depth. In patients with pulmonary emphysema, bleeding was significantly
      less (p = 0.022). When CT fluoroscopy was used, bleeding was significantly
      increased (p < 0.001). CONCLUSIONS: None of the factors had any significant
      influence on accuracy. The incidence of pneumothorax and bleeding was affected by
      lesion size and lesion depth. When CT fluoroscopy was used, bleeding was
      significantly increased.

PMID- 22375618
TI  - A novel design of ventricular assist device: an in vitro feasibility study.
AB  - Left ventricular assist devices (LVADs) work as a bypass between the left
      ventricular apex and the ascending aorta. The surgical procedure for their
      insertion requires the opening of the cardiac cavities and the dissection of the
      great vessels, the blood is constrained to flow through the device components and
      the risk can be run of thrombogenesis, haemolysis and infections. A possible
      strategy to overcome this limitation consists in utilizing external systems that
      assist the heart in its contraction from the outside without directly
      transporting the blood. In this study we conduct the feasibility analysis of a
      novel external LVAD design that does not require the opening of the cardiac
      cavities and the dissection of the great vessels and that allows the removal
      procedure to be easily achieved. The device, including a stepper motor, three
      metallic wires and three elastic elements, works alternatively between a
      contraction condition where it induces an elastic compulsion on the heart and a
      release condition where it elastically releases the organ. The values of force
      acting on the wires and the values of current supplied to the motor were measured
      and utilized for a preliminary study design. The experimental measurements
      demonstrated the feasibility of the system.

PMID- 22375619
TI  - Synthesis of a multinanoparticle-embedded core/mesoporous silica shell structure
      as a durable heterogeneous catalyst.
AB  - A multi-nanoparticle-embedded amorphous aluminum/magnesium oxides (AAMO)
      core/mesoporous silica (mSiO(2)) shell structure has been successfully
      synthesized by calcining the presynthesized catalyst precursor-containing layered
      double hydroxide (LDH) core/mesoporous silica shell composite. The well-dispersed
      catalytic nanoparticles were fixed at the interface between AAMO core and
      mesoporous SiO(2) shell, i.e., at the inner pore mouths of the mesoporous SiO(2)
      shell, which could effectively prevent nanoparticles from growth and/or
      aggregation with each other and in the meantime allow efficient access of
      reactants to the catalytic NPs. The final core/shell composite was found to be an
      efficient and highly recyclable heterogeneous catalyst.

PMID- 22375620
TI  - Silver binding by humic acid as determined by equilibrium ion-exchange and
      dialysis.
AB  - One of the major challenges in environmental analytical chemistry is to develop
      methods for determining metal speciation in natural waters that contain low metal
      concentrations and dissolved organic matter (DOM). Because of its complex
      heterogeneous nature, metal binding to DOM cannot be predicted accurately using
      equilibrium models. Two independent speciation methods, the equilibrium ion
      exchange technique (IET) and equilibrium dialysis (EqD), were used to determine
      silver binding by standard Suwannee River humic acid. Both approaches gave very
      similar results, although for a given silver loading, the concentration of free
      silver obtained by IET was somewhat higher than that determined by EqD. Our
      results suggest that any high-affinity binding sites present within the humic
      acid are likely saturated at [Ag(T)] > 10(-9) M. This comparison of free metal
      ion concentrations with two independent methods provides useful speciation
      information in the absence of reliable complexation constants for the reaction of
      silver with humic acid.

PMID- 22375623
TI  - Comprehensive colorimetric study of anthocyanic copigmentation in model
      solutions. Effects of pH and molar ratio.
AB  - New colorimetric variables have been defined in the uniform CIELAB color space to
      assess the quantitative and qualitative color changes induced by copigmentation
      and their incidence on visual perception. The copigmentation process was assayed
      in model solutions between malvidin 3-glucoside and three phenolic compounds
      (catechin, epicatechin, and caffeic acid) as a function of the pH and the
      pigment/copigment molar ratio. Along the pH variation, the greatest magnitude of
      copigmentation was obtained at pH 3.0, being significantly higher with
      epicatechin and caffeic acid. At high acidic pH, the main contribution of
      copigmentation to the total color was qualitative, whereas between pH 2.0 and
      4.0, the main colorimetric contribution was quantitative. The contribution of
      epicatechin and caffeic acid to the color changes was more marked for the
      quantitative characteristics. On contrast, particularly at higher pH values, the
      qualitative contribution was more important in catechin copigmented solutions.
      Increasing copigment concentration induced perceptible color changes at molar
      ratios higher than 1:2, consisting in a bluish and darkening effect of the
      anthocyanin solutions. Among the different CIELAB attributes, hue difference was
      the best correlated parameter with the increase of copigment concentration,
      proving the relevance of this physicochemical phenomenon on the qualitative
      changes of anthocyanin color.

PMID- 22375622
TI  - DNA conjugated SWCNTs enter endothelial cells via Rac1 mediated macropinocytosis.
AB  - Several applications of single-walled carbon nanotubes (SWCNT) as nanovectors in
      biological systems have been reported, and several molecular pathways of cellular
      entry have been proposed. We employed transmission electron microscopy, confocal
      fluorescent microscopy, and UV-vis spectroscopic analysis to confirm the
      internalization of DNA-SWCNT in human umbilical vein endothelial cells.
      Additionally, by using pharmacological inhibitors as well as genetic approaches,
      we have found that SWCNT is endocytosed through Rac1- GTPase mediated
      macropinocytosis in normal endothelial cells.

PMID- 22375624
TI  - Birth by cesarean section is associated with elevated neonatal plasma levels of
      dimethylarginines.
AB  - BACKGROUND: This study was undertaken to compare the effects of vaginal delivery
      and cesarean section on the L-arginine-nitric oxide system by measuring levels of
      L-arginine, an endogenous nitric oxide synthase antagonist asymmetric
      dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in the cord blood
      and postnatally. METHODS: Plasma samples were obtained from the umbilical vein
      and artery at birth and from peripheral venous blood on the second postnatal day
      in 30 full-term newborn infants: 10 born vaginally and 20 born by cesarean
      section. RESULTS: After vaginal delivery, ADMA concentration was higher in the
      umbilical vein than in the umbilical artery (mean 1.06 vs 0.90 umol/L [P =
      0.027]); and ADMA level fell after birth to 0.66 umol/L on the second postnatal
      day (P = 0.007 vs umbilical artery). Newborns born by cesarean section had
      similar ADMA levels in umbilical arterial and venous blood, 1.19 and 1.18 umol/L,
      and the ADMA level fell to 0.84 umol/L by the second postnatal day (P < 0.001).
      Vaginal birth induced neither significant umbilical venoarterial difference nor a
      postnatal fall in SDMA. After cesarean section, SDMA was essentially the same in
      umbilical vein, umbilical artery and postnatal peripheral vein samples. At 2 days
      of age, both ADMA and SDMA levels stayed higher in infants born by cesarean
      section than in vaginally born infants. CONCLUSIONS: ADMA level falls after both
      vaginal and cesarean birth, whereas SDMA level does not. The higher ADMA level
      after cesarean birth compared with vaginal birth may contribute to decreased
      nitric oxide production and bioavailability in neonatal vascular beds.

PMID- 22375627
TI  - A glycine betaine importer limits Salmonella stress resistance and tissue
      colonization by reducing trehalose production.
AB  - Mechanisms by which Salmonella establish chronic infections are not well
      understood. Microbes respond to stress by importing or producing compatible
      solutes, small molecules that stabilize proteins and lipids. The Salmonella locus
      opuABCD (also called OpuC) encodes a predicted importer of the compatible solute
      glycine betaine. Under stress conditions, if glycine betaine cannot be imported,
      Salmonella enterica produce the disaccharide trehalose, a highly effective
      compatible solute. We demonstrate that strains lacking opuABCD accumulate more
      trehalose under stress conditions than wild-type strains. DeltaopuABCD mutant
      strains are more resistant to high-salt, low-pH and -hydrogen peroxide,
      conditions that mimic aspects of innate immunity, in a trehalose-dependent
      manner. In addition, DeltaopuABCD mutant strains require the trehalose production
      genes to out-compete wild-type strains in mice and macrophages. These data
      suggest that in the absence of opuABCD, trehalose accumulation increases
      bacterial resistance to stress in broth and mice. Thus, opuABCD reduces bacterial
      colonization via a mechanism that limits trehalose production. Mechanisms by
      which microbes limit disease may reveal novel pathways as therapeutic targets.

PMID- 22375628
TI  - Detection of alcohol use in the second trimester among low-income pregnant women
      in the prenatal care settings in Jefferson County, Alabama.
AB  - BACKGROUND: Prenatal alcohol use, a leading preventable cause of birth defects
      and developmental disabilities, remains a prevalent public health concern in the
      United States. This study aims to detect the proportion and correlates of
      prenatal alcohol use in the prenatal care settings in Alabama. Prenatal care
      settings were chosen because of their potential as stable locations to screen for
      and to reduce prenatal alcohol use within a community. METHODS: We conducted a
      cross-sectional study of 3,046 women in the 22 and 23 weeks of gestation who
      sought prenatal care in 8 community-based public clinics and participated in the
      Perinatal Emphasis Research Center project in Jefferson County, Alabama, from
      1997 to 2001. Frequency and quantity of alcohol use in the past 3 months were
      assessed by research nurses during face-to-face interviews. We conducted logistic
      regression analyses to calculate adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) of correlates of prenatal alcohol use. RESULTS: Participants were
      predominantly young, African American, and unmarried, 86.5% on Medicaid. The
      proportion of alcohol use in the second trimester of pregnancy was 5.1%; 0.3% of
      women reported 4 or more drinks on a drinking day to research nurses. Older
      maternal age (OR = 1.11; 95% CI = 1.08 to 1.15), use of welfare (OR = 1.43; 95%
      CI = 1.02 to 2.02), and male partner-perpetrated violence (OR = 2.96; 95% CI =
      1.92 to 4.56) were positively associated with elevated risk of prenatal alcohol
      use. Protective factors included higher levels of self-esteem (OR = 0.94; 95% CI
      = 0.89 to 0.98) and more years of education (OR = 0.88; 95% CI = 0.78 to 0.98).
      CONCLUSIONS: Prenatal alcohol use remains a public health issue among low-income
      pregnant women in Jefferson County, Alabama. Research nurses detected it in the
      second trimester. Future studies need to encourage screening for prenatal alcohol
      use in the prenatal care settings by obstetrician-gynecologists, family
      physicians, nurses, and midwives. Combined interventions to educate and empower
      women and strengthen families are needed.

PMID- 22375629
TI  - Reduction of carbon monoxide by [(TMTAA)Rh]2 to form a dimetal ketone complex.
AB  - Benzene solutions of [(TMTAA)Rh](2) (1) react with CO (P(CO) = 0.8-20 atm; T =
      298 K) by cleaving the Rh(II)-Rh(II) bond to form dirhodium(III) ketone (TMTAA)Rh
      C(O)-Rh(TMTAA) [2; nu(CO) = 1726 cm(-1); (1)J(103)Rh(13)C(O)(103)Rh = 45 Hz].
      Thermodynamic values for the reaction of 1 with CO to form 2 were evaluated from
      equilibrium constant measurements [K(1)(298 K) = 5.0(0.6) * 10(3), DeltaG(1)
      degrees (298 K) = -5.0(0.1) kcal mol(-1), DeltaH(1) degrees  = -14(1) kcal mol(
      1), and DeltaS(1) degrees  = -30(3) cal K(-1) mol(-1)].

PMID- 22375631
TI  - Sexual self-disclosure among university women.
AB  - Although there has been considerable research about self-disclosure, there has
      been a lack of research regarding disclosure of sexual topics. In order to
      increase our understanding of sexual self-disclosure (SSD), a scale was developed
      to measure SSD, and 10 variables were tested as predictors of SSD. The subjects
      were 203 unmarried university females aged 18-22. SSD was measured separately for
      each of the target groups of mother, father, close friend, and dating partner.
      Correlation and multiple regression analyses were performed separately for virgin
      and non-virgin subjects. The one variable which was significant for each of the
      target groups in each of the analyses was sexual comfort level of the target
      person. The variables of sex guilt and target person's sexual attitudes were
      significant for disclosure to each of the target groups among the nonvirgin
      subjects but to only some of the target groups among the virgin subjects. The
      remaining seven predictor variables were significant for at least one of the
      target groups. In the multiple regression models, the proportion of variance
      explained ranged from 28% to 58%. The results indicate the value of controlling
      for both target group and virginity status when analyzing the relationship of
      predictor variables to SSD.

PMID- 22375632
TI  - Dating couples' disagreements over the desired level of sexual intimacy.
AB  - Sixty-seven female and 54 male college students participated in a study of sexual
      disagreements in which the man desired to engage in a higher level of sexual
      activity than did the woman. Participants kept an ongoing record of dates and
      disagreements and provided descriptive information about some of these. We had
      three goals: (a) to determine how frequently this type of disagreement occurs in
      dating relationships; (b) to determine the types and frequencies of the various
      strategies that men use when their partner indicates that she is unwilling to
      engage in a particular sexual activity; and (c) to describe the characteristics
      of disagreement situations and relate these to male compliance with the woman's
      refusal. One or more disagreements were reported by 47% of participants, but
      disagreements occurred on only 7% of reported dates. In 61% of the disagreement
      situations, the man complied with the woman's refusal without question. Verbal
      and/or physical coercion was reported in 25% of the disagreement situations.
      These results suggest that although sexual coercion is a part of some dating
      relationships, it does not characterize our dating system to the degree suggested
      by Clark and Lewis (1977). Characteristics of the disagreement situation and
      their relationship to male compliance are reported and discussed.

PMID- 22375633
TI  - Sexual activity and preference: Six quantifiable dimensions.
AB  - We present a new multidimensional measure of sexual activity and preference that
      may be of use to researchers and practitioners who work in clinical settings
      involving sex-related problems. The questionnaire contains six subscales to
      measure amounts of sexual activity and six subscales to measure degree of
      preference for those activities. The 12 subscales have good to excellent
      reliabilities, and they all appear to have content, construct, and factorial
      validity.

PMID- 22375634
TI  - Erotic value of female distress in sexually explicit photographs.
AB  - The extent to which distress of the female model contributed to the erotic value
      of sexually explicit photographs of women in bondage was studied for a sample of
      54 young-adult college males. In addition, subjects were categorized by level of
      antisociality and level of facial-decoding skill with the prediction that the
      erotic value of a model in distress would be greatest for subjects departing most
      from social values (antisociality) and most capable of recognizing emotions as
      facially displayed by another person (facial decoding). There was an overall
      sadism effect. Most of the men reported pictures depicting a distressed model in
      bondage to be more sexually stimulating than pictures in which the female model
      displayed positive affect. The erotic value of distressed females in bondage was
      greatest when subjects combined greater anti-sociality and better facial-decoding
      skill.

PMID- 22375635
TI  - Men's self-reports of unwanted sexual activity.
AB  - We investigated men's experience with unwanted sexual activity-including unwanted
      kissing, petting, or intercourse-engaged in because of physical or psychological
      pressure or from societal expectations about male sexuality. We developed a
      questionnaire asking if respondents had ever engaged in unwanted sexual activity
      for any of 51 reasons. This questionnaire was administered to 507 men and 486
      women. More women (97.5%) than men (93.5%) had experienced unwanted sexual
      activity; more men (62.7%) than women (46.3%) had experienced unwanted
      intercourse. Using factor analysis, we grouped the 51 questionnaire items into 13
      general reasons; we then compared percentages of men and women who had engaged in
      unwanted sexual activity for these 13 reasons. There were seven sex differences
      in reasons for unwanted sexual activity: Five were more frequent for women than
      men; two reasons were more frequent for men than women-peer pressure and desire
      for popularity. There were eight sex differences in reasons for unwanted
      intercourse; more men than women had engaged in unwanted intercourse for all
      eight. The double standard for male and female sexuality and implications for
      therapy are discussed.

PMID- 22375630
TI  - RNA-Seq quantification of the human small airway epithelium transcriptome.
AB  - BACKGROUND: The small airway epithelium (SAE), the cell population that covers
      the human airway surface from the 6th generation of airway branching to the
      alveoli, is the major site of lung disease caused by smoking. The focus of this
      study is to provide quantitative assessment of the SAE transcriptome in the
      resting state and in response to chronic cigarette smoking using massive parallel
      mRNA sequencing (RNA-Seq). RESULTS: The data demonstrate that 48% of SAE
      expressed genes are ubiquitous, shared with many tissues, with 52% enriched in
      this cell population. The most highly expressed gene, SCGB1A1, is characteristic
      of Clara cells, the cell type unique to the human SAE. Among other genes
      expressed by the SAE are those related to Clara cell differentiation, secretory
      mucosal defense, and mucociliary differentiation. The high sensitivity of RNA-Seq
      permitted quantification of gene expression related to infrequent cell
      populations such as neuroendocrine cells and epithelial stem/progenitor cells.
      Quantification of the absolute smoking-induced changes in SAE gene expression
      revealed that, compared to ubiquitous genes, more SAE-enriched genes responded to
      smoking with up-regulation, and those with the highest basal expression levels
      showed most dramatic changes. Smoking had no effect on SAE gene splicing, but was
      associated with a shift in molecular pattern from Clara cell-associated towards
      the mucus-secreting cell differentiation pathway with multiple features of cancer
      associated molecular phenotype. CONCLUSIONS: These observations provide insights
      into the unique biology of human SAE by providing quantitative assessment of the
      global transcriptome under physiological conditions and in response to the stress
      of chronic cigarette smoking.

PMID- 22375636
TI  - Empirical tests of sexual selection theory: Predictions of sex differences in
      onset, intensity, and time course of sexual arousal.
AB  - An evolutionary model of sexual behavior was used to generate predictions about
      sex differences in sexual arousal. Survey instruments were used to test these
      predictions with 388 adolescents, aged 12-18, from varying socioeconomic strata
      and geographic regions. Boys reported that their first arousal occurred at the
      start of puberty or before, usually in response to a visual stimulus, whereas
      girls generally reported first arousal as occurring 2-3 or more years after
      puberty, within a social/romantic context. The modal boy reported sexual arousal
      as occurring several times daily, the modal girl once or twice a week. Boys
      reported their arousal to be more discriminable, of greater intensity, and more
      distracting than the girls'. The sexes differed in attitudes related to sexual
      behavior. However, when reporting emotions and feelings coterminous with sexual
      arousal, the sexes did not differ. Retrospective college samples of 262 students
      from West Coast colleges replicated the adolescent data. A survey of 280 East
      Coast college students found that women's sexual arousal was significantly more
      partner-dependent than men's. Results were interpreted as supporting evolutionary
      models of sex differences in sexuality.

PMID- 22375637
TI  - A scale for the comparison of the sexual attitudes of adolescents and their
      parents.
AB  - We developed a 14-item Attitudes Toward Sexuality Scale (ATSS) to compare the
      sexual attitudes of early, middle, and late adolescents and their parents. One
      hundred forty-one adolescents between the ages of 12 and 20 and their parents
      completed a questionnaire consisting of the ATSS and demographic information. The
      Cronbach alpha reliability coefficient for the adolescents was .75, and for the
      parents it was .84. A principal components analysis revealed four major
      dimensions of the scale: a large General factor, Legality/Morality, Alternative
      Modes of Sexual Expression, and Individual Rights. The correlation pattern
      between the ATSS and subscales of the Sex Knowledge and Attitudes Test, as well
      as with certain demographic variables, supports the construct validity of the
      ATSS. This is, therefore, a scale which may be used for research in which the
      sexual attitudes of adults and adolescents of various ages are to be measured and
      compared.

PMID- 22375638
TI  - Social cognitions about adult male victims of female sexual assault.
AB  - Although men are far less likely than women to be victims of heterosexual
      assault, such cases have been reported with increasing frequency in recent years.
      We compared social judgments about male and female victims of heterosexual and
      homosexual rape and tested hypotheses concerning social cognitions that are
      assumed to underlie a male rape mythology. In a 2 * 2 * 2 design, 77 male and 89
      female subjects made a series of judgments about a sexual assault case in which
      sex of victim and sex of assailants were manipulated. Consistent with the
      hypotheses, the male victim of sexual assault by females was judged more likely
      to have initiated or encouraged the sex acts, and more enjoyment and less stress
      were attributed to him. This pattern of results was more pronounced among male
      subjects. The results are discussed in relation to stereotypic beliefs concerning
      male sex roles, sexual motivation, and sexual functioning that are likely to
      affect the social cognitions of both observers and male victims of heterosexual
      assault.

PMID- 22375639
TI  - The periodic table model of the gender transpositions: Part II. Limerent and
      lusty sexual attractions and the nature of bisexuality.
AB  - I propose a theory that puts the notion of two sexual attractions into a precise,
      testable form, and then I mesh it with the periodic table model of the gender
      transpositions described previously (Pillard & Weinrich, 1987). I define a
      limerent sexual attraction, active in eroticizing the physical and personality
      characteristics of a particular Limerent Object, and a lusty sexual attraction,
      active in producing erotic arousal when encountering a new Lusty Object. Three
      hypotheses then account for much of what we know about sexual orientation: (a)
      Limerence and lustiness are experienced by both men and women-but there is an
      average difference in the ease with which each can be elicited in a particular
      sex. Limerence is experienced by most women in our culture as an autonomously
      arising desire, whereas lustiness, when it occurs, is experienced mostly as a
      reaction to particular stimuli. Lustiness is experienced by most men in our
      culture as an autonomously arising desire, whereas limerence, when it occurs, is
      experienced mostly in reaction to particular stimuli. (b) In some people the
      limerent attraction can be indifferent (or nearly so) to the sex or gender of the
      Limerent Object. (c) The lusty attraction is rarely indifferent to the sex or
      gender of the Lusty Object. Individuals may vary in their readiness to respond to
      the two kinds of attraction. Some of this variability can be understood in the
      light of the periodic table model described previously, and some of it can be
      understood in the light of cultural conditioning and socialization. The result is
      a theory that deduces many of the major facts about sexual orientation from only
      a small number of hypotheses.

PMID- 22375640
TI  - Analgesia produced in women by genital self-stimulation.
AB  - This study investigated the relative effectiveness of specific genital regional
      self-stimulation in elevating pain thresholds. Anecdotal reports in humans
      suggest that sexual activity and orgasm decrease a wide variety of human
      responses to pain and touch, but the phenomenon has not been evaluated
      objectively. Two types of self-stimulation, pressure and pleasurable, were
      applied by 10 women to the anterior vaginal wall, the posterior vaginal wall, and
      the clitoris. Significant increases in pain thresholds but not tactile thresholds
      occurred when pressure stimulation was applied to the anterior wall of the vagina
      or when "pleasurable" self-stimulation was applied to any of the three areas.
      Tactile thresholds were not significantly affected by any genital stimulation
      condition. However, there was a significant increase in tactile threshold but not
      pain thresholds in the distraction control condition. On the basis of these
      findings, we conclude that (a) a sensation of pleasure evoked by genital
      stimulation can elevate pain thresholds, (b) these pleasurable stimuli were not
      general "distractants" because they elevated pain thresholds but not tactile
      thresholds differentially, and (c) genital pleasurable stimuli activate an
      analgesic process that is distinct from a distraction process.

PMID- 22375641
TI  - The sexually experienced woman: Multiple sex partners and sexual satisfaction.
AB  - It has been suggested that women who have had more than one sex partner differ
      from those who have had only one, both in their background and in their current
      functioning (in the forms of attitudes, partner interaction, sexual satisfaction,
      desired changes in their sex life, and other behaviors). To explore these issues,
      we distributed a questionnaire to a sample of 868 nurses located in 15 states.
      For most variables, there were no significant differences among those with only
      one lifetime partner, those with few (2-5) partners, and those with many (6 or
      more) partners. Those with more partners did report having intercourse earlier,
      reaching orgasm earlier, and pretending to reach orgasm more often. Those with
      many partners indicated their partners more often delayed orgasm until after
      their own first orgasm. They also expressed more concern about a lack of interest
      in and a lack of adequate foreplay by their partners. Those women with a few
      partners expressed the least psychological sexual satisfaction (79%).

PMID- 22375642
TI  - Incidence of psychometric symptoms in rape victims.

PMID- 22375644
TI  - Effects of a contraceptive hormone, danazol, on male sexual functioning.

PMID- 22375643
TI  - Women's attitudes toward and experience with sexually explicit materials.

PMID- 22375645
TI  - Penis size increase between flaccid and erect states: An analysis of the Kinsey
      data.

PMID- 22375646
TI  - The modification of urinary urgency during sexual arousal.

PMID- 22375647
TI  - Nonhomosexual gender dysphoria.

PMID- 22375648
TI  - Sexual attitudes and behavior of high school students in relation to background
      and contextual factors.

PMID- 22375650
TI  - Pornography and sex education.

PMID- 22375649
TI  - The sexuality of prostitutes: Sexual enjoyment reported by "streetwalkers".

PMID- 22375651
TI  - Clomipramine in the treatment of premature ejaculation.

PMID- 22375652
TI  - Nocturnal emission and masturbatory frequency relationships: A 19th-century
      account.

PMID- 22375653
TI  - Factors related to sexual counseling of physically disabled adults.

PMID- 22375654
TI  - Incidence and nature of male genital exposure behavior as reported by college
      women.

PMID- 22375656
TI  - Rape rates and the circulation rates of adult magazines.

PMID- 22375655
TI  - Forced sex on dates: It happens to men, too.

PMID- 22375657
TI  - The relationship of age, sex guilt, and sexual experience with female sexual
      fantasies.

PMID- 22375658
TI  - College coaches' attitudes toward pregame sex.

PMID- 22375659
TI  - Alienation, self-image, and the importance of support groups for the wives of
      transvestites.

PMID- 22375660
TI  - Evaluating the effectiveness of the SECS' surrogate-assisted sex therapy model.

PMID- 22375661
TI  - Perceived parental rearing patterns of homosexual and heterosexual men.

PMID- 22375663
TI  - Sex differences in heterosexuals' attitudes toward homosexuals: It depends upon
      what you ask.

PMID- 22375662
TI  - College students' acceptance of adoption and five alternative fertilization
      techniques.

PMID- 22375664
TI  - Extrapremarital intercourse: Attitudes toward a neglected sexual behavior.

PMID- 22375665
TI  - Attitudes toward rape.

PMID- 22375666
TI  - The relationship between parent-child communication about sexuality and college
      students' sexual behavior and attitudes as a function of parental proximity.

PMID- 22375667
TI  - Female urethral explusions evoked by local digital stimulation of the G-spot:
      Differences in the response patterns.

PMID- 22375668
TI  - Concentrations of fructose in female ejaculate and urine: A comparative
      biochemical study.

PMID- 22375669
TI  - A critical analysis of recent research on violent erotica.

PMID- 22375670
TI  - Research on "violent erotica": A reply.

PMID- 22375672
TI  - A reply to Malamuth and Donnerstein and Linz.

PMID- 22375671
TI  - A critical analysis of "a critical analysis of recent research on violent
      erotica".

PMID- 22375673
TI  - Donnerstein, Malamuth, and Mould: The conduct of research and the nature of
      inquiry.

PMID- 22375674
TI  - Female primary orgasmic dysfunction: Masters and Johnson versus DSM-III-R on
      diagnosis and incidence.

PMID- 22375675
TI  - Balancing the rights of subjects, scientists, and society: 10 principles for
      human subject committees.

PMID- 22375676
TI  - Sexual liberation, old-fashioned outlook, and authoritarianism: A comment on
      Kelley.

PMID- 22375677
TI  - Wanted: 3 Cs for 4S.

PMID- 22375678
TI  - Editor's report.

PMID- 22375681
TI  - Gender differences in quality of life outcomes of HIV/AIDS treatment in the
      latent feminization of HIV epidemics in Vietnam.
AB  - Understanding gender-specific predictors of Health-related Quality of Life (HRQL)
      outcomes of HIV/AIDS treatment is necessary in the latent feminization of HIV
      epidemics in Vietnam. This study assessed HRQL and its predictors among men and
      women with HIV/AIDS. We conducted a cross-sectional study of 155 patients (36.8%
      women, mean age=31.4) registering for antiretroviral treatment (ART) at Vietnam
      Sweden Uong Bi General Hospital, Quang Ninh Province. The Vietnamese version of
      the World Health Organization Quality of Life HIV brief version (WHOQOL-HIV BREF)
      was developed. Factor analysis was applied to assess the construct validity of
      the measurement. Six major domains of the Vietnamese WHOQOL-HIV BREF were
      determined, namely physical; performance; morbidity; environment; psychological;
      and social support. Internal consistency reliability of the six domains ranged
      from 0.52 to 0.71. Multivariate linear regression models, constructed using step
      wise forward selection, determined different predictors of HRQL domain scores in
      men and women with HIV/AIDS. The results showed that men reported higher scores
      or better in Morbidity (p=0.02), Environment (p=0.07) and Psychological
      dimensions (p=0.02); meanwhile, women had higher scores in Performance (p=0.09).
      Alcohol and injection drug use negatively predicted HRQL outcomes in both men and
      women. Employment was associated with better performance in men, and better
      physical but poorer environment status in women. Female patients who have a child
      experienced decrements in social support, psychological, environment, and
      performance. Findings of this study highlight the need to develop comprehensive
      interventions for HIV/AIDS patients, including HIV/AIDS treatment support and
      gender-specific impact mitigation interventions strategies.

PMID- 22375682
TI  - Devolution and public perceptions and experience of health services in Pakistan:
      linked cross sectional surveys in 2002 and 2004.
AB  - BACKGROUND: The government of Pakistan introduced devolution in 2001.
      Responsibility for delivery of most health services passed from provincial to
      district governments. Two national surveys examined public opinions, use, and
      experience of health services in 2001 and 2004, to assess the impact of
      devolution on these services from the point of view of the public. METHODS: A
      stratified random cluster sample drawn in 2001 and revisited in 2004 included
      households in all districts. Field teams administered a questionnaire covering
      views about available health services, use of government and private health
      services, and experience and satisfaction with the service. Focus groups in each
      community discussed reasons behind the findings, and district nazims (elected
      mayors) and administrators commented about implementation of devolution.
      Multivariate analysis, with an adjustment for clustering, examined changes over
      time, and associations with use and satisfaction with services in 2004. RESULTS:
      Few of 57,321 households interviewed in 2002 were satisfied with available
      government health services (23%), with a similar satisfaction (27%) among 53,960
      households in 2004. Less households used government health services in 2004 (24%)
      than in 2002 (29%); the decrease was significant in the most populous province.
      In 2004, households were more likely to use government services if they were
      satisfied with the services, poorer, or less educated. The majority of users of
      government health services were satisfied; the increase from 63% to 67% between
      2002 and 2004 was significant in two provinces. Satisfaction in 2004 was higher
      among users of private services (87%) or private unqualified practitioners (78%).
      Users of government services who received all medicines from the facility or who
      were given an explanation of their condition were more likely to be satisfied.
      Focus groups explained that people avoid government health services particularly
      because of bad treatment from staff, and unavailable or poor quality medicines.
      District nazims and administrators cited problems with implementation of
      devolution, especially with transfer of funds. CONCLUSIONS: Under devolution, the
      public did not experience improved government health services, but devolution was
      not fully implemented as intended. An ongoing social audit process could provide
      a basis for local and national accountability of health services.

PMID- 22375683
TI  - Design and fabrication of gecko-inspired adhesives.
AB  - Recently, there has been significant interest in developing dry adhesives
      mimicking the gecko adhesive system, which offers several advantages compared to
      conventional pressure-sensitive adhesives. Specifically, gecko adhesive pads have
      anisotropic adhesion properties; the adhesive pads (spatulae) stick strongly when
      sheared in one direction but are non-adherent when sheared in the opposite
      direction. This anisotropy property is attributed to the complex topography of
      the array of fine tilted and curved columnar structures (setae) that bear the
      spatulae. In this study, we present an easy, scalable method, relying on
      conventional and unconventional techniques, to incorporate tilt in the
      fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive
      system, which provides anisotropic adhesion properties. We measured the
      anisotropic adhesion and friction properties of samples with various tilt angles
      to test the validity of a nanoscale tape-peeling model of spatular function.
      Consistent with the peel zone model, samples with lower tilt angles yielded
      larger adhesion forces. The tribological properties of the synthetic arrays were
      highly anisotropic, reminiscent of the frictional adhesion behavior of gecko
      setal arrays. When a 60 degrees  tilt sample was actuated in the gripping
      direction, a static adhesion strength of ~1.4 N/cm(2) and a static friction
      strength of ~5.4 N/cm(2) were obtained. In contrast, when the dry adhesive was
      actuated in the releasing direction, we measured an initial repulsive normal
      force and negligible friction.

PMID- 22375684
TI  - What differentiates primary care physicians who predominantly prescribe diuretics
      for treating mild to moderate hypertension from those who do not? A comparative
      qualitative study.
AB  - BACKGROUND: Thiazide diuretics are cost-effective for the treatment of mild to
      moderate hypertension, but physicians often opt for more expensive treatment
      options such as angiotensin II receptor blockers or angiotensin converting enzyme
      inhibitors. With escalating health care costs, there is a need to elucidate the
      factors influencing physicians' treatment choices for this highly prevalent
      chronic condition. The purpose of this study was to describe the characteristics
      of physicians' decision-making process regarding hypertension treatment choices.
      METHODS: A comparative qualitative study was conducted in 2009 in the Canadian
      province of Quebec. Overall, 29 primary care physicians--who are also
      participating in an electronic health record research program--participated in a
      semi-structured interview about their prescribing decisions. Physicians were
      categorized into two groups based on their patterns of prescribing
      antihypertensive drugs: physicians who predominantly prescribe diuretics, and
      physicians who predominantly prescribe drug classes other than diuretics. Cases
      of hypertension that were newly started on antihypertensive therapy were
      purposely selected from each physician's electronic health record database. Chart
      stimulated recall interview, a technique utilizing patient charts to probe recall
      and provide context to physician decision-making during clinical encounters, was
      used to elucidate reasons for treatment choices. Interview transcripts were
      synthesized using content analysis techniques, and factors influencing
      physicians' decision making were inductively generated from the data. RESULTS: We
      identified three themes that differentiated physicians who predominantly
      prescribe diuretics from those who predominantly prescribe other drug classes for
      the initial treatment of mild to moderate hypertension: a) perceptions about the
      efficacy of diuretics, b) preferred approach to hypertension management and, c)
      perceptions about hypertension guidelines. Specifically, physicians had
      differences in beliefs about the efficacy, safety and tolerability of diuretics,
      the most effective approach for managing mild to moderate hypertension, and in
      aggressiveness to achieve treatment targets. Marketing strategies employed by the
      pharmaceutical industry and practice experience appear to contribute to these
      differences in management approach. CONCLUSIONS: Physicians preferring more
      expensive treatment options appear to have several misperceptions about the
      efficacy, safety and tolerability of diuretics. Efforts to increase physicians'
      prescribing of diuretics may need to be directed at overcoming these
      misperceptions.

PMID- 22375685
TI  - Eudragit RL100 based microspheres for ocular administration of azelastine
      hydrochloride.
AB  - In the present study, potential of polymeric microspheres for treatment of
      allergic conjunctivitis was investigated. Azelastine hydrochloride loaded
      Eudragit RL100 microspheres were prepared by solvent evaporation technique. The
      change in drug-polymer ratio on the particle size, zeta potential, entrapment
      efficiency and in vitro drug release was investigated. As Eudragit concentration
      ranged from 40 to 80 mg/ml the size range obtained was 4.18-7.36 um with positive
      zeta potential. With the increase in drug polymer ratio, the entrapment
      efficiency was increased with maximum 14.56%. In vitro release studies
      demonstrated prolonged release of the drug over the period of 6 hr. Scanning
      electron micrographs showed that microspheres were spherical with distinct solid
      dense structure. Fourier transform infrared and differential scanning calorimetry
      studies concluded slight change in peak intensities of drug in microspheres. In
      vivo studies in rat model indicated that reduction in eosinophil count number was
      more pronounced in azelastine hydrochloride microspheres than marketed
      formulation, Azelast(r).

PMID- 22375686
TI  - Evaluation of microemulsion and liposomes as carriers for oral delivery of
      transforming growth factor alpha in rats.
AB  - The aim of the present study is to develop microemulsion and liposome carrier
      systems for oral administration of transforming growth factor alpha (TGF-alpha)
      and to investigate the effects of these carrier systems on the gastrointestinal
      efficiency in rats. Microemulsion (w/o) and liposomes (MLV) were developed and
      characterised. The carrier systems were administered intragastrically by gastric
      cannula to male Wistar rats. The highest reduction in the basal acid secretion
      was observed in the microemulsion containing TGF-alpha and aprotinin group
      (TAME).The gastric mucus secretion in microemulsion containing TGF-alpha (TME)
      and TAME treatment groups increased significantly compared to the other groups.
      TGF-alpha levels in both stomach and duodenum were significantly increased in the
      TAME group. As a result, it was determined through confocal laser scanning
      microscope (CLSM) studies that exogenous-applied TGF-alpha attached to endogenous
      EGF receptors. The microemulsion formulation was found to be a more suitable
      carrier system for oral administration of TGF-alpha.

PMID- 22375688
TI  - Predictive score for early preterm birth in decisions about emergency cervical
      cerclage in singleton pregnancies.
AB  - OBJECTIVE: To develop a simple score for assessing the risk of early preterm
      delivery before 32 weeks in women with singleton pregnancies receiving emergency
      cervical cerclage. DESIGN: Retrospective study. SETTING: French tertiary care
      center from 1994 to 2006. POPULATION: A total of 134 pregnant women underwent
      emergency cervical cerclage procedure at 15-26 weeks. The analysis concerned 85
      singleton pregnancies after exclusion of women with a dilated cervix without
      visible membranes, or presenting for revision of failed prophylactic cerclage, or
      who had either preterm premature rupture of membranes or clinical signs of
      chorioamnionitis. METHODS: Multivariate logistic regression methods with rounded
      coefficients were used to develop a score to predict early preterm delivery
      before 32 weeks. MAIN OUTCOME MEASURES: Early preterm delivery before 32 weeks.
      RESULTS: The score, ranging from 0 to 15 points, was based on the following four
      criteria independently associated with early preterm delivery: obstetric history;
      cervical dilatation; membranes bulging into the vagina; and infection. Each score
      value was associated with a predicted probability of early preterm birth.
      CONCLUSIONS: The score and its associated early preterm probabilities may be a
      valuable tool to help physicians in advising women about the need for emergency
      cerclage.

PMID- 22375689
TI  - Ion size influence on the Ar solvation shells of M(+)-C6F6 clusters (M = Na, K,
      Rb, Cs).
AB  - The size-specific influence of alkali metal ions in the gradual transition from
      cluster rearrangement to solvation dynamics is investigated by means of molecular
      dynamics simulations for alkali metal cation-hexafluorobenzene systems, M(+)
      C(6)F(6) (M = Na, K, Rb and Cs), surrounded by Ar atoms. To analyze such
      transition, different small aggregates of the M(+)-C(6)F(6)-Ar(n) (n = 1, ...,
      30) type and M(+)-C(6)F(6) clusters solvated by about 500 Ar atoms are
      considered. The Ar-C(6)F(6) interaction contribution has been described using two
      different formalisms, based on the interaction decomposition in atom-bond and in
      atom-effective atom terms, which have been applied to study the small aggregates
      and to investigate the Ar solvated M(+)-C(6)F(6) clusters, respectively. The
      selectivity of the promoted phenomena from the M(+) ion size and their dependence
      from the number of Ar atoms is characterized.

PMID- 22375690
TI  - UHPLC-MS analysis of juvenile hormone II in Mediterranean corn borer (Sesamia
      nonagrioides) hemolymph using various ionization techniques.
AB  - The juvenile hormones (JHs) have been considered the most versatile hormones in
      the animal kingdom. JH-II is the most abundant JH in Sesamia nonagrioides,
      important maize pests in the Mediterranean basin. This study compared the
      sensitivities and matrix effects of four ionization modes on analyzing JH-II in
      S. nonagrioides hemolymph using ultrahigh-performance liquid chromatography-mass
      spectrometry (UHPLC-MS) in single ion monitoring (SIM) mode. The ionization
      techniques tested were electrospray ionization (ESI), atmospheric pressure
      chemical ionization (APCI), atmospheric pressure photoionization (APPI), and APPI
      with the lamp turned off, which corresponds to atmospheric pressure thermospray
      ionization (APTSI). ESI was discarded because of the high matrix effect. APPI was
      discarded because the correlation responses between solvent and matrix on the
      instrumental quality parameters were worse than those for APTSI and APCI. In our
      analytical conditions, APCI has shown the best validation parameter values. APCI
      ionization is widely available in instrumental laboratories.

PMID- 22375691
TI  - Prevalence of HIV and sexually transmitted infections among clients of female sex
      workers in Karnataka, India: a cross-sectional study.
AB  - BACKGROUND: Studies have demonstrated the significance of commercial sex work in
      the ongoing transmission of HIV and other sexually transmitted infections (STIs)
      in India. Clients of female sex workers (FSWs) are thought to be an important
      bridging population for HIV/STIs. However, there is a lack of information on
      basic characteristics of sex work clients. This study sought to describe the
      prevalence of HIV and other STIs, as well as examine the determinants of these
      pathogens among a sample of clients in south India. METHODS: Data were from a
      cross-sectional biological and behavioural survey of FSW clients from six
      districts in Karnataka State, India. The prevalence of HIV, syphilis, herpes
      simplex virus type 2 (HSV-2), chlamydia (CT) and gonorrhoea (NG) among clients
      was examined. Multivariable logistic regression models were used to analyse the
      socio-demographic, sexual behaviour and sex-work related characteristics related
      to the prevalence of each pathogen. Sampling weights and appropriate survey
      methods were utilized in regression models to account for complex sampling
      design. RESULTS: The total sample size was 2,745. The average age of clients was
      30.4 (SE:0.3). Across the total sample, the prevalence of HIV, HSV-2, syphilis
      and CT/NG was 5.6%, 28.4%, 3.6% and 2.2%, respectively. The prevalence of
      HIV/STIs varied substantially across districts, reaching statistical significance
      for HIV (p<.0001) and CT/NG (p=.005). In multivariable models, duration of paying
      for commercial sex was associated with increased risk for HIV and HSV-2 (AOR:
      1.1; 95%CI: 1.0-1.1, p<.0001). Clients with brothels as a main FSW solicitation
      site were associated with increased risk of HIV (AOR: 2.4; 95%CI: 1.2-4.7,
      p=.001), while those frequenting lodges were at increased risk for CT/NG (AOR:
      6.3; 95%CI: 1.9-20.6, p=.03). Examining co-infections, clients with HSV-2
      infections were at substantially higher risk of being HIV-positive (AOR: 10.4;
      95%CI: 6.1-17.7, p<.0001). CONCLUSIONS: This study fills in important gaps in
      knowledge regarding clients in southern India. The strong association between HIV
      and HSV-2 infections highlights the complications in designing effective
      prevention, intervention and management programs of this well-hidden population.

PMID- 22375692
TI  - Comparative effects of the marine algal toxins azaspiracid-1, -2, and -3 on
      Jurkat T lymphocyte cells.
AB  - Azaspiracids (AZA) are polyether marine toxins of dinoflagellate origin that
      accumulate in shellfish and represent an emerging human health risk. Although
      monitored and regulated in many European and Asian countries, there are no
      monitoring programs or regulatory requirements in the United States for this
      toxin group. This did not prove to be a problem until June 2009 when AZAs were
      identified in US seafood for the first time resulting in human intoxications and
      further expanding their global distribution. Efforts are now underway in several
      laboratories to better define the effects and mechanism(s) of action for the
      AZAs. Our investigations have employed Jurkat T lymphocyte cells as an in vitro
      model to characterize the toxicological effects of AZA1, AZA2, and AZA3.
      Cytotoxicity experiments employing a metabolically based dye (i.e., MTS)
      indicated that AZA1, AZA2, and AZA3 each elicited a lethal response that was both
      concentration- and time-dependent, with EC(50) values in the sub- to low
      nanomolar range. On the basis of EC(50) comparisons, the order of potency was as
      follows: AZA2 > AZA3 > AZA1, with toxic equivalence factors (TEFs) relative to
      AZA1 of 8.3-fold and 4.5-fold greater for AZA2 and AZA3, respectively. Image
      analysis of exposed cells using Nomarski differential interference contrast (DIC)
      imaging and fluorescent imaging of cellular actin indicated that the
      morphological effects of AZA1 on this cell type are unique relative to the
      effects of AZA2 and AZA3. Collectively, our data support the growing body of
      evidence suggesting that natural analogues of AZA are highly potent and that they
      may have multiple molecular targets.

PMID- 22375693
TI  - The role of the MTHFR gene in migraine.
AB  - Migraine is a common neurological disorder and is characterized by debilitating
      head pain and an assortment of additional symptoms which can include nausea,
      emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances.
      A number of genes have been implicated in the pathogenesis of this disease,
      including genes involved in regulating the vascular system. Of particular
      importance are the methylenetetrahydrofolate reductase (MTHFR) gene and the role
      it plays in migraine with aura. Migraine with aura has previously been shown to
      have a significant comorbidity with stroke, making the vascular class of genes a
      priority for migraine studies. In this report, we outline the importance of the
      MTHFR gene in migraine and also discuss the use of a genetic isolate to
      investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide
      polymorphisms showing association with migraine in the Norfolk Island population
      have been identified, thus reinforcing the potential role of MTHFR in migraine
      susceptibility. Further studies will continue to build a gene profile of variants
      involved in the complex disease migraine and improve understanding of the
      underlying genetic causes of this disorder.

PMID- 22375694
TI  - Molecular-basis of single-walled carbon nanotube recognition by single-stranded
      DNA.
AB  - Hybrids of biological molecules and single-walled carbon nanotubes (SWCNT) have
      proven useful for SWCNT sorting and are enabling several biomedical applications
      in sensing, imaging, and drug delivery. In the DNA-SWCNT system, certain short
      (10-20mer) sequences of single-stranded DNA recognize specific SWCNT, allowing
      the latter to be sorted from a chirality diverse mixture. (1) However, little is
      known about the DNA secondary structures that underlie their recognition of
      SWCNTs. Using replica exchange molecular dynamics (REMD) of multiple strands on a
      single SWCNT, we report that DNA forms ordered structures on SWCNTs that are
      strongly DNA sequence and SWCNT dependent. DNA sequence (TAT)(4) on its
      recognition partner, the (6,5) SWCNT, (1) forms an ordered right-handed helically
      wrapped barrel, stabilized by intrastrand, self-stitching hydrogen bonds and
      interstrand hydrogen bonding. The same sequence on the larger diameter (8,7)
      SWCNT forms a different and less-stable structure, demonstrating SWCNT
      selectivity. In contrast, homopolymer (T)(12), with weaker tendency for
      intrastrand hydrogen bonding, forms a distinctly left-handed wrap on the (6,5)
      SWCNT, demonstrating DNA sequence specificity. Experimental measurements show
      that (TAT)(4) selectively disperses smaller diameter SWCNTs more efficiently than
      (T)(12), establishing a relationship between recognition motifs and binding
      strength. The developing understanding of DNA secondary structure on
      nanomaterials can shed light on a number of issues involving hybrids of
      nanomaterials and biological molecules, including nanomedicine, health-effects of
      nanomaterials, and nanomaterial processing.

PMID- 22375696
TI  - Actin dynamics in development of behavioral sensitization after withdrawal from
      long-term ethanol administration to mice.
AB  - BACKGROUND AND METHODS: The present study investigated the role of actin
      depolymerizing factor (ADF) in the brain of mice after withdrawal from continuous
      ethanol (EtOH) vapor inhalation for 9 days using C57BL/6J and ADF mutant mice.
      RESULTS: C57BL/6J mice with withdrawal signs 10 hours after withdrawal from EtOH
      vapor inhalation showed transient and significant enhancement of locomotor
      activity by a single injection of EtOH (2 g/kg, i.p.) and of EtOH-induced place
      preference 3 days after withdrawal from EtOH vapor inhalation, suggesting the
      development of sensitization of locomotion activity to EtOH and of place
      preference 3 days after withdrawal from EtOH in C57BL/6J mice with EtOH physical
      dependence. The levels of ADF and G-actin in the ventral tegmental area,
      including a little bit of surrounding tissues, increased immediately (0 hours),
      10 hours, and 3 days after withdrawal from EtOH vapor. F-actin, synaptic vesicle
      associated protein 38, and postsynaptic density 95 increased 0 hours and 3 days
      after withdrawal with their decreases 10 hours after withdrawal from EtOH vapor.
      An F-actin stabilizing agent phalloidin (3 nmol/mouse/d, i.c.v., once a day)
      administered daily for 3 days after withdrawal from continuous EtOH vapor
      inhalation for 9 days significantly suppressed the increase in both EtOH-induced
      place preference and locomotor activity by a single injection of EtOH 3 days
      after withdrawal from long-term EtOH vapor inhalation for 9 days. In addition,
      the changes in behavioral sensitization in ADF mutant mice were significantly
      weaker than those observed in C57BL/6J mice (wild-type mice for ADF mutant mice).
      CONCLUSIONS: The findings presented here suggest that withdrawal from EtOH
      physical dependence causes behavioral sensitization to EtOH, which may be, at
      least in part, mediated by alternation of actin dynamics.

PMID- 22375698
TI  - Occupational safety and HIV risk among female sex workers in China: a mixed
      methods analysis of sex-work harms and mommies.
AB  - Female sex workers (FSWs) in China are exposed to multiple work-related harms
      that increase HIV vulnerability. Using mixed-methods, we explored the social
      ecological aspects of sexual risk among 348 FSWs in Beijing. Sex-work harms were
      assessed by property stolen, being underpaid or not paid at all, verbal and
      sexual abuse, forced drinking; and forced sex more than once. The majority (90%)
      reported at least one type of harm, 38% received harm protection from 'mommies'
      (i.e., managers) and 32% reported unprotected sex with clients. In multivariate
      models, unprotected sex was significantly associated with longer involvement in
      sex work, greater exposure to harms, and no protection from mommies. Mommies'
      protection moderated the effect of sex-work harms on unprotected sex with
      clients. Our ethnography indicated that mommies played a core role in sex-work
      networks. Such networks provide a basis for social capital; they are not only
      profitable economically, but also protect FSWs from sex-work harms. Effective HIV
      prevention interventions for FSWs in China must address the occupational safety
      and health of FSWs by facilitating social capital and protection agency (e.g.,
      mommies) in the sex-work industry.

PMID- 22375699
TI  - Changes in HIV risk behavior and seroincidence among clients presenting for
      repeat HIV counseling and testing in Moshi, Tanzania.
AB  - While HIV counseling and testing (HCT) has been considered an HIV preventive
      measure in Africa, data are limited describing behavior changes following HCT.
      This study evaluated behavior changes and estimated HIV seroincidence rate among
      returning HCT clients. Repeat and one-time testing clients receiving HCT services
      in Moshi, Tanzania were identified. Information about sociodemographic
      characteristics, HIV-related behaviors and testing reasons were collected, along
      with HIV serostatus. Six thousand seven hundred and twenty-seven clients
      presented at least once for HCT; 1235 (18.4%) were HIV seropositive, median age
      was 29.7 years and 3712 (55.3%) were women. 1382 repeat and 4272 one-time testers
      were identified. Repeat testers were more likely to be male, older, married, or
      widowed, and testing because of unfaithful partner or new sexual partner. One
      time testers were more likely to be students and testing due to illness. At
      second test, repeat testers were more likely to report that partners had received
      HIV testing, not have concurrent partners, not suspect partners have HIV, and
      have partners who did not have other partners. Clients who intended to change
      behaviors after the first test were more likely to report having changed
      behaviors by remaining abstinent (OR 2.58; p<0.0001) or using condoms (OR 2.00;
      p=0.006) at the second test. HIV seroincidence rate was 1.49 cases/100 person
      years (PY). Clients presenting for repeat HCT reported some reduction of risky
      behavior and improved knowledge of sexual practices and HIV serostatus of their
      partners. Promoting behavior change through HCT should continue to be a focus of
      HIV prevention efforts in sub-Saharan Africa.

PMID- 22375700
TI  - Equity in development and access to health services in the Wild Coast of South
      Africa: the community view through four linked cross-sectional studies between
      1997 and 2007.
AB  - BACKGROUND: After election in 1994, the South African government implemented
      national and regional programmes, such as the Wild Coast Spatial Development
      Initiative (SDI), to provoke economic growth and to decrease inequities. CIET
      measured development in the Wild Coast region across four linked cross-sectional
      surveys (1997-2007). The 2007 survey was an opportunity to look at inequities
      since the original 1997 baseline, and how such inequities affect access to health
      care. METHODS: The 2000, 2004 and 2007 follow-up surveys revisited the
      communities of the 1997 baseline. Household-level multivariate analysis looked at
      development indicators and access to health in the context of inequities such as
      household crowding, access to protected sources of water, house roof
      construction, main food item purchased, and perception of community empowerment.
      Individual multivariate models accounted for age, sex, education and income
      earning opportunities. RESULTS: Overall access to protected sources of water
      increased since the baseline (from 20% in 1997 to 50% in 2007), yet households
      made of mud and grass, and households who bought basics as their main food item
      were still less likely to have protected sources of water. The most vulnerable,
      such as those with less education and less water and food security, were also
      less likely to have worked for wages leaving them with little chance of improving
      their standard of living (less education OR 0.59, 95%CI 0.37-0.94; less water
      security OR 0.67, 95%CI 0.48-0.93; less food security OR 0.43, 95%CI 0.29-0.64).
      People with less income were more likely to visit government services (among men
      OR 0.28, 95%CI 0.13-0.59; among women OR 0.33, 95%CI 0.20-0.54), reporting
      decision factors of cost and distance; users of private clinics sought out better
      service and medication. Lower food security and poorer house construction was
      also associated with women visiting government rather than private health
      services. Women with some formal education were nearly eight times more likely
      than women with no education to access health services for prevention rather than
      curative reasons (OR 7.65, 95%CI 4.10-14.25). CONCLUSION: While there have been
      some improvements, the Wild Coast region still falls well below provincial and
      national standards in key areas such as access to clean water and employment
      despite years of government-led investment. Inequities remain prominent,
      particularly around access to health services.

PMID- 22375701
TI  - On the role of the three-phase contact line in surface deformation.
AB  - Viscoelastic braking theories developed by Shanahan and de Gennes and by others
      predict deformation of a solid surface at the solid-liquid-air contact line. This
      phenomenon has only been observed for soft smooth surfaces and results in a
      protrusion of the solid surface at the three-phase contact line, in agreement
      with the theoretical predictions. Despite the large (enough to break chemical
      bonds) forces associated with it, this deformation was not confirmed
      experimentally for hard surfaces, especially for hydrophobic ones. In this study
      we use superhydrophobic surfaces composed of an array of silicon nanostructures
      whose Young modulus is 4 orders of magnitude higher than that of surfaces in
      earlier recorded viscoelastic braking experiments. We distinguish between two
      cases: when a water drop forms an adhesive contact, albeit small, with the
      apparent contact angle theta < 180 degrees  and when the drop-surface adhesion is
      such that the conditions for placing a resting drop on the surface cannot be
      reached (i.e., theta = 180 degrees ). In the first case we show that there is a
      surface deformation at the three-phase contact line which is associated with a
      reduction in the hydrophobicity of the surface. For the second case, however,
      there cannot be a three-phase contact line associated with a drop in contact with
      the surface, and indeed, if we force-place a drop on the surface by holding it
      with a needle, no deformation is detected, nor is there a reduction in the
      hydrophobic properties of the surface. Yet, if we create a long horizontal three
      phase contact line by partially immersing the superhydrophobic substrate in a
      water bath, we see a localized reduction in the hydrophobic properties of the
      surface in the region where the three-phase contact line used to be. The SEM scan
      of that region shows a narrow horizontal stripe where the nanorods are no longer
      there, and instead there is only a shallow structure that is lower than the
      nanorods height and resembles fused or removed nanorods. Away from that region,
      either on the part of the surface which was exposed to bulk water or the part
      which was exposed to air, no change in the hydrophobic properties of the surface
      is observed, and the SEM scan confirms that the nanorods seem intact in both
      regions.

PMID- 22375702
TI  - A homologue of the human STRIPAK complex controls sexual development in fungi.
AB  - Sexual development in fungi is a complex process involving the generation of new
      cell types and tissues - an essential step for all eukaryotic life. The
      characterization of sterile mutants in the ascomycete Sordaria macrospora has led
      to a number of proteins involved in sexual development, but a link between these
      proteins is still missing. Using a combined tandem-affinity purification/mass
      spectrometry approach, we showed in vivo association of developmental protein
      PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding
      subunit of protein phosphatase 2A. Further experiments extended the protein
      network to the putative kinase activator SmMOB3, known to be involved in sexual
      development. Extensive yeast two-hybrid studies allowed us to pinpoint functional
      domains involved in protein-protein interaction. We show for the first time that
      a number of already known factors together with new components associate in vivo
      to form a highly conserved multi-subunit complex. Strikingly, a similar complex
      has been described in humans, but the function of this so-called striatin
      interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S.
      macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual
      development and cell fusion, indicating a role for the fungal STRIPAK complex in
      both processes.

PMID- 22375704
TI  - Magnetic and neutron diffraction study on melilite-type oxides Sr2MGe2O7 (M = Mn,
      Co).
AB  - The crystal structures and magnetic properties of melilite-type oxides
      Sr(2)MGe(2)O(7) (M = Mn, Co) were investigated. These compounds crystallize in
      the melilite structure with space group P 42(1)m, in which the M and Ge ions
      occupy two kinds of tetrahedral sites in an ordered manner. The magnetic M ions
      form a square-planar lattice in the ab plane. Both compounds do not show the
      structural phase transition down to 2.5 K. The temperature dependence of magnetic
      susceptibility for Sr(2)MnGe(2)O(7) shows a broad peak at ~6.0 K because of a two
      dimensional magnetic interaction between Mn ions in the ab plane. At 4.4 K, an
      antiferromagnetic transition was observed. The magnetic structure was determined
      by the neutron powder diffraction measurements at 2.5 K. It can be represented by
      the propagation vector k = (0, 0, 1/2), and the magnetic moments of Mn(2+) (3.99
      MU(B)) ions order antiferromagnetically in a collinear manner along the c axis.
      On the other hand, Sr(2)CoGe(2)O(7) shows an antiferromagnetic transition at 6.5
      K with divergence between zero-field-cooled and field-cooled susceptibilities.
      Its magnetic structure determined at 2.5 K has a magnetic propagation vector k =
      (0, 0, 0), and the ordered magnetic moment of Co(2+) (2.81 MU(B)) adopts a
      collinear arrangement lying on the ab plane.

PMID- 22375705
TI  - Urinary steroid profile in early pregnancy after in vitro fertilization.
AB  - OBJECTIVE: The aim of the study was to compare the levels of urinary steroid
      metabolites of patients with successful in vitro fertilization and patients who
      failed to achieve pregnancy. DESIGN: Comparison of urinary steroid profiles prior
      to oocyte pick-up and three weeks after embryo transfer. SETTING: University
      hospital. SAMPLE: Eleven women in the same age range with pregnancy after in
      vitro fertilization and eleven women who failed to achieve pregnancy. METHODS:
      The standard "long" protocol was used for ovarian stimulation and
      intracytoplasmic sperm injection for assisted in vitro fertilization. The steroid
      metabolites in urine samples collected for 24 h were determined by gas
      chromatography-mass spectrometry. MAIN OUTCOME MEASURES: Steroid metabolite
      levels in urine samples determined in the early pregnancy period. RESULTS: The
      levels of androsterone, etiocholanolone, pregnanediol, tetrahydro-11
      dehydrocorticosterone and tetrahydro-corticosterone were significantly higher (p
      < 0.05) in the urine of women with successful pregnancy three weeks after the
      embryo transfer, while the levels of tetrahydrocortisone, tetrahydrocortisol,
      allo-tetrahydrocortisol and alpha-cortolone became higher in the group of
      patients with unsuccessful pregnancy. CONCLUSIONS: The production of androgens,
      progesterone and corticoid steroid metabolites is altered in the early pregnancy
      period after in vitro fertilization.

PMID- 22375707
TI  - Design, recombinant expression and convenient A-chain N-terminal europium
      labelling of a fully active human relaxin-3 analogue.
AB  - Relaxin-3 (also known as INSL7) is a recently identified neuropeptide belonging
      to the insulin/relaxin superfamily. It plays a putative role in the regulation of
      food intake, in the stress response and in reproduction by activating the G
      protein-coupled receptor, RXFP3. In a previous study, we prepared 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)/Eu(3+)-labelled human
      relaxin-3 as a tracer for the study of ligand-receptor interactions, which
      necessitated a complicated site-specific labelling strategy because human relaxin
      3 contains four primary amine moieties, all of which react with the primary amine
      specific modification reagent. To simplify the labelling procedure, in the
      present study we created an easily labelled, recombinant analogue of human
      relaxin-3 with only one primary amine moiety at the A-chain N-terminus. The
      analogue retained full activity and could be easily labelled by various
      functional probes at the A-chain N-terminus. The DOTA/Eu(3+)-labelled analogue
      retained high binding affinity for its cognate receptor, RXFP3, and thus
      represents a useful, nonradioactive and stable tracer for studying the
      interaction of RXFP3 with various natural or synthetic ligands. This new analogue
      is also a suitable template for the design of other relaxin-3 analogues that can
      be easily labelled with the DOTA/Eu(3+) moiety and used to study binding activity
      and interactions with various RXFP3 analogues in the future.

PMID- 22375708
TI  - Feminizing Wolbachia: a transcriptomics approach with insights on the immune
      response genes in Armadillidium vulgare.
AB  - BACKGROUND: Wolbachia are vertically transmitted bacteria known to be the most
      widespread endosymbiont in arthropods. They induce various alterations of the
      reproduction of their host, including feminization of genetic males in isopod
      crustaceans. In the pill bug Armadillidium vulgare, the presence of Wolbachia is
      also associated with detrimental effects on host fertility and lifespan.
      Deleterious effects have been demonstrated on hemocyte density, phenoloxidase
      activity, and natural hemolymph septicemia, suggesting that infected individuals
      could have defective immune capacities. Since nothing is known about the
      molecular mechanisms involved in Wolbachia-A. vulgare interactions and its
      secondary immunocompetence modulation, we developed a transcriptomics strategy
      and compared A. vulgare gene expression between Wolbachia-infected animals (i.e.,
      "symbiotic" animals) and uninfected ones (i.e., "asymbiotic" animals) as well as
      between animals challenged or not challenged by a pathogenic bacteria. RESULTS:
      Since very little genetic data is available on A. vulgare, we produced several
      EST libraries and generated a total of 28 606 ESTs. Analyses of these ESTs
      revealed that immune processes were over-represented in most experimental
      conditions (responses to a symbiont and to a pathogen). Considering canonical
      crustacean immune pathways, these genes encode antimicrobial peptides or are
      involved in pathogen recognition, detoxification, and autophagy. By RT-qPCR, we
      demonstrated a general trend towards gene under-expression in symbiotic whole
      animals and ovaries whereas the same gene set tends to be over-expressed in
      symbiotic immune tissues. CONCLUSION: This study allowed us to generate the first
      reference transcriptome ever obtained in the Isopoda group and to identify genes
      involved in the major known crustacean immune pathways encompassing cellular and
      humoral responses. Expression of immune-related genes revealed a modulation of
      host immunity when females are infected by Wolbachia, including in ovaries, the
      crucial tissue for the Wolbachia route of transmission.

PMID- 22375709
TI  - Pseudomonas fluorescens induces strain-dependent and strain-independent host
      plant responses in defense networks, primary metabolism, photosynthesis, and
      fitness.
AB  - Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can
      confer enhanced defense capacity against a broad spectrum of pathogens. Few
      studies, however, have linked defense pathway regulation to primary metabolism
      and physiology. In this study, physiological data, metabolites, and transcript
      profiles are integrated to elucidate how molecular networks initiated at the root
      microbe interface influence shoot metabolism and whole-plant performance.
      Experiments with Arabidopsis thaliana were performed using the newly identified
      P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks
      indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for
      genes participating in RNA regulation, protein degradation, and hormonal
      metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium
      signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain
      dependence in network architecture. In addition, one subnetwork present in shoots
      was enriched for genes in secondary metabolism, photosynthetic light reactions,
      and hormone metabolism. Metabolite analysis indicated that this network initiated
      changes in carbohydrate and amino acid metabolism. Consistent with this, we
      observed strain-specific responses in tryptophan and phenylalanine abundance.
      Both strains reduced host plant carbon gain and fitness, yet provided a clear
      fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

PMID- 22375710
TI  - Cucumis melo microRNA expression profile during aphid herbivory in a resistant
      and susceptible interaction.
AB  - Aphis gossypii resistance in melon (Cucumis melo) is due to the presence of a
      single dominant virus aphid transmission (Vat) gene belonging to the nucleotide
      binding site leucine-rich repeat family of resistance genes. Significant
      transcriptional reprogramming occurs in Vat(+) plants during aphid infestation as
      metabolism shifts to respond to this biotic stress. MicroRNAs (miRNAs) are
      involved in the regulation of many biotic stress responses. The role of miRNAs
      was investigated in response to aphid herbivory during both resistant and
      susceptible interactions. Small RNA (smRNA) libraries were constructed from
      bulked leaf tissues of a Vat(+) melon line following early and late aphid
      infestations. Sequence analysis indicated that the expression profiles of
      conserved and newly identified miRNAs were altered during different stages of
      aphid herbivory. These results were verified by quantitative polymerase chain
      reaction experiments in both resistant Vat(+) and susceptible Vat(-)
      interactions. The comparative analyses revealed that most of the conserved miRNA
      families were differentially regulated during the early stages of aphid
      infestation in the resistant and susceptible interactions. Along with the
      conserved miRNA families, 18 cucurbit-specific miRNAs were expressed during the
      different stages of aphid herbivory. The comparison of the miRNA profiles in the
      resistant and susceptible interactions provides insight into the miRNA-dependent
      post-transcriptional gene regulation in Vat-mediated resistance.

PMID- 22375712
TI  - High aspect subdiffraction-limit photolithography via a silver superlens.
AB  - Photolithography is the technology of choice for mass patterning in semiconductor
      and data storage industries. Superlenses have demonstrated the capability of
      subdiffraction-limit imaging and been envisioned as a promising technology for
      potential nanophotolithography. Unfortunately, subdiffraction-limit patterns
      generated by current superlenses exhibited poor profile depth far below the
      requirement for photolithography. Here, we report an experimental demonstration
      of sub-50 nm resolution nanophotolithography via a smooth silver superlens with a
      high aspect profile of ~45 nm, as well as grayscale subdiffraction-limit three
      dimensional nanopatterning. Theoretical analysis and simulation show that smooth
      interfaces play a critical role. Superlens-based lithography can be integrated
      with conventional UV photolithography systems to endow them with the capability
      of nanophotolithography, which could provide a cost-effective approach for large
      scale and rapid nanopatterning.

PMID- 22375711
TI  - Fully covered self-expandable metal stents (SEMS), partially covered SEMS and
      self-expandable plastic stents for the treatment of benign esophageal ruptures
      and anastomotic leaks.
AB  - BACKGROUND: Benign esophageal ruptures and anastomotic leaks are life-threatening
      conditions that are often treated surgically. Recently, placement of partially
      and fully covered metal or plastic stents has emerged as a minimally invasive
      treatment option. We aimed to determine the clinical effectiveness of covered
      stent placement for the treatment of esophageal ruptures and anastomotic leaks
      with special emphasis on different stent designs. METHODS: Consecutive patients
      who underwent placement of a fully covered self-expandable metal stent (FSEMS), a
      partially covered SEMS (PSEMS) or a self-expanding plastic stent (SEPS) for a
      benign esophageal rupture or anastomotic leak after upper gastrointestinal
      surgery in the period 2007-2010 were included. Data on patient demographics, type
      of lesion, stent placement and removal, clinical success and complications were
      collected RESULTS: A total of 52 patients received 83 esophageal stents (61
      PSEMS, 15 FSEMS, 7 SEPS) for an anastomotic leak (n=32), iatrogenic rupture
      (n=13), Boerhaave's syndrome (n=4) or other cause (n=3). Endoscopic stent removal
      was successful in all but eight patients treated with a PSEMS due to tissue
      ingrowth. Clinical success was achieved in 34 (76%, intention-to-treat: 65%)
      patients (PSEMS: 73%, FSEMS: 83%, SEPS: 83%) after a median of 1 (range 1-5)
      stent and a median stenting time of 39 (range 7-120) days. In total, 33
      complications in 24 (46%) patients occurred (tissue in- or overgrowth (n=8),
      stent migration (n=10), ruptured stent cover (all Ultraflex; n=6), food
      obstruction (n=3), severe pain (n=2), esophageal rupture (n=2), hemorrhage
      (n=2)). One (2%) patient died of a stent-related cause. CONCLUSIONS: Covered
      stents placed for a period of 5-6 weeks may well be an alternative to surgery for
      treating benign esophageal ruptures or anastomotic leaks. As efficacy between
      PSEMS, FSEMS and SEPS is not different, stent choice should depend on expected
      risks of stent migration (SEPS and FSEMS) and tissue in- or overgrowth (PSEMS).

PMID- 22375713
TI  - Height: a universal cancer risk factor?

PMID- 22375714
TI  - Is preoperative staging with breast MRI causing overtreatment with mastectomies?

PMID- 22375716
TI  - BRCA1 haploinsufficiency: consequences for breast cancer.
AB  - In their study, Konishi et al. generate and study cell lines that carry one
      mutant and one normal copy of BRCA1. These heterozygous (noncancerous) cells are
      noteworthy in that they carry an increased number of copy number alterations and
      have diminished DNA repair capacity. These observations go beyond the classical
      two-hit hypothesis for inherited cancers, whereby the cell phenotype is normal
      until the second allele is lost through somatic mutation or epigenetic silencing.
      They propose that BRCA1 heterozygosity is associated with increased genomic
      instability, which accelerates the mutation rate of other critical genes,
      including the second copy of BRCA1. They conclude that BRCA1 is a
      haploinsufficient tumor suppressor gene, which when lost through inheritance,
      increases a cell's susceptibility to acquire further mutations.

PMID- 22375717
TI  - Management of noncardiac chest pain in women.
AB  - Noncardiac chest pain (NCCP) is very prevalent in the community. Although
      mortality remains low, morbidity and the financial implications are high. Women,
      especially those of middle age, should be thoroughly investigated as per current
      guidelines for coronary artery disease before labeling their chest pain as NCCP.
      Gastroesophageal reflux disease is the most common cause of NCCP; however other
      esophageal pathology including esophageal hypersensitivity, neuromuscular disease
      and eosinophilic esophagitis may also cause NCCP. Proton pump inhibitors are
      commonly used initially to manage NCCP, although patients who do not respond to
      this therapy require further investigation and differing treatment regimes. This
      article will focus on current knowledge regarding GI tract-related NCCP
      management strategies.

PMID- 22375718
TI  - The link between polycystic ovary syndrome and both Type 1 and Type 2 diabetes
      mellitus: what do we know today?
AB  - Polycystic ovary syndrome (PCOS) and Type 2 diabetes mellitus (T2D) are both
      obesity-related conditions that share epidemiological and pathophysiological
      factors. Insulin resistance is a key factor whereby obesity influences the
      expression of each condition. However, the mechanisms by which insulin resistance
      contributes towards the manifestation of PCOS and T2D differ in important ways:
      in PCOS, compensatory hyperinsulinemia results in pleiotropic effects including
      co-gonadotrophic stimulation of ovarian and adrenal steroidogenesis; in T2D,
      insulin resistance contributes towards beta-cell exhaustion and ultimately to
      hyposecretion of insulin with resultant dysglycemia. The link between PCOS and
      Type 1 diabetes mellitus is believed to implicate supraphysiological
      concentrations of insulin within the systemic circulation. Further progression of
      the obesity epidemic will ensure even greater prominence of important obesity
      related conditions such as PCOS and T2D. Research to gain a clearer understanding
      of the mechanisms linking each condition should be a priority.

PMID- 22375719
TI  - Does menopause increase diabetes risk? Strategies for diabetes prevention in
      midlife women.
AB  - Menopause is a significant milestone for midlife women. The characteristic
      changes in sex hormones and associated symptoms mark a time of increased risk for
      chronic disease, most notably cardiovascular disease. The diabetes epidemic,
      combined with recent epidemiologic studies linking sex hormone profiles with
      incident diabetes risk, have recently raised the possibility that the menopause
      may increase diabetes risk as well. This report reviews studies of menopause and
      diabetes risk, as well as the potential mechanisms through which menopause might
      affect traditional and more novel diabetes risk factors. Diabetes risk appears to
      be more strongly linked with factors associated with chronological aging and sex
      hormones rather than changes in menopausal status per se. Strategies to reduce
      diabetes risk, namely lifestyle changes, hormone therapy and other pharmacologic
      interventions are also discussed vis a vis midlife women and menopause.

PMID- 22375720
TI  - Update: estrogen and estrogen plus progestin therapy in the care of women at and
      after the menopause.
AB  - Much new information on menopausal hormone therapy (MHT) has become available
      since the publication of the first report of the Women's Health Initiative in
      2002 and a consensus is now emerging. The risk of breast cancer depends on type
      of MHT, duration of use, body mass, breast density and interval between menopause
      and starting MHT. The risk of breast cancer is generally increased by MHT,
      particularly in lean women with no previous MHT who start estrogen-progestin
      therapy near the menopause and continue for several years, but there is no
      increased risk 5 years after stopping MHT. The risks of venous thrombo-embolic
      disease (VTE), stroke and coronary heart disease (CHD) depend on age on starting
      MHT, dose, nature and route of administration of MHT. The risk of VTE is
      increased in women over 60 years of age and in women who are obese or have had a
      VTE but may not be increased by transdermal estrogens. The risk of stroke is very
      small in women under 60 years of age and may not be increased by low dose oral
      and low dose transdermal estrogen. MHT is of benefit in preventing
      atherosclerosis and CHD in healthy younger postmenopausal women (under the age of
      60) but is not of benefit, and may be harmful, in older women with clinical or
      subclinical atherosclerosis. MHT prevents bone loss and osteoporosis but is not
      generally recommended in women over 60 because of the risks of VTE, stroke and
      CHD, and if stopped at 60 years does not prevent fractures in later life. MHT
      reduces the overall mortality in women under 60. MHT is by far the most effective
      treatment, and greatly improves the quality of life in women with menopausal
      symptoms. A simplified approach to MHT is suggested as a framework for the care
      of women at and after the menopause.

PMID- 22375721
TI  - Impact of FDG-PET and -PET/CT imaging in the clinical decision-making of ovarian
      carcinoma: an evidence-based approach.
AB  - The most definitive role of fluorodeoxyglucose (FDG)-PET/computed tomography (CT)
      at present is surveillance and detecting recurrence in patients who have
      completed primary therapy but demonstrate a rising serum tumor marker (e.g., CA
      125 levels). In this scenario, PET/CT demonstrates high sensitivity and accuracy
      in detecting lesions that are otherwise challenging, and appears superior (with
      less interobserver variability) compared with CT alone. Despite the fact that
      peritoneal deposits may be missed by PET/CT, the overall performance is better
      than CT alone. FDG-PET does not play a significant additional role in the primary
      diagnosis of ovarian cancers; however, the role of combined PET/CT modality has
      recently begun to be re-explored for initial disease staging, particularly
      because PET/CT can pick up small unsuspected lesions and thereby provide a better
      disease assessment of the whole body in a single examination. The baseline PET/CT
      also subserves an important role for future monitoring of therapy response.
      Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols
      and to avoid ineffective therapy in nonresponders early in its course, although
      PET/CT has cost-effectiveness issues that need further evaluation. The prognostic
      value of FDG-PET/CT has been investigated in the following areas: in the
      preoperative setting to predict optimal cytoreduction; to assess the value of a
      positive FDG-PET following primary surgery; and when employed as a replacement
      for second-look laparotomy following completion of primary surgery and
      chemotherapy. The data, although promising, are still sparse in all the three
      domains for a definite recommendation.

PMID- 22375722
TI  - Easing maternal anxiety: an update.
AB  - Maternal mental health is an important public health issue because of its effects
      not only on the mother's well-being and functional status, but also her
      relationship with her partner and the development of her children. There is
      accumulating evidence of the adverse sequelae of maternal anxiety on fetal
      development, obstetrical complications, pregnancy outcomes such as low birth
      weight, and subsequent child development. Evaluation of maternal anxiety and
      intervention to reduce these symptoms, may ensure optimal developmental outcomes,
      particularly in high-risk infants such as those born at very low birth weights.
      This article will outline recent advances in our understanding of the etiology,
      assessment and impact of maternal anxiety, and describe intervention strategies
      to promote maternal well-being.

PMID- 22375723
TI  - Women and psychosis.
AB  - BACKGROUND: There are subtle differences in the presentation of psychosis that
      depend on the biological sex of the person exhibiting the symptoms. Because much
      of the early research in the field was conducted on male animals and on men,
      several issues of importance to women have been relatively neglected until
      recently. Current research into psychotic illness is beginning to analyze results
      for men and women separately and greater emphasis on qualitative methods has
      allowed the experiences of women patients to be documented. METHODS: The last
      decade of research into the many facets of psychosis in women were reviewed for
      this paper by introducing the relevant search terms into PubMed, PsycINFO and
      SOCINDEX. RESULTS: Subtle differences are reported in several areas, with
      important ramifications for treatment. CONCLUSIONS: It is important for service
      providers to devise treatment programs that address the different needs of the
      two sexes. Effective treatment of women with psychosis is especially important in
      that these women are often mothers, whose well being impacts on the health of the
      next generation.

PMID- 22375726
TI  - Metabolism of oak leaf ellagitannins and urolithin production in beef cattle.
AB  - Oak leaves have a high concentration of ellagitannins. These phytochemicals can
      be beneficial or poisonous to animals. Beef cattle are often intoxicated by oak
      leaf consumption, particularly after suffering feed restriction. The severity of
      the poisoning has recently been associated with the ruminal microbiota, as
      different bacterial populations were found in animals that tolerated oak leaves
      and in those that showed clinical and pathological signs of toxicity.
      Intoxication has previously been linked to the production of phenolic
      metabolites, particularly catechol, phloroglucinol, and resorcinol. This
      suggested that the microbial metabolism of ellagitannins could also be associated
      with its tolerance or intoxication in different animals. Therefore, it is
      essential to understand the metabolism of ellagitannins in cattle. Here we show
      that ellagitannins are metabolized in the cattle rumen to urolithins. Different
      urolithins were detected in ruminal fluid, feces, urine, and plasma. Oak leaf
      ellagitannins declined as they were converted to urolithins, mainly isourolithin
      A and urolithin B, by the ruminal and fecal microbiota. Urolithin aglycons were
      observed in rumen and feces, and glucuronide and sulfate derivatives were
      detected in plasma and urine. Sulfate derivatives were the main metabolites
      detected in plasma, while glucuronide derivatives were the main ones in urine.
      The main urolithins produced in cattle were isourolithin A and urolithin B. This
      is a relevant difference from the monogastric mammals studied previously in which
      urolithin A was the main metabolite produced. Low molecular weight phenolics of
      the benzoic, phenylacetic, and phenylpropionic groups and metabolites such as
      catechol, resorcinol, and related compounds were also detected. There was a large
      variability in the kinetics of production of these metabolites in individual
      animals, although they produced similar metabolites in all cases. This large
      variability could be associated with the large variability in the rumen and
      intestine microbiota that has previously been observed. Further studies are
      needed to demonstrate if the efficiency in the metabolism of ellagitannins by the
      microbiota could explain the differences observed in susceptibility to
      intoxication by the different animals.

PMID- 22375727
TI  - Attention-deficit/hyperactivity disorder with oppositional defiant disorder in
      Swedish children - an open study of collaborative problem solving.
AB  - AIM: To evaluate collaborative problem solving (CPS) in Swedish 6-13-year-old
      children with attention-deficit/hyperactivity disorder and oppositional defiant
      disorder (ODD). METHODS: Seventeen families completed 6-10 sessions of CPS
      training. Primary outcome measures were SNAP-IV [attention-deficit/hyperactivity
      disorder (ADHD) and ODD scores] and Clinical Global Impression-Improvement (CGI
      I) scores at baseline, post-intervention and 6 months later. Secondary outcome
      measures were the Conners' 10-item scale and the Family Burden of Illness Module
      (FBIM). RESULTS: All 17 participants completed the intervention. The whole group
      had significant reductions in SNAP-IV ODD, ADHD, total Conners' and FBIM scores,
      both at post-intervention and at 6-month follow-up. Eight of the children,
      although significantly improved on ODD scores and the Conners' emotional lability
      subscale at post-intervention, had almost no improvement in
      hyperactivity/impulsivity. Post-intervention, this group received stimulant
      medication for their ADHD. CGI-I scores of much improved or very much improved
      were reached by 53% (9/17) of all at post-intervention, and by 81% (13/16) at 6
      month follow-up. CONCLUSION: Collaborative problem solving significantly reduced
      ODD, ADHD and emotional lability symptoms. A subgroup improved in their ADHD
      symptoms only after adding stimulant medication.

PMID- 22375728
TI  - Effects of ethynyl substituents on the electronic structure of cyclobutadiene.
AB  - The effects of ethynyl substitution on the electronic structure of cyclobutadiene
      are investigated in this work. Ethynyl substituted cyclobutadienes may be
      involved in Bergman cyclization reactions and are possible intermediates in the
      formation of fullerenes and graphitic sheets. Prediction of the electronic
      structure of cyclobutadiene is challenging for single-reference ab initio methods
      because of Jahn-Teller distortions and the diradical character of the singlet
      state. The equation-of-motion spin-flip coupled-cluster with single and double
      excitations (EOM-SF-CCSD) method accurately describes diradical states and is
      used to determine vertical and adiabatic singlet-triplet energy splittings in the
      substituted cyclobutadienes. The adiabatic singlet-triplet gaps decrease upon
      substituent addition, but the singlet states remain lower in energy. However, the
      results are affected by spin-contamination of the reference state and deteriorate
      when an unrestricted HF reference is employed. Additional insights in the
      electronic structure of cyclobutadienes are obtained by analyzing natural charges
      and spin densities. The substituents pull the charge out of the cyclobutadiene
      ring; however, the natural charges and spin densities are found to be nearly
      independent of the geometry and spin state.

PMID- 22375730
TI  - Update on the genetics of migraine.

PMID- 22375729
TI  - Sexual agreements in the partnerships of internet-using men who have sex with
      men.
AB  - Recent studies among men who have sex with men (MSM) have found that the majority
      of HIV transmission results from sex with a main partner. One factor likely to
      affect the risk of transmission is the type of agreements the couple has
      regarding sexual behaviour within and outside the relationship. This study
      recruited 732 Internet-using MSM through Facebook banner ads. Participants
      completed an online questionnaire regarding demographic characteristics of the
      respondent and their main partner, the sexual behaviour of the couple, the
      existence of a sexual agreement, and the strength of investment in that
      agreement. The Pearson chi-square test was used to assess the association between
      sexual agreements (categorized as open, closed, or none) and the predictive
      variables. Respondents' investment in their sexual agreement was measured using
      the sexual agreement investment scale (a composite score ranging from 0 to 52).
      Ninety-one percent of respondents had some form of sexual agreement in place with
      their main partner. The presence and type of sexual agreement was found to be
      strongly associated with many characteristics of the individual and couple,
      including the respondent's HIV status, length of time with the main partner,
      having unprotected anal intercourse with a man other than their main partner, and
      happiness in the relationship. Increases in the strength of respondents'
      investment in their sexual agreement were found to be associated with newness of
      the relationship, relationship happiness, having a closed relationship, and
      decreases in risky sexual behaviour. This study offers further evidence of the
      important role that sexual agreements play in male couples. The overwhelming
      prevalence of sexual agreements and their association with relationship happiness
      and risky sexual behaviours has important implications for future HIV prevention
      and control strategies, including the implementation of couples voluntary
      counseling and testing.

PMID- 22375732
TI  - Nature and role of change in anxiety sensitivity during NRT-aided cognitive
      behavioral smoking cessation treatment.
AB  - This study evaluated the associations between change in anxiety sensitivity (AS;
      fear of the negative consequences of anxiety and related sensations) and lapse
      and relapse during a 4-week group NRT-aided cognitive-behavioral Tobacco
      Intervention Program. Participants were 67 (44 women; M (age) = 46.2 years, SD =
      10.4) adult daily smokers. Results indicated that participants who maintained
      high levels of AS from pretreatment to 1 month posttreatment, compared to those
      who demonstrated a significant reduction in AS levels during this time period,
      showed a significantly increased risk for lapse and relapse. Further inspection
      indicated that higher continuous levels of AS physical and psychological
      concerns, specifically among those participants who maintained elevated levels of
      AS from pre- to posttreatment, predicted significantly greater risk for relapse.
      Findings are discussed with respect to better understanding change in AS,
      grounded in an emergent taxonic-dimensional factor mixture model of the
      construct, with respect to lapse and relapse during smoking cessation.

PMID- 22375731
TI  - Relationship between reported prior condom use and current self-perceived risk of
      acquiring HIV among mobile female sex workers in southern India.
AB  - BACKGROUND: With the evolution of Health Belief Model, risk perception has been
      identified as one of several core components of public health interventions.
      While female sex workers (FSWs) in India continue to be at most risk of acquiring
      and transmitting HIV, little is known about their perception towards risk of
      acquiring HIV and how this perception depends upon their history of consistent
      condom use behavior with different type of partners. The objective of this study
      is to fill this gap in the literature by examining this relationship among mobile
      FSWs in southern India. METHODS: We analyzed data for 5,413 mobile FSWs from a
      cross-sectional behavioral survey conducted in 22 districts from four states in
      southern India. This survey assessed participants' demographics, condom use in
      sex with different types of partners, continuation of sex while experiencing STI
      symptoms, alcohol use before having sex, and self-perceived risk of acquiring
      HIV. Descriptive analyses and multilevel logistic regression models were used to
      examine the associations between risky sexual behaviors and self-perceived risk
      of acquiring HIV; and to understand the geographical differences in HIV risk
      perception. RESULTS: Of the total mobile FSWs, only two-fifths (40%) perceived
      themselves to be at high risk of acquiring HIV; more so in the state of Andhra
      Pradesh (56%) and less in Maharashtra (17%). FSWs seem to assess their current
      risk of acquiring HIV primarily on the basis of their past condom use behavior
      with occasional clients and less on the basis of their past condom use behaviors
      with regular clients and non-paying partners. Prior inconsistent condom use with
      occasional clients was independently associated with current perception of high
      HIV risk (adjusted odds ratio [aOR)] = 2.1, 95% confidence interval [CI]: 1.7
      2.6). In contrast, prior inconsistent condom use with non-paying partners was
      associated with current perception of low HIV risk (aOR= 0.7, 95% CI: 0.5-0.9).
      The congruence between HIV risk perception and condom use with occasional clients
      was high: only 12% of FSWs reported inconsistent condom use with occasional
      clients but perceived themselves to be at low risk of acquiring HIV. CONCLUSION:
      The association between high risk perception of acquiring HIV and inconsistent
      condom use, especially with regular clients and non-paying partners, has not been
      completely internalized by this high risk group of mobile FSWs in India.
      Motivational efforts to prevent HIV should emphasize the importance of accurately
      assessing an individual's risk of acquiring HIV based on condom use behavior with
      all types of partners: occasional and regular clients as well as non-paying
      partners; and encourage behavior change based on an accurate self-assessment of
      HIV risk.

PMID- 22375733
TI  - Exploration of a factor mixture-based taxonic-dimensional model of anxiety
      sensitivity and transdiagnostic psychopathology vulnerability among trauma
      exposed adults.
AB  - The aim of this study was to evaluate the associations between a factor mixture
      based taxonic-dimensional model of anxiety sensitivity (AS) and posttraumatic
      stress, panic, generalized anxiety, depression, psychiatric multimorbidity, and
      quality of life among a young adult sample exposed to traumatic stress (N = 103,
      n (females) = 66, M (age) = 23.68 years, SD (age) = 9.55). Findings showed
      support for the conceptual and operational utility of the AS taxonic-dimensional
      model with respect to concurrent transdiagnostic vulnerability among trauma
      exposed adults. Specifically, relative to the low-AS group, the high-AS group
      demonstrated elevated levels of panic, depressive, and posttraumatic stress
      symptom severity as well as greater psychiatric multimorbidity and poorer quality
      of life. Furthermore, past-month MDD, GAD, PTSD, and panic attacks occurred
      nearly exclusively among the high-AS group. Continuous AS physical and
      psychological concerns scores were found to be significantly related to levels of
      panic and posttraumatic stress symptom severity, psychiatric multimorbidity as
      well as panic attack status only among the high-AS group and not among the low-AS
      group. Findings are discussed with respect to their implications for the
      conceptual and operational utility of the FMM-based taxonic-dimensional model of
      AS, related vulnerability for psychopathology in the context of trauma, and the
      clinical implications of these findings for assessment and intervention.

PMID- 22375736
TI  - Assistive devices utilisation in activities of everyday life--a proposed
      framework of understanding a user perspective.
AB  - PURPOSE: This theoretical article proposes a framework of understanding a user
      perspective of assistive devices utilisation in everyday life. METHOD: Utilising
      the MPT model (Matching Person and Technology) and the ValMO model (Values and
      Meaning in Human Occupations), a framework of understanding is proposed. RESULTS:
      Main components are person, assistive device, and activity, connected by the
      person's expectations and experiences concerning the doability/doworthiness
      (possible to do/worth doing) of an activity, and the usability/useworthiness
      (possible to use/worth using) of an assistive device. Expectations may differ
      based on not only earlier experiences (habitus), but also situational and
      environmental variations, and result in differing experiences. In general, the
      purpose of an assistive device is to increase a person's repertoire of doable
      activities. For a person, this can be a function of the evaluation of possible
      gains, in terms of correlation between investments (in terms of time and energy),
      and the (expected) result of the activity. CONCLUSIONS: The only person able to
      estimate the useworthiness/usability of a device and the doworthiness/doability
      of an activity is the user her/himself, assessing the degree at which a specific
      assistive device enhances the value of an activity, in turn affecting the habitus
      of the (presumptive) user. [Box: see text].

PMID- 22375792
TI  - Hoechst 33342-induced autophagy protected HeLa cells from caspase-independent
      cell death with the participation of ROS.
AB  - Autophagy, an evolutionarily-conserved intracellular organelle and protein
      degradation process, may exhibit drastically different effects on cell survival
      depending on the particular environmental and culturing conditions. Hoechst 33342
      (HO), a fluorescent dye widely used for staining DNA, has been reported to induce
      apoptosis in mammalian cells. Here we showed that, in addition to caspase
      independent cell death, HO also induced autophagy in HeLa cells, as evidenced by
      the accumulation of autophagosomes, LC3 form conversion and LC3 puncta formation
      in a cell line stably expressing GFP-LC3. HO treatment led to generation of
      reactive oxygen species (ROS), and inhibition of ROS with N-acetyl-l-cysteine
      (NAC) abrogated both autophagy and caspase-independent cell death. Finally,
      autophagy played a protective role against caspase-independent cell death, as
      cell death induced by HO was enhanced under pharmacological and siRNA-mediated
      genetic inhibition of autophagy.

PMID- 22375793
TI  - The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient
      for the growth of bloodstream-form Trypanosoma brucei.
AB  - The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei.
      Phosphomannose isomerase occupies a key position on the de novo pathway to GDP
      mannose from glucose, just before intersection with the salvage pathway from free
      mannose. We identified the parasite phosphomannose isomerase gene, confirmed that
      it encodes phosphomannose isomerase activity and localized the endogenous enzyme
      to the glycosome. We also created a bloodstream-form conditional null mutant of
      phosphomannose isomerase to assess the relative roles of the de novo and salvage
      pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be
      essential for parasite growth. However, supplementation of the medium with low
      concentrations of mannose, including that found in human plasma, relieved this
      dependence. Therefore, we do not consider phosphomannose isomerase to be a viable
      drug target. We further established culture conditions where we can control
      glucose and mannose concentrations and perform steady-state [U-(13) C]-D-glucose
      labelling. Analysis of the isotopic sugar composition of the parasites variant
      surface glycoprotein synthesized in cells incubated in 5 mM [U-(13) C]-D-glucose
      in the presence and absence of unlabelled mannose showed that, under
      physiological conditions, about 80% of GDP-mannose synthesis comes from the de
      novo pathway and 20% from the salvage pathway.

PMID- 22375794
TI  - Binge alcohol-induced microvesicular liver steatosis and injury are associated
      with down-regulation of hepatic Hdac 1, 7, 9, 10, 11 and up-regulation of Hdac 3.
AB  - BACKGROUND: Binge, as well as chronic, alcohol consumption affects global histone
      acetylation leading to changes in gene expression. It is becoming increasingly
      evident that these histone-associated epigenetic modifications play an important
      role in the development of alcohol-mediated hepatic injury. METHODS: C57BL/6 mice
      were gavaged 3 times (12-hour intervals) with ethanol (EtOH; 4.5 g/kg). Hepatic
      histone deacetylase (Hdac) mRNAs were assessed by qRT-PCR. Total HDAC activity
      was estimated by a colorimetric HDAC activity/inhibition assay. Histone
      acetylation levels were evaluated by Western blot. Liver steatosis and injury
      were evaluated by histopathology, plasma aminotransferase (ALT) activity, and
      liver triglyceride accumulation. Expression of fatty acid synthase (Fas) and
      carnitine palmitoyl transferase 1a (Cpt1a) was also examined. HDAC 9 association
      with Fas promoter was analyzed. RESULTS: Binge alcohol exposure resulted in
      alterations of hepatic Hdac mRNA levels. Down-regulation of HDAC Class I (Hdac
      1), Class II (Hdac 7, 9, 10), and Class IV (Hdac 11) and up-regulation of HDAC
      Class I (Hdac 3) gene expression were observed. Correspondent to the decrease in
      HDAC activity, an increase in hepatic histone acetylation was observed. These
      molecular events were associated with microvesicular hepatic steatosis and injury
      characterized by increased hepatic triglycerides (48.02 +/- 3.83 vs. 19.90 +/-
      3.48 mg/g liver, p < 0.05) and elevated plasma ALT activity (51.98 +/- 6.91 vs.
      20.8 +/- 0.62 U/l, p < 0.05). Hepatic steatosis was associated with an increase
      in FAS and a decrease in CPT1a mRNA and protein expression. Fas promoter analysis
      revealed that binge EtOH treatment decreased HDAC 9 occupancy at the Fas promoter
      resulting in its transcriptional activation. CONCLUSIONS: Deregulation of hepatic
      Hdac expression likely plays a major role in the binge alcohol-induced hepatic
      steatosis and liver injury by affecting lipogenesis and fatty acid beta
      oxidation.

PMID- 22375795
TI  - Reproductive and sexual health in the Maldives: analysis of data from two cross
      sectional surveys.
AB  - BACKGROUND: The Maldives faces challenges in the provision of health services to
      its population scattered across many small islands. The government commissioned
      two separate reproductive health surveys, in 1999 and 2004, to inform their
      efforts to improve reproductive and sexual health services. METHODS: A stratified
      random sample of islands provided the study base for a cluster survey in 1999 and
      a follow-up of the same clusters in 2004. In 1999 the household survey enquired
      about relevant knowledge, attitudes and practices and views and experience of
      available reproductive health services, with a focus on women aged 15-49 years.
      The 2004 household survey included some of the same questions as in 1999, and
      also sought views of men aged 15-64 years. A separate survey about sexual and
      reproductive health covered 1141 unmarried youth aged 15-24 years. RESULTS: There
      were 4087 household respondents in 1999 and 4102 in 2004. The contraceptive
      prevalence rate (CPR) for modern methods was 33% in 1999 and 34% in 2004.
      Antenatal care improved: more women in 2004 than in 1999 had at least four
      antenatal care visits (90.0% v 65.1%) and took iron supplements (86.7% v 49.6%)
      during their last pregnancy. The response rate for the youth survey was only 42%
      (varying from 100% in some islands to 12% in sites in the capital). The youth
      respondents had some knowledge gaps (one third did not know if people with HIV
      could look healthy and less than half thought condoms could protect against HIV),
      and some unhelpful attitudes about gender and reproductive health. CONCLUSIONS:
      The two household surveys were commissioned as separate entities, with different
      priorities and data capture methods, rather than being undertaken as a specific
      research study. The direct comparisons we could make indicated an unchanged CPR
      and improvements in antenatal care, with the Maldives ahead of the South Asia
      region for antenatal care. The low response rate in the youth survey limited
      interpretation of the findings. But the survey highlighted areas requiring
      attention. Surveys not undertaken primarily for research purposes have important
      limitations but can provide useful information.

PMID- 22375796
TI  - Impact of deductibles on initiation and continuation of psychotherapy for
      treatment of depression.
AB  - OBJECTIVE: To estimate the impact of deductibles on the initiation and
      continuation of psychotherapy for depression. DATA SOURCES/STUDY SETTING: Data
      from health care encounters and claims from Group Health Cooperative, a large
      integrated health care system in Washington State, was merged with information
      from a centralized behavioral health triage call center to conduct study
      analyses. STUDY DESIGN: A retrospective observational design using a hierarchical
      logistic regression model was used to estimate initiation and continuation
      probabilities for use of psychotherapy, adjusting for key
      sociodemographic/economic factors and prior use of behavioral health services
      relevant to individual decisions to seek mental health care. DATA
      COLLECTION/EXTRACTION METHODS: Analyses were based on merged datasets on patient
      enrollment, insurance benefits, use of mental health and general medical services
      and information collected by a triage specialist at a centralized behavioral
      health call center. PRINCIPAL FINDINGS: Among individuals with unmet deductibles
      between $100 and $500, we found a statistically significant lower likelihood of
      making an initial visit, but there was no statistically significant effect on
      making an initial or subsequent visit among individuals that had met their
      deductible. CONCLUSIONS: Unmet deductibles appear to influence the likelihood of
      initiating psychotherapy for treating depression.

PMID- 22375798
TI  - Combined cerebral and myocardial perfusion in aortic arch reconstruction for
      pediatric patients.

PMID- 22375797
TI  - Quantitative assessment of microbicide-induced injury in the ovine vaginal
      epithelium using confocal microendoscopy.
AB  - BACKGROUND: The development of safe topical microbicides that can preserve the
      integrity of cervicovaginal tract epithelial barrier is of great interest as this
      may minimize the potential for increased susceptibility to STI infections. High
      resolution imaging to assess epithelial integrity in a noninvasive manner could
      be a valuable tool for preclinical testing of candidate topical agents. METHODS:
      A quantitative approach using confocal fluorescence microendoscopy (CFM) for
      assessment of microbicide-induced injury to the vaginal epithelium was developed.
      Sheep were treated intravaginally with one of five agents in solution (PBS; 0.02%
      benzalkonium chloride (BZK); 0.2% BZK) or gel formulation (hydroxyethyl cellulose
      (HEC); Gynol II nonoxynol-9 gel (N-9)). After 24 hours the vaginal tract was
      removed, labeled with propidium iodide (PI), imaged, then fixed for histology. An
      automated image scoring algorithm was developed for quantitative assessment of
      injury and applied to the data set. Image-based findings were validated with
      histological visual gradings that describe degree of injury and measurement of
      epithelial thickness. RESULTS: Distinct differences in PI staining were detected
      following BZK and N-9 treatment. Images from controls had uniformly distributed
      nuclei with defined borders, while those after BZK or N-9 showed heavily stained
      and disrupted nuclei, which increased in proportion to injury detected on
      histology. The confocal scoring system revealed statistically significant scores
      for each agent versus PBS controls with the exception of HEC and were consistent
      with histology scores of injury. CONCLUSIONS: Confocal microendoscopy provides a
      sensitive, objective, and quantitative approach for non-invasive assessment of
      vaginal epithelial integrity and could serve as a tool for real-time safety
      evaluation of emerging intravaginal topical agents.

PMID- 22375799
TI  - Narrowing the gaps in research for women in the military and veterans.

PMID- 22375801
TI  - An Internet survey of demographic and health factors associated with risk of
      sexual dysfunction in women who have sex with women.
AB  - INTRODUCTION: There has been scant attention to predictors of sexual dysfunction
      in women who have sex with women (WSW). AIM: To investigate the associations of
      high risk for sexual dysfunction in an Internet cohort of WSW. MAIN OUTCOME
      MEASURE: A modified version of the Female Sexual Function Index (FSFI) was used
      to quantify each subject's sexual function. METHODS: Women who have sex with
      women were invited to participate in an Internet-based survey by invitations
      posted on e-mail listservs and on social media sites catering to WSW.
      Ethnodemographic, health status, and sexual/relationship data were collected.
      RESULTS: The study was completed by 2,433 adult women. Of these, 1,566
      participants had complete data on the FSFI and comprised the study cohort; 388
      (24.8%) met the FSFI criteria for high risk of female sexual dysfunction (HRFSD).
      On multivariable analysis, the following variables were found to be independently
      associated with the HRFSD; moderate or severe subjective bother regarding sexual
      function (OR 4.8, 95% CI 3.0-7.9 and 13.7, 95% CI 7.5-25.1, respectively),
      overactive bladder (OAB) (OR 2.1, 95% CI 1.0-4.5), having a nonfemale or no
      partner (OR 2.3, 95% CI 1.1-4.7 and 3.2, 95% CI 2.0-5.2, respectively). A history
      of pregnancy was associated with lower odds of HRFSD (OR 0.567, 95% CI 0.37
      0.87). Mean FSFI domain scores for all domains except desire were negatively
      impacted by partner factors and OAB. CONCLUSIONS: A single-item question on
      sexual bother is strongly predictive of potentially distressing sexual problems
      in the WSW. A number of health and social factors are associated with risk of
      sexual problems in the WSW. Assessment of sexual well-being in the WSW is a
      priority for practicing healthcare providers.

PMID- 22375802
TI  - Quantitative proteomic analysis of mouse embryonic fibroblasts and induced
      pluripotent stem cells using 16O/18O labeling.
AB  - Induced pluripotent stem cells (iPSC) hold great promise for regenerative
      medicine as well as for investigations into the pathogenesis and treatment of
      various diseases. Understanding of key intracellular signaling pathways and
      protein targets that control development of iPSC from somatic cells is essential
      for designing new approaches to improve reprogramming efficiency. Here, we report
      the development and application of an integrated quantitative proteomics platform
      for investigating differences in protein expressions between mouse embryonic
      fibroblasts (MEF) and MEF-derived iPSC. This platform consists of 16O/18O
      labeling, multidimensional peptide separation coupled with tandem mass
      spectrometry, and data analysis with UNiquant software. With this platform, a
      total of 2481 proteins were identified and quantified from the 16O/18O-labeled
      MEF-iPSC proteome mixtures with a false discovery rate of 0.01. Among them, 218
      proteins were significantly upregulated, while 247 proteins were significantly
      downregulated in iPSC compared to MEF. Many nuclear proteins, including Hdac1,
      Dnmt1, Pcna, Ccnd1, Smarcc1, and subunits in DNA replication and RNA polymerase
      II complex, were found to be enhanced in iPSC. Protein network analysis revealed
      that Pcna functions as a hub orchestrating complicated mechanisms including DNA
      replication, epigenetic inheritance (Dnmt1), and chromatin remodeling (Smarcc1)
      to reprogram MEF and maintain stemness of iPSC.

PMID- 22375800
TI  - Cognitive profiles in heart failure: a cluster analytic approach.
AB  - Cognitive impairment is common among individuals with heart failure (HF), but the
      exact nature of these impairments remains unclear. The current study examined 140
      older adults with heart failure and sought to determine whether there are
      distinct cognitive profiles using a cluster analytic approach. Results indicated
      three unique profiles comprising individuals who were cognitively intact, memory
      impaired, and globally impaired. Clusters differed on several important
      demographic and clinical characteristics. These findings suggest that cognitive
      impairment in persons with HF is more heterogeneous than commonly believed and
      has important implications for treatment recommendations.

PMID- 22375803
TI  - Trauma, attachment, and intimate relationships.
AB  - Intimate relationships can both affect and be affected by trauma and its
      sequelae. This special issue highlights research on trauma, attachment, and
      intimate relationships. Several themes emerged. One theme is the exploration of
      the associations between a history of trauma and relational variables, with an
      emphasis on models using these variables as mediators. Given the significance of
      secure attachment for healthy relationships, it is not surprising that attachment
      emerges as another theme of this issue. Moreover, a key component of
      relationships is trust, and so a further theme of this issue is betrayal trauma
      (J. J.  Freyd, 1996 ). As the work included in this special issue makes clear,
      intimate relationships of all types are important for the psychological health of
      those exposed to traumatic events. In order to best help trauma survivors and
      those close to them, it is imperative that research exploring these issues be
      presented to research communities, clinical practitioners, and the public in
      general. This special issue serves as one step toward that objective.

PMID- 22375804
TI  - Beyond Criterion A1: the effects of relational and non-relational traumatic
      events.
AB  - Trauma research has historically focused on Criterion A1 traumas, neglecting many
      other negative interpersonal events that have been shown to lead to posttraumatic
      stress disorder (PTSD; S. L.  Anders, P. A. Frazier, & S. Frankfurt, 2011 ).
      Trauma research has also focused primarily on PTSD and neglected other important
      outcomes, such as relationship functioning. This study aimed to assess a broader
      range of events, including many Criterion A1 interpersonal events; assess the
      cumulative impact of event exposure; and examine the relation between event
      exposure and a broad range of outcomes, including relationship functioning. A
      sample of 181 undergraduate students completed measures assessing exposure to a
      broad range of events, their worst lifetime event, and current psychological
      (e.g., psychological distress) and relationship (e.g., partner trust)
      functioning. Results suggested that non-Criterion A1 relational events were very
      common in our sample. The number of lifetime relational events experienced,
      whether Criterion A1 or non-Criterion A1, was strongly and consistently
      associated with all outcomes. The number of lifetime Criterion A1 non-relational
      events experienced was significantly associated with current PTSD symptoms but
      was not associated with other mental health and relationship outcomes. No
      differences were found between Criterion A1 relational, non-Criterion A1
      relational, and Criterion A1 non-relational worst events on any of the mental
      health or relationship measures. Implications for further research and
      interventions are discussed.

PMID- 22375805
TI  - Partner preferences among survivors of betrayal trauma.
AB  - Betrayal trauma theory suggests that social and cognitive development may be
      affected by early trauma such that individuals develop survival strategies,
      particularly dissociation and lack of betrayal awareness, that may place them at
      risk for further victimization. Several experiences of victimization in the
      context of relationships predicated on trust and dependence may contribute to the
      development of relational schema whereby abuse is perceived as normal. The
      current exploratory study investigates interpersonal trauma as an early
      experience that might impact the traits that are desired in potential romantic
      partners. Participants in the current study were asked to rate the desirability
      of several characteristics in potential romantic partners. Although loyalty was
      desirable to most participants regardless of their trauma history, those who
      reported experiences of high betrayal trauma rated loyalty less desirable than
      those who reported experiences of traumas that were low and medium in betrayal.
      Participants who reported experiences of revictimization (defined as the
      experience of trauma perpetrated by a close other during 2 different
      developmental periods) differed from participants who only reported 1 experience
      of high betrayal trauma in their self-reported desire for a romantic partner who
      possessed the traits of sincerity and trustworthiness. Preference for a partner
      who uses the tactic of verbal aggression was also associated with revictimization
      status. These preliminary findings suggest that victimization perpetrated by
      close others may affect partner preferences.

PMID- 22375806
TI  - I get no respect: the relationship between betrayal trauma and romantic
      relationship functioning.
AB  - The current study explored the association among young adults' (N = 86)
      experiences of betrayal traumas (interpersonal trauma perpetrated by someone
      close) prior to age 18, psychological well-being, attachment styles, and romantic
      relationship function (i.e., dedication, relationship adjustment, and perceived
      partner respect). Based on betrayal trauma theory, we posited that participants'
      reports of betrayal traumas would be negatively related to their perceptions of
      respect from their partner but would not relate to their perceptions of
      relationship adjustment or dedication. Furthermore, we expected that the
      relationship between betrayal traumas and respect would be mediated by
      participants' attachment style and psychological well-being. Results identified a
      negative association between betrayal traumas and psychological well-being and a
      positive association between betrayal trauma and anxious and avoidant attachment.
      Betrayal traumas were also shown to be negatively related to partner respect and
      not significantly associated with dedication and relationship adjustment. Anxious
      attachment and psychological well-being were significant mediators for the
      relationship between betrayal traumas and perceived respect.

PMID- 22375807
TI  - Attachment and health care relationships in low-income women with trauma
      histories: a qualitative study.
AB  - Few studies have examined the relationship between low-income, traumatized women
      and their health care providers. In this study we interviewed 23 women from
      primary care and social service settings for the underserved about trauma,
      attachment, psychiatric symptoms, and reports of their interactions with primary
      care providers. Nearly all reported trauma exposure, and 17% had current
      posttraumatic stress disorder. About half were categorized as Unresolved with
      regard to attachment state of mind. Analyses of a health experiences interview
      showed that women with Unresolved attachment reported significantly more negative
      interactions with providers. Attachment may play a role in the relationship
      between trauma and health care interactions with providers, indicating the need
      for further study of this relationship and suggesting intervention strategies to
      help both parties contribute to a more collaborative process.

PMID- 22375808
TI  - Attachment and coping as facilitators of posttraumatic growth in Turkish
      university students experiencing traumatic events.
AB  - This study was designed to explore the role of attachment and coping as
      facilitators of posttraumatic growth (PTG) in a sample of Turkish university
      students who experienced traumatic life events. Participants who reported a
      traumatic event from a list were asked to choose the most distressing one; to
      answer questions related to the impact of the trauma; and to fill out measures of
      attachment styles, ways of coping, and PTG. PTG was regressed on gender, trauma
      related factors, attachment styles, and coping styles in order to examine the
      associations with PTG. Felt helplessness and horror, fatalistic coping, and
      optimistic coping were significant predictors of PTG. Fatalistic coping partially
      mediated the relationship between attachment anxiety and PTG.

PMID- 22375809
TI  - The ties that bind: understanding the impact of sexual assault disclosure on
      survivors' relationships with friends, family, and partners.
AB  - A growing body of research suggests that the type of social reactions sexual
      assault survivors receive from others can have a profound impact on their health
      and well-being. Far less is known about the impact of social reactions on the
      ensuing relationship between survivors and the people to whom they disclose. The
      current study sought to address this gap in the literature by examining the
      impact of disclosure on survivors' relationships with friends, family members,
      and romantic partners. A total of 76 rape survivors described 153 different
      disclosures to informal support providers. Qualitative analysis suggested that
      most relationships either were strengthened or remained strong following the
      disclosure, but a substantial number of survivors described relationships that
      deteriorated or remained poor following the disclosure. These outcomes were
      related to the quality of the relationship prior to the disclosure and to
      survivors' perceptions of the reactions they received during the disclosure.
      Implications of these findings for research and practice are discussed.

PMID- 22375810
TI  - Relational health as a mediator between betrayal trauma and borderline
      personality disorder.
AB  - A frequently studied hypothesized cause of borderline personality disorder (BPD)
      is experiencing interpersonal trauma. A recent study by L. A.  Kaehler and J. J.
      Freyd (2009 ) found a connection between betrayal trauma and BPD characteristics,
      with higher betrayal traumas associated with greater BPD characteristics. The
      present study seeks to expand upon that study by investigating relational health
      as a potential mediator for the association between betrayal trauma and BPD. A
      sample of 165 college students completed measures of betrayal trauma life events,
      relational health, and BPD traits. Mediation analyses showed significant partial
      mediation for total relational health (bootstrap coefficient = .0168) and its
      community subscale (bootstrap coefficient = .0204); however, significant
      mediating effects for the mentor and friend subscales were not found. Given the
      significant finding for only the community subscale, which may be driving the
      total relational health effect seen, the results suggest that connection with a
      valued community may be an important protective factor for BPD after one
      experiences betrayal trauma.

PMID- 22375812
TI  - Quaternary ammonium bromide surfactant adsorption on low-index surfaces of gold.
      1. Au(111).
AB  - The coadsorption of the anionic and cationic components of a model quaternary
      ammonium bromide surfactant on Au(111) has been measured using the thermodynamics
      of an ideally polarized electrode. The results indicate that both bromide and
      trimethyloctylammonium (OTA(+)) ions are coadsorbed over a broad range of the
      electrical state of the gold surface. At negative polarizations, the Gibbs
      surface excess of the cationic surfactant is largely unperturbed by the presence
      of bromide ions in solution. However, when the Au(111) surface is weakly charged
      the existence of a low-coverage, gaslike phase of adsorbed halide induces an
      appreciable (~25%) enhancement of the interfacial concentration of the cationic
      surfactant ion. At more positive polarizations, the coadsorbed OTA(+)/Br(-) layer
      undergoes at least one phase transition which appears to be concomitant with the
      lifting of the Au(111) reconstruction and the formation of a densely packed
      bromide adlayer. In the absence of coadsorbed halide, the OTA(+) ions are
      completely desorbed from the Au(111) surface at the most positive electrode
      polarizations studied. However, with NaBr present in the electrolyte, a high
      surface excess of bromide species leads to the stabilization of adsorbed OTA(+)
      at such positive potentials (or equivalent charge densities).

PMID- 22375811
TI  - Evidence of diversity and recombination in Arsenophonus symbionts of the Bemisia
      tabaci species complex.
AB  - BACKGROUND: Maternally inherited bacterial symbionts infecting arthropods have
      major implications on host ecology and evolution. Among them, the genus
      Arsenophonus is particularly characterized by a large host spectrum and a wide
      range of symbiotic relationships (from mutualism to parasitism), making it a good
      model to study the evolution of host-symbiont associations. However, few data are
      available on the diversity and distribution of Arsenophonus within host lineages.
      Here, we propose a survey on Arsenophonus diversity in whitefly species
      (Hemiptera), in particular the Bemisia tabaci species complex. This polyphagous
      insect pest is composed of genetic groups that differ in many ecological aspects.
      They harbor specific bacterial communities, among them several lineages of
      Arsenophonus, enabling a study of the evolutionary history of these bacteria at a
      fine host taxonomic level, in association to host geographical range and ecology.
      RESULTS: Among 152 individuals, our analysis identified 19 allelic profiles and 6
      phylogenetic groups, demonstrating this bacterium's high diversity. These groups,
      based on Arsenophonus phylogeny, correlated with B. tabaci genetic groups with
      two exceptions reflecting horizontal transfers. None of three genes analyzed
      provided evidence of intragenic recombination, but intergenic recombination
      events were detected. A mutation inducing a STOP codon on one gene in a strain
      infecting one B. tabaci genetic group was also found. Phylogenetic analyses of
      the three concatenated loci revealed the existence of two clades of Arsenophonus.
      One, composed of strains found in other Hemiptera, could be the ancestral clade
      in whiteflies. The other, which regroups strains found in Hymenoptera and
      Diptera, may have been acquired more recently by whiteflies through lateral
      transfers. CONCLUSIONS: This analysis of the genus Arsenophonus revealed a
      diversity within the B. tabaci species complex which resembles that reported on
      the larger scale of insect taxonomy. We also provide evidence for recombination
      events within the Arsenophonus genome and horizontal transmission of strains
      among insect taxa. This work provides further insight into the evolution of the
      Arsenophonus genome, the infection dynamics of this bacterium and its influence
      on its insect host's ecology.

PMID- 22375813
TI  - Male migration and risky sexual behavior in rural India: is the place of origin
      critical for HIV prevention programs?
AB  - BACKGROUND: Recent studies of male migrants in India indicate that those who are
      infected with HIV are spreading the epidemic from high risk populations in high
      prevalence areas to populations in low prevalence areas. In this context, migrant
      men are believed to initiate and have risky sexual behaviors in places of
      destination and not in places of origin. The paucity of information on men's
      risky sexual behaviors in places of origin limits the decision to initiate HIV
      prevention interventions among populations in high out-migration areas in India.
      METHODS: A cross-sectional behavioral survey was conducted among non-migrants,
      returned migrants (with a history of migration), and active (current) migrants in
      rural areas across two districts with high levels of male out-migration: Prakasam
      district in Andhra Pradesh and Azamgarh district in Uttar Pradesh. Surveys
      assessed participant demographics, migration status, migration history, and
      sexual behavior along the migration routes, place of initiation of sex. District
      stratified regression models were used to understand the associations between
      migration and risky sexual behaviors (number of partners, condom use at last sex)
      and descriptive analyses of migrants' place of sexual initiation and continuation
      along migration routes. RESULTS: The average age at migration of our study sample
      was 19 years. Adjusted regression analyses revealed that active migrants were
      more likely to engage in sex with sex workers in the past 12 months (Prakasam: 15
      percent vs. 8 percent; adjusted odds ratio (aOR)=2.1, 95% CI 1.2-3.4; Azamgarh:
      19 percent vs.7 percent; aOR=4.0, 95% CI 2.4-6.6) as well as have multiple (3+)
      sex partners (Prakasam: 18 percent vs. 9 percent; aOR=2.0, 95% CI 1.3-3.2;
      Azamgarh: 28 percent vs. 21 percent; aOR=1.9, 95% CI 1.2-3.0) than non-migrants.
      Contrary to popular belief, a high proportion of active and returned migrants
      (almost 75 percent of those who had sex) initiated sex at the place of origin
      before migrating, which is equivalent to the proportion of non-migrants who
      engaged in sex with sex workers as well as with casual unpaid partners. Moreover,
      non-migrants were more likely than migrants to engage in unprotected sex.
      CONCLUSION: Findings of this study document that returned migrants and active
      migrants have higher sexual risk behaviors than the non-migrants. Most migrants
      initiate non-marital sex in the place of origin and many continue these behaviors
      in places of destination. Migrants' destination area behaviors are linked to sex
      with sex workers and they continue to practice such behaviors in the place of
      origin as well. Unprotected sex in places of destination with high HIV prevalence
      settings poses a risk of transmission from high risk population groups to
      migrants, and in turn to their married and other sexual partners in places of
      origin. These findings suggest the need for controlling the spread of HIV among
      both men and women resulting from unsafe sex in places of origin that have high
      vulnerability due to the frequent migratory nature of populations.

PMID- 22375815
TI  - Intrauterine bone fragments and endometrial plaque of osseous metaplasia.

PMID- 22375814
TI  - A chemical screen identifies class a g-protein coupled receptors as regulators of
      cilia.
AB  - Normal cilia length and motility are critical for proper cellular function. Prior
      studies of the regulation of ciliary structure and length have primarily focused
      on the intraflagellar transport machinery and motor proteins required for ciliary
      assembly and disassembly. However, several mutants with abnormal length flagella
      highlight the importance of signaling proteins as well. In this study, an
      unbiased chemical screen was performed to uncover signaling pathways that are
      critical for ciliogenesis and length regulation using flagella of the green alga
      Chlamydomonas reinhardtii as a model. The annotated Sigma LOPAC1280 chemical
      library was screened for effects on flagellar length, motility, and severing as
      well as cell viability. Assay data were clustered to identify pathways regulating
      flagella. The most frequent target found to be involved in flagellar length
      regulation was the family of dopamine binding G-protein coupled receptors
      (GPCRs). In mammalian cells, cilium length could indeed be altered with
      expression of the dopamine D1 receptor. Our screen thus reveals signaling
      pathways that are potentially critical for ciliary formation, resorption, and
      length maintenance, which represent candidate targets for therapeutic
      intervention of disorders involving ciliary malformation and malfunction.

PMID- 22375816
TI  - Imaging in vivo redox status in high spatial resolution with OMRI.
AB  - Redox-reactions are playing a significant role in regulation of homeostasis of
      organism. Disorder of the redox-status is related with the onset and/or
      propagation of oxidative diseases such as lifestyle-related diseases, including
      cancers and cardiac diseases, etc. In vivo imaging of redox-status is thereby
      important in the analysis of mechanisms of oxidative diseases and developments of
      new medicines for the diseases. Aminoxyl radicals are redox-sensitive reporter
      molecules, which lose their paramagnetic moiety by reactions of free radicals or
      reducing compounds. Electron spin resonance (ESR) technique has been used to
      measure the molecules in vivo. In vivo spatial resolution in ESR imaging is in
      the range of a few millimeters and is not sufficient for the detailed diagnosis
      of disease models. Overhauser enhanced MRI (OMRI) is an emerging free radical
      imaging technique, which utilised electron-proton coupling to image the
      distribution of free radicals. In vivo imaging of redox-status is applicable with
      OMRI/aminoxyl radical technique. The detailed imaging analysis was demonstrated
      in oxidative diseases, such as tumour-bearing, neurodegeneration or gastric ulcer
      models. The OMRI/aminoxyl radical technique has a large potential as a diagnostic
      system for biomedical applications in the future.

PMID- 22375817
TI  - A new species of Ascocotyle (Trematoda: Heterophyidae) from the South American
      sea lion, Otaria flavescens, off Patagonia, Argentina.
AB  - We describe a new heterophyid species, Ascocotyle (Ascocotyle) patagoniensis n.
      sp., based on specimens collected from the intestines of the South American sea
      lion Otaria flavescens from Patagonia (Argentina). Ascocotyle (A.) patagoniensis
      n. sp. is distinguished from the other species of the subgenus by the number of
      circumoral spines, which are arranged in 2 rows of 18 to 23. The new species also
      differs from the other species in having a gonotyl without papillae. The
      specimens exhibited the widest seminal receptacle described for a species of this
      subgenus. Species of the subgenus Ascocotyle usually infect fish-eating birds or
      mammals in freshwater or brackish habitats. Ascocotyle (A.) patagoniensis n. sp.
      is the first species of the subgenus described from a marine mammal. However, no
      metacercariae of Ascocotyle spp. were found in 542 marine teleosts from 20
      species collected in the same locality. The life cycle of the marine species from
      the Ascocotyle -complex infecting pinnipeds remains elusive.

PMID- 22375818
TI  - Sensing with multipolar second harmonic generation from spherical metallic
      nanoparticles.
AB  - We show that sensing in the nonlinear optical regime using multipolar surface
      plasmon resonances is more sensitive in comparison to sensing in the linear
      optical regime. Mie theory, and its extension to the second harmonic generation
      from a metallic nanosphere, is used to describe multipolar second harmonic
      generation from silver metallic nanoparticles. The standard figure of merit of a
      potential plasmonic sensor based on this principle is then calculated. We finally
      demonstrate that such a sensor is more sensitive to optical refraction index
      changes occurring in the vicinity of the metallic nanoparticle than its linear
      counterpart.

PMID- 22375820
TI  - Preparation of samarium(II) iodide: quantitative evaluation of the effect of
      water, oxygen, and peroxide content, preparative methods, and the activation of
      samarium metal.
AB  - Samarium(II) iodide (SmI(2)) is one of the most important reducing agents in
      organic synthesis. Synthetic chemistry promoted by SmI(2) depends on the
      efficient and reliable preparation of the reagent. Unfortunately, users can
      experience difficulties preparing the reagent, and this has prevented realization
      of the full synthetic potential of SmI(2). To provide synthetic chemists with
      general and reliable methods for the preparation of SmI(2), a systematic
      evaluation of the factors involved in its synthesis has been carried out. Our
      studies confirm that SmI(2) is a user-friendly reagent. Factors such as water,
      oxygen, and peroxide content in THF have little influence on the synthesis of
      SmI(2). In addition, the use of specialized glovebox equipment or Schlenk
      techniques is not required for the preparation of SmI(2). However, our studies
      suggest that the quality of samarium metal is an important factor and that the
      use of low quality metal is the main cause of failed preparations of the reagent.
      Accordingly, we report a straightforward method for activation of "inactive"
      samarium metal and demonstrate the broad utility of this protocol through the
      electron transfer reductions of a range of substrates using SmI(2) prepared from
      otherwise "inactive" metal. An investigation into the stability of SmI(2)
      solutions and an evaluation of commercially available solutions of the reagent is
      also reported.

PMID- 22375821
TI  - Chiral conducting salts of nickel dithiolene complexes.
AB  - Conducting and chiral [Ni(dmit)(2)] dithiolene salts were obtained by
      electrocrystallization of the radical [n-Bu(4)N][Ni(dmit)(2)] salt in the
      presence of chiral, enantiopure trimethylammonium cations. Three different
      cations were investigated, namely, (R)-Ph(Me)HC*-NMe(3)(+), (S)-((t)Bu)(Me)HC*
      NMe(3)(+), and (S)-(1-Napht)MeHC*-NMe(3)(+), noted (R)-1, (S)-2, and (S)-3. Salts
      of 1:3 stoichiometry were obtained with (R)-1 and (S)-2, formulated as [(R)
      1][Ni(dmit)(2)](3) and [(S)-2][Ni(dmit)(2)](3).(CH(3)CN)(2). They both
      crystallize  in the P2(1)2(1)2(1) chiral space group, with three
      crystallographically independent complexes exhibiting different oxidation
      degrees. Another salt with 2:5 stoichiometry was isolated with (S)-3. The
      semiconducting character of the three salts (sigma(RT) = 20-30 * 10(-3) S cm(-1))
      finds its origin in a strong electron localization, favored by the large number
      of crystallographically independent [Ni(dmit)(2)] complexes in these chiral
      structures and their association into weakly interacting dimeric or trimeric
      motifs. Racemic salts with the same cations, obtained only with difficulties with
      the tert-butyl-containing (rac)-2 cation, afforded similar trimerized structures.
      The observed unusual stoichiometry and strong charge localization is tentatively
      assigned to the size and anisotropic charge distribution of the cations.

PMID- 22375822
TI  - Influence of thermal treatment on color, enzyme activities, and antioxidant
      capacity of innovative pastelike parsley products.
AB  - Conventional spice powders are often characterized by low sensory quality and
      high microbial loads. Furthermore, genuine enzymes are only inhibited but not
      entirely inactivated upon drying, so that they may regain their activity upon
      rehydration of dried foods. To overcome these problems, initial heating was
      applied in the present study as the first process step for the production of
      innovative pastelike parsley products. For this purpose, fresh parsley was
      blanched (80, 90, and 100  degrees C for 1-10 min) and subsequently comminuted to
      form a paste. Alternatively, mincing was carried out prior to heat treatment.
      Regardless of temperature, the color of the latter product did not show any
      change after heating for 1 min. With progressing exposure time the green color
      turned to olive hues due to marked pheophytin formation. Inactivation of genuine
      peroxidase (POD) and polyphenol oxidase (PPO) was achieved at all temperature
      time regimes applied. In contrast, the parsley products obtained after immediate
      water-blanching were characterized by brighter green colors and enhanced pigment
      retention. With the exception of the variants water-blanched at 80  degrees C,
      POD and PPO were completely inactivated at any of the thermal treatments.
      Furthermore, in water-blanched samples, antioxidant capacities as determined by
      the TEAC and FRAP assays were even enhanced compared to unheated parsley, whereas
      a decrease of phenolic contents could not be prevented. Consequently, the
      innovative process presented in this study allows the production of novel herb
      and spice products characterized by improved sensory quality as compared to
      conventional spice products.

PMID- 22375824
TI  - Identification and analysis of flagellar coexpressed determinants (Feds) of
      Campylobacter jejuni involved in colonization.
AB  - The flagellum of Campylobacter jejuni provides motility essential for commensal
      colonization of the intestinal tract of avian species and infection of humans
      resulting in diarrhoeal disease. Additionally, the flagellar type III secretion
      system has been reported to secrete proteins such as CiaI that influence invasion
      of human intestinal cells and possibly pathogenesis. The flagellar regulatory
      system ultimately influences sigma(28)  activity required for expression of the
      FlaA major flagellin and other flagellar filament proteins. In this work, we
      discovered that transcription of ciaI and four genes we propose annotating as
      feds (for flagellar coexpressed determinants) is dependent upon sigma(28) , but
      these genes are not required for motility. Instead, the Feds and CiaI are
      involved in commensal colonization of chicks, with FedA additionally involved in
      promoting invasion of human intestinal cells. We also discovered that the major
      flagellin influences production, stability or secretion of sigma(28) -dependent
      proteins. Specific transcriptional and translational mechanisms affecting CiaI
      were identified and domains of CiaI were analysed for importance in commensalism
      or invasion. Our work broadens the genes controlled by the flagellar regulatory
      system and implicates this system in co-ordinating production of colonization and
      virulence determinants with flagella, which together are required for optimal
      interactions with diverse hosts.

PMID- 22375826
TI  - Correlates of depression among caregivers of children affected by HIV/AIDS in
      Uganda: findings from the Suubi-Maka family study.
AB  - This study uses the baseline (wave 1) data from a four-year (2008-2012)
      longitudinal study called the Suubi-Maka family economic empowerment intervention
      for AIDS-orphaned children in Uganda funded by the National Institute of Mental
      Health (Grant # RMH081763A). Specifically, using baseline data from the Suubi
      Maka study, this article provides a contextualized understanding of depression
      levels among caregivers for AIDS-orphaned children in two rural communities
      heavily affected by AIDS in Uganda: Rakai and Masaka districts. Using baseline
      data collected from caregivers of children orphaned by AIDS (N=297) the study
      examines the factors that influence reported depression levels of caregivers of
      AIDS-orphaned children in rural communities of Uganda. We specifically use
      ordinary least squares regression methods. In the analysis we control for several
      demographic factors, including age, gender, assets, social support, and
      caregiving status. We find that caregivers' reported economic status and social
      support system are highly correlated with caregivers' reported depression scores.
      Specifically, caregivers with cash savings and a strong family support system
      reported better depression scores. These findings have implications for community
      development practice and programming. Specifically, the study highlights a need
      for family economic empowerment programs and, strengthened family support among
      caregivers for AIDS-orphaned children, especially those caregivers with reported
      poor mental health functioning.

PMID- 22375827
TI  - Gender differences in patients' perceptions of inpatient care.
AB  - OBJECTIVE: To examine gender differences in inpatient experiences and how they
      vary by dimensions of care and other patient characteristics. DATA SOURCE: A
      total of 1,971,632 patients (medical and surgical service lines) discharged from
      3,830 hospitals, July 2007-June 2008, and completing the HCAHPS survey. STUDY
      DESIGN: We compare the experiences of male and female inpatients on 10 HCAHPS
      dimensions using multiple linear regression, adjusting for survey mode and
      patient mix. Additional models add additional patient characteristics and their
      interactions with patient gender. PRINCIPAL FINDINGS: We find generally less
      positive experiences for women than men, especially for Communication about
      Medicines, Discharge Information, and Cleanliness. Gender differences are similar
      in magnitude to previously reported HCAHPS differences by race/ethnicity. The
      gender gap is generally larger for older patients and for patients with worse
      self-reported health status. Gender disparities are largest in for-profit
      hospitals. CONCLUSIONS: Targeting the experiences of women may be a promising
      means of improving overall patient experience scores (because women comprise a
      majority of all inpatients); the experiences of older and sicker women, and those
      in for-profit hospitals, may merit additional examination.

PMID- 22375828
TI  - Male responsibility and maternal morbidity: a cross-sectional study in two
      Nigerian states.
AB  - BACKGROUND: Nigeria continues to have high rates of maternal morbidity and
      mortality. This is partly associated with lack of adequate obstetric care, partly
      with high risks in pregnancy, including heavy work. We examined actionable risk
      factors and underlying determinants at community level in Bauchi and Cross River
      States of Nigeria, including several related to male responsibility in pregnancy.
      METHOD: In 2009, field teams visited a stratified (urban/rural) last stage random
      sample of 180 enumeration areas drawn from the most recent censuses in each of
      Bauchi and Cross River states. A structured questionnaire administered in face-to
      face interviews with women aged 15-49 years documented education, income, recent
      birth history, knowledge and attitudes related to safe birth, and deliveries in
      the last three years. Closed questions covered female genital mutilation,
      intimate partner violence (IPV) in the last year, IPV during the last pregnancy,
      work during the last pregnancy, and support during pregnancy. The outcome was
      complications in pregnancy and delivery (eclampsia, sepsis, bleeding) among
      survivors of childbirth in the last three years. We adjusted bivariate and
      multivariate analysis for clustering. FINDINGS: The most consistent and prominent
      of 28 candidate risk factors and underlying determinants for non-fatal maternal
      morbidity was intimate partner violence (IPV) during pregnancy (ORa 2.15, 95%CIca
      1.43-3.24 in Bauchi and ORa 1.5, 95%CI 1.20-2.03 in Cross River). Other spouse
      related factors in the multivariate model included not discussing pregnancy with
      the spouse and, independently, IPV in the last year. Shortage of food in the last
      week was a factor in both Bauchi (ORa 1.66, 95%CIca 1.22-2.26) and Cross River
      (ORa 1.32, 95%CIca 1.15-1.53). Female genital mutilation was a factor among less
      well to do Bauchi women (ORa 2.1, 95%CIca 1.39-3.17) and all Cross River women
      (ORa 1.23, 95%CIca 1.1-1.5). INTERPRETATION: Enhancing clinical protocols and
      skills can only benefit women in Nigeria and elsewhere. But the violence women
      experience throughout their lives--genital mutilation, domestic violence, and
      steep power gradients--is accentuated through pregnancy and childbirth, when
      women are most vulnerable. IPV especially in pregnancy, women's fear of husbands
      or partners and not discussing pregnancy are all within men's capacity to change.

PMID- 22375829
TI  - The effect of prolapse repair on sexual function in women.
AB  - INTRODUCTION: Sexual dysfunction is common in women with pelvic organ prolapse
      (POP). Treatment of symptomatic prolapse often requires surgery. The outcome of
      prolapse symptoms following surgery is well studied and reported, but evidence on
      outcomes of sexual function following pelvic reconstructive surgeries is limited.
      AIM: The objective of this study was to assess the impact of different forms of
      surgery for POP on sexual function using prospectively collected data. METHODS:
      In this ethically approved project, data were collected prospectively for women
      undergoing prolapse repair between 2008 and 2010 and were stratified into four
      groups: "posterior repair,""anterior repair,""anterior repair with vaginal
      hysterectomy," and "combined anterior and posterior repair." The electronic
      personal assessment questionnaire-pelvic floor (ePAQ-PF) was used to assess
      symptoms. The sexual dimension of ePAQ-PF computes domain scores for sexual
      dysfunction secondary to vaginal symptoms and dyspareunia on a scale of 0-100 (0
      = best possible and 100 = worst possible health status). ePAQ-PF was completed in
      123 sexually active women both pre- and 3-6 month postoperatively. Results were
      analyzed using SPSS (SPSS Inc., Chicago, IL, USA). Pre- and postoperative scores
      for each domain were compared in all groups (Student's t-test). Individual
      symptoms in these domains were compared using Wilcoxon signed-rank test. MAIN
      OUTCOME MEASURES: Change in sexual symptoms and dyspareunia following prolapse
      surgery in each group. RESULTS: Women undergoing anterior repair or anterior
      repair and vaginal hysterectomy reported significant improvement in sexual
      symptoms and dyspareunia. Women undergoing a posterior repair in isolation had
      improved sexual function following surgery though improvement in dyspareunia was
      not significant. Women undergoing combined anterior and posterior repair had the
      least improvement in sexual function. CONCLUSIONS: Sexual function improves in
      women following pelvic reconstructive surgery, but the improvement is more
      substantial following anterior repair either alone or in combination with a
      vaginal hysterectomy when compared with posterior repair.

PMID- 22375830
TI  - Pediatric multiple sclerosis: what we know and where are we headed?
AB  - Multiple Sclerosis (MS), an autoimmune mediated disease of the central nervous
      system, has historically been considered a disease of young adulthood. However,
      there has been increasing recognition that the disease can occur in adolescence
      and even early childhood and recent years have witnessed a surge of studies
      documenting the clinical features of the disease as it pertains to this young
      population. The purpose of this article is to review the literature on MS in
      childhood and adolescence, including the clinical presentation of the disease in
      this group, neuropathology and pathogenesis, magnetic resonance imaging findings,
      as well as neuropsychological and psychosocial considerations.

PMID- 22375831
TI  - Identification of core components and transient interactors of the peroxisomal
      importomer by dual-track stable isotope labeling with amino acids in cell culture
      analysis.
AB  - The importomer complex plays an essential role in the biogenesis of peroxisomes
      by mediating the translocation of matrix proteins across the organellar membrane.
      A central part of this highly dynamic import machinery is the docking complex
      consisting of Pex14p, Pex13p, and Pex17p that is linked to the RING finger
      complex (Pex2p, Pex10p, Pex12p) via Pex8p. To gain detailed knowledge on the
      molecular players governing peroxisomal matrix protein import and, thus, the
      integrity and functionality of peroxisomes, we aimed at a most comprehensive
      investigation of stable and transient interaction partners of Pex14p, the central
      component of the importomer. To this end, we performed a thorough quantitative
      proteomics study based on epitope tagging of Pex14p combined with dual-track
      stable isotope labeling with amino acids in cell culture-mass spectrometry (SILAC
      MS) analysis of affinity-purified Pex14p complexes and statistics. The results
      led to the establishment of the so far most extensive Pex14p interactome,
      comprising 9 core and further 12 transient components. We confirmed virtually all
      known Pex14p interaction partners including the core constituents of the
      importomer as well as Pex5p, Pex11p, Pex15p, and Dyn2p. More importantly, we
      identified new transient interaction partners (Pex25p, Hrr25p, Esl2p, prohibitin)
      that provide a valuable resource for future investigations on the functionality,
      dynamics, and regulation of the peroxisomal importomer.

PMID- 22375832
TI  - Evaluation of microscopic observation drug susceptibility assay for diagnosis of
      multidrug-resistant tuberculosis in Viet Nam.
AB  - BACKGROUND: Early diagnosis of tuberculosis (TB) and multidrug resistant
      tuberculosis (MDR TB) is important for the elimination of TB. We evaluated the
      microscopic observation drug susceptibility (MODS) assay as a direct rapid drug
      susceptibility testing (DST) method for MDR-TB screening in sputum samples
      METHODS: All adult TB suspects, who were newly presenting to Pham Ngoc Thach
      Hospital from August to November 2008 were enrolled into the study. Processed
      sputum samples were used for DST by MODS (DST-MODS) (Rifampicin (RIF) 1 MUg/ml
      and Isoniazid (INH) 0.4 MUg/ml), MGIT culture (Mycobacterial Growth Indicator
      Tube) and Lowenstein Jensen (LJ) culture. Cultures positive by either MGIT or LJ
      were used for proportional DST (DST-LJ) (RIF 40 MUg/ml and INH 0.2 MUg/ml). DST
      profiles on MODS and LJ were compared. Discrepant results were resolved by
      multiplex allele specific PCR (MAS-PCR). RESULTS: Seven hundred and nine TB
      suspects/samples were enrolled into the study, of which 300 samples with DST
      profiles available from both MODS and DST-LJ were analyzed. Cording in MODS was
      unable to correctly identify 3 Mycobacteria Other Than Tuberculosis (MOTT)
      isolates, resulting in 3 false positive TB diagnoses. None of these isolates were
      identified as MDR-TB by MODS. The sensitivity and specificity of MODS were 72.6%
      (95%CI: 59.8, 83.1) and 97.9% (95%CI: 95.2, 99.3), respectively for detection of
      INH resistant isolates, 72.7% (95%CI: 30.9, 93.7) and 99.7% (95%CI: 98.1, 99.9),
      respectively for detecting RIF resistant isolates and 77.8% (95%CI: 39.9, 97.1)
      and 99.7% (95%CI: 98.1, 99.9), respectively for detecting MDR isolates. The
      positive and negative predictive values (PPV and NPV) of DST-MODS were 87.5%
      (95%CI: 47.3, 99.6) and 99.3% (95%CI: 97.5, 99.9) for detection of MDR isolates;
      and the agreement between MODS and DST-LJ was 99.0% (kappa: 0.8, P < 0.001) for
      MDR diagnosis. The low sensitivity of MODS for drug resistance detection was
      probably due to low bacterial load samples and the high INH concentration (0.4
      MUg/ml). The low PPV of DST-MODS may be due to the low MDR-TB rate in the study
      population (3.8%). The turnaround time of DST-MODS was 9 days and 53 days for DST
      LJ. CONCLUSION: The DST-MODS technique is rapid with low contamination rates.
      However, the sensitivity of DST-MODS for detection of INH and RIF resistance in
      this study was lower than reported from other settings.

PMID- 22375834
TI  - Quaternary ammonium bromide surfactant adsorption on low-index surfaces of gold.
      2. Au(100) and the role of crystallographic-dependent adsorption in the formation
      of anisotropic nanoparticles.
AB  - A qualitative and quantitative description of the coadsorption of a quaternary
      ammonium bromide surfactant on Au(100) has been determined using electrochemical
      techniques. Cyclic voltammetry reveals that both the cationic surfactant ion and
      its halide counterion are adsorbed on the surface of unreconstructed Au(100) over
      a wide range of electrode potentials or charge densities. The relative Gibbs
      excesses of the cationic and anionic components of octyltrimethylammonium
      (OTA(+)) bromide have been determined using the thermodynamics of ideally
      polarized electrodes. Coadsorbed OTA(+) does not strongly affect the behavior of
      bromide layers on Au(100) with low-coverage films being replaced by commensurate
      overlayers at positive electrode charge densities. The presence of surface
      bromide allows for the stabilization of adsorbed OTA(+) at positive
      polarizations. Furthermore, charge-induced phase changes in the bromide layer
      lead to subtle but appreciable changes in the surface excesses of OTA(+) ions
      which is consistent with a hierarchical model of surfactant adsorbed upon a
      halide-modified Au(100) surface. A comparison of the OTA(+) adsorption isotherms
      on Au(100) and Au(111) reveals that the presence of coadsorbed bromide does not
      lead to preferential accumulation of cationic surfactant ions on a particular
      crystal facet. These results are inconsistent with explanations of anisotropic
      nanoparticle formation that invoke a thermodynamic argument of preferred
      surfactant adsorption on different crystal facets of an embryonic nanoparticle
      seed crystal.

PMID- 22375833
TI  - Wolbachia surface protein induces innate immune responses in mosquito cells.
AB  - BACKGROUND: Wolbachia endosymbiotic bacteria are capable of inducing chronic
      upregulation of insect immune genes in some situations and this phenotype may
      influence the transmission of important insect-borne pathogens. However the
      molecules involved in these interactions have not been characterized. RESULTS:
      Here we show that recombinant Wolbachia Surface Protein (WSP) stimulates
      increased transcription of immune genes in mosquito cells derived from the
      mosquito Anopheles gambiae, which is naturally uninfected with Wolbachia; at
      least two of the upregulated genes, TEP1 and APL1, are known to be important in
      Plasmodium killing in this species. When cells from Aedes albopictus, which is
      naturally Wolbachia-infected, were challenged with WSP lower levels of
      upregulation were observed than for the An. gambiae cells. CONCLUSIONS: We have
      found that WSP is a strong immune elicitor in a naturally Wolbachia-uninfected
      mosquito species (Anopheles gambiae) while a milder elicitor in a naturally
      infected species (Aedes albopictus). Since the WSP of a mosquito non-native
      (nematode) Wolbachia strain was used, these data suggest that there is a
      generalized tolerance to WSP in Ae. albopictus.

PMID- 22375835
TI  - Molecular and culture-dependent analyses revealed similarities in the endophytic
      bacterial community composition of leaves from three rice (Oryza sativa)
      varieties.
AB  - The endophytic bacterial communities of the three most important rice varieties
      cultivated in Uruguay were compared by a multiphasic approach. Leaves of mature
      plants grown in field experiments for two consecutive crop seasons were studied.
      No significant differences were found in the heterotrophic bacterial density for
      the three varieties. Pantoea ananatis and Pseudomonas syringae constituted 51% of
      the total of the isolates. These species were always present regardless of the
      variety or the season. Molecular analysis based on the 16S rRNA gene was
      performed by terminal restriction fragment length polymorphism (T-RFLP) and
      cloning. T-RFLP analysis revealed that bacterial communities grouped according to
      the variety, although the three varieties presented communities that showed 74%
      or higher similarities. Brevundimonas, the dominant genus in the clone library
      (18% of the clones), which might be present in all varieties according to T-RFLP
      profiles, was not recovered by cultivation. Conversely, bacteria from the genus
      Pseudomonas were not detected in the clone library. These results indicate that
      communities established in leaves of physiologically different rice varieties
      were highly similar and composed by a reduced group of strongly associated and
      persistent bacteria that were partially recovered by cultivation.

PMID- 22375837
TI  - The costs of HIV prevention for different target populations in Mumbai, Thane and
      Bangalore.
AB  - BACKGROUND: Avahan, the India AIDS Initiative, delivers HIV prevention services
      to high-risk populations at scale. Although the broad costs of such HIV
      interventions are known, to-date there has been little data available on the
      comparative costs of reaching different target groups, including female sex
      workers (FSWs), replace with 'high risk men who have sex with men (HR-MSM) and
      trans-genders. METHODS: Costs are estimated for the first three years of Avahan
      scale up differentiated by typology of female sex workers (brothel, street, home,
      lodge based, bar based), HR-MSM and transgenders in urban districts in India:
      Mumbai and Thane in Maharashtra and Bangalore in Karnataka. Financial and
      economic costs were collected prospectively from a provider perspective. Outputs
      were measured using data collected by the Avahan programme. Costs are presented
      in US$2008. RESULTS: Costs were found to vary substantially by target group. Non
      governmental organisations (NGOs) working with transgender populations had a
      higher mean cost (US $116) per person reached compared to those dealing primarily
      with FSWs (US $75-96) and MSWs (US $90) by the end of year three of the programme
      in Mumbai. The mean cost of delivering the intervention to HR-MSMs (US $42) was
      higher than delivering it to FSWs (US $37) in Bangalore. The package of services
      delivered to each target group was similar, and our results suggest that cost
      variation is related to the target population size, the intensity of the
      programme (in terms of number of contacts made per year) and a number of specific
      issues related to each target group. CONCLUSIONS: Based on our data policy makers
      and program managers need to consider the ease of accessing high risk population
      when planning and budgeting for HIV prevention services for these populations and
      avoid funding programmes on the basis of target population size alone.

PMID- 22375838
TI  - Free radical metabolism of raloxifene in human liver microsomes.
AB  - Raloxifene was metabolized predominantly by CYP3A4 in human liver microsomes to a
      pair of carbon-carbon (RD1-2) and ether (RD3-4) linked homodimers in an
      nicotinamide adenine dinucleotide phosphate-dependent manner. The major homodimer
      formed by human liver microsomes (RD3) was different from the major homodimer
      formed by peroxidases (RD1). RD1, 3 and 4 were identified by both mass
      spectrometry (MS) and nuclear magnetic resonance (NMR) as symmetrical carbon
      carbon (both carbon 7 from benzo[b]thiopen-6-ol) linked homodimer, asymmetrical
      ether (oxygen from 4-hydroxyphenyl and carbon 7 from benzo[b]thiopen-6-ol) linked
      homodimer and asymmetrical ether (oxygen and carbon 7 from benzo[b]thiopen-6-ol)
      linked homodimer, respectively. The structures of the homodimers RD1, 3 and 4
      provided evidence for free radical metabolism of raloxifene by predominantly
      CYP3A4 in human liver microsomes to oxygen-centered phenoxy radicals from 4
      hydroxyphenyl and benzo[b]thiopen-6-ol moieties. Further delocalization to ortho
      carbon-centered radical was only observed for benzo[b]thiopen-6-ol derived
      phenoxy radical.

PMID- 22375839
TI  - Support needs of mothers who experience postpartum psychosis and their partners.
AB  - OBJECTIVES: To explore the perceived support needs and preferences of women with
      postpartum psychosis and their partners. DESIGN: A multisite, exploratory,
      qualitative descriptive design was used. SETTING AND PARTICIPANTS: A purposive
      sample of nine mothers (Canada, n = 7, United States, n = 2) and eight fathers
      (Canada, n = 7, United States, n = 1) was obtained. METHODS: Data were collected
      through one-on-one, in-depth, semistructured interviews. Inductive thematic
      analysis was used to explore the qualitative transcripts. RESULTS: Couples who
      experienced postpartum psychosis looked to health professionals to provide
      reassurance and information on the illness, its management, and prognosis. The
      quality of support and interactions with staff varied, and participants reported
      difficulty identifying and obtaining professional support upon discharge. All
      participants felt that support groups for postpartum illnesses would help to
      normalize the experience and dissipate feelings of isolation. Participants
      reported that informal support networks provided practical help but were limited
      or hindered recovery and management due to lack of knowledge of the illness.
      Despite feeling overwhelmed and isolated, fathers were reluctant to identify
      their own support needs and struggled to ask for help from professionals and
      their informal support network. CONCLUSION: These findings suggest that clinical
      interventions are needed to address the support needs and aid in the recovery of
      families affected by postpartum psychosis.

PMID- 22375840
TI  - The attentional processes underlying impaired inhibition of threat in anxiety:
      the remote distractor effect.
AB  - The current study explored the proposition that anxiety is associated with
      impaired inhibition of threat. Using a modified version of the remote distractor
      paradigm, we considered whether this impairment is related to attentional capture
      by threat, difficulties disengaging from threat presented within foveal vision,
      or difficulties orienting to task-relevant stimuli when threat is present in
      central, parafoveal and peripheral locations in the visual field. Participants
      were asked to direct their eyes towards and identify a target in the presence and
      absence of a distractor (an angry, happy or neutral face). Trait anxiety was
      associated with a delay in initiating eye movements to the target in the presence
      of central, parafoveal and peripheral threatening distractors. These findings
      suggest that elevated anxiety is linked to difficulties inhibiting task
      irrelevant threat presented across a broad region of the visual field.

PMID- 22375841
TI  - Neuropsychological correlates of insight in obsessive-compulsive disorder.
AB  - OBJECTIVE: There are limited data on neuropsychological correlates of poor
      insight in obsessive-compulsive disorder (OCD). We hypothesize that poor insight
      may be associated with greater impairment in tasks of conflict
      resolution/response inhibition and possibly impairment in a task of verbal
      learning and memory. METHOD: Insight and neuropsychological functions were
      assessed in 150 subjects with DSM-IV OCD. The neuropsychological data of 177
      healthy control subjects were used for comparison. RESULTS: Insight score
      correlated significantly with the Stroop Interference Test for conflict
      resolution/response inhibition (P = 0.002), and showed trends for significance
      with the Controlled Oral Word Association (COWA) average for verbal fluency (P =
      0.021) and delayed recall on the Auditory Verbal Learning Test (AVLT) for verbal
      memory (P = 0.015). On regression analysis, the AVLT delayed recall, the COWA
      average, the Matrix score, the Yale-Brown Obsessive-Compulsive Scale total score,
      and current antipsychotic use emerged as significant predictors of poorer
      insight. CONCLUSION: Poor insight is associated with greater impairments in
      conflict resolution/response inhibition, verbal memory, and fluency. Individuals
      with poorer insight may have difficulty in appropriately processing conflicting
      information, updating their memory with corrective information, and then
      accessing this corrective information to modify their irrational beliefs.

PMID- 22375842
TI  - Conflicts of interest in vaccine safety research.
AB  - Conflicts of interest (COIs) cloud vaccine safety research. Sponsors of research
      have competing interests that may impede the objective study of vaccine side
      effects. Vaccine manufacturers, health officials, and medical journals may have
      financial and bureaucratic reasons for not wanting to acknowledge the risks of
      vaccines. Conversely, some advocacy groups may have legislative and financial
      reasons to sponsor research that finds risks in vaccines. Using the vaccine
      autism debate as an illustration, this article details the conflicts of interest
      each of these groups faces, outlines the current state of vaccine safety
      research, and suggests remedies to address COIs. Minimizing COIs in vaccine
      safety research could reduce research bias and restore greater trust in the
      vaccine program.

PMID- 22375843
TI  - The vanishing physician scientist: a critical review and analysis.
AB  - Review of the concept of "the vanishing physician-scientist" shows: 1) medical
      school admissions reject most students wanting medical research careers; 2)
      college years before medical school are the best time for students to begin
      research; 3) efforts to entice admitted medical students and residents to do
      research are too little too late, yielding people not equipped to compete for
      grants with PhD track peers and less motivated because they have clinical careers
      to fall back on; 4) the MD/PhD could be replaced by the PhD/MD with uninterrupted
      research: a full PhD in parallel with part-time medical school followed by part
      time residencies. Supplemental materials are available for this article. Go to
      the publisher's online edition of Accountability in Research to view the free
      supplemental file.

PMID- 22375844
TI  - Infusing research integrity principles and practices into a regional master's
      degree-intensive university: a case study.
AB  - The need for institutions of higher education to advance research and scholarly
      integrity across graduate degree programs involves a strong commitment from each
      institution to develop a comprehensive approach for promoting responsible conduct
      of research (RCR). In response to this need, one master's-intensive regional
      university implemented a three-tier model project (focusing, developing, and
      evaluating/sustaining) for infusing research integrity principles and practices
      while promoting RCR. Components of the model and implementation strategies are
      presented as a case study analysis. Implications of the model for promoting the
      RCR are projected relative to graduate programs focused on applied research.

PMID- 22375845
TI  - Pyrrolidinyl peptide nucleic acid homologues: effect of ring size on
      hybridization properties.
AB  - The effect of ring size of four- to six-membered cyclic beta-amino acid on the
      hybridization properties of pyrrolidinyl peptide nucleic acid with an alternating
      alpha/beta peptide backbone is reported. The cyclobutane derivatives (acbcPNA)
      show the highest T(m) and excellent specificity with cDNA and RNA.

PMID- 22375846
TI  - The hydrogen catalyst cobaloxime: a multifrequency EPR and DFT study of
      cobaloxime's electronic structure.
AB  - Solar fuels research aims to mimic photosynthesis and devise integrated systems
      that can capture, convert, and store solar energy in the form of high-energy
      molecular bonds. Molecular hydrogen is generally considered an ideal solar fuel
      because its combustion is essentially pollution-free. Cobaloximes rank among the
      most promising earth-abundant catalysts for the reduction of protons to molecular
      hydrogen. We have used multifrequency EPR spectroscopy at X-band, Q-band, and D
      band combined with DFT calculations to reveal electronic structure and establish
      correlations among the structure, surroundings, and catalytic activity of these
      complexes. To assess the strength and nature of ligand cobalt interactions, the
      BF(2)-capped cobaloxime, Co(dmgBF(2))(2), was studied in a variety of different
      solvents with a range of polarities and stoichiometric amounts of potential
      ligands to the cobalt ion. This allows the differentiation of labile and strongly
      coordinating axial ligands for the Co(II) complex. Labile, or weakly
      coordinating, ligands such as methanol result in larger g-tensor anisotropy than
      strongly coordinating ligands such as pyridine. In addition, a coordination
      number effect is seen for the strongly coordinating ligands with both singly
      ligated LCo(dmgBF(2))(2) and doubly ligated L(2)Co(dmgBF(2))(2) . The presence of
      two strongly coordinating axial ligands leads to the smallest g-tensor
      anisotropy. The relevance of the strength of the axial ligand(s) to the catalytic
      efficiency of Co(dmgBF(2))(2) is discussed. Finally, the influence of molecular
      oxygen and formation of Co(III) superoxide radicals LCo(dmgBF(2))(2)O(2)(*) is
      studied. The experimental results are compared with a comprehensive set of DFT
      calculations on Co(dmgBF(2))(2) model systems with various axial ligands.
      Comparison with experimental values for the "key" magnetic parameters such as g
      tensor and (59)Co hyperfine coupling tensor allows the determination of the
      conformation of the axially ligated Co(dmgBF(2))(2) complexes. The data presented
      here are vital for understanding the influence of solvent and ligand coordination
      on the catalytic efficiency of cobaloximes.

PMID- 22375847
TI  - Unraveling the chemical composition of caramel.
AB  - Caramel is one of mankind's best known dietary materials obtained from
      carbohydrates by heating. Much effort has been expended toward the chemical
      characterization of the components of caramel but impeded by a lack of suitable
      analytical techniques sufficiently powerful for providing insight into an
      extraordinarily complex material. This paper reports the characterization of
      caramel formed by heating from glucose, fructose, and saccharose using a
      conceptually novel combination of mass spectrometrical techniques. The analytical
      strategy employed uses high-resolution mass spectrometry (MS) followed by
      targeted liquid chromatography-tandem MS experiments. Caramel is composed from
      several thousand compounds formed by a small number of unselective and
      chemoselective reactions. Caramelization products include oligomers with up to
      six carbohydrate units formed through unselective glycosidic bond formation,
      dehydration products of oligomers losing up to a maximum of eight water
      molecules, hydration products of sugar oligomers, disproportionation products,
      and colored aromatic products.

PMID- 22375849
TI  - Moving with the times.

PMID- 22375848
TI  - Distinct role of subcomplexes of the COPI coat in the regulation of ArfGAP2
      activity.
AB  - COPI vesicles serve for transport of proteins and membrane lipids in the early
      secretory pathway. Their coat protein (coatomer) is a heptameric complex that is
      recruited to the Golgi by the small GTPase Arf1. Although recruited en bloc,
      coatomer can be viewed as a stable assembly of an adaptin-like tetrameric
      subcomplex (CM4) and a trimeric 'cage' subcomplex (CM3). Following recruitment,
      coatomer stimulates ArfGAP-dependent GTP hydrolysis on Arf1. Here, we employed
      recombinant coatomer subcomplexes to study the role of coatomer components in the
      regulation of ArfGAP2, an ArfGAP whose activity is strictly coatomer-dependent.
      Within CM4, we define a novel hydrophobic pocket for ArfGAP2 interaction on the
      appendage domain of gamma1-COP. The CM4 subcomplex (but not CM3) is recruited to
      membranes through Arf1 and can subsequently recruit ArfGAP2. Neither CM3 nor CM4
      in itself is effective in stimulating ArfGAP2 activity, but stimulation is
      regained when both subcomplexes are present. Our findings point to a distinct
      role of each of the two coatomer subcomplexes in the regulation of ArfGAP2
      dependent GTP hydrolysis on Arf1, where the CM4 subcomplex functions in GAP
      recruitment, while, similarly to the COPII system, the cage-like CM3 subcomplex
      stimulates the catalytic reaction.

PMID- 22375850
TI  - Identifying the latent failures underpinning medication administration errors: an
      exploratory study.
AB  - OBJECTIVES: The primary aim of this article was to identify the latent failures
      that are perceived to underpin medication errors. STUDY SETTING: The study was
      conducted within three medical wards in a hospital in the United Kingdom. STUDY
      DESIGN: The study employed a cross-sectional qualitative design. DATA COLLECTION
      METHODS: Interviews were conducted with 12 nurses and eight managers. Interviews
      were transcribed and subject to thematic content analysis. A two-step inter-rater
      comparison tested the reliability of the themes. PRINCIPAL FINDINGS: Ten latent
      failures were identified based on the analysis of the interviews. These were ward
      climate, local working environment, workload, human resources, team
      communication, routine procedures, bed management, written policies and
      procedures, supervision and leadership, and training. The discussion focuses on
      ward climate, the most prevalent theme, which is conceptualized here as
      interacting with failures in the nine other organizational structures and
      processes. CONCLUSIONS: This study is the first of its kind to identify the
      latent failures perceived to underpin medication errors in a systematic way. The
      findings can be used as a platform for researchers to test the impact of
      organization-level patient safety interventions and to design proactive error
      management tools and incident reporting systems in hospitals.

PMID- 22375851
TI  - Diaminogermylene and diaminostannylene derivatives of gold(I): novel AuM and AuM2
      (M = Ge, Sn) complexes.
AB  - The reactions of [AuCl(THT)] (THT = tetrahydrothiophene) with 1 equiv of the
      group 14 diaminometalenes M(HMDS)(2) [M = Ge, Sn; HMDS = N(SiMe(3))(2)] lead to
      [Au{MCl(HMDS)(2)}(THT)] [M = Ge (1), Sn (2)], which contain a metalate(II) ligand
      that arises from insertion of the corresponding M(HMDS)(2) reagent into the Au-Cl
      bond of the gold(I) reagent. While compound 1 reacts with more Ge(HMDS)(2) to
      give the germanate-germylene derivative [Au{GeCl(HMDS)(2)}{Ge(HMDS)(2)}] (3),
      which results from substitution of Ge(HMDS)(2) for the THT ligand of 1, an
      analogous treatment of compound 2 with Sn(HMDS)(2) gives the stannate-stannylene
      derivative [Au{SnCl(HMDS)(2)}{Sn(HMDS)(2)(THT)}] (4), which has a THT ligand
      attached to the stannylene tin atom and which, in solution at room temperature,
      participates in a dynamic process that makes its two Sn(HMDS)(2) fragments
      equivalent (on the NMR time scale). A similar dynamic process has not been
      observed for the AuGe(2) compound 3 or for the AuSn(2) derivatives
      [Au{SnR(HMDS)(2)}{Sn(HMDS)(2)(THT)}] [R = Bu (5), HMDS (6)], which have been
      prepared by treating complex 4 with LiR. The structures of compounds 1 and 3-6
      have been determined by X-ray diffraction.

PMID- 22375853
TI  - Aripiprazole in children with Tourette's disorder and co-morbid attention
      deficit/hyperactivity disorder: a 12-week, open-label, preliminary study.
AB  - Tourette's disorder (TD) in children and adolescents is frequently co-morbid with
      attention-deficit/hyperactivity disorder (ADHD). Dopamine-blockers are the first
      line treatment for TD, whereas dopamine-agonists, such as stimulants, are the
      gold-standard in the treatment of ADHD. These contrasting effects supported
      concerns about the risk that stimulants for treating ADHD may trigger or worsen
      co-morbid tics. Aripiprazole, a partial dopamine agonist, acts as an antagonist
      at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist
      properties under hypodopaminergic conditions. The present study describes the use
      of aripiprazole (10.0 +/- 4.8 mg/day) in a consecutive group of 28 patients with
      a primary diagnosis of TD and co-morbid ADHD, combined subtype. The Yale Global
      Tic Severity Scale (YGTSS) and the ADHD-Rating Scale (ADHD-RS-IV) were used as
      primary outcome measures and both significantly improved (p<0.001) after the
      treatment. Global measures of severity (Clinical Global Impressions-Severity) and
      of functional impairment (Children's Global Assessment Scale) also significantly
      improved during the treatment (p<0.001). At the YGTSS there was a reduction of
      42.5%, in motor tics, of 47.9% in phonic tics (44.7% for the combined scores),
      and of 32.3% in tic impairment. Nineteen patients (67.9%) had a reduction of at
      least 50% of the YGTSS score (motor+phonic tics). The improvement at the ADHD-RS
      IV score was 22.5%, 12 patients (42.8%) presented an improvement of 30%, but only
      2 (7.1%) an improvement greater than 50%. Using a logistic regression model, a
      reduction of at least 30% in ADHD-RS-IV score was more likely to occur in the
      obsessive-compulsive disorder co-morbid group. Aripiprazole was well tolerated
      and none of the patients discontinued medication because of side effects. In
      summary, aripiprazole resulted in an effective treatment for TD, but it was only
      moderately effective on co-occurring ADHD symptomatology. Our preliminary data
      suggest that aripiprazole may represent a possible therapeutic option, among
      other possible monotherapies addressing both tics and ADHD.

PMID- 22375854
TI  - A preliminary investigation of corpus callosum and anterior commissure
      aberrations in aggressive youth with bipolar disorders.
AB  - OBJECTIVE: Although behavioral deficits in bipolar disorder (BPD) are well
      described, the specific brain white matter (WM) disruptions have not been
      completely characterized, and neural mechanisms underlying dysfunction in BPD are
      not well established, particularly for youth with BPD and aggression. This
      preliminary study utilized diffusion tensor imaging (DTI) to investigate
      commissural tracts (corpus callosum [CC] and anterior commissure [AC]) in youth
      with BPD, because disruption of interhemispheric communication may contribute to
      the emotional deficits that are characteristic of the illness. METHOD: DTI was
      used to investigate WM in 10 youth (7-17 years of age) with BPD and 10 typically
      developing age-matched controls. Tract-based spatial statistics voxel-wise
      analysis was used to compare fractional anisotropy (FA) of the two groups. We
      specifically focused on five subdivisions of the midsagittal CC as well as on the
      decussation of AC, which connects the temporal lobes. Exploratory correlations
      between FA values and life history of aggression scores were calculated for the
      BPD group. RESULTS: Youth with BPD had significantly lower FA values in the
      callosal genu and AC. FA values in the AC were negatively correlated with a life
      history of aggression in the BPD group. CONCLUSIONS: These results contribute to
      a growing literature implicating a role for the genu of the CC in BPD and are the
      first to report WM variations in the AC of children with BPD. Taken together with
      the correlational data for aggression and the role of the AC in emotional
      processing, our data provide preliminary evidence for a possible association
      between the structural integrity of the WM of the AC and aggression in pediatric
      BPD.

PMID- 22375855
TI  - Presentation and treatment of acute psychosis in an adolescent girl with cerebral
      palsy.

PMID- 22375856
TI  - Health services reform in Bangladesh: hearing the views of health workers and
      their professional bodies.
AB  - BACKGROUND: In Bangladesh, widespread dissatisfaction with government health
      services did not improve during the Health and Population Sector Programme (HPSP)
      reforms from 1998-2003. A 2003 national household survey documented public and
      health service users' views and experience. Attitudes and behaviour of health
      workers are central to quality of health services. To investigate whether the
      views of health workers influenced the reforms, we surveyed local health workers
      and held evidence-based discussions with local service managers and professional
      bodies. METHODS: Some 1866 government health workers in facilities serving the
      household survey clusters completed a questionnaire about their views,
      experience, and problems as workers. Field teams discussed the findings from the
      household and health workers' surveys with local health service managers in five
      upazilas (administrative sub-districts) and with the Bangladesh Medical
      Association (BMA) and Bangladesh Nurses Association (BNA). RESULTS: Nearly one
      half of the health workers (45%) reported difficulties fulfilling their duties,
      especially doctors, women, and younger workers. They cited inadequate supplies
      and infrastructure, bad behaviour of patients, and administrative problems. Many,
      especially doctors (74%), considered they were badly treated as employees. Nearly
      all said lack of medicines in government facilities was due to inadequate supply,
      not improved during the HPSP. Two thirds of doctors and nurses complained of bad
      behaviour of patients. A quarter of respondents thought quality of service had
      improved as a result of the HPSP.Local service managers and the BMA and BNA
      accepted patients had negative views and experiences, blaming inadequate
      resources, high patient loads, and patients' unrealistic expectations. They said
      doctors and nurses were demotivated by poor working conditions, unfair treatment,
      and lack of career progression; private and unqualified practitioners sought to
      please patients instead of giving medically appropriate care. The BMA considered
      it would be dangerous to attempt to train and register unqualified practitioners.
      CONCLUSIONS: The continuing dissatisfaction of health workers may have undermined
      the effectiveness of the HPSP. Presenting the views of the public and service
      users to health managers helped to focus discussions about quality of services.
      It is important to involve health workers in health services reforms.

PMID- 22375852
TI  - Oxytocin and vasopressin agonists and antagonists as research tools and potential
      therapeutics.
AB  - We recently reviewed the status of peptide and nonpeptide agonists and
      antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin
      (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we
      update the status of peptides and nonpeptides as: (i) research tools and (ii)
      therapeutic agents. We also present our recent findings on the design of
      fluorescent ligands for V(1b) receptor localisation and for OT receptor
      dimerisation. We note the exciting discoveries regarding two novel naturally
      occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a
      selective OT agonist point to the continued therapeutic potential of peptides in
      this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan
      and the V(2) antagonist tolvaptan have received Food and Drug Administration
      approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and
      V(2) antagonists and OT agonists and antagonists has recently been abandoned by
      Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at
      Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of
      premature labour. A number of the nonpeptide ligands that were not successful in
      clinical trials are proving to be valuable as research tools. Peptide agonists
      and antagonists continue to be very widely used as research tools in this field.
      In this regard, we present receptor data on some of the most widely used peptide
      and nonpeptide ligands, as a guide for their use, especially with regard to
      receptor selectivity and species differences.

PMID- 22375858
TI  - Mechanism of a redox coupling of seleninic acid with thiol.
AB  - Equimolar quantities of 2-ethoxyethaneseleninic acid and p-thiocresol react
      rapidly in dichloromethane solution to give the selenosulfide along with
      disulfide, diselenide, and two products oxidized at sulfur, the thiosulfonate and
      the selenosulfonate. The latter two are new for this sort of coupling; their
      formation may be the result of an early thioseleninate to selenosulfinate
      isomerization. A radical chain mechanism is proposed to account for all five
      products, as well as their relative amounts.

PMID- 22375859
TI  - Effects of oral finasteride on erectile function in a rat model.
AB  - INTRODUCTION: Many clinical studies reported finasteride-related erectile
      dysfunction, but to date, few animal experiments have focused on it. AIM: To
      investigate the effects of oral finasteride on erectile function in a rat model.
      MAIN OUTCOME MEASURES: Erectile responses and morphological changes. METHODS:
      Adult, male Sprague-Dawley rats were divided into four groups (25/group): (i)
      control; (ii) castration; (iii) castration with testosterone (T) replacement; and
      (iv) oral finasteride treatment. Four weeks later, erectile function was measured
      by the ratio of intracavernosal pressure and mean arterial blood pressure upon
      electrical stimulation of the cavernous nerve. Serum T and dihydrotestosterone
      (DHT) and intraprostatic DHT were measured. The weights and histopathological
      features of the penile corpus cavernosum and prostate were examined. RESULTS:
      Serum T and DHT and intraprostatic DHT concentrations, erectile function, and
      mean weights of the corpus cavernosum and prostate were lowest in group 2. There
      was no significant difference in the serum T concentration and erectile function
      between groups 4 and 1. However, the serum and intraprostatic DHT concentrations
      were significantly lower in group 4 than in group 1 (both P < 0.001). The tissue
      weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in
      group 4 compared with group 1 (both P < 0.001). Histopathology revealed a
      significant atrophy of the prostate in groups 2 and 4. There was a significant
      decrease in the smooth muscle content in group 2, but not in groups 3 and 4.
      CONCLUSIONS: In a rat model, finasteride treatment for 4 weeks reduces the weight
      of the corpus cavernosum but appears not to affect the erectile responses to
      electrical stimulation of the cavernous nerve. As erection is a complex process
      involving important signaling in the brain, further studies are necessary to
      demonstrate the long-term effects of finasteride on both central and peripheral
      neural pathways of erection.

PMID- 22375861
TI  - Ecological studies of the bio-inoculant Trichoderma hamatum LU592 in the root
      system of Pinus radiata.
AB  - The plant health- and growth-promoting biological inoculant (bio-inoculant)
      Trichoderma hamatum LU592 was transformed with the constitutively expressed green
      fluorescent protein (gfp) and hygromycin B resistance (hph) genes to specifically
      monitor the isolate in the root system of Pinus radiata within a strong
      indigenous Trichoderma population. A modified dilution plating technique was
      developed to allow the determination of the mycelia proportion of total propagule
      levels. LU592 was shown to colonize the rhizosphere most effectively when 10(5) 
      spores per pot were applied compared with inoculum concentrations of 10(3)  and
      10(7)  spores per pot. LU592 extended its zone of activity beyond the rhizosphere
      to at least 1 cm away from the root surface. A positive relationship was shown
      between P. radiata root maturation and the spatial and temporal proliferation of
      LU592 in the root system. A steep increase in mycelia levels and proportion of
      penetrated root segments was observed after 12 weeks. This study reinforces the
      value of genetic markers for use in ecological studies of filamentous fungi.
      However, despite isolate-specific recovery of the introduced isolate, it was
      shown that total propagule counts do not always correlate with the amount of
      viable mycelium present in the root system. Therefore, it is proposed that the
      differentiation of mycelia from spores and root penetration is used as more
      accurate measures of fungal activity.

PMID- 22375860
TI  - Eye movement impairments in Parkinson's disease: possible role of
      extradopaminergic mechanisms.
AB  - BACKGROUND: The basal ganglia (BG) are thought to play an important role in the
      control of eye movements. Accordingly, the broad variety of subtle oculomotor
      alterations that has been described in Parkinson's disease (PD) are generally
      attributed to the dysfunction of the BG dopaminergic system. However, the present
      study suggest that dopamine substitution is much less effective in improving
      oculomotor performance than it is in restoring skeletomotor abilities. METHODS:
      We investigated reactive, visually guided saccades (RS), smooth pursuit eye
      movements (SPEM), and rapidly left-right alternating voluntary gaze shifts (AVGS)
      by video-oculography in 34 PD patients receiving oral dopaminergic medication (PD
      DA), 14 patients with deep brain stimulation of the nucleus subthalamicus (DBS
      STN), and 23 control subjects (CTL);In addition, we performed a thorough review
      of recent literature according therapeuthic effects on oculomotor performance in
      PD by switching deep brain stimulation off and on in the PD-DBS patients, we
      achieved swift changes between their therapeutic states without the delays of
      dopamine withdrawal. In addition, participants underwent neuropsychological
      testing. RESULTS: Patients exhibited the well known deficits such as increased
      saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS.
      Across patients none of the investigated oculomotor parameters correlated with
      UPDRS III whereas there was a negative correlation between SPEM gain and
      susceptibility to interference (Stroop score). Of the observed deficiencies, DBS
      STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS
      performance. CONCLUSIONS: We conclude that the impairment of SPEM in PD results
      from a cortical, conceivably non-dopaminergic dysfunction, whereas patients'
      difficulty to rapidly execute AVGS might be related to their BG dysfunction.

PMID- 22375865
TI  - Cichorins B and C: two new benzo-isochromenes from Cichorium intybus.
AB  - Two new benzo-isochromenes, named cichorins B (1) and C (2), were isolated from
      Cichorium intybus. The structures of the new compounds were elucidated by
      detailed spectroscopic analysis such as 1H, 13C NMR, COSY, HMQC, HMBC, and HR-EI
      MS. Relative configurations of asymmetric centers of cichorins B and C were
      determined by the analysis of the 1H NMR coupling constants together with the 2D
      NOESY and 1D NOE experiments as well as from [alpha]25(D) value.

PMID- 22375862
TI  - Tandem repeat markers as novel diagnostic tools for high resolution
      fingerprinting of Wolbachia.
AB  - BACKGROUND: Strains of the endosymbiotic bacterium Wolbachia pipientis are
      extremely diverse both genotypically and in terms of their induced phenotypes in
      invertebrate hosts. Despite extensive molecular characterisation of Wolbachia
      diversity, little is known about the actual genomic diversity within or between
      closely related strains that group tightly on the basis of existing gene marker
      systems, including Multiple Locus Sequence Typing (MLST). There is an urgent need
      for higher resolution fingerprinting markers of Wolbachia for studies of
      population genetics, horizontal transmission and experimental evolution. RESULTS:
      The genome of the wMel Wolbachia strain that infects Drosophila melanogaster
      contains inter- and intragenic tandem repeats that may evolve through expansion
      or contraction. We identified hypervariable regions in wMel, including intergenic
      Variable Number Tandem Repeats (VNTRs), and genes encoding ankyrin (ANK) repeat
      domains. We amplified these markers from 14 related Wolbachia strains belonging
      to supergroup A and were successful in differentiating size polymorphic alleles.
      Because of their tandemly repeated structure and length polymorphism, the markers
      can be used in a PCR-diagnostic multilocus typing approach, analogous to the
      Multiple Locus VNTR Analysis (MLVA) established for many other bacteria and
      organisms. The isolated markers are highly specific for supergroup A and not
      informative for other supergroups. However, in silico analysis of completed
      genomes from other supergroups revealed the presence of tandem repeats that are
      variable and could therefore be useful for typing target strains. CONCLUSIONS:
      Wolbachia genomes contain inter- and intragenic tandem repeats that evolve
      through expansion or contraction. A selection of polymorphic tandem repeats is a
      novel and useful PCR diagnostic extension to the existing MLST typing system of
      Wolbachia, as it allows rapid and inexpensive high-throughput fingerprinting of
      closely related strains for which polymorphic markers were previously lacking.

PMID- 22375863
TI  - A dose-response relationship between exposure to a large-scale HIV preventive
      intervention and consistent condom use with different sexual partners of female
      sex workers in southern India.
AB  - BACKGROUND: The Avahan Initiative, a large-scale HIV preventive intervention
      targeted to high-risk populations including female sex workers (FSWs), was
      initiated in 2003 in six high-prevalence states in India, including Karnataka.
      This study assessed if intervention exposure was associated with condom use with
      FSWs' sexual partners, including a dose-response relationship. METHODS: Data were
      from a cross-sectional study (2006-07) of 775 FSWs in three districts in
      Karnataka. Survey methods accounted for the complex cluster sampling design.
      Bivariate and multivariable logistic regression was used to separately model the
      relationships between each of five intervention exposure variables and five
      outcomes for consistent condom use (CCU= always versus
      frequently/sometimes/never) with different sex partners, including with: all
      clients; occasional clients; most recent repeat client; most recent non-paying
      partner; and the husband or cohabiting partner. Linear tests for trends were
      conducted for three continuous intervention exposure variables. RESULTS: FSWs
      reported highest CCU with all clients (81.7%); CCU was lowest with FSWs' husband
      or cohabiting partner (9.6%). In multivariable analysis, the odds of CCU with all
      clients and with occasional clients were 6.3-fold [95% confidence intervals, CIs:
      2.8-14.5] and 2.3-fold [95% CIs: 1.4-4.1] higher among FSWs contacted by
      intervention staff and 4.9-fold [95% CIs: 2.6-9.3] and 2.3-fold [95% CIs: 1.3
      4.1] higher among those who ever observed a condom demonstration by staff,
      respectively, compared to those who had not. A significant dose-response
      relationship existed between each of these CCU outcomes and increased duration
      since first contacted by staff (P=0.001; P=0.006) and numbers of condom
      demonstrations witnessed (P=0.004; P=0.026); a dose-response relationship was
      also observed between condom use with all clients and number of times contacted
      by staff (P=0.047). Intervention exposure was not associated with higher odds of
      CCU with the most recent repeat client, most recent non-paying partner or with
      the husband or cohabiting partner. CONCLUSION: Study findings suggest that
      exposure to a large-scale HIV intervention for FSWs was associated with increased
      CCU with commercial clients. Moreover, there were dose-response relationships
      between CCU with clients and increased duration since first contacted by staff,
      times contacted by staff and number of condom demonstrations. Additional program
      effort is required to increase condom use with non-commercial partners.

PMID- 22375866
TI  - New steroidal glycoside ester and aliphatic acid from the fruits of Lycium
      chinense.
AB  - Two new compounds stigmast-5-en-3beta-ol-3-O-beta-D-(2'-n-triacontanoyl)
      glucopyranoside (1) and 19,21-dimethyl triacont-17,22,24,26,28-pentaene-1-oic
      acid (2), along with the three known compounds n-tetracosanyl octadec-9-enoate
      (3), beta-sitosterol, and beta-sitosterol-3-O-beta-D-glucoside, have been
      isolated from the methanol extract of Lycium chinense fruits. The structures of
      these phytoconstituents have been established on the basis of spectral data
      analysis and chemical reactions.

PMID- 22375867
TI  - Two new triterpenoid saponins from the leaves of Ilex kudingcha.
AB  - Two new triterpene saponins, ilekudinchosides F (1) and G (2), along with three
      known saponins were isolated from the leaves of Ilex kudingcha C. J. Tseng. The
      new compounds were characterized as 3beta,19alpha-dihydroxy-12alpha-ethoxy-urs
      13(18)-ene-28,20beta-lactone-3-O-[beta-D-glucopyranosyl(1 -> 3)]-[alpha-L
      rhamnopyranosyl(1 -> 2)]-alpha-L-arabinopyranoside (1) and 3beta,19alpha
      dihydroxy-12alpha-methoxy-urs-13(18)-ene-28,20beta-lactone-3-O-[alpha-L
      rhamnopyranosyl(1 -> 2)]-alpha-L-arabinopyranoside (2). The new structures were
      elucidated by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD
      spectrometry, and the known compounds were identified by the comparison of their
      NMR and HR-TOF-MS data with those reported in the literature.

PMID- 22375868
TI  - The synthesis of pennogenin 3-O-beta-D-glucopyranosyl-(1 -> 3)-[alpha-L
      rhamnopyranosyl-(1 -> 2)]-beta-D-glucopyranoside.
AB  - Pennogenin 3-O-beta-D-glucopyranosyl-(1 -> 3)-[alpha-L-rhamnopyranosyl-(1 -> 2)]
      beta-D-glucopyranoside, a monodesmosidic saponin isolated from Paris polyphylla
      Smith var. yunnanensis with promised antitumor activities, was firstly
      synthesized from glucoside thiol via nine steps and with 27% overall yield.

PMID- 22375869
TI  - Total synthesis of 6'-hydroxyjusticidin A.
AB  - The first total synthesis of 6'-hydroxyjusticidin A, isolated from Justicia
      procumbens L. with good inhibitory activity against cancer cells, has been
      accomplished. The structure was confirmed by 1H NMR, 13C NMR, and HR-ESI-MS. The
      key steps involved a Diels-Alder cycloaddition reaction and a reduction in NaBH4.

PMID- 22375870
TI  - Two new saponins from Thalictrum fortunei.
AB  - Two new cycloartane glycosides were isolated from the aerial parts of Thalictrum
      fortunei (Ranunculaceae). The chemical structures of these compounds were
      elucidated as 3-O-beta-D-glucopyranosyl (1 -> 4)-beta-d-fucopyranosyl-(22S,24Z)
      cycloart-24-en-3beta,22,26,30-tetraol 26-O-beta-D-glucopyranoside and 3-O-beta-D
      glucopyranosyl (1 -> 4)-beta-D-fucopyranosyl-(22S,24Z)-cycloart-24-en
      3beta,22,26,29-tetraol 26-O-beta-D-glucopyranoside by extensive 1D and 2D NMR
      methods, HR-ESI-MS, and hydrolysis. Their cytotoxic activities toward human
      hepatoma Bel-7402 cells, human colon carcinoma LoVo cells, and human non-small
      cell lung cancer NCIH-460 cells were evaluated by MTT assay, respectively.

PMID- 22375871
TI  - New triterpenoid saponins from Patrinia scabiosifolia.
AB  - Phytochemical investigation of methanol extract from the whole plants of Patrinia
      scabiosifolia Fisch. resulted in the isolation of three new triterpenoid saponins
      (1-3) along with twelve known triterpenoids (4-15). The structures of the new
      compounds were established as 11alpha, 12alpha-epoxy-3-O-beta-D-xylopyranosyl
      olean-28, 13beta-olide (1), 11alpha, 12alpha-epoxy-3-O-beta-D-xylopyranosyl-(1 ->
      3)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-xylopyranosyl-olean-28, 13beta-olide
      (2), and 3-O-beta-D-xylopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-beta
      D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranoside (3) on the basis of
      various spectroscopic analyses (including different 1D and 2D NMR spectroscopies
      and high-resolution electrospray ionization mass spectrometry) and chemical
      evidences.

PMID- 22375872
TI  - Two new compounds from the fruits of Buddleja lindleyana with neuroprotective
      effect.
AB  - Two new triterpenoid glycosides, mimengosides H (1) and I (2), were isolated from
      the fruits of Buddleja lindleyana Fort. Their structures were determined by
      extensive spectroscopic methods. Neuroprotective effects of these isolates
      against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells were
      evaluated. Pretreatment with compound 1 had potential protective effect in a
      concentration range from 0.1 to 1 MUmol l-1.

PMID- 22375873
TI  - Four new triterpenoids from the leaves of Psidium guajava.
AB  - Four new triterpenoids, psiguanins A-D (1-4), along with 13 known ones (5-17),
      were isolated from the leaves of Psidium guajava. The structures of new compounds
      were determined as 2alpha,3beta-dihydroxy-taraxer-20-en-28-oic acid (1),
      2alpha,3beta,12alpha,13beta-tetrahydroxy-urs-28-oic acid (2),
      2alpha,3beta,12beta,13beta-tetrahydroxy-urs-28-oic acid (3), and
      2alpha,3beta,12beta,13alpha-tetrahydroxy-urs-28-oic acid (4), respectively, on
      the basis of comprehensive spectroscopic methods and molecular modeling
      calculation. Among them, compound 4 was characterized as an unusual ursane-type
      triterpenoid with cis-fused C/D ring system.

PMID- 22375874
TI  - Synthesis and biological evaluation of oleanolic acid derivatives as antitumor
      agents.
AB  - Derivatives of oleanolic acid were synthesized and evaluated in vitro for their
      growth inhibition against human hepatocellular carcinoma cell line (HepG2) and
      colon cancer cell line (Col-02). Several derivatives exhibited moderate-to-good
      inhibitory activity, with 3 displaying the most promising inhibition [GI50 = 1.75
      MUM (HepG2), 0.71 MUM (Col-02)]. Structure-activity relationship analyses of
      these derivatives demonstrated that a 1-en-2-cyano-3-oxo in ring A and a nitro at
      C-17 were important in retention of the inhibition against HepG2 and Col-02
      cells.

PMID- 22375875
TI  - Dibenzocyclooctadiene lignans from Kadsura coccinea.
AB  - In vitro anti-allergic screening of medicinal herbal extracts revealed that the
      EtOAc extract of the rhizoma of Kadsura coccinea inhibited nitric oxide (NO)
      production in a lipopolysaccharide and recombinant mouse interferon-gamma
      activated murine macrophage-like cell line, RAW264.7. Further fractionation of
      the EtOAc extract led to the isolation of two new dibenzocyclooctadiene lignans
      kadsuralignan G (1) and kadsuralignan L (2), and three known analog compounds.
      The absolute stereostructures were established by circular dichroism spectra.
      Both 1 and 2 showed moderate NO production inhibitory activities.

PMID- 22375876
TI  - Simultaneous determination and pharmacokinetic analysis of seven alkaloids and
      two flavonoids from rat plasma by HPLC-DAD after oral administration of Wuzhuyu
      decoction.
AB  - A simple and sensitive high-performance liquid chromatographic method was
      developed for the simultaneous determination and pharmacokinetic analysis of
      seven alkaloids dehydroevodiamine (DHED), 10-hydroxyrutaecarpine (HDR),
      evodiamine (EDM), rutaecarpine (RCP), 1-methyl-2-n-nonyl-4(1H)quinolone (MNQ),
      evocarpine (ECP), and dihydroevocarpine (DHE), and two flavonoids isorhamnetin-7
      O-rutinoside (RIM) and diosmetin-7-O-beta-d-glucopyranoside (GRD) in rat plasma
      after oral administration of Wuzhuyu decoction. The flow rate was kept at 1.0
      ml/min and the detection wavelength was set at 300 nm. The calibration curves
      were linear in the range of 0.5013-30.076 MUg/ml for DHED, 0.2161-21.608 MUg/ml
      for RIM, 0.161-12.876 MUg/ml for HDR, 0.2146-21.457 MUg/ml for GRD, 2.0464-40.928
      MUg/ml for EDM, 1.0398-31.194 MUg/ml for RCP, 0.5970-35.818 MUg/ml for MNQ,
      0.8371-20.928 MUg/ml for ECP, and 0.5167-31.003 MUg/ml for DHE. The precision
      (relative standard deviation (RSD), %) for all was less than 10% and the accuracy
      (relative error (RE), %) was within +/- 10%. The results demonstrated that the
      assay had remarkable reproducibility with acceptable accuracy and precision. The
      lower limit of quantifications for the compounds in plasma ranged from 0.12 to
      0.23 MUg/ml and the lower limit of detections ranged from 0.024 to 0.076 MUg/ml.
      This validated method has been successfully applied in the pharmacokinetics study
      of seven alkaloids and two flavonoids after orally administrating the Wuzhuyu
      decoction to rats.

PMID- 22375877
TI  - Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal
      CYP450 enzyme activities in vitro and in vivo.
AB  - Capsaicin and dihydrocapsaicin, the two most abundant members of capsaicinoids in
      chili peppers, are widely used as food additives and for other purposes. In this
      study, we examined the inhibitory potentials of capsaicin and dihydrocapsaicin
      against CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 activities in human
      liver microsomes. The effects of these two capsaicinoids on CYP450 enzymes were
      also evaluated in vivo in rats. The results demonstrated that capsaicin and
      dihydrocapsaicin moderately inhibited five isozymes (IC50) values ranging from
      4.4 to 61.8 MUM), with the exception of CYP2E1 (IC50 > 200 MUM). Both
      capsaicinoids exhibited competitive, mixed, and noncompetitive inhibition on
      these isozymes (K (i) = 3.1 +/- 0.5 - 78.6 +/- 8.4 MUM). Time-dependent
      inhibition of CYP3A4/5 by capsaicin was found. After multiple administrations of
      capsaicin and dihydrocapsaicin (1, 4, and 10 mg/kg) to rats, chlorzoxazone 6
      hydroxylase activity and the expression of CYP2E1 were increased in liver
      microsomes. Our findings indicated that the possibility of food-drug interactions
      mediated by capsaicin and dihydrocapsaicin could not be excluded, and provided
      the useful information for evaluating the anticarcinogenic potentials of these
      two capsaicinoids.

PMID- 22375878
TI  - Lignans from Syringa pinnatifolia Hemsl. Var. alashanensis.
AB  - Two new lignans, syripinnalignans A and B (1 and 2), together with two known
      lignans, were isolated from the stem of Syringa pinnatifolia Hemsl. Var.
      alashanensis. The structures of 1 and 2 were elucidated by spectroscopic methods,
      including extensive 1D and 2D NMR techniques.

PMID- 22375879
TI  - A new biflavonoid with antiviral activity from the roots of Wikstroemia indica.
AB  - A new biflavonoid, 4'-methoxydaphnodorin E, was isolated from the antiviral
      fraction of Wikstroemia indica against respiratory syncytial virus (RSV). Its
      structure was determined on the basis of extensive spectroscopic data including
      HR-ESI-MS and 2D NMR. The biflavonoid was tested for its in vitro anti-RSV
      activity with cytopathic effect (CPE) reduction assay, and displayed potent
      effect with 50% inhibitory concentration (IC50) value of 2.8 MUM and selective
      index (SI) value of 5.4.

PMID- 22375881
TI  - Biohybrid photosynthetic antenna complexes for enhanced light-harvesting.
AB  - Biohybrid antenna systems have been constructed that contain synthetic
      chromophores attached to 31mer analogues of the bacterial photosynthetic core
      light-harvesting (LH1) beta-polypeptide. The peptides are engineered with a Cys
      site for bioconjugation with maleimide-terminated chromophores, which include
      synthetic bacteriochlorins (BC1, BC2) with strong near-infrared absorption and
      commercial dyes Oregon green (OGR) and rhodamine red (RR) with strong absorption
      in the blue-green to yellow-orange regions. The peptides place the Cys 14 (or 6)
      residues before a native His site that binds bacteriochlorophyll a (BChl-a) and,
      like the native LH proteins, have high helical content as probed by single
      reflection IR spectroscopy. The His residue associates with BChl-a as in the
      native LH1 beta-polypeptide to form dimeric betabeta-subunit complexes [31mer(
      14Cys)X/BChl](2), where X is one of the synthetic chromophores. The native-like
      BChl-a dimer has Q(y) absorption at 820 nm and serves as the acceptor for energy
      from light absorbed by the appended synthetic chromophore. The energy-transfer
      characteristics of biohybrid complexes have been characterized by steady-state
      and time-resolved fluorescence and absorption measurements. The quantum yields of
      energy transfer from a synthetic chromophore located 14 residues from the BChl
      coordinating His site are as follows: OGR (0.30) < RR (0.60) < BC2 (0.90).
      Oligomeric assemblies of the subunit complexes [31mer(-14Cys)X/BChl](n) are
      accompanied by a bathochromic shift of the Q(y) absorption of the BChl-a oligomer
      as far as the 850-nm position found in cyclic native photosynthetic LH2
      complexes. Room-temperature stabilized oligomeric biohybrids have energy-transfer
      quantum yields comparable to those of the dimeric subunit complexes as follows:
      OGR (0.20) < RR (0.80) < BC1 (0.90). Thus, the new biohybrid antennas retain the
      energy-transfer and self-assembly characteristics of the native antenna
      complexes, offer enhanced coverage of the solar spectrum, and illustrate a
      versatile paradigm for the construction of artificial LH systems.

PMID- 22375884
TI  - Iron deficiency affects plant defence responses and confers resistance to Dickeya
      dadantii and Botrytis cinerea.
AB  - Iron is an essential element for most living organisms, and pathogens are likely
      to compete with their hosts for the acquisition of this element. The bacterial
      plant pathogen Dickeya dadantii has been shown to require its siderophore
      mediated iron uptake system for systemic disease progression on several host
      plants, including Arabidopsis thaliana. In this study, we investigated the effect
      of the iron status of Arabidopsis on the severity of disease caused by D.
      dadantii. We showed that symptom severity, bacterial fitness and the expression
      of bacterial pectate lyase-encoding genes were reduced in iron-deficient plants.
      Reduced symptoms correlated with enhanced expression of the salicylic acid
      defence plant marker gene PR1. However, levels of the ferritin coding transcript
      AtFER1, callose deposition and production of reactive oxygen species were reduced
      in iron-deficient infected plants, ruling out the involvement of these defences
      in the limitation of disease caused by D. dadantii. Disease reduction in iron
      starved plants was also observed with the necrotrophic fungus Botrytis cinerea.
      Our data demonstrate that the plant nutritional iron status can control the
      outcome of an infection by acting on both the pathogen's virulence and the host's
      defence. In addition, iron nutrition strongly affects the disease caused by two
      soft rot-causing plant pathogens with a large host range. Thus, it may be of
      interest to take into account the plant iron status when there is a need to
      control disease without compromising crop quality and yield in economically
      important plant species.

PMID- 22375882
TI  - Opioid dependency in pregnancy and length of stay for neonatal abstinence
      syndrome.
AB  - OBJECTIVE: To examine opioid replacement therapy in pregnancy and effect on
      neonatal outcomes, including length of hospital stay for neonatal abstinence
      syndrome. DESIGN: Retrospective descriptive study. SETTING: Labor and delivery
      unit and neonatal intensive care unit (NICU), Eastern Maine Medical Center,
      Bangor, Maine. PARTICIPANTS: One hundred fifty-two opioid-dependent pregnant
      women on methadone maintenance therapy (MMT) (n = 136) or buprenorphine
      maintenance therapy (BMT) (n = 16) during pregnancy and their neonates. The
      neonates were born between January 1, 2005 and December 31, 2007. METHODS: A
      review of the electronic medical record (EMR) was conducted of all opioid
      dependent women who were maintained on MMT or BMT at the time of admission for
      labor and delivery and their neonates. RESULTS: Maternal methadone dose and
      concomitant in-utero exposure to benzodiazepines prolonged the length of hospital
      stay for neonates. Length of stay was shorter in breastfed neonates than formula
      fed neonates or neonates who received formula and breast milk. Neonates with
      prenatal exposure to MMT spent more days in the hospital (21 vs. 14 days) for
      treatment of neonatal abstinence syndrome (NAS) than infants with prenatal
      exposure to BMT. CONCLUSION: These findings are consistent with previous research
      on the simultaneous use of methadone and benzodiazepines during pregnancy and
      provide further direction for the treatment of opioid dependency during
      pregnancy. Harm reduction strategies for opioid-dependent pregnant women in
      substance abuse treatment with MMT may one day include guidance on daily
      treatment doses and recommendations to avoid the concomitant use of
      benzodiazepines to lessen NAS. Breastfeeding should be recommended to shorten
      length of stay. Understanding perinatal and neonatal outcomes of pregnant women
      on methadone or buprenorphine will help to identify optimal treatment for opioid
      dependency in pregnancy.

PMID- 22375885
TI  - Stereochemically versatile synthesis of the C1-C12 fragment of tedanolide C.
AB  - A flexible synthesis of the C1-C12 fragment of Tedanolide C has been accomplished
      in eight steps from 2-methyl-2,4-pentadienal. Asymmetric hydroformylation of a
      1,3-diene allows for the late-stage generation of either C10 epimer with complete
      catalyst control. Diastereoselective addition of an isobutyryl beta-ketoester
      dianion to an alpha,beta-disubstituted chiral aldehyde sets the C5
      stereochemistry while installing the geminal dimethyl unit. Differential
      protection of a syn-1,3-diol is performed as a highly efficient single-pot
      operation.

PMID- 22375886
TI  - Ambulatory subspecialty visits in a large pediatric primary care network.
AB  - OBJECTIVE: To determine patterns of subspecialty utilization within a pediatric
      primary care network. DATA SOURCES/STUDY SETTING: Paid claims from a large not
      for-profit health plan for patients of The Pediatric Physicians' Organization at
      Children's, a network of private pediatric practices affiliated with Children's
      Hospital Boston. PRINCIPAL FINDINGS: The subspecialty visit rate was 1.01 visits
      per subject-year. In 2007, 56.8 percent of subjects had no subspecialty visits,
      whereas 4.2 percent had >= 5 visits; the corresponding figures in 2008 were 54.1
      and 4.5 percent, respectively. The most frequently visited subspecialties were
      Ophthalmology, Orthopedics, Dermatology, Otorhinolaryngology, and
      Allergy/Immunology. Visit rates varied sevenfold by practice. CONCLUSIONS: Wide
      practice variability in pediatric subspecialty utilization suggests an
      opportunity for reducing unnecessary visits. Better integration between primary
      care and the most commonly used subspecialties will be needed to meaningfully
      reduce unnecessary visits and enhance value.

PMID- 22375887
TI  - Identification of novel beta3-adrenoceptor agonists using energetic analysis,
      structure based pharmacophores and virtual screening.
AB  - beta3 Adrenergic receptor (beta3-AR), is a potential therapeutic target for the
      treatment of type II diabetes and obesity. We report the identification of novel
      compounds as beta3-AR agonists by integrating different approaches of energetic
      analysis, structure based pharmacophore designing and virtual screening. In a
      step wise filtering protocol, structure based virtual screening of 2, 33, 450
      compounds was done. These molecules were docked into the active site of the
      receptor utilizing three levels of accuracy; ligands passing the HTVS (high
      throughput virtual screening) step were subsequently analyzed in Glide SP
      (Standard Precision) and finally in Glide XP (Extra Precision) to estimate the
      receptor ligand binding affinities. In the second step a total of 300
      pharmacophore hypotheses were generated from a set of known and diverse beta3-AR
      agonists. The best hypothesis showed six features: three hydrogen bond acceptors,
      one positively charged group, and two aromatic rings. To cross validate,
      pharmacophore filtering was done on the set of shortlisted compounds from
      structure based VS (virtual screening). The different screening techniques
      employed were validated using enrichment factor calculations. The energetic based
      Pharmacophore performed fairly well at distinguishing active from the inactive
      compounds and yielded a greater diversity of active molecules whereas the number
      of actives retrieved in the case of structure based screening was the highest.

PMID- 22375888
TI  - A Swedish consensus on the surgical treatment of concomitant atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open
      heart surgery and is associated with increased morbidity and mortality. According
      to international guidelines, symptomatic and selected asymptomatic patients
      should be offered concomitant surgical AF ablation in conjunction with valvular
      or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut
      and-sew") procedure, with surgical incisions in both atria according to a
      specified pattern, in order to prevent AF reentry circuits from developing. Over
      90% of patients treated with the Cox Maze III procedure are free of AF after 1
      year. Recent developments in ablation technology have introduced several energy
      sources capable of creating nonconducting atrial wall lesions. In addition,
      simplified lesion patterns have been suggested, but results with these techniques
      have been unsatisfactory. There is a clear need for standardization in AF
      surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all
      Swedish units for cardiothoracic surgery, has therefore reached a consensus on
      surgical treatment of concomitant AF. This consensus emphasizes adherence to the
      lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in
      nonparoxysmal AF.

PMID- 22375889
TI  - Coagulopathy and hemostatic monitoring in cardiac surgery: an update.
AB  - OBJECTIVES: Cardiac surgery with cardiopulmonary bypass (CPB) causes severe
      derangements in the hemostatic system, which in turn puts the patient at risks of
      microvascular bleeding. Excessive transfusion and surgical re-exploration after
      cardiac surgery are potentially associated with a number of adverse outcomes
      including increased mortality. DESIGN: This review describes coagulopathies
      occurring in cardiac surgery and the monitoring of these. Viscoelastic hemostatic
      assays (VHA) have routinely been used in cardiac surgery for more than 25 years
      and at least 16 studies (involving more than 3250 patients, including three
      randomized controlled trials) have compared VHA to routine coagulation tests
      (RCoT) with regards to their ability to predict bleeding and re-do surgery and
      also with regards to transfusion requirements secondary to hemostatic therapy
      based on VHA vs. RCoT. RESULTS: All 16 studies demonstrated superiority with VHA
      as compared to RCoT both in predicting bleeding and need for re-do surgery and in
      reducing the total amount of blood transfusions by employing goal-directed
      administration of blood products based on VHA as compared RCoT based therapy or
      at the clinicians discretion. CONCLUSIONS: The different types of coagulopathies
      observed in patients undergoing cardiac surgery requires adequate and timely
      hemostatic therapy and real-time monitoring with WHA such as TEG/ROTEM and whole
      blood platelet aggregometry.

PMID- 22375890
TI  - Effect of substituting saturated with monounsaturated fatty acids on serum
      visfatin levels and insulin resistance in overweight women: a randomized cross
      over clinical trial.
AB  - OBJECTIVE: This study aimed to determine the effects of a monounsaturated fatty
      acids (MUFA)-rich diet on serum visfatin, interleukin-6 and insulin levels among
      overweight women. DESIGN: In this randomized cross-over clinical trial, 17
      premenopausal overweight women were included. Participants were randomly assigned
      to consume either a hypocaloric, saturated fatty acids (SFA)-rich diet (16% SFA
      and 8% MUFA) or a hypocaloric, MUFA-rich diet (16% MUFA and 8% SFA) for 12 weeks
      crossing over after a 2-week washout period. Percentages of energy from other
      macronutrients were similar between the two diets. Biochemical and anthropometric
      assessments were done at the first and at the end of each period. Statistical
      analyses were done using paired t-test. In all statistical analysis, p < 0.05 was
      considered as significant. RESULTS: The participant's mean body mass index was
      27.6 kg/m2. Mean percentages of MUFA intake were 13% during MUFA-rich diet and 7%
      during SFA-rich diet. The corresponding values for SFA intake were 8.5% and 14%,
      respectively. We failed to find any significant differences between two
      intervention diets in terms of their effect on the serum levels of IL-6, visfatin
      and insulin. However, serum visfatin and IL-6 levels increased during the SFA
      rich diet (0.4 +/- 0.4 ng/ml and 0.19 +/- 0.3 pg/ml, respectively) and decreased
      during the MUFA-rich diet (-0.7 +/- 0.5 ng/ml and -0.17 +/- 0.3 pg/ml,
      respectively). In spite of a slight reduction in both periods, changes in serum
      insulin levels did not reach significant levels comparing the two periods.
      CONCLUSIONS: Our findings did not support any significant effect of a MUFA-rich
      intake on serum IL-6 and insulin levels as compared with a SFA-rich diet;
      however, it has the potential to favourably affect serum visfatin levels.

PMID- 22375891
TI  - Impact of community-based interventions on condom use in the Tlicho region of
      Northwest Territories, Canada.
AB  - BACKGROUND: Since 2005, the Tlicho Community Services Agency (TCSA) in Canada's
      Northwest Territories (NT) has addressed rising rates of sexually transmitted
      infections (STI). In 2009, STI rates in the NT were ten times higher than the
      national rate and Tlicho regional rates were nearly four times that of the NT--91
      cases per 1000 people. We describe a social audit process that assessed the
      impact of an evidence-based community-led intervention. METHODS: A baseline
      survey of sexual health knowledge, attitudes and behaviours in 2006/07 provided
      evidence for a Community Action Research Team (CART) to develop and to put in
      place culturally appropriate interventions in the Tlicho region. A follow-up
      study in 2010 sought to assess the impact of CART activities on condom use and
      underlying conscious knowledge, attitudes, subjective norms, intention to change,
      sense of agency and discussions related to condom use and STI risks. We report
      the contrasts using Odds Ratios (OR) and 95% confidence intervals (CI). RESULTS:
      One in every three follow-up respondents (315/808) participated in at least one
      CART activity. Participation in highly ranked interventions was associated with
      increased condom use during the last sexual encounter (OR 1.45, 95%CI 1.07-1.98).
      Those exposed to three or more activities were more likely to talk openly about
      condoms (OR 2.08, 95%CI 1.41-3.28), but were also less likely to be monogamous
      (OR 0.49, 95%CI 0.29-0.90). CONCLUSIONS: The measurable impact on condom use
      indicates a strong beginning for the Tlicho community intervention programmes.
      The interventions also seem to generate increased discussion, often a precursor
      to action. The Tlicho can use the evidence to improve and refocus their
      programming, increase knowledge and continue to improve safe condom use
      practices.

PMID- 22375892
TI  - Evidence for a role of endogenous nesfatin-1 in the control of water drinking.
AB  - Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is
      produced in several brain areas known to be important in neuroendocrine,
      autonomic and metabolic function, including the hypothalamus and medulla. The
      hallmark action of the peptide is its ability at picomole doses to inhibit food
      and water intake in rodents and, indeed, the effect on water intake is more
      pronounced than that on food intake. In preliminary studies, we observed a
      decrease in hypothalamic NucB2 expression in response to overnight water
      deprivation even when food was present, which reversed when water was returned to
      the animals. We therefore hypothesised that the effect of nesfatin-1 on water
      drinking was independent of its anorexigenic action. Indeed, rats administered
      nesfatin-1 i.c.v. consumed significantly less water than controls in response to
      a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles
      after 18 h of fluid restriction (food present), or in response to a hypertonic
      challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1
      significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic
      paraventricular nucleus and resulted in exaggerated drinking responses to
      angiotensin II. The results obtained in the present study suggest that locally
      produced nesfatin-1 may be an important component of the hypothalamic mechanisms
      controlling fluid and electrolyte homeostasis.

PMID- 22375893
TI  - Determination of the structural features of a long-lived electron-transfer state
      of 9-mesityl-10-methylacridinium ion.
AB  - Extensive efforts have been devoted to developing electron donor-acceptor systems
      that mimic the utilization of solar energy that occurs in photosynthesis. X-ray
      crystallographic analysis shows how absorbed photon energy is stabilized in those
      compounds by structural changes upon photoinduced electron transfer (ET). In this
      study, structural changes of a simple electron donor-acceptor dyad, 9-mesityl-10
      methylacridinium cation (Acr(+)-Mes), upon photoinduced ET were directly observed
      by laser pump and X-ray probe crystallographic analysis. The N-methyl group in
      Acr(+) was bent, and a weak electrostatic interaction between Mes and a
      counteranion in the crystal (ClO(4)) was generated by photoinduced ET. These
      structural changes correspond to reduction and oxidation due to photoinduced ET
      and directly elucidate the mechanism in Acr(+)-Mes for mimicking photosynthesis
      efficiently.

PMID- 22375894
TI  - Diversity and recombination in Wolbachia and Cardinium from Bryobia spider mites.
AB  - BACKGROUND: Wolbachia and Cardinium are endosymbiotic bacteria infecting many
      arthropods and manipulating host reproduction. Although these bacteria are
      maternally transmitted, incongruencies between phylogenies of host and parasite
      suggest an additional role for occasional horizontal transmission. Consistent
      with this view is the strong evidence for recombination in Wolbachia, although it
      is less clear to what extent recombination drives diversification within single
      host species and genera. Furthermore, little is known concerning the population
      structures of other insect endosymbionts which co-infect with Wolbachia, such as
      Cardinium. Here, we explore Wolbachia and Cardinium strain diversity within nine
      spider mite species (Tetranychidae) from 38 populations, and quantify the
      contribution of recombination compared to point mutation in generating Wolbachia
      diversity. RESULTS: We found a high level of genetic diversity for Wolbachia,
      with 36 unique strains detected (64 investigated mite individuals). Sequence data
      from four Wolbachia genes suggest that new alleles are 7.5 to 11 times more
      likely to be generated by recombination than point mutation. Consistent with
      previous reports on more diverse host samples, our data did not reveal evidence
      for co-evolution of Wolbachia with its host. Cardinium was less frequently found
      in the mites, but also showed a high level of diversity, with eight unique
      strains detected in 15 individuals on the basis of only two genes. A lack of
      congruence among host and Cardinium phylogenies was observed. CONCLUSIONS: We
      found a high rate of recombination for Wolbachia strains obtained from host
      species of the spider mite family Tetranychidae, comparable to rates found for
      horizontally transmitted bacteria. This suggests frequent horizontal transmission
      of Wolbachia and/or frequent horizontal transfer of single genes. Our findings
      strengthens earlier reports of recombination for Wolbachia, and shows that high
      recombination rates are also present on strains from a restrictive host range.
      Cardinium was found co-infecting several spider mite species, and phylogenetic
      comparisons suggest also horizontal transmission of Cardinium among hosts.

PMID- 22375895
TI  - Evaluation of Lay Support in Pregnant women with Social risk (ELSIPS): a
      randomised controlled trial.
AB  - BACKGROUND: Maternal, neonatal and child health outcomes are worse in families
      from black and ethnic minority groups and disadvantaged backgrounds. There is
      little evidence on whether lay support improves maternal and infant outcomes
      among women with complex social needs within a disadvantaged multi-ethnic
      population in the United Kingdom (UK). METHOD/DESIGN: The aim of this study is to
      evaluate a lay Pregnancy Outreach Worker (POW) service for nulliparous women
      identified as having social risk within a maternity service that is
      systematically assessing social risks alongside the usual obstetric and medical
      risks. The study design is a randomised controlled trial (RCT) in nulliparous
      women assessed as having social risk comparing standard maternity care with the
      addition of referral to the POW support service. The POWs work alongside
      community midwifery teams and offer individualised support to women to encourage
      engagement with services (health and social care) from randomisation (before 28
      weeks gestation) until 6 weeks after birth. The primary outcomes have been chosen
      on the basis that they are linked to maternal and infant health. The two primary
      outcomes are engagement with antenatal care, assessed by the number of antenatal
      visits; and maternal depression, assessed using the Edinburgh Postnatal
      Depression Scale at 8-12 weeks after birth. Secondary outcomes include maternal
      and neonatal morbidity and mortality, routine child health assessments, including
      immunisation uptake and breastfeeding at 6 weeks. Other psychological outcomes
      (self efficacy) and mother-to-infant bonding will also be collected using
      validated tools.A sample size of 1316 will provide 90% power (at the 5%
      significance level) to detect increased engagement with antenatal services of 1.5
      visits and a reduction of 1.5 in the average EPDS score for women with two or
      more social risk factors, with power in excess of this for women with any social
      risk factor. Analysis will be by intention to treat. Qualitative research will
      explore the POWs' daily work in context. This will complement the findings of the
      RCT through a triangulation of quantitative and qualitative data on the process
      of the intervention, and identify other contextual factors that affect the
      implementation of the intervention. DISCUSSION: The trial will provide high
      quality evidence as to whether or not lay support (POW) offered to women
      identified with social risk factors improves engagement with maternity services
      and reduces numbers of women with depression. MREC NUMBER: 10/H1207/23 TRIAL
      REGISTRATION NUMBER: ISRCTN: ISRCTN35027323.

PMID- 22375896
TI  - Enantioselective and solvent-controlled diastereoselective Mannich reaction of
      isatin imines with hydroxyacetone: synthesis of 3-substituted 3-aminooxindoles.
AB  - The diastereoselectively switchable enantioselective Mannich reaction of isatin
      imines with hydroxyacetone is reported. The chiral primary amino acid catalyzed
      this Mannich reaction to afford both anti- and syn-Mannich adducts in high
      yields, good diastereoselectivities, and enantioselectivities. The reason for the
      solvent control of the diastereoselectivity phenomenon was investigated.

PMID- 22375897
TI  - Memory processes in learning disability subtypes of children born preterm.
AB  - The purpose of this study was to evaluate immediate auditory and visual memory
      processes in learning disability subtypes of 40 children born preterm. Three
      subgroups of children were examined: (a) primary language disability group (n =
      13), (b) perceptual-motor disability group (n = 14), and (c) no learning
      disability diagnosis group without identified language or perceptual-motor
      learning disability (n = 13). Between-group comparisons indicate no significant
      differences in immediate auditory or visual memory performances between language
      and perceptual-motor learning disability groups. Within-group comparisons
      revealed that both learning disability groups performed significantly lower on a
      task of immediate memory when the mode of stimulus presentation and mode of
      response were visual.

PMID- 22375898
TI  - Outcome after discontinuation of infliximab in patients with inflammatory bowel
      disease in clinical remission: an observational Danish single center study.
AB  - OBJECTIVE: To investigate duration of remission, including risk factors for
      relapse and response to retreatment with infliximab (IFX), in patients with
      Crohn's disease (CD) and ulcerative colitis (UC) who had discontinued IFX while
      in clinical remission. METHODS: Observational, single-center, retrospective study
      of all patients with a primary response to IFX who discontinued IFX therapy while
      in steroid-free remission. Relapse was defined as reintroduction of treatment
      with a biologic, systemic steroid or surgery. RESULTS: Of 219, 53 (24%) CD
      patients, and 28 of 97 (30%) UC patients discontinued IFX while in clinical
      steroid-free remission. The proportion of patients in remission declined steadily
      with 61% of CD patients, and 75% of UC patients being in remission after 1 year.
      Half the patients maintained remission after median 2 years (680 days (412-948))
      and 3.5 years (1334 days (995-1673)), respectively; p = 0.057. Twelve percent
      with CD and 40% with UC were in remission at the end of follow-up after 10 and
      4.5 years, respectively. Longer disease duration was associated with relapse in
      univariate analysis in CD, OR 1.1 (1.0-1.1), p = 0.022. Of 25, 24 CD patients
      (96%), and 5 of 7 UC patients (71%) experienced complete clinical remission when
      retreated with IFX after relapse. CONCLUSION: While the short-term prognosis
      seems favorable, the majority of patients who discontinue IFX while in remission
      relapse over time. The response to retreatment with IFX at relapse seems
      favorable in this subpopulation.

PMID- 22375899
TI  - Stimulus-responsive controlled release system by covalent immobilization of an
      enzyme into mesoporous silica nanoparticles.
AB  - Mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug
      delivery carriers for therapeutic agents. Herein, we explored the covalent
      immobilization of proteins into MSN to generate a stimulus-responsive controlled
      release system. First, MSN were functionalized with thiol groups using
      (mercaptopropyl)-trimethoxysilane (MPTMS). Functionalization was verified by X
      ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR)
      spectroscopy, and dynamic light scattering. The model enzyme carbonic anhydrase
      (CA) was coupled to sulfosuccinimidyl 6-[3'(2-pyridyldithio)
      propionamido]hexanoate (Sulfo-LC-SPDP) at a low ratio of 1:1 to prevent enzyme
      inactivation and subsequently covalently immobilized into MSN via thiol-disulfide
      interchange. The enzyme could be released from MSN with 10 mM glutathione, which
      represents intracellular redox conditions, while it remained bound to the MSN at
      extracellular redox conditions represented by 1 MUM glutathione. The activity of
      the released enzyme was >80% demonstrating that the enzyme was still largely
      functional and active after immobilization and release. Human cervical cancer
      (HeLa) cells were incubated with the MSN-CA bioconjugates at various
      concentrations for 24 h and the data show good biocompatibility. In summary, we
      demonstrate the potential of MSN as drug delivery systems for proteins.

PMID- 22375900
TI  - HIV risk behaviours among injecting drug users in Northeast India following scale
      up of a targeted HIV prevention programme.
AB  - BACKGROUND: In the Northeast Indian states of Manipur and Nagaland there has been
      an ongoing HIV epidemic among injecting drug users (IDUs) since the mid-1990s.
      Project ORCHID is an Avahan-funded HIV prevention project that has been working
      in selected districts of Manipur and Nagaland since 2004. It supports local
      partner non-government organisations (NGOs) to deliver a range of harm reduction
      interventions, and currently reaches approximately 14,500 IDUs across the two
      states. To assess changes in HIV risk behaviours two Behavioural Tracking Surveys
      (BTS) were undertaken among IDUs in 2007 and 2009. METHODS: The BTS used
      respondent driven sampling (RDS) to recruit adult male IDUs (18 years of age and
      above) from Ukhrul and Chandel districts in Manipur, and Kiphire and Zunheboto
      districts in Nagaland. This paper reports on analysis of socio-demographics, drug
      use and injecting practices, sexual behaviour and condom use, knowledge of HIV,
      and exposure to interventions. Descriptive data were analysed using RDSAT, and
      odds ratios were calculated in SPSS. RESULTS: The proportion of IDUs reporting
      NOT sharing needles / syringes at last injection increased substantially in
      Ukhrul (59.6% to 91.2%) and Zunheboto (45.5% to 73.8%), remained high in Chandel
      (97.0% to 98.9%), and remained largely unchanged in Kiphire (63.3% to 68.8%). The
      use of condoms with regular partners was low in all districts at both time
      points. In Ukhrul, Kiphire and Zunheboto the proportion of IDUs using condoms
      during sexual intercourse with a casual partner increased substantially to
      approximately 70-85%, whilst in Chandel the increase was only marginal (57.4% to
      63.6%). Exposure to NGO HIV prevention interventions was significantly associated
      (p<0.05) with lower odds of sharing needles during the previous month (Nagaland,
      OR=0.63; Manipur, OR 0.35). CONCLUSION: Despite district-level differences, the
      results from this BTS study indicate that exposure to HIV prevention services,
      predominately delivered in this region by NGOs, is associated with a reduced
      likelihood of engaging in HIV risk behaviours. IDUs using HIV prevention services
      are more likely to engage in safe injecting and sexual practices, and effort is
      required to sustain / increase opportunities for IDUs to access these services.
      These outcomes are a noteworthy achievement in a very challenging context.

PMID- 22375901
TI  - Methanotrophic communities in Australian woodland soils of varying salinity.
AB  - Despite their large areas and potential importance as methane sinks, the role of
      methane-oxidizing bacteria (MOB) in native woodland soils is poorly understood.
      These environments are increasingly being altered by anthropogenic disturbances,
      which potentially alter ecosystem service provision. Dryland salinity is one such
      disturbance and is becoming increasingly prevalent in Australian soils. We used
      microarrays and analysis of soil physicochemical variables to investigate the
      methane-oxidizing communities of several Australian natural woodland soils
      affected to varying degrees by dryland salinity. Soils varied in terms of
      salinity, gravitational water content, NO(3)-N, SO(4)-S and Mg, all of which
      explained to a significant degree MOB community composition. Analysis of the
      relative abundance and diversity of the MOB communities also revealed significant
      differences between soils of different salinities. Type II and type Ib
      methanotrophs dominated the soils and differences in methanotroph communities
      existed between salinity groups. The low salinity soils possessed less diverse
      MOB communities, including most conspicuously, the low numbers or absence of type
      II Methylocystis phylotypes. The differences in MOB communities suggest niche
      separation of MOB across varying salinities, as has been observed in the closely
      related ammonia-oxidizing bacteria, and that anthropogenic disturbance, such as
      dryland salinity, has the potential to alter MOB community and therefore the
      methane uptake rates in soils in which disturbance occurs.

PMID- 22375903
TI  - Enhanced apoptosis and senescence of bone-marrow-derived mesenchymal stem cells
      in patients with systemic lupus erythematosus.
AB  - Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from
      patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of
      proliferation, differentiation, secretion of cytokines, and immune modulation. In
      this study, we aimed to investigate whether apoptosis and senescence of SLE BMSCs
      were dysregulated. We found that there were increased frequencies of apoptotic
      and aging SLE BMSCs in comparison with those of normal controls. Notably, levels
      of Bcl-2 expression in SLE BMSCs were markedly decreased both at mRNA and protein
      levels. When BMSCs were induced to apoptosis by tumor necrosis factor-alpha (TNF
      alpha) stimulation in vitro, the Bax and caspase 8 expression in SLE BMSCs was
      significantly increased at mRNA levels. The activity of caspase 8 was also
      enhanced in SLE BMSCs. More cytochrome-C-positive pellets in the cytosolic
      fraction of BMSCs were detected in SLE patients than in normal controls. The
      expression of Fas and tumor necrosis factor-alpha receptor 1 in SLE BMSCs was
      significantly upregulated compared with normal controls, and the serum levels of
      FasL and TNF-alpha were also elevated. Moreover, intracellular reactive oxygen
      species levels of SLE BMSCs were higher than those of normal controls, with the
      activation of PI3K/AKT/FoxO3 signaling pathway. Taken together, our results
      demonstrate increased apoptosis and senescence in SLE BMSCs, which may be
      associated with the pathogenesis of SLE.

PMID- 22375905
TI  - Formation of iron(III) meso-chloro-isoporphyrin as a reactive chlorinating agent
      from oxoiron(IV) porphyrin pi-cation radical.
AB  - Iron(III) isoporphyrin, a tautomer of porphyrin with a saturated meso carbon, is
      one of the isoelectronic forms of oxoiron(IV) porphyrin pi-cation radical, which
      is known as an important reactive intermediate of various heme enzymes. The
      isoporphyrin has been believed to be incapable of catalyzing oxygenation and
      oxidation reactions. Here, we report that an oxoiron(IV) porphyrin pi-cation
      radical can be converted to iron(III) meso-chloro-isoporphyrin in the presence of
      trifluoroacetic acid and chloride ion. More importantly, this study shows the
      first evidence that iron(III) meso-chloro-isoporphyrin is an excellent reactive
      agent for chlorinating aromatic compounds and olefins. The results of this study
      suggest that the mechanism involves electrophilic chlorination of substrate with
      iron(III) meso-chloro-isoporphyrin.

PMID- 22375904
TI  - Antisocial behavioral syndromes and 3-year quality-of-life outcomes in United
      States adults.
AB  - OBJECTIVE: To examine 3-year quality-of-life (QOL) outcomes among United States
      adults with Diagnostic and Statistical Manual of Mental Disorders - Fourth
      Edition (DSM-IV) antisocial personality disorder (ASPD), syndromal adult
      antisocial behavior without conduct disorder (CD) before age 15 [adulthood
      antisocial behavioral syndrome (AABS), not a DSM-IV diagnosis], or no antisocial
      behavioral syndrome at baseline. METHOD: Face-to-face interviews (n = 34 653).
      Psychiatric disorders were assessed using the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule - DSM-IV Version. Health-related QOL was assessed
      using the Short-Form 12-Item Health Survey, version 2 (SF-12v2). Other outcomes
      included past-year Perceived Stress Scale-4 (PSS-4) scores, employment, receipt
      of Supplemental Security Income (SSI), welfare, and food stamps, and
      participation in social relationships. RESULTS: Antisocial personality disorder
      and AABS predicted poorer employment, financial dependency, social relationship,
      and physical health outcomes. Relationships of antisociality to SSI and food
      stamp receipt and physical health scales were modified by baseline age. Both
      antisocial syndromes predicted higher PSS-4, AABS predicted lower SF-12v2
      Vitality, and ASPD predicted lower SF-12v2 Social Functioning scores in women.
      CONCLUSION: Similar prediction of QOL by ASPD and AABS suggests limited utility
      of requiring CD before age 15 to diagnose ASPD. Findings underscore the need to
      improve prevention and treatment of antisocial syndromes.

PMID- 22375906
TI  - Recall of early non-fatal suicidality in a nationally representative sample of
      South Africans.
AB  - OBJECTIVES: Little is known about socio-demographic patterns of non-fatal
      suicidality in early life in South Africa. We investigated the prevalence of self
      reported early suicidality (suicidal ideation, planning and attempts) in a
      nationally representative sample of South Africans. DESIGN: As part of a larger
      mental health survey, 3158 individuals aged over 25 years were asked to recall
      whether they engaged in non-fatal suicidal behaviour in early life (measured from
      childhood to 25 years). Race-based discrimination institutionalised under
      Apartheid profoundly influenced delivery and outcomes in health and other social
      services. Racial categories entrenched during Apartheid were therefore used to
      analyse data collected from individuals born before 1946, 1947-1956, 1957-1966
      and 1967-1976. RESULTS: 3.4% (95% CI=2.6-4.1) of participants recalled early
      suicidal behaviour. The youngest group (born 1967-1976) recalled higher rates of
      early suicidality than older groups in all races. In unadjusted analysis, white
      people were 2.84 (95% CI=1.62-4.97) and coloured people 1.84 (95% CI=1.15-2.93)
      times more likely than black people to recall early suicidality. Individuals
      growing up in urban and higher socio-economic settings were approximately twice
      (OR=2.2; 95% CI=1.14-4.28 and OR=1.92; 95% CI=1.27-2.90) as likely to recall
      early suicidality as those growing up in rural and lower socio-economic settings.
      Those with post-primary education were 2.79 (CI=1.71-4.53) times as likely to
      recall early suicidality as those with no or only primary education. Racial
      differences ceased to be significant after adjustment for rural/urban location
      and other socio-economic measures estimated for early life. CONCLUSION: The study
      provides novel evidence of increasing levels of early non-fatal suicidality
      recalled by younger South Africans. Levels appeared significantly higher in
      Whites than in Blacks. Socio-economic contexts in early life were interpreted as
      mediators rather than confounders of the association between race and recalled
      early suicidality. The findings for decreased levels of suicidality among
      participants growing up in lower socio-economic strata and rural settings in
      South Africa require further investigation. The need for widespread suicide
      prevention programmes targeting young people at a population level is emphasised.

PMID- 22375909
TI  - Some general considerations about the clinicopathologic aspects of soft tissue
      tumors in children and adolescents.
AB  - Soft tissue tumors in children and adolescents are an important group of
      neoplasms, pseudoneoplasms, and tumefactive malformations with some distinctive
      clinicopathologic, genetic, syndromic, and therapeutic implications. In addition
      to the basic pathologic examination, there is the availability of diagnostic
      adjuncts in various settings based upon the histopathologic features that
      facilitate and/or corroborate a diagnosis. Immunohistochemistry, cytogenetics,
      molecular genetics, and an ever-increasing array of new technologies are
      available to address specific diagnostic questions and even potential therapeutic
      strategies. This review focuses upon some of the unique aspects of soft tissue
      tumors in children, including the classification, approach to the diagnosis,
      grading, clinical and pathologic staging, therapy-related changes, pathogenesis,
      and risk factors.

PMID- 22375908
TI  - Development of a nurse home visitation intervention for intimate partner
      violence.
AB  - BACKGROUND: Despite an increase in knowledge about the epidemiology of intimate
      partner violence (IPV), much less is known about interventions to reduce IPV and
      its associated impairment. One program that holds promise in preventing IPV and
      improving outcomes for women exposed to violence is the Nurse-Family Partnership
      (NFP), an evidence-based nurse home visitation program for socially disadvantaged
      first-time mothers. The present study developed an intervention model and
      modification process to address IPV within the context of the NFP. This included
      determining the extent to which the NFP curriculum addressed the needs of women
      at risk for IPV or its recurrence, along with client, nurse and broader
      stakeholder perspectives on how best to help NFP clients cope with abusive
      relationships. METHODS: Following a preliminary needs assessment, an exploratory
      multiple case study was conducted to identify the core components of the proposed
      IPV intervention. This included qualitative interviews with purposeful samples of
      NFP clients and community stakeholders, and focus groups with nurse home visitors
      recruited from four NFP sites. Conventional content analysis and constant
      comparison guided data coding and synthesis. A process for developing complex
      interventions was then implemented. RESULTS: Based on data from 69 respondents,
      an IPV intervention was developed that focused on identifying and responding to
      IPV; assessing a client's level of safety risk associated with IPV; understanding
      the process of leaving and resolving an abusive relationship and system
      navigation. A need was identified for the intervention to include both universal
      elements of healthy relationships and those tailored to a woman's specific level
      of readiness to promote change within her life. A clinical pathway guides nurses
      through the intervention, with a set of facilitators and corresponding
      instructions for each component. CONCLUSIONS: NFP clients, nurses and
      stakeholders identified the need for modifications to the existing NFP program;
      this led to the development of an intervention that includes universal and
      targeted components to assist NFP nurses in addressing IPV with their clients.
      Plans for feasibility testing and evaluation of the effectiveness of the IPV
      intervention embedded within the NFP, and compared to NFP-only, are discussed.

PMID- 22375910
TI  - Rho kinase (ROK)-related proteins in human cavernous arteries: an
      immunohistochemical and functional approach.
AB  - INTRODUCTION: Rho kinases (ROKs) cause calcium-independent modulation of smooth
      muscle contraction. A significant role for the RhoA/ROK pathway in mediating the
      contraction of the penile erectile tissue has been suggested. Moreover, it has
      been postulated that ROK activity might represent a key factor in the
      pathophysiology of erectile dysfunction. Up until today, little is known on the
      significance of ROK and related proteins in the control of blood flow in the
      corpus cavernosum. AIM: To investigate by means of immunohistochemistry and organ
      bath studies the significance of the Rho pathway in human cavernous arteries.
      MAIN OUTCOME MEASURES: The expression of ROK1, ROK2, RhoA, and RhoGDI in human
      cavernous arteries was investigated by means of immunohistochemistry; myographic
      studies were conducted in order to characterize the effects of the ROK inhibitor
      Y27632 on isolated cavernous arteries. METHODS: Specimens of human cavernous
      arteries were processed for immunohistochemistry for ROK1, ROK2, RhoA, and
      RhoGDI. Circular penile vascular segments were mounted in a tissue bath and the
      effects of increasing concentrations of the ROK inhibitor Y27632 on the tension
      induced by norepinephrine (NE, 1 uM) were investigated. RESULTS: Alpha-actin
      immunoreactive cavernous arterioles also presented abundant staining specific for
      ROK1, ROK2, RhoA, and RhoGDI in the smooth musculature of the vascular wall.
      Cumulative addition of Y27632 dose-dependently reversed the tension induced by NE
      of isolated arterial segments. Y27632 produced relaxant responses with a
      reversion of tension of 34.3 +/- 11.8% at a concentration of 1 uM. CONCLUSION:
      The findings are in support for a role of the Rho/ROK-mediated signaling in the
      regulation of muscle tone of human cavernous arteries.

PMID- 22375911
TI  - Polyporous metal-coordination frameworks.
AB  - Starting from a chiral building block--alpha-cyclodextrin--and rubidium salts,
      the crystallization of a complex of chiral helices, which constitute a "green"
      porous coordination polymer, has been realized. Cyclodextrin molecules
      coordinated by rubidium ions form porous, infinitely long left-handed helical
      channels, interdigitated with each other. A theoretical examination of the
      potential of this new material to act as a medium for chiral separation is
      presented.

PMID- 22375914
TI  - Synthesis of trisubstituted isoxazoles by palladium(II)-catalyzed cascade
      cyclization-alkenylation of 2-alkyn-1-one O-methyl oximes.
AB  - A palladium-catalyzed, cascade 5-endo-dig cyclization-alkenylation synthesis of
      isoxazoles has been developed. The addition of 1 equiv of n-Bu(4)NBr
      significantly increases the yield of the desired 4-alkenyl-3,4,5-trisubstituted
      isoxazoles. A variety of trisubstituted isoxazoles are prepared in moderate to
      excellent yields. One example of the synthesis of a naphthoisoxazole is reported
      by a cascade cyclization-alkenylation-Heck reaction.

PMID- 22375915
TI  - Intuitive geometry and visuospatial working memory in children showing symptoms
      of nonverbal learning disabilities.
AB  - Visuospatial working memory (VSWM) and intuitive geometry were examined in two
      groups aged 11-13, one with children displaying symptoms of nonverbal learning
      disability (NLD; n = 16), and the other, a control group without learning
      disabilities (n = 16). The two groups were matched for general verbal abilities,
      age, gender, and socioeconomic level. The children were presented with simple
      storage and complex-span tasks involving VSWM and with the intuitive geometry
      task devised by Dehaene, Izard, Pica, and Spelke (2006 ). Results revealed that
      the two groups differed in the intuitive geometry task. Differences were
      particularly evident in Euclidean geometry and in geometrical transformations.
      Moreover, the performance of NLD children was worse than controls to a larger
      extent in complex-span than in simple storage tasks, and VSWM differences were
      able to account for group differences in geometry. Finally, a discriminant
      function analysis confirmed the crucial role of complex-span tasks involving VSWM
      in distinguishing between the two groups. Results are discussed with reference to
      the relationship between VSWM and mathematics difficulties in nonverbal learning
      disabilities.

PMID- 22375912
TI  - Host gene response to endosymbiont and pathogen in the cereal weevil Sitophilus
      oryzae.
AB  - BACKGROUND: Insects thriving on nutritionally poor habitats have integrated
      mutualistic intracellular symbiotic bacteria (endosymbionts) in a bacteria
      bearing tissue (the bacteriome) that isolates the endosymbionts and protects them
      against a host systemic immune response. Whilst the metabolic and physiological
      features of long-term insect associations have been investigated in detail over
      the past decades, cellular and immune regulations that determine the host
      response to endosymbionts and pathogens have attracted interest more recently.
      RESULTS: To investigate bacteriome cellular specificities and weevil immune
      responses to bacteria, we have constructed and sequenced 7 cDNA libraries from
      Sitophilus oryzae whole larvae and bacteriomes. Bioinformatic analysis of 26,886
      ESTs led to the generation of 8,941 weevil unigenes. Based on in silico analysis
      and on the examination of genes involved in the cellular pathways of potential
      interest to intracellular symbiosis (i.e. cell growth and apoptosis, autophagy,
      immunity), we have selected and analyzed 29 genes using qRT-PCR, taking into
      consideration bacteriome specificity and symbiosis impact on the host response to
      pathogens. We show that the bacteriome tissue accumulates transcripts from genes
      involved in cellular development and survival, such as the apoptotic inhibitors
      iap2 and iap3, and endosomal fusion and trafficking, such as Rab7, Hrs, and
      SNARE. As regards our investigation into immunity, we first strengthen the
      bacteriome immunomodulation previously reported in S. zeamais. We show that the
      sarcotoxin, the c-type lysozyme, and the wpgrp2 genes are downregulated in the S.
      oryzae bacteriome, when compared to aposymbiotic insects and insects challenged
      with E. coli. Secondly, transcript level comparison between symbiotic and
      aposymbiotic larvae provides evidence that the immune systemic response to
      pathogens is decreased in symbiotic insects, as shown by the relatively high
      expression of wpgrp2, wpgrp3, coleoptericin-B, diptericin, and sarcotoxin genes
      in aposymbiotic insects. CONCLUSIONS: Library sequencing significantly increased
      the number of unigenes, allowing for improved functional and genetic
      investigations in the cereal weevil S. oryzae. Transcriptomic analyses support
      selective and local immune gene expression in the bacteriome tissue and uncover
      cellular pathways that are of potential interest to bacteriocyte survival and
      homeostasis. Bacterial challenge experiments have revealed that the systemic
      immune response would be less induced in a symbiotic insect, thus highlighting
      new perspectives on host immunity in long-term invertebrate co-evolutionary
      associations.

PMID- 22375916
TI  - Gold nanoparticles capped by a GC-containing peptide functionalized with an RGD
      motif for integrin targeting.
AB  - Gold nanoparticles were obtained by reduction of a tetrachloroaurate aqueous
      solution in the presence of a RGD-(GC)(2) peptide as stabilizer. As comparison,
      the behavior of the (GC)(2) peptide has been studied. The (GC)(2) and RGD-(GC)(2)
      peptides were prepared ad hoc by Fmoc synthesis. The colloidal systems have been
      characterized by UV-visible, TGA, ATR-FTIR, mono and bidimensional NMR
      techniques, confocal and transmission (TEM) microscopy, zeta-potential, and light
      scattering measurements. The efficient cellular uptake of Au-RGD-(GC)(2) and Au
      (GC)(2) stabilized gold nanoparticles into U87 cells (human glioblastoma cells)
      were investigated by confocal microscopy and compared with the behavior of
      (GC)(2) capped gold nanoparticles. A quantitative determination of the
      nanoparticles taken up has been carried out by measuring the pixel brightness of
      the images, a measure that highlighted the importance of the RGD termination of
      the peptide. Insight in the cellular uptake mechanism was investigated by TEM
      microscopy. Various important evidences indicated the selective uptake of RGD
      (GC)(2) gold nanoparticles into the nucleus.

PMID- 22375918
TI  - Bio-markers as tools for discovery of new psoriasis therapies.

PMID- 22375917
TI  - Vasopressin and oxytocin: keys to understanding the neural control of physiology
      and behaviour.

PMID- 22375919
TI  - Effect of a pathological scapular tilt after total shoulder arthroplasty.
AB  - Total shoulder arthroplasty (TSA) is an accepted and most successfully used
      treatment for different shoulder pathologies. Different risk factors for the
      failure of the prosthesis are known. A pathological scapular orientation,
      observed in elderly people or in patients suffering from neuromuscular diseases,
      could be a cause of failure, which has not been investigated yet. To test this
      hypothesis, a numerical musculoskeletal model of the glenohumeral joint was used
      to compare two TSA cases: a reference normal case and a case with a pathological
      anterior tilt of the scapula. An active abduction of 150 degrees  was simulated.
      Joint force, contact pattern, polyethylene and cement stress were evaluated for
      both cases. The pathological tilt slightly increased the joint force and the
      contact pressure, but also shifted the contact pattern. This eccentric contact
      increased the stress level within the polyethylene of the glenoid component and
      within the surrounding cement layer. This adverse effect occurred mainly during
      the first 60 degrees  of abduction. Therefore, a pathological orientation of the
      scapula may increase the risk of a failure of the cement layer around the glenoid
      component. These preliminary numerical results should be confirmed by a clinical
      study. 

PMID- 22375921
TI  - Migration of human mesenchymal stem cells under low shear stress mediated by
      mitogen-activated protein kinase signaling.
AB  - Human mesenchymal stem cells (hMSCs) are attractive candidates for cell-based
      tissue repair approaches and have been used as vectors for delivering therapeutic
      genes to sites of injury. It is believed that hMSCs are able to detect and
      respond to shear stress due to blood and interstitial fluid flow through
      mechanotransduction pathways after transplantation. However, information
      regarding hMSC migration under shear stress and its mechanism is still limited.
      In this study, we examined the effect of shear stress on hMSC migration and the
      role of mitogen-activated protein kinases (MAPKs) in their migration. Shear
      stress between 0.2 and 10 Pa, which was produced by the flow medium, was exerted
      on fluorescently labeled hMSCs. Cell migration was evaluated using the scratch
      wound assay, and images were captured using a microscope equipped with a digital
      3CCD camera. The results showed that hMSCs subjected to a shear stress of 0.2 Pa
      caused notably faster wound closure than statically cultured hMSCs, while
      migration in the 0.5- and 1-Pa shear stress group did not differ significantly
      from that in the control group. Shear stress >2 Pa markedly inhibited hMSC
      migration. hMSCs subjected to a shear stress of 0.2 Pa displayed an increase in
      extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases
      (JNK), and p38 MAPK activation for up to 60 min, while a shear stress of 2 Pa
      abrogated the activation. JNK and p38 MAPK inhibitors completely abolished the
      effect of shear stress on hMSC migration, while significant differences were
      observed between the ERK1/2 inhibitor-treated static control and shear stress
      groups. Taken together, these results demonstrate that low shear stress
      effectively induces hMSC migration and that JNK and p38 MAPK play more prominent
      roles in shear stress-induced migration than ERK1/2.

PMID- 22375920
TI  - Impact of bone harvesting techniques on cell viability and the release of growth
      factors of autografts.
AB  - BACKGROUND: Autogenous bone grafts obtained by different harvesting techniques
      behave differently during the process of graft consolidation; the underlying
      reasons are however not fully understood. One theory is that harvesting
      techniques have an impact on the number and activity of the transplanted cells
      which contribute to the process of graft consolidation. MATERIALS AND METHODS: To
      test this assumption, porcine bone grafts were harvested with four different
      surgical procedures: bone mill, piezosurgery, bone drilling (bone slurry), and
      bone scraper. After determining cell viability, the release of molecules
      affecting bone formation and resorption was assessed by reverse transcription
      polymerase chain reaction and immunoassay. The mitogenic and osteogenic activity
      of the conditioned media was evaluated in a bioassay with isolated bone cells.
      RESULTS: Cell viability and the release of molecules affecting bone formation
      were higher in samples harvested by bone mill and bone scraper when compared with
      samples prepared by bone drilling and piezosurgery. The harvesting procedure also
      affected gene expression, for example, bone mill and bone scraper samples
      revealed significantly higher expression of growth factors such as bone
      morphogenetic protein-2 and vascular endothelial growth factor compared with the
      two other modalities. Receptor activator of nuclear factor kappa B ligand
      expression was lowest in bone scraper samples. CONCLUSION: These data can provide
      a scientific basis to better understand the impact of harvesting techniques on
      the number and activity of transplanted cells, which might contribute to the
      therapeutic outcome of the augmentation procedure.

PMID- 22375922
TI  - The toxicology and immunology of detergent enzymes.
AB  - Detergent enzymes have a very good safety profile, with almost no capacity to
      generate adverse acute or chronic responses in humans. The exceptions are the
      limited ability of some proteases to produce irritating effects at high
      concentrations, and the intrinsic potential of these bacterial and fungal
      proteins to act as respiratory sensitizers, demonstrated in humans during the
      early phase of the industrial use of enzymes during the 1960s and 1970s. How
      enzymes generate these responses are beginning to become a little clearer, with a
      developing appreciation of the cell surface mechanism(s) by which the enzymatic
      activity promotes the T-helper (T(H))-2 cell responses, leading to the generation
      of IgE. It is a reasonable assumption that the majority of enzyme proteins
      possess this intrinsic hazard. However, toxicological methods for characterizing
      further the respiratory sensitization hazard of individual enzymes remains a
      problematic area, with the consequence that the information feeding into risk
      assessment/management, although sufficient, is limited. Most of this information
      was in the past generated in animal models and in vitro immunoassays that assess
      immunological cross-reactivity. Ultimately, by understanding more fully the
      mechanisms which drive the IgE response to enzymes, it will be possible to
      develop better methods for hazard characterization and consequently for risk
      assessment and management.

PMID- 22375923
TI  - Buffering and plasticity in vital rates of oldfield rodents.
AB  - 1. Under the hypothesis of environmental buffering, populations are expected to
      minimize the variance of the most influential vital rates; however, this may not
      be a universal principle. Species with a life span <1 year may be less likely to
      exhibit buffering because of temporal or seasonal variability in vital rate
      sensitivities. Further, plasticity in vital rates may be adaptive for species in
      a variable environment with reliable cues. 2. We tested for environmental
      buffering and plasticity in vital rates using stage-structured matrix models from
      long-term data sets in four species of grassland rodents. We used periodic
      matrices to estimate stochastic elasticity for each vital rate and then tested
      for correlations with a standardized coefficient of variation for each rate. 3.
      We calculated stochastic elasticities for individual months to test for an
      association between increased reproduction and the influence of reproduction,
      relative to survival, on the population growth rate. 4. All species showed some
      evidence of buffering. The elasticity of vital rates of Peromyscus leucopus
      (Rafinesque, 1818), Sigmodon hispidus Say & Ord, 1825 and Microtus ochrogaster
      (Wagner, 1842) was negatively related to vital rate CV. Elasticity and vital rate
      CV were negatively related in Peromyscus maniculatus (Wagner, 1845), but the
      relationship was not statistically significant. Peromyscus leucopus and M.
      ochrogaster showed plasticity in vital rates; reproduction was higher following
      months where elasticity for reproduction exceeded that of survival. 5. Our
      results suggest that buffering is common in species with fast life histories;
      however, some populations that exhibit buffering are capable of responding to
      short-term variability in environmental conditions through reproductive
      plasticity.

PMID- 22375925
TI  - Magnetic dipolar interactions in solid gold nanosphere dimers.
AB  - We report the first observation of a magnetic dipolar contribution to the
      nonlinear optical (NLO) response of colloidal metal nanostructures. Second-order
      NLO responses from several individual solid gold nanosphere (SGN) dimers, which
      we prepared by a bottom-up approach, were examined using polarization-resolved
      second harmonic generation (SHG) spectroscopy at the single-particle level.
      Unambiguous circular dichroism in the SH signal was observed for most of the
      dimeric colloids, indicating that the plasmon field located within the
      interparticle gap was chiral. Detailed analysis of the polarization line shapes
      of the SH intensities obtained by continuous polarization variation suggested
      that the effect resulted from strong magnetic-dipole contributions to the
      nanostructure's optical properties.

PMID- 22375924
TI  - The dyslexia candidate gene DYX1C1 is a potential marker of poor survival in
      breast cancer.
AB  - BACKGROUND: The dyslexia candidate gene, DYX1C1, shown to regulate and interact
      with estrogen receptors and involved in the regulation of neuronal migration, has
      recently been proposed as a putative cancer biomarker. This study was undertaken
      to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA
      and protein expression in breast cancer. METHODS: DYX1C1 mRNA expression was
      assessed at the mRNA level in three independent population-derived patient
      cohorts. An association to estrogen/progesterone receptor status, Elston grade,
      gene expression subtype and lymph node status was analyzed within these cohorts.
      DYX1C1 protein expression was examined using immunohistochemistry in cancer and
      normal breast tissue. The statistical analyses were performed using the non
      parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate
      proportional hazard (Cox) model. RESULTS: DYX1C1 mRNA is significantly more
      highly expressed in tumors that have been classified as estrogen receptor alpha
      and progesterone receptor-positive. The expression of DYX1C1 among the molecular
      subtypes shows the lowest median expression within the basal type tumors, which
      are considered to have the worst prognosis. The expression of DYX1C1 is
      significantly lower in tumors graded as Elston grade 3 compared with grades 1 and
      2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast
      tissues examined. Positive protein expression was significantly correlated to
      overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to
      any of the variables linked with mRNA expression. CONCLUSION: We show that the
      expression of DYX1C1 in breast cancer is associated with several
      clinicopathological parameters and that loss of DYX1C1 correlates with a more
      aggressive disease, in turn indicating that DYX1C1 is a potential prognostic
      biomarker in breast cancer.

PMID- 22375926
TI  - The relation between serum lipids and lutein and zeaxanthin in the serum and
      retina: results from cross-sectional, case-control and case study designs.
AB  - BACKGROUND: The xanthophyll carotenoids lutein (L) and zeaxanthin (Z) are found
      in and around the macula of the primate retina, where they are termed macular
      pigment (MP). Dietary L and Z are absorbed with fat in the gut and transported on
      lipoproteins to the retina. Both MP and serum lipoproteins have been related to
      risk for neurodegenerative diseases such as age-related macular degeneration
      (AMD). L and Z are carried on both HDL (related to reduced risk of AMD) and LDL
      (related to increased risk). The purpose of this set of studies was to analyze
      the relation between L and Z in the serum and retina with the circulating lipid
      profile. METHODS: In all experiments, lipoproteins were measured enzymatically
      from plasma, and MP optical density (MPOD) was measured using customized
      heterochromatic flicker photometry. Experiment 1: Relations between serum L and
      Z, MPOD and lipoprotein levels. 108 young, healthy subjects (M = 23.2, SD = 4.12
      years) participated. Lipoprotein levels and MPOD were measured. In a subset of 66
      participants, serum L and Z levels were also measured using high-performance
      liquid chromatography. Experiment 2: Relations between lipoprotein levels and
      MPOD in statin users. 20 subjects (M = 58.05, SD = 11.08 years) taking statin
      medication and 20 subjects (M = 57.95, SD = 11.03 years) not taking satin were
      recruited for participation. MPOD and lipoprotein levels were measured.
      Experiment 3: lowering lipoprotein levels to impact MPOD. One individual (aged 41
      years) with high MP density adhered first to an atorvastatin regimen, then, after
      a wash-out period, to a rosuvastatin regimen. RESULTS: Experiment 1: HDL were
      significantly (p < 0.05) related to MPOD (r = 0.33), to serum L (r = 0.36) and to
      serum Z (r = 0.26). MPOD was also significantly related to total cholesterol (r =
      0.19). Experiment 2: MPOD was not lower in statin users when compared to matched
      non-statin users, but MPOD decreased significantly with increased duration of
      statin use (r = -0.63). Experiment 3: Administration of a statin regimen reduced
      MPOD with atorvastatin (p < 0.05) but not with rosuvastatin. CONCLUSIONS: Serum
      xanthophylls, retinal xanthophylls and lipoprotein concentrations are
      significantly related, and changing lipoprotein levels may impact levels of
      retinal xanthophylls.

PMID- 22375928
TI  - Expanded bodipy dyes: anion sensing using a bodipy analog with an additional
      difluoroboron bridge.
AB  - Oxalyl-tethered pyrroles can be doubly bridged with two difluoroboron chelating
      units to yield bright orange dyes. Interestingly, in polar organic solvents, the
      addition of fluoride and cyanide result in reversible detachment of the otherwise
      stable difluoroboron bridges, resulting in sharp changes in color. Thus, this
      novel compound behaves as a highly selective chromogenic sensor for fluoride and
      cyanide ions.

PMID- 22375927
TI  - Assessing cognitive changes in the elderly: reliable change indices for the Mini
      Mental State Examination.
AB  - OBJECTIVE: The diagnosis of dementia includes evidence of decline in cognitive
      functioning over time measured by objective cognitive tasks. Normative data for
      changes adjusted for the impact of socio-demographic factors on cognitive test
      performance are lacking to interpret changes in Mini-Mental State Examination
      (MMSE) test scores. METHOD: As part of the German Study on Ageing, Cognition and
      Dementia in Primary Care Patients (AgeCoDe Study), a sample of 1090 cognitively
      healthy individuals, aged 75 years and older, was assessed at 1.5-year intervals
      over a period of 4.5 years using the MMSE. Age- and education-specific Reliable
      Change Indices (RCIs) were computed. RESULTS: Age and education were
      significantly associated with MMSE test performance, and gender indicated no
      impact. Across different age and education subgroups, changes from at least 2 up
      to 3 points indicated significant (i.e., reliable) changes in MMSE test scores at
      the 90% confidence level. Furthermore, the calculation of RCIs for individual
      patients is demonstrated. CONCLUSION: This study provides age- and education
      specific MMSE norms based upon RCI methods to interpret cognitive changes in
      older age groups. The computation of RCI scores improves the interpretation of
      changes in MMSE test scores by controlling for measurement error, practice
      effects, or regression to the mean.

PMID- 22375929
TI  - Trajectories of depressive symptoms and fatigue among postpartum women.
AB  - OBJECTIVES: To identify and characterize the trajectories of depressive and
      fatigue symptoms and determine the relationship between these two trajectories
      and associated predictors. DESIGN: A prospective, follow-up study. SETTING: A
      teaching medical center in central Taiwan. PARTICIPANTS: A convenience sample of
      121 low-risk, childbearing women. METHODS: Depressive and fatigue symptoms were
      assessed using the Edinburgh Postnatal Depression Scale and Fatigue Continuum
      Form respectively during the third trimester (time 1), one day postpartum (time
      2), three days postpartum (time 3), and one week postpartum (time 4).
      Participants also completed structured questionnaires on demographic features,
      health status, and sleep quality. RESULTS: The mean age of participants was 31.2
      years. We observed four distinctive trajectories of depressive symptoms and three
      trajectories of fatigue using group-based trajectory modeling. A frequent
      conoccurrence of similar levels of these symptoms was found; that is, mothers in
      the high-risk depressive symptoms group were most likely to fall into the high
      risk group for fatigue. Joint trajectories were predicted by poor sleep score
      (odds ratio = 2.96, 95% confidence interval = 1.2, 7.3) using multinomial
      logistic regression analysis. CONCLUSION: Overlapping but distinct trajectories
      of depressive symptoms and fatigue were found. These results suggest that
      differentiation between depressive symptoms and fatigue is possible and important
      for improving care during the early postpartum period.

PMID- 22375930
TI  - Preparation and characterization of nimesulide containing nanocrystal
      formulations.
AB  - The aim of this study was to develop and characterize nanocrystal formulation
      containing nimesulide. Physical mixture of drug and excipient
      (nimesulide:pluronic F127, 1:0.5) was also prepared to compare the efficiency of
      formulations. The physicochemical characteristics of the formulations were
      determined by means of Fourier transform infrared spectroscopy (FT-IR),
      differential scanning calorimetry (DSC), and X-ray diffractometry. Particle size,
      saturation solubilities as a function of pH, and permeability across Caco-2
      monolayers were determined for nimesulide in powder, physical mixture, and
      nanocrystal formulations. In FT-IR analysis, the characteristic peaks that belong
      to nimesulide were seen in all formulations. X-ray diffractograms displayed that
      crystalline structure of nimesulide was conserved in the nanocrystal formulation.
      The interaction between nimesulide and pluronic F127 was demonstrated by DSC
      analysis. In all conditions, the average particle size of the nanocrystal
      formulations decreased significantly (p < 0.05) as compared with nimesulide and
      physical mixture. The solubility of nimesulide in nanocrystal formulation was
      higher than those of nimesulide in powder and physical mixture. Permeability
      studies revealed that nimesulide is a highly permeable compound whether in powder
      form or in physical mixture and nanocrystal formulation. All these results
      clearly demonstrate that aqueous solubility of poorly water-soluble compounds can
      be improved by preparing nanocrystal formulations.

PMID- 22375931
TI  - From tendon to nerve: an MSC for all seasons.
AB  - The potential of mesenchymal stem cells (MSCs) to regenerate damaged tissue is
      well documented, as this specialized progenitor cell type exhibits superior
      cellular properties, and would allow medical as well as ethical limitations to be
      overcome. By now, MSCs have been successfully introduced in manifold experimental
      approaches within the newly defined realm of Regenerative Medicine. Advanced
      methods for in vitro cell expansion, defined induction of distinct
      differentiation processes, 3-dimensional culture on specific scaffold material,
      and tissue engineering approaches have been designed, and many clinical trials
      not only have been launched, but recently could be completed. To date, most of
      the MSC-based therapeutic approaches have been executed to address bone,
      cartilage, or heart regeneration; further, prominent studies have shown the
      efficacy of ex vivo expanded and infused MSCs to countervail graft-versus-host
      disease. Yet more fields of application emerge in which MSCs unfold beneficial
      effects, and presently, therapies that effectively ameliorate nonhealing
      conditions after tendon or spinal cord injury are, courtesy of scientific
      research, forging ahead to the clinical trial stage.

PMID- 22375932
TI  - Light trapping in solar cells: can periodic beat random?
AB  - Theory predicts that periodic photonic nanostructures should outperform their
      random counterparts in trapping light in solar cells. However, the current
      certified world-record conversion efficiency for amorphous silicon thin-film
      solar cells, which strongly rely on light trapping, was achieved on the random
      pyramidal morphology of transparent zinc oxide electrodes. Based on insights from
      waveguide theory, we develop tailored periodic arrays of nanocavities on glass
      fabricated by nanosphere lithography, which enable a cell with a remarkable short
      circuit current density of 17.1 mA/cm(2) and a high initial efficiency of 10.9%.
      A direct comparison with a cell deposited on the random pyramidal morphology of
      state-of-the-art zinc oxide electrodes, replicated onto glass using nanoimprint
      lithography, demonstrates unambiguously that periodic structures rival random
      textures.

PMID- 22375933
TI  - Introduction: contextualising "rights" in sexual and reproductive health.

PMID- 22375934
TI  - Prevalence of low back pain and associated occupational factors among Chinese
      coal miners.
AB  - BACKGROUND: Very few studies have evaluated the association between occupational
      factors and low back pain (LBP) among miners. The epidemiological data on LBP in
      Chinese miners are limited. The aim of this study was to measure the prevalence
      of low back pain in Chinese coal miners and to investigate the role of
      occupational factors. METHODS: A cross-sectional survey was conducted to examine
      1573 coal miners in northern China. The prevalence of LBP over a 12-month period
      was assessed using the Nordic Musculoskeletal Questionnaire. Odds ratios were
      calculated to examine the association between the prevalence of LBP over a 12
      month period and occupational factors using logistic regression. RESULTS: Among
      the coal miners, 64.9% self-reported LBP in a 12-month period. Occupational
      factors associated with LBP were identified, including tasks with a high degree
      of repetitiveness (OR 1.3, 95%CI 1.0-1.6), tasks characterized by a high level of
      physical demand (OR 1.4, 95% CI 1.1-1.8), posture requiring extreme bending (OR
      1.6, 95% CI 1.2-1.7) and insufficient recovery time (OR 1.4, 95% CI 1.0-1.8).
      CONCLUSION: Low back pain is common among Chinese miners. There were strong
      associations with occupational factors.

PMID- 22375936
TI  - Supreme Court review of the health care reform law.

PMID- 22375935
TI  - The virulent Wolbachia strain wMelPop increases the frequency of apoptosis in the
      female germline cells of Drosophila melanogaster.
AB  - BACKGROUND: Wolbachia are bacterial endosymbionts of many arthropod species in
      which they manipulate reproductive functions. The distribution of these bacteria
      in the Drosophila ovarian cells at different stages of oogenesis has been amply
      described. The pathways along which Wolbachia influences Drosophila oogenesis
      have been, so far, little studied. It is known that Wolbachia are abundant in the
      somatic stem cell niche of the Drosophila germarium. A checkpoint, where
      programmed cell death, or apoptosis, can occur, is located in region 2a/2b of the
      germarium, which comprises niche cells. Here we address the question whether or
      not the presence of Wolbachia in germarium cells can affect the frequency of cyst
      apoptosis in the checkpoint. RESULTS: Our current fluorescent microscopic
      observations showed that the wMel and wMelPop strains had different effects on
      female germline cells of D. melanogaster. The Wolbachia strain wMel did not
      affect the frequency of apoptosis in cells of the germarium. The presence of the
      Wolbachia strain wMelPop in the D. melanogasterw1118 ovaries increased the number
      of germaria where cells underwent apoptosis in the checkpoint. Based on the
      appearance in the electron microscope, there was no difference in morphological
      features of apoptotic cystocytes between Wolbachia-infected and uninfected flies.
      Bacteria with normal ultrastructure and large numbers of degenerating bacteria
      were found in the dying cyst cells. CONCLUSIONS: Our current study demonstrated
      that the Wolbachia strain wMelPop affects the egg chamber formation in the D.
      melanogaster ovaries. This led to an increase in the number of germaria
      containing apoptotic cells. It is suggested that Wolbachia can adversely
      interfere either with the cystocyte differentiation into the oocyte or with the
      division of somatic stem cells giving rise to follicle cells and, as a
      consequence, to improper ratio of germline cells to follicle cells and,
      ultimately, to apoptosis of cysts. There was no similar adverse effect in D.
      melanogaster Canton S infected with the Wolbachia strain wMel. This was taken to
      mean that the observed increase in frequency of apoptosis was not the general
      effect of Wolbachia on germline cells of D. melanogaster, it was rather induced
      by the virulent Wolbachia strain wMelPop.

PMID- 22375937
TI  - Vaccine-like controlled-release delivery of an immunomodulating peptide to treat
      experimental autoimmune encephalomyelitis.
AB  - The objective of this work is to use colloidal gel from alginate-chitosan-PLGA
      complex to deliver Ac-PLP-BPI-NH2-2 peptide in a controlled-release manner as a
      vaccine-like therapeutic to suppress experimental autoimmune encephalomyelitis
      (EAE) in the mouse model. Oppositely charged PLGA nanoparticles were prepared by
      a solvent diffusion method. The carboxyl group of the alginate and the amine
      group of the chitosan coated the nanoparticles with negative and positive
      charges, respectively. The peptide (Ac-PLP-BPI-NH2-2), designed to bind to MHC-II
      and ICAM-1 simultaneously, was formulated into the colloidal gel by physical
      mixture. Vaccine-like administration of the peptide-loaded colloidal gel (Ac-PLP
      BPI-NH2-2-NP) was achieved by subcutaneous (sc) injection to EAE mice. Disease
      severity was measured using clinical scoring and percent change in body weight.
      Cytokine production was determined using the splenocytes from Ac-PLP-BPI-NH2-2-NP
      treated mice and compared to that of controls. Ac-PLP-BPI-NH2-2-NP suppressed and
      delayed the onset of EAE as well as Ac-PLP-BPI-NH2-2 when delivered in a vaccine
      like manner. IL-6 and IL-17 levels were significantly lower in the Ac-PLP-BPI-NH2
      2-NP-treated mice compared to the mouse group treated with blank colloidal gel,
      suggesting that the mechanism of suppression of EAE is due to a shift in the
      immune response away from Th17 production. The results of this study suggest that
      a one-time sc administration of Ac-PLP-BPI-NH2-2 formulated in a colloidal gel
      can produce long-term suppression of EAE by reducing Th17 proliferation.

PMID- 22375939
TI  - A fast strong coupling algorithm for the partitioned fluid-structure interaction
      simulation of BMHVs.
AB  - The numerical simulation of Bileaflet Mechanical Heart Valves (BMHVs) has gained
      strong interest in the last years, as a design and optimisation tool. In this
      paper, a strong coupling algorithm for the partitioned fluid-structure
      interaction simulation of a BMHV is presented. The convergence of the coupling
      iterations between the flow solver and the leaflet motion solver is accelerated
      by using the Jacobian with the derivatives of the pressure and viscous moments
      acting on the leaflets with respect to the leaflet accelerations. This Jacobian
      is numerically calculated from the coupling iterations. An error analysis is done
      to derive a criterion for the selection of useable coupling iterations. The
      algorithm is successfully tested for two 3D cases of a BMHV and a comparison is
      made with existing coupling schemes. It is observed that the developed coupling
      scheme outperforms these existing schemes in needed coupling iterations per time
      step and CPU time.

PMID- 22375940
TI  - Maternal deprivation in rats is associated with corticotrophin-releasing hormone
      (CRH) promoter hypomethylation and enhances CRH transcriptional responses to
      stress in adulthood.
AB  - Exposure to stress during early development causes long-lasting alterations in
      behaviour and hypothalamic pituitary adrenal (HPA) axis activity, including
      increased expression of corticotrophin-releasing hormone (CRH). To determine
      whether early-life stress causes epigenetic changes in the CRH promoter leading
      to increased CRH transcription, 8-week old female and male rats, subjected to
      maternal deprivation (MD) between days 2 and 13 post-birth, were studied for HPA
      axis responses to stress and CRH promoter methylation in the hypothalamic
      paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA). Plasma
      corticosterone and PVN CRH heteronuclear (hn)RNA responses to acute restraint
      stress were higher in MD rats of both sexes. DNA methylation analysis of the CRH
      promoter revealed a significantly lower percentage of methylation in two CpGs
      preceding (CpG1) and inside (CpG2) the cyclic AMP-response element (CRE) at -230
      bp in the CRH promoter in the PVN but not the CeA of MD rats. Gel-shift assays,
      using nuclear proteins from forskolin-treated hypothalamic 4B cells and CRH
      promoter CRE oligonucleotides, unmethylated or methylated at CpG1, revealed a
      strong band that was supershifted by phospho-cAMP response element-binding
      antibody. This band was 50% weaker using oligonucleotides methylated at CpG2
      (intra-CRE), or methylated at both CpG1 and CpG2. These findings demonstrate that
      HPA axis hypersensitivity caused by neonatal stress causes long-lasting enhanced
      CRH transcriptional activity in the PVN of both sexes. Hypomethylation of the CRH
      promoter CRE, a region critical for CRH transcriptional activation, could serve
      as a mechanism for the increased transcriptional responses to stress observed in
      MD rats.

PMID- 22375941
TI  - The contractile system as a negative regulator of the connexin 43 hemichannel.
AB  - The molecular mechanisms underlying the regulation of gap junction (GJ) channels
      based on the 43-kDa connexin isoform (Cx43) have been studied extensively. GJ
      channels are formed by the docking of opposed hemichannels in adjacent cells.
      Mounting data indicate that unopposed Cx43 hemichannels are also functional in
      the plasma membrane. However, our understanding of how Cx43-hemichannel opening
      and closing is regulated at the molecular level is only poorly understood. Recent
      work elucidated that actomyosin contractility inhibits potently Cx43
      hemichannels. It is known that intracellular Ca2+ exerts a bell-shaped-dependent
      effect on Cx43-hemichannel opening. While low-intracellular [Ca2+] (<500 nM)
      provokes opening of the channel, high-intracellular [Ca2+] (> 500 nM) favours
      closing of the channel. The mechanism underlying this negative regulation of Cx43
      hemichannel activity by high-intracellular [Ca2+] seems to be dependent on the
      activation of the actomyosin contractile system. The activity of Cx43
      hemichannels is critically controlled by molecular interactions between the
      intracellular loop and the C-terminal tail. These interactions are essential for
      Cx43-hemichannel opening in response to triggers such as cytosolic [Ca2+] rise or
      external [Ca2+] lowering. In this review, we present the hypothesis that the
      actomyosin contractile system can function as an important brake mechanism on
      Cx43-hemichannel opening. By controlling loop-tail interactions, the contractile
      system would prevent aberrant or excessive opening of Cx43 hemichannels.

PMID- 22375942
TI  - Association between viral hepatitis and erectile dysfunction: a population-based
      case-control analysis.
AB  - INTRODUCTION: Chronic liver diseases are often accompanied by hypogonadism,
      testicular atrophy, and a reduction in libido, all of which are factors that may
      contribute to the development of erectile dysfunction (ED). However, large-scaled
      studies investigating the association between ED and viral hepatitis are still
      sparse. AIM: This study aimed to estimate the association between ED and a prior
      diagnosis of viral hepatitis using a population-based dataset with a case-control
      design in Taiwan. METHODS: We identified 6,429 patients with ED as cases and
      randomly selected 32,145 subjects as controls. We used conditional logistic
      regression to compute the odds ratio (OR) for having previously received a
      diagnosis of viral hepatitis between cases and controls. MAIN OUTCOME MEASURE:
      The prevalence and odds of having been previously diagnosed with hepatitis B,
      hepatitis C, a coinfection with hepatitis B and C, and viral hepatitis of other
      etiology were calculated between cases and controls. RESULTS. Of the 38,574
      sampled subjects, 3,930 (10.2%) had viral hepatitis before the index date; viral
      hepatitis was found in 900 (14.0%) cases and in 3,030 (9.4%) controls. After
      adjusting for monthly income, geographic location, hypertension, diabetes,
      hyperlipidemia, hepatic steatosis, coronary heart disease, obesity, and alcohol
      abuse/alcohol dependence syndrome, cases were found to be more likely to have
      prior viral hepatitis than controls (OR = 1.51, 95% confidence interval [CI] =
      1.39-1.64, P < 0.001). A much higher proportion of coinfection with viral
      hepatitis B and C was additionally found among cases (OR = 1.84, 95% CI = 1.72
      1.97) than controls. CONCLUSIONS. We conclude that ED was associated with prior
      viral hepatitis, especially with a coinfection of hepatitis B and C, after
      adjusting for potential confounders.

PMID- 22375943
TI  - Upregulation of miR-22 promotes osteogenic differentiation and inhibits
      adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells
      by repressing HDAC6 protein expression.
AB  - Mesenchmal stem cells (MSCs) can be differentiated into either adipocytes or
      osteoblasts, and a reciprocal relationship exists between adipogenesis and
      osteogenesis. Multiple transcription factors and signaling pathways have been
      reported to regulate adipogenic or osteogenic differentiation, respectively, yet
      the molecular mechanism underlying the cell fate alteration between adipogenesis
      and osteogenesis still remains to be illustrated. MicroRNAs are important
      regulators in diverse biological processes by repressing protein expression of
      their targets. Here, miR-22 was found to regulate adipogenic and osteogenic
      differentiation of human adipose tissue-derived mesenchymal stem cells (hADMSCs)
      in opposite directions. Our data showed that miR-22 decreased during the process
      of adipogenic differentiation but increased during osteogenic differentiation. On
      one hand, overexpression of miR-22 in hADMSCs could inhibit lipid droplets
      accumulation and repress the expression of adipogenic transcription factors and
      adipogenic-specific genes. On the other hand, enhanced alkaline phosphatase
      activity and matrix mineralization, as well as increased expression of osteo
      specific genes, indicated a positive role of miR-22 in regulating osteogenic
      differentiation. Target databases prediction and validation by Dual Luciferase
      Reporter Assay, western blot, and real-time polymerase chain reaction identified
      histone deacetylase 6 (HDAC6) as a direct downstream target of miR-22 in hADMSCs.
      Inhibition of endogenous HDAC6 by small-interfering RNAs suppressed adipogenesis
      and stimulated osteogenesis, consistent with the effect of miR-22 overexpression
      in hADMSCs. Together, our results suggested that miR-22 acted as a critical
      regulator of balance between adipogenic and osteogenic differentiation of hADMSCs
      by repressing its target HDAC6.

PMID- 22375945
TI  - Relative bone width of the edentulous maxillary ridge. Clinical implications of
      digital assessment in presurgical implant planning.
AB  - BACKGROUND: Healthy, well-structured mucosa may clinically disguise atrophic
      jawbone in preimplant diagnosis. PURPOSE: To analyze bone width in relation to
      the complete ridge thickness comparing the anterior with the posterior edentulous
      maxilla. MATERIALS AND METHODS: Data of 52 patients (mean age 62 +/- 9 years) who
      were edentulous for at least 1 year and who received implant treatment were
      analyzed. Computed tomography (CT) scans were obtained and virtually analyzed in
      perpendicular sections of 12 maxillary positions (central and lateral incisors,
      canines, premolars, and first molars) using an implant planning software.
      Absolute thickness of complete jaw, bone, and mucosa were digitally measured at
      crestal and basal ridge levels allowing for relative bone width (B-rel)
      calculation. RESULTS: Mean B-rel at crestal levels was lower than at basal levels
      (38.6% vs 51.5%, p < .001). Bone width increased significantly (p < .001) in the
      posterior maxilla at both levels, whereas the thickness of palatal and buccal
      mucosa was considerably stable. Mean basal B-rel ranged from 49% (6.2 +/- 2.0 mm)
      at incisors to 59% (9.0 +/- 2.3 mm) at first molars (p < .001). Mean proportion
      of regions showing B-rel < 50% were 43% at basal and 80% at crestal levels.
      CONCLUSIONS: The osseous volume of a large edentulous ridge might be clinically
      overestimated in preimplant diagnosis, as the relative bone width was generally
      lower than 50%. Clinicians can use the present results of the virtual bone and
      mucosa measurements to have a better first estimation of the osseous proportion
      depending on the maxillary area. However, up to date implant therapy for the
      edentulous maxilla requires CT-based prosthetically driven implant planning and
      preferably combination with guided implant placement by transferring planning
      information to a surgical template.

PMID- 22375946
TI  - The identification of a sensitizing component used in the manufacturing of an ink
      ribbon.
AB  - Skin diseases including dermatitis constitute ~ 30% of all occupational
      illnesses, with a high incidence in the printing industry. An outbreak of contact
      dermatitis among employees at an ink ribbon manufacturing plant was investigated
      by scientists from the National Institute for Occupational Safety and Health
      (NIOSH). Employees in the process areas of the plant were exposed to numerous
      chemicals and many had experienced skin rashes, especially after the introduction
      of a new ink ribbon product. To identify the causative agent(s) of the
      occupational dermatitis, the murine local lymph node assay (LLNA) was used to
      identify the potential of the chemicals used in the manufacture of the ink ribbon
      to induce allergic contact dermatitis. Follow-up patch testing with the suspected
      allergens was conducted on exposed employees. Polyvinyl butyral, a chemical
      component used in the manufacture of the ink ribbon in question and other
      products, tested positive in the LLNA, with an EC3 of 3.6%, which identifies it
      as a potential sensitizer; however, no employees tested positive to this chemical
      during skin patch testing. This finding has implications beyond those described
      in this report because of occupational exposure to polyvinyl butyral outside of
      the printing industry.

PMID- 22375947
TI  - Provision of mental health services in resource-poor settings: a randomised trial
      comparing counselling with routine medical treatment in North Afghanistan (Mazar
      e-Sharif).
AB  - BACKGROUND: Psychosocial stress caused by war, ongoing conflict, lack of
      security, and restricted access to resources promotes mental suffering and
      diseases in many resource-poor countries. In an exemplary setting, the present
      study compares the efficacy of psychosocial counselling with routine
      pharmacological treatment in a randomised trial in Mazar-e-Sharif (Afghanistan).
      METHODS: Help seeking Afghan women (N = 61), who were diagnosed with mental
      health symptoms by local physicians either received routine medical
      treatment(treatment as usual) or psychosocial counselling (5-8 sessions)
      following a specifically developed manualised treatment protocol. Primary outcome
      measures were symptoms of depression and anxiety assessed before treatment and at
      follow-up using the Hopkins Symptom Checklist and the Mini-International
      Neuropsychiatric Interview. Secondary outcome measures were psychosocial
      stressors and coping mechanisms. RESULTS: At 3-month follow-up, psychosocial
      counselling patients showed high improvements with respect to the severity of
      symptoms of depression and anxiety. In addition, they reported a reduction of
      psychosocial stressors and showed an enhancement of coping strategies. At the
      same time, the severity of symptoms, the quantity of psychosocial stressors and
      coping mechanisms did not improve in patients receiving routine medical
      treatment. CONCLUSION: These results indicate that psychosocial counselling can
      be an effective treatment for mental illnesses even for those living in ongoing
      unsafe environments.

PMID- 22375948
TI  - Multi-component drug ADME/T and metabolic interactions.

PMID- 22375950
TI  - Ni- and Pd-catalyzed synthesis of substituted and functionalized allylic
      boronates.
AB  - Two highly efficient and convenient methods for the synthesis of functionalized
      and substituted allylic boronates are described. In one procedure, readily
      available allylic acetates are converted to allylic boronates catalyzed by
      Ni/PCy(3) or Ni/PPh(3) complexes with high levels of stereoselectivity and in
      good yields. Alternatively, the borylation can be accomplished with commercially
      available Pd catalysts [e.g., Pd(2)(dba)(3), PdCl(2), Pd/C], starting with easily
      accessed allylic halides.

PMID- 22375951
TI  - N-Terminal pyroglutamate formation of Abeta38 and Abeta40 enforces oligomer
      formation and potency to disrupt hippocampal long-term potentiation.
AB  - Pyroglutamate (pGlu)-modified amyloid peptides have been identified in sporadic
      and familial forms of Alzheimer's disease (AD) and the inherited disorders
      familial British and Danish Dementia (FBD and FDD). In this study, we
      characterized the aggregation of amyloid-beta protein Abeta37, Abeta38, Abeta40,
      Abeta42 and ADan species in vitro, which were modified by N-terminal pGlu (pGlu
      Abeta3-x, pGlu-ADan) or possess the intact N-terminus (Abeta1-x, ADan). The pGlu
      modification confers rapid formation of oligomers and short fibrillar aggregates.
      In accordance with these observations, the pGlu-modified Abeta38, Alphabeta40 and
      Alphabeta42 species inhibit hippocampal long term potentiation of synaptic
      response, but pGlu-Abeta3-42 showing the highest effect. Among the unmodified
      Abeta peptides, only Abeta1-42 exhibites such propensity, which was similar to
      pGlu-Abeta3-38 and pGlu-Abeta3-40. Likewise, the amyloidogenic peptide pGlu-ADan
      impaired synaptic potentiation more pronounced than N-terminal unmodified ADan.
      The results were validated using conditioned media from cultivated HEK293 cells,
      which express APP variants favoring the formation of Abeta1-x, Abeta3-x or N
      truncated pGlu-Abeta3-x species. Hence, we show that the ability of different
      amyloid peptides to impair synaptic function apparently correlates to their
      potential to form oligomers as a common mechanism. The pGlu-modification is
      apparently mediating a higher surface hydrophobicity, as shown by 1
      anilinonaphtalene-8-sulfonate fluorescence, which enforces potential to interfere
      with neuronal physiology.

PMID- 22375952
TI  - 2012 Beers Criteria.

PMID- 22375953
TI  - Low-level laser therapy influences mouse odontoblast-like cell response in vitro.
AB  - OBJECTIVE: The purpose of this study was to analyze the influence of two
      different irradiation times with 85 mW/cm(2) 830 nm laser on the behavior of
      mouse odontoblast-like cells. BACKGROUND DATA: The use of low-level laser therapy
      (LLLT) to stimulate pulp tissue is a reality, but few reports relate
      odontoblastic responses to irradiation in in vitro models. METHODS: Odontoblast
      like cells (MDPC-23) were cultivated and divided into three groups:
      control/nonirradiated (group 1); or irradiated with 85 mW/cm(2), 830 nm laser for
      10 sec (0.8 J/cm(2)) (group 2); or for 50 sec (4.2 J/cm(2)) (group 3) with a
      wavelength of 830 nm. After 3, 7, and 10 days, it was analyzed: growth curve and
      cell viability, total protein content, alkaline phosphatase (ALP) activity,
      calcified nodules detection and quantification, collagen immunolocalization,
      vascular endothelial growth factor (VEGF) expression, and real-time polymerase
      chain reaction (PCR) for DMP1 gene. Data were analyzed by Kruskall-Wallis test
      (alpha=0.05). RESULTS: Cell growth was smaller in group 2 (p<0.01), whereas
      viability was similar in all groups and at all periods. Total protein content and
      ALP activity increased on the 10th day with 0.8 J/cm(2) (p<0.01), as well as the
      detection and quantification of mineralization nodules (p<0.05), collagen, and
      VEGF expression (p<0.01). The expression of DMP1 increased in all groups (p<0.05)
      compared with control at 3 days, except for 0.8 J/cm(2) at 3 days and control at
      10 days. CONCLUSIONS: LLLT influenced the behavior of odontoblast-like cells; the
      shorter time/smallest energy density promoted the expression of odontoblastic
      phenotype in a more significant way.

PMID- 22375954
TI  - Analysis of intracellular expressed proteins of Mycobacterium tuberculosis
      clinical isolates.
AB  - BACKGROUND: Tuberculosis (TB) is the most threatening infectious disease
      globally. Although progress has been made to reduce global incidence of TB,
      emergence of multidrug resistant (MDR) TB threatens to undermine these advances.
      To combat the disease, novel intervention strategies effective against drug
      resistant and sensitive subpopulations of M. tuberculosis are urgently required
      as adducts in the present treatment regimen. Using THP-1 cells we have analyzed
      and compared the global protein expression profile of broth-cultured and
      intraphagosomally grown drug resistant and sensitive M.tuberculosis clinical
      isolates. RESULTS: On comparing the two dimensional (2-DE) gels, many proteins
      were found to be upregulated/expressed during intracellular state which were
      identified by matrix assisted laser desorption/ionization mass spectrometry
      (MALDI-MS). Four proteins (adenosylhomocysteinase, aspartate carbomyltransferase,
      putatitive thiosulfate sulfurtransferase and universal stress protein) were
      present in both intracellular MDR and sensitive isolates and three of these
      belonged to intermediary metabolism and respiration category. Two proteins
      (alanine dehydrogenase and adenosine kinase) of intracellular MDR isolate and two
      (glucose-6-phosphate isomerase and ATP synthase epsilon chain) of intracellular
      sensitive isolate belonged to intermediary metabolism and respiration category.
      One protein (Peroxidase/Catalase) of intracellular MDR and three (HSPX, 14 kDa
      antigen and 10 kDa chaperonin) of sensitive isolate belonged to virulence,
      detoxification and adaptation category. ESAT-6 of intracellular MDR belonged to
      cell wall and cell processes category. Two proteins (Antigen 85-C and Antigen 85
      A) of intracellular sensitive isolate were involved in lipid metabolism while
      probable peptidyl-prolyl cis-trans isomerase A was involved in information
      pathways. Four (Rv0635, Rv1827, Rv0036c and Rv2032) of intracellular MDR and two
      proteins (Rv2896c and Rv2558c) of sensitive isolate were hypothetical proteins
      which were functionally characterized using bioinformatic tools. Bioinformatic
      findings revealed that the proteins encoded by Rv0036, Rv2032c, Rv0635, Rv1827
      and Rv2896c genes are involved in cellular metabolism and help in intracellular
      survival. CONCLUSIONS: Mass spectrometry and bioinformatic analysis of both MDR
      and sensitive isolates of M. tuberculosis during intraphagosomal growth showed
      that majority of commonly upregulated/expressed proteins belonged to the cellular
      metabolism and respiration category. Inhibitors of the metabolic
      enzymes/intermediate can therefore serve as suitable drug targets against drug
      resistant and sensitive subpopulations of M. tuberculosis.

PMID- 22375955
TI  - Tub bathing improves thermoregulation of the late preterm infant.
AB  - OBJECTIVE: To compare body temperature of the late preterm infant after 24 hours
      of life at three time points before and after immersion tub bathing or sponge
      bathing. We hypothesized that late preterm infants achieve significantly improved
      thermoregulation when bathed by immersion tub bath compared to traditional sponge
      bathing. DESIGN: This study was a randomized controlled trial. SETTING: A large
      metropolitan teaching hospital in the northeastern United States. POPULATION:
      Late preterm infants (100) born between 35 and 36 6/7 weeks gestation, bathed in
      the well-baby nursery of a 30-bed mother/baby unit. METHODS: Infant participants
      were identified and informed consent was obtained from the parent. Infants were
      randomized into two groups: 50 bathed by sponge and 50 bathed by immersion tub.
      Infant body temperature was measured at three time points: 10 minutes prior to
      bathing, 10 minutes following bathing, and 30 minutes following bathing. RESULTS:
      Infants who were tub bathed experienced significantly less variability in body
      temperature and overall were warmer 10 minutes and 30 minutes following the bath
      compared to infants who were sponge bathed (p = .024). CONCLUSION: The study
      findings support the hypothesis that late preterm infants who are tub bathed
      experience significantly less body temperature variability and an overall higher
      body temperature following the bathing procedure.

PMID- 22375956
TI  - Taper PbZr(0.2)Ti(0.8)O3 nanowire arrays: from controlled growth by pulsed laser
      deposition to piezopotential measurements.
AB  - Single crystalline PbZr(0.2)Ti(0.8) (PZT) nanowires arrays (NWAs) with taper
      morphology were epitaxially grown on SrTiO(3) (STO) substrate using pulse laser
      deposition. The taper morphology was attributed to the overcoating of PZT layer
      via a lateral growth of PZT clusters/adatoms during PZT NW growth. The growth
      window for PZT film or nanowire was systematically studied at varied temperatures
      and pressures. The proposed growth mechanism of the taper PZT NWAs was
      investigated from a layer by layer growth via Frank-Van Der Merwe growth,
      followed by a formation of three-dimensional islands via Stranski-Krastanow
      growth, and then axial growth on the lowest energy (001) plane with growth
      direction of [001] via vapor-solid growth mechanism. However, under certain
      conditions such as at higher or lower pressure (>400 or <200 mTorr) or substrate
      temperatures (>850  degrees C and <725  degrees C), formation of the PZT NWs is
      suppressed while the epitaxial PZT thin film via the layer-by-layer growth
      remains. The controllable growth directions of the PZT NWAs on (001), (110), and
      (111) STO substrates were demonstrated. The piezopotential of the taper PZT NWAs
      using a conducting atomic force microscope with the average voltage output of ~18
      mV was measured. The theoretical piezopotential of a PZT NW was calculated to
      compare with the measured outputs, providing a comprehensively experimental and
      theoretical understanding of the piezoelectricity for the PZT NW.

PMID- 22375957
TI  - Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in
      SEGA-related conditions: a US national claims database study.
AB  - OBJECTIVES: To compare the prevalence rates of clinical conditions related to
      subependymal giant cell astrocytomas (SEGAs) before and after SEGA surgery among
      patients with tuberous sclerosis complex (TSC). METHODS: Based on three US
      national claims databases, we analyzed and compared the prevalence rates of 21
      SEGA-related conditions (including seizures, hydrocephalus, headaches and stroke
      or hemiparesis) in the six months preceding surgery with the rates in the second
      through sixth post-surgery months and in the seventh through twelfth post-surgery
      months among TSC patients who underwent SEGA surgery during 2000-2009. Repeated
      measures analysis with a bootstrapping method was used to assess the surgery
      impact. RESULTS: Patients (N = 47) had a mean age of 11.5 years at their first
      SEGA surgery, and 66% were male. Compared with the six months preceding surgery,
      the post-surgery prevalence rates increased by 23-26% for seizures, 21-26% for
      hydrocephalus, 17-19% for headache and 6-9% for stroke or hemiparesis (all p <
      0.05). Repeated measures analysis confirmed the impact of surgery on the
      prevalence rate of these five conditions (all p < 0.05). CONCLUSIONS: SEGA
      surgery has its important role in SEGA treatment. However, after SEGA surgery
      this group of TSC patients had increased prevalence rates of seizures,
      hydrocephalus, vision disorders, headaches, stroke or hemiparesis, and autism.
      Future research to examine the causes of these symptoms is imperative.
      LIMITATIONS: The study results have limitations in data source
      representativeness, coding accuracy, and study design.

PMID- 22375958
TI  - Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients
      with SEGA-related tuberous sclerosis complex: a national claims database
      analysis.
AB  - OBJECTIVE: To examine the outcomes following resection of subependymal giant cell
      astrocytoma (SEGA) among patients with SEGA-associated tuberous sclerosis complex
      (TSC). METHODS: Using three large US national healthcare claims databases, we
      retrospectively examined the outcomes of SEGA surgery among TSC patients who
      underwent SEGA surgery between 2000 and 2009. The examined outcomes were:
      prevalence rates of post-surgery SEGA, repeated SEGA surgery, and postoperative
      complications (surgical procedure complications, nervous system complications,
      postoperative infections, complications of subdural empyemas, and complications
      of epidural abscesses). Descriptive data analysis and two-sided one sample t-test
      for mean or proportion were used to assess the characteristics of patients and
      the outcomes of SEGA surgery. RESULTS: The selected patients (N = 47) had a mean
      age of 11.6 years at their first SEGA surgery and 66% were male. During the third
      through twelfth months following surgery, 34% had post-surgery SEGA (diagnosis)
      and 12% underwent repeated SEGA surgeries. During the first post-surgery year,
      48.9% of patients developed postoperative complications (34.0% had complications
      relating to the surgical procedure, 12.8% had nervous system complications, 6.4%
      developed postoperative infections, 17.0% had complications of subdural empyemas,
      and 2.1% had complications of epidural abscesses). CONCLUSIONS: SEGA surgery was
      associated with statistically significant risks of developing post-surgery SEGA,
      requiring repeated SEGA surgery and developing postoperative complications.
      Future efforts in reducing these outcomes, either through improving surgical
      procedures or through alternative treatments, are urgently needed. LIMITATIONS:
      This study has its limitation in data source representativeness and measurement
      accuracy.

PMID- 22375959
TI  - Unpacking rights in indigenous African societies: indigenous culture and the
      question of sexual and reproductive rights in Africa.
AB  - BACKGROUND: Modern declarations on human rights have often proceeded without
      reference to the cultural content of rights, the existence of rights in African
      indigenous backgrounds, and the embodiment of certain key rights in the community
      itself. This paper is an attempt at developing an 'inventory' of rights in
      African cultures as a prelude to the generation both of a holistic theory of
      rights as well as a research agenda that can recognize the multifaceted nature of
      rights. METHODS: We use an interpretive ethnographic approach built on three
      sources of data: 1) our continuing ethnographic work among two distinct ethnic
      groups in southeastern Nigeria - the Ubang and the Igbo; 2) informal
      conversational interviews with individuals from a range of African countries; and
      3) a review of relevant literature based on African cultures which provides a
      context for some of the issues we raise. RESULTS: An examination of selected
      indigenous rights, entitlements, or privileges among the Ubang and Igbo
      illustrates indigenous culture as a key, but often neglected, axis of rights, as
      a critical framework for understanding human relationships with rights, and as a
      resource for, and challenge to, contemporary programmatic efforts focusing on
      universalized notions of rights. Understanding or interpreting rights in African
      settings within the framework defined by contemporary human rights discourse
      poses steep challenges to making progress in the realization of sexual and
      reproductive rights. CONCLUSIONS: Despite the potential dangers of privileging
      group rights over individual rights, when important rights are vested in the
      community; rights, entitlements, and privileges can also be recognized through
      community experiences, and realized through engagement with communities. Building
      on communal conceptualizations of rights in order to realize an even wider range
      of rights remains a largely unexplored strategy which holds promise for the
      achievement of sexual and reproductive health rights.

PMID- 22375960
TI  - Sexual functioning and distress among premenopausal women with uncomplicated type
      1 diabetes.
AB  - INTRODUCTION: Current studies indicate that women with type 1 diabetes (T1DM)
      have a high prevalence of sexual disorders although data on the prevalence of
      sexual dysfunction are limited when sexual distress is included. AIM: The
      frequency and the possible correlates of distressful sexual disorders in a highly
      selected group of type 1 diabetic women. METHODS: The sexual function, sexual
      distress, and general health status were assessed in 44 premenopausal women with
      uncomplicated T1DM and 47 healthy controls, using the Female Sexual Function
      Index (FSFI), the Female Sexual Distress Scale (FSDS), and the General Health
      Questionnaire-28 (GHQ-28). MAIN OUTCOME MEASURES: The impact of sexual distress
      on the frequency of female sexual dysfunction (FSD). RESULTS: The frequency of
      sexual disorders according to the FSFI was significantly higher in diabetic
      compared to control women (25% vs. 8.5%, respectively, P < 0.05). Diabetic women
      had significantly lower median (first to third quartile) total FSFI score
      compared to control group (30.55 [26.08-33.08] vs. 33.50 [30.70-34.30], P =
      0.001). Desire, arousal, and satisfaction were the sexual domains significantly
      affected in the diabetic group. Diabetic women had significantly higher median
      (first to third quartile) FSDS score compared to control group (6.5 [2.3-15.8]
      vs. 4.0 [1.0-10.5] P = 0.043). FSD (combined pathological FSFI and FSDS scores)
      was present in higher proportion of diabetic women (15.9%) compared to controls
      (2.1%) (P = 0.020). GHQ-28 score was comparable between the groups. However, in
      the diabetic group, FSD was related with anxiety, depression, and low educational
      level. Diabetes-related factors were not associated with FSD. CONCLUSIONS: Pre
      menopausal women with uncomplicated T1DM have significantly higher frequency of
      FSD compared to healthy controls, when the criterion of sexual distress is
      included. Psychosomatic and contextual factors implicated in sexual distress are
      correlates of FSD.

PMID- 22375962
TI  - Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas.
AB  - BACKGROUND: The purpose of this study was to clarify the prognostic significance
      of peritumoral lymphocyte infiltration in the capsule of soft tissue sarcomas
      (STS). Multiple observations in preclinical and clinical studies have shown that
      the immune system has a role in controlling tumor growth and progression.
      Prognostic markers in potentially curable STS should guide therapy after surgical
      resection. The immune status at the time of resection may be important, but the
      prognostic significance of peritumoral lymphocytes is unknown. METHODS: Tissue
      microarrays from 80 patients with STS were constructed from duplicate cores of
      tissue from the tumor and the peritumoral capsule. Immunohistochemistry was used
      to evaluate the CD3+, CD4+, CD8+ and CD20+ lymphocytes in the tumor and the
      peritumoral capsule. RESULTS: In univariate analyses, increasing numbers of CD20+
      (P = 0.032) peritumoral lymphocytes were associated with a reduced disease free
      survival (DSS). In multivariate analyses, a high number of CD20+ peritumoral
      lymphocytes (P = 0.030) in the capsule was an independent negative prognostic
      factor for DSS. There were no such associations of lymphocyte infiltration in the
      tumor. CONCLUSIONS: A high density of CD20+ peritumoral lymphocytes is an
      independent negative prognostic indicator for patients with STS. Further research
      is needed to determine whether CD20 cells in the peritumoral capsule of STS may
      promote tumor invasion in the surrounding tissue and increase the metastatic
      potential.

PMID- 22375963
TI  - Probing the lower limit of lattice thermal conductivity in an ordered extended
      solid: Gd117Co56Sn112, a phonon glass-electron crystal system.
AB  - The discovery of novel materials with low thermal conductivity is paramount to
      improving the efficiency of thermoelectric devices. As lattice thermal
      conductivity is inversely linked to unit cell complexity, we set out to
      synthesize a highly complex crystalline material with glasslike thermal
      conductivity. Here we present the structure, transport properties, heat capacity,
      and magnetization of single-crystal Gd(117)Co(56)Sn(112), a complex material with
      a primitive unit cell volume of ~6858 A(3) and ~285 atoms per primitive unit cell
      (1140 atoms per face-centered cubic unit cell). The room temperature lattice
      thermal conductivity of this material is kappa(L) = 0.28 W/(m.K) and represents
      one of the lowest ever reported for a nonglassy or nonionically conducting bulk
      solid. Furthermore, this material exhibits low resistivity at room temperature,
      and thus represents a true physical system that approaches the ideal phonon glass
      electron crystal.

PMID- 22375964
TI  - Delayed larval development in Anopheles mosquitoes deprived of Asaia bacterial
      symbionts.
AB  - BACKGROUND: In recent years, acetic acid bacteria have been shown to be
      frequently associated with insects, but knowledge on their biological role in the
      arthropod host is limited. The discovery that acetic acid bacteria of the genus
      Asaia are a main component of the microbiota of Anopheles stephensi makes this
      mosquito a useful model for studies on this novel group of symbionts. Here we
      present experimental results that provide a first evidence for a beneficial role
      of Asaia in An. stephensi. RESULTS: Larvae of An. stephensi at different stages
      were treated with rifampicin, an antibiotic effective on wild-type Asaia spp.,
      and the effects on the larval development were evaluated. Larvae treated with the
      antibiotic showed a delay in the development and an asynchrony in the appearance
      of later instars. In larvae treated with rifampicin, but supplemented with a
      rifampicin-resistant mutant strain of Asaia, larval development was comparable to
      that of control larvae not exposed to the antibiotic. Analysis of the bacterial
      diversity of the three mosquito populations confirmed that the level of Asaia was
      strongly decreased in the antibiotic-treated larvae, since the symbiont was not
      detectable by PCR-DGGE (denaturing gradient gel electrophoresis), while Asaia was
      consistently found in insects supplemented with rifampicin plus the antibiotic
      resistant mutant in the diet, and in those not exposed to the antibiotic.
      CONCLUSIONS: The results here reported indicate that Asaia symbionts play a
      beneficial role in the normal development of An. stephensi larvae.

PMID- 22375965
TI  - Mindfulness based cognitive therapy improves frontal control in bipolar disorder:
      a pilot EEG study.
AB  - BACKGROUND: Cognitive processing in Bipolar Disorder is characterized by a number
      of attentional abnormalities. Mindfulness Based Cognitive Therapy combines
      mindfulness meditation, a form of attentional training, along with aspects of
      cognitive therapy, and may improve attentional dysfunction in bipolar disorder
      patients. METHODS: 12 euthymic BD patients and 9 control participants underwent
      record of electroencephalography (EEG, band frequency analysis) during resting
      states (eyes open, eyes closed) and during the completion of a continuous
      performance task (A-X version, EEG event-related potential (ERP) wave component
      analysis). The individuals with BD completed an 8-week MBCT intervention and
      record of EEG was repeated. RESULTS: (1) Brain activity, individuals with BD
      showed significantly decreased theta band power, increased beta band power, and
      decreased theta/beta ratios during the resting state, eyes closed, for frontal
      and cingulate cortices. Post MBCT intervention improvement over the right frontal
      cortex was seen in the individuals with BD, as beta band power decreased. (2)
      Brain activation, individuals with BD showed a significant P300-like wave form
      over the frontal cortex during the cue. Post MBCT intervention the P300-like
      waveform was significantly attenuated over the frontal cortex. CONCLUSIONS:
      Individuals with BD show decreased attentional readiness and activation of non
      relevant information processing during attentional processes. These data are the
      first that show, MBCT in BD improved attentional readiness, and attenuated
      activation of non-relevant information processing during attentional processes.

PMID- 22375966
TI  - Goal-oriented patient care--an alternative health outcomes paradigm.

PMID- 22375967
TI  - Shared decision making--pinnacle of patient-centered care.

PMID- 22375968
TI  - Defining "patient-centered medicine".

PMID- 22375969
TI  - What's the alternative? The worldwide web of integrative medicine.

PMID- 22375970
TI  - JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.
AB  - BACKGROUND: Treatment options for myelofibrosis are limited. We evaluated the
      efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1
      and 2 inhibitor, as compared with the best available therapy, in patients with
      myelofibrosis. METHODS: We assigned 219 patients with intermediate-2 or high-risk
      primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential
      thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available
      therapy. The primary end point and key secondary end point of the study were the
      percentage of patients with at least a 35% reduction in spleen volume at week 48
      and at week 24, respectively, as assessed with the use of magnetic resonance
      imaging or computed tomography. RESULTS: A total of 28% of the patients in the
      ruxolitinib group had at least a 35% reduction in spleen volume at week 48, as
      compared with 0% in the group receiving the best available therapy (P<0.001); the
      corresponding percentages at week 24 were 32% and 0% (P<0.001). At 48 weeks, the
      mean palpable spleen length had decreased by 56% with ruxolitinib but had
      increased by 4% with the best available therapy. The median duration of response
      with ruxolitinib was not reached, with 80% of patients still having a response at
      a median follow-up of 12 months. Patients in the ruxolitinib group had an
      improvement in overall quality-of-life measures and a reduction in symptoms
      associated with myelofibrosis. The most common hematologic abnormalities of grade
      3 or higher in either group were thrombocytopenia and anemia, which were managed
      with a dose reduction, interruption of treatment, or transfusion. One patient in
      each group discontinued treatment owing to thrombocytopenia, and none
      discontinued owing to anemia. Nonhematologic adverse events were rare and mostly
      grade 1 or 2. Two cases of acute myeloid leukemia were reported with the best
      available therapy. CONCLUSIONS: Continuous ruxolitinib therapy, as compared with
      the best available therapy, was associated with marked and durable reductions in
      splenomegaly and disease-related symptoms, improvements in role functioning and
      quality of life, and modest toxic effects. An influence on overall survival has
      not yet been shown. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov
      number, NCT00934544.).

PMID- 22375971
TI  - A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis.
AB  - BACKGROUND: Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has
      clinically significant activity in myelofibrosis. METHODS: In this double-blind
      trial, we randomly assigned patients with intermediate-2 or high-risk
      myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154
      patients). The primary end point was the proportion of patients with a reduction
      in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic
      resonance imaging. Secondary end points included the durability of response,
      changes in symptom burden (assessed by the total symptom score), and overall
      survival. RESULTS: The primary end point was reached in 41.9% of patients in the
      ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A
      reduction in spleen volume was maintained in patients who received ruxolitinib;
      67.0% of the patients with a response had the response for 48 weeks or more.
      There was an improvement of 50% or more in the total symptom score at 24 weeks in
      45.9% of patients who received ruxolitinib as compared with 5.3% of patients who
      received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as
      compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence
      interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug
      because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the
      placebo group. Among patients who received ruxolitinib, anemia and
      thrombocytopenia were the most common adverse events, but they rarely led to
      discontinuation of the drug (in one patient for each event). Two patients had
      transformation to acute myeloid leukemia; both were in the ruxolitinib group.
      CONCLUSIONS: Ruxolitinib, as compared with placebo, provided significant clinical
      benefits in patients with myelofibrosis by reducing spleen size, ameliorating
      debilitating myelofibrosis-related symptoms, and improving overall survival.
      These benefits came at the cost of more frequent anemia and thrombocytopenia in
      the early part of the treatment period. (Funded by Incyte; COMFORT-I
      ClinicalTrials.gov number, NCT00952289.).

PMID- 22375972
TI  - A randomized trial of nicotine-replacement therapy patches in pregnancy.
AB  - BACKGROUND: Nicotine-replacement therapy is effective for smoking cessation
      outside pregnancy and its use is widely recommended during pregnancy. We
      investigated the efficacy and safety of nicotine patches during pregnancy.
      METHODS: We recruited participants from seven hospitals in England who were 16 to
      50 years of age with pregnancies of 12 to 24 weeks' gestation and who smoked five
      or more cigarettes per day. Participants received behavioral cessation support
      and were randomly assigned to 8 weeks of treatment with active nicotine patches
      (15 mg per 16 hours) or matched placebo patches. The primary outcome was
      abstinence from the date of smoking cessation until delivery, as validated by
      measurement of exhaled carbon monoxide or salivary cotinine. Safety was assessed
      by monitoring for adverse pregnancy and birth outcomes. RESULTS: Of 1050
      participants, 521 were randomly assigned to nicotine-replacement therapy and 529
      to placebo. There was no significant difference in the rate of abstinence from
      the quit date until delivery between the nicotine-replacement and placebo groups
      (9.4% and 7.6%, respectively; unadjusted odds ratio with nicotine-replacement
      therapy, 1.26; 95% confidence interval, 0.82 to 1.96), although the rate was
      higher at 1 month in the nicotine-replacement group than in the placebo group
      (21.3% vs. 11.7%). Compliance was low; only 7.2% of women assigned to nicotine
      replacement therapy and 2.8% assigned to placebo used patches for more than 1
      month. Rates of adverse pregnancy and birth outcomes were similar in the two
      groups. CONCLUSIONS: Adding a nicotine patch (15 mg per 16 hours) to behavioral
      cessation support for women who smoked during pregnancy did not significantly
      increase the rate of abstinence from smoking until delivery or the risk of
      adverse pregnancy or birth outcomes. However, low compliance rates substantially
      limited the assessment of safety. (Funded by the National Institute for Health
      Research Health Technology Assessment Programme; Current Controlled Trials
      number, ISRCTN07249128.).

PMID- 22375973
TI  - Placebo-controlled trial of amantadine for severe traumatic brain injury.
AB  - BACKGROUND: Amantadine hydrochloride is one of the most commonly prescribed
      medications for patients with prolonged disorders of consciousness after
      traumatic brain injury. Preliminary studies have suggested that amantadine may
      promote functional recovery. METHODS: We enrolled 184 patients who were in a
      vegetative or minimally conscious state 4 to 16 weeks after traumatic brain
      injury and who were receiving inpatient rehabilitation. Patients were randomly
      assigned to receive amantadine or placebo for 4 weeks and were followed for 2
      weeks after the treatment was discontinued. The rate of functional recovery on
      the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating
      greater disability) was compared over the 4 weeks of treatment (primary outcome)
      and during the 2-week washout period with the use of mixed-effects regression
      models. RESULTS: During the 4-week treatment period, recovery was significantly
      faster in the amantadine group than in the placebo group, as measured by the DRS
      score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit
      with respect to the primary outcome measure. In a prespecified subgroup analysis,
      the treatment effect was similar for patients in a vegetative state and those in
      a minimally conscious state. The rate of improvement in the amantadine group
      slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly
      slower than the rate in the placebo group (difference in slope, 0.30 points per
      week; P=0.02). The overall improvement in DRS scores between baseline and week 6
      (2 weeks after treatment was discontinued) was similar in the two groups. There
      were no significant differences in the incidence of serious adverse events.
      CONCLUSIONS: Amantadine accelerated the pace of functional recovery during active
      treatment in patients with post-traumatic disorders of consciousness. (Funded by
      the National Institute on Disability and Rehabilitation Research;
      ClinicalTrials.gov number, NCT00970944.).

PMID- 22375975
TI  - Images in clinical medicine. Eruptive xanthoma.

PMID- 22375974
TI  - A patient with asthma seeks medical advice in 1828, 1928, and 2012.

PMID- 22375976
TI  - Clinical problem-solving. A startling decline.

PMID- 22375977
TI  - Challenges facing JAK inhibitor therapy for myeloproliferative neoplasms.

PMID- 22375978
TI  - Nicotine replacement for smoking cessation during pregnancy.

PMID- 22375980
TI  - Intensive therapy and GFR in type 1 diabetes.

PMID- 22375981
TI  - Intensive therapy and GFR in type 1 diabetes.

PMID- 22375982
TI  - Intensive therapy and GFR in type 1 diabetes.

PMID- 22375984
TI  - Emergency hospitalizations for adverse drug events.

PMID- 22375985
TI  - Emergency hospitalizations for adverse drug events.

PMID- 22375987
TI  - Primary hyperparathyroidism.

PMID- 22375989
TI  - Ulcerative colitis.

PMID- 22375990
TI  - Ulcerative colitis.

PMID- 22375991
TI  - Ulcerative colitis.

PMID- 22375993
TI  - More on acutely injured patients receiving dabigatran.

PMID- 22375994
TI  - Bleeding risk with dabigatran in the frail elderly.

PMID- 22375995
TI  - Vemurafenib sensitivity skin reaction after ipilimumab.

PMID- 22375998
TI  - Images in clinical medicine. Hemotympanum.

PMID- 22376002
TI  - Asymmetric synthesis of gamma-nitroesters by an organocatalytic one-pot strategy.
AB  - An enantioselective synthesis of gamma-nitroesters by a one-pot asymmetric
      Michael addition/oxidative esterification of alpha,beta-unsaturated aldehydes is
      presented. The procedure is based on merging the enantioselective organocatalytic
      nitroalkane addition with an N-bromosuccinimide-based oxidation. The gamma
      nitroesters are obtained in good yields and enantioselectivities, and the method
      provides an attractive entry to optically active gamma-aminoesters, 2
      piperidones, and 2-pyrrolidones.

PMID- 22376001
TI  - Absence of linkage disequilibria between chromosomal arrangements and mtDNA
      haplotypes in natural populations of Drosophila subobscura from the Balkan
      Peninsula.
AB  - The genetic structure of Drosophila subobscura from the Balkan Peninsula was
      studied with respect to restriction site polymorphism of mitochondrial DNA in
      populations from the Derventa River Gorge and Sicevo Gorge (Serbia). To
      investigate the role of cytonuclear interactions in shaping mitochondrial DNA
      variability in natural populations of this species, the study was complemented
      with the analysis of linkage disequilibria between mitochondrial haplotypes and
      chromosomal inversion arrangements. Similar to other populations of D.
      subobscura, two main haplotypes (I and II) were found, as well as a series of
      less common ones. The frequencies of haplotypes I and II accounted for 25.8% and
      71.0%, respectively, in the population from the Derventa River Gorge, and for
      32.4% and 58.1%, respectively, in the population from Sicevo Gorge. One of the
      haplotypes harbored a large insertion (2.7 kb) in the A+T rich region. The
      frequency distribution of both haplotypes did not depart from neutrality.
      Contrary to prior studies, we did not detect any significant linkage
      disequilibrium between the two most frequent mtDNA haplotypes and any of the
      chromosomal arrangements in either of the populations. We conclude that linkage
      disequilibrium is not a general occurrence in natural populations of D.
      subobscura, and we discuss how transient coadaptations, ecologically specific
      selective pressures, and demographics could contribute to population-specific
      patterns of linkage disequilibrium.

PMID- 22376003
TI  - 2012 American Geriatrics Society Beers Criteria: new year, new criteria, new
      perspective.

PMID- 22376004
TI  - The effect of repeated torque in small diameter implants with machined and
      premachined abutments.
AB  - BACKGROUND: Detorquing value is an important factor in the amount of preload
      stresses during abutment screw fastening. This study evaluated the percentage of
      detorque values in two-piece machined titanium and premachined cast abutments in
      small diameter implants. MATERIALS AND METHODS: Three groups of five samples were
      evaluated. Group 1 (G1), machined titanium abutments, group 2 (G2), premachined
      cast straight abutments that cast with gold-palladium, and group 3 (G3),
      premachined angled cast abutments that cast with the same alloy, were angled
      before casting. Each abutment was torque to 24 Ncm according to the
      manufacturer's instructions and detorqued five times. The means of detorquing and
      torquing values in all groups were recorded. The mean of detorque in each group
      as a percentage of the toque value was calculated. The data for all groups were
      compared and calculated using analysis of variance (ANOVA) and t-test. RESULTS:
      Mean detorque values in G1, G2, and G3 were 88.1 +/- 1.69, 93.1 +/- 2.68, and
      80.9 +/- 4.95%, respectively. The ANOVA showed significant differences in mean of
      applied detorque (p < .001) and torque (p = .06) tightening among different
      groups. G2 had significantly greater detorque values (p < .05). No significant
      differences were found between G1 and G2. Surprisingly, abutment screw fracture
      occurred in three samples of G3. CONCLUSIONS: G3 showed significant percentage
      torque reduction (p < .05) and exhibited abutment screw fracture during
      evaluation. G2 presented the lowest torque reduction. Screw fracture occurred
      only in G3.

PMID- 22376005
TI  - Improved size-tunable synthesis of monodisperse gold nanorods through the use of
      aromatic additives.
AB  - We report an improved synthesis of colloidal gold nanorods (NRs) by using
      aromatic additives that reduce the concentration of hexadecyltrimethylammonium
      bromide surfactant to ~0.05 M as opposed to 0.1 M in well-established protocols.
      The method optimizes the synthesis for each of the 11 additives studied, allowing
      a rich array of monodisperse gold NRs with longitudinal surface plasmon resonance
      tunable from 627 to 1246 nm to be generated. The gold NRs form large-area ordered
      assemblies upon slow evaporation of NR solution, exhibiting liquid crystalline
      ordering and several distinct local packing motifs that are dependent upon the
      NR's aspect ratio. Tailored synthesis of gold NRs with simultaneous improvements
      in monodispersity and dimensional tunability through rational introduction of
      additives will not only help to better understand the mechanism of seed-mediated
      growth of gold NRs but also advance the research on plasmonic metamaterials
      incorporating anisotropic metal nanostructures.

PMID- 22376006
TI  - Contrasting snus and NRT as methods to quit smoking. an observational study.
AB  - BACKGROUND: Snus is considerably less hazardous to health than cigarettes. Recent
      data from Scandinavia have indicated that many smokers use snus as a method for
      quitting smoking. METHODS: Data from five repeated cross-sectional surveys of
      Norwegian men and women aged 16-74 were pooled (N = 6 262). Respondents were
      asked about current and former smoking and snus use. Former daily smokers (N =
      1219) and current daily smokers who had tried to quit at least once (N = 1118)
      were asked about the method they had used at their latest quit attempt and how
      many quit attempts they had made. Former smokers were also requested to report
      what year they had made their final quit attempt. RESULTS: Snus was the most
      common method used for quitting smoking among men, while NRT was most often used
      among women. Stratifying the data according to year of quitting smoking (1945
      2007) indicated a significant increase in use of the methods for quitting asked
      about over time. Among men, this was largely due to an increase in the use of
      snus. Among male quitters under the age of 45 years, 45.8% of those who had used
      snus on their last attempt to quit were current non-smokers (OR = 1.61, CI 1.04
      2.29), while 26,3% of those who had used NRT were current non-smokers. 59.6% of
      successful quitters and 19.5% of unsuccessful quitters who had used snus as a
      method for quitting smoking had continued to use snus on a daily basis after
      quitting. CONCLUSION: Norwegian men frequently use snus as a method for quitting
      smoking whereas women are more likely to use NRT. The findings indicate that
      switching to snus can be an effective method for quitting smoking.

PMID- 22376007
TI  - Communication technologies and maternal interest in health-promotion information
      about postpartum weight and parenting practices.
AB  - OBJECTIVE: To describe postpartum women's access, perceived skill, confidence,
      and use of Internet and mobile technologies; their views about receiving health
      information about postpartum weight and parenting; and whether these factors
      varied by race/ethnicity or income level. DESIGN: Health survey of a stratified
      random sample. SETTING: County in central Texas. PARTICIPANTS: One hundred forty
      five (145) White/Anglo, African American, or Hispanic women of higher and lower
      income. RESULTS: Overall, 122 (84.1%) of respondents had access to a computer
      with an Internet connection at home and made daily use of the following: the
      Internet 77.6%, e-mail 75.4%, cell phone 97.1%, and text messaging 66.7%.
      Significant racial/ethnic and income differences occurred in home Internet
      access, frequency of Internet and e-mail use, and perceived confidence or skill
      favoring White/Anglo women over ethnic minority women, and those of higher over
      lower income. Overall, 35.9% of women expressed "a lot" of interest in an
      Internet-based weight loss program, 38.9% in a weight loss program sent by mail,
      44.8% in an Internet-based parenting advice, and 38.6% in parenting advice sent
      by mail. Women of higher and lower income differed significantly in their
      interest in three of the four types of health-promotion information and methods
      of delivery. CONCLUSION: Generally, women with lower income were more likely to
      express high interest in receiving health information related to parenting by
      mail than those of higher incomes, whereas women of higher incomes were more
      likely to express high interest in receiving weight loss and parenting
      information through the Internet.

PMID- 22376009
TI  - Provoked vestibulodynia--medical factors and comorbidity associated with
      treatment outcome.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is the most common cause of
      dyspareunia in young women. The etiology is unclear, and there is little
      knowledge of how to predict treatment outcome. AIM: The aim of this study was to
      identify medical factors associated with treatment outcome and coital pain in
      women with PVD. METHODS: Seventy women previously treated for PVD at a vulvar
      open care unit completed questionnaires and a quantitative sensory testing
      session. MAIN OUTCOME MEASURES: Concomitant bodily pain and treatment outcome
      were surveyed using a study specific questionnaire. Coital pain was rated on a
      visual analog scale (VAS), range 0-100. Psychometric screening was carried out
      using the Hospital Anxiety and Depression Scale. Pressure pain thresholds on the
      arm, leg, and in the vestibulum were measured using pressure algometers. RESULTS:
      Major improvement/complete recovery was more likely in PVD patients with a
      maximum of one other concomitant pain disorder compared with patients with four
      or more (odds ratio = 7.8, confidence interval: 1.2-49.4, P = 0.03). In a
      multiple linear regression model, the number of other pain disorders (P < 0.01)
      and a diagnosis of primary PVD (P = 0.04) were positively associated with the
      coital VAS pain score. Women with secondary PVD reported major
      improvement/complete recovery to a higher extent than women with primary PVD (z =
      2.11, P = 0.04). CONCLUSION: A successful treatment outcome was more likely in
      PVD patients with fewer other concomitant pain conditions. The number of other
      bodily pain conditions was also associated to the intensity of the coital pain.
      Additionally, the results indicate higher incomplete response rates to treatment
      in women with primary PVD compared with secondary PVD.

PMID- 22376010
TI  - Performance evaluation of Unified Medical Language System(r)'s synonyms expansion
      to query PubMed.
AB  - BACKGROUND: PubMed is the main access to medical literature on the Internet. In
      order to enhance the performance of its information retrieval tools, primarily
      non-indexed citations, the authors propose a method: expanding users' queries
      using Unified Medical Language System' (UMLS) synonyms i.e. all the terms
      gathered under one unique Concept Unique Identifier. METHODS: This method was
      evaluated using queries constructed to emphasize the differences between this new
      method and the current PubMed automatic term mapping. Four experts assessed
      citation relevance. RESULTS: Using UMLS, we were able to retrieve new citations
      in 45.5% of queries, which implies a small increase in recall. The new strategy
      led to a heterogeneous 23.7% mean increase in non-indexed citation retrieved. Of
      these, 82% have been published less than 4 months earlier. The overall mean
      precision was 48.4% but differed according to the evaluators, ranging from 36.7%
      to 88.1% (Inter rater agreement was poor: kappa = 0.34). CONCLUSIONS: This study
      highlights the need for specific search tools for each type of user and use
      cases. The proposed strategy may be useful to retrieve recent scientific
      advancement.

PMID- 22376008
TI  - Synthesis, X-ray analysis, and biological evaluation of a new class of stereopure
      lactam-based HIV-1 protease inhibitors.
AB  - In an effort to identify a new class of druglike HIV-1 protease inhibitors, four
      different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been
      synthesized, biologically evaluated, and cocrystallized. The impact of the tether
      length of the central spacer (two or three carbons) was also investigated. A
      compound with a shorter tether and (3R,4S) absolute configuration exhibited high
      activity with a K(i) of 2.1 nM and an EC(50) of 0.64 MUM. Further optimization by
      decoration of the P1' side chain furnished an even more potent HIV-1 protease
      inhibitor (K(i) = 0.8 nM, EC(50) = 0.04 MUM). According to X-ray analysis, the
      new class of inhibitors did not fully succeed in forming two symmetric hydrogen
      bonds to the catalytic aspartates. The crystal structures of the complexes
      further explain the difference in potency between the shorter inhibitors (two
      carbon spacer) and the longer inhibitors (three-carbon spacer).

PMID- 22376012
TI  - Enhanced bioavailability of a poorly water-soluble weakly basic compound using a
      combination approach of solubilization agents and precipitation inhibitors: a
      case study.
AB  - Poorly water-soluble weakly basic compounds which are solubilized in gastric
      fluid are likely to precipitate after the solution empties from the stomach into
      the small intestine, leading to a low oral bioavailability. In this study, we
      reported an approach of combining solubilization agents and precipitation
      inhibitors to produce a supersaturated drug concentration and to prolong such a
      drug concentration for an extended period of time for an optimal absorption,
      thereby improving oral bioavailability of poorly water-soluble drugs. A weakly
      basic compound from Johnson and Johnson Pharmaceutical Research and Development
      was used as a model compound. A parallel microscreening precipitation method
      using 96-well plates and a TECAN robot was used to assess the precipitation of
      the tested compound in the simulated gastric fluid (SGF) and the simulated
      intestinal fluid (SIF), respectively, for lead solubilizing agents and
      precipitation inhibitors. The precipitation screening results showed vitamin E
      TPGS was an effective solubilizing agent and Pluronic F127 was a potent
      precipitation inhibitor for the tested compound. Interestingly, the combination
      of Pluronic F127 with vitamin E TPGS resulted in a synergistic effect in
      prolonging compound concentration upon dilution in SIF. In addition, HPMC E5 and
      Eudragit L100-55 were found to be effective precipitation inhibitors for the
      tested compounds in SGF. Furthermore, optimization DOE study results suggested a
      formulation sweet spot comprising HPMC, Eudragit L 100-55, vitamin E TPGS, and
      Pluronic F127. The lead formulation maintained the tested compound concentration
      at 300 MUg/mL upon dilution in SIF, and more than 70% of the compound remained
      solubilized compared with the compound alone at <1 MUg/mL of its concentration.
      Dosing of the solid dosage form predissolved in SGF in dogs resulted in 52% of
      oral bioavailability compared to 26% for the suspension control, a statistically
      significant increase (p = 0.002). The enhanced oral bioavailability of the tested
      compound could be attributed to generation and prolongation of a supersaturated
      drug concentration in vivo by the solubilizing agents and precipitation
      inhibitors. The study demonstrates that the combination approach of
      solubilization agents and precipitation inhibitors provides improved oral
      bioavailability for a poorly water-soluble weakly basic compound.

PMID- 22376013
TI  - Should we treat children with Down syndrome and leukemia in the developing world?

PMID- 22376014
TI  - Pediatric non-Hodgkin lymphoma: a retrospective 14-year experience with Berlin
      Frankfurt-Munster (BFM) protocols from a tertiary care hospital in Serbia.
AB  - Use of current intensive chemotherapy protocols in pediatric non-Hodgkin lymphoma
      (NHL) in high-income countries resulted in event-free survival (EFS) rates
      ranging from 80 to 90%. The results are inferior in less privileged countries
      with limited resources for medical care. There are no reports about comprehensive
      data analysis in pediatric NHL in Serbia. A retrospective study was carried out
      at University Children's Hospital, Belgrade, in children aged less than 18 years
      diagnosed with non-Hodgkin lymphoma from 1997 to 2011. Fifty-seven children were
      eligible for analysis. Fourteen were diagnosed with lymphoblastic lymphoma, 38
      with mature B-cell NHL (B-NHL), and 5 with anaplastic large-cell lymphoma. Mean
      age at diagnosis was 9.2 years, with male to female ratio 2.35:1. Children were
      treated according to Berlin-Frankfurt-Munster (BFM) protocols. With median follow
      up of 59.3 months, 5-year probability of EFS was 84.1% for all patients, whereas
      overall survival was 93%. These results with BFM protocol administration,
      although inferior to leading international groups, reflect good treatment outcome
      in our patients. To the best of the authors' knowledge, this article presents the
      first results regarding treatment and survival of childhood NHL in Serbia.

PMID- 22376015
TI  - The Cameroon 2008 Burkitt lymphoma protocol: improved event-free survival with
      treatment adapted to disease stage and the response to induction therapy.
AB  - Treatment of endemic Burkitt lymphoma (BL) with cyclophosphamide (CPM) and
      intrathecal methotrexate (IT MTX) can cure 50% of patients. In this study,
      induction therapy with CPM and IT MTX was followed by consolidation chemotherapy
      adapted for stage, clinical response, and abdominal ultrasound findings. One
      hundred and twenty-nine consecutive patients with BL, 77 male and 52 female with
      a median age of 7.9 years, were treated in mission hospitals in Cameroon. The
      diagnosis rested on fine-needle aspirate (79%), biopsy, bone marrow,
      cerebrospinal fluid, abdominal ultrasound, and clinical examination. Six percent
      had St Jude stage I, 13% stage II, 72% stage III, and 12% stage IV disease. The
      abdomen (76%) and face (50%) were mainly involved. Induction chemotherapy was CPM
      40 mg/kg and IT MTX 12.5 mg and IT hydrocortisone 12.5 mg on days 1, 8, and 15.
      Stage I and II patients received CPM 60 mg/kg on day 29, and stage III patients
      CPM 60 mg/kg on days 29 and 43 if in remission on day 28. Stage IV patients and
      patients not in remission received CPM 60 mg/kg on days 29, 43, and 57 and 1.0
      g/m(2) MTX intravenous (IV) and vincristine 1.5 mg/m(2) IV on day 29. Event-free
      survival (EFS) at mean 365 days was 61% (n = 79) and 100% in stage I, 85% in
      stage II, 60% in stage III, and 27% in stage IV patients. Deaths (n = 24) were
      disease or treatment related and 26 patients relapsed (mean 135 days). Risk
      adapted treatment achieved 61% 1-year EFS.

PMID- 22376016
TI  - ALL-BFM 95 treatment in Turkish children with acute lymphoblastic leukemia-
      experience of a single center.
AB  - Little is known about the likelihood of curing children with high-dose
      chemotherapy regimens for treatment of childhood acute lymphoblastic leukemia
      (ALL) in Turkey. The authors here report their 13 years' experience with original
      ALL-BFM (Berlin-Franfurt-Munster) 95 protocol in a cohort of 140 Turkish children
      with ALL. Complete remission rate was 97.7% with a relapse rate of 12.9% and
      death rate 17.9% during a median follow-up of 69 months. The event-free survival
      (EFS), disease-free survival (DFS), and overall survival (OS) in these patients
      at 12 years were 75.0%, 87.1%, and 80.6%, respectively. These results show that
      ALL-BFM 95 protocol is equally applicable in the experienced centers, even in
      developing countries without substantial treatment-related toxicity. High rate of
      infection deaths are to be reduced with correct policies.

PMID- 22376017
TI  - Mediastinal masses in children: experience with 120 cases.
AB  - Primary mediastinal malignancies are rare tumors and can originate from any
      mediastinal organ or tissue such as thymic, neurogenic, lymphatic, germinal, or
      mesenchymal. The authors reviewed all cases of primary pediatric mediastinal
      masses diagnosed over a 25-year period to determine the pattern of presentation,
      the histology, and the outcome of the surgical treatment. In this study, 120
      primary pediatric mediastinal mass cases diagnosed between 1985 and 2011 are
      retrospectively evaluated according to their age, sex, symptoms, anatomical
      location, surgical treatment, and histopathological evaluation. The median age of
      the patients was 5.8 years. There were 34 benign and 86 malign tumors. Thirty
      patients were asymptomatic. Common symptoms in the patients were cough, dyspnea,
      fatigue, fever, abdomen pain, back pain, and neurological symptoms. According to
      their origins, they were presented as neurogenic tumors (38.3%), lymphomas
      (18.3%), undifferentiated sarcomas (15%), germ cell tumors (7.5%), and the other
      tumors (22%) thymic pathologies, lymphangiomas, rhabdomyosarcomas, lipomas,
      hemangiomas, and Wilms' tumor. Complete resection of the tumor was performed in
      86 patients, partial resection of the tumor was the intervention in 11 patients.
      In 23 patients, biopsy was undertaken. Because of the high incidence of
      asymptomatic or nonspecific presentation such as the upper airway disease, the
      presentation of a mediastinal mass in children may be challenging. Neurogenic
      tumors or lymphomas are indicating surgery, if possible complete resection, for
      both benign and malignant conditions. Although surgery is the mainstay of therapy
      for most mediastinal tumors, an experienced multidisciplinary approach is
      necessary.

PMID- 22376018
TI  - Iron deficiency anemia in children presenting with lymphoreticular malignancies
      and the effect of induction therapy.
AB  - There is scant information regarding iron deficiency in children with malignant
      disorders. Serum iron status of children with lymphoreticular malignancies (LRMs)
      at onset and at the end of induction therapy, compared to the normal population,
      was evaluated. Prospective cohort study conducted between July 2002 and March
      2004. Previously untreated children recently diagnosed with LRM were studied. Age
      matched controls were enrolled from follow-up and growth monitoring clinics.
      Hematological (complete blood counts and red cell indices) parameters and markers
      of iron status (serum iron, serum ferritin, total iron binding capacity) were
      estimated at presentation and at the end of remission induction therapy, that is,
      5 weeks after initial evaluation. Bone marrow iron store were only assessed in
      cases. Thirty-five children (31 with acute lymphoid leukemia, 2 with acute
      myeloid leukemia, and 2 with non-Hodgkin lymphoma; 27 boys and 8 girls; 2 to 12
      years of age) were evaluated in the study cohort. Anemia was documented in 80% of
      children with LRM. Iron deficiency was an important etiological factor. In the
      majority of cases therapy resulted in significant improvement towards
      normalization of deranged hematological parameters. This phenomenon could be
      attributed to enhanced quantity and quality of erythropoietic activity and red
      cell transfusions. The observation suggests that therapeutic iron supplements are
      not indicated in the majority of children on therapy for malignant disorders.
      Various hematological and body iron status parameters should be assessed on a
      case-by-case basis.

PMID- 22376019
TI  - Population pharmacokinetics of native Escherichia coli asparaginase.
AB  - The main aim of this analysis was to characterize the population pharmacokinetics
      of native Escherichia coli asparaginase (ASNase medac) in pediatric patients with
      previously untreated acute lymphoblastic leukemia. Secondary objective was to
      give further evidence for bioequivalence between ASNase medac and a new
      recombinant ASNase preparation. The authors reanalyzed 233 plasma samples from 16
      children treated according to the DCOG-ALL 10 protocol (5000 U/m(2) ASNase medac)
      using NONMEM. Subsequently, assessment of bioequivalence was performed by
      including the preparation as a categorical covariate into the PopPK model when
      analyzing data of both preparations (480 samples, 32 children). A linear 2
      compartment model with first-order elimination sufficiently described ASNase
      medac pharmacokinetics. The parameters found were as follows: total body
      clearance 0.13 L/h +/- 12.4% per 1.73 m(2), volume of distribution in the central
      compartment 4.11 L +/- 12.3% per 70 kg, volume of distribution in the peripheral
      compartment 1.63 L per 70 kg and intercompartmental clearance 0.106 L/h (mean +/-
      interindividual variability). A visual predictive check procedure and simulation
      of different dosages ASNase medac administered in the ALL-BFM protocol indicated
      adequate model performance. Assessment of bioequivalence provided a difference of
      about 14% in clearance of both preparations being too small to be considered as
      clinically relevant. A population pharmacokinetic model of ASNase medac in
      pediatric patients with previously untreated acute lymphoblastic leukemia was
      established. The model was able to describe asparaginase activity of different
      dosages in the ALL-BFM protocol and provides further evidence for bioequivalence
      between ASNase medac and a new recombinant asparaginase preparation.

PMID- 22376020
TI  - Use of romiplostim for primary immune thrombocytopenia in children.
AB  - Very little has been published on the use of romiplostim to treat primary immune
      thrombocytopenia (ITP), refractory to previous treatments, in children. The
      objective of this study was to determine its efficacy and safety in pediatric
      patients in a university general hospital. Retrospective, longitudinal
      observational study of pediatric patients on treatment with romiplostim. The
      principal efficacy variable was platelet count. Safety was evaluated by recording
      possible adverse reactions to the medication, monitoring the appearance of
      thrombosis, thrombocytopenia during dose reduction, hemorrhage, and
      myelodysplastic syndromes. Three patients in the authors' center have been
      treated with romiplostim (subcutaneous [SC], initial dose: 1 MUg/kg/week) for ITP
      refractory to various treatments: 1 with newly diagnosed ITP and 2 with chronic
      ITP. Patients were followed up for 27 to 39 weeks after starting treatment.
      Responses were achieved in 7 to 28 days, and complete responses were maintained
      for 37% to 91% of the follow-up period, with median platelet counts between 40 *
      10(3)/MUL and 215 * 10(3)/MUL. The adverse reactions observed during follow-up
      were headache and asthenia in one patient and mucocutaneous bleeding after dose
      suspension in another one. With regard to effectiveness, the response in the 3
      patients was varied. The drug was considered to be safe, as there were only mild
      adverse reactions. Although further studies and long-term follow-up are required,
      these results show that romiplostim could be considered an alternative to
      immunosuppressive therapies, such as rituximab, or splenectomy in refractory
      chronic ITP.

PMID- 22376021
TI  - Severe refractory thrombocytopenia, dengue hemorrhagic fever, and intravenous
      anti-D immune globulin.

PMID- 22376023
TI  - Human rights and reproductive health: political realities and pragmatic choices
      for married adolescent women living in urban slums, Bangladesh.
AB  - BACKGROUND: In Bangladesh, particularly in urban slums, married adolescent
      women's human rights to life, health, and reproductive and sexual health remain
      adversely affected because of the structural inequalities and political economic,
      social and cultural conditions which shape how rights are understood, negotiated
      and lived. METHODS: The focus of the research and methods was anthropological. An
      initial survey of 153 married adolescent women was carried out and from this
      group, 50 in-depth interviews were conducted with selected participants and, from
      the in-depth interviews, a further eight case studies of women and their families
      were selected for in-depth repeated interviews and case histories. RESULTS: This
      paper speaks of the unanticipated complexities when writing on reproductive
      rights for poor adolescent women living in the slums, where the discourses on
      'universal human rights' are often removed from the reality of adolescent women's
      everyday lives. Married adolescent women and their families remain extremely
      vulnerable in the unpredictable, crime-prone and insecure urban slum landscape
      because of their age, gender and poverty. Adolescent women's understanding of
      their rights such as the decision to marry early, have children, terminate
      pregnancies and engage in risky sexual behaviour, are different from the widely
      accepted discourse on rights globally, which assumes a particular kind of
      individual thinking and discourse on rights and a certain autonomy women have
      over their bodies and their lives. This does not necessarily exist in urban slum
      populations. CONCLUSIONS: The lived experiences and decisions made pertaining to
      sexual and reproductive health and 'rights' exercised by married adolescent
      women, their families and slum communities, allow us to reflect on the disconnect
      between the international legal human rights frameworks as applied to sexual and
      reproductive health rights, and how these are played out on the ground. These
      notions are far more complex in environments where married adolescent women and
      their families live in conditions of poverty and socioeconomic deprivation.

PMID- 22376024
TI  - Limiting values of the 15N chemical shift of the imidazole ring of histidine at
      high pH.
AB  - Tautomeric identification by direct observation of (15)N chemical shifts of the
      imidazole ring of histidine (His) has become a common practice in NMR
      spectroscopy. However, such applications require knowledge of the "canonical"
      limiting values of the (15)N chemical shift of the imidazole ring of His in which
      each form of His, namely, the protonated (H(+)) and the tautomeric N(epsilon2)-H
      and N(delta1)-H forms, respectively, is present to the extent of 100%. So far,
      the adopted canonical limiting values of the (15)N chemical shift have been those
      available from model compounds. Whether these canonical values reflect those of
      the individual pure forms of His is investigated here by carrying out an analysis
      of the second-order shielding differences, DeltaDelta = |Delta(epsilon) -
      Delta(delta) |, with Delta(xi) (xi = epsilon or delta) being the density
      functional theory (DFT)-computed average shielding differences between the two
      nitrogens of the imidazole ring of His in each pure tautomeric form. In the high
      pH limit, the results indicate that (i) the DeltaDelta values from the DFT
      computed shielding, but not from the commonly used canonical limiting values, are
      in closer agreement with those obtained with experimental chemical shift data
      from model compounds in solution and solid-state NMR; and (ii) the commonly used
      canonical limiting values of the (15)N chemical shifts lead to an average
      tautomeric equilibrium constant that differs by a factor of ~2.6 from the one
      computed by using DFT-based (15)N limiting values, raising concern about the
      practice of using canonical limiting (15)N values. This can be avoided by
      reporting tautomeric equilibrium constants computed by using only limiting (15)N
      values for the N(epsilon2)-H tautomer.

PMID- 22376026
TI  - Chlorhexidine decreases the risk of ventilator-associated pneumonia in intensive
      care unit patients: a randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVE: The aim was to evaluate whether oral swabbing with 0.2%
      chlorhexidine gluconate (CHX) decreases the risk of ventilator-associated
      pneumonia (VAP) in intensive care unit (ICU) patients. MATERIAL AND METHODS:
      Sixty-one dentate patients scheduled for invasive mechanical ventilation for at
      least 48 h were included in this randomized, double-blind, controlled study. As
      these patients were variably incapacitated, oral care was provided by swabbing
      the oral mucosa four times/d with CHX in the CHX group (29 patients) and with
      saline in the control group (32 patients). Clinical periodontal measurements were
      recorded, and lower-respiratory-tract specimens were obtained for microbiological
      analysis on admission and when VAP was suspected. Pathogens were identified by
      quantifying colonies using standard culture techniques. RESULTS: Ventilator
      associated pneumonia developed in 34/61 patients (55.7%) within 6.8 d. The VAP
      development rate was significantly higher in the control group than in the CHX
      group (68.8% vs. 41.4%, respectively; p = 0.03) with an odds ratio of 3.12 (95%
      confidence interval = 1.09-8.91). Acinetobacter baumannii was the most common
      pathogen (64.7%) of all species identified. There were no significant differences
      between the two groups in clinical periodontal measurements, VAP development
      time, pathogens detected or mortality rate. CONCLUSION: The finding of the
      present study, that oral care with CHX swabbing reduces the risk of VAP
      development in mechanically ventilated patients, strongly supports its use in
      ICUs and indeed the importance of adequate oral hygiene in preventing medical
      complications.

PMID- 22376025
TI  - Detection and characterization of Wolbachia infections in laboratory and natural
      populations of different species of tsetse flies (genus Glossina).
AB  - BACKGROUND: Wolbachia is a genus of endosymbiotic alpha-Proteobacteria infecting
      a wide range of arthropods and filarial nematodes. Wolbachia is able to induce
      reproductive abnormalities such as cytoplasmic incompatibility (CI), thelytokous
      parthenogenesis, feminization and male killing, thus affecting biology, ecology
      and evolution of its hosts. The bacterial group has prompted research regarding
      its potential for the control of agricultural and medical disease vectors,
      including Glossina spp., which transmits African trypanosomes, the causative
      agents of sleeping sickness in humans and nagana in animals. RESULTS: In the
      present study, we employed a Wolbachia specific 16S rRNA PCR assay to investigate
      the presence of Wolbachia in six different laboratory stocks as well as in
      natural populations of nine different Glossina species originating from 10
      African countries. Wolbachia was prevalent in Glossina morsitans morsitans, G.
      morsitans centralis and G. austeni populations. It was also detected in G.
      brevipalpis, and, for the first time, in G. pallidipes and G. palpalis
      gambiensis. On the other hand, Wolbachia was not found in G. p. palpalis, G.
      fuscipes fuscipes and G. tachinoides. Wolbachia infections of different
      laboratory and natural populations of Glossina species were characterized using
      16S rRNA, the wsp (Wolbachia Surface Protein) gene and MLST (Multi Locus Sequence
      Typing) gene markers. This analysis led to the detection of horizontal gene
      transfer events, in which Wobachia genes were inserted into the tsetse flies fly
      nuclear genome. CONCLUSIONS: Wolbachia infections were detected in both
      laboratory and natural populations of several different Glossina species. The
      characterization of these Wolbachia strains promises to lead to a deeper insight
      in tsetse flies-Wolbachia interactions, which is essential for the development
      and use of Wolbachia-based biological control methods.

PMID- 22376028
TI  - Formation of pearl-necklace monomorphic G-quadruplexes in the human CEB25
      minisatellite.
AB  - CEB25 is a human minisatellite locus, composed of slightly polymorphic 52
      nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the
      human population are heterozygous, carrying alleles ranging from 0.5  to 20 kb,
      maintained by mendelian inheritance but also subject to germline instability. To
      provide insights on the biological role of CEB25, we interrogated its structural
      features. We report the NMR structure of the G-quadruplex formed by the conserved
      26-nt G-rich fragment of the CEB25 motif. In K(+) solution, this sequence forms a
      propeller-type parallel-stranded G-quadruplex involving a 9-nt central double
      chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by
      an A.T Watson-Crick base pair and a potential G.A noncanonical base pair. These
      base pairs contribute to the stability of the overall G-quadruplexstructure, as
      measured by an increase of about 17 kcal/mol in enthalpy or 6  degrees C in
      melting temperature. Further, we demonstrate that such a monomorphic structure is
      formed within longer sequence contexts folding into a pearl-necklace structure.

PMID- 22376027
TI  - Knocking out the dopamine reuptake transporter (DAT) does not change the baseline
      brain arachidonic acid signal in the mouse.
AB  - BACKGROUND: Dopamine transporter (DAT) homozygous knockout (DAT(-/-)) mice have a
      10-fold higher extracellular (DA) concentration in the caudate-putamen and
      nucleus accumbens than do wildtype (DAT(+/+)) mice, but show reduced presynaptic
      DA synthesis and fewer postsynaptic D(2) receptors. One aspect of
      neurotransmission involves DA binding to postsynaptic D(2)-like receptors coupled
      to cytosolic phospholipase A(2) (cPLA(2)), which releases the second messenger,
      arachidonic acid (AA), from synaptic membrane phospholipid. We hypothesized that
      tonic overactivation of D(2)-like receptors in DAT(-/-) mice due to the excess DA
      would not increase brain AA signaling, because of compensatory downregulation of
      postsynaptic DA signaling mechanisms. METHODS: [1-(14)C]AA was infused
      intravenously for 3 min in unanesthetized DAT(+/+), heterozygous (DAT(+/-)), and
      DAT(-/-) mice. AA incorporation coefficients k* and rates J(in), markers of AA
      metabolism and signaling, were imaged in 83 brain regions using quantitative
      autoradiography; brain cPLA(2)-IV activity also was measured. RESULTS: Neither k*
      nor J(in) for AA in any brain region, or brain cPLA(2)-IV activity, differed
      significantly among DAT(-/-), DAT(+/-), and DAT(+/+) mice. CONCLUSIONS: These
      results differ from reported increases in k* and J(in) for AA, and in brain
      cPLA(2) expression, in serotonin reuptake transporter (5-HTT) knockout mice, and
      suggest that postsynaptic dopaminergic neurotransmission mechanisms involving AA
      are downregulated despite elevated DA in DAT(-/-) mice.

PMID- 22376030
TI  - Plant polyphenols and oral health: old phytochemicals for new fields.
AB  - Despite the protective role of diets rich in fruit plant polyphenols against some
      cancers and chronic degenerative and inflammatory diseases, insufficient emphasis
      has been placed on oral health. Numerous studies have aimed to ascertain the role
      of polyphenols in the prevention and treatment of oral diseases; however, even
      when in vitro evidence appears convincing, the same is not true for in vivo
      studies, and thus there is a general paucity of solid evidence based on animal
      and clinical trials. To the best of our knowledge, only two reviews of
      polyphenols and oral health have been published; however, neither considered the
      potential role of whole plant extracts, which contain mixtures of many
      polyphenols that are often not completely identified. In the present study, our
      main aim was to review the current state of knowledge (search period: January
      1965 to March 2011) on the effects of plant extracts/polyphenols on oral health.
      We found data on grapes, berries, tea, cocoa, coffee, myrtle, chamomile,
      honey/propolis, aloe extracts and the three main groups of polyphenols
      (stilbenes, flavonoids and proanthocyanidins). Their effects on caries,
      gingivitis, periodontal disease, candidiasis, oral aphtae, oral mucositis, oral
      lichen planus, leukoplakia and oral cancer were investigated. The data suggest
      that there is a lack of strong evidence, in particular regarding randomized
      clinical trials. However, a fascinating starting point has been provided by pre
      clinical studies that have shown interesting activities of polyphenols against
      the most common oral diseases (caries, periodontitis and candidiasis), as well as
      in oral cancer prevention.

PMID- 22376031
TI  - Converting peptides into drug leads by lipidation.
AB  - Lipidation is a posttranslational modification of proteins that has also found
      its use in designing peptide drugs. The presence of a lipid group in peptides
      modulates their hydrophobicity, secondary structures and self-assembling
      propensities while retaining their abilities to bind to target receptors.
      Lipidation improves peptides' metabolic stability, membrane permeability,
      bioavailability, and changes peptides' pharmacokinetic and pharmacodynamic
      properties. Herein, we review the applications of various lipidation strategies
      in peptide drug design, the effects of the chain length and anchor position of
      fatty acids in peptide lipidation, the physicochemical and biological properties
      of selected lipidated peptides and the synthesis strategies for peptide
      lipidation.

PMID- 22376032
TI  - Privileged structures - dream or reality: preferential organization of
      azanaphthalene scaffold.
AB  - The concept of privileged structures/substructures (PS) is the idea that certain
      structural features produce biological effects more often than others. The PS
      method can be seen as an offspring of fragonomics, which is based on recent
      experimental measurements of protein-ligand interactions. If PS prove to be true,
      then chemical motives that enrich biological activity can be used when designing
      new drugs. However, PS remain controversial because we cannot be sure whether the
      excess of active structures does not result from an abundance in chemical
      libraries. In this review, we will focus, in particular, on the preferential
      organization of azanaphthalene scaffolds (AN) in drugs and natural products (NP),
      which are preferred by Nature in evolution. We will show that knowledge discovery
      in molecular databases can reveal interesting time-trends profiles for important
      classes of potentially privileged scaffolds. The chemical library of AN is
      dominated by monoaza-compounds, among which quinoline appears to be the most
      frequently investigated scaffold; however; more sophisticated database mining
      seems to indicate different PS patterns within the AN scaffold family.

PMID- 22376033
TI  - Role of ligand-based drug design methodologies toward the discovery of new anti-
      Alzheimer agents: futures perspectives in Fragment-Based Ligand Design.
AB  - Alzheimer's disease (AD), a degenerative disease affecting the brain, is the
      single most common source of dementia in adults. The cause and the progression of
      AD still remains a mystery among medical experts. As a result, a cure has not yet
      been discovered, even after decade's worth of research that started since 1906,
      when the disease was first identified. Despite the efforts of the scientific
      community, several of the biological receptors associated with AD have not been
      sufficiently studied to date, limiting in turn the design of new and more potent
      anti-AD agents. Thus, the search for new drug candidates as inhibitors of
      different targets associated with AD constitutes an essential part towards the
      discovery of new and more efficient anti-AD therapies. The present work is
      focused on the role of the Ligand-Based Drug Design (LBDD) methodologies which
      have been applied for the elucidation of new molecular entities with high
      inhibitory activity against targets related with AD. Particular emphasis is given
      also to the current state of fragment-based ligand approaches as alternatives of
      the Fragment-Based Drug Discovery (FBDD) methodologies. Finally, several
      guidelines are offered to show how the use of fragment-based descriptors can be
      determinant for the design of multi-target inhibitors of proteins associated with
      AD.

PMID- 22376034
TI  - Molecular property filters describing pharmacokinetics and drug binding.
AB  - Drug-target binding affinity and pharmacokinetics are equally important factors
      of drug design. Simple molecular properties such as molecular size have been used
      as pharmacokinetic and/or drug-likeness filters during chemical library design
      and also correlated with binding affinity. In the present study, current property
      filters are reviewed, a collection of their optimal values is provided, and a
      statistical framework is introduced allowing calibration of their selectivity and
      sensitivity for drugs. The role of ligand efficiency indices in drug design is
      also described. It is concluded that the usefulness of property filters of
      molecular size and lipophilicity is limited as predictors of general drug
      likeness. However, they demonstrate increased performance in specific cases, e.g.
      in central nervous system diseases, emphasizing their future importance in
      specific, disease-focused library design instead of general drug-likeness
      filtering.

PMID- 22376035
TI  - Molecular docking of opiates and opioid peptides, a tool for the design of
      selective agonists and antagonists, and for the investigation of atypical ligand
      receptor interactions.
AB  - In the last years, molecular docking emerged as a powerful tool to investigate
      the interactions between opioid ligands and their receptors, thus driving the
      design and development of new selective agonists or antagonists of therapeutic
      interest. This review especially covers the most representative and recent
      comparative molecular docking analyses of structurally related compounds, as well
      as of agonists and antagonists within the active and inactive states of the
      receptors. The comparative analyses gave important information on the structural
      determinants responsible for the affinity and selectivity of the ligands, and
      defined the features responsible for the activation of the receptors. A special
      section is dedicated to the analyses of recently discovered, unusual agonists
      lacking of the tyramine pharmacophore, such as Salvinorin A, and the
      cyclopeptides which comprise the D-Trp-Phe pharmacophoric motif. For the atypical
      structure of these compounds, the docking proved to be essential to disclose how
      they interact with and activate the receptors.

PMID- 22376036
TI  - Ion pore formation in lipid bilayers and related energetic considerations.
AB  - Interactions between membrane proteins (MPs)/antimicrobial peptides (AMPs) and
      lipids play important roles in the creation and function of membrane transport
      events like ion channels, defects, etc. Energetics based on these interactions
      have been found to explain various aspects of general drug effects on cell
      membranes. We have used various membrane active agents (MAAs) such as peptides,
      chemotherapy drugs, amphipathic molecules, amphiphiles, etc. to observe the
      complexes created between them and lipids in bilayers that often serve as
      membrane transport events in order to better understand the underlying
      mechanism(s). We find that the structures and functions of MAAs-lipids complexes
      are very specific to the respective MAAs. However, the underlying mechanisms
      originating from some common types of interactions are found to depend on
      physical properties of both MAAs and lipids. Specifically, the stability and
      functions of MAAs-lipid complexes depend primarily on the electrostatic energy
      coupling between MAAs and lipids. The mechanical energy coupling between MAAs and
      lipids, depending mainly on the bilayer elastic profiles, contributes just
      secondary effects into the stability and functions of the complexes. Both of
      these electrostatic and mechanical energetic couplings emerge from a unique
      interaction energy expression appearing from screened Coulomb interaction
      treatment between MAAs and lipids, mainly depending on the localized charge
      profiles and on other physical properties of both MAAs and lipids. This review
      will address the functions and underlying molecular mechanisms of membrane
      transport events, membrane effects of general drugs, etc. and thus will open up
      avenues leading to novel drug discovery.

PMID- 22376037
TI  - Possible involvement of angiogenesis in chronic liver diseases: interaction among
      renin-angiotensin-aldosterone system, insulin resistance and oxidative stress.
AB  - Angiogenesis plays a pivotal role in many pathological processes including
      chronic liver diseases. Various factors, such as renin-angiotensin-aldosterone
      system (RAAS), insulin resistance (IR), and reactive oxygen species (ROS)
      contribute reciprocally to promote angiogenesis. Blockade of RAAS by angiotensin
      converting enzyme inhibitor (ACE-I) or angiotensin II (AngII) receptor blocker
      (ARB) markedly attenuates liver fibrosis and hepatocellular carcinoma (HCC) along
      with suppression of angiogenesis, IR, and ROS. Aldosterone (Ald), a downstream
      component of AngII, is also involved in these processes, and a selective Ald
      blocker (SAB) significantly suppressed the progression of chronic liver diseases.
      The IR status itself has shown to directly accelerate the progression of chronic
      liver diseases whereas inhibition of ROS by iron chelator suppressed it through
      augmentation and inhibition of neovascularization. The combination therapy of ACE
      I/ARB/SAB with other clinically used agents, such as interferon, imatinib
      mesylate, vitamin K, iron chelator, and branched-chain amino acids (BCAA) exerted
      more potent inhibitory effects on the development of liver fibrosis and HCC than
      the treatment using a single agent alone. Collectively, the anti-angiogenic
      treatment targeting RAAS, IR, ROS with clinically available agents may become a
      new therapeutic strategy against the progression of chronic liver diseases.

PMID- 22376038
TI  - The protective effects of natural products on blood-brain barrier breakdown.
AB  - The blood-brain barrier (BBB) is a protective fence between the central nervous
      system and the systemic circulation, and is essential for maintaining the normal
      homeostasis of the central nervous system. BBB breakdown is instigated in many
      neurological disorders such as Alzheimer's disease and multiple sclerosis. Recent
      literature has advanced the knowledge on the physiology and pathophysiology of
      BBB breakdown, including the attribution of detrimental inducers and signalling
      transduction cascades. Natural products, such as flavonoids, phenolic compounds,
      terpenes, alkaloids, lipids and phthalides have been reported to attenuate many
      neurological diseases by modulating the signalling transduction cascades
      associated with BBB breakdown. Understanding the activities of these natural
      products through the molecular mechanisms associated with BBB breakdown will
      offer considerable scope in the discovery and development of novel agents for
      preventing BBB breakdown and thus, the progression of neurological disorders.

PMID- 22376039
TI  - Cognitive, psychological and psychiatric effects of ionizing radiation exposure.
AB  - Radiation exposure leads to an increased risk for cancer and, possibly,
      additional ill-defined non-cancer risk, including atherosclerotic,
      cardiovascular, cerebro-vascular and neurodegenerative effects. Studies of brain
      irradiation in animals and humans provide evidence of apoptosis, neuro
      inflammation, loss of oligo-dendrocytes precursors and myelin sheaths, and
      irreversible damage to the neural stem compartment with long-term impairment of
      adult neurogenesis. With the present paper we aim to present a comprehensive
      review on brain effects of radiation exposure, with a special focus on its impact
      on cognitive processes and psychological functions, as well as on their possible
      role in the pathophysiology of different psychiatric disorders.

PMID- 22376040
TI  - Gene-gene interactions between candidate gene polymorphisms are associated with
      total IgE levels in Korean children with asthma.
AB  - OBJECTIVE: To investigate associations between total serum immunoglobulin E (IgE)
      levels and single nucleotide polymorphisms (SNPs) from eight candidate genes (IL
      4 rs2243250, IL-4Ralpha rs1805010, IL-13 rs20541, IL-13Ralpha1 rs2495636, CD14
      rs2569190, tumor necrosis factor-alpha (TNF-alpha) rs1800629, cytotoxic T
      lymphocyte-associated antigen (CTLA4) rs231775, FCER1B rs1441585) in children
      with asthma and to evaluate gene-gene interactions. METHODS: A total of 669
      Korean children with asthma (n = 544 atopic n = 125 non-atopic) were included.
      Asthma phenotypes, total serum IgE levels, and methacholine challenge test
      results were evaluated. SNPs were genotyped using the polymerase chain reaction
      restriction fragment length polymorphisms (PCR-RFLP) method. Multi-factor
      dimensionality reduction (MDR) was used to analyze gene-gene interactions.
      RESULTS: The combination of the IL-13, IL-13Ralpha1, and CTLA4 polymorphisms was
      selected through MDR analysis of the data pertaining to children with atopic and
      non-atopic asthma (accuracy = 0.5459, cross validation consistency (CVC) =
      10/10). The IL-4Ralpha, IL-13, IL-13Ralpha1, CD14, and CTLA4 polymorphisms were
      selected as the best model of increased total serum IgE levels in non-atopic and
      atopic asthma (asthma: accuracy = 0.4726, CVC = 10/10; atopic asthma: accuracy =
      0.4573, CVC = 10/10). Both the IL-4Ralpha and the IL-13 polymorphisms were
      correlated with the IgE level. ANOVA analysis revealed that the combinations of
      the CTLA4 and IL-13, IL-13 and IL-13Ralpha1, IL-4Ralpha and IL-13, and CD14 and
      IL-13 polymorphisms were all significantly associated with increased total serum
      IgE levels. CONCLUSIONS: The best model of increased IgE level included the IL
      4Ralpha, IL-13, IL-13Ralpha1, CD14, and CTLA4 polymorphisms. Of the various
      interactions between these polymorphisms, the combinations of the CTLA4 and IL-13
      polymorphisms and the IL-13 and IL-13Ralpha1 polymorphisms showed synergistic
      effects in terms of increased total serum IgE levels in the present cohort.

PMID- 22376041
TI  - Same old Salmo? Changes in life history and demographic trends of North Iberian
      salmonids since the Upper Palaeolithic as revealed by archaeological remains and
      beast analyses.
AB  - Life history traits determine fitness and hence the ability of populations and
      species to survive through adverse conditions. Therefore, identifying temporal
      changes in life history traits over large timescales is necessary to understand
      and predict the effect of current global change on wild populations. In this
      study, we compare life history traits between Palaeolithic and present-day
      vertebrates, analysing the number of winters spent in the river and at sea by
      North Iberian salmonids (Salmo salar and Salmo trutta) from two separate time
      frames: the Upper Palaeolithic, based on archaeological remains, and the present
      day, based on sport catches. The river stage did not change significantly, but
      the marine period has been shortened in modern anadromous specimens, accordingly
      shortening mean generation time. Population growth rates have been estimated
      through Bayesian analyses of the mitochondrial DNA control region of modern
      specimens for the two Salmo species using two different mutation rates (1% and
      3.6%). Coincidence of coalescent N(e)  estimates with independent N(e) 
      calculated from catches suggests that the 3.6% mutation rate fits better the
      evolution of the studied populations. Population growth rate declines would have
      occurred in the last millennium and could be explained by a combination of
      climatic events and anthropogenic activities.

PMID- 22376042
TI  - Congruency of stereo lithographically produced surgical guide bases made from the
      same CBCT file: a pilot study.
AB  - PURPOSE: This is a pilot study evaluating the effect of the algorithms and
      production processes of four commercial manufacturers of stereolithographically
      produced surgical guide. MATERIALS AND METHODS: A singular Dicom file was used to
      produce six distinct duplicate dentures, which function as the base for surgical
      guides. The duplicate dentures were repeatedly fitted (n = 10) into an impression
      of the occlusal surface of the original scan appliance. The gaps between the
      incisal edge of teeth #8 and #9 and the corresponding imprints in the vinyl
      polysiloxane impression were photographed, digitally recorded, and measured in a
      blinded fashion. RESULTS: Nobel Biocare mean was 0.56 mm (range 0.49-0.65), I
      dent mean was 0.57 mm (range 0.31-0.74), Materialise II mean was 1.12 mm (range
      0.90-1.40), Blue Sky Bio II mean was 1.13 mm (range 0.93-1.35), Materialise I
      mean was 1.43 mm (range 1.21-1.86), and Blue Sky Bio I mean was 2.17 mm (range
      2.06-2.34). The difference between the fit of the Nobel Biocare and the I-dent
      guide bases and the guide bases from Materialise and Blue Sky Bio is
      statistically significant (p < .05). CONCLUSION: The algorithms and production
      processes of the different manufactures do influence the congruency outcome of
      the produced surgical guide bases. Within the limits of this study, we were
      unable to produce a perfect fit, although some duplicate dentures showed minimal
      errors. The implications of the discrepancies need further study.

PMID- 22376043
TI  - Evaluation of the Avahan HIV prevention initiative in India.

PMID- 22376044
TI  - Self-reported impulsivity, but not behavioral choice or response impulsivity,
      partially mediates the effect of stress on drinking behavior.
AB  - Stress and impulsivity contribute to alcohol use, and stress may also act via
      impulsivity to increase drinking behavior. Impulsivity represents a multi-faceted
      construct and self-report and behavioral assessments may effectively capture
      distinct clinically relevant factors. The present research investigated whether
      aspects of impulsivity mediate the effect of stress on alcohol use. A community
      based sample of 192 men and women was assessed on measures of cumulative stress,
      alcohol use, self-reported impulsivity, and behavioral choice and response
      impulsivity. Data were analyzed using regression and bootstrapping techniques to
      estimate indirect effects of stress on drinking via impulsivity. Cumulative
      adversity exhibited both direct effects and indirect effects (via self-reported
      impulsivity) on drinking behavior. Additional models examining specific types of
      stress indicated direct and indirect effects of trauma and recent life events,
      and indirect effects of major life events and chronic stressors on drinking
      behavior. Overall, cumulative stress was associated with increased drinking
      behavior, and this effect was partially mediated by self-reported impulsivity.
      Self-reported impulsivity also mediated the effects of different types of stress
      on drinking behavior. These findings highlight the value of mediation models to
      examine the pathways through which different types of stress increase drinking
      behavior. Treatment and prevention strategies should focus on enhancing stress
      management and self-control.

PMID- 22376045
TI  - Novel gene rearrangements in the mitochondrial genome of a webspinner, Aposthonia
      japonica (Insecta: Embioptera).
AB  - Webspinners (order Embioptera) are polyneopteran insects characterized by
      enlarged foretarsi with silk glands, whose silk is used to produce galleries in
      which the insects live gregariously. The phylogenetic position of webspinners has
      been debated. In the present study, an almost complete mitochondrial DNA (mtDNA)
      sequence of Embioptera is reported for the first time. The mtDNA of a webspinner,
      Aposthonia japonica , has the 13 protein-coding genes (PCGs) generally found in
      metazoan mtDNA sequences. There is a translocation of a large region including
      atp6, atp8, cox3, nad3, and nad5 as well as a duplication of the 12S rRNA gene.
      The rearrangement does not seem to affect nucleotide composition, although amino
      acid composition in some parts of the mtDNA is biased compared with other
      Polyneoptera species. Based on phylogenetic analyses using nucleotide sequences
      of all PCGs concatenated with two rRNA genes and the amino acid sequences of all
      PCGs, A. japonica is sister to Verophasmatodea, a suborder of typical stick and
      leaf insects.

PMID- 22376046
TI  - Atheromatous disease in small intracerebral vessels, microinfarcts and dementia.

PMID- 22376047
TI  - The Achilles tendon total rupture score: a study of responsiveness, internal
      consistency and convergent validity on patients with acute Achilles tendon
      ruptures.
AB  - BACKGROUND: The Achilles tendon Total Rupture Score was developed by a research
      group in 2007 in response to the need for a patient reported outcome measure for
      this patient population. Beyond this original development paper, no further
      validation studies have been published.Consequently the purpose of this study was
      to evaluate internal consistency, convergent validity and responsiveness of this
      newly developed patient reported outcome measure within patients who have
      sustained an isolated acute Achilles tendon rupture. METHODS: Sixty-four eligible
      patients with an acute rupture of their Achilles tendon completed the Achilles
      tendon Total Rupture Score alongside two further patient reported outcome
      measures (Disability Rating Index and EQ 5D). These were completed at baseline,
      six weeks, three months, six months and nine months post injury. The Achilles
      tendon Total Rupture Score was evaluated for internal consistency, using
      Cronbach's alpha, convergent validity, through correlation analysis and
      responsiveness, by analysing floor and ceiling effects and calculating its
      relative efficiency in comparison to the Disability Rating Index and EQ 5D
      scores. RESULTS: The Achilles tendon Total Rupture Score demonstrated high
      internal consistency (Cronbachs alpha > 0.8) and correlated significantly (p <
      0.001) with the Disability Rating Index at five time points (pre-injury, six
      weeks, three, six and nine months) with correlation coefficients between -0.5 and
      -0.9. However, the confidence intervals were wide. Furthermore, the ability of
      the new score to detect clinically important changes over time (responsiveness)
      was shown to be greater than the Disability Rating Index and EQ 5D. CONCLUSIONS:
      A universally accepted outcome measure is imperative to allow comparisons to be
      made across practice. This is the first study to evaluate aspects of validity of
      this newly developed outcome measure, outside of the developing centre. The ATRS
      demonstrated high internal consistency and responsiveness, with limited
      convergent validity. This research provides further support for the use of this
      outcome measure, however further research is required to advocate its universal
      use in patients with acute Achilles tendon ruptures. Such areas include inter
      rater reliability and research to determine the minimally clinically important
      difference between scores.All authors have read and concur with the content of
      this manuscript. The material presented has not been and will not be submitted
      for publication elsewhere, except as an abstract. All authors have made
      substantial contributions to all of the following: (1) the conception and design
      of the study, or acquisition of data, or analysis and interpretation of data, (2)
      drafting the article or revising it critically for important intellectual content
      and (3) final approval of the submitted version. This research has been funded by
      Arthritis Research UK, no conflicts of interests have been declared by the
      authors.

PMID- 22376048
TI  - American Geriatrics Society updated Beers Criteria for potentially inappropriate
      medication use in older adults.
AB  - Potentially inappropriate medications (PIMs) continue to be prescribed and used
      as first-line treatment for the most vulnerable of older adults, despite evidence
      of poor outcomes from the use of PIMs in older adults. PIMs now form an integral
      part of policy and practice and are incorporated into several quality measures.
      The specific aim of this project was to update the previous Beers Criteria using
      a comprehensive, systematic review and grading of the evidence on drug-related
      problems and adverse drug events (ADEs) in older adults. This was accomplished
      through the support of The American Geriatrics Society (AGS) and the work of an
      interdisciplinary panel of 11 experts in geriatric care and pharmacotherapy who
      applied a modified Delphi method to the systematic review and grading to reach
      consensus on the updated 2012 AGS Beers Criteria. Fifty-three medications or
      medication classes encompass the final updated Criteria, which are divided into
      three categories: potentially inappropriate medications and classes to avoid in
      older adults, potentially inappropriate medications and classes to avoid in older
      adults with certain diseases and syndromes that the drugs listed can exacerbate,
      and finally medications to be used with caution in older adults. This update has
      much strength, including the use of an evidence-based approach using the
      Institute of Medicine standards and the development of a partnership to regularly
      update the Criteria. Thoughtful application of the Criteria will allow for (a)
      closer monitoring of drug use, (b) application of real-time e-prescribing and
      interventions to decrease ADEs in older adults, and (c) better patient outcomes.

PMID- 22376049
TI  - Amine-modified graphene: thrombo-protective safer alternative to graphene oxide
      for biomedical applications.
AB  - Graphene and its derivatives have attracted significant research interest based
      on their application potential in different fields including biomedicine.
      However, recent reports from our laboratory and elsewhere have pointed to serious
      toxic effects of this nanomaterial on cells and organisms. Graphene oxide (GO)
      was found to be highly thrombogenic in mouse and evoked strong aggregatory
      response in human platelets. As platelets play a central role in hemostasis and
      thrombus formation, thrombotoxicity of GO potentially limits its biomedical
      applications. Surface chemistry of nanomaterials is a critical determinant of
      biocompatibility, and thus differentially functionalized nanomaterials exhibit
      varied cellular toxicity. Amine-modified carbon nanotubes have recently been
      shown to possess cytoprotective action, which was not exhibited by their
      relatively toxic carboxylated counterparts. We, therefore, evaluated the effect
      of amine modification of graphene on platelet reactivity. Remarkably, our results
      revealed for the first time that amine-modified graphene (G-NH(2)) had absolutely
      no stimulatory effect on human platelets nor did it induce pulmonary
      thromboembolism in mice following intravenous administration. Further, it did not
      evoke lysis of erythrocytes, another major cellular component in blood. These
      findings contrasted strikingly the observations with GO and reduced GO (RGO). We
      conclude that G-NH(2) is not endowed with thrombotoxic property unlike other
      commonly investigated graphene derivatives and is thus potentially safe for in
      vivo biomedical applications.

PMID- 22376050
TI  - Standard operating procedures: pubertas tarda/delayed puberty--male.
AB  - INTRODUCTION: Delayed puberty (DP) is a condition characterized by the lack of
      sexual maturation in boys (testis volume <4 mL) at a chronological age that is
      2.5 standard deviations above the mean age of puberty in a normal population.
      AIM: To review the etiology, pathogenesis diagnosis, and the available treatments
      for DP in males. METHODS: A systematic search of published evidence was performed
      using Medline (1969 to September 2011). MAIN OUTCOME MEASURES: The most important
      evidence regarding DP and the available treatment options were reviewed and
      discussed. Whenever possible, levels of evidence are reported. RESULTS: The
      prevalence of DP in 14-year-old boys in the United States is less than 2%, almost
      double of same figure in females. The etiology of DP is complex including
      genetic, functional, or nonidentifiable defects. The correct diagnosis should
      include an accurate medical history and physical examination along with specific
      laboratory tests. In addition, bone age radiographs are frequently helpful. If a
      specific disorder can be identified, therapy should be targeted at that disorder.
      Short-term testosterone therapy can be offered to boys with constitutional DP
      after a variable time of expectant observation essentially dictated by the
      patient's distress. Reassurance and continued observation, to ensure that the
      expected sexual maturation occurs, are often sufficient. In all other cases,
      exogenous gonadotropins, either recombinant or extracted, induce full gonadal
      maturation, while long-term testosterone therapy is the treatment of choice for
      hypergonadotropic hypogonadism or for hypothalamic or pituitary gonadotropin
      deficiency until fertility is attained. CONCLUSIONS: DP is a frequent condition
      that if not correctly diagnosed, may cause serious clinical and psychological
      consequences. Appropriate diagnosis and treatment provide normal pubertal
      development.

PMID- 22376053
TI  - Caries experience of chinese children with cleft lip and palate.
AB  - Objective : This study evaluated the caries experience in the primary teeth of
      children with and without cleft lip and palate (CLP). Design : Observational
      study. Setting : Dental hospital clinic. Patients : The sample consisted of 132
      pairs of Chinese children with and without CLP matched by gender, age, ethnicity,
      and socioeconomic status. Their ages were between 2 and 7 years. Methods : The
      children were dichotomized into 2- to 4-year-old (n  =  71) and 5- to 7-year-old
      groups (n  =  61). The oral examination was performed by one trained and
      calibrated dentist, and the caries experience was determined using the dmft
      (decay missing filled teeth) index. Results : For the 2- to 4-year-old group, the
      dmft values were 1.5 for the cleft group and 1.6 for the non-CLP group, but the
      difference was not statistically significant. For the 5- to 7-year-old group, the
      dmft indices were 5.2 for the cleft group compared with 2.9 for the control
      group; this difference was statistically significant (p  =  .0006). The caries
      rate for the various tooth types in the 5- to 7-year-old group was higher in the
      CLP group than in the non-CLP group; the most marked difference was for the
      lateral incisors, mandibular molars, and maxillary left first molars (p  = 
      .0001). Conclusions : The 5- to 7-year-old children with CLP had a higher caries
      experience in the primary dentition than the children without CLP. 

PMID- 22376051
TI  - Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor
      receptor 2 (VEGFR2) inhibitors. 1. Exploration of [5,6]-fused bicyclic scaffolds.
AB  - To develop RAF/VEGFR2 inhibitors that bind to the inactive DFG-out conformation,
      we conducted structure-based drug design using the X-ray cocrystal structures of
      BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various
      [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that
      forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of
      this anilide and the nitrogen atom on the six-membered ring of the scaffold was
      critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine
      derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid
      dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and
      showed significant suppression of ERK1/2 phosphorylation in an A375 melanoma
      xenograft model in rats by single administration. Tumor regression (T/C = -7.0%)
      in twice-daily repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d
      is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.

PMID- 22376054
TI  - FCl:PCX complexes: old and new types of halogen bonds.
AB  - MP2/aug'-cc-pVTZ calculations have been performed to investigate the halogen
      bonded complexes FCl:PCX, for X = NC, CN, F, H, CCH, CCF, CH(3), Li, and Na.
      Although stable complexes with a F-Cl...P halogen bond exist that form through
      the lone pair at P (configuration I), except for FCl:PCCN, the more stable
      complexes are those in which FCl interacts with the C=P triple bond through a
      perturbed pi system (configuration II). In complexes I, the nature of the halogen
      bond changes from traditional to chlorine-shared and the interaction energies
      increase, as the electron-donating ability of X increases. The anionic complex
      FCl:PC(-) has a chlorine-transferred halogen bond. SAPT analyses indicate that
      configuration I complexes with traditional halogen bonds are stabilized primarily
      by the dispersion interaction. The electrostatic interaction is the most
      important for configuration I complexes with chlorine-shared halogen bonds and
      for configuration II complexes except for FCl:PCNa for which the induction term
      is most important. The F-Cl stretching frequency is red-shifted upon
      complexation. EOM-CCSD/(qzp,qz2p) spin-spin coupling constants have been obtained
      for all FCl:PCX complexes with configuration I. (1)J(F-Cl) decreases upon
      complexation. (2X)J(F-P) values are quadratically dependent upon the F-P distance
      and are very sensitive to halogen-bond type. (1X)J(Cl-P) tends to increase as the
      Cl-P distance decreases but then decreases dramatically in the chlorine
      transferred complex FCl:PC(-) as the Cl-P interaction approaches that of a
      covalent Cl-P bond. Values of (1)J(F-Cl) for configuration II are reduced
      relative to configuration I, reflecting the longer F-Cl distances in II compared
      to those of the neutral complexes of I. Although the F-P and Cl-P distances in
      configuration II complexes are shorter than these distances in the corresponding
      configuration I complexes, (2X)J(F-P) and (1X)J(Cl-P) values are significantly
      reduced, indicating that coupling through the perturbed C-P pi bond is less
      efficient. The nature of F-P coupling for configuration II is also significantly
      different, as evidenced by the relative importance of PSO, FC, and SD components.

PMID- 22376055
TI  - A review of factors associated with unprotected sex among adult women in the
      United States.
AB  - OBJECTIVE: To provide an updated review of research since 2005 on factors
      associated with unprotected sex among women in the United States. DATA SOURCES:
      PubMed, CINAHL, and PsychINFO were searched from January 2006 through April 2011
      using the terms unsafe sex, sexual risk taking, contraception, contraception
      behavior, birth control, condoms, and condom utilization. STUDY SELECTION:
      Inclusion criteria included studies written in English on adult women in the
      United States age >= 18. Forty-five publications met inclusion criteria. DATA
      EXTRACTION: All factors associated with engagement in unprotected sex are
      presented. DATA SYNTHESIS: Unprotected sex has been associated with increasing
      age, being married, establishment of trust, recent experience of intimate partner
      violence, contraceptive side effects, infrequent sexual intercourse, and
      decreased arousal and pleasure due to contraceptive use. Religion, depression,
      history of abortion, number of children, having children, and number of
      pregnancies have not been associated with unprotected sex in recent studies.
      Several other variables have been studied with mixed results, possibly due to
      differences in research methods and sample characteristics. CONCLUSIONS: More
      research is needed to elucidate the impact of cultural factors, relationship
      factors, attitude to pregnancy and motherhood, and reproductive coercion on
      prevention of pregnancy and sexually transmitted infections. Nurses can lead
      research on these topics and implement evidence-based practice based on study
      findings.

PMID- 22376056
TI  - Horizontal transmission of the symbiotic bacterium Asaia sp. in the leafhopper
      Scaphoideus titanus Ball (Hemiptera: Cicadellidae).
AB  - BACKGROUND: Bacteria of the genus Asaia have been recently recognized as
      secondary symbionts of different sugar-feeding insects, including the leafhopper
      Scaphoideus titanus, vector of Flavescence doree phytoplasmas. Asaia has been
      shown to be localized in S. titanus gut, salivary glands and gonoducts and to be
      maternally transmitted to the progeny by an egg smearing mechanism. It is
      currently not known whether Asaia in S. titanus is transmitted by additional
      routes. We performed a study to evaluate if Asaia infection is capable of
      horizontal transmission via co-feeding and venereal routes. RESULTS: A Gfp-tagged
      strain of Asaia was provided to S. titanus individuals to trace the transmission
      pathways of the symbiotic bacterium. Co-feeding trials showed a regular transfer
      of bacterial cells from donors to recipients, with a peak of frequency after 72
      hours of exposure, and with concentrations of the administrated strain growing
      over time. Venereal transmission experiments were first carried out using
      infected males paired with uninfected females. In this case, female individuals
      acquired Gfp-labelled Asaia, with highest infection rates 72-96 hours after
      mating and with increasing abundance of the tagged symbiont over time. When
      crosses between infected females and uninfected males were conducted, the
      occurrence of "female to male" transmission was observed, even though the
      transfer occurred unevenly. CONCLUSIONS: The data presented demonstrate that the
      acetic acid bacterial symbiont Asaia is horizontally transmitted among S. titanus
      individuals both by co-feeding and venereal transmission, providing one of the
      few direct demonstrations of such a symbiotic transfer in Hemiptera. This study
      contributes to the understanding of the bacterial ecology in the insect host, and
      indicates that Asaia evolved multiple pathways for the colonization of S. titanus
      body.

PMID- 22376057
TI  - Ten years of negotiating rights around maternal health in Uttar Pradesh, India.
AB  - BACKGROUND: Preventable maternal mortality and morbidity have been globally
      recognized as human rights issues. Maternal mortality in India is among the
      highest in the world, and reflects inequity in access to healthcare: women from
      certain states as well as poorer women and less literate women appear to be
      significantly disadvantaged. The government of India has been attempting to
      improve maternal outcomes through a cash transfer within the National Rural
      Health Mission to encourage women to come to hospitals for childbirth. METHODS:
      This paper reviews documents of the last ten years describing the experiences of
      a Non-Governmental Organisation, SAHAYOG, in working with a civil society
      platform, the Healthwatch Forum, to develop 'rights based' strategies around
      maternal health. The paper builds an analysis using recent frameworks on
      accountability and gendered rights claiming to examine these experiences and draw
      out lessons regarding rights claiming strategies for poor women. RESULTS: The
      examination of documents over the last ten years indicates defined phases of
      development in the evolution of SAHAYOG's understanding and of the shifts in
      strategy among SAHAYOG and its close allies, and responses by the state. The
      first three stages depict the deepening of SAHAYOG's understanding of the manner
      in which poor and marginalized women negotiate their access to health care; the
      fourth stage explores a health system intervention and the challenges of working
      from within civil society in alliance with poor and marginalized women.
      CONCLUSION: The findings from SAHAYOG's experiences with poor Dalit women in
      Uttar Pradesh reveal the elements of social exclusion within the health system
      that prevent poor and marginalized women from accessing effective lifesaving
      care. Creating a voice for the most marginalised and carving space for its
      articulation impacts upon the institutions and actors that have a duty to meet
      the claims being made. However, given the accountability deficit, the analysis
      indicates the importance of going beyond the normative to developing actor
      oriented perspectives within rights based approaches, to take into account the
      complexity of the negotiating process that goes into claiming any kind of
      entitlements.

PMID- 22376058
TI  - Relationship between salivary antioxidant capacity and phases of the menstrual
      cycle.
AB  - BACKGROUND AND OBJECTIVE: Reactive oxygen species and free radicals are involved
      in the pathogenesis of periodontal disease. Previous studies have shown that the
      stage of the menstrual cycle is associated with the levels of gingival
      inflammation and discomfort. This study examined changes in salivary antioxidant
      activities, clinical parameters and bacterial levels during the menstrual cycle.
      MATERIAL AND METHODS: The study group consisted of 16 women with periodontitis
      and 12 healthy women. Clinical and bacterial measurements were performed for all
      subjects during the ovulatory and follicular phases. RESULTS: Salivary
      antioxidant activity during the ovulatory phase was significantly lower than
      during the follicular phase in the women with periodontitis. The antioxidant
      activity in all subjects during the ovulatory phase was negatively correlated
      with Prevotella intermedia (r = -0.430; p = 0.023) and total bacterial counts (r
      = -0.496; p = 0.007); however, these correlations were not significant for
      subjects in the follicular phase. CONCLUSION: This study showed that salivary
      antioxidant capacity decreased, while bleeding on probing and P. intermedia
      increased, over the course of the menstrual cycle in women with periodontitis.
      Antioxidant capacity could be involved in the pathogenesis of periodontitis.

PMID- 22376059
TI  - Rhodium(I)/diene-catalyzed addition reactions of arylborons with ketones.
AB  - Rh(I)/diene-catalyzed addition reactions of arylboroxines/arylboronic acids with
      unactivated ketones to form tertiary alcohols in good to excellent yields are
      described. By using C(2)-symmetric (3aR,6aR)-3,6-diaryl-1,3a,4,6a
      tetrahydropentalenes as ligands, the asymmetric version of such an addition
      reaction, with up to 68% ee, was also realized.

PMID- 22376060
TI  - Sufentanil versus fentanyl: efficacy and patient satisfaction with intrathecal
      pain management.
AB  - OBJECTIVES: This study compared fentanyl vs. sufentanil in intrathecal pain
      pumps. H1: both reduce patient subjective pain ratings. H2: sufentanil is more
      effective than fentanyl. H3: overall satisfaction with pain control is greater
      with sufentanil. MATERIALS/METHOD: This is an archival study of patients in
      tertiary pain management (N = 97, mean age = 58.77, standard deviation = 14.88).
      Pain was measured using the subjective units of discomfort scale. Satisfaction
      with pain control/relief was measured by asking patients each visit if they are
      satisfied with pain management and is recorded in a "yes"/ "no" manner. Pain
      ratings were analyzed with repeated measures analysis of variance and
      satisfaction was analyzed with chi square. RESULTS/DISCUSSION: Sufentanil was
      found to be marginally more effective, but both medications controlled a
      significant degree of variance in pain reduction over time. A significantly
      greater number of patients maintained on sufentanil were satisfied with care than
      patients on fentanyl.

PMID- 22376062
TI  - The community counts: a participatory approach to social audits. Introduction.

PMID- 22376063
TI  - Compositional space boundaries for organic compounds.
AB  - An upper elemental compositional boundary for fossil hydrocarbons has previously
      been established as double-bond equivalents (i.e., DBE = rings plus double bonds)
      not exceeding 90% of the number of carbons. For heteroatom-containing fossil
      compounds, the 90% rule still applies if each N atom is counted as a C atom. The
      90% rule eliminates more than 10% of the possible elemental compositions at a
      given mass for fossil database molecules. However, some synthetic compounds can
      fall outside the upper boundary defined for naturally occurring compounds. Their
      inclusion defines an "absolute" upper boundary as DBE (rings plus double bonds to
      carbon) equal to carbon number plus one, and applies to all organic compounds
      including fullerenes and other molecules containing no hydrogen. Finally, the DBE
      definition can fail for molecules with particular atomic valences. Therefore, we
      also present a generalized DBE definition that includes atomic valence to enable
      calculation of the correct total number of rings, double bonds, and triple bonds
      for heteroatom-containing compounds.

PMID- 22376061
TI  - Polar dibenzocyclooctynes for selective labeling of extracellular glycoconjugates
      of living cells.
AB  - Although strain-promoted alkyne-azide cycloadditions (SPAAC) have found wide
      utility in biological and material sciences, the low polarity and limited water
      solubility of commonly used cyclooctynes represent a serious shortcoming. To
      address this problem, an efficient synthetic route has been developed for highly
      polar sulfated dibenzocyclooctynylamides (S-DIBO) by a Friedel-Crafts alkylation
      of 1,2-bis(3-methoxyphenyl)ethylamides with trichlorocyclopropenium cation
      followed by a controlled hydrolysis of the resulting dichlorocyclopropenes to
      give bis(3-methoxyphenyl)cyclooctacyclopropenones, which were subjected to
      methoxy group removal of the phenols, O-sulfation, and photochemical unmasking of
      the cyclopropenone moiety. Accurate rate measurements of the reaction of benzyl
      azide with various dibenzylcyclooctyne derivatives demonstrated that aromatic
      substitution and the presence of the amide function had only a marginal impact on
      the rate constants. Biotinylated S-DIBO 8 was successfully used for labeling
      azido-containing glycoconjugates of living cells. Furthermore, it was found that
      the substitution pattern of the dibenzylcyclooctynes influences subcellular
      location, and in particular it has been shown that DIBO derivative 4 can enter
      cells, thereby labeling intra- and extracellular azido-modified glycoconjugates,
      whereas S-DIBO 8 cannot pass the cell membrane and therefore is ideally suited
      for selective labeling of cell surface molecules. The ability to selectively
      label cell surface molecules will yield unique opportunities for glycomic
      analysis and the study of glycoprotein trafficking.

PMID- 22376064
TI  - Suspending multi-walled carbon nanotubes by humic acids from a peat soil.
AB  - Suspension of the pristine and COOH-substituted multi-walled carbon nanotubes (P-
      and C-MWCNTs) with different outer diameters (ODs) by humic acids (HAs) from a
      peat soil was examined. Under shaking condition, MWCNTs were not suspended within
      5 d. Without HAs, C-MWCNTs were slightly suspended by sonication within 16 h, but
      no suspension was observed for the pristine ones (P-MWCNTs). HAs greatly enhanced
      suspension of both P- and C-MWCNTs. The suspension enhancement was attributed to
      HA sorption, which increased electrostatic repulsion and steric hindrance between
      individual MWCNTs. Introduction of O-containing hydrophilic moieties to MWCNTs
      via HA sorption enhanced the interactions of their surfaces with water through H
      bonding. Suspending capability of various MWCNTs on suspended mass concentration
      basis by four HAs showed inconsistent orders with the increasing or decreasing
      trend of their ODs. However, the suspended surface area concentrations of both P-
      and C-MWCNTs by individual HAs consistently followed an order of P8 > P30 > P50,
      and C8 > C30 > C50 (P and C, respectively, refer to P- and C-MWCNTs, and the
      numbers represent their ODs). These data implied that MWCNTs with smaller OD
      could be more strongly suspended by a given HA relative to those with larger OD
      under sonication condition.

PMID- 22376065
TI  - The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of
      protoporphyrin IX. Involvement of reactive oxygen species (ROS).
AB  - By exposing cells of the U118MG glioblastoma cell line to protoporphyrin IX
      (PPIX) in culture, we found that the 18 kDa mitochondrial translocator protein
      (TSPO) prevents intracellular accumulation of PPIX. In particular, TSPO knockdown
      by stable transfection of TSPO silencing siRNA vectors into U118MG cells leads to
      mitochondrial PPIX accumulation. In combination with light exposure, the PPIX
      accumulation led to cell death of the TSPO knockdown cells. In the sham control
      cells (stable transfection of scrambled siRNA vectors), TSPO expression remained
      high and no PPIX accumulation was observed. The prevention of PPIX accumulation
      by TSPO was not due to conversion of PPIX to heme in the sham control cells.
      Similar to TSPO knockdown, the reactive oxygen species (ROS) scavenger
      glutathione (GSH) also enhanced PPIX accumulation. This suggests that that ROS
      generation as modulated by TSPO activation may present a mechanism to prevent
      accumulation of PPIX.

PMID- 22376067
TI  - Malpositioned osseointegrated implants relocated with segmental osteotomies: a
      retrospective analysis of a multicenter case series with a 1- to 15-year follow
      up.
AB  - PURPOSE: This multicenter case series evaluates retrospectively the clinical
      outcomes of malpositioned implants surgically relocated in a more convenient
      position by segmental osteotomies. MATERIALS AND METHODS: Authors who published,
      on indexed journals or books, works about malpositioned implant correction by
      segmental osteotomies were contacted. Five centers, out of 11 selected, accepted
      to participate in this study. The dental records of patients who underwent
      implant relocation procedures were reviewed. Implant survival rates were analyzed
      and a blinded assessor examined clinical photos and periapical radiographs to
      evaluate esthetic outcome (pink esthetic score [PES]) and changes of marginal
      bone level over time. Patients were requested to fill a verbal rating scale form
      about discomfort, compliance, and satisfaction related to the procedure. RESULTS:
      Fifteen malpositioned implants relocated by segmental osteotomies were followed
      for a period ranging from 1 to 15 years (mean 6.0 +/- 3.9 years). The overall
      implant survival rate from baseline to the last follow-up visit was 100%. The
      mean marginal bone loss was 0.36 mm at the 12-month follow-up visit and no
      relevant further changes were observed at the following examinations. Significant
      esthetic improvement was recorded at 1-year examination with PES evaluation (p <
      .0001). Patients' feedback described this procedure as not excessively invasive
      and uncomfortable, reporting a high final satisfaction rate. CONCLUSIONS: The
      present study suggests that implant relocation with segmental osteotomies could
      be an effective alternative method to correct the position of unrestorable
      malpositioned implants in a single-stage surgery.

PMID- 22376068
TI  - Raman microscopy for noninvasive imaging of pharmaceutical nanocarriers:
      intracellular distribution of cationic liposomes of different composition.
AB  - Nanotechnology is playing an increasing role in targeted drug delivery into
      pathological tissues. Drug-loaded pharmaceutical nanocarriers can be delivered
      into diseased sites by passive targeting (spontaneous accumulation of
      nanocarriers in the areas with affected vasculature) or by active targeting (via
      site-specific ligands attached to the surface of drug-loaded nanocarriers).
      Subsequent level of targeting requires cellular internalization of nanocarriers
      and their specific association with certain individual cell organelles. The
      control over intracellular distribution of pharmaceutical nanocarriers requires
      effective and noninvasive methods of their visualization inside cells. In an
      attempt to enhance cellular internalization of pharmaceutical nanocarriers and
      their association with mitochondria specifically, we have prepared three types of
      cationic liposomes and investigated their intracellular distribution. The
      analysis was performed using Raman microspectroscopy in order to provide
      morphological information as well as biochemical signatures of the sample. It was
      demonstrated that Raman microscopy allows evaluation of the extent of
      mitochondrial association depending on the liposome composition.

PMID- 22376069
TI  - Parsimonious estimation of the Wechsler Memory Scale, Fourth Edition
      demographically adjusted index scores: immediate and delayed memory.
AB  - The recent release of the Wechsler Memory Scale Fourth Edition contains many
      improvements from a theoretical and administration perspective, including
      demographic corrections using the Advanced Clinical Solutions. Although the
      administration time has been reduced from previous versions, a shortened version
      may be desirable in certain situations given practical time limitations in
      clinical practice. The current study evaluated two- and three-subtest estimations
      of demographically corrected Immediate and Delayed Memory index scores using both
      simple arithmetic prorating and regression models. All estimated values were
      significantly associated with observed index scores. Use of Lin's Concordance
      Correlation Coefficient as a measure of agreement showed a high degree of
      precision and virtually zero bias in the models, although the regression models
      showed a stronger association than prorated models. Regression-based models
      proved to be more accurate than prorated estimates with less dispersion around
      observed values, particularly when using three subtest regression models.
      Overall, the present research shows strong support for estimating demographically
      corrected index scores on the WMS-IV in clinical practice with an adequate
      performance using arithmetically prorated models and a stronger performance using
      regression models to predict index scores.

PMID- 22376071
TI  - Condom use and prevalence of syphilis and HIV among female sex workers in Andhra
      Pradesh, India - following a large-scale HIV prevention intervention.
AB  - BACKGROUND: Avahan, the India AIDS initiative began HIV prevention interventions
      in 2003 in Andhra Pradesh (AP) among high-risk groups including female sex
      workers (FSWs), to help contain the HIV epidemic. This manuscript describes an
      assessment of this intervention using the published Avahan evaluation framework
      and assesses the coverage, outcomes and changes in STI and HIV prevalence among
      FSWs. METHODOLOGY: Multiple data sources were utilized including Avahan routine
      program monitoring data, two rounds of cross-sectional survey data (in 2006 and
      2009) and STI clinical quality monitoring assessments. Bi-variate and
      multivariate analyses, Wald Chi-square tests and multivariate logistic
      regressions were used to measure changes in behavioural and biological outcomes
      over time and their association. RESULTS: Avahan scaled up in conjunction with
      the Government program to operate in all districts in AP by March 2009. By March
      2009, 80% of the FSWs were being contacted monthly and 21% were coming to STI
      services monthly. Survey data confirmed an increase in peer educator contacts
      with the mean number increasing from 2.9 in 2006 to 5.3 in 2009. By 2008 free and
      Avahan-supported socially marketed condoms were adequate to cover the estimated
      number of commercial sex acts, at 45 condoms/FSW/month. Consistent condom use was
      reported to increase with regular (63.6% to 83.4%; AOR=2.98; p<0.001) and
      occasional clients (70.8% to 83.7%; AOR=2.20; p<0.001). The prevalence of
      lifetime syphilis decreased (10.8% to 6.1%; AOR=0.39; p<0.001) and HIV prevalence
      decreased in all districts combined (17.7% to 13.2%; AOR 0.68; p<0.01).
      Prevalence of HIV among younger FSWs (aged 18 to 20 years) decreased (17.7% to
      8.2%, p=0.008). A significant increase in condom use at last sex with occasional
      and regular clients and consistent condom use with occasional clients was
      observed among FSWs exposed to the Avahan program. There was no association
      between exposure and HIV or STIs, although numbers were small. CONCLUSIONS: The
      absence of control groups is a limitation of this study and does not allow
      attribution of changes in outcomes and declines in HIV and STI to the Avahan
      program. However, the large scale implementation, high coverage, intermediate
      outcomes and association of these outcomes to the Avahan program provide
      plausible evidence that the declines were likely associated with Avahan.
      Declining HIV prevalence among the general population in Andhra Pradesh points
      towards a combined impact of Avahan and government interventions.

PMID- 22376072
TI  - Synthesis and structure-activity relationships of new quinolone-type molecules
      against Trypanosoma brucei.
AB  - Human African trypanosomiasis (HAT) or sleeping sickness is caused by two
      subspecies of  Trypanosoma brucei ,  Trypanosoma brucei gambiense , and 
      Trypanosoma brucei rhodesiense  and is one of Africa's old plagues. It causes a
      huge number of infections and cases of death per year because, apart from limited
      access to health services, only inefficient chemotherapy is available. Since it
      was reported that quinolones such as ciprofloxacin show antitrypanosomal
      activity, a novel quinolone-type library was synthesized and tested. The
      biological evaluation illustrated that 4-quinolones with a benzylamide function
      in position 3 and cyclic or acyclic amines in position 7 exhibit high
      antitrypanosomal activity. Structure-activity relationships (SAR) are established
      to identify essential structural elements. This analysis led to lead structure
      29, which exhibits promising in vitro activity against  T. b. brucei  (IC(50) =
      47 nM) and  T. b. rhodesiense  (IC(50) = 9 nM) combined with low cytotoxicity
      against macrophages J774.1. Screening for morphological changes of trypanosomes
      treated with compounds 19 and 29 suggested differences in the morphology of
      mitochondria of treated cells compared to those of untreated cells. Segregation
      of the kinetoplast is hampered in trypanosomes treated with these compounds;
      however, topoisomerase II is probably not the main drug target.

PMID- 22376073
TI  - Evaluation of the Sexual Desire Relationship Distress Scale (SDRDS) in women with
      hypoactive sexual desire disorder.
AB  - INTRODUCTION: The Sexual Desire Relationship Distress Scale (SDRDS) was developed
      to address the need for a patient-reported outcome (PRO) measure of sexual
      distress associated with hypoactive sexual desire disorder (HSDD). The SDRDS is a
      17-item PRO that includes items related to personal distress and distress related
      to relationship with partner. AIM: The aim of this article was to evaluate the
      psychometric properties of the SDRDS among women with HSDD. METHODS: Pre- and
      post-menopausal women with HSDD or with no sexual dysfunction completed the
      SDRDS, Sexual Activity Questions, Female Sexual Distress Scale-Revised (FSDS-R),
      and desire domain of the Female Sexual Function Index (FSFI) at baseline and 2
      and 4 weeks later. MAIN OUTCOME MEASURES: The main outcome measures of this
      article were item performance, internal consistency, test-retest reliability,
      construct validity, known groups validity, and responsiveness of the SDRDS.
      RESULTS: Data from 260 women were analyzed: 101 in each of the pre- and post
      menopausal HSDD groups and 29 in each of the pre- and post-menopausal control
      groups. No differences emerged between pre- and post-menopausal women. Least
      squares mean (+/-standard errors [SE]) SDRDS score was higher in women with HSDD
      than in women with no sexual dysfunction (43.1 +/- 0.9 vs. 6.1 +/- 1.7; P <
      0.0001), supporting known groups validity. Individual item scores correlated with
      total scores (r = 0.7-0.9; P < 0.0001). Internal consistency was high, with a
      Cronbach's alpha of 0.973 at baseline. Test-retest reliability was good, with an
      intraclass correlation coefficient of 0.89. SDRDS scores correlated strongly with
      other measures of sexual distress and sexual function including the FSDS-R and
      FSFI desire domain items. Preliminary analyses suggested that the SDRDS was
      sensitive to changes in clinical status. CONCLUSIONS: The SDRDS provides a
      comprehensive and reliable assessment of distress due to decreased sexual desire
      in women with HSDD and may be a useful measure of treatment effects in clinical
      trials in women with this condition.

PMID- 22376074
TI  - Widespread atypical mitochondrial DNA structure in isopods (Crustacea,
      Peracarida) related to a constitutive heteroplasmy in terrestrial species.
AB  - Metazoan mitochondrial DNA (mtDNA) is generally composed of circular monomeric
      molecules. However, a few exceptions do exist and among them two terrestrial
      isopods  Armadillidium vulgare  and  Porcellionides pruinosus  have an atypical
      mtDNA composed of linear monomers associated with circular "head-to-head" dimers:
      a very unusual structure for animal mtDNA genome. To assess the distribution of
      this atypical mtDNA among isopods, we performed RFLP and Southern blot analyses
      on mtDNA of 16 terrestrial (Oniscidea family) and two aquatic isopod species: the
      marine  Sphaeroma serratum  (suborder Flabellifera, sister group of Oniscidea)
      and the freshwater  Asellus aquaticus  (Asellota, early derived taxon of isopod).
      The atypical mtDNA structure was observed in 15 terrestrial isopod species and A.
      aquaticus, suggesting a wide distribution of atypical mtDNA among isopods.
      However, a typical metazoan mtDNA structure was detected in the marine isopod S.
      serratum and the Oniscidea  Ligia oceanica . Our results suggest two possible
      scenarios: an early origin of the atypical mtDNA in isopods followed by reversion
      to the typical ancestral mtDNA structure for several species, or a convergent
      appearance of the atypical mtDNA structure in two isopod suborders. We compare
      this distribution of the atypical mtDNA structure with the presence of a
      heteroplasmy also observed in the mtDNA of several terrestrial isopod species. We
      discuss if this transmitted heteroplasmy is vectored by the atypical mtDNA and
      its impact on the maintenance of the atypical mtDNA in isopods.

PMID- 22376075
TI  - Association between episodes of upper respiratory infection and exacerbations in
      adult patients with asthma.
AB  - BACKGROUND: Asthma has several phenotypical features, including recurrent
      exacerbations and recurrent episodes of upper respiratory infection (URI).
      PURPOSE: A retrospective study was performed to identify the characteristics of
      adult patients with recurrent exacerbations of asthma, especially in association
      with recurrent episodes of URI. METHODS: Information was collected using a self
      administered questionnaire given to 7070 patients in autumn-winter 2006, 4859
      patients in spring-summer 2007, and 4452 patients in autumn-winter 2007. The
      patients reported the degree of symptoms and the frequency of febrile episodes of
      URI and exacerbations. Severe exacerbations were defined as a self-report of
      asthma-related hospitalization, an emergency department visit, or a requirement
      for systemic corticosteroids. Recurrent febrile URI and exacerbations were
      defined as two or more episodes within the previous 6 months. A Poisson
      regression model was used to identify the factors that were predictors of a risk
      for exacerbations. RESULTS: Of the 6266 patients who completed the questionnaire,
      the frequencies of febrile URI and episodes of severe exacerbations were 1.54 and
      0.54 per subject per year, respectively. Logistic regression analysis showed that
      an older age [odds ratio (OR): 1.57; 95% confidence interval (CI): 1.15-2.13],
      female sex (OR: 1.58; 95% CI: 1.20-2.08), recurrent febrile episodes of URI (OR:
      2.68; 95% CI: 1.47-4.91), a history of previous exacerbation within 1 year (OR:
      1.74; 95% CI: 1.28-2.34), disuse of inhaled corticosteroids (ICSs) (OR: 2.63; 95%
      CI: 1.68-4.12), and disuse of add-on leukotriene receptor antagonists (LTRAs)
      (OR: 1.42; 95% CI: 1.06-1.74) were independently associated with moderate to
      severe symptom-severity. Poisson regression analysis showed that the independent
      factors that contributed to the frequency of recurrent severe exacerbations were
      female sex (regression coefficient beta = 0.62, p < .01), an episode of sputum
      with coughing (beta = 1.23, p < .01), nocturnal awakening (beta = 1.22, p < .01),
      and severe exacerbation (beta = 0.78, p < .01) within the previous 6 months.
      CONCLUSION: Symptom-severity of asthma and the frequency of severe exacerbations
      were associated with previous exacerbations and susceptibility to URI.

PMID- 22376076
TI  - Nasal neuro EPO could be a reliable choice for neuroprotective stroke treatment.
AB  - The most common cause of stroke is cerebral ischemia, where blood flow to the
      brain is interrupted due to a thrombus in a major cerebral artery. Currently, the
      only therapeutic approach available is thrombolysis. A more recent approach that
      has started to gain attention is neuroprotection, the ability to prevent neuronal
      death and enhance endogenous protective mechanisms. Several studies have shown
      the neuroprotective action of Erythropoietin (EPO). A potential problem in the
      use of EPO for neurodegenerative disorders is the undesirable erythropoietic side
      effects. In this context, investigations have been focused to develop derivatives
      of EPO lacking erythropoietic activity but retaining neuroprotective potential.
      Low sialic acid-containing EPO (Neuro EPO) is very similar to the one that occurs
      in the mammalian brain and is rapidly degraded by the liver. Similar
      neuroprotective effects had been observed with neuro EPO, original recombinant
      human EPO and EPO variants in ischemia models. Intranasal route could be safe and
      hematological side effects could be avoided. Neuro EPO that constitutes a new
      agent has retained the neuroprotective effects without stimulating the EPOR in
      the bone marrow and can therefore be used without increasing the hematocrit. This
      review gives a brief introduction to the no hematopoietic effects of EPO, the
      evidence of neuroprotective effect, the alternatives for obtaining an EPO
      derivate without hematological side effects and discusses the advantages of nasal
      administration of Neuro EPO for neuroprotective stroke treatment.

PMID- 22376077
TI  - Metabolic stasis in an ancient symbiosis: genome-scale metabolic networks from
      two Blattabacterium cuenoti strains, primary endosymbionts of cockroaches.
AB  - BACKGROUND: Cockroaches are terrestrial insects that strikingly eliminate waste
      nitrogen as ammonia instead of uric acid. Blattabacterium cuenoti (Mercier 1906)
      strains Bge and Pam are the obligate primary endosymbionts of the cockroaches
      Blattella germanica and Periplaneta americana, respectively. The genomes of both
      bacterial endosymbionts have recently been sequenced, making possible a genome
      scale constraint-based reconstruction of their metabolic networks. The
      mathematical expression of a metabolic network and the subsequent quantitative
      studies of phenotypic features by Flux Balance Analysis (FBA) represent an
      efficient functional approach to these uncultivable bacteria. RESULTS: We report
      the metabolic models of Blattabacterium strains Bge (iCG238) and Pam (iCG230),
      comprising 296 and 289 biochemical reactions, associated with 238 and 230 genes,
      and 364 and 358 metabolites, respectively. Both models reflect both the striking
      similarities and the singularities of these microorganisms. FBA was used to
      analyze the properties, potential and limits of the models, assuming some
      environmental constraints such as aerobic conditions and the net production of
      ammonia from these bacterial systems, as has been experimentally observed. In
      addition, in silico simulations with the iCG238 model have enabled a set of
      carbon and nitrogen sources to be defined, which would also support a viable
      phenotype in terms of biomass production in the strain Pam, which lacks the first
      three steps of the tricarboxylic acid cycle. FBA reveals a metabolic condition
      that renders these enzymatic steps dispensable, thus offering a possible
      evolutionary explanation for their elimination. We also confirm, by computational
      simulations, the fragility of the metabolic networks and their host dependence.
      CONCLUSIONS: The minimized Blattabacterium metabolic networks are surprisingly
      similar in strains Bge and Pam, after 140 million years of evolution of these
      endosymbionts in separate cockroach lineages. FBA performed on the reconstructed
      networks from the two bacteria helps to refine the functional analysis of the
      genomes enabling us to postulate how slightly different host metabolic contexts
      drove their parallel evolution.

PMID- 22376078
TI  - Population pharmacokinetic model of canrenone after intravenous administration of
      potassium canrenoate to paediatric patients.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Little is known about the
      pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT
      THIS STUDY ADDS: A population pharmacokinetic model has been developed to
      evaluate the pharmacokinetics of canrenone in paediatric patients who received
      potassium canrenoate as part of their therapy in the intensive care unit. AIMS To
      characterize the population pharmacokinetics of canrenone following
      administration of potassium canrenoate to paediatric patients. METHODS: Data were
      collected prospectively from 23 paediatric patients (2 days to 10 years of age;
      median weight 4 kg, range 2.16-28.0 kg) who received intravenous potassium
      canrenoate (K-canrenoate) as part of their intensive care therapy for removal of
      retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the
      management of congestive heart failure. Plasma samples were analyzed by HPLC for
      determination of canrenone (the major metabolite and pharmacologically active
      moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS:
      A one compartment model best described the data. The only significant covariate
      was weight (WT). The final population models for canrenone clearance (CL/F) and
      volume of distribution (V/F) were CL/F (l h(-1) ) = 11.4 * (WT/70.0)(0.75) and
      V/F (l) = 374.2 * (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg
      child would be 1.33 l h(-1) and 21.4 l, respectively, resulting in an elimination
      half-life of 11.2 h. CONCLUSIONS: The range of estimated CL/F in the study
      population was 0.67-7.38 l h(-1) . The data suggest that adjustment of K
      canrenoate dosage according to body weight is appropriate in paediatric patients.

PMID- 22376080
TI  - Treatment of multifocal pain with spinal cord stimulation.
AB  - INTRODUCTION: We report a retrospective case study of combined treatment of
      cancer-related pain and chronic low back and lower extremity pain related to
      postlaminectomy syndrome (PLS) with one spinal cord stimulation (SCS) system.
      METHODS: The patient underwent an uneventful SCS trial with percutaneous
      placement of two temporary eight-electrode leads (Medtronic Inc., Minneapolis,
      MN) placed at the level of T8-T9-T10 and T5-T6-T7. RESULTS: After successful
      trial, he was implanted with permanent leads and generator, reporting sustained
      pain relief at 12-month follow-up visit. DISCUSSION: SCS is a trialable,
      reversible, and interactive therapy permitting patients to control the level of
      stimulation they feel based on their degree of pain. CONCLUSION: SCS provides an
      effective, alternative treatment for select patients with cancer-related chest
      wall pain and pain related to PLS who have failed conservative treatment.

PMID- 22376079
TI  - ERK/pERK expression and B-raf mutations in colon adenocarcinomas: correlation
      with clinicopathological characteristics.
AB  - BACKGROUND: Colorectal (CRC) carcinogenesis through various morphological stages
      has been linked to several genetic and epigenetic changes. The Raf/MEK/ERK (MAPK)
      signal transduction cascade is an important mediator of a number of cellular
      fates. METHODS: In this study, we investigated the presence of B-raf and K-ras
      mutations in 94 consecutive cases of primary colon adenocarcinoma in correlation
      with the immunohistochemical expression of total and activated ERK and the
      expression of mismatch repair proteins (MMR) hMLH1 and hMSH2 as well as their
      correlations with standard clinicopathological parameters. RESULTS: The
      immunostaining pattern for total and activated ERK was nuclear and cytoplasmic.
      hMLH1 and hMSH2 proteins were preserved in 45/63 (71.43%) cases and 35/53
      (66.04%) cases respectively. Total ERK nuclear expression, was positively
      correlated with tumor stage (p = 0.049), whereas nuclear pERK expression was
      positively correlated with histological grade (p = 0.0113) and tumor stage (p =
      0.0952), although the latter relationship was of marginal significance. DNA
      sequencing showed that 12 samples (12.7%) had a mutation in B-RAF Exon 15 and
      none in Exon 11, whereas 22 (23.4%) had a K-ras mutation. Disruption of the MAP
      kinase pathway-either through K-ras or B-raf mutation-was detected in 37% of all
      the examined cases, although the overexpression of total and activated ERK1/2 was
      not correlated with the mutational status of K-ras or B-raf genes. Finally, the
      preservation of hMLH1 or hMSH2 immunoexpression was not correlated with the
      presence of B-raf and/or K-ras mutations. CONCLUSIONS: In this study, we present
      evidence that ERK activation occurs in a K-ras or B-raf -independent manner in
      the majority of primary colon cancer cases. Moreover, B-raf mutations are not
      associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2
      expression. Activated ERK could possibly be implicated in tumor invasiveness as
      well as in the acquisition of a more aggressive phenotype.

PMID- 22376081
TI  - Higher morning to evening ratio in total dose of twice-daily biphasic insulin
      analog might be effective in achieving glucose control in patients with poorly
      controlled type 2 diabetes.
AB  - BACKGROUND: The aims of this study are to investigate not only the glucose
      lowering effectiveness of twice-daily premixed insulin lispro 25 (Humalog((r))
      Mix25(TM), Eli Lilly and Co., Indianapolis, IN), but also the optimal divided
      ratio of total Mix25 dose in Korean patients with poorly controlled type 2
      diabetes. SUBJECTS AND METHODS: In this retrospective study, we retrieved data
      for subjects who were on intensive insulin therapy with twice-daily Mix25 regimen
      for at least 24 weeks. Changes of hemoglobin A1c (HbA(1c)) and other clinical and
      laboratory parameters were evaluated. Two groups were defined according to dose
      ratio of pre-breakfast to pre-dinner insulin at 24 weeks: Group I, pre
      breakfast:pre-dinner insulin dose ratio=50:50; Group II, ratio=53:47-75:25.
      RESULTS: In total, 143 subjects were ultimately analyzed in this study. Twice
      daily Mix25 significantly improved HbA(1c) levels from 10.1% to 7.7%, and 34% of
      patients had reached the target glycemic goal (HbA(1c)<7%) after 24 weeks.
      Compared with Group I, a significant reduction in HbA(1c) (Group I vs. Group II, 
      1.9+/-0.3% vs. -2.8+/-0.3%, P=0.02) and a larger proportion of subjects with
      HbA(1c)<7% (23.2% vs. 46.7%, P=0.01) were observed in subjects in Group II. Among
      clinical and laboratory factors, duration of diabetes (odd ratios [OR]=0.93, 95%
      confidence interval [CI] 0.86-0.99, P=0.04) and history of sulfonylurea use
      (OR=0.27, 95% CI 0.10-0.72, P=0.01) were independently associated with achieving
      target HbA(1c) levels less than 7%. CONCLUSIONS: Twice-daily Mix25 is an
      effective option for Korean subjects with type 2 diabetes having uncontrolled
      hyperglycemia. A higher pre-breakfast/pre-dinner dose ratio (53:47-75:25) might
      be taken into consideration as an initial protocol to accomplish better glycemic
      control in twice-daily Mix25.

PMID- 22376082
TI  - Correlation between sweat glucose and blood glucose in subjects with diabetes.
AB  - BACKGROUND: Sweat contains glucose that can accurately reflect blood glucose.
      However, skin surface glucose can confound these measurements. METHODS: A
      perfusion method was used to rapidly harvest sweat from forearm sites on human
      subjects. The sweat samples were analyzed for glucose by high-performance liquid
      chromatography methods and compared with the results obtained with a blood
      glucose meter. RESULTS: The results of 23 different studies of seven individual
      subjects with diabetes show a strong correlation between sweat glucose and blood
      glucose. CONCLUSION: Sweat glucose, when properly harvested to prevent
      contamination from other sources on the skin's surface, can accurately reflect
      blood glucose levels.

PMID- 22376083
TI  - Prevention is the key to maintaining gynecologic health during deployment.
AB  - Researchers have indicated that since Operation Desert Storm, the majority of
      gynecologic problems exhibited during deployment are from vaginal and urinary
      tract infections and menstrual disorders. The purpose of this article is to
      provide an overview of military women's health issues during military operations
      and summarize current knowledge and recommendations to promote their gynecologic
      health needs while deployed. Military women would benefit from predeployment
      health-promotion programs that focus on preventive measures to enhance
      gynecologic health while deployed.

PMID- 22376084
TI  - Control of Xiphinema index populations by fallow plants under greenhouse and
      field conditions.
AB  - The dagger nematode Xiphinema index has a high economic impact in vineyards by
      direct pathogenicity and above all by transmitting the Grapevine fanleaf virus
      (GFLV). Agrochemicals have been largely employed to restrict the spread of GFLV
      by reducing X. index populations but are now banned. As an alternative to
      nematicides, the use of fallow plants between two successive vine crops was
      assessed. We selected plant species adapted to vineyard soils and exhibiting
      negative impact on nematodes and we evaluated their antagonistic effect on X.
      index in greenhouse using artificially infested soil, and in naturally infested
      vineyard conditions. The screening was conducted with plants belonging to the
      families Asteraceae (sunflower, marigold, zinnia, and nyjer), Poaceae (sorghum
      and rye), Fabaceae (white lupin, white melilot, hairy vetch, and alfalfa),
      Brassicaceae (rapeseed and camelina), and Boraginaceae (phacelia). In the
      greenhouse controlled assay, white lupin, nyjer, and marigold significantly
      reduced X. index populations compared with that of bare soil. The vineyard assay,
      designed to take into account the aggregative pattern of X. index distribution,
      revealed that marigold and hairy vetch are good candidates as cover crops to
      reduce X. index populations in vineyard. Moreover, this original experimental
      design could be applied to manage other soilborne pathogens.

PMID- 22376085
TI  - State-of-the art comparability of corrected emission spectra. 1. Spectral
      correction with physical transfer standards and spectral fluorescence standards
      by expert laboratories.
AB  - The development of fluorescence applications in the life and material sciences
      has proceeded largely without sufficient concern for the measurement
      uncertainties related to the characterization of fluorescence instruments. In
      this first part of a two-part series on the state-of-the-art comparability of
      corrected emission spectra, four National Metrology Institutes active in high
      precision steady-state fluorometry performed a first comparison of fluorescence
      measurement capabilities by evaluating physical transfer standard (PTS)-based and
      reference material (RM)-based calibration methods. To identify achievable
      comparability and sources of error in instrument calibration, the emission
      spectra of three test dyes in the wavelength region from 300 to 770 nm were
      corrected and compared using both calibration methods. The results, obtained for
      typical spectrofluorometric (0 degrees /90 degrees  transmitting) and
      colorimetric (45 degrees /0 degrees  front-face) measurement geometries,
      demonstrated a comparability of corrected emission spectra within a relative
      standard uncertainty of 4.2% for PTS- and 2.4% for RM-based spectral correction
      when measurements and calibrations were performed under identical conditions.
      Moreover, the emission spectra of RMs F001 to F005, certified by BAM, Federal
      Institute for Materials Research and Testing, were confirmed. These RMs were
      subsequently used for the assessment of the comparability of RM-based corrected
      emission spectra of field laboratories using common commercial
      spectrofluorometers and routine measurement conditions in part 2 of this series
      (subsequent paper in this issue).

PMID- 22376086
TI  - Structural insight into iodide uptake by AFm phases.
AB  - The ability of cement phases carrying positively charged surfaces to retard the
      mobility of (129)I, present as iodide (I(-)) in groundwater, was investigated in
      the context of safe disposal of radioactive waste. (125)I sorption experiments on
      ettringite, hydrotalcite, chloride-, carbonate- and sulfate-containing AFm phases
      indicated that calcium-monosulfate (AFm-SO(4)) is the only phase that takes up
      trace levels of iodide. The structures of AFm phases prepared by coprecipitating
      iodide with other anions were investigated in order to understand this
      preferential uptake mechanism. X-ray diffraction (XRD) investigations showed a
      segregation of monoiodide (AFm-I(2)) and Friedel's salt (AFm-Cl(2)) for I-Cl
      mixtures, whereas interstratifications of AFm-I(2) and hemicarboaluminate (AFm-OH
      (CO(3))(0.5)) were observed for the I-CO(3) systems. In contrast, XRD
      measurements indicated the formation of a solid solution between AFm-I(2) and AFm
      SO(4) for the I-SO(4) mixtures. Extended X-ray absorption fine structure
      spectroscopy showed a modification of the coordination environment of iodine in I
      CO(3) and in I-SO(4) samples compared to pure AFm-I(2). This is assumed to be due
      to the introduction of stacking faults in I-CO(3) samples on one hand and due to
      the presence of sulfate and associated space-filling water molecules as close
      neighbors in I-SO(4) samples on the other hand. The formation of a solid solution
      between AFm-I(2) and AFm-SO(4), with a short-range mixing of iodide and sulfate,
      implies that AFm-SO(4) bears the potential to retard (129)I.

PMID- 22376087
TI  - Interaction of alpha-synuclein and a cell penetrating fusion peptide with higher
      eukaryotic cell membranes assessed by 19F NMR.
AB  - We show that fluorine NMR can be used to monitor the insertion and change in
      conformation of a 19F-labeled cell-penetrating peptide upon interacting with the
      cellular plasma membrane. alpha-Synuclein and a construct comprising a cell
      penetrating peptide covalently attached to its N-terminus were studied. Important
      information about the interaction of the proteins with CHO-K1 cells was obtained
      by monitoring the diminution of 19F resonances of 3-fluoro-l-tyrosine labeled
      proteins. For alpha-synuclein, a decrease in the resonance from position 39 was
      observed indicating that only the N-terminal third region of the protein
      interacts with plasma membrane. However, when the fusion construct was incubated
      with the cells, a decrease in the resonance from the fusion peptide region was
      noted with no change in the resonances from alpha-synuclein region. Longer
      incubation, studied by using confocal fluorescence microscopy, revealed that the
      fusion construct translocates into the cells, but alpha-synuclein alone did not
      cross the membrane in significant amounts.

PMID- 22376088
TI  - The effect of short time periods of pre-operative warming in the prevention of
      peri-operative hypothermia.
AB  - The aim of our study was to evaluate the performance of different durations of
      active pre-operative skin-surface warming (pre-warming) to prevent peri-operative
      hypothermia and postoperative shivering. We randomly assigned 200 patients,
      scheduled for surgery of 30-90 min under general anaesthesia, to receive passive
      insulation or forced-air skin surface warming for 10, 20 or 30 min. Body
      temperature was measured at the tympanic membrane. Shivering was graded by visual
      inspection. There were significant differences in changes of core temperature
      between the non-pre-warmed group and all the pre-warmed groups (p < 0.00001), but
      none between the three pre-warmed groups (p = 0.54). Without pre-warming, 38/55
      (69%) patients became hypothermic (< 36  degrees C) at the end of anaesthesia,
      whereas only 7/52 (13%), 3/43 (7%) and 3/50 (6%) patients following 10, 20 or 30
      min pre-warming, respectively, became hypothermic (p < 0.001 vs no pre-warming).
      Shivering was observed in 10 patients without, and in three, three and one
      patients with pre-warming in the respective groups (p = 0.02). Pre-warming of
      patients for only 10 or 20 min before general anaesthesia mostly prevents
      hypothermia and reduces shivering.

PMID- 22376090
TI  - Special issue: Dentomaxillofacial radiology: an update and the latest on cone
      beam imaging. An Australian Dental Journal special supplement.

PMID- 22376091
TI  - Update on the biological effects of ionizing radiation, relative dose factors and
      radiation hygiene.
AB  - Diagnostic imaging is an indispensable part of contemporary medical and dental
      practice. Over the last few decades there has been a dramatic increase in the use
      of ionizing radiation for diagnostic imaging. The carcinogenic effects of high
      dose exposure are well known. Does diagnostic radiation rarely cause cancer? We
      don't know but we should act as if it does. Accordingly, dentists should select
      patients wisely - only make radiographs when there is patient-specific reason to
      believe there is a reasonable expectation the radiograph will offer unique
      information influencing diagnosis or treatment. Low-dose examinations should be
      made: intraoral imaging - use fast film or digital sensors, thyroid collars,
      rectangular collimation; panoramic and lateral cephalometric imaging - use
      digital systems or rare-earth film screen combinations; and cone beam computed
      tomography - use low-dose machines, restrict field size to region of interest,
      reduce mA and length of exposure arc as appropriate.

PMID- 22376092
TI  - Contemporary medico-legal dental radiology.
AB  - The advent of extraoral radiology in general dental practice has become more
      widespread since 2000, particularly with digital systems. With this comes a range
      of medico-legal risks for dentists not adverted to previously. These risks
      include a higher than expected radiation dose for some surveys, and the risk of a
      'loss of a chance' for a patient whereby the images may disclose pathology not
      diagnosed by general dental practitioners using OPG and CBVT radiology.
      Practitioners need to apply relevant legal principles in deciding which surveys
      to order and record, and also need to explain to patients the dosages of the
      radiation that they will likely receive. Practitioners also need to assess
      whether the resultant survey ought to be interpreted by a radiologist to diagnose
      any wider pathology with which a general practitioner may not be familiar. Extra
      caution needs to be used in ordering high dose radiology in paediatric patients.
      Dentists should not assume patients fully understand the nature of CBVT and MCT,
      and its risks and benefits. Consideration ought to be given to the volume of CBVT
      ordered dependent on factors such as patient age, symptoms, history and
      procedural intent.

PMID- 22376093
TI  - The impact of computer display performance on the quality of digital radiographs:
      a review.
AB  - Radiography makes an essential contribution to the processes of examination,
      diagnosis and treatment planning in dentistry. While the use of film-based
      imaging still predominates in dentistry, digital imaging is gaining wider
      acceptance and the use of this modality is anticipated to expand in the future.
      Two concerns associated with this transition have been raised in the literature.
      The first of these is the dissatisfaction experienced by many dental
      professionals with quality of digital radiographs when compared to plain film. In
      addition, there are indications that practitioners feel limited in their
      understanding of those factors impacting on digital image quality. One key area
      highlighted in the literature as having a significant influence on digital
      radiographic quality and interpretation concerns the performance of the display
      device. Within the last decade, research derived from the fields of medical
      radiology and physics have demonstrated that suboptimally performing displays
      degrade image quality, thereby increasing the potential for compromised
      diagnostic outcomes. In the field of medicine, this has resulted in the
      establishment of standards applicable to computer displays used in diagnostic
      radiology. Conversely, limited guidelines exist in the field of dentistry. The
      aim of this review is to provide an outline of these standards and highlight the
      important relationship between computer display performance and digital image
      quality.

PMID- 22376094
TI  - Collection and recording of radiological information for forensic purposes.
AB  - Forensic odontology is the application of dental expertise to legal issues.
      Commonly, it involves the comparison of dental records of a missing person with a
      deceased individual for the purposes of forensic personal identification, either
      in a single case, or as part of the response to an event involving multiple
      simultaneous fatalities (Disaster Victim Identification, or DVI). It may also
      involve studies to determine the age of an individual, which may be required as
      part of a forensic identification process, or for another legal purpose such as
      the determination of legal responsibility, or in connection with immigration.
      This report examines the types of radiological information currently used in such
      forensic studies, and discusses how this information may be accessed or recorded,
      as well as the techniques that are commonly applied to the radiological data to
      reach a satisfactory outcome for application in forensic casework.

PMID- 22376095
TI  - The basic principles of radiological interpretation.
AB  - Radiologic interpretation is a complex process which involves the application of
      an appropriate algorithm in the study of radiologic images and the ability to
      understand the meaning and to weight the various findings, ultimately
      contributing to diagnosis. Prerequisites include the knowledge of orofacial
      radiologic anatomy and the various pathoses which may arise or manifest in this
      region of the body. An understanding of the strengths and limitations of the
      modality employed is also essential. The process of interrogating radiologic
      images for abnormalities varies, depending on the modality. This paper outlines
      the basic steps involved in the radiologic examination of abnormalities which
      affect the jaws, primarily in relation to plain 2-D imaging.

PMID- 22376096
TI  - Interpretation of panoramic radiographs.
AB  - Panoramic radiography has become a commonly used imaging modality in dental
      practice and can be a valuable diagnostic tool in the dentist's armamentarium.
      However, the panoramic image is a complex projection of the jaws with multiple
      superimpositions and distortions which may be exacerbated by technical errors in
      image acquisition. Furthermore, the panoramic radiograph depicts numerous
      anatomic structures outside of the jaws which may create additional
      interpretation challenges. Successful interpretation of panoramic radiographs
      begins with an understanding of the normal anatomy of the head and neck and how
      it is depicted in this image type. This article will describe how osseous
      structures, soft tissues, air spaces and ghost shadows contribute to the final
      panoramic image. A systematic and repeated approach to examining panoramic
      radiographs, which is recommended to ensure that critical findings are not
      overlooked, is also outlined. Examples of challenging interpretations, including
      variations of anatomy, artefacts and disease, are presented to illustrate these
      concepts.

PMID- 22376097
TI  - Maxillofacial cone beam computed tomography: essence, elements and steps to
      interpretation.
AB  - Maxillofacial cone beam computed tomography (CBCT) is one of the most significant
      advances in dental imaging since rotational panoramic radiography. While the
      acquisition of CBCT data is technically simple, numerous parameters should be
      considered so that CBCT imaging is performed appropriately and 'task specific'.
      This involves an understanding of not only exposure (e.g. geometric and software
      parameters to minimize patient dose, while sustaining diagnostic image quality)
      but also image formatting options to maximize image display. CBCT images contain
      far more detailed information of the maxillofacial region than do panoramic or
      other 2-D images and necessitate a thorough knowledge of the 3-D anatomy of the
      region and considerations of variability in the range of the anatomically normal.
      These principles, procedures and protocols, together with the interpretation of
      CBCT images form the basis of best practices in maxillofacial CBCT imaging. This
      communication aims to provide: (1) an overview of the fundamental principles of
      operation of maxillofacial CBCT technology; (2) an understanding of 'task
      specific' equipment, image selection and image display modes; and (3) a
      systematic methodology for sequencing interpretation of CBCT images.

PMID- 22376098
TI  - Cone beam computed tomography and obstructive sleep apnoea.
AB  - Sleep apnoea is characterized by an intermittent cessation or diminution of
      airflow during sleep that may result in significant pulmonary and cardiac
      consequences, and is associated with significant morbidity and mortality. It is a
      common disease that affects approximately 20% of patients who snore, equating to
      a total prevalence in the population of about 4% of all middle aged men and 2% of
      women. In reality, due to lack of recognition and the difficulty with obtaining
      an accurate diagnosis, the actual incidence is likely much higher.

PMID- 22376099
TI  - Application of cone beam volumetric tomography in endodontics.
AB  - In a 2008 article on cone beam volumetric tomography (CBVT) and dentoalveolar
      applications, Tyndall and Rathore wrote: 'It is in the area of endodontic
      applications that the literature has proved most fruitful to date.' This
      statement is even truer today than in 2008. A review of the literature has
      demonstrated that, in many cases, CBVT is more efficacious than traditional forms
      of 2-D imaging. Endodontic applications of CBVT include the diagnosis of
      periapical lesions due to pulpal inflammation, identification and localization of
      internal and external resorption, the detection of vertical root fractures, the
      visualization of accessory canals, and elucidation of the causes of non-healing
      endodontically treated teeth. Prior to 2008, most published articles on CBVT
      applications in endodontics were either case reports or in vitro studies. Since
      that time more well designed clinically related scholarly activity has been
      published. This article attempts to survey the field of CBVT applications in
      endodontics and provide the readers with an overview of what has been found. The
      authors hope that this knowledge will form a foundation for appropriate clinical
      decision making with specific reference to selection criteria for the endodontic
      applications of CBVT.

PMID- 22376100
TI  - Application of cone beam computed tomography in oral and maxillofacial surgery.
AB  - In the past decade, the utility of cone beam computed tomography (CBCT) images in
      oral and maxillofacial surgery has seen continuous increase. However, CBCT images
      are not always able to replace other imaging modalities. Based on the current
      published knowledge, this paper discusses advantages and limitations of CBCT
      images in the diagnosis and surgical planning of dentoalveolar procedures,
      odontogenic cysts, benign and malignant tumours, inflammatory changes,
      orthognathic surgery, maxillofacial trauma, sinus disorders, and systemic and
      osseous conditions that manifest in the maxillofacial area. This paper also
      suggests alternative imaging modalities when CBCT images are not adequate for
      surgical planning.

PMID- 22376101
TI  - Cone beam computed tomography use in orthodontics.
AB  - Cone beam computed tomography (CBCT) is widely used by orthodontists to obtain
      three-dimensional (3-D) images of their patients. This is of value as
      malocclusion results from discrepancies in three planes of space. This review
      tracks the use of CBCT in orthodontics, from its validation as an accurate and
      reliable tool, to its use in diagnosing and treatment planning, and in assessing
      treatment outcomes in orthodontics.

PMID- 22376102
TI  - Is there a role for the use of volumetric cone beam computed tomography in
      periodontics?
AB  - Volumetric computed cone beam tomography offers a number of significant
      advantages over conventional intraoral and extraoral panoramic radiography, as
      well as computed tomography. To date, periodontal diagnosis has relied heavily on
      the assessment of both intraoral radiographs and extraoral panoramic radiographs.
      With emerging technology in radiology there has been considerable interest in the
      role that volumetric cone beam computed tomography might play in periodontal
      diagnostics. This narrative reviews the current evidence and considers whether
      there is a role for volumetric cone beam computed tomography in periodontics.

PMID- 22376103
TI  - Application of cone beam computed tomography for assessment of the
      temporomandibular joints.
AB  - Radiographic examination is essential for the diagnosis and management of
      temporomandibular joint (TMJ) disorders. The goals of TMJ radiography are to
      evaluate cortical and trabecular architecture of the bony structures and confirm
      their integrity, to assess the extent and monitor progression of osseous changes,
      and to evaluate the response to treatment. Accurate evaluation of the TMJ by
      conventional radiography is limited by structure superimposition. Cone beam
      computed tomography (CBCT) provides high-resolution multiplanar images and
      delivers substantially lower radiation dose, compared with multislice CT. CBCT
      allows examination of TMJ anatomy without superimposition and distortion to
      facilitate analysis of bone morphology, joint space and dynamic function in all
      three dimensions. This article will describe the role of CBCT imaging for the
      assessment of the TMJ osseous structures and present typical appearances of
      common pathological conditions of the TMJ.

PMID- 22376104
TI  - State-of-the-art methodologies for the discovery and characterization of DNA G
      quadruplex binders.
AB  - Nowadays, the molecular basis of interaction between low molecular weight
      compounds and biological macromolecules is the subject of numerous investigations
      aimed at the rational design of molecules with specific therapeutic applications.
      In the last decades, it has been demonstrated that DNA quadruplexes play a
      critical role in several biological processes both at telomeric and gene
      promoting levels thus providing a great stride in the discovery of ligands able
      to interact with such a biologically relevant DNA conformation. So far, a number
      of experimental and computational approaches have been successfully employed in
      order to identify new ligands and to characterize their binding to the DNA. The
      main focus of this review is the description of these methodologies, placing a
      particular emphasis on computational methods, isothermal titration calorimetry
      (ITC), mass spectrometry (MS), nuclear magnetic resonance (NMR), circular
      dichroism (CD) and fluorescence spectroscopies.

PMID- 22376105
TI  - Recent developments in the chemistry and biology of G-quadruplexes with reference
      to the DNA groove binders.
AB  - DNA is the chemotherapeutic target for treating diseases of genetic origin.
      Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA
      etc.), DNA is capable of forming several multi-stranded structures (triplex,
      tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3'
      ends of chromosomes, called telomeres, are synthesized by telomerase, a
      ribonucleoprotein, and over-expression of telomerase is associated with cancer.
      The activity of telomerase is suppressed if the G-rich region is folded into the
      four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic
      ligands. Thus design and synthesis of new G4- DNA ligands is an attractive
      strategy to combat cancer. G4-DNA forming sequences are also prevalent in other
      genomic regions of biological significance including promoter regions of several
      oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA
      structure within the G-rich promoter sequences. To date, several G4-DNA
      stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA
      through the grooves (major and minor groove) in a sequence-specific manner. Some
      of the groove binders are known to stabilize the G4-DNA. However, this is a
      relatively under explored field of research. In this review, we focus on the
      recent advances in the understanding of the G4-DNA structures, particularly made
      from the human telomeric DNA stretches. We summarize the results of various
      investigations of the interaction of various organic ligands with the G4-DNA
      while highlighting the importance of groove binder-G4-DNA interactions.

PMID- 22376106
TI  - Structure conversion and structure separation of G-quadruplexes investigated by
      carbazole derivatives.
AB  - The challenge of G-quadruplexes is that the G-rich sequences can adopt various G4
      structures and possibly interconvert among them, particularly under the change of
      environmental conditions. Both NMR and circular dichroism (CD) show the spectral
      conversion of d[AG3(T2AG3)3] (HT22) from Na-form to K-form after Na+/K+ ion
      exchange. No appreciable change on the induced CD spectra of BMVC molecule and
      the single molecule tethered particle motion of HT22 in Na+ solution upon K+
      titration suggests that the spectral conversion is unlikely due to the structural
      conversion via fully unfolded intermediate. Although a number of mechanisms were
      proposed for the spectral change induced by the Na+/K+ ion exchange, determining
      the precise structures of HT22 in K+ solution may be essential to unravel the
      mechanism of the structural conversion. Thus, development of a new method for
      separating different structures is of critical importance for further individual
      verification. In the second part of this review, we describe a new approach based
      on "micelle-enhanced ultrafiltration" method for DNA structural separation. The
      BMVC, a G-quadruplex ligand, is first modified and then forms a large size of
      emulsion after ultrasonic emulsification, together with its different binding
      affinities to various DNA structures; for the first time, we are able to separate
      different DNA structures after membrane filtration. Verification of the possible
      structural conversion and investigation of structural diversity among various G4
      structures are essential for exploring their potential biological roles and for
      developing new anticancer drugs.

PMID- 22376107
TI  - Thrombin binding aptamer, more than a simple aptamer: chemically modified
      derivatives and biomedical applications.
AB  - The thrombin binding aptamer (TBA) is a well characterized chair-like,
      antiparallel quadruplex structure that binds specifically to thrombin at
      nanomolar concentrations and therefore it has interesting anticoagulant
      properties. In this article we review the research involved in the development of
      new TBA derivatives with improved anticoagulant properties as well as the use of
      the TBA as a model compound for the study of quadruplex structures. Specifically,
      we describe the impact of modified nucleosides and non-natural backbones in the
      guanine tetrads or in the loops and the introduction of pendant groups at the 3'
      or 5'-ends. The modified oligonucleotides are shown to be excellent tools for the
      understanding of the molecular structure of the TBA and its folding properties.
      Finally, we review the use of the TBA-Thrombin recognition system for the
      development of analytical tools based on the TBA folding.

PMID- 22376108
TI  - Experimental methods for studying the interactions between G-quadruplex
      structures and ligands.
AB  - The present paper reviews the recent advances in and applications of experimental
      techniques used to study interactions between G-quadruplex structures and ligands
      that are potentially of pharmaceutical interest. Several instrumental techniques
      are used to study such interactions. The application of spectroscopic techniques
      such as molecular absorption, circular dichroism, molecular fluorescence, mass
      spectrometry and nuclear magnetic resonance are reviewed and we discuss the type
      of information (qualitative or quantitative) that can be obtained from the use of
      each technique. Additionally, the application of complementary techniques such as
      surface plasmon resonance, isothermal titration calorimetry and different methods
      based on biochemistry is considered. For each technique, the main applications
      are presented and they are classified according to the family of the ligand and
      the type of G-quadruplex forming sequence (human telomeric or promoter region of
      oncogenes) considered.

PMID- 22376109
TI  - Cell cycle regulation of G-quadruplex DNA structures at telomeres.
AB  - DNA and RNA regions containing tracts of guanines can form very stable secondary
      structures called G-quadruplex (G4). Genomic sequences with the potential to form
      G4 (G4-motifs) are abundant across species. In all analyzed genomes G4 motifs are
      found near promoter regions and double strand break sites and at telomeres.
      Telomeres are very G-rich and prone for G4 formation. Therefore they are
      routinely used in in vitro and in vivo experiments to elucidate the function of
      G4 structures in telomere metabolism. Recently various labs demonstrated that
      telomere length maintenance is mediated via G4 structures. Telomere-binding
      proteins specifically bind to G4 structure and regulate this structure throughout
      the cell cycle.

PMID- 22376110
TI  - Luminescent G-quadruplex probes.
AB  - G-quadruplexes have found increasing potential in applications such as molecular
      therapeutics, diagnostics, and sensing. As a consequence, small molecules capable
      of selectively detecting G-quadruplexes have received significant attention in
      recent literature. Our review here addresses representative advances in the
      development of luminescent G-quadruplex probes and highlights their potential
      applications in sensing and imaging.

PMID- 22376111
TI  - RNA G-quadruplexes: G-quadruplexes with "U" turns.
AB  - G-quadruplexes are non canonical secondary structures held together by Hoogsteen
      bonded planar guanine quartets formed in G-rich sequences in DNA and RNA.
      Considerable research over the past three decades has contributed to a great deal
      of understanding of these unusual structures in DNA. Various factors governing
      the stability of DNA quadruplexes coupled with their in vivo existence have been
      well documented. RNA has emerged as a key regulatory player in the functioning of
      the cell shifting the focus to RNA G-quadruplexes which were discovered recently.
      RNA G-quadruplexes demonstrate immense potential for in vivo existence and
      function due to their inherent chemistry. We have highlighted the major findings
      of the field and compared them to structural aspects of DNA quadruplexes.
      Further, the plausible functions of RNA G-quadruplexes such as translational
      suppression, splicing etc. are discussed in brief, suggesting scope for an
      extensive role of these structures in biological systems. As the field is
      growing, we endeavor to review the current knowledge and evaluate the various
      attributes of RNA G- quadruplex structure, stability, function and applications.
      We have also attempted to evaluate the physical and physiological role and
      relevance of these motifs.

PMID- 22376113
TI  - G-quadruplex binding ligands: from naturally occurring to rationally designed
      molecules.
AB  - Guanine-rich nucleic acid sequences are known to form G-quadruplex - four
      stranded DNA or RNA structures stabilized by an array of Hoogsteen hydrogen
      bonds. G-quadruplex structures are involved in the modulation of gene expression
      at the transcription and translation levels. Accordingly, G-quadruplexes are
      considered as novel therapeutic targets for anticancer drug development. In this
      review, the authors provide a brief, up-to-date summary of G-quadruplex binding
      ligands, including naturally occurring molecules, synthetic compounds, and
      molecules identified by computational database screening. The key structural
      motifs of G-quadruplex binding ligands, that is, an aromatic core and basic side
      chains, are addressed in the context of how these molecules interact with G
      quadruplex. A better understanding of these interactions would facilitate the
      rational design of ligands selective for DNA or RNA G-quadruplex.

PMID- 22376112
TI  - Targeting DNA G-quadruplex structures with peptide nucleic acids.
AB  - Regulation of genetic functions based on targeting DNA or RNA sequences with
      complementary oligonucleotides is especially attractive in the post-genome era.
      Oligonucleotides can be rationally designed to bind their targets based on simple
      nucleic acid base pairing rules. However, the use of natural DNA and RNA
      oligonucleotides as targeting probes can cause numerous off-target effects. In
      addition, natural nucleic acids are prone to degradation in vivo by various
      nucleases. To address these problems, nucleic acid mimics such as peptide nucleic
      acids (PNA) have been developed. They are more stable, show less off-target
      effects, and, in general, have better binding affinity to their targets. However,
      their high affinity to DNA can reduce their sequence-specificity. The formation
      of alternative DNA secondary structures, such as the G-quadruplex, provides an
      extra level of specificity as targets for PNA oligomers. PNA probes can target
      the loops of G-quadruplex, invade the core by forming PNA-DNA guanine-tetrads, or
      bind to the open bases on the complementary cytosine-rich strand. Not only could
      the development of such G-quadruplex-specific probes allow regulation of gene
      expression, but it will also provide a means to clarify the biological roles G
      quadruplex structures may possess.

PMID- 22376114
TI  - Folding versus charge: understanding selective target recognition by the thrombin
      aptamers.
AB  - The use of nucleic acids as drugs represents a consistently growing approach.
      Different therapeutical strategies take advantage of the biological and
      biophysical properties of DNA and RNA to properly modulate activity of selected
      targets. A peculiar characteristic of these molecules is their structural
      flexibility which allows them to assume distinct foldings depending upon their
      sequence and/or environment. During the last twenty years this has led to the
      theoretical and experimental development of oligonucleotide aptamers, short
      sequences which can recognize a target with specificity and affinity comparable
      to antibodies. A leading example is represented by the Thrombin aptamer (15fTBA),
      a 15-mer DNA selected by its high affinity for the exosite I (fibrinogen binding
      site) of the coagulation factor. The very stable protein-DNA complex formation is
      the result of complementarities between the two macromolecules promoted by the
      aptamer sequence and folding as well as of electrostatic interactions generated
      by the charge balance at the binding site/s. Here, we investigated the relative
      role of these contributions and their involvement in defining the biological
      properties of the resulting complex. Thus we compared the Thrombin binding and
      inhibition properties of TBA to those of unrelated single stranded
      oligonucleotides. Additionally, the differences between the two protein exosites
      were assessed by using 29hTBA, a longer (29-mer) aptamer known to bind exosite II
      (heparin binding site). A subtle balance of aptamer folding and sequence is shown
      to cooperate with charge density for effective and selective recognition of
      exosite I or exosite II by TBAs.

PMID- 22376115
TI  - The polymorphisms of DNA G-quadruplex investigated by docking experiments with
      telomestatin enantiomers.
AB  - Human telomeres are comprised of d(TTAGGG) repeats involved in the formation of G
      quadruplex DNA structures. Ligands stabilizing these G-quadruplex DNA structures
      are potential inhibitors of the cancer cell-associated enzyme telomerase. In
      human cells, telomerase adds multiple copies of the 5'-GGTTAG-3' motif to the end
      of the G-strand of the telomere and in the majority of tumor cells it results
      over-expressed. Several structural studies have revealed a diversity of
      topologies for telomeric quadruplexes, which are sensitive to the nature of the
      cations present, to the flanking sequences, and probably also to concentration,
      as confirmed by the different conformations deposited in the Protein Data Bank
      (PDB). The existence of different polymorphisms in the DNA quadruplex and the
      absence of a uniquely precise binding site prompted us to carefully compare the
      two different docking approaches: MOLINE and Auto- Dock. As target we have
      selected six different experimental models of the human telomeric sequence
      d[AG3(T2AG3)3] based on three Gtetrads and as ligands the telomestatin isomers,
      whose the S enantomer is experimentally known to recognize the G-quadruplex
      better than the R one. In this communication we discuss the different binding
      modes of the well known strong telomestatin G-quadruplex binder form the
      thermodynamic and the geometrical points of view. With respect to this last issue
      we propose an easy approach to classify binding modes of G-quadruplex ligands
      based on a single angle descriptor as tool for the quick analysis of the binding
      modes.

PMID- 22376116
TI  - Searching drug-like anti-cancer compound(s) based on G-quadruplex ligands.
AB  - G-quadruplex structure is a four-stranded form of DNA, which is associated with
      cancer cell proliferation. G-quadruplex-stabilized ligands have the potential to
      interfere with telomere replication by blocking the elongation procedure
      catalyzed by telomerase, and therefore have the potential to be anti-cancer
      drugs. A considerable number of novel compounds capable of targeting G-quadruplex
      at high affinity and specificity have been reported. Among them, several G
      quadruplex ligands have shown promising anti-cancer activity in tumor xenograft
      models, and entered phase II clinical trials on cancer patients. This review
      summarized recent developments of G-quadruplex ligands as anti-cancer drugs and
      several powerful strategies to discover novel G-quadruplex ligands as anti-cancer
      drug candidates by screening natural product extracts and structural optimization
      of previously identified typical compounds.

PMID- 22376117
TI  - G-quadruplex DNA aptamers and their ligands: structure, function and application.
AB  - Highly specific and tight-binding nucleic acid aptamers have been selected
      against a variety of molecular targets for over 20 years. A significant
      proportion of these oligonucleotides display G-quadruplex structures,
      particularly for DNA aptamers, that enable molecular recognition of their
      ligands. G-quadruplex structures couple a common scaffold to varying loop motifs
      that act in target recognition. Here, we review DNA G-quadruplex aptamers and
      their ligands from a structural and functional perspective. We compare the
      diversity of DNA G-quadruplex aptamers selected against multiple ligand targets,
      and consider structure with a particular focus on dissecting the thrombin binding
      aptamer - thrombin interaction. Therapeutic and analytical applications of DNA G
      quadruplex aptamers are also discussed. Understanding DNA G-quadruplex aptamers
      carries implications not only for therapeutics and diagnostics, but also in the
      natural biochemistry of guanine-rich nucleic acids.

PMID- 22376118
TI  - Screening of a chemical library by HT-G4-FID for discovery of selective G
      quadruplex binders.
AB  - Due to the lack of structural guidelines about G-quadruplex ligands, rational
      design cannot be the only approach to discover potent G4-ligands. As a
      complementary approach, screening of chemical library may provide interesting
      scaffolds known as hits provided that specific tools are available. In this work,
      the Institut Curie-CNRS chemical library was firstly screened by chemoinformatics
      methods. Similarity estimations by comparison with reference compounds (Phen-DC3,
      360A, MMQ12) provided a set of molecules, which were then evaluated by high
      throughput G4-FID (HT-G4-FID) against various G-quadruplex DNA. A full
      investigation of the most interesting molecules, using the HT-G4-FID assay and
      molecular modeling, supplied an interesting structure-activity relationship
      confirming the efficiency of this general approach. Overall, we demonstrated that
      HT-G4-FID coupled with screening of chemical libraries is a powerful tool to
      identify new G4-DNA binding scaffolds.

PMID- 22376119
TI  - Human telomere RNA: a potential target for ligand recognition.
AB  - A recent finding demonstrated that telomere DNA is transcribed into telomeric
      repeat-containing RNA (referred to as TERRA) in mammalian cells. The existence of
      TERRA RNA may reveal a new level of regulation and protection of chromosome ends
      that could promote valuable insight into fundamental biological processes such as
      cancer and aging. Revealing the structure and function of telomere RNA will be
      essential for understanding telomere biology and telomere-related diseases. In
      fact, others and we have shown by NMR and x-ray crystallography that human
      telomere RNA forms G-quadruplex structures. More recently, we found that human
      telomere RNA forms a G-quadruplex dimer in the living cells by employing a light
      switching probe. Recently, researches concerning the telomere RNA G-quadruplexes
      have made much progress. This review highlights the structures and topologies for
      telomere RNA G-quadruplex and recent efforts in the design of telomere RNA G
      quadruplex ligands; outlines the future challenges in the field.

PMID- 22376120
TI  - Free energy difference in indolicidin attraction to eukaryotic and prokaryotic
      model cell membranes.
AB  - We analyzed the thermodynamic and structural determinants of indolicidin
      interactions with eukaryotic and prokaryotic cell membranes using a series of
      atomistically detailed molecular dynamics simulations. We used quartz-supported
      bilayers with two different compositions of zwitterionic and anionic
      phospholipids as model eukaryotic and prokaryotic cell membranes. Indolicidin was
      preferentially attracted to the model prokaryotic cell membrane in contrast to
      the weak adsorption on the eukaryotic membrane. The nature of the indolicidin
      surface adsorption depended on an electrostatic guiding component, an attractive
      enthalpic component derived from van der Waals interactions, and a balance
      between entropic factors related to peptide confinement at the interface and
      counterion release from the bilayer surface. Thus, whereas we attributed the
      specificity of the indolicidin/membrane interaction to electrostatics, these
      interactions were not the sole contributors to the free energy of adsorption.
      Instead, a balance between an attractive van der Waals enthalpic component and a
      repulsive entropic component determined the overall strength of indolicidin
      adsorption.

PMID- 22376122
TI  - Slow resorption of anorganic bovine bone by osteoclasts in maxillary sinus
      augmentation.
AB  - PURPOSE: Different biomaterials have been suggested for guided bone regeneration
      (GBR). These might show the ideal properties to let a new bone formation in the
      grafted area. Among these ideal features, it is essential their controlled
      resorption in order to be replaced for new vital bone. Bovine bone has been used
      widely as a good biomaterial for GBR, however there is still an interesting
      controversy about its resorbable capacity. In this sense, the objective of this
      study was to examine the behavior of anorganic bovine bone (ABB) in long-term
      maxillary sinus graft healing and study its relationship with morphological and
      morphometrical variables. MATERIALS AND METHODS: Seventeen maxillary sinus
      augmentation procedures were performed in patients. Bone cores were obtained from
      implant receptor sites at 6 months, 3 years, and 7 years of implant placement for
      histological, morphometric, and immunohistochemical (tartrate resistant acid
      phosphatase [TRAP]/cathepsin K/CD68) studies. RESULTS: The percentages of bone,
      ABB particles, connective tissue, osteocytes, and osteoblasts in maxillary sinus
      grafts were similar at 6 months, 3 years, and 7 years. A progressive and
      significant decrease was detected in osteoclasts (p = .05, Kruskal-Wallis test),
      TRAP and cathepsin K expression (p = .014 and p = .021, respectively), and
      osteoid lines (p = .038). CONCLUSION: According to these data, a decrease in
      osteoclasts over time may, partially, explain the ABB persistence observed in
      core biopsies. Further studies with more cases and different graft maturation
      times are required to elucidate the resorption rates and cell events underlying
      these phenomena.

PMID- 22376121
TI  - Building the community voice into planning: 25 years of methods development in
      social audit.
AB  - Health planners and managers make decisions based on their appreciation of
      causality. Social audits question the assumptions behind this and try to improve
      quality of available evidence. The method has its origin in the follow-up of
      Bhopal survivors in the 1980s, where "cluster cohorts" tracked health events over
      time. In social audit, a representative panel of sentinel sites are the framework
      to follow the impact of health programmes or reforms. The epidemiological
      backbone of social audit tackles causality in a calculated way, balancing
      computational aspects with appreciation of the limits of the science.Social
      audits share findings with planners at policy level, health services providers,
      and users in the household, where final decisions about use of public services
      rest. Sharing survey results with sample communities and service workers
      generates a second order of results through structured discussions. Aggregation
      of these evidence-based community-led solutions across a representative sample
      provides a rich substrate for decisions. This socialising of evidence for
      participatory action (SEPA) involves a different skill set but quality control
      and rigour are still important.Early social audits addressed settings without
      accepted sample frames, the fundamentals of reproducible questionnaires, and the
      logistics of data turnaround. Feedback of results to stakeholders was at CIET
      insistence--and at CIET expense. Later social audits included strong SEPA
      components. Recent and current social audits are institutionalising high level
      research methods in planning, incorporating randomisation and experimental
      designs in a rigorous approach to causality.The 25 years have provided a number
      of lessons. Social audit reduces the arbitrariness of planning decisions, and
      reduces the wastage of simply allocating resources the way they were in past
      years. But too much evidence easily exceeds the uptake capacity of decision
      takers. Political will of governments often did not match those of donors with
      interest conditioned by political cycles. Some reforms have a longer turnaround
      than the political cycle; short turnaround interventions can develop momentum.
      Experience and specialisation made social audit seem more simple than it is. The
      core of social audit, its mystique, is not easily taught or transferred. Yet
      teams in Mexico, Nicaragua, Canada, southern Africa, and Pakistan all have more
      than a decade of experience in social audit, their in-service training supported
      by a customised Masters programme.

PMID- 22376124
TI  - Sexuality, rights and personhood: tensions in a transnational world.
AB  - BACKGROUND: This article discusses what happens when normative 'global'
      discourses of rights and individuated sexual identity confront the messiness of
      'local' realities. It considers the tensions that emerge when the relationship
      between sexual and social identities is not obvious and the implications of such
      tensions for public health and sexual rights activism. These questions are
      addressed through debates over the naming of male-to-male sexualities and desires
      in the context of globalization and the growth of a large NGO (non-governmental
      organization) sector in urban Bangladesh. METHODS: The material in the paper
      draws on a research project undertaken in 2008-9 in Dhaka, Bangladesh. A
      fundamental objective was to produce a contextualized understanding of sexuality
      in Dhaka city. Methods used included structured interviews, focus group
      discussions and informal conversations with a range of participants (students,
      factory workers, public health professionals and sexual minorities). The aim was
      to generate a conceptual and analytical framework around sexuality and rights
      rather than to undertake an empirical survey of any one population. RESULTS: As
      descriptors, globalized identity categories such as Men who have Sex with Men
      (MSM), used by public health providers, the state and donors; and gay/lesbian,
      invoked by human rights activists and transnational NGOs, are too narrow to
      capture the fluid and highly context-specific ways in which gender and sexually
      nonconforming persons understand themselves in Bangladesh. Further, class
      position mediates to a significant degree the reception, appropriation or
      rejection of transnational categories such as MSM and Lesbian, Gay, Bisexual,
      Transgender (LGBT). The tension is reflected in the sometimes fraught relations
      between service providers to MSM, the people they serve and an emerging group who
      identify as LGBT. CONCLUSION: A simple politics of recognition will be inadequate
      to the task of promoting health and human rights for all; such a strategy would
      effectively exclude individuals who do not necessarily connect their sexual
      practices with a specific sexual or social identity.

PMID- 22376125
TI  - Assessment of bacterial endosymbiont diversity in Otiorhynchus spp. (Coleoptera:
      Curculionidae) larvae using a multitag 454 pyrosequencing approach.
AB  - BACKGROUND: Weevils of the genus Otiorhynchus are regarded as devastating pests
      in a wide variety of horticultural crops worldwide. So far, little is known on
      the presence of endosymbionts in Otiorhynchus spp.. Investigation of
      endosymbiosis in this genus may help to understand the evolution of different
      reproductive strategies in these weevils (parthenogenesis or sexual
      reproduction), host-symbiont interactions, and may provide a future basis for
      novel pest management strategy development. Here, we used a multitag 454
      pyrosequencing approach to assess the bacterial endosymbiont diversity in larvae
      of four economically important Otiorhynchus species. RESULTS: High-throughput tag
      encoded FLX amplicon pyrosequencing of a bacterial 16S rDNA fragment was used to
      characterise bacterial communities associated with different Otiorhynchus spp.
      larvae. By sequencing a total of ~48,000 PCR amplicons, we identified 49
      different operational taxonomic units (OTUs) as bacterial endosymbionts in the
      four studied Otiorhynchus species. More than 90% of all sequence reads belonged
      either to the genus Rickettsia or showed homology to the phylogenetic group of
      "Candidatus Blochmannia" and to endosymbionts of the lice Pedicinus obtusus and
      P. badii. By using specific primers for the genera Rickettsia and "Candidatus
      Blochmannia", we identified a new phylogenetic clade of Rickettsia as well as
      "Candidatus Nardonella" endosymbionts in Otiorhynchus spp. which are closely
      related to "Candidatus Blochmannia" bacteria. CONCLUSIONS: Here, we used multitag
      454 pyrosequencing for assessment of insect endosymbiotic communities in weevils.
      As 454 pyrosequencing generates only quite short sequences, results of such
      studies can be regarded as a first step towards identifying respective
      endosymbiotic species in insects. In the second step of our study, we analysed
      sequences of specific gene regions for a more detailed phylogeny of selected
      endosymbiont genera. As a result we identified the presence of Rickettsia and
      "Candidatus Nardonella" endosymbionts in Otiorhynchus spp.. This knowledge is an
      important step in exploring bacteria-insect associations for potential use in
      insect pest control.

PMID- 22376126
TI  - Rate of introduction of a low pathogenic avian influenza virus infection in
      different poultry production sectors in the Netherlands.
AB  - BACKGROUND: Targeted risk-based surveillance of poultry types (PT) with different
      risks of introduction of low pathogenic avian influenza virus (LPAIv) infection
      may improve the sensitivity of surveillance. OBJECTIVE: To quantify the rate of
      introduction of LPAIv infections in different PT. METHODS: Data from the Dutch
      LPAIv surveillance programme (2007-2010) were analysed using a generalised linear
      mixed and spatial model. RESULTS: Outdoor-layer, turkey, duck-breeder and meat
      duck, farms had a 11, 8, 24 and 13 times higher rate of introduction of LPAIv
      than indoor-layer farms, respectively. CONCLUSION: Differences in the rate of
      introduction of LPAIv could be used to (re)design a targeted risk-based
      surveillance programme.

PMID- 22376127
TI  - Self-management strategies to support performance of daily activities in hand
      osteoarthritis.
AB  - AIMS: The main aim of this study was to explore self-management strategies in
      persons with hand osteoarthritis (HOA). METHODS: Self-management strategies were
      explored in semi-structured interviews, in which 125 participants described
      strategies, use of devices or equipment, and advice they would give to people
      with HOA concerning how to manage their daily life. RESULTS: The participants
      made a total of 483 statements, which were classified into 27 discrete
      strategies, and thereafter grouped into 13 broader strategies within three
      categories: general behavioural strategies, HOA-specific behavioural strategies,
      and cognitive strategies. The broad strategy "activity accommodations"
      specifically addressed performance of daily activities in people with HOA,
      comprising "use assistive devices", "adapt tools, materials or working
      techniques", "practise activity pacing" and "stop or avoid certain activities",
      of which the two first were the most frequently stated by participants.
      CONCLUSIONS: People with HOA use a wide variety of self-management strategies to
      support performance of daily activities, in which use of assistive devices and
      activity adaptation are the most frequently reported strategies. Patient
      recommended self-management strategies should be included in written information
      material and patient education programmes, which should be developed in
      cooperation with patient representatives and made available for patients soon
      after they are diagnosed.

PMID- 22376128
TI  - Ligand effects and ligand design in homogeneous gold(I) catalysis.
AB  - Gold catalysis is considered one of the most important breakthroughs in organic
      synthesis during the past decade, but a rational understanding of ligand effects
      in gold catalysis is lacking. Most gold-catalyzed reactions go through three
      major stages: (i) electronic activation of alkyne (or allene) to generate a vinyl
      gold intermediate; (ii) protodeauration to generate the product and regenerate
      the cationic gold catalyst; (iii) decay of the active gold catalyst. Our research
      provides a clearer understanding of how ligands influence each of the three
      stages in the gold catalytic cycle. What is even more important, by not focusing
      on a particular gold-catalyzed reaction, we have been able to categorize most
      gold-catalyzed reactions and propose a ligand design protocol for each category
      of gold-catalyzed reactions.

PMID- 22376129
TI  - Fluorescent pigment and phenol glucosides from the heartwood of Pterocarpus
      marsupium.
AB  - The fluorescence shown by extracts of the heartwood of Pterocarpus marsupium is
      attributed to salts of the new compound 1, whose structure was elaborated using
      detailed spectroscopic/spectrometric studies. The plant material also contains
      the nonfluorescent compounds 2 and 3. The absolute configuration of 1 was
      determined by experimental and theoretically calculated electronic CD spectra,
      while that of 3 was deduced from ECD comparison with reported results in the
      alpha-hydroxydihydrochalcone series.

PMID- 22376130
TI  - Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion
      imaging for prediction of neurovascular uncoupling potential in brain tumors.
AB  - The coupling mechanism between neuronal firing and cerebrovascular dilatation can
      be  significantly compromised in cerebral diseases, making it difficult to
      identify eloquent cortical areas near or within resectable lesions by using Blood
      Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have
      been considered to account for this lesion-induced neurovascular uncoupling
      (NVU), but no imaging gold standard exists currently for the detection of NVU.
      However, it is critical in clinical fMRI studies to evaluate the risk of NVU
      because the presence of NVU may result in false negative activation that may
      result in inadvertent resection of eloquent cortex, resulting in permanent
      postoperative neurologic deficits. Although NVU results from a disruption of one
      or more components of a complex cellular and chemical neurovascular coupling
      cascade (NCC) MR imaging is only able to evaluate the final step in this NCC
      involving the ultimate cerebrovascular response. Since anything that impairs
      cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of
      its effect more proximally along the NCC, we can consider mapping of CVR as a
      surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR
      mapping can serve as a better marker of NVU potential than T2* Dynamic
      Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is
      known to only reflect NVU risk associated with high grade gliomas by determining
      elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow
      (rCBF) related to tumor angiogenesis. However, since low and intermediate grade
      gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping
      may be able to detect such NVU potential even in lower grade gliomas without
      angiogenesis, which is the hallmark of glioblastomas. However, it is also known
      that glioblastomas are associated with variable NVU, since angiogenesis may not
      always result in NVU. Perfusion metrics obtained by T2* gadolinium perfusion MR
      imaging were compared to BOLD percentage signal change on BH CVR maps in a group
      of 19 patients with intracranial brain tumors of different nature and grade.
      Single pixel maximum rCBV and rCBF within holotumoral regions of interest (i.e.,
      "ipsilesional" ROIs) were normalized to contralateral hemispheric homologous
      (i.e., "contralesional") normal tissue. Furthermore, percentage signal change on
      BH CVR maps within ipsilesional ROIs were normalized to the percentage signal
      change within contralesional homologous ROIs. Inverse linear correlation was
      found between normalized rCBF (r(flow)) or rCBV (r(vol)) and normalized CVR
      percentage signal change (r(CVR)) in grade IV lesions. In the grade III lesions a
      less steep inverse linear trend was seen that did not reach statistical
      significance, whereas no correlation at all was seen in the grade II group.
      Statistically significant difference was present for r(flow) and r(vol) between
      the grade II and IV groups and between the grade III and IV groups but not for
      r(CVR). The r(CVR) was significantly lower than 1 in every group. Our results
      demonstrate that while T2*MR perfusion maps and CVR maps are both adequate to map
      tumoral regions at risk of NVU in high grade gliomas, CVR maps can detect areas
      of decreased CVR also in low and intermediate grade gliomas where NVU may be
      caused by factors other than tumor neovascularity alone. Comparison of areas of
      abnormally decreased regional CVR with areas of absent BOLD task-based activation
      in expected eloquent cortical regions infiltrated by or adjacent to the tumors
      revealed overall 95% concordance, thus confirming the capability of BH CVR
      mapping to effectively demonstrate areas of NVU. ed by factors other than tumor
      neovascularity alone. Comparison of areas of abnormally decreased regional CVR
      with areas of absent BOLD task-based activation in expected eloquent cortical
      regions infiltrated by or adjacent to the tumors revealed overall 95%
      concordance, thus confirming the capability of BH CVR mapping to effectively
      demonstrate areas of NVU.

PMID- 22376131
TI  - Feasibility study of a novel rotational and translational method for linac-based
      intensity modulated total marrow irradiation.
AB  - Conventional TBI is primarily limited by the toxicity to organs at risk because
      of impossibility of sparing critical organs. The purpose of this study is to
      investigate the feasibility of a novel rotational and translational IMRT method
      (RTM) which able to conform the radiation dose to target organs and reduce
      critical organ dose for TMI using linac. To assess the feasibility, we
      investigated the planning and delivery of total marrow irradiation (TMI) using
      this method. The treatment plannig study showed that target coverage was achieved
      with 90% of the target volume receiving 100% of the prescription dose. Doses to
      critical structures indicated that a 1.28- to 2.35-fold reduction in median dose
      is achieved with total-marrow RTM compared with conventional TBI. Delivery of
      Rando phantom and TLD measurement demonstrated an accurate dose delivery (ranged
      from -6% to 7%) to the target and critical organs. Results from this study
      suggests that RTM can be accurately delivered and reduce irradiation to all
      critical organs with good target coverage.

PMID- 22376132
TI  - Cone beam CT (CBCT) evaluation of inter- and intra-fraction motion for patients
      undergoing brain radiotherapy immobilized using a commercial thermoplastic mask
      on a robotic couch.
AB  - Patients receiving fractionated intensity-modulated radiation therapy (IMRT) for
      brain tumors are often immobilized with a thermoplastic mask; however, masks do
      not perfectly re-orient the patient due to factors including the maximum pressure
      which can be applied to the face, deformations of the mask assembly, patient
      compliance, etc. Consequently, ~3-5mm PTV margins (beyond the CTV) are often
      recommended. We aimed to determine if smaller PTV margins are feasible using mask
      immobilization coupled with 1) a gantry mounted CBCT image guidance system and 2)
      position corrections provided by a full six-degree of freedom (6-DOF) robotic
      couch. A cohort of 34 brain tumor patients was treated with fractionated IMRT.
      After the mask set-up, an initial CBCT was obtained and registered to the
      planning CT. The robotic couch corrected the misalignments in all 6-DOF and a pre
      treatment verification CBCT was then obtained. The results indicated a
      repositioning alignment within our threshold of 1.5 mm (3D). Treatment was
      subsequently delivered. A post-treatment CBCT was obtained to quantify intra
      fraction motion. Initial, pre-treatment and post-treatment CBCT image data was
      analyzed. A total of 505 radiation fractions were delivered to the 34 patients
      resulting in ~1800 CBCT scans. The initial median 3D (magnitude) set-up
      positioning error was 2.60 mm. Robotic couch corrections reduced the 3D median
      error to 0.53 mm prior to treatment. Intra-fraction movement was responsible for
      increasing the median 3D positioning error to 0.86 mm, with 8% of fractions
      having a 3D positioning error greater than 2 mm. Clearly CBCT image guidance
      coupled with a robotic 6-DOF couch dramatically improved the positioning accuracy
      for patients immobilized in a thermoplastic mask system; however, such intra
      fraction motion would be too large for single fraction radiosurgery.

PMID- 22376133
TI  - Adjustment of ultrasound exposure duration to microbubble sonodestruction
      kinetics for optimal cell sonoporation in vitro.
AB  - Cell sonoporation enables the delivery of various exogenous molecules into the
      cells. To maximize the percentage of reversibly sonoporated cells and to increase
      cell viability we propose a model for implicit dosimetry for adjustment of
      ultrasound (US) exposure duration. The Chinese hamster ovary cell suspension was
      supplemented with microbubbles (MB) and exposed to US, operating at the frequency
      of 880kHz, with a 100% duty cycle and with an output peak negative pressure (PNP)
      of 500kPa for durations ranging from 0.5 to 30s. Using diagnostic B-scan imaging
      we showed that the majority of the MB at 500kPa US peak negative pressure undergo
      sonodestruction in less than a second. During this time maximal number of
      reversibly sonoporated cells was achieved. Increase of US exposure duration did
      not increase sonoporated cell number, however it induced additional cell
      viability decrease. Therefore aiming to achieve the highest level of reversibly
      sonoporated cells and also to preserve the highest level of cell viability, the
      duration of US exposure should not exceed the duration needed for complete MB
      sonodestruction.

PMID- 22376134
TI  - Single arc volumetric modulated arc therapy for complex brain gliomas: is there
      an advantage as compared to intensity modulated radiotherapy or by adding a
      partial arc?
AB  - The objective of this study was to determine if volumetric modulated arc therapy
      (VMAT) offers advantages over intensity modulated radiotherapy (IMRT) for complex
      brain gliomas and evaluate the role of an additional partial arc. Twelve patients
      with glioma involving critical organs at risk (OAR) were selected [six low grade
      brainstem glioma (BG) and six glioblastoma (GB) cases]. BGs were prescribed 54
      Gy/30 fractions (frx), and GB treated to 50 Gy/30 frx to a lower dose PTV (PTV50)
      with a simultaneous integrated boost delivering a total dose of 60 Gy/30 frx to a
      higher dose PTV (PTV60). VMAT was planned with a single arc (VMAT1) and with an
      additional coplanar partial arc spanning 90 degrees  (VMAT2). We observed VMATI
      improving the PTV equivalent uniform dose (EUD) for BG cases (p=0.027), improving
      the V95 for the PTV50 in GB cases (p=0.026) and resulting in more conformal GB
      plans (p=0.008) as compare to IMRT. However, for the GB PTV60, IMRT achieved
      favorable V95 over VMAT1 and VMAT2 (0.0046 and 0.008, respectively). The GB total
      integral dose (ID) was significantly lower with VMAT1 and VMAT2 (p=0.049 and
      p=0.006, respectively). Both VMAT1 and VMAT2 reduced the ID, however, only at the
      5 Gy threshold for BG cases (p=0.011 and 0.005, respectively). VMAT achieved a
      lower spinal cord maximum dose and EUD for BG cases and higher optic nerve doses,
      otherwise no significant differences were observed. VMAT1 yielded the fastest
      treatment times and least MU. We conclude that VMAT offers faster treatment
      delivery for complex brain tumors while maintaining similar dosimetric qualities
      to IMRT. Selective dosimetric advantages in terms of spinal cord sparing and
      lowering the ID are observed favoring the use of an additional coplanar partial
      arc.

PMID- 22376135
TI  - WOMAC-pf as a measure of physical function in patients with Parkinson's disease
      and late-onset sequels of poliomyelitis: unidimensionality and item behaviour.
AB  - PURPOSE: To assess psychometric properties of the Western Ontario and MacMasters
      Universities Osteoarthritis Index (WOMAC)-pf, an osteoarthritis (OA)-specific
      questionnaire used to establish the level of physical functioning in patients
      with late-onset sequels of poliomyelitis (LOSP) and Parkinson's disease (PD).
      STUDY DESIGN AND SETTING: Unidimensionality (using principal component analyses
      [PCA] and Rasch analyses) was separately established for three diagnostic groups:
      OA (n = 288), LOSP (n = 168) and PD (n = 200). Additionally, differential item
      functioning (DIF) among the three diagnostic groups was assessed using ordinal
      regression (Polytomous Universal Model) analyses. Baseline data were used from an
      ongoing cohort study of these three patient populations. RESULTS:
      Unidimensionality was adequate, with all items loading on the first principal
      component. The Rasch analyses revealed that item fit was generally good. Uniform
      and non-uniform DIF were found to be present among the three diagnostic groups in
      three and one of the 17 physical functioning subscale (WOMAC-pf) items,
      respectively. CONCLUSION: The WOMAC-pf is a unidimensional measure of physical
      functioning in patients with LOSP and PD, in addition to its established use in
      OA. [ IMPLICATIONS FOR REHABILITATION: * Disability in physical functioning
      related to mobility(walking, stair climbing, etc.) is a common feature of many
      chronic diseases, including osteoarthritis, late-onset sequels of poliomyelitis
      and Parkinson's disease.* In this study, the Western Ontario and MacMasters
      Universities Osteoarthritis Index-pf was shown to bea useful and adequate tool to
      assess physical functioning in these patient groups.* The study highlighted that,
      despite differences in diagnosis,history and course of the disease, patients with
      different conditions experience similar disabilities in their physical
      functioning.]

PMID- 22376136
TI  - Mode of action of a family 75 chitosanase from Streptomyces avermitilis.
AB  - Chitooligosaccharides (CHOS) are oligomers composed of glucosamine and N
      acetylglucosamine with several interesting bioactivities that can be produced
      from enzymatic cleavage of chitosans. By controlling the degree of acetylation of
      the substrate chitosan, the enzyme, and the extent of enzyme degradation, CHOS
      preparations with limited variation in length and sequence can be produced. We
      here report on the degradation of chitosans with a novel family 75 chitosanase,
      SaCsn75A from  Streptomyces avermitilis . By characterizing the CHOS
      preparations, we have obtained insight into the mode of action and subsite
      specificities of the enzyme. The degradation of a fully deacetylated and a 31%
      acetylated chitosan revealed that the enzyme degrade these substrates according
      to a nonprocessive, endo mode of action. With the 31% acetylated chitosan as
      substrate, the kinetics of the degradation showed an initial rapid phase,
      followed by a second slower phase. In the initial faster phase, an acetylated
      unit (A) is productively bound in subsite -1, whereas deacetylated units (D) are
      bound in the -2 subsite and the +1 subsite. In the slower second phase, D-units
      bind productively in the -1 subsite, probably with both acetylated and
      deacetylated units in the -2 subsite, but still with an absolute preference for
      deacetylated units in the +1 subsite. CHOS produced in the initial phase are
      composed of deacetylated units with an acetylated reducing end. In the slower
      second phase, higher amounts of low DP fully deacetylated oligomers (dimer and
      trimer) are produced, while the higher DP oligomers are dominated by compounds
      with acetylated reducing ends containing increasing amounts of internal
      acetylated units. The degradation of chitosans with varying degrees of
      acetylation to maximum extents of degradation showed that increasingly longer
      oligomers are produced with increasing degree of acetylation, and that the longer
      oligomers contain sequences of consecutive acetylated units interspaced by single
      deacetylated units. The catalytic properties of SaCsn75A differ from the
      properties of a previously characterized family 46 chitosanase from  S.
      coelicolor  (ScCsn46A).

PMID- 22376137
TI  - Genome-wide analysis of the MADS-box gene family in cucumber.
AB  - MADS-box transcription factors are known to be involved in many important
      processes during plant growth and development. To date, few cucumber MADS-box
      genes and little tissue expression profiling have been reported. Recent
      completion of the cucumber whole-genome sequencing has allowed genome-wide
      analysis of the MADS-box gene family in cucumber as well as its comparison with
      other species. Here, we performed comprehensive analyses of the 43 cucumber MADS
      box genes and compared them with those in Arabidopsis, poplar, and grapevine. The
      phylogenetic analysis showed that most cucumber members were comparable with
      those in other species, with the exception of AG members. At the same time, the
      three subfamilies FLC, AGL12, and Bs were absent in the cucumber genome. The
      conserved motif analysis revealed that most motifs outside the MADS domain were
      distributed only in specific groups. The analysis of chromosomal localization
      suggested that tandem duplication might contribute to the MADS-box gene
      expansion. Expression analysis revealed that 42 of 43 cucumber MADS-box members
      were expressed in multiple plant tissues, thereby implying their various roles in
      plants.

PMID- 22376138
TI  - Characterisation of aflatoxin and deoxynivalenol exposure among pregnant Egyptian
      women.
AB  - Mycotoxins such as the aflatoxins and deoxynivalenol (DON) are frequent
      contaminants of food. Aflatoxin B1 (AFB1) and DON affect the immune system and
      restrict growth; additionally AFB1 is carcinogenic. To date there are limited
      descriptive biomarker data concerning maternal exposures during pregnancy, and
      none on co-exposures to these mycotoxins. This survey was a cross-sectional
      assessment providing descriptive data on the concentrations of serum aflatoxin
      albumin (AF-alb), urinary aflatoxin M1 (AFM1), and urinary DON for 98 pregnant
      women from Egypt, in relation to diet and socioeconomic status, during the third
      trimester. AF-alb was detected in 34 of 98 (35%) samples, geometric mean (GM) of
      positives = 4.9 pg AF-lys mg(-1) albumin (95% confidence interval (CI) = 4.1-5.8
      pg mg(-1)), and AFM1 in 44 of 93 (48%) samples, GM of positives = 19.7 pg mg(-1)
      creatinine (95%CI = 14.8-26.3 pg mg(-1)). AF-alb and AFM1 levels were positively
      correlated (R = 0.276, p = 0.007). DON was detected in 63 of 93 (68%), GM of
      positives = 2.8 ng mg(-1) (95%CI = 2.1-3.6 ng mg(-1)). Aflatoxin and DON
      biomarkers were observed in 41% of the subjects concurrently. The frequency and
      level of these biomarkers in Egyptian women were modest compared with known high
      risk countries. However, this study represents the first biomarker survey to
      report on the occurrence of DON biomarkers in an African population, in addition
      to the co-occurrence of these two potent mycotoxins. This combined exposure may
      be of particular concern during pregnancy given the potential of toxin transfer
      to the foetus.

PMID- 22376139
TI  - Brominated flame retardants and dechlorane plus in the marine atmosphere from
      Southeast Asia toward Antarctica.
AB  - The occurrence, distribution, and temperature dependence in the marine atmosphere
      of several alternative brominated flame retardants (BFRs), Dechlorane Plus (DP)
      and polybrominated diphenyl ethers (PBDEs) were investigated during a sampling
      cruise from the East Indian Archipelago toward the Indian Ocean and further to
      the Southern Ocean. Elevated concentrations were observed over the East Indian
      Archipelago, especially of the non-PBDE BFR hexabromobenzene (HBB) with
      concentrations up to 26 pg m(-3) which were found to be related to continental
      air masses from the East Indian Archipelago. Other alternative BFRs-
      pentabromotoulene (PBT), pentabromobenzene (PBBz), and 2,3-dibromopropyl-2,4,6
      tribromophenyl ether (DPTE)-were elevated, too, with concentrations up to 2.8,
      4.3, and 2.3 pg m(-3), respectively. DP was detected from 0.26 to 11 pg m(-3) and
      bis-(2-ethylhexyl)-tetrabromophthalate (TBPH) ranged from not detected (nd) to
      2.8 pg m(-3), respectively. PBDEs ranged from nd to 6.6 pg m(-3) (Sigma(10)PBDEs)
      with the highest individual concentrations for BDE-209. The approach of Clausius
      Clapeyron (CC) plots indicates that HBB is dominated by long-range atmospheric
      transport at lower temperatures over the Indian and Southern Ocean, while
      volatilization processes and additional atmospheric emissions dominate at higher
      temperatures. In contrast, BDE-28 and -47 are dominated by long-range transport
      without fresh emissions over the entire cruise transect and temperature range,
      indicating limited fresh emissions of the meanwhile classic PBDEs.

PMID- 22376140
TI  - Occipital nerve stimulation for medically refractory hypnic headache.
AB  - OBJECTIVE: Hypnic headache is a rare, primary headache disorder that exclusively
      occurs regularly during sleep. We present a case of hypnic headache successfully
      managed with occipital nerve stimulation. MATERIALS AND METHODS: A 64-year-old
      female presented with a four-year history of a right occipital headache that
      regularly awakened her from sleep. The headache, which was dull and throbbing,
      would awaken her regularly at 4:00 am, five hours after bedtime at 11:00 pm. No
      photophobia, nausea or vomiting, lacrimation, or other autonomic symptoms were
      present. The headache was refractory to various medical treatments, including
      indomethacin, flunarizine, propranolol. She underwent a trial of occipital nerve
      stimulation with a lead electrode using a medial approach. RESULTS: During the
      ten-day trial stimulation, she reported almost complete relief from hypnic
      headache. Chronic occipital nerve stimulation replicated the trial results. The
      attacks of hypnic headache recurred in one year with loss of stimulation-induced
      paresthesia; a subsequent x-ray showed electrode migration. After revision of the
      electrode to the original location, the effectiveness of the occipital nerve
      stimulation against hypnic headache was achieved again, and this effect has been
      consistent through 36 months of follow-up. CONCLUSION: Occipital nerve
      stimulation was effective in a patient with chronic, refractory hypnic headache.

PMID- 22376141
TI  - The role of the nurse in emergency preparedness.

PMID- 22376142
TI  - Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle.
AB  - Besides being extensively applied as therapeutical remedies, glucocorticoids
      (GCs) - most notably dexamethasone or prednisolone - are also illegally used in
      livestock for growth-promoting purposes. This study was designed to assess the
      suitability of liver tyrosine aminotransferase (TAT), a gluconeogenic enzyme
      known to be induced by GCs, to act as a reliable candidate biomarker to screen
      for GC abuse in cattle. Enzyme activity was measured spectrophotometrically in
      liver cytosols or in cell extracts, and TAT gene expression was determined by
      real-time PCR. Compared with untreated veal calves, a notable scatter (20-fold)
      and much higher median values (3-fold) characterized TAT specific activity in
      liver samples from commercially farmed veal calves. A time-related increase in
      both enzyme activity and gene expression was detected in rat hepatoma cell lines
      treated with dexamethasone concentrations (10(-8) or 10(-9) m) in the range of
      those recorded in noncompliant samples from EU official controls. In experimental
      studies in which finishing bulls were administered GCs at growth-promoting
      dosages, however, no such changes were recorded in dexamethasone-treated animals;
      a statistically significant rise in liver TAT activity (+95%) only occurred in
      prednisolone-treated bulls. Although further research is needed to characterize
      the GC-mediated response in cattle liver, TAT does not appear to be a specific
      and sensitive biomarker of GC abuse in the bovine species.

PMID- 22376143
TI  - Field testing of a multicriteria decision analysis (MCDA) framework for coverage
      of a screening test for cervical cancer in South Africa.
AB  - BACKGROUND: Systematic and transparent approaches to priority setting are needed,
      particularly in low-resource settings, to produce decisions that are sound and
      acceptable to stakeholders. The EVIDEM framework brings together Health
      Technology Assessment (HTA) and multi-criteria decision analysis (MCDA) by
      proposing a comprehensive set of decision criteria together with standardized
      processes to support decisionmaking. The objective of the study was to field test
      the framework for decisionmaking on a screening test by a private health plan in
      South Africa. METHODS: Liquid-based cytology (LBC) for cervical cancer screening
      was selected by the health plan for this field test. An HTA report structured by
      decision criterion (14 criteria organized in the MCDA matrix and 4 contextual
      criteria) was produced based on a literature review and input from the health
      plan. During workshop sessions, committee members 1) weighted each MCDA decision
      criterion to express their individual perspectives, and 2) to appraise LBC,
      assigned scores to each MCDA criterion on the basis of the by-criterion HTA
      report.Committee members then considered the potential impacts of four contextual
      criteria on the use of LBC in the context of their health plan. Feedback on the
      framework and process was collected through discussion and from a questionnaire.
      RESULTS: For 9 of the MCDA matrix decision criteria, 89% or more of committee
      members thought they should always be considered in decisionmaking. Greatest
      weights were given to the criteria "Budget impact", "Cost-effectiveness" and
      "Completeness and consistency of reporting evidence". When appraising LBC for
      cervical cancer screening, the committee assigned the highest scores to
      "Relevance and validity of evidence" and "Disease severity". Combination of
      weights and scores yielded a mean MCDA value estimate of 46% (SD 7%) of the
      potential maximum value. Overall, the committee felt the framework brought
      greater clarity to the decisionmaking process and was easily adaptable to
      different types of health interventions. CONCLUSIONS: The EVIDEM framework was
      easily adapted to evaluating a screening technology in South Africa, thereby
      broadening its applicability in healthcare decision making.

PMID- 22376144
TI  - State-of-the art comparability of corrected emission spectra. 2. Field laboratory
      assessment of calibration performance using spectral fluorescence standards.
AB  - In the second part of this two-part series on the state-of-the-art comparability
      of corrected emission spectra, we have extended this assessment to the broader
      community of fluorescence spectroscopists by involving 12 field laboratories that
      were randomly selected on the basis of their fluorescence measuring equipment.
      These laboratories performed a reference material (RM)-based fluorometer
      calibration with commercially available spectral fluorescence standards following
      a standard operating procedure that involved routine measurement conditions and
      the data evaluation software LINKCORR developed and provided by the Federal
      Institute for Materials Research and Testing (BAM). This instrument-specific
      emission correction curve was subsequently used for the determination of the
      corrected emission spectra of three test dyes, X, QS, and Y, revealing an average
      accuracy of 6.8% for the corrected emission spectra. This compares well with the
      relative standard uncertainties of 4.2% for physical standard-based spectral
      corrections demonstrated in the first part of this study (previous paper in this
      issue) involving an international group of four expert laboratories. The
      excellent comparability of the measurements of the field laboratories also
      demonstrates the effectiveness of RM-based correction procedures.

PMID- 22376146
TI  - Individual and parental factors related to meaning in life among Hungarian
      minority adolescents from Romania.
AB  - Understanding how adolescents achieve meaning in life has important implications
      for their psychological development. A social cognitive model of meaning
      development was tested by assessing psychological (self-efficacy, self-regulation
      and social comparison) and parental (parental responsiveness, demandingness, and
      social support) variables in a sample of 1944 adolescents (aged 15-19 years;
      47.8% males) from secondary schools of the Middle Transylvanian Region, Romania.
      Both psychological and parental factors were significantly related to meaning in
      life. For both boys and girls, self-efficacy, self-regulation, and maternal
      responsiveness related positively with meaning in life, and paternal
      demandingness related inversely to meaning in life. However, social comparison
      related positively to meaning only among boys, and paternal responsiveness
      related positively to meaning only among girls. Results point to a possible
      meaning-supporting role played by social cognitive variables, as well as parental
      autonomy support. The gender differences observed here suggest that existing
      theories of meaning development may need to be elaborated to include family of
      origin and gender. 

PMID- 22376145
TI  - Encapsulating immunostimulatory CpG oligonucleotides in listeriolysin O-liposomes
      promotes a Th1-type response and CTL activity.
AB  - Immunostimulatory sequences (ISS) are short DNA sequences containing unmethylated
      CpG dimers that have multiple effects on the host immune system, including the
      ability to stimulate antigen-specific cytotoxic T lymphocytes (CTLs) and drive
      Th1-type immune responses. Listeriolysin O (LLO)-containing pH-sensitive
      liposomes have been shown to efficiently deliver macromolecules to the cytosol of
      APCs and efficiently stimulate CTLs. We hypothesized that encapsulating ISS
      oligodeoxyribonucleotides (ODNs) in this delivery system would enhance the cell
      mediated immune response and skew Th1-type responses in protein antigen-based
      vaccination utilizing LLO-liposomes. In vitro studies indicated that
      coencapsulation of ISS in LLO-liposomes engendered activation of the NF-kappaB
      pathway while maintaining the efficient cytosolic delivery of antigen mediated by
      the coencapsulated LLO. Antigen-specific CTL responses monitored by using the
      model antigen ovalbumin (OVA) in mice were enhanced when mice were immunized with
      OVA and ISS-ODN-containing LLO-liposomes compared with those immunized with OVA
      containing LLO-liposomes. The enhanced immune responses were of the Th1-type as
      monitored by the robust OVA-specific IgG2a induction and the OVA CD8 peptide
      stimulated IFN-gamma secretion. Our study suggests that including ISS-ODN in LLO
      containing pH-sensitive liposomes yields a vaccine delivery system that enhances
      the cell-mediated immune response and skews this response toward the Th1-type.

PMID- 22376147
TI  - The role of statin therapy in the prevention of atrial fibrillation: a meta
      analysis of randomized controlled trials.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Atrial fibrillation (AF) is the most
      common clinically significant cardiac arrhythmia, and AF is associated with
      relatively higher all-cause mortality in both men and women. However, there are
      limited treatment options for AF. Statins are hypothesized to have a benefit
      against arrhythmias in addition to well-established secondary prevention benefit
      for atherosclerotic coronary artery disease, yet the data are inconsistent WHAT
      THIS STUDY ADDS: Statin therapy was significantly associated with a decreased
      risk of incidence or recurrence of AF. The benefit of statin therapy seemed more
      markedly in secondary prevention than primary prevention. These results provided
      some evidence for the benefit of statins beyond their lipid-lowering activity
      AIMS: The use of statins has been suggested to protect against atrial
      fibrillation (AF) in some clinical observational and experimental studies but has
      remained inadequately explored. This study was designed to examine whether
      statins can reduce the risk of AF. METHODS: Meta-analysis of randomized,
      controlled trials with use of statins on incidence or recurrence of AF was
      performed. RESULTS: Twenty studies with 23,577 patients were included in the
      analysis. Seven studies investigated the use of statins in patients with AF, 11
      studies investigated the primary prevention of statins in patients without AF,
      and two studies investigated mixed populations of patients. The incidence or
      recurrence of AF occurred in 1543 patients. Overall, statin therapy was
      significantly associated with a decreased risk of AF compared with control (odds
      ratio 0.49, 95% confidence interval 0.37-0.65; P < 0.00001). A beneficial effect
      was found in the atorvastatin subgroup and the simvastatin subgroup, but not in
      the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin
      therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34,
      95% confidence interval 0.18-0.64; P < 0.0008) than in primary prevention (odds
      ratio 0.54, 95% confidence interval 0.40-0.74; P < 0.0001). CONCLUSIONS: Statin
      therapy was significantly associated with a decreased risk of incidence or
      recurrence of AF. Heterogeneity was explained by differences in statin types,
      patient populations and surgery types. The benefit of statin therapy seemed more
      pronounced in secondary than in primary prevention.

PMID- 22376149
TI  - The role of obesity in the development of polycystic ovary syndrome.
AB  - Polycystic Ovary Syndrome (PCOS) is one of the common endocrine diseases that
      affects women in their reproductive age. PCOS has diverse clinical implications
      that include reproductive (infertility, hyperandrogenism, hirsutism), metabolic
      (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus,
      cardiovascular diseases) and psychological features (increased anxiety,
      depression and worsened quality of life). The exact patho-physiology of PCOS is
      complex and remains largely unclear. The prevalence of PCOS is estimated at 4
      18%, depending on diverse factors discussed ahead. The phenotype varies widely
      depending on life stage, genotype, ethnicity and environmental factors including
      lifestyle and body weight. During the last decades, obesity and excess weight are
      major chronic diseases all around the word. Obesity increases some features of
      PCOS such as hyperandrogenism, hirsutism, infertility and pregnancy
      complications. Both obesity and insulin resistance increase diabetes mellitus
      type 2 and cardiovascular diseases. Moreover, obesity impairs insulin resistance
      and exacerbates reproductive and metabolic features of PCOS. It is well known
      that obesity is associated with anovulation, pregnancy loss and late pregnancy
      complications (pre-eclampsia, gestational diabetes). Obesity in PCOS is also
      linked to failure or delayed response to the various treatments including
      clomiphene citrate, gonadotropins and laparoscopic ovarian diathermy. It has been
      reported that, after losing as little as 5 % of initial body weight obese women
      with PCOS improved spontaneous ovulation rates and spontaneous pregnancy.
      Therefore, the weight loss prior to conception improves live birth rate in obese
      women with or without PCOS. The treatment of obesity may include lifestyle
      therapy (diet and exercise), pharmacological treatment and bariatric surgery. In
      summary, weight loss is considered the first-line therapy in obese women with
      PCOS. In the present review, the consequence and treatment of obesity in women
      with PCOS are discussed.

PMID- 22376151
TI  - Temperature pulsing for controlling chromatographic resolution in capillary
      liquid chromatography.
AB  - In this study we introduce the implementation of rapid temperature pulses for
      selectivity tuning in capillary liquid chromatography. Short temperature pulses
      improved resolution in discrete sections of chromatograms, demonstrated for ion
      exchange chromatography (IC) and hydrophilic interaction chromatography (HILIC)
      modes. Using a resistively heated column module capable of accurate and rapid
      temperature changes, this concept is first illustrated with separations of small
      anions by IC using a packed capillary column as well as a series of nucleobases
      and nucleosides by HILIC using a silica monolithic column with zwitterionic
      functionality (ZIC-HILIC). Both positive (increasing temperature) and negative
      temperature pulses are demonstrated to produce significant changes in selectivity
      and are useful approaches for improving resolution between coeluted compounds.
      The approach was shown to be reproducible over a large number of replicates.
      Finally, the use of temperature gradients as well as other complex temperature
      profiles was also examined for both IC and HILIC separations.

PMID- 22376150
TI  - Bayesian lasso for semiparametric structural equation models.
AB  - There has been great interest in developing nonlinear structural equation models
      and associated statistical inference procedures, including estimation and model
      selection methods. In this paper a general semiparametric structural equation
      model (SSEM) is developed in which the structural equation is composed of
      nonparametric functions of exogenous latent variables and fixed covariates on a
      set of latent endogenous variables. A basis representation is used to approximate
      these nonparametric functions in the structural equation and the Bayesian Lasso
      method coupled with a Markov Chain Monte Carlo (MCMC) algorithm is used for
      simultaneous estimation and model selection. The proposed method is illustrated
      using a simulation study and data from the Affective Dynamics and Individual
      Differences (ADID) study. Results demonstrate that our method can accurately
      estimate the unknown parameters and correctly identify the true underlying model.

PMID- 22376152
TI  - Can rights stop the wrongs? Exploring the connections between framings of sex
      workers' rights and sexual and reproductive health.
AB  - BACKGROUND: There is growing interest in the ways in which legal and human rights
      issues related to sex work affect sex workers' vulnerability to HIV and abuses
      including human trafficking and sexual exploitation. International agencies, such
      as UNAIDS, have called for decriminalisation of sex work because the delivery of
      sexual and reproductive health services is affected by criminalisation and social
      exclusion as experienced by sex workers. The paper reflects on the connections in
      various actors' framings between sex workers sexual and reproductive health and
      rights (SRHR) and the ways that international law is interpreted in policing and
      regulatory practices. METHODS: The literature review that informs this paper was
      carried out by the authors in the course of their work within the Paulo Longo
      Research Initiative. The review covered academic and grey literature such as
      resources generated by sex worker rights activists, UN policy positions and print
      and online media. The argument in this paper has been developed reflectively
      through long term involvement with key actors in the field of sex workers'
      rights. RESULTS: International legislation characterises sex work in various ways
      which do not always accord with moves toward decriminalisation. Law, policy and
      regulation at national level and law enforcement vary between settings. The
      demands of sex worker rights activists do relate to sexual and reproductive
      health but they place greater emphasis on efforts to remove the structural
      barriers that limit sex workers' ability to participate in society on an equal
      footing with other citizens. DISCUSSION AND CONCLUSION: There is a tension
      between those who wish to uphold the rights of sex workers in order to reduce
      vulnerability to ill-health and those who insist that sex work is itself a
      violation of rights. This is reflected in contemporary narratives about sex
      workers' rights and the ways in which different actors interpret human rights
      law. The creation of regulatory frameworks around sex work that support health,
      safety and freedom from abuse requires a better understanding of the broad scope
      of laws, policies and enforcement practices in different cultural contexts and
      economic settings, alongside reviews of UN policies and human rights conventions.

PMID- 22376154
TI  - CXCR4 inhibitors: tumor vasculature and therapeutic challenges.
AB  - CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors
      CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue
      and is involved in the outgrowth and metastasis of CXCR4 expressing tumors.
      Recent investigations have indicated that CXCL12 levels increase after chemo- and
      anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has
      emerged as a potential additional or alternative target for neo-adjuvant
      treatments. We have reviewed recent patent applications between 2008 and 2011 in
      tumor angiogenesis and the most clinical data supporting the potential use of
      anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform
      (Mozobil by Genzyme), is approved for stem cell mobilisation in patients with
      leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054
      (ChemoCentryx) are currently in clinical trials in combination with chemotherapy
      for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for
      chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials
      for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx)
      is still in preclinical studies. We have also considered other strategies, such
      RNA interference and miRNA, which could be tested for solid tumor adjuvant
      therapy.

PMID- 22376153
TI  - Influence of Wolbachia on host gene expression in an obligatory symbiosis.
AB  - BACKGROUND: Wolbachia are intracellular bacteria known to be facultative
      reproductive parasites of numerous arthropod hosts. Apart from these reproductive
      manipulations, recent findings indicate that Wolbachia may also modify the host's
      physiology, notably its immune function. In the parasitoid wasp, Asobara tabida,
      Wolbachia is necessary for oogenesis completion, and aposymbiotic females are
      unable to produce viable offspring. The absence of egg production is also
      associated with an increase in programmed cell death in the ovaries of
      aposymbiotic females, suggesting that a mechanism that ensures the maintenance of
      Wolbachia in the wasp could also be responsible for this dependence. In order to
      decipher the general mechanisms underlying host-Wolbachia interactions and the
      origin of the dependence, we developed transcriptomic approaches to compare gene
      expression in symbiotic and aposymbiotic individuals. RESULTS: As no genetic data
      were available on A. tabida, we constructed several Expressed Sequence Tags (EST)
      libraries, and obtained 12,551 unigenes from this species. Gene expression was
      compared between symbiotic and aposymbiotic ovaries through in silico analysis
      and in vitro subtraction (SSH). As pleiotropic functions involved in immunity and
      development could play a major role in the establishment of dependence, the
      expression of genes involved in oogenesis, programmed cell death (PCD) and
      immunity (broad sense) was analyzed by quantitative RT-PCR. We showed that
      Wolbachia might interfere with these numerous biological processes, in particular
      some related to oxidative stress regulation. We also showed that Wolbachia may
      interact with immune gene expression to ensure its persistence within the host.
      CONCLUSIONS: This study allowed us to constitute the first major dataset of the
      transcriptome of A. tabida, a species that is a model system for both
      host/Wolbachia and host/parasitoid interactions. More specifically, our results
      highlighted that symbiont infection may interfere with numerous pivotal processes
      at the individual level, suggesting that the impact of Wolbachia should also be
      investigated beyond reproductive manipulations.

PMID- 22376155
TI  - Dental findings and oral health status in patients with mucopolysaccharidosis: a
      case series.
AB  - OBJECTIVE: To present a mucopolysaccharidosis (MPS) case series evaluating oral
      manifestations (clinical and radiographic), oral health status and discussing its
      implications. PATIENTS AND METHODS: All patients with MPS attending the Genetics
      clinic/Brazil were evaluated by means of anamnesis, clinical and radiographic
      examinations. RESULTS: The final sample consisted of 12 subjects (nine males and
      three females), with ages ranging from 3-31 years old. Concerning oral health, it
      was observed high levels of caries and periodontal problems. About oral
      manifestations, this study clinically observed more cases of delayed tooth
      eruption, thickness of alveolar process and thick lips. Radiographically, it was
      observed alterations on condyle, mandibular ramus and joint fossa. CONCLUSION:
      The dental changes in MPS population are high and consequently it is important to
      know them for differential diagnoses, early treatment intervention, prevention
      and education of both patients and parents/caregivers about oral health.

PMID- 22376156
TI  - Quantum-mechanical study on the mechanism of peptide bond formation in the
      ribosome.
AB  - Ribosomes transform the genetic information encoded within genes into proteins.
      In recent years, there has been much progress in the study of this complex
      molecular machine, but the mechanism of peptide bond formation and the origin of
      the catalytic power of this ancient enzymatic system are still an unsolved
      puzzle. A quantum-mechanical study of different possible mechanisms of peptide
      synthesis in the ribosome has been carried out using the M06-2X density
      functional. The uncatalyzed processes in solution have been treated with the SMD
      solvation model. Concerted and two-step mechanisms have been explored. Three main
      points suggested in this work deserve to be deeply analyzed. First, no
      zwitterionic intermediates are found when the process takes place in the
      ribosome. Second, the proton shuttle mechanism is suggested to be efficient only
      through the participation of the A2451 2'-OH and two crystallographic water
      molecules. Finally, the mechanisms in solution and in the ribosome are very
      different, and this difference may help us to understand the origin of the
      efficient catalytic role played by the ribosome.

PMID- 22376157
TI  - Effect of the cooling rate on dimerization of C60(*-) in fullerene salt
      (DMI+)2.(C60(*-)).{Cd(Et2NCS2)2I-}.
AB  - The salt (DMI(+))(2).(C(60)(*-)).{Cd(Et(2)NCS(2))(2)I(-)} (1) containing
      fullerene radical anions, the anions of cadmium diethyldithiocarbamate iodide,
      and N,N'-dimethylimidazolium cations was obtained. Fullerenes are monomeric in 1
      at 250 K and form three-dimensional packing in which each fullerene has nearly
      tetrahedral surroundings from neighboring fullerenes. Fullerenes with a shorter
      interfullerene center-to-center distance of 10.031(2) A form spiral chains
      arranged along the lattice c axis. The convolution consists of four fullerene
      molecules. Dimerization realized in 1 within the spiral chains below 135 K
      manifests a strong dependence on the cooling rate. The "frozen" monomeric phase
      was obtained upon instant quenching of 1. This phase is stable below 95 K for a
      long time but slowly converted to the dimeric phase at T > 95 K. It exhibits a
      weak antiferromagnetic interaction of spins below 95 K (the Weiss temperature is 
      4 K), which results in the splitting of the electron paramagnetic resonance (EPR)
      signal into two components below 10 K. A disordered phase containing both C(60)(*
      ) monomers and singly bonded (C(60)(-))(2) dimers with approximately 0.5/0.5
      occupancies is formed at an intermediate cooling rate (for 20 min). The position
      of each fullerene in this phase is split into three positions slightly shifted
      relative to each other. The central position corresponds to nonbonded fullerenes
      with interfullerene center-to-center distances of 9.94-10.00 A. Two other
      positions are coincided to dimeric fullerenes formed with the right and left
      fullerene neighbors within the spiral chain. This intermediate phase is
      paramagnetic with nearly zero Weiss temperature due to isolation of C(60)(*-) by
      diamagnetic species and exhibits a strongly asymmetric EPR signal below 20 K. A
      diamagnetic phase containing ordered singly bonded (C(60)(-))(2) dimers can be
      obtained only upon slow cooling of the crystal for 6 h.

PMID- 22376158
TI  - Selection of deep brain stimulation candidates in private neurology practices:
      referral may be simpler than a computerized triage system.
AB  - OBJECTIVE: The objective of this study is to compare a computerized deep brain
      stimulation (DBS) screening module (Comparing Private Practice vs. Academic
      Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX,
      USA) with traditional triage by a movement disorders specialized neurologist as
      the gold standard. METHODS: The COMPRESS consists of a combination of the Florida
      Surgical Questionnaire for Parkinson disease (FLASQ-PD), a cognitive assessment
      battery provided by MindStreams(r) (NeuroTrax Corp.), and the Geriatric
      Depression Scale and the Zung Anxiety Self-Assessment Scale. COMPRESS resulted in
      the classification of patients into three categories: "optimal
      candidate,""probable candidate," and "not a good candidate." Similar categorical
      ratings made by a referring private practice neurologist and by a trained
      movement disorders specialist were compared with the ratings generated by
      COMPRESS. RESULTS: A total of 19 subjects with Parkinson's disease were enrolled
      from five private neurological practices. The clinical impressions of the private
      practice neurologist vs. those of the movement disorders specialist were in
      agreement approximately half the time (10/19 cases). The movement disorders
      specialist and COMPRESS agreed on 15/19 cases. A further comparison between
      outcomes from the entire COMPRESS module and the FLASQ-PD questionnaire by itself
      resulted in high agreement (18/19 cases in agreement). CONCLUSIONS: The COMPRESS
      agreed with an in-person evaluation by a movement disorders neurologist
      approximately 80% of the time. The computerized COMPRESS did not provide any
      screening advantage over the short FLASQ-PD paper questionnaire. Larger studies
      will be needed to assess the utility and cost effectiveness of this computerized
      triage method for DBS.

PMID- 22376159
TI  - Impact of a hospital improvement initiative in Bangladesh on patient experiences
      and satisfaction with services: two cross-sectional studies.
AB  - BACKGROUND: The Bangladesh government implemented a pilot Hospital Improvement
      Initiative (HII) in five hospitals in Sylhet division between 1998 and 2003. This
      included management and behaviour change training for staff, waste disposal and
      procurement, and referral arrangements. Two linked cross-sectional surveys in
      2000 and 2003 assessed the impact of the HII, assessing both patients' experience
      and satisfaction and public views and use of the hospitals. METHODS: In each
      survey we asked 300 consecutive outpatients and a stratified random sample of 300
      inpatients in the five hospitals about waiting and consultation time, use of an
      agent for admission, and satisfaction with privacy, cleanliness, and staff
      behaviour. The field teams observed cleanliness and privacy arrangements, and
      visited a sample of households in communities near the hospitals to ask about
      their opinions and use of the hospital services. Analysis examined changes over
      time in patients' experience and views. Multivariate analysis took account of
      other variables potentially associated with the outcomes. Survey managers
      discussed the survey findings with gender stratified focus groups in each sample
      community. RESULTS: Compared with 2000, an outpatient in three of the hospitals
      in 2003 was more likely to be seen within 10 minutes and for at least five
      minutes by the doctor, but outpatients were less likely to report receiving all
      the prescribed medicines from the hospital. In 2003, inpatients were more likely
      to have secured admission without using an agent. Although patients' satisfaction
      with several aspects of care improved, most changes were not statistically
      significant. Households in 2003 were significantly more likely to rate the
      hospitals as good than in 2000. Use of the hospitals did not change, except that
      more households used the medical college hospital for inpatient care in 2003.
      Focus groups confirmed criticisms of services and suggested improvements.
      CONCLUSION: Improvements in some aspects of patients' experience may have been
      due to the programme, but the decreased availability of medicines in government
      facilities across the country over the period also occurred in these hospitals.
      Monitoring patients' experience and satisfaction as well as public views and use
      of hospital services is feasible and useful for assessing service interventions.

PMID- 22376160
TI  - Signal transducer and activator of transcription 3 (STAT3) gene polymorphisms are
      associated with treatment outcomes in acute myeloid leukemia.
AB  - INTRODUCTION: In the Janus kinase/signal transducer and activator of
      transcription (JAK/STAT) signaling pathway, STAT3 is one of the most prominent
      prognosis factors for cancer and leukemia. STAT3 activation might promote
      cellular transformation and therefore have an important role in human tumors.
      This study aimed to investigate the relationship between STAT3 polymorphisms and
      treatment response of acute myeloid leukemia (AML) in the Chinese population.
      METHODS: Three single-nucleotide polymorphisms (SNPs) were tested in 130 patients
      with AML. Genomic DNA was isolated from peripheral blood and assayed by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). RESULTS: The results of response to chemotherapy showed that there were
      strong relationships between unfavorable cytogenetics, partial remission (and
      even no remission), and GG genotype frequency in rs9909659 (P = 0.01 and 0.03).
      Patients younger than 45 years were associated significantly with GA/AA genotype
      (P = 0.01). CONCLUSIONS: The results of this study suggest that the GG genotype
      in rs9909659 might confer increased resistance to standard chemotherapy.

PMID- 22376162
TI  - Endorsement of sexist ideology in Taiwan and the United States: social dominance
      orientation, right-wing authoritarianism, and deferential family norms.
AB  - Despite close relationships between men and women in daily lives, gender
      inequality is ubiquitous and often supported by sexist ideology. The
      understanding of potential bases of sexist ideology is thus important. According
      to Duckitt's dual-process model (2001), different worldviews may explain
      different types of sexist ideology. Individuals who hold a "competitive world"
      worldview tend to endorse group-based dominance. This lends itself to the
      endorsement of hostile sexism, because hostile sexism is an obvious form of male
      dominance. Conversely, individuals who hold a "dangerous world" worldview tend to
      adhere to social cohesion, collective security, and social traditions. This lends
      itself to the endorsement of benevolent sexism, because benevolent sexism values
      women who conform to gender norms. As predicted by Duckitt's model, research has
      shown that social dominance orientation, a general orientation towards the
      endorsement of group-based dominance, is closely associated with hostile sexism.
      Furthermore, right-wing authoritarianism, which measures adherence to social
      traditions, is closely associated with benevolent sexism. Due to the
      interdependent nature of gender relationships, the current research proposed that
      a relationship-based belief in hierarchy, deferential family norms, and norms
      depicting proper manners among family members should predict the endorsement of
      hostile and benevolent sexism, after controlling for social dominance orientation
      and right-wing authoritarianism. As predicted, according to student samples
      collected in Taiwan and the US, the endorsement of deferential family norms
      predicted the endorsement of hostile sexism and of benevolent sexism,
      respectively. In addition, among men and women, social dominance orientation
      predicted hostile sexism more strongly (as opposed to benevolent sexism), whereas
      right-wing authoritarianism predicted benevolent sexism more strongly (as opposed
      to hostile sexism). Implications regarding relationship norms, social dominance
      orientation, right-wing authoritarianism, and sexist ideology are discussed. 

PMID- 22376163
TI  - The use and safety of combined resistance and aerobic training in a patient with
      complications related to type 2 diabetes: a case report.
AB  - PURPOSE: No guidelines for tailoring exercise programs for patients with diabetic
      complications are available. The purpose of this case report is to report our
      experiences with a tailored exercise program including safety precautions for a
      patient with complications related to type 2 diabetes and exercise related
      regulation issues. CASE DESCRIPTION: A patient with multiple diabetic
      complications, poor glycemic control, and a history of foot ulceration
      participated in a 12-week exercise program with multiple safety precautions.
      OUTCOMES: Hypoglycemic events required adjustments in training intensity and
      insulin dosage. Periodic foot screening revealed no ulceration. Target training
      intensity was achieved at the end of the program, although exercise load could
      not be increased according to the planned protocol. Training effects were
      observed in muscle strength increased, perceived limitations in daily functioning
      diminished and no change in sub maximal exercise capacity. CONCLUSION: This
      patient with severe diabetic complications participated safely and successfully
      in an exercise program. Problems with glycemic control occurred but did not
      preclude adherence to incremental exercise. We recommend a medical screening, the
      availability of a network of specialists, and a physical therapist with
      sufficient knowledge of diabetic complications and exercise physiology to guide
      training in this patient population. [ IMPLICATIONS FOR REHABILITATION: * This
      case report demonstrates that physical functioning can be improved safely in a
      patient with multiple diabetic complications.* For safety precautions, a medical
      screening including a X-ECG and a foot screen prior to exercise, and the
      involvement of a diabetes specialist nurse, a podiatrist, an endocrinologist and
      a physiatrist in the rehabilitation team are recommended.* Sufficient knowledge
      of diabetic complications and exercise physiology is needed in supervising
      exercise programs for patients with multiple diabetic complications.]

PMID- 22376164
TI  - Synthesis and assembly of functional high molecular weight adiponectin multimers
      in an engineered strain of Escherichia coli.
AB  - Adiponectin has many beneficial effects on cardiovascular and obesity-related
      disorders. It is part of a class of proteins that contains short collagenous
      domains, along with surfactant proteins A and D, and complement protein C1q. This
      class of biomacromolecules requires post-translational modifications to form
      biologically active assemblies. By introducing a set of post-translational
      modifying enzymes into  Escherichia coli , we have created a prokaryotic
      expression system that functionally assembles adiponectin, as assessed by the
      ability of produced adiponectin multimers to suppress human endothelial cell
      apoptosis. This study represents the first example of the assembly of functional
      high order multimers of any member of this class of proteins outside of
      eukaryotic cells. Furthermore, the results give fundamental insight into the
      process of assembly such as the necessity and sufficiency of various post
      translational steps for functional assembly. We expect that fine-tuning of the
      expression system will allow for efficient production and functional assembly of
      biomolecules that assemble via short collagenous domains.

PMID- 22376165
TI  - Overall increasing incidence of nonmelanoma skin cancer.

PMID- 22376166
TI  - Cardiovascular, ocular and bone adverse reactions associated with
      thiazolidinediones: a disproportionality analysis of the US FDA adverse event
      reporting system database.
AB  - BACKGROUND: : The risk of myocardial infarction, macular oedema and bone
      fractures associated with thiazolidinediones (TZDs) has been extensively
      investigated. OBJECTIVE: : The aim of the study was to verify if the analysis of
      a large spontaneous reporting database could generate early signals on these
      adverse drug reactions (ADRs) associated with TZDs. METHODS: : A case/non-case
      study, restricted to antidiabetic drugs, was performed on spontaneous reports of
      ADRs (2005-2008) in the US FDA Adverse Event Reporting System (AERS). The method
      was applied to TZDs, both as a drug class and as single agents. The reporting
      odds ratio (ROR) with 95% CI was calculated as a measure of disproportionality in
      the whole dataset and in a quarter-by-quarter analysis. RESULTS: : TZD use was
      registered in 49 589 out of 301 950 drug-reaction pairs (16%), with significant
      disproportionality for myocardial infarction (ROR 4.71; 95% CI 4.40, 5.05),
      macular oedema (3.88; 2.79, 5.39) and bone fractures (1.73; 1.53, 1.96). Separate
      analysis of the two TZDs showed that only rosiglitazone was associated with
      myocardial infarction (7.86; 7.34, 8.34) and macular oedema (5.55; 3.94, 7.79),
      whereas pioglitazone was associated with multiple site fractures (2.00; 1.70,
      2.35), in particular upper and lower limb and pelvic fractures. The quarter-by
      quarter analysis identified disproportionality for myocardial infarction (3.13;
      2.38, 4.10) and bone fractures since January-March 2005 (2.70; 1.04, 2.78).
      CONCLUSIONS: : The frequency of reporting of myocardial infarction, macular
      oedema and fractures was significantly higher for TZDs in comparison with other
      antidiabetic drugs, with large intraclass differences. Both myocardial infarction
      and bone fracture signals appeared before major publications on these safety
      issues.

PMID- 22376167
TI  - The BRAF V600E mutation in papillary thyroid carcinoma is associated with glucose
      transporter 1 overexpression.
AB  - BACKGROUND: The glucose transporter 1 (GLUT1) is a key protein that facilitates
      the extensive glucose uptake of cancer cells, and its overexpression is
      associated with more aggressive tumor phenotypes. In cases of BRAF mutations,
      GLUT1 seems to be a target of the constitutive activation of the RAF/MEK/ERK
      pathway. In this study, we hypothesized that the common BRAF V600E mutation was
      associated with GLUT1 overexpression and proliferation in papillary thyroid
      carcinomas (PTCs). METHODS: A total of 57 cases of paraffin-embedded PTC (31 BRAF
      V600E, 26 wild-type BRAF) were investigated using immunohistochemistry with
      antibodies against GLUT1 and Ki-67 (MK167) protein. The BRAF V600E mutations were
      detected using direct sequencing of genomic DNA that was isolated from formalin
      fixed paraffin-embedded tumor tissues. GLUT1 expression was assessed using the
      Remmele immunoreactive score and subdivided into three groups (I=negative,
      II=weakly positive, and III=positive). The Ki-67 labeling index (Ki-67 LI) was
      determined by counting Ki-67-positive nuclei. RESULTS: GLUT1 expression was found
      in 39/57 (68.4%) samples of PTC. The occurrence of the BRAF V600E genetic variant
      was significantly correlated with GLUT1 overexpression (p=0.007) and showed a
      trend toward higher proliferation, which was indicated by Ki-67 LI (p=0.06).
      Moreover, GLUT1 overexpression was positively associated with Ki-67 labeling
      (p=0.023). CONCLUSIONS: The V600E BRAF mutation in PTC may contribute to the
      initiation of the glycolytic phenotype and confers growth advantages in cancer
      cells. Better understanding of the molecular mechanisms of cancer cell energy
      metabolism may lead to the implementation of targeted treatment modalities, which
      regulate cancer glucose uptake.

PMID- 22376168
TI  - Isolated cardiac metastasis from papillary thyroid cancer: prolonged survival
      with late diagnosis related to inadequate positron emission tomography
      preparation.

PMID- 22376169
TI  - Thyroid Hurthle cell carcinoma metastatic to the pituitary gland.

PMID- 22376172
TI  - Glycosylated hemoglobin and outcomes in diabetic patients with acute myocardial
      infarction after successful revascularization with stent placement: findings from
      the guthrie health off-label stent (GHOST) investigators.
AB  - OBJECTIVE: We evaluated the influence of glycemic control on cardiovascular
      outcomes in diabetic patients with acute myocardial infarction (AMI) who
      underwent successful percutaneous coronary intervention (PCI) with stent
      placement. BACKGROUND: In patients presenting with AMI, diabetic status confers
      adverse cardiovascular outcomes after PCI. However, the influence of glycemic
      control on outcomes after successful PCI is less well studied. METHODS: We
      examined 231 consecutive diabetes mellitus (DM) patients with AMI who underwent
      successful primary PCI and had evaluation of glycosylated hemoglobin (HbA1c) from
      30 days before to 90 days after AMI. Patients were categorized in 2 groups,
      controlled DM with HbA1c <= 7.0 (N = 83, 36%) and uncontrolled DM with HbA1c >
      7.0 (N = 148, 64%). We assessed 12-month cardiovascular outcomes in study groups.
      RESULTS: Uncontrolled diabetics were younger, tended to be less hypertensive, and
      had higher baseline glomerular filtration rate and final vessel diameter compared
      to controlled diabetics. Uncontrolled DM patients had similar major adverse
      cardiovascular events (MACE; composite of all-cause death, MI, target vessel
      revascularization [TVR], and stent thrombosis [ST]; 20% vs. 30%, log-rank P =
      0.54), death (8.8% vs. 12%, P = 0.40), MI (8.8% vs. 9.6%, P = 0.76), TVR (9.5%
      vs. 8.4%, P = 0.95), and ST (3.4% vs. 4.8%, P = 0.54) as the controlled
      diabetics. In Cox regression analysis, after adjustment for baseline differences,
      glycemic control had no independent influence on study outcomes. CONCLUSION:
      Glycemic control, determined by HbA1c, does not seem to influence cardiovascular
      outcomes in diabetic patients with AMI after successful stent placement.

PMID- 22376171
TI  - Condom use within non-commercial partnerships of female sex workers in southern
      India.
AB  - BACKGROUND: Although female sex workers (FSWs) report high levels of condom use
      with commercial sex clients, particularly after targeted HIV preventive
      interventions have been implemented, condom use is often low with non-commercial
      partners. There is limited understanding regarding the factors that influence
      condom use with FSWs' non-commercial partners, and of how programs can be
      designed to increase condom use with these partners. The main objectives of this
      study were therefore to describe FSWs' self-reported non-commercial partners,
      along with interpersonal factors characterizing their non-commercial
      partnerships, and to examine the factors associated with consistent condom use
      (CCU) within non-commercial partnerships. METHODS: This study used data collected
      from cross-sectional questionnaires administered to 988 FSWs in four districts in
      Karnataka state in 2006-07. We used bivariate and multivariable logistic
      regression analysis to examine the relationship between CCU (i.e., 'always'
      compared to 'never', 'sometimes' or 'frequently') with non-commercial partners of
      FSWs (including the respondents' husband or main cohabiting partner [if not
      married] and their most recent non-paying partner [who is neither a husband nor
      the main cohabiting partner, and with whom the FSW had sex within the previous
      year]) and interpersonal factors describing these partnerships, as well as social
      and environmental factors. Weighting and survey methods were used to account for
      the cluster sampling design. RESULTS: Overall, 511 (51.8%) FSWs reported having a
      husband or cohabiting partner and 247 (23.7%) reported having a non-paying
      partner. CCU with these partners was low (22.6% and 40.3% respectively). In
      multivariable analysis, the odds of CCU with FSWs' husband or cohabiting partner
      were 1.8-fold higher for FSWs whose partner knew she was a sex worker (adjusted
      odds ratio [AOR]: 1.84, 95% confidence intervals[CI]: 1.02-3.32) and almost 6
      fold higher if the FSW was unmarried (AOR: 5.73, 95%CI: 2.79-11.76]. CCU with
      FSWs' non-paying partner decreased by 18% for each one-year increase in the
      duration of the relationship (AOR: 0.82, 95%CI: 0.68-0.97). CONCLUSIONS: This
      study revealed important patterns and interpersonal determinants of condom use
      within non-commercial partnerships of FSWs. Integrated structural and community
      driven HIV/STI prevention programs that focus on gender and reduce sex work
      stigma should be investigated to increase condom use in non-commercial
      partnerships.

PMID- 22376174
TI  - 10-year follow-up of immediately loaded implants with TiUnite porous anodized
      surface.
AB  - BACKGROUND: The immediate loading of implants with a porous anodized surface is a
      well-described technique. Few data are however available on the long-term
      outcomes. PURPOSE: The aim of this prospective study was to assess the 10-year
      performance of TiUnite implants supporting fixed prostheses placed with an
      immediate loading approach in both postextractive and healed sites. MATERIALS AND
      METHODS: All patients received a fixed provisional restoration supported by
      immediately loaded parallel design, self-tapping implants with a porous anodized
      TiUnite surface, and an external-hexagonal connection. Both healed and
      postextractive cases were included. Success and survival rate for restorations
      and implants, changes in marginal peri-implant bone level, probing depth
      measurements, biological or technical complications, and any other adverse event
      were recorded at yearly follow-up up to 10 years after surgery. RESULTS: A total
      of 210 implants fulfilled the inclusion criteria and were consecutively placed in
      59 patients. Forty-seven (22.38%) implants were lost because of the recalled
      patient refused to attend the planned 10-year follow-up. Five over 210 (2.38%)
      implants were lost. At the final follow-up, the accumulated mean marginal bone
      loss and probing depth were, respectively, 1.93 mm (SD 0.40) and 2.54 mm (SD
      0.44) for the implants placed in healed sites (n = 84); 1.98 mm (SD 0.37) and
      2.63 mm (SD 0.39) for the implants placed in postextractive sites (n = 74). The
      restorations examined achieved a cumulative 65.26% success rate and 97.96%
      survival rate. The implants placed in healed and postextractive sites,
      respectively, achieved a 98.05% and a 96.52% cumulative survival rate.
      CONCLUSIONS: Positive results in terms of bone maintenance in the long-term
      perspective are to be expected using immediately loaded implants with a TiUnite
      porous anodized surface in both postextractive and healed sites when adequate
      levels of oral hygiene are kept.

PMID- 22376175
TI  - Rapamycin inhibition of baculovirus recombinant (BVr) ribosomal protein S6 kinase
      (S6K1) is mediated by an event other than phosphorylation.
AB  - BACKGROUND: Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved
      kinase that is activated in response to growth factors and viral stimuli to
      influence cellular growth and proliferation. This downstream effector of target
      of rapamycin (TOR) signaling cascade is known to be directly activated by TOR-
      kinase mediated hydrophobic motif (HM) phosphorylation  at Threonine 412 (T412).
      Selective loss of this phosphorylation by inactivation of TOR kinase or
      activation/recruitment of a phosphatase has accordingly been implicated in
      mediating inhibition by rapamycin. FINDINGS: We present evidence that baculovirus
      driven expression of S6K1 in insect cells (Sf9) fails to activate the enzyme and
      instead renders it modestly active representing 4-6 folds less activity than its
      fully active mammalian counterpart. Contrary to the contention that viral
      infection activates TOR signaling pathway, we report that BVr enzyme fails to
      exhibit putative TOR dependent phosphorylation at the HM and the resultant
      phosphorylation at the activation loop (AL) of the enzyme, correlating with the
      level of activity observed. Surprisingly, the BVr enzyme continued to exhibit
      sensitivity to rapamycin that remained unaffected by mutations compromised for
      TOR phosphorylation (T412A) or deletions compromised for TOR binding (DeltaNH 2
      46/DeltaCT104). CONCLUSIONS: These data together with the ability of the BVr
      enzyme to resist inactivation by phosphatases indicate that inhibition by
      rapamycin is not mediated by any phosphorylation event in general and TOR
      dependent phosphorylation in particular.

PMID- 22376176
TI  - Bifunctionalized amphilectane diterpenes from the sponge Stylissa cf. massa.
AB  - Two new amphilectane-type diterpenes, 8-isocyanato-15-formamidoamphilect-11(20)
      ene (1) and 8-isothiocyanato-15-formamidoamphilect-11(20)-ene (2), along with two
      known derivatives, 8-isocyano-15-formamidoamphilect-11(20)-ene (3) and 7
      formamidoamphilect-11(20),15-diene (4), were isolated from the sponge Stylissa
      cf. massa. Diterpenes bearing two different isonitrile-related functionalities,
      as in 1-3, are rare. The coexistence of these compounds, all of which possess the
      identical carbon skeleton, in the same sponge specimen suggests interconversion
      among them. All the isolated compounds were tested for antimalarial activity.
      Compound 3 proved approximately 10 times more active than 1 and 2, indicating the
      importance of the isonitrile moiety to antimalarial activity versus the
      isocyanate and isothiocyanate groups, respectively. Compound 4, which contains
      only the formamide group, was inactive at the highest concentration tested.

PMID- 22376178
TI  - Framing rights and responsibilities: accounts of women with a history of AIDS
      activism.
AB  - BACKGROUND: In South Africa, policy with respect to HIV/AIDS has had a strong
      rights-based framing in line with international trends and in keeping with the
      constitutional overhaul in the post-Apartheid era. There have also been
      considerable advances since 1994 towards legal enshrinement of sexual and
      reproductive health rights and in the provision of related services. Since HIV in
      this setting has heavily affected women of reproductive age, there has been
      discussion about the particular needs of this subgroup, especially in the context
      of service integration. This paper is concerned with the way in which HIV
      positive women conceptualise these rights and whether they wish and are able to
      actualise them in their daily lives. METHODS: In 2003 a group of women involved
      with the Treatment Action Campaign and Medicines Sans Frontieres participated in
      an initiative to 'map' their bodies as affected by the virus. A book containing
      the maps and narratives was published and used as a political tool to pressure
      the government of the day to roll out antiretroviral therapy (ART) to the
      population. In 2008, the authors coordinated an initiative that involved
      conducting follow-up in-depth interviews in which five of these women reflected
      on those body maps and on how their lives had changed in the intervening five
      years since gaining the right to treatment through the public sector. RESULTS:
      Drawing upon this qualitative data and published sources, these new accounts are
      analysed in order to reflect the perspectives of these women living with chronic
      HIV with respect to their sexual relations and fertility desires. The paper
      reveals difficulties faced by these women in negotiating sexual relationships and
      disclosure of their HIV positive status. It focuses on how they perceive relative
      responsibilities in terms of taking preventative measures in sexual encounters.
      Women adopt tactics within a context characterised by various inequalities in
      order to 'make do', such as by remaining silent about their status. Concerns
      about childbearing can be addressed by information and support from a health care
      worker. CONCLUSIONS: Women's experience of HIV as a chronic illness and the need
      to adhere to ART, is linked to the way in which the language of responsibility
      can come to counter-balance a language of rights in treatment programmes.

PMID- 22376177
TI  - Male-killing Wolbachia do not protect Drosophila bifasciata against viral
      infection.
AB  - BACKGROUND: Insect symbionts employ multiple strategies to enhance their spread
      through populations, and some play a dual role as both a mutualist and a
      reproductive manipulator. It has recently been found that this is the case for
      some strains of Wolbachia, which both cause cytoplasmic incompatibility and
      protect their hosts against viruses. Here, we carry out the first test as to
      whether a male-killing strain of Wolbachia also provides a direct benefit to its
      host by providing antiviral protection to its host Drosophila bifasciata. We
      infected flies with two positive sense RNA viruses known to replicate in a range
      of Drosophila species (Drosophila C virus and Flock House virus) and measure the
      rate of death in Wolbachia positive and negative host lines with the same genetic
      background. RESULTS: Both viruses caused considerable mortality to D. bifasciata
      flies, with Drosophila C virus killing 43% more flies than the uninfected
      controls and Flock House virus killing 78% more flies than the uninfected
      controls. However, viral induced mortality was unaffected by the presence of
      Wolbachia. CONCLUSION: In the first male-killing Wolbachia strain tested for
      antiviral effects, we found no evidence that it conferred protection against two
      RNA viruses. We show that although antiviral resistance is widespread across the
      Wolbachia phylogeny, the trait seems to have been lost or gained along some
      lineages. We discuss the potential mechanisms of this, and can seemingly discount
      protection against these viruses as a reason why this symbiont has spread through
      Drosophila populations.

PMID- 22376179
TI  - Copper ion mediated selective cleavage of C-S bond in ferrocenylthiosemicarbazone
      forming mixed geometrical [(PPh3)Cu(MU-S)2Cu(PPh3)2] having Cu2S2 core: toward a
      new avenue in copper-sulfur chemistry.
AB  - Unprecedented selective cleavage of the carbon-sulfur bond of the
      ferrocenylthiosemicarbazone moiety has been observed for the first time,
      resulting in the formation of mixed geometrical binuclear copper complex
      [(PPh(3))Cu(MU-S)(2)Cu(PPh(3))(2)]. Upon trying direct synthesis of the title
      complex, an unusual tetranuclear [Cu(4)(MU(3)-Cl)(4)(PPh(3))(4)] cubane resulted.

PMID- 22376180
TI  - Filter diagonalization method-based mass spectrometry for molecular and
      macromolecular structure analysis.
AB  - Molecular and macromolecular structure analysis by high resolution and accurate
      mass spectrometry (MS) is indispensable for a number of fundamental and applied
      research areas, including health and energy domains. Comprehensive structure
      analysis of molecules and macromolecules present in the extremely complex samples
      and performed under time-constrained experimental conditions demands a
      substantial increase in the acquisition speed of high resolution MS data. We
      demonstrate here that signal processing based on the filter diagonalization
      method (FDM) provides the required resolution for shorter experimental transient
      signals in ion cyclotron resonance (ICR) MS compared to the Fourier transform
      (FT) processing. We thus present the development of a FDM-based MS (FDM MS) and
      demonstrate its implementation in ICR MS. The considered FDM MS applications are
      in bottom-up and top-down proteomics, metabolomics, and petroleomics.

PMID- 22376181
TI  - The effects of temporary spinal cord stimulation (or spinal nerve root
      stimulation) on the management of early postherpetic neuralgia from one to six
      months of its onset.
AB  - OBJECTIVE: We examined the efficacy of temporary spinal cord stimulation
      involving the insertion of only a needle and quadripolar lead into the epidural
      space and applied using an extracorporeal stimulation generator for a few weeks
      of early postherpetic neuralgia from one to six months of its onset. MATERIALS
      AND METHODS: Temporary spinal cord stimulation was applied in 33 patients with
      postherpetic neuralgia and in whom epidural block was effective. Temporary spinal
      cord stimulation was applied over seven days, and analgesic effects was evaluated
      based on visual analog scale (VAS) values before and after one, three, and six
      months following treatment. An analgesic effect was defined as a decrease of over
      50% in the VAS value compared with before treatment. RESULTS: VAS values
      decreased significantly from 68.1 mm (standard deviation [SD]+/- 15.2) before
      treatment to 37.5 mm (SD +/- 20.4) after one month, to 38.0 mm (SD +/- 18.7)
      after three months, and to 35.0 mm (SD +/- 21.3) after six months. In 21/33
      (63.6%) cases, an analgesic effect, defined as a decrease in the VAS value of
      greater than 50%, was observed one month after treatment, in 20/33 (60.6%) cases
      such an effect was observed three months after treatment, and in 21/33 (63.6%)
      cases the effect was still observed six months after treatment. CONCLUSIONS:
      Temporary spinal cord stimulation is an effective analgesic method for early
      postherpetic neuralgia from one to six months of its onset.

PMID- 22376183
TI  - Enhanced stability of polymeric micelles based on postfunctionalized
      poly(ethylene glycol)-b-poly(gamma-propargyl L-glutamate): the substituent
      effect.
AB  - One of the major obstacles that delay the clinical translation of polymeric
      micelle drug delivery systems is whether these self-assembled micelles can retain
      their integrity in blood following intravenous (IV) injection. The objective of
      this study was to evaluate the impact of core functionalization on the
      thermodynamic and kinetic stability of polymeric micelles. The combination of
      ring-opening polymerization of N-carboxyanhydride (NCA) with highly efficient
      "click" coupling has enabled easy and quick access to a family of poly(ethylene
      glycol)-block-poly(gamma-R-glutamate)s with exactly the same block lengths, for
      which the substituent "R" is tuned. The structures of these copolymers were
      carefully characterized by (1)H NMR, FT-IR, and GPC. When pyrene is used as the
      fluorescence probe, the critical micelle concentrations (CMCs) of these polymers
      were found to be in the range of 10(-7)-10(-6) M, which indicates good
      thermodynamic stability for the self-assembled micelles. The incorporation of
      polar side groups in the micelle core leads to high CMC values; however, micelles
      prepared from these copolymers are kinetically more stable in the presence of
      serum and upon SDS disturbance. It was also observed that these polymers could
      effectively encapsulate paclitaxel (PTX) as a model anticancer drug, and the
      micelles possessing better kinetic stability showed better suppression of the
      initial "burst" release and exhibited more sustained release of PTX. These PTX
      loaded micelles exerted comparable cytotoxicity against HeLa cells as the
      clinically approved Cremophor PTX formulation, while the block copolymers showed
      much lower toxicity compared to the cremophor-ethanol mixture. The present work
      demonstrated that the PEG-b-PPLG can be a uniform block copolymer platform toward
      development of polymeric micelle delivery systems for different drugs through the
      facile modification of the PPLG block.

PMID- 22376184
TI  - Changes in HIV knowledge, and socio-cultural and sexual attitudes in South India
      from 2003-2009.
AB  - BACKGROUND: As communities face serious pressures on traditional values, such as
      those posed by HIV infection, cultural inertia may result, whereby existing
      trends towards more liberalized views of sexuality are stalled. We examined
      changes in attitudes around HIV in Bagalkot district, south India, between 2003
      and 2009. METHODS: General population surveys were conducted in 2003 and 2009,
      among approximately 6,600 randomly sampled men and women in 10 villages and 20
      urban blocks of Bagalkot. Questions about HIV knowledge, sexuality, gender and
      condoms were included. We compared responses in the two surveys using a
      multivariate logistic regression model. RESULTS: Awareness of HIV increased
      significantly from 76.9% in 2003 to 87.8% in 2009, and condom awareness increased
      significantly (37.4% to 65.4%) in all groups studied. However, in 2009, only 23%
      of people mentioned condoms as a means of prevention, an improvement from 8% in
      2003 (adjusted odds ratio (AOR) 3.3; 95%CI 2.6-4.1, p <0.001). There was a
      significant increase in the number of women believing sex workers should be
      compulsorily tested for HIV (76.3%-86.4%%, AOR 1.8; 95%CI 1.4-2.4, p<0.001). An
      increasing number agreed that "it is wrong to talk about sex" (p=0.05),
      especially women (21.9% vs. 32.4%, p<0.01). There was an increase in women who
      thought it "wrong to talk about AIDS in a respectable family", and more
      respondents in 2009 thought it improper to discuss condoms (15.6% vs. 27.4%, AOR
      1.9, 95%CI 1.4-2.8, p=0.001). In 2003, 31.4% agreed that "access to condoms
      promotes promiscuity", increasing to 45.2% in 2009 (AOR 1.7; 95%CI 1.3-2.3,
      p<0.001). Educated and young urban women were the most likely to believe this. In
      2003, 19.3% and in 2009 30.2% (AOR 1.8, 95%CI 1.4-2.3, p<0.001) thought that sex
      education promotes sexual activity and promiscuity. CONCLUSIONS: Despite
      increases over time in HIV-related knowledge and reductions in stigmatizing
      attitudes, resistance to changing cultural mores was apparent, with less
      willingness to embrace openness and discuss sexuality. Young and female
      respondents appeared to be the most resistant to change, reflecting a cultural
      inertia that mirrors studies of other pressures on traditional societal values.
      More effort is required to advocate among women and young people for healthy
      sexuality, openness and safe sex practices.

PMID- 22376185
TI  - Enhanced separation performance of PVDF/PVP-g-MMT nanocomposite ultrafiltration
      membrane based on the NVP-grafted polymerization modification of montmorillonite
      (MMT).
AB  - A novel hydrophilic nanocomposite additive (PVP-g-MMT), coupling of hydrophilic
      modifier, self-dispersant, and pore-forming agent (porogen), was synthesized by
      the surface modification of montmorillonite (MMT) with N-vinylpyrrolidone (NVP)
      via "grafting from" polymerization in the presence of H(2)O(2)-NH(3).H(2)O as the
      initiator, and then the nanocomposite membrane of poly(vinylidene fluoride)
      (PVDF) and PVP-g-MMT was fabricated by wet phase inversion onto clean glass
      plates. The existence and dispersion of PVP-g-MMT had a great role on structures,
      morphologies, surface composition, and chemistry of the as-prepared nanocomposite
      membranes confirmed by varieties of spectroscopic and microscopic
      characterization techniques, all of which were the correlated functions of PVP-g
      MMT content in casting solution. By using the dead-end filtration of protein
      aqueous solution, the performance of the membrane was evaluated. It was seen that
      all of the nanocomposite membranes showed obvious improvement of water flux and
      proper BSA rejection ratio, compared to the control PVDF membrane. Meanwhile,
      dynamic BSA fouling resistance and flux recovery properties were also greatly
      enhanced due to the changes of surface hydrophilicity and morphologies. All the
      experimental results indicated that the as-prepared PVDF nanocomposite membranes
      showed better separation performances than the control PVDF membrane. Hopefully,
      the demonstrated method of hydrophilic nanocomposite additive synthesis would be
      applied for commonly hydroxyl group-containing inorganic nanoparticles, which was
      favorable to fabricate hydrophilic nanoparticle-enhanced polymer membranes for
      water treatment.

PMID- 22376187
TI  - Protein carbonylation and aggregation precede neuronal apoptosis induced by
      partial glutathione depletion.
AB  - While the build-up of oxidized proteins within cells is believed to be toxic,
      there is currently no evidence linking protein carbonylation and cell death. In
      the present study, we show that incubation of nPC12 (neuron-like PC12) cells with
      50 MUM DEM (diethyl maleate) leads to a partial and transient depletion of
      glutathione (GSH). Concomitant with GSH disappearance there is increased
      accumulation of PCOs (protein carbonyls) and cell death (both by necrosis and
      apoptosis). Immunocytochemical studies also revealed a temporal/spatial
      relationship between carbonylation and cellular apoptosis. In addition, the
      extent of all three, PCO accumulation, protein aggregation and cell death,
      augments if oxidized proteins are not removed by proteasomal degradation.
      Furthermore, the effectiveness of the carbonyl scavengers hydralazine, histidine
      hydrazide and methoxylamine at preventing cell death identifies PCOs as the toxic
      species. Experiments using well-characterized apoptosis inhibitors place protein
      carbonylation downstream of the mitochondrial transition pore opening and
      upstream of caspase activation. While the study focused mostly on nPC12 cells,
      experiments in primary neuronal cultures yielded the same results. The findings
      are also not restricted to DEM-induced cell death, since a similar relationship
      between carbonylation and apoptosis was found in staurosporine- and buthionine
      sulfoximine-treated nPC12 cells. In sum, the above results show for the first
      time a causal relationship between carbonylation, protein aggregation and
      apoptosis of neurons undergoing oxidative damage. To the best of our knowledge,
      this is the first study to place direct (oxidative) protein carbonylation within
      the apoptotic pathway.

PMID- 22376189
TI  - Iron starvation regulates the type III secretion system in Bordetella
      bronchiseptica.
AB  - The type III secretion system (T3SS) plays a key role in the exertion of full
      virulence by Bordetella bronchiseptica. However, little is known about the
      environmental stimuli that induce expression of T3SS genes. Here, it is reported
      that iron starvation is a signal for T3SS gene expression in B. bronchiseptica.
      It was found that, when B. bronchiseptica is cultured under iron-depleted
      conditions, secretion of type III secreted proteins is greater than that in
      bacteria grown under iron-replete conditions. Furthermore, it was confirmed that
      induction of T3SS-dependent host cell cytotoxicity and hemolytic activity is
      greatly enhanced by infection with iron-depleted Bordetella. In contrast,
      production of filamentous hemagglutinin is reduced in iron-depleted Bordetella.
      Thus, B. bronchiseptica controls the expression of virulence genes in response to
      iron starvation.

PMID- 22376190
TI  - Impact of medication adherence to disease-modifying drugs on severe relapse, and
      direct and indirect costs among employees with multiple sclerosis in the US.
AB  - OBJECTIVE: To compare rates of severe relapse and total direct and indirect costs
      over a 2-year period between US-based employees with multiple sclerosis (MS) who
      were adherent and non-adherent to disease-modifying drugs (DMDs). METHODS:
      Employees with >=1 MS diagnosis (ICD-9-CM: 340.x) and >=1 DMD pharmacy claim
      between 1/1/2002-12/31/2007 were identified from a large US administrative claims
      database. Patients had continuous coverage >=6 months before (baseline) and >=24
      months after (study period) their index date (first DMD claim). Adherence was
      measured using medication possession ratio (MPR) over the study period. Patients
      with MPR >=80% were considered adherent (n = 448) and those with MPR <80% as non
      adherent (n = 200). Multivariate analyses were used to compare rates of severe
      relapse (inpatient or Emergency Department visit with MS diagnosis) and costs in
      2007 dollars between DMD adherent and non-adherent patients. Direct costs were
      calculated as reimbursements to providers for medical services and prescription
      drugs excluding DMDs. Indirect costs included disability and medically-related
      absenteeism costs. RESULTS: DMD adherent patients were on average older (43.5 vs
      41.8 years, p = 0.015) and more likely to be male (38.6% vs 26.0%, p = 0.002)
      compared with non-adherent patients. Adherent patients had lower rates of
      depression, higher rates of previous DMD use, and higher baseline MS-related
      costs. After adjusting for differences in baseline characteristics, DMD adherent
      patients had a lower rate of severe relapse (12.4% vs 19.9%, p = 0.013) and lower
      total (direct and indirect) costs ($14,095 vs $16,638, p = 0.048) over the 2-year
      study period. CONCLUSIONS: In this study, DMD adherence was associated with a
      significantly lower rate of severe relapse and lower total costs over 2 years.
      Causality cannot be inferred because adherence and outcomes were measured over
      the same period. The study was subject to limitations associated with use of
      claims data and the absence of clinical measures.

PMID- 22376191
TI  - Does contracting of health care in Afghanistan work? Public and service-users'
      perceptions and experience.
AB  - BACKGROUND: In rebuilding devastated health services, the government of
      Afghanistan has provided access to basic services mainly by contracting with non
      government organisations (NGOs), and more recently the Strengthening Mechanism
      (SM) of contracting with Provincial Health Offices. Community-based information
      about the public's views and experience of health services is scarce. METHODS:
      Field teams visited households in a stratified random sample of 30 communities in
      two districts in Kabul province, with health services mainly provided either by
      an NGO or through the SM and administered a questionnaire about household views,
      use, and experience of health services, including payments for services and
      corruption. They later discussed the findings with separate community focus
      groups of men and women. We calculated weighted frequencies of views and
      experience of services and multivariate analysis examined the related factors.
      RESULTS: The survey covered 3283 households including 2845 recent health service
      users. Some 42% of households in the SM district and 57% in the NGO district
      rated available health services as good. Some 63% of households in the SM
      district (adjacent to Kabul) and 93% in the NGO district ordinarily used
      government health facilities. Service users rated private facilities more
      positively than government facilities. Government service users were more
      satisfied in urban facilities, if the household head was not educated, if they
      had enough food in the last week, and if they waited less than 30 minutes. Many
      households were unwilling to comment on corruption in health services; 15% in the
      SM district and 26% in the NGO district reported having been asked for an
      unofficial payment. Despite a policy of free services, one in seven users paid
      for treatment in government facilities, and three in four paid for medicine
      outside the facilities. Focus groups confirmed people knew payments were
      unofficial; they were afraid to talk about corruption. CONCLUSIONS: Households
      used government health services but preferred private services. The experience of
      service users was similar in the SM and NGO districts. People made unofficial
      payments in government facilities, whether SM or NGO run. Tackling corruption in
      health services is an important part of anti-corruption measures in Afghanistan.

PMID- 22376192
TI  - Effects of training on bone mass in older adults: a systematic review.
AB  - It is widely recognized that the risk of fractures is closely related to the
      typical decline in bone mass during the ageing process in both women and men.
      Exercise has been reported as one of the best non-pharmacological ways to improve
      bone mass throughout life. However, not all exercise regimens have the same
      positive effects on bone mass, and the studies that have evaluated the role of
      exercise programmes on bone-related variables in elderly people have obtained
      inconclusive results. This systematic review aims to summarize and update present
      knowledge about the effects of different types of training programmes on bone
      mass in older adults and elderly people as a starting point for developing future
      interventions that maintain a healthy bone mass and higher quality of life in
      people throughout their lifetime. A literature search using MEDLINE and the
      Cochrane Central Register of Controlled Trials databases was conducted and
      bibliographies for studies discussing the effect of exercise interventions in
      older adults published up to August 2011 were examined. Inclusion criteria were
      met by 59 controlled trials, 7 meta-analyses and 8 reviews. The studies included
      in this review indicate that bone-related variables can be increased, or at least
      the common decline in bone mass during ageing attenuated, through following
      specific training programmes. Walking provides a modest increase in the loads on
      the skeleton above gravity and, therefore, this type of exercise has proved to be
      less effective in osteoporosis prevention. Strength exercise seems to be a
      powerful stimulus to improve and maintain bone mass during the ageing process.
      Multi-component exercise programmes of strength, aerobic, high impact and/or
      weight-bearing training, as well as whole-body vibration (WBV) alone or in
      combination with exercise, may help to increase or at least prevent decline in
      bone mass with ageing, especially in postmenopausal women. This review provides,
      therefore, an overview of intervention studies involving training and bone
      measurements among older adults, especially postmenopausal women. Some novelties
      are that WBV training is a promising alternative to prevent bone fractures and
      osteoporosis. Because this type of exercise under prescription is potentially
      safe, it may be considered as a low impact alternative to current methods
      combating bone deterioration. In other respects, the ability of peripheral
      quantitative computed tomography (pQCT) to assess bone strength and geometric
      properties may prove advantageous in evaluating the effects of training on bone
      health. As a result of changes in bone mass becoming evident by pQCT even when
      dual energy X-ray absortiometry (DXA) measurements were unremarkable, pQCT may
      provide new knowledge about the effects of exercise on bone that could not be
      elucidated by DXA. Future research is recommended including longest-term exercise
      training programmes, the addition of pQCT measurements to DXA scanners and more
      trials among men, including older participants.

PMID- 22376193
TI  - Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in
      relationship to United States Food and Drug Administration (FDA) guidelines.
AB  - PURPOSE: Myocardial late gadolinium enhancement was originally validated using
      higher than label-recommended doses of gadolinium chelate. The objective of this
      study was to evaluate available evidence for various gadolinium dosing regimens
      used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic
      systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also
      examined. METHODS: We conducted a meta-analysis of peer reviewed publications
      from January, 2004 to December, 2010. Major subject search headings (MeSh) terms
      from the National Library of Medicine's PubMed were: contrast media, gadolinium,
      heart, magnetic resonance imaging; searches were limited to human studies with
      abstracts published in English. Case reports, review articles, editorials, MRA
      related papers and all reports that did not indicate gadolinium type or weight
      based dose were excluded. For all included references, full text was available to
      determine the total administered gadolinium dose on a per kg basis. Average and
      median dose values were weighted by the number of subjects in each study.
      RESULTS: 399 publications were identified in PubMed; 233 studies matched the
      inclusion criteria, encompassing 19,934 patients with mean age 54.2 +/- 11.4
      (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to
      myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted
      mean contrast dose were 0.15 and 0.16 +/- 0.06 mmol/kg, respectively. Median
      contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean
      contrast doses for the years 2005-2010 were: 0.19 +/- 0.03, 0.18 +/- 0.04, 0.18
      +/- 0.10, 0.18 +/- 0.03, 0.18 +/- 0.04 and 0.18 +/- 0.04 mmol/kg, respectively (p
      for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type
      [114 (48.9%) studies]. No change in mean gadolinium dose was present before,
      versus after the Food and Drug Administration (FDA) black box warning (p > 0.05).
      Three multi-center dose ranging trials have been published for cardiac MRI
      applications. CONCLUSION: CMR studies in the peer-reviewed published literature
      routinely use higher gadolinium doses than regulatory agencies indicated in the
      package leaflet. Clinical trials should be supported to determine the appropriate
      doses of gadolinium for CMR studies.

PMID- 22376194
TI  - Intensive aerobic cycling training with lower limb weights in Chinese patients
      with chronic stroke: discordance between improved cardiovascular fitness and
      walking ability.
AB  - PURPOSE: To evaluate the effect of aerobic cycling training with lower limb
      weights on cardiovascular fitness (peak VO(2)) and walking ability in chronic
      stroke survivors, and to investigate the relationship between changes in these
      parameters. METHODS: 133 Chinese patients with chronic hemiparetic stroke (mean
      age 58 years) were randomized to either 8-week (5*/week) aerobic cycling training
      with lower limb weights group (n = 68) or a low-intensity overground walking
      group (n = 65). Peak VO(2), 6-minute walk distance (6MWD), knee muscle strength,
      balance and spasticity were measured before and after intervention. RESULTS:
      Cycling training increased peak VO(2) (24% vs. 3%, p < 0.001), 6MWD (2.7% vs.
      0.5%, p < 0.001), paretic (11% vs. 1.6%, p < 0.001) and nonparetic knee strength
      (16% vs. 1.0%, p < 0.001). In the cycling group, percent changes in peak VO(2)
      were positively associated with those in paretic (r = 0.491, p < 0.001) and
      nonparetic knee strength (r = 0.432, p < 0.001). Increased 6MWD correlated
      significantly with improved balance, spasticity and paretic knee strength by the
      stepwise regression analysis (r(2) = 0.342, p = 0.004), but not fitness gains.
      CONCLUSIONS: The enhanced cardiovascular fitness after aerobic cycling training
      in Chinese patients with chronic stroke is not associated with the increased
      walking ability. Unparallel improvements in these parameters related different
      determinants may have implications for intervention strategy.

PMID- 22376195
TI  - "Anti-smoking data are exaggerated" versus "the data are clear and indisputable":
      examining letters to the editor about tobacco.
AB  - Media advocacy plays a unique role in tobacco control policy development. Letters
      to the editor in particular are an interesting form of media advocacy because
      they reflect community sentiment regarding the policy agenda and provide insight
      into the public debate. The authors used ethnographic context analysis to examine
      the techniques used by writers of 262 tobacco-related letters to the editor
      published in 61 newspapers across Missouri over a 2-year period when tobacco tax
      and smoke-free indoor air initiatives were occurring across the state. The
      authors found that pro-tobacco control letter writers often used didactic
      strategies, citing numbers and reports, to convey information and presented their
      training or experience as a health professional (e.g., M.D., Ph.D.) to add
      legitimacy to their arguments. Anti-tobacco control letter writers, in contrast,
      used narrative strategies to support their stance, claimed authority as a smoker
      or small business owner to legitimize their claims by relating to the audience,
      and used collectivity to capture the attention of policymakers. These results
      present the importance of strategic media advocacy in tobacco control. Tobacco
      control advocates should increase their use of narrative strategies and
      collectivity in order to better connect with the public and policymakers.

PMID- 22376196
TI  - Attitudes to cosmetic surgery among ethnic minority groups in Britain: cultural
      mistrust, adherence to traditional cultural values, and ethnic identity salience
      as protective factors.
AB  - Previous work has suggested that ethnic minority women have more negative
      attitudes to cosmetic surgery than British Whites, but reasons for this are not
      fully understood. To overcome this dearth in the literature, the present study
      asked 250 British Asian and 250 African Caribbean university students to complete
      measures of attitudes to cosmetic surgery, cultural mistrust, adherence to
      traditional cultural values, ethnic identity salience, self-esteem, and
      demographics. Preliminary analyses showed that there were significant between
      group differences only on cultural mistrust and self-esteem, although effect
      sizes were small (d values = .21-.37). Further analyses showed that more negative
      attitudes to cosmetic surgery were associated with greater cultural mistrust,
      stronger adherence to traditional values, and stronger ethnic identity salience,
      although these relationships were weaker for African Caribbean women than for
      British Asians. These results are discussed in relation to perceptions of
      cosmetic surgery among ethnic minority women. 

PMID- 22376197
TI  - Operationalising sexual and reproductive health and rights in sub-Saharan Africa:
      constraints, dilemmas and strategies.
AB  - BACKGROUND: The continued poor sexual and reproductive health (SRH) outcomes in
      sub-Saharan Africa highlight the difficulties in reforming policies and laws, and
      implementing effective programmes. This paper uses one international and two
      national case studies to reflect on the challenges, dilemmas and strategies used
      in operationalising sexual and reproductive health and rights (SRHR) in different
      African contexts. METHODS: The international case study focuses on the progress
      made by African countries in implementing the African Union's Maputo Plan of
      Action (for the Operationalisation of the Continental Policy Framework for Sexual
      and Reproductive Health and Rights) and the experiences of state and non-state
      stakeholders in this process. The case was developed from an evaluation report of
      the progress made by nine African countries in implementing the Plan of Action,
      qualitative interviews exploring stakeholders' experiences and perceptions of the
      operationalisation of the plan (carried out as part of the evaluation) in
      Botswana and Nigeria, and authors' reflections. The first national case study
      explores the processes involved in influencing Ghana's Domestic Violence Act
      passed in 2007; developed from a review of scientific papers and organisational
      publications on the processes involved in influencing the Act, qualitative
      interview data and authors' reflections. The second national case study examines
      the experiences with introducing the 2006 Sexual Offences Act in Kenya, and it is
      developed from organisational publications on the processes of enacting the Act
      and a review of media reports on the debates and passing of the Act. RESULTS:
      Based on the three cases, we argue that prohibitive laws and governments'
      reluctance to institute and implement comprehensive rights approaches to SRH,
      lack of political leadership and commitment to funding SRHR policies and
      programmes, and dominant negative cultural framing of women's issues present the
      major obstacles to operationalising SRH rights. Analysis of successes points to
      the strategies for tackling these challenges, which include forming and working
      through strategic coalitions, employing strategic framing of SRHR issues to
      counter opposition and gain support, collaborating with government, and employing
      strategic opportunism. CONCLUSION: The strategies identified show future pathways
      through which challenges to the realisation of SRHR in Africa can be tackled.

PMID- 22376199
TI  - Promising oxonitridosilicate phosphor host Sr3Si2O4N2: synthesis, structure, and
      luminescence properties activated by Eu2+ and Ce3+/Li+ for pc-LEDs.
AB  - A novel oxonitridosilicate phosphor host Sr(3)Si(2)O(4)N(2) was synthesized in
      N(2)/H(2) (6%) atmosphere by solid state reaction at high temperature using
      SrCO(3), SiO(2), and Si(3)N(4) as starting materials. The crystal structure was
      determined by a Rietveld analysis on powder X-ray and neutron diffraction data.
      Sr(3)Si(2)O(4)N(2) crystallizes in cubic symmetry with space group Pa 3, Z = 24,
      and cell parameter a = 15.6593(1) A. The structure of Sr(3)Si(2)O(4)N(2) is
      constructed by isolated and highly corrugated 12 rings which are composed of 12
      vertex-sharing [SiO(2)N(2)] tetrahedra with bridging N and terminal O to form
      three-dimensional tunnels to accommodate the Sr(2+) ions. The calculated band
      structure shows that Sr(3)Si(2)O(4)N(2) is an indirect semiconductor with a band
      gap ~ 2.84 eV, which is close to the experimental value ~ 2.71 eV from linear
      extrapolation of the diffuse reflection spectrum. Sr(3-x)Si(2)O(4)N(2):xEu(2+)
      shows a typical emission band peaking at ~600 nm under 460 nm excitation, which
      perfectly matches the emission of blue InGaN light-emitting diodes. For
      Ce(3+)/Li(+)-codoped Sr(3)Si(2)O(4)N(2), one excitation band is in the UV range
      (280-350 nm) and the other in the UV blue range (380-420 nm), which matches
      emission of near-UV light-emitting diodes. Emission of Sr(3
      2x)Si(2)O(4)N(2):xCe(3+),xLi(+) shows a asymmetric broad band peaking at ~520 nm.
      The long-wavelength excitation and emission of Eu(2+) and Ce(3+)/Li(+)-doped
      Sr(3)Si(2)O(4)N(2) make them attractive for applications in phosphor-converted
      white light-emitting diodes.

PMID- 22376198
TI  - Microbial community of predatory bugs of the genus Macrolophus (Hemiptera:
      Miridae).
AB  - BACKGROUND: The predatory mirids of the genus Macrolophus are key natural enemies
      of various economically important agricultural pests. Both M. caliginosus and M.
      pygmaeus are commercially available for the augmentative biological control of
      arthropod pests in European greenhouses. The latter species is known to be
      infected with Wolbachia -inducing cytoplasmic incompatibility in its host- but
      the presence of other endosymbionts has not been demonstrated. In the present
      study, the microbial diversity was examined in various populations of M.
      caliginosus and M. pygmaeus by 16S rRNA sequencing and denaturing gradient gel
      electrophoresis. RESULTS: Besides Wolbachia, a co-infection of 2 Rickettsia
      species was detected in all M. pygmaeus populations. Based on a concatenated
      alignment of the 16S rRNA gene, the gltA gene and the coxA gene, the first is
      phylogenetically related to Rickettsia bellii, whereas the other is closely
      related to Rickettsia limoniae. All M. caliginosus populations were infected with
      the same Wolbachia and limoniae-like Rickettsia strain as M. pygmaeus, but did
      not harbour the bellii-like Rickettsia strain. Interestingly, individuals with a
      single infection were not found. A PCR assay on the ovaries of M. pygmaeus and M.
      caliginosus indicated that all endosymbionts are vertically transmitted. The
      presence of Wolbachia and Rickettsia in oocytes was confirmed by a fluorescence
      in situ hybridisation. A bio-assay comparing an infected and an uninfected M.
      pygmaeus population suggested that the endosymbionts had minor effects on nymphal
      development of their insect host and did not influence its fecundity. CONCLUSION:
      Two species of the palaearctic mirid genus Macrolophus are infected with multiple
      endosymbionts, including Wolbachia and Rickettsia. Independent of the origin, all
      tested populations of both M. pygmaeus and M. caliginosus were infected with
      three and two endosymbionts, respectively. There was no indication that infection
      with endosymbiotic bacteria had a fitness cost in terms of development and
      fecundity of the predators.

PMID- 22376200
TI  - Numerical discretization-based estimation methods for ordinary differential
      equation models via penalized spline smoothing with applications in biomedical
      research.
AB  - Differential equations are extensively used for modeling dynamics of physical
      processes in many scientific fields such as engineering, physics, and biomedical
      sciences. Parameter estimation of differential equation models is a challenging
      problem because of high computational cost and high-dimensional parameter space.
      In this article, we propose a novel class of methods for estimating parameters in
      ordinary differential equation (ODE) models, which is motivated by HIV dynamics
      modeling. The new methods exploit the form of numerical discretization algorithms
      for an ODE solver to formulate estimating equations. First, a penalized-spline
      approach is employed to estimate the state variables and the estimated state
      variables are then plugged in a discretization formula of an ODE solver to obtain
      the ODE parameter estimates via a regression approach. We consider three
      different order of discretization methods, Euler's method, trapezoidal rule, and
      Runge-Kutta method. A higher-order numerical algorithm reduces numerical error in
      the approximation of the derivative, which produces a more accurate estimate, but
      its computational cost is higher. To balance the computational cost and
      estimation accuracy, we demonstrate, via simulation studies, that the trapezoidal
      discretization-based estimate is the best and is recommended for practical use.
      The asymptotic properties for the proposed numerical discretization-based
      estimators are established. Comparisons between the proposed methods and existing
      methods show a clear benefit of the proposed methods in regards to the trade-off
      between computational cost and estimation accuracy. We apply the proposed methods
      t an HIV study to further illustrate the usefulness of the proposed approaches.

PMID- 22376201
TI  - Sucrose induces rapid activation of CfSAPK, a mitogen-activated protein kinase,
      in Cephalostachyum fuchsianum Gamble cells.
AB  - Sucrose was recently demonstrated to function as a molecular signal. However,
      sucrose-specific sensing and signalling pathways remain largely undefined. Here,
      we show that Cephalostachyum fuchsianum sucrose-activated protein kinase (CfSAPK)
      is transiently and specifically activated by sucrose in C. fuchsianum Gamble
      suspension cells. The result suggested that CfSAPK participates in a sucrose
      signalling pathway. CfSAPK was partially purified from sucrose-treated cells and
      further analysed. Kinase activity assays revealed that CfSAPK preferentially used
      myelin basic protein (MBP) as substrate in vitro and strongly phosphorylate MBP
      threonine residue(s) and weakly phosphorylated MBP serine residue(s). Of the
      divalent cations tested, Mg(2+) was required for CfSAPK activation. Phosphatase
      treatment of CfSAPK abolished its kinase activity, indicating that
      phosphorylation is required for CfSAPK activation. Seven internal tryptic
      peptides identified from CfSAPK matched mitogen-activated protein kinases (MAPKs)
      in plants. CfSAPK cDNA was cloned using RT-PCR and rapid amplification of cDNA
      ends (RACE). CfSAPK cDNA encodes a 382-amino acid protein with a calculated
      molecular mass of 43,466.9 Da. The CfSAPK protein contains all 11 conserved
      kinase subdomains found in other Ser/Thr kinases. The amino acids sequence of
      CfSAPK is highly homologous to group A MAPKs in monocotyledon plants.

PMID- 22376203
TI  - Squaric acid mediated synthesis and biological activity of a library of linear
      and hyperbranched poly(glycerol)-protein conjugates.
AB  - Polymer-protein conjugates generated from side chain functional synthetic
      polymers are attractive because they can be easily further modified with, for
      example, labeling groups or targeting ligands. The residue specific modification
      of proteins with side chain functional synthetic polymers using the traditional
      coupling strategies may be compromised due to the nonorthogonality of the side
      chain and chain-end functional groups of the synthetic polymer, which may lead to
      side reactions. This study explores the feasibility of the squaric acid diethyl
      ester mediated coupling as an amine selective, hydroxyl tolerant, and hydrolysis
      insensitive route for the preparation of side-chain functional, hydroxyl
      containing, polymer-protein conjugates. The hydroxyl side chain functional
      polymers selected for this study are a library of amine end-functional, linear,
      midfunctional, hyperbranched, and linear-block-hyperbranched polyglycerol (PG)
      copolymers. These synthetic polymers have been used to prepare a diverse library
      of BSA and lysozyme polymer conjugates. In addition to exploring the scope and
      limitations of the squaric acid diethylester-mediated coupling strategy, the use
      of the library of polyglycerol copolymers also allows to systematically study the
      influence of molecular weight and architecture of the synthetic polymer on the
      biological activity of the protein. Comparison of the activity of PG-lysozyme
      conjugates generated from relatively low molecular weight PG copolymers did not
      reveal any obvious structure-activity relationships. Evaluation of the activity
      of conjugates composed of PG copolymers with molecular weights of 10000 or 20000
      g/mol, however, indicated significantly higher activities of conjugates prepared
      from midfunctional synthetic polymers as compared to linear polymers of similar
      molecular weight.

PMID- 22376204
TI  - Insight into the structural deformations of beta-cyclodextrin caused by alcohol
      cosolvents and guest molecules.
AB  - Beta-cyclodextrin (beta-CD) is an ideal candidate for a host molecule, and it is
      used as such in drug delivery and separation technology. The structural behavior
      of free beta-CD and host-guest complexes of beta-CD with two isoflavonoid isomers
      (puerarin and daidzin) in aqueous alcohol solutions, covering methanol, ethanol,
      2-propanol, and 1-propanol, was investigated through molecular dynamics (MD)
      simulations. The MD results highlighted aspects of the structural flexibility and
      rigidity of beta-CD in different alcohol solutions. The alcohol residence time
      within the beta-CD cavity, solvent distribution around beta-CD, and guest-induced
      structural changes were analyzed. Interaction with puerarin endowed beta-CD with
      a more rigid structure than with daidzin and a weaker ternary complex beta
      CD/puerarin/alcohol was formed with a local participation of water molecules. The
      retention behavior of puerarin and daidzin on a beta-CD-coupled medium was
      determined via chromatographic experiments and simulation results provided a
      structural explanation for such interactions.

PMID- 22376207
TI  - Scaling and root planing treatment for periodontitis to reduce preterm birth and
      low birth weight: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The aim of this study is to perform an updated systematic review and
      meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of
      scaling and root planing (SRP) in reducing the preterm-birth and low-birth-weight
      risks to analyze important subgroups and to further explore heterogeneity and
      bias risks in the pooled studies. METHODS: The entire Cochrane Library was
      searched (from 1990 to September 2011), MEDLINE (from 1950 to September 2011),
      CINAHL (from 1980 to September 2011), University of Michigan School of Dentistry
      "Dentistry and Oral Sciences" database (from 1990 to September 2011), conference
      proceedings, and the ClinicalTrials.gov database. Authors were contacted when
      clarification was needed. Selection criteria included the following: 1) RCTs that
      reported preterm-birth risk (<37 weeks) outcomes, 2) compared SRP treatment to
      either placebo or no treatment in pregnant patients with periodontitis, and 3)
      had a probing depth >4 mm or clinical attachment loss >2 mm for >= 1 site.
      Reviewers independently extracted data from each included study using a
      standardized, piloted form and assessed quality using a risk-of-bias tool modeled
      after Cochrane, and discrepancies were resolved. A random-effects model was used
      to calculate relative risks and 95% confidence intervals (CIs) for pooled data.
      For subgroup analysis with heterogeneity <50%, a fixed-effects model was used.
      RESULTS: After abstract review, 12 studies were identified by the search, and 11
      were included in the main meta-analysis (preterm birth <37 weeks). Overall
      quality and design of included studies was fair or good. For the main meta
      analysis, results ranged from risk ratio with periodontal treatment 0.14 (95% CI
      = 0.01, 2.55) to 1.24 (95% CI = 0.93, 1.67) for an overall risk ratio of 0.81
      (95% CI = 0.64, 1.02). When analyzed separately by subgroup for excess
      prematurity risk, the high-risk group (overall prematurity of 22.2% to 62.8%)
      showed combined risk ratios of 0.66 (95% CI = 0.54, 0.80). Remaining studies
      (overall prematurity of 4.0% to 10.4%) showed combined risk ratio of 0.97 (95% CI
      = 0.75, 1.24). CONCLUSIONS: This systematic review and meta-analysis indicates
      statistically significant effect in reducing risk of preterm birth for SRP in
      pregnant women with periodontitis for groups with high risks of preterm birth
      only. Future research should attempt to confirm these findings and further define
      groups in which risk reduction may be effective.

PMID- 22376208
TI  - Presence of JP2 and Non-JP2 Genotypes of Aggregatibacter actinomycetemcomitans
      and attachment loss in adolescents in Ghana.
AB  - BACKGROUND: Limited data are reported concerning the presence of A.
      actinomycetemcomitans and attachment loss (AL) in sub-Saharan countries. The
      authors investigate the carrier frequency of JP2 and non-JP2 genotypes of A.
      actinomycetemcomitans and the presence of AL in Ghanaian adolescents and evaluate
      socioeconomic conditions and oral hygiene practices. METHODS: Five hundred
      individuals (mean +/- SD age: 13.2 +/- 1.5 years) in public and private schools
      were interviewed about demographic characteristics and oral hygiene practices and
      were given a full-mouth periodontal examination. Subgingival plaque samples were
      obtained from periodontal sites around permanent first molars and incisors. The
      carrier status of A. actinomycetemcomitans at the individual level was determined
      based on results obtained by cultivation and polymerase chain reaction. RESULTS:
      The findings of this study show a relatively high carrier rate of JP2 and non-JP2
      genotypes of Aggregatibacter actinomycetemcomitans in the Ghanaian adolescent
      population and the presence of this bacterium is associated with the occurrence
      of AL. The overall carrier rate of A. actinomycetemcomitans was 54.4%, and the
      highly leukotoxic JP2 genotype was detected in 8.8% of the study population. A
      total of 107 (21.4%) individuals had >= 1 tooth with AL >= 3 mm. The majority of
      the individuals carrying A. actinomycetemcomitans (80.1%) (P <0.001) and of the
      periodontally diseased individuals (91.6%) (P <0.001) were found in public
      schools. CONCLUSIONS: A. actinomycetemcomitans and AL were frequently found in
      Ghanaian adolescents. The school type was the strongest predictor of both
      presence of A. actinomycetemcomitans and AL.

PMID- 22376209
TI  - The association of smoking and diabetes with periodontitis in a Korean
      population.
AB  - BACKGROUND: Smoking and diabetes are well-known risk factors for periodontitis.
      The aims of this study are to examine whether these factors are associated with
      periodontitis in representative samples of Koreans and to estimate the
      interaction impact of smoking and diabetes on periodontitis in this population.
      METHODS: The Korean National Oral Health Survey (KNOHS) 2006 collected nationally
      representative samples of oral epidemiologic data. A community periodontal index
      (CPI) of 3 to 4 and a CPI value of 0 to 2 were classified as periodontitis and
      non-periodontitis, respectively. A total of 4,118 participants from KNOHS 2006
      were interviewed on smoking and diabetes. Periodontitis was the outcome variable.
      Smoking and diabetes were the major explanatory variables. The confounders
      consisted of age, sex, education, occupation, monthly income, and residential
      area. Logistic regression analyses were used to evaluate the associations of
      smoking and diabetes with periodontitis after adjustment for confounders.
      RESULTS: The overall prevalence of periodontitis, current smoking, and self
      reported diabetes in Korean adults was 10.1%, 25.9%, and 4.5%, respectively.
      Associations of smoking and diabetes with periodontitis were : current smokers,
      odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.02 to 1.90; and
      diabetes, OR = 1.21, 95% CI = 0.82 to 1.77. The association between diabetes and
      periodontitis was not significant and there were no synergistic interactions of
      smoking and diabetes on periodontitis. CONCLUSIONS: The results suggest that
      smoking has a significant impact on the periodontal health of Korean adults, but
      the combined effect of smoking and diabetes had no significant impact.

PMID- 22376210
TI  - A placebo-controlled trial to evaluate an anesthetic gel when probing in patients
      with advanced periodontitis.
AB  - BACKGROUND: The baseline periodontal examination is reported to be a painful
      dental procedure, but currently there are limited practical techniques to reduce
      this pain. The objective of this study is to evaluate the efficacy of an
      intrapocket anesthetic gel in the reduction of pain on periodontal probing in a
      group of untreated patients with generalized chronic periodontitis (CP). METHODS:
      This study is a randomized, double-masked, split-mouth, placebo-controlled trial.
      Thirty consecutive patients meeting the inclusion criteria had full-mouth
      periodontal probing performed in a split-mouth (right side/left side) manner.
      Before probing, both quadrants on each side were isolated and had a randomized
      gel (either placebo or test gel) placed in the periodontal pockets for 30
      seconds. Pain was measured using two ungraded 100-mm horizontal visual analog
      scales (VAS) representing right and left sides of the mouth. RESULTS: The mean +/
      SD VAS for the test gel was 23.5 +/- 16.8 mm, and the mean +/- SD VAS for the
      placebo gel was 23.5 +/- 14.6 mm. The mean +/- SD difference in VAS was 51.6 +/-
      28.11 mm in favor of the anesthetic gel, and only age was found to be a
      marginally significant predictor. CONCLUSIONS: The VAS pain scores showed
      favorable anesthetic efficacy of the test gel compared to a placebo gel in
      reducing patients' pain on periodontal probing in a group of patients with
      generalized CP. It suggests that the gel may be used for patients who find the
      full-mouth periodontal probing experience particularly painful in view of other
      tested alternatives.

PMID- 22376211
TI  - Deep brain stimulation in China: present and future.
AB  - OBJECTIVE: We reviewed the clinical applications, academic communications, and
      specialized training required for deep brain stimulation (DBS) in China. Current
      problems and possible solutions also were discussed. MATERIALS AND METHODS: We
      reviewed all literature on DBS by Chinese authors. The WANFANG and PUBMED (2000
      2009) data bases were searched to collect publications on DBS by Chinese authors.
      To compare the Chinese academic publications on DBS with those by American
      authors, data from publications by American authors also were collected.
      Information on the DBS population as categorized by year, by province, and by
      indication was collected from the Medtronic Neuromodulation data base. RESULTS:
      From 2000 to 2009, there were 187 publications on DBS in Chinese journals and 23
      in English journals by Chinese authors. American peers contributed 569 articles
      during the same period. In total, 2082 patients received DBS treatment in China
      by the end of 2009. CONCLUSIONS: DBS has evolved significantly during the past
      decade in China. There are still several problems. The advent of Chinese homemade
      DBS hardware, multidisciplinary cooperation, and the establishment of guidelines
      and regulations for DBS will improve the application of this surgical treatment
      in China.

PMID- 22376212
TI  - Membrane perforation in sinus floor elevation - piezoelectric device versus
      conventional rotary instruments for osteotomy: an experimental study.
AB  - PURPOSE: Sinus membrane perforation is the most common intraoperative
      complication of maxillary sinus floor elevation (MSFE) procedures and frequently
      causes postoperative problems. Piezoelectric devices have been claimed to reduce
      the frequency of membrane perforations although no clear evidence supports this
      view. MATERIALS AND METHODS: Ten surgeons with different expertise levels
      performed 80 MSFEs in selected lamb heads, with rotary and piezoelectric
      instruments following standard protocols. After the procedures, specimens were
      coded and perforations or tears determined through a microscope. RESULTS: No
      significant differences in terms of thickness either of the sinus lateral wall
      (xi -xj  = 73.2; 95% confidence interval [CI] = 45.3-191.8) or the membrane (xi 
      xj  = 24.2; 95% CI = -29.4 to 77.9) were identified between the specimens
      allocated to each group. Nine membrane perforations (11.2%) occurred during the
      study, all within the lower expertise group. Membrane elevation by hand
      instruments caused five perforations (40%) in the rotary instrument group and one
      in the piezoelectric group. Expert surgeons produced no membrane perforations,
      the size of the antrostomy that was smaller in the piezoelectric group being the
      only significant difference between the rotary and piezoelectric groups.
      CONCLUSIONS: The use of piezoelectric material for MSFE reduces the frequency of
      membrane perforation among surgeons with a limited experience.

PMID- 22376214
TI  - Disability and kidney transplantation in the United States.
AB  - Transplantation is the treatment of choice for patients with end-stage renal
      disease. Despite complete or partial restoration of renal function, many
      recipients after transplant continue to self-identify as disabled. It is a
      designation required for federal healthcare assistance pre-transplant, but in
      some cases, post-transplantation, the designation is misapplied. When kidney
      recipients bear the label of disabled, regardless if the disability is real or
      perceived, they are less likely to participate in work and social activities.
      Although transplantation improves quality of life, for many recipients the
      designation of disability can extend an unintended, negative impact. It is well
      recognized that kidney recipients return to employment, education, and social
      activities after transplantation. However, there is a portion of the recipient
      population that can work but chooses not to engage. A large part of the
      phenomenon is related to disability status and the federal financing of kidney
      disease. This paper summarizes the history of the relationship between disability
      and kidney transplantation, the potential pitfalls associated with the
      relationship, and evidence-based strategies designed to mitigate or lead to
      mitigation of the unfavorable effects associated with misappropriated, perceived
      disability after kidney transplantation.

PMID- 22376216
TI  - Killer cell immunoglobulin-like receptor gene polymorphisms predispose
      susceptibility to Epstein-Barr virus associated hemophagocytic
      lymphohistiocytosis in Chinese children.
AB  - Epstein-Barr virus associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a
      high mortality rate among children. The pathogenesis of, and underlying
      predisposing factors for, EBV-HLH are as yet unclear; however, natural killer
      cells may play a key role in progression of the disease. This study attempted to
      determine whether killer cell immunoglobulin-like receptor (KIR) gene
      polymorphisms are responsible for susceptibility to EBV-HLH. Of the 125 children
      with EBV infection studied, 59 had EBV-HLH and 66 patients had EBV associated
      infectious mononucleosis (IM) without HLH. The control group was 146 normal
      children without immune deficiency. KIR polymorphisms were determined by
      polymerase chain reaction with sequence-specific primers. KIR polymorphism data
      were analyzed using the X(2) test or Fisher's exact test. The overall observed
      carrier frequency (OF) of KIR2DS5 was significantly higher in EBV-HLH patients
      than in IM patients and normal controls (49.2% versus 31.8%, P = 0.048; 49.2%
      versus 31.5%, P = 0.018, respectively), and the odds ratios (95% confidence
      interval) were 2.071 (1.001-4.286) and 2.101(1.132-3.900) respectively. The OF of
      KIR3DS1 was significantly higher in the EBV-HLH patients than in the IM patients
      (47.4% versus 24.6%, P = 0.012), but not different from normal controls. In
      summary, KIR polymorphisms may be involved in the development of EBV-HLH, with
      KIR2DS5 promoting susceptibility to this disease. The obtained KIR data will
      enrich the understanding of genetic relationships among diseases associated with
      EBV infection in children.

PMID- 22376218
TI  - Heterogeneity of the HIV epidemic in the general population of Karnataka state,
      south India.
AB  - BACKGROUND: In the context of AVAHAN, the India AIDS Initiative of the Bill &
      Melinda Gates Foundation, general population surveys (GPS) were carried out
      between 2006 and 2008 in Belgaum (northern), Bellary (mid-state) and Mysore
      (southern) districts of Karnataka state, south India. Data from these three
      surveys were analysed to understand heterogeneity in HIV risk. METHODS: Outcome
      variables were the prevalence of HIV and sexually transmitted infections (STIs).
      Independent variables included age, district, place of residence, along with
      socio-demographic, medical and behavioural characteristics. Multivariate logistic
      regression was undertaken to identify characteristics associated with HIV and
      differences between districts, incorporating survey statistics to consider
      weights and cluster effects. RESULTS: The participation rate was 79.0% for the
      interview and 72.5% for providing a blood or urine sample that was tested for
      HIV. Belgaum had the highest overall HIV (1.43%) and Herpes simplex type-2 (HSV
      2) (16.93%) prevalence, and the lowest prevalence of curable STIs. In Belgaum,
      the HIV epidemic is predominantly rural, and among women. In Bellary, the
      epidemic is predominantly in urban areas and among men, and HIV prevalence was
      1.18%. Mysore had the lowest prevalence of HIV (0.80%) and HSV-2 (10.89%) and the
      highest prevalence of curable STIs. Higher HIV prevalence among men was
      associated with increasing age (p<0.001), and with history of STIs
      (AOR=2.44,95%CI:1.15-5.17). Male circumcision was associated with lower HIV
      prevalence (AOR=0.33,95%CI:0.13-0.81). Higher HIV prevalence among women was
      associated with age (AOR25-29years=11.22,95%CI:1.42-88.74, AOR30
      34years=13.13,95%CI:1.67-103.19 and AOR35-39years=11.33,95%CI:1.32-96.83), having
      more than one lifetime sexual partner (AOR=4.61,95%CI:1.26-16.91) and having ever
      used a condom (AOR=3.32,95%CI:1.38-7.99). Having a dissolved marriage (being
      widowed/divorced/separated) was the strongest predictor (AOR=10.98,95%CI: 5.35
      22.57) of HIV among women. Being a muslim woman was associated with lower HIV
      prevalence (AOR=0.27,95%CI:0.08-0.87). CONCLUSION: The HIV epidemic in Karnataka
      shows considerable heterogeneity, and there appears to be an increasing gradient
      in HIV prevalence from south to north. The sex work structure in the northern
      districts may explain the higher prevalence of HIV in northern Karnataka. The
      higher prevalence of HIV and HSV-2 and lower prevalence of curable STIs in
      Belgaum suggests a later epidemic phase. Similarly, higher prevalence of curable
      STIs and lower HIV and HSV-2 prevalence in Mysore suggests an early phase
      epidemic.

PMID- 22376219
TI  - Tetravalent titanium, zirconium, and cerium oxo and peroxo complexes containing
      an imidodiphosphinate ligand.
AB  - Dinuclear Ti(IV), Zr(IV), and Ce(IV) oxo and peroxo complexes containing the
      imidodiphosphinate ligand [N(i-Pr(2)PO)(2)](-) have been synthesized and
      structurally characterized. Treatment of Ti(O-i-Pr)(2)Cl(2) with KN(i-Pr(2)PO)(2)
      afforded the Ti(IV) di-MU-oxo complex [Ti{N(i-Pr(2)PO)(2)}(2)](2)(MU-O)(2) (1)
      that reacted with 35% H(2)O(2) to give the peroxo complex Ti[N(i
      Pr(2)PO)(2)](2)(eta(2)-O(2)) (2). Treatment of HN(i-Pr(2)PO)(2) with Zr(O-t
      Bu)(4) and Ce(2)(O-i-Pr)(8)(i-PrOH)(2) afforded the di-MU-peroxo-bridged dimers
      [M{N(i-Pr(2)PO)(2)}(2)](2)(MU-O(2))(2) [M = Zr (3), Ce (4)]. 4 was also obtained
      from the reaction of Ce[N(i-Pr(2)PO)(2)](3) with 35% H(2)O(2). Treatment of
      (Et(4)N)(2)[CeCl(6)] with 3 equiv of KN(i-Pr(2)PO)(2) afforded Ce[N(i
      Pr(2)PO)(2)](3)Cl (5). Reaction of (Et(4)N)(2)[CeCl(6)] with 2 equiv of KN(i
      Pr(2)PO)(2) in acetonitrile, followed by treatment with Ag(2)O, afforded the MU
      oxo-bridged complex [Ce{N(i-Pr(2)PO)(2)}Cl](2)[MU-N(i-Pr(2)PO)(2)](2)(MU-O) (6).
      6 undergoes ligand redistribution in CH(2)Cl(2) in air to give 5. The solid-state
      structures of [K(2){N(i-Pr(2)PO)(2)}(2)(H(2)O)(8)](n) and complexes 1-6 have been
      determined.

PMID- 22376220
TI  - In vitro biological activities of the essential oil from the 'resurrection plant'
      Myrothamnus moschatus (Baillon) Niedenzu endemic to Madagascar.
AB  - The essential oil of the 'resurrection plant' Myrothamnus moschatus (Baillon)
      Niedenzu endemic to Madagascar, where it is used in traditional medicine, was
      investigated for the first time for some biological activities. GC-FID and GC-MS
      analyses revealed trans-pinocarveol (35.6%), pinocarvone (20.0%), beta-selinene
      (8.5%) and perillyl acetate (6.0%) as the major essential oil constituents. The
      oil strongly inhibited MDA-MB 231 (human breast adenocarcinoma) cells, with an
      IC(50) of 15 ug mL(-1), and the growth of Candida albicans, with an inhibition
      diameter of 18 mm, while its antioxidant activity, measured by DPPH and ABTS
      assay, proved to be negligible.

PMID- 22376221
TI  - Retrospective analysis of an efficient peripheral blood stem cell collection and
      the relation between infused cell dose and clinical outcome in patients with
      malignant lymphoma and multiple myeloma.
AB  - INTRODUCTION: Etoposide (VP16) is a drug used not only for the treatment of
      lymphoma but also for the collection of peripheral blood stem cells (PBSCs). We
      analysed the efficacy and adverse effects of collecting PBSCs and the relation
      between the infused cell dose and the clinical outcome in lymphoid malignancies.
      METHOD: Investigating 30 patients with non-Hodgkin's lymphoma, one patient with
      Hodgkin's lymphoma, and five patients with multiple myeloma, we compared the
      effects of several doses of etoposide with those of CHOP or CHOP-like treatments
      or salvage treatments. We also analysed the relation between the amount of
      CD34(+) cells collected (above or below 5.0 * 10(6) /kg/day) and prognosis of
      these patients. RESULTS: We found the collected cell count to be highest in
      patients treated with 500 mg/m(2) of VP16 and lowest in those not treated with
      VP16 (P = 0.0073). A CD34(+) cell count above 100/MUL on the collection day
      indicates that the target amount of CD34(+) cells (4.0 * 10(6) /kg) can be
      readily obtained and was reached most rapidly by the patients who had received
      500 mg/m(2) of VP16 (P = 0.01). The longer duration of neutropenia in those
      patients (P = 0.000006) resulted in longer antibiotic treatment (P = 0.0052).
      Both progression-free survival (PFS) and overall survival (OS) were better for
      the patients who yielded more than 5.0 * 10(6) CD34(+) cells/kg/day (P = 0.087
      for PFS and P < 0.033 for OS). CONCLUSION: We show here that 3 days of VP16 at
      500 mg/m(2) was useful for the collection of PBSCs and that patients who yielded
      more than 5.0 * 10(6) CD34(+) cells/kg/day survived longer than those who yielded
      less.

PMID- 22376222
TI  - Comparing decision making between cancer patients and the general population:
      thoughts, emotions, or social influence?
AB  - This study extends a risk information seeking and processing model to explore the
      relative effect of cognitive processing strategies, positive and negative
      emotions, and normative beliefs on individuals' decision making about potential
      health risks. Most previous research based on this theoretical framework has
      examined environmental risks. Applying this risk communication model to study
      health decision making presents an opportunity to explore theoretical boundaries
      of the model, while also bringing this research to bear on a pressing medical
      issue: low enrollment in clinical trials. Comparative analysis of data gathered
      from 2 telephone surveys of a representative national sample (n = 500) and a
      random sample of cancer patients (n = 411) indicated that emotions played a more
      substantive role in cancer patients' decisions to enroll in a potential trial,
      whereas cognitive processing strategies and normative beliefs had greater
      influences on the decisions of respondents from the national sample.

PMID- 22376223
TI  - Spatial memory decline after masticatory deprivation and aging is associated with
      altered laminar distribution of CA1 astrocytes.
AB  - BACKGROUND: Chewing imbalances are associated with neurodegeneration and are risk
      factors for senile dementia in humans and memory deficits in experimental
      animals. We investigated the impact of long-term reduced mastication on spatial
      memory in young, mature and aged female albino Swiss mice by stereological
      analysis of the laminar distribution of CA1 astrocytes. A soft diet (SD) was used
      to reduce mastication in the experimental group, whereas the control group was
      fed a hard diet (HD). Assays were performed in 3-, 6- and 18-month-old SD and HD
      mice. RESULTS: Eating a SD variably affected the number of astrocytes in the CA1
      hippocampal field, and SD mice performed worse on water maze memory tests than HD
      mice. Three-month-old mice in both groups could remember/find a hidden platform
      in the water maze. However, 6-month-old SD mice, but not HD mice, exhibited
      significant spatial memory dysfunction. Both SD and HD 18-month-old mice showed
      spatial memory decline. Older SD mice had astrocyte hyperplasia in the strata
      pyramidale and oriens compared to 6-month-old mice. Aging induced astrocyte
      hypoplasia at 18 months in the lacunosum-moleculare layer of HD mice.
      CONCLUSIONS: Taken together, these results suggest that the impaired spatial
      learning and memory induced by masticatory deprivation and aging may be
      associated with altered astrocyte laminar distribution and number in the CA1
      hippocampal field. The underlying molecular mechanisms are unknown and merit
      further investigation.

PMID- 22376226
TI  - Temporal profile of functional visual rehabilitative outcomes modulated by
      transcranial direct current stimulation.
AB  - OBJECTIVES: We have previously reported that transcranial direct current
      stimulation (tDCS) delivered to the occipital cortex enhances visual functional
      recovery when combined with three months of computer-based rehabilitative
      training in patients with hemianopia. The principal objective of this study was
      to evaluate the temporal sequence of effects of tDCS on visual recovery as they
      appear over the course of training and across different indicators of visual
      function. METHODS: Primary objective outcome measures were 1) shifts in visual
      field border and 2) stimulus detection accuracy within the affected hemifield.
      These were compared between patients randomized to either vision restoration
      therapy (VRT) combined with active tDCS or VRT paired with sham tDCS. Training
      comprised two half-hour sessions, three times a week for three months. Primary
      outcome measures were collected at baseline (pretest), monthly interim intervals,
      and at posttest (three months). As secondary outcome measures, contrast
      sensitivity and reading performance were collected at pretest and posttest time
      points only. RESULTS: Active tDCS combined with VRT accelerated the recovery of
      stimulus detection as between-group differences appeared within the first month
      of training. In contrast, a shift in the visual field border was only evident at
      posttest (after three months of training). tDCS did not affect contrast
      sensitivity or reading performance. CONCLUSIONS: These results suggest that tDCS
      may differentially affect the magnitude and sequence of visual recovery in a
      manner that is task specific to the type of visual rehabilitative training
      strategy employed.

PMID- 22376227
TI  - Summary of AHRQ's Comparative Effectiveness Review of Disease-Modifying
      Antirheumatic Drugs for Children with Juvenile Idiopathic Arthritis.
AB  - BACKGROUND: A systematic review on the comparative effectiveness of disease
      modifying antirheumatic drugs (DMARDs) used to treat children with juvenile
      idiopathic arthritis (JIA) was published by the Agency for Health Care Research
      and Quality (AHRQ) in September 2011. Studies from 198 articles included in the
      review addressed the benefits and harms of DMARDs compared with conventional
      treatments and other DMARDs used to treat JIA. The review also incorporated
      studies comparing various clinical tools used for diagnosing JIA and measuring
      disease activity. Clinical outcome measures were analyzed to determine the most
      effective methods to measure disease state. The lack of current research for the
      treatment of JIA motivated AHRQ to contract with researchers to synthesize the
      available information with the intent of enabling health professionals to make
      evidence-based practice decisions for their patients. The review alsohighlights
      gaps in the research and areas that need to be addressed in the future.
      OBJECTIVES: To (a) educate health care practitioners on the findings from AHRQ's
      2011 comparative effectiveness review on DMARDs used to treat children with JIA,
      (b) apply review findings to make diagnosis and treatment decisions in clinical
      practice, and (c) recognize limitations and gaps n the current research relating
      to the comparative benefits and harms of DMARDs for treatment of JIA. SUMMARY:
      JIA is a chronic inflammatory disease affecting approximately 300,000 children
      and adolescents in the United States.1 Initially manifesting with inflammation,
      swelling, pain, and stiffness of the joints, the disease as no apparent or known
      cause. JIA is a clinical diagnosis based on several actors including the number
      of affected joints and the involvement of other tissues (e.g., the skin and
      lymphoid tissues), and JIA has 7 categories: systemic-onset arthritis,
      oligoarthritis, rheumatoid-factor positive polyarthritis, rheumatoid-factor
      negative polyarthritis, enthesitis-related arthritis, psoriatic arthritis, and
      undifferentiated arthritis.2 Complete remission and resolution of disease
      activity are the ultimate treatment goals; however, there is no present cure.
      Inhibition of inflammation, prevention of joint damage, and promotion of a high
      level of functioning are the immediate goals of treatment. Even with treatment,
      patients with JIA continue to experience disease activity, joint destruction,
      suboptimal function, and impaired quality of life, all of which extend into
      adulthood.3 JIA can be severely debilitating and places a heavy physical and
      psychological burden on children and families affected by the disease.
      Methotrexate is a nonbiologic DMARD with an unknown mechanism of action.
      Methotrexate has been used for so long in the treatment of JIA that it is
      frequently considered a part of conventional treatment; the evidence shows that
      methotrexate is superior to conventional treatment with NSAIDsand/or intra
      articular corticosteroids. The introduction of newer biologic DMARDs has spawned
      optimism that treatment will increasingly lead to improved outcomes for JIA, but
      the evidence is insufficient to support superiority over methotrexate. There is
      moderate evidence to support the claim that continued treatment from 4 months to
      2 years with a biologic DMARD in children who have responded to a biologic DMARD
      decreases the risk of a flare. However, the safety of biologic DMARDs for long
      term use has not been determined and may be associated with the developmentof
      cancer. The association between tumor necrosis factor (TNF) alpha inhibitors and
      potential increased risk of lymphoma caused the U.S. Food and Drug Administration
      (FDA) to place boxed warning labels on biologic DMARDs including etancercept,
      infliximab, and adalimumab. The effectiveness of the DMARDs appears to vary among
      categories of JIA and the treatment history of individual patients. Except for
      methotrexate, there is insufficient evidence to support selection of a specific
      drug or drug class over another in the treatment of JIA. The AHRQ review examines
      the scientific literature on DMARDs used in children with JIA in an effort to
      synthesize what is known about the subject, and the comprehensive review
      identifies important research gaps in the literature that need to be addressed.
      Only 8 studies (in 9 publications) were rated "good quality" by the AHRQ
      investigators.

PMID- 22376228
TI  - Crowding-induced phase separation of Lennard-Jones particles: implications to
      nuclear structures in a biological cell.
AB  - We investigate the phase separation of Lennard-Jones (LJ) particles in the
      presence of cosolute crowders using molecular dynamics simulations. In the
      absence of crowders, LJ particles phase-separate and form liquid and vapor phases
      only when the attraction between LJ particles is strong enough such that
      k(B)T/epsilon is less than 1.085, where epsilon is the attraction strength of the
      LJ potential, k(B) is the Boltzmann constant, and T is the temperature. On the
      other hand, the phase separation of LJ particles is observed even for larger
      k(B)T/epsilon and thus for weaker attractions when volume exclusive, repulsive
      crowders are present. Although the impact of crowding becomes less significant as
      the attraction between crowders and LJ particles is increased, the phase
      separation observed from simulations containing both nonattractive and attractive
      crowders shows that the crowding-induced phase separation by nonattractive
      crowders is still very significant even in the presence of other attractive
      crowders. This occurs because not only LJ particles but also attractive crowders
      are subject to the excluded volume effect of nonattractive crowders and found
      together in the condensed phase. This study suggests that the excluded volume
      effect in the crowded nuclear environment may play a crucial role in the
      formation and maintenance of biological structures in a cell, such as nuclear
      bodies including nucleoli and cajal bodies.

PMID- 22376229
TI  - Critical care resources in the Solomon Islands: a cross-sectional survey.
AB  - BACKGROUND: There are minimal data available on critical care case-mix, care
      processes and outcomes in lower and middle income countries (LMICs). The
      objectives of this paper were to gather data in the Solomon Islands in order to
      gain a better understanding of common presentations of critical illness,
      available hospital resources, and what resources would be helpful in improving
      the care of these patients in the future. METHODS: This study used a mixed
      methods approach, including a cross sectional survey of respondents' opinions
      regarding critical care needs, ethnographic information and qualitative data.
      RESULTS: The four most common conditions leading to critical illness in the
      Solomon Islands are malaria, diseases of the respiratory system including
      pneumonia and influenza, diabetes mellitus and tuberculosis. Complications of
      surgery and trauma less frequently result in critical illness. Respondents
      emphasised the need for basic critical care resources in LMICs, including
      equipment such as oximeters and oxygen concentrators; greater access to
      medications and blood products; laboratory services; staff education; and the
      need for at least one national critical care facility. CONCLUSIONS: A large
      degree of critical illness in LMICs is likely due to inadequate resources for
      primary prevention and healthcare; however, for patients who fall through the net
      of prevention, there may be simple therapies and context-appropriate resources to
      mitigate the high burden of morbidity and mortality. Emphasis should be on the
      development and acquisition of simple and inexpensive tools rather than
      complicated equipment, to prevent critical care from unduly diverting resources
      away from other important parts of the health system.

PMID- 22376230
TI  - Culture, social class, and independence-interdependence: the case of Chinese
      adolescents.
AB  - Social class demarcates sociocultural environments differing in the relative
      abundance and scarcity of resources, which in turn differentially afford
      independent and interdependent psychological processes. The relationships between
      social class and psychological processes are well documented in Western
      populations but less so elsewhere. Examining such a relationship is particularly
      important in China, with its unique historical and sociocultural issues
      surrounding social class. This research examined the relationship between social
      class and independence-interdependence among Chinese adolescents (N = 1184).
      Findings were consistent across a diverse array of psychological processes
      implicated by independence-interdependence: Participants with well-educated
      parents experienced more socially disengaging emotions and a higher level of self
      esteem, and were more inclined toward dispositional attribution and focused
      attention, compared to participants with less well-educated parents. These
      findings highlight the cross-cultural commonality in the relationship between
      social class and independence-interdependence. 

PMID- 22376232
TI  - Soft tissue preservation and pink aesthetics around single immediate implant
      restorations: a 1-year prospective study.
AB  - PURPOSE: (1) To document soft tissue aspects using a specific protocol for
      immediate implant treatment (IIT) following single-tooth removal; (2) to evaluate
      whether this protocol allows preservation of pink aesthetics as objectively
      assessed. MATERIALS AND METHODS: Patients with a thick gingival biotype and
      intact buccal bone wall upon extraction of a single tooth in the aesthetic zone
      (15-25) were consecutively treated. The protocol included flapless extraction and
      implant surgery, socket grafting, immediate nonocclusal loading with a screw
      retained provisional crown, and replacement by a permanent crown 6 months
      thereafter. The outcome was assessed after 3, 6, and 12 months. Cases
      demonstrating major alveolar process remodeling and/or advanced midfacial
      recession (>1 mm) at 3 months were additionally treated with a connective tissue
      graft (CTG). The emergence profile of the provisional crown was replicated for
      all permanent crowns. RESULTS: Twenty-two patients (12 men, 10 women; mean age
      50) were treated after tooth extraction for nonperiodontal reasons using a novel
      bone condensing implant with variable-thread design, conical connection, and
      platform switch (NobelActive(r), Nobel Biocare, Goteborg, Sweden). One implant
      failed and mean marginal bone loss was 0.1 mm (p = .059). Temporary mesial
      papilla reduction occurred, whereas distal papilla reduction was permanent (mean
      0.5 mm; p = .001). At 3 months, five cases demonstrated major alveolar process
      remodeling and two advanced midfacial recession. Hence, slight initial decline in
      the pink esthetic score (PES) (p = .053) was observed. CTG resulted in a steady
      improvement of the PES after 3 months (p <= .037). At 12 months, pink aesthetics
      (mean PES 12.15) was comparable to the preoperative status (mean PES 11.86; p =
      .293). Distal papillae had significantly deteriorated (p = .020) in this time
      span, whereas midfacial contour had significantly improved (p = .005).
      CONCLUSIONS: Preservation of pink aesthetics is possible following IIT. However,
      to achieve that, CTG may be necessary in about one-third of the patients. Major
      alveolar process remodeling is the main reason for additional treatment.

PMID- 22376231
TI  - The presence of p47phox in liver parenchymal cells is a key mediator in the
      pathogenesis of alcoholic liver steatosis.
AB  - BACKGROUND: Reactive oxygen species contribute to steatosis and inflammation in
      alcoholic liver disease (ALD). Here, we evaluated the selective contribution of
      p47phox, a critical subunit of nicotinamide adenine dinucleotide phosphate
      oxidase (NADPH) oxidase complex, in liver parenchymal cells and in bone marrow
      (BM)-derived cells. METHODS: Female C57Bl/6 wild type [WT], total body p47phox
      deficient knockout [KO] or p47phox chimera mice generated by BM transplantation
      of p47phox-KO-BM into irradiated WT mice (WT/p47phox-KO-BM mice) received 5%
      Lieber-DeCarli alcohol or control (pair feeding) diet for 4 weeks. RESULTS:
      Alcohol-induced liver steatosis as measured by Oil Red O staining and serum
      triglyceride up-regulation were prevented in p47phox-KO mice but not in
      WT/p47phox-KO-BM chimeras compared to WT controls. Serum alanine aminotransferase
      (ALT) was significantly increased in alcohol-fed WT mice but not in p47phox-KO
      mice compared to pair-fed controls. There was no protection from alcohol-induced
      increase in ALT and liver damage in the WT/p47phox-KO-BM mice. Alcohol-induced
      liver steatosis was accompanied by up-regulation of the lipid droplet-stabilizing
      protein, adipocyte differentiation-related protein (ADRP), and the fatty acid
      synthesis-associated genes, fatty acid synthase (FASN) and acetyl-CoA carboxylase
      (ACACA). Total body deficiency in p47phox but not selective absence of p47phox in
      BM-derived cells prevented alcohol-induced up-regulation of ADRP, FASN, and ACACA
      in the liver. Finally, alcohol-induced activation and DNA binding of nuclear
      factor kappaB (NF-kappaB), a master regulator of inflammation, were significantly
      increased after alcohol feeding in WT but not in p47phox-KO mice. Selective
      deficiency of p47phox in BM-derived cells (WT/p47phox-KO-BM chimera) failed to
      prevent NF-kappaB induction after alcohol feeding. CONCLUSIONS: Total body
      deficiency in p47phox subunit of NADPH oxidase complex protects mice from alcohol
      induced liver steatosis via mechanisms involving ADRP, FASN, and ACACA as well as
      from alcohol-induced NF-kappaB activation. In contrast, selective absence of
      p47phox in BM-derived cells fails to provide protection via these mechanisms.
      These results suggest that p47phox in parenchymal cells plays a critical role in
      the pathogenesis of ALD.

PMID- 22376233
TI  - Use of social audits to examine unofficial payments in government health
      services: experience in South Asia, Africa, and Europe.
AB  - BACKGROUND: Unofficial payments in health services around the world are
      widespread and as varied as the health systems in which they occur. We reviewed
      the main lessons from social audits of petty corruption in health services in
      South Asia (Bangladesh, Pakistan), Africa (Uganda and South Africa) and Europe
      (Baltic States). METHODS: The social audits varied in purpose and scope. All
      covered representative sample communities and involved household interviews,
      focus group discussions, institutional reviews of health facilities, interviews
      with service providers and discussions with health authorities. Most audits
      questioned households about views on health services, perceived corruption in the
      services, and use of government and other health services. Questions to service
      users asked about making official and unofficial payments, amounts paid, service
      delivery indicators, and satisfaction with the service. RESULTS: Contextual
      differences between the countries affected the forms of petty corruption and
      factors related to it. Most households in all countries held negative views about
      government health services and many perceived these services as corrupt. There
      was little evidence that better off service users were more likely to make an
      unofficial payment, or that making such a payment was associated with better or
      quicker service; those who paid unofficially to health care workers were not more
      satisfied with the service. In South Asia, where we conducted repeated social
      audits, only a minority of households chose to use government health services and
      their use declined over time in favour of other providers. Focus groups indicated
      that reasons for avoiding government health services included the need to pay for
      supposedly free services and the non-availability of medicines in facilities,
      often perceived as due to diversion of the supplied medicines. CONCLUSIONS:
      Unofficial expenses for medical care represent a disproportionate cost for
      vulnerable families; the very people who need to make use of supposedly free
      government services, and are a barrier to the use of these services. Patient
      dissatisfaction due to petty corruption may contribute to abandonment of
      government health services. The social audits informed plans for tackling
      corruption in health services.

PMID- 22376235
TI  - Production and properties of lipase of Aeromonas sobria.
AB  - Aeromonas have been isolated from a wide variety of aquatic environments. However
      the number of Aeromonas in sea water is extremely small compared to that in fresh
      water. In in vitro culture, Aeromonas can grow in mediums containing NaCl at a
      concentration of 3.0%, this concentration corresponding to that of sea water. It
      is unclear why the number of Aeromonas is low in sea water. Exoproteins of
      bacteria are thought to be important for bacterial growth and survival in the
      environment. Previously, the present authors have shown that mediums containing
      3.0% NaCl suppress production of two proteases, serine protease and
      metalloprotease. In this experiment, other exoproteins whose production is
      influenced by the amount of NaCl in the medium were analyzed. A protein whose
      production is repressed in medium containing 3.0% NaCl was found and purified.
      Biological assay of the purified protein showed that it degrades tributyrin and
      hydrolyzes para-nitrophenyl-fatty acylesters. These results show that the protein
      is a lipase. Subsequently, the nucleotide sequence of the gene encoding the
      lipase was determined and the amount of mRNA of the lipase gene in the cells
      measured. It was found that transcription of the gene is not inhibited by NaCl in
      the medium. This result indicates that the lipase might be synthesized, but the
      folding process to become an active structure does not progress smoothly in a
      medium containing 3.0% NaCl.

PMID- 22376236
TI  - Air-stable spin-coated naphthalocyanine transistors for enhanced chemical vapor
      detection.
AB  - Air-stable organic thin-film transistor (OTFT) sensors fabricated using spin-cast
      films of 5,9,14,18,23,27,32,36-octabutoxy-2,3-naphthalocyanine (OBNc)
      demonstrated improved chemical vapor sensitivity and selectivity relative to
      vacuum-deposited phthalocyanine (H(2)Pc) OTFTs. UV-vis spectroscopy data show
      that annealed spin-cast OBNc films exhibit a red-shift in the OBNc Q-band
      lambda(max) which is generally diagnostic of improved pi-orbital overlap in
      phthalocyanine ring systems. Annealed OBNc OTFTs have mobilities of 0.06 cm(2) V(
      1) s(-1), low threshold voltages (|V(th)| < 1 V), and on/off ratios greater than
      10(6). These air-stable device parameters are utilized for sensing modalities
      which enhance the sensitivity and selectivity of OBNc OTFTs relative to H(2)Pc
      OTFTs. While both sensors exhibit mobility decreases for all analytes, only OBNc
      OTFTs exhibit V(th) changes for highly polar/nonpolar analytes. The observed
      mobility decreases for both sensors are consistent with electron donation trends
      via hydrogen bonding by basic analytes. In contrast, V(th) changes for OBNc
      sensors appear to correlate with the analyte's octanol-water partition
      coefficient, consistent with polar molecules stabilizing charge in the organic
      semiconductor film. The analyte induced V(th) changes for OBNc OTFTs can be
      employed to develop selective multiparameter sensors which can sense analyte
      stabilized fixed charge in the film.

PMID- 22376237
TI  - Determinants of condom breakage among female sex workers in Karnataka, India.
AB  - BACKGROUND: Condoms are effective in preventing the transmission of HIV and other
      sexually transmitted infections, when properly used. However, recent data from
      surveys of female sex workers (FSWs) in Karnataka in south India, suggest that
      condom breakage rates may be quite high. It is important therefore to quantify
      condom breakage rates, and examine what factors might precipitate condom
      breakage, so that programmers can identify those at risk, and develop appropriate
      interventions. METHODS: We explored determinants of reported condom breakage in
      the previous month among 1,928 female sex workers in four districts of Karnataka
      using data from cross-sectional surveys undertaken from July 2008 to February
      2009. Using stepwise multivariate logistic regression, we examined the possible
      determinants of condom breakage, controlling for several independent variables
      including the district and client load. RESULTS: Overall, 11.4% of FSWs reported
      at least one condom break in the previous month. FSWs were much more likely to
      report breakage if under 20 years of age (AOR 3.43, p = 0.005); if divorced/
      separated/widowed (AOR 1.52, p = 0.012); if they were regular alcohol users (AOR
      1.63, p = 0.005); if they mostly entertained clients in lodges/rented rooms (AOR
      2.99, p = 0.029) or brothels (AOR 4.77, p = 0.003), compared to street based sex
      workers; if they had ever had anal sex (AOR 2.03, p = 0.006); if the sex worker
      herself (as opposed to the client) applied the condom at last use (AOR 1.90, p <
      0.001); if they were inconsistent condom users (AOR 2.77, p < 0.001); and if they
      had never seen a condom demonstration (AOR 2.37, p < 0.001). CONCLUSIONS: The
      reported incidence of condom breakage was high in this study, and this is a major
      concern for HIV/STI prevention programs, for which condom use is a key prevention
      tool. Younger and more marginalized female sex workers were most vulnerable to
      condom breakage. Special effort is therefore required to seek out such women and
      to provide information and skills on correct condom use. More research is also
      needed on what specific situational parameters might be important in predisposing
      women to condom breakage.

PMID- 22376238
TI  - Painting with biomolecules at the nanoscale: biofunctionalization with tunable
      surface densities.
AB  - We present a generic and flexible method to nanopattern biomolecules on surfaces.
      Carbon-containing nanofeatures are written at variable diameter and spacing by a
      focused electron beam on a poly(ethylene glycol) (PEG)-coated glass substrate.
      Proteins physisorb to the nanofeatures with remarkably high contrast factors of
      more than 1000 compared to the surrounding PEG surfaces. The biological activity
      of model proteins can be retained as shown by decorating avidin spots with
      biotinylated DNA, thereby underscoring the universality of the nano
      biofunctionalized platform for the binding of other biotinylated ligands. In
      addition, biomolecule densities can be tuned over several orders of magnitude
      within the same array, as demonstrated by painting a microscale image with
      nanoscale pixels. We expect that these unique advantages open up entirely new
      ways to design biophysical experiments, for instance, on cells that respond to
      the nanoscale densities of activating molecules.

PMID- 22376239
TI  - Cancer cell differentiation heterogeneity and aggressive behavior in solid
      tumors.
AB  - The differentiation stage of tumors is a central aspect in the histopathological
      classification of solid malignancies. The differentiation stage is strongly
      associated with tumor behavior, and generally an immature tumor is more
      aggressive than the more differentiated counterpart. While this is common
      knowledge in surgical pathology, the contribution of differentiation-related gene
      expression and functions to tumor behavior is often overlooked in the
      experimental, tumor biological setting. The mechanisms by which tumor cell
      differentiation stages are perturbed or affected are poorly explored but have
      recently come into focus with the introduction.of the tumor stem cell concept.
      While developmental biologists view the differentiation as a unidirectional
      event, pathologists and tumor biologists have introduced the concept of
      dedifferentiation to explain phenotypic changes occurring in solid tumors. In
      this review we discuss the impact of the tumor cell differentiation stage as used
      in surgical pathology. We further discuss knowledge gained from exploring the
      molecular basis of the differentiation and dedifferentiation processes in
      neuroblastoma and breast cancer, two tumor forms where the tumor cell
      differentiation concept is used in the clinical diagnostic work and where the
      tumor stem cell theory has been applied.

PMID- 22376240
TI  - PDGF in gliomas: more than just a growth factor?
AB  - Platelet-derived growth factor B (PDGF-B) is a growth factor promoting and
      regulating cell migration, proliferation, and differentiation, involved in both
      developmental processes and in maintaining tissue homeostasis under strict
      regulation. What are the implications of prolonged or uncontrolled growth factor
      signaling in vivo, and when does a growth factor such as PDGF-B become an
      oncogene? Under experimental conditions, PDGF-B induces proliferation and causes
      tumor induction. It is not known whether these tumors are strictly a PDGF-B
      driven proliferation of cells or associated with secondary genetic events such as
      acquired mutations or methylation-mediated gene silencing promoting neoplasia. If
      PDGF-B-driven tumorigenesis was only cellular proliferation, associated changes
      in gene expression would thus be correlated with proliferation and not associated
      with secondary events involved in tumorigenesis and neoplastic transformation
      such as cycle delay, DNA damage response, and cell death. Changes in gene
      expression might be expected to be reversible, as is PDGF-B-driven proliferation
      under normal circumstances. Since PDGF signaling is involved in oligodendrocyte
      progenitor cell differentiation and maintenance, it is likely that PDGF-B
      stimulates proliferation of a pool of cells with that phenotype, and inhibition
      of PDGF-B signaling would result in reduced expression of oligodendrocyte
      associated genes. More importantly, inhibition of PDGF signaling would be
      expected to result in reversion of genes induced by PDGF-B accompanied by a
      decrease in proliferation. However, if PDGF-B-driven tumorigenesis is more than
      simply a proliferation of cells, inhibition of PDGF signaling may not reverse
      gene expression or halt proliferation. These fundamental questions concerning
      PDGF-B as a potential oncogene have not been resolved.

PMID- 22376241
TI  - Medication errors--an enduring problem for children and elderly patients.
AB  - OBJECTIVE: To analyze the types and reasons of medication errors, committed by
      health care professionals, which led to toxicological consultations at the Czech
      Toxicological Information Centre (TIC). METHODS: Inquiries arising from
      medication errors for 2000-2010 were extracted and evaluated from the database of
      the TIC, recording the consultations of poisonings due to drugs, household
      products, plants, and mushrooms. RESULTS: From a total of 44,344 calls concerning
      pharmaceuticals, 215 (0.5%) were denoted by the caller as medication errors; 130
      involved children (90 below 5 years of age) and 85 involved adults (30-60 years
      of age). The most common errors were: improper dosage (60.9%), wrong medication
      (19.3%), or erroneous route of administration (12.9%). The most frequent
      medication errors appeared using drugs affecting the nervous system
      (psycholeptics and antiepileptics), antibiotics, and drugs affecting the
      respiratory system. Nurses administering the drugs were responsible for 43.0%,
      physicians prescribing the drugs for 36.8%, and pharmacists dispensing the drugs
      for 20.2% of the errors. Of 25 patients with severe drug intoxications, 60.0%
      were children under 5 years of age treated with pharmaceuticals affecting the
      CNS, and 28.0% patients over 60 years of age with chronic application of
      theophylline, digoxin, or lithium. CONCLUSIONS: The trend in medication errors
      has remained relatively stable over the past 11 years. The analysis of medication
      errors shows two high-risk categories: children of less than 5 years of age, in
      whom the dose was not correctly adjusted, and elderly people with chronic
      medication and insufficient control of their medication level. Therefore, the
      measures for risk reduction should focus primarily on them.

PMID- 22376242
TI  - Central venous port-related infection in patients with malignant tumors: an
      observational study.
AB  - PURPOSE: We evaluated the characteristics of central venous port (CVP)-related
      infection with microbiological assessments in patients with malignant tumors.
      MATERIALS AND METHODS: In a prospective setting, patients with CVP for the
      treatment of malignant tumors were enrolled in this study. The incidence of CVP
      related infection during three months was determined. Microbiological
      surveillance from skin swab was performed before and after CVP placement.
      RESULTS: Fifty-nine patients were enrolled in this study, and 60 CVPs were
      implanted. Thirty-six (61%) patients had head and neck malignancies. Access route
      was subclavian vein in 43 (71.7%) CVPs and forearm vein in 17 (28.3%). CVP
      related infection was observed in three (5.1%) patients: port-pocket infection in
      one and probable CVP-related infection in two patients, respectively. No
      definitive CVP-related bloodstream infection was observed. Before the placement
      of CVP, colonization at the insertion site was observed in ten subclavian CVP
      patients, while no colonization was observed in the forearm CVP patients. At 1
      and 4 weeks, detection rates of colonization were also higher in subclavian CVP
      patients. No definitive relationship was demonstrated between skin colonization
      and clinical development of CVP-related infection. CONCLUSION: The rate of CVP
      related infection in this prospective evaluation in patients with malignant
      tumors was comparable to previous studies. Colonization of the skin was more
      prominent in the subclavian site than in the forearm site. Although skin
      colonization was not proven to be a risk factor of infection, these results may
      draw attention to the adequate maintenance of CVP. ( TRIAL REGISTRATION:
      UMIN000003664).

PMID- 22376243
TI  - Balearic archipelago: three islands, three beta-thalassemia population patterns.
AB  - The mutation spectrum of 175 beta-thalassemia (beta-thal) carriers, identified in
      pilot carrier screening on 22,713 individuals from Balearic Islands (Spain), is
      reported. The beta(0) CD39 (C>T) mutation is the most frequent (61.1%), followed
      by beta(+) IVS-I-110 (G>A) (12.0%), beta(+) IVS-I-6 (T>C) and beta(0) IVS-1-1
      (G>A) (3.4% both) and eight other rare mutations (2.9-0.6%); with a distinct
      prevalence and distribution between islands. Minorca shows the highest prevalence
      in Iberian populations, with a single mutation, CD39 (C>T), present in most beta
      thal carriers. Ibiza is the only Western Mediterranean population where the most
      frequent beta-thal mutation is IVS-I-110 (G>A). These results can be explained by
      a combination of historical-demographic characteristics together with
      evolutionary forces such as founder effect, genetic drift and probably selection
      by malaria. Knowledge of the mutational spectrum in the Balearic Islands will
      enable to optimize mutation detection strategy for genetic diagnosis of beta-thal
      in these islands.

PMID- 22376249
TI  - Publishing genomic studies: walking the fine line.

PMID- 22376250
TI  - The Clinical and Translational Science Institute at Children's National:
      improving health through pediatric research.

PMID- 22376251
TI  - Discovery proteomics and nonparametric modeling pipeline in the development of a
      candidate biomarker panel for dengue hemorrhagic fever.
AB  - Secondary dengue viral infection can produce capillary leakage associated with
      increased mortality known as dengue hemorrhagic fever (DHF). Because the
      mortality of DHF can be reduced by early detection and intensive support,
      improved methods for its detection are needed. We applied multidimensional
      protein profiling to predict outcomes in a prospective dengue surveillance study
      in South America. Plasma samples taken from initial clinical presentation of
      acute dengue infection were subjected to proteomics analyses using ELISA and a
      recently developed biofluid analysis platform. Demographics, clinical laboratory
      measurements, nine cytokines, and 419 plasma proteins collected at the time of
      initial presentation were compared between the DF and DHF outcomes. Here, the
      subject's gender, clinical parameters, two cytokines, and 42 proteins
      discriminated between the outcomes. These factors were reduced by multivariate
      adaptive regression splines (MARS) that a highly accurate classification model
      based on eight discriminant features with an area under the receiver operator
      curve (AUC) of 0.999. Model analysis indicated that the feature-outcome
      relationship were nonlinear. Although this DHF risk model will need validation in
      a larger cohort, we conclude that approaches to develop predictive biomarker
      models for disease outcome will need to incorporate nonparametric modeling
      approaches.

PMID- 22376252
TI  - Nitric oxide-mediated endothlium-dependent vasodilation is impaired with
      borderline high-LDL cholesterol.
AB  - The experimental aims of this study were to determine: (1) whether nitric oxide
      mediated endothelium-dependent vasodilation is blunted in adult humans with
      borderline high plasma low-density lipoprotein (LDL)-cholesterol compared with
      adults with optimal/near optimal LDL-cholesterol levels; and, if so: (2) whether
      the magnitude of impairment in adults with borderline high LDL-cholesterol is
      similar to adults with high LDL-cholesterol. Forearm blood flow responses to
      intraarterial infusions of acetylcholine and sodium nitroprusside were measured
      in 50 middle-aged (43-64 year) adults: 20 in the optimal/near optimal LDL
      cholesterol range (<130 mg/dL); 20 with borderline high LDL-cholesterol (130-159
      mg/dL); and 10 with high LDL-cholesterol ($160 mg/dL). In addition, blood flow
      responses to acetylcholine were determined in the absence and presence of the
      endothelial nitric oxide synthase inhibitor N(G) -monomethyl-L-arginine (L-NMMA).
      Vasodilation to acetylcholine was ~20% lower (p < 0.05) in the borderline high
      (from 4.3 +/- 0.2 to 12.3 +/- 0.8 mL/100 mL tissue/min) and high (from 4.3 +/-
      0.3 to 12.0 +/- 0.5 mL/100 mL tissue/min) LDL-cholesterol groups compared with
      the optimal/near optimal (from 4.4 +/- 0.2 to 14.5 +/- 0.5 mL/100 mL tissue/min)
      LDL-cholesterol group. L-NMMA significantly reduced (~30%) the vasodilator
      response to acetylcholine in the optimal/near optimal LDL-cholesterol group but
      not the borderline high or high LDL-cholesterol groups. Borderline high LDL
      cholesterol is associated with impaired nitric oxide-mediated endothelium
      dependent vasodilation.

PMID- 22376253
TI  - Bone marrow-derived mesenchymal stem cells up-regulate acetylcholine receptor
      delta subunit through NRG/ErbB3-mediated mitogen-activated protein kinase
      pathway.
AB  - To investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs)
      on the expression of acetylcholine receptor delta subunit (AChRd), the murine
      skeletal muscle cell line Sol8 were grown in DMEM with 20% fetal bovine serum
      added with (conditional medium group) or without (control group) conditional
      medium of BMSC cells for 48 hours. RT-PCR and Western blot were performed to
      access the mRNA and protein levels of AChRd in Sol8 cells, respectively. Western
      blot was used to detect total and phosphorylated protein levels of Ras, Raf-1,
      Mek1/2, and Erk1/2, respectively. NRG-1 antibody added in conditional medium of
      BMSCs, si-ErbB3, and four Ras/Raf/MEK/ERK pathway inhibitors (FTS, Sulindac,
      U0126, and PD98059) were using to investigate the effect of AChRd levels. Our
      studies indicated that expression of AChRd was significantly enhanced in the
      conditional medium group when compared with those in control group and
      phosphorylation of Ras, Raf, Erk1/2 in Sol8 cells was also increased. Although
      gene silencing for ErbB3 gene, adding of NRG-1 antibody in conditional medium of
      BMSCs or treatment of Ras/Raf/MEK/ERK pathway inhibitors can down-regulate
      expression of AChRd and phosphorylation, which suggesting that the
      Ras/Raf/MEK/ERK pathway may be involved in BMSCs-induced expression of AChRd.

PMID- 22376254
TI  - Effects of exercise on microRNA expression in young males peripheral blood
      mononuclear cells.
AB  - MicroRNAs are increasingly seen as targets of drug discovery because they
      influence gene function acting both to silence and subtly modulate protein
      translation. Little is known about effects of dynamic physiological states on
      microRNA regulation in humans. We hypothesized that microRNA expression in
      peripheral blood mononuclear cells (PBMCs) would be affected by brief exercise.
      Twelve young men performed brief bouts of heavy exercise. PBMC microRNA was
      analyzed before and immediately after exercise using the Agilent Human microRNA
      V2 Microarray. Exercise altered expression level of 34 microRNAs (FDR < 0.05).
      Many of them play roles in inflammatory processes (e.g., miR-125b[?], down
      regulated by proinflammatory factor LPS; and miR-132[?], 125b[?] and let-7e[?]
      involved inTLR4 signaling). Using previous exercise data in PBMCs, we linked the
      microRNA changes to specific gene pathways. This analysis identified 12 pathways
      including the TGF-beta and MAPK signaling. We also compared exercise-associated
      microRNA changes in PBMCs with the exercise-associated microRNAs previously
      identified in neutrophils. Nine microRNAs were affected in both PBMCs and
      neutrophils, but only six changed in the same direction. A commonly occurring
      physiologic perturbation, brief heavy exercise, changes microRNA profiles in
      PBMCs, many of which are related to inflammatory processes. The pattern of change
      suggests that exercise differentially influences microRNAs in leukocyte subtypes.

PMID- 22376255
TI  - Digoxin inhibits blood vessel density and HIF-1a expression in castration
      resistant C4-2 xenograft prostate tumors.
AB  - PURPOSE: Recent studies suggest a potential application for digoxin in the
      prevention and/or treatment of prostate cancer. However, the effect of digoxin on
      androgen receptor (AR)-positive prostate tumor in vivo is not clear. This study
      is designed to determine if digoxin can inhibit AR-positive xenograft prostate
      tumors. MATERIALS AND METHODS: Athymic male nude mice were utilized to establish
      subcutaneous C4-2 castration-resistant prostate tumors. The animals were
      castrated and then treated with daily intraperitoneal (i.p.) injection of digoxin
      at 2 mg/kg along with vehicle controls for 7 consecutive days. Tumor growth was
      determined by measuring tumor volume changes, blood vessel density by
      immunostaining of CD31, and cell proliferation by BrdU labeling. The expression
      of HIF-1alpha in C4-2 tumors was measured by Western blot and real-time RT-PCR.
      RESULTS: Digoxin inhibited blood vessel density about fourfold and down-regulated
      HIF-1alpha expression at both mRNA and protein levels. However, digoxin did not
      inhibit C4-2 tumor growth. CONCLUSIONS: Digoxin is a potent inhibitor of HIF
      1alpha signaling pathway and blood vessel formation in C4-2 castration-resistant
      prostate tumors.

PMID- 22376256
TI  - Alterations in skeletal muscle indicators of mitochondrial structure and
      biogenesis in patients with type 2 diabetes and heart failure: effects of
      epicatechin rich cocoa.
AB  - (-)-Epicatechin (Epi), a flavanol in cacao stimulates mitochondrial volume and
      cristae density and protein markers of skeletal muscle (SkM) mitochondrial
      biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are
      diseases associated with defects in SkM mitochondrial structure/function. A study
      was implemented to assess perturbations and to determine the effects of Epi-rich
      cocoa in SkM mitochondrial structure and mediators of biogenesis. Five patients
      with DM2 and stage II/III HF consumed dark chocolate and a beverage containing
      approximately 100 mg of Epi per day for 3 months. We assessed changes in protein
      and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin,
      nNOS, nitric oxide, cGMP, SIRT1, PGC1alpha, Tfam, and mitochondria volume and
      cristae abundance by electron microscopy from SkM. Apparent major losses in
      normal mitochondria structure were observed before treatment. Epi-rich cocoa
      increased protein and/or activity of mediators of biogenesis and cristae
      abundance while not changing mitochondrial volume density. Epi-rich cocoa
      treatment improves SkM mitochondrial structure and in an orchestrated manner,
      increases molecular markers of mitochondrial biogenesis resulting in enhanced
      cristae density. Future controlled studies are warranted using Epi-rich cocoa (or
      pure Epi) to translate improved mitochondrial structure into enhanced cardiac
      and/or SkM muscle function.

PMID- 22376257
TI  - Developing robust, sustainable, implementation systems using rigorous, rapid and
      relevant science.
AB  - BACKGROUND: Current approaches to medical science generally have not resulted in
      rapid, robust integration into feasible, sustainable real world healthcare
      programs and policies. Implementation science risks falling short of expectations
      if it aligns with historical norms. Fundamentally different scientific approaches
      are needed to accelerate such integration. METHODS: We propose that the key goal
      of implementation science should be to study the development, spread and
      sustainability of broadly applicable and practical programs, treatments,
      guidelines, and policies that are contextually relevant and robust across diverse
      settings, delivery staff, and subgroups. We recommend key conceptual and
      methodological characteristics needed to accomplish these goals. RESULTS: The
      methods to produce such advances should be rapid, rigorous, transparent, and
      contextually relevant. We recommend approaches that incorporate a systems
      perspective, investigate generalizability, are transparent, and employ practical
      measures and participatory approaches. CONCLUSIONS: To produce different
      outcomes, we need to think and act differently. Implications of such an
      implementation science approach include fundamental changes that should be
      relevant to Clinical Translational Science Award investigators, comparative
      effectiveness researchers, those interested in pragmatic trials, grant funders,
      and community partners.

PMID- 22376258
TI  - Discovery of a novel circulating biomarker in patients with abdominal aortic
      aneurysm: a pilot study using a proteomic approach.
AB  - Abdominal aortic aneurysm (AAA) is a common condition with high mortality when
      ruptured. Most clinicians agree that small AAAs are best managed by
      ultrasonographic surveillance. However, it has been stated in recent reviews that
      a serum/plasma biomarker that predicts AAA rupture risk would be a powerful tool
      in stratifying patients with small AAA. Identification of such circulating
      biomarkers has been to date unsuccessful. In this study, we used a proteomic
      approach to find new, potential plasma AAA biomarker candidates. Prefractionated
      plasma samples were analyzed by two-dimensional differential in-gel
      electrophoresis to identify differentially expressed proteins between four
      patients with small AAA and four controls without aneurysm. Protein spots that
      differed significantly between patients and controls were selected and identified
      by mass spectrometry. Three protein spots had significantly different expression
      between patients and controls. The most interesting finding was that patients
      with small AAA had increased levels of the enzyme glycosylphosphatidylinositol
      specific phospholipase D (GPI-PLD) compared with the controls without aneurysm.
      In conclusion, by using a proteomic approach, this pilot-study provides evidence
      of GPI-PLD as a novel potential plasma biomarker for AAA.

PMID- 22376259
TI  - Linkage disequilibrium and haplotype analysis of COX-2 and risk of colorectal
      adenoma development.
AB  - Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of
      cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of
      prostaglandins, have been reported to modulate the risk for many human cancers.
      We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of
      13 single nucleotide polymorphisms of the COX-2 gene and examined its
      susceptibility to adenoma development in 72 African American cases and 142
      controls. Results revealed significant variation in LD patterns with consequence
      for adenoma development. Two distinct haplotype blocks were identified; one block
      covered the coding regions of exon 1, introns and a section of the 3'
      unstranslated region (3'-UTR), whereas the second block resided solely in the 3'
      UTR region. A haplotype in block 1 increased the risk of adenoma development by
      threefold (odds ratio [OR]= 2.9, confidence interval [CI]= 1.8-3.7, P= 0.002).
      Regression analysis showed, increase in copies of minor alleles of 6,064(T>C)
      polymorphism associated with increased odds of adenoma development by 80% (OR =
      1.80, CI = 1.09-3.21, P= 0.034), 10,848(G>A) by 84% (OR = 1.84, CI = 1.05-3.23,
      P= 0.034) and 10,935(A>G) by 32% (OR = 1.32, CI = 1.12-3.69, P= 0.036). These
      results support the hypothesis that COX-2 gene might play a role in the etiology
      of colon cancer and warrant further investigation in other cancers. Besides,
      these variations should be taken into account for disease-based association
      studies in which the COX-2 polymorphism is considered as a candidate gene. Clin
      Trans Sci 2012; Volume 5: 60-64.

PMID- 22376260
TI  - Measurement of circulating cell-free DNA in relation to 18F-fluorocholine PET/CT
      imaging in chemotherapy-treated advanced prostate cancer.
AB  - PURPOSE: To examine the effects of chemotherapy on circulating cell-free DNA
      (cfDNA) composition in relation to investigational whole-body measurement of
      tumor activity by fluorine-18 fluorocholine (FCH) positron emission
      tomography/computed tomography (PET/CT) in hormone-refractory prostate cancer
      (HRPC). METHODS: Serial FCH PET/CT scans were performed in eight patients with
      HRPC receiving docetaxel-based chemotherapy. Corresponding serial cfDNA samples
      were characterized by microfluidic electrophoresis, quantified by real-time PCR,
      and compared with PET/CT results. Promoter methylation of two prostate cancer
      associated genes, GSTP1 and RARB2, was assessed by methylation-specific PCR of
      bisulfite-converted cfDNA. RESULTS: Plasma cfDNA concentrations increased
      significantly from 13.3 ng/mL at baseline to 46.8 ng/mL and 50.9 ng/mL after one
      and three treatment cycles, respectively (p= 0.001). GSTP1 and/or RARB2 promoter
      methylation was identified in all pretreatment samples. The appearance of large
      (200 bp-10.4 kb) cfDNA fragments was noted in posttreatment samples along with
      loss of methylation at GSTP1 and/or RARB2. Tumor activity on PET/CT correlated
      with cfDNA concentration (r=-0.50, p= 0.01). Patients meeting criteria for PET
      tumor response had significantly lower pretreatment cfDNA levels than those who
      did not (8.0 vs. 16.4 ng/mL, p= 0.03). CONCLUSIONS: Chemotherapy is associated
      with significant changes in plasma cfDNA content and FCH PET/CT-detected tumor
      activity. These interrelated measures are potential candidate markers of
      therapeutic response in HRPC.

PMID- 22376261
TI  - Evaluating and giving feedback to mentors: new evidence-based approaches.
AB  - A comprehensive mentoring program includes a variety of components. One of the
      most important is the ongoing assessment of and feedback to mentors. Scholars
      need strong active mentors who have the expertise, disposition, motivation,
      skills, and the ability to accept feedback and to adjust their mentoring style.
      Assessing the effectiveness of a given mentor is no easy task. Variability in
      learning needs and academic goals among scholars makes it difficult to develop a
      single evaluation instrument or a standardized procedure for evaluating mentors.
      Scholars, mentors, and program leaders are often reluctant to conduct formal
      evaluations, as there are no commonly accepted measures. The process of giving
      feedback is often difficult and there is limited empirical data on efficacy. This
      article presents a new and innovative six-component approach to mentor evaluation
      that includes the assessment of mentee training and empowerment, peer learning
      and mentor training, scholar advocacy, mentee-mentor expectations, mentor self
      reflection, and mentee evaluation of their mentor.

PMID- 22376262
TI  - Access to core facilities and other research resources provided by the Clinical
      and Translational Science Awards.
AB  - Principal investigators who received Clinical and Translational Science Awards
      created academic homes for biomedical research. They developed program-supported
      websites to offer coordinated access to a range of core facilities and other
      research resources. Visitors to the 60 websites will find at least 170 generic
      services, which this review has categorized in the following seven areas: (1)
      core facilities, (2) biomedical informatics, (3) funding, (4) regulatory
      knowledge and support, (5) biostatistics, epidemiology, research design, and
      ethics, (6) participant and clinical interaction resources, and (7) community
      engagement. In addition, many websites facilitate access to resources with search
      engines, navigators, studios, project development teams, collaboration tools,
      communication systems, and teaching tools. Each of these websites may be accessed
      from a single site, http://www.CTSAcentral.org. The ability to access the
      research resources from 60 of the nation's academic health centers presents a
      novel opportunity for investigators engaged in clinical and translational
      research.

PMID- 22376263
TI  - US Government mandates for clinical and translational research.
AB  - This commentary is germane for clinical and translational researchers. Basic
      scientists may face different obstacles to developing their research careers.
      Over the past several years, the federal government has seen reductions in
      funding for extramural research. It seems that under the adverse economic
      forecasts, things are going to get worse. It might seem logical for the federal
      government to stretch whatever limited resources exist, by asking the
      institutions to cost-share greater fractions of the actual research costs, and as
      an incentive, avoid the imposition of unfunded mandates. But alas, although well
      intended, there have been expensive requirements imposed by the government,
      making it difficult for investigators and institutions to adequately fund and
      conduct their research and for scientific journals to maintain paying
      subscribers. Five prominent and costly changes, which are the focus of this
      commentary are (1) HIPAA, (2) http://ClinicalTrials.Gov, (3) Clinical and
      Translational Science Awards, (4) Upcoming rule changes for IRBs, and (5)
      PubMedCentral, each of which will be discussed in the ensuing paragraphs.

PMID- 22376265
TI  - Enabling innovative translational research in acute kidney injury.
AB  - Acute kidney injury (AKI) is a common, heterogeneous, and detrimental clinical
      condition that has significant attributable morbidity and mortality. Despite
      major advances in understanding the epidemiology, pathogenesis, and outcomes of
      AKI, preventive measures remain inadequate and therapeutic approaches (except for
      renal replacement therapy) have largely proven futile so far. Critical to the
      process of designing rational therapies is translational research, which involves
      the transition between the basic research discoveries and everyday clinical
      applications to prevent, diagnose, and treat human diseases. Progress in
      innovative approaches has been hampered due in part to the reliance on functional
      markers (serum creatinine and blood urea nitrogen) that are neither sensitive nor
      specific to diagnose AKI. This limitation has created a great deal of interest
      and intense investigation to identify a "troponin-like marker" that would
      facilitate recognition of AKI and allow for timely implementation of the precise
      therapeutic agent. The other major obstacle in this field is the diverse and
      complex nature of AKI that involves multiple independent and overlapping
      pathways, making it difficult to cure AKI with a single approach. In this review,
      we will summarize the advances, ongoing studies, and future perspectives in the
      field of translational research of AKI.

PMID- 22376264
TI  - The loss of homeostasis in hemostasis: new approaches in treating and
      understanding acute disseminated intravascular coagulation in critically ill
      patients.
AB  - Disseminated intravascular coagulation (DIC) profoundly increases the morbidity
      and mortality of patients who have sepsis. Both laboratory and clinical research
      advanced the understanding of the biology and pathophysiology of DIC. This, in
      turn, gave rise to improved therapies and patient outcomes. Beginning with a
      stimulus causing disruption of vascular integrity, cytokines and chemokines cause
      activation of systemic coagulation and inflammation. Seemingly paradoxically, the
      interplay between coagulation and inflammation also inhibits endogenous
      anticoagulants, fibrinolytics, and antiinflammatory pathways. The earliest
      documented and best-studied microbial cause of DIC is the lipopolysaccharide
      endotoxin of Gram-negative bacteria. Extensive microvascular thrombi emerge in
      the systemic vasculature due to dysregulation of coagulation. The result of this
      unrestrained, widespread small vessel thromboses multiorgan system failure.
      Consumption of platelets and coagulation factors during this process can lead to
      an elevated risk of hemorrhage. The management of these patients with
      simultaneous hemorrhage and thrombosis is complex and challenging. Definitive
      treatment of DIC, and attenuation of end-organ damage, requires control of the
      inciting cause. Currently, activated protein C is the only approved therapy in
      the United States for sepsis complicated by DIC. Further research is needed in
      this area to improve clinical outcomes for patients with sepsis.

PMID- 22376266
TI  - Molecular analysis of cyst fluid aspiration in the diagnosis and risk assessment
      of cystic lesions of the pancreas.
AB  - Pancreatic cyst detection is increasing largely due to increasing use of cross
      sectional imaging. The management of pancreatic cysts differs for true cysts,
      pseudocysts, mucinous cysts, nonmucinous cysts, and malignant lesions. Depending
      on the setting, diagnostic tests, such as cross-sectional imaging, endoscopic
      ultrasound, cyst fluid chemistry, and cytology, have moderate accuracy in
      characterizing the cyst subtype. Molecular analysis of cyst fluid aspirates has
      shown promise in preliminary studies and may require smaller fluid volumes than
      is needed for carcinoembryonic antigen level and cytology. This article reviews
      published studies in which molecular analysis was performed in the evaluation of
      pancreatic cysts. The molecular studies are compared with the conventional tests.
      Most studies have had moderate sample sizes (16-124) and have characterized a
      high proportion of patients with malignant cysts. Evaluation of molecular
      analysis as a diagnostic tool merits larger prospective trials with long-term
      follow-up of patients who are not sent to surgery. Larger cysts may meet size
      criteria for resection, and it is the smaller cysts for which molecular analysis
      may be of benefit if additional molecular testing results in a change in
      management.

PMID- 22376268
TI  - Prediction of adverse cardiovascular events of noncardiovascular drugs through
      drug-target interaction networks.

PMID- 22376267
TI  - The value proposition of molecular medicine.

PMID- 22376269
TI  - Insertion and substitution chemistry at the boron fourth position in charge
      neutral zwitterionic tripodal tris(methimazolyl)borate ligands.
AB  - A number of new charge-neutral zwitterionic tris(methimazolyl)borate ligands have
      been synthesized, either by substitution of the dimethylamine group in the adduct
      (dimethylamine)tris(methimazolyl)borane (1) or by insertion into its B
      N(dimethylamine) bond by an unsaturated Lewis base. Two new anionic ligands,
      (thiocyanato)tris(methimazolyl)borate and (cyano)tris(methimazolyl)borate, have
      also been accessed by this method.

PMID- 22376270
TI  - Three new alpha-glucosidase inhibitors from guggul, the oleogum resin of
      Commiphora wightii.
AB  - Three new compounds; epi-mukulin, (Z)-Delta(1,2) dehydroguggulsterone and
      Delta(6,7)dehydro-20-hydroxygugglsterone were isolated from the n-hexane-soluble
      fraction (HSF) of the methanol extract of guggul, the oleogum resin of Commiphora
      wightii together with six known compounds: diasesartemin, (+)-epi-magnolin, (+)
      diayangambin, gugglsterol I, (E)-guggulsterone and (Z)-guggulsterone. Their
      structures were elucidated on the basis of different spectroscopic data. alpha
      Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated
      calorimetrically. The HSF showed significant alpha-glucosidase inhibitory effect
      [IC(50) value of 140 ug mL(-1) (p < 0.05)]. Under the assay conditions,
      diasesartemin (IC(50) = 60.6 +/- 0.01 uM) was found to be more potent than the
      positive control, acarbose (IC(50) = 92.94 +/- 0.01 uM); a known alpha
      glucosidase inhibitor (p < 0.05). The IC(50) values of epi-mukulin and (Z)
      guggulsterone were found to be 159.33 and 132.14 uM, respectively. Other
      compounds showed weak alpha-glucosidase inhibitory effects, <30% inhibition of
      the enzyme activity at 0.1 mg mL(-1).

PMID- 22376271
TI  - The health care setting rather than medical speciality impacts on physicians
      adherence to guideline-conform anticoagulation in outpatients with non-valvular
      atrial fibrillation: a cross sectional survey.
AB  - BACKGROUND: In patients with non-valvular atrial fibrillation (NVAF) at high risk
      for stroke guidelines consistently recommend long-term oral anticoagulation (OAC)
      with a vitamin K antagonist. However recommendations remain ambiguous in respect
      to the precise OAC initiation regimens. Based on the clinical observation, that
      the initiation of OAC for NVAF varies considerably in daily practice, we aimed to
      assess the current practice in Switzerland. METHODS: Cross-sectional survey of
      randomly selected general practitioners, internists and cardiologists from
      different health care settings in an urban Swiss region that covers 1.4 million
      inhabitants. The main outcome measures were the preferred antithrombotic
      initiation regimen and long-term treatment in patients with newly diagnosed NVAF
      at high risk for stroke. RESULTS: We received 226 out of 388 (58.2%) surveys.
      Compared to physicians working in a hospital setting (33.6% of respondents)
      physicians in ambulatory care reported more years of experience and claimed lower
      use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long
      term thromboembolic prophylaxis 93.7% of all responders followed current
      recommendation by choosing an OAC. When focussing on guideline-consistent correct
      OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC)
      adherence dropped to 60.6% with hospital physicians demonstrating a significantly
      higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality
      in non-hospital physicians was not related to correct guideline-use. Hospital
      setting remained independently associated with a guideline-conform OAC initiation
      regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians'
      characteristics and clinical experience. Problems when starting an
      anticoagulation treatment were seldom reported (never or seldom accounting for
      94.1% of all responses). CONCLUSIONS: The guideline adherence with respect to OAC
      initiation regimens in NVAF was significantly lower when compared to long-term
      treatment and health care setting rather than medical speciality explained
      guideline-conform OAC initiation. The majority of the physicians did not consider
      the initiation of anticoagulation to be a major obstacle in outpatient care.

PMID- 22376273
TI  - Age-predicted maximal heart rate in healthy subjects: The HUNT fitness study.
AB  - Maximal heart rate (HRmax ) declines substantially with age, but the magnitude
      and possible modifying effect of gender, body composition, and physical activity
      are not fully established. The present study examined the relationship between
      HRmax and age in 3320 healthy men and women within a wide age range using data
      from the HUNT Fitness Study (2007-2008). Subjects were included if a maximal
      effort could be verified during a maximal exercise test. General linear modeling
      was used to determine the effect of age on HRmax . Subsequently, the effects of
      gender, body mass index (BMI), physical activity status, and maximal oxygen
      uptake were examined. Mean predicted HRmax by three former prediction formulas
      were compared with measured HRmax within 10-year age groups. HRmax was
      univariately explained by the formula 211 - 0.64.age (SEE, 10.8), and we found no
      evidence of interaction with gender, physical activity, VO2max level, or BMI
      groups. There were only minor age-adjusted differences in HRmax between these
      groups. Previously suggested prediction equations underestimated measured HRmax
      in subjects older than 30 years. HRmax predicted by age alone may be practically
      convenient for various groups, although a standard error of 10.8 beats/min must
      be taken into account. HRmax in healthy, older subjects and women were higher
      than previously reported.

PMID- 22376277
TI  - Immediate nonfunctional loading of NobelPerfect implants in the anterior dental
      arch in private practice--5-year data.
AB  - BACKGROUND: The concept of scalloped implants to maintain the natural contour of
      the alveolar ridge has been a source of controversy for many years. PURPOSE: This
      study examined the long-term clinical performance of the scalloped NobelPerfect
      implant in a one-stage procedure (immediate loading in the esthetic zone).
      MATERIALS AND METHODS: In 20 patients, immediate prosthetic restorations were
      placed on 31 NobelPerfect implants in a private practice and followed for up to
      78 months. Twenty-one implants were placed immediately after extraction, seven
      implants were placed after osseous consolidation of the extraction sockets, and
      three implants were placed secondary to extended alveolar ridge augmentation
      procedures. All implants were provisionalized on the day of implant placement and
      adjusted to clear all contacts in centric occlusion and during eccentric
      movements. Outcome variables were success rates, marginal bone levels, and pink
      esthetic score (PES) assessed per implant. RESULTS: One implant failed after 1.4
      months. Five patients with six implants in total were scored in the 5-year follow
      up as dropouts. Mean follow-up period of remaining 24 implants was 65 months
      (range, 55-78 months). Cumulative success rates according to the criteria
      specified by Smith and Zarb were 96.8%. Marginal bone levels averaged 1.1 mm
      above the first thread. Mean PES ratings were 10.5 (range, 3-13). CONCLUSIONS:
      Survival rates, marginal bone levels, and esthetic results suggest proof of
      principle for the preservation of the interproximal bony lamella with a scalloped
      implant design in long-term data.

PMID- 22376274
TI  - Recombinant production of the therapeutic peptide lunasin.
AB  - BACKGROUND: Lunasin is a chemopreventive peptide produced in a number of plant
      species. It comprises a helical region with homology to a region of chromatin
      binding proteins, an Arg-Gly-Asp cell adhesion motif and eight aspartic acid
      residues. In vitro studies indicate that lunasin suppresses chemical and oncogene
      driven transformation of mammalian cells. We have explored efficient recombinant
      production of lunasin by exploiting the Clostridium thermocellum CipB cellulose
      binding domain (CBD) as a fusion partner protein. RESULTS: We used a pET28 vector
      to express a CBD-lunasin fusion with a hexahistidine tag and Tobacco Etch Virus
      protease site, to allow protease-mediated release of native lunasin.
      Autoinduction in E. coli BL21 (DE3) Star cells achieved expression of 3.35 g/L of
      CBD-lunasin fusion protein. The final yield of lunasin was 210 mg/L corresponding
      to 32% of the theoretical yield. Purification by cellulose binding and nickel
      affinity chromatography were tested with the latter proving more satisfactory.The
      effects of CBD-lunasin expression on growth and morphology of the E. coli cells
      were examined by light and electron microscopy revealing an altered morphology in
      a proportion of cells. Cell division appeared to be inhibited in these cells
      resulting in elongated, non-septated cells. CONCLUSIONS: The use of CBD as a
      fusion partner gave high protein yields by autoinduction, with lunasin release by
      TEV protease cleavage. With some optimisation this approach could provide a
      potentially valuable route for production of this therapeutic peptide. Over
      expression in the host cells manifest as a cell division defect in a population
      of the cells, presumably mimicking some aspect of the chemopreventive function
      observed in mammalian cells.

PMID- 22376278
TI  - Water-assisted vibrational relaxation of a metal carbonyl complex studied with
      ultrafast 2D-IR.
AB  - Water is capable of assisting exceptionally rapid vibrational relaxation within
      dissolved solute species. Although ultrafast dynamics of metal carbonyl complexes
      have long served as models for vibrational relaxation, all reports to-date have
      investigated nonaqueous solutions due to the insolubility of the vast majority of
      metal carbonyl complexes in water. Using the water-soluble complex
      [RuCl(2)(CO)(3)](2), which belongs to a class known as "carbon monoxide (CO)
      releasing molecules" (CORM), we report the first ultrafast vibrational relaxation
      measurements of a metal carbonyl complex in water and compare this relaxation
      with polar organic solvents, namely, methanol. The vibrational relaxation,
      measured by two-dimensional IR (2D-IR) spectroscopy, is an order of magnitude
      faster in H(2)O (3.12 +/- 0.29 ps) than in methanol (42.25 +/- 3 ps). The
      accelerated relaxation times of the coupled CO units in H(2)O and D(2)O is
      interpreted as resulting from the enhancement of intramolecular relaxation
      pathways through additional coupling induced by the solvent. In addition, the
      vibrational lifetime shows a significant isotope dependence: in D(2)O the
      relaxation time is 4.27 +/- 0.27 ps, a difference of roughly 30%. We interpret
      these measurements in terms of a nonresonant channel primarily arising from
      water's reorientational dynamics, which occur primarily through large angular
      jumps, as well as a resonant transfer of vibrational energy from the carbonyl
      bands to the libration-bend combination band. These measurements indicate that
      metal carbonyls, which are among the strongest IR transitions, are exquisitely
      sensitive to the presence of water and hold promise as IR analogs of EPR spin
      labels.

PMID- 22376279
TI  - Kisspeptins and the control of gonadotrophin secretion.
AB  - Kisspeptins, the peptide products of the KiSS-1 gene, bind to the G protein
      coupled receptor 54 (GPR54). Since 2003, research has revealed the important role
      of kisspeptins in initiating puberty, timing puberty and regulating fertility in
      adulthood. Specific mutations in GPR54 gene cause either delayed/absent puberty
      or precocious puberty. The KiSS-1/GPR54 system stimulates the gonadotrophin
      releasing hormone (GnRH) neurons and is involved in the feedback regulation of
      the HPG axis by gonadal steroids. Different hypothalamic nuclei are involved in
      negative (arcuate nucleus; ARC) and positive (anteroventral periventricular
      nucleus; AVPV) feedback in mice. Continuous administration of kisspeptins down
      regulates the HPG axis. During pregnancy, kisspeptins are secreted from the
      placenta in large amounts and are responsible for the physiological invasion of
      primary human trophoblast. Kisspeptins have been administered to normal male and
      female individuals as well as to women with hypothalamic secondary amenorrhoea.
      In all cases, gonadotrophin secretion was potently stimulated. Kisspeptin
      antagonists have been synthesized to successfully suppress GnRH and gonadotrophin
      release. These agonists and antagonists appear as valuable new tools for
      manipulating the HPG axis and are promising drugs for future treatment. The scope
      of this review highlights the role of kisspeptins in regulating gonadotrophin
      secretion and explores their possible therapeutic use.

PMID- 22376281
TI  - Reducing corruption in a Mexican medical school: impact assessment across two
      cross-sectional surveys.
AB  - BACKGROUND: Corruption pervades educational and other institutions worldwide and
      medical schools are not exempt. Empirical evidence about levels and types of
      corruption in medical schools is sparse. We conducted surveys in 2000 and 2007 in
      the medical school of the Autonomous University of Guerrero in Mexico to document
      student perceptions and experience of corruption and to support the medical
      school to take actions to tackle corruption. METHODS: In both 2000 and 2007
      medical students completed a self-administered questionnaire in the classroom
      without the teacher present. The questionnaire asked about unofficial payments
      for admission to medical school, for passing an examination and for
      administrative procedures. We examined factors related to the experience of
      corruption in multivariate analysis. Focus groups of students discussed the
      quantitative findings. RESULTS: In 2000, 6% of 725 responding students had paid
      unofficially to obtain entry into the medical school; this proportion fell to
      1.6% of the 436 respondents in 2007. In 2000, 15% of students reported having
      paid a bribe to pass an examination, not significantly different from the 18% who
      reported this in 2007. In 2007, students were significantly more likely to have
      bribed a teacher to pass an examination if they were in the fourth year, if they
      had been subjected to sexual harassment or political pressure, and if they had
      been in the university for five years or more. Students resented the need to make
      unofficial payments and suggested tackling the problem by disciplining corrupt
      teachers. The university administration made several changes to the system of
      admissions and examinations in the medical school, based on the findings of the
      2000 survey. CONCLUSION: The fall in the rate of bribery to enter the medical
      school was probably the result of the new admissions system instituted after the
      first survey. Further actions will be necessary to tackle the continuing presence
      of bribery to pass examinations and for administrative procedures. The social
      audit helped to draw attention to corruption and to stimulate actions to tackle
      it.

PMID- 22376284
TI  - Socioeconomical and sociopolitical correlates of interpersonal forgiveness: a
      three-level meta-analysis of the Enright Forgiveness Inventory across 13
      societies.
AB  - We report a meta-analysis on the country-level correlates of the Enright
      Forgiveness Inventory (EFI), to address (1) whether there are differences in
      forgiveness between societies, (2) what society-level context variables can
      account for these differences, and (3) whether conceptual relationships of
      forgiveness found at the individual level can be replicated at the societal
      level. We found sizeable differences between societies that are associated with
      democracy, peacefulness, socioeconomic development, and postmaterialism indices
      of a society. Replicating individual-level results, subjective wellbeing was
      positively related to forgiveness. We discuss the importance of macro-level
      contextual variables for understanding levels of forgiveness. 

PMID- 22376288
TI  - Inhibition of p53 transcriptional activity by human cytomegalovirus UL44.
AB  - Human cytomegalovirus (HCMV) stimulates cellular synthesis of DNA and proteins
      and induces transition of the cell cycle from G(1)  to S and G(2) /M phase, in
      spite of increased amounts of p53 in the infected cells. The immediate early
      protein IE2-86  kDa (IE86) tethers a transcriptional repression domain to p53;
      however, its repression of p53 function is not enough to abrogate the G(1) 
      checkpoint function of p53. Other HCMV proteins that suppress the activity of p53
      were investigated in this study. Of the HCMV proteins that bind to p53 when
      assessed by immunoprecipitation and immunoblot analysis, HCMV UL44 was chosen as
      a candidate protein. It was found that reporter gene containing p53 consensus
      sequence was activated by transfection with wild type p53, but when plasmids of
      p53 with IE86 or UL44 were co-transfected, p53 transcriptional activity was
      decreased to 3-7% of the p53 control in a dose-dependent manner. When the
      deletion mutant of UL44 was co-transected with p53, the carboxyl one-third
      portion of UL44 had little effect on inhibition of p53 transcriptional activity.
      The amount of mRNA p21 was measured in H1299 by real time PCR after transfection
      of the combination of p53 and UL44 vectors and it was found that p21
      transcription by p53 was inhibited dose-dependently by UL44. Increased G0/G1 and
      decreased S phases in p53 wild type-transfected H1299 cells were recovered to the
      level of p53 mutant type-transfected ones by the additional transfection of UL44
      in a dose-dependent manner. In conclusion, the transcriptional activity of p53 is
      suppressed by UL44 as well as by IE86.

PMID- 22376289
TI  - Evaluation of serum creatinine- and cystatin C-based equations for the estimation
      of glomerular filtration rate in a Chinese population.
AB  - OBJECTIVE: This study aimed to evaluate the applicability of a selection of
      glomerular filtration rate (GFR) estimating equations based on serum creatinine
      (SCr) and serum cystatin C in a Chinese population. MATERIAL AND METHODS:
      Estimated GFR values from 10 equations were compared with reference GFR (rGFR)
      from the (99m)Tc-DTPA renal dynamic imaging method. The study enrolled 569
      Chinese participants (41.5% women, 53.5 +/- 16.9 years, range 19-92 years), with
      mean rGFR 74.80 +/- 26.10 (range 9.8-146.8 ml/min/1.73 m(2)). RESULTS: Bland
      Altman analysis illustrated that the 95% agreement limits of all the equations
      surpassed the acceptable tolerance (<60 ml/min/1.73 m(2)), of which the MacIsaac
      equation was the closest one, reaching 71.7 ml/min/1.73 m(2). Linear regression
      analysis also demonstrated a consistent result. When assessed in all
      participants, the accuracy of the six equations reached and exceeded the
      acceptable level (>=70%), of which the Shanghai and MacIsaac equations gained
      more accuracy than others. When compared in subgroups, the Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI), MacIsaac and Cockcroft-Gault (CG) equations
      were optimal for rGFR stages >= 90 ml/min/1.73 m(2), 30-89 ml/min/1.73 m(2) and <
      30 ml/min/1.73 m(2), respectively. CONCLUSION: The results demonstrated that
      further improvement is needed for the selected 10 equations. Not all the cystatin
      C equations were superior to SCr equations. They have their own applicability at
      various GFR levels. At present, the CKD-EPI, MacIsaac and CG equations may be
      applied to evaluate GFR in normal, mild to moderate and severe kidney function,
      respectively.

PMID- 22376290
TI  - Can rural health insurance improve equity in health care utilization? A
      comparison between China and Vietnam.
AB  - INTRODUCTION: Health care financing reforms in both China and Vietnam have
      resulted in greater financial difficulties in accessing health care, especially
      for the rural poor. Both countries have been developing rural health insurance
      for decades. This study aims to evaluate and compare equity in access to health
      care in rural health insurance system in the two countries. METHODS: Household
      survey and qualitative study were conducted in 6 counties in China and 4
      districts in Vietnam. Health insurance policy and its impact on utilization of
      outpatient and inpatient service were analyzed and compared to measure equity in
      access to health care. RESULTS: In China, Health insurance membership had no
      significant impact on outpatient service utilization, while was associated with
      higher utilization of inpatient services, especially for the higher income group.
      Health insurance members in Vietnam had higher utilization rates of both
      outpatient and inpatient services than the non-members, with higher use among the
      lower than higher income groups. Qualitative results show that bureaucratic
      obstacles, low reimbursement rates, and poor service quality were the main
      barriers for members to use health insurance. CONCLUSIONS: China has achieved
      high population coverage rate over a short time period, starting with a limited
      benefit package. However, poor people have less benefit from NCMS in terms of
      health service utilization. Compared to China, Vietnam health insurance system is
      doing better in equity in health service utilization within the health insurance
      members. However with low population coverage, a large proportion of population
      cannot enjoy the health insurance benefit. Mutual learning would help China and
      Vietnam address these challenges, and improve their policy design to promote
      equitable and sustainable health insurance.

PMID- 22376292
TI  - Preparation of dendritic nanostructures of silver and their characterization for
      electroreduction.
AB  - Silver nanostructures of different morphologies including well-defined dendrites
      were synthesized on an Au substrate by a simple surfactant-free method without
      using any template. The morphology of the material was investigated by field
      emission transmission electron microscopy and scanning electron microscopy. The
      crystal nature of the dendritic nanostructure was revealed from their X-ray
      diffraction and electron diffraction patterns. Effects of applied potential,
      electrolysis time, and the solution concentration were studied. The possible
      formation mechanism of the dendritic morphology was discussed from the aspects of
      kinetics and thermodynamics based on the experiment results. The H(2)O(2)
      electroreduction ability of the dendritic materials was characterized. Use of
      silver dendrite-modified electrode as H(2)O(2) sensor was also demonstrated.

PMID- 22376295
TI  - Heading towards the Safer Highways: an assessment of the Avahan prevention
      programme among long distance truck drivers in India.
AB  - BACKGROUND: Using data from two rounds of a cross-sectional, national-level
      survey of long-distance truck drivers, this paper examines the extent and trend
      of sexual risk behavior, prevalence of STI/HIV, and the linkage between exposure
      to HIV prevention programs and safe sex behavior. METHODS: Following the time
      location cluster sampling approach, major transshipment locations covering the
      bulk of India's transport volume along four routes, North-East (NE), North-South
      (NS), North-West (NW) and South-East (SE) were surveyed. First round of the
      survey was conducted in 2007 (sample size 2066) whereas the second round was
      undertaken in 2009-2010 (sample size 2085). Long distance truck drivers were
      interviewed about their sexual behaviors, condom use practices, exposure to
      different HIV prevention interventions, and tested for HIV, reactive syphilis
      serology, Neiserria gonorrhoeae and Chlamydia trachomatis. The key variable of
      this evaluation study - exposure to HIV prevention interventions was divided into
      three categories - no exposure, less intensive exposure and intensive exposure.
      Data were analyzed using multiple logistic regression methods to understand the
      relationship between risk behavior and exposure to intervention and between
      program exposure and condom use. RESULTS: The proportion of truckers exposed to
      HIV prevention interventions has increased over time with much significant
      increase in the intensive exposure across all the four routes (NE: from 14.9% to
      28%, P < 0.01; NS: from 20.9% to 38.1%; NW: 11.5% to 39.5%, P < 0.01; SE: 4.7% to
      9.7%, P <0.05). Overall, the consistent condom use in sex with non-regular female
      partners too has increased over the time (paid female partners: from 67.1% to
      73.2%, P <0.05; non-paid female partners: from 17.9% to 37.1%, P <0.05). At the
      aggregate level, the proportion tested HIV positive has declined from 3.2% to
      2.5% in (p<0.10) and proportion tested positive for Syphilis too has reduced from
      3.2% to 1.7% (p<0.05). Truckers who had sex with paid female partners (men at
      risk) were significantly more likely to get exposed to intensive program (aOR:
      2.6, 95%CI 1.9-3.4) as compared to those who did not have sex with paid partners.
      Truckers who had sex with paid partners and exposed to intervention program were
      more likely to use condoms consistently (aOR: 2.1, 95% CI 1.2-3.7). The
      consistent condom use among respondents who travel through states with targeted
      interventions towards female sex workers was higher than those who travel through
      states with less intensive program among FSWs. CONCLUSIONS: These evaluation
      study results highlight the ability of intensive program to reach truckers who
      have sex outside marriage with HIV prevention interventions and promote safe sex
      behaviors among them. Truckers who practice safe sex behaviors with an exposure
      to intensive program are less likely to suffer from STIs and HIV, which has
      implications for HIV prevention program with truckers' population in India and
      elsewhere. The simultaneous targeted interventions among female sex workers
      appeared to have contributed to safe sexual practices among truckers.

PMID- 22376300
TI  - A (T-P) phase diagram of hydrogen storage on (N4C3H)6Li6.
AB  - Temperature-pressure phase diagrams are generated through the study of hydrogen
      adsorption on the (N(4)C(3)H)(6)Li(6) cluster at the B3LYP/6-31+G(d) level of
      theory. The possibility of hydrogen storage in an associated 3D functional
      material is also explored. Electronic structure calculations are performed to
      generate temperature-pressure phase diagrams so that the temperature-pressure
      zones are identified where the Gibbs free energy change associated with the
      hydrogen adsorption process on (N(4)C(3)H)(6)Li(6) cluster becomes negative and
      hence thermodynamically favorable. Both adsorption and desorption processes are
      likely to be kinetically feasible as well.

PMID- 22376298
TI  - How amidoximate binds the uranyl cation.
AB  - This study identifies how the amidoximate anion, AO, interacts with the uranyl
      cation, UO(2)(2+). Density functional theory calculations have been used to
      evaluate possible binding motifs in a series of [UO(2)(AO)(x)(OH(2))(y)](2-x) (x
      = 1-3) complexes. These motifs include monodentate binding to either the oxygen
      or the nitrogen atom of the oxime group, bidentate chelation involving the oxime
      oxygen atom and the amide nitrogen atom, and eta(2) binding with the N-O bond.
      The theoretical results establish the eta(2) motif to be the most stable form.
      This prediction is confirmed by single-crystal X-ray diffraction of UO(2)(2+)
      complexes with acetamidoxime and benzamidoxime anions.

PMID- 22376301
TI  - A rare Hb H disease due to the - -(SEA) and 16.6 kb alpha-thalassemia-2
      deletions.
AB  - A large deletional alpha-thalassemia-2 (alpha-thal-2) allele was identified in a
      Thai woman with Hb H disease. The proband has alpha-thal-1 (SEA type) in
      conjunction with a 16.6 kb deletion affecting the alpha2-globin allele. The
      proband had severe anemia and required a blood transfusion during puerperium.

PMID- 22376304
TI  - Excitatory effect of propiverine hydrochloride on urethral activity in rats.
AB  - OBJECTIVES: To investigate the effects of the antimuscarinic agent, propiverine,
      on the bladder and urethra in rats. METHODS: A total of 54 female rats were given
      propiverine, imidafenacin (an antimuscarinic agent), or distilled water by gavage
      once or twice daily. After 2 weeks, bladder and urethral activity were recorded
      under urethane anesthesia. In the propiverine group, the changes of bladder and
      urethral activity before and after intravenous injection of alpha(1) -adrenergic
      antagonists (prazosin, silodosin and naftopidil) were also recorded. Furthermore,
      the leak point pressure after electrical stimulation of abdominal wall muscles
      was measured in rats with vaginal distension from the control and propiverine
      groups. RESULTS: Intravesical baseline pressure was significantly lower in the
      propiverine and imidafenacin groups compared with the control group, whereas the
      urethral baseline pressure was significantly higher in the propiverine group
      compared with the control or imidafenacin groups. Intravenous injection of
      prazosin (an alpha(1) -receptor antagonist) significantly decreased the urethral
      baseline pressure in both of the propiverine and control groups. Intravenous
      injection of silodosin and naftopidil (alpha(1A) - and alpha(1D) -receptor
      antagonists, respectively) significantly decreased the maximum contraction
      pressure and the urethral baseline pressure in the propiverine group. The leak
      point pressure of the propiverine group was significantly higher than that of the
      control group. CONCLUSIONS: An increase of catecholamines after propiverine
      administration might activate smooth muscle of the proximal urethra via alpha(1A)
      - and alpha(1D) -adrenergic receptors, as well as activating urethral and pelvic
      floor striated muscle via the spinal motoneurons.

PMID- 22376306
TI  - Morphologies near cloud point in aqueous ionic surfactant: scattering and NMR
      studies.
AB  - Clouding phenomenon in ionic surfactant solution is fairly a new addition to the
      conventional phenomenon observed with nonionic counterpart. Various scattering
      and spectroscopic techniques, dynamic light scattering (DLS), small angle neutron
      scattering (SANS), and nuclear magnetic resonance (NMR), have been used to draw
      information regarding the aggregate morphologies (formed by an ionic surfactant,
      tetra-n-butylammonium dodecylsulphate, TBADS) when the surfactant solution passes
      through the cloud point (CP). DLS measurements have shown that two morphologies
      are present when the system approaches the CP. The data revealed that individual
      micelles (~5 nm) convert to giant aggregates (~500 nm) over the range of
      temperature including the CP. SANS experiments have been performed to draw the
      information regarding individual micellar fraction below and above the CP. NMR
      spectra at different temperatures have been collected for TBADS solution. The
      broadening and the downfield shift of -N-CH(2) and -O-CH(2) proton peaks support
      the micellar growth as the sample was heated. The above peaks show splitting
      (into two each) confirming the presence of two morphologies around the CP. It is
      noted that conversion of only a small fraction of individual micelles is
      responsible for the clouding.

PMID- 22376313
TI  - Errorless learning and rehabilitation of language and memory impairments.

PMID- 22376314
TI  - A direct comparison of errorless and errorful therapy for object name relearning
      in Alzheimer's disease.
AB  - Developing rehabilitation techniques to combat cognitive decline is a key goal of
      healthcare strategies aimed at promoting increased longevity and better quality
      of life for individuals with Alzheimer's disease (AD). In AD, problems with
      episodic memory and word-finding greatly affect everyday life and, as such, these
      symptoms provide a clear clinical target for therapeutic interventions. Errorless
      learning (EL) has been proposed as a particularly effective technique for
      relearning in individuals with memory dysfunction, including AD. However, EL
      learning has rarely been directly contrasted with other more traditional trial
      and-error techniques (errorful learning or EF) in individuals with AD, especially
      in the context of alleviating word-finding problems. In the current study, we
      directly contrasted the therapeutic gains of an EL learning paradigm (consisting
      of reading/repetition of object names) with an EF learning technique (comprised
      of phonemic/orthographic cueing) in eight mild to moderate AD patients with
      pronounced anomia. Both techniques were administered concurrently in sessions run
      twice a week over a five-week period. Therapeutic gains were assessed at one week
      and five weeks post-intervention using confrontation naming. Our results suggest
      that, both at the group and individual patient level, EL and EF techniques were
      equally effective. Correlational analyses of overall therapy gains and background
      assessments of patient neuropsychology revealed that individuals with better
      scores on measures of semantic memory, pre-intervention naming, and recognition
      memory demonstrated larger therapy gains. No individual patient showed a
      significant advantage for EL over EF learning, however, for patients that showed
      a numerical advantage in this direction. These results suggest that either EL or
      EF therapy can be used to alleviate word-finding problems in AD.

PMID- 22376315
TI  - Overview and ways forward for future research.
AB  - This Special Issue of Neuropsychological Rehabilitation on errorless learning in
      rehabilitation of language and memory impairments includes one review and six
      empirical studies, which present new clinical findings evaluating the
      effectiveness of errorless learning as an intervention method for people whose
      symptoms stem from different neurological aetiologies. These studies delineate
      some of the critical theoretical-clinical issues through which we might optimise
      learning and rehabilitative efforts more fully.

PMID- 22376316
TI  - Population weighted raster maps can communicate findings of social audits:
      examples from three continents.
AB  - BACKGROUND: Maps can portray trends, patterns, and spatial differences that might
      be overlooked in tabular data and are now widely used in health research. Little
      has been reported about the process of using maps to communicate epidemiological
      findings. METHOD: Population weighted raster maps show colour changes over the
      study area. Similar to the rasters of barometric pressure in a weather map, data
      are the health occurrence--a peak on the map represents a higher value of the
      indicator in question. The population relevance of each sentinel site, as
      determined in the stratified last stage random sample, combines with geography
      (inverse-distance weighting) to provide a population-weighted extension of each
      colour. This transforms the map to show population space rather than simply
      geographic space. RESULTS: Maps allowed discussion of strategies to reduce
      violence against women in a context of political sensitivity about quoting
      summary indicator figures. Time-series maps showed planners how experiences of
      health services had deteriorated despite a reform programme; where in a country
      HIV risk behaviours were improving; and how knowledge of an economic development
      programme quickly fell off across a region. Change maps highlighted where
      indicators were improving and where they were deteriorating. Maps of potential
      impact of interventions, based on multivariate modelling, displayed how partial
      and full implementation of programmes could improve outcomes across a country.
      Scale depends on context. To support local planning, district maps or local
      government authority maps of health indicators were more useful than national
      maps; but multinational maps of outcomes were more useful for regional
      institutions. Mapping was useful to illustrate in which districts enrolment in
      religious schools--a rare occurrence--was more prevalent. CONCLUSIONS: Population
      weighted raster maps can present social audit findings in an accessible and
      compelling way, increasing the use of evidence by planners with limited numeracy
      skills or little time to look at evidence. Maps complement epidemiological
      analysis, but they are not a substitute. Much less do they substitute for
      rigorous epidemiological designs, like randomised controlled trials.

PMID- 22376320
TI  - Evaluating AVAHAN's design, implementation and impact: lessons learned for the
      HIV Prevention Community.

PMID- 22376324
TI  - Superior performance of range-separated hybrid functionals for describing sigma*
      <- sigma UV-vis signatures of three-electron two-center anions.
AB  - We assess the efficiency of density functionals for the description of UV-vis
      signatures of temporary anions featuring a three-electron two-center bond, along
      a representative set of systems ranging from (pseudo)dihalides to disulfide
      radical anions (dimethyl disulfide and lipoate). While BH&HLYP and B3LYP have
      been predominantly applied to perform such simulations so far, we outline the
      significantly improved performance of several recently proposed functionals,
      including range-separated hybrids for the computation of these specific vertical
      transitions.

PMID- 22376353
TI  - Clustering and meso-level variables in cross-sectional surveys: an example of
      food aid during the Bosnian crisis.
AB  - BACKGROUND: Focus groups, rapid assessment procedures, key informant interviews
      and institutional reviews of local health services provide valuable insights on
      health service resources and performance. A long-standing challenge of health
      planning is to combine this sort of qualitative evidence in a unified analysis
      with quantitative evidence from household surveys. A particular challenge in this
      regard is to take account of the neighbourhood or clustering effects, recognising
      that these can be informative or incidental. METHODS: An example of food aid and
      food sufficiency from the Bosnian emergency (1995-96) illustrates two Lamothe
      cluster-adjustments of the Mantel Haenszel (MH) procedure, one assuming a fixed
      odds ratio and the other allowing for informative clustering by not assuming a
      fixed odds ratio. We compared these with conventional generalised estimating
      equations and a generalised linear mixed (GLMM) model, using a Laplace
      adjustment. RESULTS: The MH adjustment assuming incidental clustering generated a
      final model very similar to GEE. The adjustment that does not assume a fixed odds
      ratio produced a final multivariate model and effect sizes very similar to GLMM.
      DISCUSSION: In medium or large data sets with stratified last stage random
      sampling, the cluster adjusted MH is substantially more conservative than the
      naive MH computation. In the example of food aid in the Bosnian crisis, the
      cluster adjusted MH that does not assume a fixed odds ratio produced similar
      results to the GLMM, which identified informative clustering.

PMID- 22376364
TI  - Genetic diversity, population structure and subdivision of local Balkan pig
      breeds in Austria, Croatia, Serbia and Bosnia-Herzegovina and its practical value
      in conservation programs.
AB  - BACKGROUND: At present the Croatian Turopolje pig population comprises about 157
      breeding animals. In Austria, 324 Turopolje pigs originating from six Croatian
      founder animals are registered. Multiple bottlenecks have occurred in this
      population, one major one rather recently and several more older and moderate
      ones. In addition, it has been subdivided into three subpopulations, one in
      Austria and two in Croatia, with restricted gene flow. These specificities
      explain the delicate situation of this endangered Croatian lard-type pig breed.
      METHODS: In order to identify candidate breeding animals or gene pools for future
      conservation breeding programs, we studied the genetic diversity and population
      structure of this breed using microsatellite data from 197 individuals belonging
      to five different breeds. RESULTS: The genetic diversity of the Turopolje pig is
      dramatically low with observed heterozygosities values ranging from 0.38 to 0.57.
      Split into three populations since 1994, two genetic clusters could be
      identified: one highly conserved Croatian gene pool in Turopoljski Lug and
      the"Posavina" gene pool mainly present in the Austrian population. The second
      Croatian subpopulation in Lonjsko Polje in the Posavina region shows a constant
      gene flow from the Turopoljski Lug animals. CONCLUSIONS: One practical conclusion
      is that it is necessary to develop a "Posavina" boar line to preserve the
      "Posavina" gene pool and constitute a corresponding population in Croatia.
      Animals of the highly inbred herd in Turopoljski Lug should not be crossed with
      animals of other populations since they represent a specific phenotype-genotype
      combination. However to increase the genetic diversity of this herd, a program to
      optimize its sex ratio should be carried out, as was done in the Austrian
      population where the level of heterozygosity has remained moderate despite its
      heavy bottleneck in 1994.

PMID- 22376386
TI  - Proof of impact and pipeline planning: directions and challenges for social audit
      in the health sector.
AB  - Social audits are typically observational studies, combining qualitative and
      quantitative uptake of evidence with consultative interpretation of results. This
      often falters on issues of causality because their cross-sectional design limits
      interpretation of time relations and separation out of other indirect
      associations.Social audits drawing on methods of randomised controlled cluster
      trials (RCCT) allow more certainty about causality. Randomisation means that
      exposure occurs independently of all events that precede it--it converts
      potential confounders and other covariates into random differences. In 2008, CIET
      social audits introduced randomisation of the knowledge translation component
      with subsequent measurement of impact in the changes introduced. This "proof of
      impact" generates an additional layer of evidence in a cost-effective way,
      providing implementation-ready solutions for planners.Pipeline planning is a
      social audit that incorporates stepped wedge RCCTs. From a listing of
      districts/communities as a sampling frame, individual entities (communities,
      towns, districts) are randomly assigned to waves of intervention. Measurement of
      the impact takes advantage of the delay occasioned by the reality that there are
      insufficient resources to implement everywhere at the same time. The impact in
      the first wave contrasts with the second wave, which in turn contrasts with a
      third wave, and so on until all have received the intervention. Provided care is
      taken to achieve reasonable balance in the random allocation of communities,
      towns or districts to the waves, the resulting analysis can be
      straightforward.Where there is sufficient management interest in and commitment
      to evidence, pipeline planning can be integrated in the roll-out of programmes
      where real time information can improve the pipeline. Not all interventions can
      be randomly allocated, however, and random differences can still distort
      measurement. Other issues include contamination of the subsequent waves,
      ambiguity of indicators, "participant effects" that result from lack of blinding
      and lack of placebos, ethics and, not least important, the skills to do pipeline
      planning correctly.

PMID- 22376744
TI  - Collective excitations on a surface of topological insulator.
AB  - We study collective excitations in a helical electron liquid on a surface of
      three-dimensional topological insulator. Electron in helical liquid obeys Dirac
      like equation for massless particles and direction of its spin is strictly
      determined by its momentum. Due to this spin-momentum locking, collective
      excitations in the system manifest themselves as coupled charge- and spin-density
      waves. We develop quantum field-theoretical description of spin-plasmons in
      helical liquid and study their properties and internal structure. Value of spin
      polarization arising in the system with excited spin-plasmons is calculated. We
      also consider the scattering of spin-plasmons on magnetic and nonmagnetic
      impurities and external potentials, and show that the scattering occurs mainly
      into two side lobes. Analogies with Dirac electron gas in graphene are
      discussed.PACS: 73.20.Mf; 73.22.Lp; 75.25.Dk.

PMID- 22376375
TI  - CONNECT for quality: protocol of a cluster randomized controlled trial to improve
      fall prevention in nursing homes.
AB  - BACKGROUND: Quality improvement (QI) programs focused on mastery of content by
      individual staff members are the current standard to improve resident outcomes in
      nursing homes. However, complexity science suggests that learning is a social
      process that occurs within the context of relationships and interactions among
      individuals. Thus, QI programs will not result in optimal changes in staff
      behavior unless the context for social learning is present. Accordingly, we
      developed CONNECT, an intervention to foster systematic use of management
      practices, which we propose will enhance effectiveness of a nursing home Falls QI
      program by strengthening the staff-to-staff interactions necessary for clinical
      problem-solving about complex problems such as falls. The study aims are to
      compare the impact of the CONNECT intervention, plus a falls reduction QI
      intervention (CONNECT + FALLS), to the falls reduction QI intervention alone
      (FALLS), on fall-related process measures, fall rates, and staff interaction
      measures. METHODS/DESIGN: Sixteen nursing homes will be randomized to one of two
      study arms, CONNECT + FALLS or FALLS alone. Subjects (staff and residents) are
      clustered within nursing homes because the intervention addresses social
      processes and thus must be delivered within the social context, rather than to
      individuals. Nursing homes randomized to CONNECT + FALLS will receive three
      months of CONNECT first, followed by three months of FALLS. Nursing homes
      randomized to FALLS alone receive three months of FALLs QI and are offered
      CONNECT after data collection is completed. Complexity science measures, which
      reflect staff perceptions of communication, safety climate, and care quality,
      will be collected from staff at baseline, three months after, and six months
      after baseline to evaluate immediate and sustained impacts. FALLS measures
      including quality indicators (process measures) and fall rates will be collected
      for the six months prior to baseline and the six months after the end of the
      intervention. Analysis will use a three-level mixed model. DISCUSSION: By
      focusing on improving local interactions, CONNECT is expected to maximize staff's
      ability to implement content learned in a falls QI program and integrate it into
      knowledge and action. Our previous pilot work shows that CONNECT is feasible,
      acceptable and appropriate. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00636675.

PMID- 22376768
TI  - A top-down approach to classify enzyme functional classes and sub-classes using
      random forest.
AB  - Advancements in sequencing technologies have witnessed an exponential rise in
      the number of newly found enzymes. Enzymes are proteins that catalyze bio
      chemical reactions and play an important role in metabolic pathways. Commonly,
      function of such enzymes is determined by experiments that can be time consuming
      and costly. Hence, a need for a computing method is felt that can distinguish
      protein enzyme sequences from those of non-enzymes and reliably predict the
      function of the former. To address this problem, approaches that cluster enzymes
      based on their sequence and structural similarity have been presented. But, these
      approaches are known to fail for proteins that perform the same function and are
      dissimilar in their sequence and structure. In this article, we present a
      supervised machine learning model to predict the function class and sub-class of
      enzymes based on a set of 73 sequence-derived features. The functional classes
      are as defined by International Union of Biochemistry and Molecular Biology.
      Using an efficient data mining algorithm called random forest, we construct a top
      down three layer model where the top layer classifies a query protein sequence as
      an enzyme or non-enzyme, the second layer predicts the main function class and
      bottom layer further predicts the sub-function class. The model reported overall
      classification accuracy of 94.87% for the first level, 87.7% for the second, and
      84.25% for the bottom level. Our results compare very well with existing methods,
      and in many cases report better performance. Using feature selection methods, we
      have shown the biological relevance of a few of the top rank attributes.

PMID- 22376791
TI  - Rest versus exercise as treatment for patients with low back pain and Modic
      changes. A randomized controlled clinical trial.
AB  - BACKGROUND: Clinical experience suggests that many patients with Modic changes
      have relatively severe and persistent low back pain (LBP), which typically
      appears to be resistant to treatment. Exercise therapy is the recommended
      treatment for chronic LBP, however, due to their underlying pathology, Modic
      changes might be a diagnostic subgroup that does not benefit from exercise. The
      objective of this study was to compare the current state-of-the art treatment
      approach (exercise and staying active) with a new approach (load reduction and
      daily rest) for people with Modic changes using a randomized controlled trial
      design. METHODS: Participants were patients from an outpatient clinic with
      persistent LBP and Modic changes. They were allocated using minimization to
      either rest therapy for 10 weeks with a recommendation to rest for two hours
      daily and the option of using a flexible lumbar belt or exercise therapy once a
      week for 10 weeks. Follow-up was at 10 weeks after recruitment and 52 weeks after
      intervention and the clinical outcome measures were pain, disability, general
      health and global assessment, supplemented by weekly information on low back
      problems and sick leave measured by short text message (SMS) tracking. RESULTS:
      In total, 100 patients were included in the study. Data on 87 patients at 10
      weeks and 96 patients at one-year follow-up were available and were used in the
      intention-to-treat analysis. No statistically significant differences were found
      between the two intervention groups on any outcome. CONCLUSIONS: No differences
      were found between the two treatment approaches, 'rest and reduced load' and
      'exercise and staying active', in patients with persistent LBP and Modic changes.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00454792.

PMID- 22376892
TI  - A new method of lower extremity immobilization in radiotherapy.
AB  - We developed a new method for immobilization of the fix lower extremities by
      using a thermoplastic mask, a carbon fiber base plate, a customized headrest, and
      an adjustable angle holder. The lower extremities of 11 patients with lower
      extremity tumors were immobilized by this method. CT simulation was performed for
      each patient. For all 11 patients, the device fit was suitable and comfortable
      and had good reproducibility, which was proven in daily radiotherapy.

PMID- 22376902
TI  - Evaluation of a combined triple method to detect causative HPV in oral and
      oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR
      HPV-DNA, and In Situ Hybridization.
AB  - BACKGROUND: Recent emerging evidences identify Human Papillomavirus (HPV) related
      Head and Neck squamous cell carcinomas (HN-SCCs) as a separate subgroup among
      Head and Neck Cancers with different epidemiology, histopathological
      characteristics, therapeutic response to chemo-radiation treatment and clinical
      outcome. However, there is not a worldwide consensus on the methods to be used in
      clinical practice. The endpoint of this study was to demonstrate the reliability
      of a triple method which combines evaluation of: 1. p16 protein expression by
      immunohistochemistry (p16-IHC); 2. HPV-DNA genotyping by consensus HPV-DNA PCR
      methods (Consensus PCR); and 3 viral integration into the host by in situ
      hybridization method (ISH). This triple method has been applied to HN-SCC
      originated from oral cavity (OSCC) and oropharynx (OPSCC), the two anatomical
      sites in which high risk (HR) HPVs have been clearly implicated as etiologic
      factors. Methylation-Specific PCR (MSP) was performed to study inactivation of
      p16-CDKN2a locus by epigenetic events. Reliability of multiple methods was
      measured by Kappa statistics. RESULTS: All the HN-SCCs confirmed HPV positive by
      PCR and/or ISH were also p16 positive by IHC, with the latter showing a very high
      level of sensitivity as single test (100% in both OSCC and OPSCC) but lower
      specificity level (74% in OSCC and 93% in OPSCC).Concordance analysis between ISH
      and Consensus PCR showed a faint agreement in OPSCC (kappa = 0.38) and a moderate
      agreement in OSCC (kappa = 0.44). Furthermore, the addition of double positive
      score (ISHpositive and Consensus PCR positive) increased significantly the
      specificity of HR-HPV detection on formalin-fixed paraffin embedded (FFPE)
      samples (100% in OSCC and 78.5% in OPSCC), but reduced the sensitivity (33% in
      OSCC and 60% in OPSCC). The significant reduction of sensitivity by the double
      method was compensated by a very high sensitivity of p16-IHC detection in the
      triple approach. CONCLUSIONS: Although HR-HPVs detection is of utmost importance
      in clinical settings for the Head and Neck Cancer patients, there is no consensus
      on which to consider the 'golden standard' among the numerous detection methods
      available either as single test or combinations. Until recently, quantitative E6
      RNA PCR has been considered the 'golden standard' since it was demonstrated to
      have very high accuracy level and very high statistical significance associated
      with prognostic parameters. In contrast, quantitative E6 DNA PCR has proven to
      have very high level of accuracy but lesser prognostic association with clinical
      outcome than the HPV E6 oncoprotein RNA PCR. However, although it is
      theoretically possible to perform quantitative PCR detection methods also on FFPE
      samples, they reach the maximum of accuracy on fresh frozen tissue. Furthermore,
      worldwide diagnostic laboratories have not all the same ability to analyze
      simultaneously both FFPE and fresh tissues with these quantitative molecular
      detection methods. Therefore, in the current clinical practice a p16-IHC test is
      considered as sufficient for HPV diagnostic in accordance with the recently
      published Head and Neck Cancer international guidelines. Although p16-IHC may
      serve as a good prognostic indicator, our study clearly demonstrated that it is
      not satisfactory when used exclusively as the only HPV detecting method. Adding
      ISH, although known as less sensitive than PCR-based detection methods, has the
      advantage to preserve the morphological context of HPV-DNA signals in FFPE
      samples and, thus increase the overall specificity of p16/Consensus PCR
      combination tests.

PMID- 22376909
TI  - Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to
      migratory paths from ganglionic eminence to cortical destinations.
AB  - BACKGROUND: Cortical GABAergic interneurons (INs) are generated in the medial
      ganglionic eminence (MGE) and migrate tangentially into cortex. Because most, if
      not all, migrating MGE-derived INs express the neuregulin (NRG) receptor, ErbB4,
      we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through
      ventral telencephalon (vTel) and within cortex. RESULTS: During IN migration, NRG
      expression domains and distributions of ErbB4-expressing, MGE-derived INs are
      complementary with minimal overlap, both in vTel and cortex. In wild-type mice,
      within fields of NRG expression, these INs are focused at positions of low or
      absent NRG expression. However, in ErbB4-/- HER4(heart) mutant mice in which INs
      lack ErbB4, these complementary patterns are degraded with considerable overlap
      evident between IN distribution and NRG expression domains. These findings
      suggest that NRGs are repellents for migrating ErbB4-expressing INs, a function
      supported by in vitro and in vivo experiments. First, in collagen co-cultures,
      MGE-derived cells preferentially migrate away from a source of secreted NRGs.
      Second, cells migrating from wild-type MGE explants on living forebrain slices
      from wild-type embryonic mice tend to avoid endogenous NRG expression domains,
      whereas this avoidance behavior is not exhibited by ErbB4-deficient cells
      migrating from MGE explants and instead they have a radial pattern with a more
      uniform distribution. Third, ectopic NRG expression in the IN migration pathway
      produced by in utero electroporation blocks IN migration and results in cortex
      distal to the blockade being largely devoid of INs. Finally, fewer INs reach
      cortex in ErbB4 mutants, indicating that NRG-ErbB4 signaling is required for
      directing IN migration from the MGE to cortex. CONCLUSIONS: Our results show that
      NRGs act as repellents for migrating ErbB4-expressing, MGE-derived GABAergic INs
      and that the patterned expression of NRGs funnels INs as they migrate from the
      MGE to their cortical destinations.

PMID- 22376935
TI  - Effectiveness of Chinese herbal medicine in treating liver fibrosis: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The studies on the effectiveness of Chinese herbal medicines (CHM) in
      treating liver fibrosis (LF) were not consistent. This study aims to
      systematically review the effectiveness of CHM on treating LF patients. METHODS:
      Databases including MEDLINE, AMED, EMBASE, The Cochrane Central Register of
      Controlled Trials, China National Knowledge Infrastructure, TCMOnline, Chinese
      Biomedical Literature Database, and Chinese Medical Current Contents were
      searched up to March 2011. Randomized controlled trials (RCTs) involving LF
      patients receiving CHM, Western medicine, combined CHM and Western medicine
      compared with placebo, Western medicine or no intervention were included. LF
      markers including serum hyaluronic acid (HA), laminin (LN), procollagen type III
      (PC-III), type IV collagen (IV-C), matrix metalloproteinase (MMP), and tissue
      inhibitors of metalloproteinase (TIMP) were measured as primary outcomes. Liver
      biochemistry, including alanine aminotransferase (ALT) and aspartarte
      aminotransferase (AST), and improvement of related clinical symptoms were
      measured as secondary outcomes. Risk of bias of allocation sequence, allocation
      concealment, blinding, incomplete outcome data, selective outcome reporting, and
      other biases were assessed. RESULTS: Twenty-three RCTs with 2123 participants
      were analyzed in subgroups of types of comparison and study quality. Fifteen
      studies were graded as good quality. CHM alone and combined with Western medicine
      showed significant improvements in HA, LN, PC-III and IV-C compared with Western
      medicine alone. However, there were no significant differences observed between
      CHM and placebo treatments. CONCLUSION: The current inconclusive results in
      determining the effectiveness of CHM treatment on LF, due to the poor
      methodological quality and high heterogeneity of the studies, suggests that large
      RCTs using standardized Chinese medicine syndrome diagnosis and CHM formulae with
      longer follow-up are required for further evaluation.

PMID- 22376948
TI  - Epidemiological aspects of rheumatoid arthritis patients affected by oral
      bisphosphonate-related osteonecrosis of the jaws.
AB  - This literature review aims to evaluate the epidemiologic profile of patients
      with rheumatoid arthritis (RA) that developed a bisphosphonate-related
      osteonecrosis that affect the jaws (BRONJ), including demographic aspects, as
      well as clinical and therapeutic issues. A search of PUBMED/MEDLINE, Scopus, and
      Cochrane databases from January 2003 to September 2011 was conducted with the
      objective of identifying publications that contained case reports regarding oral
      BRONJ in RA patients. Patients with RA who develop oral BRONJ are usually women
      above 60 years taking steroids and long-term alendronate. Most of them have
      osteoporosis, and lesions, triggered by dental procedures, are usually detected
      at stage II in the mandible. Although there is no accepted treatment protocol,
      these patients seem to have better outcomes with conservative approaches that
      include antibiotic therapy, chlorhexidine, and drug discontinuation.

PMID- 22376983
TI  - [Rheumatoid arthritis and meningeal nodules].
AB  - INTRODUCTION: Rheumatoid nodules are possible extra-articular manifestations of
      rheumatoid arthritis. These lesions are mainly located in subcutaneous tissues
      but may also rarely affect deep organs, exceptionally the meninges. CASE REPORT:
      We report herein a case of meningeal nodules observed in a 52-year-old man with
      rheumatoid arthritis who underwent brain MRI to explore an acute visual
      impairment. Subsequent MRIs showed similar new lesions contrasting with total
      regression of the initially observed lesions. The final control brain MRI
      performed four years after the onset of the ocular symptoms disclosed total
      involution of all the extra-axial nodular lesions, a course highly suggestive of
      meningeal rheumatoid nodules. CONCLUSION: During the follow-up period of this
      case, the patient was treated with methotrexate at doses too low to cross the
      blood brain barrier. Consequently, it is most likely that the meningeal lesions
      developed during the natural course of the disease. Despite the non-specific
      features of the first imaging findings, the radiological changes observed over
      time were consistent with the final diagnosis of rheumatoid nodules.

PMID- 22376987
TI  - Associations of home food availability, dietary intake, screen time and physical
      activity with BMI in young American-Indian children.
AB  - OBJECTIVE: To evaluate associations between home environmental factors and BMI of
      young American-Indian children. DESIGN: Cross-sectional and prospective study.
      SETTING: School-based obesity prevention trial (Bright Start) on a Northern
      Plains Indian reservation in South Dakota. Mixed model multivariable analysis was
      used to examine associations between child BMI categories (normal, overweight and
      obese) and home food availability, children's dietary intake and physical
      activity. Analyses were adjusted for age, gender, socio-economic status, parent
      BMI and school; prospective analyses also adjusted for study condition and
      baseline predictor and outcome variables. SUBJECTS: Kindergarten children (n =
      424, 51 % male; mean age = 5.8 years, 30 % overweight/obese) and
      parents/caregivers (89 % female; 86 % overweight/obese) had their height and
      weight measured and parents/caregivers completed surveys on home environmental
      factors (baseline and 2 years later). RESULTS: Higher fast-food intake and parent
      perceived barriers to physical activity were marginally associated with higher
      probabilities of a child being overweight and obese. Vegetable availability was
      marginally associated with lower probabilities of being overweight and obese. The
      associations between home environmental factors and child weight status at follow
      up were not significant. CONCLUSIONS: Findings indicate that selected aspects of
      the home environment are associated with weight status of American-Indian
      children. Obesity interventions with this population should consider helping
      parents to engage and model healthful behaviours and to increase availability of
      healthful foods at home.

PMID- 22376988
TI  - Does the world need a scientific society for research on how to improve
      healthcare?
AB  - In this editorial, we reflect on the arguments for starting a scientific society
      focused on research on how to improve healthcare. This society would take an
      inclusive approach to what constitutes healthcare. For instance, it should
      include mental health healthcare, treatment for substance abuse, the work of
      allied health professions, and preventive healthcare. The society would be open
      to researchers from all traditions. Thus, we take an inclusive approach to what
      constitutes scientific research, as long as it uses rigorous methods, is focused
      on improving healthcare, and aims at knowledge that can be transferred across
      settings. The society would primarily target scientific researchers but would
      invite others with an interest in this area of research, regardless of their
      discipline, position, field of application, or group affiliation (e.g.,
      improvement science, behavioral medicine, knowledge translation). A society would
      need fruitful collaboration with related societies and organizations, which may
      include having combined meetings. Special links may be developed with one or more
      journals. A website to provide information on relevant resources, events, and
      training opportunities is another key activity. It would also provide a voice for
      the field at funding agencies, political arenas, and similar institutions. An
      organizational structure and financial resources are required to develop and run
      these activities. Our aim is to start an international debate, to discover if we
      can establish a shared vision across academics and stakeholders engaged with
      creating scientific knowledge on how to improve healthcare. We invite readers to
      express their views in the online questionnaire accessed by following the URL
      link provided at the end of the editorial.

PMID- 22376989
TI  - Prevalence of nontuberculous mycobacteria infection, China, 2004-2009.

PMID- 22376990
TI  - Re: The radiology report - are we getting the message across?

PMID- 22376991
TI  - Novel orthobunyavirus in Cattle, Europe, 2011.
AB  - In 2011, an unidentified disease in cattle was reported in Germany and the
      Netherlands. Clinical signs included fever, decreased milk production, and
      diarrhea. Metagenomic analysis identified a novel orthobunyavirus, which
      subsequently was isolated from blood of affected animals. Surveillance was
      initiated to test malformed newborn animals in the affected region.

PMID- 22376996
TI  - A fatal presentation of dermatomyositis with facial swelling.
AB  - Juvenile dermatomyositis (JDM) is the most common inflammatory autoimmune
      myopathy in children. Most common presentations consist of heliotrophic rash
      and/or gottron's papules in addition to proximal muscle weakness. A typical
      presentations have been reported. We present a 13-year-old African American male
      who presented with a two-week history of bilateral periorbital edema that was
      unresponsive to glucocorticoids. He had elevated transaminases but no detectable
      muscle weakness. A muscle biopsy was consistent with juvenile dermatomyositis.
      This case highlights the need to consider dermatomyositis in cases of facial
      swelling and the use of aggressive immunosuppressive therapies due to its
      associated vasculopathies.

PMID- 22376997
TI  - Congenital cysts of the infant larynx.
AB  - OBJECTIVES: Congenital laryngeal cysts are a rare cause of neonatal airway
      obstruction. Two varieties can be distinguished, ductal cysts and saccular cysts.
      Treatment remains controversial, particularly with regard to saccular cysts, with
      some believing that endoscopic procedures leave cysts more prone to recurrence.
      We reviewed our management of congenital laryngeal cysts to determine the most
      effective intervention. METHODS: A review of all children treated by our unit for
      congenital laryngeal cysts between 2001 and 2011. Demographic data, age at and
      mode of presentation were noted. Operation notes were reviewed to determine the
      nature of each laryngeal cyst and treatment methodology. RESULTS: Ten children
      were identified, six with a ductal cyst of the vallecula and four with a saccular
      cyst, giving an overall incidence of 3.49 cases per 100,000 live births. Children
      of Pakistani ancestry were disproportionately represented, accounting for 40% of
      cases. Saccular cysts presented earlier with symptoms of more severe airway
      compromise, whilst vallecular cysts tended to present later with feeding
      difficulties and failure to thrive. Two-thirds of children with vallecular cysts
      had co-existing laryngomalacia. Treatment by single-stage endoscopic
      marsupialisation was effective in all cases at a mean follow-up of thirteen
      months. CONCLUSIONS: Congenital laryngeal cysts are rare, although they appear to
      be more common in the British-Pakistani population. Presentation depends on cyst
      size and proximity to the glottis and can be associated with laryngomalacia.
      Endoscopic marsupialisation is an effective means of treatment for ductal cysts
      and saccular cysts confined to the larynx.

PMID- 22377002
TI  - Evaluation of the IMMULITE(r) 2000 CMV IgM assay.
AB  - BACKGROUND: Diagnosis of cytomegalovirus (CMV) infection is challenging because
      of the high rate of asymptomatic infection and the low specificity of associated
      symptoms and signs. As a result, laboratory testing is an essential aid in making
      an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV
      infection. In pregnancy, diagnosis of primary infection is important because
      primary maternal infection increases fetal infection risk substantially. Fetal
      infection can result in serious sequelae ranging from neurological deficits to
      death. Diagnosis among the immunocompromised is also critical for the timely
      initiation of therapy that can reduce morbidity and mortality risk. METHODS: The
      IMMULITE(r) 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human
      serum or plasma to aid in the diagnosis of current or recent CMV infection. To
      determine expected values in apparently healthy subjects, 136 samples were
      tested. Reproducibility, normal range, and method comparison studies were also
      performed to evaluate the assay's performance. The assay's reproducibility was
      evaluated across three sites. Seven hundred and eighteen (n = 718) individual
      patient serum samples, which included samples from CMV IgM-positive (n = 109,
      determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n =
      210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients
      (n = 17) and from patients with potentially cross-reacting conditions (n = 136)
      were evaluated in the method comparison study. The positive, negative, and
      overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM
      assay (predicate assay) were determined. RESULTS: The assay demonstrated
      excellent reproducibility with a total CV of less than 10%. The positive,
      negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS
      assay were > 95% for the method comparison samples. Among potentially cross
      reactive samples, the overall agreement between the two assays was 96%.
      Similarly, among the immunocompromised and pregnant subjects, the overall
      agreement was ~96% and ~97%, respectively. CONCLUSIONS: The IMMULITE 2000 CMV IgM
      assay demonstrated excellent reproducibility, minimal cross-reactivity, and
      performance comparable to that of the VIDAS CMV IgM assay. It can aid in the
      diagnosis of acute CMV or recent CMV infection by qualitatively detecting the CMV
      IgM antibodies in human serum or plasma.

PMID- 22376998
TI  - Food foreign body injuries.
AB  - RATIONALE AND AIM: The purpose of this study is to acquire a better understanding
      of Food Foreign Bodies (FFB) injuries in children characterizing the risk of
      complications and prolonged hospitalization due to food items according to
      patients' characteristics, circumstances of the accident, Foreign Body (FB)
      features and FB location, as emerging from the SUSY Safe Web-Registry. METHODS:
      The present study uses data provided by the SUSY Safe Project, a DG SANCO co
      funded project started in February 2005, which was aimed at establishing an
      international registry of cases of Foreign Bodies (FB) injuries in children aged
      0-14 years. The analysis was carried out on injuries due to a food item. FB
      location was reported according to ICD9-CM code: ears (ICD931), nose (ICD932),
      pharynx and larynx (ICD933) trachea, bronchi and lungs (ICD934), mouth, esophagus
      and stomach (ICD935). Age and gender injury distributions were assessed. Data
      regarding adult supervision and activity before injury were also evaluated. FBs
      which most frequently cause complications were identified. The association
      between children age, adult presence, object characteristics and
      hospitalization/complications was computed using unweighted odds ratios and the
      related 95% confidence intervals. RESULTS: 16,878 FB injuries occurred in
      children aged 0-14 years have been recorded in the SUSY Safe databases. FB type
      was specified in 10,564 cases; among them 2744 (26%) were due to a food item. FB
      site was recorded in 1344 cases: FB was located in the ears in 99 patients, while
      1140 occurred in the upper and lower respiratory tract; finally, 105 food items
      were removed from mouth, esophagus and stomach. Complications occurred in 176
      cases and the most documented was pulmonary or bronchial infections (23%)
      followed emphysema or atelectasis and by and asthma (7%). Bones were the
      commonest retrieved FFB encountered in this study, while nuts seem to be the FFB
      most frequently associated to complications. CONCLUSIONS: On the basis of this
      study we make the strong recommendation that parents should be adequately
      educated and provide age-appropriate food to their children and be present in
      order to supervise them during eating especially during a critical period ranging
      from 2 to 3 years of age.

PMID- 22377004
TI  - A novel root analogue dental implant using CT scan and CAD/CAM: selective laser
      melting technology.
AB  - Direct laser metal forming (DLMF) is a new technique which allows solids with
      complex geometry to be produced by annealing metal powder microparticles in a
      focused laser beam, according to a computer-generated three-dimensional (3D)
      model. For dental implants, the fabrication process involves the laser-induced
      fusion of titanium microparticles, in order to build, layer by layer, the desired
      object. Modern computed tomography (CT) acquisition and 3D image conversion,
      combined with the DLMF process, allows the fabrication of custom-made, root
      analogue implants (RAI), perfect copies of the radicular units that need
      replacing. This report demonstrates the successful clinical use of a custom-made,
      root-analogue DLMF implant. CT images of the residual non-restorable root of a
      right maxillary premolar were acquired and modified with specific software into a
      3D model. From this model, a custom-made, root-analogue, DLMF implant was
      fabricated. Immediately after tooth extraction, the root-analogue implant was
      placed in the extraction socket and restored with a single crown. At the 1-year
      follow-up examination, the custom-made implant showed almost perfect functional
      and aesthetic integration. The possibility of fabricating custom-made, root
      analogue DLMF implants opens new interesting perspectives for immediate placement
      of dental implants.

PMID- 22377010
TI  - Latissimus dorsi (LD) free flap and reconstruction plate used for extensive
      maxillo-mandibular reconstruction after tumour ablation.
AB  - PURPOSE: The purpose of this study was to consider the indications and evaluate
      the clinical advantages and disadvantages including, results and complications,
      of immediate reconstruction using a latissimus dorsi (LD) free flap and
      reconstruction plate (R-plate) in advanced oro-mandibular tumour resection.
      METHODS AND MATERIALS: Our cohort included 116 patients who underwent LD free
      flap and R-plate reconstruction. Flap survival, postoperative function,
      donor/recipient site complication and aesthetics were evaluated. RESULTS: Our
      series demonstrated a 99.1% flap survival rate. One case required a contralateral
      LD free flap reconstruction after the initial flap failed due to pedicle kinking.
      Twelve patients needed the plate to be removed and replaced (n=4, plate fracture;
      n=2, plate exposure) or definite reconstruction with free fibular flap and
      implant installation. Donor site complications included seroma accumulation,
      scarring, and discomfort of the shoulder girdle. The size of the skin paddle
      ranged from 6 * 10 cm to 12 * 18 cm (12 were double paddled).The facial contour
      was acceptable without sagging of the flap. The flap was tolerant to irradiation
      and was resistant to the exposure of the plate at the symphyseal arch.
      CONCLUSION: Our series of primary reconstruction with LD free flaps and R-plates
      showed the retention of mandibular function and the reconstruction of
      considerably large soft tissue can be achieved successfully. This reconstruction
      scheme can be indicated for large-volume defects in the oro-mandibular area when
      the area cannot be covered by a single osteocutaneous free flap, has undergone
      extensive oncologic resection for advanced or high recurrence rate malignancy and
      when immediate postoperative chemotherapy and/or irradiation is necessary.

PMID- 22377013
TI  - Travelers as sentinels for chikungunya fever, Brazil.

PMID- 22377014
TI  - Understanding the concept of a "good death" among bereaved family caregivers of
      cancer patients in Singapore.
AB  - OBJECTIVE: The aim of this study was to examine the concept of a good death from
      the perspectives of both the dying person and the family caregiver, as perceived
      by bereaved family caregivers of advanced cancer patients. METHOD: The data were
      gathered from five focus group discussions and one face-to-face qualitative
      interview conducted over 8 months among 18 bereaved family caregivers recruited
      from a local hospice. The transcripts of the focus groups and the interview were
      entered into NVivo Version 8 and were analyzed using the thematic approach.
      RESULTS: A good death may be understood as having the biopsychosocial and
      spiritual aspects of life handled well at the end of life. Five major themes were
      identified. These were preparation for death, family and social relationships,
      moments at or near death, comfort and physical care, and spiritual well-being.
      Differences were also noted in what is important at the end of life between the
      patients and caregivers. Having a quick death with little suffering was perceived
      to be good by the patient, but the family caregiver wanted to be able to say a
      final goodbye to the patient. Patients tend to prefer not to die in their
      children's presence but the children wished to be present for the final moment.
      In addition, family caregivers reported it was important for them to be able to
      give the patients permission to die, to feel recognized for the efforts made, and
      to have had a fulfilling caregiving experience. SIGNIFICANCE OF RESULTS: Whereas
      there are global attributes of a good death, our findings suggest that patients
      and family caregivers may define a good death differently. Therefore, there is a
      need to respect, address, and reconcile the differences, so that all parties may
      have a good experience at the end of a person's life.

PMID- 22377015
TI  - Cortactin and focal adhesion kinase as predictors of cancer risk in patients with
      premalignant oral epithelial lesions.
AB  - There is a need for novel and accurate biomarkers based on genetic abnormalities
      capable of predicting the risk of malignant transformation of epithelial lesions
      of the oral cavity. Therefore, we investigate the role of cortactin and focal
      adhesion kinase (FAK) protein expression in oral dysplasias and their potential
      utility as cancer risk markers. Cortactin and FAK expression were
      immunohistochemically evaluated in 64 patients with oral epithelial dysplasia.
      During follow-up, 17 of 64 patients developed an oral squamous cell carcinoma
      (OSCC). Increased immunoexpression of cortactin and FAK was found in 52 and 27 of
      64 oral dysplasias, respectively, and the expression of both proteins increased
      with the grade of dysplasia. Increased cortactin and FAK expression was also
      observed in 13 and 15 OSCC, respectively. Overall, cortactin and FAK expression
      was maintained or further augmented in the oral squamous cell carcinoma compared
      to the patient-matched preinvasive lesion. Univariate analysis showed that
      cortactin and FAK expression, as well as histological grading were significantly
      associated with oral cancer risk. Strong coexpression of both proteins reflected
      a significantly higher cancer risk than that of weak to moderate expression or
      than whenever only one of those proteins showed a strong expression. In
      multivariate analysis, premalignant oral lesions which exhibited a high
      coexpression of cortactin and FAK showed a significant risk of developing an OSCC
      (HR=6.298). Our results indicate that strong immunoexpression of cortactin and
      FAK, and not only one of them, is a predicting factor for increased cancer risk
      in oral premalignant lesions.

PMID- 22377016
TI  - Escherichia coli O104:H4 infections and international travel.
AB  - We analyzed travel-associated clinical isolates of Escherichia coli O104:H4,
      including 1 from the 2011 German outbreak and 1 from a patient who returned from
      the Philippines in 2010, by genome sequencing and optical mapping. Despite
      extensive genomic similarity between these strains, key differences included the
      distribution of toxin and antimicrobial drug-resistance determinants.

PMID- 22377027
TI  - Seven naphtho-gamma-pyrones from the marine-derived fungus Alternaria alternata:
      structure elucidation and biological properties.
AB  - Eight bioactive pyrone derivatives were identified from the culture of
      Alternaria alternata strain D2006, isolated from the marine soft coral
      Denderonephthya hemprichi, which was selected as its profound antimicrobial
      activities. The compounds were assigned as pyrophen (1), rubrofusarin B (2),
      fonsecin (3), and fonsecin B (5) beside to the four dimeric naphtho-gamma
      pyrones; aurasperone A (6), aurasperone B (7), aurasperone C (8), and aurasperone
      F (9). Structures of the isolated compounds were identified on the basis of 1D
      and 2D NMR spectroscopy and mass (EI, ESI, HRESI) data, and by comparison with
      the literature. Configuration of the four dimeric naphtho-gamma-pyrones 6-9 was
      analyzed by CD spectra, exhibiting an identical stereochemistry.

PMID- 22377032
TI  - Enhanced surveillance for white-nose syndrome in bats.

PMID- 22377033
TI  - Microglia and neuronal cell death.
AB  - Microglia, the brain's innate immune cell type, are cells of mesodermal origin
      that populate the central nervous system (CNS) during development.
      Undifferentiated microglia, also called ameboid microglia, have the ability to
      proliferate, phagocytose apoptotic cells and migrate long distances toward their
      final destinations throughout all CNS regions, where they acquire a mature
      ramified morphological phenotype. Recent studies indicate that ameboid microglial
      cells not only have a scavenger role during development but can also promote the
      death of some neuronal populations. In the mature CNS, adult microglia have
      highly motile processes to scan their territorial domains, and they display a
      panoply of effects on neurons that range from sustaining their survival and
      differentiation contributing to their elimination. Hence, the fine tuning of
      these effects results in protection of the nervous tissue, whereas perturbations
      in the microglial response, such as the exacerbation of microglial activation or
      lack of microglial response, generate adverse situations for the organization and
      function of the CNS. This review discusses some aspects of the relationship
      between microglial cells and neuronal death/survival both during normal
      development and during the response to injury in adulthood.

PMID- 22377034
TI  - Laboratory practices and incidence of non-O157 shiga toxin-producing Escherichia
      coli infections.
AB  - We surveyed laboratories in Washington State, USA, and found that increased use
      of Shiga toxin assays correlated with increased reported incidence of non-O157
      Shiga toxin-producing Escherichia coli (STEC) infections during 2005-2010.
      Despite increased assay use, only half of processed stool specimens underwent
      Shiga toxin testing during 2010, suggesting substantial underdetection of  non
      O157 STEC infections.

PMID- 22377043
TI  - Development of marker-free transgenic Jatropha plants with increased levels of
      seed oleic acid.
AB  - BACKGROUND: Jatropha curcas is recognized as a new energy crop due to the
      presence of the high amount of oil in its seeds that can be converted into
      biodiesel. The quality and performance of the biodiesel depends on the chemical
      composition of the fatty acids present in the oil. The fatty acids profile of the
      oil has a direct impact on ignition quality, heat of combustion and oxidative
      stability. An ideal biodiesel composition should have more monounsaturated fatty
      acids and less polyunsaturated acids. Jatropha seed oil contains 30% to 50%
      polyunsaturated fatty acids (mainly linoleic acid) which negatively impacts the
      oxidative stability and causes high rate of nitrogen oxides emission. RESULTS:
      The enzyme 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine delta 12-desaturase (FAD2)
      is the key enzyme responsible for the production of linoleic acid in plants. We
      identified three putative delta 12 fatty acid desaturase genes in Jatropha
      (JcFAD2s) through genome-wide analysis and downregulated the expression of one of
      these genes, JcFAD2-1, in a seed-specific manner by RNA interference technology.
      The resulting JcFAD2-1 RNA interference transgenic plants showed a dramatic
      increase of oleic acid (> 78%) and a corresponding reduction in polyunsaturated
      fatty acids (< 3%) in its seed oil. The control Jatropha had around 37% oleic
      acid and 41% polyunsaturated fatty acids. This indicates that FAD2-1 is the major
      enzyme responsible for converting oleic acid to linoleic acid in Jatropha. Due to
      the changes in the fatty acids profile, the oil of the JcFAD2-1 RNA interference
      seed was estimated to yield a cetane number as high as 60.2, which is similar to
      the required cetane number for conventional premium diesel fuels (60) in Europe.
      The presence of high seed oleic acid did not have a negative impact on other
      Jatropha agronomic traits based on our preliminary data of the original plants
      under greenhouse conditions. Further, we developed a marker-free system to
      generate the transgenic Jatropha that will help reduce public concerns for
      environmental issues surrounding genetically modified plants. CONCLUSION: In this
      study we produced seed-specific JcFAD2-1 RNA interference transgenic Jatropha
      without a selectable marker. We successfully increased the proportion of oleic
      acid versus linoleic in Jatropha through genetic engineering, enhancing the
      quality of its oil.

PMID- 22377049
TI  - NDM-1-producing Klebsiella pneumoniae, Croatia.

PMID- 22377050
TI  - Involvement of calcitonin gene-related peptide and CCL2 production in CD40
      mediated behavioral hypersensitivity in a model of neuropathic pain.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro
      nociceptive role after peripheral nerve injury upon its release from primary
      afferent neurons in preclinical models of neuropathic pain. We previously
      demonstrated a critical role for spinal cord microglial CD40 in the development
      of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity.
      Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral
      hypersensitivity. First, L5Tx was found to significantly induce CGRP expression
      in wild-type (WT) mice up to 14 days post-L5Tx. This increase in CGRP expression
      was reduced in CD40 knockout (KO) mice at day 14 post-L5Tx. Intrathecal injection
      of the CGRP antagonist CGRP8-37 significantly blocked L5Tx-induced mechanical
      hypersensitivity. In vitro, CGRP induced glial IL-6 and CCL2 production, and CD40
      stimulation added to the effects of CGRP in neonatal glia. Further, there was
      decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx.
      However, CGRP8-37 did not significantly affect spinal cord CCL2 production
      following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes
      to the maintenance of behavioral hypersensitivity following peripheral nerve
      injury in part through two distinct pathways, the enhancement of CGRP expression
      and spinal cord CCL2 production.

PMID- 22377052
TI  - Highly pathogenic avian influenza (H5N1) outbreaks in wild birds and poultry,
      South Korea.
AB  - Highly pathogenic avian influenza (H5N1) among wild birds emerged simultaneously
      with outbreaks in domestic poultry in South Korea during November 2010-May 2011.
      Phylogenetic analysis showed that these viruses belonged to clade 2.3.2, as did
      viruses found in Mongolia, the People's Republic of China, and Russia in 2009 and
      2010.

PMID- 22377063
TI  - Adherence to oseltamivir guidelines during influenza pandemic, the Netherlands.

PMID- 22377068
TI  - Bioethics and the conditions for human agency.

PMID- 22377069
TI  - Responsibilities for healthcare -- Kantian reflections.

PMID- 22377061
TI  - Selection of reference genes in different myocardial regions of an in vivo
      ischemia/reperfusion rat model for normalization of antioxidant gene expression.
AB  - BACKGROUND: Changes in cardiac gene expression due to myocardial injury are
      usually assessed in whole heart tissue. However, as the heart is a heterogeneous
      system, spatial and temporal heterogeneity is expected in gene expression.
      RESULTS: In an ischemia/reperfusion (I/R) rat model we evaluated gene expression
      of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod) and
      thioredoxin reductase (trxr1) upon short (4 h) and long (72 h) reperfusion times
      in the right ventricle (RV), and in the ischemic/reperfused (IRR) and the remote
      region (RR) of the left ventricle. Gene expression was assessed by Real-time
      reverse-transcription quantitative PCR (RT-qPCR). In order to select most stable
      reference genes suitable for normalization purposes, in each myocardial region we
      tested nine putative reference genes by geNorm analysis. The genes investigated
      were: Actin beta (actb), Glyceraldehyde-3-P-dehydrogenase (gapdh), Ribosomal
      protein L13A (rpl13a), Tyrosine 3-monooxygenase (ywhaz), Beta-glucuronidase
      (gusb), Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt), TATA binding box
      protein (tbp), Hydroxymethylbilane synthase (hmbs), Polyadenylate-binding protein
      1 (papbn1). According to our findings, most stable reference genes in the RV and
      RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes
      were recommended for normalization purposes; however, in view of experimental
      feasibility limitations, target gene expression could be normalized against the
      three most stable reference genes (ywhaz/pabp/hmbs) without loss of sensitivity.
      In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the
      former in all myocardial regions and the latter in IRR alone. trxr1 expression
      did not vary. CONCLUSIONS: This study provides a validation of reference genes in
      the RV and in the anterior and posterior wall of the LV of cardiac
      ischemia/reperfusion model and shows that gene expression should be assessed
      separately in each region.

PMID- 22377070
TI  - The concept of autonomy and its role in Kantian ethics.

PMID- 22377071
TI  - Don't lie! . . . Why not? - how to argue for truthfulness in medical practice.

PMID- 22377072
TI  - What is the Habermasian perspective in bioethics?

PMID- 22377073
TI  - Habermas, human agency, and human genetic enhancement -- the grown, the made, and
      responsibility for actions.

PMID- 22377074
TI  - Protecting humanity -- Habermas and his critics on the ethics of emerging
      biotechnologies.

PMID- 22377075
TI  - On moral enhancement from a Habermasian perspective.

PMID- 22377076
TI  - Bioethics as science fiction -- making sense of Habermas's The Future of Human
      Nature.

PMID- 22377077
TI  - Professionalism department.

PMID- 22377078
TI  - When doctors break the rules -- on the ethics of physician noncompliance.

PMID- 22377079
TI  - Medical humanities, ethics, and disability -- one fellow's confession and
      transformation.

PMID- 22377080
TI  - Disgust in bioethics.

PMID- 22377081
TI  - The case -- IVF treatment for an HIV-discordant transgender couple?.

PMID- 22377086
TI  - Culturing stool specimens for Campylobacter spp., Pennsylvania, USA.
AB  - In 2010, we surveyed 176 clinical laboratories in Pennsylvania regarding stool
      specimen testing practices for enteropathogens, including Campylobacter spp. Most
      (96.3%) routinely test for Campylobacter spp. In 17 (15.7%), a stool antigen test
      is the sole method for diagnosis. We recommend that laboratory practice
      guidelines for Campylobacter spp. testing be developed.

PMID- 22377089
TI  - Investigating the drinking patterns of young people over the course of the
      evening at weekends.
AB  - BACKGROUND: Memory deficits lead to distortion when long recall periods are used
      to assess alcohol consumption. We used the recently developed Internet-based cell
      phone-optimised assessment technique (ICAT) to describe the drinking patterns of
      young people over the course of Thursday, Friday and Saturday evenings and to
      compare the amounts reported during the drinking sessions in question with those
      in the retrospective baseline assessment. METHODS: Using hyperlinks in text
      messages sent to their cell phones over five weeks, 183 young adults in French
      speaking Switzerland completed a total of 8646 questionnaires at 8 pm, 9 pm, 10
      pm, 11 pm, midnight and 11 am the next morning over 1441 evenings. FINDINGS:
      Participants consumed an average of three drinks on Thursday evenings, four on
      Friday evenings and five and a half on Saturday evenings. The multi-group and
      multi-level latent growth curves showed that while the difference was minimal at
      the beginning of the evening, consumption decreased over the course of the
      evening on Thursdays, remained about stable on Fridays and increased on Saturdays
      between both genders. The amounts indicated in the evening assessments were up to
      twice as high as those indicated retrospectively. CONCLUSIONS: Using
      participants' cell phones, ICAT appears to be a convenient method for collecting
      alcohol-related data throughout the evening. Due to the significant impact of
      evening drinking patterns on the total amount consumed and related consequences,
      it is important to prevent the average increase of drinking that is likely to
      occur on Saturday evenings among young people.

PMID- 22377091
TI  - The effects of rearing condition on methamphetamine self-administration and cue
      induced drug seeking.
AB  - BACKGROUND: Little is known about the effect of different rearing conditions on
      the effects of methamphetamine and whether the introduction of enriched rearing
      conditions at different stages of development could produce different behavioral
      outcomes. METHODS: In Experiment 1, rats were reared in either enriched (EE) or
      isolated environments (IE) from PND 21 to 60. In Experiment 2, two groups of
      animals were handled in the same fashion as those in Experiment 1. Additional two
      groups were housed in IE during the first 20 or 30 days and then housed under EE
      for the remaining 20 or 10 days respectively. Locomotor activity and Morris Water
      Maze were tested. The effects of rearing conditions on methamphetamine (METH)
      self-administration were investigated. RESULTS: IE animals exhibited higher
      levels of locomotion than EE animals, but EE animals showed enhanced Morris water
      maze performance. Animals reared in IE for 30 and 40 days more readily acquired
      METH self-administration, compared to those reared in IE for 20 and in EE for 40
      days respectively. However, the effect of rearing conditions was only seen at the
      lowest dose tested under FR schedule and breakpoints obtained from PR schedule
      were not significantly affected. Those reared in IE for 20 and EE for 40 days
      animals produced significantly fewer responses during the extinction and cue
      induced reinstatement of METH self-administration, compared with animals reared
      in IE for 30 and 40 days, respectively. CONCLUSION: Rearing condition plays a
      significant role in locomotor activity, spatial memory and behavioral effects of
      METH.

PMID- 22377090
TI  - Intravenous gestational nicotine exposure results in increased motivation for
      sucrose reward in adult rat offspring.
AB  - BACKGROUND: Prenatal tobacco smoke exposure is associated with alterations in
      motivated behavior in offspring, such as increased consumption of highly
      palatable foods and abused drugs. Animal models show that gestational nicotine
      (GN) exposure mediates changes in responding for sucrose and drug reward.
      METHODS: A novel, intermittent low-dose intravenous (IV) exposure model was used
      to administer nicotine (0.05 mg/kg/injection) or saline 3*/day to rats on
      gestational days 8-21. Two experiments investigated the effect of IV GN on (1)
      the habituation of spontaneous locomotor activity and on (2) sucrose reinforced
      responding in offspring. For the operant experiments, animals acquired fixed
      ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying
      concentrations (0, 3, 10, 30, and 56%; Latin-square) according to a FR-3, and
      then a progressive-ratio (PR) schedule. Male and female adult offspring were
      used. RESULTS: IV GN did not alter birth or growth weight, or the number of pups
      born. No between-group differences in habituation to spontaneous locomotor
      activity were observed. FR testing produced an inverted U-shaped response curve,
      and rats showed peak responding for 10% sucrose reinforcement. Neither gestation
      nor sex affected responding, suggesting equivalent sensitivity to varying sucrose
      concentrations. PR testing revealed that GN rats showed greater motivation for
      sucrose reinforcement relative to controls. CONCLUSIONS: A low-dose, IV GN
      exposure model resulted in increased motivation to respond for sucrose
      reinforcement in adult offspring. This suggests that using a low number of
      cigarettes throughout pregnancy will result in increased motivation for highly
      palatable foods in adult, and perhaps, adolescent offspring.

PMID- 22377092
TI  - ANAPC1 and SLCO3A1 are associated with nicotine dependence: meta-analysis of
      genome-wide association studies.
AB  - Twin and family studies have shown that there is substantial evidence for a
      genetic component in the vulnerability to nicotine dependence (ND). The purpose
      of this study was to perform a meta-analysis on two genome-wide association (GWA)
      data involving 1079 cases of ND and 1341 controls in Caucasian populations.
      Through meta-analysis we identified 50 SNPs associated with ND with p<10(-4). The
      best associated SNP rs7163369 (p=3.27*10(-6)) was located at 15q26 within SLCO3A1
      gene while the second best SNP was rs9308631 (p=9.06*10(-6)) at 2q12.1 near
      ANAPC1. The third interesting locus rs688011 (p=1.08*10(-5)) was at 11q23.2
      intergenic between NCAM1 and TCC12. Through meta-analysis, we found two
      additional ND associated genes ZCCHC14 (the top SNP was rs13334632, p=1.28*10(
      5)) and KANK1 (the top SNP was rs13286166, p=1.49*10(-5)). The first top SNP
      rs7163369 within SLCO3A1 in the meta-analysis was replicated in the Australian
      twin-family study of 778 families (p=6.11*10(-5)) while SNP rs9653414 within
      ANAPC1 (p=4.61*10(-5)) in the meta-analysis was replicated in the family sample
      (p=9.31*10(-4)). Furthermore, rs2241617 in ZCCHC14 and rs4742225 in KANK1 showed
      strong associations with ND (p=1.06*10(-7) and 4.81*10(-7), respectively) in the
      replication sample. In addition, several SNPs of these loci (ANAPC1, KANK1,
      NACM1, TCC12, SLCO3A1 and ZCCHC14) were associated with alcohol dependence. In
      conclusion, we identified several loci associated with ND through meta-analysis
      of two GWA studies. These findings offer the potential for new insights into the
      pathogenesis of ND.

PMID- 22377093
TI  - Towards an understanding of the information dynamics of the handover process in
      aged care settings--a prerequisite for the safe and effective use of ICT.
AB  - BACKGROUND: Poor clinical handover has been associated with inaccurate clinical
      assessment and diagnosis, delays in diagnosis and test ordering, medication
      errors and decreased patient satisfaction in the acute care setting. Research on
      the handover process in the residential aged care sector is very limited.
      PURPOSE: The aims of this study were to: (i) Develop an in-depth understanding of
      the handover process in aged care by mapping all the key activities and their
      information dynamics, (ii) Identify gaps in information exchange in the handover
      process and analyze implications for resident safety, (iii) Develop practical
      recommendations on how information communication technology (ICT) can improve the
      process and resident safety. METHODS: The study was undertaken at a large
      metropolitan facility in NSW with more than 300 residents and a staff including
      55 registered nurses (RNs) and 146 assistants in nursing (AINs). A total of 3
      focus groups, 12 interviews and 3 observation sessions were conducted over a
      period from July to October 2010. Process mapping was undertaken by translating
      the qualitative data via a five-category code book that was developed prior to
      the analysis. RESULTS: Three major sub-processes were identified and mapped. The
      three major stages are Handover process (HOP) I "Information gathering by RN",
      HOP II "Preparation of preliminary handover sheet" and HOP III "Execution of
      handover meeting". Inefficient processes were identified in relation to the
      handover including duplication of information, utilization of multiple
      communication modes and information sources, and lack of standardization.
      CONCLUSION: By providing a robust process model of handover this study has made
      two critical contributions to research in aged care: (i) a means to identify
      important, possibly suboptimal practices; and (ii) valuable evidence to plan and
      improve ICT implementation in residential aged care. The mapping of this process
      enabled analysis of gaps in information flow and potential impacts on resident
      safety. In addition it offers the basis for further studies into a process that,
      despite its importance for securing resident safety and continuity of care, lacks
      research.

PMID- 22377094
TI  - Organizational framework for health information technology.
AB  - PURPOSE: We do not yet know how best to design, implement, and use health
      information technology (IT). A comprehensive framework that captures knowledge on
      the implementation, use, and optimization of health IT will help guide more
      effective approaches in the future. METHODS: The authors conducted a targeted
      review of existing literature on health IT implementation and use, including
      health IT-related theories and models. By crosswalking elements of current
      theories and models, the authors identified five major facets of an
      organizational framework that provides a structure to organize and capture
      information on the implementation and use of health IT. RESULTS: The authors
      propose a novel organizational framework for health IT implementation and use
      with five major facets: technology, use, environment, outcomes, and temporality.
      Each major facet is described in detail along with associated categories and
      measures. CONCLUSION: The proposed framework is an essential first step toward
      ensuring a more consistent and comprehensive understanding of health IT
      implementation and use and a more rigorous approach to data collection,
      measurement development, and theory building.

PMID- 22377096
TI  - Elastic behavior of neodymium based manganites.
AB  - With a view to investigate the elastic behavior of Nd(0.67)A(0.33)MnO(3) (where
      A=Ca, Sr, Ba, Pb) manganite system, the samples were prepared by the sol gel
      method. After characterizing the samples structurally, a systematic investigation
      of ultrasonic longitudinal and transverse sound velocities of all the samples was
      undertaken by pulse transmission technique in the temperature range, 100-300K. It
      has been found that all the elasticity parameters, including Debye temperature,
      are found to increase continuously with increasing ionic radii of the dopant ion.
      All the samples are also found to exhibit anomalies in both the longitudinal and
      transverse velocities near their ferro to para magnetic transition (T(C))
      temperatures. Apart from this, Nd(0.67)Ca(0.33)MnO(3) sample is also found to
      exhibit, a transition at its charge ordering temperature (T(co)). An explanation
      for the observed elastic anomalies based on a mean field theory has been given.

PMID- 22377097
TI  - Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes.
AB  - Posterior reversible encephalopathy syndrome (PRES) can present with focal
      neurologic deficits, mimicking a stroke and can often represent a diagnostic
      challenge when presenting atypically. A high degree of suspicion is required in
      the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP)
      is utilized in many institutions as the first line in acute stroke imaging. CTP
      has proved to be a very sensitive measure of cerebral blood flow dynamics, most
      commonly employed to delineate the infarcted tissue from penumbra (at-risk
      tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such
      as seizures, hypoglycemia, tumors, migraines and PRES. In this article we
      describe a case of PRES in an elderly bone marrow transplant recipient who
      presented with focal neurological deficits concerning for a cerebrovascular
      accident. CTP played a pivotal role in the diagnosis and initiation of
      appropriate management. We also briefly discuss the pathophysiology of PRES.

PMID- 22377101
TI  - MTR abnormalities in subjects at ultra-high risk for schizophrenia and first
      episode schizophrenic patients compared to healthy controls.
AB  - BACKGROUND: Neuroimaging studies have suggested gray (GM) and white matter (WM)
      abnormalities in early stages of schizophrenia. We aimed at evaluating subtle
      parenchymal alterations in individuals at ultra-high risk (UHR) for transition
      into psychosis and first-episode schizophrenic (FES) patients by measuring the
      magnetization transfer ratio (MTR). METHODS AND MATERIAL: In a cross-sectional
      study magnetization transfer images and high-resolution volumetric T1-weighted
      images were acquired in 70 age- and gender-matched subjects (25 UHR subjects, 16
      FES patients and 29 controls) in a 1.5Tesla scanner. Following normalization of
      MTR-maps the intensity histograms were analyzed by performing a Kruskal-Wallis
      test. RESULTS: Gray matter MTR decreases were depicted in UHR subjects solely,
      involving the cingulate gyrus and precentral cortex. WM MTR alterations were more
      pronounced in FES than in UHR patients and exclusively affected the frontal lobe
      bilaterally. In addition, UHR subjects showed bilateral MTR decreases at the
      stria terminalis though statistically significant only on the left side
      (p=0.018.) CONCLUSION: Our results indicate GM affection earlier on during
      disease progression as well as cumulative WM affection within frontal lobes
      during transition from UHR to FES. MTR reductions at the stria terminalis of UHR
      patients points to the involvement of the extended amygdala in the prodromal
      disease stage.

PMID- 22377103
TI  - Pro12Ala polymorphism of the PPAR-gamma2 gene, metabolic syndrome and response to
      metformin in clozapine-treated patients.

PMID- 22377102
TI  - Cognitive changes following antidepressant or antipsychotic treatment in
      adolescents at clinical risk for psychosis.
AB  - BACKGROUND: Improving neurocognitive abilities is a treatment priority in
      schizophrenia, however, pharmacological efforts to enhance deficits after illness
      onset have resulted in quite modest results that are of questionable clinical
      meaningfulness. Individuals at clinical risk for psychosis demonstrate
      neurocognitive impairments intermediate to the level of deficits observed in
      schizophrenia and normative performance, suggesting that a similar magnitude of
      improvement might result in more clinically meaningful change. In this study, we
      examined neurocognitive changes after six months of treatment in adolescents with
      clinical signs of risk for psychosis. METHODS: Adolescents who were referred to
      the Recognition and Prevention program, which is focused on treatment and
      research for individuals at a clinical high risk for psychosis, were followed in
      a naturalistic treatment design. At study entry and approximately six months
      after starting treatment, we examined neuropsychological functioning and clinical
      symptoms for patients who remained off medications (OFF; N=27), started selective
      serotonin reuptake inhibitor antidepressant medication (AD; N=15), or started a
      second-generation antipsychotic medication (AP; N=11) within three months of
      study entry. We also included a locally recruited healthy comparison group (HC;
      N=17). RESULTS: The clinical groups were not significantly different on baseline
      demographic, neurocognitive, or clinical symptom measures. Linear mixed models
      were used to examine cognitive changes, with time between assessments, depressive
      symptom severity, and attenuated positive symptom severity as random effects.
      Group by time effects were observed in sustained attention and verbal learning,
      with the AD group showing a more favorable response than the AP group. The AD
      group's improvements were not significantly different from the HC or OFF group.
      CONCLUSION: Early intervention for those at clinical high risk for psychosis may
      result in neurocognitive improvements. These improvements were observed for those
      prescribed antidepressant, but not antipsychotic medications even though the
      groups did not differ in clinical symptom severity or treatment response.

PMID- 22377104
TI  - Self-esteem as a mediator of the relationship between role functioning and
      symptoms for individuals with severe mental illness: a prospective analysis of
      Modified Labeling theory.
AB  - BACKGROUND: Despite a growing body of evidence supporting the efficacy of
      psychosocial rehabilitation for individuals with severe mental illness (SMI), a
      large proportion of these individuals remain unable to maintain basic social
      roles such as employee, parent, or spouse. This study investigated whether
      changes in role functioning over time impact symptom severity indirectly through
      the mechanism of changes in self-esteem as posited by Modified Labeling theory.
      METHODS: The study sample was composed of 148 individuals diagnosed with
      schizophrenia, schizoaffective disorder, bipolar disorder with psychotic
      features, and major depression with psychotic features who elected to participate
      in community-based psychosocial rehabilitation services. Measures of role
      functioning, self-esteem, and psychiatric symptoms were gathered at baseline and
      six months through a combination of structured clinical interviews and self
      report surveys. RESULTS: SEM results at baseline provided support for a model in
      which self-esteem fully mediated the relationship between role functioning and
      psychiatric symptoms. The final model explained 20% of the variance in
      psychiatric symptoms. Analyses at six months post-baseline (time 2) indicate that
      changes in self-esteem fully mediated the relationship between changes in role
      functioning and changes in psychiatric symptoms. The final change model explained
      23% of the variance in changes in psychiatric symptoms. CONCLUSION: Results
      provide empirical support for the principles underlying Modified Labeling theory.
      Implications include the need for interventions that focus on social
      participation as a means of improving self-esteem, thereby decreasing symptom
      exacerbation and future relapse for people with SMI.

PMID- 22377105
TI  - Reduced arterial compliance in patients with psychiatric diagnoses.
AB  - BACKGROUND: Peripheral arterial compliance is a measure of elasticity of the
      arteries that has been found to be a robust predictor of prevalent
      arteriosclerosis as well as incident stroke and myocardial infarction.
      Psychiatric diagnoses and second generation antipsychotics may contribute to
      cardiovascular risk and stroke, but effects on peripheral arterial compliance are
      unknown. This study compared peripheral arterial compliance in healthy male
      controls to male patients with psychiatric diagnoses who were treated with
      quetiapine or risperidone or off antipsychotics at time of testing. METHODS: The
      groups consisted of 63 patients with mental illness taking quetiapine,
      risperidone, or no antipsychotics. There were 111 males in the control group.
      Mean thigh and calf arterial compliance among four groups were compared by
      ANCOVA, adjusting for body mass index and Framingham Risk Score. All patients
      were also compared to the control group. Compliance was measured with a
      computerized plethysmography device. RESULTS: Patients (n=63) had significantly
      lower arterial compliance in both thigh and calf than the controls. Arterial
      compliance in the calf was significantly lower in the subgroups of quetiapine
      (n=16) and risperidone (n=19) treated, and in unmedicated (n=28) patients than in
      controls. In the thigh, patients taking either quetiapine or risperidone had
      significantly lower arterial compliance than controls. These subgroups did not
      differ from each other in arterial compliance. CONCLUSION: The presence of
      psychiatric diagnoses is associated with reduced arterial compliance. A large
      study may be required to measure any specific affects of antipsychotics such as
      quetiapine and risperidone on compliance compared to controls.

PMID- 22377106
TI  - Community mobilization to reduce postpartum hemorrhage in home births in northern
      Nigeria.
AB  - The purpose of this study is to demonstrate the importance of community
      mobilization in the uptake of a health intervention, namely, community-based
      distribution of misoprostol to prevent postpartum hemorrhage. Community
      mobilization to increase access to misoprostol for postpartum hemorrhage
      prevention was implemented in northwestern Nigeria in 2009. Theories of community
      participation and the current near-epidemic maternal mortality conditions
      underpin an approach using modest levels of community involvement. The study was
      undertaken in five communities around Zaria, Nigeria. Community leaders and
      selected community members participated in a series of dialogs. Additionally,
      community education, information and dramas sessions were held. Twenty nine
      community oriented resource persons (CORPs), 27 drug keepers and 41 traditional
      birth attendants (TBAs) were involved in the intervention. Postpartum interviews
      were used to assess the impact of community mobilization efforts and to track use
      of misoprostol. Multiple logistic regression was used to examine the association
      between correct use and receiving information regarding misoprostol from TBAs or
      CORPs. A total of 1875 women were enrolled in the study in 2009. Most women
      delivered at home (95%) and skilled attendance at delivery was low (7%).
      Community mobilization efforts reached most women with information about
      postpartum hemorrhage and misoprostol (88%), resulting in high comprehension of
      intervention messages. Women identified TBAs and CORPs as the single most
      important source of information about misoprostol 41% and 31% of the time,
      respectively. Availability of misoprostol at the community level gave 79% of
      enrolled women some protection against postpartum hemorrhage which they otherwise
      would not have had. Although high level community participation in health care
      interventions is the ideal, this study suggests that even in circumstances where
      only modest levels of participation can realistically be achieved, community
      mobilization can have a significant impact on the successful distribution and
      uptake of a potentially life-saving health intervention, in turn helping promote
      policy change.

PMID- 22377109
TI  - Serologic evidence of nipah virus infection in bats, Vietnam.

PMID- 22377111
TI  - Surgery of the nose and paranasal sinuses: principles and concepts.

PMID- 22377115
TI  - World Nutrition 2012--a global Public Health Nutrition opportunity.

PMID- 22377117
TI  - Clinical significance of Escherichia albertii.
AB  - Discriminating Escherichia albertii from other Enterobacteriaceae is difficult.
      Systematic analyses showed that E. albertii represents a substantial portion of
      strains currently identified as eae-positive Escherichia coli and includes Shiga
      toxin 2f-producing strains. Because E. albertii possesses the eae gene, many
      strains might have been misidentified as enterohemorrhagic or enteropathogenic E.
      coli.

PMID- 22377120
TI  - Effect of leisure activities on inflammation and cognitive function in an aging
      sample.
AB  - Cardiovascular disease risk factors (CVDRFs) increase the risk of dementia. The
      purpose of this study was to examine whether leisure activities (mental,
      physical, and social activities) modified the effect of CVDRFs on inflammatory
      markers and cognitive function in middle and old age. A secondary-data analysis
      study was conducted using data from 405 middle-age participants (40-59 years) and
      342 old-age participants (60-84 years) who participated in the Survey of Midlife
      Development in the United States (MIDUS). CVDRFs were obtained from a combination
      of self-report medical history and blood-based biomarkers. Three CVDRF groups
      (<=1, 2, and >=3 CVDRFs) were identified. More CVDRFs were significantly
      associated with higher levels of inflammatory markers in both age groups, and
      associated with lower levels of executive function (EF) in the old age group.
      CVDRFs were not related to the frequency of leisure activities in either age
      group. After controlling for covariates, higher levels of physical activities
      were significantly associated with lower levels of inflammatory markers, and
      higher levels of mental activities were associated with higher levels of
      cognitive function. In the old age group, physical activities also moderated the
      effect of CVDRFs on episodic memory (EM), and mental activities moderated the
      effect of CVDRFs on interleukin-6 (IL-6). Multiple CVDRFs may be associated with
      poorer cognitive function and higher inflammatory markers, but middle-age and
      older adults with CVDRFs may not engage in frequent physical and cognitive
      activities that may be protective. It is important to develop strategies to
      facilitate engagement in these activities from midlife.

PMID- 22377122
TI  - A single amino acid in the helicase domain of PMMoV-S is responsible for its
      enhanced accumulation in C. chinense (L(3)L(3)) plants at 32 degrees C.
AB  - In Capsicum chinense (L(3)L(3)) plants a higher accumulation of the tobamovirus
      Pepper mild mottle virus strain S (PMMoV-S) as compared to the Italian strain
      PMMoV-I is detected when plants are grown at 32 degrees C. By using a reverse
      genetic approach, we have established that a single amino acid at position 898 in
      the helicase domain of the polymerase protein, outside of the conserved regions
      of the helicase, is critical for the higher accumulation of PMMoV-S observed. It
      also is necessary for both increased accumulation of viral RNA of both polarities
      in pepper protoplasts and enhanced cell-to-cell movement in C. chinense plants.
      The influence of thermoresistance of PMMoV-S, a P(1,2) pathotype, and its
      prevalence on pepper cultivars over PMMoV-I, a P(1,2,3), pathotype, is discussed.

PMID- 22377127
TI  - Inflammatory HER2-positive breast cancer.

PMID- 22377126
TI  - Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory
      HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study.
AB  - BACKGROUND: Bevacizumab and trastuzumab are efficacious for treatment of advanced
      or HER2-positive metastatic breast cancer; however, few data exist for this
      regimen in inflammatory breast cancer. In our phase 2 trial, we aimed to assess
      efficacy and safety of neoadjuvant bevacizumab combined with trastuzumab and
      chemotherapy in patients with primary HER2-positive inflammatory breast cancer.
      METHODS: In our phase 2, multicentre, open-label, single-arm, non-comparative
      trial, we enrolled women (aged >= 18 years) with histologically confirmed HER2
      positive non-metastatic inflammatory breast cancer at private or public oncology
      centres in France. Before surgery, patients were treated with fluorouracil,
      epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel,
      bevacizumab, and trastuzumab (cycles 5-8) in 3-week cycles. After surgery,
      patients received adjuvant radiotherapy, trastuzumab, and bevacizumab. For the
      primary endpoint, we assessed the proportion of patients who achieved a
      pathological complete response (defined by central review of surgical specimens
      according to Sataloff classification, counting missing data as failure) and
      adverse events in all enrolled patients. This study is registered with
      ClinicalTrials.gov, number NCT00717405. FINDINGS: Between Oct 23, 2008, and Oct
      28, 2009, we enrolled 52 patients at 21 centres. 42 (81%) of 52 patients received
      all eight cycles of neoadjuvant therapy and 49 (94%) underwent surgery. After
      neoadjuvant therapy, 33 of 52 patients had a pathological complete response
      according to central review (63.5%, 95% CI 49.4-77.5). The most common adverse
      events were asthenia and nausea (both occurred in 36 [69%] of 52 patients). 25
      (48%) patients had grade 3-4 neutropenia, which was the most common grade 3-4
      adverse event. Only one grade 3 or worse adverse event regarded as related to
      bevacizumab was reported (hypertension, one patient). Four patients (8%) had
      cardiac failure. INTERPRETATION: Neoadjuvant treatment with bevacizumab,
      trastuzumab, and chemotherapy was efficacious and well tolerated in patients with
      previously untreated primary inflammatory breast cancer. Further confirmation of
      use of bevacizumab in inflammatory breast cancer is needed. FUNDING: Roche
      (France).

PMID- 22377132
TI  - Discordance in Mycobacterium tuberculosis rifampin susceptibility.

PMID- 22377135
TI  - Chikungunya outbreak in Guangdong Province, China, 2010.
AB  - A disease outbreak with dengue-like symptoms was reported in Guangdong Province,
      China, in October 2010. Testing results confirmed that the pathogen causing the
      outbreak was chikungunya virus. Phylogenic analysis indicated that this virus was
      a member of the Indian Ocean clade of the East/Center/South African subgroup of
      chikungunya virus.

PMID- 22377136
TI  - Decreased repair of singlet oxygen-induced DNA damage in xeroderma pigmentosum
      group A cells determined by plasmid host cell reactivation.

PMID- 22377138
TI  - Expression of nonconscious knowledge via ideomotor actions.
AB  - Ideomotor actions are behaviours that are unconsciously initiated and express a
      thought rather than a response to a sensory stimulus. The question examined here
      is whether ideomotor actions can also express nonconscious knowledge. We
      investigated this via the use of implicit long-term semantic memory, which is not
      available to conscious recall. We compared accuracy of answers to yes/no
      questions using both volitional report and ideomotor response (Ouija board
      response). Results show that when participants believed they knew the answer,
      responses in the two modalities were similar. But when they believed they were
      guessing, accuracy was at chance for volitional report (50%), but significantly
      higher for Ouija response (65%). These results indicate that implicit semantic
      memory can be expressed through ideomotor actions. They also suggest that this
      approach can provide an interesting new methodology for studying implicit
      processes in cognition.

PMID- 22377139
TI  - Disowning one's seen real body during an out-of-body illusion.
AB  - Under normal circumstances, we experience that our center of awareness is located
      behind our eyes and inside our own body. To learn more about the perceptual
      processes that underlie this tight coupling between the spatial dimensions of our
      consciously perceived self and our physical body, we conducted a series of
      experiments using an 'out-of-body illusion'. In this illusion, the conscious
      sense of self is displaced in the testing room by experimental manipulation of
      the congruency of visual and tactile information and a change in the visual
      perspective. We demonstrate that when healthy individuals experience that they
      are located in a different place from their real body, they disown this body and
      no longer perceive it as part of themselves. Our findings are important because
      they reveal a relationship between the representation of self-location in the
      local environment and the multisensory representation of one's own body.

PMID- 22377140
TI  - Factors associated with the non-completion of conventional anti-tuberculosis
      treatment in Peru.
AB  - BACKGROUND: The non-adherence to tuberculosis treatment is associated with
      increased infection, antibiotic resistance, increased costs and death. Our
      objective was to identify factors associated with lack of completion of
      conventional treatment for tuberculosis in Peru. PATIENTS AND METHODS: An
      unmatched case-control study in patients diagnosed with tuberculosis from 2004
      2005 who completed treatment until September 2006. The cases were defined as
      patients who discontinued treatment for >=30 consecutive days, while the controls
      were defined as those who completed treatment without interruption. The factors
      were identified by logistic regression, calculating odds ratios (OR) and 95%
      confidence intervals (CI). RESULTS: We studied 265 cases and 605 controls. The
      non-adherence to treatment in our study was associated with the male sex
      (OR=1.62; CI: 1.07-2.44), having felt discomfort during treatment (OR=1.76; CI:
      1.19-2.62), a prior history of non-compliance (OR=7.95; CI: 4.76-13.27) and
      illegal drug use (OR=3.74; CI: 1.25-11.14). Also, if we consider the interaction
      of previous non-adherence history and poverty, the risk of non-completion
      increases (OR=11.24; CI: 4-31.62). Conversely, having been properly informed
      about the disease (OR=0.25; CI: 0.07-0.94) and being able to access health-care
      services within office hours (8 am-8 pm) (OR=0.52; CI: 0.31-0.87) were associated
      with better adherence. CONCLUSIONS: The non-compliance with anti-tuberculosis
      treatment was associated with non-modifiable factors (male sex, previous non
      compliance) and with others whose control would improve compliance (malaise
      during treatment, illegal drug use and poverty). Likewise, providing access to
      the health-care system and improving the information given about tuberculosis
      should be priorities.

PMID- 22377146
TI  - Occurrence of sulfonamide and tetracycline-resistant bacteria and resistance
      genes in aquaculture environment.
AB  - The occurrence of sulfonamide and tetracycline resistance and their pollution
      profile in the aquaculture environment of Tianjin, northern China, were
      investigated. The presence of antibiotic-resistant bacteria was identified and
      the corresponding antibiotic resistance genes (ARGs) were quantified at 6
      aquaculture farms in Tianjin. Sulfonamide-resistance genes were prevalent and
      their concentrations were the highest detected (3.0 * 10(-5) to 3.3 * 10(-4) for
      sul1/16S rDNA, 2.0 * 10(-4) to 1.8 * 10(-3) for sul2/16S rDNA) among the various
      ARGs, most likely because the use of sulfonamides is more prevalent than
      tetracyclines in this area. Bacillus was the most dominant bacterial genus in
      both sulfamethoxazole resistant bacteria (63.27% of the total resistant bacteria)
      and tetracycline-resistant bacteria (57.14% of the total resistant bacteria). At
      least two of those genes (tetM, tetO, tetT, tetW, sul1 and sul2) were detected in
      the isolates of Bacillus cereus, Bacillus subtilis, Bacillus megaterium and
      Acinetobacter lwofii, and all of the above genes were detected in B. cereus,
      suggesting the occurrence of multi-resistance in the studied area. The genetic
      transfer of sul1 between intestinal bacteria (e.g., Enterococcus spp.) and
      indigenous bacteria (e.g., Bacillus spp.) was implied by phylogenetic analysis.
      Several strains of resistant opportunistic pathogens (e.g., Acinetobacter spp.)
      were found in indigenous bacteria, which increase the risk of ARGs to public
      health. Overall, this is the first study to comprehensively investigate the
      antibiotic resistance profile by analyzing the species of antibiotic-resistant
      bacteria and adopting qualitative and quantitative methods to investigate ARGs at
      a typical aquaculture area in northern China.

PMID- 22377147
TI  - Delivery and impact bypass in a karst aquifer with high phosphorus source and
      pathway potential.
AB  - Conduit and other karstic flows to aquifers, connecting agricultural soils and
      farming activities, are considered to be the main hydrological mechanisms that
      transfer phosphorus from the land surface to the groundwater body of a karstified
      aquifer. In this study, soil source and pathway components of the phosphorus (P)
      transfer continuum were defined at a high spatial resolution; field-by-field soil
      P status and mapping of all surface karst features was undertaken in a > 30 km(2)
      spring contributing zone. Additionally, P delivery and water discharge was
      monitored in the emergent spring at a sub-hourly basis for over 12 months.
      Despite moderate to intensive agriculture, varying soil P status with a high
      proportion of elevated soil P concentrations and a high karstic connectivity
      potential, background P concentrations in the emergent groundwater were low and
      indicative of being insufficient to increase the surface water P status of
      receiving surface waters. However, episodic P transfers via the conduit system
      increased the P concentrations in the spring during storm events (but not >0.035
      mg total reactive P L(-1)) and this process is similar to other catchments where
      the predominant transfer is via episodic, surface flow pathways; but with high
      buffering potential over karst due to delayed and attenuated runoff. These data
      suggest that the current definitions of risk and vulnerability for P delivery to
      receiving surface waters should be re-evaluated as high source risk need not
      necessarily result in a water quality impact. Also, inclusion of conduit flows
      from sparse water quality data in these systems may over-emphasise their
      influence on the overall status of the groundwater body.

PMID- 22377149
TI  - An exploration of the association between male body mass index and semen quality.

PMID- 22377150
TI  - Characterization of a recurrent poor-quality embryo morphology phenotype and
      zygote transfer as a rescue strategy.
AB  - Some patients in IVF programmes repeatedly display an abnormal embryonic
      development characterized as soon as day 2 post fertilization by a high rate
      (>60%) of highly fragmented embryos (?40% of cytoplasmic fragments) leading to
      recurrent IVF failures. This study postulated that, for various maternal reasons,
      some embryos were unable to withstand the in-vitro environment and an early
      pronucleate-stage transfer was proposed to these couples. Fifty-three patients
      with recurrent IVF failures (a mean of 2.8+/-1.0 previous attempts) characterized
      by low embryonic quality (a mean of 62.7% of the embryos with extended
      fragmentation) were included this transfer protocol. As in previous cycles, the
      mean number of oocytes retrieved and the fertilization rate were normal. The mean
      number of zygotes per transfer was 2.24. Fourteen clinical pregnancies were
      obtained, representing a pregnancy rate and a delivery rate per oocyte retrieval
      of 26.4% and 18.9%, respectively. Recurrent heavy and early embryo fragmentation
      in vitro characterizes around 3% of IVF couples and leads to lack of transfer or
      implantation failure. These data on fresh zygote transfers are encouraging and
      may provide a valid alternative solution for some of these patients. Some
      patients in IVF programmes repeatedly display an abnormal embryonic development
      characterized as soon as day 2 post fertilization by a high rate of highly
      fragmented embryos, leading to recurrent IVF failures. We hypothesized that, for
      various reasons, some embryos were unable to withstand the in-vitro environment
      and an early pronucleate stage transfer was proposed to these couples. Fifty
      three patients with recurrent IVF failures characterized by low embryonic quality
      were included in this transfer protocol. As in previous cycles, the mean number
      of oocytes retrieved and the fertilization rate were normal. The mean number of
      zygotes per transfer was 2.24. Fourteen clinical pregnancies were obtained,
      representing a pregnancy rate and a delivery rate per oocyte retrieval of 26.4%
      and 18.9%, respectively. Recurrent early and heavy embryo fragmentation in vitro
      characterizes around 3% of IVF couples and leads to lack of transfer or
      implantation failure. Our data on fresh zygote transfers are encouraging and may
      provide a valid alternative solution for these patients.

PMID- 22377151
TI  - Polymorphisms in DLGH1 and LAMC1 in Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Mullerian agenesis, also termed the Mayer-Rokitansky-Kuster-Hauser syndrome
      (MRKHS) is a disorder with an incidence of approximately 1 in 4500 newborn girls.
      This study screened 12 patients with MRKHS for mutations in two genes, LAMC1 and
      DLGH1, involved in the development of Mullerian structures and found 10
      previously described variants and no novel variants in the coding sequence. It is
      highly unlikely that these variants are pathological since these are common in
      the general population. It is the first time that an extensive study of LAMC1 and
      DLGH1 has been undertaken in patients with MRKHS. The data support the notion
      that mutations in the coding sequence of LAMC1 and DLGH1 may not be associated
      with MRKHS.

PMID- 22377152
TI  - A case-control pilot study of low-intensity IVF in good-prognosis patients.
AB  - Low-intensity IVF (LI-IVF) is rapidly gaining in popularity. Yet studies
      comparing LI-IVF to standard IVF are lacking. This is a case-control pilot study,
      reporting on 14 first LI-IVF and 14 standard IVF cycles in women with normal age
      specific ovarian reserve under age 38, matched for age, laboratory environment,
      staff and time of cycle. LI-IVF cycles underwent mild ovarian stimulation,
      utilizing clomiphene citrate, augmented by low-dose gonadotrophin stimulation.
      Control patients underwent routine ovarian stimulation. LI-IVF and regular IVF
      patients were similar in age, body mass index, FSH and anti-Mullerian hormone.
      Standard IVF utilized more gonadotrophins (P<0.001), yielded more oocytes
      (P<0.001) and cryopreserved more embryos (P<0.001). With similar embryo numbers
      transferred, after ethnicity adjustments, standard IVF demonstrated better odds
      for pregnancy (OR 7.07; P=0.046) and higher cumulative pregnancy rates (63.3%
      versus 21.4%; OR 6.6; P=0.02). Adjustments for age, ethnicity and diagnosis
      maintained significance but oocyte adjustment did not. Cost assessments failed to
      reveal differences between LI-IVF and standard IVF. In this small study, LI-IVF
      reduced pregnancy chances without demonstrating cost advantages, raising
      questions about its utility. In the absence of established clinical and/or
      economic foundations, LI-IVF should be considered an experimental procedure. Low
      intensity IVF (LI-IVF) is increasingly propagated as an alternative to standard
      IVF. LI-IVF has, however, never been properly assessed in comparison to standard
      IVF. Such a comparison is presented in the format of a small pilot study,
      matching LI-IVF cycles with regular IVF cycles and comparing outcomes as well as
      costs. The study suggests that LI-IVF, at least in this setting, is clinically
      inferior and economically at best similar to standard IVF. LI-IVF should,
      therefore, as of this point not be offered as routine IVF treatment but only as
      an experimental procedure.

PMID- 22377153
TI  - Elevated progesterone during ovarian stimulation for IVF.
AB  - There is an ongoing debate regarding the impact of premature progesterone rise on
      the IVF outcome. The objective of this review is to assess evidence of poorer
      ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end
      of follicular phase in ovarian stimulation. It also explores the origin of the
      progesterone rise, potential modifying factors and possible methods to prevent
      its rise during ovarian stimulation. This review draws on information already
      published from monitoring progesterone concentrations at the end of follicular
      phase in ovarian stimulation. The databases of Medline and PubMed were searched
      to identify relevant publications. Good-quality evidence supports the negative
      impact on endometrial receptivity of elevated progesterone concentrations at the
      end of the follicular phase in ovarian stimulation. Future trials should document
      the cause and origin of premature progesterone in stimulated IVF cycles. There is
      an ongoing debate regarding the impact of premature progesterone rise on the IVF
      outcome. The objective of this review is to assess evidence of poorer ongoing
      pregnancy rate in IVF cycles with elevated serum progesterone at the end of
      follicular phase in ovarian stimulation. It also explores the origin of the
      progesterone rise, potential modifying factors and possible methods to prevent
      its rise during ovarian stimulation. This review draws on information already
      published from monitoring progesterone concentrations at the end of follicular
      phase in ovarian stimulation. The databases of Medline and PubMed were searched
      to identify relevant publications. Good-quality evidence supports the negative
      impact on endometrial receptivity of elevated progesterone concentrations at the
      end of follicular phase in ovarian stimulation. Future trials should document the
      cause and origin of premature progesterone in stimulated IVF cycles.

PMID- 22377154
TI  - Gender incidence of intracytoplasmic morphologically selected sperm injection
      derived embryos: a prospective randomized study.
AB  - The aim of this prospective randomized study was to determine if the use of
      intracytoplasmic morphologically selected sperm injection (IMSI) is associated
      with gender incidence. Couples who underwent IVF-preimplantation genetic
      screening (PGS) cycles, as a result of advanced maternal age, were randomly
      allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80) or
      intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The
      incidences of genders were compared between ICSI- and IMSI-derived embryos.
      Considering all the biopsied embryos were characterized as normal for sex
      chromosome, the results showed that IMSI results in a significantly higher
      incidence of female embryos as compared with ICSI (65.1% versus 54.0%,
      respectively, P=0.0277). After analysing only euploid embryos for the eight
      selected chromosomes, a significantly higher incidence of XX embryos derived from
      IMSI was also observed compared with ICSI cycles (66.9% versus 52.5%,
      respectively, P=0.0322). This result was confirmed by logistic regression, which
      demonstrated a nearly 2-fold increase in euploid XX embryos derived from
      spermatozoa selected by high magnification (OR 1.83, 95% CI 1.05-3.35, P=0.032).
      A higher proportion of morphologically normal spermatozoa analysed under high
      magnification seem to carry the X chromosome. The aim of this study was to
      determine if the use of intracytoplasmic morphologically selected sperm injection
      (IMSI) is associated with gender incidence. Couples who underwent IVF with
      preimplantation genetic screening, as a result of advanced maternal age, were
      randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80)
      or intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The
      incidences of genders were compared between ICSI- and IMSI-derived embryos. Our
      results showed that a significantly higher incidence of female embryos derived
      from IMSI compared with ICSI cycles (66.9% versus 52.5%, respectively, P=0.0322).
      This result was confirmed by logistic regression, which demonstrated a nearly 2
      fold increase in female embryos derived from sperm selected by high magnification
      (OR 1.83, 95% CI 1.05-3.35, P=0.032). A higher proportion of morphologically
      normal spermatozoa analysed under high magnification seem to carry the X
      chromosome.

PMID- 22377155
TI  - Effect of patient selection on estimate of reproductive success after surgery for
      rectovaginal endometriosis: literature review.
AB  - The effect of rectovaginal endometriosis on fertility is unclear. Several authors
      foster radical surgery, including colorectal resection, as a fertility-enhancing
      procedure. However, interpretation of data is difficult, as the baseline
      fertility status is often undefined and it is not always possible to discriminate
      between spontaneous conceptions and those resulting from IVF. A systematic
      literature review was performed with the aim of defining the pregnancy rate
      specifically in patients who were infertile before surgery and who sought
      spontaneous pregnancy. A PubMed search was conducted to identify English language
      studies published between 2005 and 2011 evaluating reproductive performance after
      surgery for rectovaginal and rectosigmoid endometriosis. According to the results
      of the 11 selected studies, the mean post-operative conception rate in all women
      seeking pregnancy independently of preoperative fertility status and IVF
      performance was 39% (95% CI 35-43%; 223/571), but dropped to 24% (95% CI 20-28%;
      123/510) in infertile patients who sought spontaneous conception (odds ratio
      0.50, 95% CI 0.38-0.65%). Patients' selection significantly influences the
      estimate of the effect of rectovaginal endometriosis excision on infertility.
      This should be carefully taken into consideration at preoperative counselling.
      Rectovaginal endometriosis usually is associated with pain symptoms, but the
      effect of this disease form on fertility is uncertain, as burial of foci beneath
      rectouterine adhesions with exclusion of the deepest part of the pelvis may limit
      interference with fertilization processes. Several authors foster radical
      surgery, including colorectal resection, as a fertility-enhancing procedure.
      However, interpretation of data is difficult, as the baseline fertility status is
      often undefined and it is not always possible to discriminate between spontaneous
      conceptions and those resulting from IVF. A systematic literature review was
      performed with the aim of defining the pregnancy rate specifically in patients
      who were infertile before surgery and who sought pregnancy spontaneously. A
      PubMed search was conducted to identify English language studies published
      between 2005 and 2011 evaluating reproductive performance after surgery for
      rectovaginal and rectosigmoid endometriosis. According to the results of the 11
      selected studies, the mean post-operative conception rate in all women seeking
      pregnancy independently of preoperative fertility status and IVF performance was
      39% (223/571), but dropped to 24% (123/510) in infertile patients who sought
      conception spontaneously. The 15% difference is statistically significant.
      Infertile patients with rectovaginal endometriosis considering surgery, should be
      carefully informed of the real probability of post-operative conception avoiding
      generic overestimations.

PMID- 22377163
TI  - Production of piglets from in vitro-produced embryos following non-surgical
      transfer.
AB  - The objective of this study was to enhance procedures for producing piglets
      derived from in vitro-produced (IVP) pig embryos by non-surgical embryo transfer
      (ET). The effects of insertion length for the catheter, asynchrony between the
      age of donor IVP blastocysts and the recipient estrous cycle, and volume of
      transfer medium were investigated. The IVP blastocysts at 5 days after in vitro
      fertilization were placed into porcine zygote medium (PZM)-5 supplemented with
      10% (v/v) fetal bovine serum (PZM+FBS) in a 0.25 mL plastic straw (21-40
      blastocysts per straw) and then transferred into one uterine horn of recipients
      using the Takumi((r)) catheter for deep intrauterine insertion. Successful
      production of piglets derived from IVP embryos was achieved following non
      surgical ET when the catheter was inserted at more than 30 cm anterior to the
      spiral guide spirette. The efficiency of piglet production (percentage number of
      piglet(s) born based on the number of embryos transferred) was greater (P<0.05)
      in recipients whose estrous cycle was asynchronous to that of donors with a 1-day
      delay (8.3%) than in those with a 2-day (1.5%) or 3-day (0.9%) delay, while
      pregnancy and farrowing rates (10-40%) did not differ among treatments. When
      blastocysts were transferred into recipients with 1.0 or 2.5 mL PZM+FBS, there
      were no significant differences in farrowing rate (30-40%) or average litter size
      (4.5-6.7) between treatments. The results of the present study indicate that the
      insertion length of the deep intrauterine catheter and the degree of asynchrony
      between donor embryos and recipient estrous cycle influenced on pregnancy and
      birth outcome following non-surgical transfer of IVP blastocysts.

PMID- 22377159
TI  - Occurrence, transmission, and zoonotic potential of chronic wasting disease.
AB  - Chronic wasting disease (CWD) is a fatal, transmissible prion disease that
      affects captive and free-ranging deer, elk, and moose. Although the zoonotic
      potential of CWD is considered low, identification of multiple CWD strains and
      the potential for agent evolution upon serial passage hinders a definitive
      conclusion. Surveillance for CWD in free-ranging populations has documented a
      continual geographic spread of the disease throughout North America. CWD prions
      are shed from clinically and preclinically affected hosts, and CWD transmission
      is mediated at least in part by the environment, perhaps by soil. Much remains
      unknown, including the sites and mechanisms of prion uptake in the naive host.
      There are no therapeutics or effective eradication measures for CWD-endemic
      populations. Continued surveillance and research of CWD and its effects on cervid
      ecosystems is vital for controlling the long-term consequences of this emerging
      disease.

PMID- 22377165
TI  - High incidence of group B streptococcal infection in infants born to HIV-infected
      mothers.

PMID- 22377167
TI  - Drug-resistant tuberculosis in Zhejiang Province, China, 1999-2008.
AB  - To evaluate levels and trends in drug-resistant tuberculosis (TB) in Zhejiang
      Province, China, we conducted 1 survey in each of 3 years (1999, 2004, and 2008).
      We found that <5% of new cases were multidrug-resistant TB. The prevalence of
      multidrug-resistant TB has not increased in new or re-treated cases in this
      province.

PMID- 22377171
TI  - Quick guide to polyketide synthase and nonribosomal synthetase genes in Fusarium.
AB  - Fusarium species produce a plethora of bioactive polyketides and nonribosomal
      peptides that give rise to health problems in animals and may have drug
      development potential. Using the genome sequences for Fusarium graminearum, F.
      oxysporum, F. solani and F. verticillioides we developed a framework for future
      polyketide synthases (PKSs) and nonribosomal peptides synthetases (NRPSs)
      nomenclature assignment and classification. Sequence similarities of the
      adenylation and ketosynthase domain sequences were used to group the identified
      NRPS and PKS genes. We present the current state of knowledge of PKS and NRPS
      genes in sequenced Fusarium species and their known products. With the rapid
      increase in the number of sequenced fungal genomes a systematic classification
      will greatly aid the scientific community in obtaining an overview of the number
      of different NRPS and PKS genes and their potential as producers of known
      bioactive compounds.

PMID- 22377172
TI  - Predicting EDC concentrations in a river mixing zone.
AB  - The fate and transport of endocrine disrupting chemicals (EDCs) in ambient river
      waters is a major concern associated with effluents from municipal wastewater
      treatment plants (WWTPs). This paper presents a methodology for quantifying the
      spatial distribution of EDCs in a river mixing zone. The core of the technical
      analysis is based on a two-dimensional steady-state analytical model
      characterized by ambient turbulence in the receiving water. This model was first
      calibrated with mass transport data from field measurements for a conservative
      substance (electrical conductivity) and then used to predict aqueous-phase EDC
      concentrations throughout a WWTP mixing zone. To demonstrate the usefulness of
      this methodology for water quality management purposes, the modeling framework
      presented in this paper was used to determine a lumped in-stream attenuation rate
      constant (k(d)=3 d(-1)) for 17beta-estradiol under natural conditions. This rate
      constant likely accounts for the combined contributions of physical sorption,
      photolysis, microbial and chemical degradation, and the measured value is highly
      consistent with previously published results from bench-scale removal
      experiments.

PMID- 22377173
TI  - Electrogeneration of H(2) for Pd-catalytic hydrodechlorination of 2,4
      dichlorophenol in groundwater.
AB  - A novel electrolytic groundwater remediation process, which used the H(2)
      continuously generated at cathode to achieve in situ catalytic
      hydrodechlorination, was developed for the treatment of 2,4-dichlorophenol (2,4
      DCP) in groundwater. Catalytic hydrodechlorination using Pd supported on bamboo
      charcoal and external H(2) showed that 2,4-DCP was completely dechlorinated to
      phenol within 30 min at pH <= 5.5. In a divided electrolytic system, the
      catalytic hydrodechlorination of 2,4-DCP in cathodic compartment by H(2)
      generated at the cathode under 20 and 50 mA reached 100% at 120 and 60 min,
      respectively. Two column experiments with influent pHs of 5.5 (unconditioned) and
      2 were conducted to evaluate the feasibility of this process. The 2,4-DCP removal
      efficiencies were about 63% and nearly 100% at influent pHs of 5.5 and 2,
      respectively. Phenol was solely produced by 2,4-DCP hydrodechlorination, and was
      subsequently degraded at the anode. A low pH could enhance the
      hydrodechlorination, but was not necessarily required. This study provides the
      preliminary results of a novel effective electrolytic process for the remediation
      of groundwater contaminated by chlorinated aromatics.

PMID- 22377177
TI  - Foodborne and waterborne infections in elderly community and long-term care
      facility residents,Victoria, Australia.
AB  - We calculated rates of foodborne and waterborne infections reported to the health
      department in Victoria, Australia, during 2000-2009 for elderly residents of long
      term care facilities (LTCFs) and the community. We used negative binomial
      regression to estimate incidence rate ratios, adjusting for age, sex, and
      reporting period. We analyzed 8,277 infections in elderly persons. Rates of
      campylobacteriosis, legionellosis, listeriosis, toxigenic Escherichia coli
      infections, and shigellosis were higher in community residents, and rates of
      Salmonella infection were higher in LTCF residents. Each year, 61.7 Campylobacter
      infections were reported per 100,000 LTCF residents, compared with 97.6 per
      100,000 community residents. LTCF residents were at higher risk for S. enterica
      serotype Typhimurium associated with outbreaks. Rates of foodborne infections
      (except salmonellosis) were similar to or lower for LTCF residents than for
      community residents. These findings may indicate that food preparation practices
      in LTCFs are safer than those used by elderly persons in the community.

PMID- 22377179
TI  - What does the future hold for patients with epilepsy?

PMID- 22377180
TI  - Prognostic factors for time to treatment failure and time to 12 months of
      remission for patients with focal epilepsy: post-hoc, subgroup analyses of data
      from the SANAD trial.
AB  - BACKGROUND: Epilepsy is a heterogeneous disorder, with outcomes ranging from
      immediate remission after taking a first antiepileptic drug to frequent
      unremitting seizures with multiple treatment failures. Few prognostic models
      enable prediction of outcome; we therefore aimed to use data from the SANAD study
      to predict outcome overall and for patients receiving specific treatments.
      METHODS: The SANAD study was a randomised controlled trial in which standard
      antiepileptic drugs were compared with new treatments. Arm A included patients
      for whom carbamazepine was considered the first-line treatment, most of whom were
      newly diagnosed with focal epilepsy. Patients were randomly assigned to receive
      carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes
      were time to treatment failure overall, because of inadequate seizure control,
      and because of adverse events, and time to 12 months of remission from seizures.
      In this post-hoc study we used regression multivariable modelling to investigate
      how clinical factors affect the probability of treatment failure and the
      probability of achieving 12 months of remission. FINDINGS: For time to treatment
      failure, we identified several significant risk factors: sex (male vs female,
      hazard ratio [HR] 0.86, 95% CI 0.75-0.99), treatment history (taking non-SANAD
      antiepileptic drugs [other than those listed above] vs treatment naive, 1.27,
      1.05-1.53), age (eg, older than 71 years vs 10 years or younger, 0.68, 0.51
      0.91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1.08,
      1.05-1.11), electroencephalogram results (epileptiform abnormality vs normal,
      1.26, 1.07-1.50), seizure type (eg, secondary generalised vs simple or complex
      partial only, 0.78, 0.66-0.91), site of onset (not localised vs temporal lobe,
      1.25, 1.06-1.47), and treatment (lamotrigine vs carbamazepine, 0.76, 0.61-0.95).
      Significant factors for time to 12 months of remission were sex (male vs female,
      1.19, 1.05-1.35), treatment history (taking a non-SANAD antiepileptic drug vs
      treatment naive, 0.64, 0.52-0.78), age (eg, older than 71 years vs 10 years or
      younger, 1.60, 1.26-2.03), time from first seizure (60-239 months vs >=2 months,
      1.14, 1.01-1.29; >240 months vs <=2 months, 1.39, 1.04-1.86), neurological insult
      (present vs absent, 0.75, 0.61-0.93), total number of seizures before
      randomisation (eg, four to 11 vs two or fewer, 0.87, 0.85-0.90), and treatment
      (gabapentin vs carbamazepine, 0.71, 0.59-0.86; topiramate vs carbamazepine, 0.81,
      0.68-0.98). INTERPRETATION: We present a thorough investigation of prognostic
      factors from a large randomised controlled trial in patients starting
      antiepileptic monotherapy. If validated, our models could aid in individual
      patient risk stratification and the design and analysis of epilepsy trials.
      FUNDING: National Institute for Health Research (UK).

PMID- 22377181
TI  - Case report of left atrial appendageal tuberculosis.

PMID- 22377182
TI  - A rare cause of fatal right ventricular cardiac decompensation.
AB  - Hereditary hemorrhagic telangiectasia is an autosomal dominant vascular disease
      often manifesting with epistaxis, telangiectasia, and intraparenchymatous
      arteriovenous malformations. We report on the case of a 71-year-old man who was
      admitted to hospital due to a tricuspid valve insufficiency. During the following
      days, the patient developed liver and renal failure; the clinical condition
      worsened rapidly. Computed tomographic diagnostics revealed arteriovenous
      malformations in the lung and in the liver portal. Additionally, mucocutaneous
      telangiectasia in the mouth was found. Hereditary hemorrhagic telangiectasia was
      assumed; nevertheless, an effective treatment was impossible because of the
      patient's worse clinical state; he died a few days later. Autopsy affirmed the
      diagnosis of hereditary hemorrhagic telangiectasia; molecular genetic analysis
      revealed a heterozygous mutation in the ALK-1 gene. Despite its relatively high
      prevalence, hereditary hemorrhagic telangiectasia is not considered as a
      diagnosis as frequently as it should be, and clinicians need to be aware of the
      signs of hereditary hemorrhagic telangiectasia as well as the appropriate
      diagnostic workup.

PMID- 22377185
TI  - Corticotropin releasing factor (CRF) and obesity.

PMID- 22377186
TI  - Incidence of uterine leiomyosarcoma and endometrial stromal sarcoma in Nordic
      countries: results from NORDCAN and NOCCA databases.
AB  - OBJECTIVES AND STUDY DESIGN: Uterine sarcomas are an uncommon and heterogeneous
      group of malignancies. Their etiology is mainly unknown. Here, we analyzed trends
      in incidence and occupational variation in risk of uterine leiomyosarcomas (LMS)
      and endometrial stromal sarcomas (ESS) in the Nordic countries aided by NORDCAN
      and NOCCA (Nordic Occupational Cancer) databases. MAIN OUTCOME MEASURES:
      Incidence rates per 100,000 and Standardized incidences rates (SIR) obtained from
      NORDCAN and NOCCA databases. RESULTS: The incidence rates were about 0.3 per
      100,000 for ESS and about 0.4 per 100,000 for LMS in Denmark, Finland, Iceland,
      and Norway. During the study-period (1978-2007), the incidence rates in each
      country were quite similar and constant. The age-specific incidence of LMS showed
      a peak around menopause. Significantly increased risk for LMS occurred in shoe
      and leather workers, farmers and teachers, whereas significantly low risk was
      detected with packers in the NOCCA data from Finland, Norway, and Sweden. For ESS
      no occupations showed either increased or decreased incidences. CONCLUSIONS: The
      incidence trends of LMS and ESS in our study were constant in four Nordic
      countries over time. The elevated risk for LMS with women exposed to leather work
      and animal dust indicates further exploration.

PMID- 22377187
TI  - Effective and clinically meaningful non-hormonal hot flash therapies.
AB  - Although many non-hormonal compounds have shown statistically significant benefit
      over placebo in hot flash randomized controlled trials (RCTs), these studies have
      varied considerably in basic methodology making it challenging to deduce which
      compounds have the greatest potential to provide clinically meaningful benefit.
      This review used evidence-based methodology closely mirroring the FDA and EMEA
      guidelines as a template to identify "well-designed" RCTs from which effective
      and clinically meaningful non-hormonal hot flash therapies could be identified.
      In addition, pertinent safety information was reviewed. Out of 3548 MEDLINE
      citations and abstracts, 51 well-designed hot flash RCTs were identified. From
      these trials, gabapentin, oxybutynin ER, desvenlafaxine, soy-derived isoflavones
      and black cohosh each showed a clinically meaningful treatment effect in at least
      1 RCT. Among these 5 compounds, only gabapentin demonstrated consistent and
      statistically significant benefit over placebo in all of its well-designed RCTs.
      Desvenlafaxine, soy-derived isoflavones, and black cohosh demonstrated
      statistically significant benefit over placebo in 75%, 21%, and 17% of the well
      designed RCTs for each compound, respectively. There was only 1 well-designed RCT
      using oxybutynin ER, which showed it to have a robust and clinically meaningful
      benefit. In terms of safety, there have been cardiovascular risks associated with
      desvenlafaxine use in postmenopausal women with hot flashes. The use of
      anticonvulsants, in general, has been associated with an absolute 0.21% increase
      in suicidal thoughts and behavior. Further research is needed with several of
      these nonhormonal compounds to replicate these findings and to also directly
      compare their efficacy and tolerability with those of hormone replacement
      therapy.

PMID- 22377193
TI  - Hippocampus-specific deletion of tissue plasminogen activator "tPA" in adult mice
      impairs depression- and anxiety-like behaviors.
AB  - Anxiety and depression are multifactorial disorders that have become prominent
      health problems all over the world. Neurotrophic factors have emerged underlying
      pathogenesis of these diseases. Although a number of studies indicate that the
      hippocampus-brain-derived neurotrophic factor (BDNF) may be involved in these
      psychiatric illnesses, little is known about the molecular mediators of these
      disorders. In this study we further investigate the role of tissue plasminogen
      activator (tPA), a serine protease involved in pro-BDNF cleavage to BDNF, in
      depression and anxiety-like behaviors in adult mice. To address this issue, we
      investigated the effect of hippocampus tPA manipulation, using viral vectors, on
      anxiety- and depression-like behaviors, including the marble burying test (MBT),
      elevated plus maze (EPM), tail suspension test (TST), novelty suppressed feeding
      (NSF) and forced swim test (FST). Our results showed that tPA knock-down - using
      lentiviral vectors expressing specific short hairpin RNAs (LV-shRNA) - increased
      the number of buried marbles together with the digging time in the MBT and
      decreased the time spent in open the arms of an EPM. In addition, tPA-knock down
      in the hippocampus increased immobility in the FST and TST, and increased time to
      feed in the NSF test. These effects were reversed when tPA-over-expressing
      vectors (LV-tPA) were injected in the hippocampus. We also found that BDNF
      protein levels were elevated in the hippocampus of mice receiving tPA-expressing
      vectors. Together, our results imply that tPA manipulation may provide an
      effective therapeutic intervention for depression and anxiety disorders.

PMID- 22377194
TI  - Etymology of cholera.

PMID- 22377196
TI  - Southeast Asian foot-and-mouth disease viruses in Eastern Asia.
AB  - Foot-and-mouth disease (FMD) outbreaks recently affected 2 countries (Japan and
      South Korea) in eastern Asia that were free of FMD without vaccination. Analysis
      of viral protein 1 nucleotide sequences indicated that FMD serotype A and O
      viruses that caused these outbreaks originated in mainland Southeast Asia to
      which these viruses are endemic.

PMID- 22377198
TI  - Factors determining success in percutaneous revascularization of chronic total
      coronary occlusion: multidetector computed tomography analysis.
AB  - INTRODUCTION AND OBJECTIVES: Percutaneous revascularization of chronic total
      coronary artery occlusion is a technical challenge and has a lower success rate
      than other angioplasty procedures. Identification of predictors of failure could
      lead to better selection of patients with the greatest possibility of success. In
      this study, we investigate the multidetector computed tomography features
      associated with failure of percutaneous treatment for chronic total coronary
      occlusion. METHODS: This is a prospective, single-center study of 69 consecutive
      patients with chronic total occlusion in whom multidetector computed tomography
      study was performed before percutaneous coronary revascularization. RESULTS:
      Seventy-seven lesions were analyzed. The mean length of the occlusion was 19.9
      (14.3) mm and the estimated duration of occlusion was 47 (62) months. The only
      angiographic factor independently predictive of failure was a severe curve
      between the plaque and the proximal patent vessel (odds ratio 3.8, 95% confidence
      interval, 1.2-12; P=.02). On multidetector computed tomography, the only factor
      predictive of failure was an arc of calcium affecting more than 50% of the vessel
      circumference in the proximal (P=.04) and middle (P=.03) third of the occlusion.
      CONCLUSIONS: Multidetector computed tomography identified a variable that cannot
      be measured by angiography that can predict failure in percutaneous
      revascularization of chronic total coronary occlusions. In selected cases, this
      parameter could be useful for preprocedure screening.

PMID- 22377199
TI  - Management of a hypersensitivity reaction to thienopyridines: prasugrel-induced
      fever and hepatitis resolved after switching to clopidogrel.

PMID- 22377202
TI  - Nonpasteurized dairy products, disease outbreaks, and state laws-United States,
      1993-2006.
AB  - Although pasteurization eliminates pathogens and consumption of nonpasteurized
      dairy products is uncommon, dairy-associated disease outbreaks continue to occur.
      To determine the association of outbreaks caused by nonpasteurized dairy products
      with state laws regarding sale of these products, we reviewed dairy-associated
      outbreaks during 1993-2006. We found 121 outbreaks for which the product's
      pasteurization status was known; among these, 73 (60%) involved nonpasteurized
      products and resulted in 1,571 cases, 202 hospitalizations, and 2 deaths. A total
      of 55 (75%) outbreaks occurred in 21 states that permitted sale of nonpasteurized
      products; incidence of nonpasteurized product-associated outbreaks was higher in
      these states. Nonpasteurized products caused a disproportionate number (~150*
      greater/unit of product consumed) of outbreaks and outbreak-associated illnesses
      and also disproportionately affected persons <20 years of age. States that
      restricted sale of nonpasteurized products had fewer outbreaks and illnesses;
      stronger restrictions and enforcement should be considered.

PMID- 22377204
TI  - Inter-tibiofibular graft for traumatic segmental bone defect of the tibia.
AB  - INTRODUCTION: The present study sought to assess the interest of inter
      tibiofibular graft (ITFG), alternatively called posterolateral bone graft, in
      traumatic segmental tibial bone defect. MATERIAL AND METHODS: Twenty-eight ITFGs
      were performed in 125 tibial reconstructions for traumatic bone defect. Patient's
      records were reviewed retrospectively in a multicenter study. Tibial
      reconstruction with and without ITFG was compared for bone healing and patient's
      return to full weight-bearing status. RESULTS: There were no failures of bone
      healing in the ITFG group, versus 14 (14%) in the non-ITFG group. Graft-to
      consolidation delays were shorter with first-line ITFG, at a mean 10 months
      (range, 3-20 months) versus 16.5 months (range, 3-63 months) in the non-ITFG
      group (P<0.05). Weight-bearing was likewise more quickly resumed, with full
      weight-bearing at a mean 9 months (range, 3-19 months) versus 15 months (range, 1
      34 moths) respectively (P<0.05). Return to work was also quicker, at a mean 15
      months (range, 4-28 months) versus 27 months (range, 8-56 months) respectively
      (P<0.05). DISCUSSION: This study confirmed the interest of ITFG in tibial bone
      defect reconstruction. ITFG may singly be used for small defects less than 4 cm,
      or in conjunction with another tibial reconstruction technique; ITFG in the
      present series achieved consolidation in all cases and significantly shortened
      the times to return to full weight-bearing status and to work. LEVEL OF EVIDENCE:
      III: retrospective case-control study.

PMID- 22377214
TI  - Metal chelate affinity precipitation: purification of BSA using poly(N
      vinylcaprolactam-co-methacrylic acid) copolymers.
AB  - This investigation involves the metal chelate affinity precipitation of bovine
      serum albumin (BSA) using a copper ion loaded thermo-sensitive copolymer. The
      copolymer of N-vinylcaprolactam with methacrylic acid PNVCL-co-MAA was
      synthesized by free radical polymerization in aqueous solution, and Cu(II) ions
      were attached to provide affinity properties for BSA. A maximum loading of 48.1mg
      Cu(2+) per gram of polymer was attained. The influence of pH, temperature, BSA
      and NaCl concentrations on BSA precipitation and of pH,
      ethylenediaminetetraacetic acid (EDTA) and NaCl concentrations on elution were
      systematically probed. The optimum conditions for BSA precipitation occurred when
      pH, temperature and BSA concentration were 6.0, 10 degrees C and 1.0 mg/ml,
      respectively and the most favorable elution conditions were at pH 4.0, with 0.2M
      NaCl and 0.06 M EDTA. The maximum amounts of BSA precipitation and elution were
      37.5 and 33.7 mg BSA/g polymer, respectively. It proved possible to perform
      multiple precipitation/elution cycles with a minimal loss of polymer efficacy.
      The results show that PNVCL-co-MAA is a suitable matrix for the purification of
      target proteins from unfractionated materials.

PMID- 22377215
TI  - Cytostatic effect of xanthone-loaded mPEG-b-p(HPMAm-Lac2) micelles towards
      doxorubicin sensitive and resistant cancer cells.
AB  - Xanthone exhibits several medicinal activities and especially it inhibits the
      growth of cancer cells. However, the use of xanthone is limited because of its
      low aqueous solubility and systemic toxicity. In the present study xanthone was
      loaded into poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide
      dilactate] mPEG-b-p(HPMAm-Lac(2)) micelles in order to overcome these drawbacks.
      It was shown that xanthone could be loaded in these micelles up to 2 mg/mL with
      ~100% entrapment efficiency and ~20% loading capacity. The average particle
      diameter of the xanthone loaded mPEG-b-p(HPMAm-Lac(2)) micelles as determined by
      dynamic light scattering ranged from 84 to 112 nm. In vitro assays showed that
      xanthone in its free form as well as loaded in polymeric micelles had a high
      cytotoxicity towards both doxorubicin sensitive and, importantly, resistant
      cancer cells. On the other hand empty mPEG-b-p(HPMAm-Lac(2)) micelles did not
      show any cytotoxicity towards normal cells (PBMCs). Interestingly, the cytostatic
      effect of xanthone towards normal cells was masked when loaded in the micelles.
      The mechanism of cell growth inhibition by xanthone-loaded polymeric micelles was
      mediated through induction of apoptosis, as evidenced from a subdiploid peak of
      propidium iodide stained cells using flow cytometric analysis. From the results
      of this study it can be concluded that xanthone has potent anticancer activity
      not only on sensitive but also on doxorubicin resistant cancer cell lines. mPEG-b
      p(HPMAm-Lac(2)) micelles are therefore attractive delivery systems of xanthone
      for the treatment of cancer.

PMID- 22377216
TI  - Electrospun nanofibers of a phosphorylated polymer--a bioinspired approach for
      bone graft applications.
AB  - Biomaterials based on bioinspired mineralization are expected to offer
      osteoconductive and osteoinductive scaffolds for bone regeneration. An important
      role in the mediation of in vivo biomineralization process is played by highly
      anionic non-collagenous phosphoproteins (NCP) bound to the collagen matrix.
      Inspired by this fact, synthetic analogues of the NCPs like polyvinyl phosphonic
      acid which provide surface nucleation sites have been employed successfully for
      mineralization of hard tissues. In this study, electrospun nanofibrous scaffolds
      of partially phosphorylated polyvinyl alcohol (PPVA) are prepared and studied for
      matrix mineralization and maturation of human pre-osteoblasts like MG63 cells.
      Partial phosphorylation was found to affect many solution properties of PVA like
      increase in surface tension, conductivity and semi-crystalline intermolecular
      hydrogen bond formations narrowing down the electrospinning window for PPVA. In
      vitro mineralization under SBF treatment was uniform along the length of fibers
      on PPVA nanofibers. Further, MG63 cells showed increased adherence and
      proliferation on PPVA nanofibers and the expression of alkaline phosphatase
      activity and cell-matrix calcium levels were about two times higher than PVA
      nanofibers. The study established fabrication of electrospun nanofibers of a
      partially phosphorylated polymer, PVA resulting in improved osteoconduction and
      expression of early markers of osteoinduction in MG63 cells.

PMID- 22377217
TI  - Selenium nanoparticles inhibit the growth of HeLa and MDA-MB-231 cells through
      induction of S phase arrest.
AB  - In vitro antiproliferative effects of selenium nanoparticles (nanoSe(0), 10-40
      MUmol/L) on HeLa (human cervical carcinoma) cells and MDA-MB-231 (human breast
      carcinoma) cells were examined by optical microscopic inspection and MTT assay in
      the present study. The nanoSe(0) effectively inhibited the growth of MDA-MB-231
      cells and HeLa cells in a dose-dependent manner. The morphology analysis with
      atomic force microscope showed that the HeLa cells treated with 10 MUmol/L
      nanoSe(0) were rough and shrunken with truncated lamellipodia at terminal part of
      the cells. Flow cytometric analysis demonstrated that HeLa cells were arrested at
      S phase of the cell cycle after exposed to nanoSe(0) (10 MUmol/L). Taken
      together, our results suggested that nanoSe(0) may be more helpful in cancer
      chemoprevention as a potential anticancer drug.

PMID- 22377218
TI  - Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded
      polymeric nanoparticles for breast cancer.
AB  - Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino
      17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90
      (HSP90). Folate targeted polylactide-co-glycolide-polyethylene glycol-folic acid
      (PLGA-PEG-FA) nanoparticles containing 17-AAG were prepared and characterized.
      Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were
      determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded
      folate targeted nanoparticles was 238.67+/-3.52 nm, drug loading was 8.25+/-2.49%
      and about 80% of drug was released from the nanoparticles over 10 days. Cellular
      uptake studies showed much higher intracellular uptake of folate targeted
      nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed
      2 fold increase (P<0.05, n=3) in the cytotoxicity of folate targeted nanoparticle
      in comparison to free drug or nontargeted nanoparticles. Due to their targeting
      ability, nanometer size, high drug loading and controlled release behavior, 17
      AAG loaded PLGA-PEG-FA nanoparticles might be developed as a targeted delivery
      system for breast and other cancer treatment.

PMID- 22377219
TI  - Surface differentiation of ferritin and apoferritin with atomic force microscopic
      techniques.
AB  - In the study reported herein, we differentiated the structure of ferritin from
      that of its demetalated counterpart, apoferritin, using field-effect-based atomic
      force microscopic (AFM) techniques. When ferritin was subjected to conductive
      mode AFM analysis, the protein resembled a pancake with a diameter of 10 nm
      adsorbed on the indium-doped tin-oxide substrate with its fourfold channel
      perpendicular to the substrate, whereas a flat, empty cavity was revealed for
      apoferritin. We also attempted to verify the conformational difference with
      magnetic-mode AFM. However, the resulting phase images failed to differentiate
      the proteins due to interference from the fringe effect. Despite this, the
      ferritin analysis revealed a sound correlation between the surface conductivity
      profiles and the phase profiles. In contrast, apoferritin showed a chaotic
      relationship in this respect. These results not only suggest that the magnetic
      domain of ferritin is limited to the iron aggregate in the core, but also
      demonstrate that AFM is a useful tool for protein conformation analysis.

PMID- 22377220
TI  - Hepatitis E virus infection in HIV-infected persons.
AB  - To determine whether hepatitis E virus (HEV) is a cause of hepatitis among HIV
      infected persons, we evaluated 1985-2009 data for US military beneficiaries.
      Evidence of acute or prior HEV infection was detected for 7 (4%) and 5 (3%) of
      194 HIV-infected persons, respectively. HEV might be a cause of acute hepatitis
      among HIV-infected persons.

PMID- 22377225
TI  - Obstetric and neonatal outcome after surgical treatment of cervical dysplasia.
AB  - OBJECTIVES: Conization is the gold standard today for the management of severe
      cervical dysplasia. However, with the increasing delay until first pregnancy,
      obstetric follow-up of patients with a history of conization is a growing
      concern. STUDY DESIGN: Retrospective case-control study using data from the
      electronic database of a university hospital. We compared the obstetric and
      neonatal outcome of 106 pregnancies delivered after conization with the outcome
      of 212 pregnancies of patients with no history of conization. RESULTS: A
      significant reduction in the mean gestational age at delivery (38.23 +/- 2.51
      weeks vs. 39.15 +/- 1.56 weeks) was observed, together with a higher rate of
      premature rupture of the membrane (9.4% vs. 1.9%), premature onset of labor (9.4%
      vs. 2.4%), premature delivery (17% vs. 3.8%) and neonatal hospitalization (17.9%
      vs. 6.6%) in the group of patients with history of conization. Children born to
      women who had surgery had a significantly lower birth weight (3146.9 +/- 611 g
      vs. 3347.3 +/- 502 g) and size (49.1 +/- 2.6 cm vs. 50.0 cm +/- 2.2 cm) than
      those of the control group. Furthermore, these children were more frequently
      admitted in the neonatal intensive care unit (22.6% vs. 10.4%, p=0.004).
      CONCLUSIONS: Conization is an important risk factor for premature birth and women
      with a history of conization require cautious obstetric management during
      pregnancy. Anti-HPV vaccination and proactive surveillance of low-grade or
      moderate dysplasia, instead of immediate surgery, should be encouraged in young
      patients.

PMID- 22377226
TI  - Ruptured ectopic pregnancy 11 years after supracervical hysterectomy: a case
      report.

PMID- 22377227
TI  - Diameter of dominant leiomyoma is a possible determinant to predict coexistent
      endometriosis.
AB  - OBJECTIVE: To identify the frequency and assess risk factors for unexpected
      discovery of peritoneal endometriotic implants in patients who underwent
      myomectomy or hysterectomy for symptomatic uterine leiomyomas. STUDY DESIGN: We
      retrospectively collected medical records of 829 patients with symptomatic
      leiomyomas in The University of Tokyo Hospital. All the patients underwent
      abdominal or laparoscopic surgeries between January 2001 and December 2010 and
      the presence or absence of endometriosis during surgery was analyzed. Possible
      determinant to predict coexistent endometriosis was statistically investigated.
      RESULTS: In total, 105 leiomyoma cases (12.7% in 829 patients) were diagnosed
      with endometriosis. Patients with small dominant leiomyomas were significantly
      complicated by peritoneal endometriotic implants (small leiomyomas were
      classified as < 8 cm). The patients with both diagnoses were more likely to be
      infertile and at age 39 years or younger than those with leiomyoma alone.
      CONCLUSIONS: Women undergoing myomectomy or hysterectomy with both endometriosis
      and leiomyomas have several different clinical features compared with women with
      only leiomyomas. The size of largest leiomyoma may provide an important clue for
      coexistent endometriosis. Women with substantial infertility despite a smaller
      leiomyomas burden may be more likely to have a surgical indication for
      concomitant endometriosis.

PMID- 22377228
TI  - Theories of urinary incontinence causation: aetiological descriptions by sub
      Saharan African women.
AB  - OBJECTIVE: To describe the perceived causes of urinary incontinence (UI) and
      factors associated with awareness of causes of UI among women in the community.
      STUDY DESIGN: Secondary analysis of data extracted from the Ibadan Urinary
      Incontinence Household Survey (IUIHS), a multi-stage community survey conducted
      among 5001 women in Nigeria. RESULTS: The mean age was 34.8 years (SD=14.2). The
      majority had at least secondary education and were currently married. Within this
      population, 13% had ever leaked urine. On their perception of possible
      aetiological factors of UI, 20.5% mentioned pelvic floor or bladder-related
      causes such as stress incontinence triggers and bladder problems; 14.6% mentioned
      uncontrollable factors such as medical comorbidity, age and prior surgery; 8.8%
      attributed the cause to being female; and 6.8% mentioned sex-related factors.
      Multiple logistic regression analysis revealed significantly lower odds of
      awareness of the aetiology of urinary incontinence among women aged less than 30
      years, those with lower level of education, rural women, those with five or more
      children and women without history of urine leakage. CONCLUSIONS: The study shows
      a low level of awareness of possible cause of UI amongst women surveyed. We
      recommend health education and mobilization of women on the right aetiological
      factors of UI.

PMID- 22377229
TI  - Prevalence of premenstrual syndrome and premenstrual dysphoric disorder in a
      population-based sample in China.
AB  - OBJECTIVE: To investigate the prevalence of premenstrual syndrome (PMS) and
      premenstrual dysphoric disorder (PMDD), and the frequency and severity of the
      symptoms in a population-based sample of Chinese women of reproductive age. STUDY
      DESIGN: Women aged 18-45 years were screened for suspected PMS and PMDD based on
      the ACOG recommendations for a diagnosis of PMS and diagnostic and statistical
      manual of mental disorders, fourth edition (DSM-IV). For those who were
      consistent with PMS diagnostic criteria, the daily record of severity of problems
      (DRSP) questionnaire was used to assess the symptoms prospectively over 2 months.
      Participants were then categorized as having no perceived symptoms, mild PMS,
      moderate PMS, and PMDD, based on a validated algorithm. RESULTS: Among the study
      group, the incidence of PMDD was 2.1% and PMS was 21.1%. The most common symptoms
      were irritability (91.21%), breast tenderness (77.62%), depression (68.31%),
      abdominal bloating (63.70%) and angry outbursts (59.62%). CONCLUSION: The
      prevalence of PMS/PMDD and the frequency and severity of the symptoms have their
      own characteristics in Chinese women.

PMID- 22377231
TI  - Community-associated Clostridium difficile infections, Monroe County, New York,
      USA.
AB  - We conducted active sentinel surveillance in Monroe County, New York, USA, to
      compare incidence of community-associated Clostridium difficile infections (CA
      CDIs) with that of health care-associated infections (HA-CDIs) and identify
      exposure and strain type differences between CA and HA cases. Patients positive
      for C. difficile toxin and with no documented health care exposure in the
      previous 12 weeks were defined as possible CA case-patients. Patients with onset
      in a health care setting or recent health care exposure were defined as HA case
      patients. Eighteen percent of CDIs were CA; 76% were in persons who reported
      antimicrobial drug use in the 12 weeks before CDI diagnosis. Strain type
      distribution was similar between CA and HA cases; North American pulsed-field 1
      was the primary strain (31% CA, 42% HA; p = 0.34). CA-CDI is an emergent disease
      affecting patients recently exposed to antimicrobial drugs. Community strains are
      similar to those found in health care settings.

PMID- 22377232
TI  - Valsartan inhibited HIF-1alpha pathway and attenuated renal interstitial fibrosis
      in streptozotocin-diabetic rats.
AB  - AIM: To investigate the effect of angiotensin II AT1 receptor blocker valsartan
      on hypoxia-inducible factor (HIF)-1alpha-mediated gene activation and its
      association with renal interstitial fibrosis (RIF) in diabetic nephropathy rats.
      METHODS: Sprague-Dawley rats were randomly divided into 3 groups: control (C
      group), streptozocin-induced diabetic nephropathy (D group), and valsartan
      treated D rats (T group). At end of the 4th, 8th and 12th week 6 rats from each
      group were sacrificed and blood, urine and kidneys were collected. Blood glucose,
      serum creatinine (Scr) and 24-h urinary protein were measured and kidneys were
      processed for Masson-stain as well as immunohistochemistry and real time-PCR
      analyses of the expressions of HIF-1alpha, and its target genes tissue inhibitor
      of metalloproteinase (TIMP)-1 and endothelin (ET)-1 in the kidney. RESULT: (1) At
      the 4th, 8th and 12th week, the areas of RIF were significantly increased in D
      and T groups, which was accompanied by higher levels of 24-h urinary protein,
      Scr, HIF-1alpha, ET-1 and TIMP-1 compared with C group. (2) At the 8th and 12th
      week, the above changes were significantly attenuated in T group compared with D
      group. CONCLUSIONS: Valsartan may reduce HIF-1alpha-mediated gene activation and
      consequently improve kidney damage in diabetic nephropathy rats.

PMID- 22377233
TI  - Disabling chronic low back pain with Modic type 1 MRI signal: acute reduction in
      pain with intradiscal corticotherapy.
AB  - OBJECTIVES: The objective of the current study was to compare short- and long
      term effect on chronic low back pain of intradiscal injection of
      methylprednisolone with or without presence of Modic type 1 MRI changes. PATIENTS
      AND METHODS: Medical charts of patients receiving intradiscal injection of
      methylprednisolone from January 1, 1995 to December 31, 1998 were retrospectively
      reviewed. Clinical parameters were recorded at baseline, 24h after injection and
      at follow-up (12-14 months). Patients were studied in three groups: Modic I-a, if
      patients had Modic type 1 changes with no previous surgery or nucleolysis (n=30);
      Modic I-b, if patients had Modic type 1 changes at the level of previous surgery
      or nucleolysis (n=37); Control, if patients had no Modic type 1 changes (n=30).
      RESULTS: Twenty-four hours after methylprednisolone injection, higher proportion
      of patients with self-assessed improvement was observed in Modic I-a (90%) and
      Modic I-b (71%) than in Control (30%). Low back pain decreased in both Modic
      groups. Low back pain did not vary from baseline in controls. No effect was
      detected in three groups, neither for radiating pain 24h after injection, nor for
      any outcome parameters at the latest follow-up. CONCLUSIONS: We suggest that
      patients with disabling chronic low back pain and Modic type 1 MRI changes have
      specific acute response to intradiscal injection of methylprednisolone. Clinical
      studies are however necessary to further investigate the effectiveness and safety
      of such injections.

PMID- 22377238
TI  - Triaging TIA/minor stroke patients using the ABCD2 score does not predict those
      with significant carotid disease.
AB  - BACKGROUND: 'Rapid Access' TIA Clinics use the ABCD(2) score to triage patients
      as it is not possible to see everyone with a suspected TIA <24 h. Those scoring 0
      3 are seen within seven days, while patients scoring 4-7 are seen as soon as
      possible (preferably <24 h). It was hypothesized that patients scoring 4-7 would
      have a higher yield of significant carotid disease. METHODS: Prospective study of
      correlation between Family Doctor (FD) or Emergency Department (ED) ABCD(2) score
      and specialist consultant Stroke Physician measured ABCD(2) score and prevalence
      of >=50% ipsilateral carotid stenosis or occlusion in patients presenting with
      'any territory' TIA/minor stroke or 'carotid territory' TIA/minor stroke.
      RESULTS: Between 1.10.2008 and 31.04.2011, 2452 patients were referred to the
      Leicester Rapid Access TIA Service. After Stroke Physician review, 1273 (52%)
      were thought to have suffered a minor stroke/TIA. Of these, both FD/ED referrer
      and Specialist Stroke Consultant ABCD(2) scores and carotid Duplex ultrasound
      studies were available for 843 (66%). The yield for identifying a >=50% stenosis
      or carotid occlusion was 109/843 (12.9%) in patients with 'any territory'
      TIA/minor stroke and 101/740 (13.6%) in those with a clinical diagnosis of
      'carotid territory' TIA/minor stroke. There was no association between ABCD(2)
      score and the likelihood of encountering significant carotid disease and analyses
      of the area under the receiver operating characteristic curve (AUC) for FD/ED
      referrer and stroke specialist ABCD(2) scores showed no prediction of carotid
      stenosis (FD/ED: AUC 0.50 (95%CI 0.44-0.55, p = 0.9), Specialist: AUC 0.51 (95%CI
      0.45-0.57, p = 0.78). CONCLUSIONS: The ABCD(2) score was unable to identify
      TIA/minor stroke patients with a higher prevalence of clinically important
      ipsilateral carotid disease.

PMID- 22377234
TI  - Fluid management and risk factors for renal dysfunction in patients with severe
      sepsis and/or septic shock.
AB  - INTRODUCTION: The causative role of new hydroxyethyl starch (HES 130/0.4) in
      renal dysfunction frequency (a > 50% increase in serum creatinine or need for
      renal replacement therapy (RRT)) remains debated. Using the database of a
      multicenter study focusing on patients with severe sepsis and septic shock, the
      present study aimed at identifying factors associated with the occurrence of
      renal dysfunction. METHODS: Among the 435 patients in a multicenter study of
      patients with severe sepsis and septic shock in 15 Southern French ICUs, 388
      patients surviving after 24 hour, without a history of renal failure were
      included. Factors associated with renal dysfunction and RRT were isolated using a
      multivariate analysis with logistic regression. RESULTS: Renal dysfunction was
      reported in 117 (33%) patients. Ninety patients required RRT. Among study
      participants, 379 (98%) were administered fluids in the first 24 hours of
      management: HES 130/0.4 only (n=39), crystalloids only (n=63), or both HES
      130/0.4 and crystalloids (n=276). RRT was independently associated with the need
      for vasopressors and the baseline value of serum creatinine in the first 24
      hours. Multivariate analysis indicated that male gender, SAPS II score, being a
      surgical patient, lack of decrease in SOFA score during the first 24 hours, and
      the interventional period of the study were independently associated with renal
      dysfunction. Mortality increased in the presence of renal dysfunction (48% versus
      24%, P<0.01). CONCLUSIONS: Despite being used in more than 80% of patients with
      severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first
      24 hours of management was not associated with the occurrence of renal
      dysfunction.

PMID- 22377240
TI  - Food label use and food label skills among immigrants from the former Soviet
      Union.
AB  - OBJECTIVE: To assess food label use and skills and to identify their correlates
      among immigrants from the former Soviet Union (FSU). DESIGN/SETTING/PARTICIPANTS:
      Cross-sectional survey of a convenience sample of 200 FSU immigrants residing in
      New York City. VARIABLES MEASURED: Food label use and skills; acculturation; and
      socioeconomic and psychosocial factors. ANALYSIS: Chi-square tests and
      multivariate logistic regression analysis assessed relationships among the
      outcomes and socioeconomic and other characteristics. RESULTS: Fifty-five percent
      reported using food labels always/often; only 32% had good label skills. FSU
      immigrants particularly had difficulty understanding servings per package and
      percent daily value. Food label use was significantly associated with factors
      such as positive attitude toward food labels, and importance of recommendations
      such as avoiding too much salt and saturated fat. However, these factors were not
      related to food label skills, which was positively associated with longer
      residency in the United States (> 7 y). CONCLUSIONS AND IMPLICATIONS: There is a
      need for nutrition education among FSU immigrants to increase their food label
      use and skills to promote healthful food selection. Developers of new food labels
      should consider ways to present percent daily value and servings per package in a
      more consumer-friendly manner. Simplifying the presentation of this information
      could improve food label skills in FSU immigrants, among others.

PMID- 22377242
TI  - Adenovirus-associated deaths in US military during postvaccination period, 1999
      2010.
AB  - Adenoviruses are frequent causes of respiratory disease in the US military
      population. A successful immunization program against adenovirus types 4 and 7
      was terminated in 1999. Review of records in the Mortality Surveillance Division,
      Armed Forces Medical Examiner System, identified 8 deaths attributed to
      adenovirus infections in service members during 1999-2010.

PMID- 22377245
TI  - [Neonatal exposure to active pulmonary tuberculosis in a maternity ward:
      screening and clinical course of a cohort of exposed infants].
AB  - Few data are available on the impact of a tuberculosis exposure on newborns in a
      maternity ward. OBJECTIVES: To describe the screening and clinical course of
      infants exposed during the neonatal period to a caregiver with bacillary
      tuberculosis. PATIENTS AND METHODS: Infants exposed during the postnatal period
      in a maternity unit in Paris, from March to August 2005, to a caregiver with
      bacillary tuberculosis were included in a standardized screening protocol. The
      screening performed at baseline (M0) and at 3 months (M3) included a clinical
      evaluation, a tuberculin skin test (TST), and a chest X-ray. A preventive
      treatment for tuberculosis with isoniazid and rifampicin for 3 months was
      systematically proposed. RESULTS: At M0, 182 of the 217 infants (84%) with
      significant exposure were evaluated. Data were available for 172 infants. The
      median age at M0 was 4.9 months (IQR=3.8-6.2). At M0, 4 of 172 infants (2.3%) had
      latent TB infection. Between M0 and M3, 19 infants (11%) were lost to follow-up
      and 1 on 153 developed a latent TB infection. No cases of tuberculosis disease
      were diagnosed. The treatment was administered properly in 83% of cases and side
      effects were observed in 11% of infants without any serious adverse event. Four
      infants received no treatment and 11 stopped their treatment prematurely.
      CONCLUSION: In the absence of neonatal massive exposure, although low (2.9%), the
      risk of latent TB infection requires close monitoring of the infants exposed.
      However, in the context of a mild exposure in the maternity unit, surveillance
      without systematic initiation of TB preventive treatment could be discussed.

PMID- 22377246
TI  - [Influence of hospital location on short-term fate of premature infants born at
      34 weeks of gestation].
AB  - In France, new care units have emerged in maternity wards for the treatment of
      moderate prematurity, called mother-child units (MCU). We compared the length of
      hospitalization between the MCUs and the neonatal units (NNUs) for premature
      infants born at 34 weeks of amenorrhea at Grenoble university hospital. This was
      a retrospective, single-center study, including 99 premature infants born from 34
      of amenorrhea to 34 weeks+6 days between 2004 and 2009. Were included all
      premature 34-week infants hospitalized in the NNU or the MCU excluding those with
      respiratory distress, birth defects, and including infants whose birth weight was
      less than 1500g admitted to the neonatal intensive care unit or transferred
      secondarily to the MCU. The characteristics of both groups were similar apart
      from a lower birth weight in the NNU group (1892 vs. 2182g) and gestational age
      less than in the NNU group (34.1 vs. 34.3 SA). Our primary outcome, length of
      hospital stay, was significantly shorter in the MCU (15.4 vs. 20.7 days in the
      NNU, P<0.01) as well as the duration of nasogastric tube feeding (2.8 vs. 9.1
      days, P<0.01). This difference remained after adjustment for birth weight and
      gestational age. Our retrospective study shows that the length of hospitalization
      of premature infants born at 34 weeks gestation and hospitalized in our center is
      significantly shorter when they are admitted to the MCU rather than neonatology.
      For this reason, this mode of hospitalization in maternity MCUs can be
      recommended.

PMID- 22377248
TI  - Is the sodium level per se related to mortality in hospitalized patients with
      severe hyponatremia?
AB  - INTRODUCTION: Severe hyponatremia is a serious medical condition that is
      associated with morbidity and mortality. Controversy still exists regarding the
      prevalence, cause and mortality of hyponatremia. PATIENTS AND METHODS: Of the
      hyponatremic patients, we studied 116 severe hyponatremic patients. Severe
      hyponatremia was defined as a serum sodium concentration equal to or less than
      120 mmol/l at least twice. RESULTS: The mean age of the patients was 67.3 +/-
      14.9 years. The mean sodium level at the time of diagnosis was 114.9 +/- 5.2
      mmol/l. Normal extracelluar fluid volume (ECFV) was reported in 44 patients
      (37.9%). 24 (20.7%) of 44 patients were diagnosed with the syndrome of
      inappropriate antidiuretic hormone secretion (SIADH). Excess ECFV and depleted
      ECFV were reported in 37 (31.9%) and 18 patients (15.5%), respectively. In 17
      patients (14.7%), the exact causes could not be determined due to incomplete
      laboratory studies. On the univariate analysis, age (p = 0.030), the Charlson's
      risk index (p = 0.000) and the correction rate (p = 0.000) were associated with
      the 1-year survival. The time of onset (p = 0.051) and the initial serum sodium
      level (p = 0.986) were not associated with the 1-year survival. On the
      multivariate analysis, the Charlson's risk index (p = 0.003) and the correction
      rate (p = 0.033) were independently associated with 1-year survival. CONCLUSION:
      This study showed that the sodium level per se is not related to mortality, but a
      higher Charlson's risk index and a slow rate of correcting the sodium are related
      with mortality. For improving the survival of patients with severe hyponatremia,
      we should pay more attention to correct the underlying comorbidity.

PMID- 22377247
TI  - Role of oxidative stress in cardiovascular effects of anemia treatment with
      erythropoietin in predialysis patients with chronic kidney disease.
AB  - BACKGROUND/AIM: Oxidative stress (OS) is involved in left ventricular hypertrophy
      (LVH). Short-term treatment with erythropoietin (EPO) in chronic kidney disease
      (CKD) complicated by anemia and LVH is associated with a reduction in left
      ventricular mass (LVM). We proposed to assess whether the pro-oxidant status of
      CKD influences these outcomes. METHODS: Predialysis patients (n = 76) with CKD
      and hemoglobin (Hb) levels < 11 g/dl received EPO for 6 months. The effects of
      this anemia correction on LVH regression were evaluated using echocardiography.
      Patients with LVM decrease > 10% were considered "responders" (n = 25) to
      treatment and those with LVM change < 10% were considered "non-responders" (n =
      24). Measurement of OS included plasma and erythrocyte oxidized (GSSG) and
      reduced (GSH) glutathione, GSH redox ratio (GSSG/GSH), erythrocyte glutathione
      peroxidase (GPx) and oxidized LDL (Ox- LDL). RESULTS: 49 patients completed the
      study. With EPO therapy, mean Hb levels increased from 9.9 +/- 0.6 to 12.8 +/-
      1.5 g/ dl (p < 0.0001) and LVM index decreased from 69.2 +/- 17.7 to 64.1 +/-
      19.6 g/m2.7 (p = 0.01). At 6 months, "non-responders" had higher systolic blood
      pressure, pulse pressure, GSSG and GSH redox ratio and lower GSH than
      "responders". In multivariate analysis, and following adjustment for confounding
      variables, systolic blood pressure and GSH redox ratio independently predicted
      LVH regression. CONCLUSION: Blood pressure and plasma GSH redox ratio (a marker
      of OS) are important predictors of LVH regression in anemic predialysis patients
      treated with EPO.

PMID- 22377249
TI  - Pumping iron: revisiting risks, benefits and strategies in treatment of iron
      deficiency in end-stage renal disease.
AB  - Iron deficiency is a common cause of anemia in patients with end stage renal
      disease (ESRD). Intravenous iron administration, especially in those requiring
      treatment with erythropoiesis stimulating agents (ESA) is an essential component
      of the management of anemia in ESRD patients. Iron improves hemoglobin, reduces
      ESA dose requirement and also has nonerythropoietic effects including improvement
      in physical performance, cognition and amelioration of restless leg syndrome.
      However, iron can promote oxidative stress, cause endothelial dysfunction,
      inflammation and tissue injury, and has a potential to cause progression of both
      CKD and cardiovascular disease. In this review, we discuss the benefits and risks
      associated with i.v. iron and the practical aspects of iron administration that
      can minimize the complications related to iron therapy in ESRD.

PMID- 22377250
TI  - A study of the association of higher parathormone levels with health-related
      quality of life in hemodialysis patients.
AB  - Secondary hyperparathyroidism (SHPT) is associated with poor outcome including
      mortality, hospitalization, as well as greater healthcare resource utilization
      and costs in chronic kidney disease (CKD). We hypothesized that SHPT is also
      associated with poor self reported health-related quality of life (HRQOL) in
      prevalent hemodialysis (HD) patients. We conducted a case-control study in
      patients with CKD receiving longterm HD treatment, in six dialysis clinics in
      Greece. HRQOL was estimated with the KDQOL-SFTM questionnaire, version 1.3, which
      includes 43 kidney disease targeted items, and 36 items that provide a generic
      core and an overall health rating item, with a higher score reflecting a more
      favorable health state. A total of 156 completed the questionnaire, 50 with high
      parathormone levels (i.e., PTH > 300 pg/ml and or under vitamin D receptor
      activators, mean: 329 +/- 160.9 pg/ml) and 106 with low parathormone levels (PTH
      < 300 pg/ml, mean: 132.4 +/- 69.0 pg/ml) in a 2 : 1 randomization assignment.
      Patients with high and with low PTH were 62.1 +/- 14.9 and 65.9 +/- 14.2 y old
      and the median dialysis vintage time was 31 and 37 months, respectively. There
      were no significant differences regarding the presence of comorbidities between
      groups. Patients with high PTH, compared to patients with low PTH, had lower pain
      component summary (57.6 +/- 33.5 vs. 69.2 +/- 28.9; p = 0.041) and physical
      component summary (41.0 +/- 23.8 vs. 50.0 +/- 20.8; p = 0.031). Both pain
      component summary and physical component summary differences remained significant
      after adjustment for age, gender and vintage (p = 0.036 and p = 0.029,
      respectively). Low PTH patients scored better in 18 out of 23 subscales. In HD
      patients, SHPT appears to be associated with worse pain component summary score
      (p = 0.036) and physical component summary score (p = 0.029). Additional studies
      are needed to verify these associations and to examine whether correction of SHPT
      can improve HRQOL.

PMID- 22377251
TI  - Genitourinary abnormalities in an asymptomatic screening population: findings on
      virtual colonoscopy.
AB  - INTRODUCTION: The true incidences of genitourinary conditions in the modern era
      are not completely known. We sought to determine the incidence of genitourinary
      abnormalities in a group of asymptomatic adult patients undergoing axial imaging
      with virtual colonoscopy. METHODS: We performed a post-hoc analysis of imaging
      results from a prospective, IRB-approved study that randomized patients to
      screening "virtual" CT colonography (CTC) followed by standard endoscopic
      colonoscopy. CTC scans were reviewed separately by an independent radiologist and
      a urologist for genitourinary abnormalities. Genitourinary abnormalities were
      characterized as of minor, moderate, or major clinical significance. Identified
      nephroliths were categorized by location, laterality, size, and number. Student's
      t-tests and Fisher's exact-tests were used for continuous and categorical
      variables as appropriate. RESULTS: Of 490 patients undergoing CTC and eligible
      for analysis, no genitourinary abnormalities were found in 294 (60%), minor
      genitourinary abnormalities were found in 100 (20.4%), moderate genitourinary
      abnormalities were found in 86 (17.6%), and major genitourinary abnormalities
      were found in 10 (2%). Renal cysts (n = 60, 12%) were the most common minor
      urologic findings. Moderate and major genitourinary findings of nephrolithiasis,
      adrenal adenomas, and renal masses were noted in 13.9%, 3%, and 2% of the
      population, respectively. The largest stone was 1.2 cm, and the smallest was 1
      mm; while 59% had stones < 3mm, 20% between 3 mm and 5 mm, 18% between 5 mm and
      10 mm, and 3% > 10 mm in size. Unilateral stones were found in 85%, while
      bilateral were found in 15%, and the average number of stones was 2, (range 1 -
      16). Age and male sex were significantly associated with moderate or major
      genitourinary findings p = 0.04 and p = 0.05, respectively. CONCLUSIONS: CT
      colonography in an asymptomatic screening population helped to identify
      nephrolithiasis in 13.9%. Moderate and major urologic abnormalities were found in
      20% of the cohort. Risk factors included male sex and older age.

PMID- 22377252
TI  - Association between anti-C1q antibodies and glomerular tuft necrosis in lupus
      nephritis.
AB  - BACKGROUND: Proliferative glomerulonephritis includes various glomerular lesions
      in patients with systemic lupus erythematosus (SLE) that might have distinct
      pathogenic mechanisms. The aim of the study was to determine whether anti-C1q
      antibodies, which are associated with lupus nephritis, were specifically
      associated with given glomerular histopathological lesions. METHODS: The presence
      and titer of anti-C1q antibodies were determined in a retrospective study
      including 63 SLE patients with biopsy-proven lupus nephritis. RESULTS: We
      confirmed the correlation between the presence of anti-C1q antibodies with both
      clinical and immunological markers of disease activity. We showed that the
      presence of anti- C1q antibodies was significantly associated with glomerular
      tuft necrosis and crescents, major criteria of active lesions. Additionally, no
      necrosis was found in patients without anti- C1q antibodies, giving anti-C1q
      antibodies a 100% negative predictive value for glomerular tuft necrosis.
      Conversely, there was no difference in the percentage of glomeruli showing
      endocapillary proliferation or wire loops according to the anti-C1q status.
      CONCLUSION: Our data highlight for the first time an association of anti-C1q
      antibodies with necrotizing forms of lupus nephritis suggesting new insights into
      the pathogenesis and the treatment of this entity.

PMID- 22377254
TI  - Changes in renal function in long-term survivors of allogeneic hematopoietic stem
      cell transplantation: single-center experience.
AB  - BACKGROUND: Renal dysfunction after allogeneic hematopoietic stem cell
      transplantation (HSCT) has been increasingly reported. However, there are few
      reports on the changes of the estimated glomerular filtration rate (eGFR) in long
      term survivors after allogeneic HSCT. PATIENTS AND METHODS: The medical records
      at Seoul St. Mary's Hospital in Korea were reviewed to identify all adult (> 18
      years-of-age) patients who had undergone high-dose chemotherapy and allogeneic
      HSCT between January 2001 and December 2005. Among these patients, those with < 5
      years of follow-up and relapse within 5 years after HSCT were excluded. 85
      patients were enrolled. RESULTS: The mean follow-up was 76.0 +/- 13.5 months. The
      eGFR recorded 3 months after HSCT was significantly decreased compared with the
      eGFR recorded before HSCT. Subsequently, early decreased eGFR was maintained
      during the 60 months after HSCT. Multivariate analysis showed that acute kidney
      injury (AKI) during HSCT, hypertension (HTN) and eGFR before HSCT was differently
      associated with changes in eGFR. The eGFR in patients who had AKI decreased
      significantly at 3 months after HSCT. After 3 months, the eGFR recovered to reach
      a lower level than in patients without AKI. The level was maintained during the
      60 months after HSCT. The eGFR in patients who had low eGFR before HSCT (< 90
      ml/min) decreased significantly at 3 months after HSCT, which was also maintained
      during the 60 months after HSCT. The eGFR in patients who had HTN also decreased
      significantly at 3 months after HSCT. By contrast, the eGFR decreased
      consistently and slowly from 3 to 60 months. CONCLUSION: AKI and low baseline
      eGFR are associated with early renal dysfunction in patients after HSCT, but are
      not closely associated with long-term decline in eGFR. In contrast, eGFR in
      patients with HTN continuously decrease after 3 months of HSCT. Therefore, HTN
      seems to play a major role in the long-term decline in eGFR. These findings
      suggest that eGFR at 3 months after HSCT should be monitored closely for all
      patients who have undergone HSCT. Additionally, long-term follow-up of renal
      function is needed to prevent further renal damage for patients with HTN.

PMID- 22377253
TI  - Urine endothelin-1 levels as a predictor of renal scarring in children with
      urinary tract infections.
AB  - AIMS: Endothelin-1 (ET-1) contributes to renal fibrogenesis in several manners
      such as increasing collagen synthesis in mesangium, decreasing extracellular
      matrix (ECM) degradation by mesangial cells and stimulating mesangial
      contraction. The aim of our study was to investigate whether urine level of ET-1
      (uET-1) could represent a useful biomarker of renal scarring and if so, to
      determine the optimal cutoff level for uET-1 to predict a renal scar. METHODS: 44
      children with renal scarring and 32 children without renal scarring were enrolled
      in the study. Urine ET-1 was measured by enzyme-linked immunosorbent assay.
      RESULTS: Mean uET-1 level was significantly higher in the scar group than in
      controls (2.75 +/- 1.35 fmol/ml vs. 0.68 +/- 0.41 fmol/ml, p = 0.001). The
      optimal cut-off level was 1.064 fmol/ml for uET-1 to predict renal scarring.
      Using this cut-off point, sensitivity and specificity were 97.73% and 93.91%,
      respectively. AUC was found 0.975 (95% CI 0.917 - 0.996) for uET-1. Mean urine
      Endothelin-1/Creatinine ratio (uET-1/Cr) was also significantly higher in the
      scar group than in the control group (4.04 +/- 2.29 fmol/mg Cr vs. 1.09 +/- 0.67
      fmol/mg Cr, p = 0.0001). Using 1.67 fmol/mgCr as optimal cut-off level,
      sensitivity and specificity were 95.45% and 84.09%, respectively. AUC was 0.945
      (95% CI 0.875 - 0.982) for uET-1/Cr. CONCLUSION: Our study suggests that both uET
      1 and uET-1/Cr can be used for prediction of renal scarring in children with
      normal renal function. Measuring urine level of ET-1 can help us to avoid
      unnecessary DMSA studies if the patient's uET-1 level is found to be under the
      determined cut-off point.

PMID- 22377255
TI  - Pulmonary vascular calcification in a nocturnal hemodialysis patient.
AB  - Although vascular calcification in end-stage renal disease (ESRD) is common,
      metastatic pulmonary calcification (MPC) is an under-recognized complication of
      ESRD with the majority of individuals being asymptomatic. Similar to
      calcification in other arterial vascular beds, elevated serum calcium and
      phosphate appear to be potent risk factors although the exact pathogenesis of MPC
      remains largely unclear. Nocturnal hemodialysis (NHD) is a form of renal
      replacement therapy that offers superior control of serum phosphate and uremia
      compared to conventional (3 times weekly) intermittent hemodialysis and shows
      promise in delaying the progression of vascular calcification. Here, we report
      the first case of MPC involving the pulmonary vasculature in a patient treated
      with nocturnal hemodialysis and discuss the epidemiology, pathogenesis, histology
      and natural history of MPC.

PMID- 22377256
TI  - Retroperitoneal mass in a patient with Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is a necrotizing vasculitis that classically
      involves the upper and lower respiratory tracts and kidneys. Uncommonly, other
      sites may also be involved. We report on a patient previously diagnosed with and
      treated for WG who presented with flank pain and on further imaging was found to
      have a retroperitoneal mass. A surgical specimen of the tissue revealed multiple
      foci of necrotizing vasculitis. Consideration should be given to the possibility
      that mass-like lesions in patients with WG may not be tumors since the management
      and outcome differ from that of an active vasculitis.

PMID- 22377257
TI  - Disseminated kidney tuberculosis complicating autosomal dominant polycystic
      kidney disease: a case report.
AB  - Mycobacterium tuberculosis infection in patients with autosomal dominant
      polycystic kidney disease (ADPKD) is rare, and its diagnosis and treatment are
      difficult because numerous cysts are exposed to infection and antibiotics do not
      easily penetrate infected cysts. Here, we report the case of a 43-year-old
      Japanese man with disseminated urogenital tuberculosis (TB) and ADPKD without
      human immunodeficiency virus (HIV) infection. Delayed diagnosis and ineffective
      anti-TB chemotherapy worsened his condition. Finally, he underwent bilateral
      nephrectomy but experienced postoperative complications. In conclusion, kidney TB
      should be recognized as a cause of renal infection in ADPKD, and surgical
      treatment should be instituted without delay. The importance of early diagnosis
      and treatment cannot be overemphasized to prevent kidney TB deterioration.

PMID- 22377258
TI  - Proteasome inhibition with bortezomib: an effective therapy for severe antibody
      mediated rejection after renal transplantation.
AB  - Antibody-mediated rejection (AMR) following renal transplantation is  less
      responsive to conventional anti-rejection  therapies. Plasmapheresis (PP),
      intravenous  immunoglobulin (IVIg), rabbit antithymocyte  globulin (rATG) and
      rituximab deplete  immature B-cells but not mature plasma  cells. The proteasome
      inhibitor bortezomib  has activity against mature plasma cell, the  source of
      damaging donor-specific antibody  (DSA).We present the successful use of
      bortezomib  in 2 patients who developed AMR  following kidney transplantation.
      The first  patient was a 54-year-old white female who  received living-unrelated
      kidney transplantation  from her husband. She developed severe  AMR early after
      transplantation with rising  DSA titers consistent with an anamnestic  immune
      response by memory cells to the  donor antigens. Renal function deteriorated 
      despite treatment with pulse methylprednisolone  (MP), PP and IVIg. After
      initiation  of therapy with bortezomib, DSA titers became  negative and serum
      creatinine returned  to baseline with histological resolution of  AMR. The second
      patient was a 19-year-old  white male who received deceased donor  kidney
      transplantation and developed AMR  within 2 weeks, refractory to therapy with 
      pulse MP, PP and IVIg with rising DSA.  Bortezomib use resulted in disappearance
      of  DSA and renal function improvement. Both  patients tolerated the treatment
      well with  stable renal function at last follow-up. The  novel mechanisms of
      action and preliminary  results with bortezomib are encouraging, but  require
      larger studies and longer follow-up.

PMID- 22377259
TI  - Proliferative glomerulonephritis with monoclonal IgM deposits without
      Waldenstrom's macroglobulinemia: case report and review of the literature.
AB  - A 38-year-old man was presented with nephrotic syndrome associated with hematuria
      and mild hypocomplementemia. Renal biopsy revealed lobular mesangial
      proliferation, thickened capillary walls, and intraluminal protein thrombi.
      Immunofluorescence showed marked and mild depositions of immunoglobulin (Ig) M
      heavy chains and complement C3, respectively, in a peripheral lobular pattern. On
      light chain staining, only kappa (kappa) light and IgM heavy chains showed a
      similar pattern. Electron microscopy showed fine granular electrondense deposits
      in subendothelial areas and numerous globular deposits (varying size and density)
      in glomerular capillary lumens. Serum levels of Ig kappa, but not of free kappa,
      light chains were significantly increased. Bone marrow aspiration revealed a
      normocellular marrow. Waldenstrom's macroglobulinemia and cryoglobulinemia were
      ruled out. Clinically, steroid therapy was ineffective and proteinuria persisted.
      This report demonstrates that glomerular deposition of monoclonal IgM-kappa can
      produce membranoproliferative- like changes in the glomeruli. This condition may
      be recognized as proliferative glomerulonephritis with monoclonal IgM deposits
      similar to the recently recognized proliferative glomerulonephritis with
      monoclonal IgG deposits.

PMID- 22377260
TI  - ERP correlates of language-specific processing of auditory pitch feedback during
      self-vocalization.
AB  - The present study investigated whether the neural correlates for auditory
      feedback control of vocal pitch can be shaped by tone language experience. Event
      related potentials (P2/N1) were recorded from adult native speakers of Mandarin
      and Cantonese who heard their voice auditory feedback shifted in pitch by -50, 
      100, -200, or -500 cents when they sustained the vowel sound /u/. Cantonese
      speakers produced larger P2 amplitudes to -200 or -500 cents stimuli than
      Mandarin speakers, but this language effect failed to reach significance in the
      case of -50 or -100 cents. Moreover, Mandarin speakers produced shorter N1
      latencies over the left hemisphere than the right hemisphere, whereas Cantonese
      speakers did not. These findings demonstrate that neural processing of auditory
      pitch feedback in vocal motor control is subject to language-dependent neural
      plasticity, suggesting that cortical mechanisms of auditory-vocal integration can
      be shaped by tone language experience.

PMID- 22377261
TI  - Stimulus expectancy modulates inferior frontal gyrus and premotor cortex activity
      in auditory perception.
AB  - In studies on auditory speech perception, participants are often asked to perform
      active tasks, e.g. decide whether the perceived sound is a speech sound or not.
      However, information about the stimulus, inherent in such tasks, may induce
      expectations that cause altered activations not only in the auditory cortex, but
      also in frontal areas such as inferior frontal gyrus (IFG) and motor cortices,
      even in the absence of an explicit task. To investigate this, we applied spectral
      mixes of a flute sound and either vowels or specific music instrument sounds
      (e.g. trumpet) in an fMRI study, in combination with three different
      instructions. The instructions either revealed no information about stimulus
      features, or explicit information about either the music instrument or the vowel
      features. The results demonstrated that, besides an involvement of posterior
      temporal areas, stimulus expectancy modulated in particular a network comprising
      IFG and premotor cortices during this passive listening task.

PMID- 22377262
TI  - Neural correlates of temporal auditory processing in developmental dyslexia
      during German vowel length discrimination: an fMRI study.
AB  - This fMRI study investigated phonological vs. auditory temporal processing in
      developmental dyslexia by means of a German vowel length discrimination paradigm
      (Groth, Lachmann, Riecker, Muthmann, & Steinbrink, 2011). Behavioral and fMRI
      data were collected from dyslexics and controls while performing same-different
      judgments of vowel duration in two experimental conditions. In the temporal, but
      not in the phonological condition, hemodynamic brain activation was observed
      bilaterally within the anterior insular cortices in both groups and within the
      left inferior frontal gyrus (IFG) in controls, indicating that the left IFG and
      the anterior insular cortices are part of a neural network involved in temporal
      auditory processing. Group subtraction analyses did not demonstrate significant
      effects. However, in a subgroup analysis, participants performing low in the
      temporal condition (all dyslexic) showed decreased activation of the insular
      cortices and the left IFG, suggesting that this processing network might form the
      neural basis of temporal auditory processing deficits in dyslexia.

PMID- 22377264
TI  - Kinetics of aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase
      from rabbit skeletal muscle. Effect of agents possessing chaperone-like activity.
AB  - An aggregation test system based on the aggregation of UV-irradiated
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from rabbit skeletal muscle has
      been proposed. On the basis of the measurements of the enzyme activity and
      differential scanning calorimetry data a conclusion has been made that UV
      radiation results in formation of damaged protein molecules with lower
      thermostability. It was shown that the order of aggregation rate for UV
      irradiated GAPDH with respect to the protein was close to 2. This means that such
      a test system allows detecting the effect of various agents exclusively on the
      stage of aggregation of unfolded protein molecules. The influence of alpha
      crystallin and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on aggregation of
      UV-irradiated GAPDH was studied. Despite the fact that HP-beta-CD accelerates
      thermal aggregation of non-irradiated GAPDH, in the case of aggregation of UV
      irradiated GAPDH HP-beta-CD reveals a purely protective effect.

PMID- 22377270
TI  - All Your Base: a fast and accurate probabilistic approach to base calling.
AB  - The accuracy of base calls produced by Illumina sequencers is adversely affected
      by several processes, with laser cross-talk and cluster phasing being prominent.
      We introduce an explicit statistical model of the sequencing process that
      generalizes current models of phasing and cross-talk and forms the basis of a
      base calling method which improves on the best existing base callers, especially
      when comparing the number of error-free reads. The novel algorithms implemented
      in All Your Base (AYB) are comparable in speed to other competitive base-calling
      methods, do not require training data and are designed to be robust to gross
      errors, producing sensible results where other techniques struggle. AYB is
      available at http://www.ebi.ac.uk/goldman-srv/AYB/.

PMID- 22377271
TI  - Ocozocoautla de espinosa virus and hemorrhagic fever, Mexico.
AB  - Arenavirus RNA was isolated from Mexican deer mice (Peromyscus mexicanus)
      captured near the site of a 1967 epidemic of hemorrhagic fever in southern
      Mexico. Analyses of nucleotide and amino acid sequence data indicated that the
      deer mice were infected with a novel Tacaribe serocomplex virus (proposed name
      Ocozocoautla de Espinosa virus), which is phylogenetically closely related to
      Tacaribe serocomplex viruses that cause hemorrhagic fever in humans in South
      America.

PMID- 22377275
TI  - Wound closure of leg fasciotomy: comparison of vacuum-assisted closure versus
      shoelace technique. A randomised study.
AB  - BACKGROUND: Fasciotomies, though essential for the prevention and management of
      compartment syndromes, may increase morbidity and prolong hospitalisation. Two
      widely applied methods of delayed primary closure are compared in leg fasciotomy
      wounds. PATIENTS AND METHODS: Two groups, each of 25 patients with leg
      fasciotomies due to fractures and soft tissue injuries, who were randomly
      assigned to be treated either by vacuum assisted closure (VAC(r), n=42 wounds,
      group V) or by the shoelace technique (n=40 wounds, group S), were evaluated in
      this study. Wound length, time to definite closure, complications, need for
      additional interventions and daily treatment costs were data collected and
      statistically assessed. RESULTS: Wound closure time was significantly higher in
      group V compared to group S (p=0.001; 95% CI of the difference, 1.8-6.3 days).
      Five group V patients required split thickness skin grafts. In six group S
      patients, the vessel loops had to be replaced. The mean daily cost of negative
      pressure therapy alone was 135 euro (range 117-144 euro), whilst the mean daily
      cost of treatment for the shoelace technique was 14 euro ranging from 8 to 18
      euro (p=<0.001). CONCLUSIONS: Both VAC(r) and the shoelace technique are safe,
      reliable and effective methods for closure of leg fasciotomy wounds. VAC(r)
      requires longer time to definite wound closure and is far more expensive than the
      shoelace technique, especially when additional skin grafting is required.

PMID- 22377276
TI  - Does increased prehospital replacement volume lead to a poor clinical course and
      an increased mortality? A matched-pair analysis of 1896 patients of the Trauma
      Registry of the German Society for Trauma Surgery who were managed by an
      emergency doctor at the accident site.
AB  - INTRODUCTION: Severe bleeding after trauma frequently leads to a poor outcome.
      Prehospital fluid replacement therapy is regarded as an important primary
      treatment option. Our study aimed to assess the influence of prehospital fluid
      replacement therapy on the post-traumatic course of severely injured patients in
      a retrospective analysis of matched pairs. PATIENTS AND METHODS: The data of
      51,425 patients of the Trauma Registry of the German Society for Trauma Surgery
      were analysed. The following patients were included: Injury Severity Score >= 16
      points, primary admission, age >= 16 years, no isolated brain injury, transfusion
      of at least one unit of packed red blood cells (pRBC), systolic blood pressure >=
      60 mmHg at the accident site. The patients were divided into two groups according
      to the following matched-pair criteria (low-volume: 0-1500 ml prehospital volume
      replaced; high-volume: >= 1501 ml prehospital volume): intubation at the accident
      site (yes/no), time from injury to hospital +/- 10 min., means of rescue
      (emergency helicopter, MICU), Abbreviated Injury Scale (body regions), injury
      year, systolic blood pressure and age (years). All patients were managed by an
      emergency doctor at the accident site. RESULTS: A total of 948 patients in each
      group met the inclusion criteria. Increasing replacement volume was associated
      with an increased need for transfusion (pRBCs: low-volume: 7 units, high-volume:
      8.3 units; p<0.001) and a reduced ability to coagulate (prothrombin ratio (PR):
      low-volume: 68%, high-volume: 61.5%; p<0.001). Patients in shock (systolic BP<90
      mmHg) upon admission to the hospital were equally in both groups (25.6%; p=0.98).
      Significantly higher lethality was observed in cases of increasing volume (low
      volume: 22.7%, high-volume: 27.6%; p<0.01). CONCLUSIONS: Excessive prehospital
      fluid replacement leads to an increased mortality rate. The results of this study
      support the concept of restrained volume replacement in the prehospital treatment
      of patients with severe trauma.

PMID- 22377277
TI  - A multi-center survey of age of sexual debut and sexual behavior in Chinese
      women: suggestions for optimal age of human papillomavirus vaccination in China.
AB  - OBJECTIVE: Cervical cancer is the second most common cancer among women
      worldwide, and over 85% of cervical cancers occur in developing countries such as
      China. Lack of resources for nationwide cervical cancer screening in China makes
      vaccination against oncogenic strains of HPV particularly important. Knowledge of
      age at sexual debut and sexual behavior is essential prior to implementation of a
      national vaccination program. METHODS AND MATERIALS: A cross-sectional
      epidemiologic survey was conducted across 21 urban and rural sites in China to
      assess age at sexual debut and sexual behavior. 98.6% of the 11,852 recruited
      women aged 15-59 years were included in the analysis. Data were collected using a
      short, nurse-administered questionnaire and analyzed using standard descriptive
      statistics and survival analysis. RESULTS: In urban areas, more than ten percent
      of the 15-19 year old age group were already sexually active at the time of
      interview; this number increased to nearly 44% in the 20-24 year old age group.
      Chinese young women with an occupation were more likely to be sexually active
      compared to female students of the same age, irrespective of area of residence.
      The crude median sexual debut age for the youngest age group was 17 years,
      earlier than the sexual debut age reported by older cohorts. Younger age cohorts
      had an earlier menarche age than older cohorts and were more likely to have more
      sexual partners than older women, and more likely to have partners with more than
      one female partner. CONCLUSION: There is a trend towards earlier sexual debut and
      riskier sexual behaviors in younger age groups of Chinese women. These findings
      suggest that HPV vaccination of women between the ages of 13 and 15 years, before
      the completion of national compulsory education, is likely to contribute to the
      prevention of HPV infection and cervical cancer in China.

PMID- 22377278
TI  - Breast cancer among Yemeni women using the National Oncology Centre Registry 2004
      2010.
AB  - BACKGROUND: In developing countries including Arab countries breast cancer is one
      of the most common cancers found in women. Even though breast cancer incidence is
      lower in Arab developing countries than in western countries, Arabic women are
      more likely to be diagnosed at an earlier age than the women in western
      countries. METHOD: A descriptive study was undertaken to investigate the type of
      breast cancer, lymph node involvement, side of breast and, region and age
      distribution of breast cancer patients registered in the National Oncology Centre
      in Yemen. RESULTS: From September 2004 to December 2010, 2654 women across Yemen
      diagnosed with breast cancer were registered in the National Oncology Centre for
      treatment. Between the years 2004 and 2010, breast cancer represented 22% of all
      cancers registered in women. Seventy-one per cent of the women were aged 50 or
      younger at the time of diagnosis. The most common age group affected was women
      aged 41-50 years, with (35%) of cases occurring in this age. Invasive ductal
      carcinoma was the most common pathology (76%) and 79% of the patients had lymph
      node involvement at the time of diagnosis. Approximately 2% had bilateral disease
      and the frequency of left (44%) and right breast cancer (42%) were similar.
      CONCLUSION: This study has shown that breast cancer is a disease of young women
      in Yemen. The majority of women presented with lymph node involvement. Hence
      efforts are needed to increase breast cancer awareness in Yemen for early
      detection at all age groups, and to target women living in areas that have lower
      access to health care services.

PMID- 22377281
TI  - The survival and proliferation of fibroblasts on biocomposites containing
      genetically modified flax fibers: an in vitro study.
AB  - Natural fibers have long been used in several branches of industry. Nowadays,
      they are considered as composite materials in medicine with special focus on
      artificial tissue scaffolding, drug-release systems, cardiovascular patches and
      nerve cuffs. The purpose of this study has been to examine the in vitro
      biocompatibility of newly designed "green composites". Therefore, composites
      containing flax fibers from transgenic flax plants producing polyhydroxybutyrate
      (M50) and control (wt-NIKE) plants in a polylactid (PLA) or polycaprolactone
      (PCL) matrix were prepared and mice fibroblast viability and cytotoxicity
      determined after incubation for 12-48h and 3 weeks with those composites. After
      24h and 48h, all green composites have a strong influence on cell viability and
      membrane stability without any differences among each other. The cell viability
      of treated cells is approximately 82.5-93% of those of untreated control cells,
      respectively. The increase in cytotoxicity ranged between 1.4 and 2.9 fold
      compared to untreated cells. After 3 weeks of incubation, no significant changes
      were detectable in the amount of dead and living cells between composite treated
      and untreated cells. In conclusion, the tested new "green composites" showed a
      good biocompatibility. The biocompatibility of composites from transgenic flax
      plant fibers producing PHB did not differ from composites of non-transgenic flax
      plant fibers.

PMID- 22377282
TI  - Mannan-binding lectin deficiency - Good news, bad news, doesn't matter?
AB  - Mannan-binding lectin (MBL) deficiency has been classified as a commonly
      occurring immune disorder, affecting approximately 30% of the human population.
      MBL, being part of the innate immune system, supports the recognition of
      infectious pathogens by binding to carbohydrate moieties expressed on
      microorganisms and activates the lectin pathway of the complement system. MBL2
      gene polymorphisms are associated with quantitative and qualitative MBL
      abnormalities in the serum. The clinical impact of MBL deficiency and its
      association to a wide variety of diseases has been extensively studied. The
      picture is puzzling as the studies suggest a detrimental or beneficial or no
      impact of low or high MBL serum levels on disease susceptibility. In this review
      we attempt to extract what is relevant from the literature and address
      controversial issues. We finally suggest that a comprehensive understanding of
      the role of MBL in human diseases requires considering its context-dependency.

PMID- 22377283
TI  - Epsilonproteobacteria in humans, New Zealand.
AB  - Using PCR-denaturing gradient gel electrophoresis, we examined 49 fecal samples
      from healthy volunteers and 128 diarrhea specimens to assess the distribution of
      Epsilonproteobacteria that might be routinely overlooked. Our results suggest
      that certain taxa that are not routinely examined for could account for a
      proportion of diarrhea of previously unknown etiology.

PMID- 22377289
TI  - People with disabilities: the forgotten victims of violence.

PMID- 22377290
TI  - Prevalence and risk of violence against adults with disabilities: a systematic
      review and meta-analysis of observational studies.
AB  - BACKGROUND: About 15% of adults worldwide have a disability. These individuals
      are frequently reported to be at increased risk of violence, yet quantitative
      syntheses of studies of this issue are scarce. We aimed to quantify violence
      against adults with disabilities. METHODS: In this systematic review and meta
      analysis, we searched 12 electronic databases to identify primary research
      studies published between Jan 1, 1990, and Aug 17, 2010, reporting prevalence
      estimates of violence against adults (aged mainly >=18 years) with disabilities,
      or their risk of violence compared with non-disabled adults. We included only
      studies reporting violence occurring within the 12 months before the study. We
      assessed studies with six core quality criteria, and pooled data for analysis.
      FINDINGS: Of 10,663 references initially identified, 26 were eligible for
      inclusion, with data for 21,557 individuals with disabilities. 21 studies
      provided data suitable for meta-analysis of prevalence of violence, and ten for
      meta-analysis of risks of violence. Pooled prevalence of any (physical, sexual,
      or intimate partner) recent violence was 24.3% (95% CI 18.3-31.0) in people with
      mental illnesses, 6.1% (2.5-11.1) in those with intellectual impairments, and
      3.2% (2.5-4.1) in those with non-specific impairments. We identified substantial
      heterogeneity in most prevalence estimates (I(2) >75%). We noted large
      uncertainty around pooled risk estimates. Pooled crude odds ratios for the risk
      of violence in disabled compared with non-disabled individuals were 1.50 (95% CI
      1.09-2.05) for all studies combined, 1.31 (0.93-1.84) for people with non
      specific impairments, 1.60 (1.05-2.45) for people with intellectual impairments,
      and 3.86 (0.91-16.43) for those with mental illnesses. INTERPRETATION: Adults
      with disabilities are at a higher risk of violence than are non-disabled adults,
      and those with mental illnesses could be particularly vulnerable. However,
      available studies have methodological weaknesses and gaps exist in the types of
      disability and violence they address. Robust studies are absent for most regions
      of the world, particularly low-income and middle-income countries. FUNDING: WHO
      Department of Violence and Injury Prevention and Disability.

PMID- 22377291
TI  - [New generation sequencing in medical genetics].

PMID- 22377292
TI  - [Transendothelial migration through the neurovascular unit: "a cup to cross the
      barrier"].

PMID- 22377293
TI  - [Early gene expression dysregulation and intellectual disability].

PMID- 22377294
TI  - [Extreme microcephaly and growth retardation caused by mutations in a non-coding
      RNA component of the minor spliceosome].

PMID- 22377295
TI  - [Protecting vascular integrity in acute myocardial ischemia-reperfusion].

PMID- 22377296
TI  - [RIG-I: a viral RNA detector molecular switch].

PMID- 22377297
TI  - [An advanced model of a minimalistic synthetic cell].

PMID- 22377298
TI  - [Treatment of the respiratory distress syndrome in newborns: smoothened agonist
      counterbalances deleterious effects of glucocorticoids].

PMID- 22377299
TI  - [The mechanics of the cellular division or how to split a sphere into two?].

PMID- 22377300
TI  - [Medullary thymic epithelial cells expressing Aire, key mediators in the
      induction of T-cell tolerance].

PMID- 22377301
TI  - [First immortalised cell lines phenotypically and functionally equivalent to
      human insulin-secreting pancreatic beta cells].

PMID- 22377302
TI  - [Inositol phosphatase and bone mass: role of INPP4b].

PMID- 22377303
TI  - [Non thermal plasmas, a new strategy in oncology?].

PMID- 22377304
TI  - [Targeting malaria parasite at the level of apicoplast: an update].
AB  - In 1996, the discovery of a relic chloroplast in Plasmodium and Toxoplasma cells
      has strongly changed our vision of these parasites in the "Tree of Life", and has
      opened an unexpected new field of investigation in the search for antiparasitic
      treatments, including antimalarials. This review details our current
      understanding of the sophisticated evolution of the parasites of the Apicomplexa
      phylum and briefly covers a decade of research and development in drug discovery,
      trying to target the malaria parasite at the level of its plant-like organelle.
      Fifteen years after the discovery of the apicoplast and ten years after the
      publication of the genome of Plasmodium falciparum, it seems that we have
      completed a first phase of tests of available antibiotics and herbicides. In the
      human host, the liver phase is the only parasitic stage, for which biological
      functions harbored by the apicoplast, such as fatty acid biosynthesis, seem
      indispensable. During the erythrocytic phase, recent results have focused the
      attention on the processes controlling the biogenesis of the apicoplast, and one
      of the functions harbored by the apicoplast, i.e. the biosynthesis of
      isoprenoids, as major -promising targets for future treatments.

PMID- 22377305
TI  - [HIV controllers: how these patients control viral replication?].
AB  - Some patients infected by the HIV are called HIV controllers because viral
      replication remains undectectable during a prolonged period of time in the
      absence of any antiretroviral treatment. This state could be considered as a "
      functional cure " in these virally infected patients. Understanding mechanisms
      underlying this prolonged control of viral replication is key to the development
      of future vaccinal strategies. French ANRS is exploiting a cohort of HIV
      controllers since several years, and immunological analysis of these patients has
      yielded some mechanistic clues that this review will discuss. A striking feature
      is the very efficient and polyfunctional CD8 T cell response of these patients,
      which exhibits a high avidity against the gag protein of the virus. Other
      parameters and questions are studied : the role of HLA B57, overrepresented in
      this cohort ; how HIV controllers who do not express a very robust CD8 response
      control the viral replication ? The long term follow up of these patients will
      also give important informations on their -immunological, viral and clinical
      evolution.

PMID- 22377306
TI  - [Resistance acquisition via the bacterial SOS response: the inducive role of
      antibiotics].
AB  - After the euphoria of the antibiotic discovery and their tremendous action on
      bacterial infections outcomes, arrives a period of fear with the continuous
      emergence of bacteria that are resistant to almost all antibiotic treatments. It
      is becoming essential to better understand antibiotic resistance mechanisms to
      find new approaches to prevent the worldwide problem of multiresistance. The role
      of antibiotics on the direct induction of resistance acquisition is known. Recent
      studies have shown that some antibiotics, by inducing the bacterial SOS response,
      global repair response after DNA damages, are involved on a broader level in the
      induction, acquisition and dissemination of resistances in bacteria. We discuss
      here the role of antibiotics in resistance acquisition via the SOS response
      through several examples and the interest of identifying the SOS response
      regulators as the future targets of new families of antimicrobial molecules.

PMID- 22377307
TI  - [Sexual dimorphism in the XXI(st) century].
AB  - A new definition of sexual dimorphism is required. The divergent biology of the
      sexes is still largely ignored, overshadowed by sociocultural considerations and
      confined to its hormonal organizational and activational effects, while the genes
      unequally expressed by the sex chromosomes play an important role much earlier,
      after conception, to set the stage and throughout life. These different
      components have independent and parallel effects that can interact in a
      synergistic or antagonistic manner on differentiation and response processes to
      trigger or erase sex-specific differences. The epigenetic marks and machinery
      represent the perfect tools to keep the memory of which sex is ours from the very
      beginning of life. Within the context of the developmental origin of adult health
      and diseases (DOHaD), owing to their flexibility to the environment, epigenetic
      marks also represent a support to archive the effects of environments during
      development, according to the sex of the parent, in a sex-specific mode. In all
      tissues, including gonads and brain, different trajectories of genes and pathways
      are used at the basal levels and to modulate/dictate responses according to sex
      and gender. It is urgent to emphasize the need to take into consideration this
      new knowledge and to apply less sex-biased approaches in research, medicine and
      society, to enhance women health and well-being. A critical review and
      realization of gender-specific social constraints, an indeniably but slowly on
      going process, should allow us to "set free our sex biology" while detracting the
      delusion of hierarchy of the complex mechanisms involved.

PMID- 22377308
TI  - [Allele-specific therapy: suppression of nonsense mutations by readthrough
      inducers].
AB  - Ten percent of human hereditary diseases are linked to nonsense mutations
      (premature termination codon). These mutations lead to premature translation
      termination, trigger the synthesis of a truncated protein and possibly lead to
      mRNA degradation by the NMD pathway (nonsense mediated mRNA decay). For the past
      ten years, therapeutic strategies have emerged which attempt to use molecules
      that facilitate tRNA incorporation at premature stop codon (readthrough), thus
      allowing for the synthesis of a full length protein. Molecules currently used for
      this approach are mostly aminoglycoside antibiotics (gentamicin, amikacin...)
      that bind the decoding center of the ribosome. This therapeutic approach has been
      studied for various genetic diseases including Duchenne muscular dystrophy (DMD)
      and cystic fibrosis. The feasibility of this approach depends on induced
      readthrough level, mRNA quantity, re-expressed protein functionality and
      characteristics of each disease.

PMID- 22377309
TI  - [Misregulation of P-TEFb activity: pathological consequences].
AB  - P-TEFb stimulates transcription elongation by phosphorylating the carboxy
      terminal domain of RNA pol II and antagonizing the effects of negative elongation
      factors. Its cellular availability is controlled by an abundant non coding RNA,
      conserved through evolution, the 7SK RNA. Together with the HEXIM proteins, 7SK
      RNA associates with and sequesters a fraction of cellular P-TEFb into a
      catalytically inactive complex. Active and inactive forms of P-TEFb are kept in a
      functional and dynamic equilibrium tightly linked to the transcriptional
      requirement of the cell. Importantly, cardiac hypertrophy and development of
      various types of human malignancies have been associated with increased P-TEFb
      activity, consequence of a disruption of this regulatory equilibrium. In
      addition, the HIV-1 Tat protein also releases P-TEFb from the 7SK/HEXIM complex
      during viral infection to promote viral transcription and replication. Here, we
      review the roles played by the 7SK RNP in cancer development, cardiac hypertrophy
      and AIDS.

PMID- 22377310
TI  - [System biology and synthetic biology modify drug discovery and development].
AB  - Life Sciences are built on observations. Right now, a more systemic approach
      allowing to integrate the different organizational levels in Biology is emerging.
      Such an approach uses a set of technologies and strategies allowing to build
      models that appear to be more and more predictive (omics, bioinformatics,
      integrative biology, computational biology...). Those models accelerate the
      rational development of new therapies avoiding an engineering based only on
      trials and errors. This approach both holistic and predictive radically modifies
      the discovery and development modalities used today in health industries.
      Moreover, because of the apparition of new jobs at the interface of disciplines,
      of private and public sectors and of life sciences and engineering sciences, this
      implies to rethink the training programs in both their contents and their
      pedagogical tools.

PMID- 22377311
TI  - [The contribution of narrative ethics to healthcare].

PMID- 22377312
TI  - [Non-invasive prenatal paternity testing: a mixed blessing?].

PMID- 22377313
TI  - [Jumping translocations of chromosome 1q are recurring chromosomal -aberrations
      in neural derivatives of pluripotent stem cells].

PMID- 22377314
TI  - In vivo digestion of infant formula in piglets: protein digestion kinetics and
      release of bioactive peptides.
AB  - The first months of life correspond to a key period in human life where dramatic
      physiological changes (establishment of microbiota, development of the immune
      system, etc.) occur. In order to better control these changes it is necessary to
      understand the behaviour of food in the gastrointestinal tract of the newborn.
      Infant formula is the only food for the newborn when breast-feeding is
      impossible. The kinetics of digestion of milk proteins and the nature of the
      peptides liberated in the small intestine throughout infant formula digestion
      have never been extensively investigated so far and were therefore studied using
      the piglet as a model of the newborn child. Piglets were fed infant formula by an
      automatic delivery system during 28 d, and slaughtered 30, 90 and 210 min after
      the last meal. Contents of stomach, proximal and median jejunum and ileum were
      collected and characterised. The extent of beta-lactoglobulin (beta-lg), alpha
      lactalbumin (alpha-la) and casein proteolysis was monitored by inhibition ELISA,
      SDS-PAGE, immunoblotting and MS. At 30 min after the last meal, caseins were
      shown to be extensively hydrolysed in the stomach. Nevertheless, peptides
      originating mainly from beta-caseins (from 509 to 2510 Da) were identified in the
      jejunum and ileum of the piglets. beta-Lg partially resisted gastric digestion
      but completely disappeared in the stomach after 210 min. alpha-La had a similar
      behaviour to that of beta-lg. Two large peptides (4276 and 2674 Da) generated
      from beta-lg were present in the ileum after 30 and 210 min and only one (2674
      Da) after 90 min.

PMID- 22377319
TI  - Chromatin structural changes around satellite repeats on the female sex
      chromosome in Schistosoma mansoni and their possible role in sex chromosome
      emergence.
AB  - BACKGROUND: In the leuphotrochozoan parasitic platyhelminth Schistosoma mansoni,
      male individuals are homogametic (ZZ) whereas females are heterogametic (ZW). To
      elucidate the mechanisms that led to the emergence of sex chromosomes, we
      compared the genomic sequence and the chromatin structure of male and female
      individuals. As for many eukaryotes, the lower estimate for the repeat content is
      40%, with an unknown proportion of domesticated repeats. We used massive
      sequencing to de novo assemble all repeats, and identify unambiguously Z
      specific, W-specific and pseudoautosomal regions of the S. mansoni sex
      chromosomes. RESULTS: We show that 70 to 90% of S. mansoni W and Z are
      pseudoautosomal. No female-specific gene could be identified. Instead, the W
      specific region is composed almost entirely of 36 satellite repeat families, of
      which 33 were previously unknown. Transcription and chromatin status of female
      specific repeats are stage-specific: for those repeats that are transcribed,
      transcription is restricted to the larval stages lacking sexual dimorphism. In
      contrast, in the sexually dimorphic adult stage of the life cycle, no
      transcription occurs. In addition, the euchromatic character of histone
      modifications around the W-specific repeats decreases during the life cycle.
      Recombination repression occurs in this region even if homologous sequences are
      present on both the Z and W chromosomes. CONCLUSION: Our study provides for the
      first time evidence for the hypothesis that, at least in organisms with a ZW type
      of sex chromosomes, repeat-induced chromatin structure changes could indeed be
      the initial event in sex chromosome emergence.

PMID- 22377322
TI  - Promoter analyses and transcriptional profiling of eggplant polyphenol oxidase 1
      gene (SmePPO1) reveal differential response to exogenous methyl jasmonate and
      salicylic acid.
AB  - The transcriptional regulation of multigenic eggplant (Solanum melongena)
      polyphenol oxidase genes (SmePPO) is orchestrated by their corresponding
      promoters which mediate developmentally regulated expression in response to
      myriad biotic and abiotic factors. However, information on structural features of
      SmePPO promoters and modulation of their expression by plant defense signals are
      lacking. In the present study, SmePPOPROMOTERs were cloned by genome walking, and
      their transcription start sites (TSS) were determined by RLM-RACE. Extensive
      sequence analyses revealed the presence of evolutionarily conserved and over
      represented putative cis-acting elements involved in light-regulated
      transcription, biosynthetic pathways (phenylpropanoid/flavonoid), hormone
      signaling (abscisic acid, gibberellic acid, jasmonate and salicylate), elicitor
      and stress responses (cold/dehydration responses), sugar metabolism and plant
      defense signaling (W-BOX/WRKY) that are common to SmePPOPROMOTER1 and 2. The TSS
      for SmePPO genes are located 9-15bp upstream of ATG with variable lengths of 5'
      untranslated regions. Transcriptional profiling of SmePPOs in eggplant seedlings
      has indicated differential response to methyl jasmonate (MeJA) or salicylic acid
      (SA) treatment. In planta, while MeJA elicited expression of all the six SmePPOs,
      SA was only able to induce the expression of SmePPO4-6. Interestingly, in dual
      treatment, SA considerably repressed the MeJA-induced expression of SmePPOs.
      Functional dissection of SmePPOPROMOTER1 by deletion analyses using Agrobacterium
      mediated transient expression in tobacco leaves has shown that MeJA enhances the
      SmePPOPROMOTER1-beta-glucuronidase (GUS) expression in vivo, while SA does not.
      Histochemical and quantitative GUS assays have also indicated the negative effect
      of SA on MeJA-induced expression of SmePPOPROMOTER1. By combining in silico
      analyses, transcriptional profiling and expression of SmePPOPROMOTER1-GUS
      fusions, the role of SA on the modulation of MeJA-induced SmePPO1 expression has
      been elucidated. It is concluded that similar to the coding regions of multigenic
      SmePPOs, the regulatory elements are also evolutionarily conserved and fall into
      two distinct sub-classes based on their responses to MeJA and SA.

PMID- 22377324
TI  - The use of sodium hyaluronate-carboxymethylcellulose to prevent postoperative
      mastication pain from harvesting of temporalis fascia.
AB  - OBJECTIVE: To evaluate the anti-adhesive and anti-inflammatory effects of sodium
      hyaluronate-carboxymethylcellulose (HA-CMC) in reducing postoperative pain after
      temporalis fascia harvest during tympanomastoid surgery. MATERIALS AND METHODS:
      Between January and December 2009, 27 patients underwent tympanoplasty and open
      cavity mastoidectomy involving the harvesting of temporalis fasciae (more than
      3*4cm). At the end of surgery, patients were injected with 1.5g HA-CMC or normal
      saline around the fascia harvest area. Beginning immediately postoperatively and
      for 2 months after surgery, patients scored their pain in the temporal area on a
      visual analogue scale (VAS). RESULTS: There were no significant postoperative
      complications, such as bleeding or hematoma, in either control group. VAS scores
      of both groups decreased over time and were negligible after 2 months. VAS scores
      of the HA-CMC and control groups differed significantly (p<0.001 by repeated
      measures ANOVA for all VAS scores). CONCLUSION: HA-CMC can decrease immediate
      postoperative pain arising from tissue adhesion and inflammation, thus reducing
      postoperative mastication pain.

PMID- 22377321
TI  - Causes of pneumonia epizootics among bighorn sheep, Western United States, 2008
      2010.
AB  - Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain
      etiology. To help clarify the etiology, we used culture and culture-independent
      methods to compare the prevalence of the bacterial respiratory pathogens
      Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and
      Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected
      by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent
      detected at significantly higher prevalence in animals from outbreaks (95%) than
      in animals from unaffected healthy populations (0%), was the most consistently
      detected agent and the only agent that exhibited single strain types within each
      outbreak. The other respiratory pathogens were frequently but inconsistently
      detected, as were several obligate anaerobic bacterial species, all of which
      might represent secondary or opportunistic infections that could contribute to
      disease severity. These data provide evidence that M. ovipneumoniae plays a
      primary role in the etiology of epizootic pneumonia of bighorn sheep.

PMID- 22377325
TI  - The inhibition of Th17 immune response in vitro and in vivo by the carbosilane
      dendrimer 2G-NN16.
AB  - We evaluated the 2G-NN16-carbosilane dendrimer activities in Th17 response as a
      potential therapy for Th17 deregulated pathologies. IL17A, IL17F, IL22, IL23 and
      other interleukins secreted by Th17 cells CD4+ cells were down regulated when
      cells were cultured in the presence of this dendrimer. Furthermore, IL17F and
      IL17A protein levels in splenocytes from mice pretreated with 2G-NN16 dendrimer
      in a Th17 induction mouse model were lower than those corresponding to PBS
      treated mice. Treatment of mice with 2G-NN16 inhibited the Th17 response causing
      much more pathogenicity as indicated by the increase in the number of Candida
      albicans colonies in the kidneys as compared to PBS-treated mice. All these
      results suggest a potential pharmacological application for this dendrimer in the
      therapy of Th17-mediated diseases.

PMID- 22377326
TI  - Nonculture diagnostic tests for enteric diseases.
AB  - The diagnosis of acute gastroenteritis (AGE) has traditionally been based on
      culture results of feces from patients with diarrhea. Virtually everything we
      know about disease and the epidemiology of enteric pathogens, such as Salmonella
      spp., Shiga toxin-producing Escherichia coli (STEC), e.g., O157, and
      Campylobacter spp., has been generated from the study of patients with culture
      confirmed infections. However, this pattern may be changing because AGE
      diagnostics are moving away from culture toward rapid nonculture methods. These
      infections are mainly foodborne and therefore preventable, and it is of paramount
      importance that public health surveillance for these infections is consistent and
      reliable.

PMID- 22377327
TI  - Intestinal barrier function in neonatal foals: options for improvement.
AB  - Gastrointestinal defence in the new-born is limited in comparison to adults, due
      to an immature epithelial barrier function and deficits in both innate and
      adaptive immune responses. Consequently, neonates (including foals) are at
      increased risk of disturbance to mucosal homeostasis during initial intestinal
      colonisation that may lead to excessive inflammation and bacterial translocation
      into the bloodstream, resulting in septicaemia. Bacterial recognition by Pattern
      Recognition Receptors (PRRs) and their downstream regulation of cytokine release
      have been shown to be pivotal for gastrointestinal mucosal homeostasis and the
      development of a functional intestinal barrier. Evidence suggests that selective
      PRR agonists limit the inflammatory responses and improve epithelial barrier
      function. Milk, and in particular colostrum, contain a broad array of
      oligosaccharides which seem to act as PRR agonists. This class of compounds forms
      a source for new dietary formulas that may orchestrate gut colonisation by the
      commensal flora in the early phase of life and so reduce the risks of
      inflammation and pathogen invasion.

PMID- 22377328
TI  - Involvement of matrix metalloproteinase-2 in medial hypertrophy of pulmonary
      arterioles in broiler chickens with pulmonary arterial hypertension.
AB  - Medial hypertrophy of pulmonary arterioles during pulmonary arterial hypertension
      (PAH) in humans is associated with enhanced proliferation of smooth muscle cells
      (SMCs). Elevated matrix metalloproteinase (MMP)-2 has been found in pulmonary
      artery SMCs (PA-SMCs) in humans with idiopathic PAH, leading to the hypothesis
      that MMP-2 contributes to the proliferation and migration of vascular SMCs in the
      pathogenesis of PAH. Rapidly growing meat-type (broiler) chickens provide a model
      of spontaneous PAH. The present study was conducted to determine whether MMP-2 is
      involved in the medial hypertrophy of pulmonary arterioles in this model.
      Cultured PA-SMCs from normal birds were used to evaluate the effect of MMPs on
      cell proliferation. Gelatin zymography showed that endothelin (ET)-1-induced
      proliferation of PA-SMCs was concomitant with increased pro- and active MMP-2
      production. Reverse transcription PCR demonstrated upregulation of MMP-2 mRNA.
      However, PA-SMC proliferation was inhibited by the MMP inhibitors doxycycline and
      cis-9-octadecenoyl-N-hydroxylamide. In vivo experiments revealed a significant
      increase of MMP-2 expression in hypertrophied pulmonary arterioles of PAH broiler
      chickens, which was positively correlated with wall thickness and medial
      hypertrophy. MMP-2 may contribute to medial hypertrophy in pulmonary arterioles
      during PAH in broiler chickens by enhancing the proliferation of vascular SMCs.

PMID- 22377330
TI  - Unilateral autoscopic phenomena as a lateralizing sign in focal epilepsy.
AB  - Positive autoscopic phenomena - autoscopy, heautoscopy and out-of-body experience
      - may occur in a variety of diseases and also in physiological conditions. They
      are a rare but probably underreported phenomenon in focal epilepsies. Here, we
      investigate whether ictal lateralized autoscopic phenomena give lateralizing
      information about the underlying epileptic focus. We present the cases of seven
      patients from our center who experienced ictal lateralized autoscopic phenomena
      and analyzed their focus lateralization and localization of the underlying brain
      lesion. In addition, we reviewed seven cases published in German and English
      language literature. In the total group of 14 patients with ictal lateralized
      autoscopic phenomena, 12 (85.7%) of them had a well-defined epileptic focus
      contralateral to the side of the autoscopic appearance. Therefore, the data point
      to an association between ictal lateralized autoscopy and contralateral epileptic
      focus.

PMID- 22377331
TI  - Mismatch negativity for speech sounds in temporal lobe epilepsy.
AB  - The mismatch negativity (MMN) is an electrophysiological trace of change
      detection, measured by electroencephalography (EEG), and is a reliable marker for
      pre-attentive auditory sensory memory. We used a phonetic oddball paradigm in
      patients with temporal lobe epilepsy (TLE) to elicit the MMN response at fronto
      central sites and the mismatch positivity (MMP) response at mastoid sites. The
      MMN in 26 patients was compared with that of 26 age- and gender-matched healthy
      control participants. Electroencephalography responses were recorded during the
      presentation of speech sounds: the vowels 'a' and 'o' in alternation. Average
      waveforms were obtained for standard and deviant trials. We found that the MMP
      response at bilateral mastoid sites was reduced, whereas the MMN response at
      fronto-central sites did not change significantly. These results support the view
      that the MMN is generated by separable sources in the frontal and temporal lobes
      and that these sources are differentially affected by TLE.

PMID- 22377332
TI  - Primary headache and epilepsy: a multicenter cross-sectional study.
AB  - The prevalence and characteristics of interictal headache, epilepsy and
      headache/epilepsy comorbidity were assessed in 858 women and 309 men aged 18-81
      years from headache and epilepsy centers in Italy. The research hypothesis was
      that comorbidity among patients with either disorder would be expected to be
      higher than in the general population. Interictal headache was diagnosed in 675
      cases (migraine 482; tension-type headache 168; other types 25), epilepsy in 336
      (partial 171; generalized 165) and comorbidity in 156 (1.6% from headache
      centers; 30.0% from epilepsy centers). Patients with epilepsy, headache and
      comorbidity differed in a number of demographic and clinical aspects. However,
      for both headache and epilepsy, a family history of the same clinical condition
      was equally prevalent in patients with and without comorbidity. These findings do
      not support the purported association between headache and epilepsy.

PMID- 22377337
TI  - Ruminal protozoal contribution to the duodenal flow of fatty acids following
      feeding of steers on forages differing in chloroplast content.
AB  - Ruminant products are criticised for their SFA content relative to PUFA, although
      n-6:n-3 PUFA is desirable for human health ( < 4). Rumen protozoa are rich in
      unsaturated fatty acids due to engulfment of PUFA-rich chloroplasts. Increasing
      the chloroplast content of rumen protozoa offers a potentially novel approach to
      enhance PUFA flow to the duodenum and subsequent incorporation into meat and
      milk. We evaluated protozoal contribution to duodenal n-3 PUFA flow due to
      intracellular chloroplast content. A total of six Holstein * Friesian steers were
      fed, in a two-period changeover design, either straw:concentrate (S:C, 60:40; DM
      basis; S:C, low chloroplast) or fresh perennial ryegrass (PRG; high chloroplast).
      Following 12 d adaptation to diet, ruminal protozoal and whole duodenal samples
      were obtained. N and fatty acid content of whole duodenum and rumen protozoal
      samples were assessed and protozoal 18S rDNA quantitative PCR performed, enabling
      calculation of protozoal N flow. The ratio of individual fatty acids:N in rumen
      protozoal samples was calculated to obtain protozoal fatty acid flows. Based on
      total fatty acid flow, contribution (%) of protozoa to individual fatty acid
      flows was calculated. Protozoal fatty acid data and microscopical observations
      revealed that protozoa were enriched with 18 : 3n-3 following PRG feeding,
      compared with the S:C diet, due to increased intracellular chloroplast content.
      However, duodenal protozoal 18S rDNA concentration post PRG feeding was low,
      indicating rumen retention of the protozoa. Nutrition influences the 18 : 3n-3
      content of protozoa; the challenge is to increase protozoal flow to the small
      intestine, while maintaining sustainable rumen densities.

PMID- 22377333
TI  - Glioblastoma: clinical characteristics, prognostic factors and survival in 492
      patients.
AB  - OBJECTIVE: Glioblastoma is the most common and most malignant primary brain tumor
      in adults. The only overall accepted independent prognostic factors are patient
      age and performance. We present a large single institution patient series
      examined for prognostic factors using uni- and multivariate survival analysis.
      METHODS: 492 patients were included who underwent craniotomy for newly diagnosed
      glioblastoma WHO grade IV between 1990 and 2007 at our department. The
      association to patient survival was estimated using log-rank test for univariate
      analysis and cox regression method for multivariate analysis. RESULTS: Median
      patient age was 62 years (mean: 60.4 years, range: 22-93 years), the male: female
      ratio was 1.26:1. Primary genesis was found in 91.0% of cases. A multifocal tumor
      was present in 110 cases (22.4%). The median pre- and post-operative Karnofsky
      Performance Score was 70. Total tumor resection was performed in 288 cases
      (58.5%), subtotal removal in 134 cases (27.2%). The following parameters were
      significantly associated with survival in univariate analysis: age, performance,
      primary genesis, multifocal tumor, neurological deficit, neuropsychological
      findings, seizures, incidental finding, total or subtotal resection,
      radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide, re
      craniotomy, second tumor in patient history. The following parameters were
      significantly associated with survival in multivariate analysis: age,
      performance, multifocal tumor, total or subtotal resection, radiotherapy,
      chemotherapy, combined radio-/chemotherapy with temozolomide. CONCLUSION: In
      addition to patient age and performance, we identified multiple lesions and
      resection status as independent prognostic factors. Radiotherapy, chemotherapy
      and combined radio-/chemotherapy with temozolomide were significantly associated
      with prolonged survival.

PMID- 22377339
TI  - Effect size estimation: methods and examples.
AB  - BACKGROUND: While the p-value will tell the reader a study's results are
      statistically significant, it does not provide any information about the
      practical or clinical importance of the findings. Furthermore, p-values are
      influenced by sample size. They are more likely to be significant when sample
      size is large and less likely if the sample is small. Effect size estimates, on
      the other hand, are not sensitive to sample size and provide information about
      the direction and strength of the relationship between variables (e.g., a
      treatment and an outcome). In addition to providing valuable clinical information
      about study findings, effect size estimates can provide a common metric to
      compare results across studies. Despite their usefulness, effect size estimates
      are often not reported as part of the research results. Consequently, effect
      sizes often have to be calculated based on summary and test statistics reported
      in research articles. RESULTS: This article provides the formulas utilized to
      directly calculate common effective size estimates using summary statistics
      reported in research studies, as well as methods to more indirectly estimate
      these effect sizes when basis summary statistics are not reported. In addition we
      present formulas to compute the corresponding confidence interval for each effect
      size.

PMID- 22377341
TI  - A harm reduction paradox: comparing China's policies on needle and syringe
      exchange and methadone maintenance.
AB  - BACKGROUND: China has launched methadone maintenance treatment (MMT) and needle
      and syringe exchange programmes (NSEP) as part of the country's HIV prevention
      strategy amongst injection drug users. MMT is expanding, with backing from
      multiple government ministries, however, NSEP have received less political
      support and funding. METHODS: Semi-structured, serial interviews were conducted
      with key informants, knowledgeable about China's harm reduction policies.
      Concurrent content analysis allowed for revision of the interview guide
      throughout the data collection process. This was combined with a systematic
      analysis of official government policy documents on NSEP and MMT, including white
      papers, legal documents, and policy statements. FINDINGS: Early consensus between
      public security and public health sectors regarding methadone's dual use in HIV
      prevention as well as method of drug control created broad institutional support
      for MMT programmes amongst policy makers. In contrast, NSEP were seen as
      satisfying only the HIV prevention goals of the public health sector, and were
      perceived as condoning illicit drug use. Furthermore, NSEP's roots in China, as
      an experimental collaboration with international groups, created suspicion
      regarding its role in China's drug control policy. NSEP and MMT's distinct paths
      to policy development are reflected in the complex and occasionally contradictory
      nature of China's harm reduction strategy. CONCLUSIONS: These discrepancies
      highlight the need for a more politically sustainable and comprehensive
      integration of harm reduction projects. Recommendations include improved
      evaluation methods for NESP, NSEP-MMT cross-referral system, and stronger NSEP
      advocacy within the non-profit and public health sectors.

PMID- 22377344
TI  - Novel approach to complex pulmonary arteriovenous malformation embolization using
      detachable coils and Amplatzer vascular plugs.
AB  - INTRODUCTION: We evaluated the feasibility of a modified embolization technique
      of pulmonary arteriovenous malformations (PAVM) using venous sac embolization
      with detachable coils combined with the feeding artery embolization with the
      Amplatzer vascular plug (AVP). MATERIALS AND METHODS: We retrospectively studied
      technical and clinical success in the treatment of 11 complexe PAVMs. We recorded
      number and size of feeding arteries and draining vein, the last prior and post
      treatment in the follow up CT, size of PAVMs; and the number of devices needed to
      occlude each PAVM. RESULTS: 11 complexe PAVM were treated with detachable coils
      to venous sac embolization followed by AVP to embolize feeding arteries. In all
      but one case a complete occlusion of the PAVM was angiographically achieved. The
      mean number of feeding vessel was 2.64 +/- 0.92 (2-5). The mean number of coils
      was 7.82 +/- 5.09 (3-20 coils). CT-follow-up, that was possible in 8 patients,
      showed a significant reduction of the draining vein size. The mean diameter
      reduction of the draining vein was 62 +/- 18% varying between 29% and 77%. In all
      but one case with the complexe angioarchitecture the reduction of draining vein
      size close to 70% was achieved. CONCLUSIONS: Our study implies that the venous
      sac embolization using the detachable coils followed by occlusion of the large
      feeding arteries using the AVP is a highly efficient method for the treatment of
      the complex PAVMs with large out-flow vessels and short feeding arteries.

PMID- 22377345
TI  - [Correction of irregular astigmatism with intracorneal ring segments].
AB  - Management of irregular astigmatism with intracorneal rings segments is an
      intrastromal additive technique developed initially for myopia but eventually
      popularized for keratoconus and post LASIK ectasia. ICR's are indicated for rigid
      contact lens intolerance, as an alternative to corneal transplantation. The
      mechanism of action is complex and involves biomechanical changes leading to a
      centering and a flattening of the ectasia. The surgical procedure has become much
      easier thanks to the use of femtosecond lasers. Individualized implantation
      strategies, based on each patient's topographic and tomographic pattern, are
      constantly evolving. Patients' refraction and vision are usually improved in more
      than 70% of cases. Complications remain very rare. Intracorneal ring segments can
      often be combined with other types of keratoplasty, usually in a sequential
      fashion, so as to optimize functional results.

PMID- 22377348
TI  - MRI technique for the snapshot imaging of quantitative velocity maps using RARE.
AB  - A quantitative PGSE-RARE pulse sequence was developed and successfully applied to
      the in situ dissolution of two pharmaceutical formulations dissolving over a
      range of timescales. The new technique was chosen over other existing fast
      velocity imaging techniques because it is T(2) weighted, not T(2)(*) weighted,
      and is, therefore, robust for imaging time-varying interfaces and flow in
      magnetically heterogeneous systems. The complex signal was preserved intact by
      separating odd and even echoes to obtain two phase maps which are then averaged
      in post-processing. Initially, the validity of the technique was shown when
      imaging laminar flow in a pipe. Subsequently, the dissolution of two drugs was
      followed in situ, where the technique enables the imaging and quantification of
      changes in the form of the tablet and the flow field surrounding it at high
      spatial and temporal resolution. First, the complete 3D velocity field around an
      eroding salicylic acid tablet was acquired at a resolution of 98*49 MUm(2),
      within 20 min, and monitored over ~13 h. The tablet was observed to experience a
      heterogeneous flow field and, hence a heterogeneous shear field, which resulted
      in the non-symmetric erosion of the tablet. Second, the dissolution of a fast
      dissolving immediate release tablet was followed using one-shot 2D velocity
      images acquired every 5.2 s at a resolution of 390*390 MUm(2). The quantitative
      nature of the technique and fast acquisition times provided invaluable
      information on the dissolution behaviour of this tablet, which had not been
      attainable previously with conventional quantitative MRI techniques.

PMID- 22377349
TI  - Characterizing linkage disequilibrium and evaluating imputation power of human
      genomic insertion-deletion polymorphisms.
AB  - BACKGROUND: Indels are an important cause of human variation and central to the
      study of human disease. The 1000 Genomes Project Low-Coverage Pilot identified
      over 1.3 million indels shorter than 50 bp, of which over 890 were identified as
      potentially disruptive variants. Yet, despite their ubiquity, the local genomic
      characteristics of indels remain unexplored. RESULTS: Herein we describe
      population- and minor allele frequency-based differences in linkage
      disequilibrium and imputation characteristics for indels included in the 1000
      Genomes Project Low-Coverage Pilot for the CEU, YRI and CHB+JPT populations.
      Common indels were well tagged by nearby SNPs in all studied populations, and
      were also tagged at a similar rate to common SNPs. Both neutral and functionally
      deleterious common indels were imputed with greater than 95% concordance from
      HapMap Phase 3 and OMNI SNP sites. Further, 38 to 56% of low frequency indels
      were tagged by low frequency SNPs. We were able to impute heterozygous low
      frequency indels with over 50% concordance. Lastly, our analysis also revealed
      evidence of ascertainment bias. This bias prevents us from extending the
      applicability of our results to highly polymorphic indels that could not be
      identified in the Low-Coverage Pilot. CONCLUSIONS: Although further scope exists
      to improve the imputation of low frequency indels, our study demonstrates that
      there are already ample opportunities to retrospectively impute indels for prior
      genome-wide association studies and to incorporate indel imputation into future
      case/control studies.

PMID- 22377351
TI  - Chicken as reservoir for extraintestinal pathogenic Escherichia coli in humans,
      Canada.
AB  - We previously described how retail meat, particularly chicken, might be a
      reservoir for extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary
      tract infections (UTIs) in humans. To rule out retail beef and pork as potential
      reservoirs, we tested 320 additional E. coli isolates from these meats. Isolates
      from beef and pork were significantly less likely than those from chicken to be
      genetically related to isolates from humans with UTIs. We then tested whether the
      reservoir for ExPEC in humans could be food animals themselves by comparing
      geographically and temporally matched E. coli isolates from 475 humans with UTIs
      and from cecal contents of 349 slaughtered animals. We found genetic similarities
      between E. coli from animals in abattoirs, principally chickens, and ExPEC
      causing UTIs in humans. ExPEC transmission from food animals could be responsible
      for human infections, and chickens are the most probable reservoir.

PMID- 22377354
TI  - Escherichia coli producing CMY-2 beta-lactamase in retail chicken, Pittsburgh,
      Pennsylvania, USA.

PMID- 22377355
TI  - Calreticulin has opposing effects on the migration of human trophoblast and
      myometrial endothelial cells.
AB  - Calreticulin is a calcium binding, endoplasmic reticulum resident protein best
      known for its roles in intracellular calcium homeostasis and the quality control
      processes of the endoplasmic reticulum. There is evidence for a range of
      activities for calreticulin outside the endoplasmic reticulum, including in the
      cytosol, on the surface of different cells types and in the extracellular matrix.
      Recent evidence indicates that human pregnancy is a condition of elevated
      circulating calreticulin. Calreticulin was increased in the plasma of women
      throughout pregnancy compared to the non-pregnant state. Calreticulin was also
      further increased during the hypertensive disorder of human pregnancy, pre
      eclampsia. To clarify the roles of circulating calreticulin in pregnancy and pre
      eclampsia, the aim of this study was to determine the effects of exogenous
      calreticulin on two cell types that are relevant to normal human pregnancy and to
      pre-eclampsia. Human primary myometrial microvascular endothelial cells (UtMVEC
      Myo) and the human trophoblast cell line, HTR8/SVneo, were cultured with
      exogenous calreticulin at concentrations (2 MUg/ml and 5 MUg/ml) comparable to
      that measured in maternal blood. The higher concentration of calreticulin
      significantly increased the migration of the UtMVEC-Myo cells, but significantly
      reduced the migration of the HTR8/SVneo cells. In the presence of only FGF, FBS
      and antibiotics calreticulin at 5 MUg/ml significantly reduced the number of
      UtMVEC-Myo cells during in vitro culture for 120 h. These results demonstrate
      that exogenous calreticulin can alter both HTR8/SVneo and UtMVEC-Myo cell
      functions in vitro at a (patho-) physiologically relevant concentration.
      Increased calreticulin may also contribute to altered functions of both cell
      types during pre-eclampsia.

PMID- 22377356
TI  - A re-analysis of the iron content of plant-based foods in the United Kingdom.
AB  - In the UK contemporary estimates of dietary Fe intakes rely upon food Fe content
      data from the 1980s or before. Moreover, there has been speculation that the
      natural Fe content of foods has fallen over time, predominantly due to changes in
      agricultural practices. Therefore, we re-analysed common plant-based foods of the
      UK diet for their Fe content (the '2000s analyses') and compared the values with
      the most recent published values (the '1980s analyses') and the much older
      published values (the '1930s analyses'), the latter two being from different
      editions of the McCance and Widdowson food tables. Overall, there was remarkable
      consistency between analytical data for foods spanning the 70 years. There was a
      marginal, but significant, apparent decrease in natural food Fe content from the
      1930s to 1980s/2000s. Whether this represents a true difference or is analytical
      error between the eras is unclear and how it could translate into differences in
      intake requires clarification. However, fortificant Fe levels (and fortificant Fe
      intake based upon linked national data) did appear to have increased between the
      1980s and 2000s, and deserve further attention in light of recent potential
      concerns over the long-term safety and effectiveness of fortificant Fe. In
      conclusion, the overall Fe content of plant-based foods is largely consistent
      between the 1930s and 2000s, with a fall in natural dietary Fe content negated or
      even surpassed by a rise in fortificant Fe but for which the long-term effects
      are uncertain.

PMID- 22377357
TI  - Wls-mediated Wnts differentially regulate distal limb patterning and tissue
      morphogenesis.
AB  - Wnt proteins are diffusible morphogens that play multiple roles during vertebrate
      limb development. However, the complexity of Wnt signaling cascades and their
      overlapping expression prevent us from dissecting their function in limb
      patterning and tissue morphogenesis. Depletion of the Wntless (Wls) gene, which
      is required for the secretion of various Wnts, makes it possible to genetically
      dissect the overall effect of Wnts in limb development. In this study, the Wls
      gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of
      mesenchymal Wls prevented the differentiation of distal mesenchyme and arrested
      limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion
      of ectodermal Wls resulted in agenesis of distal limb tissue and premature
      regression of the distal mesenchyme. These observations suggested that Wnts from
      the two germ layers differentially regulate the pool of undifferentiated distal
      limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts
      sustain mesenchymal cell proliferation and survival in a manner distinct from
      Fgf. Ectodermal Wnts were also shown for the first time to be essential for
      distal tendon/ligament induction, myoblast migration and dermis formation in the
      limb. These findings provide a comprehensive view of the role of Wnts in limb
      patterning and tissue morphogenesis.

PMID- 22377363
TI  - A model for evaluating the social performance of construction waste management.
AB  - It has been determined by existing literature that a lot of research efforts have
      been made to the economic performance of construction waste management (CWM), but
      less attention is paid to investigation of the social performance of CWM. This
      study therefore attempts to develop a model for quantitatively evaluating the
      social performance of CWM by using a system dynamics (SD) approach. Firstly,
      major variables affecting the social performance of CWM are identified and a
      holistic system for assessing the social performance of CWM is formulated in line
      with feedback relationships underlying these variables. The developed system is
      then converted into a SD model through the software iThink. An empirical case
      study is finally conducted to demonstrate application of the model. Results of
      model validation indicate that the model is robust and reasonable to reflect the
      situation of the real system under study. Findings of the case study offer
      helpful insights into effectively promoting the social performance of CWM of the
      project investigated. Furthermore, the model exhibits great potential to function
      as an experimental platform for dynamically evaluating effects of management
      measures on improving the social performance of CWM of construction projects.

PMID- 22377368
TI  - Influence of sporting activity and smoking on peripheral lymph nodes in patients
      with melanoma analyzed by high-resolution ultrasound.
AB  - BACKGROUND: The sonographic examination of peripheral lymph nodes (LNs) plays an
      important role in the preoperative treatment and in the follow-up of patients
      with melanoma. OBJECTIVE: A prospective study including 200 consecutive patients
      with a history of invasive cutaneous melanoma was performed at the Department of
      Dermatology and Allergy, University of Bonn, Germany, to examine the influence of
      sporting activity, physical workload, interferon alfa therapy, smoking habits,
      and infections of the upper respiratory tract on morphology and number of LNs
      analyzed by high-resolution ultrasound. METHODS: Between May 2010 and June 2011,
      106 men and 94 women (mean age 51.1 +/- 12.8 years) were included in this study.
      During their follow-up visits for cutaneous melanoma, high-resolution ultrasound
      examination of cervical, axillary, and inguinal LN regions were performed. LN
      diameters and volumes were measured and correlated with the above given factors.
      RESULTS: Sports-active patients had more LNs in inguinal regions, a higher volume
      and a larger LN diameter, and a higher maximum width of the hypoechoic LN margin
      in comparison with the nonactive patients. Patients with a hard physical workload
      in their occupations had a significantly higher volume of the biggest LN.
      Compared with nonsmoking patients smokers presented higher values in the total
      quantity of the LNs, in the greatest volume of LN, and in the greatest diameter
      of LN in the cervical regions. The other factors had no significant influence on
      the LN parameters. LIMITATIONS: Our study population was too small to comment on
      influencing factors in more detail especially the influences of different
      sporting activities or smoking habits. CONCLUSION: Sporting activity, physical
      workload, and smoking habits as associated cofactors influencing sonomorphologic
      aspects in patients with cutaneous melanoma should always be considered.

PMID- 22377369
TI  - Short-term versus long-term rainfall time series in the assessment of potable
      water savings by using rainwater in houses.
AB  - The main objective of this article is to assess the possibility of using short
      term instead of long-term rainfall time series to evaluate the potential for
      potable water savings by using rainwater in houses. The analysis was performed
      considering rainfall data from 1960 to 1995 for the city of Santa Barbara do
      Oeste, located in the state of Sao Paulo, southeastern Brazil. The influence of
      the rainfall time series, roof area, potable water demand and percentage
      rainwater demand on the potential for potable water savings was evaluated. The
      potential for potable water savings was estimated using computer simulations
      considering a set of long-term rainfall time series and different sets of short
      term rainfall time series. The ideal rainwater tank capacity was also assessed
      for some cases. It was observed that the higher the percentage rainwater demand
      and the shorter the rainfall time series, the larger the difference between the
      potential for potable water savings and the greater the variation in the ideal
      rainwater tank size. The sets of short-term rainfall time series considered
      adequate for different scenarios ranged from 1 to 13 years depending on the roof
      area, percentage rainwater demand and potable water demand. The main finding of
      the research is that sets of short-term rainfall time series can be used to
      assess the potential for potable water savings by using rainwater, as the results
      obtained are similar to those obtained from the long-term rainfall time series.

PMID- 22377374
TI  - Further response from Hoenselaar.

PMID- 22377376
TI  - Evaluation of positron emission tomography as a method to visualize subsurface
      microbial processes.
AB  - Positron emission tomography (PET) provides spatiotemporal monitoring in a
      nondestructive manner and has higher sensitivity and resolution relative to other
      tomographic methods. Therefore, this technology was evaluated for its application
      to monitor in situ subsurface bacterial activity. To date, however, it has not
      been used to monitor or image soil microbial processes. In this study, PET
      imaging was applied as a "proof-of-principle" method to assess the feasibility of
      visualizing a radiotracer labeled subsurface bacterial strain (Rahnella sp.
      Y9602), previously isolated from uranium contaminated soils and shown to promote
      uranium phosphate precipitation. Soil columns packed with acid-purified simulated
      mineral soils were seeded with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG)
      labeled Rahnella sp. Y9602. The applicability of [(18)F]fluoride ion as a tracer
      for measuring hydraulic conductivity and (18)FDG as a tracer to identify
      subsurface metabolically active bacteria was successful in our soil column
      studies. Our findings indicate that positron-emitting isotopes can be utilized
      for studies aimed at elucidating subsurface microbiology and geochemical
      processes important in contaminant remediation.

PMID- 22377378
TI  - Ilheus virus infection in human, Bolivia.

PMID- 22377371
TI  - A systematic approach for discovering novel, clinically relevant bacteria.
AB  - Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial
      identification. Its expanded use has led to increased recognition of novel
      bacterial species. In most clinical laboratories, novel species are infrequently
      encountered, and their pathogenic potential is often difficult to assess. We
      reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during
      February 2006-June 2010, and identified 673 that have <99% sequence identity with
      valid reference sequences and are thus possibly novel species. Of these 673
      isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel
      taxa were recovered from multiple patients, indicating possible clinical
      relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia
      (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This
      systematic approach for recognition of novel species with potential diagnostic or
      therapeutic relevance provides a basis for epidemiologic surveys and improvement
      of sequence databases and may lead to identification of new clinical entities.

PMID- 22377379
TI  - Low-level ganglionated plexus stimulation facilitates atrial fibrillation: in
      vivo and in vitro studies.
AB  - OBJECTIVES: The purpose of the present study was to investigate whether long term
      low level autonomic activation can form electrophysiological substrate for atrial
      fibrillation (AF). METHODS AND RESULTS: In 16 anesthetized open-chest dogs,
      electrodes on the anterior right ganglionated plexuses (GP) and superior left GP
      allowed 6-h low-level GP stimulation (LL-GPS) inducing a 10% decrease in sinus
      rate. Similar low-level stimulation (without myocardial capture) was delivered to
      the myocardium remote from the GP for 6h in another 16 dogs as control group. LL
      GPS: a) induced shortening of the atrial effective refractory period and increase
      of the window of vulnerability for AF; b) significantly increased acetylcholine
      regulated potassium current (I(KACh)) at left superior pulmonary vein (LSPV)
      while reduced the density of L-type calcium current (I(CaL)) at LSPV and both
      atria, the protein expression of the channel subunit showed a consistent
      alteration, however both without significant changes in mRNA level. CONCLUSIONS:
      Six-hour LL-GPS induced significant changes in atrial electrophysiology and
      facilitated the initiation of AF, indicating that long-term low level autonomic
      activation would form electrophysiological substrate for AF. The underlying
      mechanism may be associated with a post-transcriptional regulation of increased
      I(KACh) and decreased I(CaL).

PMID- 22377384
TI  - Riluzole produces distinct anxiolytic-like effects in rats without the adverse
      effects associated with benzodiazepines.
AB  - In this study, we investigated the anxiolytic-like effect of riluzole using three
      different innate anxiety models in rats. In the elevated plus-maze test, riluzole
      significantly increased the time spent in, and entries into, the open arm after
      60 min administration. This finding was supported by results obtained from
      light/dark and open-field tests. The magnitude of the anxiolytic-like effects of
      riluzole in each of the behavioral models was similar to those produced by a
      benzodiazepine, diazepam, suggesting that riluzole has a robust anxiolytic-like
      activity in rats. To clarify the involvement of sodium channels in this
      anxiolytic activity, we examined the effect of a co-administered sodium channel
      activator, veratrine. The anxiolytic-like action of riluzole was diminished by
      veratrine in the elevated plus-maze, light/dark and open-field tests. Based on
      these results, it is suggested that the anxiolytic mechanism of riluzole is
      clearly distinct from that of diazepam. In addition, to examine whether riluzole
      directly and non-selectively affected the GABA(A)-benzodiazepine receptor
      complex, we performed three behavioral tests (footprint analysis, Y-maze test and
      the ethanol-induced sleeping time test) that are closely related to the GABA(A)
      benzodiazepine pathways. In contrast to diazepam, riluzole produced no
      significant effects in these tests. Here, we provide the first report
      demonstrating that riluzole produces distinct anxiolytic-like effects in rats
      without the adverse effects associated with benzodiazepines.

PMID- 22377385
TI  - A highly selective and colorimetric assay of lysine by molecular-driven gold
      nanorods assembly.
AB  - In this contribution, a simple, rapid, colorimeteric and selective assay for
      lysine was achieved by a controllable end-to-end assembly of gold nanorods
      (AuNRs) in the presence of Eu(3+) and lysine. This one-pot end-to-end assembly of
      11-mercaptoundecanoic acid (MUA) modified AuNRs was occurred in Britton-Robinson
      buffer of pH 6.0, which involves the coordination binding between Eu(3+) and COO(
      ) groups as well as the electrostatic interaction of the COO(-) groups of MUA
      with the -NH(3)(+) group of lysine. As monitored by absorption spectra, scanning
      electron microscopic (SEM) images and dynamic light scattering (DLS) measurement,
      the end-to-end chain assembly results in large red-shift in the longitudinal
      plasmon resonance absorption (LPRA), giving red-to-blue color change of AuNRs.
      Importantly, it was found that the red-shift of LPRA is linearly proportional to
      the concentrations of lysine in the range of 5.0*10(-6)-1.0*10(-3)M with the
      limit of detection (LOD) being 1.6*10(-6)M (3sigma/k). This red-shift of LPRA is
      highly selective, making it possible to develop a rapid, selective and visual
      assay for lysine in food samples.

PMID- 22377387
TI  - Infection control systems in transition: the challenges for post-Soviet Bloc
      countries.
AB  - BACKGROUND: Just two decades ago, 30 of today's countries in Europe and Asia had
      socialist governments under Soviet dominance or direct administration. Intensive
      health system reforms have altered infection control in many of these countries.
      However, much of the literature from these countries is difficult to access by
      international scientists. AIM: To summarize existing infection control policies
      and practices in post-Soviet Bloc countries. METHODS: In addition to PubMed and
      Google search engines, we explored local websites and grey literature. In total,
      192 references published in several languages were reviewed. FINDINGS: Infection
      control in these countries is in the midst of transition. Three groups of
      countries were identified. First, Eastern European and Baltic countries building
      surveillance systems for specific pathogens and antibiotic use; second, European
      post-Soviet Bloc countries focusing on the harmonization of recently established
      infection control infrastructure with European surveillance programmes; third,
      countries such as those formerly in the Union of Soviet Socialist Republics,
      Mongolia and post-conflict Eastern European countries that are in the first
      stages of reform. Poor commitment, resource scarcity and shortages of expertise
      were identified. Underreporting of official infection control statistics is
      widespread. CONCLUSIONS: Guidance from international organizations has been
      crucial in initiating and developing contemporary infection control programmes.
      More support from the international community will be needed for the third group
      of countries, where infection control has remained a neglected issue.

PMID- 22377389
TI  - Project Impact: a pharmacotherapy pilot trial investigating the abstinence and
      treatment adherence of Latino light smokers.
AB  - Light smoking is particularly prevalent among Latino smokers. Nicotine
      replacement (NRT) and varenicline are effective medications for smoking cessation
      for moderate-heavy smokers but have not been tested in light smokers, and thus,
      there are no treatment guidelines for use with light smokers. This pilot trial
      tested the efficacy of NRT and varenicline in increasing smoking abstinence among
      Latino light smokers. A 3-group (NRT, varenicline, and varenicline-placebo)
      randomized design was used, and Latino light smokers (<=10 cigarettes per day)
      received 12 weeks of treatment, which included a culturally informed behavioral
      health session and ongoing medication management visits. At follow-up, there were
      no abstinent participants in the placebo and NRT groups. However, 30% of
      participants in the varenicline group were abstinent at the 3-, 4-, and 6-month
      follow-up. This study represents the only investigation that specifically targets
      Latino light smokers using these treatments and characterizing their treatment
      adherence.

PMID- 22377390
TI  - Screening services for alcohol misuse and abuse at four-year colleges in the U.S.
AB  - We examine the prevalence of screening for student alcohol misuse/abuse among 333
      U.S. colleges via a survey of campus leaders. We also use latent class modeling
      to identify classes of colleges based on screening practices. We found that most
      colleges conduct screening after a student is involved in an alcohol-related
      incident, and about 50% of colleges screen students at regular health care
      visits. Legal, health care, and housing staff are trained in screening at nearly
      all colleges; other key personnel were trained at about one third of colleges. We
      identified four classes of colleges: 62% of colleges fit in a class that had many
      screening components in place, 9% in a class with very limited services, and the
      remainder (29%) fit in 2 middle classes. Although most colleges had many alcohol
      misuse/abuse screening components in place, more than one third show need for
      improvement in how, where, and when screening is conducted.

PMID- 22377391
TI  - A double-blind, placebo-controlled trial of modafinil for cocaine dependence.
AB  - This is a randomized, double-blind, placebo-controlled study of modafinil
      treatment for cocaine dependence. Patients (N = 210) who were actively using
      cocaine at baseline were randomized to 8 weeks of modafinil (0 mg/day, 200
      mg/day, or 400 mg/day) combined with once-weekly cognitive-behavioral therapy.
      Our primary efficacy measure was cocaine abstinence, based on urine
      benzoylecgonine (BE) levels, with secondary measures of craving, cocaine
      withdrawal, retention, and tolerability. We found no significant differences
      between modafinil and placebo patients on any of these measures. However, there
      was a significant gender difference in that male patients treated with 400 mg/day
      tended to be more abstinent than their placebo-treated counterparts (p = .06).
      Our negative findings might be explained by gender differences and/or inadequate
      psychosocial treatment intensity in patients with severe cocaine dependence.

PMID- 22377393
TI  - High-dose rosiglitazone is pro-atherogenic in cholesterol-fed rabbits.

PMID- 22377394
TI  - Characteristics of earlier atherosclerotic involvement in adolescent patients
      with Kawasaki disease and coronary artery lesions: significance of gray scale
      median on B-mode ultrasound.
AB  - OBJECTIVE: To test the hypothesis that textural changes in the carotid intima
      media complex (IMC) detected by B-mode ultrasound are associated with the
      difference of remodeling process in earlier atherosclerotic involvement in
      patients with Kawasaki disease (KD) and coronary artery lesions (CALs). METHODS:
      Eighteen patients with KD and CALs (mean age 17.2 years), 17 patients with
      heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age
      matched healthy controls (Cont) were assessed and compared for carotid intima
      media thickness (CIMT), elastic property (E(p)), and first- and second-order
      statistics. RESULTS: KD showed significantly higher gray scale median (GSM) than
      FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower
      angular second moment than Cont, but no significant difference was found between
      KD and FH. CONCLUSION: Higher GSM in KD may indicate alteration of tissue
      components and heterogeneity of IMC, suggesting the development of
      arteriosclerotic vascular remodeling after vasculitis. This is distinct from that
      of atherosclerosis with lower GSM often observed in FH.

PMID- 22377395
TI  - Serum levels of IgG4 and soluble interleukin-2 receptor in patients with
      abdominal and thoracic aortic aneurysm who undergo coronary angiography.

PMID- 22377396
TI  - Roles of mating behavioural interactions and life history traits in the
      competition between alien and indigenous whiteflies.
AB  - Interference competition between closely related alien and indigenous species
      often influences the outcome of biological invasions. The whitefly Bemisia tabaci
      species complex contains >=28 putative species and two of them, Mediterranean
      (MED, formally referred to as the 'Q biotype') and Middle East-Asia Minor 1
      (MEAM1, formally referred to as the 'B biotype'), have recently spread to much of
      the world. In many invaded regions, these species have displaced closely related
      indigenous whitefly species. In this study, we integrated laboratory population
      experiments, behavioural observations and simulation modelling to investigate the
      capacity of MED to displace Asia II 1 (AII1, formally referred to as the 'ZHJ2
      biotype'), an indigenous whitefly widely distributed in Asia. Our results show
      that intensive mating interactions occur between MED and AII1, leading to reduced
      fecundity and progeny female ratio in AII1, as well as an increase in progeny
      female ratio in MED. In turn, our population cage experiments demonstrated that
      MED has the capacity to displace AII1 in a few generations. Using simulation
      models, we then show that both asymmetric mating interactions and differences in
      life history traits between the two species contribute substantially to the
      process of displacement. These findings would help explain the displacement of
      AII1 by MED in the field and, together with earlier studies on mating
      interactions between other species of the B. tabaci complex, indicate the
      widespread significance of asymmetric mating interactions in whitefly species
      exclusions. 

PMID- 22377400
TI  - A quantitative structure-property relationship analysis of soot-water partition
      coefficients for persistent organic pollutants.
AB  - Geometrical optimization and electrostatic potential calculations have been
      performed at the HF/6-31G level of theory for investigated persistent organic
      pollutants (POPs). A number of statistically based parameters have been obtained.
      Relationship between soot-water partition coefficients (logK(SC)) of POPs and the
      structural descriptors has been established by the multiple linear regression
      method. The result shows that the quantities derived from electrostatic potential
      V(s)(-)- and V(s,max), together with molecular surface area (A(S)) and the energy
      of the highest occupied molecular orbital (E(HOMO)) can be well used to express
      the quantitative relationship between structure and logK(SC) (QSPR) of POPs.
      Predictive capability of the model has been demonstrated by leave-one-out cross
      validation with the cross-validated correlation coefficient of 0.9797.
      Furthermore, the predictive power of this model was further examined for the
      external test set with the correlation coefficient of 0.9811 between observed and
      predicted logK(SC), validating the robustness and good predictive ability of our
      model. Furthermore, in order to further investigate the applicability of these
      parameters derived from electrostatic potential in prediction of soot-water
      partition coefficient for organic pollutants, eleven polycyclic aromatic
      hydrocarbons (PAHs), eleven polychlorinated biphenyls (PCBs) and nine phenyl urea
      herbicides (PUHs) from other source have also been studied. The QSPR models
      established may provide a new powerful method for predicting soot-water partition
      coefficients (logK(SC)) of organic pollutants.

PMID- 22377401
TI  - Protective effect of Withania somnifera against radiation-induced hepatotoxicity
      in rats.
AB  - The aim of this study was to investigate the protective effect of root extract of
      Withania somnifera (WS) against gamma-irradiation-induced oxidative stress and
      DNA damage in hepatic tissue after whole body gamma-irradiation. Fourty male
      albino rats were divided into four groups. In the control group, rats were
      administered vehicle by tube for 7 consecutive days. The second group were
      administered WS (100mg/kg, by gavage) for 7 consecutive days. Animals in the
      third group were administered vehicle by tube for 7 consecutive days, then
      exposed to single dose gamma-irradiation (6 Gy). The fourth group received WS for
      7 consecutive days, one hour later rats were exposed to gamma-irradiation.
      Irradiation hepatotoxicity was manifested biochemically by an increase in hepatic
      serum enzymes, significant elevation in levels of malondialdehyde (MDA) and total
      nitrate/nitrite NO(x), significant increase in heme oxygenase activity (HO-1), as
      well as a significant decrease in reduced glutathione (GSH) content and the
      activities of antioxidant enzymes, including superoxide dismutase (SOD) and
      glutathione peroxidase (GSHPx) in hepatic tissues. Marked DNA damage was
      observed. WS pretreatment showed significant decrease in serum hepatic enzymes,
      hepatic NO(x) and MDA levels and DNA damage, significant HO-1 induction and
      significant increase in SOD, GSHPx activities and GSH content compared to
      irradiated group. These observations suggest that WS could be developed as a
      potential preventive drug for ionizing irradiation induced hepatotoxicity
      disorders via enhancing the antioxidant activity and induction of HO-1.

PMID- 22377402
TI  - Ecological risk assessment of on-site soil washing with iron(III) chloride in
      cadmium-contaminated paddy field.
AB  - On-site soil washing with iron(III) chloride reduces Cd levels in soil, and thus
      the human health risks caused by Cd in food. However, it may threaten aquatic
      organisms when soil washing effluent is discharged to open aquatic systems.
      Therefore, we conducted trial-scale on-site soil washing and ecological risk
      assessment in Nagano and Niigata prefectures, Japan. The ecological effect of
      effluent water was investigated by two methods. The first was bioassay using
      standard aquatic test organisms. Twice-diluted effluent water from the Nagano
      site and the original effluent water from the Niigata site had no significant
      effects on green algae, water flea, caddisfly, and fish. The safe dilution rates
      were estimated as 20 times and 10 times for the Nagano and Niigata sites,
      respectively, considering an assessment factor of 10. The second method was
      probabilistic effect analysis using chemical analysis and the species sensitivity
      distribution concept. The mixture effects of CaCl(2), Al, Zn, and Mn were
      considered by applying a response additive model. The safe dilution rates,
      assessed for a potentially affected fraction of species of 5%, were 7.1 times and
      23.6 times for the Nagano and Niigata sites, respectively. The actual dilution
      rates of effluent water by river water at the Nagano and Niigata sites were 2200
      67,000 times and 1300-110,000 times, respectively. These are much larger than the
      safe dilution rates derived from the two approaches. Consequently, the ecological
      risk to aquatic organisms of soil washing is evaluated as being below the concern
      level.

PMID- 22377404
TI  - Subgingival microbial profiles of generalized aggressive and chronic periodontal
      diseases.
AB  - OBJECTIVE: The aim of this study was to distinguish between generalized
      aggressive (GAgP) and chronic periodontitis (CP) based on the subgingival
      microbial profiles predominant in these diseases. METHODS: Two-hundred and sixty
      subjects, 75 with GAgP and 185 with CP were recruited. Full-mouth clinical
      measurements were recorded. Individual subgingival plaque samples were taken from
      7 sites per subject and analyzed for the prevalence and levels of 51 species by
      chequerboard. Differences between groups were examined by the Mann-Whitney test.
      Associations between bacterial species and GAgP were examined by logistic
      regression analysis. RESULTS: Actinomyces gerensceriae, Actinomyces israelli,
      Eubacterium nodatum and Propionibacterium acnes were detected in significantly
      greater counts in GAgP, whereas Capnocytophaga ochracea, Fusobacterium
      periodonticum, Staphylococcus aureus and Veillonella parvula were more
      predominant in CP patients (adjusted p < 0.001). E. nodatum (at mean levels >=4 *
      10(5)) increased significantly the probability of a subject being diagnosed with
      GAgP than CP (OR 2.44 [0.96-6.20]), whereas P. gingivalis (OR 0.34 [0.11-0.93])
      and T. denticola (OR 0.35 [0.11-0.94]) were associated with CP. CONCLUSIONS: Very
      few subgingival species differed in prevalence and/or levels between GAgP and CP
      in this sample population. In particular, E. nodatum was strongly related to
      GAgP, whereas P. gingivalis and T. denticola were associated with CP.

PMID- 22377405
TI  - Regulatory control of glycopyrrolate in performance horses using validated
      UHPLC/MS-MS methods.
AB  - We describe a validated, rapid, sensitive, and specific UHPLC-MS/MS method to
      detect and quantify glycopyrrolate in 0.5 mL of horse urine. Further, we
      investigated the elimination of glycopyrrolate in urine after both intravenous
      and oral administration of clinically relevant doses to Thoroughbred horses.
      Quantification was performed by weighted, linear regression analysis using a
      deuterated analogue of glycopyrrolate as internal standard (IS). The method was
      characterized by a linear range of 5-2500 pg/mL, a lower limit of quantification
      of 5 pg/mL and a limit of detection of 1 pg/mL. The intra and inter-batch
      imprecisions were <10% RSD and accuracy of the method ranged between 94 and 104%.
      Glycopyrrolate remained detectable in urine samples collected through 168 h after
      intravenous administration and through 24h after oral administration. Analytical
      method validation requirements for linearity, specificity, precision, accuracy,
      stability, dilution integrity, matrix effect, and ruggedness have been fulfilled.
      The urine method described in this report is simple and efficient and is the
      first reported method with sufficient sensitivity, accuracy, and precision to
      regulate the use of glycopyrrolate in urine samples collected more than one day
      after dosing of horses. Urine to plasma glycopyrrolate concentration ratios were
      calculated and were approximately 100:1 in samples collected from 24h through the
      end of sample collection.

PMID- 22377406
TI  - Development and validation of a sensitive LC-MS/MS assay for simultaneous
      quantitation of ranolazine and its three metabolites in human plasma.
AB  - A rapid, sensitive and reliable LC-MS/MS method was developed and validated for
      the simultaneous determination of ranolazine and its three metabolites, CVT-2514,
      CVT-2738, and CVT-4786, in human plasma. The plasma samples were prepared by
      protein precipitation. Chromatographic separation was achieved on a Gemini C(18)
      column (50 mm * 2.0 mm, 5 MUm) using methanol: 5 mM ammonium acetate as the
      mobile phase with gradient elution. Mass detection was carried out by
      electrospray ionization in both positive and negative ion multiple reaction
      monitoring (MRM) modes. The calibration curves were linear over a concentration
      range of 4-2000 ng/mL for ranolazine, 4-1000 ng/mL for CVT-2514 and CVT-2738 and
      8-1000 ng/mL for CVT-4786. The intra-day and inter-day accuracy and precision
      were within the acceptable limits of +/-15% at all concentrations. The method was
      successfully applied for the simultaneous estimation of ranolazine and its three
      metabolites in human plasma from a clinical pharmacokinetics study.

PMID- 22377407
TI  - Purification strategies, characteristics and thermodynamic analysis of a highly
      thermostable alkaline protease from a salt-tolerant alkaliphilic actinomycete,
      Nocardiopsis alba OK-5.
AB  - An alkaline protease from salt tolerant alkaliphilic actinomycetes, Nocardiopsis
      alba strain OK-5 was purified to homogeneity by 27 and 13 fold with a yield of 35
      and 13% using two-steps and one-step method, respectively. The purification
      methods involved hydrophobic interaction on phenyl sapharose matrix. The apparent
      molecular mass was 20 kDa. The temperature optimum shifted from 70 to 80 degrees
      C in 4M NaCl and 30% Na-glutamate, with significant stability at 60-80 degrees C
      in Na-glutamate. Deactivation rate constant (K(d)) increased and half life
      (t(1/2)) decreased with the increasing temperatures from 37 to 80 degrees C. The
      order of stability was: 30% Na-glutamate>4M NaCl>2M NaCl>0M NaCl. The enzyme was
      stable even at 80 degrees C in 30% Na-glutamate with K(d) 4.11 and t(1/2) 168.64
      min. The activation energies (E), enthalpy (DeltaH*) and entropy (DeltaS*) for
      protease deactivation in with Na-glutamate were 31.97 kJ/mole, 29.23 kJ/mole and 
      211.83 J/mole, respectively. The change in free energy (DeltaG*) for protease
      deactivation at 60 degrees C in 30% Na-glutamate was 101.70 kJ/mole. Protease had
      the highest activity and stability at pH 10-11. While the enzyme was highly
      resistant against chemical denaturation, it had varied responses to metal ions.
      Complete inhibition by PMSF confirmed serine nature of the protease. Na
      glutamate, H(2)O(2), beta-mercaptoethanol and different surfactants enhanced the
      activity.

PMID- 22377411
TI  - Shared human/rabbit ligands for rabbit hemorrhagic disease virus.

PMID- 22377408
TI  - Seroprevalence of antibodies against Taenia solium cysticerci among refugees
      resettled in United States.
AB  - Neurocysticercosis (NCC) is a disease caused by central nervous system infection
      by the larval stage of the pork tapeworm, Taenia solium. In developing countries,
      NCC is a leading cause of adult-onset epilepsy. Case reports of NCC are
      increasing among refugees resettled to the United States and other nations, but
      the underlying prevalence among refugee groups is unknown. We tested stored serum
      samples from the Centers for Disease Control and Prevention Migrant Serum Bank
      for antibodies against T. solium cysts by using the enzyme-linked
      immunoelectrotransfer blot. Seroprevalence was high among all 4 populations
      tested: refugees from Burma (23.2%), Lao People's Democratic Republic (18.3%),
      Bhutan (22.8%), and Burundi (25.8%). Clinicians caring for refugee populations
      should suspect NCC in patients with seizure, chronic headache, or unexplained
      neurologic manifestations. Improved understanding of the prevalence of epilepsy
      and other associated diseases among refugees could guide recommendations for
      their evaluation and treatment before, during, and after resettlement.

PMID- 22377413
TI  - [Financial and medicolegal impact of dental trauma].
AB  - INTRODUCTION: Dental injuries are among the most common complications of general
      anesthesia. Yet few studies have assessed the costs and factors that involve the
      responsibility of the anesthetist. STUDY DESIGN: A retrospective study was
      conducted at the university hospital of Reims on 46 cases of dental injuries
      directly related to anaesthesia. RESULTS: Ten patients made a claim for
      compensation. Two of them have received compensation following a medical
      expertise, which revealed for the first patient a possible alternative to general
      anaesthesia, and the second, hardware failure of intubation. The Administrative
      Court was entered once in 9 years. The global insurance-cost amounts to 4476
      euros for all patients. The review of all cases of anaesthesia shows clearly that
      the dental claims are associated with a significant under clinical evaluation of
      dental status and criteria for difficult intubation during the anaesthesia. The
      information to the patient on this risk is not obvious from reading the
      anaesthesia records. No mouth guard was used. CONCLUSION: This work proves that
      the statements of caution are the most common and a minority of dental trauma
      lead to a claim. Claims are due to the high cost of dental care repair. The
      proportion of patients receiving benefits is extremely low. Medical expertise is
      an essential part of the evaluation of medical responsibilities. No compensation
      was paid without expertise. The lack of physical examination and information are
      contrary to our professional obligations and may involve our responsibility. The
      lack of patient information is not generated for compensation to the extent that
      the consequences of failure are easily dental weighed against the benefits of the
      entire medical-surgical procedure that the patient has agreed.

PMID- 22377414
TI  - [French clinical guidelines for prevention of perianaesthetic dental injuries:
      long text].
AB  - INTRODUCTION: Dental injuries represent the most common claims against the
      anaesthesiologists. Dental lesions are frequent complications of orotracheal
      intubation and major causal factors are, firstly, preexisting poor dentition,
      and, secondly, difficult laryngoscopy and tracheal intubation. The aim of this
      work was to prioritize propositions for prevention in perianaesthetic dental
      injury and for care in case of dental trauma. METHOD: A GRADE consensus procedure
      consisting of three rounds was conducted. A purposively selected heterogeneous
      panel (n=15) of experts, comprising 10 practitioners in anesthesiology, one
      practitioner who is jurist and anaesthesiologist, two practitioners in
      maxillofacial surgery, and two practitioners in dentist surgery. In cases where
      the data did not appear conclusive, recommendations were based on the consensus
      opinion of the board members. The guidelines represent the best current evidence
      based on literature search and professional opinion. RESULTS: The entire panel
      completed all three rounds and 31 plus six propositions were written for adult
      and paediatric clinical practice in anaesthesiology, respectively. The experts
      highlight the interest of preoperative visit for minimizing dental injuries: the
      practitioner must identify risk factors for difficult intubation and ventilation,
      describe precisely patient's preoperative dental condition, including upper
      incisor most commonly involved teeth in dental trauma. Patients have to be
      informed by practitioner for risk dental injury and anaesthesiology staff must
      choose his anesthesia protocol before the induction of intubation narcosis,
      avoiding insufficient anaesthesia and lack of experience by the
      anaesthesiologist. The choice of accurate proceeding during laryngoscopy,
      tracheal intubation and extubation for example, can aid in the prevention of
      dental injury, reduce the number of claims and the cost of litigation process.
      DISCUSSION: These guidelines delineate an approach for the prevention of
      perianaesthetic dental trauma and for the immediate or urgent care in case of
      perianaesthetic dental injury.

PMID- 22377416
TI  - Cellular-based modeling of oscillatory dynamics in brain networks.
AB  - Oscillatory, population activities have long been known to occur in our brains
      during different behavioral states. We know that many different cell types exist
      and that they contribute in distinct ways to the generation of these activities.
      I review recent papers that involve cellular-based models of brain networks, most
      of which include theta, gamma and sharp wave-ripple activities. To help organize
      the modeling work, I present it from a perspective of three different types of
      cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based
      modeling is taken to encompass the four features of experiment, model
      development, theory/analyses, and model usage/computation. The three modeling
      types are shown to include these features and interactions in different ways.

PMID- 22377419
TI  - Advances in collaborative evaluation.
AB  - Collaborative evaluation is an approach that offers, among others, many
      advantages in terms of access to information, quality of information gathered,
      opportunities for creative problem-solving, and receptivity to findings. In the
      last decade, collaborative evaluation has grown in popularity along with similar
      participatory, empowerment, and utilization-focused evaluation approaches.
      Increasingly, it has brought together evaluators and stakeholders from different
      sectors, disciplines, and cultures to exchange knowledge on how collaboration can
      be used as a strategic tool for fostering and strengthening evaluation practice.
      O'Sullivan (2004) and Rodriguez-Campos (2005, 2008) brought forward collaborative
      evaluation conceptual frameworks that distinguished it from other approaches.
      This article updates those conceptual frameworks and discusses key collaborative
      evaluation advances in order to further clarify and facilitate engagement in
      sound practice.

PMID- 22377421
TI  - Effects of dietary bovine lactoferrin on growth, physiological performance, iron
      metabolism and non-specific immune responses of Siberian sturgeon Acipenser
      baeri.
AB  - The present experiment was carried out to investigate the effects of different
      levels of dietary lactoferrin (LF) on growth performance, physiological status,
      iron absorption and innate immune response of juvenile Siberian sturgeon
      Acipenser baeri. Fish were fed with six different rations including 0, 100, 200,
      400, 800 and 1600 mg LF kg(-1) diet for 8 weeks. At the end of the experiment,
      samples were collected for estimating the physiological and immunological
      parameters. Dietary LF did not change the fish growth performance, hematological
      parameters, serum proteins or hepatic enzymes. Moreover, stress indicators
      (plasma cortisol, glucose and lactate) were not affected by dietary LF. The iron
      absorption of fish was considerably affected by LF; thus, plasma iron in LF
      treatments greatly declined and the total iron binding capacity (TIBC)
      significantly increased in fish fed with 800 mg LF kg(-1). In addition, the liver
      iron content markedly increased in some LF-treatments, but the variation of
      muscle iron concentration in treatments was insignificant. The amount of mucus
      secretion and serum bactericidal activity rose in fish fed on dietary LF,
      although other non-specific immune responses such as mucus bactericidal activity,
      serum and mucus lysozyme activity, serum peroxidase, serum natural hemolytic
      complement activity and serum IgM were not influenced by LF. This study revealed
      the ability of dietary LF to sequester iron, which is an essential nutrient
      required for the growth of bacteria. LF was also shown to improve some
      physiological and immunological parameters of Siberian sturgeon, to some extent.

PMID- 22377422
TI  - Bioinformatics and systems biology.
AB  - Delivering personalized therapeutic options to cancer patients based on the
      genetic and molecular aberrations of the tumor offers great promise to improve
      the outcomes of cancer therapy. Significant progress in biotechnology has allowed
      the measurement of tens of thousands of "omic" data points across multiple levels
      (DNA, RNA protein, metabolomics) from a single tumor biopsy sample in a
      reasonable time frame for making clinical decisions. With this data in hand, the
      challenge from the bioinformatics and systems biology point of view is how does
      one convert data into information and knowledge that can improve the delivery of
      personalized therapy to the patient.

PMID- 22377424
TI  - Understanding the association between maternal education and use of health
      services in Ghana: exploring the role of health knowledge.
AB  - This paper examines the role of health knowledge in the association between
      mothers' education and use of maternal and child health services in Ghana. The
      study uses data from a nationally representative sample of female respondents to
      the 2008 Ghana Demographic and Health Survey. Ordered probit regression models
      evaluate whether women's health knowledge helps to explain use of three specific
      maternal and child health services: antenatal care, giving birth with the
      supervision of a trained professional and complete child vaccination. The
      analyses reveal that mothers' years of formal education are strongly associated
      with health knowledge; health knowledge helps explain the association between
      maternal education and use of health services; and, net of a set of stringent
      demographic and socioeconomic controls, mothers' health knowledge is a key factor
      associated with use of health services.

PMID- 22377425
TI  - [Internet, SMS or voice portals tools. New technologies for an old problem].
AB  - OBJECTIVE: To analyse the frequency of use, effectiveness and usability of
      automated systems for obtaining appointments in primary care from a user point of
      view. METHODS: A cross-sectional study was conducted using a telephone survey of
      a random sample of 6193 patients (or parents or guardians of paediatric patients)
      treated in primary care in the Valencian Autonomous Community. RESULTS: A total
      of 397 (13.4%) adult patients and 1000 (31%) of parents or guardians of the
      paediatric patients used the Internet. The Voice Portal (225, 3.6%) and SMS (57,
      0.9%) was the least used. The Internet was mostly used by men (chi(2) 15.1,
      P<.004) and among adult patients aged between 51 and 70 years (chi(2) 40.5,
      P<.001). The traditional channels (telephone call or asking for an appointment
      personally) were used by chronic patients (chi(2) 28.7, P<.001) and those with
      who used the health sytem less (chi(2) 52, P<.001). The use of ICT is not
      responsible for delays in the date of appointment. Usability was very high (above
      90%), except in the case of the system based on SMS (80.7%). CONCLUSIONS: The
      Internet is the preferred channel among ICT to obtain an appointment. Its use is
      expected to increase. The effectiveness of ICT to get an appointment is somewhat
      higher than traditional channels. The usability of ICT to get an appointment is
      similar or superior to the traditional channels. The exception is the messages
      from a mobile.

PMID- 22377426
TI  - Pathogenic potential to humans of bovine Escherichia coli O26, Scotland.
AB  - Escherichia coli O26 and O157 have similar overall prevalences in cattle in
      Scotland, but in humans, Shiga toxin-producing E. coli O26 infections are fewer
      and clinically less severe than E. coli O157 infections. To investigate this
      discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland
      and continental Europe. The genetic background of some strains from Scotland was
      closely related to that of strains causing severe infections in Europe. Nonmetric
      multidimensional scaling found an association between hemolytic uremic syndrome
      (HUS) and multilocus sequence type 21 strains and confirmed the role of stx(2) in
      severe human disease. Although the prevalences of E. coli O26 and O157 on cattle
      farms in Scotland are equivalent, prevalence of more virulent strains is low,
      reducing human infection risk. However, new data on E. coli O26-associated HUS in
      humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli
      and for understanding stx(2) phage acquisition.

PMID- 22377428
TI  - The tolerance of Jatropha curcas seedlings to NaCl: an ecophysiological analysis.
AB  - Jatropha curcas L. is a biodiesel crop that is resistant to drought stress.
      However, the salt tolerance of this plant has not yet been studied. To address
      this question, J. curcas seedlings were grown in a fertilised substrate to
      evaluate the effects of salinity stress on growth, leaf water relation and
      organic solutes, leaf and root mineral concentrations, chlorophyll fluorescence
      parameters, and carbohydrate concentration. The experiment consisted of six
      treatments with different concentrations of NaCl in the irrigation water: 0
      (control), 30, 60, 90, 120 and 150 mM. The total biomass exhibited a salt-induced
      decrease in the 60 mM or higher NaCl concentrations. The Cl(r) concentration was
      higher than the Na(+) concentration in all of the plant tissues. The water
      potential and relative water content of the leaves were not affected by any of
      the salt treatments. However, salinity induced a decline in the leaf K(+)
      concentration, together with a significant enhancement in the leaf P, S, Fe, Zn,
      Mn and Cu levels. The net assimilation of CO2 also decreased with the salt
      treatment, due in part to non-stomatal limitation from the increase in C(a)/C(i)
      and a decrease in the maximum quantum efficiency (F(v)/F(m)) of photosystem II
      and soil plant analysis development (SPAD) units. This work suggests that J.
      curcas seedlings exhibit a moderate tolerance to salinity, as the plants were
      able to tolerate up to 4 dS m(-1) (EC water irrigation; 30 mM NaCl). The negative
      influences of salinity in this crop are mainly due to Cl(r) and/or Na(+) toxicity
      and to a nutritional imbalance caused by an increase in the Na(+)/K(+) ratio. The
      osmotic effect of salinity in this species is negligible, perhaps due to its
      strong control of leaf transpiration, which reduces water loss.

PMID- 22377429
TI  - Inhibitory effects of hypo-osmotic stress on extracellular carbonic anhydrase and
      photosynthetic efficiency of green alga Dunaliella salina possibly through
      reactive oxygen species formation.
AB  - In this study, Dunaliella salina (D. salina) maintained in 300/00 salinity for
      more than two years was exposed to the salinities of 50/00, 100/00, 200/00,
      300/00 (control) in order to investigate oxidative burst and it's possible
      connection with extracellular carbonic anhydrase (CA) under hypo-osmotic stress
      (low salinity). The results indicated that intracellular ROS contents increased
      significantly when cells were exposed to salinity of 5 and 100/00, and the
      increase also occurred at 200/00 salinity. The activity of extracellular CA and
      its gene (P60) expression decreased significantly when cells were exposed to
      salinity of 5-200/00. Data from H2O2 treatments hinted that ROS production was
      possibly one of the factors affecting CA, including enzyme activity and gene
      expression levels. Significant inhibition of effective quantum efficiency of PSII
      and photosynthetic oxygen evolution rate were observed with the increase of ROS
      production and decline of CA activities. Taken together, hypo-osmotic stresses
      could induce ROS production in D. salina, and CA enzyme activities and expression
      levels were consequently inhibited. As a result, algal photosynthesis and oxygen
      evolution were inhibited.

PMID- 22377431
TI  - Adaptive control reduces trip-induced forward gait instability among young
      adults.
AB  - A vital functional plasticity of humans is their ability to adapt to threats to
      posture stability. The purpose of this study was to investigate adaptation to
      repeated trips in walking. Sixteen young adults were recruited and exposed to the
      sudden (electronic-mechanical) release of an obstacle, 11-cm in height, in the
      path of over ground walking during the mid-to-late left swing phase. Although
      none of the subjects fell on the first of eight unannounced, consecutive trips,
      all of them had to rely on compensatory step with a step length significantly
      longer than their regular to reduce their instability. In the subsequent trials,
      they were able to rapidly make adaptive adjustments in the control of their
      center-of-mass (COM) stability both proactively and reactively (i.e., before and
      after hitting or crossing the obstacle), such that the need for taking
      compensatory step was substantially diminished. The proactive adaptations
      included a reduced forward COM velocity that lessened forward instability in mid
      to-late stance and an elevated toe clearance that reduced the likelihood of
      obstacle contact. The reactive adjustments were characterized by improved trunk
      control (by reducing its forward rotation) and limb support (by increasing hip
      height), and reduced forward instability (by both the posterior COM shift and the
      reduction in its forward velocity). These findings suggest that young adults can
      adapt appropriately to repeated trip perturbations and to reduce trip-induced
      excessive instability in both proactive and reactive manners.

PMID- 22377435
TI  - Splenectomy as a therapeutic approach in refractory hemophagocytic
      lymphohistiocytosis.
AB  - Zhang et al. have reported a case of an adult man with hemophagocytic
      lymphohistiocytosis (HLH) with an unknown etiology who has achieved a remission
      of HLH following comprehensive treatment based on splenectomy. In the present
      communication, the author critically discusses diagnostic and therapeutic issues
      related to the reported case, and questions utility of splenectomy in the
      treatment of active HLH.

PMID- 22377436
TI  - Antimicrobial drug resistance in Peru.

PMID- 22377437
TI  - Pain-related fear predicts reduced spinal motion following experimental back
      injury.
AB  - The current study examined the prospective relationship between pain-related fear
      and altered motor behavior, as well as perceived interference, among 51 healthy
      participants following induction of delayed-onset muscle soreness (DOMS) to the
      trunk extensor muscles. Healthy participants without history of back pain
      completed standardized reaches to high and low targets at self-paced and rapid
      speeds before and after induction of acute low back pain using a DOMS paradigm.
      Pain-related fear was assessed prior to DOMS induction. Three-dimensional joint
      motions of the thoracic spine, lumbar spine, and hip were recorded using an
      electromagnetic tracking device. DOMS-induced differences between high- and low
      fear participants were observed for lumbar spine flexion, but not for thoracic or
      hip flexion. Pain-related fear scores were not predictive of lumbar flexion
      during baseline, but predicted reduced lumbar flexion during self- and fast-paced
      trials to low target locations once DOMS was induced. Pain-related fear was
      likewise predictive of perceived interference in life activities following DOMS
      induction. The findings suggest that initially pain-free individuals with high
      pain-related fear adopt avoidant spinal strategies during common reaching
      movements shortly after injury is sustained, which may comprise a risk factor for
      future pain and disability.

PMID- 22377438
TI  - Do clinicians adhere to treatment recommendations for neuropathic pain?

PMID- 22377439
TI  - Chronic inflammatory pain is associated with increased excitability and
      hyperpolarization-activated current (Ih) in C- but not Adelta-nociceptors.
AB  - Inflammatory pain hypersensitivity results partly from hyperexcitability of
      nociceptive (damage-sensing) dorsal root ganglion (DRG) neurons innervating
      inflamed tissue. However, most of the evidence for this is derived from
      experiments using acute inflammatory states. Herein, we used several approaches
      to examine the impact of chronic or persistent inflammation on the excitability
      of nociceptive DRG neurons and on their expression of I(h) and the underlying
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which
      regulate neuronal excitability. Using in vivo intracellular recordings of somatic
      action potentials from L4/L5 DRG neurons in normal rats and rats with hindlimb
      inflammation induced by complete Freund's adjuvant (CFA), we demonstrate
      increased excitability of C- but not Adelta-nociceptors, 5 to 7 days after CFA.
      This included an afterdischarge response to noxious pinch, which may contribute
      to inflammatory mechanohyperalgesia, and increased incidence of spontaneous
      activity (SA) and decreased electrical thresholds, which are likely to contribute
      to spontaneous pain and nociceptor sensitization, respectively. We also show,
      using voltage clamp in vivo, immunohistochemistry and behavioral assays that (1)
      the inflammation-induced nociceptor hyperexcitability is associated, in C- but
      not Adelta-nociceptors, with increases in the mean I(h) amplitude/density and in
      the proportion of I(h) expressing neurons, (2) increased proportion of small DRG
      neurons (mainly IB4-negative) expressing HCN2 but not HCN1 or HCN3 channel
      protein, (3) increased HCN2- immunoreactivity in the spinal dorsal horn, and (4)
      attenuation of inflammatory mechanoallodynia with the selective I(h) antagonist,
      ZD7288. Taken together, the findings suggest that C- but not Adelta-nociceptors
      sustain chronic inflammatory pain and that I(h)/HCN2 channels contribute to
      inflammation-induced C-nociceptor hyperexcitability.

PMID- 22377442
TI  - Management of intractable epistaxis: endoscopy or nasal packing?
AB  - OBJECTIVES: To investigate common origins of intractable epistaxis, and the
      efficacy of endoscopic management. METHODS: Retrospective study of 265 patients
      with uncontrolled idiopathic epistaxis presenting between July 2008 and July
      2009. Patients underwent endoscopic examination and subsequent radiofrequency
      electrocautery, selective packing or observation. RESULTS: Nasal endoscopy
      indicated that the commonest bleeding sources were the superior nasal septum at
      the olfactory cleft (39.2 per cent), the inferior meatus (27.5 per cent), the
      sphenoethmoid recess (6.0 per cent), the middle meatus (5.3 per cent) and other
      locations (3.4 per cent). Bleeding was successfully controlled with nasal
      endoscopy plus radiofrequency electrocautery or selective packing. In 49 (18.5
      per cent) patients, no abnormality was identified; these patients received
      observation only, and no further bleeding occurred. None of the patients had
      serious complications or recurrent epistaxis during the three-month follow-up
      period. CONCLUSION: Thorough endoscopic examination combined with radiofrequency
      electrocautery should be used as first-line therapy for intractable epistaxis.

PMID- 22377443
TI  - Within-subject joint independent component analysis of simultaneous fMRI/ERP in
      an auditory oddball paradigm.
AB  - The integration of event-related potential (ERP) and functional magnetic
      resonance imaging (fMRI) can contribute to characterizing neural networks with
      high temporal and spatial resolution. This research aimed to determine the
      sensitivity and limitations of applying joint independent component analysis
      (jICA) within-subjects, for ERP and fMRI data collected simultaneously in a
      parametric auditory frequency oddball paradigm. In a group of 20 subjects, an
      increase in ERP peak amplitude ranging 1-8 MUV in the time window of the P300
      (350-700 ms), and a correlated increase in fMRI signal in a network of regions
      including the right superior temporal and supramarginal gyri, was observed with
      the increase in deviant frequency difference. JICA of the same ERP and fMRI group
      data revealed activity in a similar network, albeit with stronger amplitude and
      larger extent. In addition, activity in the left pre- and post-central gyri,
      likely associated with right hand somato-motor response, was observed only with
      the jICA approach. Within-subject, the jICA approach revealed significantly
      stronger and more extensive activity in the brain regions associated with the
      auditory P300 than the P300 linear regression analysis. The results suggest that
      with the incorporation of spatial and temporal information from both imaging
      modalities, jICA may be a more sensitive method for extracting common sources of
      activity between ERP and fMRI.

PMID- 22377444
TI  - Reconstruction of the decision-making process in assessing musculoskeletal chest
      pain: an exploratory study using recursive partitioning.
AB  - OBJECTIVE: The purposes of this study were to identify the most important
      determinants from the patient history and clinical examination in diagnosing
      musculoskeletal chest pain (MSCP) in patients with acute noncardiac chest pain
      when supported by a structured protocol and to construct a decision tree for
      identification of MSCP in acute noncardiac chest pain. METHODS: Consecutive
      patients with noncardiac chest pain (n = 302) recruited from an emergency
      cardiology department were assessed. Using data from self-report questionnaires,
      interviews, and clinical assessment, patient characteristics were associated with
      the MSCP diagnosis, and the decision-making process of the clinician was
      reconstructed using recursive procedures in the tradition of constructing
      Classification and Regression Trees. RESULTS: Thirty-eight percent of patients
      had MSCP. There was no single determinant that predicted the condition
      completely. However, many items with high associations could be identified,
      mainly with high negative predictive value. The decision-making process was
      reconstructed giving rise to a 5-step, linear decision tree without branches.
      CONCLUSIONS: Clinicians use a combination of indicators including systematic
      palpation of the spine and chest wall and items from the case history to diagnose
      MSCP. However, the high negative predictive values of the main determinants
      suggest that the MSCP diagnosis may be a diagnosis by exclusion.

PMID- 22377446
TI  - [Deep venous thrombosis in a case of acute staphylococcal osteomyelitis].

PMID- 22377447
TI  - Cryptosporidium spp. in quails (Coturnix coturnix japonica) in Henan, China:
      molecular characterization and public health significance.
AB  - The prevalence of Cryptosporidium spp. was investigated in scale quail (Coturnix
      coturnix japonica) farms in Henan Province, China between September 2006 and
      August 2007. One thousand eight hundred and eighteen fecal samples from 47 quail
      farms in five areas were collected for the examination of Cryptosporidium
      oocysts. The overall prevalence of Cryptosporidium was 13.1% (95% CI 13.1+/-1.6%)
      (29 of 47 farms), with 72-100-day-old quails having the highest prevalence
      (23.6%, 95% CI 23.6+/-2.6%) (chi(2)=64.91; rho<0.01). The highest prevalence was
      observed in autumn (21.8%, 95% CI 21.8+/-3.1%) and the lowest in winter
      (chi(2)=74.83; rho<0.01). Two hundred and thirty-nine Cryptosporidium-positive
      samples were analyzed by PCR-restriction fragment length polymorphism (RFLP)
      analysis of the small subunit (SSU) rRNA gene, and 42 were further analyzed by
      DNA sequencing of the PCR products. Two Cryptosporidium species were identified,
      Cryptosporidium baileyi in 237 birds on 29 farms, and potentially zoonotic
      Cryptosporidium meleagridis in only two birds on two farms. These findings may
      suggest that quails are not a major source of zoonotic Cryptosporidium in the
      study area.

PMID- 22377448
TI  - Fatal measles without rash in immunocompetent adult, France.

PMID- 22377445
TI  - [Evaluation of anthropometric development in patients with enuresis].
AB  - INTRODUCTION: An epidemiological study was conducted to assess the anthropometric
      development in children diagnosed with primary monosymptomatic nocturnal
      enuresis, depending on the treatment option selected. PATIENTS AND METHODS: A
      longitudinal series of cases including 548 children aged 5-10 years.
      Anthropometric parameters of children were assessed at diagnosis, and after one
      and two years of treatment. RESULTS: Children with primary monosymptomatic
      nocturnal enuresis showed no anthropometric changes when their data were compared
      to the standard deviation score of height, weight, and body mass index (BMI).
      Overall, no changes were seen in the above mentioned parameters after two years
      of treatment for enuresis (except for a weight standard deviation score (SDS)
      decrease in boys). We only found a decrease in the size and weight in those
      children undergoing behavioral therapy with or without an alarm, findings that,
      given the limitations of the study, were not considered significant. The odds
      ratio for cure after one and two years of treatment was 1.41 (95% CI: 0.85-2.34)
      and 1.52 (95% CI: 0.86-2.70) for desmopressin (and watchful waiting) as compared
      to all other options. CONCLUSIONS: In this study, children had SDS values of
      height, weight, and BMI similar to healthy children of the same age and sex
      before and after treatment for primary monosymptomatic nocturnal enuresis.
      Desmopressin appeared to increase the probability of cure after one and two years
      of treatment, however these data should be corroborated in future randomized
      clinical trials.

PMID- 22377449
TI  - Lineage-specific virulence determinants of Haemophilus influenzae biogroup
      aegyptius.
AB  - An emergent clone of Haemophilus influenzae biogroup aegyptius (Hae) is
      responsible for outbreaks of Brazilian purpuric fever (BPF). First recorded in
      Brazil in 1984, the so-called BPF clone of Hae caused a fulminant disease that
      started with conjunctivitis but developed into septicemic shock; mortality rates
      were as high as 70%. To identify virulence determinants, we conducted a pan
      genomic analysis. Sequencing of the genomes of the BPF clone strain F3031 and a
      noninvasive conjunctivitis strain, F3047, and comparison of these sequences with
      5 other complete H. influenzae genomes showed that >77% of the F3031 genome is
      shared among all H. influenzae strains. Delineation of the Hae accessory genome
      enabled characterization of 163 predicted protein-coding genes; identified
      differences in established autotransporter adhesins; and revealed a suite of
      novel adhesins unique to Hae, including novel trimeric autotransporter adhesins
      and 4 new fimbrial operons. These novel adhesins might play a critical role in
      host-pathogen interactions.

PMID- 22377450
TI  - Reactive arthritis after the intravesical instillation of BCG.
AB  - The intravesical instilation of bacillus Calmette-Guerin (BCG) is a widely used
      and efficacious procedure for treatment of intermediate to high-grade superficial
      bladder cancer. The occurrence of osteoarticular side effects is infrequent
      compared to the number of administrated doses, and reactive arthritis is included
      within these effects. We present the case of a 54 years old HLA-27 (+) male, who
      developed reactive arthritis featuring asymmetric olygoarthritis and dactylitis
      after the second intravesical BCG instillation, which was resolved with
      administration of Etoricoxib and Isoniazid.

PMID- 22377451
TI  - Self-reported quality of life ratings of people with dementia: the role of
      attitudes to aging.
AB  - BACKGROUND: Attitudes to aging have not previously been assessed in people with
      dementia. The possession of positive life attitudes into older age has the
      potential to induce resilience to health changes and may explain the discrepancy
      between self-reported and proxy ratings of quality of life (QoL). The aim of this
      study was to explore the attitudes of people with dementia to determine the main
      factors that predict these attitudes and any relationship that exists with self
      reported QoL. METHODS: Fifty-six participants with dementia were recruited from a
      memory clinic setting. The Bath Assessment of Subjective Quality of Life in
      Dementia, Attitudes to Aging Questionnaire (AAQ), Memory Functioning Scale,
      Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and
      Mini-Mental State Examination were administered. The AAQ was also completed by 86
      community-dwelling older adults without dementia. RESULTS: Participants with
      dementia displayed a significantly stronger endorsement of the negative attitude
      that aging is a time of psychosocial loss than those without dementia. Regression
      analyses suggest this negative attitude acts as a partial mediator in the
      relationship between the person's level of insight and self-reported QoL.
      CONCLUSIONS: Negative attitudes to aging had a direct impact on the self-reported
      QoL ratings of people with dementia. The view of aging as a time of psychosocial
      loss was most significant for people with dementia and suggests that negative
      stereotypes of dementia need to be challenged. In order to promote QoL, care
      should focus on abilities that the person retains rather than what has been lost.

PMID- 22377453
TI  - Impact of culture medium on maturation of bone marrow-derived murine dendritic
      cells via the aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) plays a role in modulating dendritic cell
      (DC) immunity. Iscove's modified Dulbecco's medium (IMDM) contains higher amounts
      of AhR ligands than RPMI1640 medium. Here, we examined the influence of AhR
      ligand-containing medium on the maturation and T-cell stimulatory capacity of
      bone marrow-derived murine dendritic cells (BMDCs). BMDCs generated in IMDM
      (BMDCs/IMDM) expressed higher levels of co-stimulatory and MHC class II
      molecules, and lower levels of pattern-recognition receptors, especially toll
      like receptor (TLR) 2, TLR4, and scavenger receptor class A (SR-A), compared to
      BMDCs generated in RPMI1640 medium (BMDCs/RPMI). Cytokine responses against
      ligands of TLRs and antigen uptake mediated by SR-A were remarkably reduced in
      BMDCs/IMDM, whereas the T-cell stimulatory capacity of the cells was enhanced,
      compared to BMDCs/RPMI. The enhanced maturation of BMDCs/IMDM was attenuated in
      the presence of an AhR antagonist, indicating involvement of AhR in the
      maturation. Interestingly, BMDCs/IMDM induced Th2 and Th17 differentiation at low
      and high concentrations of antigen respectively, when co-cultured with CD4(+) T
      cells from antigen-specific T-cell receptor transgenic mice. In contrast,
      BMDCs/RPMI induced Th1 differentiation predominantly in the co-culture. Taken
      together, optimal selection of medium seems necessary when studying BMDCs,
      depending on the target receptors on the cell surface of DCs and type of helper T
      cells for the co-culture.

PMID- 22377454
TI  - Luteolin downregulates TLR4, TLR5, NF-kappaB and p-p38MAPK expression,
      upregulates the p-ERK expression, and protects rat brains against focal ischemia.
AB  - BACKGROUND: Inflammatory damage is known to be involved in ischemic stroke.
      Luteolin has been proved to elicit a series of biologic effects through its anti
      inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether
      this protective effect applies to ischemic injury in brain is still unknown, we
      therefore investigate the potential neuroprotective role of luteolin in ischemic
      stroke and the underlying mechanisms. METHODS: Male Sprague-Dawley rats were
      subjected to pMCAO and luteolin was administered intraperitoneally immediately
      after surgery, then once daily thereafter. Neurological deficit, infarct volume,
      and brain water content were measured at 24 h and 72 h after stroke. The
      expression of TLR4, TLR5, and NF-kappaB were measured by real-time PCR,
      immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular
      signal-regulated kinase (ERK) were detected by IHC, and Western blot. RESULTS:
      Compared with pMCAO group, luteolin significantly alleviated neurological
      deficit, decreased infarct volume and suppressed edema after ischemic stroke,
      which were accompanied with decreased expression of TLR4, TLR5, NF-kappaB and p
      p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05).
      CONCLUSIONS: Luteolin protected the brain from the damage caused by pMCAO, and
      this effect may be through downregulation of TLR4, TLR5, NF-kappaB, p38MAPK and
      upregulation of ERK expression.

PMID- 22377455
TI  - Effect of electrical stimulation of sciatic nerve on synaptic plasticity of
      spinal dorsal horn and spinal c-fos expression in neonatal, juvenile and adult
      rats.
AB  - To explore the response to nociceptive stimuli in spinal cord of immature rat and
      observe the electrical stimulation of the sciatic nerve on synaptic plasticity of
      the spinal dorsal horn and spinal c-fos expression in rats of different ages, MK
      801 was added to the spinal cord of rats, and the resulting changes in field
      potential as well as c-fos expression were recorded. LTP in neonatal rats was
      mainly evoked by A-type nerve fibers, whereas LTP in juvenile and adult rats was
      mainly evoked by C-type nerve fibers. C-fos expression was significantly
      increased in the superficial and deep layers of the spinal dorsal horn and in the
      ventral horn in neonatal rats indicating that the pain signal changed with age.

PMID- 22377456
TI  - [Fournier's gangrene].

PMID- 22377457
TI  - [Calcific tendinitis of the shoulder and compensation consequences: calcific
      disorder of tendon or tendinopathy with calcification?].

PMID- 22377458
TI  - [Anatomofunctional correlates of delusional parasitosis].

PMID- 22377459
TI  - [Importance of patient's choice in the treatment of erectile dysfunction].
AB  - Erectile dysfunction (ED) affects nearly one out of two men over age 45. ED is
      known to alter the quality of life of patients, and to affect significantly their
      sexual life and relations, as well as those of their female partners.
      Phosphodiesterase 5 inhibitors (PDE5) inhibitors currently represent the
      reference treatment for ED, because of their efficacy and good tolerability. The
      presence of erectile disorders capable of altering considerably the life of a
      couple makes it necessary to find ways for patients and their partners to get
      more involved in the treatment choices. A "customized" solution responding to
      patient's needs and resulting from a decision shared with the patient and his
      partner will allow a better compliance and efficacy of the treatment.

PMID- 22377460
TI  - [Metformin associates lactic acidosis].
AB  - Metformin Associates lactic acidosis (MALA) is a metabolic acidosis with higher
      anion gap, high levels of blood lactates and treatment by metformin. MALA is a
      very rare entity but is associated with high mortality (30 to 50%). The
      extrarenal blood purification may be necessary in emergency. Relatively good
      clinical tolerance contrasts with a very elevated serum lactate. There is always
      a trigger and hypovolemia is prevalent. MALA often occurs when its prescription
      is not indicated (renal failure, cardiac failure, hypovolemia, or patient aged
      over 80 years). Metformin must be stopped in situations of acute hypovolemia or
      frail patients as diuretics or blockers of the rennin-angiotensin-aldosterone
      system.

PMID- 22377461
TI  - [Eye and corticosteroid's use].
AB  - Most common side effects of systemic corticosteroids are posterior subcapsular
      cataract and glaucoma. There is no way to prevent corticosteroid-induced
      cataract. The risk of these complications varies (cataract 11 to 15%; glaucoma
      12.8%), and it depends on the dose, duration of administration and terrain. The
      discontinuation of corticosteroid therapy is required in cases of uncontrolled
      glaucoma by hypotonic treatment. Long-term topical or general steroids
      prescription has to be done after an ophthalmological examination. Indications of
      ophthalmic general corticosteroids are acute orbital and ocular inflammations.
      affecting the middle and posterior segments of the eye, or sclera when topical
      treatment is ineffective. When administered topically, only 5% of the delivered
      dose is absorbed by the anterior segment, distribution is almost zero in the
      middle and posterior segments of the eye.

PMID- 22377462
TI  - [How I do... a cesarean section in an obese patient?].

PMID- 22377469
TI  - Separation and quantification of 15 carotenoids by reversed phase high
      performance liquid chromatography coupled to diode array detection with
      isosbestic wavelength approach.
AB  - The manuscript presents the development of a new reverse phase high performance
      liquid chromatography (RP-HPLC) photo diode array detection method allowing the
      separation and quantification of 15 carotenoids (adonirubin, adonixanthin,
      astaxanthin, astaxanthin dimethyl disuccinate, asteroidenone, beta-apo-8'
      carotenal, beta-apo-8'-carotenoic acid ethyl ester, beta-carotene, canthaxanthin,
      capsanthin, citranaxanthin, echinenone, lutein, lycopene, and zeaxanthin), 10 of
      which are feed additives authorised within the European Union. The developed
      method allows for the reliable determination of the total carotenoid content in
      one run using the corresponding E-isomer as calibration standard while taking
      into account the E/Z-isomers composition. This is a key criterion for the
      application of the method, since for most of the analytes included in this study
      analytical standards are only available for the E-isomers. This goal was achieved
      by applying the isosbestic concept, in order to identify specific wavelengths, at
      which the absorption coefficients are identical for all stereoisomers concerned.
      The second target referred to the optimisation of the LC conditions. By means of
      an experimental design, an optimised RP-HPLC method was developed allowing for a
      sufficient chromatographic separation of all carotenoids. The selected method
      uses a Suplex pKb-100 HPLC column and applying a gradient with a mixture of
      acetonitrile, tert-butyl-methyl ether and water as mobile phases. The limits of
      detection and limits of quantification ranged from 0.06 mg L(-1) to 0.14 mg L(-1)
      and from 0.20 mg L(-1) to 0.48 mg L(-1), respectively.

PMID- 22377470
TI  - Determination of pharmaceutically related compounds by suppressed ion
      chromatography: III. Role of electrolytic suppressor design.
AB  - For the hyphenation of ion chromatography to nebulising detectors or mass
      spectrometry, suppression of the non-volatile ionic eluent to water is a required
      step to avoid elevated detector baselines. Presented here is a study of three new
      designs of electrolytic suppressors, incorporating high ion-exchange capacity
      screens and high ion-exchange capacity membranes in different thickness and
      compositions. These designs aim to minimise hydrophobic interactions of the
      suppressor with organic analytes and to provide higher compatibility with eluents
      containing acetonitrile. In comparison with a commercially available electrolytic
      suppressor and also a commercially available chemical suppressor, the new high
      capacity suppressor showed superior performance, exhibiting minimal interactions
      with a test set of analytes under the examined conditions. This led to the
      attainment of high recoveries of the analytes after suppression (93-99% recovery)
      and significantly reduced band broadening during suppression. The new suppressor
      has been shown to perform well under both isocratic and gradient elution
      conditions.

PMID- 22377472
TI  - [Treatment adherence and persistence in patients with chronic hepatitis B virus
      infection].

PMID- 22377473
TI  - Using genotyping and geospatial scanning to estimate recent mycobacterium
      tuberculosis transmission, United States.
AB  - To determine the proportion of reported tuberculosis (TB) cases due to recent
      transmission in the United States, we conducted a cross-sectional study to
      examine culture-positive TB cases with complete genotype results (spoligotyping
      and 12-locus mycobacterial interspersed repetitive unit-variable-number tandem
      repeat typing) reported during January 2005-December 2009. Recently transmitted
      cases were defined as cases with matching results reported within statistically
      significant geospatial zones (identified by a spatial span statistic within a
      sliding 3-year window). Approximately 1 in 4 TB cases reported in the United
      States may be attributed to recent transmission. Groups at greatest risk for
      recent transmission appear to be men, persons born in the United States, members
      of a minority race or ethnic group, persons who abuse substances, and the
      homeless. Understanding transmission dynamics and establishing strategies for
      rapidly detecting recent transmission among these populations are essential for
      TB elimination in the United States.

PMID- 22377475
TI  - Steam refining as an alternative to steam explosion.
AB  - In steam pretreatment the defibration is usually achieved by an explosion at the
      end of the treatment, but can also be carried out in a subsequent refiner step. A
      steam explosion and a steam refining unit were compared by using the same raw
      material and pretreatment conditions, i.e. temperature and time. Smaller particle
      size was needed for the steam explosion unit to obtain homogenous slurries
      without considerable amounts of solid chips. A higher amount of volatiles could
      be condensed from the vapour phase after steam refining. The results from
      enzymatic hydrolysis showed no significant differences. It could be shown that,
      beside the chemical changes in the cell wall, the decrease of the particle size
      is the decisive factor to enhance the enzymatic accessibility while the explosion
      effect is not required.

PMID- 22377476
TI  - A new marine bacterial laccase with chloride-enhancing, alkaline-dependent
      activity and dye decolorization ability.
AB  - A bacterial laccase gene designated as lac21 was screened from a marine microbial
      metagenomic library of the South China Sea based on sequence screening strategy.
      The protein encoded by lac21 shared less than 40% sequence identities with all of
      the laccases found. Lac21, which was recombinantly expressed in Escherichia coli,
      showed high activity toward syringaldazine at an optimum pH of 7.5 and
      temperature of 45 degrees C. Lac21 was stable at pH values ranging from 5.5 to
      9.0 and temperatures lower than 40 degrees C. Interestingly, chloride enhanced
      the laccase activity, with concomitant increase in substrate affinity.
      Furthermore, Lac21 has high decolorization capability toward azo dyes in the
      absence of redox mediators, with 80% of Reactive Deep Blue M-2GE (50mg/L) being
      decolorized by 15U/L enzyme after 24h incubation at 20 degrees C. These unusual
      properties demonstrate that the new bacterial laccase Lac21 has potentials in
      specific industrial or environmental applications.

PMID- 22377477
TI  - Fungal strain and incubation period affect chemical composition and nutrient
      availability of wheat straw for rumen fermentation.
AB  - Eleven white-rot fungi were examined for their potency to degrade lignin and to
      improve the rumen fermentability of wheat straw. The straw was inoculated with
      the fungi and incubated under solid state conditions at 24 degrees C for 0-49
      days to determine changes in in vitro gas production and chemical composition.
      Results show that some fungi could degrade lignin by as much as 63%, yet the
      delignification was highly correlated with the degradation of hemicellulose
      (r=0.96). Reduction in lignin was poorly (r=0.47), but the ratio between lignin
      and cellulose loss was strongly (r=0.87) correlated with the increase in gas
      production. Treatment with Ceriporiopsis subvermispora for 49 days increased
      total gas production of the straw from 200 to 309 ml/g organic matter (OM). It
      was concluded that some fungi highly selective for lignin and not for cellulose
      are able to improve the nutritive value of wheat straw as a ruminant feed.

PMID- 22377478
TI  - Chemical and biochemical characterisation of biochar-blended composts prepared
      from poultry manure.
AB  - The aim of this study was to assess the effect of a 2% (v/v) addition of biochar
      on the quality of a composting mixture prepared with poultry manure and different
      local organic wastes (rice husk and apple pomace). Compost quality was evaluated
      in terms of typical stabilisation indices, the microbial biomass and selected
      enzymatic activities related to the C, N and P cycles. The main effects of
      biochar were a 10% increase in C captured by humic substance extraction and a 30%
      decrease of water-soluble C, due to an enhanced degradation rate and/or the
      sorption of these labile compounds into the biochar. The urease, phosphatase and
      polyphenol oxidase activities of the biochar-blended compost were enhanced by 30
      40% despite the lower amount of microbial biomass. Denaturing gradient gel
      electrophoresis revealed a higher diversity of fungi in biochar-amended compost,
      suggesting a change in microbial composition compared to the unamended compost.

PMID- 22377480
TI  - Carbapenemase-producing Acinetobacter spp. in Cattle, France.

PMID- 22377482
TI  - Uterine inversion in association with uterine sarcoma: a case report with MRI
      findings and review of the literature.
AB  - Non-puerperal uterine inversion due to uterine sarcomas represents a very rare
      event with no reliable estimate of frequency in the literature. Clinically, the
      diagnosis of inversion may be difficult, as far as imaging procedures are
      concerned, although ultrasonography may prove to be useful. However, some
      characteristics such as the indentation of the fundic area and a depressed
      longitudinal groove extending from the uterus to the center of the inverted
      portion are difficult to recognize. Moreover, there is no specific computed
      tomography feature accurate enough to aid in the differential diagnosis. Here, we
      report a case of uterine inversion due to Mullerian uterine adenosarcoma whose
      preoperative workup and diagnosis took advantage of the application of magnetic
      resonance imaging.

PMID- 22377481
TI  - CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a
      Portuguese center.
AB  - BACKGROUND: Clopidogrel requires oxidation dependent on the cytochrome P450
      enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of
      function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to
      clopidogrel is well recognized. OBJECTIVE: To investigate the prevalence and
      prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome
      (ACS) population. METHODS: We performed a prospective, longitudinal study of 95
      patients admitted for an ACS between March and October 2009 to a single coronary
      care unit. Patients aged under 75 who survived hospital stay and for whom
      clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped
      using a commercially available kit. Patients were divided into two groups: Group
      A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers,
      slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a
      combined outcome of cardiovascular death, non-fatal myocardial infarction or re
      admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days.
      RESULTS: The median age of the population was 62.0 (51.0-68.0) years, and 83.2%
      were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no
      differences between the groups with respect to demographic data or history of
      cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and
      renal function were also similar. The groups were also homogenous with respect to
      GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical
      treatment and percutaneous revascularization during hospital stay. Event-free
      survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three
      readmissions for MI were documented, all in the slow metabolizers group.
      CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term
      prognostic marker.

PMID- 22377483
TI  - Climatic conditions and the onset of primary spontaneous pneumothorax: an
      investigation of the influence of solar terms.
AB  - OBJECTIVE: To study the correlation between climatic changes and the development
      of primary spontaneous pneumothorax (PSP). SUBJECTS AND METHODS: We
      retrospectively studied the relationship between 337 patients with conservatively
      treated PSP and meteorological conditions during a 3-year period in the urban
      area of Xi'an, China. The comparison was made depending on solar terms and on
      different aspects of atmospheric pressure, outdoor temperature, relative
      humidity, and wind speed. RESULTS: Significant differences were found between PSP
      and non-PSP days depending on daily mean values of outdoor temperature and
      atmospheric pressure (p = 0.001 and p < 0.001, respectively). However, no obvious
      differences of meteorological factor variations between the 'PSP day' and the
      'pre-PSP day' on days with and without PSP were found. The occurrence of PSP was
      associated with the solar terms Spring Equinox (p < 0.05) and End of Heat (p <
      0.01). CONCLUSION: Among the factors examined in our study, daily mean outdoor
      temperature and atmospheric pressure showed a strong correlation with the
      occurrence of PSP. The solar terms Spring Equinox and End of Heat were found to
      be closely related with PSP development, which shed light on a new way for PSP
      incidence evaluation.

PMID- 22377484
TI  - Strict glycaemic control improves skin microcirculation in patients with type 2
      diabetes: a report from the Diabetes mellitus And Diastolic Dysfunction (DADD)
      study.
AB  - BACKGROUND: Microcirculatory and endothelial dysfunction are signs of
      cardiovascular engagement in patients with type 2 diabetes. This study tested
      whether glucose normalisation may reverse this. METHODS: Thirty-nine T2DM
      patients (age 61+/-7 years, 58% females) with signs of mild diastolic dysfunction
      were randomised to strict glucose control based on insulin (I-group; n=21) or
      oral agents (O-group; n=18) for four months. Skin microcirculation was studied
      with laser Doppler fluxmetry and endothelial function with brachial artery flow
      mediated dilatation. RESULTS: Glucose control improved (reduction of HbA(1c) I
      group = -0.5%; O-group -0.7%; p=0.69). Microcirculation improved in the entire
      group (n=39) determined by foot laser Doppler fluxmetry (32.2+/-13.6 vs. 35.3+/
      13.1 perfusion units; p<0.001) and laser Doppler fluxmetry following heating
      (68.8+/-34.0 vs. 69.3+/-25.1 PU; p=0.007). Improvement was more consistent with
      oral agents than insulin. Endothelial function expressed as flow-mediated
      dilatation decreased in the I-group (6.0+/-2.2 to 4.7+/-3.0%; p=0.037) but
      remained unchanged in the O-group (4.8+/-2.3 to 5.0+/-3.7%; n.s.). CONCLUSIONS:
      Glycaemic normalisation improved skin microcirculation but not endothelial
      function in patients with type 2 diabetes with mild cardiovascular engagement.

PMID- 22377485
TI  - Global cardiovascular disease risk assessment in United States adults with
      diabetes.
AB  - BACKGROUND: Diabetes mellitus (DM) is often considered a risk equivalent for
      cardiovascular disease (CVD); however, the variation in CVD risk in adults with
      DM has not been described. METHODS: We studied 1114 US adults aged >=18 years
      with DM from national survey data and the proportion at low (<10%), intermediate
      (10-20%) and high (>20%) risk, or with CVD, by age, gender, ethnicity and
      diabetes type and treatment, and glycaemic and risk factor control by risk group.
      RESULTS: Overall, 22.9% were low, 17.5% intermediate, 31.4% high risk and 28.2%
      had pre-existing CVD (total 59.6% high risk/CVD). More Hispanics (32.4%) and
      Blacks (30.6%) versus Whites (18.8%) were at lower risk (p<0.0001). Among type 1
      versus 2 DM, 35% vs. 65% (p<0.0001) and among insulin users 68.1% were high risk
      or with CVD. However, among low-intermediate risk, >50% have metabolic syndrome
      and 7% chronic kidney disease, increasing the high risk/CVD group to 86.8%.
      Simultaneous achievement of HbA1c, blood pressure and low density lipoprotein
      cholesterol goals was low (<15%) regardless of risk group. CONCLUSIONS: Many DM
      patients are not at high 10-year CVD risk, but metabolic factors may place them
      at greater long-term risk. Risk assessment could help target the intensity of
      treatment.

PMID- 22377486
TI  - Seizures and X-linked intellectual disability.
AB  - Intellectual disability occurs as an isolated X-linked trait and as a component
      of recognizable X-linked syndromes in the company of somatic, metabolic,
      neuromuscular, or behavioral abnormalities. Seizures accompany intellectual
      disability in almost half of these X-linked disorders. The spectrum of seizures
      found in the X-linked intellectual disability syndromes is broad, varying in time
      of onset, type of seizure, and response to anticonvulsant therapy. The majority
      of the genes associated with XLID and seizures have now been identified.

PMID- 22377488
TI  - Aggregation behavior of aqueous dioctadecyldimethylammonium bromide/monoolein
      mixtures: a multitechnique investigation on the influence of composition and
      temperature.
AB  - A recently described non-viral gene delivery system [dioctadecyldimethylammonium
      bromide (DODAB)/monoolein (MO)] has been studied in detail to improve knowledge
      on the interactions between lamellar (DODAB) and non-lamellar-forming (MO)
      lipids, as a means to enhance their final cell transfection efficiency. Indeed,
      the morphology, fluidity, and size of these cationic surfactant/neutral lipid
      mixtures play an important role in the ability of these systems to complex
      nucleic acids. The different techniques used in this work, namely dynamic light
      scattering (DLS), fluorescence spectroscopy, differential scanning calorimetry
      (DSC), cryogenic transmission electron microscopy (cryo-TEM), light microscopy
      (LM), and surface pressure-area isotherms, allowed fully characterization of the
      phase behavior and aggregate morphology of DODAB/MO mixtures at different molar
      ratios. Overall, the results indicate that the final morphology of DODAB/MO
      aggregates depends on the balance between the tendency of DODAB to form zero
      curvature bilayer structures and the propensity of MO to form non-bilayer
      structures with negative curvature. These results also show that in the MO-rich
      region, an increase in temperature has a similar effect on aggregate morphology
      as an increase in MO concentration.

PMID- 22377489
TI  - Supra-long chain surfactants with double or triple quaternary ammonium
      headgroups.
AB  - Novel supra-long chain surfactants with double or triple quaternary ammonium
      salts (C(n)-2Am, C(n)-3Am, in which n represents a hydrocarbon chain length of
      18, 20, and 22) were synthesized, and electrical conductivity and surface tension
      were used to characterize their properties depending on both the hydrocarbon
      chain length and number of hydrophilic groups. The Krafft temperatures decreased
      remarkably with an increase in the quaternary ammonium headgroups, resulting in a
      high solubility in water. The critical micelle concentration (cmc) increased with
      an increase in the number of quaternary ammonium moieties in the hydrophilic
      group, and the difference in the cmc was smaller for C(n)-2Am and C(n)-3Am than
      for C(n)-2Am and C(n)-Am of alkyltrimethylammonium bromide. The surface tension
      at the cmc was approximately 45 and 48 mN m(-1) for C(n)-2Am and C(n)-3Am with
      n=18-22, respectively. This indicated that the supra-long chain surfactants could
      not efficiently adsorb at the air/water interface and orient by themselves, as is
      known for conventional surfactants.

PMID- 22377490
TI  - Surface speciation of Eu3+ adsorbed on kaolinite by time-resolved laser
      fluorescence spectroscopy (TRLFS) and parallel factor analysis (PARAFAC).
AB  - Time-resolved laser fluorescence spectroscopy (TRLFS) is an effective speciation
      technique for fluorescent metal ions and can be further extended by the parallel
      factor analysis (PARAFAC). The adsorption of Eu(3+) on kaolinite as well as
      gibbsite as a reference mineral was investigated by TRLFS together with batch
      adsorption measurements. The PAFAFAC modeling provided the fluorescence spectra,
      decay lifetimes, and relative intensity profiles of three Eu(3+) surface
      complexes with kaolinite; an outer-sphere (factor A) complex and two inner-sphere
      (factors B and C) complexes. Their intensity profiles qualitatively explained the
      measured adsorption of Eu(3+). Based on the TRLFS results in varied H(2)O/D(2)O
      media, it was shown that the outer-sphere complex exhibited more rapid
      fluorescence decay than Eu(3+) aquo ion, because of the energy transfer to the
      surface. Factor B was an inner-sphere complex, which became dominant at
      relatively high pH, high salt concentration and low Eu(3+) concentration. Its
      spectrum and lifetime were similar to those of Eu(3+) adsorbed on gibbsite,
      suggesting its occurrence on the edge face of the gibbsite layer of kaolinite.
      From the comparison with the spectra and lifetimes of crystalline or aqueous
      Eu(OH)(3), factor C was considered as a poly-nuclear surface complex of Eu(3+)
      formed at relatively high Eu(3+) concentration.

PMID- 22377491
TI  - Aedes albopictus mosquitoes, Yucatan Peninsula, Mexico.

PMID- 22377492
TI  - Elevated cerebrospinal fluid adenosine deaminase levels in patients with
      meningitis caused by varicella-zoster virus.

PMID- 22377493
TI  - [A skin lesion of rare origin].

PMID- 22377494
TI  - [Diseases associated with bloodstream infections caused by the new species
      included in the old Streptococcus bovis group].
AB  - OBJECTIVE: We sought to identify possible diseases associated with bloodstream
      infections caused by new species of S. bovis group isolated in blood cultures and
      by studying patient records METHODS: Forty-four consecutive blood culture
      isolates initially designated S. bovis were further characterised using
      phenotypic methods Patient records were examined. RESULTS: We identified 15
      Streptococcus gallolyticus subsp. gallolyticus, 24 Streptococcus gallolyticus
      subsp. pasteurianus, and 5 Streptococcus infantarius isolates in 44 BSI episodes.
      CONCLUSIONS: The association between S. bovis bacteraemia and endocarditis and/or
      colon carcinoma is highly dependent on the causative species. Streptococcus
      gallolyticus subsp. gallolyticus is a surrogate for endocarditis and/or bowel
      disease, whereas Streptococcus gallolyticus subsp. pasteurianus is a surrogate
      for hepato-biliary disease.

PMID- 22377495
TI  - Differences in the use of health resources by Spanish and immigrant HIV-infected
      patients.
AB  - BACKGROUND: HIV-immigrant use of health services and related cost has hardly been
      analysed. We compared resource utilisation patterns and direct health care costs
      between Spanish and immigrant HIV-infected patients. METHODS: All HIV-infected
      adult patients treated during the years 2003-2005 (372 patients) in this hospital
      were included. We evaluated the number of out-patient, Emergency Room (ER) and
      Day-care Unit visits, and number and length of admissions. Direct costs were
      analysed. We compared all variables between immigrant and Spanish patients.
      RESULTS: Immigrants represented 12% (n=43) of the cohort. There were no
      differences in the number of out-patient, ER, and day-care hospital visits per
      patient between both groups. The number of hospital admissions per patient for
      any cause was higher in immigrant than in Spanish patients, 1.3 (4.4) versus 0.9
      (2.7), P=.034. A high proportion of visits, both for the immigrant (45.1%) and
      Spanish patients (43.0%), took place in services other than Infectious Diseases.
      Mean unitary cost per patient per admission, out-patient visits and ER visits
      were similar between groups. Pharmacy costs per year was higher in Spanish
      patients than in immigrants (7351.8 versus 7153.9 euros [year 2005], P=.012).
      There were no differences in the total cost per patient per year between both
      groups. The global distribution of cost was very similar between both groups;
      almost 75% of the total cost was attributed to pharmacy in both groups.
      CONCLUSIONS: There are no significant differences in health resource utilisation
      and associated costs between immigrant and Spanish HIV patients.

PMID- 22377498
TI  - Poultry culling and Campylobacteriosis reduction among humans, the Netherlands.
AB  - In the Netherlands in 2003, an outbreak of avian influenza in poultry resulted in
      extensive culling, especially of layer hens. Concurrently, human
      campylobacteriosis cases decreased, particularly in the culling area. These
      observations raise the hypothesis that Campylobacter spp. dissemination from
      poultry farms or slaughterhouses might contribute to human campylobacteriosis.

PMID- 22377499
TI  - Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in
      patients with Alzheimer's disease.
AB  - BACKGROUND/AIMS: Degeneration of cholinergic neurons in the basal forebrain
      correlates with cognitive decline in patients with Alzheimer's disease (AD).
      Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a
      potential AD therapy due to its regenerative effects on the basal forebrain
      cholinergic neurons in AD animal models. Here we report the results of a first-in
      man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of
      AD patients with the primary objective to explore safety and tolerability.
      METHODS: This was an open-label, 12-month study in 6 AD patients. Patients were
      implanted stereotactically with EC-NGF biodelivery devices targeting the basal
      forebrain. Patients were monitored with respect to safety, tolerability, disease
      progression and implant functionality. RESULTS: All patients were implanted
      successfully with bilateral single or double implants without complications or
      signs of toxicity. No adverse events were related to NGF or the device. All
      patients completed the study, including removal of implants at 12 months.
      Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6
      patients were detected. CONCLUSIONS: This study demonstrates that surgical
      implantation and removal of EC-NGF biodelivery to the basal forebrain in AD
      patients is safe, well tolerated and feasible.

PMID- 22377500
TI  - A program of physical rehabilitation during hemodialysis sessions improves the
      fitness of dialysis patients.
AB  - AIM: The aim of the present study was to evaluate the influence of cycle exercise
      during hemodialysis (HD) on patients' physical proficiency, muscle strength,
      quality of life and selected laboratory parameters. PATIENTS AND METHODS: In a
      group of 29 (15 female, 14 male) HD patients (age 64.2 +/- 13.1 years), 3 months
      of cycle training during dialysis sessions was performed. The following data were
      analyzed: strength of lower extremities (six-minute walk test, isokinetic knee
      extension, flexion peak torque), nutrition parameters (albumin, BMI),
      inflammation intensity (CRP, IL-6), and quality of life (SF-36v2). RESULTS: In
      the six-minute walk test, the increase in walk velocity was 4% (3.56 km/h before
      and 3.73 km/h after cycle training; p < 0.01). At angular velocity (AV) of 60
      degrees /s, extension peak torque in the knee joint rose by 7% and at AV of 300
      degrees /s by 4% (p = 0.04). Flexion peak torque at AV of 180 degrees /s
      increased by 13% (p = 0.0005). The program does not influence nutrition or
      inflammation parameters. No complications directly related to exercise were
      observed. CONCLUSION: Cycle exercise during dialysis is safe even in older HD
      patients with multiple comorbidities. It results in a significant increase in
      general patient walking ability and in a gain in lower extremity muscle strength.

PMID- 22377501
TI  - A case of intra-operative ventricular fibrillation: Electro-cauterization,
      undiagnosed Takotsubo cardiomyopathy or long QT syndrome?
AB  - INTRODUCTION: Cardiac arrest in the perioperative setting is an extremely serious
      event that is estimated to occur between 4.6 and 19.7 per 10,000 anesthetics.(1
      5) While risk factors for cardiac complications can be identified pre-
      operatively, in many cases workup of risk factors are not indicated by standard
      pre-operative testing guidelines. PRESENTATION OF CASE: We present a case of a 47
      year-old female undergoing an elective bilateral mastectomy who suddenly
      converted to ventricular fibrillation. While ventricular fibrillation is not a
      unique finding, our search for its etiology revealed two previously undiagnosed
      cardiac conditions, and possible electro- cautery induced ventricular
      fibrillation. DISCUSSION: In this case study, we discuss the possible etiology of
      ventricular fibrillation in our patient and highlight the importance pre
      operative patient investigation and history provide. CONCLUSION: Searching for
      the potential causes that may have contributed to the cardiac arrest is an
      extremely useful exercise as it allows us to better prepare patients pre
      operatively, improve intra-operative care, and prevent future cardiac events.

PMID- 22377502
TI  - Case report - An acute presentation of lymphangiomatosis.
AB  - INTRODUCTION: Lymphangioma is an uncommon malformation of lymphatic system.
      Multiple colonic lymphangioma named as lymphangiomatosis is considered an
      extremely rare disease. PRESENTATION OF CASE: We report a case of colonic
      lymphangiomatosis presenting as recurrent right iliac fossa pain in a young
      female treated surgically. DISCUSSION: Lymphangiomatosis is a rare but benign
      disease with a variety of presentations. There are few reported cases in the
      literature at present and no guidelines regarding the diagnosis or treatment of
      the same. CONCLUSION: Our case demonstrates an unusual presentation of
      lymphangiomatosis treated surgically. Debate will remain on this rare condition.

PMID- 22377503
TI  - Knowledge, perceptions and attitudes toward complementary and alternative
      therapies among Kuwaiti medical and pharmacy students.
AB  - OBJECTIVE: To determine the knowledge, perceived effectiveness and harmfulness of
      complementary and alternative medicine (CAM) modalities, general attitude and the
      need for education in the use of CAM therapies among medical and pharmacy
      students. METHODS: A descriptive and cross-sectional study was performed using a
      pre-tested questionnaire on a randomly selected sample of 250 students in
      Faculties of Medicine and Pharmacy, Kuwait University. Descriptive and logistic
      regression analyses were used in data analysis. RESULTS: The response rate was
      88.4%. CAM usage was reported by 122 (55.2%) of students, and mostly associated
      with females (OR 4.4, 95% CI 1.7-11.3). Herbal products were the most commonly
      used (83, 37.6%). Knowledge about 11 CAM modalities was generally poor, even
      among the respondents who claimed to know them most. The knowledge about herbal
      products was significantly better among 58 pharmacy students (49.2%) than 32
      medical students (31.4%) (OR 2.0, 95% CI 1.1-3.6). Massage, herbal products and
      prayer/Qur'an reciting were perceived as being the most effective, while
      cauterization as the most harmful. Attitude toward CAM was positive, with 176
      (79.7%) believing that CAM includes ideas and methods from which conventional
      medicine could benefit. Lack of trained professionals and lack of scientific
      evidence were the most perceived barriers for CAM implementation. 198 (89.6%)
      admitted the importance of knowledge about CAM for them as future healthcare
      practitioners. CONCLUSION: The students acknowledged the need to be well educated
      about CAM to better advise their patients in the future.

PMID- 22377504
TI  - Secondary causes of osteoporosis in fracture patients.
AB  - OBJECTIVE: Identification and treatment of osteoporosis in the fragility fracture
      population and interventions to reduce the risk of future fracture are improving
      in orthopaedic practice. This study investigated the prevalence of vitamin D
      insufficiency and deficiency and other secondary causes of low bone density in
      patients who have sustained a fragility fracture and were referred from fracture
      clinic to a metabolic bone disease clinic (MBDC) for further assessment. DESIGN:
      Retrospective chart audit. SETTING: University hospital fracture clinic.
      PATIENTS: Three hundred ninety-nine patients referred from the orthopaedic
      division to the MBDC over a 3-year period. INTERVENTION: A standardized chart
      audit form was developed, and electronic charts were retrospectively audited.
      MAIN OUTCOME MEASUREMENTS: Secondary causes of osteoporosis and routine blood
      test results. RESULTS: Three hundred eight of 399 patients had blood
      investigations completed. A total of 98 patients (32%) had 125 secondary causes
      of osteoporosis other than vitamin D deficiency or insufficiency recorded in
      their electronic chart, including medication use, premature ovarian failure,
      hypogonadism, smoking, excessive alcohol use, renal impairment, gastrointestinal
      conditions, and endocrine conditions. Mean serum vitamin D level was 69.0 nmol/L
      in 83 men and 75.4 nmol/L in 186 women. Serum vitamin D levels were deficient at
      <=25 nmol/L in 7 patients, insufficient at 26-74 nmol/L in 137 patients, and
      sufficient at >=75 nmol/L in 125 patients. Investigation of causes of secondary
      osteoporosis can inform and influence specific treatment regimens. CONCLUSIONS:
      More than one-half of patients sustaining a fragility fracture and referred to
      the MBDC were vitamin D insufficient or deficient, and nearly one-third had a
      secondary cause of osteoporosis other than vitamin D insufficiency/deficiency. A
      standardized list of blood and urine analyses and radiographs has been
      implemented for fragility fracture patients and selected other fracture patients
      who are undergoing investigation for osteoporosis. LEVEL OF EVIDENCE: Prognostic
      Level II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22377505
TI  - Geriatric trauma:  demographics, injuries, and mortality.
AB  - OBJECTIVES: To identify injuries that elderly sustain during high-energy trauma
      and determine which are associated with mortality. DESIGN: Retrospective review
      of prospectively collected database. SETTING: Academic trauma center. PATIENTS:
      Patients selected from database of all trauma admissions from January 2004
      through June 2009. Study population consisted of patients directly admitted from
      scene of injury who sustained high-energy trauma with at least one orthopaedic
      injury and were 65 years or older (n = 597). INTERVENTION: Review of
      demographics, trauma markers, injuries, and disposition statuses. MAIN OUTCOME
      MEASUREMENTS: Statistical analysis using chi test, Student t test, and logistic
      regression analysis. RESULTS: The most common fractures were of the rib, distal
      radius, pelvic ring, facial bones, proximal humerus, clavicle, ankle, and sacrum.
      The injuries associated with the highest mortality rates were fractures of the
      cervical spine with neurological deficit (47%), at the C2 level (44%), and of the
      proximal femur (25%), pelvic ring (25%), clavicle (24%), and distal humerus
      (24%). The fractures significantly associated with mortality were fractures of
      the clavicle (P = 0.001), foot joints (P = 0.001), proximal humerus or shaft and
      head of the humerus (P = 0.002), sacroiliac joint (P = 0.004), and distal ulna (P
      = 0.002). CONCLUSIONS: Elderly patients present with significantly worse
      injuries, remain in the hospital longer, require greater use of resources after
      discharge, and die at 3 times the rate of the younger population. Although the
      high mortality rates associated with cervical spine, hip, and pelvic ring
      fractures were not unexpected, the injuries that were statistically associated
      with mortality were unexpected. Injuries such as clavicle fracture were
      statistically associated with mortality. As our population ages and becomes more
      active, the demographic may gain in clinical importance. LEVEL OF EVIDENCE:
      Prognostic Level II. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 22377506
TI  - A biomechanical comparison of short segment long bone fracture fixation
      techniques:  single large fragment plate versus 2 small fragment plates.
AB  - OBJECTIVES: To determine whether using 2 small fragment plates (3.5 mm screw
      size) side by side is biomechanically superior to the use of 1 large fragment
      plate (4.5 mm screw size), in the fixation of "short segments" in long bone
      fractures. METHODS: Fiber-filled epoxy bone surrogates were plated across 1-cm
      gaps with 3 different constructs. Six surrogates were fixed using 2 side-by-side
      3.5-mm waisted compression plates and six 3.5-mm screws, 6 surrogates were fixed
      using one 4.5-mm waisted compression plate and two 4.5-mm screws, and 6
      surrogates were fixed using one 3.5-mm waisted compression plate and three 3.5-mm
      screws. These constructs then underwent cyclic axial compression in 100-N
      increments until 500 N was reached. Then, they underwent cyclic cantilever
      bending at 2 Hz and at a 23.6 N.m moment until fatigue failure occurred. Also, a
      single load to failure test was performed in cantilever bending to evaluate plate
      strength. RESULTS: The cumulative gap length change after 500 cycles of loading
      up to 500 N was 3.4% +/- 0.4% for the 3.5 mm double plate construct, 9.5% +/-
      1.4% for the 4.5 mm single plate construct, and 14.4% +/- 0.9% for the 3.5 mm
      single plate construct. In cantilever bending, the 3.5 mm double plate construct
      failed after 15,345 +/- 2493 cycles, the 4.5 mm single plate construct failed
      after 2713 +/- 1811 cycles, and the 3.5 mm single plate construct failed in its
      first cycle. In single load to failure testing, the load at offset yield was
      higher in the 3.5 mm double plate construct than the 4.5 mm single plate
      construct. CONCLUSIONS: This study suggests that in situations where anatomy or
      other limitations limit the length of bone segments available for fixation, it
      may be preferable to use 2 small plates with more screws rather than 1 large
      plate with few screws.

PMID- 22377507
TI  - The physiologic and pathologic effects of the reamer irrigator aspirator on fat
      embolism outcome:  an animal study.
AB  - OBJECTIVES: Intramedullary reaming of long bones before nail insertion has been
      known to cause an increase in fat emboli introduction into the bloodstream, which
      is a potentially fatal phenomenon. The goal of this study was to assess whether
      the reamer irrigator aspirator (RIA) reamer can reduce fat embolic load compared
      with the standard AO reamer. METHODS: Fifteen pigs were prepared using an
      intravenous catheter inserted into the marginal ear vein for fluid balance and
      drug administration. One third of the pig's blood volume was withdrawn to
      simulate hemorrhagic shock. Each animal underwent bilateral retrograde femoral
      reaming, cementing, and nailing using either an RIA or AO reamer. Assignment of a
      reamer type to the left or right side was done randomly and allowed for direct
      comparison of matching femur results. Outcome measures were obtained, namely,
      pulmonary arterial pressure, mean arterial pressure, partial pressure of arterial
      oxygen, and cardiac output. Staining techniques were used to ascertain fat emboli
      counts from lung tissue samples. RESULTS: For mean arterial pressure, partial
      pressure of arterial oxygen, and cardiac output after cement injection, the RIA
      reamer group showed statistically higher values than the AO reamer group. In
      corollary, the RIA showed statistically lower pulmonary arterial pressure levels.
      No differences were noted at baseline, during hypovolemia, and post
      resuscitation. With the Student t test, no statistical differences were found
      between reamers regarding fat emboli counts for both staining methods. With the
      Mann-Whitney test, the RIA reamer showed statistically fewer emboli (7.0 versus
      74.5) (P = 0.02, Z = 2.33) using Oil Red "O" staining. CONCLUSIONS: The RIA
      reamer demonstrated superior results with respect to physiologic measures and fat
      emboli counts and may provide optimal results compared with the AO reamer.

PMID- 22377508
TI  - The biomechanical effect of prosthetic design on radiocapitellar stability in a
      terrible triad model.
AB  - OBJECTIVES: The integrity of elbow soft tissues affects radiocapitellar joint
      stability in the presence of bipolar radial head (RH) prostheses. This study
      examined the effect on radiocapitellar stability of monopolar designs versus
      bipolar RH prostheses in an elbow model with a surgically controlled terrible
      triad injury. METHODS: In each of 8 fresh-frozen elbow specimens (4 male and 4
      female), a terrible triad fracture dislocation was created through soft tissue
      releases, coronoid fracture, and RH resection. Radiocapitellar stability was
      recorded under the following 3 sets of conditions: (1) surgical control (native
      RH), (2) RH replacement (circular monopolar or bipolar), (3) replacement with
      alternate circular RH not used in condition 2, and (4) replacement with the
      anatomic RH. RESULTS: The type of RH used significantly impacted the mean peak
      force required to resist posterior subluxation (p = 0.0001). The mean peak
      subluxation force of the bipolar prosthesis (1 +/- 1 N) was significantly less
      than both the anatomic (16 +/- 1 N) and nonanatomic circular (12 +/- 1 N)
      implants (p = 0.0002). The peak subluxation force of the native RH (18 +/- 2 N)
      was not different than the anatomic implant (p = 0.09) but was greater than the
      nonanatomic circular design (p = 0.0006). CONCLUSIONS: Monopolar RHs confer
      greater radiocapitellar stability than bipolar implants in the setting of
      terrible triad injuries. Of the 2 monopolar designs tested, the anatomic design
      provided more stability than the non-anatomic RH prosthesis.

PMID- 22377509
TI  - Intramedullary skeletal kinetic distractor in the treatment of leg length
      discrepancy--a review of 16 cases and analysis of complications.
AB  - OBJECTIVE: The intramedullary skeletal kinetic distractor (ISKD; Orthofix) is a
      relatively new device available for limb lengthening. This fully implantable
      mechanical nail promises reduced morbidity over traditional methods where
      external fixation is used. We report on our experience using this device in
      treating 16 patients with leg length discrepancy. DESIGN: Retrospective review of
      16 consecutive patients treated with ISKD. SETTING: Tertiary trauma hospital.
      PATIENTS: Thirteen males and 3 females were treated with the ISKD between 2004
      and 2009. There were 11 femora and 5 tibiae. The indication for lengthening was
      posttraumatic shortening in 15 patients and congenital hypoplasia in the
      remaining patient. OUTCOME MEASURES: Limb length gained, rate of lengthening,
      time to consolidation, complications, and factors that may be associated with
      complications. RESULTS: All patients in the series successfully completed
      treatment and reached the desired limb length with radiographic evidence of
      consolidation. The average leg length increase was 35 mm (21-75 mm). No
      infection, malunion, or joint contracture was observed. A length of less than 100
      mm of the thick portion of the nail in the distal fragment is associated with the
      likelihood of a "runaway nail" (distraction index > 1.5 mm/d). Six patients had
      poor regenerate requiring bone grafting. Likelihood of poor regenerate was
      associated with number of previous operations on the lengthened bone. Three
      patients had nails that were difficult to distract and required closed
      manipulation under anesthesia. CONCLUSIONS: The ISKD is an effective method for
      correcting leg length discrepancies. Complications are frequent but are
      manageable with standard techniques. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22377510
TI  - Regional anesthesia improves outcome after distal radius fracture fixation over
      general anesthesia.
AB  - OBJECTIVE: To compare the efficacy of anesthetic type on clinical outcomes after
      operative treatment of distal radius fractures. DESIGN: Retrospective review of
      prospectively collected data. SETTING: Academic medical center. PATIENTS: One
      hundred eighty-seven patients with a distal radius fracture (OTA type 23) were
      identified within a registry of 600 patients. INTERVENTION: Patients with
      operative distal radius fractures underwent open reduction and internal fixation
      with a volarly applied plate and screws under regional or general anesthesia.
      MAIN OUTCOME MEASUREMENTS: Clinical, radiographic, and patient-based functional
      outcomes were recorded at routine postoperative intervals. Complications were
      recorded. RESULTS: One hundred eighty-seven patients met inclusion criteria and
      had a minimum of 1-year follow-up. There were no differences between the groups
      with regard to patient demographics or fracture types treated. At both 3 and 6
      months post surgery, pain was diminished among those patients who received a
      regional block. Wrist and finger range of motion for patients who received
      regional versus general anesthesia was improved at all follow-up points. Patients
      who received regional anesthesia also had higher functional scores as measured by
      the Disabilities of the Arm, Shoulder and Hand at 3 months (P = 0.04) and 6
      months (P = 0.02). CONCLUSION: Patients who are candidates should be offered
      regional anesthesia when undergoing repair of a displaced distal radius fracture.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 22377511
TI  - Neural correlates of depressive realism--an fMRI study on causal attribution in
      depression.
AB  - BACKGROUND: Biased causal attribution is a critical factor in the cognitive model
      of depression. Whereas depressed patients interpret events negatively, healthy
      people show a self-serving bias (internal attribution of positive events and
      external attribution of negative events). METHODS: Using fMRI, depressed patients
      (n=15) and healthy controls (n=15) were confronted with positive and negative
      social events and made causal attributions (internal vs. external). Functional
      data were analyzed using a mixed effects model. RESULTS: Behaviourally, controls
      showed a self-serving bias, whereas patients demonstrated a balanced
      attributional pattern. Analysis of functional data revealed a significant group
      difference in a fronto-temporal network. Higher activation of this network was
      associated with non self-serving attributions in controls but self-serving
      attributions in patients. Applying a psycho-physiological interaction analysis,
      we observed reduced coupling between a dorsomedial PFC seed region and limbic
      areas during self-serving attributions in patients compared to controls.
      LIMITATIONS: Results of the PPI analysis are preliminary given the liberal
      statistical threshold. CONCLUSIONS: The association of the behaviourally less
      frequent attributional pattern with activation in a fronto-temporal network
      suggests that non self-serving responses may produce a self-related response
      conflict in controls, while self-serving responses produce this conflict in
      patients. Moreover, attribution-modulated coupling between the dorsomedial PFC
      and limbic regions was weaker in patients than controls. This preliminary finding
      suggests that depression may be associated with disturbances in fronto-limbic
      coupling during attributional decisions. Our results implicate that treatment of
      major depression may benefit from approaches that facilitate reinterpretation of
      emotional events in a more positive, more self-serving way.

PMID- 22377512
TI  - A randomized, placebo- and active-controlled study of paliperidone extended
      release as maintenance treatment in patients with bipolar I disorder after an
      acute manic or mixed episode.
AB  - BACKGROUND: Paliperidone ER monotherapy was efficacious in treating acute mania
      in two 3-week studies in patients with bipolar I disorder. We assessed its
      efficacy in a study investigating maintenance treatment of clinically stable
      patients with this disorder. METHODS: Patients (n=766), aged 18 to 65 years
      inclusive, with current manic or mixed episodes were initially randomized (4:1)
      to flexibly-dosed paliperidone ER (3-12 mg/day) or olanzapine (5-20 mg/day; 3
      week acute treatment phase); responders continued the same treatment (12-week
      continuation phase). Patients on paliperidone ER who achieved remission during
      this phase were randomized (1:1) to fixed-dose paliperidone ER (n=152) or placebo
      (n=148); those on olanzapine continued to receive that at fixed dose (n=83)
      (maintenance phase). RESULTS: Median time to recurrence of any mood symptoms
      (primary endpoint) was: 558 days (paliperidone ER), 283 days (placebo) and not
      observed with olanzapine (<50% of patients experienced recurrence). Time to
      recurrence of any mood symptoms was significantly longer with paliperidone ER
      than placebo (p=0.017; based on weighted Z-test at 0.0198 significance level;
      hazard ratio [placebo: paliperidone ER; unweighted 95% confidence interval]: 1.43
      [1.03; 1.98]); the difference was significant for preventing recurrence of manic,
      but not depressive, symptoms. Treatment-emergent adverse events (maintenance
      phase) occurred more often in olanzapine group (64%) than placebo (59%) or
      paliperidone ER groups (55%). LIMITATIONS: Responder-enriched design prevents
      extrapolation of data to patients not previously stabilized on paliperidone ER.
      CONCLUSIONS: Paliperidone ER significantly delayed the time to recurrence of any
      mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety
      concerns emerged.

PMID- 22377513
TI  - Acculturation and post-disaster mental health problems among affected and non
      affected immigrants: a comparative study.
AB  - BACKGROUND: It is unknown to what extent acculturation among disaster-affected
      immigrants is associated with mental health problems (MHP) compared to non
      affected immigrants. METHODS: We examined the associations between acculturation
      and post-disaster MHP among affected and non-affected immigrants in The
      Netherlands. RESULTS: Among the affected group, keeping norms and values of
      original culture and limited skills to cope with the demands of the new society
      were independently associated with PTSD-symptomatology, anxiety, depression,
      hostility, and somatic problems at 18 months post-event. In the non-affected
      comparison group no associations were found. Interestingly, levels of
      acculturation did not differ between both groups, in contrast to MHP.
      LIMITATIONS: The acculturation levels could be influenced by the experience of a
      disaster. However, levels did not differ statistically between the study groups.
      Furthermore, the groups were reasonably small and the response rates were,
      although not uncommon in health studies among immigrants, relatively low.
      CONCLUSIONS: The findings of this unique study clearly suggest that post-disaster
      mental health policies should target low levels of skills to survive in the new
      society. Furthermore, the acculturation domain of keeping traditional norms and
      values can be contrary to the Dutch care after a disaster where self-efficacy and
      individualistic, cognitive functioning are the central goals. Further research is
      warranted to explore and examine post-event interventions aimed at increasing the
      levels of acculturation that may facilitate recovery.

PMID- 22377514
TI  - The SAR development of dihydroimidazoisoquinoline derivatives as
      phosphodiesterase 10A inhibitors for the treatment of schizophrenia.
AB  - The identification of potent and orally active dihydroimidazoisoquinolines as PDE
      10A inhibitors is reported. The SAR development led to the discovery of compound
      35 as a potent, selective, and orally active PDE10A inhibitor. Compound 35
      inhibited MK-801-induced hyperactivity at 3mg/kg and displayed a 10-fold
      separation between the minimal effective doses for inhibition of MK-801-induced
      hyperactivity and hypolocomotion in rats.

PMID- 22377515
TI  - Verrulactones A and B, new inhibitors of Staphylococcus aureus enoyl-ACP
      reductase produced by Penicillium verruculosum F375.
AB  - New dimeric compounds of alternariol class, verrulactones A and B, were isolated
      from a culture broth of the fungal strain Penicillium verruculosum F375 and their
      structure were established by various spectral analysis. Verrulactones A and B
      strongly inhibited Staphylococcus aureus enoyl-ACP reductase with IC(50) of 0.92
      and 1.41 MUM, respectively, and also showed antibacterial activity against S.
      aureus and MRSA with MICs of 8 and 16 MUg/mL, respectively.

PMID- 22377516
TI  - Synthesis and biological properties of chemically modified siRNAs bearing 1-deoxy
      D-ribofuranose in their 3'-overhang region.
AB  - To elucidate the role of the sugar moiety in the two natural nucleotides of the
      3'-overhang region of small interfering RNA (siRNA), we synthesized siRNAs that
      incorporated two abasic nucleosides, 1-deoxy-D-ribofuranose (R(H)). We improved
      the method for preparing an O-protected abasic nucleoside, 1-deoxy-2,3,5-tri-O
      benzoyl-beta-D-ribofuranose, via the reductive cleavage of the anomeric position
      of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose. To incorporate R(H) into
      oligonucleotides by the standard phosphoramidite solid phase method, R(H) was
      converted into its phosphoramidite derivative and the solid support linked to a
      controlled pore glass resin. Chemically modified RNAs possessing R(H) at the 3'
      overhang region were easily prepared in good yields. siRNAs containing R(H)
      showed moderate nuclease-resistance and a desirable knockdown effect.

PMID- 22377517
TI  - Design of oxobenzimidazoles and oxindoles as novel androgen receptor antagonists.
AB  - Oxobenzimidazoles (e.g., 1), a novel series of androgen receptor (AR)
      antagonists, were discovered through de novo design guided by structure-based
      drug design. The compounds in this series were reasonably permeable and
      metabolically stable, but suffered from poor solubility. The incorporation of
      three dimensional structural features led to improved solubility. In addition,
      the observation of a 'flipped' binding mode of an oxobenzimidazole analog in an
      AR ligand binding domain (LBD) model, led to the design and discovery of the
      novel oxindole series (e.g., 2) that is a potent full antagonist of AR.

PMID- 22377518
TI  - Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as
      trypanosomal PDE inhibitors. Part 2. Tadalafil analogs.
AB  - In this Letter we describe our ongoing target repurposing efforts focused on
      discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1.
      This enzyme has been implicated in virulence of Trypanosoma brucei, the causative
      agent of human African trypanosomiasis (HAT). We outline the synthesis and
      biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently
      utilized for treatment of erectile dysfunction, and report that these analogs are
      weak inhibitors of TbrPDEB1.

PMID- 22377519
TI  - An example of designed multiple ligands spanning protein classes: dual MCH-1R
      antagonists/DPPIV inhibitors.
AB  - A ligand-based approach to identify potential starting points for a dual MCH-1R
      antagonist/DPPIV inhibitor medicinal chemistry program was undertaken. Potential
      ligand pairs were identified by analysis of MCH-1R and DPPIV in vitro data. A
      highly targeted synthetic effort lead to the discovery of pyridone 11, a dual MCH
      1R antagonist/DPPIV inhibitor with selectivity over DPP8 and DPP9.

PMID- 22377520
TI  - MRI/SPECT-based diagnosis and CT-guided high-intensity focused-ultrasound
      treatment system in MPTP mouse model of Parkinson's disease.
AB  - Single-photon emission computed tomography (SPECT) of dopamine transporters with
      (99m)Tc-TRODAT-1 has recently been proposed to offer valuable information for the
      diagnosis of Parkinson's disease (PD). Furthermore, High-intensity focused
      ultrasound (HIFU) is a newly developed technique in which the energy of
      ultrasound wave is directed to a focused spot for the purpose treatment of PD.
      This study presents a diagnosis and image-guided system using HIFU to treat the
      mouse with PD under a designed stereotactic frame. The system comprises two key
      components: an automatic atlas-based SPECT/MRI image registration module for
      diagnosis and a stereotactic CT-guided module for HIFU treatment. The SPECT/MR
      image registration here is important in the non-invasive examination of the
      dopamine concentration in vivo. From the experimental results, the image
      registration module proves to have comparable performance to that derived from
      manual drawing by experts. In addition, the stereotactic CT-guided module
      achieved a positioning accuracy to within 2mm on the average, which is acceptable
      for the purpose of HIFU treatment.

PMID- 22377522
TI  - Prevalence of wheat allergy  in Japanese adults.
AB  - BACKGROUND: Wheat is one of the most common causes of food allergies. The exact
      prevalence of wheat allergy has not been well delineated in Japanese adults.
      METHODS: We enrolled 935 adults in a cohort study established by Shimane
      University in order to examine the determinants of lifestyle-related diseases. A
      screening was conducted by a questionnaire-based examination and a detection of
      serum omega-5 gliadin-specific IgE. Subjects who tested positive in the
      questionnaire-based examination and/or the serum omega-5 gliadin-specific IgE
      test were further examined by detailed interviews and skin prick tests. RESULTS:
      A total of 22 subjects were picked up by the screening process, and 17 of these
      were further examined by secondary testing. Only two subjects were conclusively
      identified as having wheat allergy. CONCLUSIONS: The prevalence of wheat allergy
      in Japanese adults was found to be 0.21% by using a combination of questionnaire
      based examination, skin prick test and serum omega-5 gliadin-specific IgE test.

PMID- 22377523
TI  - Prophylactic probiotics reduce cow's milk protein intolerance in neonates after
      small intestine surgery and antibiotic treatment presenting symptoms that mimics
      postoperative infection.
AB  - BACKGROUND: To examine occurrence of cow's milk protein intolerance (CMPI) in
      newborns that underwent small intestine surgery and the clinical profiles of
      those newborns with postoperative CMPI, and to evaluate the preventive effects of
      probiotics on CMPI. METHODS: We retrospectively reviewed from 2000 to 2009, a
      total of 30 newborns required surgery on their small intestines. All of these
      patients had received antibiotics to prevent postoperative infection. Since 2005
      we adopted a protocol of targeted probiotic therapy prophylaxis. RESULTS:
      Eighteen patients received probiotic therapy, while twelve did not. One infant
      among those eighteen patients and eight patients among those twelve developed
      CMPI, a significantly lower rate for the group with probiotic therapy than that
      without it (p < 0.001). Patients with positive cultures for gram positive and
      gram negative organisms increased in number before and after surgery but then
      decreased after probiotics treatment. Poor weight gain, gastrointestinal
      symptoms, and rise in C reactive protein (CRP) levels were observed in all of
      those nine CMPI patients. Specific IgE antibodies were elevated in four of the
      nine subjects, and total IgE levels were elevated in seven of them. All CMPI
      patients had increased level of CRP without proven infections. CONCLUSIONS: CMPI
      was induced in newborns after surgery on their small intestines and antibiotics
      treatment with presentation of symptoms that mimic postoperative infection.
      Development of CMPI in this population possibly involves disruption of intestinal
      flora. Administration of probiotics can reduce the incidence of CMPI after small
      intestine surgery. The elevated CRP level may be useful in the diagnosis of CMPI.

PMID- 22377524
TI  - Cytokine profiles in Japanese patients with chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is classified in CRS without nasal polyp
      (CRSsNP) and CRS with nasal polyp (CRSwNP) in western countries, whereas this
      classification was not common so far in Japan. Studying inflammatory mediators in
      clearly defined disease subgroups may lead to a better differentiation of chronic
      sinus diseases. METHODS: Homogenates of sinonasal mucosal tissue from 14
      controls, 9 CRSsNP patients, and 19 CRSwNP patients were assayed for transforming
      growth factor (TGF)-beta, interleukin (IL)-5, immunoglobulin E (IgE),
      Staphylococcus enterotoxin (SAE)-IgE, eosinophil-catioic protein (ECP),
      myeloperoxidase (MPO), IL-1beta, IL-6, and IL-8 by enzyme-linked immunosorbent
      assay or UNICAP system. RESULTS: CRSwNP had significantly higher levels of IL-5,
      IgE, SAE-IgE, and ECP compared with CRSsNP and controls. CRSsNP was characterized
      by high levels of TGF-beta, while CRSwNP showed a Th2 polarization and lower
      levels of TGF-beta. Especially, in CRSwNP samples, 68.4% were eosinophilic
      (ECP/MPO ratio >1), and 52.6% were SAE-IgE positive. On the other hand, in 9
      CRSsNP patients, eosinophilic or SAE-IgE positive sample was only one sample
      respectively. Additionally, 31.6% of CRSwNP were asthmatic patients, while none
      of CRSsNP patient was suffering from bronchial asthma. CONCLUSIONS: This study is
      thought to be the first one that showed the cytokine profiles in Japanese
      CRSs/wNP similar to those of European CRS. Based on mediator profiles, we suggest
      that CRSsNP and CRSwNP are distinct disease entities within the group of chronic
      sinus diseases.

PMID- 22377525
TI  - Cough triggers and their  pathophysiology in patients with prolonged or chronic
      cough.
AB  - BACKGROUND: The character or timing of chronic cough is considered to be
      unpredictable for diagnosing its cause. However, the associations of cough
      triggers with cough pathophysiology remains unknown. METHODS: We developed a
      closed questionnaire listing 18 triggers that were reported by >=1% of 213
      patients in a retrospective survey. Using this questionnaire, patients with cough
      predominant or cough-variant asthma (n = 140) and those with non-asthmatic cough
      (54) were asked whether their cough was induced by the listed triggers.
      Associations of triggers with causes of cough, airway sensitivity to inhaled
      methacholine, exhaled nitric oxide (NO) levels, number of sensitizing allergens,
      and scores from gastroesophageal reflux (GER) questionnaires were examined.
      Factor analysis was used to categorize variables, including the 12 most common
      cough triggers, diagnosis of asthmatic cough, airway sensitivity, and exhaled NO
      levels. RESULTS: "Cold air" and "fatigue/stress" induced cough more often in
      asthmatic coughers than in non-asthmatic coughers. "Spices" and "meals" induced
      cough more frequently in GER-coughers (n = 19). Patients who marked "cold air" as
      the trigger were more sensitive to inhaled methacholine and showed higher exhaled
      NO levels than those who did not mark this trigger. The "post-nasal drip" trigger
      was associated with elevated exhaled NO levels, and this association was mainly
      exhibited by patients with cough-predominant asthma. The triggers "pollen" and
      "mold smell" were associated with a number of sensitizing allergens. The number
      of triggers was weakly associated with GER scores. By factor analysis, "cold
      air," "fatigue/stress," asthmatic cough, airway hypersensitivity, and elevated NO
      levels were categorized into the same factor. CONCLUSIONS: Several cough triggers
      may reflect the pathophysiology of prolonged or chronic cough.

PMID- 22377526
TI  - Niflumic acid inhibits goblet cell degranulation in a guinea pig asthma model.
AB  - BACKGROUND: Human Ca(2+)-activated Cl ion channel 1 (hCLCA1) is expressed in
      goblet cell hyperplasia in the airway of asthmatics, and murine CLCA3 is
      associated with antigen-sensitized and IL-13-induced goblet cell metaplasia in
      mice. However, the role of CLCA in goblet cell degranulation is not fully
      investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits
      goblet cell metaplasia, but the effect of NFA on goblet cell degranulation has
      not been determined in an asthma model. METHODS: Guinea pigs were sensitized with
      ovalbumin (OA) twice and then challenged with saline, OA, histamine, and one of
      the Ca(2+)-dependent secretagogues, UTP. The PAS/AB-stained mucus area in the
      tracheal epithelium was measured with a computer image analysis system, and the
      morphology of mucus granules was examined by transmission electron microscopy. In
      the in vitro experiment, goblet cells cultured with IL-13 at the air-liquid
      interface were stimulated with UTP in the presence or absence of NFA, and the
      MUC5AC level in cell lysates was measured by ELISA. RESULTS: The mucus areas were
      smaller in the OA-, histamine-, and UTP-challenged animals than in the saline
      challenged animals. NFA inhibited the decrease in mucus area and morphological
      changes in mucus granules. UTP caused swelling and exocytosis of mucus granules
      and MUC5AC secretion by cultured goblet cells, and NFA inhibited these changes.
      CONCLUSIONS: NFA inhibited the secretory response of mucus granules in an asthma
      model, suggesting that CLCA may be associated with goblet cell degranulation and
      that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma.

PMID- 22377527
TI  - The definitive diagnostic process and successful treatment for ABPM caused by
      Schizophyllum commune: a report of two cases.
AB  - BACKGROUND: Although mucoid impaction of the bronchi (MIB) is a well-known
      manifestation in allergic bronchopulmonary mycosis (ABPM), when unknown samples
      or plural eumycetes are cultured from bronchial materials, several problems are
      encountered which can affect the definitive diagnostic process or successful
      treatment. CASE SUMMARY: The definitive diagnostic process of two patients [a 58
      (Case 1) and a 70-(Case 2) year-old female] with MIB was: 1) to identify the
      existence of any allergic respiratory disorder, 2) to detect the fungi obtained
      from bronchial materials, with use of the 28S rDNA sequencing and analysis, 3) to
      investigate whether the detected fungus was a probable etiologic antigen, and 4)
      to make the final diagnosis based on the results of the inhalation examinations
      using the antigenic solution of the fungi. As a treatment strategy, bronchial
      toilet and low dose itraconazole therapy were planned according to the clinical
      manifestations of each patient. DISCUSSION: The two patients with MIB were
      successfully diagnosed as ABPM caused by Schizophyllum commune (Sc-ABPM)
      accompanied with hyperattenuating mucoid impaction. The reliability of some
      allergological makers as a substitution for the bronchoprovocation test should be
      clarified in near future. Clinical manifestations demonstrated in our cases
      suggested that the allergic reaction such as eosinophilic bronchoalveolitis
      spreading around the mucus plug was a primary lesion underlying the Sc-ABPM. The
      success of the treatment for Sc-ABPM will be achieved by the strategy targeting
      to fundamental condition and by the control of the disease recurrence by means of
      effective environmental management.

PMID- 22377528
TI  - Fetuin-A is inversely associated with coronary artery calcification in community
      living persons: the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Fetuin-A is a hepatic secretory protein that inhibits arterial
      calcification in vitro. The association of fetuin-A with coronary arterial
      calcification (CAC) in the general population is uncertain. METHODS: Among 2457
      community-living individuals without cardiovascular disease (CVD), we measured
      serum fetuin-A concentrations by ELISA and evaluated the cross-sectional
      association of fetuin-A with CAC prevalence (any vs none) and severity; on follow
      up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC
      incidence and progression. RESULTS: The mean age was 62 (SD 10) years, and the
      mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals
      (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline,
      there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence.
      In models adjusted for demographics, traditional cardiovascular disease (CVD)
      risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%
      13%; P = 0.04) greater CAC prevalence compared with quartiles 2-4. Similar
      associations were observed with CAC severity at baseline, but the association was
      more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI
      3%-21%; P = 0.01) greater CAC severity in adjusted models. There was no
      significant association of fetuin-A with CAC incidence or progression.
      CONCLUSIONS: Fetuin-A is inversely associated with CAC severity among community
      living individuals without CVD. Whether fetuin-A concentrations are associated
      with incident CVD event in the general population requires future study.

PMID- 22377529
TI  - Measurement of late-night salivary cortisol and cortisone by LC-MS/MS to assess
      preanalytical sample contamination with topical hydrocortisone.

PMID- 22377530
TI  - Establishing pediatric reference intervals: a challenging task.

PMID- 22377531
TI  - Sidedness of interfacial arginine residues and anti-atherogenicity of
      apolipoprotein A-I mimetic peptides.
AB  - To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I
      mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011.
      Sequence conservation of apolipoprotein A-I affords novel insights into HDL
      structure-function. J. Lipid Res. 52: 435-450.), may be important for biological
      activity, we compared properties of 4F and analogs, [K4,15>R]4F and [K9,13>R]4F,
      with Lys>Arg substitutions on the right and left side, respectively, of the 4F
      amphipathic helix. Intraperitoneal administration of these peptides into female
      apoE null mice (n = 13 in each group) reduced en face lesions significantly
      compared with controls; 4F and [K4,15>R]4F were equally effective whereas
      [K9,13>R]4F was less effective. Turnover experiments indicated that [K4,15>R]4F
      reached the highest, whereas [K9,13>R]4F had the lowest, plasma peak levels with
      a similar half life as the [K4,15>R]4F analog. The half life of 4F was two times
      longer than the other two peptides. The order in their abilities to associate
      with HDL in human plasma, generation of apoA-I particles with pre-beta mobility
      from isolated HDL, lipid associating ability, and sensitivity of lipid complexes
      to trypsin digestion was: 4F>[K4,15,>R]4F>[K9,13>R]4F. These studies support our
      hypothesis that the sidedness of interfacial Arg residues in the polar face of
      apoA-I mimetics results in differential biological properties.

PMID- 22377532
TI  - Cell density-dependent reduction of dihydroceramide desaturase activity in
      neuroblastoma cells.
AB  - We applied a metabolic approach to investigate the role of sphingolipids in cell
      density-induced growth arrest in neuroblastoma cells. Our data revealed that
      sphingolipid metabolism in neuroblastoma cells significantly differs depending on
      the cells' population context. At high cell density, cells exhibited G0/G1 cell
      cycle arrest and reduced ceramide, monohexosylceramide, and sphingomyelin,
      whereas dihydroceramide was significantly increased. In addition, our metabolic
      labeling experiments showed that neuroblastoma cells at high cell density
      preferentially synthesized very long chain (VLC) sphingolipids and dramatically
      decreased synthesis of sphingosine-1-phosphate (S1P). Moreover, densely populated
      neuroblastoma cells showed increased message levels of both anabolic and
      catabolic enzymes of the sphingolipid pathway. Notably, our metabolic-labeling
      experiments indicated reduced dihydroceramide desaturase activity at confluence,
      which was confirmed by direct measurement of dihydroceramide desaturase activity
      in situ and in vitro. Importantly, we could reduce dihydroceramide desaturase
      activity in low-density cells by applying conditional media from high-density
      cells, as well as by adding reducing agents, such as DTT and L-cysteine to the
      media. In conclusion, our data suggest a role of the sphingolipid pathway,
      dihydroceramides desaturase in particular, in confluence-induced growth arrest in
      neuroblastoma cells.

PMID- 22377533
TI  - Cholesterol level influences opioid signaling in cell models and analgesia in
      mice and humans.
AB  - Cholesterol regulates the signaling of u-opioid receptor in cell models, but it
      has not been demonstrated in mice or humans. Whether cholesterol regulates the
      signaling by mechanisms other than supporting the entirety of lipid raft
      microdomains is still unknown. By modulating cholesterol-enriched lipid raft
      microdomains and/or total cellular cholesterol contents in human embryonic kidney
      cells stably expressing u-opioid receptor, we concluded that cholesterol
      stabilized opioid signaling both by supporting the lipid raft's entirety and by
      facilitating G protein coupling. Similar phenomena were observed in the primary
      rat hippocampal neurons. In addition, reducing the brain cholesterol level with
      simvastatin impaired the analgesic effect of opioids in mice, whereas the opioid
      analgesic effect was enhanced in mice fed a high-cholesterol diet. Furthermore,
      when the records of patients were analyzed, an inverse correlation between
      cholesterol levels and fentanyl doses used for anesthesia was identified, which
      suggested the mechanisms above could also be applicable to humans. Our results
      identified the interaction between opioids and cholesterol, which should be
      considered in clinics as a probable route for drug-drug interaction. Our studies
      also suggested that a low cholesterol level could lead to clinical issues, such
      as the observed impairment in opioid functions.

PMID- 22377534
TI  - Large pelvic masses of obscure origin: urologist's perspective.
AB  - BACKGROUND: Large pelvic masses pose unique diagnostic and therapeutic challenges
      due to varied aetiology, paucity of characteristic imaging features, lack of
      therapeutic algorithms and surgical difficulties in resection inside the narrow
      confines of the pelvis with close proximity of vital structures. METHODS: Records
      of 22 patients with large pelvic masses in the last six years were analysed.
      Their demographic and clinical features were noted, along with imaging features,
      preoperative biopsy, surgical procedure, intraoperative difficulties,
      complications, adjuvant therapy and outcome. RESULTS: There were 14 men and 8
      women with a median age of 45 years. Presenting symptoms were abdominal mass,
      pain, lower urinary tract symptoms, urinary retention and constipation. Imaging
      was mostly unable to determine the organ of origin of the tumour. Histopathology
      revealed pelvic fibromatosis (2), chondrosarcoma (1), liposarcoma (1),
      haemangioendothelioma (1), lymphangioma (2), fibroleiomyoma (1), leiomyosarcoma
      (3), schwannoma (4), malignant nerve sheath tumour (1), rectal gastrointestinal
      stromal tumour (1), retrovesical hydatid cysts (3), sacral chordoma (1) and
      Ewing's sarcoma (1). In 5 patients complete excision was not possible because of
      extension into vital structures. Fifteen patients were alive at 1-5 years of
      follow-up. CONCLUSIONS: Urologists, being the 'gatekeepers of the pelvis', are
      usually involved in the management of large pelvic masses. Good outcome can be
      achieved with careful surgical planning.

PMID- 22377536
TI  - [Minimally invasive treatment of chronic subdural haematoma in adults: results in
      116 patients].

PMID- 22377537
TI  - Characterization of madurastatin C1, a novel siderophore from Actinomadura sp.

PMID- 22377538
TI  - Structure-based design and screening of inhibitors for an essential bacterial
      GTPase, Der.
AB  - Der is an essential and widely conserved GTPase that assists assembly of a large
      ribosomal subunit in bacteria. Der associates specifically with the 50S subunit
      in a GTP-dependent manner and the cells depleted of Der accumulate the
      structurally unstable 50S subunit, which dissociates into an aberrant subunit at
      a lower Mg(2+) concentration. As Der is an essential and ubiquitous protein in
      bacteria, it may prove to be an ideal cellular target against which new
      antibiotics can be developed. In the present study, we describe our attempts to
      identify novel antibiotics specifically targeting Der GTPase. We performed the
      structure-based design of Der inhibitors using the X-ray crystal structure of
      Thermotoga maritima Der (TmDer). Virtual screening of commercially available
      chemical library retrieved 257 small molecules that potentially inhibit Der
      GTPase activity. These 257 chemicals were tested for their in vitro effects on
      TmDer GTPase and in vivo antibacterial activities. We identified three
      structurally diverse compounds, SBI-34462, -34566 and -34612, that are both
      biologically active against bacterial cells and putative enzymatic inhibitors of
      Der GTPase homologs. We also presented the possible interactions of each compound
      with the Der GTP-binding site to understand the mechanism of inhibition.
      Therefore, our lead compounds inhibiting Der GTPase provide scaffolds for the
      development of novel antibiotics against antibiotic-resistant pathogenic
      bacteria.

PMID- 22377539
TI  - Mass spectral measurements of the apoHDL in horse (Equus caballus) cerebrospinal
      fluid.
AB  - As a continuation of our proteogenomic studies of equine apolipoproteins, we have
      obtained molecular masses for several of the apolipoproteins associated with the
      HDL in horse cerebrospinal fluid (CSF). Using electrospray-ionization mass
      spectrometry (ESI-MS), we report on values for apolipoproteins, A-I and A-II, as
      well as acylated apoA-I. In comparison with our previously published data on
      equine plasma apolipoproteins, there appears to be a higher percentage of
      acylated apoA-I in the CSF than in plasma. As was the case in plasma, apoA-II
      circulates as a homodimer. These studies also revealed a protein with a mass of
      34,468Da that we are speculating is the value for horse apoE.

PMID- 22377540
TI  - Oxytocin, but not vasopressin, increases both parochial and universal altruism.
AB  - In today's increasingly interconnected world, deciding with whom and at what
      level to cooperate becomes a matter of increasing importance as societies become
      more globalized and large-scale cooperation becomes a viable means of addressing
      global issues. This tension can play out via competition between local (e.g.
      within a group) and global (e.g., between groups) interests. Despite research
      highlighting factors influencing cooperation in such multi-layered situations,
      their biological basis is not well understood. In a double-blind placebo
      controlled study, we investigated the influence of intranasally administered
      oxytocin and arginine vasopressin on cooperative behavior at local and global
      levels. We find that oxytocin causes an increase in both the willingness to
      cooperate and the expectation that others will cooperate at both levels. In
      contrast, participants receiving vasopressin did not differ from those receiving
      placebo in their cooperative behavior. Our results highlight the selective role
      of oxytocin in intergroup cooperative behavior.

PMID- 22377542
TI  - System-based strategies.

PMID- 22377543
TI  - The importance of detecting anxiety in primary care.

PMID- 22377541
TI  - Social stress interacts with diet history to promote emotional feeding in
      females.
AB  - Stress-induced eating disorders cause significant health problems and are often
      co-morbid with mood disorders. Emotional feeding, particularly in women, may be
      important for the development of obesity and failed attempts to lose weight.
      However, prospective studies assessing the effect of chronic psychosocial stress
      on appetite in different dietary environments in females are lacking. The present
      study tested the hypothesis that chronic psychosocial stress would increase
      consumption of high caloric diet and this emotional feeding would persist even
      when a healthier diet was available. Socially housed female rhesus monkeys were
      studied to address whether subordination increases caloric intake when a high fat
      and sugar diet (HFSD) was available concurrently with a low fat, high fiber diet
      (LCD). Cortisol responsivity and food intake were quantified during this choice
      phase and when only the LCD was available. The order of diet condition was
      counterbalanced to assess whether a history of HFSD would affect appetite. All
      females preferred the HFSD but subordinates consumed significantly more calories
      during the choice phase. The increased calorie intake was maintained in
      subordinate monkeys even after withdrawal of the HFSD. Subordinate females
      demonstrated reduced glucocorticoid negative feedback, with post dexamethasone
      serum cortisol levels significantly predicting intake of the HFSD but not the LCD
      during the choice condition. The cortisol response to an acute stressor
      significantly predicted subsequent intake of a HFSD in all females. Continual
      exposure to the psychosocial stress of subordination in female monkeys results in
      excess caloric intake of foods that mimic a western dietary environment. In
      addition, this social stressor interacts with a history of HFSD intake to promote
      increased feeding even in a healthy dietary environment.

PMID- 22377544
TI  - Validation of the GAD-7 (Malay version) among women attending a primary care
      clinic in Malaysia.
AB  - INTRODUCTION: Anxiety is a common mental health disorder in primary care, with a
      higher prevalence among women compared to men. AIM: This is the first study to
      validate the Generalised Anxiety Disorder-7 questionnaire (GAD-7) as a case
      finding instrument for anxiety in a primary care setting in Malaysia. The
      objective was to determine the diagnostic accuracy of the Malay version of the
      GAD-7 in detecting anxiety among women. METHODS: This cross-sectional study was
      conducted in a government-funded primary care clinic in Malaysia. Consecutive
      women participants attending the clinic during data collection were given self
      administered questionnaires including the GAD-7 (Malay version). Participants
      then were selected using systematic weighted random sampling for Composite
      International Diagnostic Interviews (CIDI). The GAD-7 was validated against the
      CIDI reference standard. RESULTS: The response rate was 87.5% for the
      questionnaire completion (895/1023), and 96.8% for diagnostic interviews
      (151/156). The prevalence of anxiety was 7.8%. The GAD-7 had a sensitivity of 76%
      (95% CI 61%-87%), a specificity of 94% (88%-97%), positive LR 13.7 (6.2-30.5) and
      negative LR 0.25 (0.14-0.45). DISCUSSION: The Malay version of the GAD-7 was
      found to be valid and reliable in case-finding for anxiety in this study. Due to
      its brevity, it is a suitable case-finding instrument for detecting anxiety in
      primary care settings in Malaysia.

PMID- 22377545
TI  - What contributes to delays? The primary care determinants of immunisation
      timeliness in New Zealand.
AB  - INTRODUCTION: Delay in receipt of the first vaccine dose in the primary series is
      one of the strongest and most consistent predictors of subsequent incomplete
      immunisation. AIM: To describe the on-time immunisation delivery of New Zealand
      infant scheduled vaccines by primary care practices and identify characteristics
      of practices, health professionals and patients associated with delays in receipt
      of infant immunisations. METHODS: Timeliness of immunisation delivery and factors
      associated with timely immunisation were examined in 124 randomly selected
      primary care practices in two large regions of New Zealand. RESULTS: A multiple
      regression model of demographic, practice, nurse, doctor and caregiver
      association explained 68% of the variance in immunisation timeliness between
      practices. Timeliness was higher in practices without staff shortages (beta
      coefficient -0.0770, p= 0.01), where nurses believed parental apathy (beta
      coefficient 0.0819, p=0.008) or physicians believed parental access (beta
      coefficient 0.109, p=0.002) was a barrier, and lower in practices with Maori
      governance (beta-coefficient -0.0868, p=0.05), higher social deprivation (beta
      coefficient -0.0643, <0.001) and where caregivers received immunisation
      discouraging information (beta-coefficient -0.0643, p=0.04). DISCUSSION:
      Interventions supporting practice teams and providers in primary care settings
      could produce significant improvements in immunisation timeliness.

PMID- 22377546
TI  - Why are there gaps in our management of those with high cardiovascular risk?
AB  - INTRODUCTION: Multiple New Zealand and other international studies have
      identified gaps in the management of those identified at high risk of a future
      cardiovascular (CV) event. This study sought to explore the views of health
      professionals about the barriers and facilitators present within the current
      primary health care system to the optimal management of those at high CV risk.
      METHODS: This qualitative study utilised a focus group methodology to examine the
      barriers and facilitators within primary health care (PHC), and employed a
      general inductive approach to analyse the text data. FINDINGS: The analysis of
      text data resulted in the emergence of interrelated themes, underpinned by
      subthemes. The patient, their circumstances and their characteristics and
      perceptions provided the first key theme and subthemes. The next key theme was
      primary health care providers, with subthemes of communication and values and
      beliefs. The general practice was the third theme and included multiple
      subthemes: implementation planning and pathway development, time and workload and
      roles and responsibilities. The final main theme was the health system with the
      subthemes linking to funding and leadership. CONCLUSION: This study determined
      the factors that act as barriers and facilitators to the effective management of
      those at high CV risk within the New Zealand PHC sector. General practice has a
      pivotal role in preventive health care, but to succeed there needs to be a
      refocusing of the PHC sector, requiring support from policy makers, District
      Health Boards and Primary Health Organisations, as well as those working in the
      sector.

PMID- 22377547
TI  - Community participation in primary care: what does it mean 'in practice'?
AB  - INTRODUCTION: The New Zealand 2001 Primary Health Care Strategy requires primary
      health organisations (PHOs) to involve communities in their governance and be
      responsive to communities' needs. It is less clear what the implications of this
      policy are for general practices. This paper presents key findings from a
      national study undertaken in the wake of the 2001 primary care reforms on the
      purpose and process of involving communities in primary health care. METHODS: A
      three-part qualitative process was employed. Initially, key informant interviews
      were undertaken with a diverse range of primary care policy makers, funders,
      practitioners and community stakeholders (n=42). A draft framework for involving
      communities in primary care was developed, and formed the basis of a consultation
      phase (n=26). The framework was further developed and then piloted in four PHOs
      around New Zealand. FINDINGS: Views on community participation varied among
      different stakeholder groups in the sector. Most described it as a complex
      process of relationship-building over time, and one that is quite distinct from
      consumer feedback processes in general practice. For community representatives,
      it was a process of trust-building and information-sharing between communities
      and health professionals. These relationships enabled people to feel comfortable
      seeking care, and professionals to mould services to people's needs. CONCLUSION:
      This research highlights that community is much more than a setting of care. As
      citizens, members of disadvantaged communities are partners with general
      practices and PHOs, working with them to improve health equity by ensuring that
      services are responsive to their needs.

PMID- 22377548
TI  - Reasons for non-attendance: audit findings from a nurse-led clinic.
AB  - BACKGROUND AND CONTEXT: Evidence has shown that non-attendance at clinics occurs
      for a variety of reasons and impacts negatively on client outcomes and effective
      use of clinic resources. This paper reports an audit of non-attendance at Care
      Plus and diabetes clinics undertaken between October 2007 and October 2008, in a
      large general practice in the Wellington region. ASSESSMENT OF PROBLEM: A
      retrospective and prospective audit of the non-attendance rate at nurse-led
      wellness clinics was completed using the Query Builder function in Medtech32,
      collecting data from 142 people who did not attend a scheduled appointment.
      RESULTS: Thirty-three people were unable to be contacted about their reason for
      not attending. Of those contacted, 68 did not attend because they were unaware of
      the appointment, confused regarding the appointment time, or simply forgot.
      Eighty-four people were aged between 18 and 65 years, yet of those contacted,
      only four cited work had prevented their attendance at the clinic. Difficulty
      with transport was reported by only two people. STRATEGIES FOR IMPROVEMENT: The
      audit highlighted the importance of administration processes for scheduling
      routine appointments and reminding patients about appointments. It provided
      evidence that administrative support for nurse-led clinics is necessary. LESSONS:
      Involvement in clinical audit was a new experience for many of the staff and the
      usefulness of the findings led to more positive views about how audit can be
      used. The importance of appropriate administrative support was highlighted.
      Lessons learned for future audits included the importance of a complete data set
      and consistent use of codes for data entry.

PMID- 22377549
TI  - Does a clinical guideline change chlamydia testing? Report from the Waikato
      Chlamydia Project.
AB  - BACKGROUND AND CONTEXT: Waikato District Health Board was one of three districts
      chosen to implement a national chlamydia management guideline, with the aim of
      optimising testing and treatment. Previous New Zealand studies suggest any test
      increases associated with such an intervention may be short-lived. ASSESSMENT OF
      PROBLEM: District-wide chlamydia test volumes were compared for three periods,
      before (June-Nov 2008), during (June-Nov 2009) and after (June-Nov 2010)
      guideline implementation by age, gender and ethnicity. Crude estimates of
      population test uptake were calculated. Azithromycin pharmacy claim volumes were
      assessed as a measure of treatment. RESULTS: Chlamydia test uptake for women was
      already high, with 23% of 15- to 24-year-old women tested during the period from
      June to November 2008. Although tests from under-25-year-olds increased during
      implementation in 2009, the change was not significant and was not sustained in
      2010, p=0.06. Similarly, there were no significant sustained changes by gender or
      ethnicity following implementation. STRATEGIES FOR IMPROVEMENT: This includes a
      continued emphasis on optimal chlamydia case finding and treatment by focusing on
      those at greater risk of infection. Efforts to improve partner notification
      should be instigated which may in turn better engage men around sexual health.
      LESSONS: Local data should be used to identify local issues. There is a need to
      determine whether <25 years is the optimal age threshold for targeted chlamydia
      testing in New Zealand and to ensure appropriate resources, training and support
      are in place for primary care nurses who play a pivotal role in sexual health
      care delivery.

PMID- 22377550
TI  - How to use interpreters in general practice: the development of a New Zealand
      toolkit.
AB  - BACKGROUND AND CONTEXT: New Zealand is becoming more ethnically diverse, with
      more limited English proficiency (LEP) people. Consequently there are more
      primary care consultations where patients have insufficient English to
      communicate adequately. Because effective communication is essential for good
      care, interpreters are needed in such cases. ASSESSMENT OF PROBLEM: The
      literature on the use of interpreters in health care includes the benefits of
      using both trained interpreters (accuracy, confidentiality, ethical behaviour)
      and untrained interpreters (continuity, trust, patient resistance to
      interpreter). There is little research on the actual pattern of use of
      interpreters. RESULTS: Our research documented a low use of trained interpreters,
      despite knowledge of the risks of untrained interpreters and a significant use of
      untrained interpreters where clinicians felt that the communication was
      acceptable. A review of currently available guidelines and toolkits showed that
      most insist on always using a trained interpreter, without addressing the cost or
      availability. None were suitable for direct use in New Zealand general practice.
      STRATEGIES FOR IMPROVEMENT: We produced a toolkit consisting of flowcharts,
      scenarios and information boxes to guide New Zealand practices through the
      structure, processes and outcomes of their practice to improve communication with
      LEP patients. This paper describes this toolkit and the links to the evidence,
      and argues that every consultation with LEP patients requires clinical judgement
      as to the type of interpreting needed. LESSONS: Primary care practitioners need
      understanding about when trained interpreters are required.

PMID- 22377551
TI  - General practice should only employ staff who are smoke-free: Yes.

PMID- 22377552
TI  - General practice should only employ staff who are smoke-free: No.

PMID- 22377553
TI  - Front-line health workers: leading the frontiers of change.

PMID- 22377554
TI  - 'Woe is me!': New Zealand's non-punitive regulatory environment.

PMID- 22377555
TI  - Should New Zealand introduce mandatory reporting by general practitioners of
      suspected child abuse? NO.

PMID- 22377556
TI  - Does mandatory reporting really help child protection? The view of a mandated
      Australian.

PMID- 22377557
TI  - Reducing the burden associated with bureaucratic practice in primary care: a
      welcome move by PHARMAC.

PMID- 22377558
TI  - Consider loneliness with depressed older adults.

PMID- 22377559
TI  - Vascular risk factors, white matter hyperintensities and hippocampal volume in
      normal elderly individuals.
AB  - BACKGROUND/AIMS: Hippocampal atrophy has been identified as marker for the
      development of Alzheimer's dementia (AD). To what extent vascular risk factors
      and white matter hyperintensities (WMH) affect hippocampal volume (HV) in
      asymptomatic elderly subjects and thus may impact such a predictive capacity is
      controversial. METHODS: We analysed 287 participants of the Austrian Stroke
      Prevention Study (mean age 66.6 +/- 6.6 years) with a Mini Mental State
      Examination score >=27 who were free of neuropsychiatric disease and had
      undergone MRI including coronal T(1)-weighted sequences allowing for semi
      automatic assessment of HV. Global brain volume (BV) was measured using SIENAX.
      WMH were rated according to the Fazekas scale and segmented to obtain WMH
      volumes. RESULTS: Higher age was associated with lower absolute and normalized
      HV, a lower BV and higher WMH volume. None of the vascular risk factors had an
      impact on HV except for high-density lipoprotein. This effect disappeared after
      normalization of HV. WMH severity and volume did not affect HV either.
      CONCLUSION: Our data indicate HV loss in parallel with the whole brain and
      suggest no specific vulnerability towards vascular risk factors or age-related
      WMH in a cognitively intact normal elderly population. This also supports the
      utility of HV measurements to identify impending AD.

PMID- 22377560
TI  - Thiol-promoted catalytic synthesis of diphenolic acid with sulfonated
      hyperbranched poly(arylene oxindole)s.
AB  - Acid-catalyzed condensation of levulinic acid and phenol into high yields of
      diphenolic acid (>50%) is possible with a combination of sulfonated hyperbranched
      polymers and thiol promotors, either added as a physical mixture or bound to the
      polymer by ion-pairing.

PMID- 22377561
TI  - Trastuzumab decreases the incidence of clinical relapses in patients with early
      breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating
      tumor cells: results of a randomized phase II study.
AB  - BACKGROUND: Since the detection of circulating tumor cells (CTCs) which express
      HER2 is an adverse prognostic factor in early breast cancer patients, we
      investigated the effect of trastuzumab on patients' clinical outcome. PATIENTS
      AND METHODS: Seventy five women with HER2 (-) breast cancer and detectable CK19
      mRNA-positive CTCs before and after adjuvant chemotherapy, were randomized to
      receive either trastuzumab (n=36) or observation (n=39). CK19 mRNA-positive CTCs
      were detected by RT-PCR and double stained CK(+)/HER2(+) cells by
      immunofluorescence. The primary endpoint was the 3-year disease-free survival
      rate. RESULTS: Fifty-one (89%) of the 57 analyzed patients had HER2-expressing
      CTCs. After trastuzumab administration, 27 of 36 (75%) women became CK19 mRNA
      negative compared to seven of 39 (17.9%) in the observation arm (p=0.001). After
      a median follow up time of 67.2 months, four (11%) and 15 (38%) relapses were
      observed in the trastuzumab and observation arm, respectively (p=0.008); subgroup
      analysis indicated that this effect was mainly confined to women with >3 involved
      axillary lymph nodes (p=0.004). The median DFS was also significantly higher for
      the trastuzumab-treated patients (p=0.008). CONCLUSION: Administration of
      trastuzumab can eliminate chemotherapy-resistant CK19 mRNA-positive CTCs, reduce
      the risk of disease recurrence and prolong the DFS.

PMID- 22377562
TI  - Resumption or persistence of menstruation after cytotoxic chemotherapy is a
      prognostic factor for poor disease-free survival in premenopausal patients with
      early breast cancer.
AB  - BACKGROUND: We investigated the relationship between resumption or persistence of
      menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in
      premenopausal patients with early breast cancer. METHODS: Medical records from
      872 patients who received cytotoxic chemotherapy for stage I to III breast cancer
      were retrospectively reviewed. RESULTS: The median patient age was 41 years
      (range, 21-54) and the median follow-up duration was 6.2 years (range, 0.7-10.4).
      Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and
      the majority of these received tamoxifen therapy after completing chemotherapy.
      The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n
      = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%)
      patients had persistent menstruation without CIA. DFS was significantly affected
      by younger age at diagnosis (<=35 years) (P = 0.013), tumor size > 2 cm (P <
      0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity
      (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence
      interval (CI) 1.2-2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI
      1.4-3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0-4.7, P <
      0.001), and RM (hazard ratio 1.8, 95% CI 1.2-2.7, P = 0.004) remained significant
      factors for DFS on multivariate analysis. CONCLUSIONS: A considerable proportion
      of premenopausal patients treated with chemotherapy experienced RM after CIA. RM
      was a poor prognostic factor for DFS in premenopausal patients with early breast
      cancer.

PMID- 22377563
TI  - A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized
      multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule,
      tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine
      kinase inhibitor monotherapy.
AB  - BACKGROUND: Recurrent platinum-resistant ovarian cancer usually has a poor
      outcome with conventional chemotherapeutic therapy and new treatment modalities
      are warranted. This phase II study was conducted to evaluate sunitinib, an oral
      antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting. MATERIAL
      AND METHODS: The primary end point of this randomized phase II trial was the
      objective response rate according to RECIST criteria and/or Gynecologic Cancer
      InterGroup CA125 response criteria to sunitinib in patients with recurrent
      platinum-resistant ovarian cancer who were pretreated with up to three
      chemotherapies. A selection design was employed to compare two schedules of
      sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days
      off drug; and arm 2: 37.5 mg sunitinib administered daily continuously). RESULTS:
      Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous
      treatment arm (arm 1) and 37 patients were randomly allocated to the continuous
      treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We
      observed six responders (complete response + partial response) in arm 1 (16.7%)
      and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1:
      4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall
      survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed
      no significant difference. Adverse events included fatigue as well as
      cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic
      laboratory abnormalities. Pattern and frequency of adverse events revealed no
      substantial differences between both treatment groups. CONCLUSIONS: Sunitinib
      treatment is feasible and moderately active in relapsed platinum-resistant
      ovarian cancer. The noncontinuous treatment schedule should be chosen for further
      studies in ovarian cancer.

PMID- 22377564
TI  - Risk of serious toxicity in 1181 patients treated in phase I clinical trials of
      predominantly targeted anticancer drugs: the M. D. Anderson Cancer Center
      experience.
AB  - BACKGROUND: This study assessed toxicity in advanced cancer patients treated in a
      phase I clinic that focuses on targeted agents. PATIENTS AND METHODS: An analysis
      of database records of 1181 consecutive patients with advanced cancer who were
      treated in the phase I program starting 1 January 2006 was carried out. RESULTS:
      All patients were treated on at least 1 of the 82 phase I clinical trials.
      Overall, 56 trials (68.3%) had only targeted agents, 13 (15.9%) only cytotoxics,
      and 13 (15.9%) targeted and cytotoxic agents. Rates of grade 3 and 4 toxicity
      that were at least possibly drug related were 7.1% and 3.2%, respectively, and 5
      of the 1181 patients (0.4%) died from toxicity that was at least possibly drug
      related. The most common grade 3 or more toxic effects were neutropenia,
      thrombocytopenia, anemia, dehydration, infection, altered mental status,
      bleeding, vomiting, nausea, and diarrhea. Eastern Cooperative Oncology Group
      (ECOG) performance status greater than zero and use of a cytotoxic agent were
      selected as independent factors associated with serious toxicity. CONCLUSION:
      Phase I trials of primarily targeted agents showed low rates of toxicity, with
      10.3% of patients experiencing grade 3 or 4 toxicity and a 0.4% rate of death, at
      least possibly drug related.

PMID- 22377565
TI  - Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and
      benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.
AB  - BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many
      prognostic biomarkers have been tested, but most studies included heterogeneous
      patients. We aimed to investigate the prognostic and/or predictive values of four
      relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A
      total of 471 patients who had resected pancreatic adenocarcinoma were included.
      Using tissue microarray, we assessed the relationship of biomarker expressions
      with the overall survival: Smad4, type II TGF-beta receptor, CXCR4, and LKB1.
      RESULTS: High CXCR4 expression was found to be the only independent negative
      prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was
      significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001)
      and was the strongest prognostic factor compared with clinicopathological
      factors. In patients who did not received adjuvant treatment, there was a trend
      toward decrease in the overall survival for negative Smad4 expression. Loss of
      Smad4 expression was not correlated with recurrence pattern but was shown to be
      predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002).
      CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with
      distant metastatic recurrence and appears as an attractive target to be evaluated
      in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a
      potential predictor of adjuvant CT benefit.

PMID- 22377566
TI  - Middle lobe syndrome: a review of clinicopathological features, diagnosis and
      treatment.
AB  - Middle lobe syndrome (MLS) is a rare but important clinical entity that has been
      poorly defined in the literature. It is characterized by recurrent or chronic
      collapse of the middle lobe of the right lung but can also involve the lingula of
      the left lung. Pathophysiologically, there are two forms of MLS, namely
      obstructive and nonobstructive. Obstructive MLS is usually caused by
      endobronchial lesions or extrinsic compression of the middle lobe bronchus such
      as from hilar lymphadenopathy or tumors of neoplastic origin, resulting in
      postobstructive atelectasis and pneumonitis. In the nonobstructive type, no
      obstruction of the middle lobe bronchus is evident during bronchoscopy or with
      computerized tomography of the chest. The etiology of the nonobstructive form is
      not completely understood. Inefficient collateral ventilation, infection and
      inflammation in the middle lobe or lingula are thought to play a role, and
      bronchiectasis is the most common histological finding. Patients with proven
      endobronchial lesions or malignancy are usually offered surgical resection
      directly. This contrasts with nonobstructive MLS, where most patients respond to
      medical treatment consisting of bronchodilators, mucolytics and broad-spectrum
      antibiotics. However, some patients do not respond to conservative treatment and
      may suffer irreversible damage of the middle lobe or lingula, in addition to
      having recurrent symptoms of infection or inflammation. These selected patients
      can be offered surgical resection of the middle lobe or lingula, which is
      associated with a low mortality rate and favorable outcome.

PMID- 22377570
TI  - Executive function and suicidal risk in women with Borderline Personality
      Disorder.
AB  - A range of executive function (EF) deficits have been associated with Borderline
      Personality (BPD), a disorder characterized by high rates of suicide. However,
      the role of EF and suicide risk in BPD has not been examined. This exploratory
      study compared working memory, Stroop interference, motor inhibition (SSRT) and
      Iowa Gambling Task (IGT) decision making performance in 42 women with BPD and 41
      healthy controls. The sensitivity of EF to suicidal risk as assessed by the
      Suicide Behaviour Questionnaire-R (Osman et al., 2001) was also tested. Women
      with BPD performed similar to controls on all EF except decision making. Weaker
      Stroop interference control, however, was the only significant EF contributor to
      suicide risk, demonstrating near equivalent contributions to that of depression.
      EF and depression collectively explained 34% of the adjusted variance in total
      suicide risk. Contrary to expectations, IGT decision making and motor inhibition
      were not associated with overall suicide risk. Only Stroop interference control
      contributed significantly to lifetime suicide intent/attempt beyond depression or
      BPD severity. As prior suicide attempt remains the strongest predictor of future
      attempt (Soloff et al., 2003), the sensitivity of stroop performance to suicidal
      risk may be clinically important. Interference control may represent a
      "diathesis" for suicide that is independent of psychiatric diagnoses.

PMID- 22377571
TI  - Impact of symptom resolution on medication adherence in first episode psychosis.
AB  - Adequate adherence to medication confers benefits on patients with psychotic
      illness, but is difficult to achieve. Efficacy of medication influences adherence
      in patients in advanced phases of illness and may have a similar influence on
      patients with a first episode of psychosis (FEP). We assessed medication
      adherence and efficacy in 216 FEP patients at program entry and at 3 and 6 months
      later. "Efficacy" was evaluated as the ability of medication to reduce positive
      or negative symptoms to below established thresholds for clinical remission at
      each evaluation. Adherence was defined as adequate (>75%) or not. Resolution of
      negative symptoms by month 3 of treatment was associated with inadequate
      adherence at months 3 and 6. In contrast, rapid resolution of positive symptoms
      showed no relationship to adherence. In a multivariate analysis taking into
      account other determinants of adherence in FEP, the role of early negative
      symptom remission was confirmed, and we found that a 3-month sustained remission
      of positive symptoms was associated with adequate adherence. Medication efficacy
      may promote adherence if it produces sustained remission of positive symptoms.
      However, many patients who benefit from medication, particularly those with rapid
      improvement of negative symptoms, fail to adhere to the treatment.

PMID- 22377573
TI  - Taxometric analyses of paranoid and schizoid personality disorders.
AB  - There remains debate about whether personality disorders (PDs) are better
      conceptualized as categorical, reflecting discontinuity from normal personality;
      or dimensional, existing on a continuum of severity with normal personality
      traits. Evidence suggests that most PDs are dimensional but there is a lack of
      consensus about the structure of Cluster A disorders. Taxometric methods are
      adaptable to investigating the taxonic status of psychiatric disorders. The
      current study investigated the latent structure of paranoid and schizoid PDs in
      an epidemiological sample (N=43,093) drawn from the National Epidemiological
      Survey on Alcohol and Related Conditions (NESARC) using taxometric analyses. The
      current study used taxometric methods to analyze three indicators of paranoid PD 
      mistrust, resentment, and functional disturbance - and three indicators of
      schizoid PD - emotional detachment, social withdrawal, and functional disturbance
      - derived factor analytically. Overall, taxometrics supported a dimensional
      rather than taxonic structure for paranoid and schizoid PDs through examination
      of taxometric graphs and comparative curve fit indices. Dimensional models of
      paranoid and schizoid PDs better predicted social functioning, role-emotional,
      and mental health scales in the survey than categorical models. Evidence from the
      current study supports recent efforts to represent paranoid and schizoid PDs as
      well as other PDs along broad personality dimensions.

PMID- 22377572
TI  - Utility of self-reported sleep disturbances as a marker for major depressive
      disorder (MDD): findings from the World Mental Health Japan Survey 2002-2006.
AB  - Although major depressive disorder (MDD) is a serious common disease, many
      depressive patients seek primary care with complaints of sleep disturbances that
      remain undiagnosed. The purpose of this study was to investigate the utility of
      self-reported sleep disturbances as a marker for MDD. This study investigated the
      association between 12-month prevalence of self-reported sleep disturbances and
      MDD using data from a cross-sectional survey in Japan. The sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and the area under the receiver operating characteristic curve (AUC) of self
      reported sleep disturbances as a marker for MDD were 58.9%, 73.4%, 6.9%, 98.1%,
      and 0.66, respectively. Self-reported sleep disturbances showed highest utility
      for the youngest group. Among four types of sleep disturbances, the problem of
      daytime sleepiness was most useful as a marker for MDD. Combined with at least
      moderate role impairment, self-reported sleep disturbances became more
      informative with higher specificity (99.6%) and PPV (80.0%) as a marker for MDD.
      Self-reported sleep disturbances cannot be a marker for MDD in isolation.
      Comorbid role impairment increases the probability of MDD. Clinicians should be
      cautious in assessments of young people who have sleep disturbances. Daytime
      sleepiness should be included among the questions asked when inquiring about
      sleep disturbances.

PMID- 22377574
TI  - Young people's mental health first aid intentions and beliefs prospectively
      predict their actions: findings from an Australian National Survey of Youth.
AB  - Little is known about whether mental health first aid knowledge and beliefs of
      young people actually translate into actual behavior. This study examined whether
      young people's first aid intentions and beliefs predicted the actions they later
      took to help a close friend or family member with a mental health problem.
      Participants in a 2006 national survey of Australian youth (aged 12-25 years)
      reported on their first aid intentions and beliefs based on one of four
      vignettes: depression, depression with alcohol misuse, psychosis, and social
      phobia. At a two-year follow-up interview, they reported on actions they had
      taken to help any family member or close friend with a problem similar to the
      vignette character since the initial interview. Of the 2005 participants
      interviewed at follow-up, 608 reported knowing someone with a similar problem.
      Overall, young people's first aid intentions and beliefs about the helpfulness of
      particular first aid actions predicted the actions they actually took to assist a
      close other. However, the belief in and intention to encourage professional help
      did not predict subsequent action. Findings suggest that young people's mental
      health first aid intentions and beliefs may be valid indicators of their
      subsequent actions.

PMID- 22377575
TI  - Psychometric properties of a performance-based measurement of functional
      capacity, the UCSD Performance-based Skills Assessment - Brief version.
AB  - The UCSD Performance-based Skills Assessment - Brief version (UPSA-B) describes
      the functions of patients without negative influences of environmental factors
      such as unemployment or shortage in housing. The aim of the present study is to
      further explore the psychometric properties of the UPSA-B as well as to ensure
      that the Swedish version can be used in clinical practice and for research
      purposes. Participants were 211 patients, 135 men and 76 women, diagnosed with
      schizophrenia, schizoaffective disorder, or delusional disorder. Results indicate
      that the UPSA-B is a reliable instrument with good psychometric properties
      regarding validity and reliability. The instrument also had a capacity to reveal
      differences between various patient groups, both diagnostic groups and groups
      based on remission status. The conclusion drawn is that the UPSA-B is a valuable
      instrument that could be used in future cross-national studies to describe the
      level of functioning for patients with schizophrenia and other psychotic
      illnesses.

PMID- 22377576
TI  - Mentalizing in first-episode psychosis.
AB  - Mentalizing deficits have often been observed in people with schizophrenia and a
      few recent studies suggest that such deficits are also present in patients with
      first episode psychosis (FEP). It is not clear, however, whether these
      mentalizing deficits in FEP can be accounted for by underlying processes such as
      social cue recognition, social knowledge and general reasoning. In this study, we
      assessed mentalizing abilities in 31 people with FEP and 31 matched controls
      using a novel, comprehensive mentalizing task validated through the present
      study. We also assessed social cue recognition, social knowledge and non-social
      (or general) reasoning performance in the same participants in order to determine
      if the mentalizing deficits in FEP can be at least partly explained by
      performance in these three underlying processes. Overall, the mentalizing task
      revealed the greatest impairment in FEP, an impairment that remained significant
      even after controlling for social cue recognition, social knowledge and non
      social reasoning performance. Interestingly, non-social reasoning and social
      knowledge were both shown to contribute to mentalizing performance. In addition,
      social cognition measures were linked to social functioning in the FEP group,
      with the strongest correlation observed with mentalizing performance. Taken
      together, these results show that mentalizing is an aspect of social cognition
      that is particularly affected in FEP and might contribute to functional
      impairments in these patients. These deficits could be a prime target for
      cognitive remediation in FEP, and our results suggest that this could be done
      either directly or through improvement of related social and non-social cognitive
      skills such as social knowledge and general reasoning.

PMID- 22377577
TI  - The contribution of executive functions deficits to impaired episodic memory in
      individuals with alcoholism.
AB  - Individuals with alcoholism commonly exhibit impaired performance on episodic
      memory tasks. However, the contribution of their impaired executive functioning
      to poor episodic memory remains to be clarified. Thirty-six recently detoxified
      and sober asymptomatic alcoholic men and 36 matched non-alcoholic participants
      were tested for processing speed, prepotent response inhibition, mental
      flexibility, coordination of dual-task and a verbal episodic memory task.
      Compared with non-alcoholic individuals, the alcoholic patients showed impaired
      executive functions combined with below normal performance on both free and
      delayed recall. In contrast, processing speed, cued recall and recognition were
      preserved. Regression analyses revealed that 47% of alcoholics' episodic memory's
      free recall performance was predicted by mental flexibility and that 49% of their
      delayed recall performance was predicted by mental flexibility, manipulation of
      dual-task and prepotent response inhibition. Regarding participants' executive
      predictors of episodic memory performance, the slopes of beta coefficients were
      significantly different between the two groups, with alcoholics requiring more
      their executive system than non-alcoholics. Once detoxified, alcoholic patients
      showed episodic memory deficits mainly characterized by impaired effortful
      (executive) processes. Compared with controls, patients used effortful learning
      strategies, which are nonetheless less efficient.

PMID- 22377578
TI  - Preliminary structure and predictive value of attenuated negative symptoms in
      22q11.2 deletion syndrome.
AB  - Current research in schizophrenia suggests that negative symptoms cannot be
      considered a unitary construct and should be divided in two dimensions: lack of
      motivation and impoverishment of expression. In addition, negative symptoms are
      particularly related to decreased daily-life functioning. In the present study,
      we aimed to replicate these results in a sample of participants with 22q11.2
      deletion syndrome (22q11DS), a neurogenetic condition associated with high risk
      of developing schizophrenia. We also expected to observe an association between
      the COMT Val/Met polymorphism and negative symptoms. We examined the factorial
      structure of negative symptoms in a sample of 47 individuals with 22q11DS using
      the Structured Interview for Prodromal Symptoms (SIPS) and the Positive and
      Negative Syndrome Scale (PANSS). We also performed stepwise regression analyses
      to investigate the associations between negative symptoms, adaptive skills and
      the COMT Val/Met polymorphism. Negative symptoms were explained by a two-factor
      solution, namely the "amotivation and social withdrawal" and the "emotional
      withdrawal and expression" dimensions. The motivational dimension was
      significantly associated with daily-life functioning. Met carriers were rated as
      experiencing significantly more symptoms of amotivation. The results are
      interpreted in the light of existing cognitive models in the field of motivation
      and schizophrenia.

PMID- 22377581
TI  - Detection of mosquito-only flaviviruses in Europe.
AB  - The genus Flavivirus, family Flaviviridae, includes a number of important
      arthropod-transmitted human pathogens such as dengue viruses, West Nile virus,
      Japanese encephalitis virus and yellow fever virus. In addition, the genus
      includes flaviviruses without a known vertebrate reservoir, which have been
      detected only in insects, particularly in mosquitoes, such as cell fusing agent
      virus, Kamiti River virus, Culex flavivirus, Aedes flavivirus, Quang Binh virus,
      Nakiwogo virus and Calbertado virus. Reports of the detection of these viruses
      with no recognized pathogenic role in humans are increasing in mosquitoes
      collected around the world, particularly in those sampled in entomological
      surveys targeting pathogenic flaviviruses. The presence of six potential
      flaviviruses, detected from independent European arbovirus surveys undertaken in
      the Czech Republic, Italy, Portugal, Spain and the UK between 2007 and 2010, is
      reported in this work. Whilst the Aedes flaviviruses, detected in Italy from
      Aedes albopictus mosquitoes, had already been isolated in Japan, the remaining
      five viruses have not been reported previously: one was detected in Italy,
      Portugal and Spain from Aedes mosquitoes (particularly from Aedes caspius), one
      in Portugal and Spain from Culex theileri mosquitoes, one in the Czech Republic
      and Italy from Aedes vexans, one in the Czech Republic from Aedes vexans and the
      last in the UK from Aedes cinereus. Phylogenetic analysis confirmed the close
      relationship of these putative viruses to other insect-only flaviviruses.

PMID- 22377579
TI  - Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and
      description of new cases.
AB  - An extensive variety of THAP1 sequence variants have been associated with focal,
      segmental and generalized dystonia with age of onset ranging from 3 to over 60
      years. In previous work, we screened 1114 subjects with mainly adult-onset
      primary dystonia (Neurology 2010; 74:229-238) and identified 6 missense mutations
      in THAP1. For this report, we screened 750 additional subjects for mutations in
      coding regions of THAP1 and interrogated all published descriptions of THAP1
      phenotypes (gender, age of onset, anatomical distribution of dystonia, family
      history and site of onset) to explore the possibility of THAP1 genotype-phenotype
      correlations and facilitate a deeper understanding of THAP1 pathobiology. We
      identified 5 additional missense mutations in THAP1 (p.A7D, p.K16E, p.S21C,
      p.R29Q, and p.I80V). Three of these variants are associated with appendicular
      tremors, which were an isolated or presenting sign in some of the affected
      subjects. Abductor laryngeal dystonia and mild blepharospasm can be
      manifestations of THAP1 mutations in some individuals. Overall, mean age of onset
      for THAP1 dystonia is 16.8 years and the most common sites of onset are the arm
      and neck, and the most frequently affected anatomical site is the neck. In
      addition, over half of patients exhibit either cranial or laryngeal involvement.
      Protein truncating mutations and missense mutations within the THAP domain of
      THAP1 tend to manifest at an earlier age and exhibit more extensive anatomical
      distributions than mutations localized to other regions of THAP1.

PMID- 22377582
TI  - Genetic variation and recombination in Aichi virus.
AB  - Aichi virus (AiV), a member of the genus Kobuvirus in the family Picornaviridae,
      causes gastroenteritis in humans. It was noted that AiV differs from other
      picornaviruses in its unusually high C content and a very high degree of genome
      ordered RNA secondary structures. However, the genetic variability and mutational
      restrictions on a full-genome scale have not been studied. In addition to the
      available five complete AiV genomes, we determined here another five complete
      coding sequences of AiV sampled in Germany, 2004. Distinctive AiV genetic
      features included a low incidence of recombination along the genome without
      obvious hotspots or spared regions and very low rates of synonymous and non
      synonymous variation, supporting an absence of AiV serotypes. In addition, the
      absence of recombination between AiV genotypes A and B suggested the existence of
      reproductive isolation between taxonomic units below the species level. In
      contrast to most other picornaviruses, AiV genomes strongly avoided the UpA
      dinucleotide, while there was no obvious selection against the CpG dinucleotide.
      AiV genomes also appeared to contain a codon usage bias (CUB) apparent as an
      effective number of codons of 39.5, which was amongst the most extreme among RNA
      viruses. A set of sequence scrambling algorithms was developed to determine the
      origin of CUB in AiV. While in most picornaviruses the genomic dinucleotide
      content contributed significantly to CUB, in AiV its extreme nucleotide content,
      i.e. 57 % third codon position C, was the main driving force behind the apparent
      CUB.

PMID- 22377583
TI  - Virion endocytosis is a major target for murid herpesvirus-4 neutralization.
AB  - Herpesviruses consistently transmit from immunocompetent carriers, implying that
      their neutralization is hard to achieve. Murid herpesvirus-4 (MuHV-4) exploits
      host IgG Fc receptors to bypass blocks to cell binding, and pH-dependent protein
      conformation changes to unveil its fusion machinery only after endocytosis.
      Nevertheless, neutralization remains possible by targeting the virion
      glycoprotein H (gH)-gL heterodimer, and the neutralizing antibody responses of
      MuHV-4 carriers are improved by boosting with recombinant gH-gL. We analysed here
      how gH-gL-directed neutralization works. The MuHV-4 gH-gL binds to heparan
      sulfate. However, most gH-gL-specific neutralizing antibodies did not block this
      interaction; neither did they act directly on fusion. Instead, they blocked
      virion endocytosis and transport to the late endosomes, where membrane fusion
      normally occurs. The poor endocytosis of gH-gL-neutralized virions was
      recapitulated precisely by virions genetically lacking gL. Therefore, driving
      virion uptake appears to be an important function of gH-gL that provides a major
      target for antibody-mediated neutralization.

PMID- 22377584
TI  - Impact of deficiency in CCR2 and CX3CR1 receptors on monocytes trafficking in
      herpes simplex virus encephalitis.
AB  - The role played by resident microglia and by the infiltration of peripheral
      monocytes/macrophages in the innate immune response during herpes simplex virus
      type 1 (HSV-1) encephalitis was evaluated in mice deficient for the CCR2 and
      CX3CR1 receptors. CCR2(-/-), CX3CR1(-/-) and C57BL/6 wild-type (WT) male mice
      were infected intranasally with 7*10(5) p.f.u. of an HSV-1 clinical strain and
      monitored for signs of encephalitis and survival. In addition, brain viral DNA
      load and cytokine levels were evaluated by RT-PCR and magnetic bead-based
      immunoassay, respectively. The cellular response was assessed by fluorescence
      activated cell sorting of blood and brain leukocytes. Infected CX3CR1(-/-) mice
      had a significantly lower mean life expectancy than WT mice (P<0.05, log-rank
      test) and demonstrated an increased infiltration of Ly-6C(high) 'inflammatory'
      macrophages in the brain (P<0.05). Infected CCR2(-/-) mice had fewer monocytes
      (P<0.05), with a lower proportion of Ly-6C(high) 'inflammatory' monocytes in the
      blood than the other groups (P<0.05). Brain viral DNA loads were only slightly
      higher in knockout mice than in WT mice (P-value not significant). These data
      suggest that CCR2 and especially CX3CR1 receptors are necessary to initiate a
      proper immune response during HSV encephalitis. More precisely, CCR2 is crucial
      for the emigration of monocytes from the bone marrow to the blood, whereas CX3CR1
      is mostly implicated in the regulation of infiltrating cells from the blood to
      the site of infection and in the control of the immune homeostasis of the brain.

PMID- 22377585
TI  - In vivo and in vitro studies on the antiviral activities of viperin against
      influenza H1N1 virus infection.
AB  - Influenza A virus has caused a number of pandemics in past decades, including the
      recent H1N1-2009 pandemic. Viperin is an interferon (IFN)-inducible protein of
      innate immunity, and acts as a broad-spectrum antiviral protein. We explored the
      antiviral activities and mechanisms of viperin during influenza virus (IFV)
      infection in vitro and in vivo. Wild-type (WT) HeLa and viperin-expressing HeLa
      cells were infected with influenza A/WSN/33/H1N1 (WSN33) virus, and subjected to
      virological, light and electron microscopic analyses. Viperin expression reduced
      virus replication and titres, and restricted viral budding. Young and old viperin
      knockout (KO) mice and WT control animals were challenged with influenza WSN33 at
      lethal doses of 10(3) and 10(4) p.f.u. via the intratracheal route. Lungs were
      subjected to histopathological, virological and molecular studies. Upon lethal
      IFV challenge, both WT and KO mice revealed similar trends of infection and
      recovery with similar mortality rates. Viral quantification assay and
      histopathological evaluation of lungs from different time points showed no
      significant difference in viral loads and lung damage scores between the two
      groups of mice. Although the in vitro studies demonstrated the ability of viperin
      to restrict influenza H1N1 virus replication, the viperin-deficient mouse model
      indicated that absence of viperin enhanced neither the viral load nor pulmonary
      damage in the lungs of infected mice. This may be due to the compensation of IFN
      stimulated genes in the lungs and/or the influenza non-structural protein 1
      mediated IFN antagonism dampening the IFN response, thereby rendering the loss of
      viperin insignificant. Nevertheless, further investigations that exploit the
      antiviral mechanisms of viperin as prophylaxis are still warranted.

PMID- 22377586
TI  - Prevalence and risk factors associated with prehypertension and hypertension in
      the Chinese She population.
AB  - BACKGROUND: Little is known about the prevalence and cardiovascular risk factors
      for prehypertension and hypertension in the She ethnic minority population of
      Fujian province in China. METHODS AND RESULTS: Between April 2009 and September
      2009, 5,523 participants of She nationality aged between 20 and 80 years
      participated in this survey and 5,357 were eventually enrolled in analyses. The
      survey was carried out to assess blood pressure and cardiovascular risk factors.
      The prevalence of prehypertension and hypertension was 35.87 and 38.42%,
      respectively, in all participants. Only 26.63% of the subjects with hypertension
      were aware of their diagnosis. Multivariate logistic regression showed that age,
      gender, overweight/obesity, dyslipidemia and alcohol use were risk factors for
      prehypertension, and age, overweight/obesity, dyslipidemia, alcohol use, family
      history of hypertension and hyperuricemia were risk factors for hypertension. The
      clustering of 2 and >= 3 risk factors was in higher proportion for subjects with
      hypertension and prehypertension when compared with those with prehypertension
      and normotension, respectively. After adjusting for other confounding factors,
      multivariable logistic regression showed that the greater the number of
      clustering cardiovascular risk factors, the greater the odds ratios for
      prehypertension and hypertension are. CONCLUSION: Hypertension and
      prehypertension were common in the She population of Fujian province.
      Cardiovascular risk factors cluster during prehypertension and awareness of
      hypertension was minimal. Early lifestyle modifications could be advocated to
      prevent the transition from prehypertension to hypertension and cardiovascular
      disease.

PMID- 22377589
TI  - On the complexation kinetics for metallization of organic layers: palladium onto
      a pyridine-terminated araliphatic thiol film.
AB  - Palladium nanoparticles have been deposited electrochemically onto self-assembled
      monolayers (SAMs) of 4-(4-(4-pyridyl)phenyl)phenylmethanethiol. A pronounced
      correlation between the kinetics of the complexation between pyridine nitrogens
      and Pd cations and the sample potential has been observed. The amount of the Pd
      deposit significantly increases by adjusting the sample potential during the
      complexation step to values below the point of zero charge. The size of the
      spherical shaped Pd nanoparticles varies within a certain limit according to the
      amount of Pd(2+) ions initially coordinated on top of the SAM. The metallic state
      of these particles was confirmed by X-ray photoelectron spectroscopy and infrared
      reflection-absorption spectroscopy. Moreover, CO adsorption on the clean Pd
      deposit revealed further information about the crystallographic orientation of
      the nanoparticles.

PMID- 22377590
TI  - Post-mastectomy pain syndrome: incidence and risks.
AB  - BACKGROUND: Post-mastectomy pain syndrome is defined as a chronic pain that
      persists beyond the normal healing time of 3 months. It is considered a
      neuropathic condition that arises after surgery for breast cancer. AIM: To
      evaluate the incidence and risk factors of pain syndromes in patients undergoing
      surgical treatment of breast cancer in the National Cancer Institute. METHODS:
      This study is a prospective cohort of women undergoing surgical treatment for
      breast cancer from September 2008 to June 2009, followed up until 6 months
      postoperatively. RESULTS AND CONCLUSIONS: One hundred seventy-four women were
      examined. The mean age was 58 years. The incidence of pain syndrome was 52%.
      Younger women (<40 years) and those who were submitted to axillary lymph node
      dissection (with more than 15 lymph nodes excised) have shown a significantly
      increased risk of pain syndrome after surgery for breast cancer (relative risk
      (RR) =5.23 95% confidence interval (CI): 1.11-24.64) and (RR=2.01 95% CI: 1.08
      3.75).

PMID- 22377592
TI  - Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro.
AB  - BACKGROUND: Extracts and essential oils of medicinal plants are increasingly of
      interest as novel drugs for antiherpetic agents, since the herpes simplex virus
      (HSV) might develop resistance to commonly used antiviral drugs. METHODS: An
      aqueous extract of Melissa officinalis as well as phenolic extract compounds,
      i.e. caffeic acid, p-coumaric acid and rosmarinic acid were examined for their
      antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. RESULTS:
      When drugs were added to HSV-1-infected cells, no antiviral effect was observed
      as determined by plaque reduction assay and analysis of expression of viral
      protein ICP0. However, the Melissa extract demonstrated a high virucidal activity
      against HSV-1, even at very low concentrations of 1.5 MUg/ml, whereas similar
      results for phenolic compounds were only achieved at 100 times higher
      concentrations. Besides the virucidal activity, the Melissa extract and
      rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent
      manner. These results indicate that rosmarinic acid was the main contributor to
      the antiviral activity of Melissa extract. However, the selectivity index of
      Melissa extract of 875 against HSV is superior to the selectivity indices of
      single constituents. CONCLUSION: Melissa extract exhibits low toxicity, is
      virucidal and affects HSV-1 attachment to host cells in vitro.

PMID- 22377591
TI  - Lifestyle factors associated with serum N-3 fatty acid levels in breast cancer
      patients.
AB  - Long chain n3 fatty acids appear to have beneficial effects in several domains of
      health relevant to breast cancer survivors. This study evaluated inter-individual
      differences in serum levels of n3 fatty acids in 40 breast cancer patients who
      were participating in a pilot study for prevention of weight gain. Significant
      predictors of baseline n3 fatty acid levels in serum were dietary intakes of n3
      fatty acids, BMI, serum levels of carotenoids and TV hours watched/day,
      accounting for 43% of the variance. Counseling for prevention of weight gain also
      tended to increase n3 fatty acid blood levels over time during chemotherapy.

PMID- 22377593
TI  - Multi-component synthesis and in vitro and in vivo anticancer activity of novel
      arylmethylene bis-isoxazolo[4,5-b]pyridine-N-oxides.
AB  - A three component one-pot protocol has been investigated for the synthesis of
      arylmethylene bis-isoxazolo[4,5-b]pyridine-N-oxides 1 from the commercially
      available materials. The title compounds 1 were also synthesized by a step-wise
      method and found to be identical with one-pot synthesis by spectral and
      analytical data. The newly synthesized compounds were evaluated for their in
      vitro anticancer activity against human cancer cell lines and in vivo anticancer
      activity on EAC-bearing mice. Compound 1a was found to be the most active both in
      in vitro and in vivo cytotoxic studies.

PMID- 22377595
TI  - Small interfering RNA specific for N-methyl-D-aspartate receptor 2B offers
      neuroprotection to dopamine neurons through activation of MAP kinase.
AB  - In the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was
      applied in parkinsonian models. Our previous results showed that reduction in
      expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl
      D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the
      6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease
      (PD).

PMID- 22377596
TI  - Postoperative intensity-modulated arc therapy for cervical and endometrial
      cancer: a prospective report on toxicity.
AB  - PURPOSE: To report on toxicity after postoperative intensity-modulated arc
      therapy (IMAT) for cervical (CC) and endometrial cancer (EC). METHODS AND
      MATERIALS: Twenty-four CC and 41 EC patients were treated with postoperative
      IMAT. If indicated, para-aortic lymph node irradiation (preventive or when
      affected, PALN) and/or concomitant cisplatin (40 mg/m(2), weekly) was
      administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy
      (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation
      related toxicity was assessed prospectively. The effect of concomitant cisplatin
      and PALN irradiation was evaluated. RESULTS: Regarding acute toxicity (n = 65),
      Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of
      patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary
      toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and
      3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen
      percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin
      toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea
      (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade >= 2
      hematologic toxicity (38% vs. nil, p = 0.003), Grade >= 2 leukopenia (33% vs.
      nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05).
      Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31%
      vs. 4%, p = 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p
      = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity
      occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue
      occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN
      irradiation increased late toxicity rates. CONCLUSIONS: Postoperative IMAT for EC
      or CC is associated with low acute and late toxicity. Concomitant chemotherapy
      and PALN irradiation influences acute but not late toxicity.

PMID- 22377597
TI  - Eating out of the hand, maggots--friend or foe?
AB  - The presence of maggots (fly larvae) in an open wound is a repelling sight to
      many and documented cases of myiasis in the literature are scant due to the
      rarity of such infestation in live patients. A unique case of such a presentation
      is elaborated in a patient who sustained a crush injury to the hand. This case
      serves to highlight the unique challenges faced in treating such injuries and to
      raise the profile of maggots and their untapped potential use in biodebridement
      and management of open wounds in modern day wound care practices.

PMID- 22377598
TI  - Managing nurses with health concerns.

PMID- 22377599
TI  - Zero HAPUs: Reaching for the moon.

PMID- 22377600
TI  - Healthcare design and IT solutions.

PMID- 22377601
TI  - The Daily Plan(r): Including patients for safety's sake.

PMID- 22377603
TI  - Roads to recovery: Drug diversion surveillance programs.

PMID- 22377604
TI  - Holding on: Caring for the professional caregiver.

PMID- 22377605
TI  - Time out! Surveying surgical barriers.

PMID- 22377606
TI  - Nursing U a new concept for nursing orientation.

PMID- 22377607
TI  - Aging workforce: Retaining valuable nurses.

PMID- 22377608
TI  - Do you speak finance?

PMID- 22377609
TI  - Reporting an incompetent nurse; identifying barriers to Magnet(r) recognition.

PMID- 22377610
TI  - Primary tuberculosis of the breast: a rare cause of a breast lump.
AB  - Primary tuberculosis (TB) of the breast is a very rare condition. We present a 50
      year-old patient who presented with primary TB of the breast. The significance of
      the radiological findings, the importance of histological diagnosis and
      treatment, and the possibility of co-existence with breast cancer are discussed.

PMID- 22377611
TI  - Unresolved, atraumatic breast hematoma: post-irradiation or secondary breast
      angiosarcoma.
AB  - Post-irradiation or secondary angiosarcoma of the breast was first described in
      the 1980s in patients treated with breast conserving therapy for cancer. The
      primary management of radiation-induced breast angiosarcoma has focused on
      surgical resection with an emphasis on achieving negative tumor margins. While
      surgery remains a key component of treatment, novel therapeutic approaches have
      surfaced. Despite such advances in treatment, prognosis remains poor.

PMID- 22377612
TI  - Mondor's disease of the breast. A retrospective review.
AB  - BACKGROUND: Mondor's disease is a rare benign clinical entity characterized by
      thrombophlebitis of the superficial veins of the anterolateral thoraco-abdominal
      wall. Although several predisposing factors have been reported, the exact
      pathogenesis remains unclear. PATIENTS AND METHODS: We retrospectively reviewed
      the medical records of all patients older than 14 years who were diagnosed with
      Mondor's disease of the breast at the Breast Cancer Surgery Unit of Army General
      Hospital over a 3-year period. RESULTS: Five cases of Mondor's disease were
      identified among 5717 breast examinations performed during the study period. In 4
      patients the disease was considered to be idiopathic. Ultrasonography established
      the diagnosis in all patients but mammography was inconclusive in two cases due
      to the presence of dense breast tissue. Four patients received symptomatic
      treatment. All patients had complete clinical resolution within 2-8 weeks of
      presentation, and they are well without any evidence of recurrence for 3 to 32
      months later. No cases were associated with breast cancer. CONCLUSIONS: Mondor's
      disease of the breast is a rare benign self-limiting clinical entity.
      Ultrasonography is the diagnostic modality of choice but mammography may be
      inconclusive in the presence of dense breast tissue. Awareness of this rare
      entity is mandatory to prevent an unnecessary biopsy whereas the patients should
      be reassured of the benign nature of this disorder. Thorough evaluation is
      however necessary to rule out an underlying breast cancer or another systemic
      disease.

PMID- 22377613
TI  - Efficacy of bronchoscopic thermal vapor ablation and lobar fissure completeness
      in patients with heterogeneous emphysema.
AB  - BACKGROUND: Bronchoscopic thermal vapor ablation (BTVA) ablates emphysematous
      tissue through a localized inflammatory response followed by contractive fibrosis
      and tissue shrinkage leading to lung volume reduction that should not be
      influenced by collateral ventilation. OBJECTIVES: To determine the correlation of
      clinical data from a trial of BTVA with fissure integrity visually assessed by
      computed tomography (CT). METHODS: We conducted a single-arm study of patients
      with upper lobe-predominant emphysema (n = 44). Patients received BTVA either to
      the right upper lobe or left upper lobe, excluding the lingula. Primary efficacy
      outcomes were forced expiratory volume in 1 s (FEV(1)) and St. George's
      Respiratory Questionnaire (SGRQ) at 6 months. Lobar volume reduction from CT was
      another efficacy outcome measurement. The fissure of the treated lobe was
      analyzed visually on preinterventional CT. Incompleteness of the small fissure,
      the upper half of the right large fissure and the whole left large fissure were
      estimated visually in 5% increments, and the relative amount of fissure
      incompleteness was calculated. Pearson correlation coefficients were calculated
      for the association between fissure incompleteness and change in efficacy
      outcomes (baseline to 6 months) of BTVA. RESULTS: A total of 38 out of 44
      patients (86%) had incompleteness in the relevant fissure. Calculated relevant
      fissure incompleteness was a mean of 13% of fissure integrity (range 0-63).
      Correlation coefficients for the association of incompleteness with outcomes were
      as follows: FEV(1) = 0.17; lung volume reduction = -0.27; SGRQ score = -0.10; 6
      min walk distance = 0.0; residual volume (RV) = -0.18, and RV/total lung capacity
      = -0.14. CONCLUSIONS: Lobar fissure integrity has no or minimal influence on BTVA
      induced lung volume reduction and improvements in clinical outcomes.

PMID- 22377615
TI  - The acid free asymmetric intermolecular alpha-alkylation of aldehydes in
      fluorinated alcohols.
AB  - The acid free asymmetric intermolecular alpha-alkylation of aldehydes with
      alcohols has been discovered using trifluoroethanol as solvent. This
      unprecedented system affords the enantioenriched functionalized primary alcohols
      (after NaBH(4) reduction) in high yields and good to excellent
      enantioselectivities with wide substrate scope in the absence of any acid
      additive.

PMID- 22377616
TI  - A phase II study of first-line chemotherapy with weekly carboplatin plus
      gemcitabine in advanced non-small cell lung cancer.
AB  - BACKGROUND: The efficacy and safety of weekly carboplatin (CBDCA) and gemcitabine
      (GEM) was evaluated as first-line chemotherapy with advanced non-small cell lung
      cancer (NSCLC). METHODS: 46 chemotherapy-naive patients with measurable NSCLC
      were enrolled. Patients underwent a combination chemotherapy of GEM 1,000 mg/m2
      plus CBDCA at an area under the curve of 2 on days 1 and 8 every 3 weeks.
      RESULTS: Response rate was 30% (14/46; 95% confidence interval: 17.7-45.8%). The
      median number of treatment cycles was 3 (range 1-2). Time to progressive disease
      was 19.4 weeks and the median survival was 46.3 weeks. The 1-year survival rate
      was 46.9%. The major toxicity was hematotoxicity: grade 3 or 4 neutropenia
      (58.7%) and thrombocytopenia (45.7%). There were no other severe toxicities.
      CONCLUSION: Weekly chemotherapy with CBDCA plus GEM is a well-tolerated and
      promising regimen as first-line treatment of advanced NSCLC.

PMID- 22377617
TI  - Genetic and environmental influences on residential location in the US.
AB  - We used a classical twin design and measures of neighborhood walkability and
      social deprivation, using each twin's street address, to examine genetic and
      environmental influences on the residential location of 1389 same-sex pairs from
      a US community-based twin registry. Within-pair correlations and structural
      equation models estimated these influences on walkability among younger (ages 18
      24.9) and older (ages 25+) twins. Adjusting for social deprivation, walkability
      of residential location was primarily influenced by common environment with
      lesser contributions of unique environment and genetic factors among younger
      twins, while unique environment most strongly influenced walkability, with small
      genetic and common environment effects, among older twins. Thus, minimal variance
      in walkability was explained by shared genetic effects in younger and older
      twins, and confirms the importance of environmental factors in walkability of
      residential locations.

PMID- 22377618
TI  - Transcatheter aortic valve implantation in dialysis patients.
AB  - BACKGROUND/AIMS: Transcatheter aortic valve implantation (TAVI) has emerged as a
      new therapeutic option for high-risk patients. However, dialysis patients were
      excluded from all previous studies. The aim of this study is to compare the
      outcomes of TAVI for dialysis patients with those for patients with chronic
      kidney disease (CKD) stages 3 and 4 and to compare TAVI with open surgery in
      dialysis patients. METHODS: Part I: comparison of 10 patients on chronic
      hemodialysis with 116 patients with non-dialysis-dependent CKD undergoing TAVI.
      Part II: comparison of transcatheter (n = 15) with open surgical (n = 24) aortic
      valve replacement in dialysis patients. RESULTS: Part I: dialysis patients were
      significantly younger (72.3 vs. 82.0 years; p < 0.01). Hospital stay was
      significantly longer in dialysis patients (21.8 vs. 12.1 days; p = 0.01). Overall
      30-day mortality was 3.17%, with no deaths among dialysis patients. Six-month
      survival rates were similar (log-rank p = 0.935). Part II: patient age was
      comparable (66.5 vs. 69.5 years; p = 0.42). Patients in the surgical group tended
      to stay longer in hospital than TAVI patients (29.5 vs. 22.5 days; p = 0.35).
      CONCLUSION: TAVI is a safe procedure in patients on chronic hemodialysis. Until
      new data become available, we find no compelling reason to refuse these patients
      TAVI.

PMID- 22377619
TI  - Inflammation-induced protein carbonylation contributes to poor prognosis for
      cholangiocarcinoma.
AB  - Carbonylation is an irreversible and irreparable protein modification induced by
      oxidative stress. Cholangiocarcinoma (CCA) is associated with chronic
      inflammation caused by liver fluke infection. To investigate the relationship
      between protein carbonylation and CCA progression, carbonylated proteins were
      detected by 2D OxyBlot and identified by MALDI-TOF/TOF analyses in pooled CCA
      tissues in comparison to adjacent nontumor tissues and normal liver tissues. We
      identified 14 highly carbonylated proteins in CCA tissues. Immunoprecipitation
      and Western blot analyses of individual samples confirmed significantly greater
      carbonylation of serotransferrin, heat shock protein 70-kDa protein 1 (HSP70.1),
      and alpha1-antitrypsin (A1AT) in tumor tissues compared to normal tissues. The
      oxidative modification of these proteins was significantly associated with poor
      prognoses as determined by the Kaplan-Meier method. LC-MALDI-TOF/TOF mass
      spectrometry identified R50, K327, and P357 as carbonylated sites in
      serotransferrin, HSP70.1, and A1AT, respectively. Moreover, iron accumulation was
      significantly higher in CCA tissues with, compared to those without, carbonylated
      serotransferrin. We conclude that carbonylated serotransferrin-associated iron
      accumulation may induce oxidative stress via the Fenton reaction, and the
      carbonylation of HSP70.1 with antioxidative property and A1AT with protease
      inhibitory capacity may cause them to become dysfunctional, leading to CCA
      progression.

PMID- 22377620
TI  - FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab
      in mantle cell lymphoma: is FTY720 the next autophagy-blocking agent in lymphoma
      treatment?
AB  - Inhibition of the autophagic pathway has recently revealed promising results in
      increasing pro-death activity of multiple cancer therapeutics. Here, we discuss
      our findings regarding the autophagy-blocking and anti-neoplastic effects of a
      synthetic sphingosine analog, FTY720, in mantle cell lymphoma (MCL). We also
      emphasize how FTY720 enhances the pro-death activity of the fully humanized
      monoclonal antibody milatuzumab by inhibiting the autophagy-lysosome dependent
      degradation of its therapeutic target, CD74. Our results provide justification
      for further evaluation of FTY720 and milatuzumab as a combination therapy for
      this aggressive B-cell malignancy.

PMID- 22377621
TI  - Autophagy inhibition promotes defective neosynthesized proteins storage in ALIS,
      and induces redirection toward proteasome processing and MHCI-restricted
      presentation.
AB  - A significant portion of newly synthesized protein fails to fold properly and is
      quickly degraded. These defective ribosomal products (DRiPs) are substrates for
      the ubiquitin-proteasome system (UPS) and give rise to a large fraction of
      peptides presented by major histocompatibility complex class I molecules (MHCI).
      Here, we showed that DRiPs are also autophagy substrates, which accumulate upon
      autophagy inhibition in aggresome-like-induced structures (ALIS). Aggregation is
      critically depending on p62/SQSTM1, but occurs in the absence of activation of
      the NRF2 signaling axis and transcriptional regulation of p62/SQSTM1. We
      demonstrated that autophagy-targeted DRiPs can become UPS substrates and give
      rise to MHCI presented peptides upon autophagy inhibition. We further
      demonstrated that autophagy targeting of DRiPs is controlled by NBR1, but not
      p62/SQSTM1, CHIP or BAG-1. Active autophagy therefore directly modulates MHCI
      presentation by constantly degrading endogenous defective neosynthesized
      antigens, which are submitted to at least two distinct quality control
      mechanisms.

PMID- 22377623
TI  - [Unilateral lung opacity].

PMID- 22377624
TI  - Angiographic and histological results following implantation of a novel stent-on
      a-wire in the animal model.
AB  - AIMS: The Svelte Stent-On-A-Wire (SOAW) is a thin strut novel device consisting
      of a balloon-expandable cobalt-chromium stent premounted onto a single lumen
      fixed-wire delivery catheter platform. We evaluated the performance of the novel
      Svelte SOAW in comparison with the MultiLink Vision (ML Vision) balloon
      expandable stent, in porcine coronary arteries. METHODS AND RESULTS: Eight
      Yorkshire swine (30-day follow-up cohort) and eight Yucatan mini-swine (90-day
      follow-up cohort) were implanted with either Svelte or control ML Vision. Acute
      performance characteristics were graded by interventionalists during
      implantation. Angiographic assessments were performed at the index procedure and
      at 30 or at 90 days post implantation. Scanning electron microscopy (SEM),
      histological and histomorphometric analysis of stented segments were performed
      after angiographic follow-up. Acute implantation performance was similar between
      the two stents; however, deflation time was significantly lower in the Svelte
      stent group (Svelte 4.70+/-0.93 s vs. ML Vision 9.56+/-0.96 s, p <0.05).
      Angiographic late loss was similar for both stents at 30 (Svelte 0.83+/-0.59 mm
      vs. ML Vision 0.88+/-0.71 mm, p=0.969) and at 90 days (Svelte 0.76+/-0.35 mm vs.
      ML Vision 0.83+/-0.35 mm, p=0.679). SEM analysis showed complete
      endothelialisation at 30 days in both stent types. Histopathological assessment
      demonstrated minimal injury and inflammation at 30 and 90 days with Svelte and ML
      Vision stents as well as similar endothelialisation, neointimal maturation,
      adventitial fibrosis and neointimal fibrin. No evidence of in-stent thrombus was
      reported in either stent group. Histomorphometric analysis showed no differences
      between the two groups in lumen, stent, media or neointimal areas at either 30 or
      90 days post implantation. CONCLUSIONS: At 30 and 90 days after implantation in
      porcine coronary arteries, the Svelte Stent-On- A-Wire showed vascular healing
      and tissue response equivalent to that observed with ML Vision stent.

PMID- 22377625
TI  - Seasonal changes in composition, fatty acid, cholesterol and mineral content of
      six highly commercial fish species of Greece.
AB  - Changes in lipid, protein, ash and moisture, quantitative distribution of fatty
      acids, cholesterol and mineral content (Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni and Zn) of
      six common fish species from Greece were studied. The proximate composition of
      all samples was significantly influenced by the fishing period, even the cultured
      ones. The sum of C20:5omega-3 and C22:6omega-3 ranged from 1.18 to 2.76 for
      sardine, from 0.37 to 1.99 for bogue, from 1.1 to 1.52 for mackerel, from 1.23 to
      1.46 for sea bass, from 1.00 to 1.24 for trout and from 0.26 to 0.45 g/100 g
      edible portion for hake samples. Besides the ratio of omega-3/omega-6
      polyunsaturated fatty acids ranged from 6.80 to 19.00 for the wild fish samples
      and from 1.01 to 3.67 for the cultured ones. Cholesterol of sardine, bogue,
      mackerel, trout and sea bass ranged from 37 up to 76 mg/100 g edible flesh, while
      it was varied from 72 to 124 mg/100 g in the flesh of hake. The concentration of
      minerals was detected at acceptable levels. All fish samples seemed to be quite
      good sources of Mg, Zn and Fe. Co was not detected in the samples studied.

PMID- 22377626
TI  - Amino acids and volatile compounds in wines from Cabernet Sauvignon and
      Tempranillo varieties subjected to malolactic fermentation in barrels.
AB  - The aim of the present paper is to compare the behaviour of industrial lactic
      bacteria and indigenous bacteria of the cellar when malolactic fermentation was
      carried out in barrels. The effects of these bacteria on the concentration of
      metabolised amino acids during malolactic fermentation and on the composition of
      volatile compounds both before and after malolactic fermentation are studied. The
      experiment was performed with wines of the Tempranillo and Cabernet Sauvignon
      varieties. An analysis has been made of the easily extractable volatile compounds
      of the wood and the compounds from the grapes, and the action of the yeasts
      during the alcoholic fermentation. Acetoin and diacetyl decreased during the
      malolactic fermentation in barrels and the concentrations of furfural and its
      derivatives were up to 100 times higher in wines not subjected to malolactic
      fermentation. Most of the volatile phenols increased during the malolactic
      fermentation in wines of the Tempranillo variety, while only guaiacol (p < 0.05)
      and t-isoeugenol increased in the Cabernet Sauvignon wines. The decrease in amino
      acids during the malolactic fermentation depends much more on the variety than on
      the bacterial strain which carries out the malolactic fermentation.

PMID- 22377627
TI  - Administration of poly[di(sodium carboxylatoethylphenoxy)]phosphazene (PCEP) as
      adjuvant activated mixed Th1/Th2 immune responses in pigs.
AB  - The selection of an optimal adjuvant to enhance the potency and longevity of
      antigen specific immune responses has always been imperative for the development
      of more effective and safer vaccines. A balanced type of immune enhancing ability
      of a new adjuvant known as polyphosphazene (PCEP) has been demonstrated in mice.
      In the present study we have compared the humoral and cellular immune responses
      to vaccine formulations containing Actinobacillus pleuropneumoniae outer membrane
      antigen (OmlA) with PCEP or Emulsigen as adjuvants. Our data showed a significant
      improvement and a shift toward more balanced immune responses when OmlA antigen
      was formulated with PCEP and CpG ODN. Moreover, in contrast to Emulsigen,
      immunization with PCEP did not result in local injection site reactions
      highlighting its potential as a safe and effective adjuvant for pigs. Further,
      the ease of formulation, administration and relatively low per dose cost of PCEP
      make it a promising adjuvant for pigs.

PMID- 22377628
TI  - Prospective study of the role of inflammation in renal cancer.
AB  - BACKGROUND: The local and systemic inflammatory responses provide prognostic
      information in cancer. The modified Glasgow Prognostic Score (mGPS) provides
      additional prognostic information than C-reactive protein (CRP) alone when
      assessing the systemic inflammation in cancer. The aim of this study was to
      determine the role of local and systemic inflammation in renal cancer. METHODS:
      The cohort consisted of 79 patients who had undergone potential curative
      resection. Systemic inflammation, mGPS, was constructed by measuring preoperative
      CRP and albumin concentrations and the Klintrup-Makinen score was evaluated
      histologically for the local inflammatory response. Pathological parameters such
      as T stage, grade and tumour necrosis were also assessed. The local inflammatory
      response was assessed by examining all inflammatory cells at the tumour edge on
      diagnostic haematoxylin and eosin slides. RESULTS: On univariate analysis, T
      stage (p < 0.001), grade (p = 0.044) and mGPS (p < 0.001) were significant
      predictors of cancer-specific survival. On multivariate analysis, mGPS (hazard
      ratio 8.64, 95% confidence interval 3.5-21.29, p < 0.001) was the only
      significant independent predictor of cancer-specific survival. CONCLUSION: A
      preoperative systemic inflammatory response as measured by the mGPS is an
      independent predictor of poor cancer-specific survival in renal cancer in
      patients undergoing potential curative resection.

PMID- 22377629
TI  - The role of background selection in shaping patterns of molecular evolution and
      variation: evidence from variability on the Drosophila X chromosome.
AB  - In the putatively ancestral population of Drosophila melanogaster, the ratio of
      silent DNA sequence diversity for X-linked loci to that for autosomal loci is
      approximately one, instead of the expected "null" value of 3/4. One possible
      explanation is that background selection (the hitchhiking effect of deleterious
      mutations) is more effective on the autosomes than on the X chromosome, because
      of the lack of crossing over in male Drosophila. The expected effects of
      background selection on neutral variability at sites in the middle of an X
      chromosome or an autosomal arm were calculated for different models of chromosome
      organization and methods of approximation, using current estimates of the
      deleterious mutation rate and distributions of the fitness effects of deleterious
      mutations. The robustness of the results to different distributions of fitness
      effects, dominance coefficients, mutation rates, mapping functions, and
      chromosome size was investigated. The predicted ratio of X-linked to autosomal
      variability is relatively insensitive to these variables, except for the mutation
      rate and map length. Provided that the deleterious mutation rate per genome is
      sufficiently large, it seems likely that background selection can account for the
      observed X to autosome ratio of variability in the ancestral population of D.
      melanogaster. The fact that this ratio is much less than one in D. pseudoobscura
      is also consistent with the model's predictions, since this species has a high
      rate of crossing over. The results suggest that background selection may play a
      major role in shaping patterns of molecular evolution and variation.

PMID- 22377630
TI  - Ribosome deficiency protects against ER stress in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, 59 of the 78 ribosomal proteins are encoded by
      duplicated genes that, in most cases, encode identical or very similar protein
      products. However, different sets of ribosomal protein genes have been identified
      in screens for various phenotypes, including life span, budding pattern, and drug
      sensitivities. Due to potential suppressors of growth rate defects among this set
      of strains in the ORF deletion collection, we regenerated the entire set of
      haploid ribosomal protein gene deletion strains in a clean genetic background.
      The new strains were used to create double deletions lacking both paralogs,
      allowing us to define a set of 14 nonessential ribosomal proteins. Replicative
      life-span analysis of new strains corresponding to ORF deletion collection
      strains that likely carried suppressors of growth defects identified 11 new yeast
      replicative aging genes. Treatment of the collection of ribosomal protein gene
      deletion strains with tunicamycin revealed a significant correlation between slow
      growth and resistance to ER stress that was recapitulated by reducing translation
      of wild-type yeast with cycloheximide. Interestingly, enhanced tunicamycin
      resistance in ribosomal protein gene deletion mutants was independent of the
      unfolded protein response transcription factor Hac1. These data support a model
      in which reduced translation is protective against ER stress by a mechanism
      distinct from the canonical ER stress response pathway and further add to the
      diverse yet specific phenotypes associated with ribosomal protein gene deletions.

PMID- 22377631
TI  - Role of Mediator in regulating Pol II elongation and nucleosome displacement in
      Saccharomyces cerevisiae.
AB  - Mediator is a modular multisubunit complex that functions as a critical
      coregulator of RNA polymerase II (Pol II) transcription. While it is well
      accepted that Mediator plays important roles in the assembly and function of the
      preinitiation complex (PIC), less is known of its potential roles in regulating
      downstream steps of the transcription cycle. Here we use a combination of genetic
      and molecular approaches to investigate Mediator regulation of Pol II elongation
      in the model eukaryote, Saccharomyces cerevisiae. We find that ewe (expression
      without heat shock element) mutations in conserved Mediator subunits Med7, Med14,
      Med19, and Med21-all located within or adjacent to the middle module-severely
      diminish heat-shock-induced expression of the Hsf1-regulated HSP82 gene.
      Interestingly, these mutations do not impede Pol II recruitment to the gene's
      promoter but instead impair its transit through the coding region. This implies
      that a normal function of Mediator is to regulate a postinitiation step at HSP82.
      In addition, displacement of histones from promoter and coding regions, a
      hallmark of activated heat-shock genes, is significantly impaired in the med14
      and med21 mutants. Suggestive of a more general role, ewe mutations confer
      hypersensitivity to the anti-elongation drug 6-azauracil (6-AU) and one of them
      med21-impairs Pol II processivity on a GAL1-regulated reporter gene. Taken
      together, our results suggest that yeast Mediator, acting principally through its
      middle module, can regulate Pol II elongation at both heat-shock and non-heat
      shock genes.

PMID- 22377632
TI  - Evaluating the evidence for transmission distortion in human pedigrees.
AB  - Children of a heterozygous parent are expected to carry either allele with equal
      probability. Exceptions can occur, however, due to meiotic drive, competition
      among gametes, or viability selection, which we collectively term "transmission
      distortion" (TD). Although there are several well-characterized examples of these
      phenomena, their existence in humans remains unknown. We therefore performed a
      genome-wide scan for TD by applying the transmission disequilibrium test (TDT)
      genome-wide to three large sets of human pedigrees of European descent: the
      Framingham Heart Study (FHS), a founder population of European origin (HUTT), and
      a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an
      important confounder in this type of analysis. In FHS and HUTT, despite extensive
      quality control, we did not find sufficient evidence to exclude genotyping error
      in the strongest signals. In AGRE, however, many signals extended across multiple
      SNPs, a pattern highly unlikely to arise from genotyping error. We identified
      several candidate regions in this data set, notably a locus in 10q26.13
      displaying a genome-wide significant TDT in combined female and male
      transmissions and a signature of recent positive selection, as well as a paternal
      TD signal in 6p21.1, the same region in which a significant TD signal was
      previously observed in 30 European males. Neither region replicated in FHS,
      however, and the paternal signal was not visible in sperm competition assays or
      as allelic imbalance in sperm. In maternal transmissions, we detected no strong
      signals near centromeres or telomeres, the regions predicted to be most
      susceptible to female-specific meiotic drive, but we found a significant
      enrichment of top signals among genes involved in cell junctions. These results
      illustrate both the potential benefits and the challenges of using the TDT to
      study transmission distortion and provide candidates for investigation in future
      studies.

PMID- 22377633
TI  - Remarkably high rate of DNA amplification promoted by the mating-type switching
      mechanism in Schizosaccharomyces pombe.
AB  - A novel mating-type switching-defective mutant showed a highly unstable
      rearrangement at the mating-type locus (mat1) in fission yeast. The mutation
      resulted from local amplification of a 134-bp DNA fragment by the mat1-switching
      phenomenon. We speculate that the rolling-circle-like replication and homologous
      recombination might be the general mechanisms for local genome region expansion.

PMID- 22377634
TI  - A naturally thermolabile activity compromises genetic analysis of telomere
      function in Saccharomyces cerevisiae.
AB  - The core assumption driving the use of conditional loss-of-function reagents such
      as temperature-sensitive mutations is that the resulting phenotype(s) are solely
      due to depletion of the mutant protein under nonpermissive conditions. However,
      prior published data, combined with observations presented here, challenge the
      generality of this assumption at least for telomere biology: for both wild-type
      yeast and strains bearing null mutations in telomere protein complexes, there is
      an additional phenotypic consequence when cells are grown above 34 degrees . We
      propose that this synthetic phenotype is due to a naturally thermolabile activity
      that confers a telomere-specific defect, which we call the Tmp(-) phenotype. This
      prompted a re-examination of commonly used cdc13-ts and stn1-ts mutations, which
      indicates that these alleles are instead hypomorphic mutations that behave as
      apparent temperature-sensitive mutations due to the additive effects of the Tmp(
      ) phenotype. We therefore generated new cdc13-ts reagents, which are
      nonpermissive below 34 degrees , to allow examination of cdc13-depleted
      phenotypes in the absence of this temperature-dependent defect. A return-to
      viability experiment following prolonged incubation at 32 degrees , 34 degrees ,
      and 36 degrees  with one of these new cdc13-ts alleles argues that the
      accelerated inviability previously observed at 36 degrees  in cdc13-1 rad9-Delta
      mutant strains is a consequence of the Tmp(-) phenotype. Although this study
      focused on telomere biology, viable null mutations that confer inviability at 36
      degrees  have been identified for multiple cellular pathways. Thus, phenotypic
      analysis of other aspects of yeast biology may similarly be compromised at high
      temperatures by pathway-specific versions of the Tmp(-) phenotype.

PMID- 22377635
TI  - Maximum likelihood estimation of linkage disequilibrium in half-sib families.
AB  - Maximum likelihood methods for the estimation of linkage disequilibrium between
      biallelic DNA-markers in half-sib families (half-sib method) are developed for
      single and multifamily situations. Monte Carlo computer simulations were carried
      out for a variety of scenarios regarding sire genotypes, linkage disequilibrium,
      recombination fraction, family size, and number of families. A double
      heterozygote sire was simulated with recombination fraction of 0.00, linkage
      disequilibrium among dams of delta=0.10, and alleles at both markers segregating
      at intermediate frequencies for a family size of 500. The average estimates of
      delta were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal
      informative haplotypes, and the half-sib method, respectively. A multifamily EM
      algorithm was tested at intermediate frequencies by computer simulation. The
      range of the absolute difference between estimated and simulated delta was
      between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina
      50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo
      heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half
      sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods,
      respectively. There were 208,872 SNP pairs for which the sire was double
      heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and
      0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative
      haplotypes methods, respectively. Genome analyses for all possible sire genotypes
      with 829,042 tests showed that ignoring half-sib family structure leads to upward
      biased estimates of linkage disequilibrium. Published inferences on population
      structure and evolution of cattle should be revisited after accommodating
      existing half-sib family structure in the estimation of linkage disequilibrium.

PMID- 22377636
TI  - Detecting maternal-effect loci by statistical cross-fostering.
AB  - Great progress has been made in understanding the genetic architecture of
      phenotypic variation, but it is almost entirely focused on how the genotype of an
      individual affects the phenotype of that same individual. However, in many
      species the genotype of the mother is a major determinant of the phenotype of her
      offspring. Therefore, a complete picture of genetic architecture must include
      these maternal genetic effects, but they can be difficult to identify because
      maternal and offspring genotypes are correlated and therefore, partially
      confounded. We present a conceptual framework that overcomes this challenge to
      separate direct and maternal effects in intact families through an analysis that
      we call "statistical cross-fostering." Our approach combines genotype data from
      mothers and their offspring to remove the confounding effects of the offspring's
      own genotype on measures of maternal genetic effects. We formalize our approach
      in an orthogonal model and apply this model to an experimental population of
      mice. We identify a set of six maternal genetic effect loci that explain a
      substantial portion of variation in body size at all ages. This variation would
      be missed in an approach focused solely on direct genetic effects, but is clearly
      a major component of genetic architecture. Our approach can easily be adapted to
      examine maternal effects in different systems, and because it does not require
      experimental manipulation, it provides a framework that can be used to understand
      the contribution of maternal genetic effects in both natural and experimental
      populations.

PMID- 22377637
TI  - Postoperative midline shift as secondary screening for the long-term outcomes of
      surgical decompression of malignant middle cerebral artery infarcts.
AB  - Decompressive hemicraniectomy (DC) can save the lives of patients with malignant
      middle cerebral artery (MCA) infarction. We proposed that postoperative midline
      shift is important for the long-term outcome of patients with MCA infarction. We
      conducted a retrospective study of DC in 38 patients with malignant MCA
      infarction. The long-term outcome was assessed one year after surgery using the
      modified Rankin Scale (mRS) score. Patients who had midline shift less than the
      optimal diagnostic cut-off point on the fourth postoperative day were classified
      as having a successful decompression and the remaining patients were classified
      in the failed decompression group. The successful decompression group mRS score
      was 4.20+/-0.89 one year after surgery and the failed decompression group mRS
      score was 5.11+/-0.76 (p<0.0001). Successful decompression, resulting in
      postoperative midline shift of less than 5mm, was a key factor for beneficial,
      long-term functional outcomes in patients with malignant MCA infarction.

PMID- 22377638
TI  - Serum D-dimer as a predictor of mortality in patients with acute spontaneous
      intracerebral hemorrhage.
AB  - It has been found that the hemostatic system is activated following a brain
      injury. To explore the role of D-dimer in spontaneous intracerebral hemorrhage
      (ICH), this prospective study aimed to evaluate the association between serum D
      dimer concentration, clinical outcome and radiographic findings of ICH patients
      in the emergency department (ED). Patients with acute (<24 hours) spontaneous ICH
      were enrolled in this study. The D-dimer concentration was related to: baseline
      ICH volume (r=0.198, p=0.01); Glasgow Coma Scale (GCS) score 3-8 (p=0.01); GCS
      score 13-15 (p=0.002); midline shift >15 mm (p=0.016); and to subarachnoid
      extension of the blood (p<0.0001). Diabetes mellitus (odds ratio [OR]: 2.93; 95%
      confidence interval [CI]: 1.1-7.76, p=0.031), ICH volume (OR: 1.16; 95% CI: 1.07
      1.27, p<0.0001) and D-dimer concentration (OR: 2.72; 95% CI: 1.08-6.9, p=0.002)
      were associated with 30-day mortality. This study shows that in patients with
      spontaneous ICH, a higher initial D-dimer concentration is associated with higher
      30-day mortality.

PMID- 22377639
TI  - [Is the bacterial vaginosis risk factor of prematurity? Study of a cohort of 1336
      patients in the hospital of Arras].
AB  - BACKGROUND: Among risk factors of prematurity, bacterial vaginosis (BV) could
      play an important role, but few studies took place in our country. AIM: In a
      French population of women booking in a hospital maternity, to search a link
      between prematurity and BV in the first trimester of pregnancy. METHODS: A
      hospital cohort study was carried out between May 2006 and September 1(st), 2009.
      Pregnant women were screening for BV before 13+6 weeks' gestation. BV was
      determined by a Gram-Stained Vaginal score greater or equal to 7. RESULTS: One
      thousand three hundred and thirty-six patients were included in the study among
      whom 203 patients had BV and 1133 patients did not have. The presence of BV was
      significantly associated with preterm delivery (OR: 1.6; 95% IC: 1.1-2.7). But
      this increase concerned only the spontaneous prematurity (ORa: 1.8, 95% IC: 1.0
      3.2) and the statistical association disappeared after taking into account
      maternal tobacco addiction and socio-economic weak level (ORa: 1.6; 95% IC: 0.9
      2.9). At the patient with BV, moreover, the risk of miscarriage before 16SA was
      significantly augmented at the patient with BV (OR: 3.4; 95% IC: 1.1-10.4), but
      this risk disappeared after taking into account tobacco addiction and maternal
      level of studies (ORa: 1.9; 95% IC: 0.5-7.2). CONCLUSION: The presence of BV in
      the first trimester of pregnancy seems to be associated with increased risks of
      preterm delivery and early spontaneous miscarriage. However, this relation seems
      to be partly linked to a level of weaker study and a more frequent tobacco
      addiction among the women with BV.

PMID- 22377640
TI  - [How to classify hormonal contraceptives?].

PMID- 22377641
TI  - Predictors of clinical deterioration during hospitalization following acute
      ischemic stroke.
AB  - BACKGROUND/AIMS: A number of risk factors for early worsening of neurological
      symptoms have been identified. We aimed to evaluate the influence of
      hemorheologic, biochemical, and metabolic factors on neurological deterioration
      during hospitalization following acute ischemic stroke and develop a model of
      neurological deterioration. METHODS: Worsening of stroke was defined as a
      deleterious increase in NIH Stroke Scale (NIHSS) score of >=4 points during
      hospitalization. We performed multivariate logistic regression analysis and
      constructed a prediction model based on chart data of 2,398 patients admitted at
      five medical centers; 203 of the patients had worsening of stroke and 2,186 had
      not. RESULTS: The results of multivariate logistic regression analysis showed
      that hemoglobin (odds ratio: 0.529) and albumin (odds ratio: 0.024) were
      significantly associated with stroke deterioration, as were the modified Rankin
      Scale on emergency department admission (odds ratio: 4.956) and length of
      hospitalization (odds ratio: 1.201). After adjusting for age, gender and NIHSS on
      emergency department admission, only hemoglobin (odds ratio: 0.894, 95%
      confidence interval: 0.814-0.981, p = 0.018) was associated with worsening.
      CONCLUSION: Hemoglobin and albumin were found to be risk factors for persistent
      neurological deterioration during hospitalization following acute ischemic
      stroke, suggesting that blood viscosity may be related to neurological
      deterioration.

PMID- 22377644
TI  - Comparison of cochlear implant relevant anatomy in children versus adults.
AB  - HYPOTHESIS: To test whether there are significant differences in pediatric and
      adult temporal bone anatomy as related to cochlear implant (CI) surgery.
      BACKGROUND: Surgeons rely upon anatomic landmarks including the round window (RW)
      and facial recess (FR) to place CI electrodes within the scala tympani.
      Anecdotally, clinicians report differences in orientation of such structures in
      children versus adults. METHODS: Institutional review board approval was
      obtained. High-resolution computed tomographic scans of 24 pediatric patients (46
      ears) and 20 adult patients (40 ears) were evaluated using software consisting of
      a model-based segmentation algorithm that automatically localizes and segments
      temporal bone anatomy (e.g., facial nerve, chorda tympani, external auditory
      canal [EAC], and cochlea). On these scans, angles pertinent anatomy were manually
      delineated and measured blinded as to the age of the patient. RESULTS: The EAC
      and FR were more parallel to the basal turn (BT) of the cochlea in children
      versus adults ([symbol in text] EAC:BT 20.55 degrees versus 24.28 degrees, p =
      0.003; [symbol in text] FR:BT 5.15 degrees versus 6.88 degrees, p = 0.009). The
      RW was more closely aligned with the FR in children versus adults ([symbol in
      text] FR:RW 30.43 degrees versus 36.67 degrees, p = 0.009). Comparing the lateral
      portion of the EAC (using LatEAC as a marker) to the most medial portion (using
      [symbol in text] TM as a marker), the measured angle was 136.57 degrees in
      children and 172.20 degrees in adults (p < 0.001). CONCLUSION: There are
      significant differences in the temporal bone anatomy of children versus adults
      pertinent to CI electrode insertion.

PMID- 22377645
TI  - Laser Doppler vibrometric assessment of middle ear motion in Thiel-embalmed
      heads.
AB  - HYPOTHESIS: Thiel-embalmed human whole head specimens represent an alternative
      model in middle ear research. BACKGROUND: Research into middle ear mechanics and
      the evaluation of active middle ear implants are generally performed on fresh
      human temporal bone specimens. A drawback of this method is the limited period
      during which the specimen can be used before tissue decay begins. Tissue
      conservation that preserves mechanical properties is desirable. METHODS: Using
      laser Doppler vibrometry, the movement of the tympanic membrane, stapes, and
      round window were measured in 23 ears from 15 human whole head specimens embalmed
      according to Thiel. The ears were acoustically stimulated through the intact
      external auditory canal. The measurement results were compared with data from the
      literature. RESULTS: The results were similar to those measured in living
      subjects and from fresh temporal bones, after excluding measurements with
      nontypical shapes or low amplitudes, that is, 9% for tympanic membrane, 38% for
      stapes, and 67% for round window. The best agreement was found for the tympanic
      membrane (mean difference between 0 and 5.2 dB) and for the stapes measurements
      (mean difference between 0 and 7.4 dB). Larger differences were found for the
      round window measurements (mean difference between 3 and 19 dB). For the
      stimulation levels used, the Thiel specimens behaved linearly in amplitude. The
      results remained reproducible for more than 20 hours in ambient air, and when the
      specimen was put back into Thiel solution, the measurements were stable for up to
      several months between measurements. CONCLUSION: Our results showed that the
      middle ears of Thiel-embalmed human whole head specimens can be used to study
      human middle ear mechanics; however, significant differences in some frequencies,
      particularly at the round window, have to be considered.

PMID- 22377646
TI  - Risk factors associated with vestibular nerve schwannomas.
AB  - INTRODUCTION: Vestibular nerve schwannoma is a benign tumor that originates in
      the sheath of Schwann of the eighth cranial nerve. It is considered one of the
      most common benign intracranial tumors, and its cause is unclear. OBJECTIVE: To
      identify the risk factors associated with vestibular nerve schwannomas. METHODS:
      A hospital-based exploratory case-control study was conducted between 2006 and
      2010 in 2 municipalities in the northeast region of Brazil. We included
      individuals with unilateral vestibular nerve schwannomas confirmed by imaging.
      The controls, selected from the same institutions as the cases, exhibited
      unilateral hearing loss or tinnitus and had undergone investigatory examinations
      similar to those of the cases, but the presence of tumor had been excluded. A
      pretested structured questionnaire, administered by trained interviewers who were
      blind to the condition of the individual being interviewed, was used to obtain
      sociodemographic data and data on potential risk factor exposure. We performed a
      multivariate analysis using unconditional logistic regression. RESULTS: A total
      of 44 patients with vestibular nerve schwannomas and 104 controls participated in
      the study. A history of chicken pox (odds ratio, 6.59; 95% confidence interval,
      2.07-20.9) and the exposure to more than 1 cranial x-ray procedure (odds ratio,
      4.55; 95% confidence interval, 1.10-19.2) were identified as potential risk
      factors. CONCLUSION: This exploratory study brings new hypotheses to be tested
      and thus works toward clarifying the causes and mechanisms involved in the cause
      and development of vestibular nerve schwannoma.

PMID- 22377647
TI  - Galectin-7 as a marker of cholesteatoma residue and its detection during surgery
      by an immunofluorescent method--a preliminary study.
AB  - OBJECTIVES: To visualize the distribution of galectin-7 in middle ear
      cholesteatomas using an immunofluorescent method and to establish whether
      galectin-7 can be used as a marker of cholesteatoma residue at the time of
      operation. METHODS: Middle ear cholesteatomas were obtained at surgery from 30
      patients. Samples were frozen and preserved in a freezer until histological
      study. After serial sectioning with a cryostat, 2 of the specimens were processed
      with primary antibody and Zenon rabbit immunoglobulin G labeling kits. After
      sufficient reaction time, the samples were observed using a confocal laser
      microscope. In the remaining 28 specimens, the cholesteatoma was treated as 1
      block and stained with the same solution. It was then observed using a
      fluorescent stereomicroscope. RESULTS: Confocal microscopic analyses showed that
      galectin-7 was distributed in the cholesteatoma matrix. Because this area
      strongly stained green, it was easily recognized using a confocal laser
      microscope. In the stereomicroscopic study using the 1-block specimen in which
      the cholesteatoma was processed together with the surrounding granulation and
      mucosal tissue, only the matrix and overlying debris was yellow-green in response
      to excitation by light; the surrounding granulation and mucosal tissues did not
      respond in 7 specimens. In the remaining 21 specimens, the whole sample was
      composed of cholesteatoma and responded well to excitation by light. These
      findings suggest that galectin-7 might be a useful marker of cholesteatoma
      residue that can be visualized using this immunofluorescent method. CONCLUSION:
      Because residual cholesteatoma matrix is considered to be one of the main causes
      of cholesteatoma recurrence, staining with galectin-7 at the time of operation
      would be a promising way to facilitate complete removal of the residue.

PMID- 22377648
TI  - Management of CSF leak after vestibular schwannoma surgery.

PMID- 22377649
TI  - Intraoperative monitoring using cochlear microphonics in cochlear implant
      patients with residual hearing.
AB  - OBJECTIVES: To describe a technique for the intraoperative monitoring of residual
      hearing during a cochlear implant (CI) procedure and, thus, to identify the time
      of occurrence and surgical steps leading to hearing loss. STUDY DESIGN:
      Prospective audiologic analysis in a patient series. SETTING: Tertiary referral
      center. SUBJECTS: Patients with residual hearing subjected to cochlear
      implantation. INTERVENTIONS: During cochlear implantation, cochlear microphonics
      (CMs) in response to frequency-specific stimuli were recorded in patients with
      residual hearing. Thresholds were determined before and after opening of the
      cochlea, with a limited portion of the electrode array inserted, and after full
      insertion. RESULTS: Monitoring of the hearing state using CMs was quick,
      reliable, and capable of detecting an intracochlear trauma. In a first series of
      patients, thresholds were preserved in all patients after opening of the cochlea.
      Thresholds were preserved in 5 of 6 patients after limited insertion and half of
      the patients after full insertion of the electrode array. Despite threshold
      preservation until the end of surgery, the residual hearing was lost in patients
      with deep insertions 1 week postoperative. CONCLUSION: Intraoperative monitoring
      of CM thresholds may be valuable for identifying the exact point of time at which
      residual hearing is affected in CI patients. Opening of the cochlea itself seems
      to be unrelated to hearing loss. A significant proportion of patients may have
      hearing loss caused by secondary effects rather than a direct trauma.

PMID- 22377651
TI  - Glomangioma ("true" glomus tumor) presenting as a white middle ear mass behind an
      intact tympanic membrane.

PMID- 22377650
TI  - Dysfunction of the cochlea contributing to hearing loss in acoustic neuromas:  an
      underappreciated entity.
AB  - OBJECTIVE: Hearing loss is a common symptom in patients with cochleovestibular
      schwannoma. Clinical and histologic observations have suggested that the hearing
      loss may be caused by both retrocochlear and cochlear mechanisms. Our goal was to
      perform a detailed assessment of cochlear pathology in patients with vestibular
      schwannoma (VS). STUDY DESIGN: Retrospective analysis of temporal bone
      histopathology. SETTING: Multi-center study. MATERIAL: Temporal bones from 32
      patients with unilateral, sporadic VS within the internal auditory canal. MAIN
      OUTCOME MEASURES: Sections through the cochleae on the VS side and opposite
      (control) ear were evaluated for loss of inner and outer hair cells, atrophy of
      the stria vascularis, loss of cochlear neurons, and presence of endolymphatic
      hydrops and precipitate within the endolymph or perilymph. Observed pathologies
      were correlated to nerve of origin, VS volume, and distance of VS from the
      cochlea. Hearing thresholds also were assessed. RESULTS: VS caused significantly
      more inner and outer hair cell loss, cochlear neuronal loss, precipitate in
      endolymph and perilymph, and decreased pure tone average, when compared with the
      opposite ear. Tumor size, distance from the cochlea, and nerve of origin did not
      correlate with structural changes in the cochlea or the hearing threshold.
      CONCLUSION: There is significant degeneration of cochlear structures in ears with
      VS. Cochlear dysfunction may be an important contributor to the hearing loss
      caused by VS and can explain certain clinically observed phenomena in patients
      with VS.

PMID- 22377652
TI  - End-stage labyrinthitis with extensive erosion of the bony labyrinth.

PMID- 22377653
TI  - Mitral valve dysplasia characterized by isolated cleft of the anterior leaflet
      resulting in fixed left ventricular outflow tract obstruction.
AB  - A 7-month-old, sexually intact male English toy spaniel weighing 4 kg was
      referred for evaluation of a subclinical cardiac murmur. Echocardiography
      disclosed fixed left ventricular outflow tract obstruction that was caused by
      attachment of a cleft anterior mitral valve leaflet to the interventricular
      septum. Neither atrial nor ventricular septal defects were detected. Fixed
      obstruction of the left ventricular outflow tract by a malformed mitral valve is
      rare in human beings and has not been previously reported in the dog.

PMID- 22377655
TI  - Automated landmarking and geometric characterization of the carotid siphon.
AB  - The geometry of the carotid siphon has a large variability between subjects,
      which has prompted its study as a potential geometric risk factor for the onset
      of vascular pathologies on and off the internal carotid artery (ICA). In this
      work, we present a methodology for an objective and extensive geometric
      characterization of carotid siphon parameterized by a set of anatomical
      landmarks. We introduce a complete and automated characterization pipeline.
      Starting from the segmentation of vasculature from angiographic image and its
      centerline extraction, we first identify ICA by characterizing vessel tree
      bifurcations and training a support vector machine classifier to detect ICA
      terminal bifurcation. On ICA centerline curve, we detect anatomical landmarks of
      carotid siphon by modeling it as a sequence of four bends and selecting their
      centers and interfaces between them. Bends are detected from the trajectory of
      the curvature vector expressed in the parallel transport frame of the curve.
      Finally, using the detected landmarks, we characterize the geometry in two
      complementary ways. First, with a set of local and global geometric features,
      known to affect hemodynamics. Second, using large deformation diffeomorphic
      metric curve mapping (LDDMCM) to quantify pairwise shape similarity. We processed
      96 images acquired with 3D rotational angiography. ICA identification had a cross
      validation success rate of 99%. Automated landmarking was validated by computing
      limits of agreement with the reference taken to be the locations of the manually
      placed landmarks averaged across multiple observers. For all but one landmark,
      either the bias was not statistically significant or the variability was within
      50% of the inter-observer one. The subsequently computed values of geometric
      features and LDDMCM were commensurate to the ones obtained with manual
      landmarking. The characterization based on pair-wise LDDMCM proved better in
      classifying the carotid siphon shape classes than the one based on geometric
      features. The proposed characterization provides a rich description of geometry
      and is ready to be applied in the search for geometric risk factors of the
      carotid siphon.

PMID- 22377654
TI  - Temporal effect of Afro-Caribbean race on serum pregnancy-associated plasma
      protein-a at 9-13 weeks' gestation in screening for aneuploidies.
AB  - OBJECTIVE: It was the aim of this study to investigate the pregnancy
      characteristics that influence the measured concentrations of maternal serum-free
      beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma
      protein-A (PAPP-A) at 9(+0)-13(+6) weeks' gestation. METHODS: In singleton
      pregnancies attending for routine care, serum-free beta-hCG and PAPP-A were
      measured at 9(+0)-13(+6) weeks' gestation and fetal nuchal translucency was
      measured at 11(+0)-13(+6) weeks. The population included 27,908 chromosomally
      normal and 104 trisomy 21 pregnancies. Multiple regression analysis was used to
      examine the pregnancy characteristics that have a significant effect on the
      measured concentrations of free beta-hCG and PAPP-A. We also examined the impact
      of incorporating temporal effects on performance of screening for trisomy 21.
      RESULTS: Serum-free beta-hCG and PAPP-A concentrations were significantly
      affected by gestational age, maternal weight, racial origin, parity, preexisting
      diabetes mellitus type 2, smoking and conception by in vitro fertilization. There
      was a significant gestational age-dependent effect of Afro-Caribbean race on PAPP
      A levels (p = 0.0005), with a weekly increase of 4.9% (95% CI 2.1-7.8).
      CONCLUSIONS: Serum-free beta-hCG and PAPP-A concentrations at 9(+0)-13(+6) weeks'
      gestation are affected by several pregnancy characteristics and the effect of
      Afro-Caribbean race on PAPP-A increases with gestational age.

PMID- 22377656
TI  - Brain tissue segmentation in MR images based on a hybrid of MRF and social
      algorithms.
AB  - Effective abnormality detection and diagnosis in Magnetic Resonance Images (MRIs)
      requires a robust segmentation strategy. Since manual segmentation is a time
      consuming task which engages valuable human resources, automatic MRI
      segmentations received an enormous amount of attention. For this goal, various
      techniques have been applied. However, Markov Random Field (MRF) based algorithms
      have produced reasonable results in noisy images compared to other methods. MRF
      seeks a label field which minimizes an energy function. The traditional
      minimization method, simulated annealing (SA), uses Monte Carlo simulation to
      access the minimum solution with heavy computation burden. For this reason, MRFs
      are rarely used in real time processing environments. This paper proposed a novel
      method based on MRF and a hybrid of social algorithms that contain an ant colony
      optimization (ACO) and a Gossiping algorithm which can be used for segmenting
      single and multispectral MRIs in real time environments. Combining ACO with the
      Gossiping algorithm helps find the better path using neighborhood information.
      Therefore, this interaction causes the algorithm to converge to an optimum
      solution faster. Several experiments on phantom and real images were performed.
      Results indicate that the proposed algorithm outperforms the traditional MRF and
      hybrid of MRF-ACO in speed and accuracy.

PMID- 22377657
TI  - Statistical 4D graphs for multi-organ abdominal segmentation from multiphase CT.
AB  - The interpretation of medical images benefits from anatomical and physiological
      priors to optimize computer-aided diagnosis applications. Diagnosis also relies
      on the comprehensive analysis of multiple organs and quantitative measures of
      soft tissue. An automated method optimized for medical image data is presented
      for the simultaneous segmentation of four abdominal organs from 4D CT data using
      graph cuts. Contrast-enhanced CT scans were obtained at two phases: non-contrast
      and portal venous. Intra-patient data were spatially normalized by non-linear
      registration. Then 4D convolution using population training information of
      contrast-enhanced liver, spleen and kidneys was applied to multiphase data to
      initialize the 4D graph and adapt to patient-specific data. CT enhancement
      information and constraints on shape, from Parzen windows, and location, from a
      probabilistic atlas, were input into a new formulation of a 4D graph. Comparative
      results demonstrate the effects of appearance, enhancement, shape and location on
      organ segmentation. All four abdominal organs were segmented robustly and
      accurately with volume overlaps over 93.6% and average surface distances below
      1.1mm.

PMID- 22377658
TI  - Self-protective whole body motion for humanoid robots based on synergy of global
      reaction and local reflex.
AB  - This paper describes a self-protective whole body motor controller to enable life
      long learning of humanoid robots. In order to reduce the damages on robots caused
      by physical interaction such as obstacle collision, we introduce self-protective
      behaviors based on the adaptive coordination of full-body global reactions and
      local limb reflexes. Global reactions aim at adaptive whole-body movements to
      prepare for harmful situations. The system incrementally learns a more effective
      association of the states and global reactions. Local reflexes based on a force
      torque sensing function to reduce the impact load on the limbs independently of
      high-level motor intention. We examined the proposed method with a robot
      simulator in various conditions. We then applied the systems on a real humanoid
      robot.

PMID- 22377659
TI  - Synchrony: a spiking-based mechanism for processing sensory stimuli.
AB  - Synchronous behaviour of neurons is both beneficial and detrimental to the neural
      code. On the one extreme, synchronous firing activity is well known to be a
      symptom of epileptic seizures, whilst on the other synchrony provides a mechanism
      for coordinating brain activity. This paper briefly reviews some current thinking
      with regard to synchrony, and outlines some experiments with LIF neurons that
      harness near-synchronous states for processing biologically-realistic sensory
      stimuli. Inspired by the topology of neurons in the cochlear nucleus, laterally
      connected leaky integrate and fire neurons, operating in near-synchronous states,
      are investigated for their ability to reduce noisy spikes and increase spectral
      contrast of auditory stimuli. Two connectivity parameters, referred to as
      connection length and neighbourhood radius, are introduced to configure lateral
      inhibitory connectivity to generate this neural behaviour. Information-theoretic
      principles are then employed to quantify the information retained by the coding,
      and then this is compared to the information retained by the various output
      topologies.

PMID- 22377660
TI  - Assessing cognitive alignment in different types of dialog by means of a network
      model.
AB  - We present a network model of dialog lexica, called TiTAN (Two-layer Time-Aligned
      Network) series. TiTAN series capture the formation and structure of dialog
      lexica in terms of serialized graph representations. The dynamic update of TiTAN
      series is driven by the dialog-inherent timing of turn-taking. The model provides
      a link between neural, connectionist underpinnings of dialog lexica on the one
      hand and observable symbolic behavior on the other. On the neural side, priming
      and spreading activation are modeled in terms of TiTAN networking. On the
      symbolic side, TiTAN series account for cognitive alignment in terms of the
      structural coupling of the linguistic representations of dialog partners. This
      structural stance allows us to apply TiTAN in machine learning of data of
      dialogical alignment. In previous studies, it has been shown that aligned dialogs
      can be distinguished from non-aligned ones by means of TiTAN -based modeling.
      Now, we simultaneously apply this model to two types of dialog: task-oriented,
      experimentally controlled dialogs on the one hand and more spontaneous, direction
      giving dialogs on the other. We ask whether it is possible to separate aligned
      dialogs from non-aligned ones in a type-crossing way. Starting from a recent
      experiment (Mehler, Lucking, & Menke, 2011a), we show that such a type-crossing
      classification is indeed possible. This hints at a structural fingerprint left by
      alignment in networks of linguistic items that are routinely co-activated during
      conversation.

PMID- 22377661
TI  - Enriched topological learning for cluster detection and visualization.
AB  - The exponential growth of data generates terabytes of very large databases. The
      growing number of data dimensions and data objects presents tremendous challenges
      for effective data analysis and data exploration methods and tools. Thus, it
      becomes crucial to have methods able to construct a condensed description of the
      properties and structure of data, as well as visualization tools capable of
      representing the data structure from these condensed descriptions. The purpose of
      our work described in this paper is to develop a method of describing data from
      enriched and segmented prototypes using a topological clustering algorithm. We
      then introduce a visualization tool that can enhance the structure within and
      between groups in data. We show, using some artificial and real databases, the
      relevance of the proposed approach.

PMID- 22377662
TI  - Cerebrovascular lesions in patients with frontotemporal lobar degeneration: a
      neuropathological study.
AB  - BACKGROUND: Cerebrovascular lesions are frequently observed in Alzheimer brains.
      Not all of them are due to cerebral amyloid angiopathy. Some of them are related
      to the severity of the degenerative process itself, implying additional vascular
      factors in the pathogenesis of Alzheimer's dementia. The aim of the study was to
      investigate the impact of cerebrovascular pathology on brains with frontotemporal
      lobar degeneration (FTLD). PATIENTS AND METHODS: Twenty-two brains with autopsy
      proven FTLD were compared to 15 brains of age-matched patients without evident
      cognitive decline, who died from an illness not related to a brain disease. The
      prevalence and the severity of small ischaemic and haemorrhagic lesions were
      determined. Vascular risk factors and the use of antithrombotic agents were also
      recorded. RESULTS: The patients with FTLD were heterogeneous concerning age of
      onset, disease duration, clinical presentation, genetic background and
      neuropathological typing. Cerebrovascular risk factors and lesions were overall
      rare in FTLD brains without differences in their prevalence and severity compared
      to the controls. Only white matter changes were more prevalent in the FTLD group
      (p = 0.04) and showed a trend to greater severity (p = 0.08). CONCLUSIONS:
      Cerebrovascular pathology is not contributing to the evolution of the disease
      process of patients with FTLD. The isolated prevalence of white matter changes
      should not be considered as a vascular indicator.

PMID- 22377664
TI  - A prospective "oversizing" strategy of the Edwards SAPIEN bioprosthesis: results
      and impact on aortic regurgitation.
AB  - OBJECTIVE: Moderate to severe aortic regurgitation is occurring in 20% to 30% of
      cases after transcatheter aortic valve implantation. METHODS: The purpose of the
      study was to investigate the impact of a prospective policy of "oversizing" the
      Edwards SAPIEN bioprosthesis (Edwards Lifesciences LLC, Irvine, Calif) relative
      to the diameter of the aortic annulus on the rate and severity of aortic
      regurgitation in 28 consecutive patients initially considered eligible for
      transcatheter aortic valve implantation on the basis of angiography, multislice
      computed tomography, and transthoracic echocardiography. This policy included the
      systematic use of transesophageal echocardiography to exclude borderline patients
      and the modification of the procedure to use the larger device possible. The
      results were studied on an individual patient basis. RESULTS: Because 6 of 28
      patients (21%) had an annulus diameter greater than 24 mm by transesophageal
      echocardiography, 22 patients underwent implantation of the Edwards SAPIEN
      prosthesis. In 6 of 22 patients, the procedure was adapted to follow our
      "oversizing" policy. As a result, the "prosthesis/annulus cover index" was 12.4%
      +/- 4.3%. The procedure was successful in 21 of 22 patients (95%), and 18
      patients were available for echocardiography at 1 month. Although a moderate to
      severe aortic regurgitation was observed pretreatment in 4 of 18 patients (22%),
      it was no longer the case at 1 month (0/18, 0%; P = .03). The improvement was
      secondary to a disappearance of the aortic regurgitation in all 7 patients with a
      significant aortic regurgitation at pretreatment, whereas the new aortic
      regurgitations appearing in 5 of the 11 patients with no aortic regurgitation at
      pretreatment were only mild aortic regurgitations. CONCLUSIONS: In patients with
      a successful implantation of an Edwards SAPIEN valve, a simple "oversizing"
      policy based on a systematic use of transesophageal echocardiography and
      modification of the procedure may prevent the occurrence of moderate and severe
      aortic regurgitations.

PMID- 22377665
TI  - Quantitative assessment of right ventricular function in pectus excavatum.

PMID- 22377670
TI  - Impact of stereochemistry on the biological activity of novel oleandomycin
      derivatives.
AB  - A set of 8-methylene-, 8-methyl-, and 8-methyl-9-dihydro-oleandomycin derivatives
      having different combinations of stereochemistries at positions C-8 and/or C-9
      have been prepared in a chemoselective and stereoselective manner and tested in
      vitro for antibacterial activity and inhibition of IL-6 production.
      Configurations of the stereocenters at C-8 and C-9 were determined using 2D NMR
      techniques. We have shown that change of stereochemistry at these positions can
      exert a major influence on antibacterial activity as well as IL-6 inhibition,
      providing novel macrolide derivatives with diminished antibacterial and potent
      anti-inflammatory activity. In addition, the anti-inflammatory activity observed
      in vitro was confirmed in an in vivo model of lipopolysaccharide-induced
      inflammation.

PMID- 22377671
TI  - 2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of
      phenoxodiol, isophenoxodiol, equol and analogues: vasorelaxant properties,
      estrogen receptor binding and Rho/RhoA kinase pathway inhibition.
AB  - Isoflavone consumption correlates with reduced rates of cardiovascular disease.
      Epidemiological studies and clinical data provide evidence that isoflavone
      metabolites, such as the isoflavan equol, contribute to these beneficial effects.
      In this study we developed a new route to isoflavans and isoflavenes via 2
      morpholinoisoflavenes derived from a condensation reaction of
      phenylacetaldehydes, salicylaldehydes and morpholine. We report the synthesis of
      the isoflavans equol and deoxygenated analogues, and the isoflavenes 7,4'
      dihydroxyisoflav-3-ene (phenoxodiol, haganin E) and 7,4'-dihydroxyisoflav-2-ene
      (isophenoxodiol). Vascular pharmacology studies reveal that all oxygenated
      isoflavans and isoflavenes can attenuate phenylephrine-induced vasoconstriction,
      which was unaffected by the estrogen receptor antagonist ICI 182,780.
      Furthermore, the compounds inhibited U46619 (a thromboxane A(2) analogue) induced
      vasoconstriction in endothelium-denuded rat aortae, and reduced the formation of
      GTP RhoA, with the effects being greatest for equol and phenoxodiol. Ligand
      displacement studies of rat uterine cytosol estrogen receptor revealed the
      compounds to be generally weak binders. These data are consistent with the
      vasorelaxation activity of equol and phenoxodiol deriving at least in part by
      inhibition of the RhoA/Rho-kinase pathway, and along with the limited estrogen
      receptor affinity supports a role for equol and phenoxodiol as useful agents for
      maintaining cardiovascular function with limited estrogenic effects.

PMID- 22377672
TI  - Tea catechins and flavonoids from the leaves of Camellia sinensis inhibit yeast
      alcohol dehydrogenase.
AB  - Four new quercetin acylglycosides, designated camelliquercetisides A-D, quercetin
      3-O-[alpha-L-arabinopyranosyl(1->3)][2-O"-(E)-p-coumaroyl][beta-D
      glucopyranosyl(1->3)-alpha-L-rhamnopyranosyl(1->6)]-beta-D-glucoside (17),
      quercetin 3-O-[2-O"-(E)-p-coumaroyl][beta-D-glucopyranosyl(1->3)-alpha-L
      rhamnopyranosyl(1->6)]-beta-D-glucoside (18), quercetin 3-O-[alpha-L
      arabinopyranosyl(1->3)][2-O"-(E)-p-coumaroyl][alpha-L-rhamnopyranosyl(1->6)]-beta
      d-glucoside (19), and quercetin 3-O-[2-O"-(E)-p-coumaroyl][alpha-L
      rhamnopyranosyl(1->6)]-beta-D-glucoside (20), together with caffeine and known
      catechins, and flavonoids (1-16) were isolated from the leaves of Camellia
      sinensis. Their structures were determined by spectroscopic (1D and 2D NMR, IR,
      and HR-TOF-MS) and chemical methods. The catechins and flavonoidal glycosides
      exhibited yeast alcohol dehydrogenase (ADH) inhibitory activities in the range of
      IC(50) 8.0-70.3MUM, and radical scavenging activities in the range of IC(50) 1.5
      43.8 MUM, measured by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

PMID- 22377673
TI  - Proteasome inhibitors for cancer therapy.
AB  - Proteasome, a large multicatalytic proteinase complex that plays an important
      role in processing of proteins, has been shown to possess multiple catalytic
      activities. Among its various activities, the 'chymotrypsin-like' activity of
      proteasome has emerged as the focus of drug discovery efforts in cancer therapy.
      Herein we report chiral boronate derived novel, potent, selective and cell
      permeable peptidomimetic inhibitors 6 and 7 that displayed activity against
      various rodent and human tumor cell lines (in vitro).

PMID- 22377674
TI  - Novel coumarins and 2-thioxo-coumarins as inhibitors of the tumor-associated
      carbonic anhydrases IX and XII.
AB  - A series of coumarins incorporating tert-butyl-dimethylsilyloxy- or allyoxy-
      moieties in positions 4-, 6 or 7 of the heterocyclic ring have been synthesized
      and then converted to the corresponding 2-thioxo-coumarins. Other derivatives
      incorporating hydroxyethyloxy-, tosylethoxy- and 2-fluroethyloxy- moieties in
      position 7 of the coumarin ring were synthesized together with derivatives of 4
      methyl-7-amino coumarin incorporating acetamido, 3,5-dimethylphenylureido- and
      tert-butyloxycarbonylamido functionalities. All these compounds were assayed as
      inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human
      (h) cytosolic isoforms hCA I and II were weakly inhibited (hCA I) or not
      inhibited at all (hCA II) by these (thioxo)coumarins whereas the tumor-associated
      transmembrane isoforms hCA IX and XII were inhibited with efficiencies from the
      submicromolar to the low micromolar range by many of these derivatives. The
      structure-activity relationship for these classes of less investigated CA
      inhibitors are delineated, with the potential of using them as leads to obtain
      isoform-selective inhibitors with excellent affinity for CA IX and XII (validated
      antitumor targets) which do not significantly inhibit the cytosolic offtarget
      isoforms hCA I and II.

PMID- 22377675
TI  - Indeno[1,2-b]indole derivatives as a novel class of potent human protein kinase
      CK2 inhibitors.
AB  - Herein we describe the synthesis and properties of indeno[1,2-b]indole
      derivatives as a novel class of potent inhibitors of the human protein kinase
      CK2. A set of 19 compounds was obtained using a convenient and straightforward
      synthesis protocol. The compounds were tested for inhibition of human protein
      kinase CK2, which was recombinantly expressed in Escherichia coli. New inhibitors
      with IC(50) in the micro- and sub-micromolar range were identified. Compound 4b
      (5-isopropyl-7,8-dihydroindeno[1,2-b]indole-9,10(5H,6H)-dione) inhibited human
      CK2 with an IC(50) of 0.11 MUM and did not significantly inhibit 22 other human
      protein kinases, suggesting selectivity towards CK2. ATP-competitive inhibition
      by compound 4b was shown and a K(i) of 0.06 MUM was determined. Our findings
      indicate that indeno[1,2-b]indoles are a promising starting point for further
      development and optimization of human protein kinase CK2 inhibitors.

PMID- 22377677
TI  - Disappearance of association in diabetic patients on hemodialysis between anemia
      and mortality risk: the Japan dialysis outcomes and practice pattern study.
AB  - We previously demonstrated that anemia was not associated with mortality in
      hemodialysis patients with cardiovascular disease (CVD). Since diabetes mellitus
      (DM) accelerates CVD, the influence of DM on the relationship between anemia and
      mortality was examined using the data obtained from 1,385 DM patients and 2,583
      non-DM hemodialysis patients recruited into the Dialysis Outcomes Practice
      Pattern Study in Japan (J-DOPPS). When all patients were stratified into four
      groups on their hematocrit levels, mortality rate was significantly and steadily
      lower in the subgroups with the higher levels of hematocrit by the Kaplan-Meier
      method (p = 0.0003 by log-rank test). When DM and non-DM patients were analyzed
      separately, a significant association of lower hematocrit levels with higher
      mortality disappeared in DM patients (p = 0.6280), in contrast with its retention
      in non-DM counterparts (p < 0.0001). Multivariable-adjusted Cox proportional
      hazards models demonstrated a significant association between hematocrit with all
      cause mortality in non-DM patients after adjustment for age, gender, BMI,
      hemodialysis duration, SBP, DBP, albumin, total cholesterol, calcium, phosphorus,
      and intact PTH (p = 0.046), whereas this association disappeared in DM patients
      in the same model (p = 0.583). In conclusion, these results suggested that the
      association between anemia and higher mortality disappeared in DM hemodialysis
      patients, in contrast with non-DM counterparts.

PMID- 22377678
TI  - Successful eradication of Scytalidium dimidiatum-induced ungual and cutaneous
      infection with voriconazole.
AB  - We report the successful treatment of extensive cutaneous infection and
      onychomycosis caused by Scytalidium dimidiatum in a 30-year old Nigerian woman.

PMID- 22377676
TI  - Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected
      cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope
      glycoprotein.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is
      etiologically associated with three neoplastic syndromes: Kaposi sarcoma and the
      uncommon HIV-associated B-cell lymphoproliferative disorders primary effusion
      lymphoma and multicentric Castleman disease. The incidence of the latter B-cell
      pathology has been increasing in spite of antiretroviral therapy; its association
      with lytic virus replication has prompted interest in therapeutic strategies
      aimed at this phase of the virus life cycle. We designed and expressed a
      recombinant immunotoxin (2014-PE38) targeting the gpK8.1A viral glycoprotein
      expressed on the surface of the virion and infected cells. We show that this
      immunotoxin selectively kills KSHV-infected cells in dose-dependent fashion,
      resulting in major reductions of infectious virus release. The immunotoxin and
      ganciclovir, an inhibitor of viral DNA replication, showed marked reciprocal
      potentiation of antiviral activities. These results suggest that the immunotoxin,
      alone or in combination, may represent a new approach to treat diseases
      associated with KSHV lytic replication. 

PMID- 22377680
TI  - Comparative international analysis of radiofrequency exposure surveys of mobile
      communication radio base stations.
AB  - This paper presents analyses of data from surveys of radio base stations in 23
      countries across five continents from the year 2000 onward and includes over
      173,000 individual data points. The research compared the results of the national
      surveys, investigated chronological trends and compared exposures by technology.
      The key findings from this data are that irrespective of country, the year and
      cellular technology, exposures to radio signals at ground level were only a small
      fraction of the relevant human exposure standards. Importantly, there has been no
      significant increase in exposure levels since the widespread introduction of 3G
      mobile services, which should be reassuring for policy makers and negate the need
      for post-installation measurements at ground level for compliance purposes. There
      may be areas close to antennas where compliance levels could be exceeded. Future
      potential work includes extending the study to additional countries, development
      of cumulative exposure distributions and investigating the possibility of linking
      exposure measurements to population statistics to assess the distribution of
      exposure levels relative to population percentiles.

PMID- 22377679
TI  - Hyperbranched polymeric N-oxide: a novel kind of metal-free photocatalyst.
AB  - A N-O bond is introduced into hyperbranched polyimide photocatalysts for the
      first time to change their polarity and modulate electronic structure. Both of
      the changes help improve the photocatalytic ability of the polyimide. This
      strategy shows great prospect for synthesizing effective organic photocatalysts.

PMID- 22377681
TI  - Levels and predictors of airborne and internal exposure to manganese and iron
      among welders.
AB  - We investigated airborne and internal exposure to manganese (Mn) and iron (Fe)
      among welders. Personal sampling of welding fumes was carried out in 241 welders
      during a shift. Metals were determined by inductively coupled plasma mass
      spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption
      spectrometry. Determinants of exposure levels were estimated with multiple
      regression models. Respirable Mn was measured with a median of 62 (inter-quartile
      range (IQR) 8.4-320) MUg/m(3) and correlated with Fe (r=0.92, 95% CI 0.90-0.94).
      Inhalable Mn was measured with similar concentrations (IQR 10-340 MUg/m(3)).
      About 70% of the variance of Mn and Fe could be explained, mainly by the welding
      process. Ventilation decreased exposure to Fe and Mn significantly. Median
      concentrations of MnB and serum ferritin (SF) were 10.30 MUg/l (IQR 8.33-13.15
      MUg/l) and 131 MUg/l (IQR 76-240 MUg/l), respectively. Few welders were presented
      with low iron stores, and MnB and SF were not correlated (r=0.07, 95% CI -0.05 to
      0.20). Regression models revealed a significant association of the parent metal
      with MnB and SF, but a low fraction of variance was explained by exposure-related
      factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced
      MnB and SF, respectively, in welders. This indicates an effect on the biological
      regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF
      were not, likely due to higher iron stores among welders.

PMID- 22377683
TI  - Adverse effects of pesticides on biochemical and haematological parameters in
      Tunisian agricultural workers.
AB  - Biomonitoring of effects in agricultural workers is necessary to assess the
      individual risk of handling pesticides. In this study, biochemical and
      haematological parameters were measured to evaluate the effects of exposure to
      these compounds in agricultural workers. The study was carried out in 110 workers
      and 97 control subjects. Several haematological and biochemical parameters were
      analysed. Assessment of haematological parameters revealed that the mean cell
      volume and haematocrit levels were significantly lower in workers than in
      controls (P=0.002 and 0.013, respectively), while mean corpuscular haemoglobin
      concentrations were higher in workers (P<0.001). There was also a significant
      inhibition of butyrylcholinesterase activity in workers compared with that in
      controls (P<0.001). Assessment of biochemical parameters further showed
      significantly higher activities of transferases, lactate dehydrogenase (P<0.001),
      alkaline phosphatase (ALP) (P=0.006) and creatine kinase (CK) (P<0.015), as well
      as higher levels of proteins (P<0.001), creatinine (P=0.001) and urea (P=0.001)
      in workers compared with controls, along with significantly higher uric acid
      levels (P=0.012). Furthermore, the number of years exposed to pesticides
      predicted higher activities of alanine aminotransferase, CK, ALP, as well as uric
      acid levels. Overall, chronic exposure to pesticides appeared to affect several
      biochemical parameters. These biomarkers seem to be indicative of adverse effects
      of pesticides in agricultural workers, confirming their use for routine
      monitoring of effects.

PMID- 22377682
TI  - Domestic airborne black carbon and exhaled nitric oxide in children in NYC.
AB  - Differential exposure to combustion by-products and allergens may partially
      explain the marked disparity in asthma prevalence (3-18%) among New York City
      neighborhoods. Subclinical changes in airway inflammation can be measured by
      fractional exhaled nitric oxide (FeNO). FeNO could be used to test independent
      effects of these environmental exposures on airway inflammation. Seven- and eight
      year-old children from neighborhoods with lower (range 3-9%, n=119) and higher
      (range 11-18%, n=121) asthma prevalence participated in an asthma case-control
      study. During home visits, FeNO was measured, and samples of bed dust (allergens)
      and air (black carbon; BC) were collected. Neighborhood built-environment
      characteristics were assessed for the 500 m surrounding participants' homes.
      Airborne BC concentrations in homes correlated with neighborhood asthma
      prevalence (P<0.001) and neighborhood densities of truck routes (P<0.001) and
      buildings burning residual oil (P<0.001). FeNO concentrations were higher among
      asthmatics with than in those without frequent wheeze (>=4 times/year) (P=0.002).
      FeNO concentrations correlated with domestic BC among children without seroatopy
      (P=0.012) and with dust mite allergen among children with seroatopy (P=0.020).
      The association between airborne BC in homes and both neighborhood asthma
      prevalence and FeNO suggest that further public health interventions on truck
      emissions standards and residual oil use are warranted.

PMID- 22377684
TI  - Personal exposure monitoring wearing protocol compliance: an initial assessment
      of quantitative measurement.
AB  - Personal exposure sampling provides the most accurate and representative
      assessment of exposure to a pollutant, but only if measures are implemented to
      minimize exposure misclassification and reduce confounders that may cause
      misinterpretation of the collected data. Poor compliance with personal sampler
      wearing protocols can create positive or negative biases in the reported exposure
      concentrations, depending on proximity of the participant or the personal sampler
      to the pollutant source when the monitor was not worn as instructed. This paper
      presents an initial quantitative examination of personal exposure monitor wearing
      protocol compliance during a longitudinal particulate matter personal exposure
      monitoring study of senior citizens of compromise health in North Carolina.
      Wearing compliance varied between participants because of gender or employment
      status, but not longitudinally or between cohorts. A minimum waking wearing
      compliance threshold, 0.4 for this study of senior citizens, is suggested to
      define when personal exposure measurements are representative of a participant's
      exposure. The ability to define a minimum threshold indicates data weighting
      techniques may be used to estimate a participant's exposure assuming perfect
      protocol compliance.

PMID- 22377686
TI  - First-principles study on the reconstruction induced by the adsorption of C60 on
      Pt(111).
AB  - The adsorption of C60 on a Pt(111) surface and the origins of the ?13 * ?13R13.9
      degrees  or 2?3 * 2?3R30 degrees  reconstruction of the C60/Pt(111) system have
      been investigated by means of first-principles calculations. In agreement with
      the experimental observations, our calculations reveal that the C60 molecule
      binds covalently on the Pt(111) surface. The C60 molecule adsorbs on the Pt(111)
      surface with the center of a hexagonal ring located on top of a surface Pt atom.
      The surface Pt atom can be removed easily, forming a Pt vacancy upon the
      adsorption of C60 molecule. Our calculation results show that the strong covalent
      bonds between C60 and the Pt(111) surface and the formation of adatom-vacancy
      pairs in the C60/Pt(111) system may be the main driving forces promoting the
      substrate reconstructing pattern observed in experiments.

PMID- 22377688
TI  - Triterpene saponins from Antonia ovata leaves.
AB  - Six pentacyclic triterpenoid saponins, named antoniosides E-J along with two
      known alkaloids, were isolated from the leaves of Antonia ovata. Their structures
      were determined by the extensive use of 1D and 2D-NMR experiments along with
      HRESIMS analysis and acid hydrolysis. All isolated saponins contained the same
      pentasaccharide chain: 3-O-[beta-D-glucopyranosyl-(1->2)]-[beta-D-glucopyranosyl
      (1->4)]-[beta-D-glucopyranosyl-(1->3)-alpha-L-arabinopyranosyl(1->6)]-beta-D
      glucopyranoside, linked at C-3 of esterified derivatives of polyhydroxyoleanene
      triterpenoids (theasapogenol A and 15alpha-hydroxy-theasapogenol A). Isolated
      compounds were evaluated for their cytotoxic activity against KB cell line by a
      WST-1 assay, and the IC(50) values ranged from 3.3 to 5.3 MUM.

PMID- 22377689
TI  - Formation of biphenyl and dibenzofuran phytoalexins in the transition zones of
      fire blight-infected stems of Malus domestica cv. 'Holsteiner Cox' and Pyrus
      communis cv. 'Conference'.
AB  - In the rosaceous subtribe Pyrinae (formerly subfamily Maloideae), pathogen attack
      leads to formation of biphenyls and dibenzofurans. Accumulation of these
      phytoalexins was studied in greenhouse-grown grafted shoots of Malus domestica
      cv. 'Holsteiner Cox' and Pyrus communis cv. 'Conference' after inoculation with
      the fire blight bacterium, Erwinia amylovora. No phytoalexins were found in
      leaves. However, both classes of defence compounds were detected in the
      transition zone of stems. The flanking stem segments above and below this zone,
      which were necrotic and healthy, respectively, were devoid of detectable
      phytoalexins. The transition zone of apple stems contained the biphenyls 3
      hydroxy-5-methoxyaucuparin, aucuparin, noraucuparin and 2'-hydroxyaucuparin and
      the dibenzofurans eriobofuran and noreriobofuran. In pear, aucuparin, 2'
      hydroxyaucuparin, noreriobofuran and in addition 3,4,5-trimethoxybiphenyl were
      detected. The total phytoalexin content in the transition zone of pear was 25
      times lower than that in apple. Leaves and stems of mock-inoculated apple and
      pear shoots lacked phytoalexins. A number of biphenyls and dibenzofurans were
      tested for their in vitro antibacterial activity against some Erwinia amylovora
      strains. The most efficient compound was 3,5-dihydroxybiphenyl (MIC=115 MUg/ml),
      the immediate product of biphenyl synthase which initiates phytoalexin
      biosynthesis.

PMID- 22377690
TI  - Oleanolic acid.
AB  - Oleanolic acid (3beta-hydroxyolean-12-en-28-oic acid) is a pentacyclic
      triterpenoid compound with a widespread occurrence throughout the plant kingdom.
      In nature, the compound exists either as a free acid or as an aglycone precursor
      for triterpenoid saponins, in which it can be linked to one or more sugar chains.
      Oleanolic acid and its derivatives possess several promising pharmacological
      activities, such as hepatoprotective effects, and anti-inflammatory, antioxidant,
      or anticancer activities. With the recent elucidation of its biosynthesis and the
      imminent commercialization of the first oleanolic acid-derived drug, the compound
      promises to remain important for various studies. In this review, the recent
      progress in understanding the oleanolic acid biosynthesis and its pharmacology
      are discussed. Furthermore, the importance and potential application of synthetic
      oleanolic acid derivatives are highlighted, and research perspectives on
      oleanolic acid are given.

PMID- 22377691
TI  - Multimodal CT imaging and recanalizing therapy in acute ischemic stroke:
      retrospective analysis of a one-year single-center experience.
AB  - BACKGROUND: Recanalizing therapy in ischemic stroke is restricted to thrombolysis
      within 3 h. Multimodal imaging of vessel and parenchymal perfusion status may
      allow the extension of this time window. AIM: To retrospectively analyze
      treatment results of any recanalizing therapy in clinical practice. METHODS:
      Patients comprised three groups: 'standard' intravenous thrombolysis within 3 h;
      'off-label' intravenous thrombolysis, and off-label interventional therapy.
      Recanalizing therapy was applied dependent on multimodal CT according to
      standardized pathways. Short-term clinical courses were analyzed. RESULTS: Of 543
      patients (ischemic stroke, TIA), 68 (12.5%) received some type of recanalizing
      therapy. Of these, 47 (mean age 73.4, 24 female, mean symptom onset and hospital
      admission 62 min) received standard and 10 off-label thrombolysis (70.8, 6
      female, 332 min), and 11 interventional therapy, mostly mechanical thrombectomy
      (mean age 62.5, 7 female, 186 min). Mean Delta short-term National Institutes of
      Health Stroke Scale (2-5 days) in these three groups were 3.7 +/- 4.7, 3.9 +/-
      4.4, and 4.1 +/- 5.8, respectively. The short-term clinical benefit was similar
      in the three groups. CONCLUSION: Off-label therapy is considered to have a higher
      risk of complications. However, if multimodal CT imaging of acute ischemic stroke
      is incorporated in everyday clinical decision-making, the rate of effective
      recanalizing procedures may be increased without an apparent negative effect on
      short-term outcome.

PMID- 22377692
TI  - Relating magnitudes: the brain's code for proportions.
AB  - Whereas much is known about how we categorize and reason based on absolute
      quantity, data exploring ratios of quantities, as in proportions and fractions,
      are comparatively sparse. Until recently, it remained elusive whether these two
      representations of number are connected, how proportions are implemented by
      neurons and how language shapes this code. New data derived with complementary
      methods and from different model systems now shed light on the mechanisms of
      magnitude ratio representations. A coding scheme for proportions has emerged that
      is remarkably reminiscent of the representation of absolute number. These novel
      findings suggest a sense for ratios that grants the brain automatic access to
      proportions independently of language and the format of presentation.

PMID- 22377693
TI  - First-trimester screening for neural tube defects using alpha-fetoprotein.
AB  - OBJECTIVE: To assess the potential value of maternal serum alpha-fetoprotein
      (AFP) at 11-13 weeks' gestation in early screening for fetal neural tube defects
      (NTDs). METHODS: Maternal serum AFP at 11-13 weeks' gestation was measured in 32
      cases of fetal NTDs, including 18 cases of acrania and 14 cases of spina bifida,
      and 1,500 unaffected controls. The measured serum AFP was converted into multiple
      of the expected median (MoM) after adjustment for gestational age and maternal
      characteristics and Mann-Whitney test was used to determine the significance of
      difference in the mean MoM of serum AFP in the NTD group to that in the controls.
      RESULTS: The mean AFP MoM in the NTD group (1.76, 95% CI 1.39-2.23) was
      significantly higher than in the controls (p < 0.0001). The mean AFP MoM was not
      significantly different between the cases of acrania and cases of spina bifida
      (1.78 vs. 1.75; p = 0.722). The detection rates of NTD in screening by serum AFP
      were 50.0% (95% CI 31.9-68.1) and 37.5% (95% CI 21.1-56.3) at fixed false
      positive rates of 10 and 5%, respectively. CONCLUSION: Measurement of maternal
      serum AFP at 11-13 weeks' gestation may be useful in screening for fetal NTDs.

PMID- 22377694
TI  - [Is it possible to improve access to kidney transplantation waiting list in
      France?].

PMID- 22377695
TI  - Origin of metastases: subspecies of cancers generated by intrinsic karyotypic
      variations.
AB  - Conventional mutation theories do not explain (1) why the karyotypes of
      metastases are related to those of parental cancers but not to those of
      metastases of other cancers and (2) why cancers metastasize at rates that often
      far exceed those of conventional mutations. To answer these questions, we advance
      here the theory that metastases are autonomous subspecies of cancers, rather than
      mutations. Since cancers are species with intrinsically flexible karyotypes, they
      can generate new subspecies by spontaneous karyotypic rearrangements. This
      phylogenetic theory predicts that metastases are karyotypically related to
      parental cancers but not to others. Testing these predictions on metastases from
      two pancreatic cancers, we found: (1) Metastases had individual karyotypes and
      phenotypes. The karyotypes of metastases were related to, but different from,
      those of parental cancers in 11 out of 37 and 26 out of 49 parental chromosomal
      units. Chromosomal units are defined as intact chromosomes with cancer-specific
      copy numbers and marker chromosomes that are > 50% clonal. (2) Metastases from
      the two different cancers did not share chromosomal units. Testing the view that
      multi-chromosomal rearrangements occur simultaneously in cancers, as opposed to
      sequentially, we found spontaneous non-clonal rearrangements with as many new
      chromosomal units as in authentic metastases. We conclude that metastases are
      individual autonomous species differing from each other and parental cancers in
      species-specific karyotypes and phenotypes. They are generated from parental
      cancers by multiple simultaneous karyotypic rearrangements, much like new
      species. The species-specific individualities of metastases explain why so many
      searches for commonalities have been unsuccessful.

PMID- 22377696
TI  - Finding a needle in the haystack: recognition of DNA damage by collaboration
      between DNA repair proteins able to perform DNA charge transport.

PMID- 22377697
TI  - Morphology of the male reproductive system and spermatozoa in Centris Fabricius,
      1804 (Hymenoptera: Apidae, Centridini).
AB  - The genera Centris and Epicharis constitute the Centridini and are widely
      distributed in the Neotropical region. Centris is also found in the southern
      portion of the Neartic region, although both genera are more abundant in the
      humid tropical regions. To describe the structure of the male reproductive system
      and spermatozoa, light and transmission electron microscopy were used. The male
      reproductive system of Centris sp. is formed by a pair of testes, a pair of
      deferent ducts, a pair of seminal vesicles, a pair of accessory glands and an
      ejaculatory duct connected to the external genitalia, the aedeagus. In this
      species, testes and the pre-vesicular deferens ducts as well as the seminal
      vesicles are encapsulated in a single conjunctive capsule, the scrotal membrane.
      Each testis consists of four testicular follicles, made up of cysts with up to 64
      germinative cells. Histologically, the seminal vesicles are formed by a simple
      cylindrical epithelium, basal membrane and muscular tunic. The spermatozoa of
      Centris analis, C. fuscata, C. tarsata and Centris sp. are morphologically
      similar. They have two easily distinguishable regions: the head and flagellum.
      The head is formed by the two-layer acrosome, the linear nucleus and the
      flagellum, the centriole adjunct, the axoneme of pattern 9+9+2 microtubules, two
      asymmetric mitochondrial derivatives and two accessory bodies. These Centris
      species share various morphological characteristics of the male reproductive
      system and spermatozoa with the other bees previously described, indicating that
      several characteristics are synapomorphic for the family Apidae. Studies on the
      morphology of the male reproductive system and spermatozoa in Hymenoptera have
      demonstrated the diversity of the information provided by these reproductive
      structures, which can be used in taxonomy studies and the phylogeny of this
      important group of insects.

PMID- 22377699
TI  - Effects of oral administration of Butyrivibrio fibrisolvens MDT-1 on the
      development and healing of atopic dermatitis in NC/Nga mice.
AB  - The purpose of this study was to evaluate the effects of oral administration of
      Butyrivibrio fibrisolvens MDT-1 (MDT-1) on mite antigen-induced atopic dermatitis
      (AD) in NC/Nga mice. When administration of the freeze-dried cells of MDT-1 was
      initiated one week before mite-antigen swabbing, the development of AD-like skin
      lesions was alleviated. The cell homogenate and membrane fraction had similar
      effects, showing that cell components are effective. Freeze-dried cells were
      found to be replaceable by the crude lipopolysaccharide extracted from MDT-1.
      Alleviation of AD was concomitant with a decrease in the serum IgE level.
      Determination of cytokines produced by Peyer's patch cells showed that MDT-1
      administration increased IL-12, tended to increase IFN-gamma, and tended to
      decrease IL-10, but did not affect IL-4. When MDT-1 was administered after the
      skin lesions had progressed, the symptoms were ameliorated, suggesting that MDT-1
      has AD-healing effects. MDT-1 was as effective as prednisolone, but different
      from prednisolone in that MDT-1 showed no detectable side effects such as body
      weight loss. We previously reported that MDT-1 administration prevented and
      alleviated colorectal cancer, sarcoma, and enterocolitis in mice. Taken together,
      MDT-1 might be beneficial for maintaining the health of pet animals and humans.

PMID- 22377698
TI  - Kisspeptin restores pulsatile LH secretion in patients with neurokinin B
      signaling deficiencies: physiological, pathophysiological and therapeutic
      implications.
AB  - Pulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive
      function and abnormalities in pulse frequency give rise to reproductive
      dysfunction. Kisspeptin and neurokinin B (NKB), neuropeptides secreted by the
      same neuronal population in the ventral hypothalamus, have emerged recently as
      critical central regulators of GnRH and thus gonadotropin secretion. Patients
      with mutations resulting in loss of signaling by either of these neuroendocrine
      peptides fail to advance through puberty but the mechanisms mediating this remain
      unresolved. We report here that continuous kisspeptin infusion restores
      gonadotropin pulsatility in patients with loss-of-function mutations in NKB
      (TAC3) or its receptor (TAC3R), indicating that kisspeptin on its own is
      sufficient to stimulate pulsatile GnRH secretion. Moreover, our findings suggest
      that NKB action is proximal to kisspeptin in the reproductive neuroendocrine
      cascade regulating GnRH secretion, and may act as an autocrine modulator of
      kisspeptin secretion. The ability of continuous kisspeptin infusion to induce
      pulsatile gonadotropin secretion further indicates that GnRH neurons are able to
      set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin.

PMID- 22377700
TI  - Maternal risk for Down syndrome is modulated by genes involved in folate
      metabolism.
AB  - Studies have shown that the maternal risk for Down syndrome (DS) may be modulated
      by alterations in folate metabolism. The aim of this study was to evaluate the
      influence of 12 genetic polymorphisms involved in folate metabolism on maternal
      risk for DS. In addition, we evaluated the impact of these polymorphisms on serum
      folate and plasma methylmalonic acid (MMA, an indicator of vitamin
      B<formula>_{12}</formula> status) concentrations. The polymorphisms
      transcobalamin II (TCN2) c.776C>G, betaine-homocysteine S-methyltransferase
      (BHMT) c.742A>G, methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) c.677 C>T
      and the MTHFR 677C-1298A-1317T haplotype modulate DS risk. The polymorphisms
      MTHFR c.677C>T and solute carrier family 19 (folate transporter), member 1
      (SLC19A1) c.80 A>G modulate folate concentrations, whereas the 5
      methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) c.66A>G
      polymorphism affects the MMA concentration. These results are consistent with the
      modulation of the maternal risk for DS by these polymorphisms.

PMID- 22377701
TI  - PTPN2 is associated with Crohn's disease and its expression is regulated by NKX2
      3.
AB  - PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2
      genetic variants (rs2542151 and rs2542152) were associated with CD in a familial
      IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not
      ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly
      increased in intestinal tissues (p=0.0493), and nearly significantly increased in
      B cells (p=0.0889) from CD patients, but not significantly altered in UC. cDNA
      microarray results found that PTPN2 was down-regulated by NKX2-3 knockdown in
      human cells. We confirmed this observation by RT-PCR analyses in NKX2-3 knockdown
      in B cells from IBD patients and human intestinal microvascular endothelial cells
      (HIMEC). In addition, we found that mRNA expression of another IBD-associated
      gene, NKX2-3, was increased in intestinal tissues and B cells from CD patients,
      but not significantly increased in UC patients. A positive correlation was
      observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal
      tissues from both CD and UC patients. These results suggest that PTPN2 may have
      an important role in CD pathogenesis and may represent a potential diagnostic and
      therapeutic target for IBD.

PMID- 22377702
TI  - GSTT1 null genotype is a risk factor for diabetic retinopathy in Caucasians with
      type 2 diabetes, whereas GSTM1 null genotype might confer protection against
      retinopathy.
AB  - AIM: Substantial data indicate that oxidative stress is involved in the
      development of diabetic retinopathy (DR). The aim of the present study was to
      investigate whether the genetic polymorphisms: polymorphic deletions of
      glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1
      are associated with DR in Slovenian patients with type 2 diabetes. METHODS: In
      this cross sectional case-control study 604 unrelated Slovene subjects
      (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients with DR
      (cases) and the control group of 320 subjects with type 2 diabetes of more than
      10 years' duration who had no clinical signs of DR. Genotypes were determined by
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP). RESULTS: In our study, the deletion of the GSTM1 was found less frequent
      in cases with DR than in the controls (27.5% versus 44.4%; P < 0.001), whereas
      the deletion of GSTT1 was found significantly more often in cases than in the
      controls (49.3% versus 29.7%; P < 0.001). We did not find statistically
      significant differences in the genotype distribution in GSTP1 (Ile105Val)
      polymorphism between cases and controls (40.5% versus 46.0%). CONCLUSIONS: We may
      conclude that individuals homozygous for the deletion of GSTT1 are at an ~ 2-fold
      greater risk of DR, whereas the GSTM1 deficiency is associated with lower
      frequency of DR in type 2 diabetics.

PMID- 22377703
TI  - Gingival crevicular fluid and serum cystatin c levels in periodontal health and
      disease.
AB  - Cystatin C (CSTC) is an inhibitor of cysteine proteinases and could play a
      protective and regulatory role under inflammatory conditions. The present study
      was designed to assess the concentration of CSTC in gingival crevicular fluid
      (GCF) and serum, to find out their association if any, in periodontal health and
      disease. 30 subjects were selected divided into 3 groups consisting of 10
      subjects in each group based on clinical parameters: periodontally healthy group,
      gingivitis group and chronic periodontitis group, while, chronic periodontitis
      group after 8 weeks of the treatment (scaling and root planing) constituted after
      periodontal therapy group. GCF and serum samples were collected from all subjects
      to estimate the levels of CSTC by ELISA. The mean CSTC concentration in GCF and
      serum was observed to be the highest in periodontitis group and lowest in
      periodontally healthy group with intermediate concentration in gingivitis group
      and after periodontal therapy group. CSTC concentration in GCF and serum
      increased proportionally with the severity of periodontal disease (from health to
      periodontitis group) and decreased after treatment. This suggests that CSTC
      increases with disease progression to prevent further periodontal degeneration
      and decreases after treatment due to bone metabolic homeostasis. Further,
      longitudinal prospective studies involving larger population are needed to
      confirm the findings of present study and to better understand the role of CSTC
      in the pathogenesis of periodontal diseases.

PMID- 22377704
TI  - MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with
      rheumatoid arthritis and osteoporosis.
AB  - MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme
      activity and hyperhomocysteinemia, which has been associated with osteoporosis.
      The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis
      with controversial results. The objective of the present study was to investigate
      the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms
      in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck
      and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients,
      and genotyping for the three polymorphisms was performed via restriction fragment
      length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited
      statistically significant differences in the genotype frequencies of MTHFR C677T
      as well as an association with femoral neck BMD; TT homozygotes had lower BMDs
      than patients with the CT genotype, and both of these groups had lower BMDs than
      patients with the CC genotype. The associations of the MTHFR C677T polymorphism
      with osteoporosis/osteopenia and femoral neck BMD suggest that these
      polymorphisms confer a risk of developing osteoporosis in patients with
      rheumatoid arthritis, a risk that may be reduced with folate and B complex
      supplementation.

PMID- 22377705
TI  - Association of MTHFR polymorphisms and chromosomal abnormalities in leukemia.
AB  - Genetic variation in MTHFR gene might explain the interindividual differences in
      the reduction of DNA repaired and the increase of chromosome breakage and damage.
      Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid
      malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy
      was found in several studies, making the MTHFR gene as a good candidate for
      leukemia etiology. Therefore, in this study, we investigated the common sequence
      variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens
      archived after chromosome analysis. The distribution of the MTHFR polymorphisms
      frequency was compared in leukemic patients with structural chromosome
      abnormality and chromosome aneuploidy, as well as in those with no evidence of
      chromosome abnormalities. We observed a significant decrease in the distribution
      of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities
      including both structural aberration and aneuploidy. The same significance result
      also found in patients with structural aberration when compare with the normal
      karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved
      in chromosome abnormalities of leukemia. However, further investigation on the
      correlation with the specific types of chromosomal aberrations is needed.

PMID- 22377706
TI  - Soluble mesothelin-related peptides levels in patients with malignant
      mesothelioma.
AB  - Soluble mesothelin-related peptides (SMRP) are a potential tumor marker for
      malignant mesothelioma. The aim of this study was to determine the differences in
      SMRP levels in patients with malignant mesothelioma before treatment and in
      various responses to treatment and to investigate whether SMRP level could be
      useful in evaluating tumor response to treatment. The study included patients
      with malignant mesothelioma treated at the Institute of Oncology Ljubljana
      between March 2007 and December 2009. Blood samples were collected before
      treatment and/or in various responses to treatment. SMRP levels were determined
      using ELISA assay based upon a combination of two monoclonal antibodies. Mann
      Whitney test was used to determine the differences in SMRP levels in various
      responses to treatment. Median SMRP was 2.80 nmol/L (range 0.00-34.80) before
      treatment, 0.00 nmol/L (range 0.00-0.00) in complete response, 0.48 nmol/L (range
      0.00-4.40) in partial response, 1.65 nmol/L (range 0.00-20.71) in stable disease
      and 7.15 nmol/L (range 0.44-31.56) in progressive disease. Pre-treatment SMRP
      levels were significantly higher than in stable disease, partial response and
      complete response (p=0.006), as were SMRP levels in progressive disease compared
      to stable disease, partial response and complete response (p< 0.001). Our
      findings suggest that SMRP may be a useful tumor marker for detecting the
      progression of malignant mesothelioma and evaluating tumor response to treatment.

PMID- 22377707
TI  - IGF2R genetic variants, circulating IGF2 concentrations and colon cancer risk in
      African Americans and Whites.
AB  - The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a
      type-1 membrane protein that modulates availability of the potent mitogen, IGF2.
      We evaluated the associations between IGF2R non-synonymous genetic variants
      (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)),
      circulating IGF2 levels, and colon cancer (CC) risk among African American and
      White participants enrolled in the North Carolina Colon Cancer Study (NCCCS).
      Generalized linear models were used to compare circulating levels of IGF2 among
      298 African American and 518 White controls. Logistic regression models were used
      to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the
      association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R
      c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml
      compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not
      apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites
      homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC,
      OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not
      associated with CC risk. Our findings support the hypothesis that being
      homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex
      specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk,
      the mechanism may not involve modulation of circulating IGF2.

PMID- 22377708
TI  - Epidemiology and geographical variation of myasthenia gravis in the province of
      Pavia, Italy.
AB  - BACKGROUND AND AIMS: Previous studies have reported a prevalence estimate of
      myasthenia gravis (MG) from 7.7 to 11.1 per 100,000 inhabitants in Europe.
      Moreover, the study of the geographical distribution of MG should be useful to
      generate specific hypotheses. The aims are to estimate MG prevalence and to
      investigate its geographical variation in a delimited area in Northern Italy.
      METHODS: The primary source of data was the MG database of the Neurological
      Institute of Pavia and all other sources of case collection in and outside the
      province. We adopted a Bayesian approach to analyze MG geographical variation
      within the finest geographical grid. RESULTS: We identified 119 live MG prevalent
      cases resident in the province of Pavia on December 31, 2008. The overall crude
      prevalence was 24 per 100,000 inhabitants. The Bayesian analysis identified a
      small cluster of higher MG prevalence in the northern area of the province.
      CONCLUSIONS: The estimated MG prevalence sets the province of Pavia among the
      high-risk areas. The identification of high/low MG risk areas deserves further
      investigation of genetic and environmental factors possibly related to a major
      risk of the disease in that area.

PMID- 22377709
TI  - Association of genetic polymorphisms in the RET-protooncogene and NRG1 with
      Hirschsprung disease in Thai patients.
AB  - Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric
      nervous system known to be associated with the RET-protooncogene and other
      candidates. Recently, a genome-wide association study has added NRG1, a regulator
      of the development of the enteric ganglia precursors, as a new candidate gene.
      The aim of this study is to validate the association of the RET-protooncogene and
      the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide
      polymorphism (SNP) genotyping and PCR-restriction fragment length polymorphism
      for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the
      NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On
      univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all
      four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene)
      and rs2439305 (NRG1) showed the strongest associations with the disease at P
      values of 8.17E-09 (odds ratio (OR)=6.43, 95% confidence intervals (CI)=3.33
      12.40) and 6.94E-03 (OR=3.28, 95% CI=1.28-8.38), respectively. The RET
      protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG
      genotype) was strongly associated with an increased risk of HSCR with a P-value
      of 1.99E-04 (OR=20.34, 95% CI; 2.54-162.78) when compared with a single SNP of
      the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and
      NRG1 is involved in the risk of HSCR development in the Thai population.
      Moreover, the study also detected a combined effect of SNPs by SNP-SNP
      interaction, which may help in predicting HSCR risk.

PMID- 22377710
TI  - A unique demographic history exists for the MAO-A gene in Polynesians.
AB  - Variation in the human monoamine oxidase A (MAO-A) gene can influence
      neurotransmittor levels and is thought to have a role in many behavioral traits.
      The genetic architecture of MAO-A is known to vary across different geographic
      subgroups. Previous studies have reported evidence for positive selection within
      the MAO-A gene region in seven ethnic groups: Pygmy, Aboriginal Taiwanese,
      Chinese, Japanese, Mexican and Russian. Polynesian populations have not been
      tested and repeated founder effects due to the island-hopping voyages of
      Polynesians across the South Pacific suggest a unique demographic history exists
      at the MAO-A gene, perhaps including selective effects. To explore this, we
      genotyped 13 key single-nucleotide polymorphisms (SNPs) spanning MAO-A gene as
      well as the functional polymorphism (MAO-A-uVNTR) in 47 unrelated Maori
      individuals. A comparison of genetic variation between Maori and non-Maori groups
      found a substantial reduction in genetic diversity at the MAO-A gene locus and an
      increase in the frequency of the most common MAO-A gene variant in the Maori
      group. Results of this study support previous findings and also point toward a 5
      SNP haplotype that may have been influenced by selective effects in the Maori
      population. Full-sequence data for MAO-A in a large cohort are now required to
      conclusively determine whether MAO-A has undergone positive selection in
      Polynesians. Overall, these new data describe a unique demographic history for
      the MAO-A gene in the Maori population and will be helpful for studies wishing to
      investigate MAO-A as a candidate gene for influencing behavioral traits in the
      Polynesians.

PMID- 22377711
TI  - Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and
      aspirin exacerbated respiratory diseases.
AB  - Aspirin-exacerbated respiratory diseases (AERD) are associated with the
      metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high
      affinity ligand receptor for potent anti-inflammatory lipid metabolites:
      lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We
      investigated the relationship between single-nucleotide polymorphisms (SNPs) in
      the FPR2 and AERD. Asthmatics were categorized into AERD <15% decreases in forced
      expiratory volume in one second (FEV(1)), and/or naso-ocular reactions after oral
      aspirin challenge (n=170) and aspirin-tolerant asthma (ATA, n=268). In all, 11
      SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in
      peripheral blood were measured using flow cytometric analysis. We performed RT
      PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic
      regression analysis showed that the minor allele frequency of FPR2 -4209T>G
      (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in
      the ATA group (n=268) (P=0.006, P(corr)=0.04, recessive model). The decline of
      FEV(1) after aspirin challenge was significantly lower in the subjects with GG
      homozygotes of FPR2 -4209T>G than those with the other genotypes (P=0.0002).
      Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly
      higher FPR2 protein expression in CD14-positive monocytes than did those with the
      common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the
      expression of the wild form and the exon 2 deleted variant form of FPR2 gene
      according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G
      may have a protective role against the development of AERD, via increase of FPR2
      protein expression in inflammatory cells.

PMID- 22377712
TI  - Association between type 2 diabetes genetic susceptibility loci and visceral and
      subcutaneous fat area as determined by computed tomography.
AB  - Visceral fat accumulation has an important role in the development of several
      metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New
      genetic loci that contribute to the development of type 2 diabetes have been
      identified by genome-wide association studies. To examine the association of type
      2 diabetes susceptibility loci and visceral fat accumulation, we genotyped 1279
      Japanese subjects (556 men and 723 women), who underwent computed tomography for
      measurements of visceral fat area (VFA) and subcutaneous fat area (SFA) for the
      following single-nucleotide polymorphisms (SNPs): NOTCH2 rs10923931, THADA
      rs7578597, PPARG rs1801282, ADAMTS9 rs4607103, IGF2BP2 rs1470579, VEGFA
      rs9472138, JAZF1 rs864745, CDKN2A/CDKN2B rs564398 and rs10811661, HHEX rs1111875
      and rs5015480, TCF7L2 rs7901695, KCNQ1 rs2237892, KCNJ11 rs5215 and rs5219, EXT2
      rs1113132, rs11037909, and rs3740878, MTNR1B rs10830963, DCD rs1153188,
      TSPAN8/LGR5 rs7961581, and FTO rs8050136 and rs9939609. None of the above SNPs
      were significantly associated with VFA. The FTO rs8050136 and rs9939609 risk
      alleles exhibited significant associations with body mass index (BMI; P=0.00088
      and P=0.0010, respectively) and SFA (P=0.00013 and P=0.00017, respectively). No
      other SNPs were significantly associated with BMI or SFA. Our results suggest
      that two SNPs in the FTO gene are associated with subcutaneous fat accumulation.
      The contributions of other SNPs are inconclusive because of a limitation of the
      sample power.

PMID- 22377713
TI  - A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering
      exonic splicing regulatory elements.
AB  - Netherton syndrome (NS) is a rare, life-threatening ichthyosiform syndrome caused
      by recessive loss-of-function mutations in SPINK5 gene encoding lymphoepithelial
      Kazal-type-related inhibitor (LEKTI), a serine protease inhibitor expressed in
      the most differentiated epidermal layers and crucial for skin barrier function.
      We report the functional characterization of a previously unrecognized synonymous
      variant, c.891C>T (p.Cys297Cys), identified in the SPINK5 exon 11 of an NS
      patient. We demonstrated that the c.891C>T mutation is associated with abnormal
      pre-mRNA splicing and residual LEKTI expression in the patient's keratinocytes.
      Subsequent minigene splicing assays and in silico predictions confirmed the
      direct role of the synonymous mutation in inhibiting exon 11 inclusion by a
      mechanism that involves the activity of exonic regulatory sequences, namely
      splicing enhancer and silencer. However, this deleterious effect was not complete
      and a residual amount of normal mRNA and LEKTI protein could be detected,
      correlating with the relatively mild patient's phenotype. Our study represents
      the first identification of a disease-causing SPINK5 mutation that alters
      splicing without affecting canonical splice sites.

PMID- 22377714
TI  - Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in
      the non-diabetic population in Korea.
AB  - We prospectively examined the association between type 2 diabetes mellitus (T2DM)
      progression and common T2DM-risk gene variants in 870 non-diabetic participants
      in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following
      six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated
      channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit
      associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase
      inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene)
      rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG
      (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data
      and metabolic parameters were obtained at baseline and year 4. Pancreatic beta
      cell function was assessed by the homeostasis model assessment index of beta
      cells (HOMA-beta). After 4 years, 137 subjects developed T2DM (15.7%). A
      significant association was found in the variant of KCNQ1 rs2237892, whereas the
      SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C
      allele carriers of KCNQ1 conferred a significantly increased risk for T2DM
      compared with the T/T genotype, independently of clinical risk factors (odds
      ratio=2.61, 95% confidence intervals=1.02-6.69, P=0.04). Although no differences
      were observed at baseline among the KCNQ1 variants, HOMA-beta levels by year 4
      were significantly lower in the C-allele carriers after controlling for metabolic
      parameters. The genetic variations in KCNQ1 are associated with future
      development of T2DM in Koreans, which might be mediated by differences in insulin
      secretory function.

PMID- 22377715
TI  - Influence of improved FcRn binding on the subcutaneous bioavailability of
      monoclonal antibodies in cynomolgus monkeys.
AB  - Engineering monoclonal antibodies (mAbs) with improved binding to the neonatal Fc
      receptor (FcRn) is a strategy that can extend their in vivo half-life and slow
      their systemic clearance. Published reports have predominantly characterized the
      pharmacokinetics of mAbs after intravenous administration. Recently, studies in
      mice suggest FcRn may also play a role in affecting the subcutaneous
      bioavailability of mAbs. Herein, we examined whether five mAbs engineered with
      the T250Q/M428L Fc mutations that improved their FcRn interactions, and
      subsequently their in vivo pharmacokinetics after intravenous administration, had
      improved subcutaneous bioavailability compared with their wild-type counterparts
      in cynomolgus monkeys. Similar to the intravenous administration findings, the
      pharmacokinetic profiles of our variant mAbs after subcutaneous injection showed
      improved half-life or clearance. In contrast, a clear effect was not observed on
      the subcutaneous bioavailability. We expect that while FcRn may play a role in
      determining mAb subcutaneous bioavailability, multiple biopharmaceutical and
      physiological factors are likely to influence the success of engineering
      strategies aimed at targeting this pathway for improving bioavailability.

PMID- 22377716
TI  - New achievements on biological aspects of copper complexes Casiopeinas(r):
      interaction with DNA and proteins and anti-Trypanosoma cruzi activity.
AB  - The mixed-chelate copper(II) complexes Casiopeinas(r) have been tested in several
      models in vitro and in vivo, showing promising antitumoral results. However,
      their mechanism of action remains to be defined. Trying to get a deeper insight
      into their molecular mode of action, further analyses, including gel
      electrophoresis, atomic force microscopy and circular dichroism were carried out
      to study their interaction with DNA and some cytoskeleton proteins. Our results
      revealed that the interaction of Casiopeinas triggers DNA cleavage by a free
      radical mechanism. The tested complexes showed a differential response to
      reducing and scavenger agents. Differences on target preference were also evident
      using double stranded oligonucleotides as sequence competitors. Surprisingly,
      distamycin A, a minor groove binder, enhanced the Casiopeinas' action on DNA. On
      the other hand, the tested Casiopeinas produce strong changes in protein
      structure of tubulin, integrin and fibronectin. All together these results
      suggest a multiple mode of action for these metal-based drugs. In addition, since
      it has been proposed that antitumor drugs efficiently interacting with DNA could
      also show activity against Trypanosoma cruzi, etiologic agent of Chagas disease,
      we evaluated the activity of these compounds on this protozoan parasite. The
      tested complexes showed in vitro anti-T. cruzi activity similar to the anti
      trypanosomal reference drug Nifurtimox.

PMID- 22377717
TI  - Synthesis, characterization and biological studies of new antimony(III) halide
      complexes with omega-thiocaprolactam.
AB  - Three new antimony(III) halide complexes (SbX(3), X=Cl, Br and I) with the
      heterocyclic thione omega-thiocaprolactam (1-azacycloheptane-2-thione, (Hthcl))
      of formulae {[SbCl(2)(MU(2)-Cl)(Hthcl)(2)](n)} (1), {[(SbBr(2)(MU(2)
      Br)(Hthcl)(2))(2)]} (2) and {[(SbI(2)(MU(2)-I)(Hthcl)(2))(2)]} (3) were
      synthesized from the reaction of antimony(III) halides with omega-thiocaprolactam
      in 1:2 stoichiometry. The complexes were characterized by elemental analysis, FT
      IR spectroscopy, (1)H, (13)C NMR spectroscopy and Thermal Gravimetry-Differential
      Thermal Analysis (TG-DTA). Crystal structures of the ligand omega-thiocaprolactam
      and its complexes 1-3 were determined with single crystal X-ray diffraction
      analysis. Complexes 1-3 and omega-thiocaprolactam were evaluated for their in
      vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast
      adenocarcinoma (MCF-7) tumor cell lines. Antimony complexes 1-3 exhibit strong
      antiproliferative activity against both cell lines tested. The higher such
      activity was found for 3 with IC(50) values of 0.12+/-0.04 MUM (LMS) and 0.76+/
      0.16 MUM (MCF-7) which are 60 and 10 times respectively, stronger than that of
      cisplatin. The influence of these complexes 1-3 and omega-thiocaprolactam upon
      the catalytic peroxidation of linoleic acid to hyperoxolinoleic acid by the
      enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The results
      were shown negligible inhibitory activity of 1-3 against LOX.

PMID- 22377729
TI  - Altered cerebral vasoregulation predicts the outcome of patients with partial
      anterior circulation stroke.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate the correlation
      between cerebral hemodynamic changes and the evolution of neurological deficit
      after stroke. METHODS: We included 65 patients with non-lacunar stroke admitted
      to a rehabilitation hospital within 4 weeks from the event. An evaluation of
      cerebrovascular reactivity to hypercapnia was performed with transcranial Doppler
      ultrasonography using the breath-holding index (BHI). Activities of daily living
      status was measured by the Barthel Index (BI) and impairment of mobility was
      assessed by means of the Rivermead Mobility Index (RMI). Multivariate analyses
      were performed using effectiveness of treatment, evaluated on BI and RMI as
      dependent variables. Independent variables were BHI values, age, sex, length of
      stay, hypertension, smoking habit, presence of aphasia and neglect, poststroke
      depression, and the degree of severity of stroke. RESULTS: The effectiveness on
      BI was associated positively with normal BHI values and with neurological
      severity at admission, measured by the Canadian Neurological Scale. The
      regression coefficients for effectiveness on RMI showed that the most relevant
      predictor was ipsilateral BHI (the slope resulted equal to 5.8), followed by age
      (a 10-year age difference is expected to diminish the effectiveness by about
      4.3%) and by depression (depressed patients have almost 11% less effectiveness
      than non-depressed patients). CONCLUSION: These findings suggest that a
      satisfactory recovery from neurologic deficits requires a preserved
      cerebrovascular reactivity in the lesioned hemisphere despite the presence of an
      anatomic lesion.

PMID- 22377730
TI  - Chemokines and chemokine receptors in susceptibility to HIV-1 infection and
      progression to AIDS.
AB  - A multitude of host genetic factors plays a crucial role in susceptibility to HIV
      1 infection and progression to AIDS, which is highly variable among individuals
      and populations. This review focuses on the chemokine-receptor and chemokine
      genes, which were extensively studied because of their role as HIV co-receptor or
      co-receptor competitor and influences the susceptibility to HIV-1 infection and
      progression to AIDS in HIV-1 infected individuals.

PMID- 22377718
TI  - After the bottleneck: Genome-wide diversification of the Mycobacterium
      tuberculosis complex by mutation, recombination, and natural selection.
AB  - Many of the most virulent bacterial pathogens show low genetic diversity and
      sexual isolation. Accordingly, Mycobacterium tuberculosis, the deadliest human
      pathogen, is thought to be clonal and evolve by genetic drift. Yet, its genome
      shows few of the concomitant signs of genome degradation. We analyzed 24 genomes
      and found an excess of genetic diversity in regions encoding key adaptive
      functions including the type VII secretion system and the ancient horizontally
      transferred virulence-related regions. Four different approaches showed evident
      signs of recombination in M. tuberculosis. Recombination tracts add a high
      density of polymorphisms, and many are thus predicted to arise from outside the
      clade. Some of these tracts match Mycobacterium canettii sequences. Recombination
      introduced an excess of non-synonymous diversity in general and even more in
      genes expected to be under positive or diversifying selection, e.g., cell wall
      component genes. Mutations leading to non-synonymous SNPs are effectively purged
      in MTBC, which shows dominance of purifying selection. MTBC mutation bias toward
      AT nucleotides is not compensated by biased gene conversion, suggesting the
      action of natural selection also on synonymous changes. Together, all of these
      observations point to a strong imprint of recombination and selection in the
      genome affecting both non-synonymous and synonymous positions. Hence, contrary to
      some other pathogens and previous proposals concerning M. tuberculosis, this
      lineage may have come out of its ancestral bottleneck as a very successful
      pathogen that is rapidly diversifying by the action of mutation, recombination,
      and natural selection.

PMID- 22377731
TI  - In-vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation
      by vitamins C and E.
AB  - Various efforts have been made in past in order to predict the underlying
      mechanism of pesticide-induced toxicity using in vitro and animal models,
      however, these predictions may or may not be directly correlated with humans. The
      present study was designed to investigate the carbofuran induced genotoxicity and
      its amelioration by vitamins C and E by treating human peripheral blood
      lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0
      MUM) of this compound. The treatment of PBLs with carbofuran displayed
      significant DNA damage in concentration dependent manner. The carbofuran induced
      genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs
      with equimolar (10 MUM) concentration of each of the vitamins C and E; the
      magnitude of protection by vitamin E being higher than by vitamin C. Also, it was
      found that the level of protection by these vitamins was higher when PBLs were
      treated with lower concentrations of pesticide. The significant DNA damage as
      observed by H<formula>_{2}</formula>O<formula>_{2}</formula>, a positive control
      in the present study, and its amelioration by natural antioxidants (vitamins C
      and E) lend an evidence to suggest that carbofuran would have caused genotoxicity
      via pesticide induced oxidative stress.

PMID- 22377732
TI  - Increased salivary levels of 8-hydroxydeoxyguanosine may be a marker for disease
      activity for periodontitis.
AB  - BACKGROUND: 8-hydroxydeoxyguanosine (8-OHdG) is commonly used as a marker to
      evaluate oxidative DNA damage in disorders including chronic inflammatory
      diseases such as inflammatory periodontal pathologies. In the current study we
      hypothesized that the level of 8-OHdG in saliva increases by the periodontal
      destruction severity determined by clinical parameters as clinical attachment
      level (CAL). MATERIALS AND METHODS: A cross-sectional study was conducted on a
      sum of 60 age gender balanced; chronic periodontitis (CP) (n=20), chronic
      gingivitis (CG) (n=20) and healthy (H) (n=20) individuals. Clinical periodontal
      parameters and salivary 8-OHdG levels were evaluated. RESULTS: The mean 8-OHdG
      level in the saliva of the CP group was significantly higher than H and CG groups
      (p< 0.001). Statistically significant correlation was only observed between the
      salivary levels of 8-OHdG and age (p< 0.05), probing depth (PD) and CAL (p<
      0.001) in CP group. However, when CP patients were classified according to their
      CAL levels (CAL? 3 mm (n=11) and CAL<3 mm (n=9)) statistically significant
      correlation was only observed between the salivary levels of 8-OHdG and CAL ? 3
      mm patients (p< 0.001). CONCLUSION: We suggest that elevated salivary levels of 8
      OHdG may be a marker for disease activity and it may reflect indirectly disease
      severity parameters such as CAL.

PMID- 22377733
TI  - Exon dosage variations in Brazilian patients with Parkinson's disease: analysis
      of SNCA, PARKIN, PINK1 and DJ-1 genes.
AB  - Parkinson's disease is one of the most common neurodegenerative disorders
      associated with aging, reaching ~ 2% of individuals over 65 years. Knowledge
      achieved in the last decade about the genetic basis of Parkinson's disease
      clearly shows that genetic factors play an important role in the etiology of this
      disorder. Exon dosage variations account for a high proportion of Parkinson's
      disease mutations, mainly for PARKIN gene. In the present study, we screened
      genomic rearrangements in SNCA, PARKIN, PINK1 and DJ-1 genes in 102 Brazilian
      Parkinson's disease patients with early onset (age of onset ? 50 years), using
      the multiplex ligation-dependent probe amplification method. Family history was
      reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage
      revealed PARKIN and PINK1 copy number variations, but no dosage alteration was
      found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions
      or duplications in the PARKIN gene and only one patient was found to have a
      deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian
      population, which stresses the importance of including exon dosage analysis in
      Parkinson's disease genetic studies.

PMID- 22377734
TI  - Erythrocyte sialic acid content during aging in humans: correlation with markers
      of oxidative stress.
AB  - Sialic acids are substituted neuraminic acid derivatives which are typically
      found at the outermost end of glycan chains on the membrane in all cell types.
      The role of erythrocyte membrane sialic acids during aging has been established
      however the relationship between sialic acid and oxidative stress is not fully
      understood. The present work was undertaken to analyze the relationship between
      erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid
      hydroperoxide levels and plasma total antioxidant capacity. Results show that
      sialic acid content decreases significantly (P< 0.001) in RBC membrane (r= 
      0.901) and increases in plasma (r=0.860) as a function of age in humans. Lipid
      peroxidation measured in the form of hydroperoxides increases significantly
      (P<0.001) in plasma (r=0.830) and RBC membranes (r=0.875) with age in humans. The
      Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be
      significantly decreased (P< 0.001, r=-0.844). We observe significant correlations
      between decrease of erythrocyte membrane sialic acid and plasma lipid
      hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that
      increase in oxidative stress during aging may influence the sialic acid
      decomposition from membrane thereby altering the membrane configuration affecting
      many enzymatic and transporter activities. Considering the importance of plasma
      sialic acid as a diagnostic parameter, it is important to establish age-dependent
      reference.

PMID- 22377735
TI  - Assessment of sialic acid diversity in cancer- and non-cancer related CA125
      antigen using sialic acid-binding Ig-like lectins (Siglecs).
AB  - This study was aimed at obtaining insight into the diversity of sialic acids in
      cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian
      cancer. Starting from available data suggesting the possible relevance of sialic
      acids for discriminating CA125 antigens of different origin, we have employed a
      new experimental approach based on the use of human sialic acid-binding Ig-like
      lectins, Siglecs, as tools for the investigation of sialylation. Siglec-2,
      belonging to the group of evolutionarily conserved Siglecs, and Siglec-3, -6, -7,
      -9 and -10, which are CD33-like Siglecs, were probed in solid-phase binding
      assays with cancer-related CA125 antigens from pleural fluid of patients with
      ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125)
      and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen.
      All Siglecs used showed detectable binding to pCA125 antigen. Siglec-3, Siglec-7
      and Siglec-2 exhibited moderately stronger binding to pCA125 antigen than the
      others. In contrast to this, Siglec-2 and Siglec-3 preferentially recognized
      pfCA125 with greater total binding than for pCA125, whereas Siglec-9 and Siglec
      10 were highly selective for clCA125. Siglecs promise to be powerful tools for
      discriminating CA125 of different origin and could propagate further research on
      other molecular markers of biomedical and diagnostic importance.

PMID- 22377736
TI  - Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for
      gastric cancer.
AB  - Most cases of gastric cancer (GC) are not diagnosed at early stage which can be
      curable, so it is necessary to identify effective biomarkers for its diagnosis
      and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to
      identify genes that are frequently methylated in gastric cancer cell lines.
      Promoter regions hypermethylation of candidate genes were tested by methylation
      specific polymerase chain reaction (MSP) in serum samples, including GC (n=58),
      gastric precancerous lesions (GPL, n=46), and normal controls (NC, n=30). Eighty
      two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4,
      CHRM2, FAM5C, PRAC and MYLK) were selected as the candidate genes. Three genes
      (CHRM2, FAM5C and MYLK) were further confirmed to show methylation rates
      increased with progression from NC to GPL, then to GC. There was obvious decrease
      in detection of FAM5C and MYLK hypermethylation, but not CHRM2, from preoperative
      to postoperative evaluation (P< 0.001). Combined detection of FAM5C and MYLK
      hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre
      warning (30.4%,14/46) than one single gene detection and also had a high
      specificity of 90%. The combined hypermethylated status of FAM5C and MYLK
      correlated with tumor size (P<0.001), tumor invasion depth (P=0.001) and tumor
      node-metastasis (TNM) stage (P=0.003). Hypermethylated FAM5C and MYLK can be used
      as potential biomarkers for diagnosis and pre-warning of GC.

PMID- 22377737
TI  - Evaluation of reference genes and normalization strategy for quantitative real
      time PCR in human pancreatic carcinoma.
AB  - Histologically verified pairs (n=10) of pancreatic tumors and non-neoplastic
      tissues were used for quantitative real-time PCR and the stability of 24
      reference genes was analyzed with geNorm and NormFinder software. Raw C{q} values
      correlated with the degree of RNA degradation. This correlation was abolished by
      normalization to C{q} of 18S endogenous control gene. Both geNorm and NormFinder
      programs suggested EIF2B1, ELF1, MRPL19, and POP4 as the same most stable genes.
      We have thus identified suitable reference genes for future expression studies in
      pancreatic carcinoma. Normalization method reducing the effects of RNA
      degradation on the quality of results was also developed.

PMID- 22377739
TI  - Thrombosis of the aorta abdominalis in infants--diagnosis and thrombolytic
      therapy.
AB  - Aortic thrombosis is rarely observed in neonates and infants. Underlying
      conditions include the presence of umbilical artery catheters, thrombosed
      aneurysm of the ductus arteriosus, sepsis and different states of inherited
      thrombophilia. Treatment options include anticoagulation, thrombolytic therapy
      and thrombectomy. Due to the lack of large studies, neither diagnosis nor
      treatment of neonatal aortic thrombosis are standardized.From 2008-2010, 1
      neonate and 1 infant were admitted to our hospital with symptomatic aortic
      thrombosis.In both patients, diagnosis was made by Doppler ultrasound. Both
      patients were effectively treated with recombinant tissue type plasminogen
      activator. Diagnosis and treatment of 2 infants with symptomatic aortic
      thrombosis are discussed and the literature is reviewed.Since aortic thrombosis
      is a life-threatening condition, early diagnosis by Doppler ultrasound is
      mandatory to initiate treatment without delay. Thrombolytic therapy is a safe
      measure to treat this condition if administered with caution and if the patient
      has not suffered from serious complications such as mesenteric infarction or
      renal failure prior to begin of therapy.

PMID- 22377740
TI  - Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6
      hour urine samples to detect deficiency.
AB  - Aim of the present study was to test whether six-hour (6 h) urine specimens
      predict the 24-hour (24 h) mineral homeostasis in individual infants born
      preterm. Urinary Calcium (Ca) and Phosphate (P) concentrations were studied in 60
      stable infants; gestational age 34 (25-42) weeks. In 58 infants four 6 h urine
      specimens and in 2 infants all spot urine specimens obtained within 24 h were
      analyzed. In 39 infants born preterm coefficients of variation were 0.42 (SD
      0.26) and 0.41 (SD 0.26) for Ca and P measurements in the four 6 h urine
      specimens obtained within 24 h, respectively, The mineral homeostasis of the
      infants was defined as Ca or P surplus homeostasis if the 24 h urinary
      concentrations were >=1 mmol/l. The sensitivity, specificity, and PPV of a 6 h
      urinary specimen to predict Ca deficiency homeostasis (24 h urinary Ca <1 mmol/l)
      were 0.93 (0.77-0.98; 95%CI), 0.72 (0.43-0.90) and 0.90 (0.74-0.96). The
      sensitivity, specificity and PPV for urinary P were 0.8 (0.38-0.96), 0.97 (0.85
      0.995), and 0.8 (0.38-0.96). In conclusion, in infants born preterm on regular 3
      or 4 h feedings, 6 h urine sampling is sufficiently precise for prediction of Ca
      and P mineral deficiency homeostasis (PPV 0.92 and 0.83). However, measurements
      at regular intervals (twice weekly) are recommended not to miss any infant in
      mineral deficiency homeostasis.

PMID- 22377738
TI  - Rituximab in immunologic glomerular diseases.
AB  - Experimental data suggest that the B-cell antigen CD20 may play a significant
      role in the pathogenesis of many diseases including glomerular diseases. These
      and other findings underpin the central concept of B-cell-depleting therapies
      that target CD20 antigen as treatments for lupus nephritis, idiopathic membranous
      nephropathy, focal segmental glomerulosclerosis, cryglobulinemic
      glomerulonephritis, antibody mediated renal allograft rejection and recurrent
      glomerulonephritis in renal allograft. Use of rituximab as a B-cell depleting
      therapy has been associated with clinical improvement and has emerged as a
      possible adjunct or alternative treatment option in this field of nephrology.

PMID- 22377741
TI  - Impact of minimal residual disease detection prior to autologous stem cell
      transplantation for post-transplant outcome in high risk neuroblastoma.
AB  - Autologous stem cell transplantation (SCT) has become standard therapy in high
      risk stage IV neuroblastoma (NB) patients. Residual NB cells in the bone marrow
      (BM) shortly before SCT may shape the overall survival.Thus, we sought to
      thoroughly investigate minimal residual disease (MRD) in BM prior to SCT using
      conventional and real time RT-PCR for tyrosine hydroxylase (TH) as well as
      morphology. To avoid influence of residual NB cells in the stem cell harvest, 17
      patients transplanted with MRD negative grafts (n=11 CD34-selected and n=6
      unmanipulated) are included in the final analysis, only.35% of these patients are
      alive with a median follow up of 8.6 years. In the BM of 9/17 patients residual
      NB cells could be detected < 40 d before SCT. These patients had a significant
      lower overall survival compared to patients without BM involvement based on
      combined RT-PCR and morphology results (11% vs. 62%, p=0.026) or using RT-PCR,
      only (p=0.01). In contrast morphology on its own did not lead to a significant
      discrimination between both groups.Our results obtained in a small cohort of
      stage IV NB patients suggest that MRD diagnostic in the BM shortly before SCT
      might be a valuable predictive tool for these patients but requires conformation
      in a multicenter study.

PMID- 22377742
TI  - Oral levofloxacin-induced optic neuritis progressing in loss of vision.
AB  - This case report highlights a rare adverse drug reaction caused by levofloxacin,
      resulting in optic neuritis progressing into unilateral loss of vision. A 49-year
      old male patient was diagnosed to suffer from left maxillary and ethmoid
      sinusitis and was only prescribed oral levofloxacin 500 mg tablets once daily for
      5 days. Within a few minutes after taking the first dose of the drug, the patient
      experienced respiratory distress, dizziness, confusion with pain, and loss of
      color vision, followed by almost complete loss of vision in the right eye. The
      left eye was normal. After ophthalmologic examinations and investigations, he was
      diagnosed to suffer from optic neuritis, probably (according to Naranjo adverse
      drug reaction probability scale) induced by levofloxacin.

PMID- 22377743
TI  - Predicting plasma concentration of risperidone associated with dosage change:  a
      population pharmacokinetic study.
AB  - BACKGROUND: Due to high interindividual variability in peripheral pharmacokinetic
      parameters, dosing of antipsychotics relies on clinical trial and error. This
      blind process of upward or downward clinical dose titration carries a risk of
      relapse and adverse effects in the treatment of schizophrenia. Using population
      pharmacokinetic methods, the authors therefore sought to predict plasma
      concentrations of risperidone (RIS) plus 9-hydroxyrisperidone (9-OH-RIS) before a
      dosage change. METHODS: Two plasma samples were collected at 2 separate given
      time points for the measurement of RIS and 9-OH-RIS concentrations from 50
      patients with schizophrenia or schizoaffective disorder maintained on risperidone
      (mean +/- SD age = 56 +/- 15 years; 39 men). After an oral risperidone dose
      adjustment, a third sample was collected. The plasma concentration of the third
      sample was individually predicted in a blinded fashion with the 2 baseline plasma
      concentrations before dose adjustment and clinical and demographic information,
      using the mixed-effects model with NONMEM that was derived from the data of the
      Clinical Antipsychotic Trials in Intervention Effectiveness study. RESULTS: The
      mean (95% confidence interval) prediction errors (in ng/mL) were as low as 0.0 (
      1.3 to 1.4) for RIS and 1.0 (-1.1 to 3.0) for 9-OH-RIS. The observed and
      predicted concentrations of RIS and 9-OH-RIS were highly correlated (r = 0.96, P
      < 0.0001 and r = 0.92, P < 0.0001, respectively). CONCLUSIONS: Antipsychotic
      plasma concentrations can be predicted before risperidone dose adjustment. In
      light of the known relationship between plasma drug concentration, dopamine D2
      receptor occupancy, and clinical effects, our results confirm that individualized
      dosing with the measurement of antipsychotic plasma concentrations has the
      potential for bedside clinical application.

PMID- 22377744
TI  - Comparative monitoring of oral theophylline treatment in blood serum, saliva, and
      nasal mucus.
AB  - BACKGROUND: Theophylline, used in the treatment for various pulmonary
      pathologies, is usually given orally with drug levels measured primarily in blood
      serum and occasionally in saliva. Although theophylline treatment is now not
      commonly used it has been effective to correct smell loss (hyposmia). This is
      important because 21 million people in the United States exhibit hyposmia and
      oral theophylline has corrected hyposmia in about 50% of these patients. This
      result suggests that oral theophylline may result in the drug not only appearing
      in the serum but also in nasal mucus, thereby playing a role in correcting
      hyposmia. No prior report of theophylline in nasal mucus has been made and no
      comparison of levels in nasal mucus, blood serum, or saliva has been previously
      reported. PURPOSE: The aim was to determine, after oral theophylline treatment,
      if it is present in nasal mucus and, if present, to compare the levels with those
      in serum and saliva. METHODS: Oral theophylline was given to 23 hyposmic patients
      at daily doses of 200, 300, 400, 600, and 800 mg for periods of 2-10 months.
      During each period, blood serum, saliva, and nasal mucus were collected and
      theophylline measured in each fluid. RESULTS: Theophylline was found in nasal
      mucus and in saliva and blood serum at each drug dose in each patient to whom it
      was given. The mean level of theophylline in nasal mucus was 74% that of serum;
      mean level in saliva was 67% of serum; mean level in nasal mucus was 111% that in
      saliva. CONCLUSIONS: Theophylline is present in nasal mucus after oral
      administration. Levels in nasal mucus reflect blood and saliva levels in a
      consistent manner and offer a simple convenient noninvasive method to monitor
      theophylline doses of the oral drug.

PMID- 22377745
TI  - Effects of paroxetine on plasma concentrations of aripiprazole and its active
      metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia.
AB  - BACKGROUND: The effects of paroxetine coadministration on plasma concentrations
      of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in
      14 Japanese patients with schizophrenia. METHODS: The patients had been treated
      with aripiprazole (24 mg/d in 5 cases, 12 mg/d in 5 cases, and 6 mg/d in 4 cases)
      for at least 2 weeks. Paroxetine 10 mg/d was coadministered during the first
      week, and the dose was increased to 20 mg/d during the second week. Blood samples
      were taken 3 times, before the start of paroxetine and then 1 and 2 weeks after
      paroxetine coadministration. On the same days, the severity of illness and
      extrapyramidal adverse effects were evaluated by the clinical global impressions
      and the Drug-Induced Extra-Pyramidal Symptoms Scale, respectively. Plasma
      concentrations of aripiprazole and dehydroaripiprazole were measured using liquid
      chromatography with mass spectrometric detection. RESULTS: Plasma concentrations
      of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during
      coadministration of paroxetine 10 and 20 mg/d were significantly (P < 0.05)
      higher (1.5-fold and 1.7-fold; 1.4-fold and 1.5-fold) than those before
      paroxetine coadministration. Those values during coadministration of paroxetine
      20 mg/d were also significantly (P < 0.05) higher (1.1-fold and 1.1-fold) than
      those during coadministration of paroxetine 10 mg/d. Plasma concentrations of
      dehydroaripiprazole were unchanged throughout the study period. The mean clinical
      global impression score was significantly (P < 0.05) higher during the paroxetine
      10 mg/d than that before coadministration, whereas the Drug-Induced Extra
      Pyramidal Symptoms Scale scores remained unchanged during the study. CONCLUSIONS:
      This study suggests that lower doses (10-20 mg/d) of paroxetine coadministration
      increase plasma concentrations of aripiprazole and the sum of aripiprazole and
      dehydroaripiprazole.

PMID- 22377746
TI  - The impact of sulfonylureas on tacrolimus apparent clearance revealed by a
      population pharmacokinetics analysis in Chinese adult liver-transplant patients.
AB  - AIMS: The aims of this study were to determine the population pharmacokinetics of
      tacrolimus in Chinese adult liver-transplant recipients and to identify factors
      that may account for this variability. METHODS: Tacrolimus dose and blood
      concentrations, along with clinical data, were collected retrospectively from 262
      liver-transplant recipients. Data were analyzed using a nonlinear mixed-effects
      modeling method. A 1-compartment model with first-order absorption and
      elimination was selected as the base model. The influence of the following
      parameters were explored: (1) demographic characteristics, (2) biochemical and
      hematological laboratory test results, (3) surgery parameters, and (4) commonly
      used comedications. RESULTS: The typical values (interindividual variability
      percent coefficient of variation) for apparent clearance (CL/F) and apparent
      volume of distribution (V/F) were 20.9 L h (23.8%) and 808 l (70.4%),
      respectively. The residual variability was 33.6%. Finally, the 4 covariates that
      showed a strong correlation with CL/F in this study were daily dose, hematocrit,
      total plasma protein, and the coadministration of sulfonylureas. CL/F was reduced
      significantly with sulfonylureas cotherapy, higher hematocrit levels, and
      elevated total protein. Moreover, CL/F increased nonlinearly with larger daily
      doses of tacrolimus. CONCLUSIONS: Concurrent therapy with sulfonylureas
      influenced tacrolimus CL/F in liver transplantation patients. These results and
      model will help clinicians to optimize tacrolimus regimens in Chinese liver
      transplantation patients.

PMID- 22377747
TI  - Improved sensitivity for methotrexate analysis using enzyme multiplied
      immunoassay technique on the Siemens Viva-E instrument.
AB  - BACKGROUND: The available assay kit for methotrexate (MTX) using the Syva enzyme
      multiplied immunoassay technique (EMIT) reagents on the Siemens Viva-E instrument
      allows for the detection of MTX in serum or plasma to concentrations as low as
      0.3 MUmole/L. Current clinical decision points for MTX therapeutic drug
      monitoring and leucorvorin rescue exist at concentrations below that limit.
      OBJECTIVE: The goal of this study was to lower the limit of MTX quantitation to
      0.05 MUmole/L using the EMIT assay technology. METHODS: EMIT MTX assay parameters
      were modified on the Viva-E instrument to increase the sample volume, alter the
      calibration method, and employ an alternate calibrator set created to achieve
      lower detection. Intraassay and interassay precision was assessed for MTX
      controls. RESULTS: We observed a CV of 9.4% for intraassay precision with a bias
      of <0.01% and a CV of 15.7% for interassay precision with a bias of 22.5% for the
      0.05 MUmole/L control. Precision data for all other controls were <4%. The
      modified EMIT MTX assay and the unmodified approved assay were compared with a
      high sensitivity fluorescence polarization immunoassay method. Linear regression
      of correlation data revealed that both the modified and the commercial EMIT
      assays produced positive bias compared with the high sensitivity fluorescence
      polarization immunoassay method (y-int = 0.03 and 0.08, respectively). However,
      the modified EMIT assay had the best correlation in the low range (0.03-2
      MUmole/L). Additionally, endogenous and chemical interference testing
      demonstrated that the modified assay was not affected to a clinically significant
      extent. CONCLUSIONS: The described modifications have enhanced the sensitivity of
      the Syva EMIT assay for MTX measurements down to 0.05 MUmole/L with acceptable
      precision that can be used in clinical practice for monitoring MTX therapy.

PMID- 22377748
TI  - Optimal storage temperature and matrix before analyzing mycophenolic acid.
AB  - BACKGROUND: The immunosuppressant mycophenolic acid (MPA) is widely used in solid
      organ transplantation and increasingly in hematological conditions and autoimmune
      disease. Concentration monitoring is generally restricted to specialist
      laboratories associated with transplant centers to which samples are referred,
      and delays in transit may occur both from the patient to the local laboratory and
      from there to the specialist laboratory. The instability of the mycophenolate
      glucuronides in plasma is well described, but the data on MPA stability in
      patient samples are limited, particularly in whole blood. This study was designed
      to assess the stability of MPA in patient samples and to establish the correct
      sample type and optimal transport conditions for therapeutic drug monitoring.
      METHODS: Whole-blood samples received in the laboratory for MPA estimation within
      2 hours of phlebotomy were aliquoted, separated, and stored at a range of
      temperatures designed to mimic the range of transit times and conditions seen in
      this laboratory. Ten whole-blood samples were stored for a maximum of 4 weeks at
      4 degrees C, 21 degrees C, or 35 degrees C and plasma at -20 degrees C, 4 degrees
      C, 21 degrees C, and 35 degrees C. MPA concentrations were measured by liquid
      chromatography-tandem mass spectrometry. RESULTS: In whole blood at 35 degrees C,
      there was a significant increase (P = 0.004) in median MPA concentration over
      time, but concentrations decreased in some samples. At 21 degrees C and 4 degrees
      C, there were more modest increases (P = 0.04 and 0.02). In plasma at 35 degrees
      C, there was a significant increase from day 3 to day 28, then a decrease to day
      96 in measured MPA concentration. At 21 degrees C, there was a progressive
      increase in concentration from 7 to 96 days of storage (P < 0.0001). At 4 degrees
      C and -20 degrees C, plasma samples were stable for 28 days after collection, but
      at -20 degrees C, there was a subsequent median increase in concentration of
      15.2% at day 96. CONCLUSIONS: Samples should be separated as soon as practicable
      after collection and stored at -20 degrees C or 4 degrees C before transport to
      the analytical laboratory using subambient temperatures if possible.

PMID- 22377749
TI  - Non-fatal dog bite injuries in the U.S.A., 2005-2009.

PMID- 22377751
TI  - Calcium oxalate monohydrate crystals stimulate monocyte chemoattractant protein-1
      and transforming growth factor beta1 expression in human renal epithelial cells.
AB  - Crystal-cell interactions play a key role in the formation of kidney stones. Few
      studies have referred to the role of monocyte chemoattractant protein-1 (MCP-1)
      and transforming growth factor beta1 (TGFbeta1) in kidney stone formation.
      Recently, a genome-wide analysis of genes related to kidney stone formation and
      eliminiation in mice indicated that MCP-1 and TGFbeta1 are involved in
      nephrolithiasis. In this study, in order to verify whether MCP-1 and TGFbeta1 are
      involved in the process of crystal-cell interactions in vitro, we observed the
      effects of calcium oxalate monohydrate (COM) on MCP-1 and TGFbeta1 expression in
      cultured HK-2 cells. HK-2 cells were treated with different concentrations of
      COM, and a group of untreated cells served as the control. The expression of MCP
      1 and TGFbeta1 was detected by western blot analysis after treatments with
      different COM concentrations (300, 500, 700 and 900 ug/ml) for different times
      (3, 6, 12 and 24 h). We found that the expression of MCP-1 was upregulated by COM
      treatment in a dose-dependent manner, and was increased initially at the first 6
      h of treatment, then slightly decreased over time. Also, COM treatment resulted
      in a dose-dependent increase in TGFbeta1 expression, and the expression levels
      peaked at 12 h. This study demonstrates that COM stimulates the expression of MCP
      1 and TGFbeta1 in renal epithelial cells.

PMID- 22377752
TI  - Smoking is not a risk factor for sporadic amyotrophic lateral sclerosis in an
      Australian population.
AB  - BACKGROUND: Controversy persists as to whether smoking is a risk factor for
      sporadic amyotrophic lateral sclerosis (SALS), the most common form of sporadic
      motor neuron disease (SMND). We therefore undertook a large case-control study of
      smoking and SALS in Australia. METHODS: Cases and controls were recruited
      Australia-wide over a 10-year period. SALS and the other subgroups of SMND were
      categorised on the basis of neurologists' reports. Controls were partners or
      friends of SMND patients or community volunteers. Individuals filled in a
      questionnaire regarding smoking habits. A total of 809 patients with SMND (631
      with SALS) and 779 controls were included in the study. SALS males and females
      were analysed separately. RESULTS: No differences between SALS patients and
      control groups were found with regard to (1) the odds ratios of ever-smokers, ex
      smokers or current smokers compared to never-smokers, (2) the means of numbers of
      cigarettes per day, years of smoking, pack years or age smoking began or (3) the
      proportions of their parents who had ever smoked. The proportion of ever-smokers
      and mean pack years did not differ between the clinical subgroups of SMND or
      between different sites of SALS onset. Partner smoking did not increase the risk
      of SMND. CONCLUSION: This Australian case-control study does not support a link
      between cigarette smoking and any form of SMND.

PMID- 22377750
TI  - Aglycosylated antibodies and antibody fragments produced in a scalable in vitro
      transcription-translation system.
AB  - We describe protein synthesis, folding and assembly of antibody fragments and
      full-length aglycosylated antibodies using an Escherichia coli-based open cell
      free synthesis (OCFS) system. We use DNA template design and high throughput
      screening at microliter scale to rapidly optimize production of single-chain Fv
      (scFv) and Fab antibody fragments that bind to human IL-23 and IL-13alpha1R,
      respectively. In addition we demonstrate production of aglycosylated
      immunoglobulin G (IgG 1) trastuzumab. These antibodies are produced rapidly over
      several hours in batch mode in standard bioreactors with linear scalable yields
      of hundreds of milligrams/L over a 1 million-fold change in scales up to pilot
      scale production. We demonstrate protein expression optimization of translation
      initiation region (TIR) libraries from gene synthesized linear DNA templates,
      optimization of the temporal assembly of a Fab from independent heavy chain and
      light chain plasmids and optimized expression of fully assembled trastuzumab that
      is equivalent to mammalian expressed material in biophysical and affinity based
      assays. These results illustrate how the open nature of the cell-free system can
      be used as a seamless antibody engineering platform from discovery to preclinical
      development of aglycosylated monoclonal antibodies and antibody fragments as
      potential therapeutics.

PMID- 22377753
TI  - The cost-effectiveness of biopharmaceuticals: a look at the evidence.
AB  - Due to the increasing availability and costs of biopharmaceuticals, policymakers
      are questioning whether they provide good value relative to other health
      interventions and many are increasingly relying on cost-utility analyses (CUAs)
      to supplement decision-making. Analyzing data from the Tufts Medical Center Cost
      Effectiveness Analysis Registry, this study critically reviewed the cost-utility
      literature for biopharmaceuticals and compared their value to other health
      interventions. Of 2,383 studies in the registry, biopharmaceutical CUAs comprised
      the sixth largest category of interventions at 11%. Characteristics of
      biopharmaceutical articles were similar to other CUAs; however, they displayed
      slightly better quality. The median cost-effectiveness ratio of
      biopharmaceuticals was less favorable (i.e., higher) than other interventions
      though many seem to provide value for money. A logistic regression showed that
      among biopharmaceuticals the cost-effectiveness of industry-sponsored studies and
      products that treat infectious diseases were significantly more likely to be
      favorable (less than the overall median), while cancer and neurological
      treatments were significantly less likely. 

PMID- 22377754
TI  - Predictive studies of H-atom abstraction reactions by an iron(IV)-oxo corrole
      cation radical oxidant.
AB  - Density functional theory calculations compare the reactivity of iron(IV)-oxo
      porphyrin and corrole cation radical species in H-atom abstraction reactions.

PMID- 22377755
TI  - The upper airway resistance syndrome.
AB  - Obstructive sleep apnea syndrome has been recognized as a major public health
      problem. Both its cardiovascular and metabolic comorbidities and symptoms
      motivate for an accurate diagnosis and appropriate treatment. The main stimulus
      associated with obstructive sleep apnea (OSA) and explaining deleterious
      consequences is intermittent hypoxia. The upper airway resistance syndrome (UARS)
      has been described based on the hypothesis that snoring and repetitive occurrence
      of respiratory effort-related arousals (RERAs) but not oxygen desaturation might
      produce a significant disease with symptoms, altered quality of life and
      cardiovascular morbidity. Diurnal sleepiness remains the main diagnostic
      criteria, which is often confounded with tiredness in women. UARS patients may
      also report insomnia and symptoms that closely resemble those of the functional
      somatic syndromes. Currently, the International Classification of Sleep Disorders
      does not individualize UARS as a specific entity and reports UARS patients as a
      subgroup of OSA. However, RERAs are described as unambiguous abnormal respiratory
      events occurring during sleep and requiring a specific scoring. In this review,
      the authors attempt to describe the specific characteristics of UARS that are
      relevant for both clinicians and researchers.

PMID- 22377756
TI  - Mammary fistula could be included in the follicular occlusion tetrad.

PMID- 22377757
TI  - Fractionated laser resurfacing corrects the inappropriate UVB response in
      geriatric skin.
AB  - Non-melanoma skin cancer is a disease primarily afflicting geriatric patients as
      evidenced by the fact that 80% of all non-melanoma skin cancers are diagnosed in
      patients over the age of 60 years. As such, geriatric skin responds to cancer
      inducing UVB irradiation in a manner that allows the establishment of tumor
      cells. Currently, the only effective treatment for non-melanoma skin cancer is
      the removal of the tumors after they appear, indicating the need for a more cost
      effective prophylactic therapy. Geriatric volunteers were treated with
      fractionated laser resurfacing therapy on either sun-protected (upper buttocks)
      or chronically sun-exposed (dorsal forearm) skin. Fractionated laser resurfacing
      therapy was shown to decrease the occurrence of senescent fibroblasts in
      geriatric dermis, increase the dermal expression of IGF-1, and correct the
      inappropriate UVB response observed in untreated geriatric skin. These responses
      to fractionated laser resurfacing were equal to the effects seen previously using
      the more aggressive wounding following dermabrasion. Furthermore, fractionated
      laser resurfacing was equally effective in both sun-protected and sun-exposed
      skin. The ability of fractionated laser resurfacing treatment to protect against
      the occurrence of UVB-damaged proliferating keratinocytes indicates the potential
      of fractionated laser resurfacing to reduce or prevent aging-associated non
      melanoma skin cancer.

PMID- 22377758
TI  - Cloning a human saliva-derived peptide for preventing KSHV transmission.

PMID- 22377759
TI  - Molecular markers of early-stage mycosis fungoides.
AB  - The lack of a specific marker differentiating early mycosis fungoides (eMF) from
      benign inflammatory dermatitis presents significant difficulties in the
      assessment and management of suspected MF patients, which often leads to delayed
      diagnosis and improper medical approaches. To address this, an investigation was
      carried out to characterize positive identification markers for eMF by comparing
      eMF lesions with healthy skin and benign inflammatory dermatitis, using high
      throughput genomic transcription profiling. A total of 349 genes were
      differentially expressed in eMF lesions compared with normal skin. These genes
      belong to pathways associated with inflammation, immune activation, and apoptosis
      regulation. Most of them (N=330) also demonstrated significant upregulation in
      chronic dermatitis, making them nonideal markers for eMF. Among them, 19 genes
      with specific enrichment in eMF lesions were identified that showed no
      significant upregulation in chronic dermatitis. Two of them, TOX and PDCD1,
      showed high discrimination power between eMF lesions and biopsies from benign
      dermatitis by RNA expression. Furthermore, TOX demonstrated highly specific
      staining of MF cells in eMF skin biopsies in immunohistochemistry and
      immunofluorescence, including the early epidermotropic cells in Pautrier's
      microabscesses. This study demonstrates the potential of eMF-enriched genes,
      especially TOX, as molecular markers for histological diagnosis of eMF, which
      currently is a major diagnostic challenge.

PMID- 22377760
TI  - The cell cycle regulator protein 14-3-3sigma is essential for hair follicle
      integrity and epidermal homeostasis.
AB  - The 14-3-3sigma (Stratifin; Sfn) is a cell cycle regulator intimately involved in
      the program of epithelial keratinization. 14-3-3sigma is unique in that it is
      expressed primarily in epithelial cells and is frequently silenced in epithelial
      cancers. Despite its well-documented role as a cell cycle regulator and as a
      tumor suppressor, the function of 14-3-3sigma in the intricate balance of
      proliferation and differentiation in epithelial development is poorly understood.
      A mutation in 14-3-3sigma was found to be responsible for the repeated epilation
      (Er) phenotype. It has previously been shown that Sfn(+/Er) mice are
      characterized by repeated hair loss and regrowth, whereas Sfn(Er/Er) mice die at
      birth displaying severe oral fusions and limb abnormalities as a result of
      defects in keratinizing epithelia. Here we show that mice heterozygous for the 14
      3-3sigma mutation have severe defects in hair shaft differentiation, resulting in
      destruction of the hair shaft during morphogenesis. Furthermore, we report that
      the interfollicular epidermis and sebaceous glands are hyperproliferative,
      coincident with expanded nuclear Yap1 (Yes-associated protein 1)--a critical
      modulator of epidermal stem cell proliferation. We also report that hair follicle
      stem cells in the bulge cycle abnormally, raising important questions as to the
      role of 14-3-3sigma in the bulge.

PMID- 22377761
TI  - Genetic requirement for ADAM10 in severe Staphylococcus aureus skin infection.

PMID- 22377762
TI  - The use of human sweat gland-derived stem cells for enhancing vascularization
      during dermal regeneration.
AB  - Vascularization is a key process in tissue engineering and regeneration and
      represents one of the most important issues in the field of regenerative
      medicine. Thus, several strategies to improve vascularization are currently under
      clinical evaluation. In this study, stem cells derived from human sweat glands
      were isolated, characterized, seeded in collagen scaffolds, and engrafted in a
      mouse full skin defect model for dermal regeneration. Results showed that these
      cells exhibit high proliferation rates and express stem cell and differentiation
      markers. Moreover, cells responded to angiogenic environments by increasing their
      migration (P<0.001) and proliferation (P<0.05) capacity and forming capillary
      like structures. After seeding in the scaffolds, cells distributed homogeneously,
      interacting directly with the scaffold, and released bioactive molecules involved
      in angiogenesis, immune response, and tissue remodeling. In vivo, scaffolds
      containing cells were used to induce dermal regeneration. Here we have found that
      the presence of the cells significantly improved vascularization (P<0.001). As
      autologous sweat gland-derived stem cells are easy to obtain, exhibit a good
      proliferation capacity, and improve vascularization during dermal regeneration,
      we suggest that the combined use of sweat gland-derived stem cells and scaffolds
      for dermal regeneration might improve dermal regeneration in future clinical
      settings.

PMID- 22377764
TI  - CD70-CD27 interaction augments CD8+ T-cell activation by human epidermal
      Langerhans cells.
AB  - Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments
      exhibit functional differences in their induction of CD4+ T-cell and humoral
      immune responses; however, differences in the regulation of memory CD8+ T-cell
      responses by human skin DCs remain poorly characterized. We tested the capacity
      of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce
      antigen-specific cytokine production and proliferation of memory CD8+ cells.
      Although tumor necrosis factor-alpha-matured human DCs from both epidermal and
      dermal compartments showed efficient potential to activate CD8+ cells, LCs were
      constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as
      well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+
      T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27
      signaling demonstrated that superiority of CD8+ activation by epidermal LC is
      CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a
      central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC
      CD70 expression is important in enhancing immunity against cutaneous epithelial
      pathogens and cancer.

PMID- 22377763
TI  - Association of vitamin A and carotenoid intake with melanoma risk in a large
      prospective cohort.
AB  - Laboratory data suggest that intake of vitamin A and carotenoids may have
      chemopreventive benefits against melanoma, but epidemiological studies examining
      the association have yielded conflicting results. We examined whether dietary and
      supplemental vitamin A and carotenoid intake was associated with melanoma risk
      among 69,635 men and women who were participants of the VITamins And Lifestyle
      (VITAL) cohort study in western Washington. After an average of 5.84 years of
      follow-up, 566 incident melanomas were identified. Cox proportional hazards
      regression models were used to estimate hazard ratios (HRs) and 95% confidence
      intervals (CIs) for risk of melanoma associated with dietary, supplemental, and
      total vitamin A and carotenoid intake after adjusting for melanoma risk factors.
      Baseline use of individual retinol supplements was associated with a significant
      reduction in melanoma risk (HR: 0.60; 95% CI: 0.41-0.89). High-dose (>1,200 MUg
      per day) supplemental retinol was also associated with reduced melanoma risk (HR:
      0.74; 95% CI: 0.55-1.00), as compared with non-users. The reduction in melanoma
      risk was stronger in sun-exposed anatomic sites. There was no association of
      melanoma risk with dietary or total intake of vitamin A or carotenoids. Retinol
      supplementation may have a preventative role in melanoma among women.

PMID- 22377765
TI  - Transcutaneous gene gun delivery of hNC16A Induces BPAG2-specific tolerance.
AB  - Immune recognition and rejection of tissues expressing transfected genes is a
      major complication of gene replacement therapy for inherited genetic disorders.
      Owing to the high immunogenicity of human bullous pemphigoid antigen 2 (hBPAG2),
      the induction and maintenance of tolerance to this neo-antigen is essential to
      deliver the gene product to patients with epidermolysis bullosa junctionalis. In
      a skin grafting mouse model, we used gene gun transfection with a construct
      encoding hNC16A, the immunodominant domain of hBPAG2, to induce antigen-specific
      immune tolerance. Eighty percent of wild-type mice transfected with hNC16A showed
      long-term survival of skin grafts expressing hBPAG2. Tolerance was stable and
      transferable by T cells but not by B cells of tolerant mice to naive hosts. A
      dense Foxp3(+) regulatory T-cell (T(reg)) infiltrate was noticed in grafts of
      tolerant mice and depletion of these cells resulted in a loss of tolerance. Taken
      together, we show that long-lasting hBPAG2-specific tolerance was induced with
      gene gun delivery of hNC16A through a T(reg)-dependent mechanism. This is of
      relevance to patients undergoing gene therapy and has broader implications for
      the treatment of antigen-specific autoimmune diseases.

PMID- 22377766
TI  - MDM2 inhibitor nutlin-3a induces apoptosis and senescence in cutaneous T-cell
      lymphoma: role of p53.
AB  - P53 is rarely mutated in cutaneous T-cell lymphoma (CTCL) and is therefore a
      promising target for innovative therapeutic approaches. Nutlin-3a is an inhibitor
      of MDM2 (human homolog of murine double minute 2), which disrupts its interaction
      with p53, leading to the stabilization and activation of p53. To investigate the
      potential therapeutic use of nutlin-3a in CTCL, we screened CTCL lines Hut-78,
      SeAx, MyLa2000, Mac1, and Mac2a by measuring p53 levels after nutlin-3a
      treatment. In MyLa2000, Mac1, and Mac2a, we observed the increase in p53,
      indicating the fully functional p53. In the remaining cell lines, P53 mutation
      analysis identified a homozygous nonsense mutation (R196Stop in Hut-78) and a
      homozygous missense mutation (G245S in SeAx). In MyLa2000, Mac1, and Mac2a
      carrying wild-type P53, nutlin-3a induced apoptosis and senescence demonstrated
      by permanent G0/G1 cell-cycle block and expression of the senescence-associated
      beta-galactosidase. This effect was abolished in cells in which p53 was silenced
      by small interfering RNA. Sezary cells lack functional p53 and were resistant to
      nutlin-3a. However, nutlin-3a potentiated the efficacy of conventional
      chemotherapeutics not only in cells with intact p53 but also in Hut-78, SeAx, and
      Sezary cells. Thus, targeting p53 by nutlin-3a may constitute a therapeutic
      approach in CTCL because of increased apoptosis and senescence of tumor cells.

PMID- 22377767
TI  - Creams used by hand eczema patients are often contaminated with Staphylococcus
      aureus.

PMID- 22377768
TI  - Calpain4 is required for activation of HER2 in breast cancer cells exposed to
      trastuzumab and its suppression decreases survival and enhances response.
AB  - Overactivation of HER2 and crosstalk of other HER family members contribute to a
      survival pathway of breast cancer cells exposed to trastuzumab, the therapeutic
      inhibitor of HER2 and thus, decrease response and promote resistance. We have
      explored the involvement of the intracellular cysteine protease calpain4, the
      common partner of isoforms calpain1 and calpain2, in the regulation of cell
      survival and trastuzumab-response. Increase of calpain4 expression and isoform
      activities were detected in breast cancer cells and HER2-positive tumors.
      Molecular analyses of parent and resistant cells suggested that perturbation of
      regulations, induced by calpain4 and of activities of HER2 and HER3, was
      associated with trastuzumab-resistance. The suppression of calpain4 destabilized
      calpain1 and calpain2, however, did not prevent the activation of HER2 and HER3
      or cell proliferation in the absence of trastuzumab. To understand the
      significance, the survival of parent and trastuzumab-resistant cells in which
      calpain4 was suppressed, was assessed in the presence of trastuzumab; survival in
      each cell type was decreased and associated with a loss of HER2 and HER3
      activity. Taken together, by contributing to the activation and the crosstalk of
      HER2, calpain4 promotes the survival pathway of breast cancer cells, and
      therefore, its suppression enhances trastuzumab-response and decreases
      resistance.

PMID- 22377769
TI  - Antioxidant therapies: a potential role in perinatal medicine.
AB  - Pregnancies complicated by impaired placentation, acute severe reductions in
      oxygen supply to the fetus, or intrauterine infection are associated with
      oxidative stress to the mother and developing baby. Such oxidative stress is
      characterized as an upregulation in the production of oxidative or nitrative free
      radicals and a concomitant decrease in the availability of antioxidant species,
      thereby creating a state of fetoplacental oxidative imbalance. Recently, there
      has been a good deal of interest in the potential for the use of antioxidant
      therapies in the perinatal period to protect the fetus, particularly the
      developing brain, against oxidative stress in complications of pregnancy and
      birth. This review will examine why the immature brain is particularly
      susceptible to oxidative imbalance and will provide discussion on antioxidant
      treatments currently receiving attention in the adult and perinatal literature -
      allopurinol, melatonin, alpha-lipoic acid, and vitamins C and E. In addition, we
      aim to address the interaction between oxidative stress and the fetal
      inflammatory response, an interaction that may be vital when proposing
      antioxidant or other neuroprotective strategies.

PMID- 22377771
TI  - Demographic diversity, value congruence, and workplace outcomes in acute care.
AB  - Nursing scholars and healthcare administrators often assume that a more diverse
      nursing workforce will lead to better patient and nurse outcomes, but this
      assumption has not been subject to rigorous empirical testing. In a study of
      nursing units in acute care hospitals, the influence of age, gender, education,
      race/ethnicity, and perceived value diversity on nurse job satisfaction, nurse
      intent to stay, and patient satisfaction were examined. Support was found for a
      negative relationship between perceived value diversity and all outcomes and for
      a negative relationship between education diversity and intent to stay.
      Additionally, positive relationships were found between race/ethnicity diversity
      and nurse job satisfaction as well as between age diversity and intent to stay.
      From a practice perspective, the findings suggest that implementing retention,
      recruitment, and management practices that foster a strong shared value system
      among nurses may lead to better workplace outcomes.

PMID- 22377772
TI  - Interstitial pneumonitis after treatment with pemetrexed: a rare event?
AB  - BACKGROUND: Pneumonitis after pemetrexed has been rarely reported in conjunction
      with radiation therapy. METHODS: Two cases of pemetrexed-induced pneumonitis in
      different clinical settings and with unequal outcomes are discussed with a review
      of the literature. RESULTS: Two patients with stage IIIB non-small cell lung
      cancer developed interstitial lung disease after chemotherapy with pemetrexed.
      The first patient was previously treated with thoracic radiotherapy, and
      radiation pneumonitis was initially suspected. He died shortly after pemetrexed
      reexposition. The second patient developed pemetrexed-induced interstitial lung
      disease despite no prior radiotherapy. After discontinuation of pemetrexed and
      administration of steroids, pneumonitis resolved completely. CONCLUSION:
      Interstitial lung disease is a rare but potentially fatal side effect of
      pemetrexed. It occurs more often after radiotherapy but can also be encountered
      in the absence of radiotherapy. Reexposition to pemetrexed may lead to severe
      interstitial lung disease and even death and should be strictly avoided.

PMID- 22377773
TI  - Progressive external ophthalmoplegia in southwestern Finland: a clinical and
      genetic study.
AB  - BACKGROUND: Progressive external ophthalmoplegia (PEO) is a common phenotype of
      mitochondrial disease. Molecular etiologies include sporadic, large-scale
      deletions in mitochondrial DNA (mtDNA), multiple mtDNA deletions secondary to
      autosomal dominant or recessive mutations and mtDNA point mutations. METHODS: We
      studied the prevalence and clinical and genetic characteristics of PEO in a
      defined population in southwestern Finland. A total of 620 patients were first
      identified from the patient registry at the Turku University Hospital over an 18
      year period. The medical records of these patients were scrutinized, and those
      with clinical features compatible with PEO were ascertained. RESULTS: We
      identified 10 patients with possible PEO. The patients were examined clinically,
      and DNA was analyzed for mtDNA deletions and for the m.3243A>G and m.8344A>G
      mtDNA point mutations. The ANT1, PEO1, POLG1 and POLG2 genes were sequenced. We
      confirmed the clinical diagnosis of PEO in 6 patients. Large-scale mtDNA
      deletions were detected in 3 out of 6 PEO patients and mutations in the POLG1
      gene in 1 out of 6. We did not find any mutations in the ANT1, PEO1 or POLG2
      genes. CONCLUSIONS: Our results suggest that molecular investigation of patients
      with PEO, either sporadic or familial, should start with an analysis for mtDNA
      deletions, followed by an analysis of the POLG1 gene.

PMID- 22377774
TI  - Leisure activities alleviate depressive symptoms in nursing home residents with
      very mild or mild dementia.
AB  - OBJECTIVES: : To examine whether leisure activities can alleviate depressive
      symptoms among nursing home residents with very mild to mild dementia. METHODS: :
      A cluster-randomized open-label controlled design. Thirty-six residents with at
      least moderate depressive symptoms were randomized by home into three conditions
      mahjong (a.k.a. mah-jongg), tai chi, and handicrafts (placebo). Activities were
      conducted three times weekly for 12 weeks. Outcome measure was Geriatric
      Depression Scale (GDS) administered at baseline, posttreatment, and at 6 months.
      RESULTS: : Repeated-measures analysis of variance showed a group by time
      interaction on the GDS. Unlike control and tai chi participants whose scores
      remained relatively unchanged, the mahjong group reported a drop of 3.25 points
      (95% confidence interval: 1.00-5.50) on the GDS at posttreatment but gained back
      2.83 points (95% confidence interval: 1.95-5.47) at 6 months. Activity
      discontinuation might be the reason for depression to return to baseline.
      CONCLUSIONS: : Mahjong can lower depressive symptoms in those with mild dementia,
      but activity maintenance may be essential for long-term effects.

PMID- 22377775
TI  - The polymorphism of the ATP-binding cassette transporter 1 gene modulates
      Alzheimer disease risk in Chinese Han ethnic population.
AB  - BACKGROUND: Recent studies highlight a potential role of cholesterol metabolic
      disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine
      triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within
      proximity of linkage peaks on chromosome 9q influence AD and plays a key role in
      cellular cholesterol efflux in the brain. METHODS: We studied the role of R219K
      and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients
      and 349 comparisons of Chinese Han. Genotyping of R219K and V825I were performed
      by PCR-restriction fragment length polymorphism analysis. RESULTS: The genotype
      distribution of R219K was different with more RK in total AD group (chi(2) =
      8.705, df = 2, p = 0.013), late-onset AD (LOAD) group (chi(2) = 10.636, df = 2, p
      = 0.005), APOE non-epsilon4epsilon4 group (chi(2) = 9.900, df = 2, p = 0.007),
      and female AD group (chi(2) = 8.369, df = 2, p = 0.015). Logistic regression
      manifested the risk of AD increased in RK carriers in total AD group (Wald =
      6.102, df = 1, p = 0.014, odds ratio [OR]: 1.546, 95% confidence interval [95%
      CI]: 1.094-2.185), LOAD group (Wald = 7.746, df = 1, p = 0.005, OR: 1.921, 95%
      CI: 1.213-3.041), and APOE non-epsilon4epsilon4 group (Wald = 6.399, df = 1, p =
      0.011, OR: 1.586, 95% CI: 1.109-2.266). K allele (RK + KK) also increased the
      risk of AD compared with RR allele in LOAD group (Wald = 4.750, df = 1, p =
      0.029, OR: 1.619, 95% CI: 1.050-2.497). However, no discrepancy was found in
      V825I. In R219K, age at onset (AAO) was significantly lower by 4.9 years on
      average in patients of KK genotype than those of RK in APOE epsilon4 carrying
      group and higher by 5.5 years in patients of KK genotype than those of RR in APOE
      epsilon4 noncarrying group. In V825I, AAO was diseased by 4.3 years in II
      genotype compared with VV genotype in APOE epsilon4 noncarrying group and 3.4
      years in APOE epsilon4epsilon4 noncarrying group. CONCLUSION: The results
      indicated that the RK genotype or K allele (RK + KK) of R219K may relate to the
      development of AD in the east of China.

PMID- 22377776
TI  - Relative risk of cervical cancer in indigenous women in Australia, Canada, New
      Zealand, and the United States: a systematic review and meta-analysis.
AB  - We performed a systematic review and meta-analysis of cervical cancer risk in
      indigenous women in Australia, Canada, New Zealand, and the United States, in
      order to identify whether risks of cervical dysplasia, cervical cancer, and
      cervical cancer-related mortality are higher in indigenous relative to non
      indigenous populations. We identified 35 studies published in 1969-2008. In our
      findings, indigenous populations did not have an elevated risk of cervical
      dysplasia or carcinoma in situ relative to non-indigenous populations, but had
      elevated risks of invasive cervical cancer (pooled RR=1.72) and cervical cancer
      related mortality (pooled RR=3.45). There was a log-linear relationship between
      relative risk and disease stage. In conclusion, the indigenous women have a
      markedly higher risk of cervical cancer morbidity and mortality than non
      indigenous women, but no increased risk of early-stage disease, suggesting that
      structural, social, or individual barriers to screening, rather than baseline
      risk factors, are influencing poor health outcomes.

PMID- 22377777
TI  - Smokers' perceptions of smokeless tobacco and harm reduction.
AB  - Existing survey data indicate that most smokers are not receptive to harm
      reduction incentives of switching to smokeless tobacco (SLT). Little is known
      about the underlying reasons for these views. To explore smokers' perceptions of
      SLT, we conducted a focus group (eight in total) study of daily smokers between
      2009 and 2010 at the University of California, Irvine. We transcribed each 2-hour
      focus group verbatim and analyzed it using domain analysis. The discussions
      revealed several reasons why smokers are not receptive to SLT. First, smokers
      associated new spit-less SLT (that is, Snus) with historic images of chewing
      tobacco. Second, smokers viewed smoking as an incentive to take a break from
      their daily routine. Third, smokers expressed lack of control over nicotine
      delivery when using SLT, relative to cigarettes. These findings challenge tobacco
      manufacturers' strategies to market a smokeless alternative as a growing number
      of smoke-free policies are introduced.

PMID- 22377778
TI  - Replication and extension of the simplified modified rankin scale in 150 Chinese
      stroke patients.
AB  - BACKGROUND: Recently, a simplified modified Rankin Scale (mRS) questionnaire
      (smRSq) showed good reliability but has not been tested for its validity by its
      original creators. Our study aimed to test its reliability and validity in
      Chinese stroke patients. METHODS: Randomly chosen paired raters scored the smRSq,
      the conventional mRS, and the NIH Stroke Scale (NIHSS) face-to-face in 150
      hospitalized stroke patients. Inter-rater reliability and concurrent validity
      were assessed for this translated questionnaire. RESULTS: For inter-rater
      reliability of the smRSq, the overall agreement among the raters was 84%, the
      kappa was 0.79 (95% CI 0.72-0.87), and the kappaw was 0.91 (95% CI 0.88-0.94).
      For inter-rater reliability of the mRS, the overall agreement among the raters
      was 81%, the kappa was 0.75 (95% CI 0.67-0.83), and the kappaw was 0.88 (95% CI
      0.84-0.92). The agreement between the mRS and smRSq was 71%, kappa = 0.63 (95% CI
      0.54-0.71), and kappaw = 0.83 (95% CI 0.79-0.88). The correlation between the
      NIHSS and the smRSq (concurrent validity) was moderate (Spearman's correlation
      coefficient 0.70, p < 0.0001). CONCLUSIONS: Our results confirm the value of the
      smRSq in the assessment of stroke functional outcome in China. As this is a novel
      stroke tool, further validations are needed.

PMID- 22377779
TI  - Supraorbitary to infraorbitary nerve transfer for restoration of midface
      sensation in face transplantation: cadaver feasibility study.
AB  - BACKGROUND: The collected experience from facial allotransplantations has shown
      that the recovery of sensory function of the face graft is unpredictable.
      Unavailability of healthy donor nerves, especially in central face defects may
      contribute to this fact. Herein, the technical feasibility of transferring the
      supraorbitary nerve (SO) to the infraorbitary nerve (IO) in a model of central
      facial transplantation was investigated. METHODS: Five heads from fresh cadavers
      were dissected with the aid of 3* loupe magnification. Measurements of the
      maximum length of dissection of the SO nerve through a supraciliary incision and
      the IO nerve from the skin of the facial flap to the infraorbital foramen were
      performed. The distance between supraorbital and infraorbital foramens and the
      calibers of both nerves were also measured. In all dissections, we simulated a
      central allotransplantation procedure and assessed the feasibility of directly
      transferring the SO to the IO nerve. RESULTS: The average maximum length of
      dissection for the IO and SO nerve was 1.4 +/- 0.3 cm and 4.5 +/- 1.0 cm,
      respectively. The average distance between the infraorbital and supraorbital
      foramina was 4.6 +/- 0.3 cm. The average calibers of the nerves were of 1.1 +/-
      0.2 mm for the SO nerve and 2.9 +/- 0.4 mm for the IO nerve. We were able to
      perform tension-free SO to IO nerve coaptations in all specimens. CONCLUSION: SO
      to IO nerve transfer is an anatomically feasible procedure in central facial
      allotransplantation. This technique could be used to improve the restoration of
      midfacial sensation by the use of a healthy recipient nerve in case of the
      recipient IO nerves are not available secondary to high-energy trauma.

PMID- 22377781
TI  - Is long-term prognosis of frontotemporal lobar degeneration predictable by
      neuroimaging? Evidence from a single-subject functional brain study.
AB  - Prediction of survival in frontotemporal lobar degeneration (FTLD) is guesswork.
      The aim of the present study was to evaluate whether SPECT scan may be useful to
      predict prognosis of long term survival in FTLD patients. A cohort of 125
      patients with FTLD who underwent brain SPECT scan at the time of enrollment and
      who were further followed up for at least one year were considered. In each
      subject, volume of interests (VOIs) covering frontotemporal and parietal regions,
      bilaterally, were drawn. Principal component analysis (PCA) was applied on VOIs,
      and a Cox regression model was carried out to find out best predictors of
      survival. A two-pattern PCA solution was chosen, explaining more than 70% of
      variance, and "frontal" PC1 and "temporal" PC2 components were identified. The
      frontal PC1 was associated with higher rate of faster progression (HR = 2.06, 95%
      CI = 1.23-3.44, p = 0.006 for univariate model, and HR = 1.85, 95% CI = 1.04
      3.28, p = 0.03 for multivariate model). In particular, right orbitofrontal cortex
      showed the higher loadings in PC1; the worse the scores of this region the
      shorter the survival was reported. We suggest that SPECT imaging, beyond a
      helpful tool in diagnostic assessment, may be an easily and accessible marker of
      disease outcome in FTLD. Further studies considering structural neuroimaging are
      warranted.

PMID- 22377780
TI  - Markers of cholesterol metabolism in the brain show stronger associations with
      cerebrovascular disease than Alzheimer's disease.
AB  - Cholesterol metabolism is believed to play a role in the development of
      Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S
      hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol
      (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have
      been associated with AD. We investigated whether oxysterols were associated with
      markers of cerebrovascular disease prior to the onset of cognitive impairment.
      Oxysterols were quantified in 105 participants (average age: 80 +/- 4 years) from
      the Pittsburgh Cardiovascular Health Study Cognition Study who remained
      cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual
      cognitive assessment for incident AD and mild cognitive impairment made by
      consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were
      associated with age, gender, the presence of high grade white matter
      hyperintensities, and brain infarcts on prior MRI. Participants with higher
      plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to
      develop incident cognitive impairment over 8 years of follow-up. Higher levels of
      24-OHC suggest increased cholesterol metabolism occurring in the brains of
      participants with cerebrovascular disease prior to the onset of cognitive
      impairment. Measurement of oxysterols may provide information about cholesterol
      metabolism and brain disease over the cognitive impairment process.

PMID- 22377782
TI  - Depressive symptoms, antidepressant use, and brain volumes on MRI in a population
      based cohort of old persons without dementia.
AB  - We examined whether late-life depression, including depressive symptoms and
      antidepressant use, was associated with smaller total brain volume, smaller
      hippocampal volume, and larger white matter hyperintensity (WMH) volume in a
      large community-based cohort of old persons without dementia. Within the
      Washington/Hamilton Height-Inwood Columbia Aging Project (WHICAP), a community
      based cohort study in northern Manhattan, 630 persons without dementia (mean age
      80 years, SD = 5) had volumetric measures of the total brain, hippocampus, and
      WMH at 1.5 Tesla MRI and data on current depression, defined as a score of 4 or
      higher on the 10-item Center for Epidemiologic Studies-Depression (CES-D) scale,
      or use of antidepressants. Multiple linear regression analyses adjusted for age,
      gender, ethnicity, education, cardiovascular disease history, and MRI parameters
      showed that subjects with current depression had smaller relative total brain
      volume (B = -0.86%; 95% CI -1.68 to -0.05%; p < 0.05), smaller relative
      hippocampal volume (B = -0.07 ml; 95% CI -0.14 to 0.00 ml; p = 0.05), and larger
      relative WMH volume (natural logtransformed B = 0.19 ml; 95% CI 0.02 to 0.35 ml;
      p < 0.05). When examined separately, antidepressant use was significantly
      associated with smaller total brain, smaller hippocampal, and larger WMH volume,
      while high CES-D scores were not significantly associated with any of the brain
      measures, although the direction of association was similar as for antidepressant
      use. With the caveat that analyses were cross-sectional and we had no formal
      diagnosis of depression, our findings suggest that in this community-based sample
      of old persons without dementia, late-life depression is associated with more
      brain atrophy and more white matter lesions, which was mainly driven by
      antidepressant use.

PMID- 22377783
TI  - Visuomotor impairment in early-stage Alzheimer's disease: changes in relative
      timing of eye and hand movements.
AB  - Although memory complaints are one of the first clinical symptoms in patients
      with Alzheimer's disease (AD), damage to the parietal lobe, a key structure in
      the visuomotor coordination network, was recently identified in early-stage AD.
      The aim of this study was to quantify visuomotor coordination in patients with
      probable AD and to compare their visuomotor performance with controls using five
      eye-hand coordination tasks of variable complexity. Eye and hand movements were
      measured in 16 AD patients and 18 controls. The measurement setup consisted of a
      touch screen, an eye-tracking device, and a motion capturing system. We
      investigated eye-hand coordination by quantifying absolute and relative latencies
      of eye and hand movements and by analyzing eye and hand kinematics. We found that
      AD patients need significantly more time to initiate and execute goal-directed
      hand movements. AD patients are also unable to suppress reflexive eye and, to a
      lesser extent, hand movements. Furthermore, AD patients use a stepwise approach
      of eye and hand movements to touch a sequence of stimuli, whereas controls more
      often show an anticipatory approach. The impairments in reflex suppression of eye
      and hand movements, and changes in relative timing of eye-hand coordination, in
      AD patients support the notion that cortical networks involving the posterior
      parietal cortex are affected at an early disease-stage. It also suggests that the
      problems of AD patients to perform daily activities that require eye-hand
      coordination are not only caused by cognitive decline, but also by degeneration
      of neural networks involved in visuomotor coordination.

PMID- 22377784
TI  - Calcium channel blockers and Alzheimer's disease: potential relevance in
      treatment strategies of metabolic syndrome.
AB  - Midlife hypertension is a risk factor for late onset Alzheimer's disease (AD) and
      it is one of the components of metabolic syndrome (MetS). Observational studies
      and some cardiovascular disease-related clinical trials suggest that
      antihypertensive treatment reduced the incidence and progression of AD. Calcium
      channel blockers (CCBs), one of the more commonly used treatments for
      hypertension, target voltage-gated calcium channels (VGCCs) which are found on
      neurons in the brain where calcium regulation is very important in both learning
      and memory. Amyloid-beta (Abeta) peptide, one of the main pathological hallmarks
      of AD, causes increases to intracellular calcium via VGCCs, which in turn leads
      to further increases in Abeta production. Memantine, a current treatment used in
      AD, exerts some of its beneficial effects by blocking calcium entry into neurons.
      We explore the possibility of whether CCBs acting in the brain may delay the
      onset and progression of AD and thus may inform treatment regimes in people with
      MetS.

PMID- 22377788
TI  - Anogenital malignancies in women after renal transplantation over 40 years in a
      single center.
AB  - BACKGROUND: Renal transplant recipients have an increased risk to develop human
      papillomavirus (HPV)-related anogenital malignancies. A clinical overview of
      female anogenital posttransplantation malignancies and possible multifocal
      premalignancies over a period of 40 years renal transplantation is presented.
      Additionally, the genotype-specific prevalence of HPV in these (pre)malignancies
      was investigated. METHODS: Data of 1023 women, who underwent a renal
      transplantation between 1968 and 2008, were collected. Clinical data of all
      female renal transplant recipients who developed anogenital malignancies were
      retrospectively analyzed. The histology, cytology, and distribution of genotype
      specific HPV infections were analyzed in all primary anogenital tumors and
      possible (multifocal) premalignancies. RESULTS: Sixteen anogenital malignancies
      (1.6%) were found: vulva (n=6), cervix (n=5), and anus (n=5). Twelve of 16
      patients never had a cervical smear before transplantation. The median interval
      between transplantation and diagnosis of malignancy was 136 months (range, 16-288
      months). High-risk HPV was detected in 91.7% of investigated lesions, HPV subtype
      16 predominated (54.5%). Four of seven patients with two distinct anogenital
      lesions had different HPV types in the lesions. CONCLUSIONS: A high number of
      anogenital malignancies developed in our cohort, which are nearly all caused by
      HPV. Multifocal lesions within one patient frequently contained different high
      risk HPV genotypes in both lesions. Our results underline the importance of
      anogenital screening and monitoring before and periodically after renal
      transplantation to prevent morbidity and mortality from anogenital malignancies.

PMID- 22377789
TI  - Deficient long-term response to pandemic vaccine results in an insufficient
      antibody response to seasonal influenza vaccination in solid organ transplant
      recipients.
AB  - BACKGROUND: Little is known about the long-term antibody response to the 2009
      H1N1 vaccine in solid organ transplant recipients (SOTR) and its clinical
      repercussion on the efficacy of following 2010-2011 influenza vaccine. METHODS:
      We performed a multicenter prospective study in SOTR receiving one dose of the
      nonadjuvant 2010-2011 seasonal influenza vaccine and determined the immunological
      response at 5 weeks after vaccination. RESULTS: One hundred SOTR were included.
      Long-term antibody titers to the previous vaccine were only detected in one third
      of the patients. Patients with baseline titers had significantly higher
      seroprotection for the 2009-H1N1 strain (100% vs. 73%, relative risks [RR] 1.37,
      95% confidence intervals [CI] 1.19-1.57; P=0.006), for H3N2 strain (100% vs.
      62.2%, RR 1.61, 95% CI 1.36-1.90; P=0.005), and for B strain (100% vs. 69%;
      P=0.02). The seroconversion rate in patients with baseline titers was 90.9% vs.
      73% (RR 2.97, 95% CI 0.75-11.74; P=0.07) for the 2009-H1N1 strain, 92.2% vs.
      62.2% (RR 5.29, 95% CI 0.8-35.7; P=0.02) for the H3N2 strain, and 58.3% vs. 69%
      (P=0.45) for the B strain. CONCLUSIONS: SOTR response to the 2010-2011 influenza
      vaccine was not optimal. The response was related to baseline titers; however,
      most of the patients did not exhibit detectable antibodies at vaccination lacking
      long-term response. New strategies are necessary to improve vaccination efficacy.

PMID- 22377790
TI  - Anemia after kidney transplantation; its prevalence, risk factors, and
      independent association with graft and patient survival:  a time-varying
      analysis.
AB  - INTRODUCTION: Posttransplant anemia and its association with transplant outcomes
      have not been properly studied. METHODS: We examined 530 renal allograft
      recipients transplanted at our center and followed up for 31.0+/-14.1 months.
      Hemoglobin (Hb), serum bicarbonate, and creatinine; use of erythropoiesis
      stimulating agent (ESA) and iron; and immunosuppressive regimen data were
      obtained at multiple time points during 24-month posttransplant. RESULTS: The
      overall prevalence of anemia was 89.4% at the time of transplant, dropping to
      49.2% at 1 year and 44.3% at 2 years. ESA use decreased from 25.6% at 1 month to
      8.23% at 24 months, only in 30.9% to 51.2% with severe anemia; 21.0% to 29.2%
      received iron supplements. Factors independently predictive of Hb included male
      gender (beta=0.64, P<0.001, confidence interval [CI]: 0.45-0.82), estimated
      glomerular filtration rate (beta=0.21 per 10 mL/min/1.73 m, P<0.001; CI: 0.16
      0.27), bicarbonate (beta=0.4 per 10 mmol/L increase, P<0.001; CI: 0.31-0.85),
      using angiotensin-converting enzyme inhibitor/angiotensin receptor blocker
      (beta=0.36, P<0.001; CI: 0.16-0.55), African American race (beta=-0.34, P=0.001,
      CI:-0.54 to -0.14), iron (beta=-0.28, P=0.003, CI:-0.47 to -0.09) and ESA use
      (beta=-0.73, P<0.001, CI:-0.93 to -0.52), and prednisone (beta=-0.46, P<0.001,
      CI:-0.71 to -0.22 for >10 mg/day vs. none). Using a competing-risk regression
      model, Hb less than 9 in men and less than 8 in women, was associated with 5.25
      fold higher risk of death-censored graft loss compared with no anemia (adjusted,
      P=0.005, CI: 1.7-16.7). Degree of anemia also remained significantly associated
      with risk of death (hazard ratio [HR]: 2.2, P<0.1, CI: 0.9-5.6 for grade 2; HR:
      3.9, P=0.009, CI: 1.4-10.8 for grade 3; and HR: 4.8, P=0.08, CI: 1.5-15.4 for
      grade 4, all vs. grade 0). CONCLUSION: We showed that posttransplant anemia is
      common, and ESA/iron use remains suboptimal, and Hb is independently associated
      with graft failure and mortality.

PMID- 22377791
TI  - Association of genetic polymorphisms of interleukins with new-onset diabetes
      after transplantation in renal transplantation.
AB  - BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious
      metabolic complication. Although beta-cell dysfunction is considered the main
      contributing factor in the development of NODAT, the precise pathogenesis has not
      been identified. Although several cytokines have been suggested to be involved in
      the inflammation of islet beta cells in diabetes mellitus, only rarely have
      studies examined beta-cell dysfunction in NODAT. Therefore, we examined the
      association between NODAT and 18 single nucleotide polymorphisms (SNPs) located
      within the 10 genes of interleukins (IL) or their receptors, which might be
      related with beta-cell dysfunction after kidney transplantation. METHODS: A total
      of 306 renal transplants recipients were included without a history of diabetes.
      We analyzed the association between NODAT development and a panel of 18 SNPs
      within 10 genes of IL or their receptors. RESULTS: In terms of allele
      frequencies, rs2069763*T (IL-2), rs1494558*A and rs2172749*C (IL-7R), and
      rs4819554*A (IL-17R) were significantly higher in patients with NODAT. Eleven
      SNPs among 18 (61.1%) were significantly associated with NODAT development after
      adjusting for age, sex, and tacrolimus usage. They include IL-1B (rs3136558), IL
      2 (rs2069762), IL-4 (rs2243250, rs2070874), IL-7R (rs1494558, rs2172749), IL-17RE
      (rs1124053), IL-17R (rs2229151, rs4819554), and IL-17RB (rs1043261, rs1025689).
      CONCLUSIONS: The data suggest that inflammation of islet beta cells might play a
      crucial role in the pathogenesis of NODAT in renal transplantation recipients. In
      particular, significant variations of IL-7R, IL-17E, IL-17R, and IL-17RB, which
      was recently reported to be associated with type 1 diabetes mellitus, could be
      associated with the pathogenesis of NODAT in renal transplant recipients.

PMID- 22377792
TI  - Distinct oligoclonal T cells are associated with graft versus host disease after
      stem-cell transplantation.
AB  - BACKGROUND: In patients with hematologic malignancies who receive stem-cell
      transplantation, donors' T cells can recognize minor histocompatibility antigens
      on recipient cells and generate an objective response against the tumor. However,
      a major side effect of such therapy is graft-versus-host disease (GVHD). The
      purpose of this study was to characterize distinct T-cell clones that were
      frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects.
      METHODS: We hypothesized that distinct GVHD-associated T-cell clones can be
      identified during the disease progression. To test this, we conducted comparative
      analysis of T-cell receptor (TCR) Vbetas in donor-recipient pairs of patients
      with GVHD versus those with GVHD-free and relapse-free survival using
      quantitative reverse-transcriptase polymerase chain reaction and spectratyping
      analyses. RESULTS: We identified three sets of T-cell clones that were either
      frequently involved in GVHD (TCR Vbeta4, 11, and 23) or GVT effect (TCR Vbeta9,
      16, and 20), or were increased at the time of GVHD and GVT effects in a patient
      specific manner (TCR Vbeta2, 3, 7, 12, 15, and 17). Spectratyping analysis showed
      restricted clonality of the identified TCR Vbetas. Polymerase chain reaction
      analysis also confirmed the presence of GVHD-associated T-cell clones at the site
      of the disease. CONCLUSIONS: These data suggest that GVHD- and GVT-associated
      clones can be distinguished by molecular analysis of TCR Vbeta to develop
      targeted therapy for GVHD.

PMID- 22377793
TI  - Melatonin improves inflammatory cytokine profiles in lung inflammation associated
      with sleep deprivation.
AB  - Sleep disturbance has become an endemic behavior in modern countries, and its
      prevalence has also increased. Even a subtle sleep deficiency is related to
      health problems. Particularly, patients with pulmonary disease often complain of
      insomnia. We recently showed that sleep deprivation (SD) exacerbates existing
      acute lung inflammation, and that melatonin treatment attenuates it via anti
      apoptotic and anti-oxidant action. In order to reinforce our previous report, the
      present study was designed to evaluate pro-inflammatory mediators in acute lung
      inflammation in SD mice. In addition, we investigated the infiltration of
      inflammatory cells into the lungs. Twenty-five ICR mice were divided into 5
      groups (n=5/group): control, SD, lipopolysaccharide (LPS), LPS + SD and LPS + SD
      + melatonin. The SD mice were deprived of sleep for 96 h in a multiplatform water
      bath. LPS (5 mg/kg) and melatonin (5 mg/kg) were administered on day 2. The mice
      were sacrificed on day 3, and serum and bronchoalveolar lavage (BAL) fluid were
      collected. The serum levels of inflammatory cytokines were increased in the LPS +
      SD group. Interleukin-6, tumor necrosis factor-alpha and interferon-gamma levels
      were also increased in BAL fluid in the LPS + SD group. Melatonin reduced
      inflammatory mediators in the serum and BAL fluid. The accumulation of leukocytes
      in the LPS and LPS + SD mice was elevated, however, melatonin inhibited the
      recruitment of inflammatory cells (p<0.05). Lymphocytes in the BAL fluid of the
      LPS + SD group were increased, and macrophage levels were decreased; however, the
      increment was attenuated by melatonin administration (p<0.05). In conclusion,
      this study indicates that melatonin has a protective effect against lung
      inflammation associated with SD.

PMID- 22377794
TI  - The chemistry of localized singlet 1,3-diradicals (biradicals): from putative
      intermediates to persistent species and unusual molecules with a pi-single bonded
      character.
AB  - Localized singlet diradicals (biradicals) are key intermediates in chemical
      reactions involving homolytic bond-cleavage and formation processes. The
      molecular structure and electronic structure had been historically elusive due to
      the short-lived character of the reactive intermediates. In the last 15 years, a
      significant development of singlet diradical chemistry was achieved after the
      pioneering findings of long-lived singlet diradicals. In this tutorial review,
      the recent development of localized singlet diradical chemistry is summarized and
      discussed. The following subjects are included (a) the mechanism by which the
      ground state spin-multiplicity of localized 1,3-diradicals is controlled; (b) the
      substituent and heteroatom effect on the most stable electronic configuration of
      the singlet 1,3-diradicals, type-1 versus type-2; (c) the molecular design for
      the long-lived singlet ground state diradicals; (d) the generation and
      characterization of the singlet diradicals; and (e) the future prospects.

PMID- 22377795
TI  - Mechanical properties of ethylcellulose oleogels and their potential for
      saturated fat reduction in frankfurters.
AB  - Ethylcellulose has been recently shown to be an excellent organogelator for
      vegetable oils. The resulting gels maintain the fatty acid profile of the
      vegetable oil used, but posses a solid-like structure that can be useful for the
      replacement of saturated fats in food products. Texture profile analysis and the
      back extrusion technique were used to assess the mechanical properties of canola,
      soybean, and flaxseed oil oleogels consisting of 10% ethylcellulose and 90%
      vegetable oil. Oils with a higher degree of unsaturation were shown to produce
      harder gels. Oleogels containing ethylcellulose of three molecular weights and
      reduced polymer concentrations from 4-10% ethylcellulose were also tested using
      the back extrusion technique, resulting in an increase in gel strength as polymer
      concentration and molecular weight increased. Therefore, oleogel strength was
      shown to be dependant on polymer molecular weight, concentration, and the fatty
      acid composition of the vegetable oil. Scanning electron microscopy was also used
      to provide a greater understanding of the gel's microstructure. In addition,
      frankfurters were made using canola oil oleogels to assess the possibility for
      replacement of the more highly saturated animal fat in such a product. Cooked
      frankfurters made with oleogels showed no significant differences in chewiness or
      hardness compared to the control products made with beef fat. These results
      provide the first in-depth characterization of ethylcellulose oleogels, and could
      potentially aid in the design/manufacture of ethylcellulose oleogels with
      specific textural properties to replace saturated fat in a variety of food
      products.

PMID- 22377797
TI  - Skin cancer and other cutaneous disorders in liver transplant recipients.
AB  - Patients who have received liver transplant are at increased risk of skin
      complications due to long-term immunosuppression regimen. The aim of this study
      was to analyze the incidence and risk factors of skin complications in liver
      transplant patients. We analyzed 161 liver transplant recipients. The mean age at
      transplantation was 47.4 years. Mean follow-up was 6 years. Seventy-one percent
      of patients presented with skin complications, including aestethic alterations,
      infections, precancerous lesions and malignancies, which represented 57%, 43%,
      18% and 9%, respectively. Risk factors were: age at transplantation >= 45 years,
      immunosuppressive therapy with cyclosporine, and phototype II and III. Our study
      indicates that although liver transplant recipients are at greater risk of
      developing skin complications compared to the general population, the risk is
      lower than for other solid organ transplants, particularly for premalignant and
      malignant lesions.

PMID- 22377796
TI  - Two-year randomized, placebo-controlled study of black currant anthocyanins on
      visual field in glaucoma.
AB  - AIM: To examine the influence of the black currant anthocyanins (BCACs) on the
      disease progression of open-angle glaucoma (OAG), a randomized, placebo
      controlled, double-masked trial was made in 38 patients with OAG treated by
      antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19)
      were orally administered once daily for a 24-month period. Systemic blood
      pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by
      laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were
      measured during the 24-month period. RESULTS: As a main outcome measurement, we
      evaluated the difference between the groups in MD deterioration in the eye with a
      better MD from the trial's baseline through 24 months. A statistically
      significant difference was observed between the treatment groups in mean change
      from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon
      administration of BCACs, the ocular blood flows during the 24-month observational
      period increased in comparison with placebo-treated patients. However, no
      significant changes were observed in systemic and ocular conditions including IOP
      during the 24-month period. CONCLUSIONS: Our results suggest that oral
      administration of BCACs may be a safe and promising supplement for patients with
      OAG in addition to antiglaucoma medication.

PMID- 22377798
TI  - Solitary sclerotic fibroma of the skin: a possible clue for Cowden syndrome.

PMID- 22377799
TI  - Living well with medical comorbidities: a biopsychosocial perspective.
AB  - OBJECTIVES: We take a biopsychosocial perspective on age-related diseases by
      examining psychological correlates of having multiple chronic conditions and
      determining whether positive psychological functioning predicts advantageous
      profiles of biological risk factors. METHOD: Respondents to the national survey
      of Midlife in the United States who participated in clinical assessments of
      health and biological processes (n = 998) provided information on chronic medical
      conditions and multiple domains of psychological functioning. Serum
      concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) were
      determined from fasting blood samples. RESULTS: Life satisfaction declined with
      increasing comorbidity while negative affect increased. In contrast, positive
      affect, purpose in life, and positive relations with others were unrelated to
      comorbidity status. Significant interactions showed that although IL-6 and CRP
      increased with increasing number of chronic conditions, respondents with higher
      levels of purpose in life, positive relations with others, and (in the case of
      CRP) positive affect had lower levels of inflammation compared with those with
      lower well-being scores. DISCUSSION: The results suggest that many older adults
      with medical comorbidities maintain high levels of positive psychological
      functioning that are in turn linked to better profiles of biological disease
      risk.

PMID- 22377800
TI  - Differential sleep-wake sensitivity of gonadotropin-releasing hormone secretion
      to progesterone inhibition in early pubertal girls.
AB  - CONTEXT: Early pubertal luteinizing hormone (LH), and by inference gonadotropin
      releasing hormone (GnRH), pulse secretion is marked by high nocturnal but low
      daytime frequency; however, the underlying mechanisms remain unclear. Plasma
      concentrations of progesterone, the major regulator of GnRH frequency in women,
      increase in the early morning in early pubertal girls and may help slow daytime
      GnRH frequency. OBJECTIVE: To evaluate the effect of progesterone on LH pulse
      frequency in early to mid-pubertal girls. DESIGN: Controlled interventional
      study. SETTING: General clinical research center. PARTICIPANTS: Eighteen non
      obese, non-hyperandrogenemic Tanner 1-3 girls. INTERVENTION: Twelve-hour (19:00
      07:00 h) blood sampling with or without oral progesterone administration (25-50
      mg at 16:00 and 20:00 h). MAIN OUTCOME MEASURE: LH pulse frequency. RESULTS:
      Girls receiving progesterone (n = 5) exhibited lower 12-hour LH pulse frequency
      than controls (n = 13), but this difference was not statistically significant
      (average interpulse intervals 196.0 +/- 61.9 and 160.4 +/- 67.1 min,
      respectively; p = 0.2793). In contrast to controls, however, girls receiving
      progesterone exhibited no LH pulses during waking hours (19:00-23:00 h; estimated
      interpulse interval 326.0 +/- 52.7 vs. 212.0 +/- 120.9 min; p = 0.0376), while
      nighttime (23:00-07:00 h) interpulse intervals were similar (174.8 +/- 62.0 vs.
      167.5 +/- 76.9 min, respectively; p = 0.7750). CONCLUSIONS: Exogenous
      progesterone acutely suppressed daytime, but not nocturnal, LH pulse frequency in
      early to mid-pubertal girls, suggesting that GnRH pulse frequency is
      differentially regulated by progesterone depending on sleep status.

PMID- 22377801
TI  - Ionic liquid pillar[5]arene: its ionic conductivity and solvent-free complexation
      with a guest.
AB  - A room-temperature ionic liquid containing macrocyclic compound pillar[5]arene in
      its core was synthesized. The ionic liquid showed high thermal stability,
      moderate ionic conductivity and solvent-free complexation ability with the guest
      tetracyanoethylene.

PMID- 22377802
TI  - Polymicrobial challenges to Koch's postulates: ecological lessons from the
      bacterial vaginosis and cystic fibrosis microbiomes.
AB  - Koch's postulates have shaped our understanding of infectious diseases; however,
      one of the tangential consequences of them has been the emergence of a
      predominantly monomicrobial perspective concerning disease aetiology. This
      orthodoxy has been undermined by the growing recognition that some important
      infectious diseases have a polymicrobial aetiology. A significant new development
      in our understanding of polymicrobial infections is the recognition that they
      represent functional ecosystems and that to understand such systems and the
      outcome and impact of therapeutic interventions requires an understanding of how
      these communities arise and develop. Therefore, it is timely to explore what we
      can learn from other fields. In particular, ecological theory may inform our
      understanding of how polymicrobial communities assemble their structure and their
      dynamics over time. Such work may also offer insights into how such communities
      move from stable to unstable states, as well as the role of invasive pathogens in
      the progression of the disease. Ecological theory offers a theoretical framework
      around which testable hypotheses can be developed to clarify the polymicrobial
      nature and dynamics of such infections in the face of environmental change and
      therapeutic interventions.

PMID- 22377803
TI  - Extracellular ATP induces P2X7-dependent nicotinamide phosphoribosyltransferase
      release in LPS-activated human monocytes.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD
      biosynthesis, has recently been identified as a novel mediator of innate
      immunity. In the present study, we report that treatment of LPS-primed monocytes
      with ATP greatly enhanced the secretion of NAMPT in a time- and concentration
      dependent manner without displaying any cytotoxic effect. NAMPT release was
      suppressed by pretreatment with the P2X(7) receptor (P2X(7)R) inhibitors oxidized
      ATP (oxATP) and KN-62, indicating the engagement of P2X(7)Rs. Furthermore,
      P2X(7)R was found to be involved in mediating cell permeability caused by the
      addition of ATP. To define a role of endogenous ATP in NAMPT secretion, LPS
      primed monocytes were incubated in the presence of oxATP and KN-62, as well as
      the ATP-hydrolyzing enzymes apyrase and hexokinase. With the exception of oxATP,
      neither substance led to a decrease in NAMPT release, suggesting that
      autocrine/paracrine ATP is unlikely to be responsible for the LPS-induced release
      of NAMPT. In conclusion, the enhanced release of NAMPT by extracellular ATP
      described here indicates the requirement of a second stimulus for the efficient
      secretion of NAMPT. This mode of secretion, which also applies to IL-1beta, might
      represent a general mechanism for the release of leaderless secretory proteins at
      locally restricted sites.

PMID- 22377804
TI  - An international registry on autoinflammatory diseases: the Eurofever experience.
AB  - OBJECTIVE: To report on the demographic data from the first 18 months of
      enrollment to an international registry on autoinflammatory diseases in the
      context of the Eurofever project. METHODS: A web-based registry collecting
      baseline and clinical information on autoinflammatory diseases and related
      conditions is available in the member area of the PRINTO web-site. Anonymised
      data were collected with standardised forms. RESULTS: 1880 (M:F=916:964)
      individuals from 67 centers in 31 countries have been entered in the Eurofever
      registry. Most of the patients (1388; 74%), reside in western Europe, 294 (16%)
      in the eastern and southern Mediterranean region (Turkey, Israel, North Africa),
      106 (6%) in eastern Europe, 54 in Asia, 27 in South America and 11 in Australia.
      In total 1049 patients with a clinical diagnosis of a monogenic autoinflammatory
      diseases have been enrolled; genetic analysis was performed in 993 patients
      (95%): 703 patients have genetically confirmed disease and 197 patients are
      heterozygous carriers of mutations in genes that are mutated in patients with
      recessively inherited autoinflammatory diseases. The median diagnosis delay was
      7.3 years (range 0.3-76), with a clear reduction in patients born after the
      identification of the first gene associated with autoinflammatory diseases in
      1997. CONCLUSIONS: A shared online registry for patients with autoinflammatory
      diseases is available and enrollment is ongoing. Currently, there are data
      available for analysis on clinical presentation, disease course, and response to
      treatment, and to perform large scale comparative studies between different
      conditions.

PMID- 22377805
TI  - Realignment treatment for medial tibiofemoral osteoarthritis: randomised trial.
AB  - OBJECTIVES: The objective of this 30-week randomised crossover trial was to
      determine whether a multi-modal realignment treatmentwould be successful in
      relieving pain and improving function among persons with medial tibiofemoral
      osteoarthritis (OA). METHODS: The authors conducted a double-blind randomised
      crossover trial of a multi-modal realignment treatment for medial tibiofemoral
      OA. Trial participants met American College of Rheumatology criteria for OA, with
      knee pain, aching or stiffness on most days of the past month and radiographic
      evidence of a definite osteophyte with predominant medial tibiofemoral OA. The
      authors tested two different treatments: (A) control treatment consisting of a
      neutral knee brace (no valgus angulation), flat unsupportive foot orthoses and
      shoes with a flexible mid-sole; and (B) active treatment consisting of a valgus
      knee brace, customised neutral foot orthoses and shoes designed for motion
      control. For each subject, the trial lasted 30 weeks, including 12 weeks each of
      active treatment and control treatment separated by a 6-week washout period. The
      primary outcome of the linear regression model was change in knee pain and
      function, as assessed by the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). RESULTS: 80 participants with medial tibiofemoral
      OA were randomised. Their mean age was 62 years, their mean body mass index was
      34 kg/m(2) and their mean WOMAC Pain score was 9.2 (0-20 scale). There was no
      evidence of a carryover effect. The regression model demonstrated that the mean
      difference in pain between the active treatment and the control treatment was 
      1.82 units (95% CI -3.05 to -0.60; p=0.004) on the WOMAC Pain scale, indicating a
      small but statistically significant decrease in pain with the multi-modal active
      treatment. For WOMAC Function, the realignment intervention had a non-significant
      effect on function, with a -2.90 unit decrease (95% CI -6.60 to 0.79) compared
      with the control condition (p=0.12). CONCLUSION: Multi-modal realignment
      treatment decreases pain in persons with medial tibiofemoral OA.

PMID- 22377806
TI  - Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis.
AB  - OBJECTIVE: To assess the correlation between cognitive impairment and overall vs
      regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI
      tractography in multiple sclerosis (MS). METHODS: Brain dual-echo, T1-weighted,
      and DT MRI data were acquired from 82 patients with MS. DT tractography was used
      to produce maps of white matter (WM) tracts involved in cognition. The sensory
      thalamocortical projections and optic radiations were studied as "control" WM
      tracts. The contribution of global brain damage (T2 lesion volume, normalized
      brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal
      appearing WM and GM damage) and damage to selected WM tracts to overall cognitive
      impairment and to impairment at individual neuropsychological tests was assessed
      using a random forest (RF) analysis. RESULTS: Thirty-three patients had cognitive
      impairment. The majority of MRI measures differed significantly between
      cognitively impaired and cognitively preserved (CP) patients. Significant
      correlations were found between performance in the majority of neuropsychological
      tests and global or regional brain damage (r ranging from -0.60 to 0.57). The RF
      analysis showed a high performance in classifying cognitively impaired vs CP
      patients, with a classification (C)-index = 76.8, as well as in classifying
      patients' impairment in individual neuropsychological tests (C-index between
      75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather
      than measures of normal-appearing WM damage in the same tracts or global
      brain/WM/GM damage, resulted in the highest classification accuracy. CONCLUSIONS:
      Lesions in strategic brain WM tracts contribute to cognitive impairment in MS
      through a multisystem disconnection syndrome.

PMID- 22377807
TI  - Increased risk of stroke after spinal cord injury: a nationwide 4-year follow-up
      cohort study.
AB  - OBJECTIVE: Spinal cord injury (SCI) is associated with a higher risk of
      cardiovascular diseases but whether or not the risk of cerebrovascular disease
      also increases remains unclear. This study aimed to evaluate the incidence of
      stroke in patients with disability caused by SCI. METHODS: Study subjects were
      identified from a nationwide cohort of 18,690,066 people from 1998 to 2002 that
      was divided into an SCI group (n = 2,806), who were disabled from SCI, and a
      comparison group (n = 28,060), composed of age-, sex-, and propensity score-
      matched control subjects. Every subject was followed up for 4 years, unless they
      died or had a stroke by December 31, 2006. Kaplan-Meier and Cox regression
      analyses were performed. RESULTS: The incidence rate of stroke in the SCI group
      (5.96 per 1,000 person-years) was higher than that of the comparison group (p <
      0.001). Stroke was more likely to occur in the SCI group than in the comparison
      group (crude hazard ratio 2.93, p < 0.001; adjusted hazard ratio 2.85, p <
      0.001). In the SCI group, the incidence of ischemic stroke was higher than that
      of hemorrhagic stroke (incidence rate ratio 3.42, p < 0.001). CONCLUSIONS: SCI
      patients with disability are at a higher risk of stroke, especially the ischemic
      type. Strategies to prevent stroke are therefore suggested for them.

PMID- 22377808
TI  - Combination therapy for chronic migraine: bad news but not the last word.

PMID- 22377809
TI  - The tremor network targeted by successful VIM deep brain stimulation in humans.
AB  - OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of
      thalamus (VIM) is a treatment option in medically intractable tremor, such as
      essential tremor or tremor-dominant Parkinson disease (PD). Although functional
      studies demonstrated modulation of remote regions, the structural network
      supporting this is as yet unknown. In this observational study, we analyzed the
      network mediating clinical tremor modulation. METHODS: We studied 12 patients
      undergoing VIM stimulation for debilitating tremor. We initiated noninvasive
      diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover,
      we tested for the contribution of primary motor projections in this structural
      correlate of a functional tremor network, comparing the connectivity of effective
      DBS contacts with those of adjacent, but clinically ineffective, stimulation
      sites. RESULTS: VIM stimulation resulted in decrease of tremor and improvement in
      quality of life. Tractography initiated from the effective stimulation site
      reconstructed a highly reproducible network of structural connectivity comprising
      motor cortical, subcortical, and cerebellar sites and the brainstem, forming the
      anatomic basis for remote effects of VIM stimulation. This network is congruent
      with functional imaging studies in humans and with thalamic projections found in
      the animal literature. Connectivity to the primary motor cortex seemed to play a
      key role in successful stimulation. CONCLUSIONS: Patients undergoing DBS provide
      a unique opportunity to assess an electrophysiologically defined seed region in
      human thalamus, a technique that is usually restricted to animal research. In the
      future, preoperative tractography could aid with stereotactic planning of
      individual subcortical target points for stimulation in tremor and in other
      disease entities.

PMID- 22377810
TI  - Relationship between etiology and covert cognition in the minimally conscious
      state.
AB  - OBJECTIVES: Functional neuroimaging has shown that the absence of externally
      observable signs of consciousness and cognition in severely brain-injured
      patients does not necessarily indicate the true absence of such abilities.
      However, relative to traumatic brain injury, nontraumatic injury is known to be
      associated with a reduced likelihood of regaining overtly measurable levels of
      consciousness. We investigated the relationships between etiology and both overt
      and covert cognitive abilities in a group of patients in the minimally conscious
      state (MCS). METHODS: Twenty-three MCS patients (15 traumatic and 8 nontraumatic)
      completed a motor imagery EEG task in which they were required to imagine
      movements of their right-hand and toes to command. When successfully performed,
      these imagined movements appear as distinct sensorimotor modulations, which can
      be used to determine the presence of reliable command-following. The utility of
      this task has been demonstrated previously in a group of vegetative state
      patients. RESULTS: Consistent and robust responses to command were observed in
      the EEG of 22% of the MCS patients (5 of 23). Etiology had a significant impact
      on the ability to successfully complete this task, with 33% of traumatic patients
      (5 of 15) returning positive EEG outcomes compared with none of the nontraumatic
      patients (0 of 8). CONCLUSIONS: The overt behavioral signs of awareness (measured
      with the Coma Recovery Scale-Revised) exhibited by nontraumatic MCS patients
      appear to be an accurate reflection of their covert cognitive abilities. In
      contrast, one-third of a group of traumatically injured patients in the MCS
      possess a range of high-level cognitive faculties that are not evident from their
      overt behavior.

PMID- 22377811
TI  - Predictors of hemorrhage volume and disability after perimesencephalic
      subarachnoid hemorrhage.
AB  - OBJECTIVE: The determinants of subarachnoid hemorrhage (SAH) volume and an
      atypical pattern of blood are not clear. Our objective was to determine if
      reduced platelet activity on admission and abnormal venous drainage are
      associated with greater SAH volume. METHODS: We prospectively identified
      noncomatose patients with SAH without an identifiable aneurysm. We routinely
      measured platelet activity on admission and recorded aspirin use. SAH volumes
      were calculated with a validated technique. CT angiograms were reviewed by a
      certified neuroradiologist for venous drainage. Patients were followed for
      clinical outcomes through 3 months with the modified Rankin Scale (mRS). Data are
      Q1-Q3. RESULTS: There were 31 patients in the cohort. Thirty (97%) underwent an
      angiogram on admission, and 25 (81%) an additional delayed angiogram. SAH volume
      was lowest with normal venous drainage bilaterally (4.4 [3.7-16.4] mL) and higher
      with 1 (12.9 [3.7-20.4]) or 2 (20.9 [12.5-34.6] mL, p = 0.03) discontinuous
      venous drainages. Patients with reduced platelet activity had more SAH on the
      diagnostic CT (17.5 [10.6-20.9] vs 6.1 [2.3-15.3] mL) (p = 0.046). SAH volume was
      greater for patients requiring drainage for hydrocephalus (16.4 [11.5-20.5] vs
      5.4 [2.7-16.4] mL) (p = 0.009). Outcomes at 3 months were generally excellent
      (median mRS = 0, no symptoms). CONCLUSIONS: Discontinuous venous drainage and
      reduced platelet activity were associated with increased SAH volume and
      hydrocephalus. These factors may explain thick SAH and reduce the need for
      repeated invasive imaging in such patients.

PMID- 22377812
TI  - Cerebrovascular pathology in cognitive impairment: new (in)sights.

PMID- 22377813
TI  - Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of
      moyamoya disease.
AB  - OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya
      disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype
      and MMD phenotype. METHODS: The entire coding region of the RNF213 gene was
      sequenced in 204 patients with MMD, and corresponding variants were checked in 62
      pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal
      controls. Clinical information was collected. Genotype-phenotype correlations
      were statistically analyzed. RESULTS: The c.14576G>A variant was identified in
      95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and
      1.8% of controls, thus confirming its association with MMD, with an odds ratio of
      259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A
      was observed in 15 patients but not in the controls and unaffected parents. The
      incidence rate for homozygotes was calculated to be >78%. Homozygotes had a
      significantly earlier age at onset compared with heterozygotes or wild types
      (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were
      diagnosed with MMD before age 4, and all had infarctions as the first symptom.
      Infarctions at initial presentation and involvement of posterior cerebral
      arteries, both known as poor prognostic factors for MMD, were of significantly
      higher frequency in homozygotes than in heterozygotes and wild types. Variants
      other than c.14576G>A were not associated with clinical phenotypes. CONCLUSIONS:
      The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for
      predicting the severe type of MMD, for which early medical/surgical intervention
      is recommended, and may provide a better monitoring and prevention strategy.

PMID- 22377814
TI  - Staging and natural history of cerebrovascular pathology in dementia.
AB  - OBJECTIVE: Most pathologic studies indicate that significant vascular changes are
      found in the majority of elderly persons, either alone or in association with
      neurodegenerative processes such as Alzheimer disease (AD) or dementia with Lewy
      bodies (DLB). Cumulative burden of cerebrovascular lesions can explain cognitive
      decline described as vascular cognitive impairment, but because there is a lack
      of consensus in the best way to quantify vascular pathology, the relationship
      between cognitive decline and cerebrovascular disease remains uncertain. We
      developed a rating scheme for cerebrovascular lesions using postmortem brains
      from patients with dementia from 2 European tertiary care memory clinics.
      METHODS: A total of 135 brains with a neuropathologic diagnosis of vascular
      dementia (VaD) (n = 26), AD + VaD (n = 39), DLB + VaD (n = 21), AD + DLB + VaD (n
      = 9), AD (n = 19), and DLB (n = 21) were investigated in this study.
      Cerebrovascular lesions were rated on large sections from the hippocampus, the
      temporal lobe, the frontal lobe, and basal ganglia. RESULTS: In patients with
      dementia, vessel wall modifications such as arteriolosclerosis or amyloid
      angiopathy are the most common and presumably the earliest changes. Modifications
      in perivascular spaces and myelin loss are the next most common. Lacunar or
      regional infarcts may occur as a consequence of an independent process or in the
      final phase of small vessel diseases. CONCLUSION: A staging system based on this
      conceptual model of cerebrovascular pathology could enable the neuropathologic
      quantification of the cerebrovascular burden in dementia. Further studies are
      needed to determine whether this system can be used in large-scale studies to
      understand clinical-cerebrovascular pathologic correlations.

PMID- 22377816
TI  - Is spinal cord injury a new emerging risk factor for stroke?

PMID- 22377817
TI  - Peripheral nerve inflammation in ALS mice: cause or consequence.

PMID- 22377818
TI  - Immune response against Streptococcus gallolyticus in patients with adenomatous
      polyps in colon.
AB  - Our aim was to examine the humoral immune response against Streptococcus
      gallolyticus subspecies gallolyticus antigens in individuals subjected to a
      routine colonoscopy in which colon adenomatous polyps were present or not. Serum
      samples from 133 individuals with adenomatous polyps and serum samples from 53
      individuals with a normal colonoscopy were included. Western blot was performed
      in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and
      rabbit antisera against the whole cell bacteria was prepared as a control. By
      analyzing the immune profile of the rabbit-immunized sera by Western-blot, at
      least 22 proteins were identified as immunogenic in S. gallolyticus. When we
      evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa
      were most prominent. Based on this 2-protein band pattern, Western-blot profiles
      from human subjects were compared. The detection of a protein band of 22 kDa was
      associated with the presence of adenomatous polyps in colon [odds ratios (OR)
      7.98, 95% confidence intervals (CI): 3.54-17.93], p < 0.001. When the presence of
      the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR
      increased to 22.37 (95% CI: 3.77-131.64), p < 0.001. The specificity was 84.9 for
      the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa
      protein alone or both 22 and 30 kDa bands. Serum from individuals with
      adenomatous polyps recognized two proteins from S. gallolyticus. This result
      confirmed the possible association of S. gallolyticus with adenomatous polyps in
      the colon.

PMID- 22377815
TI  - Randomized, placebo-controlled trial of propranolol added to topiramate in
      chronic migraine.
AB  - OBJECTIVE: To assess the efficacy and safety of adding propranolol to topiramate
      in chronic migraine subjects inadequately controlled with topiramate alone.
      METHODS: This was a double-blind, placebo-controlled, randomized clinical trial
      conducted through the National Institute of Neurological Disorders and Stroke
      Clinical Research Collaboration, expected to randomize 250 chronic migraine
      subjects inadequately controlled (>=10 headaches/month) with topiramate (50-100
      mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary
      outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks
      16 to 24) compared with baseline (weeks -4 to 0). RESULTS: A planned interim
      analysis was performed after 48 sites randomized 171 subjects. The data and
      safety monitoring board recommended ending the trial after determining that it
      would be highly unlikely for the combination to result in a significant reduction
      in 28-day headache rate compared with topiramate alone if all 250 subjects were
      randomized. No safety concerns were identified. At study closure, 191 subjects
      were randomized. The 6-month reduction in moderate to severe 28-day headache rate
      and total 28-day headache rate for combination therapy vs topiramate alone was
      not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache
      rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91).
      CONCLUSIONS: This study does not provide evidence that the addition of
      propranolol LA to topiramate adds benefit when chronic migraine is inadequately
      controlled with topiramate alone. CLASSIFICATION OF EVIDENCE: This study provides
      Class II evidence that propranolol LA, added to topiramate, is ineffective in
      chronic migraine patients who fail topiramate monotherapy.

PMID- 22377819
TI  - Effect of neoadjuvant chemotherapy in hepatic steatosis.
AB  - Chemotherapy drugs often produce side effects in the liver. In recent years,
      there has been speculation about the ability to produce hepatic steatosis in
      patients treated with 5-fluorouracil and oxaliplatin. This prospective study
      examines whether these drugs can produce steatosis in patients with neoadjuvant
      treatment who were operated on for liver tumors. PURPOSE: Our objective was to
      assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic
      steatosis in the healthy liver. PATIENTS AND METHODS: This was a prospective
      study based on 32 patients divided into two groups. The presence of steatosis was
      assessed using a histological score (Kleiner classification) and a biochemical
      method (Folch method) for patients from both groups. RESULTS: A total of 14
      patients (44%) had hepatic steatosis and half of these were in each group. The
      steatosis was moderate to severe (grades 2-3) in 4 patients (13%), 2 in each
      group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in
      group I and group II, respectively, with the difference not being statistically
      significant. CONCLUSIONS: Almost half of the patients treated with NAC for liver
      neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the
      risk of hepatic steatosis.

PMID- 22377820
TI  - Early enteral nutrition reduces the rate of life-threatening complications after
      thoracic esophagectomy in patients with esophageal cancer.
AB  - BACKGROUND: Early postoperative enteral nutrition has been suggested to improve
      the nutritional status of patients after esophageal surgery. However, whether
      enteral nutrition decreases rates of surgical complications and increases the
      completion rate of the clinical management pathway is unclear. METHODS: We
      analyzed 154 patients who were randomly assigned to either an enteral or
      parenteral nutrition group after undergoing esophagectomy, compared the incidence
      of surgical complications, and evaluated the completion rate of the clinical
      pathway. In these 2 patient groups, perioperative management was performed
      through identical clinical pathways, except for nutrition. RESULTS: The overall
      rate of surgical complications of any type did not differ between patients who
      received early enteral nutrition and those who did not (p = 0.50); however, the
      rate of life-threatening surgical complications was significantly lower in
      patients who received early enteral nutrition (p = 0.02). The rate of non-life
      threatening surgical complications did not differ between the groups (p = 0.98).
      In patients who received enteral nutrition, the completion rate of the clinical
      pathway was higher (p = 0.03), and the postoperative hospital stay was shorter (p
      = 0.04). CONCLUSIONS: Early enteral nutrition reduces the incidence of life
      threatening surgical complications and improves the completion rate of the
      clinical pathway for thoracic esophagectomy.

PMID- 22377823
TI  - Impact of a required fourth-year medical student rotation in physical medicine
      and rehabilitation.
AB  - This study evaluated the impact of a 2-wk required rotation in Physical Medicine
      and Rehabilitation (PM&R) on fourth-year medical students' knowledge of PM&R and
      attitude toward teamwork in patient care. Survey results on attitudes toward a
      team approach to patient care and knowledge in PM&R were compared prerotation and
      postrotation. One hundred thirty-eight fourth-year medical students participated
      in this 2-yr study. The combined response rates for the attitude and knowledge
      surveys were 62% and 56%, respectively. As measured by a pretest and posttest
      self-reported knowledge assessment, the rotation increased knowledge of PM&R (P
      <= 0.05). Four aspects of the rotation that were rated higher by students from
      the second year of the rotation were role and responsibility definition,
      incorporation of current literature, enhancement of clinical skills, and general
      rotation satisfaction. The rotation provides an experience for medical students
      to increase their knowledge of PM&R.

PMID- 22377824
TI  - Measuring treatment fidelity in a rehabilitation intervention study.
AB  - Attaining and demonstrating treatment fidelity is critical in the development and
      testing of evidence-based interventions. Treatment fidelity refers to the extent
      to which an intervention was implemented in clinical testing as it was
      conceptualized and is clearly differentiable from control or standard-of-care
      interventions. In clinical research, treatment fidelity is typically attained
      through intensive training and supervision techniques and demonstrated by
      measuring therapist adherence and competence to the protocol using external
      raters. However, in occupational and physical therapy outcomes research,
      treatment fidelity methods have not been used, which, in our view, is a serious
      gap that impedes novel treatment development and testing in these rehabilitation
      fields. In this article, we describe the development of methods to train and
      supervise therapists to attain adequate treatment fidelity in a treatment
      development project involving a novel occupational and physical therapy-based
      intervention. We also present a data-driven model for demonstrating therapist
      adherence and competence in the new treatment and its differentiation from
      standard of care. In doing so, we provide an approach that rehabilitation
      researchers can use to address treatment fidelity in occupational and physical
      therapy-based interventions. We recommend that all treatment researchers in
      rehabilitation disciplines use these or similar methods as a vital step in the
      development and testing of evidence-based rehabilitation interventions.

PMID- 22377825
TI  - Tension pneumocephalus as a complication of hyperbaric oxygen therapy in a
      patient with chronic traumatic brain injury.
AB  - Although hyperbaric oxygen therapy has not been accepted as a standard therapy
      for traumatic brain injuries, it has been used, along with rehabilitative
      exercises, for traumatic brain injuries, and the standard protocol has a low risk
      of complications. We report a case of chronic traumatic brain injury that
      progressed to tension pneumocephalus after hyperbaric oxygen therapy. The patient
      was a 25-yr-old man who presented with left occipital bone fracture and
      subarachnoid and subdural hemorrhage after being hit by a car. He underwent
      craniectomy to remove the hematoma and cerebrospinal fluid diversion with a
      ventriculoperitoneal shunt for the treatment of hydrocephalus. Fifteen months
      after the trauma, the patient received hyperbaric oxygen therapy to promote
      functional recovery. Tension pneumocephalus developed after the first session of
      hyperbaric oxygen therapy, and immediate burr hole drainage followed by ligation
      of the ventriculoperitoneal shunt was performed. The patient's consciousness
      recovered gradually, and he was discharged home. We suggest that patients with
      unrepaired skull base fracture and cerebrospinal fluid diversion should be
      carefully evaluated before receiving hyperbaric oxygen therapy.

PMID- 22377826
TI  - Ganglion cyst of radiocapitellar joint mimicking lateral epicondylitis: role of
      ultrasonography.

PMID- 22377827
TI  - Development of the participation scale for patients with congestive heart
      failure.
AB  - OBJECTIVE: We report on the development of a participation measure for patients
      with congestive heart failure (CHF)-the Participation Scale for Patients with CHF
      (PS-CHF)-and the determination of its unidimensionality, reliability, and
      validity. DESIGN: This study included two rounds of data collections: 62 patients
      enrolled in the first round for the purpose of item reduction, and 130 CHF
      patients and 96 healthy controls participated in the second round for
      questionnaire validation. RESULTS: The PS-CHF was organized into five items
      designed to ask about limitations to participation. The PS-CHF score ranges from
      5 points (lowest level of participation) to 20 points (highest level of
      participation). On Rasch analysis, the item calibrations ranged from +0.51 logit
      for the most difficult item to -0.56 logit for the least difficult item. The
      range of mean square statistics values was 1.20-0.81 for infit and 1.34-0.72 for
      outfit. The intraclass correlation coefficient between scores from two successive
      administrations of the PS-CHF, separated by 2 wks, was 0.94. The total PS-CHF
      score in CHF patients was significantly lower than in healthy controls.
      CONCLUSIONS: The PS-CHF was developed to determine a disease-specific
      participation measure for patients with CHF. The PS-CHF may serve as a clinically
      meaningful outcome measure for CHF patients.

PMID- 22377829
TI  - Alcohol and kidney damage: a Janus-faced relationship.
AB  - It has been known for a long time that excessive consumption of alcohol has
      adverse effects, including adverse impact on kidneys and kidney disease.
      Recently, observational evidence has been provided that moderate alcohol
      consumption is associated with less cardiovascular and renal risk. These issues
      had been summarized and discussed at the recent congress of the European Society
      for Biomedical Research and Alcoholism in Vienna.

PMID- 22377831
TI  - Hiccups: a new explanation for the mysterious reflex.
AB  - The hiccup may have evolved to remove swallowed air from the stomach, which may
      help suckling mammals to consume more milk.

PMID- 22377830
TI  - Deletion of scavenger receptor A protects mice from progressive nephropathy
      independent of lipid control during diet-induced hyperlipidemia.
AB  - Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of
      lipids and contributes to the pathogenesis of atherosclerosis. To assess its role
      in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout)
      mice underwent uninephrectomy followed by either normal or high-fat diet. After
      16 weeks of diet intervention, hyperlipidemic wild-type mice presented
      characteristic features of progressive nephropathy: albuminuria, renal fibrosis,
      and overexpression of transforming growth factor (TGF)-beta1/Smad. These changes
      were markedly diminished in hyperlipidemic knockout mice and attributed to
      reduced renal lipid retention, oxidative stress, and CD11c(+) cell infiltration.
      In vitro, overexpression of SR-A augmented monocyte chemoattractant protein-1
      release and TGF-beta1/Smad activation in HK-2 cells exposed to oxidized low
      density lipoprotein. SR-A knockdown prevented lipid-induced cell injury.
      Moreover, wild-type to knockout bone marrow transplantation resulted in renal
      fibrosis in uninephrectomized mice following 16 weeks of the high-fat diet. In
      contrast, knockout to wild-type bone marrow transplantation led to markedly
      reduced albuminuria, CD11c(+) cell infiltration, and renal fibrosis compared to
      wild-type to SR-A knockout or wild-type to wild-type bone marrow transplanted
      mice, without difference in plasma lipid levels. Thus, SR-A on circulating
      leukocytes rather than resident renal cells predominantly mediates lipid-induced
      kidney injury.

PMID- 22377832
TI  - C-C, C-O and C-N bond formation via rhodium(III)-catalyzed oxidative C-H
      activation.
AB  - Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative
      conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene
      substrates bearing nitrogen and oxygen directing groups are covered in their
      coupling with unsaturated partners such as alkenes and alkynes. The facile
      construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an
      attractive step-economic approach to value-added molecules from readily available
      starting materials. Comparisons and contrasts between rhodium(III) and
      palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of
      structures accessible is demonstrated with various recent examples, with a
      proposed mechanism for each transformation being briefly summarized (critical
      review, 138 references).

PMID- 22377833
TI  - Modulating neuronal excitability in the motor cortex with tDCS shows moderate
      hemispheric asymmetry due to subjects' handedness: a pilot study.
AB  - PURPOSE: Transcranial direct current stimulation (tDCS) has proven to be a useful
      tool for fundamental brain research as well as for attempts in therapy of
      neurological and psychiatric diseases by modulating neuronal plasticity. Little
      is understood about the effects of tDCS are influenced by hemispheric dominance,
      even less in terms of handedness. The aim of our pilot study was to investigate
      whether tDCS induced neuroplastic changes may be different in right- and left
      handed individuals due to existing differences in hemispheric lateralisation.
      METHODS: We measured changes in motor evoked potentials (MEPs) after application
      of tDCS in 8 right-handers, 8 left-handers and 8 mixed-handers according to the
      Edinburgh Handedness Inventory (EHI). In double-blind sessions, we applied either
      anodal or cathodal tDCS for 5 minutes for each hemisphere. RESULTS: While motor
      thresholds (MT) seem to be not influenced by handedness significantly, in right
      handed subjects we reproduced the well-known effects of tDCS: anodal stimulation
      increased while cathodal stimulation decreased MEP amplitudes. However, left-and
      mixed-handed subjects differed from right-handed subjects. After anodal
      stimulation of the left hemisphere the increase of the MEP amplitudes was
      stronger in right handed subjects than in left and mixed handed subjects.
      Interestingly, after cathodal stimulation of the left hemisphere this difference
      was less marked. The stimulation of the right hemisphere showed the same
      tendency, but results were not significant. CONCLUSIONS: For the first time, we
      are able to demonstrate that the modulating effects of tDCS on corticospinal
      excitability differ moderately in the left-and mixed-handed population compared
      to right-handed subjects. The shown differences according to handedness should be
      taken into account in further studies.

PMID- 22377834
TI  - Do participants' preferences for mode of delivery (text, video, or both)
      influence the effectiveness of a Web-based physical activity intervention?
AB  - BACKGROUND: In randomized controlled trials, participants cannot choose their
      preferred intervention delivery mode and thus might refuse to participate or not
      engage fully if assigned to a nonpreferred group. This might underestimate the
      true effectiveness of behavior-change interventions. OBJECTIVE: To examine
      whether receiving interventions either matched or mismatched with participants'
      preferred delivery mode would influence effectiveness of a Web-based physical
      activity intervention. METHODS: Adults (n = 863), recruited via email, were
      randomly assigned to one of three intervention delivery modes (text based, video
      based, or combined) and received fully automated, Internet-delivered personal
      advice about physical activity. Personalized intervention content, based on the
      theory of planned behavior and stages of change concept, was identical across
      groups. Online, self-assessed questionnaires measuring physical activity were
      completed at baseline, 1 week, and 1 month. Physical activity advice
      acceptability and website usability were assessed at 1 week. Before
      randomization, participants were asked which delivery mode they preferred, to
      categorize them as matched or mismatched. Time spent on the website was measured
      throughout the intervention. We applied intention-to-treat, repeated-measures
      analyses of covariance to assess group differences. RESULTS: Attrition was high
      (575/863, 66.6%), though equal between groups (t(86) (3) =1.31, P =.19). At 1
      month follow-up, 93 participants were categorized as matched and 195 as
      mismatched. They preferred text mode (493/803, 61.4%) over combined (216/803,
      26.9%) and video modes (94/803, 11.7%). After the intervention, 20% (26/132) of
      matched-group participants and 34% (96/282) in the mismatched group changed their
      delivery mode preference. Time effects were significant for all physical activity
      outcomes (total physical activity: F(2,801) = 5.07, P = .009; number of activity
      sessions: F(2,801) = 7.52, P < .001; walking: F(2,801) = 8.32, P < .001; moderate
      physical activity: F(2,801) = 9.53, P < .001; and vigorous physical activity:
      F(2,801) = 6.04, P = .002), indicating that physical activity increased over time
      for both matched and mismatched groups. Matched-group participants improved
      physical activity outcomes slightly more than those in the mismatched group, but
      interaction effects were not significant. Physical activity advice acceptability
      (content scale: t(368) = .10, P = .92; layout scale: t(368) = 1.53, P = .12) and
      website usability (layout scale: t(426) = .05, P = .96; ease of use scale: t(426)
      = .21, P = .83) were generally high and did not differ between the matched and
      mismatched groups. The only significant difference (t(621) = 2.16, P = .03) was
      in relation to total time spent on the website: the mismatched group spent
      significantly more time on the website (14.4 minutes) than the matched group
      (12.1 minutes). CONCLUSION: Participants' preference regarding delivery mode may
      not significantly influence intervention outcomes. Consequently, allowing
      participants to choose their preferred delivery mode may not increase
      effectiveness of Web-based interventions.

PMID- 22377835
TI  - Low diastolic blood pressure is associated with the progression of normal-tension
      glaucoma.
AB  - AIMS: The objective of this study was to investigate the association between
      blood pressure (BP) and visual field defect progression in normal-tension
      glaucoma (NTG). METHODS: The subjects were 35 consecutive patients with NTG who
      were admitted to Keio University Hospital for 24-hour intraocular pressure
      evaluation; all subjects underwent 6 or more visual field tests in either eye and
      were followed up for more than 5 years. Systolic and diastolic BPs were measured
      at 9.00 h. Subjects with negative regression lines and p values of less than 0.05
      were classified as progressive; all others were defined as stable. Systolic BP,
      diastolic BP, and ocular perfusion pressure were compared between the 2 groups.
      RESULTS: Twelve subjects showed progression in glaucomatous visual field defects
      (age 55.1 +/- 15.1 years). Twenty-three subjects showed no progression (age 57.2
      +/- 10.9 years). Diastolic BP (stable group: 77.0 +/- 12.1 mm Hg; progressive
      group: 67.7 +/- 9.7 mm Hg; p = 0.03) was significantly lower in the progressive
      group than in the stable group. Multivariable analysis revealed that low
      diastolic BP is a significant risk factor for progression (OR 0.90; 95% CI 0.82
      0.99). CONCLUSIONS: Low diastolic BP was associated with glaucomatous visual
      field progression in subjects with NTG.

PMID- 22377836
TI  - Is barefoot running more economical?

PMID- 22377838
TI  - Psychogenic skin excoriations: diagnostic criteria, semiological analysis and
      psychiatric profiles.
AB  - Psychogenic excoriations are also called neurotic excoriations, dermatillomania
      or skin picking syndrome. We proposed diagnostic criteria and then performed a
      study of the psychiatric profiles of outpatients with psychogenic excoriations
      and the circumstances around the creation of these excoriations. Although the
      results must be interpreted with caution because the study was performed with
      only 10 patients, interesting data is provided about the onset of psychogenic
      excoriations, the behaviour of picking, and comorbidity. Common or specific
      characteristics were identified according to type of case. The majority of
      patients associated first excoriations with personal problems. Four patients
      reported abuse in childhood or adolescence. This study confirms that skin picking
      is an impulsive reaction and does not belong to the obsessive-compulsive
      disorders: impulsivity is defined by ineffective or failing control resulting in
      uninhibited behaviour.

PMID- 22377839
TI  - Statistics-based model for basis set superposition error correction in large
      biomolecules.
AB  - We describe a statistics-based model for the estimation of basis set
      superposition error (BSSE) for large biomolecular systems in which molecular
      fragment interactions are classified and analyzed with a linear model based on a
      bimolecular proximity descriptor. The models are trained independently for
      different classes of molecular interactions, quantum methods, and basis sets. The
      predicted fragment BSSE values, along with predicted uncertainties, are then
      propagated throughout the supermolecule to yield an overall estimate of BSSE and
      associated uncertainty. The method is described and demonstrated at the MP2/6
      31G* and MP2/aug-cc-pVDZ levels of theory on a protein-ligand complex, a small
      helical protein, and a set of native and decoy folds of the Pin1 WW domain.

PMID- 22377840
TI  - Value of high frequency ultrasonography in diagnosis and surgical repair of
      traumatic finger tendon ruptures.
AB  - OBJECTIVE: To investigate the value of high frequency ultrasonography in the
      diagnosis of zone 2 flexor tendon injuries. SUBJECTS AND METHODS: Ninety-two
      patients (49 males and 43 females, mean age 32.6 +/- 11.2 years) with zone 2
      flexor tendon injuries in one or more digits were randomly divided into a study
      (n = 46, 95 digits) and a control group (n = 46, 90 digits). In the study group,
      preoperative ultrasound was performed and surgical repair was conducted based on
      ultrasonographic findings. Diagnosis and surgical repair of the control group was
      based on history of trauma and physical examination. RESULTS: Types of ruptures
      (complete or partial) and the location of the distal end of the ruptured tendon
      diagnosed by preoperative ultrasonography were consistent with surgical findings
      in all cases (95/95, 100%) of the study group, whereas the concordance rate
      between clinically diagnosed ruptures and surgical findings was only 34.4%
      (31/90) in the control group (p = 0.02). CONCLUSION: Preoperative high frequency
      ultrasound examination yielded excellent diagnostic accuracy for zone 2 flexor
      tendon injuries.

PMID- 22377841
TI  - Carotid artery disease in Sub-Saharan Africa: a marker of epidemiological and
      stroke transition.

PMID- 22377842
TI  - The arterialized saphenous venous flow-through flap with dual venous drainage.
AB  - BACKGROUND: Venous flow-through flaps are well-described options for small
      defects where donor site morbidity is undesirable or in areas where useful local
      veins are in close proximity to the defect, particularly in the extremities.
      However, higher rates of flap loss have limited their utility. The saphenous
      venous flap in particular has been widely sought as a useful flap, and while
      arterialization of this flap improved survival rates, congestion has remained a
      limiting feature. We describe report a modification in the design of saphenous
      venous flaps, whereby an arterialized flap is provided with a separate source of
      venous drainage, and demonstrate survival of substantially larger venous flaps
      than previously reported. METHODS: In five consecutive patients, we describe
      three main modifications to the saphenous venous flap as previously described:
      (a) Using arterialized flaps only; (b) Reversing the flap to allow unimpeded flow
      during arterialization; and (c) Anastomosing additional vein(s) that are not
      connected to the central vein-especially at the periphery of the flap for true
      venous drainage. RESULTS: There was a 0% complete flap loss rate (with only one
      case of superficial partial loss), and ultimately better survival than previous
      series of saphenous venous flaps described to date. CONCLUSION: The success of
      these techniques offers the potential to re-establish flow to large segmental
      losses to axial arteries, offer safe and definitive flap coverage to traumatic
      wounds, improve the array of flap options in this setting, and minimize donor
      site morbidity.

PMID- 22377843
TI  - HIV infection and HIV-associated behaviors among injecting drug users - 20
      cities, United States, 2009.
AB  - Despite a recent reduction in the number of human immunodeficiency virus (HIV)
      infections attributed to injecting drug use in the United States, 9% of new U.S.
      HIV infections in 2009 occurred among injecting drug users (IDUs). To monitor HIV
      associated behaviors and HIV prevalence among IDUs, CDC's National HIV Behavioral
      Surveillance System (NHBS) conducts interviews and HIV testing in selected
      metropolitan statistical areas (MSAs). This report summarizes data from 10,073
      IDUs interviewed and tested in 20 MSAs in 2009. Of IDUs tested, 9% had a positive
      HIV test result, and 45% of those testing positive were unaware of their
      infection. Among the 9,565 IDUs with HIV negative or unknown HIV status before
      the survey, 69% reported having unprotected vaginal sex, 34% reported sharing
      syringes, and 23% reported having unprotected heterosexual anal sex during the 12
      previous months. Although these risk behavior prevalences appear to warrant
      increased access to HIV testing and prevention services, for the previous 12
      month period, only 49% of the IDUs at risk for acquiring HIV infection reported
      having been tested for HIV, and 19% reported participating in a behavioral
      intervention. Increased HIV prevention and testing efforts are needed to further
      reduce HIV infections among IDUs.

PMID- 22377844
TI  - Exposure to nitrogen dioxide in an indoor ice arena - New Hampshire, 2011.
AB  - In January 2011, the New Hampshire Department of Health and Human Services
      (NHDHHS) investigated acute respiratory symptoms in a group of ice hockey
      players. The symptoms, which included cough, shortness of breath, hemoptysis, and
      chest pain or tightness, were consistent with exposure to nitrogen dioxide gas
      (NO), a byproduct of combustion. Environmental and epidemiologic investigations
      were begun to determine the source of the exposure and identify potentially
      exposed persons. This report summarizes the results of those investigations,
      which implicated a local indoor ice arena that had hosted two hockey practice
      sessions during a 24-hour period when the arena ventilation system was not
      functioning. A total of 43 exposed persons were interviewed, of whom 31 (72.1%)
      reported symptoms consistent with NO exposure. The highest attack rate was among
      the hockey players (87.9%). After repair of the ventilation system, no additional
      cases were identified. To prevent similar episodes, ice arena operators should
      ensure ventilation systems and alarms are operating properly and that levels of
      NO and carbon monoxide (CO) are monitored continuously for early detection of
      increased gas levels.

PMID- 22377845
TI  - Chronic obstructive pulmonary disease and associated health-care resource use -
      North Carolina, 2007 and 2009.
AB  - Chronic obstructive pulmonary disease (COPD), including emphysema and chronic
      bronchitis, is a progressive condition in which airflow becomes limited, making
      it difficult to breathe. Chronic lower respiratory diseases, primarily COPD, are
      the third leading cause of death in the United States, and 5.1% of U.S. adults
      report a diagnosis of emphysema or chronic bronchitis. Smoking is the primary
      cause of COPD, and at least 75% of COPD deaths are attributable to smoking in the
      United States. Information on state-specific prevalence of COPD is sparse, as are
      data on the use of COPD-related health-care resources. To understand how COPD
      affects adults in North Carolina and what resources are used by persons with
      COPD, 2007 and 2009 data from the North Carolina COPD module of the Behavioral
      Risk Factor Surveillance System (BRFSS) were analyzed. Among 26,227 respondents,
      5.7% reported ever having been told by a health professional that they had COPD.
      Most adults with COPD reported ever having had a diagnostic breathing test (76.4%
      in 2007 and 82.4% in 2009). Among adults with COPD, 43.0% reported having gone to
      a physician and 14.9% visited an emergency department (ED) or were admitted to a
      hospital (2007) for COPD-related symptoms in the previous 12 months. Only 48.1%
      of persons reported daily use of medications for their COPD (2007). These results
      indicate that many adults with COPD might not have had adequate diagnostic
      spirometry, and many who might benefit from daily medications, such as long
      acting bronchodilators and inhaled corticosteroids, are not taking them.
      Continued and expanded surveillance is needed to evaluate the effectiveness of
      prevention and intervention programs and support efforts to educate the public
      and physicians about COPD symptoms, diagnosis, and treatment.

PMID- 22377846
TI  - Tailoring neoadjuvant chemotherapy for locally advanced breast cancer: a
      historical prospective study.
AB  - BACKGROUND: Despite the growing number of clinical trials assessing preoperative
      systemic chemotherapy (PST) for locally advanced breast cancer, the optimal
      regimen has still to be defined. PURPOSE: This was to evaluate the toxicity,
      operability rate, pathological response rate and disease-free and overall
      survival associated with a PST regimen consisting of the sequential
      administration of single agents according to the individual tumor response.
      METHODS: Medical files were reviewed of 102 consecutive patients with breast
      cancer treated in 2000-2007 with a neoadjuvant sequential regimen of doxorubicin
      followed by taxane. The number of cycles and the addition of taxane were based on
      tumor response. RESULTS: Seventy percent of the patients had inoperable disease
      at diagnosis and 29% were given preoperative therapy for breast conservation. All
      patients underwent surgery, 65% achieved breast conservation. An overall
      pathological complete response (breast and nodes) was achieved in 14% of the
      patients, and a complete nodal pathologic response in 34%. At a median follow-up
      of 54 months, the overall survival rate was 82% and the disease-free survival
      rate was 70%. There was no treatment-related mortality. Febrile neutropenia
      occurred in 19% of the patients. CONCLUSIONS: A neoadjuvant regimen of
      doxorubicin with or without a sequential taxane, in which the number of cycles
      and the sequential administration of taxane are determined according to clinical
      response, appears to be safe and effective for patients with locally advanced
      breast cancer and yields a high rate of breast conservation. Tailored PST can
      spare patients receiving unnecessary chemotherapy.

PMID- 22377847
TI  - Expression levels of microRNA-375 in colorectal carcinoma.
AB  - MicroRNAs are small, non-coding RNAs of endogenous origin. They have been
      increasingly shown to have altered expressions in many cancer types. The
      expression levels of miR-375 have not been comprehensively investigated in
      colorectal cancer. In this study, total RNA was extracted from 95 pairs of
      colorectal cancer tissues and non-tumor adjacent tissues, as well as from three
      colorectal cancer cell lines (HT-29, HCT-116 and SW-620). After polyadenylation
      and reverse transcription, we determined the expression levels of miR-375 by real
      time PCR and calculated the difference in expression using the 2-??Ct method. We
      assessed the correlation between the expression levels of miR-375 and
      clinicopathological characteristics of colorectal cancer. miR-375 expression was
      frequently downregulated in the colorectal cancer tissues compared to the non
      tumor counterparts (p<0.001; paired t-test). Moreover, a significantly low
      expression of miR-375 was also found in the colorectal cancer cell lines (HT-29,
      p=0.002; HCT-116, p<0.001; SW-620, p=0.004; paired t-test). However, there were
      no significant correlations between the low expression of miR-375 and tumor size,
      histological grade, pT stage, pN stage and pTNM stage (all P>0.05, non-parametric
      test; Mann-Whitney U test between two groups and Kruskal-Wallis H test for three
      or more groups). miR-375 may be involved in the carcinogenesis of colorectal
      cancers and may be a potential biomarker for colorectal cancers.

PMID- 22377848
TI  - The tooth fairy:  a cautionary tale.

PMID- 22377849
TI  - Under diagnosis of adult ADHD: cultural influences and societal burden.
AB  - OBJECTIVE: To explore the literature focusing on cultural influences in the
      diagnosis of adult ADHD and respective societal burden. METHOD: A review of the
      literature over the past 10 years was performed using OVID. RESULTS: Although
      numerous articles focused on diagnosis and burden of adult ADHD, few focused on
      cultural factors influencing diagnosis. Like other mental health disorders,
      cultural and social perspectives contribute to our understanding of adult ADHD
      and may play a significant role in the diagnosis and varying acceptance of the
      condition. Moreover, adults with ADHD may underestimate the impact of ADHD
      symptoms, and in many cases have learned to compensate for ADHD related
      impairments by choosing lifestyles that help compensate for symptoms. Some adults
      with ADHD may appear to function well, however they may expend excessive amounts
      of energy to overcome impairments; and they may be distressed by ongoing symptoms
      such as restlessness, mood instability and low self-esteem. Research shows that
      ADHD can be detrimental to many areas of life including work, daily activities,
      social and family relationships and psychological and physical well-being.
      Patient-reported impairments in productivity due to poor time management,
      procrastination, and distractibility can translate into significant indirect
      costs and decreased quality of life. ADHD in adults is also associated with
      increased accidents, medical resource utilization, antisocial behaviour and drug
      alcohol abuse. CONCLUSION: The substantial societal burden of adult ADHD
      highlights the importance of providing a better understanding of the factors that
      contribute to accurate diagnosis and of improving the low recognition of the
      disorder in many world regions.

PMID- 22377850
TI  - Motor syndromes.
AB  - Motor disturbances alone or associated with other focal deficits are the most
      common symptoms suggesting a neurovascular event. An appropriate clinical
      assessment of these signs and symptoms may help physicians to better diagnose and
      to both better treat and predict outcome. In this paper the main clinical
      features of motor deficit are described together with other motor-related events
      such as ataxia and movement disturbances.

PMID- 22377851
TI  - Sensory syndromes.
AB  - Somatosensory deficit syndromes represent a common impairment following stroke
      and have a prevalence rate of around 80% in stroke survivors. These deficits
      restrict the ability of survivors to explore and manipulate their environment and
      are generally associated with a negative impact on quality of life and personal
      safety. Sensory impairments affect different sensory modalities in diverse
      locations at varying degrees, ranging from complete hemianesthesia of multiple
      modalities to dissociated impairment of somatosensory submodalities within a
      particular region of the body. Sensory impairments induce typical syndromal
      patterns which can be differentiated by means of a careful neurological
      examination, allowing the investigator to deduce location and size of the
      underlying stroke. In particular, a stroke located in the brainstem, thalamus,
      and the corticoparietal cortex result in well-differentiable sensory syndromes.
      Sensory function following stroke can be regained during rehabilitation even
      without specific sensory training. However, there is emerging evidence that
      specialized sensory interventions can result in improvement of somatosensory and
      motor function. Herein, we summarize the clinical presentations, examination,
      differential diagnoses, and therapy of sensory syndromes in stroke.

PMID- 22377852
TI  - Headache.
AB  - Headache can be a symptom of vast pathologies, and common secondary headache
      including head or neck trauma, cranial or cervical vascular disorder, non
      vascular intracranial disorders headache related to a substance or its
      withdrawals, infection, disorders of homeostasis, disorders of cranium or facial
      mouth or cranial disorders, and headache attributable to psychiatric. Stroke
      related headache has been reported between 7 and 65% and headache is also the
      most frequent symptom of cerebral venous thrombosis, which is present in nearly
      90% of patients.

PMID- 22377853
TI  - Eye movement abnormalities.
AB  - Generation and control of eye movements requires the participation of the cortex,
      basal ganglia, cerebellum and brainstem. The signals of this complex neural
      network finally converge on the ocular motoneurons of the brainstem. Infarct or
      hemorrhage at any level of the oculomotor system (though more frequent in the
      brain-stem) may give rise to a broad spectrum of eye movement abnormalities
      (EMAs). Consequently, neurologists and particularly stroke neurologists are
      routinely confronted with EMAs, some of which may be overlooked in the acute
      stroke setting and others that, when recognized, may have a high localizing
      value. The most complex EMAs are due to midbrain stroke. Horizontal gaze
      disorders, some of them manifesting unusual patterns, may occur in pontine
      stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke.
      This review summarizes the most representative EMAs from the supratentorial level
      to the brainstem.

PMID- 22377854
TI  - Visual dysfunctions.
AB  - Damage at many different locations within the visual system can result in visual
      deficits, and a knowledge of the anatomy involved makes it possible to understand
      these deficits. In this chapter, we will review the visual system from basic
      anatomy to the description of more complex higher visual function.

PMID- 22377855
TI  - Dizziness and vertigo.
AB  - Dizziness is a general, non-specific term to indicate a sense of disorientation.
      Vertigo is a subtype of dizziness and refers to an erroneous perception of self-
      or object-motion or an unpleasant distortion of static gravitational orientation
      that is a result of a mismatch between vestibular, visual, and somatosensory
      systems. Vertigo is among the most common complaints in medicine, affecting
      approximately 20-30% of the general population. Stroke accounts for 3-7% among
      all causes of vertigo. The blood perfusion to the inner ear, brainstem, and
      cerebellum arise from the vertebrobasilar system. Vertigo, nausea, and vomiting,
      along with nystagmus, represent symptoms of stroke in posterior fossa due to
      arterial occlusion or rupture of the vertebrobasilar system. However, the
      spectrum of signs and symptoms as a manifestation of stroke associated with
      dizziness and vertigo may be variable depending on the affected vascular
      territories. Stroke or transient ischemic attack should be seriously considered
      in patients presenting with acute vertigo in the emergency room. Differential
      diagnosis between vascular vertigo and other causes of vertigo can result in
      misclassification due to the overlapping of symptoms. Careful medical history,
      physical examination, neuroimaging and ear, nose, and throat studies may help to
      distinguish vascular vertigo from other causes.

PMID- 22377857
TI  - Seizures.
AB  - Seizures can be a clinical presentation of acute stroke or complicate the
      clinical course of patients with stroke. Post-stroke seizures are significantly
      more common in patients with cortical involvement, severe and large size stroke
      and those with cortical hemorrhagic transformation of ischemic stroke. The
      influence of post-stroke seizures on functional outcome is controversial. The
      differences concerning the pathophysiology of and recurrence risk for early and
      late seizures suggests the need for a specific management. The choice of the
      antiepileptic drug will be influenced by the risk of drug interactions and
      possible side effects, especially in the elderly. Currently there is no evidence
      to support the use of antiepileptic drugs in patients with stroke in the absence
      of seizure even in the presence of risk factors for developing seizure.

PMID- 22377856
TI  - Auditory dysfunction.
AB  - Hearing impairment, although uncommon, may occur in patients with a
      vertebrobasilar artery occlusion disease. The pathogenesis may be an ischemic
      lesion involving the auditory pathways in the pons and midbrain, the cochlear
      nucleus, cochlear nerve or the cochlea. The AICA and IAA are the main arteries
      that supply the peripheral audiovestibular structures of the inner ear and
      central audiovestibular pathways of the middle cerebellar peduncle and lateral
      pons.

PMID- 22377858
TI  - Impaired consciousness.
AB  - Coma and other states of impaired consciousness are common in stroke patients.
      Sudden disturbance of consciousness can be the predominant clinical syndrome in
      the brainstem stroke, particularly in the case of basilar artery occlusion.
      Clinicians need to thoroughly investigate for the presence of stroke in patients
      with sudden disturbance of consciousness.

PMID- 22377859
TI  - Sleep changes.
AB  - Sleep difficulties are frequent among stroke patients. Sleep and stroke can be
      related in several ways: sleep disturbances such as insomnia and hypersomnia can
      be triggered by stroke; sleep-related breathing disorders such as snoring and
      sleep apnea are well-recognized risk factors of ischemic stroke; finally, sleep
      disorders can be aggravated by stroke. Sleep problems are associated with all
      stroke types and worsened stroke outcome. Post-stroke sleep disturbances may be a
      direct consequence of lesions caused by stroke or may be secondary to pain,
      disability and mood disorders due to stroke. Clinicians need to thoroughly
      investigate for the presence of sleep disorders in rehabilitating stroke
      patients.

PMID- 22377860
TI  - Aphasia and other language disorders.
AB  - Aphasia refers to a disorder of language processing caused by a dysfunction in
      specific brain regions. It is common after stroke and associated with relevant
      disability and higher mortality. Evaluation of language function (spontaneous
      speech, auditory comprehension, naming, repetition, reading and writing), allows
      classification of aphasia. Most patients present some degree of recovery. Speech
      and language therapy is an effective treatment for aphasia following stroke.
      Other approaches, e.g. pharmacotheraphy, transcranial magnetic stimulation, are
      being investigated. Other language disorders are mentioned.

PMID- 22377861
TI  - Confusion, agitation and delirium.
AB  - Delirium is one of the most serious and common complications that up to one third
      of older patients admitted to hospital develop. It is characterized by a
      disturbance of consciousness, decreased attention, and disorganized thinking that
      develops over a short period of time, and fluctuates during the course of the
      day. Delirium post-stroke prevalence ranges from 13 to 48% in general hospitals,
      and from 10.1 to 28% in Stroke Units. The Confusion Assessment Method and the
      Delirium Rating Scale are used as delirium screening tools. The cause of delirium
      is likely to be multifactorial. In stroke, reduced perfusion of the brain with
      hypoxia, which deranges neurotransmission, may be the cause. Delirium is more
      frequent after intracerebral hemorrhage and infarction in specific brain areas.
      Delirium without other signs of stroke has been reported more often after right
      sided than after left-sided lesions. Age, cognitive decline, and multiple
      coexisting conditions are the most consistent and important risk factors for
      delirium post-stroke. Haloperidol is currently used as the drug of choice, if
      sedation is needed.

PMID- 22377862
TI  - Executive dysfunctions and frontal syndromes.
AB  - Executive functions refer to a set of higher-level abilities that regulate and
      control human goal-directed complex behavior. These functions are a central
      component of the highest level of hierarchical cognitive-behavioral functioning.
      The theoretical construct of an executive system, its subcomponents, and the
      variables that measure them are not clearly defined. The term executive function
      is commonly associated with frontal lobe function, although it is not exclusive
      to the frontal cortex and extends to other regions of the brain. The executive
      system includes higher cognitive, behavioral self-regulatory, and metacognitive
      functions.

PMID- 22377863
TI  - Memory dysfunction.
AB  - Memory is the cognitive ability that allows to acquire, store and recall
      information; its dysfunction is called amnesia and can be a presentation of
      unilateral ischemic stroke in the territory of the posterior cerebral and
      anterior choroidal artery as well as subarachnoid hemorrhage.

PMID- 22377864
TI  - Neurobehavioral syndromes.
AB  - Dysfunction of higher cortical function and neurobehavioral syndromes may be
      present in up to 87% of stroke patients. These symptoms may occur less often in
      patients with transient ischemic attacks (36%). Approximately 22% of stroke
      patients may present only with cognitive and neurobehavioral symptoms without
      elementary neurological deficits. In this chapter we concentrate on delusions,
      hallucinations, misidentification syndromes, anosognosia of hemiplegia,
      aggressive behavior and also extended self syndrome.

PMID- 22377865
TI  - Right hemisphere syndromes.
AB  - Stroke is the leading cause of acquired motor disability in the adult.
      Neuropsychological sequelae are common after vascular brain injury. While left
      cortical signs and symptoms are clearly evident at neurological examination,
      right hemispheric dysfunction must be carefully pursued and sometimes can be
      underrecognized. Indeed, patients with right hemispheric strokes present later to
      an emergency department and have a lower chance of receiving intravenous
      recombinant tissue plasminogen activator. For a better comprehension of clinical
      signs and symptoms in right acute hemispheric stroke, in this chapter we present
      a review of the principle clinical syndromes.

PMID- 22377866
TI  - Post-stroke dementia and cognitive impairment.
AB  - The term post-stroke dementia (PSD) is used to define any dementia occurring
      after stroke irrespective if the leading cause is vascular, degenerative or
      mixed. PSD is a frequent condition after stroke and its prevalence ranges from 6
      to 32%. However, not all cognitive impairment cases following a stroke are enough
      severe to fit the criteria for dementia. Indeed, many patients after a stroke
      develop mild cognitive impairment that in some cases can progress to PSD. There
      is an urgent need to find sensitive tools to detect post-stroke cognitive
      impairment as early as possible. The detection of cognitive impairment in the
      acute phase of stroke can offer valid information to the clinician on whether to
      set an early cognitive rehabilitation and to plan a more focused follow-up.

PMID- 22377867
TI  - Mood disorders after stroke.
AB  - Mood disorders occurring after stroke are a major concern to public health as
      they are frequent, difficult to diagnose and to treat, and have high impact on
      the quality of life of patients and caregivers. The association of manic symptoms
      (rare) in the acute phase of stroke with strategic locations within the right
      hemisphere is clinically significant. However, the link among poststroke
      depression and anxiety (most prevalent), brain circuitries, clinical signs and
      individual psychological factors is not yet disentangled. The involvement of too
      many variables produces methodological difficulties and, therefore, the findings
      of a great number of studies are not systematically replicated. Thus, there is a
      need for research in this area of stroke medicine. Investigations on poststroke
      mood disorders might increase insight into the pathogenesis of mood disorders
      (which share the same clinical profile) occurring in people without brain
      lesions.

PMID- 22377868
TI  - Agnosia, apraxia, callosal disconnection and other specific cognitive disorders.
AB  - Cortical function deficits have long been studied by anatomoclinic correlations.
      Recent functional imaging studies have allowed scientists to better understand
      which cerebral areas and which networks are involved in cognitive function
      deficit. This chapter will review the current knowledge on agnosia, apraxia and
      callosal disconnection syndromes.

PMID- 22377869
TI  - Muscle, peripheral nerve and autonomic changes.
AB  - Muscle, peripheral nerve and autonomic disorders associated with acute
      cerebrovascular events are a large spectrum of conditions, their pathophysiology,
      clinical features, frequencies of occurrence, prognosis and treatment are
      diverse; the disturbances may be primary or secondary to acute cerebrovascular
      events. These disorders have been previously defined as multiple neurological
      complications as the underlying pathophysiological mechanism may largely differ;
      their characterization may need a full clinical, neuroradiological,
      neurophysiological, immunological, biochemical and genetic analyses assessment,
      and an autonomic function test may also be needed as well as nerve and muscle
      biopsy. In this chapter we present multiple neurological complications secondary
      to acute cerbrovascular events.

PMID- 22377870
TI  - Dysarthria and mutism.
AB  - Dysarthria is a speech disorder associated with impairments of intelligibility,
      smoothness, loudness, and clarity of articulations. Dysarthria involves
      disability of reproducing various physical, tonal, and sound features of speech
      sounds in oral speech; unintelligible and slurred articulation with swallowing of
      sounds is characteristic. Articulatory movements and speech are slow, patients
      complain to the sensations of a 'thick' tongue and 'porridge' in the mouth.
      Patients'phrases are constructed correctly, vocabulary is not affected, and the
      grammatical structure of words is preserved. Reading, writing, internal speech,
      and understanding of speech are unaffected. Several types of dysarthria have been
      described on the basis of the lesion locations. Dysarthria can be associated with
      lacunar syndromes as well. Mutism represents a condition when patient cannot
      speak and answer the questions, but remains conscious and is able to produce
      written speech.

PMID- 22377871
TI  - Dysphagia--pathophysiology, diagnosis and treatment.
AB  - Dysphagia is an extremely common disorder after stroke, affecting as many as half
      of acute stroke sufferers. It is associated with respiratory complications,
      increased risk of aspiration pneumonia, nutritional compromise and dehydration,
      and detracts from quality of life. For this reason, dysphagia significantly
      affects outcome and is associated with increased morbidity and mortality. Formal
      dysphagia screening protocols significantly reduce the rate of pneumonia and
      improve general outcome. Furthermore, early behavioral swallowing interventions
      are associated with a more favorable outcome in dysphagic stroke patients. This
      chapter reviews the pathophysiology of swallowing dysfunction, and the diagnosis
      and treatment of patients with dysphagia after an acute stroke.

PMID- 22377872
TI  - Ventilatory disorders.
AB  - Breathing is a primal homeostatic neural process, regulating levels of oxygen and
      carbon dioxide in blood and tissues, which are crucial for life. Rhythmic
      respiratory movements must occur continuously throughout life and originate from
      neural activity generated by specially organized macro- and microcircuits in the
      brainstem. In the respiratory network there is a spatial and dynamic hierarchy of
      interacting circuits, each of which controls different aspects of respiratory
      rhythm generation and pattern formation, which can be revealed as the network is
      progressively reduced. The motor pattern during normal breathing is considered to
      consist of three phases: inspiration, post-inspiration and expiration. The
      expression of each rhythmogenic mechanism is state-dependent and produces
      specific motor patterns likely to underpin distinct motor behaviors. Vascular
      neurological disorders affecting these areas or the respiratory motor unit may
      lead to impaired respiratory activity. Manifestations associated with disorders
      of this network include sleep apnea and dysrhythmic breathing frequently
      associated with disturbances of cardiovagal and sympathetic vasomotor control.
      Respiratory dysfunction constitutes an early and relatively major manifestation
      of vascular neurologic disorders; ventilation control and breathing behavior
      correction are necessary to improve stroke management.

PMID- 22377873
TI  - Lacunar versus non-lacunar syndromes.
AB  - Small-vessel disease is the accepted most frequent cause of lacunar stroke. The
      main clinical features seen with lacunar infarcts are motor and/or sensitive
      deficit, ataxic sign, without cortical involvement. A lacunar syndrome is
      generally the result of a small deep infarct within the territory of a single
      perforating artery with the maximum diameter on imaging of 15 mm. Recent studies
      have demonstrated alternative causes of lacunar stroke other than small-vessel
      disease (e.g. cardio embolism, atherosclerosis or other causes), especially in
      large lacunae, with a potential relevance on functional outcome. These findings
      suggest that lacunar stroke is not always a benign disease. Moreover, clinical
      features may be significant in terms of disability in lacunae in close proximity
      to crucial anatomical site. The following chapter reports the classical lacunar
      syndrome and discusses the debated etiology of lacunar stroke.

PMID- 22377874
TI  - Arterial territories of the human brain.
AB  - We present a brain map of the areas supplied by various arteries in the
      brainstem, cerebellum and cerebral hemispheres. Arterial territories are depicted
      in a form that is directly applicable to neuroimaging slices in clinical
      practice. The arterial territories are outlined based on an extensive overview of
      anatomical studies of cerebral blood supply. For arterial territories of the
      hemispheres, we present the variability of the cortical territories of the three
      main cerebral arteries and define the minimal and maximal cortical supply areas.

PMID- 22377875
TI  - Superficial middle cerebral artery territory infarction.
AB  - The superficial middle cerebral artery (MCA) territory includes the greater part
      of the lateral surface of the cerebral hemisphere. It is the most frequent
      infarct in MCA ischemic cerebrovascular pathology. It is divided into 12 areas
      supplied by 12 different arteries referred to as the irrigated areas; however,
      anatomical variations should be considered in these infarcts. Clinical
      symptomatology depends on the artery affected (changes in personality, judgment
      or motor synchronization disturbances, disorientation, hemianopia or
      hemineglect), but more frequently there is an overlapping of artery infarcts
      (insular syndrome and sensitive, motor or language disturbances). Embolic
      mechanism remains the main etiology of these infarcts, but due to different
      etiological mechanisms of ischemic stroke, an extensive neurovascular and
      cardiological assessment is essential for the correct treatment of the patient.

PMID- 22377876
TI  - Lenticulostriate infarction.
AB  - Lenticulostriate infarcts result from ischemia within the territory supplied by
      the deep perforating branches of the middle cerebral artery (MCA). They are too
      often associated with infarctions of the deep perforating branches of the
      internal carotid artery. Lenticulostriate arteries usually arise from the main
      trunk of the MCA, but can emerge from the cortical branches. The clinical aspects
      of lenticulostriate infarction should be properly differentiated from those of
      other anterior circulation infarcts. Clinical signs include motor deficit,
      sensory deficit and cognitive dysfunction. The principal mechanism for
      lenticulostriate infarction seems to be an embolism of cardiac origin. The
      concept of lacunar infarctions relating to lipohyalinosis is perhaps too often
      proposed without evidence. The prognosis is dependent primarily on the intensity
      of damage to the upper part of the posterior limb of the internal capsule. They
      are terminal arteries without anastomoses, making them more susceptible to
      ischemia and resulting in a greater risk of arteriolar necrosis and hemorrhagic
      transformation.

PMID- 22377877
TI  - Anterior cerebral artery and Heubner's artery territory infarction.
AB  - Anterior cerebral artery (ACA) territory strokes account for 0.5-3% of all
      ischemic strokes. The etiological mechanisms of ACA territory strokes vary by
      race; ACA dissection is a frequent cause in Japan. The most prevalent symptom of
      such strokes is contralateral hemiparesis or monoparesis, usually affecting the
      leg predominantly. Predominant leg weakness is attributed to damage in the
      paracentral lobule, and weakness of the arm and face is associated with
      involvement of Heubner's artery and the medial striate arteries. Hypobulia,
      typically 'akinetic mutism', is also common. Several behavioral disorders,
      including the grasp reflex and the alien hand sign, can present as callosal
      disconnection signs. Transcortical aphasia and urinary incontinence are other
      frequent symptoms. A non-throbbing headache is common at stroke onset in patients
      with ACA dissection.

PMID- 22377878
TI  - Anterior choroidal artery territory infarction.
AB  - The anterior choroidal artery (AChA) originates from the posterior wall of the
      internal carotid distal to the posterior communicating artery and proximal to the
      intracerebral carotid bifurcation. This thin artery is rarely the cause of
      aneurysm and only accounts for 2-5% of all aneurysms. Even though the AChA
      territory shows large variations among individuals, it supplies crucial motor and
      sensory structures, such as the internal capsule, optic tract, the posterior limb
      of the internal capsule, the cerebral peduncle, and the choroid plexus.

PMID- 22377879
TI  - Posterior cerebral artery territory infarctions.
AB  - Infarctions in the territory of the posterior cerebral artery (PCA) occur in
      about 5-10% of all ischemic strokes. The PCA can be divided into 'deep' (P1 and
      P2 segments) and 'superficial' (P3 and P4) segments. Occlusion of paramedian
      perforating arteries arising from P1 causes rostral midbrain infarction with or
      without thalamic lesion. The classical clinical triad after thalamomesencephalic
      infarcts is hypersomnolence, cognitive deficits and vertical oculomotor paresis.
      Two main arterial groups arise from P2: infarction in the territory of the
      thalamogeniculate arteries causes severe contralateral hypesthesia and ataxia,
      whereas infarction in the territory of the posterior choroidal arteries results
      in sectoranopia with involvement of the lateral geniculate body. After
      superficial PCA infarcts, visual field defects and somatosensory deficits are the
      most frequent signs. Additionally, disorders of reading may be seen after
      unilateral left infarction and disorientation for place and visual neglect after
      right lesion. After bilateral PCA infarcts, amnesia, cortical blindness (the
      patient cannot see but pretend he can) may occur. Acute thrombolysis is as useful
      after PCA infarctions as after anterior circulation strokes. Mortality after PCA
      strokes is low, but long-term behavioral and cognitive deficits are
      underestimated.

PMID- 22377880
TI  - Thalamic infarcts and hemorrhages.
AB  - The anatomy and supply of thalamic arteries are briefly described here. Thalamic
      infarcts and small-size hemorrhages are classified according to their sites: (1)
      posterolateral, (2) anterolateral, (3) medial, and (4) dorsal. (1) Posterolateral
      hemorrhages or lateral thalamic infarcts are usually characterized by severe
      motor impairment and sensory loss. Transient reduced consciousness, vertical-gaze
      abnormalities, and small fixed pupils may be evidenced. (2) Patients with
      anterolateral hemorrhages or tuberothalamic artery infarcts present frontal-type
      neuropsychological symptoms associated with mild hemiparesis and hemihypesthesia.
      (3) Medially located hemorrhages or paramedian artery infarcts have decreased
      levels of consciousness, vertical- and horizontal-gaze abnormalities, amnesia,
      and abulia. (4) Dorsal hemorrhages or posterior choroidal artery infarcts present
      with minimal transient hemiparesis and hemihypesthesia; apraxia, aphasia, and
      amnesia have also been described.

PMID- 22377881
TI  - Caudate infarcts and hemorrhages.
AB  - The caudate nucleus (CN) is composed of a head, body and tail. The head of the CN
      contributes to forming the floor of the lateral ventricle frontal horn. Moreover,
      the head, which is medially separated by the septum pellucidum extends beyond the
      anterior part of the thalamus, stroking the telencephalic cortex. The superior
      part of the head is covered by the knee of the corpus callosum, while the
      inferior part is below the thalamus and lenticular nucleus, which delimits the
      internal capsule. CN strokes are classified into hemorrhagic and ischemic. The
      clinical presentation of CN hemorrhage is often characterized by a clinical
      presentation mimicking subarachnoid hemorrhage, while clinical features of both
      ischemic and hemorrhagic strokes included behavioral abnormalities dysarthria,
      movement disorders, language disturbances and memory loss. Most studies to date
      that have examined vascular CN pathologies have evidenced good outcomes.

PMID- 22377882
TI  - Putaminal hemorrhages.
AB  - The putamen is a common site of hypertensive cerebral hemorrhage. Such
      hemorrhages show a large range of possible presentations - from enormous
      hemorrhages involving the white matter of the hemispheres and the ventricular
      system, to cases occurring without causing any symptoms or neurological signs.
      The symptoms of onset, the clinical evolution and the outcome are largely due to
      the magnitude of the initial blood extravasation. This chapter describes typical
      as well as rare clinical manifestations of putaminal hemorrhages.

PMID- 22377883
TI  - Lobar hemorrhages.
AB  - The lobar localization of a spontaneous intracerebral hemorrhage occurs in one
      third of all cases; the most frequent cause is represented by amyloid angiopathy.
      The clinical symptomatology depends on the dimensions of the hematic collection
      and of the lobe. The diagnosis is made by CT, but also MRI must performed in
      order to exclude any vascular malformation or neoplasms, and in young patients a
      cerebral angiography must be done in order to exclude small arteriovenous or
      dural malformations.

PMID- 22377884
TI  - Subarachnoid and intraventricular hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) accounts for 5% of all strokes but its burden is
      relevant due to high mortality, high disability and a remarkable incidence in the
      young. The rupture of an intracranial aneurysm is responsible for about 85% of
      SAHs; 10% are represented by non-aneurysmal conditions; 5% are represented by
      other medical conditions such as inflammatory or non-inflammatory lesions of
      cerebral artery, coagulopathy, neoplasms or drug abuse. The clinical presentation
      of a SAH can be extremely variable ranging from nearly asymptomaticity to sudden
      death. Rebleeding is the most frequent and severe complication of SAH. The
      aneurysm exclusion is the most effective treatment for preventing rebleeding.
      Endovascular occlusion of the aneurysm with coils has been shown to be associated
      with better short- and long-term outcomes than surgical clipping in select
      patients.

PMID- 22377885
TI  - Large middle cerebral artery and panhemispheric infarction.
AB  - Large middle cerebral artery (MCA) and panhemispheric stroke represent a minority
      of cerebral ischemic events, yet they are responsible for a disproportionate
      share of morbidity and mortality. Malignant infarction with formation of cerebral
      edema is a common cause for secondary neurologic deterioration. Despite intensive
      medical and surgical care, prognosis is often poor and mortality may be as high
      as 60-80%. Surgical intervention can reduce that mortality compared to medical
      therapy alone, but necessitates a careful exploration of patient characteristics
      for acceptable outcomes.

PMID- 22377886
TI  - Midbrain infarcts and hemorrhages.
AB  - The vascular supply of this small brainstem structure is complex. Although
      midbrain infarcts and particularly hemorrhages are uncommon, their clinical
      manifestations are diverse mainly because the vertical gaze centers and two of
      three nuclei of the extraocular muscles lie primarily in the midbrain.
      Consequently, eye movement disturbances are often the hallmark clinical findings
      in midbrain stroke. The main clinical patterns, etiology and outcome of infarcts
      limited to the midbrain are summarized according to defined vascular territories
      along with the clinical findings of midbrain hemorrhage.

PMID- 22377887
TI  - Pontine infarcts and hemorrhages.
AB  - Pontine infarcts are often part of a large ischemia involving the brainstem,
      although infarcts may be restricted to the pons. In both cases, infarcts in the
      pons are characterized by interesting clinical patterns resulting from a variety
      of cranial nerve dysfunctions, eye movement disorders and motor, sensory and
      cerebellar manifestations, either isolated or in combination. The anteromedial
      and anterolateral territories are the most commonly involved. Penetrating branch
      artery disease is the most common etiology. Ten percent of all intracerebral
      hemorrhages are located in the pons, and small hemorrhages in this brainstem
      structure may, in some instances, give rise to unusual clinical manifestations.

PMID- 22377888
TI  - Medullary infarcts and hemorrhages.
AB  - Even though advances in noninvasive imaging of the brain have simplified the
      diagnostic of medullary strokes, clinical recognition can be still challenging.
      This chapter describes typical as well as rare clinical manifestations of
      medullary strokes to help clinicians' recognition of this rare but potentially
      life-threatening disease. It also contains imaging information useful to identify
      areas likely to be affected by strokes with resulting distinct syndromes.

PMID- 22377889
TI  - Cerebellar infarcts and hemorrhages.
AB  - Cerebellar infarction accounts for about 3.4% of all ischemic strokes. Cerebellar
      syndromes are principally characterized by cerebellar symptoms and signs which
      depend on the involved vascular territories. In the Perugia Stroke Registry,
      infarct areas have included the superior cerebellar artery region in 36% of
      patients, the anterior inferior cerebellar artery region in 12%, and the
      posterior inferior cerebellar artery region in 40%; 12% of patients have had
      multiple vascular region involvement. 50% of the patients have had concurrent
      brainstem infarcts. Cerebellar hemorrhage accounts for about 10% of all
      intracranial hemorrhages and about 10% of all cerebellar strokes. Both stroke
      types can be worsened by complications due to a significant mass effect and
      brainstem compression. These events can lead to clinical deterioration which
      induces stupor and coma with a very high fatality rate.

PMID- 22377890
TI  - Extended infarcts in the vertebrobasilar territory.
AB  - Posterior circulation stroke accounts for about 20% of all ischemic strokes in a
      variety of syndromic pictures ranging from lacunar and limited infarcts to more
      extensive involvement. Furthermore, infarcts in the vertebrobasilar (VB) region
      are frequently multiple and not univocally identifiable in one single clinical
      entity; the prognosis is sometimes unpredictable and very often is unfavorable
      having a high early mortality rate. The basilar artery (BA), which is the main
      vessel of the posterior circulation, supplies most of the brainstem and occipital
      lobes and part of the cerebellum and thalami, its occlusion (BAO) is the most
      severe occurrence in the posterior circulation infarct context. The optimum
      management of BAO is still under debate and in the absence of randomized studies
      the most appropriate approach is still unclear. In the previous chapters, single
      territory infarcts involving the posterior circulation have been discussed. The
      present chapter will discuss extended infarcts in the VB territory due to
      different degrees of VB involvement or to BAO.

PMID- 22377891
TI  - Border-zone and watershed infarctions.
AB  - Border-zone (BZ) and watershed infarcts occur at the junction of two artery
      territories and are precipitated by a hemodynamic impairment although they cannot
      be excluded from microembolic etiology. These strokes may often be preceded by
      specifically precipitating circumstances that induce hypotension and/or
      hypovolemia (rising from a supine position, exercise, Valsalva's maneuver,
      administration of antihypertensive drugs, bleeding and anemia). Anterior BZ
      infarction occurs with a motor deficit of one or both contralateral limbs,
      associated with aphasia or mood disturbance. Campimetric disturbances are a
      constant feature of posterior BZ infarct associated with fluent aphasia and
      hemihypoesthesia. Subcortical and capsule-thalamic BZ infarctions often mimic
      lacunar syndrome due to small-vessel disease. Cerebellar BZ infarction is
      associated with non-specific vertigo syndrome or ataxia, while in brainstem BZ
      infarction patients are comatose with other signs of brainstem being compromised.

PMID- 22377892
TI  - Acute and chronic carotid occlusion syndromes.
AB  - Clinical manifestations of acute internal carotid artery (ICA) occlusion are the
      most variable among all cerebrovascular syndromes. This extreme variability is
      related essentially to three variables: collateral circulation, cerebral
      vasoreactivity with hemodynamic factors, and the characteristics of occlusion.
      Intracranial circulation is represented by a mirabilis network connecting both
      anterior-posterior and deep-shallow circulation systems. The compensation
      mechanisms in ICA occlusion can be influenced by preexisting risk factors.
      Moreover, an alteration in cerebral hemodynamic function related to previous
      stroke, chronic hypoperfusion and vascular risk factors play a relevant role in
      the clinical features of ICA occlusion. On the other hand, also after an acute
      event, the clinical evolution in a patient with ICA occlusion, which is defined
      here as chronic occlusion, is extremely variable: some patients remain
      asymptomatic, while others suffer recurrent TIA or minor/major stroke. The
      factors set forth above associated with other underlying conditions also affect
      clinical development. However, a fundamental role is played by the proper
      management of vascular risk factors whether in acute or chronic ICA occlusion.

PMID- 22377893
TI  - Venous ischemic syndromes.
AB  - Venous ischemic syndromes represent a rare type of cerebrovascular disease that
      more commonly affects young women. Because of the remarkable variability of
      clinical presentations and neuroimaging signs, these syndromes represent an
      important clinical challenge. The most common clinical presentations include
      headache, seizures, focal neurological deficits, altered consciousness, and
      papilledema, which can present in isolation or in association with other
      symptoms. According to the grouping of symptoms and signs, four main patterns
      have been identified: isolated intracranial hypertension, focal syndrome,
      cavernous sinus syndrome, and subacute encephalopathy. CT scan is commonly
      performed as the first-line diagnostic test, in most cases showing indirect signs
      such as cerebral edema, ischemic or hemorrhagic lesions, or signs of venous
      stasis. The most accurate diagnostic techniques to objectively confirm the
      diagnosis include magnetic resonance angiography and computed tomography
      angiography. Clinical presentations and neuroimaging signs are important
      predictors of outcome following venous ischemic syndromes. Coma, epileptic
      seizures and intracranial hemorrhage were shown, among others, to be independent
      predictors of poor outcome.

PMID- 22377894
TI  - Spinal cord syndromes.
AB  - Spinal cord infarction is much rarer than cerebral stroke, but its early
      recognition is important as it may signify serious aortic conditions. The most
      frequent type is anterior spinal artery syndrome, presenting with bilateral
      weakness (usually paraparesis), impairment of spinothalamic sensation and
      preservation of deep sensation. Depending on its level, it may present with
      respiratory dysfunction. More rarely, posterior infarcts sparing spinothalamic
      sensation but involving lemniscal sensation may be encountered. Unilateral,
      central or transverse infarction may also be seen probably on account of
      different mechanisms. Other rarer forms of spinal ischemia also include spinal
      TIAs, venous infarction, fibrocartilaginous embolism and decompression sickness.

PMID- 22377895
TI  - Rapid identification of non-human sequences in high-throughput sequencing
      datasets.
AB  - Rapid identification of non-human sequences (RINS) is an intersection-based
      pathogen detection workflow that utilizes a user-provided custom reference genome
      set for identification of non-human sequences in deep sequencing datasets. In <2
      h, RINS correctly identified the known virus in the dataset SRR73726 and is
      compatible with any computer capable of running the prerequisite alignment and
      assembly programs. RINS accurately identifies sequencing reads from intact or
      mutated non-human genomes in a dataset and robustly generates contigs with these
      non-human sequences (Supplementary Material). AVAILABILITY: RINS is available for
      free download at http://khavarilab.stanford.edu/resources.html.

PMID- 22377896
TI  - Sequencing histone-modifying enzymes identifies UTX mutations in acute
      lymphoblastic leukemia.

PMID- 22377897
TI  - Evaluating surface erythropoietin receptor in multiple myeloma.

PMID- 22377898
TI  - Outcome of patients activating an unrelated donor search: the impact of
      transplant with reduced intensity conditioning in a large cohort of consecutive
      high-risk patients.
AB  - An unrelated donor (UD) search was submitted to the Italian Bone Marrow Donor
      Registry between February 2002 and December 2004, for 326 consecutive patients
      with hematological malignancies, eligible for a reduced intensity conditioning
      (RIC) UD transplant. Only two regimens were allowed: melphalan, alemtuzumab,
      fludarabine and total body irradiation of 200 cGy (regimen A) and thiotepa,
      cyclophosphamide, anti-thymocyte globulin (regimen B). The outcome of patients
      receiving an UD transplant (n=121) was compared with patients who did not find a
      donor (n=205), in a time dependent analysis, correcting for time to transplant.
      The median follow up from activation of donor search was 6.1 years. UD transplant
      was associated with a significantly better survival in patients with acute
      leukemia and non-Hodgkin's lymphoma (NHL) whereas only a favorable trend was
      documented for Hodgkin's disease. No survival benefit was registered for chronic
      leukemias. The outcome of the two different conditioning regimens was comparable,
      in terms of survival, transplant-related mortality and graft versus host disease.
      In conclusion, finding an UD and undergoing a RIC transplant significantly
      improves survival of patients with acute leukemia and NHL. The advantage is less
      clear for HD and chronic leukemias. The role of different conditioning regimens
      remains to be elucidated by prospective clinical trials.

PMID- 22377899
TI  - Non-hydrolytic sol-gel routes to heterogeneous catalysts.
AB  - Oxides and mixed oxides have a tremendous importance in the field of
      heterogeneous catalysis, serving either as catalysts or as supports for active
      species. The performance of a catalyst depends directly on its composition,
      texture, structure and surface properties, which have to be precisely controlled
      and adapted to each application. In this context, the sol-gel process is a unique
      tool for the preparation and understanding of catalytic materials, owing to its
      exceptional versatility. In the last 10 years, the non-hydrolytic sol-gel (NHSG)
      or non-aqueous sol-gel process based on nonhydrolytic condensations in nonaqueous
      media has established itself as a simple and powerful method for the design of a
      wide range of oxide, mixed oxide and hybrid materials with controlled
      composition, morphology, texture and structure. NHSG proved particularly
      interesting for the preparation of catalytic materials, notably mesoporous
      xerogels, single site catalysts and highly crystalline nanoparticles. This
      critical review addresses the application of NHSG to the preparation of
      heterogeneous catalysts, emphasizing the specificities of this process, and
      giving a comprehensive overview of the literature (251 references).

PMID- 22377900
TI  - Target molecules of food phytochemicals: food science bound for the next
      dimension.
AB  - Phytochemicals are generally defined as secondary metabolites in plants that play
      crucial roles in their adaptation to a variety of environmental stressors. There
      is a great body of compelling evidence showing that these metabolites have
      pronounced potentials for regulating and modulating human health and disease
      onset, as shown by both experimental and epidemiological approaches.
      Concurrently, enormous efforts have been made to elucidate the mechanism of
      actions underlying their biological and physiological functions. For example, the
      pioneering work of Tachibana et al. uncovered the receptor for (-)
      epigallocatechin-3-gallate (EGCg) as the 67 kDa laminin receptor, which was shown
      to partially mediate the functions of EGCg, such as anti-inflammatory, anti
      allergic, and anti-proliferative activities. Thereafter, several protein kinases
      were identified as binding proteins of flavonoids, including myricetin,
      quercetin, and kaempferol. Isothiocyanates, sulfur-containing phytochemicals
      present in cruciferous plants, are well known to target Keap1 for activating the
      transcription factor Nrf2 for inducing self-defensive and anti-oxidative gene
      expression. In addition, we recently identified CD36 as a cell surface receptor
      for ursolic acid, a triterpenoid ubiquitously occurring in plants. Importantly,
      the above mentioned target proteins are indispensable for phytochemicals to
      exhibit, at least in part, their bioactivities. Nevertheless, it is reasonable to
      assume that some of the activities and potential toxicities of metabolites are
      exerted via their interactions with unidentified, off-target proteins. This
      notion may be supported by the fact that even rationally designed drugs
      occasionally display off-target effects and induce unexpected outcomes, including
      toxicity. Here we update the current status and future directions of research
      related to target molecules of food phytochemicals.

PMID- 22377901
TI  - Methylmercury bioaccumulation in invertebrates of boreal streams in Norway:
      effects of aqueous methylmercury and diet retention.
AB  - Transfer of aqueous methylmercury (MeHg) to primary consumers in aquatic foodwebs
      is poorly understood despite its importance for bioaccumulation of MeHg. We
      studied bioaccumulation of MeHg in simple aquatic food chains of two humic boreal
      streams in relation to streamwater chemistry, food web characteristics and
      dietary fatty acid (FA) biomarkers. Transfer of aqueous MeHg into primary
      consumers was similar in both streams, resulting in higher MeHg in consumers in
      the MeHg-rich stream. Trophic enrichment of MeHg and dietary retention of FA
      biomarkers was the same in both streams, suggesting that exposure to aqueous MeHg
      at the base of the food chain determined levels of MeHg in biota. In addition,
      contents of dietary biomarkers suggested that ingestion of algae reduced MeHg
      bioaccumulation, while ingestion of bacteria stimulated MeHg uptake. Dietary
      uptake of bacteria could thus be an important pathway for MeHg-transfer at the
      bottom of food chains in humic streams.

PMID- 22377902
TI  - Lead phytotoxicity in soils and nutrient solutions is related to lead induced
      phosphorus deficiency.
AB  - This study was set up to relate lead (Pb) bioavailability with its toxicity to
      plants in soils. Tomato and barley seedlings were grown in six different PbCl(2)
      spiked soils (pH: 4.7-7.4; eCEC: 4.2-41.7 cmol(c)/kg). Soils were leached and pH
      corrected after spiking to exclude confounding factors. Plant growth was halved
      at 1600-6500 mg Pb/kg soil for tomato and at 1900-8300 mg Pb/kg soil for barley.
      These soil Pb threshold were unrelated to soil pH, organic carbon, texture or
      eCEC and neither soil solution Pb nor Pb(2+) ion activity adequately explained Pb
      toxicity among soils. Shoot phosphorus (P) concentrations significantly decreased
      with increasing soil Pb concentrations. Tomato grown in hydroponics at either
      varying P supply or at increasing Pb (equal initial P) illustrated that shoot P
      explained growth response in both scenarios. The results suggest that Pb toxicity
      is partially related to Pb induced P deficiency, likely due to lead phosphate
      precipitation.

PMID- 22377903
TI  - Depleted soil carbon and nitrogen pools beneath impervious surfaces.
AB  - Urban soils and vegetation contain large pools of carbon (C) and nitrogen (N) and
      may sequester these elements at considerable rates; however, there have been no
      systematic studies of the composition of soils beneath the impervious surfaces
      that dominate urban areas. This has made it impossible to reliably estimate the
      net impact of urbanization on terrestrial C and N pools. In this study, we
      compared open area and impervious-covered soils in New York City and found that
      the C and N content of the soil (0-15 cm) under impervious surfaces was 66% and
      95% lower, respectively. Analysis of extracellular enzyme activities in the soils
      suggests that recalcitrant compounds dominate the organic matter pool under
      impervious surfaces. If the differences between impervious-covered and open area
      soils represent a loss of C and N from urban ecosystems, the magnitude of these
      losses could offset sequestration in other parts of the urban landscape.

PMID- 22377904
TI  - One year intensive PM2.5 bound polycyclic aromatic hydrocarbons monitoring in the
      area of Tuscany, Italy. Concentrations, source understanding and implications.
AB  - Polycyclic aromatic hydrocarbons (PAHs) associated to PM(2.5) particles were
      monitored at three sites in the region of Tuscany, Italy, during the period March
      2009-March 2010. PAH concentrations ranged between 0.92 ng m(-3) and 13 ng m(-3).
      The spatial and seasonal differences observed at the three sites are discussed
      and attributed to specific PAH sources. Benzo[a]Pyrene average annual values were
      below the EU limit value of 1.0 ng m(-3). The results of this study suggest that
      emissions from commuting and work related traffic play an important role for the
      city of Florence, whereas for the city of Livorno, the harbor activities seem to
      impact the PAH burden substantially, as well. The PAH cancer risk (expressed as
      the "BaPE index") has shown a 6-fold decline compared to early 1990's
      concentrations and 2- to 3-fold decline compared to the late 1990's.

PMID- 22377905
TI  - Cytoarchitectural characteristics of hippocampal CA1 pyramidal neurons of rats,
      four months after global cerebral ischemia and progesterone treatment.
AB  - PURPOSE: To analyze the cytoarchitectural characteristics of the remaining
      pyramidal neurons in the hippocampal CA1 subfield of rats, four months after
      global cerebral ischemia (GCI) and progesterone treatment. METHODS: Dendritic
      arborization, and density and shape of the dendritic spines of CA1 pyramidal
      neurons in brains of intact rats, or rats submitted 120 days earlier to GCI and
      treatment with progesterone (8 mg/kg) or its vehicle, at 15 min, and 2, 6, 24,
      48, and 72 h after the onset of reperfusion, were analyzed in samples processed
      by a modified Golgi method. RESULTS: Few impregnated CA1 pyramidal neurons were
      identified in the ischemic vehicle-treated rats, with a short apical dendrite
      devoid of bifurcations and dendritic spines. In contrast, the remaining CA1
      pyramidal neurons sampled from ischemic progesterone-treated rats showed
      sinuously branched dendrites with similar number of bifurcations and whole
      density of spines, and higher proportional density of mushroom spines than those
      in the intact group. CONCLUSIONS: These cytoarchitectural characteristics may
      underlie the long-term preservation of place learning and memory functions seen
      after ischemia and progesterone neuroprotective treatment, possibly compensating
      for the severe reduction in neuronal population.

PMID- 22377906
TI  - Ibuprofen attenuates the inflammatory response and allows formation of migratory
      neuroblasts from grafted stem cells after traumatic brain injury.
AB  - PURPOSE: There is hope for neural stem and progenitor cells (NSPC) to enhance
      regeneration when transplanted to the injured brain after traumatic brain injury
      (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered
      mainly by the notable death of the transplanted cells. Neuroinflammation may lead
      to additional cell death after TBI and we hypothesized that survival of grafted
      NSPC could be enhanced by anti-inflammatory treatment. METHODS: Mice that were
      subjected to controlled cortical impact TBI and grafted with NSPC, were treated
      with the non-steroidal anti-inflammatory drug ibuprofen. RESULTS: Ibuprofen was
      found to down-regulate the TBI-induced inflammatory response. In addition,
      migrating neuroblasts from transplanted cells were observed near the contusion
      and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting
      that the anti-inflammatory treatment had beneficial effects on graft survival
      and/or differentiation. However, Morris Water Maze performance or TBI-induced
      tissue loss was not influenced by ibuprofen treatment. CONCLUSIONS: Our data
      suggests that anti-inflammatory strategies may be a complement to enhance the
      outcome for the cell transplants following TBI.

PMID- 22377907
TI  - Third trimester amniotic fluid cells with the capacity to develop neural
      phenotypes and with heterogeneity among sub-populations.
AB  - PURPOSE: Our aim was the search for new sources of cells potentially useful for
      central nervous system regenerative medicine. Extra-embryonic tissues are
      promising sources of pluripotent stem cells. Among these, human second-trimester
      amniotic fluid (AF) contains cell populations exhibiting self-renewal capacity,
      multipotency and the expression of embryonic cell markers. METHODS: Here we
      report the properties of the easily available third-trimester AF cells (AFCs).
      Different cell types from 6 of 9 AF samples were separated, expanded, and
      characterized by assessing their morphological, proliferative, and
      differentiative properties. RESULTS: All isolated cultures presented CD105, CD90
      and CD73 mesenchymal markers, whereas they differed among themselves in CD117,
      CD146, CD31, NG2 and CD133 expression. Their doubling time and telomere length
      were conserved throughout many passages. Importantly, immunofluorescence and Real
      time PCR showed that, during their proliferative state and differentiation,
      several cultures expressed neuronal and glial markers such as nestin, GFAP, beta
      tubulin III and neurofilament H indicating their potential attitude towards a
      neural fate. Indeed, these cells showed a rather poor capacity to differentiate
      in adipogenic and osteogenic lineages. CONCLUSIONS: In this work we report that
      cells with neural differentiation capability can be isolated from third-trimester
      AF, such properties could be useful for neuro-regenerative purposes.

PMID- 22377909
TI  - Sport concussion knowledge in the UK general public.
AB  - This is the first study to assess sport concussion knowledge and the effect of
      sport concussion self-report on knowledge in the UK general public. In the online
      survey, participants (n = 227) stated personal sport concussion history, injury
      indicators, and rated 26 injury statements for truthfulness using definite (true,
      false) or non-definite (probably true, probably false) response options. As
      anticipated, knowledge was limited. Few statement ratings were definite, and
      misconceptions prevailed. The injury's seriousness was systematically
      underestimated, suggesting that knowledge may not be sufficient for injury self
      diagnosis and self-recovery measures. Sport concussion self-report was associated
      with more definite than non-definite statement ratings. However, response
      accuracy did not differ. This suggested that personal injury experience may yield
      a false sense of security. The use of accessible, easy-to-use tools needs to be
      promoted to improve sport practice safety.

PMID- 22377908
TI  - Synthetic lethal targeting of DNA double-strand break repair deficient cells by
      human apurinic/apyrimidinic endonuclease inhibitors.
AB  - An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA
      Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1).
      APE1 is essential for BER and an emerging drug target in cancer. We have isolated
      novel small molecule inhibitors of APE1. In this study, we have investigated the
      ability of APE1 inhibitors to induce synthetic lethality (SL) in a panel of DNA
      double-strand break (DSB) repair deficient and proficient cells; i) Chinese
      hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79)
      and BRCA2 revertant [V-C8(Rev1)]. ii) Human cancer cells: BRCA1 deficient (MDA-MB
      436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX
      cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested SL in
      CH ovary cells expressing a dominant-negative form of APE1 (E8 cells) using ATM
      inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are
      synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in
      accumulation of DNA DSBs and G2/M cell cycle arrest. SL was also demonstrated in
      CH cells expressing a dominant-negative form of APE1 treated with ATM or DNA-PKcs
      inhibitors. We conclude that APE1 is a promising SL target in cancer.

PMID- 22377910
TI  - Using the contralateral reverse less invasive plating system for subtrochanteric
      femur fractures in elderly patients.
AB  - OBJECTIVE: In this retrospective study, we evaluated the efficacy of the reverse
      less invasive plating system (LISS) in the management of subtrochanteric
      fractures (STF) in elderly patients that are expected to be difficult to nail.
      SUBJECTS AND METHODS: Fifty-five patients with STF were treated from April 2005
      to December 2007. Of these, 26 (16 females and 10 males, age >65 years, average
      79.8 +/- 3) had nonpathologic fractures that were internally fixed with a LISS
      device. The average follow-up period was 24 months (range 15-30). The main
      outcome measures evaluated were pain, union, varus deformity and implant failure.
      Radiographic and clinical evidence of functional outcome and complications were
      also evaluated. RESULTS: Mean perioperative blood loss was 120.5 +/- 12 ml (range
      65-285), and mean postoperative hospital stay was 7.8 +/- 2 days (range 4-14).
      Using the reverse LISS plates led to complete union of STF in all of the 26
      elderly patients without additional procedures. CONCLUSION: Due to advantages
      like high union rate, early postoperative mobilization and short operation time,
      the reverse LISS device offers an alternative management of STF in elderly
      patients unsuitable for nailing procedures.

PMID- 22377911
TI  - Cryopyrin-associated periodic syndrome: a case report and review of the Japanese
      literature.
AB  - Cryopyrin-associated periodic syndrome is an autoinflammatory syndrome caused by
      mutations of the CIAS1 gene (currently named NLRP3), and is characterized by
      periodic attacks of an urticaria-like rash, fever, head-ache, conjunctivitis and
      arthralgia. We report here a case of a 1-year-old boy with cryopyrin-associated
      periodic syndrome, which manifested as a recurrent skin rash in the postnatal
      period. Genetic analysis revealed a missense mutation of the CIAS1 gene in the
      mother and infant.

PMID- 22377912
TI  - Mammalian sialidases: physiological and pathological roles in cellular functions.
AB  - Sialic acids are terminal acidic monosaccharides, which influence the chemical
      and biological features of glycoconjugates. Their removal catalyzed by a
      sialidase modulates various biological processes through change in conformation
      and creation or loss of binding sites of functional molecules. Sialidases exist
      widely in vertebrates and also in a variety of microorganisms. Recent research on
      mammalian sialidases has provided evidence for great importance of these enzymes
      in various cellular functions, including lysosomal catabolism, whereas microbial
      sialidases appear to play roles limited to nutrition and pathogenesis. Four types
      of mammalian sialidases have been identified and characterized to date,
      designated as NEU1, NEU2, NEU3 and NEU4. They are encoded by different genes and
      differ in major subcellular localization and enzymatic properties including
      substrate specificity, and each has been found to play a unique role depending on
      its particular properties. This review is an attempt to concisely summarize
      current knowledge concerning mammalian sialidases, with a special focus on their
      properties and physiological and pathological roles in cellular functions.

PMID- 22377914
TI  - Multiple sclerosis and the Iranian revolution.

PMID- 22377913
TI  - The conserved oligomeric Golgi complex is required for fucosylation of N-glycans
      in Caenorhabditis elegans.
AB  - The conserved oligomeric Golgi complex (COG) is a hetero-octomeric peripheral
      membrane protein required for retrograde vesicular transport and glycoconjugate
      biosynthesis within the Golgi. Mutations in subunits 1, 4, 5, 6, 7 and 8 are the
      basis for a rare inheritable human disease termed congenital disorders of
      glycosylation type-II. Defects to COG complex function result in aberrant
      glycosylation, protein trafficking and Golgi structure. The cellular function of
      the COG complex and its role in protein glycosylation are not completely
      understood. In this study, we report the first detailed structural analysis of N
      glycans from a COG complex-deficient organism. We employed sequential ion trap
      mass spectrometry of permethylated N-glycans to demonstrate that the COG complex
      is essential for the formation of fucose-rich N-glycans, specifically antennae
      fucosylated structures in Caenorhabditis elegans. Our results support the
      supposition that disruption to the COG complex interferes with normal protein
      glycosylation in the medial and/or trans-Golgi.

PMID- 22377915
TI  - Organ transplantation and skin--principles and concepts.
AB  - Solid organ transplantation influences the biology of the skin profoundly. In the
      wake of transplantation, inflammatory, infectious and neoplastic disorders arise,
      often with atypical clinical presentation. Inflammatory disorders mainly relate
      to pathogen-driven conditions such as seborrheic dermatitis and pityrosporum
      folliculitis and to drug reactions. Infectious disorders are dominated by viral
      infections of human papilloma virus and by infections and reactivations of herpes
      family members. Neoplastic disorders are greatly increased with squamous cell
      carcinoma of the skin as most relevant clinical problem which is increased 65- to
      100-fold following transplantation. This dramatic increase in cutaneous
      carcinogenesis results from the isolated effect of ultraviolet light on the skin
      with immunosuppression and DNA damage and of immunosuppressants which drive skin
      cancer formation by properties unrelated to immunosuppression and from the
      combined effect of UV light and immunosuppressive drugs on immunomodulation which
      results in impaired antitumor response as well as chronic tumorigenic
      inflammation.

PMID- 22377916
TI  - Skin problems in immunodeficient patients.
AB  - The most important function of the skin besides social communication is active
      protection against mechanical, chemical and microbial threat. The epidermis has
      biochemical, physical, immunological and anti-infective properties, and is the
      most important shield against aggressors. Chronic immunosuppression impairs this
      cutaneous quality and therefore numerous mucocutaneous complications can occur.
      The physiological colonization of commensal microbes helps to limit the expansion
      of pathogenic bacteria, viruses and fungi by a continuous release of
      antimicrobial peptides from keratinocytes. Genetic or acquired immunodeficiency
      influences these factors. Malignant neoplastic diseases such as leukemia or
      lymphomas can also lead to severe immunodeficiency. Drug-induced immunodeficiency
      is common in organ-transplanted patients with the aim to prevent organ rejection.
      Such patients with prolonged immunodeficiency often develop atypical
      presentations of mucocutaneous infections. This is the reason why such patients
      should be biopsied liberally. In addition to the conventional histology, a part
      of the biopsy should be used for microbiological cultures. Long-term
      complications of oncogenic viruses have to be considered leading to epithelial
      cancers (HPV), Kaposi sarcomas (HHV8), lymphomas (EBV) and Merkel cell tumor
      (polyomavirus) apart from more known acute infections of the skin. Important
      mucocutaneous markers of immunosuppression such as oral hairy leukoplakia, oral
      candidiasis and eczema molluscatum exist. This work reviews the pathophysiology
      of skin protection and describes typical mucocutaneous problems in
      immunosuppressed patients.

PMID- 22377917
TI  - Critical skin cancer in organ transplant recipients--a dermatopathological view.
AB  - Organ transplant recipients (OTR) are at significantly increased risk to develop
      a wide variety of skin cancers, particularly epithelial skin cancer, Merkel cell
      carcinoma and Kaposi's sarcoma. In addition, melanoma, skin adnexal neoplasm and
      cutaneous lymphomas are more common in OTR and may differ in their
      clinicopathological presentation from tumors in immunocompetent patients. The
      accuracy of clinical diagnosis of suspected premalignant and malignant skin
      lesions in OTR is modest. Therefore, histopathological diagnosis is an essential
      element for the diagnostic workup of skin cancers, and additionally provides
      important information on prognosis. This review discusses the histopathological
      aspects of skin cancers in OTR, the impact of dermatopathological analysis on
      prognosis and understanding of the pathogenesis of these neoplasms.

PMID- 22377918
TI  - Immunosuppressive drugs in organ transplant recipients--rationale for critical
      selection.
AB  - Transplantation is the treatment of choice for many different organ failures.
      Despite growing experience in surgery and immunosuppression protocols, the long
      term mortality of the procedure remains much higher than in the general
      population. Second only to cardiovascular diseases as the cause of death in organ
      transplant recipients, cancer is now known to be at least partly related to the
      immunosuppression regimen. Nevertheless, if calcineurin inhibitors have a
      demonstrated pro-oncogenic effect, other classes, such as mTOR inhibitors, are
      antiproliferative, and even demonstrated as an efficient therapy in some advanced
      oncological situations. Therefore, the adaptation of the therapy protocol evolves
      now towards an individualized medicine based on the risk factors of each
      transplant recipient in terms of cardiovascular, infectious and oncological
      diseases. As the first organ involved by tumor is the skin, many different
      guidelines have been published to try and adapt the therapy to the occurrence of
      a new lesion. If, for example, limited actinic keratosis or the first episode of
      a non-melanoma skin cancer usually requires no change of the immunosuppressive
      therapy, but a local specialized care and frequent clinical controls, more
      advanced lesions imply the adaptation of the drug regimen. In any case, the
      collaboration between general practitioners, dermatologists and the
      transplantation team is mandatory.

PMID- 22377919
TI  - Human papillomavirus and squamous cell cancer of the skin--epidermodysplasia
      verruciformis-associated human papillomavirus revisited.
AB  - As squamous cell cancer (SCC) is the most common malignancy in organ transplant
      recipients, a viral etiology has been proposed. Human papillomavirus (HPV) is
      found more often in organ transplant recipients than in the general population,
      but its role in cancer development has been debated for years. As a model of
      susceptibility of HPV the inherited disease epidermodysplasia verruciformis (EV)
      has been investigated intensively. EV is an autosomal-recessive skin disease
      leading to multiple flat warts and pityriasis versicolor-like macules in early
      youth. EV patients are at great risk of developing skin cancer due to a lack of
      defense against beta HPV. Beta HPV are causally involved in the formation of skin
      cancer in patients afflicted with EV. Beta HPV has frequently been detected in
      SCC and its early lesions such as actinic keratoses. Depending on the methods
      used, a prevalence of 30-90% has been reported for beta HPV for SCC in organ
      transplant recipients, while this prevalence in the general population is lower,
      but still considerable at 50%. Epidemiologic studies in the general population
      seem to suggest that beta HPV plays a role in the formation of SCC, both for
      invasive and in situ lesions.

PMID- 22377920
TI  - Pre- and posttransplant management of solid organ transplant recipients: risk
      adjusted follow-up.
AB  - Solid organ transplant recipients (SOTR) have an increased risk of skin cancer
      due to their long-term immunosuppressive state. As the number of these patients
      is increasing, as well as their life expectancy, it is important to discuss the
      screening and management of skin cancer in this group of patients. The role of
      the dermatologist, in collaboration with the transplant team, is important both
      before transplantation, where patients are screened for skin lesions and the
      individual risk for skin cancer development is assessed, and after
      transplantation. Posttransplant management consists of regular dermatological
      consultations (the frequency depends on different factors discussed below), where
      early skin cancer screening and management, as well as patient education on sun
      protective behavior is taught and enforced. Indeed, SOTR are very sensitive to
      sun damage due to their immunosuppressive state, leading to cumulative sun damage
      which results in field cancerization with numerous lesions such as in situ
      squamous cell carcinoma, actinic keratosis and Bowen's disease. These lesions
      should be recognized and treated as early as possible. Therapeutic options
      discussed will involve topical therapy, surgical management, adjustment of the
      patient's immunosuppressive therapy (i.e. reduction of immunosuppression and/or
      switch to mammalian target of rapamycin inhibitors) and chemoprevention with the
      retinoid acitretin, which reduces the recurrence rate of squamous cell carcinoma.
      The dermatological follow-up of SOTR should be integrated into the comprehensive
      posttransplant care.

PMID- 22377922
TI  - History of hematopoietic stem cell transplantation: evolution and perspectives.
AB  - Hematopoietic stem cell transplantation (HSCT) has evolved over the last half
      century from experimental bone marrow transplantation for patients with incurable
      leukemia or bone marrow failure to standard of care for a broad range of patients
      with congenital or acquired disorders of the hematopoietic system or radio-,
      chemo- or immune-sensitive malignancies. More than 60,000 such transplants are
      currently carried out annually worldwide with increasing frequency. HSCT has
      always been closely linked to Dermatology from its very beginning through its
      main and most devastating complication graft-versus-host disease. Treatment
      complications of HSCT have provided a great deal of insight into basic mechanisms
      of immunology, clinical medicine and networking in general. It remains a
      challenge to turn this knowledge from the two disciplines into benefit for the
      future patients with disturbed immune function and skin diseases.

PMID- 22377921
TI  - Future trends in organ transplant recipients--important issues for
      dermatologists.
AB  - It is on the tip of everyone's tongue in the transplant community that recent
      improvements in short-term survival of solid organ allografts have not translated
      into the expected increase in long-term survival. Besides chronic immune-mediated
      damage to the transplanted organ, the poor long-term survival of allografts has
      been attributed to the nephrotoxic effects of the calcineurin inhibitors.
      Moreover, the immunosuppressive burden and metabolic side effects of the current
      anti-rejection drugs are clearly related to increased rates of malignancies,
      infections and accelerated atherosclerosis, all of which make up for the
      premature death of a considerable proportion of transplant recipients with a
      functioning allograft. Therefore, attempts have been made over the last decade to
      either reduce or withdraw both steroids and calcineurin inhibitors from
      maintenance regimens. Furthermore, there is an ongoing intensive search for new
      less toxic and more specific drugs which would ideally selectively impair the
      alloimmune response while preserving the immune system's capacity to fight
      infection and malignancy (i.e. induce tolerance). Moreover, new concepts have
      emerged to individualize a patient's immunosuppressive therapy based on an
      improved pretransplant risk assessment. With the causes of chronic allograft
      damage being increasingly well defined, better and more personalized long-term
      follow-up strategies are being developed to ultimately prevent late allograft
      loss. These aspects will be reviewed here with a focus on kidney transplantation
      and the possible impact of these new approaches on the incidence of skin cancer.

PMID- 22377923
TI  - Acute and chronic skin graft-versus-host disease--pathophysiological aspects.
AB  - Despite impressive advances in the field of allogeneic hematopoietic
      transplantation, graft-versus-host disease (GVHD) remains a significant obstacle
      to overcome. Whereas our understanding of the pathophysiology of acute GVHD has
      greatly improved, so has our knowledge of the complexities of the immune system.
      Much of the immunobiology of GVHD has been gleaned from preclinical models and
      far less from clinical observations or biological studies in human. In this
      chapter, we summarize some of the major advances in GVHD pathophysiology, and the
      potent translation of these from the bench to the bedside.

PMID- 22377924
TI  - Cutaneous graft-versus-host disease--clinical considerations and management.
AB  - Graft-versus-host disease (GVHD) is the primary cause of non-relapse-related
      morbidity and mortality in patients who undergo hematopoietic stem cell
      transplantation. Dermatologic manifestations are common in both acute and chronic
      GVHD. In the acute setting, skin involvement often provides the first indication
      of GVHD and may progress to erythroderma and even skin necrolysis. In the chronic
      phase, skin involvement is extraordinarily polymorphic, potentially involves all
      layers of the skin and subcutaneous tissue, and presents in sclerotic and
      nonsclerotic forms. Management of cutaneous disease is challenging and ideally
      employs a multi-disciplinary approach and an understanding of the multiple
      medical issues facing patients with GVHD. The dermatologist plays a key role in
      caring for the patient with GVHD by providing an accurate diagnosis,
      determination of disease activity and response to treatment, and appropriate
      consideration of all available treatment modalities, including topical, systemic,
      and physical interventions (e.g. phototherapy, extracorporeal photopheresis).
      This chapter describes the cutaneous manifestations of acute and chronic GVHD and
      provides an evidence-based review of current treatment interventions for patients
      with GVHD skin disease.

PMID- 22377925
TI  - UV treatment of chronic skin graft-versus-host disease--focus on UVA1 and
      extracorporeal photopheresis.
AB  - Chronic graft-versus-host disease (GVHD) is a serious and life-threatening
      complication after allogeneic hematopoietic stem cell transplantation. Cutaneous
      manifestations such as lichenoid or sclerotictype skin changes have been
      frequently observed in these patients. UVA1 phototherapy appears as a very
      effective treatment option for treatment-refractory lichenoid and sclerodermatous
      GVHD. Substantial improvements can often be achieved within 8-12 weeks of
      treatment allowing for subsequent reduction or withdrawal of immunosuppressive
      medications. UVA1 treatment acts via a local effect and is therefore only
      indicated for cutaneous manifestations of GVHD. In patients with multiorgan
      involvement by chronic GVHD, extracorporeal photopheresis is an efficacious and
      safe secondline therapy for steroid-refractory disease in both pediatric as well
      as adult patients. Besides high response rates in cutaneous and extracutaneous
      manifestations of chronic GVHD, a substantial corticosteroid-sparing effect and
      improved survival rates have been reported in patients given extracorporeal
      photopheresis treatment.

PMID- 22377926
TI  - Late effects after hematopoietic stem cell transplantation--critical issues.
AB  - Today, long-term prognosis after hematopoietic stem cell transplantation (HSCT)
      has greatly improved. Nevertheless, there are still a number of malignant and
      nonmalignant late effects that can cause substantial morbidity, with considerable
      impact on the health status and quality of life in the long-term survivors.
      Transplant-preparative regimen and graft-versus-host disease are considered the
      main risk factors after allogeneic HSCT. The continuous changes in the
      transplantation practice and in the type of patients selected are responsible
      that the pattern of the late effects after HSCT is changing over time. Relevant
      recent changes concern the avoidance of total body irradiation conditioning
      whenever possible, the higher age of the patients transplanted, the increasing
      use of unrelated donors as well as the introduction of reduced intensity
      conditioning. The detection of an increasing number of late effects should not be
      considered as a drawback of HSCT. The experience gathered during the past decades
      has become the main source of information on which the current management of the
      long-term survivors is based. A broad expertise is mandatory to manage long-term
      survivors. Aftercare of long-term survivors includes a standardized screening,
      counseling of the patients as well as prevention and treatment of late effects.
      Counseling should include self-examination for early cancer detection, and advice
      for healthy lifestyle behavior. Beyond immediate survival, allogeneic HSCT is a
      lifelong commitment between long-term survivors and the transplant team,
      involving the recipient's family and the general health care providers. Proper
      information on 'life after HSCT' should also be provided to the whole community,
      which plays a key role in the social reinsertion of the long-term survivors.

PMID- 22377927
TI  - Drug hypersensitivity reactions during hematopoietic stem cell transplantation.
AB  - Drugs may elicit a considerable variety of clinical signs, often affecting the
      skin and the mucous membranes. The most common are maculopapular exanthema,
      urticaria and angioedema. More rarely pustular, vesiculobullous, vasculitic and
      lichenoid lesions may be observed. Apart from the morphology, also the chronology
      of the occurrence and the evolution of the single skin lesions and the exanthema
      are paramount in the clinical diagnosis. Often, the skin is the only affected
      organ; however, it may herald a systemic involvement of internal organs, such as
      in severe drug-induced hypersensitivity syndromes or anaphylaxis. Cutaneous
      manifestations, particularly maculopapular exanthemas have a high incidence among
      patients treated with hematopoietic stem cell transplantation. In many cases, a
      virus- or drug-induced origin or a combination of both is responsible. However,
      the transplantation itself may also induce similar skin changes. These exanthemas
      include most often graft-versus-host disease, and rarely engraftment syndrome or
      eruption of lymphocyte recovery. The elucidation of the underlying cause of the
      exanthemas occurring in immune compromised patients and the determination of the
      correct diagnosis remain challenging. An extensive differential diagnosis has to
      be put forward. This includes several groups of disorders with sometimes very
      similar cutaneous manifestations. Manifestations form the underlying disease,
      complications from therapy, infections and drug reactions are the most common
      differential diagnoses.

PMID- 22377928
TI  - Future trends in hematopoietic stem cell transplantation.
AB  - The procedure of hematopoietic stem cell transplantation (HSCT) will keep
      expanding over the next decades. The list of indications for autologous or
      allogeneic HSCT of nonmalignant and malignant hematological disorders will grow.
      Other life-threatening diseases such as genetic, metabolic or autoimmune
      disorders including systemic sclerosis will undergo critical evaluation for that
      treatment. As a consequence of continuous research and clinical progress in that
      field, more and more patients will survive HSCT, and physicians will be
      confronted with organ-specific late and very late effects including chronic graft
      versus-host disease (cGVHD). Changes of eligibility criteria for HSCT, quality
      assessment of the stem cell graft, graft manipulation, and new developments in
      donor selection might possibly impact patients' health status and epidemiology as
      well as presentations of posttransplant complications. Efforts to diminish GVHD
      while forcing graft-versus-tumor effects will persist to be one of the major
      goals, and advances in prophylaxis and treatment of cGVHD will remain high
      priority. Changes in stem cell sources and graft manipulation might have
      additional influence on immune reconstitution and posttransplant disorders of
      infectious and immunological type. The recent publications of the National
      Institutes of Health consensus development project on various aspects of chronic
      GVHD has rightly positioned cGVHD as a serious and difficult to treat pleiotropic
      systemic disease with tremendous impact on long-term outcome. In this chapter, we
      will point out some of the most important issues and trends related to HSCT.

PMID- 22377929
TI  - Photoprotection in transplant recipients.
AB  - Skin cancers remain the most commonly diagnosed neoplasms among organ transplant
      recipients (OTRs), comprising nearly 40% of all posttransplant malignancies. The
      occurrence of skin tumors has a considerable impact on the quality of life and
      the overall survival of OTRs. Ultraviolet radiation (UVR) is the major
      environmental cause of nonmelanoma skin cancers, and it is therefore pivotal to
      protect the skin from UVR in order to prevent de novo and progression of
      preinvasive and invasive malignancies. The present chapter delivers background
      information on UVR, photoprotection and accompanying concerns regarding vitamin
      D, as well as educational and behavioral aspects of photoprotection in OTRs; some
      common misconceptions and mistakes regarding photoprotection are addressed as
      well.

PMID- 22377930
TI  - Intestinal temperature, heart rate, and hydration status in multiday trail
      runners.
AB  - OBJECTIVE: To assess heart rate (HR), intestinal body temperature (T(intest)),
      and hydration status changes and relationships in 12 participants in a 3-day
      trail run. DESIGN: Descriptive field study. SETTING: : Three Cranes Challenge
      trail run, in Karkloof, KwaZulu-Natal, South Africa. PARTICIPANTS: Twelve (5 men
      and 7 women) amateur runners. INTERVENTIONS: Trail run of 95 km divided into 3
      stages: elevation gains on the 3 days, 1020, 1226, and 680 m, respectively. MAIN
      OUTCOME MEASURES: Changes in HR, T(intest), serum osmolality, and body mass.
      RESULTS: Environmental conditions were consistently mild (ambient temperature
      range, 11.5-22.8 degrees C; maximum relative humidity range, 95%-97%), average
      running speed varied from 9.00 to 5.14 minutes/km, and distance covered in the 3
      stages ranged from 32 (stages 1 and 3) to 40 km (stage 2). Mean HR ranged from
      134 to 171 beats per minute in the 12 athletes during the trail events and
      averaged at 150 beats per minute, whereas T(intest) ranged between 36.1 and 40.2
      degrees C. The correlation between maximum T(intest) and percent age-predicted
      maximum HR (n = 12) was significant (R = 0.58; P < 0.05), whereas the correlation
      between maximum T(intest) and serum osmolality or body mass did not reach
      significance (R = 0.16, 0.13; P > 0.05). CONCLUSIONS: This study provides
      evidence in support of the contention that maximum T(intest) is more closely
      related to metabolic rate during trail running than percent dehydration. The
      findings do not support an increase in core body temperature with a change in
      serum osmolality or body mass.

PMID- 22377932
TI  - Towards the rational design of foods: the 4th delivery of functionality in
      complex foods conference.

PMID- 22377931
TI  - T-cell-biased immune responses generated by a mucosally targeted adenovirus
      sigma1 vaccine.
AB  - As most pathogens enter through the mucosa, it is important to develop vaccines
      that induce mucosal immunity. To this end, we generated a novel adenovirus (Ad)
      vaccine that displays the sigma1 protein from reovirus to target junctional
      adhesion molecule 1 and sialic acid. Replication-defective Ad5 vectors were
      modified by replacement of the Ad fiber protein with sigma1 (T3Dsigma1) protein
      of reovirus T3D in previous work. Ad5 and Ad5-sigma1 were compared in mouse
      models for gene delivery and vaccination to monitor cytokine, antibody, and T
      cell responses. The viruses were also tested for the ability to transduce and
      mature dendritic cells. Ad5-sigma1 was 40-fold less efficient at gene delivery in
      vivo, yet it was capable of inducing equal or greater cellular immune responses
      and systemic interferon-gamma levels than Ad5 after intranasal administration.
      Despite weaker gross transduction, intranasal administration of Ad5-sigma1
      produced more green fluorescent protein-positive (GFP+) major histocompatibility
      complex class II (MHC II) cells in the draining lymph nodes, less GFP+/MHC II+
      cells in the lungs, and mediated modestly better maturation of dendritic cells in
      vitro. These data suggest that targeting gene-based vaccination via the sigma1
      protein may enhance the T-cell immune response, perhaps by skewing immune
      responses to encoded antigens.

PMID- 22377933
TI  - Five novel locations of Neocentromeres in human: 18q22.1, Xq27.1~27.2, Acro p13,
      Acro p12, and heterochromatin of unknown origin.
AB  - Since the first report in 1993, an ectopic centromere, i.e. neocentromere
      formation, has been reported in more than 100 small supernumerary marker
      chromosomes (sSMC), in 7 instances of centromere repositioning, and in about a
      dozen cases with more complex chromosomal rearrangements. Here we report 2 new
      cases with centromere repositioning and 3 neocentric sSMC consisting exclusively
      of heterochromatic material. Yet, no centromere formation was reported for the
      regions 18q22.1 and Xq27.1~27.2 as it was observed in the 2 cases with centromere
      repositioning here; in both cases, cytogenetically an inversion was suggested.
      Two of the 3 neocentric sSMC were derived from a short arm of an acrocentric
      chromosome. The remainder neocentric sSMC case was previously reported and was
      stainable only by material derived from itself.

PMID- 22377934
TI  - A systematic review of nicotine by inhalation: is there a role for the inhaled
      route?
AB  - INTRODUCTION: A considerable minority of adults remain addicted to smoking
      cigarettes despite substantial education and public health efforts. Nicotine
      replacement therapies have only modest long-term quit rates. The pulmonary route
      of nicotine delivery has advantages over other routes. However, there are
      regulatory and technical barriers to the development of pulmonary nicotine
      delivery devices, and hence, none are commercially available. Current knowledge
      about pulmonary nicotine delivery is scattered throughout the literature and
      other sources such as patent applications. This review draws together what is
      currently known about pulmonary nicotine delivery and identifies potential ways
      that deep lung delivery can be achieved with a simple portable device. AIMS: To
      systematically review clinical trials of nicotine inhalers, determine whether
      they delivered nicotine via the lung, and identify ways that pulmonary delivery
      of medicinal nicotine might be achieved and the technical issues involved.
      METHODS: Systematic search of Medline and Embase. RESULTS: Thirty-eight trials
      met the inclusion criteria. Cough, reflex interruption of smooth inspiration, and
      throat scratch limited the usefulness of nicotine inhalers. The pharmacokinetic
      profiles of portable nicotine inhalers were inferior to smoking, but among
      commercially available products, electronic cigarettes are currently the most
      promising. CONCLUSIONS: Pulmonary nicotine delivery might be maximized by use of
      nicotine salts, which have a more physiological pH than pure nicotine, by
      ensuring the mass of the particles is optimal for alveolar absorption, and by
      adding flavoring agents. Metered-dose inhalers potentially can deliver nicotine
      more efficiently than other nicotine products, facilitating smoking cessation and
      improving smokers' lives.

PMID- 22377935
TI  - "How is smoking handled in your home?": agreement between parental reports on
      home smoking bans in the United States, 1995-2007.
AB  - INTRODUCTION: Home smoking bans significantly reduce secondhand smoke exposure
      among children, but parents may offer discordant reports on whether there is a
      home smoking ban. The purpose of this study was to examine national trends in (a)
      parental discordance/concordance in the reporting of home smoking bans and (b)
      correlates of discordant/concordant reports among two-parent households with
      underage children from 1995 to 2007. METHODS: Data from the 1995/1996, 1998/1999,
      2001/2002, 2003, and 2006/2007 Tobacco Use Supplement of the U.S. Current
      Population Survey were used to estimate prevalence rates and multinomial logistic
      regression models of discordant/concordant parental smoking ban reports by survey
      period. RESULTS: Overall, the percentage of households in which the 2 parents
      gave discordant reports on a complete home smoking ban decreased significantly
      from 12.7% to 2.8% from 1995 to 2007 (p < .001). Compared with households where
      both parents reported a complete smoking ban, discordant reports were more likely
      to be obtained from households with current smokers (p < .01) across survey
      periods. Compared with households where both parents reported the lack of a
      complete home smoking ban, discordant reports were more likely among households
      with college graduates, no current smokers, and parents with Hispanic ethnicity
      (p < .05). CONCLUSIONS: Parental concordance on the existence of a home smoking
      ban increased from 1995 to 2007. This suggests estimates of home smoking bans
      based on just one parent may be more reliable now than they were in the past.
      Interventions to improve the adoption and enforcement of home smoking bans should
      target households with current smoker parents.

PMID- 22377937
TI  - Achilles tendinopathy in club runners.
AB  - Ultrasound (US) changes within the Achilles tendon are present in asymptomatic
      Achilles individuals. We assessed the association of US signs with symptoms of
      Achilles tendinopathy in a study group of club level running athletes and in a
      control group of athletes training at least 2 times per week. The Achilles tendon
      was assessed in its entirety on longitudinal US scans, at the musculotendinous
      junction (MTJ), the calcaneal insertion site, and at a midtendon point. 25 middle
      distance runners, 19 males and 6 females, aged from 18 to 58, were enrolled in
      each group. When compared to control athletes, club level runners presented
      significantly increased tendon thickness (p=0.046) at the musculo-tendinous
      junction, and increased tendon thickness, with no statistical significance, at
      the other landmarks points. Although club level runners were significantly more
      symptomatic and predisposed to develop signs of tendinopathy than control
      athletes (p=<0.001), ultrasound abnormalities were not significantly associated
      with local symptoms complained at the US investigation time. Prospective studies
      on asymptomatic athletes are needed to define the predictive value of US signs of
      Achilles tendinopathy in the development of symptoms in the long-term.

PMID- 22377936
TI  - Recurrent erysipelas secondary to a late prosthetic femoropopliteal bypass
      infection.

PMID- 22377938
TI  - Effects of genu varum deformity on postural stability.
AB  - It is well known that any balance control disturbance can increase the risk of
      injury during sport activities. Knee deformities such as genu valgum and genu
      varum may perturb the line of gravity passing the lower limb joints and so
      disturb dynamic and static balance indices. This study was designed to
      investigate the effects of genu valgum and genu varum deformity on the static and
      dynamic balance indices. 90 non-athletic female university students (age: 21.8+/
      1.75 years, weight: 55.8+/-9.6 kg, height: 161.3+/-11.9 cm) were assigned in one
      of the 3 experimental groups; normal knee (n=30), genu varum (n=30) and genu
      valgum (n=30), according to their knee conditions. Static and dynamic overall
      stability index (OSI), anteroposterior stability index (APSI), mediolateral
      stability index (MLSI) and falling risk were evaluated by the Biodex balance
      system. No significant difference was seen among these groups in terms of dynamic
      and static OSI and APSI, while significantly higher falling risk and lower
      stability was found in the genu varum group compared to the normal groups in term
      of dynamic and static MLSI (p<0.05). The results showed that genu varum deformity
      may increase the normal postural sway in the mediolateral direction and also
      increase falling risk.

PMID- 22377939
TI  - Effect of hyperoxic-supplemented interval training on endurance performance in
      trained cyclists.
AB  - The aim of this study was to determine the effect of hyperoxic-supplemented
      interval training on endurance performance. Using a single-blind, randomised
      control-trial design, 16 well-trained cyclists were randomly assigned to either
      hyperoxic or normoxic training. Participants visited the laboratory twice per
      week, for 4 weeks, to perform high-intensity interval training sessions. A 20 km
      TT, incremental exercise test and 60s all-out test were conducted pre- and post
      intervention. Smaller effects for most physiological measures, including VO 2peak
      (1.9 +/- 4.3%) and lactate threshold (0.3 +/- 8.3%), were observed after training
      in hyperoxia compared to normoxia. There was a small increase in mean power
      during the 20 km TT after hyperoxia [2.1 +/- 3.7%; effect size (ES): - 0.30 +/-
      0.39] but this was less than that observed after normoxia (4.9 +/- 3.9%; ES: -
      0.44 +/- 0.60). During the 60 s all-out test, the peak relative power was
      relatively unchanged, whereas mean relative power was increased in normoxia (2.3
      +/- 3.4%) but not hyperoxia (0.3 +/- 1.2%; ES: - 0.34 +/- 0.49). Hyperoxic
      supplemented interval training in the competitive season had less effect on
      endurance and high-intensity performance and physiology in trained endurance
      cyclists compared to interval training in normoxia. Therefore hyperoxic
      supplemented training at sea level appears to be not worthwhile for maximising
      performance in competitive endurance athletes.

PMID- 22377940
TI  - Force normalization in paraplegics.
AB  - The principal aim of our study was the determination of the effectiveness of a
      standardized ratio, allometric scaling model and a gamma function model in
      normalizing the isometric torque data of spinal cord patients and healthy
      subjects. For this purpose we studied a sample of 21 healthy males and 23 spinal
      cord injury males. The experiment consisted of the measurement of the force of
      the upper limb movement executed by all the subjects. We also determined
      anthropometric variables with dual-energy x-ray absorptiometry. The experimental
      data were analyzed with 3 force normalization methods. Our results indicate that
      the most important confounding variable was the fat free mass of the dominant
      upper limb (r>0.36, p<0.05). With the standardization by body mass and allometric
      scaling model, the normalized torque was influenced by body size variables.
      However, the normalized torque by the gamma function model was independent of
      body size measures. Paraplegics were weaker (p<0.05) in extension movements when
      the data were normalized by the gamma function model. In summary, this study
      shows that the gamma function model with fat free mass of the dominant upper limb
      was more effective than the standardized ratio in removing the influence of body
      size variables.

PMID- 22377941
TI  - Effect of aspirin dose on gastrointestinal permeability.
AB  - The primary purpose of this study was to determine the aspirin dose that
      increases gastrointestinal (GI) permeability. A pilot study was also conducted to
      determine whether the menstrual cycle affects GI permeability. Both portions of
      the study involved 4 experimental conditions. For the aspirin portion, 8 subjects
      ingested 0 mg, 325 mg, 650 mg, or 975 mg of aspirin the night before and the
      morning of an experiment. For the menstrual cycle pilot study, 5 female subjects
      with regular menstrual cycles were tested for GI permeability on the same day
      each week for 4 weeks. GI permeability was assessed by the urinary excretion of
      ingested probes. Sucrose (5 g) was used to determine gastroduodenal permeability.
      Lactulose (5 g) and rhamnose (2 g) were used to assess small intestinal
      permeability via the lactulose-to-rhamnose urinary excretion ratio (L/R). The
      data indicated that the menstrual cycle had no effect on GI permeability. In
      contrast, gastroduodenal permeability was significantly (P <0.008) increased
      following a dose of 650 mg aspirin and small intestinal permeability (L/R) was
      significantly (P <0.008) increased following a dose of 975 mg aspirin. These
      results suggest healthy individuals should be cautious even with acute aspirin
      use as it may result in GI barrier dysfunction.

PMID- 22377942
TI  - Post-exercise cardiac troponin release is related to exercise training history.
AB  - Marathon running can increase circulating cardiac troponin above the diagnostic
      criteria for myocardial infarction. We determined whether prior-exercise
      experience (training history) might be related to the magnitude of immediate post
      race troponin release following completion of the London Marathon in a group of
      non-elite runners. Using a prospective study design, 52 runners were recruited
      into either HIGH T-E (trained-experience) (n=27) or LOW T-E (n=25) groups.
      Cardiac troponin I (cTnI) release following race completion was compared between
      these 2 groups. To examine relationships between cTnI release and participant
      demographic and indices of prior training experience an additional 52 runners who
      did not meet the criteria for either the HIGH T-E or LOW T-E groups were also
      recruited. The combined data from all 104 runners was analysed using multivariate
      linear regression analysis. The results revealed a significant difference in post
      marathon circulating cTnI between LOW T-E runners (median: 0.11 ug/L;
      interquartile range [IQR]: 0.03-0.18 ug/L) and HIGH T-E runners (median: 0.03
      ug/L; IQR 0.02-0.057 ug/L) (p<0.05). Average miles run per week in the last 3
      years, a marker of total training experience, encompassing training volume and
      duration, was negatively associated with post-marathon cTnI release (p<0.001).In
      conclusion, exercise-induced cTnI release is strongly related to previous
      training experience.

PMID- 22377943
TI  - Nitro-oxidative stress biomarkers in active and inactive men.
AB  - Oxidative stress markers are novel factors shown to be related to cardiovascular
      (CVD) risk. We examined the effects of long-term exercise, age, and their
      interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase
      (MPO) levels, all biomarkers of oxidative stress, and determined their
      association with plasma nitric oxide (NOx) levels as an index of NO
      bioavailability. Older (62+/-2 yr) active men (n=12) who had exercised for >30
      years and young (25+/-4 yr) active men (n=7) who had exercised for >3 years were
      age- and BMI-matched to older (n=11) and young (n=8) inactive men. Young subjects
      had lower plasma nitrotyrosine levels than older subjects (P=0.047). Young
      inactive subjects had higher ox-LDL levels than either the young active (P=0.042)
      or the older active (P=0.041) subjects. In addition, plasma oxidative stress
      levels, particularly ox-LDL, were correlated with various conventional plasma
      lipoprotein-lipid levels, and in older subjects were associated with Framingham
      risk score (r=0.49, P=0.015). We found no relationships between plasma oxidative
      stress markers and NOx levels. The findings suggest that a sedentary lifestyle
      may be associated with higher ox-LDL levels and that the levels of oxidative
      stress markers are related to levels of other conventional CVD risk factors and
      overall CVD risk.

PMID- 22377944
TI  - Decreased training volume and increased carbohydrate intake increases oxidized
      LDL levels.
AB  - We studied effects of probiotics and training volume on oxidized LDL lipids (ox
      LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-alpha
      tocopherol, s-gamma-tocopherol, s-retinol, s-beta-carotene and s-ubiquinone-10)
      in marathon runners during 3-months training period, 6-days preparation period
      and marathon run. Runners (n=127) were recruited for a randomized, double-blind
      intervention during which they received either Lactobacillus rhamnosus GG (LGG,
      probiotic group) or placebo drink (placebo group) during whole study. During the
      preparation period, subjects decreased training and increased carbohydrate
      intake. Blood samples were taken at baseline, before 6-days preparation, before
      and immediately after the marathon. Probiotics did not have any effect on ox-LDL,
      s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL
      increased by 28% and 33% during the preparation period and decreased by 16% and
      19% during the marathon run in the placebo and probiotic groups, respectively (in
      all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s
      TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level
      during the preparative period after several months' training suggests that
      aerobic training may reduce the concentration of ox-LDL and that decrease of
      training together with increased energy intake, mainly carbohydrate, before
      marathon is capable of increasing the level of ox-LDL.

PMID- 22377945
TI  - Mitochondrial macrohaplogroup associated with muscle power in healthy adults.
AB  - The present study was undertaken to examine the effect of mitochondrial
      haplogroups on aerobic and anaerobic performance phenotypes such as maximum
      oxygen consumption, muscle power, and muscle mass. We recruited 474 healthy
      Japanese individuals and measured their physical performance phenotypes such as
      peak oxygen uptake, muscle power, and muscle mass. The genotypes for 186
      polymorphisms in the mitochondrial DNA were determined, and the haplotypes were
      classified into 2 macrohaplogroups (i. e., N and M) and 12 haplogroups (i. e., F,
      B, A, N9a, N9b, M7a, M7b, G1, G2, D4a, D4b, and D5). When we compared the 2 major
      Japanese macrohaplogroups, leg extension power (P=0.0395), leg extension power
      based on body weight (P=0.0343), and vertical jump performance (P=0.0485) were
      significantly higher in subjects with mitochondrial macrohaplogroup N than in
      those with macrohaplogroup M. However, peak oxygen uptake was similar between the
      2 groups. When we analyzed the 12 haplogroups, all of the measured parameters
      were similar among them. In conclusion, mitochondrial macrohaplogroup N may be
      one of the determinant factors of anaerobic physical performance phenotype such
      as muscle power.

PMID- 22377946
TI  - Development of a field test for evaluating aerobic fitness.
AB  - The purpose of this study was to investigate the reproducibility and utility of a
      standardised and externally paced field test (15-m Incremental Shuttle Walk and
      Run Test [15 mISWRT]) to assess aerobic fitness in middle-aged adults. 14 middle
      aged participants performed the 15-m ISWRT 3 times within one week (Test 1, Test
      2, Test 3). Reproducibility of the 15-m ISWRT was tested by comparing 15-m ISWRT
      performance (distance completed), HRmax, and VO 2max for each test. The utility
      of the 15-m ISWRT for evaluating VO 2max over a wide range in middle-aged adults
      was tested by comparing the range of VO 2max obtained from the portable expired
      gas analyzer with the VO 2max reference values and ranges for health promotion
      published by Japan's Ministry of Health, Labour and Welfare. A multiple
      comparison of distance completed in the 15-m ISWRT Test 1, Test 2, and Test 3
      found no significant difference between Test 2 and Test 3. The ICC was 0.99 for
      Test 2 vs. Test 3. VO 2max measured from the 15-m ISWRT in Test 3 had a minimum
      value of 22.8 ml/kg/min and a maximum value of 38.7 ml/kg/min. In conclusion, the
      15-m ISWRT is reliable and useful for evaluating VO 2max in middle-aged adults.

PMID- 22377947
TI  - Measuring tactical behaviour in football.
AB  - The present study explored how football players' dynamic positional data can be
      used to assess tactical behaviour by measuring movement patterns and inter-player
      coordination. A pre post-test design was used to assess the effects of a 13-week
      constructivist and cognitivist training program by measuring behaviour in a 5 * 5
      football small-sided game, played on a 60 * 40 m outdoor natural turf pitch. Data
      was captured at 5 Hz by GPS devices (SPI Pro, GPSports, Canberra, Australia) and
      analysed with non-linear signal processing methods. Approximate entropy values
      were lower in post-test situations suggesting that these time series became more
      regular with increasing expertise in football. Relative phase post-test values
      showed frequent periods with a clear trend to moving in anti-phase, as measured
      by players' distance to the centre of the team. These advances may open new
      research topics under the tactical scope and allow narrowing the gap between
      sports sciences and sports coaching.

PMID- 22377948
TI  - Influence of activity patterns in fitness during youth.
AB  - The aim of this study was to analyze longitudinal associations between
      cardiorespiratory fitness, physical activity and body mass index in a 4-year
      longitudinal study. 170 students (97 girls and 73 boys) aged at baseline from 11
      to 17 years were followed. Students performed 20-m-SR; physical activity patterns
      and parents' education were evaluated using a standard questionnaire. Body mass
      index was categorized according to established cut points. In a multilevel
      analysis using MLwIN, 2 level structures were defined: first for individuals and
      second for time observations. In a longitudinal 2 level analysis,
      cardiorespiratory fitness was -negatively associated with body mass index for
      girls and boys, respectively (p<0.05; R2=0.63; 0.62), especially with obesity
      category (p<0.01; R2=0.58; 0.60). In girls, independent associations were
      observed between CRF and PA categories regarding participation "almost every day"
      in organized (p<0.05; R2=0.50) and non-organized sports outside school (p<0.05;
      R2=0.52) and participation in sports competitions (p<0.05; R2=0.51). In boys,
      associations were found only with participation in sports competitions (p<0.05;
      R2=0.50). The results highlight the importance of youth participation in
      organized activities and competitive sports over time to achieve health-related
      fitness benefits.

PMID- 22377949
TI  - Thorax and pelvis kinematics change during sustained cycling.
AB  - The aim of this study was to evaluate time dependent changes in 3 dimensional
      (3D) thorax and pelvis kinematics during an intense 60 min bike ride. 10
      experienced male road cyclists pedalled for 60 min at workloads based on previous
      onset of blood lactate accumulation (OBLA) testing. The 60 min cycle was divided
      into six 10 min periods consisting of 8 min of steady state cycling (88% of OBLA)
      followed by 90 s at 140% of OBLA and a 30 s recovery phase (60% of OBLA). Thorax
      and pelvis kinematic data were recorded from 20 consecutive pedal revolutions
      using a 3D motion capture system (200 Hz) during each steady state phase.
      Repeated measures ANOVA with Bonferroni corrections were used to test for effects
      of test duration on segmental kinematics. Results indicated an effect for test
      duration on the mean thorax (p<0.001) and pelvic tilt (p=0.042), pelvic lateral
      tilt velocity (p=0.006) and the ROM in thoracic lateral tilt (p<0.001). These
      changes all occurred between the 4th and 5th work periods. Findings indicated
      that during the latter stages of a high intensity ride cyclists changed the
      sagittal plane thorax and pelvis orientation, increased lateral thoracic
      movements and pelvic lateral tilt velocities.

PMID- 22377950
TI  - Responses of obese and non-obese boys cycling in the heat.
AB  - This study compared rectal temperature (Tre), heat sensation and sweating between
      obese and non-obese boys during cycling in the heat. Participants (aged 12-15
      years) were 17 obese and 16 non-obese (BMI=29.4+/-4.3 and 16.8+/-1.7 kg . m-2,
      respectively) boys. They cycled for 30-min (50-55% VO(2peak)) in a climatic
      chamber (35 degrees C, 45% RH) and Tre, heat sensation and sweat volume were
      monitored. From the start to the end of cycling, Tre was similar between the
      obese (37.4+/-0.3-37.8+/-0.3 degrees C) and non-obese (37.3+/-0.2-37.9+/-0.2
      degrees C) groups. Heat sensation was higher in the obese group from the start
      (3.6+/-2.7 vs. 1.3+/-1.4 cm; P=0.008) to the end (7.6+/-2 vs. 5.2+/-2.2 cm;
      P=0.003) of cycling. Sweat volume corrected by body surface area was similar
      between the obese (200+/-123 mL . m-2) and non-obese (212+/-80 mL . m-2) groups.
      Initial and final HR were similar in both groups, and RPE was higher in the obese
      group at 25th (P=0.040) and 30th (P=0.019) min. In conclusion, the obese
      pubescent participants presented similar Tre and sweating volume, but higher heat
      sensation while cycling in the heat.

PMID- 22377951
TI  - HBOC attenuates intense exercise-induced cardiac dysfunction.
AB  - The purpose of this study was to investigate whether hemoglobin-based oxygen
      carrier (HBOC) could protect the heart from intense exercise-induced myocardial
      dysfunction. Adult male Sprague-Dawley rats were subjected to 5-h intense
      prolonged running on treadmill with or without HBOC pre-treatment. Immediately
      after exercise, the heart rate (HR) and oxygen delivery capacity of the blood
      were measured. After 1 h of rest, echocardiography was performed to assess the
      post-exercise cardiac function. Then all the hearts were isolated and perfused
      using the Langendorff model for 1 h. Our results proved that pronged exercise
      caused significant LV dysfunction, while HBOC pre-treatment attenuated such a
      damage, as evidenced by the increased oxygen delivery, cardiac fractional
      shortening (FS), rate-pressure product (RPP), +/- dp/dt and coronary flow rate
      (CF) and decreased myocardial necrosis. The releases of cardiac enzymes,
      including creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) were markedly
      reduced. No significant difference of cardiac infarct size was observed among
      groups. In addition, HBOC significantly elevated superoxide dismutase (SOD)
      activity and decreased hydrogen peroxide (H2O2) formation, which indicated the
      exercise-induced cardiac oxidative damage was inhibited. In conclusion, HBOC pre
      treatment showed a promising cardioprotective effect on prolonged exercise
      induced cardiac dysfunction, which was probably associated with its ability to
      decrease myocardium oxidative stress.

PMID- 22377952
TI  - Muscle strength and size balances between reciprocal muscle groups in the thigh
      and lower leg for young men.
AB  - The present study investigated whether the muscle size balance affects the muscle
      strength balance between reciprocal muscle groups in the thigh and lower leg. 18
      young men volunteered as subjects. The joint torques developed during isometric
      maximal voluntary knee extension and flexion, plantar flexion and dorsiflexion
      were measured using a dynamometer. The muscle volumes of knee extensors and
      flexors, plantar flexors and dorsiflexors were determined by magnetic resonance
      imaging. For each of the muscle groups, the joint torque was significantly
      correlated with the muscle volume (r=0.644-0.847) and the y-intercept of the
      regression line between them was not significantly different from zero. Based on
      these observations, the dependencies of muscle strength balance on muscle size
      balance between the knee extensors and flexors and between the plantar flexors
      and dorsiflexors were investigated using the joint torque and muscle volume. The
      correlation between muscle volume ratio and joint torque ratio was significant
      between the plantar flexors and dorsiflexors (r=0.622) but not between the knee
      extensors and flexors (r=0.128). Thus, it is suggested that the strength balance
      is strongly affected by the size balance between the reciprocal muscle groups in
      the lower leg but not in the thigh.

PMID- 22377953
TI  - The reliability of lower extremity and thoracic kinematics at various running
      speeds.
AB  - Whilst various studies have examined lower extremity joint kinematics during
      running, there is limited investigation on joint kinematics at steady-state
      running and at intensities close to exhaustion. Subsequently, the purpose of this
      study was to determine whether the reliability of kinematics in the lower
      extremity and thorax is affected by varying the running speeds during a running
      economy test. 14 trained and moderately trained runners undertook 2 running
      economy tests with each test incorporating 3 intensity stages: 70-, 90- and 110%
      of the second ventilatory threshold, respectively. The participants ran for 10
      min during each of the first 2 stages and to exhaustion during the last stage.
      Kinematics of the ankle, knee, hip, pelvis and thorax were recorded using a 3
      dimensional motion analysis system. Intra-class correlation coefficient (ICC),
      limits of agreement (LOA) and coefficient of variation (CV) were used to
      calculate reliability. The ICC, LOA and CV of the lower extremity and thoracic
      kinematic variables ranged from 0.33-0.97, 1.03-1.39 and 2.0-18.6, respectively.
      Whilst the reliability did vary between the kinematic variables, the majority of
      results showed minimal within-subject variation and moderate to high reliability.
      In conclusion, examining thoracic and lower extremity kinematics is useful in
      determining whether running kinematics is altered with varying running
      intensities.

PMID- 22377954
TI  - 'Gray science'.

PMID- 22377955
TI  - P2X7 receptor modulation of the viability of radial glial clone L2.3 cells during
      hypoxic-ischemic brain injury.
AB  - The purinergic P2X7 receptor (P2X7R) can be activated by ATP and plays
      significant and complex roles in neuropathology. However, research is limited
      concerning the role of P2X7R in radial glia following hypoxia-ischemia (HI). In
      this study, radial glial clone L2.3 cells were cultured and subjected to oxygen
      glucose deprivation (OGD) to generate an HI model in vitro. We found that HI
      decreased P2X7R expression in the L2.3 cells. Activation of P2X7R in L2.3 cells
      by 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) led to cell death in
      a dose- and time-dependent manner, while a P2X7R antagonist, oxidized ATP (oATP),
      alleviated the injury induced by BzATP or HI. We also found that P2X7R modulated
      the phosphorylation of glycogen synthase kinase-3beta (GSK-3beta). The present
      findings suggest that L2.3 cells express P2X7R, and this receptor may be involved
      in HI injury of radial glia by mediating phosphorylation of GSK-3beta.

PMID- 22377957
TI  - Organocatalytic umpolung: N-heterocyclic carbenes and beyond.
AB  - The umpolung strategy encompasses all the methods that make organic molecules
      react in an inverse manner compared to their innate polarity-driven reactivity.
      This concept entered the field of organocatalysis when it was recognized that N
      heterocyclic carbenes (NHCs) can provide catalytic access to acyl anion
      equivalents. Since then, tremendous efforts have followed to develop a broad
      variety of NHC-catalyzed reactions. In addition to this, more recent research
      developments have shown that other families of organocatalysts are also able to
      mediate transformations in which inversion of polarity is involved. This tutorial
      review aims at offering a didactic overview of organocatalytic umpolung and
      should serve as an inspiration for further progress in this field.

PMID- 22377956
TI  - The pathologic characteristics of breast cancer in China and its shift during
      1999-2008: a national-wide multicenter cross-sectional image over 10 years.
AB  - In China, breast cancer is currently the most common malignancy and the sixth
      leading cause of cancer death in women. But, the characteristics of breast cancer
      in the whole population are not determined. The aim of this study was to perform
      a detailed study on pathologic characteristics of breast cancer representing the
      whole population in China during 1999-2008 and to compare the difference in
      invasive breast cancer between the Western and Chinese. We randomly collected
      4,211 inpatient at seven hospitals in representative geographical regions of
      China during 1999-2008. All the hospitals had the ability of comprehensive cancer
      treatment. The pathologic characters including estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
      status were surveyed. The shift of pathologic characters was evaluated and the
      data from China were also compared with those of the Western, both using Chi
      square test. We found as follow. (i) The median age of the patients was 48 years
      and showed the similar characters of Asia. (ii) Breast cancer in China showed
      more invasive ductal carcinoma with larger tumor size, later stage, lower ER and
      PR expression and higher HER2 overexpression than those in the Western (p <
      0.001). (iii) Both tumor size and stage at diagnosis decreased year by year (p <
      0.001). Breast cancer in China showed more aggressive behavior than those in
      western countries, although tumor size and stage at diagnosis decreased by year
      during 1999-2008. We addressed the urgent needs for employ race-specific breast
      cancer screen, diagnosis methods, and therapeutic models in China.

PMID- 22377958
TI  - Noise adjusted principal component reconstruction to optimize infrared
      microspectroscopy of individual live cells.
AB  - We have optimized an imaging methodology capable of monitoring individual live
      HeLa cells using non-synchrotron FTIR in an aqueous environment. This
      methodology, in combination with MATLAB based pre-processing techniques, allows
      fast and efficient collection of data with high signal-to-noise ratio in
      comparison with previous methods using point mode data collection, which required
      manual operation and more collection time. Also, presented are early results that
      illustrate interpretable spectral differences from live cells treated with
      chemotherapeutic drugs, demonstrating the potential of this methodology to
      develop more desirable modes of treatment for patients in their diagnoses and
      treatments for disease.

PMID- 22377959
TI  - Integrative proteomics: perspective in complex system interpretation.

PMID- 22377960
TI  - Sodium imaging of human brain at 7 T with 15-channel array coil.
AB  - Signal-to-noise ratio (SNR) is a major challenge to sodium magnetic resonance
      imaging. Phased array coils have been shown significantly improving SNR in proton
      imaging over volume coils. This study investigates SNR advantage of a 15-channel
      array head coil (birdcage volume coil for transmit/receive and 15-channel array
      insert for receive-only) in sodium imaging at 7 T. Phantoms and healthy human
      brains were scanned on a whole-body 7 T magnetic resonance imaging scanner using
      a customer-developed pulse sequence with the twisted projection imaging
      trajectory. Noise-only images were acquired with blanked radiofrequency
      excitations for noise measurement on a pixel basis. SNR was calculated on the
      root of sum-of-squares images. When compared with the volume coil, the 15-channel
      array produced SNR more than doubled at the periphery and slightly increased at
      the center of the phantoms and human brains. Decorrelation of noise across
      channels of the array coil extended the SNR-doubled region into deep area of the
      brain. The spatial modulation of element sensitivities on the sum-of-squares
      combined image was removed by performing self-calibrated sensitivity encoding
      parallel image reconstruction and uniform image intensity across entire field of
      view was attained. The 15-channel array coil is an efficient tool to
      substantially improve SNR in sodium imaging on human brain.

PMID- 22377962
TI  - Malaria surveillance--United States, 2010.
AB  - PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of
      the genus Plasmodium. These parasites are transmitted by the bite of an infective
      female Anopheles mosquito. The majority of malaria infections in the United
      States occur among persons who have traveled to areas with ongoing malaria
      transmission. In the United States, cases can occur through exposure to infected
      blood products, congenital transmission, or local mosquito-borne transmission.
      Malaria surveillance is conducted to identify episodes of local transmission and
      to guide prevention recommendations for travelers. PERIOD COVERED: This report
      summarizes cases in persons with onset of illness in 2010 and summarizes trends
      during previous years. DESCRIPTION OF SYSTEM: Malaria cases diagnosed by blood
      film, polymerase chain reaction, or rapid diagnostic tests are mandated to be
      reported to local and state health departments by health-care providers or
      laboratory staff. Case investigations are conducted by local and state health
      departments, and reports are transmitted to CDC through the National Malaria
      Surveillance System (NMSS), National Notifiable Diseases Surveillance System
      (NNDSS), or direct CDC consults. Data from these reporting systems serve as the
      basis for this report. RESULTS: CDC received 1,691 reported cases of malaria,
      including 1,688 cases classified as imported, one transfusion-related case, and
      two cryptic cases, with an onset of symptoms in 2010 among persons in the United
      States. The total number of cases represents an increase of 14% from the 1,484
      cases reported for 2009. Plasmodium falciparum, P. vivax, P. malariae, and P.
      ovale were identified in 58%, 19%, 2%, and 2% of cases, respectively. Thirteen
      patients were infected by two or more species. The infecting species was
      unreported or undetermined in 18% of cases. Among the 898 cases in U.S. civilians
      for whom information on chemoprophylaxis use and travel area was known, 45 (5%)
      reported that they had followed and adhered to a chemoprophylactic drug regimen
      recommended by CDC for the areas to which they had traveled. Forty-one cases were
      reported in pregnant women, among whom only two (5%) adhered to chemoprophylaxis.
      Among all reported cases, 176 (10%) were classified as severe infections, of
      which nine were fatal. INTERPRETATION: The number of cases reported in 2010
      marked the largest number of cases reported since 1980. Despite the apparent
      progress in reducing the global burden of malaria, many areas remain malaria
      endemic and the use of appropriate prevention measures by travelers is still
      inadequate. PUBLIC HEALTH ACTIONS: Travelers visiting friends and relatives (VFR)
      continue to be a difficult population to reach with effective malaria prevention
      strategies. Evidence-based prevention strategies that effectively target VFR
      travelers need to be developed and implemented to have a substantial impact on
      the numbers of imported malaria cases in the United States. A large number of
      pregnant travelers diagnosed with malaria did not take any chemoprophylaxis.
      Pregnant women traveling to areas in which malaria is endemic are at higher risk
      for severe malaria and must use appropriate malaria prevention strategies
      including chemoprophylaxis. Malaria prevention recommendations are available
      online (http://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can
      be fatal if not diagnosed and treated promptly with antimalarial medications
      appropriate for the patient's age and medical history, the likely country of
      malaria acquisition, and previous use of antimalarial chemoprophylaxis.
      Clinicians should consult the CDC Guidelines for Treatment of Malaria and contact
      the CDC's Malaria Hotline for case management advice, when needed. Malaria
      treatment recommendations can be obtained online
      (http://www.cdc.gov/malaria/diagnosis_treatment) or by calling the Malaria
      Hotline (770-488-7788 or toll-free at 855-856-4713).

PMID- 22377963
TI  - Inhibitory effects of GHRH antagonists on human GH-secreting adenoma tissue.
AB  - Experimental data indicate that antagonists of growth hormone-releasing hormone
      (GHRH) could be used clinically in disorders characterized by excessive
      GHRH/growth hormone (GH) secretion, but direct evidence for the effectiveness of
      GHRH antagonists on human pituitary tissue is still lacking. In this study, we
      investigated the inhibitory effect of our GHRH antagonists MZ-4-71 and JV-1-36
      and the somatostatin (SST) analog RC-160 on superfused pituitary cells obtained
      from a human GH-secreting adenoma. Using Western blot analysis and
      immunohistochemistry, we demonstrated profuse expression of the GHRH receptor and
      its major splice variant SV1 and an increase in the expression of Gsa protein in
      the adenoma tissue. Exposure of the tumor cells to exogenous pulses of GHRH
      induced definite GH responses, causing a 3- to 5-fold elevation of the basal GH
      level. The antagonists MZ-4-71 and JV-1-36 did not alter basal GH secretion,
      indicating that the adenoma cells did not secrete GHRH in an autocrine manner.
      However, both antagonists prevented the stimulatory effect of exogenous GHRH.
      Similarly to the GHRH antagonists, neither SST-14 nor the SST analog RC-160 had
      an effect on the basal GH secretion of the tumor cells, but both peptides
      inhibited the stimulatory effect of exogenous GHRH, with RC-160 being more potent
      than SST. Our study provides direct evidence for the effectiveness of potent GHRH
      antagonists such as MZ-4-71 and JV-1-36 on human pituitary GH-secreting adenoma
      tissue and strongly suggests that these drugs could be used for therapy of GHRH
      associated forms of acromegaly, particularly for those patients in whom surgery
      fails or is not an option.

PMID- 22377964
TI  - Intrinsic catalytic role of mesoporous silica in preferential oxidation of carbon
      monoxide in excess hydrogen.
AB  - We have studied the intrinsic catalytic role of MCM-41 mesoporous silica in
      preferential oxidation of CO in excess H(2) (PROX). Two types of MCM-41 supports
      (MCM-41A and MCM-41B) were obtained from the same pristine as-synthesized
      materials by using different procedures for surfactant removal: one-step
      calcination or two-step extraction-calcination. Although two kinds of Pt
      catalysts prepared from the MCM-41 supports exhibit high similarity in apparent
      physicochemical parameters such as Pt morphology, particle-size distribution,
      electronic states, support architecture, and pore-size distribution, they show a
      dramatic difference in catalytic activity (ca. 100 % versus 10 % CO conversions
      at 298 K). This feature motivated us to investigate the catalytic role of MCM-41
      in the PROX reaction. By means of infrared experiments with the isotope tracer
      technique, it was revealed that the reactive microenvironment at the interface
      between Pt and the MCM-41A support is the origin of the high activity. On the
      highly active Pt/MCM-41A catalyst, interfacial silanols play a decisive role in
      the ignition of CO oxidation, and gaseous O(2) and H(2) are dissociated on CO
      free Pt sites created by the interfacial reaction. The dissociated oxygen and
      hydrogen are proposed to sustain the catalytic cycle in the form of regenerated
      silanols on the support, which is catalyzed by the Pt surface in the presence of
      H(2).

PMID- 22377965
TI  - Influence of mindfulness practice on cortisol and sleep in long-term and short
      term meditators.
AB  - BACKGROUND: There is growing scientific interest in assessing the biological
      correlates of non-pharmacological interventions such as mindfulness. Examinations
      of the beneficial effects of mindfulness on hypothalamus-pituitary-adrenocortical
      system activity (HPA SA) and sleep are sparse. The aim of the present study was
      to explore the impact of long- and short-term meditation experience on HPA SA and
      sleep. METHOD: There were 20 participants, 9 of whom had long-term experience in
      meditation (mean = 264 months) and 11 novices. Novices underwent an 8-week course
      in Mindfulness-Based Stress Reduction (MBSR), and cortisol samples were taken in
      the lab at the beginning and end of the course. To assess the cortisol awakening
      response, 4 morning cortisol samples were collected. Sleep and mindfulness were
      assessed by self-rating questionnaires. RESULTS: Among participants with long
      term meditation experience, morning cortisol decreased with length of experience.
      For novices, after an 8-week introductory MBSR course, morning cortisol levels
      had decreased, while both sleep and self-attribution of mindfulness significantly
      improved. Cortisol levels did not, however, change between the beginning and end
      of individual MBSR sessions. CONCLUSIONS: The pattern of results lends support to
      the view that MBSR/meditation has a favorable influence both on biomarkers of
      stress regulation, such as cortisol secretion, and on sleep.

PMID- 22377966
TI  - Elevated enolase and caveolin-1 in the heart of rats following dexamethasone
      induced toxicity.
AB  - Dexamethasone (DEX)-induced heart damage is associated with enzyme and protein
      alterations. The purpose of this study was to investigate DEX-induced alterations
      in cardiac enolase and caveolin-1 (cav-1) following DEX administration. Male
      Wistar rats were randomly divided into two groups: a control and a DEX. The DEX
      group intraperitoneally received DEX at the single dose of 10 mg/kg for 7
      consecutive days, and the control was given the same amount of saline via the
      same route. On day 8, the rats were anesthetized, and a thoracotomy was performed
      in all animals. Immunohistochemical analysis was performed to evaluate protein
      expression of enolase and cav-1. Sections were analyzed by digital image
      analysis. Our results demonstrated that cardiac protein expression of enolase and
      cav-1 was altered following DEX-induced toxicity in the rat. The expression of
      enolase and cav-1 was significantly increased after DEX treatment, supported by
      integrated optical density compared with the control (P<0.05). In conclusion,
      following DEX-induced toxicity, protein expression of enolase and cav-1 was
      significantly elevated. The current findings indicate that such alterations would
      be reflected in abnormal cardiac function, and the proteins identified in this
      study may be useful in revealing the mechanisms underlying DEX-induced toxicity
      and also in providing various clues for further research.

PMID- 22377967
TI  - Risk of ventricular arrhythmias after myocardial infarction with diabetes
      associated with sympathetic neural remodeling in rabbits.
AB  - BACKGROUND: Abnormal sympathetic innervation underlies both long-term
      hyperglycemia and myocardial infarction (MI). The incidence of ventricular
      arrhythmias (VAs) after MI is higher in diabetic than in nondiabetic patients.
      However, the exact mechanism remains unclear. In this study, we aimed to explore
      sympathetic neural remodeling after MI in diabetic rabbits and its relationship
      with VAs. METHODS: Rabbits were randomly assigned to 4 groups: control, diabetes
      mellitus (DM), MI and diabetic myocardial infarction (DI). After
      electrophysiological experiments in vivo, immunohistochemistry and real-time RT
      PCR were used to measure sympathetic innervations. To test the function of
      sympathetic nerve fibers, norepinephrine levels were measured by high-performance
      liquid chromatography. RESULTS: The corrected QT interval and QT dispersion were
      significantly more prolonged with DI than other conditions. The density of
      tyrosine hydroxylase-positive fibers and corresponding mRNA abundance was
      significantly higher with DI than with DM and under control conditions, but was
      lower than with the MI group. Moreover, the distribution and structure of
      regenerated nerve was heterogeneous in DI rabbits. Norepinephrine content was
      higher in the DI group, and accompanied by an increased quantity of tyrosine
      hydroxylase-positive fibers. CONCLUSION: MI results in sympathetic neural
      remodeling in diabetic rabbits, which may be responsible in part for the
      increased occurrence of VAs.

PMID- 22377968
TI  - p38alpha MAPK mediates 17beta-estradiol inhibition of MMP-2 and -9 expression and
      cell migration in human lovo colon cancer cells.
AB  - Epidemiological studies demonstrate that the incidence and mortality rates of
      colorectal cancer in women are lower than in men. However, it is unknown if
      17beta-estradiol (E(2)) treatment is sufficient to inhibit cell proliferation and
      cell migration in human colon cancer cells. Up-regulation of urokinase
      plasminogen activator (uPA), tissue plasminogen activator (tPA), and matrix
      metallopeptidases (MMPs) is reported to associate with the development of cancer
      cell mobility, metastasis, and subsequent malignant tumor. In the present study,
      we treated human LoVo colon cancer cells with E(2) to explore whether E(2) down
      regulates cell proliferation and migration, and to identify the precise molecular
      and cellular mechanisms behind the down-regulatory responses. Here, we found that
      E(2) treatment decreased cell proliferation and cell cycle-regulating factors
      such as cyclin A, cyclin D1 and cyclin E. At the same time, E(2) significantly
      inhibited cell migration and migration-related factors such as uPA, tPA, MMP-2,
      and MMP-9. However, E(2) treatment showed no effects on upregulating expression
      of plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of
      metalloproteinase-1, -2, -3, and -4 (TIMP-1, -2, -3, and -4). After
      administration of inhibitors including QNZ (NFkappaB inhibitor), LY294002 (Akt
      activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor) or
      SP600125 (JNK1/2 inhibitor), E(2) -downregulated cell migration and expression of
      MMP-2 and MMP-9 in LoVo cells is markedly inhibited only by p38 MAPK inhibitors,
      SB203580. Application of specific target gene siRNA (ERalpha, ERbeta, p38alpha,
      and p38beta) to LoVo cells further confirmed that p38 MAPK mediates E(2) /ERs
      inhibition of MMP-2 and -9 expression and cell motility in LoVo cells.
      Collectively, these results suggest that E(2) treatment down-regulates cell
      proliferation by modulating the expression of cyclin A, cyclin D1 and cyclin E.
      E(2) treatment simultaneously impaired cell migration by inhibiting the
      expression of uPA, tPA, MMP-2, and MMP-9 through E(2) /ERs - p38alpha MAPK
      signaling pathway in human LoVo colon cancer cells.

PMID- 22377969
TI  - Treatment of severe acne with low-dose isotretinoin.

PMID- 22377971
TI  - Protein expression of estrogen receptors alpha and beta and aromatase in
      myometrium and uterine leiomyoma.
AB  - BACKGROUND: Leiomyomas are the most common tumors of the female reproductive
      tract and a major public health problem. The mechanism of tumorigenesis is
      unknown, but evidence suggests that estrogens regulate cell proliferation and
      myoma growth. This effect might be due to different amounts of estrogen receptors
      (ERalpha and ERbeta) in normal and myoma tissues and overexpression of aromatase
      P450 in myomas. PURPOSE: To assess protein expression of ERs and aromatase in
      leiomyomas and normal adjacent myometrium of premenopausal women. METHODS:
      Samples were collected from 12 premenopausal women admitted for abdominal
      hysterectomy due to fibroids. RESULTS: The protein expression of ERalpha, ERbeta
      and aromatase was similar in leiomyoma and normal myometrium (p = 0.239, p =
      0.695 and p = 0.203, respectively). CONCLUSIONS: In this analysis of 12 matched
      leiomyoma and myometrial samples, the data do not support the theory that
      overexpression ERalpha, ERbeta and aromatase in uterine leiomyomas compared to
      adjacent myometrium are the cause of tumor growth. The estrogens may exert their
      growth-stimulatory effects on leiomyomas intermediated by other elements, such as
      cytokines and growth or apoptosis factors. The effect of estrogen on the growth
      and development of fibroids is complex and far from being completely understood.

PMID- 22377972
TI  - Chromosome analysis of 82 species of Scarabaeoidea (Coleoptera), with special
      focus on NOR localization.
AB  - The aim of this study was the identification of the ancestral location of the
      nucleolus organizer region (NOR) in the Scarabaeoidea superfamily, and its
      evolutive trends in the karyotypes. For this purpose, the mitotic and meiotic
      chromosomes at pachynema of 82 species belonging to 4 families and 8 subfamilies,
      including 49 species without any published data, were examined after Giemsa
      staining, C-banding and NOR staining. It could be perceived that most karyotypes
      are composed of 18 nonacrocentric autosomes, an acrocentric X and a punctiform Y.
      NORs are frequently located on the X independent of its morphology. In contrast,
      autosomal NORs are frequently on the rare acrocentric short arms. Thus, it could
      be shown that the ancestral karyotype was very probably composed of 18
      metacentric/submetacentric autosomes, an NOR carrier acrocentric X and a
      punctiform Y. The NOR translocation on autosomes parallels the passage to their
      acrocentric morphology. It is proposed that the frequent location of the NOR on
      the X of beetles, and possibly other insects, is made possible by their mode of
      dosage compensation of the X chromosome, consisting in the overexpression of the
      unique X of the males.

PMID- 22377973
TI  - Pharmacokinetics and pharmacodynamics of gastroretentive delivery of
      levodopa/carbidopa in patients with Parkinson disease.
AB  - OBJECTIVE: To investigate, in patients with Parkinson disease, the
      pharmacokinetics and pharmacodynamics of levodopa/carbidopa delivered via 3
      different extended-release (ER) tablet formulations. METHODS: This was a
      randomized, crossover study in patients with stable idiopathic Parkinson disease
      comparing a conventional ER tablet (C-ER) administered orally 3 times daily with
      2 levodopa/carbidopa gastroretentive ER formulations administered orally twice
      daily, one with an immediate release (IR) component (IR/ER) and one without (ER).
      Blood samples were collected for pharmacokinetic (PK) analysis, and a finger
      tapping test was performed to assess pharmacodynamics. Tolerability was evaluated
      by monitoring adverse events and measuring vital signs. PK modeling was performed
      to estimate steady-state levodopa concentrations. RESULTS: Fourteen patients
      completed the study. Compared with C-ER, both gastroretentive ER tablets
      significantly extended the first maximum time (6.0 vs 2.5 h; P < 0.025) and had
      smoother plasma concentration-time profiles while achieving a similar maximum
      plasma concentration and area under the curve. The IR/ER formulation exhibited a
      significantly longer duration of concentration above the presumed efficacious
      threshold of 300 ng/mL (21 vs 18 h; P = 0.0027) compared with C-ER. PK modeling
      predicts a steady-state levodopa peak/trough ratio of 4 for both IR/ER and ER
      formulations and a ratio of 21 for C-ER. Furthermore, superior response in the
      finger tapping test was observed for the IR/ER and ER formulations compared with
      the C-ER formulation. CONCLUSIONS: This study demonstrated that the
      gastroretentive ER formulations achieved more constant plasma levodopa
      concentrations and better pharmacodynamics with reduced dose frequency,
      potentially reducing the on-off phenomena that have been associated with
      fluctuations in plasma levodopa concentrations.

PMID- 22377974
TI  - Using Google Analytics as a process evaluation method for Internet-delivered
      interventions: an example on sexual health.
AB  - The study aimed to demonstrate the potential of Google Analytics as a process
      evaluation method for Internet-delivered interventions, using a website about
      sexual health as an example. This study reports visitors' behavior until 21
      months after the release of the website (March 2009-December 2010). In total,
      there were 850 895 visitors with an average total visiting time (i.e. dose) of
      5:07 min. Google Analytics provided data to answer three key questions in terms
      of process evaluation of an Internet-delivered intervention: (i) How do visitors
      behave?; (ii) Where do visitors come from? and (iii) What content are visitors
      exposed to? This real-life example demonstrated the potential of Google Analytics
      as a method to be used in a process evaluation of Internet-delivered
      interventions. This is highly relevant given the current expansion of these
      interventions within the field of health promotion.

PMID- 22377975
TI  - Microcystin-LR and chemically degraded microcystin-LR electrochemical oxidation.
AB  - Microcystins (MCs) are cyclic hepatotoxic heptapeptides produced by certain
      strains of freshwater cyanobacteria toxic for humans and animals. The
      electrochemical behaviour of microcystin-LR (MC-LR) at a glassy carbon electrode
      (GCE) was investigated using cyclic voltammetry (CV), square wave voltammetry
      (SWV) and differential pulse voltammetry (DPV). The oxidation of MC-LR is a
      diffusion-controlled irreversible and pH-independent process that occurs with the
      transfer of only one electron and does not involve the formation of any
      electroactive oxidation product. Upon incubation in different pH electrolytes,
      homogeneous degradation of MC-LR in solution was electrochemically detected by
      the appearance of a new oxidation peak at a lower potential. The electrochemical
      behaviour of chemically degraded MC-LR is an irreversible, pH-dependent process,
      and involves the formation of two redox products that undergo reversible
      oxidation. The formation of degradation products of MC-LR was confirmed by HPLC
      with UV detection at room temperature. Experiments were also carried out in
      solutions containing constituent MC-LR amino acids, which enabled the
      understanding of the MC-LR electron transfer reaction and degradation. An
      oxidation mechanism for MC-LR is proposed.

PMID- 22377976
TI  - [Diagnostic assessment of a pulmonary coin lesions with the example of a young
      patient].

PMID- 22377977
TI  - [Methylphenidate misuse].
AB  - Methylphenidate (MPH) is mainly used for treatment of the attention-deficit
      hyperactivity syndrome (ADHS). Non-medical use of methylphenidate as recreational
      drug or performance enhancer has increased in recent years. Methylphenidate is
      also misused in combination with other drugs. Patients with ADHD are also at risk
      to misuse their prescribed methylphenidate medication. Oral and nasal abuse of
      methylphenidate is most common and is in general associated with minor or
      moderate sympathomimetic toxicity. In contrast, severe toxicity has been reported
      for both intravenous and intraarterial administration of crushed methylphenidate
      tablets.

PMID- 22377978
TI  - [How to assess the nutritional status of my patient].
AB  - Protein-energy-malnutrition is a growing problem in industrialised countries.
      Many studies have found malnourishment in 20-60% of hospitalized medical or
      surgical patients, as well as out-patients. Malnutrition negatively influences
      patients' prognosis, immune system, muscle strength, and quality of life. As it
      is a largely treatable co-morbidity, systematic screening for malnutrition and
      effective management will improve patient outcomes and reduce healthcare costs.
      Early diagnosis and assessment depends on a simple and standardised screening
      tool that identifies at-risk patients, allowing the medical team in charge to
      solve patients' nutritional problems with an interdisciplinary approach.

PMID- 22377979
TI  - [Traumatic brain injury in children].
AB  - The general practitioner has an important role in the acute management and during
      the rehabilitation process of children after a traumatic head injury. Latest
      research shows that sequelae may occur even after a mild head injury without loss
      of consciousness. Recognizing the warning signs and symptoms after a head injury
      allows the general practitioner to counsel the child and parents in secondary
      prevention, particularly in order to avoid any further head injury during the
      recovery phase. Under the supervision of the general practitioner, a gradual
      progressive return to the child's everyday activities optimizes the chances of a
      rapid and complete recovery.

PMID- 22377980
TI  - [Diagnostics in recurrent angioedema].

PMID- 22377981
TI  - [Heartburn: in short-term treatment you have the choice!].

PMID- 22377982
TI  - [Rheumatic symptoms in a malignant disease].
AB  - We report a case of a 75 year old women with increasing deterioration of her
      general condition. We found a massive lymphadenopathy, an impressive exanthem and
      an elevation in leukocytes. After conducting a lymphnodebiopsy the diagnosis of
      an angioimmunoblastic T-Cell-Lymphoma was confirmed. Even with chemotherapy
      containing antracycline the prognosis of this disease is very poor. However this
      therapy couldn't be initiated because of the weak condition of the patient. She
      died a few days after hospitalisation.

PMID- 22377983
TI  - [A case of complex discharge medication].
AB  - At discharge of a 72 year old epileptic patient from the hospital, the clinician
      prescribed the switch from Orfiril(r) to Lamictal(r). The general practitioner
      misinterpreted the confusing medication list and made handwritten changes. Later
      on, family members of the patient observed a discrepancy between the handwritten
      comments of the general practitioner and the medication list of the clinician.
      The medication could be re-evaluated in cooperation with the hospital pharmacy
      and the general practitioner. An early interdisciplinary collaboration would help
      improving patient safety.

PMID- 22377984
TI  - [Insomnia: simple behavior therapy improves sleep].

PMID- 22377985
TI  - [Quinine is effective in prevention of muscle cramps].

PMID- 22377990
TI  - Construction of 0D to 3D cadmium complexes from different pyridyl diimide
      ligands.
AB  - Four semirigid ditopic ligands, N,N'-bis(3-pyridylmethyl)-pyromellitic diimide
      (L(1)), N,N'-bis(4-pyridylmethyl)-pyromellitic diimide (L(2)), N,N'-bis(3
      pyridylmethyl)-naphthalene diimide (L(3)), and N,N'-bis(4-pyridylmethyl)
      naphthalene diimide (L(4)), reacted with Cd(NO(3))(2) to result in four
      cadmium(II) complexes, namely, {[Cd(2)(L(1))(2)(NO(3))(4)(CH(3)OH)(4)].H(2)O}
      (1),
      [Cd(L(2))(NO(3))(2)(CH(3)OH)(2).Cd(2)(L(2))(3)(NO(3))(4)].{4(HCCl(3)).2H(2)O}(n)
      (2), {[Cd(L(3))(2)(NO(3))(2)]}(n) (3), and
      {[Cd(L(4))(2)(NO(3))(2)].2(CHCl(3))}(n) (4). These complexes have been
      characterized by elemental analyses, powder X-ray diffraction, thermogravimetric
      (TG) analyses, IR spectroscopy, and single-crystal X-ray diffraction. Structural
      analyses show that four types of structures are formed: (1) a discrete M(2)L(2)
      ring with two Cd ions and two cis-L(1) ligands comprising a zero-dimensional
      molecular rectangle (0D), (2) an unusual zigzag linear chain and a one
      dimensional ladder existing simultaneously in the crystal lattice (1D), (3) a two
      dimensional network of the (4,4) net structure (2D), and (4) an unusual chiral
      three-dimensional framework with 5-fold interpenetrating diamond (dia) topology
      (3D). In these complexes, the ligands exhibit different coordination modes and
      construct various architectures by bridging Cd(NO(3))(2) inorganic building
      blocks. These results suggest that structural diversity of the complexes is
      tunable by ligand modifications, that is, varying the ligand spacer bulkiness or
      substituent position of terminal group. Furthermore, gas adsorption measurements
      indicate that 4 possesses moderate CO(2) uptake and some adsorption selectivity
      for CO(2) over N(2).

PMID- 22377991
TI  - Radial distribution modeling of liquid-phase phenol concentration in a liquid
      solid fluidized bed photoreactor.
AB  - A fluidized bed photoreactor with titanium dioxide-immobilized spherical
      activated carbon particles was examined. The light intensity profile was modeled
      using the Lambert-Beer rule for the modeling of the radial distribution of liquid
      phase phenol concentration in the fluidized bed photoreactor, when considering
      the reactor composed of numerous differential annular drums and no mass transfer
      between drums. The model could be well matched with the experimental data which
      indicated the liquid flow rate of 13.8 L/min was the optimum in the balance of
      flow rate-related light penetration and photocatalyst concentration. By
      integration of liquid-phase phenol concentration along the radius, photocatalytic
      oxidation performance of the photoreactor was evaluated in comparison with the
      experimental data and model prediction. The results showed that the errors were
      less than 30% for most of the predictions. It is suggested that mass transfer and
      flow rate difference along the radial direction should be considered to obtain
      more precise prediction.

PMID- 22377992
TI  - Use of a stable carbon isotope to assess the efficiency of a drinking water
      treatment method with CO2.
AB  - CO2 gas with a special isotopic signature (delta13C = -35.20/00 vs. VPDB) was
      used as a marker to evaluate the efficiency of a drinking water treatment method
      and the effect of an ultrasonic (US) stirrer. This treatment was developed to
      prevent precipitation and corrosion effects in water-supply systems. The research
      work was performed using a laboratory-scale pilot plant that was filled with tap
      water. The stable isotope analyses of delta13C-DIC (Dissolved Inorganic Carbon)
      in the water samples indicated that the maximum content of added CO2 gas in DIC
      was in the range of 35 to 45%. The use of the US stirrer during the entire
      experiment decreased the method's overall efficiency by 10%, due to degassing at
      a late stage of the experiment but accelerated the dissolution process in the
      early experimental stage.

PMID- 22377993
TI  - Evaluation of DNA isolation procedures for detecting and quantifying
      environmental Legionella by real-time quantitative PCR.
AB  - Six methods, QiAamp DNA Mini Kit (Q), Q with Sepharose 4B gel column (Q/G), Q
      with low melting point agarose (Q/L), freeze-thaw/phenol-chloroform lysis (FT
      PC), FT-PC/G, and FT-PC/L, were evaluated for their ability to isolate DNA of
      sufficient quality to quantify Legionella using qPCR. Samples of mixing
      Legionella pneumophila (ATCC33152) and humic acid (HA, 0-126.8 mg/l) were treated
      by the six methods. Q, Q/G, Q/L, FT-PC/G, and FT-PC/L removed HA from 1.9-126.8
      to <1 mg/l determined by A260 with a spectrophotometer. Q obtained the highest
      DNA yield, followed by Q/G. Dilution (10- to 100-fold) of DNA arising from
      extraction using Q, Q/G, FT-PC, or FT-PC/G prevented qPCR inhibition. The highest
      recovery of cells was found in DNA extracted by Q and diluted 100-fold, and
      followed by Q/G. The applicability of Q and Q/G with dilution was further
      validated with cooling tower waters. Q or Q/G with 10-fold dilution increased L.
      pneumophila detection, whereas 100-fold dilution obtained the highest cell
      concentrations. Similar results were found for Legionella spp. except that both
      10- and 100-fold dilutions increased cell concentrations. Thus, Q with 10-fold
      dilution is suggested to detect and quantify Legionella spp. and detect L.
      pneumophila. For L. pneumophila-positive samples, 100-fold diluted DNA must be re
      analyzed to accurately quantify L. pneumophila.

PMID- 22377994
TI  - The organic contamination survey and health risk assessment of 16 source water
      reservoirs in Haihe River basin.
AB  - Although contamination by organic pollutants has previously been reported to
      occur in the Haihe River basin, few studies have been carried out on the levels
      of source water reservoir contamination and the health risk in the Haihe River
      basin. To understand the organic pollution status of the reservoirs in the Haihe
      River basin, samples were collected from 16 source water reservoirs. The samples
      were analyzed for the representative organic pollutants, which included benzene
      homologues, chlorobenzene compounds, organophosphorus pesticides, and
      nitrobenzene compounds, a total in all of 17 compounds. It was observed that the
      concentrations of the 17 compounds in the 16 reservoirs were all less than the
      limit laid down by Chinese surface water quality standards. In addition, benzene,
      toluene, nitrobenzene, p-nitrochlorobenzene, 2,4-dinitrotoluene and 2,4
      dinitrochlorobenzene, dichlorvos, demeton, dimethoate methyl parathion, malathion
      and parathion were frequently detected in the 16 source water reservoirs,
      especially the organophosphorus pesticides; the detection rates of dichlorvos,
      dimethoate, methyl parathion, malathion and parathion were all 100% in the 16
      source water reservoirs. The detection rate of target compounds suggested that
      organic pollution had been common in the source water of the Haihe River basin.
      The health risk assessment results suggested that the noncarcinogenic risk hazard
      quotient values of the target compounds were less than one, and the cancer risk
      values were all below 1 * 10(-6), which indicated that the heath risk produced by
      the target compounds in the 16 reservoirs was at an acceptable level.

PMID- 22377995
TI  - Computational simulation of flocculent sedimentation based on experimental
      results.
AB  - Computerised interpolation algorithms as well as the empirical model for
      analysing the flocculent settling data were developed. A mechanistic semi
      empirical model developed from fundamental physical principles of a falling
      particle in a viscous fluid was tested against actual flocculation column data.
      The accuracy of the mechanistic model was evaluated using the sum of the squared
      errors between the interpolated values (real values) and the model predictions.
      Its fitting capabilities were compared with Ozer's model using nine flocculent
      data sets of which four were obtained from literature and the rest were actual
      data from the performed experiments. The developed model consistently simulated
      the flocculation behaviour of particles in settling columns better than Ozer's
      model in eight of the nine data sets considered. It is recommended that the
      model's performance be further compared with other models like the Rule based and
      San's model. The errors due to the use of interpolated values when determining
      the performance of the empirical models need to be investigated. Furthermore, a
      three-way rather than two-way interpolation should now be achievable using the
      interpolation algorithm developed in this study thereby reducing the effects of
      interpolation bias. The above work opens the way to full automation of design of
      flocculation sedimentation basins and other gravitational particle separation
      systems which at present are designed manually and are susceptible to a wide
      range of human and random errors.

PMID- 22377996
TI  - Modelling of ionic interactions with wastewater treatment biomass.
AB  - Titration data for samples of mixed salts with glycine, baker's yeast cell mass
      and anaerobic digester sludge were obtained and compared to a speciation model of
      weak acid-base interaction in aqueous solutions. The effect of glycine on the
      buffer intensity of the solution could be precisely described by the speciation
      model but did not represent the proton exchange characteristics of either baker's
      yeast or anaerobic sludge well. A model component, UKZiNe, consisting of
      carboxylic acids, phosphate and amine groups described the baker's yeast well,
      and a combination of UKZiNe and carbonate-yielding inorganic solids described
      anaerobic digester sludge. The effect of biomass on buffer intensity in the pH
      range 6.5 to 8 was small for the concentration ranges tested.

PMID- 22377997
TI  - Influence of surface modification of polyethylene biocarriers on biofilm
      properties and wastewater treatment efficiency in moving-bed biofilm reactors.
AB  - Two methods of surface modification of polyethylene biocarriers, chemical
      oxidation-surface covering with ferric ion (CO-SCFe) and chemical oxidation
      surface grafting with gelatin (CO-SGG), were studied for improving the efficiency
      of wastewater treatment by moving-bed biofilm reactors. The results showed that
      two surface modifications caused corrosion pits to increase surface roughness,
      and brought -(C=O)-/-O-C-O- groups and ferric ions to the biocarrier surface,
      respectively. The positively charged surface increased the hydrophilicity and
      biological affinity of the biocarrier. The biofilm formation rate was improved by
      37.5 and 60% after surface modifications of CO-SCFe and CO-SGG; the concentration
      of biomass on the biocarriers was improved by 54.8 and 76.1% and the COD removal
      efficiencies were increased by 10.63 and 8.64%, respectively. Polymerase chain
      reaction-denaturing gradient gel electrophoresis analysis showed that the
      microbial populations in the biofilm were almost the same after surface
      modifications, but the biomass concentration was greatly increased.

PMID- 22377998
TI  - Visible light assisted photocatalytic degradation of methyl orange using Ag/N
      TiO2 photocatalysts.
AB  - For the sake of efficient utilization of sunlight, Ag nanoparticles loaded N
      doped TiO2 photocatalysts (Ag/N-TiO2) were successfully fabricated via a two-step
      method to make the best use of the respective advantages of noble metal loading
      and nonmetal doping. Ag/N-TiO2 was characterized using XRD, XPS and UV-Vis DRS.
      Compared to TiO2, the dramatic enhancement of the visible-light-induced
      photocatalytic degradation efficiency of Ag/N-TiO2 obtained for the degradation
      of methyl orange should be attributed to the synergistic effect of N-doping and
      Ag-loading, including the good visible light absorption and the effective
      electron-hole separations. This demonstrates Ag/N-TiO2 is a promising
      photocatalytic material for organic pollutant degradation under visible light
      irradiation.

PMID- 22377999
TI  - A novel up-flow inner-cycle anoxic bioreactor (UIAB) system for the treatment of
      sulfide wastewater from purification of biogas.
AB  - An up-flow inner-cycle anoxic bioreactor with a novel three phase separator was
      designed and implemented for the treatment of sulfide wastewater. The sulfide in
      wastewater could be converted to elemental sulfur by sulfide oxidizing bacteria,
      and recovered by simple precipitation. When the oxidation-reduction potential
      (ORP) was controlled at -100 mV, 91.3% of sulfide could be oxidized to elemental
      sulfur. To achieve high removal percentage of sulfide and conversion percentage
      of sulfur, the pH of influent should be controlled in the range from 7.0 to 8.0.
      The optimal desulfurization process was carried out at 400 mmol L(-1)d(-1)
      sulfide loading rate and 120 min hydraulic retention time (HRT). The removal
      percentage of sulfide was approximately 95.2% and elemental sulfur conversion
      percentage was above 90.3%. These results demonstrated that the novel up-flow in
      cycle bioreactor had a potential value for the enhanced treatment of sulfide
      wastewater from biogas purification.

PMID- 22378000
TI  - Preparation, characterization and performance of a novel PVDF/PMMA/TPU blend
      hollow fiber membrane for wastewater treatment.
AB  - Polyvinylidene fluoride (PVDF)/polymethylmethacrylate (PMMA)/thermoplastic
      polyurethane (TPU) blend hollow fiber membranes were successfully prepared by the
      wet-spinning method with the loading of PMMA and TPU in a range of polymer
      concentrations varying from 0 to 20 wt% and at a total polymer concentration of
      16 wt%. The influence of the addition of PMMA and TPU on the morphologies and the
      properties of such prepared membranes was investigated through FTIR-ATR, SEM,
      viscosity measurements, UF experiments and mechanical strength tests. Based on
      the experimental results, the compatibility of the PVDF, PMMA and TPU blend was
      best under the conditions of the PVDF-rich phase. The elongation at break of the
      membrane increased to a maximum of 146% with increase in the TPU concentration to
      20 wt% in dope solution. The addition of PMMA increased the water permeation flux
      from 120 to 195 L/(m(2) h) initially. The flux then decreased when PMMA
      concentration was increased to over 10 wt%. The membranes obtained at optimized
      blending ratio were applied to the dyeing process wastewater filtration. During
      continuous filtration for 8 h, the flux was stabilized at about 20 L/(m(2) h) at
      0.1 MPa. The reduction in COD(Cr), turbidity and color were about 63, 84 and 63%
      respectively.

PMID- 22378001
TI  - An approach for phosphate removal with quartz sand, ceramsite, blast furnace slag
      and steel slag as seed crystal.
AB  - The phosphate removal abilities and crystallization performance of quartz sand,
      ceramsite, blast furnace slag and steel slag were investigated. The residual
      phosphate concentrations in the reaction solutions were not changed by addition
      of the ceramsite, quartz sand and blast furnace slag. The steel slag could
      provide alkalinity and Ca(2+) to the reaction solution due to its hydration
      activity, and performed a better phosphate removal performance than the other
      three. Under the conditions of Ca/P 2.0, pH 8.5 and 10 mg P/L, the phosphate
      crystallization occurred during 12 h. The quartz sand and ceramsite did not
      improve the phosphate crystallization, but steel slag was an effective seed
      crystal. The phosphate concentration decreased drastically after 12 h after
      addition of steel slag, and near complete removal was achieved after 48 h. The
      XRD analysis showed that the main crystallization products were hydroxyapatite
      (HAP) and the crystallinity increased with the reaction time. Phosphate was
      successfully recovered from low phosphate concentration wastewater using steel
      slag as seed material.

PMID- 22378002
TI  - Hierarchical MnO2 nanostructures: synthesis and their application in water
      treatment.
AB  - Hierarchical MnO2 nanostructures were prepared through the reaction between KMnO4
      and oleic acid at room temperature in the surfactant-free microemulsion system.
      The obtained samples were characterized by powder X-ray diffraction, N2
      adsorption, scanning electron microscopy, and transmission electron microscopy.
      The results indicated that the flowerlike nanospheres were three-dimensional (3D)
      porous microstructures consisting of nanoplates. The surface area of the sample
      was 171.5 m(2)/g and the distribution of pore diameter lay within the range of 5
      15 nm. The prepared hierarchically structured MnO2 showed excellent adsorption
      capacity and rapid adsorption rate for methylene blue ions in water. The maximum
      adsorption capacity of methylene blue was as high as 273.9 mg/g and 97.5% of the
      dye was removed within initial 5 min of contact time. Compared with other
      adsorbents, the synthesized hierarchical MnO2 nanostructures displayed a faster
      adsorption rate and higher adsorption capacity, which implied potential
      application for removing dye pollutants from waste water.

PMID- 22378003
TI  - Effects of surfactant on bubble hydrodynamic behavior under flotation-related
      conditions in wastewater.
AB  - Bubble behavior is fundamental to the performance of froth flotation operations
      used in wastewater treatment processes. To fully understand and characterize
      bubble behavior under flotation-related conditions in wastewater, the high-speed
      photographic method has been employed to examine the motion of single bubbles and
      size distribution of bubble swarms with intermediate sizes ranging from 1 to 4 mm
      in the presence of surfactants in a laboratory scale flotation column. Both
      distilled water and synthetic municipal wastewater have been used to make
      solutions as well as two types of common surfactants. The instantaneous bubble
      motion has been recorded by a high speed camera. Subsequently, bubble trajectory,
      dimensions, velocity and distribution have been determined from the recorded
      frames using the image analysis software. The experimental results show that the
      addition of surfactant into wastewater has similar effects on bubble hydrodynamic
      behavior as in pure water (e.g., improving trajectory stabilization, dampening
      bubble deformation, slowing down terminal velocity, reducing bubble size and
      increasing the specific surface area of bubble swarm) due to the Marangoni
      effect. However, it is interesting to note that surfactant effects on single
      bubble hydrodynamics in wastewater are slightly stronger than those in pure water
      while surfactant effects on size parameters of bubble swarms in wastewater are
      significantly stronger than those in pure water. This finding suggests that
      besides surfactant, inorganic salts present in synthetic wastewater have an
      important influence on bubble dispersion.

PMID- 22378004
TI  - Stochastic modeling to identify requirements for centralized monitoring of
      distributed wastewater treatment.
AB  - Distributed (decentralized) wastewater treatment can, in many situations, be a
      valuable alternative to a centralized sewer network and wastewater treatment
      plant. However, it is critical for its acceptance whether the same overall
      treatment performance can be achieved without on-site staff, and whether its
      performance can be measured. In this paper we argue and illustrate that the
      system performance depends not only on the design performance and reliability of
      the individual treatment units, but also significantly on the monitoring scheme,
      i.e. on the reliability of the process information. For this purpose, we present
      a simple model of a fleet of identical treatment units. Thereby, their
      performance depends on four stochastic variables: the reliability of the
      treatment unit, the respond time for the repair of failed units, the reliability
      of on-line sensors, and the frequency of routine inspections. The simulated
      scenarios show a significant difference between the true performance and the
      observations by the sensors and inspections. The results also illustrate the
      trade-off between investing in reactor and sensor technology and in human
      interventions in order to achieve a certain target performance. Modeling can
      quantify such effects and thereby support the identification of requirements for
      the centralized monitoring of distributed treatment units. The model approach is
      generic and can be extended and applied to various distributed wastewater
      treatment technologies and contexts.

PMID- 22378005
TI  - Seasonal variation of fecal indicator bacteria in storm events within the US
      stormwater database.
AB  - Bacteria are one of the major causes of surface water impairments in the USA.
      Over the past several years, best management practices, including detention
      basins, manufactured devices, grass swales, filters and bioretention cells have
      been used to remove bacteria and other pollutants from stormwater runoff.
      However, there are data gaps in the comprehensive studies of bacteria
      concentrations in stormwater runoff. In this paper, the event mean concentration
      (EMC) of fecal indicator bacteria (Enterococcus, Escherichia coli, fecal
      Streptococcus group bacteria, and fecal coliform) across the USA was retrieved
      from the international stormwater best management practices database to analyze
      the seasonal variations of inflow and outflow event mean concentrations and
      removal efficiencies. The Kruskal-Wallis test was employed to determine the
      seasonal variations of bacteria indicator concentrations and removals, and the
      two-sample Kolmogorov-Smirnov test was used for comparing different seasonal
      outcomes. The results indicate that all the inflow EMC of FIB in stormwater
      runoff is above the water quality criteria. The seasonal differences of fecal
      Streptococcus group bacteria and fecal coliform are significant. Summer has the
      potential to increase the bacteria EMC and illustrate the seasonal differences.

PMID- 22378006
TI  - Biodegradation of 4-methylaniline in a sequencing batch reactor.
AB  - The biodegradation of the aromatic amine 4-methylaniline (4MA) using an aerobic
      sequencing batch reactor was evaluated. The specific degradation rate showed an
      exponential increase during the acclimation of the microorganisms reaching a
      maximal value of 34 mg 4MA/VSS/h. After the acclimation, the process showed a
      stable operation. A high similarity index was observed, indicating a low
      variation in the population diversity. During this period, the physicochemical
      parameters demonstrated a stable operation of the reactor.

PMID- 22378007
TI  - Critical modeling parameters identified for 3D CFD modeling of rectangular final
      settling tanks for New York City wastewater treatment plants.
AB  - New York City Environmental Protection is in the process of incorporating
      biological nitrogen removal (BNR) in its wastewater treatment plants (WWTPs)
      which entails operating the aeration tanks with higher levels of mixed liquor
      suspended solids (MLSS) than a conventional activated sludge process. The
      objective of this paper is to discuss two of the important parameters introduced
      in the 3D CFD model that has been developed by the City College of New York
      (CCNY) group: (a) the development of the 'discrete particle' measurement
      technique to carry out the fractionation of the solids in the final settling tank
      (FST) which has critical implications in the prediction of the effluent quality;
      and (b) the modification of the floc aggregation (K(A)) and floc break-up (K(B))
      coefficients that are found in Parker's flocculation equation (Parker et al.
      1970, 1971) used in the CFD model. The dependence of these parameters on the
      predictions of the CFD model will be illustrated with simulation results on one
      of the FSTs at the 26th Ward WWTP in Brooklyn, NY.

PMID- 22378008
TI  - Water quality trends in the last decade for ten watersheds dominated by diffuse
      pollution in Quebec (Canada).
AB  - The aim of this work is to evaluate and discuss river water quality trends over
      the last decade in ten watersheds where diffuse pollution represents more than
      half of the annual load of phosphorus (P) and nitrogen (N). Trend analyses taking
      into account flow data indicate a significant reduction of total P in eight
      rivers, of ammonia N in five rivers, of nitrate + nitrite in four rivers, of
      total filtered N in three rivers and of suspended solids in two rivers. An
      increase of turbidity was observed in four rivers and, for fecal coliforms, no
      trends. P decrease can be explained by reduced mineral P inputs on cropped lands
      related to means such as agro-environmental fertilization plans and addition of
      phytase in pig and poultry feed. However, for seven of them, median P
      concentrations remain at least two times greater than the Quebec water quality
      guideline for protection of rivers against eutrophication. Concentrations of
      other parameters remain problematic in some rivers too. These results indicate
      the need to continue the efforts for further diffuse pollution reduction. Future
      work should better quantify actions taken at the watershed scale to reduce
      diffuse pollution.

PMID- 22378009
TI  - Treatment of domestic sewage by a metal membrane bioreactor.
AB  - A submerged flat metal MBR (membrane bioreactor) was used to treat synthetic
      domestic sewage in this study. The experiment was continued for 270 days and ran
      under two modes as AMBR (aerobic membrane bioreactor) and A/O-MBR (anoxic/aerobic
      membrane bioreactor) at a permeate flux of 0.4-1 m3/(m2 d). PVA (polyvinyl
      alcohol) gel beads were added to the aeration tank with a volume ratio of 10% at
      the end of the A/O-MBR mode. The mean COD and TN removal efficiencies achieved
      96.69 and 32.12% under the AMBR mode, and those were 92.17 and 72.44% under the
      A/O-MBR mode, respectively. SND (simultaneous nitrification and denitrification)
      occurred at high MLSS (mixed liquor suspended solids) concentration. The metal
      membranes reduced effluent COD during filtration. The system ran stably for 115
      days at a permeate flux of 0.8-1 m3/(m2 d) without changing membranes under the
      AMBR mode, but the membrane filterability decreased gradually under high MLSS or
      A/O-MBR mode, and the addition of PVA worsened the membrane filterability on the
      contrary. PSD (particle size distribution) and sludge fractions had evident
      influence on membrane fouling. The main fouling mechanism was cake formation
      under the AMBR mode, and that was pore blocking under the A/O-MBR mode.

PMID- 22378010
TI  - Evaluation of a hybrid vertical membrane bioreactor (HVMBR) for wastewater
      treatment.
AB  - A new hybrid membrane bioreactor (HMBR) has been developed to obtain a compact
      module, with a small footprint and low requirement for aeration. The aim of this
      research was to assess its performance. The system consists of a single vertical
      reactor with a filtration membrane unit and, above this, a sponge fixed bed as
      support medium. The aeration system is located under the membrane unit, allowing
      for membrane cleaning, oxygenation, biofilm thickness control and bulk liquid
      mixing. Operated under continuous aeration, a bench-scale reactor (70 L) was fed
      with pre-treated, raw (unsettled) municipal wastewater. BOD(5) and suspended
      solids removal efficiencies (96 and 99% respectively) were comparable to those
      obtained with other membrane bioreactors (MBRs). Total nitrogen removal
      efficiencies of 80% were achieved, which is better than those obtained in other
      HMBRs and similar to the values reached using more complex MBRs with extra anoxic
      tanks, intermittent aeration or internal deflectors.

PMID- 22378011
TI  - A data-driven model for maximization of methane production in a wastewater
      treatment plant.
AB  - A data-driven approach for maximization of methane production in a wastewater
      treatment plant is presented. Industrial data collected on a daily basis was used
      to build the model. Temperature, total solids, volatile solids, detention time
      and pH value were selected as parameters for the model construction. First, a
      prediction model of methane production was built by a multi-layer perceptron
      neural network. Then a particle swarm optimization algorithm was used to maximize
      methane production based on the model developed in this research. The model
      resulted in a 5.5% increase in methane production.

PMID- 22378012
TI  - Model-based knowledge acquisition in environmental decision support system for
      wastewater integrated management.
AB  - The main goal of the Water Framework Directive is to achieve good chemical and
      ecological status of water bodies by 2015. The implementation of integrated river
      basin management, including sewer systems, wastewater treatment plants and
      receiving water bodies, is essential to accomplishing this objective. Integrated
      management is complex and therefore the implementation of control systems and the
      development of decision support systems are needed to facilitate the work of
      urban wastewater system (UWS) managers. Within this context, the objective of
      this paper is to apply integrated modelling of an UWS to simulate and analyse the
      behaviour of the 'Congost' UWS in Spain, and to optimize its performance against
      different types of perturbations. This analysis results in optimal operating set
      points for each perturbation, improves river water quality, minimizes combined
      sewer overflows and optimizes flow lamination from storm water tanks. This is
      achieved by running Monte Carlo simulations and applying global sensitivity
      analysis. The set-points will become part of the knowledge base composed of a set
      of IF-THEN rules of the environmental decision support system being developed for
      this case study.

PMID- 22378013
TI  - A mechanistic model for fate and removal of estrogens in biological nutrient
      removal activated sludge systems.
AB  - Two estrogen fate and transformation models were integrated with a comprehensive
      activated sludge model (ASM) to predict estrogen removal based on biomass and
      solids production. Model predictions were evaluated against published full-scale
      plant data as well as results from a laboratory-scale sequencing batch reactor
      (SBR) fed synthetic wastewater. The estrogen fate model relating the rate of
      total estrogen degradation to soluble estrogen concentrations successfully
      predicted estrogen removals when compared with measured concentrations. Model fit
      17alpha-ethinylestradiol (EE2) biodegradation rate constant was 19 to 43% of the
      estrone (E1) value and 31 to 72% of the 17beta-estradiol (E2) value.

PMID- 22378014
TI  - Testing the effectiveness of monolayers under wind and wave conditions.
AB  - Monolayers are highly desirable for their evaporation reducing capabilities due
      to their relatively minimal cost and ease of application. Despite these positive
      attributes, monolayers have consistently failed to perform effectively due to the
      harsh wind and wave conditions prevalent across real-world water reserves. An
      exhaustive and consistent study testing the influence of wind and wave
      combinations on monolayer performance has yet to be presented in the literature.
      To remedy this, the effect of simultaneous wind and wave conditions on a
      benchmark high-performance monolayer (octadecanol suspension,
      CH(3)(CH(2))(16)CH(2)OH) has been analysed. Subjected only to waves, the
      monolayer remained intact due to its innate ability to compress and expand.
      However, the constant simultaneous application of wind and waves caused the
      monolayer to break up and gather down-wind where it volatilised over time. At
      wind speeds above 1.3 m s(-1) the monolayer was completely ineffective. For wind
      speeds below this threshold, the monolayer had an influence on the evaporation
      rate dependent on wind speed. From these results a series of application
      protocols can now be developed for the optimised deployment of monolayers in real
      world water reserves. This will be of interest to private, commercial and
      government organisations involved in the storage and management of water
      resources.

PMID- 22378015
TI  - Methane potential and biodegradability of rice straw, rice husk and rice residues
      from the drying process.
AB  - Agricultural solid residues are a potential renewable energy source. Rice
      harvesting and production in Sancti Spiritus province, Cuba, currently generates
      residues without an environmentally sustainable disposal route. Rice residues
      (rice straw, rice husk and rice residues from the drying process) are potentially
      an important carbon source for anaerobic digestion. For this paper, rice residues
      were placed for 36 days retention time in anaerobic batch reactor environments at
      both mesophilic (37  degrees C) and thermophilic (55  degrees C) conditions.
      Biogas and methane yield were determined as well as biogas composition. The
      results showed that rice straw as well as rice residues from the drying process
      had the highest biogas and methane yield. Temperature played an important role in
      determining both biogas yield and kinetics. In all cases, rice straw produced the
      highest yields; under mesophilic conditions the biogas yield was 0.43 m(3)
      kg(VS)(-1), under thermophilic conditions biogas yield reached 0.52 m(3) kg(VS)(
      1). In the case of the rice husk, the biodegradability was very low. Methane
      content in all batches was kept above 55% vol. All digested material had a high
      carbon:nitrogen (C:N) ratio, even though significant biodegradation was recorded
      with the exception of rice husk. A first-order model can be used to describe the
      rice crop residues fermentation effectively.

PMID- 22378016
TI  - In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted
      LipoCEST contrast agent at 7 T.
AB  - LipoCEST are liposome-encapsulating paramagnetic contrast agents (CA) based on
      chemical exchange saturation transfer with applications in biomolecular MRI.
      Their attractive features include biocompatibility, subnanomolar sensitivity, and
      amenability to functionalization for targeting biomarkers. We demonstrate MR
      imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying
      Tm(III)-complexes was conjugated to RGD tripeptide (RGD-lipoCEST), to target
      integrin alpha(nu)beta(3) receptors involved in tumor angiogenesis and was
      compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude
      mice by intracerebral injection of U87MG cells and were imaged at 7 T after
      intravenous injection of either of the two contrast agents (n = 12 for each
      group). Chemical exchange saturation transfer-MSME sequence was applied over 2 h
      with an average acquisition time interval of 13.5 min. The chemical exchange
      saturation transfer signal was ~1% in the tumor and controlateral regions, and
      decreased to ~0.3% after 2 h; while RGD-lipoCEST signal was ~1.4% in the tumor
      region and persisted for up to 2 h. Immunohistochemical staining revealed a
      persistent colocalization of RGD-lipoCEST with alpha(nu)beta(3) receptors in the
      tumor region. These results constitute an encouraging step toward in vivo MRI
      imaging of tumor angiogenesis using intravenously injected lipoCEST.

PMID- 22378018
TI  - Annexin A1 mediates the anti-inflammatory effects during the granulocytic
      differentiation process in all-trans retinoic acid-treated acute promyelocytic
      leukemic cells.
AB  - Annexin A1 (AnxA1) originating from mature neutrophils and their microparticles
      (MPs) plays an important anti-inflammatory role during the resolution phase of
      inflammation. However, the role of AnxA1 during the process of granulocytic
      differentiation is still unknown. All-trans retinoic acid (ATRA) can induce acute
      promyelocytic leukemic (APL) cells to differentiate along the granulocytic
      lineage and has been used successfully in treating APL patients. In this study,
      we investigated whether or not AnxA1 contributed to the anti-inflammatory
      properties of ATRA-treated APL (NB4; ATRA-NB) cells using the transmigratory and
      adhesive assays. We found that ATRA was able to enhance the surface expression of
      AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1-containing MPs from
      ATRA-NB4 cells, while the expression of annexin V was not elevated on the latter
      cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA-NB4
      cells in their transmigratory activity and adhesion to endothelial cells. In
      addition, the transmigratory activity of ATRA-NB4 cells can be significantly
      enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that
      endogenous AnxA1 may contribute to the anti-migratory effects. Finally, ATRA-NB4
      derived MPs could also inhibit recipient cells in their transmigratory and
      adhesive activities and these anti-inflammatory effects could be inhibited by
      pretreatment of MPs with a specific anti-AnxA1 antibody. Flowcytometry studies
      further demonstrated that FITC-labeled AnxA1 could be transported from MPs to the
      membrane of recipient ATRA-NB4 cells. We conclude that biologically active AnxA1
      may play a role in the anti-inflammatory properties of ATRA-treated APL cells
      during the process of granulocytic differentiation.

PMID- 22378019
TI  - Size-dependent surface activity of rutile and anatase TiO2 nanocrystals: facile
      surface modification and enhanced photocatalytic performance.
AB  - The size-dependent surface activity of titania was illustrated through the
      formation of ultrafine nanocrystals with clean surfaces. It was demonstrated
      that, when the size of the nanocrystals was small enough, their surface activity
      could be significantly enhanced, as evidenced by the formation of transparent
      macroassemblies, their increased dispersity in various solvents, the facile
      modification of their surface by organic molecules at room temperature, their
      strong visible-light absorption through coordination with peroxide, and highly
      enhanced photocatalytic performance.

PMID- 22378017
TI  - Fibrosis-dependent mechanisms of hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is a rising worldwide cause of cancer mortality,
      making the elucidation of its underlying mechanisms an urgent priority. The liver
      is unique in its response to injury, simultaneously undergoing regeneration and
      fibrosis. HCC occurs in the context of these two divergent responses, leading to
      distinctive pathways of carcinogenesis. In this review we highlight pathways of
      liver tumorigenesis that depend on, or are enhanced by, fibrosis. Activated
      hepatic stellate cells drive fibrogenesis, changing the composition of the
      extracellular matrix. Matrix quantity and stiffness also increase, providing a
      reservoir for bound growth factors. In addition to promoting angiogenesis, these
      factors may enhance the survival of both preneoplastic hepatocytes and activated
      hepatic stellate cells. Fibrotic changes also modulate the activity of
      inflammatory cells in the liver, reducing the activity of natural killer and
      natural killer T cells that normally contribute to tumor surveillance. These
      pathways synergize with inflammatory signals, including telomerase reactivation
      and reactive oxygen species release, ultimately resulting in cancer. Clarifying
      fibrosis-dependent tumorigenic mechanisms will help rationalize antifibrotic
      therapies as a strategy to prevent and treat HCC.

PMID- 22378020
TI  - The effect of NET-1 on the proliferation, migration and endocytosis of the SMMC
      7721 HCC cell line.
AB  - To explore the effect of NET-1 on the proliferation, migration and endocytosis in
      the hepatocellular carcinoma (HCC) cell line SMMC-7721, we constructed the pU6H1
      NET-1-siRNA (NET-1siRNA) and pcDNA3.1/myc-NET-1 (myc-NET-1) vectors and
      transfected them into SMMC-7721 cells. The expression levels of NET-1 mRNA and
      protein were detected using real-time quantitative RT-QPCR and western blotting.
      The proliferation rates of SMMC-7721 cells were determined by CCK-8 assays, flow
      cytometry (FCM) and immunohistochemistry staining. The migration in two or three
      dimensional space of SMMC-7721 cells were determined by wound-healing assay and
      in vitro invasion assay. The extent of endocytosis in SMMC-7721 cells was
      estimated by observing the amount of transferrin (Tfn) absorbed with capture
      ELISA assays, and Tfn endocytosis was observed under confocal immunofluorescence
      microscopy. The results show that: i) after transfecting NET-1 siRNA, the
      expression of NET-1 mRNA and protein in SMMC-7721 cells decreased significantly,
      the growth of cells was suppressed, which induced cell cycle arrest, the
      proliferation rates were dramatically reduced and the expression of Ki67
      declined, and migration and endocytosis in cells were inhibited, compared with
      untreated cells (every P<0.01); ii) Following transfection with myc-NET-1, the
      expression of NET-1 mRNA and protein in SMMC-7721 cells increased, and both the
      proliferation of cells and the cell cycle were promoted (P<0.01, respectively).
      However, the abilities of cell migration and endocytosis were not affected
      compared with untreated cells. These data suggest that: i) the NET-1 gene may
      play an important role in proliferation, migration and endocytosis of cells; ii)
      siRNA technology may efficiently suppress the expression and function of NET-1 in
      HCC, suggesting that NET-1 may be a therapeutic target for HCC.

PMID- 22378021
TI  - Abnormal mitochondria organization and oxidative activity in the palate muscles
      of long-term snorers with obstructive sleep apnea.
AB  - BACKGROUND: Histopathological alterations and a reduced number of capillaries
      have been observed in the palate muscles of snorers with obstructive sleep apnea
      syndrome (OSAS). These changes may create a substrate for decreased
      microcirculation, impaired aerobic metabolism and muscle dysfunction and
      contribute to upper airway obstruction during sleep. OBJECTIVES: The aim was to
      analyze mitochondria distribution and oxidative enzyme activity in relation to
      capillary supply in the palate muscles of patients with a history of long-term
      snoring and OSAS. METHODS: Palatopharyngeus (PP) and uvula (UV) muscle samples
      were obtained from 8 patients undergoing uvulopalatopharyngoplasty due to
      habitual snoring and OSAS. The muscles were analyzed with enzyme- and
      immunohistochemistry and morphometry. RESULTS: Abnormalities in the internal
      organization of mitochondria and oxidative activity were observed in 39 +/- 15%
      of the fibers in the PP and 4 +/- 3% in the UV, but not in control samples. The
      majority of these fibers had a lobulated contour and trabecular internal
      organization of mitochondria. The number of capillaries around abnormal fibers
      (PP 0.9 +/- 0.3, UV 0.4 +/- 0.1) was lower than in fibers of a normal appearance
      in both patients (PP 1.4 +/- 0.6, UV 1.2 +/- 0.3) and references (PP 2.7 +/- 0.7,
      UV 1.9 +/- 0.9) (p < 0.05). CONCLUSIONS: Abnormal mitochondrial distribution, a
      low capillary supply and signs of impaired oxidative activity suggest that muscle
      dysfunction of the palate muscles in long-term snorers may contribute to the
      upper airway obstruction during sleep. The cause of these abnormalities remains
      unclear, but local muscle and nerve trauma due to vibration and stretch is a
      possible etiology.

PMID- 22378022
TI  - Is neuregulin 1 involved in determining cerebral volumes in schizophrenia?
      Preliminary results showing a decrease in superior temporal gyrus volume.
AB  - BACKGROUND/AIMS: Reduced left superior temporal gyrus (STG) volume is one of the
      most replicated imaging findings in schizophrenia. However, it remains unclear
      whether genes play any role in our understanding of such structural alteration.
      It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved
      in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In
      this study, the association between NRG1 and STG anatomy in patients with
      schizophrenia was explored for the first time. METHODS: We investigated a 1-year
      treated prevalence cohort of patients with schizophrenia in contact with the
      South Verona Community-Based Mental Health Service. A blood sample was collected
      for DNA extraction and brain structure was assessed with an MRI scan. A total of
      27 subjects with schizophrenia underwent both assessments and were included in
      the study. RESULTS: We investigated the association between the polymorphism
      SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients
      homozygous for the C allele had reduced left STG gray and white matter volumes in
      comparison to those homozygous for the G allele (p < 0.01 and p < 0.001,
      respectively). CONCLUSIONS: This exploratory study suggests that NRG1 may be
      involved in determining STG size in schizophrenia, and may play a role in the
      neurogenetic basis of the language disturbances seen in this disorder. However,
      due to our small sample size, the results should be regarded as preliminary and
      replicated in a larger sample.

PMID- 22378023
TI  - Quasi-dynamic mode of nanomembranes for time-of-flight mass spectrometry of
      proteins.
AB  - Mechanical resonators realized on the nano-scale by now offer applications in
      mass-sensing of biomolecules with extraordinary sensitivity. The general idea is
      that perfect mechanical biosensors should be of extremely small size to achieve
      zeptogram sensitivity in weighing single molecules similar to a balance. However,
      the small scale and long response time of weighing biomolecules with a cantilever
      restrict their usefulness as a high-throughput method. Commercial mass
      spectrometry (MS) such as electro-spray ionization (ESI)-MS and matrix-assisted
      laser desorption/ionization (MALDI)-time of flight (TOF)-MS are the gold
      standards to which nanomechanical resonators have to live up to. These two
      methods rely on the ionization and acceleration of biomolecules and the following
      ion detection after a mass selection step, such as time-of-flight (TOF). Hence,
      the spectrum is typically represented in m/z, i.e. the mass to ionization charge
      ratio. Here, we describe the feasibility and mass range of detection of a new
      mechanical approach for ion detection in time-of-flight mass spectrometry, the
      principle of which is that the impinging ion packets excite mechanical
      oscillations in a silicon nitride nanomembrane. These mechanical oscillations are
      henceforth detected via field emission of electrons from the nanomembrane. Ion
      detection is demonstrated in MALDI-TOF analysis over a broad range with
      angiotensin, bovine serum albumin (BSA), and an equimolar protein mixture of
      insulin, BSA, and immunoglobulin G (IgG). We find an unprecedented mass range of
      operation of the nanomembrane detector.

PMID- 22378024
TI  - Visual detection of copper(II) ions in blood samples by controlling the leaching
      of protein-capped gold nanoparticles.
AB  - We have developed a simple, low-cost, paper-based probe for the selective
      colorimetric detection of copper ions (Cu(2+)) in aqueous solutions. The bovine
      serum albumin (BSA)-modified 13.3-nm Au nanoparticle (BSA-Au NP) probe was
      designed to detect Cu(2+) ions using lead ions (Pb(2+)) and 2-mercaptoethanol (2
      ME) as leaching agents in a glycine-NaOH (pH 12.0) solution. In addition, a
      nitrocellulose membrane (NCM) was used to trap the BSA-Au NPs, leading to the
      preparation of a nanocomposite film consisting of a BSA-Au NP-decorated membrane
      (BSA-Au NPs/NCM). The BSA-Au NPs probe operates on the principle that Cu
      deposition on the surface of the BSA-Au NPs inhibits their leaching ability,
      which is accelerated by Pb(2+) ions in the presence of 2-ME. Under optimal
      solution conditions (5 mM glycine-NaOH (pH 12.0), Pb(2+) (50 MUM), and 2-ME (1.0
      M)), the Pb(2+)/2-ME-BSA-Au NPs/NCM enabled the detection of Cu(2+) at nanomolar
      concentrations in aqueous solutions by the naked eye with high selectivity (at
      least 100-fold over other metal ions). In addition, this cost-effective probe
      allowed for the rapid and simple determination of Cu(2+) ions in not only natural
      water samples but also in a complex biological sample (in this case, blood
      sample).

PMID- 22378025
TI  - A silica-induced pulmonary fibrosis model: are we closer to 'real life'?

PMID- 22378026
TI  - The need for increased clarity and transparency in the regulatory pathway for
      gene medicines in the European Union.

PMID- 22378029
TI  - Escaping the valley of death.

PMID- 22378030
TI  - Clinical development of advanced therapy medicinal products in Europe: evidence
      that regulators must be proactive.

PMID- 22378031
TI  - 1,2-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential
      antimalarial agents.
AB  - This work presents a new family of organometallic antimalarial compounds
      consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5
      diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2
      substitution pattern. The synthetic route proceeds via a stereoselective
      functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted
      conjugates. After complete characterization of these new, trifunctional
      conjugates, they were examined for their cytotoxicity in two cancerous cell lines
      (MDA-MB-435S and Caco2) and one non-cancerous cell line (MCF-10A), showing that
      increased cytotoxicity can be observed for the chloroquine ferrocenyl conjugates
      compared to their carbohydrate-substituted precursors. The antiplasmodial
      activity of the conjugates in a chloroquine-sensitive strain of Plasmodium
      falciparum (D10) and a chloroquine-resistant strain (Dd2) was determined.
      Monosubstituted conjugates 13, 14 and 15 exhibit decreasing activity with
      increasing alkyl chain length between the ferrocene and quinoline moiety,
      bifunctional conjugates 16, 17, 18 show constant activity, performing better than
      chloroquine in the Dd2 strain.

PMID- 22378032
TI  - Quantification of plasmacytoid dendritic cells and type 1 myeloid dendritic cells
      in peripheral blood of renal transplant recipients with and without squamous cell
      carcinoma.

PMID- 22378033
TI  - Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats
      with chronic renal failure.
AB  - BACKGROUND: Cardiotonic steroids (CTS) are implicated in pathophysiology of
      uremic cardiomyopathy. In the present study, we tested whether a monoclonal
      antibody (mAb) against the bufadienolide CTS, marinobufagenin (MBG), alleviates
      cardiac hypertrophy and fibrosis in partially nephrectomized (PNx) rats. METHODS:
      In PNx rats, we compared the effects of 3E9 anti-MBG mAb and of Digibind, an
      affinity-purified digoxin antibody, on blood pressure and cardiac hypertrophy and
      fibrosis following 4 weeks after the surgery. RESULTS: In PNx rats, a fourfold
      elevation in plasma MBG levels was associated with hypertension, increased
      cardiac levels of carbonylated protein, cardiac hypertrophy, a reduction in
      cardiac expression of a nuclear transcription factor which is a negative
      regulator of collagen synthesis, Friend leukemia integration-1 (Fli-1), and an
      increase in the levels of collagen-1. A single intraperitoneal administration of
      3E9 mAb to PNx rats reduced blood pressure by 59 mm Hg for 7 days and produced a
      significant reduction in cardiac weight and cardiac levels of oxidative stress,
      an increase in the expression of Fli-1, and a reduction in cardiac fibrosis. The
      effects of Digibind were similar to those of 3E9 mAb, but were less pronounced.
      CONCLUSIONS: In experimental chronic renal failure, elevated levels of MBG
      contribute to hypertension and induce cardiac fibrosis via suppression of Fli-1,
      representing a potential target for therapy.

PMID- 22378034
TI  - Association of uric acid with progression to preeclampsia and development of
      adverse conditions in gestational hypertensive pregnancies.
AB  - BACKGROUND: Preeclampsia is a serious pregnancy complication. Gestational
      hypertension is a common first clinical presentation of preeclampsia. Little is
      known about which clinical risk factors are associated with the progression from
      gestational hypertension to preeclampsia. METHODS: In a retrospective cohort
      study of 249 singleton pregnant women with an initial presentation of gestational
      hypertension in an obstetric hospital, we assessed which routinely available
      clinical risk factors are associated with the progression to preeclampsia and the
      development of adverse maternal or infant conditions. RESULTS: The mean serum
      uric acid level at the initial presentation of gestational hypertension was
      significantly higher comparing patients who later progressed to preeclampsia to
      those who did not (5.06 vs. 4.59 mg/dl, P < 0.01). Lower gestational age and
      higher serum uric acid level at the initial presentation of gestational
      hypertension and subsequent need for antihypertensive drug treatment for blood
      pressure (BP) control were associated with significantly increased risks of
      progression to preeclampsia, and development of adverse maternal or infant
      conditions. One standard deviation (s.d.) increase in serum uric acid level was
      associated with 2.3-fold increased odds of progression to preeclampsia (adjusted
      odds ratio (aORs) 2.33 (95% confidence interval (CI) 1.45-3.74)), and 1.5-fold
      increased odds of developing clinically significant adverse maternal or infant
      conditions (aOR 1.49 (1.03-2.17)) irrespective of the progression to
      preeclampsia. CONCLUSIONS: Higher serum uric acid levels at the initial
      presentation of gestational hypertension may indicate heightened risk of
      progression to preeclampsia and development of adverse maternal/infant
      conditions.

PMID- 22378035
TI  - Masked hypertension and prehypertension: diagnostic overlap and
      interrelationships with left ventricular mass: the Masked Hypertension Study.
AB  - BACKGROUND: Masked hypertension (MHT) and prehypertension (PHT) are both
      associated with an increase in cardiovascular disease (CVD) risk, relative to
      sustained normotension. This study examined the diagnostic overlap between MHT
      and PHT, and their interrelationships with left ventricular (LV) mass index
      (LVMI), a marker of cardiovascular end-organ damage. METHODS: A research nurse
      performed three manual clinic blood pressure (CBP) measurements on three
      occasions over a 3-week period (total of nine readings, which were averaged) in
      813 participants without treated hypertension from the Masked Hypertension Study,
      an ongoing worksite-based, population study. Twenty-four-hour ambulatory blood
      pressure (ABP) was assessed by using a SpaceLabs 90207 monitor. LVMI was
      determined by echocardiography in 784 (96.4%) participants. RESULTS: Of the 813
      participants, 769 (94.6%) had normal CBP levels (<140/90 mm Hg). One hundred and
      seventeen (15.2%) participants with normal CBP had MHT (normal CBP and mean awake
      ABP >=135/85 mm Hg) and 287 (37.3%) had PHT (mean CBP 120-139/80-89 mm Hg). 83.8%
      of MHT participants had PHT and 34.1% of PHT participants had MHT. MHT was
      infrequent (3.9%) when CBP was optimal (<120/80 mm Hg). After adjusting for age,
      gender, body mass index (BMI), race/ethnicity, history of high cholesterol,
      history of diabetes, current smoking, family history of hypertension, and
      physical activity, compared with optimal CBP with MHT participants, LVMI was
      significantly greater in PHT without MHT participants and in PHT with MHT
      participants. CONCLUSIONS: In this community sample, there was substantial
      diagnostic overlap between MHT and PHT. The diagnosis of MHT using an ABP monitor
      may not be warranted for individuals with optimal CBP.

PMID- 22378036
TI  - Effect of 1-year anti-TNF-alpha therapy on aortic stiffness, carotid
      atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled
      study.
AB  - BACKGROUND: Premature arterial stiffening and atherosclerosis are increased in
      patients with inflammatory arthropathies such as rheumatoid arthritis (RA),
      ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The proinflammatory
      protein calprotectin is associated with inflammatory arthropathies, vascular
      pathology, and acute coronary events. We examined the long-term effects of
      treatment with tumor necrosis factor (TNF)-alpha antagonists on aortic stiffness
      and carotid intima media thickness (CIMT) in patients with inflammatory
      arthropathies, and the relationships to the levels of calprotectin. METHODS:
      Fifty-five patients with RA, AS, or PsA and a clinical indication for anti-TNF
      alpha therapy were included and followed with regular examinations for 1 year.
      Thirty-six patients starting with anti-TNF-alpha therapy were compared with a
      nontreatment group of 19 patients. Examinations included assessments of aortic
      stiffness (aortic pulse wave velocity, aPWV), CIMT, and plasma calprotectin.
      RESULTS: After 1 year, aPWV (mean (s.d.)) was improved in the treatment group,
      but not in the control group (-0.54 [0.79] m/s vs. 0.06 [0.61] m/s, respectively;
      P = 0.004), and CIMT progression (median (quartile cut-points, 25th and 75th
      percentiles)) was reduced in the treatment group compared to the control group (
      0.002 [-0.038, 0.030] mm vs. 0.030 [0.011, 0.043] mm, respectively; P = 0.01). In
      multivariable analyses, anti-TNF-alpha therapy over time was associated with
      improved aPWV (P = 0.02) and reduced CIMT progression (P = 0.04), and
      calprotectin was longitudinally associated with aPWV (P = 0.02). CONCLUSIONS:
      Long-term anti-TNF-alpha therapy improved aortic stiffness and CIMT progression
      in patients with inflammatory arthropathies. Calprotectin may be a soluble
      biomarker reflecting aortic stiffening in these patients.

PMID- 22378037
TI  - Overexpression of mouse angiotensinogen in renal proximal tubule causes salt
      sensitive hypertension in mice.
AB  - BACKGROUND: The role of proximal tubule (PT) angiotensinogen (AGT) in modulating
      blood pressure has previously been examined using mice expressing PT human AGT
      and human renin, or rat AGT. These animals are hypertensive; however, the
      question remains whether alterations in mouse PT AGT alone affects arterial
      pressure. METHODS: Mouse AGT cDNA was knocked-in to the endogenous kidney
      androgen protein (KAP) gene using an internal ribosomal entry site (IRES)-based
      strategy. RESULTS: The KAP-mAGT animals showed kidney-specific KAP-AGT mRNA
      expression; renal in situ hybridization detected KAP-AGT mRNA only in PT. Urinary
      AGT was markedly increased in KAP-mAGT mice. On a high Na diet, radiotelemetric
      arterial pressure showed a systolic pressure elevation; no significant difference
      in arterial pressure was observed on a normal diet. Plasma renin concentration
      (PRC) was reduced in KAP-mAGT animals given a high Na diet, but was not different
      between mouse lines during normal Na intake. Plasma AGT concentration was not
      altered by overexpression of PT mouse AGT. CONCLUSIONS: In summary, PT
      overexpression of mouse AGT leads to salt-sensitive hypertension without
      recruitment of the systemic renin-angiotensin system.

PMID- 22378039
TI  - Multistep activation of the Helicobacter pylori effector CagA.
AB  - Chronic infection with the Gram-negative bacterium Helicobacter pylori is a major
      risk factor for the development of gastric cancer. Accumulating evidence
      indicates that the H. pylori virulence determinant cytotoxin-associated gene A
      (CagA) has a key oncogenic role in the process. Certain biological activities of
      CagA require its tyrosine phosphorylation by host cell kinases. In this issue of
      the JCI, Mueller and colleagues report their detailed kinetic and functional
      analysis of CagA phosphorylation, which indicates that c-Src and c-Abl kinases
      sequentially phosphorylate CagA. Interestingly, the two phosphorylation events
      need not occur on the same CagA molecule but are both required for the biological
      effects of CagA. The results provide a clinically relevant example of how a
      successful bacterial pathogen has evolved to exploit the tightly coordinated,
      sequential activity of host cell kinases for virulence factor activation and
      induction of pathology.

PMID- 22378040
TI  - ErbB-2 signals through Plexin-B1 to promote breast cancer metastasis.
AB  - Diagnosis of metastatic breast cancer is associated with a very poor prognosis.
      New therapeutic targets are urgently needed, but their development is hampered by
      a lack of understanding of the mechanisms leading to tumor metastasis.
      Exemplifying this is the fact that the approximately 30% of all breast cancers
      overexpressing the receptor tyrosine kinase ErbB-2 are characterized by high
      metastatic potential and poor prognosis, but the signaling events downstream of
      ErbB-2 that drive cancer cell invasion and metastasis remain incompletely
      understood. Here we show that overexpression of ErbB-2 in human breast cancer
      cell lines leads to phosphorylation and activation of the semaphorin receptor
      Plexin-B1. This was required for ErbB-2-dependent activation of the pro
      metastatic small GTPases RhoA and RhoC and promoted invasive behavior of human
      breast cancer cells. In a mouse model of ErbB-2-overexpressing breast cancer,
      ablation of the gene encoding Plexin-B1 strongly reduced the occurrence of
      metastases. Moreover, in human patients with ErbB-2-overexpressing breast cancer,
      low levels of Plexin-B1 expression correlated with good prognosis. Our data
      suggest that Plexin-B1 represents a new candidate therapeutic target for treating
      patients with ErbB-2-positive breast cancer.

PMID- 22378041
TI  - Evidence for a stepwise program of extrathymic T cell development within the
      human tonsil.
AB  - The development of a broad repertoire of T cells, which is essential for
      effective immune function, occurs in the thymus. Although some data suggest that
      T cell development can occur extrathymically, many researchers remain skeptical
      that extrathymic T cell development has an important role in generating the T
      cell repertoire in healthy individuals. However, it may be important in the
      setting of poor thymic function or congenital deficit and in the context of
      autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a
      stepwise program of T cell development occurs within the human tonsil. We
      identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin-
      cells, which resemble multipotent progenitors in the bone marrow and thymus; (b)
      more mature CD34+CD38brightLin- cells; (c) CD34+CD1a+CD11c- cells, which resemble
      committed T cell lineage precursors in the thymus; (d) CD34-CD1a+CD3-CD11c-
      cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e)
      CD34-CD1a+CD3+CD11c- cells. The phenotype of each subset closely resembled that
      of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes
      required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell
      differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed
      CD34 and/or CD1a, indicating that this distinct anatomic region contributes to
      pre-T cell development, as does the subcapsular region of the thymus. Thus, we
      provide evidence of a role for the human tonsil in a comprehensive program of
      extrathymic T cell development.

PMID- 22378042
TI  - c-Src and c-Abl kinases control hierarchic phosphorylation and function of the
      CagA effector protein in Western and East Asian Helicobacter pylori strains.
AB  - Many bacterial pathogens inject into host cells effector proteins that are
      substrates for host tyrosine kinases such as Src and Abl family kinases.
      Phosphorylated effectors eventually subvert host cell signaling, aiding disease
      development. In the case of the gastric pathogen Helicobacter pylori, which is a
      major risk factor for the development of gastric cancer, the only known effector
      protein injected into host cells is the oncoprotein CagA. Here, we followed the
      hierarchic tyrosine phosphorylation of H. pylori CagA as a model system to study
      early effector phosphorylation processes. Translocated CagA is phosphorylated on
      Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs EPIYA-A, EPIYA-B, and EPIYA-C in Western
      strains of H. pylori and EPIYA-A, EPIYA-B, and EPIYA-D in East Asian strains. We
      found that c-Src only phosphorylated EPIYA-C and EPIYA-D, whereas c-Abl
      phosphorylated EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D. Further analysis revealed
      that CagA molecules were phosphorylated on 1 or 2 EPIYA motifs, but never
      simultaneously on 3 motifs. Furthermore, none of the phosphorylated EPIYA motifs
      alone was sufficient for inducing AGS cell scattering and elongation. The
      preferred combination of phosphorylated EPIYA motifs in Western strains was EPIYA
      A and EPIYA-C, either across 2 CagA molecules or simultaneously on 1. Our study
      thus identifies a tightly regulated hierarchic phosphorylation model for CagA
      starting at EPIYA-C/D, followed by phosphorylation of EPIYA-A or EPIYA-B. These
      results provide insight for clinical H. pylori typing and clarify the role of
      phosphorylated bacterial effector proteins in pathogenesis.

PMID- 22378043
TI  - The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice
      involves mitochondrial damage and nuclear DNA fragmentation.
AB  - Acetaminophen (APAP) overdose is the predominant cause of acute liver failure in
      the United States. Toxicity begins with a reactive metabolite that binds to
      proteins. In rodents, this leads to mitochondrial dysfunction and nuclear DNA
      fragmentation, resulting in necrotic cell death. While APAP metabolism is similar
      in humans, the later events resulting in toxicity have not been investigated in
      patients. In this study, levels of biomarkers of mitochondrial damage (glutamate
      dehydrogenase [GDH] and mitochondrial DNA [mtDNA]) and nuclear DNA fragments were
      measured in plasma from APAP-overdose patients. Overdose patients with no or
      minimal hepatic injury who had normal liver function tests (LTs) (referred to
      herein as the normal LT group) and healthy volunteers served as controls. Peak
      GDH activity and mtDNA concentration were increased in plasma from patients with
      abnormal LT. Peak nuclear DNA fragmentation in the abnormal LT cohort was also
      increased over that of controls. Parallel studies in mice revealed that these
      plasma biomarkers correlated well with tissue injury. Caspase-3 activity and
      cleaved caspase-3 were not detectable in plasma from overdose patients or mice,
      but were elevated after TNF-induced apoptosis, indicating that APAP overdose does
      not cause apoptosis. Thus, our results suggest that mitochondrial damage and
      nuclear DNA fragmentation are likely to be critical events in APAP hepatotoxicity
      in humans, resulting in necrotic cell death.

PMID- 22378044
TI  - beta1Integrin/FAK/cortactin signaling is essential for human head and neck cancer
      resistance to radiotherapy.
AB  - Integrin signaling critically contributes to the progression, growth, and therapy
      resistance of malignant tumors. Here, we show that targeting of beta1 integrins
      with inhibitory antibodies enhances the sensitivity to ionizing radiation and
      delays the growth of human head and neck squamous cell carcinoma cell lines in 3D
      cell culture and in xenografted mice. Mechanistically, dephosphorylation of focal
      adhesion kinase (FAK) upon inhibition of beta1 integrin resulted in dissociation
      of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling
      and induced cell rounding, leading to radiosensitization. Thus, these findings
      suggest that robust and selective pharmacological targeting of beta1 integrins
      may provide therapeutic benefit to overcome tumor cell resistance to
      radiotherapy.

PMID- 22378045
TI  - P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the
      expression of TIMP3.
AB  - Malignant gliomas are the most common and the most lethal primary brain tumors in
      adults. Among malignant gliomas, 60%-80% show loss of P14ARF tumor suppressor
      activity due to somatic alterations of the INK4A/ARF genetic locus. The tumor
      suppressor activity of P14ARF is in part a result of its ability to prevent the
      degradation of P53 by binding to and sequestering HDM2. However, the subsequent
      finding of P14ARF loss in conjunction with TP53 gene loss in some tumors suggests
      the protein may have other P53-independent tumor suppressor functions. Here, we
      report what we believe to be a novel tumor suppressor function for P14ARF as an
      inhibitor of tumor-induced angiogenesis. We found that P14ARF mediates
      antiangiogenic effects by upregulating expression of tissue inhibitor of
      metalloproteinase-3 (TIMP3) in a P53-independent fashion. Mechanistically, this
      regulation occurred at the gene transcription level and was controlled by HDM2
      SP1 interplay, where P14ARF relieved a dominant negative interaction of HDM2 with
      SP1. P14ARF-induced expression of TIMP3 inhibited endothelial cell migration and
      vessel formation in response to angiogenic stimuli produced by cancer cells. The
      discovery of this angiogenesis regulatory pathway may provide new insights into
      P53-independent P14ARF tumor-suppressive mechanisms that have implications for
      the development of novel therapies directed at tumors and other diseases
      characterized by vascular pathology.

PMID- 22378046
TI  - Tradition, tradition.

PMID- 22378048
TI  - Synergistic effects of erlotinib and everolimus on bronchial carcinoids and large
      cell neuroendocrine carcinomas with activated EGFR/AKT/mTOR pathway.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) and mammalian target of
      rapamycin (mTOR) are crucial targets in cancer therapy. Combined inhibition of
      both targets yielded synergistic effects in vitro and in vivo in several cancer
      entities. However, the impact of EGFR and mTOR expression and combined inhibition
      in neuroendocrine lung tumors other than small-cell lung cancer remains unclear.
      MATERIAL AND METHODS: Expression and activation of EGFR/AKT/mTOR pathway
      constituents were investigated in typical and atypical bronchial carcinoid (AC)
      tumors and large-cell neuroendocrine lung carcinomas (LCNEC) by
      immunohistochemistry in 110 tumor samples, and correlated with
      clinicopathological parameters and patient survival. Cytotoxicity of mTOR
      inhibitor everolimus and EGFR inhibitor erlotinib alone and in combination was
      assessed using growth inhibition assay in NCI-H720 AC and SHP-77 LCNEC cells.
      Cell cycle phase distribution was determined by FACS. Apoptosis-associated
      activation of caspase-3/7 was measured by Caspase-Glo(r) assay. Activity status
      of EGFR and mTOR pathway components was analyzed by immunoblotting. RESULTS:
      Activation of the EGFR/AKT/mTOR axis could be demonstrated in all entities and
      was significantly increased in higher grade tumors. Neoadjuvant chemotherapy
      correlated significantly with p-AKT expression and p-ERK loss. Erlotinib combined
      with everolimus exerted synergistic combination effects in AC and LCNEC cells by
      induction of apoptosis, while cell cycle phase distribution remained unaffected.
      These effects could be explained by synergistic downregulation of phospho-mTOR,
      phospho-p70S6 kinase and phospho-AKT expression by everolimus and erlotinib.
      CONCLUSIONS: Our study indicates that EGFR and mTOR are clinically important
      targets in bronchial neuroendocrine tumors, and further in vivo and clinical
      exploration of combined inhibition is warranted.

PMID- 22378049
TI  - Neural remodeling and ventricular arrhythmias: understanding the mechanism.

PMID- 22378047
TI  - Macrophage plasticity and polarization: in vivo veritas.
AB  - Diversity and plasticity are hallmarks of cells of the monocyte-macrophage
      lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13
      signaling, macrophages undergo M1 (classical) or M2 (alternative) activation,
      which represent extremes of a continuum in a universe of activation states.
      Progress has now been made in defining the signaling pathways, transcriptional
      networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized
      activation. Functional skewing of mononuclear phagocytes occurs in vivo under
      physiological conditions (e.g., ontogenesis and pregnancy) and in pathology
      (allergic and chronic inflammation, tissue repair, infection, and cancer).
      However, in selected preclinical and clinical conditions, coexistence of cells in
      different activation states and unique or mixed phenotypes have been observed, a
      reflection of dynamic changes and complex tissue-derived signals. The
      identification of mechanisms and molecules associated with macrophage plasticity
      and polarized activation provides a basis for macrophage-centered diagnostic and
      therapeutic strategies.

PMID- 22378050
TI  - Measurement of 129Xe gas apparent diffusion coefficient anisotropy in an elastase
      instilled rat model of emphysema.
AB  - Hyperpolarized noble gas ((3)He and (129)Xe) apparent diffusion coefficient (ADC)
      measurements have shown remarkable sensitivity to microstructural (i.e.,
      alveolar) changes in the lung, particularly emphysema. The ADC of hyperpolarized
      noble gases depends strongly on the diffusion time (Delta), and (3)He ADC has
      been shown to be anisotropic for Delta ranging from a few milliseconds down to a
      few hundred microseconds. In this study, the anisotropic nature of (129)Xe
      diffusion and its dependence on Delta were investigated both numerically, in a
      budded cylinder model, and in vivo, in an elastase-instilled rat model of
      emphysema. Whole lung longitudinal ADC (D(L)) and transverse ADC (D(T)) were
      measured for Delta = 6, 50, and 100 ms at 73.5 mT, and correlated with
      measurements of the mean linear intercept (L(m)) obtained from lung histology. A
      significant increase (P = 0.0021) in D(T) was measured for Delta = 6 ms between
      the sham (0.0021 +/- 0.0005 cm(2)/s) and elastase-instilled (0.005 +/- 0.001
      cm(2)/s) cohorts, and a strong correlation was measured between D(T) (Delta = 6
      ms) and L(m), with a Pearson's correlation coefficient of 0.90. This study
      confirms that (129)Xe D(T) increases correlate with alveolar space enlargement
      due to elastase instillation in rats.

PMID- 22378051
TI  - Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial
      Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo
      controlled clinical trial.
AB  - Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO)
      were included in this blinded clinical study and randomly assigned to one of two
      treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4
      mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General
      anesthesia was maintained with isoflurane in oxygen and a constant rate infusion
      (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on
      changes in physiological parameters and on the analgesics requirement, whereas in
      the post-operative period evaluation of pain was performed by using a Hellyer and
      Gaynor pain score and by comparing the doses of rescue buprenorphine required by
      the two treatment groups. Although no statistically significant differences in
      intra-operative sufentanyl doses were found between treatment groups, group C had
      superior cardiovascular stability, and lower post-operative pain scores and
      rescue buprenorphine doses than group P. Our results indicate that administration
      of carprofen prior to surgery was effective in improving peri-operative analgesia
      in dogs undergoing TPLO.

PMID- 22378052
TI  - [First results on the mandatory notification of dog bite injuries in Switzerland:
      a questionnaire survey among physicians and veterinarians].
AB  - In order to expedite targeted interventions, mandatory notification of treated
      dog bite injuries for Swiss physicians and veterinarians was implemented in 2006.
      Since the number of notified cases was much lower than expected, the validity of
      the annually produced statistics with respect to the real situation in
      Switzerland was discussed controversially. In this study a questionnaire survey
      among physicians and veterinarians was carried out to evaluate the amount of and
      reasons for non-compliance with the mandatory notification. 81 % of the
      physicians and 97 % of the veterinarians reported the treatment of dog bite
      injuries in the year 2009. Among those, 60 % of the physicians and 41 % of the
      veterinarians indicated notification of less than 50 % of the treated cases. Our
      results indicate that the most relevant cases for targeted interventions seem to
      be notified, but that the statistical analyses have to be interpreted carefully.

PMID- 22378053
TI  - Bilateral congenital lacrimal fistula in a Brown Swiss bull.
AB  - A five-year-old Brown Swiss bull was referred to the Department of Farm Animals,
      University of Zurich, because of bilateral epiphora that was unresponsive to
      treatment. Clinical examination revealed a fistulous opening medial to the medial
      canthus of both eyes and mucopurulent discharge from both openings. Attempts to
      flush the nasolacrimal duct via the lacrimal points resulted in the fluid exiting
      via the fistulous opening. Retrograde flushing of the nasolacrimal duct from the
      nasolacrimal opening resulted in the flush fluid flowing back out the
      nasolacrimal opening. Bilateral lacrimal fistula medial to the medial canthus of
      the eye was diagnosed based on the findings. The same anomaly was diagnosed a
      year later in 4 related female animals referred to our Department for other
      reasons. Three of the cases were sired by the bull described above and one was
      sired by his half-brother. Therefore, an autosomal recessive mode of inheritance
      of this anomaly was assumed. Clinical, epidemiological and molecular studies of
      the offspring of both bulls are underway to further investigate this anomaly.

PMID- 22378054
TI  - [RadioSurfVet--an E-learning program for support of self-study in the module
      "General Radiology" for studying veterinary medicine in the 1st year].

PMID- 22378055
TI  - Antibiotic treatments of a methicillin-resistant Staphylococcus pseudintermedius
      infection in a dog: a case presentation.

PMID- 22378057
TI  - [Short-term work release].

PMID- 22378059
TI  - Intraepidermal neutrophilic IgA pemphigus successfully treated with dapsone.

PMID- 22378060
TI  - Metal-organic frameworks for the storage and delivery of biologically active
      hydrogen sulfide.
AB  - Hydrogen sulfide is an extremely toxic gas that is also of great interest for
      biological applications when delivered in the correct amount and at the desired
      rate. Here we show that the highly porous metal-organic frameworks with the CPO
      27 structure can bind the hydrogen sulfide relatively strongly, allowing the
      storage of the gas for at least several months. Delivered gas is biologically
      active in preliminary vasodilation studies of porcine arteries, and the structure
      of the hydrogen sulfide molecules inside the framework has been elucidated using
      a combination of powder X-ray diffraction and pair distribution function
      analysis.

PMID- 22378063
TI  - Amidetriazole: a versatile building block for construction of oxyanion anion
      receptors.
AB  - The design and synthesis of efficient receptors for tetrahedral oxyanions is an
      emerging field in supramolecular chemistry. Herein, we have developed a urea-like
      anion-recognizing motif, amidetriazole, which can be easily synthesized and
      derived and shows good solubility. A series of simple acyclic receptors were
      designed and synthesized to confirm the potential of amidetriazole for the
      construction of tetrahedral oxyanion receptors. This molecular platform can be
      used extensively for the construction of numerous receptor systems appended with
      functional groups, which opens the way to many applications in the field of
      supramolecular chemistry.

PMID- 22378062
TI  - Psychiatric side effects and fluctuations in serotonergic parameters in the
      treatment of chronic hepatitis C infection.
AB  - INTRODUCTION: Treatment of hepatitis C with peginterferon induces psychiatric
      side effects. These might include changes in serotonergic function. METHODS:
      Twenty-two hepatitis C patients were treated with peginterferon. At different
      time points, psychometric assessment was performed using the profile of mood
      states. Plasma samples were taken to study serotonergic parameters. RESULTS:
      Anger and depression increased compared to baseline, starting with anger (from
      week 3 onwards), followed by depression (from week 7 onwards). Other scores did
      not show consistent changes. No consistent changes were observed in tryptophan,
      tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic
      acid. The tyrosine/large neutral amino acids ratio, neopterin,
      phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to
      baseline. Prolactin levels were associated with the occurrence of depression and
      anger. DISCUSSION: Particularly anger and depression increased during treatment.
      Neither a decrease in tryptophan and tryptophan availability was seen, nor a
      relationship between these parameters and the development of psychopathology.
      Therefore, other mechanisms in the induction of psychopathology should be
      considered. The observed increases in neopterin and phenylalanine/tyrosine ratio
      are indicative of changes in tetrahydrobiopterin, which is involved in the
      metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the
      increase in prolactin. The increase in prolactin levels and its relationship with
      depression and anger needs further exploration.

PMID- 22378061
TI  - Chronic inflammation, immune escape, and oncogenesis in the liver: a unique
      neighborhood for novel intersections.
AB  - Sustained hepatic inflammation, driven by alcohol consumption, nonalcoholic fatty
      liver disease, and/or chronic viral hepatitis (hepatitis B and C), results in
      damage to parenchyma, oxidative stress, and compensatory
      regeneration/proliferation. There is substantial evidence linking these
      inflammation-associated events with the increased incidence of hepatocellular
      carcinogenesis. Although acute liver inflammation can play a vital and beneficial
      role in response to liver damage or acute infection, the effects of chronic liver
      inflammation, including liver fibrosis and cirrhosis, are sufficient in a
      fraction of individuals to initiate the process of transformation and the
      development of hepatocellular carcinoma. This review highlights immune-dependent
      mechanisms that may be associated with hepatocellular oncogenesis, including
      critical transformative events/pathways in the context of chronic inflammation
      and subverted tolerogenesis.

PMID- 22378064
TI  - A novel nanoaggregation detection technique of TNT using selective and
      ultrasensitive nanocurcumin as a probe.
AB  - Here, for the first time, we designed an ultrasensitive nanocurcumin based
      nanomaterials surface energy transfer (NSET) probe for detection of trace amount
      of TNT with excellent sensitivity (1 nM) and selectivity over other nitro
      explosives via nanoaggregation and we found the largest fluorescent enhancement
      to date for sensing TNT (upto 800 fold).

PMID- 22378066
TI  - Radiosensitizing effect of 5-aminolevulinic acid-induced protoporphyrin IX in
      glioma cells in vitro.
AB  - 5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy and
      fluorescence-guided resection of malignant gliomas due to its high cellular
      uptake in tumours. Porphyrin compounds act not only as photosensitizers but also
      as radiosensitizers. In the present study, the possible use of 5-ALA as a
      radiosensitizer for malignant gliomas was examined in vitro. Rat glioma cell
      lines (9L, C6) were pre-treated with 5-ALA and exposed to ionizing irradiation.
      The radiosensitizing effect of 5-ALA was evaluated by colony-forming assay.
      Intracellular reactive oxygen species (ROS) produced by 5-ALA and irradiation
      were evaluated by confocal laser scanning microscopy. Pre-treatment with 5-ALA
      enhanced the radiosensitivity of 9L cells to single-dose ionizing irradiation
      compared with controls (D0 value, 4.35 +/- 0.20 and 4.84 +/- 0.23 Gy,
      respectively, P <= 0.05). Exposure to multi-dose ionizing irradiation revealed
      high radiosensitivity in both 9L and C6 cells pre-treated with 5-ALA compared to
      controls. Production of intracellular ROS increased in 9L cells pre-treated with
      5-ALA after ionizing irradiation compared to control cells. Thus, 5-ALA functions
      as a specific radiosensitizer for malignant gliomas. Intracellular 5-ALA-induced
      PpIX plays an important role in the production of ROS and the radiosensitizing
      effect under ionizing irradiation conditions.

PMID- 22378065
TI  - Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the beta1
      integrin-RACK1 axis.
AB  - Trop-2 is a transmembrane glycoprotein upregulated in several human carcinomas,
      including prostate cancer (PrCa). Trop-2 has been suggested to regulate cell-cell
      adhesion, given its high homology with the other member of the Trop family, Trop
      1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and
      claudin-7. However, a role for Trop-2 in cell adhesion to the extracellular
      matrix has never been postulated. Here, we show for the first time that Trop-2
      expression in PrCa cells correlates with their aggressiveness. Using either shRNA
      mediated silencing of Trop-2 in cells that endogenously express it, or ectopic
      expression of Trop-2 in cells that do not express it, we show that Trop-2
      inhibits PrCa cell adhesion to fibronectin (FN). In contrast, expression of
      another transmembrane receptor, alpha(v) beta(5) integrin, does not affect cell
      adhesion to this ligand. We find that Trop-2 does not modulate either protein or
      activation levels of the prominent FN receptors, beta(1) integrins, but acts
      through increasing beta(1) association with the adaptor molecule RACK1 and
      redistribution of RACK1 to the cell membrane. As a result of Trop-2 expression,
      we also observe activation of Src and FAK, known to occur upon beta(1) -RACK1
      interaction. These enhanced Src and FAK activities are not mediated by changes in
      either the activity of IGF-IR, which is known to bind RACK1, or IGF-IR's ability
      to associate with beta(1) integrins. In summary, our data demonstrate that the
      transmembrane receptor Trop-2 is a regulator of PrCa cell adhesion to FN through
      activation of the beta(1) integrin-RACK1-FAK-Src signaling axis.

PMID- 22378068
TI  - Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition
      of mTOR pathway and induction of autophagy.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) acts as a major sensor of
      cellular energy status in cancers and is critically involved in cell sensitivity
      to anticancer agents. Here, we showed that AMPK was inactivated in lymphoma and
      related to the upregulation of the mammalian target of rapamycin (mTOR) pathway.
      AMPK activator metformin potentially inhibited the growth of B- and T-lymphoma
      cells. Strong antitumor effect was also observed on primary lymphoma cells while
      sparing normal hematopoiesis ex vivo. Metformin-induced AMPK activation was
      associated with the inhibition of the mTOR signaling without involving AKT.
      Moreover, lymphoma cell response to the chemotherapeutic agent doxorubicin and
      mTOR inhibitor temsirolimus was significantly enhanced when co-treated with
      metformin. Pharmacologic and molecular knock-down of AMPK attenuated metformin
      mediated lymphoma cell growth inhibition and drug sensitization. In vivo,
      metformin induced AMPK activation, mTOR inhibition and remarkably blocked tumor
      growth in murine lymphoma xenografts. Of note, metformin was equally effective
      when given orally. Combined treatment of oral metformin with doxorubicin or
      temsirolimus triggered lymphoma cell autophagy and functioned more efficiently
      than either agent alone. Taken together, these data provided first evidence for
      the growth-inhibitory and drug-sensitizing effect of metformin on lymphoma.
      Selectively targeting mTOR pathway through AMPK activation may thus represent a
      promising new strategy to improve treatment of lymphoma patients.

PMID- 22378070
TI  - Aspirin-exacerbated asthma: avoiding challenge is still challenging.

PMID- 22378069
TI  - Raf kinases mediate the phosphorylation of eukaryotic translation elongation
      factor 1A and regulate its stability in eukaryotic cells.
AB  - We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated
      phosphorylation sites and defined their role in the regulation of eEF1A half-life
      and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21
      and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1
      whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21
      belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of
      S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the
      assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus
      increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in
      COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt,
      in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D)
      mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less
      stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A
      mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It
      indicates that the blockage of S21 interferes with or even supports C-Raf induced
      apoptosis rather than cell survival. Raf-mediated regulation of this site could
      be a crucial mechanism involved in the functional switching of eEF1A between its
      role in protein biosynthesis and its participation in other cellular processes.

PMID- 22378071
TI  - Macrophage inflammatory protein-1beta and fibrinogen are synergistic predictive
      markers of prognosis of intermediate coronary artery lesions.
AB  - OBJECTIVE: We tested the hypothesis that the plasma levels of fibrinogen and
      macrophage inflammatory protein (MIP)-1beta are synergistic predictive markers of
      the prognosis of intermediate coronary artery lesions. METHODS: A prospective
      study was performed on 670 patients with intermediate coronary artery lesions.
      Fibrinogen and MIP-1beta were measured. Major adverse cardiac event (MACE) was
      defined as a composite of cardiovascular death, nonfatal myocardial infarction,
      revascularization and readmission due to angina pectoris. RESULTS: During follow
      up, 72 events occurred; 5 patients died, 7 patients suffered a nonfatal
      myocardial infarction, 11 patients underwent revascularization and 49 patients
      were readmitted for angina pectoris. In patients with above-median levels of MIP
      1beta, a 2.62-fold risk of a MACE [95% confidence interval (CI) 1.53-4.48] was
      predicted compared with patients with below-median levels of MIP-1beta. However,
      the strongest risk prediction was achieved by assessing MIP-1beta and fibrinogen
      together. After adjusting for traditional risk factors, a multivariate Cox
      proportional hazards analysis showed that patients with both MIP-1beta and
      fibrinogen above the median had a 4.37-fold risk of a MACE (95% CI 1.89-10.11).
      CONCLUSION: MIP-1beta accurately predicted MACEs. Considering MIP-1beta and
      fibrinogen together may improve long-term risk assessment. These two biomarkers
      have a synergistic effect for assessing long-term risk in patients with
      intermediate coronary artery lesions.

PMID- 22378072
TI  - Immunomarkers in gynecologic cytology: the search for the ideal 'biomolecular
      Papanicolaou test'.
AB  - Harnessing the knowledge we have gained on the cell cycle disruption caused by
      human papillomaviruses (HPV) will likely lead to improved screening modalities
      for cervical cancer and its precursors. An easily applied biomarker that has high
      specificity and sensitivity would represent an attractive alternative or
      complement to cytology and HPV testing. To date, a number of promising markers
      have been investigated. These include p16(INK4A), MIB-1, BD-ProEx C, and L1.
      Newer possibilities involve a variety of gene products associated with
      aberrations of chromosome 3q, such as telomerase, p63, and PIK3CA, as well the
      combination of biomarkers such as p16(INK4A) and MIB-1 in the same assay.
      Although none of them has yet been incorporated into screening algorithms or
      found its way into routine practice, their performance characteristics remain a
      focus of current investigations. This review summarizes what we know and where we
      hope to go in translating basic pathobiology into clinical practice.

PMID- 22378073
TI  - Reclassifying formerly indeterminate thyroid FNAs using the Bethesda system
      reduces the number of inconclusive cases.
AB  - OBJECTIVE: To evaluate the effectiveness of the Bethesda System for Reporting
      Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses
      following BSRTC adoption. STUDY DESIGN: According to the BSRTC, we reclassified
      cytologic samples originally diagnosed as 'indeterminate' with sequential
      surgical resection. Then, we analyzed the causes of cases, which were
      recategorized as 'atypia undetermined significance/follicular lesion of
      undetermined significance (AUS/FLUS)'. RESULTS: According to the BSRTC, 154
      'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%);
      benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular
      neoplasm, n = 7 (7.1%); suspicious for a Hurthle cell neoplasm, n = 4 (2.6%);
      suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the
      AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC.
      Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In
      addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused
      inconclusive diagnoses. CONCLUSION: The BSRTC can be easily applied to thyroid
      fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules
      into more detailed categories and thus reduce the number of cases classified as
      indeterminate. However, suboptimal preparation, papillary microcarcinoma, and
      coexisting Hashimoto's thyroiditis precluded cytopathologists from making
      definitive diagnoses.

PMID- 22378074
TI  - Fine-needle cytology and flow cytometry assessment of reactive and
      lymphoproliferative processes of the breast.
AB  - OBJECTIVE: The breast may be affected by reactive and lymphoproliferative
      processes such as primary (PBL) or secondary (SBL) lymphoma, reactive
      intramammary lymph nodes and sclerosing lobulitis; imaging may be not specific
      and surgical treatment not indicated. We report an experience with fine-needle
      cytology (FNAC) combined with flow cytometry (FC) and immunocytochemistry (ICC)
      in the diagnosis of these processes. STUDY DESIGN: Thirty-seven cases comprising
      intramammary lymph nodes (n = 15), sclerosing lobulitis (n = 2), PBL (n = 11) and
      SBL (n = 9) are reported. FNAC was used to prepare traditional smears,
      conventional ICC or FC. Cytological diagnoses were compared to the imaging data,
      checked by histology or follow-up and statistically evaluated. RESULTS: Imaging
      was not conclusive in most PBL, SBL, sclerosing lobulitis and some intramammary
      lymph nodes. FNAC combined with FC and ICC provided a definitive diagnosis of
      intramammary lymph node, sclerosing lobulitis, PBL and SBL in 18 cases with
      indication of the specific subtype in 10 cases. Statistical analysis showed 90%
      sensitivity, 100% specificity, 100% positive predictive value and 89% negative
      predictive value. CONCLUSIONS: FNAC combined with FC and ICC is a helpful
      procedure for the diagnosis of reactive and lymphoproliferative processes of the
      breast. It may prevent unnecessary biopsy and speed up therapeutic procedures.

PMID- 22378075
TI  - The role of axillary lymph node fine needle aspiration in breast cancer staging
      prior to chemotherapy with histological correlation.
AB  - OBJECTIVE: Axillary lymph node (LN) sampling is important for breast cancer
      staging and can be performed using fine needle aspiration (FNA). The aim of this
      study is to review the axillary LN FNAs performed at our institution prior to
      treatment, and to correlate their results with the available LN histology in
      order to evaluate the diagnostic utility of FNA. STUDY DESIGN: A total of 130
      cases were retrospectively identified over a 1-year period and reviewed. The FNA
      findings were correlated with the histological findings in 65 (50%) LN core
      biopsies, 43 (33%) sentinel LN biopsies, and 22 (17%) axillary dissections.
      RESULTS: One hundred and thirteen FNA cases (89%) correlated with the histology,
      while 14 cases (11%) did not correlate, including 1 false positive and 13 false
      negatives. Of the false-negative cases, metastases in the biopsy ranged from
      isolated tumor cells to 5 mm in the greatest dimension. The overall sensitivity
      was 85%, specificity 98%, positive predictive value 99%, and negative predictive
      value 75%. CONCLUSION: Pretherapy staging of breast cancer by FNA is a useful
      diagnostic modality with a high specificity and positive predictive value. Due to
      false-negative diagnoses, a negative FNA should be followed up with further LN
      sampling.

PMID- 22378076
TI  - Ultrasound gel causes fine needle aspiration artifact? A clear choice.
AB  - OBJECTIVES: Ultrasound-guided fine needle aspiration (FNA) is a commonly employed
      tool in cytopathologic practice. Artifacts resulting in misinterpretation of
      specimens have been noted with various ultrasound gel media. Our purpose was to
      perform a prospective human cadaveric study of this phenomenon to identify a low
      cost solution that eliminates the artifact. STUDY DESIGN: Three separate
      ultrasound-guided FNAs were performed on the thyroid and parotid glands in situ
      of a fresh human cadaver using three different types of ultrasound gel media.
      Slides were prepared in standard fashion (Quik-Diff and Papanicolaou stains). Two
      cytopathologists subsequently analyzed the slides for the presence of any
      artifact interfering with their ability to visualize and interpret the cellular
      aspirate material. RESULTS: Two of the three gel media revealed significant
      artifacts mimicking apoptosis, necrosis or colloid, making it difficult to
      visualize the cellular components and differentiate the artifact from the thyroid
      colloid. One gel medium did not show any significant artifact, and there was no
      discernable difference in its quality with regard to the ultrasound image during
      FNA procedures. CONCLUSIONS: Ultrasound gels can be associated with a significant
      artifact in FNA specimens. To eliminate this artifact, which may alter the
      adequacy, diagnosis or cytologic appearance, we confirm a specific gel type that
      is useful for ultrasound-guided FNAs.

PMID- 22378077
TI  - Type-specific human papillomavirus DNA detected in atypical glandular cell Pap
      tests.
AB  - OBJECTIVES: To evaluate the presence of type-specific human papillomavirus (HPV)
      DNA in atypical glandular cells (AGCs) from cervical liquid-based cytology and to
      report the relationship between HPV types and cervical histological
      abnormalities. STUDY DESIGN: We used a nested multiplex polymerase chain reaction
      assay to test AGC Papanicolaou (Pap) tests for the presence of 14 high-risk (HR)
      HPV types. RESULTS: HR HPV types were detected in 33 of 161 AGC Pap tests
      (20.3%). Types 16 and/or 18 were detected in 13 samples (8%). Eight other HPV
      types were detected in 1-4 samples each. HPV-associated disease was diagnosed in
      8 AGC cases (8%) with available histology results. The sensitivity and
      specificity of the HR HPV test were 87.5 and 90%, respectively, and the negative
      predictive value (NPV) was 99%. For a test that can isolate HPV types 16 and 18,
      the sensitivity and specificity were 62.5 and 100%, respectively, the positive
      predictive value (PPV) was 100% and the NPV was 97%. CONCLUSION: HPV 16 and 18
      were the most common types detected in AGC Paps. We found high specificity, PPV
      and NPV with a test that can isolate these 2 HPV types. These results indicate a
      possible role for type-specific HPV testing in the management of AGC Pap tests.

PMID- 22378078
TI  - Implementing human papillomavirus testing in a public health hospital: challenges
      and opportunities.
AB  - OBJECTIVES: Robust evidence now supports human papillomavirus (HPV) testing as a
      more effective option to screening and as more sensitive than cytology in
      detecting high-grade cervical intraepithelial neoplasia . Our goal was to analyze
      the performance of the Hybrid Capture II (HC2) assay for high-risk HPV (hrHPV) in
      women undergoing gynecological examination at a public health hospital as part of
      the evaluation of HPV screening as an alternative or complement to cytology.
      STUDY DESIGN: This analysis is a subset of a cross-sectional study carried out at
      a large public hospital serving a predominantly low-resource population. A total
      of 705 women were enrolled; the sensitivity and specificity of each test were
      estimated and compared. RESULTS: The analysis identified 272 hrHPV-positive women
      (mean age 36.3 years) and 433 hrHPV-negative women (mean age 41.2 years). HPV
      testing showed a significantly increased sensitivity of the HC2 assay versus
      cytology (84.5 vs. 69.7%; p < 0.0001) but a lower specificity (49.90 vs. 88.78%;
      p < 0.0001). CONCLUSION: The combination of both methods seems to be useful in
      improving detection of cervical lesions.

PMID- 22378079
TI  - Diagnostic utility of notch-1 immunocytochemistry in endometrial cytology.
AB  - OBJECTIVE: It was the aim of this study to evaluate the diagnostic utility of
      Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal
      breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology. STUDY
      DESIGN: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were
      subjected to immunocytochemical staining for Notch-1, and we examined the
      labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells
      to total cells). We compared (1) the Notch-1 LI in normal endometrium, (2) the
      Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the
      Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma. RESULTS:
      In analysis item 1, the LI of Notch-1 was 32.9 +/- 8.4, 19.4 +/- 8.2 and 12.5 +/-
      7.5% in proliferative endometrium, secretory endometrium and atrophic
      endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial
      adenocarcinoma was 45.2 +/- 7.4%, which was significantly higher than that in
      normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 +/-
      8.3%, which was significantly lower than that in endometrial adenocarcinoma.
      CONCLUSION: In conclusion, Notch-1 immunocytochemistry is a useful method for
      distinguishing between EGBD and endometrial carcinoma in endometrial cytology.

PMID- 22378080
TI  - Cytomorphological analysis of uterine cervical pap smears in relation to human
      papillomavirus infection in Indonesian women.
AB  - OBJECTIVE: Cervical cancer is the number one cause of cancer-associated death in
      Indonesian women (30/100,000 annually), where no screening program is present.
      The Papanicolaou test is widely accepted as an effective screening method for
      cervical neoplasia detection and often shows certain cytological features
      associated with human papillomavirus (HPV) infection. Especially in developing
      countries, cytological investigation is still the method of choice as compared to
      the frequent use of HPV DNA testing in western countries. STUDY DESIGN: In the
      present study, we investigated the validity of the use of cytomorphological
      changes as a marker for HPV infection. A total of 140 smears collected in three
      different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV
      DNA testing was performed using INNO-LiPA assays. RESULTS AND CONCLUSIONS: We
      found a highly significant association of classical koilocytosis, multinucleated
      cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei,
      moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using
      classical and nonclassical cytomorphological parameters we found an overall
      sensitivity of 42% and a specificity of 90%. The combination of classical and
      nonclassical parameters led to a higher sensitivity of HPV positivity prediction.
      These results are of importance for cytologists in developing countries as
      molecular HPV testing still poses a major financial, logistic and expertise
      problem.

PMID- 22378081
TI  - Signet ring cell carcinoma in urine cytology: cytomorphologic findings and
      differential diagnosis.
AB  - BACKGROUND: Signet ring carcinoma is an exceedingly rare and aggressive variant
      of primary bladder carcinoma. The cytomorphologic features of this rare entity in
      urinary specimens have not been well characterized. METHODS: Twenty-seven cases
      of signet ring cell carcinoma of the urinary bladder were identified from the
      pathology archives of The Johns Hopkins Hospital (1989-2011). Of these, 6 cases
      with prior urinary cytology specimens were studied. RESULTS: There were 5 males
      and 1 female, with a mean age of 62 years. The presenting complaints included
      hematuria with or without symptoms of bladder irritation. Histopathologically,
      there were 5 cases of primary bladder carcinoma and 1 case of metastatic colonic
      signet ring cell carcinoma. The salient cytomorphologic features included
      scattered malignant epithelial cells, displaying distinct cell borders, abundant
      cytoplasm with a single large, discrete mucin vacuole, and eccentric irregular
      nuclei with prominent nucleoli. Primary adenocarcinoma additionally revealed a
      few intact malignant glandular epithelial fragments. Metastatic colonic signet
      ring cell carcinoma displayed predominantly singly dispersed malignant cells with
      eccentrically placed, oval nuclei with occasional small nucleoli and a moderate
      amount of vacuolated cytoplasm. CONCLUSION: Signet ring cell carcinomas are
      rarely encountered in urinary cytology. The differential diagnosis includes
      distended histiocytes or degenerated urothelial cells, primary signet ring cell
      carcinoma, and metastatic adenocarcinoma.

PMID- 22378082
TI  - Analysis of squash smear cytology of ependymomas.
AB  - BACKGROUND: Ependymomas constitute 8-10 and 1-3% of central nervous system tumors
      in children and adults, respectively. Though intraoperative squash smear cytology
      is well documented, grading is rarely described. OBJECTIVES: (1) To assess
      cytomorphology and grade ependymomas in squash smears. (2) To compare utility of
      hematoxylin and eosin (H&E) and toluidine blue (TB) staining. STUDY DESIGN:
      Ependymomas diagnosed from 2004 to 2010 were retrieved from pathology records.
      Intraoperative squash smears stained with TB and H&E were studied. RESULTS:
      Histological sections of 29 ependymomas were graded according to WHO 2007
      classification. There were 3 myxopapillary (grade I), 13 grade II, and 13 grade
      III (anaplastic) ependymomas. Perivascular pseudorosettes were seen in 23 smears,
      and 11 showed rosettes. Less cohesive cells at the periphery of fragments with
      unipolar cytoplasmic processes were seen in all smears. The background was
      fibrillary in all except in myxopapillary ependymoma. Metachromatic material was
      seen in myxopapillary ependymoma around vessels and in globi. The nucleus was
      round with stippled chromatin and 1-2 small nucleoli could be seen. All smears of
      grade III ependymomas showed pleomorphism, mitoses, microvascular proliferation
      and necrosis. CONCLUSION: Ependymomas can be diagnosed and graded reliably by
      squash smear. Myxoid stroma was better appreciated by TB staining. TB and H&E
      complement each other in squash smears for cytomorphology.

PMID- 22378083
TI  - Discriminant analysis of malignant mesothelioma and reactive mesothelium using
      three-dimensional nuclear estimation.
AB  - OBJECTIVE: The cytological diagnosis of coelomic fluid is essential for examining
      malignant mesothelioma (MM). However, reactive mesothelium (RM), caused by
      various factors, is morphologically similar to MM and thus often complicates the
      differential diagnosis. Here, nuclear luminance and steric alterations were
      assessed for the discriminant analysis of MM and RM. STUDY DESIGN: Thirteen
      epithelial MM and 11 RM cases were included. One hundred alterations in the
      numbers of nuclear pixels and focus layers and the coefficient of variation of
      nuclear luminance among layers were determined for each case to conduct
      discriminant analysis using the Mahalanobis distance. RESULTS: A cutoff value of
      0.072 allowed highly accurate discrimination of MM (89.5%) and RM (89.6%).
      Fifteen cells appeared in 6 agglomerates of indiscriminable MM cases. The 6
      agglomerates were individually examined. Malignant cells were dominant in 3
      agglomerates (50%), allowing the discrimination of malignant cases. CONCLUSION:
      Discrimination using nuclear luminance and steric alterations is useful for
      morphologically indiscriminable MM cases. Three-dimensional analysis of
      agglomerates will be further investigated to improve the diagnostic accuracy.

PMID- 22378084
TI  - Assessment of fine needle aspiration specimen adequacy for high-risk HPV
      detection and genotyping in oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to determine the adequacy of archived and
      fresh fine needle aspiration (FNA) specimens from metastatic head and neck
      squamous cell carcinoma (SCC) for the molecular detection and genotyping of high
      risk (HR) HPV. STUDY DESIGN: Thirty-seven specimens from 26 patients diagnosed by
      FNA with metastatic SCC were included as retrospective specimens [19 slides
      stained with Papanicolaou (Pap) and 18 with Diff-Quik(r) (DQ)]. Twenty fresh FNA
      specimens from 18 patients were included as prospective specimens. These
      specimens were analyzed using the standard protocol for ThinPrep(r) cervical
      specimens, with a Cervista HR HPV detection kit. The positive specimens were
      tested for the HPV 16 and 18 genotypes. RESULTS: Forty-four of 57 specimens (77%)
      had sufficient cells to yield a valid HPV result. The adequacy rate for Pap
      stained slides was 15/19 (79%), for DQ-stained slides it was 13/18 (72%), and for
      fresh needle aspirates it was 16/20 (80%). HR HPV was detected in 23/44 (52%)
      specimens. Among the 23 HPV-positive specimens, 19 were genotyped as HPV 16 and 1
      as HPV 18. CONCLUSIONS: HR HPV detection and genotyping can be performed on FNA
      specimens of head and neck SCC prospectively collected in PreservCyt as well as
      on archival slides with either Pap or DQ stain.

PMID- 22378085
TI  - Cytologic diagnosis of intravascular papillary endothelial hyperplasia: a report
      of two cases and review of cytologic literature.
AB  - BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH), previously
      known as 'Masson's hemangioma', is a reactive endothelial proliferation that
      occurs most commonly in the vessels of the head, neck, and extremities. The
      cytologic findings of the lesion are varied and depend on the age of the lesion.
      CASES: Case 1 is a 61-year-old man who presented with a swelling on the medial
      aspect of the forearm. The clinical diagnosis was lipoma. Cytologic smears showed
      spindle cells tagging onto a rich capillary network and smaller round cells
      arranged around hyaline cores. The cytologic diagnosis was benign vascular tumor.
      On histolopathogic examination a diagnosis of IPEH was given. Case 2 is a 45-year
      old man who presented with swelling on the dorsal aspect of the wrist. The
      cytologic diagnosis of giant cell tumor was made based on the presence of
      scattered spindled cells and multinucleate giant cells. The giant cells had
      various shapes like round or crescent and had 10-25 nuclei. The lesion was
      excised and a diagnosis of IPEH was rendered. CONCLUSION: These two cases
      highlight the varied cytomorphology of IPEH making the pinpoint diagnosis of this
      lesion difficult on cytologic smears.

PMID- 22378086
TI  - Blastic plasmacytoid dendritic cell neoplasm: cytopathologic findings.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive
      hematopoietic neoplasm, which in the past was also known variously as blastic NK
      cell lymphoma, agranular CD4+ natural killer cell leukemia, and CD4+/CD56+
      hematodermic neoplasm. BPDCN is now believed to arise from plasmacytoid dendritic
      cells, but its exact etiology is still unknown. We report here on the
      cerebrospinal fluid (CSF) cytology of a BPDCN, a hypercellular specimen comprised
      of malignant, singly dispersed cells with scant to moderate amounts of pale blue,
      agranular cytoplasm, and uniform round to oval nuclei, fine chromatin, prominent
      nucleoli, occasional cytoplasmic microvacuoles, and pseudopodia. Neither mitoses
      nor karyorrhexis were identified. Flow cytometry of the CSF demonstrated that the
      malignant cells expressed bright CD45, HLA-DR and CD33, dim CD4, heterogeneous
      CD56, and partial CD123. The importance of clinical, histopathological, and
      phenotypic correlation is emphasized. Clinical and histopathological correlation
      and a literature review are also presented. The poor clinical outcome makes it
      important to accurately report this rare tumor in a CSF specimen.

PMID- 22378087
TI  - Metastatic squamous cell carcinoma in cerebrospinal fluid: why a rare diagnosis
      on cytology?
AB  - BACKGROUND: Squamous cell carcinoma metastatic to cerebrospinal fluid (CSF) is a
      rare diagnosis on cytology, and thereby more challenging in comparison to an
      adenocarcinoma metastatic to CSF. We recently encountered a case of metastatic
      squamous cell carcinoma in CSF. The primary site was unknown. A review of the
      literature was performed to understand why this is a rare diagnosis in cytology.
      CASE: A 56-year-old male was diagnosed with a keratinizing squamous cell
      carcinoma involving multiple lymph nodes in the neck. On extensive clinical and
      radiologic evaluation, a primary could not be identified. Subsequently, the
      patient presented with sudden loss of vision (in the right eye), nausea and
      vomiting. MRIs of the lumbar spine and optic nerve were suggestive of
      leptomeningeal and perineural seeding, respectively. Cytologic evaluation of CSF
      revealed a few atypical, round hyperchromatic cells which were confirmed as
      epithelial cells through immunocytochemistry for a broad-spectrum keratin. The
      diagnosis of metastatic carcinoma consistent with squamous cell carcinoma was
      rendered. CONCLUSION: Definitive diagnosis of metastatic squamous cell carcinoma
      is challenging unless clinical evidence is present. Besides other factors, the
      mode of spread to CSF may be responsible for this less common diagnosis.

PMID- 22378088
TI  - Multicentric extranodal Rosai Dorfman disease--a cytological diagnosis, with
      histological corroboration.
AB  - BACKGROUND: Rosai Dorfman disease (RDD) typically presents with massive bilateral
      cervical lymphadenopathy, a viral-like prodrome, elevated erythrocyte
      sedimentation rate, and polyclonal hypergammaglobulinemia. Other lymph nodes may
      be less commonly involved. Extranodal RDD is quite rare, and orbital disease
      accounts for only 10% of the extranodal sites of involvement. Multicentric
      disease has also been described, which is usually accompanied by lymphadenopathy
      either initially or later in the disease course. CASE: We report an extremely
      rare extranodal multicentric disease in a diabetic patient, presenting with
      bilateral orbital involvement, causing ocular motility restriction, which was
      diagnosed on aspiration cytology of the orbital mass. This was followed in quick
      succession by new mass lesions in the lower back and infratemporal fossa. On
      extensive work-up, no lymphadenopathy was detected. The patient responded well to
      surgical debulking of the orbital lesions and systemic steroids. CONCLUSION: Fine
      needle aspiration cytology can be effectively applied for early diagnosis of
      multicentric extranodal RDD. Surgical debulking in such cases may be supplemented
      by systemic steroids.

PMID- 22378089
TI  - Fine needle aspiration in suspected inflammatory breast cancer: case series with
      emphasis on approach to specimen adequacy--are the conclusions justified?

PMID- 22378090
TI  - Amiodarone-induced thyroid dysfunction in an iodine-replete area: epidemiological
      and clinical data.
AB  - INTRODUCTION: The present study aims to evaluate the incidence, types, timing and
      risk factors in amiodarone (AMD)-induced thyroid dysfunction. MATERIAL AND
      METHODS: The study comprised 229 patients from an iodine-replete area (115 women,
      114 men, mean age 63.8 +/- 9.2 years), chronically treated with AMD. The cases
      were clinically investigated prior to, and during treatment, by thyroid 2D and
      color Doppler flow sonography, thyroid function tests (TSH, FT3, FT4), and
      antithyroid antibodies. RESULTS: Of 88 patients (38.4%) who developed thyroid
      dysfunction, 47 (20.5%) presented AMD-induced thyrotoxicosis (AIT) and 41 (17.9%)
      AMD-induced hypothyroidism (AIH). There is an evident prevalence of subclinical
      AIH (29 cases), compared to subclinical AIT (three cases). Regarding clinical
      forms, these prevailed in AIT (44 patients) (p < 0.001, Fisher's exact test).
      Thyrotoxic patients were classified in pathogenic types as follows: 11 cases as
      type 1, 15 cases as type 2, and 21 cases as mixed form. The most important risk
      factor for the development of thyroid dysfunction was represented by the
      underlying thyroid pathology. The patients with previous thyroid abnormalities
      (diffuse or nodular goitre and/or positive antithyroid antibodies) developed
      earlier thyroid dysfunction compared to those with an apparently normal thyroid
      gland. The thyroid dysfunction occurrence was heterogeneous (4-84 months).
      Thyrotoxicosis involved especially young ages, while AIH affected later years.The
      daily dose, the duration of the treatment and the cumulative dose of AMD do not
      represent risk factors in thyroid dysfunction development. The determination of
      serum AMD and desethylamiodarone concentrations does not offer benefits in the
      diagnosis and treatment of thyroid dysfunction. CONCLUSIONS: In the present
      study, the incidence of AIH was similar to that reported in iodine-replete areas.
      The incidence of AIT was higher that previously reported, a fact underlining the
      importance of the proper screening and monitoring of patients. Cases with
      previous thyroid morphologic and/or immunologic abnormalities require frequent
      monitoring.

PMID- 22378091
TI  - Correlation between thyroid volume and humoral thyroid autoimmunity after
      radioiodine therapy in Graves' disease.
AB  - BACKGROUND: Graves' disease is an autoimmune disorder with the presence of TSH
      receptor autoantibodies (TRAb). TRAb are produced mainly by lymphocytes
      infiltrating the thyroid gland. The aim of this study was to investigate the
      influence of the reduction of thyroid volume (TV) on TRAb level after radioiodine
      (RAI) administration in a group of patients with Graves' disease. MATERIAL AND
      METHODS: A retrospective chart review of 36 patients with Graves' disease (age
      range 18-67 yrs; Me 46 yrs; mean age +/- SD 43 yrs +/- 13.0 yrs) treated with RAI
      administration (the mean dose of RAI +/- SD was 46.1 mCi +/- 21.7 mCi ) was
      performed. Data concerning TV, TRAb, TSH, and fT4 was collected immediately
      before administration of radioiodine and 18-36 months thereafter. Data was
      collected before the first administration of RAI and 18-36 months after the last
      administration of RAI for patients treated with repeated doses of RAI. RESULTS:
      Before treatment, mean male (n = 4) TV was 27.9 ml +/- 9.6 ml and mean female (n
      = 32) TV was 20.6 ml +/- 12.7 ml. Mean TV was 2.4 ml +/- 1.7 ml(males) and 5.3 ml
      +/- 10.9 ml (females) after therapy. There was an extremely significant
      difference between mean TV before RAI administration and after 18-36 months.
      There was an extremely significant difference between the mean serum level of
      TRAb before and 18-36 months after RAI therapy. No significant correlation
      between percentage reduction of TV and percentage reduction of serum level of
      TRAb was found. CONCLUSIONS: 1. Decrease of thyroid gland volume after
      radioiodine therapy is followed by a significant decrease of the level of TRAb
      after 18-36 months. 2. TRAb concentration is positively correlated with thyroid
      gland volume. 3. Percentage reduction of TRAb is not correlated with percentage
      reduction of thyroid volume.

PMID- 22378092
TI  - Hashimoto's thyroiditis and carbohydrate metabolism disorders in patients
      hospitalised in the Department of Endocrinology and Diabetology of Ludwik
      Rydygier Collegium Medicum in Bydgoszcz between 2001 and 2010.
AB  - INTRODUCTION: Chronic lymphocytic thyroiditis, also known as Hashimoto's
      thyroiditis, is the most frequent type of thyroiditis. An average of 2% of the
      population have the disease. It occurs in all age groups, also in children. The
      main cause of the disease are autoimmune disorders, which results in incresed
      risk of suffering from type 1 diabetes. Fourthermore, during the course of
      Hashimoto's thyroiditis, hypothyroidism may cause carbohydrate metabolism
      disorders. Aim of our study was estimate disturbances of glycaemia in patients
      with recognized Hashimoto's thyroiditis, hospitalized in Endokrinology and
      Diabetology Depatment of Collegium Medicum University of Nicolaus Copernicus in
      Bydgoszcz in years 2001-2010. MATERIAL AND METHODS: We examined 54 patients with
      the diagnosis of Hashimoto thyroiditis based on clinical picture and
      examination(autoantibodies anti-TPO and anti-Tg). RESULTS: In the tested group
      with Hashimoto's thyroiditis, diabetes has been confirmed in 27.8% of the
      patients; impaired fasting glycaemia (IFG) or impaired glucose tolerance (IGT)
      occurred in 16.6%, whereas a normoglycaemia has been confirmed in 55.6% of the
      pacients. An average age of the patients with Hashimoto's thyroiditis and
      diabetes at the same time, was 53 years. The patients in which we confirmed the
      impaired fasting glycaemia or impaired glucose tolerance were on average 49.9
      years old. An average age of the patients without any carbohydrate methabolism
      disorders was on average 43.1 years. CONCLUSIONS: Carbohydrate metabolism
      disorders in the form of type 1 diabetes connected with an autoimmune process, as
      well as type 2 diabetes connected with the increase of the insulin resistance,
      occured in average of half of the patients with Hashimoto's thyroiditis.

PMID- 22378093
TI  - Plasma arginine vasopressin level in hypothyroid women in relation to dietary
      sodium supply.
AB  - INTRODUCTION: A disturbed regulation mechanism of arginine vasopressin secretion
      in response to plasma osmolality and volaemia changes occurs in hypothyroidism.
      The aim of this study was to determine plasma arginine vasopressin concentration
      in hypothyroid women under conditions of a low sodium diet and in an upright
      position. MATERIAL AND METHODS: Twenty-six women with primary hypothyroidism and
      24 healthy women (control group) were investigated. In all the patients, the
      plasma arginine vasopressin and serum sodium and potassium levels, as well as
      plasma osmolality, were measured first under basal conditions, i.e. after three
      days of a normal sodium diet (120 mmol sodium per day) in a horizontal position,
      and next after three days of a low sodium diet (10 mmol Na per day) in an upright
      position. In hypothyroid patients, the investigations were repeated after a
      euthyroid state as a result of L-thyroxine treatment had been attained. RESULTS:
      An increase of vasopressinaemia, measured under basal conditions as well as after
      three days of the low sodium diet, was shown in untreated hypothyroid patients
      compared to the control group. The arginine vasopressin plasma level normalised
      after a euthyroid state had been attained. As a result of the low sodium diet and
      the upright position, a significant increase of arginine vasopressin secretion
      was observed in the control group and hypothyroid women in the euthyroid state.
      No significant increase of this neuropeptide level in untreated patients was
      shown while applying the low sodium diet and upright position. Plasma osmolality
      and natraemia were decreased in the untreated hypothyroid patients. No
      correlation between vasopressinaemia and plasma osmolality was shown. CONCLUSION:
      The plasma arginine vasopressin level is increased in hypothyroid women, and does
      not change in the upright position under the influence of a low sodium diet.

PMID- 22378094
TI  - The usefulness of determining the serum concentrations of vascular endothelial
      growth factor (VEGF) and its soluble receptor type 2 (sVEGF-2) in the
      differential diagnosis of adrenal incidentalomas.
AB  - INTRODUCTION: Angiogenesis plays an important role in tumour growth, progression
      and invasiveness. Vascular endothelial growth factor (VEGF) is a recognised
      angiogenesis-stimulating factor. Soluble VEGF receptors (sVEGFRs) have
      antiangiogenic properties. Recent studies have indicated that serum
      concentrations of these factors show a good correlation with the aggressiveness
      of these tumours in various organs. The aim of this study was to assess the
      usefulness of determining serum concentrations of VEGF and sVEGFR-2 in patients
      with adrenal incidentalomas. MATERIAL AND METHODS: The study included 51
      patients: 38 women aged 53.57 +/- 10.12 years and 13 men aged 54.66 +/- 12.73
      years without a history of cancer but with non-functioning adrenal tumours
      incidentally detected on a CT scan. The analysis of the CT images included such
      morphological features of the tumour as: tumour size, tumour homogenicity, tumour
      density before and after administration of an intravenous contrast medium, and
      the value of percentage washout of the contrast medium from the tumour. Based on
      the above criteria, we identified a group of 40 patients with adrenal tumours who
      met the CT criteria for benign adenomas (Group 1) and 11 patients whose
      incidentally discovered tumours did not meet the radiological criteria for benign
      adenomas, thereby providing grounds for referring these patients for surgery
      (Group 2). The control group consisted of 20 healthy sex- and age-matched
      individuals. RESULTS: The mean serum concentrations of VEGF in the study and
      control groups were similar, although patients with adrenal tumours had
      significantly higher concentrations of sVEGFR-2 than healthy individuals. There
      were no significant differences in the mean concentrations of VEGF and sVEGFR-2
      between the patients undergoing surgery (Group 2) and the patients not undergoing
      surgery (Group 1), or between the patients undergoing surgery (Group 2) and the
      control group. Postoperative histopathology of the resected adrenal tumours
      revealed benign adrenocortical adenoma in eight patients and the following in the
      remaining patients: adrenocortical carcinoma in one patient, phaeochromocytoma in
      one patient and ganglioneuroma in one patient. The adrenocortical carcinoma
      patient had the highest concentration of VEGF, while this patient's concentration
      of sVEGFR-2 was the lowest in the study group. In the patients diagnosed with
      ganglioneuroma and phaeochromocytoma, VEGF and sVEGFR-2 concentrations did not
      differ significantly from their mean concentrations in the study group. There
      were also no relationships between the serum concentrations of VEGF or sVEGFR-2
      and the following parameters: tumour size, precontrast and postcontrast tumour
      densities or the value of percentage washout. Positive correlations were,
      however, identified between the concentration of VEGF and the concentrations of
      total cholesterol and LDL-cholesterol. CONCLUSIONS: Determining the serum
      concentrations of such angiogenesis markers as VEGF and sVEGFR-2 seems useful in
      the evaluation of the nature of incidentally detected adrenal masses
      (incidentalomas), especially in the preoperative differential diagnosis of
      adrenal masses that do not meet the CT criteria for benign tumours.

PMID- 22378095
TI  - Association of body mass index and serum vitamin D level in healthy Iranian
      adolescents.
AB  - INTRODUCTION: In studies of obese adolescents in various countries, vitamin D
      deficiency has been correlated with greater weight and elevated BMI. However,
      there is insufficient data on the relation between vitamin D status and body fat
      indexes in adolescence. The aim of this study was to investigate the association
      of serum (25[OH]D) concentrations with body mass index of healthy Iranian
      subjects to understand whether specific data on the relation between vitamin D
      status and body mass index is common in all populations. MATERIAL AND METHODS:
      Data was collected from 259 ambulant medical staff adults, students and other
      subjects who met the inclusion criteria of the study. Body mass index and fasting
      25-Hydroxy vitamin D level were measured. Vitamin D deficiency was defined as
      having a 25(OH)D concentration < 25 nmol/L. RESULTS: Participants were aged 20-64
      years, mean age 34 +/- 9 years, and about 57.5% of the participants were women.
      The mean (+/- SD) body mass index (kg/m2) was 24.2 +/- 3.8 kg/m2 (median = 23.7
      kg/m2), the mean (+/- SD) vitamin D level of the participants was 29 +/- 16
      nmol/L (median = 26 nmol/L), and 48% of the participants had vitamin D
      deficiency. In this study, there was no significant association between vitamin D
      level and BMI (r = 0.064; p = 0.307) (age adjusted). Moreover, there was no
      association between vitamin D level and sex of the participants. In addition, no
      association between BMI and sex of the adolescents was seen (p; NS), but a
      significant association between age and vitamin D level was found (r = 0.002).
      CONCLUSION: Our data suggests that various mechanisms could potentially
      contribute to the robust association of vitamin D with adiposity; in normal or
      near normal BMI, vitamin D status may not be correlated with age.

PMID- 22378096
TI  - Analysis of the impact of environmental and social factors, with a particular
      emphasis on education, on the level of metabolic control in type 1 diabetes in
      children.
AB  - BACKGROUND: Type 1 diabetes is a chronic, incurable childhood disease.
      Chronically uncontrolled diabetes is associated with eye, kidney, nerve, heart
      and blood vessel damage and function impairment. The aim of this study was to
      evaluate the impact of various social and environmental factors, with a
      particular emphasis on education, on the level of metabolic control in diabetes.
      MATERIAL AND METHODS: The survey research was conducted in 102 children aged 0-18
      years, diagnosed with type 1 diabetes. Based on the HbA(1c ) level, patients were
      divided into: group A (63 patients with fairly well and moderately controlled
      type 1 diabetes mellitus) and group B (39 patients with metabolically
      uncontrolled type 1 diabetes mellitus). The impact of various environmental and
      social factors on the degree of metabolic control of type 1 diabetes was
      analysed. RESULTS: No effect of typical environmental and social factors, such
      as: place of residence, gender, parents' education and their professional
      activity, on the level of metabolic control of type 1 diabetes was found.
      However, groups A and B significantly differed in the level of knowledge about
      diabetes and its treatment, in the regularity of meals, in possessing a nutrition
      scale and in the self-assessed preparation for taking care and custody of a child
      with type 1 diabetes. CONCLUSIONS: 1. Children with type 1 diabetes and their
      parents require ongoing education about the disease and its treatment. 2. The
      regularity of meals and the use of a nutrition scale have considerable impact on
      the level of metabolic control of the disease.

PMID- 22378097
TI  - Psychological stress and the function of male gonads.
AB  - Stress is generally a natural phenomenon that affects behaviour, physiological
      processes, and neuroendocrine, neurochemical, neurological and immune responses.
      Many somatic and mental disorders are thought to result from chronic stress.
      Stress-induced gonadal dysfunction  is not restricted to humans, but is observed
      in all higher animals. Stress-induced gonadal dysfunction comprises disturbances
      of the hypothalamic-pituitary-gonadal axis and of spermatogenesis. Various
      stressors induce changes in the secretion of neurotransmitters and hormones, such
      as CRH, ADH, beta-endorphins, somatostatin, VIP, PRL, GH, TSH, dopamine,
      serotonin, neuropeptide Y, melatonin, ACTH, glucocorticosteroids, catecholamines
      and androgens. In acute stress, testicular function is principally modified by
      cytokines and fluctuating concentrations of gonadotropins, while in chronic
      stress, hypogonadotropic hypogonadism and disruption of spermatogenesis of
      varying  severity, including spermatogenetic arrest, are observed. In spite of
      the decades-long interest in the relationships between psychological  stress and
      the function of male gonads, many questions in this area remain unanswered.

PMID- 22378098
TI  - Agranulocytosis during treatment of chronic hepatitis C complicated by
      hyperthyreosis. Case reports.
AB  - Agranulocytosis is a life-threatening disorder characterised by a greatly
      decreased number of circulating neutrophils below 500/MUL. This  article presents
      two cases of agranulocytosis in patients treated with pegylated interferon and
      ribavirin due to chronic hepatitis C. Interferon  induced hyperthyroidism, which
      required the use of a tyreostatic. Anti-thyroid drugs (ATD) used to treat
      hyperthyroidism can cause agranulocytosis. The synergistic reaction of ATD and
      interferon on bone marrow cannot be excluded.

PMID- 22378099
TI  - Parathyroid adenoma with coeliac disease: primary or quaternary
      hyperparathyroidism?
AB  - Coeliac disease is a gluten-sensitive enteropathy of varying severity.
      Osteomalacia and hypocalcaemia can result from malabsorption of  vitamin D and
      calcium, which, in turn, can lead to secondary hyperparathyroidism. If coeliac
      disease remains untreated for long, tertiary  hyperparathyroidism can also
      develop through autonomy of the parathyroid glands via chronic stimulation.
      Primary hyperparathyroidism also has been reported in some cases of coeliac
      disease. We report the case of an adolescent with coeliac disease presenting with
      severe hypercalcaemia from a parathyroid adenoma. A 14 year-old girl was admitted
      to our department for delayed puberty and growth retardation. Laboratory
      examination revealed iron deficiency anaemia, low 25OH vitamin D level (7 ng/ml),
      high parathyroid hormone level (PTH) (955 pg/ml), and hypercalcaemia (13.4
      mg/dl). Endoscopic biopsy was compatible with gluten enteropathy. Endomysium
      antibody was positive. A gluten-free diet was started. Her calcium returned to
      normal after excision of the parathyroid adenoma. After four months of the gluten
      free diet, she began to mature, and puberty began with development of breasts and
      axillary-pubic hair growth. It has been  suggested that autonomous four-gland
      hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation,
      and that this  should be termed "quaternary hyperparathyroidism". More studies
      are required to explain the relationship between coeliac disease and
      hyperparathyroidism.

PMID- 22378100
TI  - A non-functioning pancreatic neuroendocrine tumour: a case report.
AB  - We present the diagnostic and therapeutic difficulties encountered in a patient
      with a clinically advanced pancreatic neuroendocrine tumour. The report concerns
      a 60-year-old female patient with the diagnosis of non-functioning pancreatic
      neuroendocrine tumour (NET G1) with liver, peripancreatic lymph node and
      mediastinal metastases. Due to the presence of advanced disease (inoperable
      pancreatic tumour, presence of multiple metastases) the patient was considered
      ineligible for surgical treatment on two occasions. Tissue samples for
      histopathology were collected during an exploratory laparotomy, which made it
      possible to establish the diagnosis. As somatostatin  receptor scintigraphy was
      positive, the patient was started on somatostatin analogues and radionuclide
      therapy was initiated, resulting in satisfactory response in the form of complete
      remission of liver metastases and the decreased size of the primary tumour in the
      pancreas. The use of somatostatin analogues in the case of an inoperable
      neuroendocrine tumour which was assessed as clinically advanced, yet  possessing
      a low proliferative potential, is a promising therapeutic option.

PMID- 22378101
TI  - Interferon-induced thyroiditis during treatment  of chronic hepatitis C.
AB  - Thyroid function disorders affect between 5% and 15% of patients treated with
      IFNalpha and RBV for chronic hepatitis C. Women and patients with thyroid
      peroxidase antibodies (TPOAb) found before the treatment are at risk of
      developing the disorders (46.1% vs. 5.4%). The spectrum of IFNalpha-induced
      thyroiditis (IIT) includes two groups. Disorders with an autoimmune background
      are: presence of thyroid autoantibodies without clinical disease, Hashimoto's
      disease and Graves' disease. The second group comprises diseases caused by the 
      direct toxic effect of IFNalpha on the thyroid gland, i.e. destructive
      thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are  not an
      absolute contraindication for IFNalpha and RBV therapy. In patients diagnosed
      with thyroid dysfunction, before the antiviral therapy it is necessary to achieve
      euthyreosis. Thyroid function disorders may occur at any moment of the therapy.
      The earliest have been observed in the 4th week of treatment, and the latest 12
      months after its termination. During the therapy, in order to diagnose IIT early,
      it is recommended to determine TSH level every 2-3 months depending on the
      presence of TPOAb before the treatment. The diagnosis and treatment of thyroid
      function disorders should be conducted in co-operation with an endocrinologist.

PMID- 22378102
TI  - Adrenal imaging.
AB  - The differentiation of adrenal nodules is wide and varies from primary benign
      neoplasia, through hormone secreting lesions, to primary and secondary malignant
      masses. With the rapid development of cross-sectional imaging, incidental
      detection of adrenal nodules has become an everyday practice, leaving clinicians
      with the necessity of further investigation. In this article, we present the
      current possibilities of adrenal gland imaging and we propose a diagnostic schema
      for differential diagnosis of incidentaloma. Non-contrast enhanced  computer
      tomography (CT) is a modality of choice used for the differential diagnosis of
      adrenal lesions. It allows the detection of 95% of adrenal masses, and the
      characterisation of most of them. Magnetic resonance imaging (MRI) is a good
      modality for cases in which CT  examination cannot determine the character of an
      adrenal tumour. Nuclear medicine study with the use of Iodine-131 meta
      iodobenzylguanidine(MIBG) is helpful in the diagnosis of pheochromocytoma.
      Positron Emission Tomography-Computed Tomography (PET-CT)  is considered a useful
      method in patients with a known malignancy history. Ultrasound has a low
      sensitivity for the detection of small  lesions and is not capable of reliable
      characterisation of visualised masses. However, this technique plays an important
      role in the follow-up  of non-hypersecreting adrenal lesions.

PMID- 22378103
TI  - [Dear Colleagues and Readers].

PMID- 22378104
TI  - Fixed drug eruption induced by cyclophosphamide.

PMID- 22378105
TI  - Acute obstructive hydrocephalus due to a large posterior third ventricle choroid
      plexus cyst.
AB  - We present the case of a child in whom acute hydrocephalus developed secondary to
      obstruction of the foramen of Monro by a choroid plexus cyst. The patient was
      seen in the emergency department with fevers, acute onset of headaches, and
      lethargy. Computed tomography demonstrated dilated lateral and third ventricles
      with a relatively normal-sized fourth ventricle. An external ventricular drain
      was placed. Despite decompression of the lateral ventricles, follow-up magnetic
      resonance imaging demonstrated a dilated third ventricle with a possible thin
      walled mass extending from the foramen of Monro into the posterior portion of the
      third ventricle. The patient subsequently underwent endoscopic fenestration of
      the cyst with endoscopic third ventriculostomy. Although two other cases of
      symptomatic choroid plexus cysts of the third ventricle have been previously
      reported in children, our paper highlights the possibility of endoscopic cyst
      fenestration together with a third ventriculostomy as a treatment option in cases
      where the cyst extends into the posterior third ventricle. Despite adequate
      decompression, we were concerned that due to CSF pulsations the remnant cyst wall
      could result in acute aqueduct obstruction and subsequent hydrocephalus.

PMID- 22378106
TI  - Cutaneous innervation and itch in keloids.

PMID- 22378107
TI  - Topical calcineurin inhibitors in the treatment of steroid-dependent atopic
      keratoconjunctivitis.
AB  - PURPOSE: To evaluate the long-term effectiveness of the combination of topical
      cyclosporine drops and tacrolimus ointment in the treatment of steroid-dependent
      atopic keratoconjunctivitis (AKC). METHODS: Ten patients with moderate to severe
      AKC participated in the study. Topical cyclosporine 0.05% was used, as a
      monotherapy, 6 times daily during the first month of the study, followed by 4
      times daily during the second month. The patients were then instructed to self
      treat with topical cyclosporine at a dose ranging from 2 to 6 times daily
      depending on the severity of the disease. Tacrolimus ointment 0.03% was applied
      on the lid skin. Follow-up examinations were performed approximately every 3
      months. Each patient completed a follow-up period of at least 12 months. Symptoms
      and signs of AKC were assessed on the day of enrollment, on days 28, 56, and 63,
      and at subsequent follow-up visits. Flare-ups of AKC requiring steroid use and
      progression of the disease findings were also recorded. RESULTS: All patients
      experienced significant improvement of their symptoms and signs during the first
      2 months of the study. Two patients were lost to follow-up after the initial 2
      months. One patient was noncompliant and continued the treatment only for 7
      months. During the median treatment period of 21.5 months for the 7 continuing
      patients, a total of only 2 flare-up episodes were noted requiring topical
      steroids. CONCLUSIONS: Adequate topical immunomodulation using topical
      calcineurin inhibitors may eliminate the need for steroids and favorably alter
      the long-term prognosis of patients with AKC.

PMID- 22378108
TI  - Contact lens materials, mucin fragmentation and relation to symptoms.
AB  - PURPOSE: Mucins adhere to contact lenses (CLs), reflecting the renewal of the
      preocular fluid and enzymatic activity at the ocular surface. In this study, we
      aimed to analyze mucin fragmentation on materials new to the ocular surface and
      investigate whether this correlates with wearing comfort. METHODS: Lenses were
      obtained from new CL wearers after 2 weeks each of wearing vifilcon A, followed
      by senofilcon A, and then by vifilcon A lenses. Symptoms were evaluated using the
      Ocular Surface Disease Index (OSDI). CLs were extracted in a mixture of
      guanidinium hydrochloride and radioimmunoprecipitation assay buffer. Mucin
      mobility was analyzed after electrophoresis, Western blotting, and visualization
      with antibodies against mucin peptide core. Mobilities, normalized to total
      reactivity in the lane, were compared between visits for each subject and were
      expressed as shifts. RESULTS: Mucin (MUC)5AC polymers exceeding 260 kDa were
      observed in agarose gels; NuPAGE resolved polymers from 260 to 3.5 kDa: when
      large mucins were detected, the smallest fragments were missing. Fragmentation
      patterns were significantly different between lens types for MUC1 (analysis of
      variance, P = 0.006) and MUC4 (P < 0.001) but not for MUC5AC or MUC16 (P >
      0.293). Mobility shifts of MUC1 and MUC4 were significantly negatively correlated
      (Pearson, r = -0.908; P = 0.002). For OSDI scores >15, mucin fragmentation was
      unchanged, whereas for OSDI scores <15, MUC4 and MUC5AC fragments were longer on
      vifilcon A than on senofilcon lenses (unpaired t test, P = 0.046), irrespective
      of the direction of change (analysis of variance, P > 0.366). Changes in MUC1
      breakdown were significantly negatively correlated to the overall OSDI score (r =
      -0.891, P = 0.001). CONCLUSIONS: In asymptomatic CL wearers, only changes in
      mucin fragmentation in response to a new material were consistent and fast,
      irrespective of CL order. Lack of change seems, therefore, to be connected with
      discomfort during CL wear.

PMID- 22378109
TI  - Distribution of aqueous-deficient and evaporative dry eye in a clinic-based
      patient cohort:  a retrospective study.
AB  - PURPOSE: To evaluate in a general clinic-based cohort of patients with dry eye
      disease (DED) the distribution of patients with aqueous-deficient or evaporative
      subtype of DED. METHODS: Schirmer tests and meibomian gland dysfunction (MGD)
      (Foulks-Bron scoring) were evaluated in both eyes of 299 normal subjects and DED
      patients (218 women and 81 men) across 10 sites in the European Union and the
      United States. Using the more severe measurement of the 2 eyes, subjects were
      considered to have pure aqueous-deficient dry eye (ADDE) with Schirmer values of
      <7 mm and MGD grades of <=5. Patients were classified as purely evaporative dry
      eye with MGD grades of >5 and Schirmer values of >=7 mm. Subjects were placed
      into the mixed (hybrid) category if they exhibited both a low Schirmer value of
      <7 and evidence of MGD with a grade >5. RESULTS: Of the 224 subjects classified
      with DED using an objective, composite, disease severity scale, 159 were
      classified into 1 of 3 categories: 79 were classified with only MGD, whereas only
      23 were classified as purely aqueous deficient, and 57 showed evidence of both
      MGD and aqueous deficiency. Overall, 86% of these qualified DED patients
      demonstrated signs of MGD. The remaining 65 patients showed evidence of DED
      through other clinical signs, without overt evidence of MGD or ADDE, possibly
      because of the inherent variability of these signs. CONCLUSIONS: The proportion
      of subjects exhibiting signs of evaporative dry eye resulting from MGD far
      outweighs that of subjects with pure ADDE in a general clinic-based patient
      cohort.

PMID- 22378110
TI  - Descemet stripping automated endothelial keratoplasty for spontaneous descemet
      membrane detachment in a patient with osteogenesis imperfecta.
AB  - PURPOSE: To report the first use of Descemet stripping automated endothelial
      keratoplasty (DSAEK) for spontaneous Descemet membrane detachment in a patient
      with osteogenesis imperfecta (OI), keratoconus, and acute bullous keratopathy.
      METHODS: A case report of a 25-year-old man with OI and symptomatic unilateral
      bullous keratopathy secondary to spontaneous Descemet membrane detachment is
      described. The patient presented with acute loss of vision in his right eye and
      was noted on slit-lamp examination to have a totally detached and taut Descemet
      membrane, spanning the anterior chamber. This diagnosis was confirmed with an
      anterior segment OCT (Visante; Carl Zeiss Meditec, Dublin, CA). RESULTS: After an
      attempt to reattach the Descemet membrane with air bubbling was unsuccessful, the
      patient underwent successful DSAEK. Seven months postoperatively, his best
      spectacle-corrected visual acuity was 20/50 compared with his other eye, which
      was 20/40. There were some central folds in the donor noted immediately
      postoperatively that have persisted. CONCLUSIONS: To the best of our knowledge,
      this case is the first documented spontaneous Descemet membrane detachment in a
      patient with OI and probable keratoconus treated successfully with DSAEK. Unlike
      in classical keratoconus hydrops, medical management is unlikely to resolve a
      total Descemet membrane detachment. This unusual Descemet membrane detachment was
      tightly stretched across the anterior chamber without any obvious tear, making
      simple air or gas bubble apposition impossible. Attempts to tear the Descemet
      membrane and then bubble led to significant folds. DSAEK was successful in
      removing the detached Descemet membrane and replacing it with the donor tissue.

PMID- 22378111
TI  - Correlation between optical coherence tomography-derived assessments of lower
      tear meniscus parameters and clinical features of dry eye disease.
AB  - PURPOSE: To measure the correlation between subjective symptom score,
      conventional clinical tests, and Fourier-domain optical coherence tomography (FD
      OCT) of lower tear meniscus parameters in patients with dry eye disease. METHODS:
      Eighteen patients with dry eye disease requiring medical therapy and/or punctal
      occlusion were recruited for this prospective, nonrandomized, observational case
      series. Severity of symptoms of dry eye disease was assessed using the Indiana
      University Dry Eye Questionnaire 2002. Clinical assessments were completed using
      slit-lamp biomicroscopy, rose bengal dye staining, fluorescein tear breakup time
      (TBUT), and a 5-minute Schirmer test with topical anesthesia. The lower tear
      meniscus was imaged using an FD-OCT system with 5-MUm axial resolution and
      measured manually by a masked grader using computer calipers. Correlation was
      assessed using Spearman correlation coefficient (rho). RESULTS: The mean (+/-SD)
      scaled symptom score was 58 +/- 21, with a range of 0 to 100. Vital staining test
      averaged 1.7 +/- 3.4, TBUT averaged 4.4 +/- 1.8 seconds, and Schirmer tests
      averaged 10.2 +/- 8.1 mm. As determined by optical coherence tomography, the
      meniscus height was 228 +/- 153 MUm, depth was 127 +/- 79 MUm, and cross
      sectional area was 0.018 +/- 0.021 mm. Optical coherence tomography meniscus area
      was negatively correlated with the symptom questionnaire score (P < 0.01) and
      positively correlated with Schirmer test results (P < 0.01). There was no
      significant correlation between symptom score and rose bengal staining, TBUT, or
      Schirmer test results (P > 0.01). CONCLUSIONS: Lower tear meniscus measurement
      with FD-OCT is an objective noninvasive test that correlates well with symptoms
      of dry eye disease and the Schirmer test.

PMID- 22378112
TI  - Clinical and corneal biomechanical changes after collagen cross-linking with
      riboflavin and UV irradiation in patients with progressive keratoconus: results
      after 2 years of follow-up.
AB  - PURPOSE: To assess the biomechanical and keratometric effects and the safety of
      treatment of progressive keratoconus with UV-riboflavin collagen cross-linking
      (CXL). METHODS: This is a prospective clinical controlled study. Fourteen eyes of
      14 patients with progressive keratoconus were treated with CXL after corneal
      deepithelization. Patients were assessed preoperatively, at week 1 and at months
      1, 3, 6, 9, 12, and 24 after treatment. We measured uncorrected visual acuity
      (UCVA) and best spectacle-corrected visual acuity (BSCVA) (logarithm of the
      minimum angle of resolution), refraction, biomicroscopy and fundus examination,
      intraocular pressure, axial length, endothelial cell density, corneal topography,
      minimal corneal thickness, macular optical coherence tomography, and corneal
      biomechanics with the ocular response analyzer. RESULTS: Comparing the
      preoperative results with 24-month postoperative results, we observed significant
      improvement in BCVA (0.21 +/- 0.1 to 0.14 +/- 0.1, P = 0.002) and stability in
      UCVA (0.62 +/- 0.5 and 0.81 +/- 0.49, P = 0.475). We observed a significant
      decrease in steepest-meridian keratometry (diopters) (53.9 +/- 5.9 to 51.5 +/-
      5.4, P = 0.001) and in mean cylinder (diopters) (10.2 +/- 4.1 to 8.1 +/- 3.4, P =
      0.001). Significant elongation of the eyes was observed, from 24.39 +/- 1.7 mm to
      24.71 +/- 1.9 mm (P = 0.007). No significant change was observed in mean
      simulated keratometry, minimal corneal thickness, endothelial cell density,
      corneal hysteresis, and corneal resistance factor or foveal thickness.
      CONCLUSIONS: Two years after CXL, the observation of stable UCVA, improved BCVA,
      and reduced keratometry suggests stabilization in progression of keratoconus.
      Unchanged corneal thickness, endothelial cell density, and foveal thickness
      suggest the long-term safety of this procedure. The observed increase in axial
      length and stability in corneal biomechanical parameters measured with the ocular
      response analyzer require further study for verification and explanation.

PMID- 22378113
TI  - The safety and efficacy of linezolid and daptomycin as an additive in Optisol-GS
      against methicillin-resistant Staphylococcus aureus.
AB  - PURPOSE: To evaluate the efficacy of adding either linezolid or daptomycin to
      Optisol-GS donor storage medium in reducing methicillin-resistant Staphylococcus
      aureus (MRSA) contamination of donor corneas. METHODS: Optisol-GS was
      supplemented with either linezolid at 2*, 4*, or 10* minimum inhibitory
      concentration (MIC) or daptomycin and calcium at 5* or 50* MIC. Unsupplemented
      control groups were also used. Gentamicin-sensitive and gentamicin-resistant
      isolates of MRSA were added, and vials were refrigerated for 48 hours followed by
      sampling for viable colony counts immediately upon removal from refrigeration and
      after warming to room temperature for 3 hours. Safety studies of Optisol-GS
      supplemented with 50* MIC daptomycin and calcium were performed by evaluating the
      central corneal thickness and endothelial cell density of the donor cornea.
      Stability of daptomycin in Optisol-GS at storage was also tested. RESULTS: No
      added benefit was observed with linezolid supplementation to Optisol-GS against
      gentamicin-sensitive MRSA, with reduction in viable colony counts by >90% in all
      groups. No benefit was observed with linezolid supplementation against gentamicin
      resistant MRSA, with the majority of inocula remaining viable in all groups.
      Viable counts of gentamicin-sensitive MRSA and gentamicin-resistant MRSA were
      effectively reduced with both 5* MIC and 50* MIC daptomycin supplementation. 50*
      MIC daptomycin-supplemented Optisol-GS had no appreciable effect on the central
      corneal thickness or endothelial cell density of the donor cornea and was stable
      at storage for 14 days. CONCLUSIONS: The addition of daptomycin to Optisol-GS
      significantly increases the anti-MRSA activity of the medium without any apparent
      negative effects on donor corneal tissue.

PMID- 22378114
TI  - Dual laser-assisted lamellar anterior keratoplasty with top hat graft:  a
      laboratory study.
AB  - OBJECTIVES: To develop a dual laser-assisted lamellar anterior keratoplasty
      (LALAK) technique, using excimer and femtosecond lasers to perform surgery on eye
      bank eyes. METHODS: First, we compared corneal stromal surfaces produced by (1)
      deep excimer ablation, (2) femtosecond lamellar cuts, and (3) manual dissection
      and evaluated the effect of excimer laser smoothing with fluid masking on each
      surface. Masked observers graded scanning electron microscopy images on a 5-point
      roughness scale. Then, we performed a 6-mm diameter excimer laser
      phototherapeutic keratectomy ablation to a residual bed thickness of 200 MUm,
      followed by laser smoothing. We used the femtosecond laser to cut donors in a
      modified top hat design with a thin tapered brim, which fitted into a manually
      dissected circumferential pocket at the base of the recipient bed. Fourier domain
      optical coherence tomography was used to measure corneal pachymetry and evaluate
      graft fit. RESULTS: Deep excimer ablation with smoothing (n = 4) produced a
      significantly (P < 0.05) smoother surface (grade = 3.5) than deep excimer alone
      (n = 4, grade = 3.8) or manual dissection with (n = 1, grade = 3.8) and without
      smoothing (n = 1, grade = 4.8). Deep femtosecond cuts (n = 2) produced
      macroscopic concentric ridges on the stromal surface. Experimental LALAK was
      performed on 4 recipients prepared by deep excimer ablation and 4 donors cut with
      the femtosecond laser. After suturing, good peripheral graft-host match was
      observed on Fourier domain optical coherence tomography imaging. CONCLUSION:
      These preliminary studies show that the LALAK technique permits improved
      interface smoothness and graft edge matching. Clinical trials are needed to
      determine whether these improvements can translate to better vision.

PMID- 22378115
TI  - Peripheral sterile corneal ring infiltrate after riboflavin-UVA collagen cross
      linking in keratoconus.
AB  - PURPOSE: To present 7 cases of peripheral sterile corneal infiltrates that
      occurred after corneal cross-linking (CXL) for progressive keratectasia. METHODS:
      Seven patients who had their progressive keratoconus documented underwent corneal
      deepithelization and subsequently CXL, which was performed with the application
      of 0.1% riboflavin with 20% dextran, and exposure to UVA light (370 nm, 2.9-3.1
      mW/cm(2)) for 30 minutes. RESULTS: Nearly a week after the procedure, the
      patients presented with peripheral stromal infiltrates. The ring-like infiltrates
      were superficial and were present at the 9.0-mm zone. Sterile infiltration was
      diagnosed. Patients were treated with topical corticosteroids, and complete
      resolution was achieved after a few weeks of treatment. CONCLUSIONS: We
      hypothesize that the phototoxic effect on the corneal stroma may be the main
      mechanism that triggers these infiltrates. Alternatively, alterations in
      antigenicity that occur in native proteins after CXL could result in patients
      recognizing the proteins as nonself and mounting immune responses.

PMID- 22378116
TI  - Bilateral herpes simplex keratitis presenting as peripheral ulcerative keratitis.
AB  - PURPOSE: To report a case of bilateral Herpes simplex keratitis (HSK)
      masquerading as peripheral ulcerative keratitis (PUK). METHODS: A case of a 47
      year-old female complaining of painful red eyes with a history of arthritis and
      anterior uveitis attacks with positive antinuclear antibodies (ANA).
      Biomicroscopy revealed PUK, stromal infiltrations and bilateral central corneal
      epithelial erosions. Slit-lamp examination disclosed +3 anterior chamber cells in
      both eyes. RESULTS: Blood testing was positive for ANA. Herpes simplex virus
      (HSV) antigen was identified in both eyes using polymerase chain reaction (PCR).
      The management included topical prednisolone and acyclovir, as well as systemic
      valacyclovir. Improvement of epithelial corneal defects, PUK, and visual acuity
      was achieved gradually during the follow-up period. CONCLUSIONS: Bilateral
      herpetic keratitis presenting as PUK is an extremely rare manifestation of
      herpetic disease. PUK can pose a diagnostic dilemma in cases with immune system
      dysregulation. Excluding infectious agents is mandatory for appropriate
      treatment.

PMID- 22378117
TI  - Colored cosmetic contact lenses:  an unsafe trend in the younger generation.
AB  - PURPOSE: To identify the microbiological profile and evaluate the clinical course
      and outcomes in patients who developed severe infectious keratitis after colored
      cosmetic contact lens wear. METHODS: This case series includes 13 patients who
      developed severe infectious keratitis after colored cosmetic contact lens wear. A
      detailed history regarding contact lens availability and storage and handling
      techniques was taken. All patients underwent standard diagnostic microbiological
      evaluation followed by culture-guided topical antimicrobial therapy. RESULTS: Of
      13 patients, 8 were male and 5 were female, with mean age at presentation of 19
      +/- 3.8 years. All patients were emmetropic, and lenses were worn solely for
      cosmetic purposes. Seven lenses were dispensed without prescription or fitting
      from an unlicensed optical shop, 5 patients had shared lenses with
      friends/relatives, and 1 patient obtained the lens from the garbage. None of the
      patients followed the recommended contact lens handling and storage techniques.
      The causative microorganisms included Pseudomonas aeruginosa (54%),
      Staphylococcus aureus (25%), and Staphylococcus epidermidis (17%), with 1 case of
      viral keratitis. In 62% of cases, ulcer size was >=5 * 5 mm and posttreatment
      corrected visual acuity was 6/24 or less. All patients responded well to topical
      antimicrobials, and none required surgical intervention. CONCLUSIONS: Over-the
      counter use of decorative lenses as a cosmetic aid is rapidly increasing. Easy
      and unmonitored availability of these cosmetic lenses is followed by severe sight
      threatening complications in young emmetropic individuals.

PMID- 22378118
TI  - Lenses on biology.

PMID- 22378119
TI  - Q&A: Circuit capacity. Interview by Richard Saltus.

PMID- 22378120
TI  - Climate Change: A planet in flux.

PMID- 22378121
TI  - Q&A: Regime change. Interview by Hannah Hoag.

PMID- 22378122
TI  - Ocean Science: The power of plankton.

PMID- 22378123
TI  - Cancer: Solving an age-old problem.

PMID- 22378124
TI  - Q&A: A slow-motion crisis. Interview by Michael Eisenstein.

PMID- 22378125
TI  - Stem Cells: Flexible friends.

PMID- 22378126
TI  - Q&A: Stemming the tide of misinformation. Interview by Michael Eisenstein.

PMID- 22378127
TI  - Q&A: Controversy and intellect. Interview by Julie Corliss.

PMID- 22378128
TI  - Synthetic Biology: Bits and pieces come to life.

PMID- 22378129
TI  - The participation of community members on medical institutional review boards.
AB  - The goal of this study was to describe the contributions of community members
      (unaffiliated members) who serve on institutional review boards (IRBs) at large
      medical research centers and to compare their contributions to those of other IRB
      members. We observed and audiotaped 17 panel meetings attended by community
      members and interviewed 15 community members, as well as 152 other members and
      staff. The authors coded transcripts of the panel meetings and reviewed the
      interviews of the community members. Community members played a lesser role as
      designated reviewers than other members. They were infrequently primary reviewers
      and expressed hesitation about the role. As secondary or tertiary reviewers, they
      were less active participants than other members in those roles. Community
      members were more likely to focus on issues related to confidentiality when
      reviewing an application than other reviewers. When they were not designated
      reviewers, however, they played a markedly greater role and their discussion
      focused more on consent disclosures than other reviewers. They did not appear to
      represent the community so much as to provide a nonscientific view of the
      protocol and the consent form.

PMID- 22378130
TI  - Analysis of the status of subject recruitment in clinical trials in Shandong,
      China.
AB  - Although subject recruitment for clinical trials in Shandong has been carried out
      with an awareness of international regulatory and ethical frameworks, there have
      been some defects in the recruitment process. The objective of this study is to
      analyze the current status of subject recruitment in Shandong. We conducted a
      survey among 198 principal investigators (PIs) and 543 subjects. The results were
      summarized and calculated as a percentage according to the responses to each
      question by PIs and subjects. This survey indicated that the ethics committee
      should strengthen the review of subject recruitment and enhance ethics training
      among board members. PIs should seek to improve the recruitment process.

PMID- 22378131
TI  - "Walking along beside the researcher": how Canadian REBs/IRBs are responding to
      the needs of community-based participatory research.
AB  - Research ethics boards and institutional review boards (REBs/IRBs) have been
      criticized for relying on conceptions of research that privilege biomedical,
      clinical, and experimental designs, and for penalizing research that deviates
      from this model. Studies that use a community-based participatory research (CBPR)
      design have been identified as particularly challenging to navigate through
      existing ethics review frameworks. However, the voices of REB/IRB members and
      staff have been largely absent in this debate. The objective of this article is
      to explore the perspectives of members of Canadian university-based REBs/IRBs
      regarding their capacity to review CBPR protocols. We present findings from
      interviews with 24 Canadian REB/IRB members, staff, and other key informants.
      Participants were asked to describe and contrast their experiences reviewing
      studies using CBPR and mainstream approaches. Contrary to the perception that
      REBs/IRBs are inflexible and unresponsive, participants described their attempts
      to dialogue and negotiate with researchers and to provide guidance. Overall,
      these Canadian REBs/IRBs demonstrated a more complex understanding of CBPR than
      is typically characterized in the literature. Finally, we situate our findings
      within literature on relational ethics and explore the possibility of researchers
      and REBs/IRBs working collaboratively to find solutions to unique ethical
      tensions in CBPR.

PMID- 22378132
TI  - Science, politics, and identity in northern research ethics licensing.
AB  - The Nunavut Research Institute (NRI) is the ethics board that licenses all
      research conducted in Nunavut, Canada. The NRI is a gate-keeping institution that
      mediates the interaction of Inuit knowledge systems (presented as experientially
      based and orally communicated) and researchers (perceived as practicing harsh
      rationality communicated through inscription). The NRI works to discipline
      Southern ways of knowing into something more culturally appropriate for the
      Inuit, but at the same time also disciplines Inuit ways of knowing, creating a
      paradox even as the Inuit struggle to protect their cultural identity, which has
      been subject to a history of judgment and cultural appropriation. This article
      identifies three effects of this paradox on the NRI; the NRI takes on, first, a
      rigorousness in licensing; second, an emphasis on maximizing benefits to the
      community; and third, the role of defender of local knowledge.

PMID- 22378133
TI  - Tailoring information provision and consent processes to research contexts: the
      value of rapid assessments.
AB  - Guidance requires that consent processes for research be appropriately tailored
      to their cultural context. This paper discusses the use of rapid assessments to
      identify cultural and ethical issues arising when explaining research in studies
      in The Gambia and Ethiopia. The assessments provided insights into appropriate
      ways of providing information to minimize the risk of stigmatizing vulnerable
      research populations; research participants' views about the most important
      information to provide about research and their understandings of research; and
      perceived constraints upon reaching voluntary decisions about participation.
      These insights demonstrate that rapid assessments are a relatively quick and
      inexpensive intervention that can provide valuable information to assist in the
      tailoring of information provision and consent processes to research context
      while maintaining and enhancing participants' fundamental protections.

PMID- 22378134
TI  - Incidental findings in neuroimaging research: a framework for anticipating the
      next frontier.
AB  - While strategies for handling unusual and possibly clinically significant
      anatomical findings on brain scans of research volunteers have been developed and
      implemented across neuroimaging laboratories worldwide, few concrete steps have
      been taken to consider the next frontier: functional anomalies. Drawing on the
      genetics literature, early work in neuroimaging considered actionability to be a
      driving force for determining if and when findings should be disclosed to
      individuals in whom they are detected, as inherent uncertainty raises potential
      ethical dilemmas of misdiagnosing and mislabelling people as patients. Here we
      consider the possibility of incidental findings in brain function during the
      resting state. Our approach does not anchor the resting state as the sine qua non
      of functional incidental findings, but as a path to thinking about where they may
      emerge in the future and how our professional communities need to think about
      thinking about them. We suggest that considering the issues proactively today,
      within a framework that is maximally flexible and open to modification, is better
      than responding reactively after the fact and with no framework at all. We argue
      that there is a duty to consider possible incidental findings despite the
      ambiguities of data interpretation, while working hard to prevent unnecessary
      alarm.

PMID- 22378136
TI  - The potential influence of Internet-based social networking on the conduct of
      clinical research studies.
AB  - The rapid growth of internet usage has led to an explosion of social networking
      sites for discussion of health issues. This provides a forum for subjects to
      communicate with one another during the course of the studies. Previous studies
      have raised concerns about the quality of health information on social networking
      sites, although none have evaluated content related to ongoing clinical trials.
      We reviewed material posted in virtual communities by self-identified clinical
      trial participants. We identified material posted in online health forums that
      could introduce bias into clinical research studies; we believe that this issue
      warrants further study and discussion. Physicians and others who conduct clinical
      trials should be aware of this issue. Study investigators and research teams
      should also talk to their study subjects about where and how they are obtaining
      information in order to prevent behaviors and correct misinformation that could
      put a subject's safety or the study objectives at risk. Given the rapid increase
      in Internet use for health care, a broader evaluation of both the benefits and
      potential risks of social networking among research participants during the
      course of a clinical trial appears warranted.

PMID- 22378135
TI  - Considerations in the construction of an instrument to assess attitudes regarding
      critical illness gene variation research.
AB  - Clinical studies conducted in intensive care units are associated with logistical
      and ethical challenges. Diseases investigated are precipitous and life
      threatening, care is highly technological, and patients are often incapacitated
      and decision-making is provided by surrogates. These investigations increasingly
      involve collection of genetic data. The manner in which the exigencies of
      critical illness impact attitudes regarding genetic data collection is unstudied.
      Given interest in understanding stakeholder preferences as a foundation for the
      ethical conduct of research, filling this knowledge gap is timely. The conduct of
      opinion research in the critical care arena is novel. This brief report describes
      the development of parallel patient/surrogate decision-maker quantitative survey
      instruments for use in this environment. Future research employing this
      instrument or a variant of it with diverse populations promises to inform
      research practices in critical illness gene variation research.

PMID- 22378139
TI  - Manipulating the nanostructure of organogels generated from molecules with a 3
      dimensional truxene core.
AB  - Two new truxene-based 3-dimensional (3-D) molecules self-assembled in cyclohexane
      to give organogels with vesicular and fibrillar nano-morphologies governed by the
      substitution pattern of the peripheral alkyl amido side-chains grafted onto the
      rigid 3-D core.

PMID- 22378140
TI  - Spectroscopic and adsorptive studies of a thermally robust pyrazolato-based PCP.
AB  - The pyrazolato-based PCP [Ni(8)(MU(4)-OH)(4)(MU(4)-OH(2))(2)(MU(4)-PBP)(6)]
      (NiPBP, H(2)PBP = 4,4'-bis(1H-pyrazol-4-yl)biphenyl), whose 3-D architecture is
      built upon octametallic hydroxo clusters reciprocally connected by organic
      spacers, is a very promising candidate for gas adsorption applications, owing to
      its remarkable thermal stability (up to 400  degrees C in air) and its high void
      volume (70%). As such, NiPBP was selected as a proof-of-concept material to
      demonstrate how an optimized set of solid state techniques can concur to create a
      comprehensive and coherent picture, relating (average and local) structural
      features to adsorptive properties. To this aim, the response of NiPBP toward
      different gases, retrieved by gas adsorption measurements (N(2) at 77 K, in the
      low pressure region; H(2) at 77 K, in the high pressure region), was explained in
      terms of local-level details, as emerged by coupling electronic, X-ray
      (absorption and emission), and variable temperature IR spectroscopy.

PMID- 22378141
TI  - IR TrueFISP with a golden-ratio-based radial readout: fast quantification of T1,
      T2, and proton density.
AB  - A promising approach for the simultaneous quantification of relative proton
      density (M(0)), T(1), and T(2) is the inversion-recovery TrueFISP sequence,
      consisting of an inversion pulse followed by a series of balanced steady-state
      free precession acquisitions. Parameters can then be obtained from a mono
      exponential fit to the series of images. However, a segmented acquisition is
      usually necessary, which increases the total acquisition time considerably. The
      goal of this study is to obtain M(0), T(1), and T(2) maps using a single-shot
      acquisition, with T(1) and T(2) measurements in brain that are consistent with
      the published literature, with a 20-fold speed improvement over the segmented
      approach, and at a clinically relevant spatial resolution. To this end, a single
      shot inversion-recovery TrueFISP sequence was combined with a radial view-sharing
      technique. The parameters M(0), T(1), and T(2) were then obtained on a pixel-wise
      basis from a three fit parameter to the signal evolution. The accuracy of this
      method for quantifying these parameters is demonstrated in vivo. In addition,
      further corrections to the quantification necessary owing to other experimental
      factors, namely magnetization transfer and imperfect slice profiles, were
      developed. Including additional scans necessary for these corrections in the
      measurement protocol, the required scan time is increased from approximately 6 to
      18-28 s per slice.

PMID- 22378142
TI  - Elevated proportion of small, dense low-density lipoprotein particles and lower
      adiponectin blood levels predict early structural valve degeneration of
      bioprostheses.
AB  - OBJECTIVES: Long-term durability of bioprosthetic heart valves (BPs) are limited
      by structural valve degeneration (SVD) leading to stenosis and/or regurgitation.
      In this study, we sought to determine the metabolic markers associated with SVD.
      METHODS: In a cohort of 220 patients with an aortic BP (mean follow-up of 2.5 +/-
      1.2 years), we compared the metabolic and blood lipid profile including the
      levels of adiponectin and the proportion of small, dense low-density lipoprotein
      (LDL) particles (%LDL(<)(255A)) in individuals developing echocardiographic
      evidence of early BP hemodynamic dysfunction with subjects having no features of
      BP dysfunction. RESULTS: Patients developing BP dysfunction (n = 69; 31.3%) had a
      tendency of higher triglyceride levels. Moreover, patients with BP dysfunction
      had an increased proportion of %LDL(<)(255A). In multivariate linear regression
      analysis, after adjustment for age, gender, BP size and hypertension, the
      %LDL(<)(255A) (p = 0.04) was significantly associated with BP dysfunction. In
      addition, patients with an elevated level of %LDL(<)(255A) along with a decreased
      plasma adiponectin level were at a very high risk of developing early BP
      hemodynamic dysfunction (OR = 2.54, p = 0.04). CONCLUSION: BP dysfunction is
      significantly associated with an increased proportion of small, dense LDL.

PMID- 22378143
TI  - Highly enantioselective assembly of functionalized tetrahydroquinolines with
      creation of an all-carbon quaternary center.

PMID- 22378144
TI  - Pranlukast, a cysteinyl leukotriene type 1 receptor antagonist, attenuates the
      progression but not the onset of silica-induced pulmonary fibrosis in mice.
AB  - BACKGROUND: Although cysteinyl leukotrienes (CysLTs) have been implicated in the
      etiology of acute inflammatory diseases, recent studies have suggested that they
      also directly stimulate fibroblasts. However, their precise role in the
      pathogenesis of pulmonary fibrosis is unclear. METHODS: In this study, we
      evaluated the effect of both short- and long-term treatment with pranlukast, a
      CysLT type 1 (CysLT(1)) receptor antagonist, on silica-induced pulmonary fibrosis
      in mice, which is characterized by persistent progression of fibrosis in the
      chronic phase. Pranlukast (30 mg/kg/day) was administered orally to mice for 2 or
      10 weeks after intratracheal silica instillation. RESULTS: Pranlukast treatment
      for 10 weeks significantly attenuated the progression of pulmonary fibrosis, and
      decreased the content of CysLTs and LTB(4), which were markedly increased in the
      bronchoalveolar lavage fluid (BALF) and lung tissues of silica-instilled mice in
      the chronic phase. However, pranlukast treatment for 2 weeks neither affected the
      acute inflammatory response induced by silica instillation nor inhibited the
      onset of fibrosis. The expression of TGF-beta1 and TNF-alpha was not affected by
      pranlukast treatment for either 2 or 10 weeks. CONCLUSIONS: Pranlukast attenuates
      the progression of pulmonary fibrosis in the chronic phase but has no effect on
      the acute inflammatory response or on the onset of pulmonary fibrosis. The
      antifibrotic effect of pranlukast may be exhibited by antagonizing the direct
      profibrotic effect of CysLTs, without affecting the expression of other
      profibrotic cytokines such as TGF-beta1 and TNF-alpha, and also by decreasing the
      production of CysLTs and LTB(4).

PMID- 22378145
TI  - Evidence for a double dissociation of articulatory rehearsal and non-articulatory
      maintenance of phonological information in human verbal working memory.
AB  - OBJECTIVE: Recent functional neuroimaging studies have provided evidence that
      human verbal working memory is represented by two complementary neural systems, a
      left lateralized premotor-parietal network implementing articulatory rehearsal
      and a presumably phylogenetically older bilateral anterior-prefrontal/inferior
      parietal network subserving non-articulatory maintenance of phonological
      information. In order to corroborate these findings from functional neuroimaging,
      we performed a targeted behavioural study in patients with very selective and
      circumscribed brain lesions to key regions suggested to support these different
      subcomponents of human verbal working memory. METHODS: Within a sample of over
      500 neurological patients assessed with high-resolution structural magnetic
      resonance imaging, we identified 2 patients with corresponding brain lesions, one
      with an isolated lesion to Broca's area and the other with a selective lesion
      bilaterally to the anterior middle frontal gyrus. These 2 patients as well as
      groups of age-matched healthy controls performed two circuit-specific verbal
      working memory tasks. In this way, we systematically assessed the hypothesized
      selective behavioural effects of these brain lesions on the different
      subcomponents of verbal working memory in terms of a double dissociation.
      RESULTS: Confirming prior findings, the lesion to Broca's area led to reduced
      performance under articulatory rehearsal, whereas the non-articulatory
      maintenance of phonological information was unimpaired. Conversely, the
      bifrontopolar brain lesion was associated with impaired non-articulatory
      phonological working memory, whereas performance under articulatory rehearsal was
      unaffected. CONCLUSION: The present experimental neuropsychological study in
      patients with specific and circumscribed brain lesions confirms the hypothesized
      double dissociation of two complementary brain systems underlying verbal working
      memory in humans. In particular, the results demonstrate the functional relevance
      of the anterior prefrontal cortex for non-articulatory maintenance of
      phonological information and, in this way, provide further support for the
      evolutionary-based functional-neuroanatomical model of human working memory.

PMID- 22378146
TI  - NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral
      sclerosis.
AB  - Mutations in NIPA1 cause Hereditary Spastic Paraplegia type 6, a
      neurodegenerative disease characterized by an (upper) motor neuron phenotype.
      Deletions of NIPA1 have been associated with a higher susceptibility to
      amyotrophic lateral sclerosis (ALS). The exact role of genetic variation in NIPA1
      in ALS susceptibility and disease course is, however, not known. We sequenced the
      entire coding sequence of NIPA1 and genotyped a polyalanine repeat located in the
      first exon of NIPA1. A total of 2292 ALS patients and 2777 controls from three
      independent European populations were included. We identified two sequence
      variants that have a potentially damaging effect on NIPA1 protein function. Both
      variants were identified in ALS patients; no damaging variants were found in
      controls. Secondly, we found a significant effect of 'long' polyalanine repeat
      alleles on disease susceptibility: odds ratio = 1.71, P = 1.6 * 10(-4). Our
      analyses also revealed a significant effect of 'long' alleles on patient survival
      [hazard ratio (HR) = 1.60, P = 4.2 * 10(-4)] and on the age at onset of symptoms
      (HR = 1.37, P = 4.6 * 10(-3)). In patients carrying 'long' alleles, median
      survival was 3 months shorter than patients with 'normal' genotypes and onset of
      symptoms occurred 3.6 years earlier. Our data show that NIPA1 polyalanine repeat
      expansions are a common risk factor for ALS and modulate disease course.

PMID- 22378148
TI  - Long-term risk of recurrent peptic ulcer bleeding in patients with liver
      cirrhosis: a 10-year nationwide cohort study.
AB  - Peptic ulcer bleeding leads to substantial morbidity and mortality in patients
      with liver cirrhosis, but their long-term risk of recurrent bleeding remains
      elusive. This nationwide cohort study aimed to elucidate the association between
      cirrhosis and recurrent peptic ulcer bleeding by analyzing the Taiwan National
      Health Insurance Research Database. We enrolled a total of 9,711 patients who had
      cirrhosis with clinical complications of portal hypertension from all patients (n
      = 271,030) hospitalized for peptic ulcer bleeding between January 1997 and
      December 2006, along with 38,844 controls who were matched at a 1:4 proportion
      for age, sex, and antisecretory agents. We accounted for death as the competing
      cause of risk when calculating the cumulative incidences and hazard ratios of
      recurrent bleeding during the 10-year study period. Overall, patients with
      cirrhosis had a significantly higher death-adjusted rebleeding rate compared with
      controls (1 year, 14.4% versus 11.3%; 5 years, 26.1% versus 22.5%; 10 years,
      28.4% versus 27.1%; P < 0.001). The modified Cox proportional hazard model
      verified that cirrhosis was significantly associated with peptic ulcer rebleeding
      (adjusted hazard ratio, 3.19; 95% confidence interval, 2.62-3.88), but also
      uncovered a seemingly paradoxical interaction between cirrhosis and age.
      Multivariate stratified analysis further revealed that the rebleeding risk after
      adjustment for death diminished with age in patients with cirrhosis, whose risk
      of death far exceeded that of rebleeding when they grew old. CONCLUSION: Liver
      cirrhosis is associated with long-term risk of recurrent peptic ulcer bleeding,
      although the risk declines with age because of death being the competing cause.
      Effective therapy should be sought to reduce this excessive risk in these
      critically ill patients, particularly for those at younger age with longer life
      expectancy.

PMID- 22378147
TI  - Penetrance of biallelic SMARCAL1 mutations is associated with environmental and
      genetic disturbances of gene expression.
AB  - Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related,
      matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1)
      cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely
      penetrant autosomal recessive disorder. Using human, Drosophila and mouse models,
      we show that the proteins encoded by SMARCAL1 orthologs localize to
      transcriptionally active chromatin and modulate gene expression. We also show
      that, as found in SIOD patients, deficiency of the SMARCAL1 orthologs alone is
      insufficient to cause disease in fruit flies and mice, although such deficiency
      causes modest diffuse alterations in gene expression. Rather, disease manifests
      when SMARCAL1 deficiency interacts with genetic and environmental factors that
      further alter gene expression. We conclude that the SMARCAL1 annealing helicase
      buffers fluctuations in gene expression and that alterations in gene expression
      contribute to the penetrance of SIOD.

PMID- 22378150
TI  - NRF2 is overexpressed in ovarian epithelial carcinoma and is regulated by
      gonadotrophin and sex-steroid hormones.
AB  - Aberrant nuclear factor-erythroid 2 (NRF2) expression correlates with tumor
      development. We investigated NRF2 expression in ovarian epithelial carcinoma
      (OEC), aiming to identify associations with clinicopathological factors, hormones
      and induced reactive oxygen species (ROS). Immunohistochemical staining for NRF2
      expression was performed on 10 benign cystadenomas, 4 boderline tumors and 64
      OECs. Western blotting was used to determine the effects of hormones on NRF2
      expression in OEC. NRF2 protein was found to be overexpressed in OEC.
      Gonadotrophins and estrogen induced ROS production in OEC; these hormones also
      enhanced NRF2 expression. Therefore, aberrant expression may be induced by
      hormones through ROS signaling. Increased NRF2 expression may be a molecular
      event in OEC carcinogenesis.

PMID- 22378152
TI  - The role and impact of research agendas on the comparative-effectiveness research
      among antihyperlipidemics.
AB  - Although it is well established that funding source influences the publication of
      clinical trials, relatively little is known about how funding influences trial
      design. We examined a public trial registry to determine how funding source
      shapes trial design among trials involving antihyperlipidemics. We used an
      automated process to identify and analyze 809 trials from a set of 72,564. Three
      networks representing industry-, collaboratively, and non-industry-funded trials
      were constructed. Each network comprised 18 drugs as nodes connected according to
      the number of comparisons made between them. The results indicated that industry
      funded trials were more likely to compare across drugs and examine dyslipidemia
      as a condition, and less likely to register safety outcomes. The source of
      funding for clinical trials had a measurable effect on trial design, which helps
      quantify differences in research agendas. Improved monitoring of current clinical
      trials may be used to more closely align research agendas to clinical needs.

PMID- 22378151
TI  - Role of fibroblast growth factor 2 and Wnt signaling in anabolic effects of
      parathyroid hormone on bone formation.
AB  - Osteoporosis poses enormous health and economic burden worldwide. One of the very
      few anabolic agents for osteoporosis is parathyroid hormone (PTH). Although great
      progress has been made since the FDA approved PTH in 2002, the detailed
      mechanisms of the bone anabolic effects of intermittent PTH treatment is still
      not well understood. PTH bone anabolic effect is regulated by extracellular
      factors. Maximal bone anabolic effect of PTH requires fibroblast growth factor 2
      (FGF2) signaling, which might be mediated by transcription factor activating
      transcription factor 4 (ATF4). Maximal bone anabolic effect of PTH also requires
      Wnt signaling. Particularly, Wnt antagonists such as sclerostin, dickkopf 1
      (DKK1) and secreted frizzled related protein 1 (sFRP1) are promising targets to
      increase bone formation. Interestingly, FGF2 signaling modulates Wnt/beta-Catenin
      signaling pathway in bone. Therefore, multiple signaling pathways utilized by PTH
      are cross talking and working together to promote bone formation. Extensive
      studies on the mechanisms of action of PTH will help to identify new pathways
      that regulate bone formation, to improve available agents to stimulate bone
      formation, and to identify potential new anabolic agents for osteoporosis.

PMID- 22378153
TI  - A modeling and simulation approach to characterize methadone QT prolongation
      using pooled data from five clinical trials in MMT patients.
AB  - Pharmacokinetic (PK)-pharmacodynamic modeling and simulation were used to
      establish a link between methadone dose, concentrations, and Fridericia rate
      corrected QT (QTcF) interval prolongation, and to identify a dose that was
      associated with increased risk of developing torsade de pointes. A linear
      relationship between concentration and QTcF described the data from five clinical
      trials in patients on methadone maintenance treatment (MMT). A previously
      published population PK model adequately described the concentration-time data,
      and this model was used for simulation. QTcF was increased by a mean (90%
      confidence interval (CI)) of 17 (12, 22) ms per 1,000 ng/ml of methadone. Based
      on this model, doses >120 mg/day would increase the QTcF interval by >20 ms. The
      model predicts that 1-3% of patients would have DeltaQTcF >60 ms, and 0.3-2.0% of
      patients would have QTcF >500 ms at doses of 160-200 mg/day. Our predictions are
      consistent with available observational data and support the need for
      electrocardiogram (ECG) monitoring and arrhythmia risk factor assessment in
      patients receiving methadone doses >120 mg/day.

PMID- 22378155
TI  - Low-dose lisinopril in normotensive men with idiopathic oligospermia and
      infertility: a 5-year randomized, controlled, crossover pilot study.
AB  - The outcomes of drug treatment for male infertility remain conjectural, with
      controversial study results. Our pilot study employed a randomized, placebo
      controlled, crossover methodology with intention-to-treat analysis. Thirty-three
      men with idiopathic oligospermia were randomized to start either daily oral
      lisinopril 2.5 mg (n = 17) or daily oral placebo (n = 16). Lisinopril was found
      to cause a normalization of seminal parameters in 53.6% of the participants.
      Although the mean ejaculate volume was unchanged (P >= 0.093), the total sperm
      cell count and the percentage of motile sperm cells increased (P <= 0.03 and P <
      0.001, respectively), whereas the percentage of sperm cells with abnormal
      morphology decreased (P <= 0.04). The pregnancy rate was 48.5%, and there was no
      serious adverse drug event. It is concluded, albeit cautiously, that prolonged
      treatment with 2.5 mg/day of oral lisinopril may be well tolerated in
      normotensive men with idiopathic oligospermia, may improve sperm quantity and
      quality, and may enhance fertility in approximately half of those treated.

PMID- 22378156
TI  - Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism.
AB  - The cytochrome P450 (CYP) 2C9 R150H (*8) allele occurs commonly in African
      Americans and is associated with lower warfarin dose requirements. We conducted a
      pharmacokinetic study to examine whether the CYP2C9*8 allele impacts warfarin
      clearance in African-American patients. We also conducted an in vitro kinetic
      study of S-warfarin 7-hydroxylation using complementary DNA (cDNA)-expressed
      CYP2C9 enzymes. We observed a 30% reduction in the unbound oral clearance of S
      warfarin and a 25% lower R- to S-warfarin plasma concentration ratio in patients
      with the CYP2C9*8 allele (n = 12) as compared to CYP2C9*1 homozygotes (n = 26).
      Consistent with these findings, the in vitro intrinsic clearance of S-warfarin
      was 30% lower with the cDNA-expressed R150H protein as compared to the wild-type
      protein. These data show that the R150H variant protein expressed by the CYP2C9*8
      allele is associated with lower S-warfarin clearance. This finding provides
      clinical and experimental evidence to explain the lower warfarin dose
      requirements in patients with the CYP2C9*8 allele.

PMID- 22378158
TI  - Drug-induced PML: a global agenda for a global challenge.
AB  - The occurrence of severe adverse events such as progressive multifocal
      leukoencephalopathy (PML) has the potential to limit the benefits of highly
      efficacious medicines being developed to fulfill unmet clinical needs across
      therapeutic areas. Following an Expert meeting in London in July 2011
      (http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500111562.
      df), a research agenda, highlighting methodological, clinical, and communication
      elements, to mitigate the risk and improve the management of drug-induced PML has
      been agreed upon.

PMID- 22378157
TI  - Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype
      and abacavir dosing.
AB  - Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to
      immune cells and plays a critical role in normal immune recognition of pathogens.
      A variant allele, HLA-B*57:01, is associated with increased risk of a
      hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of
      genetic prescreening, hypersensitivity affects ~6% of patients and can be life
      threatening with repeated dosing. We provide recommendations (updated
      periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B
      genotype.

PMID- 22378159
TI  - Imaging of gastrointestinal absorption and biodistribution of an orally
      administered probe using positron emission tomography in humans.
AB  - The purpose of this study was to establish a method for imaging the process of
      gastrointestinal (GI) absorption and subsequent biodistribution in the human body
      after oral drug administration, using positron emission tomography (PET) with 2
      [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG). First, we developed a method to
      deliver the radiotracer safely into the stomach using soft gelatin capsules to
      avoid any significant exposure to the pharyngoesophageal region. Second, we
      performed pharmacokinetic (PK) analyses on time-radioactivity profiles in GI
      tissues and blood to calculate the gastric emptying and intestinal elimination
      rate constants and to estimate the fluid volume in the lumen of the small
      intestine from PET image analysis. This is the first study involving oral
      administration of a PET probe in humans, and the results demonstrate the high
      potential of PET technology to investigate the GI absorption and PK profiles of
      drugs in humans.

PMID- 22378160
TI  - Vardenafil-associated QTc changes: not merely a normal autonomic process.

PMID- 22378161
TI  - DFF45 expression in human endometrium is associated with menstrual cycle phases
      and decreases after menopause.
AB  - BACKGROUND: Human endometrium undergoes cyclic structural and functional
      modifications, and if no conception occurs menstruation is observed as the result
      of endometrial cell apoptosis via DFF40/DFF45 complex activation. In
      postmenopausal endometrium, the proliferative potential of endometrial cells is
      decreased, while their susceptibility to apoptosis increases. METHODS: The study
      group comprised 104 nonpregnant adult women (78 of reproductive age and 36 after
      menopause) with no neoplasm or hormonal treatment during the past 6 months.
      Immunohistochemistry and Western blot methods were used for DFF45 identification
      and semiquantitative assessment of its amount. RESULTS: Significantly more DFF45
      positive cells were detected in the endometrial glands compared to stroma, and
      this pattern was constant throughout the whole menstrual cycle and also present
      in postmenopausal endometrial species. The lowest mean relative amount of DFF45
      was detected in postmenopausal endometrial samples. In women of reproductive age,
      the highest mean relative amount of DFF45 was identified in an early secretory
      phase of the menstrual cycle, the lowest median value of the relative amount of
      DFF45 was observed in the late proliferative phase, and the difference was
      significant. CONCLUSION: The DFF45 level in human endometrium corresponds to the
      respective phase of the menstrual cycle and decreases significantly after
      menopause.

PMID- 22378162
TI  - Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with
      urea in critically ill patients.
AB  - BACKGROUND: Hyponatremia occurring as a result of the syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) is a common and potentially lethal
      complication in critically ill patients. Urea, by inducing renal water excretion
      and promoting sodium (Na) retention, has been well described as a treatment for
      chronic SIADH. However, there are limited data on its use for the treatment of
      SIADH as encountered in patients admitted to the intensive care unit (ICU). We
      assessed the effects of urea administration for treatment of SIADH in ICU
      patients. METHODS: Data from ICU patients treated with urea for SIADH between
      January 2000 and August 2010 were reviewed. The time courses of Na and urea
      concentrations were analyzed by variance analysis (ANOVA). RESULTS: Records from
      24 patients were analyzed. The most common etiology of SIADH was neurological (18
      patients). Before urea administration, the mean serum Na concentration was 124.8
      +/- 5.9 mEq/l. There was a significant increase in serum Na from the second day
      of treatment (131.4 +/- 3.5 mEq/l, p < 0.001) and a normalization of mean serum
      Na by the fourth day (136.2 +/- 4.1 mEq/l, p < 0.001). The mean serum urea
      concentration also increased (from 29.8 +/- 11.1 mg/dl before urea to 57.6 +/-
      24.0 mg/dl on the first day of treatment, p < 0.001). CONCLUSIONS: Urea
      administration appears useful for the treatment of SIADH-associated hyponatremia
      in critically ill patients. Prospective randomized controlled studies are needed
      to confirm these results.

PMID- 22378163
TI  - Pruritic poikilodermatous eruption associated with dermatomyositis: successful
      treatment with dapsone.

PMID- 22378164
TI  - Engineered 3D microporous gelatin scaffolds to study cell migration.
AB  - Here we present a facile method to fabricate microporous hydrogel scaffolds that
      can be functionalized with a chemokine gradient. These scaffolds allow studying
      cellular responses in a 3D environment.

PMID- 22378166
TI  - Gain control in the response of human visual cortex to plaids.
AB  - A recent intrinsic signal optical imaging study in tree shrew showed,
      surprisingly, that the population response of V1 to plaid patterns comprising
      grating components of equal contrast is predicted by the average of the responses
      to the individual components (MacEvoy SP, Tucker TR, Fitzpatrick D. Nat Neurosci
      12: 637-645, 2009). This prompted us to compare responses to plaids and gratings
      in human visual cortex as a function of contrast and orientation. We found that
      the functional MRI (fMRI) blood oxygenation level-dependent (BOLD) responses of
      areas V1-V3 to a plaid comprising superposed grating components of equal contrast
      are significantly higher than the responses to a single component. Furthermore,
      the orientation response profile of a plaid is poorly predicted from a linear
      combination of the responses to its components. Together, these results indicate
      that the model of MacEvoy et al. (2009) cannot, without modification, account for
      the fMRI BOLD response to plaids in human visual cortex.

PMID- 22378165
TI  - Diverse levels of an inwardly rectifying potassium conductance generate
      heterogeneous neuronal behavior in a population of dorsal cochlear nucleus
      pyramidal neurons.
AB  - Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that
      exhibit substantial variability in the expression levels of their ionic
      conductances. In contrast, the mechanisms, which generate heterogeneous neuronal
      behavior across a neuronal population, remain poorly understood. We addressed
      this problem in the dorsal cochlear nucleus, where principal neurons exist in two
      qualitatively distinct states: spontaneously active or not spontaneously active.
      Our studies reveal that distinct activity states are generated by the
      differential levels of a Ba(2+)-sensitive, inwardly rectifying potassium
      conductance (K(ir)). Variability in K(ir) maximal conductance causes variations
      in the resting membrane potential (RMP). Low K(ir) conductance depolarizes RMP to
      voltages above the threshold for activating subthreshold-persistent sodium
      channels (Na(p)). Once Na(p) channels are activated, the RMP becomes unstable,
      and spontaneous firing is triggered. Our results provide a biophysical mechanism
      for generating neural heterogeneity, which may play a role in the encoding of
      sensory information.

PMID- 22378167
TI  - Subthreshold somatic voltage in neocortical pyramidal cells can control whether
      spikes propagate from the axonal plexus to axon terminals: a model study.
AB  - There is suggestive evidence that pyramidal cell axons in neocortex may be
      coupled by gap junctions into an "axonal plexus" capable of generating very fast
      oscillations (VFOs) with frequencies exceeding 80 Hz. It is not obvious, however,
      how a pyramidal cell in such a network could control its output when action
      potentials are free to propagate from the axons of other pyramidal cells into its
      own axon. We address this problem by means of simulations based on three
      dimensional reconstructions of pyramidal cells from rat somatosensory cortex. We
      show that somatic depolarization enables propagation via gap junctions into the
      initial segment and main axon, while somatic hyperpolarization disables it. We
      show further that somatic voltage cannot effectively control action potential
      propagation through gap junctions on minor collaterals; action potentials may
      therefore propagate freely from such collaterals regardless of somatic voltage.
      In previous work, VFOs are all but abolished during the hyperpolarization phase
      of slow oscillations induced by anesthesia in vivo. This finding constrains the
      density of gap junctions on collaterals in our model and suggests that axonal
      sprouting due to cortical lesions may result in abnormally high gap junction
      density on collaterals, leading in turn to excessive VFO activity and hence to
      epilepsy via kindling.

PMID- 22378168
TI  - Sensitivity of EMG-EMG coherence to detect the common oscillatory drive to hand
      muscles in young and older adults.
AB  - Multichannel surface electromyograms (EMGs) were used to examine the sensitivity
      of EMG-EMG coherence to infer changes in common oscillatory drive to hand muscles
      in young and older adults. Previous research has shown that measures of coherence
      calculated from different neurophysiological signals are influenced by the age of
      the subject, the visual feedback provided to the subject, and the task being
      performed. The change in the magnitude of EMG-EMG coherence across experimental
      conditions is often interpreted as a change in the oscillatory drive to
      motoneuron pools of a pair of muscles. However, signal processing (e.g., full
      wave rectification) and electrode location are also reported to influence EMG-EMG
      coherence, which could decrease the sensitivity of EMG-EMG coherence to infer a
      change in common oscillatory drive to motoneurons. In this study, multichannel
      EMGs were used to compare EMG-EMG coherence in young (n = 11) and older (n = 10)
      adults during index finger abduction and pinch grip tasks performed at 2 and 3.5
      N with a low and a high visual feedback gain. We found that, across all
      conditions, EMG-EMG coherence was influenced by electrode location (P < 0.001)
      but not by subject age, visual feedback gain, task, or signal processing. These
      results suggest that EMG-EMG coherence is most sensitive to electrode location.
      The results are discussed in terms of the potential issues related to inferring a
      common oscillatory drive to hand muscles with surface EMGs.

PMID- 22378169
TI  - Development of state estimation explains improvements in sensorimotor performance
      across childhood.
AB  - Previous developmental research examining sensorimotor control of the arm in
      school-age children has demonstrated age-related improvements in movement
      kinematics. However, the mechanisms that underlie these age-related improvements
      are still unclear. This study hypothesized that changes in sensorimotor
      performance across childhood can be attributed, in part, to the development of
      state estimation, defined as estimates computed by the central nervous system,
      which specify both current and future hand positions and velocities (i.e., hand
      "state"). Two behavioral experiments were conducted, in which 6- to 12-year-old
      children and young adults executed goal-directed arm movements. Results from
      Experiment 1 revealed that young children (i.e., ~6-8 years) have less precise
      proprioceptive feedback for static (i.e., stationary) hand state estimation
      compared with older children (i.e., ~10-12 years), resulting in increased
      variability of target-directed reaching movements. Experiment 2 demonstrated that
      young children rely on delayed and unreliable state estimates during the
      execution of goal-directed hand movements (i.e., dynamic state estimation),
      resulting in both increased movement errors and directional variability.
      Collectively, these results suggest that improvements in sensorimotor behavior
      across childhood can be attributed, at least partially, to the development of
      both static and dynamic state estimation.

PMID- 22378170
TI  - Microstructural organizational patterns in the human corticostriatal system.
AB  - The axons that project into the striatum are known to segregate according to
      macroscopic cortical systems; however, the within-region organization of these
      fibers has yet to be described in humans. We used in vivo fiber tractography, in
      neurologically healthy adults, to map white matter bundles that originate in
      different neocortical areas, navigate complex fiber crossings, and project into
      the striatum. As expected, these fibers were generally segregated according to
      cortical origin. Within a subset of pathways, a patched pattern of inputs was
      observed, consistent with previous ex vivo histological studies. In projections
      from the prefrontal cortex, we detected a topography in which fibers from rostral
      prefrontal areas projected mostly to rostral parts of the striatum and vice versa
      for inputs originating in caudal cortical areas. Importantly, within this
      prefrontal system there was also an asymmetry in the subset of divergent
      projections, with more fibers projecting in a posterior direction than anterior.
      This asymmetry of information projecting into the basal ganglia was predicted by
      previous network-level computational models. A rostral-caudal topography was also
      present at the local level in otherwise somatotopically organized fibers
      projecting from the motor cortex. This provides clear evidence that the
      longitudinal organization of input fields, observed at the macroscopic level
      across cortical systems, is also found at the microstructural scale at which
      information is segregated as it enters the human basal ganglia.

PMID- 22378171
TI  - GABAA receptors increase excitability and conduction velocity of cerebellar
      parallel fiber axons.
AB  - In the adult mammalian brain, GABA(A) receptors (GABA(A)Rs) are responsible for
      the predominant forms of synaptic inhibition, but these receptors can excite
      neurons when the chloride equilibrium potential (E(Cl)) is depolarized. In many
      mature neurons, GABA(A)Rs are found on presynaptic terminals where they exert
      depolarizing effects. To understand whether excitatory GABA action affects axonal
      function, we used transverse cerebellar slices to measure the effects of
      photolysis of caged GABA on the initiation and propagation of compound parallel
      fiber (PF) action potentials (APs). Photolysis of caged GABA increased the
      amplitude and conduction velocity of PF APs; GABA reuptake blockers and a
      positive modulator of GABA(A)Rs enhanced these effects. In contrast, a modulator
      selective for delta-subunit-containing GABA(A)Rs did not enhance these effects
      and responsiveness remained in delta(-/-) mice, arguing that delta-subunit
      containing GABA(A)Rs are not required. Synaptically released GABA also increased
      PF excitability, indicating that the mechanism is engaged by physiological
      signals. A Hodgkin-Huxley-style compartmental model of the PF axon and granule
      cell body was constructed, and this model recapitulated the GABA-dependent
      decrease in AP threshold and the increase in conduction velocity, features that
      were sensitive to E(Cl) and to the voltage dependence of sodium channel
      inactivation. The model also predicts that axonal GABA(A)Rs could affect
      orthodromic spike initiation. We conclude that GABA acting on cerebellar PFs
      facilitates both spike generation and propagation, allowing axons of granule
      cells to passively integrate signals from inhibitory interneurons and influence
      information flow in the input layer to the cerebellar cortex.

PMID- 22378172
TI  - The brain matters: effects of descending signals on motor control.
AB  - The ability of nerve cords and spinal cords to exhibit fictive rhythmic
      locomotion in the absence of the brain is well-documented in numerous species.
      Although the brain is important for modulating the fictive motor output, it is
      broadly assumed that the functional properties of neuronal circuits identified in
      simplified preparations are conserved with the brain attached. We tested this
      assumption by examining the properties of a novel interneuron recently identified
      in the leech (Hirudo verbana) nerve cord. This neuron, cell E21, initiates and
      drives stereotyped fictive swimming activity in preparations of the isolated
      leech nerve cord deprived of the head brain. We report that, contrary to
      expectation, the motor output generated when cell E21 is stimulated in
      preparations with the brain attached is highly variable. Swim frequency and
      episode duration are increased in some of these preparations and decreased in
      others. Cell E21 controls swimming, in part, via excitatory synaptic interactions
      with cells 204, previously identified gating neurons that reliably initiate and
      strongly enhance leech swimming activity when the brain is absent. We found that
      in preparations with the brain present, the magnitude of the synaptic interaction
      from cell E21 to cell 204 is reduced by 50% and that cell 204-evoked responses
      also were highly variable. Intriguingly, most of this variability disappeared in
      semi-intact preparations. We conclude that neuronal circuit properties identified
      in reduced preparations might be fundamentally altered from those that occur in
      more physiological conditions.

PMID- 22378173
TI  - Cautious gait in relation to knowledge and vision of height: is altered visual
      information the dominant influence?
AB  - For some people, visual exposure creates difficulty with movement and balance,
      yet the mechanisms causing this are poorly understood. The altered visual
      environment is an obvious possible cause of degraded balance. We studied
      locomotion in normal healthy adults along a 22-cm-wide walkway at ground level
      and at a height of 3.5 m. This produced substantial changes in gait progression
      (velocity reduced by 0.34 ms(-1), P <0.01), proportion of time spent in double
      support more than doubled (P <0.01), and galvanic skin conductance, a measure of
      physiological arousal, increased significantly (P <0.01). Since increasing visual
      distance is known to destabilize balance, our primary question was whether the
      disturbing effects of height could be eliminated by replacing sight of the drop
      with a visual surround comparable to ground level while retaining the danger and
      knowledge of the risk. Removing visual exposure did not significantly change the
      gait progression (P = 0.65) or double support duration (P = 0.58) but produced a
      small, significant reduction in physiological arousal (P = 0.04). In response to
      postural threat, knowledge of danger rather than current visual environment was
      the dominant cause of cautious gait and elevated physiological arousal in
      response to postural threat. We conclude that the mechanisms disturbing
      locomotion, balance, and autonomic response occur at a high task level which
      integrates cognition and prior experience with sensory input.

PMID- 22378175
TI  - Temporal precision and reliability in the velocity regime of a hair-cell sensory
      system: the mechanosensory lateral line of goldfish, Carassius auratus.
AB  - Fish and aquatic frogs detect minute water motion by means of a specialized
      mechanosensory system, the lateral line. Ubiquitous in fish, the lateral-line
      system is characterized by hair-cell based sensory structures across the fish's
      surface called neuromasts. These neuromasts occur free-standing on the skin as
      superficial neuromasts (SN) or are recessed into canals as canal neuromasts. SNs
      respond to rapid changes of water velocity in a small layer of fluid around the
      fish, including the so-called boundary layer. Although omnipresent, the boundary
      layer's impact on the SN response is still a matter of debate. For the first time
      using an information-theoretic approach to this sensory system, we have
      investigated the SN afferents encoding capabilities. Combining covariance
      analysis, phase analysis, and modeling of recorded neuronal responses of primary
      lateral line afferents, we show that encoding by the SNs is adequately described
      as a linear, velocity-responsive mechanism. Afferent responses display a bimodal
      distribution of opposite Wiener kernels that likely reflected the two hair-cell
      populations within a given neuromast. Using frozen noise stimuli, we further
      demonstrate that SN afferents respond in an extremely precise manner and with
      high reproducibility across a broad frequency band (10-150 Hz), revealing that an
      optimal decoder would need to rely extensively on a temporal code. This was
      further substantiated by means of signal reconstruction of spike trains that were
      time shifted with respect to their original. On average, a time shift of 3.5 ms
      was enough to diminish the encoding capabilities of primary afferents by 70%. Our
      results further demonstrate that the SNs' encoding capability is linearly related
      to the stimulus outside the boundary layer, and that the boundary layer can,
      therefore, be neglected while interpreting lateral line response of SN afferents
      to hydrodynamic stimuli.

PMID- 22378174
TI  - Cerebrovascular responses of the rat brain to noxious stimuli as examined by
      functional near-infrared whole brain imaging.
AB  - While near-infrared (NIR) spectroscopy has been increasingly used to detect
      stimulated brain activities with an advantage of dissociating regional oxy- and
      deoxyhemoglobin concentrations simultaneously, it has not been utilized much in
      pain research. Here, we investigated and demonstrated the feasibility of using
      this technique to obtain whole brain hemodynamics in rats and speculated on the
      functional relevance of the NIR-based hemodynamic signals during pain processing.
      NIR signals were emitted and collected using a 26-optodes array on rat's dorsal
      skull surface after the removal of skin. Following the subcutaneous injection of
      formalin (50 MUl, 3%) into a hindpaw, several isolable brain regions showed
      hemodynamic changes, including the anterior cingulate cortex, primary/secondary
      somatosensory cortexes, thalamus, and periaqueductal gray (n = 6). Time courses
      of hemodynamic changes in respective regions matched with the well-documented
      biphasic excitatory response. Surprisingly, an atypical pattern (i.e., a decrease
      in oxyhemoglobin concentration with a concomitant increase in deoxyhemoglobin
      concentration) was seen in phase II. In a separate group of rats with innocuous
      brush and noxious pinch of the same area (n = 11), results confirmed that the
      atypical pattern occurred more likely in the presence of nociception than
      nonpainful stimulation, suggesting it as a physiological substrate when the brain
      processes pain. In conclusion, the NIR whole brain imaging provides a useful
      alternative to study pain in vivo using small-animal models. Our results support
      the notion that neurovascular response patterns depend on stimuli, bringing
      attention to the interpretation of vascular-based neuroimaging data in studies of
      pain.

PMID- 22378176
TI  - Changes in motor unit recruitment thresholds of the human anconeus muscle during
      torque development preceding shortening elbow extensions.
AB  - Rate of torque development and the subsequent movement velocity are modulated by
      motor unit (MU) properties, primarily MU discharge rate and MU recruitment
      threshold (MURT). In isometric conditions, MURTs have been shown to decrease with
      increased rates of torque development. It is unclear whether this relationship is
      similar in the production of dynamic shortening contractions. Using fast joint
      velocities to drive the system, we aimed to determine how anconeus MURTs recorded
      during the torque production phase preceding movement were affected in relation
      to the resultant peak elbow extension velocity. Recruitment thresholds of 17 MUs
      from 9 young men were tracked throughout non-isokinetic dynamic elbow extensions
      with velocities ranging from 64 degrees /s to 500 degrees /s at a constant
      resistance of 25% of maximal voluntary isometric contraction and during isometric
      elbow extensions (0 degrees /s). Relative MURTs decreased ~50% from the slowest
      (<25% of maximal velocity) to the fastest (>75% of maximal velocity) resultant
      velocity ranges (P < 0.05). Although a significant (P < 0.001) but weak (r = 
      0.27, R(2) = 0.08) relationship was observed between MURT and resultant peak
      elbow extension velocity for the group, only 7 of the 17 MUs displayed
      significant moderate (r = -0.40, R(2) = 0.17) to strong (r = -0.85, R(2) = 0.73)
      negative MURT-velocity relationships. These data indicate variable responses of
      MURTs with increasing resultant peak velocity, which may be related to the
      intrinsic properties of individual MUs.

PMID- 22378179
TI  - A computational study of the enantioselective addition of n-BuLi to benzaldehyde
      in the presence of a chiral lithium N,P amide.
AB  - In the presence of a chiral lithium N,P amide, alkylation of benzaldehyde results
      in an enantioselective formation of 1-phenyl-pentanol. This stereoselective
      addition reaction has herein been studied using dispersion-corrected density
      functional theory. For five different chiral ligands originating from amino acids
      the resulting enantioselectivity has been computationally determined and compared
      with experimentally available enantiomeric ratios (e.r.). In all cases the
      experimentally preferred enantiomer could be reproduced by the computational
      model. The selectivity trend among the ligands was found strongly sensitive to
      the amount of dispersion correction included. The origin of selectivity in the
      alkylation reaction is found to be composed of many combined interactions. For
      the most selective ligand 2A the most important factors found, which are
      favouring the (R)-TS, are a CH-pi interaction between benzaldehyde-dimethyl ether
      (DME), stronger Li-solvation, and Li-pi interactions with the phenyl ring in the
      backbone of the chiral lithium N,P amide. In addition, solvation by the bulk
      solvent and the size of the substituent on the nitrogen are also found important
      factors for the enantioselectivity.

PMID- 22378177
TI  - Modulating locomotor adaptation with cerebellar stimulation.
AB  - Human locomotor adaptation is necessary to maintain flexibility of walking.
      Several lines of research suggest that the cerebellum plays a critical role in
      motor adaptation. In this study we investigated the effects of noninvasive
      stimulation of the cerebellum to enhance locomotor adaptation. We found that
      anodal cerebellar transcranial direct current stimulation (tDCS) applied during
      adaptation expedited the adaptive process while cathodal cerebellar tDCS slowed
      it down, without affecting the rate of de-adaptation of the new locomotor
      pattern. Interestingly, cerebellar tDCS affected the adaptation rate of spatial
      but not temporal elements of walking. It may be that spatial and temporal control
      mechanisms are accessible through different neural circuits. Our results suggest
      that tDCS could be used as a tool to modulate locomotor training in neurological
      patients with gait impairments.

PMID- 22378178
TI  - Quantitative unit classification of ventral tegmental area neurons in vivo.
AB  - Neurons in the ventral tegmental area (VTA) synthesize several major
      neurotransmitters, including dopamine (DA), GABA, and glutamate. To classify VTA
      single-unit neural activity from freely moving rats, we used hierarchical
      agglomerative clustering and probability distributions as quantitative methods.
      After many parameters were examined, a firing rate of 10 Hz emerged as a
      transition frequency between clusters of low-firing and high-firing neurons. To
      form a subgroup identified as high-firing neurons with GABAergic characteristics,
      the high-firing classification was sorted by spike duration. To form a subgroup
      identified as putative DA neurons, the low-firing classification was sorted by DA
      D2-type receptor pharmacological responses to quinpirole and eticlopride.
      Putative DA neurons were inhibited by the D2-type receptor agonist quinpirole and
      returned to near-baseline firing rates or higher following the D2-type receptor
      antagonist eticlopride. Other unit types showed different responses to these D2
      type receptor drugs. A multidimensional comparison of neural properties indicated
      that these subgroups often clustered independently of each other with minimal
      overlap. Firing pattern variability reliably distinguished putative DA neurons
      from other unit types. A combination of phasic burst properties and a low skew in
      the interspike interval distribution produced a neural population that was
      comparable to the one sorted by D2 pharmacology. These findings provide a
      quantitative statistical approach for the classification of VTA neurons in
      unanesthetized animals.

PMID- 22378180
TI  - An explicitly correlated Mukherjee's state specific coupled cluster method:
      development and pilot applications.
AB  - This paper reports development of the explicitly correlated variant of
      Mukherjee's state specific multireference coupled cluster method (MkCC-F12). The
      current implementation is restricted to conventional single and double
      excitations and to pseudo-double excitations related to the Slater Type Geminal
      (STG) correlation factor using the SP ansatz. The performance of the MkCCSD-F12
      was tested on calculations of singlet methylene, dissociation curve of the
      fluorine molecule, and the BeH(2) insertion pathway. As expected, the results of
      the newly developed method reconfirm the significantly faster convergence with
      respect to the basis set limit compared to the traditional expansion in Slater
      determinants. Results prove that treating the correlation factor separately for
      each reference is appropriate.

PMID- 22378182
TI  - Cardiac magnetic resonance imaging in Danon disease.
AB  - Danon disease is a rare X-linked dominant metabolic disorder caused by a primary
      deficiency in lysosome-associated membrane protein 2. It is characterized by the
      development of cardiac disease, skeletal myopathy and cognitive disorder. Due to
      the rarity of Danon disease, physicians may be unfamiliar with the phenotype,
      confusing it with hypertrophic cardiomyopathy or other causes of left ventricular
      hypertrophy. The present report demonstrates the clinical value of cardiac
      magnetic resonance imaging for the diagnostic work-up of Danon disease.

PMID- 22378183
TI  - Virotherapy of neuroendocrine tumors.
AB  - Most patients with small intestinal neuroendocrine tumors (SI-NETs), also
      referred to as midgut carcinoids, present with systemic disease at the time of
      diagnosis with metastases primarily found in regional lymph nodes and the liver.
      Curative treatment is not available for these patients and there is a need for
      novel and specific therapies. Engineered oncolytic viruses may meet the need and
      play an important role in the future management of SI-NET liver metastases. This
      review focuses on adenovirus as the oncolytic anti-cancer agent and its potential
      curative role for SI-NET liver metastases, but it also summarizes the use of
      oncolytic viruses for NETs in general. It discusses how specific features of
      neuroendocrine cell biology can be used to engineer viruses to become selective
      for infection of NET cells and/or replication within NET cells. In addition, it
      points out the advantages and shortcomings of using replicating viruses in the
      treatment of cancer and addresses research fields that can increase the efficacy
      of virus-based therapy.

PMID- 22378184
TI  - Healthcare financing in Syria: satisfaction with the current system and the role
      of national health insurance--a qualitative study of householders' views.
AB  - This study aims to identify the satisfaction with the current public health
      system and health benefit schemes, examine willingness to participate in national
      health insurance and review expectations and preferences of national health
      insurance. To this end, qualitative semi-structured interviews were carried out
      with 19 Syrian householders. Our results show that a need for health reform
      exists and that Syrian people are willing to support a national health insurance
      scheme if some key issues are properly addressed. Funding of the scheme is a
      major concern and should take into account the ability to pay and help the poor.
      In addition, waiting times should be shortened and sufficient coverage
      guaranteed. On the whole, the people would support a national health insurance
      with national pooling and purchasing under a public set-up, but important
      concerns of such a system regarding corruption and inefficiency were voiced too.
      Installing a quasi non-governmental organisation as manager of the insurance
      system under the stewardship of the Ministry of Health could provide a compromise
      acceptable to the people.

PMID- 22378185
TI  - Charged behaviour from neutral ligands: synthesis and properties of N
      heterocyclic pseudo-amides.
AB  - Deprotonation of the 1-isopropyl-3-(phenylamino)pyridin-1-ium iodide gives the
      corresponding neutral betaine, which is formalised as a pyridinium-amido ligand
      when coordinated to a metal. Spectroscopic, structural and theoretical methods
      have been used to investigate the metal-ligand bonding, ligand dynamics and
      electron distribution. Collectively, the data show that the ligand can be
      characterised as a pseudo-amide and is a strong donor akin to alkyl phosphines
      and N-heterocyclic carbenes. Furthermore, rotation about both N substituent C-N
      bonds occurs, which is in contrast to the two alternative pyridinium positional
      isomers that exhibit neutral resonance structures. For comparison, compounds and
      complexes derived from norharman were prepared, which contain an additional C-C
      bond supporting conjugation and the accessibility of a neutral resonance
      structure. Notwithstanding the formal neutral structure, norharman-derived
      ligands are comparably strong donors, and have the additional advantage of
      exhibiting stability to dioxygen and water.

PMID- 22378186
TI  - Tumorigenicity of cancer stem-like cells derived from hepatocarcinoma is
      regulated by microRNA-145.
AB  - microRNAs are implicated in cancer initiation and progression by their ability to
      affect the expression of genes and proteins that regulate cell proliferation and
      death. Recent studies found that the stem cell-related genes Sox2, Oct4 and Klf4
      are among the target genes regulated by microRNA-145 (miR-145), suggesting that
      miR-145 possibly plays a role in the maintenance of cancer stem cells. Therefore,
      it is important to address the involvement of miR-145 in the key roles of cancer
      stem cells in cancer initiation, progression and reoccurrence. We compared miR
      145 expression in the cancer stem-like cells (T3A-A3) derived from
      hepatocarcinoma, in the hepatocarcinoma cell line BEL-7402 and in the normal
      liver sinusoidal endothelial cell line (LSEC). As demonstrated by a TaqMan
      microRNA real-time assay, T3A-A3 cells express lower miR-145 levels compared to
      the other cell lines. To address the role of miR-145 in cancer stem cells, miR
      145 was restored in T3A-A3 cells. This resulted in senescence-like G1 arrest in
      cell cycling, and significantly inhibited clonogenic cell expansion in vitro and
      xenograft tumor growth in vivo. Moreover, miR-145 restoration diminished
      tumorsphere growth of T3A-A3 cells in vitro and T3A-A3 cells tumor formation in
      nude mice in vivo. Additionally, the increase in miR-145 levels paralleled the
      decrease in Oct4 levels. The effect of miR-145 on tumor suppression in T3A-A3
      cells was partly reversed by overexpression of Oct4 both in vitro and in vivo.
      Collectively, our data indicate that miR-145 plays an important role in cancer
      stem cell tumorigenicity, potentially via modulation of the downstream target,
      Oct4.

PMID- 22378187
TI  - Interface properties of ionic liquids containing metal ions: features and
      potentialities.
AB  - Interfaces and surfaces are the regions where important events happen: catalysis,
      molecular recognition, charge transfer, polymerization, and many other critical
      processes take place at the boundary between one medium and another. In this
      article we discuss the interface (liquid/air) properties of ionic liquids (ILs)
      containing dissolved metal ions with the aim to show the possibility to use metal
      salts to transform ILs and their surfaces into engineered liquid supports to
      apply in material sciences, separation procedures or to use as optical devices.

PMID- 22378188
TI  - Redox reaction in two-dimensional porous coordination polymers based on
      ferrocenedicarboxylates.
AB  - A series of 1,1'-ferrocenedicarboxylate-based two-dimensional porous coordination
      polymers were synthesized by incorporating different diamine co-ligands. These
      compounds immobilized on electrodes, exhibited reversible redox reactions,
      arising from ferrocenyl moiety.

PMID- 22378189
TI  - Unmasking the immune recognition of prostate cancer with CTLA4 blockade.
AB  - Although cancer cells can be immunogenic, tumour progression is associated with
      the evasion of immunosurveillance, the promotion of tumour tolerance and even the
      production of pro-tumorigenic factors by immune cells. Cytotoxic T lymphocyte
      associated antigen 4 (CTLA4) represents a crucial immune checkpoint, the blockade
      of which can potentiate anti-tumour immunity. CTLA4-blocking antibodies are now
      an established therapeutic approach for malignant melanoma, and clinical trials
      with CTLA4-specific antibodies in prostate cancer have also shown clinical
      activity. This treatment may provide insights into the targets that the immune
      system recognizes to drive tumour regression, and could potentially improve both
      outcome and toxicity for patients with prostate cancer.

PMID- 22378190
TI  - The determinants of tumour immunogenicity.
AB  - Many standard and targeted therapies, as well as radiotherapy, have been shown to
      induce an anti-tumour immune response, and immunotherapies rely on modulating the
      host immune system to induce an anti-tumour immune response. However, the immune
      response to such therapies is often reliant on the immunogenicity of a tumour.
      Tumour immunogenicity varies greatly between cancers of the same type in
      different individuals and between different types of cancer. So, what do we know
      about tumour immunogenicity and how might we therapeutically improve tumour
      immunogenicity? We asked four leading cancer immunologists around the world for
      their opinions on this important issue.

PMID- 22378191
TI  - Metabolism: unmasking an oncometabolite.

PMID- 22378192
TI  - A human claudin-1-derived peptide inhibits hepatitis C virus entry.
AB  - Hepatitis C virus (HCV) entry is a complicated process that requires multiple
      host factors, such as CD81, scavenger receptor BI, claudin-1 (CLDN1), and
      occludin. The interaction of virus and cellular entry factors represents a
      promising target for novel anti-HCV drug development. In this study, we sought to
      identify peptide inhibitors for HCV entry by screening a library of overlapping
      peptides covering the four above-mentioned entry factors. An 18-amino acid
      peptide (designated as CL58) that was derived from the CLDN1 intracellular and
      first transmembrane region inhibited both de novo and established HCV infection
      in vitro. Unlike previously reported peptides corresponding to CLDN1
      extracellular loops, CL58 did not alter the normal distribution of CLDN1 and was
      not cytotoxic in vitro at concentrations nearly 100-fold higher than the
      effective antiviral dose. The inhibitory effect of CL58 appeared to occur at a
      late step during viral entry, presumably after initial binding. Finally,
      overexpressed CL58 was able to interact with HCV envelope proteins. CONCLUSION:
      We identified a novel CLDN1-derived peptide that inhibits HCV entry at a
      postbinding step. The findings expand our knowledge of the roles that CLDN1 play
      in HCV entry and highlight the potential for developing a new class of inhibitors
      targeting the viral entry process.

PMID- 22378193
TI  - Cannabis-induced depersonalization disorder in adolescence.
AB  - We present a case series of 6 patients who developed persistent depersonalization
      disorder in adolescence after consuming cannabis. In 2 of these cases, the
      illness course was severely disabling. Within the growing body of literature that
      investigates the effects of cannabis use on mental health, the association
      between cannabis and depersonalization disorder is widely neglected. We review
      the clinical characteristics of this disorder and summarize the neurobiological
      evidence relating it to cannabis use. This case series extends awareness about
      the potentially detrimental effect of cannabis use in young individuals beyond
      its well-documented relationship with psychosis and other psychological sequelae.

PMID- 22378194
TI  - Nanog regulates molecules involved in stemness and cell cycle-signaling pathway
      for maintenance of pluripotency of P19 embryonal carcinoma stem cells.
AB  - To identify potential downstream targets of Nanog, a key transcription factor in
      the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma
      (EC) cells, global gene expression profiles in Nanog small interfering RNA
      (siRNA)-transfected P19 EC stem cells were performed using cDNA, 60-mer, and 30
      mer microarray platforms. The putative Nanog target genes identified by Nanog
      silencing were verified using reverse transcription-polymerase chain reaction
      after Nanog overexpression. Downregulation of Nanog in P19 cells resulted in
      reduction of pluripotency markers, such as Fgf4, Klf2, Mtf2, Oct-4, Rex1, Sox1,
      Yes, and Zfp143, whereas overexpression of Nanog in P19 cells reversely
      upregulated their expression. However, expressions of pluripotency markers
      Cripto, germ cell nuclear factor, Sox2, and Zfp57 as well as leukemia inhibitory
      factor (LIF)/Stat3 pathway molecules LIF, IL6st, and Stat3 were not affected
      after 48 h transfection with Nanog siRNA or construct. Nanog silencing also
      downregulated expression of molecules involved in the p53- and cell cycle
      signaling pathway (Atf3, Jdp2, Cul3, Hist1hic, and Bcl6), whereas expression of
      E2f1, Tob1, Lyn, and Smarcc1 was upregulated by Nanog silencing. Expressions of
      cyclins D1, D2, D3, and E1 as well as cyclin-dependent kinase (Cdk) 1 and Cdk6
      were downregulated by Nanog silencing in P19 cells, whereas Nanog overexpression
      reversely increased their expressions. Taken together, examination of global
      transcriptional changes after Nanog silencing followed by verification by Nanog
      overexpression has revealed new molecules involved in the maintenance of self
      renewal and in the regulation of the p53- and cell cycle-pathway of P19 cells.

PMID- 22378195
TI  - Outbreak of bullous impetigo caused by Staphylococcus aureus strains of phage
      type 3C/71 in a maternity ward linked to nasal carriage of a healthcare worker.
AB  - We describe an outbreak of bullous impetigo (BI) that occurred in a maternity
      unit and show phenotypic and genotypic properties and relatedness of isolated
      Staphylococcus aureus strains. Clinical material was obtained from 11 affected
      neonates. Additionally, nasal swabs from 67 healthy care workers (HCWs) as well
      as 107 environmental swabs were investigated. All isolates were screened for
      exfoliative toxin genes (eta, etb), antibiotic susceptibility and phage typed.
      Chromosomal DNA was genotyped by MLVF method and PCR/RFLP of coagulase gene were
      tested. Affected neonates were infected by two clusters of eta-positive S. aureus
      of phage type 3C/71: (1) MLVF type A isolates resistant only to penicillin, and
      (2) MLVF type B isolates resistant to penicillin and erythromycin/clindamycin.
      All isolates were susceptible to methicillin. We found 19 of 67 HCWs to be S.
      aureus nasal carriers. Two nasal isolates from HCWs were related to the outbreak
      on the basis of phage typing, PCR detection of eta/etb genes, antibiotyping and
      genotyping. Additionally, environmental swabs from the maternity unit revealed a
      3C/71 S. aureus in the mattress of a baby bed. This is the first documented case
      of an outbreak of BI caused by phage type 3C/71 eta-positive strain of S. aureus.

PMID- 22378196
TI  - Bioinspired organocatalytic asymmetric reactions.
AB  - Several small organic molecule catalysts are reminiscent of natural enzymes in
      their mode of action and substrate interaction/activation. This striking
      similarity has been a great source of inspiration for the development of new
      organocatalytic asymmetric processes. A few representative examples, mostly
      dealing with catalysts interacting through multiple hydrogen-bonds (synthetic
      oxyanion holes), are highlighted in this perspective.

PMID- 22378197
TI  - An integrated approach to data management, risk assessment, and decision making.
AB  - This paper describes a methodology called Risk Analysis, Communication,
      Evaluation, and Reduction (RACER) that converts environmental data directly to
      human health risk to enhance decision making and communication. The methodology
      was developed and implemented following the Cerro Grande fire in New Mexico that
      burned approximately 7,500 acres of Los Alamos National Laboratory in May 2000.
      The absence of a coordinated and comprehensive approach to managing and
      understanding environmental data was a major weakness in the responding agencies'
      ability to make and communicate decisions. RACER consists of three basic
      elements: managing information, converting information to knowledge, and
      communicating knowledge to decision makers and stakeholders. Data are maintained
      in a web-accessible database that accepts data as they are validated and
      uploaded. The user can select data for evaluation and convert them to knowledge
      using human health risk as a benchmark for ranking radionuclides, chemicals,
      pathways, or other criteria needed to make decisions. Knowledge about risk is
      communicated using graphic and tabular formats. The process is transparent,
      flexible, and rapid, which enhances credibility and trust among decision makers
      and stakeholders. The fundamental principles used in RACER can be applied
      anywhere radionuclides or chemicals are present in the environment.

PMID- 22378198
TI  - Linear dimensions and volumes of human lungs obtained from CT images.
AB  - This work provides the results of a collaboration between the Human Monitoring
      Laboratory (HML) and the Centre Hospitalier de l'Universite de Montreal (CHUM) in
      which CHUM provided CT lung image sets from 166 patients for the analysis of
      linear dimensions and lung volume. This work has shown that a large amount of
      data exists in the medical community that can be of value to the health physics
      community. The intent of this study was to determine the range of linear
      dimensional parameters that could be used for torso phantom development for males
      and females; understand and characterize the variability of linear lung
      dimensions for males and females; replace the brief table in ICRP 23 with more
      modern data for males and females; identify an empirical formula that would
      predict linear dimensions of human lungs from age, height and/or weight for males
      and females; characterize the left, right, and total lung volumes of males and
      females in this data set; and compare the lung volumes of males and females to
      published equations for determining lung volumes. It was found that linear
      dimensions of lungs are essentially independent of age, height, and weight, so
      predictive equations cannot be formulated; however, the ranges of those
      parameters have now been established for the population studied herein. The data
      presented here are more modern than the brief table that appeared in ICRP 23, and
      the average values could be used as future guidelines. Whole lung volumes have
      been determined from the voxel lung phantoms, and empirical formulae have been
      developed for males and females in this data set; these compare favorably with
      the published values in ICRP 66.

PMID- 22378199
TI  - Perceived risk of nuclear power and other risks during the last 25 years in
      Japan.
AB  - The present study described the results of three "fixed-point" surveys on
      perceived risk related to a list of social and individual risk events during 25
      years in Japan. Female clerical staff and researchers were asked to rank 30 items
      related to various types of technologies and human activities according to their
      subjective judgments on the order of perceived magnitude of risk in 1983, 1992,
      and 2007. A similar survey was undertaken for Japanese citizens using web-based
      questionnaires in 2007. In general, the risk perceptions of the Japanese people,
      irrespective of gender, age, and occupation, have been uniform during the last 25
      years. The female clerical staffs have consistently judged nuclear power as most
      risky during the last 25 years, whereas researchers' judgment fluctuated with
      events such as the Chernobyl accident. The ranking of the risk of motor vehicles
      fell during the 25-y period, whereas those of health risks with food
      preservatives, x-rays, and antibiotics rose transiently in the 1992 survey.
      During the 15 years from 1992 to 2007, people tended to learn how to accommodate
      themselves to these technologies with low risks in exchange for high benefits,
      except in the case of nuclear power. Nuclear power was regarded as a high-risk
      item by the Japanese even before the Fukushima nuclear power plant accident in
      March 2011. This partly explains that the crisis inevitably provokes further high
      risk perception in Japan, although the overall health threat to the human
      population in Japan is estimated to be relatively limited so far.

PMID- 22378200
TI  - Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation
      from selected severe 235U or 239Pu criticality accidents in USSR, United States,
      and Argentina.
AB  - Eight of the most severe cases of acute radiation disease (ARS) known to have
      occurred in humans (as the result of criticality accidents) had survival times
      less than 120 h (herein defined as "early death"). These accidents were analyzed
      and are discussed with respect to the specific accident scenarios and the
      resulting accident-specific, mixed neutron-gamma radiation clinical dose
      distributions. This analysis concludes that the cardiovascular system appears to
      be the most critical organ system failure for causing "early death" following
      approximate total body, mixed gamma-neutron radiation doses greater than 40-50
      Gy. The clinical data also suggest that there was definite chest dose dependence
      in the resulting survival times for these eight workers, who unfortunately
      suffered profound radiation injury and unusual clinical effects from such high
      dose radiation exposures. In addition, "toxemic syndrome" is correlated with the
      irradiation of large volumes of soft tissues. Doses to the hands or legs greater
      than 80-100 Gy or radiation lung injury also play significant but secondary roles
      in causing "early death" in accidents delivering chest doses greater than 50 Gy.

PMID- 22378201
TI  - Measurements of (60)Co in massive steel samples exposed to the Hiroshima atomic
      bomb explosion.
AB  - To study discrepancies in retrospective Hiroshima dosimetry, the specific
      activity of (60)Co in 16 steel samples from Hiroshima was measured using gamma
      ray spectrometry in underground laboratories. There is general agreement between
      these new activity measurements and the specific activities derived from
      previously calculated dose values on the one hand and former measurements of
      samples gathered at distances less than 1,000 m from the center of the explosion
      (< 1,000 m slant range) on the other. It was found that activities at long range
      (> 1,300 m slant range) were mainly cosmogenically induced. Furthermore, at long
      range, these results are in disagreement with older measurements whose specific
      activity values were 10 to 100 times higher than predicted by computer model
      calculations in DS86 and DS02. As a consequence, the previously reported
      discrepancy is not confirmed.

PMID- 22378202
TI  - Estimation of high-level, rapidly-changing concentrations using moving-filter
      continuous particulate air monitors.
AB  - A previously published mathematical model for the dynamic response of moving
      filter continuous particulate air monitors has been enhanced to extend that model
      to include decay chains. During this work, it was observed that a quantitative
      relationship appeared to exist between the monitor count rate and the time
      dependent particulate airborne radioactive material concentration if, and only
      if, the filter (tape) speed was much faster than the nominal 2.54 cm h(-1) (1 in
      h(-1)). The extended model demonstrated that operating moving-filter monitors at
      this nominal filter speed does not provide a quantitative measurement of a
      changing airborne particulate concentration of a fission product or other
      contaminant. By contrast, at faster filter speeds [e.g., 76.2 or 152.4 cm h(-1)
      (30 or 60 in h(-1))], numerical experimentation with this model showed that the
      count rate trace has essentially the same shape as the concentration profile. It
      was then found that a quantitative relationship applies, but only when the filter
      speed is sufficiently fast so that a Taylor series expansion of the monitor count
      rate can be reasonably well truncated at the first-order term. This mode of
      operation, which does not require any new monitor hardware, is capable of
      tracking rapidly changing concentrations. Since the fast filter speed also
      reduces the monitor's count rate, all else being equal, the approach will best be
      used for relatively high-level concentrations, such as may occur in abnormal or
      "accident" conditions. The count rate suppression may also be useful for reducing
      the detector saturation that can occur with higher levels of airborne particulate
      radioactivity in post-accident situations.

PMID- 22378203
TI  - An intercomparison for NIRS and NYU passive thoron gas detectors at NYU.
AB  - An intercomparison on thoron ((220)Rn) measurement was carried out between
      National Institute of Radiological Sciences, Japan (NIRS), and New York
      University School of Medicine, USA (NYU). The measurements of (220)Rn
      concentration at NIRS and NYU were performed by using the scintillation cell
      method and the two-filter method, respectively, as the standard measurement
      method. Three types of alpha track detectors based on passive radon ((222)Rn)
      (220)Rn discriminative measurement technique were used: Raduet and Radopot
      detectors were used at NIRS, and four-leaf detectors were used at NYU. In this
      study, the authors evaluated (220)Rn concentration variation in terms of run for
      exposure, measurement method, and exposure chamber. The detectors were exposed to
      (220)Rn gas with approximately 15 kBq m(-3) during the period from 0.75 to 3 d.
      As a result, the variation of each measurement method among these exposure runs
      was comparable to or less than that for the two-filter method. Agreement between
      the standard measurement methods of NIRS and NYU was observed to be about 10%, as
      is the case with the passive detectors. The Raduet detector showed a large
      variation in the detection response between the NIRS and NYU chambers, which
      could be related to different traceability.

PMID- 22378204
TI  - A biomathematical model of lymphopoiesis following severe radiation accidents-
      potential use for dose assessment.
AB  - A biomathematical model of lymphopoiesis is described and used to analyze the
      lymphocyte changes observed in the blood of exposed victims in radiation
      accidents. The coarse-grained architecture of cellular replication and production
      and implicit cellular regulation mechanisms used in this model make it
      straightforward to incorporate various radiation conditions. Model simulations
      with reported absorbed doses as inputs are shown to qualitatively and
      quantitatively describe a wide range of accidental data in vastly different
      scenarios. In addition, the absolute lymphocyte counts and the depletion rate
      constants calculated by this model show good correlation with two widely
      recognized empirical methods for early dose assessment. This demonstrates the
      potential to use the biophysical model as an alternative method for the
      assessment of radiation injury in the case of large-scale radiation disaster. The
      physiological assumptions underlying the model are also discussed, which may
      provide a putative mechanism for some biodosimetric tools that use the peripheral
      blood cell counts as markers of radiation impairment.

PMID- 22378205
TI  - Changes of radionuclides in the environment in Chiba, Japan, after the Fukushima
      nuclear power plant accident.
AB  - Damage to the Fukushima nuclear power plant caused by the 11 March 2011
      earthquake and tsunami off the northeast coast of Japan resulted in the release
      into the environment of radioactive material. Airborne radioactive material was
      detected in metropolitan areas near Tokyo, and increases in radiation dose rate
      were observed at many locations. In this study, repeated measurements with the in
      situ Ge system were performed in Chiba City, which is about 220 km south of
      Fukushima. Increases in radiation dose rate were recorded on 15, 16, and 21
      March, with a maximum of 0.5 MUGy h(-1). This level is clearly higher than
      natural background in Japan. Airborne (99)Mo, (99m)Tc, (129m)Te, (129)Te,
      (132)Te, (131)I, (132)I, (133)I, (133)Xe,(133m)Xe, (135)Xe, (134)Cs, (136)Cs,
      (137)Cs, and (140)La were detected. Environmental radioactive contamination in
      the metropolitan area occurred mainly on 21 March by rainfall. The initial rates
      of decrease in radiation dose rate generally reflected radiological decay
      according to their physical (radiological) half-lives. However, the in situ half
      lives of the long-lived radionuclides such as (134)Cs and (137)Cs reflected
      environmental dispersal rather than radiological decay.

PMID- 22378206
TI  - Cancer deaths and occupational exposure in a group of plutonium workers.
AB  - An exploratory epidemiological study was conducted for 319 deceased nuclear
      workers who had intakes of transuranic radionuclides and histories of employment
      during the time period from 1943 to 1995. The workers were employed at various
      facilities throughout the United States, including the Department of Energy
      defense facilities and uranium mining and milling sites. The majority of
      individuals were involved in documented radiological incidents during their
      careers. All had voluntarily agreed to donate their organs or whole body to the
      United States Transuranium and Uranium Registries. External and internal dose
      assessments were performed using occupational exposure histories and postmortem
      concentrations of transuranic radionuclides in critical organs. Statistical data
      analyses were performed to investigate the potential relationship between
      radiation exposure and causes of death within this population due to cancers of
      the lungs, liver, and all sites combined while controlling for the effects of
      other confounders. No association was found between radiation exposure and death
      due to cancer (alpha = 0.05). However, statistically significant associations
      were found between death due to any type of cancer and smoking (yes or no) (odds
      ratio = 5.41; 95% CI: 1.42 to 20.67) and rate of cigarette smoking (packs per
      day) (odds ratio = 2.70; 95% CI: 1.37 to 5.30).

PMID- 22378207
TI  - Monte Carlo assessment of the finger shallow dose from direct contact with a
      microcentrifuge tube containing common biotechnology isotopes in solution.
AB  - Eppendorf tubes often are used in biomedical research labs and contain
      radioactive tracers. Although the associated direct contact finger doses are
      typically small, it is suggested (and in line with the principle of ALARA) to
      handle these tubes from the cap of the tube. When containing radioactive
      material, handling a tube near the bottom conical section would unnecessarily
      increase the skin dose to the fingers. This investigation modeled a 2.0-mL
      Eppendorf tube containing various individual beta emitting isotopes commonly used
      in a biomedical research environment (i.e., (14)C, (3)H, (131)I, (32)P, and
      (35)S) to determine the skin dose when directly handling the tube at the cap end
      and when handling it at the bottom conical section. The primary goal of this
      paper is to assess how significantly this dose is altered by handling geometry.
      The skin dose to a single finger was calculated with Monte Carlo simulations
      using MCNP5 and determined at a depth of 0.007 cm(2) in water averaged over 10 cm
      as described in 10CFR20. Results show that the dose rate may vary by as much as a
      factor of 700 depending on handling geometry.

PMID- 22378208
TI  - Long term measurements of indoor radon equilibrium factor.
AB  - To provide detailed information for bronchial dose estimates, aerosol particle
      size distributions, and radon gas concentration, measurements were made in six
      residential homes and three laboratory rooms in different office buildings in the
      city of Ottawa. In the literature, most particle size distribution measurements
      are taken with samplers operating for a few days at most. In this study, the
      particle size samplers collected the samples from 77 to 162 d. The equilibrium
      factor determined from the long-term measurements ranged from 0.6 to almost 1
      with an average of 0.75. Even though radon concentrations were quite different
      between residential setting and office buildings, the average equilibrium factor
      was similar in the two different indoor environments. The results suggest that at
      least in some basements, if they were occupied, the radon dose would be about
      twice as high as normally estimated from the conventional F(eq) value of 0.4.

PMID- 22378209
TI  - Moving forward with safety culture.
AB  - Radiation safety and protection of people are shared goals of the Health Physics
      Society (HPS) and the U.S. Nuclear Regulatory Commission (NRC). A positive safety
      culture contributes to achieving radiation safety and protection of people, which
      are important to both the HPS and the NRC. Through unprecedented collaboration
      and engagement with diverse stakeholders, the NRC and the stakeholders developed
      a Safety Culture Policy Statement. The policy statement defines safety culture
      and describes the traits of a positive safety culture. Consideration of both
      safety and security issues and the interface of safety and security are
      underlying principles that support the policy. Examination of significant events,
      both within the nuclear industry and in society at large, illustrates how
      weaknesses in these traits can contribute to the occurrence and consequences of
      safety incidents, including serious injury and loss of life. With the policy
      statement in place, the NRC is moving forward with outreach and education about
      safety culture. Health physicists and other radiation safety specialists play an
      essential role in enhancing safety culture.

PMID- 22378210
TI  - Radiochemistry and measurement of 226Ra in human bone.

PMID- 22378216
TI  - Feasibility study on biweekly paclitaxel treatment as maintenance chemotherapy in
      advanced mullerian carcinoma.
AB  - AIM: To evaluate the feasibility of biweekly paclitaxel treatment as maintenance
      chemotherapy for patients with advanced mullerian carcinoma. METHODS: Thirty
      patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who
      underwent primary optimal surgery and standard 6 cycles of carboplatin/taxane
      based chemotherapy and exhibited a complete clinical response were entered in
      this study. Paclitaxel 80 mg/m(2) was administered biweekly for 12 cycles.
      Patients were evaluated monthly for treatment-related toxicity. RESULTS: Four
      patients, including 3 disease progressions and 1 bone marrow suppression, came
      off the protocol therapy. Twenty-six (86.7%) patients received complete
      treatment. Although the major toxicity was neutropenia, most of those patients
      (27/30, 90.0%) did not experience grade 3 or 4 neutropenia. Twenty-four (80.0%)
      patients showed persistent grade 1 neuropathy and the remaining 6 (20.0%) did not
      as a result of prior therapy. However, none experienced neuropathy progression
      during or after the protocol therapy. Most (17/22, 77.3%) of the completely
      treated patients experienced a regression of symptoms during and after therapy.
      CONCLUSION: Biweekly paclitaxel therapy is well tolerated by patients with
      advanced mullerian carcinoma and is therefore acceptable as a candidate for
      maintenance chemotherapy in these patients.

PMID- 22378217
TI  - CCM2 gene polymorphisms in Italian sporadic patients with cerebral cavernous
      malformation: a case-control study.
AB  - Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS
      characterized by abnormally enlarged capillary cavities that can occur
      sporadically or as a familial autosomal dominant condition with incomplete
      penetrance and variable clinical expression attributable to mutations in three
      different genes: CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Among our group
      of CCM Italian patients, we selected a cohort of sporadic cases negative for
      mutations in CCM genes. In this cohort, five variants in CCM2 gene were detected,
      which proved to be the known polymorphisms in intronic regions (IVS2-36A>G and
      IVS8 +119 C>T) and in coding sequence (c.157 G>A in exon 2, c.358 G>A in exon 4
      and c.915 G>A in exon 8). Therefore, we undertook a case-control study to
      investigate the possible association of these polymorphisms with sporadic CCMs.
      The five polymorphisms were identified in 91 CCM sporadic patients and in 100
      healthy controls by direct sequencing methods using lymphocyte DNA. Polymorphisms
      IVS2-36A>G and c.915 G>A showed statistically significant differences in
      frequencies between patients and controls [(chi2, 6.583; P<0.037); (chi2, 14.205;
      P<0.001)]. The prevalence of the wild-type genotype was significantly lower in
      the CCM group than in the control sample. Patients with the A/G and G/G genotypes
      (IVS2-36A>G) had a significant increase for CCM risk (OR, 3.08; 95% CI, 1.5-5.9
      and OR, 4.3; 95% CI, 1.4-22.6) and the same was observed for the polymorphism
      c.915 G> A (genotype G/A OR, 6.1; 95% CI, 3.0-12.6 and genotype A/A OR, 2.79). In
      addition, the polymorphisms c.358 G>A in exon 4 (chi2, 15.977; P<0.04) and c.915
      G>A in exon 8 (chi2, 18.109; P<0.02) were significantly associated with different
      types of symptoms. Haplotype analysis, performed only on polymorphisms c.358 G>A
      (p.Val120Ile), c.915 G>A (p.Thr305 Thr) and IVS2-36A>G, shows that haplotype GAG
      (+--) significantly increased among CCM sporadic patients compared to the control
      group. Significant differences between patients and controls were observed only
      for IVS2-36A>G and c.915 G>A polymorphisms indicating their possible association
      with sporadic CCMs and an increased risk of CCM. On the other hand, polymorphisms
      c.358 G>A and c.915 G>A were associated with a more benign course of the disease.
      These data were confirmed by the haplotype GAG (+--) frequencies.

PMID- 22378218
TI  - Multifunctional bioconjugation by Morita-Baylis-Hillman reaction in aqueous
      medium.
AB  - An efficient approach for modular assembly of multifunctional bioconjugates from
      oligosaccharides, peptides and proteins with fluorescent probes/affinity tags
      based on Morita-Baylis-Hillman (MBH) reaction in aqueous medium has been
      developed.

PMID- 22378219
TI  - Hydrocarbons and kidney damage: potential use of neutrophil gelatinase-associated
      lipocalin and sister chromatide exchange.
AB  - BACKGROUND: Millions of workers are exposed to polycyclic aromatic hydrocarbons
      (PAHs) and it is known that the kidney is a target for toxic chemicals. We have
      evaluated neutrophil gelatinase-associated lipocalin (NGAL) as a potential marker
      of tubular damage and have used it, with sister chromatid exchange (SCE)
      analysis, to evaluate carcinogenic risk in a group of workers from an oil
      refinery. METHODS: NGAL and SCE analysis were evaluated in 160 subjects. Exposed
      subjects were divided into three groups, according to levels of exposure to PAHs:
      40 highly exposed workmen (WM), 40 less exposed office workers (OW), and 40
      subjects (GE) living in Gela. The control group included 40 healthy subjects
      (HS). RESULTS: WM, OW and GE showed higher NGAL levels than HS. WM had higher
      levels of NGAL than the OW and GE groups; in ROC analysis, serum NGAL showed a
      good diagnostic profile (sensitivity 87.5%; specificity 100.0%), as did urinary
      NGAL (sensitivity 90.0%; specificity 92.5%). Moreover, regarding SCE analysis, WM
      showed higher values than HS. A direct correlation between SCE and serum NGAL was
      found in WM, the group most exposed to PAHs. CONCLUSION: The high values of NGAL
      are an expression of damage to the renal tubule determined by exposure to PAHs.
      Compared to the other groups studied, chromosomal aberrations - expressed as SCE 
      were increased in WM, the group most exposed to PAHs, indicating genotoxic
      damage. NGAL may also play a role in the process of carcinogenesis having a
      direct correlation with the number of SCEs.

PMID- 22378220
TI  - Perinatal outcomes following the ultrasound diagnosis of echogenic bowel: an
      Australian perspective.
AB  - INTRODUCTION: The aim of this study was to describe the association between fetal
      echogenic bowel (FEB) diagnosed during the second trimester and adverse perinatal
      outcomes in an Australian antenatal population. METHODS: A retrospective analysis
      of ultrasound scans was performed between March 1, 2004 and March 1, 2009 at The
      Royal Women's Hospital, Melbourne, Vic., Australia. Cases reported as having FEB
      on second trimester ultrasound were included. Medical records of each case were
      reviewed and information concerning additional investigations and perinatal
      outcomes were extracted. RESULTS: A total of 66 cases were identified in our
      database. Three patients (5%) were excluded from further analysis as they were
      lost to follow-up, leaving 63 (95%) cases in this series. Thirty-two fetuses
      (52%) underwent karyotyping via amniocentesis, 5 (16%) of which were found to
      have chromosomal defects. Maternal serology for cytomegalovirus (CMV) was
      performed in 49 (78%) cases. Investigations indicated a total of 5 women who had
      CMV infection during their pregnancy. Thirty-three pregnancies (53%) were tested
      for cystic fibrosis (CF) and 1 baby was confirmed to have CF postnatally. Among
      the 50 liveborn infants, 3 cases of fetal growth restriction were apparent.
      Overall, 42 of the 50 liveborn infants (84%) and 67% of the entire cohort of 63
      patients with a midtrimester diagnosis of FEB had a normal short-term neonatal
      outcome. CONCLUSION: This study reiterates the increased prevalence of
      aneuploidy, CMV, CF and fetal growth restriction in pregnancies complicated by
      the midtrimester sonographic finding of FEB. However, reassuringly, 67% of cases
      with ultrasound-detected echogenic bowel in the second trimester had a normal
      short-term neonatal outcome in this multiethnic Australian population.

PMID- 22378221
TI  - Aortic function: from the research laboratory to the clinic.
AB  - For many years, much of the pioneering research on aortic function was carried
      out by a small group of investigators frequently working away from the clinical
      environment in the research laboratory. The evaluation of aortic function using
      aortic pulse wave velocity, aortic distensibility, or other practical indices had
      yet to reach clinical threshold. It was necessary for the clinicians to take over
      and to apply these indices to the clinic. In this Odyssey, the work by the basic
      scientist was important to define the fundamental mechanisms of aortic function;
      however, it was the vision of the clinical investigator who recognized the
      importance of aortic function and introduced it into clinical practice. In the
      near future, the clinical investigator will introduce aortic function in daily
      clinical practice as the measurement of left ventricular function is used today.
      A close collaboration between the clinical and the basic investigator will be
      necessary in order to define the molecular mechanisms related to aortic wall
      synthesis and degradation of collagen and elastin. Application of these findings
      by the clinical investigator may help to delay or prevent aortic dysfunction
      related to aging or other conditions and diseases.

PMID- 22378222
TI  - Facilitated diffusion of VEGF165 through descemet's membrane with sucrose
      octasulfate.
AB  - Vascular endothelial growth factor A (VEGF-A) is a promoter of neovascularization
      and thus a popular therapeutic target for diseases involving excessive growth of
      blood vessels. In this study, we explored the potential of the disaccharide
      sucrose octasulfate (SOS) to alter VEGF165 diffusion through Descemet's membrane.
      Descemet's membranes were isolated from bovine eyes and used as a barrier between
      two chambers of a diffusion apparatus to measure VEGF transport. Diffusion
      studies revealed a dramatic increase in VEGF165 transport in the presence of SOS,
      with little diffusion of VEGF165 across the membrane over a 10-h time course in
      the absence of SOS. Diffusion studies with VEGF121, a non-heparin binding variant
      of VEGF, showed robust diffusion with or without SOS. To determine a possible
      mechanism, we measured the ability of SOS to inhibit VEGF interactions with
      extracellular matrix (ECM), using cell-free and cell surface binding assays.
      Binding studies showed SOS had no effect on VEGF165 binding to either heparin
      coated plates or endothelial cell surfaces at less than mg/ml concentrations. In
      contrast, we show that SOS inhibited VEGF165 binding to fibronectin in a dose
      dependent manner and dramatically accelerated the rate of release of VEGF165 from
      fibronectin. SOS also inhibited the binding of VEGF165 to fibronectin-rich ECM
      deposited by vascular smooth muscle cells. These results suggest that fibronectin
      rich extracellular matrices serve as barriers to VEGF165 diffusion by providing a
      network of binding sites that can trap and sequester the protein. Since the
      content of Descemet's membrane is typical of many basement membranes it is
      possible that they serve throughout the body as formidable barriers to VEGF165
      diffusion and tightly regulate its bioavailability and distribution within
      tissues.

PMID- 22378223
TI  - Long-term course of brain-derived neurotrophic factor serum levels in a patient
      treated with deep brain stimulation of the lateral habenula.
AB  - INTRODUCTION: According to the neurotrophin hypothesis, a brain-derived
      neurotrophic factor (BDNF) decrease has been postulated as a pivotal
      pathomechanism in affective disorder, and the treatment-associated increase in
      peripheral BDNF has been linked to therapeutic efficacy of antidepressant drugs
      and electroconvulsive therapy. However, in deep brain stimulation (DBS), a still
      experimental antidepressant treatment approach, this issue has not yet been
      investigated. METHODS: We examine the long-term course of serum BDNF levels in a
      64-year-old woman who is being treated with DBS of the lateral habenula for
      severe major depressive disorder. RESULTS: Our main findings are a significant
      increase in BDNF serum levels following DBS of the lateral habenula and an
      inverse U-shaped correlation of depression scores and BDNF levels. DISCUSSION:
      The data indicate that DBS, like other effective antidepressant treatments, may
      contribute to an increase in peripheral BDNF levels, which are thought to reflect
      central nervous DBS-induced neuroplastic changes. Moreover, our observations
      underscore the complex nature of disease-associated BDNF alterations. Their
      identification as either state or trait marker remains controversial and requires
      larger-scale longitudinal studies.

PMID- 22378224
TI  - A comparative validation of a child food frequency questionnaire using red blood
      cell membrane fatty acids.
AB  - BACKGROUND/OBJECTIVES: There are limited validated tools available for the
      assessment of dietary intake in pediatric populations. This report describes a
      comparative validation study of selected fatty acid intakes in children assessed
      by food frequency questionnaire (FFQ), compared with erythrocyte membrane fatty
      acids. SUBJECTS/METHODS: Overall, 46 overweight and 47 healthy-weight children
      aged 5-12 years (mean+/-SD, 9.1+/-1.3years, body mass index 20.5+/-4.0) were
      recruited; dietary fatty acid intakes assessed by parent report using a 135-item
      semi-quantitative FFQ, were compared with selected child erythrocyte membrane
      fatty acids assessed from fasting samples using gas chromatography. Spearman's
      rank correlation coefficients were calculated between fatty acid intake estimates
      (% of energy) and erythrocyte membrane concentrations (%mol/mol). RESULTS:
      Significant correlations were found between dietary and erythrocyte
      eicosapentanoic acid (EPA) concentration (r=0.24, P<0.05) with a statistical
      trend for total omega three (?n-3) fatty acids (r=0.22, P=0.06) and linoleic acid
      (r=0.32, P=0.07) in the healthy-weight children only. CONCLUSION: Parental report
      of selected child fatty acid intakes using an FFQ can be used to provide an
      estimate of child intake of EPA, but further work is required to quantify this
      relationship for other fatty acids and in other populations.

PMID- 22378225
TI  - Carbohydrate substitution for fat or protein and risk of type 2 diabetes in male
      smokers.
AB  - BACKGROUND/OBJECTIVES: We examined the associations between carbohydrate
      substitutions (total; low-, medium-, high-glycemic index (GI) carbohydrates) for
      fat or protein and risk of type 2 diabetes. SUBJECTS/METHODS: The cohort
      comprised 25,943 male smokers among whom 1098 diabetes cases were identified from
      a national register during a 12-year follow-up. Diet was assessed by a validated
      food frequency questionnaire. The relative risks (RR) and confidence intervals
      (CI) for diabetes were analyzed using Cox proportional hazard modeling, and
      multivariate nutrient density models were applied to examine the associations
      between substitutions of macronutrients and diabetes risk. RESULTS: The risk of
      diabetes was lower when fat or protein was replaced with an isoenergetic amount
      (2% of energy intake) of carbohydrates, the multivariate RRs were 0.96 (95% CI:
      0.94, 0.99) and 0.85 (95% CI: 0.80, 0.90), respectively. The lower risks were due
      to replacing saturated plus trans fatty acids, and meat, milk or plant protein
      with carbohydrates, respectively. Low-, medium- or high-GI carbohydrates did not
      associate with lower diabetes risk when replacing fat or fatty acids, except when
      total fat was replaced with medium-GI carbohydrates. Low-, medium- and high-GI
      carbohydrates had similar inverse associations with diabetes risk when they
      replaced total, meat or milk protein. CONCLUSION: Higher carbohydrate intake at
      the expense of fat, attributable to trans and saturated fatty acids, or protein
      was associated with decreased diabetes risk. Replacing fat or protein with lower
      GI carbohydrates was not more beneficial than replacing it with higher-GI
      carbohydrates.

PMID- 22378226
TI  - Effects of 25OHD concentrations on chances of pregnancy and pregnancy outcomes: a
      cohort study in healthy Danish women.
AB  - BACKGROUND/OBJECTIVES: Plasma 25-hydroxyvitamin D (P-25OHD) concentrations may
      affect pregnancy outcomes. To elucidate this further, we studied the effects of
      pre-conception P-25OHD concentrations on chances for pregnancy as well as the
      effects of P-25OHD during pregnancy on the risk of miscarriage, birth weight and
      length, Apgar score and head circumference. Moreover, we studied whether
      pregnancy and breastfeeding patterns affect maternal P-25OHD concentrations.
      SUBJECTS/METHODS: A total of 153 healthy Caucasian women with pregnancy plans
      were followed with measurements performed before pregnancy, at pregnancy weeks
      11+/-2, 22+/-1 and 35+/-2 as well as 15+/-7, 129+/-12 and 280+/-15 days
      postpartum. Furthermore, 75 non-pregnant, age-matched women were followed in
      parallel as controls. RESULTS: The 203 women were aged 29 (25-35) years. At
      baseline, median P-25OHD was 59 nmol/l. Of these women, 31% had P-25OHD <50
      nmol/l, whereas 12% had levels above 80 nmol/l. Within ~6 months after inclusion,
      63% conceived. P-25OHD was not associated with chances of conceiving or overall
      risk of miscarriage. However, women with a miscarriage in their second trimester
      (n=3) had lower P-25OHD concentrations at measurements performed in the first
      trimester compared with women without a miscarriage (P=0.03). P-25OHD before or
      during pregnancy was not associated with gestational length or infant parameters.
      Adjustments for possible confounders did not change the result. During pregnancy,
      P-25OHD changed significant over time, but similar changes occurred within the
      control group, indicating no effect of pregnancy per se (P=0.59). Overall, P
      25OHD did not differ according to length of breastfeeding at 2 weeks, and 4 and 9
      months postpartum, although women breastfeeding for >9 months had lower P-25OHD
      levels at the last visit compared with the controls. CONCLUSION: P-25OHD
      concentrations did not affect fertility or pregnancy outcomes, although low P
      25OHD may be associated with an increased risk of late miscarriage.

PMID- 22378227
TI  - Maternal nutrient intakes and levels of energy underreporting during early
      pregnancy.
AB  - BACKGROUND/OBJECTIVES: Pregnancy is a critical period in a woman's life where
      nutrition is of key importance for optimal pregnancy outcome. The aim of this
      study was to assess maternal nutrient intakes during early pregnancy and to
      examine potential levels of energy underreporting. SUBJECTS/METHODS: Three-day
      food diaries were collected from 260 healthy pregnant women sampled from the
      control arm of a large Irish pregnancy cohort at 14 weeks gestation (range 12-20
      weeks). RESULTS: Up to 45% of pregnant women may be underreporting daily energy
      intake (EI). Multiple logistic regression analysis found that having a body mass
      index (BMI) of >= 25 kg/m(2) compared with a BMI <25 kg/m(2) (odds ratio, 4.4;
      95% confidence interval, 2.5-7.7) was the main predictor of energy
      underreporting. Educational attainment is also an important predictor of energy
      underreporting. Women who underreport their EI tend to be less compliant with the
      current dietary recommendations for pregnancy. CONCLUSIONS: These data highlight
      the need for more education and public health interventions among pregnant women
      to achieve current dietary guidelines. In the analysis of dietary intakes,
      removal of extreme under reporters (Goldberg's ratio <0.9) may allow for more
      accurate assessment of nutritional intakes amongst pregnant women.

PMID- 22378228
TI  - Can birth weight predict later body composition in anorexia nervosa?
AB  - BACKGROUND/OBJECTIVES: The relationship between birth weight and body composition
      at later stages in life was not studied previously in anorexia nervosa (AN). The
      aim of the following brief report is to present results concerning the
      relationship between birth weight and later body composition specifically in AN,
      and to check if the programming of body composition from birth weight is still
      detected in severely emaciated AN patients. SUBJECTS/METHODS: One hundred and
      fifty-one female AN patients aged between 13 and 44 were recruited from 11
      inpatient treatment facilities in France. Birth weight, body weight and height
      were obtained. Body composition was measured using bioelectrical impedance. Birth
      weight was significantly correlated to lifetime maximum body mass index (BMI;
      r=0.211, P=0.009) and significantly correlated to fat-free mass index (r=0.190,
      P=0.027) but not to fat mass index (FMI). RESULTS: This report confirms that even
      in AN when patients are severely emaciated and where fat-free mass (FFM) and fat
      mass (FM) are low, a link between birth weight and FFM and BMI can still be
      identified, independently from age. CONCLUSION: Further studies are needed on
      larger samples exploring other factors, such as gender, puberty and ethnicity.

PMID- 22378229
TI  - The effect of current and lifetime alcohol consumption on overall and central
      obesity.
AB  - BACKGROUND/OBJECTIVE: To evaluate the association between current and lifetime
      alcohol consumption, and overall and central obesity in adults of an urban
      Portuguese population. SUBJECTS/METHODS: Participants were randomly selected from
      the non-institutionalized Porto inhabitants, aged >=18 years (EPIPorto Study:
      1999-2003). The study included 2366 participants for evaluating current alcohol
      consumption and overall obesity, and 2377 participants for central obesity. A
      trained interviewer applied a questionnaire and anthropometrics were measured.
      Data on alcohol intake were obtained by using a food frequency questionnaire.
      Overall obesity was considered when body mass index was >=30.0 kg/m(2), and
      central obesity when waist circumference (WC) was >=88 cm in women and >=102 cm
      in men. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated,
      separately by sex, using unconditional logistic regression models. RESULTS: After
      adjustment for age, education, smoking, energy intake and regular physical
      exercise, men who consumed >60g/day of alcohol were more frequently obese
      compared with non-drinkers (OR=2.26, 95% CI: 1.17-4.35). When considering
      lifetime alcohol consumption, the magnitude of the association was stronger in
      both women (OR=2.41, 95% CI: 1.28-4.56) and men (OR=4.22, 95% CI: 1.93-9.24). For
      central obesity, women consuming 15.1-30 g/day and >30 g/day had higher
      probability of being obese, considering both current and lifetime alcohol
      consumption. In men, the same positive associations were observed, which were
      particularly stronger between lifetime alcohol consumption and central obesity
      (>60g/day vs non-drinkers: OR=4.02, 95% CI: 1.80-8.98). CONCLUSION: Independently
      of social and behavioural features, current and lifetime alcohol consumption were
      positively associated with overall and central obesity, in both women and men.

PMID- 22378230
TI  - Bismuth 2,6-pyridinedicarboxylates: assembly of molecular units into coordination
      polymers, CO2 sorption and photoluminescence.
AB  - Six inorganic-organic bismuth 2,6-pyridinedicarboxylate (pdc) compounds, [Bi(2,6
      pdc)(3)].3(dma), 1, [Bi(2,6-pdc)(3)].3(dma).2(H(2)O), 2, [Bi(2,6
      pdc)(2)(dmf)].(dma), 3, Bi(2,6-pdc)(2,6-pdcme)(MeOH), 4, [LiBi(2,6
      pdc)(3)(H(2)O)].2(dma), 5, and Li(5)Bi(2,6-pdc)(4)(H(2)O)(2), 6 (where dma =
      dimethyl ammonium cation, dmf = dimethylformamide and 2,6-pdcme = 6-methyl
      oxycarbonyl pyridine 2-carboxylate) have been synthesized under solvothermal
      conditions and their structures determined by single crystal X-ray diffraction.
      Compounds 1-4 have molecular structures whereas compounds 5 and 6 form one- and
      three-dimensional frameworks, respectively. Compounds 1 and 2, both having
      similar monomeric bismuth coordination units, which are connected non-covalently
      into a (4,4)-connected square lattice by H-bonding interactions through dma
      cations. Compounds 3 and 4, both have a similar dimeric bismuth coordination
      unit. In 3, the dimers are connected into a one-dimensional chain by H-bonding
      interactions through dma cations. In the partially esterified and neutral 4,
      there was no such H-bonding interactions due to the absence of any dma cations.
      Compounds 5 and 6 have a similar monomeric bismuth coordination unit to that seen
      in 1 and 2. In 5, the monomers are connected through lithium cations into one
      dimensional chains, which further interact non-covalently by H-bonding
      interactions through dma cations. In the lithium-rich 6, the monomers are
      connected by the lithium cations and 2,6-pdc anions into a three dimensional
      structure with intramolecular H-bonding interactions involving the water
      molecules. The non-porous 5 and 6 exhibit a reasonable amount of H(2) and CO(2)
      sorptions, respectively. Tb(3+)- and Eu(3+)-doped and co-doped 4 and 5 emit
      characteristic sensitized green/red/yellow-orange luminescence.

PMID- 22378231
TI  - Molecular assembly directed by metal-aromatic interactions: control of the
      aggregation and photophysical properties of Zn-salen complexes by aromatic
      mercuration.
AB  - There is widespread interest in non-covalent bonding and weak interactions, such
      as electrostatic interactions, hydrogen bonding, solvophobic/hydrophobic
      interactions, metal-metal interactions, and pi-pi stacking, to tune the molecular
      assembly of planar pi-conjugated organic and inorganic molecules. Inspired by the
      roles of metal-aromatic interaction in biological systems, such as in ion
      channels and metalloproteins, herein, we report the first example of the use of
      Hg(2+) -aromatic interactions to selectively control the assembly and disassembly
      of zinc-salen complexes in aqueous media; moreover, this process exhibited
      significant "turn on" fluorescent properties. UV/Vis and fluorescence
      spectroscopic analysis of the titration of Hg(2+) ions versus complex ZnL(1)
      revealed that the higher binding affinity of Hg(2+) ions (compared to 13 other
      metal ions) was ascribed to specific interactions between the Hg(2+) ions and the
      phenyl rings of ZnL(1); this result was also confirmed by (1)H NMR spectroscopy
      and HRMS (ESI). Further evidence for this type of interaction was obtained from
      the reaction of small-molecule analogue L(1) with Hg(2+) ions, which demonstrates
      the proximity of the N-alkyl group to the aromatic protons during Hg(2+)-ion
      binding, which led to the consequential H/D exchange reaction with D(2) O. DFT
      modeling of such interactions between the Hg(2+) ions and the phenyl rings
      afforded calculated distances between the C and Hg atoms (2.29 A) that were
      indicative of C-Hg bond-formation, under the direction of the N atom of the
      morpholine ring. The unusual coordination of Hg(2+) ions to the phenyl ring of
      the metallosalen complexes not only strengthened the binding ability but also
      increased the steric effect to promote the disassembly of ZnL(1) in aqueous
      media.

PMID- 22378232
TI  - Effects of silencing cyclooxygenase-2 expression via RNA interference on the
      tumorigenicity of the SMMC-7721 human hepatocarcinoma cell line.
AB  - We constructed a vector carrying a shRNA sequence against cyclooxygenase-2 (COX
      2) that was subsequently transfected into the human hepatocarcinoma cell line
      SMMC-7721. Furthermore, we established a COX-2-deficient stable cell line and a
      model of tumor-shRNA transplantation in nude mice. Negative shRNA was used as the
      control. The tumor volume in the experimental group was smaller compared to that
      in the control group. Hematoxylin and eosin staining indicated that the cells in
      the experimental group differentiated better than those in the control group. The
      COX-2 mRNA level in the tumor tissues injected with SMMC-7721/COX-2i was markedly
      downregulated compared to that in the tumor tissues injected with SMMC
      7721/negative shRNA. The inhibition rate reached 68.6%. Immunohistological study
      showed a significantly strong COX-2 expression in the control group tumor cells,
      whereas the experimental group exhibited moderate expression, indicating the
      inhibition of COX-2 expression after transfection of cells with shRNA against COX
      2. Western blot analysis further proved the inhibition of COX-2 expression. In
      conclusion, RNAi-mediated regulation of COX-2 expression could efficiently
      inhibit liver-transplanted tumor growth in BALB/c nude mice.

PMID- 22378233
TI  - Liver proteome changes induced by a short-term high-fat sucrose diet in wistar
      rats.
AB  - BACKGROUND/AIMS: The aim of this study was to gain insight into those proteins
      that might be involved in the early stages of liver fat accumulation as a
      consequence of a different fat versus simple sugar dietary intake. METHODS: Forty
      five male Wistar rats were randomly distributed into four dietary groups: a
      starch-rich control diet (CD; n = 10), a high-fat diet (n = 12), a high-sucrose
      diet (n = 11), and a high-fat sucrose diet (HFSD; n = 12) for 5 weeks. A
      comparative analysis by 2D-DIGE and LC-ESI-MS/MS was performed to characterize
      the liver protein expression profiles due to the three obesogenic diets. RESULTS:
      Ten out of 17 proteins whose expression levels were altered by >1.25-fold were
      identified. Four proteins (Hspa8, Hspa9, Ca3, and Cat) were differentially
      expressed after the HFSD period compared to CD. The heat shock proteins (Hspa8
      and Hspa9) resulted significantly downregulated in liver from rats fed HFSD
      versus CD (p < 0.05). The results were confirmed by Western blot. CONCLUSIONS:
      This descriptive study might be useful for further studies aiming at
      understanding the mechanisms by which diets rich in both fat and sugar affect the
      initiation of hepatic steatosis.

PMID- 22378234
TI  - Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid
      cells from normal donors and beta-thalassemia patients.
AB  - Thalassemia and sickle-cell anemia (SCA) present a major public health problem in
      countries where the number of carriers and affected individuals is high. As a
      result of the abnormalities in hemoglobin production, cells of thalassemia and
      SCA patients exhibit oxidative stress, which ultimately is responsible for the
      chronic anemia observed. Therefore, identification of compounds exhibiting both
      antioxidant and hemoglobin-inducing activities is highly needed. Our results
      demonstrate resveratrol to be such a compound. This was shown both in the human
      K562 cell line, as well as in erythroid precursors derived from normal donors and
      beta-thalassemia patients. Resveratrol was shown to exhibit antioxidant activity
      and to stimulate the expression of the gamma-globin genes and the accumulation of
      fetal hemoglobin (HbF). To the best of our knowledge, this is the first report
      pointing to such a double effect of resveratrol. Since this natural product is
      already marketed as an antioxidant, future investigations should concentrate on
      demonstrating its potential to augment HbF production in experimental animal
      models (e.g., thalassemia and SCA mice) as well as in patients. We believe that
      the potential of clinical use of resveratrol as an antioxidant and HbF stimulator
      may offer a simple and inexpensive treatment to patients.

PMID- 22378235
TI  - Long-term follow-up of hemodynamic responders to pharmacological therapy after
      variceal bleeding.
AB  - Although it is assumed that hemodynamic responders to pharmacological therapy
      after a variceal hemorrhage are adequately protected from rebleeding, there is no
      evidence that either this response or its protective effect extend beyond the
      usual 2-year follow-up featured in available studies. We aimed to assess the
      maintenance of hemodynamic response and its impact on outcomes in a large cohort
      of hemodynamic responders during a long follow-up. One hundred three patients
      with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were
      prospectively evaluated. The hepatic venous pressure gradient (HVPG) was
      determined 5 days after the bleeding and repeated 5-7 days after maximal
      tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG <= 12 mm Hg
      or >= 20% decrease from baseline) were maintained on drugs and followed up with
      annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders.
      The median follow-up was 48 months (range, 2-108 months). Long-term HVPG
      evaluations could not be performed in eight patients (four deaths, two
      rebleedings, two follow-ups <1 year). Among the remaining 40 patients,
      hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were
      no baseline differences between the two subgroups. However, 100% of alcoholic
      patients who remained abstinent maintained long-term response, compared with 36%
      of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients
      with loss of hemodynamic response rebled more during follow-up and showed a
      higher incidence of death or liver transplantation. CONCLUSIONS: After variceal
      bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly
      restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of
      this long-term response carries worse clinical outcomes.

PMID- 22378239
TI  - Successful treatment of severe fetal chylothorax resistant to repeated
      pleuroamniotic shunting by OK-432 pleurodesis.
AB  - We report the first case of successful fetal pleurodesis with OK-432 for
      recurrent severe fetal primary chylothorax after failing repeated pleuroamniotic
      shunting. Shunting and pleurodesis could be complementary to each other in the
      treatment of fetal chylothorax.

PMID- 22378240
TI  - Multi-class HingeBoost. Method and application to the classification of cancer
      types using gene expression data.
AB  - BACKGROUND: Multi-class molecular cancer classification has great potential
      clinical implications. Such applications require statistical methods to
      accurately classify cancer types with a small subset of genes from thousands of
      genes in the data. OBJECTIVES: This paper presents a new functional gradient
      descent boosting algorithm that directly extends the HingeBoost algorithm from
      the binary case to the multi-class case without reducing the original problem to
      multiple binary problems. METHODS: Minimizing a multi-class hinge loss with
      boosting technique, the proposed HingeBoost has good theoretical properties by
      implementing the Bayes decision rule and providing a unifying framework with
      either equal or unequal misclassification costs. Furthermore, we propose Twin
      HingeBoost which has better feature selection behavior than HingeBoost by
      reducing the number of ineffective covariates. Simulated data, benchmark data and
      two cancer gene expression data sets are utilized to evaluate the performance of
      the proposed approach. RESULTS: Simulations and the benchmark data showed that
      the multi-class HingeBoost generated accurate predictions when compared with the
      alternative methods, especially with high-dimensional covariates. The multi-class
      HingeBoost also produced more accurate prediction or comparable prediction in two
      cancer classification problems using gene expression data. CONCLUSIONS: This work
      has shown that the HingeBoost provides a powerful tool for multi-classification
      problems. In many applications, the classification accuracy and feature selection
      behavior can be further improved when using Twin HingeBoost.

PMID- 22378241
TI  - Using health rights to improve programme design: a Papua New Guinea case study.
AB  - The non-state sector is becoming increasingly influential in funding and
      implementing global health programmes. However, their disease-specific focus and
      vertical interventions have led to criticism that these programmes can be
      unsustainable and unable to achieve long-term goals. This paper demonstrates that
      health rights can inform programme design to guide the design of appropriate and
      sustainable aid-funded health programmes. It draws on UN General Comment 14,
      which clarified the right to health duties of states and their international
      partners, and which determined that 'core obligations' in health must become
      progressively available, accessible, acceptable and of good quality. A rights
      based tool assessed the design of activities proposed for Papua New Guinea by a
      consortium of Australian non-government organisations. The tool revealed that
      none of the 36 indicators was addressed in full. Five of the 12 indicators
      pertaining to availability were addressed partially, as were three of 10 relating
      to accessibility and one of six concerning human rights concepts. As shown by the
      case study, failure to address the indicators in this tool will result in
      simplistic programme designs that can win political or financial support, but
      will fail to respect health rights or deliver a quality health service,
      available, accessible and acceptable to all.

PMID- 22378242
TI  - Differential contribution of the guanylyl cyclase-cyclic GMP-protein kinase G
      pathway to the proliferation of neural stem cells stimulated by nitric oxide.
AB  - Nitric oxide (NO) is an important inflammatory mediator involved in the initial
      boost in the proliferation of neural stem cells following brain injury. However,
      the mechanisms underlying the proliferative effect of NO are still unclear. The
      aim of this work was to investigate whether cyclic GMP (cGMP) and the cGMP
      dependent kinase (PKG) are involved in the proliferative effect triggered by NO
      in neural stem cells. For this purpose, cultures of neural stem cells isolated
      from the mouse subventricular zone (SVZ) were used. We observed that long-term
      exposure to the NO donor (24 h), NOC-18, increased the proliferation of SVZ cells
      in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented
      cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also
      increased cell proliferation. Interestingly, shorter exposures to NO (6 h)
      increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase
      pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative
      effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative
      effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages
      by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell
      proliferation by targeting these two pathways in a biphasic manner.

PMID- 22378243
TI  - Stepwise synthesis of sandwich-structured composite zeolite membranes with
      enhanced separation selectivity.
AB  - Sandwich-structured composite zeolite membranes with enhanced hydrogen
      selectivity were prepared on porous alpha-Al(2)O(3) supports by using 3
      aminopropyltriethoxysilane as an interlayer.

PMID- 22378244
TI  - Cardiogenic shock and awe.

PMID- 22378245
TI  - Synthesis and characterization of a singlet delocalized 2,4-diimino-1,3
      disilacyclobutanediyl and a silylenylsilaimine.
AB  - The synthesis and characterization of a singlet delocalized 2,4-diimino-1,3
      disilacyclobutanediyl, [LSi(MU-CNAr)(2)SiL] (2, L: PhC(NtBu)(2), Ar: 2,6-iPr(2)
      C(6) H(3)), and a silylenylsilaimine, [LSi(=NAr)-SiL] (3), are described. The
      reaction of three equivalents of the disilylene [LSi-SiL] (1) with two
      equivalents of ArN=C=NAr in toluene at room temperature for 12 h afforded [LSi(MU
      CNAr)(2)SiL] (2) and [LSi(=NAr)-SiL] (3) in a ratio of 1:2. Compounds 2 and 3
      have been characterized by NMR spectroscopy and X-ray crystallography. Compound 2
      was also investigated by theoretical studies. The results show that compound 2
      possesses singlet biradicaloid character with an extensive electronic
      delocalization throughout the Si(2)C(2) four-membered ring and exocyclic C=N
      bonds. Compound 3 is the first example of a silylenylsilaimine, which contains a
      low-valent silicon center and a silaimine substituent. A mechanism for the
      formation of 2 and 3 is also proposed.

PMID- 22378247
TI  - Expression of Cav-1 in tumour cells, rather than in stromal tissue, may promote
      cervical squamous cell carcinoma proliferation, and correlates with high-risk HPV
      infection.
AB  - Altered expression of caveolin-1 (Cav-1) is observed in various types of cancers.
      However, little research has been reported regarding the correlation between the
      expression of Cav-1 and cervical cancer. Here, we investigated the clinical
      significance of Cav-1 expression using quantum dot (QD)-based immunofluorescence
      staining in cervical cancer and its correlation with high-risk human papilloma
      virus (HPV) infection detected by chromogenic in situ hybridization. Our results
      showed that the positive rates of Cav-1 protein in normal cervical mucosa, CIN,
      cervical adenocarcinoma and SCC were: 0, 33, 19 and 55%, respectively. The
      differences in Cav-1 protein expression in cervical SCC compared to the other
      three groups were all statistically significant. Absence of stromal Cav-1 protein
      in 58 cases of cervical SCC was 67%. The positive rates of the Cav-1 protein in
      tumour and stromal cells of cervical SCC were not correlated with
      clinicopathological parameters. In the cervical SCC tissues, Cav-1 expression in
      tumour cells was not associated with stromal Cav-1 expression, but a positive
      correlation existed with the PCNA protein and high-risk of HPV infection. The
      results presented here suggest that expression of Cav-1 in the tumour cells,
      rather than in the stromal tissue surrounding the tumour, may promote cervical
      SCC cell proliferation, and correlates with high-risk HPV infection.

PMID- 22378246
TI  - Renal adaptation to gentamicin-induced mineral loss.
AB  - BACKGROUND: Gentamicin, a well-known nephrotoxic drug, affects calcium and
      magnesium homeostasis. Although gentamicin induces urinary calcium and magnesium
      wasting immediately, it rarely causes significant hypocalcemia or hypomagnesemia
      clinically. METHODS: We conducted an animal study to investigate the renal
      adaptation in calcium and magnesium handling after gentamicin treatment and
      effects on the expression of calcium and magnesium transport molecules in distal
      tubule. Gentamicin (40 mg/kg) was injected daily in male Sprague-Dawley rats (220
      250 g) for up to 7 days. RESULTS: This treatment did not affect serum creatinine,
      calcium, or magnesium levels. Gentamicin induced significant hypercalciuria (14
      fold) and hypermagnesiuria (10-fold) in 6 h, which was associated with
      upregulation of TRPV5 (175 +/- 3%), TRPV6 (170 +/- 4%), TRPM6 (156 +/- 4%) and
      calbindin-D28k (174 +/- 3%; all p < 0.05 vs. control). This gene upregulation was
      maintained with daily injection of gentamicin for 7 days. The gentamicin-induced
      urinary calcium loss was reduced by 80% at days 3 and 7, while magnesium loss was
      reduced by 52 and 57% at days 3 and 7, respectively. On the other hand, urinary
      loss of potassium became worse on day 7 (2-fold), and phosphorus loss worse from
      day 3 to day 7 (3-fold). CONCLUSION: There is a rapid adaptation to gentamicin
      induced hypercalciuria and hypermagnesiuria. The upregulation of distal tubule
      transport molecules, TRPV5, TRPV6, TRPM6 and calbindin-D28k occurs within 6 h of
      gentamicin treatment. This renal adaptation prevents further mineral loss due to
      gentamicin treatment.

PMID- 22378248
TI  - Recapitulation of mesenchymal condensation enhances in vitro chondrogenesis of
      human mesenchymal stem cells.
AB  - Mesenchymal condensation is a critical transitional stage that precedes cartilage
      formation during embryonic development. We hypothesized that "priming" hMSCs to
      recapitulate mesenchymal condensation events prior to inducing differentiation
      would enhance their subsequent chondrogenic properties. Our prior studies have
      suggested that exposing hMSCs to hypoxia (2% O(2)) induces condensation-like
      effects. We therefore assessed the effect of preconditioning for different time
      periods on the expression of condensation specific genes by growing hMSCs in
      expansion medium under different normoxic (20% O(2)) and hypoxic conditions for
      up to 2 weeks, and subsequently induced chondrogenesis of preconditioned hMSCs.
      The total cultivation time for each group was 4 weeks and the chondrogenic
      properties were assessed using gene expression, biochemical analysis, and
      histological staining. Our results demonstrated the benefits of preconditioning
      were both time- and oxygen-dependent. Condensation specific genes, SOX-9 and
      NCAM, were significantly up-regulated in hypoxic conditions at the end of 1 week.
      COL X and MMP13 expression was also lower than the normoxic samples at this time
      point. However, this group did not exhibit more efficient chondrogenesis after 4
      weeks. Instead, hMSCs preconditioned for 1 week and subsequently differentiated,
      both under 20% O(2), resulted in the most efficient chondrogenesis.
      Interestingly, while hypoxia appears to positively enhance expression of
      chondrogenic genes, this did not produce an enhanced matrix accumulation. The
      results of this study emphasize the significance of considering the timing of
      specific cues in developing protocols for stem cell-based therapies and
      underscore the complexity in regulating stem cell differentiation and tissue
      formation.

PMID- 22378249
TI  - Upper and lower extremity muscle strength levels associated with an exercise
      capacity of 5 metabolic equivalents in male patients with heart failure.
AB  - PURPOSE: Exercise capacity of fewer than 5 metabolic equivalents (METs) has been
      associated with high risk of death and poor physical functioning in male patients
      with heart failure (HF). Therefore, we aimed to determine upper and lower
      extremity muscle strength levels required to attain an exercise capacity of 5 or
      more METs in male outpatients with HF. METHODS: We enrolled 148 male HF patients
      (age 60.1 +/- 1.0 years). Peak oxygen uptake (peak (Equation is included in full
      text article.)o2) was assessed by cardiopulmonary exercise testing (CPX). After
      CPX, we further divided the patients into groups according to exercise capacity:
      5 or more METs (group A, n = 85) and fewer than 5 METs (group B, n = 63).
      Handgrip strength and knee extensor and flexor muscle strengths were assessed as
      indices of upper and lower extremity muscle strength, respectively. Receiver
      operating characteristic curves were used to select cutoff values for upper and
      lower extremity muscle strength resulting in an exercise capacity of 5 or more
      METs in these patients. RESULTS: Exercise capacity of 5 or more METs in male HF
      patients was equivalent to approximately 35.2 kgf of handgrip strength and 1.70
      Nm/kg of knee extensor and 0.90 Nm/kg of knee flexor muscle strengths.
      CONCLUSIONS: These upper and lower extremity muscle strength values may be useful
      target goals for improvement of exercise capacity, risk management, and
      activities of daily living in male HF patients.

PMID- 22378251
TI  - Short- and long-term major adverse cardiac events in patients undergoing
      percutaneous coronary intervention with stenting for acute myocardial infarction
      complicated by cardiogenic shock.
AB  - OBJECTIVES: To determine the risk of short- and long-term mortality and major
      adverse cardiac events (MACE) in acute myocardial infarction (AMI) patients
      complicated by cardiogenic shock (CS) in the contemporary practice of primary
      percutaneous coronary intervention with stenting. METHODS: Of the 1,755
      consecutive AMI patients undergoing percutaneous coronary intervention with
      stenting enrolled, 103 had CS at admission. Primary endpoints were early
      mortality (within 30 days after the index event) and late mortality (from day 31
      up to 4 years). Secondary endpoints included MACE [all-cause death, myocardial
      infarction or target vessel revascularization (TVR)], myocardial infarction, TVR
      and stent thrombosis. RESULTS: Thirty-day mortality was higher among CS patients,
      and CS was a strong independent predictor of a higher risk of early death
      (adjusted HR 3.64, 95% CI 2.44-5.44). The late mortality rate was significantly
      higher in CS patients, and CS was also a predictor of higher risk of death at a 4
      year follow-up (adjusted HR 1.95, 95% CI 1.11-3.45). Recurrent AMI, TVR and stent
      thrombosis rates were similar among patients with and without CS. CONCLUSION: CS
      complicating AMI is still a severe clinical event, mainly with regard to a
      significant higher risk of early mortality, but also associated with a worse
      prognosis in 30-day survivors.

PMID- 22378252
TI  - Mesostructured chitosan-silica hybrid as a biodegradable carrier for a pH
      responsive drug delivery system.
AB  - A biodegradable mesoporous chitosan-silica hybrid has been synthesized by self
      assembly of non-toxic F127 Pluronic non-ionic surfactant, biodegradable chitosan
      and silica source through a real liquid-crystal templating route. On the basis of
      these biodegradable hybrids, we developed a facile one-pot pH-responsive drug
      delivery system relying on the coordinate bonding of a "host-metal-guest"
      architecture. Here, the "host", "metal" and "guest" represent amino groups of
      chitosan units, metal ions and drug molecules, respectively. Here, daunorubicin
      (DNR) was chosen as a typical anti-cancer drug molecule, the release of which can
      be achieved through the cleavage of the coordination bonds that are sensitive to
      variations in external pH at weak acidic conditions. The successful release of
      DNR has been observed at pH 5-6, while negligible release has been observed under
      physiological conditions. The existence of chitosan in the mesoporous silica
      enhanced both the biodegradability and the strength of the "host-metal-guest"
      coordination bond.

PMID- 22378253
TI  - Regularization for generalized additive mixed models by likelihood-based
      boosting.
AB  - OBJECTIVE: With the emergence of semi- and nonparametric regression the
      generalized linear mixed model has been extended to account for additive
      predictors. However, available fitting methods fail in high dimensional settings
      where many explanatory variables are present. We extend the concept of boosting
      to generalized additive mixed models and present an appropriate algorithm that
      uses two different approaches for the fitting procedure of the variance
      components of the random effects. METHODS: The main tool developed is likelihood
      based componentwise boosting that enforces variable selection in generalized
      additive mixed models. In contrast to common procedures they can be used in high
      dimensional settings where many covariates are available and the form of the
      influence is unknown. The complexity of the resulting estimators is determined by
      information criteria. The performance of the methods is investigated in
      simulation studies for binary and Poisson responses with comparisons to
      alternative approaches and it is applied to clinical real world data. RESULTS:
      Simulations show that the proposed methods are considerably more stable and more
      accurate in estimating the regression function than the conventional approach,
      especially when a large number of predictors is available. The methods also
      produce reasonable results in applications to real data sets, which is
      illustrated by the Multicenter AIDS Cohort Study. CONCLUSIONS: The boosting
      algorithm allows to extract relevant predictors in generalized additive mixed
      models. It works in high-dimensional settings and is very stable.

PMID- 22378254
TI  - Advancing the development of tuberculosis therapy.
AB  - Although the development of novel drugs and combination regimens for tuberculosis
      has accelerated in recent years, the pipeline remains thin and major challenges
      remain to be addressed in efficiently evaluating newer drugs to improve treatment
      outcomes, shorten duration of therapy and tackle drug resistance.

PMID- 22378255
TI  - Protein-protein interaction inhibitors get into the groove.

PMID- 22378257
TI  - Trial watch: integrin antagonist shows promise in MS.

PMID- 22378258
TI  - Market watch: industry perspectives on personalized medicine.

PMID- 22378260
TI  - An audience with Guido Rasi. Interview by Asher Mullard.

PMID- 22378261
TI  - Maximizing the value of diagnostics in Alzheimer's disease drug development.

PMID- 22378262
TI  - Tafamidis.
AB  - In November 2011, tafamidis (Vyndaqel; Pfizer), a small molecule that inhibits
      the dissociation of transthyretin tetramers, was granted marketing authorization
      by the European Commission for the treatment of transthyretin amyloidosis in
      adult patients with stage 1 symptomatic polyneuropathy to delay peripheral
      neurological impairment.

PMID- 22378263
TI  - Metabolomics: Gaining insight into pain.

PMID- 22378267
TI  - Anticancer drugs: Targeting menin.

PMID- 22378269
TI  - Diagnosing the decline in pharmaceutical R&D efficiency.
AB  - The past 60 years have seen huge advances in many of the scientific,
      technological and managerial factors that should tend to raise the efficiency of
      commercial drug research and development (RD). Yet the number of new drugs
      approved per billion US dollars spent on RD has halved roughly every 9 years
      since 1950, falling around 80-fold in inflation-adjusted terms. There have been
      many proposed solutions to the problem of declining RD efficiency. However, their
      apparent lack of impact so far and the contrast between improving inputs and
      declining output in terms of the number of new drugs make it sensible to ask
      whether the underlying problems have been correctly diagnosed. Here, we discuss
      four factors that we consider to be primary causes, which we call the 'better
      than the Beatles' problem; the 'cautious regulator' problem; the 'throw money at
      it' tendency; and the 'basic research-brute force' bias. Our aim is to provoke a
      more systematic analysis of the causes of the decline in RD efficiency.

PMID- 22378275
TI  - Estrogen receptor beta transcript variants associate with oncogene expression in
      endometrial cancer.
AB  - The human ESR2 gene codes for estrogen receptor beta1 and for multiple splice
      variants, which are suggested to exert distinct functions in the cellular
      estrogen response. Given that the function of ERbeta in endometrial cancer
      remains unclear, we examined the expression of ERbeta1, ERbeta2 and various
      further ERbeta transcript variants and their association with selected cancer
      related genes in 74 human endometrium samples and endometrial cancer specimens by
      means of RT-qPCR. Additionally, we knocked down ERbeta expression in HEC-1A
      endometrial adenocarcinoma cells by means of siRNA transfection. Expression of
      four ERbeta transcript variants was significantly elevated in cancer tissue or in
      G3 tumors compared to postmenopausal endometrium. Expression of ERbeta1, ERbeta2,
      ERbeta5 and five further variants was associated with the oncogenes MYBL2 or HER2
      in endometrial cancer. In addition, siRNA-triggered knockdown of ERbeta
      expression led to a significant decline of MYBL2 mRNA and protein levels in
      endometrial cancer cells. Our observation of increased ERbeta transcript levels
      in cancer tissue and particularly their correlation with the expression of
      oncogenes, as well as the results of our knockdown studies, suggest a role of
      ERbeta in endometrial carcinogenesis.

PMID- 22378276
TI  - Reduced adenosine release from the aged mammalian heart.
AB  - Adenosine (ADO) released in the heart results in enhanced coronary blood flow and
      reduced catecholamine release and myocardial responsiveness to adrenergic
      stimulation (anti-adrenergic action). ADO release from the adrenergic-stimulated
      aged heart is less than that from the young adult heart. Because adrenergic
      signaling in the aged heart is impaired, this study was conducted to determine if
      reduced ADO release from the aged heart results from this reduced adrenergic
      responsiveness. Hearts of 3-4 months (young adult) and 21-22 months (aged)
      Fischer-344 rats were perfused with ADO deamination and re-phosphorylation
      inhibited. Coronary effluent ADO levels were determined. Cellular-free ADO levels
      with and without sodium acetate (NaAc)-induced mitochondrial AMP synthesis were
      assessed using formed S-adenosylhomocysteine (SAH) in L-homocysteine thiolactone
      (L-HC)-treated hearts. The activities of SAH-hydrolase were determined. Aged
      heart ADO release was 61% less than from young hearts. NaAc augmented young heart
      ADO release by 104%, while that of aged hearts remained unchanged. SAH synthesis
      was 51% and 56% lower in the aged heart in the absence and presence of NaAc,
      respectively, despite an 89% greater SAH hydrolase activity found in the aged
      hearts. Since synthesized AMP may be diverted to IMP and ultimately inosine by
      AMP deaminase, inosine release was determined. Aged heart inosine levels in the
      absence and presence of NaAc were 74% and 59% less than for the young hearts. It
      is concluded that a reduced mitochondrial AMP synthesis is in part responsible
      for the attenuation in ADO release from the adrenergic-stimulated aged heart.

PMID- 22378277
TI  - Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole
      exome analysis.
AB  - We studied and validated facioscapulohumeral muscular dystrophy (FSHD) samples
      from patients without a D4Z4 contraction (FSHD2 or 'phenotypic FSHD'). For this,
      we developed non-radioactive protocols to test D4Z4 allele constitution and DNA
      methylation, and applied these to samples from the Coriell Institute Cell
      Repository. The D4Z4 sizing showed two related subjects to have classic
      chromosome 4 contraction-dependent FSHD1. A third sample (GM17726) did not have a
      short chromosome 4 fragment, and had been assigned as non-4q FSHD (FSHD2). We
      tested D4Z4 haplotype and methylation for this individual but found both to be
      inconsistent with this diagnosis. Using exome sequencing, we identified two known
      pathogenic mutations in CAPN3 (Arg490Gln and Thr184Argfs(*)36), indicating a case
      of LGMD2A rather than FSHD. Our study shows how a wrong diagnosis can easily be
      corrected by whole-exome sequencing by constraining the variant analysis to
      candidate genes after the data have been generated. This new way of 'diagnosis by
      sequencing' is likely to become common place in genetic diagnostic laboratories.
      We also publish a digoxigenin-labeled Southern protocol to test D4Z4 methylation.
      Our data supports hypomethylation as a good epigenetic predictor for FSHD2. The
      non-radioactive protocol will help to make this assay more accessible to clinical
      diagnostic laboratories and the wider FSHD research community.

PMID- 22378270
TI  - Inflammatory bone loss: pathogenesis and therapeutic intervention.
AB  - Bone is a tissue undergoing continuous building and degradation. This remodelling
      is a tightly regulated process that can be disturbed by many factors,
      particularly hormonal changes. Chronic inflammation can also perturb bone
      metabolism and promote increased bone loss. Inflammatory diseases can arise all
      over the body, including in the musculoskeletal system (for example, rheumatoid
      arthritis), the intestine (for example, inflammatory bowel disease), the oral
      cavity (for example, periodontitis) and the lung (for example, cystic fibrosis).
      Wherever inflammatory diseases occur, systemic effects on bone will ensue, as
      well as increased fracture risk. Here, we discuss the cellular and signalling
      pathways underlying, and strategies for therapeutically interfering with, the
      inflammatory loss of bone.

PMID- 22378278
TI  - Clinical utility gene card for: biotinidase deficiency.

PMID- 22378279
TI  - High prevalence of genetic variants previously associated with LQT syndrome in
      new exome data.
AB  - To date, hundreds of variants in 13 genes have been associated with long QT
      syndrome (LQTS). The prevalence of LQTS is estimated to be between 1:2000 and
      1:5000. The knowledge of genetic variation in the general population has until
      recently been limited, but newly published data from NHLBI GO Exome Sequencing
      Project (ESP) has provided important knowledge on this topic. We aimed to
      investigate the prevalence of previously LQTS-associated variants in ESP (5400
      individuals), in order to identify possible false-positive LQTS variants. With
      this aim, we performed a search for previously published LQTS-associated variants
      in ESP. In addition, a PolyPhen-2 prediction was conducted, and the four most
      prevalent LQTS-associated variants with significant functional effects present in
      ESP were genotyped in a second control population. We identified 33 missense
      variants previously associated with LQTS in ESP. These 33 variants affected 173
      alleles and this corresponded to a LQTS prevalence of 1:31 in the ESP population.
      PolyPhen-2 predicted 30% of the 33 variants present in ESP to be benign compared
      with 13% among LQTS-associated variants not present in ESP (P=0.019). Genotyping
      of the four variants KCNH2 P347S; SCN5A: S216L, V1951L; and CAV3 T78M in the
      control population (n=704) revealed prevalences comparable to those of ESP. Thus,
      we identified a much higher prevalence of previously LQTS-associated variants
      than expected in exome data from population studies. Great caution regarding the
      possible disease causation of some of these variants has to be taken, especially
      when used for risk stratification in family members.

PMID- 22378280
TI  - Dissecting the genetic make-up of North-East Sardinia using a large set of
      haploid and autosomal markers.
AB  - Sardinia has been used for genetic studies because of its historical isolation,
      genetic homogeneity and increased prevalence of certain rare diseases.
      Controversy remains concerning the genetic substructure and the extent of genetic
      homogeneity, which has implications for the design of genome-wide association
      studies (GWAS). We revisited this issue by examining the genetic make-up of a
      sample from North-East Sardinia using a dense set of autosomal, Y chromosome and
      mitochondrial markers to assess the potential of the sample for GWAS and fine
      mapping studies. We genotyped individuals for 500K single-nucleotide
      polymorphisms, Y chromosome markers and sequenced the mitochondrial hypervariable
      (HVI-HVII) regions. We identified major haplogroups and compared these with other
      populations. We estimated linkage disequilibrium (LD) and haplotype diversity
      across autosomal markers, and compared these with other populations. Our results
      show that within Sardinia there is no major population substructure and thus it
      can be considered a genetically homogenous population. We did not find
      substantial differences in the extent of LD in Sardinians compared with other
      populations. However, we showed that at least 9% of genomic regions in Sardinians
      differed in LD structure, which is helpful for identifying functional variants
      using fine mapping. We concluded that Sardinia is a powerful setting for genetic
      studies including GWAS and other mapping approaches.

PMID- 22378281
TI  - Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type
      4.
AB  - Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the
      combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation
      defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are
      known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB
      (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains
      unexplained at the molecular level, suggesting that other genes could be involved
      and/or that mutations within known genes may have escaped previous screenings.
      Here, we searched for deletions within recently identified SOX10 regulatory
      sequences and describe the first characterization of a WS4 patient presenting
      with a large deletion encompassing three of these enhancers. Analysis of the
      breakpoint region suggests a complex rearrangement involving three Alu sequences
      that could be mediated by a FosTes/MMBIR replication mechanism. Taken together
      with recent reports, our results demonstrate that the disruption of highly
      conserved non-coding elements located within or at a long distance from the
      coding sequences of key genes can result in several neurocristopathies. This
      opens up new routes to the molecular dissection of neural crest disorders.

PMID- 22378282
TI  - Clinical utility gene card for: Abetalipoproteinaemia.

PMID- 22378283
TI  - Methylome-wide comparison of human genomic DNA extracted from whole blood and
      from EBV-transformed lymphocyte cell lines.
AB  - DNA from Epstein-Barr virus-transformed lymphocyte cell lines (LCLs) has proven
      useful for studies of genetic sequence polymorphisms. Whether LCL DNA is suitable
      for methylation studies is less clear. We conduct a genome-wide methylation
      investigation using an array set with 45 million probes to investigate the
      methylome of LCL DNA and technical duplicates of WB DNA from the same 10
      individuals. We focus specifically on methylation sites that show variation
      between individuals and, therefore, are potentially useful as biomarkers. The
      sample correlations for the methylation variable probes ranged from 0.69 to 0.78
      for the WB duplicates and from 0.27 to 0.72 for WB vs LCL. To compare the pattern
      of the methylation signals, we grouped adjacent probes based on their inter
      correlations. These analyses showed ~29 000 and ~14 000 blocks in WB and LCL,
      respectively. Merely 31% of the methylated regions detected in WB were detectable
      in LCLs. Furthermore, we observed significant differences in mean difference
      between WB and LCL as compared with duplicates of WB (P-value =2.2 * 10(-16)).
      Our study shows that there are substantial differences in the DNA methylation
      patterns between LCL and WB. Thus, LCL DNA should not be used as a proxy for WB
      DNA in methylome-wide studies.

PMID- 22378284
TI  - SNP array-based copy number and genotype analyses for preimplantation genetic
      diagnosis of human unbalanced translocations.
AB  - Preimplantation genetic diagnosis (PGD) for chromosomal rearrangements (CR) is
      mainly based on fluorescence in situ hybridisation (FISH). Application of this
      technique is limited by the number of available fluorochromes, the extensive
      preclinical work-up and technical and interpretative artefacts. We aimed to
      develop a universal, off-the-shelf protocol for PGD by combining single
      nucleotide polymorphism (SNP) array-derived copy number (CN) determination and
      genotyping for detection of unbalanced translocations in cleavage-stage embryos.
      A total of 36 cleavage-stage embryos that were diagnosed as unbalanced by initial
      PGD FISH analysis were dissociated (n=146) and amplified by multiple displacement
      amplification (MDA). SNP CNs and genotypes were determined using SNP array.
      Epstein-Barr Virus-transformed cell lines with known CR were used for optimising
      the genomic smoothing (GS) length setting to increase signal to noise ratio. SNP
      CN analysis showed 23 embryos (64%) that were unbalanced in all blastomeres for
      the chromosomes involved in the translocation, 5 embryos (14%) that were normal
      or balanced in all blastomeres and 8 embryos (22%) that were mosaic. SNP
      genotyping, based on analysis of informative SNP loci with opposing homozygous
      parental genotypes, confirmed partial monosomies associated with inheritance of
      unbalanced translocation in surplus embryos. We have developed a universal MDA
      SNP array technique for chromosome CN analysis in single blastomeres. SNP
      genotyping could confirm partial monosomies. This combination of techniques
      showed improved diagnostic specificity compared with FISH and may provide more
      reliable PGD analysis associated with higher embryo transfer rate.

PMID- 22378286
TI  - Spontaneous disclosure of BRCA1/2 genetic test results to employers: a French
      prospective study.
AB  - The aim of this study was to examine the patterns of disclosure of BRCA1/2
      genetic test results to employers by unaffected carriers. In a national
      prospective cohort study on unaffected BRCA1/2 mutation carriers, disclosure to
      employers was assessed prospectively, using self-administered questionnaires, up
      to 2 years after their test results were delivered by cancer geneticists. Kaplan
      Meier curves and Cox-regression analysis were used to assess the factors
      associated with time to disclosure to the employer. Mean age of the 146 women
      BRCA1/2 carriers who were employed when their test results were delivered was
      37.1 years (range: 19-57). At the end of the second year of follow-up, 47 of them
      (32.2%) had disclosed their results to their employers; median time to disclosure
      was 6 months. Reasons spontaneously expressed were first to inform the employer
      that medical surveillance/surgery was necessary for cancer risk management
      although these carriers did not actually have cancer. After multivariate
      adjustment on age, women with a lower educational level (HRadj=2.00, P=0.026) and
      those who had undergone prophylactic surgery during the 2 years of follow-up
      (HRadj=2.18, P=0.019) had disclosed their BRCA status to their employers earlier
      and more frequently. One-third of the female carriers not affected by
      breast/ovarian cancer disclosed their BRCA1/2 genetic test results spontaneously
      to their employers, mainly to inform them that they were disease-free but
      required medical surveillance or a surgical intervention to reduce the risk of
      cancer.

PMID- 22378285
TI  - Mutations in the mitochondrial tRNA Ser(AGY) gene are associated with deafness,
      retinal degeneration, myopathy and epilepsy.
AB  - Although over 200 pathogenic mitochondrial DNA (mtDNA) mutations have been
      reported to date, determining the genetic aetiology of many cases of
      mitochondrial disease is still not straightforward. Here, we describe the
      investigations undertaken to uncover the underlying molecular defect(s) in two
      unrelated Caucasian patients with suspected mtDNA disease, who presented with
      similar symptoms of myopathy, deafness, neurodevelopmental delay, epilepsy,
      marked fatigue and, in one case, retinal degeneration. Histochemical and
      biochemical evidence of mitochondrial respiratory chain deficiency was observed
      in the patient muscle biopsies and both patients were discovered to harbour a
      novel heteroplasmic mitochondrial tRNA (mt-tRNA)(Ser(AGY)) (MTTS2) mutation
      (m.12264C>T and m.12261T>C, respectively). Clear segregation of the m.12261T>C
      mutation with the biochemical defect, as demonstrated by single-fibre radioactive
      RFLP, confirmed the pathogenicity of this novel variant in patient 2. However,
      unusually high levels of m.12264C>T mutation within both COX-positive (98.4 +/-
      1.5%) and COX-deficient (98.2 +/- 2.1%) fibres in patient 1 necessitated further
      functional investigations to prove its pathogenicity. Northern blot analysis
      demonstrated the detrimental effect of the m.12264C>T mutation on mt
      tRNA(Ser(AGY)) stability, ultimately resulting in decreased steady-state levels
      of fully assembled complexes I and IV, as shown by blue-native polyacrylamide gel
      electrophoresis. Our findings expand the spectrum of pathogenic mutations
      associated with the MTTS2 gene and highlight MTTS2 mutations as an important
      cause of retinal and syndromic auditory impairment.

PMID- 22378287
TI  - 19q13.11 cryptic deletion: description of two new cases and indication for a role
      of WTIP haploinsufficiency in hypospadias.
AB  - Developmental delay/intellectual disabilities, speech disturbance, pre- and
      postnatal growth retardation, microcephaly, signs of ectodermal dysplasia, and
      genital malformations in males (hypospadias) represent the phenotypic core of the
      recent emerging 19q13.11 deletion syndrome. Using array-CGH for genome-wide
      screening we detected an interstitial deletion of chromosome band 19q13.11 in two
      patients exhibiting the recognizable pattern of malformations as described in
      other instances of this submicroscopic genomic imbalance. The deletion detected
      in our patients has been compared with previously reported cases leading to the
      refinement of the minimal overlapping region (MOR) for this microdeletion
      syndrome to 324 kb. This region encompasses five genes: four zinc finger (ZNF)
      genes belonging to the KRAB-ZNF subfamily (ZNF302, ZNF181, ZNF599, and ZNF30) and
      LOC400685. On the basis of our male patient 1 and on further six male cases of
      the literature, we also highlighted that larger 19q13.11 deletions including the
      Wilms tumor interacting protein (WTIP) gene, proximal to the MOR, results in
      hypospadias making this gene a possible candidate for this genital abnormality
      due to its well-known interaction with WT1. Although the mechanism underlying the
      phenotypic effects of copy number alterations involving KRAB-ZNF genes at
      19q13.11 has not clearly been established, we suggest their haploinsufficiency as
      the most likely candidate for the phenotypic core of the 19q13.11 deletion
      syndrome. In addition, we hypothesized WTIP gene haploinsufficiency as
      responsible for hypospadias.

PMID- 22378288
TI  - DNA replication is altered in Immunodeficiency Centromeric instability Facial
      anomalies (ICF) cells carrying DNMT3B mutations.
AB  - ICF syndrome is a rare autosomal recessive disorder that is characterized by
      Immunodeficiency, Centromeric instability, and Facial anomalies. In all, 60% of
      ICF patients have mutations in the DNMT3B (DNA methyltransferase 3B) gene,
      encoding a de novo DNA methyltransferase. In ICF cells, constitutive
      heterochromatin is hypomethylated and decondensed, metaphase chromosomes undergo
      rearrangements (mainly involving juxtacentromeric regions), and more than 700
      genes are aberrantly expressed. This work shows that DNA replication is also
      altered in ICF cells: (i) heterochromatic genes replicate earlier in the S-phase;
      (ii) global replication fork speed is higher; and (iii) S-phase is shorter. These
      replication defects may result from chromatin changes that modify DNA
      accessibility to the replication machinery and/or from changes in the expression
      level of genes involved in DNA replication. This work highlights the interest of
      using ICF cells as a model to investigate how DNA methylation regulates DNA
      replication in humans.

PMID- 22378289
TI  - Reply to Ross' commentary: Reproductive benefit through newborn screening:
      preferences, policy and ethics.

PMID- 22378291
TI  - PPARgamma2 gene Pro12Ala and PPARalpha gene Leu162Val single nucleotide
      polymorphisms interact with dietary intake of fat in determination of plasma
      lipid concentrations.
AB  - BACKGROUND/AIMS: The peroxisome proliferator-activated receptors (PPARs) are
      transcriptional regulators of lipid metabolism, activated by unsaturated fatty
      acids. We investigated independent and interactive effects of PPARgamma2 gene
      PPARG Pro12Ala (rs1801282) andPPARalphagene PPARA Leu162Val (rs1800206) genotypes
      with dietary intake of fatty acids on concentrations of plasma lipids in subjects
      of whom 47.5% had metabolic syndrome. METHODS: The RISCK study is a parallel
      design, randomised controlled trial. Plasma lipids were quantified at baseline
      after a 4-week high saturated fatty acids diet and after three parallel 24-week
      interventions with reference (high saturated fatty acids), high monounsaturated
      fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in
      466 subjects. RESULTS: At baseline, the PPARG Ala12allele was associated with
      increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p =
      0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At
      baseline, PPARA Leu162Val * PPARG Pro12Ala genotype interaction did not
      significantly influence plasma lipid concentrations. After dietary intervention,
      gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and
      small dense LDL as a proportion of LDL (p = 0.005) after adjustments.
      CONCLUSIONS: Interaction between PPARG Pro12Ala and PPARA Leu162Val genotypes may
      influence plasma LDL cholesterol concentration and the proportion as small dense
      LDL after a high monounsaturated fatty acids diet.

PMID- 22378292
TI  - Ciprofloxacin and epirubicin synergistically induce apoptosis in human urothelial
      cancer cell lines.
AB  - INTRODUCTION: Few published in vitro studies have shown antitumor drug action or
      possible synergistic effects of fluoroquinolones. To assess the potential role of
      combination therapy, cytotoxic effects of ciprofloxacin and epirubicin alone and
      in combination were determined. MATERIAL AND METHODS: Human urothelial cancer
      cell lines HT1197 and HT1376 were exposed in vitro for 1 h to different
      concentrations of epirubicin (0.02-2 mg/ml) and for 72 h to ciprofloxacin (0.004
      0.8 mg/ml). Cytotoxicity was determined using the microculture tetrazolium assay
      and flow cytometry. Synergistic cytotoxic effects were determined by calculating
      combination indices. RESULTS: Median effect concentrations of epirubicin for
      HT1376 and HT1197 cells were as low as 124 and 117 MUg/ml, respectively.
      Ciprofloxacin-treated cells exhibited profound cytotoxic effects at
      concentrations of 50-100 MUg/ml, which is far below the intravesical
      concentration reached by standard oral application. In addition, a pronounced
      synergistic effect was found when the two treatments were combined. CONCLUSIONS:
      This study provides evidence that ciprofloxacin and epirubicin exhibit
      synergistic cytotoxic effects in vitro. After confirmatory animal experiments,
      future clinical studies of adjuvant chemotherapy after transurethral bladder
      resection may include treatment arms with combinations of fluoroquinolones based
      on the observed synergistic effects to reduce both side effects and costs.

PMID- 22378290
TI  - Gucy2f zebrafish knockdown--a model for Gucy2d-related leber congenital
      amaurosis.
AB  - Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with
      Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative
      to rodents, including their excellent color vision, precocious retinal
      development, robust visual testing strategies, low cost, relatively easy
      transgenesis and shortened experimental times. In this study we will demonstrate
      the feasibility of using gene-targeting in the zebrafish as a model for the
      photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and
      retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA
      orthologous cDNA was identified and isolated by PCR amplification. Its expression
      pattern was determined by whole-mount in-situ hybridization and its function was
      studied by gene knockdown using two different morpholino-modified oligos (MO),
      one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f.
      Visual function was assessed with an optomotor assay on 6-days-post-fertilization
      larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted
      in significantly lower vision as measured by the optomotor response compared with
      uninjected and control MO-injected zebrafish larvae. Histological changes in the
      Gucy2f-knockdown larvae included loss and shortening of cone and rod outer
      segments. A zebrafish model of Gucy2f-related LCA1 displays early visual
      dysfunction and photoreceptor layer dystrophy. This study serves as proof of
      concept for the use of zebrafish as a simple, inexpensive model with excellent
      vision on which further study of LCA-related genes is possible.

PMID- 22378293
TI  - Impact of vascular calcification on QT interval and QT dispersion in CKD and
      dialysis patients.

PMID- 22378294
TI  - Chemical methods for degradation of target oligosaccharides using designed light
      activatable organic molecules.
AB  - Carbohydrates play crucial roles in a wide range of biological processes,
      including serious diseases. The development of novel and innovative methods for
      selective control of specific oligosaccharide functions has attracted much
      attention in the fields of chemistry, biology, and medicine. In this feature
      article, the development of novel chemical tools, which can degrade target
      oligosaccharides by irradiation with a specific wavelength of light under mild
      conditions without any additives, is introduced. This novel class of
      photochemical agents promise bright prospects for finding not only molecular
      targeted bioprobes for understanding of the structure-activity relationships of
      oligosaccharides but also novel therapeutic drugs targeting oligosaccharides.

PMID- 22378295
TI  - A non-damaging method to analyze the configuration and dynamics of nitrotyrosines
      in proteins.
AB  - Often, deregulation of protein activity and turnover by tyrosine nitration drives
      cells toward pathogenesis. Hence, understanding how the nitration of a protein
      affects both its function and stability is of outstanding interest. Nowadays,
      most of the in vitro analyses of nitrated proteins rely on chemical treatment of
      native proteins with an excess of a chemical reagent. One such reagent,
      peroxynitrite, stands out for its biological relevance. However, given the excess
      of the nitrating reagent, the resulting in vitro modification could differ from
      the physiological nitration. Here, we determine unequivocally the configuration
      of distinct nitrated-tyrosine rings in single-tyrosine mutants of cytochrome c.
      We aimed to confirm the nitration position by a non-destructive method. Thus, we
      have resorted to (1)H-(15)N heteronuclear single quantum coherence(HSQC) spectra
      to identify the (3)J(N?H) correlation between a (15)N-tagged nitro group and the
      adjacent aromatic proton. Once the chemical shift of this proton was determined,
      we compared the (1)H-(13)C HSQC spectra of untreated and nitrated samples. All
      tyrosines were nitrated at epsilon positions, in agreement to previous analysis
      by indirect techniques. Notably, the various nitrotyrosine residues show a
      different dynamic behaviour that is consistent with molecular dynamics
      computations.

PMID- 22378296
TI  - Structured coculture of mesenchymal stem cells and disc cells enhances
      differentiation and proliferation.
AB  - PURPOSE: During in vivo stem cell differentiation, mature cells often induce the
      differentiation of nearby stem cells. Accordingly, prior studies indicate that a
      randomly mixed coculture can help transform mesenchymal stem cells (MSC) into
      nucleus pulposus cells (NPC). However, because in vivo signaling typically occurs
      heterotopically between adjacent cell layers, we hypothesized that a structurally
      organized coculture between MSC and NPC will result in greater cell
      differentiation and proliferation over single cell-type controls and cocultures
      with random organization. METHODS: We developed a novel bilaminar cell pellet
      (BCP) system where a sphere of MSC is enclosed in a shell of NPC by successive
      centrifugation. Controls were made using single cell-type pellets and coculture
      pellets with random organization. The pellets were evaluated for DNA content,
      gene expression, and histology. RESULTS: A bilaminar 3D organization enhanced
      cell proliferation and differentiation. BCP showed significantly more cell
      proliferation than pellets with one cell type and those with random organization.
      Enhanced differentiation of MSC within the BCP pellet relative to single cell
      type pellets was demonstrated by quantitative RT-PCR, histology, and in situ
      hybridization. CONCLUSIONS: The BCP culture system increases MSC proliferation
      and differentiation as compared to single cell type or randomly mixed coculture
      controls.

PMID- 22378297
TI  - Who protects physicians and patients from guidelines?

PMID- 22378299
TI  - Transcranial focused ultrasound to the thalamus is associated with reduced
      extracellular GABA levels in rats.
AB  - OBJECTIVE: Transcranial focused ultrasound (FUS), with its ability to non
      invasively modulate the excitability of region-specific brain areas, is gaining
      attention as a potential neurotherapeutic modality. The aim of this study was to
      examine whether or not FUS administered to the brain could alter the
      extracellular levels of glutamate and gamma-aminobutyric acid (GABA), which are
      representative excitatory and inhibitory amino acid neurotransmitters,
      respectively. METHODS: FUS, delivered in the form of a train of pulses, was
      applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA
      were directly sampled from the frontal lobe of the rat brain via a direct
      microdialysis technique before, during, and after the sonication. The dialysate
      concentrations were determined by high-performance liquid chromatography.
      RESULTS: The individual levels of the neurotransmitters sampled were normalized
      to the baseline level for each rat. In terms of the changes in extracellular
      glutamate levels, there was no difference between the FUS-treated group and the
      unsonicated control group. However, extracellular GABA levels started to decrease
      upon sonication and remained reduced (approximately 20% below baseline; repeated
      measures ANOVA, p < 0.05, adjusted for multiple comparisons) compared to the
      control group. CONCLUSION: The ability to modulate region-specific brain
      activity, along with the present evidence of the ability to modulate
      neurotransmission, demonstrates the potential utility of FUS as a completely new
      non-invasive therapeutic modality.

PMID- 22378298
TI  - Blood-brain barrier dysfunction, TGFbeta signaling, and astrocyte dysfunction in
      epilepsy.
AB  - Brain insults, including traumatic and ischemic injuries, are frequently followed
      by acute seizures and delayed development of epilepsy. Dysfunction of the blood
      brain barrier (BBB) is a hallmark of brain insults and is usually surrounding the
      core lesion. Recent studies from several laboratories confirmed that vascular
      pathology is involved in the development of epilepsy and demonstrate a key role
      for astroglia in this process. In this review, we focus on glia-related
      mechanisms linking vascular pathology, and specifically BBB dysfunction, to
      seizures and epilepsy. We summarize molecular and physiological experimental data
      demonstrating that the function of astrocytes is altered due to direct exposure
      to serum albumin, mediated by transforming growth factor beta signaling. We
      discuss the reported changes and their potential role in the observed
      hyperexcitability as well as potential implications of these findings for the
      future development of new diagnostic modalities and treatments to allow a full
      implementation of the gained knowledge for the benefit of patients with epilepsy.

PMID- 22378300
TI  - Involvement of Mcl1 in diallyl disulfide-induced G2/M cell cycle arrest in HL-60
      cells.
AB  - Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various
      cancers. Previously, we found that myeloid cell leukemia sequence 1 (Mcl1) was
      downregulated in DADS-induced cell cycle arrest in HL-60 human leukemia cells.
      Here, we investigated the role of this protein in DADS-induced G2/M cell cycle
      arrest in HL-60 cells. We demonstrated that DADS treatment significantly
      increased the proportion of G2/M phase HL-60 cells (P<0.05) and caused a time
      dependent significant downregulation of Mcl1 and the cell cycle-related proteins
      PCNA and CDK1 (P<0.05). Small interfering RNA-mediated knockdown of Mcl1
      expression in HL-60 cells arrested the cell cycle in G2/M phase. By co
      immunoprecipitation, we demonstrated that Mcl1 associated with PCNA and CDK1 in
      G2/M cell cycle arrest in DADS-treated HL-60 cells. DADS decreased the
      interaction of Mcl1 with PCNA and CDK1, leading to G2/M cell cycle arrest in HL
      60 cells. Mcl1 plays an important role in DADS-induced G2/M cell cycle arrest in
      HL-60 human leukemia cells.

PMID- 22378302
TI  - Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic
      cancer xenograft model in vivo via inhibition of inhibitors of apoptosis.
AB  - Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is
      currently the standard first-line chemotherapeutic agent for pancreatic cancer.
      As members of apoptosis inhibitors, Survivin and XIAP play an important role in
      chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential
      against cancers. This study was designed to investigate whether combination
      therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic
      cancer. The application of the combination therapy triggered significantly higher
      frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the
      combination of emodin and gemcitabine resulted in significantly reduced tumor
      volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry
      and western immunoblot analyses showed that Survivin and XIAP expression were
      downregulated in emodin and the combination groups compared to the other two
      groups. Reverse transcriptase polymerase chain reaction analyses showed that
      Survivin and XIAP mRNA expression in emodin and the combination groups were
      downregulated significantly compared to the other two groups. Furthermore, the
      expression of the nuclear transcription factor kappaB (NF-kappaB) protein and NF
      kappaB mRNA were downregulated in the emodin and the combination groups. DNA
      binding activity of NF-kappaB was inhibited in emodin and combination groups
      compared to the other groups. This study suggests that emodin potentiates the
      antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of
      apoptosis and IAP suppression.

PMID- 22378306
TI  - Pd-catalyzed and CsF-promoted reaction of bromoalkynes with isocyanides:
      regioselective synthesis of substituted 5-iminopyrrolones.
AB  - The palladium-catalyzed and CsF-promoted annulation reaction of bromoalkynes and
      isocyanides regioselectively affords a diverse set of 5-iminopyrrolone
      derivatives. This chemistry presumably proceeds through the bromoacrylamide
      intermediates, which can be readily prepared from the nucleophilic addition
      reaction of isocyanides to bromoalkynes in the presence of CsF.

PMID- 22378307
TI  - Phenotypic and genetic relationships between kidney function and carotid intima
      media thickness in Koreans: the Healthy Twin Study.
AB  - BACKGROUND: The phenotypic and genetic relationships between carotid intima-media
      thickness (CIMT) and estimated glomerular filtration rate (eGFR) or urinary
      albumin-creatinine ratio (ACR) were evaluated in Korean twins and families.
      METHODS: We recruited 688 participants (296 individual twins and 392 singletons,
      age 30-74 years) who were without myocardial infarction and stroke among
      participants in the Healthy Twin Study. eGFR was calculated using the Chronic
      Kidney Disease Epidemiology Collaboration equation. CIMT was measured using B
      mode carotid ultrasound. Covariates were sex, Framingham risk scores, alcohol
      use, exercise, BMI, high-sensitivity C-reactive protein and triglycerides.
      Quantitative genetic and linear mixed analyses were performed. RESULTS: In
      adjusted models there were associations between kidney function and CIMT with
      [beta] estimates ranging from -0.022 to -0.032 between eGFR and CIMT, and from
      0.042-0.060 between ACR and CIMT. The covariate-adjusted heritabilities for eGFR,
      ACR and composite CIMT were 0.75, 0.32 and 0.45, respectively (p < 0.001). The
      adjusted genetic correlation between eGFR and CIMT was from -0.20 to -0.28 (p <
      0.05), whereas there was no genetic correlation between ACR and CIMT. CONCLUSION:
      Kidney function is a surrogate marker of carotid atherosclerosis and further
      studies of the pleiotropic relationships between CIMT and eGFR are warranted.

PMID- 22378308
TI  - New insights on translational development of mesenchymal stromal cells for
      suppressor therapy.
AB  - The discovery of the immunosuppressive properties of mesenchymal stromal cells
      (MSCs) has given new hope to patients suffering from autoimmune diseases as their
      lack of immunogenicity in addition to their immunosuppressive and regenerative
      properties makes them an ideal biological agent for the treatment of various
      disorders ranging from autoimmune diseases to tissue injury. The translational
      promises of a safer and more effective therapy has however suffered a setback
      with the recent release of the results from Phase III randomized clinical trial
      using MSCs for treatment of steroid refractory acute graft-versus-host disease
      (GvHD), which failed to meet its primary efficacy endpoint. In this review, we
      will address the current knowledge of the immunosuppressive mechanisms of MSCs
      from in vitro studies to animal models and then look upon the results obtained
      from human clinical trials in order to provide failure analysis of negative
      studies. We will conclude by proposing future directions which could help address
      this issue and allow rational development of MSCs as an effective and useful cell
      based immunotherapeutic.

PMID- 22378309
TI  - Hormonal evaluation in premature ejaculation.
AB  - INTRODUCTION: Premature ejaculation (PE) is a frequently encountered sexual
      dysfunction in men. It significantly impairs quality of life of the affected male
      and his partner. The aim of this study is to investigate the role of hormonal
      factors in patients with PE. PATIENTS AND METHODS: 107 male patients aged between
      26 and 64 years (mean 45.1 +/- 10.36) who consulted our outpatient clinics with
      complaints of PE and 94 healthy males (48.1 +/- 11.81 years) as a control group
      were included in the study. RESULTS: When mean serum hormone concentrations of
      both groups were compared, levels of prolactin and free T4 were found to be
      significantly higher in the PE group relative to the control group (p < 0.05). At
      least one of the hormonal parameters was abnormal in 36 cases (33.6%) with PE,
      compared to only 22 (23.4%) of the controls. The number of hyperprolactinemic
      cases was found to be significantly increased in the PE group (p < 0.05).
      CONCLUSION: We feel that during the evaluation of this problem, which affects
      great numbers of men and their partners throughout the world, consideration of
      potential effects of hormonal factors might be beneficial.

PMID- 22378310
TI  - Factors predicting erythropoietin resistance among maintenance hemodialysis
      patients.
AB  - BACKGROUND: Erythropoiesis-stimulating agent (ESA) resistance remains
      incompletely understood among hemodialysis (HD) patients. METHOD: A
      retrospective, multicenter study was designed to analyze data from 1,934 patients
      followed for up to two years. The outcome measure was the erythropoietin
      resistance index (ERI), defined as erythropoietin dosage over a week divided by
      the post-HD weight and hemoglobin value. RESULTS: Multivariate analysis revealed
      albumin, Kt/V, transferrin saturation, statin use and male gender to be inversely
      related to ERI, whereas parathyroid hormone and angiotensin-converting enzyme
      inhibitors (ACEI)/angiotensin receptor blockers (ARB) use were associated with
      higher ESA resistance. ERI was statistically lower in patients with higher levels
      of albumin (p < 0.001) and with higher transferrin saturation levels (p < 0.05).
      DISCUSSION: The results allow for a better understanding of predictors of
      erythropoietin resistance among HD patients including not extensively studied
      factors such as statin and ACEI/ARB use.

PMID- 22378311
TI  - Ruthenium(II) photosensitizers of tridentate click-derived cyclometalating
      ligands: a joint experimental and computational study.
AB  - A systematic series of heteroleptic bis(tridentate)ruthenium(II) complexes of
      click-derived 1,3-bis(1,2,3-triazol-4-yl)benzene N^C^N-coordinating ligands was
      synthesized, analyzed by single crystal X-ray diffraction, investigated
      photophysically and electrochemically, and studied by computational methods. The
      presented comprehensive characterization allows a more detailed understanding of
      the radiationless deactivation mechanisms. Furthermore, we provide a fully
      optimized synthesis and systematic variations towards redox-matched, broadly and
      intensely absorbing, cyclometalated ruthenium(II) complexes. Most of them show a
      weak room-temperature emission and a prolonged excited-state lifetime. They
      display a broad absorption up to 700 nm and high molar extinction coefficients up
      to 20 000 M(-1)cm(-1) of the metal-to-ligand charge transfer bands, resulting in
      a black color. Thus, the complexes reveal great potential for dye-sensitized
      solar-cell applications.

PMID- 22378312
TI  - Comparison of adjustment methods for stratified two-sample tests in the context
      of ROC analysis.
AB  - We compare several nonparametric and parametric weighting methods for the
      adjustment of the effect of strata. In particular, we focus on the adjustment
      methods in the context of receiver-operating characteristic (ROC) analysis.
      Nonparametrically, rank-based van Elteren's test and inverse-variance (IV)
      weighting using the area under the ROC curve (AUC) are examined. Parametrically,
      the stratified t-test and IV AUC weighted method are applied based on a binormal
      monotone transformation model. Stratum-specific, pooled, and adjusted estimates
      are obtained. The pooled and adjusted AUCs are estimated. We illustrate and
      compare these weighting methods on a multi-center diagnostic trial and through
      extensive Monte-Carlo simulations.

PMID- 22378313
TI  - Phenotype and genotype characterization and twin association in patients with
      Anderson-Fabry cardiomyopathy.
AB  - Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder
      caused by a deficiency of alpha-galactosidase A (alpha-Gal A) activity, is
      associated with cardiac manifestations including arrhythmias, valvular
      abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy
      (ERT) may have the potential to delay the underlying clinical outcomes in
      patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used
      to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring
      the alpha-Gal A activity in plasma and mutation analysis by direct sequencing
      using capillary electrophoresis. We identified four adult hemizygous male
      patients with cardiomyopathy and other symptoms related to FD; two of them were
      monozygotic twins. In all cases, ECG and echocardiography showed severe left
      ventricular (LV) hypertrophy. Some years later, all patients showed typical
      symptoms of FD, including angiokeratomas and neurological, renal,
      gastrointestinal, and ocular involvement. A deficiency of alpha-Gal A activity
      and point mutations in exon 5 of the GLA gene were detected in all patients. ERT
      (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous
      infusion over 40 min. In conclusion, these findings highlight the importance of
      screening middle-aged patients with LV hypertrophy for the early detection of FD,
      particularly in direct-line relatives such as twins.

PMID- 22378314
TI  - Endoplasmic reticulum stress impairs insulin signaling through mitochondrial
      damage in SH-SY5Y cells.
AB  - Endoplasmic reticulum (ER) and mitochondrial stress are considered causal factors
      that induce neurodegenerative diseases. However, the relationship between these
      stresses remains poorly understood. To investigate the molecular mechanism
      underlying crosstalk between the ER and mitochondria in neurodegeneration, we
      treated SH-SY5Y human neuroblastoma cells with thapsigargin and tunicamycin, two
      inducers of ER stress, and atrazine, a promoter of mitochondrial stress. Each
      pharmacological agent caused mitochondrial dysfunction, which was characterized
      by reduced intracellular ATP, mitochondrial membrane potential, and endogenous
      cellular respiration as well as an augmentation of oxidative stress.
      Oligonucleotide microarray analysis followed by semiquantitative RT-PCR
      validation assays revealed that thapsigargin and tunicamycin downregulated the
      expression of most mitochondria-related genes in a manner similar to that induced
      by atrazine. In contrast, atrazine did not alter the expression of markers of ER
      stress. Three-dimensional principal component analysis showed that the gene
      expression profile produced by atrazine treatment was distinct from that
      generated by ER stress. However, all three agents impaired insulin receptor
      substrate-1 and Akt phosphorylation in the insulin signaling pathway. Ectopic
      overexpression of mitochondrial transcription factor A reversed the effects of
      thapsigargin on mitochondria and Akt signaling. We conclude that ER stress
      induces neuronal cell death through common perturbation of mitochondrial function
      and Akt signaling.

PMID- 22378315
TI  - New craniodental material of Pronothodectes gaoi Fox (Mammalia,
      "Plesiadapiformes") and relationships among members of Plesiadapidae.
AB  - Plesiadapidae are a family of Paleogene mammals thought to have phylogenetic
      affinities with modern Primates. We describe previously unpublished dentitions
      and the first skull and isolated petrosals of the plesiadapid Pronothodectes
      gaoi, collected from middle Tiffanian localities of the Paskapoo Formation in
      Alberta. Other species of Pronothodectes, traditionally considered the most basal
      members of the Plesiadapidae, occur at earlier, Torrejonian horizons in Montana,
      Wyoming, and Alberta. Classification of P. gaoi as a species of Pronothodectes
      has proved controversial; accordingly, we use the newly available samples and the
      more extensively preserved specimens to re-evaluate the generic affinities of
      this species. Included in our study are comparisons with craniodental material
      known for other plesiadapids and plesiadapiforms. Cladistic analysis of
      craniodental characters is used to assess the hypothesis that P. gaoi and other
      species in this genus are basal members of the Plesiadapidae. The new dental
      evidence confirms that P. gaoi lacks derived character states of other
      plesiadapids except for a variably present fissuring of the m3 hypoconulid.
      Moreover, several aspects of the cranium seem to be more primitive in P. gaoi
      (i.e., more like nonplesiadapid plesiadapiforms) than in later occurring
      plesiadapids, such as Plesiadapis tricuspidens and Plesiadapis cookei. Cladistic
      analysis of craniodental morphology supports a basal position of P. gaoi among
      species of Plesiadapidae, with the exception of other species of Pronothodectes.
      The basicranium of P. gaoi preserves a laterally placed bony canal for the
      internal carotid neurovascular system, suggesting that this was the ancestral
      condition for the family.

PMID- 22378316
TI  - Radiological patterns of primary graft dysfunction after lung transplantation
      evaluated by 64-multi-slice computed tomography: a descriptive study.
AB  - We evaluated the diagnostic value of high-resolution computed tomography (HRCT)
      images generated from 64 detector multi-slice CT scanners (HRCT(64-MSCT) imaging)
      in relation to primary graft dysfunction (PGD) after lung-transplantation (LUTX)
      in a pilot study. PGD has mortality rates ranging from 17 to 50% over a 90-day
      period. Detailed HRCT lung images, reconstructed using 64-MSCT, may aid
      diagnostic and therapeutic efforts in PGD. Thirty-two patients were scanned four
      times within a year post-LUTX, in a single-centre prospective study. HRCT lung
      images were reviewed, evaluated and scored by two observers, for ground-glass
      (GG) opacities, consolidation, septal thickening (ST) and pulmonary embolism.
      Image and PGD scores were compared in each patient. GG and consolidation changes
      were largely present up until 2 weeks post-LUTX, and markedly reduced by the 12th
      week. ST was predominantly found in patients with PGD. There were no vascular
      changes found at CT angiographies. The most severe cases of GG opacities and
      consolidation were found in patients with PGD. ST seems to be an important
      indicator of PGD. HRCT(64-MSCT) imaging may be a useful tool for the
      identification of pathological features of PGD not detected by classical
      evaluation in patients undergoing LUTX.

PMID- 22378317
TI  - Double aortic arch in an adult.
AB  - We present the case of a 60-year old man who complained of severe dysphagia
      caused by a double aortic arch (DAA) with a right-sided descending thoracic
      aorta. The left-sided aortic arch had a compressive segment located between the
      left subclavian artery and the descending thoracic aorta. Using left third
      thoracotomy, the segment, which caused compression of the oesophagus, was ligated
      and divided. After the operation, the patient was completely relieved of his
      symptoms. We concluded that the removal of the compressive portion of the left
      aortic arch and the ligation of the ligamentum arteriosum are the only treatment
      measures needed in such cases.

PMID- 22378318
TI  - How to do it: direct true lumen cannulation technique of the ascending aorta in
      acute aortic dissection type A.
AB  - In acute aortic dissection type A (AADA), direct true lumen cannulation (DTLC) of
      the ascending aorta is a fast and safe cannulation site providing antegrade
      perfusion of the supraaortic and visceral vessels. An Overholt clamp is passed
      around the ascending aorta to place a Mersilene tape for later securing of the
      arterial cannula. After draining venous blood into the cardiopulmonary bypass
      system (CPB), the ascending aorta is transected and the aortic lumen inspected.
      The true lumen is identified and an arterial cannula inserted directly. Finally,
      the cannula is secured with the previously placed tape and CPB is initiated. DTLC
      can be used as arterial cannulation standard technique in operations for AADA.

PMID- 22378319
TI  - Unusual clinical behaviour of thymoma with recurrent myasthenia gravis.
AB  - A 58-year old man with thymoma and myasthenia gravis (MG) had undergone
      thymectomy 8 years ago with histopathologically confirmed non-invasive WHO-type
      AB thymoma. After 5 years of complete remission, symptoms of MG resurfaced, and a
      recurrent anterior mediastinal mass was detected for which he received
      radiotherapy. He presented to us 3 years later with productive cough and
      exertional dyspnoea; the positron emission tomography-computed tomography scan
      revealed a metabolically active pulmonary nodule in the right lung as the only
      site of disease for which a right lower lobectomy was done. Microscopy
      established an intrapulmonary WHO-type B2 thymoma and the patient is currently
      asymptomatic on steroids, anticholinesterase and immunosuppressant therapy. We
      discuss the variable and unpredictable course of thymomas; the possibility of
      transformation into more aggressive types with each recurrence, association with
      recurrent MG post-thymectomy and presentation several years later with metastatic
      disease.

PMID- 22378320
TI  - In vivo and in situ imaging of head and neck squamous cell carcinoma using near
      infrared fluorescent quantum dot probes conjugated with epidermal growth factor
      receptor monoclonal antibodies in mice.
AB  - In this study, we applied near-infrared fluorescent quantum dots (NIRF-QDs) for
      non-invasive in vivo and in situ imaging of head and neck squamous cell carcinoma
      (HNSCC). The U14 squamous cancer cell line with high expression of epidermal
      growth factor receptor (EGFR) was implanted subcutaneously into the head and neck
      regions of nude mice to establish HNSCC models. NIRF-QDs with an emission
      wavelength of 800 nm (NIRF-QD800) were conjugated with EGFR monoclonal antibodies
      to develop the QD800-EGFR Ab probe. In vivo and in vitro studies demonstrated
      that the QD800-EGFR Ab probe can specifically bind EGFR expressed on U14 cells.
      U14 squamous cell carcinoma in the head and neck can be clearly visualized by in
      vivo imaging after intravenous injection of QD800-EGFR Ab probes. The results
      suggested that in situ imaging using NIRF-QD-EGFR Ab probes has unique advantages
      and prospects for the investigation of tumor development, early diagnosis and
      personalized therapy of HNSCC.

PMID- 22378321
TI  - Perioperative antibiotic in adenoidectomy with partial tonsillectomy: a
      randomized trial.
AB  - OBJECTIVES: To examine potential benefits of perioperative antibiotic therapy in
      children undergoing adenotonsillotomy. METHODS: Adenoidectomy with tonsillotomy
      was performed in 124 children with obstructive symptoms, aged 5-7 years. Of
      these, 120 completed the study. Intraoperative intravenous and postoperative oral
      clindamycin, or placebo for 7 days, were administered. RESULTS: There were
      significant differences between the groups regarding pain intensity (p < 0.001)
      and duration (p < 0.05), day of return to normal physical activity (p < 0.05),
      occurrence and duration of oral malodor (p < 0.001), number of doses of
      additional analgesic (p < 0.001), healing grading (p < 0.05) and
      parents'/caregivers' satisfaction scores on the 4th postoperative day. There were
      indications for antibiotic in 2 individuals in the placebo group. CONCLUSIONS:
      There are significant differences in the course of convalescence related to
      perioperative antibiotic in children after adenotonsillotomy, but strict
      indications for antibiotics in these patients are rare.

PMID- 22378322
TI  - Developmental origins of obesity: early feeding environments, infant growth, and
      the intestinal microbiome.
AB  - OBJECTIVES: Pediatric overweight and obesity are growing problems worldwide, with
      increasing prevalence among even infants and young children. The refractory
      nature of early overweight necessitates identifying the factors contributing to
      early excess weight gain for successful intervention. Early feeding practices may
      be particularly important in shaping long-term vulnerability to obesity. How and
      what infants are fed can influence weight gain, adiposity, and energy metabolism
      during infancy and across the life course through a number of interacting
      physiological and behavioral pathways. This article argues that these biological
      mechanisms interact with the social and behavioral context of infant feeding to
      create differential vulnerability to later obesity. METHODS: This article reviews
      recent research on the potential mechanisms linking infant feeding and risk of
      later obesity, focusing on the emerging role of microflora colonization. RESULTS:
      The nutritive and non-nutritive components of breastmilk, formula and solid foods
      and the practices surrounding feeding shape the infant metabolome, programming
      growth rates and body composition, altering metabolism and physiology, promoting
      differential microfloral colonization, and shaping behavioral responses to foods
      and eating. CONCLUSION: The occurrence of chronic disease precursors at
      increasingly younger ages and the tendency of overweight young children to become
      overweight adolescents and adults underscore the importance of understanding this
      complex early exposure and intervening early to prevent the development of
      obesity in increasingly weight-promoting environments.

PMID- 22378323
TI  - Ligand effects on the dimensionality of oxamato-bridged mixed-metal open
      framework magnets.
AB  - Increasing dimensionality [from 2D (1) to 3D (2)] and T(C) [from 10 (1) to 20 K
      (2)] in two new oxamato-bridged heterobimetallic Mn(II)(2)Cu(II)(3) open
      frameworks result from the steric hindrance provided by the different alkyl
      substituents of the N-phenyloxamate bridging ligands.

PMID- 22378324
TI  - Global iodine status in 2011 and trends over the past decade.
AB  - Salt iodization has been introduced in many countries to control iodine
      deficiency. Our aim was to assess global and regional iodine status as of 2011
      and compare it to previous WHO estimates from 2003 and 2007. Using the network of
      national focal points of the International Council for the Control of Iodine
      Deficiency Disorders as well as a literature search, we compiled new national
      data on urinary iodine concentration (UIC) to add to the existing data in the WHO
      Vitamin and Mineral Nutrition Information System Micronutrients Database. The
      most recent data on UIC, primarily national data in school-age children (SAC),
      were analyzed. The median UIC was used to classify national iodine status and the
      UIC distribution to estimate the number of individuals with low iodine intakes by
      severity categories. Survey data on UIC cover 96.1% of the world's population of
      SAC, and since 2007, new national data are available for 58 countries, including
      Canada, Pakistan, the U.K., and the U.S.. At the national level, there has been
      major progress: from 2003 to 2011, the number of iodine-deficient countries
      decreased from 54 to 32 and the number of countries with adequate iodine intake
      increased from 67 to 105. However, globally, 29.8% (95% CI = 29.4, 30.1) of SAC
      (241 million) are estimated to have insufficient iodine intakes. Sharp regional
      differences persist; southeast Asia has the largest number of SAC with low iodine
      intakes (76 million) and there has been little progress in Africa, where 39% (58
      million) have inadequate iodine intakes. In summary, although iodine nutrition
      has been improving since 2003, global progress may be slowing. Intervention
      programs need to be extended to reach the nearly one-third of the global
      population that still has inadequate iodine intakes.

PMID- 22378325
TI  - Genetic hemoglobin disorders, infection, and deficiencies of iron and vitamin A
      determine anemia in young Cambodian children.
AB  - In Cambodia, many factors may complicate the detection of iron deficiency. In a
      cross-sectional survey, we assessed the role of genetic hemoglobin (Hb)
      disorders, iron deficiency, vitamin A deficiency, infections, and other factors
      on Hb in young Cambodian children. Data on sociodemographic status, morbidity,
      and growth were collected from children (n = 3124) aged 6 to 59 mo selected from
      3 rural provinces and Phnom Penh municipality. Blood samples were collected (n =
      2695) for complete blood count, Hb type (by DNA analysis), ferritin, soluble
      transferrin receptor (sTfR), retinol-binding protein (RBP), C-reactive protein,
      and alpha(1)-acid glycoprotein (AGP). Genetic Hb disorders, anemia, and vitamin A
      deficiency were more common in rural than in urban provinces (P < 0.001): 60.0
      vs. 40.0%, 58.2 vs. 32.7%, and 7.4 vs. 3.1%, respectively. Major determinants of
      Hb were age group, Hb type, ferritin, sTfR, RBP, AGP >1.0 g/L (P < 0.001), and
      rural setting (P < 0.05). Age group, Hb type, RBP, elevated AGP, and rural
      setting also influenced ferritin and sTfR (P < 0.02). Multiple factors affected
      anemia status, including the following: age groups 6-11.99 mo (OR: 6.1; 95% CI:
      4.3, 8.7) and 12-23.99 mo (OR: 2.7; 95% CI: 2.1, 3.6); Hb type, notably Hb EE
      (OR: 18.5; 95% CI: 8.5, 40.4); low ferritin (OR: 3.2; 95% CI: 2.2, 4.7); elevated
      AGP (OR: 1.4; 95% CI: 1.2,1.7); rural setting (OR: 2.3; 95% CI: 1.7, 3.1); low
      RBP (OR: 3.6; 95% CI: 2.2, 5.9); and elevated sTfR (OR: 2.1; 95% CI: 1.7, 2.7).
      In Cambodia, where a high prevalence of genetic Hb disorders exists, ferritin and
      sTfR are of limited use for assessing the prevalence of iron deficiency. New low
      cost methods for detecting genetic Hb disorders are urgently required.

PMID- 22378326
TI  - Dietary fish oil decreases the proportion of classical monocytes in blood in
      healthy mice but increases their proportion upon induction of inflammation.
AB  - Fish oil can have beneficial effects in health and disease. In healthy
      individuals, reduction of the inflammatory status may be of benefit, whereas in
      patients with systemic inflammation, such as sepsis, it is important to diminish
      the immunosuppression that is thought to contribute to poor outcome. The
      objective of this study was to determine the effects of dietary fish oil on
      monocytes/macrophages in blood, bone marrow, spleen, and peritoneum and chemokine
      concentrations in blood and peritoneum in healthy mice and mice with endotoxin
      induced inflammation. Mice were fed a Western-type diet without fish oil (C) or
      with 2.8% fish oil (FO) for 6 wk and then either killed (healthy mice) or
      injected i.p. with endotoxin (LPS) and killed after 3, 8, 12, 24, or 48 h. Blood,
      bone marrow, spleen, and peritoneal lavage were collected. Expression of cell
      surface molecules and chemokine receptors was analyzed by flow cytometry and
      chemokine concentrations measured by ELISA. Healthy mice in the FO group had
      lower proportions of classical monocytes in blood than healthy mice in the C
      group. LPS administration increased the proportion of classical monocytes in
      blood in mice in the FO group but not in those in the C group. Healthy mice in
      the FO group had lower serum concentrations of CCL2 than mice in the C group, but
      in inflamed mice, CCL2 concentrations were higher in the FO group than in the C
      group. These results indicate that dietary fish oil can attenuate the
      inflammatory status in homeostasis but intensify the immune response upon
      inflammation.

PMID- 22378327
TI  - Coffee extract attenuates changes in cardiovascular and hepatic structure and
      function without decreasing obesity in high-carbohydrate, high-fat diet-fed male
      rats.
AB  - Coffee, a rich source of natural products, including caffeine, chlorogenic acid,
      and diterpenoid alcohols, has been part of the human diet since the 15th century.
      In this study, we characterized the effects of Colombian coffee extract (CE),
      which contains high concentrations of caffeine and diterpenoids, on a rat model
      of human metabolic syndrome. The 8-9 wk old male Wistar rats were divided into
      four groups. Two groups of rats were fed a corn starch-rich diet whereas the
      other two groups were given a high-carbohydrate, high-fat diet with 25% fructose
      in drinking water for 16 wk. One group fed each diet was supplemented with 5%
      aqueous CE for the final 8 wk of this protocol. The corn starch diet contained
      ~68% carbohydrates mainly as polysaccharides, whereas the high-carbohydrate, high
      fat diet contained ~68% carbohydrates mainly as fructose and sucrose together
      with 24% fat, mainly as saturated and monounsaturated fat from beef tallow. The
      high-carbohydrate, high-fat diet-fed rats showed the symptoms of metabolic
      syndrome leading to cardiovascular remodeling and nonalcoholic fatty liver
      disease. CE supplementation attenuated impairment in glucose tolerance,
      hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease
      without changing abdominal obesity and dyslipidemia. This study suggests that CE
      can attenuate diet-induced changes in the structure and function of the heart and
      the liver without changing the abdominal fat deposition.

PMID- 22378328
TI  - Growth in late infancy among HIV-exposed children in urban Haiti is associated
      with participation in a clinic-based infant feeding support intervention.
AB  - The integration of nutrition support for infants of HIV-infected mothers is a
      recognized need; however, the evidence for effective programmatic solutions is
      weak. The objective of our study was to implement and evaluate a new infant
      feeding support intervention for HIV-exposed, uninfected, non-breast-fed infants
      6-12 mo of age attending the Groupe Haitien d'Etude du Sarcome de Kaposi et des
      Infections Opportunistes (GHESKIO) pediatric clinic in Port-au-Prince, Haiti. The
      24-wk intervention included a lipid-based nutrient supplement, education,
      promotion of existing clinical services, and social support. We compared growth
      outcomes among intervention participants (n = 73) at start (wk 0) and end (wk 24)
      of intervention to a historical control group of HIV-exposed infants seen at the
      GHESKIO in the year prior to the intervention who would have met the intervention
      entrance criteria (n = 294). The intervention and historical control groups did
      not differ significantly at age 6 mo (wk 0). At age 12 mo (wk 24), the
      intervention group had a lower prevalence of underweight and stunting than the
      historical control group (weight-for-age Z-score < -2 SD: 6.8 vs. 20.8%, P =
      0.007; length-for-age Z-score < -2 SD: 9.6 vs. 21.2%, P = 0.029). Wasting tended
      to be lower in the intervention group than the historical control (weight-for
      length Z-score < -2 SD: 2.9 vs. 8.9%, P = 0.11). Implementation of the
      intervention was associated with reduced risk of growth faltering in HIV-exposed
      uninfected children from 6 to 12 mo of age. This is a promising intervention
      model that can be adapted and scaled-up to other HIV care contexts.

PMID- 22378329
TI  - Urinary enterolignan concentrations are positively associated with serum HDL
      cholesterol and negatively associated with serum triglycerides in U.S. adults.
AB  - Fiber-rich diets are associated with favorable lipid profiles, but the specific
      compounds and the mechanisms behind this effect are yet to be fully understood.
      Lignans are fiber-related polyphenols that have been associated with lower
      prevalence of cardiovascular disease. The objective of this study was to
      investigate the relationship between dietary lignan exposure, measured as the
      urinary concentration of their metabolites, enterolactone and enterodiol, and
      serum lipids in a representative sample of U.S. adults. We carried out a cross
      sectional analysis of data from 1492 adults who participated in the 1999-2004
      NHANES. The mean urinary concentration of enterolignans in U.S. adults was 1.9
      MUmol/L. The multivariate-adjusted mean differences comparing the highest and
      lowest enterolignan tertile were 0.06 mmol/L for HDL cholesterol and -0.17 mmol/L
      for TG (P < 0.05). In spline regression models, we also found an inverse
      association between serum TG and urinary enterolignan concentrations. Serum HDL
      cholesterol levels increased linearly with increasing enterolignan
      concentrations. Modest or no associations were found between enterolignan
      concentrations and serum LDL cholesterol or total cholesterol. In conclusion,
      enterolignan concentrations are associated with lower serum TG concentrations and
      greater HDL cholesterol concentrations in U.S. adults.

PMID- 22378330
TI  - Stunted child/overweight mother pairs represent a statistical artifact, not a
      distinct entity.
AB  - Stunted child/overweight mother (SCOWT) pairs have been viewed as a distinct
      phenomenon and much effort has been expended to characterize the environments
      that create these dual burden households. We hypothesized that the prevalence of
      SCOWT pairs is not independent of the prevalence of overweight mothers and
      stunted children in the general population. We analyzed data from the Demographic
      and Health Surveys (DHS) from 1991 to 2009. Datasets were included if the
      maternal BMI and the height-for-age Z-scores for children were reported. Mothers
      were included if they had a living child between 2 and 5 y old and were not
      currently pregnant. In 121 datasets from 54 countries, 339,202 households met the
      inclusion criteria. The median prevalences of maternal overweight, childhood
      stunting, and SCOWT pairs were 19.6% (range 1.6-70.7%), 27.3% (range 6.65-50.8%),
      and 3.3% (range 0.5-16.0%), respectively. The mean difference between the
      observed and expected prevalence of SCOWT pairs was -1.18% (95% CI -1.32%, 
      1.04%). Only two datasets had an observed prevalence of SCOWT pairs that was
      higher than the expected prevalence, but both were within the 95% CI for the
      observed prevalence. SCOWT prevalence was more strongly associated with maternal
      overweight than with child stunting. SCOWT pairs are not independent and their
      prevalence depends primarily on the prevalence of maternal overweight.

PMID- 22378331
TI  - Anterior cingulate taste activation predicts ad libitum intake of sweet and
      savory drinks in healthy, normal-weight men.
AB  - After food consumption, the motivation to eat (wanting) decreases and associated
      brain reward responses change. Wanting-related brain responses and how these are
      affected by consumption of specific foods are ill documented. Moreover, the
      predictive value of food-induced brain responses for subsequent consumption has
      not been assessed. We aimed to determine the effects of consumption of sweet and
      savory foods on taste activation in the brain and to assess how far taste
      activation can predict subsequent ad libitum intake. Fifteen healthy men (age: 27
      +/- 2 y, BMI: 22.0 +/- 1.5 kg/m2) participated in a randomized crossover trial.
      After a >3-h fast, participants were scanned with the use of functional MRI
      before and after consumption of a sweet or savory preload (0.35 L fruit or tomato
      juice) on two occasions. After the scans, the preload juice was consumed ad
      libitum. During scanning, participants tasted the juices and rated their
      pleasantness. Striatal taste activation decreased after juice consumption,
      independent of pleasantness. Sweet and savory taste activation were not
      differentially affected by consumption. Anterior cingulate taste activation
      predicted subsequent ad libitum intake of sweet (r = -0.78; P <
      0.001(uncorrected)) as well as savory juice (r = -0.70; P < 0.001(uncorrected)).
      In conclusion, we showed how taste activation of brain reward areas changes
      following food consumption. These changes may be associated with the food's
      physiological relevance. Further, the results suggest that anterior cingulate
      taste activation reflects food-specific satiety. This extends our understanding
      of the representation of food specific-appetite in the brain and shows that
      neuroimaging may provide objective and more accurate measures of food motivation
      than self-report measures.

PMID- 22378332
TI  - Traditional food intake is correlated with iron stores in Canadian Inuit men.
AB  - Accelerated loss of traditional lifestyles may place Inuit at risk of iron
      depletion given that anemia has been observed among Arctic men. The objectives of
      this study were to determine the prevalence of anemia, storage iron depletion,
      and iron overload and to identify correlates of iron status in Canadian Inuit
      men. In a cross-sectional survey of 994 men in the International Polar Year Inuit
      Health Survey, 2007-2008, hemoglobin, serum ferritin (SF), soluble transferrin
      receptor (on a subset), CRP, RBC fatty acid composition, and Helicobacter pylori
      serology were measured in venous blood drawn from fasting men. Anthropometric,
      dietary, sociodemographic, and health data were collected. Dietary and nondietary
      correlates of iron status were assessed with multiple linear and logistic models.
      For men with CRP <=10 mg/L (n = 804), 6.5% had depleted, 19.8% had low, and 10.3%
      had elevated iron stores. Anemia was moderately prevalent (16.1%), but iron
      deficiency anemia was less common (2.4%). There was a low probability of dietary
      iron inadequacy (2.4% < Estimated Average Requirement) and excess iron intakes
      (10.7% > Tolerable Upper Intake Level). Food-insecure men and those without a
      household hunter had a higher risk of low or depleted iron stores. Adiposity,
      traditional food intake, long-chain RBC PUFA status, and inflammation were
      positively associated with SF and food insecurity, smoking, and H. pylori
      seropositivity were negatively associated with SF. Despite a moderate prevalence
      of anemia, iron stores are largely adequate in this population, although lower
      than expected based on iron intake. The regulation of iron metabolism in this
      population and the high prevalence of anemia in older men warrants further
      investigation.

PMID- 22378333
TI  - Infant malnutrition is associated with persisting attention deficits in middle
      adulthood.
AB  - Infantile malnutrition is known to be associated with cognitive and behavioral
      impairment during childhood and adolescence. Data pertaining to longer-term
      effects on behavioral outcomes in adulthood are limited. In this study, we report
      associations between infantile malnutrition and attention problems in adults at
      midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales
      (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults
      (aged 37-43 y) who had been followed longitudinally since childhood. Previously
      malnourished participants (n = 80) had experienced moderate to severe protein
      energy malnutrition in the first year of life and were successfully rehabilitated
      thereafter. They were compared with healthy adults (n = 65) who were former
      classmates of the index cases and who had been matched for age, sex, and
      handedness in childhood. Multiple regression analyses showed persisting effects
      of childhood malnutrition on both the CAARS and the CPT, independent of effects
      of household standard of living assessed in childhood. The malnutrition effect on
      the CAARS ratings was independent of IQ, whereas this effect was attenuated for
      the CPT after adjustment for IQ. Teacher-reported attention problems in childhood
      predicted attention problems in adulthood, indicating continuity over the life
      span. Infantile malnutrition may have long-term effects on attentional processes
      nearly 40 y after the episode, even with excellent long-term nutritional
      rehabilitation and independent of socioeconomic conditions in childhood and
      adolescence. This finding has major public health implications for populations
      exposed to early childhood malnutrition.

PMID- 22378335
TI  - 1st Guidelines of the Brazilian Society of Cardiology on processes and skills for
      education in cardiology in Brazil--executive summary.
AB  - This article summarizes the "1st Guidelines of the Brazilian Society of
      Cardiology on Processes and Skills for Education in Cardiology in Brazil," which
      can be found in full at: <http://publicacoes.cardiol.br/consenso/2011/diretriz
      tec.asp>. The guideline establishes the education time required in Internal
      Medicine and Cardiology with Specialization through theoretical and practical
      training. These requirements must be available at the center forming Specialists
      in Cardiology and the Cardiology contents.

PMID- 22378334
TI  - The prevalence of stunting is high in HIV-1-exposed uninfected infants in Kenya.
AB  - As prevention of mother-to-child HIV-1 transmission (PMTCT) programs decrease the
      numbers of HIV-1-infected infants, it remains important to improve growth in HIV
      1-exposed, uninfected (EU) infants. To determine the growth rate and predictors
      of growth faltering in breast-fed and formula-fed EU infants, growth analyses
      [weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z
      scores] were conducted by using data from a randomized feeding trial in HIV-1
      infected women in Kenya. Growth faltering in EU infants was compared based on
      randomization to breastfeeding (BF) or formula feeding (FF) using Cox
      proportional hazards regression models. Linear mixed-effects models determined
      rate and cofactors of length growth. Among 338 EU infants, 164 (49%) were breast
      fed and 174 (51%) formula-fed. In both arms, growth declined steadily during
      follow-up. By 2 y, 29% of children were underweight (WAZ < -2), 18% were wasted
      (WLZ < -2), and 58% were stunted (LAZ < -2), with no differences by feeding arm.
      Higher maternal education (y) and taller stature (cm) were associated with a
      decreased risk of underweight and stunting [underweight: adjusted HR (aHR) = 0.90
      (95% CI: 0.83, 0.99), P = 0.03, and aHR = 0.92 (95% CI: 0.87, 0.97), P = 0.002;
      and stunting: aHR = 0.91 (95% CI: 0.85, 0.97), P = 0.003, and aHR = 0.96 (95% CI:
      0.92, 0.99), P = 0.02, respectively]. Diarrhea was associated with an increased
      risk of wasting [aHR = 2.26 (95% CI: 1.11, 4.62), P = 0.03]. In multivariate
      analyses, FF was associated with slower declines in length velocity [0.24 LAZ/y
      (95% CI: 0.06, 0.43), P = 0.009]. Despite being uninfected, HIV-1-exposed infants
      showed frequent growth faltering, suggesting the need for vigilance in
      recognizing stunting within PMTCT programs. The slower rate of decline in length
      growth with FF may reflect benefits of micronutrients. Because BF is the best
      option for HIV-1-infected mothers in resource-limited settings, nutritional
      interventions should be examined for their impact on growth in EU breast-fed
      infants.

PMID- 22378336
TI  - Mobilization of endothelial progenitor cells with exercise in healthy
      individuals: a systematic review.
AB  - Physical exercise mobilizes endothelial progenitor cells (EPCs) to peripheral
      blood. However, this effect seems to depend on exercise characteristics, such as
      duration and intensity. The aim of this systematic review was to verify the
      impact of a single bout of aerobic exercise on the mobilization of EPCs in
      healthy individuals, and the potential mechanisms involved. The bibliographic
      search was conducted on the following electronic databases in May 2011: SciELO,
      LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus and Medline. Of the 178
      articles initially identified, 12 met the inclusion criteria and were classified
      regarding quality according to the PEDro scale. The magnitude and duration of the
      EPC mobilization response were higher after long/ultralong duration exercises,
      and they are correlated with vascular endothelial growth factor (VEGF) plasma
      levels. The EPC mobilization peak in response to a maximal or submaximal single
      bout of exercise lasting up to one hour occurs immediately after the exercise or
      within the first hour after it. One possible mechanism is nitric oxide (NO)
      bioavailability. The individuals' age and exercise intensity seem to interfere
      with the EPC mobilization response. Long/ultralong duration exercises promote
      more pronounced EPC mobilization as compared with maximal or submaximal
      exercises. The mechanisms involve VEGF release in long/ultralong duration
      exercises and NO bioavailability in maximal or submaximal exercises lasting less
      than one hour.

PMID- 22378337
TI  - How to broaden the debate and utility of scientific communications: the open
      access journals.

PMID- 22378338
TI  - Case 2/2012--eleven-day-old infant with marked coarctation of the aorta in
      cardiogenic shock.

PMID- 22378339
TI  - Cardiovascular magnetic resonance in unsuspected interrupted inferior vena cava.
AB  - Interrupted inferior vena cava (IVC) is a rare anomaly. Anomalies of IVC are
      clinically important for cardiologists and radiologists who plan to intervene in
      the right heart. We describe three cases of IVC interruption diagnosed by cardiac
      magnetic resonance imaging study.

PMID- 22378340
TI  - Association between immunological diseases and their similar clinical
      manifestations.
AB  - We report on a 30-year-old female patient, with biological mitral valve
      prosthesis due to symptomatic mitral stenosis and a history of acute myocardial
      infarction and generalized tonic-clonic seizure episodes, visual hallucinations,
      cerebral thromboembolic events and, at present, chorea and acute carditis. The
      patient was diagnosed with active rheumatic fever (RF), systemic lupus
      erythematosus (SLE) and Antiphospholipid syndrome (APS). The combination of three
      unusual diagnoses in the same patient makes this a unique case, modifying patient
      treatment and prognosis.

PMID- 22378341
TI  - Peer review: a constantly-evolving scientific process.

PMID- 22378342
TI  - Advances in mechanical circulatory support in the treatment of heart failure.

PMID- 22378343
TI  - VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond.
AB  - Despite the enormous progress made in terms of prevention and early intervention,
      a pressing need remains to develop innovative therapeutic strategies for ischemic
      cardiovascular disorders, including acute myocardial infarction, chronic cardiac
      ischemia, peripheral artery disease and stroke. The induction of new blood vessel
      formation by delivering angiogenic genes to ischemic tissues continues to appear
      as a promising, alternative strategy to currently available therapies. In
      aspiring to induce therapeutic angiogenesis, the members of the vascular
      endothelial growth factor (VEGF) family have long been recognized as major
      molecular tools. Remarkably, VEGF family members have recently been recognized to
      also exert multiple, non-angiogenic effects on various cell types, including
      neurons, skeletal muscle and cardiac cells. Here, we critically review the VEGF
      based therapies that have already reached clinical experimentation and highlight
      the pleiotropic activities of VEGF factors that might create new opportunities
      for therapeutic application.

PMID- 22378344
TI  - Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated
      colitis in Cnlp(-/-) mice.
AB  - Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and
      immune cells. Whether endogenous cathelicidin is protective against ulcerative
      colitis, however, is unclear. Here we sought to delineate the role of endogenous
      murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal
      administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran
      sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp(-/-)) mice as a
      model. Cnlp(-/-) mice had more severe symptoms and mucosal disruption than the
      wild-type mice in response to DSS challenge. The tissue levels of interleukin
      1beta and tumor necrosis factor-alpha, myeloperoxidase activity and the number of
      apoptotic cells were increased in the colon of DSS-challenged Cnlp(-/-) mice.
      Moreover, mucus secretion and mucin gene expression were impaired in Cnlp(-/-)
      mice. All these abnormalities were reversed by the intrarectal administration of
      mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may
      protect against ulcerative colitis through modulation of inflammation and mucus
      secretion.

PMID- 22378345
TI  - Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating
      cardiomyocyte differentiation and function.
AB  - Engineered recombinant viral vectors are a powerful tool for vehiculating genetic
      information into mammalian cells. Because of their ability to infect both
      dividing and non-dividing cells with high efficiency, lentiviral vectors have
      gained particular interest for basic research and preclinical studies in the
      cardiovascular field. We review here the major applications for lentiviral-vector
      technology in the cardiovascular field: we will discuss their use in trailing
      gene expression during the induction of differentiation, in protocols for the
      isolation of cardiac cells and in the tracking of cardiac cells after
      transplantation in vivo; we will also describe lentivirally-mediated gene
      delivery uses, such as the induction of a phenotype of interest in a target cell
      or the treatment of cardiovascular diseases. In addition, a section of the review
      will be dedicated to reprogramming approaches, focusing attention on the
      generation of pluripotent stem cells and on transdifferentiation, two emerging
      strategies for the production of cardiac myocytes from human cells and for the
      investigation of human diseases. Finally, in order to give a perspective on their
      future clinical use we will critically discuss advantages and disadvantages of
      lentivirus-based strategies for the treatment of cardiovascular diseases.

PMID- 22378346
TI  - T cells redirected by a CD3zeta chimeric antigen receptor can establish self
      antigen-specific tumour protection in the long term.
AB  - A majority of cancer deaths are because of an uncontrolled relapse of the disease
      despite initial remission after therapy, asking for strategies to control tumour
      cells in the long term. Adoptive therapy with chimeric antigen receptor (CAR)
      redirected T cells showed promising success in primary tumour elimination; the
      capacity of such engineered T cells to establish enduring tumour protection is
      currently a matter of discussion, in particular as most targeted 'tumour
      associated antigens' are self-antigens. To address the issue in a clinically
      relevant model that closely mimics the human situation, we recorded rejection of
      carcinoembryonic antigen (CEA)-positive pancreatic tumours in the CEA transgenic
      mouse that expressed CEA as self-antigen in healthy cells of the gastrointestinal
      tract. Adoptive therapy with CD8(+) T cells, which were redirected by a CEA
      specific, low-affinity CAR with CD3zeta endodomain, eliminated CEA(+) tumours in
      a primary response; cured mice produced an efficient recall response in the long
      term towards CEA(+) tumour cells upon rechallenge. Secondary tumour rejection was
      CEA specific, mediated by engineered T cells and did not require host T cells. No
      toxicity towards healthy tissues with CEA expression was recorded. Data indicate
      that adoptive therapy with engineered T cells can establish self-antigen-specific
      tumour protection in the long term without autoimmunity.

PMID- 22378347
TI  - Non-classical membrane trafficking processes galore.
AB  - Dogmatic views of how proteins and other cellular components may traffic within
      and between eukaryotic cells have been challenged in the past few years. Beyond
      the classical secretory/exocytic pathway and its established players, other
      pathways of cell surface membrane transport, generally termed "unconventional
      secretion," are now better understood. More insights have also been gleaned on
      the roles of secreted or shedding microvesicles, either exosomal or ectosomal in
      origin, in unconventional secretion. Recent works have also revealed key
      molecular components, particularly the Golgi reassembly stacking protein (GRASP),
      and the importance of stress-induced autophagy, in unconventional exocytic
      transport. This GRASP and autophagy-dependent (GAD) mode appears to underlie the
      unconventional exocytosis of many soluble and membrane cargoes. Likewise, recent
      findings have revealed transport processes that contrast the classically known
      mitochondria import, namely vesicular transport from the mitochondria to
      peroxisomes and lysosomes. Mitochondria-peroxisomal targeting of mitochondria
      derived vesicles appears to involve the retromer complex, which was classically
      associated with endosome-Golgi membrane traffic. The routes of intracellular
      membrane transport and communications between eukaryotic organelles now appear
      far more complex that one would have imagined 10 years ago.

PMID- 22378348
TI  - Synthesis of C8-arylamine-modified 2'-deoxyadenosine phosphoramidites and their
      site-specific incorporation into oligonucleotides.
AB  - Adducts of C8-(N-acetyl)-arylamines and 2'-deoxyadenosine were synthesised by
      palladium-catalysed C--N cross-coupling chemistry. These 2'-dA adducts were
      converted into the corresponding 3'-phosphoramidites and site-specifically
      incorporated into DNA oligonucleotides, which were characterised by mass
      spectrometry, UV thermal-stability assays and circular dichroism. These modified
      oligonucleotides were also used in EcoRI restriction assays and in primer
      extension studies with three different DNA polymerases. The incorporation of the
      2'-dA lesion close to the EcoRI restriction site dramatically reduced the
      susceptibility of the DNA strand to cleavage; this indicates a significant local
      distortion of the DNA double helix. The incorporation of the acetylated C8-2'-dA
      phosphoramidites into 20-mer oligonucleotides failed, however, because the N
      acetyl group was lost during the deprotection process. Instead the corresponding
      C8-NH-2'-dA-modified oligonucleotides were obtained. The effect of the C8-NH
      arylamine-dA lesion on the replication by DNA polymerases was clearly dependent
      both on the polymerase used and on the arylamine-dA damage.

PMID- 22378349
TI  - Low high-density lipoprotein cholesterol is not responsible for decreased
      paraoxonase activity in chronic renal failure.
AB  - BACKGROUND/AIMS: Human paraoxonase-1 (PON1) is responsible for the antioxidant
      effect of high-density lipoprotein (HDL) by inhibiting low-density lipoprotein
      oxidation. Previous studies discovered dyslipidemia (DL) and decreased PON1
      activity in chronic renal failure (CRF). We aimed to determine PON and
      arylesterase activity, phenotypic distribution of the PON1 enzyme, and lipid
      profile in low and normal HDL cholesterol (HDL-C) patients with CRF, and renal
      transplant (TX), compared to primary DL. METHODS: 116 CRF (low or normal HDL-C),
      52 TX (low or normal HDL-C), and 62 DL patients (low or normal HDL-C) were
      included. PON and arylesterase activities were measured spectrophotometrically.
      Phenotype was determined using the dual substrate method. RESULTS: Aryl/HDL-C was
      significantly higher in low HDL-C patients. Patients with CRF had significantly
      lower arylesterase activity compared to DL, independent of HDL-C. PON activity
      and PON/HDL-C did not differ significantly in CRF compared to TX and DL.
      Phenotypic distribution was similar in patient groups. Low HDL-C CRF patients had
      significantly lower cholesterol and triglyceride than DL. CONCLUSION: Decreased
      arylesterase activity, correlating with PON1 enzyme protein quantity, is not
      explicable by decreased HDL-C in CRF. Low HDL-C CRF patients' increased
      cardiovascular morbidity is not attributable to changes in PON1 activity, or
      phenotypic distribution.

PMID- 22378350
TI  - Atherothrombotic burden and medium-term prognosis in patients with acute ischemic
      stroke: findings of the SIRIO study.
AB  - BACKGROUND: Short- and medium-term mortality after acute stroke is related to the
      severity of the index event and the patient's age. However, recent studies have
      reassessed the prognostic value of the systemic atherothrombotic burden in these
      patients, not only in the long term. This post hoc analysis of the findings of
      the SIRIO trial (Stroke in Italy and Related Impact on Outcome) examined the
      prognostic impact of systemic atherothrombosis. METHODS: SIRIO was a multicenter
      observational study enrolling patients during the acute phase of stroke of both
      ischemic and hemorrhagic origin. The present analysis, however, only covered
      patients with ischemic stroke. At baseline, the main personal and clinical
      details were recorded and patients were classified as having either polyvascular
      disease or single arterial disease on the basis of whether they had symptomatic
      atherothrombotic disease in other sites besides the cerebrovascular location. For
      all patients we calculated the Essen Stroke Risk Score (ESRS), dividing them into
      groups with scores of less than 3 or 3 and more. We recorded total mortality and
      nonfatal vascular events 12 months after enrolment. Multivariate logistic
      regression analysis was used to select predictors of medium-term mortality and
      nonfatal cardiovascular events. There were 2,561 patients with ischemic stroke,
      823 of them classified as having polyvascular disease; 940 (out of 2,485) had an
      ESRS of less than 3 and 1,545 had a score of 3 or more. RESULTS: The combined
      endpoint 'death (all causes) and nonfatal cardiovascular events within 12 months
      of hospital discharge' was significantly dependent on the following factors:
      ESRS, Rankin scale and National Institutes of Health Stroke Scale scores, and
      polyvascular disease. Polyvascular disease status significantly affected
      mortality and nonfatal cardio- and cerebrovascular events after discharge (OR =
      1.44, 95% CI = 1.10-1.88). Age was also confirmed as a significant predictor of
      the combined endpoint. CONCLUSIONS: Besides age and the clinical severity of the
      index event, symptomatic involvement of several vascular districts was also an
      important predictor of mortality and nonfatal cardiovascular events in the medium
      term in patients with ischemic stroke.

PMID- 22378351
TI  - Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration
      and invasion and is directly regulated by tumor-suppressive microRNA-133a in head
      and neck squamous cell carcinoma.
AB  - Our expression signatures of human cancers including head and neck squamous cell
      carcinoma (HNSCC) demonstrated that downregulation of microRNA-133a (miR-133a)
      were frequently observed in cancer cells. The restoration of miR-133a in cancer
      cells revealed that it functions as a tumor suppressor. In this study, we
      investigated the novel molecular targets of miR-133a in HNSCC cancer cells and
      its oncogenic function, especially as it contributes to cancer cell migration and
      invasion. The genome-wide gene expression analysis and bioinformatics study
      showed that actin-related protein 2/3 complex subunit 5 (ARPC5) is a candidate
      target of miR-133a. Furthermore, luciferase reporter assay demonstrated that
      ARPC5 is directly regulated by miR-133a. Silencing of ARPC5 revealed significant
      inhibition of cell migration and invasion in HNSCC cell lines, SAS, HSC3 and IMC
      3. In HSC3 cells, restoration of miR-133a or silencing ARPC5 led to a
      reorganization of the actin cytoskeleton and a subsequent change in cell
      morphology to a round, bleb-like shape. The expression levels of ARPC5 were
      significantly higher in HNSCC tissues than in non-cancer tissues.
      Immunohistochemistry showed that the levels of ARPC5 expression were
      significantly higher in invasive cancer cells. ARPC5 contributed to cancer cell
      migration and invasion in HNSCC and this gene was directly regulated by miR-133a.
      Our analysis of novel tumor-suppressive miR-133a-mediated cancer pathways
      provides new insights into the potential mechanisms of HNSCC oncogenesis.

PMID- 22378352
TI  - A phthalocyanine-peptide conjugate with high in vitro photodynamic activity and
      enhanced in vivo tumor-retention property.
AB  - A novel zinc(II) phthalocyanine conjugated with a short peptide with a nuclear
      localization sequence, Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val, was synthesized by
      click chemistry and a standard Fmoc solid-phase peptide synthesis protocol. The
      conjugate was purified by HPLC and characterized with UV/Vis and high-resolution
      mass spectroscopic methods. Both this compound and its non-peptide-conjugated
      analogue are essentially non-aggregated in N,N-dimethylformamide and can generate
      singlet oxygen effectively with quantum yields (Phi(Delta)) of 0.84 and 0.81,
      respectively, relative to unsubstituted zinc(II) phthalocyanine (Phi(Delta)
      =0.56). Conjugation of the peptide sequence, however, can enhance the cellular
      uptake, efficiency in generating intracellular reactive oxygen species, and
      photocytotoxicity of the phthalocyanine-based photosensitizer against HT29 human
      colorectal carcinoma cells. The IC(50) value of the conjugate is as low as 0.21
      MUM. In addition, the conjugate shows an enhanced tumor-retention property in
      tumor-bearing nude mice. After 72 h post-injection, the dye concentration in the
      tumor was significantly higher than that in other organs. The results suggest
      that this phthalocyanine-peptide conjugate is a highly promising photosensitizer
      for photodynamic therapy.

PMID- 22378354
TI  - Prognostic nomogram for disease-free survival in patients with renal
      adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to develop a postoperative prognostic
      nomogram for disease-free survival in patients with renal adenocarcinoma.
      MATERIALS AND METHODS: A total of 224 patients with organ-confined or locally
      advanced renal adenocarcinoma were treated with radical or partial nephrectomy.
      The variables included in the model were age, histological type, pathological
      stage, Fuhrman grade and DNA ploidy. Tumor recurrence was defined as any clinical
      evidence of recurrence. The probability of progression-free survival was
      calculated using the Kaplan-Meier estimate, and multivariate analysis was
      performed using a Cox regression. The nomogram was created using the data
      obtained from the Cox regression. RESULTS: Tumor recurrence was detected in 89
      patients (39.74%). The median progression-free time in these patients was 9.55
      months (range 0-133). Of these patients, 70.9% relapsed during the first 2 years,
      and only 15 patients (6.9%) were alive but ill at the end of the study. The
      probability of progression-free survival at 5 and 10 years was 66.64 and 61.97%,
      respectively. We performed a statistical validation of the model with accurate
      predictions that were discriminated with a confidence interval of 0.75 (comparing
      the predicted and actual probability). According to the nomogram obtained,
      patients with low-grade, diploid, organ-confined tumors would be candidates for
      follow-up not exceeding 5 years due to the low probability of recurrence (<40
      points). CONCLUSION: The nomogram we developed is clinically relevant and can
      provide prognostic information for both patients and researchers. In addition, it
      can be used by researchers during the monitoring protocols that categorize
      patients based on their relative risk of disease progression.

PMID- 22378355
TI  - Performance of dispersion-corrected density functional theory for the
      interactions in ionic liquids.
AB  - Potential energy curves for the dissociation of cation-anion associates
      representing the building units of ionic liquids have been computed with
      dispersion corrected DFT methods. Non-local van der Waals density functionals
      (DFT-NL) for the first time as well as an atom pair-wise correction method (DFT
      D3) have been tested. Reference data have been computed at the extrapolated
      MP2/CBS and estimated CCSD(T)/CBS levels of theory. The investigated systems are
      combined from two cations (1-butyl-3-methylimidazolium and
      tributyl(methyl)posphonium) and three anions (chloride, dicyanamide, acetate). We
      find substantial stabilization from London dispersion energy near equilibrium of
      5-7 kcal mol(-1) (about 5-6% of the interaction energy). Equilibrium distances
      are shortened by 0.03-0.09 A and fundamental (inter-fragment) vibrational
      frequencies (which are in the range 140-180 cm(-1)) are increased by typically 10
      cm(-1) when dispersion corrections are made. The dispersion-corrected hybrid
      functional potentials are in general in excellent agreement with the
      corresponding CCSD(T) reference data (typical deviations of about 1-2%). The DFT
      D3 method performs unexpectedly well presumably because of cancellation of errors
      between the dispersion coefficients of the cations and anions. Due to self
      interaction error, semi-local density functionals exhibit severe SCF convergence
      problems, and provide artificial charge-transfer and inaccurate interaction
      energies for larger inter-fragment distances. Although these problems may be
      alleviated in condensed phase simulations by effective Coulomb screening, only
      dispersion-corrected hybrid functionals with larger amounts of Fock-exchange can
      in general be recommended for such ionic systems.

PMID- 22378357
TI  - Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata
      ssp. sesquipedialis) germplasm: implications for domestication history and genome
      wide association studies.
AB  - Association mapping of important traits of crop plants relies on first
      understanding the extent and patterns of linkage disequilibrium (LD) in the
      particular germplasm being investigated. We characterize here the genetic
      diversity, population structure and genome wide LD patterns in a set of asparagus
      bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse
      collection of 99 asparagus bean and normal cowpea accessions were genotyped with
      1127 expressed sequence tag-derived single nucleotide polymorphism markers
      (SNPs). The proportion of polymorphic SNPs across the collection was relatively
      low (39%), with an average number of SNPs per locus of 1.33. Bayesian population
      structure analysis indicated two subdivisions within the collection sampled that
      generally represented the 'standard vegetable' type (subgroup SV) and the 'non
      standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was
      higher and extent of LD persisted longer in subgroup SV than in subgroup NSV,
      whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied
      among chromosomes, with the longest (~ 5 cM) five times longer than the shortest
      (~ 1 cM). Partitioning of LD variance into within- and between-subgroup
      components coupled with comparative LD decay analysis suggested that linkage
      group 5, 7 and 10 may have undergone the most intensive epistatic selection
      toward traits favorable for vegetable use. This work provides a first population
      genetic insight into domestication history of asparagus bean and demonstrates the
      feasibility of mapping complex traits by genome wide association study in
      asparagus bean using a currently available cowpea SNPs marker platform.

PMID- 22378358
TI  - Hearing echoes.

PMID- 22378356
TI  - Overweight and obesity among North American Indian infants, children, and youth.
AB  - The frequency of overweight and obesity among North American Indian children and
      youth exceeds that of other ethnic groups in the United States. This observation
      is based on studies using body mass index as the primary measure of overweight
      and obesity. In the mid-20th century, there were regional differences among North
      American Indian groups in sub-adults' size and shape and only a few Southwestern
      groups were characterized by high rates of overweight and obesity. In most
      populations, the high prevalence of overweight and obesity developed in the last
      decades of the 20th century. Childhood obesity may begin early in life as many
      studies report higher birth weights and greater weight-for-height in the
      preschool years. Contributing factors include higher maternal weights, a
      nutritional transition from locally caught or raised foods to store bought items,
      psychosocial stress associated with threats to cultural identity and national
      sovereignty, and exposure to obesogenic pollutants, all associated to some degree
      with poverty. Obesity is part of the profile of poor health among Native
      Americans in the US and Canada, and contributes to woefully high rates of
      diabetes, cardiovascular disease, and early mortality. Interventions that are
      culturally appropriate are needed to reduce weights at all points in the
      lifespan.

PMID- 22378359
TI  - Butterfly wing colours are driven by the evolution of developmental heterochrony.
      Butterfly wing colours and patterning by numbers.

PMID- 22378360
TI  - Novel G protein-coupled oestrogen receptor GPR30 shows changes in mRNA expression
      in the rat brain over the oestrous cycle.
AB  - Oestrogen influences autonomic function via actions at classical nuclear
      oestrogen receptors alpha and beta in the brain, and recent evidence suggests the
      orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic
      oestrogen receptor. We investigated the expression of GPR30 in female rat brains
      throughout the oestrous cycle and after ovariectomy to determine whether GPR30
      expression in central autonomic nuclei is correlated with circulating oestrogen
      levels. In the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM)
      and periaqueductal gray (PAG) GPR30 mRNA, quantified by real-time PCR, was
      increased in proestrus and oestrus. In ovariectomised (OVX) rats, expression in
      NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic
      paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like
      immunoreactivity (GPR30-LI) colocalised with Golgi in neurones in many brain
      areas associated with autonomic pathways, and analysis of numbers of
      immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI
      was found in a variety of transmitter phenotypes, including cholinergic,
      serotonergic, catecholaminergic and nitrergic neurones in different neuronal
      groups. These observations support the view that GPR30 could act as a rapid
      transducer responding to oestrogen levels and thus modulate the activity of
      central autonomic pathways.

PMID- 22378361
TI  - Tailoring a stabilized variant of hydroxynitrile lyase from Arabidopsis thaliana.
AB  - The R-selective hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) cannot be
      applied for stereoselective cyanohydrin syntheses in aqueous media because of its
      limited stability at pH<5, which is required in order to suppress the uncatalyzed
      racemic cyanohydrin formation. To stabilize AtHNL we designed a surface-modified
      variant incorporating 11 changes in the amino acids on the protein surface.
      Comparative characterization of the variant and the wild-type enzyme showed a
      broadened pH optimum towards the acidic range, along with enhancement of activity
      by up to twofold and significantly increased pH- and thermostabilities. The
      effect can most probably be explained by a shift of the isoelectic point from pH
      5.1 to 4.8. Application of the variant for the synthesis of (R)-cyanohydrins in
      an aqueous/organic two-phase system at pH 4.5 demonstrated the high
      stereoselectivity and robustness of the variant relative to the wild-type enzyme,
      which is immediately inactivated under these conditions.

PMID- 22378362
TI  - Long-term following-up of viability of spleen autotransplants in the Beagle
      canine model.
AB  - PURPOSE: To examine the possible late complications of splenectomy or spleen
      autotransplantation in large laboratory animal model, in which we need non
      invasive or minimal-invasive methods for long-term monitoring of the experimental
      animals. METHODS: Experimental groups of beagle dogs were: non-operated control,
      sham-operated control, splenectomy, spleen autotransplantation with 5 or 10
      spleen-chips taken into the greater omentum (Furka's technique). Prior to
      operations, on the 1(st) postoperative week, monthly till the 6(th) as well as in
      the 9(th) and 12(th) month, hemorheological examinations were performed. In
      postoperative 12(th) month colloid scintigraphy and diagnostic laparoscopy were
      carried out. At the end of the investigation comparative morphological
      examinations were performed, too. RESULTS: From the 4(th)-5(th) postoperative
      month filtration function of spleen-autotransplants showed particular restoration
      compared to splenectomy group. However, the functional results did not reach the
      values of the control or sham-operated groups. Sham-operated control's
      scintigraphy nicely showed activity in the spleen. In spleen autotransplantation
      groups scintigraphy indicated well the activity of spleen-chips. During
      diagnostic laparoscopy spleen-chips with their blood supply were found.
      Histologically, the structure of spleen-autotransplants was similar to normal
      splenic tissue. CONCLUSIONS: The autotransplants are regenerated, their functions
      have been partly restored, and thus spleen autotransplantation may prevent the
      possible complications of splenectomy. These parameters and the presented
      investigative protocol are suitable for long-term following-up of viability of
      the spleen-autotransplants.

PMID- 22378363
TI  - Experimental canine model for sentinel lymph node biopsy in the vulva using
      technetium and patent blue dye.
AB  - PURPOSE: This paper aims to study and define the experimental model of sentinel
      lymph node biopsy of the vulva in bitches. METHODS: 0.2 ml of 99mTc phytate was
      injected intradermally, using a fine gauge insulin needle in the anterior
      commissure of the vulva. Thirty minutes after 99mTc injection, the inguinal
      mapping was performed using a gamma probe. After this, 0.5 ml of blue dye (bleu
      patente V Guerbet 2.5%) was injected in the same place. After 15 minutes, a 3 cm
      long inguinal incision was made at point maximum uptake followed by careful
      dissection, guided by visualization of a bluish afferent lymphatic system that
      points to the sentinel lymph node (SLN). RESULTS: It was observed that 88% of SLN
      were identified. It wasn't found a significant difference among the presence or
      not of sentinel lymph node in the sides, which is an indication of a good
      consistency. It was observed a high (88%) and significant (chi2=12.89 and
      p=0.0003) intercession between both methods (blue dye and radiation). CONCLUSION:
      The experimental model adopted is feasible, becoming advantageous in applying the
      association of Patent blue and 99mTc.

PMID- 22378364
TI  - Effects of controlled and pressure support mechanical ventilation on rat
      diaphragm muscle.
AB  - PURPOSE: The objective of this study was to analyze the effects of Pressure
      Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats.
      METHODS: Wistar rats (n=18) were randomly assigned to the control group or to
      receive 6 hours of PCV and PSV. After this period, animals were euthanized and
      their diaphragms were excised, frozen in liquid nitrogen and stored in at -80o C
      for further histomorphometric analysis. RESULTS: Results showed a 15% decrease in
      cross-sectional area of muscle fibers on the PCV-C group when compared to the
      control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor
      diameter was decreased in PCV-C group by 9% when compared with the control group
      (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area
      was analyzed, a 16% decrease was observed in the PCV-C group when compared to the
      PSV group (p<0.05). No significant difference between the groups was observed in
      myonuclear perimeter (p>0.05). CONCLUSION: Short-term controlled mechanical
      ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode
      may attenuate the effects of VIDD.

PMID- 22378365
TI  - Low-level laser on femoral growth plate in rats.
AB  - PURPOSE: To determine the influence of low-level laser therapy on femoral growth
      plate in rats. METHODS: Thirty male Wistar rats aged 40 days were divided into
      two groups, G1 and G2. In G1 the area of the distal growth plate of the right
      femur was irradiated at one point using GaAlAs laser 830 nm wavelength, output
      power of 40 mW, at an energy density of 10 J/cm(2). The irradiation was performed
      daily for a maximum of 21 days. The same procedure was done in G2, but the probe
      was turned off. Five animals in each group were euthanized on days 7, 14 and 21
      and submitted to histomorphometric analysis. RESULTS: In both groups the growth
      plate was radiographically visible at all moments from both craniocaudal and
      mediolateral views. On the 21st day percentage of femoral longitudinal length was
      higher in G2 than G1 compared to basal value while hypertrophic zone chondrocyte
      numbers were higher in G1 than G2. Calcified cartilage zone was greater in G1
      than in G2 at all evaluation moments. Angiogenesis was higher in G1 than in G2 at
      14th and 21st days. CONCLUSION: The low-level laser therapy negatively influenced
      the distal femoral growth plate.

PMID- 22378366
TI  - Clinical and nutritional status in the late postoperative of
      pancreaticoduodenectomy: influence of pylorus preservation procedure.
AB  - PURPOSE: To evaluate the nutritional status of patients in the late postoperative
      period of pancreaticoduodenectomy (PD) and compare the long-term outcome
      according to pylorus-preserving (PPPD) or the standard technique (SPD) in which
      the pylorus is resected. METHODS: This prospective study was conducted twelve
      months prior or more in patients who had underwent PD (PD Group, n=15) and health
      volunteers (Control Group, n=15). At a post hoc analysis, the PD Group was
      divided in PPPD Subgroup (n=9) and SPD Subgroup (n=6), according to the PD
      techniques. Gastrointestinal complaints and nutritional status were evaluated,
      apart from a biochemical assessment; Student t-test or Mann-Whitney test were
      used. RESULTS: The patients recovered their body weight and the gastrointestinal
      complaints were uncommon. The PD Group showed higher energy and protein intake
      even though BMI was lower than in Control Group. There were no differences in
      laboratorial data, except for higher glycemia, serum alkaline phosfatase and C
      reactive protein in PD Group. There was no difference in the various parameters
      evaluated when the Subgroups (PPPD and SPD) were compared. CONCLUSION: For long
      term pancreaticoduodenectomy, the gastrointestinal symptoms are minimal and the
      patients had the clinical and nutritional status preserved, regardless of pylorus
      preservation.

PMID- 22378367
TI  - Diclofenac sodium and Imipenem action on rat intestinal mucosa: a biomechanical
      and histological study.
AB  - PURPOSE: To study diclofenac sodium induced histological and mechanical
      alterations and their prevention with Imipenem in rat intestine. METHODS: Male
      Wistar rats (n=240) were randomly assigned to four experimental groups: GI: n=60
      treated with 0.9% saline IM; GII: n=60 treated with 6 mg/kg body weight
      diclofenac sodium IM for four days; GIII: n=60 treated with 30 mg/kg body weight
      Imipenem IM for four days, and GIV n=60 treated with diclofenac sodium plus
      Imipenem at the above doses IM for 4 days. Each group was further divided into 4
      subgroups of 15 rats each and sacrificed at 4, 7, 14, and 21 days of follow-up,
      respectively. Abdominal cavity macroscopy and histology, and small bowel breaking
      strength were analyzed at each sacrifice moment. RESULTS: There were no
      histological or mechanical alterations in normal control rats throughout the
      study. Ulcerated lesions in intestinal mucosa were observed and breaking strength
      decreased in all diclofenac sodium treated rats. Ulcerated lesions in intestinal
      mucosa were prevented by Imipenem in all rats. CONCLUSION: Diclofenac sodium
      induced ulcerated lesions in rat intestinal mucosa can be prevented by Imipenem
      treatment.

PMID- 22378368
TI  - Lumbosacral epidural magnesium prolongs ketamine analgesia in conscious sheep.
AB  - PURPOSE: To determine the analgesic, motor, sedation and systemic effects of
      lumbosacral epidural magnesium sulphate added to ketamine in the sheep. METHODS:
      Six healthy adult male mixed-breed sheep; weighing 43 +/- 5 kg and aged 20-36
      months. Each sheep underwent three treatments, at least 2 weeks apart, via
      epidural injection: (1) ketamine (KE; 2.5 mg/kg), (2) magnesium sulphate (MG; 100
      mg), and (3) KE + MG (KEMG; 2.5 mg/kg + 100 mg, respectively). Epidural
      injections were administered through the lumbosacral space. Analgesia, motor
      block, sedation, cardiovascular effects, respiratory rate, skin temperature, and
      rectal temperature were evaluated before (baseline) and after drug administration
      as needed. RESULTS: The duration of analgesia with the lumbosacral epidural KEMG
      combination was 115 +/- 17 min (mean +/- SD), that is, more than twice that
      obtained with KE (41 +/- 7 min) or MG (29 +/- 5 min) alone. KE and KEMG used in
      this experiment induced severe ataxia. The heart rate and arterial blood
      pressures changes were no statistical difference in these clinically health
      sheep. CONCLUSION: The dose of magnesium sulphate to lumbosacral epidural
      ketamine in sheep is feasible, and can be used in procedures analgesics in sheep.

PMID- 22378369
TI  - Association of midazolam with ketamine in giant Amazon river turtles Podocnemis
      expansa breed in captivity.
AB  - PURPOSE: Evaluate the effects of two anesthetic associations in giant Amazon
      river turtles (P. expansa). METHODS: Twenty P. expansa, healthy, of both sexes,
      with weights between 1.0 and 1.5 kg of a commercial breeding facility located in
      the valley of the Araguaia River, Goias, Brazil, were divided into two groups (
      G1 n = 10 and G2 n = 10). Each group received a protocol being: P1 = midazolam (2
      mg/kg IM) and ketamine (20 mg/kg IM) and P2 = midazolam (2 mg/kg IM) and ketamine
      (60 mg/kg IM), applied on G1 and G2, respectively. The drugs were applied in the
      left forelimb. The clinical parameters evaluated were: locomotion, muscle
      relaxation, response to pain stimuli in the right thoracic and pelvic members and
      heart rate. These assessments were made at time 0 (immediately after injection)
      and times of 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes after the
      injections. RESULTS: Group 2 showed a higher heart rate than G1 and more rapid
      and prolonged immobilization. CONCLUSION: The sedation scores obtained by these
      protocols (P1 and P2) were satisfactory, with possible pharmacological contention
      for collecting biological samples and physical examination in P. expansa.

PMID- 22378370
TI  - Value of color Doppler ultrasonography and radiography for the assessment of the
      cancellous bone scaffold coated with nano-hydroxyapatite in repair of radial bone
      in rabbit.
AB  - PURPOSE: To evaluate the osteo-regenerative capacity of proprietary bone grafting
      material as a bone defect filler and osteogenetic stimulation to speed up bone
      healing too. METHODS: Eighteen adult male New Zealand white rabbits were
      anesthetized and a segmental full thickness bone defect of 10 mm in length was
      created in the middle of the right radial shaft in all rabbits. They were divided
      into two groups of 9 rabbits. Group I was considered as control and the fractured
      site was fixed using finger bone plate with 4 screws, whereas the cancellous bone
      scaffold coated with Nano-Hydroxyapatite was used to fill the gap after fracture
      fixation in Group II. Radiography, two dimensional and color Doppler
      ultrasonography were done before and after creating defects and on 0, 15, 30, 60
      and 90 days to evaluate local reaction as far as new blood vessels network and
      callus formation are observed. RESULTS: On the radiographs during the whole
      process, bone repair in Group I was not as perfect as those in Group II samples
      and trace of internal callus filled the gap incompletely in 60 days in Group I,
      whereas in Group II internal callus almost was formed on 30 days and in addition
      intercortical callus was seen supporting to cover and filled the gap completely
      in this group in 60 day; Sonographic findings confirmed the protrusion of newly
      formed blood vascular network in 30 days in Group I and from 15 days in Group II
      and remarkably increased till end of observation period. CONCLUSIONS: The nano
      hydroxyapatite with more features and shorter in time, made possible the
      reconstruction of bone tissue and alternative techniques as well as previous bone
      graft, also radiography and ultrasonography are reliable techniques to trace
      local reaction at proper time.

PMID- 22378371
TI  - The effects of different doses of 670 nm diode laser on skin flap survival in
      rats.
AB  - PURPOSE: To investigate the effects of different low-level laser therapy (LLLT)
      doses on random skin flap rats. METHODS: Forty Wistar rats were randomly divided
      in four groups. The control group (CG) was not irradiated. The experimental
      groups were irradiated with a diode laser 670 nm with different energies per
      point: group 2 (G2) with 0.06 J; group 3 (G3) 0.15 J and group 4 (G4) 0.57 J. The
      three groups were irradiated in 12 equally distributed points in the cranial skin
      flap portion. They were submitted to the irradiation during the immediate, first
      and second postoperative days. The necrosis area was evaluated in the seventh
      postoperative day. RESULTS: The CG shows 49.35% of necrosis area in the skin
      flap; G2, 39.14%; G3, 47.01% and G4, 29.17% respectively. There was a
      significantly difference when G4 was compared with CG's skin flap necrosis area.
      CONCLUSION: The low-level laser therapy diode 670 nm with 0.57 J energy per point
      increases the survival in randomic skin flap rats.

PMID- 22378372
TI  - Histology of the rectus abdominis muscle in rats subjected to cranial and caudal
      devascularization.
AB  - PURPOSE: To investigate the microscopic changes in the rectus abdominis muscle in
      rats subjected to five delay procedure. METHODS: 30 male Holtzmann rats,
      weighting between 250 and 350 grams, were used. The animals were divided into
      five groups (n=6): A - cranial section of the right muscle; B - caudal section of
      the right muscle; C - craniocaudal section of the right muscle; D - cranial
      section reflecting the right muscle in the craniocaudal direction; E - caudal
      section reflecting the right muscle in the caudocranial direction. On the seventh
      day after surgery, a resection of the cranial and caudal fragments of the right
      and left muscles, respectively, was performed for microscopic analysis.
      Histological alterations were quantified and the right and left (control) muscle
      fragments compared. Fisher's exact test was used for statistical purposes with a
      significance level of 5%. RESULTS: The comparison between right and left muscles
      showed statistically significant differences in group A - inflammatory infiltrate
      in the cranial fragment (p=0.015); in group C - inflammatory infiltrate (p=0.000)
      and necrosis (p=0.015) in the caudal fragment; and in group E - edema in the
      caudal fragment (p=0.000). No significant alterations were noted in groups B and
      D. CONCLUSIONS: Irrigation exclusively through the perforating muscle vessels is
      inappropriate; irrigation exclusively through the cranial pedicle causes milder,
      insignificant histological alterations, when compared with irrigation exclusively
      through the caudal pedicle; irrigation exclusively through the caudal pedicle
      causes more pronounced, but still insignificant, histological alterations when
      compared with other forms of devascularization.

PMID- 22378374
TI  - Propofol effects on the morphology of rat testes subjected to testicular ischemia
      reperfusion.
AB  - PURPOSE: To evaluate the effects of propofol as an inhibitor of tissue injury in
      testicular ischemia-reperfusion in rats. METHODS: 30 Wistar rats were assigned to
      one of three groups of 10 animals: G1, testicular exposure alone; G2 and G3:
      testicular ischemia caused by left spermatic cord torsion of 720o. In G3,
      propofol was administered intraperitoneally at 20 mg/kg/h 45 minutes after
      spermatic cord torsion. In G2 and G3, spermatic cords were detorsioned after 60
      min. In all three groups, testes were subsequently repositioned in the scrotum.
      After 90 days, bilateral orchiectomy was performed for histological examination.
      RESULTS: No abnormalities in seminiferous tubules were found in G1. In G2, 86.6%
      of left testes exhibited abnormalities, in contrast with 67.8% for right testes.
      In G3, these proportions were 57.3% and 45.6%, respectively. A statistically
      significant difference was found between G2 and G3. CONCLUSION: Propofol reduced
      the tissue damage in rat testes subjected to ischemia-reperfusion caused by
      spermatic cord torsion.

PMID- 22378373
TI  - Effect of N-acetylcysteine on lung injury induced by skeletal muscle ischemia
      reperfusion. Histopathlogical study in rat model.
AB  - PURPOSE: To investigate whether N-acetylcysteine, a free radicals scavenger has a
      protective effect against lung injury as a remote organ after skeletal muscle
      ischemia-reperfusion. METHODS: Twenty Wistar male rats were divided randomly into
      two experimental groups: group ischemia-reperfusion (group I) and group ischemia
      reperfusion +N-acetylcysteine (group II). All animals were undergone two hours of
      ischemia by occlusion femoral artery and 24h of reperfusion. Before clamped the
      femoral artery, 250 IU heparin was administered via the jugular vein to prevent
      clotting. Rats that were treated with N-acetylcysteine given IV at a dose of 150
      mgkg(-1), immediately before reperfusion. After 24h of reperfusion, animals were
      euthanized and left lung harvested for histopathological analysis under light
      microscopy. RESULTS: In the group I, tissues showed histological changes with
      intra-alveolar edema, intra-alveolar hemorrhage and neutrophilic infiltration.
      Histopathologically, there was a significant difference (P = 0.005) between two
      groups. CONCLUSION: Administration of N-acetylcysteine treatment significantly
      decreased lung injury induced by skeletal muscle ischemia reperfusion according
      to histological findings.

PMID- 22378375
TI  - Changes in morphology of long bone marrow tissue of rats submitted to cryotherapy
      with liquid nitrogen.
AB  - PURPOSE: To study the main effects of local use of liquid nitrogen on bone marrow
      tissue in rats. METHODS: The femoral diaphyses of 42 Wistar rats were exposed to
      three local and sequential applications of liquid nitrogen for one or two
      minutes, intercalated with periods of five minutes of passive thawing. The
      animals were sacrificed after one, two, four and 12 weeks and the specimens
      obtained were analyzed histomorphologically. RESULTS: In the second experimental
      week of one-minute protocol, histological degree of inflammation obtained a mean
      score of one (mild), ranging from 0 (absent or scarce) and two (moderate)
      (Kruskal-Wallis test p=0.01). In the second experimental week of two-minute
      protocol, degree of inflammation to the medullar tissue obtained an average score
      of two (Kruskal-Wallis test p=0.01). CONCLUSION: The degree of inflammation of
      the bone marrow tissue was higher in protocol of three applications of two
      minutes compared to protocol of three applications of one minute.

PMID- 22378376
TI  - Chemoprevention with green propolis green propolis extracted in L-lysine versus
      carcinogenesis promotion with L-lysine in N-Butyl-N-[4-hydroxybutyl] nitrosamine
      (BBN) induced rat bladder cancer.
AB  - PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP)
      and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The
      animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I
      was treated with propolis 30 days prior received BBN, and then these animals were
      treated daily with propolis; Groups II and III was treated with subcutaneous and
      oral propolis (respectively) concurrently with BBN. The animals of Group IV were
      treated L-lysine; Group V received water subcutaneous; and Group VI received only
      to BBN. Among the animals not submitted to carcinogenesis induction, Group VII
      received propolis, Group VIII received L-lysine and Group IX received water.
      RESULTS: The carcinoma incidence in Group I was lower than that of control (Group
      VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All
      animals treated with L-lysine developed carcinomas, and they were also more
      invasive in Group IV than in controls. On the other hand, Group VIII showed no
      bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder
      carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes
      promotion of bladder carcinogenesis.

PMID- 22378377
TI  - Histological features of peritoneal lavage with ropivacaine in rats with fecal
      peritonitis.
AB  - PURPOSE: To evaluate the histological features in lungs, peritoneum and liver of
      rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2%
      ropivacaine. METHODS: Twenty Wistar rats were subjected to laparotomy 6 h after
      the fecal peritonitis induction with autogenous stool. Rats were randomly
      distributed into 4 groups: I - (n=5) Control, no treatment; II - (n=5) Drying of
      the abdominal cavity; III - (n=5) Abdominal cavity lavage with 3 ml 0.9% saline
      solution and drying; and IV - (n=5) Abdominal cavity lavage with 3 ml 0.2%
      ropivacaine and drying. The animals that died underwent necropsy, and the
      surviving ones were subjected to euthanasia on the 11th day post-surgery.
      Fragments of liver, lungs and peritoneum were removed for histological
      evaluation. RESULTS: The animals that received peritoneal lavage (groups III and
      IV) showed greater survival than the drying and control groups. Lavage with
      ropivacaine prevented death during the observed period. Peritoneal lavage with
      ropivacaine maintained the architecture of the lung, peritoneum and liver without
      any important histological alterations. The histopathological findings analyzed
      correlated with greater survival of group IV. CONCLUSION: Treatment of fecal
      peritonitis in rats with peritoneal lavage using 0.2% ropivacaine demonstrated a
      reduction in histopathological alterations related to inflammatory response and
      sepsis.

PMID- 22378378
TI  - Stapedotomy: functional results with different diameter prostheses.
AB  - Developments in surgical technique and, more importantly, the use of increasingly
      sophisticated biocompatible prostheses have meant that good results can be
      achieved for otosclerosis sufferers in terms of restored hearing and very little
      postsurgical discomfort. We set out to assess whether the diameter of the
      prostheses used for stapedotomy (platinum piston/polytetrafluoroethylene, i.e.
      Teflon) has any effect on surgical outcome. Two groups of otosclerotic patients
      were selected, and these underwent stapedotomy surgery during the second phase of
      the disease. A piston-Teflon type prosthesis was used, 5.50 mm in terms of length
      but of different diameters (group A: 0.4 mm; group B: 0.6 mm). All the patients
      underwent the same pure-tone audiometry test before surgery, and then at 1 week
      and 1 month after surgery, to assess function. We compared air conduction after
      surgery with bone conduction before surgery. The data collected was analysed
      using the chi(2) (p < 0.05) test. This analysis showed that the results obtained
      with a 0.4-mm prosthesis or a 0.6-mm prosthesis are almost identical. There was
      no statistically significant difference in terms of hearing results when
      comparing either average tonal threshold or when analysing audiometric data
      frequency by frequency. It can be concluded, therefore, that in stapedotomy
      surgery, functional recovery is not affected by the diameter of the prosthesis
      used. A smaller diameter prosthesis is, however, the one of choice when the
      facial nerve is prominent or the oval window particularly narrow.

PMID- 22378379
TI  - Sildenafil treatment prevents glomerular hypertension and hyperfiltration in rats
      with renal ablation.
AB  - BACKGROUND: Sildenafil treatment ameliorates progressive renal injury resulting
      from extensive renal ablation; however, modifications induced by sildenafil in
      the glomerular hemodynamic pathophysiology of the remnant kidney have not been
      investigated. AIM: To determine the effects of sildenafil in the glomerular
      microcirculation and their relation to histological damage in the renal ablation
      model. METHODS: Micropuncture studies were performed 60 days after 5/6
      nephrectomy in rats that received no treatment, sildenafil (5 mg/kg/day) and
      reserpine, hydralazine and hydrochlorothiazide to maintain the blood pressure
      within normal levels. Sham-operated rats untreated and treated with sildenafil
      served as controls. RESULTS: As expected, renal ablation induced systemic and
      glomerular hypertension, hyperfiltration, proteinuria, glomerulosclerosis and
      tubulointerstitial inflammatory damage in the remnant kidney. Sildenafil
      treatment prevented single-nephron hyperfiltration and hypertension, suppressed
      renal arteriolar remodeling, ameliorated systemic hypertension and proteinuria,
      increased urinary excretion of cGMP and NO(2)(-)/NO(3)(-), decreased oxidative
      stress and improved histological damage in the remnant kidney. Normalization
      blood pressure with reserpine, hydralazine and hydrochlorothiazide did not modify
      glomerular hemodynamics, proteinuria or histological changes induced by renal
      ablation. CONCLUSIONS: Beneficial effects of sildenafil in the remnant kidney are
      associated with a reduction in the arteriolar remodeling, renal inflammatory
      changes and prevention of changes in the glomerular microcirculation.

PMID- 22378380
TI  - Total synthesis of (+)-chloranthalactone F.
AB  - Sequential biomimetic elaborations, featured by CrO(3)-mediated oxidative
      lactonization, and DDQ-involved oxidative enol-lactonization, ensured the concise
      total synthesis of (+)-chloranthalactone F.

PMID- 22378381
TI  - Consequences of two naturally occurring missense mutations in the structure and
      function of Bruton agammaglobulinemia tyrosine kinase.
AB  - Bruton agammaglobulinemia tyrosine kinase (BTK) is a key protein in the B-cell
      receptor (BCR) signaling pathway and plays an essential role in the
      differentiation of B lymphocytes. X-linked agammaglobulinemia (XLA) is a primary
      humoral immunodeficiency caused by mutations in the gene encoding BTK.
      Previously, we identified two novel variations, L111P and E605G, in BTK; these
      are localized within the pleckstrin homology and Src homology 1 domains,
      respectively. In the present study, we evaluated the potential effects of these
      variations on the structural conformation and the function of BTK. Using in
      silico methods, we found that the L111P and E650G variations are not located
      directly in protein-protein interfaces but close to them. They distorted the
      native structural conformation of the BTK protein, affecting not only its
      geometry and stability but also its ability for protein recognition and in
      consequence its functionality. To confirm the results of the in silico assays, WT
      BTK, L111P, and E650G variants were expressed in the BTK-deficient DT40 cell
      line. The mutant proteins exhibited an absence of catalytic activity, aberrant
      redistribution after BCR-crosslinking, and deficient intracellular calcium
      mobilization. This work demonstrates that L111 and E605 residues are fundamental
      for the activation and function of BTK.

PMID- 22378383
TI  - Role of FGFs/FGFRs in skeletal development and bone regeneration.
AB  - Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway
      involved in skeletal development. Missense mutations in FGFs and FGFRs were found
      clinically to cause multiple congenital skeleton diseases including
      chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate
      metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone
      regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs
      in the regulation of skeletal development, genetic skeletal diseases, and
      fracture healing will ultimately lead to better treatment of skeleton diseases
      caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major
      findings on the role of FGF signaling in skeletal development, genetic skeletal
      diseases and bone healing, and discusses issues that remain to be resolved in
      applying FGF signaling-related measures to promote bone healing. This review has
      also provided a perspective view on future work for exploring the roles and
      action mechanisms of FGF signaling in skeletal development, genetic skeletal
      diseases, and fracture healing.

PMID- 22378382
TI  - Arabidopsis trithorax-related3/SET domain GROUP2 is required for the winter
      annual habit of Arabidopsis thaliana.
AB  - The winter-annual habit of Arabidopsis thaliana requires active alleles of
      flowering locus C (FLC), which encodes a potent flowering repressor, and FRIGIDA
      (FRI), an activator of FLC. FLC activation by FRI is accompanied by an increase
      in specific histone modifications, such as tri-methylation of histone H3 at
      lysine 4 (H3K4me3), and requires three H3K4 methyltransferases, the Drosophila
      Trithorax-class Arabidopsis trithorax1 (ATX1) and ATX2, and yeast Set1-class ATX
      related7/set domain group25 (ATXR7/SDG25). However, lesions in all of these genes
      failed to suppress the enhanced FLC expression caused by FRI completely,
      suggesting that another H3K4 methyltransferase may participate in the FLC
      activation. Here, we show that ATXR3/SDG2, which is a member of a novel class of
      H3K4 methyltransferases, also contributes to FLC activation. An ATXR3 lesion
      suppressed the enhanced FLC expression and delayed flowering caused by an active
      allele of FRI in non-vernalized plants. The decrease in FLC expression in atxr3
      mutants was accompanied by reduced H3K4me3 levels at FLC chromatin. We also found
      that the rapid flowering of atxr3 was epistatic to that of atxr7, suggesting that
      ATXR3 functions in FLC activation in sequence with ATXR7. Our results indicate
      that the novel-class H3K4 methyltransferase, ATXR3, is a transcriptional
      activator that plays a role in the FLC activation and establishing the winter
      annual habit. In addition, ATXR3 also contributes to the activation of other FLC
      clade members, such as flowering locus M/MADS affecting flowering1 (FLM/MAF1) and
      MAF5, at least partially explaining the ATXR3 function in delayed flowering
      caused by non-inductive photoperiods.

PMID- 22378384
TI  - Evaluation of rural wastewater treatment processes in a county of eastern China.
AB  - With the rapid urbanization and industrialization in China, wastewater treatment
      in rural areas has become an increasing national concern. The selection of
      appropriate treatment processes closely based on the actual local status is
      crucial for the prevention of water quality deterioration in rural areas of
      China. This study presents a full year survey on the performances of various
      rural wastewater treatment processes at a county level in eastern China including
      seven three-chamber septic tanks (ST), five micro-power biological facilities
      (MP), seven constructed wetlands (CW), three stabilization ponds (SP) and five
      centralized activated sludge treatment plants (AS). It was found that although ST
      could remove a notable portion of total suspended solids (TSS) and chemical
      oxygen demand (COD(Cr)), it was ineffective in reducing nutrients and pathogens.
      Reliability and stability analyses showed that the centralized AS and
      decentralized CW processes outperformed the SP and MP processes. There were
      obvious discrepancies between the mean design concentrations, which ensure that
      95% of the effluents meet the discharge standards, and the actual effluent
      concentrations determined for each process. The expected compliance with the
      tentatively adopted second-grade discharge standards (GB 18918-2002) was
      unsatisfactory for most of the water quality parameters examined, indicating an
      urgent need to design more practical discharge standards for decentralized
      treatment processes. Based on an overall assessment of reliability, stability and
      cost-effectiveness, the centralized AS was suitable for densely populated towns
      while the decentralized CW was suitable for sparsely populated villages.

PMID- 22378385
TI  - Surface plasmon-waveguide hybrid polymer light-emitting devices using hexagonal
      Ag dots.
AB  - We investigated surface plasmon-waveguide hybrid resonances for enhancement of
      light emission in polymer light-emitting diodes (PLEDs). Hybrid waveguide-plasmon
      resonances in the visible range for waveguide mode and near IR range for surface
      plasmons were observed by incorporation of hexagonal Ag dot arrays. Considerable
      overlap between the emission wavelength of the PLEDs and the waveguide mode by an
      Ag dot array with a lattice constant of 500 nm was observed. Because of enhanced
      light extraction by Bragg scattering of waveguide modes, photoluminescence (PL)
      and electroluminescence (EL) were increased by 70% and 50%, respectively.

PMID- 22378386
TI  - Large area single-mode parity-time-symmetric laser amplifiers.
AB  - By exploiting recent developments associated with parity-time (PT) symmetry in
      optics, we here propose a new avenue in realizing single-mode large area laser
      amplifiers. This can be accomplished by utilizing the abrupt symmetry breaking
      transition that allows the fundamental mode to experience gain while keeping all
      the higher order modes neutral. Such PT-symmetric structures can be realized by
      judiciously coupling two multimode waveguides, one exhibiting gain while the
      other exhibits an equal amount of loss. Pertinent examples are provided for both
      semiconductor and fiber laser amplifiers.

PMID- 22378387
TI  - Observation of vector solitons with hidden vorticity.
AB  - This letter reports the first experimental observation, to our knowledge, of
      optical vector solitons composed of two incoherently coupled vortex components.
      We employ nematic liquid crystal to generate stable vector solitons with
      counterrotating vortices and hidden vorticity. In contrast, the solitons with
      explicit vorticity and corotating vortex components show azimuthal splitting.

PMID- 22378388
TI  - Extreme supercontinuum generation to the deep UV.
AB  - We report the formation of an ultrabroad supercontinuum down to 280 nm in the
      deep UV by pumping sharply tapered (5-30 mm taper lengths) solid-core photonic
      crystal fibers with 130 fs, 2 nJ pulses at 800 nm. The taper moves the point of
      soliton fission to a position where the core is narrower, a process that requires
      normal dispersion at the input face of the fiber. We find that the generation of
      deep-UV radiation is limited by strong two-photon absorption in the silica.

PMID- 22378389
TI  - 490 fs pulse generation from a passive C-band AlGaInAs/InP quantum well mode
      locked laser.
AB  - We report femtosecond pulses from a passive C-band two-section AlGaInAs/InP mode
      locked laser with a monolithically integrated passive waveguide made by quantum
      well intermixing. Without any external pulse compression, Lorentzian pulses are
      generated at a repetition frequency of ~38 GHz with 490 fs pulse duration, which
      is, to the best of our knowledge, the shortest pulse from any directly
      electrically pumped quantum well semiconductor mode-locked laser. The mode
      locking range is relatively large and the ultranarrow pulse width is very stable
      over a broad range of driving conditions.

PMID- 22378390
TI  - Light-into-heat conversion in La2O3:Er(3+)-Yb3+ phosphor: an incandescent
      emission.
AB  - Low-power-threshold cw laser-induced incandescence (CWLII) has been observed in
      La(2)O(3):Er(3+)-Yb(3+) phosphor on excitation by a 976 nm IR laser. It is
      suggested that incandescence originates from the extensive heating induced by the
      nonradiative processes taking place following the laser excitation. Other
      mechanisms for similar observations have also been suggested in the literature
      and have been discussed with the present observations. The estimated temperature
      for the CWLII approaches around 2650 K, and this seems to provide an effective
      way to rapidly attain high temperature in nano/microvolumes of phosphor. The
      phosphor exhibited efficient upconversion, and the ratio of the (2)H(11/2)
      >(4)I(15/2) and (4)S(3/2)->(4)I(15/2) band intensities of Er(3+) permits
      measurement of the temperature rise, from a distance.

PMID- 22378391
TI  - Large-aperture focusing of x rays with micropore optics using dry etching of
      silicon wafers.
AB  - Large-aperture focusing of Al K(alpha) 1.49 keV x-ray photons using micropore
      optics made from a dry-etched 4 in. (100 mm) silicon wafer is demonstrated.
      Sidewalls of the micropores are smoothed with high-temperature annealing to work
      as x-ray mirrors. The wafer is bent to a spherical shape to collect parallel x
      rays into a focus. Our result supports that this new type of optics allows for
      the manufacturing of ultralight-weight and high-performance x-ray imaging optics
      with large apertures at low cost.

PMID- 22378392
TI  - SOI-based trapezoidal waveguide with 45 degrees  microreflector for noncoplanar
      optical interconnect.
AB  - A silicon on insulator (SOI)-based trapezoidal waveguide with a 45 degrees 
      reflector for noncoplanar optical interconnect is demonstrated. The proposed
      waveguide is fabricated on an orientation-defined (100) SOI substrate by using a
      single-step anisotropic wet-etching process. The optical performances of proposed
      waveguides are numerically and experimentally studied. Transmittance of -4.51 dB,
      alignment tolerance of +/-20 MUm, cross talk of -53 dB, and propagation loss of 
      0.404 dB/cm are achieved The proposed waveguide would be a basic element and
      suitable for the future intrachip optical interconnects.

PMID- 22378393
TI  - Slow-light enhanced optical forces between longitudinally shifted photonic
      crystal nanowire waveguides.
AB  - We reveal that slow-light enhanced optical forces between side-coupled photonic
      crystal nanowire waveguides can be flexibly controlled by introducing a relative
      longitudinal shift. We predict that close to the photonic band edge, where the
      group velocity is reduced, the transverse force can be tuned from repulsive to
      attractive, and the force is suppressed for a particular shift value.
      Additionally the shift leads to symmetry breaking that can facilitate
      longitudinal forces acting on the waveguides, in contrast to unshifted structures
      where such forces vanish.

PMID- 22378394
TI  - Broadband terahertz pulse emission from ZnGeP2.
AB  - Optical rectification is demonstrated in (110)-cut ZnGeP(2) (ZGP) providing
      broadband terahertz (THz) generation. The source is compared to both GaP and GaAs
      over a wavelength range of 1150 nm to 1600 nm and peak-intensity range of 0.5
      GW/cm(2) to 40 GW/cm(2). ZGP peak-to-peak field amplitude is larger than in the
      other materials due to either lower nonlinear absorption or larger second-order
      nonlinearity. This material is well suited for broadband THz generation across a
      wide range of infrared excitation wavelengths.

PMID- 22378395
TI  - Heterodyne beatings between frequency-shifted feedback lasers.
AB  - Frequency-shifted feedback (FSF) lasers are potential candidates for long
      distance telemetry due to the appearance of beatings in the noise spectrum at the
      output of a homodyne interferometer: the frequencies of these beatings vary
      linearly with the path delay. In this Letter we demonstrate that these beatings
      also occur in the heterodyne mixing of two identical, but distinct, FSF lasers.
      This phenomenon is explained by the passive cavity model and is exploited to
      characterize the time-spectrum properties of FSF lasers. Consequences on
      telemetry with FSF lasers are presented.

PMID- 22378396
TI  - Nonlinear fiber-optic strain sensor based on four-wave mixing in microstructured
      optical fiber.
AB  - We demonstrate a nonlinear fiber-optic strain sensor, which uses the shifts of
      four-wave mixing Stokes and anti-Stokes peaks caused by the strain-induced
      changes in the structure and refractive index of a microstructured optical fiber.
      The sensor thus uses the inherent nonlinearity of the fiber and does not require
      any advanced postprocessing of the fiber. Strain sensitivity of -0.23
      pm/MUepsilon is achieved experimentally and numerical simulations reveal that for
      the present fiber the sensitivity can be increased to -4.46 pm/MUepsilon by
      optimizing the pump wavelength and power.

PMID- 22378397
TI  - Photonic ratchet superlattices by optical multiplexing.
AB  - We present a method based on incremental holographic multiplexing to create a
      refractive index ratchet distribution into a photorefractive crystal as an
      example for the generation principle of such complex multiperiodic lattices. The
      implemented technique follows a finite optical series expansion of the desired
      index modulation. To analyze the induced lattice, we determine the phase
      retardation of a probe beam at the back face of the crystal by digital holography
      analysis. Our result depicts a first example to optically explore the fascinating
      phenomena of ratchet resembling systems.

PMID- 22378398
TI  - Cross-phase modulation imaging.
AB  - We demonstrate a cross-phase modulation measurement technique based on the
      sensitive detection of modulation transfer in a pump-probe setup. By modulating
      the amplitude of the pump beam and spectrally analyzing the probe beam, we
      achieve a rapid, background-free measurement of nonlinear phase modulation using
      power levels acceptable in biological imaging. This measurement technique would
      allow the extension of widely employed phase microscopy methods to the nonlinear
      regime, providing intrinsic and universal nonlinear contrast for biological
      imaging.

PMID- 22378399
TI  - Microbolometer imaging spectrometer.
AB  - Newly developed, high-performance, long-wave- and mid-wave-IR Dyson spectrometers
      offer a compact, low-distortion, broadband, imaging spectrometer design. The
      design is further accentuated when coupled to microbolometer array technology.
      This novel coupling allows radiometric and spectral measurements of high
      temperature targets. It also serves to be unique since it allows for the system
      to be aligned warm. This eliminates the need for cryogenic temperature cycling.
      Proof of concept results are shown for a spectrometer with a 7.5 to 12.0 MUm
      spectral range and approximately 20 nm per spectral band (~200 bands). Results
      presented in this Letter show performance for remote hot targets (>200  degrees
      C) using an engineering grade spectrometer and IR commercial lens assembly.

PMID- 22378400
TI  - Postcompensation for nonlinearity of Mach-Zehnder modulator in radio-over-fiber
      system based on second-order optical sideband processing.
AB  - A postcompensation technique for nonlinearity of a Mach-Zehnder modulator in a
      radio-over-fiber (ROF) system is proposed and experimentally demonstrated based
      on second-order optical sideband processing and optical carrier band attenuation.
      The phase of the second-order optical sideband is shifted to suppress the third
      order intermodulation distortion (IMD3) in a direct detection ROF link. The
      optical carrier band is attenuated to make two kinds of origins of IMD3 have
      equal intensity and cancel each other out. A spurious-free dynamic range of 124.8
      dB.Hz(2/3) is achieved, which is about 25 dB more than that without compensation.

PMID- 22378401
TI  - Perfect imaging through a disordered waveguide lattice.
AB  - It is experimentally demonstrated that perfect imaging is possible in disordered
      wave guiding media, provided that the disorder is off-diagonal, i.e., that only
      the spacing varies randomly between the otherwise identical lattice sites. On
      diagonal disorder or Kerr nonlinearity destroys the imaging.

PMID- 22378402
TI  - Label-free 3D imaging of microstructure, blood, and lymphatic vessels within
      tissue beds in vivo.
AB  - This Letter reports the use of an ultrahigh resolution optical microangiography
      (OMAG) system for simultaneous 3D imaging of microstructure and lymphatic and
      blood vessels without the use of an exogenous contrast agent. An automatic
      algorithm is developed to segment the lymphatic vessels from the microstructural
      images based on the fact that the lymph fluid is optically transparent. An OMAG
      system is developed that utilizes a broadband supercontinuum light source,
      providing an axial resolution of 2.3 MUm and lateral resolution of 5.8 MUm,
      capable of resolving the capillary vasculature and lymphatic vessels innervating
      microcirculatory tissue beds. Experimental demonstration is performed by showing
      detailed 3D lymphatic and blood vessel maps, coupled with morphology, within
      mouse ears in vivo.

PMID- 22378403
TI  - Power characteristics of homogeneously broadened index-antiguided waveguide
      lasers.
AB  - A model is reported that describes a bidirectional homogeneously broadened index
      antiguided (IAG) slab laser having arbitrary single-pass gain and distributed
      losses. Maximum extraction efficiency and corresponding optimum output coupling
      are determined for various values of unsaturated gain and loss per pass. A method
      is proposed to determine the intrinsic laser parameters from output power
      measurements.

PMID- 22378404
TI  - Mid-IR soliton compression in silicon optical fibers and fiber tapers.
AB  - Numerical simulations are used to investigate soliton compression in silicon core
      optical fibers at 2.3 MUm in the mid-infrared waveguide regime. Compression in
      both standard silicon fibers and fiber tapers is compared to establish the
      relative compression ratios for a range of input pulse conditions. The results
      show that tapered fibers can be used to obtain higher levels of compression for
      moderate soliton orders and thus lower input powers.

PMID- 22378405
TI  - Manipulation of doughnut focal spot by image inverting interferometry.
AB  - Based on image inverting interference combined with phase modulation, we
      theoretically demonstrate that the doughnut focal spot can readily be
      manipulated, and either shrinkage or expansion of size of the central dark spot
      is possible in a large scale (peak-to-peak value: 0.555lambda-0.830lambda, or
      93.3%-140.8% compared with the standard one). As the interference and phase
      modulation can both be achieved by a double Porro prism, it is feasible to
      introduce this approach into optical tweezers to improve their performance. As
      much as 33.9% intensity of stimulated emission depletion (STED) beam can be
      reduced if the further optimized configuration is utilized in STED microscopy.

PMID- 22378406
TI  - Single-pixel polarimetric imaging.
AB  - We present an optical system that performs Stokes polarimetric imaging with a
      single-pixel detector. This fact is possible by applying the theory of
      compressive sampling to the data acquired by a commercial polarimeter without
      spatial resolution. The measurement process is governed by a spatial light
      modulator, which sequentially generates a set of preprogrammed light intensity
      patterns. Experimental results are presented and discussed for an object that
      provides an inhomogeneous polarization distribution.

PMID- 22378408
TI  - Generation of ultrasound in materials using continuous-wave lasers.
AB  - Generating and detecting ultrasound is a standard method of nondestructive
      evaluation of materials. Pulsed lasers are used to generate ultrasound remotely
      in situations that prohibit the use of contact transducers. The scanning rate is
      limited by the repetition rates of the pulsed lasers, ranging between 10 and 100
      Hz for lasers with sufficient pulse widths and energies. Alternately, a high
      power continuous-wave laser can be scanned across the surface, creating an
      ultrasonic wavefront. Since generation is continuous, the scanning rate can be as
      much as 4 orders of magnitude higher than with pulsed lasers. This paper
      introduces the concept, comparing the theoretical scanning speed with generation
      by pulsed laser.

PMID- 22378407
TI  - Addressable discrete-line-scanning multiphoton microscopy based on a spatial
      light modulator.
AB  - We developed a novel addressable discrete-line-scanning multiphoton microscope
      with high lateral and axial resolutions based on a spatial light modulator. Our
      discrete-line-focus design eliminates the cross talk that occurs in conventional
      one-dimensional line-scanning multiphoton microscopies. Additionally, a phase
      only spatial light modulator is able to scan only a sample's target area by
      generating a specific discrete line focus according to the shape and location of
      the target area. Compared with other multiphoton microscopies, this technique
      shortens scanning time and minimizes photodamage by concentrating scanning energy
      and dwell time on the area of interest.

PMID- 22378409
TI  - Photonic crystal cavity on optical fiber facet for refractive index sensing.
AB  - Using a micromanipulation technique, a planar photonic crystal nanocavity made
      from a thin semiconductor membrane is released from the host semiconductor and
      attached to the end facet of a standard single-mode optical fiber. The cavity
      spectrum can be read out through the fiber by detecting the photoluminescence of
      embedded quantum dots. The modified fiber end serves as a fiber-optic refractive
      index sensor.

PMID- 22378410
TI  - Agile linear interferometric method for carrier-envelope phase drift measurement.
AB  - A bandwidth-independent and linear interferometric method for the measurement of
      the carrier-envelope phase drift of ultrashort pulse trains is demonstrated. The
      pulses are temporally overlapped in a resonant multiple-beam interferometer. From
      the position of the spectral interference pattern, the relative carrier-envelope
      phase between two subsequent oscillator pulses is obtained at data acquisition
      rates up to 200 Hz. Cross calibration has been performed by f-to-2f
      interferometry in two independent experiments. The optical length of the
      interferometer has been actively stabilized, leading to a phase jitter of 117
      mrad (rms). These results indicate a reduced noise and quicker data acquisition
      in comparison with previous linear methods for measuring the carrier-envelope
      phase drift.

PMID- 22378411
TI  - Image-like illumination with LED arrays: design.
AB  - An array of spatially distributed light-emitting diodes (LEDs) can produce an
      illumination pattern that approaches an image by individually modulating each
      LED. In this letter, I analyze the first-order design of such systems in order to
      achieve the best match between the illumination distribution and a desired image.
      In particular, simple formulas are given for the optimal number of LEDs, working
      distance, array size, and LED beam pattern. The analysis developed here may be
      applied to the design of LED systems such as architecture lighting, energy
      efficient lighting, backlight local dimming for displays, and structured
      illumination microscopy with micro-LED arrays.

PMID- 22378412
TI  - Electro-optical detection based on large Kerr effect in polymer-stabilized liquid
      crystals.
AB  - In this Letter, polymer-stabilized liquid crystals with experimentally observed
      large electro-optic effect are introduced to the electro-optical detection to
      improve the voltage sensitivity. The Kerr constant of materials prepared in this
      study reached as high as 7.2*10(-9) m/V(2), increasing by 1000 times the
      sensitivity of the conventional electro-optical materials. The noncontact
      detection configuration, using a laser beam as a probe, enables quick two
      dimensional scanning measurements.

PMID- 22378413
TI  - Multitap microwave photonic filters with programmable phase response via optical
      frequency comb shaping.
AB  - We present a programmable multitap microwave photonic filter with an arbitrary
      phase response operating over a broad bandwidth. Complex coefficient taps are
      achieved by optical line-by-line pulse shaping on a 10 GHz flat optical frequency
      comb using a novel interferometric scheme. Through high-speed real-time
      measurements, we demonstrate programmable chirp control of a waveform via phase
      filtering. This achievement enables us to compress broadband microwave signals to
      their corresponding bandwidth-limited pulse duration.

PMID- 22378414
TI  - Rapid in-process measurement of surface roughness using adaptive optics.
AB  - We present an in-process measurement of surface roughness by combining an optical
      probe of laser-scattering phenomena and adaptive optics for aberration
      correction. Measurement results of five steel samples with a roughness ranging
      from 0.2 to 3.125 MUm demonstrate excellent correlation between the peak power
      and average roughness with a correlation coefficient (R(2)) of 0.9967. The
      proposed adaptive-optics-assisted system is in good agreement with the stylus
      method, and error values of less than 8.7% are obtained for average sample
      roughness in the range of 0.265 to 1.119 MUm. The proposed system can be used as
      a rapid in-process roughness monitor/estimator to further increase the precision
      and stability of manufacturing processes in situ.

PMID- 22378415
TI  - Crossed vortex bottle beam trap for single-atom qubits.
AB  - We demonstrate trapping and quantum state control of single cesium atoms in a 532
      nm wavelength bottle beam trap. The three-dimensional trap is formed by crossing
      two unit charge vortex beams. Single atoms are loaded with 50% probability
      directly from a magneto-optical trap. We achieve a trapping lifetime of up to 6 s
      and demonstrate fast Rabi oscillations with a coherence time of T(2)~43+/-9 ms.

PMID- 22378416
TI  - Adaptive coded-aperture imaging with subpixel superresolution.
AB  - We describe an adaptive coded-aperture imager operating in the midwave IR. This
      consists of a coded-aperture mask, a set of optics, and a 4k*4k focal plane array
      (FPA). This system can produce images with a resolution better than the detector
      pixel limit by combining multiple frames of data recorded with different coding.
      This superresolution capability has been demonstrated both in the laboratory and
      with targets placed outside, the highest resolution being one-half of the FPA
      pixel pitch.

PMID- 22378417
TI  - Multiple filamentation generated by focusing femtosecond laser with axicon.
AB  - Multiple filamentation has been observed when focusing a femtosecond laser pulse
      into a methanol solution with an axicon. It is found that multiple long filaments
      are located on the central spot and ring structures of the quasi-Bessel beam
      created by the axicon. Since the quasi-Bessel profile is determined by the axicon
      properties, the axicon has been suggested as a simple optics to control multiple
      filaments.

PMID- 22378418
TI  - Origin of thermally induced second harmonic generation in PbO-B2O3 glasses.
AB  - Optical second harmonic generation (SHG) with second-order nonlinearity chi((2))
      as high as 2.1 pm/V has been achieved in water quenched PbO-B(2)O(3) glasses. No
      nonlinear depletion layer or microcrystals were observed in these glasses and the
      mechanism for nonlinearity has been explored in this Letter. Our results show
      that the possible mechanism for SHG in these glasses can be attributed to their
      low thermal conductivity that led to a large surface stress gradient, which broke
      the inversion symmetry of the glasses and subsequently induced the nonlinear
      effect. These findings suggest that low thermal conductivity induced high stress
      gradients to lead to large SHG.

PMID- 22378419
TI  - Temperature sensor based on an isopropanol-sealed photonic crystal fiber in-line
      interferometer with enhanced refractive index sensitivity.
AB  - We fabricate a simple, compact, and stable temperature sensor based on a liquid
      sealed photonic crystal fiber (PCF) in-line nonpolarimetric modal interferometer.
      Different from other reported PCF devices, it does not need expensive
      polarimetric devices, and the liquid is sealed in one fiber. The device consists
      of a stub of isopropanol-filled PCF spliced between standard single-mode fibers.
      The temperature sensitivity (-166 pm/ degrees C) increases over an order of
      magnitude compared with those of the previous sensors based on air-sealed PCF
      interferometers built via fusion splicing with the same mechanism. In addition,
      the refractive index sensitivity also increases. Higher temperature sensitivity
      can be realized by infiltrating some liquid having a higher thermo-optic
      coefficient into the microholes of the PCF.

PMID- 22378420
TI  - Polarization-modulated analog photonic link with compensation of the dispersion
      induced power fading.
AB  - A novel integrable modulator consisting of a polarization modulator and a
      polarizer is proposed for constructing a high-performance analog photonic link.
      By adjusting a polarization controller placed before the modulator, both
      amplitude modulation and phase modulation with adjustable ratio between them are
      implemented. This feature is used to shift the peak of the frequency response of
      a dispersive link to any desired frequency, so the dispersion-induced power
      fading around the frequency is compensated. A proof-of-concept experiment is
      performed. The compensation of the dispersion-induced power fading in the
      proposed analog photonic link increases the spur-free dynamic range as large as
      12.5 dB.

PMID- 22378421
TI  - Characterization of dielectric spheres by spiral imaging.
AB  - We study the spiral spectra scattered off transparent dielectric spheres when
      probed by different Laguerre-Gaussian light beams, carrying nested topological
      wavefront dislocations. We show that such scattering data may be employed to
      determine geometrical properties of the spheres, such as their position. The
      technique is a generalization of standard Mie scattering, and it can be extended
      to study and to characterize nanospheres.

PMID- 22378422
TI  - Dual-modality photothermal optical coherence tomography and magnetic-resonance
      imaging of carbon nanotubes.
AB  - We demonstrate polyethylene-glycol-coated single-walled carbon nanotubes (CNTs)
      as contrast agents for both photothermal optical coherence tomography (OCT) and
      magnetic-resonance imaging (MRI). Photothermal OCT was accomplished with a
      spectral domain OCT system with an amplitude-modulated 750 nm pump beam using 10
      mW of power, and T(2) MRI was achieved with a 4.7 T animal system. Photothermal
      OCT and T(2) MRI achieved sensitivities of nanomolar concentrations to CNTs
      dispersed in amine-terminated polyethylene glycol, thus establishing the
      potential for dual-modality molecular imaging with CNTs.

PMID- 22378423
TI  - Chip-based frequency combs with sub-100 GHz repetition rates.
AB  - By fabricating high-Q silicon-nitride spiral resonators, we demonstrate frequency
      combs spanning over 200 nm with free spectral ranges (FSRs) of 80, 40, and 20 GHz
      using cascaded four-wave mixing. We characterize the RF beat note for the 20 GHz
      FSR comb, and the measured linewidth of 3.6 MHz is consistent with thermal
      fluctuations in the resonator due to amplitude noise of the pump source. These
      combs represent an important advance towards developing a complementary metal
      oxide-semiconductor (CMOS)-based system capable of linking the optical and
      electronic regimes.

PMID- 22378424
TI  - Dispersion-based control of modal characteristics for parametric down-conversion
      in a multimode waveguide.
AB  - We report generation of near-infrared photon pairs in fundamental spatial modes
      via type-II spontaneous parametric down-conversion in a periodically poled
      potassium titanyl phosphate (KTiOPO(4)) nonlinear waveguide supporting multiple
      transverse modes. This demonstrates experimentally a versatile scheme for
      controlling the spatial characteristics of the produced nonclassical light based
      on exploitation of intermodal dispersion. The down-converted photons are
      characterized by the measurement of the beam quality factors in the heralded
      regime.

PMID- 22378425
TI  - Use of a lensed fiber for a large-field-of-view, high-resolution, fiber-scanning
      microendoscope.
AB  - We report the application of a lensed fiber to a miniaturized fiber raster
      scanner in order to reduce the fiber's output beam size, thereby allowing for a
      compact and flexible endoscope capable of a large field of view (FOV) and high
      spatial resolution. For a proof of principle, the fabricated lensed fiber scanner
      is paired with a miniaturized gradient-index assembly to achieve a one-photon
      lateral resolution of 1.1 MUm with a FOV that has a diameter of 440 MUm.

PMID- 22378426
TI  - Generation of hard x rays by femtosecond laser pulse interaction with solid
      targets in atmosphere.
AB  - X ray radiation as high as 50 keV, including K(alpha) of Ba and Mo, have been
      observed from a solid target during the interaction of low energy ~0.65 mJ, 1 kHz
      40 femtosecond laser pulses focused in air at atmospheric pressure. Energetic
      electrons generating such x rays are possibly produced when the field strength in
      laser pulse wake exceeds the runaway threshold in air. Two dimensional particle
      in-cell simulations that include optical field ionization of air and elastic
      collisions support this mechanism.

PMID- 22378427
TI  - Thulium channel waveguide laser in a monoclinic double tungstate with 70% slope
      efficiency.
AB  - Laser experiments were performed on buried, ridge-type channel waveguides in an 8
      at. % thulium-doped, yttrium-gadolinium-lutetium codoped monoclinic double
      tungstate. A maximum slope efficiency of 70% and output powers up to 300 mW about
      2.0 MUm were obtained in a mirrorless laser resonator, by pumping with a
      Ti:sapphire laser near 800 nm. To the best of our knowledge, this result
      represents the most efficient 2 MUm channel waveguide laser to date. Lasing is
      obtained at various wavelengths between 1810 nm and 2037 nm.

PMID- 22378428
TI  - Spatial optical filter sensor based on hollow-core silica tube.
AB  - A spatial optical filter based on a hollow-core silica tube is proposed. Because
      of the hollow-core dimensions, it is possible to obtain a periodical spatial
      filter ranging from 1200 to 1700 nm with a channel spacing of 2.64 THz. The
      bandwidth is approximately 5.32 nm, and the isolation loss is ~30 dB. The optical
      losses are approximately ~0.67 dB/mm for a wavelength of 1500 nm. The 40 mm long
      spatial optical filter is tested as a sensing element and subjected to different
      physical parameters. The spatial optical filter is wavelength sensitive to strain
      and temperature, while for refractive-index variations there is an optical power
      dependency. This fiber structure can be used as a sensing element for extreme
      conditions, such as in very high temperature environments, where it presents a
      sensitivity of 27.5 pm  degrees C(-1).

PMID- 22378429
TI  - Dynamic Brillouin gratings permanently sustained by chaotic lasers.
AB  - A method to induce only one permanent and localized dynamic Brillouin grating in
      polarization maintaining optical fibers is introduced. The generation of the
      grating exploits the thumbtack correlation of the chaotic laser signals. A
      numerical calculation, corroborated by a theoretical analysis, is performed and
      the grating properties, length, and reflectance determined.

PMID- 22378430
TI  - Al(x)Ga(1-x)N-based deep-ultraviolet 320*256 focal plane array.
AB  - We report the synthesis, fabrication, and testing of a 320*256 focal plane array
      (FPA) of back-illuminated, solar-blind, p-i-n, Al(x)Ga(1-x)N-based detectors,
      fully realized within our research laboratory. We implemented a pulse atomic
      layer deposition technique for the metalorganic chemical vapor deposition growth
      of thick, high-quality, crack-free, high Al composition Al(x)Ga(1-x)N layers. The
      FPA is hybridized to a matching ISC 9809 readout integrated circuit and operated
      in a SE-IR camera system. Solar-blind operation is observed throughout the array
      with peak detection occurring at wavelengths of 256 nm and lower, and falling off
      three orders of magnitude by ~285 nm. By developing an opaque masking technology,
      the visible response of the ROIC is significantly reduced; thus the need for
      external filtering to achieve solar- and visible-blind operation is eliminated.
      This allows the FPA to achieve high external quantum efficiency (EQE); at 254 nm,
      average pixels showed unbiased peak responsivity of 75 mA/W, which corresponds to
      an EQE of ~37%. Finally, the uniformity of the FPA and imaging properties are
      investigated.

PMID- 22378431
TI  - Scaling submillimeter single-cycle transients toward megavolts per centimeter
      field strength via optical rectification in the organic crystal OH1.
AB  - We present the generation of high-power single-cycle terahertz (THz) pulses in
      the organic salt crystal 2-[3-(4-hydroxystyryl)-5.5-dimethylcyclohex-2
      enylidene]malononitrile or OH1. Broadband THz radiation with a central frequency
      of 1.5 THz (lambda(c)=200 MUm) and high electric field strength of 440 kV/cm is
      produced by optical rectification driven by the signal of a powerful femtosecond
      optical parametric amplifier. A 1.5% pump to THz energy conversion efficiency is
      reported, and pulse energy stability better than 1% RMS is achieved. An approach
      toward the realization of higher field strength is discussed.

PMID- 22378432
TI  - Observation of microsphere movement driven by optical pulse: comment.
AB  - We show that fiber-delivered, pulsed laser propulsion of glass microspheres, as
      observed in a recent Letter [Opt. Lett. 36, 1996 (2011).], due to only radiation
      pressure cannot explain the measured maximum velocity of microspheres. Our
      considerations, based on the reported results, indicate that the main momentum
      transfer mechanism is due to mass recoil that very likely follows a dielectric
      breakdown near or on the surface of the microsphere.

PMID- 22378433
TI  - Limitations of superoscillation filters in microscopy applications.
AB  - The idea of superresolving pupil filters comes from the concept of
      superoscillations that may occur in regions of a band-limited signal with small
      amplitude having oscillations faster than the fastest Fourier component of the
      signal. In optical microscopy, superresolution can be achieved by appropriate
      design of pupil functions where the angular aperture determines the ultimate
      focal spot smaller than the Abbe diffraction limit outside the evanescent field
      region. The angular aperture cannot be increased indefinitely and the huge
      sidelobes cannot be avoided that are present in superresolving filters. The
      limitations of using such kind of filters in microscopy applications are
      discussed through computational examples.

PMID- 22378434
TI  - Bilayer-fish-scale ultrabroad terahertz bandpass filter.
AB  - A bilayer fish-scale metamaterial is experimentally demonstrated to function as a
      broad bandpass filter in the terahertz regime. The measured 3 dB-bandwidth for
      normal incidence is 1.13 THz with a high transmittance. The measured transmission
      spectrum is described well by a model based on an RLC circuit and multiple
      reflections. The filter is relatively insensitive to incidence angles up to 45
      degrees .

PMID- 22378435
TI  - Nonparaxial TE and TM vector beams with well-defined orbital angular momentum.
AB  - A new formalism is developed for diffraction-free vector beams in free space. The
      solutions of Maxwell's equations are separated into two polarization modes, TE
      and TM. We discuss the validity of the method by applying it to a particular
      solution, the vectorial Bessel beam of order m.

PMID- 22378436
TI  - Limits for superfocusing with finite evanescent wave amplification.
AB  - Perfect lensing using negative refractive index materials and radiationless
      electromagnetic interference both provides extreme subwavelength focusing by
      "amplifying" evanescent wave components that are usually lost. This Letter
      provides a relation between the achievable focus spot size, the amplification
      available, and the focal length. This may be considered as a revised version of
      Abbe's diffraction limit for focusing systems that have evanescent wave
      amplification. It is useful in comparing the amplification achieved in various
      subwavelength focusing implementations as well as determining when it is better
      to use existing near-field techniques, such as simple diffraction from an
      aperture or slit, than to attempt complicated superfocusing.

PMID- 22378437
TI  - Amplification of the phase contrast signal at very high x-ray energies.
AB  - X-ray phase contrast imaging is increasingly being used in several fields, both
      at synchrotron facilities and with laboratory sources, due to its increased
      sensitivity compared to conventional x-ray methods. One important problem is the
      development of methods to make it suitable for use at very high x-ray energies,
      needed in many applications. We show how the edge illumination concept, which
      stands at the basis of the coded-aperture method, allows achieving hyperintense
      phase signals at energies close to 100 keV, by showing images of both weak phase
      objects and highly absorbing fossils with a high iron content.

PMID- 22378438
TI  - 5 MUm laser source for frequency metrology based on difference frequency
      generation.
AB  - A narrow-linewidth cw 5 MUm source based on difference frequency generation of a
      1.3 MUm quantum dot external cavity diode laser and a cw Nd:YAG laser in
      periodically poled MgO:LiNbO(3) has been developed and evaluated for
      spectroscopic applications. The source can be tuned to any frequency in the 5.09
      5.13 MUm range with an output power up to 0.1 mW, and in the 5.42-5.48 MUm range
      with sub-microwatt output. The output frequency is stabilized and its value
      determined by measuring the frequency of the two lasers with a remotely located
      frequency comb. A frequency instability of less than 4 kHz for long integration
      times and a linewidth smaller than 700 kHz were obtained.

PMID- 22378439
TI  - Realizable differential matrices for depolarizing media.
AB  - The evolution of a Stokes vector through depolarizing media is considered. A
      general form for the differential matrix is found that is appropriate in the
      presence of depolarization and it is parameterized in a manner that ensures that
      it yields, upon integration, a valid Mueller matrix for any choice of parameters.
      The form expands the more limited form for a nondepolarizing matrix given by
      Azzam [J. Opt. Soc. Am. 68, 1756 (1978)] and which was extended recently by
      others to include depolarization. A Mueller matrix decomposition is proposed that
      is based upon the new parameterization.

PMID- 22378440
TI  - Gouy phase for full-aperture spherical and cylindrical waves.
AB  - We investigate the Gouy phase shift for full-aperture waves converging to a focal
      point from all directions in two and three dimensions. We find a simple
      interpretation for the Gouy phase in this situation and show that it has a
      dramatic effect on reshaping sharply localized pulses.

PMID- 22378441
TI  - High-fidelity, 160 fs, 5 MUJ pulses from an integrated Yb-fiber laser system with
      a fiber stretcher matching a simple grating compressor.
AB  - Although femtosecond microjoule Yb-fiber systems are attractive because of a
      straightforward power scalability, they inherently suffer from a lowered pulse
      fidelity as a result of complex dispersion and nonlinearity management. Here, we
      present an integrated Yb-fiber system delivering high-fidelity microjoule pulses
      compressible down to 160 fs. The system uses a dispersion compensating fiber
      stretcher that is specially designed to match the dispersion of a 1480 lines/mm
      grating compressor. Performance analysis suggests the further possibility of
      scaling the pulse energy to tens of microjoules without pulse quality
      deterioration using this dispersion management scheme.

PMID- 22378442
TI  - Frequency domain aperture for the gain bandwidth reduction of stimulated
      Brillouin scattering.
AB  - In this Letter, we propose a novel method based on the inhomogeneous Brillouin
      gain saturation to reduce the gain bandwidth significantly below its natural
      value. Based on our first experiments, we report a decrease of the bandwidth in a
      standard single mode fiber down to 3 MHz.

PMID- 22378443
TI  - High-average-power, carrier-envelope phase-stable, few-cycle pulses at 2.1 MUm
      from a collinear BiB3O6 optical parametric amplifier.
AB  - We generate self-carrier-to-envelope phase-stable, 630 MUJ pulses, centered at
      2.1 MUm, with 42 fs (6 cycle) duration based on collinear optical parametric
      amplification in BiB(3)O(6) at 3 kHz. These pulses are generated through a
      traveling wave amplifier scheme, and the bandwidth supports 28 fs (4 cycle) pulse
      duration. Carrier-to-envelope phase stability was measured to be 410 mrad over 10
      min or 260 mrad over 35 s.

PMID- 22378444
TI  - Orthogonal-reference-pattern-modulated shift multiplexing for collinear
      holographic data storage.
AB  - A novel hybrid shift multiplexing method for collinear holographic data storage
      (CHDS) by using orthogonal reference patterns (RPs) is proposed, analyzed, and
      demonstrated. For this method, holograms are multiplexed by not only shifting the
      media but also using different RPs. Compared with the traditional method, the
      shift pitch for the hybrid method is substantially reduced because of the
      selectivity introduced by different RPs. The interpage cross talk due to Bragg
      mismatch and degeneracy for multiplexing holograms in the same volume by using
      orthogonal RPs is also attenuated by utilizing the shift selectivity of the
      hologram. A 1.5 MUm shift pitch is experimentally achieved by using three
      amplitude RPs in a system that would be 4.5 MUm with only one RP. This new method
      offers an alternative to significantly increase the data density and transfer
      rate of the CHDS system given that the media has ideal properties.

PMID- 22378445
TI  - Nanoparticle dispersion laser.
AB  - Lasing action from a dispersion of nanoparticles is reported for the first time
      to our knowledge. The nanoparticles are Nd(2)O(3) modified with
      dimethyldichlorosilane (DMDCS) in dimethylsulfoxide. The laser was pumped with a
      pulsed laser at 802 nm and yielded 2.7 mJ with a slope efficiency of 50%. This
      was compared to a standard Nd-doped phosphate glass that yielded very similar
      results in the same setup.

PMID- 22378446
TI  - All-optical switching based on inverse Raman scattering in liquid-core optical
      fibers.
AB  - We report on a new platform for all-optical switching based on inverse Raman
      scattering in liquids. Narrowband switching, which could be suitable for
      wavelength-division-multiplexed applications, is demonstrated using integrated
      liquid-core optical fiber infiltrated with both neat liquids (CCl(4) and CS(2))
      as well as an organic chromophore (beta-carotene) dissolved in CCl(4). Compared
      to standard glass optical fibers, these liquids have much larger Raman loss
      coefficients, which help reduce the pump power by at least an order of magnitude.
      Further improvements can be expected with the development of highly soluble
      organic compounds possessing large Raman cross sections.

PMID- 22378447
TI  - Widely linear and non-phase-matched optical-to-terahertz conversion on GaSe:Te
      crystals.
AB  - We demonstrate the widely linear and broadband terahertz (THz) generation on
      GaSe:Te crystals by femtosecond laser pulses. It was found that the dopant, Te
      atoms, in GaSe crystals significantly enhances the efficiency of THz generation,
      and its central frequency can be tuned by varying the crystal thickness through
      non-phase-matched optical rectification. Moreover, the wide-ranging linearity for
      the optical-to-THz conversion and central-frequency-tunable THz generation
      promise for GaSe:Te crystals to be potential materials for high-power (>1.36 MUW)
      THz applications.

PMID- 22378448
TI  - Extraction of intrinsic fluorescence from single fiber fluorescence measurements
      on a turbid medium.
AB  - This study utilizes Monte Carlo simulations of single fiber fluorescence to
      develop an empirical model that corrects for the influence of scattering and
      absorption on fluorescence intensity (F(SF)). The model expresses F(SF) in terms
      of the reduced scattering coefficient (MUs') and absorption coefficient (MU(a)),
      each determined independently at excitation and emission wavelengths (lambda(x)
      and lambda(m)), and the fiber diameter (d(f)). This model returns accurate
      descriptions (mean residual <6%) of F(SF) across a biologically relevant range of
      MUs' and MU(a) values and is insensitive to the form of the scattering phase
      function.

PMID- 22378449
TI  - Source location from fluorescence lifetime in disordered media.
AB  - We show that the source location problem can be solved in a scattering medium
      using the fluorescence lifetime and realistic a priori information. The intrinsic
      ill-posedness of the problem is reduced when the level of scattering increases.
      This work is a proof of principle demonstrating the high potential of
      quantitative lifetime imaging in complex media.

PMID- 22378450
TI  - Efficient femtosecond pulse generation in an all-normal-dispersion Yb:fiber ring
      laser at 605 MHz repetition rate.
AB  - We report a 1030 nm-wavelength Yb:fiber laser that produces the shortest/direct
      output pulse duration (502 fs) among all-normal-dispersion fiber lasers at the
      highest repetition rate (605 MHz) among the passively fundamentally mode-locked
      fiber lasers. The laser also exhibits an optical efficiency of 70% at CW and 65%
      at mode-locking modes.

PMID- 22378451
TI  - Multibeam second-harmonic generation by spatiotemporal shaping of femtosecond
      pulses.
AB  - We present a technique for efficient generation of the second-harmonic signal at
      several points of a nonlinear crystal simultaneously. Multispot operation is
      performed by using a diffractive optical element that splits the near-infrared
      light of a mode-locked Ti:sapphire laser into an arbitrary array of beams that
      are transformed into an array of foci at the nonlinear crystal. We show that, for
      pulse temporal durations under 100 fs, spatiotemporal shaping of the pulse is
      mandatory to overcome chromatic dispersion effects that spread both in space and
      time the foci showing a reduced peak intensity that prevents nonlinear phenomena.
      We experimentally demonstrate arbitrary irradiance patterns for the second
      harmonic signal consisting of more than 100 spots with a multipass amplifier
      delivering 28 fs, 0.8 mJ pulses at 1 kHz repetition rate.

PMID- 22378452
TI  - Terahertz photonic states in semiconductor-graphene cylinder structures.
AB  - We propose a semiconductor-graphene cylinder that can serve as a terahertz (THz)
      photonic crystal. In such a structure, graphene plays a role in achieving a
      strong mismatch of the dielectric constant at the semiconductor-graphene
      interface due to its two-dimensional nature and relatively low value of the
      dielectric constant. We find that when the radius of the outer semiconductor
      layer is about rho(1)~100 MUm, the frequencies of the photonic modes are within
      the THz bandwidth and they can be efficiently tuned via varying rho(1).
      Furthermore, the dispersion relation of the photonic modes shows that a
      semiconductor-graphene cylinder is of excellent light transport properties, which
      can be utilized for the THz waveguide. This study is pertinent to the application
      of graphene as THz photonic devices.

PMID- 22378453
TI  - Statistical similarity and cross-spectral purity of stationary stochastic fields.
AB  - In practical situations, one often generates a beam by superposition of two or
      more light beams. The beam generated by superposition displays, in general,
      different spectral properties than do the original beams. However, there are some
      optical beams, called cross-spectrally pure beams, which can generate a light
      beam of identical spectral distribution on superposition. The relationship
      between cross-spectral purity and spatial coherence has been the subject of
      investigations for some time. Recently, a concept of so-called statistical
      similarity has been introduced which provides a new way to elucidate complete
      spatial coherence. In this Letter, we discuss some implications of statistical
      similarity of an optical field on its cross-spectral purity.

PMID- 22378454
TI  - Stokes holography.
AB  - A new technique, referred to as Stokes holography, is proposed and experimentally
      demonstrated for controlled synthesis of generalized Stokes parameters in 3D
      space using Stokes fringes. Stokes fringes are polarization fringes which permit
      to record and reconstruct complete wavefront. Full use of Stokes fringes in a
      single step is realized by scattering complex field and subsequently
      reconstructing using spatial averaging of the randomly scattered field.
      Mathematical formulations are derived and supported by experimental results of 3D
      object reconstruction in generalized Stokes parameters.

PMID- 22378455
TI  - Photonic-chip-based tunable slow and fast light via stimulated Brillouin
      scattering.
AB  - We report the first (to our knowledge) demonstration of photonic chip based
      tunable slow and fast light via stimulated Brillouin scattering. Slow, fast, and
      negative group velocities were observed in a 7 cm long chalcogenide (As(2)S(3))
      rib waveguide with a group index change ranging from ~-44 to +130, which results
      in a maximum delay of ~23 ns at a relatively low gain of ~23 dB. Demonstration of
      large tunable delays in a chip scale device opens up applications such as
      frequency sensing and true-time delay for a phased array antenna, where
      integration and delays ~10 ns are highly desirable.

PMID- 22378456
TI  - Vectorial laws of refraction and reflection using the cross product and dot
      product.
AB  - We demonstrate that published vectorial laws of reflection and refraction of
      light based solely on the cross product do not, in general, uniquely determine
      the direction of the reflected and refracted waves without additional
      information. This is because the cross product does not have a unique inverse
      operation, which is explained in this Letter in linear algebra terms. However, a
      vector is in fact uniquely determined if both the cross product (vector product)
      and dot product (scalar product) with a known vector are specified, which can be
      written as a single equation with a left-invertible matrix. It is thus possible
      to amend the vectorial laws of reflection and refraction to incorporate both the
      cross and dot products for a complete specification with unique solution. This
      enables highly efficient, unambiguous computation of reflected and refracted wave
      vectors from the incident wave and surface normal.

PMID- 22378457
TI  - Design of a subnanometer resolution beam position monitor for dielectric laser
      accelerators.
AB  - We present a new concept for a beam position monitor with the unique ability to
      map particle beam position to a measurable wavelength. Coupled with an optical
      spectrograph, this beam position monitor is capable of subnanometer resolution.
      We describe one possible design, and through finite-element frequency-domain
      simulations, we show a resolution of 0.7 nm. Because of its high precision and
      ultracompact form factor, this device is ideal for future x-ray sources and laser
      driven particle accelerators "on a chip."

PMID- 22378458
TI  - Fano resonance analysis in a pair of semiconductor quantum dots coupling to a
      metal nanowire.
AB  - We investigate theoretically a surface plasmon transport in the metal nanowire
      coupling to a pair of quantum dots. The Fano-type transmission spectrum is
      analyzed. The phase shift and group velocity delay of the transmitted surface
      plasmon are explored. The electromagnetically-induced-transparency-type
      transmission spectrum is also discussed.

PMID- 22378459
TI  - Optical detection of indocyanine green encapsulated biocompatible poly (lactic-co
      glycolic) acid nanoparticles with photothermal optical coherence tomography.
AB  - We describe a functional imaging paradigm that uses photothermal optical
      coherence tomography (PT-OCT) to detect indocyanine green (ICG)-encapsulated
      biocompatible poly(lactic-co-glycolic) acid (PLGA) nanoparticles embedded in
      highly scattering tissue phantoms with high resolution and sensitivity. The ICG
      loaded PLGA nanoparticles were fabricated using a modified emulsification solvent
      diffusion method. With a 20 kHz axial scan rate, PT-OCT based on spectral-domain
      interferometric configuration at 1310 nm was used to detect phase changes induced
      by a 808 nm photothermal excitation of ICG-encapsulated PLGA nanoparticles. An
      algorithm based on Fourier transform analysis of differential phase of the
      spectral interferogram was developed for detecting the depth resolved localized
      photothermal signal. Excellent contrast difference was observed with PT-OCT
      between phantoms containing different concentrations of ICG-encapsulated PLGA
      nanoparticles. This technique has the potential to provide simultaneous
      structural and molecular-targeted imaging with excellent signal-to-noise for
      various clinical applications.

PMID- 22378460
TI  - Spin polarization separation of light reflected  at Brewster angle.
AB  - A spin polarization separation of reflected light is observed, when a linearly
      polarized Gaussian beam impinges on an air-glass interface at Brewster angle. In
      the far-field zone, spins of photons are oppositely polarized in two regions
      along the direction perpendicular to incident plane. Spatial scale of this
      polarization is related to optical properties of dielectric and can be controlled
      by experimental configuration. We believe that this study benefits the
      manipulation of spins of photons and the development of methods for investigating
      optical properties of materials.

PMID- 22378461
TI  - Plasma-assisted coherent backscattering for standoff spectroscopy.
AB  - We show that an intense coherent backward signal can be generated through a Raman
      type four-wave-mixing process using forward propagating fields only. Phase
      matching for this process is achieved through a plasma modulation of the
      refractive index. Applications to standoff spectroscopy are discussed.

PMID- 22378462
TI  - Analysis of a mathematical model for the growth of cancer cells.
AB  - In this paper, a 2D model for the growth of multilayer tumours is presented. The
      model consists of a free boundary problem for the tumour cell membrane and the
      tumour is supposed to grow or shrink due to cell proliferation or cell dead. The
      growth process is caused by a diffusing nutrient concentration sigma and is
      controlled by an internal cell pressure p. We assume that the tumour occupies a
      strip-like domain with a fixed boundary at y = 0 and a free boundary y = rho(x),
      where rho is a 2pi-periodic function. First, we prove the existence of solutions
      (sigma, p, rho) on a scale of small Hoolder spaces and show that our model allows
      for flat stationary solutions. As a main result, we establish that these
      equilibrium points are locally asymptotically stable under small perturbations.

PMID- 22378463
TI  - An asymptotic model of particle deposition at an airway bifurcation.
AB  - Particle transport and deposition associated with flow over a wedge is
      investigated as a model for particle transport and flow at the carina of an
      airway bifurcation during inspiration. Using matched asymptotics, a uniformly
      valid solution is obtained to represent the high Reynolds number flow over a
      wedge that considers the viscous boundary layer near the wedge and the outer
      inviscid region and is then used to solve the particle transport equations.
      Sometimes particle impaction on the wedge is prevented due to the boundary layer.
      We call this boundary layer shielding (BLS). This effect can be broken down into
      different types: rejection, trapping and deflection that are described by what
      happens to the particle's initial negative velocity normal to the wall either
      changing sign, reaching zero, or remaining negative in the boundary layer region.
      The deposition efficiency depends on the critical Stokes number but exhibits a
      weak dependence on Reynolds number. Deposition efficiency for S(c) in the range 0
      < S(c) < 0.4 yields the following relationship De ~ (1.867S(c)1.78-0.016)
      sin(betapi/2) at large Reynolds numbers, where betapi is the wedge angle. For a
      specific deposition efficiency, S(c) decreases as betapi increases. The
      distribution of impacted particles was also computed and revealed that particles
      primarily impact within one airway diameter of the carina, consistent with
      computational fluid dynamics approaches. This work provides a new insight that
      the BLS inherent to the wedge component of the structure is the dominant reason
      for the particle distribution. This finding is important in linking aerosol
      deposition to the location of airway disease as well as target sites for
      therapeutic deposition.

PMID- 22378464
TI  - Novel molecular targets regulated by tumor suppressors microRNA-1 and microRNA
      133a in bladder cancer.
AB  - Our expression signatures of human cancer including bladder cancer (BC) revealed
      that the expression of microRNA-1 (miR-1) and microRNA-133a (miR-133a) is
      significantly reduced in cancer cells. In the human genome, miR-1 and miR-133a
      are located on the same chromosomal region (miR-1-2 and miR-133a-1 on 18q11.2,
      and miR-1-1 and miR-133a-2 on 20q13.33) called cluster. In this study, we
      identified the novel molecular targets commonly regulated by miR-1 and miR-133a
      in BC. Genome-wide molecular target search and luciferase reporter assays showed
      that prothymosin-alpha (PTMA) and purine nucleoside phosphorylase (PNP) are
      directly regulated by miR-1 and miR-133a. Silencing of these two genes
      significantly inhibited cell proliferation and invasion, and increased apoptosis
      in BC cells. Immunohistochemistry showed that PTMA expression levels were
      significantly higher in BC compared to normal bladder epitheliums. PTMA and PNP
      were identified as new target genes regulated by the miR-1 and miR-133a cluster
      in BC. These genes may function as oncogenes contributing to cell proliferation
      and invasion in BC. Tumor suppressive miR-1 and miR-133a-mediated novel molecular
      targets may provide new insights into the potential mechanisms of BC oncogenesis.

PMID- 22378465
TI  - Regulation of pi-stacked anthracene arrangement for fluorescence modulation of
      organic solid from monomer to excited oligomer emission.
AB  - The construction and precise control of the face-to-face pi-stacked arrangements
      of anthracene fluorophores in the crystalline state led to a remarkable red shift
      in the fluorescence spectrum due to unprecedented excited oligomer formation. The
      arrangements were regulated by using organic salts including anthracene-1,5
      disulfonic acid (1,5-ADS) and a variety of aliphatic amines. Because of the
      smaller number of hydrogen atoms at the edge positions and the steric effect of
      the sulfonate groups, 1,5-ADS should prefer face-to-face pi-stacked arrangements
      over the usual edge-to-face herringbone arrangement. Indeed, as the alkyl
      substituents were lengthened, the organic salts altered their anthracene
      arrangement to give two-dimensional (2D) edge-to-face and end-to-face herringbone
      arrangements, one-dimensional (1D) face-to-face zigzag and slipped stacking
      arrangements, a lateral 1D face-to-face arrangement like part of a brick wall,
      and a discrete monomer arrangement. The monomer arrangement behaved as a dilute
      solution even in the close-packed solid state to emit deep blue light. The 1D
      face-to-face zigzag and slipped stacking of the anthracene fluorophores caused a
      red shift of 30-40 nm in the fluorescence emission with respect to the discrete
      arrangement, probably owing to ground-state associations. On the other hand, the
      2D end-to-face stacking induced a larger red shift of 60 nm, which is attributed
      to the excimer fluorescence. Surprisingly, the brick-like lateral face-to-face
      arrangement afforded a remarkable red shift of 150 nm to give yellow
      fluorescence. This anomalous red shift is probably due to excited oligomer
      formation in such a lateral 1D arrangement according to the long fluorescence
      lifetime and little shift in the excitation spectrum. The regulation of the pi
      stacked arrangement of anthracene fluorophores enabled the wide modulation of the
      fluorescence and a detailed investigation of the relationships between the
      photophysical properties and the arrangements.

PMID- 22378466
TI  - Post-percutaneous nephrolithotomy septic shock and severe hemorrhage: a study of
      risk factors.
AB  - OBJECTIVE: To identify the risk factors predicting septic shock and severe
      hemorrhage in percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively
      analyzed 420 renal calculi patients who underwent ultrasound-guided PCNL from
      March 2005 to May 2011. Data on patients who experienced infectious shock
      requiring anti-shock therapy and severe renal bleeding requiring angiographic
      renal embolization or nephrectomy were compared with other patients using
      univariate analyses. RESULTS: Of 420 patients, 10 (2.4%) suffered septic shock
      and 4 (1%) had severe hemorrhage. The two significant risk factors for infectious
      shock were preoperative urine white blood cell count and operation time. For
      severe bleeding the absence of hydronephrosis and puncture time were significant
      risk factors. Operation time >90 min was associated with both septic shock and
      severe renal bleeding (p = 0.017). In contrast, the risk of encountering severe
      renal bleeding was higher if a nephroscope rather than a ureteroscope was used (p
      = 0.045). CONCLUSIONS: Operation time was a risk factor for both septic shock and
      severe hemorrhage. The patients without hydronephrosis before operation were more
      likely to suffer severe renal bleeding. Reducing intraoperative puncture time can
      reduce the probability of severe post-PCNL hemorrhage. The use of a comparatively
      gross nephroscope passage was likely to result in severe renal bleeding.

PMID- 22378467
TI  - Aquaporin-4 and epilepsy.
AB  - Recent studies have implicated glial cells in modulation of synaptic
      transmission, so it is plausible that glial cells may have a functional role in
      the hyperexcitability characteristic of epilepsy. Indeed, alterations in distinct
      astrocyte membrane channels, receptors, and transporters have all been associated
      with the epileptic state. This review focuses on the potential roles of the glial
      water channel aquaporin-4 (AQP4) in modulation of brain excitability and in
      epilepsy. We will review studies of mice lacking AQP4 (Aqp4(-/-) mice) or alpha
      syntrophin (an AQP4 anchoring protein) and discuss the available human studies
      demonstrating alterations of AQP4 in human epilepsy tissue specimens. We will
      conclude with new studies of AQP4 regulation and discuss the potential role of
      AQP4 in the development of epilepsy (epileptogenesis). While many questions
      remain unanswered, the available data indicate that AQP4 and its molecular
      partners may represent important new therapeutic targets.

PMID- 22378468
TI  - PKMzeta is necessary and sufficient for synaptic clustering of PSD-95.
AB  - The persistent activity of protein kinase Mzeta (PKMzeta), a brain-specific,
      constitutively active protein kinase C isoform, maintains synaptic long-term
      potentiation (LTP). Structural remodeling of the postsynaptic density is believed
      to contribute to the expression of LTP. We therefore examined the role of PKMzeta
      in reconfiguring PSD-95, the major postsynaptic scaffolding protein at excitatory
      synapses. In primary cultures of hippocampal neurons, PKMzeta activity was
      critical for increasing the size of PSD-95 clusters during chemical LTP (cLTP).
      Increasing PKMzeta activity by overexpressing the kinase in hippocampal neurons
      was sufficient to increase PSD-95 cluster size, spine size, and postsynaptic
      AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMzeta did not
      increase PSD-95 clustering, and applications of the zeta-pseudosubstrate
      inhibitor ZIP reversed the PKMzeta-mediated increases in PSD-95 clustering,
      indicating that the activity of PKMzeta is necessary to induce and maintain the
      increased size of PSD-95 clusters. Thus the persistent activity of PKMzeta is
      both necessary and sufficient for maintaining increases of PSD-95 clusters,
      providing a unified mechanism for long-term functional and structural
      modifications of synapses.

PMID- 22378469
TI  - The optimal timing of antihypertensive medication administration for morning
      hypertension in patients with cerebral infarction.
AB  - Morning hypertension is an independent risk factor for cardiovascular diseases,
      particularly stroke. However, the optimal time at which to take antihypertensive
      medication to treat morning hypertension remains unclear. We prospectively
      enrolled elderly patients (over 65 years old) with morning hypertension who had
      suffered an ischemic stroke (or strokes). Additional treatments (one of six arms)
      were randomly administered for 10 weeks in the morning, in the evening or at
      bedtime (n=15 for each time point/medication). The patients measured their blood
      pressure and heart rate at home for 14 days prior to the intervention and for the
      final 14 days, and recorded the data in a blood pressure diary. The patients'
      urinary albumin/creatinine ratios were evaluated before and after the 10-week
      intervention. A total of 270 patients were enrolled in this study (mean age:
      75.6+/-5.8 years; female/male ratio: 125/145). Their morning and evening systolic
      blood pressures were significantly decreased after following any of the study
      medication dosing schedules (P<0.001). However, the reductions in the differences
      between the morning and evening systolic blood pressures were significant only
      when the medication was taken in the evening or at bedtime (P<0.001 with repeated
      measures analysis of variance). Furthermore, the recovery rate from morning
      hypertension was also higher when the medication was taken in the evening (40.0%)
      or at bedtime (45.6%), rather than in the morning (22.2%; P=0.003 with the chi(2)
      test). Antihypertensive medication taken in the evening or at bedtime is the most
      effective in treating morning hypertension when the patient adheres to the
      medication regimen.

PMID- 22378470
TI  - Nocturnal blood pressure and cardiovascular disease: a review of recent advances.
AB  - The accurate measurement, prediction and treatment of high blood pressure (BP)
      are essential issues in the management of hypertension. Ambulatory blood pressure
      monitoring (ABPM) has been shown to be superior to clinic BP measurements as ABPM
      can provide the following important information: (i) the mean BP levels, (ii) the
      diurnal variation in BP and (iii) the short-term BP variability. Among these
      parameters, there is increasing evidence that the mean nocturnal BP level is the
      most sensitive predictor of cardiovascular morbidity and mortality. Furthermore,
      several studies have shown that less nocturnal BP dipping, defined as less
      nocturnal BP decline relative to daytime BP, or a high night-day BP ratio was
      associated with poor prognosis irrespective of the 24-hour BP levels. These
      findings can be interpreted in at least two ways: namely, high nocturnal BP or
      less nocturnal BP dipping might be not only a potent risk factor for
      cardiovascular disease (CVD), but also a marker of pre-existing or concurrent
      diseases that can lead to nocturnal BP elevation. In this review, we consider the
      clinical utility of ABPM and in particular focus on the nocturnal BP levels or
      nocturnal BP dipping as a potent risk factor for CVD. In addition, the clinical
      management of high nocturnal BP and blunted nocturnal BP dipping with
      antihypertensive medications is discussed.

PMID- 22378471
TI  - Cure for a resistant hypertension case that required seven drugs for blood
      pressure control.

PMID- 22378472
TI  - Silent brain infarct is independently associated with arterial stiffness
      indicated by cardio-ankle vascular index (CAVI).
AB  - It is still unclear whether silent brain infarct (SBI) and white-matter
      hyperintensities (WMHs) on magnetic resonance imaging (MRI) scans are associated
      with cardio-ankle vascular index (CAVI), a novel parameter of arterial stiffness.
      We studied 220 consecutive patients (mean age, 69 years) without a history of
      stroke or transient ischemic attack. Patients were assessed for the presence of
      SBI, WMHs and risk factors. Arterial stiffness was evaluated using CAVI. Patients
      were categorized into one of two groups according to the presence or absence of
      SBI and WMHs, and clinical characteristics were compared between the two groups.
      CAVI was significantly higher in patients with SBI or in patients with WMHs than
      in those without those respective findings. The CAVI cutoff values for detection
      of SBI and WMHs were 9.2 and 8.9, respectively. On multivariable analyses, CAVI,
      a one point increase in CAVI: odds ratio (OR), 1.25; 95% confidence interval
      (CI), 1.01-1.56; CAVI >=9.2: OR, 2.34; 95% CI, 1.16-5.02, was independently
      associated with SBI, however, CAVI was not independently associated with WMHs.
      Patients with CAVI >=9.2 had higher OR for the presence of both SBI and WMHs (OR,
      2.57; 95% CI, 1.15-5.98) when compared with patients with CAVI <9.2 after
      adjustment for age and sex. SBI is independently associated with arterial
      stiffness indicated by CAVI.

PMID- 22378473
TI  - Augmentation index is related to white matter lesions.
AB  - The augmentation index (AIx) is a measure of pulse wave reflection from
      peripheral muscular conduit arteries, and is assumed to increase with stiffened
      arteries. A white matter lesion (WML) is generally regarded as a chronic ischemic
      lesion, which is associated with cerebral small-vessel arteriosclerosis. The aim
      of this study is to elucidate the effect of pulse wave reflection on the brain.
      Carotid AIx was measured in a total of 205 neurologically normal adults. The
      correlations between AIx and WML were investigated. Two categories of WML were
      evaluated, periventricular hyperintensity (PVH) and deep and subcortical white
      matter hyperintensity (DSWMH). On univariate analysis, AIx was significantly
      correlated with the grades of PVH and DSWMH (P=0.0001, respectively). On
      multivariate analysis, AIx was correlated with PVH and DSWMH, independent of
      other risk factors such as age or blood pressure. Pulse wave reflection from
      small vessels may influence the genesis of WML.

PMID- 22378474
TI  - Vibrational manifestations of strong non-Condon effects in the H3O(+).X3 (X = Ar,
      N2, CH4, H2O) complexes: a possible explanation for the intensity in the
      "association band" in the vibrational spectrum of water.
AB  - The harmonic approximation provides a powerful approach for interpreting
      vibrational spectra. In this treatment, the energy and intensity of the 3N- 6
      normal modes are calculated using a quadratic expansion of the potential energy
      and a linear expansion of the dipole moment surfaces, respectively. In reality,
      transitions are often observed that are not accounted for by this approach (e.g.
      combination bands, overtones, etc.), and these transitions arise from inherent
      anharmonicities present in the system. One interesting example occurs in the
      vibrational spectrum of H(2)O((l)), where a band is observed near 2000 cm(-1)
      that is commonly referred to as the "association band". This band lies far from
      the expected bend and stretching modes of the water molecule, and is not
      recovered at the harmonic level. In a recent study, we identified a band in this
      spectral region in gas-phase clusters involving atomic and molecular adducts to
      the H(3)O(+) ion. In the current study we probe the origins of this band through
      a systematic analysis of the argon-predissociation spectra of H(3)O(+).X(3) where
      X = Ar, CH(4), N(2) or H(2)O, with particular attention to the contributions from
      the non-linearities in the dipole surfaces, often referred to as non-Condon
      effects. The spectra of the H(3)O(+) clusters all display strong transitions
      between 1900-2100 cm(-1), and theoretical modeling indicates that they can be
      assigned to a combination band involving the HOH bend and frustrated rotation of
      H(3)O(+) in the solvent cage. This transition derives its oscillator strength
      entirely from strong non-Condon effects, and we discuss its possible relationship
      to the association band in the spectrum of liquid water.

PMID- 22378475
TI  - Age-graded reductions in quadriceps muscle strength and peak aerobic capacity in
      COPD.
AB  - BACKGROUND: Reductions in quadriceps strength and peak aerobic capacity (VO2) in
      patients with chronic obstructive pulmonary disease (COPD) have been studied in
      relatively small samples over a short period. Moreover, results were not
      corrected for confounding variables, such as lean muscle mass, gender, and gas
      transfer capacity of the lungs. OBJECTIVES: To compare quadriceps muscle strength
      and peak V.O2 in women and men while stratifying for age and gas transfer
      capacity. We then corrected for lower-limb lean muscle mass to see whether and to
      what extent the age-graded reduction remained evident. METHODS: Retrospectively,
      data of 374 women and 593 men with COPD were analyzed: lung function, current
      drug therapy, quadriceps strength, peak V.O2, lower-limb lean muscle mass, and
      gas transfer capacity. RESULTS: Quadriceps strength and peak V.O2 were lower in
      older women and men with a gas transfer capacity of <50% predicted, also after
      adjustment for lower-limb lean muscle mass. Moreover, quadriceps strength and
      peak V.O2 were lower in older women and men with a gas transfer capacity of <50%
      predicted, also after adjustment for lower-limb lean muscle mass. Moreover,
      quadriceps strength and peak V.O2 were related to age in COPD, particularly in
      women and men with a gas transfer capacity of >50% predicted. Yet, counter to our
      hypothesis, lower-limb lean muscle mass did not show an age-graded reduction and,
      in turn, could not account for the relationship of age with quadriceps strength
      and peak V.O2. CONCLUSIONS: It is apparent that there is an age-graded reduction
      in skeletal muscle function in patients with COPD. Therefore, prevention of an
      age-graded decline in quadriceps muscle strength and peak V.O2 may need to become
      an outcome of pulmonary rehabilitation of patients with COPD.

PMID- 22378476
TI  - Modified constraint-induced movement therapy and modified forced-use therapy for
      stroke patients are both effective to promote balance and gait improvements.
AB  - BACKGROUND: Previous studies show that chronic hemiparetic patients after stroke,
      presents inabilities to perform movements in paretic hemibody. This inability is
      induced by positive reinforcement of unsuccessful attempts, a concept called
      learned non-use. Forced use therapy (FUT) and constraint induced movement therapy
      (CIMT) were developed with the goal of reversing the learned non-use. These
      approaches have been proposed for the rehabilitation of the paretic upper limb
      (PUL). It is unknown what would be the possible effects of these approaches in
      the rehabilitation of gait and balance. OBJECTIVES: To evaluate the effect of
      Modified FUT (mFUT) and Modified CIMT (mCIMT) on the gait and balance during four
      weeks of treatment and 3 months follow-up. METHODS: This study included thirty
      seven hemiparetic post-stroke subjects that were randomly allocated into two
      groups based on the treatment protocol. The non-paretic UL was immobilized for a
      period of 23 hours per day, five days a week. Participants were evaluated at
      Baseline, 1st, 2nd, 3rd and 4th weeks, and three months after randomization. For
      the evaluation we used: The Stroke Impact Scale (SIS), Berg Balance Scale (BBS)
      and Fugl-Meyer Motor Assessment (FM). Gait was analyzed by the 10-meter walk test
      (T10) and Timed Up & Go test (TUG). RESULTS: Both groups revealed a better health
      status (SIS), better balance, better use of lower limb (BBS and FM) and greater
      speed in gait (T10 and TUG), during the weeks of treatment and months of follow
      up, compared to the baseline. CONCLUSION: The results show mFUT and mCIMT are
      effective in the rehabilitation of balance and gait.

PMID- 22378477
TI  - Fall-related factors among less and more active older outpatients.
AB  - BACKGROUND: Fall-related factors in older adults with different levels of
      physical activity, within a multidimensional approach, have not been widely
      investigated. OBJECTIVE: To explore fall-related factors among older adults with
      different physical activity levels. METHODS: A cross-sectional, exploratory study
      with 118 older adult outpatients. Participants who reported at least one fall in
      the previous 12 months were considered fallers. The activity level was assessed
      through the Human Activity Profile. A cutoff of 54 points was used to define the
      less active group and the more active group. A multidimensional questionnaire and
      a set of physical functioning tests were applied. RESULTS: Fall prevalence was
      lower among the more active older adults (47.4%) when compared with the less
      active older adults (71.4%) (p<0.013). Logistic regression analysis showed that,
      among the more active group, falls were associated with: depressive symptoms
      (OR=0.747, 95%CI=0.575-0.970; p=0.029), concern about falling (OR=1.17,
      95%CI=1.072-1.290; p=0.001), and self-selected walking speed (OR=0.030,
      95%CI=0.004-0.244; p=0.001). For the less active group, the model was composed of
      age (OR=1.197, 95%CI=1.032-1.387; p=0.017) and functional disability (OR=14.447,
      95%CI=1.435-145.45; p=0.023). CONCLUSION: For the more active older adults,
      reduced self-efficacy suggests that falling can trigger some protective behavior,
      such as slower gait and depressive symptoms, but the casual link between falls
      and these outcomes should be further investigated. These data emphasize that
      physical therapists should be aware that there are differences in fall-related
      factors depending on the older patients' physical activity level, and this must
      be considered when planning interventions for this population.

PMID- 22378478
TI  - Different instructions during the ten-meter walking test determined significant
      increases in maximum gait speed in individuals with chronic hemiparesis.
AB  - OBJECTIVE: To evaluate the effects of different instructions for the assessment
      of maximum walking speed during the ten-meter walking test with chronic stroke
      subjects. METHODS: Participants were instructed to walk under four experimental
      conditions: (1) comfortable speed, (2) maximum speed (simple verbal command), (3)
      maximum speed (modified verbal command--"catch a bus") and (4) maximum speed
      (verbal command + demonstration). Participants walked three times in each
      condition and the mean time to cover the intermediate 10 meters of a 14-meter
      corridor was registered to calculate the gait speed (m/s). Repeated-measures
      ANOVAs, followed by planned contrasts, were employed to investigate differences
      between the conditions (alpha=5%). Means, standard deviations and 95% confidence
      intervals (CI) were calculated. RESULTS: The mean values for the four conditions
      were: (1) 0.74m/s; (2) 0.85 m/s; (3) 0.93 m/s; (4) 0.92 m/s, respectively, with
      significant differences between the conditions (F=40.9; p<0.001). Comfortable
      speed was significantly slower than the maximum speed, indicating that the
      participants were able to increase speeds when required. Significant differences
      were observed between the second condition with the third (p=0.002; 95%CI=-0.13
      to -0.03) and the fourth conditions (p=0.004; 95%CI=-0.12 to -0.02) with no
      differences between the third and fourth conditions (p=1.00; 95%CI=-0.04 to
      0.05). CONCLUSIONS: The results indicated that simple verbal commands were not
      sufficient to capture maximum gait speed with chronic stroke subjects. Thus, for
      clinical assessments and research purposes, where measurements of the maximum
      gait speed are necessary, modified verbal commands or demonstration strategies
      could be employed by physical therapists to ensure accurate information.

PMID- 22378479
TI  - Initial experience in evaluating the prevalence of unruptured intracranial
      aneurysms detected on 3-tesla MRI.
AB  - BACKGROUND: Given the very poor outcome of ruptured intracranial aneurysms,
      detection and treatment of unruptured intracranial aneurysms by a less invasive
      examination have become important. For this purpose, 3-tesla (3T) magnetic
      resonance imaging (MRI) is the most suitable candidate, owing to its high
      signal/noise ratio and frequency resolution. However, few reports have
      investigated the prevalence of intracranial aneurysms with high-tesla MRI. Here,
      we evaluated the prevalence of intracranial aneurysms and the effectiveness of a
      3T MRI system in their detection. METHODS: During a 1-year period, a total of
      3,414 consecutive patients undergoing MR angiography with 3T MRI for the first
      time were enrolled. Diagnosis of intracranial aneurysm was made by two
      neuroradiologically trained medical doctors under complete blinding to patient
      information. When intracranial aneurysm was suspected, volume-rendering images
      were created for more accurate diagnosis. RESULTS: Surprisingly, 317 unruptured
      intracranial aneurysms were identified in 286 of 3,414 cases (8.4%); 151
      unruptured aneurysms (47.6%) occurred in the internal carotid artery, 85 (26.8%)
      in the middle cerebral artery, 54 (17.0%) in the anterior cerebral artery, and 27
      (8.5%) in the posterior circulation. Of these, 152/317 (47.9%) were <3 mm, 104
      (32.8%) ranged from 3 to 5 mm, 5 (11.0%) from 5 to 7 mm, and 26 (8.2%) were >7
      mm. No significant difference in size was seen among the four locations.
      CONCLUSIONS: For the first time, this study assessed the detection rate of
      intracranial aneurysms using 3T MRI. Results showed a higher detection rate than
      previously documented. The reason for this higher rate is likely the improved
      ability of this modality to detect unruptured aneurysms in the internal carotid
      artery and those <3 mm.

PMID- 22378480
TI  - Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three
      main subtypes of sporadic renal cell carcinoma.
AB  - OBJECTIVES: We studied the role of minor mismatch repair proteins (MMR) human
      MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes
      of renal cell carcinoma (RCC). METHODS: Expression of MMR proteins hMLH1 and
      hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by
      immunohistochemistry. Furthermore, each tumor was screened for microsatellite
      instability (MSI) using the National Cancer Institute consensus panel for
      hereditary non-polyposis colon carcinoma as well as for elevated microsatellite
      alterations at selected tetranucleotide repeats (EMAST) by 10 additional markers.
      RESULTS: MSI was found only in 2.0% of analyzable cases and EMAST was detected
      only in 1 patient. hMLH1 and hMSH2 expression was reduced in 83.7 (118/141) and
      51.2% (65/127) of cases, respectively, in a subtype-specific manner. None of the
      clear cell RCC tumors retained a high hMLH1 expression and 92.0% lost hMLH1
      completely, while papillary and chromophobe RCC preserved the expression in 25.0
      and 33.3% of cases (p < 0.001). Subtype specificity was also present in hMSH2
      staining, where chromophobe RCC retained a high expression in 41.7% of cases,
      while clear cell and papillary tumors did not (29.9 and 23.1%; p = 0.01).
      CONCLUSION: MSI and EMAST are rare events in sporadic RCC, whereas diminished MMR
      protein expression is linked to tumor entity and might contribute to the
      different biological behavior of the RCC subtypes.

PMID- 22378481
TI  - Esterases with an introduced amidase-like hydrogen bond in the transition state
      have increased amidase specificity.

PMID- 22378482
TI  - Predicting the route of delivery in women with low-lying placenta using
      transvaginal ultrasonography: significance of placental migration and marginal
      sinus.
AB  - BACKGROUND/AIMS: To examine the significance of placental migration and the
      presence of a placental marginal sinus to predict the eventual route of delivery
      in low-lying placenta. METHODS: 49 women with a low-lying placenta after 30
      weeks' gestation were studied. The distance between the internal os and leading
      edge of the placenta was measured weekly using transvaginal ultrasonography until
      37 weeks' gestation. The relationship between the rate of placental migration,
      the presence of a placental marginal sinus and the eventual mode of delivery was
      investigated. RESULTS: Although the cesarean section rate was 56.3% (9/16) in the
      'slow' migration (0-2.0 mm/week) group, no patient (0/33) in the 'fast' (>2.0
      mm/week) migration group underwent a cesarean section (p < 0.01). The cesarean
      section rate was 71.4% (5/7) in patients with a placental marginal sinus,
      significantly greater than the rate of 9.5% (4/42) in patients without a marginal
      sinus (p < 0.01). CONCLUSION: A decreased rate of placental migration until 37
      weeks' gestation and the presence of a placental marginal sinus were associated
      with subsequent cesarean delivery because of antepartum vaginal bleeding. These
      parameters may be useful for predicting the route of delivery in women with a low
      lying placenta.

PMID- 22378484
TI  - Highly chemoselective calcium-catalyzed propargylic deoxygenation.
AB  - A calcium-catalyzed direct reduction of propargylic alcohols and ethers has been
      accomplished by using triethylsilane as a nucleophilic hydride source. At room
      temperature a variety of secondary propargylic alcohols was deoxygenated to the
      corresponding hydrocarbons in excellent yields. Furthermore, for the first time,
      a catalytic deoxygenation of tertiary propargylic alcohols was generally
      applicable. The same protocol was suitable for an efficient reduction of
      secondary as well as tertiary propargylic methyl, benzyl and allyl ethers.
      Substrates containing an additional keto-, ester or secondary hydroxyl function
      were reduced with exceptional chemoselectivity at the propargylic position.

PMID- 22378485
TI  - Percutaneous left ventricular assist device with TandemHeart for high-risk
      percutaneous coronary intervention: the Mayo Clinic experience.
AB  - BACKGROUND: In patients with poor left ventricular function and severe left main
      or multivessel coronary disease, coronary artery bypass grafting (CABG) surgery
      has been the preferred therapy. However, a number of these patients are either
      inoperable or poor surgical candidates due to comorbid conditions and previous
      cardiac surgical procedures. These patients are generally poor candidates for
      standard percutaneous coronary intervention (PCI) techniques. A hybrid PCI
      approach with hemodynamic support may be a viable strategy for these patients. We
      report our experience using the TandemHeart percutaneous left ventricular assist
      device during high-risk PCI. METHODS: Retrospective cross-sectional analysis of
      prospectively collected data in 54 patients undergoing high-risk PCI using the
      TandemHeart device for support. Hemodynamic and clinical data were collected and
      analyzed. RESULTS: Baseline clinical characteristics were as follows: mean age 72
      +/- 1.7 years, males 78%, median ejection fraction 20%, mean serum creatinine 1.6
      +/- 0.3 2 mg/dL, recent myocardial infarction 52%, COPD 33%, previous CABG 50%,
      diabetes mellitus 41%, and hypertension 83%. The median SYNTAX score was 33, and
      the median Jeopardy score was 10. The predicted surgical revascularization
      mortality was 13% by the Society for Thoracic Surgery risk score and 33% by
      Euroscore. There was a significant decrease in right and left heart pressures (P
      < 0.05) with a concomitant increase in the cardiac output from 4.7 to 5.7 L/min
      (P = 0.03) during TandemHeart support. Left main and multivessel PCI was
      performed in 62% of patients, and rotablation was used in 48%. Procedural success
      rate was 97%, whereas 30-day and 6 month survival were 90% and 87%, respectively.
      Major vascular complications occurred in 13% of cases. None of our patients
      developed contrast induced nephropathy or needed dialysis. CONCLUSIONS: High-risk
      PCI with percutaneous left ventricular support using TandemHeart is a viable
      therapeutic strategy for a select subset of patients at very high risk with
      standard percutaneous revascularization techniques.

PMID- 22378483
TI  - Association of baseline urodynamic measures of urethral function with clinical,
      demographic, and other urodynamic variables in women prior to undergoing
      midurethral sling surgery.
AB  - AIMS: To explore how baseline demographic, clinical, and urodynamic (UDS)
      variables correlate with measures of urethral function in women planning
      midurethral sling surgery. METHODS: Women with predominant stress urinary
      incontinence (SUI) as part of the trial of mid-urethral slings (TOMUS) were
      characterized preoperatively including: demographics, body mass index (BMI),
      responses to the Medical and Epidemiologic Social Aspects of Aging (MESA) and
      Urogenital Distress Inventory (UDI) questionnaires, pad weight (PW), incontinence
      duration, prior SUI surgery, prolapse, strength of pelvic contraction, Q-tip
      test, uroflow, cystometrogram, and detrusor pressures at maximum flow (Pdet at
      Qmax). Multivariate regression analysis and modeling confirmed variables with
      significant correlations with maximal urethral closure pressure (MUCP),
      functional urethral length (FUL), and Valsalva leak point pressure (VLPP).
      RESULTS: Five-hundred thirty-nine women were included in the analysis. In
      multivariable analyses, PW (P =  0.045) and age (P < 0.0001) were negatively
      correlated with MUCP (as PW and age increased, MUCP decreased); BMI (P = 0.02)
      and Pdet at Qmax (P < 0.0001) were positively correlated with MUCP (as BMI and
      Pdet at Qmax increased, MUCP increased). Age (P = 0.002) was negatively
      correlated with FUL; Qtip delta (P = 0.006), pelvic organ prolapse quantification
      examination (POPQ) stage (P = 0.002) and strength of pelvic contraction (P =
      0.03) were positively correlated with FUL. Duration of incontinence (P = 0.01)
      was negatively correlated with VLPP; Qtip delta (P = 0.02), BMI (P = 0.0005) and
      Pdet at Qmax (P = 0.0005) were positively correlated with VLPP. CONCLUSIONS: Age,
      BMI, Qtip delta, and Pdet at Qmax were variables that correlated with two or more
      measures of urethral function. These correlations may help direct future research
      in female urethral function.

PMID- 22378486
TI  - Synthesis of alpha-fluoro-beta-hydroxy esters by an enantioselective Reformatsky
      type reaction.
AB  - The first enantioselective Reformatsky-type reaction of ethyl iodofluoroacetate
      has been accomplished with alkyl aryl ketones. High diastereoselectivities and
      excellent enantioselectivities for the major diastereomer (93-95% ee) were
      achieved with large alkyl groups. For smaller alkyl groups the
      diastereoselectivities were moderate, but excellent enantioselectivities were
      obtained for both diastereomers (79-94% ee).

PMID- 22378487
TI  - PDEF downregulates stathmin expression in prostate cancer.
AB  - The Ets proteins are a family of transcription factors characterized by an
      evolutionarily conserved DNA binding domain that controls key cellular processes.
      Prostate-derived Ets transcription factor (PDEF), a member of the Ets family, is
      reported to be present in tissues with high epithelial content, notably breast
      and prostate. However, the role of PDEF in cancer development is not fully
      understood. To gain insight into the molecular mechanisms associated with
      prostate cancer progression, we employed iTRAQ labeling followed by mass
      spectrometric (MS) analysis to identify candidate proteins that are
      differentially expressed in prostate cancer cells with or without PDEF. To this
      end, we overexpressed PDEF in PC3 human prostate cells using a tetracycline
      inducible system (Tet-On). Many differentially expressed proteins which play
      important roles in various cellular and biological processes were identified.
      Among them, stathmin (STMN), which is a microtubule (MT)-destabilizing protein,
      was found to be downregulated in multiple analyses. We demonstrated that re
      expression of STMN reversed the antitumor properties of PDEF in PDEF
      overexpressing PC3 cells. Using in vitro functional assays, we showed that STMN
      overexpression counteracted PDEF's effects against cell proliferation, colony
      formation and tumor migration. Similar results were further confirmed with the
      prostate cancer cell line CWR22rv1. In conclusion, many differentially expressed
      proteins were identified and STMN was found to be downregulated by PDEF. These
      results suggest that PDEF may inhibit prostate cancer progression by
      transcriptional downregulation of oncogenic STMN expression. Analyzing the
      association among differentially expressed proteins may provide a basis to better
      understand the molecular mechanisms underlying the process of cancer progression
      and development and further aid in designing therapeutics in the future.

PMID- 22378488
TI  - Telmisartan improves cardiometabolic profile in obese patients with arterial
      hypertension.
AB  - OBJECTIVE: There are several lines of evidence that telmisartan may improve
      cardiometabolic profile. The aim of the study was to estimate changes of insulin
      resistance and plasma concentrations of adipokines after long-term
      antihypertensive treatment with telmisartan in obese hypertensive patients.
      METHODS: 34 previously untreated obese adults with arterial hypertension were
      enrolled. Glucose cellular uptake (M value) and the M to insulin ratio (M/I
      value) were measured by euglycemic-hyperinsulinemic clamp technique, body fat
      content (by dual-energy X-ray absorptiometry method), as well as plasma
      concentrations of selected adipokines and cytokines were estimated before and
      after 6-month telmisartan therapy in 25 patients who completed the study.
      RESULTS: Telmisartan therapy was followed by 14.2% decrease of systolic and by
      19.6% decrease of diastolic blood pressure. Body fat mass did not change
      significantly. Both M and M/I values (by 24.4 and by 38.6%, respectively) as well
      as plasma levels of total and high-molecular-weight adiponectin (by 10.8 and by
      23.5%, respectively) increased significantly. Plasma concentrations of high
      sensitivity C- reactive protein and interleukin-8 decreased significantly, while
      those of interleukin-6 and tumor necrosis factor-alpha tended to decline.
      CONCLUSIONS: Telmisartan monotherapy improves cardiometabolic profile in obese
      hypertensive patients by improving insulin sensitivity and increasing of plasma
      adiponectin concentration, including its high-molecular-weight fraction, and by
      suppressing of microinflammation.

PMID- 22378491
TI  - Structural determination of NSC 670224, synthesis of analogues and biological
      evaluation.
AB  - Follow my lead! NSC 670224, previously shown to be toxic to Saccharomyces
      cerevisiae at low micromolar concentrations, potentially acts via a mechanism of
      action related to that of tamoxifen (NSC 180973), breast cancer drug. The
      structure of NSC 670224, previously thought to be a 2,4-dichloro arene, was
      established as the 3,4-dichloro arene, and a focused library of analogues were
      synthesized and biologically evaluated.

PMID- 22378492
TI  - Cooperation of Epac1/Rap1/Akt and PKA in prostaglandin E(2) -induced
      proliferation of human umbilical cord blood derived mesenchymal stem cells:
      involvement of c-Myc and VEGF expression.
AB  - Prostaglandin E(2) (PGE(2)) is well known to regulate cell functions through
      cAMP; however, the role of exchange protein directly activated by cAMP (Epac1)
      and protein kinase A (PKA) in modulating such functions is unknown in human
      umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Therefore, we
      investigated the relationship between Epac1 and PKA during PGE(2)-induced hUCB
      MSC proliferation and its related signaling pathways. PGE(2) increased cell
      proliferation, and E-type prostaglandin (EP) 2 receptor mRNA expression level and
      activated cAMP generation, which were blocked by EP2 receptor selective
      antagonist AH 6809. PGE(2) increased Epac1 expression, Ras-related protein 1
      (Rap1) activation level, and Akt phosphorylation, which were inhibited by AH
      6809, adenylyl cyclase inhibitor SQ 22536, and Epac1/Rap1-specific siRNA. Also,
      PGE(2) increased PKA activity, which was inhibited by AH 6809, SQ 22536, and PKA
      inhibitor PKI. HUCB-MSCs were incubated with the Epac agonist 8-pCPT-cAMP or the
      PKA agonist 6-phe-cAMP to examine whether Epac1/Rap1/Akt activation was
      independent of PKA activation. 8-pCPT-cAMP increased Akt phosphorylation but not
      PKA activity. 6-Phe-cAMP increased PKA activity, but not Akt phosphorylation.
      Additionally, an Akt inhibitor or PKA inhibitor (PKI) did not block the PGE(2) 
      induced increase in PKA activity or Akt phosphorylation, respectively. Moreover,
      PGE(2) increased glycogen synthase kinase (GSK)-3beta phosphorylation and nuclear
      translocation of active-beta-catenin, which were inhibited by Akt inhibitor
      or/and PKI. PGE(2) increased c-Myc and vascular endothelial growth factor (VEGF)
      expression levels, which were blocked by beta-catenin siRNA. In conclusion,
      PGE(2) stimulated hUCB-MSC proliferation through beta-catenin-mediated c-Myc and
      VEGF expression via Epac/Rap1/Akt and PKA cooperation.

PMID- 22378493
TI  - Neural integration of speech and gesture in schizophrenia: evidence for
      differential processing of metaphoric gestures.
AB  - Gestures are an important component of interpersonal communication. Especially,
      complex multimodal communication is assumed to be disrupted in patients with
      schizophrenia. In healthy subjects, differential neural integration processes for
      gestures in the context of concrete [iconic (IC) gestures] and abstract sentence
      contents [metaphoric (MP) gestures] had been demonstrated. With this study we
      wanted to investigate neural integration processes for both gesture types in
      patients with schizophrenia. During functional magnetic resonance imaging-data
      acquisition, 16 patients with schizophrenia (P) and a healthy control group (C)
      were shown videos of an actor performing IC and MP gestures and associated
      sentences. An isolated gesture (G) and isolated sentence condition (S) were
      included to separate unimodal from bimodal effects at the neural level. During IC
      conditions (IC > G ? IC > S) we found increased activity in the left posterior
      middle temporal gyrus (pMTG) in both groups. Whereas in the control group the
      left pMTG and the inferior frontal gyrus (IFG) were activated for the MP
      conditions (MP > G ? MP > S), no significant activation was found for the
      identical contrast in patients. The interaction of group (P/C) and gesture
      condition (MP/IC) revealed activation in the bilateral hippocampus, the left
      middle/superior temporal and IFG. Activation of the pMTG for the IC condition in
      both groups indicates intact neural integration of IC gestures in schizophrenia.
      However, failure to activate the left pMTG and IFG for MP co-verbal gestures
      suggests a disturbed integration of gestures embedded in an abstract sentence
      context. This study provides new insight into the neural integration of co-verbal
      gestures in patients with schizophrenia.

PMID- 22378494
TI  - Addition of sucralose enhances the release of satiety hormones in combination
      with pea protein.
AB  - SCOPE: Exposing the intestine to proteins or tastants, particularly sweet,
      affects satiety hormone release. There are indications that each sweetener has
      different effects on this release, and that combining sweeteners with other
      nutrients might exert synergistic effects on hormone release. METHODS AND
      RESULTS: STC-1 cells were incubated with acesulfame-K, aspartame, saccharine,
      sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation
      period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations
      were measured. Using Ussing chamber technology, the mucosal side of human
      duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each
      sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1
      cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose
      increased CCK levels, whereas GLP-1 levels increased after addition of all test
      products. Addition of sucrose and sucralose to human duodenal biopsies did not
      affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion.
      CONCLUSION: Combining pea with sucrose and sucralose induced even higher levels
      of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine
      cells induced higher levels of CCK and GLP-1 than addition of each compound
      alone. This study shows that combinations of dietary compounds synergize to
      enhance satiety hormone release.

PMID- 22378495
TI  - High-performance broadband photodetector using solution-processible PbSe-TiO(2)
      graphene hybrids.
AB  - Highly sensitive, multicomponent broadband photodetector devices are made from
      PbSe/graphene/TiO(2). TiO(2) and PbSe nanoparticles act as light harvesting
      photoactive materials from the UV to IR regions of the electromagnetic spectrum,
      while the graphene acts as a charge collector for both photogenerated holes and
      electrons under an applied electric field.

PMID- 22378496
TI  - Psychological interventions for delayed ejaculation/orgasm.
AB  - Of all the male sexual dysfunctions, delayed ejaculation (DE) is the least
      understood, least common and least studied. This paper aims to review and
      integrate the diverse psychological theories and proposed psychological
      interventions for DE. Clinicians will then be able to more clearly discern the
      relevant psychological/interpersonal issues of the patient/couple and implement
      systematically based effective interventions. After reviewing the literature, it
      is clear that no one theory accounts for all the varied presentations of DE, and
      no theory by itself has strong empirical support. However, awareness of the
      diverse points of view helps clinicians conduct better assessments and broaden
      their understanding of the patient's ejaculatory dysfunction. Similarly, no one
      psychological intervention works for all patients, nor will unsystematic random
      selection of interventions. This paper stresses on the need to clearly identify
      the source of the dysfunction and select treatments based upon the precipitating
      and maintaining factors. Much work remains to be done with regard to our
      understanding and treatment of DE. Specifically, we need to craft an evidence
      based definition, assess the true prevalence of the dysfunction, demonstrate the
      efficacy of psychological interventions and design validated outcome measures.

PMID- 22378497
TI  - Transcriptional profile of native CD271+ multipotential stromal cells: evidence
      for multiple fates, with prominent osteogenic and Wnt pathway signaling activity.
AB  - OBJECTIVE: Controversy surrounds the identity and functionality of rare bone
      marrow-derived multipotential stromal cells (BM-MSCs), including their
      differentiation capabilities, their relationship to pericytes and hematopoiesis
      supporting stromal cells, and the relevance of their culture-expanded progeny in
      studies of skeletal biology and development of cell-based therapies. The aim of
      this study was to clarify the nature of candidate BM-MSCs by profiling
      transcripts that reflect different aspects of their putative functions in vivo.
      METHODS: Rare, sorted BM-derived CD45(-/low) CD271(bright) (CD271) cells were
      analyzed using 96-gene expression arrays focused on transcripts relevant to
      mesenchymal-lineage differentiation (toward bone, cartilage, fat, or muscle),
      hematopoietic and stromal support, and molecules critical to skeletal
      homeostasis. These cells were compared to matched CD45+ CD271- hematopoietic
      lineage cells, culture-expanded MSCs, and skin fibroblasts. When feasible,
      transcription was validated using flow cytometry. RESULTS: CD271 cells had a
      transcriptional profile consistent with the multiple fates of in vivo MSCs,
      evident from the observed simultaneous expression of osteogenic, adipogenic,
      pericytic, and hematopoiesis-supporting genes (e.g., SP7 [osterix], FABP4 [fatty
      acid binding protein 4], ANGPT1 [angiopoietin 1], and CXCL12 [stromal cell
      derived factor 1], respectively). Compared to culture-expanded MSCs and
      fibroblasts, CD271 cells exhibited greater transcriptional activity, particularly
      with respect to Wnt-related genes (>1,000-fold increased expression of FRZB
      [secreted frizzled-related protein 3] and WIF1 [Wnt inhibitory factor 1]). A
      number of transcripts were identified as novel markers of MSCs. CONCLUSION: The
      native, BM-derived in vivo MSC population is endowed with a gene signature that
      is compatible with multiple functions, reflecting the topographic bone niche of
      these cells, and their signature is significantly different from that of culture
      expanded MSCs. This indicates that studies of the biologic functions of MSCs in
      musculoskeletal diseases, including osteoporosis and osteoarthritis, should focus
      on in vivo MSCs, rather than their culture-adapted progeny.

PMID- 22378498
TI  - Donation after cardiac death liver transplantation: lose a bit on each one and
      make it up in volume.

PMID- 22378499
TI  - Factors associated with caregivers' underestimation of quality of life in
      patients with Alzheimer's disease.
AB  - OBJECTIVE: The aim of this study was to identify the factors associated with
      differences between how Alzheimer's disease (AD) patients and their caregivers
      rate the patient's health-related quality of life (QoL). METHODS: Cross
      sectional, multicentre study. Patients were 65 years or more, suffering from mild
      to moderate AD, native French speakers, with a main caregiver. Interrater
      agreement of the QoL-AD was assessed using the intraclass coefficient. A
      generalised linear model was used to identify factors related to the difference
      in health-related QoL scores between patients and their caregivers. RESULTS: The
      122 patients of the study were 82 +/- 6 years old and mainly women (69%).
      Independent factors related to the difference between patients and caregivers
      were: Mini Mental State Exam score (beta = 0.32; 95% CI = 0.05-0.59);
      instrumental activities of daily living score (beta = -0.61; 95% CI = -1.14 to 
      0.07); total Neuropsychiatric Inventory score (beta = 0.10; 95% CI = 0.05-0.59),
      and Zarit's burden score (beta = 0.09; 95% CI = 0.01-0.17). CONCLUSION:
      Practitioners must take into account the trend towards underestimation when
      health-related QoL is rated by caregivers or proxies.

PMID- 22378500
TI  - Successful surgical excision of a nondysraphic holodorsal intramedullary lipoma
      in a 14-month-old child.
AB  - INTRODUCTION: Nondysraphic intramedullary lipomas of the spinal cord are rare
      lesions. They are most commonly seen in the second or third decade of life. Their
      occurrence in the pediatric age group is even rarer. CASE REPORT: The authors
      describe a 14-month-old child who presented with delayed motor milestones
      involving the bilateral lower limbs. The child was unable to sit or stand. MRI
      revealed a dorsally located intramedullary lipoma extending from C7 to D12. The
      child underwent C7-L1 laminotomy and gross total excision of the lipoma.
      Postoperatively, the child improved neurologically and attained normal power in
      the bilateral lower limbs. DISCUSSION: Very few cases of extensive intramedullary
      lipomas involving the dorsal cord have previously been reported. Only two cases
      of pediatric extensive dorsal lipomas have been mentioned to date. The authors
      describe successful surgical excision of a holodorsal intramedullary lipoma in a
      14-month-old child. To the best of the authors' knowledge, this is the first case
      being reported of a holodorsal intramedullary lipoma in the youngest patient.

PMID- 22378501
TI  - A general and efficient palladium-catalyzed alkoxycarbonylation of phenols to
      form esters through in situ formed aryl nonaflates.

PMID- 22378502
TI  - Residual methylprednisolone suppresses human T-cell responses to spleen, but not
      islet, extracts from deceased organ donors.
AB  - Pancreatic islets, transplanted into recipients with type 1 diabetes, are exposed
      to allogenic and auto-immune T-cell responses. We set out to develop an assay to
      measure these responses using PBMC. Our approach was to prepare spleen extract
      from the islet donors (allo-antigen) and islet extracts (auto-antigen). To our
      surprise, we found that spleen extracts potently inhibited the proliferation of
      human T cells driven by antigen (tetanus toxoid) and mitogen (anti-CD3 mAb,
      OKT3), whereas extracts prepared from pancreatic islets from the same donor did
      not suppress T-cell proliferation. Suppression mediated by spleen extracts was
      unaffected by blocking mAbs against the IL-10R, transforming growth factor-beta
      or CD152 (CTLA-4). It was also unaffected by denaturing the spleen extracts by
      heating, exposing to reducing agents or protease digestion. Because deceased
      organ donors are commonly given the immunosuppressive glucocorticoid
      methylprednisolone prior to death, we hypothesized that suppression was due to
      residual methylprednisolone in the spleen extracts. Methylprednisolone could be
      detected by mass spectrometry in spleen extracts at concentrations that suppress
      T-cell proliferation. Finally, the glucocorticoid receptor antagonist
      mifepristone completely reversed the suppression caused by the spleen extracts.
      We conclude that extracts of human spleen, but not islets, from deceased organ
      donors contain sufficient residual methylprednisolone to suppress the
      proliferation of T-cells in vitro.

PMID- 22378504
TI  - Uranium series radionuclides in surface waters from the Shu river (Kazakhstan).
AB  - The concentrations of (238)U, (234)U, (226)Ra, (210)Po and (210)Pb have been
      determined in surface waters collected along the course of the Shu River, lying
      on the border between Kazakhstan and Kyrgyzstan. In the study area, the river
      runs through some of the largest uranium deposits worldwide, which were actively
      exploited during the nuclear weapons and nuclear energy programmes of the former
      Soviet Union. The data show an increasing trend in uranium concentrations
      downstream the river from the city of Tokmak to the city of Shu, with good
      correlation between total uranium concentrations and total dissolved solids. Data
      on uranium isotopes disequilibrium show the presence of technogenic uranium
      inputs into the Shu River downstream from the city of Karasu, evidenced by a
      decrease in the measured (234)U/(238)U isotopic ratio from 1.63 in uncontaminated
      sites to 1.29 in sites affected by past mining activities.

PMID- 22378503
TI  - EF24 suppresses maturation and inflammatory response in dendritic cells.
AB  - Synthetic curcuminoid EF24 was studied for its effect on the maturation and
      inflammatory response in murine bone marrow derived immortalized JAWS II
      dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II,
      CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical
      characteristic of mature DCs. These effects were accompanied by the inhibition of
      LPS-induced activation of transcription factor nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB). Simultaneous reduction of pro
      inflammatory cytokines [tumor necrosis factor (TNF)-alpha, IL-6] both at the mRNA
      and secreted levels was also observed. To investigate the dependency of LPS
      effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant
      negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-kappaB activity and
      TNF-alpha secretion in a MyD88-dependent manner. These results suggest that EF24
      modulates DCs by suppressing their maturation and reducing the secretion of
      inflammatory cytokines. Further, it appears that EF24 acts at or upstream of
      MyD88 in the LPS-TLR4/MyD88/NF-kappaB pathway.

PMID- 22378505
TI  - Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic
      pathway in human lung adenocarcinoma cells.
AB  - This report is designed to explore the exact molecular mechanism by which
      artesunate (ART), a semisynthetic derivative of the herbal antimalaria drug
      artemisinin, induces apoptosis in human lung adenocarcinoma (ASTC-a-1 and A549)
      cell lines. ART treatment induced ROS-mediated apoptosis in a concentration- and
      time-dependent fashion accompanying the loss of mitochondrial potential and
      subsequent release of Smac and AIF indicative of intrinsic apoptosis pathway.
      Blockage of casapse-8 and -9 did not show any inhibitory effect on the ART
      induced apoptosis, but which was remarkably prevented by silencing AIF. Of the
      utmost importance, ART treatment induced the activation of Bak but not Bax, and
      silencing Bak but not Bax remarkably inhibited ART-induced apoptosis and AIF
      release. Furthermore, although ART treatment did not induced a significant down
      regulation of voltage-dependent anion channel 2 (VDAC2) expression and up
      regulation of Bim expression, silencing VDAC2 potently enhanced the ART-induced
      Bak activation and apoptosis which were significantly prevented by silencing Bim.
      Collectively, our data firstly demonstrate that ART induces Bak-mediated caspase
      independent intrinsic apoptosis in which Bim and VDAC2 as well as AIF play
      important roles in both ASTC-a-1 and A549 cell lines, indicating a potential
      therapeutic effect of ART for lung cancer.

PMID- 22378506
TI  - (Re) creation and innovation of nursing care.

PMID- 22378507
TI  - [The Unified Health System in the users' social representation: an analysis of
      its structure].
AB  - The objective of this study was to analyze the representational structure of a
      group of users of the Unified Health System (SUS) in the city of Rio de Janeiro,
      Brazil, concerning the system. A qualitative research, grounded on the theory of
      the central nucleus of the social representations, was developed with 104 users
      of five health care facilities. Data were collected through the free evocation to
      the inducer term SUS, and analyzed by the software EVOC 2000. The structure of
      the representation disclosed four dimensions: conceptual, evaluative, spatial,
      and finalistic. They presented, respectively, the following lexicons in their
      central nucleus: health, well attended, hospital and attendance. Negative
      elements of contrast were found amidst the positive representation of the system
      and the presence of all four dimensions was observed in the periphery, with
      predominance of the finalistic one. The conclusion is that the system presents
      itself to the citizens in a pragmatic way and that its implementation is still
      necessary.

PMID- 22378508
TI  - [Environmental pollution, maternal residence and low birth weight].
AB  - Case-control study, which aimed to analyze the risk factors associated with low
      birth weight of newborns of mothers from Rio Grande-RS that resided in the
      proximities of the industrial area. Mothers that gave birth in the maternities of
      the municipality were interviewed during the months of April to November of 2003.
      The sample comprehended 138 cases and 409 controls. It was performed the
      bivariate and multivariate statistical analysis. The Low Birth Weight (LBW)
      maintained itself positively associated with previous stillborns, previous LBWs,
      the presence of arterial hypertension during the pregnancy, and the threat of
      abortion during the current pregnancy. It was possible to identify the main
      factors of risk to which pregnant women are exposed and that interfere with birth
      weight of their children, which are in addition to those resulting from a greater
      exposure to pollutants, because they live near the industries.

PMID- 22378509
TI  - [I-THOU Eternal relationship in the life of caregivers of children with AIDS:
      study based on Martin Buber philosophy].
AB  - This phenomenological study aimed at understanding, in the light of Martin
      Buber's philosophy, what is to be a caregiver of children with AIDS. The
      phenomenological interview guided the meeting with seven caregivers of children
      with AIDS, selected in a teaching hospital of Porto Alegre-RS, southern of
      Brazil. The data were interpreted in the light of hermeneutics, emerging the unit
      of meaning Dialogues 'between' the familiar I and the Eternal THOU. The dialogues
      take place in the search for answers that allow the understanding of the
      significance of the impact and challenges they face while living with AIDS. As
      well, they reveal hope in changes, in the cure and in a vaccine development. We
      believe that knowing the importance of dialogue in the context of HIV/AIDS
      epidemic provide the development of a nursing care that brings together the
      technical-scientific and humanistic aspects.

PMID- 22378510
TI  - [The (un)said about AIDS in the quotidian transition from childhood to the
      adolescence].
AB  - HIV children infected by vertical transmission are crossing from childhood to
      adolescence, however, we do not know how they are caring for themselves during
      those transitional age. The objective was to understand the (un)said about AIDS
      in their quotidian. After approval by the Research Ethics Committee of three
      hospitals in Rio de Janeiro, the interview was conducted with eleven boys/girls
      from 12-14 years old, who knew their diagnosis. The Heideggerian hermeneutics
      unveiled that the adolescent-being knows that the disease was acquired by his/her
      mother; he/she was said that his/her relatives are sick; he/she reminds when the
      diagnosis was disclosure, and its relation to prejudice. He/she projects him/her
      as a being-of-possibilities inside an existential movement. One concludes that
      the care for adolescent-being needs to integrate the biological, clinical, socio
      cultural, ethical, political, and existential dimensions.

PMID- 22378511
TI  - [Reported violence: occurrences of maltreatment against children and adolescents
      registered in a police unit].
AB  - This study aimed to investigate the profile of the occurrence of abuse against
      children and adolescents. We analyzed the data recorded in police reports from
      the Department of Women's Defense, Aracatuba-SP, in 2008, relating to assault,
      victim-offender relationship, sociodemographic characteristics of offenders and
      victims, and victims' demand for health services. Among the accusations, there
      was a higher prevalence of physical abuse, being the residence the place of
      higher incidence of aggression. In most cases, the aggressor was the mother of
      the child, being the subject of aggression not reported, in most cases. Thus, we
      can define the profile of violent incidents against children, contributing to the
      visualization, knowledge and to deal with the problem.

PMID- 22378512
TI  - [Nursing diagnoses for patients at risk of developing pressure ulcer].
AB  - This cross-sectional study aimed to identify nursing diagnoses in critical
      patients at risk of developing pressure ulcer. It was carried out at an Intensive
      Care Unit in Fortaleza-CE, Brazil, using an intentional sample of thirteen
      subjects at risk of pressure ulcer, evaluated according to the Waterlow scale. In
      total, 45 nursing diagnoses were evidenced, seventeen of which were clinically
      significant for the development of pressure ulcer. The frequency levels for nine
      of these nursing diagnoses were >= 80%, mainly: Impaired skin integrity (100%),
      Impaired walking (87%), Impaired swallowing (80%), Impaired bed mobility (80%)
      and Impaired gas exchange (80%). The knowledge of those nursing diagnoses is
      important in detecting the effects and clinical basis of skin lesions.

PMID- 22378513
TI  - [Interpersonal competence in caring of people with diabetes: perception of
      nurses].
AB  - This is a qualitative and exploratory study which aimed to apprehend the
      perceptions of nurses who care for people with Diabetes on the interpersonal
      competence. The subjects were eleven nurses who performed their activities in the
      Units of Family Health in the urban area, and completed a consent form. The data,
      obtained through semi-structured interview, were analyzed and categorized by
      thematic analysis. The results showed that nurses perceive the interpersonal
      competence as an ability to interact with the patient, as the establishment of an
      effective interpersonal relationship and as forms of interpersonal relationships.
      It appeared that the exercise of that power is not subject to standardization,
      what emphasizes the uniqueness of the processes of interaction and of health
      care.

PMID- 22378514
TI  - [Quality of nursing care in intensive therapy: evaluation through operational
      auditing].
AB  - This study aimed to evaluate the quality of nursing care of an Adult Intensive
      Care Unit. Data from fifty in-hospital patients, who stayed in ICU for more than
      three days, were collected through observation, physical examination and
      patients' medical-information records analysis, using an Operational Auditing
      Plan. Care considered of quality were those that obtained positive answer
      percentage >= 70%, as those related to Physical Safety (71%) and Equipment Use
      (72%). Physical Activity (28%) and Oxygenation/Ventilation (29%) reached the
      lowest scores. We concluded that is urgent to implement continuing education
      actions in the service studied, since most care items and sub-items did not
      present the quality needed.

PMID- 22378515
TI  - [Therapeutic communication in Nursing: difficulties for the care of elderly
      people with cancer].
AB  - The objective of this study is to assess the difficulties and their causes, in
      the perception of nurses, to give aid to the old patient bearer oncologic
      pathology. The study, descriptive, used The Critical Incident Technique to the
      obtaining and analyzing of data, complied with the ethical. The subjects were
      nurses, guests, employees of units of cancer care to people aged over 60 years
      and working in oncology for more than a year. The subjects cited 25 critical
      incidents, while 9 situations generated negative feelings, 3 positives and 13
      with double feelings. It was concluded that nurses who reported interventions of
      human character, showed positive feelings, recognizing how important their
      nursing actions were important to offer human assistance.

PMID- 22378516
TI  - [Actions of nurses in a psychiatric hospitalization unit at a university
      hospital].
AB  - Nursing care in mental health has been undergoing a process of paradigmatic
      change, from the asylum model to the pychosocial support. The aim of this study
      is to identify nurses' practices in a psychiatric ward in a university hospital.
      An exploratory and descriptive study of qualitative approach was conducted. Semi
      structured interviews were used to collect data. The results showed the
      apprehension of new concepts to guide mental health care: embracement,
      comprehensive care and individual consideration of the users' subjectivity guided
      nurses' practices. These practices are permeated by issues that go beyond the
      biological aspects, and include family and society.

PMID- 22378517
TI  - [Knowledge and attitudes of workers from a public emergency service about the
      adoption of standard precautions].
AB  - The aims of the study were to evaluate the adoption of the precaution measures,
      assessing knowledge and attitude of multiprofessional team. This is a transversal
      study, accomplished in an Emergency Medical Service of Minas Gerais. Univariate
      and multivariate analysis were used. The results showed that nurses and drivers
      had the highest and lowest level of knowledge regarding the standard precautions,
      respectively. The possibility of non-adoption of the precautionary measures was
      3.76 (95% CI: 1.48 to 9.53) times higher among professionals aged over 31 years
      and 6.7 (95% CI: 1.81 to 24,75) times greater among workers in crowded unit of
      basic support. The conclusion is that is essential to implement strategies in
      order to improve the professional's knowledge related to infection control and
      safety recommendations.

PMID- 22378518
TI  - [Inclusive education policy: perceptions of managers about the process of changes
      in Higher Education Institutions].
AB  - This is a qualitative descriptive exploratory study, conducted in Higher
      Education Institutions (HEI) which offers Nursing course, in Joao Pessoa-PB. The
      study aimed to understand the concept of managers about the need for
      organizational changes to attend customers with special needs. Four managers
      participated in the study. A semi-structured interview with guiding questions was
      used to collect information and to interpret the data we used the method of
      discourse analysis based on Fiorin. It was noticed that the managers have a
      concern to meet the demands of inclusive policies, including the adequacy of
      physical spaces and the pedagogy adopted to meet the students' needs. However,
      some of them admitted to have little knowledge on how to deal with students with
      special needs and also mentioned that the institutions do not have an efficient
      and logistic work which can meet the current legislation of inclusion. We
      concluded that the process of structural and pedagogical changes is built in a
      slow and gradual way and it requires an involvement of qualified managers who are
      committed to execute the policies of inclusion of customers with special needs in
      a civil and legal way.

PMID- 22378519
TI  - [Theory-practice unit in an integrated curriculum praxis: nursing teachers'
      perception in children and teenagers' health].
AB  - The study aimed to understand Nursing teachers' perception about the theory
      practice relation experienced in Nursing education on children and adolescents'
      health, in an integrated curriculum. A qualitative and descriptive study was
      developed, grounded on Vazquez, Freire and Bakhtin's theoretical models.
      Unstructured interviews were used to collect data. Discourse analysis unveiled
      the following categories: Nursing education based on interdisciplinary
      approaches; child care teaching in the context of family health, in different
      settings of care; teachers' praxis engendering a dialectical movement of theory
      and practice. Approaches for Nursing education are pointed out in order to
      support teaching practice and rethink the strategies adopted to integrate theory
      and practice in pedagogical projects.

PMID- 22378520
TI  - [The meaning of the profession to students beginning a Nursing undergraduate
      course].
AB  - This qualitative study aimed to describe the meaning of the profession to
      beginners in a Nursing undergraduate course. A structured interview was
      administered to 33 students of the first semester in a public university in Rio
      de Janeiro, in 2006. Ethical principles were respected. The thematic analysis
      revealed that, when entering the profession, the students visualize nurses as the
      professional who takes care of clients, in a restricted view of care, and
      associate Nursing practice to situations of dedication, care and love. Clarify
      high school students about Nursing, the labor market and Nursing areas of action
      could stimulate the search of the profession by people more conscious about their
      choice.

PMID- 22378521
TI  - [Nursing care during the preoperative stage and rehabilitation of mastectomy:
      narrative review of literature].
AB  - This is a bibliographic research carried out in Lilacs and Scielo database, which
      aimed to review the production about nursing care during the preoperative and
      rehabilitation stages of mastectomy. Eighteen articles were analyzed with focus
      in these categories: Nursing care in the preoperative mastectomy and The role of
      nursing in the rehabilitation of women submitted to a mastectomy. It was observed
      that nursing cares, in the two periods, are a key step for a more human
      treatment. However, they are scarce and with little enlightening guidance there
      must be a greater focus on the role by the nursing team in relation to women
      care.

PMID- 22378522
TI  - [Health advocacy in child care: literature review].
AB  - This narrative literature review aimed to identify the publications about health
      law, in the ambit of child health care. The databases LILACS and MEDLINE were
      searched, between 2004 and 2009. Thirteen articles were analyzed, and three
      themes were identified: Emphasis on knowledge, abilities and attitudes for the
      development of competencies; Partnerships as an imperative; Health and Law:
      intersectorial relationship. The studies about the practice of health law are
      relevant to our reality, especially in primary health care, pointing out for the
      possibilities of its applicability in the role of the nurses acting in the family
      health strategy, with families and children.

PMID- 22378523
TI  - [Adverse events in pediatric pharmacotherapy: integrative literature review].
AB  - This paper is about an integrative review from literature realized in databases
      online, into the period among 2003-2009, with the objective of identify the
      available evidence on the main drug-related adverse events in pediatric clientele
      and propose strategies for reducing them. The study revealed the inadequacy of
      the drugs presentation to meet the specific therapeutic needs of children. It is
      understood that the nurse's decision making about safe preparation and
      administration of drugs should be based on careful and individualized assessment
      of each client. It is therefore necessary that the professional be scientifically
      supported, to implement effective interventions that are able to reduce and even
      prevent adverse events from the uni or polypharmacy.

PMID- 22378524
TI  - [Investigating the production of the knowledge on the long-lived elderly person].
AB  - This paper is a bibliographic review, with quantitative approach, that aimed to
      investigate the production of the knowledge on the long-lived elderly person, in
      the SCIELO and LILACS data bases. Eighty eight scientific papers were analyzed,
      from which 69,3% were produced in Brazil, concentrated in the Southeastern area
      (67,2%), and with prevalence of the qualitative approach (77,3%). As for the
      knowledge area, all the researches are part of the great area of Health Sciences,
      with prevalence of Medicine (76,1%). Nursing contributed with 4,5% of the
      productions. The more studied objects (72,7%) were clinical cases or report of
      experiences. One concluded that the scientific production on long-lived elderly
      person is still small and irrelevant. In this optics, it is essential to increase
      and qualify the productions and the knowledge fields that address this thematic
      universe.

PMID- 22378525
TI  - [Nursing care to the client with hypertension: a bibliographic review].
AB  - This study aimed to identify the nursing care practices to the client with
      hypertension in the scientific production in the last ten years. It was carried
      out a bibliographic study, using in the BIREME, the LILACS, SciELO and BDENF's
      data basis, selecting thirty articles. The results were exposed in charts, tables
      and graphics, where prevails, in the literature analyzed, the nursing
      consultation as the more used practice, through the nursing attendance
      systematization and the Health Education with individual approaches, besides the
      realization of home visits with family approach. One believes that the
      systematization of nursing care will contribute in an expressive manner to the
      adhesion to the antihypertensive treatment.

PMID- 22378526
TI  - [Brazilian literature on nursing work founded on marxist categories].
AB  - This article discusses the Brazilian scientific literature on nursing work based
      on Marxist categories, with the aim of investigating their contributions and
      tendencies. The study is a quanti-qualitative review of 97 articles published
      between 1981 and 2008, indexed in the LILACS. It is discussed: number and
      periodical distribution; themes; methodological and conceptual approaches. It was
      identified: a growing body of literature on nursing especially from 2000 onwards;
      the growth of approaches on the subjects, their perceptions and social
      interaction; the incorporation recently into the debate on caring and nursing
      care management; the predominance of qualitative research and, from the 1990s
      onwards, the incorporation of concepts from other theoretical paths linked to
      Marxists categories. There was evidence of a search for understanding of the
      movements, contradictions and dilemmas in nursing as a heterogeneous social
      practice.

PMID- 22378527
TI  - [Research with families of people with mental disorder].
AB  - The purpose of this paper is to present a critical reflection on the knowledge
      produced on the topics: the impact of the mental illness in the family, the
      impact of the family environment in the evolution of the eating and the
      experience family with the mental illness. The measures of overload and express
      emotion are useful to guide public politics and the practice professional,
      however in they do not give a multidimensional picture to them of the experience
      of the care. Research on the familiar experience contribute to the understanding
      of the present suffering in this experience and of the forms of confrontation
      adopted by the families, also contributing to perceive the differences of the
      cultural contexts in the confrontation of the families.

PMID- 22378528
TI  - [Transdisciplinarity in distance education: a new paradigm in Nursing education].
AB  - This article aimed to reflect on the need of applying transdisciplinarity in
      distance education, since it presumes a new model, transition, change, and
      transformation. The goal of distance education is the supportive use in virtual
      and interactive learning environments, allowing the integration of multiple media
      tools, in an organized manner, to the production, interaction and knowledge
      socialization elaboration. In Brazil, nursing education has several experiences
      in using distance education with promising results, demonstrating good acceptance
      on the part of students and improvements on teaching-learning process.

PMID- 22378529
TI  - [Puppet theatre as teaching strategy: a report of the experience].
AB  - The Didactics Applied to Care discipline is developed in the fifth semester of
      the nursing graduation course. It develops several theoretical-practical
      contents, among them, the teaching strategy. Our objective is to report the
      experience with the use of puppet theater to promote the oral health of children
      in a day nursery in the Sao Paulo East Zone. With this report we make it clear
      that the theoretical contents developed by the Didactics Applied to Care
      Discipline are essential to the practice of Health Education. The discipline
      allows us to develop multiple activities in the role of educator and in health
      promotion.

PMID- 22378530
TI  - [Occupational exposure to biological material: post-accident monitoring].

PMID- 22378531
TI  - Rights and duties before the exposure to biological hazards.

PMID- 22378532
TI  - Synthesis of small molecules targeting multiple DNA structures using click
      chemistry.
AB  - The ability of small molecules to target DNA forms the basis of many clinically
      used antitumour agents. This study examines the effects of novel 9-aminoacridine
      carboxamides, synthesised by click chemistry based upon the reactions of either 9
      (2-azidoethyl)amino or 9-propargylaminoacridine compounds, on various types of
      DNA tertiary structures. This gave either monomeric or dimeric compounds, the
      dimeric derivatives being the first unsymmetrical acridine dimers to be
      described. The compounds were assayed for duplex DNA, quadruplex DNA and four-way
      junction DNA binding. Their antiproliferative activity in the Human promyelocytic
      leukaemia cell line, HL60, was also assessed. Although for some of the compounds,
      notably the acridine 4-carboxamides, activity correlated with DNA binding
      affinity, for others it did not, with the rigidly linked dimers in particular
      showing a complicated relationship between 3- and 4-carboxamide structure and
      biological activity. The monomeric 3-carboxamides were more effective at
      stabilising G-quadruplex structures and also gave more hits in the four-way
      junction stabilisation assay. There is clear evidence from the binding of the 3
      carboxamides that these compounds destabilise the open X form of the junction at
      lower concentrations and stabilise the X-stacked at higher concentrations. This
      might have implications for the biological activity of these compounds against
      proteins that bind to the Holliday junction (HJ).

PMID- 22378533
TI  - Who's who? Allocation of carbonyl reductase isoenzymes from Candida parapsilosis
      by combining bio- and computational chemistry.

PMID- 22378534
TI  - Resource quality affects carbon cycling in deep-sea sediments.
AB  - Deep-sea sediments cover ~70% of Earth's surface and represent the largest
      interface between the biological and geological cycles of carbon. Diatoms and
      zooplankton faecal pellets naturally transport organic material from the upper
      ocean down to the deep seabed, but how these qualitatively different substrates
      affect the fate of carbon in this permanently cold environment remains unknown.
      We added equal quantities of (13)C-labelled diatoms and faecal pellets to a cold
      water (-0.7  degrees C) sediment community retrieved from 1080 m in the Faroe
      Shetland Channel, Northeast Atlantic, and quantified carbon mineralization and
      uptake by the resident bacteria and macrofauna over a 6-day period. High-quality,
      diatom-derived carbon was mineralized >300% faster than that from low-quality
      faecal pellets, demonstrating that qualitative differences in organic matter
      drive major changes in the residence time of carbon at the deep seabed. Benthic
      bacteria dominated biological carbon processing in our experiments, yet showed no
      evidence of resource quality-limited growth; they displayed lower growth
      efficiencies when respiring diatoms. These effects were consistent in contrasting
      months. We contend that respiration and growth in the resident sediment microbial
      communities were substrate and temperature limited, respectively. Our study has
      important implications for how future changes in the biochemical makeup of
      exported organic matter will affect the balance between mineralization and
      sequestration of organic carbon in the largest ecosystem on Earth.

PMID- 22378535
TI  - Metagenomic and metaproteomic insights into bacterial communities in leaf-cutter
      ant fungus gardens.
AB  - Herbivores gain access to nutrients stored in plant biomass largely by harnessing
      the metabolic activities of microbes. Leaf-cutter ants of the genus Atta are a
      hallmark example; these dominant neotropical herbivores cultivate symbiotic
      fungus gardens on large quantities of fresh plant forage. As the external
      digestive system of the ants, fungus gardens facilitate the production and
      sustenance of millions of workers. Using metagenomic and metaproteomic
      techniques, we characterize the bacterial diversity and physiological potential
      of fungus gardens from two species of Atta. Our analysis of over 1.2 Gbp of
      community metagenomic sequence and three 16S pyrotag libraries reveals that in
      addition to harboring the dominant fungal crop, these ecosystems contain abundant
      populations of Enterobacteriaceae, including the genera Enterobacter, Pantoea,
      Klebsiella, Citrobacter and Escherichia. We show that these bacterial communities
      possess genes associated with lignocellulose degradation and diverse biosynthetic
      pathways, suggesting that they play a role in nutrient cycling by converting the
      nitrogen-poor forage of the ants into B-vitamins, amino acids and other cellular
      components. Our metaproteomic analysis confirms that bacterial glycosyl
      hydrolases and proteins with putative biosynthetic functions are produced in both
      field-collected and laboratory-reared colonies. These results are consistent with
      the hypothesis that fungus gardens are specialized fungus-bacteria communities
      that convert plant material into energy for their ant hosts. Together with recent
      investigations into the microbial symbionts of vertebrates, our work underscores
      the importance of microbial communities in the ecology and evolution of
      herbivorous metazoans.

PMID- 22378536
TI  - Microbial diversity in arctic freshwaters is structured by inoculation of
      microbes from soils.
AB  - Microbes are transported in hydrological networks through many environments, but
      the nature and dynamics of underlying microbial metacommunities and the impact of
      downslope inoculation on patterns of microbial diversity across landscapes are
      unknown. Pyrosequencing of small subunit ribosomal RNA gene hypervariable regions
      to characterize microbial communities along a hydrological continuum in arctic
      tundra showed a pattern of decreasing diversity downslope, with highest species
      richness in soil waters and headwater streams, and lowest richness in lake water.
      In a downstream lake, 58% and 43% of the bacterial and archaeal taxa,
      respectively, were also detected in diverse upslope communities, including most
      of the numerically dominant lake taxa. In contrast, only 18% of microbial
      eukaryotic taxa in the lake were detected upslope. We suggest that patterns of
      diversity in surface waters are structured by initial inoculation from microbial
      reservoirs in soils followed by a species-sorting process during downslope
      dispersal of both common and rare microbial taxa. Our results suggest that,
      unlike for metazoans, a substantial portion of bacterial and archaeal diversity
      in surface freshwaters may originate in complex soil environments.

PMID- 22378538
TI  - Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery.
AB  - In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more
      and more attention for their potential biomedical applications. With their
      tailored mesoporous structure and high surface area, MSNs as drug delivery
      systems (DDSs) show significant advantages over traditional drug nanocarriers. In
      this review, we overview the recent progress in the synthesis of MSNs for drug
      delivery applications. First, we provide an overview of synthesis strategies for
      fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in
      vivo biocompatibility and biotranslocation of MSNs are discussed in relation to
      their chemophysical properties including particle size, surface properties,
      shape, and structure. The review also highlights the significant achievements in
      drug delivery using mesoporous silica nanoparticles and their multifunctional
      counterparts as drug carriers. In particular, the biological barriers for nano
      based targeted cancer therapy and MSN-based targeting strategies are discussed.
      We conclude with our personal perspectives on the directions in which future work
      in this field might be focused.

PMID- 22378537
TI  - Metagenomic analysis of a stable trichloroethene-degrading microbial community.
AB  - Dehalococcoides bacteria are the only organisms known to completely reduce
      chlorinated ethenes to the harmless product ethene. However, Dehalococcoides
      dechlorinate these chemicals more effectively and grow more robustly in mixed
      microbial communities than in isolation. In this study, the phylogenetic
      composition and gene content of a functionally stable trichloroethene-degrading
      microbial community was examined using metagenomic sequencing and analysis. For
      phylogenetic classification, contiguous sequences (contigs) longer than 2500 bp
      were grouped into classes according to tetranucleotide frequencies and assigned
      to taxa based on rRNA genes and other phylogenetic marker genes. Classes were
      identified for Clostridiaceae, Dehalococcoides, Desulfovibrio, Methanobacterium,
      Methanospirillum, as well as a Spirochete, a Synergistete, and an unknown
      Deltaproteobacterium. Dehalococcoides contigs were also identified based on
      sequence similarity to previously sequenced genomes, allowing the identification
      of 170 kb on contigs shorter than 2500 bp. Examination of metagenome sequences
      affiliated with Dehalococcoides revealed 406 genes not found in previously
      sequenced Dehalococcoides genomes, including 9 cobalamin biosynthesis genes
      related to corrin ring synthesis. This is the first time that a Dehalococcoides
      strain has been found to possess genes for synthesizing this cofactor critical to
      reductive dechlorination. Besides Dehalococcoides, several other members of this
      community appear to have genes for complete or near-complete cobalamin
      biosynthesis pathways. In all, 17 genes for putative reductive dehalogenases were
      identified, including 11 novel ones, all associated with Dehalococcoides. Genes
      for hydrogenase components (271 in total) were widespread, highlighting the
      importance of hydrogen metabolism in this community. PhyloChip analysis confirmed
      the stability of this microbial community.

PMID- 22378539
TI  - Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3
      double-deficient mice caused by increased tissue inhibitor of metalloproteinases
      3 deposition and delayed aggrecan degradation.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) and matrilin 3 are
      extracellular matrix proteins that are abundant in cartilage. As adaptor
      molecules, both proteins bridge and stabilize macromolecular networks consisting
      of fibrillar collagens and proteoglycans. Mutations in the genes coding for COMP
      and matrilin 3 have been linked to human chondrodysplasias, while in mice,
      deficiency in COMP or matrilin 3 does not cause any pronounced skeletal
      abnormalities. Given the similar functions of COMP and matrilin 3 in the assembly
      and stabilization of the extracellular matrix, our aim was to determine whether
      these proteins could functionally compensate for each other. METHODS: To assess
      this putative redundancy of COMP and matrilin 3, we generated COMP/matrilin 3
      double-deficient mice and performed an in-depth analysis of their skeletal
      development. RESULTS: At the newborn stage, the overall skeletal morphology of
      the double mutants was normal, but at 1 month of age, the long bones were
      shortened and the total body length reduced. Peripheral quantitative computed
      tomography revealed increased metaphyseal trabecular bone mineral density in the
      femora. Moreover, the degradation of aggrecan in the cartilage remnants in the
      metaphyseal trabecular bone was delayed, paralleled by increased deposition of
      tissue inhibitor of metalloproteinases 3 (TIMP-3). The structure and morphology
      of the growth plate were grossly normal, but in the center, focal closures were
      observed, a phenotype very similar to that described in matrix metalloproteinase
      13 (MMP-13)-deficient mice. CONCLUSION: We propose that a lack of COMP and
      matrilin 3 leads to increased deposition of TIMP-3, which causes partial
      inactivation of MMPs, including MMP-13, a mechanism that would explain the
      similarities in phenotype between COMP/matrilin 3 double-deficient and MMP-13
      deficient mice.

PMID- 22378540
TI  - Impact of carbamylation and glycation of collagen type I on migration of HT1080
      human fibrosarcoma cells.
AB  - Collagen type I is an abundant component of the extracellular matrix and due to
      its longevity, constitutes a prominent target of non-enzymatic post-translational
      in vivo modifications such as carbamylation and glycation. These protein
      modifications involved in aging, renal diseases and diabetes, are linked to
      elevated cancer risk. In this in vitro study, we investigated the impact of
      carbamylated and glycated collagen type I on the migratory behavior of the highly
      invasive HT1080 human fibrosarcoma cells. The proliferation of HT1080 on modified
      collagens did not differ from that on native form. The glycated collagen delayed
      the cell adhesion time whereas the carbamylated one had no effect. The migration
      ability of HT1080 was studied by quantifying single cell speed using
      videomicroscopy. Glycation strongly inhibited mean cell speed by 47% whereas
      carbamylation moderately affected it by 12%. In addition, the influence of these
      collagen modifications on actin and vinculin organization was studied. On the
      glycated collagen, 63% of cells revealed a dramatic loss of actin stress fibers
      vs. 28% on the carbamylated one. In these cells, disorganized F-actin was
      accompanied with a disturbance of vinculin and both proteins were localized at
      the rim of the cells. Concerning the focal adhesion kinase (FAK) expression,
      glycated collagen only induced a significant inhibition. Whereas, both collagen
      modifications provoked a differential inhibition of FAK phosphorylation state by
      25% for carbamylation and 60% for glycation. In conclusion, our data suggest
      that, in vivo, collagen glycation and carbamylation may affect tumor cell
      metastasis. This suggestion is supported by clinical studies reporting less
      aggressive tumors in diabetic or uremic patients. Consequently, the impact of
      such post-translational modifications has to be taken into account in order to
      better understand the link between aging, diabetes or uremia and cancer
      progression.

PMID- 22378541
TI  - Small-caliber vascular prosthesis prototype based on controlled release of
      heparin from mesochannels and its enhanced biocompatibility.
AB  - A novel small-caliber vascular prosthesis prototype is proposed on the basis of a
      new heparin release system, that is, the controlled delivery of heparin from
      mesochannels. Fabrication of mesochannels on artificial biomaterials is
      successfully achieved through epitaxial growth of mesoporous silica nanoparticles
      on expanded polytetrafluoroethylene grafts, and thus heparin can be immobilized
      through a space limitation effect, thereby avoiding the loss of bioactivity and
      enabling long-lasting release. The adsorption and release of heparin are
      controlled by adjusting the adsorbate-adsorbent interaction through tailoring the
      mesostructure. Owing to the continuous and sustained release of heparin, the
      performances of artificial vessels are greatly improved, thus paving a new way to
      prepare functional blood-contacting biomaterials with high biocompatibility.

PMID- 22378542
TI  - Histopathology of de novo autoimmune hepatitis.
AB  - De novo autoimmune hepatitis (DAIH) is a well-recognized complication of
      pediatric liver transplantation (LT). The diagnosis is largely based on elevated
      liver function test results and the development of autoimmune antibodies. The
      histology of DAIH was first described in 1998. We present detailed histological
      data from the largest series to date of pretreatment and posttreatment biopsy
      samples from pediatric LT patients with DAIH. The histological evaluation
      included first an assessment of the predominant pattern of injury (hepatitis,
      rejection, or bile duct obstruction). Then, the necroinflammatory activity
      (interface, lobular, and perivenular), plasma cell density, rejection activity
      index, and fibrosis were scored. Seventy of 685 pediatric patients (10.2%) who
      underwent LT developed DAIH according to clinical and biopsy findings. Fifty-one
      pretreatment biopsy samples and 38 posttreatment biopsy samples were available
      for a retrospective review. The predominant pattern of injury (hepatitis,
      rejection, or bile duct obstruction) was determined, and biopsy samples were
      scored for the necroinflammatory activity (interface, lobular, and perivenular),
      plasma cell density, rejection activity index, and fibrosis. The most common
      pattern of injury was lobular hepatitis, which was frequently unaccompanied by
      interface necroinflammatory activity or prominent plasma cell infiltrates. Seven
      of the 51 cases had features strongly suggestive of acute rejection.
      Posttreatment biopsy samples showed a reduction in the degree of
      necroinflammatory activity and plasma cell infiltrates. In most patients, the
      degree of fibrosis was stable or had regressed. Because the histological features
      of DAIH are variable and nonspecific, a high index of suspicion and correlation
      with autoimmune antibodies are necessary to establish the diagnosis. In the
      majority of patients with DAIH, treatment appears to yield good clinical outcomes
      and histological improvements.

PMID- 22378543
TI  - Assessing cortical network properties using TMS-EEG.
AB  - The past decade has seen significant developments in the concurrent use of
      transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to
      directly assess cortical network properties such as excitability and connectivity
      in humans. New hardware solutions, improved EEG amplifier technology, and
      advanced data processing techniques have allowed substantial reduction of the TMS
      induced artifact, which had previously rendered concurrent TMS-EEG impossible.
      Various physiological artifacts resulting from TMS have also been identified, and
      methods are being developed to either minimize or remove these sources of
      artifact. With these developments, TMS-EEG has unlocked regions of the cortex to
      researchers that were previously inaccessible to TMS. By recording the TMS-evoked
      response directly from the cortex, TMS-EEG provides information on the
      excitability, effective connectivity, and oscillatory tuning of a given cortical
      area, removing the need to infer such measurements from indirect measures. In the
      following review, we investigate the different online and offline methods for
      reducing artifacts in TMS-EEG recordings and the physiological information
      contained within the TMS-evoked cortical response. We then address the use of TMS
      EEG to assess different cortical mechanisms such as cortical inhibition and
      neural plasticity, before briefly reviewing studies that have utilized TMS-EEG to
      explore cortical network properties at rest and during different functional brain
      states.

PMID- 22378545
TI  - Pd-catalyzed asymmetric synthesis of N-allenyl amides and their Au-catalyzed
      cycloisomerizative hydroalkylation: a new route toward enantioenriched
      pyrrolidones.

PMID- 22378544
TI  - A comparison of the effect of age on levator ani and obturator internus muscle
      cross-sectional areas and volumes in nulliparous women.
AB  - AIMS: Functional tests have demonstrated minimal loss of vaginal closure force
      with age. So we tested the null hypotheses that age neither affects the maximum
      cross-sectional area (CSA) nor the volume of the levator muscle. Corresponding
      hypotheses were also tested in the adjacent obturator internus muscle, which
      served as a control for the effect of age on appendicular muscle in these women.
      METHODS: Magnetic resonance images of 15 healthy younger (aged 21-25 years) and
      12 healthy older nulliparous women (aged >63 years) were selected to avoid the
      confounding effect of childbirth. Models were created from tracing outlines of
      the levator ani muscle in the coronal plane, and obturator internus in the axial
      plane using 3D Slicer v. 3.4. Muscle volumes were calculated using Slicer, while
      CSA was measured using ImagewareTM at nine locations. The hypotheses were tested
      using repeated measures analysis of variance with P < 0.05 being considered
      significant. RESULTS: The effect of age did not reach statistical significance
      for the decrease in levator ani muscle maximum CSA or the decrease in volume
      (4.3%, P = 0.62 and 10.9%, 0.12, respectively). However, age did significantly
      adversely decrease obturator internus muscle maximum CSA and volume (24.5% and
      28.2%, P < 0.001, respectively). Significant local age-related changes were
      observed dorsally in both muscles. CONCLUSIONS: Unlike the adjacent appendicular
      muscle, obturator internus, the levator ani muscle in healthy nullipara does not
      show evidence of significant age-related atrophy.

PMID- 22378546
TI  - Paroxysmal autonomic instability with dystonia in a child: rare manifestation of
      an interpeduncular tuberculoma.
AB  - The term 'paroxysmal autonomic instability with dystonia' was first given for a
      group of symptoms comprising diaphoresis, intermittent agitation, hypertension,
      hyperthermia, tachycardia, tachypnea, and extensor posturing. This usually occurs
      as a complication of severe brain injury and is infrequently reported in cases of
      cerebral infection. We report a 1-year-old child with intracranial tuberculoma
      with symptoms of paroxysmal autonomic instability with dystonia. Pertinent
      literature is reviewed emphasizing pathophysiology and available treatment
      options.

PMID- 22378547
TI  - Determination of folic acid in milk, milk powder and energy drink by an indirect
      immunoassay.
AB  - BACKGROUND: Folic acid (FA) is essential for healthy people (reference daily
      intake 400 ug day-1) and pregnant women (600 ug day-1). Insufficient intake of FA
      will increase the risk of neural tube defects in newborns. In this study an
      indirect enzyme-linked immunosorbent assay was developed for rapid and convenient
      detection of FA in vitamin-fortified foods. RESULTS: A carbodiimide-modified
      active ester method was used to synthesise the immunogen (FA-bovine serum albumin
      (BSA) conjugate) to raise polyclonal antibodies for FA. The coupling ratio of FA
      with BSA was determined to be 14:1 (molar ratio). The detection limit of the
      immunoassay was 3.0 ng mL-1 in buffer, 3.52 ng mL-1 in energy drink, 11.91 ng mL
      1 in milk and 16.50 ng mL-1 in milk powder. Intra- and inter-assay variability
      ranged from 6.6 to 15.1%. Analytical recoveries of FA-spiked samples were 88.3
      108.9%. CONCLUSION: The immunoassay developed in this study can be used as a
      simple, rapid and accurate method for fast semi-quantitative and quantitative on
      site analysis of FA in food products.

PMID- 22378548
TI  - The SARS-like coronaviruses: the role of bats and evolutionary relationships with
      SARS coronavirus.
AB  - Bats represent an order of great evolutionary success, with elevated geographical
      diffusion and species diversity. This order harbors viruses of high variability
      which have a great possibility of acquiring the capacity of infecting other
      animals,including humans. Bats are the natural reservoir for several viruses
      genetically closely related to the SARScoronavirus which is the etiological agent
      of severe acute respiratory syndrome (SARS), a human epidemic which emerged in
      China in 2002-2003. In the last few years, it has been discovered that the
      association between coronaviruses and bats is a worldwide phenomenon, and it has
      been hypothesised that all mammalian coronaviruses were derived from ancestral
      viruses residing in bats. This review analyzes the role of bats as a reservoir of
      zoonotic viruses focusing more extensively on SARS-related coronaviruses and
      taking into account the role of African and European strains in the evolutionary
      history of these viruses.

PMID- 22378550
TI  - GIV noroviruses and other enteric viruses in bivalves: a preliminary study.
AB  - We evaluated the presence of the enteric viruses: norovirus, adenovirus,
      enterovirus, astrovirus, hepatitis A virus, and hepatitis E virus in bivalves
      using nested PCR methods and cell culture assays. Noroviruses GII.4 and GIV.1,
      adenoviruses types 1 and 2, hepatitis A, and echovirus type 7 were detected in
      the shellfish tested, which were often co-infected. This is the first study to
      detect such a high level of viral contamination in Italian mussels (up to four
      different viral groups in a single sample), and the first to document the
      presence of GIV NoV in shellfish.

PMID- 22378551
TI  - Genetic engineering of Lactococcus lactis to produce an amylase inhibitor for
      development of an anti-diabetes biodrug.
AB  - Diabetes is known as a multifactorial disease. The treatment of diabetes is
      complicated due to its inherent pathophysiological factors related to the
      disease. One of the complications of diabetes is postprandial hyperglycemia.
      Glucosidase inhibitors, particularly ?-amylase inhibitors can help manage
      postprandial hyperglycemia. The low molecular weight inhibitor of ? -amylases
      called PAMI (peptide amylase inhibitor) inhibits the ? -amylase. In this study we
      cloned this amylase blocker PAMI in Lactococcus lactis. Using this Lactococcus
      lactis expressing the PAMI, we prepared yogurt and fed it to diabetic mice
      models. There was decrease in the blood glucose level after 20 days of oral
      administration of the yogurt. This product be used as a biodrug in maintaining
      the blood glucose level in diabetic patients.

PMID- 22378552
TI  - Characterization of wetland quorum quenching Pseudomonas aeruginosa strain 2SW8
      and its 2-heptyl-3-hydroxy-4-quinolone production.
AB  - Most Proteobacteria produce N-acylhomoserine lactones for bacterial cell-to-cell
      communication, a process called quorum sensing. Interference of quorum sensing,
      commonly known as quorum quenching, represents an important way to control quorum
      sensing. This work reports the isolation of quorum quenching bacterium strain
      2WS8 from Malaysia tropical wetland water (2 degrees 11'8"N, 102 degrees 15'2"E,
      in 2007) by using a modified version of a previously reported KG medium. Strain
      2WS8 was isolated based on its ability to utilize N-(3-oxohexanoyl)-L-homoserine
      lactone (3-oxo-C6-HSL) as the sole source of energy. This bacterium clustered
      closely to Pseudomonas aeruginosa PAO1. Strain 2SW8 possesses both quiP and pvdQ
      homologue acylase genes. Rapid Resolution Liquid Chromatography analysis
      confirmed that strain 2SW8 preferentially degraded N-acylhomoserine lactones with
      3-oxo group substitution but not those with unsubstituted groups at C3 position
      in the acyl side chain. Strain 2SW8 also showed 2-heptyl-3-hydroxy-4-quinolone
      production.

PMID- 22378549
TI  - Performance of genotypic tropism testing on proviral DNA in clinical practice:
      results from the DIVA study group.
AB  - OBJECTIVE: The DIVA study is aimed at setting up a standardized genotypic tropism
      testing on proviral-DNA for the routine clinical diagnostic-laboratory. METHODS:
      Twelve local centres and 5 reference centres (previously cross-validated) were
      identified. For inter-center validation-procedure, 60 peripheral-blood
      mononuclear cells (PBMCs) aliquots from 45 HAART-treated patients were randomly
      chosen for population V3 sequencing on proviral-DNA at local HIV centre and at
      reference-laboratory. Viral tropism was predicted by Geno2Pheno algorithm (False
      Positive Rate [FPR] = 20%) as proposed by the European-Guidelines. Quantification
      of total HIV-1 DNA was based on a method described by Viard (2004). RESULTS:
      Quantification of HIV-1 DNA was available for 35/45 (77.8%) samples, and gave a
      median value of 598 (IQR:252- 1,203) copies/10 PBMCs. A total of 56/60 (93.3%)
      samples were successfully amplified by both the reference and the local
      virological centers. The overall concordance of tropism prediction between local
      and reference centers was 54/56 (96.4%). Results of tropism prediction by local
      centers were: 33/54 (61.1%) R5 and 21/54 (38.9%) X4/DM. CONCLUSION: There was
      high concordance in the genotypic tropism prediction based on proviral DNA among
      different virological centers throughout Italy. Our results are in line with
      other European studies, and support the use of genotypic tropism testing on
      proviral DNA in patients with suppressed plasma HIV-1 RNA candidate to CCR5
      antagonist treatment.

PMID- 22378553
TI  - Salmonella typhimurium infections in BALB/c mice: a comparison of tissue
      bioluminescence, tissue cultures and mice clinical scores.
AB  - In response to systemic infection, mice usually present specific behaviors such
      as reduced activity and feeding, ruffled fur, hunched position, ataxia and
      tremor. We aimed to compare tissue bioluminescence, tissue cultures and clinical
      scores of BALB/c mice as potentially complementary outcome measures of Salmonella
      disease progression In Balb/c mice. The clinical status of the mice was assessed
      by visual examination for motility, ruffled fur, hunched position, feeding,
      ataxia and tremor. Patterns of bioluminescent light emission indicated the
      progression of infection from the abdominal region (initial site) to secondary
      tissue sites, which was indicative of systemic infection. As the severity and
      progression of infection increased, the bioluminescence signal became both more
      prominent and more anatomically disseminated. Bioluminescent Imaging (BLI) of
      Salmonella that have been genetically engineered to be bioluminescent is a new
      method that gives the opportunity to track Salmonella dissemination in mice. BLI
      is a helpful method to estimate tissue Salmonella concentration and may reduce
      the number of mice used in experiments, providing the opportunity to obtain
      serial assessments of disease progression in a single mouse subject. Clinical
      scores helped us to assess the clinical status of BALB/c mice in systemic
      Salmonella infections.

PMID- 22378554
TI  - Genetic diversity of Iranian clinical isolates of Mycobacterium tuberculosis.
AB  - In the current study we aimed to execute a rather less complicated molecular
      tying method, i.e. the random amplification of polymorphic DNA (RAPD) analysis to
      find the heterogeneity of Iranian strains of Mycobacterium tuberculosis. The
      isolates comprised a total of 96 strains of M. tuberculosis collected from
      clinical specimens of patients in Isfahan and Tehran. The isolates were assigned
      to the species M. tuberculosis by the key conventional and molecular methods.
      They were then subjected to RAPD analysis by four arbitrary primers, namely, the
      primers 27F, 1525R, MS- GF and INS-2. They were then evaluated for the number and
      intensity of the band patterns. The RAPD profiles of the Iranian isolates showed
      a degree of heterogeneity which varied based on the primer used. However,
      analysis of the isolates by primer INS-2 revealed the highest degree of diversity
      yielding 31 distinguishable RAPD types. RAPD analysis provides a rapid and easy
      means of identifying heterogeneity among the M. tuberculosis isolates. This
      typing system might be considered a valuable alternative molecular typing for
      countries with limited resources provided that the reproducibility and
      reliability of the method is carefully assured.

PMID- 22378555
TI  - In vitro CMV-infection model in fresh and glycerolized skin graft.
AB  - Viral infections, especially cytomegalovirus (CMV), are a cause of death in
      burned patients. Aim of this study was to perform an in vitro CMV-infection model
      comparing fresh and glycerol-treated fibroblasts and keratinocytes. Cells were
      plated in plates for the two conditions. Each plate was set up with CMV
      dilutions. Immunofluorescence and real time PCR assays were performed. The assays
      were negative in both fresh and glycerolized keratinocytes. For fibroblasts, CMV
      DNA was positive in both conditions and immunofluorescence test only in fresh
      cells. Glycerol at 85% confirms its strong virucidal effect as reported also for
      other viruses.

PMID- 22378556
TI  - Evaluation of antimicrobial susceptibilities of rapidly growing mycobacteria by
      Sensititre RAPMYCO panel.
AB  - This study used Sensititre RAPMYCO to test the activities of amikacin, cefoxitin,
      ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, sulfamehoxazole,
      tigecycline and tobramycin against 25 clinical isolates of rapidly growing
      mycobacteria (RGM), including the common disease producing species Mycobacterium
      abscessus, Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium
      peregrinum. Analysis of the four different RGM species showed that isolates of M.
      fortuitum and M. peregrinum were more susceptible than M. abscessus and M.
      chelonae. Different antimicrobials showed a variable sensitivity in all strains.
      Therefore, each species and strain must be individually evaluated, and it is
      always advisable to perform in vitro sensitivity tests before the treatment of
      infections due to RGM.

PMID- 22378557
TI  - Early diagnosis of invasive pulmonary aspergillosis in a young immunocompetent
      patient.
AB  - A 22-year-old insulin-dependent diabetic male was admitted for diabetic
      ketoacidosis. He developed hospital-acquired pneumonia (HAP) for which empirical
      antibiotic and antifungal therapy was started on the ward. On day 6, clinical and
      laboratory findings worsened, and bronchoalveolar lavage (BAL) was performed.
      Serum real time-polymerase chain reaction (RT-PCR) indicated invasive pulmonary
      aspergillosis (IPA) and led to antifungal therapy being initiated 48 hours before
      the results of the BAL culture were available. Despite early appropriate
      antifungal therapy, however, the patient died on day 22 while being supported by
      venovenous extracorporeal membrane oxygenation.

PMID- 22378558
TI  - Trichomonads in pleural effusion: case report, literature review and utility of
      PCR for species identification.
AB  - Trichomonas tenax is a flagellated protozoan commonly found in the human oral
      cavity but of unusual occurrence in pulmonary infections. We describe a case of a
      67-year-old patient with glioblastoma who presented with severe pleurisy in the
      post-operative period while she was receiving high-dose corticotherapy. Several
      motile flagellated protozoa were identified in the pleural fluid. Trichomonas
      tenax was identified by molecular methods. Pulmonary infections with Trichomonads
      might be underestimated because of diagnostic difficulties. The utility of
      molecular biology for species identification is underlined and the pathogenicity
      of Trichomonad parasites in human lungs is discussed in light of previously
      reported cases.

PMID- 22378559
TI  - A rare case of sepsis due to Corynebacterium macginleyi from central venous
      catheter in an elderly woman.
AB  - Corynebacterium macginleyi is a gram positive rod that causes especially ocular
      infections: since now only six elderly cases of extraocular infection are
      described. A 76 years old bedridden woman with a central venous catheter was
      hospitalized for 10 days of persistent fever. She was treated before with
      vancomicin and then with imipenem. The clinical conditions improved and the
      patient was discharged after two weeks of hospitalization. Among recognised risk
      factors for this infection the advanced age, indwelling devices and
      immunosuppression seem the most important. On the other hand, the antibiotics of
      choice are glycopeptides while the association of another antibiotic is
      recommended in our opinion only in severe clinical manifestation.

PMID- 22378560
TI  - Acute liver failure: a rare clinical presentation of visceral leishmaniasis.
AB  - We recently re-examined a case of Visceral Leishmaniasis, in a 36-year-old
      caucasian immune-competent men with an unusual clinical presentation. Together
      with symptoms and signs of a severe acute liver involvement, he presented weight
      loss, huge spleen enlargement, pancytopenia and increased ?-globulin serum level
      with a high polyclonal peak. He had no fever, but over-abundant night sweats were
      frequent. The patient was considered to have liver cirrhosis, and the diagnosis
      of visceral leishmaniosis was made with a year's delay. From this case report we
      may learn that, despite an unusual clinical presentation, the diagnosis of
      visceral leishmaniasis should not be excluded when other characteristic signs and
      symptoms and laboratory abnormalities are present.

PMID- 22378561
TI  - Presence of HBV S-gene mutants in immunocompromised patients.

PMID- 22378562
TI  - A new case of meningitis due to Toscana virus.

PMID- 22378563
TI  - Cross-coupling of aryllithiums with aryl and vinyl halides in flow microreactors.
AB  - The use of Pd catalysts that contained a carbene ligand, such as PEPPSI-SIPr,
      speeded up the Murahashi coupling of ArLi with ArBr, by enabling its integration
      with the Br/Li exchange of ArBr with BuLi in flow. Space integration realized the
      rapid cross-coupling of two different ArBr substrates. However, the cross
      coupling reaction with vinyl halides could not be achieved under similar
      conditions. Pd(OAc)(2) was an effective catalyst, and the space integration of
      the Br/Li exchange of ArBr with BuLi and the Murahashi coupling with vinyl
      halides was successfully achieved.

PMID- 22378564
TI  - Multimodal imaging guided photothermal therapy using functionalized graphene
      nanosheets anchored with magnetic nanoparticles.
AB  - In this work, a nanoscale reduced graphene oxide-iron oxide nanoparticle (RGO
      IONP) complex is noncovalently functionalized with polyethylene glycol (PEG),
      obtaining a RGO-IONP-PEG nanocomposite with excellent physiological stability,
      strong NIR optical absorbance, and superparamagnetic properties. Using this
      theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and
      magnetic resonance imaging are carried out, uncovering high passive tumor
      targeting, which is further used for effective photothermal ablation of tumors in
      mice.

PMID- 22378565
TI  - An unprecedented 1,2-shift in the biosynthesis of the 3-aminosalicylate moiety of
      antimycins.

PMID- 22378566
TI  - Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and
      safety results from a phase III, randomized, placebo-controlled trial.
AB  - OBJECTIVE: Golimumab, administered subcutaneously every 4 weeks, has been shown
      to be effective in reducing the signs and symptoms of active psoriatic arthritis
      (PsA) through week 24 of the GO-REVEAL study. Herein we report 1-year clinical,
      radiographic, and safety findings. METHODS: Adult patients with active PsA (>=3
      swollen and >=3 tender joints) were randomly assigned to receive subcutaneous
      placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks through week 20. At
      week 16, patients with <10% improvement from baseline in swollen and tender joint
      counts entered a blinded early escape phase, with placebo crossover to golimumab
      50 mg, golimumab 50 mg increased to 100 mg, and golimumab 100 mg continued at 100
      mg. Patients receiving placebo who did not enter the early escape phase crossed
      over to golimumab 50 mg at week 24. Findings through 1 year are reported,
      including the second of 2 coprimary end points (i.e., change from baseline to
      week 24 in PsA-modified Sharp/van der Heijde score [SHS]). RESULTS: A total of
      405 patients were randomized: 113 to placebo and 146 each to the golimumab 50 mg
      and 100 mg groups. Mean changes in PsA-modified SHS from baseline to week 24 for
      the combined golimumab 50 mg and 100 mg group (-0.09) and the golimumab 50 mg
      group (-0.16) were significantly different versus placebo (0.27) (P = 0.015 and P
      = 0.011, respectively). Radiographic benefit was maintained through week 52 with
      golimumab. Clinical efficacy, including improvement in joint and skin responses
      and physical function, was maintained through 1 year. The frequency/types of
      adverse events were similar to those reported through week 24. CONCLUSION:
      Treatment of PsA with golimumab inhibited structural damage progression and
      demonstrated continued clinical efficacy and safety through 1 year.

PMID- 22378567
TI  - Comparing intracellular stability and targeting of sulfobetaine quantum dots with
      other surface chemistries in live cells.
AB  - The in vivo labeling of intracellular components with quantum dots (QDs) is very
      limited because of QD aggregation in the cell cytoplasm and/or QD confinement
      into lysosomal compartments. In order to improve intracellular targeting with
      QDs, various surface chemistries and delivery methods have been explored, but
      they have not yet been compared systematically with respect to the QD
      intracellular stability. In this work, the intracellular aggregation kinetics of
      QDs for three different surface chemistries based on ligand exchange or
      encapsulation with amphiphilic polymers are compared. For each surface chemistry,
      three delivery methods for bringing the nanoparticles into the cells are
      compared: electroporation, microinjection, and pinocytosis. It is concluded that
      the QD intracellular aggregation behavior is strongly dependent on the surface
      chemistry. QDs coated with dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands
      diffuse freely in cells for longer periods of time than for QDs in the other
      chemistries tested, and they can access all cytoplasmic compartments. Even when
      conjugated to streptavidin, these DHLA-SB QDs remain freely diffusing inside the
      cytoplasm and unaggregated, and they are able to reach a biotinylated target
      inside HeLa cells. Such labeling was more efficient when compared to commercial
      streptavidin-conjugated QDs, which may be due to the smaller size of DHLA-SB QDs
      and/or to their superior intracellular stability.

PMID- 22378568
TI  - Neuroprotective effects of ginseng pectin through the activation of ERK/MAPK and
      Akt survival signaling pathways.
AB  - In this study, we investigated the neuroprotective activities of ginseng pectin
      (GP) against hydrogen peroxide (H2O2)-induced neuronal toxicity in different
      neuronal cells. GP selectively attenuated H2O2-induced damage up to 26% in
      primary cortical neuron cells and human glioblastoma U87 cells. Following H2O2
      exposure, DAPI staining and neuron-specific beta-tubulin antibody probing
      indicated that GP maintained cell integrity and decreased nuclei condensation.
      Data from western blot analysis revealed that pre-treatment with GP increased the
      phosphorylation of both the extracellular signal-regulated kinases 1 and 2
      (ERK1/2) and Akt in cortical neuron cells. However, the phosphorylation of ERK1/2
      was increased, but that of Akt was decreased in U87 cells. These results suggest
      that the protective effects of GP against H2O2-induced apoptosis may be due to
      the activation of the phosphorylation of ERK1/2 and Akt; however, the mechanisms
      involved differ depending on the cell line. This neuroprotective property
      indicates that GP could serve as a potential therapeutic agent for
      neurodegenerative diseases.

PMID- 22378570
TI  - Commentary.

PMID- 22378569
TI  - A patient with prolonged paralysis.

PMID- 22378571
TI  - Commentary.

PMID- 22378572
TI  - A message from the laboratory community to the National Cholesterol Education
      Program Adult Treatment Panel IV.

PMID- 22378573
TI  - Low hemoglobin A(1c)--good diabetic control?

PMID- 22378577
TI  - Is laparoscopic surgery an option to support prophylactic colectomy in adolescent
      patients with Familial Adenomatous Polyposis (FAP)?
AB  - BACKGROUND: Prophylactic surgery is still considered the standard treatment for
      patients with Familial Adenomatous Polyposis (FAP). Laparoscopic (Lap) surgery
      has been introduced as an alternative approach. The aim was to evaluate the
      feasibility and short- to long-term outcomes after prophylactic FAP surgery in
      adolescent. PROCEDURES: A retrospective review of a database of adolescent
      patients with FAP identified through the Hereditary Colorectal Tumor Registry in
      a single Institution between 2005 and 2011. Patients underwent Lap total
      colectomy (TC) with ileo-rectal anastomosis (IRA) or proctocolectomy (PC) with
      ileal-pouch anal anastomosis (IPAA). The main outcomes were: Hospital stay,
      postoperative complications, desmoid tumor rates, tumor recurrence, long-term
      complications. RESULTS: Sixteen consecutive patients with median age 16 (range 13
      19) and median BMI 22 (17-29) underwent surgery. [correction made here after
      initial online publication]. Of them 14 patients had LAP TC with IRA and 2 had PC
      with IPAA. Operative time (median, range) was TC/IRA 270 (210-330) minutes;
      PC/IPAA 370 (360-380) minutes. Length of extraction site was cm (median, range)
      6(5-8). Lymph Node harvest (median, range) 81 (32-139). Postoperative stay days
      (median, range) were 6 (4-24). Five patients (31.2%) showed dysplasia on the
      pathological report and 3 of them showed severe dysplasia. Median follow-up time
      (FU) was 39 months, range (10-82). The anastomotic leak rate for 30 days was 2
      (12.5%). Pouch failure was 0. Post-surgical desmoid tumors rate was 1 (6.2%) and
      there was no tumor recurrence. Anastomotic stricture, SBO and mortality were
      zero. CONCLUSIONS: Lap approach is feasible and shows acceptable postoperative
      outcomes. Lap surgery can be an appealing alternative for prophylactic surgery in
      adolescent FAP patients. Pediatr Blood Cancer 2012; 59: 1223-1228. (c) 2012 Wiley
      Periodicals, Inc.

PMID- 22378579
TI  - Seeing is not necessarily believing.

PMID- 22378580
TI  - Referred itch and meridians.

PMID- 22378581
TI  - Traditional Chinese medicine patterns and recommended acupuncture points in
      infertile and fertile women.
AB  - BACKGROUND: Acupuncture is rooted in traditional Chinese medicine (TCM) and
      emphasises individualised treatment according to TCM patterns. Eight TCM patterns
      are regarded as typical for female infertility. There are no empirical data
      comparing these patterns in fertile and infertile women. OBJECTIVE: To identify
      and compare the TCM patterns and recommended acupuncture points in infertile and
      fertile women. The hypothesis that infertile and fertile women should differ in
      occurrence of TCM patterns described as typical for infertility was examined.
      METHODS: A cross-sectional study examined the distribution of TCM patterns and
      acupuncture points among 24 infertile and 24 fertile women. TCM patterns and
      points proposed by two acupuncturists were analysed. The odds ratio was used as
      the effect measure. RESULTS: Three patterns were found in more than 92% of the
      women. Five patterns occurred more frequently among infertile (p<=0.03), and four
      among fertile (p<=0.02) women. Only three of the eight patterns assumed typical
      for infertile women were more common among infertile women. Two of the eight
      patterns were more common among fertile women. Acupuncture points KI3, LI3 and
      SP6 were chosen for almost all women, whereas CV4, CV3 and ST29 were chosen more
      often for infertile women (p<0.03), and SP3 more often for fertile women
      (p<0.001). CONCLUSION: The data indicate that the presence of some, and the
      absence of other, TCM patterns are associated with infertility. These results are
      not consistent with the assumed associations between eight specific patterns and
      infertility, as maintained by TCM textbooks.

PMID- 22378582
TI  - Do acupuncture meridians exist? Correlation with referred itch (mitempfindung)
      stimulus and referral points.
AB  - OBJECTIVE: To describe the relationship between referred itch (mitempfindung)
      stimulus and referral points and acupuncture meridians, noting that the
      neuroanatomical mechanism of mitempfindung has never previously been
      satisfactorily explained. METHODS: Analysis of clinical findings in the author as
      well as subjects in four previously described studies, comparing proportions in
      each of five groups. RESULTS: Ninety-two per cent (range 85-94%) of mitempfindung
      point pairs (stimulus and referral) aligned to a recognised acupuncture meridian
      with no statistical difference (p<0.05) between the five data sources.
      CONCLUSION: While previous authors have speculated on an association between
      mitempfindung and acupuncture, this is the first description of a relationship
      between stimulus and referral points and acupuncture meridians. The author
      suggests that the transmission of mitempfindung along acupuncture meridians may
      involve a series of C-fibre-Merkel cell relays, with the final referred itch
      sensation caused by substance P release triggering mast cell degranulation.

PMID- 22378583
TI  - The effect of electroacupuncture and tramadol on experimental tourniquet pain.
AB  - OBJECTIVES: The hypoalgesic effect of electroacupuncture (EA) was directly
      compared with the analgesic effect of pharmacological interventions using the
      submaximum effort tourniquet technique (SETT). METHODS: 125 healthy subjects
      (mean age 24.44+/-4.46 years; 62.4% female, 37.6% male) performed SETT at
      baseline and under one of five experimental conditions (n=25 per group): EA (2 Hz
      with burst pulses in alternating one-phase-square wave pulses; burst length 180
      MUs, burst frequency 80 Hz, stimulation time/pulse width 3 s), tramadol (50 mg),
      ibuprofen (400 mg), placebo pill or non-treatment control. EA was performed at
      LI4 and LI10 contralaterally with stimulation beginning 20 min before SETT and
      lasting throughout SETT. The pharmacological interventions were given in a double
      blind design 1 h before the SETT assessment. RESULTS: Subjects showed a
      hypoalgesic effect of the opiate and of the EA for subjective pain rating (EA
      p=0.0051; tramadol p=0.0299), and pain tolerance index (time/rating) (EA p=0.043;
      tramadol p=0.047) analysed using analysis of covariance. More subjects reached
      the strict time limit of 30 min (analysed by logistic regression and adjusted OR
      as a post-hoc analysis) under EA compared with most other experimental
      conditions. Only EA and tramadol were not significantly different (95% Wald
      confidence limits: non-treatment control vs EA 0.011 to 0.542; placebo pill vs EA
      0.009 to 0.438; ibuprofen vs EA 0.021 to 0.766; tramadol vs EA 0.065 to 1.436).
      CONCLUSION: In a laboratory setting, an EA procedure was as effective as a single
      dose of an orally administered opiate in reducing experimentally induced
      ischaemic pain.

PMID- 22378584
TI  - Electroacupuncture prevents ovariectomy-induced osteoporosis in rats: a
      randomised controlled trial.
AB  - BACKGROUND: Electroacupuncture (EA) treatment has been shown to increase bone
      mineral density (BMD) in ovariectomised (OVX) rats; however, the underlying
      mechanisms remain unclear. OBJECTIVE: To systematically evaluate the effects of
      EA on OVX rats and the Wnt/beta-catenin signalling pathway. METHODS: Three-month
      old female Sprague-Dawley rats were randomly divided into three different groups
      (n=10 each): sham operated control (sham operated), ovariectomy (OVX) and
      ovariectomy with EA treatment (OVX+EA). Rats in the OVX+EA group received 12-week
      EA treatments. RESULTS: Serum bone-specific alkaline phosphatase level (p<0.01),
      BMD of the proximal femoral metaphysis and the fifth lumbar (L5) vertebral body
      (both, p<0.05) and maximum load and energy to failure of L5 vertebral body (both
      p<0.01) were significantly higher in the OVX+EA group than in the OVX group.
      Trabecular area, trabecular width and trabecular number were significantly higher
      in the OVX+EA group by 66.9%, 29.2% and 30.3%, respectively, than in the OVX
      group (all, p<0.01). Trabecular separation was 31.9% lower in the OVX+EA group
      than in the OVX group (p<0.01). Quantitative real-time reverse transcription
      polymerised chain reaction indicated that the expressions of mRNAs for low
      density lipoprotein receptor-related protein 5 and beta-catenin were
      significantly increased in the OVX+EA group, as compared with the OVX group
      (p<0.01 and p<0.05, respectively). CONCLUSION: This study demonstrates that EA
      can prevent OVX-induced bone loss and deterioration of bone architecture and
      strength by stimulating the Wnt/beta-catenin signalling pathway. These findings
      suggest that EA may bet a promising adjunct method for inhibiting OVX-induced
      osteoporosis in clinical settings.

PMID- 22378587
TI  - Mannich reactions of alkynes: mechanistic insights and the role of sub
      stoichiometric amounts of alkynylcopper(I) compounds in the catalytic cycle.

PMID- 22378585
TI  - The influence of PC6 on cardiovascular disorders: a review of central neural
      mechanisms.
AB  - PC6 is a classic acupuncture point in traditional Chinese medicine. It is
      considered to be effective when treating cardiovascular disorders. In the present
      review the authors have focused on the neurophysiological bases of the effects of
      PC6 stimulation on cardiovascular mechanisms. Experimental studies have shown
      that the hypothalamic rostral ventrolateral medulla, arcuate nucleus and
      ventrolateral periaqueductal gray are involved in acupuncture attenuation of
      sympathoexcitatory cardiovascular reflex responses. This long-loop pathway also
      appears to contribute to the long-lasting, acupuncture-mediated attenuation of
      sympathetic premotor outflow and excitatory cardiovascular reflex responses.
      Acupuncture of PC6 modulates the activity in the cardiovascular system, an effect
      that may be attributed to attenuation of sympathoexcitatory cardiovascular reflex
      responses.

PMID- 22378588
TI  - Writing affects the brain network of reading in Chinese: a functional magnetic
      resonance imaging study.
AB  - We examined the hypothesis that learning to write Chinese characters influences
      the brain's reading network for characters. Students from a college Chinese class
      learned 30 characters in a character-writing condition and 30 characters in a
      pinyin-writing condition. After learning, functional magnetic resonance imaging
      collected during passive viewing showed different networks for reading Chinese
      characters and English words, suggesting accommodation to the demands of the new
      writing system through short-term learning. Beyond these expected differences, we
      found specific effects of character writing in greater activation (relative to
      pinyin writing) in bilateral superior parietal lobules and bilateral lingual gyri
      in both a lexical decision and an implicit writing task. These findings suggest
      that character writing establishes a higher quality representation of the visual
      spatial structure of the character and its orthography. We found a greater
      involvement of bilateral sensori-motor cortex (SMC) for character-writing trained
      characters than pinyin-writing trained characters in the lexical decision task,
      suggesting that learning by doing invokes greater interaction with sensori-motor
      information during character recognition. Furthermore, we found a correlation of
      recognition accuracy with activation in right superior parietal lobule, right
      lingual gyrus, and left SMC, suggesting that these areas support the facilitative
      effect character writing has on reading. Finally, consistent with previous
      behavioral studies, we found character-writing training facilitates connections
      with semantics by producing greater activation in bilateral middle temporal gyri,
      whereas pinyin-writing training facilitates connections with phonology by
      producing greater activation in right inferior frontal gyrus.

PMID- 22378589
TI  - Discrimination of organic coffee via Fourier transform infrared-photoacoustic
      spectroscopy.
AB  - BACKGROUND: Procedures for the evaluation of the origin and quality of ground and
      roasted coffee are constantly needed for the associated industry due to
      complexity of the related market. Conventional Fourier transform infrared (FTIR)
      spectroscopy can be used for detecting changes in functional groups of compounds,
      such as coffee. However, dispersion, reflection and non-homogeneity of the sample
      matrix can cause problems resulting in low spectral quality. On the other hand,
      sample preparation frequently takes place in a destructive way. To overcome these
      difficulties, in this work a photoacoustic cell has been adapted as a detector in
      a FTIR spectrophotometer to perform a study of roasted and ground coffee from
      three varieties of Coffea arabica grown by organic and conventional methods.
      RESULTS: Comparison between spectra of coffee recorded by FTIR-photoacoustic
      spectrometry (PAS) and by FTIR spectrophotometry showed a better resolution of
      the former method, which, aided by principal components analysis, allowed the
      identification of some absorption bands that allow the discrimination between
      organic and conventional coffee. CONCLUSION: The results obtained provide
      information about the spectral behavior of coffee powder which can be useful for
      establishing discrimination criteria. It has been demonstrated that FTIR-PAS can
      be a useful experimental tool for the characterization of coffee.

PMID- 22378590
TI  - Site-selective affinity labelling of maltose binding protein in bacterial cells.

PMID- 22378591
TI  - Home-based self-delivered mirror therapy for phantom pain: a pilot study.
AB  - OBJECTIVE: To test the feasibility and preliminary efficacy of self-delivered
      home-based mirror therapy for phantom pain. DESIGN: Uncontrolled prospective
      treatment outcome pilot study. PARTICIPANTS: Forty community-dwelling adults with
      unilateral amputation and phantom pain > 3 on a 0-10 numeric rating scale
      enrolled either during a one-time study visit (n = 30) or remotely (n = 10).
      METHODS: Participants received an explanation of mirror therapy and were asked to
      self-treat for 25 min daily. Participants completed and posted back sets of
      outcomes questionnaires at months 1 and 2 post-treatment. Main outcome was
      average phantom pain intensity at post-treatment. RESULTS: A significant
      reduction in average phantom pain intensity was found at month 1 (n = 31, p =
      0.0002) and at month 2 (n = 26, p = 0.002). The overall median percentage
      reduction at month 2 was 15.4%. Subjects with high education (> 16 years)
      compared with low education (< 16 years) (37.5% vs 4.1%) had greater reduction in
      pain intensity (p = 0.01). CONCLUSION: These findings support the feasibility and
      efficacy of home-based self-delivered mirror therapy; this low-cost treatment may
      defray medical costs, therapy visits, and the patient travel burden for people
      with motivation and a high level of education. More research is needed to
      determine methods of cost-effective support for people with lower levels of
      education.

PMID- 22378592
TI  - Photooxygenation of a microbial arene oxidation product and regioselective
      Kornblum-DeLaMare rearrangement: total synthesis of zeylenols and zeylenones.
AB  - We report the enantioselective total syntheses of zeylenol (+)-1, as well as its
      congeners (-)-7 and 16, and of 3-O-debenzoylzeylenone 28. To this end, a new
      variant of the Kornblum-DeLaMare rearrangement, which utilises neighbouring-group
      participation to impart regioselectivity, has been developed. The approach
      employs photooxygenation of building blocks derived from a microbial arene
      oxidation product.

PMID- 22378594
TI  - Target-selective photodegradation of HIV-1 protease and inhibition of HIV-1
      replication in living cells by designed fullerene-sugar hybrids.

PMID- 22378595
TI  - Amplified spontaneous emission of surface plasmon polaritons with unusual angle
      dependent response.
AB  - Loss issues are fundamentally crucial for the application of surface plasmon
      polaritons (SPPs). In this study the amplified spontaneous emission (ASE) of SPPs
      in a typical Kretschmann configuration is observed and shows an unusually
      broadened angular response with increased pump intensity. Theoretical models are
      further developed to verify the results and understand the amplification of SPPs
      in Fourier space.

PMID- 22378593
TI  - Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS
      2011.
AB  - Normal functioning of the urinary bladder and the distal gut is an essential part
      of daily physiological activity coordinated by the peripheral and central nervous
      systems. Pathological changes in one of these organs may induce the development
      of cross-organ sensitization in the pelvis and underlie clinical co-morbidity of
      genitourinary and GI dysfunctions. Experimental human and animal data suggest
      that the bladder and distal colon interact under both normal and pathological
      conditions, however, the directions of these interactions can change dramatically
      depending on the nature and duration of the applied stimuli. This review article
      aimed to summarize the clinical data on colon-bladder cross-reflexes in healthy
      individuals, as well as in patients with co-morbid disorders. It also discusses
      currently used animal models, experimental approaches, and suggested mechanisms
      of colon-bladder cross-talk. Additionally, it provides an overview of the
      potential pharmacological targets to develop treatment options for patients with
      co-morbid disorders. Presented work resulted from the discussion of colon/bladder
      interactions during "Think Tank 9" presentations at the International
      Consultation on Incontinence Research Society meeting held in Bristol, UK, 2011.

PMID- 22378596
TI  - Development and application of multiple-probe scanning probe microscopes.
AB  - In the research of advanced materials based on nanoscience and nanotechnology, it
      is often desirable to measure nanoscale local electrical conductivity at a
      designated position of a given sample. For this purpose, multiple-probe scanning
      probe microscopes (MP-SPMs), in which two, three or four scanning tunneling
      microscope (STM) or atomic force microscope (AFM) probes are operated
      independently, have been developed. Each probe in an MP-SPM is used not only for
      observing high-resolution STM or AFM images but also for forming an electrical
      contact enabling nanoscale local electrical conductivity measurement. The world's
      first double-probe STM (DP-STM) developed by the authors, which was subsequently
      modified to a triple-probe STM (TP-STM), has been used to measure the
      conductivities of one-dimensional metal nanowires and carbon nanotubes and also
      two-dimensional molecular films. A quadruple-probe STM (QP-STM) has also been
      developed and used to measure the conductivity of two-dimensional molecular films
      without the ambiguity of contact resistance between the probe and sample.
      Moreover, a quadruple-probe AFM (QP-AFM) with four conductive tuning-fork-type
      self-detection force sensing probes has been developed to measure the
      conductivity of a nanostructure on an insulating substrate. A general-purpose
      computer software to control four probes at the same time has also been developed
      and used in the operation of the QP-AFM. These developments and applications of
      MP-SPMs are reviewed in this paper.

PMID- 22378597
TI  - A proposed modification to the Best Pharmaceuticals for Children Act to benefit
      pediatric oncology.

PMID- 22378599
TI  - Endothelial cell activation and proliferation in ovarian tumors: two distinct
      steps as potential markers for antiangiogenic therapy response.
AB  - Ovarian cancer is the second leading cause of cancer-related death in women
      worldwide. Since most patients are diagnosed in advanced disease stages, the
      starting point, early steps and molecular mechanisms of ovarian cancer
      angiogenesis are still incompletely characterized. Most immunohistochemical
      studies for assessment of microvessel density (MVD) in ovarian tumors are based
      on CD31, CD34 and CD105 immunostaining of tumor blood vessels. Yet, the
      proliferative status of tumor blood vessel endothelial cells has not as yet been
      used in the assessment of tumor blood vessels. The present study investigated the
      Ki67 proliferative index of tumor blood vessel endothelial cells highlighted with
      the CD34 panendothelial marker and the CD105 endothelial marker in ovarian
      cancers by antigen co-localization with a doublestaining immunohistochemical
      method. Lack of co-localization of CD105 and Ki67 in all types of ovarian tumors
      together with the presence of CD34+/Ki67-positive endothelial cells suggest that
      endothelial cell activation and proliferation are distinct steps in ovarian
      tumors. Differences in the proliferation index were observed in endothelial cells
      from blood vessels of the tumor core and those of the tumor peripheral zones.
      Potential specific targeting of activated and proliferating tumor blood vessels
      may provide clues for improving antiangiogenic therapy efficiency.

PMID- 22378600
TI  - Polarization-dependent SERS at differently oriented single gold nanorods.
AB  - We investigated the influence of the orientation of individual gold nanorods on
      the polarization-dependent single-particle surface-enhanced Raman spectroscopy
      (SERS) of adenine. Higher-order laser beams (radial and azimuthal polarizations)
      have been used in combination with a parabolic mirror-assisted confocal optical
      microscope. Based on the photoluminescence (PL) patterns of the single gold
      nanorods and the simulated electric-field distribution in the focus, we
      distinguished between isolated gold rods and clusters as well as single nanorods
      with different orientations. We found that for single gold nanorods lying flat on
      the substrate, the longitudinal particle plasmon resonance (PPR) mode can be
      excited more efficiently with the in-plane field component in the focus of an
      azimuthally polarized laser beam, which enables the observation of stronger
      enhanced adenine Raman spectra from the single gold nanorods compared to the case
      of a radially polarized beam.

PMID- 22378598
TI  - [Consensus statement haemorrhoidal disease].
AB  - Haemorrhoidal disease belongs to the most common benign disorders in the lower
      gastrointestinal tract. Treatment options comprise conservative as well as
      surgical therapy still being applied arbitrarily in accordance with the surgeon's
      expertise. The aim of this consensus statement was therefore to assess a stage
      dependent approach for treatment of haemorrhoidal disease to derive evidence
      based recommendations for clinical routine. The most common methods are discussed
      with respect of haemorrhoidal disease in extraordinary conditions like pregnancy
      or inflammatory bowel disease and recurrent haemorrhoids. Tailored
      haemorrhoidectomy is preferable for individualized treatment with regard to the
      shortcomings of the traditional Goligher classification in solitary or circular
      haemorrhoidal prolapses.

PMID- 22378601
TI  - Functional characterization of TPO-expanded CD34+ cord blood cells identifies
      CD34- CD61- cells as platelet-producing cells early after transplantation in
      NOD/SCID mice and rCD34+ cells as CAFC colony-forming cells.
AB  - Transplantation of thrombopoietin (TPO)-expanded cord blood CD34(+) cells
      accelerates human platelet recovery in NOD/SCID mice. It is unknown which
      subpopulations of the TPO-expanded cells mediate accelerated platelet recovery
      and bone marrow (BM) engraftment. In this study, the contribution of these
      subpopulations to human platelet appearance in the blood and BM engraftment was
      studied in NOD/SCID mice. Following transplantation of CD34(-) /CD61(-)/lineage(
      ) cells (Lin(-)), human platelets were detected in the blood of recipient mice
      from day 4. Both time to platelet recovery and blood platelet counts at 6 weeks
      after transplantation showed Lin(-) dose dependence. The Lin(-) population was
      virtually negative for lineage marker expression and lacked CD42b expression but
      was heterogeneous with regard to CD36 and CD38 expression, reflecting a
      population in transit but not fully committed toward the megakaryocyte (MK)
      lineage. Although no definitive phenotype could be established of the cells
      generating prompt platelet production and cells generating platelets 6 weeks
      after transplantation, this relatively heterogeneous Lin(-) population is
      prerequisite to accelerate platelet recovery in vivo. The interval to platelet
      recovery after transplantation of the CD34(+) cells remaining after expansion
      (rCD34(+)) was similar to mice transplanted with nonexpanded CD34(+) cells,
      although the total platelet counts and the engraftment levels in the BM were
      lower. Cobblestone area-forming cell colony-forming cells resided mostly in the
      rCD34(+) population. The pro-MK CD61(+) cells did not contribute to human
      platelet recovery or engraftment in the BM. Our study shows that not all expanded
      cells appear critical for transplantation. These data support that functional
      characterization of the expanded cell populations is warranted to make future
      expansion protocols suitable for clinical application.

PMID- 22378603
TI  - Electromechanical-assisted gait training after stroke: a systematic review
      comparing end-effector and exoskeleton devices.
AB  - OBJECTIVES: Although electromechanical-assisted gait training after stroke seems
      to be effective, in the absence of a direct comparison between electromechanical
      devices it is not clear which device may be the most effective for recovery of
      walking. The aim of this study was therefore to compare the effects of different
      devices used in gait training after stroke. DATA SOURCES: We searched the
      Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, AMED,
      SPORTDiscus, PEDro, COMPENDEX and INSPEC. In addition, we hand-searched relevant
      conference proceedings, trials and research registers, checked reference lists
      and contacted authors to identify further trials. STUDY SELECTION: Randomized
      studies were included. Authors independently selected trials for inclusion,
      assessed trial quality and extracted the data. DATA EXTRACTION: Data were
      extracted with the help of a standardized data extraction form. DATA SYNTHESIS:
      Data were pooled for meta-analysis. The primary outcome was the proportion of
      patients walking independently. RESULTS: We included 18 trials involving 885
      patients. We  found significantly higher rates of independent walking in end
      effector compared with exoskeleton-based training (p = 0.03). Complication rates
      in both groups were comparable. CONCLUSION: The results suggest that the type of
      electromechanical-assisted device might influence the outcome of gait
      rehabilitation after stroke.

PMID- 22378602
TI  - Central B-cell tolerance: where selection begins.
AB  - The development of an adaptive immune system based on the random generation of
      antigen receptors requires a stringent selection process that sifts through
      receptor specificities to remove those reacting with self-antigens. In the B-cell
      lineage, this selection process is first applied to IgM(+) immature B cells. By
      using increasingly sophisticated mouse models, investigators have identified the
      central tolerance mechanisms that negatively select autoreactive immature B cells
      and prevent inclusion of their antigen receptors into the peripheral B-cell pool.
      Additional studies have uncovered mechanisms that promote the differentiation of
      nonautoreactive immature B cells and their positive selection into the peripheral
      B-cell population. These mechanisms of central selection are fundamental to the
      generation of a naive B-cell repertoire that is largely devoid of self-reactivity
      while capable of reacting with any foreign insult.

PMID- 22378604
TI  - Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behcet's
      disease.
AB  - OBJECTIVE: Independent replication of the findings from genome-wide association
      studies (GWAS) remains the gold standard for results validation. Our aim was to
      test the association of Behcet's disease (BD) with the interleukin-10 gene (IL10)
      and the IL-23 receptor-IL-12 receptor beta2 (IL23R-IL12RB2) locus, each of which
      has been previously identified as a risk factor for BD in 2 different GWAS.
      METHODS: Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and
      42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD
      controls. Population stratification was assessed using a panel of 86 ancestry
      informative markers. RESULTS: Subtle evidence of population stratification was
      found in our data set. In IL10, rs1518111 was nominally associated with BD before
      and after adjustment for population stratification (odds ratio [OR] for T allele
      1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53
      * 10(-2) ; adjusted P [P(adj) ] = 1.43 * 10(-2) ), and rs1554286 demonstrated a
      trend toward association (P(unadj) = 6.14 * 10(-2) ; P(adj) = 3.21 * 10(-2) ).
      Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni
      correction for multiple testing, the most significant of which were rs17375018
      (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 * 10(-6) ), rs7517847
      (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 * 10(-6) ), and rs924080
      (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 * 10(-5) ). SNPs rs10489629,
      rs1343151, and rs1495965 were also significantly associated with BD in all tests
      performed. Results of meta-analyses of our data combined with data from other
      populations further confirmed the role of rs1518111, rs17375018, rs7517847, and
      rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R
      IL12RB2 were detected. Results of imputation analysis highlighted the importance
      of IL23R regulatory regions in the susceptibility to BD. CONCLUSION: These
      findings independently confirm, extend, and refine the association of BD with
      IL10 and IL23R-IL12RB2. These associations warrant further validation and
      investigation in patients with BD, as they may have implications for the
      development of novel therapies (e.g., immunosuppressive therapy targeted at IL
      23p19).

PMID- 22378605
TI  - Predictors of care seeking in women with urinary incontinence.
AB  - AIMS: To determine predictors of health care utilization in women with urinary
      incontinence (UI) from the population to specialty care. METHODS: The General
      Longitudinal Overactive Bladder Evaluation-UI is a population-based study on the
      natural history of UI in women >=40 years of age. Prevalence of UI was estimated
      using the Bladder Health Survey (BHS). Survey data were linked with electronic
      health records (EHRs) to examine factors associated with a clinical UI diagnosis
      using logistic regression. Risk factors analyzed included: UI symptoms, subtypes,
      bother, severity, duration, and effect on quality of life, and demographic and
      other health characteristics. All statistical tests were two-sided with a P-value
      < 0.05 being significant. RESULTS: The overall prevalence of any UI based on
      responses to the BHS was 1,618/4,064 (40%). Of the 1,618 women with UI, there
      were only 398 (25%) women with EHR (clinical) diagnosis of UI. Women with UI
      versus those without UI were more likely to be have a BMI >25 kg/m(2) (70% vs.
      58%), more likely to be parous (91% vs. 87%) and college educated (54% vs. 46%),
      P < 0.001. After adjusting for confounders in the model, variables significantly
      associated with clinical UI diagnosis included: older age (OR = 1.96), higher
      parity (> 1 birth) (OR = 1.76), higher urgency UI (OR = 1.08), adaptive behavior
      (OR = 1.2), and UI bother scores (OR = 1.01), as well as more frequent outpatient
      visits (OR = 1.03), P < 0.05. CONCLUSIONS: UI is a highly prevalent condition
      with only a minority of women seeking care. Factors associated with health care
      utilization include older age, parity (1+), number of doctor visits, urgency UI
      subtype, UI bother, and impact on behavior.

PMID- 22378606
TI  - Resin-derived hierarchical porous carbon spheres with high catalytic performance
      in the oxidative dehydrogenation of ethylbenzene.
AB  - Pre-shaped hierarchical porous carbon (HPC) spheres have been synthesized through
      a facile anion exchanged route. An industrial polymeric anion-exchange resin with
      a hierarchical pore structure was used as the carbon precursor. Its high porosity
      was conserved using an aluminate/silicate precursor forming a hard support to
      prevent the structural collapse during the carbonization process. Physicochemical
      bulk and surface properties of the obtained HPC spheres were characterized by X
      ray diffraction, scanning and transmission electron microscopy, N(2) 
      physisorption, and X-ray photoemission spectroscopy. Results obtained indicate
      that HPC keeps the abundant hierarchical porosity including meso- and macropores
      as well as the high surface area of the resin precursor. The as-synthesized HPC
      spheres were tested as a catalyst for oxidative dehydrogenation of ethylbenzene
      to styrene. The oxygen-rich catalyst surface formed under reaction conditions
      shows a high catalytic performance and stability, making HPC to a potential
      catalyst for this type of reaction.

PMID- 22378608
TI  - A deliberation on nanobubbles at surfaces and in bulk.
AB  - Surface and bulk nanobubbles are two types of nanoscopic gaseous domain that have
      recently been discovered in interfacial physics. Both are expected to be unstable
      to dissolution because of the high internal pressure driving diffusion and the
      surface tension which squeezes the gas out, but there is a rapidly growing body
      of experimental evidence that demonstrates both bubble types to be stable.
      However, the two types of bubbles also differ in many respects: surface
      nanobubble stability is most probably assisted by the nearby wall, which can
      repel the water (in the case of hydrophobicity), accept physisorbed gas
      molecules, and reduce the surface area through which outfluxing can occur; bulk
      nanobubbles, on the other hand, must stabilise themselves. This is perhaps
      through ionic shielding, perhaps through diffusive shielding, or perhaps through
      both. Herein, the features of both bubble types are described individually, their
      common and disparate features are discussed, and emerging applications are
      examined.

PMID- 22378607
TI  - ROS-inducible DNA cross-linking agent as a new anticancer prodrug building block.

PMID- 22378609
TI  - Growth, characterization, and properties of nanographene.
AB  - A systematic study on nanographene grown directly on silicon dioxide substrates
      is reported. The growth is carried out in a remote plasma-enhanced chemical vapor
      deposition system at a low temperature of around 550  degrees C with methane gas
      as the carbon source. Atomic force microscopy is used to characterize the
      nanographene morphology, and Raman spectroscopy, X-ray photoelectron
      spectroscopy, and scanning tunneling microscopy are exploited to identify the in
      plane sp(2)  bonding structures of nanographene samples. Electrical transport
      properties are measured at various temperatures down to 4 K. Tunneling effects,
      minimal conductance at the charge-neutral point, sheet resistances, and Dirac
      point position at different channel lengths are investigated. In addition,
      nanographene film possesses high transmittance properties, as indicated by
      transmittance spectra. Nanographene devices are fabricated from rippled
      structures, and show great promise for strain-gauge sensor applications.

PMID- 22378610
TI  - Facile carbon-fluorine bond activation and subsequent functionalisation of 1,1
      difluoroethylene and tetrafluoroethylene promoted by adjacent metal centres.
AB  - The bridging fluoroolefin ligands in the complexes [Ir(2)(CH(3))(CO)(2)(MU
      olefin)(dppm)(2)][OTf] (olefin = tetrafluoroethylene, 1,1-difluoroethylene; dppm
      = MU-Ph(2)PCH(2)PPh(2); OTf(-) = CF(3)SO(3)(-)) are susceptible to facile
      fluoride ion abstraction. Both fluoroolefin complexes react with
      trimethylsilyltriflate (Me(3)SiOTf) to give the corresponding fluorovinyl
      products by abstraction of a single fluoride ion. Although the trifluorovinyl
      ligand is bound to one metal, the monofluorovinyl group is bridging, bound to one
      metal through carbon and to the other metal through a dative bond from fluorine.
      Addition of two equivalents of Me(3)SiOTf to the tetrafluoroethylene-bridged
      species gives the difluorovinylidene-bridged product [Ir(2)(CH(3))(OTf)(CO)(2)(MU
      OTf)(MU-C=CF(2))(dppm)(2)][OTf]. The 1,1-difluoroethylene species is exceedingly
      reactive, reacting with water to give 2-fluoropropene and [Ir(2)(CO)(2)(MU
      OH)(dppm)(2)][OTf] and with carbon monoxide to give [Ir(2)(CO)(3)(MU
      kappa(1):eta(2)-C=CCH(3))(dppm)(2)][OTf] together with two equivalents of HF. The
      trifluorovinyl product [Ir(2)(kappa(1)-C(2)F(3))(OTf)(CO)(2)(MU-H)(MU
      CH(2))(dppm)(2)][OTf], obtained through single C-F bond activation of the
      tetrafluoroethylene-bridged complex, reacts with H(2) to form trifluoroethylene,
      allowing the facile replacement of one fluorine in C(2)F(4) with hydrogen.

PMID- 22378611
TI  - Contribution of hepatic lineage stage-specific donor memory to the differential
      potential of induced mouse pluripotent stem cells.
AB  - Recent studies suggested that induced pluripotent stem cells (iPSCs) retain a
      residual donor cell gene expression, which may impact their capacity to
      differentiate into cell of origin. Here, we addressed a contribution of a lineage
      stage-specific donor cell memory in modulating the functional properties of
      iPSCs. iPSCs were generated from hepatic lineage cells at an early (hepatoblast
      derived, HB-iPSCs) and end stage (adult hepatocyte, AH-iPSCs) of hepatocyte
      differentiation as well as from mouse embryonic fibroblasts (MEFs-iPSCs) using a
      lentiviral vector encoding four pluripotency-inducing factors Oct4, Sox2, Klf4,
      and c-Myc. All resulting iPSC lines acquired iPSCs phenotype as judged by the
      accepted criteria including morphology, expression of pluripotency markers,
      silencing of transducing factors, capacity of multilineage differentiation in
      teratoma assay, and normal diploid karyotype. However, HB-iPSCs were more
      efficient in directed differentiation toward hepatocytic lineage as compared to
      AH-iPSCs, MEF-iPSCs, or mouse embryonic stem cells (mESCs). Extensive comparative
      transcriptome analyses of the early passage iPSCs, donor cells, and mESCs
      revealed that despite global similarities in gene expression patterns between
      generated iPSCs and mESCs, HB-iPSCs retained a transcriptional memory (seven
      upregulated and 17 downregulated genes) typical of the original cells. Continuous
      passaging of HB-iPSCs erased most of these differences including a superior
      capacity for hepatic redifferentiation. These results suggest that retention of
      lineage stage-specific donor memory in iPSCs may facilitate differentiation into
      donor cell type. The identified gene set may help to improve hepatic
      differentiation for therapeutic applications and contribute to the better
      understanding of liver development.

PMID- 22378612
TI  - Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular
      atrial fibrillation-cost analysis.
AB  - BACKGROUND: cost of anticoagulation with dabigatran is largely based on
      estimation of complication rates derived from clinical trials. OBJECTIVE: to
      investigate cost of anticoagulation with dabigatran in comparison with warfarin
      in clinical practice. METHODS: a prospective observational study of patients with
      non-vavular atrial fibrillation (NVAF) referred to anticoagulation clinic.
      Patients were interviewed (4-6 weekly by telephone) about bleeding events. Costs
      of anticoagulation were calculated as: (i) drug cost, (ii) international
      normalised ratio (INR) monitoring cost and (iii) bleeding cost. For cost
      calculation of dabigatran, INR monitoring cost was omitted. RESULTS: a total of
      402 patients were included and followed up for a mean (SD) of 19 (8.1) months.
      Annual cost of anticoagulation was L207.3 and L1,573.5 per patient for warfarin
      and dabigatran, respectively. Drug price constituted 13.6% of the total cost for
      warfarin and 94% for dabigatran. Total cost of anticoagulation to prevent one
      stroke per year was L6,219, L28,086.5 and L25,181 for warfarin, dabigatran 110
      and 150 mg, respectively. CONCLUSION: cost of anticoagulation is mainly driven by
      drug price for dabigatran and quality of INR control for warfarin. Until the
      price of dabigatran is reviewed, warfarin remains suitable for the majority of
      patients with NVAF.

PMID- 22378613
TI  - The prediction of functional decline in older hospitalised patients.
AB  - BACKGROUND: thirty to sixty per cent of older patients experience functional
      decline after hospitalisation, associated with an increase in dependence,
      readmission, nursing home placement and mortality. First step in prevention is
      the identification of patients at risk. OBJECTIVE: to develop and validate a
      prediction model to assess the risk of functional decline in older hospitalised
      patients. DESIGN: development study: cohort study (n = 492). Validation study:
      secondary data analysis of a cohort study (n = 484) in an independent population.
      Both with follow-up after 3 months. Functional decline was defined as a decline
      of at least one point on the Katz ADL index at follow-up compared with pre
      admission status. SETTING: development study: general internal medicine wards of
      two university hospitals and one regional hospital. Validation study: general
      internal wards of an university hospital. SUBJECTS: patients >=65 years acutely
      admitted and hospitalised for at least 48 h. RESULTS: thirty-five per cent of all
      patients in the development cohort and 32% in the validation cohort developed
      functional decline. A four-item model could accurately predict functional decline
      with an AUC of 0.71. At threshold 2 sensitivity, specificity, positive and
      negative predictive values were 87, 39, 43 and 85%, respectively. In the
      validation study, this was, respectively, 0.68, 89, 41, 41 and 89%. CONCLUSION:
      pre-admission need for assistance in instrumental activities of daily living, use
      of a walking device, need for assistance in travelling and no education after age
      14, are the items of a prediction model to identify older patients at risk for
      functional decline following hospital admission. The strength of the model is
      that it relies on four simple questions and this makes it easy to use in clinical
      practice and easy to administer.

PMID- 22378614
TI  - Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a
      rat model.
AB  - Atrophy of the rotator cuff muscles is a factor that complicates the treatment of
      a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern
      the development of muscle atrophy after RCTs have not been well defined. The
      Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role
      in maintaining muscle mass in response to mechanical loading. The role of this
      pathway in the development of muscle atrophy after a massive RCT remains unknown.
      The purpose of this study was to investigate the regulation of the Akt/mTOR
      pathway in the development of muscle atrophy after a RCT and suprascapular nerve
      (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how
      this pathway interacts with two atrophy-related genes, MuRF-1 and MAFbx, in
      supraspinatus muscles of rats that underwent unilateral complete rotator cuff
      tendon transection or SSN transection. Akt/mTOR activity was significantly
      reduced after tendon rupture, but increased after nerve injury. MuRF-1 and MAFbx
      were only up-regulated following denervation. These results suggest that tendon
      transection leads to a decrease in protein synthesis with down-regulation of the
      Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein
      degradation via up-regulation of expression of MuRF-1 and MAFbx.

PMID- 22378616
TI  - Regioselective formation of saturated abnormal NHC-gold(I) complexes by [3+2]
      cycloaddition of azomethine ylides and isonitrile gold(I) complexes.

PMID- 22378615
TI  - Adsorption and separation of light gases on an amino-functionalized metal-organic
      framework: an adsorption and in situ XRD study.
AB  - The NH(2)-MIL-53(Al) metal-organic framework was studied for its use in the
      separation of CO(2) from CH(4), H(2), N(2)C(2)H(6) and C(3)H(8) mixtures.
      Isotherms of methane, ethane, propane, hydrogen, nitrogen, and CO(2) were
      measured. The atypical shape of these isotherms is attributed to the breathing
      properties of the material, in which a transition from a very narrow pore form to
      a narrow pore form and from a narrow pore form to a large pore form occurs,
      depending on the total pressure and the nature of the adsorbate, as demonstrated
      by in situ XRD patterns measured during adsorption. Apart from CO(2), all tested
      gases interacted weakly with the adsorbent. As a result, they are excluded from
      adsorption in the narrow pore form of the material at low pressure. CO(2)
      interacted much more strongly and was adsorbed in significant amounts at low
      pressure. This gives the material excellent properties to separate CO(2) from
      other gases. The separation of CO(2) from methane, nitrogen, hydrogen, or a
      combination of these gases has been demonstrated by breakthrough experiments
      using pellets of NH(2)-MIL-53(Al). The effect of total pressure (1-30 bar), gas
      composition, temperature (303-403 K) and contact time has been examined. In all
      cases, CO(2) was selectively adsorbed, whereas methane, nitrogen, and hydrogen
      nearly did not adsorb at all. Regeneration of the adsorbent by thermal treatment,
      inert purge gas stripping, and pressure swing has been demonstrated. The NH(2)
      MIL-53(Al) pellets retained their selectivity and capacity for more than two
      years.

PMID- 22378617
TI  - Li2 trapped inside tubiform [n] boron nitride clusters (n=4-8): structures and
      first hyperpolarizability.
AB  - The geometries and electronic properties of tubiform [n] boron nitride clusters
      entrapping Li(2) (Li(2)@BN-cluster(n,0); n=4-8), obtained by doping BN
      cluster(n,0) with Li(2) molecules, are investigated by means of DFT. The effects
      of tube diameter n on the dipole moment MU(0), static polarizability alpha(0),
      and first hyperpolarizability beta(0) are elucidated. Both the dipole moment and
      polarizability increase with increasing tube diameter, whereas variation of the
      static first hyperpolarizability with tube diameter is not monotonic; beta(0)
      follows the order 1612 (n=4)<3112 (n=5)<5534 (n=7)<8244 (n=6)<12,282 a.u. (n=8).
      In addition, the natural bond orbital (NBO) charges show that charge transfer
      takes place from the Li(2) molecule to the BN cluster, except for BN-cluster(8,0)
      with larger tube diameter. Since the large-diameter tubular BN-cluster(8,0) can
      trap the excess electrons of the Li(2) molecule, Li(2)@BN-cluster(8,0) can be
      considered to be a novel electride compound.

PMID- 22378618
TI  - Copper-mediated controlled/"living" radical polymerization in polar solvents:
      insights into some relevant mechanistic aspects.
AB  - The field of transition-metal-mediated controlled/"living" radical polymerization
      (CLRP) has become the subject of intense discussion regarding the mechanism of
      this widely-used and versatile process. Most mechanistic analyses (atom transfer
      radical polymerization (ATRP) vs. single-electron transfer living radical
      polymerization (SET-LRP)) have been based on model experiments, which cannot
      correctly mimic the true reaction conditions. We present, for the first time, a
      determination of the [Cu(I)Br]/[L] (L=nitrogen-based chelating ligand) ratio and
      the extent of Cu(I)Br/L disproportionation during CLRP of methyl acrylate (MA) in
      dimethylsulfoxide (DMSO) with Cu(0) wire as a transition-metal catalyst source.
      The results suggest that Cu(0) acts as a supplemental activator and reducing
      agent of Cu(II)Br(2)/L to Cu(I)Br/L. More importantly, the Cu(I)Br/L species seem
      to be responsible for the activation of SET-LRP.

PMID- 22378619
TI  - Converting graphene oxide monolayers into boron carbonitride nanosheets by
      substitutional doping.
AB  - To realize graphene-based electronics, bandgap opening of graphene has become one
      of the most important issues that urgently need to be addressed. Recent
      theoretical and experimental studies show that intentional doping of graphene
      with boron and nitrogen atoms is a promising route to open the bandgap, and the
      doped graphene might exhibit properties complementary to those of graphene and
      hexagonal boron nitride (h-BN), largely extending the applications of these
      materials in the areas of electronics and optics. This work demonstrates the
      conversion of graphene oxide nanosheets into boron carbonitride (BCN) nanosheets
      by reacting them with B(2) O(3)  and ammonia at 900 to 1100  degrees C, by which
      the boron and nitrogen atoms are incorporated into the graphene lattice in
      randomly distributed BN nanodomains. The content of BN in BN-doped graphene
      nanosheets can be tuned by changing the reaction temperature, which in turn
      affects the optical bandgap of these nanosheets. Electrical measurements show
      that the BN-doped graphene nanosheet exhibits an ambipolar semiconductor behavior
      and the electrical bandgap is estimated to be ~25.8 meV. This study provides a
      novel and simple route to synthesize BN-doped graphene nanosheets that may be
      useful for various optoelectronic applications.

PMID- 22378621
TI  - Differential analysis of peripheral blood- and bone marrow-derived endothelial
      progenitor cells for enhanced vascularization in bone tissue engineering.
AB  - For tissue engineering applications, effective bone regeneration requires rapid
      neo-vascularization of implanted grafts to ensure the survival of cells in the
      early post-implantation phase. Incorporation of autologous endothelial progenitor
      cells (EPCs) for the promotion of primitive vascular network formation ex vivo
      has offered great promise for improved graft survival, enhanced rate of
      vascularization and bone regeneration in vivo. For clinical usage, identification
      of an optimal EPC isolation source from the patient is critical. We have, for the
      first time, characterized and directly compared EPCs from rabbit peripheral blood
      and bone marrow (PB-EPCs and BM-EPCs, respectively). PB-EPCs outperformed BM-EPCs
      on all measures. PB-EPCs displayed typical endothelial cell markers, such as
      CD31, as well as high angiogenic potential in three-dimensional extracellular
      matrix in vitro. Furthermore, PB-EPCs cultured simultaneously with mesenchymal
      stem cells, displayed significantly enhanced expression levels of key osteogenic
      and vascular markers, including alkaline phosphatase, bone morphogenetic protein
      2, and vascular endothelial growth factor. On the contrary, putative BM-EPCs did
      not express CD31, and instead, expressed key smooth muscle markers. BM-EPCs
      further failed to display vasculogenic activity. Hence, the highly angiogenic PB
      derived EPCs may serve as an ideal cell population for enhanced vascularization
      and success of engineered bone tissue.

PMID- 22378620
TI  - New aspects of neuroblastoma treatment: ASPHO 2011 symposium review.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood, and the
      outcomes for children with high-risk and relapsed disease remain poor. However,
      new international strategies for risk stratification and for treatment based on
      novel tumor targets and including immunotherapy are being employed in attempts to
      improve the outcomes of children with neuroblastoma. A new international
      neuroblastoma risk classification system has been developed which is being
      incorporated into cooperative group clinical trials in North America, Japan, and
      Europe, resulting in standardized approaches for the initial evaluation and
      treatment stratification of neuroblastoma patients. Furthermore, novel treatment
      regimens are being developed based on improved understanding of neuroblastoma
      biology and on the recruitment of the immune system to specifically target
      neuroblastoma tumors. These approaches will lead to new therapeutic strategies
      that likely will improve the outcomes for children with neuroblastoma worldwide.

PMID- 22378622
TI  - Recurrent twin-twin transfusion syndrome after selective fetoscopic laser
      photocoagulation: a systematic review of the literature.
AB  - OBJECTIVES: Selective fetoscopic laser photocoagulation (SFLP) is now the
      treatment of choice for twin-twin transfusion syndrome (TTTS). The incidence of
      recurrent TTTS following SFLP has been inconsistently reported across different
      studies. We performed a systematic review of TTTS recurrence following SFLP.
      METHODS: PubMed and MEDLINE online databases were searched for articles published
      between 2000 and August 2011, using combinations of the terms 'twin-twin
      transfusion', 'TTTS', 'laser', 'recur' and 'outcome'. Citations identified in the
      primary search were screened for eligibility. Studies reporting outcomes from
      selective SFLP for TTTS in twin pregnancies, which addressed specifically the
      issue of TTTS recurrence, were included. The primary outcome was rate of TTTS
      recurrence. Secondary outcomes were therapeutic preference and fetal outcomes in
      cases of recurrent TTTS. RESULTS: The primary search identified 22 eligible
      studies that are included in this review (n = 2447 twin pregnancies). Two studies
      included a minority of non-selective procedures. The published incidence of
      recurrent TTTS ranged from 0 to 16%. Clinical management was reported in 65.7%
      (71/108) cases, with repeat SFLP the most commonly performed secondary
      intervention. Only three studies provided comprehensive outcome data for cases of
      recurrent TTTS. The overall rate of neurologically-intact survival was 44%
      (23/52). The data were inadequate to determine the effects of secondary
      therapeutic approach, placental location or gestational age on perinatal outcome
      in cases of recurrent TTTS. CONCLUSIONS: The published rate of TTTS recurrence
      following SFLP in monochorionic twin pregnancies ranges from 0 to 16%. Although
      limited follow-up data suggest that recurrence is associated with significant
      perinatal mortality and morbidity, further study is needed. Currently, there are
      insufficient data available to guide recommendations for clinical management of
      TTTS recurrence. Future studies on SFLP for TTTS must include details on
      recurrence rates and provide outcome data specific to the recurrent subset.

PMID- 22378623
TI  - Edge-enriched, porous carbon-based, high energy density supercapacitors for
      hybrid electric vehicles.
AB  - Supercapacitors can store and deliver energy by a simple charge separation, and
      thus they could be an attractive option to meet transient high energy density in
      operating fuel cells and in electric and hybrid electric vehicles. To achieve
      such requirements, intensive studies have been carried out to improve the
      volumetric capacitance in supercapacitors using various types and forms of
      carbons including carbon nanotubes and graphenes. However, conventional porous
      carbons are not suitable for use as electrode material in supercapacitors for
      such high energy density applications. Here, we show that edge-enriched porous
      carbons are the best electrode material for high energy density supercapacitors
      to be used in vehicles as an auxiliary powertrain. Molten potassium hydroxide
      penetrates well-aligned graphene layers vertically and consequently generates
      both suitable pores that are easily accessible to the electrolyte and a large
      fraction of electrochemically active edge sites. We expect that our findings will
      motivate further research related to energy storage devices and also
      environmentally friendly electric vehicles.

PMID- 22378624
TI  - Intramolecularly coordinated organotin tellurides: stable or unstable?
AB  - The step-wise oxidation of an organotin(I) compound with elemental tellurium gave
      a variety of unprecedented organotin tellurides containing tin atoms in the
      oxidation states +II and +IV.

PMID- 22378625
TI  - Graphoepitaxy of block-copolymer self-assembly integrated with single-step ZnO
      nanoimprinting.
AB  - A highly efficient, ultralarge-area nanolithography that integrates block
      copolymer lithography with single-step ZnO nanoimprinting is introduced. The UV
      assisted imprinting of a photosensitive sol-gel precursor creates large-area ZnO
      topographic patterns with various pattern shapes in a single-step process. This
      straightforward approach provides a smooth line edge and high thermal stability
      of the imprinted ZnO pattern; these properties are greatly advantageous for
      further graphoepitaxial block-copolymer assembly. According to the ZnO pattern
      shape and depth, the orientation and lateral ordering of self-assembled
      cylindrical nanodomains in block-copolymer thin films could be directed in a
      variety of ways. Significantly, the subtle tunability of ZnO trench depth enabled
      by nanoimprinting, generated complex hierarchical nanopatterns, where surface
      parallel and surface-perpendicular nanocylinder arrays are alternately arranged.
      The stability of this complex morphology is confirmed by self-consistent field
      theory (SCFT) calculations. The highly ordered graphoepitaxial nanoscale assembly
      achieved on transparent semiconducting ZnO substrates offers enormous potential
      for photonics and optoelectronics.

PMID- 22378626
TI  - Conformational analysis of green apple flavour: the gas-phase structure of ethyl
      valerate validated by microwave spectroscopy.
AB  - We report on the microwave spectrum of ethyl valerate, C(4)H(9)-COO-C(2)H(5),
      observed by molecular beam Fourier transform microwave spectroscopy (MB-FTMW).
      Highly accurate rotational and centrifugal distortion constants of the two most
      abundant conformers were determined. Their structure was investigated by
      comparison of the experimental rotational constants with those obtained by
      quantum chemical calculations. MP2/ 6-311++G(d,p) calculations failed to give a
      proper description of the observed conformers in the supersonic jet. Therefore,
      also other basis sets were tried using Hartree-Fock, second-order Moller-Plesset
      (MP2), and B3LYP methods to predict the observed gas-phase structures of the
      molecule. The quantum chemical results guided the conformer assignment of the
      rotational constants, obtained from the microwave experiment. One of the two
      observed conformers has C(s) symmetry, while the most abundant conformer has C(1)
      symmetry. The main conformer possesses a strong spectrum with high intensities.
      Additionally, harmonic frequency calculations at different levels of theory where
      carried out and a low lying vibration of the entire n-butyl group against the
      rest of the molecule was identified. The symbiotic interplay of microwave gas
      phase investigations and quantum chemical calculations becomes evident in our
      results.

PMID- 22378627
TI  - Circumflex scapular perforator propeller flap for axillary reconstruction.

PMID- 22378629
TI  - Ultrasound-guided radiofrequency ablation of symptomatic uterine fibroids: short
      term evaluation of effect of treatment on quality of life and symptom severity.
AB  - OBJECTIVE: To evaluate the feasibility of ultrasound-guided radiofrequency
      ablation (USgRFA) for the treatment of women with symptomatic uterine fibroids in
      relation to volume of fibroid. METHODS: Forty-three women with symptomatic
      fibroids underwent USgRFA for treatment of uterine fibroids. Improvements in
      fibroid symptoms and quality of life were measured by the Uterine Fibroid Symptom
      and Quality of Life questionnaire scores at baseline and 3, 6 and 9 months after
      the intervention, and analyzed in relation to baseline fibroid volume. Volume
      reduction of fibroids was measured and the frequency of adverse events and re
      interventions was recorded. RESULTS: Following USgRFA, mean Symptom Severity
      Scores (SSS) decreased from 60.7 +/- 17.8 to 31.2 +/- 19.5, corresponding to an
      improvement of 48.6%. The total Health-Related Quality of Life (HRQOL) score
      improved by 46.4% from 55.6 +/- 20.9 to 81.4 +/- 16.6. There was no correlation
      between fibroid volume at baseline and improvement in SSS and HRQOL scores.
      Fibroid volume was reduced in all patients, by a mean of 69.7 +/- 19.4%. Two
      (4.7%) patients underwent hysterectomy. No adverse events occurred. CONCLUSION:
      USgRFA reduces fibroid symptom and size even in patients with larger fibroids.
      USgRFA is a promising new treatment for fibroids in gynecological settings and
      should be further investigated.

PMID- 22378628
TI  - Rhabdomyosarcoma: review of the Children's Oncology Group (COG) Soft-Tissue
      Sarcoma Committee experience and rationale for current COG studies.
AB  - The prognosis for children and adolescents with rhabdomyosarcoma (RMS) has
      improved with refinements in multi-modal therapy. Since 1972, the Intergroup
      Rhabdomyosarcoma Study Group (now the Children's Oncology Group Soft-Tissue
      Sarcoma Committee) has conducted serial studies for RMS. This review describes
      the IRSG and COG experience with RMS, presents the current risk stratification
      definitions, and provides rationale for the current generation of COG RMS
      studies.

PMID- 22378630
TI  - Hydrogen production from glucose and sorbitol by sorption-enhanced steam
      reforming: challenges and promises.
AB  - Concerning energy and environmental sustainability, it is appealing to produce
      hydrogen from sugars or sugar alcohols that are readily obtained from the
      hydrolysis of cellulosic biomass. Nevertheless, the conversion of such compounds
      for hydrogen production poses great technical challenges. In this paper, we
      report that hydrogen purity and yield can be significantly improved by
      integrating in situ CO(2) capture into the steam reforming reaction of the model
      compounds-glucose and sorbitol. The experimental assessment was conducted at a
      steam-to-carbon ratio of 1.8 for sorbitol and 6 for glucose from 450-625  degrees
      C. As predicted by thermodynamic analysis, combining CO(2) capture and reforming
      reactions at favorable operating conditions yielded very high purity hydrogen,
      for instance, 98.8 mol % from sorbitol and 99.9 mol % from glucose. However,
      there are trade-offs between hydrogen purity and yield in practice. The lower
      operating temperatures in the examined range helped to increase the hydrogen
      purity and reduce the CO content in the gas product, whereas a high hydrogen
      yield was more likely to be obtained at higher temperatures. Coupling CO(2)
      capture lowered the risk of coke formation during the steam reforming of glucose.
      Coke accumulated in the reactor for the sorption-enhanced steam reforming of
      glucose was mostly from the slow pyrolysis of glucose before it came into contact
      with the catalyst-acceptor bed. This problem may be solved by improving heat
      transfer or reconstructing the reactor, for instance, by using a fluidized-bed
      reactor.

PMID- 22378631
TI  - Lack of prognostic significance of absolute lymphocyte count after intensive
      induction therapy in childhood acute lymphoblastic leukemia.

PMID- 22378633
TI  - Phase behaviour, interactions, and structural studies of (amines+ionic liquids)
      binary mixtures.
AB  - We present a study on the phase equilibrium behaviour of binary mixtures
      containing two 1-alkyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}imide
      based ionic liquids, [C(n)mim] [NTf(2)] (n=2 and 4), mixed with diethylamine or
      triethylamine as a function of temperature and composition using different
      experimental techniques. Based on this work, two systems showing an LCST and one
      system with a possible hourglass shape are measured. Their phase behaviours are
      then correlated and predicted by using Flory-Huggins equations and the UNIQUAC
      method implemented in Aspen. The potential of the COSMO-RS methodology to predict
      the phase equilibria was also tested for the binary systems studied. However,
      this methodology is unable to predict the trends obtained experimentally,
      limiting its use for systems involving amines in ionic liquids. The liquid-state
      structure of the binary mixture ([C(2)mim] [NTf(2)]+diethylamine) is also
      investigated by molecular dynamics simulation and neutron diffraction. Finally,
      the absorption of gaseous ethane by the ([C(2)mim][NTf(2)]+diethylamine) binary
      mixture is determined and compared with that observed in the pure solvents.

PMID- 22378634
TI  - Reversible single-molecule switching in an ordered monolayer molecular dipole
      array.
AB  - Making electronic devices using a single molecule has been the ultimate goal of
      molecular electronics. For binary data storage in particular, the challenge has
      been the ability to switch a single molecule in between bistable states in a
      simple and repeatable manner. The reversible switching of single molecules of
      chloroaluminum phthalocyanine (ClAlPc) dipolar molecules within a close-packed
      monolayer is demonstrated. By pulsing an scanning tunneling microscopy tip, read
      write operations of single-molecular binary bits at ~40 Tb/cm(2) (~250 Tb/in(2))
      are demonstrated.

PMID- 22378635
TI  - Enhanced electrocatalytic stability of platinum nanoparticles supported on a
      nitrogen-doped composite of carbon nanotubes and mesoporous titania under oxygen
      reduction conditions.
AB  - Cheers for titania: An N-doped composite of carbon nanotubes (CNTs) and
      mesoporous TiO(2) is used as support for Pt nanoparticles applied in the oxygen
      reduction reaction. The composite Pt/N-TiO(2) -CNT shows a higher stability than
      Pt particles on carbon black or N-doped CNTs, as indicated by accelerated stress
      tests of up to 2000 cycles. The enhanced stability is attributed to strong
      interactions between TiO(2) and Pt and a higher corrosion resistance of TiO(2) as
      well as CNTs.

PMID- 22378636
TI  - Differential regulation of mesodermal gene expression by Drosophila cell type
      specific Forkhead transcription factors.
AB  - A common theme in developmental biology is the repeated use of the same gene in
      diverse spatial and temporal domains, a process that generally involves
      transcriptional regulation mediated by multiple separate enhancers, each with its
      own arrangement of transcription factor (TF)-binding sites and associated
      activities. Here, by contrast, we show that the expression of the Drosophila
      Nidogen (Ndg) gene at different embryonic stages and in four mesodermal cell
      types is governed by the binding of multiple cell-specific Forkhead (Fkh) TFs -
      including Biniou (Bin), Checkpoint suppressor homologue (CHES-1-like) and Jumeau
      (Jumu) - to three functionally distinguishable Fkh-binding sites in the same
      enhancer. Whereas Bin activates the Ndg enhancer in the late visceral
      musculature, CHES-1-like cooperates with Jumu to repress this enhancer in the
      heart. CHES-1-like also represses the Ndg enhancer in a subset of somatic
      myoblasts prior to their fusion to form multinucleated myotubes. Moreover,
      different combinations of Fkh sites, corresponding to two different sequence
      specificities, mediate the particular functions of each TF. A genome-wide scan
      for the occurrence of both classes of Fkh domain recognition sites in association
      with binding sites for known cardiac TFs showed an enrichment of combinations
      containing the two Fkh motifs in putative enhancers found within the noncoding
      regions of genes having heart expression. Collectively, our results establish
      that different cell-specific members of a TF family regulate the activity of a
      single enhancer in distinct spatiotemporal domains, and demonstrate how
      individual binding motifs for a TF class can differentially influence gene
      expression.

PMID- 22378637
TI  - Cell movements of the deep layer of non-neural ectoderm underlie complete neural
      tube closure in Xenopus.
AB  - In developing vertebrates, the neural tube forms from a sheet of neural ectoderm
      by complex cell movements and morphogenesis. Convergent extension movements and
      the apical constriction along with apical-basal elongation of cells in the neural
      ectoderm are thought to be essential for the neural tube closure (NTC) process.
      In addition, it is known that non-neural ectoderm also plays a crucial role in
      this process, as the neural tube fails to close in the absence of this tissue in
      chick and axolotl. However, the cellular and molecular mechanisms by which it
      functions in NTC are as yet unclear. We demonstrate here that the non-neural
      superficial epithelium moves in the direction of tensile forces applied along the
      dorsal-ventral axis during NTC. We found that this force is partly attributable
      to the deep layer of non-neural ectoderm cells, which moved collectively towards
      the dorsal midline along with the superficial layer. Moreover, inhibition of this
      movement by deleting integrin beta1 function resulted in incomplete NTC.
      Furthermore, we demonstrated that other proposed mechanisms, such as oriented
      cell division, cell rearrangement and cell-shape changes have no or only minor
      roles in the non-neural movement. This study is the first to demonstrate dorsally
      oriented deep-cell migration in non-neural ectoderm, and suggests that a global
      reorganization of embryo tissues is involved in NTC.

PMID- 22378639
TI  - Drosophila miR-124 regulates neuroblast proliferation through its target
      anachronism.
AB  - MicroRNAs (miRNAs) have been implicated as regulators of central nervous system
      (CNS) development and function. miR-124 is an evolutionarily ancient, CNS
      specific miRNA. On the basis of the evolutionary conservation of its expression
      in the CNS, miR-124 is expected to have an ancient conserved function.
      Intriguingly, investigation of miR-124 function using antisense-mediated miRNA
      depletion has produced divergent and in some cases contradictory findings in a
      variety of model systems. Here we investigated miR-124 function using a targeted
      knockout mutant and present evidence for a role during central brain neurogenesis
      in Drosophila melanogaster. miR-124 activity in the larval neuroblast lineage is
      required to support normal levels of neuronal progenitor proliferation. We
      identify anachronism (ana), which encodes a secreted inhibitor of neuroblast
      proliferation, as a functionally important target of miR-124 acting in the
      neuroblast lineage. ana has previously been thought to be glial specific in its
      expression and to act from the cortex glia to control the exit of neuroblasts
      from quiescence into the proliferative phase that generates the neurons of the
      adult CNS during larval development. We provide evidence that ana is expressed in
      miR-124-expressing neuroblast lineages and that ana activity must be limited by
      the action of miR-124 during neuronal progenitor proliferation. We discuss the
      possibility that the apparent divergence of function of miR-124 in different
      model systems might reflect functional divergence through target site evolution.

PMID- 22378638
TI  - The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male
      germline stem cells and the niche.
AB  - The stem cell niche provides a supportive microenvironment to maintain adult stem
      cells in their undifferentiated state. Adhesion between adult stem cells and
      niche cells or the local basement membrane ensures retention of stem cells in the
      niche environment. Drosophila male germline stem cells (GSCs) attach to somatic
      hub cells, a component of their niche, through E-cadherin-mediated adherens
      junctions, and orient their centrosomes toward these localized junctional
      complexes to carry out asymmetric divisions. Here we show that the transmembrane
      receptor tyrosine phosphatase Leukocyte-antigen-related-like (Lar), which is best
      known for its function in axonal migration and synapse morphogenesis in the
      nervous system, helps maintain GSCs at the hub by promoting E-cadherin-based
      adhesion between hub cells and GSCs. Lar is expressed in GSCs and early
      spermatogonial cells and localizes to the hub-GSC interface. Loss of Lar function
      resulted in a reduced number of GSCs at the hub. Lar function was required cell
      autonomously in germ cells for proper localization of Adenomatous polyposis coli
      2 and E-cadherin at the hub-GSC interface and for the proper orientation of
      centrosomes in GSCs. Ultrastructural analysis revealed that in Lar mutants the
      adherens junctions between hub cells and GSCs lack the characteristic dense
      staining seen in wild-type controls. Thus, the Lar receptor tyrosine phosphatase
      appears to polarize and retain GSCs through maintenance of localized E-cadherin
      based adherens junctions.

PMID- 22378640
TI  - Control of embryonic meristem initiation in Arabidopsis by PHD-finger protein
      complexes.
AB  - Plant growth is directed by the activity of stem cells within meristems. The
      first meristems are established during early embryogenesis, and this process
      involves the specification of both stem cells and their organizer cells. One of
      the earliest events in root meristem initiation is marked by re-specification of
      the uppermost suspensor cell as hypophysis, the precursor of the organizer. The
      transcription factor MONOPTEROS (MP) is a key regulator of hypophysis
      specification, and does so in part by promoting the transport of the plant
      hormone auxin and by activating the expression of TARGET OF MP (TMO)
      transcription factors, both of which are required for hypophysis specification.
      The mechanisms leading to the activation of these genes by MP in a chromatin
      context are not understood. Here, we show that the PHD-finger proteins OBERON
      (OBE) and TITANIA (TTA) are essential for MP-dependent embryonic root meristem
      initiation. TTA1 and TTA2 are functionally redundant and function in the same
      pathway as OBE1 and OBE2. These PHD-finger proteins interact with each other, and
      genetic analysis shows that OBE-TTA heterotypic protein complexes promote
      embryonic root meristem initiation. Furthermore, while MP expression is
      unaffected by mutations in OBE/TTA genes, expression of MP targets TMO5 and TMO7
      is locally lost in obe1 obe2 embryos. PHD-finger proteins have been shown to act
      in initiation of transcription by interacting with nucleosomes. Indeed, we found
      that OBE1 binds to chromatin at the TMO7 locus, suggesting a role in its MP
      dependent activation. Our data indicate that PHD-finger protein complexes are
      crucial for the activation of MP-dependent gene expression during embryonic root
      meristem initiation, and provide a starting point for studying the mechanisms of
      developmental gene activation within a chromatin context in plants.

PMID- 22378641
TI  - Imatinib mesylate causes growth deceleration in pediatric patients with chronic
      myelogenous leukemia.
AB  - BACKGROUND: Imatinib mesylate, a tyrosine kinase inhibitor, is used in the
      treatment of chronic myelogeneous leukemia (CML). Given its ease of
      administration and manageable side effects in adults, imatinib mesylate was
      introduced as therapy for pediatric CML. Recently published case reports describe
      growth deceleration in children treated with imatinib. This study details the
      growth phenotype of seven pediatric patients maintained in remission on imatnib
      mesylate over an extended period of time. PROCEDURE: This study is a
      retrospective chart review of pediatric patients with CML at Oregon Health &
      Science University treated with imatinib. Height, weight, and body mass index
      (BMI) measurements were collected before and during treatment. Median standard
      deviation scores (SDS) were analyzed by Wilcoxon Rank-Sum test and Wilcoxon
      signed rank cohort analysis. RESULTS: Individual patient analysis demonstrated
      five of seven subjects with a statistically significant decrease in height SDS
      pre versus during treatment. The whole group analysis showed a trend to
      significance for difference in median height SDS pre and during treatment (P =
      0.078). Bone age was delayed in all four patients in whom bone ages were
      obtained. IGF-1, IGFBP-3, and thyroid levels during treatment were normal. Four
      patients experienced an improvement in height SDS during puberty. However, three
      patients approaching near final adult height failed to achieve genetic height
      potential determined by mid-parental target height. CONCLUSION: Growth in
      children with CML appears to be adversely impacted by imatinib therapy. BMI and
      IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of
      imatinib on the growth plate.

PMID- 22378642
TI  - Total synthesis of RNA-polymerase inhibitor ripostatin B and 15-deoxyripostatin
      A.
AB  - Keep me skipped: a highly convergent total synthesis of ripostatin B, an
      inhibitor of the bacterial RNA polymerase, is described. The key steps to
      construct and avoid isomerization of the skipped triene are a double Stille cross
      coupling reaction and a ring-closing metathesis. Furthermore, 15-deoxyripostatin
      A, a stable and conformationally locked analogue of ripostatin A, was prepared
      and tested in vivo.

PMID- 22378643
TI  - Structures and reactivity of oxygen-rich scandium cluster anions ScO(3-5)-.
AB  - Oxygen-rich scandium cluster anions ScO(3-5)(-) are prepared by laser ablation
      and allowed to react with n-butane in a fast-flow reactor. A time-of-flight mass
      spectrometer is used to detect the cluster distribution before and after the
      reactions. The ScO(3)(-) and ScO(4)(-) clusters can react with n-butane to
      produce ScO(3)H(-), ScO(3)H(2)(-), and ScO(4)H(-), while the more oxygen-rich
      cluster ScO(5)(-) is inert. The experiment suggests that unreactive cluster
      isomers of ScO(3)(-) and ScO(4)(-) are also present in the cluster source.
      Density functional theory and ab initio methods are used to calculate the
      structures and reaction mechanisms of the clusters. The theoretical results
      indicate that the unreactive and reactive cluster isomers of ScO(3,4)(-) contain
      peroxides (O(2)(2-)) and oxygen-centered radicals (O(.-)), respectively. The
      mechanisms and energetics for conversion of unreactive O(2)(2-) to reactive O(.-)
      species are also theoretically studied.

PMID- 22378644
TI  - Highly permeable and selective pore-spanning biomimetic membrane embedded with
      aquaporin Z.
AB  - A highly permeable yet highly selective pore-spanning biomimetic membrane
      embedded with aquaporin Z is molecularly designed and constructed via a
      combination of pressure-assisted vesicle adsorption and covalent-conjugation
      driven vesicle fusion on a porous support. This approach represents a significant
      breakthrough in the architecture of biomimetic membranes embedded with aquaporin
      in a planar form.

PMID- 22378645
TI  - Synthesis of functional acetylene derivatives from calcium carbide.
AB  - AHA Erlebnis: CaC(2), used to produce acetylene until several decades ago, is re
      emerging as a cheap, sustainable resource synthesized from coal and
      lignocellulosic biomass. We report efficient catalytic protocols for the
      synthesis of functional acetylene derivatives from CaC(2) through aldehyde,
      alkyne, and amine (AAA) as well as alkyne, haloalkane, and amine (AHA) couplings,
      and in addition demonstrate its use in click and Sonogashira chemistry, showing
      that calcium carbide is a sustainable and cost-efficient carbon source.

PMID- 22378647
TI  - Timely plant defenses protect against caterpillar herbivory.

PMID- 22378648
TI  - Surficial redistribution of fallout 131iodine in a small temperate catchment.
AB  - Isotopes of iodine play significant environmental roles, including a limiting
      micronutrient ((127)I), an acute radiotoxin ((131)I), and a geochemical tracer
      ((129)I). But the cycling of iodine through terrestrial ecosystems is poorly
      understood, due to its complex environmental chemistry and low natural abundance.
      To better understand iodine transport and fate in a terrestrial ecosystem, we
      traced fallout (131)iodine throughout a small temperate catchment following
      contamination by the 11 March 2011 failure of the Fukushima Daiichi nuclear power
      facility. We find that radioiodine fallout is actively and efficiently scavenged
      by the soil system, where it is continuously focused to surface soils over a
      period of weeks following deposition. Mobilization of historic (pre-Fukushima)
      (137)cesium observed concurrently in these soils suggests that the focusing of
      iodine to surface soils may be biologically mediated. Atmospherically deposited
      iodine is subsequently redistributed from the soil system via fluvial processes
      in a manner analogous to that of the particle-reactive tracer (7)beryllium, a
      consequence of the radionuclides' shared sorption affinity for fine, particulate
      organic matter. These processes of surficial redistribution create iodine
      hotspots in the terrestrial environment where fine, particulate organic matter
      accumulates, and in this manner regulate the delivery of iodine nutrients and
      toxins alike from small catchments to larger river systems, lakes and estuaries.

PMID- 22378650
TI  - ARRDC1 as a mediator of microvesicle budding.

PMID- 22378652
TI  - Gating mechanism of a P2X4 receptor developed from normal mode analysis and
      molecular dynamics simulations.
AB  - P2X receptors are trimeric ATP-gated cation channels participating in diverse
      physiological processes. How ATP binding triggers channel opening remains
      unclear. Here the gating mechanism of a P2X receptor was studied by normal mode
      analysis and molecular dynamics (MD) simulations. Based on the resting-state
      crystal structure, a normal mode involving coupled motions of three beta-strands
      (beta1, beta13, and beta14) at the trimeric interface of the ligand-binding
      ectodomain and the pore-lining helix (TM2) in the transmembrane domain (TMD) was
      identified. The resulting widening of the fenestrations above the TMD and opening
      of the transmembrane pore produce known signatures of channel activation. In MD
      simulations, ATP was initially placed in the putative binding pocket (defined by
      four charged residues located in beta1, beta13 and beta14) in two opposite
      orientations, with the adenine either proximal or distal to the TMD. In the
      proximal orientation, the triphosphate group extends outward to draw in the four
      charged residues, leading to closure of beta13/beta14 toward beta1. The adenine
      ring, wedged between beta1 and beta13, acts as a fulcrum for the beta14 lever,
      turning a modest closure around the triphosphate group into significant opening
      of the pre-TM2 loop. The motions of these beta-strands are similar to those in
      the putative channel-activation normal mode. In the distal orientation, the ATP
      stabilizes the trimeric interface and the closure of the pre-TM2 loop, possibly
      representing desensitization. Our computational studies produced the first
      complete model, supported by experimental data, for how ATP binding triggers
      activation of a P2X receptor.

PMID- 22378651
TI  - Two copies of the SecY channel and acidic lipids are necessary to activate the
      SecA translocation ATPase.
AB  - The SecA ATPase associates with the SecY complex to push preproteins across the
      bacterial membrane. Because a single SecY is sufficient to create the conducting
      channel, the function of SecY oligomerization remains unclear. Here, we have
      analyzed the translocation reaction using nanodiscs. We show that one SecY copy
      is sufficient to bind SecA and the preprotein, but only the SecY dimer together
      with acidic lipids supports the activation of the SecA translocation ATPase. In
      discs, the dimer is predominantly arranged in a back-to-back manner and remains
      active even if a constituent SecY copy is defective for SecA binding. In membrane
      vesicles and in intact cells, the coproduction of two inactive SecYs, one for
      channel gating and the other for SecA binding, recreates a functional
      translocation unit. These results indisputably argue that the SecY dimer is
      crucial for the activation of SecA, which is necessary for preprotein transport.

PMID- 22378653
TI  - Laryngotracheal reconstruction with resorbable microplate buttressing.
AB  - OBJECTIVES/HYPOTHESIS: In patients undergoing laryngotracheal reconstruction
      (LTR), malacic segments of trachea can pose challenges to successful
      reconstruction. Malacic segments may inadequately support cartilage grafts used
      in augmentation surgery, sometimes requiring cricotracheal or tracheal
      resections. We describe a novel technique of LTR with resorbable microplate
      buttressing of malacic lateral tracheal segments. STUDY DESIGN: Retrospective
      case series. METHODS: Review of technique, treatment outcomes, and complications
      of seven children with subglottic stenosis and tracheomalacia requiring a
      microplate-augmented LTR technique. RESULTS: Seven infants ranging from 26 months
      to 9 years of age successfully underwent LTR for subglottic stenosis. Six
      children had a grade III subglottic stenosis. The seventh child had grade II
      subglottic stenosis, bilateral vocal fold paralysis, an elliptical cricoid, and
      an obstructing giant suprastomal fibroma. Five children underwent a double-stage
      LTR with resorbable microplates sutured bilaterally to support severely malacic
      lateral tracheal segments. A cricotracheal resection would not have been feasible
      in one child due to the resection length and inadequate tracheal mobilization.
      Two children underwent a single-stage LTR with unilateral application of a
      microplate. Six children were decannulated within 3 months and continue without
      airway symptoms or complications. One child, who is just over 2 months from
      reconstructive surgery, is being setup for decannulation. No complications were
      encountered. CONCLUSIONS: LTR with resorbable microplate buttressing of malacic
      lateral tracheal segments is technically feasible, safe, and can avoid more
      extensive surgery requiring tracheal resection. Further experience may support
      the use of this technique in challenging airway reconstructions.

PMID- 22378654
TI  - An iron(III)-monoamidate complex catalyst for selective hydroxylation of alkane C
      H bonds with hydrogen peroxide.
AB  - Selective oxidation: the success of the title reaction is caused by the strong
      electron donation from the amidate moiety of the dpaq ligand to the iron center
      (dpaq=2-[bis(pyridin-2-ylmethyl)]amino-N-quinolin-8-yl-acetamidate). This process
      facilitates the O-O bond heterolysis of the intermediate Fe(III)OOH species to
      generate a selective oxidant without forming highly reactive hydroxyl radicals.

PMID- 22378656
TI  - Brain single-photon emission computed tomography in fetal alcohol syndrome: a
      case report and study implications.
AB  - The indications of brain single-photon emission computed tomography (SPECT) in
      fetal alcohol syndrome are not clearly defined, even though the condition is
      recognized as one of the most common causes of mental retardation. This article
      reports a case of a 9-year-old adopted girl with developmental delay, mildly
      dysmorphic facial features, and behavioral and cognitive abnormalities. Extensive
      investigations including genetic studies and brain magnetic resonance imaging
      (MRI) revealed no abnormalities, and a diagnosis of fetal alcohol syndrome was
      considered since official diagnostic criteria were met. A brain SPECT was
      requested and showed severely decreased tracer activity in the thalami, basal
      ganglia, and temporal lobes on both sides, the overall findings being consistent
      with the established diagnosis of fetal alcohol syndrome. With increasing
      availability of functional brain imaging, the study indications and possible
      ethical implications in suspected prenatal alcohol exposure or even before
      adoption need further consideration. In this patient, SPECT was the only test to
      yield positive results.

PMID- 22378655
TI  - FLT3 mutation status is a predictor of early death in pediatric acute
      promyelocytic leukemia: a report from the Children's Oncology Group.
AB  - BACKGROUND: FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are
      associated with early relapse. The prevalence and prognostic significance of
      FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia
      (APL). PROCEDURE: Diagnostic specimens from 104 pediatric APL patients were
      screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with
      disease characteristics and clinical outcome for patients treated on CALGB C9710
      (n = 50). RESULTS: Forty-two of the 104 patients (40%) had either FLT3/ITD (n =
      28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400
      cells/ul vs. 3,600 cells/ul for those with and without FLT3/Mut (P < 0.001), and
      similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In
      patients treated on C9710, presence of a FLT3 mutation was highly correlated with
      diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P =
      0.035), and a lower remission rate (P = 0.009). In patients who received ATRA
      (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of
      30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P = 0.005). In patients
      with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher
      risk of induction death versus FLT3/WT patients (47% vs. 0%, P = 0.05). FLT3/Mut
      was not associated with adverse outcome in those who survived induction therapy.
      CONCLUSIONS: FLT3/Mut are prevalent in pediatric APL and are associated with high
      WBC count and increased induction death. This study provides further evidence for
      testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in
      this disease.

PMID- 22378657
TI  - Effect of melatonin on seizure frequency in intractable epilepsy: a pilot study.
AB  - Melatonin is effective for treating sleep-wake cycle disturbances and has been
      reported occasionally to decrease epileptic seizure frequency, with no long-term
      side effects. In this pilot study, the investigators examined the effect of
      melatonin on seizures, sleep quality, and behavior in 10 patients aged 9 to 32
      years with intractable epilepsy. Patients were randomized to receive melatonin
      (10 mg daily at bedtime) followed by placebo or placebo followed by melatonin for
      3 weeks each, with a 1-week washout period in between. Seizure frequency was
      monitored by daily diaries and actigraphy recordings; behavioral and sleep
      parameters were rated by caregivers. Diurnal seizures decreased significantly
      with melatonin compared with placebo (P = .034, Wilcoxon test). Maximal number of
      seizures, seizure duration, sleep efficiency or latency, and behavioral
      parameters remained unchanged. No major side effects or seizure aggravation were
      documented. It is concluded that melatonin could be effective and safe for
      decreasing daytime seizure frequency in patients with intractable epilepsy.

PMID- 22378658
TI  - Novel assessment of cortical response to somatosensory stimuli in children with
      hemiparetic cerebral palsy.
AB  - The brain's response to somatosensory stimuli is essential to experience-driven
      learning in children. It was hypothesized that advances in event-related
      potential technology could quantify the response to touch in somatosensory
      cortices and characterize the responses of hemiparetic children. In this
      prospective study of 8 children (5-8 years old) with hemiparetic cerebral palsy,
      both event-related potential responses to sham or air puff trials and standard
      functional assessments were used. Event-related potential technology consistently
      measured signals reflecting activity in the primary and secondary somatosensory
      cortices as well as complex cognitive processing of touch. Participants showed
      typical early responses but less efficient perceptual processes. Significant
      differences between affected and unaffected extremities correlated with
      sensorimotor testing, stereognosis, and 2-point discrimination (r > 0.800 and P =
      .001 for all). For the first time, a novel event-related potential paradigm shows
      that hemiparetic children have slower and less efficient tactile cortical
      perception in their affected extremities.

PMID- 22378659
TI  - Active comparator-controlled, rater-blinded study of corticotropin-based
      immunotherapies for opsoclonus-myoclonus syndrome.
AB  - To test the efficacy and safety of corticotropin-based immunotherapies in
      pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone
      or with intravenous immunoglobulin (groups 1 and 2, active controls); or both
      with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus
      chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in
      motor severity score across groups (P < .0001), but treatment combinations were
      more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded
      better than group 1; groups 3 and 5 responded better than group 2. The response
      frequency to corticotropin was higher than to prior corticosteroids (P < .0001).
      Fifty-five percent had adverse events (corticosteroid excess), more so with
      multiagents (P = .03); and 10% had serious adverse events. This study
      demonstrates greater efficacy of corticotropin-based multimodal therapy compared
      with conventional therapy, greater response to corticotropin than corticosteroid
      based therapy, and overall tolerability.

PMID- 22378660
TI  - Case report of pyruvate dehydrogenase deficiency with unusual increase of fats
      during ketogenic diet treatment.
AB  - This article describes a case of pyruvate dehydrogenase deficiency in a 3-year
      old boy who presented generalized hypotonia, severe psychomotor development
      delay, and generalized and partial seizures and was refractory to antiepileptic
      drugs. After the diagnosis, the patient was put on a ketogenic diet. Six months
      later, seizure frequency was reduced and psychomotor development had improved. At
      the same time he presented some side effects, such as 2 episodes of significant
      increases in cholesterol and triglycerides associated with viral respiratory
      infections. The latter decreased with a supplementation of omega-3 fatty acids
      and an increase in caloric intake.

PMID- 22378661
TI  - Pitt-Hopkins syndrome in a boy with Charcot Marie Tooth disease type 1A: a rare
      co-occurrence of 2 genetic disorders.
AB  - Pitt-Hopkins syndrome is characterized by marked intellectual impairment,
      hyperventilation episodes, and dysmorphic facial features. This article reports a
      boy who presented with developmental delay, facial dysmorphism, microcephaly,
      hypotonia, and areflexia. He was initially diagnosed with Charcot Marie Tooth
      disease type 1A based on family history and genetic testing. However, severe
      mental impairment was atypical of Charcot Marie Tooth disease type 1A. Over the
      next few years he developed characteristic breathing abnormality, hand
      stereotypies, seizures, and marked constipation. The evolution of these
      manifestations coupled with the characteristic facial appearance suggested the
      additional diagnosis of Pitt-Hopkins syndrome, which was confirmed by the genetic
      defect of the transcription factor 4 on chromosome 18. This case demonstrates the
      rare co-occurrence of 2 genetic disorders in the same individual.

PMID- 22378662
TI  - Clinical and polygraphic improvement of breathing abnormalities after valproate
      in a case of Pitt-Hopkins syndrome.
AB  - Pitt-Hopkins syndrome is a rare genetic form of severe psychomotor delay, caused
      by mutations in transcription cell factor-4 gene and characterized by distinctive
      dysmorphic features and abnormal breathing pattern. The current report describes
      the polygraphic features of the syndrome's typical breathing pattern in a patient
      both in wakefulness and in sleep. The control of these breathing alterations is
      important to prevent the neurological sequelae linked to chronic cerebral
      hypoxemia in early ages. No data are available on effective treatment options for
      breathing abnormalities of Pitt-Hopkins syndrome. The authors polygraphically
      documented a reduction of apneic and hypopneic phenomena, with a significant
      improvement in saturation values, after the introduction of sodium valproate.

PMID- 22378663
TI  - An 11-year follow-up study of neonatal-onset, bath-induced alternating hemiplegia
      of childhood in twins.
AB  - The authors previously reported on the initial manifestations in a set of female
      twins, who presented soon after birth with bath-induced paroxysmal events each
      time they were immersed in a warm water bath. These episodes progressively ceased
      by the age of 36 months, replaced by paroxysmal episodes of alternating
      hemiplegia unrelated to water immersion. By age 4 years, the twins developed the
      classic features of alternating hemiplegia of childhood. Clinical outcomes at the
      age of 11 years are now reported. Standard and video-electroencephalograms showed
      a large, slow background activity followed by lower amplitude waves without focal
      abnormalities or other abnormal findings. This represents the first report on (a)
      alternating hemiplegia of childhood started with bath-induced paroxysmal
      episodes; (b) this condition in monozygotic twins; and (c) an 11-year follow-up
      study in which the twins continue to experience episodes of alternating
      hemiplegia in the setting of baseline cognitive impairment without epileptic
      episodes.

PMID- 22378664
TI  - In God's image? The tradition of infant head shaping.
AB  - Intentional modification of the infant's head has been commonly practiced at all
      times and in virtually every region of the inhabited world. Motives included
      aesthetic perception of the human head, greater attractiveness, symbolization of
      ethnic identity, demonstration of noble origin or sociocultural status, and
      supposed health benefits. The desired shape was achieved by repeated hand
      massage, or by using devices like cradleboards, which were applied throughout
      infancy. In some regions, infant head shaping was the rule rather than the
      exception. Whereas chronic modification of the skull during the first year of
      life had no adverse effects, one-time postnatal head shaping by the midwife was a
      dangerous procedure. Recommended by Soran in the second century CE, it remained
      in practice for 17 centuries. With the advent of positional plagiocephaly
      following the back-to-sleep campaign, head shaping has regained acceptance and is
      now being widely used again.

PMID- 22378665
TI  - Epilepsy in children--when should we think neurometabolic disease?
AB  - Seizures are often the first manifestation of central nervous system dysfunction
      and are common in many inborn errors of metabolism, especially in neonates,
      infants, and children. A high index of suspicion is required to diagnose inborn
      errors of metabolism as the cause of seizures. It is also important to recognize
      these metabolic disorders early, as specific disease-modifying treatments are
      available for some with favorable long-term outcomes. This review discusses the
      classification of metabolic disorders as a cause of seizures based on
      pathogenesis and age and proposes a tiered approach for cost-effective diagnosis
      of metabolic disorders.

PMID- 22378666
TI  - Peripheral nerve involvement in fukuyama congenital muscular dystrophy: a case
      report.
AB  - Fukuyama congenital muscular dystrophy is characterized by generalized muscle
      weakness and disturbances in central nervous system migration. Although this
      disorder is caused by mutations in the fukutin gene, which encodes a protein
      associated with the hypoglycosylation of alpha-dystroglycan, the specific
      functions of fukutin protein are largely unknown. In addition to being found in
      muscle and brain, alpha-dystroglycan is expressed in various other tissues
      including peripheral nerves, suggesting that deficiencies in fukutin may result
      in abnormal myelination of peripheral nerves due to the aberrant glycosylation of
      Schwann cell alpha-dystroglycan. This report describes a 7-year-old girl with
      Fukuyama congenital muscular dystrophy and demyelinating peripheral
      polyneuropathy.

PMID- 22378667
TI  - Rapidly progressive primary leptomeningeal atypical teratoid/rhabdoid tumor: a
      report of 2 cases.
AB  - Atypical teratoid/rhabdoid tumor is a rare, highly malignant central nervous
      system tumor most commonly occurring in very young children. Atypical
      teratoid/rhabdoid tumor most often presents as an expanding mass with symptoms
      consistent with the location of the tumor and may present with metastatic
      leptomeningeal disease. The authors describe 2 cases of rapidly progressive,
      diffuse leptomeningeal atypical teratoid/rhabdoid tumor without a solid primary
      mass. These cases demonstrate a clinical picture that can easily be confused with
      a basilar meningitis, encephalomyelitis, or vasculitis.

PMID- 22378668
TI  - Is the test of variables of attention reliable for the diagnosis of attention
      deficit hyperactivity disorder (ADHD)?
AB  - The diagnosis of attention-deficit hyperactivity disorder (ADHD) is occasionally
      biased by the subjectivity of symptoms and reports of parents and teachers. The
      advent of continuous performance tests raised expectations that the diagnosis of
      ADHD will be more standardized and accurate. In this study, the authors looked
      for the validity of the ADHD scores obtained by the Test of Variables of
      Attention in 230 children who were referred to their ADHD clinic between 2005 and
      2007. Based on clinical evaluations, 179 children were diagnosed with affirmed or
      suspected ADHD. Among the 179 children with ADHD, the Test of Variables of
      Attention was suggestive of ADHD in 163 participants (91.1% sensitivity), but it
      was also suggestive for ADHD in 78.4% of the children without ADHD. With a low
      specificity of 21.6%, the authors feel that the Test of Variables of Attention is
      not reliable enough to serve as a screening diagnostic tool for ADHD.

PMID- 22378669
TI  - Association between peroxisomal biogenesis factor 7 and autism spectrum disorders
      in a Korean population.
AB  - Autism spectrum disorder is a neurodevelopmental disorder characterized by
      deficits in social communication, impaired reciprocal social interaction, and
      repetitive patterns of behaviors or interests. Although the cause of autism
      spectrum disorder remains elusive, the present study identified peroxisomal
      biogenesis factor 7 (PEX7) as a gene associated with autism spectrum disorder,
      and this association was examined in a Korean population. PEX7 encodes a
      cytosolic receptor for peroxisome targeting signal 2 of peroxisomal matrix
      enzymes that are targeted to and translocated into the peroxisome. PEX7 defects
      are associated with rhizomelic chondrodysplasia punctata type 1 and Refsum
      disease. Mutations in PEX7 are related to a variety of mild to severe clinical
      symptoms, including mental retardation. The analysis of 9 intronic single
      nucleotide polymorphisms in 214 patients with autism spectrum disorder and 258
      controls revealed the association of 2 single nucleotide polymorphisms and 1
      haplotype with autism spectrum disorder (P < .05).

PMID- 22378670
TI  - Mortality risk after neonatal seizures in very preterm newborns.
AB  - We analyzed clinical and instrumental data of 403 consecutive newborns with
      gestational age from 24 to 32 weeks, admitted to the University-Hospital of Parma
      between January 2000 and December 2007, to evaluate the possible relationship
      between neonatal mortality and occurrence of neonatal seizures in very preterm
      newborns. Seventy-four subjects died during hospital stay. Seizures were present
      in 35 neonates, in whom the mortality rate was 37.1%. Multivariate analysis
      revealed that birth-weight <1000 g (odds ratio: 4.48; 95% confidence interval:
      1.47-13.68; P < .01), cardiopulmonary resuscitation (odds ratio: 5.35; 95%
      confidence interval: 1.19-23.98; P = .02), and moderately and severely abnormal
      cerebral ultrasound scan findings (odds ratio: 2.48; 95% confidence interval:
      1.02-6.05; P < .04; odds ratio: 9.56; 95% confidence interval: 3.45-26.51; P <
      .01, respectively) were related to the in-hospital mortality but not the presence
      of neonatal seizures. Our study suggests that neonatal seizures alone are not an
      independent risk factor for early death in very preterm newborns.

PMID- 22378671
TI  - Very early onset and severe complicated phenotype caused by a new spastic
      paraplegia 3A gene mutation.
AB  - Spastic paraplegia 3A is the second most common form of hereditary autosomal
      dominant spastic paraplegia. This form is mainly associated with an early age of
      onset and pure phenotype, although recently complicated forms were reported. We
      describe a patient carrying a new C>T P344S>CT mutation in exon 10 of the spastic
      paraplegia 3A gene with unusual, complicated, and extremely severe phenotype. At
      the last neurologic examination performed at 17 years of life, the patient
      disclosed spastic tetraparesis, sensorimotor axonal neuropathy, cognitive and
      cranial nerve impairment, mild pes cavus, and distal amyotrophy.

PMID- 22378672
TI  - Zellweger syndrome and associated brain malformations: report of a novel Peroxin1
      (PEX1) mutation in a Native American infant.
AB  - Zellweger syndrome (cerebrohepatorenal syndrome) is very rare and is the most
      severe form of peroxisomal biogenesis disorders. These can be caused by mutations
      in any of the currently known Peroxin genes and typically present in the neonatal
      period with multiorgan involvement. Patients usually do not survive beyond 1 year
      of age. This article reports a case of Zellweger syndrome in a male Native
      American infant confirmed by clinical findings, imaging studies, and biochemical
      analysis. Genetic studies show a novel mutation (c.3030G>T, p.
      Glutamine1010Histidine) altering the last nucleotide of exon 19 in the Peroxin1
      (PEX1) gene.

PMID- 22378673
TI  - Mitochondrial disease in 22q13 duplication syndrome.
AB  - Both copy number changes in the 22q13 region and mitochondrial disease have been
      associated with autism spectrum disorder. In this report, for the first time, a
      girl with autism spectrum disorder is described who exhibits both mitochondrial
      disease and a 22q13.1-33 duplication. This child demonstrated hypotonia,
      developmental delays, growth deficiency, microcephaly, dysmorphic facial
      features, and white matter abnormalities, consistent with previous cases of 22q13
      region duplication. The patient also demonstrated a unique pattern of electron
      transport chain abnormalities with marked decreases in complex II and II/III in
      fibroblasts and complex I/III and II/III in muscle tissue. The 22q13.1-33 region
      contains 6 genes associated with mitochondrial function. Thus, disruption of this
      chromosomal region could cause many of the clinical findings in this child
      through disruption of mitochondrial function. Therefore, a mitochondrial workup
      should be considered in individuals with copy number changes within the 22q13
      region, such as those with Phelan-McDermid syndrome.

PMID- 22378674
TI  - Hemophagocytic lymphohistiocytosis with isolated central nervous system
      reactivation and optic nerve involvement.
AB  - Hemophagocytic lymphohistiocytosis is a rare childhood disorder characterized by
      uncontrolled proliferation of benign lymphocytes and histiocytes in multiple
      organs. Neurological presentations of central nervous system involvement are
      highly variable. The authors present a case of familial hemophagocytic
      lymphohistiocytosis in an 8-month-old girl with isolated central nervous system
      reactivation and optic nerve involvement. She presented with fever and
      hepatosplenomegaly at 2 months of age. Genetic studies confirmed familial
      hemophagocytic lymphohistiocytosis. There were no clinical features of central
      nervous system involvement at presentation. While on maintenance chemotherapy
      awaiting bone marrow transplant, she presented with new-onset seizures. Magnetic
      resonance imaging of the brain revealed extensive areas of abnormal signal and a
      thickened and enhancing left optic nerve. Ocular manifestations of hemophagocytic
      lymphohistiocytosis have rarely been described. To the authors' knowledge, this
      is the first case report of magnetic resonance imaging findings of optic nerve
      involvement in a child with hemophagocytic lymphohistiocytosis.

PMID- 22378675
TI  - Niemann-pick disease type C: implications for sedation and anesthesia for
      diagnostic procedures.
AB  - Niemann-Pick disease type C, an autosomal recessive lysosomal storage disorder,
      can present with severe visceral and neurologic involvement and is associated
      with a significant decrease in life expectancy. As little is known about
      anesthetic considerations of this disease, we examined the perianesthetic course
      of patients with Niemann-Pick disease type C. Thirty-two patients with Niemann
      Pick disease type C, median age 6.9 years (1.8-33 years), underwent 64 general
      anesthetics for diagnostic procedures. Perianesthetic morbidity included need for
      tracheal reintubation, pneumonitis, hypothermia, and seizure. Therefore, Niemann
      Pick disease type C-associated neurologic and visceral involvement might have
      anesthetic implications that neurologists and pediatricians should be aware of
      and consider discussing with parents, guardians, and the patient's care team when
      procedures requiring anesthesia are planned. Furthermore, it is important for
      delivery of safe anesthesia that there is communication among care team members
      so that all involved understand the disease manifestation spectrum.

PMID- 22378676
TI  - Congenital thrombotic thrombocytopenic purpura associated with moyamoya syndrome
      in a 3-year-old girl: a case report.
AB  - A 3-year-old girl who presented with anemia, thrombocytopenia, and recurrent
      strokes is described. The cerebral angiography revealed moyamoya vasculopathy.
      Her younger brother also had anemia and thrombocytopenia but no neurologic
      abnormalities. Both children had severe deficiency of ADAMTS13 (A Disintegrin And
      Metalloprotease with Thrombospondin like domain activity) confirming the
      diagnosis of congenital thrombotic thrombocytopenic purpura. The children
      responded well to regular fresh-frozen plasma infusions. This report expands the
      spectrum of hematologic diseases associated with moyamoya syndrome. Unexplained
      thrombocytopenia, especially in the presence of neurologic symptoms, should
      prompt an evaluation for ADAMTS13deficiency. The diagnosis has significant
      implications not only for therapy but also for genetic counseling.

PMID- 22378677
TI  - Chiari 2 without spinal dysraphism: does it blow a hole in the pathogenesis?
AB  - Chiari malformation type 2 is characterized by hindbrain protrusion and a
      constellation of supratentorial malformations. Chiari malformation type 2 is
      thought to be causally related to myelomeningocele due to intrauterine
      cerebrospinal fluid overdrainage. This relationship is so strong that it has
      become a rule. A 14-year-old girl affected by mental retardation, spastic
      triparesis, and epilepsy is presented. Brain magnetic resonance imaging disclosed
      a severe Chiari malformation type 2, whereas spine magnetic resonance imaging was
      unremarkable. The authors discuss previous literature describing rare cases of
      Chiari malformation type 2 without open spinal dysraphism and the relevance of
      concomitant, sometimes overlooked, neuroimaging findings, underlying how
      exceptions might be hurdles but might also eventually strengthen the rules.

PMID- 22378678
TI  - Transmission of carbapenem-resistant pathogens in New York City hospitals:
      progress and frustration.
AB  - OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii
      and Pseudomonas aeruginosa are endemic in many medical centres. Because
      therapeutic options are limited, understanding the epidemiology and controlling
      the spread of these pathogens are of paramount importance. METHODS: Isolates of
      K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in
      New York City over a 3 month period in 2009, and analysed for the presence of
      genes encoding important carbapenemases. Comparisons were made with a similar
      study conducted in 2006. Demographic and infection control-related information
      from hospitals was collected. RESULTS: Overall, 29% of K. pneumoniae possessed
      the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P <
      0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to
      the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The
      decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the
      hospitals. In a subset analysis of nine hospitals, those with a decreasing
      prevalence of bla(KPC) had shorter average lengths of stay. CONCLUSIONS:
      Measurable improvement has occurred in reducing the spread of KPC-possessing K.
      pneumoniae, and reducing the average length of stay may augment infection control
      efforts. However, the problem of carbapenem-resistant A. baumannii and P.
      aeruginosa lingers. New approaches, including respiratory isolation and
      environmental cleaning, need to be examined to control the spread of A. baumannii
      and P. aeruginosa.

PMID- 22378679
TI  - New peptide deformylase inhibitors and cooperative interaction: a combination to
      improve antibacterial activity.
AB  - OBJECTIVES: Bacterial drug resistance is a worrying public health problem and
      there is an urgent need for research and development to provide new antibacterial
      molecules. Peptide deformylase (PDF) is now a well-described intracellular target
      selected for the design of a new antibiotic group, PDF inhibitors (PDFIs). The
      initial bacterial susceptibility to an inhibitor of a cytoplasmic target is
      directly associated with the diffusion of the compound through the membrane
      barrier of Gram-negative bacteria and with its cytosolic accumulation at the
      required concentration. METHODS: We have recently demonstrated that the activity
      of different PDFIs is strongly dependent on the accumulation of the active
      molecules by using permeabilizing agents, efflux inhibitors or efflux-mutated
      strains. In this work we assessed various combination protocols using different
      putative inhibitors (PDFIs, methionine aminopeptidase inhibitors etc.) to improve
      antibacterial activity against various resistant Gram-negative bacteria. RESULTS:
      The maximum effect was observed when combining actinonin with a dual inhibitor of
      methionine aminopeptidase and PDF, this molecule being also able to interact with
      the target while actinonin is bound to the PDF active site. CONCLUSIONS: Such a
      combination of inhibitors acting on two tightly associated metabolic steps
      results in a cooperative effect on bacterial cells and opens an original way to
      combat multidrug-resistant bacteria.

PMID- 22378680
TI  - Comparing neonatal and paediatric antibiotic prescribing between hospitals: a new
      algorithm to help international benchmarking.
AB  - OBJECTIVES: The WHO anatomical therapeutic chemical (ATC)/defined daily dose
      (DDD) methodology is a standardized method of comparing antimicrobial use. The
      ATC/DDD is defined as the average maintenance daily dose of a drug used in a 70
      kg adult, ignoring the considerable differences in body weight of neonates and
      children. The aim of this study was to develop a new standardized way of
      comparing rates of antimicrobial prescribing between European children's
      hospitals. METHODS: This pilot study at four European children's hospitals (in
      the UK, Greece and Italy) collected data including demographics, antibiotic use,
      dosing and indication in children and neonates over a 14 day period. RESULTS: A
      total of 1217 antibiotic prescriptions were issued with 47 different antibiotics
      used. Approximately half of all children and a third of all neonates received
      antibiotics, with wide variation between centres in the type and dose of
      antibiotic used. We propose a new pragmatic three-step algorithm. The first step
      includes a simple comparison of the proportion of hospitalized children on
      antibiotics by weight bands and the number of antimicrobials that account for 90%
      of total DDD drug usage (DU90%). The second step is a comparison of the dosing
      used (mg/kg/day). The third step is to compare overall drug exposure using
      DDD/100 bed days for standardized weight bands between centres. CONCLUSIONS: This
      novel method has the potential to be a useful tool to provide antibiotic use
      comparator data and requires validation in a large prospective point prevalence
      study.

PMID- 22378681
TI  - Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage
      strategy for HIV-1-infected patients on a failing antiretroviral regimen.
AB  - OBJECTIVES: To assess the efficacy and safety of dual-antiretroviral therapy
      containing a ritonavir-boosted protease inhibitor (PI/r) in treatment-experienced
      patients failing a current antiretroviral regimen. METHODS: Retrospective
      analysis of 60 consecutive HIV-1-infected patients who started a dual
      antiretroviral rescue regimen containing a PI/r, in three hospitals in Spain.
      Virological failure was defined as confirmed HIV RNA >50 copies/mL at treatment
      week 24 or later. The percentage of patients remaining free of therapeutic
      failure was estimated using the Kaplan-Meier method, by intent-to-treat analysis
      (missing, changes and virological failure = therapeutic failure). RESULTS: Median
      baseline characteristics of patients were: 13 years on antiretroviral therapy
      (four prior highly active antiretroviral therapy regimens and eight different
      drugs), 380 CD4 cells/mm(3) and HIV RNA 3.04 log(10) copies/mL. All patients had
      resistance mutations to at least two drug classes, although only 9.3% had
      specific mutations to darunavir. A darunavir-based regimen was started in 47
      (78.4%) patients, combined with etravirine (26.7%), tenofovir (26.7%) or
      raltegravir (25%). Three (5%) patients discontinued treatment due to side
      effects. At the end of follow-up, 86.7% of patients remained free of therapeutic
      failure; the percentages of patients with no therapeutic failure at treatment
      weeks 24, 48 and 96 were 96.6% (95% CI, 91.9-101.3); 90.1% (95% CI, 81.9-98.3)
      and 79.8% (95% CI, 66.1-93.5), respectively. CONCLUSIONS: Our results suggest
      that a dual-therapy rescue regimen including a PI/r is convenient, well tolerated
      and potent enough to achieve persistent viral suppression in selected pre-treated
      patients with low viral load and few PI resistance mutations.

PMID- 22378682
TI  - Fitness cost: a bacteriological explanation for the demise of the first
      international methicillin-resistant Staphylococcus aureus epidemic.
AB  - OBJECTIVES: Denmark and several other countries experienced the first epidemic of
      methicillin-resistant Staphylococcus aureus (MRSA) during the period 1965-75,
      which was caused by multiresistant isolates of phage complex 83A. In Denmark
      these MRSA isolates disappeared almost completely, being replaced by other phage
      types, predominantly only penicillin resistant. We investigated whether isolates
      of this epidemic were associated with a fitness cost, and we employed a
      mathematical model to ask whether these fitness costs could have led to the
      observed reduction in frequency. METHODS: Bacteraemia isolates of S. aureus from
      Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to
      phage complex 83A, clonal complex 8 based on spa type, ranging in time of
      isolation from 1957 to 1980 and with various antibiograms, including both
      methicillin-resistant and -susceptible isolates. The relative fitness of each
      isolate was determined in a growth competition assay with a reference isolate.
      RESULTS: Significant fitness costs of 2%-15% were determined for the MRSA
      isolates studied. There was a significant negative correlation between number of
      antibiotic resistances and relative fitness. Multiple regression analysis found
      significantly independent negative correlations between fitness and the presence
      of mecA or streptomycin resistance. Mathematical modelling confirmed that fitness
      costs of the magnitude carried by these isolates could result in the
      disappearance of MRSA prevalence during a time span similar to that seen in
      Denmark. CONCLUSIONS: We propose a significant fitness cost of resistance as the
      main bacteriological explanation for the disappearance of the multiresistant
      complex 83A MRSA in Denmark following a reduction in antibiotic usage.

PMID- 22378684
TI  - Gold-nanoparticle-embedded polydimethylsiloxane elastomers for highly sensitive
      Raman detection.
AB  - A simple, convenient, and efficient method for highly sensitive Raman detection
      is made by using a Au nanoparticle (AuNP)-embedded polydimethylsiloxane (PDMS)
      elastomer, referred to as AuNP-PDMS. When this AuNP-PDMS layer is applied to a
      surface, it can dramatically enhance the Raman signal of detected molecules.
      Moreover, it can be used for sensitive chemical imaging on solid substrates. As a
      proof of concept, patterned chemical images of p-aminothiophenol and methylene
      blue on a Ag substrate are obtained after this chemically patterned Ag substrate
      is covered by AuNP-PDMS.

PMID- 22378683
TI  - A murine model of Cryptococcus gattii meningoencephalitis.
AB  - OBJECTIVES: Meningoencephalitis caused by Cryptococcus gattii is associated with
      significant morbidity and the need for aggressive therapy, and often necessitates
      neurosurgical intervention. We adapted a previously described murine model of
      cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by
      C. gattii. METHODS: Mice were inoculated intracranially with either C. gattii
      (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii
      infecting inocula were compared with a fixed inoculum of C. neoformans, and
      differences were assessed by survival, brain tissue fungal burden, serum antigen
      titres and histopathological changes within brain tissue. For treatment,
      fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post
      inoculation. RESULTS: C. gattii was more virulent than C. neoformans, as evident
      by shorter median survival, earlier histopathological changes and higher serum
      antigen titres. However, no differences in fungal burden or dissemination to
      other organs were observed among the various groups. In treatment studies, both
      fluconazole and posaconazole improved the median survival of mice infected with
      either species. However, neither regimen improved the percentage of animals
      surviving to the predetermined study endpoint. CONCLUSIONS: These results
      demonstrate the virulence of C. gattii meningoencephalitis and the potential of
      this model for the assessment of new treatment strategies.

PMID- 22378685
TI  - Long-lasting enhancement of GABA(A)  receptor expression in newborn dentate
      granule cells after early-life febrile seizures.
AB  - Febrile seizures (FS) are the most common type of seizures in childhood and are
      suggested to play a role in the development of temporal lobe epilepsy (TLE).
      Animal studies demonstrated that experimental FS induce a long-lasting change in
      hippocampal excitability, resulting in enhanced seizure susceptibility.
      Hippocampal neurogenesis and altered ion channel expression have both been
      proposed as mechanisms underlying this decreased seizure threshold. The present
      study aimed to analyze whether dentate gyrus (DG) cells that were born after FS
      and matured for 8 weeks display an altered repertoire of ligand-gated ion
      channels. To this end, we applied an established model, in which FS are elicited
      in 10-day-old rat pups by hyperthermia (HT). Normothermia littermates served as
      controls. From postnatal day 11 (P11) to P16, rats were injected with
      bromodeoxyuridine (BrdU) to label dividing cells immediately following FS. At
      P66, we evaluated BrdU-labeled DG cells for coexpression with gamma-aminobutyric
      acid-type A receptors (GABA(A)Rs) and N-methyl-D-aspartate receptors (NMDARs). In
      control animals, 40% of BrdU-labeled cells coexpressed GABA(A)R beta2/3, whereas
      in rats that had experienced FS, 60% of BrdU-labeled cells also expressed
      GABA(A)R beta2/3. The number of BrdU-NMDAR NR2A/B coexpressing cells was in both
      groups about 80% of BrdU-labeled cells. The results demonstrate that
      developmental seizures cause a long-term increase in GABA(A)R beta2/3 expression
      in newborn DG cells. This may affect hippocampal physiology.

PMID- 22378686
TI  - A highly efficient and selective polysilsesquioxane sorbent for heavy metal
      removal.

PMID- 22378687
TI  - A young man with a sudden 'white out' of right hemithorax on chest radiograph.

PMID- 22378688
TI  - Value of routine bone marrow examination in pediatric acute myeloid leukemia
      (AML): a study of the Dutch Childhood Oncology Group (DCOG).
AB  - BACKGROUND: The outcome of the treatment of pediatric acute myeloid leukemia
      (AML) is still disappointing, due to relatively high treatment-related mortality
      and relapse rates (30-40%). Past treatment protocols have called for routine
      screening via bone marrow aspiration (BMA) after achievement of first complete
      remission (CR1) to detect relapse at an early stage. However, supporting evidence
      for this policy is lacking for non-FAB type-M3 patients. PROCEDURE: We therefore
      retrospectively studied the clinical relevance of routine BMA in an unselected
      cohort of all pediatric AML patients in the Netherlands. RESULTS: Of 440
      patients, data for 349 patients, of whom 148 suffered bone marrow relapse (BM
      relapse), could be analyzed. A total of 1,790 BMAs had been performed, 1,648
      (92%) routinely, and 142 (8%) on indication when a relapse was suspected. Forty
      routine BMAs showed BM-relapse (2% of all routine BMAs), while as many as 108
      (76%) hematological relapses were confirmed by BMA on indication (P < 0.001).
      Therefore, 1 in 41 routine BMAs, as opposed to 1 in 1.3 BMAs performed on
      indication, detected a BM-relapse. CONCLUSIONS: Routine BMA after CR1 did not
      significantly contribute to early detection of relapsed AML. These results
      suggest that BMA after achievement of CR1 should only be performed on indication
      or within a clinical research setting. Pediatr Blood Cancer 2012; 59: 1239-1244.
      (c) 2012 Wiley Periodicals, Inc.

PMID- 22378689
TI  - Copper-catalyzed C-H oxidation/cross-coupling of alpha-amino carbonyl compounds.
AB  - Keeping options open: the new and mild title reaction involving indoles
      selectively furnishes 1 and 2 with the aid of tert-butyl hydroperoxide (TBHP).
      The method represents the first example of a copper-catalyzed alpha arylation of
      alpha-amino carbonyl substrates leading to alpha-aryl alpha-imino and alpha-aryl
      alpha-oxo carbonyl compounds using a C-H oxidation strategy.

PMID- 22378690
TI  - Preparation of continuous gold nanowires by electrospinning of high-concentration
      aqueous dispersions of gold nanoparticles.
AB  - Gold nanowires are prepared by the electrospinning of highly concentrated aqueous
      dispersions of gold nanoparticles (AuNPs) in the presence of poly(vinyl alcohol)
      and subsequent annealing at higher temperatures. Continuous wires of sintered
      AuNPs are obtained as a result of this process. The Au wires are characterized by
      transmission electron microscopy, helium ion microscopy, optical microscopy, and
      X-ray diffractometry.

PMID- 22378691
TI  - Structural competition between halogen bonds and lone-pair...pi interactions in
      solution.
AB  - Structural competition between halogen bonds and lone-pair...pi interactions in
      solution is studied using (13)C NMR combined with density functional theory
      calculations. Among the halogen bonds considered, only the iodine bonds and a few
      bromine bonds are strong enough to compete successfully with the lone-pair...pi
      interactions.

PMID- 22378692
TI  - Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering.
AB  - Collapsin response mediator protein 1 (CRMP1) and CRMP2 have been known as
      mediators of extracellular guidance cues such as semaphorin 3A and contribute to
      cytoskeletal reorganization in the axonal pathfinding process. To date, how CRMP1
      and CRMP2 focally regulate axonal pathfinding in the growth cone has not been
      elucidated. To delineate the local functions of these CRMPs, we carried out
      microscale-chromophore-assisted light inactivation (micro-CALI), which enables
      investigation of localized molecular functions with highly spatial and temporal
      resolutions. Inactivation of either CRMP1 or CRMP2 in the neurite shaft led to
      arrested neurite outgrowth. Micro-CALI of CRMP2 in the central domain of the
      growth cones consistently arrested neurite outgrowth, whereas micro-CALI of CRMP1
      in the same region caused significant lamellipodial retraction, followed by
      retardation of neurite outgrowth. Focal inactivation of CRMP1 in its half region
      of the growth cone resulted in the growth cone turning away from the irradiated
      site. Conversely, focal inactivation of CRMP2 resulted in the growth cone turning
      toward the irradiated site. These findings suggest different functions for CRMP1
      and CRMP2 in growth cone behavior and neurite outgrowth.

PMID- 22378693
TI  - Uncharacterized 4,5-dihydroxy-2,3-pentanedione (DPD) molecules revealed through
      NMR spectroscopy: implications for a greater signaling diversity in bacterial
      species.

PMID- 22378695
TI  - Evaluating sex differences in medical device clinical trials: time for action.

PMID- 22378694
TI  - Oral health behavior and metabolic syndrome and its components in adults.
AB  - Inflammation has been strongly related to metabolic syndrome (MetS). Periodontal
      disease is the most common chronic infection in adults. We investigated a cross
      sectional (n = 925) and 3-year longitudinal (n = 685) relationship between the
      daily frequency of toothbrushing and MetS. In the cross-sectional analysis, the
      prevalence of MetS was 15.7%. After adjustment for potential confounding factors
      (including all lifestyle factors), the odds ratios (95% confidence interval [CI])
      of having MetS in those who brushed 2 times/day and >= 3 times/day were 0.71
      (0.48-1.05) and 0.47 (0.24-0.92), respectively, as compared with ratios in those
      with a toothbrushing frequency of <= 1 time/day. Increasing toothbrushing
      frequency tended to relate inversely to hypertriglyceridemia and high-sensitivity
      C-reactive protein. In the longitudinal analysis, 99 participants were newly
      diagnosed with MetS. The adjusted odds ratios (95% CI) of the MetS in
      participants who brushed 2 times/day and >= 3 times/day as compared with
      participants who brushed <= 1 time/day were 0.80 (0.49-1.31) and 0.43 (0.19
      0.97), respectively. The frequency of toothbrushing was related inversely only to
      hypertriglyceridemia, consistent with the cross-sectional analysis. This study
      found that more frequent toothbrushing is related to a lower prevalence and
      incidence of MetS. These results suggest that more frequent toothbrushing may
      contribute to the prevention of MetS due to the inflammation/triglyceride
      pathway.

PMID- 22378696
TI  - Levetiracetam for busulfan-induced seizure prophylaxis in children undergoing
      hematopoietic stem cell transplantation.
AB  - Anti-seizure prophylaxis is routinely utilized during busulfan administration for
      HSCT. We evaluated the feasibility and efficacy of levetiracetam in children
      undergoing HSCT. A total of 28 children and young adults received levetiracetam
      during HSCT and the outcomes and costs were compared to a historical, but similar
      cohort of 25 patients who had received fosphenytoin. Levetiracetam was well
      tolerated and was efficacious in preventing seizures. Cost of drug,
      administration, and monitoring were also similar among the two groups. Due to non
      induction of the hepatic cytochrome P450 enzymes, levetiracetam may lead to
      better dose assurance of busulfan in targeted dose regimens for HSCT.

PMID- 22378697
TI  - On the mechanisms of Ni-catalysed graphene chemical vapour deposition.

PMID- 22378698
TI  - Dynamic 3D patterning of biochemical cues by using photoinduced bioorthogonal
      reactions.

PMID- 22378699
TI  - Plasmonic-coupling-based sensing by the assembly and disassembly of
      dipycolylamine-tagged gold nanoparticles induced by complexing with cations and
      anions.
AB  - A surface-plasmon-coupling-mediated sensor system is developed based on Au
      nanoparticles tagged with a coordinative dipycolylamine and lipoyl-anchored
      naphthalimide derivative (AuNP@DPA). The AuNPs with tailored ligands exhibit
      distinct sensing activity via sequential assembly into nanoparticle aggregates
      induced by metal ion complexing, and disassembly in the presence of pyrophosphate
      (PPi) anions, which is accompanied by a swift, reversible color change due to a
      surface plasmon resonance coupling effect. It is found that divalent metal ions
      are more effective than mono- or tri-valent ions in the aggregate formation
      process, Mn(2+)-induced aggregates are more sensitive to the capture of PPi
      anions than other AuNP aggregates, and the disassembly upon anion complexation
      exhibits a highly selective response. The AuNP@DPA-based molecular recognition
      system also demonstrates a viable performance for the detection of total
      selective metal ions present in different types of water analytes.

PMID- 22378701
TI  - A cellular delivery system fabricated with autologous BMSCs and collagen scaffold
      enhances angiogenesis and perfusion in ischemic hind limb.
AB  - Although therapeutic cellular angiogenesis is effective for chronic ischemia, the
      optimal mode of cellular administration is still under exploration. This study
      aimed to develop a cellular delivery system to enhance the perfusion and
      angiogenesis in the ischemic hind limb. Collagen scaffold (CS) was prepared, and
      for morphology and toxicity analysis, bone marrow-derived mesenchymal stem cells
      (BMSCs) were isolated, expanded, filtrated, and seeded onto CS to construct BMSCs
      CS. The ischemic hind limbs of rabbit models were implanted with autologous BMSCs
      CS, CS, and autologous BMSCs; the untreated ischemic or normal animals were
      considered as the ischemic or normal control groups. Oxygen saturation parameters
      were regularly measured to determine the perfusion in the extremities.
      Histological examinations with hematoxylin and eosin immunostaining against von
      Willebrand factor and smooth muscle (SM) alpha-actin were performed for capillary
      and mature vessel evaluation. CS was a multiporous structure without
      cytotoxicity. At several intervals, the oxygen saturation ratio (OSR) in normal
      control was the highest. The OSRs in BMSCs-CS and CS were higher than that in
      BMSCs and ischemic control (p < 0.05); the OSR in BMSCs-CS group was higher than
      that in CS at 6 and 8 weeks (p < 0.05). The capillaries in BMSCs-CS and CS were
      higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The
      mature vessels in BMSCs-CS were higher than that in CS, BMSCs, and the ischemic
      or normal control (p < 0.05). The autologous cellular delivery system proved to
      be an effective approach for improving higher ischemic hind limb perfusion and
      angiogenesis as opposed to cellular therapy alone.

PMID- 22378700
TI  - Programming and reprogramming neuronal subtypes in the central nervous system.
AB  - Recent discoveries in nuclear reprogramming have challenged the dogma that the
      identity of terminally differentiated cells cannot be changed. The identification
      of molecular mechanisms that reprogram differentiated cells to a new identity
      carries profound implications for regenerative medicine across organ systems. The
      central nervous system (CNS) has historically been considered to be largely
      immutable. However, recent studies indicate that even the adult CNS is imparted
      with the potential to change under the appropriate stimuli. Here, we review
      current knowledge regarding the capability of distinct cells within the CNS to
      reprogram their identity and consider the role of developmental signals in
      directing these cell fate decisions. Finally, we discuss the progress and current
      challenges of using developmental signals to precisely direct the generation of
      individual neuronal subtypes in the postnatal CNS and in the dish.

PMID- 22378702
TI  - Planar cell polarity protein localization in the secretory ameloblasts of rat
      incisors.
AB  - The localization of the planar cell polarity proteins Vang12, frizzled-3, Vang11,
      and Celsr1 in the rat incisors was examined using immunocytochemistry. The
      results showed that Vang12 was localized at two regions of the Tomes' processes
      of inner enamel-secretory ameloblasts in rat incisors: a proximal and a distal
      region. In contrast, frizzled-3 was localized at adherens junctions of the
      proximal and distal areas of inner enamel- and outer enamel-secretory
      ameloblasts, where N-cadherin and beta-catenin were localized. frizzled-3 was
      also localized in differentiating inner enamel epithelial cells. Vang11 was
      localized sparsely in differentiating preameloblasts and extensively at the cell
      boundary of stratum intermedium. Celsr1 was not localized in ameloblasts but
      localized in odontoblasts extensively. These results suggest the involvement of
      planar cell polarity proteins in odontogenesis.

PMID- 22378703
TI  - Preparation and characterization of decellularized tendon slices for tendon
      tissue engineering.
AB  - To develop a naturally derived tendon tissue engineering scaffold with the
      preservation of the native ultrastructure, tensile strength, and biochemical
      composition of the tendon extracellular matrix (ECM), decellularized tendon
      slices (DTSs) were prepared using repetitive freeze/thaw of the intact Achilles
      tendons, frozen section, and nuclease treatment. The DTSs were characterized in
      the native ultrastructure, mechanical properties, biochemical composition, and
      cytocompatibility. Histological examination and DNA quantification analysis
      confirmed that cells were completely removed from tendon tissue by repetitive
      freeze/thaw in combination with nuclease treatment 12 h. The intrinsic
      ultrastructure of tendon tissue was well preserved based on scanning electron
      microscopy examination. The tensile strength of the DTSs was retained 85.62% of
      native tendon slice. More than 93% of proteoglycans (fibromodulin, biglycan) and
      growth factors (TGF-beta1, IGF-1, VEGF, and CTGF) inherent in tendon ECM were
      preserved in the DTSs according to ELISA analysis. Furthermore, the DTSs
      facilitated attachment and repopulation of NIH-3T3 fibroblasts in vitro. Overall,
      the DTSs are sheet scaffolds with a combination of elemental mechanical strength
      and tendon ECM bioactive factors that may have many potential applications in
      tendon tissue engineering.

PMID- 22378704
TI  - Watching single gold nanorods grow.
AB  - The consecutive evolution process of single gold nanorods is monitored using
      atomic force microscopy (AFM). The single-crystal gold nanorods investigated are
      grown directly on surfaces to which gold seed particles are covalently linked.
      The growth kinetics for single nanorods is derived from the 3D information
      recorded by AFM. A better understanding of the seed-mediated growth mechanism may
      ultimately lead to the direct growth of aligned nanorods on surfaces.

PMID- 22378706
TI  - Cyanosilylation of carbonyl compounds with trimethylsilyl cyanide catalyzed by an
      yttrium-pillared silicotungstate dimer.

PMID- 22378709
TI  - Biomimetic assembly of proteins into microcapsules on oil-in-water droplets with
      structural reinforcement via biomolecular-recognition-based cross-linking of
      surface peptides.
AB  - By mimicking the stabilization of bacterial membranes with S-layer proteins, a
      novel process to fabricate highly stable protein microcapsules is introduced. In
      this strategy, engineered collagen peptides with site-specific biotinylation are
      assembled into microcapsules on the oil-in-water droplets, and the resulting
      microcapsules are reinforced by biomolecular-recognition-based cross-linking with
      the protein. Furthermore the microcapsules are shown to be versatile scaffolds
      for developing functionalized hierarchical colloidosomes for important
      biotechnological applications.

PMID- 22378710
TI  - StochSens--Matlab package for sensitivity analysis of stochastic chemical
      systems.
AB  - MOTIVATION: The growing interest in the role of stochasticity in biochemical
      systems drives the demand for tools to analyse stochastic dynamical models of
      chemical reactions. One powerful tool to elucidate performance of dynamical
      systems is sensitivity analysis. Traditionally, however, the concept of
      sensitivity has mainly been applied to deterministic systems, and the difficulty
      to generalize these concepts for stochastic systems results from necessity of
      extensive Monte Carlo simulations. RESULTS: Here we present a Matlab package,
      StochSens, that implements sensitivity analysis for stochastic chemical systems
      using the concept of the Fisher Information Matrix (FIM). It uses the linear
      noise approximation to represent the FIM in terms of solutions of ordinary
      differential equations. This is the first computational tool that allows for
      quick computation of the Information Matrix for stochastic systems without the
      need for Monte Carlo simulations. AVAILABILITY:
      http://www.theosysbio.bio.ic.ac.uk/resources/stns SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 22378711
TI  - Grandfather Involvement and aging men's mental health.
AB  - The mental health of aging men is an understudied social issue. Although it is
      widely accepted that meaningful family relationships are associated with fewer
      depressive symptoms and greater positive affect, scholars have largely overlooked
      relationships between grandfathers and grandchildren as being beneficial to men's
      mental health. This study investigates the differences in the depressive symptoms
      and positive affect of 351 grandfathers. Using a cluster analytic technique,
      participants were categorized as involved, passive, and disengaged based on their
      frequency of contact, level of commitment, and participation in activities with
      grandchildren. Comparative analyses indicate that involved grandfathers had fewer
      depressive symptoms than disengaged grandfathers. Involved grandfathers had
      significantly higher scores on positive affect than disengaged grandfathers, and
      passive grandfathers had significantly higher scores on positive affect than
      disengaged grandfathers. This study provides evidence that grandfather-grandchild
      relationships influence aging men's mental health. Implications for practitioners
      working with aging men are discussed.

PMID- 22378712
TI  - Understanding men's body image in the context of their romantic relationships.
AB  - This study examined men's body image in the context of their romantic
      relationships. One hundred and four heterosexual romantic couples (N = 208
      participants) completed measures assessing men's body image, perceptions of men's
      weight change, relationship length, and sexual intimacy. Men's height and weight
      were also measured. Results indicate that men were more likely to be satisfied
      with their bodies when they perceived their partners to be, when their partners
      actually were satisfied with their bodies, and when they perceived themselves to
      have gained relatively little weight throughout the duration of their
      relationships. Analyses also revealed that men expressed greater body
      satisfaction when there was a relatively high degree of sexual intimacy in the
      relationship. Findings are discussed in terms of their contributions to
      researchers' and practitioners' understanding of men's body satisfaction.

PMID- 22378713
TI  - Total synthesis of the bacterial RNA polymerase inhibitor ripostatin B.
AB  - A modular and highly stereoselective synthesis of the title compound was
      developed. Key steps in the assembly of the carbon framework of ripostatin B were
      a stereoselective Paterson aldol reaction and a high-yielding ring-closing
      metathesis mediated by Grubbs first generation catalyst. The C15 hydroxy group
      was established through Tishchenko-Evans reduction in excellent yield and
      selectivity.

PMID- 22378714
TI  - Patient experiences of transitioning from hospital to home: an ethnographic
      quality improvement project.
AB  - BACKGROUND: Little is known about patient perspectives of the transition from
      hospital to home. OBJECTIVE: To develop a richly detailed, patient-centered view
      of patient and caregiver needs in the hospital-to-home transition. DESIGN: An
      ethnographic approach including participant observation and in-depth, semi
      structured video recorded interviews. SETTING: Kaiser Permanente's Southern
      California, Colorado, and Hawaii regions. PATIENTS: Twenty-four adult inpatients
      hospitalized for a range of acute and chronic conditions and characterized by
      variety in diagnoses, illness severity, planned or unplanned hospitalization,
      age, and ability to self manage. RESULTS: During the hospital-to-home transition,
      patients and caregivers expressed or demonstrated experiences in 6 domains: 1)
      translating knowledge into safe, health-promoting actions at home; 2) inclusion
      of caregivers at every step of the transition process; 3) having readily
      available problem-solving resources; 4) feeling connected to and trusting
      providers; 5) transitioning from illness-defined experience to "normal" life; and
      6) anticipating needs after discharge and making arrangements to meet them. The
      work of transitioning occurs for patients and caregivers in the hours and days
      after they return home and is fraught with challenges. CONCLUSIONS: Reducing
      readmissions will remain challenging without a broadened understanding of the
      types of support and coaching patients need after discharge. We are piloting
      strategies such as risk stratification and tailoring of care, a specialized phone
      number for recently discharged patients, standardized same-day discharge
      summaries to primary care providers, medication reconciliation, follow-up phone
      calls, and scheduling appointments before discharge.

PMID- 22378715
TI  - Development of a preliminary US power Doppler composite score for monitoring
      treatment in PsA.
AB  - OBJECTIVE: To develop a preliminary power Doppler (PD) US composite score for
      global assessment of PsA patients. METHODS: Sixteen PsA patients receiving anti
      TNF-alpha therapy were enrolled. All patients were involved in multiple psoriatic
      targets, including joints, tendon, enthesis, skin and nail. The target with the
      highest PD signal, one for each target area, was selected to be scanned at
      baseline and at follow-up visit 8 weeks after. For each target, PD was graded
      according to semi-quantitative scoring systems. Inter- and intra-observer
      reliability and feasibility was also investigated. The new PD composite score for
      PsA was called Five Targets PD for Psoriatic Disease (5TPD). RESULTS: Sixty
      targets (16 joints, 9 tendons, 11 enthesis, 16 psoriatic plaques and 8 psoriatic
      onychopathies) were assessed. A significant improvement of the clinical scores
      was found at follow-up with respect to the baseline: HAQ modified for SpA (HAQ-S)
      (P = 0.0001); Psoriasis Area and Severity Index (P = 0.0001) and Nail Psoriasis
      Severity Index (P = 0.35). The 5TPD showed a significant change between baseline
      and follow-up (P = 0.0001). There was no significant correlation between HAQ-S
      and 5TPD findings. The inter- and intra-observer kappa-values varied from good to
      excellent at baseline and follow-up. The time spent on baseline US examinations
      was mean (s.d.) 10.5 (2.0) min and no more than 7 min for follow-up assessment.
      CONCLUSION: The present study provides a new working hypothesis that the
      sonographic core set may be useful to construct a PDUS composite score for the
      assessment of PsA. The 5TPD formula provides a feasible and reliable approach for
      multi-target monitoring of psoriatic disease.

PMID- 22378716
TI  - Treatment decisions and related costs differ significantly depending on the
      choice of a disease activity index in RA, according to 1987 and 2010
      classification criteria.
AB  - OBJECTIVE: To evaluate the therapeutic and economic consequences of various
      disease activity indices (DAIs) in RA according to 1987 and 2010 criteria.
      METHODS: Data on disease activity states from all sustained visits were assessed
      from all patients who participate in the treatment in the Rotterdam Early
      Arthritis Cohort (tREACH) study, a stratified randomized trial to evaluate
      different treatment strategies in patients with a symptom duration of <1 year.
      Frequencies of treatment adaptations, based upon exclusive thresholds of various
      DAIs, were visualized in reclassification tables. The Stuart-Maxwell test was
      applied to analyse any significant differences between treatment decisions
      according to the different DAIs. Simulated annual median medication costs were
      estimated using the tREACH medication protocol with standard national costs.
      RESULTS: DAIs perform similar in RA according to 1987 and 2010 criteria. A total
      of 1104 DASs per DAI were available from 296 patients. DAIs differ significantly,
      compared with DASs, in classifying a patient's disease state. Consequently,
      treatment intensifications occur more frequently with SDAI, CDAI and DAS-28
      usage, compared with DAS. Tapering treatment occurs less frequently with SDAI and
      CDAI and more frequently with DAS-28 usage. Simulated annual median medication
      costs are significantly higher if DAS-28, SDAI and CDAI are used compared with
      DAS usage. CONCLUSION: Usage of various DAIs in a single patient leads to
      inconsistent disease state categorizations. Consequently, these inconsistencies
      significantly influence therapeutic decisions and accompanying costs. As DAI
      usage is imperative to uphold current European League Against Rheumatology
      (EULAR) treatment recommendations, physicians should consider these therapeutic
      and economic consequences before choosing a particular DAI.

PMID- 22378717
TI  - A systematic literature review of US definitions, scoring systems and validity
      according to the OMERACT filter for tendon lesion in RA and other inflammatory
      joint diseases.
AB  - OBJECTIVE: To present the published data concerning the US assessment of tendon
      lesions as well as the US metric properties investigated in inflammatory
      arthritis. METHODS: A systematic literature search of PubMed, Embase and the
      Cochrane Library was performed. Selection criteria were original articles in the
      English language reporting US, Doppler, tenosynovitis and other tendon lesions in
      patients with RA and other inflammatory arthritis. Data extraction focused on the
      definition and quantification of US-detected tenosynovitis and other tendon
      abnormalities and the metric properties of US according to the OMERACT filter for
      evaluating the above tendon lesions. RESULTS: Thirty-three of 192 identified
      articles were included in the review. Most articles were case series (42%) or
      case-control (33%) studies describing hand and/or foot tenosynovitis in RA
      patients. The majority of older articles used only B-mode, whereas the most
      recent studies have incorporated Doppler mode. Definition of tenosynovitis or
      other tendon lesion was provided in 70% of the evaluated studies. Most of the
      studies (61%) used a binary score for evaluating tendon abnormalities. Concerning
      the OMERACT filter, 24 (73%) articles dealt with construct validity. The
      comparator most commonly used was clinical assessment and MRI. There were few
      studies assessing criterion validity. Some studies evaluated reliability (36%),
      responsiveness (21%) and feasibility (12%). CONCLUSION: US seems a promising tool
      for evaluating inflammatory tendon lesions. However, further validation is
      necessary for implementation in clinical practice and trials.

PMID- 22378718
TI  - The diagnostic utility of anti-melanoma differentiation-associated gene 5
      antibody testing for predicting the prognosis of Japanese patients with DM.
AB  - OBJECTIVE: Interstitial lung disease (ILD), especially rapidly progressive ILD
      (RPILD), is a major poor prognostic factor in patients with DM. We investigated
      the association of anti-melanoma differentiation-associated gene 5 (MDA5)
      antibody (Ab) with clinical characteristics and mortality in Japanese patients
      with DM. METHODS: Seventy-nine DM patients, comprising 58 classic DM and 21
      clinically amyopathic DM (CADM) patients, were enrolled. Serum Abs were screened
      by immunoprecipitation assays, and an immunosorbent assay (ELISA) was used for
      MDA5. The relationships of clinical characteristics and mortality with each Ab
      were investigated. RESULTS: Anti-MDA5 Ab was detected in 17 patients. Anti
      clinically amyopathic DM 140  kDa polypeptide Abs (anti-CADM-140 Abs) were found
      in 16 of the 17 anti-MDA5 Ab(+) patients. Skin ulcers, palmar papules, CADM,
      RPILD and mediastinal emphysema were widely distributed in anti-MDA5 Ab(+)
      patients. Mortality at 6 months as well as 5 years was also significantly higher
      in anti-MDA5 Ab(+) patients than in anti-MDA5 Ab(-) patients. In a multivariable
      Cox regression analysis, mortality was independently associated with anti-MDA5 Ab
      (relative hazard 6.33; 95% CI 1.43, 28.0). All of the deaths in anti-MDA5 Ab(+)
      patients were attributed to respiratory failure of RPILD; however, RPILD did not
      worsen in any of the anti-MDA5 Ab(+) patients who survived the first 6 months.
      CONCLUSION: The presence of anti-MDA5 Ab identifies the characteristic skin,
      musculoskeletal, pulmonary and prognostic features in patients with DM. In
      addition, anti-MDA5 Ab seems to predict a group of patients with CADM-complicated
      fatal RPILD.

PMID- 22378719
TI  - Whole-body MRI in Erdheim-Chester disease.

PMID- 22378720
TI  - Control of epoxy creep using graphene.
AB  - The creep behavior of epoxy-graphene platelet (GPL) nanocomposites with different
      weight fractions of filler is investigated by macroscopic testing and
      nanoindentation. No difference is observed at low stress and ambient temperature
      between neat epoxy and nanocomposites. At elevated stress and temperature the
      nanocomposite with the optimal weight fraction, 0.1 wt% GPLs, creeps
      significantly less than the unfilled polymer. This indicates that thermally
      activated processes controlling the creep rate are in part inhibited by the
      presence of GPLs. The phenomenon is qualitatively similar at the macroscale and
      in nanoindentation tests. The results are compared with the creep of epoxy-single
      walled (SWNT) and multi-walled carbon nanotube (MWNT) composites and it is
      observed that creep in both these systems is similar to that in pure epoxy, that
      is, faster than creep in the epoxy-GPL system considered in this work.

PMID- 22378723
TI  - "Out of sight, out of mind": housestaff perceptions of quality-limiting factors
      in discharge care at teaching hospitals.
AB  - BACKGROUND: Improving hospital discharge has become a national priority for
      teaching hospitals, yet little is known about physician perspectives on factors
      limiting the quality of discharge care. OBJECTIVES: To describe the discharge
      process from the perspective of housestaff physicians, and to generate hypotheses
      about quality-limiting factors and key strategies for improvement. METHODS:
      Qualitative study with in-depth, in-person interviews with a diverse sample of 29
      internal medicine housestaff, in 2010-2011, at 2 separate internal medicine
      training programs, including 7 different hospitals. We used the constant
      comparative method of qualitative analysis to explore the experiences and
      perceptions of factors affecting the quality of discharge care. RESULTS: We
      identified 5 unifying themes describing factors perceived to limit the quality of
      discharge care: (1) competing priorities in the discharge process; (2) inadequate
      coordination within multidisciplinary discharge teams; (3) lack of
      standardization in discharge procedures; (4) poor patient and family
      communication; and (5) lack of postdischarge feedback and clinical
      responsibility. CONCLUSIONS: Quality-limiting factors described by housestaff
      identified key processes for intervention. Establishment of clear standards for
      discharge procedures, including interdisciplinary teamwork, patient
      communication, and postdischarge continuity of care, may improve the quality of
      discharge care by housestaff at teaching hospitals.

PMID- 22378724
TI  - Impact of prenatal multiple micronutrients on survival and growth during infancy:
      a randomized controlled trial.
AB  - BACKGROUND: Although prenatal multiple micronutrients can improve fetal growth,
      their benefit on postnatal health remains uncertain. OBJECTIVE: We assessed the
      effect of the UNICEF/WHO/United Nations University multiple micronutrient
      supplement for pregnant and lactating women (UNIMMAP) compared with the usual
      iron and folic acid supplement (IFA) on survival, growth, and morbidity during
      infancy. DESIGN: In a double-blind, randomized trial, we followed 1294 singleton
      newborns whose mothers had prenatally received either the UNIMMAP or IFA. We
      assessed monthly anthropometric measures and health variables up to age 12 mo.
      Children were assessed again at a mean age of 30 mo. Mixed-effects models
      accounted for repeated measurements. RESULTS: The UNIMMAP resulted in a 27% (HR:
      0.73; 95% CI: 0.60, 0.87; P = 0.002) reduction in the rate of stunting in 15,261
      infant-months with a higher length-for-age z score of 0.13 (95% CI: 0.02, 0.24; P
      = 0.02) over the whole observation period. However, by age 30 mo, this difference
      was not observed. An effect of the UNIMMAP on weight-for-length (P-interaction =
      0.004) and head circumference-for-age (P-interaction = 0.03) became apparent by
      the end of the first year of life. By the age of 30 mo, children from the UNIMMAP
      group had a higher weight-for-height z score of 0.20 (95% CI: 0.06, 0.34; P =
      0.004). No difference in mortality or morbidity was identified in groups, except
      a 14% reduction in reported episodes of fever (95% CI: 1%, 28%; P = 0.04).
      CONCLUSIONS: Improved linear fetal growth with continuation into early life and
      enhanced postnatal growth were 2 mechanisms that mediated the effect of the
      prenatal UNIMMAP on infant nutritional status. Additional follow-up to assess
      long-term effects is warranted.

PMID- 22378725
TI  - Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the
      activation of brown adipose tissue in humans.
AB  - BACKGROUND: Capsinoids-nonpungent capsaicin analogs-are known to activate brown
      adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in
      small rodents. BAT activity can be assessed by [18F]fluorodeoxyglucose-positron
      emission tomography (FDG-PET) in humans. OBJECTIVES: The aims of the current
      study were to examine the acute effects of capsinoid ingestion on EE and to
      analyze its relation to BAT activity in humans. DESIGN: Eighteen healthy men aged
      20-32 y underwent FDG-PET after 2 h of cold exposure (19 degrees C) while wearing
      light clothing. Whole-body EE and skin temperature, after oral ingestion of
      capsinoids (9 mg), were measured for 2 h under warm conditions (27 degrees C) in
      a single-blind, randomized, placebo-controlled, crossover design. RESULTS: When
      exposed to cold, 10 subjects showed marked FDG uptake into adipose tissue of the
      supraclavicular and paraspinal regions (BAT-positive group), whereas the
      remaining 8 subjects (BAT-negative group) showed no detectable uptake. Under warm
      conditions (27 degrees C), the mean (+/-SEM) resting EE was 6114 +/- 226 kJ/d in
      the BAT-positive group and 6307 +/- 156 kJ/d in the BAT-negative group (NS). EE
      increased by 15.2 +/- 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 +/-
      3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P < 0.01).
      Placebo ingestion produced no significant change in either group. Neither
      capsinoids nor placebo changed the skin temperature in various regions, including
      regions close to BAT deposits. CONCLUSION: Capsinoid ingestion increases EE
      through the activation of BAT in humans. This trial was registered at
      http://www.umin.ac.jp/ctr/ as UMIN 000006073.

PMID- 22378727
TI  - Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol
      supplementation in phytosterolemia heterozygotes and control individuals.
AB  - BACKGROUND: Plant sterol (PS) supplementation is increasingly accepted as a
      dietary strategy to lower plasma cholesterol concentrations. However, information
      is scarce about the effect of increased PS intake in potentially vulnerable
      groups, such as phytosterolemia heterozygotes (HET). OBJECTIVE: This study
      assessed the responsiveness of circulating PS and lipid concentrations and
      cholesterol kinetics (absorption and synthesis) to daily PS supplementation in
      HET (ABCG8 S107X mutation) compared with a healthy control cohort. DESIGN: A
      double-blind, randomized, crossover, placebo-controlled study was conducted in 10
      HET and 15 control subjects. The participants had a mean (+/-SEM) age of 34 +/- 2
      y and a BMI (in kg/m2) of 29.9 +/- 1.1 and consumed ~1.6 g PS or placebo capsules
      daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by
      using [13C]cholesterol and deuterium oxide, respectively. RESULTS: Plasma LDL
      cholesterol concentrations decreased (P = 0.006) in both groups after PS
      supplementation (HET: 2.73 +/- 0.19 mmol/L; control: 3.11 +/- 0.19 mmol/L)
      compared with placebo (HET: 3.12 +/- 0.20 mmol/L; control: 3.50 +/- 0.21 mmol/L),
      whereas PS concentrations (campesterol+beta-sitosterol) increased (P = 0.03) in
      both groups after PS supplementation (HET: 39.72 +/- 6.05 MUmol/L; control: 24.03
      +/- 1.65 MUmol/L) compared with placebo (HET: 27.32 +/- 3.80 MUmol/L; control:
      21.12 +/- 2.05 MUmol/L). Cholesterol absorption efficiency decreased (P = 0.010)
      by ~22% and ~17% and synthesis rates increased (P = 0.040) by ~20% and ~24% in
      the HET and control groups, respectively, in response to PS consumption compared
      with placebo. CONCLUSION: These data suggest that heterozygosity for the ABCG8
      S107X mutation does not influence the action of dietary PS on circulating
      cholesterol concentrations but may affect sterol absorption.

PMID- 22378728
TI  - Occupational burnout, eating behavior, and weight among working women.
AB  - BACKGROUND: Eating behavior affects weight and thus the development of obesity.
      Studies on the effect of occupational burnout (exhaustive fatigue, cynicism, and
      lost occupational self-respect caused by chronic work stress) on eating behavior
      are lacking. OBJECTIVE: The objective was to investigate associations between
      occupational burnout, eating behavior, and weight among working women. DESIGN: A
      total of 230 working women participated in a randomized controlled intervention
      trial (Nuadu) that aimed at changing the health behaviors of those with health
      risks. We assessed eating behavior using the Three-Factor Eating Behavior
      Questionnaire 18 and burnout using the Bergen Burnout Indicator 15 at both
      baseline and 12 mo. Body weight and percentage body fat were also measured at
      baseline and at 12 mo. The intervention and control groups were combined and
      divided by burnout and weight-change variables. RESULTS: Women experiencing
      burnout at baseline had significantly higher scores in emotional eating (EE; P =
      0.002) and uncontrolled eating (UE; P = 0.001) than did those without burnout. A
      significant difference was found between the change in UE from baseline to 12 mo
      in those with and without burnout (P = 0.05). UE decreased significantly among
      those without burnout at baseline (P < 0.001). CONCLUSIONS: Those experiencing
      burnout may be more vulnerable to EE and UE and have a hindered ability to make
      changes in their eating behavior. We recommend that burnout should be treated
      first and that burnout and eating behavior should be evaluated in obesity
      treatment.

PMID- 22378726
TI  - Experimental research on the relation between food price changes and food
      purchasing patterns: a targeted review.
AB  - One way in which to modify food purchases is to change prices through tax policy,
      subsidy policy, or both. We reviewed the growing body of experimental research
      conducted in the laboratory and in the field that investigates the following: the
      extent to which price changes influence purchases of targeted and nontargeted
      foods, total energy, or macronutrients purchased; the interaction of price
      changes with adjunctive interventions; and moderators of sensitivity to price
      changes. After a brief overview of economic principles and observational research
      that addresses these issues, we present a targeted review of experimental
      research. Experimental research suggests that price changes modify purchases of
      targeted foods, but research on the overall nutritional quality of purchases is
      mixed because of substitution effects. There is mixed support for combining price
      changes with adjunctive interventions, and there are no replicated findings on
      moderators to price sensitivity in experiments. Additional focused research is
      needed to better inform food policy development with the aim of improving eating
      behavior and preventing obesity.

PMID- 22378729
TI  - Dietary patterns matter: diet beverages and cardiometabolic risks in the
      longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study.
AB  - BACKGROUND: Although diet beverages are typically consumed to promote weight
      control, positive associations with increased cardiometabolic risk have been
      reported. OBJECTIVE: The objective was to examine the joint and independent
      association between dietary pattern and diet beverage consumption with 20-y
      cardiometabolic risk. DESIGN: We analyzed a prospective 20-y cohort of young
      adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
      With the use of cluster analysis, we identified 2 baseline (year 0) dietary
      patterns [Prudent (higher intakes of fruit, whole grains, milk, and nuts and
      seeds; n = 1778) and Western (higher intakes of fast food, meat and poultry,
      pizza, and snacks; n = 2383)] and examined the interaction with diet beverage
      consumption (Consumers compared with Nonconsumers) by using proportional hazards
      regression models. RESULTS: Among Consumers, 66% were classified as having a
      Prudent diet. In fully adjusted models, being a Nonconsumer with a Prudent diet
      was independently associated with a lower risk of the metabolic syndrome through
      year 20. Lower risk in the Prudent than in the Western dietary pattern was
      maintained after stratification by diet beverage consumption: Prudent
      Nonconsumers had the lowest risk of high waist circumference (HR: 0.78; 95% CI:
      0.62, 0.97), high triglycerides (HR: 0.72; 95% CI: 0.56, 0.93), and the metabolic
      syndrome (HR: 0.64; 95% CI: 0.50, 0.82) compared with Western Consumers.
      CONCLUSIONS: Our results suggest that both overall dietary pattern and diet
      beverage consumption are important, to various degrees, for different metabolic
      outcomes. This covariation and interaction may partially explain differences in
      the relation between diet beverage consumption and cardiometabolic health
      observed in previous studies.

PMID- 22378730
TI  - Associations of prenatal metabolic abnormalities with insulin and adiponectin
      concentrations in human milk.
AB  - BACKGROUND: Emerging evidence indicates that metabolic hormones are present in
      human milk, but, to our knowledge, no studies have investigated the impact of
      maternal metabolic status assessed during pregnancy on insulin and adiponectin
      concentrations in milk. OBJECTIVES: We aimed to investigate the associations of
      prenatal metabolic abnormalities with insulin and adiponectin in human milk and
      to compare the concentrations of these hormones in early and mature milk. DESIGN:
      Pregnant women aged >=20 y with intention to breastfeed and without preexisting
      type 1 or 2 diabetes were recruited. Participants (n = 170) underwent a 3-h oral
      glucose-tolerance test at 30 wk (95% CI: 25, 33 wk) gestation and donated early
      (the first week postpartum) and mature (3 mo postpartum) milk. RESULTS:
      Adiponectin and insulin concentrations in early milk were higher than those in
      mature milk (both P < 0.0001). Prenatal metabolic abnormalities, including higher
      pregravid BMI (beta +/- SEE: 0.053 +/- 0.014; P = 0.0003) and gravid
      hyperglycemia (0.218 +/- 0.087; P = 0.01), insulin resistance (0.255 +/- 0.047; P
      < 0.0001), lower insulin sensitivity (-0.521 +/- 0.108; P < 0.0001), and higher
      serum adiponectin (0.116 +/- 0.029; P < 0.0001), were associated with higher
      insulin in mature milk after covariate adjustment. Prenatal metabolic measures
      were not associated with milk adiponectin, but obstetrical measures that included
      nulliparity (0.171 +/- 0.058; P = 0.004), longer duration of gestation (0.546 +/-
      0.146; P = 0.0002), and unscheduled cesarean delivery (0.387 +/- 0.162; P = 0.02)
      were associated with higher adiponectin in early milk after covariate adjustment,
      including the time elapsed from delivery to milk collection. CONCLUSION: Maternal
      prenatal metabolic abnormalities are associated with high insulin concentrations
      in mature milk, whereas only obstetrical variables are associated with
      adiponectin concentrations in early milk.

PMID- 22378731
TI  - Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs.
AB  - BACKGROUND: Leukotrienes are proinflammatory molecules derived from dietary PUFAs
      and have been associated with cardiovascular disease (CVD). We previously
      reported that an A->G variant (rs12746200) of the cytosolic phospholipase A2
      group IVA gene (PLA2G4A), which encodes the enzyme that liberates PUFAs from
      cellular membranes for leukotriene synthesis, decreases the risk of CVD.
      OBJECTIVE: We sought to replicate these initial observations with a more
      clinically relevant phenotype, such as myocardial infarction (MI), and to
      determine whether dietary PUFAs mediate this association. DESIGN: In a Costa
      Rican case-control data set (n = 3971), rs12746200 was genotyped and was tested
      for an association with MI. Functional experiments were carried out to determine
      whether rs12746200 led to differences in mRNA expression. RESULTS: Risk of MI was
      significantly lower in AG/GG subjects than in AA homozygotes (OR: 0.86; 95% CI:
      0.75, 0.99; P = 0.040). The reduced risk of MI was observed primarily in AG/GG
      subjects who were above the median for intake of dietary omega-6 (n-6) PUFAs (OR:
      0.71; 95% CI: 0.59, 0.87; P-interaction = 0.005). A similar analysis with dietary
      omega-3 (n-3) PUFAs did not show a statistically significant nutrigenetic
      association (P-interaction = 0.23). Functional analysis in human aortic
      endothelial cells showed that the carriers of the G allele had significantly
      lower PLA2G4A gene expression (P = 0.014), consistent with the atheroprotective
      association of this variant. CONCLUSION: These results replicate the association
      of rs12746200 with CVD phenotypes and provide evidence that the protective
      association of this functional PLA2G4A variant is mediated by dietary PUFAs.

PMID- 22378732
TI  - The concept of "critical nutrient density" in complementary feeding: the demands
      on the "family foods" for the nutrient adequacy of young Guatemalan children with
      continued breastfeeding.
AB  - BACKGROUND: The WHO recommends the introduction of nutritionally adequate, safe,
      and appropriate complementary foods at 6 mo of age, with continued breastfeeding
      up to 2 y and beyond. Suggested strategies to support continued breastfeeding
      often postulate optimal use of customary "family foods" and adequate amounts of
      indigenous foodstuffs and local foods. OBJECTIVE: The objective was to determine
      the nutrient adequacy of the diet of Guatemalan children aged 6-24 mo receiving
      continued breastfeeding and "family foods" rather than specially formulated "baby
      foods" as complementary foods. DESIGN: "Critical nutrient densities" for
      complementary foods were determined by using specific energy and protein
      requirements, assuming children to be in the 50th or 15th weight percentile of
      the 2006 WHO standards. Nutrient requirements for the total diet were determined
      by using the recommended nutrient intakes. Breast milk was assumed to provide 75%
      of total energy between 7 and 9 mo, 50% between 10 and 12 mo, and 40% between 13
      and 24 mo. Gaps between computed critical nutrient densities and the best
      scenario Guatemalan adult's diet, as a proxy for family foods, were examined.
      RESULTS: Energy complementation with these diets provided adequate nutrient
      density for protein, thiamine, riboflavin, and vitamins B-6, B-12, and C but not
      vitamin A, niacin, and folate in some groups. Major gaps for calcium, iron, and
      zinc were ubiquitous. CONCLUSIONS: The critical nutrient density concept is
      useful to evaluate the nutrient adequacy of the young child's diet. Multiple
      micronutrients are likely to be limited in the diets of Guatemalan young children
      with continued breastfeeding and family foods.

PMID- 22378733
TI  - Intake of dietary procyanidins does not contribute to the pool of circulating
      flavanols in humans.
AB  - BACKGROUND: Accumulating data show a causal role for flavanols in the mediation
      of cardiovascular benefits associated with the consumption of flavanol- and
      procyanidin-containing foods. Evidence for a direct causal role for procyanidins
      in this context is far less profound due to the poor absorption of procyanidins.
      However, it has been proposed that procyanidins may break down in the
      gastrointestinal tract, resulting in monomeric flavanols, which contribute to the
      systemic flavanol pool. Verification or rejection of this supposition could
      significantly affect the interpretation of epidemiologic and dietary intervention
      data and the design of food-content databases. OBJECTIVE: We assessed the
      respective contribution of flavanols and procyanidins to the systemic pool of
      flavanols and 5-(3,4-dihydroxyphenyl)-gamma-valerolactone (gamma-VL) in humans.
      DESIGN: Test drinks that contained only flavanols (D1), procyanidins with a
      degree of polymerization that ranged from 2 to 10 (D2-10), or flavanols and
      procyanidins with a degree of polymerization that ranged from 2 to 10 (D1-10)
      were consumed by subjects (n = 12) according to a randomized, double-masked,
      crossover design. Plasma and urine samples were collected postprandially and
      analyzed. RESULTS: The ingestion of D1-10 resulted in the systemic presence of
      flavanols (plasma concentration: 863 +/- 77 nmol/L), gamma-VLs (24-h urine: 93 +/
      18 MUmol), and minute concentrations of procyanidin B2. With correction for
      small residual amounts of flavanols present in D2-10, only negligible
      concentrations of circulating flavanols were detected after ingestion of the
      drink, whereas the intake of D1 resulted in circulating flavanol concentrations
      similar to those detected after D1-10 consumption. CONCLUSIONS: These outcomes
      show that dietary procyanidins do not contribute to the systemic pool of
      flavanols in humans. Thus, these data reject the notion that procyanidins,
      through their breakdown into flavanols and subsequent absorption, causally
      modulate vascular function.

PMID- 22378734
TI  - Effects of n-3 PUFA supplementation on plasma soluble adhesion molecules: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Previous studies indicate that oral supplementation with n-3 PUFA
      protects against atherosclerotic disease by inhibiting inflammatory processes,
      which underlie atherosclerosis and are reflected by the plasma concentrations of
      soluble adhesion molecules. However, consistent results were not obtained among
      studies. OBJECTIVE: The objective was to assess the effects of n-3 PUFA
      supplementation on plasma concentrations of soluble adhesion molecules. DESIGN:
      We conducted a meta-analysis of randomized controlled trials identified from
      PubMed, Embase, the Cochrane Library, and reference lists of relevant articles
      and reviews. RESULTS: Eighteen studies were included. n-3 PUFA supplementation
      reduced plasma concentrations of soluble intercellular adhesion molecule-1 [sICAM
      1; weighted mean difference (WMD): -5.17; 95% CI: -10.07, -0.27; P = 0.04] but
      had no significant effects on soluble vascular cell adhesion molecule-1 (WMD: 
      5.90; 95% CI: -17.63, 5.84; P = 0.32), soluble P-selectin (WMD: -1.53; 95% CI: 
      4.33, 1.28; P = 0.29), or soluble E-selectin (WMD: 0.46; 95% CI: -1.54, 2.46; P =
      0.65). Subgroup analysis stratified by the subjects' health status showed that n
      3 PUFA supplementation reduced sICAM-1 concentrations in healthy subjects (WMD: 
      8.87; 95% CI: -15.20, -2.53; P = 0.006; heterogeneity test: I2 = 0%, P = 0.76)
      and in subjects with dyslipidemia (WMD: -15.31; 95% CI: -26.82, -3.81; P = 0.009;
      heterogeneity test: I2 = 26%, P = 0.26). CONCLUSIONS: n-3 PUFA supplementation
      can reduce plasma concentrations of sICAM-1. The effect is identified in both
      healthy subjects and subjects with dyslipidemia, which supports the hypothesis
      that n-3 PUFA can be supplemented as a primary or secondary means for preventing
      the development as well as the progression of atherosclerosis.

PMID- 22378735
TI  - Maternal Mthfd1 disruption impairs fetal growth but does not cause neural tube
      defects in mice.
AB  - BACKGROUND: MTHFD1 encodes C1-tetrahydrofolate synthase, which is a folate
      dependent enzyme that catalyzes the formation and interconversion of folate
      activated one-carbon groups for nucleotide biosynthesis and cellular methylation.
      A polymorphism in MTHFD1 (1958G->A) impairs enzymatic activity and is associated
      with increased risk of adverse pregnancy outcomes, but the mechanisms are
      unknown. OBJECTIVE: The objective of this study was to determine whether
      disruption of the embryonic or maternal Mthfd1 gene or both interacts with
      impaired folate and choline status to affect neural tube closure, fetal growth,
      and fertility in mice and to investigate the underlying metabolic disruptions.
      DESIGN: Dams with a gene-trapped (gt) allele in Mthfd1 and wild-type dams were
      fed a control or folate- and choline-deficient AIN93G diet (Dyets Inc). Litters
      were examined for gross morphologic defects, crown-rump length, and resorptions.
      Folate status and amounts of folate-related metabolites were determined in
      pregnant dams. RESULTS: Reduced folate and choline status resulted in severe
      fetal growth restriction (FGR) and impaired fertility in litters harvested from
      Mthfd1(gt/+) dams, but embryonic Mthfd1(gt/+) genotype did not affect fetal
      growth. Gestational supplementation of Mthfd1(gt/+) dams with hypoxanthine
      increased FGR frequency and caused occasional neural tube defects (NTDs) in
      Mthfd1(gt/+) embryos. Mthfd1(gt/+) dams exhibited lower red blood cell folate and
      plasma methionine concentrations than did wild-type dams. CONCLUSIONS: Maternal
      Mthfd1(gt/+) genotype impairs fetal growth but does not cause NTDs when dams are
      maintained on a folate- and choline-deficient diet. Mthfd1(gt/+) mice exhibit a
      spectrum of adverse reproductive outcomes previously attributed to the human
      MTHFD1 1958G->A polymorphism. Mthfd1 heterozygosity impairs folate status in
      pregnant mice but does not significantly affect homocysteine metabolism.

PMID- 22378736
TI  - Modulation of the association between plasma intercellular adhesion molecule-1
      and cancer risk by n-3 PUFA intake: a nested case-control study.
AB  - BACKGROUND: Mechanistic data suggest that n-3 PUFAs and endothelial function may
      interact and play a role in carcinogenesis, but epidemiologic evidence is
      lacking. OBJECTIVE: Our objective was to investigate whether the prospective
      association between soluble intercellular adhesion molecule-1 (sICAM-1) and
      cancer risk is modulated by n-3 PUFA intake. DESIGN: A nested case-control study
      was designed to include all first-incident cancer cases diagnosed in the
      SUpplementation en VItamines et Mineraux AntioXydants cohort between 1994 and
      2007, with available dietary data from 24-h records (n = 408). Cases were matched
      with 1 or 2 randomly selected controls (n = 760). Conditional logistic regression
      was used to estimate ORs and 95% CIs for the association between prediagnostic
      plasma concentrations of sICAM-1 and cancer risk, stratified by n-3 PUFA intake.
      The interactions between sICAM-1 and n-3 PUFA intake were tested. RESULTS: An
      interaction was observed between sICAM-1 and n-3 PUFA intake, which was
      consistent across the studied cancer locations (P-interaction = 0.036 for
      overall, 0.038 for breast, and 0.020 for prostate cancer risk). sICAM-1
      concentrations were positively associated with cancer risk among subjects with n
      3 PUFA intakes below the median (multivariate OR(Tertile3vsTertile1): 2.8; 95%
      CI: 1.5, 5.2; P-trend = 0.001), whereas this association was not observed for
      subjects with n-3 PUFA intakes above the median (OR(Tertile3vsTertile1): 1.3; 95%
      CI: 0.8, 2.3; P-trend = 0.3). CONCLUSION: These findings suggest that n-3 PUFA
      intake may counteract the procarcinogenic actions of sICAM-1.

PMID- 22378737
TI  - Methods for iPS cell generation for basic research and clinical applications.
AB  - The induction of pluripotency can be achieved by forced expression of defined
      factors in somatic cells. The established cells, termed induced pluripotent stem
      (iPS) cells, have pluripotency and an infinite capacity for self-renewal in
      common with embryonic stem (ES) cells. Patient-specific iPS cells could be a
      useful source for drug discovery and cell transplantation therapies; however, the
      original method for iPS cell generation had several issues that were obstacles to
      their clinical application. Recent studies have brought about various
      improvements for iPS cell generation and uncovered several characteristics of iPS
      cells. Here we summarize the current status of iPS cell studies, with a focus on
      the improved methods that can be used to generate iPS cells, and also refer to
      the future challenges.

PMID- 22378738
TI  - Primary care physicians' use of publicly reported quality data in hospital
      referral decisions.
AB  - BACKGROUND: Despite government investment in public reporting of hospital quality
      data, patients still rely on recommendations from their primary care physicians
      (PCPs). Little is known about how physicians make hospital referrals. OBJECTIVE:
      To characterize factors that influence PCPs' hospital referral choices. DESIGN:
      Web-based physician survey. PARTICIPANTS: PCPs affiliated with 3 Massachusetts
      hospitals. MAIN MEASURES: Physician demographics, familiarity with public
      reporting, and opinions about which factors would influence hospital referral
      decisions for an elderly patient with pneumonia. RESULTS: Of 194 PCPs who
      received invitations, 92 (47%) responded. Although 93% maintained admitting
      privileges, only 20% admitted patients. The following were considered "very"
      important in referral decisions: "familiarity with the hospital" (70%), "patient
      preference" (62%), and "admitting arrangements with a hospitalist group" (62%).
      "Publicly available quality measures" were "not at all" important to 42%. Only
      61% were aware of hospital quality reporting; 16% were familiar with Hospital
      Compare, a Centers for Medicare and Medicaid Services (CMS) Web site. No
      physicians reported ever using quality information to make a referral decision or
      discussing it with patients. No physician factors were associated with awareness
      of publicly reported data. PCPs identified the following factors as being "very"
      important in determining the quality of pneumonia care: antibiotics within 6
      hours of arrival (66%), appropriate initial antibiotic (63%), and blood cultures
      performed prior to the administration of antibiotics (51%). CONCLUSIONS: Although
      PCPs most valued the information available through Hospital Compare, only 16%
      were aware of it, and none used publicly reported quality data in referral
      decisions. Medicare and high-performing hospitals should consider marketing
      Hospital Compare to PCPs.

PMID- 22378739
TI  - Reaction kinetics in the plasma membrane.
AB  - A great puzzle in science is establishing a bottom up understanding of life by
      revealing how a collection of molecules gives rise to a living cell that can
      survive, communicate, and reproduce. In the confines of physics, chemistry, or
      material science laboratories where it possible to study complex interactions
      between molecules in a well-defined environment, our understanding of collective
      behavior is substantially developed. However, the environment in which molecules
      of a biological cell perform their functions is far from ideal or controllable.
      The environment inside cellular regions such as the plasma membrane is
      heterogeneous and dynamic, and functional molecules such as proteins are both
      dynamic and promiscuous, as they interact with countless other molecules. This
      makes it extremely challenging to grasp the inner mechanism of the cells, both
      experimentally and theoretically. On the bright side, this presents scientists
      with a colorful playground that waits to be explored: the mesoscopic world inside
      the cell. This review covers some of the recent experimental and theoretical
      developments in the study of molecular interactions in the plasma membrane,
      viewed as a heterogeneous medium where the number of reactants can be small,
      sometimes countable, and its implications for biological function.

PMID- 22378740
TI  - Ant attendance reduces flight muscle and wing size in the aphid Tuberculatus
      quercicola.
AB  - In otherwise mutualistic relationships between aphids and ants, attendance by
      ants often has negative impacts on aphids. For example, in a previous study using
      traps in the field, the aphid Tuberculatus quercicola, which exhibits mutualistic
      interactions with ants, showed extremely low dispersal rates, despite having long
      wings. This study investigates whether components of the flight apparatus
      (mesonotum length, flight muscle and wings) differ between aphids attended by
      ants and not attended by ants. Randomized block analysis of variance, using body
      length as a covariate, showed that ant attendance has a negative influence on
      aphid flight apparatus. This result indicates that aphids produce honeydew at the
      expense of resource investment in flight apparatus. Since the dispersal of T.
      quercicola is limited under ant attendance, the reduction in flight apparatus
      could precede a decrease in body size. This study also showed that flight
      apparatus was more developed in aphids under ant-exclusion conditions. This may
      imply that T. quercicola fly when ants are not available. The maintenance of
      flight apparatus in T. quercicola might therefore be partly explained by gene
      flow on the rare occasions that this aphid species disperses.

PMID- 22378741
TI  - Hermit crabs perceive the extent of their virtual bodies.
AB  - A flexible body image is required by animals if they are to adapt to body changes
      and move effectively within a structurally complex environment. Here, we show
      that terrestrial hermit crabs, Coenobita rugosus, which frequently change shells,
      can modify walking behaviour, dependent on the shape of the shell. Hermit crabs
      walked along a corridor that had alternating left and right corners; if it was
      narrow at the corner, crabs rotated their bodies to avoid the wall, indicating an
      awareness of environmental obstacles. This rotation increased when a plastic
      plate was attached to the shell. We suggest that the shell, when extended by the
      plate, becomes assimilated to the hermit crab's own body. While there are cases
      of a tool being assimilated with the body, our result is the first example of the
      habitat where an animal lives and/or carries being part of a virtual body.

PMID- 22378742
TI  - Estimating maximum bite performance in Tyrannosaurus rex using multi-body
      dynamics.
AB  - Bite mechanics and feeding behaviour in Tyrannosaurus rex are controversial. Some
      contend that a modest bite mechanically limited T. rex to scavenging, while
      others argue that high bite forces facilitated a predatory mode of life. We use
      dynamic musculoskeletal models to simulate maximal biting in T. rex. Models
      predict that adult T. rex generated sustained bite forces of 35 000-57 000 N at a
      single posterior tooth, by far the highest bite forces estimated for any
      terrestrial animal. Scaling analyses suggest that adult T. rex had a strong bite
      for its body size, and that bite performance increased allometrically during
      ontogeny. Positive allometry in bite performance during growth may have
      facilitated an ontogenetic change in feeding behaviour in T. rex, associated with
      an expansion of prey range in adults to include the largest contemporaneous
      animals.

PMID- 22378743
TI  - Habitat stability affects dispersal and the ability to track climate change.
AB  - Habitat persistence should influence dispersal ability, selecting for stronger
      dispersal in habitats of lower temporal stability. As standing (lentic)
      freshwater habitats are on average less persistent over time than running (lotic)
      habitats, lentic species should show higher dispersal abilities than lotic
      species. Assuming that climate is an important determinant of species
      distributions, we hypothesize that lentic species should have distributions that
      are closer to equilibrium with current climate, and should more rapidly track
      climatic changes. We tested these hypotheses using datasets from 1988 and 2006
      containing all European dragon- and damselfly species. Bioclimatic envelope
      models showed that lentic species were closer to climatic equilibrium than lotic
      species. Furthermore, the models over-predicted lotic species ranges more
      strongly than lentic species ranges, indicating that lentic species track
      climatic changes more rapidly than lotic species. These results are consistent
      with the proposed hypothesis that habitat persistence affects the evolution of
      dispersal.

PMID- 22378744
TI  - Modulation of Kv1.3 channels by protein kinase A I in T lymphocytes is mediated
      by the disc large 1-tyrosine kinase Lck complex.
AB  - The cAMP/PKA signaling system constitutes an inhibitory pathway in T cells and,
      although its biochemistry has been thoroughly investigated, its possible effects
      on ion channels are still not fully understood. K(V)1.3 channels play an
      important role in T-cell activation, and their inhibition suppresses T-cell
      function. It has been reported that PKA modulates K(V)1.3 activity. Two PKA
      isoforms are expressed in human T cells: PKAI and PKAII. PKAI has been shown to
      inhibit T-cell activation via suppression of the tyrosine kinase Lck. The aim of
      this study was to determine the PKA isoform modulating K(V)1.3 and the signaling
      pathway underneath. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a
      nonselective activator of PKA, inhibited K(V)1.3 currents both in primary human T
      and in Jurkat cells. This inhibition was prevented by the PKA blocker PKI(6-22).
      Selective knockdown of PKAI, but not PKAII, with siRNAs abolished the response to
      8-BrcAMP. Additional studies were performed to determine the signaling pathway
      mediating PKAI effect on K(V)1.3. Overexpression of a constitutively active
      mutant of Lck reduced the response of K(V)1.3 to 8-Br-cAMP. Moreover, knockdown
      of the scaffolding protein disc large 1 (Dlg1), which binds K(V)1.3 to Lck,
      abolished PKA modulation of K(V)1.3 channels. Immunohistochemistry studies showed
      that PKAI, but not PKAII, colocalizes with K(V)1.3 and Dlg1 indicating a close
      proximity between these proteins. These results indicate that PKAI selectively
      regulates K(V)1.3 channels in human T lymphocytes. This effect is mediated by Lck
      and Dlg1. We thus propose that the K(V)1.3/Dlg1/Lck complex is part of the
      membrane pathway that cAMP utilizes to regulate T-cell function.

PMID- 22378745
TI  - A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and
      p53 protein abundance in high glucose-exposed HepG2 cells.
AB  - AMP-activated protein kinase (AMPK) and the NAD(+)-dependent histone/protein
      deacetylase sirtuin 1 (SIRT1) are metabolic sensors that can increase each
      other's activity. They are also both activated by the antidiabetic drug metformin
      and downregulated in the liver under conditions of nutrient excess (e.g.,
      hyperglycemia, high-fat diet, obesity). In these situations, the abundance of the
      tumor suppressor p53 is increased; however, the relevance of this to the changes
      in AMPK and SIRT1 is not known. In the present study we investigated this
      question in HepG2 cells under high glucose conditions. Metformin induced
      activation of AMPK and SIRT1 and decreased p53 protein abundance. It also
      decreased triglyceride accumulation and cytosolic oxidative stress (a trigger for
      p53 accumulation) and increased the deacetylation of p53 at a SIRT1-targeted
      site. The decrease in p53 abundance caused by metformin was abolished by
      inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53
      degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA
      mediated knockdown of SIRT1. In addition, overexpression of p53 decreased SIRT1
      gene expression and protein abundance, as well as AMPK activity in metformin
      treated cells. It also diminished the triglyceride-lowering action of metformin,
      an effect that was rescued by incubation with the SIRT1 activator SRT2183.
      Collectively, these findings suggest the existence of a novel reciprocal
      interaction between AMPK/SIRT1 and p53 that may have implications for the
      pathogenesis and treatment of metabolic diseases.

PMID- 22378747
TI  - World Water Day: A global awareness campaign to tackle the water crisis.
AB  - World Water Day (WWD) has been celebrated on 22 March every year since 1993. It
      is an opportunity to learn more about water and its centrality in our lives and
      for the environment, and promote sustainable behaviours and actions towards this
      precious resource.

PMID- 22378746
TI  - Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid
      phosphatase associated with Lowe syndrome and Dent disease.
AB  - Oculocerebrorenal syndrome of Lowe (OCRL) gene product is a phosphatidyl inositol
      4,5-bisphosphate [PI(4,5)P(2)] 5-phosphatase, and mutations of OCRL cause Lowe
      syndrome and Dent disease, both of which are frequently associated with
      hypercalciuria. Transient receptor potential, vanilloid subfamily, subtype 6
      (TRPV6) is an intestinal epithelial Ca(2+) channel mediating active Ca(2+)
      absorption. Hyperabsorption of Ca(2+) was found in patients of Dent disease with
      increased Ca(2+) excretion. In this study, we tested whether TRPV6 is regulated
      by OCRL and, if so, to what extent it is altered by Dent-causing OCRL mutations
      using Xenopus laevis oocyte expression system. Exogenous OCRL decreased TRPV6
      mediated Ca(2+) uptake by regulating the function and trafficking of TRPV6
      through different domains of OCRL. The PI(4,5)P(2) 5-phosphatase domain
      suppressed the TRPV6-mediated Ca(2+) transport likely through regulating the
      PI(4,5)P(2) level needed for TRPV6 function without affecting TRPV6 protein
      abundance of TRPV6 at the cell surface. The forward trafficking of TRPV6 was
      decreased by OCRL. The Rab binding domain in OCRL was involved in regulating the
      trafficking of TRPV6. Knocking down endogenous X. laevis OCRL by antisense
      approach increased TRPV6-mediated Ca(2+) transport and TRPV6 forward trafficking.
      All seven Dent-causing OCRL mutations examined exhibited alleviation of the
      inhibitory effect on TRPV6-mediated Ca(2+) transport together with decreased
      overall PI(4,5)P(2) 5-phosphatase activity. In conclusion, OCRL suppresses TRPV6
      via two separate mechanisms. The disruption of PI(4,5)P(2) 5-phosphatase activity
      by Dent-causing mutations of OCRL may lead to increased intestinal Ca(2+)
      absorption and, in turn, hypercalciuria.

PMID- 22378748
TI  - On the origin of the enhanced acidity of chalcocyclopentadienes (cyclopentadiene
      chalcogenols) in the gas phase.
AB  - The intrinsic acidity of chalcocyclopentadienes (CpXH; X=O, S, Se, Te) is
      investigated by high-level G3B3 and G2 ab initio as well as B3LYP DFT
      calculations, which show that, independent of the nature of the heteroatom, all
      chalcocyclopentadienes are stronger acids in the gas phase than cyclopentadiene.
      However the acidity does not increase regularly down the group, and the acidity
      enhancement for Te derivatives is five times larger than for O derivatives, but
      only twice that of S-containing compounds. The most favorable deprotonation
      process corresponds to loss of the proton attached to the heteroatom, with the
      sole exception of the 5-substituted 1,3-cyclopentadienes, for which the O and S
      derivatives are predicted to behave as carbon acids. No matter the nature of the
      heteroatom, the 1-substituted 1,3-cyclopentadienes are the strongest acids. The
      intrinsic acidity of all isomers, namely, 1-substituted, 2-substituted, and 5
      substituted 1,3-cyclopentadienes, increases with increasing aromaticity of the
      anion formed on deprotonation, and therefore the Te compound is the strongest
      acid for the three series. However, the intrinsic acidity of
      chalcocyclopentadienes is not dictated by aromaticity, so that, in general, the
      most stable deprotonated species do not coincide with the most aromatic ones.

PMID- 22378749
TI  - Dramatic reduction of dimensionality in large biochemical networks owing to
      strong pair correlations.
AB  - Large multi-dimensionality of high-throughput datasets pertaining to cell
      signalling and gene regulation renders it difficult to extract mechanisms
      underlying the complex kinetics involving various biochemical compounds (e.g.
      proteins and lipids). Data-driven models often circumvent this difficulty by
      using pair correlations of the protein expression levels to produce a small
      number (fewer than 10) of principal components, each a linear combination of the
      concentrations, to successfully model how cells respond to different stimuli.
      However, it is not understood if this reduction is specific to a particular
      biological system or to nature of the stimuli used in these experiments. We study
      temporal changes in pair correlations, described by the covariance matrix,
      between concentrations of different molecular species that evolve following
      deterministic mass-action kinetics in large biologically relevant reaction
      networks and show that this dramatic reduction of dimensions (from hundreds to
      less than five) arises from the strong correlations between different species at
      any time and is insensitive to the form of the nonlinear interactions, network
      architecture, and to a wide range of values of rate constants and concentrations.
      We relate temporal changes in the eigenvalue spectrum of the covariance matrix to
      low-dimensional, local changes in directions of the system trajectory embedded in
      much larger dimensions using elementary differential geometry. We illustrate how
      to extract biologically relevant insights such as identifying significant
      timescales and groups of correlated chemical species from our analysis. Our work
      provides for the first time, to our knowledge, a theoretical underpinning for the
      successful experimental analysis and points to a way to extract mechanisms from
      large-scale high-throughput datasets.

PMID- 22378750
TI  - Dynamics and processing in finite self-similar networks.
AB  - A common feature of biological networks is the geometrical property of self
      similarity. Molecular regulatory networks through to circulatory systems, nervous
      systems, social systems and ecological trophic networks show self-similar
      connectivity at multiple scales. We analyse the relationship between topology and
      signalling in contrasting classes of such topologies. We find that networks
      differ in their ability to contain or propagate signals between arbitrary nodes
      in a network depending on whether they possess branching or loop-like features.
      Networks also differ in how they respond to noise, such that one allows for
      greater integration at high noise, and this performance is reversed at low noise.
      Surprisingly, small-world topologies, with diameters logarithmic in system size,
      have slower dynamical time scales, and may be less integrated (more modular) than
      networks with longer path lengths. All of these phenomena are essentially
      mesoscopic, vanishing in the infinite limit but producing strong effects at sizes
      and time scales relevant to biology.

PMID- 22378751
TI  - Cytogenetic biomonitoring in oral mucosa cells following dental X-ray.
AB  - OBJECTIVES: In the past decades, X-rays have been used widely for diagnosis in
      dentistry. However, it is well known that ionizing radiation causes damage
      (including single- and double-strand breaks) to deoxyribonucleic acid (DNA) and
      DNA-protein crosslinks, and induces cellular death. Therefore, outlining the
      cytogenetic effects induced by X-ray is necessary to identify the degree of
      cancer risk and minimize potential risks to patients and clinicians. To date, a
      variety of assays have been proposed in cytogenetic biomonitoring studies,
      including those that assess metaphase chromosomal aberrations and sister
      chromatid exchanges, and micronucleus and single-cell gel (comet) assay. METHODS:
      Cytogenetic biomonitoring studies focusing on oral mucosa cells in individuals
      exposed to dental X-ray were reviewed. RESULTS: Dental X-ray can induce DNA
      damage and cytotoxicity in oral mucosa cells. CONCLUSION: These results will
      contribute to a better understanding of X-ray-induced effects upon the cellular
      system in individuals continually exposed to known genotoxic/cytotoxic agents.

PMID- 22378752
TI  - A comparative study of accuracy of detection of surface osseous changes in the
      temporomandibular joint using multidetector CT and cone beam CT.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy and reliability of
      cone beam CT (CBCT) images compared with multidetector CT (MDCT) images for the
      detection of surface osseous changes in temporomandibular joints (TMJs). METHODS:
      Naked-eye inspection of 110 sites in 10 TMJs from 5 dry human skulls provided the
      gold standard. Two radiologists interpreted the images. Sensitivity, specificity
      and kappa statistics were used for analysis. RESULTS: The sensitivities of both
      modalities were low and comparable whereas the specificities were high and
      comparable. Intraobserver reliabilities for CBCT (p=0.0005) and for MDCT
      (p=0.0001) showed significant agreement. Interobserver reliability was higher for
      CBCT than for MDCT. CONCLUSION: CBCT and MDCT accuracy was comparable in
      detecting surface osseous changes with comparable intraobserver reliabilities.
      However, since CBCT requires less radiation exposure, it should be encouraged for
      imaging TMJ with suspected surface osseous changes.

PMID- 22378753
TI  - Effect of ambient light level at the monitor surface on digital radiographic
      evaluation of approximal carious lesions: an in vitro study.
AB  - OBJECTIVES: This study investigated how ambient light affects the diagnostic
      accuracy of dental carious lesions on monitors used in dental practice.
      Specifically, the aim was to evaluate whether a monitor hood for blocking excess
      ambient light increases practitioners' ability to accurately diagnose carious
      lesions on digital radiographs under bright ambient light conditions. METHODS: 7
      observers evaluated approximal carious lesions on standardized digital
      radiographs of 100 teeth under 3 ambient light conditions: bright light (> 1000
      lx) and dim light (<50 lx) with no monitor hood; and bright light with a hooded
      monitor. Receiver operating characteristic curves were plotted for all
      observations. The criterion standard was a histological examination of the teeth.
      A paired t-test compared the effects of the three lighting conditions. The level
      of significance was set to p <0.05. Weighted kappa statistics estimated
      intraobserver agreement. RESULTS: The diagnostic accuracy for dentine lesions was
      significantly higher in ambient light<50&hairsp ;lx than on monitors with and
      without a hood in ambient light>1000 lx. For all observers, diagnostic accuracy
      of dentine lesions under bright light was higher on a hooded monitor than on a
      monitor without a hood, but this difference was not significant. Intraobserver
      agreement varied from moderate to good. CONCLUSION: Diagnostic accuracy of those
      carious lesions that reached into the dentine was significantly higher in ambient
      light<50 lx than in ambient light>1000 lx. A hooded monitor in bright light was
      not as effective as a monitor without a hood in dim light.

PMID- 22378754
TI  - Characterization and correction of cupping effect artefacts in cone beam CT.
AB  - OBJECTIVE: The purpose of this study was to demonstrate and correct the cupping
      effect artefact that occurs owing to the presence of beam hardening and scatter
      radiation during image acquisition in cone beam CT (CBCT). METHODS: A uniform
      aluminium cylinder (6061) was used to demonstrate the cupping effect artefact on
      the Planmeca Promax 3D CBCT unit (Planmeca OY, Helsinki, Finland). The cupping
      effect was studied using a line profile plot of the grey level values using
      ImageJ software (National Institutes of Health, Bethesda, MD). A hardware-based
      correction method using copper pre-filtration was used to address this artefact
      caused by beam hardening and a software-based subtraction algorithm was used to
      address scatter contamination. RESULTS: The hardware-based correction used to
      address the effects of beam hardening suppressed the cupping effect artefact but
      did not eliminate it. The software-based correction used to address the effects
      of scatter resulted in elimination of the cupping effect artefact. CONCLUSION:
      Compensating for the presence of beam hardening and scatter radiation improves
      grey level uniformity in CBCT.

PMID- 22378755
TI  - Diagnostic accuracy on fat-saturated T2 weighted MRI for diagnosis of intra
      articular adhesions of the temporomandibular joint.
AB  - OBJECTIVE: The purpose of this study is to compare intra-articular adhesions of
      the temporomandibular joint (TMJ) between fat-saturated T2 weighted MR images and
      arthroscopic findings. METHODS: 50 patients (50 joints) with closed locking of
      the TMJ who were examined with MRI and then underwent arthroscopic surgery
      participated in this study. The concordance rate of intra-articular adhesions
      between fat-saturated T2 weighted MR images and arthroscopic findings was studied
      using the kappa coefficient. RESULTS: Intra-articular adhesions were seen on MRI
      in 21 joints (42%) and in arthroscopic findings in 26 joints (52%). Thus, five
      joints had false-negative results and mild adhesions were arthroscopically
      observed in these five joints. There was significant concordance between these
      two findings (p<0.001). The kappa coefficient was 0.801, which was considered to
      be complete concordance. CONCLUSIONS: On fat-saturated MRI, a low signal
      intensity area and narrowing image in the joint space of the TMJ may indicate the
      presence of intra-articular adhesions or fibrosis.

PMID- 22378756
TI  - Gigantiform cementoma in a child.
AB  - The objective of this report is to present an unusual case of a gigantiform
      cementoma manifesting with gross expansion of the maxilla in a 6-year-old black
      female. No history of similar lesions in the family of the patient was obtained.
      Radiographic examination revealed a well-circumscribed lobular radio-opaque mass
      surrounded by a radiolucent margin. The macroscopic specimen showed lobular
      mineralized masses with a "ginger root"-like appearance. Microscopic examination
      showed a lobular calcified mass with a peripheral zone of fibropsammomatous
      tissue corresponding with the radiolucent margin. The differential diagnoses,
      which include osteoma, ossifying fibroma and cementoblastoma, are discussed.

PMID- 22378757
TI  - NEUROG3 is a critical downstream effector for STAT3-regulated differentiation of
      mammalian stem and progenitor spermatogonia.
AB  - Spermatogenesis relies on coordinated differentiation of stem and progenitor
      spermatogonia, and the transcription factor STAT3 is essential for this process
      in mammals. Here we studied the THY1+ spermatogonial population in mouse testes,
      which contains spermatogonial stem cells (SSC) and non-stem cell progenitor
      spermatogonia, to further define the downstream mechanism regulating
      differentiation. Transcript abundance for the bHLH transcription factor Neurog3
      was found to be significantly reduced upon transient inhibition of STAT3
      signaling in these cells and exposure to GDNF, a key growth factor regulating
      self-renewal of SSCs, suppressed activation of STAT3 and in accordance Neurog3
      gene expression. Moreover, STAT3 was found to bind the distal Neurog3
      promoter/enhancer region in THY1+ spermatogonia and regulate transcription.
      Transient inhibition of Neurog3 expression in cultures of proliferating THY1+
      spermatogonia increased stem cell content after several self-renewal cycles
      without effecting overall proliferation of the cells, indicating impaired
      differentiation of SSCs to produce progenitor spermatogonia. Furthermore,
      cultured THY1+ spermatogonia with induced deficiency of Neurog3 were found to be
      incapable of differentiation in vivo following transplantation into testes of
      recipient mice. Collectively, these results establish a mechanism by which
      activation of STAT3 regulates the expression of NEUROG3 to subsequently drive
      differentiation of SSC and progenitor spermatogonia in the mammalian germline.

PMID- 22378758
TI  - Transgene-mediated rescue of spermatogenesis in Cldn11-null mice.
AB  - Claudins comprise a large family of tight junction (TJ) proteins that are often
      expressed broadly during development and in adult tissues and constitute the
      physical barriers that occlude the paracellular space in polarized epithelia. In
      mouse testis, the integrity of TJs is critical to normal spermatogenesis and is
      dependent on CLDN11 expression. In the current study, we have generated multiple
      transgenic mouse lines in which steady-state levels of transgene-derived Cldn11
      mRNA are up to fourfold greater than endogenous gene expression. Spermatogenesis
      in all founder mice harboring two copies of the endogenous Cldn11 gene is normal.
      These animals breed well, indicating that transgene overexpression, at least at
      the level of mRNA, is well tolerated by Sertoli cells. In addition, we
      demonstrate that the promoter/enhancer of the transgene, comprising 5 kb of
      genomic sequence upstream of exon 1 of the mouse Cldn11 gene, is sufficient to
      rescue azoospermia in Cldn11-null mice. Finally, using transient transgenic mice,
      we narrow the location of Sertoli cell-specific cis regulatory elements to a 2-kb
      region upstream of the Cldn11 transcription start site. Together, these data
      provide essential information for further investigation of the biological
      regulation of CLDN11 TJs in the testis.

PMID- 22378759
TI  - CDH1 is essential for endometrial differentiation, gland development, and adult
      function in the mouse uterus.
AB  - CDH1 is a cell-cell adhesion molecule expressed in the epithelium to coordinate
      key morphogenetic processes, establish cell polarity, and regulate epithelial
      differentiation and proliferation. To determine the role of CDH1 in the mouse
      uterus, Cdh1 was conditionally ablated by crossing Pgr-Cre and Cdh1-flox mice,
      and the phenotype was characterized. We found that loss of Cdh1 results in a
      disorganized cellular structure of the epithelium and ablation of endometrial
      glands in the neonatal uterus. Cdh1(d/d) mice lost adherens junctions (CTNNB1 and
      CTNNA1) and tight junctions (claudin, occludin, and ZO-1 proteins) in the
      neonatal uterus, leading to loss of epithelial cell-cell interaction. Ablation of
      Cdh1 induced abnormal epithelial proliferation and massive apoptosis, and
      disrupted Wnt and Hox gene expression in the neonatal uterus. Although the uteri
      of Cdh1(d/d) mice did not show any myometrial defects, ablation of Cdh1 inhibited
      expression of epithelial (cytokeratin 8) and stromal (CD10) markers. Cdh1(d/d)
      mice were infertile because of defects during implantation and decidualization.
      Furthermore, we showed in the model of conditional ablation of both Cdh1 and
      Trp53 in the uterus that interrupting cell cycle regulation through the loss of
      Cdh1 leads to abnormal uterine development. The uteri of Cdh1(d/d) Trp53(d/d)
      mice exhibited histological features of endometrial carcinomas with myometrial
      invasion. Collectively, these findings suggest that CDH1 has an important role in
      structural and functional development of the uterus as well as adult uterine
      function. CDH1 has a capacity to control cell fate by altering directional cell
      proliferation and apoptosis.

PMID- 22378760
TI  - Translation of incenp during oocyte maturation is required for embryonic
      development in Xenopus laevis.
AB  - The chromosome passenger complex (CPC) consists of Aurora-B kinase and several
      other subunits. One of these, incenp, binds Aurora-B and regulates its kinase
      activity. During Xenopus oocyte maturation, incenp accumulates through
      translation, contributing to aurora-b activation. A previous study has
      demonstrated that inhibition of incenp translation during oocyte maturation
      diminishes aurora-b activation but does not interfere with oocyte maturation,
      characterized by normal maturation-specific cyclin-b phosphorylation,
      degradation, and resynthesis. Here we have extended these findings, showing that
      inhibition of incenp translation during oocyte maturation did not interfere with
      meiosis I or II, as indicated by the normal emission of the first polar body and
      metaphase II arrest, followed by the successful emission of the second polar body
      upon parthenogenetic egg activation. Most importantly, however, when transferred
      to host frogs and subsequently ovulated, the incenp-deficient eggs were
      fertilized but failed to undergo mitotic cleavage. Thus, translation of incenp
      during oocyte maturation appears to be part of oocyte cytoplasmic maturation,
      preparing the egg for the rapid mitosis following fertilization.

PMID- 22378761
TI  - Preweaning over- and underfeeding alters onset of puberty in the rat without
      affecting kisspeptin.
AB  - The perinatal nutritional environment can permanently influence body weight,
      potentially leading to changes in puberty onset and reproductive function. We
      hypothesized that perinatal under- or overfeeding would alter puberty onset and
      influence concentrations of a neuropeptide crucial for successful puberty,
      kisspeptin. We manipulated Wistar rat litter sizes to derive small (SL), control
      (CL), and large (LL) litters containing 4, 12, and 20 rat pups respectively. This
      manipulation results in an overweight phenotype in SL rats and a lean phenotype
      in LL that persists throughout life. To investigate whether successful puberty
      onset is affected by neonatal under- or overfeeding, we examined indices of
      growth and development, including the onset of puberty, as well as the central
      expression of Kiss1 mRNA in these pups. Male LL rats reached puberty later than
      those from CL. These males also had reduced plasma testosterone and elevated
      17beta-estradiol concentrations at puberty. The age at puberty onset was not
      affected in SL males despite accelerated growth. In females, puberty onset was
      not significantly delayed by having a lean phenotype, and steroid hormones were
      not affected. The age at onset was, however, younger in the SL females. Kiss1
      mRNA in the hypothalamus was not affected by neonatal nutrition either at puberty
      or 7 days later. Our findings show early life underfeeding in males and
      overfeeding in females significantly affects puberty onset, altering steroid
      hormone concentrations in males, but this is not related to changes in
      hypothalamic kisspeptin.

PMID- 22378762
TI  - Amino acid turnover by bovine oocytes provides an index of oocyte developmental
      competence in vitro.
AB  - Amino acid profiling has been used to distinguish between human embryos of
      differing developmental competence. We sought to determine whether amino acid
      profiling could be used to distinguish between metaphase II (MII) bovine oocytes
      with different developmental capabilities in vitro. Amino acid turnover was
      assayed during the final 6 h of in vitro maturation prior to oocytes undergoing
      individual fertilization in vitro. Following insemination, zygotes were
      immobilized in groups of 16 on the base of a Petri dish using Cell-Tak tissue
      adhesive to enable the developmental progress of each to be tracked to the
      blastocyst stage. Spent droplets of in vitro maturation medium were analyzed by
      high performance liquid chromatography, which revealed glutamine, arginine, and
      asparagine were depleted in the greatest quantities. Incompetent MII oocytes that
      failed to cleave by 72 h postfertilization depleted significantly more glutamine
      from (P = 0.0006) and released more alanine (P = 0.0001) into the medium than
      oocytes that cleaved. When cutoff values were selected for the turnover of
      alanine, arginine, glutamine, leucine, and tryptophan and modeled to predict
      fertilization and cleavage potential, oocytes that did not exceed the cutoff
      values for >=2 of these key amino acids were more likely to cleave. The
      sensitivity, specificity, accuracy, and positive predictive value of this model
      were 60.5%, 76.8%, 63.5%, and 92.0%, respectively. Significant differences (P <=
      0.015) in the consumption/production of alanine and glutamine were also observed
      when comparing uncleaved oocytes with those that produced blastocysts. The data
      show that noninvasive amino acid profiling can be used to measure oocyte
      developmental competence.

PMID- 22378763
TI  - Transcriptional regulation of translocator protein (Tspo) via a SINE B2-mediated
      natural antisense transcript in MA-10 Leydig cells.
AB  - Translocator protein (18 kDa; TSPO) is a mitochondrial cholesterol- and drug
      binding protein involved in cholesterol import into mitochondria, the rate
      limiting step in steroidogenesis. TSPO is expressed at high levels in Leydig
      cells of the testis, and its expression levels dictate the ability of the cells
      to form androgen. In search of mechanisms that regulate Tspo expression, a number
      of transcription factors acting on its promoter region have been identified. We
      report herein the presence of a mechanism of regulation of Tspo expression via
      complementation with a natural antisense transcript (NAT). At the Tspo locus, a
      short interspersed repetitive element (SINE) of the SINE B2 family has the
      potential for high transcriptional activity. The extension of the SINE B2 element
      mediated transcript overlapped with exon 3 of the Tspo gene and formed a NAT
      specific for Tspo (Tspo-NAT) in MA-10 mouse tumor Leydig cells. The identified
      Tspo-NAT was also found in testis and kidney tissues. Overexpression of the Tspo
      NAT regulated Tspo gene expression and its function in steroid formation in MA-10
      cells. Time-course studies have indicated that Tspo-NAT expression is regulated
      by cAMP and could regulate TSPO levels to maintain optimal steroid production by
      MA-10 Leydig cells. Taken together, these results suggest a new micro
      transcriptional mechanism that regulates Tspo expression and thus steroidogenesis
      via an intron-based SINE B2-driven NAT specific for the Tspo gene.

PMID- 22378765
TI  - Microheterogeneities in ionic-liquid-methanol solutions studied by FTIR
      spectroscopy, DFT calculations and molecular dynamics simulations.
AB  - The interest in ionic liquids (ILs) is steadily increasing because of their
      fascinating physicochemical properties and because of their broad range of
      applications in synthesis, separation, catalysis and electrochemistry. However,
      the multiplicity of their uses strongly depends on a molecular understanding of
      their exceptional properties. One key to a better understanding of their unique
      properties are spectroscopic studies of ionic liquids in conventional organic
      solvents in combination with DFT calculations and molecular dynamics simulations.
      Therefore we investigated the mixtures of the imidazolium-based ionic liquid
      [C(2)mim][NTf(2)] with methanol. Caused by the amphiphilic character of methanol
      both liquids are miscible over the whole mixture range. The scope of this work is
      to study the changes in the IL network upon dilution and to investigate the
      formation of methanol clusters embedded in the IL matrix. The mixtures were
      studied by FTIR spectroscopy in the mid-infrared region. The formation of
      methanol clusters was studied from the OD stretching vibrational bands between
      2300 and 2800 cm(-1). The cluster populations of methanol could be derived from
      molecular dynamics simulations for the same mixtures. Weighting the DFT
      calculated frequencies by the cluster populations we could reproduce the measured
      spectra in the OD stretching region up to X(MeOH)=0.5. Above X(MeOH)=0.8, strong
      formation of self-methanol clusters takes place resulting in increasing diffusion
      coefficients related to decreasing dynamical heterogeneities. Thus we obtained a
      deep understanding of the solute-solvent and solute-solute interactions as well
      as information about the presence of microheterogeneities in the mixtures.

PMID- 22378764
TI  - NODAL in the uterus is necessary for proper placental development and maintenance
      of pregnancy.
AB  - Preterm birth is the single leading cause of perinatal mortality in developed
      countries, affecting approximately 12% of pregnancies and accounting for 75% of
      neonatal loss in the United States. Despite the prevalence and severity of
      premature delivery, the causes and mechanisms that underlie spontaneous and
      idiopathic preterm birth remain unknown. Our inability to elucidate these
      fundamental causes has been attributed to a poor understanding of the signaling
      pathways associated with the premature induction of parturition and a lack of
      suitable animal models available for preterm birth research. In this study, we
      describe the generation and analysis of a novel conditional knockout of the
      transforming growth factor beta (TGFB) superfamily member, Nodal, from the
      maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females
      exhibited a severe malformation of the maternal decidua basalis during
      placentation, leading to significant intrauterine growth restriction, and
      ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several
      approaches, we characterized aberrant placental development and demonstrated that
      reduced proliferation combined with increased apoptosis resulted in a diminished
      decidua basalis and compromised maternal-fetal interface. Last, we evaluated
      various components of the established parturition cascade and determined that
      preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX
      2) upregulation at the placental interface. Taken together, the results presented
      in this study highlight an in vivo role for maternal NODAL during placentation,
      present an interesting link between disrupted decidua basalis formation and
      premature parturition, and describe a potentially valuable model toward
      elucidating the complex processes that underlie preterm birth.

PMID- 22378767
TI  - An MD study of the applicability of the Walden rule and the Nernst-Einstein model
      for ionic liquids.
AB  - Six different ionic liquids containing imidazolium, pyrrolidinium and ammonium
      cations paired with bis[(trifluoromethyl)sulfonyl]imide and
      bis[(perfluoroethyl)sulfonyl]imide anions were studied using molecular dynamics
      simulations. Ionic conductivities, shear viscosities and self-diffusivities were
      computed and compared to see what relationships exist between these three
      transport properties. The simulations suggest that these ionic liquids follow
      closely the Walden rule, which relates ionic conductivity to fluidity. The
      computed ionic conductivities agree well with those predicted from the Nernst
      Einstein model, suggesting that long-time correlation among ion velocities is
      small, or that the "ionicity" of these ionic liquids is high.

PMID- 22378766
TI  - Mapping hidden potential identity elements by computing the average
      discriminating power of individual tRNA positions.
AB  - The recently published discrete mathematical method, extended consensus partition
      (ECP), identifies nucleotide types at each position that are strictly absent from
      a given sequence set, while occur in other sets. These are defined as
      discriminating elements (DEs). In this study using the ECP approach, we mapped
      potential hidden identity elements that discriminate the 20 different tRNA
      identities. We filtered the tDNA data set for the obligatory presence of well
      established tRNA features, and then separately for each identity set, the
      presence of already experimentally identified strictly present identity elements.
      The analysis was performed on the three kingdoms of life. We determined the
      number of DE, e.g. the number of sets discriminated by the given position, for
      each tRNA position of each tRNA identity set. Then, from the positional DE
      numbers obtained from the 380 pairwise comparisons of the 20 identity sets, we
      calculated the average excluding value (AEV) for each tRNA position. The AEV
      provides a measure on the overall discriminating power of each position. Using a
      statistical analysis, we show that positional AEVs correlate with the number of
      already identified identity elements. Positions having high AEV but lacking
      published identity elements predict hitherto undiscovered tRNA identity elements.

PMID- 22378768
TI  - Special issue on Pharmacogenetics.

PMID- 22378769
TI  - Do clinical and experimental investigations support an antiatherogenic role for
      dietary phytosterols/stanols?
AB  - The plasma cholesterol-reducing effect of phytosterols (PS) has been recognized
      in several studies, but the usefulness of PS in preventing coronary heart disease
      remains controversial, as some investigations claim that the high PS
      concentrations found in plasma and specific tissues are related to an increased
      risk of cardiovascular events. It has also been demonstrated that PS may induce
      inflammation and reduce cholesterol efflux from macrophages, conditions that are
      directly implicated in the development of atherosclerosis. As to arterial
      dysfunction and atherosclerosis, some studies have concluded that plasma PS
      concentrations are unrelated or only weakly related or that PS intake or plasma
      PS concentrations are harmful. Thus, in light of the National Cholesterol
      Education Program-ATPIII report, it is necessary to evaluate the relevance of
      their findings. To this end, we have evaluated the studies conducted on cells,
      animal models, and humans regarding the influence of PS on the development of
      atherosclerosis.

PMID- 22378770
TI  - Cryotherapy for plantar warts more costly but no more effective than salicylic
      acid self-treatment.

PMID- 22378771
TI  - Anterograde transneuronal viral tract tracing reveals central sensory circuits
      from brown fat and sensory denervation alters its thermogenic responses.
AB  - Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its
      sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory
      associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)]
      also suggest sensory innervation. The central nervous system (CNS) projections of
      BAT afferents are unknown. Therefore, we used the H129 strain of the herpes
      simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to
      delineate sensory nerve circuits, to define these projections. HSV-1 was injected
      into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity
      (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h
      groups had the most HSV-1-ir neurons with marked infections in the hypothalamic
      paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei,
      raphe nuclei, and reticular areas. These sites also are involved in sympathetic
      outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback
      circuits. We tested the functional contribution of IBAT sensory innervation on
      thermogenic responses to an acute (24 h) cold exposure test by injecting the
      specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring
      core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was
      significantly decreased in capsaicin-treated IBAT demonstrating successful
      sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in
      capsaicin-treated hamsters compared with the saline controls at 2 h of cold
      exposure. Thus the central sensory circuits from IBAT have been delineated for
      the first time, and impairment of sensory feedback from BAT appears necessary for
      the appropriate, initial thermogenic response to acute cold exposure.

PMID- 22378772
TI  - Voluntary running in mice beneficially modulates myocardial ischemic tolerance,
      signaling kinases, and gene expression patterns.
AB  - Exercise triggers hormesis, conditioning hearts against damaging consequences of
      subsequent ischemia-reperfusion (I/R). We test whether "low-stress" voluntary
      activity modifies I/R tolerance and molecular determinants of cardiac survival.
      Male C57BL/6 mice were provided 7-day access to locked (7SED) or rotating (7EX)
      running-wheels before analysis of cardiac prosurvival (Akt, ERK 1/2) and prodeath
      (GSK3beta) kinases, transcriptomic adaptations, and functional tolerance of
      isolated hearts to 25-min ischemia/45-min reperfusion. Over 7 days, 7EX mice
      increased running from 2.1 +/- 0.2 to 5.3 +/- 0.3 km/day (mean speed 38 +/- 2
      m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered
      43 +/- 3% of ventricular force with diastolic contracture of 33 +/- 3 mmHg,
      whereas 7EX hearts recovered 63 +/- 5% of force with diastolic dysfunction
      reduced to 23 +/- 2 mmHg (P < 0.05). Cytosolic expression (total protein) of Akt
      and GSK3beta was unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts.
      Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3beta
      phosphorylation increased ~90%. Microarray interrogation identified significant
      changes (>=1.3-fold expression change, <=5% FDR) in 142 known genes, the majority
      (92%) repressed. Significantly modified paths/networks related to
      inflammatory/immune function (particularly interferon-dependent), together with
      cell movement, growth, and death. Of only 14 induced transcripts, 3 encoded
      interrelated sarcomeric proteins titin, alpha-actinin, and myomesin-2, while
      transcripts for protective actin-stabilizing ND1-L and activator of mitochondrial
      biogenesis ALAS1 were also induced. There was no transcriptional evidence of
      oxidative heat-shock or other canonical "stress" responses. These data
      demonstrate that relatively brief voluntary activity substantially improves
      cardiac ischemic tolerance, an effect independent of shifts in Akt, but
      associated with increased total ERK 1/2 and phospho-inhibition of GSK3beta.
      Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in
      activity-dependent protection.

PMID- 22378773
TI  - Angiotensin II type 2 receptor-coupled nitric oxide production modulates free
      radical availability and voltage-gated Ca2+ currents in NTS neurons.
AB  - The medial region of the nucleus tractus solitarius (mNTS) is a key brain stem
      site controlling cardiovascular function, wherein ANG II modulates neuronal L
      type Ca(2+) currents via activation of ANG II type 1 receptors (AT(1)R) and
      production of reactive oxygen species (ROS). ANG II type 2 receptors (AT(2)R)
      induce production of nitric oxide (NO), which may interact with ROS and modulate
      AT(1)R signaling. We sought to determine whether AT(2)R-mediated NO production
      occurs in mNTS neurons and, if so, to elucidate the NO source and the functional
      interaction with AT(1)R-induced ROS or Ca(2+) influx. Electron microscopic (EM)
      immunolabeling showed that AT(2)R and neuronal NO synthase (nNOS) are coexpressed
      in neuronal somata and dendrites receiving synapses in the mNTS. In the presence
      of the AT(1)R antagonist losartan, ANG II increased NO production in isolated
      mNTS neurons, an effect blocked by the AT(2)R antagonist PD123319, but not the
      angiotensin (1-7) antagonist D-Ala. Studies in mNTS neurons of nNOS-null or
      endothelial NOS (eNOS)-null mice established nNOS as the source of NO. ANG II
      induced ROS production was enhanced by PD123319, the NOS inhibitor N(G)-nitro-l
      arginine (LNNA), or in nNOS-null mice. Moreover, in the presence of losartan, ANG
      II reduced voltage-gated L-type Ca(2+) current, an effect blocked by PD123319 or
      LNNA. We conclude that AT(2)R are closely associated and functionally coupled
      with nNOS in mNTS neurons. The resulting NO production antagonizes AT(1)R
      mediated ROS and dampens L-type Ca(2+) currents. The ensuing signaling changes in
      the NTS may counteract the deleterious effects of AT(1)R on cardiovascular
      function.

PMID- 22378774
TI  - Stretch-activated cation channel TRPV4 mediates hyposmotically induced prolactin
      release from prolactin cells of mozambique tilapia Oreochromis mossambicus.
AB  - In teleost fish, prolactin (PRL) is an important hormone for hyperosmoregulation.
      The release of PRL from the pituitary of Mozambique tilapia is stimulated by a
      decrease in extracellular osmolality. Previous studies have shown that
      hyposmotically induced PRL release is linked with cell volume changes, and that
      stretch-activated Ca(2+) channels are likely responsible for the initiation of
      the signal transduction for PRL release. In this study, we identified the stretch
      activated Ca(2+) channel transient receptor potential vanilloid 4 (TRPV4) from
      the rostral pars distalis (RPD) of tilapia acclimated to freshwater (FW). TRPV4
      transcripts were ubiquitously expressed in tilapia; the level of expression in
      RPDs of FW-acclimated fish was lower than that found in RPDs of seawater (SW)
      acclimated fish. Immunohistochemical analysis of the pituitary revealed that
      TRPV4 is localized in the cell membrane of PRL cells of both FW and SW tilapia. A
      functional assay with CHO-K1 cells showed that tilapia TRPV4 responded to a
      decrease in extracellular osmolality, and that its function was suppressed by
      ruthenium red (RR) and activated by 4alpha-phorbol 12,13-didecanoate (4aPDD).
      Exposure of dissociated PRL cells from FW-acclimated tilapia to RR blocked
      hyposmolality induced PRL release. PRL release, on the other hand, was stimulated
      by 4aPDD. These results indicate that PRL release in response to physiologically
      relevant changes in extracellular osmolality is mediated by the osmotically
      sensitive TRPV4 cation channel.

PMID- 22378775
TI  - Regulation of oxidative phosphorylation complex activity: effects of tissue
      specific metabolic stress within an allometric series and acute changes in
      workload.
AB  - The concentration of mitochondrial oxidative phosphorylation complexes (MOPCs) is
      tuned to the maximum energy conversion requirements of a given tissue; however,
      whether the activity of MOPCs is altered in response to acute changes in energy
      conversion demand is unclear. We hypothesized that MOPCs activity is modulated by
      tissue metabolic stress to maintain the energy-metabolism homeostasis. Metabolic
      stress was defined as the observed energy conversion rate/maximum energy
      conversion rate. The maximum energy conversion rate was assumed to be
      proportional to the concentration of MOPCs, as determined with optical
      spectroscopy, gel electrophoresis, and mass spectrometry. The resting metabolic
      stress of the heart and liver across the range of resting metabolic rates within
      an allometric series (mouse, rabbit, and pig) was determined from MPOCs content
      and literature respiratory values. The metabolic stress of the liver was high and
      nearly constant across the allometric series due to the proportional increase in
      MOPCs content with resting metabolic rate. In contrast, the MOPCs content of the
      heart was essentially constant in the allometric series, resulting in an
      increasing metabolic stress with decreasing animal size. The MOPCs activity was
      determined in native gels, with an emphasis on Complex V. Extracted MOPCs enzyme
      activity was proportional to resting metabolic stress across tissues and species.
      Complex V activity was also shown to be acutely modulated by changes in metabolic
      stress in the heart, in vivo and in vitro. The modulation of extracted MOPCs
      activity suggests that persistent posttranslational modifications (PTMs) alter
      MOPCs activity both chronically and acutely, specifically in the heart. Protein
      phosphorylation of Complex V was correlated with activity inhibition under
      several conditions, suggesting that protein phosphorylation may contribute to
      activity modulation with energy metabolic stress. These data are consistent with
      the notion that metabolic stress modulates MOPCs activity in the heart.

PMID- 22378776
TI  - Reduction of TIP47 improves hepatic steatosis and glucose homeostasis in mice.
AB  - Lipid droplets in the liver are coated with the perilipin family of proteins,
      notably adipocyte differentiation-related protein (ADRP) and tail-interacting
      protein of 47 kDa (TIP47). ADRP is increased in hepatic steatosis and is
      associated with hyperlipidemia, insulin resistance, and glucose intolerance. We
      have shown that reducing ADRP in the liver via antisense oligonucleotide (ASO)
      treatment attenuates steatosis and improves insulin sensitivity and glucose
      tolerance. We hypothesized that TIP47 has similar effects on hepatic lipid and
      glucose metabolism. We found that TIP47 mRNA and protein levels were increased in
      response to a high-fat diet (HFD) in C57BL/6J mice. TIP47 ASO treatment decreased
      liver TIP47 mRNA and protein levels without altering ADRP levels. Low-dose TIP47
      ASO (15 mg/kg) and high-dose TIP47 ASO (50 mg/kg) decreased triglyceride content
      in the liver by 35% and 52%, respectively. Liver histology showed a drastic
      reduction in hepatic steatosis following TIP47 ASO treatment. The high dose of
      TIP47 ASO significantly blunted hepatic triglyceride secretion, improved glucose
      tolerance, and increased insulin sensitivity in liver, adipose tissue, and
      muscle. These findings show that TIP47 affects hepatic lipid and glucose
      metabolism and may be a target for the treatment of nonalcoholic fatty liver and
      related metabolic disorders.

PMID- 22378777
TI  - Role of catalase on the hypoxia/reoxygenation stress in the hypoxia-tolerant Nile
      tilapia.
AB  - The specific contribution of each antioxidant enzyme to protection against the
      reoxygenation-associated oxidative stress after periods of hypoxia is not well
      understood. We assessed the physiological role of catalase during posthypoxic
      reoxygenation by the combination of two approaches. First, catalase activity of
      Nile tilapias (Oreochromis niloticus) was 90% suppressed by intraperitoneal
      injection of 3-amino-1,2,4-triazole (ATZ, 1g/kg). In ATZ-injected fish, liver GSH
      levels, oxidative stress markers, and activities of other antioxidant enzymes
      remained unchanged. Second, animals with depleted catalase activity (or those
      saline-injected) were subjected to a cycle of severe hypoxia (dissolved O(2) =
      0.28 mg/l for 3 h) followed by reoxygenation (0.5 to 24 h). Hypoxia did not
      induce changes in the above-mentioned parameters, either in saline- or in ATZ
      injected animals. Reoxygenation increased superoxide dismutase activity in saline
      injected fish, whose levels were similar to ATZ-injected animals. The activities
      of glutathione S-transferase, selenium-dependent glutathione peroxidase, and
      total-GPX and the levels of GSH-eq, GSSG, and thiobarbituric acid reactive
      substances remained unchanged during reoxygenation in both saline- and ATZ
      injected fish. The GSSG/GSH-eq ratio in ATZ-injected fish increased at 30 min of
      reoxygenation compared with saline-injected ones. Reoxygenation also increased
      carbonyl protein levels in saline-injected fish, whose levels were similar to the
      ATZ-injected group. Our work shows that inhibition of liver tilapia catalase
      causes a redox imbalance during reoxygenation, which is insufficient to induce
      further oxidative stress. This indicates the relevance of hepatic catalase for
      hypoxia/reoxygenation stress in tilapia fish.

PMID- 22378778
TI  - PpsR, a regulator of heme and bacteriochlorophyll biosynthesis, is a heme-sensing
      protein.
AB  - Heme-mediated regulation, presented in many biological processes, is achieved in
      part with proteins containing heme regulatory motif. In this study, we
      demonstrate that FLAG-tagged PpsR isolated from Rhodobacter sphaeroides cells
      contains bound heme. In vitro heme binding studies with tagless apo-PpsR show
      that PpsR binds heme at a near one-to-one ratio with a micromolar binding
      constant. Mutational and spectral assays suggest that both the second Per-Arnt
      Sim (PAS) and DNA binding domains of PpsR are involved in the heme binding.
      Furthermore, we show that heme changes the DNA binding patterns of PpsR and
      induces different responses of photosystem genes expression. Thus, PpsR functions
      as both a redox and heme sensor to coordinate the amount of heme,
      bacteriochlorophyll, and photosystem apoprotein synthesis thereby providing fine
      tune control to avoid excess free tetrapyrrole accumulation.

PMID- 22378779
TI  - Trans-Golgi Network (TGN) as a regulatory node for beta1-adrenergic receptor
      (beta1AR) down-modulation and recycling.
AB  - Receptor down-modulation is the key mechanism by which G protein-coupled
      receptors (GPCRs) prevent excessive receptor signaling in response to agonist
      stimulation. Recently, the trans-Golgi network (TGN) has been implicated as a key
      checkpoint for receptor endocytosis and degradation. Here, we investigated the
      involvement of the TGN in down-modulation of beta1-adrenergic receptor in
      response to persistent isoprotenerol stimulation. Immunofluorescent staining
      showed that ~50% of endocytosed beta1AR colocalized with TGN-46 at 5 h.
      Disruption of the TGN by brefeldin A (BFA) led to the robust accumulation of
      endocytosed beta1AR in Rab11(+) recycling endosomes, inhibited beta1AR entry into
      LAMP1(+) lysosomes, and as a result enhanced beta1AR recycling to the plasma
      membrane. The lysosomotropic agent, chloroquine, arrested the majority of
      endocytosed beta1AR in the TGN by 4 h. Immunoblot analysis showed that either
      disruption of the TGN or blockage of the lysosome prevented beta1AR degradation.
      Co-expression of GFP-arrestin-3 in beta1AR cells increased the endocytosis of
      beta1AR and facilitated its entry to the TGN but inhibited recycling to the
      plasma membrane. Arrestin-3-induced inhibition of beta1AR recycling was reversed
      by BFA treatment, whereas chloroquine induced the accumulation of arrestin-3 with
      beta1AR in the TGN. These results demonstrate for the first time that the TGN
      acts as a checkpoint for both the recycling and down-regulation of beta1AR and
      that arrestin-3 not only mediates beta1AR endocytosis but also its recycling
      through the TGN.

PMID- 22378780
TI  - Silent information regulator 2 (Sir2) and Forkhead box O (FOXO) complement
      mitochondrial dysfunction and dopaminergic neuron loss in Drosophila PTEN-induced
      kinase 1 (PINK1) null mutant.
AB  - PTEN-induced kinase 1 (PINK1), which is associated with early onset Parkinson
      disease, encodes a serine-threonine kinase that is critical for maintaining
      mitochondrial function. Moreover, another Parkinson disease-linked gene, parkin,
      functions downstream of PINK1 in protecting mitochondria and dopaminergic (DA)
      neuron. In our fly genetic screening, knockdown of Sir2 blocked PINK1
      overexpression-induced phenotypes. Consistently, ectopic expression of Sir2
      successfully rescued mitochondrial defects in PINK1 null mutants, but
      unexpectedly, failed in parkin mutants. In further genetic analyses, deletion of
      FOXO nullified the Sir2-induced mitochondrial restoration in PINK1 null mutants.
      Moreover, overexpression of FOXO or its downstream target gene such as SOD2 or
      Thor markedly ameliorated PINK1 loss-of-function defects, suggesting that FOXO
      mediates the mitochondrial protecting signal induced by Sir2. Consistent with its
      mitochondria-protecting role, Sir2 expression prevented the DA neuron loss of
      PINK1 null mutants in a FOXO-dependent manner. Loss of Sir2 or FOXO induced DA
      neuron degeneration, which is very similar to that of PINK1 null mutants.
      Furthermore, PINK1 deletion had no deleterious effect on the DA neuron loss in
      Sir2 or FOXO mutants, supporting the idea that Sir2, FOXO, and PINK1 protect DA
      neuron in a common pathway. Overall, these results strongly support the role of
      Sir2 and FOXO in preventing mitochondrial dysfunction and DA neuron loss, further
      suggesting that Sir2 and FOXO function downstream of PINK1 and independently of
      Parkin.

PMID- 22378781
TI  - Mechanisms of unphosphorylated STAT3 transcription factor binding to DNA.
AB  - Phosphorylation of signal transducer and activator of transcription 3 (STAT3) on
      a single tyrosine residue in response to growth factors, cytokines, interferons,
      and oncogenes activates its dimerization, translocation to the nucleus, binding
      to the interferon gamma (gamma)-activated sequence (GAS) DNA-binding site and
      activation of transcription of target genes. STAT3 is constitutively
      phosphorylated in various cancers and drives gene expression from GAS-containing
      promoters to promote tumorigenesis. Recently, roles for unphosphorylated STAT3 (U
      STAT3) have been described in response to cytokine stimulation, in cancers, and
      in maintenance of heterochromatin stability. However, the mechanisms underlying U
      STAT3 binding to DNA has not been fully investigated. Here, we explore STAT3-DNA
      interactions by atomic force microscopy (AFM) imaging. We observed that U-STAT3
      molecules bind to the GAS DNA-binding site as dimers and monomers. In addition,
      we observed that U-STAT3 binds to AT-rich DNA sequence sites and recognizes
      specific DNA structures, such as 4-way junctions and DNA nodes, within negatively
      supercoiled plasmid DNA. These structures are important for chromatin
      organization and our data suggest a role for U-STAT3 as a chromatin/genome
      organizer. Unexpectedly, we found that a C-terminal truncated 67.5-kDa STAT3
      isoform recognizes single-stranded spacers within cruciform structures that also
      have a role in chromatin organization and gene expression. This isoform appears
      to be abundant in the nuclei of cancer cells and, therefore, may have a role in
      regulation of gene expression. Taken together, our data highlight novel
      mechanisms by which U-STAT3 binds to DNA and supports U-STAT3 function as a
      transcriptional activator and a chromatin/genomic organizer.

PMID- 22378782
TI  - L-galactono-1,4-lactone dehydrogenase (GLDH) forms part of three subcomplexes of
      mitochondrial complex I in Arabidopsis thaliana.
AB  - L-galactono-1,4-lactone dehydrogenase (GLDH) catalyzes the terminal step of the
      Smirnoff-Wheeler pathway for vitamin C (l-ascorbate) biosynthesis in plants. A
      GLDH in gel activity assay was developed to biochemically investigate GLDH
      localization in plant mitochondria. It previously has been shown that GLDH forms
      part of an 850-kDa complex that represents a minor form of the respiratory NADH
      dehydrogenase complex (complex I). Because accumulation of complex I is disturbed
      in the absence of GLDH, a role of this enzyme in complex I assembly has been
      proposed. Here we report that GLDH is associated with two further protein
      complexes. Using native gel electrophoresis procedures in combination with the in
      gel GLDH activity assay and immunoblotting, two mitochondrial complexes of 470
      and 420 kDa were identified. Both complexes are of very low abundance. Protein
      identifications by mass spectrometry revealed that they include subunits of
      complex I. Finally, the 850-kDa complex was further investigated and shown to
      include the complete "peripheral arm" of complex I. GLDH is attached to a
      membrane domain, which represents a major fragment of the "membrane arm" of
      complex I. Taken together, our data further support a role of GLDH during complex
      I formation, which is based on its binding to specific assembly intermediates.

PMID- 22378783
TI  - Transcriptional induction of salt-inducible kinase 1 by transforming growth
      factor beta leads to negative regulation of type I receptor signaling in
      cooperation with the Smurf2 ubiquitin ligase.
AB  - Transforming growth factor beta (TGFbeta) regulates many physiological processes
      and requires control mechanisms to safeguard proper and timely action. We have
      previously described how negative regulation of TGFbeta signaling is controlled
      by the serine/threonine kinase salt-inducible kinase 1 (SIK1). SIK1 forms
      complexes with the TGFbeta type I receptor and with the inhibitory Smad7 and down
      regulates the type I receptor. We now demonstrate that TGFbeta induces SIK1
      levels via a direct transcriptional mechanism that implicates the Smad proteins,
      and we have mapped a putative enhancer element on the SIK1 gene. We provide
      evidence that the ubiquitin ligase Smurf2 forms complexes and functionally
      cooperates with SIK1. Both the kinase activity of SIK1 and the ubiquitin ligase
      activity of Smurf2 are important for proper type I receptor turnover. We also
      show that knockdown of endogenous SIK1 and Smurf2 enhances physiological
      signaling by TGFbeta that leads to epithelial growth arrest. In conclusion,
      TGFbeta induces expression of Smad7, Smurf2, and SIK1, the products of which
      physically and functionally interlink to control the activity of this pathway.

PMID- 22378784
TI  - Direct observation of translocation in individual DNA polymerase complexes.
AB  - Complexes of phi29 DNA polymerase and DNA fluctuate on the millisecond time scale
      between two ionic current amplitude states when captured atop the alpha-hemolysin
      nanopore in an applied field. The lower amplitude state is stabilized by
      complementary dNTP and thus corresponds to complexes in the post-translocation
      state. We have demonstrated that in the upper amplitude state, the DNA is
      displaced by a distance of one nucleotide from the post-translocation state. We
      propose that the upper amplitude state corresponds to complexes in the pre
      translocation state. Force exerted on the template strand biases the complexes
      toward the pre-translocation state. Based on the results of voltage and dNTP
      titrations, we concluded through mathematical modeling that complementary dNTP
      binds only to the post-translocation state, and we estimated the binding
      affinity. The equilibrium between the two states is influenced by active site
      proximal DNA sequences. Consistent with the assignment of the upper amplitude
      state as the pre-translocation state, a DNA substrate that favors the pre
      translocation state in complexes on the nanopore is a superior substrate in bulk
      phase for pyrophosphorolysis. There is also a correlation between DNA sequences
      that bias complexes toward the pre-translocation state and the rate of
      exonucleolysis in bulk phase, suggesting that during DNA synthesis the pathway
      for transfer of the primer strand from the polymerase to exonuclease active site
      initiates in the pre-translocation state.

PMID- 22378785
TI  - DnaJ (Hsp40 protein) binding to folded substrate impacts KplE1 prophage excision
      efficiency.
AB  - Temperate phages mediate gene transfer and can modify the properties of their
      host organisms through the acquisition of novel genes, a process called lysogeny.
      The KplE1 prophage is one of the 10 prophage regions in Escherichia coli K12
      MG1655. KplE1 is defective for lysis but fully competent for site-specific
      recombination. The TorI recombination directionality factor is strictly required
      for prophage excision from the host genome. We have previously shown that DnaJ
      promotes KplE1 excision by increasing the affinity of TorI for its site-specific
      recombination DNA target. Here, we provide evidence of a direct association
      between TorI and DnaJ using in vitro cross-linking assays and limited proteolysis
      experiments that show that this interaction allows both proteins to be
      transiently protected from trypsin digestion. Interestingly, NMR titration
      experiments showed that binding of DnaJ involves specific regions of the TorI
      structure. These regions, mainly composed of alpha-helices, are located on a
      surface opposite the DNA-binding site. Taken together, we propose that DnaJ,
      without the aid of DnaK/GrpE, is capable of increasing the efficiency of KplE1
      excision by causing a conformational stabilization that allows TorI to adopt a
      more favorable conformation for binding to its specific DNA target.

PMID- 22378786
TI  - Cellular pharmacology of protein kinase Mzeta (PKMzeta) contrasts with its in
      vitro profile: implications for PKMzeta as a mediator of memory.
AB  - A number of recent studies have used pharmacological inhibitors to establish a
      role for protein kinase Mzeta (PKMzeta) in synaptic plasticity and memory. These
      studies use zeta inhibitory peptide (ZIP) and chelerythrine as inhibitors of
      PKMzeta to block long term potentiation and memory; staurosporine is used as a
      negative control to show that a nonspecific kinase inhibitor does not block long
      term potentiation and memory. Here, we show that neither ZIP nor chelerythrine
      inhibits PKMzeta in cultured cells or brain slices. In contrast, staurosporine
      does block PKMzeta activity in cells and brain slices by inhibiting its upstream
      phosphoinositide-dependent kinase-1. These studies demonstrate that the
      effectiveness of drugs against purified PKMzeta may not be indicative of their
      specificity in the more complex environment of the cell and suggest that PKMzeta
      is unlikely to be the mediator of synaptic plasticity or memory.

PMID- 22378787
TI  - Fibroblast growth factor-21 (FGF21) regulates low-density lipoprotein receptor
      (LDLR) levels in cells via the E3-ubiquitin ligase Mylip/Idol and the Canopy2
      (Cnpy2)/Mylip-interacting saposin-like protein (Msap).
AB  - The LDLR is a critical factor in the regulation of blood cholesterol levels that
      are altered in different human diseases. The level of LDLR in the cell is
      regulated by both transcriptional and post-transcriptional events. The E3
      ubiquitin ligase, myosin regulatory light chain-interacting protein
      (Mylip)/inducible degrader of the LDL-R (Idol) was shown to induce degradation of
      LDLR via protein ubiquitination. We have here studied novel factors and
      mechanisms that may regulate Mylip/Idol in human hepatocyte cells and in mouse
      macrophages. We observed that FGF21 that is present in serum in different
      conditions reduced Mylip/Idol at the RNA and protein level, and increased LDLR
      levels and stability in the cells. FGF21 also enhanced expression of Canopy2
      (Cnpy2)/MIR-interacting Saposin-like protein (Msap) that is known to interact
      with Mylip/Idol. Overexpression of Cnpy2/Msap increased LDLRs, and knockdown
      experiments showed that Cnpy2/Msap is crucial for the FGF21 effect on LDLRs.
      Experiments using DiI-labeled LDL particles showed that FGF21 increased
      lipoprotein uptake and the effect of FGF21 was additive to that of statins. Our
      results are consistent with an important role of FGF21 and Cnpy2/Msap in the
      regulation of LDLRs in cultured cells, which warrants further studies using human
      samples.

PMID- 22378788
TI  - Combined analysis of microRNome and 3'-UTRome reveals a species-specific
      regulation of progesterone receptor expression in the endometrium of rhesus
      monkey.
AB  - The establishment of endometrial receptivity is a prerequisite for successful
      pregnancy, which is controlled by a complex mechanism. MicroRNAs (miRNAs) are
      small non-coding RNAs that have emerged as important regulators of gene
      expression. However, the contribution of miRNAs in endometrial receptivity is
      still unknown. Here we used rhesus monkey as an animal model and compared the
      endometrial miRNA expression profiles during early-secretory (pre-receptive)
      phase and mid-secretory (receptive) phase by deep sequencing. A set of
      differentially expressed miRNAs were identified, 8 of which were selected and
      validated using quantitative RT-PCR. To facilitate the prediction of their target
      genes, the 3'-UTRome was also determined using tag sequencing of mRNA 3'-termini.
      Surprisingly, about 50% of the 10,677 genes expressed in the rhesus monkey
      endometrium exhibited alternative 3'-UTRs. Of special interest, the progesterone
      receptor (PGR) gene, which is necessary for endometrial receptivity, processes an
      ultra long 3'-UTR (~10 kb) along with a short variant (~2.5 kb). Evolutionary
      analysis showed that the 3'-UTR sequences of PGR are poorly conserved between
      primates and rodents, suggesting a species-biased miRNA binding pattern. We
      further demonstrated that PGR is a valid target of miR-96 in rhesus monkey and
      human but not in rodents, whereas the regulation of PGR by miR-375 is rhesus
      monkey-specific. Additionally, we found that miR-219-5p regulates PGR expression
      through a primate-specific long non-coding RNA immediately downstream of the PGR
      locus. Our study provides new insights into the molecular mechanisms underlying
      endometrial receptivity and presents intriguing species-specific regulatory roles
      of miRNAs.

PMID- 22378789
TI  - Further in vitro exploration fails to support the allosteric three-site model.
AB  - Ongoing debate in the ribosome field has focused on the role of bound E-site tRNA
      and the Shine-Dalgarno-anti-Shine-Dalgarno (SD-aSD) interaction on A-site tRNA
      interactions and the fidelity of tRNA selection. Here we use an in vitro
      reconstituted Escherichia coli translation system to explore the reported effects
      of E-site-bound tRNA and SD-aSD interactions on tRNA selection events and find no
      evidence for allosteric coupling. A large set of experiments exploring the role
      of the E-site tRNA in miscoding failed to recapitulate the observations of
      earlier studies (Di Giacco, V., Marquez, V., Qin, Y., Pech, M., Triana-Alonso, F.
      J., Wilson, D. N., and Nierhaus, K. H. (2008) Proc. Natl. Acad. Sci. U.S.A. 105,
      10715-10720 and Geigenmuller, U., and Nierhaus, K. H. (1990) EMBO J. 9, 4527
      4533); the frequency of miscoding was unaffected by the presence of E-site-bound
      cognate tRNA. Moreover, our data provide clear evidence that the reported effects
      of the SD-aSD interaction on fidelity can be attributed to the binding of
      ribosomes to an unanticipated site on the mRNA (in the absence of the SD
      sequence) that provides a cognate pairing codon leading naturally to
      incorporation of the purported "noncognate" amino acid.

PMID- 22378790
TI  - ATP binding site mutagenesis reveals different subunit stoichiometry of
      functional P2X2/3 and P2X2/6 receptors.
AB  - The aim of the present experiments was to clarify the subunit stoichiometry of
      P2X2/3 and P2X2/6 receptors, where the same subunit (P2X2) forms a receptor with
      two different partners (P2X3 or P2X6). For this purpose, four non-functional Ala
      mutants of the P2X2, P2X3, and P2X6 subunits were generated by replacing single,
      homologous amino acids particularly important for agonist binding. Co-expression
      of these mutants in HEK293 cells to yield the P2X2 WT/P2X3 mutant or P2X2
      mutant/P2X3 WT receptors resulted in a selective blockade of agonist responses in
      the former combination only. In contrast, of the P2X2 WT/P2X6 mutant and P2X2
      mutant/P2X6 WT receptors, only the latter combination failed to respond to
      agonists. The effects of alpha,beta-methylene-ATP and 2-methylthio-ATP were
      determined by measuring transmembrane currents by the patch clamp technique and
      intracellular Ca(2+) transients by the Ca(2+)-imaging method. Protein labeling,
      purification, and PAGE confirmed the assembly and surface trafficking of the
      investigated WT and WT/mutant combinations in Xenopus laevis oocytes. In
      conclusion, both electrophysiological and biochemical investigations uniformly
      indicate that one subunit of P2X2 and two subunits of P2X3 form P2X2/3
      heteromeric receptors, whereas two subunits of P2X2 and one subunit of P2X6
      constitute P2X2/6 receptors. Further, it was shown that already two binding sites
      of the three possible ones are sufficient to allow these receptors to react with
      their agonists.

PMID- 22378791
TI  - Functional consequence of covalent reaction of phosphoenolpyruvate with UDP-N
      acetylglucosamine 1-carboxyvinyltransferase (MurA).
AB  - The enzyme MurA has been an established antibiotic target since the discovery of
      fosfomycin, which specifically inhibits MurA by covalent modification of the
      active site residue Cys-115. Early biochemical studies established that Cys-115
      also covalently reacts with substrate phosphoenolpyruvate (PEP) to yield a
      phospholactoyl adduct, but the structural and functional consequences of this
      reaction remained obscure. We captured and depicted the Cys-115-PEP adduct of
      Enterobacter cloacae MurA in various reaction states by X-ray crystallography.
      The data suggest that cellular MurA predominantly exists in a tightly locked
      complex with UDP-N-acetylmuramic acid (UNAM), the product of the MurB reaction,
      with PEP covalently attached to Cys-115. The uniqueness and rigidity of this
      "dormant" complex was previously not recognized and presumably accounts for the
      failure of drug discovery efforts toward the identification of novel and
      effective MurA inhibitors. We demonstrate that recently published crystal
      structures of MurA from various organisms determined by different laboratories
      were indeed misinterpreted and actually contain UNAM and covalently bound PEP.
      The Cys-115-PEP adduct was also captured in vitro during the reaction of free
      MurA and substrate UDP-N-acetylglucosamine or isomer UDP-N-acetylgalactosamine.
      The now available series of crystal structures allows a comprehensive view of the
      reaction cycle of MurA. It appears that the covalent reaction of MurA with PEP
      fulfills dual functions by tightening the complex with UNAM for the efficient
      feedback regulation of murein biosynthesis and by priming the PEP molecule for
      instantaneous reaction with substrate UDP-N-acetylglucosamine.

PMID- 22378792
TI  - Signal transducer and activator of transcription-5 mediates neuronal apoptosis
      induced by inhibition of Rac GTPase activity.
AB  - In several neuronal cell types, the small GTPase Rac is essential for survival.
      We have shown previously that the Rho family GTPase inhibitor Clostridium
      difficile toxin B (ToxB) induces apoptosis in primary rat cerebellar granule
      neurons (CGNs) principally via inhibition of Rac GTPase function. In the present
      study, incubation with ToxB activated a proapoptotic Janus kinase (JAK)/signal
      transducer and activator of transcription (STAT) pathway, and a pan-JAK inhibitor
      protected CGNs from Rac inhibition. STAT1 expression was induced by ToxB;
      however, CGNs from STAT1 knock-out mice succumbed to ToxB-induced apoptosis as
      readily as wild-type CGNs. STAT3 displayed enhanced tyrosine phosphorylation
      following treatment with ToxB, and a reputed inhibitor of STAT3, cucurbitacin
      (JSI-124), reduced CGN apoptosis. Unexpectedly, JSI-124 failed to block STAT3
      phosphorylation, and CGNs were not protected from ToxB by other known STAT3
      inhibitors. In contrast, STAT5A tyrosine phosphorylation induced by ToxB was
      suppressed by JSI-124. In addition, roscovitine similarly inhibited STAT5A
      phosphorylation and protected CGNs from ToxB-induced apoptosis. Consistent with
      these results, adenoviral infection with a dominant negative STAT5 mutant, but
      not wild-type STAT5, significantly decreased ToxB-induced apoptosis of CGNs.
      Finally, chromatin immunoprecipitation with a STAT5 antibody revealed increased
      STAT5 binding to the promoter region of prosurvival Bcl-xL. STAT5 was recruited
      to the Bcl-xL promoter region in a ToxB-dependent manner, and this DNA binding
      preceded Bcl-xL down-regulation, suggesting transcriptional repression. These
      data indicate that a novel JAK/STAT5 proapoptotic pathway significantly
      contributes to neuronal apoptosis induced by the inhibition of Rac GTPase.

PMID- 22378793
TI  - Biosynthesis of threonylcarbamoyl adenosine (t6A), a universal tRNA nucleoside.
AB  - The anticodon stem-loop (ASL) of transfer RNAs (tRNAs) drives decoding by
      interacting directly with the mRNA through codon/anticodon pairing. Chemically
      complex nucleoside modifications found in the ASL at positions 34 or 37 are known
      to be required for accurate decoding. Although over 100 distinct modifications
      have been structurally characterized in tRNAs, only a few are universally
      conserved, among them threonylcarbamoyl adenosine (t(6)A), found at position 37
      in the anticodon loop of a subset of tRNA. Structural studies predict an
      important role for t(6)A in translational fidelity, and in vivo work supports
      this prediction. Although pioneering work in the 1970s identified the fundamental
      substrates for t(6)A biosynthesis, the enzymes responsible for its biosynthesis
      have remained an enigma. We report here the discovery that in bacteria four
      proteins (YgjD, YrdC, YjeE, and YeaZ) are both necessary and sufficient for t(6)A
      biosynthesis in vitro. Notably, YrdC and YgjD are members of universally
      conserved families that were ranked among the top 10 proteins of unknown function
      in need of functional characterization, while YeaZ and YjeE are specific to
      bacteria. This latter observation, coupled with the essentiality of all four
      proteins in bacteria, establishes this pathway as a compelling new target for
      antimicrobial development.

PMID- 22378795
TI  - Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4
      aminobiphenyl.
AB  - 4-Aminobiphenyl, a known carcinogen, has many environmental sources like
      cigarette smoke, industrial waste, and so forth. It can be metabolized to form a
      potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes
      further processing to form electrophilic nitrenium ions which interact with DNA
      forming covalent adducts, thereby exerting genotoxic effects. While the
      mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been
      performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study,
      human placental DNA was modified with N-OH-AABP, and the structural perturbations
      in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1
      digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing
      female rabbits. The modified DNA was found to be highly immunogenic, eliciting
      high titer immunogen-specific antibodies, while the native form was almost
      nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in
      recognizing various nucleic acid conformers and DNA bases. We also detected
      deposits of immune complex in glomerular basement membrane in rabbits immunized
      with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies
      in cancer patients and the related consequences have been discussed.

PMID- 22378794
TI  - Fast modulation of MU-opioid receptor (MOR) recycling is mediated by receptor
      agonists.
AB  - The MU-opioid receptor (MOR) is a member of the G protein-coupled receptor family
      and the main target of endogenous opioid neuropeptides and morphine. Upon
      activation by ligands, MORs are rapidly internalized via clathrin-coated pits in
      heterologous cells and dissociated striatal neurons. After initial endocytosis,
      resensitized receptors recycle back to the cell surface by vesicular delivery for
      subsequent cycles of activation. MOR trafficking has been linked to opioid
      tolerance after acute exposure to agonist, but it is also involved in the
      resensitization process. Several studies describe the regulation and mechanism of
      MOR endocytosis, but little is known about the recycling of resensitized
      receptors to the cell surface. To study this process, we induced internalization
      of MOR with [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) and morphine
      and imaged in real time single vesicles recycling receptors to the cell surface.
      We determined single vesicle recycling kinetics and the number of receptors
      contained in them. Then we demonstrated that rapid vesicular delivery of
      recycling MORs to the cell surface was mediated by the actin-microtubule
      cytoskeleton. Recycling was also dependent on Rab4, Rab11, and the Ca(2+)
      sensitive motor protein myosin Vb. Finally, we showed that recycling is acutely
      modulated by the presence of agonists and the levels of cAMP. Our work identifies
      a novel trafficking mechanism that increases the number of cell surface MORs
      during acute agonist exposure, effectively reducing the development of opioid
      tolerance.

PMID- 22378796
TI  - Putting risk prediction in atrial fibrillation into perspective.

PMID- 22378799
TI  - Diet and Nutrition in Palliative Care.

PMID- 22378798
TI  - A.S.P.E.N. position paper: Clinical role for alternative intravenous fat
      emulsions.
AB  - The currently available, standard soybean oil (SO)-based intravenous fat
      emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients.
      There are alternative oil-based fat emulsions, such as medium-chain triglycerides
      (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in
      Europe, have an equivalent safety profile to SO. These alternative IVFEs are
      metabolized via different pathways, which may lead to less proinflammatory
      effects and less immune suppression. These alternative oil-based IVFEs are not
      currently available in the United States. Many patients who require IVFEs are
      already in a compromised state. Such patients could potentially have better
      clinical outcomes when receiving one of the alternative IVFEs to diminish the
      intake of the potentially proinflammatory omega-6 fatty acid-linoleic acid-which
      comprises more than 50% of the fatty acid profile in SO. Further research is
      needed on these alternative oil-based IVFEs to identify which IVFE oils or which
      combination of oils may be most clinically useful for specific patient
      populations.

PMID- 22378800
TI  - Preventing bacteria-induced disease with bacteria.
AB  - Oral administration of a probiotic preparation was shown to be effective in
      preventing the recurrence of chronic pouchitis in a classic double-blind, placebo
      controlled trial. This was a novel and unique approach to the care of these
      patients. Dysbiosis, a condition of microbial imbalance, has been implicated in
      the pathogenesis of inflammatory bowel disease. Rather than administering
      antibiotics to treat the microflora with each relapse of pouchitis, the emphasis
      was placed on preventing chronic flare-ups by administering probiotics to correct
      dysbiosis. The paradigm was shifted from treatment to prevention and from
      antibiotics to probiotics. These data were validated by this same group and
      others in subsequent trials. However, despite the promising results, many
      questions will need to be answered before routine use becomes universally
      accepted. The exact etiology and pathophysiology of pouchitis have not been fully
      elucidated. In addition, the choice of bacteria, optimal dose, and timing of
      administration have yet to be determined. Finally, the mechanisms by which
      probiotics provide their beneficial effects remain unresolved.

PMID- 22378797
TI  - Of microbes and meals: the health consequences of dietary endotoxemia.
AB  - The human intestinal tract comprises a rich and complex microbial ecosystem. This
      intestinal microbota provides a large reservoir of potentially toxic molecules,
      including bacterial endotoxin (ie, lipopolysaccharide [LPS]). This potent
      inflammatory molecule is detectable in the circulation of healthy individuals,
      and levels transiently increase following ingestion of energy-rich meals. Chronic
      exposure to circulating endotoxin has been associated with obesity, diabetes, and
      cardiovascular disease. Western-style meals augment LPS translocation and by this
      mechanism may contribute to the pathogenesis of these diseases. By contrast, the
      gut and other organs have evolved mechanisms to detoxify endotoxin and neutralize
      the potentially inflammatory qualities of circulating endotoxin. Of specific
      interest to clinicians is evidence that acute postprandial elevation of
      circulating endotoxin is dependent on meal composition. In this review, the
      authors present an overview of the biochemical and cellular mechanisms that lead
      to endotoxemia, with emphasis on the interplay between microbial and nutrition
      determinants of this condition. The link between endotoxemia, diet, and changes
      in the intestinal microbiota raise the possibility that dietary interventions
      can, at least in part, ameliorate the detrimental outcomes of endotoxemia.

PMID- 22378801
TI  - High waste contributes to low food intake in hospitalized patients.
AB  - BACKGROUND: The prevalence of disease-related malnutrition in hospital inpatients
      is high; many patients do not meet individual nutrition requirements while
      hospitalized. To better understand the reasons for inadequate nutrition intake,
      this study describes patient satisfaction, food provision, food intake, and waste
      of hospital meals. METHODS: Over 6 days, 150 hospital meals were weighed and
      nutrient composition was calculated. On return from the wards, waste was weighed.
      In addition, nutrition intake was compared to nutrition requirements in 42
      patients. In a separate study, the authors studied patient satisfaction with the
      hospital food service using interviews (n = 112). RESULTS: The 3 main meals
      accounted for a mean of 1809 +/- 143 kcal and 76 +/- 13 g of protein per day. In
      total, 38% of the food provided by the kitchen was wasted. As a consequence, the
      main meals supplied an average of 1105 +/- 594 kcal and 47 +/- 27 g of protein to
      patients. Sixty-one percent of patients had an energy intake <90% and 75% had a
      protein intake <90% of requirements. Most patients were satisfied or fairly
      satisfied with the choices, taste, and presentation of the main meals.
      Satisfaction with snack meals and information was inadequate. CONCLUSIONS: The
      standard meals provided by the hospital kitchen provide adequate amounts of
      energy and protein. However, most patients do not consume complete meals. It may
      be concluded that food waste is largely attributed to the inadequate intake of
      many hospitalized patients. Patients who experienced the worst health status ate
      the least.

PMID- 22378802
TI  - How the type of anthropogenic change alters the consequences of ecological traps.
AB  - Understanding altered ecological and evolutionary dynamics in novel environments
      is vital for predicting species responses to rapid environmental change. One
      fundamental concept relevant to such dynamics is the ecological trap, which
      arises from rapid anthropogenic change and can facilitate extinction. Ecological
      traps occur when formerly adaptive habitat preferences become maladaptive because
      the cues individuals preferentially use in selecting habitats lead to lower
      fitness than other alternatives. While it has been emphasized that traps can
      arise from different types of anthropogenic change, the resulting consequences of
      these different types of traps remain unknown. Using a novel model framework that
      builds upon the Price equation from evolutionary genetics, we provide the first
      analysis that contrasts the ecological and evolutionary consequences of
      ecological traps arising from two general types of perturbations known to trigger
      traps. Our model suggests that traps arising from degradation of existing
      habitats are more likely to facilitate extinction than those arising from the
      addition of novel trap habitat. Importantly, our framework reveals the mechanisms
      of these outcomes and the substantial scope for persistence via rapid evolution
      that may buffer many populations from extinction, helping to resolve the paradox
      of continued persistence of many species in dramatically altered landscapes.

PMID- 22378803
TI  - On the dispersal of leatherback turtle hatchlings from Mesoamerican nesting
      beaches.
AB  - So little is known about the early life history of leatherback turtles
      (Dermochelys coriacea) from hatchling to adulthood that this period has been
      termed the 'lost years'. For critically endangered eastern Pacific leatherback
      populations, continued and rapid declines underscore the urgent need to develop
      conservation strategies across all life stages. We investigate leatherback
      hatchling dispersal from four Mesoamerican nesting beaches using passive tracer
      experiments within a regional ocean modelling system. The evolution of tracer
      distribution from each of the nesting beaches showed the strong influence of eddy
      transport and coastal currents. Modelled hatchlings from Playa Grande, Costa
      Rica, were most likely to be entrained and transported offshore by large-scale
      eddies coincident with the peak leatherback nesting and hatchling emergence
      period. These eddies potentially serve as 'hatchling highways', providing a means
      of rapid offshore transport away from predation and a productive refuge within
      which newly hatched turtles can develop. We hypothesize that the most important
      leatherback nesting beach remaining in the eastern Pacific (Playa Grande) has
      been evolutionarily selected as an optimal nesting site owing to favourable ocean
      currents that enhance hatchling survival.

PMID- 22378804
TI  - Bottlenose dolphins exchange signature whistles when meeting at sea.
AB  - The bottlenose dolphin, Tursiops truncatus, is one of very few animals that,
      through vocal learning, can invent novel acoustic signals and copy whistles of
      conspecifics. Furthermore, receivers can extract identity information from the
      invented part of whistles. In captivity, dolphins use such signature whistles
      while separated from the rest of their group. However, little is known about how
      they use them at sea. If signature whistles are the main vehicle to transmit
      identity information, then dolphins should exchange these whistles in contexts
      where groups or individuals join. We used passive acoustic localization during
      focal boat follows to observe signature whistle use in the wild. We found that
      stereotypic whistle exchanges occurred primarily when groups of dolphins met and
      joined at sea. A sequence analysis verified that most of the whistles used during
      joins were signature whistles. Whistle matching or copying was not observed in
      any of the joins. The data show that signature whistle exchanges are a
      significant part of a greeting sequence that allows dolphins to identify
      conspecifics when encountering them in the wild.

PMID- 22378805
TI  - Insights into the phylogeny of systematically controversial haptorian ciliates
      (Ciliophora, Litostomatea) based on multigene analyses.
AB  - The ciliate subclass Haptoria is a diverse taxon that includes most of the free
      living predators in the class Litostomatea. Phylogenetic study of this group was
      initially conducted using a single molecular marker small-subunit ribosomal RNA
      (SSU rRNA genes). Multi-gene analysis has been limited because very few other
      sequences were available. We performed phylogenetic analyses of Haptoria
      incorporating new SSU rRNA gene sequences from several debated members of the
      taxon, in particular, the first molecular data from Cyclotrichium. We also
      provided nine large-subunit ribosomal RNA (LSU rRNA) gene sequences and 10 alpha
      tubulin sequences from diverse haptorians, and two possible relatives of
      controversial haptorians (Plagiopylea, Prostomatea). Phylogenies inferred from
      the different molecules showed the following: (i) Cyclotrichium and
      Paraspathidium were clearly separated from the haptorids and even from class
      Litostomatea, rejecting their high-level taxonomic assignments based on
      morphology. Both genera branch instead with the classes Plagiopylea, Prostomatea
      and Oligohymenophora. This raises the possibility that the well-known but
      phylogenetically problematic cyclotrichiids Mesodinium and Myrionecta may also
      have affinities here, rather than with litostomes; (ii) the transfer of
      Trachelotractus to Litostomatea is supported, especially by the analyses of SSU
      rRNA and LSU rRNA genes, however, Trachelotractus and Chaenea (more uncertainly)
      generally form the two deepest lineages within litostomes; and (iii) phylogenies
      of the new molecular markers are consistent with SSU rRNA gene information in
      recovering order Pleurostomatida as monophyletic. However, Pleurostomatida
      branches cladistically within order Haptorida, as does subclass Trichostomatia
      (on the basis of SSU rRNA phylogenies). Our results suggest that the class-level
      taxonomy of ciliates is still not resolved, and also that a systematic revision
      of litostomes is required, beginning at high taxonomic levels (taxa currently
      ranked as subclasses and orders).

PMID- 22378806
TI  - Brilliant camouflage: photonic crystals in the diamond weevil, Entimus
      imperialis.
AB  - The neotropical diamond weevil, Entimus imperialis, is marked by rows of
      brilliant spots on the overall black elytra. The spots are concave pits with
      intricate patterns of structural-coloured scales, consisting of large domains of
      three-dimensional photonic crystals that have a diamond-type structure.
      Reflectance spectra measured from individual scale domains perfectly match model
      spectra, calculated with anatomical data and finite-difference time-domain
      methods. The reflections of single domains are extremely directional (observed
      with a point source less than 5 degrees ), but the special arrangement of the
      scales in the concave pits significantly broadens the angular distribution of the
      reflections. The resulting virtually angle-independent green coloration of the
      weevil closely approximates the colour of a foliaceous background. While the
      close-distance colourful shininess of E. imperialis may facilitate intersexual
      recognition, the diffuse green reflectance of the elytra when seen at long
      distance provides cryptic camouflage.

PMID- 22378807
TI  - Conserved properties of Drosophila and human spermatozoal mRNA repertoires.
AB  - It is now well established that mature mammalian spermatozoa carry a population
      of mRNA molecules, at least some of which are transferred to the oocyte at
      fertilization, however, their function remains largely unclear. To shed light on
      the evolutionary conservation of this feature of sperm biology, we analysed
      highly purified populations of mature sperm from the fruitfly, Drosophila
      melanogaster. As with mammalian sperm, we found a consistently enriched
      population of mRNA molecules that are unlikely to be derived from contaminating
      somatic cells or immature sperm. Using tagged transcripts for three of the
      spermatozoal mRNAs, we demonstrate that they are transferred to the oocyte at
      fertilization and can be detected before, and at least until, the onset of
      zygotic gene expression. We find a remarkable conservation in the functional
      annotations associated with fly and human spermatozoal mRNAs, in particular, a
      highly significant enrichment for transcripts encoding ribosomal proteins (RPs).
      The substantial functional coherence of spermatozoal transcripts in humans and
      the fly opens the possibility of using the power of Drosophila genetics to
      address the function of this enigmatic class of molecules in sperm and in the
      oocyte following fertilization.

PMID- 22378808
TI  - Projected poleward shift of king penguins' (Aptenodytes patagonicus) foraging
      range at the Crozet Islands, southern Indian Ocean.
AB  - Seabird populations of the Southern Ocean have been responding to climate change
      for the last three decades and demographic models suggest that projected warming
      will cause dramatic population changes over the next century. Shift in species
      distribution is likely to be one of the major possible adaptations to changing
      environmental conditions. Habitat models based on a unique long-term tracking
      dataset of king penguin (Aptenodytes patagonicus) breeding on the Crozet Islands
      (southern Indian Ocean) revealed that despite a significant influence of primary
      productivity and mesoscale activity, sea surface temperature consistently drove
      penguins' foraging distribution. According to climate models of the
      Intergovernmental Panel on Climate Change (IPCC), the projected warming of
      surface waters would lead to a gradual southward shift of the more profitable
      foraging zones, ranging from 25 km per decade for the B1 IPCC scenario to 40 km
      per decade for the A1B and A2 scenarios. As a consequence, distances travelled by
      incubating and brooding birds to reach optimal foraging zones associated with the
      polar front would double by 2100. Such a shift is far beyond the usual foraging
      range of king penguins breeding and would negatively affect the Crozet population
      on the long term, unless penguins develop alternative foraging strategies.

PMID- 22378809
TI  - Intragenomic conflict over queen determination favours genomic imprinting in
      eusocial Hymenoptera.
AB  - Colonies of eusocial Hymenoptera, such as ants, bees and wasps, have long been
      recognized as candidates for the study of genomic imprinting on the grounds of
      evolutionary conflicts that arise from close interactions among colony members
      and relatedness asymmetry owing to haplodiploidy. Although a general kinship
      theory of genomic imprinting predicts its occurrence under various circumstances
      of the colony life cycle, new theoretical approaches are required to account for
      the specifics of real colonies based on recent advances in molecular-level
      understanding of ants and honeybees. Using a multivariate quantitative genetic
      model, we examined the potential impact of genomic imprinting on genes that
      determine the carrier female's propensity to develop into the queen caste. When
      queen overproduction owing to the increased propensity comes at a colony-level
      cost, the conflict between maternally and paternally inherited genes in
      polyandrous (queen multiple mating) colonies favours genomic imprinting.
      Moreover, we show that the genomic imprinting can occur even under monandry
      (queen single mating), once incorporating the costs differentially experienced by
      new males and new queens. Our model predicts the existence of imprinted 'genetic
      royal cheats' with patriline-specific expression in polyandrous colonies, and
      seems consistent with the paternal effect on queen determination in monandrous
      Argentine ants.

PMID- 22378810
TI  - Silybum marianum (milk thistle) in the management and prevention of
      hepatotoxicity in a patient undergoing reinduction therapy for acute myelogenous
      leukemia.
AB  - Hepatotoxicity has been observed with several chemotherapy agents and combination
      regimens. Conventional treatment methods often include supportive care or
      observation. We report a case of a patient with noted transaminitis presumed
      secondary to chemotherapy, which did not resolve with supportive care but was
      shown to respond to milk thistle. The patient had an immediate decrease in liver
      function tests and showed decreased elevation in levels upon treatment with
      subsequent chemotherapy regimens. This case demonstrates the potential efficacy
      of milk thistle as a unique hepatoprotective agent.

PMID- 22378811
TI  - Telepharmacy in a rural Alberta Community Cancer Network.
AB  - Telepharmacy services were developed and adopted to compensate for the absence of
      a pharmacist in rural Cancer Centers. Preparation included the formation of an
      advisory committee, development of a training and certification process,
      establishing new policies and operating procedures, collecting utilization data
      and a survey of patient and user satisfaction. Pharmacy technicians at two remote
      community cancer centers were connected by telehealth with pharmacists at one of
      the two coordinating centers to oversee the compounding of intravenous (I.V.)
      chemotherapy and provide clinical review of physician orders. In 8 months of
      telepharmacy use, 247 intravenous preparations were compounded for 47 cancer
      patients during 109 treatment visits. Approximately 45,000 km (27,000 miles) of
      patient travel were averted. Pharmacy staff estimates requires an average of 10
      additional minutes to process and compound each chemotherapy preparation. Nurses
      estimate an average of 27.5 additional minutes required to coordinate information
      for each patient order.

PMID- 22378812
TI  - Sixty years after Hench--corticosteroids and chronic inflammatory disease.
AB  - CONTEXT: Proinflammatory cytokines activate the hypothalamic pituitary adrenal
      axis in the acute phase but not with chronic inflammation; indeed, the
      hypothalamic pituitary adrenal axis is subtly subnormal, with apparently low ACTH
      and cortisol secretion. This paper reviews evidence that suggests that this is
      not simply an adaptation to chronic stress. These patients have increased
      conversion of inactive cortisone (E) to cortisol (F) by 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1). Expression of this enzyme is markedly
      enhanced by TNF, an important autocrine protective mechanism at the inflammatory
      site. EVIDENCE ACQUISITION AND SYNTHESIS: This report reviews the current
      understanding of the interaction between TNF and 11beta-HSD1 in patients with
      chronic inflammatory disease. It is based on publications from PubMed and the
      Science Citation Index. CONCLUSIONS: The systemic effects of enhancing 11beta
      HSD1 activity may amplify the inflammatory response. Thus, increased conversion
      of cortisone to cortisol can alter the circadian rhythm of cortisol secretion
      (lower nadir, later rise, impaired stress response) with consequent relative
      nocturnal cortisol deficiency when inflammatory cytokines are highest. This could
      contribute to the circadian symptomatology in rheumatoid arthritis, the
      effectiveness of early morning (0200 h) low-dose corticosteroids, the significant
      correlation between total body 11beta-HSD1 activity and erythrocyte sedimentation
      rate, and the effectiveness of 11beta-HSD inhibition in both the prevention and
      treatment of adjuvant arthritis in rat models of rheumatoid arthritis. It could
      also explain why anti-TNF therapy benefit can be predicted on the basis of the
      pretreatment plasma cortisol and the subsequent cortisol rise. In contrast, this
      mechanism is likely to be beneficial in the body's response to chronic infections
      such as tuberculosis and could explain why anti-TNF treatment markedly increases
      the risk of reactivation of the disease.

PMID- 22378813
TI  - Risk of rash in cancer patients treated with vandetanib: systematic review and
      meta-analysis.
AB  - BACKGROUND: Vandetanib is an oral inhibitor of vascular endothelial growth factor
      receptor, epidermal growth factor receptor, and rearranged during transfection
      tyrosine kinases. It is approved for the treatment of unresectable or metastatic
      medullary thyroid cancer. Its use may be hindered due to adverse events,
      including rash. The reported incidence and risk of rash to vandetanib varies
      widely and has not been more closely investigated. Therefore, we conducted a
      systematic review and meta-analysis of the literature to determine the incidence
      and risk of developing a rash. DATA SOURCES: Databases from PubMed from 1996
      through July 2011 and abstracts presented at the American Society of Clinical
      Oncology annual meetings from 2004 through July 2011 were searched for relevant
      studies. STUDY SELECTION: Eligible studies were prospective trials that described
      side effects of all-grade or high-grade rash for patients who received vandetanib
      300 mg as a single agent. The incidence of all-grade and high-grade rash and
      relative risk were calculated using random-effects or fixed-effects models.
      RESULTS: Of 63 studies initially identified, nine met the selection criteria and
      were included for the study. A total of 2961 patients were included for analysis.
      The summary incidences of all-grade and high-grade rash were 46.1% [95%
      confidence interval (CI), 40.6-51.8%] and 3.5% (95% CI, 2.5-4.7%), respectively.
      From randomized controlled trials, patients who received vandetanib 300 mg had a
      significantly increased risk of developing all-grade rash in comparison with
      controls, with a relative risk of 2.43 (95% CI, 1.37-4.29; P = 0.002).
      CONCLUSION: There is a significant risk of developing rash in cancer patients
      receiving vandetanib. Awareness and treatment of this adverse event is critical
      to ensure adherence and maximize dosing, guaranteeing the best possible clinical
      benefit.

PMID- 22378814
TI  - A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and
      autosomal dominant pseudohypoparathyroidism type Ib.
AB  - BACKGROUND: Patients with pseudohypoparathyroidism type Ib (PHP-1b) develop
      resistance toward PTH, leading to hypocalcemia and hyperphosphatemia. PHP-1b is
      an imprinted human disorder associated with methylation changes at one or several
      differentially methylated regions at the GNAS locus. This complex locus gives
      rise to several different transcripts with different patterns of imprinted
      expression depending on promoter methylation. They can be either coding [Galphas,
      XLalphas, and neuroendocrine secretory protein-55 (NESP55)] or nontranslated (A/B
      and AS). The paternal AS transcript lies antisense to nesp55. OBJECTIVE: Define
      the genetic defect in a new family with three patients presenting autosomal
      dominant PHP-1b. DESIGN: We used methylation analysis, comparative genomic
      hybridization, and genotyping to characterize the defect. AS expression was
      studied in two patients and their unaffected mothers. RESULTS: A novel deletion
      of 18,988 bp that removes NESP55 and a large part of its counterpart GNAS AS
      intron 4 was discovered. On maternal transmission, this deletion causes loss of
      A/B methylation without affecting XL/AS imprint. On paternal transmission, there
      are no methylation anomalies. The deletion creates a cryptic exon contained
      within AS intron 4, which is expressed from the mutated allele, be it paternal or
      maternal. CONCLUSION: This new deletion suggests that NESP55 is an additional
      imprinting control region that directs A/B methylation in humans. We bring
      arguments in support of the theory of reciprocal inhibition between the
      expression of NESP and AS. However, determining whether loss of methylation at
      the A/B differentially methylated region is a consequence of the loss of NESP
      expression or of the expression of AS requires additional investigations.

PMID- 22378815
TI  - Anti-mullerian hormone as a predictor of time to menopause in late reproductive
      age women.
AB  - CONTEXT: Anti-mullerian hormone (AMH) has emerged as a marker of ovarian reserve
      and a possible surrogate measure of reproductive aging. OBJECTIVE: The aim of the
      study was to evaluate the predictive value of AMH levels in determining the
      median time to menopause for late reproductive age women and the predictive
      ability of AMH compared to FSH and inhibin b. DESIGN AND SETTING: A 14-yr follow
      up in the Penn Ovarian Aging Study, 1996-2010, was conducted for a randomly
      identified population-based cohort. SUBJECTS: A total of 401 late reproductive
      age women participated in the study. MAIN OUTCOME MEASURE: Observed time to
      menopause was measured. RESULTS: All participants were premenopausal, with a mean
      (SD) age of 41.47 (3.52) yr and a median AMH level of 0.68 ng/ml at baseline. AMH
      strongly predicted time to menopause; age further improved predictions. Among
      women with a baseline AMH level below 0.20 ng/ml, the median time to menopause
      was 5.99 yr [95% confidence interval (CI), 4.20-6.33] in the 45- to 48-yr age
      group and 9.94 yr (95% CI, 3.31-12.73) in the 35- to 39-yr age group. With higher
      baseline AMH levels above 1.50 ng/ml, the median time to menopause was 6.23 yr in
      the oldest age group and more than 13.01 yr in the youngest age group. Smoking
      significantly reduced the time to menopause (hazard ratio, 1.61; 95% CI, 1.19
      2.19; P = 0.002). AMH was a stronger predictor of time to menopause than FSH or
      inhibin b. CONCLUSIONS: AMH is a strong predictor of median time to menopause in
      late reproductive age women. Age and smoking are significant and independent
      contributors to the predictions of AMH.

PMID- 22378816
TI  - Thyroid dysfunction and fibrin network structure: a mechanism for increased
      thrombotic risk in hyperthyroid individuals.
AB  - CONTEXT: Hyperthyroidism is associated with increased thrombosis risk, and fibrin
      clot structure determines susceptibility to vascular thrombotic events.
      OBJECTIVE: Our objective was to investigate clot formation and lysis in
      hyperthyroidism using observational and interventional studies. DESIGN: Ex vivo
      fibrin clot structure/fibrinolysis and plasma levels of thrombotic/inflammatory
      markers were investigated in hyperthyroid individuals (n = 24) and matched
      controls (n = 19), using turbidimetric assays, ELISA, and confocal and electron
      microscopy. The effects of normalizing thyroid function were analyzed (n = 19)
      and the role of short-term exogenous hyperthyroidism in healthy volunteers
      studied (n = 16). RESULTS: Hyperthyroid subjects displayed higher clot maximum
      absorbance compared with controls (0.41 +/- 0.03 and 0.27 +/- 0.01 arbitrary
      units, respectively; P < 0.01), and longer clot lysis time (518 +/- 23 and 461 +/
      18 sec, respectively; P < 0.05), which correlated with free T(4) levels. Plasma
      levels of fibrinogen and plasminogen activator inhibitor-1 were significantly
      higher in patients compared with controls. Normalizing thyroid function in 19
      subjects was associated with lower maximum absorbance and shorter lysis time,
      accompanied by reduction in fibrinogen, plasminogen activator inhibitor-1, and D
      dimer levels. Complement C3, but not C-reactive protein, levels were higher in
      hyperthyroid subjects compared with controls (0.92 +/- 0.05 and 0.64 +/- 0.03
      g/liter, respectively; P < 0.01), correlated with clot structure parameters, and
      decreased after intervention. Confocal and electron microscopy confirmed more
      compact clots and impaired fibrinolysis during hyperthyroidism. Exogenous
      hyperthyroidism in healthy volunteers had no effect on any of the clot structure
      parameters. CONCLUSIONS: Endogenous hyperthyroidism is associated with more
      compact clots and resistance to fibrinolysis ex vivo, related to the degree of
      hyperthyroidism and C3 plasma levels, and these changes are modulated by
      achieving euthyroidism. Altered clot structure/lysis may be one mechanism for
      increased thrombotic risk in hyperthyroidism.

PMID- 22378818
TI  - Endothelial dysfunction promotes the transition from compensatory renal
      hypertrophy to kidney injury after unilateral nephrectomy in mice.
AB  - Loss of functional nephrons associated with chronic kidney disease induces
      glomerular hyperfiltration and compensatory renal hypertrophy. We hypothesized
      that the endothelial nitric oxide synthase (eNOS) [soluble guanylate cyclase
      (sGC)] protein kinase G (PKG) pathway plays an important role in compensatory
      renal hypertrophy after unilateral nephrectomy. Analysis of mice subjected to
      unilateral nephrectomy showed increases in kidney weight-to-body weight and total
      protein-to-DNA ratios in wild-type but not eNOS knockout (eNOSKO) mice. Serum
      creatinine and blood urea nitrogen increased after nephrectomy in eNOSKO but not
      in wild-type mice. Furthermore, Bay 41-2272, an sGC stimulator, induced
      compensatory renal hypertrophy in eNOSKO mice and rescued renal function. The NO
      donor S-nitrosoglutathione (GSNO) and Bay 41-2272 stimulated PKG activity and
      induced phosphorylation of Akt protein in human proximal tubular cells. GSNO also
      induced phosphorylation of eukaryotic initiation factor 4E-binding protein and
      ribosomal protein S6. Our results highlight the importance of the eNOS-NO-PKG
      pathway in compensatory renal hypertrophy and suggest that reduced eNOS-NO
      bioavailability due to endothelial dysfunction is the underlying mechanism of
      failure of compensatory hypertrophy and acceleration of progressive renal
      dysfunction.

PMID- 22378819
TI  - Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats:
      the role of nitric oxide as a key mediator.
AB  - Atrial natriuretic peptide (ANP) is an important regulator of blood pressure
      (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric
      oxide (NO) production in different tissues involved in BP control. We
      hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously
      hypertensive rats (SHR) and this contributes to the development and/or
      maintenance of high levels of BP. We investigated the effects of ANP on the NO
      system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity
      and expression in response to peptide infusion, the signaling pathways implicated
      in the signaling cascade that activates NOS, and identifying the natriuretic
      peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR
      C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were
      infused with saline (0.05 ml/min) or ANP (0.2 MUg.kg(-1).min(-1)). NOS activity
      and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were
      measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS
      activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B
      blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin
      inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS
      activity, but activation was lower in SHR than in WKY. ANP had no effect on
      expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and
      nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The
      renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors.
      We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through
      G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was
      diminished in kidneys of SHR. The impaired NO system response to ANP in SHR
      participates in the maintenance of high blood pressure.

PMID- 22378821
TI  - Urinary proteins as novel early diagnostic tools in preeclampsia?

PMID- 22378820
TI  - Differential regulation of circulating and renal ACE2 and ACE in hypertensive
      mRen2.Lewis rats with early-onset diabetes.
AB  - We examined the impact of early diabetes on the circulating and kidney renin
      angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive
      rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age
      for 4 wk without insulin replacement. Systolic blood pressures were not increased
      in DB males or females compared with controls (CON). Circulating angiotensin
      converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and
      threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in
      the DB groups. Serum C-reactive protein was elevated in DB females but not DB
      males, and the vascular responses to acetylcholine and estradiol were attenuated
      in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion
      increased to a similar extent in both DB females and males. Glomerular VEGF
      expression also increased to a similar extent in both DB groups. Renal
      inflammation (CD68(+)cells) increased only in DB females although males exhibited
      greater inflammation that was not different with DB. Cortical ACE2 did not change
      in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%,
      P < 0.05) was markedly reduced in the DB females to that in the DB and CON males.
      ACE activity was significantly lower in both female (75%, P < 0.05) and male
      (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were
      unchanged. In conclusion, female mRen2 rats are not protected from vascular
      damage, renal inflammation, and kidney injury in early STZ-induced diabetes
      despite a marked increase in circulating ACE2 and significantly reduced ACE
      within the kidney.

PMID- 22378823
TI  - Bradykinin-evoked scratching responses in complete Freund's adjuvant-inflamed
      skin through activation of B1 receptor.
AB  - Capsaicin, a potent algogen, induces an itch-related behavior in the presence of
      inflammation. In this study, we tested whether bradykinin (BK) can evoke a
      similar response and investigated the potential mechanisms involved in this
      process. Local inflammation was induced by intradermal injection of complete
      Freund's adjuvant (CFA) into the back of the neck, left hind foot or left cheek
      of male C57BL/6J mice. BK was then injected intradermally into the same area on
      indicated days. Four days after CFA inflammation, BK treatment evoked scratching
      responses in a time- and dose-dependent manner. For BK receptor antagonist
      treatment, inflamed-mice were either given an intraperitoneal injection of B(1)
      receptor (B(1)R) or B(2) receptor (B(2)R) antagonist 30 min prior to BK
      administration, or an intradermal co-injection of antagonist and BK into the
      inflamed area. Our results indicate that B(1)R and B(2)R act in an opposite
      fashion during this process, as pretreatment with B(1)R antagonist by
      intraperitoneal injection significantly reduced BK-induced scratching behavior,
      whereas B(2)R antagonist treatment dramatically increased scratching behavior.
      Moreover, combined injection of BK and B(2)R antagonist enhanced BK-induced
      scratching activity in CFA-inflamed mice. In addition, pretreatment or co
      injection with B(2)R antagonist dramatically reduced the pain-related licking
      behavior induced by BK injection. The data suggest that BK-induced scratching
      responses in CFA-inflamed mouse skin occur via activation of B(1)R. Furthermore,
      B(1) and B(2) receptors play different roles in modulating BK-induced itch
      related behavior in CFA-inflamed mice.

PMID- 22378822
TI  - Genetic deficiency of Smad3 protects the kidneys from atrophy and interstitial
      fibrosis in 2K1C hypertension.
AB  - Although the two-kidney, one-clip (2K1C) model is widely used as a model of human
      renovascular hypertension, mechanisms leading to the development of fibrosis and
      atrophy in the cuffed kidney and compensatory hyperplasia in the contralateral
      kidney have not been defined. Based on the well-established role of the
      transforming growth factor (TGF)-beta signaling pathway in renal fibrosis, we
      tested the hypothesis that abrogation of TGF-beta/Smad3 signaling would prevent
      fibrosis in the cuffed kidney. Renal artery stenosis (RAS) was established in
      mice with a targeted disruption of exon 2 of the Smad3 gene (Smad3 KO) and wild
      type (WT) controls by placement of a polytetrafluoroethylene cuff on the right
      renal artery. Serial pulse-wave Doppler ultrasound assessments verified that
      blood flow through the cuffed renal artery was decreased to a similar extent in
      Smad3 KO and WT mice. Two weeks after surgery, systolic blood pressure and plasma
      renin activity were significantly elevated in both the Smad3 KO and WT mice. The
      cuffed kidney of WT mice developed renal atrophy (50% reduction in weight after 6
      wk, P < 0.0001), which was associated with the development of interstitial
      fibrosis, tubular atrophy, and interstitial inflammation. Remarkably, despite a
      similar reduction of renal blood flow, the cuffed kidney of the Smad3 KO mice
      showed minimal atrophy (9% reduction in weight, P = not significant), with no
      significant histopathological alterations (interstitial fibrosis, tubular
      atrophy, and interstitial inflammation). We conclude that abrogation of TGF
      beta/Smad3 signaling confers protection against the development of fibrosis and
      atrophy in RAS.

PMID- 22378824
TI  - Synthesis and secretory expression of hybrid antimicrobial peptide CecA-mag and
      its mutants in Pichia pastoris.
AB  - The hybrid peptide CA(1-7)-M(2-12) gene was designed according to the N-terminal
      1-7 amino acid sequence of the antimicrobial peptide cecropin A (CA) and the N
      terminal 2-12 amino acid sequence of maganin (M) and synthesized using Pichia
      pastoris preferred codons. The gene was cloned into pPICZalphaA and transformed
      into the P. pastoris recipient bacterium SMD1168, regulated by the alcohol
      oxidase (AOX). Expression of the cecA-mag hybrid antimicrobial peptide (MW, 1.9
      kDa) revealed broad-spectrum antibiotic activity and to the ability to inhibit
      growth of most G(-) and G(+) bacteria. Three mutants of cecA-mag were designed
      and synthesized by recombination polymerase chain reaction site-directed
      mutagenesis to investigate the relationship between the structure and function of
      this antimicrobial peptide. The inhibition titers of these mutants against
      Staphylococcus aureus were evaluated using the agar diffusion method. Under the
      conditions of the same concentration and volume, the bacteriostatic diameters of
      three cecA-mag mutants were 1.2, 1.2 and 1.5 times, respectively, compared with
      the diameters of wild-type cecA-mag.

PMID- 22378825
TI  - Fetal ethanol exposure attenuates aversive oral effects of TrpV1, but not TrpA1
      agonists in rats.
AB  - In humans, fetal ethanol exposure is highly predictive of adolescent ethanol use
      and abuse. Prior work in our labs indicated that fetal ethanol exposure results
      in stimulus-induced chemosensory plasticity in the taste and olfactory systems of
      adolescent rats. In particular, we found that increased ethanol acceptability
      could be attributed, in part, to an attenuated aversion to ethanol's aversive
      odor and quinine-like bitter taste quality. Here, we asked whether fetal ethanol
      exposure also alters the oral trigeminal response of adolescent rats to ethanol.
      We focused on two excitatory ligand-gated ion channels, TrpV1 and TrpA1, which
      are expressed in oral trigeminal neurons and mediate the aversive orosensory
      response to many chemical irritants. To target TrpV1, we used capsaicin, and to
      target TrpA1, we used allyl isothiocyanate (or mustard oil). We assessed the
      aversive oral effects of ethanol, together with capsaicin and mustard oil, by
      measuring short-term licking responses to a range of concentrations of each
      chemical. Experimental rats were exposed in utero by administering ethanol to
      dams through a liquid diet. Control rats had ad libitum access to an iso-caloric
      iso-nutritive liquid diet. We found that fetal ethanol exposure attenuated the
      oral aversiveness of ethanol and capsaicin, but not mustard oil, in adolescent
      rats. Moreover, the increased acceptability of ethanol was directly related to
      the reduced aversiveness of the TrpV1-mediated orosensory input. We propose that
      fetal ethanol exposure increases ethanol avidity not only by making ethanol smell
      and taste better, but also by attenuating ethanol's capsaicin-like burning
      sensations.

PMID- 22378826
TI  - Metastatic neuroblastoma presenting as recurrent facial paralysis.

PMID- 22378827
TI  - Utility outcome assessment of the aging neck following massive weight loss.
AB  - OBJECTIVE: The authors set out to quantify the health state utility assessment of
      living with the physical appearance of the aging neck following massive weight
      loss. Described utility scores may help to establish the health burden of the
      aging neck in the growing bariatric patient population. STUDY DESIGN: Prospective
      cohort observational study. SETTING: Tertiary referral medical center. SUBJECTS
      AND METHODS: Three validated tools were used to determine utility scores for
      living with an aging neck: visual analog scale (VAS), time trade-off (TTO), and
      standard gamble (SG). A 5-point Likert scale was used to evaluate the subjects'
      ease of understanding. A prospective sample of volunteers from the general
      population and medical students was used for this assessment. RESULTS: In total,
      118 prospective volunteers were included in the survey. All measures (VAS, TTO,
      SG); (0.89 +/- 0.07, 0.94 +/- 0.08, and 0.95 +/- 0.10, respectively) varied (P <
      .0001) from the corresponding ones for monocular blindness (0.62 +/- 0.18, 0.87
      +/- 0.15, and 0.85 +/- 0.20, respectively) and binocular blindness (0.32 +/-
      0.18, 0.66 +/- 0.25, and 0.64 +/- 0.28, respectively). CONCLUSION: The authors
      objectified the health state of living with an aging neck in the massive weight
      loss patient with utility scores (TTO, 0.94) comparable with those living with
      obstructive sleep apnea. This sample population, if faced with an aging neck
      following massive weight loss, would undertake a neck rejuvenation procedure with
      a theoretical 5% chance of mortality and would be willing to trade 2.1 years of
      remaining life-years to attain this procedure.

PMID- 22378828
TI  - Myocardial infarction with normal coronaries: an autopsy perspective.
AB  - AIM: To analyse postmortem cases of myocardial infarction (MI) with normal
      coronary arteries in terms of patient characteristics, features of the MI and
      risk factors. METHODS: This retrospective non-case controlled study was carried
      out at a specialist cardiac pathology department at a tertiary cardiac referral
      centre. Cases of histologically confirmed MI and normal coronary arteries during
      the period 1996-2010 were identified and analysed for the presence of risk
      factors. RESULTS: Nineteen cases of histologically confirmed MI and normal
      coronary arteries were identified with a similar gender ratio 1:1.1 (male:female)
      and mean age of 33 +/- 12 years (range 14-58). All patients died suddenly. The
      location of the infarct was variable, with left anterior descending artery
      territory being the single most prevalent (47%). Risk factors were identified in
      the majority of cases (n=14), with some cases experiencing more than one
      association, including alcohol and/or predominately class A drug use (n=7),
      including cocaine, inflammation (n=2), hypercoagulable state (n=3) and exertion
      (n=2). CONCLUSIONS: Current data regarding prognosis in MI with normal coronary
      arteries suggests a favourable outcome in the context of major cardiovascular
      events. No large series of fatal cases have been reported. This study highlights
      that this entity can be fatal and its prognosis may be less favourable than
      currently considered. This autopsy series also demonstrates that the causation of
      MI with normal coronary arteries is complex and multifactorial, including a
      history of alcohol and/or drug use. It also highlights the importance of accurate
      epidemiological data from referring pathologists.

PMID- 22378829
TI  - Ethnic drinking cultures and alcohol use among Asian American adults: findings
      from a national survey.
AB  - AIMS: To investigate the influence of ethnic drinking cultures on alcohol use by
      Asian Americans and how this influence may be moderated by their level of
      integration into Asian ethnic cultures. METHODS: A nationally representative
      sample of 952 Asian American adults extracted from the Wave 2 National
      Epidemiologic Survey of Alcohol and Related Conditions data was used. Multiple
      logistic and linear regression models were fitted, some of which were stratified
      by nativity. RESULTS: Controlling for financial stress, discrimination and
      demographic variables, a hypothesized, positive relationship between ethnic
      drinking cultures and alcohol outcomes held for most drinking outcomes. A
      hypothesis on the moderating effect of integration into ethnic cultures indicated
      by ethnic language use was supported for US-born Asian Americans. CONCLUSION:
      Ethnic drinking cultures may significantly influence alcohol use by Asian
      Americans. The influence of ethnic drinking cultures may be conditioned by the
      degree of integration into the ethnic cultures. To inform alcohol interventions
      for reducing harmful and hazardous alcohol use among immigrants, future research
      needs to explore the cultural and social processes occurring in immigrant
      communities that might significantly influence drinking.

PMID- 22378830
TI  - Your love lifts me higher! The energizing quality of secure relationships.
AB  - Three studies tested and confirmed the hypothesis that secure attachment
      relationships lead to feelings of security and energy, as well as willingness to
      explore. In Study 1, priming a secure attachment relationship increased felt
      security and energy. In Studies 2 and 3, felt energy mediated the effect of
      (primed) secure attachment relationships on willingness to explore. In Study 3,
      the effect of (primed) secure attachment relationships on felt energy and
      willingness to explore was independent of general positive affect. Secure
      attachments energize partners, thus enabling exploration.

PMID- 22378831
TI  - Bad for me or bad for us? Interpersonal orientations and the impact of losses on
      unethical behavior.
AB  - The present research examines the role of allocations of losses versus gains on
      the emergence of unethical behavior as a function of people's social value
      orientation. The authors demonstrate that (a) proselfs regard unethical behavior
      to prevent losses as more justified than prosocials (Study 1) and (b) proselfs
      engage in more unethical behavior to prevent losses than prosocials (Study 2).
      These differences are explained by prosocials' greater concern for harm to
      interdependent others in the domain of losses. A third study further
      substantiates these findings by revealing that unethical behavior to prevent
      losses increases among prosocials as harm to others is reduced. In sum, these
      results reveal that depending on whether people attend only to their self
      interest or also consider the outcomes of others, losses either may increase or
      curtail unethical conduct. Considering social value orientations thus may
      reconcile conflicting theoretical perspectives on the impact of losses on social
      decisions.

PMID- 22378832
TI  - Microsatellite markers from Ceanothus roderickii (Rhamnaceae) using next
      generation sequencing technology.
AB  - PREMISE OF THE STUDY: Ceanothus roderickii is an endangered shrub endemic to
      California. To investigate the population genetics of this species, including the
      genetic consequences of population fragmentation and hybridization, 10
      microsatellite markers were developed. METHODS AND RESULTS: Using next-generation
      sequencing (454) data from a single C. roderickii individual, 10 microsatellite
      markers were developed. A group of 12 individuals representing all of the major
      C. roderickii populations were analyzed. All loci were found to be polymorphic,
      with a range from two to 12 alleles per locus. Observed heterozygosity ranged
      from 0.08 to 0.83 across loci. All 10 loci were also amplifiable in at least one
      other Ceanothus species. CONCLUSIONS: Results presented here indicate the utility
      of our new microsatellite primers in ongoing and future studies concerning
      population genetics and gene flow in C. roderickii, as well as the potential
      applicability of these primers in similar studies on other Ceanothus species.

PMID- 22378833
TI  - Time-calibrated phylogeny of the woody Australian genus Hakea (Proteaceae)
      supports multiple origins of insect-pollination among bird-pollinated ancestors.
AB  - PREMISE OF THE STUDY: A past study based on morphological data alone showed that
      the means by which plants of the Australian genus Hakea reduce florivory is
      related to the evolution of bird pollination. For example, bird pollination was
      shown to have arisen only in insect-pollinated lineages that already produced
      greater amounts of floral cyanide, a feature that reduces florivory. We examine a
      central conclusion of that study, and a common assumption in the literature, that
      bird pollination arose in insect-pollinated lineages, rather than the reverse.
      METHODS: We combined morphological and DNA data to infer the phylogeny and age of
      the Australian genus Hakea, using 9.2 kilobases of plastid and nuclear DNA and 46
      morphological characters from a taxonomically even sampling of 55 of the 149
      species. KEY RESULTS: Hakea is rooted confidently in a position that has not been
      suggested before. The phylogeny implies that bird pollination is primitive in
      Hakea and that multiple shifts to insect pollination have occurred. The
      unexpectedly young age of Hakea (a crown age of ca. 10 Ma) makes it coincident
      with its primary bird pollinators (honeyeaters) throughout its history.
      CONCLUSIONS: Our study demonstrates that Hakea is an exception to the more
      commonly described shift from insect to bird pollination. However, we note that
      only one previous phylogenetic study involved Australian plants and their
      honeyeater pollinators and that our finding might prove to be more common on that
      continent.

PMID- 22378834
TI  - Intralesional injection of pingyangmycin is a safe and effective treatment for
      microcystic lymphatic malformations in the tongue.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intralesional injection of
      pingyangmycin for the treatment of microcystic lymphatic malformations (LMs) in
      the tongue. METHODS: Eighteen patients with tongue microcystic LMs were treated
      with intralesional injection of pingyangmycin. The concentration of the drug was
      1 mg/mL with an addition of dexamethasone. Repeated injections were performed at
      an interval of 3-4 weeks. The results were evaluated by clinical examinations and
      Doppler ultrasonography scan. The follow-up period was 12 months to eight years
      after the last treatment and the mean follow-up time was three years. All
      patients received 1-8 injections (mean, 3.0 injections) for the whole course of
      treatment. The total dose of pingyangmycin administered was 8-64 mg (mean, 24
      mg). RESULTS: Fifteen patients had complete response with no cosmetic or
      functional problems.Three patients with macroglossia had a reduction of 50-90% in
      the lesion size and needed secondary surgery. No serious complications were
      encountered. CONCLUSION: The results suggested that intralesional injection of
      pingyangmycin is an effective and safe treatment for microcystic LMs in the
      tongue, and can be used as the first-line treatment protocol.

PMID- 22378835
TI  - Maintaining an outward image: a Korean immigrant's life with type 2 diabetes
      mellitus and hypertension.
AB  - Type 2 diabetes mellitus (DM) and hypertension (HTN) disproportionately affect
      minority populations in the United States, including Korean American immigrants
      (KAI). We conducted qualitative interviews with middle-aged KAI in Maryland
      living with DM and HTN to examine the illness experience to inform future
      intervention strategies. Study results show that participants utilized strategies
      to maintain respect and Korean identity, including an image of being healthy and
      in control of their behavior in the public arena. These strategies included the
      lack of disclosure of their illness, even to family members, and avoiding outside
      assistance when engaging in problem solving. Maintaining an outward image of
      health was a common goal that affected the self-care of KAI in this study, a
      finding that might prove significant in the management of other chronic illnesses
      affecting this population. The study findings demonstrate the importance of in
      depth understanding of specific populations when treating chronic illness, and
      caretakers' sensitivity to each population's unique cultural issues regarding
      identity, image, and disclosure.

PMID- 22378836
TI  - Understanding the role of communities of practice in evidence-informed decision
      making in public health.
AB  - In this article we report on qualitative findings that describe public health
      practitioners' practice-based definitions of evidence-informed decision making
      (EIDM) and communities of practice (CoP), and how CoP could be a mechanism to
      enhance their capacity to practice EIDM. Our findings emerged from a qualitative
      descriptive analysis of group discussions and participant concept maps from two
      consensus-building workshops that were conducted with public health practitioners
      (N = 90) in two provinces in eastern Canada. Participants recognized the
      importance of EIDM and the significance of integrating explicit and tacit
      evidence in the EIDM process, which was enhanced by CoP. Tacit knowledge,
      particularly from peers and personal experience, was the preferred source of
      knowledge, with informal peer interactions being the favored form of CoP to
      support EIDM. CoP helped practitioners build relationships and community
      capacity, share and create knowledge, and build professional confidence and
      critical inquiry. Participants described individual and organizational attributes
      that were needed to enable CoP and EIDM.

PMID- 22378837
TI  - Maternal tissue is involved in stimulant reception by seeds of the parasitic
      plant Orobanche.
AB  - BACKGROUND AND AIMS: A fundamental element in the evolution of obligate root
      parasitic angiosperms is their ability to germinate only in response to chemical
      stimulation by roots, to ensure contact with a nearby nourishing host. The aim of
      this study was to explore inheritance of the unique germination control in this
      group of plants. METHODS: Analysis was made of the segregation of spontaneous
      (non-induced) germination that appeared in hybrid progenies derived from crosses
      between Orobanche cernua and O. cumana, which, like all other Orobanche species,
      are totally dependent on chemical stimulation for the onset of germination, and
      show negligible spontaneous germination in their natural seed populations. KEY
      RESULTS AND CONCLUSIONS: F(1) and F(2) seeds did not germinate in the absence of
      chemical stimulation, but significant spontaneous germination was found in some
      F(3) seed families. This indicates that the prevention of non-induced germination
      in Orobanche seeds, i.e. dependence on an external chemical stimulation for seed
      germination, is genetically controlled, that this genetic control is expressed in
      a seed tissue with maternal origin (presumably the perisperm that originates from
      the nucellus) and that genetic variation for this trait exists in Orobanche
      species. Similar segregation results were obtained in reciprocal crosses,
      suggesting that stimulated germination is controlled by nuclear genes.

PMID- 22378838
TI  - Is genetic engineering ever going to take off in forage, turf and bioenergy crop
      breeding?
AB  - BACKGROUND: Genetic engineering offers the opportunity to generate unique genetic
      variation that is either absent in the sexually compatible gene pool or has very
      low heritability. The generation of transgenic plants, coupled with breeding, has
      led to the production of widely used transgenic cultivars in several major cash
      crops, such as maize, soybean, cotton and canola. The process for regulatory
      approval of genetically engineered crops is slow and subject to extensive
      political interference. The situation in forage grasses and legumes is more
      complicated. SCOPE: Most widely grown forage, turf and bioenergy species (e.g.
      tall fescue, perennial ryegrass, switchgrass, alfalfa, white clover) are highly
      self-incompatible and outcrossing. Compared with inbreeding species, they have a
      high potential to pass their genes to adjacent plants. A major biosafety concern
      in these species is pollen-mediated transgene flow. Because human consumption is
      indirect, risk assessment of transgenic forage, turf and bioenergy species has
      focused on their environmental or ecological impacts. Although significant
      progress has been made in genetic modification of these species,
      commercialization of transgenic cultivars is very limited because of the
      stringent and costly regulatory requirements. To date, the only transgenic forage
      crop deregulated in the US is 'Roundup Ready' (RR) alfalfa. The approval process
      for RR alfalfa was complicated, involving several rounds of regulation,
      deregulation and re-regulation. Nevertheless, commercialization of RR alfalfa is
      an important step forward in regulatory approval of a perennial outcrossing
      forage crop. As additional transgenic forage, turf and bioenergy crops are
      generated and tested, different strategies have been developed to meet regulatory
      requirements. Recent progress in risk assessment and deregulation of transgenic
      forage and turf species is summarized and discussed.

PMID- 22378839
TI  - Evolution of mixed-linkage (1 -> 3, 1 -> 4)-beta-D-glucan (MLG) and xyloglucan in
      Equisetum (horsetails) and other monilophytes.
AB  - BACKGROUND AND AIMS: Horsetails (Equisetopsida) diverged from other extant
      eusporangiate monilophytes in the Upper Palaeozoic. They are the only
      monilophytes known to contain the hemicellulose mixed-linkage (1 -> 3, 1 -> 4)
      beta-d-glucan (MLG), whereas all land plants possess xyloglucan. It has been
      reported that changes in cell-wall chemistry often accompanied major evolutionary
      steps. We explored changes in hemicelluloses occurring during Equisetum
      evolution. METHODS: Hemicellulose from numerous monilophytes was treated with
      lichenase and xyloglucan endoglucanase. Lichenase digests MLG to di-, tri- and
      tetrasaccharide repeat-units, resolvable by thin-layer chromatography. KEY
      RESULTS: Among monilophytes, MLG was confined to horsetails. Our analyses support
      a basal trichotomy of extant horsetails: MLG was more abundant in subgenus
      Equisetum than in subgenus Hippochaete, and uniquely the sister group E.
      bogotense yielded almost solely the tetrasaccharide repeat-unit (G4G4G3G). Other
      species also gave the disaccharide, whereas the trisaccharide was consistently
      very scarce. Tetrasaccharide : disaccharide ratios varied interspecifically, but
      with no consistent difference between subgenera. Xyloglucan was scarce in
      Psilotum and subgenus Equisetum, but abundant in subgenus Hippochaete and in the
      eusporangiate ferns Marattia and Angiopteris; leptosporangiate ferns varied
      widely. All monilophytes shared a core pattern of xyloglucan repeat-units, major
      XEG products co-chromatographing on thin-layer chromatography with non
      fucosylated hepta-, octa- and nonasaccharides and fucose-containing nona- and
      decasaccharides. CONCLUSIONS: G4G4G3G is the ancestral repeat-unit of horsetail
      MLG. Horsetail evolution was accompanied by quantitative and qualitative
      modification of MLG; variation within subgenus Hippochaete suggests that the
      structure and biosynthesis of MLG is evolutionarily plastic. Xyloglucan quantity
      correlates negatively with abundance of other hemicelluloses; but qualitatively,
      all monilophyte xyloglucans conform to a core pattern of repeat-unit sizes.

PMID- 22378840
TI  - Mechanisms of cervical spine injury in rugby union: a systematic review of the
      literature.
AB  - BACKGROUND: Severe cervical spine injury in rugby union (rugby) exerts a major
      impact on the individual who sustains the injury and on the broader society.
      Since the late 1970s, authors of rugby case report studies have postulated that
      the underlying mechanism of cervical spine injury is hyperflexion of the neck.
      However, this is in conflict with findings from more recent experimental studies.
      These have shown that it is more likely that the majority of cervical spine
      injuries occur due to buckling of the cervical spinal column. OBJECTIVE: To
      investigate the primary mechanism of cervical spine injury in rugby. METHODS: A
      comprehensive and systematic review of the literature was undertaken. Six key
      factors were identified and subsequently used to investigate the two principally
      postulated mechanisms of cervical spine injury: hyperflexion and buckling.
      RESULTS: Facet dislocations, in particular bilateral facet dislocations, were
      identified as the most common types of cervical spine injury in rugby. Trauma
      occurred most often at lower cervical spinal levels, notably the C4/5 and C5/6
      motion segments. Experimental studies demonstrate that bilateral facet
      dislocations occurring at the lower cervical spinal levels are primarily produced
      via buckling. CONCLUSION: Our analysis of key factors for cervical spine injury
      in rugby shows that it is unlikely that the majority of injuries occur after
      hyperflexion of the neck. It appears more likely that they are the result of
      buckling of the cervical spinal column.

PMID- 22378842
TI  - Estimating the extent and distribution of new-onset adult asthma in British
      Columbia using frequentist and Bayesian approaches.
AB  - INTRODUCTION: We previously described a method to identify the incidence of new
      onset adult asthma (NOAA) in Alberta by industry and occupation, utilizing
      Workers' Compensation Board (WCB) and physician billing data. The aim of this
      study was to extend this method to data from British Columbia (BC) so as to
      compare the two provinces and to incorporate Bayesian methodology into estimates
      of risk. METHODS: WCB claims for any reason 1995-2004 were linked to physician
      billing data. NOAA was defined as a billing for asthma (ICD-9 493) in the 12
      months before a WCB claim without asthma in the previous 3 years. Incidence was
      calculated by occupation and industry. In a matched case-referent analysis,
      associations with exposures were examined using an asthma-specific job exposure
      matrix (JEM). Posterior distributions from the Alberta analysis and estimated
      misclassification parameters were used as priors in the Bayesian analysis of the
      BC data. RESULTS: Among 1 118 239 eligible WCB claims the incidence of NOAA was
      1.4%. Sixteen occupations and 44 industries had a significantly increased risk;
      six industries had a decreased risk. The JEM identified wood dust [odds ratio
      (OR) 1.55, 95% confidence interval (CI) 1.08-2.24] and animal antigens (OR 1.66,
      95% CI 1.17-2.36) as related to an increased risk of NOAA. Exposure to
      isocyanates was associated with decreased risk (OR 0.57, 95% CI 0.39-0.85).
      Bayesian analyses taking account of exposure misclassification and informative
      priors resulted in posterior distributions of ORs with lower boundary of 95%
      credible intervals >1.00 for almost all exposures. CONCLUSIONS: The distribution
      of NOAA in BC appeared somewhat similar to that in Alberta, except for
      isocyanates. Bayesian analyses allowed incorporation of prior evidence into risk
      estimates, permitting reconsideration of the apparently protective effect of
      isocyanate exposure.

PMID- 22378843
TI  - Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell
      line.
AB  - Silica mesoporous nanoparticles have been recently selected for a wide range of
      applications from electronics to medicine due to their intrinsic properties.
      Among medical applications, drug delivery using SiO(2) nanoparticles by oral
      route is under study. Major benefits are expected including higher specificity
      and sensitivity together with side effect reduction. Since literature shows that
      very complex and unexpected interactions could occur between nanomaterials and
      biological systems, one critical issue is to control the nanoparticle
      cytotoxicity/genotoxicity for normal tissues and specially stomach and intestine
      when oral route is considered. The aim of the work is to study the cytotoxicity
      and genotoxicity of SiO(2) nanoparticles on HT29 human intestine cell line, using
      conventional and innovative methodologies, for measuring cell viability and
      proliferation, global metabolism, genotoxicity, and nanoparticles uptake. Core
      dye doped SiO(2) nanoparticles of 25 and 100 nm were specifically synthesized to
      track nanoparticles incorporation by confocal and video microscopy. Besides
      conventional approaches (sulforhodamine B, flow cytometry, and gamma-H2Ax foci),
      we have performed a real-time monitoring of cell proliferation using an impedance
      based system which ensure no interference between measures and nanoparticles
      physicochemical characteristics. Overall, our results showed that SiO(2)-25nm and
      SiO(2)-100nm induced a rather limited cytotoxic and genotoxic effects on HT-29
      cells after a 24 h exposure. However, regarding cell viability and genotoxicity,
      inverse dose-dependent relationships were observed for SiO(2)-100nm
      nanoparticles. In conclusion, it seems that the higher the dose of SiO(2)-100nm,
      the lower the cytotoxic/genotoxic effects, data that well illustrate the
      complexity in identifying and understanding the hazards of nanoparticles for
      human health.

PMID- 22378844
TI  - miR-155 regulates IFN-gamma production in natural killer cells.
AB  - MicroRNAs (miRs) are small, noncoding RNA molecules with important regulatory
      functions whose role in regulating natural killer (NK) cell biology is not well
      defined. Here, we show that miR-155 is synergistically induced in primary human
      NK cells after costimulation with IL-12 and IL-18, or with IL-12 and CD16
      clustering. Over-expression of miR-155 enhanced induction of IFN-gamma by IL-12
      and IL-18 or CD16 stimulation, whereas knockdown of miR-155 or its disruption
      suppressed IFN-gamma induction in monokine and/or CD16-stimulated NK cells. These
      effects on the regulation of NK cell IFN-gamma expression were found to be
      mediated at least in part via miR-155's direct effects on the inositol
      phosphatase SHIP1. Consistent with this, we observed that modulation of miR-155
      overrides IL-12 and IL-18-mediated regulation of SHIP1 expression in NK cells.
      Collectively, our data indicate that miR-155 expression is regulated by stimuli
      that strongly induce IFN-gamma in NK cells such as IL-12, IL-18, and CD16
      activation, and that miR-155 functions as a positive regulator of IFN-gamma
      production in human NK cells, at least in part via down-regulating SHIP1. These
      findings may have clinical relevance for targeting miR-155 in neoplastic disease.

PMID- 22378845
TI  - Thrombopoietin receptor down-modulation by JAK2 V617F: restoration of receptor
      levels by inhibitors of pathologic JAK2 signaling and of proteasomes.
AB  - The constitutively active JAK2 V617F mutant is the major determinant of human
      myeloproliferative neoplasms (MPNs). We show that coexpression of murine JAK2
      V617F and the murine thrombopoietin (Tpo) receptor (TpoR, c-MPL) in hematopoietic
      cell lines or heterozygous knock-in of JAK2 V617F in mice leads to down
      modulation of TpoR levels. Enhanced TpoR ubiquitinylation, proteasomal
      degradation, reduced recycling, and maturation are induced by the constitutive
      JAK2 V617F activity. These effects can be prevented in cell lines by JAK2 and
      proteasome inhibitors. Restoration of TpoR levels by inhibitors could be detected
      in platelets from JAK2 inhibitor-treated myelofibrosis patients that express the
      JAK2 V617F mutant, and in platelets from JAK2 V617F knock-in mice that were
      treated in vivo with JAK2 or proteasome inhibitors. In addition, we show that Tpo
      can induce both proliferative and antiproliferative effects via TpoR at low and
      high JAK2 activation levels, respectively, or on expression of JAK2 V617F. The
      antiproliferative signaling and receptor down-modulation by JAK2 V617F were
      dependent on signaling via TpoR cytosolic tyrosine 626. We propose that selection
      against TpoR antiproliferative signaling occurs by TpoR down-modulation and that
      restoration of down-modulated TpoR levels could become a biomarker for the
      treatment of MPNs.

PMID- 22378846
TI  - The hypersensitive sites of the murine beta-globin locus control region act
      independently to affect nuclear localization and transcriptional elongation.
AB  - The beta-globin locus control region (LCR) is necessary for high-level beta
      globin gene transcription and differentiation-dependent relocation of the beta
      globin locus from the nuclear periphery to the central nucleoplasm and to foci of
      hyperphosphorylated Pol II "transcription factories" (TFys). To determine the
      contribution of individual LCR DNaseI hypersensitive sites (HSs) to transcription
      and nuclear location, in the present study, we compared beta-globin gene activity
      and location in erythroid cells derived from mice with deletions of individual
      HSs, deletions of 2 HSs, and deletion of the whole LCR and found all of the HSs
      had a similar spectrum of activities, albeit to different degrees. Each HS acts
      as an independent module to activate expression in an additive manner, and this
      is correlated with relocation away from the nuclear periphery. In contrast, HSs
      have redundant activities with respect to association with TFys and the
      probability that an allele is actively transcribed, as measured by primary RNA
      transcript FISH. The limiting effect on RNA levels occurs after beta-globin genes
      associate with TFys, at which time HSs contribute to the amount of RNA arising
      from each burst of transcription by stimulating transcriptional elongation.

PMID- 22378847
TI  - p85beta regulatory subunit of class IA PI3 kinase negatively regulates mast cell
      growth, maturation, and leukemogenesis.
AB  - We show that loss of p85alpha inhibits the growth and maturation of mast cells,
      whereas loss of p85beta enhances this process. Whereas restoring the expression
      of p85alpha in P85alpha(-/-) cells restores these functions, overexpression of
      p85beta has the opposite effect. Consistently, overexpression of p85beta in WT
      mast cells represses KIT-induced proliferation and IL-3-mediated maturation by
      inhibiting the expression of Microphthalmia transcription factor. Because
      p85alpha and p85beta differ in their N-terminal sequences, chimeric proteins
      consisting of amino or carboxy-terminal of p85alpha and/or p85beta do not rescue
      the growth defects of p85alpha(-/-) cells, suggesting cooperation between these
      domains for normal mast cell function. Loss of p85beta impaired ligand induced
      KIT receptor internalization and its overexpression enhanced this process, partly
      because of increased binding of c-Cbl to p85beta relative to p85alpha. In vivo,
      loss of p85beta resulted in increased mast cells, and bone marrow transplantation
      of cells overexpressing p85beta resulted in significant reduction in some tissue
      mast cells. Overexpression of p85beta suppressed the growth of oncogenic KIT
      expressing cells in vitro and prolonged the survival of leukemic mice in vivo.
      Thus, p85alpha and p85beta differentially regulate SCF and oncogenic KIT-induced
      signals in myeloid lineage-derived mast cells.

PMID- 22378849
TI  - Pulmonary atresia with intact ventricular septum: how good is a biventricular
      repair?

PMID- 22378850
TI  - Predicting prognosis in cardiac surgery: a prophecy?

PMID- 22378848
TI  - Correlation of CD33 expression level with disease characteristics and response to
      gemtuzumab ozogamicin containing chemotherapy in childhood AML.
AB  - CD33 is expressed on the majority of acute myeloid leukemia (AML) leukemic blasts
      and is the target for gemtuzumab ozogamicin (GO), a toxin-conjugated anti-CD33
      mAb. In the present study, we quantified the CD33 mean fluorescent intensity of
      leukemic blasts prospectively in 619 de novo pediatric AML patients enrolled in
      Children's Oncology Group GO-containing clinical trials and determined its
      correlation with disease characteristics and clinical outcome. CD33 expression
      varied more than 2-log fold; a median mean fluorescent intensity of 129 (range, 3
      1550.07) was observed. Patients were divided into 4 quartiles, quartiles 1-4 (Q1
      4) based on expression and disease characteristics and clinical response defined
      across quartiles. High CD33 expression was associated with high-risk FLT3/ITD
      mutations (P < .001) and was inversely associated with low-risk disease (P <
      .001). Complete remission (CR) rates were similar, but patients in Q4 had
      significantly lower overall survival (57% +/- 16% vs 77% +/- 7%, P = .002) and
      disease-free survival from CR (44% +/- 16% vs 62% +/- 8%, P = .022). In a
      multivariate model, high CD33 expression remained a significant predictor of
      overall survival (P = .011) and disease-free survival (P = .038) from CR. Our
      findings suggest that CD33 expression is heterogeneous within de novo pediatric
      AML. High expression is associated with adverse disease features and is an
      independent predictor of inferior outcome. The correlation between CD33
      expression and GO response is under investigation. These studies are registered
      at www.clinicaltrials.gov as NCT00070174 and NCT00372593.

PMID- 22378851
TI  - EuroSCORE II, illum qui est gravitates magni observe.

PMID- 22378852
TI  - Mechanical unloading and cell therapy have a synergistic role in the recovery and
      regeneration of the failing heart.
AB  - The problem of a growing patient population with end-stage heart failure and a
      fixed cardiac donor pool has stimulated the development of novel therapies for
      heart failure. Two therapeutic strategies have emerged with the potential to
      improve the landscape of the clinical management of heart failure. First, left
      ventricular assist device therapy is able to sustain the circulation of patients
      in end-stage heart failure and may promote cardiac recovery. Secondly, stem cell
      therapy can potentially be used to induce myocardial regeneration replacing lost
      or non-functioning native myocardium. In this review, we present evidence that
      these strategies may overlap significantly in their mechanisms of action at the
      systems, organ, tissue and cellular levels. We review the current clinical
      evidence of their combined use.

PMID- 22378853
TI  - Retained surgical sponge presenting as a cardiac mass.

PMID- 22378854
TI  - The ring around the heart.

PMID- 22378855
TI  - EuroSCORE II.
AB  - OBJECTIVES: To update the European System for Cardiac Operative Risk Evaluation
      (EuroSCORE) risk model. METHODS: A dedicated website collected prospective risk
      and outcome data on 22,381 consecutive patients undergoing major cardiac surgery
      in 154 hospitals in 43 countries over a 12-week period (May-July 2010).
      Completeness and accuracy were validated during data collection using mandatory
      field entry, error and range checks and after data collection using summary
      feedback confirmation by responsible officers and multiple logic checks.
      Information was obtained on existing EuroSCORE risk factors and additional
      factors proven to influence risk from research conducted since the original
      model. The primary outcome was mortality at the base hospital. Secondary outcomes
      were mortality at 30 and 90 days. The data set was divided into a developmental
      subset for logistic regression modelling and a validation subset for model
      testing. A logistic risk model (EuroSCORE II) was then constructed and tested.
      RESULTS: Compared with the original 1995 EuroSCORE database (in brackets), the
      mean age was up at 64.7 (62.5) with 31% females (28%). More patients had New York
      Heart Association class IV, extracardiac arteriopathy, renal and pulmonary
      dysfunction. Overall mortality was 3.9% (4.6%). When applied to the current data,
      the old risk models overpredicted mortality (actual: 3.9%; additive predicted:
      5.8%; logistic predicted: 7.57%). EuroSCORE II was well calibrated on testing in
      the validation data subset of 5553 patients (actual mortality: 4.18%; predicted:
      3.95%). Very good discrimination was maintained with an area under the receiver
      operating characteristic curve of 0.8095. CONCLUSIONS: Cardiac surgical mortality
      has significantly reduced in the last 15 years despite older and sicker patients.
      EuroSCORE II is better calibrated than the original model yet preserves powerful
      discrimination. It is proposed for the future assessment of cardiac surgical
      risk.

PMID- 22378856
TI  - Editorial comment: myocardial protection with postconditioning in cardiac
      surgery: the importance of the model.

PMID- 22378857
TI  - Contemporary outcomes of urgent coronary artery bypass graft surgery following
      non-ST elevation myocardial infarction: urgent coronary artery bypass graft
      surgery consistently outperforms Global Registry of Acute Coronary Events
      predicted survival.
AB  - OBJECTIVES: The Global Registry of Acute Coronary Events (GRACE) registry
      reported that the in-hospital risk of death from non-ST elevation myocardial
      infarction (NSTEMI) is 5%, with an 11% mortality by 6 months. Prospective
      Registry of Acute Ischaemic Syndromes in the UK demonstrated that the overall
      risk of death from NSTEMI over 4 years is 25%. In GRACE, while 28% of patients
      received percutaneous intervention, only 10% received coronary artery bypass
      graft (CABG). Results of urgent CABG surgery following NSTEMI are difficult to
      interpret as these often include patients who have had STEMIs and urgent surgery.
      With increasing multidisciplinary assessment of patients with acute coronary
      syndromes (ACS), accurate data collection on the outcome of such patients could
      inform correct revascularization strategy. METHODS: Three hundred and forty-two
      consecutive patients who had undergone urgent CABG from April 2004 to April 2009
      at a single institution were identified. The GRACE predicted mortality was
      calculated from hospital records and patients categorized into three groups based
      upon their predicted risk. Late survival data were obtained from the UK Office of
      National Statistics. RESULTS: The GRACE score could be calculated in 270 patients
      with a confirmed diagnosis of NSTEMI. Of the 304 probable patients with NSTEMI,
      there were 5 in-hospital deaths (1.6%). Survival at 6 months was higher than
      GRACE predicted mortality in all groups. At 6 months the predicted versus
      observed mortality in the low-risk group was 4 versus 2% (P = 0.05), in the
      medium-risk group it was 12.5 versus 1.9% (P = 0.0001) and in the high-risk group
      it was 25 versus 20% (P = 0.45). CONCLUSIONS: In-hospital CABG performed after
      NSTEMI is associated with a low-mortality risk and survival significantly better
      than that predicted by the GRACE score.

PMID- 22378858
TI  - Plasma clusterin increased prior to small for gestational age (SGA) associated
      with preeclampsia and decreased prior to SGA in normotensive pregnancies.
AB  - In our search for early biomarkers for the pregnancy complicationssmall for
      gestational age (SGA) and preeclampsia (PE) we analysed plasma from 19-21 weeks
      gestation in women recruited into the SCOPE study, a prospective cohort of
      nulliparous women, by differential in gel electrophoresis (DIGE). DIGE revealed
      the differential expression of clusterin levels and its isoforms in top6-depleted
      plasma of women who delivered an SGA infant but remained normotensive (SGA-NT; N
      = 8) compared to healthy women with an uncomplicated pregnancy outcome (Controls,
      N = 8). Immunosorbent enzyme-linked assay (ELISA) showed that compared to plasma
      clusterin levels from healthy controls [71.1 (SD 12.4) ug/mL, n = 39], clusterin
      was decreased in SGA-NT [58.3 (SD 11.7), N = 20, P < 0.0001], increased in women
      with SGA and PE [81.5 (SD 14.8), N = 20, P < 0.01], but similar in PE alone [71.2
      (SD 9.4)g/ml, P = 1.0]. Screening for clusterin levels and/or its different
      isoformsmay be useful in mid-pregnancy to identify women who subsequently develop
      SGA but remain normotensive or who develop preeclampsia with SGA.

PMID- 22378859
TI  - Venous pulse transit time in normal pregnancy and preeclampsia.
AB  - Uncomplicated pregnancies (n = 16) were evaluated longitudinally and compared to
      early- (n = 12) and late-onset (n = 14) preeclampsia patients, assessed once at
      diagnosis. Pulse transit time (PTT), equivalent to pulse wave velocity, was
      measured as the time interval between corresponding characteristics of
      electrocardiography and Doppler waves, corrected for heart rate, at the level of
      renal interlobar veins, hepatic veins, and arcuate branches of uterine arteries.
      Impedance cardiography was used to measure PTT at the level of the thoracic
      aorta. In normal pregnancy, all PTT increased gradually (P <= .01). Pulse transit
      time was shorter in late-onset preeclampsia (P < .05) and also in early-onset
      preeclampsia, with exception for hepatic veins and thoracic aorta (P > .05). Our
      results indicate that PTT is an easy and highly accessible measure for vascular
      reactivity at both arterial and venous sites of the circulation. Our observations
      correlate well with known gestational cardiovascular adaptation mechanisms. This
      suggests that PTT could be used as a new parameter in the evaluation and
      prediction of preeclampsia.

PMID- 22378860
TI  - In vitro evidences of heparin's effects on embryo implantation and trophoblast
      development.
AB  - Heparin seems to be effective in ameliorating pregnancy outcome in thrombophilic
      women with previous recurrent pregnancy loss, preeclampsia, intrauterine growth
      restriction and sudden fetal death. A prophylactic effect of heparin treatment
      has also been proposed in terms of prevention of adverse pregnancy outcomes
      recurrence in women with history of recurrent miscarriage, severe preeclampsia,
      placental abruption, low neonatal birth weight and intrauterine fetal death not
      related to thrombophilia, although literature in this field is quite
      controversial. The molecular mechanisms by which heparin might exert its
      potential therapeutic effects in human reproduction are still not fully
      understood. In this article we review the current knowledge in this research
      field, focusing on in vitro evidences of heparin's mechanisms of action in the
      processes of embryo implantation and trophoblast invasion.

PMID- 22378861
TI  - G protein-coupled estrogen receptor (GPER) expression in normal and abnormal
      endometrium.
AB  - Rapid estrogen effects are mediated by membrane receptors, and evidence suggests
      a role for both a membrane-associated form of estrogen receptor alpha (ESR1;
      ERalpha) and G-protein coupled receptor 30 (GPER; GPR30). Considering estrogen's
      importance in endometrial physiology and endometriosis pathophysiology, we
      hypothesized that GPER could be involved in both cyclic changes in endometrial
      estrogen action and that aberrant expression might be seen in the eutopic
      endometrium of women with endometriosis. Using real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemical analysis of normal
      endometrium, endometrial samples demonstrated cycle-regulated expression of GPER,
      with maximal expression in the proliferative phase. Eutopic and ectopic
      endometrium from women with endometriosis overexpressed GPER as compared to
      eutopic endometrium of normal participants. Ishikawa cells, an adenocarcinoma
      cell line, expressed GPER, with increased expression upon treatment with estrogen
      or an ESR1 agonist, but not with a GPER-specific agonist. Decreased expression
      was seen in Ishikawa cells stably transfected with progesterone receptor A.
      Together, these data suggest that normal endometrial GPER expression is cyclic
      and regulated by nuclear estrogen and progesterone receptors, while expression is
      dysregulated in endometriosis.

PMID- 22378862
TI  - Apoptotic cell death correlates with ROS overproduction and early cytokine
      expression after hypoxia-ischemia in fetal lambs.
AB  - Despite advances in neonatology, the hypoxic-ischemic injury in the perinatal
      period remains the single most important cause of brain injury in the newborn,
      leading to death or lifelong sequelae. Using a sheep model of intrauterine
      asphyxia, we evaluated the correlation between reactive oxygen species (ROS)
      overproduction, cytokine expression, and apoptotic cell death. Fetal lambs were
      assigned to sham group, nonasphyctic animals; and hypoxia-ischemia (HI) group,
      lambs subjected to 60 minutes of HI) by partial cord occlusion and sacrificed 3
      hours later. Different brain regions were separated to quantify the number of
      apoptotic cells and the same territories were dissociated for flow cytometry
      studies. Our results suggest that the overproduction of ROS and the early
      increase in cytokine production after HI in fetal lambs correlate in a
      significant manner with the apoptotic index, as well as with each brain region
      evaluated.

PMID- 22378863
TI  - Detrimental effects of high-dose gonadotropin on outcome of IVF: making a case
      for gentle ovarian stimulation strategies.
AB  - OBJECTIVE: Limited data identify detrimental influences of aggressive use of
      gonadotropins (G) for controlled ovarian hyperstimulation (COH); the underlying
      mechanisms however remain unclear. We report on the relationship between G dose
      and in vitro fertilization (IVF) cycle parameters (ovarian response, endometrial
      thickness [EMT]) and cycle outcome (implantation rate [IR] and clinical pregnancy
      [CP] rate) in a cohort of women undergoing IVF. METHODS: Retrospective analysis
      of fresh embryo transfer (ET) cycles. Univariate and multivariable regression
      analyses assessed relationship between G dose and outcomes of interest. RESULTS:
      Higher G dose related positively with advancing age (P < .001) and inversely with
      EMT (P < .001). The overall CP rate was 30%. Significantly lower IR (.003) and CP
      rate (.002) were observed across increasing tertiles of G dose. Increasing G dose
      was identified as an independent negative predictor of EMT after adjusting for
      age, COH protocol and duration, infertility diagnosis, and ovarian response (P =
      .016). Adjusting for age, suppression protocol (gonadotropin-releasing hormone
      agonist vs antagonist), infertility diagnoses, EMT, quality, and cleavage of ET,
      lower G dose was an independent positive predictor of CP rate (odds ratio for CP
      rate was 1.57 for G dose in middle compared to the highest G dose quartile (95%
      confidence interval 1.09-2.24). Stratified analyses identified detrimental
      associations of higher G dose with CP rate to be relevant in women aged 35 years
      and younger. CONCLUSIONS: Our analyses suggest detrimental influences of higher G
      dose on the endometrium and confirm the previously reported adverse association
      between higher G dose and IVF outcome. Gentler COH regimens may be of particular
      benefit in women aged <=35 years.

PMID- 22378864
TI  - The association between microenvironmental reactive oxygen species and embryo
      development in assisted reproduction technology cycles.
AB  - This study was designed to determine the relevance between the levels of reactive
      oxygen species (ROS) in microenvironment (follicular fluid or culture media) and
      the embryo development in IVF/ICSI cycles. A total of 466 follicles from 174
      IVF/ICSI cycles were collected for this study. The ROS levels in monofollicular
      fluid and spent culture media were evaluated by chemiluminescence assay with
      luminol as a probe. The results demonstrated that it is in ICSI cycles that
      elevated ROS levels in follicular fluid were associated with day 3 poor embryo
      quality. The ROS levels in spent culture media were correlated with advanced
      degree of fragmentation. In addition, ROS levels in culture media, instead of in
      follicular fluid, were negatively correlated with implantation potential of
      embryos. The ROS levels in culture media may be viewed as an embryo metabolic
      marker and function as an adjuvant criterion for embryo selection.

PMID- 22378866
TI  - A unique mechanism of NMDA spike initiation supports a distinct role in synaptic
      input integration.

PMID- 22378865
TI  - Medical treatment of uterine leiomyoma.
AB  - Uterine leiomyomas (also called myomata or fibroids) are the most common
      gynecologic tumors in the United States. The prevalence of leiomyomas is at least
      3 to 4 times higher among African American women than in white women.
      Pathologically, uterine leiomyomas are benign tumors that arise in any part of
      the uterus under the influence of local growth factors and sex hormones, such as
      estrogen and progesterone. These common tumors cause significant morbidity for
      women and they are considered to be the most common indication for hysterectomy
      in the world; they are also associated with a substantial economic impact on
      health care systems that amounts to approximately $2.2 billion/year in the United
      States alone. Uterine myomas cause several reproductive problems such as heavy or
      abnormal uterine bleeding, pelvic pressure, infertility, and several obstetrical
      complications including miscarriage and preterm labor. Surgery has traditionally
      been the gold standard for the treatment of uterine leiomyomas and has typically
      consisted of either hysterectomy or myomectomy. In recent years, a few clinical
      trials have evaluated the efficacy of orally administered medications for the
      management of leiomyoma-related symptoms. In the present review, we will discuss
      these promising medical treatments in further detail.

PMID- 22378868
TI  - Foxg1 has an essential role in postnatal development of the dentate gyrus.
AB  - Foxg1, formerly BF-1, is expressed continuously in the postnatal and adult
      hippocampal dentate gyrus (DG). This transcription factor (TF) is thought to be
      involved in Rett syndrome, which is characterized by reduced hippocampus size,
      indicating its important role in hippocampal development. Due to the perinatal
      death of Foxg1(-/-) mice, the function of Foxg1 in postnatal DG neurogenesis
      remains to be explored. Here, we describe the generation of a Foxg1(fl/fl) mouse
      line. Foxg1 was conditionally ablated from the DG during prenatal and postnatal
      development by crossing this line with a Frizzled9-CreER(TM) line and inducing
      recombination with tamoxifen. In this study, we first show that disruption of
      Foxg1 results in the loss of the subgranular zone and a severely disrupted
      secondary radial glial scaffold, leading to the impaired migration of granule
      cells. Moreover, detailed analysis reveals that Foxg1 may be necessary for the
      maintenance of the DG progenitor pool and that the lack of Foxg1 promotes both
      gliogenesis and neurogenesis. We additionally show that Foxg1 may be required for
      the survival and maturation of postmitotic neurons and that Foxg1 may be involved
      in Reelin signaling in regulating postnatal DG development. Last, prenatal
      deletion of Foxg1 suggests that it is rarely involved in the migration of
      primordial granule cells. In summary, we report that Foxg1 is critical for DG
      formation, especially during early postnatal stage.

PMID- 22378867
TI  - 5-HT7R/G12 signaling regulates neuronal morphology and function in an age
      dependent manner.
AB  - The common neurotransmitter serotonin controls different aspects of early
      neuronal differentiation, although the underlying mechanisms are poorly
      understood. Here we report that activation of the serotonin 5-HT(7) receptor
      promotes synaptogenesis and enhances synaptic activity in hippocampal neurons at
      early postnatal stages. An analysis of Galpha(12)-deficient mice reveals a
      critical role of G(12)-protein for 5-HT(7) receptor-mediated effects in neurons.
      In organotypic preparations from the hippocampus of juvenile mice, stimulation of
      5-HT(7)R/G(12) signaling potentiates formation of dendritic spines, increases
      neuronal excitability, and modulates synaptic plasticity. In contrast, in older
      neuronal preparations, morphogenetic and synaptogenic effects of 5-HT(7)/G(12)
      signaling are abolished. Moreover, inhibition of 5-HT(7) receptor had no effect
      on synaptic plasticity in hippocampus of adult animals. Expression analysis
      reveals that the production of 5-HT(7) and Galpha(12)-proteins in the hippocampus
      undergoes strong regulation with a pronounced transient increase during early
      postnatal stages. Thus, regulated expression of 5-HT(7) receptor and Galpha(12)
      protein may represent a molecular mechanism by which serotonin specifically
      modulates formation of initial neuronal networks during early postnatal
      development.

PMID- 22378869
TI  - Supplementary eye field encodes reward prediction error.
AB  - The outcomes of many decisions are uncertain and therefore need to be evaluated.
      We studied this evaluation process by recording neuronal activity in the
      supplementary eye field (SEF) during an oculomotor gambling task. While the
      monkeys awaited the outcome, SEF neurons represented attributes of the chosen
      option, namely, its expected value and the uncertainty of this value signal.
      After the gamble result was revealed, a number of neurons reflected the actual
      reward outcome. Other neurons evaluated the outcome by encoding the difference
      between the reward expectation represented during the delay period and the actual
      reward amount (i.e., the reward prediction error). Thus, SEF encodes not only
      reward prediction error but also all the components necessary for its
      computation: the expected and the actual outcome. This suggests that SEF might
      actively evaluate value-based decisions in the oculomotor domain, independent of
      other brain regions.

PMID- 22378870
TI  - Mitral cells in the olfactory bulb are mainly excited through a multistep
      signaling path.
AB  - Within the olfactory system, information flow from the periphery onto output
      mitral cells (MCs) of the olfactory bulb (OB) has been thought to be mediated by
      direct synaptic inputs from olfactory sensory neurons (OSNs). Here, we performed
      patch-clamp measurements in rat and mouse OB slices to investigate mechanisms of
      OSN signaling onto MCs, including the assumption of a direct path, using
      electrical and optogenetic stimulation methods that selectively activated OSNs.
      We found that MCs are in fact not typically activated by direct OSN inputs and
      instead require a multistep, diffuse mechanism involving another glutamatergic
      cell type, the tufted cells. The preference for a multistep mechanism reflects
      the fact that signals arising from direct OSN inputs are drastically shunted by
      connexin 36-mediated gap junctions on MCs, but not tufted cells. An OB circuit
      with tufted cells intermediate between OSNs and MCs suggests that considerable
      processing of olfactory information occurs before its reaching MCs.

PMID- 22378871
TI  - Neuronal birth order identifies a dimorphic sensorineural map.
AB  - Spatially distributed sensory information is topographically mapped in the brain
      by point-to-point correspondence of connections between peripheral receptors and
      central target neurons. In fishes, for example, the axonal projections from the
      mechanosensory lateral line organize a somatotopic neural map. The lateral line
      provides hydrodynamic information for intricate behaviors such as navigation and
      prey detection. It also mediates fast startle reactions triggered by the Mauthner
      cell. However, it is not known how the lateralis neural map is built to subserve
      these contrasting behaviors. Here we reveal that birth order diversifies
      lateralis afferent neurons in the zebrafish. We demonstrate that early- and late
      born lateralis afferents diverge along the main axes of the hindbrain to synapse
      with hundreds of second-order targets. However, early-born afferents projecting
      from primary neuromasts also assemble a separate map by converging on the lateral
      dendrite of the Mauthner cell, whereas projections from secondary neuromasts
      never make physical contact with the Mauthner cell. We also show that neuronal
      diversity and map topology occur normally in animals permanently deprived of
      mechanosensory activity. We conclude that neuronal birth order correlates with
      the assembly of neural submaps, whose combination is likely to govern appropriate
      behavioral reactions to the sensory context.

PMID- 22378872
TI  - The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors
      associated with psychiatric disorders.
AB  - Neuregulin 1 (NRG-1) and its receptor ErbB4 have emerged as biologically
      plausible schizophrenia risk factors, modulators of GABAergic and dopaminergic
      neurotransmission, and as potent regulators of glutamatergic synaptic plasticity.
      NRG-1 acutely depotentiates LTP in hippocampal slices, and blocking ErbB kinase
      activity inhibits LTP reversal by theta-pulse stimuli (TPS), an activity
      dependent reversal paradigm. NRG-1/ErbB4 signaling in parvalbumin (PV)
      interneurons has been implicated in inhibitory transmission onto pyramidal
      neurons. However, the role of ErbB4, in particular in PV interneurons, for LTP
      reversal has not been investigated. Here we show that ErbB4-null (ErbB4(-/-)) and
      PV interneuron-restricted mutant (PV-Cre;ErbB4) mice, as well as NRG-1
      hypomorphic mice, exhibit increased hippocampal LTP. Moreover, both ErbB4(-/-)
      and PV-Cre;ErbB4 mice lack TPS-mediated LTP reversal. A comparative behavioral
      analysis of full and conditional ErbB4 mutant mice revealed that both exhibit
      hyperactivity in a novel environment and deficits in prepulse inhibition of the
      startle response. Strikingly, however, only ErbB4(-/-) mice exhibit reduced
      anxiety-like behaviors in the elevated plus maze task and deficits in cued and
      contextual fear conditioning. These results suggest that aberrant NRG-1/ErbB4
      signaling in PV interneurons accounts for some but not all behavioral
      abnormalities observed in ErbB4(-/-) mice. Consistent with the observation that
      PV-Cre;ErbB4 mice exhibit normal fear conditioning, we find that ErbB4 is broadly
      expressed in the amygdala, largely by cells negative for PV. These findings are
      important to better understand ErbB4's role in complex behaviors and warrant
      further analysis of ErbB4 mutant mice lacking the receptor in distinct neuron
      types.

PMID- 22378873
TI  - Neurons with stereotyped and rapid responses provide a reference frame for
      relative temporal coding in primate auditory cortex.
AB  - The precise timing of spikes of cortical neurons relative to stimulus onset
      carries substantial sensory information. To access this information the sensory
      systems would need to maintain an internal temporal reference that reflects the
      precise stimulus timing. Whether and how sensory systems implement such reference
      frames to decode time-dependent responses, however, remains debated. Studying the
      encoding of naturalistic sounds in primate (Macaca mulatta) auditory cortex we
      here investigate potential intrinsic references for decoding temporally precise
      information. Within the population of recorded neurons, we found one subset
      responding with stereotyped fast latencies that varied little across trials or
      stimuli, while the remaining neurons had stimulus-modulated responses with longer
      and variable latencies. Computational analysis demonstrated that the neurons with
      stereotyped short latencies constitute an effective temporal reference for
      relative coding. Using the response onset of a simultaneously recorded
      stereotyped neuron allowed decoding most of the stimulus information carried by
      onset latencies and the full spike train of stimulus-modulated neurons.
      Computational modeling showed that few tens of such stereotyped reference neurons
      suffice to recover nearly all information that would be available when decoding
      the same responses relative to the actual stimulus onset. These findings reveal
      an explicit neural signature of an intrinsic reference for decoding temporal
      response patterns in the auditory cortex of alert animals. Furthermore, they
      highlight a role for apparently unselective neurons as an early saliency signal
      that provides a temporal reference for extracting stimulus information from other
      neurons.

PMID- 22378874
TI  - A candidate mechanism underlying the variance of interictal spike propagation.
AB  - Synchronous activation of neural networks is an important physiological
      mechanism, and dysregulation of synchrony forms the basis of epilepsy. We
      analyzed the propagation of synchronous activity through chronically epileptic
      neural networks. Electrocorticographic recordings from epileptic patients
      demonstrate remarkable variance in the pathways of propagation between sequential
      interictal spikes (IISs). Calcium imaging in chronically epileptic slice cultures
      demonstrates that pathway variance depends on the presence of GABAergic
      inhibition and that spike propagation becomes stereotyped following GABA receptor
      blockade. Computer modeling suggests that GABAergic quenching of local network
      activations leaves behind regions of refractory neurons, whose late recruitment
      forms the anatomical basis of variability during subsequent network activation.
      Targeted path scanning of slice cultures confirmed local activations, while ex
      vivo recordings of human epileptic tissue confirmed the dependence of interspike
      variance on GABA-mediated inhibition. These data support the hypothesis that the
      paths by which synchronous activity spreads through an epileptic network change
      with each activation, based on the recent history of localized activity that has
      been successfully inhibited.

PMID- 22378875
TI  - Disruption of prefrontal cortex large scale neuronal activity by different
      classes of psychotomimetic drugs.
AB  - In the absence of overt cellular pathology but profound perceptual
      disorganization and cognitive deficits, schizophrenia is increasingly considered
      a disorder of neural coordination. Thus, different causal factors can similarly
      interrupt the dynamic function of neuronal ensembles and networks, in particular
      in the prefrontal cortex (PFC), leading to behavioral disorganization. The
      importance of establishing preclinical biomarkers for this aberrant function has
      prompted investigations into the nature of psychotomimetic drug effects on PFC
      neuronal activity. The drugs used in this context include serotonergic
      hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of
      thinking is that these drugs create psychotomimetic states by similarly
      disinhibiting the activity of PFC pyramidal neurons. In the present study we did
      not find evidence in support of this mechanism in PFC subregions of freely moving
      rats. Whereas the NMDA receptor antagonist MK801 increased PFC population
      activity, the serotonergic hallucinogen DOI dose-dependently decreased population
      activity. Amphetamine did not strongly affect this measure. Despite different
      effects on the direction of change in activity, all three drugs caused similar
      net disruptions of population activity and modulated gamma oscillations. We also
      observed reduced correlations between spike-rate and local field potential power
      selectively in the gamma band suggesting that these drugs disconnect spike
      discharge from PFC gamma oscillators. Gamma band oscillations support cognitive
      functions affected in schizophrenia. These findings provide insight into
      mechanisms that may lead to cortical processing deficits in schizophrenia and
      provide a novel electrophysiological approach for phenotypic characterization of
      animal models of this disease.

PMID- 22378876
TI  - Thyrotropin-releasing hormone (TRH) inhibits melanin-concentrating hormone
      neurons: implications for TRH-mediated anorexic and arousal actions.
AB  - Thyrotropin-releasing hormone (TRH) increases activity and decreases food intake,
      body weight, and sleep, in part through hypothalamic actions. The mechanism of
      this action is unknown. Melanin-concentrating hormone (MCH) and hypocretin/orexin
      neurons in the lateral hypothalamus (LH) together with neuropeptide Y (NPY) and
      proopiomelanocortin (POMC) neurons in the arcuate nucleus play central roles in
      energy homeostasis. Here, we provide electrophysiological evidence from GFP
      reporter transgenic mouse brain slices that shows TRH modulates the activity of
      MCH neurons. Using whole-cell current-clamp recording, we unexpectedly found that
      TRH and its agonist, montrelin, dose-dependently inhibited MCH neurons.
      Consistent with previous reports, TRH excited hypocretin/orexin neurons. No
      effect was observed on arcuate nucleus POMC or NPY neurons. The TRH inhibition of
      MCH neurons was eliminated by bicuculline and tetrodotoxin, suggesting that the
      effect was mediated indirectly through synaptic mechanisms. TRH increased
      spontaneous IPSC frequency without affecting amplitude and had no effect on
      miniature IPSCs or EPSCs. Immunocytochemistry revealed little interaction between
      TRH axons and MCH neurons, but showed TRH axons terminating on or near GABA
      neurons. TRH inhibition of MCH neurons was attenuated by Na(+)-Ca(2+) exchanger
      (NCX) inhibitors, TRPC channel blockers and the phospholipase C inhibitor U
      73122. TRH excited LH GABA neurons, and this was also reduced by NCX inhibitors.
      Finally, TRH attenuated the excitation of MCH neurons by hypocretin. Together,
      our data suggest that TRH inhibits MCH neurons by increasing synaptic inhibition
      from local GABA neurons. Inhibition of MCH neurons may contribute to the TRH
      mediated reduction in food intake and sleep.

PMID- 22378877
TI  - Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated
      claudin-5 redistribution contribute to blood-brain barrier damage in early
      ischemic stroke stage.
AB  - Blood-brain barrier (BBB) disruption occurs early enough to be within the
      thrombolytic time window, and this early ischemic BBB damage is closely
      associated with hemorrhagic transformation and thus emerging as a promising
      target for reducing the hemorrhagic complications of thrombolytic stroke therapy.
      However, the mechanisms underlying early ischemic BBB damage remain poorly
      understood. Here, we investigated the early molecular events of ischemic BBB
      damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle
      cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2
      h significantly increased its permeability to FITC-labeled dextran and promoted
      the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation
      of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of
      tight junction protein occludin and dissociation of claudin-5 from the
      cytoskeleton, which contributed to OGD-induced endothelial barrier disruption.
      Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]
      thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2
      was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was
      responsible for claudin-5 redistribution. The interaction between Cav-1 and
      claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these
      in vitro findings, we observed fluorescence tracer extravasation, increased
      gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic
      subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5
      redistribution were detected in ischemic cerebromicrovessels. These data indicate
      that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated
      occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB
      disruption at early stroke stages relevant to acute thrombolysis.

PMID- 22378878
TI  - P2X4 receptors influence inflammasome activation after spinal cord injury.
AB  - P2X(4) and P2X(7) are the predominant purinergic P2X receptor subtypes expressed
      on immune and neural cells. These receptor subtypes traffic between intracellular
      compartments and the plasma membrane and form protein interactions with each
      other to regulate ATP-dependent signaling. Our recent studies have shown that
      P2X(7) receptors in neurons and astrocytes activate NLRP1 inflammasomes, but
      whether P2X(4) receptors regulate inflammasome signaling is essentially unknown.
      Here, we demonstrate that P2X(4) receptors are expressed in neurons of the spinal
      cord. We provide direct evidence that spinal cord injury (SCI) induces an innate
      inflammatory response that leads to increased caspase-l cleavage and production
      of IL-1beta but not IL-18. Consistent with these findings, P2X(4) knock-out mice
      showed impaired inflammasome signaling in the cord, resulting in decreased levels
      of IL-1beta and reduced infiltration of neutrophils and monocyte-derived M1
      macrophages, resulting in significant tissue sparing and improvement in
      functional outcomes. These results indicate that P2X(4) receptors influence
      inflammasome signaling involving caspase-1 activation and IL-1beta processing in
      neurons after SCI. P2X(4) might thus represent a potential therapeutic target to
      limit inflammatory responses associated with SCI and neurodegenerative disorders.

PMID- 22378879
TI  - SoxC transcription factors are required for neuronal differentiation in adult
      hippocampal neurogenesis.
AB  - Neural stem cells (NSCs) generate new hippocampal dentate granule neurons
      throughout adulthood. The genetic programs controlling neuronal differentiation
      of adult NSCs are only poorly understood. Here we show that, in the adult mouse
      hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is
      initiated around the time of neuronal commitment of adult NSCs and is maintained
      in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro
      neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro
      and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC
      transcription factors target the promoters of genes that are induced on neuronal
      differentiation of adult NSCs. Finally, we show that reprogramming of astroglia
      into neurons is dependent on the presence of SoxC factors. These data identify
      SoxC proteins as essential contributors to the genetic network controlling
      neuronal differentiation in adult neurogenesis and neuronal reprogramming of
      somatic cells.

PMID- 22378880
TI  - Astrocyte-originated ATP protects Abeta(1-42)-induced impairment of synaptic
      plasticity.
AB  - Activated microglia and reactive astrocytes are commonly found in and around the
      senile plaque, which is the central pathological hallmark of Alzheimer's disease.
      Astrocytes respond to neuronal activity through the release of gliotransmitters
      such as glutamate, D-serine, and ATP. However, it is largely unknown whether and
      how gliotransmitters affect neuronal functions. In this study, we explored the
      effect of a gliotransmitter, ATP, on neurons damaged by beta-amyloid peptide
      (Abeta). We found that Abeta(1-42) (Abeta42) increased the release of ATP in
      cultures of primary astrocytes and U373 astrocyte cell line. We also found that
      exogenous ATP protected Abeta42-mediated reduction in synaptic molecules, such as
      NMDA receptor 2A and PSD-95, through P2 purinergic receptors and prevented
      Abeta42-induced spine reduction in cultured primary hippocampal neurons.
      Moreover, ATP prevented Abeta42-induced impairment of long-term potentiation in
      acute hippocampal slices. Our findings suggest that Abeta-induced release of
      gliotransmitter ATP plays a protective role against Abeta42-mediated disruption
      of synaptic plasticity.

PMID- 22378881
TI  - Robustness of traveling waves in ongoing activity of visual cortex.
AB  - Numerous studies have revealed traveling waves of activity in sensory cortex,
      both following sensory stimulation and during ongoing activity. We contributed to
      this body of work by measuring the spike-triggered average of the local field
      potential (stLFP) at multiple concurrent locations (Nauhaus et al., 2009) in the
      visual cortex of anesthetized cats and macaques. We found the stLFP to be
      progressively delayed at increasing distances from the site of the triggering
      spikes, and interpreted this as a traveling wave of depolarization originating
      from that site. Our results were criticized, however, on two grounds. First, a
      study using the same recording techniques in the visual cortex of awake macaques
      reported an apparent lack of traveling waves, and proposed that traveling waves
      could arise artifactually from excessive filtering of the field potentials (Ray
      and Maunsell, 2011). Second, the interpretability of the stLFP was questioned
      (Kenneth Miller, personal communication), as the stLFP must reflect not only
      interactions between spike trains and field potentials, but also correlations
      within and across the spike trains. Here, we show that our data and
      interpretation are not imperiled by these criticisms. We reanalyzed our field
      potentials to remove any possible artifact due to filtering and to discount the
      effects of correlations within and across the triggering spike trains. In both
      cases, we found that the traveling waves were still present. In fact, closer
      inspection of Ray and Maunsell's (2011) data from awake cortex shows that they do
      agree with ours, as they contain clear evidence for traveling waves.

PMID- 22378882
TI  - Modulation of olfactory perception by visual cortex stimulation.
AB  - When attempting to identify an object based on smell alone, people often
      visualize the perceived source of the odorant. This close association between
      olfactory and visual functions is supported by neuroimaging studies demonstrating
      activation of visual cortex during performance of purely olfactory tasks. Such
      activation might simply reflect the correlation between olfactory percepts and
      the corresponding visual images, or it might reflect a causal contribution of
      visual processing to olfactory perception. Here we provide evidence in support of
      the latter possibility. Using repetitive transcranial magnetic stimulation, we
      show that stimulating human visual cortex improves performance on a task
      requiring discrimination among different odor qualities. No significant
      improvement is found for tasks involving discrimination between intensities of
      the same odor, from stimulation of auditory cortex, or from "sham" stimulation.
      These results are thus consistent with a specific visual cortical influence on
      high-level olfactory perception. They also demonstrate that unimodal perceptual
      tasks are influenced by processing within cortical areas of other, seemingly
      unrelated, sensory systems.

PMID- 22378883
TI  - Long-lasting plasticity of hippocampal adult-born neurons.
AB  - Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key
      structure in learning and memory. It is believed that adult-born neurons exert
      their unique role in information processing due to their high plasticity during
      immature stage that renders them malleable in response to environmental demands.
      Here, we demonstrate that, in rats, there is no critical time window for
      experience-induced dendritic plasticity of adult-born neurons as spatial learning
      in the water maze sculpts the dendritic arbor of adult-born neurons even when
      they are several months of age. By ablating neurogenesis within a specific period
      of time, we found that learning was disrupted when the delay between ablation and
      learning was extended to several months. Together, these results show that mature
      adult-born neurons are still plastic when they are functionally integrated into
      dentate network. Our results suggest a new perspective with regard to the role of
      neo-neurons by highlighting that even mature ones can provide an additional
      source of plasticity to the brain to process memory information.

PMID- 22378884
TI  - A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs
      learning and memory and synaptic transmission.
AB  - Rett syndrome and MECP2 duplication syndrome are neurodevelopmental disorders
      that arise from loss-of-function and gain-of-function alterations in methyl-CpG
      binding protein 2 (MeCP2) expression, respectively. Although there have been
      studies examining MeCP2 loss of function in animal models, there is limited
      information on MeCP2 overexpression in animal models. Here, we characterize a
      mouse line with MeCP2 overexpression restricted to neurons (Tau-Mecp2). This
      MeCP2 overexpression line shows motor coordination deficits, heightened anxiety,
      and impairments in learning and memory that are accompanied by deficits in long
      term potentiation and short-term synaptic plasticity. Whole-cell voltage-clamp
      recordings of cultured hippocampal neurons from Tau-Mecp2 mice reveal augmented
      frequency of miniature EPSCs with no change in miniature IPSCs, indicating that
      overexpression of MeCP2 selectively impacts excitatory synapse function.
      Moreover, we show that alterations in transcriptional repression mechanisms
      underlie the synaptic phenotypes in hippocampal neurons from the Tau-Mecp2 mice.
      These results demonstrate that the Tau-Mecp2 mouse line recapitulates many key
      phenotypes of MECP2 duplication syndrome and support the use of these mice to
      further study this devastating disorder.

PMID- 22378885
TI  - Measuring the firing rate of high-resistance neurons with cell-attached
      recording.
AB  - Cell-attached recording is extensively used to study the firing rate of mammalian
      neurons, but potential limitations of the method have not been investigated in
      detail. Here we perform cell-attached recording of molecular layer interneurons
      in cerebellar slices from rats and mice, and we study how experimental conditions
      influence the measured firing rate. We find that this rate depends on time in
      cell-attached mode, on pipette potential, and on pipette ionic composition. In
      the first minute after sealing, action currents are variable in shape and size,
      presumably reflecting membrane instability. The firing rate remains approximately
      constant during the first 4 min after sealing and gradually increases afterward.
      Making the pipette potential more positive leads to an increase in the firing
      rate, with a steeper dependence on voltage if the pipette solution contains K(+)
      as the main cation than if it contains Na(+). Ca(2+) imaging experiments show
      that establishing a cell-attached recording can result in an increased somatic
      Ca(2+) concentration, reflecting an increased firing rate linked to an increase
      in the pipette-cell conductance. Pipette effects on cell firing are traced to a
      combination of passive electrical coupling, opening of voltage- and Ca(2+)
      sensitive K(+) channels (BK channels) after action potentials, and random
      activation of voltage-insensitive, presumably mechanosensitive, cationic
      channels. We conclude that, unless experimental conditions are optimized, cell
      attached recordings in small neurons may report erroneous firing rates.

PMID- 22378886
TI  - A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo.
AB  - Fluorescent calcium indicator proteins, such as GCaMP3, allow imaging of activity
      in genetically defined neuronal populations. GCaMP3 can be expressed using
      various gene delivery methods, such as viral infection or electroporation.
      However, these methods are invasive and provide inhomogeneous and nonstationary
      expression. Here, we developed a genetic reporter mouse, Ai38, which expresses
      GCaMP3 in a Cre-dependent manner from the ROSA26 locus, driven by a strong CAG
      promoter. Crossing Ai38 with appropriate Cre mice produced robust GCaMP3
      expression in defined cell populations in the retina, cortex, and cerebellum. In
      the primary visual cortex, visually evoked GCaMP3 signals showed normal
      orientation and direction selectivity. GCaMP3 signals were rapid, compared with
      virally expressed GCaMP3 and synthetic calcium indicators. In the retina, Ai38
      allowed imaging spontaneous calcium waves in starburst amacrine cells during
      development, and light-evoked responses in ganglion cells in adult tissue. Our
      results show that the Ai38 reporter mouse provides a flexible method for targeted
      expression of GCaMP3.

PMID- 22378887
TI  - CNG-modulin: a novel Ca-dependent modulator of ligand sensitivity in cone
      photoreceptor cGMP-gated ion channels.
AB  - The transduction current in several different types of sensory neurons arises
      from the activity of cyclic nucleotide-gated (CNG) ion channels. The channels in
      these sensory neurons vary in structure and function, yet each one demonstrates
      calcium-dependent modulation of ligand sensitivity mediated by the interaction of
      the channel with a soluble modulator protein. In cone photoreceptors, the
      molecular identity of the modulator protein was previously unknown. We report the
      discovery and characterization of CNG-modulin, a novel 301 aa protein that
      interacts with the N terminus of the beta subunit of the cGMP-gated channel and
      modulates the cGMP sensitivity of the channels in cone photoreceptors of striped
      bass (Morone saxatilis). Immunohistochemistry and single-cell PCR demonstrate
      that CNG-modulin is expressed in cone but not rod photoreceptors. Adding purified
      recombinant CNG-modulin to cone membrane patches containing the native CNG
      channels shifts the midpoint of cGMP dependence from ~91 MUM in the absence of
      Ca(2+) to ~332 MUM in the presence of 20 MUM Ca(2+). At a fixed cGMP
      concentration, the midpoint of the Ca(2+) dependence is ~857 nM Ca(2+). These
      restored physiological features are statistically indistinguishable from the
      effects of the endogenous modulator. CNG-modulin binds Ca(2+) with a
      concentration dependence that matches the calcium dependence of channel
      modulation. We conclude that CNG-modulin is the authentic Ca(2+)-dependent
      modulator of cone CNG channel ligand sensitivity. CNG-modulin is expressed in
      other tissues, such as brain, olfactory epithelium, and the inner ear, and may
      modulate the function of ion channels in those tissues as well.

PMID- 22378888
TI  - CXCL16 orchestrates adenosine A3 receptor and MCP-1/CCL2 activity to protect
      neurons from excitotoxic cell death in the CNS.
AB  - A role for chemokines as molecules mediating neuron-glia cross talk has emerged
      in recent years, both in physiological and pathological conditions. We
      demonstrate here for the first time that the chemokine CXCL16 and its unique
      receptor CXCR6 are functionally expressed in the CNS, and induce neuroprotection
      against excitotoxic damage due to excessive glutamate (Glu) exposure and oxygen
      glucose deprivation (OGD). In mice and rats we found that, to exert
      neuroprotection, CXCL16 requires the presence of extracellular adenosine (ADO),
      and that pharmacological or genetic inactivation of the ADO A(3) receptor, A(3)R,
      prevents CXCL16 effect. In experiments with astrocytes cocultured with
      cxcr6(gfp/gfp) hippocampal cells, we demonstrate that CXCL16 acts directly on
      astrocytes to release soluble factors that are essential to mediate
      neuroprotection. In particular, we report that (1) upon stimulation with CXCL16
      astrocytes release monocyte chemoattractant protein-1/CCL2 and (2) the
      neuroprotective effect of CXCL16 is reduced in the presence of neutralizing CCL2
      antibody. In conclusion, we found that chemokine CXCL16 is able to mediate cross
      talk between astrocytes and neighboring neurons and, in pathological conditions
      such as excessive Glu or OGD exposure, is able to counteract neuronal cell death
      through an ADO-dependent chemokine-induced chemokine-release mechanism.

PMID- 22378889
TI  - Role of HCN channels in neuronal hyperexcitability after subarachnoid hemorrhage
      in rats.
AB  - Disruption of ionic homeostasis and neuronal hyperexcitability contribute to
      early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization
      activated/cyclic nucleotide (HCN)-gated channels play critical role in the
      regulation of neuronal excitability in hippocampus CA1 region and neocortex, in
      which the abnormal neuronal activities are more readily provoked. This study was
      to investigate the interactions between HCN channels and hyperneuronal activity
      after experimental SAH. The present results from whole-cell recordings in rat
      brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing
      artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in
      CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser
      of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in
      CA1 pyramidal neurons, while L-nitroarginine (L-NNA), an inhibitor of nitric
      oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on
      HCN currents was reversed by application of NO/Sp, which also reduced neuronal
      hyperexcitability; conversely, L-NNA enhanced inhibitory action of Hb on HCN
      currents. Additionally, Hb perfusion scavenged the production of nitric oxide and
      decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model,
      the expression of HCN1, both at mRNA and protein level, decreased in hippocampus
      CA1 region at 24 h and more pronounced at 72 h after SAH. These observations
      demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN
      currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb
      may be a novel pathway for inducing the hyperneuronal excitability after SAH.

PMID- 22378890
TI  - Inhibition of the NFAT pathway alleviates amyloid beta neurotoxicity in a mouse
      model of Alzheimer's disease.
AB  - Amyloid beta (Abeta) peptides, the main pathological species associated with
      Alzheimer's disease (AD), disturb intracellular calcium homeostasis, which in
      turn activates the calcium-dependent phosphatase calcineurin (CaN). CaN
      activation induced by Abeta leads to pathological morphological changes in
      neurons, and overexpression of constitutively active calcineurin is sufficient to
      generate a similar phenotype, even without Abeta. Here, we tested the hypothesis
      that calcineurin mediates neurodegenerative effects via activation of the nuclear
      transcription factor of activated T-cells (NFAT). We found that both spine loss
      and dendritic branching simplification induced by Abeta exposure were mimicked by
      constitutively active NFAT, and abolished when NFAT activation was blocked using
      the genetically encoded inhibitor VIVIT. When VIVIT was specifically addressed to
      the nucleus, identical beneficial effects were observed, thus enforcing the role
      of NFAT transcriptional activity in Abeta-related neurotoxicity. In vivo, when
      VIVIT or its nuclear counterpart were overexpressed in a transgenic model of
      Alzheimer's disease via a gene therapy approach, the spine loss and neuritic
      abnormalities observed in the vicinity of amyloid plaques were blocked. Overall,
      these results suggest that NFAT/calcineurin transcriptional cascades contribute
      to Abeta synaptotoxicity, and may provide a new specific set of pathways for
      neuroprotective strategies.

PMID- 22378891
TI  - Activity related to perceptual judgment and action in primary auditory cortex.
AB  - Recent evidence is reshaping the view of primary auditory cortex (A1) from a
      unisensory area to one more involved in dynamically integrating multisensory- and
      task-related information. We found A1 single- (SU) and multiple-unit (MU)
      activity correlated with macaques' choices in an amplitude modulation (AM)
      discrimination task. Animals were trained to discriminate AM noise from
      unmodulated noise by releasing a lever for AM noise and holding down the lever
      for unmodulated noise. Activity for identical stimuli was compared between trials
      where the animals reported AM and trials where they did not. We found 47.4% of
      MUs and 22.8% of SUs significantly increased firing shortly before the animal's
      behavioral response to report AM when compared to the equivalent time period on
      trials where AM was not reported. Activity was also linked to lever release in a
      different task context, suggesting A1 modulation by somatosensory, or efference
      copy, input. When spikes were counted only during the stimulus, 19.6% of MUs and
      13.8% of SUs increased firing rate when animals reported AM compared to when they
      did not, suggesting an attentional effect, or that A1 activity can be used by
      higher decision areas, or that such areas provide feedback to A1. Activity
      associated with AM reporting was correlated with a unit's AM sensitivity,
      suggesting AM sensitive neurons' involvement in task performance. A1 neurons'
      phase locking to AM correlated more weakly (compared to firing rate) with the
      animals' report of AM, suggesting a preferential role for rate-codes in A1 for
      this AM discrimination task.

PMID- 22378892
TI  - Functional expansion of sensorimotor representation and structural reorganization
      of callosal connections in lower limb amputees.
AB  - Previous studies have indicated that amputation or deafferentation of a limb
      induces functional changes in sensory (S1) and motor (M1) cortices, related to
      phantom limb pain. However, the extent of cortical reorganization after lower
      limb amputation in patients with nonpainful phantom phenomena remains uncertain.
      In this study, we combined functional magnetic resonance (fMRI) and diffusion
      tensor imaging (DTI) to investigate the existence and extent of cortical and
      callosal plasticity in these subjects. Nine "painless" patients with lower limb
      amputation and nine control subjects (sex- and age-matched) underwent a 3-T MRI
      protocol, including fMRI with somatosensory stimulation. In amputees, we observed
      an expansion of activation maps of the stump in S1 and M1 of the deafferented
      hemisphere, spreading to neighboring regions that represent the trunk and upper
      limbs. We also observed that tactile stimulation of the intact foot in amputees
      induced a greater activation of ipsilateral S1, when compared with controls.
      These results demonstrate a functional remapping of S1 in lower limb amputees.
      However, in contrast to previous studies, these neuroplastic changes do not
      appear to be dependent on phantom pain but do also occur in those who reported
      only the presence of phantom sensation without pain. In addition, our findings
      indicate that amputation of a limb also induces changes in the cortical
      representation of the intact limb. Finally, DTI analysis showed structural
      changes in the corpus callosum of amputees, compatible with the hypothesis that
      phantom sensations may depend on inhibitory release in the sensorimotor cortex.

PMID- 22378893
TI  - Vision for action in the macaque medial posterior parietal cortex.
AB  - Area V6A encodes hand configurations for grasping objects (Fattori et al., 2010).
      The aim of the present study was to investigate whether V6A cells also encode
      three-dimensional objects, and the relationship between object encoding and grip
      encoding. Single neurons were recorded in V6A of two monkeys trained to perform
      two tasks. In the first task, the monkeys were required to passively view an
      object without performing any action on it. In the second task, the monkeys
      viewed an object at the beginning of each trial and then they needed to grasp
      that object in darkness. Five different objects were used. Both tasks revealed
      that object presentation activates ~60% of V6A neurons, with about half of them
      displaying object selectivity. In the Reach-to-Grasp task, the majority of V6A
      cells discharged during both object presentation and grip execution, displaying
      selectivity for either the object or the grip, or in some cases for both object
      and grip. Although the incidence of neurons encoding grips was twofold that of
      neurons encoding objects, object selectivity in single cells was as strong as
      grip selectivity, indicating that V6A cells were able to discriminate both the
      different objects and the different grips required to grasp them. Hierarchical
      cluster analysis revealed that clustering of the object-selective responses
      depended on the task requirements (view only or view to grasp) and followed a
      visual or a visuomotor rule, respectively. Object encoding in V6A reflects
      representations for action, useful for motor control in reach-to-grasp.

PMID- 22378895
TI  - Notch signaling controls generation of motor neurons in the lesioned spinal cord
      of adult zebrafish.
AB  - In mammals, increased Notch signaling is held partly responsible for a lack of
      neurogenesis after a spinal injury. However, this is difficult to test in an
      essentially nonregenerating system. We show that in adult zebrafish, which
      exhibit lesion-induced neurogenesis, e.g., of motor neurons, the Notch pathway is
      also reactivated. Although apparently compatible with neuronal regeneration in
      zebrafish, forced activity of the pathway significantly decreased progenitor
      proliferation and motor neuron generation. Conversely, pharmacological inhibition
      of the pathway increased proliferation and motor neuron numbers. This
      demonstrates that Notch is a negative signal for regenerative neurogenesis, and,
      importantly, that spinal motor neuron regeneration can be augmented in an adult
      vertebrate by inhibiting Notch signaling.

PMID- 22378894
TI  - The oxygen free radicals originating from mitochondrial complex I contribute to
      oxidative brain injury following hypoxia-ischemia in neonatal mice.
AB  - Oxidative stress and Ca(2+) toxicity are mechanisms of hypoxic-ischemic (HI)
      brain injury. This work investigates if partial inhibition of mitochondrial
      respiratory chain protects HI brain by limiting a generation of oxidative
      radicals during reperfusion. HI insult was produced in p10 mice treated with
      complex I (C-I) inhibitor, pyridaben, or vehicle. Administration of P
      significantly decreased the extent of HI injury. Mitochondria isolated from the
      ischemic hemisphere in pyridaben-treated animals showed reduced H(2)O(2)
      emission, less oxidative damage to the mitochondrial matrix, and increased
      tolerance to the Ca(2+)-triggered opening of the permeability transition pore. A
      protective effect of pyridaben administration was also observed when the
      reperfusion-driven oxidative stress was augmented by the exposure to 100% O(2)
      which exacerbated brain injury only in vehicle-treated mice. In vitro, intact
      brain mitochondria dramatically increased H(2)O(2) emission in response to
      hyperoxia, resulting in substantial loss of Ca(2+) buffering capacity. However,
      in the presence of the C-I inhibitor, rotenone, or the antioxidant, catalase,
      these effects of hyperoxia were abolished. Our data suggest that the reperfusion
      driven recovery of C-I-dependent mitochondrial respiration contributes not only
      to the cellular survival, but also causes oxidative damage to the mitochondria,
      potentiating a loss of Ca(2+) buffering capacity. This highlights a novel
      neuroprotective strategy against HI brain injury where the major therapeutic
      principle is a pharmacological attenuation, rather than an enhancement of
      mitochondrial oxidative metabolism during early reperfusion.

PMID- 22378898
TI  - Adaptation of granule cell to Purkinje cell synapses to high-frequency
      transmission.
AB  - The mossy fiber (MF)-granule cell (GC) pathway conveys multiple modalities of
      information to the cerebellar cortex, converging on Purkinje cells (PC), the sole
      output of the cerebellar cortex. Recent in vivo experiments have shown that
      activity in GCs varies from tonic firing at a few hertz to phasic bursts >500 Hz.
      However, the responses of parallel fiber (PF)-PC synapses to this wide range of
      input frequencies are unknown, and there is controversy regarding several
      frequency-related parameters of transmission at this synapse. We performed
      recordings of unitary synapses and combined variance-mean analysis with a
      carefully adapted extracellular stimulation method in young and adult rats. We
      show that, although the probability of release at individual sites is low at
      physiological calcium concentration, PF-PC synapses release one or more vesicles
      with a probability of 0.44 at 1.5 mm [Ca(2+)](e). Paired-pulse facilitation was
      observed over a wide range of frequencies; it renders burst inputs particularly
      effective and reproducible. These properties are primarily independent of
      synaptic weight and age. Furthermore, we show that the PF-PC synapse is able to
      sustain transmission at very high frequencies for tens of stimuli, as a result of
      accelerated vesicle replenishment and an apparent recruitment of release site
      vesicles, which appears to be a central mechanism of paired-pulse facilitation at
      this synapse. These properties ensure that PF-PC synapses possess a dynamic range
      enabling the temporal code of MF inputs to be transmitted reliably to the PC.

PMID- 22378896
TI  - Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene
      influences fMRI signal responses during emotional stimulus processing.
AB  - The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and
      behavioral responses to stress and has been implicated in the development of
      major depressive disorder (MDD). Recent reports suggest that GG-homozygous
      individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1
      (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability.
      The present study explores whether those observations extend to the neuronal
      processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and
      a preliminary sample of 16 unmedicated patients with MDD who completed a
      functional magnetic resonance imaging scan while viewing blocks of positive,
      negative, and neutral words. In addition, potential mediating factors such as
      early life stress, sex, personality traits, and negative memory bias were
      examined. Robust differences in blood oxygenation level-dependent (BOLD) signal
      were found in healthy controls (A allele carriers > GG-homozygotes) in the right
      middle temporal/angular gyrus while subjects were viewing negative versus neutral
      words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater
      in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A
      carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50)
      in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life
      stress, personality traits, and levels of negative memory bias were associated
      with brain activity depending on genotype. Results from healthy controls and a
      preliminary sample of MDD participants show that CRHR1 single nucleotide
      polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting
      a potential mechanism of vulnerability for the development of MDD.

PMID- 22378897
TI  - Nicotinic receptor-mediated filtering of mitral cell responses to olfactory nerve
      inputs involves the alpha3beta4 subtype.
AB  - Acetylcholine (ACh) plays a major role in the processing of sensory inputs.
      Cholinergic input to the mammalian olfactory bulb modulates odor discrimination
      and perceptual learning by mechanisms that have yet to be elucidated. We have
      used the mouse olfactory bulb to examine the role of nicotinic ACh receptors
      (nAChRs) in regulating the responses of mitral cells (MCs), the output neurons of
      the olfactory bulb, to olfactory nerve input. We show that ACh activates
      alpha3beta4* nAChRs (* denotes the possible presence of other subunits) on MCs,
      leading to their excitation. Despite depolarizing MCs directly, the net effect of
      nAChR activation is to suppress olfactory nerve-evoked responses in these cells
      via activity-dependent feedback GABAergic mechanisms. Our results indicate that
      nAChRs gate incoming olfactory nerve input wherein weak input stimuli are
      filtered out, whereas strong stimuli are transmitted via the MCs. Based on our
      observations, we provide a mechanistic model for the sharpening of MC receptive
      fields by nAChRs, which could aid in odor discrimination and perceptual learning.

PMID- 22378899
TI  - Birth weight and neurocognition in schizophrenia spectrum disorders.
AB  - Low birth weight is associated with both schizophrenia and neurocognitive
      impairment. Yet, to our knowledge, no previous study has examined the
      relationship between lower birth weight and neurocognitive deficits in
      schizophrenia spectrum disorders (SSD). In this preliminary study, we
      investigated the relationship using a broad neuropsychological battery in cases
      with SSD and matched control subjects. The sample consisted of all subjects in
      the Developmental Insult and Brain Anomaly in Schizophrenia study, a nested case
      control investigation developed from a large birth cohort, which followed
      subjects longitudinally. Case ascertainment was based on computerized record
      linkages between the birth cohort members and the Kaiser Permanente Medical Care
      Plan, and all diagnoses were confirmed by consensus diagnosis following the
      Diagnostic Interview for Genetic Studies. Lower birth weight was associated with
      impairment in executive function, working memory, generalized intellectual
      function, and neuromotor function in cases with SSD but not in control subjects.
      No deficits were observed in verbal memory for either group. These results
      support the hypothesis that lower birth weight plays a role in neuropsychological
      disruptions in SSD and that the antecedents of lower birth weight may have a
      greater impact on these disruptions in SSD than in controls. These data may
      facilitate a better understanding of the etiopathogenesis of the cognitive
      underpinnings of SSD.

PMID- 22378900
TI  - New acquisition of antibiotic-resistant organisms in skilled nursing facilities.
AB  - The epidemiology of new acquisition of antibiotic-resistant organisms (AROs) in
      community-based skilled nursing facilities (SNFs) is not well studied. To define
      the incidence, persistence of, and time to new colonization with methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE),
      and ceftazidime-resistant (CAZ(r)) and ciprofloxacin-resistant (CIP(r)) Gram
      negative bacteria (GNB) in SNFs, SNF residents were enrolled and specimens from
      the nares, oropharynx, groin, perianal area, and wounds were prospectively
      cultured monthly. Standard microbiological tests were used to identify MRSA, VRE,
      and CAZ(r) and CIP(r) GNB. Residents with at least 3 months of follow-up were
      included in the analysis. Colonized residents were categorized as having either
      preexisting or new acquisition. The time to colonization for new acquisition of
      AROs was calculated. Eighty-two residents met the eligibility criteria. New
      acquisition of AROs was common. For example, of the 59 residents colonized with
      CIP(r) GNB, 28 (47%) were colonized with CIP(r) GNB at the start of the study
      (96% persistent and 4% intermittent), and 31 (53%) acquired CIP(r) GNB at the
      facility (61% persistent). The time to new acquisition was shortest for CIP(r)
      GNB, at a mean of 75.5 days; the time to new acquisition for MRSA was 126.6 days
      (P = 0.007 versus CIP(r) GNB), that for CAZ(r) was 176.0 days (P = 0.0001 versus
      CIP(r) GNB), and that for VRE was 186.0 days (P = 0.0004 versus CIP(r) GNB).
      Functional status was significantly associated with new acquisition of AROs (odds
      ratio [OR], 1.24; P = 0.01). New acquisition of AROs, in particular CIP(r) GNB
      and MRSA, is common in SNFs. CIP(r) GNB are acquired rapidly. Additional
      longitudinal studies to investigate risk factors for ARO acquisition are
      required.

PMID- 22378901
TI  - Prediction system for rapid identification of Salmonella serotypes based on
      pulsed-field gel electrophoresis fingerprints.
AB  - A classification model is presented for rapid identification of Salmonella
      serotypes based on pulsed-field gel electrophoresis (PFGE) fingerprints. The
      classification model was developed using random forest and support vector machine
      algorithms and was then applied to a database of 45,923 PFGE patterns, randomly
      selected from all submissions to CDC PulseNet from 2005 to 2010. The patterns
      selected included the top 20 most frequent serotypes and 12 less frequent
      serotypes from various sources. The prediction accuracies for the 32 serotypes
      ranged from 68.8% to 99.9%, with an overall accuracy of 96.0% for the random
      forest classification, and ranged from 67.8% to 100.0%, with an overall accuracy
      of 96.1% for the support vector machine classification. The prediction system
      improves reliability and accuracy and provides a new tool for early and fast
      screening and source tracking of outbreak isolates. It is especially useful to
      get serotype information before the conventional methods are done. Additionally,
      this system also works well for isolates that are serotyped as "unknown" by
      conventional methods, and it is useful for a laboratory where standard serotyping
      is not available.

PMID- 22378902
TI  - First report of infectious pericarditis due to Bordetella holmesii in an adult
      patient with malignant lymphoma.
AB  - Bordetella holmesii is a fastidious Gram-negative rod first identified in 1995.
      Though rare, it is isolated mainly in immunocompromised and asplenic hosts and is
      associated with bacteremia, pertussis-like respiratory tract infection, and
      endocarditis. Herein, we describe a unique B. holmesii infectious pericarditis
      patient with malignant lymphoma.

PMID- 22378903
TI  - Mixed tuberculosis infections in rural South Vietnam.
AB  - Tuberculosis patients may be infected with or have disease caused by more than
      one Mycobacterium tuberculosis strain, usually referred to as "mixed infections."
      These have mainly been observed in settings with a very high tuberculosis
      incidence and/or high HIV prevalence. We assessed the rate of mixed infections in
      a population-based study in rural Vietnam, where the prevalences of both HIV and
      tuberculosis are substantially lower than those in previous studies looking at
      mixed infections. In total, 1,248 M. tuberculosis isolates from the same number
      of patients were subjected to IS6110 restriction fragment length polymorphism
      (RFLP) typing, spoligotyping, and variable-number-tandem-repeat (VNTR) typing. We
      compared mixed infections identified by the presence of (i) discrepant RFLP and
      spoligotype patterns in isolates from the same patient and (ii) double alleles at
      >= 2 loci by VNTR typing and assessed epidemiological characteristics of these
      infections. RFLP/spoligotyping and VNTR typing identified 39 (3.1%) and 60 (4.8%)
      mixed infections, respectively (Cohen's kappa statistic, 0.57). The number of
      loci with double alleles in the VNTR pattern was strongly associated with the
      proportion of isolates with mixed infections according to RFLP/spoligotyping (P <
      0.001). Mixed infections occurred more frequently in newly treated than in
      previously treated patients, were significantly associated with minor X-ray
      abnormalities, and were almost significantly associated with lower sputum smear
      grades. Although the infection pressure in our study area is lower than that in
      previously studied populations, mixed M. tuberculosis infections do occur in
      rural South Vietnam in at least 3.1% of cases.

PMID- 22378904
TI  - Development of a novel genus-specific real-time PCR assay for detection and
      differentiation of Bartonella species and genotypes.
AB  - The genus Bartonella includes numerous species with varied host associations,
      including several that infect humans. Development of a molecular diagnostic
      method capable of detecting the diverse repertoire of Bartonella species while
      maintaining genus specificity has been a challenge. We developed a novel real
      time PCR assay targeting a 301-bp region of the ssrA gene of Bartonella and
      demonstrated specific amplification in over 30 Bartonella species, subspecies,
      and strains. Subsequent analysis of ssrA sequences was sufficient to discriminate
      Bartonella species and provided phylogenetic data consistent with that of gltA, a
      commonly used gene for differentiating Bartonella genotypes. Using this assay, we
      identified Bartonella DNA in 29% and 47% of blood specimens from elk in Wyoming
      and cattle in the Republic of Georgia, respectively. Sequence analysis of a
      subset of genotypes from elk specimens revealed a cluster most closely related to
      Bartonella capreoli, and genotypes from cattle were identified as Bartonella
      bovis, both Bartonella species commonly found in wild and domestic ruminants.
      Considering the widespread geographic distribution and infectivity potential to a
      variety of hosts, this assay may be an effective diagnostic method for
      identification of Bartonella infections in humans and have utility in Bartonella
      surveillance studies.

PMID- 22378905
TI  - Diagnostic strategy for identifying avian pathogenic Escherichia coli based on
      four patterns of virulence genes.
AB  - In order to improve the identification of avian pathogenic Escherichia coli
      (APEC) strains, an extensive characterization of 1,491 E. coli isolates was
      conducted, based on serotyping, virulence genotyping, and experimental
      pathogenicity for chickens. The isolates originated from lesions of avian
      colibacillosis (n = 1,307) or from the intestines of healthy animals (n = 184)
      from France, Spain, and Belgium. A subset (460 isolates) of this collection was
      defined according to their virulence for chicks. Six serogroups (O1, O2, O5, O8,
      O18, and O78) accounted for 56.5% of the APEC isolates and 22.5% of the
      nonpathogenic isolates. Thirteen virulence genes were more frequently present in
      APEC isolates than in nonpathogenic isolates but, individually, none of them
      could allow the identification of an isolate as an APEC strain. In order to take
      into account the diversity of APEC strains, a statistical analysis based on a
      tree-modeling method was therefore conducted on the sample of 460 pathogenic and
      nonpathogenic isolates. This resulted in the identification of four different
      associations of virulence genes that enables the identification of 70.2% of the
      pathogenic strains. Pathogenic strains were identified with an error margin of
      4.3%. The reliability of the link between these four virulence patterns and
      pathogenicity for chickens was validated on a sample of 395 E. coli isolates from
      the collection. The genotyping method described here allowed the identification
      of more APEC isolates with greater reliability than the classical serotyping
      methods currently used in veterinary laboratories.

PMID- 22378906
TI  - mecA-positive Staphylococcus aureus with low-level oxacillin MIC in Taiwan.
AB  - Although the presence of mecA is the genotypic determinant of methicillin
      resistant Staphylococcus aureus (MRSA), certain MRSA strains, especially
      community-associated MRSA (C-MRSA), can display an oxacillin MIC in the Clinical
      and Laboratory Standards Institute susceptible breakpoint range (<= 2 MUg/ml).
      Among 91 and 180 isolates thought to be methicillin-susceptible S. aureus (MSSA)
      with oxacillin MICs of 2 and 1 MUg/ml as determined by the Sensititre broth
      microdilution test initially, 52 (57.1%) and 6 (3.3%), respectively, were mecA
      positive. These mecA-positive low-oxacillin-MIC isolates belong to the dominant
      Taiwan C-MRSA clone (clonal complex [CC] 59), 56 of which carried SCCmec type V
      and were pvl positive, and 43 of which belonged to spa CC t437. All 271 isolates
      were retested by Sensititre, as well as by Vitek II and disk diffusion (DD).
      Based on the oxacillin results, the sensitivities of the Sensititre, Vitek II,
      and DD methods were 48.3% (28/58), 46.6% (27/58), and 89.6% (52/58),
      respectively. Although cefoxitin was better at detecting these isolates, 12.1,
      10.4, and 5.2% of these isolates were still misidentified as MSSA by Sensititre,
      Vitek II, and DD, respectively. These results highlight the difficulty in the
      accurate identification of MRSA with borderline oxacillin MICs in the CC59:SCCmec
      V clone, which likely has contributed to its spread in the health care and
      community settings. Since this clone has now been detected in other countries,
      and since other C-MRSA lineages have also been found to have low-level beta
      lactam resistance, the findings of the present study may be relevant to other
      regions. Further studies are warranted to determine the extent and clinical
      impact of such misidentification.

PMID- 22378907
TI  - Real-time molecular epidemiology of tuberculosis by direct genotyping of smear
      positive clinical specimens.
AB  - We applied MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number
      tandem-repeat typing) to directly analyze the bacilli present in 61 stain
      positive specimens from tuberculosis patients. A complete MIRU type (24 loci) was
      obtained for all but one (no amplification in one locus) of the specimens
      (98.4%), and the allelic values fully correlated with those obtained from the
      corresponding cultures. Our study is the first to demonstrate that real-time
      genotyping of Mycobacterium tuberculosis can be achieved, fully transforming the
      way in which molecular epidemiology techniques can be integrated into control
      programs.

PMID- 22378908
TI  - Evaluation of the Cepheid Xpert Flu Assay for rapid identification and
      differentiation of influenza A, influenza A 2009 H1N1, and influenza B viruses.
AB  - The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification
      system that provides multiplexed PCR detection of the influenza A, influenza A
      2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on
      time. Six laboratories participated in a clinical trial comparing the results of
      the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with
      archived and prospectively collected nasal aspirate-wash (NA-W) specimens and
      nasopharyngeal (NP) swabs from children and adults. Discrepant results were
      resolved by DNA sequence analysis. After discrepant-result analysis, the
      sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing
      the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those
      of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of
      the assay for prospective NP swabs compared to those of culture were 100%, 100%,
      and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA
      W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A,
      influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%,
      respectively, while the sensitivities of the Xpert Flu Assay for archived NP
      swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The
      sensitivities of the Xpert Flu Assay with archived NP specimens compared to those
      of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We
      conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is
      suitable for on-demand testing for influenza viral infection.

PMID- 22378909
TI  - Multisite performance evaluation of an enzyme-linked immunosorbent assay for
      detection of Giardia, Cryptosporidium, and Entamoeba histolytica antigens in
      human stool.
AB  - A novel fecal antigen detection assay for fresh and frozen human samples that
      detects but does not differentiate Giardia spp, Cryptosporidium spp, and
      Entamoeba histolytica, the Tri-Combo parasite screen, was compared to three
      established enzyme-linked immunosorbent assays (ELISAs) at three international
      sites. It exhibited 97.9% sensitivity and 97.0% specificity, with positive and
      negative predictive values of 93.4% and 99.1%, respectively. The Tri-Combo test
      proved a reliable means to limit the use of individual parasite ELISAs to
      positive samples.

PMID- 22378910
TI  - Detection of resistance to second-line antituberculosis drugs by use of the
      genotype MTBDRsl assay: a multicenter evaluation and feasibility study.
AB  - The rate of multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      tuberculosis (TB) has been steadily increasing in countries of the former USSR.
      The availability of rapid and reliable methods for the detection of drug
      resistance to second-line drugs is vital for adequate patient management. We
      evaluated the performance of the Genotype MTBDRsl assay compared to that of
      phenotypic drug susceptibility testing (Becton Dickinson Bactec MGIT 960 system)
      with a test panel of 200 Mycobacterium tuberculosis isolates at four sites in
      Eastern Europe. The interpretability of the Genotype MTBDRsl assay was over 95%.
      The sensitivity for the detection of resistance to fluoroquinolones, ethambutol,
      amikacin, and capreomycin varied between 77.3% and 92.3%; however, it was much
      lower for kanamycin (42.7%). The sensitivity for the detection of XDR TB was
      22.6%. The test specificity was over 82% for all drugs. The assay presents a good
      screening tool for the rapid detection of resistance to individual second-line
      drugs and can be recommended for use in countries with a high burden of MDR/XDR
      TB. The sensitivity for the detection of kanamycin resistance needs improvement.

PMID- 22378911
TI  - Dimethyl sulfoxide enhances effectiveness of skin antiseptics and reduces
      contamination rates of blood cultures.
AB  - Effective skin antisepsis is of central importance in the prevention of wound
      infections, colonization of medical devices, and nosocomial transmission of
      microorganisms. Current antiseptics have a suboptimal efficacy resulting in
      substantial infectious morbidity, mortality, and increased health care costs.
      Here, we introduce an in vitro method for antiseptic testing and a novel alcohol
      based antiseptic containing 4 to 5% of the polar aprotic solvent dimethyl
      sulfoxide (DMSO). The DMSO-containing antiseptic resulted in a 1- to 2-log
      enhanced killing of Staphylococcus epidermidis and other microbes in vitro
      compared to the same antiseptic without DMSO. In a prospective clinical
      validation, blood culture contamination rates were reduced from 3.04% for 70%
      isopropanol-1% iodine (control antiseptic) to 1.04% for 70% isopropanol-1% iodine
      5% DMSO (P < 0.01). Our results predict that improved skin antisepsis is possible
      using new formulations of antiseptics containing strongly polarized but
      nonionizing (polar aprotic) solvents.

PMID- 22378912
TI  - Novel genetic variation identified at fixed loci in ORF62 of the Oka varicella
      vaccine and in a case of vaccine-associated herpes zoster.
AB  - The live attenuated Oka varicella vaccine (vOka), derived from clade 2 wild-type
      (wt) virus pOka, is used for routine childhood immunization in several countries,
      including the United States, which has caused dramatic declines in the incidence
      of varicella. vOka can cause varicella, establish latency, and reactivate to
      cause herpes zoster (HZ). Three loci in varicella-zoster virus (VZV) open reading
      frame 62 (ORF62) (106262, 107252, and 108111) are used to distinguish vOka from
      wt VZV. A fourth position (105705) is also fixed for the vOka allele in nearly
      all vaccine batches. These 4 positions and two vOka mutations (106710 and 107599)
      reportedly absent from Varivax were analyzed on Varivax-derived ORF62 TOPO TA
      clones. The wt allele was detected at positions 105705 and 107252 on 3% and 2% of
      clones, respectively, but was absent at positions 106262 and 108111. Position
      106710 was fixed for the wt allele, whereas the vOka allele was present on 18.4%
      of clones at position 107599. We also evaluated the 4 vOka markers in an isolate
      obtained from a case of vaccine-caused HZ. The isolate carried the vOka allele at
      positions 105705, 106262, and 108111. However, at position 107252, the wt allele
      was present. Thus, all of the ORF62 vOka markers previously regarded as fixed
      occur as the wt allele in a small percentage of vOka strains. Characterization of
      all four vOka markers in ORF62 and of the clade 2 subtype marker in ORF38 is now
      necessary to confirm vOka adverse events.

PMID- 22378914
TI  - Performance of the Abbott RealTime and Roche Cobas TaqMan hepatitis C virus (HCV)
      assays for quantification of HCV genotypes.
AB  - We evaluated the Abbott RealTime (ART) and Roche Cobas TaqMan Hepatitis C virus
      (HCV) viral load assays for quantification of HCV genotypes in patient specimens.
      The ART HCV assay was a more sensitive and precise tool for accurate HCV viral
      load quantification across the HCV genotypes tested, especially genotype 1b.

PMID- 22378913
TI  - Streptococcus pseudopneumoniae identification by pherotype: a method to assist
      understanding of a potentially emerging or overlooked pathogen.
AB  - The recent identification of Streptococcus pseudopneumoniae (pseudopneumococcus)
      has complicated classification schemes within members of the "mitis"
      streptococcal group. Accurate differentiation of this species is necessary for
      understanding its disease potential and identification in clinical settings. This
      work described the use of the competence-stimulatory peptide ComC sequence for
      identification of S. pseudopneumoniae. ComC sequences from clinical sources were
      determined for 17 strains of S. pseudopneumoniae, Streptococcus pneumoniae, and
      Streptococcus oralis. An additional 58 ComC sequences from a range of sources
      were included to understand the diversity and suitability of this protein as a
      diagnostic marker for species identification. We identified three pherotypes for
      this species, delineated CSP6.1 (10/14, 79%), CSP6.3 (3/14, 21%), and SK674
      (1/14, 7%). Pseudopneumococcal ComC sequences formed a discrete cluster within
      those of other oral streptococci. This suggests that the comC sequence could be
      used to identify S. pseudopneumoniae, thus simplifying the study of the
      pathogenic potential of this organism. To avoid confusion between pneumococcal
      and pseudopneumococcal pherotypes, we have renamed the competence pherotype
      CSP6.1, formerly reported as an "atypical" pneumococcus, CSPps1 to reflect its
      occurrence in S. pseudopneumoniae.

PMID- 22378915
TI  - Ultrarapid detection of blaKPC1/2-12 from perirectal and nasal swabs by use of
      real-time PCR.
AB  - The novel real-time PCR assay developed as described here was able to detect
      bla(KPC1/2-12) (bla(KPC-1/2) to bla(KPC-12)) from easily available clinical
      specimens in less than 2 h. The genotypic assay was highly sensitive (100%) and
      specific (98%). In some cases, it was able to detect bla(KPC) 48 h before
      positive detection by standard phenotypic assay on patients who were monitored
      daily. The high sensitivity and rapidity of the molecular method make it the
      method of choice for KPC surveillance and, thus, containment purposes.

PMID- 22378916
TI  - Regional differences in incidence and patient characteristics of moyamoya
      disease: a systematic review.
AB  - BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare cause of stroke,
      initially described in Japan. In other countries, incidences and presenting
      symptoms may differ from those in Japan. The literature on regional differences
      in incidence and patient characteristics of MMD was systematically reviewed.
      METHODS: Medline, EMBASE and CINAHL were searched for population based studies on
      MMD published between January 1969 and January 2011. From studies that met
      predefined inclusion criteria, information was extracted on incidence and patient
      characteristics. Incidences with corresponding 95% CIs if possible were
      calculated and descriptive statistics for patient characteristics were used.
      RESULTS: 8 studies were included: three from Japan, one each from Taiwan and
      China and three from the USA. Incidences per 100 000 patient years ranged in
      Japan from 0.35 to 0.94 (95% CI 0.69 to 1.19), in the USA from 0.05 (-0.04 to
      0.12) in Iowa to 0.17 (-0.06 to 0.40) in Hawaii and were 0.41 (0.28 to 0.54) in
      Nanjing, China and 0.02 (0.003 to 0.04) in Taiwan. Female to male ratio ranged
      from 1.1 (0.9 to 1.5) in Nanjing to 2.8 (1.2 to 6.1) in Iowa. Proportions with
      intracerebral haemorrhage as the initial presentation were 56% in China, 52% in
      Taiwan, 29% in Hawaii, 21% in Japan and 10% in Iowa. Patients with childhood
      onset presented most often with ischaemia (>75%) in all regions. CONCLUSIONS: MMD
      incidence was higher in Japan and China than in Taiwan and North America and
      presenting symptoms showed regional differences, which are thus far unexplained.
      Population based data on MMD in Europe are lacking.

PMID- 22378917
TI  - Thrombolytic therapy for ischaemic stroke in patients using warfarin: a
      systematic review and meta-analysis.
AB  - BACKGROUND: It is uncertain whether thrombolytic therapy is safe in patients with
      acute ischaemic stroke who are treated with warfarin and have a subtherapeutic
      international normalised ratio (INR) at stroke onset. METHODS: The authors
      performed a systematic review of the literature and included studies that
      assessed the relation between prior warfarin use with subtherapeutic INR and
      outcome after intravenous or intra-arterial thrombolytic therapy in acute
      ischaemic stroke. Outcome measures were symptomatic intracranial haemorrhage
      (SICH), modified Rankin scale score 0-2 and mortality. Second, the authors
      performed a meta-analysis of the included studies. RESULTS: Seven studies with
      3631 patients were included. 240 (6.6%) patients used warfarin before stroke
      onset. The risk of SICH was increased in the warfarin group (OR 2.6; 95% CI 1.1
      to 5.9. p=0.02). There was no significant difference, however, in functional
      outcome (OR 0.9; 95% CI 0.6 to 1.2, p=0.32) or death from all causes (OR 1.2; 95%
      CI 0.9 to 1.8). DISCUSSION: The risk of SICH after thrombolytic therapy is
      increased in patients using warfarin with subtherapeutic INR levels. The authors
      found no evidence of an increase in death from all causes or worsening of
      functional outcome in warfarin treated patients.

PMID- 22378918
TI  - Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb
      randomised sequential trial.
AB  - OBJECTIVES: To determine the safety and efficacy of lithium for the treatment of
      amyotrophic lateral sclerosis (ALS) in a randomised, placebo controlled, double
      blind, sequential trial. METHODS: Between November 2008 and June 2011, 133
      patients were randomised to receive lithium carbonate (target blood level 0.4-0.8
      mEq/l) or placebo as add-on treatment with riluzole. The primary endpoint was
      survival, defined as death, tracheostomal ventilation or non-invasive ventilation
      for more than 16 h/day. Secondary outcome measures consisted of the revised ALS
      Functional Rating Scale and forced vital capacity. Analysis was by intention to
      treat and according to a sequential trial design. RESULTS: 61 patients reached a
      primary endpoint, 33 of 66 in the lithium group and 28 of 67 patients in the
      placebo group. Lithium did not significantly affect survival (cumulative survival
      probability of 0.73 in the lithium group (95% CI 0.63 to 0.86) vs 0.75 in the
      placebo group (95% CI 0.65 to 0.87) at 12 months and 0.62 in the lithium group
      (95% CI 0.50 to 0.76) vs 0.67 in the placebo group (95% CI 0.56 to 0.81) at 16
      months). Secondary outcome measures did not differ between treatment groups. No
      major safety concerns were encountered. CONCLUSIONS: This trial, designed to
      detect a modest effect of lithium, did not demonstrate any beneficial effect on
      either survival or functional decline in patients with ALS. TRIAL REGISTRATION
      NUMBER: NTR1448. Name of trial registry: Lithium trial in ALS.

PMID- 22378919
TI  - Executive dysfunction in adults with moyamoya disease is associated with
      increased diffusion in frontal white matter.
AB  - BACKGROUND AND PURPOSE: Alteration of the cerebrovascular reserve (CVR) in the
      frontal lobes has been associated with cognitive dysfunction in adults with
      moyamoya disease (MMD). Elevation of the apparent diffusion coefficient (ADC) in
      normal-appearing white matter on conventional MRI may occur as a consequence of
      chronic haemodynamic failure. In the present study, the authors examined the
      relation of ADC with CVR and cognitive dysfunction in adults with MMD. METHODS:
      The authors measured ADC and CVR in the normal-appearing frontal white matter.
      CVR was calculated using dynamic susceptibility contrast-enhanced MRI and the
      acetazolamide challenge. A standardised and validated neuropsychological
      assessment test battery focusing on executive function was used. RESULTS: 14
      patients, 9 women and 5 men (mean age 36.6+/-12.9 years), were included. The
      authors found executive dysfunction in 7 of 13 tested patients. ADC and CVR were
      negatively correlated (Spearman coefficient: -0.46; p=0.015). Elevation of ADC
      predicted executive dysfunction (area under receiver operating characteristic
      curve (95% CI): 0.85 (0.59 to 1.16); p=0.032). CONCLUSION: Elevation of ADC in
      the normal-appearing frontal white matter of adults with MMD was associated with
      reduced CVR and executive dysfunction. This preliminary study suggests that
      measurement of ADC might be used to detect patients at risk for cerebral
      ischaemia and cognitive impairment.

PMID- 22378920
TI  - Adrenarche in nonhuman primates: the evidence for it and the need to redefine it.
AB  - Adrenarche is most commonly defined as a prepubertal increase in circulating
      adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS).
      This event is thought to have evolved in humans and some great apes but not in
      Old World monkeys, perhaps to promote brain development. Whether adrenarche
      represents a shared, derived developmental event in humans and our closest
      relatives, adrenal androgen secretion (and its regulation) is of considerable
      clinical interest. Specifically, adrenal androgens play a significant role in the
      pathophysiology of polycystic ovarian disease and breast and prostate cancers.
      Understanding the development of androgen secretion by the human adrenal cortex
      and identifying a suitable model for its study are therefore of central
      importance for clinical and evolutionary concerns. This review will examine the
      evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader
      definition of this developmental event is needed, including morphological,
      biochemical, and endocrine criteria. Using such a definition, evidence from
      recent studies suggests that adrenarche evolved in Old World primates but spans a
      relatively brief period early in development compared with humans and some great
      apes. This emphasizes the need for frequent longitudinal sampling in evaluating
      developmental changes in adrenal androgen secretion as well as the tenuous nature
      of existing evidence of adrenarche in some species among the great apes. Central
      to an understanding of the regulation of adrenal androgen production in humans is
      the recognition of the complex nature of adrenarche and the need for more
      carefully conducted comparative studies and a broader definition in order to
      promote investigation among NHP in particular.

PMID- 22378921
TI  - beta (CCL2) and alpha (CXCL10) chemokine modulations by cytokines and peroxisome
      proliferator-activated receptor-alpha agonists in Graves' ophthalmopathy.
AB  - No data are present in the literature about the effect of cytokines on the
      prototype beta chemokine (C-C motif) ligand 2 (CCL2) or of peroxisome
      proliferator-activated receptor alpha (PPARalpha (PPARA)) activation on CCL2 and
      CXCL10 chemokines secretion in fibroblasts or preadipocytes in Graves'
      ophthalmopathy (GO). We have tested the effect of interferon gamma (IFNgamma
      (IFNG)) and tumor necrosis factor alpha (TNFalpha) on CCL2, and for comparison on
      the prototype alpha chemokine (C-X-C motif) ligand 10 (CXCL10), and the possible
      modulatory role of PPARalpha activation on secretion of these chemokines in
      normal and GO fibroblasts or preadipocytes in primary cell cultures. This study
      shows that IFNgamma alone, or in combination with TNFalpha, stimulates the
      secretion of CCL2 in primary orbital fibroblasts or preadipocytes from patients
      with GO at levels similar to those observed in controls. IFNgamma and TNFalpha
      also stimulated CXCL10 chemokine secretion as expected. The presence of PPARalpha
      and PPARgamma (PPARG) in primary fibroblasts or preadipocytes of patients with GO
      has been confirmed. PPARalpha activators were able to inhibit the secretion of
      CXCL10 and CCL2, while PPARgamma activators were confirmed to be able to inhibit
      CXCL10 but had no effect on CCL2. PPARalpha activators were stronger inhibitors
      of chemokine secretions than PPARgamma agonists. In conclusion, CCL2 and CXCL10
      are modulated by IFNgamma and TNFalpha in GO. PPARalpha activators inhibit the
      secretion of the main prototype alpha (CXCL10) and beta (CCL2) chemokines in GO
      fibroblasts or preadipocytes, suggesting that PPARalpha may be involved in the
      modulation of the immune response in GO.

PMID- 22378922
TI  - CD4+ T cells and HIV: A paradoxical Pas de Deux.
AB  - When it comes to HIV infection, CD4(+) T cells are usually thought of as the
      cells that are preferentially infected and killed by the virus. In a new study,
      Soghoian et al. now show that during the early stages of HIV infection, CD4(+) T
      cells suppress virus replication and delay disease onset. Thus, the robustness of
      the CD4(+) T cell response during early HIV infection could be used as a marker
      to determine the speed of disease progression. The new findings also have
      implications for the design of preventive and therapeutic AIDS vaccines.

PMID- 22378923
TI  - Toward a meningitis-free world.
AB  - Meningococcal meningitis is a devastating disease that is often fatal. Vaccines
      against the five major meningococcal serogroups causing disease are about to
      become available, a conjugate vaccine against meningococcus A is in use for mass
      vaccination in Africa, and a protein-based vaccine against meningococcal B is
      ready for licensure. With the availability of these new vaccines, the world can
      finally be rid of meningococcal meningitis, thus rewriting a new chapter in
      medical history.

PMID- 22378924
TI  - Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase.
AB  - Ebola virus causes a fulminant infection in humans resulting in diffuse bleeding,
      vascular instability, hypotensive shock, and often death. Because of its high
      mortality and ease of transmission from human to human, Ebola virus remains a
      biological threat for which effective preventive and therapeutic interventions
      are needed. An understanding of the mechanisms of Ebola virus pathogenesis is
      critical for developing antiviral therapeutics. Here, we report that productive
      replication of Ebola virus is modulated by the c-Abl1 tyrosine kinase. Release of
      Ebola virus-like particles (VLPs) in a cell culture cotransfection system was
      inhibited by c-Abl1-specific small interfering RNA (siRNA) or by Abl-specific
      kinase inhibitors and required tyrosine phosphorylation of the Ebola matrix
      protein VP40. Expression of c-Abl1 stimulated an increase in phosphorylation of
      tyrosine 13 (Y(13)) of VP40, and mutation of Y(13) to alanine decreased the
      release of Ebola VLPs. Productive replication of the highly pathogenic Ebola
      virus Zaire strain was inhibited by c-Abl1-specific siRNAs or by the Abl-family
      inhibitor nilotinib by up to four orders of magnitude. These data indicate that c
      Abl1 regulates budding or release of filoviruses through a mechanism involving
      phosphorylation of VP40. This step of the virus life cycle therefore may
      represent a target for antiviral therapy.

PMID- 22378927
TI  - It's good not to talk.

PMID- 22378926
TI  - A biophysical indicator of vaso-occlusive risk in sickle cell disease.
AB  - The search for predictive indicators of disease has largely focused on molecular
      markers. However, biophysical markers, which can integrate multiple pathways, may
      provide a more global picture of pathophysiology. Sickle cell disease affects
      millions of people worldwide and has been studied intensely at the molecular,
      cellular, tissue, and organismal level for a century, but there are still few, if
      any, markers quantifying the severity of this disease. Because the complications
      of sickle cell disease are largely due to vaso-occlusive events, we hypothesized
      that a physical metric characterizing the vaso-occlusive process could serve as
      an indicator of disease severity. Here, we use a microfluidic device to
      characterize the dynamics of "jamming," or vaso-occlusion, in physiologically
      relevant conditions, by measuring a biophysical parameter that quantifies the
      rate of change of the resistance to flow after a sudden deoxygenation event. Our
      studies show that this single biophysical parameter could be used to distinguish
      patients with poor outcomes from those with good outcomes, unlike existing
      laboratory tests. This biophysical indicator could therefore be used to guide the
      timing of clinical interventions, to monitor the progression of the disease, and
      to measure the efficacy of drugs, transfusion, and novel small molecules in an ex
      vivo setting.

PMID- 22378925
TI  - HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict
      disease outcome.
AB  - Early immunological events during acute HIV infection are thought to
      fundamentally influence long-term disease outcome. Whereas the contribution of
      HIV-specific CD8 T cell responses to early viral control is well established, the
      role of HIV-specific CD4 T cell responses in the control of viral replication
      after acute infection is unknown. A growing body of evidence suggests that CD4 T
      cells-besides their helper function-have the capacity to directly recognize and
      kill virally infected cells. In a longitudinal study of a cohort of individuals
      acutely infected with HIV, we observed that subjects able to spontaneously
      control HIV replication in the absence of antiretroviral therapy showed a
      significant expansion of HIV-specific CD4 T cell responses-but not CD8 T cell
      responses-compared to subjects who progressed to a high viral set point (P =
      0.038). Markedly, this expansion occurred before differences in viral load or CD4
      T cell count and was characterized by robust cytolytic activity and expression of
      a distinct profile of perforin and granzymes at the earliest time point. Kaplan
      Meier analysis revealed that the emergence of granzyme A(+) HIV-specific CD4 T
      cell responses at baseline was highly predictive of slower disease progression
      and clinical outcome (average days to CD4 T cell count <350/MUl was 575 versus
      306, P = 0.001). These data demonstrate that HIV-specific CD4 T cell responses
      can be used during the earliest phase of HIV infection as an immunological
      predictor of subsequent viral set point and disease outcome. Moreover, these data
      suggest that expansion of granzyme A(+) HIV-specific cytolytic CD4 T cell
      responses early during acute HIV infection contributes substantially to the
      control of viral replication.

PMID- 22378929
TI  - Online marketing of medical procedures needs better regulation.

PMID- 22378930
TI  - Off the record.

PMID- 22378931
TI  - How can we treat multiple chronic conditions?

PMID- 22378932
TI  - Pioneers in promoting public health.

PMID- 22378933
TI  - Three people are evacuated from Homs as talks to secure a Syrian ceasefire
      flounder.

PMID- 22378934
TI  - Lifelong checks are needed for patients fitted with dangerous hip implants.

PMID- 22378935
TI  - Ductal carcinoma in situ of the breast.

PMID- 22378936
TI  - Multilevel and spatial analysis of syphilis in Shenzhen, China, to inform
      spatially targeted control measures.
AB  - OBJECTIVES: The present study investigates the varied spatial distribution of
      syphilis cases in Shenzhen, China, and explores the individual-, neighbourhood-
      and district-level factors affecting the distribution. METHODS: This study uses
      spatial analysis and multi-level generalised estimating equations to explore the
      spatial distribution of reported syphilis cases among individuals in Shenzhen,
      Guangdong Province, China. The spatial distribution of primary/secondary and
      latent cases was investigated using the Moran's I-statistic. Primary/secondary
      syphilis cases were compared with all syphilis cases using a three-level model
      with individual (n=6496), neighbourhood (n=55) and district (n=6) levels.
      RESULTS: A total of 6496 syphilis cases were reported in 2009 with 35.8% primary
      and secondary syphilis cases. Both primary/secondary syphilis cases (Moran's I
      value=0.33, p<0.01) and latent syphilis cases (Moran's I value=0.19, p<0.01)
      showed significant spatial clustering at the neighbourhood level. Adjusting for
      the number of reporting hospitals, the best model found that the following
      characteristics were associated with primary/secondary syphilis infection:
      individuals who are younger in age (p=0.003), male (p<0.001), migrant labourers
      (p=0.047) and those who live in districts with a higher gross domestic product
      (p<0.001). CONCLUSIONS: There is substantial clustering of primary and secondary
      syphilis cases at the neighbourhood level in Shenzhen, suggesting the need for
      greater STD health service provision in these clustered neighbourhoods. Spatially
      targeted syphilis control measures may be useful to optimise testing, treatment
      and partner services.

PMID- 22378937
TI  - Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2
      chemokine receptor, for the treatment of type 2 diabetes and associated
      complications.
AB  - The following manuscript was published as a Fast Forward article on February 29,
      2012: Sullivan TJ, Dairaghi DJ, Krasinski A, Miao Z, Wang Y, Zhao BN, Baumgart T,
      Berahovich R, Ertl LS, Pennell A, Seitz L, Miao S, Ungashe S, Wei Z, Johnson D,
      Boring L, Tsou C-L, Charo IF, Bekker P, Schall TJ, and Jaen JC, Characterization
      of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor,
      for the treatment of type 2 diabetes and associated complications. J Pharmacol
      Exp Ther jpet.111.190918; doi:10.1124/jpet.111.190918 It was later found that the
      chemical identity of a compound cited in the article, CCX140-B, was not
      sufficiently disclosed. The authors are unable, at this time, to provide the
      chemical identity of CCX140-B in accordance with the editorial policies of The
      Journal of Pharmacology and Experimental Therapeutics. As a result, the authors
      have voluntarily withdrawn this manuscript from publication. We apologize for any
      inconvenience this may cause JPET's readers.

PMID- 22378938
TI  - Modeling disease progression and rosiglitazone intervention in type 2 diabetic
      Goto-Kakizaki rats.
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of rosiglitazone were studied
      in type 2 diabetic (T2D) Goto-Kakizaki (GK) rats that received daily doses of 0,
      5, or 10 mg/kg for 23 days followed by 60 days of washout. Blood glucose, plasma
      insulin, and hemoglobin A1c were determined over time. Oral glucose tolerance
      tests were performed before and at the end of treatment and after 20 days of
      washout to determine insulin sensitivity and beta-cell function. Rosiglitazone
      effectively lowered glucose by inhibiting hepatic glucose production and
      enhancing insulin sensitivity. The glucose-insulin inter-regulation was
      characterized by a feedback model: glucose and insulin have their own production
      (k(in)) and elimination (k(out)) rate constants, whereas glucose stimulates
      insulin production (k(inI)) and insulin, in turn, promotes glucose utilization
      (k(outG)). Animal handling and placebo treatment affected glucose turnover with
      k(pl) = 0.388 kg/mg/day. The PK of rosiglitazone was fitted with a one
      compartment model with first-order absorption. The effect of rosiglitazone was
      described as inhibition of k(inG) with I(max) = 0.296 and IC(50) = 1.97 MUg/ml.
      Rosiglitazone also stimulated glucose utilization by improving insulin
      sensitivity with a linear factor S(R) = 0.0796 kg/mg. In GK rats, 23 days of
      treatment increased body weight but did not cause hemodilution. Weight gain was
      characterized with body weight input (k(s)(w)) and output (k(d)(w)), and
      rosiglitazone inhibited k(d)(w) with ID(50) = 96.8 mg/kg. The mechanistic PK/PD
      model quantitatively described the glucose-insulin system and body weights under
      chronic rosiglitazone treatment in T2D rats.

PMID- 22378939
TI  - Right of disabled people to independent living are threatened by government's
      reforms, MPs and peers say.

PMID- 22378940
TI  - Pattern of cancer deaths in a saudi tertiary care hospital.
AB  - The medical records of deceased patients were reviewed to describe the pattern of
      cancer deaths in a newly established Saudi tertiary care hospital. During eleven
      months, 87 patients died of cancer. The majority (80 patients, 92%) died of
      incurable cancer; among which 53% did not receive any systemic anti-cancer
      therapy (SAT) and 43% received SAT with palliative intent. Younger age (< 65
      years), relatively chemosensitive tumours and initial presentation in a
      potentially curable stage were associated with higher prevalence of palliative
      SAT administration (p = 0.009, 0.019 and 0.001, respectively). The last
      palliative SAT was administered during the last two months of life in 66% and
      during the last two weeks in 14%. During the last admission, 54% of patients were
      admitted through emergency room, 50% stayed >14 days and 14% died in intensive
      care unit or emergency room. The results demonstrate that palliative care is a
      realistic treatment for the majority of patients in our setting and that a
      significant proportion of these patients receive aggressive care at the end-of
      life. There is a need to establish an integrative palliative care program to
      improve the quality-of-life of dying cancer patients in our region and to
      minimize the aggressiveness of end-of-life care.

PMID- 22378941
TI  - Mortality among active-duty male French Armed Forces, 2006-10.
AB  - BACKGROUND: In the Armed Forces, knowledge about the causes of deaths is required
      in order to develop prevention strategies. This study presents the main
      characteristics of causes of deaths among male active-duty personnel in the
      French Armed Forces during the 2006-10 period and compares them with the general
      French male population. METHODS: The data are provided by military public health
      surveillance. Comparisons of the specific mortality rates (MR) were performed
      using a Poisson regression. Standardized mortality ratios (SMRs) were calculated
      to compare mortality with the general French male population. RESULTS: There were
      1455 deaths among male active-duty personnel during the study period [MR: 100.9
      per 100,000 person-years (PY); 95% confidence interval 95.7-106.1]. The 17-24 age
      group was characterized by violent deaths: transport accident (MR: 45.9 per
      100,000 PY) and suicide (18.8 per 100 000 PY). Overall SMRs show significantly
      lower MR compared with the French national MR with the exception of SMR for
      transport accident and suicide in the 17-24 age group. CONCLUSIONS: There is a
      significantly lower deficit of mortality compared with the French male general
      population, reflecting a strong healthy worker effect. However, health promotion
      programmes should continue to put emphasis on transport accident especially among
      the 17-24 age group.

PMID- 22378942
TI  - Talking the talk, walking the walk: examining the effect of neighbourhood
      walkability and social connectedness on physical activity.
AB  - BACKGROUND: Few studies have considered the joint effects of social and physical
      environments on physical activity (PA). The primary purpose of this study was to
      examine the compounding effects of neighbourhood walkability and social
      connectedness on PA. METHODS: Data were collected from adults (n = 380) in
      Waterloo, Ontario, Canada. Perceptions of neighbourhood social connectedness and
      walkability were measured via survey. Minutes of neighbourhood PA for recreation
      and transportation were captured with a detailed 7-day log booklet. Four groups
      were created (e.g. high walkability/low social connectedness) and two factorial
      ANOVAs examined group differences in minutes of recreational and transport
      related PA. RESULTS: There were significant differences across the four
      walkability/social connectedness groups for both recreational (F = 11.36, P <
      0.01) and transport-related PA (F = 8.12, P < 0.01). Participants perceiving both
      high walkability and social connectedness displayed the greatest levels of both
      recreational (130.6 min) and transport-related PA (24.5 min). The high
      walkability/low social connectedness group had greater transport-related PA than
      the two low walkability groups, while the high social connectedness/low
      walkability group had greater recreational PA than the two low social
      connectedness groups. CONCLUSIONS: These findings underscore the relationship
      between physical and social dimensions of urban form and their association with
      health behaviours. PA promotion efforts should take into account both physical
      (e.g. land-use planning) and social (e.g. walking group) environments.

PMID- 22378943
TI  - Analysis of the arabinoxylan arabinofuranohydrolase gene family in barley does
      not support their involvement in the remodelling of endosperm cell walls during
      development.
AB  - Arabinoxylan arabinofuranohydrolases (AXAHs) are family GH51 enzymes that have
      been implicated in the removal of arabinofuranosyl residues from the (1,4)-beta
      xylan backbone of heteroxylans. Five genes encoding barley AXAHs range in size
      from 4.6 kb to 7.1 kb and each contains 16 introns. The barley HvAXAH genes map
      to chromosomes 2H, 4H, and 5H. A small cluster of three HvAXAH genes is located
      on chromosome 4H and there is evidence for gene duplication and the presence of
      pseudogenes in barley. The cDNAs corresponding to barley and wheat AXAH genes
      were cloned, and transcript levels of the genes were profiled across a range of
      tissues at different developmental stages. Two HvAXAH cDNAs that were
      successfully expressed in Nicotiana benthamiana leaves exhibited similar
      activities against 4-nitrophenyl alpha-L-arabinofuranoside, but HvAXAH2 activity
      was significantly higher against wheat flour arabinoxylan, compared with HvAXAH1.
      HvAXAH2 also displayed activity against (1,5)-alpha-L-arabinopentaose and
      debranched arabinan. Western blotting with an anti-HvAXAH antibody was used to
      define further the locations of the AXAH enzymes in developing barley grain,
      where high levels were detected in the outer layers of the grain but little or no
      protein was detected in the endosperm. The chromosomal locations of the genes do
      not correspond to any previously identified genomic regions shown to influence
      heteroxylan structure. The data are therefore consistent with a role for AXAH in
      depolymerizing arabinoxylans in maternal tissues during grain development, but do
      not provide compelling evidence for a role in remodelling arabinoxylans during
      endosperm or coleoptile development in barley as previously proposed.

PMID- 22378944
TI  - Two carbon fluxes to reserve starch in potato (Solanum tuberosum L.) tuber cells
      are closely interconnected but differently modulated by temperature.
AB  - Parenchyma cells from tubers of Solanum tuberosum L. convert several externally
      supplied sugars to starch but the rates vary largely. Conversion of glucose 1
      phosphate to starch is exceptionally efficient. In this communication, tuber
      slices were incubated with either of four solutions containing equimolar [U
      14C]glucose 1-phosphate, [U-14C]sucrose, [U-14C]glucose 1-phosphate plus
      unlabelled equimolar sucrose or [U-14C]sucrose plus unlabelled equimolar glucose
      1-phosphate. C14-incorporation into starch was monitored. In slices from freshly
      harvested tubers each unlabelled compound strongly enhanced 14C incorporation
      into starch indicating closely interacting paths of starch biosynthesis. However,
      enhancement disappeared when the tubers were stored. The two paths (and,
      consequently, the mutual enhancement effect) differ in temperature dependence. At
      lower temperatures, the glucose 1-phosphate-dependent path is functional,
      reaching maximal activity at approximately 20  degrees C but the flux of the
      sucrose-dependent route strongly increases above 20  degrees C. Results are
      confirmed by in vitro experiments using [U-14C]glucose 1-phosphate or adenosine
      [U-14C]glucose and by quantitative zymograms of starch synthase or phosphorylase
      activity. In mutants almost completely lacking the plastidial phosphorylase
      isozyme(s), the glucose 1-phosphate-dependent path is largely impeded.
      Irrespective of the size of the granules, glucose 1-phosphate-dependent
      incorporation per granule surface area is essentially equal. Furthermore, within
      the granules no preference of distinct glucosyl acceptor sites was detectable.
      Thus, the path is integrated into the entire granule biosynthesis. In vitro C14C
      incorporation into starch granules mediated by the recombinant plastidial
      phosphorylase isozyme clearly differed from the in situ results. Taken together,
      the data clearly demonstrate that two closely but flexibly interacting general
      paths of starch biosynthesis are functional in potato tuber cells.

PMID- 22378945
TI  - The 14-3-3 proteins of Arabidopsis regulate root growth and chloroplast
      development as components of the photosensory system.
AB  - The 14-3-3 proteins specifically bind a number of client proteins to influence
      important pathways, including flowering timing via the photosensory system. For
      instance, 14-3-3 proteins influence the photosensory system through interactions
      with Constans (CO) protein. 14-3-3 associations with the photosensory system were
      further studied in this investigation using 14-3-3 T-DNA insertion mutants to
      study root and chloroplast development. The 14-3-3 MU T-DNA insertion mutant, 14
      3-3MU-1, had shorter roots than the wild type and the difference in root length
      could be influenced by light intensity. The 14-3-3 nu T-DNA insertion mutants
      also had shorter roots, but only when grown under narrow-bandwidth red light.
      Five-day-old 14-3-3 T-DNA insertion and co mutants all had increased root
      greening compared with the wild type, which was influenced by light wavelength
      and intensity. However, beyond 10 d of growth, 14-3-3MU-1 roots did not increase
      in greening as much as wild-type roots. This study reveals new developmental
      roles of 14-3-3 proteins in roots and chloroplasts, probably via association with
      the photosensory system.

PMID- 22378946
TI  - Identification and evaluation of omega-3 fatty acid desaturase genes for
      hyperfortifying alpha-linolenic acid in transgenic rice seed.
AB  - alpha-Linolenic acid (ALA) deficiency and a skewed of omega6:omega3 fatty acid
      ratio in the diet are a major explanation for the prevalence of cardiovascular
      diseases and inflammatory/autoimmune diseases. There is a need to enhance the ALA
      content and to reduce the ratio of linoleic acid (LA) to ALA. Six omega-3 (Delta
      15) fatty acid desaturase (FAD) genes were cloned from rice and soybean. The
      subcellular localizations of the proteins were identified. The FAD genes were
      introduced into rice under the control of an endosperm-specific promoter, GluC,
      or a Ubi-1 promoter to evaluate their potential in increasing the ALA content in
      seeds. The ALA contents in the seeds of endoplasmic reticulum (ER)-localized
      GmFAD3-1 and OsFAD3 overexpression lines increased from 0.36 mg g-1 to 8.57 mg g
      1 and 10.06 mg g-1, respectively, which was 23.8- and 27.9-fold higher than that
      of non-transformants. The trait of high ALA content was stably inheritable over
      three generations. Homologous OsFAD3 is more active than GmFAD3-1 in catalysing
      LA conversion to ALA in rice seeds. Overexpression of ER-localized GmFAD3-2/3 and
      chloroplast-localized OsFAD7/8 had less effect on increasing the ALA content in
      rice seeds. The GluC promoter is advantageous compared with Ubi-1 in this
      experimental system. The enhanced ALA was preferentially located at the sn-2
      position in triacylglycerols. A meal-size portion of high ALA rice would meet
      >80% of the daily adult ALA requirement. The ALA-rich rice could be expected to
      ameliorate much of the global dietary ALA deficiency.

PMID- 22378948
TI  - Sporophytic ovule tissues modulate the initiation and progression of apomixis in
      Hieracium.
AB  - Apomixis in Hieracium subgenus Pilosella initiates in ovules when sporophytic
      cells termed aposporous initial (AI) cells enlarge near sexual cells undergoing
      meiosis. AI cells displace the sexual structures and divide by mitosis to form
      unreduced embryo sac(s) without meiosis (apomeiosis) that initiate fertilization
      independent embryo and endosperm development. In some Hieracium subgenus
      Pilosella species, these events are controlled by the dominant LOSS OF APOMEIOSIS
      (LOA) and LOSS OF PARTHENOGENESIS (LOP) loci. In H. praealtum and H.
      piloselloides, which both contain the same core LOA locus, the timing and
      frequency of AI cell formation is altered in derived mutants exhibiting abnormal
      funiculus growth and in transgenic plants expressing rolB which alters cellular
      sensitivity to auxin. The impact on apomictic and sexual reproduction was
      examined here when a chimeric RNAse gene was targeted to the funiculus and basal
      portions of the ovule, and also when polar auxin transport was inhibited during
      ovule development following N-1-naphthylphthalamic acid (NPA) application. Both
      treatments led to ovule deformity in the funiculus and distal parts of the ovule
      and LOA-dependent alterations in the timing, position, and frequency of AI cell
      formation. In the case of NPA treatment, this correlated with increased
      expression of DR5:GFP in the ovule, which marks the accumulation of the plant
      hormone auxin. Our results show that sporophytic information potentiated by
      funiculus growth and polar auxin transport influences ovule development, the
      initiation of apomixis, and the progression of embryo sac development in
      Hieracium. Signals associated with ovule pattern formation and auxin distribution
      or perception may influence the capacity of sporophytic ovule cells to respond to
      LOA.

PMID- 22378947
TI  - Evidence of a role for foliar salicylic acid in regulating the rate of post
      ingestive protein breakdown in ruminants and contributing to landscape pollution.
AB  - Ruminant farming is important to global food security, but excessive proteolysis
      in the rumen causes inefficient use of nitrogenous plant constituents and
      environmental pollution. While both plant and microbial proteases contribute to
      ruminal proteolysis, little is known about post-ingestion regulation of plant
      proteases except that activity in the first few hours after ingestion of fresh
      forage can result in significant degradation of foliar protein. As the signal
      salicylic acid (SA) influences cell death during both biotic and abiotic
      stresses, Arabidopsis wild-type and mutants were used to test the effect of SA on
      proteolysis induced by rumen conditions (39  degrees C and anaerobic in a neutral
      pH). In leaves of Col-0, SA accumulation was induced by exposure to a rumen
      microbial inoculum. Use of Arabidopsis mutants with altered endogenous SA
      concentrations revealed a clear correlation with the rate of stress-induced
      proteolysis; rapid proteolysis occurred in leaves of SA-accumulating mutants cpr5
      1 and dnd1-1 whereas there was little or no proteolysis in sid2-1 which is unable
      to synthesize SA. Reduced proteolysis in npr1-1 (Non-expressor of Pathogenesis
      Related genes) demonstrated a dependence on SA signalling. Slowed proteolysis in
      sid2-1 and npr1-1 was associated with the absence of a 34.6 kDa cysteine
      protease. These data suggest that proteolysis in leaves ingested by ruminants is
      modulated by SA. It is therefore suggested that influencing SA effects in planta
      could enable the development of forage crops with lower environmental impact and
      increased production potential.

PMID- 22378949
TI  - Insights into metabolic efficiency from flux analysis.
AB  - The efficiency of carbon and energy flows throughout metabolism defines the
      potential for growth and reproductive success of plants. Understanding the basis
      for metabolic efficiency requires relevant definitions of efficiency as well as
      measurements of biochemical functions through metabolism. Here insights into the
      basis of efficiency provided by (13)C-based metabolic flux analysis (MFA) as well
      as the uses and limitations of efficiency in predictive flux balance analysis
      (FBA) are highlighted. (13)C-MFA studies have revealed unusual features of
      central metabolism in developing green seeds for the efficient use of light to
      conserve carbon and identified metabolic inefficiencies in plant metabolism due
      to dissipation of ATP by substrate cycling. Constraints-based FBA has used
      efficiency to guide the prediction of the growth and actual internal flux
      distribution of plant systems. Comparisons in a few cases have been made between
      flux maps measured by (13)C-based MFA and those predicted by FBA assuming one or
      more maximal efficiency parameters. These studies suggest that developing plant
      seeds and photoautotrophic microorganisms may indeed have patterns of metabolic
      flux that maximize efficiency. MFA and FBA are synergistic toolsets for
      uncovering and explaining the metabolic basis of efficiencies and inefficiencies
      in plant systems.

PMID- 22378950
TI  - Iron uptake system mediates nitrate-facilitated cadmium accumulation in tomato
      (Solanum lycopersicum) plants.
AB  - Nitrogen (N) management is a promising agronomic strategy to minimize cadmium
      (Cd) contamination in crops. However, it is unclear how N affects Cd uptake by
      plants. Wild-type and iron uptake-inefficient tomato (Solanum lycopersicum)
      mutant (T3238fer) plants were grown in pH-buffered hydroponic culture to
      investigate the direct effect of N-form on Cd uptake. Wild-type plants fed NO3-
      accumulated more Cd than plants fed NH4+. Iron uptake and LeIRT1 expression in
      roots were also greater in plants fed NO3-. However, in mutant T3238fer which
      loses FER function, LeIRT1 expression in roots was almost completely terminated,
      and the difference between NO3- and NH4+ treatments vanished. As a result, the N
      form had no effect on Cd uptake in this mutant. Furthermore, suppression of
      LeIRT1 expression by NO synthesis inhibition with either tungstate or L-NAME,
      also substantially inhibited Cd uptake in roots, and the difference between N
      form treatments was diminished. Considering all of these findings, it was
      concluded that the up-regulation of the Fe uptake system was responsible for NO3-
      facilitated Cd accumulation in plants.

PMID- 22378951
TI  - Functional analysis of the relative growth rate, chemical composition,
      construction and maintenance costs, and the payback time of Coffea arabica L.
      leaves in response to light and water availability.
AB  - In this study, the combined effects of light and water availability on the
      functional relationships of the relative growth rate (RGR), leaf chemical
      composition, construction and maintenance costs, and benefits in terms of payback
      time for Coffea arabica are presented. Coffee plants were grown for 8 months in
      100% or 15% full sunlight and then a four-month water shortage was implemented.
      Plants grown under full sunlight were also transferred to shade and vice versa.
      Overall, most of the traits assessed were much more responsive to the
      availability of light than to the water supply. Larger construction costs (12%),
      primarily associated with elevated phenol and alkaloid pools, were found under
      full sunlight. There was a positive correlation between these compounds and the
      RGR, the mass-based net carbon assimilation rate and the carbon isotope
      composition ratio, which, in turn, correlated negatively with the specific leaf
      area. The payback time was remarkably lower in the sun than in shade leaves and
      increased greatly in water-deprived plants. The differences in maintenance costs
      among the treatments were narrow, with no significant impact on the RGR, and
      there was no apparent trade-off in resource allocation between growth and
      defence. The current irradiance during leaf bud formation affected both the
      specific leaf area and leaf physiology upon transferring the plants from low to
      high light and vice versa. In summary, sun-grown plants fixed more carbon for
      growth and secondary metabolism, with the net effect of an increased RGR.

PMID- 22378952
TI  - Expression of hypoallergenic Der f 2 derivatives with altered intramolecular
      disulphide bonds induces the formation of novel ER-derived protein bodies in
      transgenic rice seeds.
AB  - House dust mites (HDM) are the most common source of indoor allergens and are
      associated with allergic diseases worldwide. To benefit allergic patients, safer
      and non-invasive mucosal routes of oral administration are considered to be the
      best alternative to conventional allergen-specific immunotherapy. In this study,
      transgenic rice was developed expressing derivatives of the major HDM allergen
      Der f 2 with reduced Der f 2-specific IgE reactivity by disrupting intramolecular
      disulphide bonds in Der f 2. These derivatives were produced specifically as
      secretory proteins in the endosperm tissue of seeds under the control of the
      endosperm-specific glutelin GluB-1 promoter. Notably, modified Der f 2
      derivatives aggregated in the endoplasmic reticulum (ER) lumen and were deposited
      in a unique protein body (PB)-like structure tentatively called the Der f 2 body.
      Der f 2 bodies were characterized by their intracellular localization and physico
      chemical properties, and were distinct from ER-derived PBs (PB-Is) and protein
      storage vacuoles (PB-IIs). Unlike ER-derived organelles such as PB-Is, Der f 2
      bodies were rapidly digested in simulated gastric fluid in a manner similar to
      that of PB-IIs. Oral administration in mice of transgenic rice seeds containing
      Der f 2 derivatives encapsulated in Der f 2 bodies suppressed Der f 2-specific
      IgE and IgG production compared with that in mice fed non-transgenic rice seeds,
      and the effect was dependent on the type of Der f 2 derivative expressed. These
      results suggest that engineered hypoallergenic Der f 2 derivatives expressed in
      the rice seed endosperm could serve as a basis for the development of viable
      strategies for the oral delivery of vaccines against HDM allergy.

PMID- 22378953
TI  - Duration and extension of anatomical changes in wood structure after cambial
      injury.
AB  - Cambial injury has been reported to alter wood structure in broad-leaved trees.
      However, the duration and extension of associated anatomical changes have rarely
      been analysed thoroughly. A total of 18 young European ash (Fraxinus excelsior
      L.) trees injured on the stem by a spring flood were sampled with the aim of
      comparing earlywood vessels and rays formed prior to and after the scarring
      event. Anatomical and hydraulic parameters were measured in five successive rings
      over one-quarter of the stem circumference. The results demonstrate that
      mechanical damage induces a decrease in vessel lumen size (up to 77%) and an
      increase in vessel number (up to 475%) and ray number (up to 115%). The presence
      of more earlywood vessels and rays was observed over at least three years after
      stem scarring. By contrast, abnormally narrow earlywood vessels mainly developed
      in the first ring formed after the event, increasing the thickness-to-span ratio
      of vessels by 94% and reducing both xylem relative conductivity and the index for
      xylem vulnerability to cavitation by 54% and 32%, respectively. These vessels
      accumulated in radial groups in a 30 degrees  sector immediately adjacent to the
      wound, raising the vessel grouping index by 28%. The wound-induced anatomical
      changes in wood structure express the functional need of trees to improve xylem
      hydraulic safety and mechanical strength at the expense of water transport. Xylem
      hydraulic efficiency was restored in one year, while xylem mechanical
      reinforcement and resistance to cavitation and decay lasted over several years.

PMID- 22378954
TI  - Mechanisms for cellular transport and release of allelochemicals from plant roots
      into the rhizosphere.
AB  - Allelochemicals and other metabolites released by plant roots play important
      roles in rhizosphere signalling, plant defence and responses to abiotic stresses.
      Plants use a variety of sequestration and transport mechanisms to move and export
      bioactive products safely into the rhizosphere. The use of mutants and molecular
      tools to study gene expression has revealed new information regarding the diverse
      group of transport proteins and conjugation processes employed by higher plants.
      Transport systems used for moving secondary products into and out of root cells
      are similar to those used elsewhere in the plant but are closely linked to soil
      environmental conditions and local root health. Root cells can rapidly generate
      and release large quantities of allelochemicals in response to stress or local
      rhizosphere conditions, so the production and transport of these compounds in
      cells are often closely linked. Plants need to manage the potentially toxic
      allelochemicals and metabolites they produce by sequestering them to the vacuole
      or other membrane-bound vesicles. These compartments provide secure storage areas
      and systems for safely moving bioactive chemicals throughout the cytosol. Release
      into the apoplast occurs either by exocytosis or through membrane-bound transport
      proteins. This review discusses the possible transport mechanisms involved in
      releasing specific root-produced allelochemicals by combining microscopic
      observations of the specialized root cells with the physical and chemical
      properties of the exudates.

PMID- 22378955
TI  - Misuse of statistics continues to plague healthcare, conference hears.

PMID- 22378956
TI  - UK government agrees to fund free drug treatment for foreign nationals with HIV.

PMID- 22378957
TI  - Vital sign abnormalities, rapid response, and adverse outcomes in hospitalized
      patients.
AB  - Rapid response activation (RRA), triggered chiefly by surpassing threshold vital
      sign abnormalities (TVSAs), is designed to intervene at the earliest point in a
      patient's deteriorating course. The authors aimed to quantify the incidence of
      TVSA among patients hospitalized on acute care units in a hospital that uses
      rapid response. During the course of 6 months, the authors compared adverse
      events (mortality, unexpected intensive care unit [ICU] transfers, and
      cardiopulmonary arrest) and TVSA among patients who triggered an RRA, patients
      with TVSAs and no RRA, and all other patients. At least 1 TVSA was recorded in
      31.9% of stays and 12.2% of patient-days. RRA patients were more likely (22.5%)
      than other TVSA patients (7.9%) and other patients (1.8%) to have an adverse
      event (P < .01). Incidence varied by vital sign. During the investigation, only
      2.5% of TVSA opportunities triggered an RRA. As systems engage electronic
      workflows, automatically triggering RRAs based solely on TVSAs could place a
      tremendous burden on systems.

PMID- 22378958
TI  - Improving prompt effectiveness in diabetes care: an intervention study.
AB  - Electronic medical records (EMRs) should support clinical decision making to
      further quality care delivery. This study describes 1 academic medical group's
      efforts to leverage their EMR's decision-support functionality to improve quality
      care delivery. A nested, time-series, quasiexperimental design compared 3
      different implementation strategies for EMR prompting at 5 primary care clinics
      in a single academic medical group. The primary outcome was the ordering of all
      indicated diabetes monitoring tests before the end of the visit. The authors
      analyzed 16 511 visits performed on 3730 patients. The rate of ordering all
      indicated tests at the time of the visit increased from 29% with no prompts to
      49% (P < .001) with appropriately designed prompts and training support. EMR
      generated prompts may be more likely to increase ordering of recommended
      monitoring tests when clinic workflow, staff training, and medical culture are
      incorporated into the prompt delivery.

PMID- 22378960
TI  - The origin of spelt and free-threshing hexaploid wheat.
AB  - It is widely believed that hexaploid wheat originated via hybridization of hulled
      tetraploid emmer with Aegilops tauschii (genomes DD) and that the nascent
      hexaploid was spelt, from which free-threshing wheat evolved by mutations. To
      reassess the role of spelt in the evolution of Triticum aestivum, 4 disomic
      substitution lines of Ae. tauschii chromosome 2D in Chinese Spring wheat were
      developed and one of them was used to map the Tg locus, which controls glume
      tenacity in Ae. tauschii, relative to simple sequence repeat (SSR) and expressed
      sequence tag loci on wheat chromosome 2D. The segregation of SSR markers was used
      to assess the presence of Tg alleles in 11 accessions of spelt, both from Europe
      and from Asia. Ten of them had an inactive tg allele in the D genome and most had
      an active Tg allele in the B genome. This is consistent with spelt being derived
      from free-threshing hexaploid wheat by hybridization of free-threshing wheat with
      hulled emmer. It is proposed that the tetraploid parent of hexaploid wheat was
      not hulled emmer but a free-threshing form of tetraploid wheat.

PMID- 22378959
TI  - Haldane's rule in marsupials: what happens when both sexes are functionally
      hemizygous?
AB  - During the process of speciation, diverging taxa often hybridize and produce
      offspring wherein the heterogametic sex (i.e., XY or ZW) is unfit (Haldane's
      rule). Dominance theory seeks to explain Haldane's rule in terms of the
      difference in X-linked dominance regimes experienced by the sexes. However, X
      inactivation in female mammals extends the effects of hemizygosity to both sexes.
      Here, we highlight where the assumptions of dominance theory are particularly
      problematic in marsupials, where X inactivation uniformly results in silencing
      the paternal X. We then present evidence of Haldane's rule for sterility but not
      for viability in marsupials, as well as the first violations of Haldane's rule
      for these traits among all mammals. Marsupials represent a large taxonomic group
      possessing heteromorphic sex chromosomes, where the dominance theory cannot
      explain Haldane's rule. In this light, we evaluate alternative explanations for
      the preponderance of male sterility in interspecific hybrids, including faster
      male evolution, X-Y interactions, and genomic conflict hypotheses.

PMID- 20029605
TI  - The Contribution of the PB1-F2 Protein to the Fitness of Influenza A Viruses and
      its Recent Evolution in the 2009 Influenza A (H1N1) Pandemic Virus.
AB  - The absence of a full-length PB1-F2 protein has been suggested as one possible
      determinant for the low pathogenicity of the 2009 Influenza A H1N1 pandemic
      strain. Since the PB1-F2 sequence of this strain has three stop codons and its
      ancestors encode a full-length protein, the stop codons must have appeared
      recently. This suggests that the PB1-F2 protein is not evolutionary and
      functionally important for the new virus. We investigate the role of this protein
      in the evolution of influenza A viruses, and in particular in relation to the
      history of the new strain. We show that its evolutionary history is comparable to
      other, non-translated, subsequences in the PB1 segment, suggesting that PB1-F2
      does not contribute significantly to the fitness of the influenza A virus.

PMID- 20029605
TI  - The Contribution of the PB1-F2 Protein to the Fitness of Influenza A Viruses and
      its Recent Evolution in the 2009 Influenza A (H1N1) Pandemic Virus.
AB  - The absence of a full-length PB1-F2 protein has been suggested as one possible
      determinant for the low pathogenicity of the 2009 Influenza A H1N1 pandemic
      strain. Since the PB1-F2 sequence of this strain has three stop codons and its
      ancestors encode a full-length protein, the stop codons must have appeared
      recently. This suggests that the PB1-F2 protein is not evolutionary and
      functionally important for the new virus. We investigate the role of this protein
      in the evolution of influenza A viruses, and in particular in relation to the
      history of the new strain. We show that its evolutionary history is comparable to
      other, non-translated, subsequences in the PB1 segment, suggesting that PB1-F2
      does not contribute significantly to the fitness of the influenza A virus.

PMID- 20029604
TI  - Conditions Under Which Predispensing of Antiviral Drugs to Individuals at High
      Risk of Death from Pandemic Influenza Is Expected to Save Lives: Predispensing of
      Antiviral Drugs to Individuals at High Risk of Severe Outcomes of H1N1 Influenza.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      lives saved by antivirals in the whole population. Predispensing has two
      potential benefits: first, individuals to whom antivirals have been predispensed
      may be able to initiate treatment earlier than if they had to wait to obtain and
      fill a prescription, reducing their risk of progression to severe disease.
      Second, if demand exceeds supply, predispensing to high-risk individuals
      increases the chance that the course will be used by a high-risk, rather than a
      low-risk individual. The disadvantage of predispensing is that a course may be
      sequestered by a person who does not need it (because s/he does not become
      infected) or wastes it (using it for something other than influenza). We derive
      mathematical conditions under which the advantages outweigh the disadvantages and
      suggest that for individuals at considerably higher than average risk of death
      from pandemic influenza (for example, greater than approximately 5x the
      population average risk), predispensing of antivirals up to perhaps 20% of the
      total antiviral stockpile is very likely to result in a net savings of life. Data
      to parameterize this model are limited, but we believe such a policy would be
      robust to a reasonable range of uncertainty, and we note that decisions about
      predispensing will need to be made before definitive data are available. More
      precise estimates of the relative risk of death for groups beyond pregnant women
      are urgently needed for decision making about prioritization of antivirals,
      vaccines and other countermeasures.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      lives saved by antivirals in the whole population. Predispensing has two
      potential benefits: first, individuals to whom antivirals have been predispensed
      may be able to initiate treatment earlier than if they had to wait to obtain and
      fill a prescription, reducing their risk of progression to severe disease.
      Second, if demand exceeds supply, predispensing to high-risk individuals
      increases the chance that the course will be used by a high-risk, rather than a
      low-risk individual. The disadvantage of predispensing is that a course may be
      sequestered by a person who does not need it (because s/he does not become
      infected) or wastes it (using it for something other than influenza). We derive
      mathematical conditions under which the advantages outweigh the disadvantages and
      suggest that for individuals at considerably higher than average risk of death
      from pandemic influenza (for example, greater than approximately 5x the
      population average risk), predispensing of antivirals up to perhaps 20% of the
      total antiviral stockpile is very likely to result in a net savings of life. Data
      to parameterize this model are limited, but we believe such a policy would be
      robust to a reasonable range of uncertainty, and we note that decisions about
      predispensing will need to be made before definitive data are available. More
      precise estimates of the relative risk of death for groups beyond pregnant women
      are urgently needed for decision making about prioritization of antivirals,
      vaccines and other countermeasures.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      lives saved by antivirals in the whole population. Predispensing has two
      potential benefits: first, individuals to whom antivirals have been predispensed
      may be able to initiate treatment earlier than if they had to wait to obtain and
      fill a prescription, reducing their risk of progression to severe disease.
      Second, if demand exceeds supply, predispensing to high-risk individuals
      increases the chance that the course will be used by a high-risk, rather than a
      low-risk individual. The disadvantage of predispensing is that a course may be
      sequestered by a person who does not need it (because s/he does not become
      infected) or wastes it (using it for something other than influenza). We derive
      mathematical conditions under which the advantages outweigh the disadvantages and
      suggest that for individuals at considerably higher than average risk of death
      from pandemic influenza (for example, greater than approximately 5x the
      population average risk), predispensing of antivirals up to perhaps 20% of the
      total antiviral stockpile is very likely to result in a net savings of life. Data
      to parameterize this model are limited, but we believe such a policy would be
      robust to a reasonable range of uncertainty, and we note that decisions about
      predispensing will need to be made before definitive data are available. More
      precise estimates of the relative risk of death for groups beyond pregnant women
      are urgently needed for decision making about prioritization of antivirals,
      vaccines and other countermeasures.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      lives saved by antivirals in the whole population. Predispensing has two
      potential benefits: first, individuals to whom antivirals have been predispensed
      may be able to initiate treatment earlier than if they had to wait to obtain and
      fill a prescription, reducing their risk of progression to severe disease.
      Second, if demand exceeds supply, predispensing to high-risk individuals
      increases the chance that the course will be used by a high-risk, rather than a
      low-risk individual. The disadvantage of predispensing is that a course may be
      sequestered by a person who does not need it (because s/he does not become
      infected) or wastes it (using it for something other than influenza). We derive
      mathematical conditions under which the advantages outweigh the disadvantages and
      suggest that for individuals at considerably higher than average risk of death
      from pandemic influenza (for example, greater than approximately 5x the
      population average risk), predispensing of antivirals up to perhaps 20% of the
      total antiviral stockpile is very likely to result in a net savings of life. Data
      to parameterize this model are limited, but we believe such a policy would be
      robust to a reasonable range of uncertainty, and we note that decisions about
      predispensing will need to be made before definitive data are available. More
      precise estimates of the relative risk of death for groups beyond pregnant women
      are urgently needed for decision making about prioritization of antivirals,
      vaccines and other countermeasures.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      severe outcomes (such as deaths or hospitalizations) prevented by antivirals in
      the whole population. One potential benefit of predispensing is that individuals
      to whom antivirals have been predispensed may be able to initiate treatment
      earlier than if they had to wait to obtain and fill a prescription, reducing
      their risk of progression to severe disease. If this benefit exceeds the side
      effects of misuse for the category of individuals to whom antivirals were
      predispensed, and if antiviral supply exceeds overall population demand (which
      appears relevant for several countries including US in the current H1N1
      pandemic), predispensing a quantity of antivirals not exceeding the difference
      between supply and demand is always beneficial. In this paper we consider the net
      benefits of predispensing antivirals under various scenarios, including demand
      exceeding supply, and derive mathematical conditions under which antiviral
      predispensing is advantageous on balance. For individuals whose relative risk of
      severe outcome is high enough, such as immunosuppressed individuals (particularly
      children) and possibly individuals with neurological disorders, predispensing is
      always beneficial at a given level of antiviral stockpile with modest assumptions
      on the relative benefit of early treatment by a predispensed course, regardless
      of the overall population demand for antivirals during the course of an epidemic.
      Making additional assumptions on either the overall population demand for
      antivirals (which appear relevant in the current situation) or on the relative
      benefit of predispensing would make predispensing net beneficial with inclusion
      of a larger number of persons such as pregnant women and morbidly obese adults.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      severe outcomes (such as deaths or hospitalizations) prevented by antivirals in
      the whole population. One potential benefit of predispensing is that individuals
      to whom antivirals have been predispensed may be able to initiate treatment
      earlier than if they had to wait to obtain and fill a prescription, reducing
      their risk of progression to severe disease. If this benefit exceeds the side
      effects of misuse for the category of individuals to whom antivirals were
      predispensed, and if antiviral supply exceeds overall population demand (which
      appears relevant for several countries including US in the current H1N1
      pandemic), predispensing a quantity of antivirals not exceeding the difference
      between supply and demand is always beneficial. In this paper we consider the net
      benefits of predispensing antivirals under various scenarios, including demand
      exceeding supply, and derive mathematical conditions under which antiviral
      predispensing is advantageous on balance. For individuals whose relative risk of
      severe outcome is high enough, such as immunosuppressed individuals (particularly
      children) and possibly individuals with neurological disorders, predispensing is
      always beneficial at a given level of antiviral stockpile with modest assumptions
      on the relative benefit of early treatment by a predispensed course, regardless
      of the overall population demand for antivirals during the course of an epidemic.
      Making additional assumptions on either the overall population demand for
      antivirals (which appear relevant in the current situation) or on the relative
      benefit of predispensing would make predispensing net beneficial with inclusion
      of a larger number of persons such as pregnant women and morbidly obese adults.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      severe outcomes (such as deaths or hospitalizations) prevented by antivirals in
      the whole population. One potential benefit of predispensing is that individuals
      to whom antivirals have been predispensed may be able to initiate treatment
      earlier than if they had to wait to obtain and fill a prescription, reducing
      their risk of progression to severe disease. If this benefit exceeds the side
      effects of misuse for the category of individuals to whom antivirals were
      predispensed, and if antiviral supply exceeds overall population demand (which
      appears relevant for several countries including US in the current H1N1
      pandemic), predispensing a quantity of antivirals not exceeding the difference
      between supply and demand is always beneficial. In this paper we consider the net
      benefits of predispensing antivirals under various scenarios, including demand
      exceeding supply, and derive mathematical conditions under which antiviral
      predispensing is advantageous on balance. For individuals whose relative risk of
      severe outcome is high enough, such as immunosuppressed individuals (particularly
      children) and possibly individuals with neurological disorders, predispensing is
      always beneficial at a given level of antiviral stockpile with modest assumptions
      on the relative benefit of early treatment by a predispensed course, regardless
      of the overall population demand for antivirals during the course of an epidemic.
      Making additional assumptions on either the overall population demand for
      antivirals (which appear relevant in the current situation) or on the relative
      benefit of predispensing would make predispensing net beneficial with inclusion
      of a larger number of persons such as pregnant women and morbidly obese adults.

PMID- 20029610
TI  - Reassortment patterns in Swine influenza viruses.
AB  - Previous human influenza pandemics were the results of emerging viruses from non
      human reservoirs, with at least two caused by strains of mixed human and avian
      origin. Also, many cases of swine influenza viruses have reportedly infected
      humans, including the recent human H1N1 strain, isolated in Mexico and the United
      States. Pigs are documented to get infected with human, avian, and swine viruses
      and allow productive replication, thus it has been conjectured that they are the
      "mixing vessel" that create reassortant strains, causing the human pandemics. In
      this paper, we apply several statistical techniques to an ensemble of publicly
      available swine viruses to study the reassortment phenomena. The reassortment
      patterns in swine viruses confirm previous results found in human viruses that
      the glycoprotein coding segments reassort most often. Moreover, one of the
      polymerase segments (PB1), reassorted in the strains responsible for the last two
      human pandemics of 1957 and 1968, also reassorts frequently.

PMID- 20029606
TI  - Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection:
      Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal
      influenza.
AB  - On June 11, 2009 the World Health Organization (WHO) declared a new H1N1
      influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and
      H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new
      virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2
      human strains. Using the ferret model, we investigated which of these three
      possibilities were most likely favored. Our studies showed that the current
      pandemic virus is more transmissible than, and has a biological advantage over,
      prototypical seasonal H1 or H3 strains.

PMID- 20029607
TI  - Mortality and morbidity burden associated with A/H1N1pdm influenza virus: Who is
      likely to be infected, experience clinical symptoms, or die from the H1N1pdm 2009
      pandemic virus ?
AB  - Here we use lessons from past influenza pandemics and recent information about
      the H1N1pdm pandemic to discuss variations in H1N1pdm disease burden with age,
      underlying risk factors, and geography.

PMID- 20029608
TI  - Tracking the evolution and geographic spread of Influenza A.
AB  - The 2009 swine-origin strain of Influenza A H1N1 has spread to nearly all parts
      of the world, with 175 countries reporting confirmed cases thus far. Consistent
      with seasonal flu outbreaks, the current pandemic strain has shown rapid
      dispersal, with multiple examples of introduction into different geographic
      regions. Here we use an automated pipeline to collect data for analysis in the
      geospatial package GenGIS, which allows the geographic and temporal tracking of
      new sequence types and polymorphisms. Using this approach, we examine a pair of
      amino acid changes in the neuraminidase protein that are implicated in antibody
      recognition, and exhibit global dispersal with little or no geographic structure.

PMID- 20029609
TI  - Molecular modeling of swine influenza A/H1N1, Spanish H1N1, and avian H5N1 flu N1
      neuraminidases bound to Tamiflu and Relenza.
AB  - A molecular model of the swine influenza A/H1N1 type-I neuraminidase was built
      using the pathogenic avian H5N1 type-I neuraminidase as a basis, due to the
      higher sequence identity between A/H1N1 and H5N1 (91.47%) compared to Spanish
      H1N1 (88.37%) neuraminidase. All-atom molecular dynamics (MD) simulations of all
      three neuraminidases were performed, either as apo-structures or with commercial
      antiviral drugs Tamiflu or Relenza separately bound; the simulations allowed for
      the identification of both conserved and unique drug-protein interactions across
      all three proteins. Specifically, conserved networks of hydrogen bonds
      stabilizing the drugs in the sialic acid binding site of the simulated
      neuraminidases are analyzed, providing insight into how disruption due to
      mutations may lead to increased drug resistance. In addition, a possible
      mechanism through which the residue 294 mutation acquires drug resistance is
      proposed by mapping the mutation site onto an electrostatic pathway which may
      play a role in controlling drug access to the binding pocket of neuraminidase,
      establishing a starting point for further investigations of neuraminidase drug
      resistance.

PMID- 20029609
TI  - Molecular modeling of swine influenza A/H1N1, Spanish H1N1, and avian H5N1 flu N1
      neuraminidases bound to Tamiflu and Relenza.
AB  - A molecular model of the swine influenza A/H1N1 type-I neuraminidase was built
      using the pathogenic avian H5N1 type-I neuraminidase as a basis, due to the
      higher sequence identity between A/H1N1 and H5N1 (91.47%) compared to Spanish
      H1N1 (88.37%) neuraminidase. All-atom molecular dynamics (MD) simulations of all
      three neuraminidases were performed, either as apo-structures or with commercial
      antiviral drugs Tamiflu or Relenza separately bound; the simulations allowed for
      the identification of both conserved and unique drug-protein interactions across
      all three proteins. Specifically, conserved networks of hydrogen bonds
      stabilizing the drugs in the sialic acid binding site of the simulated
      neuraminidases are analyzed, providing insight into how disruption due to
      mutations may lead to increased drug resistance. In addition, a possible
      mechanism through which the residue 294 mutation acquires drug resistance is
      proposed by mapping the mutation site onto an electrostatic pathway which may
      play a role in controlling drug access to the binding pocket of neuraminidase,
      establishing a starting point for further investigations of neuraminidase drug
      resistance.

PMID- 20029609
TI  - Molecular modeling of swine influenza A/H1N1, Spanish H1N1, and avian H5N1 flu N1
      neuraminidases bound to Tamiflu and Relenza.
AB  - A molecular model of the swine influenza A/H1N1 ( also called H1N1pdm) type-I
      neuraminidase was built using the pathogenic avian H5N1 type-I neuraminidase as a
      basis, due to the higher sequence identity between A/H1N1 and H5N1 (91.47%)
      compared to Spanish H1N1 (88.37%) neuraminidase. All-atom molecular dynamics (MD)
      simulations of all three neuraminidases were performed, either as apo-structures
      or with commercial antiviral drugs Tamiflu or Relenza separately bound; the
      simulations allowed for the identification of both conserved and unique drug
      protein interactions across all three proteins. Specifically, conserved networks
      of hydrogen bonds stabilizing the drugs in the sialic acid binding site of the
      simulated neuraminidases are analyzed, providing insight into how disruption due
      to mutations may lead to increased drug resistance. In addition, a possible
      mechanism through which the residue 294 mutation acquires drug resistance is
      proposed by mapping the mutation site onto an electrostatic pathway which may
      play a role in controlling drug access to the binding pocket of neuraminidase,
      establishing a starting point for further investigations of neuraminidase drug
      resistance.

PMID- 20029612
TI  - Top-hits for A/H1N1 Identified by Virtual Screening Using Ensemble-based Docking.
AB  - A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm
      strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of
      the bird flu H5N1, an effective means to quickly identify top candidates for use
      against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI
      diversity set which bind best to H5N1 neuraminidase. These compounds serve as
      viable candidates for docking against the H1N1pdm neuraminidase, using ensembles
      extracted from molecular dynamics simulations of the H1N1pdm system. The ranking
      order of these top candidates was found to be different from the previously
      published results for H5N1. The results indicated that the Oseltamivir (Tamiflu)
      and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six
      drug candidates were found to bind more effectively to H1N1pdm neuraminidase than
      Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also
      provided.

PMID- 20029612
TI  - Top-hits for A/H1N1 Identified by Virtual Screening Using Ensemble-based Docking.
AB  - A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm
      strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of
      the bird flu H5N1, an effective means to quickly identify top candidates for use
      against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI
      diversity set which bind best to H5N1 neuraminidase. These compounds serve as
      viable candidates for docking against the H1N1pdm neuraminidase, using ensembles
      extracted from molecular dynamics simulations of the H1N1pdm system. The ranking
      order of these top candidates was found to be different from the previously
      published results for H5N1. The results indicated that the Oseltamivir (Tamiflu)
      and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six
      drug candidates were found to bind more effectively to H1N1pdm neuraminidase than
      Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also
      provided.

PMID- 20029613
TI  - Reconstructing the initial global spread of a human influenza pandemic: A
      Bayesian spatial-temporal model for the global spread of H1N1pdm.
AB  - Here, we present an analysis of the H1N1pdm genetic data sampled over the initial
      stages in the epidemic. To infer phylodynamic spread in time and space we employ
      a recently developed Bayesian statistical inference framework (Lemey et al., in
      press). We model spatial diffusion as a continuous-time Markov chain process
      along time-measured genealogies. In this analysis, we consider 40 locations for
      which sequence data were available on 06-Aug-2009. The sampling time interval of
      the 242 sequences spans from 30-Mar-2009 to 12-Jul-2009. The Bayesian inference
      typically results in a posterior distribution of phylogenetic trees, each having
      an estimate of the epidemic locations at the ancestral nodes in the tree. We
      summarize these trees using the most representative clustering pattern and
      annotate these clusters with the most probable location states. We can visualize
      this information as tree that grows over time, seeding locations each time an
      ancestral node is inferred to exist at a different location. A Bayes factor test
      provides statistical support for epidemiological linkage throughout the
      evolutionary history. We demonstrate how our full probabilistic approach
      efficiently tracks an epidemic based on viral genetic data as it unfolds across
      the globe.

PMID- 20029615
TI  - E14-F55 combination in M2 protein: a putative molecular determinant responsible
      for swine-origin influenza A virus transmission in humans.
AB  - The species-specific signatures of the swine-origin influenza A (H1N1) virus (S
      OIV), which caused the current influenza pandemic, have not been well defined. By
      comparing the protein sequences of S-OIVs with those of swine, avian and human
      influenza viruses, we found that that almost all human IAVs and those causing
      influenza pandemics, including the 2009 S-OIVs, had a combination of glutamic
      acid (E) residue at position 14 and phenylalanine (F) residue at position 55 in
      their M2 protein, while only 22% and 4% of the swine and avian IAVs had the E14
      F55 combination. These finding suggests that E14-F55 combination in the M2
      protein of S-OIV may be a molecular determinant associated with its human-to
      human transmission.

PMID- 20029616
TI  - The shifting demographic landscape of influenza.
AB  - BACKGROUND: As Pandemic (H1N1) 2009 influenza spreads around the globe, it
      strikes school-age children more often than adults. Although there is some
      evidence of pre-existing immunity among older adults, this alone may not explain
      the significant gap in age-specific infection rates. METHODS & FINDINGS: Based on
      a retrospective analysis of pandemic strains of influenza from the last century,
      we show that school-age children typically experience the highest attack rates in
      primarily naive populations, with the burden shifting to adults during the
      subsequent season. Using a parsimonious network-based mathematical model which
      incorporates the changing distribution of contacts in the susceptible population,
      we demonstrate that new pandemic strains of influenza are expected to shift the
      epidemiological landscape in exactly this way. CONCLUSIONS: Our results provide a
      simple demographic explanation for the age bias observed for H1N1/09 attack
      rates, and a prediction that this bias will shift in coming months. These results
      also have significant implications for the allocation of public health resources
      including vaccine distribution policies.

PMID- 20029660
TI  - Antiviral usage for H1N1 treatment: pros, cons and an argument for broader
      prescribing guidelines in the United States.
AB  - Current CDC guidelines for antiviral treatment of people with influenza like
      illness (ILI) effectively discourage treatment of people with no underlying
      medical conditions unless they exhibit severe symptoms, such as evidence of lower
      respiratory tract infection or clinical deterioration. This guidance is unlike
      that provided by some other countries, which allow for treatment of most
      moderately symptomatic individuals. We examine evidence for benefits of antiviral
      usage for influenza treatment, including its relation to severe outcomes for the
      current pandemic H1N1 strain. We also discuss some of the potential cons of
      antiviral usage. In the current situation in the US, with an elevated and
      evidently growing burden of influenza hospitalizations and mortality, a high
      percentage of individuals infected with influenza (with almost all of those
      carrying the H1N1pdm strain) among those who exhibit ILI and get tested for
      influenza virus, very low levels of antiviral resistance and little time left for
      antiviral resistance to take off before large quantities of vaccine become
      available, we think it is worthwhile to consider a revision to the current
      antiviral usage recommendations, such that physicians would be encouraged to
      consider prescribing antivirals to individuals with moderate to severe symptoms
      who present for treatment.Note: Very recently CDC has adopted clarifications for
      its antiviral usage guidelines:
      http://www.cdc.gov/H1N1flu/antivirals/facts_clinicians.htm.

PMID- 20029662
TI  - Mining the NCBI Influenza Sequence Database: adaptive grouping of BLAST results
      using precalculated neighbor indexing.
AB  - The Influenza Virus Resource and other Virus Variation Resources at NCBI provide
      enhanced visualization web tools for exploratory analysis for influenza sequence
      data. Despite the improvements in data analysis, the initial data retrieval
      remains unsophisticated, frequently producing huge and imbalanced datasets due to
      the large number of identical and nearly-identical sequences in the database.We
      propose a data mining algorithm to organize reported sequences into groups based
      on their relatedness to the query sequence and to each other. The algorithm uses
      BLAST to find database sequences related to the query. Neighbor lists
      precalculated from pairwise BLAST alignments between database sequences are used
      to organize results in groups of nearly-identical and strongly related sequences.
      We propose to use a non-symmetric dissimilarity measure well crafted for dealing
      with sequences of different length (fragments).A balanced and representative data
      set produced by this tool can be used for further analysis, i.e. multiple
      sequence alignment and phylogenetic trees. The algorithm is implemented for
      protein coding sequences and is being integrated with the NCBI Influenza Virus
      Resource.

PMID- 20029663
TI  - Quantifying the transmissibility of human influenza and its seasonal variation in
      temperate regions.
AB  - Seasonal influenza has considerable impact around the world, both economically
      and in mortality among risk groups. The long term patterns of disease are hard to
      capture with simple models, while the interplay of epidemiological processes with
      antigenic evolution makes detailed modelling difficult and computationally
      intensive. We identify a number of characteristic features of flu incidence time
      series in temperate regions, including ranges of annual attack rates and outbreak
      durations. We construct pseudo-likelihoods to capture these characteristic
      features and examine the ability of a collection of simple models to reproduce
      them under seasonal variation in transmission. Results indicate that an age
      structured model with non-random mixing and co-circulating strains are both
      required to match time series data. The extent of matching behaviour also serves
      to define informative ranges for parameters governing essential dynamics. Our
      work gives estimates of the seasonal peak basic reproduction, R0, in the range
      1.7-2.1, with the degree of seasonal variation having limited impact of these
      estimates. We find that it is only really possible to estimate a lower bound on
      the degree of seasonal variation in influenza transmissibility, namely that
      transmissibility in the low transmission season may be only 5-10% less than the
      peak value. These results give some insight into the extent to which
      transmissibility of the H1N1pdm pandemic virus may increase in Northern
      Hemisphere temperate countries in winter 2009. We find that the timescale for
      waning of immunity to current circulating seasonal influenza strain is between 4
      and 8 years, consistent with studies of the antigenic variation of influenza, and
      that inter-subtype cross-immunity is restricted to low levels.

PMID- 20029663
TI  - Quantifying the transmissibility of human influenza and its seasonal variation in
      temperate regions.
AB  - Seasonal influenza has considerable impact around the world, both economically
      and in mortality among risk groups. The long term patterns of disease are hard to
      capture with simple models, while the interplay of epidemiological processes with
      antigenic evolution makes detailed modelling difficult and computationally
      intensive. We identify a number of characteristic features of flu incidence time
      series in temperate regions, including ranges of annual attack rates and outbreak
      durations. We construct pseudo-likelihoods to capture these characteristic
      features and examine the ability of a collection of simple models to reproduce
      them under seasonal variation in transmission. Results indicate that an age
      structured model with non-random mixing and co-circulating strains are both
      required to match time series data. The extent of matching behaviour also serves
      to define informative ranges for parameters governing essential dynamics. Our
      work gives estimates of the seasonal peak basic reproduction, R0, in the range
      1.7-2.1, with the degree of seasonal variation having limited impact of these
      estimates. We find that it is only really possible to estimate a lower bound on
      the degree of seasonal variation in influenza transmissibility, namely that
      transmissibility in the low transmission season may be only 5-10% less than the
      peak value. These results give some insight into the extent to which
      transmissibility of the H1N1pdm pandemic virus may increase in Northern
      Hemisphere temperate countries in winter 2009. We find that the timescale for
      waning of immunity to current circulating seasonal influenza strain is between 4
      and 8 years, consistent with studies of the antigenic variation of influenza, and
      that inter-subtype cross-immunity is restricted to low levels.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029663
TI  - Quantifying the transmissibility of human influenza and its seasonal variation in
      temperate regions.
AB  - Seasonal influenza has considerable impact around the world, both economically
      and in mortality among risk groups. The long term patterns of disease are hard to
      capture with simple models, while the interplay of epidemiological processes with
      antigenic evolution makes detailed modelling difficult and computationally
      intensive. We identify a number of characteristic features of flu incidence time
      series in temperate regions, including ranges of annual attack rates and outbreak
      durations. We construct pseudo-likelihoods to capture these characteristic
      features and examine the ability of a collection of simple models to reproduce
      them under seasonal variation in transmission. Results indicate that an age
      structured model with non-random mixing and co-circulating strains are both
      required to match time series data. The extent of matching behaviour also serves
      to define informative ranges for parameters governing essential dynamics. Our
      work gives estimates of the seasonal peak basic reproduction, R0, in the range
      1.7-2.1, with the degree of seasonal variation having limited impact of these
      estimates. We find that it is only really possible to estimate a lower bound on
      the degree of seasonal variation in influenza transmissibility, namely that
      transmissibility in the low transmission season may be only 5-10% less than the
      peak value. These results give some insight into the extent to which
      transmissibility of the H1N1pdm pandemic virus may increase in Northern
      Hemisphere temperate countries in winter 2009. We find that the timescale for
      waning of immunity to current circulating seasonal influenza strain is between 4
      and 8 years, consistent with studies of the antigenic variation of influenza, and
      that inter-subtype cross-immunity is restricted to low levels.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029668
TI  - The Early Transmission Dynamics of H1N1pdm Influenza in the United Kingdom.

PMID- 20029669
TI  - H1N1 vaccination and adults with underlying health conditions in the US.
AB  - 65% of fatalities from pH1N1 infections in a large US case series occur in adults
      with underlying health conditions other than pregnancy, but it appears that only
      relatively few high-risk adults will get vaccinated during the fall wave of pH1N1
      transmission. There are several reasons for this problem; the most important is
      vaccine shortage. High risk adults (other than pregnant women) were not part of
      the initial, narrow priority cohort which included pregnant women and children
      ages 0.5-4; this is despite the fact that some of those high risk groups, such as
      adults with immunosuppressive conditions and possibly individuals with
      neurological disorders, have a relative risk for fatality (per capita) higher
      than pregnant women, and over 28-fold higher than healthy children under the age
      of 4. With more vaccine becoming available than needed in the initial priority
      cohort, a broader group which includes high risk adults and individuals under 24
      becomes eligible for vaccine in many locations. Nonetheless, due to continuing
      high demand, high-risk adults face competition for vaccine from healthy
      individuals under 24; additionally, some locations specifically prioritize school
      students over high-risk adults. Finally, there is an issue of awareness and a
      shortage of specific channels that target high risk adults other than pregnant
      women and facilitate vaccine distribution among them in the US.

PMID- 20033093
TI  - Optimizing allocation for a delayed influenza vaccination campaign.
AB  - During unexpected infectious disease outbreaks, public health agencies must make
      effective use of limited resources. Vaccine distribution may be delayed and
      staggered through time, as underscored by the 2009 H1N1 influenza pandemic. Using
      a mathematical model parametrized with data from the 2009 H1N1 pandemic, we found
      that optimal allocations of vaccine among people in different age groups and
      people with high-risk conditions depends on the schedule of vaccine availability
      relative to the progress of the epidemic. For the projected schedule of H1N1
      vaccine availability, the optimal strategy to reduce influenza-related deaths is
      to initial target high-risk people, followed by school-aged children (5-17) and
      then young adults (18-44). The optimal strategy to minimize hospitalizations,
      however, is to target ages 5-44 throughout the vaccination campaign, with only a
      tiny amount of vaccine used on high-risk people. We find that optimizing at each
      vaccine release time independently does not give the overall optimal strategy. In
      this manuscript, we derive policy recommendations for 2009 H1N1 vaccine
      allocation using a mathematical model. In addition, our optimization procedures,
      which consider staggered releases over the entire epidemic altogether, are
      applicable to other outbreaks where not all supplies are available initially.

PMID- 20023711
TI  - Studies needed to address public health challenges of the 2009 H1N1 influenza
      pandemic: insights from modeling.
AB  - The 2009 influenza pandemic (H1N1pdm) has completed its first wave in many
      northern and southern hemisphere populations and many northern hemisphere
      populations are reporting substantial activity indicating the start of a second
      wave this autumn. As the global epidemiology of this novel strain unfolds,
      substantial policy challenges will continue to present themselves for the next 12
      to 18 months. Here, we anticipate six public health challenges and identify data
      that are required for public health decision making. In particular, we suggest
      studies that will generate data not otherwise available from routine
      surveillance. Representative serological surveys stand out as a critical source
      of data with which to reduce uncertainty around policy choices for both
      pharmaceutical and non-pharmaceutical interventions after the initial wave has
      passed. Also, monitoring the time course of incidence of severe H1N1pdm cases
      will give a clear picture of variability in underlying transmissibility of the
      virus during population wide changes in behavior such as school vacations and
      other non-pharmaceutical interventions. In addition, we address low resource
      settings where routine surveillance for influenza has not been established and
      suggest alternative ways to collect data for the 2009 (and beyond) influenza H1N1
      pandemic.

PMID- 20043033
TI  - Epidemiological characteristics and low case fatality rate of pandemic (H1N1)
      2009 in Japan.
AB  - Pandemic (H1N1) 2009 has been causing large outbreaks in Japan. Yet, the case
      fatality rate (CFR) remains low and only 85 deaths have been confirmed as of
      December 17, 2009. Surveillance data was analyzed to define epidemiological
      characteristics of pandemic (H1N1) 2009 in Japan. It was shown that most of the
      reported influenza-like illness cases and hospitalizations have occurred in those
      aged 5-9 years and 10-14 years, in whom CFR is extremely low. However, CFRs are
      higher in small children (<5 years) and adults. The transmission to these age
      groups may possibly have been minimized through aggressive suspension of classes
      in schools.

PMID- 20066155
TI  - Absolute Humidity and the Seasonal Onset of Influenza in the Continental US.
AB  - Much of the observed wintertime increase of mortality in temperate regions is
      attributed to seasonal influenza. A recent re-analysis of laboratory experiments
      indicates that absolute humidity strongly modulates the airborne survival and
      transmission of the influenza virus. Here we extend these findings to the human
      population level, showing that the onset of increased wintertime influenza
      related mortality in the United States is associated with anomalously low
      absolute humidity levels during the prior weeks. We then use an epidemiological
      model, in which observed absolute humidity conditions temper influenza
      transmission rates, to successfully simulate the seasonal cycle of observed
      influenza-related mortality. The model results indicate that direct modulation of
      influenza transmissibility by absolute humidity alone is sufficient to produce
      this observed seasonality. These findings provide epidemiological support for the
      hypothesis that absolute humidity drives seasonal variations of influenza
      transmission in temperate regions.

PMID- 20130781
TI  - Efficient simulation of the spatial transmission dynamics of influenza.
AB  - Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies
      over-estimated the within-country rate of spatial spread of pandemic influenza.
      As large spatially-resolved data sets are constructed, the need for efficient
      simulation code with which to investigate the spatial patterns of the pandemic
      becomes clear. Here, we describe a significant improvement in the efficiency of
      an individual-based stochastic disease simulation framework that has been used
      for multiple previous studies. We quantify the efficiency of the revised
      algorithm and present an alternative parameterization of the model in terms of
      the basic reproductive number. We apply the model to the population of Taiwan and
      demonstrate how the location of the initial seed can influence spatial incidence
      profiles and the overall spread of the epidemic. Differences in incidence are
      driven by the relative connectivity of alternate seed locations.

PMID- 20130781
TI  - Efficient simulation of the spatial transmission dynamics of influenza.
AB  - Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies
      over-estimated the within-country rate of spatial spread of pandemic influenza.
      As large spatially-resolved data sets are constructed, the need for efficient
      simulation code with which to investigate the spatial patterns of the pandemic
      becomes clear. Here, we describe a significant improvement in the efficiency of
      an individual-based stochastic disease simulation framework that has been used
      for multiple previous studies. We quantify the efficiency of the revised
      algorithm and present an alternative parameterization of the model in terms of
      the basic reproductive number. We apply the model to the population of Taiwan and
      demonstrate how the location of the initial seed can influence spatial incidence
      profiles and the overall spread of the epidemic. Differences in incidence are
      driven by the relative connectivity of alternate seed locations.

PMID- 20126277
TI  - Pandemic influenza 2009 on Reunion Island: A mild wave linked to a low
      reproduction number.
AB  - We studied the epidemic trend following the introduction of the pandemic A(H1N1)
      2009 in the subtropical Reunion Island. There, the pandemic wave started from
      week 30 and lasted until week 38, with an estimated attack rate of 12.85 % for
      symptomatic infections. The best estimate for the initial reproduction number was
      Ri = 1.26 [1.08; 1.49]. It results that the herd immunity necessary to stop the
      epidemic growth is of the same magnitude than the attack rate. Thus, a second
      wave before the 2010 austral winter seems unlikely, unless a viral mutation.

PMID- 20126278
TI  - Host Dependent Evolutionary Patterns and the Origin of 2009 H1N1 Pandemic
      Influenza.
AB  - The origin of H1N1pdm constitutes an unresolved mystery, as its most recently
      observed ancestors were isolated in pigs nearly a decade before it emerged in
      humans. One theory suggests imperfect surveillance of swine viruses caused the
      virus to be missed in swine herds. Other hypotheses point to the possibility of
      laboratory error or an avian intermediary. We show substitution bias
      classification identifies the host where a virus has been evolving. Comparing the
      evolution of H1N1pdm ancestors with other influenza viruses, we show the
      evolutionary history in unsampled years is similar to the evolution of other
      swine viruses, presenting evidence it emerged from unsampled herds.

PMID- 20126278
TI  - Host Dependent Evolutionary Patterns and the Origin of 2009 H1N1 Pandemic
      Influenza.
AB  - The origin of H1N1pdm constitutes an unresolved mystery, as its most recently
      observed ancestors were isolated in pigs nearly a decade before it emerged in
      humans. One theory suggests imperfect surveillance of swine viruses caused the
      virus to be missed in swine herds. Other hypotheses point to the possibility of
      laboratory error or an avian intermediary. We show substitution bias
      classification identifies the host where a virus has been evolving. Comparing the
      evolution of H1N1pdm ancestors with other influenza viruses, we show the
      evolutionary history in unsampled years is similar to the evolution of other
      swine viruses, presenting evidence it emerged from unsampled herds.

PMID- 20191082
TI  - Seroprevalence Following the Second Wave of Pandemic 2009 H1N1 Influenza.
AB  - BACKGROUND: In April 2009, a new pandemic strain of influenza infected thousands
      of persons in Mexico and the United States and spread rapidly worldwide. During
      the ensuing summer months, cases ebbed in the Northern Hemisphere while the
      Southern Hemisphere experienced a typical influenza season dominated by the novel
      strain. In the fall, a second wave of pandemic H1N1 swept through the United
      States, peaking in most parts of the country by mid October and returning to
      baseline levels by early December. The objective was to determine the
      seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by
      decade of birth among Pittsburgh-area residents. METHODS AND FINDINGS: Anonymous
      blood samples were obtained from clinical laboratories and categorized by decade
      of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately
      100 samples per decade (n= 846) were tested from blood samples drawn on hospital
      and clinic patients in mid-November and early December 2009. Age specific
      seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and
      compared to seroprevalences against H1N1 strains that had previously circulated
      in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957,
      and A/South Carolina/1/1918). Stored serum samples from healthy, young adults
      from 2008 were used as a control group (n=100). Seroprevalences against pandemic
      2009 H1N1 influenza varied by age group, with children age 10-19 years having the
      highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%).
      The baseline seroprevalence among control samples from 18-24 year-olds was 6%.
      Overall seroprevalence against pandemic H1N1 across all age groups was
      approximately 21%. CONCLUSIONS: After the peak of the second wave of 2009 H1N1,
      HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had
      become infected and developed immunity. Extrapolating to the entire US
      population, we estimate that at least 63 million persons became infected in 2009.
      As was observed among clinical cases, this sero-epidemiological study revealed
      highest infection rates among school-age children.

PMID- 20352039
TI  - Structure and Receptor binding properties of a pandemic H1N1 virus hemagglutinin.
AB  - The 3D-structure of the major surface viral antigen from the recent H1N1 pandemic
      influenza virus (A/Darwin/2001/2009) was determined to 2.8 A resolution. The
      structure was used to analyze changes in the HA that have emerged during the
      first 11 months of the pandemic and have raised public health concerns. Receptor
      binding properties of this protein reveals a strict preference for human-type
      receptors.

PMID- 20877455
TI  - Cognitive follow up of a small cohort of Huntington's disease patients over a 5
      year period.
AB  - A small group of patients with manifest Huntington's disease (HD) were followed
      longitudinally to assess cognitive decline in relation to time from disease
      diagnosis. This article looks at performance on a range of computerised and
      pencil and paper cognitive tasks in patients 5 years post diagnosis, who were
      assessed annually for a 5 year follow up period. The almost universal cognitive
      decline reported in other longitudinal studies of HD was not replicated in this
      study. It was proposed that longitudinal follow up in HD is complicated by the
      varying degree to which different tasks are able to withstand repeated
      administration; a finding which would have significant implications on study
      design in future trials of cognitive enhansing interventions.

PMID- 20877451
TI  - CYP2D6 testing to predict response to tamoxifen in women with breast cancer:
      Pharmacogenomic.
AB  - Tamoxifen, a selective estrogen receptor modulator, is the standard of care for
      premenopausal women with estrogen or progesterone receptor-positive breast cancer
      and a valid option for treating post-menopausal women. However, a substantial
      number of tamoxifen-treated patients relapse following surgical resection, while
      others remain disease-free for many years. It appears that the primary effectors
      of tamoxifen activity are its active metabolites, rather than tamoxifen itself.
      Cytochrome P450 (CYP) enzymes, CYP2D6 in particular, play a major role in the
      metabolism of tamoxifen to active metabolites. More than 75 germline CYP2D6
      variants have been identified. A test predicting lack of response to tamoxifen
      could supplement information used by clinicians and patients in treatment
      decision-making. For example, physicians and patients may opt to switch to an
      alternative therapy upfront.

PMID- 20972474
TI  - DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma
      Multiform.
AB  - It is estimated that approximately 22,000 Americans will be diagnosed with tumor
      of the brain or nervous system in 2010. Among primary brain tumors, approximately
      60% are gliomas, the most common and most malignant of which is glioblastoma
      multiforme (GBM).The DecisionDx-GBM test is a multigene expression assay that is
      designed to predict which patients are likely to experience long-term (> 2 years)
      progression-free survival.

PMID- 20972475
TI  - BRAF p.Val600Glu (V600E) Testing for Assessment of Treatment Options in
      Metastatic Colorectal Cancer.
AB  - Colon and rectal cancer (CRC) are the third most common cancer in the United
      States and cause approximately 50,000 deaths per year. The anti-epidermal growth
      factor receptor (EGFR) monoclonal antibodies cetuximab (Erbitux(r)) and
      panitumumab (Vectibix(r)) have been recently introduced to treat CRC. However,
      the response rate with these agents is low and they are associated with serious
      adverse effects. Accordingly biomarkers that can predict those patients that will
      respond to treatment may have clinical utility. The p.Val600Glu sequence variant
      (often called V600E) in the BRAF gene has been investigated as a biomarker to
      predict patients that will not respond to treatment with the anti-EGFR monoclonal
      antibodies.

PMID- 20981129
TI  - Serum levels of a subset of cytokines show high interindividual variability and
      are not altered in rats transgenic for Huntington's disease.
AB  - To evaluate whether cytokines are altered in peripheral blood of rats transgenic
      for the human Huntington's disease mutation we investigated serum levels of
      GRO/KC, IL-1beta, IL-13 and TNF-alpha at a symptomatic stage at 12 months of age.
      Overall serum levels of these cytokines were not significantly changed between
      transgenic HD rats and controls. Moreover, we observed a high interindividual
      variability. Our results indicate that these cytokines will be difficult to
      pursue as biomarkers in at least this rat model of HD.

PMID- 20975779
TI  - KIF6 p.Trp719Arg Testing to Assess Risk of Coronary Artery Disease and/or Statin
      Response.
AB  - Coronary artery disease (CAD) is a leading cause of death worldwide and in the
      United States it is responsible for more than 500,000 deaths each year. Genome
      wide association studies (GWAS) have revealed connections between a number of
      common single nucleotide polymorphisms (SNPs) and CAD and other cardiovascular
      diseases. The p.Trp719Arg SNP in the kinesin-like family 6 (KIF6) gene has
      recently been reported as a potential risk factor for CAD as well as a predictor
      of response to statin therapy.

PMID- 21113336
TI  - Are node-based and stem-based clades equivalent? Insights from graph theory.
AB  - Despite the prominence of "tree-thinking" among contemporary systematists and
      evolutionary biologists, the biological meaning of different mathematical
      representations of phylogenies may still be muddled. We compare two basic kinds
      of discrete mathematical models used to portray phylogenetic relationships among
      species and higher taxa: stem-based trees and node-based trees. Each model is a
      tree in the sense that is commonly used in mathematics; the difference between
      them lies in the biological interpretation of their vertices and edges. Stem
      based and node-based trees carry exactly the same information and the biological
      interpretation of each is similar. Translation between these two kinds of trees
      can be accomplished by a simple algorithm, which we provide. With the
      mathematical representation of stem-based and node-based trees clarified, we
      argue for a distinction between types of trees and types of names. Node-based and
      stem-based trees contain exactly the same information for naming clades. However,
      evolutionary concepts, such as monophyly, are represented as different
      mathematical substructures in the two models. For a given stem-based tree, one
      should employ stem-based names, whereas for a given node-based tree, one should
      use node-based names, but applying a node-based name to a stem-based tree is not
      logical because node-based names cannot exist on a stem-based tree and visa
      versa. Authors might use node-based and stem-based concepts of monophyly for the
      same representation of a phylogeny, yet, if so, they must recognize that such a
      representation differs from the graphical models used for computing in
      phylogenetic systematics.

PMID- 21113337
TI  - New insights into the phylogeny and historical biogeography of the Lellingeria
      myosuroides clade (Polypodiaceae).
AB  - Grammitid ferns are a well-supported clade of ~900 primarily tropical epiphytic
      species. Recent phylogenetic studies have found support for a distinctive,
      geographically diverse group of 24 species referred to as the Lellingeria
      myosuroides clade and have provided evidence for a variety of phylogenetic
      relationships within the group, as well as hypotheses of historical processes
      that have produced current biogeographical patterns. We present new data and
      analyses that support the following primary conclusions: 1) the L. myosuroides
      clade is monophyletic and pantropical; 2) that clade is sister to a more species
      rich clade of entirely Neotropical species (Lellingeria s.s.); 3) we infer two
      independent dispersal events from the Neotropics to Pacific islands, five
      independent dispersal events from the Neotropics to the Paleotropics, and two
      separate dispersal events from mainland tropical America to the West Indies.

PMID- 20890398
TI  - Observing Huntington's Disease: the European Huntington's Disease Network's
      REGISTRY.
AB  - BACKGROUND: Huntington's disease (HD) is a rare triplet repeat (CAG) disorder.
      Advanced, multi-centre, multi-national research frameworks are needed to study
      simultaneously multiple complementary aspects of HD. This includes the natural
      history of HD, its management and the collection of clinical information and
      biosamples for research. METHODS: We report on cross-sectional data of the first
      1766 participants in REGISTRY, the European Huntington's Disease Network's
      (EHDN), multi-lingual, multi-national prospective observational study of HD in
      Europe. Data collection (demographics, phenotype, genotype, medication, co
      morbidities, biosamples) followed a standard protocol. RESULTS: Phenotype, and
      the HD genotype, of manifest HD participants across different European regions
      was similar. Motor onset was most common (48%) with a non-motor onset in more
      than a third of participants. Motor signs increased, and cognitive abilities and
      functional capacity declined as the disease burden (CAGn-35.5) X age) increased.
      A life-time history of behavioural symptoms was common, but the behavioural score
      was not related to disease burden. One fifth of participants had severe
      psychiatric problems, e.g. suicidal ideation and attempts, and/or
      irritability/aggression, with psychosis being less common. Participants on anti
      dyskinetic medication had a higher motor and lower cognitive score, were older,
      and more prone to physical trauma. A higher motor and a lower cognitive score
      predicted more advanced disease. CONCLUSIONS: The unparalleled collection of
      clinical data and biomaterials within the EHDN's REGISTRY can expedite the search
      for disease modifiers (genetic and environmental) of age at onset and disease
      progression that could be harnessed for the development of novel treatments.

PMID- 21113338
TI  - Multiple sequence alignment: a major challenge to large-scale phylogenetics.
AB  - Over the last decade, dramatic advances have been made in developing methods for
      large-scale phylogeny estimation, so that it is now feasible for investigators
      with moderate computational resources to obtain reasonable solutions to maximum
      likelihood and maximum parsimony, even for datasets with a few thousand
      sequences. There has also been progress on developing methods for multiple
      sequence alignment, so that greater alignment accuracy (and subsequent
      improvement in phylogenetic accuracy) is now possible through automated methods.
      However, these methods have not been tested under conditions that reflect
      properties of datasets confronted by large-scale phylogenetic estimation
      projects. In this paper we report on a study that compares several alignment
      methods on a benchmark collection of nucleotide sequence datasets of up to 78,132
      sequences. We show that as the number of sequences increases, the number of
      alignment methods that can analyze the datasets decreases. Furthermore, the most
      accurate alignment methods are unable to analyze the very largest datasets we
      studied, so that only moderately accurate alignment methods can be used on the
      largest datasets. As a result, alignments computed for large datasets have
      relatively large error rates, and maximum likelihood phylogenies computed on
      these alignments also have high error rates. Therefore, the estimation of highly
      accurate multiple sequence alignments is a major challenge for Tree of Life
      projects, and more generally for large-scale systematics studies.

PMID- 21113338
TI  - Multiple sequence alignment: a major challenge to large-scale phylogenetics.
AB  - Over the last decade, dramatic advances have been made in developing methods for
      large-scale phylogeny estimation, so that it is now feasible for investigators
      with moderate computational resources to obtain reasonable solutions to maximum
      likelihood and maximum parsimony, even for datasets with a few thousand
      sequences. There has also been progress on developing methods for multiple
      sequence alignment, so that greater alignment accuracy (and subsequent
      improvement in phylogenetic accuracy) is now possible through automated methods.
      However, these methods have not been tested under conditions that reflect
      properties of datasets confronted by large-scale phylogenetic estimation
      projects. In this paper we report on a study that compares several alignment
      methods on a benchmark collection of nucleotide sequence datasets of up to 78,132
      sequences. We show that as the number of sequences increases, the number of
      alignment methods that can analyze the datasets decreases. Furthermore, the most
      accurate alignment methods are unable to analyze the very largest datasets we
      studied, so that only moderately accurate alignment methods can be used on the
      largest datasets. As a result, alignments computed for large datasets have
      relatively large error rates, and maximum likelihood phylogenies computed on
      these alignments also have high error rates. Therefore, the estimation of highly
      accurate multiple sequence alignments is a major challenge for Tree of Life
      projects, and more generally for large-scale systematics studies.

PMID- 21127722
TI  - Tempo and mode in the molecular evolution of influenza C.
AB  - Influenza C contributes to economic damage caused by working days lost through
      absence or inefficiency and may occasionally cause an acute respiratory illness
      in a paediatric setting. All Influenza C sequences from the NCBI Influenza Virus
      Resource were examined to determine the date of the most recent common ancestor
      (t-MRCA), the average nucleotide substitution rate, and the location of residues
      under positive selection, for each of the seven genome segments of this virus.
      The segment with the deepest phylogeny was found to be segment 4, encoding the
      haemagglutinin-esterase protein (HE) with mean t-MRCA at 1890 of the common era
      (AD), at a 95% highest posterior density (HPD) of 1857-1924 AD. Other genome
      segments have slightly more recent common ancestors, ranging from mean t-MRCAs of
      1916 AD (HPD 1891-1937) for segment 7, encoding the two non-structural proteins
      (NS) to 1944 AD (HPD 1940-1948) for segment 2 encoding the type 1 basic
      polymerase (PB1). On the basis of the Bayesian analysis a reclassification of
      lineages within genome segments is proposed. Some evidence for positive selection
      was found in the receptor-binding domain of the haemagglutinin-esterase protein.
      However, average omega (omega) values ranged from 0.05 for polymerase basic
      protein 2 (PB2) to 0.38 for non-structural protein 2 (NS2), suggesting that
      strong to moderate purifying selection is the main trend. Characteristic
      combinations of segment lineages were identified (genome constellations) and
      shown to have a relatively short life-span before being broken up by
      reassortment.

PMID- 21188137
TI  - BCR-ABL mutation testing to predict response to tyrosine kinase inhibitors in
      patients with chronic myeloid leukemia.
AB  - Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic
      myeloid leukemia (CML). Although randomized evidence demonstrates that imatinib
      (a commercially available TKI) prolongs event-free survival in patients with CML,
      some patients develop imatinib intolerance or resistance. In addition, imatinib
      is less effective in patients who have progressed to more advanced disease
      stages, such as accelerated phase and blastic phase CML. For these reasons, 2nd
      generation TKIs that can inhibit the BCR-ABL protein more effectively or target
      additional disease mechanisms have been developed. Two such drugs have also been
      approved for clinical use by the FDA, nilotinib and dasatinib. Resistance to TKI
      treatment is thought to be mediated through various mechanisms, the most common
      of which is BCR-ABL1 mutations. Testing for mutations in BCR-ABL1 may predict
      lack of response to imatinib or may inform the choice between alternative TKIs.

PMID- 21804956
TI  - Assessment of motor symptoms and functional impact in prodromal and early
      huntington disease.
AB  - The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a
      multinational, multidisciplinary initiative with the goal of developing a data
      driven, comprehensive, psychometrically sound, rating scale for assessing
      symptoms and functional ability in prodromal and early Huntington disease (HD)
      gene expansion carriers. The process involves input from numerous sources to
      identify relevant symptom domains, including HD individuals, caregivers, and
      experts from a variety of fields, as well as knowledge gained from the analysis
      of data from ongoing large-scale studies in HD using existing clinical scales.
      This is an iterative process in which an ongoing series of field tests in
      prodromal (prHD) and early HD individuals provides the team with data on which to
      make decisions regarding which questions should undergo further development or
      testing and which should be excluded. We report here the development and
      assessment of the first iteration of interview questions aimed to assess
      functional impact of motor manifestations in prHD and early HD individuals.

PMID- 20029612
TI  - Top-hits for H1N1pdm Identified by Virtual Screening Using Ensemble-based
      Docking.
AB  - A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm
      strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of
      the bird flu H5N1, an effective means to quickly identify top candidates for use
      against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI
      diversity set which bind best to H5N1 neuraminidase. These compounds serve as
      viable candidates for docking against the H1N1pdm neuraminidase, using ensembles
      extracted from molecular dynamics simulations of the H1N1pdm system. The ranking
      order of these top candidates was found to be different from the previously
      published results for H5N1. The results indicated that the Oseltamivir (Tamiflu)
      and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six
      drug candidates were found to bind more effectively to H1N1pdm neuraminidase than
      Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also
      provided.

PMID- 21379361
TI  - Body composition in premanifest Huntington's disease reveals lower bone density
      compared to controls.
AB  - Huntington's disease (HD) is a debilitating autosomal dominant, neurodegenerative
      disease with a fatal prognosis. Classical features include motor disturbances,
      dementia and psychiatric problems but are not restricted to this triad as
      patients often experience other abnormalities such as unintended weight loss, the
      exact cause of which is unknown. We studied the body composition of 25
      premanifest HD and compared it to 25 control subjects using a dual energy x-ray
      absorptiometer (DEXA) scan. Like the R6/2 transgenic mouse model, we identified
      significantly lower bone mineral density z-scores in premanifest individuals,
      that was not related to any difference in testosterone, cortisol, leptin or
      Vitamin D levels. These results identify an early gene-related change that occurs
      in HD which not only could lead to a potential biomarker for the disease, but
      given it is also seen in other manifest neurodegenerative diseases, could also
      reveal a common disease related process.

PMID- 21436956
TI  - Phylogenetic discordance of human and canine carcinoembryonic antigen (CEA,
      CEACAM) families, but striking identity of the CEA receptors will impact
      comparative oncology studies.
AB  - Comparative oncology aims at speeding up developments for both, human and
      companion animal cancer patients. Following this line, carcinoembryonic antigen
      (CEA, CEACAM5) could be a therapeutic target not only for human but also for
      canine (Canis lupus familiaris; dog) patients. CEACAM5 interacts with CEA
      receptor (CEAR) in the cytoplasm of human cancer cells. Our aim was, therefore,
      to phylogenetically verify the antigenic relationship of CEACAM molecules and
      CEAR in human and canine cancer.Anti-human CEACAM5 antibody Col-1, previously
      being applied for cancer diagnosis in dogs, immunohistochemically reacted to 23
      out of 30 canine mammary cancer samples. In immunoblot analyses Col-1
      specifically detected human CEACAM5 at 180 kDa in human colon cancer cells HT29,
      and the canine antigen at 60, 120, or 180 kDa in CF33 and CF41 mammary carcinoma
      cells as well as in spontaneous mammary tumors. While according to phylogenicity
      canine CEACAM1 molecules should be most closely related to human CEACAM5, Col-1
      did not react with canine CEACAM1, -23, -24, -25, -28 or -30 transfected to
      canine TLM-1 cells. By flow cytometry the Col-1 target molecule was localized
      intracellularly in canine CF33 and CF41 cells, in contrast to membranous and
      cytoplasmic expression of human CEACAM5 in HT29. Col-1 incubation had neither
      effect on canine nor human cancer cell proliferation. Yet, Col-1 treatment
      decreased AKT-phosphorylation in canine CF33 cells possibly suggestive of anti
      apoptotic function, whereas Col-1 increased AKT-phosphorylation in human HT29
      cells. We report further a 99% amino acid similarity of human and canine CEA
      receptor (CEAR) within the phylogenetic tree. CEAR could be detected in four
      canine cancer cell lines by immunoblot and intracellularly in 10 out of 10
      mammary cancer specimens from dog by immunohistochemistry. Whether the specific
      canine Col-1 target molecule may as functional analogue to human CEACAM5 act as
      ligand to canine CEAR, remains to be defined. This study demonstrates the
      limitations of comparative oncology due to the complex functional evolution of
      the different CEACAM molecules in humans versus dogs. In contrast, CEAR may be a
      comprehensive interspecies target for novel cancer therapeutics.

PMID- 21894257
TI  - Applying a New Model for Sharing Population Health Data to National Syndromic
      Influenza Surveillance: DiSTRIBuTE Project Proof of Concept, 2006 to 2009.
AB  - The Distributed Surveillance Taskforce for Real-time Influenza Burden Tracking
      and Evaluation (DiSTRIBuTE) project began as a pilot effort initiated by the
      International Society for Disease Surveillance (ISDS) in autumn 2006 to create a
      collaborative electronic emergency department (ED) syndromic influenza-like
      illness (ILI) surveillance network based on existing state and local systems and
      expertise. DiSTRIBuTE brought together health departments that were interested
      in: 1) sharing aggregate level data; 2) maintaining jurisdictional control; 3)
      minimizing barriers to participation; and 4) leveraging the flexibility of local
      systems to create a dynamic and collaborative surveillance network. This approach
      was in contrast to the prevailing paradigm for surveillance where record level
      information was collected, stored and analyzed centrally. The DiSTRIBuTE project
      was created with a distributed design, where individual level data remained local
      and only summarized, stratified counts were reported centrally, thus minimizing
      privacy risks. The project was responsive to federal mandates to improve
      integration of federal, state, and local biosurveillance capabilities. During the
      proof of concept phase, 2006 to 2009, ten jurisdictions from across North America
      sent ISDS on a daily to weekly basis year-round, aggregated data by day,
      stratified by local ILI syndrome, age-group and region. During this period, data
      from participating U.S. state or local health departments captured over 13% of
      all ED visits nationwide. The initiative focused on state and local health
      department trust, expertise, and control. Morbidity trends observed in DiSTRIBuTE
      were highly correlated with other influenza surveillance measures. With the
      emergence of novel A/H1N1 influenza in the spring of 2009, the project was used
      to support information sharing and ad hoc querying at the state and local level.
      In the fall of 2009, through a broadly collaborative effort, the project was
      expanded to enhance electronic ED surveillance nationwide.

PMID- 21975581
TI  - An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea
      in Huntington's Disease.
AB  - It is generally believed that treatments are available to manage chorea in
      Huntington's disease (HD). However, lack of evidence prevents the establishment
      of treatment guidelines. The HD chorea research literature fails to address the
      indications for drug treatment, drug selection, drug dosing and side effect
      profiles, management of inadequate response to a single drug, and preferred drug
      when behavioral symptoms comorbid to chorea are present. Because there is lack of
      an evidence base to inform clinical decision-making, we surveyed an international
      group of experts to address these points. Survey results showed that patient
      stigma, physical injury, gait instability, work interference, and disturbed sleep
      were indications for a drug treatment trial. However, the experts did not agree
      on first choice of chorea drug, with the majority of experts in Europe favoring
      an antipsychotic drug (APD), and a near equal split in first choice between an
      APD and tetrabenazine (TBZ) among experts from North America and Australia. All
      experts chose an APD when comorbid psychotic or aggressive behaviors were
      present, or when active depression prevented the use of TBZ. However, there was
      agreement from all geographic regions that both APDs and TBZ were acceptable as
      monotherapy in other situations. Perceived efficacy and side effect profiles were
      similar for APDs and TBZ, except for depression as a significant side effect of
      TBZ. Experts used a combination of an APD and TBZ when treatment required both
      drugs for control of chorea and a concurrent comorbid symptom, or when severe
      chorea was inadequately controlled by either drug alone. The benzodiazepines
      (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy,
      particularly when chorea was exacerbated by anxiety. There was broad disagreement
      about the use of amantadine for chorea. Experts who had used amantadine described
      its benefit as small and transient. In addition to survey results, this report
      reviews available chorea studies, and lastly presents an algorithm for the
      treatment of chorea in HD which is based on expert preferences obtained through
      this international survey.

PMID- 22379024
TI  - Proinflammatory characteristics of SMAC/DIABLO-induced cell death in antitumor
      therapy.
AB  - Molecular mimetics of the caspase activator second mitochondria-derived activator
      of caspase (SMAC) are being investigated for use in cancer therapy, but an
      understanding of in vivo effects remains incomplete. In this study, we offer
      evidence that SMAC mimetics elicit a proinflammatory cell death in cancer cells
      that engages an adaptive antitumor immune response. Cancer cells of different
      histologic origin underwent apoptosis when transduced with lentiviral vectors
      encoding a cytosolic form of the SMAC mimetic LV-tSMAC. Strikingly, treatment of
      tumor-bearing mice with LV-tSMAC resulted in the induction of apoptosis,
      activation of antitumor immunity, and enhanced survival. Antitumor immunity was
      accompanied by an increase of tumor-infiltrating lymphocytes displaying low PD-1
      expression, high lytic capacity, and high levels of IFN-gamma when stimulated. We
      also noted in vivo a decrease in regulatory T cells along with in vitro
      activation of tumor-specific CD8(+) T cells by dendritic cells (DC) isolated from
      tumor draining lymph nodes. Last, tumor-specific cytotoxic T cells were also
      found to be activated in vivo. Mechanistic analyses showed that transduction of
      cancer cells with LV-tSMAC resulted in exposure of calreticulin but not release
      of HMGB1 or ATP. Nevertheless, DCs were activated upon engulfment of dying cancer
      cells. Further validation of these findings was obtained by their extension in a
      model of human melanoma using transcriptionally targeted LV-tSMAC. Together, our
      findings suggest that SMAC mimetics can elicit a proinflammatory cell death that
      is sufficient to activate adaptive antitumor immune responses in cancer.

PMID- 22379025
TI  - Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.
AB  - Grainyhead genes are involved in wound healing and developmental neural tube
      closure. In light of the high degree of similarity between the epithelial
      mesenchymal transitions (EMT) occurring in wound-healing processes and the cancer
      stem cell-like compartment of tumors, including TGF-beta dependence, we
      investigated the role of the Grainyhead gene, Grainyhead-like-2 (GRHL2) in
      oncogenic EMT. GRHL2 was downregulated specifically in the claudin-low subclass
      breast tumors and in basal-B subclass breast cancer cell lines. GRHL2 suppressed
      TGF-beta-induced, Twist-induced or spontaneous EMT, enhanced anoikis sensitivity,
      and suppressed mammosphere generation in mammary epithelial cells. These effects
      were mediated in part by suppression of ZEB1 expression via direct repression of
      the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription and it
      upregulated mir-200b/c as well as the TGF-beta receptor antagonist, BMP2.
      Finally, ectopic expression of GRHL2 in MDA-MB-231 breast cancer cells triggered
      an MET and restored sensitivity to anoikis. Taken together, our findings define a
      major role for GRHL2 in the suppression of oncogenic EMT in breast cancer cells.

PMID- 22379026
TI  - Two-compartment model of NK cell proliferation: insights from population response
      to IL-15 stimulation.
AB  - NK cells are innate lymphocytes that mediate early host defense against viruses,
      such as cytomegalovirus. IL-15 is upregulated during viral infections and drives
      the expansion of NK cells. However, the influence of IL-15 on murine NK cell
      division and death rates has not been quantitatively studied. Therefore, we
      developed a series of two-compartment (representing quiescent and dividing NK
      cell subpopulations) mathematical models, incorporating different assumptions
      about the kinetic parameters regulating NK cell expansion. Using experimentally
      derived division and death rates, we tested each model's assumptions by comparing
      predictions of NK cell numbers with independent experimental results and
      demonstrated that the kinetic parameters are distinct for nondividing and
      dividing NK cell subpopulations. IL-15 influenced NK cell expansion by modulating
      recruitment and division rates to a greater extent than death rates. The observed
      time delay to first division could be accounted for by differences in the kinetic
      parameters of nondividing and dividing subsets of NK cells. Although the duration
      of the time delay to first division was not significantly influenced by IL-15,
      the recruitment of nondividing NK cells into the replicating subpopulation
      increased with greater IL-15 concentrations. Our model quantitatively predicted
      changes in NK cell accumulation when IL-15 stimulation was reduced, demonstrating
      that NK cell divisional commitment was interrupted when cytokine stimulation was
      removed. In summary, this quantitative analysis reveals novel insights into the
      in vitro regulation of NK cell proliferation and provides a foundation for
      modeling in vivo NK cell responses to viral infections.

PMID- 22379027
TI  - Follicular helper NKT cells induce limited B cell responses and germinal center
      formation in the absence of CD4(+) T cell help.
AB  - B cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement
      by CD4(+) T follicular helper (T(FH)) cells to form germinal centers and long
      lasting Ab responses. Invariant NKT (iNKT) cells are innate-like lymphocytes that
      jumpstart the adaptive immune response when activated by the CD1d-restricted
      lipid alpha-galactosylceramide (alphaGalCer). We previously observed that
      immunization of mice lacking CD4(+) T cells (MHC II(-/-)) elicits specific IgG
      responses only when protein Ags are mixed with alphaGalCer. In this study, we
      investigated the mechanisms underpinning this observation. We find that induction
      of Ag-specific Ab responses in MHC II(-/-) mice upon immunization with protein
      Ags mixed with alphaGalCer requires CD1d expression and CD40 engagement on B
      cells, suggesting that iNKT cells provide CD1d-restricted cognate help for B
      cells. Remarkably, splenic iNKT cells from immunized MHC II(-/-) mice display a
      typical CXCR5(hi)programmed death-1(hi)ICOS(hi)Bcl-6(hi) T(FH) phenotype and
      induce germinal centers. The specific IgG response induced in MHC II(-/-) mice
      has shorter duration than that developing in CD4-competent animals, suggesting
      that iNKT(FH) cells preferentially induce transient rather than long-lived Ab
      responses. Together, these results suggest that iNKT cells can be co-opted into
      the follicular helper function, yet iNKT(FH) and CD4(+) T(FH) cells display
      distinct helper features, consistent with the notion that these two cell subsets
      play nonredundant functions throughout immune responses.

PMID- 22379028
TI  - Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T
      cell responses for tumor immunity.
AB  - Vaccine strategies aimed at generating CD8(+) T cell memory responses are likely
      to show augmented efficacy against chronic challenges like tumor. The abundance
      in variety of memory CD8(+) T cells behooves development of vaccine strategies
      that generate distinct memory responses and evaluate them for tumor efficacy. In
      this study, we demonstrate the ability of a variety of rapamycin treatment
      regimens to regulate virus vaccination-induced CD8(+) T cell memory responses and
      tumor efficacy. Strikingly, a short course of high-dose, but not low-dose,
      rapamycin treatment transiently blocks viral vaccination-induced mammalian target
      of rapamycin activity in CD8(+) T cells favoring persistence and Ag-recall
      responses over type 1 effector maturation; however, prolonged high-dose rapamycin
      administration abrogated memory responses. Furthermore, a short course of high
      dose rapamycin treatment generated CD8(+) T cell memory responses that were
      independent of IL-15 and IL-7 and were programmed early for sustenance and
      greater tumor efficacy. These results demonstrate the impact a regimen of
      rapamycin treatment has on vaccine-induced CD8(+) T cell responses and indicates
      that judicious application of rapamycin can augment vaccine efficacy for chronic
      challenges.

PMID- 22379029
TI  - TGF-beta-mediated downregulation of microRNA-196a contributes to the constitutive
      upregulated type I collagen expression in scleroderma dermal fibroblasts.
AB  - Previous reports indicated the significance of the TGF-beta signaling in the
      pathogenesis of systemic sclerosis. We tried to evaluate the possibility that
      microRNAs (miRNAs) play a part in the type I collagen upregulation seen in normal
      fibroblasts stimulated with exogenous TGF-beta and systemic sclerosis (SSc)
      fibroblasts. miRNA expression profile was evaluated by miRNA PCR array and real
      time PCR. The protein expression of type I collagen was determined by
      immunoblotting. In vivo detection of miRNA in paraffin section was performed by
      in situ hybridization. Several miRNAs were found to be downregulated in both TGF
      beta-stimulated normal fibroblasts and SSc fibroblasts compared with normal
      fibroblasts by PCR array. Among them, miR-196a expression was decreased in SSc
      both in vivo and in vitro by real-time PCR or in situ hybridization. In SSc
      fibroblasts, miR-196a expression was normalized by TGF-beta small interfering
      RNA. miR-196a inhibitor leads to the overexpression of type I collagen in normal
      fibroblasts, whereas overexpression of the miRNA resulted in the downregulation
      of type I collagen in SSc fibroblasts. In addition, miR-196a was detectable and
      quantitative in the serum of SSc patients. Patients with lower serum miR-196a
      levels had significantly higher ratio of diffuse cutaneous SSc:limited cutaneous
      SSc, higher modified Rodnan total skin thickness score, and higher prevalence of
      pitting scars than those without. miR-196a may play some roles in the
      pathogenesis of SSc. Investigation of the regulatory mechanisms of type I
      collagen expression by miR-196a may lead to new treatments using miRNA.

PMID- 22379030
TI  - IL-17A differentially regulates corneal vascular endothelial growth factor (VEGF)
      A and soluble VEGF receptor 1 expression and promotes corneal angiogenesis after
      herpes simplex virus infection.
AB  - Ocular infection with HSV causes corneal neovascularization (CV), an essential
      step in the pathogenesis of the blinding immunoinflammatory lesion stromal
      keratitis. The infection results in IL-17A production, which contributes to CV in
      ways that together serve to shift the balance between corneal concentrations of
      vascular endothelial growth factor A (VEGF-A) and the soluble vascular
      endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks
      its function (a so-called VEGF trap). Accordingly, animals lacking responses to
      IL-17A signaling, either because of IL-17 receptor A knockout or wild-type
      animals that received neutralizing mAb to IL-17A, had diminished CV, compared
      with controls. The procedures reduced VEGF-A protein levels but had no effect on
      the levels of soluble vascular endothelial growth factor receptor 1. Hence the
      VEGF trap was strengthened. IL-17A also caused increased CXCL1/KC synthesis,
      which attracts neutrophils to the inflammatory site. Neutrophils further
      influenced the extent of CV by acting as an additional source of VEGF-A, as did
      metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF
      blocking activity. Our results indicate that suppressing the expression of IL
      17A, or increasing the activity of the VEGF trap, represents a useful approach to
      inhibiting CV and the control of an ocular lesion that is an important cause of
      human blindness.

PMID- 22379031
TI  - Dynamic microRNA gene transcription and processing during T cell development.
AB  - By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway
      is critical for the differentiation and function of T cells. Although various
      cloning studies have shown that many miRNAs are expressed during T cell
      development, and in a dynamic manner, it was unclear how comprehensive these
      earlier analyses were. We therefore decided to profile miRNA expression by next
      generation sequencing. Furthermore, we profiled miRNA expression starting from
      the hematopoietic stem cell. This analysis revealed that miRNA expression during
      T cell development is extremely dynamic, with 645 miRNAs sequenced, and the
      expression of some varying by as much as 3 orders of magnitude. Furthermore,
      changes in precursor processing led to altered mature miRNA sequences. We also
      analyzed the structures of the primary miRNA transcripts expressed in T cells and
      found that many were extremely long. The longest was pri-mir-29b-1/29a at ~168
      kb. All the long pri-miRNAs also displayed extensive splicing. Our findings
      indicate that miRNA expression during T cell development is both a highly dynamic
      and a highly regulated process.

PMID- 22379032
TI  - Differential risk of tuberculosis reactivation among anti-TNF therapies is due to
      drug binding kinetics and permeability.
AB  - Increased rates of tuberculosis (TB) reactivation have been reported in humans
      treated with TNF-alpha (TNF)-neutralizing drugs, and higher rates are observed
      with anti-TNF Abs (e.g., infliximab) as compared with TNF receptor fusion protein
      (etanercept). Mechanisms driving differential reactivation rates and differences
      in drug action are not known. We use a computational model of a TB granuloma
      formation that includes TNF/TNF receptor dynamics to elucidate these mechanisms.
      Our analyses yield three important insights. First, drug binding to membrane
      bound TNF critically impairs granuloma function. Second, a higher risk of
      reactivation induced from Ab-type treatments is primarily due to differences in
      TNF/drug binding kinetics and permeability. Apoptotic and cytolytic activities of
      Abs and pharmacokinetic fluctuations in blood concentration of drug are not
      essential to inducing TB reactivation. Third, we predict specific host factors
      that, if augmented, would improve granuloma function during anti-TNF therapy. Our
      findings have implications for the development of safer anti-TNF drugs to treat
      inflammatory diseases.

PMID- 22379033
TI  - MicroRNA-deficient NK cells exhibit decreased survival but enhanced function.
AB  - NK cells are innate immune lymphocytes important for early host defense against
      infectious pathogens and malignant transformation. MicroRNAs (miRNAs) are small
      RNA molecules that regulate a wide variety of cellular processes, typically by
      specific complementary targeting of the 3'UTR of mRNAs. The Dicer1 gene encodes a
      conserved enzyme essential for miRNA processing, and Dicer1 deficiency leads to a
      global defect in miRNA biogenesis. In this study, we report a mouse model of
      lymphocyte-restricted Dicer1 disruption to evaluate the role of Dicer1-dependent
      miRNAs in the development and function of NK cells. As expected, Dicer1-deficient
      NK cells had decreased total miRNA content. Furthermore, miRNA-deficient NK cells
      exhibited reduced survival and impaired maturation defined by cell surface
      phenotypic markers. However, Dicer1-deficient NK cells exhibited enhanced
      degranulation and IFN-gamma production in vitro in response to cytokines, tumor
      target cells, and activating NK cell receptor ligation. Moreover, a similar
      phenotype of increased IFN-gamma was evident during acute MCMV infection in vivo.
      miRs-15a/15b/16 were identified as abundant miRNAs in NK cells that directly
      target the murine IFN-gamma 3'UTR, thereby providing a potential mechanism for
      enhanced IFN-gamma production. These data suggest that the function of miRNAs in
      NK cell biology is complex, with an important role in NK cell development,
      survival, or homeostasis, while tempering peripheral NK cell activation. Further
      study of individual miRNAs in an NK cell specific fashion will provide insight
      into these complex miRNA regulatory effects in NK cell biology.

PMID- 22379034
TI  - Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17
      mediated immunity.
AB  - Dendritic cells (DCs) are responsible for priming T cells and for promoting their
      differentiation from naive T cells into appropriate effector cells. Emerging
      evidence suggests that neurotransmitters can modulate T cell-mediated immunity.
      However, the involvement of specific neurotransmitters or receptors remains
      poorly understood. In this study, we analyzed the role of dopamine in the
      regulation of DC function. We found that DCs express dopamine receptors as well
      as the machinery necessary to synthesize, store, and degrade dopamine. Notably,
      the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R
      on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and
      consequently attenuated the activation and proliferation of Ag-specific CD4(+) T
      cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the
      role of this receptor in the modulation of a CD4(+) T cell-driven autoimmunity
      model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type
      recipients were able to reduce the severity of experimental autoimmune
      encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed
      a significant reduction in the percentage of Th17 cells infiltrating the CNS
      without differences in the percentage of Th1 cells compared with animals
      transferred with wild-type DCs. Our findings demonstrate that by contributing to
      CD4(+) T cell activation and differentiation to Th17 phenotype, D5R expressed on
      DCs is able to modulate the development of an autoimmune response in vivo.

PMID- 22379035
TI  - Intrapulmonary administration of leukotriene B(4) augments neutrophil
      accumulation and responses in the lung to Klebsiella infection in CXCL1 knockout
      mice.
AB  - In prior studies, we demonstrated that 1) CXCL1/KC is essential for NF-kappaB and
      MAPK activation and expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine
      in Klebsiella-infected lungs, and 2) CXCL1 derived from hematopoietic and
      resident cells contributes to host immunity against Klebsiella. However, the role
      of CXCL1 in mediating neutrophil leukotriene B(4) (LTB(4)), reactive oxygen
      species (ROS), and reactive nitrogen species (RNS) production is unclear, as is
      the contribution of these factors to host immunity. In this study, we
      investigated 1) the role of CXCL1 in LTB(4), NADPH oxidase, and inducible NO
      synthase (iNOS) expression in lungs and neutrophils, and 2) whether LTB(4)
      postinfection reverses innate immune defects in CXCL1(-/-) mice via regulation of
      NADPH oxidase and iNOS. Our results demonstrate reduced neutrophil influx,
      attenuated LTB(4) levels, and decreased ROS and iNOS production in the lungs of
      CXCL1(-/-) mice after Klebsiella pneumoniae infection. Using neutrophil depletion
      and repletion, we found that neutrophils are the predominant source of pulmonary
      LTB(4) after infection. To treat immune defects in CXCL1(-/-) mice, we
      intrapulmonarily administered LTB(4). Postinfection, LTB(4) treatment reversed
      immune defects in CXCL1(-/-) mice and improved survival, neutrophil recruitment,
      cytokine/chemokine expression, NF-kappaB/MAPK activation, and ROS/RNS production.
      LTB(4) also enhanced myeloperoxidase, H(2)O(2,) RNS production, and bacterial
      killing in K. pneumoniae-infected CXCL1(-/-) neutrophils. These novel results
      uncover important roles for CXCL1 in generating ROS and RNS in neutrophils and in
      regulating host immunity against K. pneumoniae infection. Our findings suggest
      that LTB(4) could be used to correct defects in neutrophil recruitment and
      function in individuals lacking or expressing malfunctional CXCL1.

PMID- 22379036
TI  - ERK2-dependent activation of c-Jun is required for nontypeable Haemophilus
      influenzae-induced CXCL2 upregulation in inner ear fibrocytes.
AB  - The inner ear, composed of the cochlea and the vestibule, is a specialized
      sensory organ for hearing and balance. Although the inner ear has been known as
      an immune-privileged organ, there is emerging evidence indicating an active
      immune reaction of the inner ear. Inner ear inflammation can be induced by the
      entry of proinflammatory molecules derived from middle ear infection. Because
      middle ear infection is highly prevalent in children, middle ear infection
      induced inner ear inflammation can impact the normal development of language and
      motor coordination. Previously, we have demonstrated that the inner ear
      fibrocytes (spiral ligament fibrocytes) are able to recognize nontypeable
      Haemophilus influenzae, a major pathogen of middle ear infection, and upregulate
      a monocyte-attracting chemokine through TLR2-dependent NF-kappaB activation. In
      this study, we aimed to determine the molecular mechanism involved in nontypeable
      H. influenzae-induced cochlear infiltration of polymorphonuclear cells. The rat
      spiral ligament fibrocytes were found to release CXCL2 in response to nontypeable
      H. influenzae via activation of c-Jun, leading to the recruitment of
      polymorphonuclear cells to the cochlea. We also demonstrate that MEK1/ERK2
      signaling pathway is required for nontypeable H. influenzae-induced CXCL2
      upregulation in the rat spiral ligament fibrocytes. Two AP-1 motifs in the 5'
      flanking region of CXCL2 appeared to function as a nontypeable H. influenzae
      responsive element, and the proximal AP-1 motif was found to have a higher
      binding affinity to nontypeable H. influenzae-activated c-Jun than that of the
      distal one. Our results will enable us better to understand the molecular
      pathogenesis of middle ear infection-induced inner ear inflammation.

PMID- 22379038
TI  - CD31: beyond a marker for endothelial cells.

PMID- 22379037
TI  - Intrinsic differences in the initiation of B cell receptor signaling favor
      responses of human IgG(+) memory B cells over IgM(+) naive B cells.
AB  - The acquisition of long-lived memory B cells (MBCs) is critical for the defense
      against many infectious diseases. Despite their importance, little is known about
      how Ags trigger human MBCs, even though our understanding of the molecular basis
      of Ag activation of B cells in model systems has advanced considerably. In this
      study, we use quantitative, high-resolution, live-cell imaging at the single-cell
      and single-molecule levels to describe the earliest Ag-driven events in human
      isotype-switched, IgG-expressing MBCs and compare them with those in IgM
      expressing naive B cells. We show that human MBCs are more robust than naive B
      cells at each step in the initiation of BCR signaling, including interrogation of
      Ag-containing membranes, formation of submicroscopic BCR oligomers, and
      recruitment and activation of signaling-associated kinases. Despite their robust
      response to Ag, MBCs remain highly sensitive to FcgammaRIIB-mediated inhibition.
      We also demonstrate that in the absence of Ag, a portion of MBC receptors
      spontaneously oligomerized, and phosphorylated kinases accumulated at the
      membrane and speculate that heightened constitutive signaling may play a role in
      maintaining MBC longevity. Using high-resolution imaging, we have provided a
      description of the earliest events in the Ag activation of MBCs and evidence for
      acquired cell-intrinsic differences in the initiation of BCR signaling in human
      naive and MBCs.

PMID- 22379039
TI  - What's going on at age 11: development of the European Journal of Cardiovascular
      Nursing.

PMID- 22379040
TI  - Exercise programmes and quality of life in the elderly: important facts.

PMID- 22379042
TI  - Antigenic relationships between Bovine viral diarrhea virus 1 and 2 and HoBi
      virus: possible impacts on diagnosis and control.
AB  - The emergence of a newly recognized group of pestiviruses in cattle, the HoBi
      like viruses, requires an evaluation of the available diagnostic tools and
      vaccines. The present study compared antigenic characteristics of Bovine viral
      diarrhea virus 1 and 2 (BVDV-1, -2) strains and HoBi virus. This comparison was
      based on detection of HoBi virus and antibodies against it by commercial enzyme
      linked immunosorbent assays (ELISAs) and the level of cross-neutralizing
      antibodies present in sera from animals vaccinated with BVDV. Reactivity with a
      panel of monoclonal antibodies (mAbs) revealed greater cross-reactivity between
      BVDV species (BVDV-1, -2) and HoBi epitopes within E(rns) and NS2/3 proteins than
      between epitopes located in the E2 glycoprotein. The results suggest that a
      diagnostic test designed to detect both BVDV species and HoBi could be based on
      E(rns) or NS2/3 epitopes, while variation among E2 epitopes could be exploited in
      tests for differentiation of pestivirus species. The threshold of detection of
      HoBi virus by an antigen-capture ELISA kit based on detection of E(rns) was
      statistically similar to that for BVDV. In contrast, 2 commercial ELISA kits
      designed to detect antibodies against BVDV missed 22.2% and 77.7%, respectively,
      of serum samples harboring HoBi virus-neutralizing antibodies. In addition, sera
      of calves vaccinated with BVDV-1 and -2 presented low neutralizing activity
      against HoBi virus. The results demonstrate that in spite of antigenic
      similarities, HoBi virus is antigenically distinct from both BVDV species.
      Detection and control of HoBi virus infections in cattle would thus require the
      development of new diagnostic reagents and reformulation of current vaccines.

PMID- 22379043
TI  - Detection of Porcine reproductive and respiratory syndrome virus (PRRSV)
      antibodies in oral fluid specimens using a commercial PRRSV serum antibody enzyme
      linked immunosorbent assay.
AB  - The purpose of the present study was to evaluate the diagnostic performance of a
      commercial serum antibody enzyme-linked immunosorbent assay (ELISA) modified to
      detect anti-Porcine reproductive and respiratory syndrome virus (PRRSV)
      antibodies in pen-based oral fluid specimens. Experimental and field oral fluid
      samples of defined status in reference to exposure of swine with PRRSV were used
      to derive the kinetics of detectable concentrations of antibody against PRRSV.
      Immunoglobulin (Ig)M and IgA were readily detected in oral fluid specimens from
      populations in which PRRSV infection was synchronized among all individuals but
      not in samples collected in commecial herds. In contrast, IgG was readily
      detected at diagnostically useful levels in both experimental and field samples
      for up to 126 days. Estimates of the IgG oral fluid ELISA performance were based
      on results from testing positive oral fluid samples (n = 492) from experimentally
      inoculated pigs (n = 251) and field samples (n = 241) and negative oral fluid
      samples (n = 367) from experimentally inoculated pigs (n = 84) and field samples
      (n = 283). Receiver operating characteristic analysis estimated the diagnostic
      sensitivity and specificity of the assay as 94.7% (95% confidence interval [CI]:
      92.4, 96.5) and 100% (95% CI: 99.0, 100.0), respectively, at a sample-to-positive
      ratio cutoff of >=0.40. The results of the study suggest that the IgG oral fluid
      ELISA can provide efficient, cost-effective PRRSV monitoring in commercial herds
      and PRRSV surveillance in elimination programs.

PMID- 22379044
TI  - Application of the Ceditest(r) FMDV type O and FMDV-NS enzyme-linked
      immunosorbent assays for detection of antibodies against Foot-and-mouth disease
      virus in selected livestock and wildlife species in Uganda.
AB  - Diagnosis and control of Foot-and-mouth disease virus (FMDV) requires rapid and
      sensitive diagnostic tests. Two antibody enzyme-linked immunosorbent assay
      (ELISA) kits, Ceditest(r) FMDV-NS for the detection of antibodies against the
      nonstructural proteins of all FMDV serotypes and Ceditest(r) FMDV type O for the
      detection of antibodies against serotype O, were evaluated under African endemic
      conditions where the presence of multiple serotypes and the use of nonpurified
      vaccines complicate serological diagnosis. Serum samples from 218 African
      buffalo, 758 cattle, 304 goats, and 88 sheep were tested using both kits, and
      selected samples were tested not only in serotype-specific ELISAs for antibodies
      against primarily FMDV serotype O, but also against other serotypes. The FMDV-NS
      assay detected far more positive samples (93%) than the FMDV type O assay (30%)
      in buffalo (P < 0.05), with predominant antibodies against the South African
      Territories (SAT) serotypes, while the seroprevalence was generally comparable in
      cattle with antibodies against serotype O elicited by infection and/or
      vaccination. However, some districts had higher seroprevalence using the FMDV
      type O assay indicating vaccination without infection, while 1 cattle herd with
      antibodies against the SAT serotypes had far more positive samples (85%) using
      the FMDV-NS versus the FMDV type O (10%), consistent with the latter test's lower
      sensitivity for antibodies against SAT serotypes. Based on the current
      investigation, the FMDV type O ELISA may be limited by the presence of SAT
      serotypes. The FMD NS assay worked well as a screening test for antibodies
      against all FMDV serotypes present in Uganda; however, as long as nonpurified
      vaccines are applied in the region, this test cannot be used to differentiate
      between vaccinated and infected animals.

PMID- 22379045
TI  - Interference in diagnostic tests for brucellosis in cattle recently vaccinated
      against leptospirosis.
AB  - The aim of the current study was to verify if cattle vaccinated against
      leptospirosis may react in diagnostic tests for brucellosis. Sixty cows were
      divided into 5 groups, each comprising 12 animals. Four groups were given
      different vaccines against leptospirosis, while the control group received only
      saline. Two doses of vaccine were given, as recommended by the manufacturers.
      Serum samples were collected on the first day of immunization (day 0) and on
      postvaccination days 7, 14, 21, 28, 35, 42, 49, 56, 96, and 126. All the serum
      samples were tested for brucellosis and leptospirosis. Twenty animals were
      reactive at least once to the Rose Bengal test, but by day 96, no further
      reactions were elicited by this test. Twenty-six samples were reactive to the
      Rose Bengal test, but only 7 remained positive in confirmatory tests: 1 to the 2
      mercaptoethanol test, 2 to the fluorescence polarization assay, and 6 to indirect
      enzyme-linked immunosorbent assays. None of the samples was reactive in the
      complement fixation test. None of the animals in the control group was reactive.
      A significant difference was found between the control group and the groups
      vaccinated against leptospirosis, according to Fisher exact test. However, the
      groups were found to respond independently of the vaccine brand. The results
      indicate that cattle vaccinated against leptospirosis may show reactivity on
      screening tests for brucellosis.

PMID- 22379046
TI  - Validation and application of multi-residue analysis of eight anticoagulant
      rodenticides by high-performance liquid chromatography with fluorimetric
      detection.
AB  - Poisoning of domestic animals is frequently caused by anticoagulant rodenticides.
      Validation and applications of a rapid and reliable method for the simultaneous
      determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum,
      coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin) in
      baits and animal livers using high-performance liquid chromatography with
      fluorescence detection are reported herein. The methodology was validated by an
      in-house validation model at 2.5 mg/kg, which is the level commonly found in the
      tissues of poisoned domestic animals. The 8 anticoagulants can be determined at
      the concentration range of 1.25-100 mg/kg with determination coefficients higher
      than 0.992. A recovery value from 70% to 109% was observed for all the studied
      molecules. The results of the validation process demonstrate suitability for
      application in official analysis and for monitoring purposes of animal poisoning
      by anticoagulant rodenticides.

PMID- 22379047
TI  - Toxicokinetics and pathology of plant-associated acute selenium toxicosis in
      steers.
AB  - Sixteen of approximately 500 yearling steers died of acute selenium (Se)
      toxicosis after grazing on a Se-contaminated range for only a few days. Field
      studies and chemical analyses identified the predominant toxic plant as western
      aster (Symphyotrichum ascendens, previously Aster ascendens), which contained
      over 4,000 ppm Se (dry weight). Several dead animals that were necropsied had
      acute severe myocardial necrosis characterized by edema and myocyte swelling,
      with hypereosinophilia, clumping, and coagulation of myocardial proteins. Whole
      blood from 36 surviving steers was collected and analyzed, and 10 steers with
      elevated Se concentrations were selected for close monitoring and clinical
      evaluations. Each steer was weighed, and serum, blood, liver, skeletal muscle,
      and hair were regularly collected after removal from the Se-contaminated range.
      One animal that died 18 days after exposure was necropsied and exhibited severe
      multifocal myocardial fibrosis with extensive hepatic congestion, degeneration,
      and hemosiderosis. At 180 days postexposure, 2 of the 10 steers were euthanized,
      and tissue samples were collected. Both steers had rare, small fibrotic foci in
      their hearts. The Se elimination half-lives from serum, whole blood, liver, and
      muscle of the recovering steers were 40.5 +/- 8.2, 115.6 +/- 25.1, 38.2 +/- 5.0,
      and 98.5 +/- 19.1 days, respectively. The Se concentration in hair reached a peak
      of 11.5 +/- 5.3 ppm at 22 days postexposure. The findings indicate that cattle
      are sensitive to acute Se toxicosis caused by ingestion of Se-accumulator plants,
      with myocardial necrosis as the primary lesion. Some poisoned animals may develop
      congestive heart failure weeks after the toxic exposure, and in the current
      study, Se was slowly excreted requiring a relatively long withdrawal time.

PMID- 22379048
TI  - Diagnostic sensitivity and specificity of in situ hybridization and
      immunohistochemistry for Eastern equine encephalitis virus and West Nile virus in
      formalin-fixed, paraffin-embedded brain tissue of horses.
AB  - Immunohistochemistry (IHC) and in situ hybridization (ISH) can be used either to
      detect or to differentiate between Eastern equine encephalitis virus (EEEV) and
      West Nile virus (WNV) within formalin-fixed, paraffin-embedded (FFPE) brain
      tissue of horses. To compare the diagnostic sensitivity and specificity of ISH
      and IHC, FFPE brain tissue from 20 EEEV-positive horses and 16 WNV-positive
      horses were tested with both EEEV and WNV oligoprobes and EEEV- and WNV-specific
      antibodies. Reverse transcription polymerase chain reaction (RT-PCR) for
      detection of EEEV and WNV was used as the gold standard to confirm infection. All
      horses that tested positive for EEEV by RT-PCR also tested positive by IHC and
      ISH, except for 1 case that was false-negative by ISH. In contrast, all horses
      that tested positive for WNV by RT-PCR tested negative by IHC and only 2 horses
      tested positive by ISH. No false-positives were detected with either method for
      both viruses. Both IHC and ISH are highly specific and sensitive diagnostic
      methods to detect EEEV in equine FFPE brain tissues, although neither appear
      effective for the diagnosis of WNV in equine neurologic cases.

PMID- 22379049
TI  - Detection of a putative hemolysin operon, hhdBA, of Haemophilus parasuis from
      pigs with Glasser disease.
AB  - The aim of the current study was to investigate whether polymerase chain reaction
      amplification of 16S ribosomal (r)RNA and a putative hemolysin gene operon,
      hhdBA, can be used to monitor live pigs for the presence of Haemophilus parasuis
      and predict the virulence of the strains present. Nasal cavity swabs were taken
      from 30 live, healthy, 1- to 8-week-old pigs on a weekly cycle from a commercial
      Thai nursery pig herd. A total of 27 of these pigs (90%) tested positive for H.
      parasuis as early as week 1 of age. None of the H. parasuis-positive samples from
      healthy pigs was positive for the hhdBA genes. At the same pig nursery, swab
      samples from nasal cavity, tonsil, trachea, and lung, and exudate samples from
      pleural/peritoneal cavity were taken from 30 dead pigs displaying typical
      pathological lesions consistent with Glasser disease. Twenty-two of 140 samples
      (15.7%) taken from 30 diseased pigs yielded a positive result for H. parasuis.
      Samples from the exudate (27%) yielded the most positive results, followed by
      lung, tracheal swab, tonsil, and nasal swab, respectively. Out of 22 positive
      samples, 12 samples (54.5%) harbored hhdA and/or hhdB genes. Detection rates of
      hhdA were higher than hhdB. None of the H. parasuis-positive samples taken from
      nasal cavity of diseased pigs tested positive for hhdBA genes. More work is
      required to determine if the detection of hhdBA genes is useful for identifying
      the virulence potential of H. parasuis field isolates.

PMID- 22379050
TI  - Comparison of two commercial enzyme-linked immunosorbent assays for the diagnosis
      of Porcine reproductive and respiratory syndrome virus infection.
AB  - Early diagnosis of Porcine reproductive and respiratory syndrome virus (PRRSV) is
      critically important for control of the disease. Two new commercially available
      enzyme-linked immunosorbent assays (ELISAs) based on different methodologies have
      been developed. In the present report, the 2 ELISAs were compared using blood
      samples from experimentally and naturally infected pigs. One of the 2 ELISAs was
      shown to be more sensitive than the other. The higher sensitivity of one of the
      ELISAs could pose a problem in PRRS diagnosis in endemic farms, because it can
      detect maternally derived antibodies for a longer time, overlapping with the
      detection of antibodies developed after PRRSV infection. However, the ELISA with
      higher sensitivity could be suitable for early detection of PRRSV antibodies in
      individual pigs, especially in PRRS-free herds.

PMID- 22379051
TI  - Emergence and pathogenicity of highly pathogenic Porcine reproductive and
      respiratory syndrome virus in Vientiane, Lao People's Democratic Republic.
AB  - Highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS)
      characterized by high fever, high morbidity, and high mortality in pigs of all
      ages emerged in China in 2006 and spread rapidly throughout Southeast Asia. In
      July 2010, a highly contagious swine disease with clinical signs similar to those
      of HP-PRRS was observed in the Lao People's Democratic Republic (Lao PDR). A
      field investigation covering 8 pig farms and 1 slaughterhouse in 7 different
      districts in the capital city of Vientiane was conducted to identify the disease.
      Total mortality rates ranged from 6.02% in boars to 91.28% in piglets (mean
      54.15%) across the farms investigated. Emergence of the HP-PRRS virus (HP-PRRSV)
      in Lao PDR was confirmed using real-time reverse transcription polymerase chain
      reaction as well as virus isolation and identification. An animal inoculation
      study was performed to characterize the HP-PRRSV responsible for this outbreak.
      Isolate Laos 1.13 was inoculated into 70-day-old specific pathogen-free pigs to
      study pathogenicity. Clinical signs of high fever, rubefaction, respiratory
      distress, nervous symptoms, and diarrhea were observed in inoculated pigs, as
      well as pathological hemorrhagic lesions consolidated in the lungs. Morbidity and
      mortality were 100% and 60%, respectively, in inoculated pigs. HP-PRRSV was re
      isolated from the inoculated pigs. Results suggested that the newly emerged HP
      PRRSV was responsible for recent outbreaks of the swine disease in Lao PDR. The
      current report highlights the importance of continuous surveillance in
      neighboring countries to prevent introduction of PRRS to new regions.

PMID- 22379052
TI  - Validation of an immunoperoxidase monolayer assay for total anti-Vaccinia virus
      antibody titration.
AB  - Vaccinia virus (VACV) has been associated with zoonotic exanthemic outbreaks
      affecting bovids and human beings, with significant public health and economic
      impacts. Rapid and reliable diagnostic methods are needed to detect and
      epidemiologically monitor antibodies to VACV. The current study describes the
      development of an immunoperoxidase monolayer assay (IPMA) for detection of total
      VACV antibodies in bovine serum. The assay was validated by comparison with a
      plaque reduction neutralization test (PRNT). Kappa index of agreement, diagnostic
      sensitivity, specificity, and accuracy of the IPMA were -1.008, 100%, 96%, and
      98%, respectively, when compared with PRNT on 148 field bovine sera.
      Repeatability tests on 32 field-positive serum samples revealed that intraclass
      coefficient correlation was 0.86. In experimentally infected cattle, VACV
      antibodies were detectable by IPMA 4 days postinfection, which was more than 2
      weeks earlier than with the PRNT, indicating that IPMA could be a more sensitive
      test than the latter. In 4 naturally VACV-diseased cows monitored for 13 months,
      IPMA could detect VACV antibodies up to 13 months, a longer time than PRNT. The
      IPMA is simpler to produce and perform when compared with PRNT and is time saving
      and suitable for large-scale surveys of VACV infection in bovine.

PMID- 22379053
TI  - Identification of a novel adenovirus in a cotton-top tamarin (Saguinus oedipus).
AB  - A novel adenovirus was identified in a cotton-top tamarin (Saguinus oedipus) with
      diarrhea by negative-staining electron microscopy of feces, consensus polymerase
      chain reaction, and sequencing. Partial sequences were obtained from the DNA
      dependent DNA polymerase, the p52k gene, and the hexon. Bayesian and maximum
      likelihood phylogenetic analyses indicated that the virus is a member of the
      genus Mastadenovirus, and is herein termed Saguinus siadenovirus 1. The phylogeny
      of the mastadenoviruses is similar to that of their hosts, supporting
      coevolution. Support for this was strongest in the analysis of the predicted
      hexon protein. The obtained sequences were GC-rich, which may suggest a lack of
      recent host jumps. The diversity and evolution of the adenoviruses of platyrrhine
      primates merits further investigation. Additional study of the association of
      this virus with diarrhea is indicated.

PMID- 22379054
TI  - Comparative evaluation of specific methods for labeling of Encephalitozoon
      cuniculi in paraffin wax-embedded tissue samples.
AB  - Detection of the microsporidian Encephalitozoon cuniculi in tissue samples is
      considered difficult. The aim of the current study was to determine whether
      immunohistochemistry (IHC) and in situ hybridization (ISH) represent reliable
      methods for the detection of E. cuniculi in postmortem tissue samples of rabbits.
      Paraffin-embedded tissue sections of brain and kidneys of 48 naturally infected
      pet rabbits, 10 negative controls, and the eyes of 3 further rabbits were used
      for all investigations. By IHC in 19 animals (37.3%), spores could be clearly
      detected and were all equally stained. By ISH using a digoxigenin-labeled
      oligonucleotide probe, only 6 animals (11.8%) proved undoubtedly positive. In
      these cases, many parasite-like objects revealed strong typical purple-black
      positive signals. However, several of the examined samples showed only partial
      staining of the pathogen or unclear results. Thus, in order to find an
      explanation for these inconsistent ISH results and to take a more detailed look
      at the different developmental stages of the organism, electron microscopy was
      applied. Empty spores, which had already discharged their polar filaments,
      prevailed in total number. Taken together, both techniques are rather
      insensitive, but under the condition that sufficient numbers of microsporidia are
      present, IHC can be recommended for specific identification of E. cuniculi in
      tissue samples. In contrast, ISH failed to detect some developmental stages of
      the organism, and, as such, ISH is therefore considered an inappropriate
      diagnostic method.

PMID- 22379055
TI  - Longitudinal assessment of two Mycoplasma hyopneumoniae enzyme-linked
      immunosorbent assays in challenged and contact-exposed pigs.
AB  - The objective of the current study was to compare the sensitivity of 2 Mycoplasma
      hyopneumoniae enzyme-linked immunosorbent assays (ELISAs) in experimentally
      challenged and contact-exposed pigs in a long-term longitudinal assessment. On
      day 0 of the assessment, twelve 2-month-old M. hyopneumoniae-negative pigs were
      inoculated with M. hyopneumoniae strain 232 (group A). Twelve negative pigs were
      placed alongside the inoculated pigs, allowing direct contact exposure (group B).
      A third group of 12 pigs was allocated into 2 independent pens; no direct contact
      was allowed (group C). A longitudinal serologic profile was performed; samples
      were collected on days 0, 28, 35, 42, 49, 63, 91, 119, 154, and 170 of the study.
      Serum samples were tested using a blocking ELISA and an indirect ELISA. Results
      of the study demonstrated higher sensitivity of the blocking ELISA during early
      infection (clinical signs). Both ELISAs were 100% sensitive in challenged and
      naturally infected groups at several testing points during late infection (63,
      91, 119, 154, and 170 days of the study) and showed a long antibody detection
      period. Both tests worked equally well during the chronic phase of infection but
      the blocking ELISA was more sensitive during acute stages of infection.

PMID- 22379056
TI  - Fatal Caprine arthritis encephalitis virus-like infection in 4 Rocky Mountain
      goats (Oreamnos americanus).
AB  - Over a 3.5-year period, 4 Rocky Mountain goats (Oreamnos americanus), housed at a
      single facility, developed clinical disease attributed to infection by Caprine
      arthritis encephalitis virus (CAEV). Ages ranged from 1 to 10 years. Three of the
      goats, a 1-year-old female, a 2-year-old male, and a 5-year-old male, had been
      fed raw domestic goat milk from a single source that was later found to have CAEV
      on the premises. The fourth animal, a 10-year-old male, had not ingested domestic
      goat milk but had been housed with the other 3 Rocky Mountain goats. All 4
      animals had clinical signs of pneumonia prior to death. At necropsy, findings in
      lungs included marked diffuse interstitial pneumonia characterized histologically
      by severe lymphoplasmacytic infiltrates with massive alveolar proteinosis,
      interstitial fibrosis, and type II pneumocyte hyperplasia. One animal also
      developed left-sided hemiparesis, and locally extensive lymphoplasmacytic
      myeloencephalitis was present in the cranial cervical spinal cord. Two animals
      had joint effusions, as well as severe lymphoplasmacytic and ulcerative
      synovitis. Immunohistochemical staining of fixed sections of lung tissue from all
      4 goats, as well as spinal cord in 1 affected animal, and synovium from 2
      affected animals were positive for CAEV antigen. Serology testing for anti-CAEV
      antibodies was positive in the 2 goats tested. The cases suggest that Rocky
      Mountain goats are susceptible to naturally occurring CAEV infection, that CAEV
      from domestic goats can be transmitted to this species through infected milk and
      by horizontal transmission, and that viral infection can result in clinically
      severe multisystemic disease.

PMID- 22379057
TI  - Acute bovine viral diarrhea associated with extensive mucosal lesions, high
      morbidity, and mortality in a commercial feedlot.
AB  - In 2008, a northwest Texas feedlot underwent an outbreak of Bovine viral diarrhea
      virus (BVDV) causing high morbidity and mortality involving 2 lots of calves
      (lots A and B). Severe mucosal surface lesions were observed grossly in the oral
      cavity, larynx, and esophagus. Mucosal lesions varied from small (1-3 mm)
      infrequent mucosal ulcerations to large (5 mm to 1 cm) and coalescing
      ulcerations. Necrotic debris was present in ulcerations of some mortalities with
      some having plaque-like debris, but other mortalities presented more
      proliferative lesions. A calf persistently infected with BVDV arrived with one
      lot and the isolated virus was genotyped as BVDV-1b. Identical BVDV-1b strains
      were isolated from 2 other mortalities. A BVDV-2a genotype was also isolated in
      this outbreak. This genotype was identical to all BVDV-2a strains isolated in
      both lots. Serum samples were collected from exposed and unexposed animals and
      tested for antibodies for multiple viral pathogens. Seropositivity ranged from
      zero percent for calicivirus to 100% positive to Pseudocowpox virusx. At the end
      of the feeding period, the morbidity and mortality for the 2 lots involved was
      76.2% and 30.8%, respectively, for lot A, and 49.0% and 5.6%, respectively, for
      lot B. Differential diagnoses included vesicular stomatitis viruses, Bovine
      papular stomatitis virus, and Foot-and-mouth disease virus. Based on the present
      case, acute BVDV should be considered when mucosal lesions are observed grossly.

PMID- 22379058
TI  - Uterine heterologous malignant mixed Mullerian tumor in a dwarf rabbit
      (Oryctolagus cuniculus).
AB  - Malignant mixed Mullerian tumor (MMMT) is a rare neoplasm of the female genital
      system. A case of MMMT in the uterus of an 8-year-old female dwarf rabbit, which
      died with clinical signs associated with severe acute dyspnea and anorexia, is
      described. At necropsy, an oval, firm tumor was found in each of the 2 uterine
      horns. Numerous metastases were scattered throughout the mediastinum, thoracic
      diaphragm, and all pulmonary lobes. Microscopically, the tumors consisted of a
      poorly demarcated, unencapsulated neoplasm, composed of closely associated
      carcinomatous and sarcomatous components and areas of osteosarcomatous
      differentiation. Metastases were composed entirely of the sarcomatous component
      with osteosarcomatous differentiation. Immunohistochemically, the neoplastic
      epithelial component was positive for cytokeratin and negative for alpha-smooth
      muscle actin (alpha-SMA), vimentin, and desmin. The sarcomatous component was
      diffusely and strongly positive for vimentin, focally positive for alpha-SMA
      (<20% of cells positive), and negative for desmin. The neoplasm was diagnosed as
      a heterologous MMMT with metastases to the lung, mediastinum, and thoracic
      diaphragm.

PMID- 22379059
TI  - Enzootic calcinosis caused by Nierembergia rivularis in sheep.
AB  - Enzootic calcinosis was diagnosed in sheep in Uruguay in pastures containing the
      plant Nierembergia rivularis. In a flock of 200 sheep, 20 were affected and 12
      died. Clinical signs were anorexia, weight loss followed by cachexia, stiffness,
      and kyphosis. At necropsy and histologic examination, mineral deposits were
      observed on the medial layer of the arteries, heart, lungs, and kidneys. Similar
      lesions were also observed in 3 sheep forced to graze in an area containing the
      plant, while no lesions were observed in a control sheep that grazed in an area
      free of N. rivularis. It is concluded that N. rivularis is a calcinogenic plant
      for sheep.

PMID- 22379060
TI  - Confirmed case of encephalitis caused by Murray Valley encephalitis virus
      infection in a horse.
AB  - A 5-year-old Australian stock horse in Monto, Queensland, Australia, developed
      neurological signs and was euthanized after a 6-day course of illness.
      Histological examination of the brain and spinal cord revealed moderate to severe
      subacute, nonsuppurative encephalomyelitis. Sections of spinal cord stained
      positively in immunohistochemistry with a flavivirus-specific monoclonal
      antibody. Reverse transcription polymerase chain reaction assay targeting the
      envelope gene of flavivirus yielded positive results from brain, spinal cord,
      cerebrospinal fluid, and facial nerve. A flavivirus was isolated from the
      cerebrum and spinal cord. Nucleotide sequences obtained from amplicons from both
      tissues and virus isolated in cell culture were compared with those in GenBank
      and had 96-98% identity with Murray Valley encephalitis virus. The partial
      envelope gene sequence of the viral isolate clustered into genotype 1 and was
      most closely related to a previous Queensland isolate.

PMID- 22379061
TI  - Novel brain lesions caused by Edwardsiella tarda in a red tilapia (Oreochromis
      spp.).
AB  - The histological lesions caused by Edwardsiella tarda in a variety of fish
      species, including tilapia, have been well characterized. There are apparent
      differences in the type of inflammatory response manifested by these different
      species, which may be due to the fish species itself, the phase of infection, or
      the virulence factors produced by different strains of E. tarda. In catfish,
      systemic abscesses involving muscles of the flank or caudal peduncle are the most
      common lesions. By contrast, infection in tilapia and red sea bream is more
      likely to be associated with granulomatous inflammation. Necrotic meningitis,
      encephalitis, and vasculitis with fibrinoid necrosis of the blood vessels walls,
      as well as the formation of a plaque-like structure in the brain, are described
      in the current study. The presence of E. tarda was confirmed by microbiological
      isolation and a positive nested polymerase chain reaction in paraffin wax
      embedded tilapia tissues.

PMID- 22379062
TI  - Tick-borne encephalitis virus-neutralizing antibodies in different immunoglobulin
      preparations.
AB  - Patients with primary immunodeficiency (PIDs) depend on the presence of a variety
      of antibody specificities in intravenous immunoglobulin (IVIG). Using the tick
      borne encephalitis virus (TBEV), geographic variability in IVIG antibody content
      was shown. Care should therefore be exercised when treating PIDs in a given
      geography, as only locally sourced plasma contains the antibody specificities
      against the circulating pathogens in the given locality.

PMID- 22379063
TI  - Vaccination with a DNA vaccine coding for perforin-like protein 1 and MIC6
      induces significant protective immunity against Toxoplasma gondii.
AB  - Host cell invasion by Toxoplasma gondii is tightly related to microneme protein 6
      (MIC6) and T. gondii perforin-like protein 1 (TgPLP1). In this study, we
      constructed a DNA vaccine expressing a TgPLP1/MIC6 fusion protein using the
      pIRESneo vector, and we evaluated the immune response induced by this vaccine in
      Kunming mice. Levels of IgG antibody, gamma interferon (IFN-gamma), interleukin 2
      (IL-2), IL-12, IL-4, and IL-10 were examined. Five mice were chosen randomly from
      every group (vaccinated groups or the nonvaccinated control group) and were
      challenged intragastrically with 80 cysts of T. gondii strain PRU (genotype II)
      in order to observe mortality daily. To analyze protection against a less
      virulent challenge, eight mice of each group were orally infected with 20 cysts
      of strain PRU at the 14th day after the last immunization. The brain parasite
      load was evaluated 6 weeks after infection. The results demonstrated that
      immunization with pIRESneo/MIC6/PLP1 resulted in the lowest brain cyst count and
      prolonged the survival time of immunized mice. The levels of Toxoplasma-specific
      IgG, IFN-gamma, IL-2, and IL-12 increased significantly, and the numbers of cysts
      in brains decreased more obviously, in the group immunized with plasmid
      pIRESneo/MIC6/PLP1 than in the other groups (P < 0.05). Compared with
      pIRESneo/MIC6/PLP1, coimmunization with pIRESneo/MIC6/PLP1 and adjuvant murine IL
      18 promoted cellular and humoral immune responses but did not contribute
      significantly to cyst reduction (65.43% versus 61.60%) or the survival of
      immunized mice (45.0 +/- 2.9 days versus 42.8 +/- 2.9 days) (P > 0.05).
      Furthermore, the study also showed that the immune efficacy induced by
      pIRESneo/MIC6/PLP1 was better than that induced by pVAX/PLP1 or pVAX/MIC6 alone.

PMID- 22379064
TI  - Dexamethasone treatment has no effect on the formation of pneumococcal antibodies
      during community-acquired pneumonia.
AB  - In this study, the effect of dexamethasone on the formation of pneumococcal
      antibodies during community-acquired pneumonia (CAP) was investigated. No
      differences between CAP patients receiving dexamethasone as additional therapy
      and patients receiving a placebo were found with respect to immune response rates
      and mean baseline and convalescent-phase antibody concentrations.

PMID- 22379065
TI  - Performance of the QuantiFERON-cytomegalovirus (CMV) assay for detection and
      estimation of the magnitude and functionality of the CMV-specific gamma
      interferon-producing CD8(+) T-cell response in allogeneic stem cell transplant
      recipients.
AB  - The performance of the QuantiFERON-cytomegalovirus (CMV) assay was compared to
      that of a flow cytometry intracellular cytokine staining (ICS) method for the
      detection of CMV-specific gamma interferon (IFN-gamma)-producing CD8(+) T-cell
      responses in allogeneic stem cell transplant (allo-SCT) recipients and for
      estimations of their magnitude and functionality. A total of 90 whole-blood
      specimens from 23 allo-SCT recipients was analyzed by both methods. Overall, the
      percentage of specimens that yielded concordant results by both methods was 68.8%
      (kappa = 0.691; 95% confidence interval [CI], 0.548 to 0.835), and the
      sensitivity of the QuantiFERON-CMV assay for the detection of positive IFN-gamma
      T-cell responses (>0.2 IU/ml), taking the ICS method as the reference, was 76.3%.
      The magnitude of IFN-gamma-producing CD8(+) T-cell responses to CMV-specific
      peptides measured with the QuantiFERON-CMV assay correlated significantly (sigma
      = 0.695; P = <0.001) with that of the total IFN-gamma-producing CD8(+) T cells
      and dual-functional (IFN-gamma/tumor necrosis factor alpha [TNF-alpha] [sigma =
      0.652; P = <0.001] and IFN-gamma/CD107a [sigma = 0.690; P = <0.001]) and
      trifunctional (IFN-gamma/TNF-alpha/CD107a [sigma = 0.679; P = >0.001]) CMV
      specific CD8(+) T-cell responses, as quantitated by ICS. In summary, the data
      indicated that the QuantiFERON-CMV assay is less sensitive than the ICS method
      for the detection of CMV-specific IFN-gamma-producing CD8(+) T-cell responses in
      the allo-SCT setting. Nevertheless, it allowed the estimation of the total and
      polyfunctional CMV-specific IFN-gamma-producing CD8(+) T-cell responses in
      specimens that tested positive by both methods.

PMID- 22379066
TI  - Protection against lethal leptospirosis after vaccination with LipL32 coupled or
      coadministered with the B subunit of Escherichia coli heat-labile enterotoxin.
AB  - Leptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross
      protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface
      lipoprotein present in all pathogenic species of Leptospira, is a promising
      antigen candidate for a recombinant vaccine. However, several studies have
      reported a lack of protection when this protein is used as a subunit vaccine. In
      an attempt to enhance the immune response, we used LipL32 coupled to or
      coadministered with the B subunit of the Escherichia coli heat-labile enterotoxin
      (LTB) in a hamster model of leptospirosis. After homologous challenge with 5* the
      50% lethal dose (LD(50)) of Leptospira interrogans, animals vaccinated with
      LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival
      rates (P < 0.05) than animals from the control group. This is the first report of
      a protective immune response afforded by a subunit vaccine using LipL32 and
      represents an important contribution toward the development of improved
      leptospirosis vaccines.

PMID- 22379067
TI  - Comparison of the long-term immunogenicity of two pandemic influenza A/H1N1 2009
      vaccines, the MF59-adjuvanted and unadjuvanted vaccines, in adults.
AB  - Since the first reports of the A/H1N1 virus in April 2009, the pandemic influenza
      virus spread globally and circulated for a long time. The primary method for the
      control of influenza is vaccination, but levels of influenza vaccine-induced
      antibody are known to decline rapidly during a 6-month period. In adults aged 18
      to 64 years, we compared the long-term immunogenicity of two of the influenza
      A/H1N1 2009 monovalent vaccines, 3.75-MUg MF59-adjuvanted vaccine and 15-MUg
      unadjuvanted vaccine. The serum hemagglutinin inhibition (HI) titers were
      determined prevaccination and at 1, 6, and 10 months after vaccination. One
      hundred six (88.3%) of the 120 subjects were monitored for the entire 10-month
      period after receiving the influenza A/H1N1 2009 monovalent vaccine. There were
      60 patients who received the unadjuvanted vaccine and 46 patients who received
      the MF59-adjuvanted vaccine. The seroprotection rates, seroconversion rates, and
      the geometric mean titer (GMT) folds fulfilled the criteria of the European
      Medicines Agency (EMA) for influenza A/California/7/2009 (H1N1) at 1 month after
      vaccination irrespective of the vaccine composition. Although the GMTs at 1 month
      postvaccination were somewhat higher in the unadjuvanted vaccine recipients than
      in the MF59-adjuvanted vaccine recipients, the difference was not significant (P
      = 0.29). The seroprotection rates at 6 and 10 months postvaccination were
      preserved above 70% but only in the MF59-adjuvanted vaccine recipients. In
      conclusion, low-dose MF59-adjuvanted influenza vaccine, even with 3.75 MUg
      hemagglutinin antigen, might induce excellent long-term immunity that is
      comparable to the conventional dose of unadjuvanted vaccine among healthy adults
      aged 18 to 64 years.

PMID- 22379070
TI  - Sputum inflammatory phenotypes are not stable in children with asthma.
AB  - BACKGROUND: Two distinct, stable inflammatory phenotypes have been described in
      adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based
      on these phenotypes have been successful. This study evaluated sputum cytology in
      children with asthma to classify sputum inflammatory phenotypes and to assess
      their stability over time. METHODS: Sputum induction was performed in 51 children
      with severe asthma and 28 with mild to moderate asthma. Samples were classified
      as eosinophilic (>2.5% eosinophils), neutrophilic (>54% neutrophils); mixed
      granulocytic (>2.5% eosinophils, >54% neutrophils); or paucigranulocytic (<=2.5%
      eosinophils, <=54% neutrophils). Sputum induction was repeated every 3 months in
      children with severe asthma (n=42) over a 1-year period and twice in mild to
      moderate asthma (n=17) over 3-6 months. RESULTS: 62 children (78%) had raised
      levels of inflammatory cells in at least one sputum sample. In the longitudinal
      analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability
      in sputum inflammatory phenotype was observed in both the severe and the mild to
      moderate asthma groups. Change in phenotype was not related to change in inhaled
      corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in
      exhaled nitric oxide (FE(NO)). 24 children (41%) fulfilled the criteria for non
      eosinophilic asthma on one occasion and eosinophilic on another. There were no
      differences in severity, asthma control, atopy, ICS dose or forced expiratory
      volume in 1 s between those who were always non-eosinophilic and those always
      eosinophilic. CONCLUSION: Raised levels of inflammatory cells were frequently
      found in children with asthma of all severities. Sputum inflammatory phenotype
      was not stable in children with asthma.

PMID- 22379068
TI  - Prospective comparison of prognostic scores in palliative care cancer
      populations.
AB  - PURPOSE: Predicting prognosis in advanced cancer aids physicians in clinical
      decision making and can help patients and their families to prepare for the time
      ahead. MATERIALS AND METHODS: This multicenter, observational, prospective,
      nonrandomized population-based study evaluated life span prediction of four
      prognostic scores used in palliative care: the original palliative prognostic
      score (PaP Score), a variant of PaP Score including delirium (D-PaP Score), the
      Palliative Performance Scale, and the Palliative Prognostic Index. RESULTS: A
      total of 549 patients were enrolled onto the study. Median survival of the entire
      group was 22 days (95% confidence intervals [95% CI] = 19-24). All four
      prognostic models discriminated well between groups of patients with different
      survival probabilities. Log-rank tests were all highly significant (p < .0001).
      The PaP and D-PaP scores were the most accurate, with a C index of 0.72 (95% CI =
      0.70-0.73) and 0.73 (95% CI = 0.71-0.74), respectively. CONCLUSION: It can be
      confirmed that all four prognostic scores used in palliative care studies
      accurately identify classes of patients with different survival probabilities.
      The PaP Score has been extensively validated and shows high accuracy and
      reproducibility in different settings.

PMID- 22379071
TI  - Early antibiotic treatment for Pseudomonas aeruginosa eradication in patients
      with cystic fibrosis: a randomised multicentre study comparing two different
      protocols.
AB  - BACKGROUND: Pseudomonas aeruginosa chronic pulmonary infection is an unfavourable
      event in cystic fibrosis. Bacterial clearance is possible with an early
      antibiotic treatment upon pathogen isolation. Currently, no best practice exists
      for early treatment. The efficacy of two different regimens against initial P.
      aeruginosa infection was assessed. METHODS: In a randomised, open-label, parallel
      group study involving 13 centres, the superiority of inhaled tobramycin/oral
      ciprofloxacin compared with inhaled colistin/oral ciprofloxacin (reference
      treatment) over 28 days was evaluated. Patients were eligible if they were older
      than 1 year with first or new P. aeruginosa isolation. Treatments were assigned
      equally by centralised balanced randomisation, stratified by age and forced
      expiratory volume in 1 s values. The participants and those giving the
      intervention were not masked to arm assignments. The primary endpoint was P.
      aeruginosa eradication, defined as three successive negative cultures in 6
      months. Analysis was by intention to treat. This trial was registered with
      EudraCT, number 2008-006502-42. RESULTS: 105 patients were assigned to inhaled
      colistin/oral ciprofloxacin (arm A) and 118 to inhaled tobramycin/oral
      ciprofloxacin (arm B). All patients were analysed. P. aeruginosa was eradicated
      in 66 (62.8%) patients in arm A and in 77 (65.2%) in arm B (OR 0.90, 95% CI 0.52
      to 1.55, p=0.81). Following treatment, an increase in Stenotrophomonas
      maltophilia was noted (OR 3.97, 95% CI 2.27 to 6.94, p=0.001) with no differences
      between the two arms (OR 0.89, 95% CI 0.44 to 1.78, p=0.88). CONCLUSIONS: No
      superiority of treatment under study was demonstrated in comparison to the
      reference treatment. Early eradication treatment was associated with an increase
      in S maltophilia.

PMID- 22379072
TI  - Adipose tissue inflammation and adiponectin resistance in patients with advanced
      heart failure: correction after ventricular assist device implantation.
AB  - BACKGROUND: Heart failure (HF) is characterized by inflammation, insulin
      resistance, and progressive catabolism. We hypothesized that patients with
      advanced HF also develop adipose tissue inflammation associated with impaired
      adipokine signaling and that hemodynamic correction through implantation of
      ventricular assist devices (VADs) would reverse adipocyte activation and correct
      adipokine signaling in advanced HF. METHODS AND RESULTS: Circulating insulin,
      adiponectin, leptin, and resistin levels were measured in 36 patients with
      advanced HF before and after VAD implantation and 10 healthy control subjects.
      Serum adiponectin was higher in HF patients before VAD implantation compared with
      control subjects (13.3+/-4.9 versus 6.4+/-2.1 MUg/mL, P=0.02). VAD implantation
      (mean, 129+/-99 days) reduced serum adiponectin (7.4+/-3.4 MUg/mL, P<0.05) and
      improved insulin resistance (Homeostasis Assessment Model of insulin resistance:
      7.6+/-7.7-4.5+/-3.6; P=0.012). [corrected] Adiponectin expression in adipose
      tissue decreased after VAD implantation (-65%; P<0.03). Adiponectin receptor
      expression was suppressed in the failing myocardium compared with control
      subjects and increased after mechanical unloading. Histomorphometric analysis of
      adipose tissue specimens revealed reduced adipocyte size in patients with
      advanced HF compared with control subjects (2105+/-585 MUm(2) [corrected] versus
      5583+/-142 MUm(2) in control subjects; P<0.05), which increased after VAD
      placement. Of note, macrophage infiltration in adipose tissue was higher in
      advanced HF patients compared with control subjects (+25%; P<0.01), which
      normalized after VAD implantation. CONCLUSIONS: Adipose tissue inflammation and
      adiponectin resistance develop in advanced HF. Mechanical unloading of the
      failing myocardium reverses adipose tissue macrophage infiltration, inflammation,
      and adiponectin resistance in patients with advanced HF.

PMID- 22379073
TI  - Editorial: NKT get the 'flu: NKT cells as (mostly) good guys in influenza;
      monocytic cells as double agents.

PMID- 22379074
TI  - Editorial: Nyet to NETs? A pause for healthy skepticism.

PMID- 22379075
TI  - Carboxyl-terminal amino acids 1052 to 1082 of the latency-associated nuclear
      antigen (LANA) interact with RBP-Jkappa and are responsible for LANA-mediated RTA
      repression.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus
      8, is closely associated with several malignancies, including Kaposi's sarcoma,
      primary effusion lymphoma, and multicentric Castleman's disease. KSHV can
      establish lifelong latency in the host, but the mechanism is not fully
      understood. Previous studies have proposed a feedback model in which the viral
      replication and transcription activator (RTA) can induce the expression of the
      latency-associated nuclear antigen (LANA) during early infection. LANA, in turn,
      represses transcription and RTA function to establish and maintain KSHV latency.
      The interaction between LANA and the recombination signal sequence binding
      protein Jkappa (RBP-Jkappa, also called CSL), a major transcriptional repressor
      of the Notch signaling pathway, is essential for RTA repression. In the present
      study, we show that the LANA carboxyl-terminal amino acids 1052 to 1082 are
      responsible for the LANA interaction with RBP-Jkappa. The secondary structure of
      the LANA carboxyl terminus resembles the RBP-Jkappa-associated module (RAM) of
      Notch receptor. Furthermore, deletion of the region of LANA residues 1052 to 1082
      resulted in aberrant expression of RTA, leading to elevated viral lytic
      replication. For the first time, we dissected a conserved RBP-Jkappa binding
      domain in LANA and demonstrated that this domain was indispensable for LANA
      mediated repression of KSHV lytic genes, thus helping the virus maintain latency
      and control viral reactivation.

PMID- 22379076
TI  - In vitro epsilon RNA-dependent protein priming activity of human hepatitis B
      virus polymerase.
AB  - Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription
      of a pregenomic RNA (pgRNA) by using a multifunctional polymerase (HP). A
      critical function of HP is its specific recognition of a viral RNA signal termed
      epsilon (Hepsilon) located on pgRNA, which is required for specific packaging of
      pgRNA into viral nucleocapsids and initiation of viral reverse transcription. HP
      initiates reverse transcription by using itself as a protein primer (protein
      priming) and Hepsilon as the obligatory template. We have purified HP from human
      cells that retained Hepsilon binding activity in vitro. Furthermore, HP purified
      as a complex with Hepsilon, but not HP alone, displayed in vitro protein priming
      activity. While the HP-Hepsilon interaction in vitro and in vivo required the
      Hepsilon internal bulge, but not its apical loop, and was not significantly
      affected by the cap-Hepsilon distance, protein priming required both the Hepsilon
      apical loop and internal bulge, as well as a short distance between the cap and
      Hepsilon, mirroring the requirements for RNA packaging. These studies have thus
      established new HBV protein priming and RNA binding assays that should greatly
      facilitate the dissection of the requirements and molecular mechanisms of HP
      Hepsilon interactions, RNA packaging, and protein priming.

PMID- 22379078
TI  - Acute and chronic T cell dynamics in the livers of simian immunodeficiency virus
      infected macaques.
AB  - The mucosal immune system, particularly the gastrointestinal tract, is critically
      involved in the pathogenesis of human immunodeficiency virus (HIV) infection.
      Since the liver drains most of the substances coming from the intestinal tract,
      it may also play a role in the pathogenesis of HIV infection. Here we examined
      the percentages and absolute numbers of T cell subsets in the liver in normal and
      simian immunodeficiency virus (SIV)-infected macaques. Most of the T cells in the
      liver were CD8(+) memory cells, and most of these had an effector memory (CD95(+)
      CD28(-)) phenotype. CD4(+) T cells constituted approximately 20% of the liver T
      cell population, but the vast majority of these were also memory (CD95(+))
      CCR5(+) cells, suggesting they were potential targets for viral infection. After
      SIV infection, CD4(+) T cells were markedly reduced, and increased proliferation
      and absolute numbers of CD8(+) T cells were detected in the liver. These data
      suggest that the liver is a major source of antigenic stimulation for promoting
      CD8(+) T cells and possibly a source for early CD4(+) T cell infection and
      destruction.

PMID- 22379077
TI  - Decreased neuraminidase activity is important for the adaptation of H5N1
      influenza virus to human airway epithelium.
AB  - Highly pathogenic avian H5N1 influenza viruses remain a pandemic threat.
      Antiviral drugs such as neuraminidase (NA) inhibitors will be crucial for disease
      control in the event of a pandemic. Should drug-resistant H5N1 viruses develop,
      all defense strategies will be compromised. To determine the likelihood and
      mechanisms of emergence of NA inhibitor-resistant H5N1 variants in humans, we
      serially passaged two H5N1 viruses, A/Hong Kong/213/03 and A/Turkey/65-1242/06,
      in normal human bronchial epithelial (NHBE) cells in the presence of oseltamivir,
      zanamivir, or peramivir. To monitor the emergence of changes associated with the
      adaptation of H5N1 viruses to humans, we passaged the strains in the absence of
      drugs. Under pressure of each NA inhibitor, A/Turkey/65-1242/06 developed
      mutations in the hemagglutinin (HA) (H28R and P194L/T215I) and NA (E119A)
      proteins that reduced virus binding to alpha2,3-sialyl receptor and NA activity.
      Oseltamivir pressure selected a variant of A/Hong Kong/213/03 virus with HA P194S
      mutation that decreased viral binding to alpha2,6 receptor. Under peramivir
      pressure, A/Hong Kong/213/03 virus developed a novel NA mutation, R156K, that
      reduced binding to all three drugs, caused about 90% loss of NA activity, and
      compromised replication in NHBE cells. Both strains were eliminated in NHBE cells
      when they were cultivated in the absence of drugs. Here, we show for the first
      time that decreased NA activity mediated through NA inhibitors is essential for
      the adaptation of pandemic H5N1 influenza virus to humans. This ability of
      decreased NA activity to promote H5N1 infection underlines the necessity to
      optimize management strategies for a plausible H5N1 pandemic.

PMID- 22379079
TI  - Bacteriophage phi6 nucleocapsid surface protein 8 interacts with virus-specific
      membrane vesicles containing major envelope protein 9.
AB  - Enveloped double-stranded RNA (dsRNA) bacterial virus Pseudomonas phage phi6 has
      been developed into an advanced assembly system where purified virion proteins
      and genome segments self-assemble into infectious viral particles, inferring the
      assembly pathway. The most intriguing step is the membrane assembly occurring
      inside the bacterial cell. Here, we demonstrate that the middle virion shell,
      made of protein 8, associates with the expanded viral core particle and the virus
      specific membrane vesicle.

PMID- 22379080
TI  - Helper virus-independent transcription and multimerization of a satellite RNA
      associated with cucumber mosaic virus.
AB  - Satellite RNAs are the smallest infectious agents whose replication is thought to
      be completely dependent on their helper virus (HV). Here we report that, when
      expressed autonomously in the absence of HV, a variant of satellite RNA (satRNA)
      associated with Cucumber mosaic virus strain Q (Q-satRNA) has a propensity to
      localize in the nucleus and be transcribed, generating genomic and antigenomic
      multimeric forms. The involvement of the nuclear phase of Q-satRNA was further
      confirmed by confocal microscopy employing in vivo RNA-tagging and double
      stranded-RNA-labeling assays. Sequence analyses revealed that the Q-satRNA
      multimers formed in the absence of HV, compared to when HV is present, are
      distinguished by the addition of a template-independent heptanucleotide motif at
      the monomer junctions within the multimers. Collectively, the involvement of a
      nuclear phase in the replication cycle of Q-satRNA not only provides a valid
      explanation for its persistent survival in the absence of HV but also suggests a
      possible evolutionary relationship to viroids that replicate in the nucleus.

PMID- 22379081
TI  - Protective role of interferon regulatory factor 3-mediated signaling against
      prion infection.
AB  - Abnormal prion protein (PrP(Sc)) generated from the cellular isoform of PrP
      (PrP(C)) is assumed to be the main or sole component of the pathogen, called
      prion, of transmissible spongiform encephalopathies (TSE). Because PrP is a host
      encoded protein, acquired immune responses are not induced in TSE. Meanwhile,
      activation of the innate immune system has been suggested to partially block the
      progression of TSE; however, the mechanism is not well understood. To further
      elucidate the role of the innate immune system in prion infection, we
      investigated the function of interferon regulatory factor 3 (IRF3), a key
      transcription factor of the MyD88-independent type I interferon (IFN) production
      pathway. We found that IRF3-deficient mice exhibited significantly earlier onset
      with three murine TSE strains, namely, 22L, FK-1, and murine bovine spongiform
      encephalopathy (mBSE), following intraperitoneal transmission, than with wild
      type controls. Moreover, overexpression of IRF3 attenuated prion infection in the
      cell culture system, while PrP(Sc) was increased in prion-infected cells treated
      with small interfering RNAs (siRNAs) against IRF3, suggesting that IRF3
      negatively regulates PrP(Sc) formation. Our findings provide new insight into the
      role of the host innate immune system in the pathogenesis of prion diseases.

PMID- 22379082
TI  - Preclinical evaluation of a genetically engineered herpes simplex virus
      expressing interleukin-12.
AB  - Herpes simplex virus 1 (HSV-1) mutants that lack the gamma(1)34.5 gene are unable
      to replicate in the central nervous system but maintain replication competence in
      dividing cell populations, such as those found in brain tumors. We have
      previously demonstrated that a gamma(1)34.5-deleted HSV-1 expressing murine
      interleukin-12 (IL-12; M002) prolonged survival of immunocompetent mice in
      intracranial models of brain tumors. We hypothesized that M002 would be suitable
      for use in clinical trials for patients with malignant glioma. To test this
      hypothesis, we (i) compared the efficacy of M002 to three other HSV-1 mutants,
      R3659, R8306, and G207, in murine models of brain tumors, (ii) examined the
      safety and biodistribution of M002 in the HSV-1-sensitive primate Aotus nancymae
      following intracerebral inoculation, and (iii) determined whether murine IL-12
      produced by M002 was capable of activating primate lymphocytes. Results are
      summarized as follows: (i) M002 demonstrated superior antitumor activity in two
      different murine brain tumor models compared to three other genetically
      engineered HSV-1 mutants; (ii) no significant clinical or magnetic resonance
      imaging evidence of toxicity was observed following direct inoculation of M002
      into the right frontal lobes of A. nancymae; (iii) there was no histopathologic
      evidence of disease in A. nancymae 1 month or 5.5 years following direct
      inoculation; and (iv) murine IL-12 produced by M002 activates A. nancymae
      lymphocytes in vitro. We conclude that the safety and preclinical efficacy of
      M002 warrants the advancement of a Deltagamma(1)34.5 virus expressing IL-12 to
      phase I clinical trials for patients with recurrent malignant glioma.

PMID- 22379083
TI  - UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human
      immunodeficiency virus type 1 subtype C.
AB  - Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by
      the virion surface envelope (Env) glycoproteins, making it a desirable target for
      antiretroviral entry inhibitors. We previously isolated a family of gp120 binding
      RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this
      study, we assessed the activity of a shortened synthetic derivative of the B40
      aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1
      tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of
      the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar
      range. The aptamer had little toxicity in tests with cell lines and primary
      cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may
      be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed
      eight amino acid residues that modulated neutralization resistance. This included
      residues within the coreceptor binding site, at the base of the V3 loop, and in
      the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was
      also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and
      IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results
      suggest that UCLA1 may be suitable for development as a potent HIV-1 entry
      inhibitor.

PMID- 22379084
TI  - A role of template cleavage in reduced excision of chain-terminating nucleotides
      by human immunodeficiency virus type 1 reverse transcriptase containing the M184V
      mutation.
AB  - Resistance to nucleoside reverse transcriptase (RT) inhibitors is conferred on
      human immunodeficiency virus type 1 through thymidine analogue resistance
      mutations (TAMs) that increase the ability of RT to excise chain-terminating
      nucleotides after they have been incorporated. The RT mutation M184V is a potent
      suppressor of TAMs. In RT containing TAMs, the addition of M184V suppressed the
      excision of 3'-deoxy-3'-azidothymidine monophosphate (AZTMP) to a greater extent
      on an RNA template than on a DNA template with the same sequence. The
      catalytically inactive RNase H mutation E478Q abolished this difference. The
      reduction in excision activity was similar with either ATP or pyrophosphate as
      the acceptor substrate. Decreased excision of AZTMP was associated with increased
      cleavage of the RNA template at position -7 relative to the primer terminus,
      which led to increased primer-template dissociation. Whether M184V was present or
      not, RT did not initially bind at the -7 cleavage site. Cleavage at the initial
      site was followed by RT dissociation and rebinding at the -7 cleavage site, and
      the dissociation and rebinding were enhanced when the M184V mutation was present.
      In contrast to the effect of M184V, the K65R mutation suppressed the excision
      activity of RT to the same extent on either an RNA or a DNA template and did not
      alter the RNase H cleavage pattern. Based on these results, we propose that
      enhanced RNase H cleavage near the primer terminus plays a role in M184V
      suppression of AZT resistance, while K65R suppression occurs through a different
      mechanism.

PMID- 22379085
TI  - Differentiation-dependent changes in levels of C/EBPbeta repressors and
      activators regulate human papillomavirus type 31 late gene expression.
AB  - The liver-enriched transcriptional activator protein (LAP) isoform of
      CCAAT/enhancer binding protein beta (C/EBPbeta) is shown to be a major activator
      of differentiation-dependent human papillomavirus (HPV) late gene expression,
      while the liver-enriched inhibitory protein (LIP) isoform negatively regulates
      late expression. In undifferentiated cells, LIPs act as dominant-negative
      repressors of late expression, and upon differentiation, LIP levels are
      significantly reduced, allowing LAP-mediated activation of the late promoter.
      Importantly, knockdown of C/EBPbeta isoforms blocks activation of late gene
      expression from complete viral genomes upon differentiation.

PMID- 22379086
TI  - Widespread impact of HLA restriction on immune control and escape pathways of HIV
      1.
AB  - The promiscuous presentation of epitopes by similar HLA class I alleles holds
      promise for a universal T-cell-based HIV-1 vaccine. However, in some instances,
      cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical
      binding motifs are known to target epitopes at different frequencies, with
      different functional avidities and with different apparent clinical outcomes.
      Such differences may be illuminated by the association of similar HLA alleles
      with distinctive escape pathways. Using a novel computational method featuring
      phylogenetically corrected odds ratios, we systematically analyzed differential
      patterns of immune escape across all optimally defined epitopes in Gag, Pol, and
      Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301
      polymorphisms in 90 epitopes associated with HLA alleles belonging to shared
      supertypes. We detected differential escape in 37 of 38 epitopes restricted by
      more than one allele, which included 278 instances of differential escape at the
      polymorphism level. The majority (66 to 97%) of these resulted from the selection
      of unique HLA-specific polymorphisms rather than differential epitope targeting
      rates, as confirmed by gamma interferon (IFN-gamma) enzyme-linked immunosorbent
      spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral
      load were frequently observed between allele pairs that selected for differential
      escape. Furthermore, the total number of associated polymorphisms strongly
      correlated with average viral load. These studies confirm that differential
      escape is a widespread phenomenon and may be the norm when two alleles present
      the same epitope. Given the clinical correlates of immune escape, such
      heterogeneity suggests that certain epitopes will lead to discordant outcomes if
      applied universally in a vaccine.

PMID- 22379087
TI  - Genome-wide analysis of Epstein-Barr virus Rta DNA binding.
AB  - The Epstein-Barr virus (EBV) lytic transactivator Rta activates promoters through
      direct binding to cognate DNA sites termed Rta response elements (RREs). Rta also
      activates promoters that apparently lack Rta binding sites, notably Zp and Rp.
      Chromatin immunoprecipitation (ChIP) of endogenous Rta expressed during early
      replication in B95-8 cells was performed to identify Rta binding sites in the EBV
      genome. Quantitative PCR (qPCR) analysis showed strong enrichment for known RREs
      but little or no enrichment for Rp or Zp, suggesting that the Rta ChIP approach
      enriches for direct Rta binding sites. Rta ChIP combined with deep sequencing
      (ChIP-seq) identified most known RREs and several novel Rta binding sites. Rta
      ChIP-seq peaks were frequently upstream of Rta-responsive genes, indicating that
      these Rta binding sites are likely functioning as RREs. Unexpectedly, the BALF5
      promoter contained an Rta binding peak. To assess whether BALF5 might be
      activated by an RRE-dependent mechanism, an Rta mutant (Rta K156A), deficient for
      DNA binding and RRE activation but competent for Zp/Rp activation, was used. Rta
      K156A failed to activate BALF5p, suggesting this promoter can be activated by an
      RRE-dependent mechanism. Rta binding to late gene promoters was not seen at early
      time points but was specifically detected at later times within the Rta
      responsive BLRF2 and BFRF3 promoters, even when DNA replication was inhibited.
      Our results represent the first characterization of Rta binding to the EBV genome
      during replication, identify previously unknown RREs, such as one in BALF5p, and
      highlight the complexity of EBV late gene promoter activation by Rta.

PMID- 22379088
TI  - Small-molecule inhibition of human immunodeficiency virus type 1 replication by
      targeting the interaction between Vif and ElonginC.
AB  - The HIV-1 viral infectivity factor (Vif) protein is essential for viral
      replication. Vif recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to
      target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. In
      the absence of Vif, A3G is packaged into budding HIV-1 virions and introduces
      multiple mutations in the newly synthesized minus-strand viral DNA to restrict
      virus replication. Thus, the A3G-Vif-E3 complex represents an attractive target
      for development of novel anti-HIV drugs. In this study, we identified a potent
      small molecular compound (VEC-5) by virtual screening and validated its anti-Vif
      activity through biochemical analysis. We show that VEC-5 inhibits virus
      replication only in A3G-positive cells. Treatment with VEC-5 increased cellular
      A3G levels when Vif was coexpressed and enhanced A3G incorporation into HIV-1
      virions to reduce viral infectivity. Coimmunoprecipitation and computational
      analysis further attributed the anti-Vif activity of VEC-5 to the inhibition of
      Vif from direct binding to the ElonginC protein. These findings support the
      notion that suppressing Vif function can liberate A3G to carry out its antiviral
      activity and demonstrate that regulation of the Vif-ElonginC interaction is a
      novel target for small-molecule inhibitors of HIV-1.

PMID- 22379089
TI  - West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type
      I interferon-mediated antiviral response.
AB  - We previously showed that a noncoding subgenomic flavivirus RNA (sfRNA) is
      required for viral pathogenicity, as a mutant West Nile virus (WNV) deficient in
      sfRNA production replicated poorly in wild-type mice. To investigate the possible
      immunomodulatory or immune evasive functions of sfRNA, we utilized mice and cells
      deficient in elements of the type I interferon (IFN) response. Replication of the
      sfRNA mutant WNV was rescued in mice and cells lacking interferon regulatory
      factor 3 (IRF-3) and IRF-7 and in mice lacking the type I alpha/beta interferon
      receptor (IFNAR), suggesting a contribution for sfRNA in overcoming the antiviral
      response mediated by type I IFN. This was confirmed by demonstrating rescue of
      mutant virus replication in the presence of IFNAR neutralizing antibodies,
      greater sensitivity of mutant virus replication to IFN-alpha pretreatment,
      partial rescue of its infectivity in cells deficient in RNase L, and direct
      effects of transfected sfRNA on rescuing replication of unrelated Semliki Forest
      virus in cells pretreated with IFN-alpha. The results define a novel function of
      sfRNA in flavivirus pathogenesis via its contribution to viral evasion of the
      type I interferon response.

PMID- 22379090
TI  - Valosin-containing protein (VCP/p97) is required for poliovirus replication and
      is involved in cellular protein secretion pathway in poliovirus infection.
AB  - Poliovirus (PV) modifies membrane-trafficking machinery in host cells for its
      viral RNA replication. To date, ARF1, ACBD3, BIG1/BIG2, GBF1, RTN3, and PI4KB
      have been identified as host factors of enterovirus (EV), including PV, involved
      in membrane traffic. In this study, we performed small interfering RNA (siRNA)
      screening targeting membrane-trafficking genes for host factors required for PV
      replication. We identified valosin-containing protein (VCP/p97) as a host factor
      of PV replication required after viral protein synthesis, and its ATPase activity
      was essential for PV replication. VCP colocalized with viral proteins 2BC/2C and
      3AB/3B in PV-infected cells and showed an interaction with 2BC and 3AB but not
      with 2C and 3A. Knockdown of VCP did not suppress the replication of
      coxsackievirus B3 or Aichi virus. A VCP-knockdown-resistant PV mutant had an
      A4881G (a mutation of E253G in 2C) mutation, which is known as a determinant of a
      secretion inhibition-negative phenotype. However, knockdown of VCP did not affect
      the inhibition of cellular protein secretion caused by overexpression of each
      individual viral protein. These results suggested that VCP is a host factor
      required for viral RNA replication of PV among membrane-trafficking proteins and
      provides a novel link between cellular protein secretion and viral RNA
      replication.

PMID- 22379091
TI  - The extended cell panel assay characterizes the relationship of prion strains
      RML, 79A, and 139A and reveals conversion of 139A to 79A-like prions in cell
      culture.
AB  - Three commonly used isolates of murine prions, 79A, 139A, and RML, were derived
      from the so-called Chandler isolate, which was obtained by propagating prions
      from scrapie-infected goat brain in mice. RML is widely believed to be identical
      with 139A; however, using the extended cell panel assay (ECPA), we here show that
      139A and RML isolates are distinct, while 79A and RML could not be distinguished.
      We undertook to clone 79A and 139A prions by endpoint dilution in murine
      neuroblastoma-derived PK1 cells. Cloned 79A prions, when returned to mouse brain,
      were unchanged and indistinguishable from RML by ECPA. However, 139A-derived
      clones, when returned to brain, yielded prions distinct from 139A and similar to
      79A and RML. Thus, when 139A prions were transferred to PK1 cells, 79A/RML-like
      prions, either present as a minor component in the brain 139A population or
      generated by mutation in the cells, were selected and, after being returned to
      brain, were the major if not only component of the population.

PMID- 22379092
TI  - A protein array screen for Kaposi's sarcoma-associated herpesvirus LANA
      interactors links LANA to TIP60, PP2A activity, and telomere shortening.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) LANA protein functions in
      latently infected cells as an essential participant in KSHV genome replication
      and as a driver of dysregulated cell growth. To identify novel LANA protein-cell
      protein interactions that could contribute to these activities, we performed a
      proteomic screen in which purified, adenovirus-expressed Flag-LANA protein was
      incubated with an array displaying 4,192 nonredundant human proteins. Sixty-one
      interacting cell proteins were consistently detected. LANA interactions with high
      mobility group AT-hook 1 (HMGA1), HMGB1, telomeric repeat binding factor 1
      (TRF1), xeroderma pigmentosum complementation group A (XPA), pygopus homolog 2
      (PYGO2), protein phosphatase 2A (PP2A)B subunit, Tat-interactive protein 60
      (TIP60), replication protein A1 (RPA1), and RPA2 proteins were confirmed in
      coimmunoprecipitation assays. LANA-associated TIP60 retained acetyltransferase
      activity and, unlike human papillomavirus E6 and HIV-1 TAT proteins, LANA did not
      reduce TIP60 stability. The LANA-bound PP2A B subunit was associated with the
      PP2A A subunit but not the catalytic C subunit, suggesting a disruption of PP2A
      phosphatase activity. This is reminiscent of the role of simian virus 40 (SV40)
      small t antigen. Chromatin immunoprecipitation (ChIP) assays showed binding of
      RPA1 and RPA2 to the KSHV terminal repeats. Interestingly, LANA expression
      ablated RPA1 and RPA2 binding to the cell telomeric repeats. In U2OS cells that
      rely on the alternative mechanism for telomere maintenance, LANA expression had
      minimal effect on telomere length. However, LANA expression in telomerase
      immortalized endothelial cells resulted in telomere shortening. In KSHV-infected
      cells, telomere shortening may be one more mechanism by which LANA contributes to
      the development of malignancy.

PMID- 22379094
TI  - Characterization of novel components of the baculovirus per os infectivity factor
      complex.
AB  - Baculovirus occlusion-derived virus (ODV) infects insect midgut cells under
      alkaline conditions, a process mediated by highly conserved per os infectivity
      factors (PIFs), P74 (PIF0), PIF1, PIF2, PIF3, PIF4, and PIF5 (ODV-E56).
      Previously, a multimolecular complex composed of PIF1, PIF2, PIF3, and P74 was
      identified which was proposed to play an essential role during ODV entry.
      Recently, more proteins have been identified that play important roles in ODV
      oral infectivity, including PIF4, PIF5, and SF58, which might work in concert
      with previously known PIFs to facilitate ODV infection. In order to understand
      the ODV entry mechanism, the identification of all components of the PIF complex
      is crucial. Hence, the aim of this study was to identify additional components of
      the PIF complex. Coimmunoprecipitation (CoIP) combined with proteomic analysis
      was used to identify the components of the Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) PIF complex. PIF4 and P95 (AC83) were identified as
      components of the PIF complex while PIF5 was not, and this was confirmed with
      blue native PAGE and a second CoIP. Deletion of the pif4 gene impaired complex
      formation, but deletion of pif5 did not. Differentially denaturing SDS-PAGE
      further revealed that PIF4 forms a stable complex with PIF1, PIF2, and PIF3. P95
      and P74 are more loosely associated with this complex. Three other proteins, AC5,
      AC68, and AC108 (homologue of SF58), were also found by the proteomic analysis to
      be associated with the PIF complex. Finally the functional significance of the
      PIF protein interactions is discussed.

PMID- 22379093
TI  - The contribution of systemic and pulmonary immune effectors to vaccine-induced
      protection from H5N1 influenza virus infection.
AB  - Live attenuated influenza vaccines (LAIVs) are effective in providing protection
      against influenza challenge in animal models and in preventing disease in humans.
      We previously showed that LAIVs elicit a range of immune effectors and that
      successful induction of pulmonary cellular and humoral immunity in mice requires
      pulmonary replication of the vaccine virus. An upper respiratory tract
      immunization (URTI) model was developed in mice to mimic the human situation, in
      which the vaccine virus does not replicate in the lower respiratory tract,
      allowing us to assess the protective efficacy of an H5N1 LAIV against highly
      pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity.
      Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza
      specific lymphocytes are the main contributors to clearance of challenge virus
      from the lungs and that contributions of influenza-specific enzyme-linked
      immunosorbent assay (ELISA) antibodies in serum and splenic CD8(+) T cells were
      negligible. Complete protection from H5N1 challenge was achieved after two doses
      of H5N1 LAIV and was associated with maturation of the antibody response.
      Although passive transfer of sera from mice that received two doses of vaccine
      prevented lethality in naive recipients following challenge, the mice showed
      significant weight loss, with high pulmonary titers of the H5N1 virus. These data
      highlight the importance of mucosal immunity in mediating optimal protection
      against H5N1 infection. Understanding the requirements for effective induction
      and establishment of these protective immune effectors in the respiratory tract
      paves the way for a more rational and effective vaccine approach in the future.

PMID- 22379095
TI  - Myxoma virus M064 is a novel member of the poxvirus C7L superfamily of host range
      factors that controls the kinetics of myxomatosis in European rabbits.
AB  - The myxoma virus (MYXV) carries three tandem C7L-like host range genes (M062R,
      M063R, and M064R). However, despite the fact that the sequences of these three
      genes are similar, they possess very distinctive functions in vivo. The role of
      M064 in MYXV pathogenesis was investigated and compared to the roles of M062 and
      M063. We report that M064 is a virulence factor that contributes to MYXV
      pathogenesis but lacks the host range properties associated with M062 and M063.

PMID- 22379096
TI  - Identification of the target cells and sequence of infection during experimental
      infection of ovine fetuses with Cache Valley virus.
AB  - Cache Valley virus-induced malformations have been previously reproduced in ovine
      fetuses; however, no studies have established the course of infection of cells
      and tissues with Cache Valley virus. To address these questions, ovine fetuses at
      35 days of gestation were inoculated in utero with Cache Valley virus and
      euthanized at 7, 10, 14, 21, and 28 days postinfection. On postmortem
      examination, arthrogryposis and oligohydramnios were observed in some infected
      fetuses. Morphological studies showed necrosis in the central nervous system and
      skeletal muscle of infected fetuses evaluated after 7 to 14 days postinfection,
      and hydrocephalus, micromyelia, and muscular loss were observed in infected
      fetuses after 21 to 28 days postinfection. Using immunohistochemistry and in situ
      hybridization, intense Cache Valley virus antigen and RNA staining was detected
      in the brain, spinal cord, skeletal muscle, and, to a lesser degree, in fetal
      membranes and other tissues of infected fetuses. Viral antigen and RNA staining
      decreased in targeted and infected tissues with the progression of the infection.

PMID- 22379097
TI  - Influenza virus H1N1pdm09 infections in the young and old: evidence of greater
      antibody diversity and affinity for the hemagglutinin globular head domain (HA1
      Domain) in the elderly than in young adults and children.
AB  - The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected
      features, including low morbidity and mortality in older populations. We
      performed in-depth evaluation of antibody responses generated following H1N1pdm09
      infection of naive ferrets and of 130 humans ranging from the very young (0 to 9
      years old) to the very old (70 to 89 years old). In addition to hemagglutination
      inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display
      libraries (GFPDL) to evaluate the antibody repertoires against internal genes,
      hemagglutinin (HA), and neuraminidase (NA) and also measured antibody affinity
      for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets
      demonstrated gradual development of antibody repertoires with a focus on M1 and
      HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70
      years old) induced antibodies with broader epitope recognition in both the
      internal genes and the HA1 receptor binding domain (RBD) than for the younger age
      groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from
      the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1)
      (but not HA2) than those from younger subjects (50% versus <22% 7 M urea
      resistance, respectively) and lower antibody dissociation rates using surface
      plasmon resonance. This is the first study in humans that provides evidence for a
      qualitatively superior antibody response in the elderly following H1N1pdm09
      infection, indicative of recall of long-term memory B cells or long-lived plasma
      cells. These findings may help explain the age-related morbidity and mortality
      pattern observed during the H1N1pdm09 pandemic.

PMID- 22379098
TI  - Four amino acids of an insect densovirus capsid determine midgut tropism and
      virulence.
AB  - Densoviruses are insect parvoviruses that are orally infectious for Lepidoptera.
      To assess the mechanisms underlying their specificity and their virulence, we
      investigated the role of eight candidate residues in the densovirus capsid. We
      showed that the substitutions of four amino acids were associated with decreased
      virulence due to a decreased ability to cross the host midgut epithelium, without
      an effect on viral replication in other tissues.

PMID- 22379099
TI  - Retroviral cyclin enhances cyclin-dependent kinase-8 activity.
AB  - Alterations in the functional levels of cyclin-dependent kinase-8 (CDK8) or its
      partner, cyclin C, have been clearly associated with cancers, including colon
      cancer, melanoma, and osteosarcoma. Walleye dermal sarcoma virus encodes a
      retroviral cyclin (RV-cyclin) that localizes to interchromatin granule clusters
      and binds CDK8. It also binds to the Aalpha subunit (PR65) of protein phosphatase
      2A (PP2A). Binding to the Aalpha subunit excludes the regulatory B subunit, but
      not the catalytic C subunit, in a manner similar to that of T antigens of the
      small DNA tumor viruses. The expression of the RV-cyclin enhances the activity of
      immune affinity-purified CDK8 in vitro for RNA polymerase II carboxy-terminal
      domain (CTD) and histone H3 substrates. PP2A also enhances CDK8 kinase activity
      in vitro for the CTD but not for histone H3. The PP2A enhancement of CDK8 is
      independent of RV-cyclin expression and likely plays a role in the normal
      regulation of CDK8. The manipulation of endogenous PP2A activity by inhibition,
      amendment, or depletion confirmed its role in CDK8 activation by triggering CDK8
      autophosphorylation. Although RV-cyclin and PP2A both enhance CDK8 activity,
      their actions are uncoupled and additive in kinase reactions. PP2A may be
      recruited to CDK8 in the Mediator complex by a specific PP2A B subunit or
      additionally by the RV-cyclin in infected cells, but the RV-cyclin appears to
      activate CDK8 directly and in a manner independent of its physical association
      with PP2A.

PMID- 22379100
TI  - Identification of novel positive-strand RNA viruses by metagenomic analysis of
      archaea-dominated Yellowstone hot springs.
AB  - There are no known RNA viruses that infect Archaea. Filling this gap in our
      knowledge of viruses will enhance our understanding of the relationships between
      RNA viruses from the three domains of cellular life and, in particular, could
      shed light on the origin of the enormous diversity of RNA viruses infecting
      eukaryotes. We describe here the identification of novel RNA viral genome
      segments from high-temperature acidic hot springs in Yellowstone National Park in
      the United States. These hot springs harbor low-complexity cellular communities
      dominated by several species of hyperthermophilic Archaea. A viral metagenomics
      approach was taken to assemble segments of these RNA virus genomes from viral
      populations isolated directly from hot spring samples. Analysis of these RNA
      metagenomes demonstrated unique gene content that is not generally related to
      known RNA viruses of Bacteria and Eukarya. However, genes for RNA-dependent RNA
      polymerase (RdRp), a hallmark of positive-strand RNA viruses, were identified in
      two contigs. One of these contigs is approximately 5,600 nucleotides in length
      and encodes a polyprotein that also contains a region homologous to the capsid
      protein of nodaviruses, tetraviruses, and birnaviruses. Phylogenetic analyses of
      the RdRps encoded in these contigs indicate that the putative archaeal viruses
      form a unique group that is distinct from the RdRps of RNA viruses of Eukarya and
      Bacteria. Collectively, our findings suggest the existence of novel positive
      strand RNA viruses that probably replicate in hyperthermophilic archaeal hosts
      and are highly divergent from RNA viruses that infect eukaryotes and even more
      distant from known bacterial RNA viruses. These positive-strand RNA viruses might
      be direct ancestors of RNA viruses of eukaryotes.

PMID- 22379101
TI  - The intertransmembrane region of Kaposi's sarcoma-associated herpesvirus
      modulator of immune recognition 2 contributes to B7-2 downregulation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor virus, encodes two
      homologous membrane-associated E3 ubiquitin ligases, modulator of immune
      recognition 1 (MIR1) and MIR2, to evade host immunity. Both MIR1 and MIR2
      downregulate the surface expression of major histocompatibility complex class I
      (MHC I) molecules through ubiquitin-mediated endocytosis followed by lysosomal
      degradation. Since MIR2 additionally downregulates a costimulatory molecule (B7
      2) and an integrin ligand (intercellular adhesion molecule 1 [ICAM-1]), MIR2 is
      thought to be a more important molecule for immune evasion than MIR1; however,
      the molecular basis of the MIR2 substrate specificity remains unclear. To address
      this issue, we determined which regions of B7-2 and MIR2 are required for MIR2
      mediated B7-2 downregulation. Experiments with chimeras made by swapping domains
      between human B7-2 and CD8alpha, a non-MIR2 substrate, and between MIR1 and MIR2
      demonstrated a significant contribution of the juxtamembrane (JM) region of B7-2
      and the intertransmembrane (ITM) region of MIR2 to MIR2-mediated downregulation.
      Structure prediction and mutagenesis analyses indicate that Phe119 and Ser120 in
      the MIR2 ITM region and Asp244 in the B7-2 JM region contribute to the
      recognition of B7-2 by MIR2. This finding provides new insight into the molecular
      basis of substrate recognition by MIR family members.

PMID- 22379102
TI  - Restored PB1-F2 in the 2009 pandemic H1N1 influenza virus has minimal effects in
      swine.
AB  - PB1-F2 is an 87- to 90-amino-acid-long protein expressed by certain influenza A
      viruses. Previous studies have shown that PB1-F2 contributes to virulence in the
      mouse model; however, its role in natural hosts-pigs, humans, or birds-remains
      largely unknown. Outbreaks of domestic pigs infected with the 2009 pandemic H1N1
      influenza virus (pH1N1) have been detected worldwide. Unlike previous pandemic
      strains, pH1N1 viruses do not encode a functional PB1-F2 due to the presence of
      three stop codons resulting in premature truncation after codon 11. However,
      pH1N1s have the potential to acquire the full-length form of PB1-F2 through
      mutation or reassortment. In this study, we assessed whether restoring the full
      length PB1-F2 open reading frame (ORF) in the pH1N1 background would have an
      effect on virus replication and virulence in pigs. Restoring the PB1-F2 ORF
      resulted in upregulation of viral polymerase activity at early time points in
      vitro and enhanced virus yields in porcine respiratory explants and in the lungs
      of infected pigs. There was an increase in the severity of pneumonia in pigs
      infected with isogenic virus expressing PB1-F2 compared to the wild-type (WT)
      pH1N1. The extent of microscopic pneumonia correlated with increased pulmonary
      levels of alpha interferon and interleukin-1beta in pigs infected with pH1N1
      encoding a functional PB1-F2 but only early in the infection. Together, our
      results indicate that PB1-F2 in the context of pH1N1 moderately modulates viral
      replication, lung histopathology, and local cytokine response in pigs.

PMID- 22379103
TI  - Tacaribe virus causes fatal infection of an ostensible reservoir host, the
      Jamaican fruit bat.
AB  - Tacaribe virus (TCRV) was first isolated from 11 Artibeus species bats captured
      in Trinidad in the 1950s during a rabies virus surveillance program. Despite
      significant effort, no evidence of infection of other mammals, mostly rodents,
      was found, suggesting that no other vertebrates harbored TCRV. For this reason,
      it was hypothesized that TCRV was naturally hosted by artibeus bats. This is in
      stark contrast to other arenaviruses with known hosts, all of which are rodents.
      To examine this hypothesis, we conducted experimental infections of Jamaican
      fruit bats (Artibeus jamaicensis) to determine whether they could be persistently
      infected without substantial pathology. We subcutaneously or intranasally
      infected bats with TCRV strain TRVL-11573, the only remaining strain of TCRV, and
      found that low-dose (10(4) 50% tissue culture infective dose [TCID(50)])
      inoculations resulted in asymptomatic and apathogenic infection and virus
      clearance, while high-dose (10(6) TCID(50)) inoculations caused substantial
      morbidity and mortality as early as 10 days postinfection. Uninoculated cage
      mates failed to seroconvert, and viral RNA was not detected in their tissues,
      suggesting that transmission did not occur. Together, these data suggest that A.
      jamaicensis bats may not be a reservoir host for TCRV.

PMID- 22379104
TI  - The bovine immunodeficiency virus Rev protein: identification of a novel nuclear
      import pathway and nuclear export signal among retroviral Rev/Rev-like proteins.
AB  - The Rev protein is essential for the replication of lentiviruses. Rev is a
      shuttling protein that transports unspliced and partially spliced lentiviral RNAs
      from the nucleus to the cytoplasm via the nucleopore. To transport these RNAs,
      the human immunodeficiency virus type 1 (HIV-1) Rev uses the karyopherin beta
      family importin beta and CRM1 proteins that interact with the Rev nuclear
      localization signal (NLS) and nuclear exportation signal (NES), respectively.
      Recently, we reported the presence of new types of bipartite NLS and nucleolar
      localization signal (NoLS) in the bovine immunodeficiency virus (BIV) Rev
      protein. Here we report the characterization of the nuclear import and export
      pathways of BIV Rev. By using an in vitro nuclear import assay, we showed that
      BIV Rev is transported into the nucleus by a cytosolic and energy-dependent
      importin alpha/beta classical pathway. Results from glutathione S-transferase
      (GST) pulldown assays that showed the binding of BIV Rev with importins alpha3
      and alpha5 were in agreement with those from the nuclear import assay. We also
      identified a leptomycin B-sensitive NES in BIV Rev, which indicates that the
      protein is exported via CRM1 like HIV-1 Rev. Mutagenesis experiments showed that
      the BIV Rev NES maps between amino acids 109 to 121 of the protein. Remarkably,
      the BIV Rev NES was found to be of the cyclic AMP (cAMP)-dependent protein kinase
      inhibitor (PKI) type instead of the HIV-1 Rev type. In summary, our data showed
      that the nuclear import mechanism of BIV Rev is novel among Rev proteins
      characterized so far in lentiviruses.

PMID- 22379105
TI  - Signature biochemical properties of broadly cross-reactive HIV-1 neutralizing
      antibodies in human plasma.
AB  - The common properties of broadly cross-reactive HIV-1 neutralization antibodies
      found in certain HIV-1-infected individuals holds significant value for
      understanding natural and vaccine-mediated anti-HIV immunity. Recent efforts have
      addressed this question by deriving neutralizing monoclonal anti-envelope
      antibodies from memory B cell pools of selected subjects. However, it has been
      more difficult to identify whether broadly neutralizing antibodies circulating in
      plasma possess shared characteristics among individuals. To address this
      question, we used affinity chromatography and isoelectric focusing to fractionate
      plasma immunoglobulin from 10 HIV-1-infected subjects (5 subjects with broad HIV
      1 neutralizing activity and 5 controls). We find that plasma neutralizing
      activity typically partitions into at least two subsets of antibodies. Antibodies
      with restricted neutralization breadth have relatively neutral isoelectric points
      and preferentially bind to envelope monomers and trimers versus core antigens
      from which variable loops and other domains have been deleted. In comparison,
      broadly neutralizing antibodies account for a minor fraction of the total anti
      envelope response. They are consistently distinguished by more basic isoelectric
      points and specificity for epitopes shared by monomeric gp120, gp120 core, or CD4
      induced structures. Such biochemical properties might be exploited to reliably
      predict or produce broad anti-HIV immunity.

PMID- 22379106
TI  - Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation
      sites in live animals.
AB  - In vivo imaging involving the use of genetically engineered animals is an
      innovative powerful tool for the noninvasive assessment of the molecular and
      cellular events that are often targets of therapy. On the basis of the knowledge
      that the activity of the nuclear factor-Y (NF-Y) transcription factor is
      restricted in vitro to proliferating cells, we have generated a transgenic
      reporter mouse, called MITO-Luc (for mitosis-luciferase), in which an NF-Y
      dependent promoter controls luciferase expression. In these mice, bioluminescence
      imaging of NF-Y activity visualizes areas of physiological cell proliferation and
      regeneration during response to injury. Using this tool, we highlight for the
      first time a role of NF-Y activity on hepatocyte proliferation during liver
      regeneration. MITO-Luc reporter mice should facilitate investigations into the
      involvement of genes in cell proliferation and provide a useful model for
      studying aberrant proliferation in disease pathogenesis. They should be also
      useful in the development of new anti/proproliferative drugs and assessment of
      their efficacy and side effects on nontarget tissues.

PMID- 22379107
TI  - A mechanosensory system governs myosin II accumulation in dividing cells.
AB  - The mitotic spindle is generally considered the initiator of furrow ingression.
      However, recent studies suggest that furrows can form without spindles,
      particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme
      myosin II and the actin cross-linker cortexillin I form a mechanosensor that
      responds to mechanical stress, which could account for spindle-independent
      contractile protein recruitment. Here we show that the regulatory and
      contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6
      (kif12), and inner centromeric protein (INCENP) is a mechanical stress-responsive
      system. Myosin II and cortexillin I form the core mechanosensor, and
      mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition,
      IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the
      system, suggesting a possible mechanism for discriminating between mechanical and
      biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle
      morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is
      not directly involved in myosin II mechanosensitive accumulation, but without
      cortexillin I, cortexillin II's role in membrane-cortex attachment is revealed.
      Finally, the mitotic spindle is dispensable for the system. Overall, this
      mechanosensory system is structured like a control system characterized by
      mechanochemical feedback loops that regulate myosin II localization at sites of
      mechanical stress and the cleavage furrow.

PMID- 22379108
TI  - AUF1/hnRNP D represses expression of VEGF in macrophages.
AB  - Vascular endothelial growth factor (VEGF) is a regulator of vascularization in
      development and is a key growth factor in tissue repair. In disease, VEGF
      contributes to vascularization of solid tumors and arthritic joints. This study
      examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear
      ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression
      of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF
      protein levels. To study 3' untranslated region (UTR)-mediated regulation, we
      introduced the 3' UTR of VEGF mRNA into a luciferase reporter gene. Coexpression
      of AUF1 represses VEGF-3' UTR reporter expression in RAW-264.7 cells and in mouse
      bone marrow-derived macrophages. The C-terminus of AUF1 contains arginine-glycine
      glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of
      AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an
      AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3' UTR
      reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1
      regulates VEGF expression, and this study identifies an RGG peptide that
      suppresses VEGF gene expression.

PMID- 22379109
TI  - The endosomal adaptor protein APPL1 impairs the turnover of leading edge
      adhesions to regulate cell migration.
AB  - Cell migration is a complex process that requires the integration of signaling
      events that occur in distinct locations within the cell. Adaptor proteins, which
      can localize to different subcellular compartments, where they bring together key
      signaling proteins, are emerging as attractive candidates for controlling
      spatially coordinated processes. However, their function in regulating cell
      migration is not well understood. In this study, we demonstrate a novel role for
      the adaptor protein containing a pleckstrin-homology (PH) domain, phosphotyrosine
      binding (PTB) domain, and leucine zipper motif 1 (APPL1) in regulating cell
      migration. APPL1 impairs migration by hindering the turnover of adhesions at the
      leading edge of cells. The mechanism by which APPL1 regulates migration and
      adhesion dynamics is by inhibiting the activity of the serine/threonine kinase
      Akt at the cell edge and within adhesions. In addition, APPL1 significantly
      decreases the tyrosine phosphorylation of Akt by the nonreceptor tyrosine kinase
      Src, which is critical for Akt-mediated cell migration. Thus, our results
      demonstrate an important new function for APPL1 in regulating cell migration and
      adhesion turnover through a mechanism that depends on Src and Akt. Moreover, our
      data further underscore the importance of adaptor proteins in modulating the flow
      of information through signaling pathways.

PMID- 22379110
TI  - Incidence and prognosis of resistant hypertension in hypertensive patients.
AB  - BACKGROUND: Despite a recent American Heart Association (AHA) consensus statement
      emphasizing the importance of resistant hypertension, the incidence and prognosis
      of this condition are largely unknown. METHODS AND RESULTS: This retrospective
      cohort study in 2 integrated health plans included patients with incident
      hypertension in whom treatment was begun between 2002 and 2006. Patients were
      followed up for the development of resistant hypertension based on AHA criteria
      of uncontrolled blood pressure despite use of >=3 antihypertensive medications,
      with data collected on prescription filling information and blood pressure
      measurement. We determined incident cardiovascular events (death or incident
      myocardial infarction, heart failure, stroke, or chronic kidney disease) in
      patients with and without resistant hypertension with adjustment for patient and
      clinical characteristics. Among 205 750 patients with incident hypertension, 1.9%
      developed resistant hypertension within a median of 1.5 years from initial
      treatment (0.7 cases per 100 person-years of follow-up). These patients were more
      often men, were older, and had higher rates of diabetes mellitus than
      nonresistant patients. Over 3.8 years of median follow-up, cardiovascular event
      rates were significantly higher in those with resistant hypertension (unadjusted
      18.0% versus 13.5%, P<0.001). After adjustment for patient and clinical
      characteristics, resistant hypertension was associated with a higher risk of
      cardiovascular events (hazard ratio, 1.47; 95% confidence interval, 1.33-1.62).
      CONCLUSIONS: Among patients with incident hypertension in whom treatment was
      begun, 1 in 50 patients developed resistant hypertension. Patients with resistant
      hypertension had an increased risk of cardiovascular events, which supports the
      need for greater efforts toward improving hypertension outcomes in this
      population.

PMID- 22379111
TI  - Resistant hypertension: incidence, prevalence, and prognosis.

PMID- 22379112
TI  - The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity,
      and correlation with neurological symptoms.
AB  - BACKGROUND: This cross-sectional study provides a practical approach for the
      clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM). METHODS AND
      RESULTS: A comprehensive cardiac assessment, including standard echocardiography,
      color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and
      exercise stress testing, was performed in 205 FA patients. To assess myocardial
      hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness
      (IVSTd) was found to be the best echocardiographic parameter compared with
      cardiac magnetic resonance imaging-determined left ventricular mass. With the use
      of this parameter, 4 groups of patients with FA-CM could be defined. Patients
      with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients
      with an IVSTd exceeding the predicted normal IVSTd were classified as having mild
      FA-CM (40%) if IVSTd exceeded the normal value by <18% or as having intermediate
      FA-CM (16.1%) if IVSTd exceeded the normal value by >=18%. Patients with ejection
      fraction <50% were classified as having severe FA-CM (12.2%). In addition to
      increased myocardial mass, severe FA-CM was further characterized by dilatation
      of the left ventricle, reduced systolic strain rate of the posterior wall, and
      ECG abnormalities. Regional myocardial function correlated negatively with FA-CM
      groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no
      clear correlation was found between FA-CM groups and neurological function.
      CONCLUSIONS: We provide and describe a readily applicable clinical grouping of
      the cardiomyopathy associated with FA based on echocardiographic IVSTd and
      ejection fraction data. Because no distinct interrelations between FA-CM and
      neurological status could be determined, regular follow-up of potential cardiac
      involvement in FA patients is essential in clinical practice.

PMID- 22379113
TI  - Cardiomyopathy in Friedreich ataxia: exemplifying the challenges faced by
      cardiologists in the management of rare diseases.

PMID- 22379115
TI  - Preferential replication of systemically delivered oncolytic vaccinia virus in
      focally irradiated glioma xenografts.
AB  - PURPOSE: Radiotherapy is part of the standard of care in high-grade gliomas but
      its outcomes remain poor. Integrating oncolytic viruses with standard anticancer
      therapies is an area of active investigation. The aim of this study was to
      determine how tumor-targeted ionizing radiation (IR) could be combined with
      systemically delivered oncolytic vaccinia virus. EXPERIMENTAL DESIGN: U-87 glioma
      xenografts were grown subcutaneously or orthotopically. Oncolytic vaccinia
      viruses GLV-1h68 and LIVP 1.1.1 were injected systemically and IR was given
      focally to glioma xenografts. In a bilateral tumor model, glioma xenografts were
      grown in both flanks, oncolytic vaccinia was injected systemically and radiation
      was delivered specifically to the right flank tumor, whereas the left flank tumor
      was shielded. Viral replication and tumor regression, after systemic injection,
      was analyzed and compared in irradiated and nonirradiated glioma xenografts.
      RESULTS: Systemically administered oncolytic vaccinia virus replicated to higher
      titers in preirradiated U-87 xenografts than in nonirradiated glioma xenografts.
      This increased oncolytic viral replication correlated with increased tumor
      xenograft regression and mouse survival in subcutaneous and orthotopic U-87
      glioma models compared with monotherapies. The ability of focal IR to mediate
      selective replication of oncolytic vaccinia was shown in a bilateral glioma model
      in which systemically administered oncolytic vaccinia replicated preferentially
      in the irradiated tumor compared with the nonirradiated tumor in the same mouse.
      CONCLUSION: These findings show a potential clinical role of focal IR in
      sensitizing irradiated tumor sites for preferential vaccinia virus-mediated
      oncolysis.

PMID- 22379116
TI  - Metabolic effects of overnight continuous infusion of unacylated ghrelin in
      humans.
AB  - OBJECTIVE: To clarify the metabolic effects of an overnight i.v. infusion of
      unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely
      mediated by a still unknown ghrelin receptor subtype, including effects on beta
      cell viability and function, insulin secretion and sensitivity, and glucose and
      lipid metabolism. DESIGN: We studied the effects of a 16-h infusion (from 2100 to
      1300  h) of UAG (1.0  MUg/kg per h) or saline in eight normal subjects (age
      (mean+/-s.e.m.), 29.6+/-2.4 years; body mass index (BMI), 22.4+/-1.7  kg/m(2)),
      who were served, at 2100 and 0800  h respectively, with isocaloric balanced
      dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were
      measured every 20  min. RESULTS: In comparison with saline, UAG induced
      significant (P<0.05) changes in glucose, insulin, and FFA profiles. UAG infusion
      decreased glucose area under the curve (AUC) values by 10% (UAG(0 - 960  min):
      79.0+/-1.7*10(3)  mg/dl per min vs saline(0- 960  min): 87.5+/-3.8*10(3)  mg/dl
      per min) and the AUC at night by 14% (UAG(180)(-)(660  min): 28.4+/-0.5*10(3) 
      mg/dl per min vs saline(180 - 660  min): 33.2+/-1.1*10(3)  mg/dl per min). The
      overall insulin AUC was not significantly modified by UAG infusion; however,
      insulin AUC observed after meals was significantly increased under the exposure
      to UAG with respect to saline at either dinner or breakfast. The FFA AUC values
      were decreased by 52% under the exposure to UAG in comparison with saline (UAG(0 
      960  min): 0.3+/-0.02*10(3)  mEq/l per min vs saline(0 - 960  min): 0.6+/
      0.05*10(3)  mEq/l per min). CONCLUSIONS: Exposure to the i.v. administration of
      UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers.
      Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic
      properties.

PMID- 22379117
TI  - Serum IGF1 and insulin levels in girls with normal and precocious puberty.
AB  - OBJECTIVE: IGF1 plays an important role in growth and metabolism during puberty.
      IGF1 levels are increased in girls with central precocious puberty (CPP).
      However, the relationship with insulin before and during gonadal suppression is
      unknown. In addition, the influence of the exon 3-deleted GH receptor gene
      (GHRd3) on IGF1 levels was evaluated. DESIGN: Nine hundred and eleven healthy and
      23 early pubertal girls (15 with CPP) participated and were evaluated by dual
      energy X-ray absorptiometry (DXA) scans, fasting and oral glucose-stimulated
      insulin levels, IGF1 levels, and GHR genotyping. Fifteen girls with early puberty
      (13 with CPP) were treated with GNRH agonists and reevaluated after 3 and 12
      months. RESULTS: IGF1 and insulin levels were higher in girls with CPP compared
      with healthy controls after adjustment for age, bone age, and breast development
      (all P<=0.02). IGF1 levels were only significantly positively correlated with
      insulin levels in girls with CPP at baseline (P<=0.03). During gonadal
      suppression, changes in IGF1 levels were inversely associated with changes in
      insulin levels (P=0.04). The GHRd3/d3 genotype was associated with significantly
      higher IGF1 levels (P=0.01) but not with earlier pubertal timing in healthy
      girls. The distribution of the GHRd3 genotypes among girls with CPP did not
      differ significantly from healthy girls (P=0.2). CONCLUSION: The increased IGF1
      and insulin levels in girls with CPP may be causally interrelated. In addition,
      the GHRd3 allele positively influences IGF1 levels in a copy number-response
      relationship but not pubertal timing in healthy girls.

PMID- 22379118
TI  - Intraflagellar transport--the "new motility" 20 years later.
AB  - Intraflagellar transport is the rapid, bidirectional movement of protein
      complexes along the length of most eukaryotic cilia and flagella. Discovery of
      this intracellular process in Chlamydomonas reinhardtii 20 years ago led to a
      rapid discovery of cellular mechanisms that underlie a large number of human
      ciliopathies. Described herein are the events that led to this discovery.

PMID- 22379119
TI  - Not seeing is not believing: improving the visibility of your fluorescence
      images.
AB  - The digital age has brought both technical advances and ethical quandaries
      regarding data acquisition and image presentation in the field of cell biology.
      Image manipulation has drawn considerable attention in the past decade, leading
      to general guidelines for ethical data processing. However, effective methods of
      image presentation have been discussed only cursorily and have been largely
      overlooked. Under standard viewing conditions, the human visual system imposes
      limitations for readers analyzing fluorescence images. In this paper, I discuss
      the advantages and limitations of image-manipulation techniques with respect to
      the human visual system, including contrast stretching, nonlinear grayscale
      transformations, and pseudocoloring. While online data viewing presents
      innovative ways to access image information, most images continue to be viewed in
      static publications, in which image presentation is critical for effective
      information transmission.

PMID- 22379120
TI  - Nonequilibrium activation of a G-protein-coupled receptor.
AB  - G-protein-coupled receptor activation is generally analyzed under equilibrium
      conditions. However, real-life receptor functions are often dependent on very
      short, transient stimuli that may not allow the achievement of a steady state.
      This is particularly true for synaptic receptors such as the alpha(2A)-adrenergic
      receptor (alpha(2A)-AR). Therefore, we developed a fluorescence resonance energy
      transfer-based technology to study nonequilibrium alpha(2A)-AR function in living
      cells. To examine the effects of increasing concentrations of the endogenous
      agonist norepinephrine on the speed and extent of alpha(2A)-AR activation with
      very high temporal resolution, we took advantage of a fluorophore-containing
      alpha(2A)-AR sensor. The results indicated that the efficacy of norepinephrine in
      eliciting receptor activation increased in a time-dependent way, reaching the
      maximum with a half-life of ~60 ms. The EC(50) values under nonequilibrium
      conditions start at ~26 MUM (at 40 ms) and show a 10-fold decrease until the
      steady state is achieved. To analyze the ability of norepinephrine to trigger a
      downstream intracellular response after alpha(2A)-AR stimulation, we monitored
      the kinetics and amplitude of G(i) activation in real time by using a fluorophore
      containing G(i) sensor. The results show that both the efficacy and the potency
      of norepinephrine in inducing G(i) activation achieve a steady state more slowly,
      compared with receptor activation, and that the initial EC(50) value of ~100 nM
      decreases in an exponential way, reaching the minimal value of ~10 nM at
      equilibrium. Therefore, both the efficacy and the potency of norepinephrine
      increase ~10-fold over a few seconds of agonist stimulation, which illustrates
      that receptor and G-protein signaling and signal amplification are highly time
      dependent phenomena.

PMID- 22379122
TI  - Time for a nuclear meeting: protein trafficking and chromatin dynamics intersect
      in the plant circadian system.
AB  - Circadian clocks mediate adaptation to the 24-h world. In Arabidopsis, most
      circadian-clock components act in the nucleus as transcriptional regulators and
      generate rhythmic oscillations of transcript accumulation. In this review, we
      focus on post-transcriptional events that modulate the activity of circadian
      clock components, such as phosphorylation, ubiquitination and proteasome-mediated
      degradation, changes in cellular localization, and protein-protein interactions.
      These processes have been found to be essential for circadian function, not only
      in plants, but also in other circadian systems. Moreover, light and clock
      signaling networks are highly interconnected. In the nucleus, light and clock
      components work together to generate transcriptional rhythms, leading to a
      general control of the timing of plant physiological processes.

PMID- 22379121
TI  - Pharmacological chaperoning of nicotinic acetylcholine receptors reduces the
      endoplasmic reticulum stress response.
AB  - We report the first observation that endoplasmic reticulum (ER) stress and the
      unfolded protein response (UPR) can decrease when a central nervous system drug
      acts as an intracellular pharmacological chaperone for its classic receptor.
      Transient expression of alpha4beta2 nicotinic receptors (nAChRs) in Neuro-2a
      cells induced the nuclear translocation of activating transcription factor 6
      (ATF6), which is part of the UPR. Cells were exposed for 48 h to the full agonist
      nicotine, the partial agonist cytisine, or the competitive antagonist dihydro
      beta-erythroidine; we also tested mutant nAChRs that readily exit the ER. Each of
      these four manipulations increased Sec24D-enhanced green fluorescent protein
      fluorescence of condensed ER exit sites and attenuated translocation of ATF6
      enhanced green fluorescent protein to the nucleus. However, we found no
      correlation among the manipulations regarding other tested parameters [i.e.,
      changes in nAChR stoichiometry (alpha4(2)beta2(3) versus alpha4(3)beta2(2)),
      changes in ER and trans-Golgi structures, or the degree of nAChR up-regulation at
      the plasma membrane]. The four manipulations activated 0 to 0.4% of nAChRs, which
      shows that activation of the nAChR channel did not underlie the reduced ER
      stress. Nicotine also attenuated endogenously expressed ATF6 translocation and
      phosphorylation of eukaryotic initiation factor 2alpha in mouse cortical neurons
      transfected with alpha4beta2 nAChRs. We conclude that, when nicotine accelerates
      ER export of alpha4beta2 nAChRs, this suppresses ER stress and the UPR.
      Suppression of a sustained UPR may explain the apparent neuroprotective effect
      that causes the inverse correlation between a person's history of tobacco use and
      susceptibility to developing Parkinson's disease. This suggests a novel mechanism
      for neuroprotection by nicotine.

PMID- 22379123
TI  - Genomic instability induced by alpha-pinene in Chinese hamster cell line.
AB  - Here, we report the effects of exposure of mammalian cells to alpha-pinene, a
      bicyclic monoterpene used in insecticides, solvents and perfumes. Morphological
      analysis, performed in V79-Cl3 cells exposed for 1 h to increasing concentrations
      (25 up to 50 MUM) of alpha-pinene, indicated a statistically significant increase
      in micronucleated and multinucleated cell frequencies; apoptotic cells were seen
      at 40 and 50 MUM. This monoterpene caused genomic instability by interfering with
      mitotic process; in fact, 50% of cells (versus 19% of control cells) showed
      irregular mitosis with multipolar or incorrectly localised spindles. Cytogenetic
      analysis demonstrated high-frequency hypodiploid metaphases as well as
      endoreduplicated cells and chromosome breaks. Clastogenic damage was prevalent
      over aneuploidogenic damage as demonstrated by the higher proportion of
      kinetochore-negative micronuclei. Alkaline comet confirmed that monoterpene
      exposure caused DNA lesions in a concentration-dependent manner. This damage
      probably arose by increased reactive oxygen species (ROS) production. In order to
      assess the generation of ROS, the cells were incubated with CM-H(2)DCFDA and then
      analysed by flow cytometry. Results demonstrated an increase in fluorescence
      intensity after alpha-pinene treatment indicating increased oxidative stress. On
      the whole, these findings strongly suggest that alpha-pinene is able to
      compromise genome stability preferentially through mitotic alterations and to
      damage DNA through ROS production.

PMID- 22379124
TI  - Carotid artery intima-media thickness, but not coronary artery calcium, predicts
      coronary vascular resistance in patients evaluated for coronary artery disease.
AB  - AIMS: There is growing evidence that coronary artery disease (CAD) affects not
      only the conduit epicardial coronary arteries, but also the microvascular
      coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes
      the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and
      carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and
      ultrasound, respectively, are among the available techniques to non-invasively
      assess atherosclerotic burden. An increased CAC score and C-IMT have also been
      associated with CMVD. It is therefore of interest to explore and compare the
      potential of CAC against C-IMT to predict minimal coronary vascular resistance
      (CVR). METHODS AND RESULTS: We evaluated 120 patients (mean age 56 +/- 9 years,
      58 men) without a documented history of CAD in whom obstructive CAD was excluded.
      All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress
      (15)O-water positron emission tomography (PET)/CT, during which the coronary flow
      reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly
      with increasing tertiles of C-IMT (22 +/- 6, 27 +/- 11, and 28 +/- 9 mmHg mL(
      1)min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT
      groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC
      score (23 +/- 9, 27 +/- 8, 32 +/- 10, and 32 +/- 7 mmHg mL(-1) min(-1) g(-1), P <
      0.01), whereas the CFR did not show a significant decrease with higher CAC scores
      (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but
      not CAC, was independently associated with minimal CVR. CONCLUSION: C-IMT, but
      not CAC score, independently predicts minimal CVR in patients with multiple
      cardiovascular risk factors and suspected of CAD.

PMID- 22379125
TI  - Dynamics of the tricuspid valve annulus in normal and dilated right hearts: a
      three-dimensional transoesophageal echocardiography study.
AB  - BACKGROUND: The tricuspid valve annulus (TVA) is a complex three-dimensional
      structure that is incompletely understood. Three-dimensional transoesophageal
      echo (TOE) provides us with the opportunity to examine this structure in detail.
      METHODS AND RESULTS: Fifty patients were included, divided into two groups:
      controls (n = 20), and dilated right hearts (DRH, n = 30). Three-dimensional zoom
      images of the TVA were acquired using an iE33 machine and X7-2t transducer.
      Antero-posterior (AP) diameter, septo-lateral (SL) diameter, area, circumference,
      and height were measured at 6 points of the cardiac cycle adapting commercially
      available software designed for assessing the mitral valve (MVQ, Philips). The
      eccentricity ratio was calculated as AP/SL. The tricuspid annular area decreases
      during systole in both groups, and is greatest in mid-diastole. The area is
      significantly larger in the DRH group (mean 1566 mm(2) DRH vs. 1097 mm(2)
      controls; P < 0.01). The SL diameter increases proportionately more in the DRH
      group, resulting in a more circular orifice and lower eccentricity ratios
      (eccentricity ratio mean 1.01 DRH vs. 1.24 controls; P < 0.01). The dynamic
      diastolic to systolic change in the SL diameter is lost in patients with DRH,
      contributing to the more circular TVA orifice throughout systole. CONCLUSION:
      Three-dimensional TOE allows us to examine the TVA in great detail. In patients
      with DRH, the TVA dilates in a SL direction, resulting in a more circular
      orifice. The dynamic changes of the TVA are lost in patients with DRH,
      potentially contributing to functional tricuspid regurgitation.

PMID- 22379126
TI  - Ostium secundum atrial septal defect and partial anomalous pulmonary venous
      connection.

PMID- 22379127
TI  - Pneumopericardium as a first sign of oesophageal perforation: the role of
      echocardiography.

PMID- 22379128
TI  - Persistent dysfunction of viable myocardium after revascularization in chronic
      ischaemic heart disease: implications for dobutamine stress echocardiography with
      longitudinal systolic strain and strain rate measurements.
AB  - AIMS: Studies of functional recovery after revascularization in chronic coronary
      artery disease are contradictory and mark a lack of knowledge of persistent
      dysfunction in the non-scarred myocardium. Based on tissue Doppler-derived
      regional longitudinal systolic strain and strain rate (SR), both at rest and
      during dobutamine stress (DS), we assessed to what extent ischaemia-related
      reduced myocardial function would recover after revascularization in hearts with
      predominantly viable myocardium. METHODS AND RESULTS: Reference peak systolic
      strain and SR values were determined from tissue Doppler imaging in 15 healthy
      volunteers. Fifty-seven patients scheduled for coronary artery bypass grafting
      (CABG), with an average ejection fraction of 49%, underwent pre-operative
      magnetic resonance imaging (MRI) with late enhancement, resting echocardiography,
      and DS echocardiography (DSE), with assessment of systolic strain and SR and post
      systolic strain (PSS). Eight to 10 months after CABG, myocardial function was
      reassessed. Forty per cent of all segments had reduced longitudinal systolic
      strain pre-operatively despite only 1.4% of segments with transmural infarctions
      on MRI. After revascularization, 38% of prior dysfunctional segments improved
      their resting strain, whereas 72% were improved by DS. Positive resting systolic
      strain indicated the absence of significant scar tissue. Resting systolic strain
      and DS strain responses were good prognosticators for functional improvement with
      areas under the receiver operating characteristic curve of 0.753 (0.646-0.860)
      and 0.790 (0.685-0.895), respectively. CONCLUSION: Persistently reduced
      longitudinal function was observed in more than half of pre-operatively viable
      but dysfunctional segments after CABG. We propose that such a functional
      impairment marks a regional remodelling process not amendable to re-established
      blood flow.

PMID- 22379129
TI  - A meta-analysis of left ventricular dyssynchrony assessment and prediction of
      response to cardiac resynchronization therapy by three-dimensional
      echocardiography.
AB  - AIMS: In a time of controversy regarding the use of echocardiography for
      assessment of left ventricular (LV) dyssynchrony and prediction of response to
      cardiac resynchronization therapy (CRT), this meta-analysis aimed to evaluate the
      feasibility and reliability of LV dyssynchrony assessment by three-dimensional
      echocardiography (3DE), determine clinically useful reference values in healthy
      subjects and heart failure patients, and examine the accuracy of 3DE to predict
      response to CRT. METHODS AND RESULTS: A total of 73 studies that evaluated the
      assessment of LV dyssynchrony by 3DE were eligible. The systolic dyssynchrony
      index (SDI) for 16 segments, being the predominant 3DE dyssynchrony parameter,
      was used for data pooling. Results demonstrated that LV dyssynchrony assessment
      by 3DE is feasible in 94% of studied subjects [95% confidence interval (CI): 92
      95%)]. Pooled estimates of intraclass correlation coefficients (ICC) and limits
      of agreement (LoA) demonstrated that SDI has good interobserver (ICC: 0.92, LoA:
      4.07%) and intraobserver reliability (ICC: 0.95, LoA: 2.10%). Reference values of
      SDI in healthy subjects, heart failure patients in general, and patients eligible
      for CRT were 2.7 +/- 0.9%, 9.8 +/- 3.9%, and 10.7 +/- 3.6%, respectively. Meta
      regression analysis demonstrated that reference values of SDI in healthy subjects
      significantly differed between different software [1.80% (95% CI: 0.55-3.05%), P<
      0.001]. In patients eligible for CRT, SDI had good accuracy to predict treatment
      response with a weighted mean cut-off value of 9.8% and pooled estimates for
      sensitivity and specificity of 93% (95% CI: 89-97%) and 75% (95% CI: 58-93%),
      respectively. CONCLUSION: 3DE is a feasible and reliable tool for assessment of
      LV dyssynchrony and may have additional value to current selection criteria for
      accurate prediction of response to CRT.

PMID- 22379130
TI  - Idiopathic pulmonary artery aneurysm compressing the left main coronary artery.

PMID- 22379131
TI  - Effects of enamel deproteinization on bracket bonding with conventional and resin
      modified glass ionomer cements.
AB  - The objective of this study was to test the effects of enamel deproteinization on
      bracket bonding with conventional and resin-modified glass ionomer cement
      (RMGIC). One hundred premolars, extracted for orthodontic reasons, were divided
      into five groups (n = 20). Group 1 (control): enamel was etched with 35 per cent
      phosphoric acid, a thin layer of adhesive was applied, and the brackets were
      bonded with Transbond XT. Group 2: enamel was etched with 10 per cent polyacrylic
      acid and the brackets were bonded with conventional glass ionomer cement (GIC).
      Group 3: enamel was treated with 5.25 per cent NaOCl, etched with 10 per cent
      polyacrylic acid, and the brackets were bonded with conventional GIC. Group 4:
      enamel was etched with 10 per cent polyacrylic acid and the brackets were bonded
      with RMGIC. Group 5: enamel was treated with 5.25 per cent NaOCl, etched with 10
      per cent polyacrylic acid, and the brackets were bonded with RMGIC. The teeth
      were stored in distilled water for 24 hours before they were submitted to shear
      testing. The results demonstrated that bond strength values of group 1 (17.08 +/-
      6.39 MPa) were significantly higher in comparison with the other groups. Groups 2
      (3.43 +/- 1.94 MPa) and 3 (3.92 +/- 1.57 MPa) presented values below the average
      recommended in the literature. With regard to adhesive remnant index, the groups
      in which the enamel was treated with NaOCl showed a behaviour similar to that of
      the resin composite. It is conclude with enamel treatment with NaOCl increased
      bonding strength of brackets bonded with GIC and RMGIC, but increased bond
      strength was not statistically significant when compared to the untreated groups.

PMID- 22379132
TI  - The influence of combined orthodontic-orthognathic surgical treatment on
      perceptions of attractiveness: a longitudinal study.
AB  - The purpose of this investigation was to quantitatively evaluate the influence of
      completing the orthognathic treatment process on patients' perceptions of
      attractiveness and their desire for surgical correction. The mandibular
      prominence of an idealized profile image was altered in 2 mm increments from -16
      to 12 mm, in order to represent retrusion and protrusion of the mandible,
      respectively. These images were rated on a seven-point Likert scale by 50
      patients at T1 (pre-treatment) and T2 (6 months following orthodontic appliance
      removal). At T1, mandibular retrusion became noticeable at -4 mm and protrusion
      at 2 mm. The results remained unchanged at T2. Surgery was desired from -9 mm at
      T1 and -10 mm at T2. For mandibular protrusion, surgery was desired from 3 mm at
      T1 and 4 mm at T2. The odds of desire for surgery were reduced by 85 per cent for
      those patients who had undergone bimaxillary surgery in relation to those with
      single jaw surgery. The lowest rated images demonstrated severe degrees of
      mandibular protrusion and retrusion. The highest rated images represented the
      idealized facial profile and minor variations thereof; there was little change in
      perception between T1 and T2. Going through the process of orthognathic treatment
      does not appear to have any significant effect on patients' perceptions of facial
      profile attractiveness or the limits of mandibular sagittal deviation at which
      they would desire surgery. The clinician's information provision during treatment
      does not seem to unduly influence orthognathic patients and does not make them
      more critical of jaw deformities. 

PMID- 22379133
TI  - Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in
      response to adenylic nucleotides stress.
AB  - Transposable elements play a fundamental role in genome evolution. It is proposed
      that their mobility, activated under stress, induces mutations that could confer
      advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of
      Saccharomyces cerevisiae is activated in response to a severe deficiency in
      adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under
      these stress conditions, revealing the simultaneous activation of three active Ty
      retrotransposon families. We demonstrate that Ty1 activation in response to
      adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7.
      Ty1 is transcribed in both sense and antisense directions. We identify three Tye7
      potential binding sites in the region of Ty1 DNA sequence where antisense
      transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1
      antisense transcription. Altogether, our data suggest that, in response to
      adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA
      transcription, possibly by controlling Ty1 antisense transcription. We also
      provide the first evidence that Ty1 antisense transcription can be regulated by
      environmental stress conditions, pointing to a new level of control of Ty1
      activity by stress, as Ty1 antisense RNAs play an important role in regulating
      Ty1 mobility at both the transcriptional and post-transcriptional stages.

PMID- 22379134
TI  - The Drosophila 7SK snRNP and the essential role of dHEXIM in development.
AB  - Regulation of the positive transcription elongation factor, P-TEFb, plays a major
      role in controlling mammalian transcription and this is accomplished in part by
      controlled release of P-TEFb from the 7SK snRNP that sequesters the kinase in an
      inactive state. We demonstrate here that a similar P-TEFb control system exists
      in Drosophila. We show that an RNA previously suggested to be a 7SK homolog is,
      in fact, associated with P-TEFb, through the action of a homolog of the human
      HEXIM1/2 proteins (dHEXIM). In addition, a Drosophila La related protein (now
      called dLARP7) is shown to be the functional homolog of human LARP7. The
      Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb
      inhibitors and to nuclease treatment of cell lysates by releasing P-TEFb.
      Supporting a critical role for the d7SK snRNP in Drosophila development, dLARP7
      and dHEXIM were found to be ubiquitously expressed throughout embryos and tissues
      at all stages. Importantly, knockdown of dHEXIM was embryonic lethal, and
      reduction of dHEXIM in specific tissues led to serious developmental defects. Our
      results suggest that regulation of P-TEFb by the d7SK snRNP is essential for the
      growth and differentiation of tissues required during Drosophila development.

PMID- 22379135
TI  - Neural stem cells exposed to BrdU lose their global DNA methylation and undergo
      astrocytic differentiation.
AB  - Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) is a halogenated nucleotide of
      low toxicity commonly used to monitor DNA replication. It is considered a
      valuable tool for in vitro and in vivo studies, including the detection of the
      small population of neural stem cells (NSC) in the mammalian brain. Here, we show
      that NSC grown in self-renewing conditions in vitro, when exposed to BrdU, lose
      the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial
      differentiation, strongly up-regulating the astrocytic marker GFAP. The onset of
      GFAP expression in BrdU exposed NSC was paralleled by a reduced expression of key
      DNA methyltransferases (DNMT) and a rapid loss of global DNA CpG methylation, as
      we determined by our specially developed analytic assay. Remarkably, a known DNA
      demethylating compound, 5-aza-2'-deoxycytidine (Decitabine), had similar effect
      on demethylation and differentiation of NSC. Since our key findings apply also to
      NSC derived from murine forebrain, our observations strongly suggest more caution
      in BrdU uses in stem cells research. We also propose that BrdU and its related
      substances may also open new opportunities for differentiation therapy in
      oncology.

PMID- 22379136
TI  - Aberrant growth and lethality of Arabidopsis deficient in nonsense-mediated RNA
      decay factors is caused by autoimmune-like response.
AB  - Nonsense-mediated RNA decay (NMD) is an evolutionarily conserved RNA quality
      control mechanism that eliminates transcripts containing nonsense mutations. NMD
      has also been shown to affect the expression of numerous genes, and inactivation
      of this pathway is lethal in higher eukaryotes. However, despite relatively
      detailed knowledge of the molecular basis of NMD, our understanding of its
      physiological functions is still limited and the underlying causes of lethality
      are unknown. In this study, we examined the importance of NMD in plants by
      analyzing an allelic series of Arabidopsis thaliana mutants impaired in the core
      NMD components SMG7 and UPF1. We found that impaired NMD elicits a pathogen
      defense response which appears to be proportional to the extent of NMD
      deficiency. We also demonstrate that developmental aberrations and lethality of
      the strong smg7 and upf1 alleles are caused by constitutive pathogen response
      upregulation. Disruption of pathogen signaling suppresses the lethality of the
      upf1-3 null allele and growth defects associated with SMG7 dysfunction.
      Interestingly, infertility and abortive meiosis observed in smg7 mutants is not
      coupled with impaired NMD suggesting a broader function of SMG7 in cellular
      metabolism. Taken together, our results uncover a major physiological consequence
      of NMD deficiency in Arabidopsis and revealed multifaceted roles of SMG7 in plant
      growth and development.

PMID- 22379137
TI  - Budding yeast telomerase RNA transcription termination is dictated by the
      Nrd1/Nab3 non-coding RNA termination pathway.
AB  - The RNA component of budding yeast telomerase (Tlc1) occurs in two forms, a non
      polyadenylated form found in functional telomerase and a rare polyadenylated
      version with unknown function. Previous work suggested that the functional Tlc1
      polyA- RNA is processed from the polyA+ form, but the mechanisms regulating its
      transcription termination and 3'-end formation remained unclear. Here we examined
      transcription termination of Tlc1 RNA in the sequences 3' of the TLC1 gene and
      relate it to telomere maintenance. Strikingly, disruption of all probable or
      cryptic polyadenylation signals near the 3'-end blocked the accumulation of the
      previously reported polyA+ RNA without affecting the level, function or specific
      3' nucleotide of the mature polyA- form. A genetic approach analysing TLC1 3'-end
      sequences revealed that transcription terminates upstream of the polyadenylation
      sites. Furthermore, the results also demonstrate that the function of this Tlc1
      terminator depends on the Nrd1/Nab3 transcription termination pathway. The data
      thus show that transcription termination of the budding yeast telomerase RNA
      occurs as that of snRNAs and Tlc1 functions in telomere maintenance are not
      strictly dependent on a polyadenylated precursor, even if the polyA+ form can
      serve as intermediate in a redundant termination/maturation pathway.

PMID- 22379138
TI  - FANSe: an accurate algorithm for quantitative mapping of large scale sequencing
      reads.
AB  - The most crucial step in data processing from high-throughput sequencing
      applications is the accurate and sensitive alignment of the sequencing reads to
      reference genomes or transcriptomes. The accurate detection of insertions and
      deletions (indels) and errors introduced by the sequencing platform or by
      misreading of modified nucleotides is essential for the quantitative processing
      of the RNA-based sequencing (RNA-Seq) datasets and for the identification of
      genetic variations and modification patterns. We developed a new, fast and
      accurate algorithm for nucleic acid sequence analysis, FANSe, with adjustable
      mismatch allowance settings and ability to handle indels to accurately and
      quantitatively map millions of reads to small or large reference genomes. It is a
      seed-based algorithm which uses the whole read information for mapping and high
      sensitivity and low ambiguity are achieved by using short and non-overlapping
      reads. Furthermore, FANSe uses hotspot score to prioritize the processing of
      highly possible matches and implements modified Smith-Watermann refinement with
      reduced scoring matrix to accelerate the calculation without compromising its
      sensitivity. The FANSe algorithm stably processes datasets from various
      sequencing platforms, masked or unmasked and small or large genomes. It shows a
      remarkable coverage of low-abundance mRNAs which is important for quantitative
      processing of RNA-Seq datasets.

PMID- 22379139
TI  - Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and
      epigenomic features at the integration site.
AB  - The autonomous transcription of integrated retroviruses strongly depends on
      genetic and epigenetic effects of the chromatin at the site of integration. These
      effects are mostly suppressive and proviral activity can be finally silenced by
      mechanisms, such as DNA methylation and histone modifications. To address the
      role of the integration site at the whole-genome-scale, we performed clonal
      analysis of provirus silencing with an avian leucosis/sarcoma virus-based
      reporter vector and correlated the transcriptional silencing with the epigenomic
      landscape of respective integrations. We demonstrate efficient provirus silencing
      in human HCT116 cell line, which is strongly but not absolutely dependent on the
      de novo DNA methyltransferase activity, particularly of Dnmt3b. Proviruses
      integrated close to the transcription start sites of active genes into the
      regions enriched in H3K4 trimethylation display long-term stability of expression
      and are resistant to the transcriptional silencing after over-expression of
      Dnmt3a or Dnmt3b. In contrast, proviruses in the intergenic regions tend to
      spontaneous transcriptional silencing even in Dnmt3a(-/-) Dnmt3b(-/-) cells. The
      silencing of proviruses within genes is accompanied with DNA methylation of long
      terminal repeats, whereas silencing in intergenic regions is DNA methylation
      independent. These findings indicate that the epigenomic features of integration
      sites are crucial for their permissivity to the proviral expression.

PMID- 22379140
TI  - The role of N-terminus of Plasmodium falciparum ORC1 in telomeric localization
      and var gene silencing.
AB  - Plasmodium falciparum origin recognition complex 1 (ORC1) protein has been
      implicated in DNA replication and silencing var gene family. However, the
      mechanism and the domain structure of ORC1 related to the regulation of var gene
      family are unknown. Here we show that the unique N-terminus of PfORC1 (PfORC1N(1
      238)) is targeted to the nuclear periphery in vivo and this region binds to the
      telomeric DNA in vitro due to the presence of a leucine heptad repeats. Like
      PfORC1N(1-238), endogenous full length ORC1, was found to be associated with sub
      telomeric repeat regions and promoters of various var genes. Additionally,
      binding and propagation of ORC1 to telomeric and subtelomeric regions was
      severely compromised in PfSir2 deficient parasites suggesting the dependence of
      endogenous ORC1 on Sir2 for var gene regulation. This feature is not previously
      described for Plasmodium ORC1 and contrary to yeast Saccharomyces cerevisiae
      where ORC function as a landing pad for Sir proteins. Interestingly, the
      overexpression of ORC1N(1-238) compromises the binding of Sir2 at the
      subtelomeric loci and var gene promoters consistent with de-repression of some
      var genes. These results establish role of the N-terminus of PfORC1 in
      heterochromatin formation and regulation of var gene expression in co-ordination
      with Sir2 in P. falciparum.

PMID- 22379141
TI  - Assessing the impact of chronic kidney disease on individuals and populations:
      use of relative and absolute measures.

PMID- 22379142
TI  - Lung cancer detection by canine scent: will there be a lab in the lab?

PMID- 22379143
TI  - Should we abandon standard forceps biopsy to diagnose an endobronchial lesion?

PMID- 22379144
TI  - The RAGE against the storm.

PMID- 22379145
TI  - The new guidelines for management of work-related asthma.

PMID- 22379146
TI  - Perspectives in medical education: signposts to the future in educating
      respiratory specialists.

PMID- 22379147
TI  - Ten principles for clean air.

PMID- 22379148
TI  - Guidelines for the management of work-related asthma.
AB  - Work-related asthma, which includes occupational asthma and work-aggravated
      asthma, has become one of the most prevalent occupational lung diseases. These
      guidelines aim to upgrade occupational health standards, contribute importantly
      to transnational legal harmonisation and reduce the high socio-economic burden
      caused by this disorder. A systematic literature search related to five key
      questions was performed: diagnostics; risk factors; outcome of management
      options; medical screening and surveillance; controlling exposure for primary
      prevention. Each of the 1,329 retrieved papers was reviewed by two experts,
      followed by Scottish Intercollegiate Guidelines Network grading, and formulation
      of statements graded according to the Royal College of General Practitioners'
      three-star system. Recommendations were made on the basis of the evidence-based
      statements, which comprise the following major evidence-based strategic points.
      1) A comprehensive diagnostic approach considering the individual specific
      aspects is recommended. 2) Early recognition and diagnosis is necessary for
      timely and appropriate preventative measures. 3) A stratified medical screening
      strategy and surveillance programme should be applied to at-risk workers. 4)
      Whenever possible, removing exposure to the causative agent should be achieved,
      as it leads to the best health outcome. If this is not possible, reduction is the
      second best option, whereas respirators are of limited value. 5) Exposure
      elimination should be the preferred primary prevention approach.

PMID- 22379149
TI  - T-cell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB
      meningitis in non-HIV patients.

PMID- 22379150
TI  - On linezolid efficacy and tolerability.

PMID- 22379152
TI  - Obstructive lung function in sarcoidosis may be missed, especially in older white
      patients.

PMID- 22379151
TI  - Octreotide treatment of idiopathic pulmonary fibrosis: a proof-of-concept study.

PMID- 22379153
TI  - Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar
      proteinosis.

PMID- 22379154
TI  - Deficit of osteoprotegerin release by osteoblasts from a patient with cystic
      fibrosis.

PMID- 22379155
TI  - High frequency of voriconazole-related phototoxicity in cystic fibrosis patients.

PMID- 22379156
TI  - Comment on: Effect of a nicotine-free inhalator as part of a smoking cessation
      programme.

PMID- 22379157
TI  - Comment on: Effect of a nicotine-free inhalator as part of a smoking cessation
      programme.

PMID- 22379159
TI  - Upper age limit for bronchiolitis: 12 months or 6 months?

PMID- 22379161
TI  - Increased lung neutrophil apoptosis and inflammation resolution.

PMID- 22379163
TI  - Chest radiotherapy to achieve lung volume reduction.

PMID- 22379166
TI  - The challenge of breathlessness in the detection of pulmonary hypertension.

PMID- 22379167
TI  - The fifth world symposium on pulmonary hypertension will REVEAL the impact of
      registries.

PMID- 22379168
TI  - How can we reduce the mortality of invasive pneumococcal disease?

PMID- 22379169
TI  - REVEAL: a contemporary US pulmonary arterial hypertension registry.

PMID- 22379170
TI  - Pulmonary hypertension: the science behind the disease spectrum.
AB  - Pulmonary hypertension (PH) is a complex, multifactorial disorder divided into
      five major subtypes according to pathological, pathophysiological and therapeutic
      characteristics. Although there are distinct differences between the PH
      categories, a number of processes are common to the pathology of all subtypes.
      Vasoconstriction, as a result of endothelial dysfunction and an imbalance in the
      levels of vasoactive mediators, is a well-characterised contributory mechanism.
      Excessive cell proliferation and impaired apoptosis in pulmonary vessels leading
      to structural remodelling is most evident in pulmonary arterial hypertension
      (PAH), and several factors have been implicated, including mitochondrial
      dysfunction and mutations in bone morphogenetic protein receptor type 2.
      Inflammation plays a key role in the development of PH, with increased levels of
      many cytokines and chemokines in affected patients. Exciting insights into the
      role of angiogenesis and bone marrow-derived endothelial progenitor cells in
      disease progression have also recently been revealed. Furthermore, there is
      increasing interest in changes in the right ventricle in PH and the role of
      metabolic abnormalities. Despite considerable progress in our understanding of
      the molecular mechanisms of PH, further research is required to unravel and
      integrate the molecular changes into a better understanding of the
      pathophysiology of PH, particularly in non-PAH, to put us in a better position to
      use this knowledge for improved treatments.

PMID- 22379171
TI  - Risk factors for chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary
      hypertension caused by obstruction and vascular remodelling of pulmonary arteries
      following pulmonary embolism. Risk factors that predispose patients to CTEPH
      include the size of the initial thrombus and numerous associated host or medical
      conditions. Haemostatic risk factors include elevated levels of factor VIII and
      phospholipid antibodies or intrinsic abnormalities in fibrinogen. Medical
      conditions that are associated with an increased risk of CTEPH include a history
      of splenectomy, cancer, ventriculoatrial shunt, chronic inflammatory disease,
      antiphospholipid antibodies and hypothyroidism. Although CTEPH is potentially
      curable by pulmonary endarterectomy (PEA), up to 40% of patients evaluated for
      PEA may be denied surgery depending on the level of surgical experience and
      disease accessibility after pre-operative assessment. Furthermore, an estimated
      10-15% of patients are at risk for residual pulmonary hypertension following PEA
      surgery, due to significant concomitant small-vessel disease. However, pre
      operative identification of small-vessel involvement remains a challenge. The
      current medications effective in the treatment of pulmonary arterial hypertension
      have not demonstrated efficacy in CTEPH. Accordingly, identification of CTEPH,
      followed by early referral for evaluation and treatment by an experienced PEA
      centre, is recommended.

PMID- 22379172
TI  - State-of-the-art chronic thromboembolic pulmonary hypertension diagnosis and
      management.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease
      caused by chronic obstruction of pulmonary artery branches following episodes of
      pulmonary embolism and incomplete thrombus resolution. The prognosis of patients
      with CTEPH is poor unless an early diagnosis is made and treatment is initiated.
      Chest radiography and echocardiography are used in the initial assessment of
      suspected pulmonary hypertension. A diagnosis of CTEPH may be confirmed by the
      presence of a mismatched wedge-shaped perfusion deficit during
      ventilation/perfusion scintigraphy or characteristic findings during multi-slice
      computed tomography (CT) angiography, including a mosaic perfusion pattern,
      dilatation of proximal pulmonary arteries and right heart chambers, and the
      presence of vascular stenosis or obstruction. Prior to possible surgery,
      pulmonary angiography remains the definitive diagnostic technique, indicating the
      site and accessibility of the obstruction. However, many centres utilise CT and
      magnetic resonance imaging following recent advances in these noninvasive
      techniques. Haemodynamic evaluation via right heart catheterisation is also
      mandatory, as pulmonary vascular resistance is the most important determinant of
      both prognosis and the risk associated with pulmonary endarterectomy surgery.
      Accurate CTEPH diagnosis and characterisation of its extent and distribution are
      imperative to allow the prompt initiation of treatment, particularly surgical
      pulmonary endarterectomy in eligible patients.

PMID- 22379173
TI  - How to detect disease progression in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rapidly progressive disease,
      ultimately leading to right heart failure and death. Accumulating evidence
      indicates that intervention early in disease progression results in better
      outcomes than delaying treatment. In this review we will discuss the assessments
      and strategies that can be used to monitor disease progression and guide clinical
      management. Many tools, such as symptoms, functional classification, exercise
      capacity, haemodynamic measures, findings on cardiac imaging and levels of
      biomarkers, have shown to be prognostic for survival both at diagnosis and during
      treatment. However, attempts to define goal thresholds have produced a variety of
      results. Several groups have developed risk calculators to estimate individual
      patients' mortality risk, but the accuracy of these tools across different
      patient populations remains unknown. What is clear is the importance of regularly
      assessing a range of parameters and then tailoring treatment goals to each
      patient. In addition, the use of a multidisciplinary team approach is crucial in
      order to support patients through all aspects of managing their condition. There
      is still an urgent need for prospective collaborative initiatives to assess novel
      goals and improve treatment strategies that would allow physicians to personalise
      and optimise clinical management for their patients with PAH.

PMID- 22379174
TI  - Recent advances in the pathogenesis and clinical evaluation of pulmonary
      fibrosis.
AB  - Interstitial lung diseases (ILDs) are a group of heterogeneous disorders, either
      idiopathic or associated with injurious or inflammatory causes, in which the
      major site of damage is the lung interstitium. For a long time, knowledge
      regarding pathogenesis was trivial and there were difficulties in diagnosing and
      subsequently treating these diseases. During the past decade, however, there has
      been an impressive development in the field of ILDs. Idiopathic pulmonary
      fibrosis, the most common and fatal form of ILD, was initially believed to be due
      to an inflammatory response to unknown lung injury, whereas nowadays it is
      believed to be the result of multiple injuries at different sites of the lung
      followed by aberrant repair. The integration of clinical, radiological and
      histological data, namely a multidisciplinary team (MDT) approach, has provided
      grounds for a more accurate diagnosis of ILDs, and helped the identification of
      different entities and development of different therapeutic approaches. However,
      because of the complexity of ILDs, even this approach may fail to establish a
      confident diagnosis. How should the clinician behave in this case and what are
      the pitfalls of the MDT approach? In addition, since diagnosis is the major
      predictor of prognosis, are there any other tools available to predict prognosis?

PMID- 22379175
TI  - The remaining challenges of pneumococcal disease in adults.
AB  - Pneumococcal disease can be divided into invasive disease, i.e. when bacteria are
      detected in normally sterile body fluids, and noninvasive disease. Pneumococcal
      disease occurs more frequently in younger children and older adults. It is
      estimated that, in 2050, 30.3% of the European population will be >=65 yrs old,
      compared with 15.7% in 2000. Preventive medicine, including vaccination, is
      essential for the promotion of healthy ageing. Uptake rates for influenza
      vaccination in the elderly are generally low, despite recommendations in many
      countries. In addition, it has been reported that influenza infections can make
      people more susceptible to pneumococcal infections. Despite pneumococcal
      vaccination, case fatality rates for patients hospitalised with invasive
      pneumococcal disease have remained at around 12% since the 1950s. Even when
      effective antibiotic therapy is administered, mortality can be high amongst
      immunocompetent patients in intensive care. Timely and accurate diagnosis of
      pneumococcal disease and identification of patients at high risk of poor outcome
      is essential to ensure that adequate treatment, including hospitalisation when
      necessary, is implemented as early as possible. Improved diagnostic techniques
      and more efficacious treatments may help to reduce the burden of pneumococcal
      disease, but preventive measures, such as influenza and pneumococcal vaccination,
      should be promoted in order to avoid preventable disease, particularly in the
      elderly.

PMID- 22379176
TI  - Repeated cross-sectional survey of patient-reported asthma control in Europe in
      the past 5 years.
AB  - Although the main goal of asthma management guidelines is to achieve and maintain
      clinical control, reported levels of not well-controlled asthma remain high. The
      aim of this analysis was to compare the levels of asthma control and the
      associated impact on patients' health status in Europe in 2006, 2008 and 2010. An
      additional outcome was the comparison of the burden of asthma with diabetes. Data
      were obtained from the cross-sectional, self-reported, European National Health
      and Wellness Surveys conducted in France, Germany, Italy, Spain and the UK.
      Asthma control (Asthma Control TestTM; QualityMetric, Inc., Lincoln, RI, USA) and
      health status (Short Form (SF)-12 health survey and the Work Productivity Loss
      and Activity Impairment questionnaire) were assessed. In 2010, the proportion of
      treated asthma patients assessed as having not well-controlled asthma was 53.5%,
      compared with 56.6% and 55.0% in 2008 and 2006, respectively. A significant
      reduction in not well-controlled asthma was observed in Germany between 2006
      (72.3%) and 2010 (62.5%; p=0.005). Fluctuations in control levels were observed
      in other countries. For all surveys, having at least well-controlled asthma was
      associated with a significantly lower number of healthcare contacts in the
      previous 6 months, better mean+/-(SD) SF-12 scores for the physical (data for
      2010: not well controlled 39.9+/-11.38, at least well-controlled 48.0+/-9.89;
      p<0.001) and mental (data for 2010: not well-controlled 40.6+/-10.95, at least
      well-controlled 45.0+/-10.91; p<0.001) components, and significantly less impact
      on Work Productivity Loss and Activity Impairment. Asthma and diabetes were
      associated with a similar overall negative impact on health status. A substantial
      proportion of asthmatics remain not well-controlled across five European
      countries, resulting in a significant impact on health resources and patients'
      health status. The overall burden of asthma appears to be similar to that of
      diabetes.

PMID- 22379177
TI  - Asymptomatic bilateral pulmonary embolism in Churg-Strauss syndrome.

PMID- 22379178
TI  - Detection of Borrelia burgdorferi sensu lato in endomyocardial biopsy specimens
      in individuals with recent-onset dilated cardiomyopathy.
AB  - AIMS: Recent studies in patients with dilated cardiomyopathy (DCM) have detected
      the genome of Borrelia burgdorferi sensu lato (BBSL) in endomyocardial biopsy
      (EMB) specimens using a qualitative polymerase chain reaction (PCR), suggesting a
      causal link between Lyme disease and DCM in areas in which Lyme disease is
      endemic. We aimed to study this relationship using a comprehensive molecular
      analysis detecting BBSL in EMB samples. METHODS AND RESULTS: We performed a
      comprehensive histopathological, immunohistochemical, ultrastructural, and
      molecular analysis targeting cardiotropic viruses and BBSL in EMB specimens of 41
      individuals with recent-onset DCM and 15 controls with end-stage coronary artery
      disease. Specifically, quantitative PCR and electron microscopy of EMB specimens
      were employed. In addition, autoantibodies and manifestation of autoimmune
      diseases were evaluated in both groups. Individuals with recent-onset DCM
      presented more frequently with myocardial BBSL persistence as compared with the
      control group (24% vs. 0%, P = 0.035). In contrast, the prevalence of parvovirus
      B19 and cytomegalovirus was similar in both groups. Sequence analysis of
      borrelial DNA revealed the following genospecies: Borrelia burgdorferi sensu
      stricto in three patients (30%), Borrelia afzelii in two patients (20%), and
      Borrelia garinii in four patients (40%), the results being inconclusive in one
      case. BBSL-positive DCM patients had a higher prevalence of organ-specific
      autoimmune diseases in comparison with the remaining DCM patients (50% vs. 16%, P
      = 0.030). CONCLUSION: Myocardial persistence of BBSL may be involved in the
      pathophysiology of DCM in individuals living in areas in which Lyme disease is
      endemic.

PMID- 22379179
TI  - Ventricular tachycardia ablation in implantable cardioverter-defibrillator
      recipients: a need to catch up with current recommendations.

PMID- 22379180
TI  - Long-term outcome of transvenous bipolar atrial leads implanted in children and
      young adults with congenital heart disease.
AB  - AIMS: Atrial leads are often implanted in paediatric patients needing a pacemaker
      (PM). The aim of this study is the evaluation of their outcome in young patients.
      METHODS AND RESULTS: We evaluated transvenous atrial leads outcome in children
      and young adults from a single centre, with a retrospective analysis. A P< 0.05
      was considered significant. Between 1992 and 2008, 110 patients, 75 with
      congenital heart defects (d-transposition of great arteries status/post, s/p,
      Mustard 41%, atrioventricular septal defect 11%, tetralogy 9%, ventricular septal
      defect 8%), aged 13.3 +/- 5.3 years, underwent PM implantation with bipolar
      atrial transvenous leads for sinus node dysfunction (50%), atrioventricular block
      (38%), cardiomyopathies, and primary ventricular arrhythmias (12%). Leads are
      steroid-eluting (98%), tined (59%), screw-in (41%), polyurethane-insulated (72%),
      silicone-insulated (28%), and have been positioned by transcutaneous puncture of
      subclavian vein into right atrial appendage/remnant (RAA, 50%), right atrial free
      wall/septum (25%), left atrium (s/p Mustard, 25%). Follow-up duration is 6.4 +/-
      4.8 (range 0.1-18) years. At multivariate analysis, younger age at implant was a
      risk factor for lead failure (4 leads, 3.5%) (P= 0.03); 16 leads (14%) dislodged
      post-implantation and 12 were successfully repositioned, the others extracted or
      abandoned. Dislocation occurred more frequently with screw-in leads (P= 0.03)
      positioned outside RAA (P= 0.02). Atrial threshold showed a small but significant
      increase, 0.002 V/month (P< 0.001), impedance showed a decrease (0.6 Omega/month,
      P< 0.001), P-wave showed no significant difference. CONCLUSIONS: Transvenous
      bipolar atrial leads have good long-term results in young patients, with a very
      low rate of lead failure. Older age at implant can further reduce this rate. Lead
      dislodgement is frequent in the post-operative period.

PMID- 22379181
TI  - The importance of distal delivery of filtrate and residual water permeability in
      the pathophysiology of hyponatremia.

PMID- 22379182
TI  - End-of-life care in patients with end-stage renal disease.

PMID- 22379183
TI  - Significance of hypo- and hypernatremia in chronic kidney disease.
AB  - Both hypo- and hypernatremia are common conditions, especially in hospitalized
      patients and in patients with various comorbid conditions such as congestive
      heart failure or liver cirrhosis. Abnormal serum sodium levels have been
      associated with increased mortality in numerous observational studies. Patients
      with chronic kidney disease (CKD) represent a group with a high prevalence of
      comorbid conditions that could predispose to dysnatremias. In addition, the
      failing kidney is also characterized by a gradual development of hyposthenuria,
      and even isosthenuria, which results in further predisposition to the development
      of hypo- and hypernatremia in those with advancing stages of CKD. To date, there
      has been a paucity of population-wide assessments of the incidence and prevalence
      of dysnatremias, their clinical characteristics and the outcomes associated with
      them in patients with various stages of CKD. We review the physiology and
      pathophysiology of water homeostasis with special emphasis on changes occurring
      in CKD, the outcomes associated with abnormal serum sodium in patients with
      normal kidney function and the results of recent studies in patients with various
      stages of CKD, which indicate a substantial incidence and prevalence and
      significant adverse outcomes associated with dysnatremias in this patient
      population.

PMID- 22379184
TI  - Native kidney BK virus nephropathy associated with chronic lymphocytic leukaemia.
AB  - BK virus nephropathy (BKVN) is a well-recognized complication of renal
      transplantation. Several cases of native kidney BKVN following other solid organ
      or bone marrow transplants have been reported. We describe a patient with chronic
      lymphocytic leukaemia who presented with deteriorating renal function with no
      history of solid organ or bone marrow transplantation. Renal biopsy demonstrated
      tubular injury characteristic of viral infection, confirmed as BK virus by
      immunohistochemistry and elevated serum BK viral titres. Treatment with
      leflunomide reduced serum viral titres and stabilized renal function. This is the
      first biopsy-proven case of native kidney BKVN in a patient with no previous
      transplantation history.

PMID- 22379185
TI  - Computers in the examination room and the electronic health record: physicians'
      perceived impact on clinical encounters before and after full installation and
      implementation.
AB  - PURPOSE: We compared physicians' self-reported attitudes and behaviours regarding
      electronic health record (EHR) use before and after installation of computers in
      patient examination rooms and transition to full implementation of an EHR in a
      family medicine training practice to identify anticipated and observed effects
      these changes would have on physicians' practices and clinical encounters.
      METHODS: We conducted two individual qualitative interviews with family
      physicians. The first interview was before and second interview was 8 months
      later after full implementation of an EHR and computer installation in the
      examination rooms. Data were analysed through project team discussions and
      subsequent coding with qualitative analysis software. RESULTS: At the first
      interviews, physicians frequently expressed concerns about the potential negative
      effect of the EHR on quality of care and physician-patient interaction, adequacy
      of their skills in EHR use and privacy and confidentiality concerns.
      Nevertheless, most physicians also anticipated multiple benefits, including
      improved accessibility of patient data and online health information. In the
      second interviews, physicians reported that their concerns did not persist. Many
      anticipated benefits were realized, appearing to facilitate collaborative
      physician-patient relationships. Physicians reported a greater teaching role with
      patients and sharing online medical information and treatment plan decisions.
      CONCLUSIONS: Before computer installation and full EHR implementation, physicians
      expressed concerns about the impact of computer use on patient care. After
      installation and implementation, however, many concerns were mitigated. Using
      computers in the examination rooms to document and access patients' records along
      with online medical information and decision-making tools appears to contribute
      to improved physician-patient communication and collaboration.

PMID- 22379186
TI  - Blood pressure target attainment in the background of guidelines: the very
      elderly in Swiss primary care.
AB  - BACKGROUND: There are only a few trials for the very elderly population (>79
      years). No consensus, which blood pressure (BP) goals and substances should be
      applied, has been found yet. This survey was undertaken to investigate how
      octogenarians are treated and attain BP targets in the Swiss primary care.
      METHODS: Data from 4594 hypertensive patients were collected within 7 days. Eight
      hundred and seventy-seven patients met the requirement to be >79 years. We
      assessed substances/combinations and investigated pulse pressure and target blood
      pressure attainment (TBPA) using three different recommendations [Canadian
      Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH),
      European Society of Hypertension-European Society of Cardiology (ESH-ESC)].
      Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor
      (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel
      blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta
      blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is)
      lead to higher TBPA. Finally, we assessed the impact of drug administration,
      practical work experience, location and specialization of GPs on TBPA. RESULTS:
      Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74%
      (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65
      mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied
      followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No
      benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other
      dual combination. There was also no difference between BB/D and RAAS-I/D
      combination therapy and between single-pill combination and dual free
      combinations. CONCLUSIONS: GPs adhere to the use of substances proven in outcome
      trials and attain high TBP. No difference in meeting BP goals could be found
      using different drug classes. There is an unmet need to harmonize recommendations
      and to add additional information for the treatment of octogenarians.

PMID- 22379187
TI  - Priorities for action to improve cardiovascular preventive care of patients with
      multimorbid conditions in primary care--a participatory action research project.
AB  - BACKGROUND: Cardiovascular disease (CVD) prevention in patients with multimorbid
      conditions is not always optimal in primary care (PC). Interactive collaborative
      processes involving PC community are recommended to develop new models of care
      and to successfully reshape clinical practices. OBJECTIVE: To identify challenges
      and priorities for action in PC to improve CVD prevention among patients with
      multimorbid conditions. METHODS: Physicians (n = 6), nurses (n = 6), community
      pharmacists (n = 6), other health professionals (n = 6), patients (n = 6) and
      family members (n = 6), decision makers (n = 6) and researchers (n = 6) took part
      in a 1-day workshop. Using the Chronic Care Model (CCM) as a framework,
      participants in focus groups and nominal groups identified the challenges and
      priorities for action. RESULTS: Providing appropriate support to lifestyle change
      in patients and implementing collaborative practices are challenging. Priorities
      for action relate to three CCM domains: (i) improve the clinical information
      system by providing computerized tools for interprofessional and
      interinstitutional communication, (ii) improve the organization of health care
      and delivery system design by enhancing interprofessional collaboration,
      especially with nurses and pharmacists, and creating care teams that include a
      case manager and (iii) improve self-management support by giving patients access
      to nutritionists, to personalized health care plans including lifestyle
      recommendations and to other resources (community resources, websites).
      CONCLUSIONS: To optimize CVD prevention, PC actors recommend focussing mainly on
      three CCM domains. Electronic medical records, collaborative practices and self
      management support are perceived as pivotal aspects of successful PC prevention
      programme. Developing and implementing such models are challenging and will
      require the mobilization of the whole PC community.

PMID- 22379188
TI  - FDG-PET predicts survival in recurrent high-grade gliomas treated with
      bevacizumab and irinotecan.
AB  - Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has
      been documented in that context. This study aimed to determine the independent
      prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival
      (PFS) and overall survival (OS) of recurrent HGG after combined treatment with
      bevacizumab and irinotecan, compared with other documented prognostic variables.
      Twenty-five adult patients with histologically proven HGG were included at
      recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting
      chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed
      every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria.
      Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range,
      1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and
      72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using
      either univariate or multivariate analysis, among all variables tested:
      histological grade, Karnofsky performance status, steroid intake, and number of
      previous treatments. Moreover, FDG uptake was also prognostic of response to
      bevacizumab-based therapy. This study provides the first evidence that
      pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for
      predicting survival following anti-angiogenic therapy with bevacizumab.

PMID- 22379190
TI  - Paul Doty and the modern era of DNA as a molecule.

PMID- 22379189
TI  - HDM2 promotes WIP1-mediated medulloblastoma growth.
AB  - Medulloblastoma is the most common malignant childhood brain tumor. The protein
      phosphatase and oncogene WIP1 is over-expressed or amplified in a significant
      number of primary human medulloblastomas and cell lines. In the present study, we
      examine an important mechanism by which WIP1 promotes medulloblastoma growth
      using in vitro and in vivo models. Human cell lines and intracerebellar
      xenografted animal models were used to study the role of WIP1 and the major TP53
      regulator, HDM2, in medulloblastoma growth. Stable expression of WIP1 enhances
      growth of TP53 wild-type medulloblastoma cells, compared with cells with stable
      expression of an empty-vector or mutant WIP1. In an animal model, WIP1 enhances
      proliferation and reduces the survival of immunodeficient mice bearing
      intracerebellar xenografted human medulloblastoma cells. Cells with increased
      WIP1 expression also exhibit increased expression of HDM2. HDM2 knockdown or
      treatment with the HDM2 inhibitor Nutlin-3a, the active enantomer of Nutlin-3,
      specifically inhibits the growth of medulloblastoma cells with increased WIP1
      expression. Nutlin-3a does not affect growth of medulloblastoma cells with stable
      expression of an empty vector or of mutant WIP1. Knockdown of WIP1 or treatment
      with the WIP1 inhibitor CCT007093 results in increased phosphorylation of known
      WIP1 targets, reduced HDM2 expression, and reduced growth specifically in WIP1
      wild-type and high-expressing medulloblastoma cells. Combined WIP1 and HDM2
      inhibition is more effective than WIP1 inhibition alone in blocking growth of
      WIP1 high-expressing medulloblastoma cells. Our preclinical study supports a role
      for therapies that target WIP1 and HDM2 in the treatment of medulloblastoma.

PMID- 22379192
TI  - Pride in the profession and the Association.

PMID- 22379191
TI  - Simulated body temperature rhythms reveal the phase-shifting behavior and
      plasticity of mammalian circadian oscillators.
AB  - The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus
      maintains phase coherence in peripheral cells through metabolic, neuronal, and
      humoral signaling pathways. Here, we investigated the role of daily body
      temperature fluctuations as possible systemic cues in the resetting of peripheral
      oscillators. Using precise temperature devices in conjunction with real-time
      monitoring of the bioluminescence produced by circadian luciferase reporter
      genes, we showed that simulated body temperature cycles of mice and even humans,
      with daily temperature differences of only 3 degrees C and 1 degrees C,
      respectively, could gradually synchronize circadian gene expression in cultured
      fibroblasts. The time required for establishing the new steady-state phase
      depended on the reporter gene, but after a few days, the expression of each gene
      oscillated with a precise phase relative to that of the temperature cycles.
      Smooth temperature oscillations with a very small amplitude could synchronize
      fibroblast clocks over a wide temperature range, and such temperature rhythms
      were also capable of entraining gene expression cycles to periods significantly
      longer or shorter than 24 h. As revealed by genetic loss-of-function experiments,
      heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient
      synchronization of fibroblast oscillators to simulated body temperature cycles.

PMID- 22379193
TI  - Veterinary medical ethics. An ethicist's commentary on performing animal research
      in countries with lax regulatory structures.

PMID- 22379194
TI  - The effect of stifle angle on cranial tibial translation following tibial plateau
      leveling osteotomy: an in vitro experimental analysis.
AB  - This study was designed to determine the ability of tibial plateau leveling
      osteotomy (TPLO) to eliminate cranial tibial translation (CTT) through a loaded
      range of motion. Twenty-four large-breed canine cadaver limbs were compared. Each
      limb was placed in a custom designed jig at 120 degrees  of stifle extension
      under an axial load of 20% body weight. A force of approximately 10 N/s mimiced
      the action of the quadriceps muscle and allowed the limb to move from 120 degrees
      to maximal extension. Positional data were acquired using electromagnetic motion
      tracking sensors. Each limb was tested under normal, cranial cruciate ligament
      (CrCL)-deficient, and TPLO-treated conditions. Cranial tibial translation
      significantly increased after transection of the CrCL. The TPLO failed to
      normalize CTT within the CrCL deficient stifle; however, values trended towards
      intact values throughout the range of motion. The TPLO was more effective at
      higher angles of flexion. These altered biomechanics may help explain the
      continued progression of osteoarthritis in TPLO repaired stifles. This loaded
      model may serve as a method for future evaluation of other surgical techniques.

PMID- 22379196
TI  - Cardiopulmonary effects of using carbon dioxide for laparoscopic surgery in cats.
AB  - The cardiopulmonary effects of capnoperitoneum were investigated in 8
      spontaneously breathing, young adult female cats undergoing laparoscopic
      pancreatic biopsy (intra-abdominal pressure 12 mmHg). Cats were premedicated with
      acepromazine and hydromorphone, induced with ketamine and diazepam, and
      maintained using an end-tidal isoflurane concentration of 1.13% in 100% oxygen.
      Direct systemic arterial blood pressure, heart and respiratory rates, end-tidal
      carbon dioxide (CO(2)), and isoflurane were recorded every 5 min before
      insufflation (baseline), during insufflation of the abdomen with CO(2), and
      following desufflation. Arterial blood samples were drawn at baseline, at 10 and
      30 min of insufflation, and 5 min after desufflation for blood gases. The
      significant findings (P < 0.05) were as follows: insufflation produced an
      increase in heart rate (5 to 15 min and at 30 min), mean arterial blood pressure
      (25 to 30 min), and diastolic arterial blood pressure (10 to 30 min). After
      desufflation, respiratory rate increased for 15 min. The changes were within
      physiologically acceptable limits in these healthy, anesthetized cats despite no
      artificial maintenance of minute ventilation.

PMID- 22379195
TI  - Prevalence and genotypes of Giardia duodenalis in dairy and beef cattle in farms
      around Charlottetown, Prince Edward Island, Canada.
AB  - Prevalence of Giardia duodenalis in dairy and beef cattle on farms around
      Charlottetown, Prince Edward Island (Canada) was determined by analyzing feces
      using direct immunofluorescence antibody microscopy. Genotypes were determined by
      16S-rRNA sequencing. Fecal samples (n = 892) were collected from adult cattle in
      dairy tie-stall, dairy free-stall, and beef herds (10 herds each), and from
      calves (n = 183) from 11 dairy farms. Prevalence rates were 38% and 51% in cows
      and calves, respectively. Giardia duodenalis was present in all dairy herds, in
      9/10 beef herds and in calves from 10/11 herds examined. Prevalence rates were
      40% and 41% for cows in tie- and free-stall herds, respectively, and 27% for beef
      cows. Zoonotic Assemblage A was found in 12.2% of calves concomitantly infected
      with Assemblage E. All successfully sequenced samples (114/128) from cows
      corresponded to Assemblage E. Giardia duodenalis is highly prevalent in cattle
      herds in Prince Edward Island and Assemblage A in calves is a potential public
      health concern.

PMID- 22379197
TI  - Infectious disease prevalence in a feral cat population on Prince Edward Island,
      Canada.
AB  - Ninety-six feral cats from Prince Edward Island were used to determine the
      prevalence of selected infectious agents. The prevalence rates were 5.2% for
      feline immunodeficiency virus, 3.1% for feline leukemia virus, 3.1% for
      Mycoplasma haemofelis, 8.4% for Candidatus Mycoplasma haemominutum, 2.1% for
      Bartonella spp. and 29.8% for exposure to Toxoplasma gondii. Oocysts of T. gondii
      were detected in 1.3% of the fecal samples that were collected. Gender and
      retroviral status of the cats were significantly correlated with hemoplasma
      infections. Use of a flea comb showed that 9.6% of the cats had fleas; however,
      flea infestation was not associated with any of the infectious agents.

PMID- 22379198
TI  - Antibody titers for canine parvovirus type-2, canine distemper virus, and canine
      adenovirus type-1 in adult household dogs.
AB  - Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper
      virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031
      healthy adult household dogs (2 to 18 years old) given an annual inoculation in
      the previous 11 to 13 months. The number of dogs retaining significant titers of
      antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732
      (71%), respectively. There were no differences between males and females in
      antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly
      higher in younger dogs than in older dogs, CDV antibody was significantly higher
      in older dogs than in younger dogs, and CAV titer was not associated with age.

PMID- 22379200
TI  - Evaluation of the use of chemotherapy and other prognostic variables for
      surgically excised canine thyroid carcinoma with and without metastasis.
AB  - This retrospective study compared the efficacy of surgery alone versus surgery in
      combination with chemotherapy in the treatment of canine thyroid carcinoma;
      potential prognostic factors were evaluated. Forty-four dogs with biopsy
      confirmed thyroid carcinoma met the inclusion criteria. Twenty-eight dogs were
      treated with surgery alone and 16 with surgery and chemotherapy. The median
      survival of dogs treated with surgery and chemotherapy was 518 d, which was not
      statistically different from that of the dogs treated with surgery alone. The
      number of thyroid lobes removed at surgery was prognostic with respect to
      survival. Despite an overall metastatic rate of 48%, the addition of chemotherapy
      to surgical excision did not improve survival; however, this finding may be due
      to inadequate power to demonstrate a difference.

PMID- 22379199
TI  - [Comparison of the effects of xylazine and romifidine administered
      perioperatively on the recovery of anesthetized horses].
AB  - Comparison of the effects of xylazine and romifidine administered perioperatively
      on the recovery of anesthetized horses. The present study was designed to compare
      recoveries from anesthesia following the use of romifidine or xylazine in horses.
      In a prospective blind randomized clinical trial, 28 horses, undergoing elective
      arthroscopy, were randomly allocated into 2 groups. The intravenous anesthesia
      protocol used in the xylazine group was: butorphanol [0.02 mg/kg body weight
      (BW)] and xylazine (0.5 to 0.7 mg/kg BW) for premedication, diazepam (0.1 mg/kg
      BW) and ketamine (2.2 mg/kg BW) for induction, isoflurane in oxygen for
      maintenance and xylazine (0.1 mg/kg BW) in recovery. The xylazine was replaced
      with romifidine 0.05 to 0.08 mg/kg BW (premedication) and 0.01 mg/kg BW
      (recovery) in the romifidine group. The quality of recovery was evaluated with a
      modified scoring system and the duration recorded. Wilcoxon Ranked Sum test (P <
      0.05) was used for statistical analysis. The recovery quality scores and the
      durations of recovery were not statistically different between the 2 groups. In
      this study, romifidine and xylazine were equal in their effects on recovery
      qualities.(Translated by the authors).

PMID- 22379201
TI  - Gallbladder sludge on ultrasound is predictive of increased liver enzymes and
      total bilirubin in cats.
AB  - The purposes of this retrospective study were to assess the prevalence of
      gallbladder sludge (GBS) in a population of cats presented for abdominal
      ultrasound in a teaching hospital and to determine its association with increased
      serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total
      bilirubin (TB). Gallbladder sludge was detected in 152 (14%) of the cats
      undergoing abdominal ultrasound between 2004 and 2008. This population was
      compared to a control group of 32 cats without GBS. Alanine aminotransferase,
      ALP, and TB mean values were significantly higher in cats with GBS than in
      controls (P <= 0.0005) and odds for increased values in cats with GBS were 4.2
      [95% confidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7), and 4.1
      (95% CI: 1.5 to 11.5), respectively (P <= 0.007). In conclusion, GBS is an
      uncommon ultrasonographic finding in cats that is predictive of increased liver
      enzymes and TB. More studies are needed to establish potential links between GBS
      and hepatobiliary disease in cats.

PMID- 22379202
TI  - Eosinophilia in a cat with acute leukemia.
AB  - A 4-year-old castrated male domestic shorthaired cat with a history of vomiting
      and anorexia was diagnosed with leukemia with marked hepatic and splenic
      infiltration and concurrent eosinophilia with marked tissue infiltration. Despite
      thorough immunocytochemical and immunohistochemical immunophenotyping, the cell
      lineage of the leukemia was not identified.

PMID- 22379203
TI  - Asparaginase-associated pancreatitis in a dog.
AB  - A dog with lymphosarcoma was evaluated for vomiting, lethargy, and abdominal pain
      48 h after treatment with L-asparaginase. Based on drug administration, clinical
      signs, bloodwork, and elevated canine pancreatic lipase immunoreactivity, L
      asparaginase-associated pancreatitis was diagnosed. This is an acknowledged
      toxicity; however, its pathophysiology and incidence rate in veterinary patients
      are unknown and sparsely documented.

PMID- 22379204
TI  - Metastatic transitional cell carcinoma in proximal humerus of a dog.
AB  - Transitional cell carcinoma (TCC) was diagnosed in the proximal humerus of a dog
      that was presented with persistent right forelimb lameness with no clinical signs
      of urinary tract involvement. A diagnosis of TCC was made from surgical biopsy of
      the humeral lesion with subsequent necropsy revealing the prostatic urethra as
      the primary site of the tumor.

PMID- 22379205
TI  - Severe anemia associated with Mycoplasma wenyonii infection in a mature cow.
AB  - The clinical findings, diagnostic tests, and treatment of clinical anemia in a
      mature Angus cow infected with the hemoplasma Mycoplasma wenyonii are described.
      Mycoplasma wenyonii has been previously reported to cause clinical anemia in
      young or splenectomized cattle; however, infection has not been associated with
      severe anemia in mature animals.

PMID- 22379206
TI  - Diagnostic ophthalmology.

PMID- 22379207
TI  - Orthopedic hardware and equipment for the beginner: part 1: pins and wires.

PMID- 22379212
TI  - Integrating the public health component into the medical school curriculum.

PMID- 22379214
TI  - Closing the gap between injury prevention research and community safety promotion
      practice: revisiting the public health model.

PMID- 22379215
TI  - Health impact assessment: necessary but not sufficient for healthy public policy.

PMID- 22379216
TI  - Preventable injury deaths: a population-based proxy of child maltreatment risk in
      California.
AB  - OBJECTIVE: This study used group variations in child injury fatality rates to
      assess racial bias in the population of children identified as victims of
      maltreatment. METHODS: Injury fatality and maltreatment data from California were
      compiled for the years 1998-2007. Death and maltreatment risk ratios (RRs) and
      95% confidence intervals (CIs) were computed by race and age. Rates of excess
      child injury mortality by race were derived from three different baseline rates
      of death. Substantiations per excess injury death were calculated. RESULTS:
      compared with white children, black children faced a risk of substantiated
      maltreatment that was more than twice as great (black RR: 2.39, 95% CI 2.37,
      2.42) and were fatally injured at nearly twice the rate (black RR: 1.89, 95% CI
      1.68, 2.12). Per excess death, however, black children had rates of substantiated
      maltreatment allegations that were equivalent to or lower than the rates for
      white children. CONCLUSIONS: These data support claims that, at least in
      California, black-white racial disparities observed in maltreatment rates reflect
      real group differences in risk. These data provide no evidence of systematic
      racial bias in the child protective services' substantiation process.

PMID- 22379217
TI  - Actions to control high blood pressure among hypertensive adults in Texas
      counties along the Mexico border: Texas BRFSS, 2007.
AB  - OBJECTIVES: We examined the prevalence of actions taken to control blood pressure
      as measured by taking antihypertensive medication or making lifestyle
      modifications among hypertensive adults residing along the Texas/Mexico border.
      METHODS: We used self-reported data from the 2007 Texas Behavioral Risk Factor
      Surveillance System, with oversampling of border counties. We calculated the age
      standardized prevalence of actions taken to control hypertension by selected
      characteristics. RESULTS: In analyses that combined ethnicity with predominant
      language spoken, those least likely to take any action to control their blood
      pressure--either by taking an antihypertensive medication or by making any of
      four lifestyle modifications--were Spanish-speaking Hispanic people (83.2% +/-
      2.7% standard error [SE]), with English-speaking non-Hispanic people (88.9% +/-
      0.8% SE) having the highest prevalence of taking action to control blood
      pressure. When analyzed by type of medical category, uninsured Hispanic people
      (63.8% +/- 4.8% SE) had the lowest prevalence of taking action to control their
      blood pressure compared with uninsured non-Hispanic people (75.4% +/- 4.7% SE).
      Nonborder Texas residents with hypertension were more likely to take
      antihypertensive medications (78.4% +/- 1.0% SE) than border county residents
      with hypertension (70.7% +/- 2.0% SE). CONCLUSIONS: Public health efforts must be
      undertaken to improve the control of hypertension among residents of Texas
      counties along the Mexico border, particularly for uninsured Hispanic people.

PMID- 22379218
TI  - HIV testing and management: findings from a national sample of Asian/Pacific
      islander men who have sex with men.
AB  - OBJECTIVES: We examined reasons for and barriers to participating in HIV
      voluntary counseling and testing for Asian/Pacific Islander (A/PI) men who have
      sex with men (MSM) in the U.S. METHODS: We collected data between June 2007 and
      September 2009 in a study known as Men of Asia Testing for HIV, using a cross
      sectional community-based participatory design. This national study was conducted
      in seven U.S. metropolitan cities through a coalition of seven community-based
      organizations. RESULTS: Participants included 445 self-identified A/PI MSM aged
      >=18 years. Perception of being at risk was the number one reason for testing
      behaviors. For first-time testers, structural barriers (e.g., language barriers
      with health professionals) and fear of disclosure (e.g., sexual orientation not
      known to parents) were deterrents for nontesting in the past. Among previously
      known HIV-positive men, 22% were not seeing a doctor and 19% were not taking any
      HIV medications. CONCLUSIONS: HIV testing, care, and treatment policies would be
      less than optimal without addressing barriers to testing, including stigma
      related to sexual orientation, among A/PI MSM.

PMID- 22379219
TI  - Using emergency department data to conduct dog and animal bite surveillance in
      New York City, 2003-2006.
AB  - OBJECTIVES: Most animal bites in the United States are due to dogs, with
      approximately 4.7 million reports per year. Surveillance for dog and other animal
      bites requires a substantial investment of time and resources, and underreporting
      is common. We described the use and findings of electronic hospital emergency
      department (ED) chief complaint data to characterize patients and summarize
      trends in people treated for dog and other animal bites in New York City (NYC)
      EDs between 2003 and 2006. METHODS: Retrospective data were obtained from the
      syndromic surveillance system at the NYC Department of Health and Mental Hygiene.
      We used a statistical program to identify chief complaint free-text fields as one
      of four categories of animal bites. We evaluated descriptive statistics and
      univariate associations on the available demographic data. The findings were also
      compared with data collected through the existing passive reporting animal bite
      surveillance system. RESULTS: During the study period, more than 6,000 animal
      bite patient visits were recorded per year. The proportion of visits for animal
      bites did not appear to change over time. Dog bites accounted for more than 70%
      and cat bites accounted for 13% of animal bite patient visits. Demographic
      characteristics of patients were similar to those identified in NYC's passive
      surveillance system. CONCLUSIONS: Our findings suggest that the use of ED data
      offers a simple, less resource-intensive, and sustainable way of conducting
      animal bite surveillance and a novel use of syndromic surveillance data. However,
      it cannot replace traditional surveillance used to manage individual patients for
      potential rabies exposures.

PMID- 22379220
TI  - Passenger contact investigation associated with a transport driver with pulmonary
      tuberculosis.
AB  - OBJECTIVES: In October 2008, pulmonary tuberculosis (TB) was diagnosed in a
      driver who had transported 762 passengers in the District of Columbia
      metropolitan area during his infectious period. A passenger contact investigation
      was conducted by the six public health jurisdictions because of concern that some
      passengers might be infected with HIV or have other medical conditions that put
      them at increased risk for developing TB disease if infected. METHODS:
      Authorities evaluated 92 of 100 passengers with at least 90 minutes of cumulative
      exposure. Passengers with fewer than 90 minutes of cumulative exposure were
      evaluated if they had contacted the health department after exposure and had a
      medical condition that increased their risk of TB. A tuberculin skin test (TST)
      result of at least 5 millimeters induration was considered positive. RESULTS: Of
      153 passengers who completed TST evaluation, 11 (7%) had positive TST results.
      TST results were not associated with exposure time or high-risk medical
      conditions. No TB cases were identified in the passengers. CONCLUSIONS: The
      investigation yielded insufficient evidence that Mycobacterium tuberculosis
      transmission to passengers had occurred. TB-control programs should consider
      transportation-related passenger contact investigations low priority unless
      exposure is repetitive or single-trip exposure is long.

PMID- 22379221
TI  - The economic, institutional, and political determinants of public health delivery
      system structures.
AB  - OBJECTIVES: A typology of local public health systems was recently introduced,
      and a large degree of structural transformation over time was discovered in the
      systems analyzed. We present a qualitative exploration of the factors that
      determine variation and change in the seven structural configurations that
      comprise the local public health delivery system typology. METHODS: We applied a
      10-item semistructured telephone interview protocol to representatives from the
      local health agency in two randomly selected systems from each configuration--one
      that had maintained configuration over time and one that had changed
      configuration over time. We assessed the interviews for patterns of variation
      between the configurations. RESULTS: Four key determinants of structural change
      emerged: availability of financial resources, interorganizational relationships,
      public health agency organization, and political relationships. Systems that had
      changed were more likely to experience strengthened partnerships between public
      health agencies and other community organizations and enjoy support from policy
      makers, while stable systems were more likely to be characterized by strong
      partnerships between public health agencies and other governmental bodies and
      less supportive relationships with policy makers. CONCLUSIONS: This research
      provides information regarding the determinants of system change, and may help
      public health leaders to better prepare for the impacts of change in the areas
      discussed. It may also help those who are seeking to implement change to
      determine the contextual factors that need to be in place before change can
      happen, or how best to implement change in the face of contextual factors that
      are beyond their control.

PMID- 22379222
TI  - Local acts.

PMID- 22379223
TI  - Examining compliance with a statewide law banning junk food and beverage
      marketing in Maine schools.

PMID- 22379224
TI  - Using state laws to vaccinate the health-care workforce.

PMID- 22379226
TI  - Participatory research partnerships: addressing relevant public health system
      challenges.

PMID- 22379227
TI  - Biological physics in Mexico: Review and new challenges.
AB  - Biological and physical sciences possess a long-standing tradition of
      cooperativity as separate but related subfields of science. For some time, this
      cooperativity has been limited by their obvious differences in methods and views.
      Biological physics has recently experienced a kind of revival (or better a
      rebirth) due to the growth of molecular research on animate matter. New avenues
      for research have been opened for both theoretical and experimental physicists.
      Nevertheless, in order to better travel for such paths, the contemporary
      biological physicist should be armed with a set of specialized tools and methods
      but also with a new attitude toward multidisciplinarity. In this review article,
      we intend to somehow summarize what has been done in the past (in particular, as
      an example we will take a closer look at the Mexican case), to show some examples
      of fruitful investigations in the biological physics area and also to set a
      proposal of new curricula for physics students and professionals interested in
      applying their science to get a better understanding of the physical basis of
      biological function.

PMID- 22379228
TI  - Case for an RNA-prion world: a hypothesis based on conformational diversity.
AB  - Prions and other misfolded proteins can impart their structure and functions to
      normal molecules. Based upon a thorough structural assessment of RNA, prions and
      misfolded proteins, especially from the perspective of conformational diversity,
      we propose a case for co-existence of these in the pre-biotic world. Analyzing
      the evolution of physical aspects of biochemical structures, we put forward a
      case for an RNA-prion pre-biotic world, instead of, merely, the "RNA World".

PMID- 22379229
TI  - Responses of recurrent nets of asymmetric ON and OFF cells.
AB  - A neural field model of ON and OFF cells with all-to-all inhibitory feedback is
      investigated. External spatiotemporal stimuli drive the ON and OFF cells with,
      respectively, direct and inverted polarity. The dynamic differences between
      networks built of ON and OFF cells ("ON/OFF") and those having only ON cells
      ("ON/ON") are described for the general case where ON and OFF cells can have
      different spontaneous firing rates; this asymmetric case is generic. Neural
      responses to nonhomogeneous static and time-periodic inputs are analyzed in
      regimes close to and away from self-oscillation. Static stimuli can cause
      oscillatory behavior for certain asymmetry levels. Time-periodic stimuli expose
      dynamical differences between ON/OFF and ON/ON nets. Outside the stimulated
      region, we show that ON/OFF nets exhibit frequency doubling, while ON/ON nets
      cannot. On the other hand, ON/ON networks show antiphase responses between
      stimulated and unstimulated regions, an effect that does not rely on specific
      receptive field circuitry. An analysis of the resonance properties of both net
      types reveals that ON/OFF nets exhibit larger response amplitude. Numerical
      simulations of the neural field models agree with theoretical predictions for
      localized static and time-periodic forcing. This is also the case for simulations
      of a network of noisy integrate-and-fire neurons. We finally discuss the
      application of the model to the electrosensory system and to frequency-doubling
      effects in retina.

PMID- 22379230
TI  - Physical aspects of precision in genetic regulation.
AB  - The process by which transcription factors (TFs) locate specific DNA binding
      sites is stochastic and as such, is subject to a considerable level of noise. TFs
      diffuse in the three-dimensional nuclear space, but can also slide along the DNA.
      It was proposed that this sliding facilitates the TF molecules arriving to their
      binding site, by effectively reducing the dimensionality of diffusion. However,
      the possible implications of DNA sliding on the accuracy by which the nuclear
      concentration of TFs can be estimated were not examined. Here, we calculate the
      mean and the variance of the number of TFs that bind to their binding site in
      reduced and partially reduced diffusion dimensionality regimes. We find that a
      search process which combines three-dimensional diffusion in the nucleus with one
      dimensional sliding along the DNA can reduce the noise in TF binding and in this
      way enables a better estimation of the TF concentration inside the nucleus.

PMID- 22379231
TI  - Torque-induced deformations of charged elastic DNA rods: thin helices, loops, and
      precursors of DNA supercoiling.
AB  - We study the deformations of charged elastic rods under applied end forces and
      torques. For neutral filaments, we analyze the energetics of initial helical
      deformations and loop formation. We supplement this elastic approach with
      electrostatic energies of bent filaments and find critical conditions for
      buckling depending on the ionic strength of the solution. We also study force
      induced loop opening, for parameters relevant for DNA. Finally, some applications
      of this nano-mechanical DNA model to salt-dependent onset of the DNA supercoiling
      are discussed.

PMID- 22379232
TI  - Rater Wealth Predicts Perceptions of Outgroup Competence.
AB  - National income has a pervasive influence on the perception of ingroup
      stereotypes, with high status and wealthy targets perceived as more competent. In
      two studies we investigated the degree to which economic wealth of raters related
      to perceptions of outgroup competence. Raters' economic wealth predicted trait
      ratings when 1) raters in 48 other cultures rated Americans' competence and 2)
      Mexican Americans rated Anglo Americans' competence. Rater wealth also predicted
      ratings of interpersonal warmth on the culture level. In conclusion, raters'
      economic wealth, either nationally or individually, is significantly associated
      with perception of outgroup members, supporting the notion that ingroup
      conditions or stereotypes function as frames of reference in evaluating outgroup
      traits.

PMID- 22379233
TI  - Heart rate variability measures add a new dimension to the understanding of
      sleepiness.

PMID- 22379234
TI  - Determinants of cortical synchrony.

PMID- 22379235
TI  - Sleeping in Avon.

PMID- 22379236
TI  - Maybe it's quality not length that matters.

PMID- 22379237
TI  - Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse
      prefrontal cortex.
AB  - STUDY OBJECTIVES: The atypical antipsychotic olanzapine is used effectively for
      treating symptoms of schizophrenia and bipolar disorder. Unwanted effects of
      olanzapine include slowing of the electroencephalogram (EEG) during wakefulness
      and increased circulating levels of leptin. The mechanisms underlying the desired
      and undesired effects of olanzapine are poorly understood. Sleep and wakefulness
      are modulated by acetylcholine (ACh) in the prefrontal cortex, and leptin alters
      cholinergic transmission. This study tested the hypothesis that olanzapine
      interacts with leptin to regulate ACh release in the prefrontal cortex. DESIGN:
      Within/between subjects. SETTING: University of Michigan. PATIENTS OR
      PARTICIPANTS: Adult male C57BL/6J (B6) mice (n = 33) and B6.V-Lep(ob) (leptin
      deficient) mice (n = 31). INTERVENTIONS: Olanzapine was delivered to the
      prefrontal cortex by microdialysis. Leptin-replacement in leptin-deficient mice
      was achieved using subcutaneous micro-osmotic pumps. MEASUREMENTS AND RESULTS:
      Olanzapine caused a concentration-dependent increase in ACh release in B6 and
      leptin-deficient mice. Olanzapine was 230-fold more potent in leptin-deficient
      than in B6 mice for increasing ACh release, yet olanzapine caused a 51% greater
      ACh increase in B6 than in leptin-deficient mice. Olanzapine had no effect on
      recovery time from general anesthesia. Olanzapine increased EEG power in the
      delta (0.5-4 Hz) range. Thus, olanzapine dissociated the normal coupling between
      increased cortical ACh release, increased behavioral arousal, and EEG activation.
      Leptin replacement significantly enhanced (75%) the olanzapine-induced increase
      in ACh release. CONCLUSION: Replacing leptin by systemic administration restored
      the olanzapine-induced enhancement of ACh release in the prefrontal cortex of
      leptin-deficient mouse.

PMID- 22379238
TI  - Heart rate variability can be used to estimate sleepiness-related decrements in
      psychomotor vigilance during total sleep deprivation.
AB  - STUDY OBJECTIVES: To assess whether changes in psychomotor vigilance during sleep
      deprivation can be estimated using heart rate variability (HRV). DESIGN: HRV,
      ocular, and electroencephalogram (EEG) measures were compared for their ability
      to predict lapses on the Psychomotor Vigilance Task (PVT). SETTING: Chronobiology
      and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS:
      Twenty-four healthy Chinese men (mean age +/- SD = 25.9 +/- 2.8 years).
      INTERVENTIONS: Subjects were kept awake continuously for 40 hours under constant
      environmental conditions. Every 2 hours, subjects completed a 10-minute PVT to
      assess their ability to sustain visual attention. MEASUREMENTS AND RESULTS:
      During each PVT, we examined the electrocardiogram (ECG), EEG, and percentage of
      time that the eyes were closed (PERCLOS). Similar to EEG power density and
      PERCLOS measures, the time course of ECG RR-interval power density in the 0.02
      0.08-Hz range correlated with the 40-hour profile of PVT lapses. Based on
      receiver operating characteristic curves, RR-interval power density performed as
      well as EEG power density at identifying a sleepiness-related increase in PVT
      lapses above threshold. RR-interval power density (0.02-0.08 Hz) also classified
      subject performance with sensitivity and specificity similar to that of PERCLOS.
      CONCLUSIONS: The ECG carries information about a person's vigilance state. Hence,
      HRV measures could potentially be used to predict when an individual is at
      increased risk of attentional failure. Our results suggest that HRV monitoring,
      either alone or in combination with other physiologic measures, could be
      incorporated into safety devices to warn drowsy operators when their performance
      is impaired.

PMID- 22379239
TI  - The BDNF Val66Met polymorphism modulates sleep intensity: EEG frequency- and
      state-specificity.
AB  - STUDY OBJECTIVES: EEG slow waves are the hallmark of deep NREM sleep and may
      reflect the restorative functions of sleep. Evidence suggests that increased
      sleep slow waves after sleep deprivation reflect plastic synaptic processes, and
      that brain-derived neurotrophic factor (BDNF) is causally involved in their
      homeostatic regulation. The functional Val66Met polymorphism of the gene encoding
      pro-BDNF causes impaired activity-dependent secretion of mature BDNF protein. We
      investigated whether this polymorphism contributes to the pronounced inter
      individual variation in sleep slow wave activity (SWA) in humans. SETTING: Sleep
      laboratory in temporal isolation unit. PARTICIPANTS: Eleven heterozygous Met
      allele carriers and 11 individually sex- and age-matched Val/Val homozygotes.
      INTERVENTIONS: Forty hours prolonged wakefulness. MEASUREMENTS AND RESULTS:
      Cognitive performance, subjective state, and waking and sleep EEG in baseline and
      after sleep deprivation were studied. Val/Val homozygotes showed better response
      accuracy than Met allele carriers on a verbal 2-back working memory task. This
      difference did not reflect genotype-dependent differences in sleepiness, well
      being, or sustained attention. In baseline and recovery nights, deep stage 4
      sleep and NREM sleep intensity as quantified by EEG SWA (0.75-4.5 Hz) were higher
      in Val/Val compared to Val/Met genotype. Similar to sleep deprivation, the
      difference was most pronounced in the first NREM sleep episode. By contrast,
      increased activity in higher EEG frequencies (> 6 Hz) in wakefulness and REM
      sleep was distinct from the effects of prolonged wakefulness. CONCLUSION: BDNF
      contributes to the regulation of sleep slow wave oscillations, suggesting that
      genetically determined variation in neuronal plasticity modulates NREM sleep
      intensity in humans.

PMID- 22379240
TI  - White and gray matter abnormalities in narcolepsy with cataplexy.
AB  - STUDY OBJECTIVES: The authors applied diffusion-tensor imaging including
      measurements of mean diffusivity (MD), which is a parameter of brain tissue
      integrity, fractional anisotropy (FA), which is a parameter of neuronal fiber
      integrity, and voxel-based morphometry, which is a measure of gray and white
      matter volume, to detect brain tissue changes in patients with narcolepsy
      cataplexy. DESIGN: N/A. PATIENTS: Patients with narcolepsy-cataplexy (n = 16) and
      age-matched healthy control subjects (n = 12) were studied. INTERVENTIONS: Whole
      cerebral MD, FA measures, and the volumes of the gray and white matter
      compartments were analyzed using statistical parametric mapping. MEASUREMENT AND
      RESULTS: Significant MD increases and concomitant FA decreases were localized in
      the fronto-orbital cortex (P < 0.001) and the anterior cingulate (FA, P < 0.001;
      MD, P = 0.03) in narcolepsy-cataplexy. Additional MD increases without FA changes
      were detected in the ventral tegmental area, the dorsal raphe nuclei (P < 0.001),
      and the hypothalamus (P < 0.01). FA signal decreases were observed in the white
      matter tracts of the inferior frontal and inferior temporal cortices of
      narcolepsy-cataplexy patients (P < 0.001). Brain volume loss was evident in focal
      areas of the inferior and superior temporal cortices (P < 0.001) and the
      cingulate (P = 0.038). CONCLUSIONS: Areas of increased diffusivity in the
      hypothalamus appear consistent with hypocretinergic cell loss reported in
      narcolepsy-cataplexy. Signal abnormalities in the ventral tegmental area and the
      dorsal raphe nuclei correspond to major synaptic targets of hypocretin neurons
      that were associated with the regulation of the sleep-wake cycle. Brain tissue
      alterations identified in the frontal cortex and cingulate are crucial in the
      maintenance of attention and reward-dependent decision making, both known to be
      impaired in narcolepsy-cataplexy.

PMID- 22379241
TI  - Childhood sleep duration and associated demographic characteristics in an English
      cohort.
AB  - STUDY OBJECTIVES: To provide reference data on sleep duration throughout
      childhood and explore the demographic characteristics associated with sleep.
      DESIGN: Population-based prospective longitudinal birth-cohort study. SETTING:
      South-West England, children born in 1991-1992 and followed since birth.
      PARTICIPANTS: Eleven thousand five hundred children with repeat measures of sleep
      from birth based on parent-reported questionnaires. Data on daytime and nighttime
      sleep duration and timings and night awakenings at 8 timepoints from age 6 months
      to 11 years. RESULTS: Total sleep duration steadily fell from 13 hours and 12
      minutes during infancy to 9 hours and 49 minutes at 11 years of age. Compared
      with earlier studies, the younger children in this cohort slept for a shorter
      period. The variation in sleep duration was very wide: from 10 to 17 hours in
      early infancy, narrowing to 8.5 to 11 hours at 11 years. Half of the children at
      preschool age woke at least once during the night, but frequent waking (> 3
      times) peaked in infancy (10% of all infants) and steadily declined in the
      preschool-aged years. Despite going to bed at the same time, girls slept
      consistently longer than boys (by 5-10 minutes). Children from low-income
      families went to bed later and woke up later, but there was little difference in
      total sleep duration. Children of younger mothers (< 21 years) slept longer,
      whereas children of older mothers (> 35 years) slept persistently less. Children
      in larger families tended to go to bed later, as did the minority group of non
      White children in the cohort. CONCLUSIONS: Given the wide natural variation of
      sleep in the childhood population, any recommendations on optimal sleep duration
      at any age must take into account considerable individual variability.

PMID- 22379242
TI  - Respiratory event detection by a positive airway pressure device.
AB  - STUDY OBJECTIVES: Compare automatic event detection (AED) of respiratory events
      using a positive airway pressure (PAP) device with manual scoring of
      polysomnography (PSG) during PAP treatment of obstructive sleep apnea (OSA).
      DESIGN: Prospective PSGs of patients using a PAP device. SETTING: Six academic
      and private sleep disorders centers. PATIENTS: A total of 148 PSGs from 115
      participants with OSA (apnea-hypopnea index [AHI] >= 15 events/hr) were analyzed.
      INTERVENTIONS: A signal generated by the PAP device identifying the AED of
      respiratory events based on airflow was recorded during PSG. MEASUREMENTS AND
      RESULTS: The PSGs were manually scored without visualization of the AED signal
      and scoring of a hypopnea required a >= 4% oxygen desaturation. The apnea index
      (AI), hypopnea index (HI), and AHI by manual score and PAP AED were compared. A
      customized computer program compared individual events by manual scoring and AED
      to determine the true positive, false positive, false negative, or true negative
      events and found a sensitivity of 0.58 and a specificity of 0.98. The AHI, AI,
      and HI by the two methods were highly correlated. Bland-Altman analysis showed
      better agreement for AI than HI. Using a manually scored AHI of >= 10 events/hr
      to denote inadequate treatment, an AED AHI >= 10 events/hr had a sensitivity of
      0.58 and a specificity of 0.94. CONCLUSIONS: An AHI < 10 events/hr by PAP AED is
      usually associated with good treatment efficacy. Differences between manually
      scored and AED events were primarily due to different criteria for hypopnea
      detection.

PMID- 22379243
TI  - Insomnia in patients with COPD.
AB  - STUDY OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a leading cause
      of morbidity and mortality and may frequently be associated with sleep
      disturbances. However, the correlates of insomnia in COPD patients have not been
      well characterized. The aim of the current study was to describe the prevalence
      of insomnia disorder in COPD and to elucidate the demographic and clinical
      characteristics of COPD patients that are associated with insomnia. DESIGN: Cross
      sectional study. SETTING: Clinic-based sample from an academic hospital.
      PARTICIPANTS: Patients with stable COPD. MEASUREMENTS: An interviewer-conducted
      survey was administered to 183 participants with COPD. Seventy-two of these
      participants (30 with and 42 without insomnia) maintained a sleep diary and
      underwent actigraphy for 7 days. RESULTS: Insomnia (chronic sleep disturbance
      associated with impaired daytime functioning) was present in 27.3% of
      participants. Current tobacco users (odds ratio (OR), 2.13) and those with
      frequent sadness/anxiety (OR, 3.57) had higher odds, but oxygen use was
      associated with lower odds (OR, 0.35) of insomnia. Patients with insomnia had
      worse quality of life and a higher prevalence of daytime sleepiness. Actigraphy
      revealed shorter sleep duration and lower sleep efficiency, and a sleep diary
      revealed worse self-reported sleep quality in participants with insomnia.
      CONCLUSION: Insomnia disorder is highly prevalent in patients with COPD; current
      tobacco use and sadness/anxiety are associated with a higher prevalence, and
      oxygen use with a lower prevalence of insomnia; patients with insomnia have
      poorer quality of life and increased daytime sleepiness; and insomnia is
      associated with worse objective sleep quality.

PMID- 22379244
TI  - Increased prevalence of insomnia and changes in hypnotics use in England over 15
      years: analysis of the 1993, 2000, and 2007 National Psychiatric Morbidity
      Surveys.
AB  - STUDY OBJECTIVES: To investigate changes over 15 years in the prevalence of
      insomnia and its association with demographic characteristics and hypnotic
      medication use. DESIGN: Analysis of 3 cross-sectional national mental health
      surveys carried out in 1993, 2000, and 2007, which used comparable sampling
      methods and identical insomnia assessments. SETTING: Adults living in private
      households in England. PATIENTS OR PARTICIPANTS: 20,503 people aged 16-64 years.
      MEASUREMENTS AND RESULTS: Insomnia was defined according to 4 different criteria,
      using relevant questions from the revised Clinical Interview Schedule. Modest
      increases in insomnia prevalence were found over the survey periods (any symptoms
      increasing from 35.0% in 1993 to 38.6% in 2007; insomnia diagnosis from 3.1% to
      5.8%, respectively). In all 3 surveys, similar strengths of association in
      relation to all criteria were found, with female gender, increased age, lower
      educational attainment, depression, unemployment, economic inactivity, and
      widowed, divorced, or separated status. Prevalence of hypnotic use was double in
      2000 (0.8%) compared to 1993 (0.4%); from limited information on selected
      medications, there was no such increase between 2000 and 2007. The reasons
      reported for any sleep disturbance over the last month were generally similar
      across surveys, the most marked change being illness/discomfort increasing as an
      explanation from 14.3% to 17.4% to 19.0%. CONCLUSIONS: In the English general
      population, insomnia (by any definition) showed a modest but steady increase in
      prevalence over a 15-year period. Strengths of associations with demographic
      factors and self-reported reasons for sleep disturbance remained reasonably
      stable over this period.

PMID- 22379245
TI  - Comparative investigation of the psychophysiologic and idiopathic insomnia
      disorder phenotypes: psychologic characteristics, patients' perspectives, and
      implications for clinical management.
AB  - STUDY OBJECTIVES: Insomnia is a common disorder, yet its proposed behavioral
      phenotypes are seldom differentiated. Two consecutive studies were designed to
      investigate psychologic characteristics and treatment preferences of people with
      idiopathic insomnia (IdI) relative to psychophysiologic insomnia (PI). DESIGN:
      Cross-sectional, two-group comparison studies. SETTING: Specialized sleep
      research center. PARTICIPANTS: 40 participants (29 female, mean age 46 yr)
      participated in study 1. An additional cohort of 61 adults (48 female, mean age
      37 yr) participated in study 2. In total, samples comprised 51 participants with
      PI and 50 with IdI. All participants met diagnostic criteria for their respective
      insomnia phenotype. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Study 1
      investigated sensitivity to arousal conditioning and sleep effort using self
      report measures. Consistent with a model of conditioned arousal, participants
      with PI exhibited greater behavioral inhibition, i.e., sensitivity to threat and
      higher levels of sleep preoccupation. Study 2 investigated illness perceptions
      and cognitions and coping styles using self-report scales, and explored treatment
      acceptability based on the evaluation of 3 therapeutic scenarios. Results lend
      support to the hypothesis that IdI is considered somewhat more permanent than PI.
      Behavioral intervention was preferred to pharmacotherapy by both groups, and an
      acceptance treatment was considered more favorably by IdI study participants than
      by those with PI. CONCLUSIONS: Many similarities between IdI and PI were observed
      across psychologic measures, and both groups exhibited a preference for
      behavioral treatment. However, their distinctive characteristics appear to
      suggest that an acceptance-based therapy may also be appropriate for some people
      with IdI.

PMID- 22379246
TI  - Age and sleep disturbances among American men and women: data from the U.S.
      Behavioral Risk Factor Surveillance System.
AB  - STUDY OBJECTIVE: Explore the prevalence of sleep-related complaints across age
      groups, examining effects of sex, general health, and depressed mood. DESIGN:
      Cross-sectional analysis of data from the 2006 Behavioral Risk Factor
      Surveillance System (BRFSS). SETTING: Epidemiologic. PARTICIPANTS: Complete-case
      analysis included 155,877 participants who responded to questions related to Self
      Reported Sleep Disturbance (SLEEPDIST) and Self-Reported Tiredness/Lack of Energy
      (TIREDNESS). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Outcomes were self
      reported complaints in response to survey questions assessing SLEEPDIST and
      TIREDNESS, dichotomized as reporting a complaint < 6 versus >= 6 nights or days,
      respectively, in a 2-wk period. Predictors were age, general health, and
      depressed mood. All analyses were adjusted for race/ethnicity, income, education,
      and time since last medical checkup. Across all age groups, women reported more
      SLEEPDIST and TIREDNESS. Poor general health, mild depressed mood, and
      moderate/severe depressed mood were associated with SLEEPDIST and TIREDNESS. Both
      SLEEPDIST and TIREDNESS generally declined across the life span, with fewest
      endorsements in respondents older than 80 yr. For SLEEPDIST, odds ratios (ORs,
      reference = 80+) declined from age 18-54 yr, rose slightly, and then declined
      again after age 59 yr in men. The pattern was similar for women, except a more
      marked rise was noted from age 40-59 yr. The pattern was similar for TIREDNESS.
      CONCLUSIONS: Advancing age was not associated with increased Self-Reported Sleep
      Disturbance or Self-Reported Tiredness/Lack of Energy. These results suggest that
      the often-reported increase in sleep problems with age is a nonlinear phenomenon,
      mediated by factors other than physiologic aging.

PMID- 22379247
TI  - Developmental changes in glutamatergic fast synaptic neurotransmission in the
      dorsal subcoeruleus nucleus.
AB  - STUDY OBJECTIVES: The dorsal subcoeruleus nucleus (SubCD) is involved in the
      generation of rapid eye movement sleep (REM), a state distinguished by high
      frequency EEG activity, muscle atonia, and ponto-geniculo-occipital (PGO) waves.
      Activation of the SubCD by injection of the glutamate (GLU) receptor agonist
      kainic acid (KA) produced a REM sleep-like state with muscle atonia. We tested
      the hypothesis that developmental changes in the GLU excitability of SubCD
      neurons could underlie the developmental decrease in REM sleep that occurs in the
      rat from postnatal days 10-30. DESIGN: Sagittal sections containing the SubCD
      were cut using 9-15 day old rat pups. Whole-cell patch clamp recordings were
      performed on SubCD neurons and responses were measured following electrical
      stimulation or bath application of the GLU receptor agonists N-methyl-D-aspartic
      acid (NMDA) or KA. MEASUREMENTS AND RESULTS: Pharmacological or electrical
      stimulation increased non-cholinergic excitatory postsynaptic currents (EPSCs) in
      SubCD neurons, which were blocked by GLU receptor antagonists. Although no
      developmental changes were observed in the relative contribution of AMPA/KA and
      NMDA receptors to the responses, there was a developmental decrease in the half
      width duration of both evoked and miniature EPSCs. Bath application of NMDA or KA
      revealed a developmental decrease in the direct response of SubCD neurons to
      these agonists. CONCLUSIONS: The SubCD receives glutamatergic input, which may be
      involved in activation of SubCD neurons during REM sleep. A developmental
      decrease in the glutamatergic excitability of these neurons could underlie the
      developmental decrease in REM sleep observed in humans and rodents.

PMID- 22379248
TI  - Effect of short-term acclimatization to high altitude on sleep and nocturnal
      breathing.
AB  - STUDY OBJECTIVE: Objective physiologic data on sleep and nocturnal breathing at
      initial exposure and during acclimatization to high altitude are scant. We tested
      the hypothesis that acute exposure to high altitude induces quantitative and
      qualitative changes in sleep and that these changes are partially reversed with
      acclimatization. DESIGN: Prospective observation. SETTING: One night in a sleep
      laboratory at 490 meters, the first and the third night in a mountain hut at 4559
      meters. PARTICIPANTS: Sixteen healthy mountaineers. INTERVENTION: Altitude
      exposure. MEASUREMENTS: Polysomnography, questionnaire evaluation of sleep and
      acute mountain sickness. RESULTS: Compared to 490 m, median nocturnal oxygen
      saturation decreased during the 1st night at 4559 m from 96% to 67%, minute
      ventilation increased from 4.4 to 6.3 L/min, and the apnea-hypopnea index
      increased from 0.1 to 60.9/h; correspondingly, sleep efficiency decreased from
      93% to 69%, and slow wave sleep from 18% to 6% (P < 0.05, all instances). During
      the 3rd night at 4559 m, oxygen saturation was 71%, slow wave sleep 11% (P < 0.05
      vs. 1st night, both instances) and the apnea/hypopnea index was 86.5/h (P = NS
      vs. 1st night). Symptoms of AMS and of disturbed sleep were significantly reduced
      in the morning after the 3rd vs. the 1st night at 4559 m. CONCLUSIONS: In healthy
      mountaineers ascending rapidly to high altitude, sleep quality is initially
      impaired but improves with acclimatization in association with improved oxygen
      saturation, while periodic breathing persists. Therefore, high altitude sleep
      disturbances seem to be related predominantly to hypoxemia rather than to
      periodic breathing.

PMID- 22379249
TI  - AASM criteria for scoring respiratory events: interaction between apnea sensor
      and hypopnea definition.
AB  - STUDY OBJECTIVES: To examine the impact of using a nasal pressure sensor only vs
      the American Academy of Sleep Medicine (AASM) recommended combination of thermal
      and nasal pressure sensors on (1) the apnea index (AI), (2) the apnea-hypopnea
      index (AHI), where the AHI is calculated using both AASM definitions of hypopnea,
      and (3) the accuracy of a diagnosis of obstructive sleep apnea (OSA). DESIGN:
      Retrospective review of previously scored in-laboratory polysomnography. SETTING:
      A tertiary-hospital clinical sleep laboratory. PATIENTS OR PARTICIPANTS: One
      hundred sixty-four consecutive adult patients with a potential diagnosis of OSA,
      who were examined during a 3-month period. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: Studies were scored with and without the use of the oronasal thermal
      sensor. AIs and AHIs, using the nasal pressure sensor alone (AI(np) and AHI(np)),
      were compared with those using both a thermal sensor for the detection of apnea
      and a nasal pressure transducer for the detection of hypopnea (AI(th) and
      AHI(th)). Comparisons were repeated using the AASM recommended (AASM(rec)) and
      alternative (AASM(alt)) hypopnea definitions. AI was significantly different when
      measured from the different sensors, with AI(np) being 51% higher on average.
      Using the AASM(rec) hypopnea definition, the mean AHI(np) was 15% larger than the
      AHI(th); with large interindividual differences and an estimated 9.8% of patients
      having a false-positive OSA diagnosis at a cutpoint of 15 events and 4.3% at 30
      events per hour. Using AASM(alt) hypopnea definition, the mean AHI(np) was 3%
      larger than the AHI(th), with estimated false-positive rates of 4.6% and 2.4%,
      respectively. The false-negative rate was negligible at 0.1% for both hypopnea
      definitions. CONCLUSIONS: This study demonstrates that using only a nasal
      pressure sensor for the detection of apnea resulted in higher values of AI and
      AHI than when the AASM recommended thermal sensor was added to detect apnea. When
      the AASM(alt) hypopnea definition was used, the differences in AHI and subsequent
      OSA diagnosis were small and less than when the AASM(rec) hypopnea definition was
      used. In situations in which a thermal sensor cannot be used, for example, in
      limited-channel diagnostic devices, the AHI obtained with a nasal pressure sensor
      alone differs less from the AHI obtained from a polysomnogram that includes a
      thermal sensor when the AASM(alt) definition rather than the AASM(rec) definition
      of hypopnea is used. Thus, diagnostic accuracy is impacted both by the absence of
      the thermal sensor and by the rules used to analyze the polysomnography.
      Furthermore, where the thermal sensor is unreliable for sections of a study, it
      is likely that use of the nasal pressure signal to detect apnea will have modest
      impact.

PMID- 22379250
TI  - Assessing REM sleep in mice using video data.
AB  - STUDY OBJECTIVES: Assessment of sleep and its substages in mice currently
      requires implantation of chronic electrodes for measurement of
      electroencephalogram (EEG) and electromyogram (EMG). This is not ideal for high
      throughput screening. To address this deficiency, we present a novel method based
      on digital video analysis. This methodology extends previous approaches that
      estimate sleep and wakefulness without EEG/EMG in order to now discriminate rapid
      eye movement (REM) from non-REM (NREM) sleep. DESIGN: Studies were conducted in 8
      male C57BL/6J mice. EEG/EMG were recorded for 24 hours and manually scored in 10
      second epochs. Mouse behavior was continuously recorded by digital video at 10
      frames/second. Six variables were extracted from the video for each 10-second
      epoch (i.e., intraepoch mean of velocity, aspect ratio, and area of the mouse and
      intraepoch standard deviation of the same variables) and used as inputs for our
      model. MEASUREMENTS AND RESULTS: We focus on estimating features of REM (i.e.,
      time spent in REM, number of bouts, and median bout length) as well as time spent
      in NREM and WAKE. We also consider the model's epoch-by-epoch scoring performance
      relative to several alternative approaches. Our model provides good estimates of
      these features across the day both when averaged across mice and in individual
      mice, but the epoch-by-epoch agreement is not as good. CONCLUSIONS: There are
      subtle changes in the area and shape (i.e., aspect ratio) of the mouse as it
      transitions from NREM to REM, likely due to the atonia of REM, thus allowing our
      methodology to discriminate these two states. Although REM is relatively rare,
      our methodology can detect it and assess the amount of REM sleep.

PMID- 22379251
TI  - Low back pain: the time to become invested in clinical practice guidelines is
      now.

PMID- 22379252
TI  - Doctorate in physical therapy: is it time for a conversation?

PMID- 22379253
TI  - Prevention of fractures in older people: what does the evidence say?

PMID- 22379254
TI  - Managing a female patient with left low back pain and sacroiliac joint pain with
      therapeutic exercise: a case report.
AB  - PURPOSE: The purpose of this case study is to describe the management of a female
      patient with chronic left low back pain and sacroiliac joint pain (LBP/SIJP)
      using unique unilateral exercises developed by the Postural Restoration Institute
      (PRI) to address pelvic asymmetry and left hip capsule restriction, which is
      consistent with a Right Handed and Left Anterior Interior Chain pattern of
      postural asymmetry.Client Description: The client was 65-year-old woman with a 10
      month history of constant left LBP/SIJP and leg pain. INTERVENTION: The patient
      was seen six times to correct pelvic position/posture and left hip posterior
      capsule restriction via (1) muscle activation (left hamstrings, adductor magnus,
      and anterior gluteus medius) and (2) left hip adduction to lengthen the left
      posterior capsule/ischiofemoral ligament. Stabilization exercises included
      bilateral hamstrings, gluteus maximus, adductors, and abdominals to maintain
      pelvic position/posture.Measures and Outcome: Left Ober's test (initially
      positive) was negative at discharge. Pain as measured on the Numeric Pain Rating
      Scale (initially 1/10 at best and 8/10 at worst) was 0/10-0/10 at discharge.
      Oswestry Disability Index score (initially 20%) was 0% at discharge. The patient
      no longer had numbness in her left leg, and sexual intercourse had become pain
      free. IMPLICATIONS: INTERVENTIONs to restore and maintain the optimal position of
      pelvis and hip (femoral head in the acetabulum) may be beneficial for treating
      patients with chronic LBP/SIJP. The patient's pain was eliminated 13 days after
      she first performed three exercises to reposition the pelvis and restore left
      posterior hip capsule extensibility and internal rotation.

PMID- 22379255
TI  - Clinician's Commentary.

PMID- 22379257
TI  - Clinician's Commentary.

PMID- 22379256
TI  - Six-minute walk test for persons with mild or moderate disability from multiple
      sclerosis: performance and explanatory factors.
AB  - PURPOSE: The primary purpose of this study was to determine the extent to which
      health factors, functional measures, and pulmonary impairment explain performance
      on 6-Minute Walk Test (6MWT) distance in ambulatory persons with multiple
      sclerosis (MS). Another purpose was to determine the effect of disability and age
      on 6MWT performance and explanatory factors. METHODS: A cross-sectional study
      design was used to evaluate factors that explain performance on the 6MWT in 64
      community-dwelling persons with MS-related disability (Expanded Disability Status
      Scale [EDSS] 3.8+/-1.6). Of the 64 participants, 43 (67.2%) exhibited mild
      disability (EDSS <4.0) and 21 (32.8%) had moderate disability (EDSS 4.0-6.5). A
      regression analysis compared 6MWT performance to measures of health factors
      (EDSS, number of medications, number of comorbidities, resting HR, systolic and
      diastolic blood pressure [BP]); physical performance (functional stair test
      [FST], sit-to-stand test [SST], static standing balance [BAL], Fatigue Severity
      Scale [FSS], Activities-specific Balance Confidence [ABC] Scale); and pulmonary
      function (forced expiratory volume in 1 second [FEV(1)], forced vital capacity
      [FVC], maximal voluntary ventilation [MVV], maximal inspiratory pressure [MIP],
      maximal expiratory pressure [MEP]). RESULTS: EDSS, ABC, FST, SST, BAL, MVV, MIP,
      and MEP were significantly associated with 6MWT distance after adjusting for age.
      Multiple step-wise linear regression analysis revealed that ABC, FST, and BAL
      were significant and independent explanatory factors of 6MWT distance. ABC and
      FST explained 75% of the variance in 6MWT performance (R(2)=0.75). Curvilinear
      regression analysis revealed that the FST is the most significant explanatory
      factor for 6MWT distance, explaining 79% of the variance (R(2)=0.79).
      CONCLUSIONS: 6MWT performance in persons with MS was explained by balance
      confidence (ABC) and stair-climbing ability (FST). The ABC and FST may be
      practical clinical measures for explaining walking ability and determining risk
      for disablement in persons with MS.

PMID- 22379258
TI  - Your Pillow May Not Guarantee a Good Night's Sleep or Symptom-Free Waking.
AB  - PURPOSE: To describe the performance of the pillow that participants usually
      slept on with respect to retiring and waking cervico-thoracic symptoms, pillow
      comfort, and sleep quality. METHODS: Participants (n=106) were systematically
      recruited for a field trial comparing their own pillow and five trial pillows.
      Participants provided daily retiring and waking symptom reports and sleep-quality
      and pillow-comfort ratings prospectively for 1 week on each pillow. Linear and
      logistic regression models were used to investigate the relationship between
      pillow use, age, gender, sleep quality, pillow comfort, and waking and temporal
      (overnight) symptom reports. RESULTS: No waking symptoms were reported by 42.5%
      of participants on their own pillow. Regular waking symptoms, failure to relieve
      retiring symptoms, uncomfortable pillows, and/or poor-quality sleep were reported
      by over 50% of participants. All participants who reported poor sleep quality
      also reported poor pillow comfort. Pillow-comfort reports were not related to any
      waking symptom report; however, reports of poor sleep quality were significantly
      related to waking cervical stiffness (adjusted odds ratio [AOR]=4.3 [Confidence
      Interval (CI): 1.3-15.6]) and scapula pain (AOR=6.1 [CI: 1.1-31.6]). Feather
      pillow users provided consistently low reports of pillow comfort and sleep
      quality. CONCLUSION: Many participants appear to have made poor pillow choices,
      as poor sleep quality, low pillow comfort, and waking symptoms were common.
      Further research is required to understand why people choose particular pillows
      to sleep on, as well as to identify the best fit between person and pillow to
      optimize sleep quality and reduce waking symptoms.

PMID- 22379259
TI  - Physical therapy management of ventilated patients with acute respiratory
      distress syndrome or severe acute lung injury.

PMID- 22379260
TI  - Measuring Balance and Mobility after Traumatic Brain Injury: Validation of the
      Community Balance and Mobility Scale (CB&M).
AB  - PURPOSE: To further investigate the construct validity of the Community Balance
      and Mobility Scale (CB&M), developed for ambulatory individuals with traumatic
      brain injury (TBI). METHODS: A convenience sample of 35 patients with TBI (13 in
      patients, 22 outpatients) was recruited. Analyses included a comparison of CB&M
      and Berg Balance Scale (BBS) admission and change scores and associations between
      the CB&M and measures of postural sway, gait, and dynamic stability; the
      Community Integration Questionnaire (CIQ); and the Activities-specific Balance
      Confidence (ABC) Scale. RESULTS: Mean admission scores on the BBS and the CB&M
      were 53.6/56 (SD=4.3) and 57.8/96 (SD=23.3) respectively. Significant
      correlations were demonstrated between the CB&M and spatiotemporal measures of
      gait, including walking velocity, step length, step width, and step time;
      measures of dynamic stability, including variability in step length and step
      time; and the ABC (p<0.05). Significant correlations between the CB&M and CIQ
      were revealed with a larger data set (n=47 outpatients) combined from previous
      phases of research. CONCLUSIONS: In patients with TBI, the CB&M is less
      susceptible to a ceiling effect than the BBS. The construct validity of the CB&M
      was supported, demonstrating associations with laboratory measures of dynamic
      stability, measures of community integration, and balance confidence.

PMID- 22379261
TI  - Clinician's Commentary.

PMID- 22379262
TI  - Client Education: Communicative Interaction between Physiotherapists and Clients
      with Subacute Low Back Pain in Private Practice.
AB  - PURPOSE: To explore, through focus-group interviews, client education provided by
      physiotherapists in private practice who treat injured workers with subacute low
      back pain (SA-LBP). METHODS: Six focus-group interviews were held in the fall of
      2006 to explore treatment practices of physiotherapists for this population. Each
      of the 44 physiotherapists who volunteered attended one of six regional sessions.
      RESULTS: Three overarching themes emerged: the critical importance of education;
      education: a multidimensional concept; and the physiotherapist-client
      relationship. In this study, we found that education provides continuity by tying
      together the separate tasks occurring during one treatment session. Our
      participants said that time is of the essence in private practice and described
      how they provide education seamlessly, making this type of delivery efficient.
      CONCLUSIONS: Education is a highly valued aspect of practice for
      physiotherapists. Verbal, tactile, and visual information obtained from the
      client as assessment and treatment progress is explored, expanded, and
      contextualized in conversation with the client. In a communicative, interactive
      process, client fears, other contextual information, and physiotherapist
      information about procedures and techniques, exercises, and anatomy are
      collaboratively interrelated.

PMID- 22379264
TI  - Perceptions of physiotherapy best practice in total knee arthroplasty in hospital
      outpatient settings.
AB  - PURPOSE: The primary purpose of this study was to examine experienced
      physiotherapists' perceptions of best practices for patients following total knee
      arthroplasty (TKA) in publicly funded outpatient hospital settings in the Greater
      Toronto Area (GTA). The secondary objective was to identify the facilitators of
      and barriers to implementing best practices in the subacute phase of
      rehabilitation. METHODS: A qualitative, descriptive, focused ethnographic
      approach was used to explore physiotherapists' perceptions of best practices for
      patients with TKA. In-depth semi-structured interviews were conducted with expert
      physiotherapists acting as key informants. A snowball sampling method was used to
      recruit physiotherapists in the GTA. Interviews were conducted in person by two
      of the investigators. RESULTS: Physiotherapists from seven acute-care hospitals
      in the GTA participated in the study. Analysis of the 140 pages of transcripts
      from the interviews with 10 physiotherapists revealed that participants perceived
      best practices as encompassing the adoption of a client-centred approach; inter
      professional collaboration; aggressive rehabilitation for patients who are
      unsuccessful in achieving their outcomes; the use of relevant outcome measures;
      and consideration of the impact of scarce resources on care. CONCLUSIONS: The
      findings of this study highlight physiotherapists' perceived best practices for
      patients with TKA and the unique contribution that hospital-based outpatient
      physiotherapy can make to patients' rehabilitation.

PMID- 22379263
TI  - "They put you on your toes": Physical Therapists' Perceived Benefits from and
      Barriers to Supervising Students in the Clinical Setting.
AB  - PURPOSE: To identify the perceived benefits of and barriers to clinical
      supervision of physical therapy (PT) students. METHOD: In this qualitative
      descriptive study, three focus groups and six key-informant interviews were
      conducted with clinical physical therapists or administrators working in acute
      care, orthopaedic rehabilitation, or complex continuing care. Data were coded and
      analyzed for common ideas using a constant comparison approach. RESULTS:
      Perceived barriers to supervising students tended to be extrinsic: time and space
      constraints, challenging or difficult students, and decreased autonomy or
      flexibility for the clinical physical therapists. Benefits tended to be
      intrinsic: teaching provided personal gratification by promoting reflective
      practice and exposing clinical educators to current knowledge. The culture of
      different health care institutions was an important factor in therapists'
      perceptions of student supervision. CONCLUSIONS: Despite different disciplines
      and models of supervision, there is considerable synchronicity in the issues
      reported by physical therapists and other disciplines. Embedding the value of
      clinical teaching in the institution, along with strong communication links among
      academic partners, institutions, and potential clinical faculty, may mitigate
      barriers and increase the commitment and satisfaction of teaching staff.

PMID- 22379265
TI  - [Not Available].
AB  - INTRODUCTION: The Rehabilitation Network of Ottawa-Carleton (RENOC) recommends
      that its institutions use the Lower Extremity Functional Scale (LEFS). Since
      RENOC serves both Francophone and Anglophone clients, the LEFS needed to be
      translated to assess the Francophone clientele. OBJECTIVE: To create a French
      Canadian version of the LEFS, with the proposed title "Echelle fonctionnelle des
      membres inferieurs" (EFMI), and to examine its content validity. METHODOLOGY: A
      modified version of Vallerand's (1989) cross-validation technique for
      questionnaires was used to validate the equivalence of the French version of the
      LEFS. First, a parallel reverse translation of the LEFS was completed. Second, a
      committee of experts examined the two drafts and created a first experimental
      version of the EFMI. Third, this version was evaluated by a second committee of
      experts. Following the comments received, a second experimental version was
      created. Fourth, 35 rehabilitation professionals evaluated the second
      experimental version of the EFMI on a scale of ambiguity and proposed final
      changes. RESULTS: On the final version of the EFMI, the statements demonstrated a
      relatively low average level of ambiguity, ranging between 1 and 2.54.
      CONCLUSION: The rigorous four-step process followed in this study produced a
      French-Canadian version of the LEFS with demonstrated content validity.

PMID- 22379266
TI  - [Not Available].
AB  - INTRODUCTION: The Lower Extremity Functional Scale was translated into Canadian
      French in 2006; the translated version was titled Echelle fonctionnelle des
      membres inferieurs (EFMI). The construct validity and reliability of the EFMI
      have not been examined. OBJECTIVE: To examine the test-retest reliability,
      internal consistency, and construct validity of the EFMI. METHODOLOGY: Thirty
      four participants who had undergone surgery or had an injury to the lower limb
      were asked to fill out a demographic questionnaire and complete the EFMI after
      their initial assessment while hospitalized. They completed the EFMI a second
      time within 72 hours. The intra-class correlation coefficient (ICC) and the kappa
      coefficient were chosen to examine the test-retest reliability of the EFMI, and
      Cronbach's alpha coefficient was calculated to assess internal consistency. A
      factor analysis was conducted to examine construct validity by determining the
      number of constructs and their meanings. RESULTS: The ICC value was 0.92 (95% CI:
      0.88-0.96), and Cronbach's alpha was 0.95 (95% CI: 0.91-0.99). The factor
      analysis revealed that all elements of the EFMI share one principal construct.
      CONCLUSION: The results demonstrate that the French-Canadian version of the EFMI
      is a unidimensional tool with excellent test-retest reliability.

PMID- 22379267
TI  - What Does the Cochrane Collaboration Say about Organization of Care?

PMID- 22379269
TI  - Two-Type Reducible Age-Dependent Branching Processes With Non-Homogeneous Poisson
      Immigration.
AB  - Two type reducible age-dependent branching stochastic processes with non
      homogeneous Poisson immigration are considered as models of renewal cell
      population dynamics. The asymptotic behaviour of the first moments of the process
      with or without immigration is investigated. Several classes of asymptotic
      behavior are identified for the population dynamics. Our results are also useful
      for developing associated methods of statistical inference.

PMID- 22379270
TI  - The right thing to do.

PMID- 22379271
TI  - Endovascular management of acute upper extremity deep venous thrombosis and the
      use of superior vena cava filters.
AB  - Upper extremity deep venous thrombosis (UEDVT), though less common than lower
      extremity DVT, is a significant problem with several possible etiologies. The
      incidence of UEDVT is on the rise, primarily from the increasing use of central
      venous access devices. However, there are other causes of UEDVT, including
      primary venous thrombosis (Paget-Schroetter syndrome) and hypercoagulable states
      associated with underlying malignancy. The morbidity and mortality associated
      with UEDVT is largely from pulmonary embolism and the postphlebitic syndrome.
      Nevertheless, many UEDVTs are asymptomatic or patients may present with
      nonspecific clinical symptoms; therefore, a high index of suspicion is often
      necessary to make a correct diagnosis. Currently, there is no standard treatment
      algorithm for UEDVT. Treatment options may range from systemic anticoagulation to
      surgical correction depending on the etiology of the thrombus, as well as the
      patient's associated comorbidities, life expectancy and expected quality of life
      following treatment.

PMID- 22379273
TI  - Management of pulmonary arteriovenous malformations.
AB  - Pulmonary arteriovenous malformations are rare lesions with significant clinical
      complications. These lesions are commonly seen in patients with hereditary
      hemorrhagic telangiectasia (formerly Osler-Weber-Rendu syndrome). Interventional
      radiologists are a key part of the treatment team in this complex disease, and a
      thorough understanding of the disease process is critical to providing good
      patient care. In this article, the authors review the disease course and its
      association with hereditary hemorrhagic telangiectasia, discusses the clinical
      evaluation and treatment of these complex patients, and outlines complications
      and follow-up.

PMID- 22379272
TI  - Endovascular management of acute aortic syndromes.
AB  - The term "acute aortic syndrome" (AAS) refers to a spectrum of life-threatening
      thoracic aortic pathologies including intramural hematoma, penetrating
      atherosclerotic ulcer, and aortic dissection. Clinically, patients often present
      with characteristic aortic pain. AAS often leads to aortic rupture. Therefore,
      recognition of this condition, its prompt diagnosis, and timely treatment is
      crucial to obtain clinical success and improved overall survival. The management
      of AAS, however, remains a therapeutic challenge. Endovascular strategies have
      gained wide acceptance and now represent a minimally invasive alternative to
      traditional open surgery. Several studies have shown endovascular repair of
      varying thoracic aortic pathologies to be technically feasible with fewer
      complications than open surgery. In this review, the authors discuss AAS
      pathology and its management, with particular attention to the current role of
      endovascular aortic repair and its treatment.

PMID- 22379274
TI  - Endovascular management of chronic upper extremity deep vein thrombosis and
      superior vena cava syndrome.
AB  - Chronic upper extremity deep vein thrombosis (UEDVT) and superior vena cava
      syndrome (SVCS) are important and underdiagnosed entities that are associated
      with significant morbidity, and both are becoming increasingly common due to the
      use of indwelling catheters and implantable central venous access devices.
      Currently, as many as 25% of patients with an indwelling catheter are diagnosed
      with chronic UEDVT or venous stenosis. SVCS is most commonly seen in the setting
      of malignancy, especially lung cancer and lymphoma. Endovascular management of
      chronic UEDVT and SVCS is accepted as an important first-line treatment given its
      high overall success rate and low morbidity as compared with medical and surgical
      treatments. In this article, the indications for treatment, complications, and
      success rates of the endovascular management of UEDVT and SVCS are reviewed.
      Relevant findings on presentation and physical exam as well as various imaging
      modalities and imaging findings are evaluated. Details of preprocedure
      evaluation, relevant anatomy, and avoidance of potential complications are
      discussed.

PMID- 22379275
TI  - Tube thoracostomy: a review for the interventional radiologist.
AB  - Small-caliber tube thoracostomy is a valuable treatment for various pathologic
      conditions of the pleural space. Smaller caliber tubes placed under image
      guidance are becoming increasingly useful in numerous situations, are less
      painful than larger surgical tubes, and provide more accurate positioning when
      compared with tubes placed without image guidance. Basic anatomy and physiology
      of the pleural space, indications, and contraindications of small caliber tube
      thoracostomy, techniques for image-guided placement, complications and management
      of tube thoracostomy, and fundamental principles of pleurodesis are discussed in
      this review.

PMID- 22379276
TI  - Bronchial artery embolization for hemoptysis.
AB  - Bronchial artery angiography with embolization has become a mainstay in the
      treatment of hemoptysis. Major complications are rare and immediate clinical
      success defined as cessation of hemorrhage ranges in most series from 85% to
      100%, although recurrence of hemorrhage ranges from 10% to 33%. Bronchial artery
      embolization offers a minimally invasive procedure for even the most compromised
      patient serving as first-line treatment for hemorrhage as well as providing a
      bridge to more definitive medical or surgical intervention focused upon the
      etiology of the hemorrhage. The aim of this article is to summarize the
      etiologies, pathophysiology, and the diagnostic and management strategies of
      hemoptysis as related to bronchial artery embolization. In addition, the
      techniques of arteriography and embolization as well as associated procedural
      outcomes and complications are delineated.

PMID- 22379277
TI  - Thoracic duct embolization for chylous leaks.
AB  - Chylous leaks, such as chylothorax and chylopericardium, are uncommon effusions
      resulting from the leakage of intestinal lymphatic fluid from the thoracic duct
      (TD) and its tributaries, or intestinal lymphatic ducts. The cause can be either
      traumatic (thoracic surgery) or nontraumatic (idiopathic, malignancy). Treatment
      has traditionally consisted of dietary modification (nonfat diet) and/or surgery
      (TD ligation, pleurodesis). Thoracic duct embolization (TDE) has become a viable
      treatment alternative due to it high success rate and minimal complications. In
      this article, the authors describe the etiologies of chylothorax, patient
      population, outcomes, and long-term follow-up of TDE patients. Relevant lymphatic
      anatomy and physiology are reviewed, with special attention paid to the formation
      of the duct by tributaries at the cisterna chyli (CC). The technique of TDE is
      outlined, including bilateral pedal lymphangiography, TD cannulation, and embolic
      agents used for the procedure.

PMID- 22379278
TI  - Management of pleural effusion, empyema, and lung abscess.
AB  - Pleural effusion is an accumulation of fluid in the pleural space that is
      classified as transudate or exudate according to its composition and underlying
      pathophysiology. Empyema is defined by purulent fluid collection in the pleural
      space, which is most commonly caused by pneumonia. A lung abscess, on the other
      hand, is a parenchymal necrosis with confined cavitation that results from a
      pulmonary infection. Pleural effusion, empyema, and lung abscess are commonly
      encountered clinical problems that increase mortality. These conditions have
      traditionally been managed by antibiotics or surgical placement of a large
      drainage tube. However, as the efficacy of minimally invasive interventional
      procedures has been well established, image-guided small percutaneous drainage
      tubes have been considered as the mainstay of treatment for patients with pleural
      fluid collections or a lung abscess. In this article, the technical aspects of
      image-guided interventions, indications, expected benefits, and complications are
      discussed and the published literature is reviewed.

PMID- 22379279
TI  - Transthoracic needle biopsy.
AB  - Transthoracic needle biopsy (TTNB) is integral in the diagnosis and treatment of
      many thoracic diseases, and is an important alternative to more invasive surgical
      procedures. Both computed tomography and ultrasound may be used as imaging
      guidance for TTNB, with CT being more commonly utilized. Needle choice depends
      mostly upon lesion characteristics and location. During the procedure, patients
      must be able to follow breathing instructions. Common complications of TTNB
      include pneumothorax and hemoptysis.

PMID- 22379280
TI  - Endovascular stent grafts in urgent blunt and penetrating thoracic aortic trauma.
AB  - A traumatic thoracic aortic injury is fatal in the majority of cases. Surviving
      the aortic injury in addition to the myriad of associated trauma requires
      comprehensive medical management from many medical services. Balancing these
      services and coordinating the medical care requires free and open communication
      between services. Although one might assume a thoracic aortic injury takes
      precedence over other injuries, an organized plan of care in which the morbidity
      of the injury as well as the consequences of treatment of each injury helps
      provide an appropriate "rank order" in the treatment process. A patient with a
      thoracic aortic injury can be observed for several days while additional injuries
      are treated, as long as appropriate blood pressure controls are observed. The
      treatment order for multiple injuries must be reevaluated on a regular basis to
      adjust for changes in the overall clinical condition. This rank order to
      treatment and scheduled treatment plan allows for appropriate imaging,
      evaluation, and coordination of services in preparation for the placement of a
      thoracic aortic stent graft. The goal of treatment is to reduce the risk of
      aortic rupture and subsequent fatal hemorrhage. Choosing an open surgical repair
      versus an endovascular stent graft depends upon physician expertise and clinical
      status of the patient. In the appropriate clinical setting, endovascular repair
      of the thoracic aortic injury has become the treatment of choice at the authors'
      institution in patients with significant operative risks and extensive comorbid
      injuries. Specific characteristics of the injured aorta also dictate the type of
      endovascular device required for repair. Case reviews of a patient with blunt
      trauma and a patient with penetrating trauma used to demonstrate clinical
      parameters, imaging options, and details of stent graft choice and placement, are
      presented followed by a review of the literature.

PMID- 22379281
TI  - Endovascular repair of thoracic aortic aneurysms.
AB  - Degenerative aneurysms of the thoracic aorta are increasing in prevalence; open
      repair of descending thoracic aortic aneurysms is associated with high rates of
      morbidity and mortality. Repair of isolated descending thoracic aortic aneurysms
      using stent grafts was introduced in 1995, and in an anatomically suitable
      subgroup of patients with thoracic aortic aneurysm, repair with endovascular
      stent graft provides favorable outcomes, with decreased perioperative morbidity
      and mortality relative to open repair. The cornerstones of successful thoracic
      endovascular aneurysm repair are appropriate patient selection, thorough
      preprocedural planning, and cautious procedural execution, the elements of which
      are discussed here.

PMID- 22379282
TI  - Improving the tracking and removal of retrievable inferior vena cava filters.
AB  - Therapeutic and prophylactic inferior vena cava (IVC) filters should be placed
      based on currently accepted indications to prevent a fatal pulmonary embolism
      (PE). The protective effect of filters is offset by the potential for lower
      extremity deep venous thrombosis (DVT), caval thrombosis, and possible otherwise
      unnecessary life-long anticoagulation (AC). The duration of treatment for most
      DVTs or PEs is 3 to 6 months of AC/filter. Filters should be retrieved when
      duration of treatment for a DVT/PE has been met, the risk of a PE is no longer
      high, and/or there is no longer a contraindication to AC. An effective system
      that leads to improving the retrieval rate of filters must include education of
      the patient, a tracking system to minimize patient lost to follow-up, and
      dedicated personnel to oversee the process. If these goals are accomplished,
      interventionalists can help decrease the incidence of a fatal PE during the high
      risk period, and also decrease the risk of a DVT or the use of otherwise
      unnecessary life-long AC in subsequent years. Currently, there is much room for
      improvement in the frequency that IVCF patients are systematically followed and
      filters are retrieved. The principles discussed in this report will be helpful in
      this process.

PMID- 22379283
TI  - Covered stent compression in dialysis access.

PMID- 22379284
TI  - Coupling Time Decoding and Trajectory Decoding using a Target-Included Model in
      the Motor Cortex.
AB  - Significant progress has been made within the last decade in motor cortical
      decoding that predicts movement behaviors from population neuronal activity in
      the motor cortex. A majority of these decoding methods have focused on estimating
      a subject's hand trajectory in a continuous movement. We recently proposed a time
      identification decoding approach and showed that if a stereotyped movement is
      well represented by a sequence of targets (or landmarks), then the main structure
      of the movement can be reconstructed by detecting the reaching times at those
      targets. Both trajectory decoding and landmark-time decoding have their
      particular advantages, whereas a coupling of these two different strategies has
      not been examined. In this article we propose a synergy that comes from combining
      these two approaches for a stereotyped movement under a linear state-space
      framework. We develop a new decoding procedure based on a forward-backward
      propagation where the target is used in the initial stage in the backward step.
      Experimental results show that the new method significantly improves decoding
      accuracy over the non-target-included models. Furthermore, the coupling based on
      the new target-included method effectively combines the time decoding and
      trajectory decoding and further improves the decoding accuracy.

PMID- 22379285
TI  - Effect of multimodal coupling in imaging micro-endoscopic fiber bundle on optical
      coherence tomography.
AB  - The effect of higher order modes in fiber bundle imager-based optical coherence
      tomography (OCT) has been theoretically modeled using coupled fiber mode analysis
      ignoring the polarization and core size variation in order to visualize the pure
      effect of multimodal coupling of the imaging bundle. In this model, the optical
      imaging fiber couples several higher order modes in addition to the fundamental
      one due to its high numerical aperture for achieving light confinement to the
      single core pixel. Those modes become evident in a distance domain using A-mode
      (depth) OCT based on a mirror sample experiment where multiple peaks are
      generated by the spatial convolution and coherence function of the light source.
      The distance between the peaks corresponding to each mode can be estimated by
      considering the effective indices of coupled (guided) modes obtained from
      numerically solving the fiber mode characteristics equations and the fiber
      length. The results have been compared for various types (fiber dimensions and
      wavelengths) and lengths of fibers, which have mode separation of 715 MUm (1404
      MUm) and 764 MUm (1527 MUm) for the measurement and analysis, respectively in a
      152.5 mm (305 mm)-long imaging fiber.

PMID- 22379286
TI  - Querying Event Sequences by Exact Match or Similarity Search: Design and
      Empirical Evaluation.
AB  - Specifying event sequence queries is challenging even for skilled computer
      professionals familiar with SQL. Most graphical user interfaces for database
      search use an exact match approach, which is often effective, but near misses may
      also be of interest. We describe a new similarity search interface, in which
      users specify a query by simply placing events on a blank timeline and retrieve a
      similarity-ranked list of results. Behind this user interface is a new similarity
      measure for event sequences which the users can customize by four decision
      criteria, enabling them to adjust the impact of missing, extra, or swapped events
      or the impact of time shifts. We describe a use case with Electronic Health
      Records based on our ongoing collaboration with hospital physicians. A controlled
      experiment with 18 participants compared exact match and similarity search
      interfaces. We report on the advantages and disadvantages of each interface and
      suggest a hybrid interface combining the best of both.

PMID- 22379287
TI  - Seroprevalence and trends in transfusion transmitted infections among blood
      donors in a university hospital blood bank: a 5 year study.
AB  - Blood is life. Transfusion of blood and blood components, as a specialized
      modality of patient management saves millions of lives worldwide each year and
      reduce morbidity. It is well known that blood transfusion is associated with a
      large number of complications, some are only trivial and others are potentially
      life threatening, demanding for meticulous pretransfusion testing and screening
      particularly for transfusion transmissible infections (TTI). These TTI are a
      threat to blood safety. The priority objective of BTS is thus to ensure safety,
      adequacy, accessibility and efficiency of blood supply at all levels. The
      objective of the present study was to assess the prevalence and trend of
      transfusion transmitted infections (TTI) among voluntary and replacement donors
      in the Department of Blood bank and transfusion Medicine of JSS College Hospital,
      a teaching hospital of Mysore during the period from 2004 to 2008. A
      retrospective review of donors record covering the period between 2004 and 2008
      at the blood bank, JSS Hospital, Mysore was carried out. All samples were
      screened for HIV, HBsAg, HCV, syphilis and malaria. Of the 39,060, 25,303
      (64.78%) were voluntary donors and the remaining 13,757 (35.22%) were replacement
      donors. The overall prevalence of HIV, HbsAg, HCV and syphilis were 0.44, 1.27,
      0.23 and 0.28%, respectively. No blood donor tested showed positivity for
      malarial parasite. Majority were voluntary donors with male preponderance. In all
      the markers tested there was increased prevalence of TTI among the replacement
      donors as compared to voluntary donors. With the implementation of strict donor
      criteria and use of sensitive screening tests, it may be possible to reduce the
      incidence of TTI in the Indian scenario.

PMID- 22379288
TI  - Total Leukocyte Counts and the Requirement of Dose Reduction due to Cytopenias as
      Prognostic Indicators Affecting Response to Imatinib in Chronic Myeloid Leukemia.
AB  - Imatinib is a tyrosine kinase inhibitor and is considered the first line of non
      stem cell transplantation treatment for patients diagnosed with CML. We evaluated
      the response rates and adverse reactions to Imatinib in our patients and tried to
      identify factors which affected the response to Imatinib. Eighty-four patients
      were diagnosed on the basis of clinical and haematological variables with
      confirmation by FISH, detecting Philadelphia chromosome or bcr-abl translocation
      and were then started on oral capsule Imatinib. A complete haematological
      response was seen in 78.04% patients, while complete cytogenetic response (CCR)
      was seen in 12.2% of patients and major cytogenetic response (MCR) was seen in
      64.63% of patients. It was found that that a greater total leukocyte count (TLC)
      on presentation had a negative correlation with cytogenetic response. Cytopenias
      were seen in 36 patients (43.82%). 34.9% of patients having CCR/MCR required dose
      reduction while 73.6% of patients not achieving CCR/MCR required dose reduction.
      This was a significant difference, confirmed on statistical analysis (P < 0.05; P
      = 0.019), establishing the negative prognostic value of dose reduction due to
      cytopenias.

PMID- 22379289
TI  - Significance of Hematological Scoring System (HSS) in Early Diagnosis of Neonatal
      Sepsis.
AB  - Neonates are easily prone for bacterial infection. Diagnosis of neonatal
      septicemia may be difficult as the early signs of sepsis may be subtle and
      different at different gestational ages. The present study was undertaken to
      assess the significance of the hematological scoring system (HSS) for early
      detection of neonatal sepsis. About 50 peripheral blood smears of all newborns
      collected were analysed for neonatal sepsis using the HSS of Rodwell et al. (J
      Pediatr 112:761-767, 1988). Analysis in our study found that an abnormal immature
      to total neutrophil ratio (I:T) followed by an abnormal immature to mature
      neutrophil ratio (I:M) were the most sensitive indicators in identifying infants
      with sepsis. The HSS is a simple, quick, cost effective tool which can be used as
      a screening test for early diagnosis of neonatal sepsis.

PMID- 22379290
TI  - Prognostic significance of survivin in pediatric acute lymphoblastic leukemia.
AB  - Impaired apoptosis is mediated by members of the inhibitor of apoptosis proteins
      (IAP) family such as survivin. Survivin was described in number of different
      tumors and found to correlate with poor prognosis in a variety of cancers
      including hematologic malignancies. The aim of this study was to determine
      survivin in pediatric ALL and compare it with clinical and hematological
      findings, response to therapy and outcome. Flowcytometry was used for detection
      of intracellular survivin and determine its mean fluorescence intensity (MFI) in
      bone marrow mononuclear cells. Patients were followed up for 28 months after
      induction therapy. Survivin was detected in 63.3% of the patients BM. In spite of
      no association of survivin levels with established risk factors (P > 0.05) except
      with high WBC, there was significant higher level of survivin expression in high
      risk group patients when patients were stratified into high and standard risk
      groups. According to response to induction therapy, there was no significant
      difference, in survivin level between patients who achieved CR, RD and ED.
      However, patients suffering relapse of the disease, had a significant higher
      basal level of survivin than patients still in remission. Over expression of
      survivin is a candidate parameter to determine poor prognosis in ALL patients and
      it may serve to refine treatment stratification with intensification of therapy
      in those patients prone to relapse.

PMID- 22379291
TI  - Characteristics of anemia in elderly: a hospital based study in South India.
AB  - Anemia is a common concern in older people and can have significant morbidity and
      mortality. Because anemia is a sign, not a diagnosis, an evaluation is almost
      always warranted to identify the underlying cause. The purpose of this study was
      to study the clinical profile of elderly patients with anemia and to study
      characteristics of hematological types of anemia in such patients as well as the
      closest possible etiological profile. Hundred patients above the age of 60 years
      were included in the study. Clinical profile with laboratory studies of
      Hemoglobin and diagnostic tests to fix the etiology. Majority of patients had
      normocytic blood picture. Renal failure was the most common underlying chronic
      disease. Significant number of patients were on non steroidal anti-inflammatory
      drugs which could contribute to the anaemia. 14% of the patients had an
      underlying malignancy. 73.3% of the patients in the microcytic group had an
      underlying GI lesion on endoscopy. Identifying anemia as an important aspect of a
      comprehensive geriatric assessment is absolutely essential further to clinical
      detection. Confirming the type of anemia is critical to direct the investigation
      for profiling the etiology since it is well known that the treatment of anemia
      goes a long way in improving the overall outcome and quality of life.

PMID- 22379292
TI  - Simultaneous presence of two hematological malignancies: chronic lymphocytic
      leukemia and myelofibrosis in a patient.
AB  - Coexistence of chronic lymphocytic leukemia (CLL) with myelofibrosis is a rare
      association with only isolated case reports in the literature. We report an
      unusual case of CLL in which the cause of anemia was coexistent myelofibrosis. In
      a case of CLL presenting with refractory anemia, besides common causes like
      autoimmune hemolytic anemia and marrow infiltration, other causes like
      myelofibrosis should be searched for.

PMID- 22379293
TI  - A Case of HIV Infection with Thrombocytopenia: Assosiation of HIV, Thrombotic
      Thrombocytopenic Purpura and Brucellosis.
AB  - To report a case of HIV infection presenting with thrombotic thrombocytopenic
      purpura (TTP) and brucellosis that responded well to plasmapheresis and anti
      infective therapy. A 64-year-old woman with moderate confusion, fever and
      pancytopenia was admitted. HIV infection history was taken from her family and
      she was not receiving antiretroviral therapy last one year. She had generalized
      purpuric skin lesions. Wright tube agglutination test was found positive with a
      1:160 dilution and the patient was diagnosed as brucellosis. Detailed literature
      search showed brucellosis as a possible cause of TTP. Patient was treated by
      plasma exchange/fresh frozen plasma and antimicrobials and the response was
      excellent. Although brucellosis seems to explain the clinical picture of this
      patient, it is revealed that broad differential diagnosis is needed to reach
      uncommon diagnosis like TTP particularly in HIV infected patients.

PMID- 22379294
TI  - Hepatosplenic T-cell lymphoma.
AB  - We report an uncommon case of 38-year-old male patient with Hepatosplenic T-Cell
      lymphoma (HSTCL) which is a rare aggressive form of Peripheral T-Cell lymphoma
      that is characterized by primary extranodal disease with malignant T-cell
      proliferation in the liver, spleen, and bone marrow. Our patient presented with
      progressive painless jaundice, weight loss and massive hepatosplenomegaly. The
      diagnosis was challenging as he required an extensive investigations that
      ultimately showed the characteristic clinical, histopathologic, and cytogenetic
      features of hepatosplenic T-cell lymphoma.

PMID- 22379295
TI  - Rare presentation of pediatric acute lymphoblastic leukemia: nephromegaly at time
      of diagnosis.
AB  - Renal involvement is a fairly frequent development in children with acute
      lymphoblastic leukemia, but palpable renal enlargement at time of diagnosis is
      very unusual. We report the case of a young girl who presented with enlarged
      kidneys and was diagnosed with this form of leukemia. This case is of interest
      because of the rarity of this presentation. The importance of renal biopsy in
      identifying the etiology of this patient's nephromegaly is emphasized.

PMID- 22379296
TI  - Mycoplasma pneumonia Infection: A Possible Trigger for Immune Thrombocytopenia.
AB  - Mycoplasma pneumonia (M. pneumonia) is usually not considered among the several
      pathogens that induce immune thrombocytopenia (ITP). We report a child with a
      clinical diagnosis of severe ITP that was associated with M. pneumonia pneumonia,
      and review the few cases described in the English literature. We suggest that
      thrombocytopenia associated with M. pneumonia infection may constitute a subset
      of ITP, although unlike ITP it occurs concomitantly with the infection and tends
      to be more severe than "classic" ITP. We recommend that prompt specific
      antibiotic and immune modulating treatment should be initiated in appropriate
      clinical settings.

PMID- 22379297
TI  - Central nervous system blast crisis in chronic myeloid leukemia on imatinib
      mesylate therapy: report of two cases.
AB  - Chronic myeloid leukaemia is a chronic myeloproliferative disorder characterised
      by a reciprocal translocation between chromosomes 9 and 22 and thereby formation
      of the Philadelphia chromosome. Imatinib mesylate (STI-571) is a potent and
      selective inhibitor of BCR-ABL tyrosine kinase and has emerged as a treatment of
      choice in chronic myeloid leukaemia (CML) patients in chronic phase. It has shown
      activity in CML patients in the chronic phase or blastic phase. However there is
      poor penetration of the central nervous system (CNS) by the drug or its active
      metabolites. Therefore the CNS acts as a sanctuary site for malignant cells for
      CML patients treated with Imatinib. We report cases of two CML patients on
      Imatinib therapy, who were in haematological remission but developed CNS disease.

PMID- 22379298
TI  - Nanodentistry: A Paradigm Shift-from Fiction to Reality.
AB  - Nanodentistry is an emerging field with significant potential to yield new
      generation of technologically advanced clinical tools and devices for oral
      healthcare. Nanoscale topology and quantitative biomechanical or biophysical
      analysis of dental surfaces are of significant interest. In particular, using
      Atomic force microscopy techniques-diseases such as dental caries, tooth
      hypersensitivity, and oral cancer can be quantified based on morphological,
      biophysical and biochemical nanoscale properties of tooth surface itself and
      dental materials or oral fluids such as saliva. An outlook on future
      "nanodentistry" developments such as saliva exosomes based diagnostics, designing
      biocompatible, antimicrobial dental implants and personalized dental healthcare
      is presented. This article examines current applications of nanotechnology
      alongside proposed applications in the future and aims to demonstrate that, as
      well as a good deal of science fiction, there is some tangible science fact
      emerging from this novel multidisciplinary science.

PMID- 22379299
TI  - The science of anterior teeth selection for a completely edentulous patient: a
      literature review.
AB  - Esthetic replacement and physiological tooth arrangement made the complete
      denture biologically compatible and desirable. Proper placement of tooth should
      be functional and esthetically pleasing to enhance the psychology of the patient.
      This article reviews the evolution of concepts for teeth selection and the recent
      techniques employed for selecting anterior teeth for complete dentures.

PMID- 22379300
TI  - Evaluation and comparison of the effect of different surface preparations on bond
      strength of glass ionomer cement with nickel-chrome metal-ceramic alloy: a
      laboratory study.
AB  - Retention of fixed partial dentures is mostly dependent upon the bond between
      metal and cement as well as cement and tooth structure. However, most of the time
      clinical failure of bond has been observed at metal and cement interface. The
      treatment of metal surface, prior to luting, plays a crucial role in bonding
      cement with the metal. This study is conducted to evaluate and compare the effect
      of different surface preparations on the bond strength of resin-modified glass
      ionomer cement with nickel-chromium metal ceramic alloy. Fifty caries-free
      extracted molar teeth were made flat until the dentin of the occlusal surface was
      exposed. After fabrication of the wax patterns and subsequent castings, the
      castings were subjected to porcelain firing cycles. The nickel-chromium metal
      ceramic alloy discs were also divided into five groups and subjected to various
      surface treatments: (1) Unsandblasted (U), (2) sandblasted (S), (3) sandblasted
      and treated with 10% aqueous solution of KMnO4 (SK), (4) unsandblasted and
      roughened with diamond abrasive points (UD) and (5) unsandblasted and roughened
      with diamond abrasive points and treated with 10% aqueous solution of KMnO(4)
      (UDK). After surface treatments, the castings were cemented using Fuji PLUS
      encapsulated resin-modified glass ionomer cement. The obtained values of all the
      groups were subjected to statistical analysis for Tensile and Shear bond
      strength. Different surface treatments of the metal affects the bond strength
      values of resin-modified glass ionomer cement when used as luting agent.

PMID- 22379301
TI  - A Study on Effect of Surface Treatments on the Shear Bond Strength between
      Composite Resin and Acrylic Resin Denture Teeth.
AB  - Visible light-cured composite resins have become popular in prosthetic dentistry
      for the replacement of fractured/debonded denture teeth, making composite denture
      teeth on partial denture metal frameworks, esthetic modification of denture teeth
      to harmonize with the characteristics of adjacent natural teeth, remodelling of
      worn occlusal surfaces of posterior denture teeth etc. However, the researches
      published on the bond strength between VLC composite resins and acrylic resin
      denture teeth is very limited. The purpose of this study is to investigate the
      effect of five different methods of surface treatments on acrylic resin teeth on
      the shear bond strength between light activated composite resin and acrylic resin
      denture teeth. Ninety cylindrical sticks of acrylic resin with denture teeth
      mounted atop were prepared. Various treatments were done upon the acrylic resin
      teeth surfaces. The samples were divided into six groups, containing 15 samples
      each. Over all the treated and untreated surfaces of all groups, light-cured
      composite resin was applied. The shear strengths were measured in a Universal
      Testing Machine using a knife-edge shear test. Data were analyzed using one way
      analysis of variance (ANOVA) and mean values were compared by the F test.
      Application of bonding agent with prior treatment of methyl methacrylate on the
      acrylic resin denture teeth resulted in maximum bond strength with composite
      resin.

PMID- 22379302
TI  - Evaluation of dimensional stability, accuracy and surface hardness of
      interocclusal recording materials at various time intervals: an in vitro study.
AB  - To evaluate and compare the dimensional stability, accuracy and surface hardness
      of three interocclusal recording materials at various time intervals.
      Polyvinylsiloxane, Zinc oxide eugenol, Aluwax were taken for this study. A
      stainless steel die of ADA specification no 19. was prepared. A total of ten
      samples were made with each group. The samples were measured using a travelling
      microscope of 10* magnification at 1, 24, 48 and 72 h time intervals. Five
      readings were taken for each sample, the mean was considered to measure the
      dimensional change, accuracy and surface hardness. The values obtained were
      statistically analysed by ANOVA and Tukey HSD-Honestly significant difference.
      Polyvinylsiloxane was the most dimensionally stable, accurate and had the highest
      surface hardness among the three inter-occlusal materials.

PMID- 22379303
TI  - Cocktail Impression Technique: A New Approach to Atwood's Order VI Mandibular
      Ridge Deformity.
AB  - The management of highly resorbed ridge has always posed a challenge to the
      prosthodontist for years. Obtaining consistent mandibular denture stability has
      long been a challenge for dental profession. In particular, Atwood's Order V and
      Order VI pattern of bone resorption is associated with difficulties in providing
      successful dentures. Stability of lower denture in such cases is usually the
      distinguishing factor between success and failure. This article outlines a
      combination of different impression techniques to improve mandibular denture
      stability in an atrophic mandibular ridge, keeping in mind the prevention of
      further ridge resorption.

PMID- 22379304
TI  - Disinfecting the acrylic resin plate using electrolyzed acid water and 2%
      glutaraldehyde: a comparative microbiological study.
AB  - Marked bactericidal activity of the electrolyzed acid water (EAW) and its less
      undesirable effects on biological tissues and the environment has been
      successfully utilized in dental practice. A review of literature reveals that not
      many studies have been performed to determine the disinfection effect of EAW on
      heat cured acrylic denture bases. The objective of the study is to determine the
      efficacy of EAW in disinfecting heat cured acrylic resin specimens as compared to
      the efficacy of disinfecting the specimens using 2% glutaraldehyde. Heat cured
      acrylic resin plates were immersed in Bacteria suspensions of Staphylococcus
      aureus and later disinfected using EAW which was produced using a custom made
      electrolyzing apparatus and 2% glutaraldehyde for different time intervals. The
      numbers of surviving bacteria were counted. As the control, the bacteria attached
      on the specimens were counted with out any disinfection treatment. The results
      obtained were statistically analyzed using ANOVA and post-hoc test. The
      disinfection potential of 2% glutaraldehyde was better than EAW when the
      specimens were disinfected for 1 and 3 min. Where as when the disinfection time
      was increased to 5 min there was no difference between EAW and 2% glutaraldehyde.
      However considering that the disinfecting time can be easily extended to 5 min,
      EAW can be effectively used for disinfecting the acrylic denture.

PMID- 22379305
TI  - The effect of incorporation, orientation and silane treatment of glass fibers on
      the fracture resistance of interim fixed partial dentures.
AB  - Fracture of interim fixed partial dentures (FPD) is of important concern to the
      dental surgeon, especially with long-span fixed partial dentures or areas of
      heavy occlusal stress. Polymers used in interim FPDs, reinforced with glass
      fibers have shown to have a positive effect on the fracture resistance of interim
      FPDs. Since little research has been done on the influence of silane treated
      glass fibers on the fracture resistance of interim FPDs, this study was conducted
      to evaluate the effect of silane treatment of glass fibers on the fracture
      resistance of interim FPDs and its correlation with the position of fiber
      reinforcement and length of the span of the interim FPD. Interim FPDs were
      fabricated from an autopolymerizing polymethyl methacrylate (PMMA) resin. Seven
      FPDs were made in each group. The FPDs in the control group were unreinforced,
      and in the other groups the FPDs were reinforced either with non silane treated
      glass fiber or with silane treated glass fiber. The fibers were placed in two
      different locations in the FPDs. Three length of span of FPDs were tested. The
      load was applied to the FPD by a steel ball placed in the center of the pontic
      space. One Way Anova, Two Way Anova, Studentized range test (Scheffe's). Results
      showed that the load required for fracturing the unreinforced FPDs varied from
      272 to 998 N. Mean fracture load of reinforced FPDs varied from 536 to 1642 N.
      One-way analysis of variance showed that the position of fibers and the silane
      treatment fibers significantly affected the fracture load. The results of this
      study suggested that the silane treatment of glass fibers had a marked
      improvement in the fracture resistance of FPDs as compared to untreated glass
      fibers. Selective placement of the glass fibers at the undersurface of the pontic
      and the occlusal surface of the interim fixed partial denture showed more
      increase in the fracture resistance as compared to the randomly distributed glass
      fibers. The glass fiber reinforcement is effective in increasing the fracture
      resistance with the effectiveness most evident in interim FPDs with long spans.
      With increase in the length of span of interim fixed partial denture the fracture
      resistance was shown to decrease significantly in all the groups.

PMID- 22379306
TI  - A new simplified beading and boxing procedure for elastic impression.
AB  - Beading and Boxing of impression is taught in most dental colleges. The boxing
      procedure is crucial step to preserve the details of the final impression
      especially of the vestibular area. This article describes an alternative beading
      boxing procedure that is compatible with all impression materials, is efficient,
      simple, inexpensive, and practicable. Use of commercially available instant
      adhesive around the border to act as a joining agent between elastic impressions
      and beading wax or bead made up of base plate wax is advocated in this technique.

PMID- 22379307
TI  - Effect of etchant variability on shear bond strength of all ceramic restorations 
      an in vitro study.
AB  - The present study was carried out to evaluate the effect of pre-luting surface
      treatments by 3 different etchant used at 3 different etching periods and their
      effect on shear bond strength of IPS Empress 2 luted to tooth by dual cure resin
      cement. Fifty samples of ceramic were divided into four groups as group I control
      group: No surface treatment, group II: Etched with Hydrofluoric (HF) acid (4.9%),
      group III: Etched with Ammonium bifluoride acid (9.4%) and group IV: Etched with
      Phosphoric acid (37%). Group II, III and IV were further divided into 3
      Subgroups; namely A, B and C according to the etching periods (20, 60 and 120 s)
      respectively. The shear bond strength was determined by using a Universal testing
      Machine. The morphological changes of the surface treated ceramic samples prior
      to luting to tooth and mode of the fracture failure after shear bond test were
      observed by using a Scanning Electron Microscope. The mean shear bond strength
      was highest when IPS Empress 2 ceramic samples were surface treated using 4.9%
      Hydrofluoric acid gel and 9.4% Ammonium bifluoride acid for 120 s. The least mean
      shear bond strength was noticed in case of control group, where no surface
      treatment was done and samples treated by 37% Phosphoric acid. Thus it could be
      concluded, that Ammonium bifluoride could be an appropriate alternative to be
      used instead of HF acid. 120 s etching showed highest bond strength values for HF
      acid (4.9%) and Ammonium bifluoride (9.4%).

PMID- 22379308
TI  - Evaluation of dimensional stability of autoclavable elastomeric impression
      material.
AB  - Impressions are important sources of cross contamination between patients and
      dental laboratories. As a part of infection control impressions contaminated with
      variety of micro-organisms via blood and oral secretions should be cleaned and
      disinfected or sterilized before being handled in dental laboratory. The purpose
      of this study was to determine the effect of autoclaving on dimensional stability
      of elastomeric impression material (polyvinyl siloxane-Affinis). In this in vitro
      study standardized stainless steel die as per ADA specification number 19 was
      fabricated. Polyvinyl siloxane (Affinis) light body and putty viscosity
      elastomeric impression materials were used. A total of 40 impressions of the
      stainless steel die were made and numeric coding system was used to identify the
      samples. Measurements were made using a measuring microscope. Distance between
      the cross lines CD and C'D' reproduced in the impression were measured before
      autoclaving, immediately after autoclaving and 24 hours after autoclaving and
      dimensional change was calculated. The data obtained was subjected to statistical
      analysis. The mean difference in dimensional change between the three groups was
      not statistically significant (P > 0.05). However the results revealed that there
      was higher mean dimensional change immediately after autoclaving when compared to
      the other 2 time intervals. It is desirable to delay the casting of an
      autoclavable elastomeric impression material by about 24 hours. Though
      disinfection of impression is routinely followed autoclaving of impression is an
      effective method of sterilization.

PMID- 22379309
TI  - The split denture: managing xerostomia in denture patients: a case report.
AB  - Wearing complete dentures can be an extremely uncomfortable experience for the
      people with Xerostomia. Various treatment modalities have been suggested in the
      literature to overcome the problem of xerostomia in complete denture patients.
      Incorporating reservoirs containing salivary substitutes, into dentures, is one
      of these treatment modalities. This paper presents case report of a patient
      suffering from xerostomia who was successfully treated with a new form of
      reservoir dentures. This new split denture technique resulted in a reservoir
      denture that provided good lubrication of the oral tissues, was easily cleaned by
      the wearer and was produced from routine denture materials. Details of its
      design, construction and other potential applications are also presented.

PMID- 22379310
TI  - Pre-surgical management of unilateral cleft lip and palate in a neonate: a
      clinical report.
AB  - Cleft lip and palate deformity is a congenital defect of the middle third of the
      face, consisting of fissures of the upper lip and/or palate. Naso-alveolar
      molding provides excellent results when considered and started early in the
      neonatal. Early treatment is important not only due to esthetic and functional
      concerns, but also for a positive psychological impact it has on the child. In
      the pre-surgical management, an interdisciplinary approach is necessary where an
      Orthodontist and a Prosthodontist play a major role. Also any treatment procedure
      in an infant becomes difficult due to the lack of co-operation from the child.
      This clinical report describes the multidisciplinary approach for complete pre
      surgical management of a neonate with complete unilateral cleft of soft palate,
      hard palate, alveolar ridge and lip.

PMID- 22379311
TI  - Winds of change.

PMID- 22379312
TI  - Will the real author please stand up!
AB  - This is a Guest editorial on the ethics of authorship in scientific publications.
      The editorial analyzes the qualification and roles of an author. It also
      discusses controversial issues and the relevance of the order of authorship in
      bio-medical journal publications.

PMID- 22379313
TI  - To the editors' and authors'.

PMID- 22379314
TI  - Use of 3-d stereolithographic models in oral and maxillofacial surgery.
AB  - OBJECTIVE: To assess the feasibility of the use of 3-dimensional (3-D)
      stereolithographic (SLA) technology in complex maxillofacial reconstructive
      surgery. MATERIALS AND METHODS: 3-D SLA technology was used in the treatment
      planning of complex maxillofacial procedures performed by the Department of Oral
      and Maxillofacial Surgery at Boston University. Specialized 3-D models were
      ordered and utilized for surgical treatment of a variety of indications including
      trauma surgery, temporomandibular joint surgery, orthognathic surgery, secondary
      correction of facial and skull deformities, and extensive jaw pathology. This
      technology was also used in one patient for jaw reconstruction using novel bone
      and tissue engineering techniques. RESULTS: The use of 3-D models in Oral and
      Maxillofacial Surgery significantly improved predictability of clinical outcomes
      when compared to similar treatments without its use. Total operating time was
      reduced which had the benefit of decreasing the duration of general anesthesia
      and reducing wound exposure time. They allowed for assessment of extensive
      traumatic and pathologic defects in three-dimensions prior to surgical
      reconstruction. The models were also useful in the design and fabrication of
      custom prostheses, sizing of bone grafts and allowed for manufacturing of
      scaffolds for bone regeneration. CONCLUSIONS: 3-D SLA models can be very
      effectively used in oral and maxillofacial surgery for multiple indications and
      diverse clinical scenarios. Successful incorporation of this technology for jaw
      bone regeneration using tissue engineering techniques offers exciting new
      prospects for the future.

PMID- 22379315
TI  - Ophthalmic considerations in cleft lip and palate patients.
AB  - Cleft lip and palate (CL and P) represents the second most frequently occurring
      congenital deformity after clubfoot deformity. CL and P could be associated with
      many other structural abnormalities of the adjacent vital structures of the face.
      In this study, an attempt was made to identify the abnormalities of the ocular
      structures seen in patients with isolated CL and P as well as in those with
      syndromic CL and P. Of the 322 patients with cleft lip and palate screened, 27
      (8.3%) had ocular abnormalities. Totally 47 ocular defects were identified in 27
      patients. Abnormalities of the eyelid were the commonest accounting for 22% of
      the total defects (11/47), which includes symblepharon, ectropion, lid colobomas,
      euryblepharon and ptosis. Second commonest abnormality was squint 8/47 (17%)
      followed by orbital defects 8/47 (17%) (Telecanthus and Hypertelorism).
      Abnormalities of the nasolacrimal apparatus 3/47 (6%), refractive errors 7/47
      (15%), dermoids 4/47 (6%), cataract 2/47 (4%) and retinal colobomas 2/47 (4%)
      constituted the rest. Thus, children with cleft lip and palate should be assessed
      as soon as possible after birth by a multidisciplinary team involving the
      Pediatrician, Ophthalmologist and specialists from Maxillofacial, ENT and Plastic
      surgery. The medical problems in this group of children are global and therefore,
      should not be looked at in isolation.

PMID- 22379316
TI  - The correction of post-traumatic pan facial residual deformity.
AB  - Disfiguring post-traumatic deformities of the midface sometimes persist even
      after the treatment. Such deformities, after healing, are among the most
      formidable challenges faced by the surgeons, apart from the psychological impact
      on the patients. Following the basic principles of craniofacial reconstruction
      and with newer techniques, better results can be achieved. Symmetry is key to
      proper reconstruction in general and face in particular. Proper facial projection
      and height must be re-established with harmonious occlusion. Our basic approach
      to the evaluation of deformities and particularly useful techniques for their
      correction are presented, with a representative case of malunited panfacial
      fracture that we treated with an iliac bone onlay grafting for zygoma along with
      correction of mandibular deformity by osteotomies.

PMID- 22379317
TI  - The versatility of temporalis myofascial flap in maxillo-facial reconstruction: a
      clinical study.
AB  - OBJECTIVES: This clinical study was conducted in the department of Oral &
      Maxillofacial Surgery, at our institute, to study the versatility of temporalis
      myofascial flap in maxillofacial reconstruction. METHODS: The study group
      comprised of 20 patients, both male and female patients between the age group of
      6 years and 60 years underwent surgery under general anesthesia and temporalis
      myofascial flap was used for reconstruction of various types of maxillofacial
      defects including maxillectomy defects arising as a result of ablative surgery
      for tumors and treatment of aggressive cysts, as an interposing material in TMJ
      ankylosis surgery and facial reanimation in cases of long standing facial nerve
      paralysis. Following surgery the cases were evaluated for clinical parameters
      weekly for first post-operative month followed by monthly review for a minimum
      period of one and maximum of three years from January 2003 to June 2006. RESULTS:
      Temporalis myofascial flap fared well in 16 out of 20 cases (80%), in remaining
      four cases (20%) three reported back with reankylosis, and in one case of facial
      reanimation flap breakdown occurred due to infection leading to failure of the
      procedure. CONCLUSION: The temporalis myofascial flap is a versatile option for
      reconstruction of moderate to large sized maxillofacial defects, the muscle can
      provide abundant viable and vascular tissue, with minimal to no functional
      morbidity or esthetic deformity at the donor site.

PMID- 22379318
TI  - Mandibular Osteosynthesis: A Comparative Evaluation of Two Different Fixation
      Systems Using 2.0 mm Titanium Miniplates and 3-D Locking Plates.
AB  - PURPOSE: To compare and evaluate postoperative complications and treatment
      outcome in mandibular fracture fixation using 2.0 mm titanium miniplates and 3-D
      locking plates. METHOD: Thirty patients were divided randomly into two groups of
      15 each (including comminuted and malunited fractures). Group A was treated with
      open reduction internal fixation using 2.0 mm miniplates and group B with 3-D
      locking plates. RESULTS: A total of five complications were observed in four
      patients: implant exposure and infection in miniplate group and postoperative
      neurosensory deficit, implant failure and implant exposure in 3-D group.
      CONCLUSION: For fractures in symphysis and parasymphysis region, severely
      displaced angle fractures and for comminuted fractures 3-D locking plate could be
      a better option. In the angle and body region a single miniplate fixed according
      to Champy's technique is easy to place with less surgical time, less surgical
      trauma, is more economical and has similar clinical results.

PMID- 22379319
TI  - Comparison of approaches for the rigid fixation of sub-condylar fractures.
AB  - AIM: The objective of this study was to compare the rate of complications
      encountered on using different incisions to access the fracture site for the open
      reduction and internal fixation of isolated subcondylar fractures. The parameters
      evaluated are: the occurrence of salivary fistula, infection, and injuries to the
      seventh facial nerve. An assessment of the surgical scar was also undertaken.
      MATERIALS AND METHODS: 20 patients who met the previous criteria and were willing
      to participate in the study were placed (five each) into the pre-auricular,
      submandibular, retromandibular transparotid or retromandibular transmassetric
      group based on the incision scar they selected after a description of the
      operation and being explained about the possible complications. RESULTS AND
      CONCLUSION: Comparison of the complications could not ascertain the superiority
      of any approach over the other since the outcomes were not statistically
      significant. However, judging by operator and assistants' subjective assessment,
      the retromandibular approaches seem to provide a more direct visual field and an
      almost straight line access for the fixation of the fracture. The transmassetric
      approach seems to be a safer approach since the nerves encountered can be
      visualized and avoided.

PMID- 22379320
TI  - Platelet concentrates: past, present and future.
AB  - Platelets play a crucial role in hemostasis and wound healing, platelet growth
      factors are well known source of healing cytokines. Numerous techniques of
      autologous platelet concentrates have been developed and applied in oral and
      maxillofacial surgery. This review describes the evolution of the first and
      second generation of platelet concentrates (platelet rich plasma and platelet
      rich fibrin respectively) from their fore runner-fibrin sealants.

PMID- 22379321
TI  - Condylar hyperplasia and facial asymmetry: report of five cases.
AB  - Condylar hyperplasia of mandible is overdevelopment of condyle, unilaterally or
      bilaterally, leading to facial asymmetry, mandibular deviation, malocclusion and
      articular dysfunction. This is a series of five such patients managed at our
      centre.

PMID- 22379322
TI  - Reconstruction of Ala of Nose with Bilobed Flap: A 2 Year Follow-up.
AB  - Basal cell carcinoma accounts for 70-80% of all cutaneous malignancies in the
      head, face and neck region [2]. This article reports a case of basal cell
      carcinoma involving the ala of the nose with the excision of the lesion and
      reconstruction.

PMID- 22379323
TI  - Polymorphous low grade adenocarcinoma: literature review and report of lower lip
      lesion with suspected lung metastasis.
AB  - Polymorphous low grade adenocarcinoma (PLGA) is an uncommon tumour that affects
      minor salivary glands mainly. It was known to be clinically benign and
      histologically polymorphic; sometimes misdiagnosed as pleomorphic adenomas,
      monomorphic adenomas, malignant pleomorphic adenomas, adenoid cystic carcinomas
      and adenocarcinoma not otherwise specified. More information about PLGA is
      cumulating in the current literature with new evidences suggesting that the
      tumour may not be as indolent as it was previously thought. A thorough
      understanding of the clinical and histological behaviour of the lesion has
      serious implications in management. Here, a case of lower lip lesion with
      suspected lung metastasis is reported to exemplify how the clinical behaviour of
      the lesion may affect management.

PMID- 22379324
TI  - Cherubism: case report with review of literature.
AB  - Cherubism is a rare hereditary fibro-osseous lesion characterized by painless
      expansion of jaws in childhood and is known to regress without treatment after
      puberty. Wait and watch approach has been advocated by many authors. The disease
      starts early in life manifesting itself fully in the second decade of life and is
      almost regressed in the third decade. Here, we report two cases of cherubism with
      clinico-radiographic presentation of its classical features in their third and
      fourth decade of life respectively and review the literature.

PMID- 22379325
TI  - Desmoplastic trichilemmoma of the facial region mimicking invasive carcinoma.
AB  - Trichilemmoma is a hamartomatous proliferation arising from cells of hair
      follicle. Its desmoplastic variant simulates an invasive carcinoma. In this
      tumor, the cell of origin seems to be located in the superficial level of the
      hair follicle just below the basement membrane at the sebaceous gland level. We
      present a similar case which presented with an asymptomatic nodular lesion in the
      region above the upper lip on left side. Fine needle aspiration cytology raised
      the cytological possibility of a malignancy for which the lesion was excised. On
      histopathology the lesion was diagnosed as desmoplastic trichilemmoma. The case
      highlights the difficulty encountered in differentiating a benign adnexal tumor
      from malignant lesion based on cytology alone. Moreover, the extensive
      desmoplasia on histopathology raises the suspicion of invasive malignancy which
      requires to be carefully excluded. The superficial features of trichilemmoma and
      lack of cellular atypia is a useful diagnostic clue in such a situation.
      Positivity of CD34 can also be used to differentiate from basal cell carcinomas.
      The case reported here had a solitary lesion, but follow up is required for
      development of more lesions or multiple hamartomas in other organs as a part of
      Cowden's disease.

PMID- 22379326
TI  - Unusual presentation of caustic ingestion and its surgical treatment: a case
      report.
AB  - Treatment and reconstruction of oral scar contracture, is always a challenging
      procedure to restore structure and functions of the oral cavity. We present a
      case of a patient with limited mouth opening who sustained extensive oral scar
      contracture with complete adhesion of tongue to floor of mouth following
      ingestion of caustic soda without his knowledge 4 years back. We performed a
      surgical release of the scar contractures from buccal mucosa on both sides, along
      with a release of the tongue from the floor of the mouth, followed by
      reconstruction of all sites using split skin grafts. Adequate mouth opening and
      tongue movement was achieved. There was a follow up period of 1 month with
      excellent mouth opening and tongue function.

PMID- 22379327
TI  - Wild boar inflicted human injury.
AB  - Interaction between human and animals has increased in recent time regarding the
      fight for habitats. Animal inflicted injuries are mostly associated with the soft
      tissue injury and facial fractures. As literature has documented, this type of
      injuries are most commonly seen in rural communities. This article discusses a
      report a case of soft tissue injury associated with mandibular fracture
      undisplaced cervical spine fracture and review cases reported in the literature.

PMID- 22379328
TI  - Gunshot injury in the neck with an atypical bullet trajectory.
AB  - Gunshot injuries are on a rise in both developed and developing countries, the
      reason for this may be increased access to firearms. Gunshot injuries to the neck
      and maxillofacial region are associated with high morbidity and mortality due to
      the complex anatomy and presence of various vital structures in this region. It
      is indeed a rare finding that a bullet's trajectory passes through the neck
      region and does not damage any vital structures. We present one such case of
      gunshot injury to the neck.

PMID- 22379329
TI  - Maxillofacial Injuries due to Bear Mauling.
AB  - Bear bite injuries have become a common occurrence as the forest covers and
      natural habitats are diminishing. Patients injured in bear attack present with
      different patterns of injuries. A common protocol may not be suitable for the
      management of injuries inflicted by these large wild animals. These animals
      usually attack in remote areas where composite trauma centres do not exist and
      urgent referrals of these patients will have significant effect on the final
      outcome. Limited literature is available describing bear bite management in
      maxillofacial practice. The goal of the present case reports is to document the
      injuries suffered in bear mauling and to add to the literature on the
      conservative management with minimal complications.

PMID- 22379330
TI  - A Bony Landmark 'RAI Triangle' to Prevent 'Misplaced and Misdirected' Medial Cut
      in SSRO.
AB  - 'Rai triangle', a new anatomic landmark on the medial surface of the ramus of the
      mandible which when identified and taken into consideration, may have a definite
      advantage. This is especially in terms of performing the medial horizontal cut
      which is an important and integral part of the sagittal split ramus osteotomy so
      as to avoid a bad split. The objective of this article is to propose an easily
      identifiable bony land mark, which is closely related to lingula of mandible that
      may ease the procedure of osteotomy and avoid bad splits.

PMID- 22379331
TI  - Persistence of Orientia tsutsugamushi in humans.
AB  - We investigated the persistence of viable Orientia tsutsugamushi in patients who
      had recovered from scrub typhus. Blood specimens were available from six patients
      with scrub typhus who were at 1 to 18 months after the onset of the illness. The
      EDTA-treated blood specimens were inoculated into ECV304 cells, and cultures were
      maintained for 7 months. Sequencing of the 56-kDa type-specific antigen gene of
      O. tsutsugamushi was performed to ascertain the homology of isolates. O.
      tsutsugamushi was isolated from all six patients, and nucleotide sequences of
      isolates serially collected from each patient were identical in all five patients
      in whom nucleotide sequences were compared. One patient relapsed 2 days after
      completion of antibiotic therapy; two patients complained of weakness for 1 to
      2.5 months after the illness; one patient underwent coronary angioplasty 6 months
      later; and one patient suffered from a transient ischemic attack 8 months later.
      This finding suggests that O. tsutsugamushi causes chronic latent infection,
      which may be associated with certain clinical illnesses, preceded by scrub
      typhus. Antibiotic therapy abates the symptoms of scrub typhus, but does not
      eradicate O. tsutsugamushi from the human body.

PMID- 22379332
TI  - Prognostic value of left atrium remodeling after primary percutaneous coronary
      intervention in patients with ST elevation acute myocardial infarction.
AB  - The purpose of this study is to assess the relationship between left atrial (LA)
      size and outcome after acute myocardial infarction (AMI) in patients undergoing
      primary percutaneous coronary intervention (PCI) and to evaluate dynamic changes
      in LA size during long-term follow-up. Echocardiographic analyses were performed
      on 253 AMI patients (174 male and 79 female, 65.4 +/- 13.7 yr) undergoing PCI.
      These subjects were studied at baseline and at 12 months. Clinical follow-up were
      done at 30.8 +/- 7.5 months. We assessed LA volume index (LAVI) at AMI-onset and
      at 12-month. Change of LAVI was an independent predictor of new onset of atrial
      fibrillation or hospitalization for heart failure (P = 0.002). Subjects who
      survived the 12-month period displayed an increased LAVI mean of 1.86 +/- 4.01
      mL/m(2) (from 26.1 +/- 8.6 to 28.0 +/- 10.1 mL/m(2), P < 0.001). The subject
      group that displayed an increased LAVI correlated with a low left ventricular
      ejection fraction, large left ventricle systolic and diastolic dimensions and an
      enlarged LA size. In conclusion, change of LAVI is useful parameter to predict
      subsequent adverse cardiac event in AMI patients. Post-AMI echocardiographic
      evaluation of LAVI provides important prognostic information that is
      significantly greater than that obtained from clinical and laboratory parameters
      alone.

PMID- 22379333
TI  - Obesity phenotype and coronary heart disease risk as estimated by the Framingham
      risk score.
AB  - There are conflicting data as to whether general or abdominal obesity is a better
      predictor of cardiovascular risk. This cross-sectional study involved 4,573
      subjects aged 30 to 74 yr who participated in the Fourth Korea National Health
      and Nutrition Examination Survey conducted in 2008. Obesity phenotype was
      classified by means of body mass index (BMI) and waist circumference (WC), and
      participants were categorized into 4 groups. Individuals' 10-yr risk of coronary
      heart diseases (CHD) was determined from the Framingham risk score. Subjects with
      obese WC had a higher proportion of high risk for CHD compared to the normal WC
      group, irrespective of BMI level. Relative to subjects with normal BMI/normal WC,
      the adjusted odds ratios (ORs) of normal BMI/obese WC group (OR 2.93 [1.70, 5.04]
      and OR 3.10 [1.49, 6.46]) for CHD risk in male were higher than obese BMI/obese
      WC group (OR 1.91 [1.40, 2.61] and OR 1.70 [1.16, 2.47]), whereas the adjusted
      ORs of obese BMI/obese WC group (OR 1.94 [1.24, 3.04] and OR 3.92 [1.75, 8.78])
      were higher than the others in female. Subjects with obese BMI/normal WC were not
      significantly associated with 10-yr CHD risk in men (P = 0.449 and P = 0.067) and
      women (P = 0.702 and P = 0.658). WC is associated with increased CHD risk
      regardless of the level of BMI. Men with normal BMI and obese WC tend to be
      associated with CHD risk than those with obese BMI and obese WC.

PMID- 22379334
TI  - Different response of body weight change according to ketonuria after fasting in
      the healthy obese.
AB  - The relationship between obesity and ketonuria is not well-established. We
      conducted a retrospective observational study to evaluate whether their body
      weight reduction response differed by the presence of ketonuria after fasting in
      the healthy obese. We used the data of 42 subjects, who had medical records of
      initial urinalysis at routine health check-up and follow-up urinalysis in the out
      patient clinic, one week later. All subjects in the initial urinalysis showed no
      ketonuria. However, according to the follow-up urinalysis after three subsequent
      meals fasts, the patients were divided into a non-ketonuria group and ketonuria
      group. We compared the data of conventional low-calorie diet programs for 3
      months for both groups. Significantly greater reduction of body weight (-8.6 +/-
      3.6 kg vs -1.1 +/- 2.2 kg, P < 0.001), body mass index (-3.16 +/- 1.25 kg/m(2) vs
      -0.43 +/- 0.86 kg/m(2), P < 0.001) and waist circumference (-6.92 +/- 1.22 vs 
      2.32 +/- 1.01, P < 0.001) was observed in the ketonuria group compared to the non
      ketonuria group. Fat mass and lean body mass were also more reduced in the
      ketonuria group. In addition, serum free fatty acid concentration after
      intervention in the ketonuria group showed significant more increment than in the
      non-ketonuria group. The presence of ketonuria after fasting may be a predicting
      factor of further body weight reduction.

PMID- 22379335
TI  - Health-related quality of life using the EuroQol 5D questionnaire in Korean
      patients with type 2 diabetes.
AB  - We aimed; 1) to determine the validity of the EuroQol 5D (EQ-5D) for the health
      related quality of life (HRQOL) of Korean patients with type 2 diabetes, and 2)
      to identify associated factors of the HRQOL of these patients. Follow-up surveys
      were conducted for consecutive patients with type 2 diabetes. HRQOL was assessed
      using the EQ-5D and the Short Form-36 (SF-36). The validity of EQ-5D was assessed
      with the perspectives of known group, convergent and discriminant validity.
      Additionally, a linear mixed model using a backward elimination was used for
      identify associated factors. Of the 1,072 patients included in the first survey,
      858 (80.0%) completed the questionnaires in the follow-up. In the known group
      validity, the problem rates in each EQ-5D dimension were highest among women,
      elderly people, and less-educated subjects. The Spearman's rho between the EQ-5D
      and the SF-36 scales were larger in the comparable dimensions than those in the
      less comparable dimensions. In the final model, we found that sex, age,
      education, body mass index, atrial fibrillation, stroke, and retinopathy were
      statistically significant. Our data suggest that the EQ-5D is a valid tool for
      Korean patients with type 2 diabetes and that various factors could affect their
      HRQOL.

PMID- 22379336
TI  - Postoperative nutritional effects of early enteral feeding compared with total
      parental nutrition in pancreaticoduodectomy patients: a prosepective, randomized
      study.
AB  - The benefits of early enteral feeding (EEN) have been demonstrated in
      gastrointestinal surgery. But, the impact of EEN has not been elucidated yet. We
      assessed the postoperative nutritional status of patients who had undergone
      pancreaticoduodenectomy (PD) according to the postoperative nutritional method
      and compared the clinical outcomes of two methods. A prospective randomized trial
      was undertaken following PD. Patients were randomly divided into two groups; the
      EEN group received the postoperative enteral feed and the control group received
      the postoperative total parenteral nutrition (TPN) management. Thirty-eight
      patients were included in our analyses. The first day of bowel movement and time
      to take a normal soft diet was significantly shorter in EEN group than in TPN
      group. Prealbumin and transferrin were significantly reduced on post-operative
      day (POD) 7 and were slowly recovered until POD 90 in the TPN group than in the
      EEN group. EEN group rapidly recovered weight after POD 21 whereas it was
      gradually decreased in TPN group until POD 90. EEN after PD is associated with
      preservation of weight compared with TPN and impact on recovery of digestive
      function after PD.

PMID- 22379337
TI  - Spontaneously reported hepatic adverse drug events in Korea: multicenter study.
AB  - Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each
      country, reflecting different patterns of prescription, socioeconomic status, and
      culture. The purpose of this study was to assess the suspected cause of hepatic
      ADRs using the spontaneously reported pharmacovigilance data from Korea. A total
      of 9,360 spontaneously reported adverse drug events (ADEs) from nine
      Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by
      calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs
      were reported. The most frequently prescribed drug classes inducing hepatic ADEs
      were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones,
      non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins.
      ROR values were especially high in anti-tuberculosis drugs, systemic antifungal
      drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines.
      Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs
      1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs
      0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%)
      were significantly more common in hepatic ADE group. In conclusion, anti
      infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects
      of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such
      reactions is needed for the prescription of these drugs.

PMID- 22379338
TI  - Genetic analysis of dystrophin gene for affected male and female carriers with
      Duchenne/Becker muscular dystrophy in Korea.
AB  - Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessive disorders
      caused by mutation in dystrophin gene. We analyzed the results of a genetic test
      in 29 DMD/BMD patients, their six female relatives, and two myopathic female
      patients in Korea. As the methods developed, we applied different procedures for
      dystrophin gene analysis; initially, multiplex polymerase chain reaction was
      used, followed by multiplex ligation-dependent probe amplification (MLPA).
      Additionally, we used direct DNA sequencing for some patients who had negative
      results using the above methods. The overall mutation detection rate was 72.4%
      (21/29) in DMD/BMD patients, identifying deletions in 58.6% (17/29). Most of the
      deletions were confined to the central hot spot region between exons 44 and 55
      (52.9%, 7/19). The percentage of deletions and duplications revealed by MLPA was
      45.5% (5/11) and 27.2% (3/11), respectively. Using the MLPA method, we detected
      mutations confirming their carrier status in all female relatives and symptomatic
      female patients. In one patient in whom MLPA revealed a single exon deletion of
      the dystrophin gene, subsequent DNA sequencing analysis identified a novel
      nonsense mutation (c.4558G > T; Gln1520X). The MLPA assay is a useful
      quantitative method for detecting mutation in asymptomatic or symptomatic
      carriers as well as DMD/BMD patients.

PMID- 22379339
TI  - Surgical treatment for intra-thoracic migration of acupuncture needles.
AB  - The aim of this study was to introduce the experience of diagnosis and treatment
      for patients with migrated acupuncture needle to pleural cavity and or lung
      parenchyma. We had treated 5 patients who had acupuncture needles in their
      thoracic cavity from January 2000 to September 2009. The mean age was 55.8 yr
      old. All patients suffered from the sequelae of the cerebrovascular accident and
      had been treated with acupuncture. They had drowsiness and hemiplegic or
      quadriplegic motor activity. Fever and dyspnea were main symptoms when referred
      to us. Diagnosis was made by the chest radiography and chest computed tomography
      which revealed straight metallic materials in their thoracic cavity. The needles
      were removed via thoracotomy or thoracoscopic procedures. Pleural decortications
      were also needed in four patients. Thoracoscopic surgery was successfully
      performed in two patients. After the removal all patients became symptomless.
      Although we experienced only five patients who have migrated acupuncture needles
      in thoracic cavity, we suggest that thoracoscopic removal of the needle with or
      without pleural decortication is the most optimal modality of treatment in those
      patients.

PMID- 22379340
TI  - Prevalence of treated epilepsy in Korea based on national health insurance data.
AB  - The Korean national health security system covers the entire population and all
      medical facilities. We aimed to estimate epilepsy prevalence, anticonvulsant
      utilization pattern and the cost. We identified prevalent epilepsy patients by
      the prescription of anticonvulsants under the diagnostic codes suggesting seizure
      or epilepsy from 2007 Korean National Health Insurance databases. The information
      of demography, residential area, the kind of medical security service reflecting
      economic status, anticonvulsants, and the costs was extracted. The overall
      prevalence of treated epilepsy patients was 2.41/1,000, and higher for men than
      women. The age-specific prevalence was the lowest in those in their thirties and
      forties. Epilepsy was more prevalent among lower-income individuals receiving
      medical aid. The regional prevalence was the highest in Jeju Island and lowest in
      Ulsan city. New anticonvulsants were more frequently used than old
      anticonvulsants in the younger age group. The total annual cost of epilepsy or
      seizure reached 0.46% of total medical expenditure and 0.27% of total expenditure
      on health. This is the first nationwide epidemiological report issued on epilepsy
      in Korea. Epilepsy prevalence in Korea is comparable to those in developed
      countries. Economic status and geography affect the prevalence of epilepsy.

PMID- 22379341
TI  - Increased expression of EMMPRIN and VEGF in the rat brain after gamma
      irradiation.
AB  - The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to
      play a key regulatory role in pathological angiogenesis. A elevated activation of
      vascular endothelial growth factor (VEGF) following radiation injury has been
      shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of
      EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery
      (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes
      in a rat model of radiation injury following GKS and examined potential
      associations between EMMPRIN and VEGF expression. Adult male rats were subjected
      to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and
      VEGF expression were markedly upregulated in the target area at 8-12 weeks after
      GKS compared with the control group by western blot, immunohistochemistry, and RT
      PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals
      colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated
      that increased EMMPRIN expression was correlated with increased VEGF levels in a
      temporal manner. This is the first study to show that EMMPRIN and VEGF may play a
      role in radiation injuries of the central nervous system after GKS.

PMID- 22379343
TI  - Characteristics of patients who visit the emergency department with self
      inflicted injury.
AB  - During visits to emergency medical facilities, the primary care of and risk
      identification for individuals who have attempted suicide is considered an
      important element in suicide prevention. With the ultimate goal of helping to
      prevent suicide, the aim of the present study was to determine the
      characteristics of patients with self-inflicted injuries who presented in the
      emergency department. Patients with self-inflicted injuries who visited 1 of 3
      sentinel emergency medical centers from 2007 through 2009 were included in the
      study. The characteristics, methods, and reasons for suicide attempts were
      evaluated. Moreover, predictors of severe outcomes were evaluated. A total of
      2,996 patients with self-inflicted injuries visited the three centers during a
      period of 3 yr. The male-to-female suicide ratio was 1:1.38 (P < 0.001). The mean
      age was 41 yr. Poisoning was the most common method of self-inflicted injury
      (68.7%) among all age groups. Medication was the primary means of injury in the <
      50 age group, and the use of agricultural chemicals was the primary means in the
      >= 50 age group. The reasons for attempting suicide varied among the age groups.
      The predictors of severe outcome are male gender, older age, and not having
      consumed alcohol.

PMID- 22379342
TI  - Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.
AB  - Glycosaminoglycans are important structural components in the skin and exist as
      various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of
      the glycosaminoglycans, is composed of repeated disaccharide units, which are
      glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To
      investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans
      (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin
      were examined by immunohistochemistry and real-time quantitative polymerase chain
      reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n =
      4-7). HS staining revealed that 2 MED of UV irradiation increased its expression,
      and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that
      UV irradiation increased their protein levels. However, analysis by real-time
      qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and
      decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA
      level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA
      levels were increased, but exostosin-2 was decreased by UV irradiation. UV
      induced matrix metalloproteinase-1 expression was confirmed for proper
      experimental conditions. Acute UV irradiation increases HS and HSPG levels in
      human skin, but their increase may not be mediated through their transcriptional
      regulation.

PMID- 22379344
TI  - Post-influenza pneumonia caused by the USA300 community-associated methicillin
      resistant Staphylococcus aureus in Korea.
AB  - Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most
      successful community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA
      has been predominant in Korea, and there has been no report of infections by the
      USA300 strain except only one case report of perianal infection. Here, we
      describe the first case of pneumonia caused by the USA300 strain following
      pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever
      and cough and chest radiograph showed pneumonic consolidation at the right lower
      lung zone. He received a ventilator support because of respiratory failure. PCR
      for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture
      of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed
      that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE
      patterns showed that this isolate was the same pulsotype as the USA300 strain.

PMID- 22379345
TI  - Aspergillus-associated cerebral aneurysm successfully treated by endovascular and
      surgical intervention with voriconazole in lupus nephritis patient.
AB  - During the last five decades, long-term therapy with immunosuppressive agents
      such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has
      enhanced both patient survival and renal survival in patients with diffuse
      proliferative lupus nephritis. Nevertheless, severe side effects such as
      infectious complications remain the main cause of morbidity and mortality.
      Central nervous system aspergillosis is uncommon but life-threatening in lupus
      patients. In this single-patient case study, carotid aneurysm with sphenoidal
      sinusitis was suspected when severe epistaxis occurred during cyclophosphamide
      pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed
      to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae,
      indicating aspergillosis. Three months after stopping voriconazole treatment, two
      cerebral aneurysms that were revealed on MR images were successfully removed by
      aneurysmal clipping. The patient remained alive at one-year follow-up with lupus
      nephritis in remission. The rarity and high mortality of aspergillus-related
      fungal aneurysms have led to most cases being recognized postmortem. However,
      such aneurysms must be diagnosed early to prevent fatal complications by
      performing appropriate management such as surgical procedure or endovascular
      intervention.

PMID- 22379346
TI  - Jejunal variceal bleeding successfully treated with percutaneous coil
      embolization.
AB  - A 52-yr-old male with alcoholic liver cirrhosis was hospitalized for
      hematochezia. He had undergone small-bowel resection due to trauma 15 yr
      previously. Esophagogastroduodenoscopy showed grade 1 esophageal varices without
      bleeding. No bleeding lesion was seen on colonoscopy, but capsule endoscopy
      showed suspicious bleeding from angiodysplasia in the small bowel. After 2 weeks
      of conservative treatment, the hematochezia stopped. However, 1 week later, the
      patient was re-admitted with hematochezia and a hemoglobin level of 5.5 g/dL.
      Capsule endoscopy was performed again and showed active bleeding in the mid
      jejunum. Abdominal computed tomography revealed a varix in the jejunal branch of
      the superior mesenteric vein. A direct portogram performed via the transhepatic
      route showed portosystemic collaterals at the distal jejunum. The patient
      underwent coil embolization of the superior mesenteric vein just above the
      portosystemic collaterals and was subsequently discharged without re-bleeding. At
      8 months after discharge, his condition has remained stable, without further
      bleeding episodes.

PMID- 22379347
TI  - Tuberculous pericarditis presenting as multiple free floating masses in
      pericardial effusion.
AB  - Pericarditis is a rare manifestation of tuberculosis (Tb) in children. A 14-yr
      old Korean boy presented with cardiac tamponade during treatment of pulmonary
      tuberculosis. He developed worsening anemia and persistent fever in spite of anti
      tuberculosis medications. Echocardiography found free floating multiple discoid
      masses in the pericardial effusion. The masses and exudates were removed by
      pericardiostomy. The masses were composed of pink, amorphous meshwork of threads
      admixed with degenerated red blood cells and leukocytes with numerous acid-fast
      bacilli, which were confirmed as Mycobacterium species by polymerase chain
      reaction. The persistent fever and anemia were controlled after pericardiostomy.
      This is the report of a unique manifestation of Tb pericarditis as free floating
      masses in the effusion with impending tamponade.

PMID- 22379348
TI  - Unexpected fatal hypernatremia after successful cardiopulmonary resuscitation
      with therapeutic hypothermia: a case report.
AB  - Central diabetes insipidus (DI), characterized by unexpected fatal hypernatremia,
      is a rare complication after successful cardiopulmonary resuscitation with
      therapeutic hypothermia, but may be potentially fatal if recognition is delayed.
      We describe here a patient who experienced cardiac arrest due to a pulmonary
      embolism, followed by successful resuscitation after induction of therapeutic
      hypothermia. The patient, however, suddenly developed unexpected hypernatremia
      with increased urine output and was diagnosed with central DI as a complication
      of cerebral edema, and eventually died. Our findings suggest that central DI
      should be considered as a possible complication following unexpected
      hypernatremia with increased urine output during therapeutic hypothermia and that
      desmopressin acetate should be used to treat central DI.

PMID- 22379350
TI  - Presence of evolutionary pressures or genotyping error.

PMID- 22379349
TI  - Positive rates of 2009 novel influenza A (H1N1) was high in school-aged
      individuals: significance in pandemic control.
AB  - In this study, data from a pandemic H1N1 outbreak in Korea were analyzed
      according to time, geography (districts), and age. A total of 252,271 samples
      collected nationwide were referred to the Greencross Reference Laboratory from
      June 2009 to February 2010 for H1N1 confirmation testing. Of these samples,
      105,300 (41.7%) were H1N1-positive. With time, positivity was highest (57.0%)
      from October 26 - November 1 (4 weeks after Chuseok). The positive rates among
      districts show the highest value in Ulsan City (63.1%) and the lowest in
      Gyeongnam Province (32.8%). The positive rates for ages 0-2, 3-5, 6-11, 12-17, 18
      20, 21-30, 31-40, 41-50, 51-60, and > 60 yr were 17.0%, 33.1%, 56.2%, 55.5%,
      55.3%, 41.5%, 28.2%, 30.5%, 31.1%, and 16.8%, respectively, indirectly indicating
      propagation of H1N1 through schools. Pandemic control should involve school
      targeted strategies.

PMID- 22379352
TI  - Children in poverty: Can public policy alleviate the consequences?

PMID- 22379353
TI  - Role models for pregnancy, birth, and breastfeeding.
AB  - In this column, the editor of The Journal of Perinatal Education discusses how
      the media provide role models-good and bad-for pregnancy, birth, and
      breastfeeding. There is a critical need for more positive role models that
      promote natural, safe, and healthy pregnancy and birth. The editor also describes
      the contents of this issue, which offer a broad range of resources, research, and
      inspiration for childbirth educators in their efforts to promote natural, safe,
      and healthy birth.

PMID- 22379354
TI  - Dayton William Dix's Birth Story.
AB  - In this birth story, a young mother relates her experience of moving beyond fear
      of labor and birth and developing confidence in her ability to give birth without
      an epidural. Knowledge and support, including the support of a doula, during the
      last months of pregnancy helped this mother change her plans for the labor and
      birth. This story highlights the importance of continuous emotional and physical
      support and how knowledge and confidence set the stage for a satisfying, safe,
      and healthy birth.

PMID- 22379355
TI  - Teaching and learning birth: "help all to know".
AB  - This guest editorial explores the idea that our worldview, regardless of
      education, influences our childbirth practices, sometimes interfering with
      achieving the goals of our discipline. Over time, we have lost our ability to
      support women through the process of childbirth so that they emerge as strong,
      healthy women. The high road ahead is to teach everyone, including ourselves,
      that we need to provide optimal, evidence-based care. Pursuing this path will
      take courage and commitment.

PMID- 22379356
TI  - Construct validity of the childbirth trauma index for adolescents.
AB  - The potentially traumatic nature of childbirth for adult mothers has been
      confirmed in research; however, adolescent childbirth trauma is unexplored. This
      article presents research on the construct validity of the Childbirth Trauma
      Index by providing a conceptual analysis of psychological childbirth trauma,
      factor validity of the Childbirth Trauma Index, and discussion of testing the
      Childbirth Trauma Index via contrasted-groups approach. Childbirth trauma can
      result in an acute stress reaction or actual posttraumatic stress disorder. Using
      subjective reports, the Impact of Event Scale, and the Childbirth Trauma Index,
      an appraisal of birth trauma, trauma impact, and indicators associated with
      childbirth trauma were revealed among 112 adolescents. Clinical implications and
      research recommendations are offered.

PMID- 22379357
TI  - Being a resource for both mother and child: fathers' experiences following a
      complicated birth.
AB  - The aim of this study was to describe fathers' experiences of being present on a
      postnatal ward and during the first days at home following a complicated birth.
      Fifteen fathers were interviewed, and content analysis was used for the analysis.
      The theme illustrated that fathers were a resource for both mother and child
      through practical and emotional engagement. The categories describe how the
      father empowers the mother and illustrates adapting to new family roles.
      Following complicated birth, fathers should be invited to stay around-the-clock
      on postnatal wards because it gives them the opportunity to place their resources
      at the disposal of mother and child. In antenatal courses, fathers should be
      prepared for their empowering role after a complicated birth.

PMID- 22379358
TI  - Comparisons in perceived importance of and needs for maternal gestational weight
      information between african american and caucasian pregnant women.
AB  - This study compared the perceived importance of and needs for maternal
      gestational weight information between African American and Caucasian pregnant
      women. A secondary analysis of data from 113 pregnant women (82 African Americans
      and 31 Caucasians) attending an inner-city prenatal clinic was conducted for this
      study. Perceived importance of and needs for information were measured in five
      areas: (1) nutrition, (2) prenatal vitamins, (3) rest/activity balance, (4)
      exercise, and (5) appropriate weight gain. African American women demonstrated
      significantly higher perceived importance of and needs for information on
      rest/activity balance and appropriate weight gain than Caucasian women. Exercise
      information was rated lower in importance but was most needed by both African
      American and Caucasian women. Education programs about maternal gestational
      weight need to be cognizant of ethnic women's needs.

PMID- 22379359
TI  - Grand Multiparous Women's Perceptions of Birthing, Nursing Care, and Childbirth
      Technology.
AB  - This qualitative descriptive study explored grand multiparous women's perceptions
      of the evolving changes in birthing, nursing care, and technology. A purposive
      sample of grand multiparous women (N = 13) from rural, eastern Washington State
      were interviewed as they shared their 105 birth stories. Eight themes were
      identified: (1) providing welcome care, (2) offering choices, (3) following birth
      plans, (4) establishing trust and rapport, (5) being an advocate, (6) providing
      reassurance and support, (7) relying on electronic fetal monitors and assessments
      versus nursing presence, and (8) having epidurals coupled with loss of bodily
      cues. Results from this study may be used to educate women, intrapartum nurses,
      and childbirth educators on nursing care and on the evolving use of technology to
      better manage intrapartum care in hospitals. The results can also add to the
      extant knowledge of childbirth nursing practices.

PMID- 22379360
TI  - Lamaze breathing: what every pregnant woman needs to know.
AB  - Lamaze breathing historically is considered the hallmark of Lamaze preparation
      for childbirth. This column discusses breathing in the larger context of
      contemporary Lamaze. Controlled breathing enhances relaxation and decreases
      perception of pain. It is one of many comfort strategies taught in Lamaze
      classes. In restricted birthing environments, breathing may be the only
      nonpharmacological comfort strategy available to women. Conscious breathing and
      relaxation, especially in combination with a wide variety of comfort strategies,
      can help women avoid unnecessary medical intervention and have a safe, healthy
      birth.

PMID- 22379361
TI  - PREPARATIVE ISOLATION AND PURIFICATION OF FOUR FLAVONOIDS FROM DAPHNE GENKWA
      SIEB. ET ZUCC. BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY.
AB  - Four flavonoids including luteolin, apigenin, 3'-hydroxygenkwanin and genkwanin
      were isolated and purified from Daphne genkwa Sieb. et Zucc. by high-speed
      countercurrent chromatography (HSCCC). Preparative HSCCC with a two-phase solvent
      system composed of n-hexane-ethyl acetate-methanol-water (5:7:5:5, v/v) was
      successfully performed by increasing the flow rate of the mobile phase from 1.2
      to 2.0 mL/min after 260 min. In a one-step operation, 150 mg of the extracts of
      D. genkwa was separated to yield 8 mg of luteolin, 25.8 mg of apigenin, 23.6 mg
      of 3'-hydroxygenkwanin and 35.3 mg genkwanin with the purities of 91.2, 97.4,
      94.3 and 95.8%, respectively, analyzed by HPLC using area normalization method.
      The chemical structures of the four compounds were identified by HPLC, ESI-MS,
      and (1)H NMR.

PMID- 22379364
TI  - The effects of acupressure on severity of primary dysmenorrhea.
AB  - BACKGROUND: Dysmenorrhea constitutes one of the most frequent disorders in women
      of a fertile age. The objective of this research was to determine the effects of
      acupressure at Sanyinjiao (SP6) point and DiJi (SP8) point on pain severity of
      primary dysmenorrhea and the associated systemic symptoms. MATERIALS AND METHODS:
      In this crossover clinical trial, 50 females aged 18-30 years old who met the
      study criteria and were under the care of Sarpolezahab Health Center were
      selected. Subjects were randomly assigned to one of two groups and evaluated
      during three menstrual cycles. We evaluated pain severity using the McGill pain
      scale and associated systemic symptoms using a verbal multidimensional scoring
      system. Data acquired from 42 cases were analyzed using SPSS software, with a P
      value of <0.05 considered significant. RESULTS: The findings of our study
      indicate that the severity of dysmenorrhea pain diminishes significantly for up
      to 2 hours following treatment with acupressure at the SP6 and SP8 points (P <
      0.001). Furthermore, the severity of associated systemic symptoms reduced
      significantly after acupressure at the SP6 and SP8 points, except for nausea and
      vomiting. Comparison of the severity of systemic symptoms with acupressure at the
      SP6 and SP8 points revealed no significant difference except for severity of
      fatigue, which was reduced significantly further with SP6 point compared to SP8
      point (P = 0.004). CONCLUSION: Acupressure at the SP6 and SP8 points can reduce
      pain severity of dysmenorrhea for up to 2 hours after application, and these
      points may be used to alleviate the severity of systemic symptoms accompanying
      dysmenorrhea.

PMID- 22379363
TI  - The effect of reminder systems on patients' adherence to treatment.
AB  - BACKGROUND: Patient adherence is an important component of the treatment of
      chronic disease. An understanding of patient adherence and its modulating factors
      is necessary to correctly interpret treatment efficacy and barriers to
      therapeutic success. PURPOSE: This meta-analysis aims to systematically review
      published randomized controlled trials of reminder interventions to assist
      patient adherence to prescribed medications. METHODS: A Medline search was
      performed for randomized controlled trials published between 1968 and June 2011,
      which studied the effect of reminder-based interventions on adherence to self
      administered daily medications. RESULTS: Eleven published randomized controlled
      trials were found between 1999 and 2009 which measured adherence to a daily
      medication in a group receiving reminder interventions compared to controls
      receiving no reminders. Medication adherence was measured as the number of doses
      taken compared to the number prescribed within a set period of time. Meta-
      analysis showed a statistically significant increase in adherence in groups
      receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95%
      CI for mean: 0.8% to 22.4%). Self-reported and electronically monitored adherence
      rates did not significantly differ (68.04% versus 63.67%, P = 1.0). Eight of
      eleven studies showed a statistically significant increase in adherence for at
      least one of the reminder group arms compared to the control groups receiving no
      reminder intervention. LIMITATIONS: The data are limited by imperfect measures of
      adherence due to variability in data collection methods. It is also likely that
      concomitant educational efforts in the study populations, such as instructions
      regarding proper administration and importance of correct dosing schedules,
      contributed to improved patient adherence, both in reminder and control arms. The
      search strategy could have missed relevant studies which were categorized by
      disease rather than adherence. CONCLUSIONS: Reminder-based interventions may
      improve adherence to daily medications. However, the interventions used in these
      studies, which included reminder phone calls, text messages, pagers, interactive
      voice response systems, videotelephone calls, and programmed electronic
      audiovisual reminder devices, are impractical for widespread implementation, and
      their efficacy may be optimized when combined with alternative adherence
      modifying strategies. More practical reminder-based interventions should be
      assessed to determine their value in improving patient adherence and treatment
      outcomes.

PMID- 22379365
TI  - Improving patient-physician dialog: commentary on the results of the MS Choices
      survey.
AB  - Achieving good long- and short-term adherence to treatment for chronic diseases
      is important if patients are to gain the full benefits of treatment. Several
      barriers to adherence in multiple sclerosis (MS) have been identified and the
      healthcare team should work with patients to help them to overcome these
      obstacles. The MS Choices survey explored patient and physician perspectives on
      key aspects of MS diagnosis, treatment adherence, and disease management with the
      aim of improving understanding of the factors that influence patient behavior
      regarding treatment adherence. The survey found some important differences
      between patient and physician responses and here these findings are discussed in
      the context of personal clinical experience. Further, the possible implications
      of these findings for routine practice have been considered, and strategies that
      should be employed by MS physicians and nurses to help patients to adhere to
      their prescribed treatment are suggested.

PMID- 22379367
TI  - Supply side economics - the Canadian way.

PMID- 22379368
TI  - The new Genetico-Racial Skin Classification: How to maximize the safety of any
      peel or laser treatment on any Asian, Caucasian or Black patient.
AB  - The popular skin classifications, notably the 'Fitzpatrick' and 'Obaji'
      classifications, are primarily based on skin colour. Other criteria are
      occasionally considered, such as the degree of skin oiliness, thickness,
      sensibility, etc. Although these classifications are easy to understand and
      apply, their simplicity limits their precision, sophistication and
      applicability.The new genetico-racial skin classification proposed herein
      suggests that skin response to any peel or laser treatment is genetically
      programmed and is, therefore, linked to the genetic and racial origin of the
      patient. In other words, in addition to skin colour, the patient's facial
      features and ancestry should be taken into account when classifying any skin.The
      new genetico-racial skin classification enables the physician to determine with
      great precision, and before any peel or laser treatment, the level of the
      patient's suitability and the expected postoperative outcomes; therefore,
      reducing the likelihood of complications.

PMID- 22379366
TI  - Correcting magnesium deficiencies may prolong life.
AB  - The International Space Station provides an extraordinary facility to study the
      accelerated aging process in microgravity, which could be triggered by
      significant reductions in magnesium (Mg) ion levels with, in turn, elevations of
      catecholamines and vicious cycles between the two. With space flight there are
      significant reductions of serum Mg (P < 0.0001) that have been shown in large
      studies of astronauts and cosmonauts. The loss of the functional capacity of the
      cardiovascular system with space flight is over ten times faster than the course
      of aging on Earth. Mg is an antioxidant and calcium blocker and in space there is
      oxidative stress, insulin resistance, and inflammatory conditions with evidence
      in experimental animals of significant endothelial injuries and damage to
      mitochondria. The aging process is associated with progressive shortening of
      telomeres, repetitive DNA sequences, and proteins that cap and protect the ends
      of chromosomes. Telomerase can elongate pre-existing telomeres to maintain length
      and chromosome stability. Low telomerase triggers increased catecholamines while
      the sensitivity of telomere synthesis to Mg ions is primarily seen for the longer
      elongation products. Mg stabilizes DNA and promotes DNA replication and
      transcription, whereas low Mg might accelerate cellular senescence by reducing
      DNA stability, protein synthesis, and function of mitochondria. Telomerase, in
      binding to short DNAs, is Mg dependent. On Earth, in humans, a year might be
      required to detect changes in telomeres, but in space there is a predictably much
      shorter duration required for detection, which is therefore more reasonable in
      time and cost. Before and after a space mission, telomere lengths and telomerase
      enzyme activity can be determined and compared with age-matched control rats on
      Earth. The effect of Mg supplementation, both on maintaining telomere length and
      extending the life span, can be evaluated. Similar studies in astronauts would be
      fruitful.

PMID- 22379369
TI  - Liposuction infiltration: The Quito formula - a new approach based on an old
      concept.
AB  - INTRODUCTION: Liposuction is a highly sought after surgical procedure. Despite
      its popularity, not all of the factors associated with its execution are well
      understood. No well-established guidelines exist for plastic surgeons regarding
      the subcutaneous infiltration of fluid and, thus, the procedure is often
      performed subjectively. OBJECTIVE: To establish the usefulness of the Quito
      formula (infiltrate volume = weight [kg] * percentage of body surface to be
      liposuctioned * 2.4 [mL]) for calculating the volume of fluid to be infiltrated
      subcutaneously during small-volume liposuction performed under epidural
      anesthesia. METHODS: A prospective study was conducted on a group of 50 patients
      who were candidates for liposuction on multiple body parts between November 2004
      and February 2010. RESULTS: The maximum volume of infiltrate was 5000 mL and the
      maximum volume of aspirate was 4500 mL, with a 30% total aspirated area. No
      patient required blood transfusion, and there were no major complications.
      However, one patient presented with a small local infection, another with a
      sacral seroma and two patients had postdural puncture headaches. No patient
      showed clinical signs consistent with overhydration, dehydration, pulmonary
      embolism, fat embolism or lidocaine intoxication. CONCLUSIONS: When performing
      small-volume liposuction, subcutaneous infiltration using the Quito formula to
      calculate the volume of infiltrate proved to be useful, safe and objective.

PMID- 22379370
TI  - Obtaining high cure rates for challenging facial malignancies: A new method for
      producing rapid, accurate, high-quality frozen sections.
AB  - PURPOSE: The authors developed a new system to provide rapid, accurate, full-face
      frozen sections. OBJECTIVE: To evaluate the efficacy of the system when applied
      to the treatment of nonmelanoma cutaneous malignancies using Mohs micrographic
      surgery (MMS). METHODS: Patients undergoing MMS procedures between 2003 and 2007
      for nonmelanoma head and neck cutaneous malignancies were prospectively
      collected. Specimens were prepared either in a traditional cryostat-based manner
      or using the new system. RESULTS: A total of 196 patients with 234 head and neck
      nonmelanoma cutaneous malignancies were included. The majority of tumours were
      basal cell carcinomas (89.5%). Of these, 38% demonstrated aggressive histologies
      (sclerosing or micronodular), and 30% were recurrent. On average, two levels
      (range one to six) and four blocks (range two to 23) were required to obtain
      clear margins. The mean defect size was 3.68 cm(2) (range 0.13 cm(2) to 37.68
      cm(2)). Over the five-year study period, there were two recurrences in 234 cases
      (less than 1%), which compares favourably with other MMS series. The new system
      was associated with a shorter operative time than traditional specimen
      preparation (102 min versus 131 min; P=0.004). The new and traditional specimen
      preparation groups were similar in terms of the number of previous recurrences
      (29% versus 30%; P=1.00), defect size (3.7 cm(2) versus 4.0 cm(2); P=0.81) and
      the number of levels required (1.9 versus 1.5; P=0.05). CONCLUSIONS: The new
      system enables fast, accurate, full-face frozen section specimens that are ideal
      for MMS. The speed of specimen preparation is demonstrated by faster operative
      times, and a low recurrence rate attests the accuracy and quality of the
      sections.

PMID- 22379371
TI  - Anterolateral thigh flap salvage following failed deep inferior epigastric artery
      perforator breast reconstruction.
AB  - The deep inferior epigastric artery perforator flap is an option for women
      desiring autologous tissue breast reconstruction. If this reconstruction fails,
      other autologous tissue flaps, including the gluteal artery perforator and
      latissimus dorsi flaps, may be used for salvage. The anterolateral thigh (ALT)
      flap offers adequate tissue volume for breast reconstruction, acceptable fat
      quality and a long vascular pedicle. Other advantages include obviating the need
      for intraoperative position changes and harvesting tissue outside of the
      radiation field. Two cases involving ALT flaps used in the setting of deep
      inferior epigastric artery perforator failure are presented with favourable
      results. A review of the anatomy of the ALT flap is included.

PMID- 22379372
TI  - An investigation of the application of laser-assisted indocyanine green
      fluorescent dye angiography in pedicle transverse rectus abdominus myocutaneous
      breast reconstruction.
AB  - BACKGROUND: Pedicle transverse rectus abdominus myocutaneous (pTRAM) flaps remain
      the most common method of autologous tissue breast reconstruction. Using pTRAM
      flaps, complications often arise postoperatively, secondary to inadequate
      circulation. Tissues from distant angiosomes are associated with poorer
      perfusion, but this differs among patients. Many modalities have been used to
      reduce the risk of complications, but none have achieved widespread application.
      The authors believe that laser-assisted indocyanine green fluorescent dye
      angiography (LA-ICGA) can potentially reduce the risk of complications. METHODS:
      In two routine, single-pedicle, ipsilateral pTRAM flaps, LA-ICGA imaging was
      performed following the division of the distal rectus muscle and deep inferior
      epigastric pedicle. The resulting images were used to guide design of the flap
      and debridement. RESULTS: In case 1, good perfusion was observed in zone 1 and
      part of zone 2. In case 2, good perfusion was observed in zone 1 and 50% of zone
      3, with little perfusion in zone 2. In both cases, tissues with poor perfusion
      were debrided before transfer and inset. In both patients, there were no issues
      with wound healing, tissue necrosis or fat necrosis. CONCLUSIONS: The variability
      of perfusion of the pTRAM flap among individuals is well appreciated. LA-ICGA
      helped to determine the limits of good perfusion and, therefore, the limits of
      tissue to be preserved for transfer and inset. This helped to avoid harvesting
      poorly perfused tissue that would have almost certainly experienced necrosis and,
      ultimately, would have reduced the risk of postoperative complications.

PMID- 22379373
TI  - Beyond the borders of keloid formation: A case report.
AB  - The keloid scar is a cutaneous mass characterized by nodular fibroblastic
      proliferation of dermis and a predilection for distinctive anatomical locations.
      However, keloid extension to neighbouring tissue as a nonsyndromic entity has not
      been described. In the present report, a case involving a 48-year-old woman with
      extensive bilateral keloids of the ear lobules and neck following ear piercing is
      presented.

PMID- 22379374
TI  - Incorrect radiographic evaluation after vascularized bone grafting for scaphoid
      fracture or nonunion.
AB  - PURPOSE: The present study is a review of patients with scaphoid non-unions
      treated with a dorsal vascularized bone graft. The study highlights a subset of
      patients incorrectly diagnosed as graft failures. METHODS: A retrospective review
      of patients who received vascularized grafts for scaphoid nonunions was performed
      over a four-year period. The vascularized graft of choice for this group was the
      dorsal radial extensor compartment artery. RESULTS: Five patients from a scaphoid
      fracture group who were treated with vascularized grafts were diagnosed as being
      failures (average of five months). None of these patients had tenderness on
      palpation of the scaphoid, and they were scheduled for revised vascularized
      grafts. All patients at the time of surgery were found to have healed. These
      patients were treated with arthrolysis, resulting in healing and full range of
      motion. CONCLUSIONS: Scaphoid vascularized grafts may have a markedly delayed
      radiographic healing time. Reoperation to perform secondary vascularized
      procedures may result in unnecessary surgery. Early imaging following a scaphoid
      vascularized graft may be inaccurate and may demonstrate a continued nonunion.

PMID- 22379375
TI  - Reflection of a career in paediatrics: A calling becomes a fulfilling profession.

PMID- 22379377
TI  - The Montreal Children's Hospital Feeding Scale: A brief bilingual screening tool
      for identifying feeding problems.
AB  - OBJECTIVE: To establish the psychometric characteristics of a newly developed,
      brief bilingual 14-item parent report tool (The Montreal Children's Hospital
      Feeding Scale [MCH-Feeding Scale]) designed to identify feeding problems in
      children six months to six years of age. METHODS: To establish construct
      validity, 198 mothers of children visiting community paediatrician's offices
      (normative sample) and 174 mothers of children referred to a feeding clinic
      (clinical sample) completed the scale. Test-retest reliability was obtained by
      the re-administration of the MCH-Feeding Scale to 25 children in each sample.
      RESULTS: Excellent construct validity was confirmed when the mean [+/- SD] scores
      of the normative and clinical samples were compared (32.65+/-12.73 versus 60.48+/
      13.04, respectively; P<0.01). Test-retest reliabilities were high for both groups
      (normative r=0.845, clinical r=0.92). CONCLUSION: The MCH-Feeding Scale can be
      used by paediatricians and other health care professionals for quick
      identification of feeding problems.

PMID- 22379376
TI  - Transcutaneous bilirubin measurement at the time of hospital discharge in a
      multiethnic newborn population.
AB  - BACKGROUND: Severe neonatal hyperbilirubinemia continues to occur in healthy
      newborns. Recent guidelines have supported using transcutaneous devices in
      estimating bilirubin levels. Previous studies using these devices are limited.
      METHODS: Newborns requiring serum bilirubin level measurements before hospital
      discharge were recruited prospectively. The agreement between a transcutaneous
      bilirubin (TCB) and total serum bilirubin (TSB) level was assessed. Sensitivity
      analysis was conducted. RESULTS: A total of 430 infants were enrolled.
      Correlation between the values was high (Pearson's correlation coefficient 0.83;
      Lin's concordance coefficient 0.81 [95% CI 0.77 to 0.84]; P<0.001). The mean (+/-
      SD) TSB level was 194+/-60 MUmol/L. The TCB measurement tended to overestimate
      the value (mean difference 12.7), with wide 95% limits of agreement (-52 MUmol/L
      to 77 MUmol/L). Sensitivity and specificity analysis of TCB values allowed
      estimation of clinically important TSB levels. CONCLUSIONS: The TCB correlated,
      but was imprecise in predicting TSB. TCB values can be used at the time of
      discharge to safely plan care for jaundiced infants if the limits of agreement
      are considered and clinical judgment is maintained.

PMID- 22379378
TI  - Toxic metals injuries.

PMID- 22379379
TI  - Lessons learned during implementation of therapeutic hypothermia for neonatal
      hypoxic ischemic encephalopathy in a regional transport program in Ontario.
AB  - BACKGROUND: Therapeutic hypothermia (TH) is the first intervention to
      consistently show improved neurological outcomes in neonates with hypoxic
      ischemic encephalopathy (HIE). Since the recent introduction of TH for HIE in
      many centres, reviews of practices during the implementation of TH in Canada have
      not been published. OBJECTIVE: To determine if eligible neonates are being
      offered TH and to identify any barriers to the effective implementation of TH.
      METHODS: A retrospective review of neonates referred to a regional tertiary
      centre at a gestational age of 35 weeks or more with HIE was conducted. RESULTS:
      Among 41 neonates referred, 29 (71%) were eligible for TH; among eligible
      patients, five were moribund and excluded, and TH was initiated in 16 (67%) of
      the remaining 24. Reasons for not cooling in eight eligible patients included a
      delay in referral (n=5, median age at referral was 14 h) and a failure to
      recognize the severity of HIE (n=3). Among cooled patients, median times were the
      following: 116 min for age at referral; 80 min for time from referral to
      transport team arrival; and 358 min for age at initiation of cooling. Seven (44%)
      patients had cooling initiated after 6 h of age. CONCLUSION: A significant
      proportion of eligible patients were not offered TH, and in many cooled patients,
      initiation of cooling was delayed beyond the recommended 6 h. For eligible
      patients to benefit from TH, it is imperative that all birthing centres be made
      aware that TH is now widely available as an important treatment option, but also
      that TH is a time-sensitive therapy requiring rapid identification and referral.
      In the region studied, for eligible patients, referring hospitals should initiate
      passive cooling before arrival of the transport team. Referring hospitals should
      be prepared to provide early, yet safe initiation of passive cooling by having
      the appropriate equipment, and having staff trained in the use and monitoring of
      rectal temperatures.

PMID- 22379380
TI  - When should nebulized hypertonic saline solution be used in the treatment of
      bronchiolitis?

PMID- 22379381
TI  - Premedication for endotracheal intubation in the newborn infant.
AB  - Endotracheal intubation, a common procedure in newborn care, is associated with
      pain and cardiorespiratory instability. The use of premedication reduces the
      adverse physiological responses of bradycardia, systemic hypertension,
      intracranial hypertension and hypoxia. Perhaps more importantly, premedication
      decreases the pain and discomfort associated with the procedure. All newborn
      infants, therefore, should receive analgesic premedication for endotracheal
      intubation except in emergency situations. Based on current evidence, an optimal
      protocol for premedication is to administer a vagolytic (intravenous [IV]
      atropine 20 MUg/kg), a rapid-acting analgesic (IV fentanyl 3 MUg/kg to 5 MUg/kg;
      slow infusion) and a short-duration muscle relaxant (IV succinylcholine 2 mg/kg).
      Intubations should be performed or supervised by trained staff, with close
      monitoring of the infant throughout.

PMID- 22379382
TI  - Minimum equipment guidelines for paediatric prehospital care.
AB  - Prehospital care has become a well-defined specialty service in Canada, with
      various levels of paramedics providing specialized care to children before their
      arrival to hospital. The equipment required may vary according to the needs of
      the population being served and the level of training of the paramedics who are
      providing the care. The present statement provides a current list of the minimum
      equipment recommended for the provision of prehospital care to neonatal and
      paediatric patients. The most notable change to the present guideline is the
      addition of an automated external defibrillator, which has been added to reflect
      the most recent version of the paediatric advanced life support recommendations
      for the provision of basic life support.

PMID- 22379383
TI  - Emergency department use of oral ondansetron for acute gastroenteritis-related
      vomiting in infants and children.
AB  - Acute gastroenteritis is one of the most common causes of emergency room visits.
      Although it is usually a self-limited infection, vomiting related to this illness
      can cause various degrees of dehydration, leading to intravenous insertion,
      electrolyte abnormalities and/or hospital admission. Ondansetron is a highly
      potent antiemetic drug that is effective in preventing chemotherapy-and radiation
      induced nausea and vomiting with a very low risk of adverse effects. Recently,
      ondansetron has been used to control vomiting related to acute gastroenteritis.
      The present article examines evidence for the use of oral ondansetron for acute
      gastroenteritis-related vomiting in infants and children, and provides a
      recommendation for treatment based on the evidence-based review.

PMID- 22379384
TI  - Implementing the Bedside Paediatric Early Warning System in a community hospital:
      A prospective observational study.
AB  - BACKGROUND: Late transfer of children with critical illness from community
      hospitals undermines the advantages of community-based care. It was hypothesized
      that implementation of the Bedside Paediatric Early Warning System (Bedside PEWS)
      would reduce late transfers. METHODS: A prospective before-and-after study was
      performed in a community hospital 22-bed inpatient paediatric ward. The primary
      outcome, significant clinical deterioration, was a composite measure of
      circulatory and respiratory support before transfer. Secondary outcomes were stat
      calls and resuscitation team calls, paediatrician workload and perceptions of
      frontline staff. RESULTS: Care was evaluated for 842 patient-days before and 2350
      patient-days after implementation. The median inpatient census was 13.
      Implementation of the Bedside PEWS was associated with fewer stat calls to
      paediatricians (22.6 versus 5.1 per 1000 patient-days; P<0.0001), fewer
      significant clinical deterioration events (2.4 versus 0.43 per 1000 patient-days;
      P=0.013), reduced apprehension when calling the physician and no change in
      paediatrician workload. DISCUSSION: Implementation of the Bedside PEWS is
      feasible and safe, and may improve clinical outcomes.

PMID- 22379385
TI  - Amish, mennonite, and hutterite genetic disorder database.

PMID- 22379386
TI  - Tetracha hope 1838 of the Turks and Caicos Islands (coleoptera, carabidae,
      cicindelinae).
AB  - A new species, Tetracha (Neotetracha) naviauxi, and a new subspecies, Tetracha
      (Tetracha) sobrina caicosensis, are described from the Turks and Caicos Islands.
      The key to Tetracha species in Naviaux (2007) is adapted to accommodate Tetracha
      naviauxi. Tetracha sobrina caicosensis is compared to other Caribbean subspecies
      of Tetracha sobrina.

PMID- 22379387
TI  - A re-consideration of the taxonomic status of Nebria lacustris Casey (Coleoptera,
      Carabidae, Nebriini) based on multiple datasets - a single species or a species
      complex?
AB  - This study gathered evidence from principal component analysis (PCA) of
      morphometric data and molecular analyses of nucleotide sequence data for four
      nuclear genes (28S, TpI, CAD1, and Wg) and two mitochondrial genes (COI and 16S),
      using parsimony, maximum likelihood, and Bayesian methods. This evidence was
      combined with morphological and chorological data to re-evaluate the taxonomic
      status of Nebria lacustris Casey sensu lato. PCA demonstrated that both body size
      and one conspicuous aspect of pronotal shape vary simultaneously with elevation,
      latitude, and longitude and served to distinguish populations from the southern
      Appalachian highlands, south of the French Broad, from all other populations.
      Molecular analyses revealed surprisingly low overall genetic diversity within
      Nebria lacustris sensu lato, with only 0.39% of 4605 bp varied in the
      concatenated dataset. Evaluation of patterns observed in morphological and
      genetic variation and distribution led to the following taxonomic conclusions:
      (1) Nebria lacustris Casey and Nebria bellorum Kavanaugh should be considered
      distinct species, which is a NEW STATUS for Nebria bellorum. (2) No other
      distinct taxonomic subunits could be distinguished with the evidence at hand, but
      samples from northeastern Iowa, in part of the region known as the "Driftless
      Zone", have unique genetic markers for two genes that hint at descent from a
      local population surviving at least the last glacial advance. (3) No morphometric
      or molecular evidence supports taxonomic distinction between lowland populations
      on the shores of Lake Champlain and upland populations in the adjacent Green
      Mountains of Vermont, despite evident size and pronotal shape differences between
      many of their members.

PMID- 22379388
TI  - Phylogeny of minute carabid beetles and their relatives based upon DNA sequence
      data (Coleoptera, Carabidae, Trechitae).
AB  - The phylogeny of ground beetles of supertribe Trechitae is inferred using DNA
      sequences of genes that code for 28S ribosomal RNA, 18S ribosomal RNA, and
      wingless. Within the outgroups, austral psydrines are inferred to be
      monophyletic, and separate from the three genera of true Psydrina (Psydrus,
      Nomius, Laccocenus); the austral psydrines are formally removed from Psydrini and
      are treated herein as their own tribe, Moriomorphini Sloane. All three genes
      place Gehringia with Psydrina. Trechitae is inferred to be monophyletic, and
      sister to Patrobini.Within trechites, evidence is presented that Tasmanitachoides
      is not a tachyine, but is instead a member of Trechini. Perileptus is a member of
      subtribe Trechodina. Against Erwin's hypothesis of anillines as a polyphyletic
      lineage derived from the tachyine genus Paratachys, the anillines sampled are
      monophyletic, and not related to Paratachys. Zolini, Pogonini, Tachyina, and
      Xystosomina are all monophyletic, with the latter two being sister groups. The
      relationships of the subtribe Bembidiina were studied in greater detail. Phrypeus
      is only distantly related to Bembidion, and there is no evidence from sequence
      data that it belongs within Bembidiina. Three groups that have been recently
      considered to be outside of the large genus Bembidion are shown to be derived
      members of Bembidion, related to subgroups: Cillenus is related to the Ocydromus
      complex of Bembidion, Zecillenus is related to the New Zealand subgenus
      Zeplataphus, and Hydrium is close to subgenus Metallina. The relationships among
      major lineages of Trechitae are not, however, resolved with these data.

PMID- 22379389
TI  - Rediscovery of Bembidion (Lymnaeum) nigropiceum (Marsham) (= puritanum Hayward)
      in Massachusetts, with remarks on biology and habitat (Coleoptera, Carabidae,
      Bembidiini).
AB  - Bembidion (Lymnaeum) nigropiceum (Marsham) (=puritanum Hayward), a European
      species introduced into Massachusetts but presumed not to have become
      established, has been rediscovered during the Boston Harbor Islands All Taxa
      Biodiversity Inventory undertaken by the Museum of Comparative Zoology and the
      National Park Service. A summary is presented of treatment of this species in
      North America. Data on specimens collected are presented, along with observations
      on habitat and biology. Some speculations are presented about its highly
      specialized habitat in the gravel pushed up by high tide, which may act as a food
      trapping sieve. A few words are included about future actions needed to resolve
      questions of distribution and behavior.

PMID- 22379390
TI  - Wing-dimorphism and population expansion of Pterostichus melanarius (Illiger,
      1798) at small and large scales in central Alberta, Canada (Coleoptera,
      Carabidae, Pterostichini).
AB  - A study spanning ten years revealed changes in wing-morph ratios corroborating
      the hypothesis that the wing-dimorphic introduced carabid, Pterostichus
      melanarius Ill.,is spreading through flight, from the city of Edmonton, Canada
      and establishing populations in natural aspen forest of more rural areas 45-50 km
      to the East. Comparison of wing-morph ratios between Pterostichus melanarius and
      the native wing dimorphic species Agonum retractum LeConte suggests that the
      spatial variation in ratios for Pterostichus melanarius does not reflect
      underlying environmental variation, but instead the action of selective forces on
      this wing-dimorphic species. About ten years after its earliest detection in some
      rural sites the frequency of macropterous individuals in Pterostichus melanarius
      has decreased c. five-fold, but it is still above the level seen in European
      populations in which the two wing-morphs are thought to exist in equilibrium.
      Pterostichus melanarius is expanding its range in native aspen forest much faster
      than three other introduced species Clivina fossor L.), Carabus granulatus O.F.
      Mullerand Clivina fossor L also encountered in this study. The two Carabus
      species are flightless, but Carabus fossor can be dimorphic. Although these four
      non-native ground beetle species comprise >85% of the carabids collected at sites
      in urban Edmonton, activity-density of native carabids was similar across the
      urban-rural gradient, suggesting little direct impact of introduced species on
      the local abundance of native species. In a second study conducted at a smaller
      scale near George Lake, Alberta, macropterous individuals of Pterostichus
      melanarius have penetrated furthest and most rapidly into native aspen forest.
      Furthermore, the percentage of micropterous individuals has increased markedly in
      areas first colonized a decade previously. Overall, these studies support the
      idea that macropterous beetles in wing-d dimorphic species are important
      vanguards for early colonization of unexploited territory, but that flightless
      individuals replace the flying morph relatively rapidly once populations are
      established.

PMID- 22379391
TI  - Evolutionary systems biology.

PMID- 22379392
TI  - Highly efficient proteolysis accelerated by electromagnetic waves for Peptide
      mapping.
AB  - Proteomics will contribute greatly to the understanding of gene functions in the
      post-genomic era. In proteome research, protein digestion is a key procedure
      prior to mass spectrometry identification. During the past decade, a variety of
      electromagnetic waves have been employed to accelerate proteolysis. This review
      focuses on the recent advances and the key strategies of these novel proteolysis
      approaches for digesting and identifying proteins. The subjects covered include
      microwave-accelerated protein digestion, infrared-assisted proteolysis,
      ultraviolet-enhanced protein digestion, laser-assisted proteolysis, and future
      prospects. It is expected that these novel proteolysis strategies accelerated by
      various electromagnetic waves will become powerful tools in proteome research and
      will find wide applications in high throughput protein digestion and
      identification.

PMID- 22379393
TI  - Microbial metabolomics.
AB  - Microbial metabolomics constitutes an integrated component of systems biology. By
      studying the complete set of metabolites within a microorganism and monitoring
      the global outcome of interactions between its development processes and the
      environment, metabolomics can potentially provide a more accurate snap shot of
      the actual physiological state of the cell. Recent advancement of technologies
      and post-genomic developments enable the study and analysis of metabolome. This
      unique contribution resulted in many scientific disciplines incorporating
      metabolomics as one of their "omics" platforms. This review focuses on
      metabolomics in microorganisms and utilizes selected topics to illustrate its
      impact on the understanding of systems microbiology.

PMID- 22379394
TI  - The -omics Era- Toward a Systems-Level Understanding of Streptomyces.
AB  - Streptomyces is a group of soil bacteria of medicinal, economic, ecological, and
      industrial importance. It is renowned for its complex biology in gene regulation,
      antibiotic production, morphological differentiation, and stress response. In
      this review, we provide an overview of the recent advances in Streptomyces
      biology inspired by -omics based high throughput technologies. In this post
      genomic era, vast amounts of data have been integrated to provide significant new
      insights into the fundamental mechanisms of system control and regulation
      dynamics of Streptomyces.

PMID- 22379395
TI  - Proteases in malaria parasites - a phylogenomic perspective.
AB  - Malaria continues to be one of the most devastating global health problems due to
      the high morbidity and mortality it causes in endemic regions. The search for new
      antimalarial targets is of high priority because of the increasing prevalence of
      drug resistance in malaria parasites. Malarial proteases constitute a class of
      promising therapeutic targets as they play important roles in the parasite life
      cycle and it is possible to design and screen for specific protease inhibitors.
      In this mini-review, we provide a phylogenomic overview of malarial proteases. An
      evolutionary perspective on the origin and divergence of these proteases will
      provide insights into the adaptive mechanisms of parasite growth, development,
      infection, and pathogenesis.B.

PMID- 22379398
TI  - Gerald a. Isenberg, m.d.

PMID- 22379397
TI  - Genetics of recurrent vertigo and vestibular disorders.
AB  - We present recent advances in the genetics of recurrent vertigo, including
      familial episodic ataxias, migraneous vertigo, bilateral vestibular hypofunction
      and Meniere's disease.Although several vestibular disorders are more common
      within families, the genetics of vestibulopathies is largely not known. Genetic
      loci and clinical features of familial episodic ataxias have been defined in
      linkage disequilibrium studies with mutations in neuronal genes KCNA1 and
      CACNA1A. Migrainous vertigo is a clinical disorder with a high comorbidity within
      families much more common in females with overlapping features with episodic
      ataxia and migraine. Bilateral vestibular hypofunction is a heterogeneous
      clinical group defined by episodes of vertigo leading to progressive loss of
      vestibular function which also can include migraine. Meniere's disease is a
      clinical syndrome characterized by spontaneous episodes of recurrent vertigo,
      sensorineural hearing loss, tinnitus and aural fullness and familial Meniere's
      disease in around 10-20% of cases. An international collaborative effort to
      define the clinical phenotype and recruiting patients with migrainous vertigo and
      Meniere's disease is ongoing for genome-wide association studies.

PMID- 22379399
TI  - Anorectal disease.

PMID- 22379396
TI  - Life or death? A physiogenomic approach to understand individual variation in
      responses to hemorrhagic shock.
AB  - Severe hemorrhage due to trauma is a major cause of death throughout the world.
      It has often been observed that some victims are able to withstand hemorrhage
      better than others. For decades investigators have attempted to identify
      physiological mechanisms that distinguish survivors from nonsurvivors for the
      purpose of providing more informed therapies. As an alternative approach to
      address this issue, we have initiated a research program to identify genes and
      genetic mechanisms that contribute to this phenotype of survival time after
      controlled hemorrhage. From physiogenomic studies using inbred rat strains, we
      have demonstrated that this phenotype is a heritable quantitative trait, and is
      therefore a complex trait regulated by multiple genes. Our work continues to
      identify quantitative trait loci as well as potential epigenetic mechanisms that
      might influence survival time after severe hemorrhage. Our ultimate goal is to
      improve survival to traumatic hemorrhage and attendant shock via regulation of
      genetic mechanisms and to provide knowledge that will lead to genetically
      informed personalized treatments.

PMID- 22379400
TI  - Hemorrhoids.
AB  - Hemorrhoid disease is the most common reason patients seek evaluation by a colon
      and rectal surgeon. The majority of hemorrhoids can be managed nonoperatively
      with medical management or office-based procedures. The authors review the
      anatomy, pathophysiology, presentation, and management of hemorrhoids.

PMID- 22379401
TI  - Anorectal infection: abscess-fistula.
AB  - Anorectal abscess and fistula are among the most common diseases encountered in
      adults. Abscess and fistula should be considered the acute and chronic phase of
      the same anorectal infection. Abscesses are thought to begin as an infection in
      the anal glands spreading into adjacent spaces and resulting in fistulas in ~40%
      of cases. The treatment of an anorectal abscess is early, adequate, dependent
      drainage. The treatment of a fistula, although surgical in all cases, is more
      complex due to the possibility of fecal incontinence as a result of
      sphincterotomy. Primary fistulotomy and cutting setons have the same incidence of
      fecal incontinence depending on the complexity of the fistula. So even though the
      aim of a surgical procedure is to cure a fistula, conservative management short
      of major sphincterotomy is warranted to preserve fecal incontinence. However,
      trading radical surgery for conservative (nonsphincter cutting) procedures such
      as a draining seton, fibrin sealant, anal fistula plug, endorectal advancement
      flap, dermal island flap, anoplasty, and LIFT (ligation of intersphincteric
      fistula tract) procedure all result in more recurrence/persistence requiring
      repeated operations in many cases. A surgeon dealing with fistulas on a regular
      basis must tailor various operations to the needs of the patient depending on the
      complexity of the fistula encountered.

PMID- 22379403
TI  - Anal warts and anal intradermal neoplasia.
AB  - For the last five millennia we have been dealing with the annoyance of verrucas.
      Anogenital human papillomavirus (HPV) infection is the most common sexually
      transmitted disease in the United States and is increasing in incidence. As in
      other gastrointestinal conditions, HPV infection can lead to a stepwise
      transition from normal cells to dysplastic cells and then to invasive anal
      cancer. Knowledge of the natural history of HPV infection, risk factors,
      diagnostic tools, and therapeutic methods gives us the tools to adequately
      prevent, evaluate, treat, and counsel our patients. In this review, the authors
      detail the diagnosis, management, and treatment of anal condyloma and anal
      intraepithelial neoplasia with a focus on prevention, early detection, and
      treatment using current data and technology.

PMID- 22379404
TI  - Rectal prolapse.
AB  - Rectal prolapse is a condition that usually requires surgical intervention to
      correct. Abdominal and perineal approaches are well described in the literature.
      Abdominal approaches have traditionally been reserved for young healthy patients,
      but this has been challenged by perineal approaches with excellent outcomes.
      Laparoscopic techniques have been shown to be effective and equivalent to
      traditional laparotomy techniques.

PMID- 22379402
TI  - Anal fissure.
AB  - Anal fissure is one of the most common anorectal problems. Anal fissure is
      largely associated with high anal sphincter pressures and most treatment options
      are based on reducing anal pressures. Conservative management, using increased
      fiber and warm baths, results in healing of approximately half of all anal
      fissures. In fissures that fail conservative care, various pharmacologic and
      surgical options offer satisfactory cure rates. Lateral internal sphincterotomy
      remains the gold standard for definitive management of anal fissure. This review
      outlines the key points in the presentation, pathophysiology, and management of
      anal fissure.

PMID- 22379405
TI  - Pilonidal disease.
AB  - Pilonidal disease presents many therapeutic challenges to surgeons throughout the
      world. Its varied clinical presentations necessitate a wide range of treatments,
      thus underscoring the need to tailor the treatment to the patient and the
      severity of disease. Recent studies confirm the efficacy of smaller, more
      conservative operations for appropriate indications. When flap closures are
      performed, every attempt should be directed to placing sutures off (lateral) to
      the midline gluteal cleft. Meticulous attention to the details of immediate and
      long-term postoperative care is paramount.

PMID- 22379406
TI  - Neoplasms of anal canal and perianal skin.
AB  - Tumors of the anus and perianal skin are rare. Their presentation can vary and
      often mimics common benign anal pathology, thereby delaying diagnosis and
      appropriate and timely treatment. The anatomy of this region is complex because
      it represents the progressive transition from the digestive system to the skin
      with many different co-existing types of cells and tissues. Squamous cell
      carcinoma of the anal canal is the most frequent tumor found in the anal and
      perianal region. Less-frequent lesions include Bowen's and Paget's disease, basal
      cell carcinoma, melanoma, and adenocarcinoma. This article aims to review the
      clinical presentation, diagnostic evaluation, and treatment options for neoplasms
      of the anal canal and perianal skin.

PMID- 22379407
TI  - Fecal incontinence: etiology, evaluation, and treatment.
AB  - Fecal incontinence is a debilitating problem facing ~2.2% of the U.S. general
      population over 65 years of age. Etiologic factors include traumatic, neurologic,
      congenital, and iatrogenic. Most commonly, obstetric trauma causes fecal
      incontinence as well as poorly performed anorectal surgery or pelvic radiation.
      Several severity scores and quality of life indexes have been developed to
      quantify incontinent symptoms. There are several nonsurgical and surgical options
      for the treatment of fecal incontinence. Biofeedback is among the most successful
      nonoperative strategies. Depending on the cause, anal sphincter repair,
      artificial bowel sphincter, and sacral nerve stimulation are used to treat fecal
      incontinence with some success. Unfortunately, fecal incontinence is an extremely
      difficult problem to manage: there has not been one, single treatment option that
      has proven to be both safe and effective in long-term studies.

PMID- 22379408
TI  - Hidradenitis suppurativa and pruritus ani.
AB  - Hidradenitis suppurativa (HS) is a chronic debilitating disorder that can affect
      any areas bearing apocrine glands. Perineal HS is associated with high morbidity
      compared with other anatomic regions. Early-stage disease may mimic various other
      forms of cutaneous disorders, but as HS progresses pathognomonic skin changes
      occur. Clinical stage can guide the therapeutic approach, but the lowest
      recurrence rate is obtained by removing all involved skin and subcutaneous fat.
      Pruritus ani is a complex disease with a multitude of etiologies. Its management
      can be frustrating and disappointing for the patient and doctor alike. The key is
      to start with simple treatment options focusing on perianal hygiene and avoidance
      of the most common offending foods and beverages. If these measures fail, topical
      medications should be attempted before graduating to perianal injections of
      methylene blue as a last resort.

PMID- 22379411
TI  - Palliative care: staying alive as long as we live.

PMID- 22379410
TI  - Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy
      metabolism.
AB  - Kinetic models of metabolism require detailed knowledge of kinetic parameters.
      However, due to measurement errors or lack of data this knowledge is often
      uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei
      is a particularly well analysed example of a quantitative metabolic model, but so
      far it has been studied with a fixed set of parameters only. Here we evaluate the
      effect of parameter uncertainty. In order to define probability distributions for
      each parameter, information about the experimental sources and confidence
      intervals for all parameters were collected. We created a wiki-based website
      dedicated to the detailed documentation of this information: the SilicoTryp wiki
      (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected
      in the wiki, we then assigned probability distributions to all parameters of the
      model. This allowed us to sample sets of alternative models, accurately
      representing our degree of uncertainty. Some properties of the model, such as the
      repartition of the glycolytic flux between the glycerol and pyruvate producing
      branches, are robust to these uncertainties. However, our analysis also allowed
      us to identify fragilities of the model leading to the accumulation of 3
      phosphoglycerate and/or pyruvate. The analysis of the control coefficients
      revealed the importance of taking into account the uncertainties about the
      parameters, as the ranking of the reactions can be greatly affected. This work
      will now form the basis for a comprehensive Bayesian analysis and extension of
      the model considering alternative topologies.

PMID- 22379412
TI  - Time for better integration of oncology and palliative care.

PMID- 22379413
TI  - Perspectives from the other side: a physician and cancer survivor.
AB  - ASCO has made great strides to integrate palliative care into the comprehensive
      care model. However, much work remains to ensure that all patients, whether
      receiving curative or palliative therapy, have a good quality of life.

PMID- 22379415
TI  - Building on Individual, State, and Federal Initiatives for Advance Care Planning,
      an Integral Component of Palliative and End-of-Life Cancer Care.
AB  - Federal and state provisions for advance care planning-the process by which
      patients, families, and medical professionals plan for future and, in particular,
      end-of-life care-continue to receive attention. Such planning remains an integral
      component of palliative care, complementing the recognition and treatment of pain
      and other symptoms that patients with advanced malignancies and their families
      encounter. Historically, advance care planning interventions (particularly those
      involving advance directives) have been unable to consistently demonstrate
      positive outcomes for patients with life-threatening illnesses. However, more
      recent literature, including that on patients with cancer, illustrates that both
      patients and caregivers report improved quality of life and less distress after
      discussions with their health care teams about end-of-life care. Herein, we
      discuss recent federal and state public policy that focuses on advance care
      planning, suggesting the promise for care delivery improvements and the means by
      which existing barriers might be surmounted. These care delivery issues apply to
      several disease states but are particularly pertinent to the adult oncology
      setting.

PMID- 22379414
TI  - Integration of palliative medicine into routine oncological care: what does the
      evidence show us?
AB  - Palliative medicine is now a recognized medical subspecialty. The goal of
      palliative medicine is to prevent and relieve suffering, and to support the best
      possible quality of life for patients and their families, regardless of the stage
      of their illness.(1) Typically, palliative medicine teams consist of multiple
      disciplines (such as physicians, advanced practice nurses, social workers, and
      chaplains) to address several domains of the patient experience. Medical
      oncologists have routinely provided palliative care to their patients along with
      antineoplastic therapy. Nevertheless, there is a recognized need for an
      improvement in palliative care delivery to the patient with advanced cancer. This
      narrative review outlines recent clinical trials of palliative care being
      integrated into routine oncological care.

PMID- 22379416
TI  - Taking care: community, family, and dying in place.
AB  - Medicine, and cancer medicine particularly, exists on the interface of the human
      condition and science. The profession is distinguished by its human side, yet it
      is science that informs and complements patient interaction.

PMID- 22379417
TI  - Documentation and discussion of preferences for care among patients with advanced
      cancer.
AB  - PURPOSE: We sought to describe the documentation, frequency, and timing of
      discussions about patient preferences for care and to examine patterns of
      palliative care and hospice use among patients with advanced cancer. METHODS: We
      prospectively abstracted the medical records of 118 patients receiving care at a
      Veterans Administration (VA) facility from diagnosis of stage IV disease to 12
      months postdiagnosis or death. We used univariate statistics to describe the type
      and frequency of documentation of patient preferences and palliative care/hospice
      referral. We calculated the time from diagnosis to the first documentation of
      preferences and the time from first documentation to death. We compared
      documentation of patient preferences between decedents and nondecedents using
      chi(2) tests. RESULTS: The majority of patients (81%) had some documentation of
      their care preferences recorded, although decedents were significantly more
      likely to have had their preferences documented than nondecedents (96% v 60%; P <
      .000). Most (53%) patients did not have a formal advance directive documented in
      the medical record. The mean time from diagnosis to the first documentation of
      preferences was approximately 2 months. More than half of all patients (53%) and
      almost three-quarters of decedents (73%) had a palliative care consultation.
      CONCLUSION: Despite high rates of preference documentation, there remains room
      for improvement. Providers may need to be helped to identify patients earlier in
      their trajectory for appropriate palliative care services, and future work should
      focus on developing useful alternatives to advance directives for adequately
      documenting patient preferences.

PMID- 22379418
TI  - Palliative care in the outpatient oncology setting: evaluation of a practical set
      of referral criteria.
AB  - BACKGROUND: The National Comprehensive Cancer Network's (NCCN) palliative care
      (PC) guidelines recommend screening all patients for PC issues at the first visit
      with their oncologist and at subsequent, clinically relevant times. Criteria for
      referral to a PC specialist are also part of the guideline. We evaluated the
      feasibility of screening for PC needs in outpatients attending one GI oncology
      practice specializing in colorectal cancer and neuroendocrine tumors. METHODS:
      All patients attending clinic during a 3-week period were screened by the office
      practice nurse (OPN). A one-page screening tool based on the NCCN guidelines was
      developed, giving a score from 0 to 13. The OPN also evaluated the NCCN referral
      criteria. RESULTS: There were 152 clinic visits by 125 patients during the
      surveillance period; 119 were screened. Median age was 61 years; half were male.
      Eighty percent had colorectal cancer, and two thirds had advanced disease.
      Screening took approximately 3 to 5 minutes per patient. Depending on the PC
      definition used, between 7% and 17% of patients screened positive; all met the
      NCCN referral criteria. Psychosocial distress was commoner than physical
      symptoms. The maximum screening score was 8. A cut point of 5 had the best
      predictive value for specialist referral, and would result in 13% patients having
      PC consultations. CONCLUSION: Screening identified 7% to 17% of patients in this
      busy clinic as having PC issues and 13% who might benefit from specialist
      referral. But even this simple method adds considerably to the clinic workload,
      so the benefits of implementing routine screening need to be carefully evaluated.

PMID- 22379419
TI  - Multimorbidity: an issue of growing importance for oncologists.
AB  - As our population ages, more are afflicted with chronic conditions. Likewise, as
      more patients survive the diagnosis of cancer, they are likely to experience the
      sequelae of cancer treatment in the context of other coexisting medical
      conditions. Oncologists can expect that more than half of the patients they see
      who are older than 65 years will have at least one other meaningful chronic
      condition that may affect their treatment regimen. Multimorbidity can increase
      both treatment and illness burden and influence the benefit and burden of cancer
      treatment. Recognition of the impact of multiple co-occurring conditions on a
      patient's cancer care plan and development of strategies to address the
      challenges associated with multimorbidity will enable oncologists to provide
      higher quality, patient-centered care. Increased efforts should be focused on
      educating clinical providers to practice the collaborative, team-based care
      required by these patients. Finally, research is desperately needed to guide
      oncologists and other providers in the unique management issues presented by
      patients with multimorbidity.

PMID- 22379420
TI  - Longitudinal patient-reported performance status assessment in the cancer clinic
      is feasible and prognostic.
AB  - PURPOSE: Performance status is prognostic in oncology and palliative care
      settings. Traditionally clinician rated, it is often inconsistently collected,
      recorded, and measured, thereby limiting its utility. Patient-reported strategies
      are increasingly used for routine symptom and quality of life assessment in the
      clinic, and may be useful for tracking performance status. METHODS: Tablet
      personal computers were used to collect patient-reported reviews of systems via
      the Patient Care Monitor (PCM) v2.0 for 86 patients with advanced lung cancer.
      Relevant subscales included the PCM Impaired Performance and Impaired Ambulation
      scales. Trained nurse clinicians measured performance status using traditional
      Karnofsky and Eastern Cooperative Oncology Group (ECOG) instruments. Correlation
      coefficients were used to compare performance status scales, and survival
      analysis was performed by Cox proportional hazards modeling. RESULTS: All four
      performance status scales demonstrated excellent internal consistency and
      convergent validity. Initial KPS and ECOG scores were statistically correlated
      with survival, whereas PCM scores showed a nonsignificant trend in this
      direction. Change in PCM Impaired Performance over time was statistically
      correlated with survival (hazard ratio = 1.62, P = .046), whereas the other three
      performance status measures were not statistically prognostic. CONCLUSION:
      Patient-reported performance status as measured by PCM v2.0 is at least as
      reliable as KPS or ECOG. The enhanced resolution provided by this patient
      reported method allows for the detection of clinically meaningful changes in
      trajectory over time, potentially serving as an early-warning system to trigger
      clinical interventions. Further study is needed to test these findings on a
      larger scale.

PMID- 22379421
TI  - Linking palliative care and oncology practice: performance status as a common
      thread.

PMID- 22379422
TI  - Palliative care needs of patients with cancer living in the community.
AB  - PURPOSE: With improved effectiveness of early detection and treatment, many
      patients with cancer are now living with advanced disease and associated
      symptoms. As cancer becomes a chronic illness, adequate attention to patients'
      symptoms and psychosocial needs in the community setting requires positioning of
      palliative care alongside cancer care. This article describes the current
      palliative care needs of a population of community-dwelling patients with
      advanced cancer who are not yet ready for transition to hospice. METHODS: This
      secondary analysis used quality-monitoring data collected in three community
      based palliative care organizations. Analyses focused on people with cancer
      related diagnoses who were receiving palliative care during 2008 to 2011.
      RESULTS: The analytic data set included 4,980 people, 10% of whom had cancer.
      Median age was 71 years. Forty-eight percent had been hospitalized at least once
      in the 6 months before palliative care referral. Forty-nine percent had a
      Palliative Performance Score (PPS) of 40% to 60%; 40% had PPS <= 30%. Although
      81% had an estimated prognosis of <= 6 months, 58% were expected to live weeks to
      months. Thirty-three percent had no identified healthcare surrogate; 59% had no
      do-not-resuscitate order despite declining functional status and limited
      prognosis. Ninety-five percent reported >= 1 symptom, and 67% reported >= 3
      symptoms; a substantial proportion did not receive treatment for symptoms.
      CONCLUSIONS: Patients referred to community-based palliative care experience
      multiple often-severe symptoms that have been insufficiently addressed. They tend
      to have declining performance status. Earlier palliative care intervention could
      improve outcomes but will require delivery models that better coordinate
      inpatient/outpatient oncology and community-based palliative care.

PMID- 22379423
TI  - Malpractice suits and physician apologies in cancer care.

PMID- 22379424
TI  - Commentary: physician apologies for adverse outcomes-beware the minefields of mea
      culpa.

PMID- 22379425
TI  - Antiemetics: american society of clinical oncology clinical practice guideline
      update.
AB  - ASCO's update to its antiemetics guideline now includes an evaluation of evidence
      on complementary antiemetic therapy.

PMID- 22379426
TI  - Commentary: should cost and comparative value of treatments be considered in
      clinical practice guidelines?

PMID- 22379427
TI  - Improving quality and addressing the rising costs of cancer care: two birds, one
      stone.
AB  - The authors discuss the current state of Medicare reimbursement policy and
      outline their recently published model to link improvements in the quality of
      cancer care to reductions in overall cost.

PMID- 22379428
TI  - Quality of care in non-small-cell lung cancer: findings from 11 oncology
      practices in Florida.
AB  - BACKGROUND: Limited data on the quality of care in non-small-cell lung cancer
      (NSCLC) are available. This study aims to assess the quality of care in NSCLC
      among 11 medical oncology practices in Florida and to explore the impact of
      practice volume on care. METHODS: Clinical guidelines and existing indicators
      were reviewed, and an expert survey was conducted to identify a set of process
      based quality of care indicators (QI). Medical records of new patients with NSCLC
      seen in 2006 were retrospectively reviewed for the adherence to these QIs.
      RESULTS: We reviewed the compliance with a set of 11 QIs (four general and seven
      NSCLC specific) among 531 patients. The patient median age was 68 years; 51% were
      male, and 49% had advanced NSCLC. The median adherence rates to general QIs and
      NSCLC-specific QIs were 95% (range 69% to 99%) and 69% (range 29% to 91%),
      respectively. We identified three main areas of deficiencies: chemotherapy
      consenting (69%), brain staging for stage III NSCLC (59%), and performance status
      assessment for advanced stages (42%). Significant variation in the adherence
      rates across practice sites was observed in five of 11 QIs. CONCLUSION: On the
      basis of this data set of participating institutions in Florida, several areas in
      the care of patients with NSCLC were identified as targets for future quality
      improvement efforts.

PMID- 22379429
TI  - AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice
      Platform.
AB  - PURPOSE: Present the design and initial evaluation of a unique, Web-enabled
      platform for the development of a community of practice around issues of oncology
      clinical trial accrual. METHODS: The National Cancer Institute (NCI) conducted
      research with oncology professionals to identify unmet clinical trial accrual
      needs in the field. In response, a comprehensive platform for accrual resources,
      AccrualNet, was created by using an agile development process, storyboarding, and
      user testing. Literature and resource searches identified relevant content to
      populate the site. Descriptive statistics were tracked for resource and site
      usage. Use cases were defined to support implementation. RESULTS: ACCRUALNET HAS
      FIVE LEVELS: (1) clinical trial macrostages (prestudy, active study, and
      poststudy); (2) substages (developing a protocol, selecting a trial, preparing to
      open, enrolling patients, managing the trial, retaining participants, and lessons
      learned); (3) strategies for each substage; (4) multiple activities for each
      strategy; and (5) multiple resources for each activity. Since its launch,
      AccrualNet has had more than 45,000 page views, with the Tools & Resources,
      Conversations, and Training sections being the most viewed. Total resources have
      increased 69%, to 496 items. Analysis of articles in the site reveals that 22%
      are from two journals and 46% of the journals supplied a single article. To date,
      there are 29 conversations with 43 posts. Four use cases are discussed.
      CONCLUSION: AccrualNet represents a unique, centralized comprehensive-solution
      platform to systematically capture accrual knowledge for all stages of a clinical
      trial. It is designed to foster a community of practice by encouraging users to
      share additional strategies, resources, and ideas.

PMID- 22379430
TI  - Achieving Exemplary Attributes With AccrualNet.
AB  - The AccrualNet Web site is a helpful compilation of resources for sites aspiring
      to improve trial accrual.

PMID- 22379431
TI  - Advance care planning with your patients.
AB  - Studies have shown that patients want their doctor to talk to them about their
      advance care plans, and they want that discussion sooner rather than later.

PMID- 22379432
TI  - Perilunate injuries.
AB  - Perilunate dislocations and fracture dislocations are most often a result of high
      energy trauma, exerting an axial load with hyperextension and ulnar deviation of
      the wrist, along with intercarpal supination. Early treatment of perilunate
      injuries is necessary to optimize the clinical outcome. Although closed
      management has been the more commonly reported treatment for perilunate injuries,
      the current consensus is that anatomic restoration of carpal alignment has better
      results. The combined dorsal-volar approach offers the advantages of both
      approaches and is the preferred choice for the authors since it allows assessment
      of all the injured structures. The surgical techniques to restore carpal
      alignment and repair the scapholunate interosseous ligament are discussed.
      Current literature regarding treatment and prognosis is also included.

PMID- 22379433
TI  - Surgical approaches to the distal radius.
AB  - INTRODUCTION: Fractures of the distal radius are among the most common fractures
      seen. They encompass a myriad of presentations and fracture patterns that often
      benefit from various open reduction and internal fixation techniques-including
      volar plating, dorsal plating, radial plating, intramedullary nailing, and
      fragment-specific fixation. In order to obtain optimal reduction of these
      fractures, surgeons require a thorough understanding of the anatomy and various
      surgical exposures. ANATOMY: The distal radius is surrounded by a soft tissue
      envelope rich in vascularity and cutaneous innervation. The osseous surface
      consists of two articular surfaces and three cortical sides covered almost
      entirely by soft tissue. SURGICAL APPROACHES: Approaches to the distal radius can
      be broadly divided into volar, radial, and dorsal. Visualization of the articular
      surface can be accomplished best arthroscopically. Arthroscopy can be performed
      alone or in conjunction with other open approaches to the distal radius. SUMMARY:
      This article will review the pertinent anatomy and various surgical approaches in
      order to facilitate the surgeon's ability to safely expose a distal radius
      fracture.

PMID- 22379435
TI  - Comminuted radial head fractures treated with pyrocarbon prosthetic replacement.
AB  - PURPOSE: We had evaluated our experience in the treatment of displaced and
      comminuted radial head fractures with pyrocarbon radial head prosthesis. METHODS:
      From May 2003 to July 2008, radial head prostheses were performed in 47 patients.
      There were 29 female and 18 male with mean age 51 (34-70 years). The follow-up
      was a mean of 48 (12-60 months). Fractures of the radial head have been
      classified by Hotchkiss. The indications for a radial head replacement were type
      III fractures in 27 cases, type IV fractures in ten cases, comminuted radial
      fracture associated with disruption of the medial collateral ligament in three
      cases, Monteggia variant in five cases, and Essex-Lopresti in two cases.
      Functional outcomes were assessed by visual analog scales (VAS) of pain, joint
      motion and stability, and using the Mayo Elbow Performance Index. RESULTS: The
      mean VAS score for elbow pain was 1 (0.5-2.1). Patients showed an average arc of
      motion from 6 degrees  to 140 degrees , with 75 degrees  of pronation and 67
      degrees  of supination. By using the Mayo Elbow Performance Index, 42 patients
      had good/excellent results, with three fair and two poor outcomes. Complications
      were two implant dislocations, one elbow stiffness, one dissociation of the
      implant, one stem rupture, and two posterior interosseous nerve palsy that
      recovered from 5 to 8 weeks. We had not seen persistent instability, infection,
      synostosis, severe degenerative changes, or impingement. CONCLUSIONS: The
      treatment of comminuted radial head fracture with pyrocarbon implant usually
      gives an optimal result depending on the severity of the initial injury and the
      presence of associated lesions. The size of the prosthesis is often
      overestimated, causing restriction in motion due to impingement, overstuffing, or
      dislocations.

PMID- 22379434
TI  - Hand and foot abnormalities associated with genetic diseases.
AB  - INTRODUCTION: The small bones and soft tissues of the hands and feet can be
      affected by systemic disorders, and frequently, the findings are quite unique and
      virtually diagnostic for some genetic or metabolic disorders. MATERIALS AND
      METHODS: Photographs and imaging studies for the hands and feet are available in
      a digitized system, which has been approved by our hospital institutional review
      board. Examination of these and their description can establish a relationship
      with some degree of certainty to a series of highly variable and uncommon
      clinical disorders. RESULTS: Description of the clinical, physiologic and genetic
      characteristics, and illustrations of hand and foot abnormalities are provided
      for an array of diseases, including Ellis-van Creveld syndrome, fibrodysplasia
      ossificans progressiva, achondroplasia, Kniest dysplasia, pseudo- and pseudo
      pseudohypoparathyroidism, acromegaly, nail-patella syndrome, Marfan's disease,
      cartilage-hair hypoplasia, and several forms of mucopolysaccharidosis.
      CONCLUSIONS: The findings support the concept that many genetic disorders can
      often be diagnosed by clinical and imaging examination of the patient's hands and
      feet.

PMID- 22379436
TI  - Repair of acute and chronic distal biceps tendon ruptures using the EndoButton.
AB  - There are many ways to repair distal biceps tendon ruptures with no outcome
      studies demonstrating superiority of a specific technique. There are few studies
      reporting on the repair of acute and chronic distal biceps tendon ruptures using
      the EndoButton via an anterior single-incision approach. We report on 27 patients
      who underwent distal biceps tendon repair with an EndoButton. The average age was
      50.1 years (range, 36-78). There were 17 acute repairs (within 4 weeks of
      injury), nine chronic repairs (greater than 4 weeks), and one revision of a
      previous acute repair. All chronic repairs were repaired without the need for
      graft augmentation. Patients were assessed postoperatively using the ASES elbow
      outcome instrument and isokinetic flexion and supination strength and endurance
      testing. Eight control subjects were also tested for comparison. At an average
      follow-up of 30.9 months, 26 of 27 patients returned to their previous employment
      and activity level. The average ASES elbow score was 98.2 (range, 81-100).
      Compared with the contralateral extremity, there was no loss of motion. Average
      flexion strength recovery was 101% and mean supination strength recovery was 99%.
      There was no significant difference in function or strength with repair of acute
      versus chronic ruptures. Using the EndoButton technique, acute and chronic distal
      biceps tendon ruptures can be repaired safely with excellent clinical results.

PMID- 22379437
TI  - Is it true that injecting palmar finger skin hurts more than dorsal skin? New
      level 1 evidence.
AB  - BACKGROUND: Since the first texts on local anesthesia were written in the early
      1900s, it has been widely quoted and believed that dorsal finger skin is less
      sensitive to needlestick pain than volar finger skin. The result is that the most
      commonly used finger block for local anesthesia is the dorsal two injection
      technique. METHODS: In this study, the needlestick discomfort associated with
      dorsal and volar finger skin was compared in a group of 78 volunteers who had the
      long finger of both hands poked with a 25 G needle; one in the midline of the
      volar side and the other in the lateral web space of the dorsal side. Volunteers
      then completed a pain scale for each needlestick and ranked which technique they
      would prefer for future injections. RESULTS: We found that there was no
      significant difference in needlestick pain or preference of future needle
      location between the dorsal and volar aspects of the finger. CONCLUSIONS: We
      provide level 1 evidence that the needlestick of the SIMPLE block which has one
      needlestick on the volar side of the finger is not more painful than the
      needlestick of the dorsal finger block.

PMID- 22379438
TI  - Predictors of successful outcomes in first web space contracture release.
AB  - BACKGROUND: The success of a first web space contracture release is dependent on
      the individual parameters of thumb movement. Examining these parameters
      individually, it is possible to predict which components are important for
      providing successful outcomes. METHODS: We identified all patients who underwent
      a first web space contracture release over 7 years. Patients were examined for
      the following: radial abduction-abduction of the thumb in the plane of the hand;
      palmar abduction-abduction of the thumb 90 degrees  to the plane of the hand; and
      opposition-distance between first and fifth palmar digital crease. Measurements
      were compared between affected and unaffected hands, and correlations between
      components and patients' Disability of the Arm, Shoulder, and Hand (DASH) scores
      were determined. RESULTS: Thirty-nine patients underwent release of a first web
      space contracture; 11 agreed to participate. Opposition distance was
      significantly greater in the affected hand than in the unaffected hand. Grip
      strength was significantly lower in the affected hand. There were no significant
      differences in the radial or palmer abduction angles between hands. There was a
      moderate relationship between opposition distance and DASH score. There was no
      relationship between DASH and the other physical measurements. CONCLUSIONS: It is
      possible to obtain normal radial and palmar abduction angles after first web
      space release; however, success is not dependent on these absolute angles of
      abduction. Success of a release is related to the amount of opposition obtained,
      and it is difficult to achieve equivalent opposition to the unaffected hand. Grip
      strength and opposition remain decreased following contracture release.

PMID- 22379439
TI  - Distal interphalangeal joint arthrodesis with the Herbert headless compression
      screw: outcomes and complications in 64 consecutively treated joints.
AB  - BACKGROUND: Arthrodesis of the distal interphalangeal (DIP) joint is indicated
      for the treatment of arthritis. While several techniques have been recommended,
      the use of headless compression screws has grown in popularity. Rates of union
      reported vary widely, ranging from 80% to 100%, with most studies based on small
      series. The purpose of this study was to review the outcomes and complications
      associated with DIP joint arthrodesis using the Herbert headless compression
      screw in a large case series. METHODS: The medical charts, surgical reports, and
      X-rays for patients undergoing DIP joint arthrodesis with a Herbert screw between
      January 1996 and May 2006 were retrospectively reviewed to determine the
      frequency and types of complications. All operations were performed by the senior
      author at a single institution. RESULTS: Of 64 joints in 51 patients that were
      treated with the Herbert screw, a total of 95% (n = 61) went on to union. Union
      within 3 months occurred in 89% (n = 57) while delayed union (between 3 and 6
      months) occurred in 6% (n = 4). Nonunion requiring subsequent revision
      arthrodesis occurred in 5% (n = 3). Screw removal for symptomatic hardware was
      required in 8% (n = 5). CONCLUSIONS: Fusion of the DIP joint with the Herbert
      screw can be achieved at rates that are comparable to other techniques and other
      headless compressive screws. However, while complications do occur, the Herbert
      screw provides an acceptable rate of union and ease of operative technique,
      making it a suitable procedure for DIP joint arthrodesis.

PMID- 22379440
TI  - Is main operating room sterility really necessary in carpal tunnel surgery? A
      multicenter prospective study of minor procedure room field sterility surgery.
AB  - BACKGROUND: Over 70% of Canadian carpal tunnel syndrome (CTS) operations are
      performed outside of the main operating room (OR) with field sterility and
      surgeon-administered pure local anesthesia [LeBlanc et al., Hand 2(4):173-8, 14].
      Is main OR sterility necessary to avoid infection for this operation? This study
      evaluates the infection rate in carpal tunnel release (CTR) using minor procedure
      room field sterility. METHODS: This is a multicenter prospective study reporting
      the rate of infection in CTR performed in minor procedure room setting using
      field sterility. Field sterility means prepping of the hand with iodine or
      chlorhexidine, equivalent of a single drape, and a sterile tray with modest
      instruments. Sterile gloves and masks are used, but surgeons are not gowned. No
      prophylactic antibiotics are given. RESULTS: One thousand five hundred four
      consecutive CTS cases were collected from January 2008 to January 2010. Six
      superficial infections were reported and four of those patients received oral
      antibiotics. No deep postoperative wound infection was encountered, and no
      patient required admission to hospital, incision and drainage, or intravenous
      antibiotics. CONCLUSIONS: A superficial infection rate of 0.4% and a deep
      infection rate of 0% following CTR using field sterility confirm the low
      incidence of postoperative wound infection using field sterility. This supports
      the safety and low incidence of postoperative wound infection in CTR using minor
      procedure field sterility without prophylactic antibiotics. The higher monetary
      and environmental costs of main OR sterility are not justified on the basis of
      infection for CTR cases.

PMID- 22379441
TI  - The preventive effects of apolipoprotein mimetic D-4F from vibration injury
      experiment in rats.
AB  - Hand-arm vibration syndrome (HAVS) is a debilitating sequela of neurological and
      vascular injuries caused by prolonged occupational exposure to hand-transmitted
      vibration. Our previous study demonstrated that short-term exposure to vibration
      can induce vasoconstriction and endothelial cell damage in the ventral artery of
      the rat's tail. The present study investigated whether pretreatment with D-4F, an
      apolipoprotein A-1 mimetic with known anti-oxidant and vasodilatory properties,
      prevents vibration-induced vasoconstriction, endothelial cell injury, and protein
      nitration. Rats were injected intraperitoneally with 3 mg/kg D-4F at 1 h before
      vibration of the tails for 4 h/day at 60 Hz, 49 m/s(2) r.m.s. acceleration for
      either 1 or 3 days. Vibration-induced endothelial cell damage was examined by
      light microscopy and nitrotyrosine immunoreactivity (a marker for free radical
      production). One and 3-day vibration produced vasoconstriction and increased
      nitrotyrosine. Preemptive treatment with D-4F prevented these negative changes.
      These findings suggest that D-4F may be useful in the prevention of HAVS.

PMID- 22379442
TI  - Posterolateral instability of the elbow in an adolescent boy with a lateral
      epicondyle fracture: a case report.
AB  - BACKGROUND: Posterolateral rotatory instability of elbow is considered to be due
      to the disruption of the ulnar part of the lateral collateral ligament (LUCL).
      This instability pattern may also be induced by a fracture of components of the
      lateral column. RESULTS: We present the case of a 16-year-old boy who fell on his
      left outstretched arm as he attempted to jump over a tennis net. On initial
      physical examination, the elbow had instability found on varus stress and the
      radial head could be felt posteriorly. With attempted valgus and supination force
      combined with axial loading, the elbow gapped open and the patient had a sense of
      increased instability. X-rays showed a fracture of the lateral humeral epicondyle
      and posterolateral subluxation of the elbow. In the operating room, the patient
      was found to have reproducible posterolateral instability of the elbow. The
      lateral epicondyle was found to be fractured off the humerus with the LUCL still
      attached to the fragment. The elbow was reduced, and the injury was stabilized
      with small screws and suture anchors. At 6-month follow-up, the patient was pain
      free, and physical examination revealed 170 degrees  of flexion, full extension,
      90 degrees  of pronation, and 65 degrees  of supination. X-rays showed healing of
      the fracture with concentric reduction of the elbow joint. CONCLUSION: In lateral
      epicondyle fractures, the affected elbow should be assessed for any signs of
      associated instability. If signs of clear instability are seen that would
      prohibit proper postinjury rehabilitation, then surgical reduction and fixation
      of the epicondyle with reinforcement of the LUCL is an effective method of
      treatment.

PMID- 22379443
TI  - Carpal tunnel syndrome due to fibrolipomatous hamartoma of the median nerve.
AB  - Nervous lipofibromatous hamartoma is a rare tumor-like condition involving the
      peripheral nerves, whereby the epineurium and perineurium are enlarged and
      distorted by excess of fatty and fibrous tissues that infiltrate between and
      around nerve boundaries. The median nerve is much more likely to develop a
      hamartoma than other nerves with a predilection for the carpal tunnel. We present
      a case of carpal tunnel syndrome in an adult caused by fibrolipomatous hamartoma
      of the median nerve, successfully removed by excision of the fibrolipomatous
      tissue and decompression.

PMID- 22379444
TI  - Melorheostosis of the thumb and trapezium bone.
AB  - Melorheostosis of the hand is rare. We report a 28-year-old woman with persistent
      pain associated with a slowly growing mass on the dorsum of the right thumb. The
      radiographs, computed tomography, and magnetic resonance imaging were used to
      examine characteristic of melorheostosis involving the trapezium bone, first
      metacarpal, and proximal phalange. The lesions underwent a surgical debulking of
      the hyperostotic cortex and a cortical fenestration.

PMID- 22379445
TI  - Gorham-Stout disease affecting both hands: stabilisation during biphosphonate
      treatment.
AB  - The Gorham-Stout syndrome is a rare condition in which spontaneous, progressive
      resorption of bone occurs. The aetiology is poorly understood. We report a
      patient with osteolysis of the metacarpal bones in both hands due to an increased
      number of stimulated osteoclasts. This suggests that early potent antiresorptive
      therapy with bisphosphonates may prevent local progressive osteolysis.

PMID- 22379446
TI  - Traumatic closed index extensor tendon rupture at the musclotendinous junction: a
      report of two cases.
AB  - This report describes two cases of traumatic closed index extensor tendon rupture
      at the musclotendinous junction. Both patients were injured when their work
      gloves were caught in the revolving parts of machines, and both were treated
      surgically. One of the patients completely ruptured the index extensor digitorum
      communis (EDC) and the extensor indicis proprius (EIP) tendons at the
      musclotendinous junction of dorsal forearm. In this patient, the distal stump of
      the index EDC tendon was sutured to the middle EDC tendon in an end-to-side
      juncture. The other patient completely ruptured the EIP tendon and partially
      ruptured the index EDC tendon at the musclotendinous junction. In this patient,
      tendon transfer of the extensor digiti minimi (EDM) to the EIP tendon and
      plication of the index EDC tendon were performed. In both cases, surgical
      intervention enabled the patients to extend their index fingers almost normally;
      however, the former complained of inability to extend his index finger
      independently. Tendon transfer of the EDM in cases of index extensor tendon
      rupture at the musclotendinous junction is a good method to restore ability to
      independently extend the index finger. However, consideration should be given to
      anatomical variation in the little finger. The EDC tendon is sometimes absent
      leaving the EDM tendon as the only extensor tendon to the little finger.

PMID- 22379447
TI  - Prosthetic hemi-arthroplasty for post-traumatic articular cartilage loss in the
      proximal interphalangeal joint.
AB  - This article discusses the indications, contra-indications, and technique for
      proximal interphalangeal joint prosthetic hemi-arthroplasty in the setting of sub
      acute or chronic post-traumatic articular cartilage loss. Two case examples are
      provided: one for replacement of the head of the proximal phalanx, the other for
      replacement of the base of the middle phalanx.This procedure serves as a recently
      available alternative to fusion, silicone total joint replacement, total joint
      arthroplasty with unlinked surface replacements, volar plate arthroplasty, hemi
      condylar osteochondral autograft reconstruction, or free vascularized joint
      transfer.

PMID- 22379448
TI  - Vascularized genicular osseous-periosteal flap for pseudarthrosis of the proximal
      phalanx of the little finger: a case report.
AB  - This study describes pseudoarthrosis of the proximal phalanx of the little finger
      and its successful treatment using a free vascularized genicular osseous
      periosteal flap. Since this thin and pliable flap can be harvested as a small
      vascularized unit, it is ideal for the treatment of phalangeal pseudoarthrosis.

PMID- 22379449
TI  - Complications of suture ligation ablation for ulnar polydactyly: a report of two
      cases.
AB  - We report two cases resulting in complications following suture ligation
      treatment for ulnar polydactyly. One case consisted of bilateral, retained
      gangrene and cellulitis, and a second case consisted of a residual, sensitive
      skin tag. The case involving gangrene and cellulitis developed after an
      unsuccessful suture ligation of bilateral pedunculated duplicated digits. The
      second case developed after suture ligature ablation of a rudimentary digit in
      the nursery but presented 3 years later with a residual symptomatic nubbin. Both
      cases were treated by surgical excision of the residual tissue in the operating
      room. The first case illustrates a morbid complication following unsuccessful
      ligature while the second case demonstrates the inevitable suboptimal long-term
      outcome associated with what has traditionally been considered "successful"
      suture ligation.

PMID- 22379450
TI  - Bilateral scaphotrapezium coalition with bilateral scaphoid nonunion in a patient
      with Klippel-Feil syndrome: a case report.

PMID- 22379451
TI  - Compartment syndrome in all four extremities: a rare case associated with
      systemic capillary leak syndrome.
AB  - While isolated limb injuries often lead to suspicion for and treatment of
      compartment syndrome, multi-limb compartment syndrome induced by a systemic
      disease is a rare entity, in which lack of immediate diagnosis can have
      catastrophic consequences to the patient. We present a patient with idiopathic
      systemic capillary leak syndrome (SCLS) resulting in compartment syndrome in all
      four extremities. Treatment required bilateral hand, forearm, calf, and thigh
      fasciotomies. Presenting symptoms included pain in all four extremities, malaise,
      and confusion. Laboratory data included polycythemia, hypoalbuminemia,
      leukocytosis, and elevated creatinine, but not a monoclonal spike on serum
      electrophoresis as is common in SCLS. Thus, when faced with clinical evidence of
      multiple extremity compartment syndrome, the surgeon should consider systemic
      disorders, such as SCLS, and aggressively treat the compartment syndrome as well
      as the underlying disease.

PMID- 22379452
TI  - Etiology and treatment of pediatric trigger finger: possible application of
      partial V-shaped resection of the central part of flexor digitorum superficialis
      through our case presentation.

PMID- 22379453
TI  - Autoimmune neurologic disorders.

PMID- 22379454
TI  - Autoimmune neuromuscular disorders.
AB  - Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular
      junction or muscle have a wide clinical spectrum with diverse pathogenetic
      mechanisms. Peripheral nervous system may be targeted in the context of complex
      immune reactions involving different cytokines, antigen-presenting cells, B cells
      and different types of T cells. Various immunomodulating and cytotoxic treatments
      block proliferation or activation of immune cells by different mechanisms
      attempting to control the response of the immune system and limit target organ
      injury. Most treatment protocols for autoimmune neuromuscular disorders are based
      on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis,
      with cytotoxic agents mostly used as steroid-sparing medications. More recently,
      development of specific monoclonal antibodies targeting individual cell types
      allowed a different approach targeting specific immune pathways, but these new
      treatments are also associated with various adverse effects and their long-term
      efficacy is still unknown.

PMID- 22379455
TI  - Multiple sclerosis: pathogenesis and treatment.
AB  - Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating
      disease of the central nervous system. It affects approximately 400,000 people in
      the United States and onset is usually during young adulthood. There are four
      clinical forms of MS, of which relapsing remitting type is the most common. As
      the etiology of MS is unknown, finding a cure will remain challenging. The main
      mechanism of injury appears to be inflammation and 8 agents are now FDA approved
      to help control MS. These agents for relapsing forms of MS target different parts
      of the immune system, with the end goal of decreasing and avoiding further
      inflammation. No agents are FDA approved for the primary progressive version of
      MS. FDA approved agents include four preparations of interferon beta (Avonex,
      Rebif, Betaseron and Extavia), glatiramer acetate (Copaxone), mitoxantrone
      (Novantrone), natalizumab (Tysabri) and fingolimod (Gilenya). There are several
      drug undergoing phase II and III trials. The heterogeneity of the MS disease
      process, individual patient response, and medication toxicities continue to
      challenge the treating physician.

PMID- 22379457
TI  - Neurosarcoidosis.
AB  - Neurosarcoidosis is an uncommon but potentially serious manifestation of
      sarcoidosis. While the cranial nerves are most frequently affected,
      neurosarcoidosis can involve other nervous system tissues including the meninges,
      brain parenchyma (especially the hypothalamic region), spinal cord, peripheral
      nerve, and muscle. Diagnosis may be particularly challenging when
      neurosarcoidosis occurs in isolation. Diagnostic criteria usually include
      histologic identification of a noncaseating granuloma, supportive laboratory or
      imaging tests or both, and a compatible clinical course. Treatment has not been
      subjected to rigorous study, but corticosteroids are typically the first line of
      therapy and approximately half of patients have substantial benefit. For patients
      who are refractory to or intolerant of corticosteroid therapy, second-line agents
      include azathioprine, methotrexate, cyclosporine, cyclophosphamide,
      mycophenolate, and even cranial irradiation. The combination of infliximab and
      mycophenolate mofetil is under study as well. Treatment options will likely
      evolve as well-designed studies are undertaken.

PMID- 22379456
TI  - Idiopathic transverse myelitis and neuromyelitis optica: clinical profiles,
      pathophysiology and therapeutic choices.
AB  - Transverse myelitis is a focal inflammatory disorder of the spinal cord which may
      arise due to different etiologies. Transverse myelitis may be idiopathic or
      related/secondary to other diseases including infections, connective tissue
      disorders and other autoimmune diseases. It may be also associated with optic
      neuritis (neuromyelitis optica), which may precede transverse myelitis. In this
      manuscript we review the pathophysiology of different types of transverse
      myelitis and neuromyelitis optica and discuss diagnostic criteria for idiopathic
      transverse myelitis and risk of development of multiple sclerosis after an
      episode of transverse myelitis. We also discuss treatment options including
      corticosteroids, immunosuppressives and monoclonal antibodies, plasma exchange
      and intravenous immunoglobulins.

PMID- 22379458
TI  - Central nervous system vasculitis: still more questions than answers.
AB  - The central nervous system (CNS) may be involved by a variety of inflammatory
      diseases of blood vessels. These include primary angiitis of the central nervous
      system (PACNS), a rare disorder specifically targeting the CNS vasculature, and
      the systemic vasculitides which may affect the CNS among other organs and
      systems. Both situations are severe and convey a guarded prognosis. PACNS usually
      presents with headache and cognitive impairment. Focal symptoms are infrequent at
      disease onset but are common in more advanced stages. The diagnosis of PACNS is
      difficult because, although magnetic resonance imaging is almost invariably
      abnormal, findings are non specific. Angiography has limited sensitivity and
      specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis
      when disclosing blood vessel inflammation and are also useful to exclude other
      conditions presenting with similar findings. However, since lesions are
      segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS
      involvement by systemic vasculitis occurs in less than one fifth of patients but
      may be devastating. A prompt recognition and aggressive treatment is crucial to
      avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are
      recommended for patients with PACNS and for patients with secondary CNS
      involvement by small-medium-sized systemic vasculitis. CNS involvement in large
      vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell
      arteritis) or glucocorticoids and immunosuppressive agents (Takayasu's disease).
      However, in large vessel vasculitis, where CNS symptoms are usually due to
      involvement of extracranial arteries (Takayasu's disease) or proximal portions of
      intracranial arteries (giant-cell arteritis), revascularization procedures may
      also have an important role.

PMID- 22379459
TI  - Neuropsychiatric systemic lupus erythematosus.
AB  - Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood,
      yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE
      is multifactorial and involves various inflammatory cytokines, autoantibodies,
      and immune complexes resulting in vasculopathic, cytotoxic and autoantibody
      mediated neuronal injury. The management of NPSLE is multimodal and has not been
      subjected to rigorous study. Different treatment regimens include nonsteroidal
      anti-inflammatory drugs, anticoagulation, and immunosuppressives such as
      cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For
      refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and
      rituximab have been used. Adjunctive symptomatic treatment complements these
      therapies by targeting mood disorders, psychosis, cognitive impairment, seizures
      or headaches. Several new biological agents are being tested including Belimumab,
      a human monoclonal antibody that targets B lymphocyte stimulator. This review
      focuses on the pathophysiology, treatment, and new potential therapies for
      neuropsychiatric manifestations of systemic lupus erythematosus.

PMID- 22379460
TI  - Autoimmune channelopathies of the nervous system.
AB  - Ion channels are complex transmembrane proteins that orchestrate the electrical
      signals necessary for normal function of excitable tissues, including the central
      nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress
      in molecular biology has allowed cloning and expression of genes that encode
      channel proteins, while comparable advances in biophysics, including patch-clamp
      electrophysiology and related techniques, have made the functional assessment of
      expressed proteins at the level of single channel molecules possible. The role of
      ion channel defects in the pathogenesis of numerous disorders has become
      increasingly apparent over the last two decades. Neurological channelopathies are
      frequently genetically determined but may also be acquired through autoimmune
      mechanisms. All of these autoimmune conditions can arise as paraneoplastic
      syndromes or independent from malignancies. The pathogenicity of autoantibodies
      to ion channels has been demonstrated in most of these conditions, and patients
      may respond well to immunotherapies that reduce the levels of the pathogenic
      autoantibodies. Autoimmune channelopathies may have a good prognosis, especially
      if diagnosed and treated early, and if they are non-paraneoplastic. This review
      focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion
      channel disorders of the nervous system.

PMID- 22379461
TI  - Toxicities of immunosuppressive treatment of autoimmune neurologic diseases.
AB  - In parallel to our better understanding of the role of the immune system in
      neurologic diseases, there has been an increased availability in therapeutic
      options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia
      gravis, polyneuropathies, central nervous system vasculitides and
      neurosarcoidosis. In many cases, the purported benefits of this class of therapy
      are anecdotal and not the result of good controlled clinical trials. Nonetheless,
      their potential efficacy is better known than their adverse event profile. A
      rationale therapeutic decision by the clinician will depend on a comprehensive
      understanding of the ratio between efficacy and toxicity. In this review, we
      outline the most commonly used immune suppressive medications in neurologic
      disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors,
      monoclonal antibodies and miscellaneous immune suppressants. A discussion of
      their mechanisms of action and related toxicity is highlighted, with the goal
      that the reader will be able to recognize the most commonly associated toxicities
      and identify strategies to prevent and manage problems that are expected to arise
      with their use.

PMID- 22379464
TI  - Intrahepatic cholangiocarcinoma with sarcomatous changes.
AB  - A 61-year-old Japanese male was seen at an outside hospital with abdominal pain
      and distention. An intraabdominal mass was found on abdominal computed tomography
      (CT), and he was referred for further evaluation. He was afebrile, with mild
      tenderness in the upper abdomen and massive distention. Routine blood work showed
      severe inflammation and anemia. Repeat CT showed a large solitary heterogeneous
      mass, 25 cm in diameter, in the left upper quadrant with evidence of intratumoral
      bleeding and irregular enhancement peripherally. There was no clear distinction
      between the mass and the peripheral organs. Surgery was performed with persistent
      anemia and exacerbation of abdominal pain. Lateral segmentectomy, total
      gastrectomy, cholecystectomy and partial resection of the diaphragm and parietal
      peritoneum were performed. The final diagnosis was cholangiocarcinoma with
      sarcomatous changes. On the 16th postoperative day a CT scan revealed recurrent
      tumor. The patient died on the 34th postoperative day from rapid tumor
      progression.

PMID- 22379463
TI  - Raphe-Hippocampal Serotonin Neurotransmission In The Sex Related Differences of
      Adaptation to Stress: Focus on Serotonin-1A Receptor.
AB  - Stress is the major predisposing and precipitating factor in the onset of
      depression which is the most significant mental health risk for women. Behavioral
      studies in animal models show that female sex though less affected by an acute
      stressor; exposure to repeated stressors induces coping deficits to impair
      adaptation in them. A decrease in the function of 5-hydroxytryptamine (5-HT;
      serotonin) in the hippocampus and an increased function of the 5-HT-1A receptor
      in the raphe nucleus coexist in depression. Pharmacological and neurochemical
      data are relevant that facilitation of serotonin neurotransmission via
      hippocampus due to desensitization of somatodendritic 5-HT1A receptors may lead
      to adaptation to stress. The present article reviews research on sex related
      differences of raphe-hippocampal serotonin neurotransmission to find a possible
      answer that may account for the sex differences of adaptation to stress reported
      in preclinical research and greater incidence of depression in women than men.

PMID- 22379466
TI  - Intussusception of the small intestine caused by a primary melanoma?
AB  - Although the gastrointestinal tract is a fairly frequent site of melanoma
      metastases, reports of small bowel intussusception caused by melanoma are very
      rare. We report the case of a 77-year-old man who was admitted to our hospital
      with epigastric pain, melena and anaemia. After clinical examination, laboratory
      evaluation and radiological work-up the diagnosis of a jejunal intussusception
      was made. Exploratory laparoscopy revealed a large tumour arising from the
      jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection
      with an end-to-end anastomosis was performed. Histological examination showed an
      intestinal melanoma. There are different theories concerning the origin of
      malignant melanoma in the small bowel. Although the small and large intestines
      normally contain no melanocytes, these cells have occasionally been found in the
      alimentary and respiratory tracts and even in lymph nodes, which supports the
      theory of a primary origin of melanoma at these sites. Since this was a solitary
      intestinal lesion and there was no history of cutaneous melanoma, we conclude
      that this could be an example of a very rare primary melanoma of the small
      intestine.

PMID- 22379465
TI  - Intramural duodenal haematoma after endoscopic biopsy: case report and review of
      the literature.
AB  - The development of intramural duodenal haematoma (IDH) after small bowel biopsy
      is an unusual lesion and has only been reported in 18 children. Coagulopathy,
      thrombocytopenia and some special features of duodenal anatomy, e.g. relatively
      fixed position in the retroperitoneum and numerous submucosal blood vessels, have
      been suggested as a cause for IDH. The typical clinical presentation of IDH is
      severe abdominal pain and vomiting due to duodenal obstruction. In addition, it
      is often associated with pancreatitis and cholestasis. Diagnosis is confirmed
      using imaging techniques such as ultrasound, magnetic resonance imaging or
      computed tomography and upper intestinal series. Once diagnosis is confirmed and
      intestinal perforation excluded, conservative treatment with nasogastric tube and
      parenteral nutrition is sufficient. We present a case of massive IDH following
      endoscopic grasp forceps biopsy in a 5-year-old girl without bleeding disorder or
      other risk for IDH, which caused duodenal obstruction and mild pancreatitis and
      resolved within 2 weeks of conservative management. Since duodenal biopsies have
      become the common way to evaluate children or adults for suspected enteropathy,
      the occurrence of this complication is likely to increase. In conclusion, the
      review of the literature points out the risk for IDH especially in children with
      a history of bone marrow transplantation or leukaemia.

PMID- 22379467
TI  - Untreated celiac disease in a patient with dermatitis herpetiformis leading to a
      small bowel carcinoma.
AB  - Usually, celiac disease has a benign course, though the overall morbidity and
      mortality have increased. Treatment with a gluten-free diet restores the damaged
      intestinal mucosa. In rare cases a small bowel adenocarcinoma develops.
      Unfortunately, the clinical presentation is not always recognized and prognosis
      is bad. We present a 69-year-old man with a history of dermatitis herpetiformis
      who presented to our tertiary center for a second opinion for a suspected gastric
      motility disorder. This diagnosis was based on the combination of upper abdominal
      pain for over 2 years and repetitive episodes of vomiting. Immediately after
      referral, celiac disease was diagnosed and a gluten-free diet was started. In the
      next half year of follow-up, additional anemia and weight loss developed and
      eventually a small bowel adenocarcinoma was diagnosed. Revision of a small bowel
      follow-through, which had been performed 2 years earlier, showed that the tube
      had been positioned just distal from the process. Therefore, this diagnosis had
      not been made at that time. Unfortunately, curative therapy was not possible and
      the patient died a few months later. In conclusion, all patients with dermatitis
      herpetiformis have a gluten-sensitive enteropathy and should be treated with a
      gluten-free diet. Next to this it is important to notice that patients with
      celiac disease have an increased risk of developing a small bowel malignancy.
      Unexplained upper abdominal pain, weight loss and anemia should lead to
      additional investigations to exclude a small bowel malignancy in these patients.
      At last, the diagnosis of a small bowel carcinoma is difficult. Together with the
      radiologist, the optimal techniques for visualization of this malignancy should
      be considered.

PMID- 22379468
TI  - Tricholithobezoar causing gastric perforation.
AB  - A bezoar is an intraluminal mass formed by the accumulation of undigested
      material in the gastrointestinal tract. Trichobezoar is a rare condition seen
      almost exclusively in young women with trichotillomania and trichotillophagia.
      When not recognized, the trichobezoar continues to grow, which increases the risk
      of severe complications such as gastric ulceration and even perforation.
      Formation of a gallstone within the trichobezoar (tricholithobezoar) is an event
      that has not yet been described. We report the case of a 22-year-old woman
      admitted to the emergency room with signals and symptoms of an epigastric mass
      and perforative acute abdomen. Radiological study revealed bilateral
      pneumoperitoneum. Personal history revealed depressive syndrome, trichotillomania
      and trichophagia. With a diagnosis of visceral perforation, an urgent exploratory
      laparotomy was performed. This confirmed the diagnosis of gastric perforation due
      to a large trichobezoar with the formation of a gastrolith that was removed by
      anterior gastrotomy. Biochemical study of the gastric stone revealed that it was
      composed of bile salts. There were no complications. The patient was discharged
      on the 5th postoperative day and was referred for psychiatric treatment.

PMID- 22379469
TI  - Spindle and giant cell type undifferentiated carcinoma of the proximal bile duct.
AB  - Undifferentiated spindle and giant cell carcinoma is an extremely rare malignant
      neoplasm arising in the extrahepatic bile duct. We herein present the case of a
      67-year-old male who developed an undifferentiated spindle and giant cell
      carcinoma of the proximal bile duct. A nodular infiltrating tumor was located at
      the proximal bile duct, resulting in obstructive jaundice. Histologically, the
      tumor was composed of mainly spindle-shaped and giant cells and showed positive
      immunoreactivity for both cytokeratin and vimentin. Adjuvant chemotherapy was
      administered following extrahepatic bile duct resection, and he has been doing
      well for 16 months since the surgical treatment. The literature on this rare
      malignancy is also reviewed and discussed.

PMID- 22379462
TI  - Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications
      for Sex Differences, Early Stress and Prenatal SSRI Exposure.
AB  - Prenatal cocaine (PC) exposure negatively impacts the developing nervous system,
      including numerous changes in serotonergic signaling. Cocaine, a competitive
      antagonist of the serotonin transporter, similar to selective serotonin reuptake
      inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving
      the direct mechanism through which cocaine disrupts the developing serotonin
      system unclear. In order to understand the role of the serotonin transporter in
      cocaine's effect on the serotonergic system, we compare reports concerning PC and
      prenatal antidepressant exposure and conclude that PC exposure affects many
      facets of serotonergic signaling (serotonin levels, receptors, transporters) and
      that these effects differ significantly from what is observed following prenatal
      SSRI exposure. Alterations in serotonergic signaling are dependent on timing of
      exposure, test regimens, and sex. Following PC exposure, behavioral disturbances
      are observed in attention, emotional behavior and stress response, aggression,
      social behavior, communication, and like changes in serotonergic signaling, these
      effects depend on sex, age and developmental exposure. Vulnerability to the
      effects of PC exposure can be mediated by several factors, including allelic
      variance in serotonergic signaling genes, being male (although fewer studies have
      investigated female offspring), and experiencing the adverse early environments
      that are commonly coincident with maternal drug use. Early environmental stress
      results in disruptions in serotonergic signaling analogous to those observed with
      PC exposure and these may interact to produce greater behavioral effects observed
      in children of drug-abusing mothers. We conclude that based on past evidence,
      future studies should put a greater emphasis on including females and monitoring
      environmental factors when studying the impact of PC exposure.

PMID- 22379470
TI  - Cinacalcet for hypercalcemia caused by pulmonary squamous cell carcinoma
      producing parathyroid hormone-related Peptide.
AB  - BACKGROUND: Current treatments for hypercalcemia caused by lung cell carcinomas
      producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy,
      probably because of their lack of effect on PTH-rp secretion. In this case study
      we explored the efficacy of the calcimimetic cinacalcet as suppressor of PTH-rp
      production. PATIENT: A 57-year-old male with severe and recurrent hypercalcemia
      induced by a PTH-rp-producing squamous cell lung carcinoma, stage cT4N3M1b,
      poorly responding to standard treatments. RESULTS: Serum PTH-rp levels were not
      affected by saline, calcitonin or zoledronate. PTH-rp decreased during
      chemotherapy and cinacalcet monotherapy. The combination of chemotherapy plus
      cinacalcet was most effective in rapidly reducing serum calcium and PTH-rp.
      CONCLUSION: This case study is the first to suggest that cinacalcet may be of
      value in some cases of PTH-rp-dependent hypercalcemia. Corroborative evidence is
      needed.

PMID- 22379471
TI  - Occult breast cancer presenting as metastatic adenocarcinoma of unknown primary:
      clinical presentation, immunohistochemistry, and molecular analysis.
AB  - We report a rare presentation of a 66-year-old female with diffuse metastatic
      adenocarcinoma of unknown primary involving liver, lymphatic system and bone
      metastases. The neoplastic cells were positive for CK7 and OC125, while negative
      for CK20, thyroid transcription factor 1, CDX2, BRST-2, chromogranin,
      synaptophysin, estrogen receptor (ER), progesterone receptor (PR), and human
      epidermal growth factor receptor 2 (HER2/neu). Fluorescence in situ hybridization
      showed no amplification of the HER2/neu gene. Molecular profiling reported a
      breast cancer origin with a very high confidence score of 98%. The absence of
      immunohistochemistry staining for ER, PR, and HER2/neu further classified her
      cancer as triple-negative breast cancer. Additional studies revealed high
      expression levels of topoisomerase (Topo) I, androgen receptor, and
      ribonucleoside-diphosphate reductase large subunit; the results were negative for
      thymidylate synthase, Topo II-a and O6-methylguanine-DNA methyltransferase. The
      patient was initially treated with a combination regimen of cisplatin and
      etoposide, and she experienced a rapid resolution of cancer-related symptoms.
      Unfortunately, her therapy was complicated by a cerebrovascular accident (CVA),
      which was thought to be related to cisplatin and high serum mucin. After recovery
      from the CVA, the patient was successfully treated with second-line chemotherapy
      based on her tumor expression profile. We highlight the role of molecular
      profiling in the diagnosis and management of this patient and the implication of
      personalized chemotherapy in this challenging disease.

PMID- 22379472
TI  - Colon cancer perforation presenting as a strangulating ventral hernia.
AB  - Colorectal cancer remains the second leading cause of death from malignant
      disease. Despite improvements in the treatment modalities offered to patients,
      more than half of the operated patients die from the disease. The most common
      presenting symptoms of colonic carcinoma are changes in bowel habits, bleeding,
      abdominal pain, abdominal mass, stools mixed with mucus or not, weight loss,
      anorexia, and other characteristics related to metastasis. Here, the case of a 74
      year-old female patient with colon cancer perforation presenting as a
      strangulating ventral hernia and a mini-review of the current literature are
      presented.

PMID- 22379473
TI  - Solitary fibrous tumor of the prostate: case report and review of the literature.
AB  - Solitary fibrous tumor (SFT), usually described in the pleura, is exceedingly
      rare in the prostate. We report a 60-year-old man with prostatic SFT revealed by
      obstructive urinary symptoms, and detected by ultrasonography. Computed
      tomography (CT) and magnetic resonance imaging suggested a prostatic origin. CT
      guided tumor biopsy diagnosed a SFT. A cystoprostatectomy was performed.
      Pathologic examination showed a 15-cm tumor arising from the prostate and showing
      histological criteria suggestive of aggressiveness. The surgical resection
      margins were tumor-free. The patient was then regularly monitored and is still
      alive in complete remission, 28 months after surgery. In conclusion, we report a
      new exceptional case of prostatic SFT. We review the literature and discuss the
      challenging issues of misdiagnosis, prognosis and treatment.

PMID- 22379474
TI  - Metastatic renal cell carcinoma: the importance of immunohistochemistry in
      differential diagnosis.
AB  - INTRODUCTION: Clear cell carcinoma accounts for 75% of all types of renal
      neoplasms. Approximately one third presents with metastatic disease at diagnosis.
      Immunohistochemical studies play a significant diagnostic role. CASE REPORT: We
      report the case of a 48-year-old heavy smoker who presented with productive cough
      and progressive dyspnea. The study revealed a renal mass and lung alterations
      compatible with primary tumor of the lung. The patient underwent a right complete
      nephrectomy. The anatomopathological exam showed clear cell renal carcinoma
      (pT1bN0Mx). After transthoracic needle aspiration biopsy, the clinical diagnosis
      was stage IV adenocarcinoma of the lung. Initially, the patient received one
      cycle of chemotherapy (cisplatin/pemetrexed). Two weeks later, the
      immunohistochemistry tests revealed a secondary lesion with probable renal
      origin. Chemotherapy was stopped and the patient was started on sunitinib
      treatment. After two cycles the disease progressed. A second-line treatment with
      everolimus was proposed; however, the patient died 2 weeks later due to terminal
      respiratory insufficiency. DISCUSSION: Clear cell renal cell carcinoma remains
      one of the great mimickers in pathology. Immunohistochemistry is a valuable tool
      in the differential diagnosis of lung carcinomas. With the help of thyroid
      transcription factor 1, it is possible to distinguish a primary lung tumor from a
      metastasis with a reasonable degree of certainty. The present case report
      illustrates the challenge of making a definitive and adequate diagnosis. The
      immunohistochemistry added information that changed the whole treatment strategy.
      For the best treatment approach, it is fundamental that clinicians await all
      possible test results, before establishing a treatment plan.

PMID- 22379475
TI  - Acute cavernous sinus syndrome from metastasis of lung cancer to sphenoid bone.
AB  - Cavernous sinus syndrome is a rare entity in oncology reported only in occasional
      case reports. Optimal therapy is thus poorly defined with rapidly progressive
      disease dominating the picture. Management includes prompt diagnosis, attempts at
      stabilization of cranial nerve function, and aggressive control of central pain
      syndrome. Here, we report cavernous sinus syndrome secondary to the original
      squamous cell carcinoma of the lung. With common presenting causes of this
      syndrome being infection, thrombosis or tumor, it might seem that metastatic
      tumor would be expected in a patient with a cancer diagnosis. What was not so
      expected was the extremely rapid progression from mild headache and mild
      trigeminal neuralgia with negative-contrast head CT to a massive, destructive
      lesion involving several skull bones and skull base, only 3 weeks later. In
      addition, the patient was severely immunosuppressed at the completion of
      induction chemotherapy. Infectious processes, although unlikely, were considered,
      as aggressive cancer therapy (including high-dose steroids and radiation therapy)
      had no impact on this disease. Despite accurate localization, the aggressive
      nature of this disease with massive bone destruction and dural thickening limited
      any chance of a durable control. We discuss the process of evaluation, diagnosis
      and treatment of symptoms and the importance of a team approach to best palliate
      these unfortunate patients.

PMID- 22379476
TI  - Unusual presentation of a left testicular carcinoid.
AB  - Testicular carcinoid generally presents either with a palpable (painful or
      painless) or rarely a nonpalpable mass (when it is diagnosed incidentally on
      scrotal imaging) of the involved testis. An ipsilateral testicular carcinoid
      presenting exclusively with contralateral testicular symptoms has never been
      described in the literature to date. We report a case of nonpalpable left
      testicular carcinoid diagnosed incidentally on a sonogram done for right
      testicular pain and swelling, with conspicuous absence of left testicular
      symptoms. This case highlights the importance of recognizing such an atypical
      presentation of testicular carcinoid.

PMID- 22379477
TI  - Irinotecan-induced dysarthria.
AB  - Colorectal carcinomas are among the most common tumor types and are generally
      treated with palliative chemotherapy in case of metastatic disease. Here, we
      describe the case of a 46-year-old patient with metastatic rectal carcinoma who
      received second-line therapy with irinotecan and developed isolated transient
      dysarthria (with normal MR imaging of the brain) following each administration of
      irinotecan. Neurological and logopedical evaluation revealed that the dysarthria
      predominantly resulted from a reduced capacity in fine-tuning of motor functions
      of the tip of the tongue and a minimal reduction in the power of speech at
      labiodental contact. As hypoglossal nerve activity has been reported to be
      especially susceptible to cholinergic stimulation and irinotecan can cause
      cholinergic side effects by binding to and inactivating acetylcholinesterase, we
      suspect this mechanism to be responsible for irinotecan-induced dysarthria.

PMID- 22379478
TI  - Therapeutic and diagnostic implication of inadequate circle of willis in a
      patient with acute spontaneous bilateral internal carotid artery dissection: case
      report and review of the literature.
AB  - BACKGROUND AND PURPOSE: Emphasizing the therapeutic and diagnostic implications
      of concomitant inadequate collaterals from the circle of Willis in a rare case of
      spontaneous acute bilateral internal carotid artery dissection (BICAD) following
      5 days of isolated rigorous cough (pertussis like). CASE DESCRIPTION: A 45-year
      old male has been referred to our department with rapid neurological
      deterioration consisting of dysarthria and severe left hemiparesis following 5
      days of isolated rigorous cough. CTA demonstrated BICAD, a tiny anterior
      communicating artery and no bilateral posterior communicating artery. The patient
      had no personal or familial risk factors. Infectious, traumatic, vascular and
      connective tissue diseases were ruled out. RESULTS: Neurological deterioration
      persisted despite immediate provision of continuous 'full-heparinization' with
      concomitant rigorous control of blood pressure. Endovascular treatment consisting
      of bilateral stenting was undertaken. Ten days later, the patient was discharged
      with mild hemiparesis and resuming normal activity after 3 months. CONCLUSIONS:
      BICAD with concomitant inadequate collaterals from the circle of Willis may
      predispose to hypoperfusion which might not respond to the usual conservative
      treatment prompting for flow reestablishment. Moreover, isolated rigorous cough
      can cause acute spontaneous BICAD even among patients without any risk factors.

PMID- 22379479
TI  - Cerebral Embolic Activity in a Patient during Acute Crisis of Takayasu's
      Arteritis.
AB  - Takayasu's arteritis is a disease that affects large vessels and may cause
      neurological symptoms either by stenoses/occlusions or embolisms from vessels
      with an inflammatory process. Transcranial Doppler (TCD) ultrasound can provide
      useful information for diagnosis and monitoring during the active phase of the
      disease. Cerebral embolic signals can be detected by TCD and have been considered
      a risk factor for vascular events. We report a patient in whom TCD ultrasound was
      used to monitor cerebral embolic signals during the active phase of the disease.
      This case report suggests that embolic activity in Takayasu's arteritis may
      represent disease activity, and its monitoring may be useful for evaluating the
      response to therapy.

PMID- 22379480
TI  - IV Thrombolysis-Bridging and Endovascular Treatment for Occlusive Internal
      Carotid Artery Dissection with Tandem Occlusion.
AB  - Compared to other etiologies of ischemic stroke, occlusive internal carotid
      artery dissection responds worse to intravenous (IV) thrombolysis. Intracranial
      tandem occlusion is a predictor of poor outcome. A direct endovascular approach
      has been proposed as a safe and probably superior alternative to IV thrombolysis.
      However, it may lead to considerable treatment delays. We used rapidly initiated
      IV thrombolysis-bridging and subsequent endovascular treatment in two patients
      with severe hemispheric ischemia due to occlusive internal carotid artery
      dissection with tandem occlusion and achieved good outcomes. Minimizing
      recanalization times likely improves patient outcome and IV thrombolysis-bridging
      may be a reasonable strategy to achieve this. The positive initial results
      obtained with endovascular approaches and IV thrombolysis-bridging in this
      patient group deserve further scientific exploration.

PMID- 22379481
TI  - The time of cholera.

PMID- 22379482
TI  - Identification of acute vaccine-preventable hepatitis in individuals with chronic
      hepatitis in British Columbia between 1991 and 2007.
AB  - BACKGROUND: In British Columbia (BC), hepatitis A virus (HAV) and hepatitis B
      virus (HBV) vaccines are provincially funded for persons with chronic hepatitis
      infections. PURPOSE: To assess the effectiveness of BC public health follow-up of
      HBV and hepatitis C virus (HCV) cases and immunization policy by determining the
      number of vaccine-preventable acute hepatitis infections reported following a
      chronic HBV or HCV diagnosis, by examining demographic characteristics and by
      observing temporal trends. METHODS: All newly identified cases of HAV, HBV and
      HCV between 1991 and October 2007 were extracted from the BC integrated Public
      Health Information System and linked to ascertain cases of hepatitis
      suprainfection. RESULTS: Between 1991 and October 2007, 30 BC residents with
      chronic HBV and 104 with HCV were subsequently diagnosed with HAV. Acute HBV was
      identified in 162 persons previously diagnosed with HCV. Significantly more men
      than women developed hepatitis suprainfection (P<0.0001), but women were of a
      younger age when they were diagnosed with HAV (P=0.02) and acute HBV (P=0.0002).
      HAV suprainfection cases among those with HCV peaked in 1998 at 33 cases and
      declined to zero cases in 2007. In comparison, HBV suprainfection among
      individuals with chronic HCV peaked in 1996 at 26 cases and declined to two cases
      in 2007. DISCUSSION: Cases of HAV and acute HBV have declined among HCV-infected
      individuals. However, despite the availability of publicly funded vaccines for
      high-risk groups, a substantial number of acute HBV infections post-HCV
      identification are still identified, indicating that follow-up and vaccination
      coverage should be improved in these populations.

PMID- 22379483
TI  - Heterogeneity of rotavirus testing and admitting practices for gastroenteritis
      among 12 tertiary care pediatric hospitals: Implications for surveillance.
AB  - BACKGROUND: The Canadian Immunization Monitoring Program, ACTive (IMPACT)
      surveillance for rotavirus relies on monitoring hospital admissions. Because a
      diagnosis of rotavirus is not necessary for treatment purposes, and rotavirus is
      not a reportable disease, wide variation may exist in the admitting and testing
      practices for this disease. From 2005 to 2007, the number of rotavirus admissions
      differed significantly among IMPACT centres, and this variation could not be
      explained by population differences alone. Understanding this variation is
      important when interpreting surveillance data and estimating the cost
      effectiveness of rotavirus vaccination programs. METHODS: Key informant
      interviews were conducted with pediatric infectious disease physicians and IMPACT
      nurse monitors involved with rotavirus surveillance to obtain in-depth
      information about rotavirus testing and admitting practices at each of the 12
      IMPACT centres. RESULTS: A total of 18 of 24 interviews were completed, with at
      least one interview conducted with physicians and/or nurses at each centre. Four
      major differences were identified among the centres: case-identification methods,
      admission definitions, admission criteria and testing criteria. The criteria for
      admitting and testing patients as well as which patients were defined as
      admissions had the greatest influence on case totals. DISCUSSION: The present
      study found that differences in admitting and testing practices may contribute to
      significant differences in rotavirus admission totals. Given these differences,
      caution should be used when using local case estimates for cost-effectiveness
      analyses and immunization program decisions. The present study illustrates that
      understanding the factors that influence the identification of a disease is
      important when interpreting and applying surveillance data.

PMID- 22379484
TI  - Evaluation of the Do Bugs Need Drugs? program in British Columbia: Can we curb
      antibiotic prescribing?
AB  - OBJECTIVE: Antibiotic resistance is accelerated by the overuse of antibiotics. Do
      Bugs Need Drugs? is an educational program adapted in British Columbia to target
      both the public and health care professionals, with the aim of reducing
      unnecessary prescribing. The current article presents a descriptive evaluation of
      the impact of the program over the first four years. METHOD: Program
      implementation was measured by the amount of educational material distributed and
      the level of participation in educational sessions. The impact of the program was
      assessed by measuring changes in knowledge and prescribing habits of
      participating physicians, and by investigating provincial trends in antibiotic
      use. RESULTS: A total of 51,367 children, assisted-living residents and health
      care professionals have participated in the program since its inception in the
      fall of 2005. Pre- and postcourse assessments of participating physicians
      indicated significant improvements in clinical knowledge and appropriate
      antibiotic treatment of upper respiratory tract infections. Overall rates of
      antibiotic use in the province have stabilized since 2006. The rates of
      consumption of fluoroquinolones and macrolides have levelled off since 2005.
      Utilization rates for acute bronchitis are at the same level as when the program
      was first implemented, but rates for other acute upper respiratory tract
      infections of interest have declined. CONCLUSIONS: The Do Bugs Need Drugs?
      program significantly improves physician antibiotic prescription decisions and is
      ecologically associated with desirable change in population antibiotic
      consumption patterns.

PMID- 22379485
TI  - Evaluation of influenza-specific humoral response by microbead array analysis.
AB  - RATIONALE: Quantitation and determination of antigen specificity of systemic and
      mucosal immune responses to influenza vaccination is beneficial for future
      vaccine development. Previous methods to acquire this information were costly,
      time consuming and sample exhaustive. The benefits of suspension microbead array
      (MBA) analysis are numerous. The multiplex capabilities of the system conserve
      time, money and sample, while generating statistically powerful data. OBJECTIVE:
      To demonstrate the use of the assay by comparing the humoral influenza-specific
      responses of two cohorts from two countries that differed in circulating
      influenza strains and rates of influenza vaccination. METHODS: Influenza
      hemagglutinin (HA) from different strains were coated on microbeads and incubated
      with serum samples to capture immunoglobulin (Ig) A(1) and IgG(1) host
      antibodies. RESULTS: Statistically significant differences in IgA(1) and IgG(1)
      exist between the serum samples from Winnipeg (Manitoba) donors and those from
      Kenyan (Africa) donors. Data were compared using Mann-Whitney nonparametric
      tests. The Winnipeg donors had higher mean fluorescence intensity values, with
      significant P values for anti-HA IgA(1) to A/Wyoming/3/2003 (P=0.044),
      A/Vietnam/1203/2004 (P=0.0179), A/New Caledonia/20/99 (P<0.0001) and
      B/Tokyo/53/99 (P=0.0002). No differences were seen between the groups in their
      response to B/Jilin/20/2003. The Winnipeg donors had higher mean fluorescence
      intensity values, with significant P values for anti-HA IgG(1) to
      A/Wyoming/3/2003 (P=0.0135), B/Tokyo/53/99 (P=0.006) and B/Jilin20/2003
      (P=0.026). CONCLUSION: Influenza-specific IgA(1) and IgG(1) antibodies were
      successfully detected using MBA technology. A significant difference in antibody
      response was observed between Winnipeg and Kenyan donor serums. MBA analysis is a
      relatively quick and cost-effective method for serum antibody analysis. The
      potential to simultaneously assay small sample volumes for a multitude of
      antigens makes this method invaluable for future vaccine response monitoring.

PMID- 22379486
TI  - The role of the third acid-fast bacillus smear in tuberculosis screening for
      infection control purposes: A controversial topic revisited.
AB  - INTRODUCTION: Recent studies have suggested that two negative acid-fast bacillus
      (AFB) smears may be as effective as three when screening patients with suspected
      Mycobacterium tuberculosis for respiratory isolation purposes. However, current
      recommendations in Canada, the United States and Europe still support a three
      smear approach. METHODS: The microbiology database of a tertiary care hospital
      was searched for sputum, tracheal aspirates and bronchoalveolar lavage samples
      from 2003 to 2007 that had been sent for mycobacterial testing. The first patient
      specimen to become AFB smear positive was noted. As well, the time required to
      collect the third specimen in hospitalized patients who remained smear negative
      was used to estimate the savings in isolation costs associated with a two-smear
      approach. RESULTS: There were 8347 respiratory specimens from 5168 patients in
      the five-year period. Of these patients, 2.2% (116 of 5168) were AFB smear
      positive, of whom 55.2% (64 of 116) were culture positive for Mycobacterium
      tuberculosis. Overall 89% (57 of 64) of patients were identified as being AFB
      smear positive by the first smear, 7.8% (five of 64) were identified by the
      second smear and 3.2% (two of 64) were identified by further smears. Smear
      negative patients spent a combined 710 days in isolation awaiting collection of
      the third sample at a cost of approximately $142,000 over five years. CONCLUSION:
      A two-smear approach for discontinuation of respiratory isolation precautions is
      safe and has the potential to reduce hospital expenditures.

PMID- 22379487
TI  - Vascular nosocomial Nocardia farcinica infection after arterial stenting in an
      immunocompetent patient.

PMID- 22379488
TI  - Province-wide adenovirus type 3 outbreak with severe cases in New Brunswick.
AB  - Adenovirus is a commonly isolated virus in clinical samples. Life-threatening
      infections, although rare, are described worldwide. An epidemic spread of an
      adenovirus type 3 strain occurred in the province of New Brunswick during the
      fall of 2008 to the winter of 2009; it resulted in three severely ill patients,
      with one fatality. Adenovirus should be considered as a cause of severe community
      acquired viral pneumonia, especially when the influenza test is negative.

PMID- 22379489
TI  - A case of acute cholecystitis caused by methicillin-resistant Staphylococcus
      aureus in an immunocompromised patient.
AB  - Although infections with Staphylococcus aureus can implicate multiple organ
      systems, involvement of the biliary tract is rare. A case of acute cholecystitis
      and bacteremia with methicillin-resistant S aureus (MRSA) in a patient with HIV
      infection is presented. The MRSA isolate was found to be a community-associated
      strain. The present case highlights the invasive nature of staphylococcal
      infections and the emerging importance of community-associated MRSA strains.

PMID- 22379490
TI  - Photooxidation of metal-bound thiolates: reactivity of sulfur containing
      peroxidic intermediates.
AB  - A variety of reactions of singlet oxygen with metal-bound thiolates are
      described, and contrasted with the photooxidation of organic sulfides.
      Superficially, these two processes appear to involve similar mechanisms, but
      there are important differences: unlike the photooxidation of organic sulfides,
      the rate of the initial reaction of metal-thiolates with singlet oxygen (k(t))
      appears to be affected by protic solvents and acids. The nucleophilicity of the
      thiolate moiety is reduced by addition of acids or in protic solvents, leading to
      significantly lower k(t) values. The primary intermediate in the photooxidation
      of organic sulfides is a nucleophilic persulfoxide, which can be stabilized by
      protic solvents or by addition of acid. However, the primary intermediate in the
      photooxidation of metal thiolates cannot be trapped with phosphite, suggesting
      that it may be less nucleophilic than its organic counterpart. Support for this
      hypothesis is also derived from the rather modest (compared with organic
      sulfides) acceleration of the rate of product formation by addition of acid.

PMID- 22379491
TI  - Transitory behaviors in diffusively coupled nonlinear oscillators.
AB  - We study collective behaviors of diffusively coupled oscillators which exhibit
      out-of-phase synchrony for the case of weakly interacting two oscillators. In
      large populations of such oscillators interacting via one-dimensionally nearest
      neighbor couplings, there appear various collective behaviors depending on the
      coupling strength, regardless of the number of oscillators. Among others, we
      focus on an intermittent behavior consisting of the all-synchronized state, a
      weakly chaotic state and some sorts of metachronal waves. Here, a metachronal
      wave means a wave with orderly phase shifts of oscillations. Such phase shifts
      are produced by the dephasing interaction which produces the out-of-phase
      synchronized states in two coupled oscillators. We also show that the
      abovementioned intermittent behavior can be interpreted as in-out intermittency
      where two saddles on an invariant subspace, the all-synchronized state and one of
      the metachronal waves play an important role.

PMID- 22379492
TI  - Local synchronization of one-to-one coupled neural networks with discontinuous
      activations.
AB  - In this paper, local synchronization is considered for coupled delayed neural
      networks with discontinuous activation functions. Under the framework of Filippov
      solution and in the sense of generalized derivative, a novel sufficient condition
      is obtained to ensure the synchronization based on the Lyapunov exponent and the
      detailed analysis in Danca (Int J Bifurcat Chaos 12(8):1813-1826, 2002; Chaos
      Solitons Fractals 22:605-612, 2004). Simulation results are given to illustrate
      the theoretical results.

PMID- 22379493
TI  - Single tap identification for fast BCI control.
AB  - One of the major aims of BCI research is devoted to achieving faster and more
      efficient control of external devices. The identification of individual tap
      events in a motor imagery BCI is therefore a desirable goal. EEG is recorded from
      subjects performing and imagining finger taps with their left and right hands. A
      Differential Evolution based feature selection wrapper is used in order to
      identify optimal features in the spatial and frequency domains for tap
      identification. Channel-frequency band combinations are found which allow
      differentiation of tap vs. no-tap control conditions for executed and imagined
      taps. Left vs. right hand taps may also be differentiated with features found in
      this manner. A sliding time window is then used to accurately identify individual
      taps in the executed tap and imagined tap conditions. Highly statistically
      significant classification accuracies are achieved with time windows of 0.5 s and
      more allowing taps to be identified on a single trial basis.

PMID- 22379494
TI  - Perceptual learning with perceptions.
AB  - In this work we present an approach to understand neuronal mechanisms underlying
      perceptual learning. Experimental results achieved with stimulus patterns of
      coherently moving dots are considered to build a simple neuronal model. The
      design of the model is made transparent and underlying behavioral assumptions
      made explicit. The key aspect of the suggested neuronal model is the learning
      algorithm used: We evaluated an implementation of Hebbian learning and are thus
      able to provide a straight-forward model capable to explain the neuronal dynamics
      underlying perceptual learning. Moreover, the simulation results suggest a very
      simple explanation for the aspect of "sub-threshold" learning (Watanabe et al. in
      Nature 413:844-884, 2001) as well as the relearning of motion discrimination
      after damage to primary visual cortex as recently reported (Huxlin et al. in J
      Neurosci 29:3981-3991, 2009) and at least indicate that perceptual learning might
      only occur when accompanied by conscious percepts. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11571-010-9134-9)
      contains supplementary material, which is available to authorized users.

PMID- 22379495
TI  - Transient coordinated activity within the developing brain's default network.
AB  - The concept of a brain default network postulates that specific brain regions are
      more active when a person is engaged in introspective mental activity. Transient
      functional coordination between groups of neurons is thought to be necessary for
      information processing. Since children develop introspection as they mature,
      regions of the default network may establish increasing functional coordination
      with age, resulting in fewer fluctuations in synchronization patterns. We
      investigated the transient coordinated activity in regions of the default network
      in seventeen children aged 11 months to 17 years of age using EEG recordings
      while subjects were resting quietly with eyes closed. The temporal and spatial
      fluctuations in the phase synchrony patterns were estimated across sites
      associated with the default network pattern and compared to other regions. Lower
      variability of the spatio-temporal patterns of phase synchronization associated
      with the default network was observed in the older group as compared to the
      younger group. This indicates that functional coordination increases among
      regions of the default network as children develop.

PMID- 22379496
TI  - Distinct dynamical patterns that distinguish willed and forced actions.
AB  - The neural pathways for generating willed actions have been increasingly
      investigated since the famous pioneering work by Benjamin Libet on the nature of
      free will. To better understand what differentiates the brain states underlying
      willed and forced behaviours, we performed a study of chosen and forced actions
      over a binary choice scenario. Magnetoencephalography recordings were obtained
      from six subjects during a simple task in which the subject presses a button with
      the left or right finger in response to a cue that either (1) specifies the
      finger with which the button should be pressed or (2) instructs the subject to
      press a button with a finger of their own choosing. Three independent analyses
      were performed to investigate the dynamical patterns of neural activity
      supporting willed and forced behaviours during the preparatory period preceding a
      button press. Each analysis offered similar findings in the temporal and spatial
      domains and in particular, a high accuracy in the classification of single trials
      was obtained around 200 ms after cue presentation with an overall average of 82%.
      During this period, the majority of the discriminatory power comes from
      differential neural processes observed bilaterally in the parietal lobes, as well
      as some differences in occipital and temporal lobes, suggesting a contribution of
      these regions to willed and forced behaviours.

PMID- 22379497
TI  - Online learning and stimulus-driven responses of neurons in visual cortex.
AB  - In understanding how visual scene is processed in visual cortex, it has been an
      intriguing problem for theoretical and experimental neuroscientists to examine
      the relationship between visual stimuli and the induced responses of visual
      cortex. In particular, it is less explored whether and how the collective
      responses of visual neurons are patterned to reflect the geometrical
      regularities. In this paper, through a computation model and statistical
      analysis, we show that the orientation preference maps induced from correlated
      visual stimuli exhibit geometrical regularities similar as observed in natural
      images.

PMID- 22379498
TI  - Exponential decay characteristics of the stochastic integer multiple neural
      firing patterns.
AB  - Integer multiple neural firing patterns exhibit multi-peaks in inter-spike
      interval (ISI) histogram (ISIH) and exponential decay in amplitude of peaks,
      which results from their stochastic mechanisms. But in previous experimental
      observation that the decay in ISIH frequently shows obvious bias from exponential
      law. This paper studied three typical cases of the decay, by transforming ISI
      series of the firing to discrete binary chain and calculating the probabilities
      or frequencies of symbols over the whole chain. The first case is the exponential
      decay without bias. An example of this case was discovered on hippocampal CA1
      pyramidal neuron stimulated by external signal. Probability calculation shows
      that this decay without bias results from a stochastic renewal process, in which
      the successive spikes are independent. The second case is the exponential decay
      with a higher first peak, while the third case is that with a lower first peak.
      An example of the second case was discovered in experiment on a neural pacemaker.
      Simulation and calculation of the second and third cases indicate that the
      dependency in successive spikes of the firing leads to the bias seen in decay of
      ISIH peaks. The quantitative expression of the decay slope of three cases of
      firing patterns, as well as the excitatory effect in the second case of firing
      pattern and the inhibitory effect in the third case of firing pattern are
      identified. The results clearly reveal the mechanism of the exponential decay in
      ISIH peaks of a number of important neural firing patterns and provide new
      understanding for typical bias from the exponential decay law.

PMID- 22379499
TI  - Neurofunctional model of large-scale correlates of selective attention governed
      by stimulus-novelty.
AB  - Multiple studies demonstrate the influence of the limbic system on the processing
      of sensory events and attentional guidance. But the mechanisms involved therein
      are yet not entirely clear. The close connection of handling incoming sensory
      information and memory retrieval, like in the case of habituation towards
      insignificant stimuli, suggests a crucial impact of the hippocampus on the
      direction of attention. In this paper we thus present a neurofunctional forward
      model of a hippocampal comparator function based on the theory of theta-regulated
      attention. Subsequently we integrated this comparator model into a multiscale
      framework for the simulation of evoked responses. The results of our simulations
      were compared to experimental data on electroencephalographic (EEG) correlates of
      habituation towards familiar stimuli using time-scale analysis. In consequence we
      are able to present additional evidence for limbic influences on the direction of
      attention driven by stimulus novelty and a systems neuroscience framework for the
      statements given in the theta-regulated attention hypothesis.

PMID- 22379501
TI  - A retrospective review of malignant minor salivary gland tumors and a proposed
      protocol for future care.
AB  - Malignant tumors affecting minor salivary glands present a wide range of
      histopathologic types. The present study sought to design a protocol for
      management of patients with malignancy of minor salivary glands. The data of 22
      patients with malignant tumors of the minor salivary glands, surgically treated
      at our department in the past 10 years, were accumulated and studied. All
      patients underwent a diagnostic workup prior to surgery. The most useful
      examinations were magnetic resonance imaging of the head and neck and
      computerized tomography of the thorax. Wide local excision was sufficient for the
      majority of patients. Adjuvant treatment is indicated for high-grade, tumor
      positive lymph nodes and residual disease. Malignant tumors of minor salivary
      glands are very rare. Therefore, design of management protocols is challenging.
      Management of the neck is necessary in evidence of metastasis and in high-grade
      and advanced-stage disease. Adjuvant treatment should be included in the
      treatment protocol in certain indications. Most importantly, long-term follow up
      is very important for all patients with malignant minor salivary tumors.

PMID- 22379500
TI  - Circulating MicroRNA as Biomarkers: An Update in Prostate Cancer.
AB  - Prostate cancer (PCa) is the most common non-skin cancer among men. Currently
      available diagnostic tests for PCa are inadequate in terms of low specificity and
      poor sensitivity. microRNAs offer a hope to overcome these drawbacks by virtue of
      their cancer specific expression and high stability. They can readily be detected
      and quantified in frozen and as well as formalin-fixed paraffin-embedded tissues.
      Observation of circulating miRNA in serum/plasma samples and other body fluids
      holds a promise to quickly move from research and provide a biomolecule of
      clinical relevance and an improvement over presently available biomarkers. This
      review highlights the potential role of circulating miRNAs as molecular markers
      for cancer and as targets for therapeutic manipulation. Further, this review
      summarizes the current understanding of various circulating miRNA with respect to
      prostate cancer. To conclude, circulating miRNAs are an active area of current
      investigation and holds promise to serve a wide range of clinical applications
      and unwrap a new era in cancer diagnosis and therapeutics.

PMID- 22379502
TI  - Bilateral mandibular condylysis from systemic sclerosis: case report of surgical
      correction with bilateral total temporomandibular joint replacement.
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown
      etiology. The hallmark of SSc is scleroderma, referring to the presence of
      thickened, hardened skin. Oral and maxillofacial manifestations of the disease
      are numerous including masklike appearance, trismus, muscular atrophy, thin
      atrophied lips, secondary microstomia, xerostomia, rigidity of tongue and lips,
      widening of the periodontal ligament space, trigeminal neuralgia, and resorption
      of the mandible. A 35-year-old woman with limited cutaneous SSc presented with
      bilateral mandibular condylysis, severe class II mandibular deficiency, and large
      anterior open bite and limited range of mandibular opening at 27 mm. Surgical
      correction consisted of bilateral total temporomandibular joint reconstruction
      with stock prostheses combined with Le Fort I maxillary impaction and functional
      advancement genioplasty. This resulted in a functional occlusion with elimination
      of her open bite and a more esthetic profile. Her occlusion has remained stable
      at 7 months. The incidence of mandibular resorption in SSc has been found to be
      20% to 33%. The mandibular angles are most commonly involved (37.6%), followed by
      the condyle (20.8%), coronoid process (20.0%), and the posterior border of the
      ascending ramus (14.4%). Bilateral condylysis is present in 13.7% of the cases.
      Very few cases of surgical correction of malocclusion induced by SSc-related
      condylysis have been reported in the literature. To the best of our knowledge,
      this is the first case report of bilateral condylysis from SSc where surgical
      replacement of the resorbed condyles was attempted. Bilateral total
      temporomandibular joint replacement can give these patients a functional
      occlusion, improved facial balance, and improved quality of life.

PMID- 22379503
TI  - Different surgical approaches for multiple fractured atrophic mandibles.
AB  - Atrophic edentulous mandible fractures in geriatric patients have low incidence
      but present several biological and biomechanical peculiarities that produce a
      nonunion rate of around 20%. Surgical extraoral approaches for internal fixation
      of these fractures can be transcervical or by one or two submandibular incisions.
      Two patients sustaining multiple fractures in atrophic edentulous mandible are
      presented: the first patient was 72-years-old, treated by two submandibular
      incisions, and the second was 81-years-old, treated by transcervical approach. We
      discuss the advantages and drawbacks of each approach and their indications
      according to the Luhr et al (1996) atrophy index.

PMID- 22379504
TI  - Free flap reconstruction of self-inflicted submental gunshot wounds.
AB  - In this study, we review outcomes for 15 patients with self-inflicted submental
      gunshot wounds requiring free flap reconstruction. Patients presented to two
      tertiary care centers over a 7-year period. Mean age was 46 years (range, 16 to
      76 years), 67% (n = 10) had a psychiatric history, and four were known to abuse
      illicit substances. Patients with oromandibular involvement required on average a
      total of 2.8 procedures, and those with midface (3.7) or combined defects (6)
      required more total procedures (p = 0.21). Donor sites included osteocutaneous
      radial forearm (n = 8), fibula (n = 4), fasciocutaneous radial forearm (n = 5),
      and anterior lateral thigh (n = 1). Median length of hospitalization was 8 days.
      Overall complication rate was 33% (n = 5), and included hematoma (n = 1), fistula
      (n = 1), and mandibular malunion (n = 2). Most patients were able to tolerate a
      regular or soft diet (92%), maintain oral competency (58%), and demonstrate
      intelligible speech (92%) at a median time to follow-up of 12 months. Despite the
      devastating nature of this injury, free flap reconstruction of self-inflicted
      submental gunshot wounds results in acceptable functional results for the
      majority of patients.

PMID- 22379505
TI  - Long-Term Follow-up of a Tessier Number 5 Facial Cleft.
AB  - The Tessier number 5 cleft is a rare craniofacial anomaly. Although there are
      case reports outlining various methods of primary surgical repair and outcomes,
      few cases reveal long-term follow-up or discuss secondary reconstruction. This
      article presents the case of a man born with a unilateral Tessier number 5 cleft
      who presented to our institution at the age of 41 after more than 25 previous
      surgeries. Over the course of 11 years, he had several surgeries including an
      orbital repositioning through a combined intra- and extracranial approach, an
      orbital enucleation, and an anterolateral thigh flap. The patient was fitted with
      an orbital prosthesis and a satisfactory aesthetic result was achieved.

PMID- 22379506
TI  - Pediatric facial fractures and potential long-term growth disturbances.
AB  - Fractures of the pediatric craniofacial skeleton can be challenging to manage.
      The initial injury and subsequent treatment can cause long-term growth
      disturbances yielding problematic secondary deformities. This review considers
      the normal growth of the craniofacial skeleton and typical facial fracture
      presentations in children and discusses the potential long-term sequelae from
      these injuries and their management.

PMID- 22379507
TI  - Nasal foreign bodies: a review of management strategies and a clinical scenario
      presentation.
AB  - We report a case of a toothbrush head lodged into the nasal cavity, which
      required an external rhinoplasty for retrieval. A review of the literature on
      management strategies in case of nasal foreign bodies is presented.

PMID- 22379508
TI  - Supraorbital Rim Contour Restoration with Porous Polyethylene Implant via
      Preexisting Scar.

PMID- 22379509
TI  - Do the Most Vulnerable People Live in the Worst Slums? A Spatial Analysis of
      Accra, Ghana.
AB  - Slums are examples of localized communities within third world urban systems
      representing a range of vulnerabilities and adaptive capacities. This study
      examines vulnerability in relation to flooding, environmental degradation, social
      status, demographics, and health in the slums of Accra, Ghana by utilizing a
      place-based approach informed by fieldwork, remote sensing, census data, and
      geographically weighted regression. The study objectives are threefold: (1) to
      move slums from a dichotomous into a continuous classification and examine the
      spatial patterns of the gradient, (2) develop measures of vulnerability for a
      developing world city and model the relationship between slums and vulnerability,
      and (3) to assess if the most vulnerable individuals live in the worst slums. A
      previously developed slum index is utilized, and four new measures of
      vulnerability are developed through principle components analysis, including a
      novel component of health vulnerability based on child mortality. Visualizations
      of the vulnerability measures assess spatial patterns of vulnerability in Accra.
      Ordinary least squares, spatial, and geographically weighted regression model the
      ability of the slum index to predict the four vulnerability measures. The slum
      index performs well for three of the four vulnerability measures, but is least
      able to predict health vulnerability underscoring the complex relationship
      between slums and child mortality in Accra. Finally, quintile analysis
      demonstrates the elevated prevalence of high vulnerability in places with high
      slum index scores.

PMID- 22379511
TI  - Irb 101.

PMID- 22379510
TI  - Education Research and Human Subject Protection: Crossing the IRB Quagmire.

PMID- 22379513
TI  - Is it Right to Measure the Productivity of Senior Clinician/Educators by Relative
      Value Units?

PMID- 22379514
TI  - The roots of discontent: understanding the pressures of psychiatric emergency
      training.

PMID- 22379515
TI  - Practice-based learning and improvement curricula: a critical opportunity to
      educate future physicians and leaders.

PMID- 22379516
TI  - Changing the formula of residents' work hours in internal medicine: moving from
      "years in training" to "hours in training".
AB  - BACKGROUND: In a recent report, the Institute of Medicine recommended more
      restrictions on residents' working hours. Several problems exist with a system
      that places a weekly limit on resident duty hours: (1) it assumes the presence of
      a linear relationship between hours of work and patient safety; (2) it fails to
      consider differences in intensity among programs; and (3) it does not address
      increases in the scientific content of medicine, and it places the burden of
      enforcing the duty hour limits on the Accreditation Council for Graduate Medical
      Education. PROPOSAL: An innovative method of calculating credit hours for
      graduate medical education would shift the focus from "years of residency" to
      "hours of residency." For example, internal medicine residents would be requested
      to spend 8640 hours of total training hours (assuming 60 hours per week for 48
      weeks annually) instead of the traditional 3 years. This method of counting
      training hours is used by other professions, such as the Intern Development
      Program of the National Council of Architectural Registration Boards. The
      proposed approach would allow residents and program directors to pace training
      based on individual capabilities. Standards for resident education should include
      the average number of patients treated in each setting (inpatient or outpatient).
      A possible set of "multipliers" based on these parameters, and possibly others
      such as resident evaluation, is devised to calculate the "final adjusted
      accredited hours" that count toward graduation. ANTICIPATED BENEFITS:
      Substituting "years of training" with "hours of training" may resolve many of the
      concerns with the current residency education model, as well as adapt to the
      demands of residents' personal lives. It also may allow residents to pace their
      training according to their capabilities and learning styles, and contribute to
      reflective learning and better quality education.

PMID- 22379517
TI  - Two perspectives on the educational and administrative roles of the pediatric
      chief resident.
AB  - PURPOSE: To investigate pediatric chief residents' responsibilities and determine
      how chief residents and program directors view the scope of the chief resident's
      role. SURVEY: We distributed a 20-item survey to program directors and chief
      residents at all US pediatric residency programs. Questions pertained to
      activities performed and the level of importance of administrative, clinical, and
      educational activities. The survey also investigated motivating factors to become
      chief resident, future career plans, and level of job satisfaction. RESULTS: We
      received responses from 127 program directors and 101 chief residents. Of the
      chief residents, 98% (99/101) felt administrative tasks were very/somewhat
      important, followed by education, service, and research. Significantly more
      program directors than chief residents felt chiefs' overall workload was well
      balanced. Program directors gave higher ratings than chief residents on chief's
      ability to develop clinical skills (79% [95/121] versus 61% [61/100]) and manage
      stress and burnout (86% [104/121] versus 72% [72/100]). Future career plans for
      chief residents in decreasing order included fellowship, outpatient practice,
      academic practice, and working as a hospitalist. The most significant problems
      reported by the chief residents were lack of administrative support and lack of
      time spent in educational/clinical activities. CONCLUSIONS: The chief resident
      role is primarily administrative, but program directors and chiefs feel teaching
      and clinical responsibilities also are important. Although the 2 groups agreed in
      many areas, program directors underestimated the administrative demands placed on
      the chief residents, and our findings suggest the chief resident role may be more
      fulfilling if the balance was shifted somewhat toward teaching and clinical
      responsibilities.

PMID- 22379518
TI  - A preliminary report on resident emergency psychiatry training from a survey of
      psychiatry chief residents.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      requirements stipulate that psychiatry residents need to be educated in the area
      of emergency psychiatry. Existing research investigating the current state of
      this training is limited, and no research to date has assessed whether the ACGME
      Residency Review Committee requirements for psychiatry residency training are
      followed by psychiatry residency training programs. METHODS: We administered, to
      chief resident attendees of a national leadership conference, a 24-item paper
      survey on the types and amount of emergency psychiatry training provided by their
      psychiatric residency training programs. Descriptive statistics were used in the
      analysis. RESULTS: Of 154 surveys distributed, 111 were returned (72% response
      rate). Nearly one-third of chief resident respondents indicated that more than
      50% of their program's emergency psychiatry training was provided during on-call
      periods. A minority indicated that they were aware of the ACGME program
      requirements for emergency psychiatry training. While training in emergency
      psychiatry occurred in many programs through rotations-different from the on-call
      period-direct supervision was available during on-call training only about one
      third of the time. CONCLUSIONS: The findings suggest that about one-third of
      psychiatry residency training programs do not adhere to the ACGME standards for
      emergency psychiatry training. Enhanced knowledge of the ACGME requirements may
      enhance psychiatry residents' understanding on how their programs are fulfilling
      the need for more emergency psychiatry training. Alternative settings to the on
      call period for emergency psychiatry training are more likely to provide for
      direct supervision.

PMID- 22379519
TI  - Resident training in the psychiatric emergency service: duty hours tell only part
      of the story.
AB  - BACKGROUND: Psychiatry residents in North America are generally required to work
      on-call on the psychiatric emergency service (PES) during training. Resident
      discontent with the long hours, onerous case loads, and lack of on-call teaching
      has been reported as a barrier to PES training. Given that the PES is a
      longitudinal and important experience, we sought to develop a better
      understanding of this service from the resident perspective and identify factors
      that affect residents as they work and train in this area. METHODS: In this
      grounded theory qualitative study, we collected data from focus groups with
      psychiatry residents. We analyzed data according to grounded theory methodology
      to develop an enhanced understanding of the resident experience on the PES.
      RESULTS: THREE MAJOR THEMES EMERGED FROM DATA ANALYSIS: (1) challenges residents
      face in the PES are complex and attributable to more than simply long duty hours,
      (2) the PES offers unique learning opportunities for residents, and (3) resident
      satisfaction with the PES depends on a good relationship with the team.
      CONCLUSIONS: This study highlights important topics for any residency programs
      that require residents to work on a PES team. Although much attention has been
      paid to addressing challenges inherent to the on-call experience, such as
      limiting the amount of on-call hours and call frequency, equal attention should
      be paid to team dynamics. Like prior work on physician contentment and
      multidisciplinary team functioning, our study found that physicians will tolerate
      stressful workplace factors, so long as there is a supportive and healthy team
      dynamic. It is important for program directors to identify problems with team
      dynamics in the PES in light of their potential impact on residents.

PMID- 22379520
TI  - Key elements of clinical physician leadership at an academic medical center.
AB  - BACKGROUND: A considerable body of literature in the management sciences has
      defined leadership and how leadership skills can be attained. There is
      considerably less literature about leadership within medical settings. Physicians
      in-training are frequently placed in leadership positions ranging from running a
      clinical team or overseeing a resuscitation effort. However, physicians-in
      training rarely receive such training. The objective of this study was to
      discover characteristics associated with effective physician leadership at an
      academic medical center for future development of such training. METHODS: We
      conducted focus groups with medical professionals (attending physicians,
      residents, and nurses) at an academic medical center. The focus group discussion
      script was designed to elicit participants' perceptions of qualities necessary
      for physician leadership. The lead question asked participants to imagine a
      scenario in which they either acted as or observed a physician leader. Two
      independent reviewers reviewed transcripts to identify key domains of physician
      leadership. RESULTS: Although the context was not specified, the focus group
      participants discussed leadership in the context of a clinical team. They
      identified 4 important themes: management of the team, establishing a vision,
      communication, and personal attributes. CONCLUSIONS: Physician leadership exists
      in clinical settings. This study highlights the elements essential to that
      leadership. Understanding the physician attributes and behaviors that result in
      effective leadership and teamwork can lay the groundwork for more formal
      leadership education for physicians-in-training.

PMID- 22379521
TI  - Residents' self-perceived errors in transitions of care in the emergency
      department.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education requirements
      for systems-based practice state residents are expected to participate in
      identifying system errors and implementing potential systems solutions. The
      objective of this study was to determine the numbers of perceived errors
      occurring from patient pass offs between resident physicians in our emergency
      department. METHODS: Using a prospective observational study, we queried
      emergency medicine residents about perceived errors in the transition of care
      using trained research assistants and a standardized protocol. Transition of care
      was defined as the transfer of responsibility to evaluate and treat and
      disposition of a patient in the emergency department from 1 resident physician to
      a second oncoming emergency department resident physician. Mean resident
      perceived errors per shift and per patient transfer of care were calculated.
      Additionally, the mean number of perceived errors impacting patients was
      calculated. RESULTS: Emergency medicine residents on 107 shifts reported
      receiving 713 patients in pass off with a mean of 7 patients per physician per
      shift, with 40% of patients passed off needing some intervention (mean of 2.8
      patients per provider per shift). Nineteen of the 107 shifts (17.8%) during which
      a resident took patients from a prior provider had a perceived error in at least
      1 patient signed off. Of the 713 patients transitioned, the receiving physician
      perceived an error related to the transition of care for 23. Two of the 23 errors
      were determined by reviewing emergency medicine attendings to not be errors, and
      for 9 the receiving physician perceived an impact on the patient. All were delays
      in care or disposition. CONCLUSION: Our data suggest emergency medicine residents
      were able to perceive errors related to transitions of care, describe the types
      of pass-off errors, and, to a lesser degree, describe the impact these errors
      have on patients.

PMID- 22379522
TI  - Development and preliminary evaluation of a practice-based learning and
      improvement tool for assessing resident competence and guiding curriculum
      development.
AB  - BACKGROUND: Although practice-based learning and improvement (PBLI) is now
      recognized as a fundamental and necessary skill set, we are still in need of
      tools that yield specific information about gaps in knowledge and application to
      help nurture the development of quality improvement (QI) skills in physicians in
      a proficient and proactive manner. We developed a questionnaire and coding system
      as an assessment tool to evaluate and provide feedback regarding PBLI self
      efficacy, knowledge, and application skills for residency programs and related
      professional requirements. METHODS: Five nationally recognized QI experts/leaders
      reviewed and completed our questionnaire. Through an iterative process, a coding
      system based on identifying key variables needed for ideal responses was
      developed to score project proposals. The coding system comprised 14 variables
      related to the QI projects, and an additional 30 variables related to the core
      knowledge concepts related to PBLI. A total of 86 residents completed the
      questionnaire, and 2 raters coded their open-ended responses. Interrater
      reliability was assessed by percentage agreement and Cohen kappa for individual
      variables and Lin concordance correlation for total scores for knowledge and
      application. Discriminative validity (t test to compare known groups) and
      coefficient of reproducibility as an indicator of construct validity (item
      difficulty hierarchy) were also assessed. RESULTS: Interrater reliability
      estimates were good (percentage of agreements, above 90%; kappa, above 0.4 for
      most variables; concordances for total scores were R  =  .88 for knowledge and R 
      =  .98 for application). CONCLUSION: Despite the residents' limited range of
      experiences in the group with prior PBLI exposure, our tool met our goal of
      differentiating between the 2 groups in our preliminary analyses. Correcting for
      chance agreement identified some variables that are potentially problematic.
      Although additional evaluation is needed, our tool may prove helpful and provide
      detailed information about trainees' progress and the curriculum.

PMID- 22379523
TI  - Pilot study evaluating a practice-based learning and improvement curriculum
      focusing on the development of system-level quality improvement skills.
AB  - BACKGROUND: We developed a practice-based learning and improvement (PBLI)
      curriculum to address important gaps in components of content and experiential
      learning activities through didactics and participation in systems-level quality
      improvement projects that focus on making changes in health care processes.
      METHODS: We evaluated the impact of our curriculum on resident PBLI knowledge,
      self-efficacy, and application skills. A quasi-experimental design assessed the
      impact of a curriculum (PBLI quality improvement systems compared with non-PBLI)
      on internal medicine residents' learning during a 4-week ambulatory block. We
      measured application skills, self-efficacy, and knowledge by using the Systems
      Quality Improvement Training and Assessment Tool. Exit evaluations assessed time
      invested and experiences related to the team projects and suggestions for
      improving the curriculum. RESULTS: The 2 groups showed differences in change
      scores. Relative to the comparison group, residents in the PBLI curriculum
      demonstrated a significant increase in the belief about their ability to
      implement a continuous quality improvement project (P  =  .020), comfort level in
      developing data collection plans (P  =  .010), and total knowledge scores (P <
      .001), after adjusting for prior PBLI experience. Participants in the PBLI
      curriculum also demonstrated significant improvement in providing a more complete
      aim statement for a proposed project after adjusting for prior PBLI experience (P
      =  .001). Exit evaluations were completed by 96% of PBLI curriculum participants
      who reported high satisfaction with team performance. CONCLUSION: Residents in
      our curriculum showed gains in areas fundamental for PBLI competency. The
      observed improvements were related to fundamental quality improvement knowledge,
      with limited gain in application skills. This suggests that while heading in the
      right direction, we need to conceptualize and structure PBLI training in a way
      that integrates it throughout the residency program and fosters the application
      of this knowledge and these skills.

PMID- 22379524
TI  - Numerical Versus Pass/Fail Scoring on the USMLE: What Do Medical Students and
      Residents Want and Why?
AB  - BACKGROUND: Although the primary purpose of the US Medical Licensing Examination
      (USMLE) is assessment for licensure, USMLE scores often are used for other
      purposes, more prominently resident selection. The Committee to Evaluate the
      USMLE Program currently is considering a number of substantial changes, including
      conversion to pass/fail scoring. METHODS: A survey was administered to third-year
      (MS3) and fourth-year (MS4) medical students and residents at a single
      institution to evaluate opinions regarding pass/fail scoring on the USMLE.
      RESULTS: Response rate was 59% (n  =  732 of 1249). Reported score distribution
      for Step 1 was 30% for <220, 38% for 220-240, and 32% for >240, with no
      difference between MS3s, MS4s, and residents (P  =  .89). Score distribution for
      Step 2 Clinical Knowledge (CK) was similar. Only 26% of respondents agreed that
      Step 1 should be pass/fail; 38% agreed with pass/fail scoring for Step 2 CK.
      Numerical scoring on Step 1 was preferred by respondents who: (1) agreed that the
      examination gave an accurate estimate of knowledge (odds ratio [OR], 4.23;
      confidence interval [CI], 2.41-7.43; P < .001); (2) scored >240 (OR, 4.0; CI,
      1.92-8.33; P < .001); and (3) felt that acquisition of knowledge might decrease
      if the examination were pass/fail (OR, 10.15; CI, 3.32-31.02; P < .001). For Step
      2 CK, numerical scoring was preferred by respondents who: (1) believed they
      gained a large amount of knowledge preparing for the examination (OR, 2.63; CI,
      1.52-4.76; P < .001); (2) scored >240 (OR, 4.76; CI, 2.86-8.33; P < .001); (3)
      felt that the amount of knowledge acquired might decrease if it were pass/fail
      (OR, 28.16; CI, 7.31-108.43; P < .001); and (4) believed their Step 2 CK score
      was important when applying for residency (OR, 2.37; CI, 1.47-3.84; P < .001).
      CONCLUSIONS: Students and residents prefer the ongoing use of numerical scoring
      because they believe that scores are important in residency selection, that
      residency applicants are advantaged by examination scores, and that scores
      provide an important impetus to review and solidify medical knowledge.

PMID- 22379525
TI  - Feasibility of an internet-based global ranking instrument.
AB  - BACKGROUND: Single-item global ratings are commonly used at the end of
      undergraduate clerkships and residency rotations to measure specific competencies
      and/or to compare the performances of individuals against their peers. We
      hypothesized that an Internet-based instrument would be feasible to adequately
      distinguish high- and low-ability residents. MATERIALS AND METHODS: After
      receiving Institutional Review Board approval, we developed an Internet-based
      global ranking instrument to rank 42 third-year residents (21 in 2008 and 21 in
      2009) in a major university teaching hospital's department of anesthesiology.
      Evaluators were anesthesia attendings and nonphysicians in 3 tertiary-referral
      hospitals. Evaluators were asked this ranking question: "When it comes to overall
      clinical ability, how does this individual compare to all their peers?" RESULTS:
      For 2008, 111 evaluators completed the ranking exercise; for 2009, 79 completed
      it. Residents were rank-ordered using the median of evaluator categorizations and
      the frequency of ratings per assigned relative performance quintile. Across
      evaluator groups and study years, the summary evaluation data consistently
      distinguished the top and bottom resident cohorts. DISCUSSION: An Internet-based
      instrument, using a single-item global ranking, demonstrated feasibility and can
      be used to differentiate top- and bottom-performing cohorts. Although ranking
      individuals yields norm-referenced measures of ability, successfully identifying
      poorly performing residents using online technologies is efficient and will be
      useful in developing and administering targeted evaluation and remediation
      programs.

PMID- 22379526
TI  - A multidisciplinary approach for teaching systems-based practice to internal
      medicine residents.
AB  - BACKGROUND: Rapid growth in the complexity of the health care environment
      (including monitoring systems for health care quality and patient safety) may
      result in graduating internists not being adequately prepared for the demands the
      system places on them. In response, the Residency Review Committee for Internal
      Medicine created the Educational Innovations Project (EIP) to encourage select
      residency training programs to develop new strategies and methods to meet
      changing demands in graduate medical education. METHODS: As part of the EIP, our
      program created an innovative administrative internship. This multiyear
      curriculum provides systems-based practice training and consists of a series of
      rotations that take place during the 3 years of internal medicine residency. Each
      session involves close interaction with the nonphysician personnel who are
      instrumental in making our institution a functional and cohesive unit. To assess
      the potential impact of the rotations, we survey senior residents, recent
      graduates, and faculty educators. In conjunction with the Performance and Patient
      Experience departments of the hospital, we track several systems-based practice
      metrics for residents, including compliance with core health care measures,
      length of stay, and patient satisfaction. RESULTS: Residents recognize the need
      to develop systems-based practice skills, to readily participate in structured
      curricula designed to enhance such skills, and to provide leadership in
      organizing and publishing quality improvement initiatives, and upon graduation,
      they may lament that they did not receive even more vigorous training in these
      areas. CONCLUSION: Although internal medicine residencies continue to improve
      their training in systems-based practice, our experience suggests that an even
      greater emphasis on these skills may be warranted.

PMID- 22379527
TI  - Pediatric intensive care simulation course: a new paradigm in teaching.
AB  - OBJECTIVE: True pediatric emergencies are rare. Because resident work hours are
      restricted and national attention turns toward patient safety, teaching methods
      to improve physician performance and patient care are vital. We hypothesize that
      a critical-care simulation course will improve resident confidence and
      performance in critical-care situations. INTERVENTIONS: We developed a monthly
      pediatric intensive care unit simulation course for second-year pediatric
      residents that consisted of weekly 1-hour sessions during both of the residents'
      month-long pediatric intensive care unit rotations. All scenarios used high
      fidelity pediatric simulators and immediate videotape-assisted debriefing
      sessions. In addition, simulated intraosseous line insertion and endotracheal
      intubations were also performed. RESULTS: All residents improved their comfort
      level and confidence in performing individual key resuscitation tasks. The
      largest improvements were seen with their perceived ability to intubate children
      and place intraosseous lines. Both of these skills improved from baseline and
      compared to third-year-resident controls who had pediatric intensive care unit
      rotations but no simulations (P = .05 and P = .07, respectively). Videotape
      reviews showed only 54% +/- 12% of skills from a scenario checklist performed
      correctly. CONCLUSIONS: Our simulation-based pediatric intensive care unit
      training course improves second-year pediatric residents' comfort level but not
      performance during codes, as well as their perceived intubation and intraosseous
      ability. Videotape reviews show discordance between objective performance and
      self-assessment. Further work is necessary to elucidate the reasons for this
      difference as well as the appropriate role for simulation in the new graduate
      medical education climate, and to create new teaching modalities to improve
      resident performance.

PMID- 22379528
TI  - A multirater instrument for the assessment of simulated pediatric crises.
AB  - BACKGROUND: Few validated instruments exist to measure pediatric code team
      skills. The goal of this study was to develop an instrument for the assessment of
      resuscitation competency and self-appraisal using multirater and gap analysis
      methodologies. METHODS: Multirater assessment with gap analysis is a robust
      methodology that enables the measurement of self-appraisal as well as competency,
      offering faculty the ability to provide enhanced feedback. The Team Performance
      during Simulated Crises Instrument (TPDSCI) was grounded in the Accreditation
      Council for Graduate Medical Education competencies. The instrument contains 5
      competencies, each assessed by a series of descriptive rubrics. It was piloted
      during a series of simulation-based interdisciplinary pediatric crisis resource
      management education sessions. Course faculty assessed participants, who also did
      self-assessments. Internal consistency and interrater reliability were analyzed
      using Cronbach alpha and intraclass correlation (ICC) statistics. Gap analysis
      results were examined descriptively. RESULTS: Cronbach alpha for the instrument
      was between 0.72 and 0.69. The overall ICC was 0.82. ICC values for the medical
      knowledge, clinical skills, communication skills, and systems-based practice were
      between 0.87 and 0.72. The ICC for the professionalism domain was 0.22. Further
      examination of the professionalism competency revealed a positive skew, 43
      simulated sessions (98%) had significant gaps for at least one of the
      competencies, 38 sessions (86%) had gaps indicating self-overappraisal, and 15
      sessions (34%) had gaps indicating self-underappraisal. CONCLUSIONS: The TPDSCI
      possesses good measures of internal consistency and interrater reliability with
      respect to medical knowledge, clinical skills, communication skills, systems
      based practice, and overall competence in the context of simulated
      interdisciplinary pediatric medical crises. Professionalism remains difficult to
      assess. These results provide an encouraging first step toward instrument
      validation. Gap analysis reveals disparities between faculty and self-assessments
      that indicate inadequate participant self-reflection. Identifying self
      overappraisal can facilitate focused interventions.

PMID- 22379529
TI  - Initial experiences in embedding core competency education in entry-level surgery
      residents through a nonclinical rotation.
AB  - BACKGROUND: Health care continues to expand in scope and in complexity. In this
      changing environment, residents are challenged with understanding its intricacies
      and the impact it will have on their professional activities and careers. AIM:
      Embedding each of the competency elements in residents in a meaningful way
      remains a challenge for many surgery residency program directors. METHODS: We
      established a nonclinical rotation to provide surgery postgraduate year-1 (PGY-1)
      residents with a structured, multifaceted, largely self-directed curriculum into
      which each of the 6 core competencies are woven. Posttesting strategies were
      established for most curricular experiences to ensure to the greatest possible
      extent that each resident will have achieved an acceptable level of understanding
      of each of the competency areas before being given credit for the rotation.
      RESULTS: By uniformly exceeding satisfactory scores on respective objective
      analyses, residents demonstrated an increased (at least short-term) understanding
      of each of the assessed competency areas. CONCLUSION: Our project sought to
      address a prior lack of opportunity for our residents to develop a sound
      foundation for our residents in systems-based practice. Our new rotation
      addresses systems-based practice in several different learning environments,
      including emergency medical service ride-along, sentinel event participation, and
      hospice visits. Several research projects have enhanced the overall learning
      program. Our experience shows that a rotation dedicated to competency training
      can provide an innovative and engaging means of teaching residents the value of
      each element.

PMID- 22379530
TI  - Morbidity and mortality conference in obstetrics and gynecology: a tool for
      addressing the 6 core competencies.
AB  - BACKGROUND: Residency program directors are challenged to effectively teach and
      assess the Accreditation Council for Graduate Medical Education's (ACGME) 6
      competencies. The purpose of this study was to characterize the morbidity and
      mortality (M&M) conference as a cost-effective and efficient approach for
      addressing the ACGME competencies through evaluation of resident participation
      and case diversity. METHODS: In our modified M&M conference, senior residents
      submit a weekly list of cases to the conference proctors. The resident presents
      the case, including a critique of management, using the medical literature. The
      resident submits a case summary evaluating patient care practices, integrating
      scientific evidence, and evaluating systemic barriers to care. Completed case
      summaries are distributed and archived for reference. RESULTS: During a 3-year
      period, 30 residents presented 196 cases. Of these, 37 (19%) directly related to
      systems-based practice, 20 (10%) involved problems with inadequate communication,
      and 11 (6%) included issues of professionalism or ethics. All cases involved
      practice-based learning and medical knowledge. CONCLUSIONS: The M&M conference
      addresses the core competencies through resident participation as well as
      directed analysis of diverse cases.

PMID- 22379532
TI  - Confessions of a superhero junkie.

PMID- 22379531
TI  - The surgical learning and instructional portfolio: what residents at a single
      institution are learning.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      Learning Portfolio is recommended as a tool to develop and document reflective,
      practice-based learning and improvement. There is no consensus regarding the
      appropriate content of a learning portfolio in medical education. Studying
      lessons selected for inclusion in their learning portfolios by surgical trainees
      could help identify useful subject matter for this purpose. METHODS: Each month,
      all residents in our surgery residency program submit entries into their
      individual Surgical Learning and Instructional Portfolio (SLIP). The SLIP entries
      from July 2008 to 2009 (n = 420) were deidentified and randomized using a random
      number generator. We conducted a thematic content analysis of 50 random portfolio
      entries to identify lessons learned. Two independent raters analyzed the "3
      lessons learned" portion of the portfolio entries and identified themes and
      subthemes using the constant comparative method used in grounded theory. RESULTS:
      The collaborative coding process resulted in theme saturation after the
      identification of 7 themes and their subthemes. Themes in decreasing order of
      frequency included complications, disease epidemiology, disease presentation,
      surgical management of disease, medical management of disease, operative
      techniques, and pathophysiology. Junior residents chose to focus on a broad array
      of foundational topics including disease presentation, epidemiology, and overall
      management of diseases, whereas postgraduate year-4 (PGY-4) and PGY-5 residents
      most frequently chose to focus on complications as learning points. CONCLUSIONS:
      Lessons learned reflect perceived needs of the trainees based on training year.
      When given a template to follow, junior and senior residents choose to reflect on
      different subject matter to meet their learning goals.

PMID- 22379533
TI  - The Impact of ACGME Work-Hour Reforms on the Operative Experience of Fellows in
      Surgical Subspecialty Programs.
AB  - BACKGROUND: In July 2003, the Accreditation Council for Graduate Medical
      Education (ACGME) introduced a set of regulations that mandated a reduction in
      the number of hours that medical residents can work. These requirements have
      generated controversy among medical educators, with some expressing concern that
      reducing resident hours may limit clinical exposure and competency, particularly
      in surgical specialties. OBJECTIVE: This study examines the impact of duty hour
      restrictions on resident operative experience in residents in 2 surgical
      subspecialties since the implementation of the ACGME duty hour limits. METHOD: We
      examined operative log data for vascular surgery and pediatric surgery, using the
      academic year immediately preceding the duty hour restrictions, 2002 to 2003, as
      a baseline for comparison to subsequent academic years through 2006 to 2007 for
      vascular surgery and 2007 to 2008 for pediatric surgery. RESULTS: Graduating
      fellows in pediatric surgery showed no change in their total operative volume
      following duty hour restrictions. The pediatric-defined category of neonate
      procedures showed an increase following duty hour restrictions. Graduating
      fellows in vascular surgery showed an increase in total major procedures as
      surgeon. The vascular-defined categories of endovascular-diagnostic, endovascular
      therapeutic, and endovascular-graft procedures also increased. CONCLUSIONS: The
      reduction of duty hours has not resulted in a decrease in operative volume as
      some have predicted. Operative volume in pediatric surgery remained mainly
      unchanged, whereas operative volume in vascular surgery increased. We explore
      possible explanations for the observed findings.

PMID- 22379534
TI  - Predictors of re-hospitalization in patients with chronic heart failure.
AB  - Heart failure (HF) is a chronic, progressive illness that is highly prevalent in
      the United States and worldwide. This morbid illness carries a very poor
      prognosis, and leads to frequent hospitalizations. Repeat hospitalization in HF
      is both largely burdensome to the patient and the healthcare system, as it is one
      of the most costly medical diagnoses among Medicare recipients. For years,
      investigators have strived to determine methods to reduce hospitalization rates
      of HF patients. Despite such efforts, recent reports indicate that re
      hospitalization rates remain persistently high, without any improvement over the
      past several years and thus, this topic clearly needs aggressive attention. We
      performed a key-word search of the literature for relevant citations. Published
      articles, limited to English abstracts indexed primarily in the PubMed database
      through the year 2011, were reviewed. This article discusses various clinical
      parameters, serum biomarkers, hemodynamic parameters, and psychosocial factors
      that have been reviewed in the literature as predictors of re-hospitalization of
      HF patients. With this information, our hope is that the future holds better risk
      stratification models that will allow providers to identify high-risk patients,
      and better customize effective interventions according to the needs of each
      individual HF patient.

PMID- 22379535
TI  - Abdominal aortic aneurysm screening during transthoracic echocardiography:
      Cardiologist and vascular medicine specialist interpretation.
AB  - AIM: To study the interobserver variability between a cardiologist and vascular
      medicine specialist in the screening of the abdominal aorta during transthoracic
      echocardiography (TTE). METHODS: Consecutive patients, > 55 years of age,
      underwent abdominal aortic imaging following standard TTE. Two cardiologists and
      one vascular medicine specialist performed a blinded review of the images.
      Interobserver agreement of abdominal aortic size was determined by the
      correlation coefficient and paired t test. Interobserver reliability for each
      cardiologist was assessed using Bland-Altman plots. RESULTS: Ninety patients were
      studied. The mean age of patients was 72 +/- 10 years and 48% were male. The mean
      aortic diameter was 2.31 +/- 0.50 cm and 5 patients (5.5%) had an abdominal
      aortic aneurysm (AAA). The additional time required for the abdominal aortic
      images was 4.4 +/- 0.9 min per patient. Interobserver agreement between the 2
      cardiologist interpreters and the vascular medicine specialist was excellent (P >
      0.05 for all comparisons). On Bland-Altman analysis of interobserver reliability,
      the 95% lower and upper limits for measurement by the cardiologists were 84% and
      124% of that of the vascular specialist. CONCLUSION: The assessment of the
      abdominal aorta during a routine TTE performed by a cardiologist is accurate in
      comparison to that of a vascular medicine specialist. In selected patients
      undergoing TTE, the detection rate of AAA is significant. Additional time and
      effort required to perform imaging of the abdominal aorta after TTE is less than
      5 min.

PMID- 22379536
TI  - Gender gap in acute coronary heart disease: Myth or reality?
AB  - AIM: To investigate potential gender differences in the prevalence of
      cardiovascular risk factors, cardiovascular disease (CVD) management, and
      prognosis in acute coronary syndrome (ACS). METHODS: A systematic literature
      search was performed through Medline using pre-specified keywords. An additional
      search was performed, focusing specifically on randomized controlled clinical
      trials in relation to therapeutic intervention and prognosis. In total, 92
      relevant articles were found. RESULTS: Women with CVD tended to have more
      hypertension and diabetes at the time of presentation, whereas men were more
      likely to smoke. Coronary angiography and revascularization by percutaneous
      coronary intervention were performed more often in men. Women were at a greater
      risk of short-term mortality and complications after revascularization.
      Interestingly, women under 40 years presenting with ACS were at highest risk of
      cardiovascular death compared with men of the same age, irrespective of risk
      factors. This disadvantage disappeared in older age. The long-term mortality risk
      of ACS was similar in men and women, and even in favor of women. CONCLUSION:
      Mortality rates are higher among young women with ACS, but this difference tends
      to disappear with age, and long-term prognosis is even better among older women.

PMID- 22379538
TI  - Evolution of ENT services in Oman.

PMID- 22379537
TI  - Percutaneous panvascular intervention in an unusual case of extensive
      atherosclerotic disease.
AB  - It is common to see patients with atherosclerotic coronary disease and peripheral
      arterial disease in routine clinical practice. One needs to have a comprehensive
      and integrated multi-speciality approach and panvascular revascularization in
      such patients. We report a 54-year-old diabetic hypertensive male with extensive
      atherosclerotic coronary and peripheral arterial disease, who presented with
      congestive heart failure, claudication of both lower limbs and mesenteric
      ischemia. He underwent successful percutaneous panvascular revascularization of
      coronary, renal, mesenteric, aorto-iliac and superficial femoral arteries. Long
      term patency of all the stents was also documented.

PMID- 22379539
TI  - How to prepare a Research Proposal.
AB  - Health research, medical education and clinical practice form the three pillars
      of modern day medical practice. As one authority rightly put it: 'Health research
      is not a luxury, but an essential need that no nation can afford to ignore'.
      Health research can and should be pursued by a broad range of people. Even if
      they do not conduct research themselves, they need to grasp the principles of the
      scientific method to understand the value and limitations of science and to be
      able to assess and evaluate results of research before applying them. This review
      paper aims to highlight the essential concepts to the students and beginning
      researchers and sensitize and motivate the readers to access the vast literature
      available on research methodologies.

PMID- 22379540
TI  - Idiopathic Intracranial Hypertension (IIH).
AB  - The first report of Idiopathic Intracranial Hypertension (IIH) was by Quinche in
      1893. Throughout history it has had many names. When I was a child growing up,
      before we had antibiotic therapy, middle ear infections occasionally would
      trigger intracranial inflammation and the disease was called Otitic
      Hydrocephalus. Then it was called Benign Intracranial Hypertension which we now
      know is far from benign. In 1931 Symonds was the first to suggest that it was
      caused by dural sinus obstruction. Loss of vision or field is not uncommon in
      untreated cases. We now use the term Idiopathic Intracranial Hypertension to
      express our ignorance about the cause and mechanism of the disease. Some cases
      are related to causes that we can identify and correct. These include Vitamin A,
      Tetrcycline, Lithium and Corticosteroids. The mechanism of these are not fully
      understood but their causal relationship is historically known. Many cases still
      fall into the unknown cause category.

PMID- 22379541
TI  - Lactational Amenorrhoea and Modern Contraceptives Use among Nursing Women in
      Egypt 2003.
AB  - OBJECTIVES: To evaluate the potential for Lactational Amenorrhoea Method (LAM)
      and passive LAM among women with children below 6 months in the 2003 Egypt
      Demographic Health Survey (2003 EDHS), to assess the determinants of amenorrhea,
      and to examine the association of exclusive breastfeeding and amenorrhea with
      using modern contraceptive methods among nursing mothers of children below 2
      years, adjusting for other associated variables. METHODS: Data from the 2003 EDHS
      was downloaded from the DHS website. A sub-sample of women fulfilling all the
      four criteria were selected: 1) women with last birth of children less than 2
      years; 2) currently married; 3) not being sterilized; and 4) currently breast
      feeding their children. Accordingly, 1934 women entered into the statistical
      analysis, of them 629 had children below 6 months. RESULTS: Nearly 24% of nursing
      mothers with children below 6 months met LAM criteria, of them passive LAM users
      constituted 79.1%. For women with children below 24 months, determinants of
      amenorrhea were exclusive breast feeding, unemployment, number of living
      children, husband education, number of feeding at night, and having a male sex
      child. Higher education, urban residence, positive attitude towards contraception
      increased the likelihood of modern contraceptives use, whereas amenorrhea,
      exclusive breast feeding, and having a wanted child decreased its likelihood in
      multivariate analysis. CONCLUSION: Exclusive breast feeding was associated with
      amenorrhea and modern contraceptive methods use in a direct and inverse fashion
      respectively. LAM is a commonly used method but it is liable to discontinuation
      or violation of its criteria. Hence, it is recommended to educate both the health
      care providers and users about it.

PMID- 22379542
TI  - Antibiotic combination as empirical therapy for extended spectrum Beta-lactamase.
AB  - BACKGROUND: extended spectrum beta-lactamase (ESBL) producing gram negative
      bacilli are becoming a growing problem worldwide with difficulties in designing a
      national formulary for empirical treatment of gram negative sepsis. OBJECTIVES:
      In this study, we investigated the in vitro activity of Carbapenems, Pipracillin
      Tazobactam, Ciprofloxacin alone or in combination with aminoglycosides against
      ESBL-producing strains isolated from clinical samples. METHODS: Three hundred and
      one ESBL-producing Escherichia coli and K. pneumoniae strains isolated from
      clinical samples were investigated. Isolates were screened initially for ESBL
      production using an automated system. All ESBL isolates were further confirmed
      using the double-disk diffusion method. RESULTS: The overall Piperacillin
      Tazobactam susceptibility was 57.9 (64.4% E. coli and 43.6% Klebsiella
      pneumoniae). Only 29.6% of ESBLs (24.9% E. coli and 39.6% Klebsiella pneumoniae)
      were ciprofloxacin susceptible. 98.1% E. coli and 93.1% of Klebsiella pneumoniae
      were susceptible to Piperacillin-Tazobactam plus Amikacin combination. 73.7% E.
      coli and 61.4% of Klebsiella pneumoniae were susceptible to Piperacillin
      Tazobactam plus Gentamicin combination. 96.7% E. coli and 91.1% of Klebsiella
      pneumoniae were susceptible to Ciprofloxacin plus Amikacin combination. 41.2% E.
      coli and 51.5% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus
      Gentamicin combination. CONCLUSION: ESBLs have high resistance profile against
      Piperacillin/Tazobactam and Ciprofloxacin. The ESBLs from Oman have similar
      resistantce pattern as those reported from UK and USA. This resistance decreases
      when these drugs are combined with Amikacin. All ESBLs are susceptible to
      Carbapenems. However, carbepenam overuse can lead to emergence of carbapenems
      resistant gram negative bacilli and ESBLs. Combination of Amikacin plus
      Piperacillin/Tazobactam is a feasible empirical therapy for ESBLs.

PMID- 22379543
TI  - Outcome of trabeculectomy surgery in primary open angle glaucoma.
AB  - OBJECTIVES: Retrospective study to evaluate the short term outcome and
      contributing prognostic factors of trabeculectomy in terms of intraocular
      pressure in Omani patients of South Batinah region with primary open-angle
      glaucoma. METHODS: This study involved retrospective evaluation of 18 patients
      (22 eyes) with primary open angle glaucoma who underwent primary trabeculectomy
      between February 2005 and February 2008. All patients were aged over 40 years and
      were Omani. Follow-up for all subjects lasted at least 6 months or more [Average
      follow up 388 days with standard deviation of 182]. Successful control of
      Intraocular pressure (IOP) was defined as achieving IOP of 21 mmHg or less
      without medication (complete success). RESULTS: The results are presented with
      particular emphasis being placed only on intraocular pressure (IOP) control. The
      tonometric success rate of trabeculectomy in controlling the IOP at 21mmHg or
      less without any medication was 46% [complete successes], 18% had qualified
      success [Post operative IOP 21 mm Hg or less with one topical medication], while
      36% trabeculectomies failed to show desired results. CONCLUSION: The results of
      this retrospective study underline that the procedure of trabeculectomy has
      moderate success in controlling the intra ocular pressure in the study
      population. The procedure failed to show the desired result in almost one third
      of the patients (36%) and topical medical treatment was reinstated in these
      patients with either two or three drugs. However these results lead to the
      following question: Should trabeculectomy be the therapy of first choice in the
      early stage of glaucoma?

PMID- 22379544
TI  - Asthma Knowledge among Asthmatic School Students.
AB  - OBJECTIVES: Bronchial asthma is a common and life threatening problem affecting
      school children and adolescents. The flare-up of asthma may lead to impaired
      daily function and absence from school. These complications of bronchial asthma
      could be influenced by poor knowledge, poor use of inhaler technique, non
      compliance and negative attitude toward the illness and drugs. The study is
      designed to assess the asthma knowledge of school students suffering form asthma
      and identify the resources of the knowledge. METHODS: All diagnosed asthma
      students (131 cases) selected from school health register grade 7-12 was included
      in this study. The self administrated questionnaire was distributed among them.
      It was designed to collect information of the students about epidemiology of
      asthma, source of their information and effect of the disease on their school
      attendance. Special knowledge score was constructed to measure the level of the
      students' knowledge. RESULTS: The study showed that from 131 diagnosed asthma
      cases 90% (118) aware about their diagnosis. Medical and paramedical personnel
      were found to be the source of knowledge for 49.4% (65) of the students, while
      teachers were mentioned by only 9.2% (12) of the students as their source of
      information. Regarding the effect of asthma on school absenteeism, 66% (87) of
      school students may miss their school due asthma attack. CONCLUSION: Health
      education about bronchial asthma is a need for school students. This require
      inter-disciplinary approach from various organization particularly the schools.
      It is vital that school teachers' knowledge be improved and continuously updated
      that it can reflect in students' knowledge and attitudes too.

PMID- 22379545
TI  - Use of ventilator bundle to prevent ventilator associated pneumonia.
AB  - OBJECTIVES: To determine if the knowledge and awareness of "ventilator bundle"
      helped in the prevention of ventilator associated pneumonia and other outcome
      variables in the patients admitted to our AICU. DESIGN: A retrospective
      obsevational study from a pospectively collected data. PARTICIPANTS: All the
      adult medical and surgical patients who were intubated and ventilated in our AICU
      from January to September in the year 2005 and 2006 were included in the study.
      During the period of October to December 2005 the critical care nurses and the
      staff were educated and made aware about the problem of VAP and the use of
      vrntilator bundle in helping to prevent this nososcomial infection. Patients who
      expired within 24 hrs of admission, who were transferred to tertiary care unit
      within 48hrs, and those who were diagnosed with pulmonary embolism or had
      gastrointestinal bleed prior to admission were excluded from this study.
      INTERVENTION: The concept of " ventilator bundle' was introduced after educating
      the nursing staff, respiratory therapists and the medical personnel through group
      discussions and presentations in the infection control and staff development
      symposia. "Ventilator bundle "is a package of evidence -based interventions that
      include: (1) Elevation of patient's head of bed to 30- 45 degrees; (2) Daily
      sedation vacation and daily assessment of readiness to extubation; (3) Peptic
      ulcer prophylaxis; (4) Deep vein thrombosis (DVT) prophylaxis. MEASUREMENT:
      Demographic data was collected from the computer database. VAP was diagnosed when
      it met the (clinical non-invasive) diagnostic criteria. Incidence of VAP was
      calculated in the medical and surgical patients separately. RESULTS: Introducing
      the concept of "ventilator bundle" significantly reduced the incidence of VAP by
      24.2% in the surgical patients and by 12% in the medical group. It significantly
      reduced the incidence of upper gastrointestinal bleed. The mean age of patients
      who developed VAP in 2006 was significantly higher in both the medical and the
      surgical groups. The length of stay decreased significantly in the surgical
      group, while it increased in the medical group. The mean duration of ventilation
      was reduced by 29.1% in the medical group and by 55.12% in the surgical group in
      those patients who developed VAP. In patients who did not develop VAP, the
      decrease of 9.9% in the mean duration of ventilation was seen in the surgical
      group while the mean duration of ventilation increased by 14.2% in the medical
      group. CONCLUSIONS: Introducing the concept of "ventilator bundle" helped us to
      reduce the incidence of VAP, reduce the incidence of upper gastrointestinal
      bleed. It reduced the mean duration of ventilation in both the medical and
      surgical patients who developed VAP. The effect on decreasing the length of stay
      was seen in the surgical patients only.

PMID- 22379546
TI  - Acute Renal Failure in a Patient with both Leptospirosis and Dengue Fever.
AB  - The spectrum of tropical nephropathies includes Acute Renal Failure (ARF) or
      Acute Kidney Injury (AKI) due to infective agents that are endemic in the tropics
      which include Leptospira (LS) and Dengue Viruses (DV). The major histological
      feature is Acute Tubular Necrosis (ATN).(1, 2)We report the case of a patient who
      presented ARF with co-infection with both agents. The clinical manifestations
      were consistent with both diseases. A renal treatment was supportive and the
      outcome was positive.We conclude that co-infection with these two tropical agents
      was possible. It may have been overlooked when the diagnosis of one agent was
      confirmed, especially that aware of the possibility of co-infection, as the
      management may be different. Spontaneous full recovery in these circumstances is
      still possible with supportive treatment.

PMID- 22379547
TI  - Paroxysmal supraventricular tachycardia in the rural setting- case reports and
      review.
AB  - A case report of three Omani children age ranging from one month to ten years
      managed in a district hospital. All three children reverted to normal sinus
      rhythm after I.V. adenosine and are under follow up. A detailed review of
      management of Paroxysmal Supraventricular Tachycardia is discussed. Treatment
      options include no treatment, vagal manoeuvres, long term drug therapy,
      radiofrequency catheter ablation, and surgery. Recurrence may occur and patients
      have to be educated about home management and when to seek medical help.

PMID- 22379548
TI  - Lipoid Pneumonia Following Aspiration of Ghee (animal fat) in an Omani Infant.
AB  - We are reporting, what we believe, is the first case of biopsy proven exogenous
      lipoid pneumonia in an Omani infant. Exogenous lipoid pneumonia is caused by
      aspiration of oily products .One reason is the traditional practice of giving
      infants oily products (Ghee) as in our patient.

PMID- 22379549
TI  - Acute cardiovascular emergency: missed killer in the emergency room.
AB  - Acute chest pain in hypertensive patients presenting to the emergency room
      constitute a wide spectrum of life threatening conditions including an acute
      aortic dissection. Acute Aortic syndromes constitute uncommon but lethal
      identities, with high morbidity and mortality requiring a high index of
      suspicion, appropriate diagnostic tools and urgent line of management. The
      authors are reporting a case of an elderly hypertensive lady, presenting with
      acute chest pain secondary to type B aortic dissection, which was missed on the
      initial presentation. The authors reviewed the current practice of diagnosing and
      managing acute aortic dissection.

PMID- 22379550
TI  - Chondroid lipoma: a case report.
AB  - Chondroid lipoma is a unique, uncommon benign lipomatous tumour. Due to distinct
      morphological simily, it is important to distinguish it from extraskeletal
      chondrosarcoma and myxoid/round cell liposarcoma (MRCLS). We report such a
      neoplasm with brief a review of literature.

PMID- 22379551
TI  - Multiple skin bullae.

PMID- 22379552
TI  - Thumb duplication: concepts and techniques.
AB  - Within the Oberg, Manske, Tonkin (OMT) classification, thumb duplications are a
      failure of formation and/or differentiation affecting the radial-ulnar axis of
      the hand plate. The Wassel description of seven types of thumb duplication
      provides a good structure from which an approach to management is based. The aim
      of surgical reconstruction is to obtain a stable, mobile thumb of adequate size
      and appropriate shape. The most common form of reconstruction is removal of the
      lesser digit and reconstruction of the dominant digit. Surgical techniques
      address the problems of deviation, instability and lack of size. The
      disadvantages of the Bilhaut-Cloquet procedure, these being joint stiffness and a
      nail ridge, may be lesser concerns when reconstruction of one digit will not
      create a satisfactory thumb of adequate mobility, stability, alignment and size.
      Complicated problems of triphalangism, triplication, ulnar dimelia and the rare
      circumstance in which neither of the duplicated thumbs may be adequately
      reconstructed present specific challenges which demand alternative techniques.

PMID- 22379553
TI  - Pollicization: the concept, technical details, and outcome.
AB  - Pollicization substitutes a functioning finger for a deficient thumb. The most
      indication is thumb hypoplasia with absence or instability of the carpometacarpal
      joint. However, there are additional causes that may negate thumb function, such
      as trauma, macrodactyly, multi-fingered hand, and a mirror hand. The technique of
      pollicization represents a consolidation of contributions from surgeons over the
      last 100 years. A meticulous stepwise approach from incision to closure is
      necessary to optimize outcome. Following pollicization, cortical plasticity and
      motor relearning play a pivotal role in function following pollicization with
      connections and adjacent sprouting from nearby cortical and/or subcortical
      territories. Occupational therapy is necessary to encourage large object
      acquisition followed by smaller objects and ultimately fine pinch. Pollicization
      is more reliable in patients with isolated thumb hypoplasia and a mobile index
      finger with robust extrinsic and intrinsic muscle-tendon units compared to and
      patients with radial forearm deficiencies and diminished index mobility.

PMID- 22379554
TI  - Changing paradigms in the treatment of radial club hand: microvascular joint
      transfer for correction of radial deviation and preservation of long-term growth.
AB  - Radial longitudinal deficiency, also known as radial club hand, is a congenital
      deformity of the upper extremity which can present with a spectrum of upper limb
      deficiencies. The typical hand and forearm deformity in such cases consists of
      significant forearm shortening, radial deviation of the wrist and hypoplasia or
      absence of a thumb. Treatment goals focus on the creation of stable centralized
      and functionally hand, maintenance of a mobile and stable wrist and preservation
      of longitudinal forearm growth. Historically centralization procedures have been
      the most common treatment method for this condition; unfortunately centralization
      procedures are associated with a high recurrence rate and have the potential for
      injury to the distal ulnar physis resulting in a further decrease in forearm
      growth. Here we advocate for the use of a vascularized second metatarsophalangeal
      joint transfer for stabilization of the carpus and prevention of recurrent radial
      deformity and subluxation of the wrist. This technique was originally described
      by the senior author in 1992 and he has subsequently been performed in 24 cases
      with an average of 11-year follow-up. In this paper we present an overview of the
      technique and review the expected outcomes for this method of treatment of radial
      longitudinal deficiency.

PMID- 22379555
TI  - Free fat graft for congenital hand differences.
AB  - BACKGROUND: Free fat graft has been used for the treatment of congenital hand
      differences. However, there have been a few reports about the outcome of that
      treatment. In this study, the outcome of free fat grafts for congenital hand and
      foot differences was investigated. METHODS: Fourteen bones with longitudinal
      epiphyseal bracket, 3 wrists with Madelung deformity, and 5 cases of osseous
      syndactyly were treated with free fat graft with osteotomy, physiolysis, or
      separation of osseous syndactyly. Of the fourteen bones with longitudinal
      epiphyseal bracket, 9 were treated with open wedge osteotomy with free fat graft
      and 5 with physiolysis and free fat graft. The Madelung deformity was treated
      with physiolysis with free fat graft. For osseous syndactyly, syndactyly release
      with free fat graft was performed five times on four hands. RESULTS: In the
      fourteen cases with longitudinal epiphyseal bracket, lateral deviation improved
      in all except two cases after surgery. The average lateral deviation angle
      changed from 32.5 degrees before surgery to 15.2 degrees after surgery. The
      average improvement of the lateral deviation angle was 12.2 degrees in the
      osteotomy group and 20.6 degrees in the physiolysis group. The mean ratio of
      improvement of the lateral deviation angle to the lateral deviation angle before
      surgery was 39.4% in the osteotomy group and 51.2% in the physiolysis group. The
      Madelung deformity improved after surgery in two cases but there was no
      improvement in one case. For these conditions, the results were not good enough
      when surgery was done after age 13 or at age four for severely hypoplastic
      brachymesophalangy. Of the 5 cases of osseous syndactyly, reunion of the
      separated bones occurred in one case. The grafted free fat should be deep enough
      to cover the osteotomy site of the bones to prevent reunion of the separated
      bones. CONCLUSIONS: Physiolysis and free fat graft performed during the growth
      period can correct the deviation due to longitudinal epiphyseal bracket and
      Madelung deformity. Free fat graft is also useful to prevent reunion of the bones
      after separation of osseous syndcatyly, if the grafted fat is securely filled
      into the space between the separated bones.

PMID- 22379556
TI  - Classification and surgical treatment of symphalangism in interphalangeal joints
      of the hand.
AB  - BACKGROUND: Symphalangism is a rare congenital difference characterized by
      ankylosis of interphalangeal (IP) joints of the fingers and toes. In adults,
      there were several attempts to restore the stiff joints into mobile ones, but
      these treatment options resulted in poor outcomes and could not be applied to
      growing children. Here, we report our experiences on surgical treatment for
      children who had symphalangism of the hand. METHODS: We treated 36 joints in 17
      children with symphalangism of the hand using dorsal capsulotomy and collateral
      ligament release. The diagnoses were based on history, physical examination, and
      simple radiographs. Affected fingers were classified according to our grading
      system. Simple compressive dressing was applied using Coban after surgery.
      Passive range of motion (ROM) exercise was started on day one or 2 postoperative,
      with the help of a hand therapist and patients' parents. The patients were
      prescribed passive ROM exercises for at least 2 hours a day over a period of 6
      months. RESULTS: A single surgeon operated on 30 proximal IP joints, 3 distal IP
      joints, and 3 IP joints of the thumb. Twenty six joints were classified as grade
      I, and 10 as grade II. The ROM of affected joints, which was 7.8 +/- 8.1 (mean +/
      SD) degrees preoperatively, increased to 46.8 +/- 18.6 degrees at final follow
      up. The final ROM was significantly better in grade I joints, especially when the
      children had operations at ages 24 months or younger. CONCLUSIONS: Symphalangism
      of the hand in children, can be restored into a mobile joint by release of the
      collateral ligament, a dorsal capsulotomy, and postoperative physical therapy.

PMID- 22379557
TI  - Progression of a fracture site impaction as a prognostic indicator of impacted
      femoral neck fracture treated with multiple pinning.
AB  - BACKGROUND: We evaluated the clinical and radiologic results of impacted femoral
      neck fractures treated with multiple pinning and determined the influence of the
      progression of impaction at the fracture site on clinical outcome. METHODS: There
      were 34 patients with a mean age of 65.5 years. The mean follow-up period was 3.4
      years. Progression of fracture site impaction was measured using an articulo
      trochanteric distance index and the percentage decrease in the articulo
      trochanteric distance index between follow-up intervals. The failure of treatment
      was clarified as non-union and avascular necrosis. Other characteristics of the
      patients, including mean waiting time for surgery, preoperative Singh index
      score, and body mass index, were also measured to evaluate the influence on the
      clinical outcome of surgery. RESULTS: There were 6 fractures which were not
      treated successfully (3 non-union, 8.8% and 3 avascular necrosis, 8.8%). The mean
      percentage decrease of the articulo-trochanteric distance index within the first
      6 weeks after surgery was 4.5% in the successful group and 25.1% in the failure
      group (p < 0.001). There was also a significant mean percentage decrease in the
      articulo-trochanteric distance index between 6 weeks and 3 months (p < 0.001).
      CONCLUSIONS: Primary stabilization with Knowles pins for impacted femoral neck
      fractures had a reasonable clinical outcome with low morbidity. Despite a
      significant difference of a mean percentage decrease in the articulo-trochanteric
      distance index between the successful group and the failure group, we could not
      verify it as a risk factor for failure of treatment because the odds ratio was
      not statistically significant.

PMID- 22379558
TI  - Anatomic reduction of mallet fractures using extension block and additional
      intrafocal pinning techniques.
AB  - BACKGROUND: The purpose of this article is to report the efficacy of the
      extension block pinning and additional intrafocal pinning technique applied to
      cases whose mallet fractures were not reduced with extension block pinning alone.
      METHODS: We retrospectively reviewed 14 digits with 14 patients who were treated
      with the extension block pinning and additional intrafocal pinning technique.
      There were eight men and six women with an average age of 34 years. The average
      articular surface involvement was 52%. The average follow-up was 16 months and
      the mean time from injury to operation was 23 days. RESULTS: All the cases
      achieved anatomic reduction of fractures. By Crawford's classification, 9 were
      excellent and 5 were good. The average active flexion of the distal
      interphalangeal joint was 78 degrees and the average extension loss was 1.8
      degrees. Bone union was observed in all cases after a postoperative mean of 38.4
      days. Complications such as skin necrosis, fracture of bony fragments, and nail
      plate deformity were not found. CONCLUSIONS: Additional intrafocal pinning
      technique is considered a simple and useful method to obtain anatomic reduction
      of mallet fractures in cases where extension block pinning alone is insufficient
      to restore the anatomic configuration of the articular surface.

PMID- 22379559
TI  - Efficacy of postoperative radiograph for evaluating the prevertebral soft tissue
      swelling after anterior cervical discectomy and fusion.
AB  - BACKGROUND: After surgery for degenerative spinal disease by the anterior
      approach, the degree of soft tissue swelling can be assessed simply using plain
      radiographs. However, there are little studies according to the surgical methods
      or extent of surgery, and no study had addressed the clinical meaning of swelling
      determined by plain radiography. The purpose of this study was to evaluate the
      clinical significance of prevertebral soft tissue swelling (PSTS) after anterior
      cervical fusion with plate fixation for the treatment of degenerative cervical
      spinal disorders. METHODS: One hundred and thirty-five patients that underwent
      anterior cervical fusion with plate augmentation for degenerative cervical
      spondylosis were included in this study. PSTS differences were analyzed with
      respect to numbers of fusion segments and location of fusion. Cases were divided
      into two groups based on the amount of PSTS, and incidences of dyspnea,
      dysphagia, dysphonia were evaluated. RESULTS: PSTS increments were significantly
      greater in patients that had undergone multi-level or high-level fusion.
      Complications of dyspnea, dysphagia and dysphonia were found more frequently in
      patients with marked PSTS group. CONCLUSIONS: Increments of PSTS after anterior
      cervical fusion for degenerative spinal disorders are greater and incidences of
      complications are higher in patients that undergo multi-level or high-level
      fusion. Thus, measurement of PSTS using consecutive cervical lateral radiographs
      after anterior cervical surgery is clinically meaningful procedure.

PMID- 22379560
TI  - Evaluation of the sigmoid notch involvement in the intra-articular distal radius
      fractures: the efficacy of computed tomography compared with plain X-ray.
AB  - BACKGROUND: The purpose of this study is to evaluate the efficacy of computed
      tomography (CT) scans compared with plain radiographs on detecting the
      involvement of the sigmoid notch. METHODS: This study involved 121 cases
      diagnosed as the intra-articular distal radius fracture and performed post
      reduction CT scans. We determined the presence of the sigmoid notch involvement
      with both plain radiographs and CT scans and compared findings of plain
      radiographs with CT scans about the incidence and the pattern of injuries. And
      the differences of results between arbeitsgemeinschaft fur osteosyntheses (AO)
      type C2 and C3 were compared. RESULTS: The incidences of sigmoid notch
      involvement detected in plain radiographs were 81 cases (66.9%), whereas CT scans
      were 99 cases (81.9%). The sensitivity of plain radiographs compared with CT
      scans was 74.7%, the specificity was 68.2%, the positive predictive value was
      91.4%, the negative predictive value was 37.5%, the false negative value was
      25.3%, and the false positive value was 31.8%. In comparison between AO type C2
      and C3, the incidence of sigmoid notch involvement was not a significant
      difference, but the displacement of fracture fragment showed a significant
      difference. CONCLUSIONS: The intra-articular distal radius fracture usually
      accompanies the sigmoid notch involvement. Considering that the evaluation of
      sigmoid notch involvement by plain radiography often results in misinterpretation
      or underestimation, performing CT scan in intra-articular distal radius fracture
      is thought to be beneficial.

PMID- 22379561
TI  - Consensus and different perspectives on treatment of supracondylar fractures of
      the humerus in children.
AB  - BACKGROUND: Although closed reduction and percutaneous pinning is accepted as the
      treatment of choice for displaced supracondylar fracture of the humerus, there
      are some debates on the pinning techniques, period of immobilization, elbow range
      of motion (ROM) exercise, and perceptions on the restoration of elbow ROM. This
      study was to investigate the consensus and different perspectives on the
      treatment of supracondylar fractures of the humerus in children. METHODS: A
      questionnaire was designed for this study, which included the choice of pinning
      technique, methods of elbow motion, and perception on the restoration of elbow
      ROM. Seventy-six orthopedic surgeons agreed to participate in the study and
      survey was performed by a direct interview manner in the annual meetings of
      Korean Pediatric Orthopedic Association and Korean Society for Surgery of the
      Hand. There were 17 pediatric orthopedic surgeons, 48 hand surgeons, and 11
      general orthopedic surgeons. RESULTS: Ninety-six percent of the orthopedic
      surgeons agreed that closed reduction and percutaneous pinning was the treatment
      of choice for the displaced supracondylar fracture of the humerus in children.
      They showed significant difference in the choice of pin entry (lateral vs.
      crossed pinning, p = 0.017) between the three groups of orthopedic surgeons, but
      no significant difference was found in the number of pins, all favoring 2 pins
      over 3 pins. Most of the orthopedic surgeons used a removable splint during the
      ROM exercise period. Hand surgeons and general orthopedic surgeons tended to be
      more concerned about elbow stiffness after supracondylar fracture than pediatric
      orthopedic surgeons, and favored gentle passive ROM exercise as elbow motion.
      Pediatric orthopedic surgeons most frequently adopted active ROM exercise as the
      elbow motion method. Pediatric orthopedic surgeons and general orthopedic
      surgeons acknowledged that the patient's age was the most contributing factor to
      the restoration of elbow motion, whereas hand surgeons acknowledged the amount of
      injury to be the most contributing factor. CONCLUSIONS: More investigation and
      communication will be needed to reach a consensus in treating pediatric
      supracondylar fractures of the humerus between the different subspecialties of
      orthopedic surgeons, which can minimize malpractice and avoid medicolegal issues.

PMID- 22379562
TI  - Nodular fasciitis with cortical erosion of the hand.
AB  - Nodular fasciitis is a benign, reactive myofibroblastic tumor that is often
      mistaken for a sarcoma because of its histological appearance and rapid growth.
      Involvement of a finger is extremely rare. We report a case of nodular fasciitis
      of the thumb, accompanied by bone erosion. Magnetic resonance findings suggested
      the possibility of a malignancy, which could have led to misdiagnosis as a
      malignant soft tissue sarcoma. Instead, the lesion was treated by excisional
      biopsy, which confirmed nodular fasciitis. There has been no evidence of local
      recurrence at recent follow-up, 1 year after surgery. This case illustrates that,
      to avoid unnecessarily aggressive surgery, nodular fasciitis must be included in
      the differential diagnosis for any finger lesion that resembles a sarcoma, even
      if bone erosion is present.

PMID- 22379563
TI  - Insight into the effects of dexmedetomidine on intraoperative hemodynamics and
      postanesthetic recovery speed.

PMID- 22379564
TI  - The effect of dexmedetomidine on the adjuvant propofol requirement and
      intraoperative hemodynamics during remifentanil-based anesthesia.
AB  - BACKGROUND: The effects of dexmedetomidine on the propofol-sparing effect and
      intraoperative hemodynamics during remifentanil-based propofol-supplemented
      anesthesia have not been well investigated. METHODS: Twenty patients undergoing
      breast surgery were randomly allocated to receive dexmedetomidine (group DEX) or
      placebo (group C). In the DEX group, dexmedetomidine was loaded (1 ug/kg) before
      anesthesia induction and was infused (0.6 ug/kg/h) during surgery. Anesthesia was
      induced with a target-controlled infusion (TCI) of propofol (effect site
      concentration, Ce; 3 ug/ml) and remifentanil (plasma concentration, Cp, 10
      ng/ml). The Ce of TCI-propofol was adjusted to a bispectral index of 45-55, and
      Cp of TCI-remifentanil was fixed at 10 ng/ml in both groups. Mean arterial blood
      pressure (MAP) and heart rate (HR) were recorded at baseline (T-control), after
      the loading of study drugs (T-loading), 3 min after anesthesia induction (T
      induction), tracheal intubation (T-trachea), incision (T-incision), 30 min after
      incision (T-incision30), and at tracheal extubation (T-extubation). MAP% and HR%
      (MAP and HR vs. T-control) were determined and the propofol infusion rate was
      calculated. RESULTS: The propofol infusion rate was significantly lower in the
      DEX group than in group C (63.9 +/- 16.2 vs. 96.4 +/- 10.0 ug/kg/min,
      respectively; P < 0.001). The changes in MAP% at T-induction, T-trachea and T
      incision in group DEX (-10.0 +/- 3.9%, -9.4 +/- 4.6% and -11.2 +/- 6.3%,
      respectively) were significantly less than those in group C (-27.6 +/- 13.9%, 
      21.7 +/- 17.1%, and -25.1 +/- 14.1%; P < 0.05, respectively). CONCLUSIONS:
      Dexmedetomidine reduced the propofol requirement for remifentanil-based
      anesthesia while producing more stable intraoperative hemodynamics.

PMID- 22379565
TI  - Macintosh laryngoscope vs. Pentax-AWS video laryngoscope: comparison of efficacy
      and cardiovascular responses to tracheal intubation in major burn patients.
AB  - BACKGROUND: Patients with major burns accompanied with airway edema need more
      attention for airway management. Although the Pentax-AWS has an advantage in
      managing endotracheal intubation more easily, its usefulness cannot be assured if
      it does not maintain hemodynamic stability in burn patients. The aim of this
      study was to compare cardiovascular responses and general efficacy of the Pentax
      AWS and Macintosh laryngoscopes in burn patients. METHODS: American Society of
      Anesthesiologists physical status 2 or 3 adult patients with major burn injury
      were randomly assigned to group P (AWS, n = 50) or group M (Macintosh, n = 50).
      Fifty-nine patients assigned to the Macintosh group and no patient to AWS group
      were excluded because of failure to first intubation. Hemodynamic data at
      baseline, just before and after intubation as well as 3, 5 and 10 minutes after
      intubation and grade of sore throat were recorded in two groups. Intubation time,
      success rate of intubation, number of intubation attempts and the percentage of
      glottic opening (POGO) scores were also observed and analyzed in all patients.
      RESULTS: A statistically significant increase in heart rate just after
      laryngoscopy was seen in group M. The success rate of the first attempt in group
      P (100%) was greater than with the group M (46%). POGO scores were higher in
      group P (97 +/- 4%) than in group M (48 +/- 29%) CONCLUSIONS: The use of Pentax
      AWS offers a reduced degree of heart rate elevation compared with the Macintosh
      laryngoscope and better intubation environments in major burn patients.

PMID- 22379566
TI  - The effect of type of anesthesia on intra-and postoperative blood loss at
      elective cesarean section.
AB  - BACKGROUND: In cesarean section (c-sec) it is known that women receiving spinal
      anesthesia have decreased intraoperative blood loss compared to women receiving
      general anesthesia. However, we should always consider postoperative bleeding
      (postpartum bleeding) that may follow. The amount of postpartum bleeding can be
      substantial. Therefore, we sought to evaluate the effect of type of anesthesia
      retrospectively on intra- and postoperative blood loss by comparing the changes
      of postoperative Hb, Hct at c-sec. METHODS: We retrospectively compared the
      medical records of 287 elective c-sec patients. We excluded medical and obstetric
      conditions that may predispose such patients to increased blood loss. Subsequent
      detailed record analysis included 152 patients that received spinal anesthesia
      (group S), and 135 patients that received sevoflurane for general anesthesia
      (group G). RESULTS: In comparison with the preoperative Hb, rates of Hb in the
      1(st) postoperative day in group S significantly decreased compared to group G,
      but there was no significant difference in decreasing rates of Hb in the 3(rd)
      postoperative day between groups S and G. Estimated blood loss (EBL) of the
      intraoperative and operative day in group S was significantly lower compared to
      group G, but there was no significant difference in EBL of 1(st) and 2(nd)
      postoperative day between groups S and G. CONCLUSIONS: We conclude that group S
      had a decrease in blood loss between the intraoperative and operative day and
      there was no significant differences in postoperative blood loss compared with
      group G.

PMID- 22379567
TI  - Dexamathasone added to levobupivacaine improves postoperative analgesia in
      ultrasound guided interscalene brachial plexus blockade for arthroscopic shoulder
      surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of the addition
      of 5 mg dexamethasone to 10 ml of 0.5% levobupivacaine on postoperative analgesic
      effects of ultrasound guided-interscalene brachial plexus block (ISBPB) in
      arthroscopic shoulder surgery under general anesthesia. METHODS: In 60 patients
      scheduled for arthroscopic shoulder surgery that underwent general anesthesia,
      ISBPB was preoperatively performed with 10 ml of 0.5% levobupivacaine under the
      guidance of ultrasound and a nerve stimulator. Patients were randomly allocated
      to receive the same volume of normal saline (Group I), 5 mg of dexamethasone
      (Group II), or 1 : 400,000 epinephrine (Group III) as an adjuvant to the mixture.
      A blind observer recorded total analgesic consumption, sleep quality,
      complication, and patient satisfaction using a verbal numerical rating scale
      (VNRS) at 0, 1, 6, 12, 24, 48 h after the operation. RESULTS: All patients had
      successful ISBPB and excellent analgesic effects less than VNRS 4 up to discharge
      time. VNRS in Group II at 12 h and 48 h was statistically much lower than in
      Group I and III. There were no differences in total analgesic consumption, sleep
      quality, complications, and patient satisfaction. CONCLUSIONS: We conclude that
      the addition of 5 mg of dexamethasone to 10 ml of 0.5% levobupivacaine in ISBPB
      showed improvement of postoperative analgesia for arthroscopic shoulder operation
      without any specific complications.

PMID- 22379568
TI  - Low-dose remifentanil to modify hemodynamic responses to tracheal intubation:
      comparison in normotensive and untreated/treated hypertensive Korean patients.
AB  - BACKGROUND: Remifentanil has been shown to be effective at treating potentially
      adverse hemodynamic responses to tracheal intubation even at low doses (< 1
      ug/kg/min), which needs to be evaluated in patients with diverse cardiovascular
      conditions. METHODS: A low-dose regimen of remifentanil (continuous infusion of
      0.1 ug/kg/min, preceded by 0.5 ug/kg bolus) was given before induction with bolus
      propofol and rocuronium, and heart rate as well as systolic, diastolic, and mean
      arterial pressures were measured at 1 min intervals from before induction to 5
      min after tracheal intubation in normotensive patients, untreated hypertensive
      patients, and patients with known hypertension. RESULTS: The low-dose regimen of
      remifentanil resulted in parallel hemodynamic responses in all three groups, and
      was effective at limiting hemodynamic responses to tracheal intubation without
      excessive cardiovascular depression. Hemodynamic responses in our study showed a
      similar pattern to that reported in previous investigations, except for
      elevations in heart rate and arterial pressures over the baseline values
      immediately after intubation. CONCLUSIONS: We suggest that the low-dose regimen
      of remifentanil in our study could be routinely used to modify hemodynamic
      responses to tracheal intubation in patients with diverse hemodynamic
      characteristics. However, the development of supplementary regimens is still
      needed to control the brief, but exaggerated responses to tracheal intubation,
      especially in untreated hypertensive patients.

PMID- 22379569
TI  - Effect of ketamine on intravenous patient-controlled analgesia using
      hydromorphone and ketorolac after the Nuss surgery in pediatric patients.
AB  - BACKGROUND: Nuss surgery is preferred in pectus excavatum repair because this
      procedure produces excellent cosmetic results and prevents postoperative
      distressed pulmonary function. However, the procedure causes severe pain due to
      thoracic expansion. This study was designed to investigate the analgesic effect
      of small doses of ketamine on an intravenous patient-controlled analgesia (IV
      PCA) using hydromorphone and ketorolac for pain control after Nuss surgery.
      METHODS: Forty-four patients undergoing elective Nuss surgery were randomly
      assigned to receive hydromorphone 3 ug/kg/hr, ketorolac 0.05 mg/kg/hr and
      ondansetron 0.1 mg/kg/day (Group HO, n = 22) or hydromorphone 3 ug/kg/hr,
      ketorolac 0.05 mg/kg/hr, ondansetron 0.1 mg/kg/day and ketamine 0.15 mg/kg/hr
      (Group HK, n = 22) via an IV-PCA pump after surgery. A blind observer evaluated
      each patient using the Modified Children's Hospital of Eastern Ontario Pain Scale
      (CHEOPS) for the assessment of pain control. The total administered PCA volume,
      side effects and parents satisfaction with pain control were assessed at
      postoperative 1, 4, 8, 12, 24, and 48 hours. RESULTS: There were no significant
      differences in Modified CHEOPS between the groups during postoperative 48 hours.
      The total PCA volume in group HK was significantly lower than that in group HO (P
      < 0.05). The side effects in both groups did not significantly differ except for
      pruritus. The levels of satisfaction from the parents were not significantly
      different between the groups. CONCLUSIONS: A small dose of ketamine on IV-PCA
      reduced the total administered dose of IV-PCA with hydromorphone and ketorolac
      and reduced the incidence of pruritus after the Nuss procedure in pediatric
      patients.

PMID- 22379570
TI  - Effects of ulinastatin treatment on myocardial and renal injury in patients
      undergoing aortic valve replacement with cardiopulmonary bypass.
AB  - BACKGROUND: We determined the protective effects of a high dose of ulinastatin on
      myocardial and renal function in patients undergoing aortic valve replacement
      with cardiopulmonary bypass (CPB). METHODS: Sixty patients were assigned randomly
      to either the ulinastatin group (n = 30) or the control group (n = 30). In the
      ulinastatin group, ulinastatin (300,000 U) was given after the induction of
      anesthesia, ulinastatin (400,000 U) was added to the CPB pump prime, and then
      ulinastatin (300,000 U) was administered after weaning from CPB. In the control
      group, the same volume of saline was administered at the same time points.
      Creatine kinase-MB levels were assessed 1 day before surgery, and on the first
      and second postoperative day (POD 1 and 2). Serum creatinine and cystatin C
      levels were assessed 1 day before surgery, upon intensive care unit arrival, and
      on POD 1 and 2. The level of plasma neutrophil gelatinase-associated lipocalin
      was assessed before induction of anesthesia, upon ICU arrival, and on POD 1.
      RESULTS: No significant differences were observed in serum levels of creatine
      kinase-MB and biomarkers of renal injury between the two groups at any point
      during the study period. CONCLUSIONS: Ulinastatin showed no cardiac or renal
      protective effects after CPB in patients undergoing aortic valve replacement.

PMID- 22379571
TI  - Relation between preoperative autonomic function and blood pressure change after
      tourniquet deflation during total knee replacement arthroplasty.
AB  - BACKGROUND: Tourniquets are used to provide a bloodless surgical field for
      extremities. Hypotension due to vasodilation and bleeding after tourniquet
      deflation is a common event. Hemodynamic stability is modulated by the autonomic
      nervous system (ANS). Heart rate variability (HRV) is a sensitive method for
      detecting individuals who may be at risk of hemodynamic instability during
      general anesthesia. The purpose of this study was to investigate ANS function to
      predict hypotension after tourniquet deflation. METHODS: Eighty-six patients who
      underwent total knee replacement arthroplasty (TKRA) were studied. HRV, systolic
      blood pressure variability (SBPV) and baroreflex sensitivity (BRS) were analyzed.
      We assigned two groups depending on the lowest systolic blood pressure (SBP) or
      mean BP (MBP) after tourniquet release (Group H; SBP < 80 mmHg or MBP < 60 mmHg,
      Group S; SBP > 80 mmHg and MBP > 60 mmHg). RESULTS: Fifteen patients developed
      severe hypotension and ten patients were treated with ephedrine. Of the
      parameters of HRV, SBPV, and BRS, only BRS(SEQ) was significant being low in
      Group H. BRS and high-frequency SBPV were correlated with the degree of MBP
      change after tourniquet deflation. CONCLUSIONS: Preoperative low BRS is
      associated with hypotension after tourniquet deflation, suggesting the importance
      of baroreflex regulation for intraoperative hemodynamic stability.

PMID- 22379572
TI  - Effect of manassantin B, a lignan isolated from Saururus chinensis, on
      lipopolysaccharide-induced interleukin-1beta in RAW 264.7 cells.
AB  - BACKGROUND: Elevated systemic levels of pro-inflammatory cytokines cause
      hypotension during septic shock and induce capillary leakage in acute lung
      injury. Manassantin B has anti-inflammatory and anti-plasmoidal properties. This
      study examined the effects of manassantin B on lipopolysaccharide (LPS)-induced
      inflammatory response in murine macrophages. METHODS: RAW 264.7 macrophage cells
      were incubated without or with (1, 3 and 10 uM) manassantin B and without or with
      (100 ng/ml) LPS. Manassantin B dissolved in phosphate buffered saline was added
      to the medium 1 h prior to the addition of LPS. The degree of activation of
      mitogen-activated protein kinase (MAPK) including extracellular signal-regulated
      kinases 1 and 2 (ERK1/2), c-Jun amino terminal kinases (JNK) and p38 MAPK, and
      the level of interleukin (IL)-1beta were determined 30 min and 24 h after the
      addition of LPS respectively. RESULTS: Manassantin B inhibited the production of
      IL-1beta and attenuated the phosphorylations of ERK1/2 and p38 MAPK, but not that
      of JNK, in RAW 264.7 cells treated with LPS. CONCLUSIONS: Manassantin B reduces
      LPS-induced IL-1beta expression through effects on ERK1/2- and p38 MAPK-mediated
      pathways. Manassantin B has potential as a potent anti-inflammatory drug for use
      in pathological processes such as sepsis or acute lung injury.

PMID- 22379573
TI  - Midazolam protects B35 neuroblastoma cells through Akt-phosphorylation in
      reactive oxygen species derived cellular injury.
AB  - BACKGROUND: Soman, a potent irreversible acetylcholinesterase (AChE) inhibitor,
      induces delayed neuronal injury by reactive oxygen species (ROS). Midazolam is
      used in patients with pathologic effects of oxidative stresses such as infection,
      hemodynamic instability and hypoxia. We investigated whether midazolam protects
      the Central Nervous System (CNS) from soman intoxication. The present study was
      performed to determine whether midazolam protects B35 cells from ROS stress for
      the purpose of exploring an application of midazolam to soman intoxication.
      METHODS: Glucose oxidase (GOX) induced ROS stress was used in a B35 neuroblastoma
      cell model of ROS induced neuronal injury. To investigate the effect of midazolam
      on cell viability, LDH assays and fluorescence activated cell sorting (FACS)
      analysis was performed. Western blotting was used for evaluating whether Akt
      phosphorylation is involved in cell-protective effects of midazolam. RESULTS: GOX
      derived ROS injury decreased cell viability about 1.6-2 times compared to
      control; midazolam treatment (5 and 10 ug/ml) dose-dependently increased cell
      viability during ROS injury. On western blots, Akt-phosphorylation was induced
      during pretreatment with midazolam; it was diminished during co-treatment with LY
      294002, an inhibitor of Akt-phosphorylation. FACS analysis confirmed that the
      cell protective effect of midazolam is mediated by an anti-apoptotic effect. GOX
      induced apoptosis was inhibited by midazolam and the finding was diminished by LY
      294002. CONCLUSIONS: Midazolam protects neuronal cells from GOX-induced ROS
      injury; this effect is mediated by an anti-apoptotic effect through Akt
      phosphorylation. This shows that midazolam may be useful in soman intoxication.

PMID- 22379574
TI  - Anesthetic management of penetrating neck injury patient with embedded knife -A
      case report-.
AB  - Penetrating neck injuries can be a fatal event and they are difficult to manage
      for both surgeons and anesthesiologists. So, adequate preoperative evaluation is
      important to improve the patients' outcomes, but this can not be done for
      hemodynamically unstable or uncooperative patient. Here we present our clinical
      experience with a patient with a penetrating neck injury and who was
      hemodynamically stable, but she was uncooperative and the knife was still
      embedded in her neck. The surgical exploration and bronchoscopic examination were
      successfully done under monitored anesthesia care.

PMID- 22379575
TI  - Abrupt formation of intracardiac thrombus during cardiopulmonary bypass with full
      heparinization -A case report-.
AB  - Intracardiac thrombus during cardiopulmonary bypass (CPB) with full
      heparinization is very rare but fatal. A 60-year-old woman was scheduled for
      aortic and mitral valve repairs with a maze procedure for mixed aortic and mitral
      valvular heart disease with atrial fibrillation. Preoperative transthoracic
      echocardiography and cardiac computed tomography showed moderate aortic
      regurgitation and moderate mitral stenosis with regurgitation. There was no
      intracardiac thrombus. Aortic and mitral valve repairs with the maze procedure
      were successfully performed without unexpected events. During CPB weaning, a
      mobile hyper-echogenic mass in the left atrium was detected on transesophageal
      echocardiography. After cardiac arrest, it was surgically removed. On completion
      of the operation, weaning from CPB was accomplished uneventfully. The patient
      fully recovered and was discharged from the intensive care unit on her third
      postoperative day.

PMID- 22379576
TI  - Experience of severe desaturation during anesthetic induction period in an obese
      adult patient with Prader-Willi syndrome -A case report-.
AB  - Prader-Willi syndrome is characterized by infantile hypotonia, childhood-onset
      obesity, short stature, mental retardation, hyperphagia, hypogonadism. After
      infantile hypotonia phase, patient is prone to morbid obesity due to hyperphagia.
      Complications associated with morbid obesity are recognized as the main risk
      factors for death the lifespan of patients with Prader-Willi syndrome. We
      experienced desaturation and bronchospasm during arteriovenous fistula surgery in
      an obese adult with Prader-Willi syndrome.

PMID- 22379577
TI  - Airway fire injury during rigid bronchoscopy in a patient with a silicon stent -A
      case report-.
AB  - Therapeutic bronchoscopy is widely employed as an effective first-line treatment
      for patients with central airway obstructions. Airway fires during rigid
      bronchoscopy are rare, but can have potentially devastating consequences.
      Pulmonologist and anesthesiologist undertaking this type of procedure should be
      aware of this serious problem and be familiar with measures to avoid this
      possibly fatal complication. We report the case of a 24-year-old patient with a
      silicone stent who experienced an electrocautery-induced airway fire during rigid
      bronchoscopy.

PMID- 22379578
TI  - Lumbar plexopathy after radical nephrectomy -A case report-.
AB  - Lumbar plexopathy is characterized by an abrupt onset of sensory disturbances,
      weakness, and loss of deep tendon reflexes of lower extremities. The various
      causes of lumbar plexopathy include trauma, infections, space-occupying lesion,
      vascular diseases, metabolic diseases, and the use of drugs such as heroin.
      Postoperative rhabdomyolysis occurs secondary to prolonged muscle compression due
      to surgical positioning. Herein, we report a case of lumbar plexopathy,
      complicating an injury to the paraspinal muscle and iliopsoas muscle that
      occurred in the flexed lateral decubitus position following radical nephrectomy.

PMID- 22379579
TI  - Guillain-Barre syndrome after lumbar epidural block.

PMID- 22379580
TI  - Anesthetic management of a patient with nitric acid inhalation injury for
      extracorporeal membrane oxygenation.

PMID- 22379581
TI  - Endotracheal intubation using a fiberoptic bronchoscope and laryngeal mask airway
      in ICU.

PMID- 22379582
TI  - Tension pneumothorax after ultrasound guided internal jugular venous
      catheterization in an inadvertently endobronchially intubated patient with
      kyphosis.

PMID- 22379583
TI  - Chronic prostatitis: approaches for best management.
AB  - Prostatitis is a prevalent condition that encompasses a large array of clinical
      symptoms with significant impacts on men's life. The diagnosis and treatment of
      this disorder presents numerous challenges for urologists, most notably, a lack
      of specific and effective diagnostic methods. Chronic bacterial prostatitis is
      successfully treated with appropriate antibiotics that penetrate the prostate and
      kill the causative organisms. Prostatitis category III (chronic pelvic pain
      syndrome) is common, very bothersome, and enigmatic. Symptoms are usually
      prolonged and, generally speaking, treatment results are unsatisfactory. During
      the last decade, research has focused on the distress caused by the condition,
      but although our knowledge has certainly increased, there have been no real
      breakthroughs; controversies and many unanswered questions remain. Furthermore,
      the optimal management of category III prostatitis is not known. Conventional
      prolonged courses of antibiotic therapy have not proven to be efficacious. Novel
      therapies providing some evidence for efficacy include alpha-blocker, anti
      inflammatory phytotherapy, physiotherapy, neuroleptics, and others, each offering
      therapeutic mechanisms. A stepwise approach involving multimodal therapy is often
      successful for treating patients. The UPOINT technique has been used to
      clinically phenotype these patients and drive the appropriate selection of
      multimodal therapy.

PMID- 22379584
TI  - The direct anti-cancer effect of a single instillation of epirubicin after
      transurethral resection of bladder tumor for non-muscle-invasive bladder cancer.
AB  - PURPOSE: To evaluate the direct anti-cancer effect of a single instillation of
      epirubicin (SIE) after transurethral resection of bladder tumor (TURBT) for non
      muscle-invasive bladder cancer (NMIBC) by analysis of immediate urine cytology
      (IUC). MATERIALS AND METHODS: We reviewed the records of 158 patients who had IUC
      after TURBT for NMIBC. Fifty-six patients were treated with SIE after TURBT and
      102 patients were not treated with SIE. The direct anti-cancer effect of SIE was
      compared in the two groups according to the result of IUC. The relationship
      between SIE and IUC in NMIBC was analyzed by use of multivariate Cox proportional
      hazards regression models. RESULTS: The IUC-positive rate was 33.9% in the SIE
      group and 42.1% in the non-SIE group (p=0.005). The IUC-positive rate was lower
      in the SIE group than in the non-SIE group for each factor, including tumor
      stage, tumor grade, tumor size, tumor multiplicity, and preoperative urine
      cytology. Multivariate Cox proportional hazards regression analysis revealed that
      SIE was significantly associated with a negative IUC result in patients with
      NMIBC (HR, 0.163) (p<0.001). CONCLUSIONS: These results indicate the direct anti
      cancer effect of SIE in patients who undergo TURBT for NMIBC.

PMID- 22379585
TI  - Is prostate biopsy essential to diagnose prostate cancer in the older patient
      with extremely high prostate-specific antigen?
AB  - PURPOSE: The results of all prostate biopsies may be positive and suggestive of
      adenocarcinoma in patients with prostate-specific antigen (PSA) values higher
      than 100 ng/ml. We considered that the prostate cancer in patients with high PSA
      might be advanced disease and therefore that the treatment strategy should not be
      changed according to pathological reports. Thus, we assessed the role of prostate
      biopsy when diagnosing prostate cancer in patients with extremely high PSA
      levels. MATERIALS AND METHODS: We reviewed the records of 1,150 cases undergoing
      prostate biopsies. Patients with urinary tract infection and acute urinary
      retention were excluded. According to the pre-biopsy PSA level, patients were
      divided into 6 groups (group A, 4 to 20 ng/ml; B, 20 to 40 ng/ml; C, 40 to 60
      ng/ml; D, 60 to 80 ng/ml; E: 80 to 100 ng/ml; and F, above 100 ng/ml). RESULTS:
      The calculated positive predictive value (PPV) for prostate cancer was 22% in
      group A, 54% in group B, 73% in group C, 75% in group D, 89% in group E, and 100%
      in group F, respectively. Pathological diagnosis was adenocarcinoma in all
      patients in group F (n=56). Among them, 38 patients (67.9%) had lymph node
      metastasis or extra-prostatic disease or both and 43 patients (76.8%) had bony
      metastasis. In group F, all cases were advanced prostate cancer (stage III or
      IV). All of them received hormonal therapy following diagnosis. CONCLUSIONS: We
      suggest the possibility for biopsy-free diagnosis of prostate cancer in patients
      with extremely high levels of serum PSA and evidence of advanced disease in
      imaging studies, especially in older patients with comorbid medical problems.

PMID- 22379586
TI  - Prostate Biopsy in the Left Lateral Decubitus Position is Less Painful than
      Prostate Biopsy in the Lithotomy Position: A Randomized Controlled Trial.
AB  - PURPOSE: The primary objective was to assess whether transrectal ultrasound
      (TRUS)-guided prostate biopsy in the left lateral decubitus (LLD) position
      differed from the procedure in the lithotomy position regarding patients' pain
      perception. The secondary objective was to assess the analgesic effect of
      intrarectal 2% lidocaine gel in this setting. MATERIALS AND METHODS: This single
      center, open-label trial enrolled 148 men undergoing prostate biopsy. Then men
      were randomly assigned to group 1 (LLD position, no lidocaine, n=50, "test"),
      group 2 (lithotomy position+lidocaine, n=50, "positive control"), and group 3
      (lithotomy position, no lidocaine, n=48, "negative control"). Twelve-core samples
      were taken in each biopsy set. Pain was assessed by using a 10-point visual
      analogue scale (VAS). RESULTS: Across the groups, patients were comparable
      regarding age, prostate-specific antigen levels, prostate volume, digital rectal
      examination findings, and pathohistological diagnosis. VAS scores were lower in
      group 1 (median, 2.95) than in group 2 (median, 4.95; p<0.001) or group 3
      (median, 4.60; p<0.001). The difference between group 2 and group 3 was
      insignificant (p=0.268). The adjusted mean differences (with adjustment for the
      above covariates) were as follows: group 1 vs. group 2, -1.43 (95% confidence
      interval [CI]: -2.25 to -0.60; p<0.001); group 1 vs. group 3, -1.22 (95% CI: 
      2.04 to -0.41; p=0.001); group 2 vs. group 3, 0.20 (95% CI, -0.63 to 1.04;
      p=0.836); and group 1 vs. groups 2 and 3, -1.33 (95% CI, -1.92 to -0.73;
      p<0.001). The procedure was comparably well tolerated across the groups.
      CONCLUSIONS: Pain perception during prostate biopsy was lower in the LLD position
      than in the lithotomy position. Intrarectal 2% lidocaine gel does not seem to
      affect pain perception.

PMID- 22379587
TI  - Efficacy of alpha blocker treatment according to the degree of intravesical
      prostatic protrusion detected by transrectal ultrasonography in patients with
      benign prostatic hyperplasia.
AB  - PURPOSE: To analyze the effectiveness of tamsulosin 0.2 mg once daily for 3
      months according to the degree of intravesical prostatic protrusion (IPP) in
      patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total
      of 134 BPH patients over 40 years of age treated with tamsulosin 0.2 mg between
      January 2007 and January 2009 were enrolled retrospectively. The patients were
      classified into three groups according to the degree of IPP: below 5 mm (group
      A), between 5 and 10 mm (group B), and over 10 mm (group C). Prostate volume,
      prostate-specific antigen (PSA), prostatic urethral length (PUL), and prostatic
      adenoma urethral length (PAUL) were evaluated before treatment. International
      Prostate Symptom Score and Quality of Life (IPSS/QoL), maximal urine flow rate
      (Qmax), and postvoid residual (PVR) volume were measured before treatment, and
      improvement in the three groups was compared after 3 months. RESULTS: The mean
      age of the patients was 65.01+/-7.38 years. Mean IPPs were 0.90+/-1.39 mm (group
      A, n=90), 6.92+/-1.10 mm (group B, n=24), and 16.60+/-4.06 mm (group C, n=20).
      Prostate volume, PUL, PAUL, PSA, Qmax, and PVR showed significant correlations
      with IPP (p<0.05), but not with IPSS/QoL score (p>0.05). Comparison of parameters
      before and after 3 months showed that medication improved total IPSS and
      subscores (p<0.001), QoL (p<0.001), Qmax (p<0.001), and PVR (p=0.030) in group A.
      In group B, it improved total IPSS (p=0.01), irritative subscore (p<0.001), and
      obstructive subscore (p=0.03). In group C, only total IPSS (p=0.01) and
      irritative score (p<0.001) were significantly improved. CONCLUSIONS: Tamsulosin
      may be more effective in improving symptom scores and Qmax in patients with mild
      IPP than in those with moderate or severe IPP.

PMID- 22379588
TI  - A Comparison of the Clinical Efficacy of the Transobturator Adjustable Tape (TOA)
      and Transobturator Tape (TOT) for Treating Female Stress Urinary Incontinence
      with Intrinsic Sphincter Deficiency: Short-term Results.
AB  - PURPOSE: The transobturator adjustable tape (TOA) allows adjustment of tension
      after surgical intervention, thus permitting correction of postoperative
      incontinence or obstruction. The aim of this study was to compare the efficacy
      and safety of TOA versus transobturator tape (TOT) for the treatment of stress
      urinary incontinence with intrinsic sphincter deficiency (ISD). MATERIALS AND
      METHODS: Patients underwent TOA (n=33 with ISD) or TOT (n=47 with ISD) insertion
      by one experienced surgeon. The patients were considered to have ISD on the basis
      of a Valsalva leak point pressure <60 cmH(2)O or a maximum urethral closure
      pressure <20 cmH(2)O. The preoperative evaluation included history taking,
      physical examination, voiding diary, stress and 1-hour pad tests, and a
      comprehensive urodynamic examination. Postoperative evaluation included a stress
      test, 1-hour pad test, questionnaire, and uroflowmetry with postvoid residuals.
      RESULTS: After 6 months of follow-up, the rate of cure (TOA, 75.6% vs. TOT,
      72.3%) was similar between the two groups. The rate of satisfaction was not
      significantly higher in the TOA group than in the TOT group (84.8% vs. 78.7%;
      p=0.05). Four patients in the TOA group (12.1%) needed a reduction in tension
      because of urinary obstruction (flow <10 ml/sec and/or residual urine >50 ml).
      The tension of the mesh was tightened in 5 patients (15.2%) because of the
      persistence of a certain degree of incontinence. The residual urine volume at
      postoperative 7 days was significantly lower in the TOA group than in the TOT
      group (19.5 ml vs. 41 ml; p=0.016, repeated-measures analysis of variance test).
      CONCLUSIONS: The TOA allows postoperative readjustment of the suburethral sling
      pressure for a number of days after surgical intervention, which allows for the
      achievement of good short-term results. These data suggest that better lower
      obstructive voiding symptoms than those achieved with the traditional
      nonadjustable mesh can be obtained with the TOA.

PMID- 22379589
TI  - Serial Changes in Sexual Function Following Holmium Laser Enucleation of the
      Prostate: A Short-term Follow-up Study.
AB  - PURPOSE: To evaluate the serial changes in sexual function in the short-term
      period after holmium laser enucleation of the prostate (HoLEP) for benign
      prostatic hyperplasia (BPH) and to investigate whether a change in each domain of
      the International Index of Erectile Function (IIEF) is associated with
      improvement of micturition. MATERIALS AND METHODS: Thirty-eight potent men who
      underwent HoLEP and in whom complete 12-month follow-up data on the IIEF were
      available were included in this retrospective study. All patients underwent a
      baseline evaluation for BPH. The surgical outcome was evaluated at 1, 3, 6, and
      12 months postoperatively by use of the International Prostate Symptom Score,
      IIEF, and uroflowmetry. RESULTS: The mean age and body mass index of the patients
      was 64.5+/-6.2 years and 24.2+/-2.6 kg/m(2), respectively. Mean total prostate
      volume and transitional zone volume were 48.8+/-18.8 ml and 24.2+/-16.1 ml,
      respectively. Most IIEF domain scores showed a slight decrease at 1, 3, and 6
      months after surgery but recovered to the baseline or showed a marginal but
      nonsignificant increase at 12 months postoperatively compared with baseline.
      Orgasmic function and the overall sexual satisfaction domain score remained
      slightly reduced up to 12 months postoperatively. There was no significant
      correlation between improvement of micturition and change in sexual function
      throughout the follow-up period after surgery. CONCLUSIONS: Although HoLEP
      achieves significant improvements in micturition, overall sexual function
      decreases slightly in the early postoperative period, but recovers to the
      baseline at 12 months postoperatively. Our data suggest that changes in sexual
      function after HoLEP are not associated with improvement of micturition.

PMID- 22379590
TI  - Effect of prostatitis on lower urinary tract symptoms: retrospective analysis of
      prostate biopsy tissue.
AB  - PURPOSE: Most patients, even some urologists, assume that prostate volume is the
      most important prognostic factor for lower urinary tract symptoms (LUTS). In some
      cases, however, prostatic inflammation is a more important factor in LUTS than is
      prostate volume. For this reason, comparison of the impact on LUTS of
      inflammation and prostate volume is an attractive issue. MATERIALS AND METHODS:
      From January 2000 to May 2009, 1,065 men aged between 47 and 91 years (who
      underwent transrectal ultrasound-guided prostate needle biopsy and transurethral
      prostatectomy) were retrospectively investigated. Components such as age, serum
      prostate-specific antigen (PSA) level, prostate volume, and the presence of
      prostatitis were investigated through independent-sample t-tests, chi-square
      tests, and univariate and multivariate analyses. RESULTS: Chi-square tests
      between prostatitis, prostate volume, serum PSA, and severe LUTS showed that
      prostate volume (R=0.173; p=0.041) and prostatitis (R=0.148; p<0.001) were
      related to LUTS. In particular, for a prostate volume under 50 ml, prostatitis
      was a stronger risk factor than was prostate volume. Among the multivariate
      predictors, prostatitis (odds ratio [OR]: 1.945; p<0.001) and prostate volume
      (OR, 1.029; p<0.001) were found to be aggravating factors of LUTS. CONCLUSIONS:
      For patients with prostate volume less than 50 ml, prostatitis was found to be a
      more vulnerable factor for LUTS. For those with prostate volume over 50 ml, on
      the other hand, the volume itself was a more significant risk factor than was
      prostatitis. In conclusion, the presence of prostatitis is one of the risk
      factors for LUTS with increased prostate volume.

PMID- 22379591
TI  - Diagnostic value of functional bladder capacity, urine osmolality, and daytime
      storage symptoms for severity of nocturnal enuresis.
AB  - PURPOSE: To investigate the correlation between functional bladder capacity,
      first morning urine osmolality, daytime voiding symptoms, and severity of
      nocturnal enuresis. MATERIALS AND METHODS: We assessed a total of 101 children
      with nocturnal enuresis (mean age, 7.7+/-2.3 years). Patients were divided into
      three groups according to the severity of enuresis: (1) one to six episodes per
      week (46 cases, 45.5%), (2) one episode every day (29 cases, 28.7%), and (3)
      multiple episodes every day (26 cases, 25.8%). Baseline parameters were obtained
      from frequency volume charts for 2 days, first morning urine osmolality, and a
      questionnaire for the presence of frequency, urgency, and daytime incontinence.
      RESULTS: The severity of enuresis increased with younger age (p=0.037) and
      reduced functional bladder capacity (p=0.007) and daytime symptoms of frequency
      and daytime incontinence (p=0.012, p=0.036). No statistical difference in urine
      osmolality or urgency was found among the three groups. Both reduced functional
      bladder capacity and low urine osmolality increased according to the severity of
      enuresis (p=0.012). CONCLUSIONS: In children with nocturnal enuresis, severity
      was increased by younger age, reduced functional bladder capacity, and the
      presence of daytime voiding symptoms of frequency and daytime incontinence. The
      incidence of small functional bladder capacity was increased in children with
      everyday wetting, and the incidences of both small functional bladder capacity
      and low urine osmolality were increased in children with everyday multiple
      wetting.

PMID- 22379592
TI  - Ureteral injury in gynecologic surgery: a 5-year review in a community hospital.
AB  - PURPOSE: We reviewed the cases of ureteral injury during gynecologic surgeries in
      a community hospital and attempted to find possible options for alleviating these
      distressing situations. MATERIALS AND METHODS: A total of 2,927 patients
      underwent gynecologic surgeries in the last 5 years at our hospital. We
      retrospectively analyzed the cases, particularly the possible risk factors and
      management according to the time of detection of the injury. Thirty-five cases
      (1.2%) were identified with ureteral injury in a total of 2,927 gynecologic
      surgeries. Risk factors included endometriosis, pelvic inflammatory disease,
      previous pelvic surgery, history of pelvic radiation, and congenital anomalies.
      Among 2,927 patients, 522 had predisposing factors for ureteral injuries.
      RESULTS: The incidence of ureteral injury in laparoscopic cases was 1.1%, similar
      to the cases of laparotomy (1.2%). The rate of ureteral injury was significantly
      higher in the group with risk factors (2.7%) than in the group without risk
      factors (0.9%; p=0.002). Prophylactic ureteral stenting was performed in 101 of
      522 patients with risk factors according to the gynecologic surgeon's preference.
      The injury rate (1.0%) in the stenting group was lower than that in the non
      stenting group (3.1%; p=0.324). Management of ureteral injuries was successful in
      all cases. Of the patients with postoperatively diagnosed injuries, two patients
      were managed with secondary procedures, such as retrograde balloon dilatation or
      ureteroneocystostomy. CONCLUSIONS: The incidence of ureteral injury was
      significantly higher in cases having risk factors than in cases without risk
      factors. Surgeons should be cautious to avoid ureteral injury during gynecologic
      surgery, especially in patients with risk factors.

PMID- 22379593
TI  - Influence of Donor's Renal Function on the Outcome of Living Kidney
      Transplantation: 10-Year Follow-up.
AB  - PURPOSE: With the improved surgical techniques and immunosuppression available
      today, conventional prognostic factors have taken on less significance.
      Accordingly, the native renal function of the donor is thought to be more
      important. Thus, we analyzed the prognostic significance of the donor's renal
      function as assessed by 24-hour urine creatinine clearance on kidney graft
      survival for 10 years after living kidney transplantation. MATERIALS AND METHODS:
      From January 1998 to July 2000, 71 living kidney transplantations were performed
      at a single institution. From among these, 68 recipients were followed for more
      than 6 months and were included in the present analysis. We analyzed kidney graft
      survival according to clinical parameters of the donor and the recipient.
      RESULTS: Mean follow-up duration of recipients after living kidney
      transplantation was 115.0+/-39.4 months (range, 10 to 157 months), and 31
      recipients (45.6%) experienced kidney graft loss during this time period.
      Estimated mean kidney graft survival time was 131.8+/-6.2 months, and 5-year and
      10-year kidney graft survival rates were estimated as 88.2% and 61.0%,
      respectively. Donor's mean 24-hour urine creatinine clearance (Ccr) before kidney
      transplantation was 122.8+/-21.2 ml/min/1.73 m(2) (range, 70.1 to 186.6
      ml/min/1.73 m(2)). The 10-year kidney graft survival rates for cases stratified
      by a donor's Ccr lower and higher than 120 ml/min/1.73 m(2) were 39.0% and 67.2%,
      respectively (p=0.005). In univariate and multivariate analysis, donor's Ccr was
      retained as an independent prognostic factor of kidney graft survival (p=0.001
      and 0.005, respectively). CONCLUSIONS: Donor's 24-hour urine Ccr before living
      kidney transplantation was an independent prognostic factor of kidney graft
      survival. Therefore, it should be considered before living kidney
      transplantation.

PMID- 22379594
TI  - A rare case of upper ureter rupture: ureteral perforation caused by urinary
      retention.
AB  - Perforation of the ureter is a rare condition that causes a series of problems
      including retroperitoneal urinoma, urosepsis, abscess formation, infection, and
      subsequent renal impairment. There are causative factors that induce ureteric
      rupture, including malignancy, urinary calculi, idiopathic retroperitoneal
      fibrosis, recent iatrogenic manipulation, external trauma, degenerative kidney
      conditions, urography with external compression, and spontaneous causes. We
      report a rare case of ureteric rupture caused by urinary retention. The patient
      was treated with temporary percutaneous drainage and antibiotics. The present
      case illustrates that urinary retention can induce not only bladder rupture, but
      also ureteric rupture. It is thus of paramount importance to effectively manage
      patients with voiding problems.

PMID- 22379595
TI  - Myotonic dystrophy type 1 presenting as male infertility.
AB  - Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine
      defects that include testicular and tubular atrophy, oligospermia and
      azoospermia, and increased follicle-stimulating hormone levels. We describe a
      rare case of DM1 presenting as infertility in a 29-year-old man.

PMID- 22379596
TI  - Cor Triatriatum Sinistrum: Classification and Imaging Modalities.
AB  - Cor Triatriatum Sinister is a rare congenital abnormality, usually diagnosed in
      childhood; few cases remain asymptomatic and are diagnosed in adulthood. In this
      review article we focus on classification and etiologies, clinical
      manifestations, novel diagnostic modalities and treatment of Cor triatriatum
      Sinister.

PMID- 22379597
TI  - A measure of individual role in collective dynamics.
AB  - Identifying key players in collective dynamics remains a challenge in several
      research fields, from the efficient dissemination of ideas to drug target
      discovery in biomedical problems. The difficulty lies at several levels: how to
      single out the role of individual elements in such intermingled systems, or which
      is the best way to quantify their importance. Centrality measures describe a
      node's importance by its position in a network. The key issue obviated is that
      the contribution of a node to the collective behavior is not uniquely determined
      by the structure of the system but it is a result of the interplay between
      dynamics and network structure. We show that dynamical influence measures
      explicitly how strongly a node's dynamical state affects collective behavior. For
      critical spreading, dynamical influence targets nodes according to their
      spreading capabilities. For diffusive processes it quantifies how efficiently
      real systems may be controlled by manipulating a single node.

PMID- 22379598
TI  - QUANTITATIVE RT-PCR ANALYSES OF FIVE EVOLUTIONARY CONSERVED GENES IN ALLIGATOR
      BRAINS DURING DEVELOPMENT.
AB  - Gene expression was investigated in the major brain subdivisions (telencephalon,
      diencephalon, midbrain and hindbrain) in a representative reptile, Alligator
      mississipiensis, during the later stages of embryonic development. The following
      genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2;
      synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of
      synaptophysin, which was only expressed in the telencephalon, all genes were
      expressed in all brain regions sampled at the time periods examined. For NaV1.1,
      gene expression varied according to brain area sampled. When compared with
      NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene
      expression of SV2a was the most robust of any of the genes examined. Of the other
      genes examined, although differences were noted, no statistically significant
      changes were found either between brain part or time interval. Although limited,
      the present analysis is the first quantitative mRNA gene expression study in any
      reptile during development. Together with future experiments of a similar nature,
      the present gene expression results should determine which genes are expressed in
      major brain areas at which times during development in Alligator. When compared
      with other amniotes, these results will prove useful for determining how gene
      expression during development influences adult brain structure.

PMID- 22379599
TI  - The Role of Mycoplasma pneumoniae Infection in Asthma.

PMID- 22379600
TI  - Asthma and Rhinitis in South America: How Different They are From Other Parts of
      the World.
AB  - Asthma and rhinitis epidemiology has wide variations around the world. The aim of
      this review was verify the prevalence of asthma and rhinitis in South America and
      report differences from other regions of the world. We reviewed studies with
      International Study of Asthma and Allergies in Childhood (ISAAC) methodology in
      South America, Phases I and III. In South America the ISAAC Phase I ranked four
      countries among top ten in prevalence of asthma and three countries among top ten
      in prevalence of rhinoconjunctivitis. ISAAC Phase III showed little changes in
      asthma and rhinitis prevalence in South American countries. The prevalence
      increases of asthma and rhinitis in South American centers indicate that the
      burden of both is continuing to rise, but the differences in prevalence are
      lessening.

PMID- 22379602
TI  - Predisposing factors associated with chronic and recurrent rhinosinusitis in
      childhood.
AB  - PURPOSE: There is currently no information regarding predisposing factors for
      chronic and recurrent rhinosinusitis (RS), although these are considered to be
      multifactorial in origin, and allergic diseases contribute to their pathogenesis.
      We evaluated the predisposing factors that may be associated with chronic and
      recurrent RS. METHODS: In this prospective study, we examined patients with RS
      younger than 13 years of age, diagnosed with RS at six tertiary referral
      hospitals in Korea between October and December, 2006. Demographic and clinical
      data related to RS were recorded and analyzed. RESULTS: In total, 296 patients
      were recruited. Acute RS was the most frequent type: 56.4% of the patients had
      acute RS. The prevalences of other types of RS, in descending order, were chronic
      RS (18.9%), subacute RS (13.2%), and recurrent RS (11.5%). Factors associated
      with recurrent RS were similar to those of chronic RS. Patients with chronic and
      recurrent RS were significantly older than those with acute and subacute RS. The
      prevalences of allergic rhinitis, atopy, and asthma were significantly higher in
      patients with chronic and recurrent RS than those with acute and subacute RS.
      CONCLUSIONS: An association between atopy and chronic/recurrent RS, compared to
      acute and subacute RS, suggests a possible causal link.

PMID- 22379601
TI  - Eosinophil development, regulation of eosinophil-specific genes, and role of
      eosinophils in the pathogenesis of asthma.
AB  - Eosinophils arise from hematopoietic CD34(+) stem cells in the bone marrow. They
      acquire IL-5Ralpha on their surface at a very early stage during
      eosinophilopoiesis, and differentiate under the strong influence of interleukin
      (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to
      airway inflammatory signals, including eotaxins. In inflamed tissues, eosinophils
      act as key mediators of terminal effector functions and innate immunity and in
      linking to adaptive immune responses. Transcription factors GATA-1,
      CCAAT/enhancer-binding protein, and PU.1 play instructive roles in eosinophil
      specification from multipotent stem cells through a network of cooperative and
      antagonistic interactions. Not surprisingly, the interplay of these transcription
      factors is instrumental in forming the regulatory circuit of expression of
      eosinophil-specific genes, encoding eosinophil major basic protein and
      neurotoxin, CC chemokine receptor 3 eotaxin receptor, and IL-5 receptor alpha.
      Interestingly, a common feature is that the critical cis-acting elements for
      these transcription factors are clustered in exon 1 and intron 1 of these genes
      rather than their promoters. Elucidation of the mechanism of eosinophil
      development and activation may lead to selective elimination of eosinophils in
      animals and human subjects. Furthermore, availability of a range of genetically
      modified mice lacking or overproducing eosinophil-specific genes will facilitate
      evaluation of the roles of eosinophils in the pathogenesis of asthma. This review
      summarizes eosinophil biology, focusing on development and regulation of
      eosinophil-specific genes, with a heavy emphasis on the causative link between
      eosinophils and pathological development of asthma using genetically modified
      mice as models of asthma.

PMID- 22379603
TI  - IgE Sensitization to Cephalosporins in Health Care Workers.
AB  - PURPOSE: Cephalosporins can induce occupational allergies, such as asthma,
      urticaria, and anaphylaxis. We investigated the prevalence and risk factors of
      sensitization to cephalosporin. METHODS: A total of 161 health care workers
      (HCW), including 138 nurses and 23 pharmacists, and 86 unexposed non-atopic
      healthy controls were recruited from a single tertiary hospital and the general
      population. A questionnaire regarding work-related symptoms was administered
      along with skin prick tests (SPT) to the three most commonly used cephalosporins
      (cefotiam, ceftriaxone, and ceftizoxime). Serum specific IgE antibodies to
      conjugates of the three cephalosporins and human serum albumin (HSA) were
      measured by enzyme-linked immunosorbent assay (ELISA). Binding specificities were
      confirmed by ELISA inhibition tests. RESULTS: The prevalence of work-related
      symptoms in association with cephalosporins was 17.4%. The sensitization rate to
      any cephalosporin was 3.1% by SPT. Sensitization rates determined by measurement
      of serum specific IgE antibodies were 17.4% for any cephalosporin, 10.4% for
      cefotiam, 6.8% for ceftriaxone, and 3.7% for ceftizoxime. A personal history of
      any antibiotic allergy was a risk factor for work-related symptoms (OR, 24.93;
      95% CI, 2.61-238), but not for the presence of serum specific IgE antibodies to
      cephalosporins (OR, 0.9; 95% CI, 0.18-4.53). A personal history of atopic
      dermatitis was a risk factor for the presence of serum specific IgE antibodies to
      cefotiam-HSA conjugate (OR, 6.30; 95% CI, 1.23-32.3). CONCLUSIONS: A high
      cephalosporin sensitization rate (17.4%) was detected by ELISA in HCW exposed to
      cephalosporins. Monitoring of serum specific IgEs to cephalosporin-HSA conjugates
      will be useful for detecting sensitized subjects.

PMID- 22379604
TI  - Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial
      Growth Factor and Interleukin-5 in Atopic Children.
AB  - PURPOSE: Previous studies have outlined mechanisms by which Mycoplasma pneumonia
      (M. pneumonia) infection may promote allergic lung inflammation and airway
      remodeling, and increasing evidence from human studies suggests that atypical
      bacterial infections contribute to asthma exacerbation, chronic asthma, and
      disease severity with changes in cytokine expression. The present study evaluated
      changes in serum levels of vascular endothelial growth factor (VEGF) and
      interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia.
      METHODS: We recruited a total of 72 children with pneumonia. The patients were
      divided into 4 groups: atopic children with M. pneumonia pneumonia (group I,
      n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic
      children with viral pneumonia (group III, n=13), and non-atopic children with
      viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor
      necrosis factor-alpha were measured at admission and at recovery using enzyme
      linked immunosorbent assays. RESULTS: Serum levels of VEGF and IL-5 were elevated
      in group I compared with the other groups at both admission phase and clinical
      recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery
      phase than at admission phase (VEGF: 1,102.2+/-569.4 vs. 874.9+/-589.9 pg/mL,
      respectively; IL-5: 150.5+/-63.9 vs. 120.2+/-46.7 pg/mL, respectively).
      CONCLUSIONS: The serum levels of VEGF and IL-5 were more increased in atopic
      children with M. pneumonia pneumonia than in the other groups. In this group, the
      serum levels of VEGF and IL-5 were more increased at recovery phase than at
      admission phase. The results of this study suggest that increases in VEGF and IL
      5 may contribute to the development of hypersensitivity during M. pneumonia
      infection. These cytokines may act through their respective pro-inflammatory
      pathways to aggravate the allergic status and induce airway hypersensitivity
      during M. pneumonia pneumonia in atopic children.

PMID- 22379605
TI  - Role of adipokines and hormones of obesity in childhood asthma.
AB  - PURPOSE: The aim of this study was to evaluate serum levels of leptin, ghrelin,
      and adiponectin in obese and non-obese children with asthma and in healthy non
      asthmatic children, and analyze their relationships with clinical outcomes.
      METHODS: This study enrolled 40 obese and 51 non-obese children with asthma and
      20 healthy children. Body mass index and serum leptin, ghrelin, and adiponectin
      levels were determined in all children. Asthma symptom scores and lung function
      test results were recorded for subjects with asthma. RESULTS: Serum leptin levels
      (11.8+/-7.9, 5.3+/-6.8, and 2.1+/-2.4 ng/mL in the obese asthmatic, non-obese
      asthmatic, and control groups, respectively) and adiponectin levels (12,586.2+/
      3,724.1; 18,089.3+/-6,452.3; and 20,297.5+/-3,680.7 ng/mL, respectively) differed
      significantly among the groups (P<0.001 for all). Mean ghrelin levels were
      196.1+/-96.8 and 311.9+/-352.8 pg/mL in the obese and non-obese asthmatic groups,
      respectively, and 348.8+/-146.4 pg/mL in the control group (P=0.001). The asthma
      symptom score was significantly higher in the obese children with asthma than in
      the non-obese children with asthma (P<0.001). Leptin and adiponectin levels were
      correlated with the asthma symptom score in non-obese children with asthma
      (r=0.34 and r=-0.62, respectively). CONCLUSIONS: Obesity leads to more severe
      asthma symptoms in children. Moreover, leptin, adiponectin, and ghrelin may play
      important roles in the inflammatory pathogenesis of asthma and obesity co
      morbidity.

PMID- 22379606
TI  - Occupational rhinitis induced by capsaicin.
AB  - Capsaicin is the spice component of red pepper. It can be easily inhaled,
      inducing a reproducible cough and provokes a secretory response from the human
      nasal mucosa. To date, there has been no report of occupational rhinitis (OR)
      caused by capsaicin. We report the case of a 44-year-old female mill worker who
      developed occupational rhinitis after 4 years of exposure to capsaicin. She
      developed nasal congestion, rhinorrhea, and itchy nose, which were all aggravated
      upon exposure at the workplace. The patient had negative responses to all common
      inhalant allergens, including capsaicin, by skin prick tests. The nasal
      provocation test with capsaicin showed that the nasal symptom score and
      eosinophil count increased 10 minutes after the provocation and decreased after 1
      to 3 hours; no significant response was noted to house dust mite allergen. The
      patient's work-related rhinitis improved 1 month after she relocated and started
      pharmacological treatment. To our knowledge, this is the first case of OR caused
      by capsaicin exposure in the workplace. We provide evidence suggesting that OR
      may be mediated by a non-immunological mechanism.

PMID- 22379607
TI  - A fatal case of intravascular coagulation after bee sting acupuncture.
AB  - Bee stings can cause severe adverse reactions, leading to anaphylaxis,
      cardiovascular collapse, and death. In some cases, bee venom also induces
      disseminated intravascular coagulation (DIC). However, to our knowledge, there
      has been no fatal case of intravascular coagulation accompanied by anaphylaxis
      caused by bee sting acupuncture. Here, we report a fatal case of a 65-year-old
      woman with DIC, following anaphylactic shock after bee sting acupuncture. This
      case emphasizes that practitioners should consider anaphylaxis followed by
      coagulation abnormalities when a patient's vital signs are unstable after bee
      sting acupuncture.

PMID- 22379608
TI  - A case of korean ginseng-induced anaphylaxis confirmed by open oral challenge and
      basophil activation test.
AB  - Two case reports discussing Korean ginseng-induced allergic reactions have been
      published; both were inhalation-induced respiratory allergies in occupational
      settings. In this report we discuss the first case of anaphylaxis that developed
      after an oral intake of ginseng, confirmed by an open oral challenge, a skin
      prick test (SPT), and a basophil activation test (BAT). A 44-year-old man
      experienced rhinorrhea and nasal stiffness, followed by respiratory difficulty
      with wheeze and abdominal pain 10 minutes after oral intake of fresh ginseng. He
      had suffered from episodes of allergic rhinitis during the spring season for
      several years. Upon presentation, a physical examination, chest radiograph, and
      routine laboratory tests were unremarkable. Total serum IgE level was 41 IU/mL.
      The SPT results showed strong positive responses to alder, birch pollens, and
      ginseng extracts (1:500 w/v). The methacholine bronchial challenge test revealed
      a positive result at PC20 of 5.83 mg/mL. The open oral challenge was performed
      using 50 g of fresh ginseng and showed immediate onset of facial flushing, cough,
      respiratory difficulty with wheeze, and abdominal pain combined with a
      significant decrease in FEV1 levels (54% from the baseline). Serum-specific IgE
      and IgG4 antibodies were not detectable by enzyme-linked immunosorbent assay. BAT
      showed a remarkable increase in the expression of CD203c and CD63 with the
      addition of ginseng extract in a dose-dependent manner, while no changes were
      noted in the controls. In conclusion, oral intake of Korean ginseng could induce
      anaphylaxis, which is mediated by non-IgE-dependent direct activation of
      basophil/mast cells.

PMID- 22379609
TI  - Racialized customer service in restaurants: a quantitative assessment of the
      statistical discrimination explanatory framework.
AB  - Despite popular claims that racism and discrimination are no longer salient
      issues in contemporary society, racial minorities continue to experience
      disparate treatment in everyday public interactions. The context of full-service
      restaurants is one such public setting wherein racial minority patrons, African
      Americans in particular, encounter racial prejudices and discriminate treatment.
      To further understand the causes of such discriminate treatment within the
      restaurant context, this article analyzes primary survey data derived from a
      community sample of servers (N = 200) to assess the explanatory power of one
      posited explanation-statistical discrimination. Taken as a whole, findings
      suggest that while a statistical discrimination framework toward understanding
      variability in servers' discriminatory behaviors should not be disregarded, the
      framework's explanatory utility is limited. Servers' inferences about the
      potential profitability of waiting on customers across racial groups explain
      little of the overall variation in subjects' self-reported discriminatory
      behaviors, thus suggesting that other factors not explored in this research are
      clearly operating and should be the focus of future inquires.

PMID- 22379610
TI  - Grandfather caregivers: race and ethnic differences in poverty.
AB  - We use data from the 2006 American Community Survey to examine race and ethnic
      differences in the effects of marital status and co-residence of the middle
      generation on the likelihood of poverty among grandfathers who have primary
      responsibility for co-resident grandchildren (N = 3,379). Logistic regression
      results indicate that race/ethnicity and household composition are significant
      predictors of poverty for grandfather caregivers: non-Hispanic white
      grandfathers, those who are married, and those with a co-resident middle
      generation are the least likely to be poor. The effects of race/ethnicity,
      marital status, and the presence of a middle generation are, however, contingent
      upon one another. Specifically, the negative effect of being married is lower
      among grandfathers who are Hispanic, African American, non-Hispanic, and non
      Hispanics of other race/ethnic groups compared to whites. In addition, having a
      middle generation in the home has a larger negative effect on poverty for
      race/ethnic minority grandfathers than for non-Hispanic whites. Finally, the
      combined effects of marriage and a middle generation vary across race/ethnic
      group and are associated with lower chances of poverty among some groups compared
      with others. We use the theory of cumulative disadvantage to interpret these
      findings and suggest that race/ethnicity and household composition are
      synergistically related to economic resources for grandfather caregivers.

PMID- 22379611
TI  - Aspects of workplace flexibility and mothers' satisfaction with their husbands'
      contributions to household labor.
AB  - This article explores whether mothers' perceived control over their own workplace
      flexibility options has any relationship to their satisfaction with their
      husbands' contributions to household labor in the United States. We hypothesize
      that flexibility enhances their ability to more adeptly engage in role management
      in multiple life areas, thus enabling them to be more satisfied with their
      partners' domestic input as well. We use a unique data set of 1,078 randomly
      sampled women involved in mothers' organizations that generally attract members
      based on their current level of participation in the paid labor market. We then
      link nine distinct workplace flexibility policies with mothers' satisfaction
      related to their husbands' participation in all household tasks, as well as a
      subset of female-typed tasks. We find that across both arrays of tasks, mothers
      with more perceived control over work-related schedule predictability and those
      that had the ability to secure employment again after an extended break had
      higher levels of satisfaction with their husbands' participation in household
      labor. In addition, short-term time off to address unexpected needs was important
      for all tasks considered together only.

PMID- 22379612
TI  - Measure twice, cut once: achieving consensus on data definitions and quality
      indicators in Canada.

PMID- 22379613
TI  - [Overview of the etiology and course of diarrhea diagnosis in returning
      travelers].

PMID- 22379614
TI  - The brain tumor microenvironment.
AB  - High-grade brain tumors are heterogeneous with respect to the composition of bona
      fide tumor cells and with respect to a range of intermingling parenchymal cells.
      Glioblastomas harbor multiple cell types, some with increased tumorigenicity and
      stem cell-like capacity. The stem-like cells maybe the cells of origin for tumor
      relapse. However, the tumor-associated parenchymal cells such as vascular
      cells,microglia, peripheral immune cells, and neural precursor cells also play a
      vital role in controlling the course of pathology.In this review, we describe the
      multiple interactions of bulk glioma cells and glioma stem cells with parenchymal
      cell populations and highlight the pathological impact as well as signaling
      pathways known for these types of cell-cell communication. The tumor-vasculature
      not only nourishes glioblastomas, but also provides a specialized niche for these
      stem-like cells. In addition, microglial cells,which can contribute up to 30% of
      a brain tumor mass,play a role in glioblastoma cell invasion. Moreover, non
      neoplastic astrocytes can be converted into a reactive phenotype by the glioma
      microenvironment and can then secrete a number of factors which influences tumor
      biology. The young brain may have the capacity to inhibit gliomagenesis by the
      endogenous neural precursor cells, which secrete tumor suppressive factors. The
      factors, pathways, and interactions described in this review provide a new
      prospective on the cell biology of primary brain tumors, which may ultimately
      generate new treatment modalities. However, our picture of the multiple
      interactions between parenchymal and tumor cells is still incomplete.

PMID- 22379616
TI  - Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease.
AB  - PURPOSE: To evaluate the N-acetylaspartate (NAA) and N-acetylaspartylglutamate
      (NAAG) biochemical pathways in the brain of myelin synthesis-deficient (msd)
      mouse, a model of Pelizaeus-Merzbacher disease (PMD). MATERIALS AND METHODS: We
      performed magnetic resonance imaging and proton magnetic resonance spectroscopy
      (1H-MRS) of the thalamus for msd and wildtype mice with a 7.0 T magnet. NAA and
      NAAG were independently measured by high-performance liquid chromatography
      (HPLC). Immunohistochemical analysis using anti-Mbp, Gfap, Ng2, and NeuN
      antibodies were also performed. RESULTS: 1H-MRS in msd mice revealed increased
      total NAA (tNAA, NAApNAAG), creatine, glutamine, and glutamate and decreased
      choline (Cho). HPLC analysis revealed increases of both NAA and NAAG in the msd
      brains. Histologically, the msd brains revealed hypomyelination and astrogliosis.
      Oligodendrocyte progenitor cells and neurons were normal in number in the
      thalamus wherein 1H-MRS was obtained. CONCLUSION: The evidence suggests that the
      neurochemical derangement in the msd mice may be a primary increase of NAA
      resulting in a secondary increase of NAAG. Increased tNAA with decreased Cho
      detectable on 1H-MRS may be an important marker for PMD, and might be used to
      distinguish it from more common neurological disorders that have decreased tNAA.

PMID- 22379617
TI  - Priscilla Maltby Mayden, AHIP, FMLA, 1918-2011.

PMID- 22379618
TI  - [Current Topics in Cardiology in 2011. Introduction: developments in 2011].

PMID- 22379615
TI  - Cthrc1 is a negative regulator of myelination in Schwann cells.
AB  - The analysis of the molecular mechanisms involved in the initial interaction
      between neurons and Schwann cells is a key issue in understanding the myelination
      process. We recently identified Cthrc1 (Collagen triple helix repeat containing
      1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1
      encodes a secreted protein previously shown to be involved in migration and
      proliferation in different cell types. We performed a functional analysis of
      Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA
      interference knockdown in cell culture and a transgenic mouse line that
      overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell
      proliferation but prevents myelination. In particular, time-course analysis of
      myelin formation intransgenic animals reveals that overexpression of Cthrc1 in
      Schwann cells leads to a delay in myelin formation with cells maintaining a
      proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a
      negative regulatory role, fine-tuning the onset of peripheral myelination.

PMID- 22379619
TI  - Subretinal neovascularization following argon laser photocoagulation treatment
      for central serous chorioretinopathy: complication or misdiagnosis? 1975.
AB  - The diagnosis of central serous chorioretinopathy is usually confirmed by the
      fluorescein angiographic finding of one or more pinpoint pigment epithelial leaks
      in or near a macula with a detached sensory retina. When argon laser
      photocoagulation is used to treat pigment epithelial leaks, resolution of the
      leaks occurs with reattachment of the sensory retina. We have seen six patients
      for whom a diagnosis of central serous chorioretinopathy was made; argon laser
      photocoagulation was carried out and subsequently followed by postoperative
      subretinal neovascularization often accompanied by hemorrhage, exudate and, in
      some cases, progressive reduction in visual acuity. Since the presentation of
      this paper to the American Academy of Ophthalmology and Otolaryngology in 1975,
      we have received photographs and case reports of 21 additional patients. This
      paper discusses these 27 cases and demonstrates the causes of the postoperative
      development of subretinal neovascularization

PMID- 22379620
TI  - A 6-year-old girl with progressive ataxia.

PMID- 22379621
TI  - A cervical incidentaloma.

PMID- 22379622
TI  - Glucocorticosteroid-resistant pemphigoid gestationis: successful treatment with
      adjuvant immunoadsorption.
AB  - A 40-year old prima para presented with multiple urticaria-like plaques and
      severe pruritus 2 weeks prior to giving birth by cesarean section. Three days
      after birth, the disease flared up and tense blisters appeared on hands, lower
      arms and feet. Based on the clinical presentation, direct immunofluorescence
      microscopy, complement binding test and detection of high levels of circulating
      anti-BP180 antibodies, the diagnosis of pemphigoid gestationis was established.
      Despite treatment with class IV topical corticosteroid and prednisolone p.o. up
      to 60 mg/day, both skin lesions and severe pruritus progressed accompanied by
      increasing anti-BP180 antibody serum levels. In order to continue breast feeding,
      the prednisolone dose could not be further increased and 10 immunoadsorptions
      over 4 weeks were performed. During this period, skin lesions cleared rapidly,
      pruritus subsided and BP180-specific serum autoantibodies decreased by 99.5%
      allowing the reduction of prednisolone to 7.5 mg/day. We conclude that
      immunoadsorption is an effective and safe adjuvant therapeutic option for severe
      pemphigoid gestationis.

PMID- 22379623
TI  - To use or not to use: Expanding the view on non-addictive psychoactive drug
      consumption and its implications.
AB  - Proposing a change to the view on psychoactive drug use in non-addicts touches a
      sensitive issue because of its potential implications to addiction prevention,
      therapeutic practice, and drug policy. Commentators raised nine questions that
      ranged from clarifications, suggested extensions of the model to supporting data
      previously not regarded, to assumptions on the implications of the model. Here,
      we take up the suggestions of the commentators to expand the model to behavioral
      addictions, discuss additional instrumentalization goals, and review the evidence
      from laboratory animal studies on drug instrumentalization. We consider further
      the role of sociocultural factors and individual development in the establishment
      in drug instrumentalization and addiction. Finally, we clarify which implications
      we think this model may have. We conclude that drug instrumentalization theory
      can be further applied to other behaviors but will require a sensitive debate
      when used for drug and addiction policy that directly affects prevention and
      treatment.

PMID- 22379624
TI  - Role of Hayman technique and its modification in recurrent puerperal uterine
      inversion.
AB  - Acute puerperal uterine inversion is a rare and fatal complication after
      delivery. The first priority is its rapid management and prevention of postpartum
      hemorrhage. On rare occasions, there may be recurrence of inversion after
      reduction. We applied Hayman technique to two cases of recurrent uterine
      inversion.

PMID- 22379625
TI  - Treating co-occurring first-episode psychosis and  borderline personality: a
      pilot randomized  controlled trial.
AB  - AIM: First-episode psychosis and borderline personality disorder are severe
      mental disorders that have their onset in youth. Their co-occurrence is
      clinically well recognized, is associated with significant risks and is complex
      to treat. Yet, there is no published specific intervention for this problem. This
      study reports a pilot randomized controlled trial comparing combined specialist
      first-episode treatment plus specialist early intervention for borderline
      personality, entitled Helping Young People Early, with specialist first-episode
      treatment alone. We aimed to evaluate the safety and feasibility of adding early
      intervention for borderline personality. METHODS: The study investigated the
      safety of specialist first-episode treatment plus specialist early intervention
      for borderline personality in relation to deterioration in psychosis, aggression,
      self-harm and suicidality, and feasibility in relation to the completion of
      therapy phases. Sixteen patients meeting Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for first
      episode psychosis and borderline personality (four or more DSM-IV criteria) were
      randomized either to specialist first-episode treatment alone or specialist first
      episode treatment plus specialist early intervention for borderline personality
      and were followed up at the end of treatment and 6 months later. RESULTS: The
      results showed that it was feasible to recruit and assess a high risk and complex
      group of patients who were agreeable to study participation. Specialist first
      episode treatment plus specialist early intervention for borderline personality
      was an acceptable and safe treatment. CONCLUSION: A larger-scale randomized
      controlled trial of early intervention for borderline personality for young first
      episode psychosis patients with co-occurring full or subsyndromal borderline
      personality is warranted.

PMID- 22379627
TI  - What are the pros and cons of outsourcing our billing operations?

PMID- 22379626
TI  - Blood management: reducing blood use reduces risks and lowers costs.

PMID- 22379628
TI  - Do you use Facebook or Twitter?

PMID- 22379629
TI  - MGMA comments on proposed 2012 Medicare physician fee schedule.

PMID- 22379631
TI  - Treat inmates in your office?

PMID- 22379630
TI  - Meaningful use, RAC audits, Version 5010 and more.

PMID- 22379632
TI  - MGMA calls "accounting of disclosures" proposal unworkable, urges HHS to withdraw
      proposal.

PMID- 22379633
TI  - MGMA asks CMS to revise flawed e-prescribing penalty process.

PMID- 22379660
TI  - Predictive and prognostic markers in cancer.

PMID- 22379661
TI  - Treatment of chemotherapy- induced anemia.

PMID- 22379662
TI  - Hypomethylating agents in myelodysplastic syndromes.

PMID- 22379663
TI  - mTOR inhibitors in sarcoma.

PMID- 22379664
TI  - Letter from the editor: the Big Bang theory.

PMID- 22379665
TI  - Clinical roundtable monograph. Early death in patients with acute promyelocytic
      leukemia.
AB  - With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide,
      acute promyelocytic leukemia (APL) has become a highly curable malignancy.
      Approximately 90% of patients achieve complete remission with induction, which
      generally includes ATRA and an anthracycline-based chemotherapy. Early death,
      either before treatment is initiated or during induction, has emerged as one of
      the most critical issues involved in the current care of patients with APL. The
      main cause of early death in APL is bleeding, often intracranial. It has become
      increasingly clear that induction therapy should be initiated in patients at the
      earliest time possible, even before confirmation of the diagnosis of APL has been
      made. In this roundtable, several experts discuss important insights into the
      high rate of early death observed in APL. In addition to the importance of rapid
      diagnosis, the pathophysiology of the coagulopathy associated with APL will be
      discussed, as will factors that may be predictive of early death and potential
      interventions to prevent this important limitation to the cure of many, if not
      most, patients.

PMID- 22379666
TI  - Brightly photoluminescent phosphor materials based on silicon quantum dots with
      oxide shell passivation.
AB  - We demonstrate silicon-based phosphor materials which exhibit bright
      photoluminescence from near-infra-red to green. The colloidal composites which
      are composed of silicon quantum dots (SiQDs) attached on micro-size silicon
      particles are synthesized by electrochemical etching of silicon wafers and then
      dispersed in ethanol. Subsequently, isotropic etching by HF/HNO3 mixture controls
      the size so as the emission wavelength of SiQDs, and forms an oxide passivating
      shell. The phosphors can further react with alkoxysilanes to form a stable
      suspension in non-polar solvents for solution-processing. The resulting red-light
      emitting SiQD-based phosphors in chloroform exhibit photoluminescence external
      quantum efficiency of 15.9%. Their thin films can be efficiently excited by InGaN
      light-emitting diodes and are stable in room condition.

PMID- 22379667
TI  - TIR RXI collimator.
AB  - A metal-less RXI collimator has been designed using the Simultaneous multiple
      surface method (SMS). Unlike conventional RXI collimators, whose back surface and
      parts of the front surface have to be metalized, this collimator is completely
      metal-free, made only of plastic (PMMA). The collimator's back surface is
      designed as a grooved surface providing two TIR reflections for all rays
      impinging on it. One advantage of the design is the lower manufacturing cost,
      since there is no need for the expensive process of metalization. More
      importantly, unlike conventional RXI collimators, this design performs good
      colour mixing, as well as being very insensitive to the source non-uniformities.
      The experimental measurements of the first prototype show good agreement with the
      simulated design.

PMID- 22379668
TI  - LED backlight designs with the flow-line method.
AB  - An LED backlight has been designed using the flow-line design method. This method
      allows a very efficient control of the light extraction. The light is confined
      inside the guide by total internal reflection, being extracted only by specially
      calculated surfaces: the ejectors. Backlight designs presented here have a total
      optical efficiency of up to 80% (including Fresnel and absorption losses) with an
      FWHM below 30 degrees. The experimental results of the first prototype are shown.

PMID- 22379669
TI  - Highly-efficient, tunable green, phosphor-converted LEDs using a long-pass
      dichroic filter and a series of orthosilicate phosphors for tri-color white LEDs.
AB  - This study introduces a long-pass dichroic filter (LPDF) on top of a phosphor
      converted LED (pc-LED) packing associated with each corresponding tunable
      orthosilicate ((Ba,Sr)2SiO4:Eu) phosphor in order to fabricate tunable green pc
      LEDs. These LPDF-capped green pc-LEDs provide luminous efficacies between 143-173
      lm/W at 60 mA in a wavelength range between 515 and 560 nm. These tunable green
      pc-LEDs can replace green semiconductor-type III-V LEDs, which present challenges
      with respect to generating high luminous efficacy. We also introduce the highly
      efficient tunable green pc-LEDs into tri-color white LED systems that combine an
      InGaN blue LED and green/red full down-converted pc-LEDs. The effect of peak
      wavelength in the tunable green pc-LEDs on the optical properties of a tri-color
      package white LED is analyzed to determine the proper wavelength of green color
      for tri-color white LEDs. The tri-color white LED provides excellent luminous
      efficacy (81.5-109 lm/W) and a good color rendering index (64-87) at 6500 K of
      correlated color temperature (CCT) with the peak wavelength of green pc-LEDs. The
      luminous efficacy of the LPDF-capped green monochromatic pc-LED and tri-color
      package with tunable green pc-LEDs can be increased by improving the external
      quantum efficiency of blue LEDs and the conversion efficiency of green pc-LEDs.

PMID- 22379670
TI  - High efficiency white LEDs with single-crystal ZnO current spreading layers
      deposited by aqueous solution epitaxy.
AB  - Heteroepitaxial ZnO transparent current spreading layers with low sheet
      resistances were deposited on GaN-based light emitting diodes using aqueous
      solution phase epitaxy at temperatures below 90 degrees C. The performance of the
      LEDs was analyzed and compared to identical devices using electron-beam
      evaporated indium tin oxide transparent current spreading layers. White LEDs with
      ZnO layers provided high luminous efficacy-157 lm/W at 0.5A/cm2, and 84.8 lm/W at
      35A/cm2, 24% and 50% higher, respectively, than devices with ITO layers. The
      improvement appears to be due to the enhanced current spreading and low optical
      absorption provided by the ZnO.

PMID- 22379671
TI  - Collimating lamp with well color mixing of red/green/blue LEDs.
AB  - A novel light luminaire is proposed and experimentally analyzed, which
      efficiently mixes and projects the tunable light from red, green and blue (RGB)
      light-emitting diodes (LEDs). Simultaneous light collimation and color mixing is
      a challenging task because most collimators separate colors, and most color
      mixers spread the light beam. Our method is simple and compact; it only uses a
      short light pipe, a thin diffuser, and a total internal reflection lens. We
      performed an experimental study to find a balance between optical efficiency and
      color uniformity by changing light recycling and color mixing.

PMID- 22379672
TI  - Vertical InGaN light-emitting diodes with a sapphire-face-up structure.
AB  - Vertical GaN-based light-emitting diodes (LEDs) were fabricated with a Si
      substrate using the wafer-bonding technique. Lapping and dry-etching processes
      were performed for thinning the sapphire substrate instead of removing this
      substrate using the laser lift-off technique and the thinning process associated
      with the wafer-bonding technique to feature LEDs with a sapphire-face-up
      structure and vertical conduction property. Compared with conventional lateral
      GaN/sapphire-based LEDs, GaN/Si-based vertical LEDs exhibit higher light output
      power and less power degradation at a high driving current, which could be
      attributed to the fact that vertical LEDs behave in a manner similar to flip-chip
      GaN/sapphire LEDs with excellent heat conduction. In addition, with an injection
      current of 350 mA, the output power (or forward voltage) of fabricated vertical
      LEDs can be enhanced (or reduced) by a magnitude of 60% (or 5%) compared with
      conventional GaN/sapphire-based LEDs.

PMID- 22379673
TI  - Performance enhancement of blue light-emitting diodes without an electron
      blocking layer by using special designed p-type doped InGaN barriers.
AB  - In this study, the characteristics of the nitride-based blue light-emitting diode
      (LED) without an electron-blocking layer (EBL) are analyzed numerically. The
      emission spectra, carrier concentrations in the quantum wells (QWs), energy band
      diagrams, electrostatic fields, and internal quantum efficiency (IQE) are
      investigated. The simulation results indicate that the LED without an EBL has a
      better hole-injection efficiency and smaller electrostatic fields in its active
      region over the conventional LED with an AlGaN EBL. The simulation results also
      show that the LED without an EBL has severe efficiency droop. However, when the
      special designed p-type doped InGaN QW barriers are used, the efficiency droop is
      markedly improved and the electroluminescence (EL) emission intensity is greatly
      enhanced which is due to the improvement of the hole uniformity in the active
      region and small electron leakage.

PMID- 22379674
TI  - Periodic Si nanopillar arrays by anodic aluminum oxide template and catalytic
      etching for broadband and omnidirectional light harvesting.
AB  - Large-area, periodic Si nanopillar arrays (NPAs) with the periodicity of 100 nm
      and the diameter of 60 nm were fabricated by metal-assisted chemical etching with
      anodic aluminum oxide as a patterning mask. The 100-nm-periodicity NPAs serve an
      antireflection function especially at the wavelengths of 200~400 nm, where the
      reflectance is decreased to be almost tenth of the value of the polished Si (from
      62.9% to 7.9%). These NPAs show very low reflectance for broadband wavelengths
      and omnidirectional light incidence, attributed to the small periodicity and the
      stepped refractive index of NPA layers. The experimental results are confirmed by
      theoretical calculations. Raman scattering intensity was also found to be
      significantly increased with Si NPAs. The introduction of this industrial-scale
      self-assembly methodology for light

PMID- 22379675
TI  - Light trapping by backside diffraction gratings in silicon solar cells revisited.
AB  - This numerical study investigates the influence of rectangular backside
      diffraction gratings on the efficiency of silicon solar cells. Backside gratings
      are used to diffract incident light to large propagation angles beyond the angle
      of total internal reflection, which can significantly increase the interaction
      length of long wavelength photons inside the silicon layer and thus enhance the
      efficiency. We investigate the influence of the silicon thickness on the optimum
      grating period and modulation depth by a simulation method which combines a 2D
      ray tracing algorithm with rigorous coupled wave analysis (RCWA) for calculating
      the grating diffraction efficiencies. The optimization was performed for gratings
      with period lengths ranging from 0.25 um to 1.5 um and modulation depths ranging
      from 25 nm to 400 nm under the assumption of normal light incidence. This study
      shows that the achievable efficiency improvement of silicon solar cells by means
      of backside diffraction gratings strongly depends on the proper choice of the
      grating parameters for a given silicon thickness. The relationship between the
      optimized grating parameters resulting in maximum photocurrent densities and the
      silicon thickness is determined. Moreover, the thicknesses of silicon solar cells
      with and without optimized backside diffraction gratings providing the same
      photocurrent densities are compared.

PMID- 22379676
TI  - A solar photovoltaic system with ideal efficiency close to the theoretical limit.
AB  - In order to overcome some physical limits, a solar system consisting of five
      single-junction photocells with four optical filters is studied. The four filters
      divide the solar spectrum into five spectral regions. Each single-junction
      photocell with the highest photovoltaic efficiency in a narrower spectral region
      is chosen to optimally fit into the bandwidth of that spectral region. Under the
      condition of solar radiation ranging from 2.4 SUN to 3.8 SUN (AM1.5G), the
      measured peak efficiency under 2.8 SUN radiation reaches about 35.6%,
      corresponding to an ideal efficiency of about 42.7%, achieved for the photocell
      system with a perfect diode structure. Based on the detailed-balance model, the
      calculated theoretical efficiency limit for the system consisting of 5 single
      junction photocells can be about 52.9% under 2.8 SUN (AM1.5G) radiation, implying
      that the ratio of the highest photovoltaic conversion efficiency for the ideal
      photodiode structure to the theoretical efficiency limit can reach about 80.7%.
      The results of this work will provide a way to further enhance the photovoltaic
      conversion efficiency for solar cell systems in future applications.

PMID- 22379677
TI  - Comparing plasmonic and dielectric gratings for absorption enhancement in thin
      film organic solar cells.
AB  - We theoretically investigate and compare the influence of square silver gratings
      and one-dimensional photonic crystal (1D PC) based nanostructures on the light
      absorption of organic solar cells with a thin active layer. We show that, by
      integrating the grating inside the active layer, excited localized surface
      plasmon modes may cause strong field enhancement at the interface between the
      grating and the active layer, which results in broadband absorption enhancement
      of up to 23.4%. Apart from using silver gratings, we show that patterning a 1D PC
      on top of the device may also result in a comparable broadband absorption
      enhancement of 18.9%. The enhancement is due to light scattering of the 1D PC,
      coupling the incoming light into 1D PC Bloch and surface plasmon resonance modes.

PMID- 22379678
TI  - Efficiency enhancement of silicon solar cells using a nano-scale honeycomb
      broadband anti-reflection structure.
AB  - This experiment demonstrates the process for manufacturing a ZnO honeycomb sub
      wavelength structure using nanosphere lithography technology exhibiting excellent
      anti-reflection properties from the UV to NIR wavelength regions. This honeycomb
      nanostructure, combined with commercially available crystalline Si solar cells,
      show substantially improved conversion efficiency from 15.6% to 16.6% using
      optimized honeycomb sizes and precursor concentrations of ZnO. The present work
      develops an unsophisticated and economical technique suitable for industrial
      applications in producing a uniform and low-reflective texture.

PMID- 22379679
TI  - Effect of aperiodicity on the broadband reflection of silicon nanorod structures
      for photovoltaics.
AB  - We carry out a systematic numerical study of the effects of aperiodicity on
      silicon nanorod anti-reflection structures. We use the scattering matrix method
      to calculate the average reflection loss over the solar spectrum for periodic and
      aperiodic arrangements of nanorods. We find that aperiodicity can either improve
      or deteriorate the anti-reflection performance, depending on the nanorod
      diameter. We use a guided random-walk algorithm to design optimal aperiodic
      structures that exhibit lower reflection loss than both optimal periodic and
      random aperiodic structures.

PMID- 22379680
TI  - Surface plasmon effects in the absorption enhancements of amorphous silicon solar
      cells with periodical metal nanowall and nanopillar structures.
AB  - The authors numerically investigate the absorption enhancement of an amorphous Si
      solar cell, in which a periodical one-dimensional nanowall or two-dimensional
      nanopillar structure of the Ag back-reflector is fabricated such that a dome
      shaped grating geometry is formed after Si deposition and indium-tin-oxide
      coating. In this investigation, the effects of surface plasmon (SP) interaction
      in such a metal nanostructure are of major concern. Absorption enhancement in
      most of the solar spectral range of significant amorphous Si absorption (320-800
      nm) is observed in a grating solar cell. In the short-wavelength range of high
      amorphous Si absorption, the weakly wavelength-dependent absorption enhancement
      is mainly caused by the broadband anti-reflection effect, which is produced
      through the surface nano-grating structures. In the long-wavelength range of
      diminishing amorphous Si absorption, the highly wavelength-sensitive absorption
      enhancement is mainly caused by Fabry-Perot resonance and SP interaction. The SP
      interaction includes the contributions of surface plasmon polariton and localized
      surface plasmon.

PMID- 22379682
TI  - Reflection, resolutions  and renewal.

PMID- 22379681
TI  - Transmission line equivalent circuit model applied to a plasmonic grating
      nanosurface for light trapping.
AB  - In this paper, we show how light absorption in a plasmonic grating nanosurface
      can be calculated by means of a simple, analytical model based on a transmission
      line equivalent circuit. The nanosurface is a one-dimensional grating etched into
      a silver metal film covered by a silicon slab. The transmission line model is
      specified for both transverse electric and transverse magnetic polarizations of
      the incident light, and it incorporates the effect of the plasmonic modes
      diffracted by the ridges of the grating. Under the assumption that the adjacent
      ridges are weakly interacting in terms of diffracted waves, we show that the
      approximate, closed form expression for the reflection coefficient at the air
      silicon interface can be used to evaluate light absorption of the solar cell. The
      weak-coupling assumption is valid if the grating structure is not closely packed
      and the excitation direction is close to normal incidence. Also, we show the
      utility of the circuit theory for understanding how the peaks in the absorption
      coefficient are related to the resonances of the equivalent transmission model
      and how this can help in designing more efficient structures.

PMID- 22379683
TI  - Forms of address between  patients and GPs.

PMID- 22379684
TI  - Group health plans and health insurance issuers relating to coverage of
      preventive services under the Patient Protection and Affordable Care Act. Final
      rules.
AB  - These regulations finalize, without change, interim final regulations authorizing
      the exemption of group health plans and group health insurance coverage sponsored
      by certain religious employers from having to cover certain preventive health
      services under provisions of the Patient Protection and Affordable Care Act.

PMID- 22379685
TI  - International Conference on Harmonisation; Guidance on E7 Studies in Support of
      Special Populations; Geriatrics; Questions and Answers; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled ''E7 Studies in Support of Special Populations: Geriatrics;
      Questions and Answers.'' The guidance was prepared under the auspices of the
      International Conference on Harmonisation of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH). The questions and answers
      (Q&A) guidance addresses special considerations for the design and conduct of
      clinical trials of drugs likely to have significant use in the elderly. The Q&As
      are intended to provide guidance on the use of geriatric data to adequately
      characterize and represent the safety and efficacy of a drug for a marketing
      application, including data collected postmarketing.

PMID- 22379686
TI  - How we collect and consider evidence of disability. Final rule.
AB  - We are modifying the requirement to recontact your medical source(s) first when
      we need to resolve an inconsistency or insufficiency in the evidence he or she
      provided. Depending on the nature of the inconsistency or insufficiency, there
      may be other, more appropriate sources from whom we could obtain the information
      we need. By giving adjudicators more flexibility in determining how best to
      obtain this information, we will be able to make a determination or decision on
      disability claims more quickly and efficiently in certain situations. Eventually,
      our need to recontact your medical source(s) in many situations will be
      significantly reduced as a result of our efforts to improve the evidence
      collection process through the increased use of Health Information Technology
      (HIT).

PMID- 22379687
TI  - Protecting the public and our employees in our hearing process. Final rule.
AB  - We are clarifying our regulations to ensure the safety of the public and our
      employees in our hearing process. Due to increasing reports of threats to our
      hearing office employees, we are taking steps to explicitly increase the level of
      protection we provide to our staff and to the public during the hearing process.
      We expect these changes to result in a safer work environment for our employees,
      while at the same time ensuring that our claimants continue to receive a full and
      fair hearing on their claims for benefits.

PMID- 22379688
TI  - Establishment, maintenance, and availability of records: amendment to record
      availability requirements. Interim final rule; request for comments.
AB  - The Food and Drug Administration (FDA) is amending its regulations on
      establishment, maintenance, and availability of records. FDA is issuing this
      interim final rule (IFR) to amend FDA's regulation on the record availability
      requirements to implement the amendments to the Federal Food, Drug, and Cosmetic
      Act (the FD&C Act) made by the FDA Food Safety Modernization Act (FSMA). The FSMA
      amendment expands FDA's former records access authority beyond records relating
      to the specific suspect article of food to records relating to any other article
      of food that the Secretary of Health and Human Services (the Secretary)
      reasonably believes is likely to be affected in a similar manner. In addition,
      the FSMA amendment permits FDA to access records relating to articles of food for
      which the Secretary believes that there is a reasonable probability that the use
      of or exposure to the article of food, and any other article of food that the
      Secretary reasonably believes is likely to be affected in a similar manner, will
      cause serious adverse health consequences or death to humans or animals. This
      expanded records access authority will further help improve FDA's ability to
      respond to, and further contain threats of serious adverse health consequences or
      death to humans or animals.

PMID- 22379689
TI  - International Conference on Harmonisation; final recommendation for the revision
      of the permitted daily exposure for the solvent cumene according to the
      maintenance procedures for the guidance Q3C Impurities: Residual Solvents;
      availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a final
      recommendation for the revision of the permitted daily exposure (PDE) for the
      solvent cumene according to the maintenance procedures for the guidance for
      industry entitled ''Q3C Impurities: Residual Solvents.'' The recommendation was
      prepared under the auspices of the International Conference on Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

PMID- 22379690
TI  - Medicaid program; review and approval process for Section 1115 demonstrations.
      Final rule.
AB  - This final rule will implement provisions of section 10201(i) of the Patient
      Protection and Affordable Care Act of 2010 that set forth transparency and public
      notice procedures for experimental, pilot, and demonstration projects approved
      under section 1115 of the Social Security Act relating to Medicaid and the
      Children's Health Insurance Program (CHIP). This final rule will increase the
      degree to which information about Medicaid and CHIP demonstration applications
      and approved demonstration projects is publicly available and promote greater
      transparency in the review and approval of demonstrations. It will also codify
      existing statutory requirements pertaining to seeking advice from Indian health
      care providers and urban Indian organizations for section 1115 demonstration
      projects, and for the first time impose as regulatory requirements tribal
      consultation standards that were previously only published as guidance documents.

PMID- 22379691
TI  - Application, review, and reporting process for Waivers for State Innovation.
      Final rule.
AB  - This final rule sets forth a procedural framework for submission and review of
      initial applications for a Waiver for State Innovation described in section 1332
      of the Patient Protection and the Affordable Care Act including processes to
      ensure opportunities for public input in the development of such applications by
      States and in the Federal review of the applications.

PMID- 22379692
TI  - The role of spatial switching in the attentional blink.
AB  - The attentional blink (AB) is a well-established paradigm in which identification
      of a target T2 is reduced shortly after presentation of an earlier target T1. An
      important question concerns the importance of backward masking during the AB.
      While task switching has been found to be a strong modulator mediating the AB
      without any masking of T2, the present study investigated whether spatial
      switching could similarly produce an AB without masking. Using a spatial AB
      paradigm in which items appeared at different locations; we found (a) a
      significant AB without backward masking of T2 but no AB when no distractors
      followed T2, (b) no evidence for Lag 1 sparing. These findings show that when
      there is a spatial switch between the targets, presenting the distractor
      following T2 at the same location than T2 (backward masking) is not a necessary
      condition for the AB to occur, but T2 has to be followed by surrounding
      distractors (appearing at different locations than T2). This pattern of data
      confirms that spatial switching is a robust modulator of the AB, but to a less
      extent than task switching.

PMID- 22379693
TI  - Mechanisms of contextual control when contexts are informative to solve the task.
AB  - An experiment was conducted using a human instrumental learning task with the
      goal of evaluating the mechanisms underlying the deleterious effect of context
      switching on responding to an unambiguous stimulus when contexts are informative
      to solve the task. Participants were trained in a context-based reversal
      discrimination in which two discriminative stimuli (X and Y) interchange their
      meaning across contexts A and B. In context A, discriminative stimulus Z
      consistently announced that the relationship between a specific instrumental
      response (RI) and a specific outcome (O1) was in effect. Performance in the
      presence of stimulus Z was equally deteriorated when the test was conducted
      outside the training context, regardless of whether the test context was familiar
      (context B) or new (context C). This result is consistent with the idea that
      participants code all the information presented in an informative context as
      context-specific with the context playing a role akin to an occasion setter.

PMID- 22379694
TI  - Age differences in source monitoring and referent discrimination.
AB  - In contrast to previous studies which addressed separately memory for source and
      referent, the present experiment analyzes the effects of aging on memory for
      both, source and referent. The experiment simulated a conversation between two
      people exchanging descriptors of themselves and the other speaker (e.g., "I am
      helpful," "you are capable"). Participants (N = 60) were divided into two age
      groups: younger (M = 23.47 years old, SD = 2.37), older (M = 70.30 years old, SD
      = 3.73). Recall, recognition, and accuracy in identifying source (e.g., "who said
      helpful?") and referent (e.g., "about whom was capable said?") were analyzed.
      Younger and older adults recalled and recognized equally well information read by
      the experimenter about herself, but only young adults showed better memory for
      the descriptors they read about themselves. Older adults were impaired in source
      monitoring, but not in reference discrimination. Normal referent discrimination
      in older adults is attributed to the fact that the referent forms part of the
      content of the episode, whereas who spoke it is part of its context, and older
      adults tend to show greater deficits in context than in content memory. These
      results are explained within the source and reality monitoring framework.

PMID- 22379695
TI  - Relationship between physical prowess and cognitive function.
AB  - There is some evidence about the low relationship between physical prowess and
      cognitive function (Posthuma, Mulder, Boomsma & de Geus, 2002). The aim of this
      paper is to investigate the relationship between cognitive variables (spatial
      ability, reasoning, numerical ability, inductive reasoning, and reasoning and
      verbal comprehension) and physical prowess in sport performance (agility circuit,
      coordination circuit, horizontal jump, swimming and sprint racing). Two studies
      were performance. In the first one we applied a battery of standardized cognitive
      tests and a battery of physical grading tests to 400 subjects. When we applied
      factor analysis to the physical prowess and the cognitive variables, we found one
      general factor in cognitive variables and one general factor in physical prowess.
      We found a low relationship between both factors (.21). In the second study we
      compare the cognitive abilities in elite and amateur sport people. Results show
      that elite gymnastics people present higher cognitive abilities than amateur
      sportspeople. It should be relevant in order to clarify the total set of
      variables involved in sport performance.

PMID- 22379696
TI  - Processing of Spanish Preterite regular and irregular verbs: the role of
      neighborhood density.
AB  - Research into lexical processes shows that frequency and phonological similarity
      (neighborhood density) affect word processing and retrieval. Previous studies on
      inflectional morphology have examined the influence of frequency of occurrence in
      speech production on the inflectional verb paradigm in English. Limited work has
      been done to examine the influence of phonological similarity in languages with a
      more complex morphological system than English. The present study examined the
      influence of neighborhood density on the processing of Spanish Preterite regular
      and irregular verbs as produced by thirty native speakers of Spanish. The results
      of a naming task showed that regular verbs were processed faster and more
      accurately than irregular ones. Similar to what has been observed in English, a
      facilitative effect of neighborhood density for -ir verbs was observed in both
      regular and irregular verbs, such that -ir verbs with dense neighborhoods were
      produced faster and more accurately than -ir verbs with sparse neighborhoods.
      However, no neighborhood density effects were observed for -ar verbs (regular and
      irregular) in reaction times and accuracy rates. Thus, the activation of a
      specific -ir verb was facilitated by similar sounding verbs regardless of being
      regular and irregular. Implications for models of morphology language processing
      are discussed.

PMID- 22379697
TI  - An explanatory model of academic achievement based on aptitudes, goal
      orientations, self-concept and learning strategies.
AB  - As a result of studies examining factors involved in the learning process,
      various structural models have been developed to explain the direct and indirect
      effects that occur between the variables in these models. The objective was to
      evaluate a structural model of cognitive and motivational variables predicting
      academic achievement, including general intelligence, academic self-concept, goal
      orientations, effort and learning strategies. The sample comprised of 341 Spanish
      students in the first year of compulsory secondary education. Different tests and
      questionnaires were used to evaluate each variable, and Structural Equation
      Modelling (SEM) was applied to contrast the relationships of the initial model.
      The model proposed had a satisfactory fit, and all the hypothesised relationships
      were significant. General intelligence was the variable most able to explain
      academic achievement. Also important was the direct influence of academic self
      concept on achievement, goal orientations and effort, as well as the mediating
      ability of effort and learning strategies between academic goals and final
      achievement.

PMID- 22379698
TI  - Differences between immigrant and national students in motivational variables and
      classroom-motivational-climate perception.
AB  - The objective of this study is to see whether Immigrant (IM) and Spanish
      (National) students (SP) need different kinds of help from teachers due to
      differences in motivation, family expectancies and interests and classroom
      motivational-climate perception. A sample of Secondary Students -242 Spanish and
      243 Immigrants- completed questionnaires assessing goal orientations and
      expectancies, family attitudes towards academic work, perception of classroom
      motivational climate and of its effects, satisfaction, disruptive behavior and
      achievement. ANOVAs showed differences in many of the motivational variables
      assessed as well as in family attitudes. In most cases, Immigrant students scored
      lower than Spanish students in the relevant variables. Regression analyses showed
      that personal and family differences were related to student's satisfaction,
      achievement and disruptive behavior. Finally, multi-group analysis of classroom
      motivational-climate (CMC) showed similarities and differences in the
      motivational value attributed by IM and SP to each specific teaching pattern that
      configure the CMC. IM lower self-esteem could explain these results, whose
      implications for teaching and research are discussed.

PMID- 22379699
TI  - Prospective teachers' conceptions of assessment: a cross-cultural comparison.
AB  - This paper examines the responses of two sample of prospective teachers (New
      Zealand, n = 324; and Spain, n = 672) to the Teachers' Conceptions of Assessment
      inventory (English and Spanish respectively). The inventory captures four major
      intentions for assessment (i.e., improvement, irrelevance, school and student
      accountability). The conceptions of prospective teachers about the nature and
      purpose of assessment are relevant, given that (a) much educational assessment is
      carried out in classrooms; and (b) prospective teachers enter the teacher
      education programs with significant prior school experience of assessment as
      pupils. Results of confirmatory factor analysis indicated that the original model
      was inadmissible and that the best-fitting revised model was only configurally
      invariant between the two samples. It would appear that lack of teaching
      experience results in different responses for prospective teachers to those of
      practicing teachers. Moreover, differences in societal and cultural priorities
      for assessment use most likely explain the lack of invariance between samples.

PMID- 22379700
TI  - Prediction of adolescents doing physical activity after completing secondary
      education.
AB  - The purpose of this study, based on the self-determination theory (Ryan & Deci,
      2000) was to test the prediction power of student's responsibility, psychological
      mediators, intrinsic motivation and the importance attached to physical education
      in the intention to continue to practice some form of physical activity and/or
      sport, and the possible relationships that exist between these variables. We used
      a sample of 482 adolescent students in physical education classes, with a mean
      age of 14.3 years, which were measured for responsibility, psychological
      mediators, sports motivation, the importance of physical education and intention
      to be physically active. We completed an analysis of structural equations
      modelling. The results showed that the responsibility positively predicted
      psychological mediators, and this predicted intrinsic motivation, which
      positively predicted the importance students attach to physical education, and
      this, finally, positively predicted the intention of the student to continue
      doing sport. Results are discussed in relation to the promotion of student's
      responsibility towards a greater commitment to the practice of physical exercise.

PMID- 22379701
TI  - Neuropsychological evaluation of high-risk children from birth to seven years of
      age.
AB  - High Risk Children (HRC) are those with an increased risk of abnormal development
      due to any factor affecting neurological growth. Those factors have been the
      focus of most studies in this area. However, little is known about their long
      term consequences over the course of child development. OBJECTIVES: The goal was
      to study the cognitive, emotional and academic outcomes of 7-year-old children
      diagnosed as HRC at birth. METHOD: We compared 14 HRC and 20 healthy children
      using the WISC-IV, BASC and Brunet-Lezine tests. RESULTS: HRC showed cognitive,
      emotional and academic deficits compared with healthy children. However, Brunet
      Lezine scores obtained over the course of development (6, 12, 18 and 24 months)
      were not predictive of the children's' current psychological status. CONCLUSIONS:
      Long-term follow-up with HRC should be maintained until 7 years of age, at which
      point an appropriate treatment should be implemented.

PMID- 22379702
TI  - The relationship between early lexical and grammatical development in Spanish:
      evidence in children with different linguistic levels.
AB  - This study analyzes the relationship between lexical and grammatical development
      in Spanish children. The (European) Spanish version of the MacArthur-Bates CDI
      was used and administered to 593 Spanish-speaking children between the ages of 16
      and 30-months-old. Regression analysis was applied to evaluate the relationship
      between age, vocabulary (total vocabulary, nouns, and verbs) and grammatical
      scores on two subsections of the Grammar Part. Total vocabulary explained a
      significantly greater proportion of variance in grammatical outcomes than age
      did. However, noun and verb vocabularies did not explain a greater proportion of
      variance in their respective morphologies than total vocabulary did.
      Additionally, the predictive relationship between vocabulary and grammar was
      found to be weaker for children whose scores were below the 10th percentile,
      although this could be due to the minor variability in this group and to extreme
      cases. We discuss the implications of these results in relation to the question
      of continuity between early vocabulary and grammar development in children.

PMID- 22379703
TI  - Family functioning and socioaffective competencies of children in the beginning
      of schooling.
AB  - The aim of this short-term longitudinal study, based on the system theory, was to
      test the association between different aspects of family functioning of
      preschoolers and their socioaffective competencies at the end of the first grade.
      The total sample included 278 children (137 boys and 141 girls) and their
      families. The analysis of variance results regarding the aspects of family
      cohesion and harmony showed that preschoolers from more cohesive families display
      more social skills, while those from more conflicting families display more
      externalizing behavior problems (aggression and irritability). With respect to
      the family's ability to resolve problems, it was observed that, especially for
      middle and upper class families, this aspect is associated with better social
      skills and fewer internalized behavior problems. Overall, results of the present
      study suggest that the family functioning at early stage might influence
      children's abilities to regulate their emotions and to establish/maintain
      important relationships with peers and teachers in their early school years.

PMID- 22379704
TI  - Parental knowledge and adolescent adjustment: substance use and health-related
      quality of life.
AB  - This study analyses two models (maternal and paternal) in which parental care and
      sources of parental knowledge moderated the relationship between parents'
      knowledge about their adolescents' lives and adolescents' substance use and
      health-related quality of life. The sample was made up of 15942 Spanish
      adolescents who participated in the 2006 edition of Health Behavior in School
      aged Children Study. Results showed that increased parents' knowledge about their
      adolescents' lives reduced adolescents' substance use and increased their quality
      of life. With respect to the moderation relationship, a limited effect was found.
      However, parental care and sources of parental knowledge used by both parents
      generally had main effects on adolescents' substance use and health-related
      quality of life, with care being the most relevant variable in the health-related
      quality of life, while knowledge was the most relevant one for substance use.

PMID- 22379705
TI  - Interparental violence and children's long-term psychosocial adjustment: the
      mediating role of parenting practices.
AB  - The objectives of this study were: (a) to examine the direct and indirect
      relationships among witnessing interparental violence, parenting practices, and
      children's long-term psychosocial adjustment; (b) to analyze the possible gender
      differences in the relationships specified. The sample consisted of 1295 Spanish
      university students (M age = 21.21, SD = 4.04). We performed statistical analyses
      using structural equation modeling. The results showed that witnessing parental
      violence as a child is related to poor long-term psychosocial adjustment during
      the child's adult years. Furthermore, we found that parenting practices fully
      mediated the relation between witnessing interparental violence and the child's
      long-term adjustment. The multigroup analyses showed that most of the relations
      among the variables did not differ significantly by gender. However, the relation
      between harsh discipline and antisocial behavior was stronger for males, whereas
      the relation between harsh discipline and depressive symptoms was stronger for
      females. Finally, we discuss the implications of these findings for the
      clinicians and specialists who plan and develop intervention programs for
      populations at risk.

PMID- 22379706
TI  - An investigation on the mediating role of coping strategies on locus of control--
      wellbeing relationship.
AB  - The relationship among coping strategies, locus of control, and workplace
      wellbeing is examined. The model hypothesizes that coping strategies mediate the
      relationship between locus of control and work place well being. To test the
      model, data was collected from 154 software professionals using separate tools to
      assess coping strategies, locus of control and work place wellbeing. Model fit
      for the collected data was examined using structural equation modeling technique
      with the help of AMOS. Results support the view that coping strategies mediate
      the relationship between locus of control and work place wellbeing. While the
      path between locus of control and wellbeing is significant, the path between
      coping distraction and wellbeing is not significant.

PMID- 22379707
TI  - Correlations between subjective well-being, dyadic adjustment and marital
      satisfaction in Brazilian married people.
AB  - This study aimed to investigate the relationships between the constructs
      subjective well-being (SWB), dyadic adjustment (DA) and marital satisfaction
      (MS). Participants were 106 married Brazilians, of both sexes, with a mean age of
      42 (+/- 11) years. Instruments used for the sociodemographic characterization and
      socioeconomic classification were the Subjective Wellbeing Scale (SWBS), the
      Dyadic Adjustment Scale (DAS) and the Marital Satisfaction Scale (MSS). Through
      the analysis of correlations and of stepwise multiple regression, it was verified
      that all the factors of the dyadic adjustment showed correlation with the marital
      satisfaction. The satisfaction with life (factor of the SWBS) and dyadic
      satisfaction (factor of the DAS), were positively and significantly correlated (r
      = .20: p = .04), which reveals that people who say they are satisfied with life
      in different domains also do so in relation to the marital experience,

PMID- 22379708
TI  - Health-related quality of life in children and adolescents: subjective well
      being.
AB  - The main objective of this study was to build a model, which includes personal
      and social factors, that helps to highlight factors that promote health-related
      quality of Life (HRQoL) in children and in adolescents. A sample of 3195 children
      and adolescents was acquired from 5th and 7th graders from all five Portuguese
      regions. In this study three independent latent variables were specified-
      Physical, Psychological and Social and two dependent latent variables were
      measured: Health behavior and Quality of Life. The integrative model was composed
      by different components: (1) health-related quality of life, integrated by 8
      dimensions from KIDSCREEN-52; (2) health behavior, (3) variables related to
      physical health; (4) variables related to social health; (5) variables related to
      psychological health. As results were found strong correlation between
      psychological dimensions and self-esteem and other factors and a structural
      equation model was developed. The model presented a RMSEA index of .08.
      Similarly, adjustment levels for the CFI, NFI and IFI vary above or around .90,
      which suggests a good adjustment for the hypothesized model. The model presented
      significant qui-square. This study showed that in all the samples studied, the
      psychological variables were those that contributed at a superior level to HRQoL.

PMID- 22379709
TI  - Heterosexual romantic relationships, interpersonal needs, and quality of life in
      prison.
AB  - The purpose of this study was to investigate the moderating effect of having vs.
      not having a and quality of life. In-person interviews were conducted with 55
      male and 64 female inmates from the Topas Penitentiary (Spain). Higher levels of
      social loneliness and lower levels of sexual satisfaction were associated with
      lower levels of quality of life. In addition, the interaction between sexual
      satisfaction and romantic partner status was significant. Higher levels of sexual
      satisfaction were associated with higher levels of quality of life only for the
      group without a partner. These findings support a "bad is stronger than good"
      principle and indicate the detrimental aspects that can be associated with not
      having a satisfactory sexual life while incarcerated.

PMID- 22379710
TI  - Character strengths: a study of Argentinean soldiers.
AB  - The primary objective of this research was to study the differences in positive
      traits between military and civilian college students and between cadets in their
      first and final years at a military academy. Second, the research aimed to study
      the relations between positive traits and the academic and military performance
      of cadets in their first and final years, according to the classification of
      positive traits by Peterson and Seligman (2004). To accomplish these objectives,
      a sample of university students from a military educational institution and a
      sample of civilian university students were studied. The instruments used were a
      24-item self-report measure of positive traits, a measure of social desirability,
      and objective scores of academic and military performance. The results generally
      showed that when age and career stage were held constant, the scores of the
      military students were higher than the scores of the civilian students across
      various strengths. Military students reported higher levels of the character
      strength of spirituality than did civilian students. The relationships between
      strengths and performance differed for students in their first and final years at
      the military academy. In particular, cadets with the higher levels of academic or
      military performance in their last year, i.e., the cadets best adapted to the
      academy, reported higher levels of the character strength of persistence when
      compared to low-performing cadets in the same year of study.

PMID- 22379711
TI  - Human values in the team leader selection process.
AB  - The selection process of team leaders is fundamental if the effectiveness of
      teams is to be guaranteed. Human values have proven to be an important factor in
      the behaviour of individuals and leaders. The aim of this study is twofold. The
      first is to validate Schwartz's survey of human values. The second is to
      determine whether there are any relationships between the values held by
      individuals and their preferred roles in a team. Human values were measured by
      the items of the Schwartz Value Survey (SVS) and the preferred roles in a team
      were identified by the Belbin Self Perception Inventory (BSPI). The two
      questionnaires were answered by two samples of undergraduate students (183 and
      177 students, respectively). As far as the first objective is concerned, Smallest
      Space Analysis (SSA) was performed at the outset to examine how well the two
      dimensional circular structure, as postulated by Schwartz, was represented in the
      study population. Then, the results of this analysis were compared and contrasted
      with those of two other published studies; one by Schwartz (2006) and one by Ros
      and Grad (1991). As for the second objective, Pearson correlation coefficients
      were computed to assess the associations between the ratings on the SVS survey
      items and the ratings on the eight team roles as measured by the BSPI.

PMID- 22379712
TI  - Personality and emotional intelligence in teacher burnout.
AB  - This paper aims to investigate the relationship between teacher's personality
      types, emotional intelligence and burnout and to predict the burnout levels of
      147 teachers in the city of Mashhad (Iran). To this end, we have used three
      inventories: Maslach Burnout Inventory (MBI), NEO Five Factor Inventory (NEO
      FFI), and Emotional Quotient Inventory (EQ-I). We used Homogeneity Analysis and
      Multiple Linear Regression to analyze the data. The results exhibited a
      significant relationship between personality types and emotional intelligence and
      the three dimensions of burnout. It was indicated that the best predictors for
      emotional exhaustion were neuroticism and extroversion, for depersonalization
      were intrapersonal scale of emotional intelligence and agreeableness, and for
      personal accomplishment were interpersonal scale and conscientiousness. Finally,
      the results were discussed in the context of teacher burnout.

PMID- 22379713
TI  - Affiliative stimuli as primers to prosocial predispositions.
AB  - Affiliative stimuli are pleasant and highly biologically relevant. Affiliative
      cues are thought to elicit a prosocial predisposition. Here affiliative and
      neutral pictures were exposed prior to a reaction time task which consisted in
      responding to a visual target. Half the participants responded with finger
      flexion, a movement frequently involved in prosocial activities. The other half
      responded with finger extension, a less prosocially compatible movement. Results
      showed that under the exposure to affiliative pictures, as compared to neutral
      ones, participants who used finger flexion were faster, while those using finger
      extension were slower. Performance benefits to the task, when flexing the finger,
      together with performance costs, when extending it, indicate the relevance of
      movement compatibility to the context. These findings put forward a possible link
      between affiliative primers and motor preparation to facilitate a repertoire of
      movements related to prosocial predispositions including finger flexion.

PMID- 22379714
TI  - Organizational identification and commitment: correlates of sense of belonging
      and affective commitment.
AB  - The general purpose of this work is to analyze the overlap between organizational
      identification and commitment. Specifically, our study focuses on the analysis of
      the differences and similarities between sense of belonging (a dimension of
      organizational identification) and affective commitment (a dimension of
      organizational commitment). In order to do this, we analyzed their discriminant
      validity and raised their relationship with variables that previous research had
      showed like precedent and subsequent variables of them: value congruence,
      perceived support, organizational citizenship behavior, and intention to continue
      in the organization. A total of 292 people at one organization completed surveys
      measuring the variables previously described. The results showed that sense of
      belonging and affective commitment are different concepts and they have different
      relationships with relation to precedent and subsequent variables. Affective
      commitment seems to be more useful than sense of belonging to predict
      organizational citizenship behavior aimed at the organization and intention to
      continue. Some practical implications are described.

PMID- 22379715
TI  - Traits that define the different alcohol intensive consume type during the
      practice of "botellon".
AB  - There is a phenomenon contributing to the current pattern of alcohol consumption
      among youngsters in Spain known as "botellon". From research financed by the
      National Plan on Drugs (2004-2007), data of 6009 youngsters (14-25 years old)
      were collected from three Spanish cities. Only individuals who engage in
      intensive consumption of alcohol (n = 2807) have been included. The purpose of
      this work has been to identify the different types of consumers at risk through a
      cluster analysis and to establish a profile for each particular group. Four
      groups were differentiated by age, gender, alcohol consumption and years of
      consumption. It was observed that adolescent students and university students of
      the same sex consume similar quantities of alcohol, and justify their consumption
      alluding to personal factors, whereas university students refer to issues related
      to control of leisure. The consumption by males is the highest, and they are the
      most likely to seek drunkenness. They associate to a lesser degree their
      consumption with the possibility of developing an addictive process. In general,
      all youngsters consider that their consumption will have no negative
      consequences. These results indicate the need to come up with different
      alternatives, addressing the particularities of each group.

PMID- 22379716
TI  - Aesthetic sports as high-risk contexts for eating disorders--young elite dancers
      and gymnasts perspectives.
AB  - This is the first study developed in Portugal which investigates specific
      characteristics of dance and gymnastics environments that make them high-risk
      contexts for the development of eating disorders. Four focus groups were
      conducted with thirteen ballet students from a professional dance school and nine
      gymnasts from a gymnastics club (aged 12 to 17 years old), which were subjected
      to an inductive-deductive analysis procedure. Specific risk and protective
      factors were identified. Among their respective sources of influence, teachers
      and coaches are those who exert a stronger influence upon young athletes. We also
      explored some themes related to the influence of peers, parents, and
      environmental characteristics, which could have an important role on the
      development or prevention of disordered eating.

PMID- 22379717
TI  - A study of patients who go to a psychology clinic seeking treatment.
AB  - In order to characterize a typical clinical context, as opposed to an academic or
      research context, this article will analyze the sociodemographic and clinical
      characteristics of patients who turn to a psychology clinic in need of
      professional help. This study was conducted using an initial sample of 1,305
      patients at the Universidad Complutense de Madrid (UCM) Clinica Universitaria de
      Psicologia. Of the sociodemographic characteristics studied, it is noteworthy
      that the majority of patients were women (65%) and relatively young (the average
      age is 29.7 years-old). The disorders for which psychological help was most often
      needed were anxiety and mood disorders and relationship problems, which together
      made up 50% of cases. In 17.70% of cases, patients had at least one comorbid
      disorder in addition to the one that brought them to the clinic. The
      generalizability and implications of the results are discussed.

PMID- 22379718
TI  - The role of optimism and pessimism in chronic pain patients adjustment.
AB  - This study analyses the relationships between patients' dispositional optimism
      and pessimism and the coping strategies they use. In addition, the coping
      strategies repercussions on adjustment to chronic pain were studied. Ninety-eight
      patients with heterogeneous chronic pain participated. The assessment tools were
      as follows: Life Orientation Test (LOT), the Vanderbilt Pain Management Inventory
      (VPMI), the McGill Pain Questionnaire (MPQ), Hospital Anxiety and Depression
      Scale (HADS), and the Impairment and Functioning Inventory for Chronic Pain
      Patients (IFI). The hypothetical model establishes positive relationships between
      optimism and the use of active coping strategies, whereas pessimism is related to
      the use of passive coping. Active coping is associated with low levels of pain,
      anxiety, depression and impairment and high levels of functioning. However,
      passive coping is related to high levels of pain, anxiety, depression and
      impairment and low levels of functioning. The hypothetical model was empirically
      tested using the LISREL 8.20 software package and the unweighted least squares
      method. The results support the hypotheses formulated regarding the relations
      among optimism, pessimism, coping and adjust of chronic pain patients. By
      analysing optimism among chronic pain patients, clinicians could make better
      predictions regarding coping and adjustment.

PMID- 22379719
TI  - Coping style and depressive symptomatology during pregnancy in a private setting
      sample.
AB  - AIM: To evaluate the association of antenatal depressive symptomatology (AD) with
      life events and coping styles, the hypothesis was that certain coping strategies
      are associated to depressive symptomatology. METHODS: We performed a cross
      sectional study of 312 women attending a private clinic in the city of Osasco,
      Sao Paulo from 27/05/1998 to 13/05/2002. The following instruments were used:
      Beck Depression Inventory (BDI), Holmes and Rahe Schedule of Recent Events
      (SSRS), Folkman and Lazarus Ways of Coping Questionnaire and questionnaire with
      social-demographic and obstetric data. INCLUSION CRITERIA: women with no past
      history of depression, psychiatric treatment, alcohol or drug abuse and no
      clinical-obstetrical complications. Odds ratios and 95% CI were used to examine
      the association between AD (according to BDI) and exposures variables. Hypothesis
      testing was done with Chi2 tests and ap value < .05. RESULTS: AD occurred in
      21.1% of pregnant women. By the univariate analyses, education, number of
      pregnancies, previous abortion, husband income, situation of marriage and score
      of SSRS were associated with AD. All coping styles were associated with AD,
      except seeking support and positive reappraisal. By the multivariate analyses,
      four coping styles were kept in the final model: confront (p = .039), accepting
      responsibility (p < .001), escape-avoidance (p = .002), problem-solving (p =
      .005). CONCLUSIONS: AD was highly prevalent and was associated with maladaptive
      coping styles.

PMID- 22379720
TI  - Relationship between schizotypal and borderline traits in college students.
AB  - The main objective of the present investigation was to analyze the relationship
      between self-reported schizotypal and borderline personality traits in a sample
      of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the
      Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and
      Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered.
      The results showed that schizotypal and borderline features are partially related
      at subclinical level. The exploratory factor analysis conducted on the subscales
      revealed a three-factor solution comprised of the following factors:
      Identity/Interpersonal, Lack of Control and Schizotypal. The canonical
      correlation analysis showed that schizotypal features and borderline personality
      traits shared 34.8% of the variance. The data highlight the overlap between
      schizotypal and borderline personality traits in nonclinical young adults. Future
      studies should continue to examine the relationship and the degree of overlap
      between these traits in community samples.

PMID- 22379721
TI  - Batterer men in prison and in court-referred treatment programmes: what is the
      difference?
AB  - This paper describes the demographic, gender violence and psychopathological
      characteristics of 399 men in a specialized treatment programme for gender
      violence. Furthermore, a comparison of all the variables studied among the
      subjects referred by the court to the treatment programme (n = 276) and those who
      were imprisoned (n = 123) was conducted. The results showed the existence of
      numerous statistically significant differences between groups, primarily in
      psychopathological variables and in cognitive bias about women and violence use.
      In general, imprisoned batterers showed more irrational beliefs both about women
      and about violence as a strategy to cope with everyday difficulties. Moreover,
      batterers in prison had significantly higher scores on all psychopathological
      symptoms as assessed by SCL-90-R, as well as in most of STAXI-2 subscales.
      According to these results, batterers in prison showed a higher severity in
      variables studied than those who were referred by the court to the treatment
      programme. Implications of these results for further research and clinical
      practice are also commented on.

PMID- 22379722
TI  - Dimensionality and Transcultural Specificity of the Sexual Attraction
      Questionnaire (SAQ).
AB  - Sexual attraction was considered a component of sexual orientation from the
      beginning of the second half of the 20th century to present times. However, some
      recent researchers have studied sexual attraction as an independent field
      measuring it by the Sexual Attraction Questionnaire (SAQ). This study analyzes
      sexual attraction through the SAQ in 400 university students from a Peruvian
      catholic university. These participants -191 women and 209 men- show a very
      diverse curricular background. The following hypotheses were tested: a) the
      structure of the SAQ, pointing out two concepts: attraction to men and attraction
      to women; b) the high inverse correlation between these two concepts or factors;
      c) the specific impact of this context in sexual attraction: higher percentage of
      attracted by none of the sexes and lower percentage of attracted to the opposite
      sex, in comparison with other contexts; and d) the Lippa prediction (2006, 2007),
      regarding a higher polarization of sexual attraction for men than for women.
      Results support the first three hypotheses. Clarifications are laid down with
      regard to the fourth one. Discussion focuses on theoretical and applied
      advantages of using the SAQ as opposed to the frequent use of a single item of
      sexual attraction for each sex.

PMID- 22379723
TI  - Lesbian, Gay, and Bisexual Identity Scale (LGBIS): construct validation,
      sensitivity analyses and other psychometric properties.
AB  - According to Mohr and Fassinger (2006), identity is seen as both self
      identification and collective identification with values, beliefs, traits or
      behaviours and attachments. Their Lesbian, Gay, and Bisexual (LGB)
      multidimensional identity model accounts for important variables regarding the
      constitution of identities. This model not only accesses numerous dimensions of
      the lives of LGB individuals, but is also based on a body of research that
      recognizes how LGB difficulties are caused by societal intolerance and
      marginalization (Mohr & Fassinger, 2000). The Lesbian, Gay, and Bisexual Identity
      Scale (LGBIS; Kendra & Mohr, 2008) constitutes an operationalization of this
      multidimensional model, and the aim of this article is to present its construct
      validity by analysing its factor structure using a sample of Portuguese lesbian,
      gay and bisexual participants. Results from exploratory and confirmatory factor
      analyses, as well as from factor invariance analysis across sub-samples are
      presented. In a general way, the factor structure obtained in this study follows
      the original proposal of Kendra and Mohr's (2008) LGBIS. Moreover, scale
      sensitivity analyses are presented in order to check for eventual differences in
      the factor structure and/or factor intercorrelations regarding participant gender
      and sexual orientation. These results are then discussed in the light of LGB
      identity models.

PMID- 22379724
TI  - Anxiety, depression and coping: CDI, MASC and CRI-Y for screening purposes in
      schools.
AB  - This study used depression (CDI - Kovacs, 1981), anxiety (MASC - March, 1997) and
      coping strategy (CRI-Y - Moos, 1993) scales and studied the fitness and
      discriminant validity of reduced versions. The sample consisted of 916 Portuguese
      pupils, 54.3% feminine, aged 10 to 21 years old. The participants were selected
      from a set of public schools nation-wide. Two classes were chosen from the 5th to
      the 12th grades. A set of principal component analyses was carried out in a
      randomly chosen sample (n = 394) and all the three reduced measures were found to
      be strongly correlated with the previous. Confirmatory factor analyses (CFA)
      using the other part of the sample (n = 522) revealed adjustment indexes
      suggesting a good fit for both the whole model and gender and age groups
      separately. All scales revealed a good internal consistency. Globally, girls were
      more anxious and developed more coping strategies than boys. Older students
      tended to be less depressed, while younger adolescents present higher scores in
      depression and anxiety and less coping strategies. Reduced scales are sensitive
      to gender and age differences and can be used in school settings in order to
      establish a baseline and roadmaps for both universal and selective mental health
      school based programs.

PMID- 22379725
TI  - Health and safety at work in the transport industry (TRANS-18): factorial
      structure, reliability and validity.
AB  - In this article, we study the psychometric properties of a short scale (TRANS-18)
      which was designed to detect safe behaviors (personal and vehicle-related) and
      psychophysiological disorders. 244 drivers participated in the study, including
      drivers of freight transport vehicles (regular, dangerous and special), cranes,
      and passenger transport (regular transport and chartered coaches), ambulances and
      taxis. After carrying out an exploratory factor analysis of the scale, the
      findings show a structure comprised of three factors related to
      psychophysiological disorders, and to both personal and vehicle-related safety
      behaviors. Furthermore, these three factors had adequate reliability and all
      three also showed validity with regard to burnout, fatigue and job tension. In
      short, this scale may be ideally suited for adequately identifying the safety
      behaviors and safety problems of transport drivers. Future research could use the
      TRANS-18 as a screening tool in combination with other instruments.

PMID- 22379726
TI  - Psychometric properties of the Spanish Human System Audit Short-Scale of
      transformational leadership.
AB  - The aim of this research is to examine the psychometric properties of a Spanish
      version of the Human System Audit transformational leadership short-scale (HSA
      TFL-ES). It is based on the concept of Bass developed in 1985. The HSA-TFL is a
      part of the wider Human System Audit frame. We analyzed the HSA-TFL-ES in five
      different samples with a total number of 1,718 workers at five sectors.
      Exploratory Factor Analysis corroborated a single factor in all samples that
      accounted for 66% to 73% of variance. The internal consistency in all samples was
      good (alpha = .92 - .95). Evidence was found for the convergent validity of the
      HSA-TFL-ES and the Multifactor Leadership Questionnaire. These results suggested
      that the HSA-TFL short-scale is a psychometrically sound measure of this
      construct and can be used for a combined and first overall measurement.

PMID- 22379727
TI  - DSM-Oriented Scales of the Child Behavior Checklist and Youth Self-Report in
      clinically referred Spanish children.
AB  - The Achenbach System of Empirically Based Assessment (ASEBA) is an example of the
      efforts to integrate categorical and dimensional assessment methods. The latest
      editions of the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR)
      included the DSM-Oriented Scales, constructed in rational manner based on the
      items making up these inventories. OBJECTIVE: To analyze the psychometric
      properties of the DSM-Oriented Scales of the CBCL and YSR. METHOD: A clinical
      sample of 420 children and adolescents (aged 8-17 years) was assessed with the
      CBCL and YSR, with a structured diagnostic interview and with measures of
      functional impairment to study the reliability and validity of the DSM-Oriented
      Scales. RESULTS: Internal consistency ranged from moderate to good for all the
      scales except the DSM-Anxiety Problems Scale. Agreement between parents and
      children ranged between moderate and low values. Kappa coefficients showed
      moderate agreement in the different symptoms. The DSM-Oriented Scales presented
      acceptable diagnostic power for DSM-IV disorders and a significant relationship
      with measures of functional impairment. CONCLUSION: The DSM-Oriented Scales
      constitute a useful approach from the dimensional model to the DSM-IV disorders
      in Spanish clinical population.

PMID- 22379728
TI  - Validity evidence based on internal structure of scores on the Spanish version of
      the Self-Description Questionnaire-II.
AB  - The aim of this study was to analyze the reliability and validity evidence of
      scores on the Spanish version of Self-Description Questionnaire II (SDQ-II). The
      instrument was administered in a sample of 2022 Spanish students (51.1% boys)
      from grades 7 to 10. Confirmatory factor analysis (CFA) was used to examine
      validity evidence based on internal structure drawn from the scores on the SDQ
      II. CFA replicated the correlated II first-order factor structure. Furthermore,
      hierarchical confirmatory factor analysis (HCFA) was used to examine the
      hierarchical ordering of self-concept, as measured by scores on the Spanish
      version of the SDQ-II. Although a series of HCFA models were tested to assess
      academic and non-academic components organization, support for those hierarchical
      models was weaker than for the correlated 11 first-order factor structure.
      Results also indicated that scores on the Spanish version of the SDQ-II had
      internal consistency and test-retest reliability estimates within an acceptable
      range.

PMID- 22379729
TI  - Validation of the Basic Psychological Needs in Exercise Scale in a Portuguese
      sample.
AB  - In line with self-determination theory (SDT: Deci & Ryan, 1985, 2002) the
      satisfaction of the basic psychological needs for autonomy, competence, and
      relatedness has been identified as an important predictor of behavior and optimal
      functioning in various contexts including exercise. The lack of a valid and
      reliable instrument to assess the extent to which these needs are fulfilled among
      Portuguese exercise participants limits the evaluation of causal links proposed
      by SDT in the Portuguese exercise context. The aim of the present study was to
      translate into Portuguese and validate the Basic Psychological Needs in Exercise
      Scale (BPNES: Vlachopoulos & Michailidou, 2006). Using data from 522 exercise
      participants the findings provided evidence of strong internal consistency of the
      translated BPNES subscales while confirmatory factor analysis supported a good
      fit of the correlated 3-factor model to the data. The present findings support
      the use of the translated into Portuguese BPNES to assess the extent of basic
      psychological need fulfilment among Portuguese exercise participants.

PMID- 22379730
TI  - Psychometric properties of the Spanish version of the Thougth-Shape Fusion
      Questionnaire.
AB  - The objectives of the study were to analyze the psychometric properties, factor
      structure and internal consistency of the Spanish version of the Thought-Shape
      Fusion Questionnaire (TSF-Q), as well as to determine its validity by evaluating
      the relationship of the TSF-Q to different instruments. Two groups were studied:
      one comprising 146 patients with a diagnosis of anorexia (n = 82), bulimia (n =
      33) or unspecified eating disorder (n = 31), and another group of 115
      undergraduates with no history of psychological disorder. All participants
      completed the TSF-Q, TAF-Q, EDI-2, STAI, BDI and SCL-90-R. Differences in TSF-Q
      scores between the diagnostic subgroups were also analyzed. Two factors were
      obtained which coincided with the two sections indicated by the authors of the
      questionnaire: conceptual and interpretative. The internal consistency of the TSF
      Q and its subscales was determined by means of Cronbach's alpha, with values
      ranging between .93 and .96. The correlations with other instruments reflected
      adequate validity. There were no significant differences between the diagnostic
      subgroups. The Spanish version of the TSF-Q meets the psychometric requirements
      for measuring thought-shape fusion and shows adequate internal consistency and
      validity.

PMID- 22379731
TI  - Computerized adaptive testing: the capitalization on chance problem.
AB  - This paper describes several simulation studies that examine the effects of
      capitalization on chance in the selection of items and the ability estimation in
      CAT, employing the 3-parameter logistic model. In order to generate different
      estimation errors for the item parameters, the calibration sample size was
      manipulated (N = 500, 1000 and 2000 subjects) as was the ratio of item bank size
      to test length (banks of 197 and 788 items, test lengths of 20 and 40 items),
      both in a CAT and in a random test. Results show that capitalization on chance is
      particularly serious in CAT, as revealed by the large positive bias found in the
      small sample calibration conditions. For broad ranges of theta, the
      overestimation of the precision (asymptotic Se) reaches levels of 40%, something
      that does not occur with the RMSE (theta). The problem is greater as the item
      bank size to test length ratio increases. Potential solutions were tested in a
      second study, where two exposure control methods were incorporated into the item
      selection algorithm. Some alternative solutions are discussed.

PMID- 22379732
TI  - Effects of mercury chloride (HgCl2) on Betta splendens aggressive display.
AB  - Mercury chloride (HgCl2) is a toxic mercury salt and a major pollutant, that can
      be found in soil, water and air, with influences on behavior, physiology and
      adaptation to the environment. In this study two experiments were designed to
      examine interactions and effects of HgCl2 on some behavioral patterns of Siamese
      fighting fish (Betta splendens). In the first experiment we tested the effect of
      a progressive dose (five 0.04 mg) on aggressive display with exposure to a
      mirror, whereas in the second experiment we tested the effect of an acute dose
      (0.2 mg) on the aggressive display with exposure to a mirror. The experiments
      were performed on 5 consecutive sessions at intervals of 18 hours between
      sessions. Differences of performance were shown by subjects in the acute and
      progressive treatments when compared with a control treatment in the majority of
      behaviors evaluated, namely Floating, Slow Swimming, Wavy Swimming, Emerging,
      Bend, Square Move and Motor Display Components. Acute treatment was different
      from control only on Show Body, while the progressive group differed on Resting,
      Horizontal Display and Appropriate Display Components. Differences between
      Correlate Display Components and Total were also shown. Both the acute and
      progressive contamination with HgCl2 decrease the motor activity in the
      aggressive display, mirror-image test of Betta splendens, mainly on the
      progressive dose. This implies an impairment on feeding behavior, predator
      avoidance, reproductive behavior, mate choice and territoriality. These results
      suggest that in this fish species, the progressive dose has a greater effect on
      behavior in general and that both the acute and progressive contamination with
      mercury chloride affect many other aspects of behavior.

PMID- 22379733
TI  - Risk factors related to febrile morbidity after abdominal hysterectomy.
AB  - OBJECTIVE: To assess risk factors related to febrile morbidity (FM) after
      abdominal hysterectomy for non-malignant diseases. MATERIAL AND METHOD:
      Retrospective review and analysis of the data was carried out on the medical
      records of patients who had undergone total abdominal hysterectomy (TAH) with or
      without bilateral salpingo-oophorectomy (BSO) for non-malignant gynecological
      diseases during the period of January 1, 2006 to July 31, 2007. Patients who had
      had fever before surgery, had been treated with antibiotics within 1 week prior
      to surgery, had an emergency operation or incomplete data were excluded RESULTS:
      FM was found in 47 of the 450 patients (10.4%) and unexplained fever was the most
      common cause of febrile morbidity. Type of operation, operative time, estimated
      blood loss, indication for surgery, antibiotic therapy use, and surgeons' skill
      were all statistically significant risk factors when univariate analysis was
      used. After multiple logistic regressions were analyzed, however, only type of
      operation and skill of surgeons were still significant risk factors. CONCLUSION:
      The significant risk factors related to febrile morbidity were type of operation,
      and surgeons' skill.

PMID- 22379734
TI  - Semi-nested Taqman real-time quantitative PCR for noninvasive prenatal diagnosis
      of Bart's hydrops fetalis.
AB  - BACKGROUND: Non-invasive prenatal diagnosis based on detection of fetal cell-free
      DNA is limited when mother and father are both carriers for the same autosomal
      recessive mutation. OBJECTIVE: Develop the semi-nested Taqman real-time PCR for
      quantification of alpha-thalassemia-1 SEA type deletion allele in plasma of alpha
      thalassemia-1 SEA carriage pregnancies. MATERIAL AND METHOD: Plasma DNA was
      extracted from six women who carried fetuses with normal, 11 with heterozygote
      alpha-thalassemia-1 SEA type deletion and seven with Bart's hydrops fetalis. DNA
      was amplified using conventional PCR with the primary specific primer set for
      alpha-thalassemia-1 SEA type deletion. PCR product was then subjected to the semi
      nested real-time PCR using the secondary specific primer and Taqman probe set for
      alpha-thalassemia-1 SEA type deletion. The standard curve was constructed using
      ten-fold serial dilutions of conventional PCR product of the heterozygote alpha
      thalassemia-1 SEA type deletion. RESULTS: Women who carried fetuses with Bart's
      hydrops fetalis displayed a trend toward higher mean copy number of alpha
      thalassemia-1 SEA type deletion allele vs. women who carried fetuses with normal
      and heterozygote, albeit not reaching statistical significance. CONCLUSION: The
      maternally inheritedfetal allele present in maternal plasma is difficult to
      discern the fetal cell-free DNA from a higher background DNA of the mother Thus,
      further investigation is needed to improve the diagnosis ofBart's hydrops fetalis
      using this technique.

PMID- 22379735
TI  - The prevalence of hepatitis B in premarital counseling clinic at Siriraj
      Hospital.
AB  - OBJECTIVE: To study the prevalence and associating factors of hepatitis B
      infection in the Premarital Counseling Clinic at Siriraj Hospital. MATERIAL AND
      METHOD: The data (medical history, physical examination, and Hepatitis B profile)
      was collected from medical records of 740 couples who attended the Premarital
      Counseling Clinic in Siriraj Hospital between September 2005 and December 2009
      for this retrospective study. RESULTS: The prevalence of positive HBsAg in
      couples who attended the Premarital Counseling Clinic, Siriraj Hospital was 4.2%,
      which was 3.0% in male and 1.2% in female. The mean age of male was 32.9 +/- 5.1
      years old and 30.7 +/- 3.9 years old in female. History of hepatitis B
      vaccination was found less in male (male 6.1% vs. female 8.8%). Four point two
      percent of participants were positive HBsAg but negative of HBsAb. Twenty-four
      couples were at risk or 3.2%. Male gender and history of no hepatitis B
      vaccination was significantly associated with positive HBsAg. No significant
      difference was found between age and occupation. CONCLUSION: The prevalence of
      positive HBsAg in the Premarital Counseling Clinic, Siriraj Hospital was 4.2%.
      Male gender and history of no hepatitis B vaccination had significant association
      with positive HBsAg.

PMID- 22379736
TI  - Clinical indicators for pulmonary arterial hypertension in thalassemia.
AB  - OBJECTIVE: To explore clinical indicators for pulmonary arterial hypertension
      (PAH) in thalassemia (Thal). MATERIAL AND METHOD: A study was conducted in
      thalassemia patients at Chiang Rai Hospital, Chiang Rai, Thailand. Pulmonary
      artery systolic pressure (PASP) was determined by doppler echocardiography and
      PAH was defined as PASP > 35 mmHg. Patient characteristics were extracted from
      medical records. Characteristics of patients with and without PAH were compared.
      Risk indicators were explored with logistic regression analysis. RESULTS: Two
      hundred twenty four patients were included, 144 E/beta-Thal, 37 homozygous beta
      Thal and 43 Hb H disease. There were 65 patients (29.0%) with PAH, 53 (81.5%)
      with E/beta-Thal, 8 (12.3%) with homozygous beta-Thal and 4 (6.2%) with Hb H
      disease. In a multivariable analysis, features significantly associated with PAH
      were E/beta-Thal (OR = 1.98, 95% CI; 1.29-3.01) and post splenectomy status (OR =
      2.36, 95% CI; 1.17-4.73). CONCLUSION: Significant indicators for PAH in
      thalassemia were E/beta-Thal and post splenectomy status.

PMID- 22379737
TI  - Role of clinical parameters for predicting the cause of upper gastrointestinal
      bleeding.
AB  - BACKGROUND: Upper gastrointestinal bleeding (UGIB) has been classified into
      portal and non-portal hypertension (PHT) bleeding causes. Differentiating the two
      major categories of UGIB is therefore important for selection of the appropriate
      empirical treatment. OBJECTIVE: To evaluate the potential of certain clinical
      parameters for predicting the cause of UGIB. MATERIAL AND METHOD: The records of
      patients with UGIB who underwent endoscopy within 72 hours of diagnosis were
      retrospectively examined for the clinical parameters. Potential predictive
      factors for categorizing the cause of UGIB were identified by univariate and
      multivariate analysis. RESULTS: One hundred forty six UGIB patients were enrolled
      in the present study. One hundred nine patients had non-PHT bleeding and 37
      patients were PHT bleeding. Multivariate analysis identified three independent
      factors for predicting PHT bleeding, presence of signs of chronic liver disease
      or PHT (Odds ratio (OR) 51.1, p < 0.05), presence of underlying cirrhosis (OR
      28.4, p < 0.05) and an initial hematocrit < 30% (OR 12.7, p < 0.05). A
      presentation with coffee ground vomitus was the only factor that indicated a
      reduced possibility of PHT bleeding (OR 0.1, p < 0.05). CONCLUSION: The presence
      of underlying cirrhosis, signs of chronic liver disease or portal hypertension
      and an initial hematocrit < 30% were significantly correlated with PHT bleeding
      while the presentation of coffee ground vomitus indicated a less likely chance of
      PHT bleeding.

PMID- 22379738
TI  - Vitamin E supplement improves erythrocyte membrane fluidity of thalassemia: an
      ESR spin labeling study.
AB  - BACKGROUND: Beta-thalassemia/Hemoglobin E (beta-thal/Hb E) is prevalent in
      Thailand. The imbalance of globin chains in red blood cells is the primary cause
      of this anemic disease. The excess alpha-globin in beta-thal/Hb E causes typical
      damage(s) to membrane of erythroblasts and erythrocytes. By using three
      paramagnetic labeled compounds (5-, 12-, and 16-spin labeled stearic acids, SLS),
      the changes of the molecular motion in the lipid bilayer of thalassemic RBCs that
      have structural modification can be detected. OBJECTIVE: to investigate
      erythrocyte membrane fluidity and the effect of vitamin E treatment in beta
      thalassemia/Hemoglobin E patients by using spin labeling techniques. MATERIAL AND
      METHOD: The erythrocyte membrane fluidity was investigated in nine splenectomized
      and five non-splenectomized beta-thalassemia/hemoglobin E (beta-thal/Hb E)
      patients using EPR spin labeling techniques. To determine the effect of vitamin E
      on erythrocyte membrane fluidity, only the splenectomized patients were enrolled.
      Patients were divided into two groups. The first group received 350 mg vitamin E
      daily for a period of 1 month (n = 5) and the second group received placebo for
      an equal period (n = 4). Three paramagnetic fatty acid, 5-, 12-, and 16-doxyl
      stearic acids, (5-, 12- and 16-DS) were used to label phospholipids layer near
      both the surface (5-DS) and the deeper hydrophobic region of membrane (12-and 16
      DS). Lipid peroxidation (TBARs) was measured using a colorimetric method. Vitamin
      E was measured with high performance liquid chromatography (HPLC). RESULTS:
      Significantly higher values of erythrocyte membrane fluidity were revealed with
      12-, 16-DS in splenectomized patients, as compared with non-splenectomized
      patients and normal subjects. In 3-thal/Hb E patients, fluidity values, both
      outer hyperfine splitting (2T(//)) and order parameter (S) of 12-DS showed
      inverse correlation with serum TBARs. There was no significant difference between
      the fluidity values measured with 5-DS. After vitamin E supplementation, the
      erythrocyte membrane fluidity was decreased in almost all patients. In contrast
      to the vitamin E supplementation group, increased erythrocyte membrane fluidity
      was demonstrated in the placebo group. Vitamin E supplementation also had effect
      on other clinical parameters such as increased plasma vitamin E, decreased serum
      TBARs and no change in hemoglobin. CONCLUSION: The present results suggested the
      abnormal motion of lipid in the deeper phospholipids region of membrane. In
      addition, vitamin E supplementation may have a role in the prevention of
      erythrocyte membrane damage of these patients.

PMID- 22379739
TI  - Factors influencing loss to follow-up after elective inguinal herniorrhaphy.
AB  - OBJECTIVE: To identify risk factors associated with losses to follow-up after
      inguinal herniorrhaphy and to examine whether these factors are associated with
      higher risks for recurrence according to the literature. MATERIAL AND METHOD:
      Records of inguinal hernia patients who underwent elective inguinal herniorrhaphy
      between January 1998 and November 2006 were reviewed. Factors potentially
      associated with loss to follow-up included demographic variables, type of hernia,
      predisposing factors, type of anesthesia, surgeon experience, type of repair, and
      early operative complications. Loss to follow-up was defined as the absence of
      follow-up information three months after herniorrhaphy for at least two years.
      RESULTS: There were 1,451 patients with 1,727 hernia operations. Of these, 981
      operations (57%) were lost to follow-up. On multivariable analysis, factors
      associated with loss to follow-up included younger age, male gender secondary
      hernia, tissue-based repair, indirect inguinal hernia, and no postoperative
      complications. Many of these factors were not known to be associated with
      increased recurrence after hernia repair CONCLUSION: Hernia repairs lost to
      follow-up were systematically different from those not lost to follow-up, but
      factors related to these losses were not clearly or uniformly associated with
      higher risks for recurrence according to the literature.

PMID- 22379740
TI  - Incisional surgical site infection in colorectal surgery patients.
AB  - BACKGROUND: Knowledge of specific risk factors for incisional Surgical Site
      Infection (SSI) is essential to create a specific SSI risk stratification index
      for colorectal surgery patients. OBJECTIVE: Identify factors increasing the risk
      of incisional SSI that lead to the development of a more efficient tool for
      predicting and comparing surgical site infection rates among surgeons and
      institutions performing the same type of procedure for colorectal surgery
      patients. MATERIAL AND METHOD: The authors conducted a prospective incisional SSI
      surveillance in 229 consecutive patients who underwent open colon and rectal
      resections performed in Phramongkutklao Hospital between October 1, 2008 and
      September 30, 2010. Independent risk factors for SSIs were identified by
      multivariate analysis. RESULTS: The present study identified six independent risk
      factors significantly associated with a higher risk of incisional SSI that
      included Body mass index (BMI) > 30 (Odd ratio (OD) = 4.4; 95% confidence
      interval (CI) = 1.235-15.502; p = 0.022), hypoalbuminemia (< 3.5 g/dl) (Odd ratio
      (OR) = 2.8; 95% confidence interval (CI) = 1.003-7.587; p = 0.049), Hartmann's
      procedure (Odd ratio (OR) = 2.6; 95% confidence interval (CI) = 1.037-6.729; p =
      0.042), postoperative hypotension, (Odd ratio (OR) = 2.3; 95% confidence interval
      (CI) = 1.043-5.268; p = 0.039) and postoperative hypothermia (Odd ratio (OR) =
      5.6; 95% confidence interval (CI) = 1.112-28.482; p = 0.037). CONCLUSION: Risk
      factors identified in the present study can be considered for creating a specific
      incisional SSI risk stratification index for colorectal surgery patients. This
      specific risk stratification index will be a more efficient tool for predicting
      and comparing SSI rates among surgeons and institutions.

PMID- 22379741
TI  - Variation of prophylactic antibiotic in laparoscopic cholecystectomy:
      Songklanagarind Hospital perspective.
AB  - OBJECTIVE: Evaluate the effectiveness of variation of prophylactic antibiotic in
      laparoscopic cholecystectomy. MATERIAL AND METHOD: A retrospective data review
      was undertaken of patients who received a laparoscopic cholecystectomy between
      January 1, 2005 and December 31, 2008 in Songklanagarind Hospital. The prevalence
      of surgical site infection (SSI), the variation of antibiotic prescription, and
      associated factors with SSI were reviewed and analyzed. RESULTS: Four hundred
      thirty nine patients received a successful laparoscopic cholecystectomy. The
      prophylactic antibiotic was utilized in 328 patients (74.7%). Cefazolin was the
      most common antibiotic used. Only 3 patients (0.9%) received the antibiotic
      according to the recommendation of center for disease control and prevention
      (CDC). The SSI was accounted in 41 patients (9.3%); 29 had the prophylactic
      antibiotic, while 12 did not. There was no statistically significant difference
      in the prevalence of SSI between the two groups (p = 0.54). Factor significantly
      associated with SSI was the operative time more than three hours (p = 0.03).
      CONCLUSION: Various patterns of prophylactic antibiotic were encountered. The
      practice variation seemed to be ineffective in the prevention of SSI. The
      selectively risk factors should be considered in the antibiotic prophylaxis.

PMID- 22379742
TI  - Incidence and risk factors associated with hearing loss in high-risk neonates in
      Srinagarind Hospital.
AB  - OBJECTIVE: To determine incidence and risk factors associated with hearing loss
      in high-risk neonates in Srinagarind Hospital. STUDY DESIGN: Prospective cohort
      study. MATERIAL AND METHOD: High-risk neonates were screened with TEOAE/AABR. All
      infants were followed for hearing and developmental evaluation until one year of
      age. RESULTS: Four hundred twenty five neonates underwent hearing screening
      tests. Nine infants (2.1%) had abnormal TEOAE, AABR and ABR tests. During follow
      up, two of the nine infants that had abnormal initial hearing tests were found to
      have normal hearing at eight and nine months of age. Therefore, seven high-risk
      neonates (1.6%) had permanent hearing loss. Significant risk factors for
      permanent hearing loss were craniofacial anomalies, very low birth weight, low
      Apgar scores at 5 minute and mechanical ventilation usage for more than five
      days. CONCLUSION: Continuing evaluation of hearing and development during follow
      up is important in children with abnormal hearing tests. Invasive procedures as
      early intervention during the first six months of life should be considered with
      caution because some premature infants can have false positive tests or transient
      hearing loss and subsequently have normal hearing and development.

PMID- 22379743
TI  - A randomized, prospective, double-blind study of the efficacy of dexpanthenol
      nasal spray on the postoperative treatment of patients with chronic
      rhinosinusitis after endoscopic sinus surgery.
AB  - OBJECTIVE: To assess the efficacy of dexpanthenol nasal spray compared with
      normal saline spray in the postoperative treatment of patients with chronic
      rhinosinusitis (CRS) who underwent endoscopic sinus surgery (ESS). MATERIALS AND
      METHOD: A prospective, randomized controlled study was conducted in CRS patients
      who underwent ESS. The enrolled patients had never been operated intranasally.
      These patients received either dexpanthenol or normal saline nasal spray
      intranasally four times a day for six weeks post-operatively. RESULTS: Fifty CRS
      patients were recruited in the present study. Age ranged from 23 to 63 years
      (means 43.4 +/- 11.2 years). Forty-four percent of patients were diagnosed as CRS
      without nasal polyps (NP) (CRSs NP) and 56% were CRS with NP (CRSw NP). Twenty
      five cases were randomly assigned to use dexpanthenol nasal spray whereas the
      other 25 cases used normal saline nasal spray. The preoperative severity of CRS,
      determined by the computerized tomography (CT) scan scoring system of Lund-McKay
      was 13.9 +/- 6.2 in the dexpanthenol group and 13.6 +/- 6.9 in the normal saline
      group, which were not statistically different (p > 0.05). The endoscopic scoring
      was 10.2 +/- 2 in the dexpanthenol group and 10.7 +/- 3 in the normal saline
      group, which were not statistically different (p > 0.05). The mucociliary transit
      time improvement (time difference between pre- and post-treatment by nasal spray)
      was 8.4 +/- 3.3 minutes in the dexpanthenol group and 1.7 +/- 1.2 minutes in the
      normal saline group, which were statistically different (p < 0.05). CONCLUSION:
      The majority of the postoperative symptom scores and all of the endoscopic scores
      of the dexpanthenol group were not statistically different from those of the
      normal saline group. However, dexpanthenol nasal spray has superior efficacy
      compared with normal saline nasal spray on improvement of mucociliary clearance
      and nasal discharge in the postoperative care of CRS patients after ESS.

PMID- 22379744
TI  - Impact and appropriateness of the emergency ultrasonography in a tertiary care
      hospital.
AB  - OBJECTIVE: To quantify the notion of the impact of ultrasonography (US) on and
      the appropriateness of its use in, the diagnosis and treatment of emergency
      conditions. MATERIAL AND METHOD: A prospective study was conducted between
      September 2006 andApri 2007 at a tertiary care hospital. US was performed or
      supervised by experienced staff radiologists during the working hours and by
      final year radiology residents during the off-hours. Data collection forms were
      filled by radiology residents. The final discharge diagnoses were obtained from
      medical charts and computerized records. Data collected included age, gender
      provisional diagnosis, ultrasound findings, the discharge diagnosis, time of
      ultrasound examination, other radiologic investigations and therapeutic
      interventions. Outcomes included the impact, appropriateness, and diagnostic
      accuracy of US. RESULTS: Six hundred eighteen patients underwent 702 emergency
      ultrasound examinations. The median age was 51 years. Approximately 50% were
      male. The anatomical region most commonly examined was the abdomen (80%). US had
      an impact on clinical management in 85% of all examinations. Appropriate use of
      US was seen in 64% of all examinations. The overall accuracy of US was 90%.
      Factors associated with higher impact included suspected urological, vascular and
      musculoskeletal conditions, while vague abdominal conditions were associated with
      less impact. CONCLUSION: The impact of US on the management of emergency
      conditions was high and most requests for US were appropriate. However a more
      efficient use of emergency US is still possible, especially for abdominal
      conditions.

PMID- 22379745
TI  - Treatment of laryngopharyngeal reflux: a comparison between domperidone plus
      omeprazole and omeprazole alone.
AB  - OBJECTIVE: To evaluate the efficacy of domperidone in combination with omeprazole
      in the treatment of laryngopharyngeal reflux (LPR) compare to omeprazole alone.
      MATERIAL AND METHOD: A prospective and randomized study included seventy patients
      with a reflux symptom index (RSI) 13 or more. They received either domperidone 10
      mg thrice daily plus omeprazole 20 mg twice daily or omeprazole alone for three
      months. RSI was assessed at baseline and after three months of treatment.
      RESULTS: Total RSI as well as several subscores were comparable between groups
      before the treatment. After three months of the treatment, moderate improvement
      of total RSI was shown in both groups (72.7%, 67.5%). The reduction of total RSI
      and individual subscores were statistically significant within each group (p <
      0.001 each). Comparing between each treatment group, the mean difference of total
      RSI and individual subscores did not shown any statistically differences (p >
      0.05 each) at the end of the study period. CONCLUSION: Domperidone in combination
      with omeprazole is not superior to omeprazole alone in the treatment of LPR.

PMID- 22379746
TI  - Vertebral body compression fracture: discriminating benign from malignant causes
      by diffusion-weighted MR imaging and apparent diffusion coefficient value.
AB  - OBJECTIVE: To evaluate the diagnostic performance of apparent diffusion
      coefficient (ADC) value in discriminating benign from malignant vertebral
      compression fracture. MATERIAL AND METHOD: 22 symptomatic patients with
      compression fracture of vertebra referred for conventional MRI spines during
      January 2009-March 2010 underwent additional diffusion weighted MR techniques.
      Evaluation of diffusion weighted MR imaging and quantified ADC value from
      reconstructed ADC map were performed. The accuracy, sensitivity, specificity,
      positive predictive value and negative predictive value of apparent diffusion
      coefficient (ADC) value were calculated. RESULTS: A total of 39 vertebral
      fractures; 7 malignant compression fractures and 32 benign compression fractures
      were evaluated. The difference between ADC values of malignant, benign
      compression fracture and normal vertebrae were statistically significant (p <
      0.0001). The accuracy, sensitivity and specificity were 89.7%, 85.7% and 90.6%
      respectively with the ADC threshold of 0.89 to discriminate malignancy.
      CONCLUSION: The ADC promises to be an effective implement for characterization of
      vertebral body compression fracture in differentiating benign and malignant
      compression fractures.

PMID- 22379747
TI  - Human epidermal growth-factor receptor 2 overexpression in gastric carcinoma in
      Thai patients.
AB  - OBJECTIVE: To determine human epidermal growth-factor receptor 2 (HER2) protein
      overexpression frequency and the concordance rate between immunohistochemistry
      and fluorescence in situ hybridization techniques in gastric carcinoma. MATERIAL
      AND METHOD: A retrospective analysis of gastric adenocarcinomas obtained from 224
      adult patients between January 2000 and December 2008 were performed. The
      paraffin-embedded tissues were sliced into 4-microm-thick sections and analyzed
      for HER2 protein expression levels by immunohistochemistry (IHC) using an
      automated slide-staining IHC system. Breast carcinoma tissues were included in
      every staining batch as positive control. In order to detect and quantify
      amplification of the HER2, the authors performed fluorescence in situ
      hybridization (FISH) using PathVysion HER2 DNA Probe Kit. The IHC results were
      independently recorded by two pathologists using the standard HER2 scoring system
      for gastric carcinoma. FISH results were interpreted using standard guideline as
      employed in breast carcinoma. The two-tailed-Fisher's exact test was used to
      assess the concordance between IHC and FISH results. RESULTS: HER2 protein
      overexpression level was identified in 9% (20 in 224 cases) of the gastric
      tumors; 80% of which were well or moderately differentiated and of the intestinal
      or mixed type. However HER2-overexpressing tumors comprised only 16% of the
      intestinal/mixed-type or well/moderately differentiated tumors. There was no
      signal obtained from 29 specimens from FISH studies. Thus, the overall results of
      IHC and FISH methods were concordant in 88% (171 out of 195, p < 0.001).
      CONCLUSION: There is a significant concordance rate between IHC and FISH in
      gastric carcinoma. The present study is the first HER2 study of such carcinoma in
      Thai patients.

PMID- 22379748
TI  - Xerostomia, hyposalivation and oral microbiota in patients using antihypertensive
      medications.
AB  - OBJECTIVE: Oral dryness can contribute to several diseases in the oral cavity.
      The objective of the present study was to compare the subjective oral dryness,
      salivary flow rates, the number of oral microbiota, and the dental status between
      medicated hypertensive patients and control subjects. MATERIAL AND METHOD: Four
      hundred subjects including 200 ambulatory hypertensive patients who were taking
      antihypertensive medications and 200 control subjects were included. Each
      subject's medical history was reviewed. The subject's oral health status,
      salivary flow rate, and the number of oral microbiota were also evaluated.
      RESULTS: The prevalence rate of xerostomia in the medicated hypertensive group
      was 50% whereas only 25.5% of the control group had xerostomia (p < 0.05). Using
      modified Schirmer test (MST), the mean unstimulated salivary flow rate of the
      medicated hypertensive group (23.11 +/- 6.08 mm/3 min) was significantly lower
      than that of the control group (31.30 +/- 3.36 mm/3 min) (p < 0.05). In addition,
      the mean stimulated salivary flow rate of the medicated hypertensive group (0.73
      +/- 0.30 ml/min) was also significantly lower than that of the control group
      (1.31 +/- 0.34 mi/min) (p < 0.05). The strongest associated factor for dry mouth
      was the use of antihypertensive medications (OR = 6.28). The mean levels of
      mutans streptococci, Lactobacilli spp. and Candida spp. in the medicated
      hypertensive group were significantly higher than in the control group (p <
      0.05). Furthermore, medicated hypertensive patients were more likely to have
      missing teeth compared to control subjects. CONCLUSION: Xerostomia,
      hyposalivation, and increasing number of oral microbiota were more prevalent in
      hypertensive patients taking antihypertensive medications.

PMID- 22379749
TI  - Remission rate of atypical antipsychotic treatment of bipolar depression:
      experience at Srinagarind Hospital, northeast Thailand.
AB  - OBJECTIVE: To determine the remission rate when using atypical antipsychotic
      treatment for bipolar depression at Srinagarind Hospital, Khon Kaen, Thailand.
      MATERIAL AND METHOD: The authors reviewed the patient records for 18 persons,
      both in- and out-patients, with DSM-IV-TR bipolar depression, treated with
      atypical antipsychotic(s), at the Department of Psychiatry, Srinagarind Hospital,
      between May 2005 and April 2008. The remission rate using atypical antipsychotic
      treatment was assessed using survival analysis while the patterns of prescribing
      atypical antipsychotics were delineated using percentages. RESULTS: Of the 18
      patients, 15 fulfilled the remission criteria. The mean time to remission was
      10.3 weeks (SD 8.4). The incidence-density of the remission rate for bipolar
      depression treated with atypical antipsychotics was 8.1 per 100 person-weeks (SD
      2.4, 95% CI 4.5-13.4). One patient achieved remission using only atypical
      antipsychotic monotherapy while 17 received a combination of atypical
      antipsychotics plus one or more of the following: antidepressants,
      anticonvulsants, anxiolytics and/or lithium. The present study revealed that
      remission was 1.4 times higher among females than males and 13 times higher among
      married than singles. CONCLUSION: The incidence-density of the remission rate
      using atypical antipsychotics for treatment of bipolar depression was 8.1 per 100
      person-weeks. Almost all of the patients were treated with a combination of
      atypical antipsychotics plus other groups of medications. Higher remission was
      associated with females and married persons.

PMID- 22379750
TI  - An assessment on Thai emergency medical services performance: the patient
      perspective.
AB  - BACKGROUND: Emergency medical services (EMS) have been steadily developed in
      Thailand. However the patient perspective has not been explicitly considered in
      performance assessment thus far although it is a key consideration for quality
      improvement in public organizations. OBJECTIVE: To investigate the Thai patient
      experience in EMS and emergency departments (ED) and help Thai leaders guide
      future improvements. MATERIAL AND METHOD: The present study was a survey of
      selected ED of 14 public hospitals in four geographical regions. Five hundred
      fifty patients from each hospital were interviewed between June and July 2009.
      The data were collected by medical records review and face-to-face interview.
      RESULTS: Six thousand four hundred forty four patients [average age of 36.01
      years (range: 0-98), almost 50% female, 95% local residents] participated in the
      survey. Ambulances staffed with paramedics or trained volunteers transported
      7.28% of the patients. Of those, 80% to 95% were satisfied, rating the service as
      'safe'. Volunteer transfers had lower satisfaction scores. Patients spent an
      average of 63.8 minutes in the ED. Almost all patients were satisfied and would
      recommend the services to their friends or relatives. The most common factors
      contributing to dissatisfaction were with waiting time for consultation and pain
      management. CONCLUSION: There is high patient satisfaction with emergency
      services in public hospitals. Nonetheless, the lower satisfaction for volunteer
      ambulance service, the concern about waiting time, and pain management highlights
      opportunity for improvement. The rapid, low-cost patient surveys combined with
      paper-based medical record review can yield useful information for quality
      improvements

PMID- 22379751
TI  - Painless thyroiditis complicating with hypercalcemic encephalopathy.
AB  - BACKGROUND: Severe hypercalcemia has rarely been reported in patients with
      hyperthyroidism. Although the pathogenesis is not clear; it is believed to be due
      to activation of osteoclasts resulting in excessive bone resorption. OBJECTIVE:
      To recognize the unusual cause of hypercalcemia from painless thyroiditis, which
      could manifest with transient hyperthyroidism in the early stage. CASE REPORT: A
      70-year-old woman presented with watery diarrhea, nausea and vomiting and
      significant weight loss for two months. Initially, she was misdiagnosed as having
      Graves'disease from her clinical presentation and thyroid function tests. Oral
      propylthiouracil was given to treat hyperthyroidism. However two weeks after
      discharge, she developed altered consciousness due to severe hypercalcemia. After
      combined treatment of hypercalcemia and severe hyperthyroidism, her symptoms
      resolved quickly. Later on, her thyroid function tests switched to subclinical
      hypothyroid at two months after initial presentation. No concurrent pathological
      conditions could be found to explain the other causes of hypercalcemia.
      Therefore, painless thyroiditis complicated with severe hypercalcemia was
      subsequently diagnosed based on her clinical course. CONCLUSION: Hypercalcemic
      encephalopathy is an uncommon manifestation of hyperthyroidism that should be
      kept in mind in patients who demonstrated clinical pictures of hyperthyroidism
      and alteration of consciousness. Moreover the present case emphasizes the
      consideration of painless thyroiditis as a differential diagnosis of
      hyperthyroidism because anti-thyroid medications were not indicated in this
      condition.

PMID- 22379752
TI  - Transcatheter aortic valve implantation (TAVI): first case in Thailand.
AB  - Aortic valve replacement (AVR) is the standard treatment for patients with
      symptomatic severe aortic stenosis (AS). However many patients are not offered
      surgery due to high surgical risk for open AVR. Transcatheter aortic valve
      implantation has been an alternative to open heart surgery in patients with
      symptomatic severe aortic stenosis (AS) who are not suitable for open surgery.
      The first transcatheter aortic valve implantation in Thailand via the transapical
      route is described. An 87-year-old woman with symptomatic severe AS, calcified
      aorta and peripheral arterial disease, who was at high surgical risk, was
      successfully treated, and had good functional and haemodynamic results at six
      months follow-up.

PMID- 22379753
TI  - Postsurgical high flow priapism treated by transarterial embolizaton: a case
      report.
AB  - The authors report a case of painful priapism, caused by iatrogenic arterial
      injury from endoscopic internal urethrotomy procedure for stricture urethra,
      which increased blood circulation in the penis. On physical examination, there
      was sustained erection, turgid corpora, swelling of penis and prepuce and
      tenderness at the perineal area. Bilateral selective internal iliac angiograms
      showed a prominent right internal pudendal artery and deep penile artery
      terminating in an arterio-sinusoidal fistula. This case was treated by
      superselective arterial embolization with Gelfoam pledgets and the treatment was
      successfully carried out in one session. However the patient sill had erectile
      dysfunction for six months. After that, the erectile dysfunction gradually
      improved. Finally, the patient had normal erectile function one year after
      embolization.

PMID- 22379754
TI  - Situs inversus totalis and ultrastructure of respiratory cilia: report of a
      cadaveric case.
AB  - Situs inversus totalis is the complete reversal of positions of major thoracic
      and abdominal organs. The present study reports the reversed structures and
      histology of the epithelium of bronchus of a female cadaver 87 years of age,
      which was found during the dissection in a medical course of gross anatomy.
      Opening the thoracic cage, the apex of heart was projected to the right side
      (dextrocardia) while the right and left lungs were alternated. Intra-abdominal
      organs were also completely alternated, as the liver situated on the left while
      spleen on the right and the same as the abdominal intestinal tract. The superior
      and inferior vena cavae located on the left side and drained blood into the left
      atrium. The azygos vein was on the right. The histology of the epithelium of
      bronchus and the transmission electron microscopy of the cilium ultrastructure
      were normal. Cardiac displacement seems to be associated with malrotation of the
      heart tube leads to dextrocardia and causes the inversion of positions of the
      thoracic and abdominal organs. The incidence of situs inversus totalis is
      approximately 1:10,000 and may be associated with primary ciliary dyskinesia
      (PCD) which refers to the dysfunction of cilia. PCD is also known as Kartagener
      syndrome (KS) which is characterized by situs inversus, bronchiectasis, chronic
      sinusitis and infertility, KS represents 20-25% of situs inversus totalis.
      However in the present study, the histology and ultrastructure of cilia appear
      normal.

PMID- 22379755
TI  - [Hearing loss of aging].
AB  - The gradual hearing loss is seen in every people as they get older. In this
      symposium, anatomy and physiology of the ear were talked at first. Next, diseases
      which cause hearing disturbance were explained. Especially, we focused on the age
      related hearing loss. It was emphasized that we should speak to elderly people
      very slowly and clearly so that they could understand us well. At last, the
      usefulness and progress of hearing aids were introduced. It is very important to
      tune their hearing aids to the individual. We hope that this symposium would help
      the attendance to enjoy every day of their lives.

PMID- 22379756
TI  - Maintaining the communication and information tool of the Belgian anesthesiology
      community.

PMID- 22379757
TI  - Central neural blockade in patients with a drug-induced alteration of
      coagulation. Third edition of the belgian Association for Regional Anaesthesia
      (BARA) Guidelines.

PMID- 22379758
TI  - Medication in the perioperative period: stop or continue? A review.
AB  - Preoperative evaluation of medication is important as part of the anesthetic
      plan. The aim of this manuscript is to evaluate and compare through literature
      review the existing evidence to support optimal perioperative medication
      management.

PMID- 22379759
TI  - Gross tracheal deviation: airway challenges and concerns--two case reports.
AB  - Practical guidelines and algorithms may not always help in difficult airway
      management. Large thyroid swellings may be responsible for several difficulties
      during the perioperative period, such as distortion of the airway, endocrine
      disturbances and metabolic effects. We here discuss the airway management of two
      patients with huge thyroid enlargement and gross tracheal deviation. One of those
      patients had also retrosternal extension of goiter. Both patients were scheduled
      for an excision of their colloid goiter.

PMID- 22379760
TI  - Anaphylactic shock and hyperfibrinolysis measured with thromboelastography.
AB  - This case report presents anaphylactic shock in which hyperfibrinolysis was
      diagnosed with Thromboelastography (TEG). A 45 year old female patient was
      scheduled for vacuum-assisted wound closure. At induction, she developed an
      anaphylactic shock that stabilized after standard treatment. TEG analysis
      revealed hyperfibrinolysis. Surgery was delayed and there were no signs of
      spontaneous bleeding. A repeat TEG analysis performed 30 minutes later showed a
      completely normalized coagulation pattern. Few reports have documented the
      association between anaphylactic shock and hyperfibrinolysis. This case
      illustrates the transient and short-lived nature of the phenomenon. The
      mechanisms and potential consequences are discussed.

PMID- 22379761
TI  - Unintentional side error for continuous sciatic nerve block at the popliteal
      fossa.
AB  - Among all fields of healthcare about 45% of medical errors occur in the operating
      theatre. Wrong site procedures remain one of the most preventable medical errors.
      Unintentional wrong-sided peripheral nerve block is relatively a rare event in
      anesthesia care. However, the incidence is unknown but each time wrong-sided
      block occurs it represents a mistake and a potential for harm. The surgical
      safety checklist was established in 2008 by the world Health organization (WHO)
      as a part of the "Safe surgery save Lives" initiative. We report in this article
      a case of wrong sided continuous popliteal sciatic nerve block and discuss the
      role of the WHO's checklist in preventing wrong side peripheral nerve block and
      surgery.

PMID- 22379762
TI  - [The development for real-time sampling and display in epicardial mapping
      system].
AB  - In order to realize real-time sampling and display in 128-channeled Epicardial
      Mapping System whose sampling frequency is 2 kHz per channel, the article
      introduces a mapping software and preliminarily validates its practicability. The
      software is designed in MFC, using multiple-thread technology and buffering and
      pumping values method.

PMID- 22379763
TI  - [Design and test of non-blood contacting pneumatic ventricle assistance device].
AB  - This paper presents a design of non-blood contacting pneumatic ventricle
      assistance device, which consisted of several parts, such as dual-cavity cardiac
      assistance cup, ventricle assistance controller, computer, vacuum pump, and air
      compressor. And the performance of the non-blood contacting pneumatic ventricle
      assistance device on mock circulation loop is introduced, which is very close to
      the normal cardiac output.

PMID- 22379764
TI  - [Realization of mobile phone based wireless blood pressure monitoring system and
      its preliminary implementation].
AB  - A novel system which could measure blood pressure wirelessly through mobile phone
      has been proposed and developed. It consisted of a blood pressure signal recorder
      based on MCU (Micro Control Unit), which could transmit measured data via
      Bluetooth, and a software embedded on mobile phone, which could calculate the
      value of blood pressure and the rate of heart beat. The measurement results could
      easily be stored in text documents or in picture format. Detailed scheme and
      design of each module in the system was illustrated and experiments were
      conducted to demonstrate the reliability and stability of the device. A series of
      new conceptual explorations into blood pressure related issues were conducted
      with this system, including the variational blood pressure at different time
      periods in a day, the effect of posture on the measurement results and the impact
      of movements on blood pressure.

PMID- 22379765
TI  - [The research of decoded compression arithmetic for medical high-frequency
      ultrasound coded excitation imaging].
AB  - This paper combined the coded excitation with the technique of ophthalmic high
      frequency ultrasonic imaging, and raised a new high-velocity data detection and
      signal processing method. 16 bit Golay complementarity sequences were produced by
      FPGA, which excited the probe to produce ultrasonic waves. Data detection circuit
      achieved the digitalized of the 15 MHz high-frequency ultrasonic echo signals in
      real time. Sampling rate was 120MHz, and sampling bit was 14 bit. Decoded
      compression arithmetic was realized by FPGA in real time, in which A code
      compression was alternated with B code compression. The return echo was
      correlated with the corresponding decode filter A and filter B respectively, and
      then the echo was delayed and summed to complete the decoding process. The
      experiment indicated that coded excitation can effectively increase the range of
      mainlobe and decrease the range of sidelobe. This technique can effectively raise
      the signal-to-noise ratio, and has significant research value in advancing the
      ophthalmic ultrasonic image quality and raising the safety of the equipment.

PMID- 22379766
TI  - [Teeth segmentation from CBCT images using deformable triangle mesh model].
AB  - Considering the dental CBCT images' characteristics, the method of deformable
      surface of 3D triangle mesh model is proposed. The method uses a deformable model
      which is initialized from an icosahedron and evolves to fit the teeth's surface
      by the application of the locally adaptive external forces computed from the
      image data and internal forces coming from the model itself. The experimental
      results indicate that the proposed method is robust and accurate.

PMID- 22379768
TI  - [A result analysis of gamma pass rates for IMRT verification for pinnacle
      planning system].
AB  - OBJECTIVE: The study was to explore effort of planning parameters by analyzing
      the result of Gamma pass rates for IMRT verification for Pinnacle planning
      system. METHODS: 5 Head Neck IMRT plans finished by Xio planning system were
      imported into Pinnacle planning system. Different algorithms and calculation
      grids were used to calculate the dose distributions for 3 orthogonal planes at
      isocenter which were exported in 3 kind grids. Mapcheck software was used to
      calculate the Gamma pass rate using the plane dose distributions from Xio system
      as the reference ones simulating the measurements. RESULT: The difference of
      Gamma pass rates for 3 kinds of algorithm and calculation grids were of
      statistical significance. CONCLUSION: The parameters in Pinnacle planning system
      may have influence on Gamma pass rates. It needs further discussion to directly
      use the Gamma pass rates in documents during the establishing of IMRT QA
      protocol.

PMID- 22379767
TI  - [Experimental study on the stimulating effect and the tissue compatibility of a
      new type of implanted gastric electrical stimulator].
AB  - A new type of gastric electrical stimulator (GES) was introduced. After the
      stimulator was implanted in beagle dogs, its stimulating effects and the
      pathological changes at the implant site were observed to study the safety and
      efficacy of stimulator as well as the tissue compatibility of the materials used.
      The results showed that, this type of stimulator was safe and capable of
      inhibiting food intake of the dogs, and that the materials used had good tissue
      compatibility.

PMID- 22379769
TI  - [Genotoxicity study of bone cement].
AB  - OBJECTIVE: To investigate the genotoxicity of bone cement. MATERIAL AND METHODS:
      Test article was mixed of liquid and the powder extract of bone cement. Using
      bacterial reverse mutation test (Ames test) and mouse lymphoma Assay (MLA) with
      and without metabolic activation S9. Ames test was performed by the plate
      incorporation method for its ability to induce reverse mutations in three
      treatment dosage groups: 25 microl/plate, 50 microl/plate, 100 microl/plate using
      S. typhimurium TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA; In MLA, the
      mutation frequency (MF) and the percentage of small colony mutants (SC%) of L5178
      tk(+/-) cells induced by bone cement at final concentration of 0.125%, 0.25% and
      0.5% (V/V) were calculated and assayed with +S9/3 h, - S9/3 h, -S9/24 h. RESULTS:
      Slight precipitations of two dosage group 50 microl/plate and 100 microl/plate
      were observed after phosphoric acid buffer solution or S9mix added. Growth
      inhibition effect exists in TA100, TA1535 and WP2 uvrA to varying degrees. Other
      groups did not cause obvious increases in the mean number of revertant per plate
      compared with negative control (DMSO). The result of MLA indicated no significant
      MF or SC% increases (P>0.05) observed comparing with negative control under all
      test conditions. CONCLUSIONS: The bone cement did not induce reverse mutation at
      his(-)/trp(-) and there was no obvious damage effect to gene tk(+/-) or
      chromosome under this study condition.

PMID- 22379770
TI  - [Application of vacuum-assisted venous drainage technology in minimally invasive
      cardiac surgery].
AB  - OBJECTIVE: To summarize the method and experience of cardiopulmonary bypass (CPB)
      with vacuum-assisted venous drainage technology (VAVD) in the minimally invasive
      cardiac surgery (MICS). METHODS: 35 cases of patients undergoing MICS were
      achieved femoral arterial cannula and femoral venous cannula. During the course
      of the CPB, we used the VAVD technology. At the same time, we selected 35 cases
      as control group.The time of the CPB, mechanical ventilation and ICU, and the
      amount of the urine, blood products, and chest drainage were recorded. RESULTS:
      The time of mechanical ventilation and ICU staying, the volume of the blood
      products and the volume drainage within 48 h postoperatively in the MICS group
      were significantly shorter and less than that in control group (P < 0.05).
      CONCLUSION: The use of VAVD in the MICS can increase the vena cava drainage
      effectively, and ensure the surgery safe and successful.

PMID- 22379771
TI  - [The application and development of computer vision technology in radiotherapy].
AB  - In this paper, the principle of computer vision was introduced and several
      typical radiotherapy devices based on computer vision were described, including
      their principle and applications.

PMID- 22379772
TI  - [The management of implantable medical device and the application of the internet
      of things in hospitals].
AB  - Implantable medical device is a special product which belongs to medical devices.
      It not only possesses product characteristics in common, but also has specificity
      for safety and effectiveness. Implantable medical device must be managed by the
      relevant laws and regulations of the State Food and Drug Administration. In this
      paper, we have used cardiac pacemakers as an example to describe the significance
      of the management of implantable medical device products and the application of
      the internet of things in hospitals.

PMID- 22379773
TI  - [Design and implementation of EMR information system in hospitals].
AB  - With the electronic medical records information system as the core of hospital
      information platform design, this paper introduces the design of the system which
      is structured for electronic medical records, and the advantage and effectiveness
      is also introduced. From the aspects of the concept, system framework, data
      integration, right frame and safety control, identity index and a clinical
      pathway, etc, the paper introduces the basic idea and process of the hospital
      information platform design, with the hospital recording electronic medical
      records as the core.

PMID- 22379774
TI  - [The design and realized of medical MR uniform field assistant software based on
      COM communication].
AB  - Traditional manual shimming measures and records data by highly accurate Tesla
      meters, then analyzes the data and puts small shimming magnet pieces to those are
      needed, and finally completes the shimming by repeating the above mentioned
      process. Because using Tesla meter to measure and record data takes much time,
      the efficiency of manual shimming is quite low. This article puts up an assisting
      way to shimming by using medical MRI shimming software designed and realized
      based on COM communications, thus enhances shimming efficiency greatly.

PMID- 22379775
TI  - [Research for the test method of polypropylene fiber liquid filtration membrane
      particles shedding].
AB  - Through five experiments, such as "Circle", "square", "side that does not shake",
      "burning edge", "filter", this paper discussed the effect of different
      experimental methods of polypropylene fiber liquid filtration membrane particles
      shedding. The results show that: the particles falling off the edge of the
      polypropylene fiber Double-sided liquid filtration membrane are very important
      and must be considered off the evaluation of particle pollution.

PMID- 22379776
TI  - [Study on selection of the EMC test system of medical electrical equipment].
AB  - The article introduces the EMC tests involved in YY0505-2005 (standard of Medical
      electrical equipment about EMC), and the requirements of test equipment meet the
      standard and practical tests. I hope it can be useful for select the EMC test
      system of Medical electrical equipment.

PMID- 22379777
TI  - [Discussion of leakage current measurement earthing].
AB  - According to the measurement requirements of leakage current from the national
      standards such as Standard GB9706.1-2007, this article describes the existing
      problems of isolated power earthing during leakage current measurement. Aiming at
      improving the measurement accuracy and protecting the security of testing
      engineers, we analyses several methods for isolated power earthing during the
      leakage current measurement, and various reasons of possible differences among
      test values of leakage current. Based on the existing national standards, this
      article proposes alternative testing methods for discussion.

PMID- 22379778
TI  - [Research on the issues in the process of post-market surveillance for medical
      devices based on the typical case analysis].
AB  - Regarding the information collected, analysis and actions that have been taken,
      the issues in the process of the Post-market Surveillance for Medical Device were
      analyzed, and some suggestions were given at the same time.

PMID- 22379779
TI  - [A perspective of the development of medical metrology].
AB  - This paper summarized the internal and external development of medical metrology,
      posed its main problem and studied its development trend.

PMID- 22379780
TI  - [The effect of transferrin detecting in digestive tract hemorrhage detection
      rate].
AB  - OBJECTIVE: To compare the sensitivity, the specificity and the anti-jamming of
      several excrement occult blood experimental techniques. To evaluate the effect of
      transferrin (Tf) in the excrement in the digestive tract hemorrhage detection
      rate. METHODS: For 600 patients of clinical suspicious digestive tract
      hemorrhage, take their excrement specimen, using the chemical process (pyramidon
      semi-quantitative examination law) to detect hemoglobin (Hb), and using
      monoclonal antibody colloidal gold method to detect Hb and Tf. RESULTS: Finally
      the hemoglobin chemical process (hereafter refers to as chemical process) to
      detect upper gastrointestinal hemorrhage with the positive rate 57.3%, and the
      detection of hemorrhage of lower digestive tract's positive rate is 44.8%;
      Hemoglobin monoclonal antibody colloidal gold method (hereafter refers to as
      colloid gold law) to examine upper gastrointestinal hemorrhage with a positive
      rate 60.4%, under examination hemorrhage with positive rate 77.6%; transferrin
      monoclonal antibody colloidal gold method (hereafter refer to as transferrin law)
      to examine upper gastrointestinal hemorrhage with a positive rate 82.3%,
      examination hemorrhage of lower digestive tract with a positive rate 66.4%; The
      union examination law (hemoglobin and transferrin to be detected twice, once
      positive that is positive) examines upper gastrointestinal hemorrhage the
      positive rate is 90.8%, hemorrhage of lower digestive tract's positive rate is
      97.6%. CONCLUSION: Excrement transferrin has the high detection rate in the upper
      gastrointestinal hemorrhage; Hb and the Tf combined examination may obviously
      raise the digestive tract hemorrhagic disease's positive detection rate.

PMID- 22379781
TI  - [Analysis of the design and renovation of mid-sized hospital's local area
      network].
AB  - To address several hospital network issues, this paper discusses the overall
      plan, design and renovation of hospital's Local Area Network, making full use of
      existing network facilities. The techniques, such as Physical Separation of
      Internal and External Network, HSRP, OSPF, All-Routers Networking Model, etc.,
      create features of extensibility, manageability, high safety, stability and so on
      to the overall network, and provide a reliable network platform to the function
      of the information systems.

PMID- 22379782
TI  - [Effects of electroacupuncture at "Futu" (LI 18), etc. on expression of spinal 5
      HT 1 AR mRNA, 5-HT 2 AR mRNA and protein in rats with neck incision pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at bilateral "Futu"
      (LI 18), etc. on the expression of 5-HT 1 A receptor (R) mRNA, 5-HT2 AR mRNA and
      protein in the spinal cord of rats with neck incision pain, so as to explore its
      underlying mechanism in relieving incision pain. METHODS: A total of 48 Wistar
      rats were randomly divided into control, model (incision pain), Futu (LI 18),
      Hegu (LI 4)-Neiguan (PC 6, LI 4-PC 6), Zusanli (ST 36)-Yanglingquan (GB 34)
      cervical cord (ST 36-GB 34 C) and lumbar cord (ST 36-GB 34 L) groups. A 1.5 cm
      longitudinal incision was made in the middle of the neck under Isoflurane
      inhalation anesthesia. Pain threshold (PT) was measured using radiant heat. EA (1
      2 mA, 2 Hz/15 Hz) was applied to bilateral LI 18, LI 4-PC 6, ST 36-GB 34 for 30
      min. The expression of 5-HT 1 AR mRNA, 5-HT 2 AR mRNA and protein in the cervical
      spinal cord (C1-C4) tissue, and 5-HT 1 AR mRNA and 5-HT 2 AR mRNA in the lumbar
      cord (L1- L3) were detected with Real-time PCR and Western blot analysis,
      respectively. RESULTS: After the operation, the thermal PT was shortened
      obviously In comparison with pre-operation (P < 0.05). Compared with post
      operation, the PT values were increased markedly in the LI 18 group and LI 4-PC 6
      group (P < 0.05), rather than in the ST 36-GB 34 group (P > 0.05). The expression
      levels of 5-HT 1 AR mRNA, 5-HT 2 AR mRNA and 5-HT 2 AR protein in the cervical
      cord of the model group were increased significantly compared with those of the
      control group (P < 0.05). In comparison with the model group, the expression
      level of 5-HT 1 AR mRNA was down-regulated considerably in the LI 18 and LI 4-PC
      6 groups (P < 0.05), and those of spinal 5-HT 2 AR mRNA and protein were up
      regulated significantly in the LI 18 and LI 4-PC 6 groups (P < 0.05). No
      significant changes were found in the expression of 5-HT 1 AR mRNA and 5-HT 2 AR
      mRNA in the ST 36-GB 34 C group in comparison with the model group (P > 0.05).
      The expression levels of 5-HT 1 AR mRNA and 5-HT 2 AR mRNA in the ST 36-GB 34 L
      group were significantly lower than those of the ST 36-GB 34 C group (P < 0.05).
      CONCLUSION: EA of LI 18 and LI 4-PC 6 can significantly suppress pain reaction of
      neck incision in the rat, which is closely associated with its effects in down
      regulating the expression of 5-HT 1 AR mRNA and in up-regulating 5-HT 2 AR mRNA
      and 5-HT 2 AR protein in the cervical spinal cord.

PMID- 22379783
TI  - [Effects of transcutaneous electrical acupoint stimulation combined with general
      anesthesia on changes of gastric dynamics in controlled hypotension dogs].
AB  - OBJECTIVE: To observe the effect of transcutaneous electrical acupoint
      stimulation (TEAS) combined with general anesthesia on gastric dynamics in
      controlled hypotension dogs, so as to provide experimental evidence for compound
      acupuncture anesthesia. METHODS: Eighteen male beagle dogs were randomly divided
      into general anesthesia group (GA group, n = 6), general anesthesia + controlled
      hypotension group (GA + OHT group, n = 6) and general anesthesia combined with
      TEAS + controlled hypotension group (TEAS group, n = 6). The latter two groups
      were administered with the same anesthetics [isofluane inhalation and intravenous
      sodium nitroprusside (SNP)] for inducing controlled hypotension (being the 40% of
      the baseline level). Beagles of the GA group were not treated with controlled
      hypotension (the initial concentration of SNP = 1 microg/kg x min(-1), and with
      an increase rate of 1 microg/kg x min(-1) until the controlled hypotension
      phase). In the TEAS group, TEAS [2 Hz/100 Hz, (4 +/- 1) mA]was applied to "Quchi"
      (LI 11) , "Zusanli" (ST 36), "Hegu" (LI 4), and "Sanyinjiao" (SP 6) from the
      beginning of the stable physiological condition phase to the end of the
      controlled-low mean arterial pressure (MAP) phase. Electrogastrogram (EGG) was
      recorded, and serum gastrin (GAS) and motilin (MTL) contents were detected by
      enzyme-linked immunosorbent assay. RESULTS: Compared with the basic level, the
      amplitude value of EGG at 60 mm after controlled hypotension in the GA + CHT
      group was significantly lower (P < 0.05), while the amplitude level of EGG of the
      TEAS group at the time-point of MAP recovery was significantly higher than those
      of the GA and GA + CHT groups (P < 0.05). No significant changes were found among
      the 3 groups in the frequency levels of EGG. At the time-points of MAP recovery
      and 2 h after MAP recovery, serum MTL and GAS levels in the TEAS group were close
      to their basic level (P > 0.05), and serum GAS level at the time-point of 2 h
      after MAP recovery in the TEAS group was considerably higher than those in the GA
      and GA + CHT groups (P < 0.05). Twenty-four, 48 and 72 h after MAP recovery,
      serum GAS levels in the TEAS group were moderately (24 h and 48 h ) and
      significantly (72 h) higher than that of the basic level. No significant
      differences were found between the GA and GA + CHT groups in serum MTL and GAS
      levels at the time-points of 2, 24, 48 and 72 h after MAP recovery (P > 0.05).
      CONCLUSION: TEAS combining with general anesthesia for controlled hypotension can
      improve the amplitude of EGG, and serum MTL and GAS contents, favoring the
      recovery of gastric dynamics and the functional protection of stomach.

PMID- 22379784
TI  - [Effects of moxibustion on gastric mucosal EGF and TGF-alpha contents and
      epidermal growth factor receptor expression in rats with gastric mucosal lesion].
AB  - OBJECTIVE: To observe the effects of moxibustion on contents of epidermal growth
      factor (EGF) and transforming growth factor-alpha (TGF-alpha) and epidermal
      growth factor receptor (EGFR) expression in the gastric mucosa tissue in rats
      with gastric mucosal lesion. METHODS: Thirty-six SD rats were randomly and
      equally divided into control, model and moxibustion groups. Gastric mucosal
      lesion model was duplicated by restraint and cool water immersion stress. Pre
      moxibustion was applied to "Zusanli" (ST 36) and "Zhongwan" (CV 12), "Pishu" (BL
      20) and "Weishu" (BL 21) alternately, once everyday for 8 days before modeling.
      The contents of EGF and TGF-alpha in gastric mucosa were detected by enzyme
      linked immunosorbent assay (ELISA) and the expression of EGFR determined by
      immunohistochemistry. RESULTS: Compared with the control group, only TGF-alpha
      content in the gastric mucosa in the model group was increased significantly (P <
      0.05). Compared with the model group, the EGF and TGF-alpha contents and EGFR
      immunoactivity in the gastric mucosa were increased significantly in the
      moxibustion group (P < 0.05, P < 0.01). CONCLUSION: Pre-moxibustion at ST 36, CV
      12, BL 20 and BL 21 can up-regulate gastric mucosal EGF and TGF-alpha contents
      and EGFR protein expression in gastric mucosa lesion rats, which may contribute
      to its effect in relieving stress-induced gastric mucosal injury.

PMID- 22379785
TI  - [Effect of eye-acupuncture on cerebral intracellular adhesion molecule-1
      expression in rats with acute cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of the eye-acupuncture therapy on cerebral
      intercellular adhesion molecule-1 (ICAM-1) expression in rats with acute cerebral
      ischemia-reperfusion injury (CI/RI) so as to reveal its underlying mechanism.
      METHODS: Forty male SD rats were randomly and equally divided into normal, sham
      operation (sham), model and eye-acupuncture groups. Acute CI/RI model was
      established by occlusion of the middle cerebral artery with a modified suture
      blocking method. Filiform needles were inserted into the "Qan" (Liver Area),
      "Shangjiao" (Upper Energizer Area), "Xiajiao" (Lower Energizer Area), etc. of the
      eye-acupuncture acupoints, and retained for 20 min. The treatment was conducted
      twice daily, 7 times altogether. Seventy-two hours after Acute CI/RI, the
      neurological behavior was assessed by ZeaLonga neurophysical impairment scale.
      Cerebral ICAM-1 protein and ICAM-1 mRNA expression levels were detected by
      Western blot (Penumbra area of the right cerebral infarction region) and real
      time-polymerase chain reaction (PCR) methods, respectively. RESULTS: After
      modeling, the neurophysical impairment score of the model group was increased
      from 0 to (2.63 +/- 0.92) points on the first day and (2.63 +/- 0.74) points 72 h
      following Acute CI/RI. Correspondingly, cerebral ICAM-1 protein and mRNA
      expression was up-regulated considerably in the model group than in the normal
      control group (P < 0. 01). In comparison with the model group, the neurologic
      impairment score, and cerebral ICAM-1 protein and mRNA expression levels of the
      eye-acupuncture group were down-regulated obviously (P < 0.01, P < 0.05). No
      significant differences were found between the normal control and sham groups in
      neurologic impairment score and the expression levels of the ICAM-1 protein and
      ICAM-1 mRNA(P > 0.05). CONCLUSION: Eye-acupuncture therapy can improve the
      cerebral ischemia-reperfusion injury induced behavior changes, which may be
      related to its effects in down-regulating the expression of cerebral ICAM-1
      protein and gene.

PMID- 22379786
TI  - [Effect of electroacupuncture of different regions of the auricle on epileptic
      seizures in epilepsy rats].
AB  - OBJECTIVE: To observe the anti-seizure effect of electroacupuncture (EA) at
      different sites regions of the auricle in awake rats. METHODS: Sixty male SD rats
      were randomly divided into model, ear-apex, ear-outer-margin, earlobe, cymba
      concha, cavitas-conchae groups (n = 10 in each group). A metal microelectrode
      (diameter: 50 microm) was implanted into the somatosensary cortex for recording
      the field potentials (FPs). Epileptic seizure model was established by
      intraperitoneal injection of pentylenetetrazol (PTZ, 60 mg/kg). EA (20 Hz, 1 mA)
      was applied to ear-apex, ear-outer-margin, earlobe, cymaba-concha and cavitas
      conchae for 30 min, respectively. The epileptic behavior changes (scores) were
      determined in the light of Racine's method, and the epileptic seizure was
      assessed according to the epileptic FPs (5-folds above the basic amplitude) of
      the cerebral cortex. RESULTS: In comparison with the model group, the latency of
      the first seizure of epilepsy in the ear-outer-margin, earlobe, cymba-concha,
      cavitas-conchae groups were increased significantly (P < 0.01), while the scores
      of epileptic behavior and the duration of seizure shown by FPs decreased
      considerably in the ear-apex, ear-outer-margin, earlobe, cymba-concha, cavitas
      conchae groups (P < 0.01). Comparison among the five EA treatment groups showed
      that the effects of both cymba-concha and cavitas-conchae groups were
      significantly superior to those of ear-apex, earlobe and ear-outer-margin groups
      in increasing the latency of the first seizure of epilepsy, and reducing the
      scores of the epileptic behavior and seizure duration (P < 0.01). No significant
      differences were found between the cymba-concha and cavitas-conchae groups in the
      above-mentioned 3 indexes (P > 0.05). CONCLUSION: EA of cymba-concha and cavitas
      conchae has a good effect in suppressing epileptic seizures, which may be
      mediated via the auricular branch of the vagus nerve.

PMID- 22379787
TI  - [Effect of electroacupuncture of "Taichong" (LR 3) on liver function in mild
      alcoholic liver injury rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Taichong" (LR 3)
      on liver function in rats with mild alcoholic liver injury (MALI) so as to
      explore the feasibility of acupuncture in improving mild alcoholic liver injury.
      METHODS: Forty SD rats were randomly divided into control, model, EA-LR 3 and EA
      non-acupoint groups (10 rats/group). MALI model was duplicated by intragastric
      administration of distillate spirit (14 mL/kg) for 12 hours. Rats of the control
      group were fed with the same volume of normal saline. EA (2 Hz, 6 V) was applied
      to bilateral "Taichong" (LR 3) and non-acupoint (the interspace between the 4th
      and 5th bones of toes in parallel with LR 3) for 30 min, respectively. At the end
      of experiments, rats were sacrificed for collecting liver tissues. The activities
      of alanine aminotransferase (ALT), aspartate aminotransferase (AST) of the liver
      supernatant were detected by using Lai's method. RESULTS: IIn comparison with the
      control group, liver ALT and AST activities in the model group were increased
      significantly (P < 0.05), while in comparison with the model group, liver ALT and
      AST levels in the EA-LR 3 group were down-regulated remarkably (P < 0.05). No
      significant changes were found in liver ALT and AST level in the EA-non-acupoint
      group (P > 0.05). There was no significant improvement in the pathological
      changes of liver in the EA-LR 3 and EA-non-acupoint groups. CONCLUSION: EA of
      "Taichong"(LR 3) may reduce distillate-spirit induced mild alcoholic liver injury
      in rats.

PMID- 22379788
TI  - [Electroacupuncture at "Zusanli"(ST 36) can inhibit frequencies of transient
      lower esophageal sphincter relaxation induced by gastric distention in cats].
AB  - OBJECTIVE: To observe the influence of electroacupuncture (EA) of "Zusanli" (ST
      36) and ST 36 + "Neiguan" (PC 6) on gastric distention induced transient lower
      esophageal sphincter relaxation (TLESR) in cats. METHODS: Forty cats were
      randomly divided into model (gastric distension) group, EA-ST 36 group, EA-PC 6
      group, EA-ST 36 + PC 6 group, EA-non-acupoint group, EA-ST 36 + saline (2 mL
      i.v.) group, EA-ST 36 + L-arginine (precusor of nitric oxide, 200 mg/kg i.v.)
      group, and EA-ST 36+Tacrine (cholinesterase inhibitor, 5.6 mg/kg i. p.) group,
      with 5 cats being in each group. TLESR model was established by extending the
      stomach with an air balloon. EA (2 Hz/100 Hz, 3-4 mA) was applied to bilateral ST
      36, PC 6 and ST 36 + PC 6 and non-acupoint (exterior-superior site of the hip)
      while gastric distension. L-Arginine was given 10 min before EA, and Tacrine was
      given 30 min before EA. The frequency of TLESR and lower esophageal sphincter
      pressure (LESP) were recorded by using a perfused sleeve assembly. RESULTS:
      Compared with the model group, the frequency of TLESR in 60 min as well as the
      percentage of common cavity during TLESR were significantly decreased in the EA
      ST 36, EA-PC 6, EA-ST 36 + PC 6, EA-ST 36 + saline groups (P < 0.05). Compared
      with the EA-ST 36 + saline group, the frequency of TLESR in 60 min was up
      regulated significantly in the EA-ST 36 + Tacrine group (P < 0.01) rather than in
      the EA-ST 36 + L-Arginine group, suggesting a reduction of the efficacy of EA-ST
      36 by cholinergic suppression (not by nitric oxide). No significant differences
      were found among the EA-ST 36, EA-PC 6 and EA-ST 36 + PC 6 groups in the
      frequency of TLESR and the percentage of common cavity (P > 0.05). In comparison
      with the baseline level, LESP was increased significantly only in the EA-ST 36
      group (P < 0.05). CONCLUSION: EA at ST 36 can reduce both the frequency of TLESR
      and the percentage of common cavity during TLESR in gastric distension cats,
      which may be mediated by cholinergic pathway.

PMID- 22379789
TI  - [Randomized controlled clinical trials for electroacupuncture treatment of
      urinary incontinence in stroke patients].
AB  - OBJECTIVE: To observe clinical efficacy of electroacupuncture (EA) for post
      stroke urinary incontinence in patients. METHODS: A total of 111 stroke
      inpatients with urinary incontinence were randomly divided into EA group (n = 56)
      and control group (n = 55). Patients of the control group were treated by
      administration of calcium ion antagon, angiotensin-converting enzyme inhibitor,
      angiotensin II receptor antagonist, compound thromb-clearing agent (i.v.),
      etc.,and acupuncture of Jianyu (LI 15), Xuehai (SP 10), etc. Patients of the EA
      group were treated by EA of bilateral Shenshu (BL 23), Huiyang (BL 35), etc.,
      combined with the treatment as the control group. The treatment was conducted
      once daily for 4 weeks. Crooks (1995) Scores of the clinical symptoms and
      clinical efficacy assessment were given before and after the treatment. RESULTS:
      After the treatment, the severity of urinary incontinence and symptom scores in
      both control and EA groups were decreased significantly in comparison with pre
      treatment (P < 0.01). Following the treatment, of the 55 and 56 stroke patients
      in the control and EA groups, 0 and 4 (7.1%) were cured in the symptoms of
      frequent micturition, urgency of micturition and incontinence of urine, 20
      (36.4%) and 35 (62.5%) were effective, 35 (63.6%) and 17 (30.4%) were invalid,
      with the effective rates being 36.4% and 69.6%, respectively. The therapeutic
      effect of EA group was apparently superior to that of the control group (P <
      0.01). In addition, the infection rate of the EA group was strikingly lower than
      that of the control group (P < 0.05). CONCLUSION: EA can lower the severity of
      urinary incontinence and improve clinical symptoms of micturition in stroke
      patients.

PMID- 22379790
TI  - [Comparison of therapeutic effects between plum-blossom needle tapping plus
      cupping and laser irradiation in the treatment of acute facial palsy patients
      with concomitant peri-auricular pain].
AB  - OBJECTIVE: To compare the therapeutic effects of plum-blossom needle therapy with
      cupping and laser irradiation in the treatment of acute facial paralysis with
      ipsilateral peri-auricular pain. METHODS: Sixty outpatients with acute facial
      paralysis and ipsilateral peri-auricular pain were divided into plum-blossom
      needle (treatment) group (n = 28) and laser-irradiation (control) group (n = 32).
      In the acute stage, patients of the treatment group were treated with plum
      blossom needle tapping in combination with cupping at Yifeng (TE 17) and Wangu
      (GB 12), while those of the control group treated with He-Ne laser irradiation
      over the same two acupoints until the peri-auricular pain disappeared. The
      treatment was given once daily. Following disappearance of the pain, routine
      acupuncture treatment of Yifeng (TE 17), Wangu (GB 12), Dicang (ST 4), etc. was
      given continuously to patients of the two groups, once daily for 20 times. The
      treatment times for healing ipsilateral peri-auricular pain, and the
      electromyogram (EMG, compound muscle action potential) of the ipsilateral
      musculus orbicularis oris were recorded. Scores of the facial nerve function were
      given to House-Brackmann Facial Nerve Grading System. RESULTS: The treatment
      times for healing peri-auricular pain in the treatment group and laser
      irradiation group were 2.9 +/- 1. 0 and 6.0 +/- 2.2 respectively (t = 6.816, P =
      0.000). The scores of House-Brackmann scale of the paralyzed side in the
      treatment group and control group were (3.3 +/- 1.5) points and (3.3 +/- 1.4)
      points (P > 0.05) before the treatment; (1.8 +/- 1.1) points and (2.5 +/- 1.2)
      points (P < 0.05) one month after the treatment, and (1.5 +/- 0.9) points and
      (2.2 +/- 1.5) points (P < 0.05) three months after the treatment, respectively.
      The amplitude ratios of compound muscle action potential between the affected
      side and the healthy side in the treatment group and control group were (52.1 +/-
      20.5)% and (51.2 +/- 22.6)% (P > 0.05) during the first two weeks after onset,
      and (79.2 +/- 11.3)% and (69.8 +/- 17.9)% (P < 0.05) three months after the
      treatment, respectively. CONCLUSION: Plum-blossom needle tapping plus cupping is
      significantly superior to that of He-Ne laser irradiation in reducing the
      treatment sessions for relieving peri-auricular pain during acute stage, and
      improving facial and muscular functions in the treatment of acute facial
      paralysis patients.

PMID- 22379791
TI  - [Observation on therapeutic effect of acupuncture of Back-shu acupoints for
      chronic fatigue syndrome patients].
AB  - OBJECTIVE: To observe the therapeutic effect and safety of acupuncture of Back
      shu points [Xinshu (BL 15), Pishu (BL 20), etc.] in the treatment of chronic
      fatigue syndrome (CFS). METHODS: A total of 120 CFS patients were equally
      randomized Into acupuncture and control groups. Acupuncture needles were inserted
      into bilateral Xinshu (BL 15), Pishu (BL 20), and Gaohuang (BL 43) points, once
      daily for 4 weeks except weekends. For patients of the control group, acupuncture
      needles were inserted into the shallow layer of the non-acupoints (two mid-points
      of the horizon lines passing through the crossing-points of the 1st and 2nd
      branches of the Gallbladder Meridian and the crests of 4th, 5th and 11th thoracic
      vertebrae). General health scale (SF-20) and Chalder fatigue scale were used to
      measure the CFS patients' degree of general health. A follow-up survey was
      carried out 3 months after the last treatment. RESULTS: In comparison with pre
      treatment, the scores of Chalder fatigue scale were decreased significantly in
      both treatment and control groups (P < 0.01), while the scores of physiological
      function (PF) and general health (GH) of SF-20 in both acupuncture groups and
      those of the role function (RF), social function (SF), mental health (MH) and
      pain sensation (PS) in the treatment group were increased apparently after the
      treatment (P < 0.05, P < 0.01). The scores of Chalder Scale and PF, RF, SF, GH,
      MH, PS and the CFS patients' satisfication degrees 4 weeks (64.4% and 36.7%) and
      3 months (62.3% and 32%) after the treatment in the treatment group were
      significantly superior to those of the control group (P < 0.05). CONCLUSION:
      Acupuncture at Back-shu point has a good therapeutic effect (including immediate
      and midterm effect) in the treatment of chronic fatigue syndrome patients.

PMID- 22379792
TI  - [Research on characteristics of different clinical conditions treated by red-hot
      acupuncture needle based on data mining needle].
AB  - OBJECTIVE: To analyze the regularities and characters of clinical application of
      red-hot needle therapy in ancient and modern literature of Chinese medicine by
      using data mining techniques, so as to provide a reference for study on the
      specificity of efficacy of red-hot needle therapy. METHODS: Sample data was
      collected from some medical books, medical cases, reports of modern journals for
      calculating frequent item sets by using methods of association rules of data
      mining. Then, the collected data was extracted, sorted out, and summed up by
      using our newly developed literature database platform of red-hot needle therapy
      in order to find out the most suitable indications of this therapy in clinical
      practice. RESULTS: A total of 6 categories of clinical conditions treated by red
      hot needle therapy were found. Among them, the frequency times (percentages) of
      red-hot needle application for surgical problems appeared in journals, medical
      cases and medical books are 287 times (49.83%), 235 times (48.96%), 154 times
      (41.73%), respectively. The frequency times of red-hot needle application for
      disorders of internal medicine and dermatology are 276 times and 360 times. Among
      the 115 categories of clinical conditions or diseases treated by red-hot needle
      appeared in journals, arthromyodynia and struma are frequently found, with the
      frequency being 115 and 46 times, separately. The total effective rates of the
      present therapy from higher to lower are 99.46% for pediatric problems, 98.65%
      five sensory organs department, 97.32% surgery, 96.66% dermatology, 96.34%
      gynecology, and 93.95% internal medicine, respectively. Among the 97 types of
      clinical conditions recorded in the literature on medical cases, aural verruca is
      more frequently seen apart from arthromyodynia and struma. In medical books, 94
      types of clinical conditions treated by red-hot needle therapy are found,
      including 32 types of problems of internal medicine. CONCLUSION: Data mining
      results show that red-hot needle therapy has been widely used in different
      clinical departments, and more frequently used in surgery (mainly orthopedic and
      general surgery), internal medicine (mainly neurology and gastroenterology),
      dermatology.

PMID- 22379793
TI  - [Ideas of standardization evaluation on acupuncture skills: enlightened by
      quantitative appraisal of surgical skills in Europe and North America].
AB  - Acupuncture manipulation skills are the core of acupuncture therapy. Traditional
      acupuncture skills evaluation is based on experts' subjective assessment which is
      deficient in reliability and validity. Certain progresses on the quantitative
      research on acupuncture skills have been made in China, while there is still a
      long way to go before the formation of the consummate standardization evaluation
      system on acupuncture skills. Actually, quantitative appraisal on surgical skills
      has been developed for a long time in Europe and North America. Since acupuncture
      could be considered as a kind of skills of minimally invasive surgery because
      small wounds would be generated by needles, the theories and methods in surgical
      quantitative appraisal could be utilized. For instance, scales could be designed
      to evaluate the operation modes in acupuncture skills and precise instruments
      could be used in the measurement of acupuncture skills. Then standard databases
      on common acupuncture manipulations would be built. Moreover, in terms of the
      characteristics of acupuncture skills, high-fidelity simulators should be
      designed or standardized patients should be trained for the assessment of "Deqi"
      (arrival of qi)feelings. Thereby, an appropriate standardization evaluation
      system for acupuncture skills would be created gradually.

PMID- 22379794
TI  - [Progress of studies on regulative effect of acupuncture on activities of
      vasoactive intestinal peptide].
AB  - Vasoactive intestinal peptide (VIP) is a widely studied peptide hormone,
      distributes in multiple systems of the human body and plays a variety of
      biological effects in many diseases. In recent years, there have been abundant
      researches about the regulative effect of acupuncture on changes of VIP
      activities. The authors of the present paper make a review about its research
      progress in recent ten years from (1) effect of acupuncture on VIP functional
      activities of the gastrointestinal tract; (2) involvement of VIP in
      electroacupuncture (EA) induced improvement of gastric mucosal and cerebral blood
      flow (3) effect of EA on functions of VIP being as a neurotransmitter; (4) effect
      of EA on VIP-involved immune regulation function. Moreover, the authors also make
      a prospect on the correlation between the effect of acupuncture and VIP.
      Currently, the mechanism of VIP underlying the efficacy of acupuncture still
      remains unknown, and needs further investigation.

PMID- 22379795
TI  - [Research on basic questions of intellectual property rights of acupuncture and
      moxibustion].
AB  - Along with the modernization and internationalization of acupuncture-moxibustion
      (acu-moxibustion), the issue of intellectual property rights has been becoming
      prominent and remarkable increasingly. In the present paper, the authors explain
      the basic issues of acu-moxibustion learning from the concept, scope, subject,
      object, contents and acquisition way of intellectual property rights. To make
      clear these questions will help us inherit and carry forward the existing
      civilization achievements of acu-moxibustion, and unceasingly bring forth new
      ideas and further improvement in clinical application, so as to serve the
      people's health in a better way.

PMID- 22379796
TI  - [Clinical application of otopoint-pellet pressure combined with patient
      controlled intravenous analgesia to lower limb orthopedic operation].
AB  - OBJECTIVE: To observe the therapeutic effect of otopoint-pellet pressure (OPP)
      combined with patient controlled intravenous analgesia (PCIA) for lower-limb
      surgery of orthopedics. METHODS: A total of 120 lower-limb orthopedic operation
      patients were randomized into OPP + PCIA group (n = 60) and PCIA group (n = 60).
      The patient's pain degree was evaluated by visual analogue score (VAS). RESULTS:
      In comparison with the simple PCIA group, VAS levels were significantly lower in
      the OPP + PCIA group than in the PCIA group 2, 6, 24 and 48 h after operation.
      The number of patients with post-operative reactions of nausea, vomiting and
      urinary retention in the OPP+ PCIA group was remarkably lower than that of OPP
      group (P < 0.05). CONCLUSION: OPP + PCIA is superior to simple PCIA in post
      operative analgesia and reducing post-operative adverse reactions in lower-limb
      orthopedic operation patients.

PMID- 22379797
TI  - [Metabolic engineering strategies for carboxylic acids production by
      Saccharomyces cerevisiae---a review].
AB  - Carboxylatic acids have been widely used in food, pharmaceutical and chemical
      industries. As a eukaryotic model organism, Saccharomyces cerevisiae is thought
      as cell factory to produce organic acids through manipulating metabolic pathway.
      In this review, we addressed the metabolic engineering strategies to construct a
      high titer route converting pyruvate to target carboxylate, and to explore how to
      divert the carbon flux to desired product from ethanol. Furthermore, we also
      discussed the mechanisms for carboxylate transport and energy involved in.
      Finally, the relevant strategies for development in future are proposed.

PMID- 22379798
TI  - [Bacterial capsular polysaccharide--a review].
AB  - The study on bacterial capsular polysaccharide is deeper with the development of
      the molecular biology, saccharide chemistry and immunology. Not only the
      character and structure of bacterial capsular polysaccharide was researched, but
      also the genes related to the synthesis, regulation and pathogenicity. This
      review focuses on the chemical structure, synthesis genes, mechanisms of the
      diversity, synthesis regulation, function, pathogenicity and application of the
      bacterial capsular polysaccharide. The research hot spots are also summarized to
      supply the basic theory and threads to study and apply bacterial capsular
      polysaccharide.

PMID- 22379799
TI  - [Principle and application of DNA-based stable isotope probing---a review].
AB  - Microbial communities are the engines that drive the global biogeochemical cycle
      of carbon and nitrogen essential for life on Earth. However, microorganisms have
      evolved as a result of complex interactions with other organisms and
      environments. Deciphering the metabolism of microorganisms at the community level
      in nature will be crucial for a better understanding of the mechanisms that lead
      to the enormous divergence of microbial ecophysiology. Due to the immense number
      of uncultivated microbial species and the complexity of microbial communities,
      delineating community metabolism proves a virtually insurmountable hurdle. By
      tracing the heavy isotope flow of key elements such as carbon and nitrogen, DNA
      based stable isotope probing (DNA-SIP) can provide unequivocal evidence for
      substrate assimilation by microorganisms in complex environments. The essential
      prerequisite for a successful DNA-SIP is the identification, with confidence, of
      isotopically enriched 13C-DNA, of which the amount is generally too low to allow
      the direct measurement of 13C atom percent of nucleic acid. The methodological
      considerations for obtaining unambiguous DNA highly enriched in heavy isotope are
      presented with emphasis on next-generation sequencing technology and
      metagenomics.

PMID- 22379800
TI  - [Diversity of culturable bacteria in the typical frozen soil areas in China].
AB  - OBJECTIVE: The diversity of culturable bacteria in the six frozen soils from High
      latitude area and High-altitude area were analyzed by using culture-dependent
      approaches. METHODS: Three solidified media were used to isolate culturable
      bacteria. Bacterial 16S rRNA genes of the isolates were PCR amplified using
      bacteria-universal primers, and then were sequenced. The resulting bacterial 16S
      rRNA gene sequences were subjected to phylogenetic analysis. RESULTS: The
      abundance of culturable bacteria ranged from 4.70 x 10(3) to 2.57 x 10(5) colony
      forming units (CFU) per gram of soils (dry weight). A total of 144 bacterial
      strains were obtained. The bacterial isolates from the High-latitude area were
      affiliated with three phyla (Firmicutes, Gammaproteobacteria, and
      Betaproteobacteria) with Pseudomonas, Bacillus, and Paenibacillus strains being
      dominant. The bacterial isolates from High-altitude area could be grouped into
      three different phyla (Gammaproteobacteria, Firmicutes, and Bacteroidetes) with
      Pseudomonas strains be dominant. CONCLUSION: The culturable bacteria are abundant
      and diverse in the frozen soils of High-latitude and High-altitude areas. The
      results also showed that the culturable bacterial community structure varied
      among different research areas. Our data have implications for a better
      understanding of culturable bacterial community in the frozen soils in China.

PMID- 22379801
TI  - [Phylogenetic and physiological diversity of cold-adapted bacteria producing beta
      galactosidase from permafrost sediments of the bottom layer of the Glacier No. 1
      in the Tianshan Mountains].
AB  - OBJECTIVE: The purpose of this research is to isolate cold-adapted bacteria
      producing beta-galactosidase from permafrost sediments of the bottom layer of the
      Glacier No. 1 in the Tianshan Mountains, China. Physiological test and
      phylogenetic analysis were undertaken to expand our knowledge on diversity of
      psycrotrophic and psycrophlic bacteria. METHODS: By using lactose as the main
      carbon source and X-Gal as chromogenic agent in the medium, cold-adapted strains
      producing beta-galactosidase were detected. Taxonomic identity and genetic
      diversity of strains isolated were determined by spatial 16S rRNA gene sequences
      and rep-PCR fingerprint. In addition, we analyzed the phonotypic differences
      between strains showing high similarity of 16S rRNA gene sequences, including the
      optimum growth temperature, salt tolerance, ability to use carbon source and
      antibiotic resistance spectra. RESULTS: Of the total 90 cold-adapted bacterial
      strains isolated, we found 25 stains with beta-galactosidase activity, 76% of
      which were Gram-positive bacteria. According to growth temperature range, 80% of
      strains producing beta-galactosidase were identified as psychrophilic bacteria,
      20% as psychrotrophs. Phylogeneticlly, the beta-galactosidase-producing bacterial
      isolates fell in four groups: subclasses alpha, beta and gamma of Proteobacteria,
      and Firmicutes phylum. CONCLUSION: The results enrich our knowledge on the
      phylogenetic and physiological diversity of cold-adapted strains producing beta
      galactosidase in cold environments.

PMID- 22379802
TI  - [Influence of liquid or solid culture conditions on the volatile components of
      mycelia of Isariacateinannulata].
AB  - OBJECTIVE: To determine the volatile components of mycelia of Isaria
      cateinannulata cultured under different culture conditions, and to analyze the
      relationships between the culture conditions and volatile metabolites. METHODS:
      Mycelia were cultured in solid plates with SDAY medium and liquid shake flasks
      with SDY medium. The culture conditions were at 25 degrees C and 8 days. Volatile
      components in the mycelia of I. cateinannulata were extracted with simultaneous
      distillation extraction and analyzed by gas chromatography-mass spectrometry.
      RESULT: Alkenes, alkanes, heterocyclic and polycyclic aromatic hydrocarbons (PAH)
      were existed abundantly both in the mycelia of liquid and solid cultures, but the
      kinds and relative concentrations of the volatile components in mycelia of liquid
      and solid cultures were very different. Forty-one compounds were identified from
      the mycelia of solid culture and 32 compounds were identified from the mycelia of
      liquid culture. Esters, quinones and oximes were only found in solid cultured
      mycelia whereas carboxylic acids were only discovered in the mycelia of liquid
      culture. At the same time, mycelia of liquid culture contained much more phenols.
      The most abundant compounds in mycelia of liquid and solid cultures were
      hydrocarbons. The volatile extracts of solid cultured mycelia contained 57.6%
      alkenes and 9.19% alkanes. The volatile extracts of liquid cultured mycelia
      contained 7.85% alkenes and 22.4% alkanes. CONCLUSION: Liquid or solid culture
      conditions influenced the volatile components of mycelia of I. cateinannulata.

PMID- 22379803
TI  - [Comparison of growth models of Listeria monocytogenes in chilled pork].
AB  - OBJECTIVE: To investigate the growth of Listeria monocytogenes (LM) in chilled
      pork at four temperature and to evaluate the accuracy of three predictive models-
      GP (Growth Predictor), PMP (Pathogen Modeling Programme) and CP (ComBase
      Predictor) in predicting LM growth in chilled pork. METHODS: LM growth in chilled
      pork at 4 degrees C, 8 degrees C, 12 degrees C and 16 degrees C were determined
      by plate counting. The growth data were fitted by DMFit software to calculate
      related growth parameters: lag phase duration (LPD), growth rate (GR) and maximum
      population density (MPD). The observation values and predictions of the three
      different models were compared. RESULT: LM grew into exponential phase after 2.6
      hours of adaptation at 16 degrees C. A four- degree increase from 8 degrees C to
      12 degrees C doubled GR from 0.017 log(cfu/g) h(-1) to(0). 038 log(cfu/g) h(-1)).
      Over the temperature span from 4 degrees C to 16 degrees C, GR values predicted
      by PMP were lower than observations, while those of LPD higher than observations.
      At temperature above 8 degrees C, LPD values predicted by GP were higher than
      observations. Of three predictive models, GP prediction of GR was the best,
      though slightly higher than observations, with the bias factor (B(f)) at 1.01 and
      accuracy factor (A(f)) at 1.38, while CP was nearest to observations for LPD
      prediction, but still with high values of A(f) and B(f) (4.33 and 2.83
      respectively). CONCLUSION: It is of utmost importance to control temperature in
      chilled pork production and distribution. Because of the conservative but unsafe
      predictions, PMP model is not suitable for prediction of LM in chilled pork. We
      suggest to use GP for GR prediction. CP may be used to predict LPD as a
      reference, but with caution.

PMID- 22379804
TI  - [Comparison of concentration of volatile fatty acid and microbiota in faeces
      between healthy and diarrhoeal piglets].
AB  - OBJECTIVE: To compare volatile fatty acid (VFA) concentration and microbiota in
      faeces between healthy and diarrhoeal piglets. METHODS: Fecal samples from
      healthy and diarrhoeal piglets were collected. VFA concentration was determined
      by GC analysis. Total bacterial DNA was extracted and used for molecular analysis
      of microbiota. RESULTS: As compared to healthy piglets, the concentration of
      acetate in feces of diarrhoeal piglets tended to increase, while branched chain
      fatty acid (BCFA) decreased significantly (p < 0.05), total VFA (TVFA),
      propionate and butyrate tended to decrease. The ratio of acetate to TVFA in
      faeces of diarrhoeal piglets was significantly higher than that in healthy
      piglets (p < 0.05), while the ratio of propionate and BFVA to TVFA decreased
      significantly after diarrhoea (p < 0.05). DGGE analysis of total bacterial
      community and Clostridium cluster IV group showed no significant changes in both
      bacterial community were found in faeces of piglets after diarrhoea. Similarity
      analysis of DGGE profiles revealed that faecal samples of diarrhoeal piglets
      tended to gather in the same cluster. Real-time PCR results showed that as
      compared to healthy piglets, the 16S rRNA gene copies of total bacteria and
      Clostridium cluster IV decreased significantly in faeces of piglets after
      Diarrhea (p < 0.05), while there was no significant change in the numbers of E
      coli and Lactobacilli. CONCLUSION: VFA composition in faeces of diarrhoeal
      piglets changed accompanying with the shift of microbiota as compared to healthy
      piglets.

PMID- 22379805
TI  - [Correlation of bacterial diversity in rot Chinese cabbage with the habitat].
AB  - OBJECTIVE: To investigate the diversity of bacteria in soft rot Chinese cabbage
      and analyze their correlation with rhizosphere bacteria, we analyzed the
      bacterial population structures of soft rot Chinese cabbage and the rhizosphere
      in different habitat. METHODS: Based on the initial medium and artificial Chinese
      cabbage medium, we isolated the bacteria from soft rot tissues and rhizospheric
      soils from two typical habitats. According to the analysis of 16S rRNA gene
      sequence homology, we identified the isolated strains and analyzed the strains
      population structure. RESULTS: The total bacteria in soft rot tissues were 4.0 x
      10(8) cell g(-1) and 1.2 x 10(11) cell g(-1), the number of pure strains were 56
      and 85, the dominant strains were Curtobacterium flaccumfaciens pv.
      flaccumfaciens and Pseudomonas spp. (P. hibiscicola, P. taiwanensis, P.
      tuomuerensis, P. mosselii). The total bacteria in rhizospheric soils were 2.7 x
      10(5) cell g(-1) and 6.2 x 10(7) cell g(-1), the number of pure strains were 36
      and 70, the dominant strains were Bacillus megatherium and Pseudomonas spp. (P.
      plecoglossicida, P. hibiscicola, P. parafulva, P. monteilii, P. geniculata).
      CONCLUSION: The methods used in this study were effective in analyzing bacterial
      diversity in soft rot Chinese cabbage and the results correlated well with the
      soil bacteria analysis, suggesting that soft rot Chinese cabbage may be induced
      by various environmental bacteria. Our results infer that soft rot of Chinese
      cabbage might be pathogen-complex, and provide the clues for the mechanism study
      and protection.

PMID- 22379806
TI  - [Isolation and identification of a heterotrophic nitrifying and aerobic
      denitrifying Acinetobacter sp. YF14 and its denitrification activity].
AB  - OBJECTIVE: We separated, screened and identified a heterotrophic nitrifying and
      aerobic denitrifying bacterium from the surface sediment of a culture pool.
      Furthermore, we studied the role it plays in denitrification. METHODS: We
      separated the bacterium through enrichment culture, identified it by observing
      its morphological characteristics, studying its physiological and biochemical
      properties and making phylogenetic analysis of its 16S rDNA sequences. Then we
      studied the growth curve by regularly measuring the OD600 value, studied the
      influencing factors and optimum conditions of denitrification through orthogonal
      experiment, and examined its denitrification activity through interaction with
      the activated sludge of sewage treatment plant. RESULTS: The strain was
      identified as Acinetobacter and named A. sp. YF14, which is the first known
      Acinetobacter that carries out heterotrophic nitrification and aerobic
      denitrification. It reached the logarithmic growth phase after 12 hours, the
      stationary phase after 22 hours, and the decline phase after 45 hours. Using
      strain YF14 in a reactor under heterotrophic conditions, the NH+-N and total
      nitrogen removal rates reached 92% and 91% respectively within 3 days. In
      addition, nitrate and nitrite nitrogen were not observed during the incubation.
      Under aerobic incubation conditions, almost all of the nitrogen was removed
      through denitrification in the nitrate or nitrite culture medium inoculated with
      strain YF14. The orthogonal experiment results indicated that the denitrification
      effect was optimal when the rotate speed, carbon source, inoculation percentages,
      carbon nitrogen ratio and pH were 160 r/min, glucose, 1% , 8: 1 and 6. 5,
      respectively. Sorting Order of the factors on the denitrification effect was
      rotate speed > inoculation percentages > carbon source > carbon nitrogen ratio >
      pH. The strain YF14 could improve the denitrification rate by about 30% when
      interacting with active sludge. CONCLUSION: The strain YF14 coupling of
      heterotrophic nitrification and aerobic denitrification is feasible and is of
      practical value in water treatment.

PMID- 22379807
TI  - [Construction of the XZ113 delta eaeA, XZ113 delta stx2 and XZ113 delta ehxA
      mutants of STEC O18 XZ113 and their pathogenicity in mice].
AB  - OBJECTIVE: To study the contribution of virulence genes of STEC O18 XZ113 isolate
      to the pathogenicity in mice. METHODS: The eaeA, stx2 and ehxA knock-out mutants
      of STEC strain XZ113 were generated using lambda-Red recombination system.
      RESULTS: Bacterial adherence test showed that the eaeA mutant adhered to HEp-2
      cells in a diffuse manner with no microcolony formation. Vero cells assay showed
      that the stx mutant had no cytotoxicity to Vero cells. Enterohemolytic activity
      test showed that the ehxA mutant lost the ability to express the enterohemolytic
      activity. Competition assay between the wild-type strain XZ113 and its mutants in
      vivo and in vitro showed that all mutants were mildly attenuated in vitro, but in
      vivo, XZ113 delta eaeA was moderate attenuated, XZ113 delta stx2 and XZ113 delta
      ehxA were all highly attenuated. CONCLUSIONS: These results indicate that the
      virulence factors encoded by the stx2 and ehxA genes were important for the
      pathogenesis of STEC O18 in mice.

PMID- 22379808
TI  - [Effect of YXXM motif on viral replication of subgroup J avian leukosis virus].
AB  - OBJECTIVE: It was reported that subgroup J avian leukosis virus strain NX0101
      activates PI3K/Akt pathway during early infection in DF-1 cells. Whether there is
      YXXM motif in the amino acid sequence of NX0101 and the function of YXXM motif
      were studied. METHODS: The presence of internal transmembrane domains in the
      envelope protein of NX0101 was analyzed by Tmpred. Point mutation was introduced
      to change the YXXM motif in the NX0101 strain to FXXA. The plasmid containing the
      full genome of NX0101 with mutation within the YXXM motif in pMD18-T vector was
      constructed and transfected into DF-1 cells. Viral replication levels of NX0101
      strain and the mutation one were tested and compared by real-time PCR and ELISA.
      RESULTS: The amino acid sequence of NX0101 strain had one YXXM motif (amino acids
      554-557) in the cytoplasmic tail of envelope protein. The mutated NX0101 strain
      (Y554F, M557A) was rescued by reverse genetics technique. Viral replication of
      the mutated NX0101 strain was significantly lower than that of NX0101 strain in
      the level of either RNA or protein synthesis. CONCLUSION: The results revealed
      that the (Y)XXM motif was important for virus NX0101 replication in DF-1 cells.

PMID- 22379809
TI  - [Influence of aflatoxin on Vibrio fischeri luminescence].
AB  - OBJECTIVE: In the present study, we aim to evaluate the inhibitory effect of
      aflatoxin on Vibrio fischeri luminescence. METHODS: V. fischeri culture is
      treated with aflatoxin or the culture broth of aflatoxin-producing strains, and
      the luminescence intensity of V. fischeri is detected to analyze the influence of
      aflatoxin on V. fischeri. RESULTS: The logarithmic value of aflatoxin
      concentration and the decrease ratio of V. fischeri luminescence is in a linear
      relationship. Based on the regression equation between aflatoxin concentration
      and luminescence decrease of V. fischeri, the toxin-producing status of different
      microbes can be detected quickly and exactly: all of six tested Aspergillus
      flavus strains show toxigenicity to V. fischeri, and their toxin yield reached
      14.94 mg/L - 46.45 mg/L (represented by aflatoxin concentration), while the
      tested Aspergillus oryzae shows no toxigenicity. CONCLUSION: The above data
      showed that the luminescence change of V. fischeri could exactly reflect the
      capability of various microbes to produce toxin (especially aflatoxin), which
      provided a new clue for rapid detection of aflatoxin in industrial and
      agricultural production and could be developed as a potential method for
      aflatoxin assay.

PMID- 22379810
TI  - [Screening of three novel antimicrobial peptides with antifungal pathogens].
AB  - OBJECTIVE: In order to discover novel antimicrobial peptides against important
      crop pathogens, we designed and screened a high capacity random peptide library
      and isolated a number of clones expressing peptides with antifungal activity. We
      selected 96 peptides from the library and synthesized their sequence, which were
      used to assay their activity against crop fungal pathogens. METHODS: Using agar
      diffusion assay, these peptides were assayed for their activity against pathogens
      that cause cotton Fusarium wilt (Fusarium f. sp, vasinfecum), cotton red rot
      (Fusarium moniliforme), wheat spot blotch (Bipolaris sorokiniana) and potato
      early blight (Alternaria solani). RESULTS: The three random peptides, A6, D4 and
      F10, showed the strongest activity against the above four crop fungal pathogens.
      Through Blastp analysis, we did not find they have homologous sequences with
      known antimicrobial peptides. CONCLUSION: The novel antimicrobial peptides will
      provide gene resources for preventing important crop pathogens.

PMID- 22379811
TI  - [Schistosomiasis status in People's Republic of China in 2010].
AB  - This annual report overviewed the national endemic status of schistosomiasis
      japonica in People's Republic of China in 2010. By the end of 2010, a total of
      325 824 cases of schistosomiasis japonica were estimated with a decrease rate of
      10.92% compared to those in 2009. A total of 43 acute cases were reported,
      decreased by 44.16% compared to those in 2009. A total of 25 115 advanced cases
      were treated in 2010, increased by 3.43% compared to that in 2009. About 373
      596.18 hm2 of areas infested with Oncomelania snail were found in 2010, and about
      1 081.80 hm2 newly detected areas were reported. A total of 1 476 606 cattle were
      raised in schistosomiasis transmission regions in 2010. The infection rate of
      cattle infected with Schistosoma japonicum was 1.04% in 2010, with a little
      increase comparing to that in 2009 (1.03%).

PMID- 22379812
TI  - [Studies on resistance of Schistosoma to praziquantel XIII resistance of
      Schistosoma japonicum to praziquantel is experimentally induced in laboratory].
AB  - OBJECTIVE: To investigate the possibility of the emergence of praziquantel
      resistance in Schistosoma japonicum in Mainland China under drug pressure.
      METHODS: S. japonicum cercaria were released from the infected Oncomelania
      hupensis snails collected from the marshland in Hunan Province that was endemic
      for schistosomiasis japonica and raised in the laboratory of Jiangsu Institute of
      Parasitic Diseases, and mice were infected. O. hupensis snails were infected with
      miracidia hatched from the schistosome mature eggs that were isolated from the
      liver of the infected mice. The life cycles of a field isolate and a laboratory
      passage isolate of S. japonicum were established in laboratory via the cycle of
      mouse-snail. The mice were infected with 40 cercariae each, 35 days later post
      infection, were grouped randomly into control and resistance-induced groups. All
      the mice in the control group were sacrificed on day 45 post-infection, and any
      adult S. japonicum worms in the hepatic and portomesenteric veins were recovered
      and counted, and the worm burdens were calculated. The mice in the resistance
      induced group were administered orally with the sub-curative dose of
      praziquantel, and were sacrificed 22 days post-treatment. Any adult S. japonicum
      worms in the hepatic and portomesenteric veins were recovered and counted, and
      the worm burdens and reduction in the worms recovered which were obviously caused
      by the praziquantel treatment were calculated. The eggs in the liver of the mice
      in the resistance-induced group were isolated and hatched to yield miracidia, and
      then the snails were again infected with the newly hatched miracidia to complete
      the first-passage inducement. After raising in laboratory at 25 degrees C for 60
      70 days post-infection, the infected snails were isolated and shed cercaria, and
      the mice were infected with the newly released cercaria to start a new passage of
      resistance-inducement. The oral dose of praziquantel for the first-passage
      inducement was 100 mg/kg, and an additional 100 mg/kg was given every 2-3
      passages. The mice were infected with cercariae of the parasite with 8-passge
      resistance-inducement and the isolate that was not induced, and 35 days post
      infection, were administered with praziquantel at a single oral doses of 300
      mg/kg and 600 mg/kg respectively. All the mice were sacrificed 14 days post -
      treatment, and any adult S. japonicum worms in the hepatic and portomesenteric
      veins were recovered and counted, and the reductions in the worm burdens were
      calculated to assess the sensitivity of praziquantel in the parasites after 8
      passage resistance-inducement. RESULTS: Two isolates of Jiangsu laboratory
      passage of Jiangsu and field isolate of Hunan were established in the laboratory,
      and a total 8-passage resistance -inducement was completed. For the laboratory
      passage isolate, the worm burden reduction was 22.3% post-treatment with 100
      mg/kg praziquantel during the first-passage inducement, and 53.7% post-treatment
      with 300 mg/kg praziquantel during the 8-passage inducement, appearing that the
      worm burden reduction increased with the increasing dose of praziquantel. For the
      field-collected isolate, the worm burden reduction was 66.8% post-treatment with
      100 mg/kg praziquantel during the first-passage inducement, and 20.6% post
      treatment with 300 mg/kg praziquantel during the 8-passage inducement, indicating
      that the worm burden reduction markedly decreased with the increasing dose of
      praziquantel. The worm burden reductions were 71.5% and 97.4% respectively for
      the mice infected with the non-induced laboratory passage isolate, while
      administered with praziquantel at doses of 300 mg/kg and 600 mg/kg respectively.
      After 8-passage treatment with sub-curative praziquantel, the corresponding worm
      burden reductions decreased to 32.6% and 68.1%, respectively. For the field
      collected isolate without inducement, the worm burden reductions in the mice were
      70.8% and 97.5% respectively post-treatment with praziquantel at doses of 300
      mg/kg and 600 mg/ kg respectively, and the corresponding worm burden reductions
      decreased to 45.7% and 61.9%, respectively after 8-passage treatment. COCLUSIONS:
      S. japonicum (strain of Mainland China) is able to develop resistance to
      praziquantel under continuous drug pressure. However, there are variations in the
      potential of the emergence of resistance due to various susceptibility of
      praziquantel among different isolates. The successful establishment of
      praziquantel-resistant strain of S. japonicum (Mainland China) will provide the
      basis for exploring the mechanism of praziquantel resistance in S. japonicum, and
      developing related techniques to detect and monitor praziquantel resistance.

PMID- 22379813
TI  - [Studies on resistance of Schistosoma to praziquantel XIV experimental comparison
      of susceptibility to praziquantel between PZQ-resistant isolates and PZQ
      susceptible isolates of Schistosoma japonicum in stages of adult worms, miracidia
      and cercariae].
AB  - OBJECTIVE: To investigate the changes of sensitivity to praziquantel (PZQ) about
      PZQ-resistant isolates of Schistosoma japonicum established in laboratory by
      means of the resistance-inducement method during the stages of adult worms,
      cercariae and miracidia, so as to provide the basis for establishing the
      sensitivity-detecting technique to praziquantel. METHODS: A Jiangsu laboratory
      maintaining isolate and a Hunan field-collecting isolate of S. japonicum that
      were never treated with PZQ were as PZQ-susceptible isolates, and two PZQ-induced
      isolates that were established via drug-treated passage in laboratory were as PZQ
      resistant isolates. Mice were infected with S. japonicum cercariae collected from
      above four isolates each. Thirty-five days after the infection, the mice were
      divided into 6 groups and administered orally with PZQ at dosages of 0, 37.5, 75,
      150, 300 mg/kg and 600 mg/kg, respectively. All the mice were sacrificed two
      weeks after the treatment, and all the adult worms in the hepatic and
      portomesenteric veins were recovered and counted. The mean worm burden and
      reductions were calculated and input into Graphpad Prism 5.0 software, and the
      PZQ ED50 values of four isolates were calculated by the software. The cercariae
      of above four isolates were exposed to 10(-5), 5 x 10(-6), 10(-6), 5 x 10(-7),
      10(-7) mol/L PZQ solutions for 20, 40, 60, 80, 100 min and the changes of tail
      shedding were observed under a dissecting microscope, then the tail shedding
      rates of cercariae were calculated. The miracidia of above four isolates were
      exposed to 5 x 10(-6), 10(-6), 5 x 10(-7), 10(-7) mol/L PZQ solutions for 1, 3
      and 5 min and the morphological changes were observed under a dissecting
      microscope, then the morphological change rates of miracidia were calculated.
      RESULTS: The PZQ ED50 values of PZQ-susceptible and PZQ-resistant isolates of
      Jiangsu were 147.7 mg/kg and 565.5 mg/kg, respectively, and the PZQ ED50 values
      of PZQ-susceptible and PZQ-resistant isolates of Hunan were 151.8 mg/kg and 467.2
      mg/kg, respectively. When the cercariae were exposed to 10(-5) mol/L PZQ solution
      over 20 min, the tail shedding rate of cercariae from PZQ-susceptible isolate of
      Jiangsu was 68.8%, and the tail shedding rate of cercariae from PZQ-resistant
      isolate of Jiangsu was 38.2% (P < 0.01). When the cercariae were exposed to 10(
      7) mol/L PZQ solution over 100 min, the tail shedding rate of cercariae from PZQ
      susceptible isolate of Jiangsu was 15.9%, and the tail shedding rate of cercariae
      from PZQ-resistant isolate of Jiangsu was 6.7% (P < 0.01). When the cercariae
      were exposed to 10(-5) mol/L PZQ solution over 20 min, the tail shedding rates of
      cercariae from PZQ-susceptible isolate of Hunan was 59.4%, and the tail shedding
      rates of cercariae from PZQ-resistant isolate of Hunan was 54.6% (P < 0.05). When
      the cercariae were exposed to 5 x 10(-7) mol/L PZQ solution over 40 min, the tail
      shedding rates of cercariae from PZQ-susceptible isolate of Jiangsu was 34.3%,
      and the tail shedding rates of cercariae from PZQ-resistant isolate of Jiangsu
      was 18.4% (P < 0.01). When the miracidia were exposed to 5 x 10(-7) mol/L and 10(
      7) mol/L PZQ solutions for 1, 3 and 5 min respectively, the morphological change
      rates of miracidia from PZQ-susceptible isolates of Jiangsu and Hunan were
      significantly higher than those of PZQ-resistant isolates (P < 0.01).
      CONCLUSIONS: PZQ-resistant isolates of S. japonicum has been established in mice
      with sub-curative doses of PZQ by artificial selection in laboratory, and their
      sensitivities to PZQ are significantly lower than those of the isolates never
      treated with PZQ. The drug-resistance could exhibit in the stages of adult worms,
      cercariae and miracidia. The PZQ ED50 value of adult worms, the tail shedding
      rates of cercariae and the morphological change rates of miracidia as
      quantitative indicators can be used for monitoring the S. japonicum sensitivity
      to PZQ.

PMID- 22379814
TI  - [Surveillance of schistosomiasis in a national, surveillance site of Dantu
      District, Zhenjiang City, 2005-2009].
AB  - The surveillance of schistosomiasis in Sanzhou Village, a national
      schistosomiasis surveillance site, in Gaoqiao Town of Dantu District, Zhenjiang
      City from 2005 to 2009 showed that the schistosomiasis morbidity remained in a
      low level in the surveillance site; however, the Oncomelania snails and infected
      snail areas remained high. It is suggested that, in addition to snail control,
      comprehensive control measures should be strengthened, and the causes of infected
      snails in marshland should be investigated, so as to clarify the roles of various
      hosts in transmission of schistosomiasis.

PMID- 22379815
TI  - [Burden of disease in schistosomiasis japonica III household socioeconomic
      determinants of chronic schistosomiasis].
AB  - OBJECTIVE: To explore the socioeconomic determinants of chronic schistosomiasis
      japonica at household level. METHODS: The socioeconomic status of case and
      control families in lake and marsh schistosomiasis endemic areas were
      investigated by questionnaire, socioeconomic factors were analyzed by the
      principle components analysis, and the wealth index were calculated to evaluate
      the economic status at household level. Then the relation between schistosome
      infection and some influencing factors were analyzed by two-level Logistic
      regression model. RESULTS: A total of 2 716 households in 91 villages were
      investigated, among which 1 050 were case families and 1 666 were control
      families. The values of the first eigenvector of stone/brick house, house with >
      or = 2 floors, black/white TV, colour TV, washing machine, refrigerator, side
      occupation were -0.42, 0.46, -0.45, 0.46, 0.32, 0.24 and 0.16, respectively,
      which suggested that the first eigenvector was the comprehensive index reflecting
      family wealth. The results of Logistic regression model showed that there were 4
      household factors significantly relating to chronic schistosomiasis, namely, the
      distance from residence to schistosome-infested water, source of washing water,
      economic status, and wet land area per capita, among which the factor that the
      distance from residence to schistosome - infested water < 100 m with the highest
      (OR = 12.590, P = 0). CONCLUSION: In the lake and marsh endemic areas, health
      education and other intervention to the poor family living along river or lake
      without safe water supply should be strengthened to control schistosomiasis.

PMID- 22379816
TI  - [Strategy of comprehensive control for schistosomiasis and its effect in key
      areas of Jiangsu Province].
AB  - OBJECTIVE: To evaluate the effect of comprehensive control for schistosomiasis in
      key areas of Jiangsu Province. METHODS: The basic data and the data of
      implementation of comprehensive control measures were collected from the key
      areas of Jiangsu Province, including 30 townships, 87 marshlands and 78 anchor
      points. A field survey was carried out to investigate the Oncomelania snail
      status by using the systematic sampling method and schistosomiasis morbidity in
      humans and animals in the 12 key counties (districts). The changes of snail
      status and morbidity of humans and animals were statistically analyzed in key
      counties (districts) where comprehensive control measures was implemented, and
      the effects of schistosomiasis control before and after the implementation of the
      comprehensive control were compared. RESULTS: From 2008 to 2010, a total of 84
      100 harmless latrines were constructed, 339 600 persons were examined, 2.6938
      million people received health education, 112 000 protective creams and 798 000
      publicity materials were allocated, 9 085 domestic animals were reared in pens,
      11 800 domestic animals were examined, 130 high-risk cattle were eliminated in 30
      key townships of 12 countries (districts), Jiangsu Province. A total of 19 640.78
      hm2 were controlled with molluscicides, 798 warning tablets were placed, 116.07
      hm2 of farmlands were ploughed up and planted, 306.80 hm2 were dug for fish
      culture, and 506.74 hm2 were planted with trees for snail control in 87 high-risk
      marshlands. A total of 118.83 million Yuan were invested into the water resources
      development projects, 39.82 km-long rivers were dredged, 70.04 km-long bank were
      concreted, 30 culvert gates were re-constructed, and 22 snail sedimentation tanks
      were built. In the 78 anchor points, 95 harmless public toilets were built, 3 192
      stool container were allocated, 28 700 boatmen were examined, 71 600 protective
      creams and 53 200 publicity materials were allocated, and 46 600 persons received
      health education. Following the implementation of comprehensive control, the
      settings with infected snails, infected snail areas, infection rates of snails
      reduced from 75, 802.73 hm2 and 0.10% before the comprehensive control in 2007 to
      all 0 in 2010, with reduction rates of all 100%. The infection rates of
      schistosome in both humans and domestic animals appeared declining trends in 12
      counties (districts) from 2005 to 2010, and the human infection rates were 0.16%,
      0.04%, 0.02%, 0.02%, 0.01% and 0.01%, respectively, while being 0.11%, 0.05%, 0,
      0, 0 and 0, respectively in domestic animals. During the period of comprehensive
      control, totally 45 transmission-controlled townships and 183 villages were newly
      added. In 2010, all of the 12 counties (districts) reached the criteria of
      schistosomiasis transmission control. CONCLUSIONS: The comprehensive control with
      emphasis on the key areas where infected snails are found, is an effective
      measure to further facilitate schistosomiasis control and rapidly control the
      transmission of schistosomiasis.

PMID- 22379817
TI  - [Risk factors of schistosomiasis transmission in marshland and lake regions in
      midstream of Yangtze River].
AB  - OBJECTIVE: To study the risk factors of schistosomiasis related to household
      economic condition and individual behavior in marshland and lake regions, so as
      to provide evidences for schistosomiasis control. METHODS: Six villages were
      sampled with the stratified cluster sampling method, 2 339 villagers from 1 247
      households were surveyed by a questionnaire and meanwhile their sera were assayed
      for schistosomiasis by IHA. The Logistic regression was used to analyze the
      relationship between the results of serological examinations and risk factors.
      RESULTS: The Logistic regression model fitted well (R2 = 0.598 4) and it
      indicated that there existed a regressive relationship between the antibody
      positive rate and the endemic situation of village, family economic status, age,
      education level and infection history of schistosomiasis. CONCLUSION: Suitable
      measures should be made in according to the local economic situation, endemic
      type and population to control the transmission of schistosomiasis effectively.

PMID- 22379818
TI  - [Evaluation on application of common diagnosis methods for schistosomiasis
      japonica in endemic areas of China. III. Analysis and evaluation of
      underestimation of prevalence of Schistosoma japonicum infection by routine Kato
      Katz technique].
AB  - OBJECTIVE: To understand the rates of underestimation of Schistosoma japonicum
      infection by Kato-Katz technique with different stool samples and different
      smears in field site. METHODS: With 27 Kato-Katz thick smears (3 stool samples
      with 9 thick smears each) for 3 consecutive years as a "gold standard", the rates
      of underestimation of schistosome infection by Kato-Katz technique with different
      stool samples and different smears were evaluated in a schistosomiasis endemic
      village. RESULTS: The examined rates of schistosome infection increased and the
      rates of underestimation decreased gradually with the increase of the number of
      Kato-Katz thick smears examined. The rates of underestimation of 3 smears were
      40.98%-50.80% and the rates of underestimation of 6 smears were 25.48%-32.39%.
      The rates of schistosome infection based on the reading of 27 Kato-Katz thick
      smears were 10.96% in 2008, 8.54% in 2009 and 3.73% in 2010 respectively, but the
      rates of underestimation of various Kato-Katz thick smears were similar. There
      were no significant differences among the readings of 3, 6, and 9 smears of 1
      stool sample, 3, 6 and 9 smears of 3 stool samples, 6 smears of 2 stool samples,
      6 smears of 1 stool sample, and 6 smears of 3 stool samples. CONCLUSIONS: In a
      community with low-intensity of schistosome infection, the rate of
      underestimation is big by Kato-Katz technique with the reading of 3 smears of 1
      stool sample. It suggested that it is better to increase smears rather than the
      number of stool samples examined.

PMID- 22379819
TI  - [Effects of Schistosoma 22.6 kDa/26 GST molecule mixed with Sepharose 4B beads on
      induction of CD4+CD25+ regulatory T cells].
AB  - OBJECTIVE: To study the responses of regulatory T cells induced by Sepharose 4B
      beads mixed antigen. METHODS: Mice were immunized with different dosages of
      antigens, and the proportions of regulatory T cells were examined by flow
      cytometry. The 3H-thymidin incorporation method was used to detect the inhibitory
      function of Tregs. In vitro, dendritic cells were pulsed with different antigens.
      The expressions of MHC II, CD40, CD80/86 molecules on dendritic cells and the
      proportions of regulatory T cells were examined by flow cytometry. The 3H
      thymidin incorporation method was used for the determination of Tregs function.
      RESULTS: Compared with control groups, the proportion of regulatory T cells in
      mice immunized with Sepharose 4B beads mixed antigen was(11.48 +/- 4.12)%, and
      the difference was significant (P < 0.05). The inhibition of regulatory T cells
      in mice immunized with Sepharose 4B beads mixed antigen showed a stronger
      potential (cpm was 720 +/- 180.4). Meanwhile, the proportions of regulatory T
      cells were (17.0 +/- 80.57)% and (30.14 +/- 3.62)% when the CD4+ T cells were co
      cultured with dendritic cells pulsed with Sepharose 4B beads mixed rSj22.6/26GST
      and OVA, respectively. CONCLUSION: Sepharose 4B beads mixed antigen could induce
      the regulatory T cells in vivo and in vitro.

PMID- 22379820
TI  - [Expression and characterization of recombinant Sj23HD-HSA fusion protein in
      Saccharomyces cerevisiae].
AB  - OBJECTIVES: To prepare the fusion protein of large hydrophilic domain of 23 kDa
      membrane protein of Schistosoma japonicum and the mature peptide of human serum
      albumin (Sj23HD-HSA) and investigate its immunoreactivity. METHODS: A fusion
      protein gene encoding Sj23HD-HSA fusion protein was prepared by overlapping PCR,
      which was confirmed by TA cloning and DNA sequencing. The fusion gene of Sj23HD
      HSA was directionally subcloned into yeast expression plasmid pWX530 to construct
      a recombinant plasmid Sj23HD-HSA/pWX530. The transformants of Saccharomyces
      cerevisiae containing the recombinant plasmid Sj23HD-HSA/pWX530 were screened on
      leu deficient SD medium after yeast competent cells were transformed with
      recombinant plasmid. The excretive Sj23HD-HSA protein was expressed by culturing
      the yeast transformants at 30 degrees C for 1 week, and the protein component of
      culture supernatant was analyzed by SDS-PAGE. Sj23HD-HSA fusion protein was
      purified through Ion Exchange Chromatography. The immunoreactivity of recombinant
      Sj23HD-HSA fusion protein was determined by Western blotting with sera of
      schistosomiasis, clonorchiasis and healthy. RESULTS: The gene encoding the Sj23HD
      HSA fusion protein was constructed successfully, which was confirmed by DNA
      sequencing. The yeast transformants containing plasmid Sj23HD-HSA/pWX530 could
      express the excretive Sj23HD-HSA fusion protein without inducing. The results of
      Western blotting indicated Sj23HD-HSA could be recognized by the sera of
      schistosomiasis, but could not be recognized by the sera of clonorchiasis and
      healthy respectively. CONCLUSIONS: Sj23HD-HSA fusion protein with good immune
      reactivity is prepared successfully, which will be a potential antigen for
      schistosomiasis immunodiagnosis.

PMID- 22379821
TI  - [Compliance of film-coated praziquantel tablets in schistosomiasis transmission
      controlled areas].
AB  - OBJECTIVE: To observe the compliance of film-coated praziquantel tablets in the
      schistosomiasis transmission controlled areas, so as to provide the evidence for
      the establishment of chemotherapy intervention measures in these areas. METHODS:
      In the areas of schistosomiasis transmission controlled in Sichuan Province, 234
      people were selected as film-coated praziquantel group (FCPG), and 203 people
      were selected as praziquantel group (PG). A questionnaire survey was implemented
      and the compliance of chemotherapy of the 2 groups was compared. RESULTS: In PG,
      all the people indicated that the praziquantel tablets has bad smell, 98.0% of
      the people had side-effects, such as nausea, headache, 69.5% thought the medicine
      was harmful to health subjectively, and 99.5% thought that it was too much dose
      of tablets for taking one time. In FCPG, all the people indicated that the film
      coated praziquantel tablets had no bad smell, 18.8% of the people had side
      effects, and 74.4% would like to choose film-coated praziquantel tablets. The
      rates of knowledge of praziquantel of PG and FCPG were 50.7% and 29.1%,
      respectively ( chi2 = 21.449, P = 0.01). CONCLUSIONS: The film-coated
      praziquantel tablets have no bad smell and lighter side-effects. The compliance
      of the film-coated praziquantel tablets is high in the areas of schistosomiasis
      transmission controlled, so the film-coated praziquantel tablets are worth to
      popularize and apply.

PMID- 22379822
TI  - [Impact of simulation operation high water level on Oncomelania hupensis natural
      growth in water diversion rivers of east route of South-to-North water Diversion
      Project].
AB  - OBJECTIVE: To verify the impact of operation high water level on Oncomelania
      hupensis natural growth in the water diversion rivers of the east route of South
      to-North Water Diversion Project. METHODS: The data of the daily mean water level
      were investigated in the stilling pool of Jiangdu Pumping Station during the
      water diversion under the emergency anti-drought, and the water level data of the
      previous year served as the control. The dynamic of natural growth of O. hupensis
      snails was observed before and after the high water level in the beach wetlands
      of the stilling pool of Jiangdu Pumping Station. The water level of emergency
      anti-drought was as simulation operation water level of the east route of South
      to-North Water Diversion Project in the stilling pool, and then the effects of
      operation water level on O. hupensis natural growth in the water diversion rivers
      of the east route of South-to-North Water Diversion Project were studied.
      RESULTS: The altitude of the beach wetlands was 6.4 to 7.2 meters in the stilling
      pool of Jiangdu Pumping Station. The water diversion was 255 days continuously
      and the pumped water was 6.235 billion cubic meters in the Jiangdu Pumping
      Station from November 2010 to July 2011. There were 216, 136 days and 39 days
      when daily mean water level were more than or equal to 7.2, 7.6 and 8.0 meters
      during the water diversion, respectively. The snail densities were 0.856
      snails/0.1m2 and 0.0153 snails/0.1m2, respectively, before and after the No.3
      beach wetlands flooded in the stilling pool of Jiangdu Pumping Station. The
      densities of living snails decreased by 98.21%, and there was no any progeny of
      snail. The snails were not detected in other environment of the stilling pool.
      CONCLUSION: The operation high water level can effectively restrain snail
      breeding in the water diversion rivers of the east route of South-to-North Water
      Diversion Project.

PMID- 22379823
TI  - [Surveillance of malaria epidemic situation after malaria basically eliminated in
      Wujin District, Changzhou City].
AB  - The surveillance of malaria epidemic situation after malaria basically eliminated
      in Wujin District, Changzhou City showed that the incidence of malaria fluctuated
      between 0.001 per thousand and 0.015 per thousand from 1992 to 2009. The cases
      were dispersively distributed and most of them were input cases. The current
      emphasis of eliminating malaria should be the control of input cases, anti
      malaria management of floating population, the training for clinical doctors and
      microscopists, and mass health education.

PMID- 22379824
TI  - [Effect of cultivation for snail control on schistosomiasis in Changsha urban
      section of Xiangjiang River].
AB  - OBJECTIVE: To study a reliable, friendly environmental and sustainable
      Oncomelania snail control method in marshlands of the Xiangjiang River. METHODS:
      According to the special characteristics of the marshlands of the Xiangjiang
      River, smoothing and cultivating in beaches were applied for snail control. In
      sections with scarce distribution of snails, lowering parts of 4.4 beaches and
      raising other parts were added. RESULTS: Since 2003, the project has been
      practiced for 8 years. The average snail density declined by 99.83% with the
      simple smoothing beaches and then cultivation there. The average snail density
      declined by 100% with lowering parts of beaches and raising other parts and then
      cultivation. The schistosome infection rate was 0.31% with a declined rate of
      93.84% in residents in 2006. The schistosome infection rate was 1.03% in 2010.
      The test result of water contamination was negative. CONCLUSIONS: The method of
      simple smoothing beaches and then cultivation can control the density of snails
      in marshlands and the method of lowering parts of beaches and raising other parts
      and then cultivation is more effective.

PMID- 22379825
TI  - [Experiment of praziquantel rectal administration in treatment of schistosomiasis
      in mice].
AB  - OBJECTIVE: To evaluate the efficiency of rectal administration of praziquantel in
      the treatment of schistosomiasis in mice. METHODS: Forty mice were divided into 4
      groups. Each mouse was infected with Schistosoma japonicum cercariae 40 +/- 2.
      Forty-two days after the infection, the mouse was rectally administered with
      different doses of praziquantel. In the first, second and third group, each mouse
      was given 100, 200 mg/kg, and 400 mg/kg single dose of praziquantel, and the
      fourth group was a blank control group. One week after the administration, all
      the mice were sacrificed and the worm reduction rate, reduction rate of liver
      eggs, and matching reduction rate were calculated. RESULTS The worm reduction
      rate and matching reduction rate were 57.63% and 76.60% respectively in the 200
      mg/kg group, and 49.15% and 51.06% respectively in the 400 mg/kg group, which
      were better than those in the 100 mg/kg group. CONCLUSION: Rectal administration
      of praziquantel has good efficiency in the treatment of schistosomiasis in mice;
      therefore, it provides a new option for the prevention and control of animal
      schistosomiasis.

PMID- 22379826
TI  - [Quantitative detection and species identificaton of human Plasmodium spp. by
      using SYBR Green I based real-time PCR].
AB  - OBJECTIVE: To develop a real-time PCR method for human Plasmodium spp.
      qantitative detection and species identificaton. METHODS: According to the
      sequence of Plasmodium 18S rRNA, the primer set was designed based on the genus
      specific region around the species-specfic region. The PCR products were
      amplified and cloned into pGEM-T vector to produce standard plasmids of real-time
      PCR, and melting curve analysis was conducted following real-time PCR for
      Plasmodium species indentification. RESULTS: By using the primer set, specific
      PCR products were produced from all of 4 human malaria parasites. The correlation
      of real-time PCR standard curve was good enough (r = -1.00) for quantitation.
      According to the melting curve analysis, the melting temperatures (Tm) of
      Plasmodium malariae, falciparum, ovale and vivax were significantly different,
      being 71.3, 72.8, 74.6 degrees C and 75.8 degrees C, respectively. CONCLUSION:
      The SYBR Green I based real-time PCR method developed in this study can be used
      for human Plasmodium spp. quantitative detection and species identificaton.

PMID- 22379827
TI  - [Cloning, expression and evaluation on effect in serological diagnosis of
      cysteine protease of Clonorchis sinensis].
AB  - OBJECTIVE: To clone and express the cysteine protease of Clonorchis sinensis and
      evaluate its effect on immunodiagnosis of human clonorchiasis. METHODS: Based on
      a cysteine protease gene fragment of C. sinensis (CS-CP, GenBank accession:
      AF093242), a pair of primers were designed and amplified from total cDNA of C.
      sinensis, and the gene was cloned into plasmid pPIC9K and expressed in Pichia
      pastoris GS115. The expressed product was purified. Ten BALA/c mice were
      immunized with the purified CS-CP, and the anti CS-CP antibody in the sera of
      immunized mice was tested with ELISA. Finally, its effect on serodiagnosis was
      evaluated with Dot-ELISA and Western blot. RESULTS: The CS-CP gene (approximately
      927 bp) was successfully amplified, cloned and expressed in Pichia pastoris
      GS115. The sera of mice immunized with purified rCS-CP could be recognized by the
      soluble antigen of C. sinensis adult worms and its special anti CS-CP antibody
      titer was high (1: 64 000). The rCS-CP was probed by Dot-ELISA and Western-blot
      with sera from patients with clonorchiasis and other parasitic infections, and it
      had a sensitivity of 91.7% (55/60) in diagnosis of clonorchiasis and a specifity
      of 97.6% (82/84) for healthy population. The rCS-CP had no cross-reaction with
      the patients of schistosomiasis japonica, but had a cross-reactivity of 20.0%
      (2/10) with the patients with paragonimiasis westermani. CONCLUSIONS: rCS-CP
      possesses a favorable diagnostic effect and it is a better serodiagnostic one
      among recombinant antigens.

PMID- 22379828
TI  - [Investigation on outbreak of angiostrongyliasis cantonensis due to consumption
      of snail food in Dali City].
AB  - OBJECTIVE: To investigate the potential cause of an outbreak of eosinophilic
      meningitis in Dali City in March, 2011. METHODS: A retrospective investigation
      was performed among 18 consumers who had meal together. The clinical documents of
      inpatients were analyzed and the diagnoses were checked. The outpatients were
      investigated through a case survey. Pomacea snails on sale were examined for the
      infection status of Angiostrongylus cantonensis. RESULTS: Of 18 persons, 16
      consumed Pomacea snail food and 9 were infected with an infection rate of 56.3%.
      The two persons who did not consumed snail food were not infected. Serum samples
      of seven patients were examined for antibody to Angiostrongylus cantonensis in
      peripheral blood and 3 were proved positive (42.9%). The snails consumed by the
      patients came from the market, and the surveillance data showed that the
      infection rate of Angiostrongylus cantonensis of Pomacea snails was 7.3%.
      CONCLUSION: According to the epidemiological survey, clinical manifestations, and
      laboratory examinations, the outbreak of eosinophilic meningitis is due to the
      consumption of Pomacea snails infected with Angiostrongylus cantonensis.

PMID- 22379829
TI  - [Three schistosomiasis patients combined with acute hepatitis E].
AB  - Three schistosomiasis patients combined with acute hepatitis E were treated with
      N-acetylcysteine, ursodeoxycholic acid and traditional Chinese medicine. The
      therapeutic effect was satisfied.

PMID- 22379831
TI  - [Snail control effect of film covering method in fish ponds and ditches].
AB  - OBJECTIVE: To evaluate the snail control effect of a film covering method in fish
      ponds and ditches. METHODS: Two fish ponds and 2 ditches with Oncomelania snails
      were selected as pilots, and 1 fish pond as Group A1 and I ditch as Group B1
      received niclosamide spraying + film covering, and another fish pond as Group A2
      and another ditch as Group B2 received niclosamide spraying only. The snail
      control effects were observed at 15, 30, 90 d and 360 d after the test, and the
      fish and other aquatic were also observed. RESULTS: In Group A1, the adjusted
      mortality rates of snails were 92.31%, 99.36% and 100% at 15, 30 d and 90 d after
      the test, respectively; in Group B1, the adjusted mortality rates of snails were
      91.45%, 95.84% and 100% at 15, 30 d and 90 d after the test, respectively; and
      there was no death of fish. The densities of snails were 0 and 0.07 snails/0.1 m2
      one year after the test, respectively. In Group A2, the adjusted mortality rates
      of snails were 75.36%, 72.59% and 65.76% at 15 d, 30 d and 90 d after the test,
      respectively; in Group B2, the adjusted mortality rates of snails were 70.36%,
      72.87% and 75.82% at 15, 30 d and 90 d after the test, respectively; and there
      was death of fish. The densities of snails were 0.11 snails/0.1 m2 and 0.13
      snails/0.1 m2 one year after the test, respectively. CONCLUSION: In ponds and
      ditches with snails, the niclosamide spraying + film covering method is very
      effective and safe.

PMID- 22379830
TI  - [Surveillance and forecast of schistosomiasis transmission in Chaohu Lake area in
      Anhui Province, 2008-2010].
AB  - OBJECTIVE: To understand the dynamic changes of the potential prevalent factors
      of schistosomiasis in Chaohu Lake area so as to provide forecast information on
      the outbreak of schistosomiasis in the area. METHODS: From 2008 to 2010, fixed
      and mobile surveillance sites in potential endemic areas of Juchao District in
      Chaohu City, which was located in the southeast side of Chaohu Lake, were
      selected, and the schistosomiasis infection situation of local people, mobile
      population and livestock were investigated by immunological assays and/or stool
      examinations. The distribution of Oncomelania snails was surveyed in risk areas
      and suspicious areas, the spreading patterns of Oncomelania snails were observed
      in rivers that directly connected with the Yangtze River, and the Oncomelania
      snails were raised in the cages on the beaches of Chaohu Lake and a control area,
      and their survival and reproduction capacity was observed. RESULTS: In 2008, a
      total of 301 local people were screened by IHA, and there were no positives. From
      2008 to 2010, a total of 321, 362 and 306 mobile population were examined by IHA,
      respectively, and the positive rate of antibody were 3.74%, 4.97% and 2.94%,
      respectively. The antibody positives were tested by stool examinations, and the
      positive rates were 66.67%, 50% and 55.56%, respectively. A total of 91 local
      livestock and 92 livestock from endemic areas were examined respectively by the
      miracidium hatching method, and there were no positives. A total of 97.8 hm2 risk
      areas and 193.62 hm2 suspicious areas in the potential endemic area were surveyed
      respectively, but no Oncomelania snails were found. The investigation results on
      snail spreading patterns indicated that snails could spread into Chaohu Lake by
      adsorbing on floating debris. The field study revealed that Oncomelania snails
      could survive and reproduce in the Lake. CONCLUSIONS: The imported infectious
      sources of schistosomiasis have been found in Chaohu Lake area, and the higher
      possibility of imported Oncomelania snails spreading into the Lake and surviving
      and reproducing in the lake is predicted. Therefore, effective measures should be
      taken to decrease the risks of schistosomiasis transmission in the potential
      endemic area.

PMID- 22379832
TI  - [Study on quality of schistosomiasis knowledge questionnaire of primary pupils in
      Wuxing Farm School of Nanchang City].
AB  - OBJECTIVE: To evaluate the quality of a questionnaire about schistosomiasis
      knowledge of the pupils in Wuxing Farm School in Nanchang City. METHODS: The
      quality of the questionnaire about schistosomiasis knowledge was evaluated
      through reliability, validity, discrimination and some other indexes. RESULTS:
      The entire reliability of the survey was high with its split-half reliability of
      0.68 and Cronbach alpha coefficient of 0.627. The content validity was good: the
      exploratory factor analysis revealed 5 common factors from 13 questionnaire items
      which could account for 58.3% of the total variance; the confirmatory factor
      analysis revealed that the construct validity of 13 questionnaire items was
      better than that of the whole questionnaire (17 items in total) (chi2 = 90.5, df
      = 65, GFI = 0.92, AGFI = 0.88, NFI = 0.58, CFI = 0.817, RMSEA = 0.049); the
      difficulty and the discrimination coefficients of the questionnaire were
      suitable, being 0.595 and 0.42 respectively. CONCLUSION: The questionnaire is
      qualified in general, but parts of the items need to be revised to perfect.

PMID- 22379833
TI  - [Therapeutic effect of dahuangzhechong pills on advanced schistosomiasis].
AB  - OBJECTIVE: To evaluate the therapeutic effect and safety of Dahuangzhechong pills
      on advanced schistosomiasis. METHODS: Sixty-two patients with advanced
      schistosomiasis were divided randomly into two groups, a treatment group and a
      control group, and treated with Dahuangzhechong pills and routine therapy,
      respectively. The course of treatment was 52 weeks in the two groups. Before and
      after the 52-week treatment, the indexes of liver function and hepatic fibrosis,
      prothrombin time (PT), Child-Pugh scores and changes of B-type ultrasonic images
      were detected for all the patients. RESULTS: There were significant differences
      in the levels of alanine aminotransferase (ALT) and total bilirubin (TBIL), the
      indexes of hepatic fibrosis, portal venous inside diameters and portal venous
      flow between the two groups after 52 weeks treatment (P < 0.05). In addition,
      there were no obvious adverse effects during the treatment in the patients of the
      Dahuangzhechong pill group. CONCLUSION: Dahuangzhechong pill treatment is a safe
      and effective therapy for the patients with advanced schistosomiasis.

PMID- 22379834
TI  - [Health education needs for malaria control in rural residents in Hai'an County].
AB  - OBJECTIVE: To understand the status of knowledge, attitudes and practices (KAP)
      and health education needs for malaria prevention and treatment of rural
      residents in Hai'an County. METHODS: Hai'an County was divided into three regions
      of east, south and north, and the primary and secondary students and residents
      were selected with the multi-stage sampling method and investigated with
      questionnaire for the status of KAP and the health education needs of malaria
      control. The results were analyzed statistically. RESULTS: The awareness rates of
      malaria transmission, symptoms, prevention knowledge in the residents were
      significantly higher than those in the students (P < 0.05). The awareness rates
      of malaria prevention knowledge in the residents had significant differences
      among the residents with different education levels (P < 0.05), and the education
      levels were positively correlated with the awareness rates of malaria prevention
      knowledge. The main ways of rural residents to get their knowledge of malaria
      control were radio, newspapers, the village doctors, public health bulletin,
      posters, students, and television caption in order; the main ways of students to
      get their knowledge of malaria control were television, newspapers, public health
      bulletin, teachers, radio, and flyers in order. CONCLUSIONS: We should pay full
      attention to the advantages of mass media to carry out the extensive health
      education on malaria prevention and control, and should also take into account
      the different characteristics of the audience.

PMID- 22379835
TI  - [Analysis of imported falciparum malaria cases of Nantong City from 2001 to
      2010].
AB  - OBJECTIVE: To analyze the characteristics of imported falciparum malaria cases of
      Nantong City in the recent ten years so as to provide the evidence for improving
      prevention and control of malaria in the future. METHODS: The data about imported
      falciparum malaria cases of Nantong City from 2001 to 2010 were collected and
      analyzed for the characteristics and distribution of the patients by the
      retrospective method. RESULTS; There were 79 imported falciparum malaria cases in
      the last 10 years. Totally 96.2% of patients were infected in Africa. Most of
      them were young people and worked for the construction services. Seasonal
      distribution difference was not obvious. CONCLUSIONS; The imported falciparum
      malaria epidemic is rising in Nantong City. Therefore, we should strengthen the
      anti-malaria health education to increase the self-protection of labors, and
      strengthen the training of medical stuff and also strengthen the monitoring of
      malaria epidemic.

PMID- 22379836
TI  - [Thought of schistosomiasis control strategy with emphasis on controlling sources
      of infection in lake and marshland endemic regions].
AB  - This paper discusses the issues and suggestions in the implementation of the new
      schistosomiasis control strategy with emphasis on controlling sources of
      infection in lake and marshland endemic regions in order to accelerate the
      implementation of the new control strategy.

PMID- 22379837
TI  - [Investigation on health workforce in county anti-schistosomiasis institutions of
      Jiangxi Province, 2010].
AB  - OBJECTIVE: To understand and assess changes of health workforce in county anti
      schistosomiasis institutions of Jiangxi Province, so as to provide the evidence
      for improving the health workforce construction. METHODS: The status of health
      workforce of county anti-schistosomiasis institutions was surveyed with self
      designed questionnaire, and the results were compared with the baseline survey
      results in 2007. RESULTS: The total number of employees was 1 384 in 2010 with
      the decrease of 71 persons compared with that in 2007. The average number of
      people per institution was 40.71, with the decrease of 0.86 per institution,
      compared with that of 2007. Compared with 2007, the employees with bachelor
      degree increased by 6.17%, those with college degree increased by 6.8%, and the
      attending rate of training and further study also increased. CONCLUSIONS: The
      health workforce has improved in county anti-schistosomiasis institutions of
      Jiangxi Province. The professional workers should be trained continually to
      improve their diathesis.

PMID- 22379838
TI  - [Surveillance of schistosomiasis in Caohui Village, Yangxin County, 2005-2010].
AB  - The surveillance of schistosomiasis in a national schistosomiasis surveillance
      site, Caohui Village, Yangxin County, 2005 - 2010 showed that the infection rates
      of residents and livestock decreased from 4.56% and 28.33% to 1.19% and 1.67%,
      respectively. However, the endemic situation was still of instability. Therefore,
      we should strengthen the comprehensive control measures including the control of
      infectious sources in the light of local conditions to control the
      schistosomiasis endemic situation.

PMID- 22379839
TI  - [Study on a new prevention and control model on soil-borne parasitic diseases in
      rural areas of China].
AB  - OBJECTIVE: To explore a new prevention and control model on soil-borne parasitic
      diseases in rural areas of China. METHODS: Eight provinces and autonomous regions
      were selected in China as demonstration areas implementing integrated control on
      soil-borne parasitic diseases. The integrated control measures included authority
      organization and harmonization, health education, deworming, and environment
      modification. RESULTS: After three years, the infection rates of soil-borne
      parasitic diseases were significantly decreased in these areas. There were three
      safe guard and organization modes, three health education modes, four mass
      worming medication modes, and two modes of water, toilet and environment changes.
      CONCLUSION: The work in the various demonstration areas was summarized which
      pointed out a new model with efficiency and local characteristics on soil-borne
      parasitic disease prevention and control.

PMID- 22379840
TI  - [Malaria endemic and control in Yangzhong City from 1979 to 2010].
AB  - In Yangzhong City, the incidence of malaria decreased gradually from 883.48 per
      hundred thousand in 1979 to 0.36 per hundred thousand in 2010. The incidence was
      0 from 2005 to 2009, but 1 local infected patient was found in 2010. The
      achievements of malaria control are significant, however, with the development of
      economy, the increase of mobile population, and the dimness of malaria control
      consciousness, the control strategy should be adjusted in order to eliminate
      malaria.

PMID- 22379841
TI  - [Discussion of laboratory diagnosis for echinococcosis].
AB  - Laboratory diagnosis is one of the main means for diagnosis of echinococcosis.
      With the continuing evolvement of immunology and immunology technology, the
      laboratory diagnosis of echinococcosis obtained an encouraging progress, and the
      sensitivity and specificity of diagnostic tests for echinococcosis further
      improved. This review summarizes the current information concerning stool test,
      diagnostic antigen, and immunological diagnostic methods of echinococcosis.

PMID- 22379842
TI  - [Surveillance of schistosomiasis of reconstruction personnel after earthquake in
      Mianzhu City from 2009 to 2011].
AB  - After "5.12" earthquake, 5 128 reconstruction people from schistosomiasis endemic
      areas were surveyed for schistosome infection from 2009 to 2001. There were 261
      seropositive persons with the positive rate of 5.09%, but there were no persons
      with positive stool examination. The seropositive rate was higher in
      reconstruction persons from schistosomiasis endemic areas than that in local
      residents, therefore, we still should strengthen the active schistosomiasis
      surveillance of reconstruction people from schistosomiasis endemic areas in order
      to prevent input of infection source so as to consolidate the achievements of
      schistosomiasis control.

PMID- 22379843
TI  - [Effect of Management Scheme on Control of Imported Falciparum malaria in
      Yangzhou City, 2010].
AB  - After 1-year implementation of Management Scheme on Control of Imported
      Falciparum Malaria in Yangzhou City, 2010, the coverage rate of health education
      was 100% in those returning from foreign countries, and the active treatment rate
      was 100%. All professional staff in medical and disease control institutions
      received training. 48.1% of the cases received standard treatment within 24 h,
      and all persons returning from foreign countries who had fever were examined for
      Falciparum infections. The cure rate was 100%, and the successful diagnosis of
      malaria in lab was 100%. It is indicated that the management scheme has an
      obvious effect on the control of imported falciparum malaria. However, health
      education among personnel of labor-exporting services and training for health
      staff should be further strengthened.

PMID- 22379844
TI  - [Surveillance of echinococcosis in high risk areas of Yixing City from 2008 to
      2009].
AB  - An investigation was conducted retrospectively for echinococcosis (hydatid
      disease) in Yixing City from 2008 to 2009, the serum or fecal samples of
      suspected patients during the past 5 years and host animals were assessed by
      ELISA. There were 2 cases reported by network and 4 confirmed patients by
      investigation, and among the total 6 cases, 5 cases may be infected in the
      locality. The positive rates were 0.52%, 0.14% and 1.08% in adults aged over 20
      years, children aged 7 to 12 years (by serum tests) and dogs (by fecal tests)
      respectively.

PMID- 22379845
TI  - [Surveillance of schistosomiasis in a national surveillance site of Yangzhong
      City, 2005-2010].
AB  - The surveillance of schistosomiasis in Shicheng Village, a national
      schistosomiasis surveillance site in Yangzhong City from 2005 to 2010 showed that
      snail areas were 16.43 hm2, the occurrence rates of frames with living snails and
      mean densities of living snails exhibited a declining trend year by year, and the
      infected snails were only found in 2007. The sero-positive rates in residents
      were 1.81%, 0.98%, 0.29%, 0.28%, 0.47% and 0.51%, respectively from 2005 to 2010.
      However, no stool-examination -positive persons were detected. During the period,
      no acute infections occurred, and no advanced cases and infected animals were
      detected. It is indicated that schistosomiasis has been effectively controlled in
      the surveillance site. However, snails remain present, so comprehensive control
      and surveillance of infectious sources should be further strengthened.

PMID- 22379846
TI  - [Surveillance of schistosomiasis after its transmission being interrupted in
      Huangshan City, 1994-2010].
AB  - In Huangshan City, schistosomiasis surveillance from 1994 to 2010 showed that
      there were no patients and livestock newly infected with schistosome, no infected
      Oncomelania snails, but the snail status was stable. It is suggested that the
      schistosomiasis control strategy with emphasis on snail surveillance is
      effective, and snail surveillance is still a key measure of schistosomiasis
      surveillance in the future.

PMID- 22379847
TI  - [Comparative analysis of surgical and medical treatment of macroprolactinoma of
      different localization].
AB  - The authors performed comparative analysis of results of primary surgical and
      medical treatment of 306 patients with macroprolactinoma. The series included 178
      male and 128 female patients. The tumor was endosellar in 48 cases,
      endosuprasellar in 94, invaded skull base in 164. The paper demonstrates that
      according to dynamics of visual function, neurological and hypopituitary
      symptoms, and probability of prolactin level normalization, treatment with
      cabergoline has significant advantages in comparison to surgery. Only surgical
      treatment of endosellar prolactinomas can compete with conservative treatment.
      After these operations no postoperative complications were observed,
      normalization of prolactin level was present in 67% of cases, and these results
      did not differ from results of medical treatment (71%). In case of extrasellar
      grown of macroprolactinoma, especially invading skull base, primary medical
      therapy is preferred.

PMID- 22379848
TI  - [Prognostic value of PET using 11C-methionine in patients with untreated cerebral
      gliomas].
AB  - We evaluated the prognostic role of positron emission tomography (PET) with 11C
      methionine in adults with untreated supratentorial glioma. Histopathologic
      grading and clinical follow-up data were available from 147 patients with low
      grade (n=74) and high-grade gliomas (n=73). Follow-up was conducted until the
      last clinical contact (n=79) or until death (n=68). The 11C-methionine uptake
      index (UI) was calculated as the tumor hot spot-to-normal cortex uptake ratio. In
      the univariate analysis the statistical support from clinical, histological, and
      PET parameters was estimated using Kaplan-Meier method and log-rank test. For all
      glioma patients age (<40 or > or = 40 years), astrocytoma histopathology and WHO
      grading class (low versus high), extent of the increased 11C-methionine uptake
      (<6 cm or > or = 6), were found to be significant predictors of survival by
      univariate analysis. For all grades of gliomas UI higher than 2.0 was
      statistically associated with a shorter survival (p=0.00001). Patient sex, glioma
      location, pattern of the 11C-methionine uptake were not significantly predictive.
      In the most patients UI was closely associated with glioma histopathology.
      However separate analysis of astrocytoma subgroups showed that PET with "C
      methionine was a more reliable prognostic factor in case of conflict between
      metabolic characteristic and histopathology findings. A high uptake of 11C
      methionine and large extent of increased 11C-methionine accumulation were
      statistically associated with a poor survival time. Results showed that PET with
      11C-methionine may be useful for determinating the prognosis of patients with
      primary glioma and this information can provide aid in making treatment decision.

PMID- 22379849
TI  - [Technique of stereotactic cryodestruction in management of patients with
      cerebral gliomas].
AB  - Aim of the study was to evaluate the safety and efficiency of stereotactic
      cryodestruction of supratentorial astrocytomas that were located deeply in the
      brain and/or within eloquent areas.We examined 74 patients aged 18-64 years with
      supratentorial gliomas of different grade located in deep or eloquent brain
      areas. All the patients underwent stereotactically guided cryodestruction of the
      tumor. The survival rate was evaluated by the Kaplan-Meier method. The chi-square
      method was used for comparative analysis of results of this study with available
      data from the literature. For the analysis of the prognostic importance of
      various factors the Cox proportional hazards model was applied. The average
      survival period was 12.4 months for glioblastoma (control group--6.4 months,
      p=0.04), and 46.9 months for anaplastic astrocytoma (control group--18 months,
      p=0.006). For patients with fibrillar-protoplastic astrocytoma the 5-year
      survival rate was 95.7%. The frequencies of complications did not exceed those of
      the routine surgical interventions in patients with brain tumors. We found that
      stereotactic cryodestruction as well the Karnofsky performance score were
      statistically reliable prognostic factors (p=0.0377 and p=0.0006, respectively),
      while the extent of cryodestruction and the residual tumor mass did not influence
      the survival rate. Stereotactic cryodestruction is a safe surgical procedure,
      which results in statistically significant improvement of survival in patients
      with supratentorial gliomas located within deep and/or eloquent areas of brain.

PMID- 22379850
TI  - [A new entity in WHO classification of tumors of the central nervous system-
      embryonic tumor with abundant neuropil and true rosettes: case report and review
      of literature].
AB  - Embryonic tumor with abundant neuropil and true rosettes (ETANTR) is a very
      aggressive rare tumor with unique histologic and molecular features occurring in
      very young children. At present approximately 80 cases of ETANTR have been
      documented in the literature since first description in 2000. We report seven
      patients with ETANTR below 4 years of age who underwent surgical resection in the
      Burdenko Neurosurgery Institute between 2005 and 2010. Four children have
      received different modality chemotherapy and radiotherapy and two patients were
      treated by chemotherapy alone. One child did not receive any adjuvant treatment.
      All children had local relapses, two of them were operated twice. A 2 year old
      girl underwent subtotal resection thrice. Histological examination showed that
      all tumors were composed of true multilayered rosettes admixed with large areas
      of paucicellular neuropil. By analysis of recurrences we have found that large
      areas of neuropil and number of true rosettes were lost and tumors acquired a
      resemblance to central nervous system primitive neuroectodermal tumors. In four
      cases frozen tumor material was available for array-based comparative genomic
      hybridization, which discovered trisomy of chromosome 2 and amplification at the
      19q13.42 chromosome locus. Fluorescence in situ hybridization revealed
      amplification at the 19q13.42 chromosome locus in all cases.

PMID- 22379851
TI  - [Hereditary cerebral cavernous malformations: analysis of 12 families].
AB  - Familial (hereditary) cerebral cavernous malformations (CCM) are rare disorders,
      they have autosomal-dominant type of inheritance. We report 12 families of non
      Hispanic descent in which 54 typical CCM were discovered. In 8 families CCM were
      identified in 2 generations, in 2 - in 3 generations. 46 lesions were
      supratentorial, 8 - subtentorial. Multiple lesions were present in 67% of cases.
      Manifestation was observed in 24 persons, including seizures in 17 and hemorrhage
      in 7. In 9 of 10 families onset of symptoms was earlier with every next
      generation. In one patient asymptomatic parietal CCM was associated with
      symptomatic posterior fossa AVM and cutaneous angioma. On the follow-up MRI
      revealed no new lesions. Surgical treatment was performed in 14 cases: in 13
      patients 15 CCM were removed, and 1 patient underwent third ventriculostomy. The
      paper discusses evaluation and management of families with symptomatic and
      asymptomatic types of disease, trends and perspectives of further investigations.

PMID- 22379852
TI  - [Ventriculoperitoneal and ventriculoatrial shunts in treatment of patients with
      brain tumors].
AB  - Two 234 patients with tumor-associated hydrocephalus underwent their first shunt
      implantation at Burdenko Neurosurgery Institute between 2004 and 2008. Age of the
      patients ranged from 18 to 77 years (mean 44). The follow-up was available in 162
      patients (72%). The median follow-up was 10 months. Shunt failure occurred in
      29,2% of 162 patients. Kaplan-Mayer analysis showed that the probability of shunt
      failure free interval was 72, 69, 60% at one, two and three years after
      insertion, respectively. The most frequent cause of shunt failure was malposition
      of the ventricular catheter (30,6%), occlusion of the ventricular and abdominal
      catheter occurred in 20,4 and 22,2%, respectively. Shunt infection was
      encountered in 24,5% of cases. Among the analyzed factors (position of the
      catheter within the ventricle, additional operations such as tumor resection,
      implantation of external ventricular drain before shunt surgery, malignancy of
      the tumor and type of hydrocephalus) only presence of external ventricular drain
      increased the risk of shunt infection. The duration of external drainage
      positively correlated with the risk of shunt infection. In most cases shunt
      failure can be prevented. The results of the study may help the surgeon to choose
      the optimal treatment strategy for patient with tumor-associated hydrocephalus.

PMID- 22379853
TI  - [Videooculography in evaluation of oculomotor function in patients with mass
      lesions of pineal region, midbrain and pons].
AB  - Aim of this study was to assess feasibility of videooculography in evaluation of
      oculomotor function and its dynamics in patients with mass lesions of pineal
      region, midbrain and pons. Computed videooculography was performed in 48 patients
      with tumors of pineal region and midbrain, 9 patients with pontine hematomas and
      10 healthy volunteers. 25 patients with midbrain and pineal neoplasms were
      followed after tumor resection or open biopsy. We evaluated amplitude of eye
      movements in normal and impaired oculomotor function. 4 grades decreases of
      amplitude upwards, downwards, medially and laterally were emphasized. In early
      postoperative period statistically significant decrease of amplitude in patients
      with clinical deterioration was observed. Application of videooculography allows
      reliable quantitative assessment of oculomotor function, registration and storage
      of examination data and follow-up of oculomotor function for observation of
      tendencies in course of disease.

PMID- 22379854
TI  - [Five-component visual analogue scale for assessement of pain status
      retrospective analysis of outcomes after surgical treatment of degenerative spine
      disease].
AB  - The study was performed for development of more precise criteria for assessment
      of pain using five-component visual analogue scale. Pain status was studied in
      493 patients who underwent lumbar spinal nerve root decompression. Pain scale
      included the following parameters: pain at the moment, usual pain, maximal pain,
      minimal pain and overall pain score which was calculated as an average quantity
      of the previous four parameters. Overall pain score is a more precise criterion
      for evaluation of postoperative pain status in patients with degenerative lumbar
      spine disease.

PMID- 22379855
TI  - [Endoscopically assisted removal of posterior fossa meningioma combined with
      microvascular decompression of trigeminal nerve root (early experience)].
AB  - The article presents an example of endoscopically assisted neurosurgical removal
      of petrous apex meningioma associated with trigeminal neuralgia. Endoscopy was
      used during the operation for control of completeness of tumor removal and for
      identification of offending vessel and control of position of protector. Total
      resection of the tumor was achieved, complete regression of trigeminal pain was
      observed in early postoperative period.

PMID- 22379856
TI  - [Metastasizing of follicular thyroid cancer to the skull base].
AB  - Distant metastases of differentiated thyroid carcinoma are observed in 5-10% of
      cases. Cerebral metastases are common for papillary carcinoma while cranial bones
      are usually affected by metastases of follicular cancer. Diagnostics of
      metastases of follicular carcinoma is complicated due to absence of pathognomonic
      signs and in 42% of cases they represent clinical onset of the disease.
      Neurosurgical treatment of metastases is associated with difficulties caused by
      abundant vasculature and intimate contact with critical structures of the skull
      base. Nevertheless metastases of follicular thyroid carcinoma have relatively
      favorable course: after surgical resection and hormonal replacement therapy and
      local iodine radiotherapy life expectancy is 4.5 years longer.

PMID- 22379857
TI  - [Relationship between changes in peroxide oxidation lipoide index, coenzyme Q10
      and free fatty acids by of rats depending of fatty acid component in the ration].
AB  - Ontogenetic peculiarities of relationship concentration of coenzyme (K0) Q10,
      peroxide oxidation lipoide (POL) content, peroxidation index (PI), concentration
      of omega 3 and omega 6 PUFA and saturated fatty acid in blood serum and liver of
      rats of 1, 3, 9 and 12 months old are studied. In blood serum pronounced riverse
      dependence was discovered between K0Q10 concentration and POL process intensivety
      in rats of 3 to 6 month old, fed palm and linseed oil. Direct relationship was
      established between TBA-active products in liver of all animal groups and
      peroxidation index. Value PI can be used for evaluation of potential substrates
      of POL in experiments and for creation of ration with definite fatty acid
      composition.

PMID- 22379858
TI  - [Toxicological sanitary characterization of silver nanoparticles introduced in
      gastrointestinal tract of rats].
AB  - Water suspensions of silver nanoparticles were introduced intragastrically to
      growing male Wistar rats daily for 28 days. There were studied animals mass gain,
      relative masses of viscera, intestinal barrier resistance against protein
      macromolecules, DNA oxidative damage, tissue non-protein thiol levels, first and
      second phase of xenobiotic detoxication system activity, lysosomal membranes
      stability in liver together with routine blood biochemical and hematological
      indices and caecal's microbiocenose state. The data testifying to possible toxic
      risks, connected with reaction of silver's nanoparticles is obtained.

PMID- 22379859
TI  - [Lipids metabolism at aboriginal adolescents in Russian European North].
AB  - The aim of our research was to investigate the contents of lipids and fat-soluble
      vitamins in blood plasma of aboriginal adolescents of Russian European North
      (komi, n=104). It was established that there are specific Lipemic index at
      aboriginal adolescents: low level of the general cholesterol, triglycerides,
      transport lipoproteins both their albuminous components and raised proportion
      omega-6/omega-3 fatty acids concerning recommended specifications. Level of fat
      soluble vitamins also has been considerably lowered. Adolescents living in 62
      degrees N differed as a completely higher level of atherogenous fractions of
      lipids, than the adolescents of Circumpolar regions (65 degrees N) having
      traditional

PMID- 22379860
TI  - [Food behavior of consumers (for example, Chelyabinsk)].
AB  - Sociological poll of inhabitants of Chelyabinsk concerning a balanced diet was
      conducted. Every second chelyabinets needs change of the food, but thus has for
      this purpose no sufficient money resources. Deficiency in a food of animal
      protein, the majority of vitamins, macro- and microelements and saturation of a
      diet by carbohydrates and fats was shown. It was established that the products of
      mass consumption: bakery, dairy, meat,fat-and-oil products and sweets can be
      considered as potential products for enrichment, oriented for low-and middle
      income countries primarily.

PMID- 22379861
TI  - [The significance of some potentially pathogenic microorganisms in occurrence of
      food toxicosis. Part 1. S. aureus and staphylococcal enterotoxins].
AB  - The data on the nomenclature, classification and properties of staphylococci and
      staphylococcal enterotoxins produced by them are presented. The analysis of
      cultural and biochemical properties of 137 strains of staphylococci isolated from
      raw milk and "Russian" cheese was performed. The high degree of correlation
      between the ability of S. aureus produce enterotoxins and the presence of enzymes
      coagulase, thermostable DNase, and other factors of pathogenicity is established.

PMID- 22379862
TI  - [Influence wheat bran on organism vitamin (experiment on rats)].
AB  - The inclusion of wheat bran (at a dose of 2,3 and 4,6% of the dry weight) in the
      semi-synthetic diet of rats under combined deficiency of vitamins (20 and 50% of
      the adequate level) did not have a significant effect on vitamins C, B1 and B2
      liver levels, riboflavin blood plasma level, and thiamine and riboflavin urinary
      excretion. The consumption of bran in high dose has been accompanied by a
      decrease of retinol blood plasma level on 19-28% but it has no effect on liver
      retinol palmitate content. Bran intake in both doses resulted in a deterioration
      of rats sufficiency with vitamin E, which had been confirmed by a simultaneous
      significant decrease of blood plasma alpha-tocopherol concentration on 31-40%,
      and its liver level on 23-43%. The results obtained indicate the advisability of
      vitamin E enrichment of diets with a high content of dietary fiber.

PMID- 22379863
TI  - [Quality requirements for vitamins in the premix and nutritional supplements].
AB  - A comparison of the functions of vitamins included in the premixes and food
      additives has been carried out. The normative documentation regulating the
      quality parameters, hygienic safety requirements and their usage in the food
      industry has been analyzed.

PMID- 22379864
TI  - [The alimentary status sisk of the hevophilia with the lesion of jointts].
AB  - The diagnostic findings sick of a hemophilia with recurring hemarthrosis are
      presented. At studying of componential structure of a body by a method of
      bioimpedansometriya considerable fluctuations of an index of weight of a body, a
      poor development of a muscular fabric, increase in percentage of a fatty fabric
      that is connected with low, physical activity and increase in the contribution of
      fat in power value of a food ration have been found out in patients. Results of
      research of an actual food by a frequency method with a quantitative estimation
      at sick of hemophilia and healthy students testify to probable risk of
      insufficient consumption of vitamins B1, B2 and calcium, magnesium that demands
      individual correction.

PMID- 22379865
TI  - [Efficacy of complex system of dietary provision of children in critical states.
      Part 2. Developing a system of choice of a method and implementation of
      artificial nutrition of children in critical status].
AB  - To increase efficacy of treatment of children in intensive care departments a
      system of dietary provision of children in critical status has been developed. A
      way of determining the time to start enteral nutrition for such children was
      determined. Study of the effectiveness of mixed (parenteral-enteral) feeding,
      showed its high efficiency as compared with exclusively enteral nutrition, thus
      recommend this method for children with resuscitation and intensive therapy.

PMID- 22379866
TI  - [Soups in human nutrition].
AB  - The article gives information about the soups traditionally used by the
      population of Russia. A classification of soups, their nutrients and energy
      content, as well as the contribution of soups to daily nutrient consumption of
      the population are presented. Taking into account results of epidemiological
      researches of dietary the most popular types of first lunch dishes (soups) in the
      population of Russia were found out.

PMID- 22379867
TI  - [Selenium provision in heart failure of different aetiology].
AB  - Determination of selenium status of patients with chronic heart failure of
      various etiologies showed reduced provision of selenium compared with the control
      group. Statistically significant increased serum levels of selenium have occurred
      on average 35,9% after the correction. Intake of sea cabbage jam led to a
      significant increase in the level of selenium in serum only at patients with
      deficiency of this trace constituent.

PMID- 22379868
TI  - [Determination by high performance chromatography, steroid saponins in a
      biologically active food supplements containing the extract of Tribulus
      terrestris].
AB  - Steroidal saponins are bioactive substances of Tribulus terrestris and can be
      used to assess the quality of raw materials and processed products from them. For
      this purpose has been developed the method of qualitative and quantitative
      determination of steroidal saponins by high performance liquid chromatography
      with spectrophotometric and mass-selective detection and optimal conditions of
      sample preparation (70% methanol extraction with sonication and heating); also
      has been studied steroidal saponins composition of Tribulus terrestris
      (protodioscin, tribulosaponin B, metilprotodiostsin, terrestrozin H,
      prototribestin, gracillin and others were found).

PMID- 22379869
TI  - [New sources of organic form zinc].
AB  - The Comparative analysis of the efficiency of the enzymatic hydrolysis of the
      mussels meat has been carried out, using enzymatic preparations with proteolytic
      action called "Protozim", "Flavoenzyme" and "Pancreatine". Complexes of
      fermentolyzates of the mussels meat with zink have been obtained by the reaction
      of chelating. Prepared fermentolyzates and their complexes with zink have been
      determined by physicochemical methods. Composition of amino acids has been
      determined in fermentolyzates and in their complexes with zink has been
      characterized the content of zink. The valuation of molecular-mass distribution
      of peptide fractions of fermentolyzates and their complexes with zink has been
      given.

PMID- 22379870
TI  - [Food status peculiarities, anthropometric, clinica and biochemical indices at
      professional sportsmen].
AB  - Under steady state conditions in 66 athletes involved in weightlifting,
      bodybuilding, judo and taekwondo have studied features of the metabolic status.
      Data on matter-of-fact nutrition, body weight content within the inter
      competition period, energy exchange, clinical and biochemical indices and
      physical acceptability indices were analyzed. As a result, the decrease indexes
      of metabolism at all the sportsmen and high-level caloric value at sportsmen who
      are engaged in weightlifting, which corresponds their energy expenditures, was
      revealed.

PMID- 22379872
TI  - [Fasting-diet therapy at this stage].

PMID- 22379871
TI  - [L-carnitine in infant formulas].

PMID- 22379873
TI  - [Possible role of serotonin 5-HT2 receptors in mechanism of afobazole anxiolytic
      action: neurochemical study of inter-line differences in mice].
AB  - Effects of separate and combined introduction of afobazole and SB-200646A (highly
      selective 5-HT2B/2C receptor antagonist) on the content of monoamines and their
      metabolites in brain structures of mice of C57/Bl/6 and BALB/C lines have been
      studied using neurochemical methods and high-performance liquid chromatography
      (HPLC). Afobazole (5 mg/kg, i.p.) significantly increased dopamine (DA) level in
      hypothalamus and amygdala of C57/Bl/6 mice, while no changes of DA content were
      observed in BALB/C mice. At the same time, the concentrations of DA metabolites
      dioxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the same structures
      as well as in striatum were decreased compared to control. Afobazole also led to
      a decrease in the content of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT
      index in frontal cortex and amygdala of C57/Bl/6 mice; analogous decrease in the
      latter parameter was observed in striatum of BALB/C mice. The introduction of SB
      200646A (10 mg/kg, i.p.) almost did not influence the neurochemical indices of
      the content and metabolism of monoamines, except for an increase in the HVA
      content in amygdala and the DOPAC and 5-HIAA concentrations in striatum of
      C57/Bl/6 mice. The joint introduction of afobazole and SB-200646A led to an
      increase in the content of norepinephrine (NE) in striatum of BALB/C mice and in
      hippocamp of mice of both lines. The data obtained may be indicative of the
      involvement of NE- and DA-ergic neurotransmitter systems in the mechanisms of
      afobazole action. Enhanced anxiolytic effect of the joint introduction of
      afobazole and SB-200646A can be interpreted as a positive modulation of the
      anxiolytic drug action related to the blocking of 5-HT2-type serortonin
      receptors. The results also reveal inter-line differences of neurochemical
      responses induced by combination of afobazole and selective antagonist of
      serotonin.

PMID- 22379874
TI  - [Neurotropic effects of heptapeptide mystixin studied on brain tissue sections].
AB  - Neurotropic effects of heptapeptide mystixin have been studied on olfactory
      cortex neurons in rat brain tissue sections. The application of mystixin onto
      brain section produced a dose-dependent inhibition of AMPA- and NMDA-receptor
      dependent processes. The peptide suppressed the activity of inhibitory processes
      only at small doses (10, 25, and 50 mg/ml) and potentiated these processes at
      greater doses (100 and 250 mg/ml). These effects of mystixin are reversible:
      after washing, the activities of both exciting (except for NMDA-related) and
      inhibitory mechanisms were restored.

PMID- 22379875
TI  - [Efficacy of emoxipine and mexidol in patients with chronic disorders of the
      digestive system and atherosclerosis of the abdominal aorta].
AB  - The influence of emoxipine (2-ethyl-6-methyl-3-hydroxypyridine hydrochloride) and
      mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) on the content of lipid
      peroxidation products in peripheral blood and the dynamics of clinical symptoms
      of gastrointestinal tract pathology has been studied in patients of middle and
      senile age with atherosclerosis in the abdominal aorta. It is established that a
      two-week 3-hydroxypyridine derivatives leads to a decrease in the level of lipid
      peroxidation products. The administration of emoxipine led to the most pronounced
      control of pain.

PMID- 22379876
TI  - [Neuroprotector therapy of patients with decompensated diabetes mellitus type 1].
AB  - The influence of actovegin and reamberin on diabetic ketoacidotic crises has been
      studied on a group of 128 patients with severe diabetic ketoacidosis on the
      background of diabetes mellitus type 1 with disorders ranging from consciousness
      to coma or precoma states. Patients of group 1 received standard intensive
      therapy of diabetic ketoacidosis. In group 2, an intensive therapy for
      neuroprotection by actovegin was added. In group 3, patients received reamberin
      on the background of standard therapy. In group 4, the neuroprotective therapy
      using actovegin and reamberin was combined. The mental status was estimated upon
      recovery from coma, on 5th and 28th days from the beginning of treatment, by
      taking into consideration cognitive functions such as attention, memory,
      mentality. The results showed that the use of neuroprotective drugs, including
      the combination of actovegin and reamberin, allowed to the restore the
      compensatory-adaptive reaction of patients to ketoacidotic crisis, accelerate the
      restoration of consciousness within 19.2 +/- 3.8 h, restore the cognitive
      functions with exceeding norm for patients with diabetes mellitus in compensation
      stage and maintain their high level on 28th day after crisis.

PMID- 22379877
TI  - [Anti-inflammatory effects of amitriptyline, diazepam and mebicar using model of
      acute carrageenan-induced paw edema in rats].
AB  - The anti-inflammatory activity of amitriptyline, diazepam and a new, Russian
      tranquilizer mebicar was studied in a wide range of therapeutic doses on
      carrageenan-induced paw edema in rats. Mebicar at low doses showed greater and
      longer (up to 24 h) lasting anti-inflammatory activity as compared to that of
      amitriptyline and diazepam.

PMID- 22379878
TI  - [Influence of perftoran on pharmacokinetics of hydrophilic drugs].
AB  - Influence of perfluorocarbon blood substitute Perftoran on pharmacokinetics of
      cefazolin (20 mg/kg), cefotaxime (25 mg/kg), ciprofloxacin (4 mg/kg) and
      pentoxifylline (10 mg/kg) upon their intravenous introduction separately or
      immediately after Perftoran infusion (5 ml/kg) was investigated on rabbits. It
      was found that the presence of Perftoran accelerated the transfer from blood to
      tissues for Cefazolin and Cefotaxime, which have negative values of the
      distribution logarithm in octanol/water (logP = -0.4 and -1.4, respectively).
      With respect to pentoxifylline and ciprofloxacin, which are less hydrophilic, the
      effect of pharmacokinetic interference was either weaker or absent. Probably, the
      infusion of hydrophobic Perftoran nanoemulsion enhances the hydrophobicity of
      blood plasma, which is a prerequisite for the more intensive transfer of
      hydrophilic ligands from blood to tissues.

PMID- 22379879
TI  - [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their
      nootropic action in alloxan diabetes].
AB  - Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic
      acid derivatives (emoxipine, reamberin and mexidol) and their effect on
      conditional learning, glycemia, and lipidemia was studied in rats with alloxan
      induced diabetes. In parallel, the analogous relationship was investigated for
      alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic
      neuropathy. It was established that single administration of emoxipine and
      mexidol in mice in doses equivalent to therapeutic-range doses in humans produces
      antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in
      test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree
      of antihypoxic action. Reamberin does not exhibit this effect. The introduction
      of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan
      diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in
      humans corrects conditional learning disorders in direct relationship with the
      antihypoxic activity of these drugs. The development of the nootropic effect of
      emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in
      hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic
      action of reamberin is accompanied by a transient hypoglycemizing effect and
      aggravation of dyslipidemic disorders. The antihypoxic activity of investigated
      drugs determines the direction and expression of their lipidemic effect, but is
      not correlated with the hypoglycemizing action these drugs on test animals with
      alloxan diabetes.

PMID- 22379880
TI  - [Characteristics of immune response to etiotropic and pathogenetic therapy in
      children with chronic hepatitis C].
AB  - Features of the immune response of children with chronic hepatitis C to the
      antiviral and pathogenetic therapy have been studied. It is shown that the
      antiviral therapy is accompanied by stimulation of the immune response as
      manifested by the synthesis of cytokines (IL-4, IFN-alpha, IFN-gamma) with
      retention of increased production of IFN-a for more than two years after the end
      of the course of treatment. In children that previously received interferon
      inductor (cycloferon) for 12 months, high level of IFN-a production is retained,
      which ensures antiviral protection. Phytotherapy did not influence the production
      of cytokines.

PMID- 22379881
TI  - [Methodological approaches to studying substances influencing blood rheology].
AB  - Optimum design of preclinical research for pharmacological agents influencing the
      rheological properties of blood is presented. Models of hyperviscosity syndrome
      and approaches to studying the hemorheological activity mechanisms are described.

PMID- 22379882
TI  - [Treatment of advanced ovarian cancer: results of the Department of Clinical
      Pharmacology and Chemotherapy, N.N. Blokhin RORC from 1993-2010].
AB  - The aim of this study was to analyse the outcome of ovarian cancer depending on
      the type of surgical debulking, the strategy of treatment of recurrent cancer,
      and other clinical factors. We performed retrospective analysis of patients with
      stage IC-IV ovarian cancer treated at the Department of Clinical Pharmacology and
      Chemotherapy in 1993-2010. A total of 353 patients were included. The medians of
      progression-free and overall survival were 11.3 and 40.8 months respectively. The
      results of the treatment depended on the mode of surgical debulking, histological
      type and stage of the tumour, regimen of front-line chemotherapy. The main
      prognostic factor in recurrent ovarian cancer was the number of potentially
      effective anticancer agents used during the treatment.

PMID- 22379883
TI  - [Lymphodissection in the treatment of early stomach cancer: D1 or D2?].
AB  - The study was designed to analyse results of D1- and D2-lymphodissection in 394
      patients with early stomach cancer between 1990-2007. Risk factors of lymphogenic
      metastasis (lymphatic invasion, submucous invasion, tumour size in excess of 4
      cm, venous invasion, tumour spread to the oesophagus, type 0I and 0II tumors,
      poor differentiation) are considered to be an absolute indication for D2
      lymphodissection that allows to significantly reduce the frequency of relapses
      and improve the outcome of surgery. The restriction of surgery volume to D1
      lymphodissection is possible only in patients with negligibly low risk of
      metastasis regardless of the type of early cancer.

PMID- 22379884
TI  - [New minimally invasive methods for internal bile outflow in oncology].
AB  - A few novel minimally invasive techniques are described for catheter-free repair
      of internal bile outflow in patients with neoplasms in the biliopancreatoduodenal
      region complicated by mechanical jaundice and in cases of iatrogenic
      complications of surgical treatment. The methods based on a combination of modern
      interventional radiologic and endoscopic technologies allow to improve the
      outcome of antineoplastic treatment and the quality of life in certain categories
      of patients. The introduction of these techniques into clinical practice of
      specialized medical facilities may help to optimize the treatment strategy,
      reduce the volume of surgery whenever it can be confined to minimally invasive
      treatment, decrease the employment index, increase the surgical bed turnover rate
      and other economic characteristics of a surgical clinic.

PMID- 22379885
TI  - [Phenotype of immunocompetent cells and its role in antitumour immune response].
AB  - The paper contains an overview of the role of certain minor subpopulations of
      lymphocytes in tumour growth and of the main results obtained in the studies of
      the phenotype of immunocompetent cells from cancer patients. Special attention is
      given to selected indicators of immunity as predictors of the disease and
      efficacy of immunotherapy.

PMID- 22379886
TI  - [Interdisciplinry approach to the treatment of diffuse germinogenic ovarian
      tumours].
AB  - The first stage in the treatment of disseminated germinogenic ovarian tumours
      (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group.
      Dynamic observation is indicated in case of incomplete induction in patients with
      seminoma excepting those with PET-positive residual tumours bigger than 3 cm to
      whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated.
      Ablation of residual tumour of any localization is indicated to patients with
      disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of
      tumour markers. The necessity of adjuvant chemotherapy in case of a viable
      malignant HOT in the removed tissues remains debatable. Refractory and recurring
      HOT are usually treated with a combination of fosfamide and vinblastine. Residual
      tumours need to be removed after salvation chemotherapy. Surgical treatment is
      the preferred option for the management of late NHOT relapses.

PMID- 22379887
TI  - [Advances in radiotherapy of malignant tumours].
AB  - The authors discuss changes in the equipment and technologies of radiotherapy
      during the past 10-15 years. These changes ensured the improvement of diagnostics
      and treatment of neoplasms by two other main methods, surgical and medicamental.
      Modifications in the combined application of radiotherapy and surgery and of
      radio- and pharmacotherapy are discussed.

PMID- 22379888
TI  - [Efficacious anesthesiological and resuscitation care--the cornerstone of modern
      oncosurgery].
AB  - A few modern concepts of anesthesiological and resuscitation care during
      complicated surgical interventions are considered with special reference to
      multimodal anesthesia as a principal tool for the protection of the patient from
      a surgical trauma based on the rational combination of three-component epidural
      analgesia (ropivacaine, fentanyl, and adrenalin) with sevoflurane inhalation
      narcosis and extention of the same epidural analgesia to the early postoperative
      period. The basic principles of infusion-transfusion therapy for the treatment of
      massive intraoperative blood loss ensuring its tolerability by the patient are
      discussed. Special attention is given to the problem of hospital-acquired
      infections and sepsis in oncosurgery. Methods are proposed for the improvement of
      the management of septic shock including immunomodulation, respiratory support,
      infusion and anti-infective therapies. It is concluded that the use of these
      conceptual approaches permits to perform extensive surgical interventions in
      patients with the initially low reserve capacity of vital functions.

PMID- 22379889
TI  - [Li-Fraumeni syndrome: clinico-molecular diagnostics and medico-genetic
      counseling].
AB  - Li-Fraumeni syndrome (sarcoma family syndrome, OMIM 151623) is a rare clinically
      and genetically hetergoeneous autosomal dominant disorder characterized by the
      evolvement and accumulation of soft-tissue osteogenic sarcomas in members of a
      family, as well as uni- and bilateral breast cancer in young women, brain
      tumours, adrenocortical cancer, and lymphoproliferative diseases. Germinal
      mutations of the TP53 gene constitute the etiological genetic basis of Li
      Fraumeni syndrome. American Society of Clinical Oncology (ASCO) and National
      Comprehensive Cancer Network developed recommendations for genetic testing and
      observation of carriers of TP53 mutations. In vitro and in vivo studies
      demonstrated correlation between the TP53-mutant genotype and resistance to
      standard therapeutic modalities. This finding gave impetus to the development of
      new genotherapeutic approaches to the treatment of TP53-associated tumours in
      patients with Li-Fraumeni syndrome.

PMID- 22379890
TI  - [Collagen fiber pathology in atherosclerotic plaques of the coronary arteries in
      ischemic heart disease].
AB  - Structure-metabolic changes of collagen fibers (CF) in atherosclerosis plaques of
      the coronary arteries in the conditions of ischemic heart disease (IHD) have been
      studied. Segments of the coronary arteries were received from 68 men after a
      coronary artery bypass grafting. CF was study with using of the Van Gieson's and
      the Masson's methods. Histologic slices were studied by polarization microscopy.
      The atherosclerosis plaques with IHD were notable for lipidosis of CF. We've
      suspected lipidosis of CF is a crucial factor for the development of
      atherosclerosis plaques instability. Evident lipidosis of CF was attended with
      destructive changes probably resulted in accumulation of atheromatous mass in
      atherosclerosis plaques.

PMID- 22379891
TI  - [Morphometrical characteristic of atherosclerotic plaques in the coronary
      arteries of humans with ischemic heart disease according to their instability
      index].
AB  - Morphometrical research of the atherosclerosis plaques (AP) instability and
      responsible for decreasing of their stability structure has been carried out by
      estimation of the instability index (II). II is a ratio between sum of
      destabilizing (lipids and macrophages) and stabilizing (collagen fibers and
      smooth muscular cells) AP structures. Segments of the coronary arteries were
      received from 45-65 years old man after a coronary artery bypass grafting.
      Histologic, histochemical and computer morphometric methods were used. II for
      every AP was estimated according to the formula introduced by M. Shiomi [22]. 3
      types of AP instability degree were distinguished: stable (II < 1 for AP and AP's
      cover), conditionally stable (II > 1 for AP and II < 1 for AP's cover) and
      unstable (II > 1 for AP and AP's cover). Unstable APs were subdivided into
      potentially dangerous with disruption risk and really dangerous with integrity
      disorders (tears, disruptions, erosion, and necrosis). The potentially and really
      dangerous instability AP was more than in 50% of researched AP. Instability
      degree of AP depended on quantity of stabilizing structures, especially collagen
      fibers.

PMID- 22379892
TI  - [Myocardial morphological changes in atrial fibrillation].
AB  - Hearts of 21 died patients with ischemic heart disease (IHD) have been studied by
      histlological and morphometrical methods. The atrial auricles derived after
      operation of 66 patients with heart diseases and IHD have been researched by
      automatic semiquantitative and immunohistochemical techniques. In general atrial
      fibrillation (AF) has been evident in chronic myocarditis probably conditioned by
      viral infections. In quantity of observations enterovirus and parvovirus B19
      antigens have been found out in myocardium. In 18% studied myocardium antigen of
      adenovirus has been established. The result of myocarditis has been fibrosis and
      adiposis. In myocardium of patients with AF diffuse amyloidosis has been
      abundant. Amyloid depots have been established in perimuscular stroma, under
      endocardium, in vascular walls and cardiac hystiocyte. The group of patients with
      paroxysmal AF has differed from the group of stable AF by fibrosis degree.

PMID- 22379893
TI  - [About development of chlamydia multiple organ lesions after primary ocular
      infection in experiment].
AB  - Chlamidia spp. are obligate intracellular pathogens that cause a variety of
      diseases in humans and animals. Their generalization was proved as hematogenic
      spreading from the urogenital (C. trachomatis) and the respiratory (C.
      pneumoniae) systems. The goal was to investigate the possibility of C.
      trachomatis infection spreading from the primary ocular gate. 6 animals were
      infected by instillation in the conjunctival sack, subconjunctival and
      intravitreal injections of C. thachomatis culture. C. trachomatis was detected by
      direct immunofluorescence method in the retina, retinal pigment epithelium,
      choroid, brain, the pancreas, the prostate gland and the urethra after primary
      ocular infection. The results of our study have proved the opportunity of C.
      trachomatis to cause polyorganic contamination.

PMID- 22379894
TI  - [Keratin 8 expression in mouth mucosa hyperkeratosis and squamous cell carcinoma
      ].
AB  - The immunohistochemical study of proliferation and intermediate filament--keratin
      8 expressions at oral hyperkeratosis and oral Squamous cell carcinoma (OSCC) has
      been carried out. It has been shown, that the specific character of keratin 8
      expressions can be used in differential diagnosis between oral hyperkeratosis and
      OSCC. Different types of oral hyperkeratosis (without atypia, SIN1, SIN2 and
      SIN3) can be differentiated by Ki-67 and keratin 8. We have found the moderate
      positive correlation between proliferation and a keratin 8 expression in
      neoplastic epithelial cells.

PMID- 22379895
TI  - [Pathogenic aspects of influenza during the epidemics caused by A/H1N1v virus in
      2009-2010 according autopsy data].
AB  - The paper is based upon the results of clinic-pathological and virological
      correlations in 29 lethal cases of influenza in Saint-Petersburg and Leningrad
      region during the epidemics 2009/2010. Immunohistochemical analysis of lungs,
      heart and brain using monoclonal sera to HA and HP proteins of influenza virus,
      virological and morphological analysis of experimental influenza in mice infected
      by A/WSN/33 (HIN1) and A/California/07/09 (H1N1) viruses had been carried out. In
      the majority of investigated strains was proved the amino acid mutation with
      replacement D222G. The replication of virus was demonstrated at the late stages
      of diseases, but the desquamation of respiratory epithelium and cytoproliferative
      weren't found out. Besides the "influenza cells", previously described by A. V
      Zinserling the cells with enlarge light nuclei were observed. Patients with
      influenza died from respiratory distress syndrome with minimal bacterial
      infection. We've established that H1N1 virus not only damages the cells of
      respiratory epithelium and alveolar macrophages but it can injure endothelium of
      different organs and neuroglia. The questions which have to be discussed are
      listed.

PMID- 22379896
TI  - [Cryptogenic and iatrogenic papillary thyroid carcinoma in children and
      adolescences: comparative study].
AB  - The clinico-morphological investigations of 117 children and adolescences with
      papillary thyroid carcinoma, surgically treated in the Republic Centre for
      Thyroid Tumors, Minsk, Belarus in 1995-2009 and dutifully followed-up have been
      studied. Ninety -five observations of all cases were sporadic, but 22 patients
      had been treated earlier from other neoplasm (Hodgkin's diseases, malignant
      lymphoma, leukemia, sarcoma, medulloblastoma). Epidemiologic, clinical and
      pathological peculiarities of thyroid carcinoma in Belarus were analyzed. A
      number of features distinguished "cryptogenic" and "iatrogenic" papillary thyroid
      carcinoma in children and adolescents were found out.

PMID- 22379897
TI  - [Intestinal malrotation: genetics features and other congenital malformations in
      children].
AB  - The article is devoted to features of prenatal development of children with
      intestinal malrotation. Mass, height, head and chest circumferences of children
      after birth have been studied. In addition all associated malformations, a blood
      group (ABO system) and the rhesus-factor have been investigated. In comparison to
      the control group of newborn the disorders of prenatal development have included
      associated malformations, low anthropometric data after birth, decreasing of pA
      gene frequency. Notable, children with intestinal malrotation have had high
      frequency of malformations as in the abdominal and thoracic cavities as outside
      intestinal innervations: the small pelvis, the facial skeleton, the upper and
      lower extremity.

PMID- 22379898
TI  - [The role of cervical transformational zone as an object of human papilloma virus
      oncogenic effect in cervical intraepithelial neoplasms and invasive cancer
      development].
AB  - The correlation of morphological mistakes in neoplasia grade verification from
      visibility of transformation zone (TZ) and patient age was studied in 503
      patients with CIN and microinvasive cervical cancer. The square of ectocervix
      lesion was defined by LeiseCap software in colposcopic working station Leisegang
      3MV. The exclusive significance of TZ in HPV-associated cancerogenesis was
      confirmed clinically. We've established that the neoplasia stage increases with
      age while lesion extension and TZ visibility decrease dramatically leading to the
      subsequent decrease in colposcopy sensitivity and adequacy of guided biopsy. The
      critical age for underdiagnosis of latent lesions seems to be 35 years. The
      diagnostic and therapeutic value of conization and the large loop excision of the
      TZ (LLETZ) as the procedures with the optimal TZ excision in patients with
      visibly unchanged ectocervix are confirmed in cases when CIN 2-3 and
      microinvasive cancer are suspected.

PMID- 22379899
TI  - [Morphological characteristics and prognostic criteria for gastrointestinal
      stromal tumors].
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms
      of the gastrointestinal tract. Analysis of GIST morphology is necessary for
      selection of primary patients with the high risk of tumor progression for
      adjuvant treatment with gleevek following complete gross resection of KIT (CD
      117)-positive GIST. In this study we've analyzed morphological parameters and
      survival of 120 GIST patients before target therapy. According to risk
      stratification of primary GIST by tumor location, size and mitotic index (mitoses
      per 50 visual fields) 44% of gastric GISTs, 87,5% of small bowel GISTs and 100%
      of rectum GISTs have been classified as high risk group. There was no significant
      difference between survival of patients with different type of GIST, Ki-67
      proliferative index and presence of necrosis.

PMID- 22379901
TI  - [Congenital galactosemia in newborn infant with vascular malformation of the
      internal organs].
AB  - The paper describes a case of hereditary thesaurismosis - galactosemia in neonate
      infant with mutation of GALT-gene (Q188R/N) and vascular malformation of the
      internal organs.

PMID- 22379900
TI  - [The rare case of laryngeal lesion in idiopathic Kaposi's sarcoma].
AB  - The case report of laryngeal Kaposi's sarcoma (KS) in 59 year old HIV-negative
      man infected by herpes virus 8 (HHV-8) is in the paper. The primary onset of KS
      was on the legs. Lesion of laryngeal mucosa was developed sequentially, resulted
      in laryngeal stenosis and led to application of tracheostome. The skin and
      laryngeal mucosa lesions had homotypic histological structure and corresponded to
      early manifestation of KS preceded tumor node appearance.

PMID- 22379902
TI  - [Prognostic factors of renal cell carcinoma].
AB  - The crucial predictor of renal cell carcinoma (RCC) is a clinical stage, although
      the significance of this parameter isn 't confirmed for all histological types of
      carcinomas. It remains unknown what factors ensure the sensitivity of the tumor
      to chemotherapy and why metastasis is accompanied by the development of
      resistance to therapy. The data about the prognosis of RCC rare variants are
      extremely scarce. Ubiquitin-dependent proteolysis plays an important role in the
      development of RCC, but the prognostic significance of this signal way's proteins
      is poorly understood. In order to find out significant factors for prognosis of
      RCC clinical course it's necessary to use the complex spectrum of tumor growth
      regulation factors and genetic tests.

PMID- 22379903
TI  - [Glandular lesions of the cervix].
AB  - In the review the most abundant types of cervical glandular lesions including
      precancerous lesions and benign hyperplastic, metaplastic and ectopic changes are
      considered. The most popular classifications, their advantages and disadvantages,
      morphological criteria, and the principles of differential diagnosis are
      discussed. The basic areas of an immunohistochemical study and the specific
      features of different markers expression used for differential diagnosis are
      covered.

PMID- 22379904
TI  - [Metabolic disorders as a result of intestine ischemia and it's defensive factors
      due to aorta prosthetics and cross-clamping of descending aorta before celiac
      trunk].
AB  - The perfusion of internal organs is affected during cardiac surgery of descending
      aorta and cross-clamping before (upper) celiac trunk as well as extracorporeal
      circulation. The aim of study is to investigated methods of decreasing negative
      effects on intestine perfusion which leads to metabolic disorder. Two groups were
      studied: 11 patient with epidural anesthesia and 11 patient with pulmonary atrium
      femoral bypass. For mesenterial perfusion monitoring was used intraluminal
      tonometry. 11 patient of control group had significant changes in level of
      lactate and glucose as well as data of intraluminal tonometry which is evidence
      of mesenterial ischemia. Same changes were discovered in the group of patient
      with epidural anesthesia. However group with pulmonary atrium - femoral bypass
      had minimal metabolic abnormalities similarly to data of tonometry. Above all
      administrating epidural anesthesia had positive effect in early post operative
      period and restore intestine motility.

PMID- 22379905
TI  - [Combined inhalation and epidural anesthesia, during aortocoronary bypass surgery
      on beating heart].
AB  - Aim of study is to compare efficiency and safety of different methods of combined
      inhalational and epidural anesthesia during aortocoronary bypass surgery on
      beating heart. SUBJECTS AND METHODS: 40 patients suffering from coronary heart
      disease were included in randomized study. Two methods of combined inhalational
      and epidural anesthesia were compared. The first group of 22 patients were
      administrated extended-release epidural anesthesia with Ropivacaine 0.3% in upper
      thoracic region and Sevoflurane as a volatile agent. Second group of 18 patients
      were administrated Isoflurane and epidural anesthesia. Monitoring: (Harvard
      standard of monitoring), BIS, invasive monitoring of hemodynamic, the dose of
      anesthetic gas, internal medical audit. Result of the study showed that all
      patient had same duration of surgery, level of unconsciousness (BIS 40-45%) dose
      of valiant anesthetic agents less than 1 MAC, same dose of Ropivacaine, minimal
      dose of opioids, quantity and quality of intravenous infusion therapy and same
      amount of vasopressors. It was discovered that Sevoflurane had influenced
      hemodynamic less than Isoflurane. The results of internal retrospective medical
      study showed safety of both methods of anesthesia. Sevoflurane allowed fast
      postoperative recovery on 1,74 times ,early extubation in theater on 1,64 times.
      Both methods of combined anesthesia epidural and inhalational presented good
      results and can be performed in coronary bypass surgery but for fast-track
      surgery and anesthesia use of Sevoflurane is better.

PMID- 22379906
TI  - [Cardioprotective properties of sevoflurane in coronary bypass surgery with
      extracorporeal circulation].
AB  - The aim of the study is to investigate cardioprotective properties of sevoflurne
      during coronary bypass surgery with extracorporeal circulation. METHODS: 60
      patients with coronary heart disease (left ventricular ejection fraction
      61,3+1,0%) underwent surgery with extracorporeal circulation. Inhalation
      anesthesia with Sevoflurane and TIVA were performed. Hemodynamic, troponin level,
      KFK, protein of heart shock in plasma (PHS 70) and PHS in myocard were monitored.
      RESULTS: patients who were administrated with Sevoflurane had lower level of
      troponin than patients of second group. In postperfusion period the amount of PHS
      70 in myocard increased in 1.6 times than in preperfusion period in comparison to
      TIVA method this figure did not change. There was negative correlation in level
      of PHS 70 in plasma and troponin in first day after the operation (r = -0,61 p <
      0,05) and second day (r = - 0,76, p < 0,05). In conclusion Sevoflurane had
      affected hemodynamic less than TIVA. Increased level of PHS has cardioprotective
      effects.

PMID- 22379907
TI  - [Role of endogenous intoxication in multiple organ dysfunction development in
      cardiosurgical patients in early postoperative period].
AB  - PURPOSE: to evaluate endogenous intoxication (EI) and multiple organ dysfunction
      (MOD) in cardiosurgical patients after open heart surgery. PATIENTS AND METHODS:
      twenty six patients with MOD signs and 29 patients with an uneventful
      postoperative period were studied. MOD severity was assessed with SOFA scoring.
      EI was quantified with middle molecular weight peptides (MMWP), malondialdehyde
      and couple triens. RESULTS: on the first postoperative day MOD patients were
      characterized by high EI (MMWP: +36.7%), while control patients had a mild EI
      (MMWP: +20.7%). On the 3rd-4th postoperative days in the main group SOFA scores
      was decreased and EI intensity was increased (MMWP: +43.3%), while in the control
      group EI fitted the preoperative value. The major defference on the 10th-12th
      postoperative day was observed. In the main group severity of MOD matched that
      over the previous period. The intensity of EI remained elevated (MMWP: +30%),
      while in the control group EI level was equal to the baseline. The correlation
      analysis showed a positive relationship between EI and MOD pareameters, and
      positive connection between EI/MOD parameters and cardiopulmonary bypass/aortal
      occlusion duration. CONCLUSION: patients with MOD have more considerable EI
      compared with an uneventful postoperative period. EI increase is one of the main
      causes of MOD development in cardiac surgery patients. Cardiopulmonary
      bypass/aortal occlusion potentiate endogenous intoxication and MOD development
      after cardiac surgery.

PMID- 22379908
TI  - [General anesthesia vs combined anesthesia during internal carotid artery
      surgery].
AB  - Methods 50 patients underwent surgery on internal carotid artery. The first group
      of patients were performed combined anesthesia with Propofol , Phentanil and
      superficial cervical plexus block (SCPB). Second group were administrated
      Phentanil and Propofol. Monitoring: blood pressure, BIS, dose of anesthetic
      agents. Results of study indicated that combined method of anesthesia with SCPB
      provided better brain perfusion because of high level of MBP (mean blood
      pressure) at the time of occlusion of ICA and more stable hemodynamic indices. In
      addition second group of patient had longer period of recovery due to higher dose
      of Phentanil than the first group. CONCLUSION: Combined anesthesia with propofol,
      phentanil and CPB provides better analgesia and require less dose of opiodes
      anesthetics.

PMID- 22379910
TI  - [Effective epidural anesthesia for cesarean section in parturient woman with type
      I mucopolysaccharidosis (Hurler's syndrome)].
AB  - Mucopolysaccharidosis is genetically determined disease caused by the deficiency
      of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown
      pathway. This metabolic block leads to the accumulation of GAG in various organs
      and tissues and affects nerve system, eyes, internal organs and musculoskeletal
      system. The reviewer of various articles on pubmed showed only one article about
      epidural anesthesia in patient with type I mucopolysaccharidosis. Our observation
      allows to consider that epidural anesthesia with ropivacaine is possible and safe
      in patients with type I mucopolysaccharidosis.

PMID- 22379909
TI  - [Spinal anesthesia with various anesthetic agents due to endoscopic urological
      procedure in patient over 60 years old].
AB  - Aim of the study is to compare efficiency and safety of method of spinal
      anesthesia with isobaric bypivacain (5 mg/ml) and ropivacain 5 (mg/ml) during
      performing transurethral resection of the prostate in patients over 60 years old.
      Methods 38 patients (68-82 years old ASAII-ASAIII) with hyperplasia of prostate
      gland were examined in randomized clinical study. Two methods of anesthetic
      management were compared. In first group of 19 patients was administrated
      intrathecal with isobaric bypivacain (5mg/ml), second group of 19 patients were
      administrated with ropivacain (5mg/ml). The efficiency of spinal anesthesia was
      estimated. Monitoring: Harvard standard of monitoring, ectodermic activity,
      characteristic of heart rhythm, medical audit. All patients in both groups were
      same age, physical status, anthropometric information, had equal duration of
      surgery and dose of local anesthetic agent (15mg). However difference between
      efficiency of spinal anesthesia was discovered. In group with bypivacain sensory
      block developed in 1.35 times faster it lasted on 1.22 time longer and motor
      block developed in 1.4 times faster with a longer duration in 1.32 times than
      group with ropivacain. Hemodynamic and condition of vegetatic homeostasis in both
      groups were almost equal but analyzed data presented that ropivacain (5 mg/ml)
      influenced hemodynamic less. Results of retrospective study demonstrates that it
      is safer to use isobaric ropivacain (5 ml/mg) in elderly patients for spinal
      anesthesia in 1.5 times p = 0,007). In conclusion spinal anesthesia with isobaric
      bypivacain (5mg/ml) more efficient because of duration and time of development of
      neuroaxial block on the other hand isobaric ropivacain 5 mg/ml is safer to use in
      patients older than 60 years old.

PMID- 22379911
TI  - [Comparison of various techniques of spinal anesthesia in day surgery].
AB  - Clinical effects of various techniques of spinal anesthesia in day surgery were
      studied. Duration of anesthesia, time of block beginning, the spread of sensor
      and motor block was assessed. The episodes of hypotension were associated with
      one side spinal anesthesia. In a group with Suddle block the blood pressure was
      normal as well as hemodynamic those patients had no need of intravenous fluid
      therapy or other drugs.

PMID- 22379912
TI  - [Role of regional anesthesia in prevention of postoperative respiratory
      dysfunction].
AB  - The aim of the study is to evaluate postoperative respiratory dysfunction in
      abdominal surgery based on level of invention and type anesthesia and
      postoperative pain management. SUBJECTS AND METHODS: 260 patients who underwent
      major abdominal surgery were assessed. 70 had operation in upper abdomen and were
      administered general anesthesia, 70 patients had same operation but had combined
      anesthesia inhalational and prolonged epidural on thoracic level. 120 patients
      were performed abdominal operation in lower abdomen 40 of them were administered
      with general anesthesia 40 patient had combined anesthesia inhalational with
      prolonged epidural and 40 had combined anesthesia inhalational and spinal
      anesthesia. We analyzed anesthesia and recovery period, postoperative pain
      management and sedation, the result of spirometria and arterial blood gasses.
      RESULT: both methods of regional anesthesia allowed to reduce amount of
      anesthetic agents and due to this shortened the time of anesthetic recovery. The
      results of spirometria were affected in all groups particularly in a group with
      abdominal surgery on upper region. Epidural anesthesia provided best result in
      postoperative pain management and improved result of spirometria in patients
      after abdominal surgery in upper and lower region. In addition patients after
      upper and lower abdominal surgery how received epidural analgesia in
      postoperative period had demonstrate better arterial blood gasses results than
      patients of all other groups. Method of spinal anesthesia did not demonstrate
      beneficial effects on the results of spirometria or arterial blood gasses. The
      rate of postoperative pneumonia was lower in groups with regional anesthesia.
      CONCLUSION: extended-release epidural anesthesia was beneficial effects on
      postoperative respiratory dysfunction and reduces rate of pneumonia
      postoperatively.

PMID- 22379914
TI  - [Post amputation phantom pain syndrome medical and social problems].

PMID- 22379913
TI  - [Comparison of analgesics using two devices for the patient-controlled
      analgesia].
AB  - The patient-controlled analgesia with two devices allows to compare analgesic
      agent and to regulate quantity and quality of multimodal analgesia compounds. The
      aim of the study is to compare efficiency of analgesic agents in method of
      patient controlled analgesia with two devices. SUBJECT AND METHODS: 38 patients
      after major abdominal surgery were included in the prospective blind randomized
      study the first group of patient conducted with two PCA devices one apparatus was
      with morphine other one with placebo. Second group of pations were administered
      morphine and lornoxicam. The doses of analgetic agets were equal in all devices.
      The level of pain was measured according to visual analog scale (VAS) patients
      were asked to determine which analgesic providing best result also side effects
      of analgesia were registered. RESULTS: There were no differences in the intensity
      of pain between the groups. The latter did not differ in the number of adverse
      reactions. The largest number of patients of first group made their chose towards
      morphine 63%; 25% prefer placebo p < -0,05; 12% could not make their choose.
      CONCLUSION: Most of patients who received morphine and placebo can determine the
      analgesic agent. Second group of patients choose both analgesic agent equally
      often. Comparative assessment of analgesics, by employing 2 PCA apparatuses in
      one patient, allows evaluate the efficiency of analgesics added to the
      conventional methods.

PMID- 22379915
TI  - [Analysis of patients control analgesia with trimeperidine and ketoprofen for
      postoperative pain management in patients who underwent cardiac surgery].
AB  - The aim of the study is to discover adequate method of early postoperative period
      pain management in patients after cardiac surgery. In prospective randomized
      competitive study were analyzed three algorithms of analgesia: first patients
      controlled analgesia (PCA) with trimeperidine and (NSAID) ketoprofen, second PCA
      with only trimeperidine and third is ketoprofen combined with intramuscular
      injection of trimeperidine. There were 75 pations studied at the age of 40 to 65.
      The pain level was assessed according to verbal 5 points scale, inspiration lung
      capacity which was measured by incentive spirometry. It was shown that NSAID were
      safe to use in early postoperative period in patients after cardiac surgery.
      Combination of ketoprofen and trimeperiden showed best results in pain
      management. Consumption dose of trimeperidine was smaller in first group but
      larger than in third group where this drug was introduced fractional. All side
      effects were associated with trimeperedine and were depended on a dose. Patients
      of second group had nausea, vomiting, dizziness, weakness, enteroparesis
      considerably often comparing to patients of other groups, moreover rate of
      enteroparesis was minimal in the third group.

PMID- 22379916
TI  - [Chronic non-malignant pain definition and stages of therapy].
AB  - The treatment of chronic non-malignant pain is actual medical problem. Varies
      clinical symptoms and absents of treatment standards make those problems very
      difficult to manage. We presented basic concept of chronic pain and
      multidisciplinary stages of treatment.

PMID- 22379917
TI  - [Combined invasive methods of treatment of patients with chronic pain syndrome].
AB  - 1505 patients with combined chronic pain syndrome were treated. All of them
      suffered from different orthopedic pathology. Lack of examination and mistakes of
      previous treatment lead us for this investigation. Using different kind of blocks
      in treating patients at the visit was a treatment method and decrease level of
      pain significantly during the first days, increase quality of life and motivation
      to recovery.

PMID- 22379918
TI  - [Intravenous and transfusion therapy and acid-base balance during liver
      transplantation].
AB  - The aim of the study is to investigate the influence of intravenous fluid therapy
      and transfusion therapy with different amount of fresh frozen plasma and
      crystalloids. SUBJECT AND METHODS: 66 patients underwent cognate liver
      transplantation were divided into three groups. First received fresh frozen
      plasma and crystalloids at the ratio of 1:2 Second group FFP and crystalloids at
      the ratio of 1:1. Third at the ratio of 2:1 FFP and crystalloids. pH, SBC, PCO2,
      lactate was measured at the period of cross-clamping vena cava (anhepatic phase)
      and at the end of the surgery. As well as anion difference (AD), excess and
      deficiency of anion difference HCO3 = [(AD-12/24-HCO3)] or difference difference.
      RESULTS: First group of patient who received FFP 5423+ 417 ml. and crystalloids
      11048+ 458 ml. demonstrated metabolic acidosis pH 7,309+0,02 and 7,323+0,01; SBC
      17,72+0,96 and 18,36+1,76 mmoll/l; lactate 3,0+1,08 and 2,33+1,16 mmoll/l;
      difference difference 0,47+0,13 and 0,51 +0,25; chlorine 114,65+1,5 and
      114,25+0,7 mmoll/l. At the end of anhepatic phase and at end of the operation the
      acidosis formed because of increased level of lactate as well as hyperchloremia
      due to infusion of high dose of fluids with high concentration of chlorine
      intravenous. Second group received 6882+ 943 ml. of FFP and 6690+882 ml. of
      crystalloids. There was a tendency to metabolic acidosis at the end of anhepatic
      phase pH 7,354+0,061; SBC 22,73+0,94; lactate 3,3+0,98 mmoll/l ;AD 12,85+0,86
      mmol/l and difference difference 1,00+0,048, chlorine 100,76+1,39mmol/l. The main
      factor of metabolic acidosis was increased level of lactate. The third group with
      received 7532+1196ml. of FFP and 3720+629 ml. crystalloids. Metabolic acidosis
      developed at the end of anhepatic period pH 7,346+0,038; SBC21,28+0,95mmol/l;
      lactate 2,72+0,97mmol/l; AD 14,72+0,97mmol/l and difference difference 1,00+0,06;
      chlorine 100,95+2,49mmol/l. The main reason of acidosis was lactate, at the end
      of the operation there was an metabolic alkalosis pH 7,460+0,039; SBC
      29,28+2,63mmol/l; lactate 2,81+1,66mmol/l. CONCLUSION: IVT with equal amount of
      FFP and crystalloids is optimal for liver transplantation surgery because it
      prevents development of metabolic acidosis wich appears due to intravenous
      infusion large dose of crystalloids on the other had it prevent metabolic
      alkalosis at the end of the surgery because of considerable amount of FFP.

PMID- 22379919
TI  - [Clinical assessment of a monitor "MedStorm" (Norway) of galvanic skin response
      correlates with preoperative stress].
AB  - Clinical trials were performed by Russian anesthesiologists of pain monitor based
      on measuring galvanic skin response (skin conductance). 5 pations were studied
      the monitor showed lower sensitivity to assess the level of analgesia during
      combined anesthesia which allows to not recommend it for use in clinical
      practice.

PMID- 22379920
TI  - [Common unsolved anesthetic problems of reconstructive maxillofacial surgery].
AB  - Anesthesia for facial skeleton surgery has been studied. Mane concerns for
      maxillofacial surgery were difficult airways management, poorly controlled
      bleeding, difficult monitoring of several components of anesthesia, duration of
      surgery.

PMID- 22379921
TI  - [Clinical profile and anesthesia during radical operations in patients with burn
      strictures and the esophagus and stomach cancer (literature review)].
AB  - In the review basic problems bound with preoperative period of patients with
      stenosing diseases of an esophagus and a stomach are consecrated. The history of
      development of domestic and foreign surgery of esophagus and stomach is short
      state, features of a preoperative conditions of patients, there preoperative for
      an operative measure are shown. Various techniques of currying out of anesthesia
      and intraoperative monitoring of these patients a current of the early
      postoperative period, structure and character of postoperative complications are
      described.

PMID- 22379922
TI  - [Recruitment maneuver and its effect on hemodynamic in critical ill patient with
      acute lung injury/acute respiratory distress syndrome].
AB  - Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a frequent
      complication in critical ill patients. Recruitment maneuver is rescue procedure
      which improve oxygenation. We confirm improving of oxygenation, decreasing of
      cardiac output and oxygen delivery in monocentral randomized trial.

PMID- 22379923
TI  - [Prevention of acute stress ulcer and gastrointestinal bleeding in patients with
      acute necrotizing pancreatitis].
AB  - We aimed to compare the efficiency of drugs for prevention a gastrointestinal
      bleeding. OBJECTIVE: The results of prospective and retrospective clinical study
      of 51 patients with acute necrotizing pancreatitis ANP. They were distributed
      assigned depending on the drug for the prevention of gastrointestinal bleeding in
      the first group (n = 39) used omeprazole (80 mg/day); in second (n = 12)
      pantoprazole (80 mg/day). The mean age (47,9 +/- 10,6 +/- 9,2) years, the
      severity of disease (average rating of APACHE II classification system 16,7 +/-
      4,5 vs. 14,8 +/- 3,4) were similar. Our data discover that there no statistical
      difference between groups in bleeding rate. CONCLUSION: pantoprazole can be used
      for prevention of hemorrhagic complication of stress ulcer in patients with
      necrotizing pancreatitis. A high percentage of hidden blood loss confirms the
      need for drugs with high therapeutic potential

PMID- 22379924
TI  - [Histologic changes in placenta and chorion of women with antiphospholipid
      syndrome and inherited thrombophilia].
AB  - BACKGROUND: The aim of the study was a histologic evaluation of placentas and
      chorions from pregnancies complicated by antiphospholipid syndrome (APS) and
      inherited thrombophilia in women treated with anticoagulants and in a group of
      women without the anticoagulant treatment. MATERIAL: 24 placentas from 18
      patients with acquired and inherited thrombophilia and 23 chorions from 19
      miscarriages in women with the same diagnosis were included in the study There
      were 33 chorions from miscarriages from healthy women and 25 placentas from
      uneventful pregnancies in the control group. Biopsies from placentas and chorions
      were stained with eosin and hematoxylin and evaluated for the presence of villous
      thrombosis, fibrin deposits, intraplacental hematomas, thrombosis in fetal
      circulation and other histological findings. RESULTS: In the placentas from
      pregnancies complicated with APS and inherited thrombophilia, the presence of
      fibrin deposits in the basal and villous plate, stasis in the fetal circulation
      and thrombosis in the villous plate and villous vessels, were statistically more
      frequent (p < 0,001) comparing with physiological pregnancies. In the material
      from miscarriages the presence of fibrin deposits was statistically more common
      (p < 0,001) in women with thrombophilia. The number of physiological findings in
      placentas of women treated with anticoagulants in pregnancy and in the non
      treated ones, whose pregnancies resulted in fetal demise, were not statistically
      different. CONCLUSIONS: 1. Fibrin deposits between villi and villous plate are
      the most recognizable features in placentas and chorions from APS pregnancies 2.
      In women with APS impaired trophoblast invasion seems to be the most likely cause
      of recurrent miscarriages 3. Anticoagulant therapy does not prevent either fibrin
      deposits collection or other placental changes

PMID- 22379925
TI  - [Risk assessment of chronic HPV HR infection in babies who contacted the virus in
      the perinatal period].
AB  - INTRODUCTION: One of the potential ways of HPV transmission to fetuses and
      newborns is a direct perinatal infection, manifested as juvenile laryngeal
      papillomatosis (JLP). This applies to children after traditional birth, born to
      mothers in whom the DNA sequences of the HPV HR in the paraepidermal epithelium
      of cervix were found during pregnancy and delivery OBJECTIVES: Risk assessment of
      the development of chronic HPV HR infection in babies who had contact with the
      virus in the perinatal period. MATERIALS AND METHODS: During the pre- and
      perinatal period, research was carried out among 185 pregnant women and a group
      of 105 newborns (5 pairs of twins), hospitalized in the Delivery Room of the
      Gynecology and Obstetrics Clinic of the Poznan Medical University between 2005
      2007. Cellular material from the uterine cervical canal using a brush-type Cervex
      Brush was collected from each woman participating in the study and oral swabs
      using swab sticks were taken from the newborns. The second phase of testing was
      conducted following the postpartum, 3 to 6 months after the delivery Uterine
      cervix swabs were re-collected from 28 HPV HR positive women and swab from the
      mouth and nasopharynx were taken from their children (29 samples--1 pair of
      twins). The study was conducted with the use of PCR, trade named AMPLICOR Human
      Papilloma Virus (HPV) Test by Roche. RESULTS: DNA HPV HR was found in 55 cases of
      the cellular material derived from 185 swabs taken from the cervical canal,
      representing 29.7% of researched women. The chronic HPV HR viral infection was
      detected in 25 cases out of the 28 HPV HR positive women, representing 89.2% of
      the study group. Of the 105 infants from whom oral swabs were taken in the
      perinatal period, presence of DNA HPV HR was found in 2 infants (2%) after
      traditional birth. Whereas the repeated test, within 3-6 months after delivery
      revealed the presence of DNA HPV HR viruses in swab oral in 1 infant, who had
      been DNA HPV HR positive. CONCLUSIONS: Perinatal transmission of Human
      Papillomavirus of the high-risk oncogenic type is rare and concerns below 2% of
      babies of HPV HR positive mothers. Prolonged infection by the Human
      Papillomavirus is an extremely rare complication of pregnancy and delivery and
      concerns below 1% of children of HPV HR positive mothers. Perinatal transmission
      of the oncogenic type infection of the virus in humans is primarily of the
      ascending type or occurs during the perinatal period if the delivery was a
      traditional one.

PMID- 22379926
TI  - Evaluation of HPV DNA HR assay in females as a marker of recurrent disease
      following treatment of cervical intraepithelial neoplasia.
AB  - AIM: The basic assumption of the prevention of cervical cancer is to early detect
      and treat CIN (cervical intraepithelial neoplasia) as well as to prevent
      recurrence of neoplasia after therapy This study involved comparison of the
      cytology test value and determination of HPV (human papilloma virus) DNA in women
      treated for CIN so as to find a sensitive and specific marker of disease
      recurrence. METHODS: A group of 107 females after CIN treatment underwent 14
      month follow-up and regular cytological and molecular evaluations. RESULTS: Based
      on the follow-up data the recurrence of CIN was found in 9 females who despite
      effective therapy for the entire follow-up period were HPV positive. Evaluation
      of value of HR (high risk)--HPV DNA assay used to detect CIN showed its 100%
      sensitivity CONCLUSION: The HR-HPV DNA assay is likely to be a valuable
      diagnostic tool facilitating more precise detection of recurrent neoplasia risk
      than cytological test alone.

PMID- 22379927
TI  - Management of the stressful stigma attached to sexually transmitted disease
      (preliminary report).
AB  - BACKGROUND: Syphilis and other sexually transmitted diseases may cause some
      psychological problems and anxiety among the infected patients. OBJECTIVES: The
      aim of the study was to examine the differences in stress level and stress coping
      strategies of patients infected with syphilis and healthy controls. Also, the
      authors aimed at establishing types of strategies to cope with the stigma of
      sexually transmitted diseases. MATERIAL AND METHODS: The study was a survey of 21
      syphilis infected subjects and 21 healthy subjects, paired according to age and
      gender The respondents used the SRRS questionnaire with some additional questions
      and the Mental Adjustment to Disease Mini-MAC Scale in Polish adapted version.
      The latter was given to the syphilis-infected subjects only RESULTS: The syphilis
      infected subjects experienced more acute stress than the healthy subjects. Most
      healthy subjects used the active task strategy to cope with stress while the
      infected subjects (particularly females) chose the escape strategy and the
      'waiting out' strategy The infected males preferred an active style of coping
      with the stigma; among the females, the anxiety style was dominant. CONCLUSIONS:
      Syphilis is a source of permanent stress and awareness of the possible social
      consequences is a strong stimulus, prompting the stigma bearer to keep its
      existence a secret.

PMID- 22379928
TI  - [Usefulness of MLPA technique for rapid prenatal detection of aneuploidy. Results
      of 409 diagnostic studies].
AB  - OBJECTIVES: The study was aimed to determine diagnostic application of MLPA for
      rapid prenatal identification of chromosome 13, 18, 21 and X and Y aneuploidies.
      MATERIAL AND METHODS: 409 amniotic fluid samples from amniocentesis for fetal
      karyotyping were studied. DNA was isolated using the QIAmp DNA Blood Midi Kit
      (348 samples) or through proteinase K treatment (61 samples). SALSA MLPA P095
      probes (mrc-Holland) were used to detect aneuploidy RESULTS: In 324 studies
      (79.2%) diagnostic results were obtained. Chromosomal aberrations were found in
      16 cases (4.9%). These results were concordant with standard karyotype. In 3
      cases (0.92%) false negative results were found but all abnormalities were
      undetectable with MLPA. CONCLUSIONS: MLPA is a reliable method of rapid prenatal
      detection of aneuploidy

PMID- 22379929
TI  - [Contemporary management of neuroendocrine neoplasms of the female genital
      organs].
AB  - Neuroendocrine neoplasms are a rare and heterogeneous group of diseases that
      account for only 2% of all gynecologic malignancies. The most common types are
      ovarian carcinoid tumor and small cell neuroendocrine carcinoma of the cervix.
      The tumors are staged according to FIGO clinical staging system. The diagnosis is
      usually made retrospectively after obtaining the results of histopathological
      evaluation of the primary tumor They rarely cause syndromes related to hormone
      overexpression. Neuroendocrine neoplasms are characterized by aggressive
      behaviour Even at an early stage there is high incidence of nodal and distant
      metastases. Survival is poor regardless of stage at diagnosis. The most important
      is to diagnose the neuroendocrine tumor accurately and treat it in multimodal,
      aggressive approach to control the disease better and reduce the incidence of
      reccurences. Apart from typical therapeutic approach, treatment may encompass
      isotope therapy using radiolabeled somatostatin analogs. This method should be
      reserved for patients with expression of somatostatin receptors detected by the
      somatostatin receptor scyntygraphy. Data concerning the management of
      neuroendocrin tumors are based mainly on retrospective studies and clinical case
      series. Lack of randomized trials makes it impossible to select the best
      treatment option. Better understanding of the biology of neuroendocrine tumors,
      especially the molecular genetics, will in the future help to determine the
      optimal treatment strategies for these tumors.

PMID- 22379930
TI  - [Intracrinology and dehydroepiandrosterone--a new perspective for the use of
      androgens in hormone replacement therapy in postmenopausal women].
AB  - During menopausal transition not only ovarian production of estrogens but also
      marked decrease of adrenal androgen production are observed Decreased secretion
      of adrenal DHEA and DHEA-S result in reduction of peripheral conversion of these
      steroids into active estrogens and androgens. Intracrinology describes the
      biosynthesis of active steroids in peripheral target tissues in which the action
      of theses steroids takes place, without release into the extracellular space or
      general circulation. DHEA administration to postmenopausal women significantly
      increases bone mineral density decreases insulin resistance and amount of fat
      tissue and exerts an estrogenic effect on vaginal cytology in the absence of
      endometrial stimulation. Moreover animal experiments proved that DHEA suppresses
      the growth of breast cancer which is yet another reason to consider this steroid
      as a part of hormone replacement therapy in women.

PMID- 22379931
TI  - [Fertility-conserving therapy in cervical cancer patients].
AB  - Treatment of the cervical cancer patients, especially young women, is a very
      important clinical problem. This is related to the standard treatment methods,
      used in this malignancy and the treatment complications. In most patients, the
      oncological treatment, be it surgery or radiotherapy results in gonadal
      dysfunction with unavoidable loss of the ability to procreate. As cervical cancer
      affects mostly young women, fertility preserving treatment remains a considerable
      challenge. Due to the fact that the recent decade has brought significant
      progress in the diagnosis of prognostically important features characterizing the
      tumor biology their precise determination enables specialists to detect a
      subpopulation of patients with malignancies, who do not require the total
      resection of the uterus and ovaries. Currently in such cases, fertility-sparing
      surgery is considered in every young woman with early cervical cancer who wishes
      to preserve the reproductive function. The aim of the paper is to revive the
      current opinions concerning fertility sparing treatment options in gynecological
      malignancies.

PMID- 22379932
TI  - [First trimester diagnosis of encephalocele--report of two cases and review of
      the literature].
AB  - The authors present two cases of encephalocele, diagnosed at 11(+0)-13(+6) wks
      scan. Case 1: Occipital encephalocele (max diameter 14 mm) without brain tissue
      was diagnosed at 12 wks. At 35 wks bilateral ventriculomegaly was additionally
      found. The course of pregnancy was uneventful. Encephalocele was closed
      surgically soon after delivery Normal neonatal development at 6 months of age was
      confirmed. Case 2: Occipital encephalocele (max diameter 34 mm) containing brain
      tissue was diagnosed at 12 wks. Two weeks later fetal demise was confirmed during
      ultrasound examination. Uncomplicated induction of abortion was performed
      locally. The outcome and possible clinical scenarios in both cases, together with
      review of literature, are presented in the article.

PMID- 22379933
TI  - Two histologically different tumours in a neonate born from an assisted
      reproductive technology pregnancy.
AB  - The first case of a female neonate born from an in vitro fertilization with
      embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) (IVF-ET
      (ICSI) with two histologically different tumours (craniopharyngioma and
      hepatoblastoma) is described. Anti-neoplasmatic therapy was abandoned due to the
      significant extent of the disease (craniopharyngioma, 15 x 12 cm in diameter with
      active internal hydrocephalus; and right liver lobe hepatoblastoma, 5 cm in
      diameter) and the severely impaired general condition of the neonate. The neonate
      died on the 30th day of life due to cerebellar and brainstem herniation, followed
      by circulatory and respiratory failure.

PMID- 22379934
TI  - [Nonimmune hydrops fetalis associated with congenital small bowel atresia--a case
      study].
AB  - Nonimmune hydrops fetalis is observed with the frequency of 1:3000 cases
      diagnosed pre- and postnatally. In the following paper the authors analyzed the
      course of pregnancy complicated by fetal ascites and polyhydramnios with the
      appearance of colonic ileus and they presented the postnatal condition of the
      baby The preliminary diagnosis was confirmed after birth and the newborn was
      operated in the second day of his life. The congenital small bowel atresia was
      qualified as a III B type (Grossfeld qualification), which is called the "pagoda"
      syndrome [3]. The colonic atresia is located then around the superior mesenteric
      vessels, which leads to colonic necrosis (Figure 1).

PMID- 22379935
TI  - [Antioxidative system in pregnant women infected by Chlamydia trachomatis,
      Mycoplasma hominis, Ureaplasma urealyticum].
AB  - OBJECTIVES: The study was performed to evaluate the frequency of cervical
      infections with Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma
      hominis in women with normal pregnancy and with symptoms of spontaneous abortion
      or preterm delivery. Antioxidant status of pregnant women was assessed. Elevated
      oxidative status is claimed to be one of the factors causing threatened
      miscarriage and premature labor. MATERIAL AND METHODS: From 73 women endocervical
      culture was investigated for Chlamydia trachomatis (method of rRNA
      Hybridization), Ureaplasma urealyticum and Mycoplasma hominis (Mycoplasma IST 2
      test). Gestational age ranged from 14-30 weeks. They were categorized into 2
      groups: patients not presenting these symptoms without history of pregnancy
      complications and patients with threatened abortion or symptoms of preterm
      delivery Following oxidative status factors were measures: Superoxide Dysmutase,
      Catalase and Glutathion Peroxidase in blood and saliva of 49 pregnant women of
      both groups were elevated. Statistica: the Student's T test, chi-square test, U
      Manna-Whithney's test. RESULTS: The results show difficulty in assessment of
      direct influence of Chlamydia infection on oxidative stress. Ch. trachomatis was
      present in 9.6%, M. hominis in 6.8%, U. urealyticum in 28.8% of vaginal cultures.
      Chlamydiasis statistically increases production of Reactive Oxygen Forms what
      results in unfavorable outcome of the pregnancy Increase of the following
      parameters was observed: Superoxide Dysmutase (5583.2 vs 8980.2U/ml/sec) and
      Catalase (15.1 vs 18.3U/ml/sec). CONCLUSION: Infection of Chlamydia trachomatis
      could be a significant factor in pathogenesis of threatened abortion and preterm
      delivery as it increases oxidative stress.

PMID- 22379936
TI  - [Analysis of the course of pregnancy and labor after genetic amniocenthesis in
      women after 35 years of age].
AB  - THE PURPOSE OF THE RESEARCH: Analysis of the course of pregnancy and labor in
      patients qualified for the prenatal diagnostic tests program in Opole Region.
      MATERIAL AND METHODS: 2513 pregnant women participated in the program. There were
      1763 (70.1%) patients above 35 years of age, out of whom 515 women (20.5%) were
      qualified for amniocentesis and 394 of them (15.6%) decided to undergo the test.
      Within the group of patients who underwent amniocentesis, 39 karyotypes (9.8%)
      were found. Analysis of the number of amniocenteses carried out and the number of
      detected fetal defects showed that initially the number of invasive tests was
      rising. However since 2007, i.e. since the introduction of biochemical diagnostic
      tests based on Kryptor technology a significant decrease of amniocenteses tests
      has been observed, while the rate of detected chromosome aberrations in fetuses
      has not changed. The course of pregnancy and labor in patients above 35 years of
      age, who gave birth to children in Gynecology and Obstetrics Hospital in Opole,
      has also been analyzed. The investigated group comprised 106 patients who
      underwent amniocentesis, and 138 patients who did not consent to having the
      invasive test. Apart from a small difference in average birth weight, the
      analysis of infant condition and their biophysical parameters after the labor has
      not shown any significant differences. In both groups gestational diabetes was
      the most frequent disease, and statistically it was diagnosed more often in
      patients who had not undergone amniocentesis. No statistically significant
      differences in the frequency of occurrence of other pregnancy complications have
      been found. CONCLUSIONS: 1. Amniocentesis carried out due to genetic indications
      between 150th and 20th week of pregnancy may be considered to be a procedure
      which is safe both for a mother and a fetus. 2. Amniocentesis does not affect the
      course of pregnancy or the mode of delivery in any significant way. 3. Proper
      genetics counseling service based on biochemical research enables to decrease the
      number of amniocenteses tests, while the rate of detected chromosome defects in
      fetuses remains unchanged.

PMID- 22379937
TI  - [Endometrioid endometrial cancer--the prognostic value of selected clinical and
      pathological parameters].
AB  - OBJECTIVES: To assess the relationship between selected clinical and pathological
      factors and disease free survival (DFS) and overall survival (OS) in endometrioid
      endometrial cancer patients. MATERIAL AND METHODS: A retrospective review of 262
      patients aged 37-86 (6.0 +/- 9.0) was performed. Selected clinical and
      pathological data were correlated with DFS and OS. RESULTS: Follow-up was 8-123
      months (64.9 +/- 27.1). In 4 patients (1.5%) clinical progression was diagnosed
      during the treatment. In 43 patients (16.4%) relapse was diagnosed 2-61 months
      (23.9 +/- 15.7) after commencing treatment. DFS and OS were 82.1% and 81.3%
      respectively. In univariate analysis worse DFS was related to older patients (p =
      0.007) and non-radical surgery (p < 0.001). In multivariate analysis worse DFS
      was related to older patients (HR = 1.058; 95% CI = 1.024-1.093; p < 0.001),
      younger at menopause (HR = 0.910; 95% CI = 0.851-0.973; p = 0.006), with higher
      staging (HR = 2.639; 95% CI = 1.968-3.539; p < 0.001) operated non-radically (HR
      = 0.220; 95% CI = 0.096-0.504; p < 0.001). In univariate analysis worse OS was
      connected with older patients (p = 0.018), diabetes type II (p = 0.019) and non
      radical surgery (p < 0.001). In multivariate analysis worse OS was related to
      younger age at menopause (HR = 0.932; 95% CI = 0.873-0.996; p = 0.039), diabetes
      type II (HR = 2.372; 95% CI = 1.260-4.466; p = 0.008), higher staging (HR =
      2.053; 95% CI = 1.482-2.845; p < 0.001), and non-radical surgery (HR = 0.240; 95%
      CI = 0.091-0.636; p = 0.004). CONCLUSIONS: Relapsed endometrial cancer developed
      in 90.7% during four years after commencing treatment. In 79.1% of these patients
      distant metastases were present. Most significant prognostic factors were
      radicality of surgery age of patients and staging. The presence of diabetes type
      II and early menopause were connected with worse prognosis.

PMID- 22379938
TI  - [Frequency of antiphospholipid syndrome in women with pregnancy loss in
      multicenter study in Poland].
AB  - THE AIM: The aim of the study was the analysis of antiphospholipid syndrome
      frequency in Polish women with pregnancy loss. MATERIAL AND METHODS: We analyzed
      352 women with average age of 31.4 (+/- 4.3) who experienced one or more
      pregnancy losses. Patients from 5 University centers: Poznan, Bialystok, Lublin,
      Wroclaw and Bydgoszcz were divided into 3 groups. In the 1st group there were 150
      women with recurrent early pregnancy losses before 10 weeks gestation, in the 2nd
      group we included 160 women with late pregnancy losses, in the 3rd group we
      analyzed 42 women with labor complicated by preeclampsia or placental
      insufficiency within or before 34 gestational week. All 352 women were screened
      for the presence of anticardiolipin antibodies (aCL), anti beta2glikoprotein I
      (abeta2GPI) and lupus anticoagulant (LA). The first two antibodies were
      investigated with ELISA test and the last one with APPT based test. Only the
      second positive result qualified patients as antiphospholipid antibody (aPL)
      positive. Antibodies against cardiolipin and beta2glicoprotein I were analyzed in
      three classes--IgA, IgG and IgM--where the laboratory criteria of positivity were
      titers above 40 unitsU/ml or above 99 centile. RESULTS: 13 patients (3.69%) in
      the screened population of 352 women met the criteria of the antiphospholipid
      syndrome. The frequency of APS in women with early and late pregnancy losses were
      1.33% and 6.25%, respectively. The most common antibody found was lupus
      anticoagulant (LA). In 3 women with late pregnancy loss all three antibodies were
      found. In women with premature deliveries complicated with preeclampsia and/or
      placental insufficiency the frequency of APS was 2.58%. CONCLUSION: 1. Screening
      of antiphospholipid syndrome should be routinely performed in women with late
      pregnancy loss 2. We can conclude that APS is rarely found in women with
      pregnancy loss before 10 gestational week.

PMID- 22379939
TI  - [Analysis of the odds ratio for developing breast cancer in women].
AB  - Malignant breast cancer is the most common neoplasm in women in most developed
      countries. The majority of cases of breast cancer are probably connected with
      environmental factors and lifestyle. According to the current state of knowledge,
      modification of risk factors may contribute to the reduction of breast cancer
      cases and individual assessment performed by selecting a group of women with
      increased risk may help to reduce mortality. The purpose of the study was to
      analyze risk factors affecting the increase of odds ratio (OR) for developing
      breast cancer and to define in which range OR increases or decreases
      significantly. The participants of the study were healthy women with no changes
      in mammary glands and women with breast cancer diagnosed on the basis of
      histopathological examination. The study was carried out in Great Poland and
      Lubuskie province between 2005 and 2006. The total number of participants was 371
      females, aged 35-70 years. The highest risk of breast cancer was observed in
      women over 55, BMI > 30, who had > 5 deliveries, with cancer family history and
      suffering from severe depression. Apart from cancer family history all other
      factors are potentially modifiable. Appropriate education of women can result in
      reduction of breast cancer risk.

PMID- 22379940
TI  - Plasma homocysteine concentrations in mothers and term and preterm newborns.
AB  - AIM: To assess the correlation between homocysteine concentrations and
      gestational age, gender Apgar score, complications in pregnancy delivery
      modalities and levels of vitamin B12 and foliate. MATERIAL AND METHODS:
      Concentration of homocysteine, vitamins-B12, foliate were measured in cord blood
      and mother blood. There were 40 full-term babies and 38 preterm babies and their
      mothers. RESULT: The homocysteine concentration in newborns correlated with
      homocysteine level in mothers. There was no difference in homocysteine level
      regardless of newborns gender. There was no correlation in the homocysteine
      concentration of mothers blood and cord blood with the levels of vitamin 812 and
      foliate. In full-term newborns a significant increase in homocysteine levels in
      comparison with premature babies was observed (7.2 +/- 1.4 micromol/ vs. 6.4 +/-
      1.3 micromo/l; p = 0.01). Additionally negative correlation between the mothers'
      age and homocysteine concentration (r = -0.23; p = 0.04) and positive correlation
      between homocysteine concentration in cord plasma and gestation age (r = 0.28; p
      = 0.01) were found. CONCLUSION: Homocysteine concentration depends on gestational
      age, Apgar score and mother's age. There is no correlation between homocysteine
      level and hypertension during pregnancy type of delivery levels of vitamin 812
      and foliate. Determination of homocysteine level is therefore of no significant
      importance in newborns pathophysiology.

PMID- 22379941
TI  - [Method of analgesia for labor in relation to newborn condition, cord blood
      cortisol and interleukin-6 levels].
AB  - AIM OF THE STUDY: To assess the impact of various forms of intrapartum analgesia
      on birth condition of the newborn. MATERIAL: The study included 109 newborns,
      among them 23 from mothers who received intravenous patient-controlled analgesia
      (PCA) using remifentanil (0.2 microg/kg per dose), 31 infants from mothers
      treated with PCA epidural anesthesia with fentanyl and 0.125% bupivacaine, 34
      newborns from mothers treated with pethidine analgesia given on an ad hoc basis
      at a dose of 50 mg by intramuscular injection, and 21 newborns from mothers who
      did not use any form of anesthesia. METHODS: The birth condition was evaluated in
      all infants by Apgar score and umbilical artery blood gases. In the blood from
      the umbilical vein the concentration of cortisol and interleukin-6 were
      evaluated. RESULTS AND CONCLUSIONS: The use of epidural analgesia with
      bupivacaine as well as pethidine given intramuscularly did not impair the status
      of newborn evaluated on the basis of Apgar score, however, it adversely modifies
      the pH and umbilical artery blood pCO2. No additional beneficial effect of
      anesthesia using remifentanil intravenous PCA method on newborn status assessed
      on the basis of the value of Apgar score and acid-base balance of umbilical
      artery blood was found and it does not allow to recommend this form of anesthesia
      as surpassing the existing methods of intrapatum analgesia. The concentration of
      cortisol and interleukin-6 in umbilical cord blood is not related with the type
      of maternal intrapartum analgesia.

PMID- 22379942
TI  - [Premature rupture of membranes one fetus from a multiple pregnancy].
AB  - In multiple gestation, premature rupture of fetal membranes (PROM) is an
      important risk factor for premature delivery and intrauterine infection. The
      incidence of PROM in twin gestations is threefold of that in singleton
      pregnancies. The incidence in triplets occurs even more frequently underlining
      the role of PROM as a leading cause of infant mortality and morbidity. Besides
      prematurity the complications of PROM include umbilical cord compression due to
      oligohydramnios, cord prolapse, placental abruption, and chorioamnionitis.
      Together with PROM, chorioamnionitis is held responsible for significant maternal
      and neonatal morbidity including endometritis and sepsis in the mother and early
      onset sepsis, respiratory distress syndrome, inborn pneumonia, bronchopulmonary
      dysplasia, intraventricular hemorrhage, and periventricular white matter injury
      in the neonate. Furthermore, in twin gestations, PROM remains an independent risk
      factor for long-term neonatal care. An uncommon situation develops when in
      multiple gestation PROM affects only one of the fetuses. In such cases, the co
      existence in the uterine cavity of the properly developing fetus(es) can be a
      challenge for the process of medical decision-making. In the present work,
      limited world literature on the topic was critically reviewed in search of the
      best possible recommendations for clinical management.

PMID- 22379943
TI  - [Tethered vagina syndrome after classical anterior colporrhaphy].
AB  - We presented etiology symptomatology and diagnosis of the tethered vagina
      syndrome. Detailed information concerning pharmacological and surgical treatment
      was given. Surgical method of vaginal anatomy restoration using Martius flap
      technique was described in patients with tethered vagina syndrome after classical
      anterior colporrhaphy. We paid special attention to a particular type of genital
      fibrosis such as labial fusion in girls.

PMID- 22379944
TI  - [Pregnancy in a patient with resistant ovary syndrome--a case report].
AB  - Resistant ovary syndrome (ROS) and premature ovarian failure (POF) represent two
      forms of hypergonadotropic hypogonadism. Principal symptoms include primary or
      secondary amenorrhea (before the age of 40 years), low levels of estradiol and
      elevated FSH (above 40IU/ml) in serum. The main difference is the presence of
      follicles in ROS which is tantamount to the possibility of pregnancy. We present
      the case of pregnancy in a 31-year-old patient who was initially diagnosed with
      POF, which was the basis of the final diagnosis of ROS.

PMID- 22379945
TI  - Successful complex management of a congenital diaphragmatic hernia--a case
      report.
AB  - Congenital diaphragmatic hernia is a very serious congenital defect associated
      with high mortality rate. The syndrome is characterized by migration of abdominal
      viscera to thoracic cavity a variable degree of pulmonary hypoplasia associated
      with pulmonary hypertension caused by alteration of pulmonary vessels diameter
      increased muscularisation of pulmonary arteries and decreased compliance of the
      lungs resulting in increased afterload of the right ventricle, decreased cardiac
      output and impaired oxygenation. We describe a case of congenital diaphragmatic
      hernia with migration of the stomach, the small and the large bowels and the left
      hepatic lobe into the left pleural space, diagnosed by ultrasound in utero at 24
      weeks of gestation. The child was initially placed on high-frequency oscillation
      and nitric oxide and required vigorous inotropic support. The defect was repaired
      after stabilization of the cardiac output and gas exchange. The patient made
      successful recovery.

PMID- 22379946
TI  - [Polish Gynecological Society Expert Committee recommendations regarding
      application of Chela-Mag B6 Mama in obstetrics and gynecology].

PMID- 22379947
TI  - Importance of correct prediction of initial concentrations in voltammetric scans:
      contrasting roles of thermodynamics, kinetics, and natural convection.
AB  - In order to successfully model an electrochemical reaction mechanism one must
      ensure that all the equations, including initial conditions, satisfy the
      pertinent thermodynamic and kinetic relationships. Failure to do so may lead to
      invalid results even if they are mathematically correct. This fact has been
      previously emphasized (Luo, W.; Feldberg, S. W.; Rudolph, M. J. Electroanal.
      Chem. 1994, 368, 109 - 113; Rudolph, M. Digital Simulation in Electrochemistry.
      In Physical Electrochemistry; Rubenstein, I., Ed.; Marcel Dekker: New York, 1995;
      Chapter 3) and existing computer software for electrochemical simulations, such
      as DigiSim (Rudolph, M.; Reddy, D. P.; Feldberg, S. W. Anal. Chem. 1994, 66,
      589A; http://www.basinc.com/products/ec/digisim/), offer the option of enforcing
      the so-called "pre-equilibration" which evaluates thermodynamic concentrations of
      all species prior to beginning a voltammetric scan. Although this approach allows
      setting consistent thermodynamic values it may result in a nonrealistic initial
      concentrations set because it corresponds to the whole solution status at
      infinite time for infinite kinetic constants. However, the perturbation created
      by the working electrode poised at its rest potential is necessarily limited by
      the size of the electrode, reaction kinetics, and duration of the rest period.
      Furthermore, natural convection limits even more the importance of the
      perturbation. This is analyzed theoretically through comparison of simulation
      results by DigiSim and KISSA-1D software for certain common electrochemical
      mechanisms in order to illustrate the importance of correct prediction of initial
      concentrations.

PMID- 22379948
TI  - Chemical constituents of Indonesian plant Protium javanicum Burm. f. and their
      antifeedant activities against Coptotermes formosanus Shiraki.
AB  - In the continuing study of antifeedant compounds in Protium javanicum Burm. f.
      against Coptotermes formosanus Shiraki, 6-desacetylnimbin (1), quercitrin (2) and
      myricitrin (3) were isolated from P. javanicum extract. All compounds were
      characterised by NMR and MS. Furthermore, the structure of 6-desacetylnimbin was
      confirmed by X-ray crystallography. The antifeedant activity was evaluated with
      no-choice feeding tests. At a dose of 0.5 mg, 6-desacetylnimbin exhibited the
      highest antifeedant activity among the isolates.

PMID- 22379949
TI  - A meta-analysis of white matter changes in temporal lobe epilepsy as studied with
      diffusion tensor imaging.
AB  - PURPOSE: Diffusion tensor imaging (DTI) is used increasingly to study white
      matter integrity in people with temporal lobe epilepsy (TLE). Most studies report
      fractional anisotropy (FA) decrease and mean diffusivity (MD) increase in
      multiple white matter regions. The disturbance of white matter integrity varies
      across studies and between regions. We aimed to obtain a more consistent estimate
      of white matter diffusion characteristics and relate these to the distance from
      the seizure focus. METHODS: Studies comparing diffusion characteristics of people
      with epilepsy with those of healthy controls were systematically reviewed and
      quantified using random and mixed effects meta analysis. In addition to the
      overall meta-analysis, pooled FA and MD differences were determined per
      hemisphere and white matter category separately. KEY FINDINGS: We included 13
      cross-sectional studies. The pooled FA difference for all white matter was -0.026
      (95% confidence interval [CI] -0.033 to -0.019) and MD difference was 0.028 * 10(
      3) mm(2)/s (95% CI 0.015-0.04). FA was reduced significantly in people with TLE
      compared with healthy controls in both ipsilateral (mean difference -0.03) and
      contralateral white matter (-0.02). MD was significantly increased ipsilaterally
      and contralaterally. MD differed significantly between white matter connected to
      the affected temporal lobe and remote white matter. SIGNIFICANCE: The meta
      analysis provides a better estimation of the true diffusion characteristics.
      White matter structural integrity in TLE is disturbed more severely in the
      ipsilateral than in the contralateral hemisphere, and tracts closely connected
      with the affected temporal lobe are most disturbed. The exact underlying
      mechanisms remain to be elucidated.

PMID- 22379950
TI  - Eukaryotic translation initiation factor 4E-mediated recessive resistance to
      plant viruses and its utility in crop improvement.
AB  - The use of genetic resistance is considered to be the most effective and
      sustainable approach to the control of plant pathogens. Although most of the
      known natural resistance genes are monogenic dominant R genes that are
      predominant against fungi and bacteria, more and more recessive resistance genes
      against viruses have been cloned in the last decade. Interestingly, of the 14
      natural recessive resistance genes against plant viruses that have been cloned
      from diverse plant species thus far, 12 encode the eukaryotic translation
      initiation factor 4E (eIF4E) or its isoform eIF(iso)4E. This review is intended
      to summarize the current state of knowledge about eIF4E and the possible
      mechanisms underlying its essential role in virus infection, and to discuss
      recent progress and the potential of eIF4E as a target gene in the development of
      genetic resistance to viruses for crop improvement.

PMID- 22379951
TI  - Numerical errors and chaotic behavior in docking simulations.
AB  - This work examines the sensitivity of docking programs to tiny changes in ligand
      input files. The results show that nearly identical ligand input structures can
      produce dramatically different top-scoring docked poses. Even changing the atom
      order in a ligand input file can produce significantly different poses and
      scores. In well-behaved cases the docking variations are small and follow a
      normal distribution around a central pose and score, but in many cases the
      variations are large and reflect wildly different top scores and binding modes.
      The docking variations are characterized by statistical methods, and the
      sensitivity of high-throughput and more precise docking methods are compared. The
      results demonstrate that part of docking variation is due to numerical
      sensitivity and potentially chaotic effects in current docking algorithms and not
      solely due to incomplete ligand conformation and pose searching. These results
      have major implications for the way docking is currently used for pose
      prediction, ranking, and virtual screening.

PMID- 22379952
TI  - Mental health first aid guidelines: an evaluation of impact following download
      from the World Wide Web.
AB  - AIM: Mental health first aid guidelines provide the public with consensus-based
      information about how to assist someone who is developing a mental illness or
      experiencing a mental health crisis. The aim of the current study was to evaluate
      the usefulness and impact of the guidelines on web users who download them.
      METHOD: Web users who downloaded the documents were invited to respond to an
      initial demographic questionnaire, then a follow up about how the documents had
      been used, their perceived usefulness, whether first-aid situations had been
      encountered and if these were influenced by the documents. RESULTS: Over 9.8
      months, 706 web users responded to the initial questionnaire and 154 responded to
      the second. A majority reported downloading the document because their job
      involved contact with people with mental illness. Sixty-three web users reported
      providing first aid, 44 of whom reported that the person they were assisting had
      sought professional care as a result of their suggestion. Twenty-three web users
      reported seeking care themselves. A majority of those who provided first aid
      reported feeling that they had been successful in helping the person, that they
      had been able to assist in a way that was more knowledgeable, skilful and
      supportive, and that the guidelines had contributed to these outcomes.
      CONCLUSIONS: Information made freely available on the Internet, about how to
      provide mental health first aid to someone who is developing a mental health
      problem or experiencing a mental health crisis, is associated with more positive,
      empathic and successful helping behaviours.

PMID- 22379954
TI  - Synthesis and facet-dependent photoreactivity of BiOCl single-crystalline
      nanosheets.
AB  - BiOCl single-crystalline nanosheets with exposed {001} and {010} facets were
      selectively synthesized via a facile hydrothermal route. The resulting BiOCl
      single-crystalline nanosheets with exposed {001} facets exhibited higher activity
      for direct semiconductor photoexcitation pollutant degradation under UV light,
      but the counterpart with exposed {010} facets possessed superior activity for
      indirect dye photosensitization degradation under visible light.

PMID- 22379953
TI  - Changes in utilization and costs for patients with rheumatoid arthritis, 1997 to
      2006.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that often
      results in joint pain, inflammation and bone erosions. Perhaps the most notable
      change in RA treatment during the last decade is the advent of biologics, and, in
      particular, anti-tumour necrosis factor agents. Given these advances, it is
      useful to assess how healthcare and work-loss costs of patients with RA have
      changed. OBJECTIVE: Our objective was to assess changes in healthcare utilization
      and costs from 1997 to 2006 for patients diagnosed with RA. METHODS: Two cohorts
      (1997 and 2006) of patients with RA and matched controls were identified from two
      administrative claims databases along with subsamples of employed patients and
      matched controls. The analysis focused on the more homogeneous employee
      subsample. We compared annual excess co-morbidity rates, resource utilization and
      healthcare and work-loss costs per patient between the 1997 (n = 279) and 2006
      cohorts (n = 837) with difference-in-differences methodology. Results with p <
      0.05 were considered statistically significant. RESULTS: In the employee
      subsample, there were no statistically significant differences in the excess
      prevalence of non-RA co-morbidities or Charlson Co-morbidity Index results,
      except for cardiovascular disease, which decreased by 11.1%. Excess number of ED
      visits and days hospitalized decreased by 1.1 visits/patient and 0.9
      days/patient, respectively, while rheumatologist visits increased by 0.9
      visits/patient. Excess per-patient direct costs were unchanged. However, drug
      costs increased by $US633/patient, but medical costs decreased by $US618/patient
      (not significant) [year 2006 values]. CONCLUSION: For employed patients with RA,
      there were significant reductions in per-patient excess hospital days, as well as
      ED visits, and no changes in excess total direct costs over time. New treatments
      introduced during the study period may be associated with cost savings that
      offset changes in employee utilization of drug and medical services. In addition,
      the reductions in excess ED visits and hospital days suggest improvements in
      patient quality of life.

PMID- 22379955
TI  - Fulminant hepatitis A infection in second trimester of pregnancy requiring living
      donor liver transplantation.
AB  - We present an 18-year-old pregnant woman who was referred to our emergency clinic
      as a case of acute hepatic failure and hepatic encephalopathy. Laboratory tests
      showed abnormal liver function tests and serological workup was consistent with
      acute hepatitis A infection. Ultrasonography revealed a single live fetus with
      fetal biometry compatible with 18 gestational weeks. The patient underwent a
      highly urgent liver transplantation using a right lobe graft from her husband.
      Histological examination of the explanted liver showed acute, lymphocyte-rich,
      diffuse necrotizing hepatitis, consistent with acute necrotizing hepatitis A.
      After the operation her allograft function gradually recovered. Her follow-up
      obstetrics ultrasound revealed a male fetus with severely decreased amniotic
      fluid. The patient was informed about the poor prognosis of her pregnancy and the
      pregnancy was terminated by vaginal misoprostol induction. She has maintained a
      good general condition and liver function for 4 months postoperatively, up to the
      present time.

PMID- 22379956
TI  - Heterologous expression of bacterial nitric oxide synthase gene: a potential
      biological method to control biofilm development in the environment.
AB  - The nitric oxide synthase gene from  Bacillus subtilis  was heterologously
      expressed in  Pseudomonas putida  using a broad-host expression vector. Both the
      performance of the nitric oxide-specific fluorescent probe and the quantitative
      assessment of the nitric oxide end products demonstrated the generation of nitric
      oxide. The endogenous nitric oxide increased the motility of P. putida and
      decreased the capacity of P. putida and other multispecies bacteria to develop
      biofilms. On the practical side, endogenous nitric oxide offers an advantage in
      generating continuous, controllable levels of nitric oxide, which suggests a new
      method to use nitric oxide in the control of biofilms.

PMID- 22379958
TI  - How molecular diagnosis can change allergen-specific immunotherapy prescription
      in a complex pollen area.
AB  - BACKGROUND: The identification of disease-eliciting allergens is a prerequisite
      for accurate prescription of allergen-specific immunotherapy (SIT). The aim of
      this study was to determine whether molecular diagnosis (MD) may change
      indication and allergen prescription of SIT. METHODS: A total of 141 patients
      with allergic rhinoconjunctivitis and/or asthma sensitized to pollen with or
      without concomitant food allergy were included. Skin prick testing with a panel
      of aeroallergens and a microarray-based panel of allergens (ISAC((r)); Phadia,
      Sweden) was performed in all patients. Prior to learning the results of molecular
      diagnosis, three of the authors reached a consensus on the indication of SIT and
      use of allergens following EAACI recommendations, basing their judgment on
      clinical history and skin prick test results before and after obtaining the ISAC
      results. The agreement coefficient (kappa index) was used to analyze the results.
      RESULTS: Fifty-nine percent of the patients were women with a mean age of 31 +/-
      13.63. Agreement in SIT indication before and after ISAC((r)) results was found
      in only 62 (46%) patients (kappa = 0.1057 +/- 0.0413). Concerning allergens used
      in the most common prescriptions before and after MD results, we obtained the
      following results: kappa = 0.117 +/- 0.0825 for grass; kappa = 0.1624 +/- 0.0639
      for olive; kappa = 0.0505 +/- 0.0548 for olive and grass; kappa = 0.1711 +/-
      0.0471 for grass and cypress; kappa = 0.1897 +/- 0.0493 for grass and London
      plane; kappa = 1 +/- 0.0842 for olive and cypress, and kappa = 0.3586 +/- 0.0798
      for other combinations. CONCLUSIONS: There was very low agreement concerning
      indication and use of allergens for SIT before and after performing MD. This
      discrepancy emphasizes the usefulness of MD, at least in areas of complex
      sensitization to pollen, in determining correct indication of SIT.

PMID- 22379959
TI  - Distance measurements on a dual-labeled TOAC AChR M2delta peptide in mechanically
      aligned DMPC bilayers via dipolar broadening CW-EPR spectroscopy.
AB  - A membrane alignment technique has been used to measure the distance between two
      TOAC nitroxide spin labels on the membrane-spanning M2delta, peptide of the
      nicotinic acetylcholine receptor (AChR), via CW-EPR spectroscopy. The TOAC
      labeled M2delta peptides were mechanically aligned using DMPC lipids on a planar
      quartz support, and CW-EPR spectra were recorded at specific orientations. Global
      analysis in combination with rigorous spectral simulation was used to
      simultaneously analyze data from two different sample orientations for both
      single- and double-labeled peptides. We measured an internitroxide distance of
      14.6 A from a   dual TOAC-labeled AChR M2delta peptide at positions 7 and 13 that
      closely matches with the 14.5 A distance obtained from a model of the labeled
      AChR M2delta peptide. In addition, the angles determining the relative
      orientation of the two nitroxides have been determined, and the results compare
      favorably with molecular modeling. The global analysis of the data from the
      aligned samples gives much more precise estimates of the parameters defining the
      geometry of the two labels than can be obtained from a randomly dispersed sample.

PMID- 22379961
TI  - Lentiviral vectors for cutaneous RNA managing.
AB  - Post-transcriptional managing of RNA plays a key role in the intricate network of
      cellular pathways that regulate our genes. Numerous small RNA species have
      emerged as crucial regulators of RNA processing and translation. Among these,
      microRNAs (miRNAs) regulate protein synthesis through specific interactions with
      target RNAs and are believed to play a role in almost any cellular process and
      tissue. Skin is no exception, and miRNAs are intensively studied for their role
      in skin homoeostasis and as potential triggers of disease. For use in skin and
      many other tissues, therapeutic RNA managing by small RNA technologies is now
      widely explored. Despite the easy accessibility of skin, the natural barrier
      properties of skin have challenged genetic intervention studies, and unique tools
      for studying gene expression and the regulatory role of small RNAs, including
      miRNAs, in human skin are urgently needed. Human immunodeficiency virus (HIV)
      derived lentiviral vectors (LVs) have been established as prominent carriers of
      foreign genetic cargo. In this review, we describe the use of HIV-derived LVs for
      efficient gene transfer to skin and establishment of long-term transgene
      expression in xenotransplanted skin. We outline the status of engineered LVs for
      delivery of small RNAs and their in vivo applicability for expression of genes
      and small RNA effectors including small hairpin RNAs, miRNAs and miRNA
      inhibitors. Current findings suggest that LVs may become key tools in
      experimental dermatology with particular significance for cutaneous RNA managing
      and in vivo genetic intervention.

PMID- 22379962
TI  - Tight junctions and differentiation--a chicken or the egg question?
AB  - Skin barrier function is indispensable to prevent the uncontrolled loss of water
      and solutes and to protect the body from external assaults. To fulfil this
      function, keratinocytes undergo a complex pathway of differentiation that
      terminates in the formation of the stratum corneum. Additionally, tight junctions
      (TJs), which are cell-cell junctions localized in the stratum granulosum, are
      involved in the barrier function of the skin. Important biological and clinical
      roles of TJs are strongly suggested by altered TJ protein levels and distribution
      in skin diseases like psoriasis, ichthyosis and atopic dermatitis. Because these
      skin diseases show alterations in differentiation and TJs, it was suggested that
      changes in TJs might simply be a consequence of altered differentiation. However,
      in this viewpoint, we like to argue that the situation is not as simple and
      depends on the specific microenvironment. We discuss three hypotheses regarding
      the interplay between TJs/TJ proteins and differentiation: (1) TJs/TJ proteins
      are influenced by differentiation, (2) differentiation is influenced by TJs/TJ
      proteins, and (3) TJs/TJ proteins and differentiation are independent of each
      other. In addition, the concept is introduced that both processes are going on at
      the same time, which means that while one specific TJ protein/barrier component
      might be influenced by differentiation, the other may influence differentiation.

PMID- 22379963
TI  - Is mechanical stress an important pathogenic factor in hidradenitis suppurativa?
AB  - Hidradenitis suppurativa (HS) is a chronic of recurrent, inflammatory, follicular
      disease that usually presents after puberty with painful deep-seated, inflamed
      lesions in the inverse skin areas of the body. It has been hypothesized that
      mechanical pressure or friction is a risk factor for HS. We describe the case of
      a man with a lower leg amputation who presented HS-like lesions on his leg stump
      after wearing a leg prosthesis. Although pilonidal sinus-like disease could not
      be excluded, we diagnosed him with HS-like lesions, induced by prosthesis-related
      friction. We argue that this case supports the concept that mechanical friction
      and a warm humid microclimate by occlusion contribute to HS development.

PMID- 22379964
TI  - Characterization of neurons from adult human skin-derived precursors in serum
      free medium : a PCR array and immunocytological analysis.
AB  - Adult stem cells could be small sources of neurons or other cellular types for
      regenerative medicine and tissue engineering. Recently, pluripotent stem cells
      have been extracted from skin tissue, which opened a new accessible source for
      research. To routinely obtain a high yield of functional neurons from adult human
      skin stem cells with defined serum-free medium, stem cells from abdominal skin
      were cultured in serum-free medium. To differentiate them, we used a defined
      medium containing growth factors. Differentiated cells were identified using the
      following methods: (i) Oil-red-O staining for adipocytes, immunocytochemistry
      with antibodies recognising (ii) neurofilaments and PGP9.5 for neural
      differentiation, (iii) glial fibrillary acidic protein (GFAP) for glial
      differentiation, (iv) Ki-67 for proliferative cells, (v) FM1-43 staining to
      analyse vesicle trafficking in neuronal cells and (vi) a PCR array was used. Stem
      cells were floating in spheres and were maintained in culture for 4 months or
      more. They expressed nestin and Oct 4 and were proliferative. We induced specific
      differentiation into adipocytes, glial and neuronal cells. The yields of
      differentiated neurons were high and reproducible. They were maintained for long
      time (1 month) in the culture medium. Furthermore, these neurons incorporated FM1
      43 dye, which indicates a potent acquisition of synaptic features in neurons.
      Stem cells from adult human skin could be valuable and reproducible tools/source
      to obtain high numbers of functional specific cellular types, such as neurons,
      for tissue engineering. In this work, the possibility to obtain a high yield of
      differentiated neurons, with the ability of endocytosis and vesicle cell
      trafficking, was shown.

PMID- 22379965
TI  - Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on
      pruritogen-induced scratching behavior.
AB  - Itch accompanies various skin diseases. As a number of mediators other than
      histamine can be involved in the itch sensation, H1 receptor antagonists are not
      necessarily effective in treating itch. External application of antipruritic
      drugs is occasionally used as an alternative therapy for pruritic skin
      conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so,
      the actual effects of these drugs on the itch sensation have yet to be studied in
      detail. To verify the antipruritic effects of crotamiton, capsaicin, and a
      corticosteroid on the itch sensation, we examined the inhibitory effects of these
      drugs on various pruritogen-induced scratching behaviors in mice. Topical
      application of 10% crotamiton moderately inhibited histamine-, serotonin-, and
      PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also
      exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2
      agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol
      propionate) remarkably inhibited the scratching behaviors induced by all of the
      pruritogenic agents tested. Therapeutic effects of capsaicin on substance P
      induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+)
      C fibers and/or by altered responsiveness of the mast cells. In addition, the
      antipruritic effects of crotamiton and corticosteroid appear to be, at least
      partly, associated with a TRPV1-independent pathway. This study examined the itch
      responses to pruritogens and demonstrated the mode of action of the externally
      applied antipruritic drugs.

PMID- 22379966
TI  - Proteomic analysis identifies new biomarkers for postmenopausal and dry skin.
AB  - A proteomic analysis of stratum corneum (SC) samples of normal healthy skin
      revealed the presence of more than 70 proteins by 2D electrophoresis. The
      majority of these proteins to our knowledge have not yet been described in normal
      SC. We analysed by Western blot the levels of 25 proteins in the SC taken from
      postmenopausal and dry skin compared with young and normal skin, respectively. In
      postmenopausal skin, there was a significantly increased amount of heat shock
      protein 27, plakoglobin and desmoglein 1, whereas transglutaminase 3,
      apolipoprotein D and acid ceramidase levels were significantly reduced compared
      with the SC of young skin. We confirmed corneodesmosin as a marker of dry skin.
      In addition, we showed for the first time that the levels of both
      phosphatidylethanolamine-binding protein 1 and annexin A2 were significantly
      increased in the SC of dry skin compared with the SC of normal skin. These
      results suggest that a proteomic analysis of the SC obtained using a non-invasive
      varnish stripping method is an attractive alternative to invasive methods to
      better characterize changes in the physiology of ageing and dry skin.

PMID- 22379967
TI  - 5,7-Dimethoxyflavone, an activator of PPARalpha/gamma, inhibits UVB-induced MMP
      expression in human skin fibroblast cells.
AB  - Peroxisome proliferator-activated receptors (PPARs), which are members of the
      nuclear hormone receptor superfamily, are a family of ligand-activated
      transcription factors that consist of three isotypes (PPAR alpha, delta and
      gamma). PPAR activity was previously thought to be limited to lipid metabolism
      and glucose homeostasis; however, intensive studies of PPARalpha/gamma in recent
      years have revealed their importance in age-related inflammation and photoaging
      as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor
      kappa B (NF-kappaB). We evaluated the ability of the PPARalpha/gamma activator
      5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP
      expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF
      and then exposed to UVB irradiation. MMP expression, production and activity were
      determined by reverse transcription-polymerase chain reaction, enzyme-linked
      immunosorbent assay and gelatin zymography. PPARalpha/gamma expression, catalase
      expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP
      1) and NF-kappaB signalling were evaluated by Western blot analysis.
      PPARalpha/gamma activity was assessed with the GAL4/PPARalpha/gamma
      transactivation assay. We found that 5,7-DMF strongly decreased MMP expression,
      production and activity. In addition, 5,7-DMF significantly increased
      PPARalpha/gamma activation and catalase expression, thereby downregulating UVB
      induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and
      downstream transcription factors. Finally, 5,7-DMF reduced IkappaBalpha
      phosphorylation, blocked NF-kappaB p65 nuclear translocation, strongly suppressed
      proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents
      UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age
      related inflammation via NF-kappaB and MAPK/AP-1 pathways. Our findings suggest
      the usefulness of 5,7-DMF for preventing and treating skin photoaging.

PMID- 22379968
TI  - SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced
      skin carcinogenesis studies.
AB  - Strains of mice vary in their susceptibility to ultra-violet (UV) radiation
      induced skin tumors. Some strains of hairless mice (homozygous for the
      spontaneous Hr(hr)  mutation) are particularly susceptible to these tumors. The
      skin tumors that develop in hairless mice resemble, both at the morphologic and
      molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors
      in human. The most commonly employed hairless mice belong to the SKH1 stock.
      However, these mice are outbred and their genetic background is not
      characterized, which makes them a poor model for genetic studies. We have
      developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd
      (now at generation F31). In order to characterize the genetic background of this
      new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140
      single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse
      genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that
      they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice.
      In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice
      are suitable for transgenic production by classical pronuclear microinjection.
      This new inbred strain will be useful for the development of transgenic and
      congenic strains on a hairless inbred background as well as the establishment of
      syngeneic tumor cell lines. These new tools can potentially help elucidate a
      number of features of the cutaneous response to UV irradiation in humans,
      including the effect of genetic background and modifier genes.

PMID- 22379969
TI  - Cost-effective HLA-Cw06:02 typing in a Caucasian population.
AB  - Considering the clinical and genetic heterogeneity of psoriasis which may
      translate into distinct disease pathology and treatment response, correct typing
      of the main candidate gene HLA-C is critical but not trivial. To facilitate
      genotyping, we compared established techniques with our newly developed tool.
      Here, we propose that typing of four single nucleotide polymorphic markers within
      the HLA-C region correctly determines HLA-Cw*06:02 genotypes in psoriatic cases
      and healthy controls in a population of Caucasian origin. Typing of the SNPs
      presented herein proved to be precise, reliable, time and cost effective, and
      requiring low amount of DNA.

PMID- 22379970
TI  - Calcitonin gene-related peptide (CGRP) may award relative protection from
      interferon-gamma-induced collapse of human hair follicle immune privilege.
AB  - Interferon-gamma (IFNgamma)-induced collapse of hair follicle (HF) immune
      privilege (IP) is a key element in the pathogenesis of alopecia areata. In this
      pilot study, we investigated whether the immunosuppressive neuropeptide,
      calcitonin gene-related peptide (CGRP), can protect from and/or restore IFNgamma
      induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor
      like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence
      of IFNgamma, with CGRP added before or after. Adding CGRP after IFNgamma
      administration ('restoration assay') failed to downregulate IFNgamma-induced
      ectopic MHC class I expression, while MHC class II expression was reduced.
      However, administering CGRP before IFNgamma application ('protection assay')
      significantly reduced the IFNgamma-induced overexpression and ectopic expression
      of MHC class I and II and reduced the increased degranulation of perifollicular
      mast cells induced by IFNgamma. This suggests that CGRP may not restore HF-IP
      once it has collapsed, but may protect it from collapsing. Therefore, CRLR
      stimulation might help to retard AA progression.

PMID- 22379971
TI  - Cutaneous iontophoretic delivery of CGP69669A, a sialyl Lewis(x)  mimetic, in
      vitro.
AB  - The aim was to investigate the feasibility of using iontophoresis for the
      cutaneous delivery of the E-selectin antagonist CGP69669A, a sialyl Lewis(x) 
      glycomimetic with potential activity against inflammatory skin diseases. The
      effects of current density and formulation on iontophoretic transport were
      evaluated in porcine and human skin in vitro. Cumulative permeation of CGP69669A
      increased with current density (69.73+/-9.51, 113.97+/-26.80 and 160.44+/
      13.79MUg/cm(2) at 0.1, 0.3 and 0.5mA/cm(2) , respectively) and drug concentration
      (37.42+/-13.13, 78.96+/-23.13 and 160.44+/-13.79MUg/cm(2) , at 1, 3 and 5mg/ml,
      respectively). In contrast, passive delivery was negligible. Although permeation
      from a 2% hydroxyethyl cellulose gel was lower than that from aqueous solution,
      skin deposition - more relevant for the local treatment of dermatological
      conditions - was 3-fold higher. The results demonstrated that although CGP69669A
      cannot be delivered passively into the skin it is an excellent candidate for
      transdermal iontophoresis, a technique that is ideally suited to the delivery of
      glycomimetics.

PMID- 22379972
TI  - 8-Methoxypsoralen plus UVA treatment increases the proportion of CLA+ CD25+ CD4+
      T cells in lymph nodes of K5.hTGFbeta1 transgenic mice.
AB  - 8-Methoxypsoralen plus UVA (PUVA) photochemotherapy is an effective treatment for
      many skin diseases including psoriasis. However, its exact mechanism of
      therapeutic action is incompletely understood. Previously, in K5.hTGFbeta1
      transgenic psoriatic mice, we found that PUVA induces Foxp3+ CD25+ CD4+
      regulatory T cells in both lymph node and spleen. Now, in the same model, we
      investigated whether cutaneous lymphocyte-associated antigen (CLA) mediates
      PUVA's effect on homing of CD25+ CD4+  T cells to the lymph nodes of K5.hTGFbeta1
      transgenic mice. We found that a low dose of topical PUVA maximally increased the
      proportion of CLA + CD25+ CD4 + T cells in the lymph nodes by up to 8-fold. We
      also observed an increased number of Foxp3+ CD25+  T cells in the skin of the
      mice after PUVA treatment. Together, these findings suggest that PUVA affects the
      homing of regulatory T cells.

PMID- 22379973
TI  - Sirtuin 4 identification in normal human epidermal keratinocytes and its relation
      to sirtuin 3 and energy metabolism under normal conditions and UVB-induced
      stress.
AB  - Sirtuins (SIRT) are NAD(+) -dependent deacetylases and ADP-ribosyltransferases
      that play a critical role in metabolism and epigenetics. SIRT3 and SIRT4 are of
      particular interest because they are localized in the mitochondria where energy
      is generated and their expression is inversely proportional to each other. Here,
      we report data, for the first time, demonstrating the presence of SIRT4 in normal
      human epidermal keratinocytes (NHEK) and confirm that its expression is inversely
      related to SIRT3 in these cells and that they follow a temporal cycle. Further,
      UVB radiation modified their expression, as well as ATP and H2 O2 levels. These
      deviations from the normal sirtuin cycles after UVB exposure can be an epigenetic
      indicator of lower metabolism levels.

PMID- 22379974
TI  - Influence of the application area on finite dose permeation in relation to drug
      type applied.
AB  - For finite dose skin absorption experiments, a homogeneous donor distribution
      over the skin surface is usually assumed. However, the influence of the surface
      distribution on skin absorption is still unknown. The aim of this study was to
      evaluate the influence of the application area on the permeation of drugs during
      finite dose skin absorption experiments in static Franz diffusion cells.
      Permeation experiments with stained aqueous drug formulations were conducted, and
      the application area was determined by a suitable, objective, automated
      computational approach. The permeation of caffeine is strongly dependent on the
      application area. The variability between single experiments decreased when
      including the application area. For the lipophilic flufenamic acid, this was not
      the case. The variability highly increased after inclusion of the application
      area. Thus, a correction of the area is misleading. In summary, depending on the
      drug's physicochemical characteristics, the application area may influence skin
      absorption.

PMID- 22379975
TI  - First symposium on natural gene therapy of the skin.

PMID- 22379976
TI  - Expression of concern.

PMID- 22379978
TI  - Autonomic dysfunction in patients with advanced cancer; prevalence, clinical
      correlates and challenges in assessment.
AB  - BACKGROUND: The results of a small number of studies of autonomic function in
      patients with advanced cancer suggest that autonomic dysfunction (AD) is common.
      In other disease-specific groups this is associated with decreased survival,
      falls and symptoms such as postural hypotension, nausea, early satiety and
      fatigue. The contribution of AD to symptoms in advanced cancer is unknown.
      METHODS: We conducted a prospective cohort study designed to identify the risk
      factors for falls in patients with advanced cancer. Ambulant adult patients
      admitted consecutively to palliative care services were invited to participate.
      Participants underwent an assessment at baseline which included standard clinical
      tests of autonomic function, assessment of symptom severity, muscle strength,
      anthropometric measurements, walking speed, medication use, comorbidities and
      demographics. Information regarding survival was recorded ten months following
      cessation of recruitment. The clinical correlates of AD, defined as definite or
      severe dysfunction using Ewing's classification, were examined by univariate and
      multivariate logistic regression analysis. Survival analysis was conducted using
      Kaplan-Meier plots and the log rank test. RESULTS: Of 185 patients recruited, 45%
      were unable to complete all of the clinical tests of autonomic function. Non
      completion was associated with scoring high on clinical indicators of frailty. It
      was possible to accurately classify 138/185 (74.6%) of participants as having
      either definite or severe versus normal, early or atypical AD: 110 (80%) had
      definite/severe AD. In logistic regression analysis, age (OR = 1.07 [95% CI; 1.03
      1.1] P = 0.001) and increased severity of fatigue (OR = 1.26 [95% CI; 1.05-1.5] p
      = 0.016) were associated with having definite/severe AD. In analysis adjusted for
      age, median survival of participants with definite/severe AD was shorter than in
      those with normal/early/atypical classification (chi2 = 4.3, p = 0.038).
      CONCLUSIONS: Autonomic dysfunction is highly prevalent in patients with advanced
      cancer and is associated with increased severity of fatigue and reduced survival.
      Due to frailty, up to 45% of participants were unable to complete standard
      clinical tests of autonomic function. In order to further investigate the impact
      of AD and the therapeutic potential of treatment of AD in patients with advanced
      cancer, the validity of alternative novel methods of assessing autonomic function
      must be appraised.

PMID- 22379979
TI  - Cellulose utilization in forest litter and soil: identification of bacterial and
      fungal decomposers.
AB  - Organic matter decomposition in the globally widespread coniferous forests has an
      important role in the carbon cycle, and cellulose decomposition is especially
      important in this respect because cellulose is the most abundant polysaccharide
      in plant litter. Cellulose decomposition was 10 times faster in the fungi
      dominated litter of Picea abies forest than in the bacteria-dominated soil. In
      the soil, the added (13)C-labelled cellulose was the main source of microbial
      respiration and was preferentially accumulated in the fungal biomass and
      cellulose induced fungal proliferation. In contrast, in the litter, bacterial
      biomass showed higher labelling after (13)C-cellulose addition and bacterial
      biomass increased. While 80% of the total community was represented by 104-106
      bacterial and 33-59 fungal operational taxonomic units (OTUs), 80% of the
      cellulolytic communities of bacteria and fungi were only composed of 8-18 highly
      abundant OTUs. Both the total and (13)C-labelled communities differed
      substantially between the litter and soil. Cellulolytic bacteria in the acidic
      topsoil included Betaproteobacteria, Bacteroidetes and Acidobacteria, whereas
      these typically found in neutral soils were absent. Most fungal cellulose
      decomposers belonged to Ascomycota; cellulolytic Basidiomycota were mainly
      represented by the yeasts Trichosporon and Cryptococcus. Several bacteria and
      fungi demonstrated here to derive their carbon from cellulose were previously not
      recognized as cellulolytic.

PMID- 22379980
TI  - Influences of establishment and maintenance of territory on reproductive activity
      in the male dwarf gourami Colisa lalia.
AB  - We examined the importance of establishment and maintenance of territory on
      reproductive activity in the male dwarf gourami, Colisa lalia. After three males
      had been forced to fight for territory (five sets) for three weeks, social status
      was divided into three classes: the territorially dominant male, which guarded
      the territory under the floating nest; the second male which remained near the
      nest and occasionally attacked the dominant male; and the third male which was
      non-aggressive and remained at a distance from the other two males. Comparing
      testicular size by gonadosomatic indices (GSI) after three weeks of aggression,
      GSI of the dominant male (1.19 +/- 0.07) was significantly larger than that of
      the second (0.81 +/- 0.15) and the third (0.62 +/- 0.08) males, as well as the
      initial control (not involved in any experiments: 0.85 +/- 0.10, n = 5),
      indicating that the testes of the dominant males enlarge during territory
      defense. Histological observations of testes revealed that sperm production in
      the dominant males was more active compared to males of other classes, although
      spermatogenesis was confirmed in all males examined, suggesting that dominance
      accelerates sperm production. Social-status dependent development of testes
      suggests an absence of sperm competition due to the lack of sneaking by
      subordinate males. Since non-territorial males do not engage in alternative
      tactics (e.g., sneaking) leading to emission of semen, male C. lalia must obtain
      and defend territory if they are to increase their reproductive success.

PMID- 22379981
TI  - Costs of parturition and rearing in female sika deer (Cervus nippon).
AB  - The costs of parturition and lactation of female sika deer on Kinkazan Island
      (9.6 km(2) in size), northern Japan, which live at a high density (about 50
      deer/km(2)), were evaluated by comparison of body weights of 481 females measured
      during a 15 year study (1993-2008). Weight data were chosen from only females
      that did not give birth in the preceding year. The mean body weight of females
      that did not give birth ("yelds") was significantly lower (P < 0.001) than that
      of females who gave birth ("milks"); yelds' body weight was 93.1% and 83.5% that
      of milks in the preceding and parturition years, respectively. The yelds
      increased in body weight by the following March by 8.2% (P < 0.001), whereas
      milks did not. Among the milks, those whose fawns survived until the following
      May ("rearing milks") lost body weight by 14.9% (P < 0.001). Milks who lost fawns
      within a week after birth ("early fawn-less milks") did not lose body weight (P =
      0.583), while those whose fawns died after the first autumn but died before May
      ("late fawn-less milks") lost body weight by 19.9% (P < 0.001). These results
      indicate that sika deer females do not enter estrus unless they are heavy enough,
      and that both parturition and rearing are costly for sika deer mothers living in
      high-density conditions.

PMID- 22379982
TI  - Comparative molecular phylogeny and evolution of sex chromosome DNA sequences in
      the family Canidae (Mammalia: Carnivora).
AB  - To investigate the molecular phylogeny and evolution of the family Canidae,
      nucleotide sequences of the zinc-finger-protein gene on the Y chromosome (ZFY,
      924-1146 bp) and its homologous gene on the X chromosome (ZFX, 834-839 bp) for
      twelve canid species were determined. The phylogenetic relationships among
      species reconstructed by the paternal ZFY sequences closely agreed with those by
      mtDNA and autosomal DNA trees in previous reports, and strongly supported the
      phylogenetic affinity between the wolf-like canids clade and the South American
      canids clade. However, the branching order of some species differed between
      phylogenies of ZFY and ZFX genes: Cuon alpinus and Canis mesomelas were included
      in the wolf-like canid clades in the ZFY tree, whereas both species were
      clustered in a group of Chrysocyon brachyurus and Speothos venaticus in the ZFX
      tree. The topology difference between ZFY and ZFX trees may have resulted from
      the two-times higher substitution rate of the former than the latter, which was
      clarified in the present study. In addition, two types of transposable element
      sequence (SINE-I and SINE-II) were found to occur in the ZFY final intron of the
      twelve canid species examined. Because the SINE-I sequences were shared by all
      the species, they may have been inserted into the ZFY of the common ancestor
      before species radiation in Canidae. By contract, SINE-II found in only Canis
      aureus could have been inserted into ZFY independently after the speciation. The
      molecular diversity of SINE sequences of Canidae reflects evolutionary history of
      the species radiation.

PMID- 22379983
TI  - Cryptic anuran biodiversity in Bangladesh revealed by mitochondrial 16S rRNA gene
      sequences.
AB  - To survey the diversity of anuran species in Bangladesh, we compared
      mitochondrial 16S rRNA gene sequences (approximately 1.4 kbp) from 107 Bangladesh
      frog specimens. The results of genetic divergence and phylogenetic analyses
      incorporating data from related species revealed the occurrence of at least eight
      cryptic species. Hoplobatrachus tigerinus from two districts diverged
      considerably, indicating the involvement of a cryptic species. Two Fejervarya sp.
      (large and medium types) and Hylarana cf. taipehensis formed lineages distinct
      from related species and are probably new species. Microhyla cf. ornata differed
      from M. ornata with respect to type locality area and involved two distinct
      species. In addition, we found that Hylarana sp. and Microhyla sp. did not match
      congeners examined to date in either morphology or 16S rRNA sequence. The
      occurrence of M. fissipes was tentatively suggested. Consequently, at least, 19
      species were found from Bangladesh in this study. These findings revealed a rich
      anuran biodiversity in Bangladesh, which is unexpected considering the rather
      simple topographic features of the country.

PMID- 22379984
TI  - Symbiodinium clade C dominates zooxanthellate corals (Scleractinia) in the
      temperate region of Japan.
AB  - Endosymbiotic algae of the genus Symbiodinium have been divided into nine clades
      (A-I) following genetic classification; some clades are known to have
      physiological properties that enable the coral hosts to adapt to different
      environmental conditions. To understand the relationships of coral-alga
      symbioses, we focused on Symbiodinium diversity in zooxanthellate corals living
      under the severe environmental conditions of the temperate region (30 degrees -35
      degrees N) of Japan. We investigated Symbiodinium clades in 346 colonies
      belonging to 58 coral species from six locations. We then selected three coral
      species-Acropora hyacinthus, Acropora japonica, and Cyphastrea chalcidicum-to
      investigate whether Symbiodinium clades changed during winter or summer over the
      course of year (May 2009-Apr 2010) in Tanabe Bay, Japan. Three Symbiodinium
      clades (C, D, and F) were detected in corals in the temperate region. Notably, 56
      coral species contained Symbiodinium clade C. Oulastrea crispata predominantly
      contained clade D, but traces of clade C were also detected in all samples. The
      temperate-specific species Alveopora japonica contained clades C and F
      simultaneously. Seasonal change of symbiont clades did not occur in the three
      coral species during the investigation period where SSTs range on 12.5-29.2
      degrees C. However, we found Acropora (2 spp.) and Cyphastrea (1 sp.) contained
      different subcladal types of clade C. These results reveal that most coral
      species harbored Symbiodinium clade C stably throughout the year, suggesting that
      Symbiodinium clade C shows low-temperature tolerance, and that two hypothetical
      possibilities; genetic differences of subcladal types generating physiological
      differences or wide physiological flexibility in the clade C.

PMID- 22379985
TI  - Changes in thyroid hormone levels during zebrafish development.
AB  - The zebrafish (Danio rerio) has been used as a model for the study of endocrine
      disrupting chemicals. This study set out to determine the profiles of whole-body
      thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels during the development of
      zebrafish from embryo to adult. Enzyme-linked immunoassay was used to analyze
      whole-body T4 and T3 contents. The results showed that whole-body T4 and T3
      levels remained stable during the pre-hatching period (0-3 d) and increased
      significantly during early development after hatching. The T3 level peaked at
      0.28 +/- 0.01 ng g(-1) body weight at 10 days post-fertilization (dpf), and T4
      peaked at 0.58 +/- 0.09 ng g(-1) body weight at 21 dpf. Both thyroid hormones
      subsequently declined during later development. This study establishes a baseline
      for thyroid hormones in zebrafish, which will be vital for the understanding of
      thyroid hormone functions and in future studies of thyroid toxicants in this
      species.

PMID- 22379986
TI  - Structure and hibernation-associated expression of the transient receptor
      potential vanilloid 4 channel (TRPV4) mRNA in the Japanese grass lizard
      (Takydromus tachydromoides).
AB  - Animals possess systems for sensing environmental temperature using temperature
      sensitive ion channels called transient receptor potential channels (TRPs).
      Various TRPs have been identified and characterized in mammals. However, those of
      ectotherms, such as reptiles, are less well studied. Here, we identify the V
      subfamily of TRP (TRPV) in two reptile species: Japanese grass lizard (Takydromus
      tachydromoides) and Japanese four-lined ratsnake (Elaphe quadrivirgata).
      Phylogenetic analysis of TRPVs indicated that ectothermic reptilian TRPVs are
      more similar to those of endothermic chicken and mammals, than to other
      ectotherms, such as frog and fish. Expression analysis of TRPV4 mRNA in the
      lizard showed that its expression in tissues and organs is specifically
      controlled in cold environments and hibernation. The mRNA was ubiquitously
      expressed in seven tissues/organs examined. Both cold-treatment and hibernation
      lowered TRPV4 expression, but in a tissue/organ-specific manner. Cold-treatment
      reduced TRPV4 expression in tongue and muscle, while in hibernation it was
      reduced more widely in brain, tongue, heart, lung, and muscle. Interestingly,
      however, levels of TRPV4 mRNA in the skin remained unaffected after entering
      hibernation and cold-treatment, implying that TRPV4 in the skin may act as an
      environmental temperature sensor throughout the reptilian life cycle, including
      hibernation. This is the first report, to our knowledge, to describe reptilian
      TRPV4 in relation to hibernation.

PMID- 22379987
TI  - Collagen reconstitution is inversely correlated with induction of limb
      regeneration in Ambystoma mexicanum.
AB  - Amphibians can regenerate missing body parts, including limbs. The regulation of
      collagen has been considered to be important in limb regeneration. Collagen
      deposition is suppressed during limb regeneration, so we investigated collagen
      deposition and apical epithelial cap (AEC) formation during axolotl limb
      regeneration. The accessory limb model (ALM) has been developed as an alternative
      model for studying limb regeneration. Using this model, we investigated the
      relationship between nerves, epidermis, and collagen deposition. We found that Sp
      9, an AEC marker gene, was upregulated by direct interaction between nerves and
      epidermis. However, collagen deposition hindered this interaction, and resulted
      in the failure of limb regeneration. During wound healing, an increase in
      deposition of collagen caused a decrease in the blastema induction rate in ALM.
      Wound healing and limb regeneration are alternate processes.

PMID- 22379988
TI  - Sexual size dimorphism and allometric growth of Morelet's crocodiles in
      captivity.
AB  - Few studies have conducted morphological analyses of crocodilians, and little
      information exists on differences between size-classes and sexes in Neotropical
      crocodilians. In this study, we measured nine morphological traits in 121 captive
      Morelet's crocodiles Crocodylus moreletii (81 females and 40 males). Our results
      revealed that individuals < 2 m total length do not exhibit sexual dimorphism in
      morphometric characteristics. However, for crocodiles over 2 m in length, males
      were significantly larger than females in terms of dorsal-cranial length, cranial
      width, snout width and snout-ventral length. In general, morphological traits
      demonstrated a strongly significant relationship with total length at the smaller
      size class of 150-200 cm length. However, in the highest size class of 250-300 cm
      length (large adult males), morphological traits were no longer significantly
      related with total length. Male crocodiles demonstrated allometric growth of
      cranial morphology with significantly greater increase in cranial width, snout
      width, and mid-snout width relative to total length at higher size classes.
      Morphological dimorphism and allometric growth may be associated with adaptive
      strategies for reproductive success.

PMID- 22379989
TI  - Molecular characterization and gene expression of Japanese eel (Anguilla
      japonica) gonadotropin receptors.
AB  - A luteinizing hormone receptor (lhr) cDNA with high identity to other fish lhrs
      was fully cloned from the ovary of the Japanese eel (Anguilla japonica). The
      genes for two gonadotropin receptors (Gthr), follicle-stimulating hormone
      receptor (fshr) and lhr, were differentially expressed during oogenesis, which
      was artificially induced by salmon pituitary extract, a gonadotropin-rich source.
      Transcript abundance of fshr was significantly elevated at the early vitellogenic
      stage and peaked at the late vitellogenic stage, while lhr gene expression
      rapidly induced at the late vitellogenic stage and thereafter remained at a high
      level. The abundance of fshr and lhr transcripts was highest in the ovary in
      female eels. In addition to the ovary, forebrain was a major site for the fshr
      transcript, although the level did not change with reproductive status.
      Furthermore, it was examined how eel Gthrs were activated by two mammalian
      chrionic gonadtropin (CG), equine CG (eCG) and human CG (hCG), that have been
      used for study of fish reproduction as substitutes for homologous Gths. Both CGs
      specifically activated eel Lhr, but not Fshr, although the degree of
      effectiveness was different; thus the concentration of hCG (0.1 ng/ml) required
      for significant activation of Lhr was much lower than that of eCG (100 ng/ml).
      These data on gene expression and ligand-activation of Gthrs suggest that Fsh and
      Lh act differentially in the regulation of reproductive function in Japanese eel.

PMID- 22379990
TI  - Insight from genome-wide association studies into coronary heart disease.

PMID- 22379991
TI  - Attention deficit hyperactivity disorder pharmacogenetics: the dopamine
      transporter and D4 receptor.

PMID- 22379992
TI  - The challenges of developing a 'medical-grade' genome.

PMID- 22379994
TI  - The challenges of methotrexate pharmacogenetics in rheumatoid arthritis.

PMID- 22379995
TI  - GeneNews Limited: bringing the blood transcriptome to personalized medicine.
AB  - GeneNews Limited (TSX:GEN) is a molecular diagnostics company, uniquely
      positioned to deliver on the promise of personalized medicine. GeneNews has
      developed and patented the Sentinel Principle((r)), an innovative approach to
      identify clinically actionable disease biomarkers from the blood transcriptome.
      Novel biomarker panels have been identified to address unmet clinical needs in a
      broad spectrum of malignancy, including those for oncology, cardiovascular,
      metabolic and neurological related disorders. Currently available products and
      services from GeneNews are: ColonSentryTM, the world's first blood-based
      molecular test for colorectal cancer, and; the SentinelGXTM Pharmacogenomic and
      Companion Diagnostic BloodRNATM services, established to effectively support
      pharmaceutical partners in their companion diagnostic, development efforts.

PMID- 22379996
TI  - Institutional Profile: Golden Helix Institute of Biomedical Research:
      interdisciplinary research and educational activities in pharmacogenomics and
      personalized medicine.
AB  - The Golden Helix Institute of Biomedical Research is an international nonprofit
      scientific organization with interdisciplinary research and educational
      activities in the field of genome medicine in Europe, Asia and Latin America.
      These activities are supervised by an international scientific advisory council,
      consisting of world leaders in the field of genomics and translational medicine.
      Research activities include the regional coordination of the Pharmacogenomics for
      Every Nation Initiative in Europe, in an effort to integrate pharmacogenomics in
      developing countries, the development of several national/ethnic genetic
      databases and related web services and the critical assessment of the impact of
      genetics and genomic medicine on society in various countries. Educational
      activities also include the organization of the Golden Helix Symposia((r)), which
      are high-profile scientific research symposia in the field of personalized
      medicine and the Golden Helix Pharmacogenomics Days, an international educational
      activity focused on pharmacogenomics, as part of its international
      pharmacogenomics education and outreach efforts.

PMID- 22379997
TI  - CDA deficiency as a possible culprit for life-threatening toxicities after
      cytarabine plus 6-mercaptopurine therapy: pharmacogenetic investigations.
AB  - We describe here the case of a 7-year old girl with lymphoma who developed life
      threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial
      investigations on canonical thiopurine methyltransferase genetic polymorphism
      proved to be negative. We focused next on deregulations affecting the CDA gene
      implicated in the liver disposition of cytarabine. This patient was homozygous
      for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter,
      two genotypes with reported opposite effects on CDA phenotype. To determine the
      CDA status of this patient, additional functional testing was performed and
      eventually demonstrated that this patient was a poor metabolizer. This case
      demonstrates that besides affecting thiopurine methyltransferase, dysregulations
      with CDA should be screened to anticipate toxicities with the cytarabine plus
      mercaptopurine combination.

PMID- 22379998
TI  - Genome-wide mapping for clinically relevant predictors of lamotrigine- and
      phenytoin-induced hypersensitivity reactions.
AB  - AIMS: An association between carbamazepine-induced hypersensitivity and HLA
      A*3101 has been reported in populations of both European and Asian descent. We
      aimed to investigate HLA-A*3101 and other common variants across the genome as
      markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine
      and phenytoin. MATERIALS & METHODS: We recruited patients with lamotrigine
      induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958
      British birth cohort was used as a control (n = 1296). HLA-A*3101 was imputed
      from genome-wide association study data. We applied genome-wide association to
      study lamotrigine- and phenytoin-induced cADR, and total cADR cases combined.
      RESULTS: Neither HLA-A*3101 nor any other genetic marker significantly predicted
      lamotrigine- or phenytoin-induced cADRs. CONCLUSION: HLA-A*3101 does not appear
      to be a predictor for lamotrigine- and phenytoin-induced cADRs in Europeans. Our
      genome-wide association study results do not support the existence of a
      clinically relevant common variant for the development of lamotrigine- or
      phenytoin-induced cADRs. As a predictive marker, HLA-A*3101 appears to be
      specific for carbamazepine-induced cADRs.

PMID- 22379999
TI  - Prediction of warfarin dose: why, when and how?
AB  - Prediction models are the key to individualized drug therapy. Warfarin is a
      typical example of where pharmacogenetics could help the individual patient by
      modeling the dose, based on clinical factors and genetic variation in CYP2C9 and
      VKORC1. Clinical studies aiming to show whether pharmacogenetic warfarin dose
      predictions are superior to conventional initiation of warfarin are now underway.
      This review provides a broad view over the field of warfarin pharmacogenetics
      from basic knowledge about the drug, how it is monitored, factors affecting dose
      requirement, prediction models in general and different types of prediction
      models for warfarin dosing.

PMID- 22380000
TI  - Pharmacogenetics of antidepressant drugs: current clinical practice and future
      directions.
AB  - While antidepressants are widely used to treat mood and anxiety disorders, only
      half of the patients will respond to antidepressant treatment and only one-third
      of patients experience a full remission of symptoms. The identification of
      genetic biomarkers that predict antidepressant-treatment response can improve
      current clinical practice. This is an emerging field known as pharmacogenetics,
      which comprises of genetic studies on both the pharmacokinetics and
      pharmacodynamics of treatment response. Recent studies on antidepressant
      treatment response have focused on both aspects of pharmacogenetics research,
      identifying new candidate genes that may predict better treatment response for
      patients. This paper reviews recent findings on the pharmacogenetics of
      antidepressant drugs and future clinical applications. Ultimately, these studies
      should lead to the use of genetic testing to guide the use of antidepressants in
      clinical practice.

PMID- 22380002
TI  - Regulation of gene expression in atherosclerosis: insights from microarray
      studies in monocytes/macrophages.
AB  - Atherosclerosis is a pathological phenomenon in which the walls of large arteries
      thicken and lose elasticity as a result of the growth of atheromatous lesions. It
      is a complex, multifactorial disease that involves several cell types and various
      pathobiological processes. Its genetic basis has not yet been deciphered, but it
      is related to complex multigene patterns influenced by environmental
      interactions. In this review, we focus specifically on the application of
      microarrays to atherosclerosis research using monocytes and monocyte-derived
      macrophages, as these are key cells in all phases of atherosclerosis, from the
      formation of foam cells to the destabilization and rupture of the atherosclerotic
      plaque. These studies have provided relevant information on genes involved in
      atherosclerosis development, contributing to our understanding of the molecular
      mechanisms that underlie this complex disease.

PMID- 22380001
TI  - Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a
      challenge for clinical implementation.
AB  - In the past decade, significant strides have been made in the area of
      cardiovascular pharmacogenomic research, with the discovery of associations
      between certain genotypes and drug-response phenotypes. While the motivations for
      personalized and predictive medicine are promising for patient care and support a
      model of health system efficiency, the implementation of pharmacogenomics for
      cardiovascular therapeutics on a population scale faces substantial challenges.
      The greatest obstacle to clinical implementation of cardiovascular
      pharmacogenetics may be the lack of both reproducibility and agreement about the
      validity and utility of the findings. In this review, we present the scientific
      evidence in the literature for diagnostic variants for the US FDA-labeled
      cardiovascular therapies, namely CYP2C19 and clopidogrel, CYP2C9/VKORC1 and
      warfarin, and CYP2D6/ADRB1 and beta-blockers. We also discuss the effect of
      HMGCR/LDLR in decreasing the effectiveness of low-density lipoprotein cholesterol
      with statin therapy, the SLCO1B1 genotype and simvastatin myotoxicity, and
      ADRB1/ADD1 for antihypertensive response.

PMID- 22380003
TI  - The relationship between hospital work environment and nurse outcomes in
      Guangdong, China: a nurse questionnaire survey.
AB  - AIMS AND OBJECTIVES: This study examines the relationship between hospital work
      environments and job satisfaction, job-related burnout and intention to leave
      among nurses in Guangdong province, China. BACKGROUND: The nursing shortage is an
      urgent global problem and also of concern in China. Studies in Western countries
      have shown that better work environments are associated with higher nurse
      satisfaction and lower burnout, thereby improving retention and lowering turnover
      rates. However, there is little research on the relationship between nurse work
      environments and nurse outcomes in China. DESIGN: This is a cross-sectional
      study. Survey data were collected from 1104 bedside nurses in 89 medical,
      surgical and intensive care units in 21 hospitals across the Guangdong province
      in China. METHODS: Stratified convenience sampling was used to select hospitals,
      and systematic sampling was used to select units. All staff nurses working on
      participating units were surveyed. The China Hospital Nurse Survey, including the
      Practice Environment Scale of the Nursing Work Index and Maslach Burnout
      Inventory, was employed to collect data from nurses. Statistical significance
      level was set at 0.05. RESULTS: Thirty-seven per cent of the nurses experienced
      high burnout, and 54% were dissatisfied with their jobs. Improving nurses' work
      environments from poor to better was associated with a 50% decrease in job
      dissatisfaction and a 33% decrease in job-related burnout among nurses.
      CONCLUSION: Burnout and job dissatisfaction are high among hospital nurses in
      Guangdong province, China. Better work environments for nurses were associated
      with decreased job dissatisfaction and job-related burnout, which may
      successfully address the nursing shortage in China. RELEVANCE TO CLINICAL
      PRACTICE: The findings of this study indicate that improving work environments is
      essential to deal with the nursing shortage; the findings provide motivation for
      nurse managers and policy makers to improve work environments of hospital nurses
      in China.

PMID- 22380004
TI  - In silico identification of novel lead compounds with AT1 receptor antagonist
      activity: successful application of chemical database screening protocol.
AB  - BACKGROUND: AT1 receptor antagonists are clinically effective drugs for the
      treatment of hypertension, cardiovascular, and related disorders. In an attempt
      to identify new AT1 receptor antagonists, a pharmacophore-based virtual screening
      protocol was applied. The pharmacophore models were generated from 30 training
      set compounds. The best model was chosen on the basis of squared correlation
      coefficient of training set and internal test set. The validity of the developed
      model was also ensured using catScramble validation method and external test set
      prediction. RESULTS: The final model highlighted the importance of hydrogen bond
      acceptor, hydrophobic aliphatic, hydrophobic, and ring aromatic features. The
      model satisfied all the statistical criteria such as cost function analysis and
      correlation coefficient. The result of estimated activity for internal and
      external test set compounds reveals that the generated model has high prediction
      capability. The validated pharmacophore model was further used for mining of
      56000 compound database (MiniMaybridge). Total 141 hits were obtained and all the
      hits were checked for druggability, this led to the identification of two active
      druggable AT1 receptor antagonists with diverse structure. CONCLUSION: A highly
      validated pharmacophore model generated in this study identified two novel
      druggable AT1 receptor antagonists. The developed model can also be further used
      for mining of other virtual database.

PMID- 22380005
TI  - Perfectionistic self-presentation, socially prescribed perfectionism, and suicide
      in youth: a test of the perfectionism social disconnection model.
AB  - The role of interpersonal components of perfectionism in suicide outcomes among
      youth was assessed and the Perfectionism Social Disconnection Model (PSDM) was
      tested by determining whether the links between socially prescribed perfectionism
      (SPP) and perfectionistic self-presentation (PSP) and suicide outcomes are
      mediated by experiences of social disconnection, as indicated by social
      hopelessness and being bullied. PSP, trait perfectionism, suicide outcomes, and
      experiences of being bullied and social hopelessness were measured in 152
      psychiatric outpatient children and adolescents. Correlational tests confirmed
      that PSP and SPP were associated with suicide outcomes and these interpersonal
      perfectionism components were associated significantly with bullying and social
      hopelessness. Support was also obtained for the PSDM. The relationship between
      the PSP facets, particularly nondisplay of imperfections, and suicide outcomes
      were mediated by being bullied. Additionally, the relationship between all
      interpersonal components of perfectionism and suicide risk was mediated by social
      hopelessness. Theoretical and clinical implications of interpersonal components
      of perfectionism and social disconnection in suicide outcomes for youth are
      discussed.

PMID- 22380006
TI  - Derrida, and all that jazz.

PMID- 22380008
TI  - Aptamers as remarkable diagnostic and therapeutic agents in cancer treatment.
AB  - Nucleic acid aptamers are molecules that are being used in a large number of
      biomedical applications. Aptamers have the properties to bind to a wide range of
      molecules with high specificity and affinity for their target. These properties
      together with their small size and their ease of synthesis make them very
      attractive and promising for targeting diseases and therapeutic applications.
      Aptamers can serve as cancer diagnostic tools by detecting specific biomarkers,
      circulating cancer cells or imaging diseased tissue. On the other hand, aptamers
      can be used as therapeutic agents due to their potential antagonist activity, or
      as targeting agents. Therefore, they can be designed to deliver antitumor
      molecules such as chemotherapeutic drugs, siRNA or photodynamic therapy
      sensitizers to diseased tissues. Attempts are also made to synthesize aptamers
      targeted nanoplatforms capable to ferry cargo and load onto them both imaging and
      therapeutic functions creating so called nanotheragnostics agents. In the future,
      its seems likely that aptamers will play an important role in diagnosis and
      treatment of several pathologies including cancer.

PMID- 22380009
TI  - In vivo biodistribution, pharmacokinetics, and toxicology of carbon nanotubes.
AB  - Owing to their interesting physical and chemical properties, carbon nanotubes
      (CNTs) have attracted wide attentions in nanomedicine for applications in
      biological sensing, drug delivery, as well as biomedical imaging. The in vivo
      behaviors and toxicology of CNTs in biological systems, which are important
      fundamental questions, although have been intensively studied in recent years,
      remain to be clarified as distinctive results have been reported by various
      teams, confusing the scientific community as well as the public. In this article,
      we review the research on the in vivo behaviors of CNTs, and summarize the
      toxicity studies of CNTs in animals by different groups. Similar to other
      nanomaterials, the in vivo pharmacokinetics and biodistribution of CNTs are
      closely associated with their surface coatings. The excretion of CNTs from
      animals may happen via renal and fecal pathways, depending on the CNT surface
      chemistry, shape, and sizes. Regarding the toxicology of CNTs, which has been a
      debating topic for years, the administration routes, doses, and again the surface
      functionalization are critical to the in vivo toxicity of nanotubes. Much more
      efforts are still required to develop functional CNT bioconjugates with improved
      biocompatible coatings and controllable optimal sizes to achieve fast excretion
      and minimal toxicity, for various applications in biomedicine.

PMID- 22380007
TI  - Influence of hormonal status on substrate utilization at rest and during exercise
      in the female population.
AB  - During exercise, substrate utilization plays a major role in performance and
      disease prevention. The contribution of fat and carbohydrates to energy
      expenditure during exercise is modulated by several factors, including intensity
      and duration of exercise, age, training and diet, but also gender. Because sex
      hormone levels change throughout a woman's lifetime (in connection with puberty,
      the menstrual cycle, use of oral contraceptives and menopause), the female
      population has to be considered specifically in terms of substrate utilization,
      and metabolic and hormonal responses to exercise. Before puberty, there is no
      difference between males and females when it comes to substrate oxidation during
      exercise. This is not the case during adulthood, since women are known to rely
      more on fat than men for the same relative intensity of exercise. Among adult
      women, the menstrual cycle and use of oral contraceptives may influence substrate
      oxidation. While some authors have noted that the luteal phase of the menstrual
      cycle is connected with greater lipid oxidation, compared with the follicular
      stage, other authors have found no difference. Among oral contraceptive users,
      fat oxidation is sometimes increased during prolonged exercise with a concomitant
      rise in lipolytic hormones, as well as growth hormone. If this result is not
      always observed, the type of oral contraceptive (monophasic vs triphasic) and
      hormone doses may be implicated. Menopause represents a hormonal transition in a
      woman's life, leading to a decline in ovarian hormone production. A decrease in
      fat oxidation is consequently observed, and some studies have demonstrated a
      similar respiratory exchange ratio during prolonged exercise in postmenopausal
      women and in men. As is the case during puberty, no sex difference should thus
      appear after menopause in the absence of hormonal replacement therapy (HRT).
      Results concerning women who take HRT remain conflicting. HRT may act on fat loss
      by increasing lipid metabolism, but this depends on how the treatment is
      administered (orally vs transdermally). To better understand the role of ovarian
      hormones in substrate oxidation, studies have made use of animal protocols to
      investigate cellular mechanisms. Estradiol and progesterone seem to have opposite
      effects, with greater lipid oxidation when estradiol is used alone. However, the
      concentrations used (physiological levels or pharmacological doses) may
      considerably modify fuel selection. In cases where conflicting data are observed
      in studies of substrate utilization and prolonged exercise in women,
      methodological reasons must be called into question. Too many parameters, which
      oftentimes are not specified, may modulate substrate utilization and metabolic
      and hormonal responses to prolonged exercise. Although information is generally
      provided about the type of exercise, its duration and the subjects' training
      level, detailed information is not always given about the subjects' nutritional
      state and, more specifically, the hormonal status of female subjects. The primary
      purpose of this review was to identify the impact of hormonal status on substrate
      oxidation among female subjects at rest and during exercise. A second aim was to
      describe gender differences in substrate utilization during exercise.

PMID- 22380010
TI  - Nano-based drug delivery system enhances the oral absorption of lipophilic drugs
      with extensive presystemic metabolism.
AB  - Oral administration remains the most preferred route for the treatment of many
      diseases due to its convenience and adaptability. However, the presystemic
      metabolism may be an important barrier that prevents lipophilic drugs from
      achieving their pharmacological effects following oral delivery. Nano-based drug
      delivery system provides an effective strategy to reduce the presystemic
      metabolism and increase the systemic exposure of lipophilic drugs. In this
      review, we described the physiological factors affecting the presystemic
      metabolism of lipophilic drugs, intestinal transport of nanosystems, strategy of
      nanosystems to avoid the presystemic metabolism, and the current application of
      various oral nanosystems including lipid and polymeric nanocarriers. The nano
      based drug delivery system has a lot of potential for reducing the presystemic
      metabolism and enhancing the bioavailability of orally administrated lipophilic
      drugs.

PMID- 22380011
TI  - Dendrimers in cancer therapeutics and diagnosis.
AB  - Dendrimers represent a class of monodispersed synthetic macromolecules with a
      well defined three-dimensional structure of nanometer dimension in which a series
      of layered branches regularly extend from a central core molecule. Due to their
      precise nanoscale sizes, well-defined branched structures, and various surface
      modifications, dendrimers have been extensively investigated in a wide range of
      applications in the biomedical field, particularly in the therapeutics and
      diagnosis of cancer. This article gives an overview of the recent advances of
      dendrimers and dendrimer-based hybrid nanoparticles for cancer therapeutics and
      diagnosis applications.

PMID- 22380012
TI  - Fluorescent carbon dots and nanodiamonds for biological imaging: preparation,
      application, pharmacokinetics and toxicity.
AB  - The rapid advancement of nanotechnology has brought us some new types of
      fluorescent probes, which are indispensable for bioimaging in life sciences.
      Because of their innate biocompatibility, good resistance against photobleaching,
      long fluorescence lifetime and wide fluorescence spectral region, fluorescent
      carbon quantum dots (C-Dots) and nanosized diamonds (nanodiamonds, NDs) are
      gradually evolving into promising reagents for bioimaging. In this review, we
      summarize the recent achievements in fluorescent C-Dots and NDs with emphases on
      their preparation, properties, imaging application, pharmacokinetics and
      toxicity. Perspectives on further investigations and opportunities to develop C
      Dots and NDs into the safer and more sensitive imaging probes for both living
      cells and animal models are discussed.

PMID- 22380013
TI  - Co-delivery strategies based on multifunctional nanocarriers for cancer therapy.
AB  - Chemotherapy is among the most common means for clinicians in the fight against
      various types of tumors. However, severe toxicity with undesirable toxic effects
      against normal tissues and cells significantly hinders the applications of these
      chemotherapeutic agents and leads to multiple complications for patients. Recent
      developments of nanotechnology-enabled drug delivery platforms allow simultaneous
      delivery of multiple chemotherapeutic agents to target different metabolic
      pathways of tumor cells, thus providing new opportunities for higher therapeutic
      efficacy and lower cytotoxicity. Furthermore, multifunctional nanocarriers can
      also deliver diagnostic agents, including MRI contrast agents and fluorescent
      probes, to achieve cancer diagnosis and therapy at the same time. This present
      review discusses the various aspects of current co-delivery strategies and
      emphasizes the need for novel designs of biocompatible and non or low toxic
      nanocarriers. Further studies on potential adverse effects of various
      nanocarriers are warranted.

PMID- 22380015
TI  - Impacts of nanoparticles on cardiovascular diseases: modulating metabolism and
      function of endothelial cells.
AB  - Endothelial cells have very important functions, one of which is their
      contribution to regulating molecule and nutrient exchanges between the blood and
      peripheral tissues. Dysfunction of endothelial cells plays an essential role in
      the progression of cardiovascular diseases (CVD) such as atherosclerosis and
      coronary heart disease. With the recent progress of nanotechnology, increasing
      numbers of studies have focused on the effects of nanoparticles on CVD. In this
      article, we review the biological characters of endothelial cells, evaluate the
      impacts of nanoparticles on the behavior and functions of endothelial cells,
      analyze advantages and disadvantages of various nanoparticles, and discuss
      potential applications of nanoparticles to CVD treatment.

PMID- 22380014
TI  - Toxicological profile of therapeutic nanodelivery systems.
AB  - Several of the newly developed drug molecules show potent biological activity,
      but exhibit poor pharmacokinetic properties that may hinder their effective
      delivery to the intended site of action. In order to improve their
      pharmacological effect, these molecules can be associated with drug carriers in
      order to overcome these inherent difficulties. An ideal drug delivery agent
      requires therefore biocompatibility, improved solubility of a loaded drug or
      peptide, releasing of the payload at the absorption site and, at the same time,
      leaving undisturbed cell structure and function, and maintaining the
      physiological milieu. By taking advantage of the valuable properties of nanoscale
      delivery systems, such as increased surface area, improved solubility of
      hydrophobic drugs, possibility to encapsulate and protect drugs from degradation
      and reduced immunogenic potential and toxicological effect, new therapeutic
      options can be brought forth and improve the clinical arsenal for numerous
      diseases. The use of nanodelivery systems can even promote the re-investigation
      of pharmacokinetically less favourable, but biologically more active compounds.
      Although very promising, these systems may also encompass inherent toxicological
      issues, mainly due to their size and shape, physical interaction with cellular
      membranes and organelles, immunological reactions, long- or short-term tissue
      accumulation, and degradation products. Pharmaceutical nanodelivery systems, such
      as liposomes, polymeric nanoparticles, dendrimers and mesoporous silica and
      silicon based nanoparticles have shown great potential in preclinical
      applications and several of these nanosystems are even undergoing clinical
      trials. They have been found to combine drug delivery properties with an
      acceptable toxicological profile, which has made them prime candidates for
      several drug delivery approaches. This review aims to provide and correlate the
      toxicological studies with the drug delivery properties of the above mentioned
      nanodelivery systems in particular concerning uptake and accumulation as well as
      the critical aspects in each system regarding their optimal performance, while
      pointing out to the most relevant references.

PMID- 22380016
TI  - Nanoparticles improve biological functions of phthalocyanine photosensitizers
      used for photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a new technology using photodynamic effect for
      disease diagnosis and treatment. It is a two-step technique involving the uptake
      of a photosensitizer by cancer tissue followed by light irradiation that excites
      the photosensitizer to produce highly reactive oxygen species, the latter execute
      apoptosis of cancerous cells. As a second-generation of photosensitizers,
      phthalocyanine demonstrates higher absorption in the 650-800 nm range and short
      tissue accumulation compared to their first generation. However, many potent
      phthalocyanine photosensitizers are hydrophobic and poorly water-soluble, which
      limit their therapeutic applications. As a result, advanced delivery systems and
      different strategies are called for to improve the effectiveness of PDT. Facts
      have proved that using nanoparticles as carries of photosensitizers is a very
      promising route. Nanoparticles have the potentials to increase photosensitizers'
      aqueous solubility, bioavailability and stability, and deliver photosensitizers
      to the target tissues. This article reviewed the commonly-used nanoparticles,
      including colloid gold, quantum dots, paramagnetic nanoparticles, silica-based
      materials, polymer-based nanoparticles, as potential delivery systems for
      phthalocyanine photosensitizers, and summarized the improved biological functions
      of phthalocyanine photosensitizers in PDT.

PMID- 22380017
TI  - Fullerenes for cancer diagnosis and therapy: preparation, biological and clinical
      perspectives.
AB  - Cancer is a major public health problem in the world. There is a great need to
      apply novel technologies and drugs to revolutionize multiple aspects of cancer
      diagnosis and therapy. Advances in nanotechnology and nanomaterials have the
      potential to achieve the objective of early diagnosis and early therapy of cancer
      in the future. During the past few years, fullerene and its derivatives have been
      considered as some of the most promising nanomaterials because of their unique
      properties that enable a variety of medicinal applications. They can deliver
      drugs or small therapeutic molecules to the cancer cells. In this review, we will
      discuss how fullerene derivatives have been introduced into the field of cancer
      diagnosis and therapy. It will be highlighted that fullerene derivatives are used
      as anti-tumor drugs. Furthermore, preparation, characterization, pharmacokinetics
      and bio-distribution of fullerene and its derivatives reported in recent years
      will be summarized.

PMID- 22380018
TI  - QSTR modelling of the acute toxicity of pharmaceuticals to fish.
AB  - Extensive use of pharmaceuticals as human and veterinary medication raises
      concerns for their adverse effects on non-target organisms. The purpose of this
      study was to employ multiple linear regression (MLR) to predict the toxicities of
      a diverse set of pharmaceuticals to fish. The descriptor pool consisted of about
      1500 descriptors calculated using Dragon 5.4, Spartan 06 and Codessa 2.2
      software. Descriptor selection was made by the heuristic method available in
      Codessa 2.2. The data set was divided into training and test sets using Kohonen
      networks. The training set contained approximately 65% of the compounds of the
      full data set (99 compounds). The training set model contained eight descriptors
      from all dimensions, all of which were obtained from Dragon 5.4. The statistical
      parameters of the model for the training set are R(2 )= 0.664, F = 13.588, and
      R(cv)(2) (LOO) = 0.542 while it achieves R(2 )= 0.605 for the test set. The
      training, test and external sets have no response outliers considering the
      standardized residual greater than three. The external validation of the model
      was made with a set of pharmaceuticals obtained from several databases. The
      R(pred)(2) is 0.777, reflecting a relatively good predictive power for the
      external set.

PMID- 22380019
TI  - Nanoparticulate delivery of LHRH analogue for the treatment of prostate cancer.
AB  - Goserelin acetate (Gos) is a luteinizing hormone-releasing hormone agonist, used
      in treatment of prostate cancer in which desired concentration of Gos in blood is
      maintained for longer duration. The aim of this study is to improve the efficacy
      of Gos targeted at the site of action and eliminate the need for frequent
      administration. Gos-encapsulated nanoparticles were fabricated by double
      emulsification process. The physicochemical traits of the nanoparticles including
      morphology, particle size, zeta-potential, entrapment efficiency, and in-vitro
      release profile were studied. The in-vitro cytotoxicity of the blank
      nanoparticles and Gos-loaded nanoparticles were also evaluated on LNCaP cell line
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blank
      methoxy PEG-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles exhibited low
      cytotoxicity, which increased with increase in concentration of Gos-loaded
      nanoparticles. Serum Gos and testosterone levels were analyzed after subcutaneous
      administration in Wistar rats. In-vivo study showed that a sustained serum level
      of Gos successfully suppressed the plasma testosterone concentration to
      castration level. So, it can be concluded that mPEG-PCL nanoparticles might prove
      to be useful for site specific and sustain protein delivery.

PMID- 22380021
TI  - Structure-induced enhancement in electrooxidation of trimetallic FePtAu
      nanoparticles.
AB  - Using FePtAu nanoparticles (NPs) as an example, this Communication demonstrates a
      new structure-control strategy to tune and optimize NP catalysis. The presence of
      Au in FePtAu facilitates FePt structure transformation from chemically disordered
      face-centered cubic (fcc) structure to chemically ordered face-centered
      tetragonal (fct) structure, and further promotes formic acid oxidation reaction
      (FAOR). The fct-FePtAu NPs have mass activity as high as 2809.9 mA/mg Pt and
      retain 92.5% of this activity after a 13 h stability test. They become the most
      efficient NP catalyst ever reported for FAOR. This structure-control strategy can
      be extended to other multimetallic NP systems, providing a general approach to
      advanced NP catalysts with desired activity and durability control for practical
      applications.

PMID- 22380020
TI  - Assessment of cellular oxygen gradients with a panel of phosphorescent oxygen
      sensitive probes.
AB  - The supply of oxygen (O(2)) to respiring tissue, cells, and mitochondria
      regulates metabolism, gene expression, and cell fate. Depending on the cell type
      and mitochondrial function, O(2) gradients between extra- and intracellular
      compartments may vary and play important physiological roles such as the
      regulation of activity of prolyl hydroxylases and adaptive responses to hypoxia.
      Here we present a new methodology for the analysis of localized O(2) gradients in
      cultures of adherent cells, using three phosphorescent Pt-porphyrin based probes
      with different localization. One new O(2) probe targeted to the cell membrane was
      developed and used together with existing MitoXpress and Nano2 probes to monitor
      mean pericellular (PC), extracellular (EC), and intracellular (IC) O(2)
      concentrations, respectively. Mouse fibroblasts and neuronal PC12 cells cultured
      in standard microplates were stained with probes and measured on a commercial
      time-resolved fluorescence reader in phosphorescence lifetime mode. Respiring
      cells exposed to various levels of atmospheric O(2) showed differences in
      oxygenation of their IC, PC, and EC compartments. Experiments with different cell
      numbers and modulation of respiration activity demonstrated that these gradients
      are dynamic and regulated by the O(2) diffusion and consumption rate. The new
      method facilitates the assessment of such gradients.

PMID- 22380023
TI  - A lamotrigine induced toxic epidermal necrolysis in a child.
AB  - Toxic epidermal necrolysis (TEN) is rare, life-threatening skin disorder that
      usually is caused by an adverse drug reaction. The exact pathogenesis of TEN is
      still unknown. Many treatments including prednisolone, cyclosporine and
      intravenous immunoglobulin (IVIG) can be used to halt the disease process. We
      present a 12-year-old girl with epilepsy who developed TEN after about 14 days of
      lamotrigine treatment. Lamotrigine was immediately discontinued. After receiving
      systemic corticosteroid treatment, the patient had a complete recovery.
      Antiepileptic-induced TEN can be mortal in some cases. Thus, we would like to
      point out the importance of early diagnosis and treatment.

PMID- 22380024
TI  - Communication: Fundamental measure theory for hard disks: fluid and solid.
AB  - Two-dimensional hard-particle systems are rather easy to simulate but
      surprisingly difficult to treat by theory. Despite their importance from both
      theoretical and experimental points of view, theoretical approaches are usually
      qualitative or at best semi-quantitative. Here, we present a density functional
      theory based on the ideas of fundamental measure theory for two-dimensional hard
      disk mixtures, which allows for the first time an accurate description of the
      structure of the dense fluid and the equation of state for the solid phase within
      the framework of density functional theory. The properties of the solid phase are
      obtained by freely minimizing the functional.

PMID- 22380025
TI  - Communication: Identical temperature dependence of the time scales of several
      linear-response functions of two glass-forming liquids.
AB  - The frequency-dependent dielectric constant, shear and adiabatic bulk moduli,
      longitudinal thermal expansion coefficient, and longitudinal specific heat have
      been measured for two van der Waals glass-forming liquids, tetramethyl
      tetraphenyl-trisiloxane (DC704) and 5-polyphenyl-4-ether. Within the experimental
      uncertainties the loss-peak frequencies of the measured response functions have
      identical temperature dependence over a range of temperatures, for which the
      Maxwell relaxation time varies more than nine orders of magnitude. The time
      scales are ordered from fastest to slowest as follows: Shear modulus, adiabatic
      bulk modulus, dielectric constant, longitudinal thermal expansion coefficient,
      and longitudinal specific heat. The ordering is discussed in light of the recent
      conjecture that van der Waals liquids are strongly correlating, i.e., approximate
      single-parameter liquids.

PMID- 22380026
TI  - Mapping quantum-classical Liouville equation: projectors and trajectories.
AB  - The evolution of a mixed quantum-classical system is expressed in the mapping
      formalism where discrete quantum states are mapped onto oscillator states,
      resulting in a phase space description of the quantum degrees of freedom. By
      defining projection operators onto the mapping states corresponding to the
      physical quantum states, it is shown that the mapping quantum-classical Liouville
      operator commutes with the projection operator so that the dynamics is confined
      to the physical space. It is also shown that a trajectory-based solution of this
      equation can be constructed that requires the simulation of an ensemble of
      entangled trajectories. An approximation to this evolution equation which retains
      only the Poisson bracket contribution to the evolution operator does admit a
      solution in an ensemble of independent trajectories but it is shown that this
      operator does not commute with the projection operators and the dynamics may take
      the system outside the physical space. The dynamical instabilities, utility, and
      domain of validity of this approximate dynamics are discussed. The effects are
      illustrated by simulations on several quantum systems.

PMID- 22380027
TI  - Can orbital-free density functional theory simulate molecules?
AB  - Orbital-free density functional theory (OFDFT), with its attractive linearly
      scaling computation cost and low prefactor, is one of the most powerful first
      principles methods for simulating large systems (~10(4)-10(6) atoms). However,
      approximating the electron kinetic energy with density functionals limits the
      accuracy and generality of OFDFT compared to Kohn-Sham density functional theory
      (KSDFT). In this work, we test whether the Huang-Carter (HC) kinetic energy
      density functional (KEDF), which contains the physics to properly describe
      covalently bonded semiconductor materials, can also be used to describe covalent
      bonds in molecules. In particular, we calculate a variety of homonuclear diatomic
      molecules with the HC functional within OFDFT. The OFDFT bond dissociation
      energy, equilibrium bond length, and vibrational frequency of these dimers are in
      remarkably good agreement with benchmark KSDFT results, given the lack of
      orbitals in the calculation. We vary the two parameters lambda (controlling the
      reduced density gradient contribution to the nonlocal kernel) and beta (the
      exponent of the density in the nonlocal term) present in the HC KEDF and find
      that the optimal lambda correlates with the magnitude of the highest occupied
      molecular orbital-lowest unoccupied molecular orbital energy gap. Although the HC
      KEDF represents a significant improvement over previous KEDFs in describing
      covalent systems, deficiencies still exist. Despite the similar overall shape of
      the KSDFT and OFDFT ground state electron densities, the electron density within
      the bonding region is still quite different. Furthermore, OFDFT is not yet able
      to give reasonable description of magnetic states. The energy orderings of the
      triplet and singlet states of Si(2) and Al family dimers are not consistent with
      KSDFT or experimental results and the spin polarization distributions also differ
      widely between the two theories.

PMID- 22380028
TI  - Non-Born-Oppenheimer electronic and nuclear densities for a Hooke-Calogero three
      particle model: non-uniqueness of density-derived molecular structure.
AB  - We consider the calculation of non-Born-Oppenheimer, nBO, one-particle densities
      for both electrons and nuclei. We show that the nBO one-particle densities
      evaluated in terms of translationally invariant coordinates are independent of
      the wavefunction describing the motion of center of mass of the whole system. We
      show that they depend, however, on an arbitrary reference point from which the
      positions of the vectors labeling the particles are determined. We examine the
      effect that this arbitrary choice has on the topology of the one-particle density
      by selecting the Hooke-Calogero model of a three-body system for which
      expressions for the one-particle densities can be readily obtained in analytic
      form. We extend this analysis to the one-particle densities obtained from full
      Coulomb interaction wavefunctions for three-body systems. We conclude, in view of
      the fact that there is a close link between the choice of the reference point and
      the topology of one-particle densities that the molecular structure inferred from
      the topology of these densities is not unique. We analyze the behavior of one
      particle densities for the Hooke-Calogero Born-Oppenheimer, BO, wavefunction and
      show that topological transitions are also present in this case for a particular
      mass value of the light particles even though in the BO regime the nuclear masses
      are infinite. In this vein, we argue that the change in topology caused by
      variation of the mass ratio between light and heavy particles does not constitute
      a true indication in the nBO regime of the emergence of molecular structure.

PMID- 22380029
TI  - Reduced density matrix hybrid approach: application to electronic energy
      transfer.
AB  - Electronic energy transfer in the condensed phase, such as that occurring in
      photosynthetic complexes, frequently occurs in regimes where the energy scales of
      the system and environment are similar. This situation provides a challenge to
      theoretical investigation since most approaches are accurate only when a certain
      energetic parameter is small compared to others in the problem. Here we show that
      in these difficult regimes, the Ehrenfest approach provides a good starting point
      for a dynamical description of the energy transfer process due to its ability to
      accurately treat coupling to slow environmental modes. To further improve on the
      accuracy of the Ehrenfest approach, we use our reduced density matrix hybrid
      framework to treat the faster environmental modes quantum mechanically, at the
      level of a perturbative master equation. This combined approach is shown to
      provide an efficient and quantitative description of electronic energy transfer
      in a model dimer and the Fenna-Matthews-Olson complex and is used to investigate
      the effect of environmental preparation on the resulting dynamics.

PMID- 22380031
TI  - Temperature inhomogeneities simulated with multiparticle-collision dynamics.
AB  - The mesoscopic simulation technique known as multiparticle collision dynamics is
      presented as a very appropriate method to simulate complex systems in the
      presence of temperature inhomogeneities. Three different methods to impose the
      temperature gradient are compared and characterized in the parameter landscape.
      Two methods include the interaction of the system with confining walls. The third
      method considers open boundary conditions by imposing energy fluxes. The
      transport of energy characterizing the thermal diffusivity is also investigated.
      The dependence of this transport coefficient on the method parameters and the
      accuracy of existing analytical theories is discussed.

PMID- 22380030
TI  - Basis set convergence of molecular correlation energy differences within the
      random phase approximation.
AB  - The basis set convergence of energy differences obtained from the random phase
      approximation (RPA) to the correlation energy is investigated for a wide range of
      molecular interactions. For dispersion bound systems the basis set incompleteness
      error is most pronounced, as shown for the S22 benchmark [P. Jurecka et al.,
      Phys. Chem. Chem. Phys. 8, 1985 (2006)]. The use of very large basis sets (>
      quintuple-zeta) or extrapolation to the complete basis set (CBS) limit is
      necessary to obtain a reliable estimate of the binding energy for these systems.
      Counterpoise corrected results converge to the same CBS limit, but counterpoise
      correction without extrapolation is insufficient. Core-valence correlations do
      not play a significant role. For medium- and short-range correlation, quadruple
      zeta results are essentially converged, as demonstrated for relative alkane
      conformer energies, reaction energies dominated by intramolecular dispersion,
      isomerization energies, and reaction energies of small organic molecules. Except
      for weakly bound systems, diffuse augmentation almost universally slows down
      basis set convergence. For most RPA applications, quadruple-zeta valence basis
      sets offer a good balance between accuracy and efficiency.

PMID- 22380032
TI  - Canonical transcorrelated theory with projected Slater-type geminals.
AB  - An effective Hamiltonian perturbed with explicit interelectronic correlation is
      derived from similarity transformation of Hamiltonian using a unitary operator
      with Slater-type geminals. The Slater-type geminal is projected onto the
      excitation (and deexcitation) component as in the F12 theory. Simplification is
      made by truncating higher-body operators, resulting in a correlated Hamiltonian
      which is Hermitian and has exactly the same complexity as the original
      Hamiltonian in the second quantized form. It can thus be easily combined with
      arbitrary correlation models proposed to date. The present approach constructs a
      singularity-free Hamiltonian a priori, similarly to the so-called transcorrelated
      theory, while the use of the canonical transformation assures that the effective
      Hamiltonian is two-body and Hermite. Our theory is naturally extensible to
      multireference calculations on the basis of the generalized normal ordering. The
      construction of the effective Hamiltonian is non-iterative. The numerical
      assessments demonstrate that the present scheme improves the basis set
      convergence of the post-mean-field calculations at a similar rate to the
      explicitly correlated methods proposed by others that couple geminals and
      conventional excitations.

PMID- 22380033
TI  - Dynamic hyperpolarizability calculations of large systems: the linear-scaling
      divide-and-conquer approach.
AB  - We report a linear-scaling computation method for evaluating the dynamic first
      hyperpolarizability beta based on the divide-and-conquer (DC) method. In the
      present scheme, we utilized the quasi-density-matrix expression derived from
      Wigner's (2n + 1) rule for beta, where the quasi-density matrices are constructed
      from the solution obtained via the DC time-dependent self-consistent field (TD
      SCF) method [T. Touma, M. Kobayashi, and H. Nakai, Chem. Phys. Lett. 485, 247
      (2010)]. Numerical evaluation of pi-conjugated and saturated organic chain
      systems verified that the present scheme considerably reduces the computational
      time for the beta evaluation with a slight loss of accuracy, even around the
      singular frequency appearing at the electronic excitation energy. This evaluation
      indicates that the present linear-scaling TD-SCF scheme can also be used to
      estimate the molecular excitation energy. Furthermore, we succeeded in accurately
      evaluating the macroscopic second-harmonic generation coefficient of the
      polyvinylidene fluoride from the molecular (hyper)polarizabilities.

PMID- 22380034
TI  - Natural polarizability and flexibility via explicit valency: the case of water.
AB  - As the dominant physiological solvent, water drives the folding of biological
      macromolecules, influences conformational changes, determines the ionization
      states of surface groups, actively participates in catalytic events, and provides
      "wires" for long-range proton transfer. Elucidation of all these roles calls for
      atomistic simulations. However, currently available methods do not lend
      themselves to efficient simulation of proton transfer events, or even
      polarizability and flexibility. Here, we report that an explicit account of
      valency can provide a unified description for the polarizability, flexibility,
      and dissociability of water in one intuitive and efficient setting. We call this
      approach LEWIS, after the chemical theory that inspires the use of valence
      electron pairs. In this paper, we provide details of the method, the choice of
      the training set, and predictions for the neat ambient liquid, with emphasis on
      structure, dynamics, and polarization. LEWIS water provides a good description of
      bulk properties, and dipolar and quadrupolar responses.

PMID- 22380035
TI  - Stochastic self-assembly of incommensurate clusters.
AB  - Nucleation and molecular aggregation are important processes in numerous physical
      and biological systems. In many applications, these processes often take place in
      confined spaces, involving a finite number of particles. Analogous to treatments
      of stochastic chemical reactions, we examine the classic problem of homogeneous
      nucleation and self-assembly by deriving and analyzing a fully discrete
      stochastic master equation. We enumerate the highest probability steady states,
      and derive exact analytical formulae for quenched and equilibrium mean cluster
      size distributions. Upon comparison with results obtained from the associated
      mass-action Becker-Doring equations, we find striking differences between the two
      corresponding equilibrium mean cluster concentrations. These differences depend
      primarily on the divisibility of the total available mass by the maximum allowed
      cluster size, and the remainder. When such mass "incommensurability" arises, a
      single remainder particle can "emulsify" the system by significantly broadening
      the equilibrium mean cluster size distribution. This discreteness-induced
      broadening effect is periodic in the total mass of the system but arises even
      when the system size is asymptotically large, provided the ratio of the total
      mass to the maximum cluster size is finite. Ironically, classic mass-action
      equations are fairly accurate in the coarsening regime, before equilibrium is
      reached, despite the presence of large stochastic fluctuations found via kinetic
      Monte-Carlo simulations. Our findings define a new scaling regime in which
      results from classic mass-action theories are qualitatively inaccurate, even in
      the limit of large total system size.

PMID- 22380036
TI  - Electromagnetically induced transparency with quantum interferometry.
AB  - We have shown that electromagnetically induced transparency can be achieved by
      control-probe interferometry using two delayed phase-locked ultrashort pulses.
      Two vibrational wavepackets on the excited state, excited by two delayed phase
      locked ultrashort pulses, interfere constructively or destructively leading to
      enhancement or suppression of absorption to a selective set of vibrational
      levels. Depending on the phase difference and the delay between the pulses with
      same carrier frequency, one can design different transparency windows between
      absorption peaks at consecutive even(odd) vibrational levels by eliminating
      absorption at odd(even) vibrational levels. We have shown that by switching the
      phase difference of two delayed femtosecond pulses, one can switch to complete
      elimination of absorption from enhanced absorption to a particular set of
      vibrational levels in the excited state. Thus, switching of transparency through
      window between odd vibrational levels to that between even vibrational levels is
      possible. By properly choosing the temporal width and the carrier frequency of
      the pulses, lossless transmission of complete or bands of frequencies of the
      pulses can be achieved through these transparency windows. Hence, designing of
      single- or multi-mode transparency windows in NaH molecule is feasible by control
      probe quantum interferometry.

PMID- 22380037
TI  - In search of the next Holy Grail of polyoxide chemistry: explicitly correlated ab
      initio full quartic force fields for HOOH, HOOOH, HOOOOH, and their
      isotopologues.
AB  - Explicitly correlated ab initio methods have been used to compute full quartic
      force fields for the three chain minima for HOOOOH, which are found to lie within
      1 kcal mol(-1). The CCSD(T)-F12 method with the cc-pVTZ-F12 basis set was used to
      compute equilibrium structures, anharmonic vibrational frequencies, and
      rotational constants for HOOH, HOOOH, and three chain isomers of HOOOOH, with the
      two former force fields being used as benchmarks for the latter three. The full
      quartic force fields were computed in such a way as to yield fundamental
      frequencies for all isotopologues at once. The present research confirms the
      recent experimental identification of HOOOH and provides reliable force fields in
      support of future experimental work on the enigmatic bonding paradigms involved
      in the HOOOOH chain.

PMID- 22380038
TI  - Collisional electron transfer to photoexcited acceptor radical anions.
AB  - In this article, we show that photoexcitation of radical anions facilitates
      electron transfer from sodium atoms in femtosecond encounters. Thus, excitation
      of 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) and fluorinated TCNQ (TCNQ-F(4))
      anions to the second optically active state at 478 nm led to increases in the
      yields of dianions of about 20% and 10%, respectively. Photoexcitation with a
      nanosecond-long laser pulse was done a few microseconds before the ions entered
      the sodium collision cell so that none of the ions would be in any of the
      initially reached doublet-excited states. We suggest an explanation for the
      higher electron capture cross section based on the formation of long-lived
      quartet state anions. Excitation of TCNQ anions within the lowest-energy
      absorption band, where there are no accessible quartet states, led instead to a
      lower yield of dianions. There are at least three explanations for the lower
      dianion yields: (1) Depletion of the monoanion beam due to photodetachment after
      the absorption of minimum two photons; (2) Formation of short-lived vibrationally
      excited dianions that decay by electron autodetachment prior to identification;
      and (3) Lower electron capture cross sections of vibrationally excited
      monoanions. Similar losses in dianion signal can occur at 478 nm so the actual
      yield of dianions at this wavelength due to the population of quartet states is
      therefore greater than that observed. Our methodology devises a more efficient
      route for the production of molecular dianions, and at the same time it may
      provide information on long-lived electronic states.

PMID- 22380039
TI  - Overtone-induced dissociation and isomerization dynamics of the hydroxymethyl
      radical (CH2OH and CD2OH). I. A theoretical study.
AB  - The dissociation of the hydroxymethyl radical, CH(2)OH, and its isotopolog,
      CD(2)OH, following the excitation of high OH stretch overtones is studied by
      quasi-classical molecular dynamics calculations using a global potential energy
      surface (PES) fitted to ab initio calculations. The PES includes CH(2)OH and
      CH(3)O minima, dissociation products, and all relevant barriers. Its analysis
      shows that the transition states for OH bond fission and isomerization are both
      very close in energy to the excited vibrational levels reached in recent
      experiments and involve significant geometry changes relative to the CH(2)OH
      equilibrium structure. The energies of key stationary points are refined using
      high-level electronic structure calculations. Vibrational energies and
      wavefunctions are computed by coupled anharmonic vibrational calculations. They
      show that high OH-stretch overtones are mixed with other modes. Consequently,
      trajectory calculations carried out at energies about ~3000 cm(-1) above the
      barriers reveal that despite initial excitation of the OH stretch, the direct OH
      bond fission is relatively slow (10 ps) and a considerable fraction of the
      radicals undergoes isomerization to the methoxy radical. The computed
      dissociation energies are: D(0)(CH(2)OH -> CH(2)O + H) = 10,188 cm(-1),
      D(0)(CD(2)OH -> CD(2)O + H) = 10,167 cm(-1), D(0)(CD(2)OH -> CHDO + D) = 10,787
      cm(-1). All are in excellent agreement with the experimental results. For
      CH(2)OH, the barriers for the direct OH bond fission and isomerization are:
      14,205 and 13,839 cm(-1), respectively.

PMID- 22380040
TI  - Overtone-induced dissociation and isomerization dynamics of the hydroxymethyl
      radical (CH2OH and CD2OH). II. Velocity map imaging studies.
AB  - The dissociation of the hydroxymethyl radical, CH(2)OH, and its isotopolog,
      CD(2)OH, following excitation in the 4nu(1) region (OH stretch overtone, near
      13,600 cm(-1)) was studied using sliced velocity map imaging. A new vibrational
      band near 13,660 cm(-1) arising from interaction with the antisymmetric CH
      stretch was discovered for CH(2)OH. In CD(2)OH dissociation, D atom products
      (correlated with CHDO) were detected, providing the first experimental evidence
      of isomerization in the CH(2)OH <-> CH(3)O (CD(2)OH <-> CHD(2)O) system. Analysis
      of the H (D) fragment kinetic energy distributions shows that the rovibrational
      state distributions in the formaldehyde cofragments are different for the OH bond
      fission and isomerization pathways. Isomerization is responsible for 10%-30% of
      dissociation events in all studied cases, and its contribution depends on the
      excited vibrational level of the radical. Accurate dissociation energies were
      determined: D(0)(CH(2)OH -> CH(2)O + H) = 10,160 +/- 70 cm(-1), D(0)(CD(2)OH ->
      CD(2)O + H) = 10,135 +/- 70 cm(-1), D(0)(CD(2)OH -> CHDO + D) = 10,760 +/- 60 cm(
      1).

PMID- 22380041
TI  - Surface temperature effect on the scattering of D2(v = 0, j = 0)-Cu(111) system.
AB  - We perform four-dimensional (4D?2D) as well as six-dimensional (6D) quantum
      dynamics on a parametrically time- and temperature-dependent effective
      Hamiltonian for D(2)(v, j)-Cu(111) system, where such effective potential has
      been derived through a mean-field approach between molecular degrees of freedom
      and surface modes with Bose-Einstein probability factor for their initial state
      distribution. We present the convergence of the theoretically calculated sticking
      probabilities employing 4D?2D quantum dynamics with increasing number of surface
      atoms as well as layers for rigid surface and the surface at a particular
      temperature, where the temperature-dependent sticking probabilities appear
      exclusively dictated by those surface modes directed along the Z-axis. The
      sticking and state-to-state transition probabilities obtained from 6D quantum
      dynamics are shown as a function of initial kinetic energy of the diatom at
      different surface temperature. Theoretically calculated sticking probabilities
      display the similar trend with the experimentally measured one.

PMID- 22380042
TI  - Low-energy electron collisions with glycine.
AB  - We report cross sections for elastic electron scattering by gas phase glycine
      (neutral form), obtained with the Schwinger multichannel method. The present
      results are the first obtained with a new implementation that combines
      parallelization with OpenMP directives and pseudopotentials. The position of the
      well known pi* shape resonance ranged from 2.3 eV to 2.8 eV depending on the
      polarization model and conformer. For the most stable isomer, the present result
      (2.4 eV) is in fair agreement with electron transmission spectroscopy assignments
      (1.93 +/- 0.05 eV) and available calculations. Our results also point out a shape
      resonance around 9.5 eV in the A' symmetry that would be weakly coupled to
      vibrations of the hydroxyl group. Since electron attachment to a broad and lower
      lying sigma* orbital located on the OH bond has been suggested the underlying
      mechanism leading to dissociative electron attachment at low energies, we sought
      for a shape resonance around ~4 eV. Though we obtained cross sections with the
      target molecule at the equilibrium geometry and with stretched OH bond lengths,
      least-squares fits to the calculated eigenphase sums did not point out signatures
      of this anion state (though, in principle, it could be hidden in the large
      background). The low energy (~1 eV) integral cross section strongly scales as the
      bond length is stretched, and this could indicate a virtual state pole, since
      dipole supported bound states are not expected at the geometries addressed here.

PMID- 22380043
TI  - Ab initio study of dynamical E * e Jahn-Teller and spin-orbit coupling effects in
      the transition-metal trifluorides TiF3, CrF3, and NiF3.
AB  - Multiconfiguration ab initio methods have been employed to study the effects of
      Jahn-Teller (JT) and spin-orbit (SO) coupling in the transition-metal
      trifluorides TiF(3), CrF(3), and NiF(3), which possess spatially doubly
      degenerate excited states ((M)E) of even spin multiplicities (M = 2 or 4). The
      ground states of TiF(3), CrF(3), and NiF(3) are nondegenerate and exhibit minima
      of D(3h) symmetry. Potential-energy surfaces of spatially degenerate excited
      states have been calculated using the state-averaged complete-active-space self
      consistent-field method. SO coupling is described by the matrix elements of the
      Breit-Pauli operator. Linear and higher order JT coupling constants for the JT
      active bending and stretching modes as well as SO-coupling constants have been
      determined. Vibronic spectra of JT-active excited electronic states have been
      calculated, using JT Hamiltonians for trigonal systems with inclusion of SO
      coupling. The effect of higher order (up to sixth order) JT couplings on the
      vibronic spectra has been investigated for selected electronic states and
      vibrational modes with particularly strong JT couplings. While the weak SO
      couplings in TiF(3) and CrF(3) are almost completely quenched by the strong JT
      couplings, the stronger SO coupling in NiF(3) is only partially quenched by JT
      coupling.

PMID- 22380044
TI  - Nuclear spin selective laser control of rotational and torsional dynamics.
AB  - We explore the possibility of controlling rotational-torsional dynamics of non
      rigid molecules with strong, non-resonant laser pulses and demonstrate that
      transient, laser-induced torsional alignment depends on the nuclear spin of the
      molecule. Consequently, nuclear spin isomers can be manipulated selectively by a
      sequence of time-delayed laser pulses. We show that two pulses with different
      polarization directions can induce either overall rotation or internal torsion,
      depending on the nuclear spin. Nuclear spin selective control of the angular
      momentum distribution may open new ways to separate and explore nuclear spin
      isomers of polyatomic molecules.

PMID- 22380045
TI  - A new ab initio intermolecular potential energy surface and predicted rotational
      spectra of the Ar-H2S complex.
AB  - We report a reliable three-dimensional ab initio intermolecular potential energy
      surface for the Ar-H(2)S complex with H(2)S monomer fixed at its experimental
      average structure. The potential energies were evaluated using the supermolecular
      approach at the coupled-cluster level with a large basis set including bond
      functions. The full counterpoise procedure was used to correct the basis set
      superposition error. The potential has a planar T-shaped global minimum with a
      well depth of 177.48 cm(-1) at the intermolecular distance of 3.72 A. An
      additional planar local minimum is also found and is separated from the global
      minimum with an energy barrier with a height of 47.46 cm(-1). The combined radial
      discrete variable representation/angular finite basis representation method and
      the Lanczos algorithm were employed to calculate the rovibrational energy levels
      for three isotopic species of Ar-H(2)S complexes (Ar-H(2)(32)S, Ar-H(2)(33)S, and
      Ar-H(2)(34)S). The rotational transition frequencies and structural parameters
      for the three isotopomers were also determined for the ground and the first
      excited states, which are all in good agreement with the available experimental
      values.

PMID- 22380046
TI  - Ab initio properties of MgAlk (Alk = Li, Na, K, Rb, Cs).
AB  - High level ab initio calculations are performed on the ground electronic state of
      diatomic molecules MgAlk (Alk = Li, Na, K, Rb, Cs). Potential energy curves and
      dipole moment functions are determined making use of the single-reference
      unrestricted and restricted coupled-cluster methods with large basis sets. Basic
      spectroscopic properties of the ground electronic states are derived from ro
      vibrational bound state calculations.

PMID- 22380047
TI  - A set of molecular models for alkali and halide ions in aqueous solution.
AB  - This work presents new molecular models for alkali and halide ions in aqueous
      solution. The force fields were parameterized with respect to the reduced liquid
      solution density at 293.15 K and 1 bar, considering all possible ion combinations
      simultaneously. The experimental target data are reproduced with a high accuracy
      over a wide range of salinity. The ion models predict structural properties of
      electrolyte solutions well, such as pair correlation functions and hydration
      numbers. The force fields provide good predictions of the properties studied here
      in combination with different models for water.

PMID- 22380048
TI  - The effect of the spatial nonlocality of the Kirkwood g-factor on the
      determination of the long wavelength dielectric functions in dipolar fluids.
AB  - The Kirkwood g-factor that determines the long wavelength dielectric constant of
      a simple, isotropic, translationally invariant dipolar fluid is given by an
      integral of a dipole-dipole correlation function over a spherical region of a
      nonzero radius R(K) chosen such that any further increase in the radius leads to
      no change in the value of the integral, thereby defining a Kirkwood correlation
      length R(K). For radii less than the correlation length the integral defines a
      radius dependent (nonlocal) Kirkwood g-factor, implying a nonlocal dielectric
      function. The nonlocal nature of these quantities has important consequences for
      the determination of the long wavelength dielectric function from dipole
      fluctuations via the Kirkwood-Frohlich connection. The dipole-dipole correlation
      function (the volume dipole auto-correlation function) commonly used in this
      determination involves particles residing solely within a sphere of radius R,
      unlike the correct correlation function which involves either a single particle
      with those particles in a spherical volume of radius R(K) or those particles in a
      spherical volume of radius R with those residing within a spherical volume of
      radius R+R(K). A procedure is suggested for extracting the infinite system dipole
      dipole correlation function from results of simulations performed on finite
      spherical samples. Using some results reported in the recent literature, relative
      to the accurate correlation function the commonly used correlation function
      ranges from 27% too small for a sphere having a radius comparable to the Kirkwood
      correlation length to 4% too small at a radius of seven times that correlation
      length. As a result, the apparent dielectric constants, as determined by the
      conventional procedure of using the fluctuations of the sum of dipoles in a
      finite fixed volume, are also too small. This suggests that a dielectric constant
      extracted from computer simulations using a total dipole-total dipole correlation
      function in a given volume with other geometries and/or boundary conditions will
      result in similar errors.

PMID- 22380049
TI  - Unexpected effects of third-order cross-terms in heteronuclear spin systems under
      simultaneous radio-frequency irradiation and magic-angle spinning NMR.
AB  - We recently noted [R. K. Harris, P. Hodgkinson, V. Zorin, J.-N. Dumez, B. Elena,
      L. Emsley, E. Salager, and R. Stein, Magn. Reson. Chem. 48, S103 (2010)]
      anomalous shifts in apparent (1)H chemical shifts in experiments using (1)H
      homonuclear decoupling sequences to acquire high-resolution (1)H NMR spectra for
      organic solids under magic-angle spinning (MAS). Analogous effects were also
      observed in numerical simulations of model (13)C,(1)H spin systems under
      homonuclear decoupling and involving large (13)C,(1)H dipolar couplings. While
      the heteronuclear coupling is generally assumed to be efficiently suppressed by
      sample spinning at the magic angle, we show that under conditions typically used
      in solid-state NMR, there is a significant third-order cross-term from this
      coupling under the conditions of simultaneous MAS and homonuclear decoupling for
      spins directly bonded to (1)H. This term, which is of the order of 100 Hz under
      typical conditions, explains the anomalous behaviour observed on both (1)H and
      (13)C spins, including the fast dephasing observed in (13)C{(1)H} heteronuclear
      spin-echo experiments under (1)H homonuclear decoupling. Strategies for
      minimising the impact of this effect are also discussed.

PMID- 22380050
TI  - Universality of the onset of activated transport in Lennard-Jones liquids with
      tunable coordination: implications for the effects of pressure and directional
      bonding on the crossover to activated transport, configurational entropy, and
      fragility of glassforming liquids.
AB  - We establish, via classical density functional theory, that the crossover to
      activated transport in liquids takes place when the depth of the metastable
      minimum in the free energy corresponding to long-lived aperiodic structures
      reaches a certain near universal value. We show that the particle vibrational
      displacement is strongly correlated with this depth in a broad range of pressure
      and temperature, thus providing basis for a Lindemann-like criterion for the
      onset of activated transport in liquids. The configurational entropy at the
      crossover temperature T(cr), too, is found to be nearly system-independent,
      consistent with the random first order transition theory. We show that to
      reproduce existing data for the pressure dependence of T(cr), the liquid must
      increase its coordination with pressure. Upon increasing pressure at fixed
      coordination, the liquid's fragility is predicted to exhibit re-entrant behavior.
      This prediction is consistent with glycerol data but is in contrast with data in
      several organic liquids and polymers, whose fragility monotonically decreases
      with pressure in the so far accessed pressure range. Allowing for increase in
      coordination with pressure mitigates the disagreement, owing to the resulting
      decrease in the thermal expansivity. Finally, we rationalize the correlation
      between the isobaric and isochoric fragilities put forth by Casalini and Roland
      [Phys. Rev. E 72, 031503 (2005)] and make predictions on the limiting behavior of
      the fragility at high pressure.

PMID- 22380051
TI  - Dynamical heterogeneity in a highly supercooled liquid under a sheared situation.
AB  - In the present study, we performed molecular dynamics simulations and
      investigated dynamical heterogeneity in a supercooled liquid under a steady shear
      flow. Dynamical heterogeneity can be characterized by three quantities: the
      correlation length xi(4)(t), the intensity chi(4)(t), and the lifetime
      tau(hetero)(t). We quantified all three quantities by means of the correlation
      functions of the particle dynamics, i.e., the four-point correlation functions,
      which are extended to the sheared condition. Here, to define the local dynamics,
      we used two time intervals t = tau(alpha) and tau(ngp); tau(alpha) is the alpha
      relaxation time, and tau(ngp) is the time at which the non-Gaussian parameter of
      the Van Hove self-correlation function is maximized. We discovered that all three
      quantities (xi(4)(t), chi(4)(t), and tau(hetero)(t)) decrease as the shear rate
      gamma of the steady shear flow increases. For the time interval t = tau(alpha),
      the scalings xi(4)(tau(alpha))~gamma(-0.08), chi(4)(tau(alpha))~gamma(-0.26), and
      tau(hetero)(tau(alpha))~gamma(-0.88) were obtained. The steady shear flow
      suppresses the heterogeneous structure as well as the lifetime of the dynamical
      heterogeneity. In addition, we demonstrated that all three quantities in the
      sheared non-equilibrium state can be mapped onto those in the equilibrium state
      through the alpha-relaxation time tau(alpha). This finding means that the same
      relation between tau(alpha) and three quantities holds in both the equilibrium
      state and the sheared non-equilibrium state and therefore proposes that the
      dynamical heterogeneity can play a similar role in the drastic change of
      tau(alpha) due to not only the temperature but also the shear rate.

PMID- 22380052
TI  - Molecular dynamics and kinetic study of carbon coagulation in the release wave of
      detonation products.
AB  - We present a combined molecular dynamics and kinetic study of a carbon cluster
      aggregation process in thermodynamic conditions relevant for the detonation
      products of oxygen deficient explosives. Molecular dynamics simulations with the
      LCBOPII potential under gigapascal pressure and high temperatures indicate that
      (i) the cluster motion in the detonation gas is compatible with Brownian
      diffusion and (ii) the coalescence probability is 100% for two clusters entering
      the interaction cutoff distance. We used these results for a subsequent kinetic
      study with the Smoluchowski model, with realistic models applied for the physical
      parameters such as viscosity and cluster size. We found that purely aggregational
      kinetics yield too fast clustering, with moderate influence of the model
      parameters. In agreement with previous studies, the introduction of surface
      reactivity through a simple kinetic model is necessary to approach the clustering
      time scales suggested by experiments (1000 atoms after 100 ns, 10 000 atoms after
      1 MUs). However, these models fail to reach all experimental criteria
      simultaneously and more complex modelling of the surface process seems desirable
      to go beyond these current limitations.

PMID- 22380053
TI  - Sensitivity of nucleation phenomena on range of interaction potential.
AB  - Theoretical and computational investigations of nucleation have been plagued by
      the sensitivity of the phase diagram to the range of the interaction potential.
      As the surface tension depends strongly on the range of interaction potential and
      as the classical nucleation theory (CNT) predicts the free energy barrier to be
      directly proportional to the cube of the surface tension, one expects a strong
      sensitivity of nucleation barrier to the range of the potential; however, CNT
      leaves many aspects unexplored. We find for gas-liquid nucleation in Lennard
      Jones system that on increasing the range of interaction the kinetic spinodal
      (KS) (where the mechanism of nucleation changes from activated to barrierless)
      shifts deeper into the metastable region. Therefore the system remains metastable
      for larger value of supersaturation and this allows one to explore the high
      metastable region without encountering the KS. On increasing the range of
      interaction, both the critical cluster size and pre-critical minima in the free
      energy surface of kth largest cluster, at respective kinetic spinodals, shift
      towards smaller cluster size. In order to separate surface tension contribution
      to the increase in the barrier from other non-trivial factors, we introduce a new
      scaling form for surface tension and use it to capture both the temperature and
      the interaction range dependence of surface tension. Surprisingly, we find only a
      weak non-trivial contribution from other factors to the free energy barrier of
      nucleation.

PMID- 22380054
TI  - Adsorbed liposome deformation studied with quartz crystal microbalance.
AB  - Deformation of surface-adsorbed liposomes is an important parameter that governs
      the kinetics of their transformations, but one that is very difficult to measure
      in the case of nm-size liposomes. We investigate the deformation of dimyristoyl
      phosphatidyl choline liposomes by quartz crystal microbalance (QCM) as a function
      of temperature and show that it follows the dependence of this lipid's bending
      modulus on temperature, as expected from theoretical considerations. To
      corroborate our approach, we model QCM response from adsorbed liposomes by
      explicitly considering their shape and mechanical properties.

PMID- 22380055
TI  - Theoretical study of the geometries and dissociation energies of molecular water
      on neutral aluminum clusters Al(n) (n = 2-25).
AB  - Geometries and dissociation energies of water molecules on Al(n) (n = 2-25)
      clusters were investigated using density functional theory with all electron
      relativistic spin-polarized calculations under the generalized gradient
      approximation. An extensive structure search was performed to identify the low
      energy conformations of Al(n)H(2)O complexes for each size. Optimal adsorption
      sites were assigned for low-energy isomers of the clusters. Size and site
      specific dependences were studied for the Al(n)H(2)O complexes in stabilities,
      geometries, adsorption energies, dissociation energies, Al-O bond lengths, and
      other characteristic quantities. The stabilities and geometries revealed that H
      atom in H(2)O is not inclined to bond with Al atoms. The most stable Al(n)H(2)O
      configurations for each size tend to correspond to the most stable bare Al(n)
      cluster except of Al(6) and Al(24) clusters. The HO bond lengths increase
      generally 0.01 A with respect to the isolated H(2)O in all of the adsorption
      complexes. The dissociation energy of an isolated H(2)O into HO and H was 5.39
      eV, which decreased about two-thirds to the energy range of 0.83-2.12 eV with the
      help of Al(n) clusters. In spite of the fluctuations, the dissociation energies
      of Al(n)H(2)O complexes rise with the size increasing as a whole. In addition, we
      also found that the bare Al(n) clusters with high vertical ionization potentials
      usually have high dissociation energies of H(2)O in the corresponding adsorption
      models. The energetically preferred spin-multiplicity of all the odd-n Al(n)H(2)O
      complexes is doublet, and it is singlet for all the even-n complexes with
      exception of Al(2)H(2)O which is triplet.

PMID- 22380056
TI  - Promoter effect of BaO on CO oxidation on PdO surfaces.
AB  - The effect of bulk BaO promoter on CO oxidation activity of palladium oxide phase
      was studied by density functional calculations. A series of BaO(100) supported
      Pd(x)O(y) thin layer models were constructed, and energy profiles for CO
      oxidation on the films were calculated and compared with corresponding profiles
      for the most stable PdO bulk surfaces PdO(100) and PdO(101). The most stable of
      the thin films typically exhibit the same PdO(100) and PdO(101) surface planes;
      the PdO(100) dominates already with double layer thickness. The supporting
      promoter improves the CO oxidation activity of the Pd(x)O(y) phase via a direct
      electronic effect and introduced structural strain and corrugation. Changes in CO
      adsorption strength are reflected in oxidation energy barriers, and the promoting
      effect of even 0.3 eV can be seen locally. Easier oxygen vacancy formation may
      partially facilitate the reaction.

PMID- 22380057
TI  - Similarities and differences among the models proposed for real electrodes in the
      Poisson-Nernst-Planck theory.
AB  - The ionic distribution induced by an external field is investigated by means of
      the Poisson-Nernst-Planck model, by taking into account the non-blocking
      properties of the limiting electrodes. Three types of models proposed for the
      description of real electrodes are considered. The first two assume an ionic
      current on the electrodes proportional to the variation of the bulk density of
      ions and to the surface electric field, respectively. The third model assumes
      that the sample is limited by perfectly blocking electrodes with a true
      resistance in parallel to the cell. Here we show that the first two models are
      equivalent, in the sense that it is possible to find a phenomenological parameter
      by means of which the predictions of the two models, for what concerns the
      spectra of the real and imaginary parts of the impedance of the cell, are the
      same. On the contrary, the third model is equivalent to the others only if the
      conduction current across the electrodes is small with respect to the
      displacement current.

PMID- 22380058
TI  - Molecular dynamics simulations of charged nanoparticle self-assembly at ionic
      liquid-water and ionic liquid-oil interfaces.
AB  - Nanoparticle self-assembly at liquid-liquid interfaces can be significantly
      affected by the individual nanoparticle charges. This is particularly true at
      ionic liquid (IL) based interfaces, where Coulombic forces play a major role.
      Employing 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]) as a
      model IL, we have studied the self-assembly of hydrophobic nanoparticles with
      different surface charges at the IL/water and IL/oil (hexane) interfaces using
      molecular dynamics simulations. In the IL/water system, the nanoparticles were
      initially dispersed in the water phase but quickly equilibrated at the interface,
      somewhat in favor of the IL phase. This preference was lessened with increased
      nanoparticle charge. In the IL/hexane system, all charged nanoparticles
      interacted with the IL to some extent, whereas the uncharged nanoparticles
      remained primarily in the hexane phase. Potential of mean force calculations
      supported the observations from the equilibrium studies and provided new insights
      into the interactions of the nanoparticles and ionic liquid based interfaces.

PMID- 22380059
TI  - Simulation of crack propagation in alumina with ab initio based polarizable force
      field.
AB  - We present an effective atomic interaction potential for crystalline alpha
      Al(2)O(3) generated by the program potfit. The Wolf direct, pairwise summation
      method with spherical truncation is used for electrostatic interactions. The
      polarizability of oxygen atoms is included by use of the Tangney-Scandolo
      interatomic force field approach. The potential is optimized to reproduce the
      forces, energies, and stresses in relaxed and strained configurations as well as
      {0001}, {1010}, and {1120} surfaces of Al(2)O(3). Details of the force field
      generation are given, and its validation is demonstrated. We apply the developed
      potential to investigate crack propagation in alpha-Al(2)O(3) single crystals.

PMID- 22380060
TI  - An ellipsoid-chain model for conjugated polymer solutions.
AB  - We propose an ellipsoid-chain model which may be routinely parameterized to
      capture large-scale properties of semiflexible, amphiphilic conjugated polymers
      in various solvent media. The model naturally utilizes the defect locations as
      pivotal centers connecting adjacent ellipsoids (each currently representing ten
      monomer units), and a variant umbrella-sampling scheme is employed to construct
      the potentials of mean force (PMF) for specific solvent media using atomistic
      dynamics data and simplex optimization. The performances, both efficacy and
      efficiency, of the model are thoroughly evaluated by comparing the simulation
      results on long, single-chain (i.e., 300-mer) structures with those from two
      existing, finer-grained models for a standard conjugated polymer (i.e., poly(2
      methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) or MEH-PPV) in two distinct
      solvents (i.e., chloroform or toluene) as well as a hybrid, binary-solvent medium
      (i.e., chloroform/toluene = 1:1 in number density). The coarse-grained Monte
      Carlo (CGMC) simulation of the ellipsoid-chain model is shown to be the most
      efficient--about 300 times faster than the coarse-grained molecular dynamics
      (CGMD) simulation of the finest CG model that employs explicit solvents--in
      capturing elementary single-chain structures for both single-solvent media, and
      is a few times faster than the coarse-grained Langevin dynamics (CGLD) simulation
      of another implicit-solvent polymer model with a slightly greater coarse-graining
      level than in the CGMD simulation. For the binary-solvent system considered,
      however, both of the two implicit-solvent schemes (i.e., CGMC and CGLD) fail to
      capture the effects of conspicuous concentration fluctuations near the polymer
      solvent interface, arising from a pronounced coupling between the solvent
      molecules and different parts of the polymer. Essential physical implications are
      elaborated on the success as well as the failure of the two implicit-solvent CG
      schemes under varying solvent conditions. Within the ellipsoid-chain model, the
      impact of synthesized defects on local segmental ordering as well as bulk chain
      conformation is also scrutinized, and essential consequences in practical
      applications discussed. In future perspectives, we remark on strategy that takes
      advantage of the coordination among various CG models and simulation schemes to
      warrant computational efficiency and accuracy, with the anticipated capability of
      simulating larger-scale, many-chain aggregate systems.

PMID- 22380061
TI  - Effect of secondary structure on the self-assembly of amphiphilic molecules: a
      multiscale simulation study.
AB  - The self-assembly of amphiphilic molecules is of interest from a fundamental and
      practical standpoint. There has been recent interest in a class of molecules made
      from beta-amino acids (which contain an additional backbone carbon atom when
      compared with natural amino acids). Block copolymers of beta-peptides, where one
      block is hydrophobic and the other is hydrophilic, self-assemble into micelles.
      In this work, we use computer simulations to provide insight into the effect of
      secondary structure on the self-assembly of these molecules. Atomistic
      simulations for the free energy of association of a pair of molecules show that a
      homochiral hydrophobic block promotes self assembly compared to a heterochiral
      hydrophobic block, consistent with experiment. Simulations of a coarse-grained
      model show that these molecules spontaneously form spherical micelles.

PMID- 22380062
TI  - Many-body interactions between particles in a polydisperse polymer fluid.
AB  - We use a continuum chain model and develop an analytical theory for the
      interaction between many spheres immersed in a fluid of ideal polydisperse
      polymers. Assuming local spherical symmetry of the polymer field about each
      particle, combined with a local approximation, compact expressions are derived
      for the many-body interaction between the spheres. We use a mean-field
      approximation to investigate the fluid-fluid phase diagram for the mixture.

PMID- 22380063
TI  - Dynamic exchange of counterions of polystyrene sulfonate.
AB  - Adopting a cationic fluorescent molecule, rhodamine 6G, as the probe of the
      counterions of the model anionic polyelectrolyte (sodium polystyrene sulfonate,
      PSSNa), the diffusion of the counterion probes inside the solution of PSSNa was
      studied by fluorescence correlation spectroscopy. Two species of the counterion
      probes with different diffusion coefficient were discovered--the freely diffusing
      probes and the probes bound to the PSS(-) chains. The concentration fraction of
      these two species was found to change with the concentration and molecular weight
      of PSSNa. The results show that the counterion binding to the PSS(-) chain is
      enhanced with the increase of polymer concentration, attributed to the result of
      the lowered translational entropic penalty at higher polymer concentrations. The
      counterion binding is also enhanced with the increase of molecular weight, and
      the origin was attributed to the chain end effect to the counterion distribution.
      The results indicate the dynamic exchange process between the free counterions
      and the bound ones, which is further evidenced by the replacement of the bound
      probes by the elevated salt levels in the solution.

PMID- 22380064
TI  - On the inverse temperature transition and development of an entropic elastomeric
      force of the elastin mimetic peptide [LGGVG](3, 7).
AB  - We report on a molecular dynamics simulation based study of the thermal and
      mechanical properties of the elastin mimetic peptide [LGGVG](n) (n = 3, 7). Our
      findings indicate that this peptide undergoes an inverse temperature transition
      as the temperature is raised from ~20  degrees C to 42  degrees C. The thermal
      behavior is similar to what has been observed in other well studied short mimetic
      peptides of elastin. Both [LGGVG](n) (n = 3, 7) peptides exhibit an increase in
      the number of side chain contacts and peptide-peptide hydrogen bonds when the
      temperature is raised from ~20  degrees C to 42  degrees C. These observations
      are accompanied by a decrease in the number of proximal water molecules and
      number of peptide-water hydrogen bonds. This work also reports on a comparison of
      the thermal and mechanical properties of [LGGVG](3) and [VPGVG](3) and quantifies
      the interaction with surrounding waters of hydration under mechanically strained
      conditions. It is demonstrated, via a quasi-harmonic approach, that both model
      peptides exhibit a reduction in the population of low-frequency modes and an
      increase in population of high-frequency modes upon elongation. The shift in
      population of frequency modes causes the peptide entropy to decrease upon
      elongation and is responsible for the development of an entropic force that gives
      rise to elasticity. These observations are in disagreement with a previously
      published notion that model elastin peptides, such as [VPGVG](18), increase in
      entropy upon elongation.

PMID- 22380065
TI  - Dipolar response of hydrated proteins.
AB  - The paper presents an analytical theory and numerical simulations of the dipolar
      response of hydrated proteins in solution. We calculate the effective dielectric
      constant representing the average dipole moment induced at the protein by a
      uniform external field. The dielectric constant shows a remarkable variation
      among the proteins, changing from 0.5 for ubiquitin to 640 for cytochrome c. The
      former value implies a negative dipolar susceptibility, that is a dia-electric
      dipolar response and negative dielectrophoresis. It means that ubiquitin,
      carrying an average dipole of ?240 D, is expected to repel from the region of a
      stronger electric field. This outcome is the result of a negative cross
      correlation between the protein and water dipoles, compensating for the positive
      variance of the intrinsic protein dipole in the overall dipolar susceptibility.
      In contrast to the neutral ubiquitin, charged proteins studied here show para
      electric dipolar response and positive dielectrophoresis. The study suggests that
      the dipolar response of proteins in solution is strongly affected by the coupling
      of the protein surface charge to the hydration water. The protein-water dipolar
      cross-correlations are long-ranged, extending ~2 nm from the protein surface into
      the bulk. A similar correlation length of about 1 nm is seen for the
      electrostatic potential produced by the hydration water inside the protein. The
      analysis of numerical simulations suggests that the polarization of the protein
      water interface is highly heterogeneous and does not follow the standard
      dielectric results for cavities carved in dielectrics. The polarization of the
      water shell gains in importance, relative to the intrinsic protein dipole, at
      high frequencies, above the protein Debye peak. The induced interfacial dipole
      can be either parallel or antiparallel to the protein dipole, depending on the
      distribution of the protein surface charge. As a result, the high-frequency
      absorption of the protein solution can be either higher or lower than the
      absorption of water. Both scenarios have been experimentally observed in the THz
      window of radiation.

PMID- 22380066
TI  - Note: Theoretical mixing coefficients for hybrid functionals.

PMID- 22380070
TI  - Perspective: Time scales and clocks: "Invited review article: The statistical
      modeling of atomic clocks and the design of time scales" [Rev. Sci. Instrum. 83,
      021101 (2012)] and "Invited review article: The uncertainty in the realization
      and dissemination of the SI second from a systems point of view" [Rev. Sci.
      Instrum. 83, 021102 (2012)].

PMID- 22380071
TI  - Invited review article: The statistical modeling of atomic clocks and the design
      of time scales.
AB  - I will show how the statistical models that are used to describe the performance
      of atomic clocks are derived from their internal design. These statistical models
      form the basis for time scales, which are used to define international time
      scales such as International Atomic Time and Coordinated Universal Time. These
      international time scales are realized by ensembles of clocks at national
      laboratories such as the National Institute of Standards and Technology, and I
      will describe how ensembles of atomic clocks are characterized and managed.

PMID- 22380072
TI  - Invited review article: The uncertainty in the realization and dissemination of
      the SI second from a systems point of view.
AB  - The uncertainty (accuracy) in the realization and dissemination of the SI second
      is determined by the characteristics of three major components: (1) primary
      frequency standards, (2) time scale flywheels that provide a continuously present
      frequency reference, and (3) frequency transfer systems. Currently these three
      systems contribute at approximately equal levels in the mid 10(-16) range over 20
      to 30 days of averaging time to the practical delivery of the SI second to the
      most demanding users. Any significant improvement in one system requires similar
      improvements in the other two systems in order for most users to see the full
      benefits.

PMID- 22380073
TI  - A capillary absorption spectrometer for stable carbon isotope ratio (13C/12C)
      analysis in very small samples.
AB  - A capillary absorption spectrometer (CAS) suitable for IR laser isotope analysis
      of small CO(2) samples is presented. The system employs a continuous-wave (cw)
      quantum cascade laser to study nearly adjacent rovibrational transitions of
      different isotopologues of CO(2) near 2307 cm(-1) (4.34 MUm). This initial CAS
      system can achieve relative isotopic precision of about 10 ppm (13)C, or ~1 per
      thousand (per mil in delta notation relative to Vienna Pee Dee Belemnite) with 20
      100 picomoles of entrained sample within the hollow waveguide for CO(2)
      concentrations ~400-750 ppm. Isotopic analyses of such gas fills in a 1-mm ID
      hollow waveguide of 0.8 m overall physical path length can be carried out down to
      ~2 Torr. Overall (13)C/(12)C ratios can be calibrated to ~2 per thousand accuracy
      with diluted CO(2) standards. A novel, low-cost method to reduce cw-fringing
      noise resulting from multipath distortions in the hollow waveguide is presented,
      which allows weak absorbance features to be studied at the few ppm level (peak-to
      rms) after 1000 scans are co-added in ~10 s. The CAS is meant to work directly
      with converted CO(2) samples from a laser ablation-catalytic combustion micro
      sampler to provide (13)C/(12)C ratios of small biological isolates currently
      operating with spatial resolutions ~50 MUm.

PMID- 22380074
TI  - The electron spectro-microscopy beamline at National Synchrotron Light Source II:
      a wide photon energy range, micro-focusing beamline for photoelectron spectro
      microscopies.
AB  - A comprehensive optical design for a high-resolution, high-flux, wide-energy
      range, micro-focused beamline working in the vacuum ultraviolet and soft x-ray
      photon energy range is proposed. The beamline is to provide monochromatic
      radiation to three photoelectron microscopes: a full-field x-ray photoelectron
      emission microscope and two scanning instruments, one dedicated to angle resolved
      photoemission spectroscopy (MU-ARPES) and one for ambient pressure x-ray
      photoelectron spectroscopy and scanning photoelectron microscopy (AP-XPS/SPEM).
      Microfocusing is achieved with state of the art elliptical cylinders, obtaining a
      spot size of 1 MUm for ARPES and 0.5 MUm for AP-XPS/SPEM. A detailed ray tracing
      analysis quantitatively evaluates the overall beamline performances.

PMID- 22380075
TI  - Penning traps with unitary architecture for storage of highly charged ions.
AB  - Penning traps are made extremely compact by embedding rare-earth permanent
      magnets in the electrode structure. Axially-oriented NdFeB magnets are used in
      unitary architectures that couple the electric and magnetic components into an
      integrated structure. We have constructed a two-magnet Penning trap with radial
      access to enable the use of laser or atomic beams, as well as the collection of
      light. An experimental apparatus equipped with ion optics is installed at the
      NIST electron beam ion trap (EBIT) facility, constrained to fit within 1 meter at
      the end of a horizontal beamline for transporting highly charged ions. Highly
      charged ions of neon and argon, extracted with initial energies up to 4000 eV per
      unit charge, are captured and stored to study the confinement properties of a one
      magnet trap and a two-magnet trap. Design considerations and some test results
      are discussed.

PMID- 22380076
TI  - Precise real-time polarization measurement of terahertz electromagnetic waves by
      a spinning electro-optic sensor.
AB  - We propose and develop a method to quickly and precisely determine the
      polarization direction of coherent terahertz electromagnetic waves generated by
      femtosecond laser pulses. The measurement system consists of a conventional
      terahertz time-domain spectroscopy system with the electro-optic (EO) sampling
      method, but we add a new functionality in the EO crystal which is continuously
      rotating with the angular frequency omega. We find a simple yet useful
      formulation of the EO signal as a function of the crystal orientation, which
      enables a lock-in-like detection of both the electric-field amplitude and the
      absolute polarization direction of the terahertz waves with respect to the probe
      laser pulse polarization direction at the same time. The single measurement
      finishes around two periods of the crystal rotations (~21 ms), and we
      experimentally prove that the accuracy of the polarization measurement does not
      suffer from the long-term amplitude fluctuation of the terahertz pulses.
      Distribution of the measured polarization directions by repeating the
      measurements is excellently fitted by a gaussian distribution function with a
      standard deviation of sigma = 0.56 degrees . The developed technique is useful
      for the fast direct determination of the polarization state of the terahertz
      electromagnetic waves for polarization imaging applications as well as the
      precise terahertz Faraday or Kerr rotation spectroscopy.

PMID- 22380077
TI  - Hard x-ray monochromator with milli-electron volt bandwidth for high-resolution
      diffraction studies of diamond crystals.
AB  - We report on design and performance of a high-resolution x-ray monochromator with
      a spectral bandwidth of DeltaE(X) ? 1.5 meV, which operates at x-ray energies in
      the vicinity of the backscattering (Bragg) energy E(H) = 13.903 keV of the (008)
      reflection in diamond. The monochromator is utilized for high-energy-resolution
      diffraction characterization of diamond crystals as elements of advanced x-ray
      crystal optics for synchrotrons and x-ray free-electron lasers. The monochromator
      and the related controls are made portable such that they can be installed and
      operated at any appropriate synchrotron beamline equipped with a pre
      monochromator.

PMID- 22380078
TI  - A momentum imaging microscope for dissociative electron attachment.
AB  - We describe an experimental approach to image the three-dimensional (3D) momentum
      distribution of the negative ions arising from dissociative electron attachment
      (DEA). The experimental apparatus employs a low energy pulsed electron gun, an
      effusive gas source and a 4pi solid-angle ion momentum imaging spectrometer
      consisting of a pulsed ion extraction field, an electrostatic lens, and a time-
      and position-sensitive detector. The time-of-flight and impact position of each
      negative ion are measured event by event in order to image the full 3D ion
      momentum sphere. The system performance is tested by measuring the anion momentum
      distributions from two DEA resonances, namely H(-) from H(2)O(-) ((2)B(1)) and O(
      ) from O(2)(-) ((2)Pi(u)). The results are compared with existing experimental
      and theoretical data.

PMID- 22380079
TI  - Narrow linewidth tunable external cavity diode laser using wide bandwidth filter.
AB  - We demonstrate single mode operation of an external cavity diode laser (ECDL)
      employing an interference filter with multimode bandwidth for mode selection. A
      cateye reflector maximizes feedback efficiency and reduces susceptibility to
      intra-cavity optical misalignment. Narrow linewidths of 26 kHz are observed, and
      the laser can be tuned over 14 nm using a single 785 nm filter, without
      alteration of the output beam direction. The cateye reflector and filter allow a
      mechanically rigid design free of significant mechanical resonances, illustrated
      by comparison of the frequency noise spectrum with that of a common Littrow ECDL
      design using a diffraction grating and kinematic mount.

PMID- 22380080
TI  - Measurement of probe displacement to the thermal resolution limit in photonic
      force microscopy using a miniature quadrant photodetector.
AB  - A photonic force microscope comprises of an optically trapped micro-probe and a
      position detection system to track the motion of the probe. Signal collection for
      motion detection is often carried out using the backscattered light off the probe
      however, this mode has problems of low S/N due to the small backscattering cross
      sections of the micro-probes typically used. The position sensors often used in
      these cases are quadrant photodetectors. To ensure maximum sensitivity of such
      detectors, it would help if the detector size matched with the detection beam
      radius after the condenser lens (which for backscattered detection would be the
      trapping objective itself). To suit this condition, we have used a miniature
      displacement sensor whose dimensions makes it ideal to work with 1:1 images of
      micrometer-sized trapped probes in the backscattering detection mode. The
      detector is based on the quadrant photo-integrated chip in the optical pick-up
      head of a compact disc player. Using this detector, we measured absolute
      displacements of an optically trapped 1.1 MUm probe with a resolution of ~10 nm
      for a bandwidth of 10 Hz at 95% significance without any sample or laser
      stabilization. We characterized our optical trap for different sized probes by
      measuring the power spectrum for each probe to 1% accuracy, and found that for
      1.1 MUm diameter probes, the noise in our position measurement matched the
      thermal resolution limit for averaging times up to 10 ms. We also achieved a
      linear response range of around 385 nm with cross talk between axes ?4% for 1.1
      MUm diameter probes. The detector has extremely high bandwidth (few MHz) and low
      optical power threshold-other factors that can lead to its widespread use in
      photonic force microscopy.

PMID- 22380081
TI  - Development of soft x-ray time-resolved photoemission spectroscopy system with a
      two-dimensional angle-resolved time-of-flight analyzer at SPring-8 BL07LSU.
AB  - We have developed a soft x-ray time-resolved photoemission spectroscopy system
      using synchrotron radiation (SR) at SPring-8 BL07LSU and an ultrashort pulse
      laser system. Two-dimensional angle-resolved measurements were performed with a
      time-of-flight-type analyzer. The photoemission spectroscopy system is
      synchronized to light pulses of SR and laser using a time control unit. The
      performance of the instrument is demonstrated by mapping the band structure of a
      Si(111) crystal over the surface Brillouin zones and observing relaxation of the
      surface photo-voltage effect using the pump (laser) and probe (SR) method.

PMID- 22380082
TI  - Compact terahertz passive spectrometer with wideband superconductor-insulator
      superconductor mixer.
AB  - We developed a compact terahertz (THz) spectrometer with a superconductor
      insulator-superconductor (SIS) mixer, aiming to realize a portable and highly
      sensitive spectrometer to detect dangerous gases at disaster sites. The receiver
      cryostat which incorporates the SIS mixer and a small cryocooler except for a
      helium compressor has a weight of 27 kg and dimensions of 200 mm * 270 mm * 690
      mm. In spite of the small cooling capacity of the cryocooler, the SIS mixer is
      successfully cooled lower than 4 K, and the temperature variation is suppressed
      for the sensitive measurement. By adopting a frequency sweeping system using
      photonic local oscillator, we demonstrated a spectroscopic measurement of CH(3)CN
      gas in 0.2-0.5 THz range.

PMID- 22380083
TI  - Characteristics of low-energy ion beams extracted from a wire electrode geometry.
AB  - Beams of argon ions with energies less than 50 eV were extracted from an ion
      source through a wire electrode extractor geometry. A retarding potential energy
      analyzer (RPEA) was constructed in order to characterize the extracted ion beams.
      The single aperture RPEA was used to determine the ion energy distribution
      function, the mean ion energy and the ion beam energy spread. The multi-cusp hot
      cathode ion source was capable of producing a low electron temperature gas
      discharge to form quiescent plasmas from which ion beam energy as low as 5 eV was
      realized. At 50 V extraction potential and 0.1 A discharge current, the ion beam
      current density was around 0.37 mA/cm(2) with an energy spread of 3.6 V or 6.5%
      of the mean ion energy. The maximum ion beam current density extracted from the
      source was 0.57 mA/cm(2) for a 50 eV ion beam and 1.78 mA/cm(2) for a 100 eV ion
      beam.

PMID- 22380084
TI  - The dependence of extracted current on discharge gas pressure in neutral beam ion
      sources on HL-2A tokamak.
AB  - The discharge gas pressure is a key factor to influence the extracted current of
      ion source. In this paper, the dependence of extracted current on discharge gas
      pressure was investigated in detail at different arc discharge currents. The
      discharge gas pressure with a very broad range (0.1 Pa-2.7 Pa) was scanned for
      the first time. It is turned out that, with the increasing of discharge gas
      pressure, the extracted current increases and the arc voltage decreases at
      different arc currents; however, when the discharge gas pressure exceeds a
      certain value, the extracted current decreases. For the same discharge gas
      pressure, the higher the arc current, the higher the arc voltage and the
      extracted current are. The arc efficiency was also calculated, and its dependence
      on gas pressure was almost the same with the dependence of extracted current on
      gas pressure, but at the same discharge gas pressure, the lower the arc current,
      the higher the arc efficiency is and the lower the extracted current is.

PMID- 22380085
TI  - Simulations of ionization in a hot cavity surface ion source.
AB  - A new numerical Monte Carlo method based model of a hot cavity surface ionization
      ion source is presented in this paper. The model, intended to support the studies
      on ionization phenomena in a widely used class of ion sources, takes into account
      geometry of the ion source and extraction system, ionizer temperature and other
      features. The results of ion source efficiency calculations for various
      configurations of the extraction field are reviewed. The dominant role of the
      ionizer region near the extraction opening is described. Simulated dependences of
      ionization efficiency on the working parameters like ionizer length and
      temperature, ionization potential of the substance, and extraction voltage are
      discussed. A good agreement of the experimental data (e.g., influence of ionizer
      temperature, current-voltage curve) and the predictions of the model is found. It
      is also shown that the contribution to the ionization yield from impact of
      thermionic electrons accelerated by the extraction field may be significant,
      especially for the substances of small surface ionization coefficient. The
      simulation results are compared to the predictions of different theoretical
      models of the ion source--the obtained simulation data are in accordance both
      with a well-known Kirchner formula and the so called spherical ionizer model.

PMID- 22380086
TI  - Measurement of ion and electron temperatures in plasma blobs by using an improved
      ion sensitive probe system and statistical analysis methods.
AB  - We have measured ion temperature as well as electron temperature in plasma blobs
      observed in a linear plasma device by using an improved ion sensitive probe.
      Current-voltage characteristics of the ion sensitive probe inside and outside
      plasma blobs were re-constructed with a conditional sampling method. It is
      clearly found that both ion and electron temperatures in plasma blobs decrease
      more slowly in a cross-field direction than those in a bulk plasma without plasma
      blobs.

PMID- 22380087
TI  - Tracer-encapsulated solid pellet injection system.
AB  - The method of tracer-encapsulated solid pellet (TESPEL) is now flourishing in
      various fields. The original purpose to study impurity transport without giving
      substantial perturbation on the plasma is implemented successfully for years. In
      addition to this, TESPEL is being intensively applied to study thermal
      (especially non-local) transport, high energy particles with the use of TESPEL
      ablation cloud, and spectroscopy from the viewpoint of atomic data. It is now
      further growing up to the utilization of multiple tracer methods which was not
      planned at the initial phase of the project. The proof-of-principle experiment
      using triple tracers has been successfully implemented. This opens a way to
      compare the Z dependence or mass dependence of impurity transport. In this
      article, as TESPEL is used in a variety of fields, the TESPEL injection system is
      summarized together with the method of TESPEL production, TESPEL storage disk,
      TESPEL guide system, and the differential pumping system. Also, the observation
      system for TESPEL flight and TESPEL ablation is explained.

PMID- 22380088
TI  - Electric field-perturbation measurement of the interaction between two laser
      induced plasmas.
AB  - The interaction between two ns-laser-induced plasmas in air at the early-stage of
      expansion has been analyzed by using a method based on the direct measurement of
      the perturbation of an externally applied electric field. In this experimental
      method, the plasmas were produced by focusing two laser beams between the plates
      of a parallel-plane-charged capacitor. These plasmas produce a perturbation in
      the electric field of the capacitor which can be measured as a voltage change
      across a resistor connected to the ground plate. It was found that for delays
      shorter than 5 ns, the interaction between plasmas is mainly due to the
      interaction of the dipole-charge distribution of each plasma. For longer time
      delays, the shielding effect was dominant.

PMID- 22380089
TI  - Collection of solid and gaseous samples to diagnose inertial confinement fusion
      implosions.
AB  - Collection of representative samples of debris following inertial confinement
      fusion implosions in order to diagnose implosion conditions and efficacy is a
      challenging endeavor because of the unique conditions within the target chamber
      such as unconverted laser light, intense pulse of x-rays, physical chunks of
      debris, and other ablative effects. We present collection of gas samples
      following an implosion for the first time. High collection fractions for noble
      gases were achieved. We also present collection of solid debris samples on flat
      plate collectors. Geometrical collection efficiencies for Au hohlraum material
      were achieved and collection of capsule debris (Be and Cu) was also observed.
      Asymmetric debris distributions were observed for Au and Be samples. Collection
      of Be capsule debris was higher for solid collectors viewing the capsule through
      the laser entrance hole in the hohlraum than for solid collectors viewing the
      capsule around the waist of the hohlraum. Collection of Au hohlraum material
      showed the opposite pattern: more Au debris was collected around the waist than
      through the laser entrance hole. The solid debris collectors were not optimized
      for minimal Cu backgrounds, which limited the conclusions about the symmetry of
      the Cu debris. The quality of the data limited conclusions on chemical
      fractionation effects within the burning, expanding, and then cooling plasma.

PMID- 22380090
TI  - A technique for measuring the propagation of a supersonic radiation front in foam
      via spatially resolved spectral imaging of a tracer layer.
AB  - We present a technique for measuring the propagation of a supersonic radiation
      front in low-density foam, where the lack of motion of the objects in its wake
      makes it difficult to determine its location. We illuminate a thin tracer foil
      embedded in the foam with a broadband x-ray source, and measure its changing
      absorption of these x rays as it ionizes. We record both spatial and spectral
      information of the heated tracer, and thus obtain its ionization state as a
      function of distance along the front propagation direction. We extrapolate this
      information to determine the state of the foam and the location of the radiation
      front. We present the experimental configuration used to test this technique at
      the Omega laser facility along with experimental results.

PMID- 22380091
TI  - First measurement of electron temperature from signal ratios in a double-pass
      Thomson scattering system.
AB  - This paper presents an experimental demonstration to determine electron
      temperature (T(e)) with unknown spectral sensitivity (transmissivity) in a
      Thomson scattering system. In this method, a double-pass scattering configuration
      is used and the scattered lights from each pass (with different scattering
      angles) are measured separately. T(e) can be determined from the ratio of the
      signal intensities without knowing a real chromatic dependence in the
      sensitivity. Note that the wavelength range for each spectral channel must be
      known. This method was applied to the TST-2 Thomson scattering system. As a
      result, T(e) measured from the ratio (T(e,r)) and T(e) measured from a standard
      method (T(e,s)) showed a good agreement with <?T(e,r) - T(e,s)?/T(e,s)> = 7.3%.

PMID- 22380092
TI  - Continuous wave cavity ring down spectroscopy measurements of velocity
      distribution functions of argon ions in a helicon plasma.
AB  - We report continuous wave cavity ring down spectroscopy (CW-CRDS) measurements of
      ion velocity distribution functions (VDFs) in low pressure argon helicon plasma
      (magnetic field strength of 600 G, T(e) ~ 4 eV and n ~ 5 * 10(11) cm(-3)). Laser
      induced fluorescence (LIF) is routinely used to measure VDFs of argon ions, argon
      neutrals, helium neutrals, and xenon ions in helicon sources. Here, we describe a
      CW-CRDS diagnostic based on a narrow line width, tunable diode laser as an
      alternative technique to measure VDFs in similar regimes but where LIF is
      inapplicable. Being an ultra-sensitive, cavity enhanced absorption spectroscopic
      technique; CW-CRDS can also provide a direct quantitative measurement of the
      absolute metastable state density. The proof of principle CW-CRDS measurements
      presented here are of the Doppler broadened absorption spectrum of Ar II at
      668.6138 nm. Extrapolating from these initial measurements, it is expected that
      this diagnostic is suitable for neutrals and ions in plasmas ranging in density
      from 1 * 10(9) cm(-3) to 1 * 10(13) cm(-3) and target species temperatures less
      than 20 eV.

PMID- 22380093
TI  - A new TriBeam system for three-dimensional multimodal materials analysis.
AB  - The unique capabilities of ultrashort pulse femtosecond lasers have been
      integrated with a focused ion beam (FIB) platform to create a new system for
      rapid 3D materials analysis. The femtosecond laser allows for in situ layer-by
      layer material ablation with high material removal rates. The high pulse
      frequency (1 kHz) of ultrashort (150 fs) laser pulses can induce material
      ablation with virtually no thermal damage to the surrounding area, permitting
      high resolution imaging, as well as crystallographic and elemental analysis,
      without intermediate surface preparation or removal of the sample from the
      chamber. The TriBeam system combines the high resolution and broad detector
      capabilities of the DualBeam(TM) microscope with the high material removal rates
      of the femtosecond laser, allowing 3D datasets to be acquired at rates 4-6 orders
      of magnitude faster than 3D FIB datasets. Design features that permit coupling of
      laser and electron optics systems and positioning of a stage in the multiple
      analysis positions are discussed. Initial in situ multilayer data are presented.

PMID- 22380094
TI  - Effectiveness of frequency mapping on 28 nm device broken scan chain failures.
AB  - Frequency mapping methodology is an effective diagnostic tool for detection of
      manufacturing defects in scan chains. It analyses reflected laser modulations
      from toggling scan cells to localize defective scan path or scan cell. In this
      paper, we demonstrate experimentally that the use of solid immersion lens
      technology to enhance signal and spatial resolution is not a prerequisite for
      this technique up till 28 nm technology node. We present case studies to show the
      effectiveness of frequency mapping for detecting systematic and random broken
      scan chain failures on a 28 nm technology node test chip. We achieved 81% success
      rate in this methodology.

PMID- 22380095
TI  - A nanopositioner for scanning probe microscopy: the KoalaDrive.
AB  - We present a new type of piezoelectric nanopositioner called KoalaDrive which can
      have a diameter less than 2.5 mm and a length smaller than 10 mm. The new
      operating principle provides a smooth travel sequence and avoids shaking which is
      intrinsic to nanopositioners based on inertial motion with sawtooth driving
      signals. In scanning probe microscopy, the KoalaDrive can be used for the coarse
      approach of the tip or sensor towards the sample. Inserting the KoalaDrive in a
      piezo tube for xyz-scanning integrates a complete scanning tunneling microscope
      (STM) inside a 4  mm outer diameter piezo tube of <10 mm length. The use of the
      KoalaDrive makes the scanning probe microscopy design ultracompact and
      accordingly leads to a high mechanical stability. The drive is UHV, low
      temperature, and magnetic field compatible. The compactness of the KoalaDrive
      allows building a multi-tip STM as small as a single tip STM.

PMID- 22380096
TI  - 3D mechanical measurements with an atomic force microscope on 1D structures.
AB  - We have developed a simple method to characterize the mechanical properties of
      three dimensional nanostructures, such as nanorods standing up from a substrate.
      With an atomic force microscope the cantilever probe is used to deflect a
      horizontally aligned nanorod at different positions along the nanorod, using the
      apex of the cantilever itself rather than the tip normally used for probing
      surfaces. This enables accurate determination of nanostructures' spring constant.
      From these measurements, Young's modulus is found on many individual nanorods
      with different geometrical and material structures in a short time. Based on this
      method Young's modulus of carbon nanofibers and epitaxial grown III-V nanowires
      has been determined.

PMID- 22380097
TI  - The long range voice coil atomic force microscope.
AB  - Most current atomic force microscopes (AFMs) use piezoelectric ceramics for scan
      actuation. Piezoelectric ceramics provide precision motion with fast response to
      applied voltage potential. A drawback to piezoelectric ceramics is their
      inherently limited ranges. For many samples this is a nonissue, as imaging the
      nanoscale details is the goal. However, a key advantage of AFM over other
      microscopy techniques is its ability to image biological samples in aqueous
      buffer. Many biological specimens have topography for which the range of
      piezoactuated stages is limiting, a notable example of which is bone. In this
      article, we present the use of voice coils in scan actuation for an actuation
      range in the Z-axis an order of magnitude larger than any AFM commercially
      available today. The increased scan size will allow for imaging an important new
      variety of samples, including bone fractures.

PMID- 22380098
TI  - Constant tip-surface distance with atomic force microscopy via quality factor
      feedback.
AB  - The atomic force microscope (AFM) is a powerful and widely used instrument to
      image topography and measure forces at the micrometer and nanometer length scale.
      Because of the high degree of operating accuracy required of the instrument,
      small thermal and mechanical drifts of the cantilever and piezoactuator systems
      hamper measurements as the AFM tip drifts spatially relative to the sample
      surface. To compensate for the drift, we control the tip-surface distance by
      monitoring the cantilever quality factor (Q) in a closed loop. Brownian thermal
      fluctuations provide sufficient actuation to accurately determine cantilever Q by
      fitting the thermal noise spectrum to a Lorentzian function. We show that the
      cantilever damping is sufficiently affected by the tip-surface distance so that
      the tip position of soft cantilevers can be maintained within 40 nm of a setpoint
      in air and within 3 nm in water with 95% reliability. Utilizing this method to
      hover the tip above a sample surface, we have the capability to study sensitive
      interactions at the nanometer length scale over long periods of time.

PMID- 22380099
TI  - Quantitative comparison of two independent lateral force calibration techniques
      for the atomic force microscope.
AB  - Two independent lateral-force calibration methods for the atomic force microscope
      (AFM)--the hammerhead (HH) technique and the diamagnetic lateral force calibrator
      (D-LFC)--are systematically compared and found to agree to within 5 % or less,
      but with precision limited to about 15 %, using four different tee-shaped HH
      reference probes. The limitations of each method, both of which offer independent
      yet feasible paths toward traceable accuracy, are discussed and investigated. We
      find that stiff cantilevers may produce inconsistent D-LFC values through the
      application of excessively high normal loads. In addition, D-LFC results vary
      when the method is implemented using different modes of AFM feedback control,
      constant height and constant force modes, where the latter is more consistent
      with the HH method and closer to typical experimental conditions. Specifically,
      for the D-LFC apparatus used here, calibration in constant height mode introduced
      errors up to 14 %. In constant force mode using a relatively stiff cantilever, we
      observed an ~ 4 % systematic error per MUN of applied load for loads <= 1 MUN.
      The issue of excessive load typically emerges for cantilevers whose flexural
      spring constant is large compared with the normal spring constant of the D-LFC
      setup (such that relatively small cantilever flexural displacements produce
      relatively large loads). Overall, the HH method carries a larger uncertainty,
      which is dominated by uncertainty in measurement of the flexural spring constant
      of the HH cantilever as well as in the effective length dimension of the
      cantilever probe. The D-LFC method relies on fewer parameters and thus has fewer
      uncertainties associated with it. We thus show that it is the preferred method of
      the two, as long as care is taken to perform the calibration in constant force
      mode with low applied loads.

PMID- 22380100
TI  - Long-time stability of a low-energy electron diffraction spin polarization
      analyzer for magnetic imaging.
AB  - The time stability of a polarization analyzer that is used for imaging of
      magnetic structures in a scanning electron microscope with spin polarization
      analysis (spin-SEM or SEMPA) is investigated. The detector is based on the
      diffraction of low-energy electrons at a W(100) crystal at 104.5 eV (LEED
      detector). Due to the adsorption of hydrogen from residual gas, a change of the
      scattering conditions is found that causes an angular shift of the LEED beams as
      well as changes of intensity. The quality factor, which describes the efficiency
      of the detector in SEMPA application, however, is found to be almost constant up
      to a hydrogen coverage of theta ~ 0.25. This gives stable working conditions
      within roughly 1 h at vacuum conditions of 10(-10) mbar.

PMID- 22380101
TI  - A plastic miniature x-ray emission spectrometer based on the cylindrical von
      Hamos geometry.
AB  - We present a short working distance miniature x-ray emission spectrometer
      (miniXES) based on the cylindrical von Hamos geometry. We describe the general
      design principles for the spectrometer and detail a specific implementation that
      covers Kbeta and valence level emission from Fe. Large spatial and angular access
      to the sample region provides compatibility with environmental chambers,
      microprobe, and pump/probe measurements. The primary spectrometer structure and
      optic is plastic, printed using a 3-dimensional rapid-prototype machine. The
      spectrometer is inexpensive to construct and is portable; it can be quickly set
      up at any focused beamline with a tunable narrow bandwidth monochromator. The
      sample clearance is over 27 mm, providing compatibility with a variety of
      environment chambers. An overview is also given of the calibration and data
      processing procedures, which are implemented by a multiplatform user-friendly
      software package. Finally, representative measurements are presented. Background
      levels are below the level of the Kbeta(2, 5) valence emission, the weakest
      diagram line in the system, and photometric analysis of count rates finds that
      the instrument is performing at the theoretical limit.

PMID- 22380102
TI  - Cryogenic high-frequency readout and control platform for spin qubits.
AB  - We have developed a cryogenic platform for the control and readout of spin qubits
      that comprises a high density of dc and radio frequency sample interconnects
      based on a set of coupled printed circuit boards. The modular setup incorporates
      24 filtered dc lines, 14 control and readout lines with bandwidth from dc to
      above 6 GHz, and 2 microwave connections for excitation to 40 GHz. We report the
      performance of this platform, including signal integrity and crosstalk
      measurements and discuss design criteria for constructing sample interconnect
      technology needed for multi-qubit devices.

PMID- 22380103
TI  - Solid-state source of atomic oxygen for low-temperature oxidation processes:
      application to pulsed laser deposition of TiO2:N films.
AB  - An atomic oxygen (AO) source has been redesigned to coordinate with a pulsed
      laser deposition system and used to grow nitrogen-doped TiO(2) films by
      deposition of TiN and simultaneous irradiation of the substrate with AO. The AO
      source uses an incandescently heated thin tube of zirconia as an oxygen
      permeation media to generate pure AO of low kinetic energy. The emission flux is
      calibrated using a silver-coated quartz crystal microbalance. The thin shape of
      the probe and transverse emission geometry of this emission device allow the
      emission area to be positioned close to the substrate surface, enhancing the
      irradiation flux at the substrate. AO irradiation is crucial for formation of
      TiO(2) phases via oxidation of the deposited TiN laser plume, and is effective
      for decrease of the substrate temperature for crystallization of anatase phase to
      as low as around 200  degrees C.

PMID- 22380104
TI  - A 17 T horizontal field cryomagnet with rapid sample change designed for beamline
      use.
AB  - We describe a new 17 T cryomagnet for neutron, x-ray or optical experiments with
      rapid in situ sample change. Sample temperatures are controllable from below 2 K
      to 300 K in vacuum. Alternatively a room temperature bore insert can be used for
      experiments at the field center under atmospheric conditions. Some of the
      advantages of this system include very low background scattering due to the small
      amount of material in the beam path, rapid cooldown, and fast field ramping.
      Access is available in a +/-10 degrees -11 degrees  cone around the field
      direction on both sides.

PMID- 22380105
TI  - Pilot-scale cooling tower to evaluate corrosion, scaling, and biofouling control
      strategies for cooling system makeup water.
AB  - Pilot-scale cooling towers can be used to evaluate corrosion, scaling, and
      biofouling control strategies when using particular cooling system makeup water
      and particular operating conditions. To study the potential for using a number of
      different impaired waters as makeup water, a pilot-scale system capable of
      generating 27,000 kJ/h heat load and maintaining recirculating water flow with a
      Reynolds number of 1.92 * 10(4) was designed to study these critical processes
      under conditions that are similar to full-scale systems. The pilot-scale cooling
      tower was equipped with an automatic makeup water control system, automatic
      blowdown control system, semi-automatic biocide feeding system, and corrosion,
      scaling, and biofouling monitoring systems. Observed operational data revealed
      that the major operating parameters, including temperature change (6.6  degrees
      C), cycles of concentration (N = 4.6), water flow velocity (0.66 m/s), and air
      mass velocity (3660 kg/h m(2)), were controlled quite well for an extended period
      of time (up to 2 months). Overall, the performance of the pilot-scale cooling
      towers using treated municipal wastewater was shown to be suitable to study
      critical processes (corrosion, scaling, biofouling) and evaluate cooling water
      management strategies for makeup waters of complex quality.

PMID- 22380106
TI  - Active noise cancellation in a suspended interferometer.
AB  - We demonstrate feed-forward vibration isolation on a suspended Fabry-Perot
      interferometer using Wiener filtering and a variant of the common least mean
      square adaptive filter algorithm. We compare the experimental results with
      theoretical estimates of the cancellation efficiency. Using data from the recent
      Laser Interferometer Gravitational Wave Observatory (LIGO) Science Run, we also
      estimate the impact of this technique on full scale gravitational wave
      interferometers. In the future, we expect to use this technique also to remove
      acoustic, magnetic, and gravitational noise perturbations from the LIGO
      interferometers. This noise cancellation technique is simple enough to implement
      in standard laboratory environments and can be used to improve signal-to-noise
      ratio for a variety of high precision experiments.

PMID- 22380107
TI  - Thermal-structural analysis of electron gun with control grid.
AB  - Steady state thermal-structural analysis of electron guns is essential due to the
      requirement of high reliability in beam performance. Temperatures and
      displacements for all the components of an electron gun with a control grid are
      computed. Steady-state thermal analysis has been carried out for various cathode
      temperatures and various intercepted powers on the control grid to determine the
      temperature of the control grid. These results are verified experimentally based
      on measured results from an assembled electron gun. Structural analysis of the
      electron gun is used to evaluate the deformation of the inner electrodes under
      the hot condition. The results show that the thermal stress slightly changes the
      characteristics of the gun. The obtained thermal deformation data can be helpful
      to modify the design dimensions and assembly of an electron gun.

PMID- 22380108
TI  - Performance of a fast digital integrator in on-field magnetic measurements for
      particle accelerators.
AB  - The fast digital integrator has been conceived to face most demanding magnet test
      requirements with a resolution of 10 ppm, a signal-to-noise ratio of 105 dB at 20
      kHz, a time resolution of 50 ns, an offset of 10 ppm, and on-line processing. In
      this paper, the on-field achievements of the fast digital integrator are assessed
      by a specific measurement campaign at the European Organization for Nuclear
      Research (CERN). At first, the architecture and the metrological specifications
      of the instrument are reported. Then, the recent on-field achievements of (i) +/
      10 ppm of uncertainty in the measurement of the main field for superconducting
      magnets characterization, (ii) +/-0.02 % of field uncertainty in quality
      assessment of small-aperture permanent magnets, and (iii) +/-0.15 % of drift, in
      an excitation current measurement of 600 s under cryogenic conditions, are
      presented and discussed.

PMID- 22380109
TI  - Generalized four-point characterization method using capacitive and ohmic
      contacts.
AB  - In this paper, a four-point characterization method is developed for samples that
      have either capacitive or ohmic contacts. When capacitive contacts are used,
      capacitive current- and voltage-dividers result in a capacitive scaling factor
      not present in four-point measurements with only ohmic contacts. From a circuit
      equivalent of the complete measurement system, one can determine both the
      measurement frequency band and capacitive scaling factor for various four-point
      characterization configurations. This technique is first demonstrated with a
      discrete element four-point test device and then with a capacitively and
      ohmically contacted Hall bar sample over a wide frequency range (1 Hz-100 kHz)
      using lock-in measurement techniques. In all the cases, data fit well to a
      circuit simulation of the entire measurement system, and best results are
      achieved with large area capacitive contacts and a high input-impedance
      preamplifier stage. An undesirable asymmetry offset in the measurement signal is
      described which can arise due to asymmetric voltage contacts.

PMID- 22380110
TI  - Broadband microwave spectroscopy in Corbino geometry at 3He temperatures.
AB  - A broadband microwave spectrometer has been constructed to determine the complex
      conductivity of thin metal films at frequencies from 45 MHz to 20 GHz working in
      the temperature range from 0.45 K to 2 K (in a (3)He cryostat). The setup follows
      the Corbino approach: a vector network analyzer measures the complex reflection
      coefficient of a microwave signal hitting the sample as termination of a coaxial
      transmission line. As the calibration of the setup limits the achievable
      resolution, we discuss the sources of error hampering different types of
      calibration. Test measurements of the complex conductivity of a heavy-fermion
      material demonstrate the applicability of the calibration procedures.

PMID- 22380111
TI  - An explosively driven high-power microwave pulsed power system.
AB  - The increased popularity of high power microwave systems and the various sources
      to drive them is the motivation behind the work to be presented. A stand-alone,
      self-contained explosively driven high power microwave pulsed power system has
      been designed, built, and tested at Texas Tech University's Center for Pulsed
      Power and Power Electronics. The system integrates four different sub-units that
      are composed of a battery driven prime power source utilizing capacitive energy
      storage, a dual stage helical flux compression generator as the main energy
      amplification device, an integrated power conditioning system with inductive
      energy storage including a fast opening electro-explosive switch, and a triode
      reflex geometry virtual cathode oscillator as the microwave radiating source.
      This system has displayed a measured electrical source power level of over 5 GW
      and peak radiated microwaves of about 200 MW. It is contained within a 15 cm
      diameter housing and measures 2 m in length, giving a housing volume of slightly
      less than 39 l. The system and its sub-components have been extensively studied,
      both as integrated and individual units, to further expand on components behavior
      and operation physics. This report will serve as a detailed design overview of
      each of the four subcomponents and provide detailed analysis of the overall
      system performance and benchmarks.

PMID- 22380112
TI  - Application of length vernier in phase coincidence detection and precision
      frequency measurement.
AB  - For comparison of arbitrary frequency signals, the paper proposed two levels of
      length vernier based on the time-space relationship are used in three levels of
      phase coincidence detecting circuits to extract the phase coincidence information
      by proper logic calculation. The length/phase of each vernier is respectively
      corresponding to the accuracy and the resolution of detecting circuit. The time
      space relationship is based on high-stability, high-accuracy, and high-speed of
      signal transmission. The method is effective to reduce the fuzzy region in the
      phase coincidence information and reach a higher measuring precision.

PMID- 22380113
TI  - Effects of the transparent cathode on the performance of a relativistic magnetron
      with axial radiation.
AB  - Experimental investigation of the transparent cathode used in a relativistic
      magnetron with axial radiation is reported in this paper. The transparent cathode
      is composed of six separate stalks with the diameter of 6 mm. Under the working
      condition of 549 kV and ~0.38 T, the relativistic magnetron with the transparent
      cathode experimentally produces a 550 MW microwave. The radiation mode is TE(11)
      at the frequency of 2.35 GHz. The total efficiency is 16.7%. The variations of
      the relative positions between the separate stalks and the anode blocks can
      perform the maximum difference of 4 ns in microwave duration. Compared with the
      conventional solid cathode, the transparent cathode provides faster startup time
      of 12 ns, relatively wider pulse duration of 35% and relatively higher efficiency
      of 10.6%.

PMID- 22380114
TI  - A third-order complementary metal-oxide-semiconductor sigma-delta modulator
      operating between 4.2 K and 300 K.
AB  - This paper presents a third-order switched-capacitor sigma-delta modulator
      implemented in a standard 0.35-MUm CMOS process. It operates from 300 K down to
      4.2 K, achieving 70.8 dB signal-to-noise-plus-distortion ratio (SNDR) in a signal
      bandwidth of 5 kHz with a sampling frequency of 500 kHz at 300 K. The modulator
      utilizes an operational transconductance amplifier in its loop filter, whose
      architecture has been optimized in order to eliminate the cryogenic anomalies
      below the freeze-out temperature. At 4.2 K, the modulator achieves 67.7 dB SNDR
      consuming 21.17 MUA current from a 3.3 V supply.

PMID- 22380115
TI  - Development of high-voltage pulse-slicer unit with variable pulse duration for
      pulse radiolysis system.
AB  - A high-voltage pulse-slicer unit with variable pulse duration has been developed
      and integrated with a 7 MeV linear electron accelerator (LINAC) for pulse
      radiolysis investigation. The pulse-slicer unit provides switching voltage from 1
      kV to 10 kV with rise time better than 5 ns. Two MOSFET based 10 kV switches were
      configured in differential mode to get variable duration pulses. The high-voltage
      pulse has been applied to the deflecting plates of the LINAC for slicing of
      electron beam of 2 MUs duration. The duration of the electron beam has been
      varied from 30 ns to 2 MUs with the optimized pulse amplitude of 7 kV to get
      corresponding radiation doses from 6 Gy to 167 Gy.

PMID- 22380116
TI  - Quasi-omnidirectional electrical spectrometer for studying spin dynamics in
      magnetic tunnel junctions.
AB  - We report an omnidirectional electrical spectroscopy setup for studying the spin
      dynamics in a nanoscale magnet. It has a measureable solid angle range comprising
      about 50% of the total range and allows the magnetoresistance and spin-torque
      diode signal to be measured simultaneously at any angle to the magnetization.
      This setup can provide detailed information about the spin-wave resonance modes
      excited in a nanoscale magnet.

PMID- 22380117
TI  - Ultra-sensitive thermal conductance measurement of one-dimensional nanostructures
      enhanced by differential bridge.
AB  - Thermal conductivity of one-dimensional nanostructures, such as nanowires,
      nanotubes, and polymer chains, is of significant interest for understanding
      nanoscale thermal transport phenomena as well as for practical applications in
      nanoelectronics, energy conversion, and thermal management. Various techniques
      have been developed during the past decade for measuring this fundamental
      quantity at the individual nanostructure level. However, the sensitivity of these
      techniques is generally limited to 1 * 10(-9) W/K, which is inadequate for small
      diameter nanostructures that potentially possess thermal conductance ranging
      between 10(-11) and 10(-10) W/K. In this paper, we demonstrate an experimental
      technique which is capable of measuring thermal conductance of ~10(-11) W/K. The
      improved sensitivity is achieved by using an on-chip Wheatstone bridge circuit
      that overcomes several instrumentation issues. It provides a more effective
      method of characterizing the thermal properties of smaller and less conductive
      one-dimensional nanostructures. The best sensitivity experimentally achieved
      experienced a noise equivalent temperature below 0.5 mK and a minimum conductance
      measurement of 1 * 10(-11) W/K. Measuring the temperature fluctuation of both the
      four-point and bridge measurements over a 4 h time period shows a reduction in
      measured temperature fluctuation from 100 mK to 0.6 mK. Measurement of a 15 nm Ge
      nanowire and background conductance signal with no wire present demonstrates the
      increased sensitivity of the bridge method over the traditional four-point I-V
      measurement. This ultra-sensitive measurement platform allows for thermal
      measurements of materials at new size scales and will improve our understanding
      of thermal transport in nanoscale structures.

PMID- 22380118
TI  - Transducer for mechanical impedance testing over a wide frequency range through
      active feedback.
AB  - We describe a feedback-controlled active mechanical probe which can achieve a
      very low mechanical impedance, uniformly over a wide frequency range. The
      feedback produces a state of quasi-resonance which transforms the probe into a
      source of force used to excite an unknown load, resulting in a precise
      measurement of the real and imaginary components of the load impedance at any
      frequency. The instrument is applied to the determination of the mechanical
      impedance of a fingertip.

PMID- 22380119
TI  - High temperature Seebeck coefficient and resistance measurement system for
      thermoelectric materials in the thin disk geometry.
AB  - A versatile apparatus to measure the cross-plane Seebeck coefficient and the
      resistivity of bulk samples shaped as disks or thin plates, over a temperature
      range of 300 K-620 K with possible extension to higher temperatures, is
      presented. It is constructed from readily available equipment and instrumentation
      with parts that are easily manufactured. The Seebeck coefficient is measured over
      an average region of the sample under steady-state conditions. The sample
      resistance is measured using a four-point alternating current method and scaled
      to room temperature measurements with known geometry to calculate resistivity. A
      variety of sample shapes are supported. Most importantly, the support of the thin
      disk geometry allows for the very same samples to be used in a laser flash
      instrument. The design allows for rough vacuum, high vacuum, or purging with
      inert gases in the sample chamber. Measurements on thermoelectric ZnSb and a Ni
      reference material are presented.

PMID- 22380120
TI  - Compact cryogenic source of periodic hydrogen and argon droplet beams for
      relativistic laser-plasma generation.
AB  - We present a cryogenic source of periodic streams of micrometer-sized hydrogen
      and argon droplets as ideal mass-limited target systems for fundamental intense
      laser-driven plasma applications. The highly compact design combined with a high
      temporal and spatial droplet stability makes our injector ideally suited for
      experiments using state-of-the-art high-power lasers in which a precise
      synchronization between the laser pulses and the droplets is mandatory. We show
      this by irradiating argon droplets with multi-terawatt pulses.

PMID- 22380121
TI  - Non-contact thrust stand calibration method for repetitively pulsed electric
      thrusters.
AB  - A thrust stand calibration technique for use in testing repetitively pulsed
      electric thrusters for in-space propulsion has been developed and tested using a
      modified hanging pendulum thrust stand. In the implementation of this technique,
      current pulses are applied to a solenoid to produce a pulsed magnetic field that
      acts against a permanent magnet mounted to the thrust stand pendulum arm. The
      force on the magnet is applied in this non-contact manner, with the entire pulsed
      force transferred to the pendulum arm through a piezoelectric force transducer to
      provide a time-accurate force measurement. Modeling of the pendulum arm dynamics
      reveals that after an initial transient in thrust stand motion the quasi-steady
      average deflection of the thrust stand arm away from the unforced or "zero"
      position can be related to the average applied force through a simple linear
      Hooke's law relationship. Modeling demonstrates that this technique is
      universally applicable except when the pulsing period is increased to the point
      where it approaches the period of natural thrust stand motion. Calibration data
      were obtained using a modified hanging pendulum thrust stand previously used for
      steady-state thrust measurements. Data were obtained for varying impulse bit at
      constant pulse frequency and for varying pulse frequency. The two data sets
      exhibit excellent quantitative agreement with each other. The overall error on
      the linear regression fit used to determine the calibration coefficient was
      roughly 1%.

PMID- 22380122
TI  - Normalization schemes for ultrafast x-ray diffraction using a table-top laser
      driven plasma source.
AB  - We present an experimental setup of a laser-driven x-ray plasma source for
      femtosecond x-ray diffraction. Different normalization schemes accounting for x
      ray source intensity fluctuations are discussed in detail. We apply these schemes
      to measure the temporal evolution of Bragg peak intensities of perovskite
      superlattices after ultrafast laser excitation.

PMID- 22380123
TI  - Analysis of temporal jitter in a copper vapor laser system.
AB  - Temporal jitter in a magnetic pulse compression based copper vapor laser (CVL)
      system is analyzed by considering ripple present in the input dc power supply and
      ripple present in the magnetic core resetting power supply. It is shown that the
      jitter is a function of the ratio of operating voltage to the designed voltage,
      percentage ripple, and the total propagation delay of the magnetic pulse
      compression circuit. Experimental results from a CVL system operating at a
      repetition rate of 9 kHz are presented.

PMID- 22380124
TI  - An electrooptic probe to determine internal electric fields in a piezoelectric
      transformer.
AB  - A technique using the electrooptic effect to determine the output voltage of an
      optically clear LiNbO(3) piezoelectric transformer was developed and explored. A
      brief mathematical description of the solution is provided, as well as
      experimental data demonstrating a linear response under ac resonant operating
      conditions. A technique to calibrate the diagnostic was developed and is
      described. Finally, a sensitivity analysis of the electrooptic response to
      variations in angular alignment between the LiNbO(3) transformer and the laser
      probe are discussed.

PMID- 22380125
TI  - Quartz crystal microbalance based on passive frequency to voltage converter.
AB  - In dynamics of evaporation or drying of microdrops from a solid surface, a faster
      and precise quartz crystal microbalance (QCM) is needed. The fast QCM based on
      frequency to voltage converter is an attractive and powerful tool in the
      investigation of the dynamic regime of evaporation to translate the frequency
      shift in terms of a continuous voltage change. The frequency shift monitoring in
      fast QCM applications is a real challenge for electronic processing interface.
      Originally developed as a frequency shift processing interface, this novel
      passive frequency to voltage converter can produce faster, stable, and accurate
      results in regard to the QCM sensor behavior. In this article, the concept and
      circuit of passive frequency to voltage converter will be explained followed by
      static and dynamic characterization. Experimental results of microdrops
      evaporation will be given.

PMID- 22380126
TI  - Smith-chart diagnostics for multi-GHz time-domain-reflectometry dielectric
      spectroscopy.
AB  - A time-domain-reflectometry Smith-chart display is demonstrated to be a valuable
      diagnostic tool in a variety of situations in time-domain-reflectometry
      dielectric spectroscopy. A relative reflection coefficient is formed by dividing
      the Laplace transform of the reflected sample transient by the Laplace transform
      of the empty-sensor transient and displaying in the complex plane, with the
      approximate sensor admittance read from susceptance and conductance circles. The
      Smith chart provides, as a diagnostic tool, an initial estimate of the dielectric
      behavior in the multi-GHz range and a means of identifying artifacts in
      acquisition and Laplace transform, in a way which does not require multiple steps
      of calibration and is only one step removed from the direct transient. Results
      are presented for a simple 3.5-mm flat sensor immersed in various liquid media,
      showing variations in the Smith chart for typical variations in sample
      permittivity, loss, and conductivity. Results are matched to vector network
      analyzer (VNA) measurement over an identical frequency range, as well as to
      finite-element field simulation. Results are also presented for a 3.5-mm sensor
      with various terminating pin lengths, typically employed at low frequencies and
      low permittivity media to increase sensor capacitance. For an unshielded pin, the
      Smith chart detects reflections from sample boundaries and measures the
      effectiveness of shielding used to eliminate these reflections. For a shielded
      pin, it characterizes the effect of pin length on the susceptance variation and
      the onset of pin resonance at high frequencies and high-permittivity values. The
      effect of artifacts appearing in the Smith chart on the actual calibration is
      shown by tracking them through the calibration process to the final result.
      Results are also presented for a 9-mm flat termination used for concrete
      hydration monitoring, showing effects of transmission-line discontinuities within
      a terminating plug and the onset of waveguide-like modes in a surrounding shield,
      with results compared to VNA measurement.

PMID- 22380127
TI  - TetraMag: a compact magnetizing device based on eight rotating permanent magnets.
AB  - In this paper we describe a novel magnetizing device based on eight rotatable
      permanent magnets arranged in a quadrupolar configuration, which is termed the
      TetraMag. TetraMag creates stable and homogeneous magnetic fields at the sample
      position with a resolution of 0.02 mT tunable between -570 mT and +570 mT. The
      field direction is continuously rotatable between 0 degrees  and 360 degrees 
      within the sample plane, while the field strength is maintained. A simplified
      mathematical description of TetraMag is developed leading to magnetic field
      calculations which are in good agreement with the experimental results. This
      versatile device avoids electrical energy dissipation, cooling mechanisms, and
      hysteresis effects known from classical electromagnets. It is ultrahigh vacuum
      compatible and it offers a completely free optical path over 180 degrees  for
      magneto-optical experiments. It is suitable for scattering experiments with
      synchrotron radiation and neutrons and may be employed in a large class of
      magnetization experiments.

PMID- 22380128
TI  - Investigations of some aspects of the spray process in a single wire arc plasma
      spray system using high speed camera.
AB  - A high speed camera has been used to record and analyze the evolution as well as
      particle behavior in a single wire arc plasma spray torch. Commercially available
      systems (spray watch, DPV 2000, etc.) focus onto a small area in the spray jet.
      They are not designed for tracking a single particle from the torch to the
      substrate. Using high speed camera, individual particles were tracked and their
      velocities were measured at various distances from the spray torch. Particle
      velocity information at different distances from the nozzle of the torch is very
      important to decide correct substrate position for the good quality of coating.
      The analysis of the images has revealed the details of the process of arc
      attachment to wire, melting of the wire, and detachment of the molten mass from
      the tip. Images of the wire and the arc have been recorded for different wire
      feed rates, gas flow rates, and torch powers, to determine compatible wire feed
      rates. High speed imaging of particle trajectories has been used for particle
      velocity determination using time of flight method. It was observed that the
      ripple in the power supply of the torch leads to large variation of instantaneous
      power fed to the torch. This affects the velocity of the spray particles
      generated at different times within one cycle of the ripple. It is shown that the
      velocity of a spray particle depends on the instantaneous torch power at the time
      of its generation. This correlation was established by experimental evidence in
      this paper. Once the particles leave the plasma jet, their forward speeds were
      found to be more or less invariant beyond 40 mm up to 500 mm from the nozzle
      exit.

PMID- 22380129
TI  - Balloon-borne disposable radiometer for cloud detection.
AB  - A low cost, disposable instrument for measuring solar radiation during
      meteorological balloon flights through cloud layers is described. Using a
      photodiode detector and low thermal drift signal conditioning circuitry, the
      device showed less than 1% drift for temperatures varied from +20  degrees C to 
      35  degrees C. The angular response to radiation, which declined less rapidly
      than the cosine of the angle between the incident radiation and normal incidence,
      is used for cloud detection exploiting the motion of the platform. Oriented
      upwards, the natural motion imposed by the balloon allows cloud and clear air to
      be distinguished by the absence of radiation variability within cloud, where the
      diffuse radiation present is isotropic. The optical method employed by the solar
      radiation instrument has also been demonstrated to provide higher resolution
      measurements of cloud boundaries than relative humidity measurements alone.

PMID- 22380130
TI  - Environmental chamber for in situ dynamic control of temperature and relative
      humidity during x-ray scattering.
AB  - We have designed, constructed, and evaluated an environmental chamber that has in
      situ dynamic control of temperature (25 to 90  degrees C) and relative humidity
      (0% to 95%). The compact specimen chamber is designed for x-ray scattering in
      transmission with an escape angle of 2theta = +/-30 degrees . The specimen
      chamber is compatible with a completely evacuated system such as the Rigaku PSAXS
      system, in which the specimen chamber is placed inside a larger evacuated chamber
      (flight path). It is also compatible with x-ray systems consisting of evacuated
      flight tubes separated by small air gaps for sample placement. When attached to a
      linear motor (vertical displacement), the environmental chamber can access
      multiple sample positions. The temperature and relative humidity inside the
      specimen chamber are controlled by passing a mixture of dry and saturated gas
      through the chamber and by heating the chamber walls. Alternatively, the chamber
      can be used to control the gaseous environment without humidity. To illustrate
      the value of this apparatus, we have probed morphology transformations in
      Nafion((r)) membranes and a polymerized ionic liquid as a function of relative
      humidity in nitrogen.

PMID- 22380131
TI  - Design and analysis of a novel mechanical loading machine for dynamic in vivo
      axial loading.
AB  - This paper describes the construction of a loading machine for performing in
      vivo, dynamic mechanical loading of the rodent forearm. The loading machine
      utilizes a unique type of electromagnetic actuator with no mechanically resistive
      components (servotube), allowing highly accurate loads to be created. A
      regression analysis of the force created by the actuator with respect to the
      input voltage demonstrates high linear correlation (R(2) = 1). When the linear
      correlation is used to create dynamic loading waveforms in the frequency (0.5-10
      Hz) and load (1-50 N) range used for in vivo loading, less than 1% normalized
      root mean square error (NRMSE) is computed. Larger NRMSE is found at increased
      frequencies, with 5%-8% occurring at 40 Hz, and reasons are discussed. Amplifiers
      (strain gauge, linear voltage displacement transducer (LVDT), and load cell) are
      constructed, calibrated, and integrated, to allow well-resolved dynamic
      measurements to be recorded at each program cycle. Each of the amplifiers uses an
      active filter with cutoff frequency at the maximum in vivo loading frequencies
      (50 Hz) so that electronic noise generated by the servo drive and actuator are
      reduced. The LVDT and load cell amplifiers allow evaluation of stress-strain
      relationships to determine if in vivo bone damage is occurring. The strain gauge
      amplifier allows dynamic force to strain calibrations to occur for animals of
      different sex, age, and strain. Unique features are integrated into the loading
      system, including a weightless mode, which allows the limbs of anesthetized
      animals to be quickly positioned and removed. Although the device is constructed
      for in vivo axial bone loading, it can be used within constraints, as a general
      measurement instrument in a laboratory setting.

PMID- 22380132
TI  - Real-time measurement system for tracking birefringence, weight, thickness, and
      surface temperature during drying of solution cast coatings and films.
AB  - This paper describes the design and performance of a new instrument to track
      temporal changes in physical parameters during the drying behavior of solutions,
      as well as curing of monomers. This real-time instrument follows in-plane and out
      of-plane birefringence, weight, thickness, and surface temperature during the
      course of solidification of coatings and films through solvent evaporation and
      thermal or photocuring in a controlled atmosphere. It is specifically designed to
      simulate behavior of polymer solutions inside an industrial size, continuous roll
      to-roll solution casting line and other coating operations where resins are
      subjected to ultraviolet (UV) curing from monomer precursors. Controlled
      processing parameters include air speed, temperature, initial cast thickness, and
      solute concentration, while measured parameters are thickness, weight, film
      temperature, in-plane and out-of-plane birefringence. In this paper, we
      illustrate the utility of this instrument with solution cast and dried poly
      (amide-imide)/DMAc (Dimethylacetamide) solution, water based black paint, and
      organo-modified clay/NMP (N-Methylpyrrolidone) solution. In addition, the
      physical changes that take place during UV photo polymerization of a monomer are
      tracked. This instrument is designed to be generic and it can be used for
      tracking any drying/swelling/solidification systems including paper, foodstuffs
      such as; grains, milk as well as pharmaceutical thin paste and slurries.

PMID- 22380133
TI  - Power spectrum and Allan variance methods for calibrating single-molecule video
      tracking instruments.
AB  - Single-molecule manipulation instruments, such as optical traps and magnetic
      tweezers, frequently use video tracking to measure the position of a force
      generating probe. The instruments are calibrated by comparing the measured probe
      motion to a model of Brownian motion in a harmonic potential well; the results of
      calibration are estimates of the probe drag, alpha, and spring constant, kappa.
      Here, we present both time- and frequency-domain methods to accurately and
      precisely extract alpha and kappa from the probe trajectory. In the frequency
      domain, we discuss methods to estimate the power spectral density (PSD) from data
      (including windowing and blocking), and we derive an analytical formula for the
      PSD which accounts both for aliasing and the filtering intrinsic to video
      tracking. In the time domain, we focus on the Allan variance (AV): we present a
      theoretical equation for the AV relevant to typical single-molecule setups and
      discuss the optimal manner for computing the AV from experimental data using
      octave-sampled overlapping bins. We show that, when using maximum-likelihood
      methods to fit to the data, both the PSD and AV approaches can extract alpha and
      kappa in an unbiased and low-error manner, though the AV approach is simpler and
      more robust.

PMID- 22380134
TI  - Instrumentation of a compact random-access photostimulator based on acousto-optic
      deflectors.
AB  - Recently developed optogenetics provides a fast, non-invasive, and efficient
      method for cell activation. However, it is difficult for the optical stimulators
      used for optogenetics to realize selective multi-site fast activation. In this
      paper, we developed a random-access photostimulator based on a pair of
      perpendicularly oriented acousto-optic deflectors. Precise laser targeting in the
      x-y plane was verified, and the lateral spatial resolution of laser intensity
      after the objective was measured as ~1.38 MUm. Photostimulaton of ChETA
      expressing astrocytes induced reliable inward currents only if the laser beam was
      directed onto the targeted cell. In the ChR2-expresing neuron, multiple locations
      along two dendrites were stimulated, and spatiotemporal integration was observed
      in the soma with fast multi-site activation. These results demonstrated that this
      random-access photostimulator would be a powerful tool for selective multi-site
      fast activation. The compact and modular design of this photostimulator makes it
      easily integrated with different commercial microscopes, and thus widely
      popularized in many laboratories.

PMID- 22380135
TI  - Note: Absolute calibration of two DRZ phosphor screens using ultrashort electron
      bunch.
AB  - This article gives the absolute calibration of two types phosphor screens (DRZ)
      that were used to detect and characterize electron bunches driven by laser-plasma
      accelerator. The test was performed with picoseconds electron bunch at a radio
      frequency linear electron accelerator in Tsinghua University. The photons emitted
      from DRZ screens showed good linear responses to the charge of incident electron
      bunch and cosine angular distribution in space. An energy conversional efficiency
      of effective scintillant matter was also calculated.

PMID- 22380136
TI  - Note: Rotational compliance and instantaneous center of rotation in segmented and
      V-shaped notch hinges.
AB  - This note shows a technique for the calculation of rotational compliance
      (stiffness) and develops a generalized mathematical model for the virtual center
      of rotation position in concave, segmented, and V-shaped notch hinges using
      Chebyshev's polynomials. The calculational results are in a good agreement with
      experimental data and finite element model verified output with estimated
      differences of less than 10%. This agreement shows that our tractable model is a
      general one for rotational compliance and the evaluation of a virtual center of
      rotation position in any type of concave flexure notch hinges.

PMID- 22380137
TI  - Note: Self-sensing based on charge control improves the performance of active
      damping using piezoelements.
AB  - A piezoelectric element can be used separately as a sensor or an actuator. A self
      sensing strategy based on a charge driver can utilize a piezoelectric element as
      a sensor while actuating. The strategy was proven via experiments on a cantilever
      vibrator using a piezoelectric plate with both sensing and actuating functions.
      The amplitude of the vibration was actively damped by a factor exceeding 90%. The
      method can be used in numerous fields, including scanning probe microscopy,
      vibration suppression, and monitoring the health of structures.

PMID- 22380138
TI  - Note: A signal-to-noise ratio enhancement based on wafer light irradiation system
      for optical modulation spectroscopy measurement.
AB  - We have recently found that the magnitude of the photoreflectance (PR) signal
      DeltaR/R on silicon wafers depends on the duration of continuous probe or pump
      beams irradiation. This temporal behavior of the DeltaR/R signal is attributed to
      the defects related electronic states at the Si/ SiO(2) interface, which could be
      modified by the optical irradiation. Prior to the actual measurement, an optical
      irradiation of the silicon on insulator or ion implanted Si wafer can
      significantly enhance the signal-to-noise ratio of the PR intensity and,
      therefore, improve the goodness of fit. Such phenomena can be exclusively seen
      using a rapid detection system. A new design of the method is reported.

PMID- 22380139
TI  - Note: Laser-induced acoustic desorption/synchrotron vacuum ultraviolet
      photoionization mass spectrometry for analysis of fragile compounds and heavy
      oils.
AB  - In this work, we coupled synchrotron vacuum ultraviolet photoionization (SVUV PI)
      method with the laser-induced acoustic desorption (LIAD) technique for mass
      spectrometric analysis. The LIAD technique is a "soft" desorption method, which
      could avoid the degradation of analytes during desorption process. Meanwhile,
      SVUV PI is an efficient "soft" ionization source. The new combination of the
      "soft" desorption technique and "soft" photoionization method is well suitable to
      reduce the difficulty for interpreting the mass spectra of the fragile compounds
      and heavy oils.

PMID- 22380140
TI  - Note: A high dynamic range, linear response transimpedance amplifier.
AB  - We have built a high dynamic range (nine decade) transimpedance amplifier with a
      linear response. The amplifier uses junction-gate field effect transistors
      (JFETs) to switch between three different resistors in the feedback of a low
      input bias current operational amplifier. This allows for the creation of
      multiple outputs, each with a linear response and a different transimpedance
      gain. The overall bandwidth of the transimpedance amplifier is set by the
      bandwidth of the most sensitive range. For our application, we demonstrate a
      three-stage amplifier with transimpedance gains of approximately 10(9)Omega, 3 *
      10(7)Omega, and 10(4)Omega with a bandwidth of 100 Hz.

PMID- 22380141
TI  - Note: Ultrasonic liquid flow meter for small pipes.
AB  - An ultrasonic flow meter for small pipes is presented. For metal pipe diameter
      smaller than 10 mm, clamp-on ultrasonic contrapropagation flow meters may
      encounter difficulties if cross talk or the short acoustic path contributes to
      large uncertainty in transit time measurement. Axial inline flow meters can avoid
      these problems, but they may introduce other problems if the transducer port is
      not properly positioned. Three types of pipe connecting tees are compared using
      the computational fluid dynamics (CFD) method. CFD shows the 45 degrees  tee has
      more uniform velocity distribution over the measuring section. A prototype flow
      meter using the 45 degrees  tee was designed and tested. The zero flow experiment
      shows the flow meter has a maximum of 0.002 m/s shift over 24 h. The flow meter
      is calibrated by only 1 meter factor. After calibration, inaccuracy lower than
      0.1% of reading was achieved in the laboratory, for a measuring range from 15 to
      150 g/s (0.29 to 2.99 m/s; Re = 2688 to 26,876).

PMID- 22380142
TI  - Note: Studies on x-ray production in electron cyclotron resonance x-ray source
      based on ridged cylindrical cavity.
AB  - A ridged cylindrical cavity has been designed using MICROWAVE STUDIO programme
      and it is used in the electron cyclotron resonance (ECR) x-ray source. The
      experimental parameters of the source are optimized for maximizing the x-ray
      output, and an x-ray dose rate of ~1000 MUSv/h was observed at 20 cm from the
      port, for 500 W of microwave power without using any target. With the molybdenum
      target located at optimum position of the ridged cavity, the dose rate is found
      to be increased only by 10%. In order to understand the experimental observation,
      the electric field pattern of the cavity with the target placed at various radial
      distances is studied. In this note, the experimental and theoretical studies on
      ECR x-ray source using the ridged cylindrical cavity are presented.

PMID- 22380143
TI  - Note: Frequency-conversion photonic Doppler velocimetry with an inverted
      circulator.
AB  - Photonic Doppler velocimetry (PDV) is a fiber-based interferometer used in
      dynamic compression research. Conventional PDV systems are simple to construct
      but do not perform well in all measurement conditions, while universal PDV
      systems that support many different configurations are complex and expensive. A
      simpler approach is the use of external, inverted circulators which can be added
      and removed in a modular fashion. This technique permits frequency-conversion
      measurements with a conventional PDV system. Using a correction to remove
      baseline effects, frequency conversion systems can resolve low velocity
      transients that conventional PDV cannot.

PMID- 22380148
TI  - Concept for a fourth generation electron cyclotron resonance ion source.
AB  - A fourth generation electron cyclotron resonance ion source with an operating
      frequency between 40 and 56 GHz has the potential to quadruple the heavy-ion beam
      currents and provide a cost effective upgrade path for heavy ion drivers in use
      or in the planning stage at radioactive beam facilities. Design studies show it
      is feasible to produce the required magnetic fields in the plasma chamber, 7 T
      axially and 4 T in the radial direction with a magnetic structure using
      commercially available Nb(3)Sn superconducting materials. In this paper we
      describe the design of such a magnet structure including a 3D analysis of the
      Lorentz forces generated by the magnetic fields and the necessary clamping
      structure to stabilize the conductor against these forces.

PMID- 22380149
TI  - A new structure of superconducting magnetic system for 50 GHz operations
      (invited).
AB  - High field and high frequency have been leading the development of electron
      cyclotron resonance ion sources (ECRISs) in the past decade as demonstrated by
      the achieved great performance. The present superconducting magnet structures
      built with NbTi wires have reached an axial field of 3.5-4.0 T and a radial field
      of 2.0 T for operating frequency up to 28 GHz. Further increase of the magnetic
      field strength will require higher current superconductor, i.e., Nb(3)Sn wires.
      This paper will present the features of a new superconducting magnet structure
      and review of the existing structures. Using NbTi wires, the new magnet structure
      could be able to produce maximum fields of 7.0 T on axis and radial field of 3.7
      T at a hexagonal plasma chamber wall for ECRIS operations up to 50 GHz. If this
      new magnet can be built with Nb(3)Sn wires, much higher fields can be expected.

PMID- 22380150
TI  - Effect of pulse-modulated microwaves on fullerene ion production with electron
      cyclotron resonance ion source.
AB  - Fullerene plasmas generated by pulse-modulated microwaves have been investigated
      under typical conditions at the Bio-Nano electron cyclotron resonance ion source.
      The effect of the pulse modulation is distinct from that of simply structured
      gases, and then the density of the fullerene plasmas increased as decreasing the
      duty ratio. The density for a pulse width of 10 MUs at the period of 100 MUs is
      1.34 times higher than that for CW mode. We have studied the responses of
      fullerene and argon plasmas to pulsed microwaves. After the turnoff of microwave
      power, fullerene plasmas lasted ~30 times longer than argon plasmas.

PMID- 22380151
TI  - Operation of the CAPRICE electron cyclotron resonance ion source applying
      frequency tuning and double frequency heating.
AB  - The properties of the electromagnetic waves heating the electrons of the ECR ion
      sources (ECRIS) plasma affect the features of the extracted ion beams such as the
      emittance, the shape, and the current, in particular for higher charge states.
      The electron heating methods such as the frequency tuning effect and the double
      frequency heating are widely used for enhancing the performances of ECRIS or even
      for the routine operation during the beam production. In order to better
      investigate these effects the CAPRICE ECRIS has been operated using these
      techniques. The ion beam properties for highly charged ions have been measured
      with beam diagnostic tools. The reason of the observed variations of this
      performance can be related to the different electromagnetic field patterns, which
      are changing inside the plasma chamber when the frequency is varying.

PMID- 22380152
TI  - Characterization of the versatile ion source and possible applications as
      injector for future projects.
AB  - The versatile ion source (VIS) is an off-resonance microwave discharge ion source
      which generates a slightly overdense plasma (n(e) ~ 10(17) cm(-3)) operating at
      2.45 GHz and producing more than 50 mA of proton beams. A detailed
      characterization of the source, by operating between 60 and 75 kV, in terms of
      emittance, current extracted and proton fraction is reported below. Moreover,
      passive techniques (alumina coating of the plasma chamber walls, BN disks at the
      injection and extraction endplates) have been used to improve the performance of
      the source, increasing the electron density for a more efficient ionization. The
      know-how achieved with the VIS source may be useful for the different project,
      particularly for the European spallation source.

PMID- 22380153
TI  - Electron cyclotron resonance ion source plasma chamber studies using a network
      analyzer as a loaded cavity probe.
AB  - A method and first results utilizing a network analyzer as a loaded cavity probe
      to study the resonance properties of a plasma filled electron cyclotron resonance
      ion source (ECRIS) plasma chamber are presented. The loaded cavity measurements
      have been performed using a dual port technique, in which two separate waveguides
      were used simultaneously. One port was used to ignite and sustain the plasma with
      a microwave source operating around 11 GHz and the other was used to probe the
      cavity properties with the network analyzer using a frequency range around 14
      GHz. The first results obtained with the JYFL 14 GHz ECRIS demonstrate that the
      presence of plasma has significant effects on the resonance properties of the
      cavity. With plasma the frequency dependent behavior is strongly damped and this
      trend strengthens with increasing microwave power.

PMID- 22380154
TI  - Advanced light ion source extraction system for a new electron cyclotron
      resonance ion source geometry at Saclay.
AB  - One of the main goal of intense light ion injector projects such as IPHI, IFMIF,
      or SPIRAL2, is to produce high current beams while keeping transverse emittance
      as low as possible. To prevent emittance growth induced in a dual solenoid low
      energy transfer line, its length has to be minimized. This can be performed with
      the advanced light ion source extraction system concept that we are developing: a
      new ECR 2.45 GHz type ion source based on the use of an additional low energy
      beam transport (LEBT) short length solenoid close to the extraction aperture to
      create the resonance in the plasma chamber. The geometry of the source has been
      considerably modified to allow easy maintenance of each component and to save
      space in front of the extraction. The source aims to be very flexible and to be
      able to extract high current ion beams at energy up to 100 kV. A specific
      experimental setup for this source is under installation on the BETSI test bench,
      to compare its performances with sources developed up to now in the laboratory,
      such as SILHI, IFMIF, or SPIRAL2 ECR sources. This original extraction source
      concept is presented, as well as electromagnetic simulations with OPERA-2D code.
      Ion beam extraction in space charge compensation regime with AXCEL, and beam
      dynamics simulation with SOLMAXP codes show the beam quality improvement at the
      end of the LEBT.

PMID- 22380155
TI  - Results of RIKEN superconducting electron cyclotron resonance ion source with 28
      GHz.
AB  - We measured the beam intensity of highly charged heavy ions and x-ray heat load
      for RIKEN superconducting electron cyclotron resonance ion source with 28 GHz
      microwaves under the various conditions. The beam intensity of Xe(20+) became
      maximum at B(min) ~ 0.65 T, which was ~65% of the magnetic field strength of
      electron cyclotron resonance (B(ECR)) for 28 GHz microwaves. We observed that the
      heat load of x-ray increased with decreasing gas pressure and field gradient at
      resonance zone. It seems that the beam intensity of highly charged heavy ions
      with 28 GHz is higher than that with 18 GHz at same RF power.

PMID- 22380156
TI  - Generation of high charge state metal ion beams by electron cyclotron resonance
      heating of vacuum arc plasma in cusp trap.
AB  - A method for generating high charge state heavy metal ion beams based on high
      power microwave heating of vacuum arc plasma confined in a magnetic trap under
      electron cyclotron resonance conditions has been developed. A feature of the work
      described here is the use of a cusp magnetic field with inherent "minimum-B"
      structure as the confinement geometry, as opposed to a simple mirror device as we
      have reported on previously. The cusp configuration has been successfully used
      for microwave heating of gas discharge plasma and extraction from the plasma of
      highly charged, high current, gaseous ion beams. Now we use the trap for heavy
      metal ion beam generation. Two different approaches were used for injecting the
      vacuum arc metal plasma into the trap--axial injection from a miniature arc
      source located on-axis near the microwave window, and radial injection from
      sources mounted radially at the midplane of the trap. Here, we describe
      preliminary results of heating vacuum arc plasma in a cusp magnetic trap by
      pulsed (400 MUs) high power (up to 100 kW) microwave radiation at 37.5 GHz for
      the generation of highly charged heavy metal ion beams.

PMID- 22380157
TI  - Dependence of ion beam current on position of mobile plate tuner in multi
      frequencies microwaves electron cyclotron resonance ion source.
AB  - We are constructing a tandem-type electron cyclotron resonance ion source
      (ECRIS). The first stage of this can supply 2.45 GHz and 11-13 GHz microwaves to
      plasma chamber individually and simultaneously. We optimize the beam current
      I(FC) by the mobile plate tuner. The I(FC) is affected by the position of the
      mobile plate tuner in the chamber as like a circular cavity resonator. We aim to
      clarify the relation between the I(FC) and the ion saturation current in the
      ECRIS against the position of the mobile plate tuner. We obtained the result that
      the variation of the plasma density contributes largely to the variation of the
      I(FC) when we change the position of the mobile plate tuner.

PMID- 22380158
TI  - Recent progress on the superconducting ion source VENUS.
AB  - The 28 GHz Ion Source VENUS (versatile ECR for nuclear science) is back in
      operation after the superconducting sextupole leads were repaired and a fourth
      cryocooler was added. VENUS serves as an R&D device to explore the limits of
      electron cyclotron resonance source performance at 28 GHz with its 10 kW gryotron
      and optimum magnetic fields and as an ion source to increase the capabilities of
      the 88-Inch Cyclotron both for nuclear physics research and applications. The
      development and testing of ovens and sputtering techniques cover a wide range of
      applications. Recent experiments on bismuth demonstrated stable operation at 300
      eMUA of Bi(31+), which is in the intensity range of interest for high performance
      heavy-ion drivers such as FRIB (Facility for Rare Isotope Beams). In addition,
      the space radiation effects testing program at the cyclotron relies on the
      production of a cocktail beam with many species produced simultaneously in the
      ion source and this can be done with a combination of gases, sputter probes, and
      an oven. These capabilities are being developed with VENUS by adding a low
      temperature oven, sputter probes, as well as studying the RF coupling into the
      source.

PMID- 22380159
TI  - The electron cyclotron resonance ion source with arc-shaped coils concept
      (invited).
AB  - The main limitation to further improve the performance of ECR ion sources is set
      by the magnet technology related to the multipole magnet field used for the
      closed minimum-B structure. The JYFL ion source group has sought different
      approaches to improve the strength of the minimum-B structure required for the
      production of highly charged ion beams. It was found out that such a
      configuration can be realized with arc shaped coils. The first prototype,
      electron cyclotron resonance ion source with arc-shaped coils (ARC-ECRIS), was
      constructed and tested at JYFL in 2006. It was confirmed that such an ion source
      can be used for the production of highly charged ion beams. Regardless of several
      cost-driven compromises such as extraction mirror ratio of 1.05-1.2, microwave
      frequency of 6.4 GHz, and beam line with limited capacity, Ar(4+) beam intensity
      of up to 2 MUA was measured. Subsequent design study has shown that the ARC-ECRIS
      operating at the microwave frequency above 40 GHz could be constructed. This
      specific design would be based on NbTi-wires and it fulfills the experimental
      magnetic field scaling laws. In this article, the ARC-ECRIS concept and its
      potential applications will be described.

PMID- 22380160
TI  - Molecular and negative ion production by a standard electron cyclotron resonance
      ion source.
AB  - Molecular and negative ion beams, usually produced in special ion sources, play
      an increasingly important role in fundamental and applied atomic physics. The
      ATOMKI-ECRIS is a standard ECR ion source, designed to provide highly charged ion
      (HCI) plasmas and beams. In the present work, H(-), O(-), OH(-), O(2)(-), C(-),
      C(60)(-) negative ions and H(2)(+), H(3)(+), OH(+), H(2)O(+), H(3)O(+), O(2)(+)
      positive molecular ions were generated in this HCI-ECRIS. Without any major
      modification in the source and without any commonly applied tricks (such as usage
      of cesium or magnetic filter), negative ion beams of several MUA and positive
      molecular ion beams in the mA range were successfully obtained.

PMID- 22380161
TI  - The effect of gas mixing and biased disc voltage on the preglow transient of
      electron cyclotron resonance ion source.
AB  - The effect of gas mixing and biased disc voltage on the preglow of electron
      cyclotron resonance ion source plasma has been studied with the AECR-U type 14
      GHz ion source. It was found that gas mixing has a significant effect on the
      preglow. The extracted transient beam currents and efficiency of the heavier
      species increase, while the currents and efficiency of the lighter species
      decrease when gas mixing is applied. The effect of the biased disc was found to
      be pronounced in continuous operation mode in comparison to preglow. The data
      provide information on the time scales of the plasma processes explaining the
      effects of gas mixing and biased disc. The results also have implications on
      production of radioactive ion beams in preglow mode for the proposed Beta Beam
      neutrino factory.

PMID- 22380162
TI  - Development of compact linear accelerator in KBSI.
AB  - The compact linear accelerator using a 28 GHz ECRIS is under construction in
      KBSI, South Korea. The main capability of this facility is the production of fast
      neurons for the neutron radiography. The designing of a superconducting magnet,
      microwave transmission system, beam extraction, and plasma chamber of ECRIS were
      finished. The nominal axial design fields of the magnets are 3.6 T at injection
      and 2.2 T at extraction; the nominal radial design field strength at the plasma
      chamber wall is 2.1 T. We already installed 10 kW, 28 GHz gyrotron, and tested a
      microwave power from gyrotron using a dummy load. The current status will be
      discussed in this paper.

PMID- 22380163
TI  - Light ion source for proton/deuteron production at CEA Saclay for the Spiral2
      project.
AB  - The production of rare radioactive ion beam (RIB) far from the valley of
      stability is one of the final purposes of the Spiral2 facility in Caen. The RIB
      will be produced by impinging a deuteron beam onto a carbon sample to produce a
      high neutron flux, which will interact with a uranium target. The primary
      deuteron beam is produced by an ion source based on ECR plasma generation. The
      deuteron source and the low energy beam transport (LEBT) has been assembled and
      tested at CEA Saclay. Diagnostics from other laboratories were implemented on the
      LEBT in order to characterize the deuteron beam produced and compare it to the
      initial simulations. The ion source has been based on a SILHI-type source, which
      has demonstrated good performances in pulsed and continuous mode, and also a very
      good reliability on long term operation. The 5 mA of deuteron beam required at
      the RFQ entrance is extracted from the plasma source at the energy of 40 kV.
      After a brief description of the experimental set-up, this article reports on the
      first beam characterization experiments.

PMID- 22380164
TI  - Profiles of ion beams and plasma parameters on a multi-frequencies microwaves
      large bore electron cyclotron resonance ion source with permanent magnets.
AB  - In order to contribute to various applications of plasma and beams based on an
      electron cyclotron resonance, a new concept on magnetic field with all magnets on
      plasma production and confinement has been proposed with enhanced efficiency for
      broad and dense ion beam. The magnetic field configuration consists of a pair of
      comb-shaped magnet surrounding plasma chamber cylindrically. Resonance zones
      corresponding for 2.45 GHz and 11-13 GHz frequencies are positioned at spatially
      different positions. We launch simultaneously multiplex frequencies microwaves
      operated individually, try to control profiles of the plasma parameters and the
      extracted ion beams, and to measure them in detail.

PMID- 22380165
TI  - Influence of the shear flow on electron cyclotron resonance plasma confinement in
      an axisymmetric magnetic mirror trap of the electron cyclotron resonance ion
      source.
AB  - Influence of shear flows of the dense plasma created under conditions of the
      electron cyclotron resonance (ECR) gas breakdown on the plasma confinement in the
      axisymmetric mirror trap ("vortex" confinement) was studied experimentally and
      theoretically. A limiter with bias potential was set inside the mirror trap for
      plasma rotation. The limiter construction and the optimal value of the potential
      were chosen according to the results of the preliminary theoretical analysis.
      This method of "vortex" confinement realization in an axisymmetric mirror trap
      for non-equilibrium heavy-ion plasmas seems to be promising for creation of ECR
      multicharged ion sources with high magnetic fields, more than 1 T.

PMID- 22380166
TI  - Design and investigations of the superconducting magnet system for the
      multipurpose superconducting electron cyclotron resonance ion source.
AB  - The production of intense beams of heavy ions with electron cyclotron resonance
      ion sources (ECRIS) is an important request at many accelerators. According to
      the ECR condition and considering semi-empirical scaling laws, it is essential to
      increase the microwave frequency together with the magnetic flux density of the
      ECRIS magnet system. A useful frequency of 28 GHz, therefore, requires magnetic
      flux densities above 2.2 T implying the use of superconducting magnets. A
      cooperation of European institutions initiated a project to build a multipurpose
      superconducting ECRIS (MS-ECRIS) in order to achieve an increase of the
      performances in the order of a factor of ten. After a first design of the
      superconducting magnet system for the MS-ECRIS, the respective cold testing of
      the built magnet system reveals a lack of mechanical performance due to the
      strong interaction of the magnetic field of the three solenoids with the
      sextupole field and the magnetization of the magnetic iron collar. Comprehensive
      structural analysis, magnetic field calculations, and calculations of the force
      pattern confirm thereafter these strong interactions, especially of the iron
      collar with the solenoidal fields. The investigations on the structural analysis
      as well as suggestions for a possible mechanical design solution are given.

PMID- 22380167
TI  - Performance and operation of advanced superconducting electron cyclotron
      resonance ion source SECRAL at 24 GHz.
AB  - SECRAL (superconducting ECR ion source with advanced design in Lanzhou) ion
      source has been in routine operation for Heavy Ion Research Facility in Lanzhou
      (HIRFL) accelerator complex since May 2007. To further enhance the SECRAL
      performance in order to satisfy the increasing demand for intensive highly
      charged ion beams, 3-5 kW high power 24 GHz single frequency and 24 GHz +18 GHz
      double frequency with an aluminum plasma chamber were tested, and some exciting
      results were produced with quite a few new record highly charged ion beam
      intensities, such as (129)Xe(35+) of 64 eMUA, (129)Xe(42+) of 3 eMUA,
      (209)Bi(41+) of 50 eMUA, (209)Bi(50+) of 4.3 eMUA and (209)Bi(54+) of 0.2 eMUA.
      In most cases SECRAL is operated at 18 GHz to deliver highly charged heavy ion
      beams for the HIRFL accelerator, only for those very high charge states and very
      heavy ion beams such as (209)Bi(36+) and (209)Bi(41+), SECRAL has been operated
      at 24 GHz. The total operation beam time provided by SECRAL up to July 2011 has
      exceeded 7720 hours. In this paper, the latest performance, development, and
      operation status of SECRAL ion source are presented. The latest results and
      reliable long-term operation for the HIRFL accelerator have demonstrated that
      SECRAL performance for production of highly charged heavy ion beams remains
      improving at higher RF power with optimized tuning.

PMID- 22380168
TI  - Reliability test of an electron cyclotron resonance ion source for accelerator
      driven sub-critical system.
AB  - The reliability test of an electron cyclotron resonance ion source developed for
      accelerator driven sub-critical system is carried out in China Institute of
      Atomic Energy. A unique technique to improve the reliability is adopted. The
      source is operated for more than 200 h at 75 keV, 100 mA extracted hydrogen
      current, while 2 beam trips are recorded in the period, and uninterrupted
      operation time is about 150 h. The experimental result is described.

PMID- 22380169
TI  - Design of a compact electron cyclotron resonance ion source for medium charge
      state light ions.
AB  - At the Australian Nuclear Science and Technology Organization we are developing a
      new isotope ratio mass spectrometer based on the measurement of multiple charge
      state ions. We have carried out a review of our existing ECR ion source and
      identified a number of design flaws. For the new instrument, we are producing a
      new ECR source and have refined the design, in particular by using 3D simulations
      to improve the magnetic confinement field and by a combination of simulations and
      experiments to improve the design of the microwave coupling.

PMID- 22380170
TI  - First commissioning results with the Grenoble test electron cyclotron resonance
      ion source at iThemba LABS.
AB  - iThemba Laboratory for Accelerator Based Science (iThemba LABS) is a multi
      disciplinary accelerator facility. One of its main activities is the operation of
      a separated-sector cyclotron with a K-value of 200, which provides beams of
      various ion species. These beams are used for fundamental nuclear physics
      research in the intermediate energy region, radioisotope production, and medical
      physics applications. Due to the requirements of nuclear physics for new ion
      species and higher energies, the decision was made to install a copy of the so
      called Grenoble test source (GTS) at iThemba LABS. In this paper, we will report
      on the experimental setup and the first results obtained with the GTS2 at iThemba
      LABS.

PMID- 22380171
TI  - Electron cyclotron resonance plasma production by using pulse mode microwaves and
      dependences of ion beam current and plasma parameters on the pulse condition.
AB  - We measure the ion beam current and the plasma parameters by using the pulse mode
      microwave operation in the first stage of a tandem type ECRIS. The time averaged
      extracted ion beam current in the pulse mode operation is larger than that of the
      cw mode operation with the same averaged microwave power. The electron density
      n(e) in the pulse mode is higher and the electron temperature T(e) is lower than
      those of the cw mode operation. These plasma parameters are considered to cause
      in the increase of the ion beam current and are suitable to produce molecular or
      cluster ions.

PMID- 22380172
TI  - Multicharged ion source based on Penning-type discharge with electron cyclotron
      resonance heating by millimeter waves.
AB  - We suggest a Penning-type discharge as a trigger discharge for fast development
      of pulsed electron cyclotron resonance plasma. The Penning-type discharge glows
      at a low pressure as needed. Gyrotron radiation (75 GHz, 200 kW, 1 ms) was used
      for plasma heating. Fully striped helium ions were demonstrated, average charge
      of ions in the plasma was ~ 2. Experiment and calculations show that high charge
      states of heavier gases require lower initial pressure and longer development
      time. Only moderate charge states are achievable in this pulsed scheme.

PMID- 22380173
TI  - Design and fabrication of a superconducting magnet for an 18 GHz electron
      cyclotron resonance ion/photon source NFRI-ECRIPS.
AB  - A superconducting magnet was designed and fabricated for an 18 GHz ECR ion/photon
      source, which will be installed at National Fusion Research Institute (NFRI) in
      South Korea. The magnetic system consists of a set of four superconducting coils
      for axial mirror field and 36 pieces of permanent magnets for hexapolar field.
      The superconducting coils with a cryocooler (1.5 W @ 4.2 K) allow one to reach
      peak mirror fields of 2.2 T in the injection and those of 1.5 T in the extraction
      regions on the source axis, and the resultant hexapolar field gives 1.35 T on the
      plasma chamber wall. The unbalanced magnetic force between the coils and
      surrounding yoke has been minimized to 16 ton by a coil arrangement and their
      electrical connection, and then was successfully suspended by 12 strong thermal
      insulating supports made of large numbers of carbon fibers. In order to block
      radiative thermal losses, multilayer thermal insulations are covered on the coil
      windings as well as 40-K aluminum thermal shield. Also new schemes of quench
      detection and safety system (coil divisions, quench detection coils, and heaters)
      were employed. For impregnation of the windings a special epoxy has been selected
      and treated to have a higher breaking strength and a higher thermal conductivity,
      which enables the superconductors to be uniformly and rapidly cooled down or
      heated during a quench.

PMID- 22380174
TI  - Improvement of efficiency and temperature control of induction heating vapor
      source on electron cyclotron resonance ion source.
AB  - An electron cyclotron resonance ion source (ECRIS) is used to generate
      multicharged ions for many kinds of the fields. We have developed an evaporator
      by using induction heating method that can generate pure vapor from solid state
      materials in ECRIS. We develop the new matching and protecting circuit by which
      we can precisely control the temperature of the induction heating evaporator. We
      can control the temperature within +/-15  degrees C around 1400  degrees C under
      the operation pressure about 10(-4) Pa. We are able to use this evaporator for
      experiment of synthesizing process to need pure vapor under enough low pressure,
      e.g., experiment of generation of endohedral Fe-fullerene at the ECRIS.

PMID- 22380175
TI  - Development of DRAGON electron cyclotron resonance ion source at Institute of
      Modern Physics.
AB  - A new room temperature electron cyclotron resonance (ECR) ion source, DRAGON, is
      under construction at IMP. DRAGON is designed to operate at microwaves of
      frequencies of 14.5-18 GHz. Its axial solenoid coils are cooled with evaporative
      medium to provide an axial magnetic mirror field of 2.5 T at the injection and
      1.4 T at the extraction, respectively. In comparison to other conventional room
      temperature ECR ion sources, DRAGON has so far the largest bore plasma chamber of
      inner diameter of 126 mm with maximum radial fields of 1.4-1.5 T produced by a
      non-Halbach permanent sextupole magnet.

PMID- 22380176
TI  - A 2.45 GHz electron cyclotron resonance proton ion source and a dual-lens low
      energy beam transport.
AB  - The structure and preliminary commissioning results of a new 2.45 GHz ECR proton
      ion source and a dual-lens low energy beam transport (LEBT) system are presented
      in this paper. The main magnetic field of the ion source is provided by a set of
      permanent magnets with two small electro-solenoid magnets at the injection and
      the extraction to fine tune the magnetic field for better microwave coupling. A
      50 keV pulsed proton beam extracted by a three-electrode mechanism passes through
      the LEBT system of length of 1183 mm. This LEBT consists of a diagnosis chamber,
      two Glaser lenses, two steering magnets, and a final beam defining cone. A set of
      inner permanent magnetic rings is embedded in each of the two Glaser lenses to
      produce a flatter axial-field to reduce the lens aberrations.

PMID- 22380177
TI  - A 3D Monte Carlo code for the modeling of plasma dynamics and beam formation
      mechanism in electron cyclotron resonance ion sources.
AB  - The code here presented is the first part of a Monte Carlo (MC) self-consistent
      3D plasma simulator. It is yet able to solve the equation of motion for thousands
      of independent charged particles. The procedure allows to understand the
      consequences of each phenomenon introduced in the evolution steps of the code. MC
      random selection of starting parameters is used for each particles; the
      environmental conditions enclosed in the simulation are ECRIS magnetic field,
      resonant electromagnetic wave, initial plasma density distribution and MC
      calculation of Spitzer collision. The results of the first simulations explain
      some typical effects as the hollow beam formation and the main plasma
      deconfinement mechanism.

PMID- 22380178
TI  - The influence of the extraction voltage on the energetic electron population of
      an electron cyclotron resonance ion source plasma.
AB  - An influence of the extraction voltage on the high energy slope of bremsstrahlung
      radiation spectra has been reported in ECRIS experiments, which is not well
      understood so far. In order to provide more detailed data on this effect, we have
      measured bremsstrahlung radiation spectra accompanying especially the evolution
      of highly charge ions (i.e., by monitoring the Ar(14+) charge state) as the
      extraction voltage is changed from 0 to 20 kV, in dedicated experiments at the
      Frankfurt 14 GHz-ECRIS.

PMID- 22380179
TI  - Status of ion sources at National Institute of Radiological Sciences.
AB  - The National Institute of Radiological Sciences (NIRS) maintains various ion
      accelerators in order to study the effects of radiation of the human body and
      medical uses of radiation. Two electrostatic tandem accelerators and three
      cyclotrons delivered by commercial companies have offered various life science
      tools; these include proton-induced x-ray emission analysis (PIXE), micro beam
      irradiation, neutron exposure, and radioisotope tracers and probes. A
      duoplasmatron, a multicusp ion source, a penning ion source (PIG), and an
      electron cyclotron resonance ion source (ECRIS) are in operation for these
      purposes. The Heavy-Ion Medical Accelerator in Chiba (HIMAC) is an accelerator
      complex for heavy-ion radiotherapy, fully developed by NIRS. HIMAC is utilized
      not only for daily treatment with the carbon beam but also for fundamental
      experiments. Several ECRISs and a PIG at HIMAC satisfy various research and
      clinical requirements.

PMID- 22380180
TI  - Production of a highly charged uranium ion beam with RIKEN superconducting
      electron cyclotron resonance ion source.
AB  - A highly charged uranium (U) ion beam is produced from the RIKEN superconducting
      electron cyclotron resonance ion source using 18 and 28 GHz microwaves. The
      sputtering method is used to produce this U ion beam. The beam intensity is
      strongly dependent on the rod position and sputtering voltage. We observe that
      the emittance of U(35+) for 28 GHz microwaves is almost the same as that for 18
      GHz microwaves. It seems that the beam intensity of U ions produced using 28 GHz
      microwaves is higher than that produced using 18 GHz microwaves at the same Radio
      Frequency (RF) power.

PMID- 22380181
TI  - The preliminary tests of the superconducting electron cyclotron resonance ion
      source DECRIS-SC2.
AB  - A new compact version of the "liquid He-free" superconducting ECR ion source, to
      be used as an injector of highly charged heavy ions for the MC-400 cyclotron, is
      designed and built at the Flerov Laboratory of Nuclear Reactions in collaboration
      with the Laboratory of High Energy Physics of JINR. The axial magnetic field of
      the source is created by the superconducting magnet and the NdFeB hexapole is
      used for the radial plasma confinement. The microwave frequency of 14 GHz is used
      for ECR plasma heating. During the first tests, the source shows a good enough
      performance for the production of medium charge state ions. In this paper, we
      will present the design parameters and the preliminary results with gaseous ions.

PMID- 22380182
TI  - Transport and emittance study for 18 GHz superconducting-ECR ion source at RCNP.
AB  - As the upgrade program of the azimuthally varying field (AVF) cyclotron is at the
      cyclotron facility of the RCNP, Osaka University for the improvement of the
      quality, stability, and intensity of accelerated beams, an 18 GHz superconducting
      (SC) ECR ion source has been installed to increase beam currents and to extend
      the variety of ions, especially for highly charged heavy ions which can be
      accelerated by RCNP AVF cyclotron. The production development of several ions
      such as B, O, N, Ne, Ar, Ni, Kr, and Xe has been performed by Yorita et al. [Rev.
      Sci. Instrum. 79, 02A311(2008); 81, 02A332 (2010)]. Further studies for the beam
      transport have been done in order to improve the beam current more for injection
      of cyclotron. The effect of field leakage of AVF main coil is not negligible and
      additional steering magnet has been installed and then beam transmission has been
      improved. The emittance monitor has also been developed for the purpose of
      investigating correlation between emittance of beam from ECR ion sources and
      injection efficiency. The monitor consists with BPM82 with rotating wire for fast
      measurement for efficient study.

PMID- 22380183
TI  - Towards a better comprehension of plasma formation and heating in high
      performances electron cyclotron resonance ion sources (invited).
AB  - Further improvements of electron cyclotron resonance ion sources (ECRIS) output
      currents and average charge state require a deep understanding of electron and
      ion dynamics in the plasma. This paper will discuss the most recent advances
      about modeling of non-classical evidences like the sensitivity of electron energy
      distribution function to the magnetic field detuning, the influence of plasma
      turbulences on electron heating and ion confinement, the coupling between
      electron and ion dynamics. All these issues have in common the non-homogeneous
      distribution of the plasma inside the source: the abrupt density drop at the
      resonance layer regulates the heating regimes (from collective to turbulent), the
      beam formation mechanism and emittance. Possible means to boost the performances
      of future ECRIS will be proposed. In particular, the use of Bernstein waves, in
      preliminary experiments performed at Laboratori Nazionali del Sud (LNS) on MDIS
      (microwave discharge ion sources)-type sources, has permitted to sustain largely
      overdense plasmas enhancing the warm electron temperature, which will make
      possible in principle the construction of sources for high intensity multicharged
      ions beams with simplified magnetic structures.

PMID- 22380184
TI  - A collimator for hot plasma x-ray diagnostics in ion sources.
AB  - We present a collimator configuration for measuring energy resolved x-ray plasma
      volume bremsstrahlung emitted, e.g., by an ECRIS. Special attention we paid to
      shielding the detector against interfering Compton scattered radiation and wall
      bremsstrahlung stemming from the collimator entrance aperture. We estimate the
      efficiency for shielding of Compton scattered radiation at least attainable by
      this arrangement.

PMID- 22380185
TI  - Multigan(r): first experimental results.
AB  - A new design of a multicharged ion source based on the MONO1000 ECRIS has been
      presented at the last ECR ion source (ECRIS) Workshop 2010. [L. Maunoury et al.,
      in Proceedings of the XIXth International Workshop on ECR Ion Sources, Grenoble,
      France, 23-26 August 2010] This source has not only two opening at both ends but
      also a large space in the middle of the source enabling a direct contact with the
      ECR plasma. The source has been assembled mechanically and put on a test bench at
      the Pantechnik company. The primary tests have shown that the plasma ignition
      occurred at low pressure (10(-6) mbar) and low RF power (10 W). The first
      experimental results (<Q> = 1.30 for Ar and 1.85 for Xe) demonstrated the
      potential of this ion source in production of multicharged ion beams.

PMID- 22380186
TI  - Roadmap for the design of a superconducting electron cyclotron resonance ion
      source for Spiral2.
AB  - A review of today achieved A/Q = 3 heavy ions beams is proposed. The daily
      operation A/Q = 3 ion beam intensities expected at Spiral2 are at the limit or
      above best record 3rd generation electron cyclotron resonance ion source (ECRIS)
      intensities. The necessity to build a new fully superconducting to fulfill these
      requirements is outlined. A discussion on the volume of the future source is
      proposed and the minimum value of 12 liters is derived. An analysis of the x-ray
      absorption superconducting ECRIS is presented based on VENUS experimental data
      and geometry. This study underlines the necessity to include a complete x-ray
      study at the time of source conception. The specifications foreseen for the new
      ECRIS are presented, followed with the roadmap for the design.

PMID- 22380187
TI  - Microgan electron cyclotron resonance ion source in a Van de Graaff accelerator
      terminal.
AB  - The Van de Graaff accelerator at IRMM works since many years providing proton,
      deuteron, and helium beams for nuclear data measurements. The original ion source
      was of RF type with quartz bottle. This kind of source, as well known, needs
      regular maintenance for which the accelerator tank must be completely opened. The
      heavy usage at high currents of the IRMM accelerator necessitated an opening
      about once every month. In 2010, the full permanent magnet Microgan electron
      cyclotron resonance (ECR) ion source from PANTECHNIK was installed into a new
      terminal platform together with a solid state amplifier of 50 W, a dedicated
      dosing system for 4 gases (with respective gas bottles H(2), D(2), He, and Ar),
      and a set of dedicated power supplies and electronic devices for the remote
      tuning of the source. The new system shows a very stable behaviour of the
      produced beam allowing running the Van de Graaf without maintenance for several
      months. This contribution will describe the full installed system in details
      (working at high pressure in the terminal, spark effects, and optic of the
      extraction), as well as beam results in dc or pulsed mode.

PMID- 22380188
TI  - Status and special features of the Atomki ECR ion source.
AB  - The ECR ion source has been operating in ATOMKI (Debrecen) since 1996. During the
      past 15 years lots of minor and numerous major technical modifications have been
      carried out on the ECRIS. Many of these changes aimed the increasing of beams
      charge, intensity, and the widening of the ion choice. Another group of the
      modifications were performed to develop special, non-standard operation modes or
      to produce peculiar plasmas and beams.

PMID- 22380189
TI  - Optimization of gas utilization efficiency for short-pulsed electron cyclotron
      resonance ion source.
AB  - Numerical analysis of (6)He atoms utilizing efficiency in the ion source with
      powerful gyrotron heating is performed in present work using zero-dimensional
      balanced model of ECR discharge in a magnetic trap. Two ways of creation of ion
      source with high gas utilization efficiency (up to 60%-90%) are suggested.

PMID- 22380190
TI  - Modification of anisotropic plasma diffusion via auxiliary electrons emitted by a
      carbon nanotubes-based electron gun in an electron cyclotron resonance ion
      source.
AB  - The diffusion mechanism in magnetized plasmas is a largely debated issue. A short
      circuit model was proposed by Simon, assuming fluxes of lost particles along the
      axial (electrons) and radial (ions) directions which can be compensated, to
      preserve the quasi-neutrality, by currents flowing throughout the conducting
      plasma chamber walls. We hereby propose a new method to modify Simon's currents
      via electrons injected by a carbon nanotubes-based electron gun. We found this
      improves the source performances, increasing the output current for several
      charge states. The method is especially sensitive to the pumping frequency.
      Output currents for given charge states, at different auxiliary electron
      currents, will be reported in the paper and the influence of the frequency tuning
      on the compensation mechanism will be discussed.

PMID- 22380191
TI  - Pantechnik new superconducting ion source: PantechniK Indian Superconducting Ion
      Source.
AB  - The new ECR ion source PantechniK Indian Superconducting Ion Source (PKISIS) was
      recently commissioned at Pantechnik. Three superconducting coils generate the
      axial magnetic field configuration, while the radial magnetic field is done with
      the multi-layer permanent magnets. Special care was devoted to the design of the
      hexapolar structure, allowing a maximum magnetic field of 1.32 T at the wall of
      the 82 mm diameter plasma chamber. The three superconducting coils using low
      temperature superconducting wires are cooled by a single double stage cryo-cooler
      (4.2 K). Cryogen-free technology is used, providing reliability and easy
      maintenance at low cost. The maximum installed RF power (18.0 GHz) is of 2 kW.
      Metallic beams can be produced with an oven (T(max) = 1400  degrees C) installed
      with an angle of 5 degrees  with respect to the source axis or a sputtering
      system, mounted on the axis of the source. The beam extraction system is
      constituted of three electrodes in accel-decel configuration. The new source of
      Pantechnik is conceived for reaching optimum performances at 18 GHz RF
      frequencies. PKISIS magnetic fields are 2.1 T axial B(inj) and 1.32 T radial
      field in the wall, variable B(min) with an independent coil and a large and
      opened extraction region. Moreover, PKISIS integrates modern design concepts,
      like RF direct injection (2 kW availability), dc-bias moving disk, out-of-axis
      oven and axial sputtering facility for metal beams. Finally, PKISIS is also
      conceived in order to operate in a high-voltage platform with minor power
      consumption.

PMID- 22380192
TI  - Preliminary results of the International Fusion Materials Irradiation Facility
      deuteron injector.
AB  - In the framework of the IFMIF-EVEDA project (International Fusion Materials
      Irradiation Facility-Engineering Validation and Engineering Design Activities),
      CEA/IRFU is in charge of the design, construction, and characterization of the
      140 mA continuous deuteron injector, including the source and the low energy beam
      line. The electron cyclotron resonance ion source which operates at 2.45 GHz is
      associated with a 4-electrode extraction system in order to minimize beam
      divergence at the source exit. Krypton gas injection is foreseen in the 2
      solenoid low energy beam line. Such Kr injection will allow reaching a high level
      of space charge compensation in order to improve the beam matching at the radio
      frequency quadrupole (RFQ) entrance. The injector construction is now completed
      on the Saclay site and the first plasma and beam production has been produced in
      May 2011. This installation will be tested with proton and deuteron beams either
      in pulsed or continuous mode at Saclay before shipping to Japan. In this paper,
      after a brief description of the installation, the preliminary results obtained
      with hydrogen gas injection into the plasma chamber will be reported.

PMID- 22380193
TI  - Low energy Fe+ beam irradiation to C60 thin film.
AB  - We have developed an electron cyclotron resonance ion source apparatus, which is
      designed for the production of endohedral fullerene. In this study, we irradiated
      the Fe(+) beam to the C(60) thin film. We changed the experimental condition of
      the dose and the ion energy. We could observe the Fe + C(60) peak by analysis of
      the time-of-flight mass spectrometry. The highest intensity of the Fe + C(60)
      peak was observed at the ion energy of 200 eV. The Fe + C(60) peak intensity
      tended to become high in the case of long irradiation time and large dose.

PMID- 22380194
TI  - Manufacturing of a superconducting magnet system for 28 GHz electron cyclotron
      resonance ion source at KBSI.
AB  - A magnet system for a 28 GHz electron cyclotron resonance ion source is being
      developed by the Korea Basic Science Institute. The configuration of the magnet
      system consists of 3 solenoid coils for a mirror magnetic field and 6 racetrack
      coils for a hexapole magnetic field. They can generate axial magnetic fields of
      3.6 T at the beam injection part and 2.2 T at the extraction part. A radial
      magnetic field of 2.1 T is achievable at the plasma chamber wall. A step type
      winding process was employed in fabricating the hexapole coil. The winding
      technique was confirmed through repeated cooling tests. Superconducting magnets
      and a cryostat system are currently being manufactured.

PMID- 22380195
TI  - The impact of plasma-wall interaction on the gas mixing efficiency in electron
      cyclotron resonance ion source.
AB  - It is generally accepted that different effects are necessary to explain the gas
      mixing method of increasing the output of highly charged ions from an ECRIS. The
      two most important effects are the mass effect and the dilution effect. Their
      relative weights have not been determined experimentally yet, but it is generally
      assumed that the mass effect is dominant in standard ECRIS installations with
      stainless steel plasma chambers. In order to gain more insight into the physics
      of the gas mixing effect and in particular on the relevance of the dilution
      process, we have carried out a study where we have investigated the role of the
      plasma-wall interaction on the gas mixing effect. In this contribution, we shall
      discuss Charge state distributions spectra, measured at the Frankfurt ECRIS using
      different working gases, pure argon, a mixture of argon and oxygen, and argon
      mixed with neon.

PMID- 22380196
TI  - Plasma studies on electron cyclotron resonance light ion source at CEA/Saclay.
AB  - By the 90s, the CEA has undertaken to develop the production of intense light ion
      beams from unconfined ECR plasma. Today, three sources for IPHI, SPIRAL2, and
      IFMIF projects (respectively, 100 mA of H(+), 8 mA of D(+), and 140 mA of D(+))
      are installed at CEA/Saclay. In order to improve performances and decrease
      dimensions of these sources, it is necessary to better understand the mechanisms
      involved in the production and extraction of particles. As a consequence,
      theoretical and experimental studies are being carried out. We present a
      theoretical study based on SOLMAXP, a home-made particle-in-cell code. The aim is
      to investigate the possibility of reducing the plasma chamber size without loss
      of beam characteristics. This code has been validated by beam intensity
      measurements on a permanent magnet based source, producing a proton beam of 30 mA
      at 40 kV on the test bench BETSI. In order to reduce experimentally the
      dimensions of plasma chamber, a new source, named ALISES with variable plasma
      chamber volume, is under assembly.

PMID- 22380197
TI  - Upgraded vacuum arc ion source for metal ion implantation.
AB  - Vacuum arc ion sources have been made and used by a large number of research
      groups around the world over the past twenty years. The first generation of
      vacuum arc ion sources (dubbed "Mevva," for metal vapor vacuum arc) was developed
      at Lawrence Berkeley National Laboratory in the 1980s. This paper considers the
      design, performance parameters, and some applications of a new modified version
      of this kind of source which we have called Mevva-V.Ru. The source produces broad
      beams of metal ions at an extraction voltage of up to 60 kV and a time-averaged
      ion beam current in the milliampere range. Here, we describe the Mevva-V.Ru
      vacuum arc ion source that we have developed at Tomsk and summarize its beam
      characteristics along with some of the applications to which we have put it. We
      also describe the source performance using compound cathodes.

PMID- 22380198
TI  - Design of the injection beamline for the Californium Rare Isotope Breeder Upgrade
      electron beam ion source charge breeder.
AB  - The design of the ion injection line connecting the electron beam ion source
      (EBIS) charge breeder and the Californium Rare Isotope Breeder Upgrade radio
      frequency quadrupole cooler-buncher at the Argonne Tandem Linear Accelerator
      System was investigated with particle tracking simulations. The injection line
      was configured to accommodate several differential pumping sections, individual
      optical components were optimized to minimize emittance growth, and the ion beam
      parameters were matched with the EBIS electron beam acceptance to minimize losses
      upon injection.

PMID- 22380199
TI  - Angular distribution of plasma in the vacuum arc ion source.
AB  - This paper presents measurements of the angular distribution of the plasma
      components and different charge states of metal ions generated by a MEVVA-type
      ion source and measured by a time-of-flight mass-spectrometer. The experiments
      were performed for different cathode materials (Al, Cu, and Ti) and for different
      parameters of the vacuum arc discharge. The results are compared with prior
      results reported by other authors. The influence of different discharge
      parameters on the angular distribution in a vacuum arc source is discussed.

PMID- 22380200
TI  - Ion optics of RHIC electron beam ion source.
AB  - RHIC electron beam ion source has been commissioned to operate as a versatile ion
      source on RHIC injection facility supplying ion species from He to Au for
      Booster. Except for light gaseous elements RHIC EBIS employs ion injection from
      several external primary ion sources. With electrostatic optics fast switching
      from one ion species to another can be done on a pulse to pulse mode. The design
      of an ion optical structure and the results of simulations for different ion
      species are presented. In the choice of optical elements special attention was
      paid to spherical aberrations for high-current space charge dominated ion beams.
      The combination of a gridded lens and a magnet lens in LEBT provides flexibility
      of optical control for a wide range of ion species to satisfy acceptance
      parameters of RFQ. The results of ion transmission measurements are presented.

PMID- 22380201
TI  - Development of high current Bi and Au beams for the synchrotron operation at the
      GSI accelerator facility.
AB  - In this work, the latest results of developing high current ion beams of Au and
      Bi at GSI facility are described. The difficulties in the production of required
      charge state in vacuum arc discharge ion sources using the pure materials in the
      cathodes are discussed. As a possible solution, admix of a small amount of more
      refractory metal to the cathode material is considered. As a significant result,
      a dramatic improvement in the production of high charge state Bi ions using the
      mixed Bi-Cu cathodes (with 8%-15% of Cu admixed) compared to pure Bi cathodes is
      presented. The preliminary results of investigation of the material structure of
      Bi-Cu cathodes are discussed. As a next step, it is planned to test the
      composition of Au with Pd, Zr, and Fe as cathode materials.

PMID- 22380202
TI  - The design of an electron gun switchable between immersed and Brillouin flow.
AB  - An electron gun, which can be switched from immersed flow to Brillouin flow
      during operation, may have advantages for charge breeders as well as for electron
      beam ion sources and traps (EBISTs). For EBISTs this allows to change the current
      density according to the repetition frequency and charge state, for charge
      breeders and EBISTs a lower current density in immersed flow provides higher
      acceptance for injected ions, while the higher current density in Brillouin flow
      results in shorter breeding times and a lower emittance for the extracted beam.
      Therefore, we have designed such a gun for an EBIS with 5 T central magnetic
      field and without the use of iron and moving the gun. The gun was placed in the
      axial fringing field of the 5 T solenoid in such a position that a gate valve can
      be placed between the gun and the cryostat to allow for simple maintenance. The
      field at the cathode surface turned out to be only 0.05 T, which is not enough to
      focus 50 A/cm(2) at a few kV. However, if a small normal conducting solenoid is
      placed over the vacuum tube in position of the gun, a field of 0.1 T may be
      obtained. With this the use of LaB(6) as cathode material results in a magnetic
      compression of 44 and therewith in a focused current density in the trap region
      of more than 2000 A/cm(2). By reversing the current in the gun solenoid the
      cathode field can easily compensated to zero. By proper design of the electrodes
      and the compression region, the gun will be able to deliver a beam in Brillouin
      flow. While this is interesting by itself--remember the "super-compression"
      reported on CRYEBIS-I--any magnetic field between zero and the value for immersed
      flow will result in an electron beam with a wide range of adjustable high current
      densities. The design tools used have been INTMAG(C) for the calculation of
      magnetic fields, EGN2(C) for the simulation of the gun and ANALYSE(C) for
      detailed analysis of the results (for more information see www.egun-igun.com).

PMID- 22380203
TI  - Production of low-Z ions in the Dresden superconducting electron ion beam source
      for medical particle therapy.
AB  - We report on experiments with a new superconducting electron beam ion source
      (EBIS-SC), the Dresden EBIS-SC, with the objective to meet the main requirements
      for their application in particle-therapy facilities. Synchrotrons as well as
      innovative accelerator concepts, such as high-gradient linacs which are driven by
      a large-current cyclotron (CYCLINACS) and direct drive RF linear accelerators may
      benefit from the advantages of EBISs in regard to their functional principle.
      First experimental studies of the production of low-Z ions such as H(+), H(2)(+),
      H(3)(+), C(4+), and C(6+) are presented. Particular attention is paid to the ion
      output, i.e., the number of ions per pulse and per second, respectively.
      Important beam parameters in this context are, among others, ion pulse shaping,
      pulse repetition rates, beam emittance, and ion energy spread.

PMID- 22380204
TI  - A particle-in-cell Monte Carlo code for electron beam ion source simulation.
AB  - FAR-TECH, Inc., has developed a particle-in-cell Monte Carlo code (EBIS-PIC) to
      model ion motions in an electron beam ion source (EBIS). First, a steady state
      electron beam is simulated by the PBGUNS code (see http://far
      tech.com/pbguns/index.html). Then, the injected primary ions and the ions from
      the background neutral gas are tracked in the trapping region using Monte Carlo
      method. Atomic collisions and Coulomb collisions are included in the EBIS-PIC
      model. The space charge potential is updated by solving the Poisson equation each
      time step. The preliminary simulation results are presented and compared with BNL
      electron beam test stand (EBTS) fast trapping experiments.

PMID- 22380205
TI  - Influence of discharge gap on the discharge stability in a short vacuum arc ion
      source.
AB  - The influence of the discharge gap between cathode and anode on the discharge
      stability in a short vacuum arc (SVA) ion source is presented in this paper.
      Planar cathode and cylindrical hollow anode made of titanium are investigated.
      There is a great need in present accelerator injection research for SVA source to
      produce the small deviation of the ion current beam. Current research shows that
      increasing the short discharge gap can reduce the level of ion current deviation
      and ion charge deviation from 29% and 31% to 15% and 17%, respectively. A
      microplasma plume generation mechanism in SVA and scanning electron microscopic
      results can be used to explain this interesting phenomenon.

PMID- 22380206
TI  - Shunting arc plasma source for pure carbon ion beam.
AB  - A plasma source is developed using a coaxial shunting arc plasma gun to extract a
      pure carbon ion beam. The pure carbon ion beam is a new type of deposition system
      for diamond and other carbon materials. Our plasma device generates pure carbon
      plasma from solid-state carbon material without using a hydrocarbon gas such as
      methane gas, and the plasma does not contain any hydrogen. The ion saturation
      current of the discharge measured by a double probe is about 0.2 mA/mm(2) at the
      peak of the pulse.

PMID- 22380207
TI  - Liquid metal alloy ion source based metal ion injection into a room-temperature
      electron beam ion source.
AB  - We have carried out a series of measurements demonstrating the feasibility of
      using the Dresden electron beam ion source (EBIS)-A, a table-top sized, permanent
      magnet technology based electron beam ion source, as a charge breeder. Low
      charged gold ions from an AuGe liquid metal alloy ion source were injected into
      the EBIS and re-extracted as highly charged ions, thereby producing charge states
      as high as Au(60 +). The setup, the charge breeding technique, breeding
      efficiencies as well as acceptance and emittance studies are presented.

PMID- 22380208
TI  - Physics research and technology developments of electron string ion sources.
AB  - The most recent experimental information on electron string phenomenon, such as
      two step transition to electron string state, stability of e-strings in condition
      of electron energy recuperation, are described. The new technology developments
      of electron string ion sources (ESIS) include pulse injection of gaseous species
      in e-string and its efficient conversion to ion beams, slow ion extraction, ion
      ion cooling of heavy ions with CH(4) coolant, and a progress in the construction
      of the new Joint Institute for Nuclear Research ESIS with 6 T solenoid are
      briefly considered.

PMID- 22380209
TI  - Characteristic of a triple-cathode vacuum arc plasma source.
AB  - In order to generate a better ion beam, a triple-cathode vacuum arc plasma source
      has been developed. Three plasma generators in the vacuum arc plasma source are
      equally located on a circle. Each generator initiated by means of a high-voltage
      breakdown between the cathode and the anode could be operated separately or
      simultaneously. The arc plasma expands from the cathode spot region in vacuum. In
      order to study the behaviors of expanding plasma plume generated in the vacuum
      arc plasma source, a Langmuir probe array is employed to measure the saturated
      ion current of the vacuum arc plasma source. The time-dependence profiles of the
      saturated current density of the triple vacuum arc plasma source operated
      separately and simultaneously are given. Furthermore, the plasma characteristic
      of this vacuum arc plasma source is also presented in the paper.

PMID- 22380210
TI  - Optimizing the front end test stand high performance H- ion source at RAL.
AB  - The aim of the front end test stand project is to demonstrate that chopped low
      energy H(-) beams of high quality can be produced. The beam line currently
      consists of the ion source, a 3 solenoid low energy beam transport and a suite of
      diagnostics. A brief status report of the radio frequency quadrupole is given.
      This paper details the work to optimize the ion source performance. A new high
      power pulsed discharge power supply with greater reliability has been developed
      to allow long term, stable operation at 50 Hz with a 60 A, 2.2 ms discharge pulse
      and up to 100 A at 1.2 ms. The existing extraction power supply has been modified
      to operate up to 22 kV. Results from optical spectroscopy measurements and their
      application to source optimization are summarized. Source emittances and beam
      currents of 60 mA are reported.

PMID- 22380211
TI  - Matrix of small-radius radio-frequency discharges as a volume-production based
      source of negative hydrogen ions.
AB  - Based on experience from a work--both theoretical and experimental one--on
      negative hydrogen ion beam sources studied regarding fusion applications, a novel
      design of a rf source with volume production of the ions is proposed. The
      suggestion is for a source constructed as a matrix of small-radius tandem
      discharges (with magnetic filters largely extended over the discharge length),
      inductively driven (by a single coil, for the whole matrix) and with a single
      aperture extraction from each of them.

PMID- 22380212
TI  - Status of the plasma generator of the superconducting proton linac.
AB  - In the framework of the superconducting proton linac (SPL) study at CERN, a new
      non-cesiated H(-) plasma generator driven by an external 2 MHz RF antenna has
      been developed and successfully operated at repetition rates of 50 Hz, pulse
      lengths of up to 3 ms, and average RF powers of up to 3 kW. The coupling
      efficiency of RF power into the plasma was determined by the cooling water
      temperatures and the analysis of the RF forward and reflected power and the
      antenna current and amounts to 50%-60%. The plasma resistance increases between
      10 kW and 40 kW RF power from about 0.45 Omega to 0.65 Omega. Measurements of RF
      power dissipated in the ferrites and the magnets on a test bench show a 5-fold
      decrease of the power losses for the magnets when they are contained in a Cu box,
      thus validating the strategy of shielding the magnets with a high electrical
      conductivity material. An air cooling system was installed in the SPL plasma
      generator to control the temperatures of the ferrites despite hysteresis losses
      of several Watts.

PMID- 22380213
TI  - Initial study of the optical spectrum of the ISIS H- ion source plasma.
AB  - The front end test stand is being constructed at the Rutherford Appleton
      Laboratory, with the aim of producing a 60 mA, 2 ms, 50 Hz, perfectly chopped H(
      ) ion beam. To meet the beam requirements, a more detailed understanding of the
      ion source plasma is required. To this end, an initial study is made of the
      optical spectrum of the plasma using a digital spectrometer. The atomic and
      molecular emission lines of hydrogen and caesium are clearly distinguished and a
      quantitative comparison is made when the ion source is run in different
      conditions. The electron temperature is 0.6 eV and measured line widths vary by
      up to 75%.

PMID- 22380214
TI  - Simulation of H- ion source extraction systems for the Spallation Neutron Source
      with Ion Beam Simulator.
AB  - A three-dimensional ion optical code IBSimu, which is being developed at the
      University of Jyvaskyla, features positive and negative ion plasma extraction
      models and self-consistent space charge calculation. The code has been utilized
      for modeling the existing extraction system of the H(-) ion source of the
      Spallation Neutron Source. Simulation results are in good agreement with
      experimental data. A high-current extraction system with downstream electron
      dumping at intermediate energy has been designed. According to the simulations it
      provides lower emittance compared to the baseline system at H(-) currents
      exceeding 40 mA. A magnetic low energy beam transport section consisting of two
      solenoids has been designed to transport the beam from the alternative
      electrostatic extraction systems to the radio frequency quadrupole.

PMID- 22380215
TI  - Optimization of negative ion current in a compact microwave driven upper hybrid
      resonance multicusp plasma source.
AB  - Performance of a microwave driven upper hybrid resonance multicusp plasma source
      as a volume negative ion source is reported. Microwaves are directly launched
      into the plasma chamber predominantly in the TE(11) mode. The source is operated
      at different discharge conditions to obtain the optimized negative H(-) ion
      current which is ~33 MUA (0.26 mA/cm(2)). Particle balance equations are solved
      to estimate the negative ion density, which is compared with the experimental
      results. Future prospects of the source are discussed.

PMID- 22380216
TI  - Development of a versatile multiaperture negative ion source.
AB  - A 60 kV ion source (9 beamlets of 15 mA each of H(-)) and plasma generators are
      being developed at Consorzio RFX and INFN-LNL, for their versatility in
      experimental campaigns and for training. Unlike most experimental sources, the
      design aimed at continuous operation. Magnetic configuration can achieve a
      minimum ?B? trap, smoothly merged with the extraction filter. Modular design
      allows for quick substitution and upgrading of parts such as the extraction and
      postacceleration grids or the electrodes in contact with plasma. Experiments with
      a radio frequency plasma generator and Faraday cage inside the plasma are also
      described.

PMID- 22380217
TI  - Forty years of surface plasma source development.
AB  - The cesiation effect, a significant enhancement of negative ion emission from a
      gas discharge with decrease of co-extracted electron current below negative ion
      current, was observed for the first time on July 1, 1971 by placing into the
      discharge a compound with 1 mg of cesium. Subsequent developments of surface
      plasma sources (SPS) for highly efficient negative ion production caused by the
      interaction of plasma particles with electrodes on which the adsorbed cesium
      reduced the surface work function are described. In the last 40 years, the
      intensity of negative ion beams has increased by cesiation up to 10(4) times from
      3 mA to tens of amperes. Here, the main attention is concentrated on earlier SPS
      developments because recent results are well known and widely available.

PMID- 22380218
TI  - Correlation between the plasma parameters and the extracted current density in
      the volume-production based sources of negative hydrogen ions.
AB  - Unified description of a volume-production based source of negative hydrogen
      ions, including its three regions--the driver, the plasma expansion through the
      magnetic filter, and the extraction of the ions at the position of the first
      electrode of the extraction system--is presented within a two-dimensional fluid
      plasma model. The results display the crucial role of the potential of the first
      electrode of the extraction system and show that the optimized conditions for the
      source operation should ensure proper balance between the local and non-local
      processes in the discharge. The role of the material of the plasma electrode is
      also discussed.

PMID- 22380219
TI  - MeV negative ion source from ultra-intense laser-matter interaction.
AB  - Experimental demonstration of negative ion acceleration to MeV energies from sub
      micron size droplets of water spray irradiated by ultra-intense laser pulses is
      presented. Thanks to the specific target configuration and laser parameters, more
      than 10(9) negative ions per steradian solid angle in 5% energy bandwidth are
      accelerated in a stable and reliable manner. To our knowledge, by virtue of the
      ultra-short duration of the emission, this is by far the brightest negative ion
      source reported. The data also indicate the existence of beams of neutrals with
      at least similar numbers and energies.

PMID- 22380220
TI  - Beam purification by photodetachment (invited).
AB  - Ion beam purity is of crucial importance to many basic and applied studies in
      nuclear science. Selective photodetachment has been proposed to suppress unwanted
      species in negative ion beams while preserving the intensity of the species of
      interest. A highly efficient technique based on photodetachment in a gas-filled
      radio frequency quadrupole ion cooler has been demonstrated. In off-line
      experiments with stable ions, up to 10(4) times suppression of the isobar
      contaminants in a number of interesting radioactive negative ion beams has been
      demonstrated. For selected species, this technique promises new experimental
      possibilities in studies on exotic nuclei, accelerator mass spectrometry, and
      fundamental properties of negative atomic and molecular ions.

PMID- 22380221
TI  - Surface plasma source with saddle antenna radio frequency plasma generator.
AB  - A prototype RF H(-) surface plasma source (SPS) with saddle (SA) RF antenna is
      developed which will provide better power efficiency for high pulsed and average
      current, higher brightness with longer lifetime and higher reliability. Several
      versions of new plasma generators with small AlN discharge chambers and different
      antennas and magnetic field configurations were tested in the plasma source test
      stand. A prototype SA SPS was installed in the Spallation Neutron Source (SNS)
      ion source test stand with a larger, normal-sized SNS AlN chamber that achieved
      unanalyzed peak currents of up to 67 mA with an apparent efficiency up to 1.6
      mA/kW. Control experiments with H(-) beam produced by SNS SPS with internal and
      external antennas were conducted. A new version of the RF triggering plasma gun
      has been designed. A saddle antenna SPS with water cooling is fabricated for high
      duty factor testing.

PMID- 22380222
TI  - Surface plasma source with anode layer plasma accelerator.
AB  - Proposed plasma generation system can be used for high current negative ion beam
      production and for directed deposition by flux of sputtered neutrals and negative
      ions. The main mechanism of negative ion formation in surface plasma sources is
      the secondary emission from low work function surface bombarded by a flux of
      positive ion or neutrals. The emission of negative ions is enhanced significantly
      by introducing a small amount of cesium or other substance with low ionization
      potential. In the proposed source are used positive ions generated by Hall drift
      plasma accelerator (anode layer plasma accelerator or plasma accelerator with
      insulated channel, with cylindrical or race track configuration of emission
      slit). The target-emitter is bombarded by the ion beam accelerated in crossed ExB
      fields. Negative ions are extracted from the target surface with geometrical
      focusing and are accelerated by negative voltage applied between emitter and
      plasma, contacting with the plasma accelerator. Hall drift ion source has a
      special design with a space for passing of the emitted negative ions and
      sputtered particles through the positive ion source.

PMID- 22380223
TI  - Absolute beam brightness detector.
AB  - In generally accepted emittance measurement, main attention is concentrated on
      emittance areas E(x), E(y) occupied by desired part of ion beam in transverse
      phase space and shape of these areas. The absolute beam phase density
      (brightness) as usually is not measured directly and the average beam brightness
      B is calculated from a beam intensity I and the transverse emittances. In the ion
      source and low energy beam transport (LEBT) optimization, it is important to
      preserve the beam brightness because some aberration of ion optic and beam
      instabilities can decrease the brightness of the central part of ion beam
      significantly. For these brightness measurements, it is convenient to use an
      absolute beam brightness detector with the brightness determination from one
      short considered in this article.

PMID- 22380224
TI  - Plasma characterization of the superconducting proton linear accelerator plasma
      generator using a 2 MHz compensated Langmuir probe.
AB  - The CERN study for a superconducting proton Linac (SPL) investigates the design
      of a pulsed 5 GeV Linac operating at 50 Hz. As a first step towards a future SPL
      H(-) volume ion source, a plasma generator capable of operating at Linac4 or
      nominal SPL settings has been developed and operated at a dedicated test stand.
      The hydrogen plasma is heated by an inductively coupled RF discharge e(-) and
      ions are confined by a magnetic multipole cusp field similar to the currently
      commissioned Linac4 H(-) ion source. Time-resolved measurements of the plasma
      potential, temperature, and electron energy distribution function obtained by
      means of a RF compensated Langmuir probe along the axis of the plasma generator
      are presented. The influence of the main tuning parameters, such as RF power and
      frequency and the timing scheme is discussed with the aim to correlate them to
      optimum H(-) ion beam parameters measured on an ion source test stand. The
      effects of hydrogen injection settings which allow operation at 50 Hz repetition
      rate are discussed.

PMID- 22380225
TI  - Extraction of negative hydrogen ions from a compact 14 GHz microwave ion source.
AB  - A pair of permanent magnets has formed enough intensity to realize electron
      cyclotron resonance condition for a 14 GHz microwave in a 2 cm diameter 9 cm long
      alumina discharge chamber. A three-electrode extraction system assembled in a
      magnetic shielding has formed a stable beam of negative hydrogen ions (H(-)) in a
      direction perpendicular to the magnetic field. The measured H(-) current density
      was about 1 mA/cm(2) with only 50 W of discharge power, but the beam intensity
      had shown saturation against further increase in microwave power. The beam
      current decreased monotonically against increasing pressure.

PMID- 22380226
TI  - Analysis of H atoms in a negative ion source plasma with the non-equilibrium
      electron energy distribution function.
AB  - In negative ion sources for the neutral beam injection, it is important to
      calculate H atom flux onto the plasma grid (PG) surface for the evaluation of H(
      ) production on the PG surface. We have developed a neutral (H(2) molecules and H
      atoms) transport code. In the present study, the neutral transport code is
      applied to the analysis of the H(2) and H transport in a NIFS-R&D ion source in
      order to calculate the flux onto the PG surface. Taking into account non
      equilibrium feature of the electron energy distribution function (EEDF), i.e.,
      the fast electron component, we have done the neutral transport simulation. The
      results suggest that the precise evaluation of the EEDF, especially in the energy
      range 15 eV < E < 30 eV is important for the dissociation rate of H(2) molecules
      by the electron impact collision and the resultant H atom flux on the PG.

PMID- 22380227
TI  - Research and development of H- ion source and low energy beam transport for a
      kaon-neutrino factory.
AB  - A baseline H(-) ion source and low energy beam transport (LEBT) system have been
      identified for Project X. The filament-discharge H(-) ion source has been
      fabricated by D-Pace, Inc. and is now in operation at LBNL. The source is capable
      of delivering over 10 mA of H(-) beam in cw operation with normalized 4 rms
      emittances less than 0.7 pi mm mrad. A two-solenoid magnetic lens LEBT system has
      been design. The design has been validated with simulations of beam transport for
      5 mA 30 keV H(-) beams using various simulation codes.

PMID- 22380228
TI  - Effect of non-uniform electron energy distribution function on plasma production
      in large arc driven negative ion source.
AB  - Spatially non-uniform electron energy distribution function (EEDF) in an arc
      driven negative ion source (JAEA 10A negative ion source: 10 A NIS) is calculated
      numerically by a three-dimensional Monte Carlo kinetic model for electrons to
      understand spatial distribution of plasma production (such as atomic and ionic
      hydrogen (H(0)/H(+)) production) in source chamber. The local EEDFs were directly
      calculated from electron orbits including electromagnetic effects and
      elastic/inelastic collision forces. From the EEDF, spatial distributions of
      H(0)/H(+) production rate were obtained. The results suggest that spatial non
      uniformity of H(0)/H(+) productions is enhanced by high energy component of EEDF.

PMID- 22380229
TI  - Radio frequency discharge with control of plasma potential distribution.
AB  - A RF discharge plasma generator with additional electrodes for independent
      control of plasma potential distribution is proposed. With positive biasing of
      this ring electrode relative end flanges and longitudinal magnetic field a
      confinement of fast electrons in the discharge will be improved for reliable
      triggering of pulsed RF discharge at low gas density and rate of ion generation
      will be enhanced. In the proposed discharge combination, the electron energy is
      enhanced by RF field and the fast electron confinement is improved by enhanced
      positive plasma potential which improves the efficiency of plasma generation
      significantly. This combination creates a synergetic effect with a significantly
      improving the plasma generation performance at low gas density. The discharge
      parameters can be optimized for enhance plasma generation with acceptable
      electrode sputtering.

PMID- 22380230
TI  - Analysis of the H- ion emissive surface in the extraction region of negative ion
      sources.
AB  - To understand the plasma characteristics in the extraction region of negative H(
      ) sources is very important for the optimization of H(-) extraction from the
      sources. The profile of plasma density and electrostatic potential in the
      extraction region with and without extraction grid voltage are analyzed with a 2D
      particle in cell modeling of the NIFS-RD H(-) sources. The simulation results
      make clear the physical process forming a double ion plasma layer (which consists
      only of positive H(+) and negative H(-) ions) recently observed in the Cs-seeded
      experiments of the NIFS-R&D source in the vicinity of the extraction hole and the
      plasma grid. The results also give a useful insight into the formation mechanism
      of the plasma meniscus and the H(-) extraction process for such double ion
      plasma.

PMID- 22380231
TI  - Effects of adsorption and roughness upon the collision processes at the convertor
      surface of a plasma sputter negative ion source.
AB  - Atomic collision processes associated with surface production of negative
      hydrogen ions (H(-)) by particle reflection at molybdenum surface immersed in
      hydrogen plasma have been investigated. To calculate sputtering yields of Cs, as
      well as energy spectra and angular distributions of reflected hydrogen atoms from
      molybdenum surface by H(+) ion and Cs(+) ion bombardments, a Monte Carlo
      simulation code ACAT (Atomic Collision in Amorphous Target) was run with the
      corresponding surface conditions. A fractal surface model has been developed and
      adopted to ACAT for evaluating the effect due to roughness of target material.
      The results obtained with ACAT have indicated that the retention of hydrogen
      atoms leads to the reduction in sputtering yields of Cs, and the surface
      roughness does largely affect the sputtering yields of Cs.

PMID- 22380232
TI  - Numerical analysis of surface produced H- ions by using two-dimensional particle
      in-cell method.
AB  - The modeling and analysis of a negative ion source is proceeding by using a 2D
      particle-in-cell simulation. The effect of the H(-) ion production on the plasma
      grid (PG) surface is investigated. It is shown that with the increase of H(-)
      ions per time step, the H(-) ion current density is enhanced, while the electron
      current density decreases with increasing the H(-) production rate on the PG
      surface. These results agree well with the experimental results observed in
      typical negative ion sources. Moreover, it is found that plasma quasi-neutrality
      is held mainly by both H(+) and H(-) ions in the bulk plasma around the PG.

PMID- 22380233
TI  - Features of semiplanotron surface plasma sources.
AB  - Features of the semiplanotron surface plasma sources (SPS) with cesiation used
      for high efficient negative ion beam production from first development to modern
      condition are considered. Design features of semiplanotrons SPS with cylindrical
      and spherical geometric focusing and the features of the negative ion production
      in the semiplanotrons are reviewed. Several versions of semiplanotrons with
      efficiency up to 0.1 A of H(-) per kW of discharge power are discussed.
      Modifications of the semiplanotrons for dc operation and for heavy negative ion
      production are reviewed.

PMID- 22380234
TI  - H- radio frequency source development at the Spallation Neutron Source.
AB  - The Spallation Neutron Source (SNS) now routinely operates nearly 1 MW of beam
      power on target with a highly persistent ~38 mA peak current in the linac and an
      availability of ~90%. H(-) beam pulses (~1 ms, 60 Hz) are produced by a Cs
      enhanced, multicusp ion source closely coupled with an electrostatic low energy
      beam transport (LEBT), which focuses the 65 kV beam into a radio frequency
      quadrupole accelerator. The source plasma is generated by RF excitation (2 MHz,
      ~60 kW) of a copper antenna that has been encased with a thickness of ~0.7 mm of
      porcelain enamel and immersed into the plasma chamber. The ion source and LEBT
      normally have a combined availability of ~99%. Recent increases in duty-factor
      and RF power have made antenna failures a leading cause of downtime. This report
      first identifies the physical mechanism of antenna failure from a statistical
      inspection of ~75 antennas which ran at the SNS, scanning electron microscopy
      studies of antenna surface, and cross sectional cuts and analysis of calorimetric
      heating measurements. Failure mitigation efforts are then described which include
      modifying the antenna geometry and our acceptance/installation criteria. Progress
      and status of the development of the SNS external antenna source, a long-term
      solution to the internal antenna problem, are then discussed. Currently, this
      source is capable of delivering comparable beam currents to the baseline source
      to the SNS and, an earlier version, has briefly demonstrated unanalyzed currents
      up to ~100 mA (1 ms, 60 Hz) on the test stand. In particular, this paper
      discusses plasma ignition (dc and RF plasma guns), antenna reliability, magnet
      overheating, and insufficient beam persistence.

PMID- 22380235
TI  - Experimental development on the 18 mA, H- multi-cusp ion source at China
      Institute of Atomic Energy.
AB  - The ion source is one of the key devices for the high-intensity cyclotron, which
      exerts influence on the beam intensity and applications of the machine. The H(-)
      multi-cusp ion source developed at China Institute of Atomic Energy has been used
      to perform experimental study on beam intensity and emittance versus the bias
      voltage, arc power, lens voltage, and pressure of the ion source. Up to now, 18
      mA H(-) ion beam with emittance of 0.93 pimm mrad (four times RMS normalized
      emittance) was obtained from this ion source through the in-depth study and
      optimization on some essential factors affecting the beam intensity and quality.
      The paper will present the experimental study on the ion source as well as the
      beam test results.

PMID- 22380236
TI  - Wave frequency dependence of H- ion production and extraction in a transformer
      coupled plasma H- ion source at SNU.
AB  - The effect of rf wave frequencies on the production of H(-) ion is investigated
      in a transformer coupled plasma H(-) ion source at Seoul National University. A
      Langmuir probe is installed to measure the plasma density and temperature, and
      these plasma parameters are correlated to the extracted H(-) beam currents at
      various frequencies. The Langmuir probe is also used to measure the density of H(
      ) ions at the ion source by generating photodetachment with an Nd:YAG laser. The
      extracted H(-) currents decrease to a minimum value until 13 MHz and then,
      increase as the driving frequency increases from 13 MHz while the relative H(-)
      population measured by photodetachment monotonically decreases as the driving rf
      frequency increases from 11 MHz to 15 MHz. A potential well formed at the
      extraction region at high frequencies of more than 13 MHz is considered
      responsible for the increased H(-) beam extraction even with a lower
      photodetachment signal. The variation in the driving rf frequency not only
      affects the density and temperature of the plasma but also modifies the plasma
      potential with the existence of a filtering magnetic field and consequently,
      influences the extracted H(-) current through the extraction as well as formation
      of H(-) ions.

PMID- 22380237
TI  - Investigation of ISIS and Brookhaven National Laboratory ion source electrodes
      after extended operation.
AB  - Linac4 accelerator of Centre Europeen de Recherches Nucleaires is under
      construction and a RF-driven H(-) ion source is being developed. The beam current
      requirement for Linac4 is very challenging: 80 mA must be provided. Cesiated
      plasma discharge ion sources such as Penning or magnetron sources are also
      potential candidates. Accelerator ion sources must achieve typical reliability
      figures of 95% and above. Investigating and understanding the underlying
      mechanisms involved with source failure or ageing is critical when selecting the
      ion source technology. Plasma discharge driven surface ion sources rely on
      molybdenum cathodes. Deformation of the cathode surfaces is visible after
      extended operation periods. A metallurgical investigation of an ISIS ion source
      is presented. The origin of the deformation is twofold: Molybdenum sputtering by
      cesium ions digs few tenths of mm cavities while a growth of molybdenum is
      observed in the immediate vicinity. The molybdenum growth under hydrogen
      atmosphere is hard and loosely bound to the bulk. It is, therefore, likely to
      peel off and be transported within the plasma volume. The observation of the
      cathode, anode, and extraction electrodes of the magnetron source operated at BNL
      for two years are presented. A beam simulation of H(-), electrons, and Cs(-) ions
      was performed with the IBSimu code package to qualitatively explain the
      observations. This paper describes the operation conditions of the ion sources
      and discusses the metallurgical analysis and beam simulation results.

PMID- 22380238
TI  - Optical emission spectroscopy of the Linac4 and superconducting proton Linac
      plasma generators.
AB  - CERN's superconducting proton Linac (SPL) study investigates a 50 Hz high-energy,
      high-power Linac for H(-) ions. The SPL plasma generator is an evolution of the
      DESY ion source plasma generator currently operated at CERN's Linac4 test stand.
      The plasma generator is a step towards a particle source for the SPL, it is
      designed to handle 100 kW peak RF-power at a 6% duty factor. While the
      acquisition of an integrated hydrogen plasma optical spectrum is straightforward,
      the measurement of a time-resolved spectrum requires dedicated amplification
      schemes. The experimental setup for visible light based on photomultipliers and
      narrow bandwidth filters and the UV spectrometer setup are described. The
      H(alpha), H(beta), and H(gamma) Balmer line intensities, the Lyman band and alpha
      transition were measured. A parametric study of the optical emission from the
      Linac4 ion source and the SPL plasma generator as a function of RF-power and gas
      pressure is presented. The potential of optical emission spectrometry coupled to
      RF-power coupling measurements for on-line monitoring of short RF heated hydrogen
      plasma pulses is discussed.

PMID- 22380239
TI  - Development of a compact filament-discharge multi-cusp H- ion source.
AB  - A 14 MeV medical cyclotron with the external ion source has been designed and is
      being constructed at China Institute of Atomic Energy. The H(-) ion will be
      accelerated by this machine and the proton beam will be extracted by carbon
      strippers in dual opposite direction. The compact multi-cusp H(-) ion source has
      been developed for the cyclotron. The 79.5 mm long ion source is 48 mm in
      diameter, which is consisting of a special shape filament, ten columns of
      permanent magnets providing a multi-cusp field, and a three-electrode extraction
      system. So far, the 3 mA/25 keV H(-) beam with an emittance of 0.3 pi mm mrad has
      been obtained from the ion source. The paper gives the design details and the
      beam test results. Further experimental study is under way and an extracted beam
      of 5 mA is expected.

PMID- 22380240
TI  - Laser measurement of H- ions in a field-effect-transistor based radio frequency
      ion source.
AB  - Hydrogen negative ion density measurements are required to clarify the
      characteristics of negative ion production and ion source performance. Both of
      laser photodetachment and cavity ring down (CRD) measurements have been
      implemented to a field-effect-transistor based radio-frequency ion source. The
      density ratio of negative hydrogen ions to electrons was successfully measured by
      laser photodetachment and effect of magnetic filter field on negative ion density
      was confirmed. The calculated CRD signal showed that CRD mirrors with >99.990%
      reflectivity are required and loss of reflectivity due to cesium contamination
      should be minimized.

PMID- 22380241
TI  - Producing persistent, high-current, high-duty-factor H- beams for routine 1 MW
      operation of Spallation Neutron Source (invited).
AB  - Since 2009, the Spallation Neutron Source (SNS) has been producing neutrons with
      ion beam powers near 1 MW, which requires the extraction of ~50 mA H(-) ions from
      the ion source with a ~5% duty factor. The 50 mA are achieved after an initial
      dose of ~3 mg of Cs and heating the Cs collar to ~170  degrees C. The 50 mA
      normally persist for the entire 4-week source service cycles. Fundamental
      processes are reviewed to elucidate the persistence of the SNS H(-) beams without
      a steady feed of Cs and why the Cs collar temperature may have to be kept near
      170  degrees C.

PMID- 22380242
TI  - Charge breeding simulations for radioactive ion beam production.
AB  - The charge breeding technique is used for radioactive ion beam (RIB) production
      in order of optimizing the re-acceleration of the radioactive element ions
      produced by a primary beam in a thick target. Charge breeding is achieved by
      means of a device capable of increasing the ion charge state from 1+ to a desired
      value n+. In order to get high intensity RIB, experiments with charge breeding of
      very high efficiency could be required. To reach this goal, the charge breeding
      simulation could help to optimize the high charge state production efficiency by
      finding more proper parameters for the radioactive 1+ ions. In this paper a
      device based on an electron beam ion source (EBIS) is considered. In order to
      study that problem, a code already developed for studying the ion selective
      containment in an EBIS with RF quadrupoles, BRICTEST, has been modified to
      simulate the ion charge state breeding rate for different 1+ ion injection
      conditions. Particularly, the charge breeding simulations for an EBIS with a
      hollow electron beam have been studied.

PMID- 22380243
TI  - Development of electron beam ion source charge breeder for rare isotopes at
      Californium Rare Isotope Breeder Upgrade.
AB  - Recently, the Californium Rare Isotope Breeder Upgrade (CARIBU) to the Argonne
      Tandem Linac Accelerator System (ATLAS) was commissioned and became available for
      production of rare isotopes. Currently, an electron cyclotron resonance ion
      source is used as a charge breeder for CARIBU beams. To further increase the
      intensity and improve the purity of neutron-rich ion beams accelerated by ATLAS,
      we are developing a high-efficiency charge breeder for CARIBU based on an
      electron beam ion source (EBIS). The CARIBU EBIS charge breeder will utilize the
      state-of-the-art EBIS technology recently developed at Brookhaven National
      Laboratory (BNL). The electron beam current density in the CARIBU EBIS trap will
      be significantly higher than that in existing operational charge-state breeders
      based on the EBIS concept. The design of the CARIBU EBIS charge breeder is nearly
      complete. Long-lead components of the EBIS such as a 6-T superconducting solenoid
      and an electron gun have been ordered with the delivery schedule in the fall of
      2011. Measurements of expected breeding efficiency using the BNL Test EBIS have
      been performed using a Cs(+) surface ionization ion source for external injection
      in pulsed mode. In these experiments we have achieved ~70% injection/extraction
      efficiency and breeding efficiency into the most abundant charge state of ~17%.

PMID- 22380244
TI  - Upgrade of the resonance ionization laser ion source at ISOLDE on-line isotope
      separation facility: new lasers and new ion beams.
AB  - The resonance ionization laser ion source (RILIS) produces beams for the majority
      of experiments at the ISOLDE on-line isotope separator. A substantial improvement
      in RILIS performance has been achieved through a series of upgrade steps:
      replacement of the copper vapor lasers by a Nd:YAG laser; replacement of the old
      homemade dye lasers by new commercial dye lasers; installation of a complementary
      Ti:Sapphire laser system. The combined dye and Ti:Sapphire laser system with
      harmonics is capable of generating beams at any wavelength in the range of 210
      950 nm. In total, isotopes of 31 different elements have been selectively laser
      ionized and separated at ISOLDE, including recently developed beams of samarium,
      praseodymium, polonium, and astatine.

PMID- 22380245
TI  - Laser ion source development at Holifield Radioactive Ion Beam Facility.
AB  - This report describes the efforts made to develop a resonant-ionization laser ion
      source based on tunable Ti:sapphire lasers for nuclear physics and astrophysics
      research at Holifield Radioactive Ion Beam Facility. Three Ti:sapphire lasers
      have been upgraded with individual pump lasers to eliminate laser power losses
      due to synchronization delays. Ionization schemes for 14 elements have been
      obtained. Off-line studies show that the overall efficiency of the laser ion
      source can be as high as 40%. TaC surface coatings have been investigated for
      minimizing surface and bulk trapping of the atoms of interest.

PMID- 22380246
TI  - Production of rare isotope beams at the Texas A&M University Cyclotron Institute.
AB  - The Cyclotron Institute at Texas A&M is currently configuring a scheme for the
      production of radioactive-ion beams that incorporates a light-ion guide and a
      heavy-ion guide coupled with an electron-cyclotron-resonance ion source
      constructed for charge-breeding. This scheme is part of an upgrade to the
      facility and is intended to produce radioactive beams suitable for injection into
      the K500 superconducting cyclotron. The current status of the project and details
      on the ion sources used in the project is presented.

PMID- 22380247
TI  - Prospects for advanced electron cyclotron resonance and electron beam ion source
      charge breeding methods for EURISOL.
AB  - As the most ambitious concept of isotope separation on line (ISOL) facility,
      EURISOL aims at producing unprecedented intensities of post-accelerated
      radioactive isotopes. Charge breeding, which transforms the charge state of
      radioactive beams from 1+ to an n+ charge state prior to post-acceleration, is a
      key technology which has to overcome the following challenges: high charge states
      for high energies, efficiency, rapidity and purity. On the roadmap to EURISOL, a
      dedicated R&D is being undertaken to push forward the frontiers of the present
      state-of-the-art techniques which use either electron cyclotron resonance or
      electron beam ion sources. We describe here the guidelines of this R&D.

PMID- 22380248
TI  - Off-line ionization tests using the surface and the plasma ion sources of the
      SPES project.
AB  - The development of new target ion source systems for the selective production of
      exotic species (SPES) facility is currently in progress at Legnaro National
      Laboratories. In this context, the study of ion sources and their performance in
      terms of ionization efficiency and transversal emittance is a crucial point in
      order to maximize the available yields, particularly for short-lived isotopes. In
      this work, preliminary off-line ionization efficiency and emittance measurements
      for the SPES surface and plasma ion sources are presented. The plasma source
      emittance measurements are supported by dedicated numerical calculations.

PMID- 22380249
TI  - Initial commissioning results with the NSCL Electron Beam Ion Trap.
AB  - The ReA reaccelerator is being added to the National Superconducting Cyclotron
      Laboratory (NSCL) fragmentation facility in order to provide exotic rare-isotope
      beams, not available at the Isotope Separation On-Line facilities, in the several
      MeV/u energy range. The first stage of the NSCL reaccelerator complex, consisting
      of an EBIT charge breeder, a room-temperature radiofrequency quadrupole (RFQ)
      accelerator, and superconducting linear accelerator modules, has been completed
      and is being put into operation. Commissioning of the EBIT has started by
      extracting charge-bred residual gas ions, ions created from a Ne gas jet directed
      across the EBIT's electron beam and ions captured from an external test ion
      source. Charge-bred ions from the Ne gas jet have been extracted as a pulse and
      accelerated through the RFQ and the two cryomodules.

PMID- 22380250
TI  - Beam injection improvement for electron cyclotron resonance charge breeders.
AB  - The injection of a 1+ beam into an electron cyclotron resonance (ECR) charge
      breeder is classically performed through a grounded tube placed on its axis at
      the injection side. This tube presents various disadvantages for the operation of
      an ECR charge breeder. First experiments without a grounded tube show a better
      use of the microwave power and a better charge breeding efficiency. The optical
      acceptance of the charge breeder without decelerating tube allows the injection
      of high intensity 1+ ion beams at high energy, allowing metals sputtering inside
      the ion source. The use of this method for refractory metallic ion beams
      production is evaluated.

PMID- 22380251
TI  - Wall-loss distribution of charge breeding ions in an electron cyclotron resonance
      ion source.
AB  - We investigated the ion-loss distribution on the sidewall of an electron
      cyclotron resonance (ECR) plasma chamber using the 18-GHz ECR charge breeder at
      the Tokai Radioactive Ion Accelerator Complex (TRIAC). Similarities and
      differences between the ion-loss distributions (longitudinal and azimuthal) of
      different ion species (i.e., radioactive (111)In(1+) and (140)Xe(1+) ions that
      are typical volatile and nonvolatile elements) was qualitatively discussed to
      understand the element dependence of the charge breeding efficiency. Especially,
      the similarities represent universal ion loss characteristics in an ECR charge
      breeder, which are different from the loss patterns of electrons on the ECRIS
      wall.

PMID- 22380252
TI  - Status of the SPIRAL I upgrade at GANIL.
AB  - The upgrade of the "Systeme de Production d'Ions Radioactifs en Ligne" phase I
      (SPIRAL I) installed at the "Grand Accelerateur National d'Ions Lourds" (GANIL)
      situated at Caen, France, is in progress and should be ready by 2014. In
      parallel, the first part of SPIRAL II facility is currently under construction.
      The global status of the upgrade is presented: goal, radioactive ion production
      systems, modification of the production cave and impact of the current safety re
      evaluation of GANIL.

PMID- 22380253
TI  - The on-line charge breeding program at TRIUMF's Ion Trap For Atomic and Nuclear
      Science for precision mass measurements.
AB  - TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN) constitutes the only
      high precision mass measurement setup coupled to a rare isotope facility capable
      of increasing the charge state of short-lived nuclides prior to the actual mass
      determination in a Penning trap. Recent developments around TITAN's charge
      breeder, the electron beam ion trap, form the basis for several successful
      experiments on radioactive isotopes with half-lives as low as 65 ms and in charge
      states as high as 22+.

PMID- 22380254
TI  - Charge breeding results and future prospects with electron cyclotron resonance
      ion source and electron beam ion source (invited).
AB  - The Californium Rare Ion Breeder Upgrade (CARIBU) of the Argonne National
      Laboratory ATLAS facility will provide low-energy and reaccelerated neutron-rich
      radioactive beams for the nuclear physics program. A 70 mCi (252)Cf source
      produces fission fragments which are thermalized and collected by a helium gas
      catcher into a low-energy particle beam with a charge of 1+ or 2+. An electron
      cyclotron resonance (ECR) ion source functions as a charge breeder in order to
      raise the ion charge sufficiently for acceleration in the ATLAS linac. The final
      CARIBU configuration will utilize a 1 Ci (252)Cf source to produce radioactive
      beams with intensities up to 10(6) ions/s for use in the ATLAS facility. The ECR
      charge breeder has been tested with stable beam injection and has achieved charge
      breeding efficiencies of 3.6% for (23)Na(8+), 15.6% for (84)Kr(17+), and 13.7%
      for (85)Rb(19+) with typical breeding times of 10 ms/charge state. For the first
      radioactive beams, a charge breeding efficiency of 11.7% has been achieved for
      (143)Cs(27+) and 14.7% for (143)Ba(27+). The project has been commissioned with a
      radioactive beam of (143)Ba(27+) accelerated to 6.1 MeV/u. In order to take
      advantage of its lower residual contamination, an EBIS charge breeder will
      replace the ECR charge breeder in the next two years. The advantages and
      disadvantages of the two techniques are compared taking into account the
      requirements of the next generation radioactive beam facilities.

PMID- 22380255
TI  - Recent developments of the ion sources at Tri University Meson Factory/Isotope
      Separator and ACcelerator Facility.
AB  - This paper describes the recent progresses concerning the on-line ion source at
      the Tri University Meson Factory/Isotope Separator and ACcelerator (TRIUMF/ISAC)
      Radioactive Ion-Beam Facility; description of the new design of the surface-ion
      source for improved stability of the beam intensity, description of the transport
      path to the east target station at ISAC, description of the new brazing
      techniques that solved recurrent problems with water leaks on the target/ion
      source assembly in the vacuum system, finally, recent developments concerning the
      Forced Electron Beam Induced Arc Discharge (FEBIAD) ion source are reported. In
      particular, a study on the effect of the plasma chamber volume on the ionization
      efficiency was completed.

PMID- 22380256
TI  - Status of the ion sources developments for the Spiral2 project at GANIL.
AB  - The SPIRAL 2 facility is now under construction and will deliver either stable or
      radioactive ion beams. First tests of nickel beam production have been performed
      at GANIL with a new version of the large capacity oven, and a calcium beam has
      been produced on the heavy ion low energy beam transport line of SPIRAL 2,
      installed at LPSC Grenoble. For the production of radioactive beams, several
      target/ion-source systems (TISSs) are under development at GANIL as the 2.45 GHz
      electron cyclotron resonance ion source, the surface ionization source, and the
      oven prototype for heating the uranium carbide target up to 2000  degrees C. The
      existing test bench has been upgraded for these developments and a new one,
      dedicated for the validation of the TISS before mounting in the production
      module, is under design. Results and current status of these activities are
      presented.

PMID- 22380257
TI  - Laser ion sources for radioactive beams (invited).
AB  - Resonant ionisation laser ion sources are nowadays extensively used, when
      available, at many leading on-line facilities. Moreover, new laser ion sources
      are now under development in most of the recent on-line facility projects under
      construction worldwide. This success is mainly due to the reliability, the
      ionization efficiency and the high purity that this type of source can achieve
      for the production of radioactive species and for a large range of chemical
      elements. Laser ion sources for radioactive beams gather many different systems
      such as dye laser or all-solid state titanium:sapphire laser systems, high or low
      repetition rates, hot cavities or gas cells, additional selectivity by using
      chemical techniques, or the LIST technique (laser ion source trap). In this
      paper, the physics of laser ion sources will be described with the current
      limitations and challenges for the future. An overview of the laser ion source
      facilities will be given, with an emphasis on the ongoing developments and
      perspectives on LIS.

PMID- 22380258
TI  - Effect of fast positive ions incident on caesiated plasma grid of negative ion
      source.
AB  - This paper describes the effect on negative ion formation on a caesiated surface
      of the backscattering of positive ions approaching it with energy of a few tens
      of eV. For a positive ion energy of 45 eV, the surface produced negative ion
      current density due to these fast positive ions is 12 times larger than that due
      to thermal atoms, thus dominating the negative ion surface production instead of
      the thermal atoms, as considered until now.

PMID- 22380259
TI  - First neutral beam injection experiments on KSTAR tokamak.
AB  - The first neutral beam (NB) injection system of the Korea Superconducting Tokamak
      Advanced Research (KSTAR) tokamak was partially completed in 2010 with only 1/3
      of its full design capability, and NB heating experiments were carried out during
      the 2010 KSTAR operation campaign. The ion source is composed of a JAEA bucket
      plasma generator and a KAERI large multi-aperture accelerator assembly, which is
      designed to deliver a 1.5 MW, NB power of deuterium at 95 keV. Before the beam
      injection experiments, discharge, and beam extraction characteristics of the ion
      source were investigated. The ion source has good beam optics in a broad range of
      beam perveance. The optimum perveance is 1.1-1.3 MUP, and the minimum beam
      divergence angle measured by the Doppler shift spectroscopy is 0.8 degrees . The
      ion species ratio is D(+):D(2)(+):D(3)(+) = 75:20:5 at beam current density of 85
      mA/cm(2). The arc efficiency is more than 1.0 A/kW. In the 2010 KSTAR campaign, a
      deuterium NB power of 0.7-1.5 MW was successfully injected into the KSTAR plasma
      with a beam energy of 70-90 keV. L-H transitions were observed within a wide
      range of beam powers relative to a threshold value. The edge pedestal formation
      in the T(i) and T(e) profiles was verified through CES and electron cyclotron
      emission diagnostics. In every deuterium NB injection, a burst of D-D neutrons
      was recorded, and increases in the ion temperature and plasma stored energy were
      found.

PMID- 22380260
TI  - Diagnostics of the ITER neutral beam test facility.
AB  - The ITER heating neutral beam (HNB) injector, based on negative ions accelerated
      at 1 MV, will be tested and optimized in the SPIDER source and MITICA full
      injector prototypes, using a set of diagnostics not available on the ITER HNB.
      The RF source, where the H(-)/D(-) production is enhanced by cesium evaporation,
      will be monitored with thermocouples, electrostatic probes, optical emission
      spectroscopy, cavity ring down, and laser absorption spectroscopy. The beam is
      analyzed by cooling water calorimetry, a short pulse instrumented calorimeter,
      beam emission spectroscopy, visible tomography, and neutron imaging. Design of
      the diagnostic systems is presented.

PMID- 22380261
TI  - The development of the radio frequency driven negative ion source for neutral
      beam injectors (invited).
AB  - Large and powerful negative hydrogen ion sources are required for the neutral
      beam injection (NBI) systems of future fusion devices. Simplicity and maintenance
      free operation favors RF sources, which are developed intensively at the Max
      Planck-Institut fur Plasmaphysik (IPP) since many years. The negative hydrogen
      ions are generated by caesium-enhanced surface conversion of atoms and positive
      ions on the plasma grid surface. With a small scale prototype the required high
      ion current density and the low fraction of co-extracted electrons at low
      pressure as well as stable pulses up to 1 h could be demonstrated. The modular
      design allows extension to large source dimensions. This has led to the decision
      to choose RF sources for the NBI of the international fusion reactor, ITER. As an
      intermediate step towards the full size ITER source at IPP, the development will
      be continued with a half-size source on the new ELISE testbed. This will enable
      to gain experience for the first time with negative hydrogen ion beams from RF
      sources of these dimensions.

PMID- 22380262
TI  - Generation of solid-density ultraintense ion beams by a picosecond laser pulse of
      circular polarization.
AB  - This contribution reports particle-in-cell numerical studies of deuteron beam
      acceleration by a picosecond laser pulse of circular polarization. The effect of
      laser wavelength lambda and the I(L)lambda(2) product (I(L) is laser intensity)
      on the ion beam parameters is investigated. It is shown that at the I(L)lambda(2)
      product fixed, the beam parameters (<E(i)>, I(i), F(i)) as well as the laser-ions
      energy conversion efficiency quickly increase with a decrease in the laser
      wavelength and the best results are achieved for a KrF laser (lambda = 0.248
      MUm). In particular, a 2-ps KrF laser pulse of I(L)lambda(2) ~ 2 * 10(20) Wcm(-2)
      MUm(2) interacting with a 10-MUm deuteron target produces a quasi-monoenergetic,
      solid-density deuteron beam of parameters approaching those required for inertial
      confinement fusion fast ignition.

PMID- 22380263
TI  - A close-coupling multi-antenna type radio frequency driven ion source.
AB  - A newly close coupling multi-antenna type radio frequency driven ion source is
      tested for the purpose of essentially improving plasma coupling on the basis of
      our old type ion source, which reuses a NNBI (negative ion source for neutral
      beam injection) ion source used in 1/5th scale of the Large Helical Device NNBI.
      The ion source and the antenna structure are described, and the efficient plasma
      production in terms of the positive ion saturation current (the current density)
      is studied. The source is made of a metal-walled plasma chamber which is
      desirable from the point of view of the structural toughness for fusion and
      industrial application, etc. At around 160 kW of rf input power, the ion
      saturation current density successfully reaches the 5 A/cm(2) level with a gas
      pressure of 0.6-2 Pa in hydrogen for 10 ms pulse duration. The rf power
      efficiency of the plasma production with a close coupling configuration of the
      antenna is improved substantially compared to that with the previous antenna unit
      in the old type ion source. The power efficiency is assessed as competing with
      that of other types of sources.

PMID- 22380264
TI  - Concepts for the magnetic design of the MITICA neutral beam test facility ion
      accelerator.
AB  - The megavolt ITER injector concept advancement neutral injector test facility
      will be constituted by a RF-driven negative ion source and by an electrostatic
      Accelerator, designed to produce a negative Ion with a specific energy up to 1
      MeV. The beam is then neutralized in order to obtain a focused 17 MW neutral
      beam. The magnetic configuration inside the accelerator is of crucial importance
      for the achievement of a good beam efficiency, with the early deflection of the
      co-extracted and stripped electrons, and also of the required beam optic quality,
      with the correction of undesired ion beamlet deflections. Several alternative
      magnetic design concepts have been considered, comparing in detail the magnetic
      and beam optics simulation results, evidencing the advantages and drawbacks of
      each solution both from the physics and engineering point of view.

PMID- 22380265
TI  - Progress in the MITICA beam source design.
AB  - In the framework of the development of the ITER neutral beam (NB) system, a test
      facility is planned to be built in Padova. A full size prototype of the ITER
      heating NB injector (MITICA) shall be built and tested at full beam power (17 MW)
      as per ITER requirements. The design of the MITICA beam source has further
      progressed following updated optimization and overall integration criteria. In
      the paper, the major design choices and revisions are presented, together with
      some results of numerical analyses carried out in order to assess the
      electrostatic and thermo-mechanical behaviour of the source.

PMID- 22380266
TI  - Sheath structure in negative ion sources for fusion (invited).
AB  - In fusion negative ion sources, the negative ions are formed on the caesiated
      plasma grid predominantly by hydrogen atoms from the plasma. The space charge of
      the negative ions leaving the wall is not fully compensated by incoming positive
      ions and at high enough emission a virtual cathode is formed. This virtual
      cathode limits the flux of negative ions transported across the sheath to the
      plasma. A 1D collisionless model of the sheath is presented taking into account
      the virtual cathode. The model will be applied to examples of the ion source
      operation. Extension of the model to the bulk plasma shows good agreement with
      experimental data. A possible role for fast ions is discussed.

PMID- 22380267
TI  - Cesium dynamics in long pulse operation of negative hydrogen ion sources for
      fusion.
AB  - Large scale negative hydrogen ion sources operating stable for 1 h (cw mode) are
      required for the neutral beam heating system of the fusion experiment ITER. The
      formation of negative hydrogen ions relies on the surface effect for which cesium
      is evaporated into the source. In order to monitor the cesium dynamics the laser
      absorption spectroscopy technique is applied to the long pulse test facility
      MANITU. In the vacuum phase, without plasma operation the evaporation of cesium
      and the built-up of the cesium in the source are measured. Typical neutral cesium
      densities are 10(15) m(-3). During plasma operation and after the plasma phase a
      high cesium dynamics is observed, showing also depletion of cesium during long
      pulses with low cesium amount. The co-extracted electron current decreases with
      the cesium amount to a certain level whereas the ion current indicates an optimum
      density range.

PMID- 22380268
TI  - Monoenergetic proton emission from nuclear reaction induced by high intensity
      laser-generated plasma.
AB  - A 10(16) W/cm(2) Asterix laser pulse intensity, 1315 nm at the fundamental
      frequency, 300 ps pulse duration, was employed at PALS laboratory of Prague, to
      irradiate thick and thin primary CD(2) targets placed inside a high vacuum
      chamber. The laser irradiation produces non-equilibrium plasma with deutons and
      carbon ions emission with energy of up to about 4 MeV per charge state, as
      measured by time-of-flight (TOF) techniques by using ion collectors and silicon
      carbide detectors. Accelerated deutons may induce high D-D cross section for
      fusion processes generating 3 MeV protons and 2.5 MeV neutrons, as measured by
      TOF analyses. In order to increase the mono-energetic proton yield, secondary
      CD(2) targets can be employed to be irradiated by the plasma-accelerated deutons.
      Experiments demonstrated that high intensity laser pulses can be employed to
      promote nuclear reactions from which characteristic ion streams may be developed.
      Results open new scenario for applications of laser-generated plasma to the
      fields of ion sources and ion accelerators.

PMID- 22380269
TI  - New ion source for KSTAR neutral beam injection system.
AB  - The neutral beam injection system (NBI-1) of the KSTAR tokamak can accommodate
      three ion sources; however, it is currently equipped with only one prototype ion
      source. In the 2010 and 2011 KSTAR campaigns, this ion source supplied deuterium
      neutral beam power of 0.7-1.6 MW to the KSTAR plasma with a beam energy of 70-100
      keV. A new ion source will be prepared for the 2012 KSTAR campaign with a much
      advanced performance compared with the previous one. The newly designed ion
      source has a very large transparency (~56%) without deteriorating the beam
      optics, which is designed to deliver a 2 MW injection power of deuterium beams at
      100 keV. The plasma generator of the ion source is of a horizontally cusped
      bucket type, and the whole inner wall, except the cathode filaments and plasma
      grid side, functions as an anode. The accelerator assembly consists of four multi
      circular aperture grids made of copper and four electrode flanges made of
      aluminum alloy. The electrodes are insulated using PEEK. The ion source will be
      completed and tested in 2011.

PMID- 22380270
TI  - Electron density measurement of cesium seeded negative ion source by surface wave
      probe.
AB  - Electron density measurements of a large-scaled negative ion source were carried
      out with a surface wave probe. By comparison of the electron densities determined
      with the surface wave probe and a Langmuir probe, it was confirmed that the
      surface wave probe is highly available for diagnostic of the electron density in
      H(-) ion sources. In addition, it was found that the ratio of the electron
      density to the H(-) ion density dramatically decreases with increase of a bias
      voltage and the H(-) ions become dominant negative particles at the bias voltage
      of more than 6 V.

PMID- 22380271
TI  - Commissioning of heating neutral beams for COMPASS-D tokamak.
AB  - Two neutral beam injectors have been developed for plasma heating on COMPASS-D
      tokamak (Institute of Plasma Physics, Prague). The 4-electrodes multihole ion
      optical system with beam focusing was chosen to provide the low divergence 300 kW
      power in both deuterium and hydrogen atoms. The accelerating voltage is 40 kV at
      extracted ion current up to 15 A. The power supply system provides the continuous
      and modulated mode of the beam injection at a maximal pulse length 300 ms. The
      optimal arrangement of the cryopanels and the beam duct elements provides
      sufficiently short-length beamline which reduces the beam losses. The evolution
      of the impurities and molecular fraction content is studied in the process of the
      high voltage conditioning of the newly made ion sources. Two injectors of the
      same type have been successfully tested and are ready for operation at tokamak in
      IPP, Prague.

PMID- 22380272
TI  - Development of a He- and He0 beam source for alpha particle measurement in a
      burning plasma.
AB  - Proof of principle experiments of neutral helium beam production for alpha
      particle diagnostics was carried out on a test stand. Negative helium ions were
      produced in the Li charge exchange cell, in which stable and long time operation
      was possible. He(-) beam was accelerated to 157 keV. Finally, He(0) beam was
      successfully produced after the flight in the drift-tube through the auto
      electron-detachment process from He(-) to He(0). A neutral beam detector using a
      pyroelectric device was also developed to measure He(0) beam intensity. The
      metastable component in the neutral helium beam was found to be less than 2%.

PMID- 22380273
TI  - Spatial distribution of the charged particles and potentials during beam
      extraction in a negative-ion source.
AB  - We report on the characteristics of the electronegative plasma in a large-scale
      hydrogen negative ion (H(-)) source. The measurement has been made with a time
      resolved Langmuir probe installed in the beam extraction region. The H(-) density
      is monitored with a cavity ring-down system to identify the electrons in the
      negative charges. The electron-saturation current decreases rapidly after
      starting to seed Cs, and ion-ion plasma is observed in the extraction region. The
      H(-) density steps down during the beam extraction and the electron density jumps
      up correspondingly. The time integral of the decreasing H(-) charge density
      agrees well with the electron charge collected with the probe. The agreement of
      the charges is interpreted to indicate that the H(-) density decreasing at the
      beam extraction is compensated by the electrons diffusing from the driver region.
      In the plasmas with very low electron density, the pre-sheath of the extraction
      field penetrates deeply inside the plasmas. That is because the shielding length
      in those plasmas is longer than that in the usual electron-ion plasmas, and
      furthermore the electrons are suppressed to diffuse to the extraction region due
      to the strong magnetic field.

PMID- 22380274
TI  - Vacuum insulation of the high energy negative ion source for fusion application.
AB  - Vacuum insulation on a large size negative ion accelerator with multiple
      extraction apertures and acceleration grids for fusion application was
      experimentally examined and designed. In the experiment, vacuum insulation
      characteristics were investigated in the JT-60 negative ion source with >1000
      apertures on the grid with the surface area of ~2 m(2). The sustainable voltages
      varied with a square root of the gap lengths between the grids, and decreased
      with number of the apertures and with the surface area of the grids. Based on the
      obtained results, the JT-60SA (super advanced) negative ion source is designed to
      produce 22 A, 500 keV D(-) ion beams for 100 s.

PMID- 22380275
TI  - Multiple delivery cesium oven system for negative ion sources.
AB  - Distribution of cesium in large negative ion beam sources to be operational in
      ITER, is presently based on the use of three or more cesium ovens, which operate
      simultaneously and are controlled remotely. However, use of multiple Cs ovens
      simultaneously is likely to pose difficulties in operation and maintenance of the
      ovens. An alternate method of Cs delivery, based on a single oven distribution
      system is proposed as one which could reduce the need of simultaneous operation
      of many ovens. A proof of principle experiment verifying the concept of a
      multinozzle distributor based Cs oven has been carried out at Institute for
      Plasma Research. It is also observed that the Cs flux is not controlled by Cs
      reservoir temperature after few hours of operation but by the temperature of the
      distributor which starts behaving as a Cs reservoir.

PMID- 22380276
TI  - Beam optics in a MeV-class multi-aperture multi-grid accelerator for the ITER
      neutral beam injector.
AB  - In a multi-aperture multi-grid accelerator of the ITER neutral beam injector, the
      beamlets are deflected due to space charge repulsion between beamlets and beam
      groups, and also due to magnetic field. Moreover, the beamlet deflection is
      influenced by electric field distortion generated by grid support structure. Such
      complicated beamlet deflections and the compensations have been examined
      utilizing a three-dimensional beam analysis. The space charge repulsion and the
      influence by the grid support structure were studied in a 1/4 model of the
      accelerator including 320 beamlets. Beamlet deflection due to the magnetic field
      was studied by a single beamlet model. As the results, compensation methods of
      the beamlet deflection were designed, so as to utilize a metal bar (so-called
      field shaping plate) of 1 mm thick beneath the electron suppression grid (ESG),
      and an aperture offset of 1 mm in the ESG.

PMID- 22380277
TI  - Extraction of a strongly focusing He+ beam from three-stage concave electrodes
      for alpha particle measurement system in ITER.
AB  - A strongly focusing He(+) ion beam source equipped with concave multi-aperture
      electrodes was developed for production of He(-) through a charge exchange cell.
      The beam was extracted at a voltage less than 20 kV from 301 apertures
      distributed in an area of 100 mm phi, and focused at 750 mm distance. The beam
      current and the beam size of 2 A and 20 mm in diameter, respectively, were
      achieved with an arc power less than 10 kW. The optimum perveance was obtained at
      0.02 A/kV(1.5) at the beam energy less than 20 keV which is suitable for the
      conversion to He(-) in an alkali vapor cell.

PMID- 22380278
TI  - Voltage holding study of 1 MeV accelerator for ITER neutral beam injector.
AB  - Voltage holding test on MeV accelerator indicated that sustainable voltage was a
      half of that of ideal quasi-Rogowski electrode. It was suggested that the
      emission of the clumps is enhanced by a local electric field concentration, which
      leads to discharge initiation at lower voltage. To reduce the electric field
      concentration in the MeV accelerator, gaps between the grid supports were
      expanded and curvature radii at the support corners were increased. After the
      modifications, the accelerator succeeded in sustaining -1 MV in vacuum without
      beam acceleration. However, the beam energy was still limited at a level of 900
      keV with a beam current density of 150 A/m(2) (346 mA) where the 3 * 5 apertures
      were used. Measurement of the beam profile revealed that deflection of the H(-)
      ions was large and a part of the H(-) ions was intercepted at the acceleration
      grid. This causes high heat load on the grids and the breakdowns during beam
      acceleration. To suppress the direct interception, new grid system was designed
      with proper aperture displacement based on a 3D beam trajectory analysis. As the
      result, the beam deflection was compensated and the voltage holding during the
      beam acceleration was improved. Beam parameter of the MeV accelerator was
      increased to 980 keV, 185 A/m(2) (427 mA), which is close to the requirement of
      ITER accelerator (1 MeV, 200 A/m(2)).

PMID- 22380279
TI  - H- beam extraction from a cesium seeded field effect transistor based radio
      frequency negative hydrogen ion source.
AB  - H(-) beam was successfully extracted from a cesium seeded ion source operated
      using a field effect transistor inverter power supply as a radio frequency (RF)
      wave source. High density hydrogen plasma more than 10(19) m(-3) was obtained
      using an external type antenna with RF frequency of lower than 0.5 MHz. The
      source was isolated by an isolation transformer and H(-) ion beam was extracted
      from a single aperture. Acceleration current and extraction current increased
      with the increase of extraction voltage. Addition of a small amount of cesium
      vapor into the source enhanced the currents.

PMID- 22380280
TI  - Low-energy, high-current, ion source with cold electron emitter.
AB  - An ion source based on a two-stage discharge with electron injection from a cold
      emitter is presented. The first stage is the emitter itself, and the second stage
      provides acceleration of injected electrons for gas ionization and formation of
      ion flow (<20 eV, 5 A dc). The ion accelerating system is gridless; acceleration
      is accomplished by an electric field in the discharge plasma within an axially
      symmetric, diverging, magnetic field. The hollow cathode electron emitter
      utilizes an arc discharge with cathode spots hidden inside the cathode cavity.
      Selection of the appropriate emitter material provides a very low erosion rate
      and long lifetime.

PMID- 22380281
TI  - Shot-to-shot reproducibility in the emission of fast highly charged metal ions
      from a laser ion source.
AB  - The generation of fast highly charged metal ions with the use of the sub
      nanosecond Prague Asterix Laser System, operated at a fundamental wavelength of
      1315 nm, is reported. Particular attention is paid to shot-to-shot
      reproducibility in the ion emission. Au and Pd targets were exposed to
      intensities up to 5 * 10(16) W/cm(2). Above the laser intensity threshold of ~3 *
      10(14) W/cm(2) the plasma is generated in a form of irregular bursts. The maximum
      energy of protons constituting the leading edge of the fastest burst reaches a
      value up to 1 MeV. The fast ions in the following bursts have energy gradually
      decreasing with the increasing burst number, namely, from a value of about 0.5
      MeV/charge regardless of the atomic number and mass of the ionized species.

PMID- 22380282
TI  - Status of the laser ion source at IMP.
AB  - A laser (Nd:YAG laser, 3 J, 1064 nm, 8-10 ns) ion source has been built and under
      development at IMP to provide pulsed high-charge-state heavy ion beams to a radio
      frequency quadrupole (RFQ) for upgrading the IMP accelerators with a new low
      energy beam injector. The laser ion source currently operates in a direct plasma
      injection scheme to inject the high charge state ions produced from a solid
      target into the RFQ. The maximum power density on the target was about 8.4 *
      10(12) W/cm(2). The preliminary experimental results will be presented and
      discussed in this paper.

PMID- 22380283
TI  - Optimizing a microwave gas ion source for continuous-flow accelerator mass
      spectrometry.
AB  - A 2.45 GHz microwave ion source coupled with a magnesium charge exchange canal (C
      * C) has been successfully adapted to a large acceptance radiocarbon accelerator
      mass spectrometry system at the National Ocean Sciences Accelerator Mass
      Spectrometry (AMS) Facility, Woods Hole Oceanographic Institution. CO(2) samples
      from various preparation sources are injected into the source through a glass
      capillary at 370 MUl/min. Routine system parameters are about 120-140 MUA of
      negative (12)C current after the C * C, leading to about 400 (14)C counts per
      second for a modern sample and implying a system efficiency of 0.2%. While these
      parameters already allow us to perform high-quality AMS analyses on large
      samples, we are working on ways to improve the output of the ion source regarding
      emittance and efficiency. Modeling calculations suggest modifications in the
      extraction triode geometry, shape, and size of the plasma chamber could improve
      emittance and, hence, ion transport efficiency. Results of experimental tests of
      these modifications are presented.

PMID- 22380284
TI  - Laser produced streams of Ge ions accelerated and optimized in the electric
      fields for implantation into SiO2 substrates.
AB  - Ge crystals were prepared by means of laser-induced ion implantation technique. A
      Nd:YAG pulsed laser (repetition rate: 10 Hz; pulse duration: 3.5 ns; pulse
      energy: ~0.5 J) was used both as an ion source and to carry out the ablation
      processes. The optimization of the laser-generated ion beam parameters in a broad
      energy and current density range has been obtained controlling the electrostatic
      field parameters. Numerical simulations of the focusing system, performed
      adopting an OPERA 3D code, and an investigation of the ion characteristics, using
      the ion time-of-flight method, have allowed to optimize the preparation
      parameters. The structural properties of the samples were investigated by means
      of x-ray photoelectron, micro-Raman spectroscopies, and scanning electron
      microscopy techniques. Experimental results show that, by appropriately varying
      the ion implantation parameters and by a post-preparation annealing treatment, it
      is possible to achieve the development of a micrometer-sized crystalline Ge phase
      and/or an amorphous one.

PMID- 22380285
TI  - New laser setup for the selective isotope production and investigation in a laser
      ion source at the IRIS (Investigation of Radioactive Isotopes on
      Synchrocyclotron) facility.
AB  - New laser installation for the resonance ionization spectroscopy in a laser ion
      source and for rare isotope production has been recently put into operation at
      the IRIS (Investigation of Radioactive Isotopes on Synchrocyclotron) facility
      (Petersburg Nuclear Physics Institute, Gatchina). This is a significant
      improvement of a previous target-laser ion source device of the IRIS mass
      separator, working on-line with 1 GeV proton beam of PNPI (Petersburg Nuclear
      Physics Institute) synchrocyclotron. It makes possible for us to get the
      isobarically clean radioactive isotope beams of a great number of chemical
      elements. New laser setup provides the two- or three-resonance step ionization in
      the range of wavelength of 265-850 nm. The first results obtained at the laser
      setup for Tl isotopes are presented.

PMID- 22380286
TI  - New methods for high current fast ion beam production by laser-driven
      acceleration.
AB  - An overview of the last experimental campaigns on laser-driven ion acceleration
      performed at the PALS facility in Prague is given. Both the 2 TW, sub-nanosecond
      iodine laser system and the 20 TW, femtosecond Ti:sapphire laser, recently
      installed at PALS, are used along our experiments performed in the intensity
      range 10(16)-10(19) W/cm(2). The main goal of our studies was to generate high
      energy, high current ion streams at relatively low laser intensities. The
      discussed experimental investigations show promising results in terms of maximum
      ion energy and current density, which make the laser-accelerated ion beams a
      candidate for new-generation ion sources to be employed in medicine, nuclear
      physics, matter physics, and industry.

PMID- 22380287
TI  - Laser ion source with a double pulse laser system.
AB  - To extend an ion beam pulse of a laser ion source, multiple laser shots could be
      used. To check the feasibility of this idea, we tested double laser irradiations
      on an iron target. When the interval of the two laser shots is longer than 10
      MUs, the obtained ion current profile was expressed as a sum of two individual
      expanded laser plasmas. However, if the interval is too close, a current
      reduction was observed. This technique can be effectively applied to low charge
      state ion production.

PMID- 22380288
TI  - Novel methods for improvement of a Penning ion source for neutron generator
      applications.
AB  - Penning ion source performance for neutron generator applications is
      characterized by the atomic ion fraction and beam current density, providing two
      paths by which source performance can be improved for increased neutron yields.
      We have fabricated a Penning ion source to investigate novel methods for
      improving source performance, including optimization of wall materials and
      electrode geometry, advanced magnetic confinement, and integration of field
      emitter arrays for electron injection. Effects of several electrode geometries on
      discharge characteristics and extracted ion current were studied. Additional
      magnetic confinement resulted in a factor of two increase in beam current
      density. First results indicate unchanged proton fraction and increased beam
      current density due to electron injection from carbon nanofiber arrays.

PMID- 22380289
TI  - Proton emission from a laser ion source.
AB  - At intensities of the order of 10(10) W/cm(2), ns pulsed lasers can be employed
      to ablate solid bulk targets in order to produce high emission of ions at
      different charge state and kinetic energy. A special interest is devoted to the
      production of protons with controllable energy and current from a roto
      translating target irradiated in repetition rate at 1-10 Hz by a Nd:Yag pulsed
      laser beam. Different hydrogenated targets based on polymers and hydrates were
      irradiated in high vacuum. Special nanostrucutres can be embedded in the polymers
      in order to modify the laser absorption properties and the amount of protons to
      be accelerated in the plasma. For example, carbon nanotubes may increase the
      laser absorption and the hydrogen absorption to generate high proton yields from
      the plasma. Metallic nanostrucutres may increase the electron density of the
      plasma and the kinetic energy of the accelerated protons. Ion collectors, ion
      energy analyzer, and mass spectrometers, used in time-of-flight configuration,
      were employed to characterize the ion beam properties. A comparison with
      traditional proton ion source is presented and discussed.

PMID- 22380290
TI  - Molecular phosphorus ion source for semiconductor technology.
AB  - This paper presents results on the generation of molecular phosphorus ion beams
      in a hot filament ion source. Solid red phosphorous is evaporated mainly as tetra
      atomic molecules up to a temperature of 800 degrees C. Thus, one of the main
      conditions for producing maximum P(4)(+) fraction in the beam is to keep the
      temperature of the phosphorous oven, the steam line and the discharge chamber
      walls no greater than 800 degrees C. The prior version of our ion source was
      equipped with a discharge chamber cooling system. The modified source ensured a
      P(4)(+) ion beam current greater than 30% of the total beam current.

PMID- 22380291
TI  - A compact neutron generator using a field ionization source.
AB  - Field ionization as a means to create ions for compact and rugged neutron sources
      is pursued. Arrays of carbon nano-fibers promise the high field-enhancement
      factors required for efficient field ionization. We report on the fabrication of
      arrays of field emitters with a density up to 10(6) tips/cm(2) and measure their
      performance characteristics using electron field emission. The critical issue of
      uniformity is discussed, as are efforts towards coating the nano-fibers to
      enhance their lifetime and surface properties.

PMID- 22380292
TI  - Brightness enhancement of plasma ion source by utilizing anode spot for nano
      applications.
AB  - Anode spots are known as additional discharges on positively biased electrode
      immersed in plasmas. The anode spot plasma ion source (ASPIS) has been
      investigated as a high brightness ion source for nano applications such as
      focused ion beam (FIB) and nano medium energy ion scattering (nano-MEIS). The
      generation of anode spot is found to enhance brightness of ion beam since the
      anode spot increases plasma density near the extraction aperture. Brightness of
      the ASPIS has been estimated from measurement of emittance for total ion beam
      extracted through sub-mm aperture. The ASPIS is installed to the FIB system.
      Currents and diameters of the focused beams with/without anode spot are measured
      and compared. As the anode spot is turned on, the enhancement of beam current is
      observed at fixed diameter of the focused ion beam. Consequently, the brightness
      of the focused ion beam is enhanced as well. For argon ion beam, the maximum
      normalized brightness of 12,300 A/m(2) SrV is acquired. The ASPIS is applied to
      nano-MEIS as well. The ASPIS is found to increase the beam current density and
      the power efficiency of the ion source for nano-MEIS. From the present study, it
      is shown that the ASPIS can enhance the performance of devices for nano
      applications.

PMID- 22380293
TI  - Study on monatomic fraction improvement with alumina layer on metal electrode in
      hydrogen plasma ion source.
AB  - A high monatomic beam fraction is an important factor in a hydrogen ion source to
      increase the application efficiency. The monatomic fraction of hydrogen plasmas
      with different plasma electrode materials is measured in a helicon plasma ion
      source, and aluminum shows the highest value compared to that with the other
      metals such as copper and molybdenum. Formation of an aluminum oxide layer on the
      aluminum electrode is determined by XPS analysis, and the alumina layer is
      verified as the high monatomic fraction. Both experiments and numerical
      simulations conclude that a low surface recombination coefficient of the alumina
      layer on the plasma electrode is one of the most important parameters for
      increasing the monatomic fraction in hydrogen plasma ion sources.

PMID- 22380294
TI  - Proton emission from thin hydrogenated targets irradiated by laser pulses at
      10(16) W/cm2.
AB  - The iodine laser at PALS Laboratory in Prague, operating at 1315 nm fundamental
      harmonics and at 300 ps FWHM pulse length, is employed to irradiate thin
      hydrogenated targets placed in vacuum at intensities on the order of 10(16)
      W/cm(2). The laser-generated plasma is investigated in terms of proton and ion
      emission in the forward and backward directions. The time-of-flight technique,
      using ion collectors and semiconductor detectors, is used to measure the ion
      currents and the corresponding velocities and energies. Thomson parabola
      spectrometer is employed to separate the contribution of the ion emission from
      single laser shots. A particular attention is given to the proton production in
      terms of the maximum energy, emission yield, and angular distribution as a
      function of the laser energy, focal position, target thickness, and composition.
      Metallic and polymeric targets allow to generate protons with large energy range
      and different yield, depending on the laser, target composition, and target
      geometry properties.

PMID- 22380295
TI  - Beam current enhancement of microwave plasma ion source utilizing double-port
      rectangular cavity resonator.
AB  - Microwave plasma ion source with rectangular cavity resonator has been examined
      to improve ion beam current by changing wave launcher type from single-port to
      double-port. The cavity resonators with double-port and single-port wave
      launchers are designed to get resonance effect at TE-103 mode and TE-102 mode,
      respectively. In order to confirm that the cavities are acting as resonator, the
      microwave power for breakdown is measured and compared with the E-field strength
      estimated from the HFSS (High Frequency Structure Simulator) simulation. Langmuir
      probe measurements show that double-port cavity enhances central density of
      plasma ion source by modifying non-uniform plasma density profile of the single
      port cavity. Correspondingly, beam current from the plasma ion source utilizing
      the double-port resonator is measured to be higher than that utilizing single
      port resonator. Moreover, the enhancement in plasma density and ion beam current
      utilizing the double-port resonator is more pronounced as higher microwave power
      applied to the plasma ion source. Therefore, the rectangular cavity resonator
      utilizing the double-port is expected to enhance the performance of plasma ion
      source in terms of ion beam extraction.

PMID- 22380296
TI  - Studies for aluminum photoionization in hot cavity for the selective production
      of exotic species project.
AB  - Selective production of exotic species (SPES) is an ISOL-based accelerator
      facility that will be built in the Legnaro INFN Laboratory (Italy), intended to
      provide an intense neutron-rich radioactive ion beams obtained by proton induced
      fission of an uranium carbide target. Beside this main target, a silicon carbide
      (SiC) target will the first to be used to deliver some p-rich beams. This target
      will validate also the functionality of the SPES facility with aluminum beam as
      result of hitting SiC target with protons. In the past off-line studies on laser
      photoionization of aluminum have performed in Pavia Spectroscopy Laboratory and
      in Laboratori Nazionali di Legnaro where, recently, a XeCl excimer laser was
      installed in order to test the laser ionization in the SPES hot cavity. Results
      are promising to justify further studies with this technique, aiming a better
      characterization of the SPES ion extraction capability under laser
      photoionization.

PMID- 22380297
TI  - A study of H+ production using metal hydride and other compounds by means of
      laser ion source.
AB  - A laser ion source can provide wide variety of ion beams from solid target
      materials, however, it has been difficult to create proton beam efficiently. We
      examined capability of proton production using beeswax, polyethylene, and metal
      hydrides (MgH(2) and ZrH(2)) as target materials. The results showed that beeswax
      and polyethylene could not be used to produce protons because these targets are
      transparent to the laser wavelength of 1064 nm. On the other hand, the metal
      hydrides could supply protons. Although the obtained particle numbers of protons
      were less than those of the metal ions, the metal hydrides could be used as a
      target for proton laser ion source.

PMID- 22380298
TI  - Laser ion source with solenoid for Brookhaven National Laboratory-electron beam
      ion source.
AB  - The electron beam ion source (EBIS) preinjector at Brookhaven National Laboratory
      (BNL) is a new heavy ion-preinjector for relativistic heavy ion collider (RHIC)
      and NASA Space Radiation Laboratory (NSRL). Laser ion source (LIS) is a primary
      ion source provider for the BNL-EBIS. LIS with solenoid at the plasma drift
      section can realize the low peak current (~100 MUA) with high charge (~10 nC)
      which is the BNL-EBIS requirement. The gap between two solenoids does not cause
      serious plasma current decay, which helps us to make up the BNL-EBIS beamline.

PMID- 22380299
TI  - Transport of intense ion beams and space charge compensation issues in low energy
      beam lines (invited).
AB  - Over the last few years, the interest of the international scientific community
      for high power accelerators in the megawatt range has been increasing. For such
      machines, the ion source has to deliver a beam intensity that ranges from several
      tens up to a hundred of mA. One of the major challenges is to extract and
      transport the beam while minimizing the emittance growth and optimizing its
      injection into the radio frequency quadrupole. Consequently, it is crucial to
      perform precise simulations and cautious design of the low energy beam transport
      (LEBT) line. In particular, the beam dynamics calculations have to take into
      account not only the space charge effects but also the space charge compensation
      of the beam induced by ionization of the residual gas. The physical phenomena
      occurring in a high intensity LEBT and their possible effects on the beam are
      presented, with a particular emphasis on space charge compensation. Then, beam
      transport issues in different kind of LEBTs are briefly reviewed. The SOLMAXP
      particle-in-cell code dedicated to the modeling of the transport of charge
      particles under a space charge compensation regime is described. Finally, beam
      dynamics simulations results obtained with SOLMAXP are presented in the case of
      international fusion materials irradiation facility injector.

PMID- 22380300
TI  - Comparison between off-resonance and electron Bernstein waves heating regime in a
      microwave discharge ion source.
AB  - A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del
      Sud of INFN, Catania has been used to compare the traditional electron cyclotron
      resonance (ECR) heating with an innovative mechanisms of plasma ignition based on
      the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma
      electromagnetic-to-electrostatic wave conversion and they are absorbed by the
      plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at
      particular frequencies enabled us to reach densities much larger than the cutoff
      ones. Evidences of EBW generation and absorption together with X-ray emissions
      due to high energy electrons will be shown. A characterization of the discharge
      heating process in MDISs as a generalization of the ECR heating mechanism by
      means of ray tracing will be shown in order to highlight the fundamental physical
      differences between ECR and EBW heating.

PMID- 22380301
TI  - Target normal sheath acceleration analytical modeling, comparative study and
      developments.
AB  - Ultra-intense laser interaction with solid targets appears to be an extremely
      promising technique to accelerate ions up to several MeV, producing beams that
      exhibit interesting properties for many foreseen applications. Nowadays, most of
      all the published experimental results can be theoretically explained in the
      framework of the target normal sheath acceleration (TNSA) mechanism proposed by
      Wilks et al. [Phys. Plasmas 8(2), 542 (2001)]. As an alternative to numerical
      simulation various analytical or semi-analytical TNSA models have been published
      in the latest years, each of them trying to provide predictions for some of the
      ion beam features, given the initial laser and target parameters. However, the
      problem of developing a reliable model for the TNSA process is still open, which
      is why the purpose of this work is to enlighten the present situation of TNSA
      modeling and experimental results, by means of a quantitative comparison between
      measurements and theoretical predictions of the maximum ion energy. Moreover, in
      the light of such an analysis, some indications for the future development of the
      model proposed by Passoni and Lontano [Phys. Plasmas 13(4), 042102 (2006)] are
      then presented.

PMID- 22380302
TI  - Models of radiofrequency coupling for negative ion sources.
AB  - Radiofrequency heating for ICP (inductively coupled plasma) ion sources depends
      on the source operating pressure, the presence or absence of a Faraday shield,
      the driver coil geometry, the frequency used, and the magnetic field
      configuration: in negative ion source a magnetic filter seems necessary for H(-)
      survival. The result of single particle simulations showing the possibility of
      electron acceleration in the preglow regime and for reasonable driver chamber
      radius (15 cm) is reported, also as a function of the static external magnetic
      field. An effective plasma conductivity, depending not only from electron
      density, temperature, and rf field but also on static magnetic field is here
      presented and compared to previous models. Use of this conductivity and of
      multiphysics tools for a plasma transport and heating model is shown and
      discussed for a small source.

PMID- 22380303
TI  - Experimental electron energy distribution function investigation at initial stage
      of electron cyclotron resonance discharge.
AB  - Experimental investigation is undertaken to study formation of electron energy
      distribution function (EEDF) at the initial stage of electron cyclotron resonance
      (ECR) discharge inside magnetic mirror trap. In experiment, where discharge was
      initiated by high power radiation of gyrotron operated in the mm-wavelength
      range, electrons were revealed to leave the trap having EEDF be quite different
      from Maxwellian one. Specifically, the EEDF was found to decrease slowly with
      energy up to 400-500 keV and drops abruptly further. The possible physical
      mechanisms are discussed to explain losses of high energy electrons from the trap
      and a limitation of their energy.

PMID- 22380304
TI  - Nonstationary process of ion bunch acceleration in flat diode.
AB  - Nonstationary process of ion bunch acceleration in flat diode was investigated.
      Accurate self-consistent solution for Vlasov equation was obtained. Current
      dependence from longitudinal emittance, ion sound velocity and rate of anode
      potential value growth was found, and current density value is shown to exceed
      Child-Langmuir limit current.

PMID- 22380305
TI  - Isotope fractionation in surface ionization ion source of alkaline-earth iodides.
AB  - The relationship between the isotope fractionation of alkaline-earth elements in
      the surface ionization ion source and the evaporation filament current, i.e.,
      filament temperature, was studied. It was confirmed that the isotope
      fractionation depends on the evaporation filament temperature; the isotope
      fractionation in the case of higher temperature of filament becomes larger. The
      ionization and evaporation process in the surface ionization ion source was
      discussed, and it was concluded that the isotope fractionation is suppressed by
      setting at the lower temperature of evaporation filament because the
      dissociations are inhibited on the evaporation filament.

PMID- 22380306
TI  - Compression and focusing a laser produced plasma using a plasma optical system.
AB  - Axi-symmetric compression and focusing of a low temperature laser produced copper
      plasma with an electrostatic plasma optical system was investigated for the first
      time. The degree of plasma concentration was quantified using Langmuir ion
      measurements of the ion flow and optical measurements of the thickness
      distributions of copper depositions on glass substrates. Both the ion flow and
      the deposition measurements showed strong concentration of the ion-plasma flow
      towards the axis. The ion current density at the focus was compressed by a factor
      up to 9. The on-axis deposition rate was increased by about the same factor.

PMID- 22380307
TI  - Automatic generation of IGUN(C) input files for enhanced mesh resolution at the
      plasma meniscus.
AB  - The plasma-beam interface (meniscus) is highly nonlinear and its correct
      simulation needs a mesh resolution of the order of the Debye length. In high
      intensity ion sources, the plasma density is usually too high and the Debye
      length is too small for a sufficient mesh resolution. A well established method
      to overcome this dilemma is the use of a field line and an equipotential line to
      be created in a first run, in order to dissect the simulation problem into a
      plasma part with much higher mesh resolution and a transport part with usual
      resolution. In the past many users of IGUN have found it difficult to perform
      this dissection. Therefore, a new feature has been added to IGUN to automatically
      write new input files for the dissected areas. For this a field line starting
      point needs to be defined as well as the potential of a pseudo electrode. The
      field line then is used for the plasma part as a slanted and curved Neumann
      boundary, while the pseudo electrode will act as the extraction electrode. The
      trajectory end data then are used in the automatically generated concatenating
      run as ion starting input without any need for the user to adjust for positions
      or different mesh resolutions. Here we show as an example the simulation of the
      well-known CHORDIS ion source, the calculated field line, the pseudo
      equipotential line, and the resulting simulations for the automatically generated
      input files for the plasma and the transport parts.

PMID- 22380308
TI  - Effects of electrode geometry on the ion beam extraction of closed drift type
      anode layer linear ion source.
AB  - Closed drift type anode layer linear ion source was investigated with focusing on
      the electrode geometry effects on ion beam emission and anode layer formation. In
      the electrode geometry, the discharge gap between anode and cathode plays an
      important role to control anode layer formation as well as electron generation.
      When the discharge gap is increased from 2 to 3 mm, the ion current density was
      enhanced from 0.9 to 1.35 mA/cm(2). Computational simulation by using an object
      oriented particle in cell showed that the discharge volume was extended due to
      enhanced electron generation and the electric field at the anode layer was
      enhanced from 1.32 to 1.52 MV/cm.

PMID- 22380309
TI  - Electrostatic energy analyzer measurements of low energy zirconium beam
      parameters in a plasma sputter-type negative ion source.
AB  - A plasma sputter-type negative ion source is utilized to produce and detect
      negative Zr ions with energies between 150 and 450 eV via a retarding potential
      type electrostatic energy analyzer. Traditional and modified semi-cylindrical
      Faraday cups (FC) inside the analyzer are employed to sample negative Zr ions and
      measure corresponding ion currents. The traditional FC registered indistinct ion
      current readings which are attributed to backscattering of ions and secondary
      electron emissions. The modified Faraday cup with biased repeller guard ring, cut
      out these signal distortions leaving only ringings as issues which are
      theoretically compensated by fitting a sigmoidal function into the data. The mean
      energy and energy spread are calculated using the ion current versus retarding
      potential data while the beam width values are determined from the data of the
      transverse measurement of ion current. The most energetic negative Zr ions yield
      tighter energy spread at 4.11 eV compared to the least energetic negative Zr ions
      at 4.79 eV. The smallest calculated beam width is 1.04 cm for the negative Zr
      ions with the highest mean energy indicating a more focused beam in contrast to
      the less energetic negative Zr ions due to space charge forces.

PMID- 22380310
TI  - Low energy beam transport for facility for rare isotope beams driver linear
      particle accelerator.
AB  - The driver linac for the facility for rare isotope beams (FRIB) will provide a
      wide range of primary ion beams for nuclear physics research. The linac will be
      capable of accelerating a uranium beam to an energy of up to 200 Mev/u and
      delivering it to a fragmentation target with a maximum power of 400 kW. Stable
      ion beams will be produced by a high performance electron cyclotron resonance ion
      source operating at 28 GHz. The ion source will be located on a high voltage
      platform to reach an initial beam energy of 12 keV/u. After extraction, the ion
      beam will be transported vertically down to the linac tunnel in a low energy beam
      transport (LEBT) system and injected into a radio frequency quadrupole (RFQ)
      operating at a frequency of 80.5 MHz. To meet the beam power requirements,
      simultaneous acceleration of two-charge states will be used for heavier ions
      (>=Xe). This paper presents the layout of the FRIB LEBT and the beam dynamics in
      the LEBT. In particular, simulation and design of the beam line section before
      charge state selection will be detailed. The need to use an achromatic design for
      the charge state selection system and the advantage of an ion beam collimation
      system to limit the emittance of the beam injected into the RFQ will be discussed
      in this paper.

PMID- 22380311
TI  - Progress towards the development of a realistic electron cyclotron resonance ion
      source extraction model.
AB  - In this paper, an ongoing effort to provide a simulation and design tool for
      electron cyclotron resonance ion source extraction and low energy beam transport
      is described and benchmarked against experimental results. Utilizing the particle
      in-cell code WARP, a set of scripts has been developed: A semiempirical method of
      generating initial conditions, a 2D-3D hybrid method of plasma extraction and a
      simple beam transport deck. Measured emittances and beam profiles of uranium and
      helium beams are shown and the influence of the sextupole part of the plasma
      confinement field is investigated. The results are compared to simulations
      carried out using the methods described above. The results show that the
      simulation model (with some additional refinements) represents highly charged,
      well-confined ions well, but that the model is less applicable for less confined,
      singly charged ions.

PMID- 22380312
TI  - Use of the focusing multi-slit ion optical system at RUssian Diagnostic Injector
      (RUDI).
AB  - The upgrade of the diagnostic neutral beam injector RUDI in 2010 was performed to
      increase the beam density at the focal plane in accordance with the requirements
      of charge-exchange recombination spectroscopy diagnostics. A new focusing ion
      optical system (IOS) with slit beamlets and an enlarged aperture was optimized
      for 50% higher nominal beam current and reduced angular divergence with respect
      to the previous multi-aperture IOS version. The upgraded injector provides the
      beam current up to 3 A, the measured beam divergence in the direction along the
      slits is 0.35 degrees . Additionally, the plasma generator was modified to extend
      the beam pulse to 8 s.

PMID- 22380313
TI  - Development of low-energy and high-current-density ion beam system.
AB  - A low-energy ion beam system operating at a dc voltage of less than 300 V was
      developed using an ion source with a multicusp magnetic field. A high-current
      density ion beam of 6.9 mA/cm(2) was successfully extracted at the electrode. The
      beam extraction characteristics for flat and concave electrodes were compared. In
      the case of a concave electrode with a designed focal length of 350 mm, it was
      observed that the beam profile was sharper than that obtained using a flat
      electrode.

PMID- 22380314
TI  - Study of space charge compensation phenomena in charged particle beams.
AB  - The propagation of a charged particle beam is accompanied by the production of
      secondary particles created in the interaction of the beam itself with the
      background gas flowing in the accelerator tube. In the drift region, where the
      electric field of the electrodes is negligible, secondary particles may
      accumulate giving a plasma which shields the self-induced potential of the
      charged beam. This phenomenon, known as space charge compensation is a typical
      issue in accelerator physics, where it is usually addressed by means of 1D radial
      transport codes or Monte Carlo codes. The present paper describes some
      theoretical studies on this phenomenon, presenting a Particle in Cell-Monte Carlo
      (PIC-MC) Code developed ad hoc where both radial and axial confinements of
      secondary particles are calculated. The features of the model, offering a new
      insight on the problem, are described and some results discussed.

PMID- 22380315
TI  - A new extraction system for the Linac4 H- ion source.
AB  - As part of the CERN accelerator complex upgrade, a new linear accelerator for H(
      ) (Linac4) is under construction. The ion source design is based on the non
      caesiated DESY RF-driven ion source, with the goal of producing an H(-) beam of
      80 mA beam current, 45 keV beam energy, 0.4 ms pulse length, and 2 Hz repetition
      rate. The source has been successfully commissioned for an extraction voltage of
      35 kV, corresponding to the one used at DESY. Increasing the extraction voltage
      to 45 kV has resulted in frequent high voltage breakdowns in the extraction
      region caused by evaporating material from the electron dump, triggering a new
      design of the extraction and electron dumping system. Results of the ion source
      commissioning at 35 kV are presented as well as simulations of a new pulsed
      extraction system for beam extraction at 45 kV.

PMID- 22380316
TI  - Deuteron injector for Peking University Neutron Imaging Facility project.
AB  - The deuteron injector developed for the PKUNIFTY (Peking University Neutron
      Imaging Facility) has been installed and commissioned at Peking University (PKU).
      The injector system must transfer 50 keV 50 mA of D(+) ion beam to the entrance
      of the 2 MeV radio frequency quadrupole (RFQ) with 10% duty factor (1 ms, 100
      Hz). A compact 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) ion
      source and a 1.36 m long low energy beam transport (LEBT) line using two
      solenoids was developed as the deuteron injector. A phi5 mm four-quadrant
      diaphragm was used to simulate the entrance of RFQ electrodes. The beam
      parameters are measured after this core with an emittance measurement unit (EMU)
      and a bending magnet for ion fraction analysis at the end of injector. During the
      commissioning, 77 mA of total deuteron beam was extracted from PMECR and 56 mA of
      pure D(+) beam that passed through the phi5 mm four-quadrant diaphragm was
      obtained at the position of RFQ entrance with the measured normalized rms
      emittance 0.12-0.16pi mm mrad. Ion species analysis results show that the
      deuteron fraction is as high as 99.5%. All of the parameters satisfy PKUNIFTY's
      requirements. In this paper, we will describe the deuteron injector design and
      report the commissioning results as well as the initial operation.

PMID- 22380317
TI  - Use of a wire scanner for monitoring residual gas ionization in Soreq Applied
      Research Accelerator Facility 20 keV/u proton/deuteron low energy beam transport
      beam line.
AB  - The ion source end of the Soreq Applied Research Accelerator Facility accelerator
      consists of a proton/deuteron ECR ion source and a low energy beam transport
      (LEBT) beam line. An observed reduction of the radio frequency quadrupole
      transmission with increase of the LEBT current prompted additional study of the
      LEBT beam properties. Numerous measurements have been made with the LEBT bream
      profiler wire biased by a variable voltage. Current-voltage characteristics in
      presence of the proton beam were measured even when the wire was far out of the
      beam. The current-voltage characteristic in this case strongly resembles an
      asymmetric diodelike characteristic, which is typical of Langmuir probes
      monitoring plasma. The measurement of biased wire currents, outside the beam,
      enables us to estimate the effective charge density in vacuum.

PMID- 22380318
TI  - Study on the beam transport from the Bio-Nano ECRIS.
AB  - The beam transport of N(+) ion and C(60)(+) ion in the Bio-Nano ECRIS with min-B
      configuration was investigated based on the ion beam profiles. The N(+) beam
      could be focused under the low-beam current conditions. Also the C(60)(+) beam
      could be focused in spite of the large space-charge effect which will lead the
      divergence of the beam. We confirmed that our beam transport system works well
      even for the C(60)(+) ion beam. We estimated the highest C(60)(+) beam current
      with the focused beam profile by comparing the N(+) ion beam.

PMID- 22380319
TI  - Effect of beam limiting aperture and collector potential on multi-element focused
      ion beams.
AB  - A compact microwave driven plasma based multi-element focused ion beam system has
      been developed. In the present work, the effect of reduced beam limiter (BL)
      aperture on the focused ion beam parameters, such as current and spot size, and a
      method of controlling beam energy independently by introducing a biased collector
      at focal point (FP) are investigated. It is found that the location of FP does
      not change due to the reduction of BL aperture. The location of FP and beam size
      are found to be weakly dependent on the collector potential in the range from -8
      kV to -18 kV.

PMID- 22380320
TI  - Hollow target magnetron-sputter-type solid material ion source.
AB  - A thin-walled aluminum (Al) hollow electrode has been inserted into an ion source
      to serve as an electrode for a radio frequency magnetron discharge. The produced
      plasma stabilized by argon (Ar) gas sputters the Al electrode to form a beam of
      Al(+) and Ar(+) ions. The total beam current extracted through a 3 mm diameter
      extraction hole has been 50 MUA, with the Al(+) ion beam occupying 30% of the
      total beam current.

PMID- 22380321
TI  - Ion energy distribution functions of low energy beams formed by wire extraction
      electrodes.
AB  - The two-electrode extractor system made of 0.1 mm diameter tungsten wires
      separated by 0.7 mm has formed an argon ion beam with 50 V extraction potential.
      Energy spreads of the extracted beams were typically less than 2 eV when the beam
      current density was low. The beam intensity rapidly decreased as the distance
      between the extractor and the beam detector increased, indicating space charge
      limited transport of the beam. Problems associated with the emittance
      measurements are also discussed.

PMID- 22380322
TI  - Production and acceleration of ion beams by laser ablation.
AB  - In this work, we present a new pulsed laser ablation technique to obtain
      energetic ion beams. The accelerator we made is a compact device able to extract
      and accelerate the ionic components of plasma up to 160 keV per charge state. It
      is composed by a generating chamber containing an expansion chamber used like
      first electrode. Next, a second electrode connected to ground and a third
      electrode connected to negative voltage are used. The third electrode is used
      also as Faraday cup. By the analysis of the ion signals we studied the plume
      parameters such as TOF accelerated signals, charge state, and divergence.

PMID- 22380323
TI  - An alpha particle measurement system using an energetic neutral helium beam in
      ITER (invited).
AB  - An energetic helium neutral beam is involved in the beam neutralization
      measurement system of alpha particles confined in a DT fusion plasma. A full size
      strong-focusing He(+) ion source (2 A, the beam radius of 11.3 mm, the beam
      energy less than 20 keV). Present strong-focusing He(+) ion source shows an
      emittance diagram separated for each beamlet of multiple apertures without phase
      space mixing, despite the space charge of a beamlet is asymmetric and the beam
      flow is non-laminar. The emittance of beamlets in the peripheral region was
      larger than that of center. The heat load to the plasma electrode was studied to
      estimate the duty factor for the ITER application.

PMID- 22380324
TI  - H- beam transport experiments in a solenoid low energy beam transport.
AB  - The Front End Test Stand (FETS) is located at Rutherford Appleton Laboratory and
      aims for a high current, fast chopped 3 MeV H(-) ion beam suitable for future
      high power proton accelerators like ISIS upgrade. The main components of the
      front end are the Penning ion source, a low energy beam transport line, an radio
      frequency quadrupole (RFQ) and a medium energy beam transport (MEBT) providing
      also a chopper section and rebuncher. FETS is in the stage of commissioning its
      low energy beam transport (LEBT) line consisting of three solenoids. The LEBT has
      to transport an H(-) high current beam (up to 60 mA) at 65 keV. This is the
      injection energy of the beam into the RFQ. The main diagnostics are slit-slit
      emittance scanners for each transversal plane. For optimizing the matching to the
      RFQ, experiments have been performed with a variety of solenoid settings to
      better understand the actual beam transport. Occasionally, source parameters such
      as extractor slit width and beam energy were varied as well. The paper also
      discusses simulations based on these measurements.

PMID- 22380325
TI  - Investigations on the structure of the extracted ion beam from an electron
      cyclotron resonance ion source.
AB  - Using improved beam diagnostic tools, the structure of an ion beam extracted from
      an electron cyclotron resonance ion source (ECRIS) becomes visible. Especially
      viewing targets to display the beam profile and pepper pot devices for emittance
      measurements turned out to be very useful. On the contrary, diagnostic tools
      integrating over one space coordinate like wire harps for profile measurements or
      slit-slit devices, respectively slit-grid devices to measure the emittance might
      be applicable for beam transport investigations in a quadrupole channel, but are
      not very meaningful for investigations regarding the given ECRIS symmetry. Here
      we try to reproduce the experimentally found structure on the ion beam by
      simulation. For the simulation, a certain model has to be used to reproduce the
      experimental results. The model is also described in this paper.

PMID- 22380326
TI  - A neutron diagnostic for high current deuterium beams.
AB  - A neutron diagnostic for high current deuterium beams is proposed for
      installation on the spectral shear interferometry for direct electric field
      reconstruction (SPIDER, Source for Production of Ion of Deuterium Extracted from
      RF plasma) test beam facility. The proposed detection system is called Close
      contact Neutron Emission Surface Mapping (CNESM). The diagnostic aims at
      providing the map of the neutron emission on the beam dump surface by placing a
      detector in close contact, right behind the dump. CNESM uses gas electron
      multiplier detectors equipped with a cathode that also serves as neutron-proton
      converter foil. The cathode is made of a thin polythene film and an aluminium
      film; it is designed for detection of neutrons of energy >2.2 MeV with an
      incidence angle < 45 degrees . CNESM was designed on the basis of simulations of
      the different steps from the deuteron beam interaction with the beam dump to the
      neutron detection in the nGEM. Neutron scattering was simulated with the MCNPX
      code. CNESM on SPIDER is a first step towards the application of this diagnostic
      technique to the MITICA beam test facility, where it will be used to resolve the
      horizontal profile of the beam intensity.

PMID- 22380327
TI  - Dynamical changes of ion current distribution for a Penning discharge source
      using a Langmuir probe array.
AB  - A paralleled plate electrode and a 9-tip Langmuir probe array located 1 mm behind
      the extraction exit of a cold cathode Penning ion source are employed to measure
      the total current and the dynamical changes of the ion current in the 2D profile,
      respectively. Operation of the ion source by 500 V DC power supply, the
      paralleled plate electrode and the Langmuir probe array are driven by a bias
      voltage ranging from -200 V to 200 V. The dependence of the total current and the
      dynamical changes of the ion current in the 2D profile are presented at the
      different bias voltage. The experimental results show that the distribution of
      ion current is axial symmetry and approximate a unimodal distribution.

PMID- 22380328
TI  - Electrostatic plasma lens for focusing negatively charged particle beams.
AB  - We describe the current status of ongoing research and development of the
      electrostatic plasma lens for focusing and manipulating intense negatively
      charged particle beams, electrons, and negative ions. The physical principle of
      this kind of plasma lens is based on magnetic isolation electrons providing
      creation of a dynamical positive space charge cloud in shortly restricted volume
      propagating beam. Here, the new results of experimental investigations and
      computer simulations of wide-aperture, intense electron beam focusing by plasma
      lens with positive space charge cloud produced due to the cylindrical anode layer
      accelerator creating a positive ion stream towards an axis system is presented.

PMID- 22380329
TI  - Design and specifications of the diagnostics for the instrumented calorimeter of
      source for the production of ions of deuterium extracted from radio frequency
      plasma.
AB  - In the development of the neutral beam injector for ITER experiment, the test
      facility SPIDER is going to be built. To measure the beam parameters, several
      diagnostics are used. One of them is the Short-Time Retractable Instrumented
      Kalorimeter Experiment (STRIKE) which measures beam uniformity, beamlet
      divergence, and stripping losses. This contribution gives an overview of the
      diagnostics dedicated to these measurements: thermal cameras, thermocouples,
      current sensors, and electrostatic sensors. The specifications of these
      diagnostics have been defined according to the results of electrostatic and
      thermal simulations. A failure modes and effects analysis has been performed
      during the design. Consequently the project of the STRIKE diagnostics has been
      optimized to reduce the possible failure risks.

PMID- 22380330
TI  - Thermal and electrostatic simulations of the diagnostic calorimeter for the
      source for production of ion of deuterium extracted from RF plasma beam.
AB  - To study and optimise negative ion production for the ITER neutral beam
      injectors, a test facility is under construction in Padova with the aim of
      testing beam characteristics and to verify the source proper operation. The
      instrumented calorimeter STRIKE (short-time retractable instrumented kalorimeter
      experiment) is being developed to characterise the SPIDER (Source for Production
      of Ion of Deuterium Extracted from RF plasma) beam during short operations. The
      paper presents an investigation of the response of STRIKE measurement systems. It
      results that biasing is necessary to cope with the influence of secondary
      electrons on current measurements; moreover, despite the discretisation of the
      recorded thermal patterns introduced by the pixels of thermal cameras, a
      sufficient spatial resolution is expected.

PMID- 22380331
TI  - Study of ion beam transport from the SECRAL electron cyclotron resonance ion
      source at the Institute of Modern Physics.
AB  - Ion beam transport from the Superconducting Electron Cyclotron Resonance ion
      source with Advanced design in Lanzhou (SECRAL) electron cyclotron resonance ion
      source was studied at the Institute of Modern Physics during 2010. Particle-in
      cell simulations and experimental results have shown that both space charge and
      magnetic aberrations lead to a larger beam envelope and emittance growth. In the
      existing SECRAL extraction beam line, it has been shown that raising the solenoid
      lens magnetic field reduces aberrations in the subsequent dipole and results in
      lower emittance. Detailed beam emittance measurements are presented in this
      paper.

PMID- 22380332
TI  - Low-energy beam transport studies supporting the spallation neutron source 1-MW
      beam operation.
AB  - The H(-) injector consisting of a cesium enhanced RF-driven ion source and a 2
      lens electrostatic low-energy beam transport (LEBT) system supports the
      spallation neutron source 1 MW beam operation with ~38 mA beam current in the
      linac at 60 Hz with a pulse length of up to ~1.0 ms. In this work, two important
      issues associated with the low-energy beam transport are discussed: (1)
      inconsistent dependence of the post-radio frequency quadrupole accelerator beam
      current on the ion source tilt angle and (2) high power beam losses on the LEBT
      electrodes under some off-nominal conditions compromising their reliability.

PMID- 22380333
TI  - Laser and focused ion beam combined machining for micro dies.
AB  - We have developed a laser and focused ion beam (FIB) compound process for press
      mold dies of a micro lens array (MLA) and a micro needle array (MNA) in a glassy
      carbon (GC). The press mold die of the MLA was roughly fabricated by UV-YAG
      laser. After this process, we finished this surface by scanning FIB. As a result,
      higher accuracy and good roughness of surface profile can be realized. An optical
      glass is used to confirm the shape of lens. Moreover, we fabricated 6 * 6 through
      holes in the GC by the spiral drilling in addition to the focus position movement
      of the UV laser for press mold die of the MNA. After the FIB process, we were
      able to make the needle die of surface and hole wall roughness less than 0.9 MUm.
      A silicon rubber is used to confirm the shape of the holes.

PMID- 22380334
TI  - The second generation Singapore high resolution proton beam writing facility.
AB  - A new proton beam focusing facility, designed for proton beam writing (PBW)
      applications has been tested. PBW allows for proximity free structuring of high
      aspect ratio, high-density 3D nanostructures. The new facility is designed around
      OM52 compact quadrupole lenses capable of operating in a variety of high
      demagnification configurations. Performance tests show that proton beams can be
      focused down to 19.0 * 29.9 nm(2) and single line scans show a beam width of 12.6
      nm. The ultimate goal of sub 10 nm structuring with MeV protons will be
      discussed.

PMID- 22380335
TI  - A TandetronTM as proton injector for the eye tumor therapy in Berlin.
AB  - The therapy of eye tumors with fast protons is an excellent tool giving very high
      local control rates. At the Helmholtz-Zentrum Berlin (HZB) almost 1800 patients
      were treated since 1998. A 2 MV TandetronTM was installed as injector for the k =
      132 HZB cyclotron. Using the standard 358 duoplasmatron ion source with direct
      extraction of negative hydrogen ions an extremely stable proton beam can be
      delivered, both on the short-term and the long-term scale. The hair-needle
      filaments made from thoriated tungsten wires have safe operation times of more
      than 1000 h.

PMID- 22380336
TI  - Test bench to commission a third ion source beam line and a newly designed
      extraction system.
AB  - The HIT (Heidelberg Ion Beam Therapy Center) is the first hospital-based
      treatment facility in Europe where patients can be irradiated with protons and
      carbon ions. Since the commissioning starting in 2006 two 14.5 GHz electron
      cyclotron resonance ion sources are routinely used to produce a variety of ion
      beams from protons up to oxygen. In the future a helium beam for regular patient
      treatment is requested, therefore a third ion source (Supernanogan source from
      PANTECHNIK S.A.) will be integrated. This third ECR source with a newly designed
      extraction system and a spectrometer line is installed at a test bench at HIT to
      commission and validate this section. Measurements with different extraction
      system setups will be presented to show the improvement of beam quality for
      helium, proton, and carbon beams. An outlook to the possible integration scheme
      of the new ion source into the production facility will be discussed.

PMID- 22380337
TI  - Intense beams from gases generated by a permanent magnet ECR ion source at PKU.
AB  - An electron cyclotron resonance (ECR) ion source is designed for the production
      of high-current ion beams of various gaseous elements. At the Peking University
      (PKU), the primary study is focused on developing suitable permanent magnet ECR
      ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ)
      accelerator and for Peking University Neutron Imaging Facility. Recently, other
      kinds of high-intensity ion beams are required for new acceleration structure
      demonstration, simulation of fusion reactor material irradiation, aviation
      bearing modification, and other applications. So we expanded the ion beam
      category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about
      120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and
      65 mA of He(+) extracted at 50 kV through a phi 6 mm aperture were produced by
      the PMECRs at PKU. Their rms emittances are less than 0.2 pi mm mrad. Tungsten
      samples were irradiated by H(+) or He(+) beam extracted from this ion source and
      H/He holes and bubbles have been observed on the samples. A method to produce a
      high intensity H/He mixed beam to study synergistic effect is developed for
      nuclear material irradiation. To design a He(+) beam injector for coupled radio
      frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were
      carried out on PKU low energy beam transport test bench and the transmission was
      less than 50%. It indicated that some electrode modifications must be done to
      decrease the divergence of He(+) beam.

PMID- 22380338
TI  - Nanostructure operations by means of the liquid metal ion sources.
AB  - Characteristics of a disperse phase of liquid metal ion source on the basis of
      various working substances are investigated. It is revealed that generation of
      the charged particles occurs in the threshold image and is simultaneously
      accompanied by excitation of capillary instability on a surface of the emitter.
      The majority of particles has the size about 2 nm (Sn) and a specific charge of 5
      * 10(4) C/kg. If the working liquid possesses high viscosity (Ni), generation of
      nanodroplets does not occur. Gold nanoparticles are used for deposition on a
      surface of quartz cantilevers with the purpose of increase in sensitivity of
      biosensors and on an external surface of carbon nanotubes for creation pressure
      sensors. By means of an ion source nanostructures can be etched on a flat surface
      of conductive materials without difficult ion optics.

PMID- 22380339
TI  - Numerical simulation of gridded electrostatic lens.
AB  - Gridded electrostatic lenses are frequently used in extraction systems and low
      energy ion beam transport line. Typically, for numerical simulation the grid is
      treated as a metal plate transparent for beam particles. The influence of real
      grid geometry on the beam dynamics in the gridded lens has been investigated by
      KOBRA-3d code. Beam emittance growth for different lens parameters has been
      investigated. Approximating expressions for obtained results are presented. The
      grid geometry providing minimal beam distortions is proposed.

PMID- 22380340
TI  - High-energy metal ion implantation for reduction of surface resistivity of
      alumina ceramic.
AB  - In this work, the possibility to increase the surface conductivity of ceramic
      insulators through their treatment with accelerated metal ion beams produced by a
      MevvaV.Ru vacuum arc source is demonstrated. The increase in surface conductivity
      is made possible due to experimental conditions in which an insulated collector
      is charged by beam ions to a potential many times lower than the accelerating
      voltage, and hence, than the average beam ion energy. The observed effect of
      charge neutralization of the accelerated ion beam is presumably associated with
      electrons knocked out of the electrodes of the accelerating system of the source
      and of the walls of the vacuum chamber by the accelerated ions.

PMID- 22380341
TI  - A review of ion sources for medical accelerators (invited).
AB  - There are two major medical applications of ion accelerators. One is a production
      of short-lived isotopes for radionuclide imaging with positron emission
      tomography and single photon emission computer tomography. Generally, a
      combination of a source for negative ions (usually H- and/or D-) and a cyclotron
      is used; this system is well established and distributed over the world. Other
      important medical application is charged-particle radiotherapy, where the
      accelerated ion beam itself is being used for patient treatment. Two distinctly
      different methods are being applied: either with protons or with heavy-ions
      (mostly carbon ions). Proton radiotherapy for deep-seated tumors has become
      widespread since the 1990s. The energy and intensity are typically over 200 MeV
      and several 10(10) pps, respectively. Cyclotrons as well as synchrotrons are
      utilized. The ion source for the cyclotron is generally similar to the type for
      production of radioisotopes. For a synchrotron, one applies a positive ion source
      in combination with an injector linac. Carbon ion radiotherapy awakens a
      worldwide interest. About 6000 cancer patients have already been treated with
      carbon beams from the Heavy Ion Medical Accelerator in Chiba at the National
      Institute of Radiological Sciences in Japan. These clinical results have clearly
      verified the advantages of carbon ions. Heidelberg Ion Therapy Center and Gunma
      University Heavy Ion Medical Center have been successfully launched. Several new
      facilities are under commissioning or construction. The beam energy is adjusted
      to the depth of tumors. It is usually between 140 and 430 MeV/u. Although the
      beam intensity depends on the irradiation method, it is typically several 10(8)
      or 10(9) pps. Synchrotrons are only utilized for carbon ion radiotherapy. An ECR
      ion source supplies multi-charged carbon ions for this requirement. Some other
      medical applications with ion beams attract developer's interests. For example,
      the several types of accelerators are under development for the boron neutron
      capture therapy. This treatment is conventionally demonstrated by a nuclear
      reactor, but it is strongly expected to replace the reactor by the accelerator.
      We report status of ion source for medical application and such scope for further
      developments.

PMID- 22380342
TI  - High frequency operation of a hot filament cathode for a magnetized plasma ion
      source.
AB  - A tungsten filament cathode has been operated with an ac heating current to
      excite a plasma in a linear magnetic field. Both the discharge current and the
      ion saturation current in plasma near the extraction hole of the ion source
      exhibited fluctuations. The discharge current fluctuated with the amplitude less
      than 2% of the average, and the frequency two times the frequency of the heating
      current. Fluctuation amplitude of the ion saturation current was about 10% of the
      average, while the frequency was the same as that of the heating current. The ac
      operation has prolonged the lifetime of a hot filament cathode by about 50%.

PMID- 22380343
TI  - Study of laser plasma emission from doped targets.
AB  - In this work, the characteristics of laser plasma produced by ablation of pure
      and doped targets are studied. An excimer KrF laser was used to induce ablation.
      Pure Cu, Cu with 2% of Be, and Cu with 4% of Sn targets were ablated to evaluate
      the influence of these admixture on the emission of Cu ions. It was observed that
      the emission of ions exhibited a higher gain from the Cu/Be and Cu/Sn targets
      with respect to the pure Cu one. We also performed studied of ion velocity and
      charge angular distribution.

PMID- 22380344
TI  - Technical use of compact micro-onde devices.
AB  - Due to the very small size of a COMIC (Compact MIcrowave and Coaxial) device [P.
      Sortais, T. Lamy, J. Medard, J. Angot, L. Latrasse, and T. Thuillier, Rev. Sci.
      Instrum. 81, 02B31 (2010)] it is possible to install such plasma or ion source
      inside very different technical environments. New applications of such a device
      are presented, mainly for industrial applications. We have now designed ion
      sources for highly focused ion beam devices, ion beam machining ion guns, or thin
      film deposition machines. We will mainly present new capabilities opened by the
      use of a multi-beam system for thin film deposition based on sputtering by medium
      energy ion beams. With the new concept of multi-beam sputtering (MBS), it is
      possible to open new possibilities concerning the ion beam sputtering (IBS)
      technology, especially for large size deposition of high uniformity thin films.
      By the use of multi-spots of evaporation, each one corresponding to an
      independent tuning of an individual COMIC ion source, it will be very easy to co
      evaporate different components.

PMID- 22380345
TI  - Rhenium ion beam for implantation into semiconductors.
AB  - At the ion source test bench in Institute for Theoretical and Experimental
      Physics the program of ion source development for semiconductor industry is in
      progress. In framework of the program the Metal Vapor Vacuum Arc ion source for
      germanium and rhenium ion beam generation was developed and investigated. It was
      shown that at special conditions of ion beam implantation it is possible to
      fabricate not only homogenous layers of rhenium silicides solid solutions but
      also clusters of this compound with properties of quantum dots. At the present
      moment the compound is very interesting for semiconductor industry, especially
      for nanoelectronics and nanophotonics, but there is no very developed technology
      for production of nanostructures (for example quantum sized structures) with
      required parameters. The results of materials synthesis and exploration are
      presented.

PMID- 22380346
TI  - Compact microwave ion source for industrial applications.
AB  - A 2.45 GHz microwave ion source for ion implanters has many good properties for
      industrial application, such as easy maintenance and long lifetime, and it should
      be compact for budget and space. But, it has a dc current supply for the solenoid
      and a rf generator for plasma generation. Usually, they are located on high
      voltage platform because they are electrically connected with beam extraction
      power supply. Using permanent magnet solenoid and multi-layer dc break, high
      voltage deck and high voltage isolation transformer can be eliminated, and the
      dose rate on targets can be controlled by pulse duty control with semiconductor
      high voltage switch. Because the beam optics does not change, beam transfer
      components, such as focusing elements and beam shutter, can be eliminated. It has
      shown the good performances in budget and space for industrial applications of
      ion beams.

PMID- 22380347
TI  - Point/Counterpoint: The 2014 initiative can have potentially unintended negative
      consequences for medical physics in diagnostic imaging and nuclear medicine.

PMID- 22380348
TI  - Utility of treatment planning for thermochemotherapy treatment of nonmuscle
      invasive bladder carcinoma.
AB  - PURPOSE: A recently completed Phase I clinical trial combined concurrent
      Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse
      applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of
      nonmuscle invasive bladder cancer. This work presents a new treatment planning
      approach, and demonstrates potential impact of this approach on improvement of
      treatment quality. METHODS: This study retrospectively analyzes a subset of five
      patients on the trial. For each treatment, expert operators selected "clinical
      optimal" settings based on simple model calculation on the BSD-2000 control
      console. Computed tomography (CT) scans acquired prior to treatment were
      segmented to create finite element patient models for retrospective simulations
      with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since
      Sigma-HyperPlan does not account for the convective nature of heat transfer
      within a fluid filled bladder, an effective thermal conductivity for bladder was
      introduced. This effective thermal conductivity value was determined by comparing
      simulation results with clinical measurements of bladder and rectum temperatures.
      Regions of predicted high temperature in normal tissues were compared with
      patient complaints during treatment. Treatment results using "computed-optimal"
      settings from the planning system were compared with clinical results using
      clinical-optimal settings to evaluate potential of treatment improvement by
      reducing hot spot volume. RESULTS: For all five patients, retrospective treatment
      planning indicated improved matches between simulated and measured bladder
      temperatures with increasing effective thermal conductivity. The differences were
      mostly within 1.3  degrees C when using an effective thermal conductivity value
      above 10 W/K/m. Changes in effective bladder thermal conductivity affected
      surrounding normal tissues within a distance of ~1.5 cm from the bladder wall.
      Rectal temperature differences between simulation and measurement were large due
      to sensitivity to the sampling locations in rectum. The predicted bladder T90
      correlated well with single-point bladder temperature measurement. Hot spot
      locations predicted by the simulation agreed qualitatively with patient
      complaints during treatment. Furthermore, comparison between the temperature
      distributions with clinical and computed-optimal settings demonstrated that the
      computed-optimal settings resulted in substantially reduced hot spot volumes.
      CONCLUSIONS: Determination of an effective thermal conductivity value for fluid
      filled bladder was essential for matching simulation and treatment temperatures.
      Prospectively planning patients using the effective thermal conductivity
      determined in this work can potentially improve treatment efficacy (compared to
      manual operator adjustments) by potentially lower discomfort from reduced hot
      spots in normal tissue.

PMID- 22380349
TI  - Objective ultrasound elastography scoring of thyroid nodules using spatiotemporal
      strain information.
AB  - PURPOSE: Ultrasound (US) elastography measures the deformation of tissue in
      response to stress to derive and display its stiffness. Typically, the clinicians
      visually inspect and categorize the pseudo-color pattern of an elastography image
      into one of 5-6 different scores. This scoring method could lead to sizable
      variability due to its subjective nature. In this paper, we introduce a new
      method to objectively derive an elasticity score for differential diagnosis of
      thyroid nodules using US elastography. METHODS: Elastography data from 106
      patients (123 nodules: 103 benign and 20 malignant) referred for a fine needle
      aspiration (FNA) biopsy were used for this retrospective study. No external
      compression was applied since carotid artery pulsation was used as the
      compression source. Elasticity contrast index (ECI), which was derived using
      spatiotemporal strain information, was computed to quantify the local stiffness
      contrast within a nodule. A larger ECI value suggests a stiffer nodule, thus
      indicating an increased likelihood of being malignant. RESULTS: The mean ECI
      value of malignant nodules (0.83 +/- 0.23) was significantly higher than that of
      benign nodules (0.53 +/- 0.18) (p = 0.00002). Using a cut-off value of 0.60, 19
      malignant nodules and 76 benign nodules were detected correctly, leading to the
      sensitivity, specificity, positive predictive value and negative predictive value
      of 95%, 73.8%, 41.3%, and 98.7%, respectively. CONCLUSIONS: The objective
      determination of an elasticity score by our method could reduce variability in
      scoring, leading to more reliable elastography results. With further clinical
      validation, we believe that ultrasound elastography could be used as an FNA
      triage tool in managing thyroid nodules.

PMID- 22380350
TI  - Ray-based approach to skeletal muscle perfusion measurement on interventional x
      ray systems.
AB  - PURPOSE: Periprocedural assessment of tissue perfusion by imaging methods could
      improve outcome control during treatment of peripheral vascular disease.
      Currently, endovascular revascularization treatments are assessed by planar
      angiography which only allows for qualitative inspection of blood flow in
      vessels. In this paper, we present a method for periprocedural perfusion
      estimation based on temporal attenuation curves in skeletal muscles using
      angiographic C-arm systems. METHODS: The proposed method tackles the loss of
      spatial depth information which occurs in conventional angiography by combining
      the acquired angiograms with two additional C-arm rotational soft tissue scans.
      The area subject to contrast propagation is segmented from the two images that
      are tomographically reconstructed from the rotational scans and is then used to
      estimate the spatially averaged temporal contrast attenuation along the x-ray
      directions from the angiograms. A segmentation method which is tailored to the
      estimation procedure is applied to limit inaccuracies in the estimation. The
      accuracy of the method in estimating tissue blood flow in muscular tissue is
      evaluated in a simulation study using experimental data from CT perfusion
      acquisitions. RESULTS: Results show that perfusion estimation accuracy is limited
      owing to spatial inhomogeneity of contrast in muscular tissue and to the presence
      of vessels along the x-ray directions. Nonetheless, the spatially averaged
      perfusion quantification allows for improved visual differentiation of normal and
      hypoperfused tissue in comparison with conventional digital subtraction
      angiography. CONCLUSIONS: Periprocedural assessment of muscle perfusion through
      digital subtraction angiography is challenging due to lack of longitudinal
      information in the planar projections. By including additional 3D information on
      the anatomy retrieved from rotational soft tissue scans, the visualization and
      differentiation of normal and hypoperfused areas can be improved.

PMID- 22380351
TI  - Fast compressed sensing-based CBCT reconstruction using  Barzilai-Borwein
      formulation for application to on-line IGRT.
AB  - PURPOSE: Compressed sensing theory has enabled an accurate, low-dose cone-beam
      computed tomography (CBCT) reconstruction using a minimal number of noisy
      projections. However, the reconstruction time remains a significant challenge for
      practical implementation in the clinic. In this work, we propose a novel gradient
      projection algorithm, based on the Gradient-Projection-Barzilai-Borwein
      formulation (GP-BB), that handles the total variation (TV)-norm regularization
      based least squares problem for the CBCT reconstruction in a highly efficient
      manner, with speed acceptable for routine use in the clinic. METHODS: CBCT is
      reconstructed by minimizing an energy function consisting of a data fidelity term
      and a TV-norm regularization term. Both terms are simultaneously minimized by
      calculating the gradient projection of the energy function with the step size
      determined using an approximate Hessian calculation at each iteration, based on
      the Barzilai-Borwein formulation. To speed up the process, a multiresolution
      optimization is used. In addition, the entire algorithm was designed to run with
      a single graphics processing unit (GPU) card. To evaluate the performance, the
      Shepp-Logan numerical phantom, the CatPhan 600 physical phantom, and a clinically
      treated head-and-neck patient were acquired from the TrueBeamTM system (Varian
      Medical Systems, Palo Alto, CA). For each scan, in total, 364 projections were
      acquired in a 200 degrees  rotation. The imager has 1024 * 768 pixels with 0.388
      * 0.388-mm resolution. This was down-sampled to 512 * 384 pixels with 0.776 *
      0.776-mm resolution for reconstruction. Evenly spaced angles were subsampled and
      used for varying the number of projections for the image reconstruction. To
      assess the performance of our GP-BB algorithm, we have implemented and compared
      with three compressed sensing-type algorithms, the two of which are popular and
      published (forward-backward splitting techniques), and the other one with a basic
      line-search technique. In addition, the conventional Feldkamp-Davis-Kress (FDK)
      reconstruction of the clinical patient data is compared as well. RESULTS: In
      comparison with the other compressed sensing-type algorithms, our algorithm
      showed convergence in <=30 iterations whereas other published algorithms need at
      least 50 iterations in order to reconstruct the Shepp-Logan phantom image. With
      the CatPhan phantom, the GP-BB algorithm achieved a clinically-reasonable image
      with 40 projections in 12 iterations, in less than 12.6 s. This is at least an
      order of magnitude faster in reconstruction time compared with the most recent
      reports utilizing GPU technology given the same input projections. For the head
      and-neck clinical scan, clinically-reasonable images were obtained from 120
      projections in 34-78 s converging in 12-30 iterations. In this reconstruction
      range (i.e., 120 projections) the image quality is visually similar to or better
      than the conventional FDK reconstructed images using 364 projections. This
      represents a dose reduction of nearly 67% (120/364 projections) while maintaining
      a reasonable speed in clinical implementation. CONCLUSIONS: In this paper, we
      proposed a novel, fast, low-dose CBCT reconstruction algorithm using the Barzilai
      Borwein step-size calculation. A clinically viable head-and-neck image can be
      obtained within ~34-78 s while simultaneously cutting the dose by approximately
      67%. This makes our GP-BB algorithm potentially useful in an on-line image-guided
      radiation therapy (IGRT).

PMID- 22380352
TI  - Kilovoltage energy imaging with a radiotherapy linac with a continuously variable
      energy range.
AB  - PURPOSE: In this paper, the effect on image quality of significantly reducing the
      primary electron energy of a radiotherapy accelerator is investigated using a
      novel waveguide test piece. The waveguide contains a novel variable coupling
      device (rotovane), allowing for a wide continuously variable energy range of
      between 1.4 and 9 MeV suitable for both imaging and therapy. METHOD: Imaging at
      linac accelerating potentials close to 1 MV was investigated experimentally and
      via Monte Carlo simulations. An imaging beam line was designed, and planar and
      cone beam computed tomography images were obtained to enable qualitative and
      quantitative comparisons with kilovoltage and megavoltage imaging systems. The
      imaging beam had an electron energy of 1.4 MeV, which was incident on a water
      cooled electron window consisting of stainless steel, a 5 mm carbon electron
      absorber and 2.5 mm aluminium filtration. Images were acquired with an amorphous
      silicon detector sensitive to diagnostic x-ray energies. RESULTS: The x-ray beam
      had an average energy of 220 keV and half value layer of 5.9 mm of copper. Cone
      beam CT images with the same contrast to noise ratio as a gantry mounted
      kilovoltage imaging system were obtained with doses as low as 2 cGy. This dose is
      equivalent to a single 6 MV portal image. While 12 times higher than a 100 kVp
      CBCT system (Elekta XVI), this dose is 140 times lower than a 6 MV cone beam
      imaging system and 6 times lower than previously published LowZ imaging beams
      operating at higher (4-5 MeV) energies. CONCLUSIONS: The novel coupling device
      provides for a wide range of electron energies that are suitable for kilovoltage
      quality imaging and therapy. The imaging system provides high contrast images
      from the therapy portal at low dose, approaching that of gantry mounted
      kilovoltage x-ray systems. Additionally, the system provides low dose imaging
      directly from the therapy portal, potentially allowing for target tracking during
      radiotherapy treatment. There is the scope with such a tuneable system for
      further energy reduction and subsequent improvement in image quality.

PMID- 22380353
TI  - Development of brain PET using GAPD arrays.
AB  - PURPOSE: In recent times, there has been great interest in the use of Geiger-mode
      avalanche photodiodes (GAPDs) as scintillator readout in positron emission
      tomography (PET) detectors because of their advantages, such as high gain,
      compact size, low power consumption, and magnetic field insensitivity. The
      purpose of this study was to develop a novel PET system based on GAPD arrays for
      brain imaging. METHODS: The PET consisted of 72 detector modules arranged in a
      ring of 330 mm diameter. Each PET module was composed of a 4 * 4 matrix of 3 * 3
      * 20 mm(3) cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled
      with a 4 * 4 array three-side tileable GAPD. The signals from each PET module
      were fed into preamplifiers using a 3 m long flat cable and then sent to a
      position decoder circuit (PDC), which output a digital address and an analog
      pulse of the interacted channel among 64 preamplifier signals transmitted from
      four PET detector modules. The PDC outputs were fed into field programmable gate
      array (FPGA)-embedded data acquisition (DAQ) boards. The analog signal was then
      digitized, and arrival time and energy of the signal were calculated and stored.
      RESULTS: The energy and coincidence timing resolutions measured for 511 keV gamma
      rays were 18.4 +/- 3.1% and 2.6 ns, respectively. The transaxial spatial
      resolution and sensitivity in the center of field of view (FOV) were 3.1 mm and
      0.32% cps/Bq, respectively. The rods down to a diameter of 2.5 mm were resolved
      in a hot-rod phantom image, and activity distribution patterns between the white
      and gray matters in the Hoffman brain phantom were well imaged. CONCLUSIONS:
      Experimental results indicate that a PET system can be developed using GAPD
      arrays and the GAPD-based PET system can provide high-quality PET imaging.

PMID- 22380354
TI  - Scatter factors assessment in microbeam radiation therapy.
AB  - PURPOSE: The success of the preclinical studies in Microbeam Radiation Therapy
      (MRT) paved the way to the clinical trials under preparation at the Biomedical
      Beamline of the European Synchrotron Radiation Facility. Within this framework,
      an accurate determination of the deposited dose is crucial. With that aim, the
      scatter factors, which translate the absolute dose measured in reference
      conditions (2 * 2 cm(2) field size at 2 cm-depth in water) to peak doses, were
      assessed. METHODS: Monte Carlo (MC) simulations were performed with two different
      widely used codes, PENELOPE and GEANT4, for the sake of safety. The scatter
      factors were obtained as the ratio of the doses that are deposited by a microbeam
      and by a field of reference size, at the reference depth. The calculated values
      were compared with the experimental data obtained by radiochromic (ISP HD-810)
      films and a PTW 34070 large area chamber. RESULTS: The scatter factors for
      different microbeam field sizes assessed by the two MC codes were in agreement
      and reproduced the experimental data within uncertainty bars. Those correction
      factors were shown to be non-negligible for the future MRT clinical settings: an
      average 30% lower dose was deposited by a 50 MUm microbeam with respect to the
      reference conditions. CONCLUSIONS: For the first time, the scatter factors in MRT
      were systematically studied. They constitute an essential key to deposit accurate
      doses in the forthcoming clinical trials in MRT. The good agreement between the
      different calculations and the experimental data confirms the reliability of this
      challenging micrometric dose estimation.

PMID- 22380355
TI  - Verification of proton range, position, and intensity in IMPT with a 3D liquid
      scintillator detector system.
AB  - PURPOSE: Intensity-modulated proton therapy (IMPT) using spot scanned proton
      beams relies on the delivery of a large number of beamlets to shape the dose
      distribution in a highly conformal manner. The authors have developed a 3D system
      based on liquid scintillator to measure the spatial location, intensity, and
      depth of penetration (energy) of the proton beamlets in near real-time. METHODS:
      The detector system consists of a 20 * 20 * 20 cc liquid scintillator (LS)
      material in a light tight enclosure connected to a CCD camera. This camera has a
      field of view of 25.7 by 19.3 cm and a pixel size of 0.4 mm. While the LS is
      irradiated, the camera continuously acquires images of the light distribution
      produced inside the LS. Irradiations were made with proton pencil beams produced
      with a spot-scanning nozzle. Pencil beams with nominal ranges in water between
      9.5 and 17.6 cm were scanned to irradiate an area of 10 * 10 cm square on the
      surface of the LS phantom. Image frames were acquired at 50 ms per frame.
      RESULTS: The signal to noise ratio of a typical Bragg peak was about 170. Proton
      range measured from the light distribution produced in the LS was accurate to
      within 0.3 mm on average. The largest deviation seen between the nominal and
      measured range was 0.6 mm. Lateral position of the measured pencil beam was
      accurate to within 0.4 mm on average. The largest deviation seen between the
      nominal and measured lateral position was 0.8 mm; however, the accuracy of this
      measurement could be improved by correcting light scattering artifacts. Intensity
      of single proton spots were measured with precision ranging from 3 % for the
      smallest spot intensity (0.005 MU) to 0.5 % for the largest spot (0.04 MU).
      CONCLUSIONS: Our LS detector system has been shown to be capable of fast,
      submillimeter spatial localization of proton spots delivered in a 3D volume. This
      system could be used for beam range, intensity and position verification in IMPT.

PMID- 22380356
TI  - Accelerating phase contrast MR angiography by simplified skipped phase encoding
      and edge deghosting with array coil enhancement.
AB  - PURPOSE: The aim of this work is to investigate the feasibility of accelerating
      phase contrast magnetic resonance angiography (PC-MRA) by the fast imaging method
      of simplified skipped phase encoding and edge deghosting with array coil
      enhancement (S-SPEED-ACE). METHODS: The parallel imaging method of skipped phase
      encoding and edge deghosting with array coil enhancement (SPEED-ACE) is
      simplified for imaging sparse objects like phase contrast MRA. This approach is
      termed S-SPEED-ACE in which k-space is sparsely sampled with skipped phase
      encoding at every Nth step using multiple receiver coils simultaneously. The
      sampled data are then Fourier transformed into a set of ghosted images, each with
      N-fold aliasing ghosts. Given signal sparseness of MRA, the ghosted images are
      modeled with a single-layer structure, in which the most dominant ghost within
      the potentially overlapped ghosts at each pixel is selected to represent the
      signal of that pixel. The single-layer model is analogous to that used in maximum
      intensity-projection (MIP) that selects only the brightest signal even when there
      are overlapped vessels. With an algorithm based on a least-square-error solution,
      a deghosted image is obtained, along with a residual map for quality control. In
      this way, S-SPEED-ACE partially samples k-space using multiple receiver coils in
      parallel, and yields a deghosted image with an acceleration factor of N. Without
      full central k-space sampling and differential filtering, S-SPEED-ACE achieves
      further scan time reduction with a more straightforward reconstruction. In this
      work, S-SPEED-ACE is demonstrated to accelerate a computer simulated PC-MRA and a
      real human 3D PC-MRA, which was acquired using a clinical 1.5 T scanner on a
      healthy volunteer. RESULTS: Images are reconstructed by S-SPEED-ACE to achieve an
      undersampling factor of up to 8.3 with four receiver coils. The reconstructed
      images generally have comparable quality as that of the reference images
      reconstructed from full k-space data. Maximum-intensity-projection images
      generated from the reconstructed images also demonstrated to be consistent as
      those from the reference images. CONCLUSIONS: By taking advantage of signal
      sparsity naturally existing in the data, SPEED-ACE was simplified and its
      efficiency was improved. The feasibility of the proposed S-SPEED-ACE is
      demonstrated in this work with simulated sampling of an actual 3D head PC-MRA
      scan.

PMID- 22380357
TI  - Registration-weighted motion correction for PET.
AB  - PURPOSE: Patient motion during a positron emission tomography (PET) scan can lead
      to significant resolution loss. Two of the main motion correction techniques
      employed to ameliorate the loss of image quality due to respiratory motion in the
      torso are postreconstruction registration (PRR) and motion-compensated image
      reconstruction (MCIR). In this study, the authors investigated whether versions
      of these methods that utilize registration-based weighting of the constituent
      respiratory gated data offer any advantage over the standard versions that use
      equal weighting. The registration-based weights were designed to penalize gates
      that were poorly registered to the reference gate. METHODS: SimSET was used to
      simulate data from the NCAT phantom with six lesions added in the lung and liver.
      Images were reconstructed using registration-weighted PRR and MCIR algorithms,
      where the registration weighting was based on the mutual information (MI) of each
      registered gate and the reference gate. More specifically, relative to equal
      weighting, for which the weight for each gate is the inverse of the number of
      gates, the weights were increased for MI greater than the average MI and reduced
      for gates with MI less than the average MI. A scale factor was used to increase
      the range of the weights, and PRR and MCIR images were produced for a range of
      scale factor values. RESULTS: At the optimal values of the scale factor,
      registration-weighted PRR produced significantly higher contrast-to-noise ratio
      (CNR) for each lesion than PRR (p < 0.001), with average lesion CNR increasing
      significantly from (2.10 +/- 0.05) to (2.70 +/- 0.06) for 3 mm postsmoothing (p <
      0.001) and from (2.03 +/- 0.06) to (2.77 +/- 0.05) for 6 mm postsmoothing (p <
      0.001). Likewise, for MCIR registration weighting significantly increased the
      average CNR from (2.38 +/- 0.04) to (2.62 +/- 0.07) for 3 mm postsmoothing (p <
      0.001) and from (2.56 +/- 0.05) to (2.84 +/- 0.08) for 6 mm postsmoothing (p <
      0.001). These gains in lesion CNR were obtained despite corresponding reductions
      in signal-to-noise ratio, as expected from the use of unequal weighting of gated
      data with comparable variance. CONCLUSIONS: Registration weighting can
      significantly improve lesion CNR in motion corrected images, especially for PRR.

PMID- 22380358
TI  - Photon energy-modulated radiotherapy: Monte Carlo simulation and treatment
      planning study.
AB  - PURPOSE: To demonstrate the feasibility of photon energy-modulated radiotherapy
      during beam-on time. METHODS: A cylindrical device made of aluminum was
      conceptually proposed as an energy modulator. The frame of the device was
      connected with 20 tubes through which mercury could be injected or drained to
      adjust the thickness of mercury along the beam axis. In Monte Carlo (MC)
      simulations, a flattening filter of 6 or 10 MV linac was replaced with the
      device. The thickness of mercury inside the device varied from 0 to 40 mm at the
      field sizes of 5 * 5 cm(2) (FS5), 10 * 10 cm(2) (FS10), and 20 * 20 cm(2) (FS20).
      At least 5 billion histories were followed for each simulation to create phase
      space files at 100 cm source to surface distance (SSD). In-water beam data were
      acquired by additional MC simulations using the above phase space files. A
      treatment planning system (TPS) was commissioned to generate a virtual machine
      using the MC-generated beam data. Intensity modulated radiation therapy (IMRT)
      plans for six clinical cases were generated using conventional 6 MV, 6 MV
      flattening filter free, and energy-modulated photon beams of the virtual machine.
      RESULTS: As increasing the thickness of mercury, Percentage depth doses (PDD) of
      modulated 6 and 10 MV after the depth of dose maximum were continuously
      increased. The amount of PDD increase at the depth of 10 and 20 cm for modulated
      6 MV was 4.8% and 5.2% at FS5, 3.9% and 5.0% at FS10 and 3.2%-4.9% at FS20 as
      increasing the thickness of mercury from 0 to 20 mm. The same for modulated 10 MV
      was 4.5% and 5.0% at FS5, 3.8% and 4.7% at FS10 and 4.1% and 4.8% at FS20 as
      increasing the thickness of mercury from 0 to 25 mm. The outputs of modulated 6
      MV with 20 mm mercury and of modulated 10 MV with 25 mm mercury were reduced into
      30%, and 56% of conventional linac, respectively. The energy-modulated IMRT plans
      had less integral doses than 6 MV IMRT or 6 MV flattening filter free plans for
      tumors located in the periphery while maintaining the similar quality of target
      coverage, homogeneity, and conformity. CONCLUSIONS: The MC study for the designed
      energy modulator demonstrated the feasibility of energy-modulated photon beams
      available during beam-on time. The planning study showed an advantage of energy
      and intensity modulated radiotherapy in terms of integral dose without
      sacrificing any quality of IMRT plan.

PMID- 22380359
TI  - Neutron dose equivalent measured at the maze door with various openings for the
      jaws and MLC.
AB  - PURPOSE: This study was undertaken to explore the effects of the jaws and the MLC
      openings on the neutron dose equivalent (DE) at the maze door and neutron flux at
      the patient plane. METHODS: The neutron dose equivalent was measured at the maze
      entrance door of a 15 MV therapy linear accelerator room. All measurements were
      performed using various field sizes up to 40 cm * 40 cm. Activation detectors
      constructed from natural Indium (In) were exposed at Cd envelope to neutrons in
      order to estimate relative changes of epithermal neutron fluences in the patient
      plane. RESULTS: Our study showed that the dose equivalent at the maze door is at
      the highest when the jaw are closed and that maximal jaws opening reduces the DE
      by more than 20%. The neutron dose equivalent at the maze door measured for
      radiation fields defined by jaws do not differ significantly from the DE measured
      when MLC determines the same size radiation field. The epithermal capture
      reaction rate measured using different jaw openings differs by approximately 10%.
      When an MLC leaf is inserted into a fixed geometry for one opening of the jaws,
      an increase of the epithermal neutron capture reaction rate in Indium activation
      detectors was observed. CONCLUSIONS: There is no significant difference in the
      neutron DE when MLC defines radiation field instead of jaws. This leads to the
      conclusion that the overall number of neutrons remains similar and it does not
      depend on how primary photon beam was stopped-by the jaws or the MLC. An increase
      of the fast neutron capture reaction rate when MLC leaves are inserted probably
      originates from the neutron scattering.

PMID- 22380360
TI  - Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular
      alpha therapy.
AB  - PURPOSE: Metastatic melanoma lesions experienced marked regression after systemic
      targeted alpha therapy in a phase 1 clinical trial. This unexpected response was
      ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor
      regression is achieved by killing endothelial cells (ECs) in tumor capillaries
      and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this
      paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT
      by building up the testing Monte Carlo microdosimetric models. METHODS: Geant4
      was adapted to simulate the spatial nonuniform distribution of the alpha emitter
      (213)Bi. The intraluminal model was designed to simulate the background dose to
      normal tissue capillary ECs from the nontargeted activity in the blood. The
      perivascular model calculates the EC dose from the activity bound to the
      perivascular cancer cells. The key parameters are the probability of an alpha
      particle traversing an EC nucleus, the energy deposition, the lineal energy
      transfer, and the specific energy. These results were then applied to interpret
      the clinical trial. Cell survival rate and therapeutic gain were determined.
      RESULTS: The specific energy for an alpha particle hitting an EC nucleus in the
      intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the
      average probability of traversal in these models is 2.7% and 1.1%, the mean
      specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that
      the source distribution has a significant impact on the dose. Using the melanoma
      clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be
      3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a
      maximum therapeutic gain of about 180 and validate the TAVAT concept.
      CONCLUSIONS: TAVAT can deliver a cytotoxic dose to tumor capillaries without
      being toxic to normal tissue capillaries.

PMID- 22380361
TI  - Breast composition measurement with a cadmium-zinc-telluride based spectral
      computed tomography system.
AB  - PURPOSE: To investigate the feasibility of breast tissue composition in terms of
      water, lipid, and protein with a cadmium-zinc-telluride (CZT) based computed
      tomography (CT) system to help better characterize suspicious lesions. METHODS:
      Simulations and experimental studies were performed using a spectral CT system
      equipped with a CZT-based photon-counting detector with energy resolution.
      Simulations of the figure-of-merit (FOM), the signal-to-noise ratio (SNR) of the
      dual energy image with respect to the square root of mean glandular dose (MGD),
      were performed to find the optimal configuration of the experimental acquisition
      parameters. A calibration phantom 3.175 cm in diameter was constructed from
      polyoxymethylene plastic with cylindrical holes that were filled with water and
      oil. Similarly, sized samples of pure adipose and pure lean bovine tissues were
      used for the three-material decomposition. Tissue composition results computed
      from the images were compared to the chemical analysis data of the tissue
      samples. RESULTS: The beam energy was selected to be 100 kVp with a splitting
      energy of 40 keV. The tissue samples were successfully decomposed into water,
      lipid, and protein contents. The RMS error of the volumetric percentage for the
      three-material decomposition, as compared to data from the chemical analysis, was
      estimated to be approximately 5.7%. CONCLUSIONS: The results of this study
      suggest that the CZT-based photon-counting detector may be employed in the CT
      system to quantify the water, lipid, and protein mass densities in tissue with a
      relatively good agreement.

PMID- 22380362
TI  - Is there a single spot size and grid for intensity modulated proton therapy?
      Simulation of head and neck, prostate and mesothelioma cases.
AB  - PURPOSE: To assess the quality of dose distributions in real clinical cases for
      different dimensions of scanned proton pencil beams. The distance between spots
      (i.e., the grid of delivery) is optimized for each dimension of the pencil beam.
      METHODS: The authors vary the sigma of the initial Gaussian size of the spot,
      from sigma(x) = sigma(y) = 3 mm to sigma(x) = sigma(y) = 8 mm, to evaluate the
      impact of the proton beam size on the quality of intensity modulated proton
      therapy (IMPT) plans. The distance between spots, Deltax and Deltay, is optimized
      on the spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with
      the best spot grid resolution). In our Hyperion treatment planning system (TPS),
      constrained optimization is applied with respect to the organs at risk (OARs),
      i.e., the optimization tries to satisfy the dose objectives in the planning
      target volume (PTV) as long as all planning objectives for the OARs are met.
      Three-field plans for a nasopharynx case, two-field plans for a prostate case,
      and two-field plans for a malignant pleural mesothelioma case are considered in
      our analysis. RESULTS: For the head and neck tumor, the best grids (i.e.,
      distance between spots) are 5, 4, 6, 6, and 8 mm for sigma = 3, 4, 5, 6, and 8
      mm, respectively. sigma <= 5 mm is required for tumor volumes with low dose and
      sigma <= 4 mm for tumor volumes with high dose. For the prostate patient, the
      best grid is 4, 4, 5, 5, and 5 mm for sigma = 3, 4, 5, 6, and 8 mm, respectively.
      Beams with sigma > 3 mm did not satisfy our first clinical requirement that 95%
      of the prescribed dose is delivered to more than 95% of prostate and proximal
      seminal vesicles PTV. Our second clinical requirement, to cover the distal
      seminal vesicles PTV, is satisfied for beams as wide as sigma = 6 mm. For the
      mesothelioma case, the low dose PTV prescription is well respected for all values
      of sigma, while there is loss of high dose PTV coverage for sigma > 5 mm. The
      best grids have a spacing of 6, 7, 8, 9, and 12 mm for sigma = 3, 4, 5, 6, and 8
      mm, respectively. CONCLUSIONS: The maximum acceptable proton pencil beam sigma
      depends on the volume treated, the protocol of delivery, and optimization of the
      plan. For the clinical cases, protocol and optimization used in this analysis,
      acceptable sigmas are <= 4 mm for the head and neck tumor, <= 3 mm for the
      prostate tumor and <= 6 mm for the malignant pleural mesothelioma. One can apply
      the same procedure used in this analysis when given a "class" of patients, a
      sigma and a clinical protocol to determine the optimal grid spacing.

PMID- 22380363
TI  - T(2)* relaxation times of intraductal murine mammary cancer, invasive mammary
      cancer, and normal mammary gland.
AB  - PURPOSE: This study investigates the feasibility of T(2)* to be a diagnostic
      indicator of early breast cancer in a mouse model. T(2)* is sensitive to
      susceptibility effects due to local inhomogeneity of the magnetic field, e.g.,
      caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in
      patients, the characteristics of single mammary ducts containing pure intraductal
      cancer can be evaluated. METHODS: The C3(1)SV40Tag mouse model of breast cancer
      (n = 11) and normal FVB/N mice (n = 6) were used to measure T(2)* of normal
      mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph
      nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High
      resolution (117 microns) axial 2D multislice gradient echo images with fat
      suppression were acquired first to identify inguinal mammary gland. Then a
      multislice multigradient echo pulse sequence with and without fat suppression
      were performed over the inguinal mammary gland. The modulus of a complex double
      exponential decay detected by the multigradient echo sequence was used to fit the
      absolute proton free induction decay averaged over a region of interest to
      determine the T(2)* of water and fat signals. RESULTS: The measured T(2)* values
      of tumor and muscle are similar (~15 ms), and almost twice that of lymph nodes
      (~8 ms). There was a statistically significant difference (p < 0.03) between
      T(2)* in normal mammary tissue (13.7 +/- 2.9 ms) and intraductal cancers (11 +/-
      2.0 ms) when a fat suppression pulse was applied. CONCLUSIONS: These are the
      first reported T(2)* measurements from single mammary ducts. The results
      demonstrated that T(2)* measurements may have utility for identifying early pre
      invasive cancers in mouse models. This may inspire similar research for patients
      using T(2)* for diagnostic imaging of early breast cancer.

PMID- 22380364
TI  - Software-controlled, highly automated intrafraction prostate motion correction
      with intrafraction stereographic targeting: System description and clinical
      results.
AB  - PURPOSE: A new system for software-controlled, highly automated correction of
      intrafraction prostate motion," intrafraction stereographic targeting" (iSGT), is
      described and evaluated. METHODS: At our institute, daily prostate positioning is
      routinely performed at the start of treatment beam using stereographic targeting
      (SGT). iSGT was implemented by extension of the SGT software to facilitate fast
      and accurate intrafraction motion corrections with minimal user interaction. iSGT
      entails megavoltage (MV) image acquisitions with the first segment of selected
      IMRT beams, automatic registration of implanted markers, followed by remote couch
      repositioning to correct for intrafraction motion above a predefined threshold,
      prior to delivery of the remaining segments. For a group of 120 patients, iSGT
      with corrections for two nearly lateral beams was evaluated in terms of workload
      and impact on effective intrafraction displacements in the sagittal plane.
      RESULTS: SDs of systematic (Sigma) and random (sigma) displacements relative to
      the planning CT measured directly after initial SGT setup correction were <0.5
      and <0.8 mm, respectively. Without iSGT corrections, effective Sigma and sigma
      for the 11-min treatments would increase to Sigma(eff) < 1.1 mm and sigma(eff) <
      1.2 mm. With the iSGT procedure with an action level of 4 mm, effective
      positioning errors were reduced to Sigma(eff) < 0.8 mm and sigma(eff) < 1.0 mm,
      with 23.1% of all fractions requiring a correction. Computer simulations
      demonstrated that with an action level of 2 mm, the errors would have been
      reduced to Sigma(eff) < 0.6 mm and sigma(eff) < 0.7 mm, requiring corrections in
      82.4% of the fractions. Because iSGT is highly automated, the extra time added by
      iSGT is <30 s if a correction is required. CONCLUSIONS: Without increasing
      imaging dose, iSGT successfully reduces intrafraction prostate motion with
      minimal workload and increase in fraction time. An action level of 2 mm is
      recommended.

PMID- 22380365
TI  - Automatic tracking of implanted fiducial markers in cone beam CT projection
      images.
AB  - PURPOSE: This paper describes a novel method for simultaneous intrafraction
      tracking of multiple fiducial markers. Although the proposed method is generic
      and can be adopted for a number of applications including fluoroscopy based
      patient position monitoring and gated radiotherapy, the tracking results
      presented in this paper are specific to tracking fiducial markers in a sequence
      of cone beam CT projection images. METHODS: The proposed method is accurate and
      robust thanks to utilizing the mean shift and random sampling principles,
      respectively. The performance of the proposed method was evaluated with
      qualitative and quantitative methods, using data from two pancreatic and one
      prostate cancer patients and a moving phantom. The ground truth, for quantitative
      evaluation, was calculated based on manual tracking preformed by three observers.
      RESULTS: The average dispersion of marker position error calculated from the
      tracking results for pancreas data (six markers tracked over 640 frames, 3840
      marker identifications) was 0.25 mm (at iscoenter), compared with an average
      dispersion for the manual ground truth estimated at 0.22 mm. For prostate data
      (three markers tracked over 366 frames, 1098 marker identifications), the average
      error was 0.34 mm. The estimated tracking error in the pancreas data was < 1 mm
      (2 pixels) in 97.6% of cases where nearby image clutter was detected and in
      100.0% of cases with no nearby image clutter. CONCLUSIONS: The proposed method
      has accuracy comparable to that of manual tracking and, in combination with the
      proposed batch postprocessing, superior robustness. Marker tracking in cone beam
      CT (CBCT) projections is useful for a variety of purposes, such as providing data
      for assessment of intrafraction motion, target tracking during rotational
      treatment delivery, motion correction of CBCT, and phase sorting for 4D CBCT.

PMID- 22380366
TI  - Accuracy of the electron transport in mcnp5 and its suitability for ionization
      chamber response simulations: A comparison with the egsnrc and penelope codes.
AB  - PURPOSE: In this work, accuracy of the mcnp5 code in the electron transport
      calculations and its suitability for ionization chamber (IC) response simulations
      in photon beams are studied in comparison to egsnrc and penelope codes. METHODS:
      The electron transport is studied by comparing the depth dose distributions in a
      water phantom subdivided into thin layers using incident energies (0.05, 0.1, 1,
      and 10 MeV) for the broad parallel electron beams. The IC response simulations
      are studied in water phantom in three dosimetric gas materials (air, argon, and
      methane based tissue equivalent gas) for photon beams ((60)Co source, 6 MV linear
      medical accelerator, and mono-energetic 2 MeV photon source). Two optional
      electron transport models of mcnp5 are evaluated: the ITS-based electron energy
      indexing (mcnp5(ITS)) and the new detailed electron energy-loss straggling logic
      (mcnp5(new)). The electron substep length (ESTEP parameter) dependency in mcnp5
      is investigated as well. RESULTS: For the electron beam studies, large
      discrepancies (>3%) are observed between the MCNP5 dose distributions and the
      reference codes at 1 MeV and lower energies. The discrepancy is especially
      notable for 0.1 and 0.05 MeV electron beams. The boundary crossing artifacts,
      which are well known for the mcnp5(ITS), are observed for the mcnp5(new) only at
      0.1 and 0.05 MeV beam energies. If the excessive boundary crossing is eliminated
      by using single scoring cells, the mcnp5(ITS) provides dose distributions that
      agree better with the reference codes than mcnp5(new). The mcnp5 dose estimates
      for the gas cavity agree within 1% with the reference codes, if the mcnp5(ITS) is
      applied or electron substep length is set adequately for the gas in the cavity
      using the mcnp5(new). The mcnp5(new) results are found highly dependent on the
      chosen electron substep length and might lead up to 15% underestimation of the
      absorbed dose. CONCLUSIONS: Since the mcnp5 electron transport calculations are
      not accurate at all energies and in every medium by general clinical standards,
      caution is needed, if mcnp5 is used with the current electron transport models
      for dosimetric applications.

PMID- 22380367
TI  - A real-time respiration position based passive breath gating equipment for gated
      radiotherapy: a preclinical evaluation.
AB  - PURPOSE: To develop a passive gating system incorporating with the real-time
      position management (RPM) system for the gated radiotherapy. METHODS: Passive
      breath gating (PBG) equipment, which consists of a breath-hold valve, a
      controller mechanism, a mouthpiece kit, and a supporting frame, was designed. A
      commercial real-time positioning management system was implemented to synchronize
      the target motion and radiation delivery on a linear accelerator with the
      patient's breathing cycle. The respiratory related target motion was investigated
      by using the RPM system for correlating the external markers with the internal
      target motion while using PBG for passively blocking patient's breathing. Six
      patients were enrolled in the preclinical feasibility and efficiency study of the
      PBG system. RESULTS: PBG equipment was designed and fabricated. The PBG can be
      manually triggered or released to block or unblock patient's breathing. A
      clinical workflow was outlined to integrate the PBG with the RPM system. After
      implementing the RPM based PBG system, the breath-hold period can be prolonged to
      15-25 s and the treatment delivery efficiency for each field can be improved by
      200%-400%. The results from the six patients showed that the diaphragm motion
      caused by respiration was reduced to less than 3 mm and the position of the
      diaphragm was reproducible for difference gating periods. CONCLUSIONS: A RPM
      based PBG system was developed and implemented. With the new gating system, the
      patient's breath-hold time can be extended and a significant improvement in the
      treatment delivery efficiency can also be achieved.

PMID- 22380368
TI  - Pretreatment quality assurance of flattening filter free beams on 224 patients
      for intensity modulated plans: a multicentric study.
AB  - PURPOSE: Pretreatment quality assurance data from four centers, members of the
      European TrueBeam council were analyzed with different verification devices to
      assess reliability of flattening filter free beam delivery for intensity
      modulated radiotherapy (IMRT) and RapidArc (RA) techniques. METHODS:
      TrueBeam((r)) (Varian Medical System) is a new linear accelerator designed for
      delivering flattened, as well as flattening filter free beams. Pretreatment
      dosimetric validation of plan delivery was performed with different verification
      devices and responses to high dose rates were tested. Treatment planning was done
      in Eclipse planning system (PRO 8.9, AAA 8.9). gamma evaluation was performed
      with (dose difference) = 3% and (distance to agreement) = 3 mm scoring the gamma
      agreement index (GAI, % of field area passing the test). Two hundred and twenty
      four patients with 1-6 lesions in various anatomical regions and dose per
      fraction ranging from 1.8 Gy to 25 Gy were included in the study; 88 were treated
      with 6 MV flattening filter free (X6FFF) beam energy and 136 with 10 MV
      flattening filter free (X10FFF) beam. Gafchromic films in solid water, delta(4),
      arccheck, and matrixx phantom were used to verify the dose distributions.
      Additionally, point measurements were performed using a PinPoint chamber and a
      Farmer chamber. RESULTS: Dose calculation as well as dose delivery was equally
      accurate for IMRT and RA delivery (IMRT: GAI = 99.3% (+/-1.1); RA: GAI = 98.8%
      (+/-1.1) as well as for the two beams evaluated (X6FFF: GAI = 99.1% (+/-1.0);
      X10FFF: GAI = 98.8% (+/-1.2). Only small differences were found for the four
      verification devices. A point dose verification was performed on 52 cases,
      obtaining a dose deviation of 0.34%. The GAI variations with number of monitor
      units were statistically significant. CONCLUSIONS: The TrueBeam FFF modality,
      analyzed with a variety of verification devices and planned with Eclipse planning
      system is dosimetrically accurate (within the specified limits 3 mm/3%) for both
      X6FFF and X10FFF beam energy.

PMID- 22380369
TI  - Analysis of biological tissues in infant chest for the development of an
      equivalent radiographic phantom.
AB  - PURPOSE: The main purpose of the present study was to determine the amounts of
      different tissues in the chest of the newborn patient (age <=1 year), with the
      aim of developing a homogeneous phantom chest equivalent. This type of phantom is
      indispensable in the development of optimization procedures for radiographic
      techniques, including dosimetric control, which is a crucial aspect of pediatric
      radiology. The authors present a systematic set of procedures, including a
      computational algorithm, to estimate the amounts of tissues and thicknesses of
      the corresponding simulator material plates used to construct the phantom.
      METHODS: The Gaussian fit of computed tomographic (CT) analysis was applied to
      classify and quantify different biological tissues. The methodology is summarized
      with a computational algorithm, which was used to quantify tissues through
      automated CT analysis. The thicknesses of the equivalent homogeneous simulator
      material plates were determined to construct the phantom. RESULTS: A total of 180
      retrospective CT examinations with anterior-posterior diameter values ranging 8.5
      13.0 cm were examined. The amounts of different tissues were evaluated. The
      results provided elements to construct a phantom to simulate the infant chest in
      the posterior-anterior or anterior-posterior (PA/AP) view. CONCLUSIONS: To our
      knowledge, this report represents the first demonstration of an infant chest
      phantom dedicated to the radiology of children younger than one year. This
      phantom is a key element in the development of clinical charts for optimizing
      radiographic technique in pediatric patients. Optimization procedures for
      nonstandard patients were reported previously [Pina et al., Phys. Med. Biol. 49,
      N215-N226 (2004) and Pina et al., Appl. Radiat. Isot. 67, 61-69 (2009)]. The
      constructed phantom represents a starting point to obtain radiologic protocols
      for the infant patient.

PMID- 22380370
TI  - Liver segmentation in contrast enhanced CT data using graph cuts and interactive
      3D segmentation refinement methods.
AB  - PURPOSE: Liver segmentation is an important prerequisite for the assessment of
      liver cancer treatment options like tumor resection, image-guided radiation
      therapy (IGRT), radiofrequency ablation, etc. The purpose of this work was to
      evaluate a new approach for liver segmentation. METHODS: A graph cuts
      segmentation method was combined with a three-dimensional virtual reality based
      segmentation refinement approach. The developed interactive segmentation system
      allowed the user to manipulate volume chunks and/or surfaces instead of 2D
      contours in cross-sectional images (i.e, slice-by-slice). The method was
      evaluated on twenty routinely acquired portal-phase contrast enhanced multislice
      computed tomography (CT) data sets. An independent reference was generated by
      utilizing a currently clinically utilized slice-by-slice segmentation method.
      After 1 h of introduction to the developed segmentation system, three experts
      were asked to segment all twenty data sets with the proposed method. RESULTS:
      Compared to the independent standard, the relative volumetric segmentation
      overlap error averaged over all three experts and all twenty data sets was 3.74%.
      Liver segmentation required on average 16 min of user interaction per case. The
      calculated relative volumetric overlap errors were not found to be significantly
      different [analysis of variance (ANOVA) test, p = 0.82] between experts who
      utilized the proposed 3D system. In contrast, the time required by each expert
      for segmentation was found to be significantly different (ANOVA test, p =
      0.0009). Major differences between generated segmentations and independent
      references were observed in areas were vessels enter or leave the liver and no
      accepted criteria for defining liver boundaries exist. In comparison, slice-by
      slice based generation of the independent standard utilizing a live wire tool
      took 70.1 min on average. A standard 2D segmentation refinement approach applied
      to all twenty data sets required on average 38.2 min of user interaction and
      resulted in statistically not significantly different segmentation error indices
      (ANOVA test, significance level of 0.05). CONCLUSIONS: All three experts were
      able to produce liver segmentations with low error rates. User interaction time
      savings of up to 71% compared to a 2D refinement approach demonstrate the utility
      and potential of our approach. The system offers a range of different tools to
      manipulate segmentation results, and some users might benefit from a longer
      learning phase to develop efficient segmentation refinement strategies. The
      presented approach represents a generally applicable segmentation approach that
      can be applied to many medical image segmentation problems.

PMID- 22380371
TI  - Toward a practical template-based approach to semiquantitative SPECT myocardial
      perfusion imaging.
AB  - PURPOSE: Our template-based quantitative perfusion single photon emission
      computed tomography (SPECT) method (T-QPS) performs semiquantitative analysis for
      myocardial perfusion imaging (MPI) without the use of normal databases. However,
      in its current form, T-QPS requires extensive calculations, which limits its
      clinical application. In the interest of clinical feasibility, the authors
      examine the trade-off between accuracy and processing time as the method is
      simplified. METHODS: The T-QPS method uses the reconstructed SPECT image of the
      patient to create a 3D digital template of his/her healthy heart. This template
      is then projected, reconstructed, and sampled into the bulls-eye map domain. A
      ratio of the patient and template images produces a final corrected image in
      which a threshold is applied to identify perfusion defects. In principle, the
      template should be constructed with the heart and all extracardiac activity, and
      the projection step should include primary and scatter components; however, this
      leads to lengthy calculations. In an attempt to shorten the processing time, the
      authors analyzed the performance of four template (T) generation methods: T(P
      HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG), where P and S represent primary
      and scattered photons included in the projection step, respectively; and HRT and
      HRTBKG represent template constructed with the heart only and the heart with
      background activity, respectively. Forty-eight thorax phantoms and 21 randomly
      selected patient studies were analyzed using each approach. All studies used GE's
      Infinia Hawkeye SPECT/CT system and followed a standard cardiac acquisition
      protocol. RESULTS: Approximate processing times for the T(P-HRT), T(PS-HRT), T(P
      HRTBKG), and T(PS-HRTBKG) methods were less than a minute, 2-3 h, less than a
      minute and 3-4 h, respectively. In both the simulation and patient studies, a
      significant reduction in the quality of perfusion defect definition was exhibited
      by the T(P-HRT) method relative to the other three methods. The optimal method
      with respect to perfusion defect definition and processing time was T(P-HRTBKG)
      with a sensitivity, specificity, and accuracy in spatially defining the perfusion
      defects (simulation study) of 80%, 84%, and 83%, respectively. CONCLUSIONS: The T
      QPS method using T(P-HRTBKG) leads to accurate and fast semiquantitative analysis
      of SPECT MPI, without the use of normal databases.

PMID- 22380372
TI  - The use and QA of biologically related models for treatment planning: short
      report of the TG-166 of the therapy physics committee of the AAPM.
AB  - Treatment planning tools that use biologically related models for plan
      optimization and/or evaluation are being introduced for clinical use. A variety
      of dose-response models and quantities along with a series of organ-specific
      model parameters are included in these tools. However, due to various
      limitations, such as the limitations of models and available model parameters,
      the incomplete understanding of dose responses, and the inadequate clinical data,
      the use of biologically based treatment planning system (BBTPS) represents a
      paradigm shift and can be potentially dangerous. There will be a steep learning
      curve for most planners. The purpose of this task group is to address some of
      these relevant issues before the use of BBTPS becomes widely spread. In this
      report, the authors (1) discuss strategies, limitations, conditions, and cautions
      for using biologically based models and parameters in clinical treatment
      planning; (2) demonstrate the practical use of the three most commonly used
      commercially available BBTPS and potential dosimetric differences between
      biologically model based and dose-volume based treatment plan optimization and
      evaluation; (3) identify the desirable features and future directions in
      developing BBTPS; and (4) provide general guidelines and methodology for the
      acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.

PMID- 22380373
TI  - Dose reduction in LDR brachytherapy by implanted prostate gold fiducial markers.
AB  - PURPOSE: The dosimetric impact of gold fiducial markers (FM) implanted prior to
      external beam radiotherapy of prostate cancer on low dose rate (LDR)
      brachytherapy seed implants performed in the context of combined therapy was
      investigated. METHODS: A virtual water phantom was designed containing a single
      FM. Single and multi source scenarios were investigated by performing Monte Carlo
      dose calculations, along with the influence of varying orientation and distance
      of the FM with respect to the sources. Three prostate cancer patients treated
      with LDR brachytherapy for a recurrence following external beam radiotherapy with
      implanted FM were studied as surrogate cases to combined therapy. FM and
      brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose
      calculations were performed with and without FM. The dosimetric impact of the FM
      was evaluated by quantifying the amplitude of dose shadows and the volume of cold
      spots. D(90) was reported based on the post implant CT prostate contour. RESULTS:
      Large shadows are observed in the single source-FM scenarios. As expected from
      geometric considerations, the shadows are dependent on source-FM distance and
      orientation. Large dose reductions are observed at the distal side of FM, while
      at the proximal side a dose enhancement is observed. In multisource scenarios,
      the importance of shadows appears mitigated, although FM at the periphery of the
      seed distribution caused underdosage (<prescription dose). In clinical cases, the
      FM reduced the dose to some voxels by up to 50% and generated shadows with
      extents of the order of 4 mm. Within the prostate contour, cold spots (<95%
      prescription dose) of the order of 20 mm(3) were observed. D(90) proved
      insensitive to the presence of FM for the cases selected. CONCLUSIONS: There is a
      major local impact of FM present in LDR brachytherapy seed implant dose
      distributions. Therefore, reduced tumor control could be expected from FM
      implanted in tumors, although our results are too limited to draw conclusions
      regarding clinical significance.

PMID- 22380374
TI  - EXACTRAC x-ray and beam isocenters-what's the difference?
AB  - PURPOSE: To evaluate the geometric accuracy of the isocenter of an image-guidance
      system, as implemented in the exactrac system from brainlab, relative to the
      linear accelerator radiation isocenter. Subsequently to correct the x-ray
      isocenter of the exactrac system for any geometric discrepancies between the two
      isocenters. METHODS: Five Varian linear accelerators all equipped with electronic
      imaging devices and exactrac with robotics from brainlab were evaluated. A
      commercially available Winston-Lutz phantom and an in-house made adjustable base
      were used in the setup. The electronic portal imaging device of the linear
      accelerators was used to acquire MV-images at various gantry angles. Stereoscopic
      pairs of x-ray images were acquired using the exactrac system. The deviation
      between the position of the external laser isocenter and the exactrac isocenter
      was evaluated using the commercial software of the exactrac system. In-house
      produced software was used to analyze the MV-images and evaluate the deviation
      between the external laser isocenter and the radiation isocenter of the linear
      accelerator. Subsequently, the deviation between the radiation isocenter and the
      isocenter of the exactrac system was calculated. A new method of calibrating the
      isocenter of the exactrac system was applied to reduce the deviations between the
      radiation isocenter and the exactrac isocenter. RESULTS: To evaluate the
      geometric accuracy a 3D deviation vector was calculated for each relative
      isocenter position. The 3D deviation between the external laser isocenter and the
      isocenter of the exactrac system varied from 0.21 to 0.42 mm. The 3D deviation
      between the external laser isocenter and the linac radiation isocenter ranged
      from 0.37 to 0.83 mm. The 3D deviation between the radiation isocenter and the
      isocenter of the exactrac system ranged from 0.31 to 1.07 mm. Using the new
      method of calibrating the exactrac isocenter the 3D deviation of one linac was
      reduced from 0.90 to 0.23 mm. The results were complicated due to routine
      maintenance of the linac, including laser calibration. It was necessary to repeat
      the measurements in order to perform the calibration of the exactrac isocenter.
      CONCLUSIONS: The deviations between the linac radiation isocenter and the
      exactrac isocenter were of an order that may have clinical relevance. An
      alternative method of calibrating the isocenter of the exactrac system was
      applied and reduced the deviations between the two isocenters.

PMID- 22380375
TI  - Determining the effects of microsphere and surrounding material composition on
      (90)Y dose kernels using egsnrc and mcnp5.
AB  - PURPOSE: Recent advances in the imaging of (90)Y using positron emission
      tomography (PET) and improved uncertainty in the branching ratio for the internal
      pair production component of (90)Y decay allow for a more accurate determination
      of the activity distribution of (90)Y microspheres within a patient. This
      improved activity distribution can be convolved with the dose kernel of (90)Y to
      calculate the dose distribution within a patient. This work investigates the
      effects of microsphere and surrounding material composition on (90)Y dose kernels
      using egsnrc and mcnp5 and compares the results of these two transport codes.
      METHODS: Monte Carlo simulations were performed with egsnrc and mcnp5 to
      calculate the dose rate at multiple radial distances around various (90)Y
      sources. Point source simulations were completed with mcnp5 to determine the
      optimal electron transport settings for this work. After determining the optimal
      settings, point source simulations were completed using egsnrc (user code edknrc)
      and mcnp5 in water and liver [as defined by the International Commission on
      Radiation Units and Measurements (ICRU) Report 44]. The results were compared to
      ICRU Report 72 reference data. Point source simulations were also completed in
      water with a density of 1.06 g[middle dot]cm(-3) to evaluate the effect of the
      density of the surrounding material. Glass and resin microsphere simulations were
      performed with average and maximum diameter and density values (based on values
      given in the literature) in water and in liver. The results were compared to
      point source simulation results using the same transport code and in the same
      surrounding material. All simulations had statistical uncertainties less than 1%.
      RESULTS: The optimal transport settings in mcnp5 for this work included using the
      energy-and step-specific algorithm (DBCN 17J 2) and ESTEP set to 10. These
      settings were used for all subsequent simulations with mcnp5. The point source
      simulations in water for both egsnrc and mcnp5 were found to agree within 2% of
      the ICRU 72 reference data over the investigated range. Point source simulations
      in liver had large differences relative to ICRU 72, approaching -60% near the
      maximum range of (90)Y. These differences are mostly attributed to the difference
      in density between water (1.0 g[middle dot]cm(-3)) and liver (1.06 g[middle
      dot]cm(-3)). Glass and resin microsphere simulations showed a slight decrease in
      the dose rate near the maximum range of (90)Y relative to the point source
      simulations. The largest relative differences were approximately -4.2% and -2.8%
      for the glass and resin microspheres, respectively. Agreement between the egsnrc
      and mcnp5 simulations results was generally good. CONCLUSIONS: The presence of
      the microsphere material causes slight differences in the (90)Y dose kernel
      compared to those calculated with point sources. Large differences were seen
      between simulations in water and those in liver. For the most accurate
      calculation of the dose distribution, the density of the patient's liver should
      be accounted for in the calculation of the dose kernel. Lastly, due to the need
      to determine the optimal transport settings with mcnp5, electron transport with
      this code should be used with caution.

PMID- 22380376
TI  - Anatomical complexity in breast parenchyma and its implications for optimal
      breast imaging strategies.
AB  - PURPOSE: The purpose of this investigation was to assess the anatomical noise in
      breast images using a mathematically derived parameter beta as a surrogate for
      detection performance, across the same patient cohort but in different imaging
      modalities including mammography, tomosynthesis, and breast CT. METHODS: Women
      who were scheduled for breast biopsy were approached for participation in this
      IRB and HIPPA-compliant investigation. A total of 23 women had all views of each
      modality and represent the cohort studied in this investigation. Image data sets
      across all modalities were analyzed using 1000 regions of interest per image data
      set, and the anatomical noise power spectrum, NPS(a)(f), was computed and
      averaged for each breast image data set. After windowing the total noise power
      spectrum NPS(t)(f) to a specific frequency range corresponding to anatomical
      noise, the power-law slope (beta) of the NPS(a)(f) was computed where NPS(a)(f) =
      alpha f(-) (beta). RESULTS: The value of beta was determined for breast CT data
      sets, and they were 1.75 (0.424), 1.83 (0.352), and 1.79 (0.397), for the
      coronal, sagittal, and axial views, respectively. For tomosynthesis, beta was
      3.06 (0.361) and 3.10 (0.315) for the craniocaudal (CC) and medial lateral
      oblique (MLO) views, respectively. For mammography, these values were 3.17
      (0.226) and 3.30 (0.236), for the CC and MLO views, respectively. The values of
      beta for breast CT were significantly different than those for tomosynthesis and
      mammography (p < 0.001, all 12 comparisons). CONCLUSIONS: Based on the parameter
      beta which is thought to describe anatomical noise in breast images, breast CT
      was shown to have a statistically significant lower beta than mammography or
      tomosynthesis. It has been suggested in the literature that a lower beta may
      correspond to increased cancer detection performance; however, this has yet to be
      demonstrated unequivocally.

PMID- 22380377
TI  - A novel technique for markerless, self-sorted 4D-CBCT: feasibility study.
AB  - PURPOSE: Four-dimensional CBCT (4D-CBCT) imaging in the treatment room can
      provide verification of moving targets, facilitating the potential for margin
      reduction and consequent dose escalation. Reconstruction of 4D-CBCT images
      requires correlation of respiratory phase with projection acquisition, which is
      often achieved with external surrogate measures of respiration. However, external
      measures may not be a direct representation of the motion of the internal anatomy
      and it is therefore the aim of this work to develop a novel technique for
      markerless, self-sorted 4D-CBCT reconstruction. METHODS: A novel 4D-CBCT
      reconstruction technique based on the principles of Fourier transform (FT) theory
      was investigated for markerless extraction of respiratory phase directly from
      projection data. In this FT technique, both phase information (FT-phase) and
      magnitude information (FT-magnitude) were separately implemented in order to
      discern projections corresponding to peak inspiration, which then facilitated the
      proceeding sort and bin processes involved in retrospective 4D image
      reconstruction. In order to quantitatively evaluate the accuracy of the Fourier
      methods, peak-inspiration projections identified each by FT-phase and FT
      magnitude were compared to those manually identified by visual tracking of
      structures. The average phase difference as assigned by each method vs the manual
      technique was calculated per projection dataset. The percentage of projections
      that were assigned within 10% phase of each other was also computed. Both Fourier
      methods were tested on two phantom datasets, programmed to exhibit sinusoidal
      respiratory cycles of 2.0 cm in amplitude with respiratory cycle lengths of 3 and
      6 s, respectively. Additionally, three sets of patient projections were studied.
      All of the data were previously acquired at slow-gantry speeds ranging between
      0.6 degrees /s and 0.7 degrees /s over a 200 degrees  rotation. Ten phase bins
      with 10% phase windows were selected for 4D-CBCT reconstruction of one phantom
      and one patient case for visual and quantitative comparison. Line profiles were
      plotted for the 0% and 50% phase images as reconstructed by the manual technique
      and each of the Fourier methods. RESULTS: As compared with the manual technique,
      the FT-phase method resulted in average phase differences of 1.8% for the phantom
      with the 3 s respiratory cycle, 3.9% for the phantom with the 6 s respiratory
      cycle, 2.9% for patient 1, 5.0% for patient 2, and 3.8% for patient 3. For the FT
      magnitude method, these numbers were 2.1%, 4.0%, 2.9%, 5.3%, and 3.5%,
      respectively. The percentage of projections that were assigned within 10% phase
      by the FT-phase method as compared to the manual technique for the five datasets
      were 100.0%, 100.0%, 97.6%, 93.4%, and 94.1%, respectively, whereas for the FT
      magnitude method these percentages were 98.1%, 92.3%, 98.7%, 87.3%, and 95.7%.
      Reconstructed 4D phase images for both the phantom and patient case were visually
      and quantitatively equivalent between each of the Fourier methods vs the manual
      technique. CONCLUSIONS: A novel technique employing the basics of Fourier
      transform theory was investigated and demonstrated to be feasible in achieving
      markerless, self-sorted 4D-CBCT reconstruction.

PMID- 22380378
TI  - Least-error projection sorting to optimize retrospectively gated cardiac micro-CT
      of free-breathing mice.
AB  - PURPOSE: To develop and characterize a technique for optimizing image quality by
      eliminating streaking artifacts in retrospectively gated microcomputed tomography
      (micro-CT) images of mice caused by insufficient and irregular angular sampling.
      METHODS: A least-error sorting technique was developed to minimize streak
      artifacts in retrospectively gated cardiac micro-CT images. To ensure complete
      filling of projection space, for each angular position, the projection acquired
      closest to the desired cardiac phase is used to reconstruct a volumetric image.
      An acrylic slanted-edge phantom undergoing cyclic motion was used to characterize
      the system's resolution. The phantom was scanned using a volumetric micro-CT
      scanner equipped with a flat-panel detector mounted on a slip-ring gantry.
      Projection images of the moving phantom were collected over a period of 60 s
      using a variety of acquisition protocols with the rotation period of the gantry
      ranging from 1 to 5 s. The modulation transfer function (MTF) of the
      reconstructed images was measured for many combinations of acquisition and
      reconstruction parameters. The use of the least-error technique was also
      demonstrated in vivo. RESULTS: The motion blurring introduced into the images at
      physiologically significant velocities of 6 cm/s agreed well with predicted
      values; limiting resolution (frequency at 10% MTF) degraded from 2.5 to 1.0 mm(
      1) for a velocity of 6 cm/s and 5 s/rotation gantry speed. Faster gantry rotation
      speeds led to improved temporal resolution but the scanner's data storage and
      transfer rates and field of view limitations made scanning at gantry speeds
      faster than 2 s/rotation impractical. CONCLUSIONS: The least-error technique
      effectively eliminates streaking artifact caused by missing views and allows for
      optimization of image quality in retrospectively gated micro-CT.

PMID- 22380379
TI  - Evaluation of S-values and dose distributions for (90)Y, (131)I, (166)Ho, and
      (188)Re in seven lobes of the rat liver.
AB  - PURPOSE: Rats have been widely used in radionuclide therapy research for the
      treatment of hepatocellular carcinoma (HCC). This has created the need to assess
      rat liver absorbed radiation dose. In most dose estimation studies, the rat liver
      is considered as a homogeneous integrated target organ with a tissue composition
      assumed to be similar to that of human liver tissue. However, the rat liver is
      composed of several lobes having different anatomical and chemical
      characteristics. To assess the overall impact on rat liver dose calculation, the
      authors use a new voxel-based rat model with identified suborgan regions of the
      liver. METHODS: The liver in the original cryosectional color images was manually
      segmented into seven individual lobes and subsequently integrated into a voxel
      based computational rat model. Photon and electron particle transport was
      simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S
      values for (90)Y, (131)I, (166)Ho, and (188)Re for the seven liver lobes. The
      effect of chemical composition on organ-specific absorbed dose was investigated
      by changing the chemical composition of the voxel filling liver material.
      Radionuclide-specific absorbed doses at the voxel level were further assessed for
      a small spherical hepatic tumor. RESULTS: The self-absorbed dose for different
      liver lobes varied depending on their respective masses. A maximum difference of
      3.5% was observed for the liver self-absorbed fraction between rat and human
      tissues for photon energies below 100 keV. (166)Ho and (188)Re produce a
      uniformly distributed high dose in the tumor and relatively low absorbed dose for
      surrounding tissues. CONCLUSIONS: The authors evaluated rat liver radiation doses
      from various radionuclides used in HCC treatments using a realistic computational
      rat model. This work contributes to a better understanding of all aspects
      influencing radiation transport in organ-specific radiation dose evaluation for
      preclinical therapy studies, from tissue composition to organ morphology and
      activity distribution.

PMID- 22380380
TI  - On charged particle equilibrium violation in external photon fields.
AB  - PURPOSE: In a recent paper by Bouchard et al. [Med. Phys. 36(10), 4654-4663
      (2009)], a theoretical model of quality correction factors for idealistic so
      called plan-class specific reference (PCSR) fields was proposed. The reasoning
      was founded on the definition of PCSR fields made earlier by Alfonso et al. [Med.
      Phys. 35(11), 5179-5186 (2008)], requiring the beam to achieve charged particle
      equilibrium (CPE), in a time-averaged sense, in the reference medium. The
      relation obtained by Bouchard et al. was derived using Fano's theorem (1954)
      which states that if CPE is established in a given medium, the dose is
      independent of point-to-point density variations. A potential misconception on
      the achievability of the condition required by Fano (1954) might be responsible
      for false practical conclusions, both in the definition of PCSR fields as well as
      the theoretical model of quality correction factor. METHODS: In this paper, the
      practical achievability of CPE in external beams is treated in detail. The fact
      that this condition is not achievable in single or composite deliveries is
      illustrated by an intuitive method and is also formally demonstrated.
      CONCLUSIONS: Fano's theorem is not applicable in external beam radiation
      dosimetry without (virtually) removing attenuation effects, and therefore, the
      relation conditionally defined by Bouchard et al. (2009) cannot be valid in
      practice. A definition of PCSR fields in the recent formalism for nonstandard
      beams proposed by Alfonso et al. (2008) should be modified, revising the
      criterion of CPE condition. The authors propose reconsidering the terminology
      used to describe standard and nonstandard beams. The authors argue that quality
      correction factors of intensity modulated radiation therapy PCSR fields (i.e.,
      k(Q(pcsr),Q) (f(pcsr),f(ref) )) could be unity under ideal conditions, but it is
      concluded that further investigation is necessary to confirm that hypothesis.

PMID- 22380381
TI  - Evaluation of a lung tumor autocontouring algorithm for intrafractional tumor
      tracking using low-field MRI: a phantom study.
AB  - PURPOSE: The first aim of this study is to investigate the feasibility of online
      autocontouring of tumor in low field MR images (0.2 and 0.5 T) by means of a
      phantom and simulation study for tumor-tracking in linac-MR systems. The second
      aim of this study is to develop an MR compatible, lung tumor motion phantom.
      METHODS: An autocontouring algorithm was developed to determine both the position
      and shape of a lung tumor from each intra fractional MR image. To initiate the
      algorithm, an expert user contours the tumor and its maximum anticipated range of
      motion (herein termed the Background) using pretreatment scan data. During
      treatment, the algorithm processes each intrafractional MR image and
      automatically contours the tumor. To evaluate this algorithm, the authors built a
      phantom that replicates the low field contrast parameters (proton density, T(1),
      T(2)) of lung tumors and healthy lung parenchyma. This phantom allows simulation
      of MR images with the expected lung tumor CNR at 0.2 and 0.5 T by using a single
      3 T scanner. Dynamic bSSFP images (approximately 4 images per second) are
      acquired while the phantom undergoes a series of preprogrammed motions based on
      patient lung tumor motion data. These images are autocontoured off-line using our
      algorithm. The fidelity of autocontouring is assessed by comparing autocontoured
      tumor shape and its centroid position to the actual tumor shape and its position.
      RESULTS: The algorithm successfully contoured the shape of a moving tumor model
      from dynamic MR images acquired every 275 ms. Dice's coefficients of > 0.96 and >
      0.93 are achieved in 0.5 and 0.2 T equivalent images, respectively. Also, the
      algorithm tracked tumor position during dynamic studies, with root mean squared
      error (RMSE) values of < 0.55 and < 0.92 mm for 0.5 and 0.2 T equivalent images,
      respectively. Autocontouring speed is approximately 5 ms for each image.
      CONCLUSIONS: Dice's coefficients of > 0.96 and > 0.93 are achieved between
      autocontoured and real tumor shapes, and the position of a tumor can be tracked
      with RMSE values of < 0.55 and < 0.92 mm in 0.5 and 0.2 T equivalent images,
      respectively. These results demonstrate the feasibility of lung tumor
      autocontouring in low field MR images, and, by extension, intrafractional lung
      tumor tracking with our laboratory's linac-MR system.

PMID- 22380382
TI  - Plate-specific gain map correction for the improvement of detective quantum
      efficiency in computed radiography.
AB  - PURPOSE: The purpose of this work is to improve the noise power spectrum (NPS),
      and thus the detective quantum efficiency (DQE), of computed radiography (CR)
      images by correcting for spatial gain variations specific to individual imaging
      plates. CR devices have not traditionally employed gain-map corrections, unlike
      the case with flat-panel detectors, because of the multiplicity of plates used
      with each reader. The lack of gain-map correction has limited the DQE(f) at
      higher exposures with CR. This current work describes a feasible solution to
      generating plate-specific gain maps. METHODS: Ten high-exposure open field images
      were taken with an RQA5 spectrum, using a sixth generation CR plate suspended in
      air without a cassette. Image values were converted to exposure, the plates
      registered using fiducial dots on the plate, the ten images averaged, and then
      high-pass filtered to remove low frequency contributions from field
      inhomogeneity. A gain-map was then produced by converting all pixel values in the
      average into fractions with mean of one. The resultant gain-map of the plate was
      used to normalize subsequent single images to correct for spatial gain
      fluctuation. To validate performance, the normalized NPS (NNPS) for all images
      was calculated both with and without the gain-map correction. Variations in the
      quality of correction due to exposure levels, beam voltage/spectrum, CR reader
      used, and registration were investigated. RESULTS: The NNPS with plate-specific
      gain-map correction showed improvement over the noncorrected case over the range
      of frequencies from 0.15 to 2.5 mm(-1). At high exposure (40 mR), NNPS was 50%
      90% better with gain-map correction than without. A small further improvement in
      NNPS was seen from carefully registering the gain-map with subsequent images
      using small fiducial dots, because of slight misregistration during scanning.
      Further improvement was seen in the NNPS from scaling the gain map about the mean
      to account for different beam spectra. CONCLUSIONS: This study demonstrates that
      a simple gain-map can be used to correct for the fixed-pattern noise in a given
      plate and thus improve the DQE of CR imaging. Such a method could easily be
      implemented by manufacturers because each plate has a unique bar code and the
      gain-map for all plates associated with a reader could be stored for future
      retrieval. These experiments indicated that an improvement in NPS (and hence,
      DQE) is possible, depending on exposure level, over a wide range of frequencies
      with this technique.

PMID- 22380383
TI  - Experimental assessments of intrafractional prostate motion on sequential and
      simultaneous boost to a dominant intraprostatic lesion.
AB  - PURPOSE: To investigate experimentally the impact of intrafractional prostate
      motion on the delivered dose to a dominant intraprostatic lesion (DIL) using
      volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy
      (IMRT) with sequential and simultaneous boost. METHODS: A series of six IMRT and
      VMAT treatment plans were generated, evaluated, and compared for two patient CT
      scans with dissimilar anatomies. Plans were generated for the prostate with and
      without the DIL. Plans were delivered using a Varian CLINAC and 2D dose
      distributions were measured using mapcheck(TM)-mapphan(TM) system. The effect of
      the prostate intrafractional motion on the delivery of the plans was studied by
      delivering the plans to the mapcheck(TM)-mapphan(TM) system on a programmable
      motion platform. Prostate intrafractional motion was simulated based on six
      different motion patterns from the literature obtained on Calypso system (Calypso
      System, Calypso Medical, Seattle, WA, USA) in a clinical study that provided
      continuous, real-time localization, and monitoring of the prostate. Absolute dose
      differences and Gamma analysis were used to assess the quality of a total of 42
      plans with motion and without motion. RESULTS: Dose escalation to the whole
      prostate from 76 to 86 Gy caused the rectum and bladder to exceed normal tissue
      tolerances in both patients. All the DIL boost plans satisfied the planning
      criteria and delivery quality assurance when motion was not present. For a single
      fraction, the motion pattern with large constant shift caused the largest dose
      delivery discrepancy with mean Gamma value (1.14-1.44) and the lowest plan
      passing percentage (18.9%-35.7%), while the motion pattern with continuous random
      changes during treatment had the least impact on dose delivery with mean Gamma
      value (0.33-0.55) and the highest passing percentage (81.9%-100%) for all the
      investigated plans. For dose escalation to DIL in the presence of intrafractional
      prostate motion, a significant difference was observed between the different
      motion patterns (p < 0.05), but no significant difference in the sensitivity to
      motion between the various plans was observed (p = 0.30). Based on Gamma
      analysis, treatment courses in which 15% of the fractions are dominated by severe
      motion proved to be significantly different from those dominated by random motion
      (p < 0.05). CONCLUSIONS: The impact of intrafractional prostate motion on dose
      delivery is sensitive to different motion patterns but not to different delivery
      techniques. Dose escalation to DIL using either sequential or simultaneous boost
      plans with 7 mm PTV margin is achievable in the presence of intrafractional
      prostate motion, even if the severe motion comprised 8.6% (3 out of the 35)
      treatment fractions.

PMID- 22380384
TI  - Monte Carlo simulation of a novel water-equivalent electronic portal imaging
      device using plastic scintillating fibers.
AB  - PURPOSE: Most electronic portal imaging devices (EPIDs) developed so far use a
      thin Cu plate/phosphor screen to convert x-ray energies into light photons, while
      maintaining a high spatial resolution. This results in a low x-ray absorption and
      thus a low quantum efficiency (QE) of approximately 2-4% for megavoltage (MV) x
      rays. A significant increase of QE is desirable for applications such as MV cone
      beam computed tomography (MV-CBCT). Furthermore, the Cu plate/phosphor screen
      contains high atomic number (high-Z) materials, resulting in an undesirable over
      response to low energy x-rays (due to photoelectric effect) as well as high
      energy x-rays (due to pair production) when used for dosimetric verification. Our
      goal is to develop a new MV x-ray detector that has a high QE and uses low-Z
      materials to overcome the obstacles faced by current MV x-ray imaging
      technologies. METHODS: A new high QE and low-Z EPID is proposed. It consists of a
      matrix of plastic scintillating fibers embedded in a water-equivalent medium and
      coupled to an optically sensitive 2D active matrix flat panel imager (AMFPI) for
      image readout. It differs from the previous approach that uses segmented
      crystalline scintillators made of higher density and higher atomic number
      materials to detect MV x-rays. The plastic scintillating fibers are focused
      toward the x-ray source to avoid image blurring due to oblique incidence of off
      axis x-rays. When MV x-rays interact with the scintillating fibers in the
      detector, scintillation light will be produced. The light photons produced in a
      fiber core and emitted within the acceptance angle of the fiber will be guided
      toward the AMFPI by total internal reflection. A Monte Carlo simulation has been
      used to investigate imaging and dosimetric characteristics of the proposed
      detector under irradiation of MV x-rays. RESULTS: Properties, such as detection
      efficiency, modulation transfer function, detective quantum efficiency (DQE),
      energy dependence of detector response, and water-equivalence of dose response
      have been investigated. It has been found that the zero frequency DQE of the
      proposed detector can be up to 37% at 6 MV. The detector, also, is water
      equivalent with a relatively uniform response to different energy x-rays as
      compared to current EPIDs. CONCLUSIONS: The results of our simulations show that,
      using plastic scintillating fibers, it is possible to construct a water
      equivalent EPID that has a better energy response and a higher detection
      efficiency than current flat panel based EPIDs.

PMID- 22380385
TI  - Dedicated breast CT: radiation dose for circle-plus-line trajectory.
AB  - PURPOSE: Dedicated breast CT prototypes used in clinical investigations utilize
      single circular source trajectory and cone-beam geometry with flat-panel
      detectors that do not satisfy data-sufficiency conditions and could lead to cone
      beam artifacts. Hence, this work investigated the glandular dose characteristics
      of a circle-plus-line trajectory that fulfills data-sufficiency conditions for
      image reconstruction in dedicated breast CT. METHODS: Monte Carlo-based computer
      simulations were performed using the GEANT4 toolkit and was validated with
      previously reported normalized glandular dose coefficients for one prototype
      breast CT system. Upon validation, Monte Carlo simulations were performed to
      determine the normalized glandular dose coefficients as a function of x-ray
      source position along the line scan. The source-to-axis of rotation distance and
      the source-to-detector distance were maintained constant at 65 and 100 cm,
      respectively, in all simulations. The ratio of the normalized glandular dose
      coefficient at each source position along the line scan to that for the circular
      scan, defined as relative normalized glandular dose coefficient (RD(g)N), was
      studied by varying the diameter of the breast at the chest wall, chest-wall to
      nipple distance, skin thickness, x-ray beam energy, and glandular fraction of the
      breast. RESULTS: The RD(g)N metric when stated as a function of source position
      along the line scan, relative to the maximum length of line scan needed for data
      sufficiency, was found to be minimally dependent on breast diameter, chest-wall
      to nipple distance, skin thickness, glandular fraction, and x-ray photon energy.
      This observation facilitates easy estimation of the average glandular dose of the
      line scan. Polynomial fit equations for computing the RD(g)N and hence the
      average glandular dose are provided. CONCLUSIONS: For a breast CT system that
      acquires 300-500 projections over 2pi for the circular scan, the addition of a
      line trajectory with equal source spacing and constant x-ray beam quality (kVp
      and HVL) and mAs matched to the circular scan, will result in less than 0.18%
      increase in average glandular dose to the breast per projection along the line
      scan.

PMID- 22380386
TI  - Automated radiotherapy treatment plan integrity verification.
AB  - PURPOSE: In our clinic, physicists spend from 15 to 60 min to verify the physical
      and dosimetric integrity of radiotherapy plans before presentation to radiation
      oncology physicians for approval. The purpose of this study was to design and
      implement a framework to automate as many elements of this quality control (QC)
      step as possible. METHODS: A comprehensive computer application was developed to
      carry out a majority of these verification tasks in the Philips PINNACLE
      treatment planning system (TPS). This QC tool functions based on both PINNACLE
      scripting elements and PERL sub-routines. The core of this technique is the
      method of dynamic scripting, which involves a PERL programming module that is
      flexible and powerful for treatment plan data handling. Run-time plan data are
      collected, saved into temporary files, and analyzed against standard values and
      predefined logical rules. The results were summarized in a hypertext markup
      language (HTML) report that is displayed to the user. RESULTS: This tool has been
      in clinical use for over a year. The occurrence frequency of technical problems,
      which would cause delays and suboptimal plans, has been reduced since clinical
      implementation. CONCLUSIONS: In addition to drastically reducing the set of human
      driven logical comparisons, this QC tool also accomplished some tasks that are
      otherwise either quite laborious or impractical for humans to verify, e.g.,
      identifying conflicts amongst IMRT optimization objectives.

PMID- 22380387
TI  - Design and characterization of a laterally mounted phased-array transducer breast
      specific MRgHIFU device with integrated 11-channel receiver array.
AB  - PURPOSE: This work presents the design and preliminary evaluation of a new
      laterally mounted phased-array MRI-guided high-intensity focused ultrasound
      (MRgHIFU) system with an integrated 11-channel phased-array radio frequency (RF)
      coil intended for breast cancer treatment. The design goals for the system
      included the ability to treat the majority of tumor locations, to increase the MR
      image's signal-to-noise ratio (SNR) throughout the treatment volume and to
      provide adequate comfort for the patient. METHODS: In order to treat the majority
      of the breast volume, the device was designed such that the treated breast is
      suspended in a 17-cm diameter treatment cylinder. A laterally shooting 1-MHz, 256
      element phased-array ultrasound transducer with flexible positioning is mounted
      outside the treatment cylinder. This configuration achieves a reduced water
      volume to minimize RF coil loading effects, to position the coils closer to the
      breast for increased signal sensitivity, and to reduce the MR image noise
      associated with using water as the coupling fluid. This design uses an 11-channel
      phased-array RF coil that is placed on the outer surface of the cylinder
      surrounding the breast. Mechanical positioning of the transducer and electronic
      steering of the focal spot enable placement of the ultrasound focus at arbitrary
      locations throughout the suspended breast. The treatment platform allows the
      patient to lie prone in a face-down position. The system was tested for comfort
      with 18 normal volunteers and SNR capabilities in one normal volunteer and for
      heating accuracy and stability in homogeneous phantom and inhomogeneous ex vivo
      porcine tissue. RESULTS: There was a 61% increase in mean relative SNR achieved
      in a homogeneous phantom using the 11-channel RF coil when compared to using only
      a single-loop coil around the chest wall. The repeatability of the system's
      energy delivery in a single location was excellent, with less than 3% variability
      between repeated temperature measurements at the same location. The execution of
      a continuously sonicated, predefined 48-point, 8-min trajectory path resulted in
      an ablation volume of 8.17 cm(3), with one standard deviation of 0.35 cm(3)
      between inhomogeneous ex vivo tissue samples. Comfort testing resulted in
      negligible side effects for all volunteers. CONCLUSIONS: The initial results
      suggest that this new device will potentially be suitable for MRgHIFU treatment
      in a wide range of breast sizes and tumor locations.

PMID- 22380388
TI  - A novel easy-to-use phantom for the determination of MTF in SPECT scanners.
AB  - PURPOSE: To evaluate modulation transfer function (MTF) in single photon emission
      computed tomography (SPECT) systems using the line spread function (LSF) method
      and a novel flood source which can be easily fabricated with materials accessible
      in hospital facilities. METHODS: A Tc-99m-based flood source (E(gamma) = 140 keV)
      consisting of a radiopharmaceutical bound to the grains of a radiographic film
      was prepared in laboratory. Various films and radiopharmaceuticals were examined,
      in order to obtain a thin homogenous and reproducible flood source. The source
      showing best uniformity and reproducibility was placed between two PMMA blocks
      and images were obtained by using the brain tomographic acquisition protocol
      (brain) and the myocardial perfusion tomographic acquisition protocol (heart).
      MTF was evaluated by determining the LSF for various reconstruction methods and
      filters. MTF calculation was obtained by the utilization of a custom made
      software in which a method similar to the one proposed by Boone [Med. Phys. 28,
      356-360 (2001)] was implemented. All imaging experiments were performed in a
      Siemens e-Cam gamma-camera. Furthermore, MTF was assessed through the point
      spread function (PSF) following conventional methods. RESULTS: The optimum
      homogeneity was obtained by immersing an Agfa MammoRay HDR Medical x-ray film in
      a solution of dithiothreitol (DTT, 10(-3) M)/Tc-99m(III)-DMSA (DMSA: trivalent
      technetium-99m-dimercapto-succinic acid, 40 mCi/40 ml) for 30 min in the dark.
      These films exhibited better uniformity (CV < 1.9%). Higher MTF values were
      obtained for the brain scan protocol with iterative 3D with eight iterations
      reconstruction method. MTF of the brain protocol was in all cases better than the
      heart protocol. MTFs derived from LSF were more precise compared with those
      obtained from PSF since their reproducibility was better in all cases, providing
      a mean standard deviation of 0.0065, in contrary to the PSF method which gave
      0.0348. CONCLUSIONS: The method presented here is novel and easy to implement,
      requiring materials commonly found in clinical practice. Furthermore, this
      technique which is based on the LSF method reduces measurement noise levels due
      to the larger amount of data averaging than in the conventional PSF method.
      Furthermore, MTF can be assessed easily, in three dimensions (3D), by placing the
      flood source either in sagittal or coronal direction.

PMID- 22380389
TI  - Clinical study of a noninvasive multimodal sono-contrast induced spectroscopy
      system for breast cancer diagnosis.
AB  - PURPOSE: To present a noninvasive multimodal sono-contrast induced spectroscopy
      (SCIS) system for breast cancer detection. METHODS: An IRB approved clinical
      study was carried out to evaluate its diagnostic power. A total of 66 subjects
      were enrolled with informed consent. The study data were grouped into healthy
      breast tissue (26), histologically proven cancer (14), and benign mass (26). The
      diffuse reflectance optical intensity and low intensity focused ultrasound (LIFU)
      signals, as well as ultrasound images, were collected during each study. The
      ratio of optical intensities at wavelengths 685 and 830 nm was analyzed using
      wavelet technique to compare the LIFU effects in cancer and noncancerous tissues.
      The ultrasound images were also processed to obtain tissue texture parameters,
      such as correlation, energy, contrast, homogeneity, etc. Backward stepwise
      regression method was performed to identify the statistically significant factors
      correlating to tissue types (cancer vs benign mass). RESULTS: Comparison of the
      optical signals showed that LIFU induced transitory fluctuation in noncancerous
      tissue, but not in malignant tissue, as quantified by the ratio of mean absolute
      deviation (RMAD) of the high frequency component. Statistical analysis revealed
      that the RMAD ratios were significantly different in tumor vs noncancerous masses
      (p ? 0.01). For tissue texture parameters, energy and correlation were found to
      statistically correlate with the tissue types. A cancer characterization model
      was developed using the weighted factors to differentiate the tumor from the
      benign mass. Trade-off between sensitivity and specificity was obtained by
      varying the threshold value that estimated the upper-bound of the cancer output
      factor, from which the receiver-operating characteristic (ROC) curve was
      generated. The characterization model was optimized using ten modeling datasets
      and verified using another ten validation datasets randomly generated from the
      database. The optimization results show that an AUC of 0.93 can be achieved. With
      threshold 0.3, sensitivity of 96.0%, specificity of 84.1%, and negative
      predictive value (NPV) of 97.3% can be achieved. CONCLUSIONS: The feasibility of
      the multimodal system in characterizing breast cancer vs benign mass is
      established.

PMID- 22380390
TI  - Predicting target vessel location on robot-assisted coronary artery bypass graft
      using CT to ultrasound registration.
AB  - PURPOSE: Although robot-assisted coronary artery bypass grafting (RA-CABG) has
      gained more acceptance worldwide, its success still depends on the surgeon's
      experience and expertise, and the conversion rate to full sternotomy is in the
      order of 15%-25%. One of the reasons for conversion is poor pre-operative
      planning, which is based solely on pre-operative computed tomography (CT) images.
      In this paper, the authors propose a technique to estimate the global peri
      operative displacement of the heart and to predict the intra-operative target
      vessel location, validated via both an in vitro and a clinical study. METHODS: As
      the peri-operative heart migration during RA-CABG has never been reported in the
      literatures, a simple in vitro validation study was conducted using a heart
      phantom. To mimic the clinical workflow, a pre-operative CT as well as peri
      operative ultrasound images at three different stages in the procedure (Stage(0)
      following intubation; Stage(1)-following lung deflation; and Stage(2)-following
      thoracic insufflation) were acquired during the experiment. Following image
      acquisition, a rigid-body registration using iterative closest point algorithm
      with the robust estimator was employed to map the pre-operative stage to each of
      the peri-operative ones, to estimate the heart migration and predict the peri
      operative target vessel location. Moreover, a clinical validation of this
      technique was conducted using offline patient data, where a Monte Carlo
      simulation was used to overcome the limitations arising due to the invisibility
      of the target vessel in the peri-operative ultrasound images. RESULTS: For the in
      vitro study, the computed target registration error (TRE) at Stage(0), Stage(1),
      and Stage(2) was 2.1, 3.3, and 2.6 mm, respectively. According to the offline
      clinical validation study, the maximum TRE at the left anterior descending (LAD)
      coronary artery was 4.1 mm at Stage(0), 5.1 mm at Stage(1), and 3.4 mm at
      Stage(2). CONCLUSIONS: The authors proposed a method to measure and validate peri
      operative shifts of the heart during RA-CABG. In vitro and clinical validation
      studies were conducted and yielded a TRE in the order of 5 mm for all cases. As
      the desired clinical accuracy imposed by this procedure is on the order of one
      intercostal space (10-15 mm), our technique suits the clinical requirements. The
      authors therefore believe this technique has the potential to improve the pre
      operative planning by updating peri-operative migration patterns of the heart
      and, consequently, will lead to reduced conversion to conventional open thoracic
      procedures.

PMID- 22380391
TI  - The dosimetric impact of inversely optimized arc radiotherapy plan modulation for
      real-time dynamic MLC tracking delivery.
AB  - PURPOSE: Real-time dynamic multileaf collimator (MLC) tracking for management of
      intrafraction tumor motion can be challenging for highly modulated beams, as the
      leaves need to travel far to adjust for target motion perpendicular to the leaf
      travel direction. The plan modulation can be reduced by using a leaf position
      constraint (LPC) that reduces the difference in the position of adjacent MLC
      leaves in the plan. The purpose of this study was to investigate the impact of
      the LPC on the quality of inversely optimized arc radiotherapy plans and the
      effect of the MLC motion pattern on the dosimetric accuracy of MLC tracking
      delivery. Specifically, the possibility of predicting the accuracy of MLC
      tracking delivery based on the plan modulation was investigated. METHODS:
      Inversely optimized arc radiotherapy plans were created on CT-data of three lung
      cancer patients. For each case, five plans with a single 358 degrees  arc were
      generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest
      possible LPC), respectively. All the plans had a prescribed dose of 2 Gy * 30,
      used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45 degrees
      or 315 degrees . To quantify the plan modulation, an average adjacent leaf
      distance (ALD) was calculated by averaging the mean adjacent leaf distance for
      each control point. The linear relationship between the plan quality [i.e., the
      calculated dose distributions and the number of monitor units (MU)] and the LPC
      was investigated, and the linear regression coefficient as well as a two tailed
      confidence level of 95% was used in the evaluation. The effect of the plan
      modulation on the performance of MLC tracking was tested by delivering the plans
      to a cylindrical diode array phantom moving with sinusoidal motion in the
      superior-inferior direction with a peak-to-peak displacement of 2 cm and a cycle
      time of 6 s. The delivery was adjusted to the target motion using MLC tracking,
      guided in real-time by an infrared optical system. The dosimetric results were
      evaluated using gamma index evaluation with static target measurements as
      reference. RESULTS: The plan quality parameters did not depend significantly on
      the LPC (p >= 0.066), whereas the ALD depended significantly on the LPC (p <
      0.001). The gamma index failure rate depended significantly on the ALD, weighted
      to the percentage of the beam delivered in each control point of the plan
      (ALD(w)) when MLC tracking was used (p < 0.001), but not for delivery without MLC
      tracking (p >= 0.342). The gamma index failure rate with the criteria of 2% and 2
      mm was decreased from > 33.9% without MLC tracking to <31.4% (LPC 0) and <2.2%
      (LPC 1) with MLC tracking. CONCLUSIONS: The results indicate that the dosimetric
      robustness of MLC tracking delivery of an inversely optimized arc radiotherapy
      plan can be improved by incorporating leaf position constraints in the objective
      function without otherwise affecting the plan quality. The dosimetric robustness
      may be estimated prior to delivery by evaluating the ALD(w) of the plan.

PMID- 22380392
TI  - Reproducibility of registration-based measures of lung tissue expansion.
AB  - PURPOSE: Lung function depends on lung expansion and contraction during the
      respiratory cycle. Respiratory-gated CT imaging and 3D image registration can be
      used to locally estimate lung tissue expansion and contraction (regional lung
      volume change) by computing the determinant of the Jacobian matrix of the image
      registration deformation field. In this study, the authors examine the
      reproducibility of Jacobian-based measures of lung tissue expansion in two repeat
      4DCT acquisitions of mechanically ventilated sheep and free-breathing humans.
      METHODS: 4DCT image data from three white sheep and nine human subjects were used
      for this analysis. In each case, two 4DCT studies were acquired for each subject
      within a short time interval. The animal subjects were anesthetized and
      mechanically ventilated, while the humans were awake and spontaneously breathing
      based on respiratory pacing audio cues. From each 4DCT data set, an image pair
      consisting of a volume reconstructed near end inspiration and a volume
      reconstructed near end exhalation was selected. The end inspiration and end
      exhalation images were registered using a tissue volume preserving deformable
      registration algorithm and the Jacobian of the registration deformation field was
      used to measure regional lung expansion. The Jacobian map from the baseline data
      set was compared to the Jacobian map from the followup data by measuring the
      voxel-by-voxel Jacobian ratio. RESULTS: In the animal subjects, the mean Jacobian
      ratio (baseline scan Jacobian divided by followup scan Jacobian, voxel-by-voxel)
      was 0.9984+/-0.021 (mean +/- standard deviation, averaged over the entire lung
      region). The mean Jacobian ratio was 1.0224+/-0.058 in the human subjects. The
      reproducibility of the Jacobian values was found to be strongly dependent on the
      reproducibility of the subject's respiratory effort and breathing pattern.
      CONCLUSIONS: Lung expansion, a surrogate for lung function, can be assessed using
      two or more respiratory-gated CT image acquisitions. The results show that good
      reproducibility can be obtained in anesthetized, mechanically ventilated animals,
      but variations in respiratory effort and breathing patterns reduce
      reproducibility in spontaneously-breathing humans. The global linear
      normalization can globally compensate for breathing effort differences, but a
      homogeneous scaling does not account for differences in regional lung expansion
      rates. Additional work is needed to develop compensation procedures or
      normalization schemes that can account for local variations in lung expansion
      during respiration.

PMID- 22380393
TI  - Computerized scheme for evaluating mammographic phantom images.
AB  - PURPOSE: The authors developed a computer algorithm to automatically evaluate
      images of the American College of Radiology (ACR) mammography accreditation
      phantom. METHODS: The developed algorithm consist of the edge detection of wax
      insert, nonuniformity correction of background, and correction for magnification
      and also calculate the cross-correlation coefficient by image matching technique.
      The algorithm additionally evaluates target shape for fibers, target contrast for
      speck groups, and target circularity for masses. To obtain an ideal template
      image without noise and spatial resolution loss, the wax insert containing the
      embedded test pattern was extracted from the phantom and radiographed. Two
      template images and ten test phantom images were prepared for this study. The
      results of evaluation using the algorithm outputs were compared with the averaged
      results of observer studies by six skilled observers. RESULTS: In comparing the
      results from the algorithm outputs with the results of observers, the authors
      found that the computer outputs were well correlated with the evaluations by
      observers, and they indicate the quality of the phantom image. The correlation
      coefficients between results of observer studies and two outputs of computer
      algorithm, i.e., the cross-correlation coefficient by template matching and
      indices of target shape for fibers, were 0.89 (95% confidence interval, 0.82
      0.93; hereinafter the same) and 0.85 (0.76-0.91). The correlation coefficients
      between observer's results and two outputs: the cross-correlation coefficient and
      indices of target contrast for speck groups, were 0.83 (0.79-0.86) and 0.85 (0.81
      0.88) and between observer's results and two outputs: the cross-correlation
      coefficient and indices of target circularity for masses, were 0.90 (0.84-0.94)
      and 0.87 (0.77-0.92). CONCLUSIONS: Image evaluation using the ACR phantom is
      indispensable in quality control of a mammography system. The proposed algorithm
      is useful for quality control and image evaluation of mammography units.

PMID- 22380394
TI  - Beam quality conversion factors for parallel-plate ionization chambers in MV
      photon beams.
AB  - PURPOSE: To investigate the behavior of plane-parallel ion chambers in high
      energy photon beams through measurements and Monte Carlo simulations. METHODS:
      Ten plane-parallel ion chamber types were obtained from the major ion chamber
      manufacturers. Absorbed dose-to-water calibration coefficients are measured for
      these chambers and k(Q) factors are determined. In the process, the behaviors of
      the chambers are characterized through measurements of leakage currents, chamber
      settling in cobalt-60, polarity and ion recombination behavior, and long-term
      stability. Monte Carlo calculations of the absorbed dose to the air in the ion
      chamber and absorbed dose to water are obtained to calculate k(Q) factors.
      Systematic uncertainties in Monte Carlo calculated k(Q) factors are investigated
      by varying material properties and chamber dimensions. RESULTS: Chamber behavior
      was variable in MV photon beams, especially with regard to chamber leakage and
      ion recombination. The plane-parallel chambers did not perform as well as
      cylindrical chambers. Significant differences up to 1.5% were observed in
      calibration coefficients after a period of eight months although k(Q) factors
      were consistent on average within 0.17%. Chamber-to-chamber variations in k(Q)
      factors for chambers of the same type were at the 0.2% level. Systematic
      uncertainties in Monte Carlo calculated k(Q) factors ranged between 0.34% and
      0.50% depending on the chamber type. Average percent differences between measured
      and calculated k(Q) factors were - 0.02%, 0.18%, and - 0.16% for 6, 10, and 25 MV
      beams, respectively. CONCLUSIONS: Excellent agreement is observed on average at
      the 0.2% level between measured and Monte Carlo calculated k(Q) factors.
      Measurements indicate that the behavior of these chambers is not adequate for
      their use for reference dosimetry of high-energy photon beams without a more
      extensive QA program than currently used for cylindrical reference-class ion
      chambers.

PMID- 22380395
TI  - Dense GPU-enhanced surface reconstruction from stereo endoscopic images for
      intraoperative registration.
AB  - PURPOSE: In laparoscopic surgery, soft tissue deformations substantially change
      the surgical site, thus impeding the use of preoperative planning during
      intraoperative navigation. Extracting depth information from endoscopic images
      and building a surface model of the surgical field-of-view is one way to
      represent this constantly deforming environment. The information can then be used
      for intraoperative registration. Stereo reconstruction is a typical problem
      within computer vision. However, most of the available methods do not fulfill the
      specific requirements in a minimally invasive setting such as the need of real
      time performance, the problem of view-dependent specular reflections and large
      curved areas with partly homogeneous or periodic textures and occlusions.
      METHODS: In this paper, the authors present an approach toward intraoperative
      surface reconstruction based on stereo endoscopic images. The authors describe
      our answer to this problem through correspondence analysis, disparity correction
      and refinement, 3D reconstruction, point cloud smoothing and meshing. Real-time
      performance is achieved by implementing the algorithms on the gpu. The authors
      also present a new hybrid cpu-gpu algorithm that unifies the advantages of the
      cpu and the gpu version. RESULTS: In a comprehensive evaluation using in vivo
      data, in silico data from the literature and virtual data from a newly developed
      simulation environment, the cpu, the gpu, and the hybrid cpu-gpu versions of the
      surface reconstruction are compared to a cpu and a gpu algorithm from the
      literature. The recommended approach toward intraoperative surface reconstruction
      can be conducted in real-time depending on the image resolution (20 fps for the
      gpu and 14fps for the hybrid cpu-gpu version on resolution of 640 * 480). It is
      robust to homogeneous regions without texture, large image changes, noise or
      errors from camera calibration, and it reconstructs the surface down to sub
      millimeter accuracy. In all the experiments within the simulation environment,
      the mean distance to ground truth data is between 0.05 and 0.6 mm for the hybrid
      cpu-gpu version. The hybrid cpu-gpu algorithm shows a much more superior
      performance than its cpu and gpu counterpart (mean distance reduction 26% and
      45%, respectively, for the experiments in the simulation environment).
      CONCLUSIONS: The recommended approach for surface reconstruction is fast, robust,
      and accurate. It can represent changes in the intraoperative environment and can
      be used to adapt a preoperative model within the surgical site by registration of
      these two models.

PMID- 22380396
TI  - Technical note: suppression of artifacts arising from simultaneous cone-beam
      imaging and RF transponder tracking in prostate radiotherapy.
AB  - PURPOSE: Artifacts in treatment-room cone-beam reconstructions have been observed
      at the authors' center when cone-beam acquisition is simultaneous with radio
      frequency (RF) transponder tracking using the Calypso 4D system (Calypso Medical,
      Seattle, WA). These artifacts manifest as CT-number modulations and increased CT
      noise. The authors present a method for the suppression of the artifacts.
      METHODS: The authors propose a three-stage postprocessing technique that can be
      applied to image volumes previously reconstructed by a cone-beam system. The
      stages are (1) segmentation of voxels into air, soft-tissue, and bone; (2)
      application of a 2D spatial-filter in the axial plane to the soft-tissue voxels;
      and (3) normalization to remove streaking along the axial-direction. The
      algorithm was tested on patient data acquired with Synergy XVI cone-beam CT
      systems (Elekta, Crawley, United Kingdom). RESULTS: The computational demands of
      the suggested correction are small, taking less than 15 s per cone-beam
      reconstruction on a desktop PC. For a moderate loss of spatial-resolution, the
      artifacts are strongly suppressed and low-contrast visibility is improved.
      CONCLUSIONS: The correction technique proposed is fast and effective in removing
      the artifacts caused by simultaneous cone-beam imaging and RF-transponder
      tracking.

PMID- 22380397
TI  - Toward automatic regional analysis of pulmonary function using inspiration and
      expiration thoracic CT.
AB  - PURPOSE: To analyze pulmonary function using a fully automatic technique which
      processes pairs of thoracic CT scans acquired at breath-hold inspiration and
      expiration, respectively. The following research objectives are identified to:
      (a) describe and systematically analyze the processing pipeline and its results;
      (b) verify that the quantitative, regional ventilation measurements acquired
      through CT are meaningful for pulmonary function analysis; (c) identify the most
      effective of the calculated measurements in predicting pulmonary function; and
      (d) demonstrate the potential of the system to deliver clinically important
      information not available through conventional spirometry. METHODS: A pipeline of
      automatic segmentation and registration techniques is presented and demonstrated
      on a database of 216 subjects well distributed over the various stages of COPD
      (chronic obstructive pulmonary disorder). Lungs, fissures, airways, lobes, and
      vessels are automatically segmented in both scans and the expiration scan is
      registered with the inspiration scan using a fully automatic nonrigid
      registration algorithm. Segmentations and registrations are examined and scored
      by expert observers to analyze the accuracy of the automatic methods.
      Quantitative measures representing ventilation are computed at every image voxel
      and analyzed to provide information about pulmonary function, both globally and
      on a regional basis. These CT derived measurements are correlated with results
      from spirometry tests and used as features in a kNN classifier to assign COPD
      global initiative for obstructive lung disease (GOLD) stage. RESULTS: The steps
      of anatomical segmentation (of lungs, lobes, and vessels) and registration in the
      workflow were shown to perform very well on an individual basis. All CT-derived
      measures were found to have good correlation with spirometry results, with
      several having correlation coefficients, r, in the range of 0.85-0.90. The best
      performing kNN classifier succeeded in classifying 67% of subjects into the
      correct COPD GOLD stage, with a further 29% assigned to a class neighboring the
      correct one. CONCLUSIONS: Pulmonary function information can be obtained from
      thoracic CT scans using the automatic pipeline described in this work. This
      preliminary demonstration of the system already highlights a number of points of
      clinical importance such as the fact that an inspiration scan alone is not
      optimal for predicting pulmonary function. It also permits measurement of
      ventilation on a per lobe basis which reveals, for example, that the condition of
      the lower lobes contributes most to the pulmonary function of the subject. It is
      expected that this type of regional analysis will be instrumental in advancing
      the understanding of multiple pulmonary diseases in the future.

PMID- 22380398
TI  - An improved physics-based approach for unfolding megavoltage bremsstrahlung
      spectra using transmission analysis.
AB  - PURPOSE: To develop a physics-based approach to improve the accuracy and
      robustness of the ill-conditioned problem of unfolding megavoltage bremsstrahlung
      spectra from transmission data. METHODS: Spectra are specified using a rigorously
      benchmarked functional form. Since ion chambers are the typical detector used in
      transmission measurements, the energy response of a Farmer chamber is calculated
      using the EGSnrc Monte Carlo code, and the effect of approximating the energy
      response on the accuracy of the unfolded spectra is studied. A proposal is
      introduced to enhance spectral sensitivity by combining transmission data
      measured with multiple detectors of different energy response and by combining
      data from multiple attenuating materials. Monte Carlo methods are developed to
      correct for nonideal exponential attenuation (e.g., scatter effects and secondary
      attenuation). The performance of the proposed methods is evaluated for a diverse
      set of validated clinical spectra (3.5-25 MV) using analytical transmission data
      with simulated experimental noise. RESULTS: The approximations commonly used in
      previous studies for the ion-chamber energy response lead to significant errors
      in the unfolded spectra. Of the configurations studied, the one with best
      spectral sensitivity is to measure four full transmission curves using separate
      low-Z and high-Z attenuators in conjunction with two detectors of different
      energy response (the authors propose a Farmer-type ion chamber, once with a low
      Z, and once with a high-Z buildup cap material), then to feed the data
      simultaneously to the unfolding algorithm. Deviations from ideal exponential
      attenuation are as much as 1.5% for the smallest transmission signals, and the
      proposed methods properly correct for those deviations. The transmission data
      with enhanced spectral sensitivity, combined with the accurate and flexible
      spectral functional form, lead to robust unfolding without requiring a priori
      knowledge of the spectrum. Compared with the commonly-used methods, the accuracy
      is improved for the unfolded spectra and for the unfolded mean incident electron
      kinetic energy by at least factors of three and four, respectively. With
      simulated experimental noise and a lowest transmission of 1%, the unfolded energy
      fluence spectra agree with the original spectra with a normalized root-mean
      square deviation, %Delta(psi), of 2.3%. The unfolded mean incident electron
      kinetic energies agree, on average, with the original values within 1.4%. A
      lowest transmission of only 10% still allows unfolding with %Delta(psi) of 3.3%.
      CONCLUSIONS: In the presence of realistic experimental noise, the proposed
      approach significantly improves the accuracy and robustness of the spectral
      unfolding problem for all therapy and MV imaging beams of clinical interest.

PMID- 22380399
TI  - Response to "comment on 'bridging the gap between IMRT and VMAT: dense angularly
      sampled and sparse intensity modulated radiation therapy'" [Med. Phys. 38, 4912
      4919 (2011)].

PMID- 22380400
TI  - In regards to Kirby et al. "Physics strategies for sparing neural stem cells
      during whole-brain radiation treatments," [Med. Phys. 38, 5338 (2011)].

PMID- 22380404
TI  - Effects of Litchi chinensis fruit isolates on prostaglandin E(2) and nitric oxide
      production in J774 murine macrophage cells.
AB  - BACKGROUND: Litchi chinensis is regarded as one of the 'heating' fruits in China,
      which causes serious inflammation symptoms to people. METHODS: In the current
      study, the effects of isolates of litchi on prostaglandin E(2) (PGE(2)) and
      nitric oxide (NO) production in J774 murine macrophage cells were investigated.
      RESULTS: The AcOEt extract (EAE) of litchi was found effective on stimulating
      PGE(2) production, and three compounds, benzyl alcohol, hydrobenzoin and 5
      hydroxymethyl-2-furfurolaldehyde (5-HMF), were isolated and identified from the
      EAE. Benzyl alcohol caused markedly increase in PGE(2) and NO production,
      compared with lipopolysaccharide (LPS) as positive control, and in a dose
      dependent manner. Hydrobenzoin and 5-HMF were found in litchi for the first time,
      and both of them stimulated PGE(2) and NO production moderately in a dose
      dependent manner. Besides, regulation of cyclooxygenase-2 (COX-2) and inducible
      nitric oxide synthase (iNOS) mRNA expression and NF-kappaB (p50) activation might
      be involved in mechanism of the stimulative process. CONCLUSION: The study
      showed, some short molecular compounds in litchi play inflammatory effects on
      human.

PMID- 22380405
TI  - Outcomes post-discharge from an early intervention in psychosis service.
AB  - AIM: To investigate the effectiveness of an early intervention in psychosis (EIP)
      service on engagement and hospital bed usage, post-discharge. A secondary aim was
      to identify if there was a subgroup of patients with 'poor outcomes'. METHOD: A
      naturalistic study comparing engagement and hospital bed day usage of individuals
      who received treatment from an EIP service (n = 75) with those who presented
      before the service was established (n = 113). RESULTS: The EIP service
      demonstrated better engagement with service users in year 5 (P = 0.001). No
      significant differences were observed on hospital bed day usage. When 'poor
      outcome' cases were removed, a trend towards lower bed usage in EIP services
      emerged (P = 0.139). CONCLUSION: EIP services improve engagement with service
      users. There was not a significant reduction in hospital bed usage. However,
      advantages could be masked by a relatively small number of individuals with 'poor
      outcomes'.

PMID- 22380406
TI  - ZSM-5 zeolite single crystals with b-axis-aligned mesoporous channels as an
      efficient catalyst for conversion of bulky organic molecules.
AB  - The relatively small and sole micropores in zeolite catalysts strongly influence
      the mass transfer and catalytic conversion of bulky molecules. We report here
      aluminosilicate zeolite ZSM-5 single crystals with b-axis-aligned mesopores,
      synthesized using a designed cationicamphiphilic copolymer as a mesoscale
      template. This sample exhibits excellent hydrothermal stability. The orientation
      of the mesopores was confirmed by scanning and transmission electron microscopy.
      More importantly, the b-axis-aligned mesoporous ZSM-5 shows much higher catalytic
      activities for bulky substrate conversion than conventional ZSM-5 and ZSM-5 with
      randomly oriented mesopores. The combination of good hydrothermal stability with
      high activities is important for design of novel zeolite catalysts. The b-axis
      aligned mesoporous ZSM-5 reported here shows great potential for industrial
      applications.

PMID- 22380407
TI  - A study of clinico-pathological parameters and O6-methylguanine DNA
      methyltransferase (MGMT) promoter methylation status in the prognostication of
      gliosarcoma.
AB  - Gliosarcoma is a rare variant of glioblastoma multiforme (GBM) with similar
      clinical presentation and prognosis but a distinct genetic profile. The
      clinicopathological features of 22 cases of gliosarcoma were analyzed with
      respect to age, sex, KPS score, operative diagnosis, extent of resection and
      histopathological subtype (predominantly sarcomatous [PS], predominantly
      gliomatous [PG] or mixed). Twelve cases were PS, six were PG and four were mixed.
      The histological subtype did not correlate with the operative diagnosis; however,
      it did significantly correlate with the extent of resection (P=0.014). In 14
      cases with available survival data it was found that none of the
      clinicopathological parameters significantly correlated with survival (P>0.05).
      Methyl guanine DNA methyl transferase promoter methylation studies were performed
      using methylation-specific PCR in 16 cases which showed a methylation rate of
      31.25% (5/16). The promoter methylation status did not correlate with the
      histological subtype and did not significantly affect survival (P>0.05). Although
      gliosarcomas continue to be treated in the same way as GBM, the role of
      chemotherapy with temozolomide is not clear. This cohort is the largest to date
      to uniformly receive the Stupp's protocol which is currently "standard of care"
      for GBM. A median overall survival of 18.5 months is substantially higher than
      previous studies, suggesting that temozolomide should be included in gliosarcoma
      therapy.

PMID- 22380408
TI  - Nursing research in theory and practice - is implementation the missing link?

PMID- 22380409
TI  - Scholarship reconsidered: implications for reward and recognition of academic
      staff in schools of nursing and beyond.
AB  - AIMS: This paper discusses the issues facing the nursing academic workforce and
      the development of a project at the University of Wollongong in Australia which
      attempts to address this problem. BACKGROUND: The project draws on Boyer's work
      around 'scholarship reconsidered' to enable new ways of thinking about the nature
      of 'research' and how the work of a diversifying workforce can be recognized and
      rewarded within institutions. METHODS: We conducted a series of interviews with
      senior university staff to identify key issues around academic promotion
      processes. Feedback from these interviews, along with extensive internal and
      external consultation and benchmarking, will be used to redraft promotion
      documentation that includes discipline-specific performance expectations.
      RESULTS: Interviews revealed a number of perceived and actual barriers to
      promotion of academic staff who did not conform to a 'traditional' view of
      research expectations. It was widely felt that unspoken expectations about
      research performance were being used to judge applications for promotion, and
      that this disadvantaged people from practice or professional backgrounds, or
      people who had heavy administrative or clinical roles. CONCLUSIONS: Internal
      university processes need to reflect the reality of a diversified workforce.
      Practice and professional disciplines have responsibilities beyond meeting
      traditional research output measurements. More flexible and transparent
      expectation guidelines and career development pathways are needed to build
      holistic schools and faculty and enable maximum staff productivity. IMPLICATIONS
      FOR NURSING MANAGEMENT: By redefining scholarship, schools and faculties are able
      to meet the multiple demands of the government, the institution, individual
      staff, students and the profession. Not everyone can do traditional research all
      the time, and staff involved in other scholarly work should be able to rewarded
      and promoted. By taking the lead in this issue, nursing as a discipline can set
      its own agenda, and pave the way for other disciplines. It can also go a long way
      to solving issues around the dwindling academic workforce.

PMID- 22380410
TI  - Reflect and learn together - when two supervisors interact in the learning
      support process of nurse education.
AB  - AIM: To describe the importance of supervisors working together in supporting the
      learning process of nurse students through reflective caring science supervision.
      BACKGROUND: A supervision model has been developed in order to meet the need for
      interweaving theory and practice. The model is characterized by learning
      reflection in caring science. A unique aspect of the present project was that the
      student groups were led by a teacher and a nurse. METHOD: Data were collected
      through interviews with the supervisors. The analysis was performed with a
      phenomenological approach. RESULTS: The results showed that theory and practice
      can be made more tangible and interwoven by using two supervisors in a dual
      supervision. The essential structure is built on the constituents 'Reflection as
      Learning Support', 'Interweaving Caring Science with the Patient's Narrative',
      'The Student as a Learning Subject' and 'The Learning Environment of
      Supervision'. CONCLUSION: The study concludes that supervision in pairs provides
      unique possibilities for interweaving and developing theory and practice.
      IMPLICATIONS FOR NURSING MANAGEMENT: The supervision model offers unique
      opportunities for cooperation, for the development of theory and practice and for
      the development of the professional roll of nurses and teachers.

PMID- 22380411
TI  - Nursing leadership practices as perceived by Finnish nursing staff: high ethics,
      less feedback and rewards.
AB  - AIMS: The purpose was to examine the perceptions of Finnish nursing staff of
      their nursing leadership and how nurses' background variables are associated with
      their perceptions. BACKGROUND: Nursing leadership practices and behaviours
      influence nursing staff work performances. In Finland, studies examining
      leadership practices from the perspective of nursing staff are limited. METHODS:
      This quantitative, cross-sectional study involved four hospitals in Eastern
      Finland. A total of 1497 nursing staff completed the structured electronic
      questionnaire. RESULTS: In general, seven out of 10 nursing staff held positive
      perceptions about leadership ethics and their professional development. Over one
      third of nursing staff were dissatisfied with the nursing process and with their
      feedback and rewards, while only four out of 10 evaluated their nursing director
      either in a positive or negative way. There were no significant differences
      regarding their perceptions when different background variables were taken into
      account. CONCLUSION: Nursing leadership needs the opinion of nursing staff in
      order to help formulate a favourable work environment where they can utilize
      their full potential and improve nursing care. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nursing staff expect feedback and rewards, involvement in the
      decision making process, and clear vision from nurse leaders.

PMID- 22380412
TI  - Nurses' patient-education work: conditional factors - an integrative review.
AB  - AIM: The aim of this review was to identify conditional factors for nurses'
      patient-education work and to identify foundational aspects of significance when
      designing studies on this patient-education work. BACKGROUND: A few reviews of
      nurses patient education work exist, published up to 30 years ago, spawning
      interest in performing a review of more recent studies. EVALUATION: A search of
      CINAHL, MEDLINE and ERIC was made for articles dating from 1998 to 2011. Thirty
      two articles were selected and an integrative review was performed. KEY ISSUES:
      Conditional factors were identified and beliefs and knowledge, environment,
      organization, interdisciplinary cooperation, collegial teamwork and patient
      education activities. A model was developed to describe foundational aspects of
      significance when designing studies. CONCLUSIONS: The conditional factors are to
      be seen as either enabling or hindering the accomplishment of evidence-based
      patient education and the level of person centredness, patient safe care and
      ethics - something that has to be considered when designing studies. IMPLICATIONS
      FOR NURSING MANAGEMENT: More detailed studies are required to clarify the nature
      of patient education work and to create realistic conditions that enable the role
      to be fulfilled in everyday work. Such knowledge is of significance for nursing
      management in developing supportive activities for nurses.

PMID- 22380413
TI  - Nursing leadership in a chronic pain management group approach.
AB  - AIM: To explore and debate nursing leadership and challenges on organizational
      and group levels when conducting rehabilitation groups for people suffering from
      chronic pain. BACKGROUND: Group approaches based on cognitive behavioural therapy
      are generally described as effective. Leadership in group approaches offered to
      people suffering from chronic pain is a great challenge for nurses on an
      organizational as well as a group level. METHODS: One overall leader and nine
      group leaders conducting 13 groups constituted the sample. Qualitative content
      analysis was used by identifying categories, subthemes and themes. RESULTS: The
      results from the content analysis revealed one main theme ('Complexity in nursing
      leadership') and three subthemes ('Challenges in leadership on organizational
      level', 'Challenges in leadership on teamwork level' and 'Challenges in
      leadership on group level'. CONCLUSIONS: The results show how important it is to
      have firm overall leadership and trained group leaders with a common purpose,
      interdependent roles and complementary skills, who are thus well prepared to
      prevent or deal with challenging group processes. IMPLICATIONS FOR NURSING
      MANAGEMENT: The leaders of both levels, which are highly interrelated, should
      have a current theoretical understanding of pain theory, group leadership skills
      and a cognitive behavioural approach.

PMID- 22380414
TI  - Quality registry, a tool for patient advantages - from a preventive caring
      perspective.
AB  - AIM: The aim of this study was to describe nurses' experiences of a recently
      implemented quality register, Senior Alert, at two hospitals in Sweden.
      BACKGROUND: In Sweden, in recent decades, a system of national quality registries
      has been established in health and medical services for better outcomes for
      patients, professional development and a better functioning system. Senior Alert
      (SA) is one quality registry, aimed at preventing malnutrition, pressure ulcers
      and falls in elderly care. METHODS: The study comprised a total of eight
      interviews with nurses working with SA at the ward level. The interviews were
      analysed using manifest qualitative content analysis. Respect for the individuals
      was a main concern in the study. All persons who were asked to participate in the
      study consented to do so. RESULTS: One category 'Patient Advantages' and three
      subcategories 'Conscious Persevering', 'Supporting Structure' and 'Committed
      Leadership' were identified to describe staff experiences of implementing SA.
      CONCLUSIONS: Implementation processes need to be sustainable at both staff and
      managerial levels. A key factor in implementing and using a quality registry in
      prevention care could be described as keeping the flame burning. However, further
      research is needed on how patient advantages could be developed using other
      quality registries in order to improve care from a patient perspective.
      IMPLICATIONS FOR NURSING MANAGEMENT: The results of this study could help other
      organizations implement quality registries or other change processes, for example
      new guidelines and treatment. Strategies concerning organizational structure and
      committed leadership could increase the usefulness of knowledge systems on all
      levels, which could enable continuous learning and quality improvement in health
      care.

PMID- 22380415
TI  - A quality registers impact on community nurses' in end-of-life care - a grounded
      theory study.
AB  - AIM: The aim of the study was to identify the impact of a quality register in end
      of-life-care, from community nurses' perspective. BACKGROUND: There is a lack of
      knowledge about the impact of such a register in end-of-life care. METHOD: Data
      were collected by means of focus group interviews with a total of 12 nurses, from
      two communities in the western part of Sweden. Data analysis was based on
      grounded theory. RESULT: Feedback is the core category that influences all other
      processes. Two main categories emerged: 'Becoming aware of' and 'Acting
      accordingly'. These influenced the nurses and led to improved quality of care.
      CONCLUSION: A quality register gives the users (nurses) feedback on the care
      provided, which starts a process of change. IMPLICATIONS FOR NURSING MANAGEMENT:
      The value of working with a quality register as a feedback system can be
      applicable to all professions working with quality assurance. The experiences
      will increase the motivation and understanding the value of using quality
      registers as a tool for enhanced quality. Further, nurse managers can use such a
      register as a feedback system, not only as a motivating tool when implementing a
      quality register, but in the evaluation of its outcomes.

PMID- 22380416
TI  - Research supervision: supervisory style, research-related tasks, importance and
      quality - part 1.
AB  - AIM: To examine postgraduate students' and academic nurse supervisors' views of
      research supervision by focusing on four major issues; supervisory style,
      research-related tasks as well as the importance and quality of research
      supervision. BACKGROUND: Research supervision is central to the higher education
      programme and of particular relevance for scientific development of nursing
      leadership in order to improve health care. METHODS: A descriptive-correlational
      design with descriptive and interferential statistics was used. RESULTS: Problem
      solving, research preparation, communication and interaction appear to be key
      aspects of supervisory style. The research-related tasks of research supervision
      comprised monitoring the research process, providing encouragement and critical
      comments on drafts as well as fostering an academic role. The perception of the
      atmosphere of the session was good and the supervisors' feedback on the text was
      deemed well-prepared and constructive. Overall satisfaction with the quality of
      the academic leadership was high. CONCLUSION: Research supervision is a mutual,
      interactive process aimed at improving the supervisor's ability to be sensitive
      to the students' competence and limitations. IMPLICATIONS FOR NURSING LEADERSHIP:
      Academic leaders have a wide range of roles, research activities and serve as
      role models within their professions. Research supervision needs to be valued in
      order to promote closer and more collaborative research between clinical practice
      and academia.

PMID- 22380417
TI  - Research awareness: managerial challenges for nurses in the Republic of Ireland.
AB  - BACKGROUND: In spite of the growing body of literature, the reality of getting
      research into practice remains problematic. OBJECTIVE: The present study aimed to
      establish contemporary levels of research awareness among nurses in Ireland.
      POPULATION, SAMPLE, SETTING: A random sample of 234 registered nurses (RNs).
      METHODS: A self-report survey Research Awareness Questionnaire (RAQ) was used to
      collect data in March 2005. RESULTS: Most agreed (92%) that research can improve
      patient care and 93% agreed that it is the way forward to change clinical
      practice. Most nurses' perceived research as being integral to their role.
      However, 71% of the nurses within the present study indicated that they had
      insufficient support and encouragement from peers and professionals. Similarly,
      69.2% indicated insufficient support from management. CONCLUSIONS: Consistent
      with other countries, nurses in Ireland have a positive attitude towards evidence
      based nursing but face many obstacles which include a lack of time, support,
      knowledge and confidence. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers
      have a vital role in the use and dissemination of research among staff. It is
      imperative that nurse managers have clinical expertise, research awareness
      training, and awareness to promote research-based practice and attempt to provide
      positive role modelling in addition to protected time for research efforts.

PMID- 22380418
TI  - First-line nurse leaders' health-care change management initiatives.
AB  - AIM: To examine nurse leaders' change management projects within British
      Columbia, Canada. BACKGROUND: British Columbia Nursing Leadership Institute 2007
      10 attendees worked on year-long change management initiatives/projects of
      importance to their respective health-care institutions. Most leaders were in
      first-line positions with <3 years' experience. METHOD: Consenting leaders'
      project reports (N = 133) were content analysed for specific themes: types of
      projects; scope of projects (e.g. unit or local level, departmental,
      institutional); influence targets or key stakeholder groups targeted by the
      projects; leadership successes and challenges. RESULTS: Of study participants,
      77% successfully completed their projects. Staff tool and resource development
      and existing services improvement were major project types. Care delivery teams
      were the major influence targets. Only 25% of projects were at the unit level.
      Many projects had broader scopes, such as institutional levels. Participants
      cited multiple leadership successes, including enhanced leadership styles and
      organizational skills. CONCLUSION: First-line nurse leaders were able to
      successfully manage projects beyond their traditional scope of responsibilities.
      The majority of projects dealt with staff needs and healthcare restructuring
      initiatives. IMPLICATIONS FOR NURSING MANAGEMENT: Constant change is a global
      reality. Change management, a universal competency, must be included in
      leadership development programmes.

PMID- 22380419
TI  - Registered nurse job satisfaction and satisfaction with the professional practice
      model.
AB  - AIMS: This paper describes the initial assessment of job satisfaction and
      satisfaction with the professional practice environment of registered nurses
      working on units where a professional practice model was implemented and the
      relationship between these two variables. BACKGROUND: The nursing shortage has
      been linked to overall job satisfaction and specifically to nurses' satisfaction
      with the professional practice environment. Initiatives to increase retention and
      recruitment and decrease turnover have been linked to work satisfaction among
      nurses. METHODS: A descriptive, cross-sectional design was used with participants
      (N = 101) from four patient care units; this represented a 55% response rate.
      RESULTS: The nurses were moderately satisfied with the professional practice
      environment but had overall low job satisfaction. There was a significant
      negative relationship between overall work satisfaction and satisfaction with the
      professional practice environment (P < 0.0001). CONCLUSIONS: The introduction of
      the professional practice model may have raised awareness of the components of
      job satisfaction that were not being met. Thus, the nurses may have become more
      knowledgeable about the potential needs in these areas. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse managers and leaders must recognize that job satisfaction
      consists of many dimensions, and each of these dimensions is important to nurse
      retention. Implementation of a professional practice model may heighten awareness
      of the missing components within a practice environment and lead to decreased
      overall satisfaction. A broader understanding of characteristics associated with
      increased satisfaction may aid in development of organizational change necessary
      to retain and attract nurses.

PMID- 22380420
TI  - Patient experiences of uncertainty - a synthesis to guide nursing practice and
      research.
AB  - AIM: The aim of this study was to provide a synthesis of patients' experiences of
      uncertainty in illness and the interventions outlined, based on qualitative
      research. BACKGROUND: There is a need to explore various patient experiences from
      a nursing perspective in order to achieve evidence-based practice and improve the
      quality of care. Uncertainty in illness is a dynamic experience - a stressor with
      a major impact on patients' illnesses. METHODS: A literature search performed on
      PubMed and Cinahl yielded 15 qualitative studies that met the inclusion criteria
      and which were analysed and interpreted. RESULTS: Experienced uncertainty was one
      of two main areas comprising three themes: explaining, feeling and facing
      uncertainty. The second main area was suggested intervention strategies
      consisting of three themes: organizing the patient trajectory throughout the
      health-care system, supporting patients through relationships and providing
      knowledge through clear and accurate communication. CONCLUSION: Providing
      insight, confidence and supporting the patients' feeling of control are of
      importance for health-care professionals. IMPLICATIONS FOR NURSING MANAGEMENT:
      Structured organization of the trajectory system should be followed up, while
      outcome measures (patient satisfaction), education and training programmes for
      patients and families after discharge to improve coping strategies and reduce
      uncertainty should be developed. Nurse leaders should work towards the
      establishment of clinical academic nursing positions to integrate knowledge,
      skills, experiences and research into everyday routines.

PMID- 22380421
TI  - Suffering and suffering with the other - the perspective of perioperative nurse
      leaders.
AB  - AIM: To capture and interpret meanings of suffering from the perspective of
      perioperative nurse leaders. BACKGROUND: There are few studies focusing on
      suffering and the meaning of being a nurse leader in a perioperative context.
      METHOD: Hermeneutic interpretation of interviews with nurse leaders. RESULTS: A
      main theme of suffering emerged as learning and non-learning. Suffering as
      learning comprised 'struggling to come to terms with being misunderstood',
      'struggling to wait patiently to be allowed to help', 'struggling to manage daily
      tasks' and 'struggling to be worthy of the trust of superiors'. Suffering as non
      learning comprised 'feeling alone when in charge', 'feeling guilty about not
      managing daily tasks', 'feeling mistrusted by superiors', 'feeling unfairly
      criticized', 'feeling humiliated owing to loss of responsibilities' and 'feeling
      unable to help'. CONCLUSION: Suffering is good when the mission of caring is
      mastered and the nurse leader feels recognized as unique and trustable, leading
      to his or her sense of dignity being preserved. Suffering is evil when the
      mission of caring is threatened, when questioned and not considered a unique and
      trustable person, leading to loss of dignity. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse leaders' suffering needs to be acknowledged and a caring
      culture that permeates the entire organization should be developed.

PMID- 22380422
TI  - Diversity and challenges in the management of maternity care for migrant women.
AB  - AIM: To illuminate midwives' and public health nurses' perceptions of managing
      and supporting prenatal and postnatal migrant women in Norway. BACKGROUND:
      Migrant women are affected by social inequalities and likely to have had
      experiences during and after the migration process that could influence their
      physical, mental and social well-being. METHODS: Multistage focus group
      interviews were conducted and data were analysed in accordance to conventional
      interpretative qualitative content analysis. RESULTS: The overarching theme
      'Managing and supporting educational, relational and cultural diversity in
      maternity care' was characterized by two themes 'Health challenges' and 'Cultural
      challenges'. Each theme contained several subthemes. The interviews revealed that
      Norwegian maternity care is not adjusted to migrant women's needs. The management
      is the same for everybody who avails of the service. CONCLUSION: The Norwegian
      model for managing cultural diversity in maternity care needs to be developed.
      Capacity building and a closer cooperation between maternity care services is
      necessary. IMPLICATIONS FOR MIDWIVES AND NURSING MANAGEMENT: Maternity care
      requires reflection at several levels to reduce disparities in individual health.
      In order to ensure continuity and a trusting relationship, it is necessary to
      organize leadership and adopt flexible models that support migrant women's
      health.

PMID- 22380423
TI  - Letter to the editor: responding to civilizing the 'barbarian'.

PMID- 22380424
TI  - NMR study of cation dynamics in three crystalline states of 1-butyl-3
      methylimidazolium hexafluorophosphate exhibiting crystal polymorphism.
AB  - We investigate the cation rotational dynamics of a room temperature ionic liquid
      (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate ([C(4)mim]PF(6)) in its
      three crystalline states by (1)H NMR spectroscopy. Spin-lattice and spin-spin
      relaxation time (T(1) and T(2), respectively) measurements as a function of
      temperature confirm the presence of three polymorphic crystals of [C(4)mim]PF(6):
      crystals alpha, beta, and gamma, which we previously discovered using Raman
      spectroscopy and calorimetry. Second moment calculations of (1)H NMR spectra
      reveal that certain segmental motions of the butyl group in addition to the rapid
      rotation of the two methyl groups in the cation occur in all the crystals. The
      trend in the mobility of the segmental motions is gamma < beta <= alpha, which is
      consistent with the strength of cation-anion interactions (or crystal packing
      density) estimated from high-frequency Raman scattering experiments. T(1)
      measurements demonstrate two types of rotational motions on the nanosecond time
      scale in all three crystals: fast and slow motions. The three crystals have
      similar activation energies of 12.5-15.1 kJ mol(-1) for the fast motion, which is
      assigned to the rotation of the methyl group at the terminal of the butyl group.
      These observed activation energies were consistent with that estimated by quantum
      chemical calculations in the gas phase (11.9 kJ mol(-1)). In contrast, the slow
      motions of crystals alpha and gamma are attributed to different segmental motions
      of the butyl group and that of crystal beta to either a little segmental motion
      or a certain PF(6)(-) rotational motion. These nanosecond rotational motions
      obtained from the T(1) measurements do not appear to be affected by crystal
      packing density because local interactions in the crystalline state rather than
      packing density govern such nanosecond motions. With respect to the segmental
      motions, the mobility is likely to change significantly with the conformation of
      the butyl group. On the basis of these findings, crystal gamma, which is the only
      crystalline phase previously determined using single-crystal X-ray diffraction,
      is considered to be the most stable phase because of the slowest segmental
      motions and the strongest cation-anion interactions.

PMID- 22380425
TI  - Argatroban therapy for heparin-induced thrombocytopenia during pregnancy in a
      woman with hereditary antithrombin deficiency.
AB  - A 33-year-old woman developed deep venous thrombosis at 7 gestational weeks (GW).
      Heparin-induced thrombocytopenia was evident at 9 GW during unfractionated
      heparin infusion. Immediately, anticoagulation therapies together with
      antithrombin (AT) infusion were commenced with the use of argatroban from 9 GW,
      and fondaparinux was substituted for argatroban after 24 GW. The patient had
      hereditary AT deficiency type I determined by laboratory findings and results of
      genomic DNA analysis. The pregnancy ended in full-term vaginal delivery of a
      healthy male without adverse effects of the anticoagulation therapies. This was
      the first report of a pregnant woman who developed heparin-induced
      thrombocytopenia caused by heparin therapy for deep venous thrombosis due to AT
      deficiency.

PMID- 22380426
TI  - Synthesis and evaluation of substituted diphenyl-1,3,4-oxadiazole derivatives for
      central nervous system depressant activity.
AB  - BACKGROUND: Substituted 1,3,4-oxadiazoles are of considerable pharmaceutical
      interest. 2,5-Substituted diphenyl-1,3,4-oxadiazoles are associated with diverse
      biological activities by the virtue of -N = C-O- grouping. In the view of wide
      range of biological properties associated with 1,3,4-oxadiazole, we have
      synthesized substituted derivatives of 1,3,4-oxadiazole (XIII-XXII), a versatile
      hydrophobic molecule possessing preliminary CNS properties, with the hope to
      potentiate the biological activities with lesser or limited amount of toxicities.
      METHOD: The synthesis was based on ester substitution of substituted
      benzohydrazide in presence of hydrazine hydrate followed by cyclization in
      presence of phosphorus oxychloride. All the synthesized compounds were evaluated
      for their potential CNS depressant activities. Statistical analysis of the
      anticonvulsant, antidepressant, and antianxiety activity of the synthesized
      compounds on animals was evaluated using one-way analysis of variance (ANOVA).
      RESULTS: Two compounds 5-(4-nitrophenyl)-2-(4-chlorophenyl)-1,3,4-oxadiazole
      (XIV) and 5-(4-nitrophenyl)-2-(4-nitrophenyl)-1,3,4-oxadiazole (XV) were found to
      be the most promising compounds of the series in antidepressant, anticonvulsant
      and antianxiety activity with no neurotoxicity when compared with standard.
      CONCLUSIONS: Among the synthesized compounds, it was found that incorporation of
      electron withdrawing group at C2 and C5 position of the oxadiazole ring led to
      high degree of pharmacological activity. Thus compounds 5-(4-nitrophenyl)-2-(4
      chlorophenyl)-1,3,4-oxadiazole (XIV) and 5-(4-nitrophenyl)-2-(4-nitrophenyl)
      1,3,4-oxadiazole (XV) showed excellent CNS depressant activities. The result of
      the present investigation may encourage us to develop and/or improve similar
      other related compounds and it may be assumed that further modifications may
      produce compounds of better activity with lesser side effects.

PMID- 22380427
TI  - How evolution generates complexity without design: language as an instructional
      metaphor.
AB  - One of the major stumbling blocks to understanding evolution is the difficulty in
      reconciling the emergence of complexity with the apparently undirected forces
      that drive evolutionary processes. This difficulty was originally framed as the
      "Watch and Watchmaker" argument and more recently revived by proponents of
      "intelligent design." Undergraduates in particular often attribute purpose and
      forethought as the driving force behind biological phenomena, and have difficulty
      understanding evolutionary processes. To demonstrate that complexity can arise
      solely through mutations that fix in populations via natural selection or drift,
      we can use analogies where processes can be observed across short time frames and
      where the key data are accessible to those without specialized biological
      knowledge. The evolution of language provides such an example. Processes of
      natural selection, mutation, genetic drift, acquisition of new functions,
      punctuated equilibria, and lateral gene transfer can be illustrated using
      examples of changing spellings, neologism, and acquisition of words from other
      languages. The examples presented in this article are readily accessible, and
      demonstrate to students that languages have dynamically increased in complexity,
      simply driven by the usage patterns of their speakers.

PMID- 22380428
TI  - Group-size diversity in public goods games.
AB  - Public goods games are models of social dilemmas where cooperators pay a cost for
      the production of a public good while defectors free ride on the contributions of
      cooperators. In the traditional framework of evolutionary game theory, the
      payoffs of cooperators and defectors result from interactions in groups formed by
      binomial sampling from an infinite population. Despite empirical evidence showing
      that group-size distributions in nature are highly heterogeneous, most models of
      social evolution assume that the group size is constant. In this article, I
      remove this assumption and explore the effects of having random group sizes on
      the evolutionary dynamics of public goods games. By a straightforward application
      of Jensen's inequality, I show that the outcome of general nonlinear public goods
      games depends not only on the average group size but also on the variance of the
      group-size distribution. This general result is illustrated with two nonlinear
      public goods games (the public goods game with discounting or synergy and the N
      person volunteer's dilemma) and three different group-size distributions
      (Poisson, geometric, and Waring). The results suggest that failing to acknowledge
      the natural variation of group sizes can lead to an underestimation of the actual
      level of cooperation exhibited in evolving populations.

PMID- 22380429
TI  - Survival of the weakest in N-person duels and the maintenance of variation under
      constant selection.
AB  - The persistence of extensive variation in nature seems to stand against the most
      general principle of evolution by natural selection: in antagonistic
      interactions, the stronger type is expected to replace the weaker. Game theory
      shows that, however, in contrast to this intuitive expectation for interactions
      between two players, strategic considerations on fitness maximization in repeated
      pairwise interactions between three players (truels) or more (N-person duels)
      lead to what can be dubbed "survival of the weakest": the weakest individual can
      have the highest fitness. A paradox arises: competitive skills cannot be improved
      by natural selection, unless we assume mutations with strong effects or unless we
      assume that interactions are exclusively between two individuals. The paradox
      disappears, however, with more realistic assumptions (a mixture of duels and
      truels; the attacked individual backfires; the contest can end without a winner;
      defensive and offensive skills are correlated; players not directly involved in
      the contest suffer collateral damage). An unexpected new result emerges: the
      weaker types can persist in a population in the absence of recurrent mutations,
      migration, and fluctuating selection. Game theory and the analysis of N-person
      duels, therefore, help understand one of the most enduring puzzles in
      evolutionary biology: the maintenance of variation under constant selection.

PMID- 22380430
TI  - The evolution of generalized reciprocity on social interaction networks.
AB  - Generalized reciprocity (help anyone, if helped by someone) is a minimal strategy
      capable of supporting cooperation between unrelated individuals. Its simplicity
      makes it an attractive model to explain the evolution of reciprocal altruism in
      animals that lack the information or cognitive skills needed for other types of
      reciprocity. Yet, generalized reciprocity is anonymous and thus defenseless
      against exploitation by defectors. Recognizing that animals hardly ever interact
      randomly, we investigate whether social network structure can mitigate this
      vulnerability. Our results show that heterogeneous interaction patterns strongly
      support the evolution of generalized reciprocity. The future probability of being
      rewarded for an altruistic act is inversely proportional to the average
      connectivity of the social network when cooperators are rare. Accordingly, sparse
      networks are conducive to the invasion of reciprocal altruism. Moreover, the
      evolutionary stability of cooperation is enhanced by a modular network structure.
      Communities of reciprocal altruists are protected against exploitation, because
      modularity increases the mean access time, that is, the average number of steps
      that it takes for a random walk on the network to reach a defector. Sparseness
      and community structure are characteristic properties of vertebrate social
      interaction patterns, as illustrated by network data from natural populations
      ranging from fish to primates.

PMID- 22380431
TI  - Antagonistic responses to natural and sexual selection and the sex-specific
      evolution of cuticular hydrocarbons in Drosophila simulans.
AB  - Natural and sexual selection are classically thought to oppose one another, and
      although there is evidence for this, direct experimental demonstrations of this
      antagonism are largely lacking. Here, we assessed the effects of sexual and
      natural selection on the evolution of cuticular hydrocarbons (CHCs), a character
      subject to both modes of selection, in Drosophila simulans. Natural selection and
      sexual selection were manipulated in a fully factorial design, and after 27
      generations of experimental evolution, the responses of male and female CHCs were
      assessed. The effects of natural and sexual selection differed greatly across the
      sexes. The responses of female CHCs were generally small, but CHCs evolved
      predominantly in the direction of natural selection. For males, profiles evolved
      via sexual and natural selection, as well as through the interaction between the
      two, with some male CHC components only evolving in the direction of natural
      selection when sexual selection was relaxed. These results indicate sex-specific
      responses to selection, and that sexual and natural selection act
      antagonistically for at least some combinations of CHCs.

PMID- 22380432
TI  - Maintenance of a male-killing Wolbachia in Drosophila innubila by male-killing
      dependent and male-killing independent mechanisms.
AB  - Many maternally inherited endosymbionts manipulate their host's reproduction in
      various ways to enhance their own fitness. One such mechanism is male killing
      (MK), in which sons of infected mothers are killed by the endosymbiont during
      development. Several hypotheses have been proposed to explain the advantages of
      MK, including resource reallocation from sons to daughters of infected females,
      avoidance of inbreeding by infected females, and, if transmission is not purely
      maternal, the facilitation of horizontal transmission to uninfected females. We
      tested these hypotheses in Drosophila innubila, a mycophagous species infected
      with MK Wolbachia. There was no evidence of horizontal transmission in the wild
      and no evidence Wolbachia reduced levels of inbreeding. Resource reallocation
      does appear to be operative, as Wolbachia-infected females are slightly larger,
      on average, than uninfected females, although the selective advantage of larger
      size is insufficient to account for the frequency of infection in natural
      populations. Wolbachia-infected females from the wild-although not those from the
      laboratory-were more fecund than uninfected females. Experimental studies
      revealed that Wolbachia can boost the fecundity of nutrient-deprived flies and
      reduce the adverse effect of RNA virus infection. Thus, this MK endosymbiont can
      provide direct, MK-independent fitness benefits to infected female hosts in
      addition to possible benefits mediated via MK.

PMID- 22380433
TI  - Strong asymmetry in the relative strengths of prezygotic and postzygotic barriers
      between two damselfly sister species.
AB  - One of the longest debates in biology has been over the relative importance of
      different isolating barriers in speciation. However, for most species, there are
      few data evaluating their relative contributions and we can only speculate on the
      general roles of pre- and postzygotic isolation. Here, we quantify the absolute
      and cumulative contribution of 19 potential reproductive barriers between two
      sympatric damselfly sister species, Ischnura elegans and I. graellsii, including
      both premating (habitat, temporal, sexual and mechanical isolation) and
      postmating barriers (prezygotic: sperm insemination success and removal rate,
      oviposition success, fertility, fecundity; postzygotic: hybrid viability, hybrid
      sterility and hybrid breakdown). In sympatry, total reproductive isolation
      between I. elegans females and I. graellsii males was 95.2%, owing mostly to a
      premating mechanical incompatibility (93.4%), whereas other barriers were of
      little importance. Isolation between I. graellsii females and I. elegans males
      was also nearly complete (95.8%), which was caused by the cumulative action of
      multiple prezygotic (n= 4, 75.4%) and postzygotic postmating barriers (n= 5,
      7.4%). Our results suggest that premating barriers are key factors in preventing
      gene flow between species, and that the relative strengths of premating barriers
      is highly asymmetrical between the reciprocal crosses.

PMID- 22380434
TI  - Eutrophication and predation risk interact to affect sexual trait expression and
      mating success.
AB  - Sexual traits are especially sensitive to low food resources. Other environmental
      parameters (e.g., predation) should also affect sexual trait expression by
      favoring investment in viability traits rather than sexual traits. We know
      surprisingly little about how predators alter investment in sexual traits, or how
      predator and resource environments interact to affect sexual trait investment. We
      explored how increasing phosphorous (P) availability, at a level mimicking
      cultural eutrophication, affects the development of sexual, nonsexual, and
      viability traits of amphipods in the presence and absence of predators. Sexual
      traits and growth were hypersensitive to low P compared to nonsexual traits.
      However, a key sexual trait responded to low P only when predator cues were
      absent. Furthermore, investment trade-offs between sexual traits and growth only
      occurred when P was low. The phenotypic changes caused by predator cues and
      increased P availability resulted in higher male mating success. Thus,
      eutrophication not only affects sexual trait expression but also masks the trade
      off between traits with similar P demand. Sensitivity of sexually selected traits
      to changes in P, combined with the important roles these traits play in
      determining fitness and driving speciation, suggests that human-induced
      environmental change can greatly alter the evolutionary trajectories of
      populations.

PMID- 22380435
TI  - Contrasting patterns of diversity and population differentiation at the innate
      immunity gene toll-like receptor 2 (TLR2) in two sympatric rodent species.
AB  - Comparing patterns of diversity and divergence between populations at immune
      genes and neutral markers can give insights into the nature and geographic scale
      of parasite-mediated selection. To date, studies investigating such patterns of
      selection in vertebrates have primarily focused on the acquired branch of the
      immune system, whereas it remains largely unknown how parasite-mediated selection
      shapes innate immune genes both within and across vertebrate populations. Here,
      we present a study on the diversity and population differentiation at the innate
      immune gene Toll-like receptor 2 (TLR2) across nine populations of yellow-necked
      mice (Apodemus flavicollis) and bank voles (Myodes glareolus) in southern Sweden.
      In yellow-necked mice, TLR2 diversity was very low, as was TLR2 population
      differentiation compared to neutral loci. In contrast, several TLR2 haplotypes co
      occurred at intermediate frequencies within and across bank vole populations, and
      pronounced isolation by distance between populations was observed. The diversity
      and differentiation at neutral loci was similar in the two species. These results
      indicate that parasite-mediated selection has been acting in dramatically
      different ways on a given immune gene in ecologically similar and sympatric
      species. Furthermore, the finding of TLR2 population differentiation at a small
      geographical scale in bank voles highlights that vertebrate innate immune defense
      may be evolutionarily more dynamic than has previously been appreciated.

PMID- 22380436
TI  - Immune response increases predation risk.
AB  - Why do individuals have an imperfect immune system? Most studies suggest trade
      offs associated with immunity and metabolism, and neglect ecological factors,
      such as predation. We provide one of the first experimental studies demonstrating
      a context-dependent survival cost to immune activation. In the presence of a
      predator, immune-challenged male field crickets showed significantly lower
      survival than controls, whilst there was no difference in a predator-free
      environment. Immune-challenged males spent more time outside their burrows and
      reacted slower to a simulated predator attack. We conclude that some costs of
      immunity are expressed via increased susceptibility to predation, indicating the
      importance of integrating the ecological context when investigating optimal
      investment in immunity.

PMID- 22380437
TI  - Migratory behavior of birds affects their coevolutionary relationship with blood
      parasites.
AB  - Host traits, such as migratory behavior, could facilitate the dispersal of
      disease-causing parasites, potentially leading to the transfer of infections both
      across geographic areas and between host species. There is, however, little
      quantitative information on whether variation in such host attributes does indeed
      affect the evolutionary outcome of host-parasite associations. Here, we employ
      Leucocytozoon blood parasites of birds, a group of parasites closely related to
      avian malaria, to study host-parasite coevolution in relation to host behavior
      using a phylogenetic comparative approach. We reconstruct the molecular
      phylogenies of both the hosts and parasites and use cophylogenetic tools to
      assess whether each host-parasite association contributes significantly to the
      overall congruence between the two phylogenies. We find evidence for a
      significant fit between host and parasite phylogenies in this system, but show
      that this is due only to associations between nonmigrant parasites and their
      hosts. We also show that migrant bird species harbor a greater genetic diversity
      of parasites compared with nonmigrant species. Taken together, these results
      suggest that the migratory habits of birds could influence their coevolutionary
      relationship with their parasites, and that consideration of host traits is
      important in predicting the outcome of coevolutionary interactions.

PMID- 22380438
TI  - Fitting models of continuous trait evolution to incompletely sampled comparative
      data using approximate Bayesian computation.
AB  - In recent years, a suite of methods has been developed to fit multiple rate
      models to phylogenetic comparative data. However, most methods have limited
      utility at broad phylogenetic scales because they typically require complete
      sampling of both the tree and the associated phenotypic data. Here, we develop
      and implement a new, tree-based method called MECCA (Modeling Evolution of
      Continuous Characters using ABC) that uses a hybrid likelihood/approximate
      Bayesian computation (ABC)-Markov-Chain Monte Carlo approach to simultaneously
      infer rates of diversification and trait evolution from incompletely sampled
      phylogenies and trait data. We demonstrate via simulation that MECCA has
      considerable power to choose among single versus multiple evolutionary rate
      models, and thus can be used to test hypotheses about changes in the rate of
      trait evolution across an incomplete tree of life. We finally apply MECCA to an
      empirical example of body size evolution in carnivores, and show that there is no
      evidence for an elevated rate of body size evolution in the pinnipeds relative to
      terrestrial carnivores. ABC approaches can provide a useful alternative set of
      tools for future macroevolutionary studies where likelihood-dependent approaches
      are lacking.

PMID- 22380439
TI  - Coalescent-based species tree inference from gene tree topologies under
      incomplete lineage sorting by maximum likelihood.
AB  - Incomplete lineage sorting can cause incongruence between the phylogenetic
      history of genes (the gene tree) and that of the species (the species tree),
      which can complicate the inference of phylogenies. In this article, I present a
      new coalescent-based algorithm for species tree inference with maximum
      likelihood. I first describe an improved method for computing the probability of
      a gene tree topology given a species tree, which is much faster than an existing
      algorithm by Degnan and Salter (2005). Based on this method, I develop a
      practical algorithm that takes a set of gene tree topologies and infers species
      trees with maximum likelihood. This algorithm searches for the best species tree
      by starting from initial species trees and performing heuristic search to obtain
      better trees with higher likelihood. This algorithm, called STELLS (which stands
      for Species Tree InfErence with Likelihood for Lineage Sorting), has been
      implemented in a program that is downloadable from the author's web page. The
      simulation results show that the STELLS algorithm is more accurate than an
      existing maximum likelihood method for many datasets, especially when there is
      noise in gene trees. I also show that the STELLS algorithm is efficient and can
      be applied to real biological datasets.

PMID- 22380440
TI  - Evolution of stenophagy in spiders (Araneae): evidence based on the comparative
      analysis of spider diets.
AB  - Stenophagy (narrow diet breadth) represents an extreme of trophic specialization
      in carnivores, but little is known about the forces driving its evolution. We
      used spiders, the most diversified group of terrestrial predators, to investigate
      whether stenophagy (1) promoted diversification; (2) was phylogenetically
      conserved and evolutionarily derived state; and (3) was determined either by
      geographical distribution and foraging guild. We used published data on the prey
      of almost 600 species. Six categories of stenophagy were found: myrmecophagy,
      araneophagy, lepidopterophagy, termitophagy, dipterophagy, and crustaceophagy. We
      found that the species diversity of euryphagous genera and families was similar
      to stenophagous genera and families. At the family level, stenophagy evolved
      repeatedly and independently. Within families, the basal condition was oligophagy
      or euryphagy. Most types of stenophagy were clearly derived: myrmecophagy in
      Zodariidae; lepidopterophagy in Araneidae; dipterophagy in Theridiidae. In
      contrast, araneophagy was confined to basal and intermediate lineages, suggesting
      its ancestral condition. The diet breadth of species from the tropics and
      subtropics was less diverse than species from the temperate zone. Diet breadth
      was lower in cursorial spiders compared to web-building species. Thus, the
      evolution of stenophagy in spiders appears to be complex and governed by
      phylogeny as well as by ecological determinants.

PMID- 22380441
TI  - Feature saltation and the evolution of mimicry.
AB  - In Batesian mimicry, a harmless prey species imitates the warning coloration of
      an unpalatable model species. A traditional suggestion is that mimicry evolves in
      a two-step process, in which a large mutation first achieves approximate
      similarity to the model, after which smaller changes improve the likeness.
      However, it is not known which aspects of predator psychology cause the initial
      mutant to be perceived by predators as being similar to the model, leaving open
      the question of how the crucial first step of mimicry evolution occurs. Using
      theoretical evolutionary simulations and reconstruction of examples of mimicry
      evolution, we show that the evolution of Batesian mimicry can be initiated by a
      mutation that causes prey to acquire a trait that is used by predators as a
      feature to categorize potential prey as unsuitable. The theory that species gain
      entry to mimicry through feature saltation allows us to formulate scenarios of
      the sequence of events during mimicry evolution and to reconstruct an initial
      mimetic appearance for important examples of Batesian mimicry. Because feature
      based categorization by predators entails a qualitative distinction between
      nonmimics and passable mimics, the theory can explain the occurrence of imperfect
      mimicry.

PMID- 22380442
TI  - Drivers of hybridization in a 66-generation record of Colias butterflies.
AB  - Hybridization significantly affects the ecology and evolution of numerous plant
      and animal lineages. Most studies have focused on endogenous drivers of
      hybridization and neglected variation in exogenous factors, such as seasonal
      weather patterns. In this study, we take advantage of a unique dataset consisting
      of records of hybridization between the butterflies Colias eurytheme and C.
      eriphyle (Pieridae) for 66 generations (22 years) to investigate the importance
      of seasonal weather on the production and survival of hybrid offspring. Important
      seasonal weather variables for each parental species and hybrid offspring were
      determined using model averaging, and these weather variables, along with
      butterfly abundances, were analyzed using path analysis. The most important
      drivers of hybridization were the abundance of C. eriphyle, summer minimum
      temperature, and spring maximum temperature. In contrast, the abundance of C.
      eurytheme and weather variables prior to the current flight season were
      relatively unimportant for variation in hybrid abundance. Parental abundances
      were mostly driven by weather variables prior to the flight season possibly
      because these variables affect host plant quality. Our results suggest that
      exogenous, climatic factors can influence hybridization in natural systems, and
      that these factors can act both directly on hybrid abundance and indirectly
      through the population dynamics of parental species.

PMID- 22380443
TI  - Population genetic evidence for complex evolutionary histories of four high
      altitude juniper species in the Qinghai-Tibetan Plateau.
AB  - Population genetics data based on multiple nuclear loci provide invaluable
      information to understand demographic, selective, and divergence histories of the
      current species. We studied nucleotide variation at 13 nuclear loci in 53
      populations distributed among four closely related, but morphologically distinct
      juniper species of the Qinghai-Tibetan Plateau (QTP). We used a novel approach
      combining Approximate Bayesian Computation and a recently developed neutrality
      test based on the maximum frequency of derived mutations to examine the
      demographic and selective histories of individual species, and isolation-with
      migration analyses to study the joint history of the species and detect gene flow
      between them. We found that (1) the four species, which diverged in response to
      the extensive QTP uplifts, have different demographic histories; (2) two loci,
      Pgi and CC0822, depart significantly from neutrality in one species and Pgi, is
      also marginally significant in another; and (3) shared polymorphisms are common,
      indicating both incomplete lineage sorting and gene flow after species
      divergence. In addition, the detected unidirectional gene flow provides indirect
      support for the theoretical prediction that introgression should mostly take
      place from local to invading species. Our results, together with previous
      studies, underscore complex evolutionary histories of plant diversification in
      the biodiversity-hotspot QTP.

PMID- 22380444
TI  - Delimiting species using multilocus data: diagnosing cryptic diversity in the
      southern cavefish, Typhlichthys subterraneus (Teleostei: Amblyopsidae).
AB  - A major challenge facing biodiversity conservation and management is that a
      significant portion of species diversity remains undiscovered or undescribed.
      This is particularly evident in subterranean animals in which species
      delimitation based on morphology is difficult because differentiation is often
      obscured by phenotypic convergence. Multilocus genetic data constitute a valuable
      source of information for species delimitation in such organisms, but until
      recently, few methods were available to objectively test species delimitation
      hypotheses using genetic data. Here, we use recently developed methods for
      discovering and testing species boundaries and relationships using a multilocus
      dataset in a widely distributed subterranean teleost fish, Typhlichthys
      subterraneus, endemic to Eastern North America. We provide evidence that species
      diversity in T. subterraneus is currently underestimated and that the picture of
      a single, widely distributed species is not supported. Rather, several
      morphologically cryptic lineages comprise the diversity in this clade, including
      support for the recognition of T. eigenmanni. The high number of cryptic species
      in Typhlichthys highlights the utility of multilocus genetic data in delimiting
      species, particularly in lineages that exhibit slight morphological disparity,
      such as subterranean organisms. However, results depend on sampling of
      individuals and loci; this issue needs further study.

PMID- 22380445
TI  - Adaptive divergence in moor frog (Rana arvalis) populations along an
      acidification gradient: inferences from Q(st) -F(st) correlations.
AB  - Microevolutionary responses to spatial variation in the environment seem
      ubiquitous, but the relative role of selection and neutral processes in driving
      phenotypic diversification remain often unknown. The moor frog (Rana arvalis)
      shows strong phenotypic divergence along an acidification gradient in Sweden. We
      here used correlations among population pairwise estimates of quantitative trait
      (P(ST)  or Q(ST)  from common garden estimates of embryonic acid tolerance and
      larval life-history traits) and neutral genetic divergence (F(ST)  from neutral
      microsatellite markers), as well as environmental differences (pond pH, predator
      density, and latitude), to test whether this phenotypic divergence is more likely
      due to divergent selection or neutral processes. We found that trait divergence
      was more strongly correlated with environmental differences than the neutral
      marker divergence, suggesting that divergent natural selection has driven
      phenotypic divergence along the acidification gradient. Moreover, pairwise P(ST)
      s of embryonic acid tolerance and Q(ST) s of metamorphic size were strongly
      correlated with breeding pond pH, whereas pairwise Q(ST) s of larval period and
      growth rate were more strongly correlated with geographic distance/latitude and
      predator density, respectively. We suggest that incorporating measurements of
      environmental variation into Q(ST) -F(ST)  studies can improve our inferential
      power about the agents of natural selection in natural populations.

PMID- 22380446
TI  - Chromosomal rearrangements do not seem to affect the gene flow in hybrid zones
      between karyotypic races of the common shrew (Sorex araneus).
AB  - Chromosomal rearrangements are proposed to promote genetic differentiation
      between chromosomally differentiated taxa and therefore promote speciation. Due
      to their remarkable karyotypic polymorphism, the shrews of the Sorex araneus
      group were used to investigate the impact of chromosomal rearrangements on gene
      flow. Five intraspecific chromosomal hybrid zones characterized by different
      levels of karyotypic complexity were studied using 16 microsatellites markers. We
      observed low levels of genetic differentiation even in the hybrid zones with the
      highest karyotypic complexity. No evidence of restricted gene flow between
      differently rearranged chromosomes was observed. Contrary to what was observed at
      the interspecific level, the effect of chromosomal rearrangements on gene flow
      was undetectable within the S. araneus species.

PMID- 22380447
TI  - Evolution in response to social selection: the importance of interactive effects
      of traits on fitness.
AB  - Social interactions have a powerful effect on the evolutionary process. Recent
      attempts to synthesize models of social selection with equations for indirect
      genetic effects (McGlothlin et al. 2010) provide a broad theoretical base from
      which to study selection and evolutionary response in the context of social
      interactions. However, this framework concludes that social selection will lead
      to evolution only if the traits carried by social partners are nonrandomly
      associated. I suggest this conclusion is incomplete, and that traits that do not
      covary between social partners can nevertheless lead to evolution via interactive
      effects on fitness. Such effects occur when there are functional interactions
      between traits, and as an example I use the interplay in water striders
      (Gerridae) between grasping appendages carried by males and spines by females.
      Functional interactive effects between traits can be incorporated into both the
      equations for social selection and the general model of social evolution proposed
      by McGlothlin et al. These expanded equations would accommodate adaptive
      coevolution in social interactions, integrate the quantitative genetic approach
      to social evolution with game theoretical approaches, and stimulate some new
      questions about the process of social evolution.

PMID- 22380448
TI  - Tolerance requires the right smell: first evidence for interspecific selection on
      chemical recognition cues.
AB  - The integument of insects is generally covered with cuticular hydrocarbons (CHC).
      They serve multiple functions, most prominent among them waterproofing and
      especially among social insects-as communication signal. CHC profiles are
      incredibly diverse within and across species. However, the causes for CHC
      variation between species, and potential selection pressures that may shape CHC
      profiles, are hardly understood. Here, we investigated potential selection
      pressures on ant CHC. We tested the hypotheses that living in association with
      another species (e.g., parabiosis), and the climate of the ant's habitat, affect
      CHC composition. We conducted a large-scale comparison of 37 Camponotus species
      from five continents. Our results demonstrate that closely associated ant species
      possess significantly longer hydrocarbons and higher proportions of
      methylbranched alkenes and alkadienes than non- or loosely associated species. In
      contrast, climatic factors had no effects. This study shows that the need to be
      tolerated by another species greatly affects CHC profiles.

PMID- 22380449
TI  - Male-mediated effects on female meiotic recombination.
AB  - Recombination rates vary owing to an individual's genetic composition and/or its
      environmental condition. Yet, the effects of mating partner on recombination
      rates have not been considered. Here, I document a previously undescribed, male
      mediated effect on female recombination rates. After crossing females to males
      from different genetic backgrounds, I observed a significant difference in
      proportion of recombinant offspring based on the genetic background of the father
      (P= 0.0292; df = 3; F= 3.07). Genetic variation in male ability to affect
      recombination rate in their mates suggests the potential for sexual conflict on
      optimal proportion of recombinant offspring, perhaps leading to changes in
      population-level recombination rates with varying levels of sexual selection.

PMID- 22380450
TI  - Predation-associated differences in sex linkage of wild guppy coloration.
AB  - Evolutionary theory predicts that the sex linkage of sexually selected traits can
      influence the direction and rate of evolutionary change, and also itself be
      subject to selection. Theory abounds on how sex-specific selection, mate choice,
      or other phenomena should favor different types of sex-linked inheritance, yet
      evidence in nature remains limited. Here, we use hormone assays in Trinidadian
      guppies to explore the extent to which linkage of male coloration differs among
      populations adapted to varying predation regimes. Results show there is
      consistently higher degree of X- and autosomal linkage in body coloration among
      populations adapted to low-predation environments. More strikingly, analyses of
      an introduced population of guppies from a high- to a low-predation environment
      suggest that this difference can change in 50 years or less.

PMID- 22380451
TI  - The effect of variable frequency of sexual reproduction on the genetic structure
      of natural populations of a cyclical parthenogen.
AB  - Cyclical parthenogens are a valuable system in which to empirically test
      theoretical predictions as to the genetic consequences of sexual reproduction in
      natural populations, particularly if the frequency of sexual relative to asexual
      reproduction can be quantified. In this study, we used a series of lake
      populations of the cyclical parthenogen, Daphnia pulicaria, that vary
      consistently in their investment in sexual reproduction, to address the questions
      of whether the ecological variation in investment in sex is detectable at the
      genetic level, and if so, whether the genetic patterns seen are consistent with
      theoretical predictions. We show that there is variation in the genetic structure
      of these populations in a manner consistent with their investment in sexual
      reproduction. Populations engaging in a high frequency of sex were in Hardy
      Weinberg and gametic phase equilibrium, and showed little genotypic
      differentiation across sampled years. In contrast, populations with a lower
      frequency of sex deviated widely from equilibrium, had reduced multilocus clonal
      diversity, and showed significant temporal genotypic deviation.

PMID- 22380452
TI  - Evolution of ASPM is associated with both increases and decreases in brain size
      in primates.
AB  - A fundamental trend during primate evolution has been the expansion of brain
      size. However, this trend was reversed in the Callitrichidae (marmosets and
      tamarins), which have secondarily evolved smaller brains associated with a
      reduction in body size. The recent pursuit of the genetic basis of brain size
      evolution has largely focused on episodes of brain expansion, but new insights
      may be gained by investigating episodes of brain size reduction. Previous results
      suggest two genes (ASPM and CDK5RAP2) associated with microcephaly, a human
      neurodevelopmental disorder, may have an evolutionary function in primate brain
      expansion. Here we use new sequences encoding key functional domains from 12
      species of callitrichids to show that positive selection has acted on ASPM across
      callitrichid evolution and the rate of ASPM evolution is significantly negatively
      correlated with callitrichid brain size, whereas the evolution of CDK5RAP2 shows
      no correlation with brain size. Our findings strongly suggest that ASPM has a
      previously unsuspected role in the evolution of small brains in primates. ASPM is
      therefore intimately linked to both evolutionary increases and decreases in brain
      size in anthropoids and is a key target for natural selection acting on brain
      size.

PMID- 22380453
TI  - Genetic variation for antibiotic persistence in Escherichia coli.
AB  - Bacterial persistence describes a heterogeneous response to antibiotics in clonal
      populations of bacteria due to phenotypic variation within the population, with a
      small proportion of cells surviving treatment even at very high concentrations of
      drug. The aim of this study was to determine whether different natural isolates
      of Escherichia coli, selected at random from a collection representing the
      spectrum of genetic diversity in the species, generate different fractions of
      persister cells. Despite comparable minimum inhibitory concentrations (MICs) to
      the antibiotics between the different strains, highly significant variation was
      observed in persister fractions following exposure to ampicillin, streptomycinm,
      or norfloxacin. Survival following treatment with one drug did not, however,
      correlate with survival against another. Finally, using competition assays we
      quantify fitness benefits of persistence. These results show that different
      strains of E. coli vary markedly in their response to antibiotics despite
      comparable genetic susceptibility and indicate different mechanisms of evolved
      persistence to different antibiotics.

PMID- 22380454
TI  - Inbreeding and haploid chromosomes: a response to Hedrick (2011).
AB  - We have shown that inbreeding allows maternally transmitted organelles to respond
      to selection on male-specific fitness effects (Wade and Brandvain 2009, see also
      Unckless and Herren 2009). Hedrick (2011) confirms our results, but takes issue
      with our characterization of "inbreeding" at mitochondrial loci. The reason for
      this disagreement is straightforward-we define inbreeding as the process of
      mating between relatives, whereas Hedrick (2011) defines inbreeding as increased
      homozygosity at autosomal loci genome-wide, which occurs because of mating
      between relatives. Here, we insist that our definition is not incorrect, and
      highlight some benefits of our view.

PMID- 22380455
TI  - Angiogenic factors and pregnant woman with new onset seizures.
AB  - BACKGROUND: In patients with new onset seizures during pregnancy, it can be
      challenging to differentiate between eclampsia and other etiologies. Soluble fms
      like tyrosine kinase (sFlt1) is an antiangiogenic protein that is elevated in
      preeclampsia and eclampsia. CASE: A multiparous woman presented at 22 weeks
      gestation with seizures. The initial presentation was highly suspicious for
      eclampsia, but blood pressure and laboratory data were equivocal. Further
      investigation suggested primary seizure disorder. Serum sFlt1 was normal for
      gestational age, supporting the exclusion of eclampsia. CONCLUSION: History,
      physical exam, and traditional laboratory data are the mainstays of eclampsia
      diagnosis; however, sFlt1 may help clinicians when the diagnosis is uncertain at
      preterm gestational ages.

PMID- 22380456
TI  - Fungal/bacterial interactions during the biodegradation of TEX hydrocarbons
      (toluene, ethylbenzene and p-xylene) in gas biofilters operated under xerophilic
      conditions.
AB  - The treatment of air contaminated with toluene, ethylbenzene, and p-xylene was
      assayed in three laboratory-scale biofilters, each consisting of two modules
      connected in series, packed with a pelletized organic fertilizer and inoculated
      with a toluene-degrading liquid enrichment culture. Biofilters were operated in
      parallel for 185 days in which the volumetric organic loading rate was
      progressively increased. The operation regime was subjected to drying out, so
      that packing humidity generally remained below 40%. Significant process failure
      occurred with ethylbenzene and p-xylene, but the toluene biofilter comparatively
      sustained a significant elimination capacity. Microbial community
      characterization by quantitative PCR and denaturing gradient gel electrophoresis
      showed substantial fungal enrichment in the toluene biofilter. Ribotypes
      identical to the well-known toluene-degrading black yeast Exophiala oligosperma
      (Chaetotyriales) were found among the dominant species. The microbial community
      structure was similar in the biofilters loaded with toluene and ethylbenzene but
      with p-xylene was quite specific and encompassed other chaetothyrialean fungi.
      Several species of Actinomycetales were found in the packing while the inoculum
      was dominated by representatives of the Burkholderiales and Xanthomonadales. One
      single fungal ribotype homologous to Acremonium kiliense was detected in the
      inoculum. The implications of xerophilic biofilter operation on process biosafety
      and efficiency are discussed.

PMID- 22380457
TI  - Residue depletion of decoquinate in chicken tissues after oral administration.
AB  - A rapid, sensitive, and reliable high-performance liquid chromatography tandem
      mass spectrometry (LC-MS/MS) method was developed and validated for the analysis
      of decoquinate in chicken tissues. The compounds were extracted using
      acetonitrile by liquid-liquid extraction (LLE) and purified with an Oasis(TM) HLB
      solid-phase extraction (SPE) cartridge. Chromatographic separation was performed
      on an XTerra C18 reversed-phase column with a mobile phase of water containing
      0.1% formic acid and acetonitrile. The analyte was detected by tandem quadrupole
      mass spectrometry after positive electrospray ionization by multiple reaction
      monitoring. The detection and quantitation limits were 1 and 2.5 MUg/kg,
      respectively. The recoveries of edible tissues ranged from 85.3% to 104.9%, with
      relative standard deviations (RSD) lower than 10.4%. The depletion profile of
      decoquinate was studied in healthy chickens after oral administration of feed
      containing 27.2 mg/kg decoquinate for 10 consecutive days. The residue
      concentrations of decoquinate in chicken muscle and liver were detected using the
      developed method. The highest residue concentrations were attained 0.25 day post
      treatment, and decoquinate residues were still detected 5 days postmedication in
      the tissues examined. The developed method has been successfully applied to the
      depletion study of decoquinate in chicken tissues. The recommended withdrawal
      period with oral administration based on our research is 3 days.

PMID- 22380458
TI  - The impact of menopause and hormone therapy on nasal resonance.
AB  - The purpose of this study was to investigate the impact of menopause and hormone
      therapy on nasal resonance by comparing premenopausal women and postmenopausal
      women with and without hormone therapy. A total of 147 middle-aged Flemish
      (Dutch)-speaking women participated in the study and were divided into three
      groups: premenopausal women (n =42), and postmenopausal women with (n =63) and
      without (n =42) hormone therapy. Nasal resonance scores of isolated sounds and
      connected speech were measured using the Nasometer. For the isolated sounds as
      well as for the reading texts, no differences were found in nasal resonance
      scores between the three groups (ANCOVA). The results of this study indicate that
      menopause and hormone therapy do not have an impact on the nasal resonance in
      middle-aged women.

PMID- 22380459
TI  - Suicide mortality of suicide attempt patients discharged from emergency room,
      nonsuicidal psychiatric patients discharged from emergency room, admitted suicide
      attempt patients, and admitted nonsuicidal psychiatric patients.
AB  - The suicide mortality rate and risk factors for suicide completion of patients
      who presented to an emergency room (ER) for suicide attempt and were discharged
      without psychiatric admission, patients who presented to an ER for psychiatric
      problems other than suicide attempt and were discharged without psychiatric
      admission, psychiatric inpatients admitted for suicide attempt, and psychiatric
      inpatients admitted for other reasons were examined. The records of 3,897
      patients who were treated at a general hospital in Seoul, Korea, from July 2003
      to December 2006 were reviewed. Forty-three of the 3,897 subjects died by suicide
      during the 2.5-year observation period. Compared to the general Korean
      population, the suicide mortality rate was 82-fold higher for suicide attempt
      patients, admitted; 54-fold higher for suicide attempt patients, discharged; 21
      fold higher for nonsuicidal patients, admitted; and 11-fold higher for
      nonsuicidal patients, discharged. In all four groups, diagnosis of a depressive
      disorder and suicide attempt at presentation were each significant independent
      risk factors for suicide completion. These results highlight the need for suicide
      prevention strategies for depressed patients who present to the ER or are
      admitted to a psychiatric ward after a suicide attempt.

PMID- 22380460
TI  - Diagnostic evaluation and treatment recommendations for dogs with substage-a high
      grade multicentric lymphoma: results of a survey of veterinarians.
AB  - The goal of this study was to survey veterinarians regarding their current
      initial diagnostic and treatment recommendations for dogs with substage-a high
      grade multicentric lymphoma. A written survey was conducted at the 2009
      Veterinary Cancer Society conference asking veterinarians to provide demographic
      information, initial staging diagnostics and treatment recommendations for canine
      lymphoma. The most commonly recommended staging diagnostics were complete blood
      count (100%), chemistry panel (100%), urinalysis (85%), lymph node cytology
      (88%), thoracic radiographs (84%), immunophenotyping (76%) and abdominal
      ultrasound (75%). The most commonly used first-line B-cell protocols combined the
      drugs L-asparaginase, cyclophosphamide, doxorubicin, vincristine and prednisone
      (L-CHOP, 51%). CHOP (30%) and other CHOP-based protocols (12%) were used as well.
      Thirty-one percent of responders treated B- and T-cell lymphomas differently.
      Protocol lengths varied from <= 16 weeks to >2 years. Current staging and
      treatment recommendations for canine lymphoma are varied. Efforts to standardize
      recommendations should be considered.

PMID- 22380461
TI  - Nanosemiconductor-based photocatalytic vapor generation systems for subsequent
      selenium determination and speciation with atomic fluorescence spectrometry and
      inductively coupled plasma mass spectrometry.
AB  - We reported novel Ag-TiO(2)- and ZrO(2)-based photocatalytic vapor generation
      (PCVG) systems as effective sample introduction techniques for further improving
      the sensitivity of the atomic spectrometric determination of selenium for the
      first time, in which the conduction band electron served as a "reductant" to
      reduce selenium species including Se(VI) and convert them directly into volatile
      H(2)Se, which was easily separated from the sample matrix and underwent more
      effectively subsequent atomization and/or ionization. These two PCVG systems
      helped us to overcome the problem encountered in the most conventional KBH(4)/OH(
      )-H(+) system, in that Se(VI) was hardly converted into volatile selenium species
      without the aid of prereduction procedures. The limits of detection (LODs)
      (3sigma) of the four most typical Se(IV), Se(VI), selenocystine ((SeCys)(2)), and
      selenomethionine (SeMet) species were, respectively, down to 1.2, 1.8, 7.4, and
      0.9 ng mL(-1) in UV/Ag-TiO(2)-HCOOH, and 0.7, 1.0, 4.2, and 0.5 ng mL(-1) in
      UV/ZrO(2)-HCOOH with the relative standard deviations (RSDs) lower than 5.1% (n =
      9 at 1 MUg mL(-1)) when using atomic fluorescence spectrometry (AFS) under flow
      injection mode. They reached 10, 14, 18, and 8 pg mL(-1) in UV/Ag-TiO(2)-HCOOH,
      and 6, 7, 10, and 5 pg mL(-1) in UV/ZrO(2)-HCOOH with the RSDs lower than 4.4% (n
      = 9 at 10 ng mL(-1)) when using inductively coupled plasma mass spectrometry
      (ICPMS). After the two PCVG systems were validated using certified reference
      materials GBW(E)080395 and SELM-1, they were applied to determine the total Se in
      the selenium-enriched yeast sample and used as interfaces between high
      performance liquid chromatography (HPLC) and AFS or ICPMS for selenium speciation
      in the water- and/or enzyme-extractable fractions of the selenium-enriched yeast.

PMID- 22380462
TI  - Using imaging methods to interrogate radiation-induced cell signaling.
AB  - There is increasing emphasis on the use of systems biology approaches to define
      radiation-induced responses in cells and tissues. Such approaches frequently rely
      on global screening using various high throughput 'omics' platforms. Although
      these methods are ideal for obtaining an unbiased overview of cellular responses,
      they often cannot reflect the inherent heterogeneity of the system or provide
      detailed spatial information. Additionally, performing such studies with multiple
      sampling time points can be prohibitively expensive. Imaging provides a
      complementary method with high spatial and temporal resolution capable of
      following the dynamics of signaling processes. In this review, we utilize
      specific examples to illustrate how imaging approaches have furthered our
      understanding of radiation-induced cellular signaling. Particular emphasis is
      placed on protein colocalization, and oscillatory and transient signaling
      dynamics.

PMID- 22380463
TI  - Severe overdose of quetiapine treated successfully with extracorporeal life
      support.
AB  - BACKGROUND: Quetiapine is a second-generation antipsychotic drug, used mainly in
      the treatment of psychotic disorders. Overdose is associated with sedation,
      tachycardia and a prolonged QT-interval on the ECG. Cardiovascular symptoms are
      uncommon but in severe cases profound cardiovascular depression may occur.
      OBJECTIVES: To report a case where extracorporeal circulatory support (ECCS) was
      used successfully in severe quetiapine overdose. CASE REPORT: A 40-year-old woman
      was admitted to the emergency department (ED) with reduced consciousness
      apparently due to intoxication. She had a history of schizophrenia and was
      treated with 900 mg of quetiapine daily. In the ED, she presented with
      immeasurable low blood pressure, irregular bradycardia, hypothermia and a Glasgow
      Coma Scale (GCS) of 8. An immunoassay test for tricyclic antidepressive agents
      (TCA) was positive. Despite resuscitation with intravenous fluids, intensive
      vasopressor treatment and renal replacement therapy (CRRT) the patient's
      condition deteriorated. The patient was quickly moved to an intensive care unit
      where ECCS could be instituted. The patient subsequently recovered after 4 days
      in the ICU without any residual symptoms. Further laboratory analysis did not
      confirm the immunoassay finding. CONCLUSIONS: Severe poisoning with quetiapine
      may imitate tricyclic antidepressant poisoning, and drug screening methods may be
      falsely positive for TCA. In case of cardiovascular collapse due to quetiapine
      overdose, ECCS may be life saving.

PMID- 22380464
TI  - Correlating the 31P NMR chemical shielding tensor and the 2J(P,C) spin-spin
      coupling constants with torsion angles zeta and alpha in the backbone of nucleic
      acids.
AB  - Determination of nucleic acid (NA) structure with NMR spectroscopy is limited by
      the lack of restraints on conformation of NA phosphate. In this work, the (31)P
      chemical shielding tensor, the Gamma(P,C5'H5'1) and Gamma(P,C5'H5'2) cross
      correlated relaxation rates, and the (2)J(P,C3'), (2)J(P,C5'), and (3)J(P,C4')
      coupling constants were calculated in dependence on NA backbone torsion angles
      zeta and alpha. While the orientation of the (31)P chemical shielding tensor was
      almost independent of the NA phosphate conformation, the principal tensor
      components varied by up to ~40 ppm. This variation and the dependence of the
      phosphate geometry on torsion angles zeta and alpha had only a minor influence on
      the calculated Gamma(P,C5'H5'1) and Gamma(P,C5'H5'2) cross-correlated relaxation
      rates, and therefore, the so-called rigid tensor approximation was here
      validated. For the first time, the (2)J(P,C) spin-spin coupling constants were
      correlated with the conformation of NA phosphate. Although each of the two J
      couplings was significantly modulated by both torsions zeta and alpha, the
      (2)J(P,C3') coupling could be structurally assigned to torsion zeta and the
      (2)J(P,C5') coupling to torsion alpha. We propose qualitative rules for their
      structural interpretation as loose restraints on torsion angles zeta and alpha.
      The (3)J(P,C4') coupling assigned to torsion angle beta was found dependent also
      on torsions zeta and alpha, implying that the uncertainty in determination of
      beta with standard Karplus curves could be as large as ~25 degrees . The
      calculations provided a unified picture of NMR parameters applicable for the
      determination of NA phosphate conformation.

PMID- 22380465
TI  - Nanotechnology and drug delivery: Getting there is only half of the challenge!
      (Commentary).

PMID- 22380466
TI  - Recent perspectives on nanoneuroprotection & nanoneurotoxicity.

PMID- 22380467
TI  - Gender and duration of untreated psychosis: a systematic review and meta
      analysis.
AB  - AIM: Duration of untreated psychosis (DUP) can influence the prognosis of
      schizophrenia. Previous studies have suggested that gender may influence the
      length of DUP. This study reports the result of the first systematic literature
      review and meta-analysis on the role of gender in influencing DUP in first
      episode psychosis. METHOD: Systematic literature search in PubMed/Medline and
      Ovid/PsychINFO. Twenty-seven studies presenting data on 4721 patients diagnosed
      with psychosis at their first episode (2834 males and 1887 females) were included
      in the analysis. RESULTS: Samples had a higher proportion of males: odds ratio =
      2.5 (95% confidence interval: 1.8-3.3). Mean age at first contact was 25.4 for
      males and 27.5 for females. Patients from non-Western countries were older at
      first contact than patients from Western countries. Average DUP in schizophrenia
      was 64 weeks and did not differ between genders but was shorter in Western
      compared with non-Western countries. CONCLUSION: Earlier age at first contact and
      larger incidence in males support the existence of specific gender differences in
      first-episode psychosis; however, these are not associated with DUP length.

PMID- 22380468
TI  - Case report and review of delayed-interval delivery for dichorionic, diamniotic
      twins with normal development.
AB  - We report a case of delayed-interval delivery of a dichorionic, diamniotic twin
      pregnancy with the survival of both twins. The patient presented at 22 weeks and
      1 day of gestation with vaginal bleeding and preterm labor. Five days later, the
      first twin was born. The second twin remained in utero. The management consisted
      of careful monitoring of both maternal and fetal status. Nine days later, the
      second twin was delivered vaginally. Both twins received full resuscitation and
      immediate life-support intervention; at 7 years of age both twins exhibited
      normal development.

PMID- 22380469
TI  - Marathon of eponyms: 24 Xmas (Christmas) disease.
AB  - The use of eponyms has long been contentious, but many remain in common use, as
      discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms
      in diseases of the head and neck is found mainly in specialties dealing with
      medically compromised individuals (paediatric dentistry, special care dentistry,
      oral and maxillofacial medicine, oral and maxillofacial pathology, oral and
      maxillofacial radiology and oral and maxillofacial surgery) and particularly by
      hospital-centred practitioners. This series has selected some of the more
      recognised relevant eponymous conditions and presents them alphabetically. The
      information is based largely on data available from MEDLINE and a number of
      internet websites as noted below: the authors would welcome any corrections. This
      document summarises data about Christmas disease.

PMID- 22380470
TI  - Comparison of statin adherence among beneficiaries in MA-PD plans versus PDPs.
AB  - BACKGROUND: Medicare Part D, which provides prescription drug coverage to
      Medicare beneficiaries, is delivered through either Medicare Advantage
      prescription drug (MA-PD) plans or stand-alone prescription drug plans (PDPs). MA
      PD plans cover both drug therapy and other medical services, whereas PDPs provide
      prescription drug coverage only. Because of the potential substitutability
      between prescription drugs and other medical services, MA-PD plans may make
      greater efforts to improve enrollees' adherence to recommended medications than
      PDPs. Prescription drug benefits are more generous in MA-PD plans than in PDPs.
      OBJECTIVE: To assess statin adherence, comparing Medicare beneficiaries in MA-PD
      plans with those in PDPs. METHODS: We used records from the Chronic Condition
      Warehouse 2007 Prescription Drug Event (PDE) file, associated Plan
      Characteristics files, and the Beneficiary Summary File (BSF) for a 5% random
      sample of Medicare beneficiaries. The study sample comprised Medicare
      beneficiaries aged 65 years or older in 2006 who filled at least 1 prescription
      for a statin during 2007, excluding beneficiaries with low-income subsidy or end
      stage renal disease and those without both Medicare Part A and Part B enrollment
      in 2007. Medication adherence was measured by medication possession ratio (MPR),
      defined as the sum of days supply for all statin prescriptions filled in 2007
      minus the days supply that would have carried over into 2008 from the final 2007
      prescription filled, divided by the total number of days from the fill date of
      the first statin prescription to December 31, 2007. A binary indicator of good
      adherence was defined as MPR exceeding 80%. Propensity-score matching was used to
      reduce differences in observed characteristics of enrollees in MA-PD plans and
      PDPs. The propensity score was based on sociodemographic characteristics and
      health risk measures, including Hierarchical Condition Category (HCC) scores.
      RESULTS: In the unmatched sample, the mean MPR was 70.57% for MA-PD enrollees
      versus 70.54% for PDP enrollees (P = 0.780), and the proportion of enrollees with
      good adherence was 46.7% for MA-PD plans versus 46.9% for PDPs (P = 0.262). In
      the matched sample, statin adherence was slightly better among MA-PD enrollees
      than PDP enrollees. Mean MPRs were 70.80% and 69.44%, and the percentages of
      enrollees with good adherence were 47.0% and 45.3% in MA-PD plans and PDPs,
      respectively (both P  less than  0.001). CONCLUSIONS: During an early year of the
      Part D program, MA-PD enrollees had slightly better adherence to statin therapy
      than PDP enrollees. While the difference was statistically significant, it was
      very small and unlikely to lead to clinically meaningful consequences. Less than
      one-half of MA-PD and PDP enrollees had good adherence in statin use, suggesting
      room for improvement in both types of Part D plans. Continuing evaluations of
      adherence in diverse therapy classes are needed for Medicare Part D
      beneficiaries.

PMID- 22380471
TI  - Pharmacy participation and claim characteristics in the Wisconsin Medicaid
      Pharmaceutical Care Program from 1996 to 2007.
AB  - BACKGROUND: Under the 1995 Wisconsin Act 27, the biennial budget, Wisconsin
      Medicaid was required to develop an incentive-based pharmacy payment system for
      pharmaceutical care (PC) services. Started on July 1, 1996, the Wisconsin
      Medicaid Pharmaceutical Care Program (WMPCP) is the longest currently ongoing
      Medicaid program to compensate pharmacists for nondispensing services. The
      program reimburses pharmacies for providing PC services that increase patient
      compliance or prevent potential adverse drug problems by paying an enhanced PC
      dispensing fee. Pharmacists can bill for PC services provided to Wisconsin
      Medicaid fee-for-service and SeniorCare (i.e., state prescription drug assistance
      program for low-income seniors) beneficiaries. OBJECTIVES: To examine trends in
      (a) the number of pharmacies participating in the WMPCP and the intensity of
      participation among participating pharmacies; and (b) frequencies of reason,
      action, result, and level-of-service (time) codes associated with PC service
      claims from July 1, 1996, through June 30, 2007, which represents Wisconsin state
      fiscal years (SFYs) 1997 through 2007. METHODS: A retrospective, longitudinal,
      and descriptive research design was used to analyze all paid claims for PC
      services provided to Wisconsin Medicaid fee-for-service and SeniorCare recipients
      during SFYs 1997 through 2007. The total number of paid PC claims and the average
      number of claims paid per pharmacy were examined to determine trends in pharmacy
      participation. Mean annual reimbursement amounts for PC per claim and per
      pharmacy were calculated. Reason, action, result, and level-of-service (time)
      codes that appeared in the claims were grouped into categories and analyzed to
      characterize the total number of claims paid overall and per SFY. RESULTS: During
      the study period, one-half (n = 601) of the approximately 1,200 licensed
      pharmacies in the state of Wisconsin were paid for a claim through the WMPCP.
      However, intensity of participation in the WMPCP was low, with 57% of all
      participating pharmacies being paid for 10 or fewer PC claims and 19% paid for
      only 1 PC claim over the 11-year study period. The growth in claims per year
      coupled with smaller growth in the number of participating pharmacies resulted in
      a trend of growth in the mean number of claims per participating pharmacy in the
      program. The proportion of total WMPCP claims accounted for by the top 10
      pharmacies with the highest volume of PC claims varied from 46.6% to 80.2% per
      year. Patient behaviors (e.g., early or late refills) and drug use
      issues/problems (e.g., patient complaints or symptoms) were the most common
      reasons for pharmacists to provide PC services (62% of all PC claims), although
      drug choice reasons (e.g., product selection opportunity) were more common after
      2004. The majority (55.1%) of PC services took 15 minutes or less of pharmacists'
      time. The total dollar amount paid to pharmacies for PC services was $876,822
      between SFYs 1997 and 2007, with an overall mean of $1,459 paid per participating
      pharmacy. CONCLUSIONS: Trends in pharmacy participation and claims volume showed
      growth, albeit limited, in PC program participation with a majority of paid
      claims dealing with patient behaviors and drug use issues or problems that
      consumed a small amount of pharmacists' time (15 minutes or less). The intensity
      of participation (claims per pharmacy) increased over time, suggesting that some
      pharmacies may have developed effective systems for participating and
      successfully submitting claims to WMPCP for enhanced dispensing fees. Further
      evaluation of the impact and implications of this program for patients,
      pharmacists, and the state is needed to gauge overall program success and provide
      evidence or guidance for continued or expanded PC initiatives.

PMID- 22380472
TI  - Association between prescription cost sharing and adherence to initial
      combination antiretroviral therapy in commercially insured antiretroviral-naive
      patients with HIV.
AB  - BACKGROUND: In treatment of human immunodeficiency virus (HIV), high levels of
      adherence to combination antiretroviral therapy (cART) are required to prevent
      failure of virologic suppression, development of drug resistance, and permanent
      loss of therapeutic options. No published research has assessed the association
      between cART prescription cost sharing and adherence to cART. OBJECTIVE: To
      analyze the association between cART prescription cost sharing and adherence to
      initial cART in commercially insured antiretroviral (ARV)-naive patients with
      HIV. METHODS: This retrospective observational cohort study used 2002-2008 data
      from a large U.S. claims database of more than 56 million commercially insured
      individuals. Study subjects were patients aged 18 years or older who initiated
      cART during the period January 1, 2003, to December 31, 2007, had no ARV claims
      during the 6-month period prior to the initiation date, and had at least 1 ICD-9
      CM diagnosis code for HIV infection (042, 795.71, V08) from 12 months before to
      12 months after cART initiation. A minimum 12-month period of continuous
      enrollment after cART initiation was used to construct a patient-quarter repeated
      measures panel dataset in which each quarter of data that a patient contributed
      represented an observation. The evaluation period extended from cART initiation
      until the occurrence of 1 of the following events: addition of an ARV that was
      not part of the initial cART regimen, 30-day gap in possession of an ARV within
      the initiated cART regimen, hospitalization of 30 or more days, loss to follow-up
      due to study end (December 31, 2008), or disenrollment. The study's outcome was
      quarterly adherence to cART, defined as the number of days within the quarter
      that a patient possessed all components of the initial cART regimen. Each
      patient's cART cost-sharing amount was calculated per 30-day supply of the entire
      cART regimen. Adherence was dichotomized for analysis at the clinically
      meaningful thresholds of 95% and 78%. The dichotomized adherence outcomes were
      separately modeled using population-averaged generalized estimating equations
      (GEEs) with time-varying and time-constant covariates and an exchangeable working
      correlation structure. Independent variables included cost-sharing amount;
      sequential quarter number after cART initiation; interaction between cost-sharing
      amount and sequential quarter number (to capture any changes in the association
      of cost sharing with adherence that may occur over time after initiation of
      cART); and patient demographic, clinical, and insurance characteristics. For each
      sequential quarter after cART initiation, the GEE models were used to generate
      average predicted probabilities of adherence reaching each threshold (95% and
      78%) at cost-sharing levels of $25, $75, and $144, which represented the 25th,
      75th, and 90th percentiles of the cost-sharing distribution, respectively.
      RESULTS: The study sample included 19,199 patient-quarters and 3,731 patients:
      mean age 41.1 years; 83.2% male; mean (SD) duration of post-index period 5.1
      (4.2) quarters; mean (SD) daily cART pill count 3.2 (2.2); mean (median) cost
      sharing per 30-day supply of the entire cART regimen $67 ($40). In the unadjusted
      analyses of patient-quarters, mean adherence ranged from 97.2% for cost-sharing
      levels within the 0-20th percentiles (from $0 to $20 per 30-day cART supply) to
      94.0% for cost-sharing levels exceeding the 80th percentile (from $84 to $3,832
      per 30-day cART supply). In the adjusted analyses for the second quarter (25th
      percentile of follow-up duration, n = 3,117 cases still under observation) at the
      cost-sharing levels of $25, $75, and $144, the predicted probabilities of at
      least 95% adherence were 0.782, 0.770, and 0.752, respectively, and the predicted
      probabilities of at least 78% adherence were 0.936, 0.931, and 0.924,
      respectively. The differences in the predicted probabilities of adherence grew
      over time. By the seventh quarter (the 75th percentile of follow-up duration, n =
      1,096 cases still under observation), the predicted probabilities were 0.773,
      0.746, and 0.707 for 95% adherence and 0.933, 0.922, and 0.904 for 78% adherence
      at cost-sharing levels of $25, $75, and $144, respectively. CONCLUSION:
      Increasing cART prescription cost sharing was associated with modestly decreased
      probability of maintaining clinically meaningful levels of cART adherence.

PMID- 22380473
TI  - VBID, the PPACA, and FREEE medications: Did politics trump the evidence about
      cost sharing?

PMID- 22380474
TI  - Clarification of dalfampridine labeled indications.

PMID- 22380475
TI  - Evidence of a ZnCr2Se4 spinel inclusion at the core of a Cr-doped ZnSe quantum
      dot.
AB  - Herein we report doping of ZnSe by Cr ions leads to formation of small
      ZnCr(2)Se(4) spinel inclusions within the cubic sphalerite lattice of a 2.8 nm
      CrZnSe quantum dot (QD). The Cr ion incorporates as a pair of Cr(III) ions
      occupying edge-sharing tetragonal distorted octahedral sites generated by
      formation of three Zn ion vacancies in the sphalerite lattice in order to charge
      compensate the QD. The site is analogous to the formation of a subunit of the
      ZnCr(2)Se(4) spinel phase known to form as inclusions during peritectoid crystal
      growth in the ternary CrZnSe solid-state compound. The oxidation state and site
      symmetry of the Cr ion is confirmed by X-ray absorption near edge spectroscopy
      (XANES), crystal field absorption spectroscopy, and electron paramagnetic
      resonance (EPR). Incorporation as the Cr(III) oxidation state is consistent with
      the thermodynamic preference for Cr to occupy an octahedral site within a II-VI
      semiconductor lattice with a half-filled t(2g) d-level. The measured crystal
      field splitting energy for the CrZnSe QD is 2.08 eV (2.07 eV form XANES),
      consistent with a spinel inclusion. Further evidence of a spinel inclusion is
      provided by analysis of the magnetic data, where antiferromagnetic (AFM)
      exchange, a Curie-Weiss (C-W) temperature of theta = -125 K, and a nearest
      neighbor exchange coupling constant of J(NN) = -12.5 K are observed. The
      formation of stable spinel inclusions in a QD has not been previously reported.

PMID- 22380476
TI  - Catheter lock technique: in vitro efficacy of ethanol for eradication of
      methicillin-resistant staphylococcal biofilm compared with other agents.
AB  - Biofilm formation in central venous catheters (CVC) is a prerequisite for
      catheter-related bloodstream infection (CRBSI). The catheter lock technique has
      been used to treat biofilm infection, but the ideal agent, concentration and the
      minimum exposure time necessary to eradicate the biofilms are not clearly known.
      In this study, biofilm-producing strains of staphylococci were used to find out
      the minimum biofilm eradication concentration of ethanol compared with three
      other conventional antibacterial agents. Eight representative methicillin
      resistant staphylococci, from colonized CVCs, were studied. The biofilms were
      exposed to 1, 5 and 10 mg mL(-1)  of gentamicin, ciprofloxacin and vancomycin.
      The ethanol concentrations used were 20%, 40% and 80%. Biofilms were examined for
      the presence of live organisms after exposure to these agents from 30 min to 24
      h. The three antibiotics were unable to eradicate the biofilms even after 24 h,
      while ethanol at 40% concentration could do so for all the isolates in 1 h. Our
      study highlights the efficacy and rationale of using 40% ethanol for a short
      period as catheter lock solution to eradicate biofilms and thus to prevent CRBSI,
      instead of using high concentrations of antibiotics for extended periods.

PMID- 22380478
TI  - Virus induced and associated post-translational modifications.

PMID- 22380481
TI  - Models of fetal brain injury, intrauterine inflammation, and preterm birth.
AB  - Intrauterine infection and inflammation are known risk factors for brain damage
      in the neonate irrespective of the gestational age. Infection-induced maternal
      immune activation leads to a fetal inflammatory response mediated by cytokines
      that has been implicated in the development of not only periventricular
      leukomalacia and cerebral palsy but also a spectrum of neurodevelopmental
      disorders such as autism and schizophrenia (Behav Brain Res 2009; 204:313, Ann
      Neurol 2005; 57:67, Am J Obstet Gynecol 2000; 182:675). A common link among the
      neurobehavioral disorders associated with intrauterine inflammation appears to be
      the evidence for immune dysregulation in the developing brain (Behav Brain Res
      2009; 204:313). The timing of the immune challenge with respect to the
      gestational age and neurologic development of the fetus may be crucial in the
      elicited response (J Neurosci 2006; 26:4752). Studies involving animal models of
      maternal inflammation serve a key role in elucidation of mechanisms involved in
      fetal brain injury associated with exposure to the maternal milieu. These animal
      models have been shown to result in fetal microglial activation, neurotoxicity as
      well motor deficits and behavioral abnormalities in the offspring (J Neurosci
      2006; 26:4752, J Neurosci Res 2010; 88:172, Am J Obstet Gynecol 2009; 201:279, Am
      J Obstet Gynecol 2008; 199:651). A better understanding of the mechanisms of
      perinatal brain injury will allow discoveries of novel neuroprotective agents,
      better outcomes following preterm birth and stratification of fetuses and
      neonates for therapies in cases of preterm birth, preterm premature rupture of
      membranes, and chorioamnionitis.

PMID- 22380482
TI  - Four butyrolactones and diverse bioactive secondary metabolites from terrestrial
      Aspergillus flavipes MM2: isolation and structure determination.
AB  - The chemical constituents and biological activities of the terrestrial
      Aspergillus flavipes MM2 isolated from Egyptian rice hulls are reported. Seven
      bioactive compounds were obtained, of which one sterol: ergosterol (1), four
      butyrolactones: butyrolactone I (2), aspulvinone H (3), butyrolactone-V (6) and
      4,4'-diydroxypulvinone (7), along with 6-methylsalicylic acid (4) and the
      cyclopentenone analogue; terrien (5). Structures of the isolated compounds were
      deduced by intensive studies of their 1D & 2D NMR, MS data and comparison with
      related structures. The strain extract and the isolated compounds (1-7) were
      biologically studied against number of microbial strains, and brine shrimp for
      cytotoxicity. In this article, the taxonomical characterization of A. flavipes
      MM2 along with its upscale fermentation, isolation and structural assignment of
      the obtained bioactive metabolites, and evaluate their antimicrobial and
      cytotoxic activities were described.

PMID- 22380483
TI  - Automated systems to identify relevant documents in product risk management.
AB  - BACKGROUND: Product risk management involves critical assessment of the risks and
      benefits of health products circulating in the market. One of the important
      sources of safety information is the primary literature, especially for newer
      products which regulatory authorities have relatively little experience with.
      Although the primary literature provides vast and diverse information, only a
      small proportion of which is useful for product risk assessment work. Hence, the
      aim of this study is to explore the possibility of using text mining to automate
      the identification of useful articles, which will reduce the time taken for
      literature search and hence improving work efficiency. In this study, term
      frequency inverse document-frequency values were computed for predictors
      extracted from the titles and abstracts of articles related to three tumour
      necrosis factors-alpha blockers. A general automated system was developed using
      only general predictors and was tested for its generalizability using articles
      related to four other drug classes. Several specific automated systems were
      developed using both general and specific predictors and training sets of
      different sizes in order to determine the minimum number of articles required for
      developing such systems. RESULTS: The general automated system had an area under
      the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number
      of 'useful' articles among the first 10% and 20% of the articles presented to the
      evaluators when tested on the generalizability set. However, its use may be
      limited by the subjective definition of useful articles. For the specific
      automated system, it was found that only 20 articles were required to develop a
      specific automated system with a prediction performance (AUC 0.748) that was
      better than that of general automated system. CONCLUSIONS: Specific automated
      systems can be developed rapidly and avoid problems caused by subjective
      definition of useful articles. Thus the efficiency of product risk management can
      be improved with the use of specific automated systems.

PMID- 22380484
TI  - ADMET evaluation in drug discovery. 12. Development of binary classification
      models for prediction of hERG potassium channel blockage.
AB  - Inhibition of the human ether-a-go-go related gene (hERG) potassium channel may
      result in QT interval prolongation, which causes severe cardiac side effects and
      is a major problem in clinical studies of drug candidates. The development of in
      silico tools to filter out potential hERG potassium channel blockers in early
      stages of the drug discovery process is of considerable interest. Here, a diverse
      set of 806 compounds with hERG inhibition data was assembled, and the binary hERG
      classification models using naive Bayesian classification and recursive
      partitioning (RP) techniques were established and evaluated. The naive Bayesian
      classifier based on molecular properties and the ECFP_8 fingerprints yielded
      84.8% accuracy for the training set using the leave-one-out (LOO) cross
      validation procedure and 85% accuracy for the test set of 120 molecules. For the
      two additional test sets, the model achieved 89.4% accuracy for the WOMBAT-PK
      test set, and 86.1% accuracy for the PubChem test set. The naive Bayesian
      classifiers gave better predictions than the RP classifiers. Moreover, the
      Bayesian classifier, employing molecular fingerprints, highlights the important
      structural fragments favorable or unfavorable for hERG potassium channel
      blockage, which offers extra valuable information for the design of compounds
      avoiding undesirable hERG activity.

PMID- 22380485
TI  - Cystatin C is a strong predictor of survival in patients with cirrhosis: is a
      cystatin C-based MELD better?
AB  - BACKGROUND/AIMS: The model of end stage liver disease (MELD) includes serum
      creatinine, which is a poor surrogate marker of renal function in patients with
      cirrhosis. Especially in women and patients with advanced disease creatinine
      underestimates true renal function. Our objective was to assess whether or not
      the substitution of creatinine by cystatin C improves the prognostic performance
      of the model. METHODS: The association between MELD parameters and cystatin C
      with survival was investigated using a Cox proportional hazards model. A cystatin
      C-based MELD score was calculated from the results and compared with creatinine
      based MELD in terms of discrimination and calibration. RESULTS: Four hundred and
      twenty-nine patients were included in the study; 19% died and 12% underwent liver
      transplantation during a median follow-up of 602 days. In multivariate Cox
      regression, cystatin C was an independent predictor of 90-day mortality with a
      hazard ratio of 8.0 (95% CI: 2.2-29.6). The median cystatin C-based MELD was 15,
      the median creatinine-based MELD was 12. Calibration and discrimination for 3
      month and 1 year mortality was similar between the scores (AUC > 0.85 for both
      scores). Gender differences in cystatin C-based MELD were less pronounced than
      those in the creatinine-based model, because creatinine but not cystatin C was
      affected by gender. CONCLUSION: Substitution of creatinine by cystatin C does not
      improve the predictive power of MELD.

PMID- 22380486
TI  - Activation of NF-kappaB in placentas of women with preeclampsia.
AB  - OBJECTIVE: Placentas are oxidatively stressed during preeclampsia and produce
      more tumor necrosis factor alpha (TNFalpha) and more thromboxane than normal.
      Oxidative stress may cause these abnormalities by activating nuclear factor
      kappaB (NF-kappaB). We measured the levels of activated NF-kappaB in normal and
      preeclamptic placentas and determined whether oxidative stress activates NF
      kappaB in a trophoblast-like cell line. METHODS: We used immunohistochemistry to
      determine the percentage of the total tissue area that stained for the p65
      subunit of NF-kappaB in placentas obtained from normal and preeclamptic
      pregnancies. In a second set of experiments, we used a reporter plasmid bearing
      the NF-kappaB binding site and transfected it into trophoblast-like cells. The
      cells were incubated with medium control, linoleic acid (LA), an oxidizing
      solution (Ox), or Ox enriched with LA (OxLA), TNFalpha, or OxLA plus TNFalpha for
      20 h. Cell lysates were analyzed using a dual luciferase assay kit. RESULTS:
      Placentas obtained from women with preeclampsia showed nearly a 10-fold increase
      in the extent of area stained for activated NF-kappaB as compared to normal
      placentas. In cell culture experiments, Ox and OxLA induced a threefold increase
      in NF-kappaB activation as compared to medium control or LA. TNFalpha induced a
      threefold increase in NF-kappaB activation. The combination of TNFalpha with OxLA
      caused a 10-fold increase in NF-kappaB activation. CONCLUSIONS: Placental NF
      kappaB is activated nearly 10-fold in preeclampsia. Oxidative stress causes NF
      kappaB activation in a trophoblast-like cell line, which is enhanced by TNFalpha.
      These data suggest that oxidative stress is likely an important in vivo activator
      of placental NF-kappaB in preeclampsia.

PMID- 22380487
TI  - Temporal profiling of the heat-stable proteome during late maturation of Medicago
      truncatula seeds identifies a restricted subset of late embryogenesis abundant
      proteins associated with longevity.
AB  - Developing seeds accumulate late embryogenesis abundant (LEA) proteins, a family
      of intrinsically disordered and hydrophilic proteins that confer cellular
      protection upon stress. Many different LEA proteins exist in seeds, but their
      relative contribution to seed desiccation tolerance or longevity (duration of
      survival) is not yet investigated. To address this, a reference map of LEA
      proteins was established by proteomics on a hydrophilic protein fraction from
      mature Medicago truncatula seeds and identified 35 polypeptides encoded by 16 LEA
      genes. Spatial and temporal expression profiles of the LEA polypeptides were
      obtained during the long maturation phase during which desiccation tolerance and
      longevity are sequentially acquired until pod abscission and final maturation
      drying occurs. Five LEA polypeptides, representing 6% of the total LEA intensity,
      accumulated upon acquisition of desiccation tolerance. The gradual 30-fold
      increase in longevity correlated with the accumulation of four LEA polypeptides,
      representing 35% of LEA in mature seeds, and with two chaperone-related
      polypeptides. The majority of LEA polypeptides increased around pod abscission
      during final maturation drying. The differential accumulation profiles of the LEA
      polypeptides suggest different roles in seed physiology, with a small subset of
      LEA and other proteins with chaperone-like functions correlating with desiccation
      tolerance and longevity.

PMID- 22380488
TI  - Prognostic factors in lung cancer in a defined geographical area over two decades
      with a special emphasis on gender.
AB  - INTRODUCTION: Many studies over recent decades report an increasing incidence of
      lung cancer in female patients. Female gender is often reported as a good
      prognostic factor. OBJECTIVES: The aim of the present study was to investigate
      prognostic factors with a special emphasis on gender. METHODS:   During 1989
      2008, 1497 patients in eastern Scania, a part of southern Sweden with 202,000
      inhabitants, were referred to one Central Hospital and prospectively registered.
      All patients were grouped into four 5-year periods and were analysed for
      occurrence of lung cancer, patient performance status, types and stages of lung
      cancer and the relation to gender. RESULTS: The incidence of lung cancer more
      than doubled in women. The proportion of adenocarcinomas increased in females and
      in males to 57% (P=0.028) and 42% (P=0.001), respectively, while the frequency of
      small cell lung carcinomas (SCLCs) decreased in both genders to approximately
      14%. Females had significantly more frequent stage 1 (16.6%) and higher surgery
      rate (23.1%) than males (12% and 18.2%, respectively). Females showed a higher 5
      year survival rate than males (20.1% and 11.5%, respectively; P<0.001). Patients
      with non-small cell lung carcinoma (NSCLC) had a higher 5-year survival rate than
      those with SCLC (16.5% and 7.5%, respectively; P<0.01); however, there was no
      significant survival difference in females between NSCLC and SCLC. CONCLUSION:
      Female patients exhibited longer survival than males for both NSCLC and SCLC, and
      this was not explained by a higher frequency of stage 1 or surgery in NSCLC.

PMID- 22380489
TI  - Associations between oral health-related quality of life and emotional statuses
      in children and preadolescents.
AB  - OBJECTIVES: To evaluate the associations between oral health-related quality of
      life (OHRQoL) and emotional statuses in children and preadolescents. METHODS: One
      hundred and forty-five Brazilian students (8-14 years) were clinically examined
      for caries, gingivitis, fluorosis, malocclusions, and temporomandibular disorders
      (TMD). OHRQoL was measured using two global ratings of oral health (OH) and
      overall well-being (OWB). The Revised Children's Manifest Anxiety Scale (R-CMAS)
      and Children's Depression Inventory (CDI) were used to assess anxiety and
      depression, respectively. Saliva was collected 30 min after waking and at night
      to determine the diurnal decline in salivary cortisol (DDSC). The results were
      analyzed using non-paired t test/one-way ANOVA, Pearson's correlation test, and
      multiple linear regression analyses. RESULTS: 11-14-year-old participants had
      higher CDI scores (P < 0.01) and DDSC concentrations (P < 0.001). Participants
      with fewer caries and without gingivitis had higher DDSC concentrations (P <
      0.05). TMD patients had higher DDSC concentrations and OWB ratings (P < 0.001).
      Girls had higher Revised Children's Manifest Anxiety Scale (RCMAS) scores (P <
      0.01). There was positive correlation between RCMAS and CDI scores and OWB
      ratings (P < 0.05). The OH model retained age (beta =0.312; P < 0.001) and the
      OWB model retained TMD (beta = 0.271; P < 0.001) and CDI scores (beta=0.175; P <
      0.05). CONCLUSIONS: Children and preadolescents with poor emotional well-being
      are more sensitive to the impacts of OH and its effects on OWB.

PMID- 22380490
TI  - Modified rheokinetic technique to enhance the understanding of microcapsule-based
      self-healing polymers.
AB  - A modified rheokinetic technique was developed to monitor the polymerization of
      healing monomers in a microcapsule-based, self-healing mimicking environment.
      Using this modified technique, monomers active toward ring-opening metathesis
      polymerization (ROMP) were either identified or disregarded as candidates for
      incorporation in self-healing polymers. The effect of initiator loading on the
      quality and speed of healing was also studied. It was observed that self-healing
      polymers have upper and lower temperature limits between which the healing
      mechanism performs at optimal levels. Also, a study of the quality of healing
      cracks of different thicknesses was performed, and it was discovered that above a
      critical crack thickness value, the quality of self-healing diminishes
      substantially; reasons for this phenomenon are discussed in detail.

PMID- 22380491
TI  - Comparison of efficacy of modified electric vacuum aspiration with sharp
      curettage for the treatment of incomplete abortion: randomized controlled trial.
AB  - AIM: The aim of this study was to compare the efficacy of modified electric
      vacuum aspiration (mEVA) and sharp curettage (SC) for treatment of incomplete
      abortion. MATERIAL AND METHODS: A randomized controlled trial was conducted
      between 1 March 2005 and 15 December 2009. Ninety-four women with incomplete
      abortion were randomly allocated into two groups, group A (n = 47) underwent mEVA
      and group B (n=47) underwent SC. The procedures were performed using the
      paracervical block with 20 mL of lidocaine. Successful management and
      complication were assessed. Successful management was defined as complete uterine
      evacuation with no need for the second surgical procedure. RESULTS: There were
      differences in women characteristics between groups. The successful rate of
      management was 100% for both groups. However, the operative time and estimated
      blood loss were less in the mEVA group than in the SC group. Severe pain was
      significantly less prevalent in group A than group B. Suspected endometritis was
      found in two (4.3%) patients in each group. CONCLUSIONS: The efficacy of mEVA was
      the same as that of SC in successful management of incomplete abortion, but pain
      was experienced more often in the SC group.

PMID- 22380492
TI  - Reversible H2 addition across a nickel-borane unit as a promising strategy for
      catalysis.
AB  - We report the synthesis and characterization of a series of nickel complexes of
      the chelating diphosphine-borane ligands ArB(o-Ph(2)PC(6)H(4))(2) ([(Ar)DPB(Ph)];
      Ar = Ph, Mes). The [(Ar)DPB(Ph)] framework supports pseudo-tetrahedral nickel
      complexes featuring eta(2)-B,C coordination from the ligand backbone. For the B
      phenyl derivative, the THF adduct [(Ph)DPB(Ph)]Ni(THF) has been characterized by
      X-ray diffraction and features a very short interaction between nickel and the
      eta(2)-B,C ligand. For the B-mesityl derivative, the reduced nickel complex
      [(Mes)DPB(Ph)]Ni is isolated as a pseudo-three-coordinate "naked" species that
      undergoes reversible, nearly thermoneutral oxidative addition of dihydrogen to
      give a borohydrido-hydride complex of nickel(II) which has been characterized in
      solution by multinuclear NMR. Furthermore, [(Mes)DPB(Ph)]Ni is an efficient
      catalyst for the hydrogenation of olefin substrates under mild conditions.

PMID- 22380493
TI  - Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats.
AB  - OBJECTVES: We investigated whether tacrolimus (FK506) can inhibit neointimal
      formation in arterialised vein grafts in rats. METHODS: Lewis iliolumbar veins
      were implanted into the abdominal aorta of isogeneic rats. Animals in the
      treatment groups had daily intramuscular injections of tacrolimus at 0.2 mg/kg
      (group B) and 0.1 mg/kg (Group C), respectively. The control group A had no
      treatment. Light microscope evaluations of arterialised vein grafts were
      performed 30 days after operation. We determined the presence of endothelial
      cells, the thickness of intima and media, and the degree of infiltration by MHC
      class II positive, CD4 positive, and CD8 positive cells into the adventitia.
      RESULTS: The intimal thickness in group B (5.0+/-1.0 um) was statistically lower
      (P < 0.05) when compared to group C (7.0+/-3.0 um). The intimal thickness in
      untreated group A (12.7+/-7.0 um) was statistically higher (P < 0.01) when
      compared to both treated groups B and C, respectively. The medial thickness and
      degree of adventitial infiltration by MHC class II positive, CD8 positive, and
      CD4 positive cells did not differ between groups. CONCLUSION: Treatment with
      tacrolimus (FK506) showed a dose dependant inhibition of neointimal hyperplasia
      in arterialised vein grafts in rats (Tab. 1, Fig. 3, Ref. 22).

PMID- 22380494
TI  - The effects of dexamethasone on oxidant/antioxidant status in kidneys of rats
      administered mercuric chloride.
AB  - The study was aimed to evaluate the possible effects of dexamethasone on
      oxidant/antioxidant status in kidney tissues of rats administered mercuric
      chloride (HgCl2). Thirty male Wistar-albino rats were enrolled in this study.
      Rats were divided into 4 groups: G1 (n=7) underwent no therapy (control group),
      G2 (n=8) received HgCl2 + physiological saline, G3 (n=7) dexamethasone (DM) +
      physiological saline and G4 (n=8) received HgCl2 + DM. HgCl2 was injected
      subcutaneously into rats in the G2 and G4 on the first day of the study.
      Dexamethasone was injected intraperitoneally into rats in the G3 and G4 for 3
      days. Malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GSH
      Px), xanthine oxidase (XO) and superoxide dismutase (SOD) activities were
      evaluated in the kidney tissues. Serum creatinine levels were also measured.
      Xanthine oxidase activity was increased in the G2 compared to the control group.
      Catalase activity in the control group was significantly higher compared to the
      other groups. In the histopathological examination of kidneys, there was a
      tubular degeneration in G2 and G4. It was concluded that HgCl2 administration may
      cause oxidative stress through increasing XO and decreasing CAT activities.
      Dexamethasone injection may partially protect the rat kidneys against oxidative
      reactions by preventing the increase in XO activity (Tab. 1, Ref. 33).

PMID- 22380495
TI  - Association of angiotensin converting enzyme gene (I/D) polymorphism with
      hypertension and type 2 diabetes.
AB  - OBJECTIVES: This study was conducted to determine the association of
      insertion/deletion (I/D) polymorphism of the ACE gene in hypertensive and T2DM
      subjects in Egyptian population. BACKGROUND: The deletion (D) allele of the
      angiotensin-converting enzyme (ACE) gene has been studied in relation to
      hypertension and type 2 diabetes mellitus (T2DM) with contradictory results which
      might be due to ethnic and geographical variations. METHODS: A total of 85
      subjects participated in this study; hypertension (Group 1); type 2 diabetes
      mellitus (Group 2) and controls (Group 3). Written informed consent was obtained.
      for each subject: age, sex, diabetes duration and the drugs used, blood pressure
      (systolic and diastolic), and lipid profile. Genotyping was performed by
      polymerase chain reaction (PCR). RESULTS: The frequency of DD genotype was
      significantly higher in hypertensive (60 %) and diabetic patients (68 %) compared
      to controls (33.3 %) (p=0.04, p=0.01 respectively). The DD genotype (vs DI and II
      genotype) in the hypertensive and diabetic groups is associated with increased
      risk of hypertension and/or diabetes. OR=3.00; 95%, Cl = 0.993-9.067; OR=4.250;
      95%, Cl = 1.234-14.63 respectively). The D allele was more frequent in
      hypertensive (77.5 %) and diabetic patients (82 %) compared to controls (52.4 %)
      (p=0.004 and 0.002 respectively). The D allele (vs the I allele) is associated
      with increased risk of hypertension and diabetes OR=3.13, 95%Cl=1.405-6.978; OR=
      4.14, 95% CI= 1.615-10.622 respectively). CONCLUSION: The DD genotype and the D
      allele are associated with hypertension and type 2 diabetes in Egyptian patients
      (Tab. 5, Fig. 1, Ref. 32).

PMID- 22380496
TI  - The variant translocation of ABL1 gene t(2;9)(q21;q34) in a childhood T-cell
      acute lymphoblastic leukemia.
AB  - We present the case of the childhood ALL that was identified by the translocation
      of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11)
      translocation. The observation of a poor clinical course of the case may
      contribute to explanation of the action of t(9;22)(q34;q11) translocation, of
      which poor prognostic action is known on ALL's, in terms of ABL1 gene,
      independent of the BCR gene. On the other hand, the prognostic significance of
      this variant ABL1 translocation detection, which is very rarely observed, will
      cast a light on future cases (Tab. 1, Fig. 1, Ref. 11).

PMID- 22380497
TI  - Ratio of lipid parameters to coenzyme Q10 could be used as biomarker of the
      development of early complications of obesity in children.
AB  - BACKGROUND: Chronic obesity is associated with reduced levels of antioxidants,
      increased free oxygen radicals, and oxidative stress. Child obesity may lead to
      the development of complications, such as changes in metabolism, metabolic
      syndrome, neurological, cardiological, respiratory, renal, gastrointestinal,
      endocrinological, and musculoskeletal conditions. The aim of the present study is
      to establish whether there is a correlation between basal CoQ10 plasma
      concentration and the ratio of lipid parameters to CoQ10 in obese children.
      METHODS: The study included 101 obese children and 20 non-obese children, aged 10
      18 years. Antioxidants - CoQ10-OX, alpha-tocopherol, beta-carotene - in plasma
      were measured by HPLC method with UV detector, and plasma malondialdehyde
      spectrophotometrically. RESULTS: High correlation was found between plasma
      concentration of CoQ10 and the ratio of total Chol/CoQ10-OX as well as between
      CoQ10-OX and the ratio of HDL Chol/CoQ10 in plasma of obese children. The lowest
      correlation was between plasma concentration of CoQ10-OX and the ratio of LDL
      Chol/CoQ10 , as well as between CoQ10-OX and the ratio of TAG/CoQ10 in obese
      children. CONCLUSION: An increase of the ratios of lipid parameters to CoQ10 is
      associated with child obesity and could be used as biomarkers of early
      complications in the development of obesity in children (Tab. 3, Fig. 5, Ref.
      22).

PMID- 22380498
TI  - Psychoactive substances related to the deaths.
AB  - The study included all deceased who died in relation to psychoactive substances
      abuse in the regions of Bratislava and Trnava city districts within a two-year
      period of the years 2007-2008. All the cases were autopsied by the standard
      method completed with toxicological analyses. There were reported total 84
      fatalities related to psychoactive substances. From this amount, 38 cases (45 %)
      belong to the group of direct deaths (poisonings) and 46 cases (55 %) to the
      group with other cause of death. Out of the total number, 83 % were related to
      men and 17 % to women. More than 50 % of the cases were related to the age up to
      34 years. In the group of poisonings, the most frequently detected substances
      were opioids themselves or in combination with other substances in 53 %. In the
      group of the indirect deaths, the most frequent category of death was suicide in
      39 %. The most frequently detected psychoactive substances were central nervous
      system stimulants in 40 % of cases (Tab. 6, Fig. 1, Ref. 16).

PMID- 22380499
TI  - Local recurrence rate in patients with DCIS.
AB  - The aim of this observational retrospective study was to evaluate the local
      recurrence rate of ductal carcinoma in situ of the breast (DCIS) and/or invasive
      breast cancer in patients with DCIS or microinvasive carcinoma of the breast
      after breast conserving or radical surgery. Secondary aim of the study was
      comprehensive assessment of the whole management of DCIS and its comparison with
      European guidelines. METHODS: The study was performed in a group of 41 women with
      DCIS or microinvasive cancer, who underwent surgical treatment (breast conserving
      or radical modified mastectomy) at the IInd Department of Gynaecology and
      Obstetrics, University Hospital Bratislava (UNB), during the period 2001-2009.
      Documentation and pathological examination data from paraffin embedded tissue
      sections were used as data source. We sent out questionnaires regarding data
      about additional postoperative treatment and course of the disease up to year
      2010 with focus on recurrence or tumour de novo incidence. RESULTS: Breast
      conserving surgery was performed in 28 cases - 68 %, modified radical mastectomy
      in 13 cases. All cases of mastectomy were due to multicentricity and/or extensive
      tumour >4 cm. Additional surgery due to unsatisfactory marginal status was
      performed in 8 patients (3.28 %). Additional treatment such as radiotherapy
      and/or hormonal therapy received 19 patients. Van Nuyss Prognostic Index was
      reported in 17 patients on the basis of histopathological data. 27 patients
      completed and returned questionnaire. No DCIS recurrence nor infiltrating cancer
      or tumour de novo was reported in this group. CONCLUSION: We consider surgical
      management as adequate. Further material analysis is needed (Tab. 5, Fig. 1, Ref.
      28).

PMID- 22380500
TI  - Trauma in surgery and its incidence, circumstances as well as clinical
      consequences.
AB  - This study was conducted from 10.02.08 to 23.05.09 in general surgery wards of
      Chittagong Medical College Hospital, Bangladesh with multi-factorial views of
      clinical aspects and an alarming model image in such relation was depicted. 188
      (72.9 %) patients in this study out of 258 were male it was and found that
      different types of trauma had been relatively higher in 51-70 yrs (35.1 %) age
      group followed by 31-50 yrs (28.7 %) age group in case of male subjects. On the
      contrary, in female, those were quite higher in 11-30 yrs (31.4 %) age group
      followed by 51-70 yrs (24.8 %) age group. As for the mortality, this study
      suggest that it was significantly higher in case of female subjects (31.4 %) (22)
      in relation to male subjects (18.1 %) (34). But to our knowledge probably it has
      no clinical significance at all. Rather, it may have socio-economic associations,
      as for instance- traditional negligence to female in developing countries like
      Bangladesh. Another remarkable observation that was clear in this study was
      variation in different levels of morbidity. In male, 30.9 % patients had
      morbidity from 1 week to 1 month; followed by 28.7 % patients with morbidity less
      than 1 week, whereas, in case of female, it was 25.7 % and 20 %, respectively.
      With regard to morbidity over 1 month 23.4 % male and 22.9 % female were found in
      this group and in case of both male and female, the so called p-values were quite
      significant. This study also reflects that majority of trauma occurred due to
      road traffic accidents (RTAs) (24.5 %) followed by natural disasters (21.3 %) and
      assault (17 %) in case of male, whereas, in female 34.3 % trauma occurred by
      assault and homicidal attempts followed by 20 % due to natural disaster. One of
      the most remarkable associations of traumatic patients was that 82.3 % (28) of
      all deaths occurred in the first 24 hours of injury in male and on the other
      hand, it was 72.7 % (16) in case of female patients (Tab. 3, Fig. 7, Ref. 31).

PMID- 22380501
TI  - A commentary on a decrease in consumption of selective COX-2 inhibitors (coxibs)
      Comparison between Slovakia and Nordic countries.
AB  - PURPOSE: The aim of our work was to analyze utilization patterns in Slovakia and
      Nordic countries and to determine coxib risk perception among medical
      professionals. METHODS: The consumption of coxibs in Slovakia during 1999-2009
      was analyzed. Data were obtained from the State Institute for Drug Control in SR.
      Obtained results were compared to data based on annual health statistics in
      Denmark, Finland and Norway. General Practitioners were asked on a perceived
      risk. RESULTS: We observed an increase of consumption in first years, followed
      with a marked decrease after year 2004. Slovak consumption was very small. Coxibs
      represented in Slovakia only a small part of totally prescribed non-steroidal
      anti-inflammatory drugs. They constituted only 1.44 % in the year 2003, whereas
      in Norway 41.2 %. 14 % of respondents (n=570) marked coxibs to be the safest
      analgesic drug. CONCLUSION: Published data show that consumption of coxibs
      (rofecoxib was linked with serious thrombotic cardiovascular adverse effect) fall
      down markedly. Consumption data from 1999 until 2009 from Slovakia and three
      Nordic countries showed significant differences (p<0.001). During the observed
      period, the utilization of coxibs in Slovakia was very small - a possible
      explanation is new drug, higher prize, doctor's habits (Tab. 2, Fig. 1, Ref. 11).

PMID- 22380502
TI  - Malign peritoneal mesothelioma with nephrotic syndrome.
AB  - Nephrotic syndrome may occur in malignancies like Hodgkin Disease and other solid
      tumors due to glomerulonephritis, amyloidosis or other causes. However, it is
      rare in peritoneal mesothelioma. We report a 42-year old female patient with
      peritoneal mesothelioma and nephrotic syndrome together with a review of
      literature (Tab. 1, Fig. 3, Ref. 7).

PMID- 22380503
TI  - Multiple relapses in extramedullary localization of acute lymphoblastic leukemia.
AB  - Extramedullary relapses of acute lymphoblastic leukemia in children and young
      adults are rare and in most cases are usually related to the central nervous
      system or testes. We describe a case of a 25-year-old man with an acute
      lymphoblastic leukemia with multiple extramedullary relapses in the testes,
      gallbladder, breast, parotid gland and eye at various times (Fig. 5, Ref. 21).

PMID- 22380504
TI  - Primary hydatid cyst in an unexpected localization.
AB  - Echinococcal disease remains a problem within some endemic areas. It usually
      involves the liver and lungs, but any other organ can potentially be involved.
      Soft tissue hydatid disease without liver and lung involvement was reported in
      2.3 % of patients. This paper presents a case of 35-year-old male patient who was
      referred to our department with a 9x9x6cm hydatid cyst at psoas muscle. The
      rarity of the musculoskeletal disease renders the decision making on the
      favorable treatment quite difficult. Conservative treatment, complete excision
      and simple drainage have all been suggested as adequate. We advocate total en
      bloc excision whenever possible (Fig. 2, Ref. 4).

PMID- 22380505
TI  - Brown fat tissue - a potential target to combat obesity.
AB  - From the global population perspective, the epidemic of "globesity" (more than
      one billion adults being overweight) represents one of the largest public health
      problems (1). Traditional reasoning related to the dysbalance between caloric
      intake and energy expenditure does not provide a satisfying explanation for a
      complexfailure to combat obesity. The brown adipose tisue (BAT) has a unique
      chemical structure and a specific metabolic role. A potential preventive co
      factor is thermogenesis. BAT has the ability to dissipate energy byproducing
      heat, rather than storing energy as triglycerides. The cells of the white adipose
      tissue (WAT) contain one large globule of triglycerides which displaces the cell
      nucleus and other cell organelles excentrically, to the cell periphery. BAT
      contains numerous smaller droplets of triglycerides, much higher number of
      mitochondria and a specific uncoupling protein 1 or thermogenin. This specialized
      protein uncouples ATP production from mitochondrial respiration and converts
      energy into heat. Using sophisticated diagnostic techniques (e.g. imaging
      combination of positron-emisson tomography and computed tomography), scientists
      confirmed the importance of BAT not only in the newborn but also in adults who
      were found to possess considerable body stores of BAT.The highest proportion of
      BAT has been detected in lean individuals. As the body mass increases, BAT
      proportionately drops. Data both from animal and human studies suggest that BAT
      and mitochondrial uncoupling can be targeted for interventions to prevent and
      treat obesity. Melatonin and arginine have been proposed as possible
      interventional tools. The scientific world eagerly awaits further advanced
      studies to document possible metabolic and pharmacologic interventions, using BAT
      as a primary target to prevent and manage obesity (Fig. 5, Ref. 41).

PMID- 22380506
TI  - The mucin MUC16 (CA125) binds to NK cells and monocytes from peripheral blood of
      women with healthy pregnancy and preeclampsia.
AB  - PROBLEM: MUC16 (CA125) released from ovarian tumors binds to NK cells and
      monocytes via the inhibitory receptor Siglec-9. Here, we investigate whether
      MUC16 also binds to circulating immune cells during pregnancy and in women with
      preeclampsia. METHOD OF STUDY: MUC16 binding was monitored by flow cytometry and
      immunoprecipitation, and RT-PCR was used to monitor indigenous expression in
      immune cells. Serum CA125 levels were measured by a clinical assay. RESULTS:
      MUC16 was equally distributed on Siglec-9(pos) CD16(pos)/CD56(dim) and
      CD16(neg)/CD56(br) NK cells in the healthy pregnant and preeclampsia groups.
      While serum CA125 levels and number of NK and monocytes were similar, increased
      binding of MUC16 was observed on these immune cells in the preeclampsia cohort as
      compared to the healthy pregnant samples. CONCLUSION: MUC16 binding to NK cells
      and monocytes likely contributes to tolerance of the fetal allograft from
      maternal responses and may also serve as a novel biomarker for preeclampsia.

PMID- 22380508
TI  - Cognitive reserve, cortical plasticity and resistance to Alzheimer's disease.
AB  - There are aspects of the ageing brain and cognition that remain poorly understood
      despite intensive efforts to understand how they are related. Cognitive reserve
      is the concept that has been developed to explain how it is that some elderly
      people with extensive neuropathology associated with dementia show little in the
      way of cognitive decline. Cognitive reserve is intimately related to cortical
      plasticity but this also, as it relates to ageing, remains poorly understood at
      the present time. Despite the shortcomings in understanding, we do have some
      knowledge on which to base efforts to minimise the likelihood of an elderly
      person developing dementia. For some risks the evidence is far from secure, but
      resistance to Alzheimer's disease (AD) appears from epidemiological studies to be
      contributed to by avoiding hypertension in middle life, obesity, depression,
      smoking and diabetes and head injury and by undertaking extended years of
      education, physical exercise, and social and intellectual pursuits in middle and
      late life. Nutritional factors may also promote healthy brain ageing. Resistance
      to AD is also contributed to by genetic factors, particularly apolipoprotein E2,
      but some combinations of other genetic polymorphisms as well. Although multiple
      factors and possible interventions may influence cognitive reserve and
      susceptibility to dementia, much more work is required on the mechanisms of
      action in order to determine which, if any, may improve the clinical and
      epidemiological picture. Understanding of how such factors operate may lead to
      new initiatives to keep the elderly population in the 21st century able to lead
      active and fulfilling lives.

PMID- 22380509
TI  - Detection of Vibrio parahaemolyticus in shellfish using polymerase chain reaction
      enzyme-linked immunosorbent assay.
AB  - AIMS: This study evaluated the application of polymerase chain reaction-enzyme
      linked immunosorbent assay (PCR-ELISA) for the detection of Vibrio
      parahaemolyticus in shellfish. METHODS AND RESULTS: The PCRs were selected to
      amplify a species-specific sequence region. In particular, internal tl biotin
      labelled oligonucleotide probe was used to capture the DIG-labelled PCR products.
      Next, the probe PCR product hybrids, immobilized on a streptavidin-coated
      microtiter plate, were detected with peroxidase-conjugated anti-digoxigenin
      antibody (anti-DIG-POD) and the colorimetric peroxidase substrate ABTS [2,2'
      azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] using an ELISA plate reader.
      CONCLUSIONS: The PCR-ELISA system described is a feasible, sensitive method for
      the direct and specific detection of V. parahaemolyticus in shellfish samples.
      Compared with gel-based detection methods, PCR-ELISA in this study increased
      sensitivity by 100-fold for V. parahaemolyticus. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The PCR-ELISA described may be used for potential rapid detection in
      routine shellfish analysis for the seafood industry. The sector requires
      simultaneous large-scale sample screenings to monitor contamination levels in
      processing plants and evaluate the performance of the hazard analysis and
      critical control point (HACCP) system. PCR-ELISA also proved to be economical,
      with a cost of about 9 Euros per sample, and the quick assay taking 8 h to
      complete starting from DNA extraction.

PMID- 22380510
TI  - Electron transport in supported and tethered lipid bilayers modified with
      bioelectroactive molecules.
AB  - Tethered bilayer lipid membranes (tBLMs) are commonly used as model membranes.
      However, in biophysical studies, free-standing membranes ("black" lipid
      membranes) are more realistic models of cellular processes. In this article, we
      discuss the rates of electron transfer in both types of bilayer lipid membranes.
      These BLMs were then modified using two very important mitochondrial membrane
      associated molecules: ubiquinone-10 (UQ10) and alpha-tocopherol (VitE). The
      electron transfer rates in the unmodified films were studied with three redox
      couples, Fe(CN)6(3-/4-), Ru(NH3)6(3+/2+), and NAD+/NADH, using electrochemical
      impedance spectroscopy (EIS) and cyclic voltammetry (CV). The rate of electron
      transfer in the modified films was studied using the biologically relevant
      NAD+/NADH electroactive couple using the same methods. It is shown that when the
      BLMs are modified with only UQ10, it is possible to observe electron transfer.
      However, when the antioxidant VitE is added to the modification, the electron
      transfer provided by UQ10 is inhibited. Following initial studies using CV, a
      comparison of electron transfer theory and data was used to investigate this
      phenomenon in more detail, using EIS data. The standard rate constant caused by
      electron tunneling across the film, k(th)(0), depends on the value of beta used.
      Two different values of the potential independent electron tunneling coefficient,
      beta, were fitted, and it is shown that a beta value half of those usually
      reported in literature (refereed here as beta(app)) gives better agreement
      between the theory and the experimental results. The unmodified films present
      k(th)(0) values on the order of 10(-15) cm s(-1) when beta = 0.72 A(-1) and
      k(th)(0) values on the order of 10(-9) cm s(-1) when beta(app) = 0.38 A(-1). For
      the modified films, the values of k(th)(0) are on the order of 10(-15) cm s(-1)
      when beta = 0.72 A(-1) and 10(-9) cm s(-1) for beta(app) = 0.38 A(-1). The
      experimental electron transfer rate constant, k(app)(0), is on the order of 10(
      8) cm s(-1) for unmodified and modified (with (i) UQ10, (ii) VitE, and (iii) UQ10
      + VitE) films.

PMID- 22380511
TI  - Dynamic modeling of human 5-lipoxygenase-inhibitor interactions helps to discover
      novel inhibitors.
AB  - Human 5-lipoxygenase (5-LOX) is one of the key anti-inflammatory drug targets due
      to its key role in leukotrienes biosynthesis. We have built a model for the
      active conformation of human 5-LOX using comparative modeling, docking of known
      inhibitors, and molecular dynamics simulation. Using this model, novel 5-LOX
      inhibitors were identified by virtual screen. Of the 105 compounds tested in a
      cell-free assay, 30 have IC(50) values less than 100 MUM and 11 less than 10 MUM
      with the strongest inhibition of 620 nM. Compounds 4, 7, and 11 showed strong
      inhibition activity in the human whole blood (HWB) assay with IC(50) values of
      8.6, 9.7, 8.1 MUM, respectively. Moreover, compounds 4 and 7 were also found to
      inhibit microsomal prostaglandin E synthase (mPGES)-1 with micromolar IC(50)
      values, similar to licofelone, a dual functional inhibitor of 5-LOX/mPGES-1. The
      compounds reported here provide new scaffolds for anti-inflammatory drug design.

PMID- 22380512
TI  - Re-evaluating the role of ascorbic acid and phenolic glycosides in ozone
      scavenging in the leaf apoplast of Arabidopsis thaliana L.
AB  - Phenolic glycosides are effective reactive oxygen scavengers and peroxidase
      substrates, suggesting that compounds in addition to ascorbate may have
      functional importance in defence responses against ozone (O(3)), especially in
      the leaf apoplast. The apoplastic concentrations of ascorbic acid (AA) and
      phenolic glycosides in Arabidopsis thaliana L. Col-0 wild-type plants were
      determined following exposure to a range of O(3) concentrations (5, 125 or 175 nL
      L(-1)) in controlled environment chambers. AA in leaf apoplast extracts was
      almost entirely oxidized in all treatments, suggesting that O(3) scavenging by
      direct reactions with reduced AA was very limited. In regard to phenolics, O(3)
      stimulated transcription of numerous phenylpropanoid pathway genes and increased
      the apoplastic concentration of sinapoyl malate. However, modelling of O(3)
      scavenging in the apoplast indicated that sinapoyl malate concentrations were too
      low to be effective protectants. Furthermore, null mutants for sinapoyl esters
      (fah1-7), kaempferol glycosides (tt4-1) and the double mutant (tt4-1/fah1-7) were
      equally sensitive to chronic O(3) as Ler-0 wild-type plants. These results
      indicate that current understanding of O(3) defence schemes deserves reassessment
      as mechanisms other than direct scavenging of O(3) by extracellular AA and
      antioxidant activity of some phenolics may predominate in some plant species.

PMID- 22380513
TI  - Enhancing functional production of a chaperone-dependent lipase in Escherichia
      coli using the dual expression cassette plasmid.
AB  - BACKGROUND: The lipase subfamilies I.1 and I.2 show more than 33% homology in the
      amino acid sequences and most members share another common property that their
      genes are clustered with the secondary genes whose protein products are required
      for folding the lipase into an active conformation and secretion into the culture
      medium. In previous studies, the lipase (LipA) and its chaperone (LipB) from
      Ralstonia sp. M1 were overexpressed in E. coli and the lipase was successfully
      refolded in vitro. The purpose of this study was to enhance the production of the
      active lipase LipA from Ralstonia sp. M1 in the heterologous host E. coli without
      in vitro refolding process, using two-plasmid co-expression systems and dual
      expression cassette plasmid systems. RESULTS: To produce more active lipase from
      Ralstonia sp. M1 in E. coli without in vitro refolding process but with the help
      of overexpression of the chaperone (LipB1 and LipB3 corresponding to 56-aa
      truncated and 26-aa truncated chaperone LipB), six different expression systems
      including 2 two-plasmid co-expression systems (E. coli BL21/pELipABa + pELipB1k
      and BL21/pELipABa + pELipB3k) and 4 dual expression cassette plasmid systems
      (BL21/pELipAB-LipB1a, BL21/pELipAB-LipB3a, BL21/pELipA-LipB1a, and BL21/pELipA
      LipB3a) were constructed. The two-plasmid co-expression systems (E. coli
      BL21/pELipABa + pELipB1k and BL21/pELipABa + pELipB3k) produced the active lipase
      at a level of 4 times as high as the single expression cassette plasmid system E.
      coli BL21/pELipABa did. For the first time, the dual expression cassette plasmid
      systems BL21/pELipAB-LipB1a and BL21/pELipAB-LipB3a yielded 29- and 19-fold
      production of the active lipase in comparison with the single expression cassette
      plasmid system E. coli BL21/pELipABa, respectively. Although the lipase amount
      was equally expressed in all these expression systems (40% of total cellular
      protein) and only a small fraction of the overexpressed lipase was folded in vivo
      into the functional lipase in soluble form whereas the main fraction was still
      inactive in the form of inclusion bodies. Another controversial finding was that
      the dual expression cassette plasmid systems E. coli BL21/pELipAB-LipB1a and E.
      coli/pELipAB-LipB3a secreted the active lipase into the culture medium of 51 and
      29 times as high as the single expression cassette plasmid system E. coli
      pELipABa did, respectively, which has never been reported before. Another
      interesting finding was that the lipase form LipA6xHis (mature lipase fused with
      6* histidine tag) expressed in the dual expression cassette plasmid systems
      (BL21/pELipA-LipB1a and BL21/pELipA-LipB3a) showed no lipase activity although
      the expression level of the lipase and two chaperone forms LipB1 and LipB3 in
      these systems remained as high as that in E. coli BL21/pELipABa + pELipB1k,
      BL21/pELipABa + pELipB3k, BL21/pELipAB-LipB1a, and BL21/pELipAB-LipB3a. The
      addition of Neptune oil or detergents into the LB medium increased the lipase
      production and secretion by up to 94%. CONCLUSIONS: Our findings demonstrated
      that a dual expression cassette plasmid system E. coli could overproduce and
      secrete the active chaperone-dependent lipase (subfamilies I.1 and I.2) in vivo
      and an improved dual expression cassette plasmid system E. coli could be
      potentially applied for industrial-scale production of subfamily I.1 and I.2
      lipases.

PMID- 22380514
TI  - Interleukin-15 suppresses hepatitis B virus replication via IFN-beta production
      in a C57BL/6 mouse model.
AB  - BACKGROUND: Interleukin-15 (IL-15) is a pleiotropic cytokine known to modulate
      both innate and adaptive immunity. It is suggested that IL-15 may play an
      important role in the regulation of immune response to hepatitis B virus (HBV).
      AIMS: We investigated whether IL-15 could modulate the immune response to HBV.
      METHODS: A mouse model for HBV tolerance was established by hydrodynamical
      injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. This HBV-carrier mouse was
      simultaneously hydrodynamically injected with either an IL-15-expression plasmid
      pLIVE-IL-15 or a mock control vector pLIVE-EGFP. The serum levels of HBsAg and
      HBeAg were measured by radioimmunoassay. RESULTS: Hydrodynamic injection of the
      plasmid pLIVE-IL-15 resulted in sustained high level of IL-15 in mouse serum,
      along with the markedly decreased serum HBsAg and HBeAg titres and liver HBV DNA
      levels. IL-15 also induced anti-HBV activity in T cell- and B cell-deficient
      Rag1(-/-)  mice. Interestingly, despite an increase in NK cell numbers in both
      spleen and liver of IL-15 treated mice, the anti-HBV effect of IL-15 was neither
      dependent on presence of NK cells nor on production of IFN-gamma. Furthermore, IL
      15 could exert anti-HBV function independent of the common IL-2gamma(c) R.
      Lastly, we found that IFN-beta expression in the liver and serum was
      significantly up-regulated by liver expression of IL-15, and blockade of IFN-beta
      function abrogated the anti-HBV activity of IL-15. CONCLUSIONS: Liver over
      expression of IL-15 may suppress HBV replication in an IFN-beta-dependent manner.

PMID- 22380516
TI  - G-quadruplex based probes for visual detection and sensing.
AB  - Recent advances in colorimetric biosensing have led to rapid methods for target
      detection, potentially leading to applications on-site, at the point-of-need.
      This review focuses on one such platform, the G-quadruplex-hemin based DNAzymes,
      which exhibit peroxidase- like activity. Since their discovery in the late 1990s,
      various approaches have been adopted in applying the unique catalytic properties
      of these DNAzymes to detecting nucleic acids, proteins, metal ions and other
      ligands, through the oxidation of substrate pre-cursors into colored products. G
      quadruplex based DNAzymes act as modular units of G-rich DNA sequences, and hence
      can be synthesized cheaply and conveniently using routine oligonucleotide
      synthesis. Herein, we discuss the various strategies that have been developed to
      exploit this class of DNAzymes as candidate probes for optical detection and
      sensing, for a variety of chemical and biological targets.

PMID- 22380515
TI  - Inheritance and memory of stress-induced epigenome change: roles played by the
      ATF-2 family of transcription factors.
AB  - Data on the inheritance-of-stress effect have been accumulating and some
      mechanistic insights, such as epigenetic regulation, have also been suggested. In
      particular, the modern view of Lamarckian inheritance appears to be affected by
      the finding that stress-induced epigenetic changes can be inherited. This review
      summarizes the current data on the inheritance of stress effect and possible
      mechanisms involved in this process. In particular, we focus on the stress
      induced epigenetic changes mediated by the ATF-2 family of transcription factors.

PMID- 22380517
TI  - G-quadruplex as signal transducer for biorecognition events.
AB  - G-rich nucleic acid oligomers can form G-quadruplexes built by G-tetrads stacked
      upon each other. The basic building block of the G-quadruplexes is similar, but
      the formation of different quadruplex structures is highly responsive to the
      strand stoichiometry, strand orientation, guanine glycosidic torsion angle,
      connecting loops, and the metal coordination. Because of its structural
      variations and different functions, G-quadruplex applied in biorecognition events
      can function as a versatile signaling component. A variety of strategies that
      incorporate G-quadruplex have also been reported. In this review, we mainly
      discuss G-quadruplex as signal transducer from the following aspects for
      biorecognition events: analyte-induced G-quadruplex reconfiguration and
      fluorescence enhancement of small ligand; analyte-induced G-quadruplex
      reconstruction and formation of DNAzyme; Stimulus-responsive G-quadruplex
      refolding and manipulation of electron transfer; Stimulus-responsive G-quadruplex
      and its combination with nanopore systems; Small ligand-responsive G-quadruplex
      stabilization for drug screening; Nanomaterial-reponsive G-quadruplex
      reformation; Target-triggered continuous formation of G-quadruplex by DNA
      nanomachine. We have comprehensively described the recent progress in our labs
      and others. Undoubtedly, bioanalytical technology and nanotechnology based on G
      quadruplex will continue to grow, leading to develop new diagnostics,
      therapeutics and drug development.

PMID- 22380519
TI  - Risk of second cancers after the diagnosis of non-melanoma skin cancer in Korean
      patients.
AB  - Individuals with a personal history of non-melanoma skin cancer (NMSC) are known
      to have an increased risk of subsequent cancers. However, most of the studies
      regarding this fact were done on Caucasian populations. We investigated whether
      Korean patients with NMSC have an increased risk of developing second cancers
      compared to the general Korean population. Five hundred and thirty-two patients
      diagnosed with NMSC at the Department of Dermatology of Yonsei University Health
      System from 1999 to 2008 were assessed for development of second cancers. The
      overall second cancer incidence was increased among patients diagnosed with NMSC
      compared with the general population in Korea: 37 second cancer total
      (standardized incidence ratio [SIR] 1.38, 95% confidence interval [CI] 1.10
      1.90); 23 second cancers in males (SIR 4.24, 95% CI 2.69-6.36); and 14 second
      cancers in females (SIR 2.28, 95% CI 1.25-3.83). There were significantly
      increased incidence ratios for NMSC (eight second cancers [SIR 9.52, 95% CI 4.11
      18.77]), bladder cancer (four second cancers [SIR 4.21, 95% CI 1.15-10.78]) and
      nasopharyngeal cancer (one second cancer [SIR 20.00, 95% CI: 1.51-25.33]). Korean
      patients diagnosed with NMSC had more second cancers, particularly other skin
      cancers. This study provides additional evidence that NMSC may be a clinically
      significant and substantial risk factor for second cancers even in a Korean
      population, in which the incidence of NMSC is much lower than Caucasians.

PMID- 22380518
TI  - Heterocyclic dications as a new class of telomeric G-quadruplex targeting agents.
AB  - Small molecules that can induce and stabilize G-quadruplex DNA structures
      represent a novel approach for anti-cancer and anti-parasitic therapy and
      extensive efforts have been directed towards discovering lead compounds that are
      capable of stabilizing quadruplexes. The purpose of this study is to explore
      conformational modifications in a series of heterocyclic dications to discover
      structural motifs that can selectively bind and stabilize specific G
      quadruplexes, such as those present in the human telomere. The G-quadruplex has
      various potential recognition sites for small molecules; however, the primary
      interaction site of most of these ligands is the terminal tetrads. Similar to
      duplex-DNA groove recognition, quadruplex groove recognition by small molecules
      offers the potential for enhanced selectivity that can be developed into a viable
      therapeutic strategy. The compounds investigated were selected based on
      preliminary studies with DB832, a bifuryl-phenyl diamidine with a unique telomere
      interaction. This compound provides a paradigm that can help in understanding the
      optimum compound-DNA interactions that lead to quadruplex groove recognition. DNA
      recognition by the DB832 derivatives was investigated by biophysical experiments
      such as thermal melting, circular dichroism, mass spectrometry and NMR.
      Biological studies were also performed to complement the biophysical data. The
      results suggest a complex binding mechanism which involves the recognition of
      grooves for some ligands as well as stacking at the terminal tetrads of the human
      telomeric G-quadruplex for most of the ligands. These molecules represent an
      excellent starting point for further SAR analysis for diverse modes of quadruplex
      recognition and subsequent structure optimization for drug development.

PMID- 22380520
TI  - Bullied by peers in childhood and borderline personality symptoms at 11 years of
      age: a prospective study.
AB  - BACKGROUND: Abuse by adults has been reported as a potent predictor of borderline
      personality disorder (BPD). Unclear is whether victimisation by peers increases
      the risk of borderline personality symptoms. METHOD: The Avon Longitudinal Study
      of Parents and Children (ALSPAC) prospective, longitudinal observation study of
      6050 mothers and their children. Child bullying was measured by self-report and
      mother and teacher report between 4 and 10 years. Family adversity was assessed
      from pregnancy to 4 years; parenting behaviours from 2 to 7 years, sexual abuse
      from 1.5 to 9 years, and IQ and DSM-IV axis I diagnoses at 7 to 8 years. Trained
      psychologists interviewed children at 11.8 years to ascertain DSM-IV BPD symptoms
      (five or more). RESULTS: Accounting for known confounders, victims of peer
      bullying had an increased risk of BPD symptoms according to self-report (OR,
      2.82; 95% CI, 2.13-3.72); mother report (OR, 2.43; 95% CI, 1.86-3.16); and
      teacher report (OR, 1.95; 95% CI, 1.34-2.83). Children who reported being
      chronically bullied (OR, 5.44; 95% CI, 3.86-7.66) or experienced combined
      relational and overt victimisation (OR, 7.10; 95% CI, 4.79-10.51) had highly
      increased odds of developing BPD symptoms. Children exposed to chronic
      victimisation according to mother report were also at heightened risk of
      developing BPD symptoms (OR, 3.24; 95% CI, 2.24-4.68). CONCLUSIONS: Intentional
      harm inflicted by peers is a precursor or marker on the trajectory towards the
      development of BPD symptoms in childhood. Clinicians should be adequately trained
      to deal with, and ask users of mental health services routinely about, adverse
      experiences with peers.

PMID- 22380521
TI  - Invariant natural killer T cells infiltrate intestinal allografts undergoing
      acute cellular rejection.
AB  - Immunological responses in human intestinal allografts are poorly understood and
      accurate diagnosis of acute cellular rejection remains difficult. Here, human
      intestinal allografts were analyzed by multi-color quantitative fluorescent
      immunohistochemical morphometry in order to monitor the clinical course of
      rejection. Morphometry gave two-dimensional plots based on size and circularity,
      and identified phenotypes of individual cells infiltrating the allograft by
      fluorescent staining. Using this method, invariant TCRValpha24(+) NKT (iNKT)
      cells were observed in the intestinal allograft during rejection. Because these
      were not identified in the normal donor intestine before surgery, this finding
      was considered to be a signature of acute cellular rejection of the intestinal
      allograft. Infiltrating iNKT cells released IL-4 and IL-5, Th2-related cytokines
      that antagonize the Th1 responses that induce acute cellular rejection.
      Histological observation suggested eosinophilic enteritis in the mucosa with
      elevation of IL-4 and IL-5. In conclusion, iNKT cells were recruited to the
      intestine; however, because higher levels of IL-4 and IL-5 may contribute to
      eosinophilic enteritis, timely steroid administration is recommended for
      allograft injury due to enteritis, as well as acute cellular rejection.

PMID- 22380522
TI  - Comparison of a rational vs. high throughput approach for rapid salt screening
      and selection.
AB  - In recent years, high throughput (HT) screening has become the most widely used
      approach for early phase salt screening and selection in a drug
      discovery/development setting. The purpose of this study was to compare a
      rational approach for salt screening and selection to those results previously
      generated using a HT approach. The rational approach involved a much smaller
      number of initial trials (one salt synthesis attempt per counterion) that were
      selected based on a few strategic solubility determinations of the free form
      combined with a theoretical analysis of the ideal solvent solubility conditions
      for salt formation. Salt screening results for sertraline, tamoxifen, and
      trazodone using the rational approach were compared to those previously generated
      by HT screening. The rational approach produced similar results to HT screening,
      including identification of the commercially chosen salt forms, but with a
      fraction of the crystallization attempts. Moreover, the rational approach
      provided enough solid from the very initial crystallization of a salt for more
      thorough and reliable solid-state characterization and thus rapid decision
      making. The crystallization techniques used in the rational approach mimic larger
      scale process crystallization, allowing smoother technical transfer of the
      selected salt to the process chemist.

PMID- 22380524
TI  - Glucose tolerance in women 24 h postpartum is related to blood pressure,
      anthropometric data, and adipokine serum levels.
AB  - OBJECTIVES: To characterize glucose tolerance and adipokine serum levels in a
      cohort of women shortly after delivery. STUDY DESIGN: A study population of
      healthy pregnant women (n = 65) was invited to undergo a standardized oral
      glucose tolerance test within 24 h after delivery at the University Hospital of
      Leipzig. As controls, 30 nonpregnant healthy, lean women were studied. Glucose,
      insulin, proinsulin, c-peptide, leptin, adiponectin, and soluble leptin receptor
      levels were compared in cases and controls by using the Mann-Whitney U two-sample
      statistics and correlation according to Spearman. RESULTS: As compared to normal
      glucose tolerant (NGT) women postpartum, fasting c-peptide levels were
      significantly higher (NGT mothers = 0.23 nmol/L, controls: 0.49 nmol/L, p <
      0.001), whereas proinsulin serum levels were significantly lower in nonpregnant
      controls (NGT mothers = 1.37 pmol/L, controls = 1.00 pmol/L, p = 0.05).
      Considering fasting adiponectin values, postpartum adiponectin was significantly
      decreased compared with controls (NGT mothers = 6.9 MUg/L, controls = 8.9 MUg/L,
      p = 0.05). Fasting serum levels of leptin (NGT mothers = 17 ng/mL, controls =
      10.6 ng/mL, p < 0.009) and soluble leptin receptor (NGT mothers = 34.4 ng/mL,
      controls = 17.7 ng/mL, p < 0.001) were increased postpartum. CONCLUSION: We found
      significantly lower adiponectin and higher leptin sera levels in women postpartum
      as compared to nonpregnant women. In addition, adipokine serum levels shortly
      after delivery were related to parameters of adiposity and glucose tolerance. We
      hypothesize that women in the post-delivery period exhibit biochemical features
      resembling metabolic syndrome, impaired glucose tolerance, and derangement of the
      adipokine system.

PMID- 22380523
TI  - Recent progress in West Nile virus diagnosis and vaccination.
AB  - West Nile virus (WNV) is a positive-stranded RNA virus belonging to the
      Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus
      and pestivirus). Among these viruses, there are several globally relevant human
      pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus
      (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as
      tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid
      1990s, outbreaks of WN fever and encephalitis have occurred throughout the world
      and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and
      the Unites States. This review describes the molecular virology, epidemiology,
      pathogenesis, and highlights recent progress regarding diagnosis and vaccination
      against WNV infections.

PMID- 22380525
TI  - Effect of low temperature on chlorophyll biosynthesis in albinism line of wheat
      (Triticum aestivum) FA85.
AB  - The 'stage albinism line of winter wheat' FA85 exhibits a severe block in
      chlorophyll (Chl) biosynthesis with prolonged low-temperature treatment. The
      correlations between leaf color and low temperature provide more comprehensive
      understanding of low temperature as an environmental signal that regulate the
      metabolic changes in the entire Chl-synthesizing pathway. In this study, we
      investigated differences in Chl biosynthesis between leaves of Aibian1 and FA85
      by measuring their Chl precursors and heme content, transcripts for key genes of
      Chl biosynthesis and key enzyme activities. With prolonged low-temperature
      treatment, the Chl content gradually decreased, but Chl precursors, including
      protoporphyrin IX, Mg-protoporphyrin IX and protochlorophyllide (Pchlide),
      simultaneously accumulated. Parallel to the decline in Chl content, the
      protoporphyrin IX distribution toward Chl synthesis was less than that in heme
      synthesis in the leaves of FA85. Corresponding to the change of protoporphyrin IX
      distribution, the relative changes in magnesium chelatase (EC 6.6.1.1) and
      ferrochelatase (EC 4.99.1.1) activities in the leaves of FA85 also indirectly
      reflected channeling of the metabolic flow into heme rather than Chl. A drastic
      loss in the transcripts for Pchlide oxidoreductase (EC 1.3.1.33) and Chl synthase
      (EC 2.5.1.62) accounted for a decrease in the metabolic flux and the re-direction
      of metabolites. The high-level accumulations of Chl precursors and traces of Chl
      in the leaves of FA85 suggest that a severe block between the steps from Pchlide
      to Chl formation during Chl biosynthesis is partially derived from the
      transcriptional downregulation of Pchlide oxidoreductase and Chl synthase.

PMID- 22380526
TI  - Detection of adenosine triphosphate with an aptamer biosensor based on surface
      enhanced Raman scattering.
AB  - A simple, ultrasensitive, highly selective, and reagent-free aptamer-based
      biosensor has been developed for quantitative detection of adenosine triphosphate
      (ATP) using surface-enhanced Raman scattering (SERS). The sensor contains a SERS
      probe made of gold nanostar@Raman label@SiO(2) core-shell nanoparticles in which
      the Raman label (malachite green isothiocyanate, MGITC) molecules are sandwiched
      between a gold nanostar core and a thin silica shell. Such a SERS probe brings
      enhanced signal and low background fluorescence, shows good water-solubility and
      stability, and exhibits no sign of photobleaching. The aptamer labeled with the
      SERS probe is designed to hybridize with the cDNA on a gold film to form a rigid
      duplex DNA. In the presence of ATP, the interaction between ATP and the aptamer
      results in the dissociation of the duplex DNA structure and thereby removal of
      the SERS probe from the gold film, reducing the Raman signal. The response of the
      SERS biosensor varies linearly with the logarithmic ATP concentration up to 2.0
      nM with a limit of detection of 12.4 pM. Our work has provided an effective
      method for detection of small molecules with SERS.

PMID- 22380527
TI  - Controlling soot formation with filtered EGR for diesel and biodiesel fuelled
      engines.
AB  - Although exhaust gas recirculation (EGR) is an effective strategy for controlling
      the levels of nitrogen oxides (NO(X)) emitted from a diesel engine, the full
      potential of EGR in NO(X)/PM trade-off and engine performance (i.e., fuel
      economy) has not fully been exploited. Significant work into the cause and
      control of particulate matter (PM) has been made over the past decade with new
      cleaner fuels and after-treatment devices emerging to comply with the current and
      forthcoming emission regulations. In earlier work, we demonstrated that engine
      operation with oxygenated fuels (e.g., biodiesel) reduces the PM emissions and
      extends the engine tolerance to EGR before it reaches smoke-limited conditions.
      The same result has also been reported when high cetane number fuels such as gas
      to-liquid (GTL) are used. To further our understanding of the relationship
      between EGR and PM formation, a diesel particulate filter (DPF) was integrated
      into the EGR loop to filter the recirculated soot particulates. The control of
      the soot recirculation penalty through filtered EGR (FEGR) resulted in a 50%
      engine-out soot reduction, thus showing the possibility of extending the maximum
      EGR limit or being able to run at the same level of EGR with an improved
      NO(X)/soot trade-off.

PMID- 22380528
TI  - In situ polymerization of polyaniline in wood veneers.
AB  - The present study describes the possibility to polymerize aniline within wood
      veneers to obtain a semi-conducting material with solid wood acting as the base
      template. It was determined that it is possible to synthesize the intrinsically
      conductive polymer (ICP) polyaniline in situ within the wood structure of
      Southern yellow pine veneers, combining the strength of the natural wood
      structure with the conductivity of the impregnated polymer. It was found that
      polyaniline is uniformly dispersed within the wood structure by light microscopy
      and FT-IR imaging. A weight percent gain in the range of 3-12 wt % was obtained
      with a preferential formation in the wood structure and cell wall, rather than in
      the lumen. The modified wood was found to be less hydrophilic with the addition
      of phosphate doped polyaniline as observed by equilibrium water swelling studies.
      While wood itself is insulating, the modified veneers had conductivities of 1 *
      10(-4) to 1 * 10(-9) S cm(-1), demonstrating the ability to tune the conductivity
      and allowing for materials with a wide range of applications, from anti-static to
      charge-dispersing materials. Furthermore, the modified veneers had lower total
      and peak heat releases, as determined by cone calorimetry, because of the char
      properties of the ICP. This is of interest if these materials are to be used in
      building and furniture applications where flame retardance is of importance.

PMID- 22380529
TI  - Randomised clinical trial: the safety and efficacy of long-acting octreotide in
      patients with portal hypertension.
AB  - BACKGROUND: It remains unclear whether a long-acting preparation of octreotide
      (Sandostatin LAR) can be safely used for portal hypertension in patients with
      compensated cirrhosis. AIM: To determine the safety and efficacy of LAR among
      patients with Child Pugh Class A or B cirrhosis and small oesophageal varices.
      METHODS: A randomised, double-blind, placebo-controlled study was conducted in 39
      patients with cirrhosis and small oesophageal varices. Safety was based on
      frequency and severity of adverse events. Efficacy was determined by hepatic vein
      pressure gradient (HVPG) measured at baseline and day 84 following administration
      of LAR 10 mg (n = 15), 30 mg (n = 10) or saline (n = 14). Fasting and
      postprandial portal blood flow (PBF), superior mesenteric artery pulsatility
      index (SMA-PI), glucagon and octreotide levels were measured. An intention-to
      treat analysis was performed. RESULTS: Four patients in the LAR 30 group (40%)
      withdrew from the study due to serious adverse events. No patient in the LAR 10
      or control group had serious adverse events. There was no statistically
      significant decrease between HVPG at day 84 and baseline with LAR 30 mg (11.8 +/-
      2.3 mmHg vs. 14.1 +/- 3.2), LAR 10 mg (15.3 +/- 4.8 mmHg vs. 15.1 +/- 3.8), or
      saline (13.3 +/- 3.8 mmHg vs. 15.1 +/- 4.3) (P = 0.26). Neither PBF, SMA-PI nor
      plasma glucagon levels were significantly decreased from baseline (P = 0.56).
      CONCLUSIONS: The absence of significant haemodynamic benefit, as well as the high
      frequency of severe adverse events associated with use of LAR, do not support the
      use of this agent in the treatment of portal hypertension.

PMID- 22380530
TI  - Determining the energy landscape of proteins by a fast isotope exchange NMR
      approach.
AB  - We present a new and efficient NMR method, BLUU-Tramp (Biophysics Laboratory
      University of Udine temperature ramp), for the collection of hydrogen-deuterium
      exchange experiments as a function of time and temperature for small and medium
      sized proteins. Exchange rates can be determined to extract the underlying
      thermodynamic equilibrium or kinetic parameters by sampling hundreds of points
      over a virtually continuous temperature ramp. Data are acquired in a single
      experimental session that lasts some 20-60 h, depending on the thermal stability
      of the protein. Subsequent analysis provides a complete thermodynamic description
      of the protein energy landscape. The global thermal unfolding process and the
      partial or local structure opening events can be fully determined at the single
      residue resolution level. The proposed approach is shown to work successfully
      with the amyloidogenic protein beta(2)-microglobulin. With (15)N-labeling, the
      unfolding landscape of a protein can also be studied in the presence of other
      unlabeled proteins and, in general, with ligands or cosolutes or in physiological
      environments.

PMID- 22380531
TI  - No evidence for evolution of protease inhibitor resistance from standard
      genotyping, after three years of treatment with darunavir/ritonavir, with or
      without nucleoside analogues.

PMID- 22380532
TI  - Primary adenomyoma of the fallopian tube mimicking tubal malignant tumor.
AB  - We report a rare case of adenomyoma localized only in the left fallopian tube
      mimicking tubal malignant tumor. A 45-year-old woman presented with mild pelvic
      pain, dysmenorrhea and left adnexal mass. Magnetic resonance imaging showed a
      solid tumor, suspected primary cancer of the fallopian tube, and serum
      carbohydrate antigen 125 was elevated to 72 U/mL (normal; 0-35). At surgery, the
      tumor was revealed as a left fallopian tube tumor without torsion. Postoperative
      histopathology showed that the tumor included bundle-like growing non-atypical
      leiomyoma cells and ectopic normal endometrium accompanied with endometrial
      stroma and we diagnosed primary adenomyoma of the left fallopian tube. Adenomyoma
      localized only in the fallopian tube is a rare entity and it can occur only in
      the fallopian tube.

PMID- 22380533
TI  - Isolation and molecular characterization of Candida africana from Jos, Nigeria.
AB  - During a survey of the prevalence of Candida spp. in Jos, Plateau State, Nigeria,
      two atypical C. albicans isolates were recovered. These two yeasts were germ tube
      positive, chlamydospore-negative and gave a green color on CHROMagar Candida.
      Molecular analysis performed by amplification of the hwp1 gene showed that these
      two isolates belonged to C. africana, a newly proposed Candida species closely
      related to C. albicans. Based on the presence or absence of an intron in DNA
      sequences encoding rRNA, the two C. africana, including all C. albicans isolates
      examined, were found to belong to genotype A and no other genotypes or species
      such as C. dubliniensis were found. To our knowledge, this is the first isolation
      of C. africana in Nigeria.

PMID- 22380535
TI  - Clinical examination or whole-body magnetic resonance imaging: the Holy Grail of
      spondyloarthritis imaging.

PMID- 22380534
TI  - Direct induction of apoptosis using an optimal mitochondrially targeted p53.
AB  - Targeting the tumor suppressor p53 to the mitochondria triggers a rapid apoptotic
      response as efficiently as transcription-dependent p53. (1, 2)  p53 forms a
      complex with the antiapoptotic Bcl-XL, which leads to Bak and Bax oligomerization
      resulting in apoptosis via mitochondrial outer membrane permeabilization. (3, 4) 
      Although p53 performs its main role in the mitochondrial outer membrane, it also
      interacts with different proteins in the mitochondrial inner membrane and matrix.
      (5, 6)  To further investigate mitochondrial activity of p53, EGFP-p53 was fused
      to different mitochondrial targeting signals (MTSs) directing it to the
      mitochondrial outer membrane ("XL-MTS" from Bcl-XL; "TOM-MTS" from TOM20), the
      inner membrane ("CCO-MTS" from cytochrome c oxidase), or matrix ("OTC-MTS" from
      ornithine transcarbamylase). Fluorescence microscopy and a p53 reporter dual
      luciferase assay demonstrated that fusing MTSs to p53 increased mitochondrial
      localization and nuclear exclusion depending on which MTS was used. To examine if
      the MTSs initiate mitochondrial damage, we fused each individual MTS to EGFP (a
      nontoxic protein) as negative controls. We performed caspase-9, TUNEL, annexin-V,
      and 7-AAD apoptosis assays on T47D breast cancer cells transfected with
      mitochondrial constructs. Except for EGFP-XL, apoptotic potential was observed in
      all MTS-EGFP-p53 and MTS-EGFP constructs. In addition, EGFP-p53-XL showed the
      greatest significant increase in programmed cell death compared to its nontoxic
      MTS control (EGFP-XL). The apoptotic mechanism for each construct was further
      investigated using pifithrin-alpha (an inhibitor of p53 transcriptional
      activity), pifithrin-MU (a small molecule that reduces binding of p53 to Bcl-2
      and Bcl-XL), and overexpressing the antiapoptotic Bcl-XL. Unlike the MTSs from
      TOM, CCO, and OTC, which showed different apoptotic mechanisms, we conclude that
      p53 fused to the MTS from Bcl-XL performs its apoptotic potential exclusively
      through the p53/Bcl-XL specific pathway.

PMID- 22380536
TI  - Multiscale simulations of the antimicrobial peptide maculatin 1.1: water
      permeation through disordered aggregates.
AB  - The antimicrobial peptide maculatin 1.1 (M1.1) is an amphipathic alpha-helix that
      permeabilizes lipid bilayers. In coarse-grained molecular dynamics (CG MD)
      simulations, M1.1 has previously been shown to form membrane-spanning aggregates
      in DPPC bilayers. In this study, a simple multiscale methodology has been applied
      to allow sampling of important regions of the free energy surface at higher
      resolution. Thus, by back-converting the CG configurations to atomistic
      representations, it is shown that water is able to permeate through the M1.1
      aggregates. Investigation of aggregate stoichiometry shows that at least six
      peptides are required for water permeation. The aggregates are dynamically
      disordered structures, and water flux occurs through irregular, fluctuating
      channels. The results are discussed in relation to experimental data and other
      simulations of antimicrobial peptides.

PMID- 22380537
TI  - Differential effects of dairy snacks on appetite, but not overall energy intake.
AB  - Dietary regulation of appetite may contribute to the prevention and management of
      excess body weight. The present study examined the effect of consumption of
      individual dairy products as snacks on appetite and subsequent ad libitum lunch
      energy intake. In a randomised cross-over trial, forty overweight men (age 32 (sd
      9) years; BMI 27 (sd 2) kg/m2) attended four sessions 1 week apart and received
      three isoenergetic (841 kJ) and isovolumetric (410 ml) servings of dairy snacks
      or water (control) 120 min after breakfast. Appetite profile was determined
      throughout the morning and ad libitum energy intake was assessed 90 min after the
      intake of snacks. Concentrations of amino acids, glucose, insulin, ghrelin and
      peptide tyrosine tyrosine were measured at baseline (0 min) and 80 min after the
      intake of snacks. Although the results showed that yogurt had the greatest
      suppressive effect on appetite, this could be confounded by the poor sensory
      ratings of yogurt. Hunger rating was 8, 10 and 24 % (P < 0.001) lower after the
      intake of yogurt than cheese, milk and water, respectively. Energy intake was 11,
      9 and 12 % (P < 0.02) lower after the intake of yogurt, cheese and milk,
      respectively, compared with water (4312 (se 226) kJ). Although there was no
      difference in the postprandial responses of hormones, alanine and isoleucine
      concentrations were higher after the intake of yogurt than cheese and milk (P <
      0.05). In conclusion, all dairy snacks reduced appetite and lunch intake compared
      with water. Yogurt had the greatest effect on suppressing subjective appetite
      ratings, but did not affect subsequent food intake compared with milk or cheese.

PMID- 22380538
TI  - Quantifying succulence: a rapid, physiologically meaningful metric of plant water
      storage.
AB  - Quantification of succulence should ideally convey information about
      physiological function and yet also be straightforward to measure. While
      important aspects of succulence and its physiological consequences may be
      quantified using parameters derived from pressure-volume (P-V) curves, this
      technique applied to succulent tissues is difficult, time consuming and generally
      not suitable for large comparative datasets. We performed P-V curves on leaves of
      25 taxa from across Caryophyllales and compared the results with direct measures
      of saturated water content (SWC(meas) ), the ratio of water mass at full
      saturation to tissue dry mass, for the same taxa. SWC(meas) was significantly
      related to relative capacitance, the most physiologically relevant parameter
      describing tissue succulence. We developed a linear model describing SWC(meas) as
      a function of relative capacitance and leaf volume, which is also supported when
      accounting for the phylogenetic relationships among taxa. These results indicate
      that SWC(meas) is a suitable proxy for tissue succulence, and that both cellular
      properties and variation in gross morphology contribute towards a plant's
      relative water storage capacity. Quantifying SWC(meas) across many taxa showing
      variation in tissue succulence will provide a new avenue for exploring the
      evolutionary dynamics of this important ecological adaptation.

PMID- 22380539
TI  - The relationship between osteoclastogenic and anti-osteoclastogenic pro
      inflammatory cytokines differs in human osteoporotic and osteoarthritic bone
      tissues.
AB  - BACKGROUND: Pro-inflammatory cytokines possess osteoclastogenic or anti
      osteoclastogenic activities. They influence osteoclasts directly or via the
      receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL) and
      osteoprotegerin (OPG) system. Recent evidence suggests that inflammation may play
      a role in osteoporosis (OP) and osteoarthritis (OA). We aimed therefore to
      determine whether there is a difference between both groups: first, in the
      expression of the osteoclastogenic and anti-osteoclastogenic cytokines, second,
      in correlation of these cytokines with bone mineral density (BMD) and levels of
      bone turnover markers (BTM) and third, in correlation between the expression of
      these cytokines and osteoclast specific genes and RANK/RANKL/OPG genes. METHODS:
      Human bone samples from 54 age and sex matched patients with OP or OA were
      collected during hip arthroplasty surgery. The expression of 25 genes encoding
      pro-inflammatory cytokines, their receptors, osteoclast specific genes and
      RANK/RANKL/OPG genes was measured using quantitative real-time PCR. Total hip,
      femoral neck and lumbar spine BMD and BTM in blood samples were measured. The
      comparison between OP and OA was assessed using Student's t-test or Mann-Whitney
      U test and correlations between gene expression, BMD and BTM were determined
      using nonparametric correlation. RESULTS: The results demonstrated a higher
      expression of interleukin (IL)-6 and IL-1alpha in OP, and interferon (IFN)-gamma
      in OA (p < 0.0005). Negative correlations of total hip BMD with tumor necrosis
      factor-alpha (TNF-alpha) in OA and with RANKL/RANK in OP were found (p < 0.05).
      Significant correlations with BTM were shown for IL-1alpha and IFN-gamma in OP
      (rho = 0.608 and -0.634) and for TNF-alpha, IL-6 and transforming growth factor
      beta1 (TGF-beta1) in OA (rho = 0.591, -0.521 and 0.636). Results showed OP
      specific negative correlations (IFN-gamma with ITGB3, IFN-beta1 with CTSK,
      tartrate resistant acid phosphatase (TRAP), CALCR, RANK, RANKL, IL-1alpha with
      CTSK, OPG, IL-17A with CALCR) and positive (TGF-beta1 with CTSK, TRAP, RANK), and
      OA specific negative (IL-1alpha with osteoclast associated immunoglobulin-like
      receptor (OSCAR), TNF-alpha with RANK, RANKL, OPG) and positive (IL-6 with RANK,
      RANKL, OPG) correlations. CONCLUSIONS: Our results demonstrate that the
      relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory
      cytokines differs in human OP and OA bone and could present an important factor
      for characteristics of OP and OA bone phenotypes.

PMID- 22380540
TI  - One-step of tryptophan attenuator inactivation and promoter swapping to improve
      the production of L-tryptophan in Escherichia coli.
AB  - BACKGROUND: L-tryptophan is an aromatic amino acid widely used in the food,
      chemical and pharmaceutical industries. In Escherichia coli, L-tryptophan is
      synthesized from phosphoenolpyruvate and erythrose 4-phosphate by enzymes in the
      shikimate pathway and L-tryptophan branch pathway, while L-serine and
      phosphoribosylpyrophosphate are also involved in L-tryptophan synthesis. In order
      to construct a microbial strain for efficient L-tryptophan production from
      glucose, we developed a one step tryptophan attenuator inactivation and promoter
      swapping strategy for metabolic flux optimization after a base strain was
      obtained by overexpressing the tktA, mutated trpE and aroG genes and inactivating
      a series of competitive steps. RESULTS: The engineered E. coli GPT1002 with
      tryptophan attenuator inactivation and tryptophan operon promoter substitution
      exhibited 1.67 ~ 9.29 times higher transcription of tryptophan operon genes than
      the control GPT1001. In addition, this strain accumulated 1.70 g l(-1) L
      tryptophan after 36 h batch cultivation in 300-mL shake flask. Bioreactor
      fermentation experiments showed that GPT1002 could produce 10.15 g l(-1) L
      tryptophan in 48 h. CONCLUSIONS: The one step inactivating and promoter swapping
      is an efficient method for metabolic engineering. This method can also be applied
      in other bacteria.

PMID- 22380541
TI  - Glucocorticoid receptor mediates the effect of progesterone on uterine natural
      killer cells.
AB  - PROBLEM: Uterine natural killer cells (uNK) do not express progesterone receptor,
      but express glucocorticoid receptor (GR). So, we speculate that progesterone may
      regulate uNK cells through a GR-mediated process. METHOD OF STUDY: After mouse NK
      cells were stimulated with CpG with or without IL-12 in the presence or absence
      pre-treatment of progesterone, the effects of progesterone on NK via GR were
      investigated by using RU486 (progesterone receptor and GR antagonist) and CDB
      2914 (progesterone receptor antagonist). The expressions of CD69 and IFN-gamma
      were determined by flow cytometry and qPCR. Phosphorylation of IkappaB and STAT4
      was determined by Western blot. Furthermore, we purified uNK cells from human
      decidual tissues using anti-CD56 microbeads to verify the effect of progesterone
      on uNK via GR. RESULTS: Progesterone suppressed CD69 and IFN-gamma expression of
      mouse spleen NK cells and human uNK cells induced by CpG combined with IL-12. CDB
      2914 had no effect on IFN-gamma expression suppressed by progesterone, while
      RU486 could abolish the inhibitory effect of progesterone. In addition,
      progesterone could decrease the phosphorylation of both STAT4 and IkappaB.
      CONCLUSIONS: In the present study, we first prove that progesterone can regulate
      NK cells via GR. It is valuable for further understanding the role of uNK in
      progesterone regulated gestation process.

PMID- 22380542
TI  - A maxillary mass in a HBV-cirrhotic patient.

PMID- 22380543
TI  - Extending the income inequality hypothesis: ecological results from the 2005 and
      2009 Argentine National Risk Factor Surveys.
AB  - A consensus on income inequality as a social determinant of health is yet to be
      reached. In particular, we know little about the cross-sectional versus lagged
      effect of inequality and the robustness of the relationship to indicators that
      are sensitive to varying parts of the income spectrum. We test these issues with
      data from Argentina's 2005 and 2009 National Risk Factor Surveys. Inequality was
      operationalised at the provincial level with the Gini coefficient and the
      Generalised Entropy (GE) index. Population health was defined as the age
      standardised percentage of adults with poor/fair self-rated health by province.
      Our cross-sectional results indicate a significant relationship between
      inequality (Gini) and poor health (r=0.58, p<0.01) in 2005. Using the GE index, a
      gradient pattern emerges in the correlation, and the r values increase as the
      index becomes sensitive to the top of the distribution. The relationship between
      2005 inequality and 2009 health displays a similar pattern, but with generally
      smaller correlations than the 2005 cross-sectional results. Further advances in
      the income inequality and health literature require new theoretical models to
      account for how inequalities in different parts of the income spectrum may
      influence population health in different ways.

PMID- 22380544
TI  - Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and
      systemic symptoms syndrome induced by cilostazol and carbamazepine.

PMID- 22380545
TI  - Effect of terminated fetal circulation on maternal angiogenic factors in severe
      early preeclampsia.
AB  - BACKGROUND; Although intrauterine presence of the placenta is essential in the
      etiology of preeclampsia (PE), case reports showed that the viability of the
      fetus influences the clinical course of PE and the intensity of the clinical
      symptoms. AIM: We examined the course of angiogenic factors soluble fms-like
      tyrosine kinase-1 receptors (sFlt-1) and placental growth factor (PlGF) in a case
      of severe early PE in week 22 + 1 of gestation, when fetal termination was
      required to stabilize maternal condition. RESULTS: The cessation of the feto
      placental perfusion via fetocide led to a reduction of the maternal sFlt-1
      concentration of 8.3% which was associated with a decline of the sFlt-1/PlGF
      ratio from 405 to 334. Nevertheless, the highest change of the angiogenic factors
      was detected after ejection of the fetus and placenta. CONCLUSIONS: Our
      observations implicate that neither a vital fetus nor an intact feto-placental
      component is an obligatory prerequisite for the angiogenic imbalance that is
      associated with the preeclamptic phenotype.

PMID- 22380546
TI  - Influence of polymers/excipients on development of agglomerated crystals of
      secnidazole by crystallo-co-agglomeration technique to improve processability.
AB  - BACKGROUND: Direct tabletting is a need of Pharmaceutical industries. Poor
      mechanical properties of drug particles require wet granulation which is
      uneconomical, laborious, and tedious. OBJECTIVE: Objective of this work was to
      study influence of various polymers/excipients on formation of directly
      compressible Crystallo-co-agglomerates (CCA) of water soluble drug Secnidazole
      (hydroxy-2-propyl)-1-methyl-2-nitro-5-imidazole), an antimicrobial agent. METHOD:
      Acetone-petroleum ether system was used to develop CCA of drug in the presence of
      polymers/excipients. Clarity of the supernatant was considered an endpoint for
      completion of agglomeration. The prepared CCA were subjected for topographic,
      micromeritic, mechanical, compressional, and drug release properties. RESULTS:
      The process yielded ~92 to 98% wt/wt CCA containing secnidazole with the diameter
      between 0.2 and 0.7 mm. CCA showed excellent flow, packability, compatibility,
      and crushing strength. Heckel plot showed lower sigma(0) and higher tensile
      strength with lower elastic recovery (0.55-1.28%) of CCA. Dissolution profile of
      CCA was improved. Differential scanning calorimetry , fourier transform infra
      red, and x-ray diffractometry results showed absence of drug-excipient
      interaction. DISCUSSION: Matrix beads were generated with uniform dispersion of
      crystallized drug. Excellent flow, packability, and compactability were due to
      sphericity of agglomerates. Higher crushing strength of CCA was an indication of
      good handling qualities. Lower sigma(0), higher tensile strength, and lower
      elastic recovery indicated excellent compressibility of agglomerates. Improvement
      in dissolution profile was due to porous nature of CCA. CONCLUSION: Excipients
      and polymers can play a key role to prepare CCA, an excellent alternative to wet
      granulation process to prepare particles for direct compression.

PMID- 22380547
TI  - Public health, climate, and economic impacts of desulfurizing jet fuel.
AB  - In jurisdictions including the US and the EU ground transportation and marine
      fuels have recently been required to contain lower concentrations of sulfur,
      which has resulted in reduced atmospheric SO(x) emissions. In contrast, the
      maximum sulfur content of aviation fuel has remained unchanged at 3000 ppm
      (although sulfur levels average 600 ppm in practice). We assess the costs and
      benefits of a potential ultra-low sulfur (15 ppm) jet fuel standard ("ULSJ"). We
      estimate that global implementation of ULSJ will cost US$1-4bn per year and
      prevent 900-4000 air quality-related premature mortalities per year. Radiative
      forcing associated with reduction in atmospheric sulfate, nitrate, and ammonium
      loading is estimated at +3.4 mW/m(2) (equivalent to about 1/10th of the warming
      due to CO(2) emissions from aviation) and ULSJ increases life cycle CO(2)
      emissions by approximately 2%. The public health benefits are dominated by the
      reduction in cruise SO(x) emissions, so a key uncertainty is the atmospheric
      modeling of vertical transport of pollution from cruise altitudes to the ground.
      Comparisons of modeled and measured vertical profiles of CO, PAN, O(3), and (7)Be
      indicate that this uncertainty is low relative to uncertainties regarding the
      value of statistical life and the toxicity of fine particulate matter.

PMID- 22380548
TI  - Germ cells and fertilization differences among Japanese flounder Paralichthys
      olivaceus, summer flounder Paralichthys dentatus and their first and second
      generations.
AB  - The morphology of gametes and the fertilization biology of Japanese flounder
      Paralichthys olivaceus (Po), summer flounder Paralichthys dentatus (Pd) and their
      hybrids were examined. Multiple generations (two hybrids: Po?* Pd? (F1) and Pd?*
      Po?; two backcrosses: F1?* Po? and F1?* Pd?) were obtained by artificial
      insemination. Comparison of egg ultrastructure among Po, Pd and F1 showed the
      morphology of micropyle region and the distribution density of pores were species
      specific. There were c. 100-200 accessory openings around the micropyle in Po,
      but not in Pd and F1. The zona radiata thickness and number of parallel bands
      were similar between F1 and Po, which were different from Pd. Comparison of
      spermatozoa ultrastructure revealed a close relationship between Po and Pd.
      Cytologically, the six crosses obeyed normal fertilization and cleavage
      processes, and only one male pronucleus was observed in a fertilized egg,
      indicating a monospermic fertilization pattern. Analysis of the time distribution
      from fertilization to first cleavage revealed an obvious delay at pronucleus
      fusion in the Pd * Po cross. The delay might indicate some cytoplasmic-nuclear
      incompatibility during the process of fertilization.

PMID- 22380549
TI  - Skeletal development and abnormalities of the vertebral column and of the fins in
      hatchery-reared turbot Scophthalmus maximus.
AB  - To describe the skeletal development and abnormalities in turbot Scophthalmus
      maximus, samples were collected every day from hatching to 60 days after hatching
      (DAH). A whole-mount cartilage and bone-staining technique was used. Vertebral
      ontogeny started with the formation of anterior haemal arches at 5.1 mm standard
      length (L(S) ) c. 11 DAH, and was completed by the full attainment of
      parapophyses at 16.9 mm L(S)  c. 31 DAH. Vertebral centra started to develop at
      6.3 mm L(S)  c. 16 DAH and ossification in all centra was visible at 11.0 mm L(S)
      c. 25 DAH. The caudal fin appeared at 5.1 mm L(S)  c. 11 DAH and ossification
      was visible at 20.6 mm L(S)  c. 37 DAH. The onset of dorsal and anal fin elements
      appeared at 5.8 mm L(S)  c. 15 DAH and 6.3 mm L(S)  c. 16 DAH, respectively.
      Ossifications of both dorsal fin and anal fin were visible at 20.6 mm L(S)  c. 37
      DAH. The pectorals were the only fins present before first feeding, their
      ossifications were completed at 23.5 mm L(S)  c. 48 DAH. Pelvic fins began
      forming at 7.2 mm L(S)  c. 19 DAH and calcification of the whole structure was
      visible at 19.8 mm L(S)  c. 36 DAH. In the present study, 24 types of skeletal
      abnormalities were observed. About 51% of individuals presented skeletal
      abnormalities, and the highest occurrence was found in the haemal region of the
      vertebral column. As for each developmental stage, the most common abnormalities
      were in the dorsal fin during early metamorphic period (stage 2), vertebral
      fusion during climax metamorphosis (stage 3) and caudal fin abnormality during
      both late-metamorphic period (stage 4) and post-metamorphic period (stage 5).
      Such research will be useful for early detection of skeletal malformations during
      different growth periods of reared S. maximus.

PMID- 22380550
TI  - Kin and familiarity influence association preferences and aggression in the
      mangrove killifish Kryptolebias marmoratus.
AB  - Association preferences and aggression intensity were investigated in relation to
      kin and familiarity in the self-fertilizing, clonal vertebrate, the mangrove
      killifish Kryptolebias marmoratus. Results indicated that fish preferentially
      associated with and exhibited less intense aggression towards members of their
      own genotype (kin), compared to members of a different genotype (non-kin).
      Furthermore, when fish were presented with stimulus groups of the same genotype
      that were familiar or unfamiliar, fish preferentially associated with and
      exhibited lower aggression intensity directed towards familiar groups. These
      results indicate that this species prefer to associate with both kin and familiar
      individuals and modulate aggression accordingly. These results are discussed with
      reference to the adaptive benefits of kin recognition and preferences for
      familiars, and place results within the context of current knowledge of the
      ecology of K. marmoratus.

PMID- 22380551
TI  - Fishing top predators indirectly affects condition and reproduction in a reef
      fish community.
AB  - To examine the indirect effects of fishing on energy allocation in non-target
      prey species, condition and reproductive potential were measured for five
      representative species (two-spot red snapper Lutjanus bohar, arc-eye hawkfish
      Paracirrhites arcatus, blackbar devil Plectroglyphidodon dickii, bicolour chromis
      Chromis margaritifer and whitecheek surgeonfish Acanthurus nigricans) from three
      reef-fish communities with different levels of fishing and predator abundance in
      the northern Line Islands, central Pacific Ocean. Predator abundance differed by
      five to seven-fold among islands, and despite no clear differences in prey
      abundance, differences in prey condition and reproductive potential among islands
      were found. Body condition (mean body mass adjusted for length) was consistently
      lower at sites with higher predator abundance for three of the four prey species.
      Mean liver mass (adjusted for total body mass), an indicator of energy reserves,
      was also lower at sites with higher predator abundance for three of the prey
      species and the predator. Trends in reproductive potential were less clear. Mean
      gonad mass (adjusted for total body mass) was high where predator abundance was
      high for only one of the three species in which it was measured. Evidence of
      consistently low prey body condition and energy reserves in a diverse suite of
      species at reefs with high predator abundance suggests that fishing may
      indirectly affect non-target prey-fish populations through changes in predation
      and predation risk.

PMID- 22380552
TI  - Multiple functions of a multi-component mating pheromone in sea lamprey
      Petromyzon marinus.
AB  - The role of the C24 sulphate in the mating pheromone component, 7alpha,12alpha,24
      trihydroxy-5alpha-cholan-3-one 24-sulphate (3kPZS), to specifically induce
      upstream movement in ovulated female sea lampreys Petromyzon marinus was
      investigated. 7alpha,12alpha-dihydroxy-5alpha-cholan-3-one 24-oic acid (3kACA), a
      structurally similar bile acid released by spermiated males, but lacking the C24
      sulphate ester, was tested in bioassays at concentrations between 10(-11)  and
      10(-14)  molar (M). 3kACA did not induce upstream movement in females or
      additional reproductive behaviours. In contrast, spermiated male washings induced
      upstream movement, prolonged retention on a nest and induced an array of nesting
      behaviours. Differential extraction and elution by solid-phase extraction resins
      showed that components other than 3kPZS + 3kACA are necessary to retain females
      on nests and induce nest cleaning behaviours. All pheromone components, including
      components in addition to 3kPZS + 3kACA that retain females and induce nest
      cleaning behaviours were released from the anterior region of the males, as had
      been reported for 3kPZS. It is concluded that the sea lamprey male mating
      pheromone has multiple functions and is composed of multiple components.

PMID- 22380553
TI  - Early development of New Zealand hapuku Polyprion oxygeneios eggs and larvae.
AB  - This study describes for the first time the normal development of New Zealand
      hapuku Polyprion oxygeneios embryos and larvae reared from fertilization to 11
      days post-hatch (dph) at a constant temperature. Fertilized eggs were obtained
      from natural spawnings from communally reared captive wild broodstock. Eggs
      averaged 2 mm in diameter and had single or multiple oil globules. Embryos
      developed following the main fish embryological stages and required an average of
      1859.50 degree hours post-fertilization (dhpf) to hatch. The newly hatched larvae
      (4.86 mm mean total length, L(T) ) were undifferentiated, with unpigmented eyes,
      a single and simple alimentary tube and a finfold that covered the entire body.
      Larvae relied on the energy from the yolk-sac reserves until 11 dph (7.33 mm mean
      L(T) ), when yolk-sac reabsorption was almost completed. Some of the major
      developmental stages from hatching to yolk-sac reabsorption were eye pigmentation
      (5 dph), upper jaw formation (7 dph), lower jaw formation (8 dph) and mouth
      opening (8-9 dph). By 9 dph, the digestive system consisted of pancreas, liver,
      primordial stomach, anterior and posterior gut; therefore, P. oxygeneios larvae
      would be capable of feeding on live prey. The developmental, morphological and
      histological data described constitutes essential baseline information on P.
      oxygeneios biology and normal development.

PMID- 22380554
TI  - Gonadal morphogenesis and sex differentiation in the viviparous fish
      Chapalichthys encaustus (Teleostei, Cyprinodontiformes, Goodeidae).
AB  - This study describes the structural and ultrastructural characteristics of
      gonadal sex differentiation and expression of Vasa, a germline marker, in
      different developmental stages of embryos and newborn fry of the barred splitfin
      Chapalichthys encaustus, a viviparous freshwater teleost endemic to Mexico. In
      stage 2 embryos, the gonadal crest was established; gonadal primordia were
      located on the coelomic epithelium, formed by scarce germ and somatic cells. At
      stage 3, the undifferentiated gonad appeared suspended from the mesentery of the
      developing swimbladder and contained a larger number of germ and somatic cells.
      At stages 4 and 5, the gonads had groups of meiotic and non-meiotic germ cells
      surrounded by somatic cells; meiosis was evident from the presence of
      synaptonemal complexes. These stages constituted a transition towards
      differentiation. At stage 6 and at birth, the gonad was morphologically
      differentiated into an ovary or a testis. Ovarian differentiation was revealed by
      the presence of follicles containing meiotic oocytes, and testicular
      differentiation by the development of testicular lobules containing spermatogonia
      in mitotic arrest, surrounded by Sertoli cells. Nuage, electron-dense material
      associated with mitochondria, was observed in germ cells at all gonadal stages.
      The Vasa protein was detected in all of the previously described stages within
      the germ-cell cytoplasm. This is the first report on morphological
      characteristics and expression of the Vasa gene during sexual differentiation in
      viviparous species of the Goodeidae family. Chapalichthys encaustus may serve as
      a model to study processes of sexual differentiation in viviparous fishes and
      teleosts.

PMID- 22380555
TI  - Influences of potential predictor variables on gastric evacuation in Atlantic cod
      Gadus morhua feeding on fish prey: parameterization of a generic model.
AB  - The parameter values of a generic model of gastric evacuation were estimated from
      evacuation data on Atlantic cod Gadus morhua fed meals of four fish prey: herring
      Clupea harengus, sprat Sprattus sprattus, lesser sandeel Ammodytes tobianus and
      dab Limanda limanda. The effects on evacuation of photoperiod and pre
      experimental treatment of prey were also tested. Freshly killed A. tobianus were
      evacuated from the stomach of G. morhua at a rate similar to the value estimated
      from conspecifics kept deep-frozen and subsequently thawed prior to the
      evacuation experiment. The evacuation rate in G. morhua exposed to continuous
      light did not differ from the rate obtained from fish maintained under a 12L:12D
      photoperiod. The evacuation rates estimated from the latter fish in the dark and
      light periods, respectively, were likewise similar. These results indicate that
      the resistance of prey to the digestive processes is not altered significantly by
      the pre-experimental treatment of prey and that there is no diurnal variation per
      se in the rate of evacuation for G. morhua. Therefore, it is believed that the
      present parameterization of the evacuation model should prove especially useful
      for studying the role of G. morhua as a top predator in natural systems.

PMID- 22380556
TI  - Evidence of sustained populations of a small reef fish on artificial structures.
      Does depth affect production on artificial reefs?
AB  - The length frequencies and age structures of resident Pseudanthias rubrizonatus
      (n = 407), a small protogynous serranid, were measured at four isolated
      artificial structures on the continental shelf of north-western Australia between
      June and August 2008, to determine whether these structures supported full
      (complete size and age-structured) populations of this species. The artificial
      structures were located in depths between 82 and 135 m, and growth rates of
      juveniles and adults, and body condition of adults, were compared among
      structures to determine the effect of depth on potential production. All life
      history stages, including recently settled juveniles, females and terminal males,
      of P. rubrizonatus were caught, ranging in standard length (L(s)) from 16.9 to
      96.5 mm. Presumed ages estimated from whole and sectioned otoliths ranged between
      22 days and 5 years, and parameter +/-s.e. estimates of the von Bertalanffy
      growth model were L(infinity) = 152 +/- 34 mm, k = 0.15(+/-0.05) and t(0) = 
      1.15(+/-0.15). Estimated annual growth rates were similar between shallow and
      deep artificial structures; however, otolith lengths and recent growth of
      juveniles differed among individual structures, irrespective of depth. The
      artificial structures therefore sustained full populations of P. rubrizonatus,
      from recently settled juveniles through to adults; however, confirmation of the
      maximum age attainable for the species is required from natural populations.
      Depth placement of artificial reefs may not affect the production of fish species
      with naturally wide depth ranges.

PMID- 22380557
TI  - Cytogenetic mapping of the W chromosome in the genus Leporinus (Teleostei,
      Anostomidae) using a highly repetitive DNA sequence.
AB  - The distribution of the Leporinus elongatus LeSpeI repetitive sequence in other
      Leporinus species was studied in an attempt to elucidate the evolutionary history
      of sex chromosomes in this genus using chromosome fluorescence in situ
      hybridization. The presence of fluorescent signals only in species that have
      differentiated sex chromosomes suggests that this sequence is related to the
      differentiation of sex chromosomes in this genus. Thus, these data will
      contribute to a better understanding of chromosome evolution, especially for sex
      chromosomes, in the Leporinus genus.

PMID- 22380558
TI  - Resilience of inshore, juvenile snapper Pagrus auratus to angling and release.
AB  - This study assessed the mortality of 157 snapper Pagrus auratus (9-29 cm, total
      length, L(T) ) after being conventionally angled and then released into cages
      (along with 48 controls) for 4 days off south-eastern Australia. Fatalities were
      restricted to 12 angled fish (7.6%) and mostly attributed to the ingestion of
      hooks and especially their subsequent removal, which caused substantial blood
      loss and immediate death. Hook ingestion was significantly biased towards smaller
      fish (<21 cm L(T)) and attributed to a lower chance of anglers initially
      detecting these individuals on the line (allowing them to consume more of the
      baits). While mortalities might be reduced in future via (1) choosing terminal
      rigs that promote mouth hooking and (2) cutting the line on any-hook ingested
      fish, the results nevertheless validate releasing unwanted angled inshore
      juvenile P. auratus as a means for managing their exploitation.

PMID- 22380559
TI  - Strong population genetic structure and its management implications in the mud
      carp Cirrhinus molitorella, an indigenous freshwater species subject to an
      aquaculture and culture-based fishery.
AB  - This study investigated population genetic structure and diversity of mud carp
      Cirrhinus molitorella, a species widely used in aquaculture and culture-based
      fisheries in China and Mekong River riparian countries. Seven newly developed and
      one published microsatellite DNA markers were used to analyse samples from six
      wild locations, four hatchery broodstocks and one farmed site from the Mekong,
      Red and Pearl Rivers. Significant genetic structure was detected in C.
      molitorella, with isolation-by-distance being a strong force in the Mekong. Pair
      wise F(ST) , Fisher's exact tests for population differentiation, permutation
      tests and individual-based structure analysis all support the recognition of a
      sample originating from Toul Krasaing Lake (Cambodia) and one between Kratie and
      Stung Treng (Cambodia) as distinct from the remainder of the sampled range.
      Samples from the main upper Mekong and the Nam Khan River were significantly
      differentiated, but on a time scale inferred to be short (i.e. by genetic drift,
      not sufficient for evolution of new microsatellite alleles). The Mekong stock of
      C. molitorella was strongly differentiated from those from the Red and Pearl
      Rivers, inferred to be on an evolutionary time scale. Finer-scale sampling is
      warranted to further improve the understanding of genetic interactions among fish
      from the Mekong and its tributaries. Detailed studies on the ecology of C.
      molitorella (e.g. migration pathways and preferred spawning habitats) would
      provide useful information to explain the patterns of genetic structure detected
      here, and deepen insights about evolutionary distinctiveness of the population
      units.

PMID- 22380560
TI  - Molecular cloning, characterization and expression analysis of B cell
      translocation gene 1 in grass carp Ctenopharyngodon idella.
AB  - An expressed sequence tag (EST) of B cell translocation gene (BTG) 1 (gcbtg1) was
      obtained from a grass carp Ctenopharyngodon idellus intestinal complementary
      (c)DNA library and the full-length cDNA sequence was acquired by rapid
      amplification of cDNA ends (RACE) technology. The predicted Gcbtg1 protein
      contains the box A and box B motifs which characterized the BTG and transducer of
      ERBB2 (TOB) family. Multiple alignment analysis reveals that Gcbtg1 shares an
      overall identity of 65-94% with Gcbtg1s of other vertebrates. Real-time
      quantitative PCR analysis reveals that the highest expression level of gcbtg1 was
      detected in liver and the lowest in muscle. Western blotting analysis indicates
      that the immunological cross-reactivity occurs between C. idella and human Homo
      sapiens BTG1 protein. A 1008 bp 5'-flanking region sequence was cloned and
      analysed.

PMID- 22380561
TI  - Identification and expression analysis of fabp2 gene from common carp Cyprinus
      carpio.
AB  - Two complementary (c)DNA fragments, including the complete open reading frame of
      fabp2 from the common carp Cyprinus carpio, were cloned by reverse-transcription
      polymerase chain reaction (RT-PCR). Both were putative intestinal-type fabp
      genes, named fabp2a and fabp2b. fabp2b was mainly expressed in the intestine and
      the brain. This gene, however, was nearly not expressed in the liver, heart,
      pancreas and muscle. fabp2a was only expressed at a very low level in the
      intestine. Western blot also showed that Fabp2 is relatively highly expressed in
      the intestine and the brain. Immunohistochemical analysis revealed that Fabp2 is
      widely distributed in the mucosa of the intestine. These findings provide novel
      insights into the fabp2 gene molecular evolution, as well as its potential
      features in the intestine and the brain.

PMID- 22380562
TI  - Notes on the occurrence of the tropical eel Anguilla bicolor bicolor in
      Peninsular Malaysia, Malaysia.
AB  - Previous studies indicated that a tropical freshwater eel Anguilla bicolor
      bicolor occurs in Africa, India, Sri Lanka, Bangladesh, Myanmar, Indonesia and
      Australia, but an intensive survey has indicated an extended distribution range
      for the species into Peninsular Malaysia. Thus, A. b. bicolor is a native
      subspecies of Malaysia.

PMID- 22380563
TI  - Validation of otolith daily increment formation for two temperate syngnathid
      fishes: the pipefishes Stigmatopora argus and Stigmatopora nigra.
AB  - Otoliths were used for the first time to successfully validate the age of members
      of the family Syngnathidae: the spotted pipefish Stigmatopora argus and the wide
      bodied pipefish Stigmatopora nigra. Otolith increments were deposited daily in
      (1) known-age juveniles ranging in age from 0 to 31 days and (2) adults that had
      been stained with alizarin complexone, and a hatch mark was found on all otoliths
      which represented day 0. Otolith increment validation will allow development of
      growth models for S. argus and S. nigra, essential to understanding and managing
      these exclusive seagrass species.

PMID- 22380564
TI  - Effects of altered estuarine submerged macrophyte bed cover on the omnivorous
      Cape stumpnose Rhabdosargus holubi.
AB  - The ecological importance of submerged macrophyte beds to fishes within estuaries
      was investigated through the example of the ubiquitous Cape stumpnose
      Rhabdosargus holubi, an omnivorous, vegetation and estuary-dependent species,
      using stable-isotope techniques and long-term abundance (catch-per-unit-effort)
      data from the East Kleinemonde Estuary, South Africa. Outputs from a Bayesian
      mixing model using delta(13) C and delta(15) N signatures indicated that the
      submerged macrophytes Ruppia cirrhosa and Potamogeton pectinatus were not a
      primary source of nutrition for R. holubi, confirming previous work that revealed
      that macrophytes are consumed but not digested. Long-term seine netting data
      showed reduced abundance of R. holubi during a prolonged period of macrophyte
      senescence, suggesting that submerged macrophyte habitats provide shelter that
      reduces mortality (predation risk) and a food-rich foraging area.

PMID- 22380565
TI  - Are shoals of minnow Phoxinus phoxinus formed by close kin?
AB  - A molecular analysis examining the level of relatedness in shoaling minnows
      Phoxinus phoxinus was conducted. The results revealed that individuals from
      within the same shoal were not more closely related to each other than to
      individuals from other shoals. This led to the conclusion that Schreckstoff may
      be less likely to have evolved in the context of kin selection.

PMID- 22380566
TI  - Rapid and socially induced change of a badge of status.
AB  - This paper reports a new aspect of male signalling in the green swordtail
      Xiphophorus hellerii. Males are highly ornamented and possess a sword (an
      extension of the caudal fin), as well as a lateral stripe that has been shown to
      be a badge of status. Males of one natural population, however, were found to
      quickly change the colour of their lateral stripe to red when socially dominant
      over other males and black when subdominant, thereby exploiting the female
      preference for red stripes while dominant, and avoiding the costs of male
      aggression while subdominant.

PMID- 22380567
TI  - What can phylogeographic breaks in the livebearer Poeciliopsis turrubarensis tell
      about fish community boundaries in western Costa Rica?
AB  - This study asks if the geographic boundary delineating two fish communities in
      western Costa Rica is congruent with a phylogeographic break in a single
      widespread fish species Poeciliopsis turrubarensis (Poeciliidae) that spans this
      area. Such congruence would suggest that a common historical event (e.g.
      geological or climatic) could be responsible for both patterns. It was found that
      there was a shared break across a region in central Costa Rica suggesting a
      common cause may be responsible for both the abrupt shift in fish community
      composition and the genetic break in P. turrubarensis.

PMID- 22380568
TI  - Editorial. The application of systems biology and bioinformatics methods in
      proteomics, transcriptomics and metabolomics.

PMID- 22380569
TI  - Molecular profiling of functional interactions between pre-osteoblastic and
      breast carcinoma cells.
AB  - The relationships between cancer cells and the microenvironment play a critical
      role in cancer growth and development. The bone stroma consists of mesenchymal
      stem cells and mature osteoblasts that promote cancer growth. Yet it is not
      completely understood what are the molecular processes guiding cancer cells
      progression to the bone. In this study, a coculture assay and subsequent gene
      profiling arrays were used to compare the gene expression profile of a pre
      osteoblastic (PO) cell line (MBA-15) with that of a mammary adenocarcinoma (DA3)
      cells. After coculture, cells were separated by magnetic beads based on the
      expression of CD326 antigen. RNA was purified and hybridized on gene expression
      array. The gene expression pattern changes were followed by qRT-PCR. We
      demonstrate that cocultured DA3 cells express elevated levels of genes that
      regulate growth and responses to both hormonal stimulus and wounding, as well as
      reduced expression of genes related to lipid metabolism. Also, cocultured PO
      cells showed reduced expression of cell junction genes. The study presents a
      simplified model system, composed of PO and mammary cancer cells, that
      potentially mimics the molecular interactions in the tumor microenvironment which
      contribute to tumor progression.

PMID- 22380570
TI  - An improved method and data analysis for ultrasound acoustic emissions and xylem
      vulnerability in conifer wood.
AB  - The vulnerability of the xylem to cavitation is an important trait in plant
      drought resistance and has been quantified by several methods. We present a
      modified method for the simultaneous measurement of cavitations, recorded as
      ultrasound acoustic emissions (UAEs), and the water potential, measured with a
      thermocouple psychrometer, in small samples of conifer wood. Analyzing the
      amplitude of the individual signals showed that a first phase, during which the
      mean amplitude increased, was followed by a second phase with distinctly lower
      signal amplitudes. We provide a method to separate the two groups of signals and
      show that for many samples plausible vulnerability curves require rejecting late
      low-energy UAEs. These very likely do not result from cavitations. This method
      was used to analyze the differences between juvenile wood, and early and late
      mature wood in Picea abies (L.) Karst. Juvenile earlywood was more resistant to
      cavitation than mature earlywood or latewood, which we relate to the tracheid
      anatomy of the samples.

PMID- 22380571
TI  - Fulvenallenyl cation (C7H5(+)) and its complex with an argon atom: results of
      high-level quantum-chemical calculations.
AB  - The fulvenallenyl cation (C(7)H(5)(+)) and its complex with an argon atom have
      been studied by explicitly correlated coupled cluster theory at the CCSD(T)
      F12x(x = a, b) level and by the double-hybrid density functional B2PLYP-D. For
      the free cation, an accurate equilibrium structure has been established and
      ground-state rotational constants of A(0) = 8116.4 MHz, B(0) = 2004.3 MHz, and
      C(0) = 1606.9 MHz are predicted. The equilibrium dipole moment is calculated to
      be MU(e) = 1.305 D, with the positive end of the dipole at the acetylenic
      hydrogen site. Anharmonic wavenumbers of C(7)H(5)(+) were obtained by combination
      of harmonic CCSD(T*)-F12a values and B2PLYP-D anharmonic contributions. The most
      intense vibration is the pseudoantisymmetric CC stretching vibration at 2083 cm(
      1). The potential energy surface of the complex C(7)H(5)(+).Ar is characterized
      by two energy minima of C(s) symmetry which are separated by a very low energy
      barrier. The dissociation energy of the most stable structure is predicted to be
      D(0) = 530 +/- 30 cm(-1).

PMID- 22380572
TI  - De novo membranoproliferative glomerulonephritis III in a renal transplant
      patient: case report and review of the literature.
AB  - Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare cause of
      renal failure with a cumulative incidence of 0.3% of all ESRD and 4% of all
      primary glomerulonephritis for types I and II. Membranoproliferative
      glomerulonephritis type III is more uncommon and idiopathic de novo MPGN III in a
      renal transplant patient has not been reported. We present the case of a 57-year
      old white female patient with a diagnosis of lithium toxicity as cause of end
      stage renal disease (ESRD) who developed MPGN III in her allograft 6 years after
      a renal transplant. Despite treatment, she progressed to ESRD within four and a
      half years from the time of diagnosis.

PMID- 22380573
TI  - Role of environmental factors in autoantibody production - importance of a
      detailed analysis in a small cohort.

PMID- 22380574
TI  - An in vitro and in vivo investigation into the suitability of compression coated
      tablets of indomethacin for the treatment of rheumatoid arthritis which follow
      circadian rhythms.
AB  - OBJECTIVE: The aim of this study was to develop chronotherapeutic drug delivery
      system of indomethacin using polyethylene oxide (PEO) with a predetermined lag
      time of 6 h by compression coating technique. MATERIALS AND METHODS: Solid
      dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty
      acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was
      formulated as immediate release core tablet which were further coated with PEO
      (WSR Coagulant or WSR N12 K) using compression coating technique. Compression
      coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet
      weight and coating polymer was considered as optimized formulation, which was
      further characterized by differential scanning calorimetry, X-ray diffractometry,
      Fourier transformed infrared spectroscopy, and scanning electron microscopy.
      RESULTS: The results indicated that there was no chemical incompatibility and
      slight change in surface properties. C(max), area under the curve (AUC(0-t)), and
      T(max) following oral ingestion of commercial capsule (Indocap) and optimized
      formulation (CT 4) were found to be 1973.18 +/- 36.89 ng/mL, 11090.09 +/- 131.21
      ng/mL/h, 0.99 +/- 0.02 h and 2115.46 +/-6 2.61, 10413.14 +/- 299.66 ng/mL/h,
      7.00+/-0.02 h, respectively. CONCLUSION: Unaltered AUC(0-t) and C(max), but
      delayed T(max) indicated clear lag time before immediate release of drug which is
      suitable for treating rheumatoid arthritis following circadian rhythm.

PMID- 22380575
TI  - Diurnal trends in oxidative potential of coarse particulate matter in the Los
      Angeles Basin and their relation to sources and chemical composition.
AB  - To investigate the relationship among sources, chemical composition, and redox
      activity of coarse particulate matter (CPM), three sampling sites were set up up
      in the Los Angeles Basin to collect ambient coarse particles at four time periods
      (morning, midday, afternoon, and overnight) in summer 2009 and winter 2010. The
      generation of reactive oxygen species (ROS) was used to assess the redox activity
      of these particles. Our results present distinct diurnal profiles of CPM-induced
      ROS formation in the two seasons, with much higher levels in summer than winter.
      Higher ROS activity was observed in the midday/afternoon during summertime, while
      the peak activity occurred in the overnight period in winter. Crustal materials,
      the major component of CPM, demonstrated very low water-solubility, in contrast
      with the modestly water-soluble anthropogenic metals, including Ba and Cu. The
      water-soluble fraction of four elements (V, Pd, Cu, and Rh) with primary
      anthropogenic origins displayed the highest associations with ROS activity (R(2)
      > 0.60). Our results show that coarse particles generated by anthropogenic
      activities, despite their low contribution to CPM mass, are important to the
      biological activity of CPM, and that a more targeted control strategy may be
      needed to protect the public health from these toxic CPM sources.

PMID- 22380576
TI  - 9-Methyl-beta-carboline-induced cognitive enhancement is associated with elevated
      hippocampal dopamine levels and dendritic and synaptic proliferation.
AB  - beta-Carbolines (BCs) belong to the heterogenous family of carbolines, which have
      been found exogenously, that is, in various fruits, meats, tobacco smoke, alcohol
      and coffee, but also endogenously, that is, blood, brain and CSF. These exogenous
      and endogenous BCs and some of their metabolites can exert neurotoxic effects,
      however, an unexpected stimulatory effect of 9-methyl-beta-carboline (9-me-BC) on
      dopaminergic neurons in primary mesencephalic cultures was recently discovered.
      The aim of the present study was to extend our knowledge on the stimulatory
      effects of 9-me-BC and to test the hypothesis that 9-me-BC may act as a cognitive
      enhancer. We found that 10 days (but not 5 days) of pharmacological treatment
      with 9-me-BC (i) improves spatial learning in the radial maze, (ii) elevates
      dopamine levels in the hippocampal formation, and (iii) results after 10 days of
      treatment in elongated, more complex dendritic trees and higher spine numbers on
      granule neurons in the dentate gyrus of 9-me-BC-treated rats. Our results
      demonstrate that beyond its neuroprotective/neurorestorative and anti
      inflammatory effects, 9-me-BC acts as a cognitive enhancer in a hippocampus
      dependent task, and that the behavioral effects may be associated with a
      stimulatory impact on hippocampal dopamine levels and dendritic and synaptic
      proliferation.

PMID- 22380577
TI  - Pharmaceutical care issues encountered by post-menopausal osteoporotic women
      prescribed bisphosphonates.
AB  - WHAT IS KNOWN AND OBJECTIVE: Pharmacists have been involved in providing
      comprehensive interventions to osteoporosis patients, but pharmaceutical care
      issues (PCIs) encountered during such interventions have not been well
      documented. Therefore, the aim of this study was to document PCIs encountered by
      post-menopausal osteoporotic women prescribed bisphosphonates. METHODS: A
      randomized controlled study was conducted from September 2005-February 2009 in
      the University Malaya Medical Centre, Malaysia. This main intervention study
      measured the effects of pharmaceutical care on medication adherence, persistence,
      quality of life, knowledge and patient satisfaction. However, this manuscript is
      part of the main intervention study and focuses only on the PCIs encountered.
      INCLUSION CRITERIA: post-menopausal women diagnosed with osteoporosis (T-score<=
      2.5/low-trauma fracture) and prescribed weekly alendronate/risedronate. EXCLUSION
      CRITERIA: those with metabolic bone disease and could not communicate in English.
      The PCIs identified were collected via personal interviews or telephone calls,
      and each participant was followed-up for a period of 2 years. All PCIs were
      discussed with and confirmed by a physician. RESULTS AND DISCUSSION: Of the 198
      participants recruited, 64 (32.3%) experienced adverse effects because of
      bisphosphonates whereas one participant (0.5%) refused to start bisphosphonates
      because of fear of adverse effects. Most adverse effects [50 (74.6%)] were
      reported during the first 3 months of therapy with gastrointestinal problems
      being the main issue [23 (11.6%)]. Of the nine participants (4.5%) who
      discontinued bisphosphonates, only three agreed to take another medication. From
      the 97 PCIs identified, 77 issues could be classified as drug-related problems
      [according to the Pharmaceutical Care Network Europe Classification v6.2]. There
      were 87 causes, 178 interventions and 77 outcomes. The main problem and cause of
      the PCIs encountered were adverse drug events (83.1% and 74.7% respectively),
      whereas the main intervention provided was patient counselling (41.0%). All
      problems were solved (98.5%) except for one because of the lack of cooperation of
      a patient. After 2 years, 36 participants (20%) were no longer persistent with
      therapy, 19 (10.6%) did not have clinic follow-up and 53 (26.8%) did not have a
      bone mineral density scan. WHAT IS NEW AND CONCLUSION: The main PCIs identified
      were related to the use of bisphosphonates and its adverse effects. The study
      showed that the presence of a clinical pharmacist has enabled patients to voice
      their medication-related issues and to allow appropriate recommendations and
      actions to be taken to resolve these issues.

PMID- 22380578
TI  - Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire.

PMID- 22380579
TI  - Th17 and regulatory T cells in women with recurrent pregnancy loss.
AB  - The immune system of pregnant women is tightly controlled to defend against
      microbial infections and at the same time, to accept an embryo or the fetus,
      which are expressing semi-allogenic paternal antigens. Furthermore, inflammation
      like processes are crucial for tissue growth, remodeling, and differentiation of
      the decidua during pregnancy. Dysregulation of elaborate immune control may lead
      reproductive failure, such as implantation failure, recurrent pregnancy loss
      (RPL), preterm birth, intrauterine fetal growth restriction, and preeclampsia.
      Until recent years, a balance between Th1 and Th2 cells was believed to be the
      key immune regulatory mechanism of T-cell immunology especially during pregnancy.
      Since the identification of regulatory T cells was made, the mechanism of immune
      regulation has become a major issue in immunologic research. Also, the recent
      identification of Th17 cells has drawn our attention to a new immune effector.
      The balance between Th17 and regulatory T cells may explain more about the
      pathophysiology of reproductive failure. This review will discuss relevant human
      literature on regulatory T and Th17 cells in normal reproductive physiology and
      in women with RPL and infertility.

PMID- 22380580
TI  - Prechemotherapy differences in response inhibition in breast cancer patients
      compared to controls: a functional magnetic resonance imaging study.
AB  - Prechemotherapy neuroimaging data are lacking in posttreatment cognitive
      impairment studies. Breast cancer patients and noncancer controls were scanned
      prior to chemotherapy during a response inhibition task. Task reaction times and
      error rates, as well as neuropsychological tests, hospital records, and salivary
      biomarkers, were investigated, yielding no significant group differences.
      Significant group differences observed for the functional magnetic resonance
      imaging (fMRI) data depended on the type of analysis performed, most consistently
      implicating widespread attenuated activations in patients. The patient group also
      revealed considerable variability in task-related brain activity. These
      pretreatment differences highlight the need to understand the effects of
      confounding variables before considering posttreatment effects.    Role of the
      funding source: The Canadian Breast Cancer Foundation has funded this project.
      Their contribution was solely financial support.

PMID- 22380581
TI  - Transient gut retention and persistence of Salmonella through metamorphosis in
      the lesser mealworm, Alphitobius diaperinus (Coleoptera: Tenebrionidae).
AB  - AIMS: This study was undertaken to determine the retention of Salmonella through
      Alphitobius diaperinus metamorphosis and its contribution, through defecation, to
      external contamination. METHODS AND RESULTS: Insects were exposed to a tagged
      Salmonella enterica and evaluated for external elimination. (i) Each day for 3
      weeks, a filter collected frass from a restrained insect for analysis. (ii)
      Exposed larvae in a closed container were followed through pupation, and newly
      emerged adults were examined for their retention of marker bacteria. CONCLUSIONS:
      Exposed adults and larvae produced Salmonella-positive frass for an average of 8
      days, ranging from 6 to 11 days and 6 to 12 days, respectively. Nineteen per cent
      of the larvae carried Salmonella through metamorphosis and eclosion, with 5% of
      the pupal exuviae being positive as well. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Many sources of foodborne pathogens within the poultry production facilities,
      including reservoir populations, currently go unrecognized. This diminishes the
      ability of producers to mitigate the transfer of pathogens between animals,
      humans and the environment. Poultry management standards accept the reutilization
      of litter. Alphitobius diaperinus survive between flock rotations on the
      reutilized litter, and it was demonstrated in this study that the Salmonella they
      carry can survive with them.

PMID- 22380582
TI  - Famciclovir-induced leukocytoclastic vasculitis.

PMID- 22380583
TI  - The road ahead: theoretical models to guide new sex research.

PMID- 22380584
TI  - Different perspectives on the sex-attachment link: towards an emotion
      motivational account.
AB  - Although the link between sex and attachment was made decades ago (Hazan &
      Shaver, 1987), theories on sexual and attachment functioning have been developed
      in relative isolation. Recent efforts to integrate both literatures have been
      complicated by the fact that the sex-attachment link has been approached from
      very different perspectives, including biological, evolutionary, developmental,
      cognitive, and social psychology approaches. Also, at the empirical level,
      research on sex and attachment lacks overarching synthesis. This article gives an
      overview of the most important theoretical ideas and empirical insights on sex
      and attachment. It starts with describing general models that approach the sex
      attachment link from an evolutionary and neurobiological perspective. Then, it
      summarizes theoretical and empirical ideas of attachment theory and describes how
      attachment style differences are manifested in intimate and sexual relationships.
      Research so far has been limited to studying the predicted link between sex and
      attachment in terms of broad descriptives, and it would benefit the literature to
      specify the processes and pathways that mediate the sex-attachment link. After a
      short discussion of the functional similarities between the sexual and the
      attachment systems, the article describes some specific--dynamical--models that
      focus on the emotional and cognitive-motivational processes through which
      attachment schemas influence sexual experiences. Such an emotion-motivational
      perspective on sex and attachment can help to organize theoretical ideas and
      empirical findings and eventually promote an integrative view on how attachment
      dynamics can interact with sexual experiences.

PMID- 22380585
TI  - Sexual expression in later life: a review and synthesis.
AB  - In the past decade, researchers have begun to study the sexual functioning of
      typical older persons. This review summarizes literature on the sexuality of men
      and women over age 50 as researched by social and health scientists. Research on
      the relationship of biological factors (changes accompanying aging), health
      (physical, mental, and medication use), psychological factors (attitudes,
      information about sex), relationship factors (status, satisfaction), and sexual
      functioning (desire, dysfunctions, treatment) to sexual behavior is reviewed. The
      review suggests that (a) men and women remain sexually active into their 70s and
      80s, (b) aging-related physical changes do not necessarily lead to decline in
      sexual functioning, and (c) good physical and mental health, positive attitudes
      toward sex in later life, and access to a healthy partner are associated with
      continued sexual activity. In turn, regular sexual expression is associated with
      good physical and mental health. Progress in understanding later life sexuality
      requires development of comprehensive theoretical models, a broad focus on
      intimacy, attention to measures and samples, and research on couples. Progress in
      understanding is especially important, given the aging of populations.

PMID- 22380586
TI  - Victimization experiences of lesbian, gay, and bisexual individuals: a meta
      analysis.
AB  - This meta-analysis quantitatively compiled the results of studies from 1992 to
      2009 to determine the prevalence and types of victimization experienced by
      lesbian, gay, and bisexual (LGB) individuals. Based on the results of three
      searches, 386 studies were retrieved and coded. Comparisons were made across all
      LGB individuals (138 studies), between LGB and heterosexual individuals (65
      studies), and between LGB females and males (53 studies), with over 500,000
      participants. Multiple types of victimization were coded, including
      discrimination, physical assault, and school victimization. Findings revealed
      that for LGB individuals, reports of victimization experiences were substantial
      (e.g., 55% experienced verbal harassment, and 41% experienced discrimination) and
      some types have increased since a 1992 review, while others have decreased. LGB
      individuals experienced greater rates of victimization than heterosexual
      individuals (range: d = .04-.58). LGB males experienced some types of
      victimization more than LGB females (e.g., weapon assault and being robbed) but,
      overall, the gender differences were small. It can be concluded that LGB
      individuals still experience a substantial amount of victimization. Implications
      for research methods are discussed, including recommendations for sampling and
      measurement of victimization.   [Supplementary materials are available for this
      article. Go to the publisher's online edition of Journal of Sex Research for the
      following free supplemental resource(s): Supplementary Tables. These tables are
      referred to in the text of this article as "Table S1," "Table S2," etc.].

PMID- 22380587
TI  - Eroticizing inequality in the United States: the consequences and determinants of
      traditional gender role adherence in intimate relationships.
AB  - This article reviews the research on traditional gender-role adherence and
      sexuality for heterosexual men and women. Specifically, the consequences and
      predictors of following traditional gender roles of female submissiveness and
      male dominance in sexual relationships is examined. Despite evidence that men and
      women's sexual roles are becoming more egalitarian over time, empirical evidence
      suggests that the traditional sexual roles continue to dominate heterosexual
      relations. This article explores whether the sexual context is one in which both
      men and women feel particularly compelled to engage in gender stereotypic
      behavior, and why. In addition, this article reports on research that finds that
      men and women have automatic associations between sexuality and power that
      reinforce their gender stereotypic behavior in sexual contexts. The negative
      effects of traditional gender-role adherence for women's sexual problems and
      satisfaction is demonstrated. This article concludes that traditional sexual
      scripts are harmful for both women's and men's ability to engage in authentic,
      rewarding sexual expression, although the female submissive role may be
      particularly debilitating. Future directions of research are suggested, including
      interventions to reduce women's adherence to the sexually submissive female
      script.

PMID- 22380588
TI  - Body image and female sexual functioning and behavior: a review.
AB  - Knowledge in the research fields of body image and sexuality has significantly
      increased in the last decade. In this review, data from 57 studies were compiled
      for a review of empirical evidence regarding the association between sexuality
      and body image among healthy women. The overall conclusion is that body image
      issues can affect all domains of sexual functioning. Cognitions and self
      consciousness seem to be key factors in understanding the complex relationships
      between women's body image and sexuality. Body evaluations and cognitions not
      only interfere with sexual responses and experiences during sexual activity, but
      also with sexual behavior, sexual avoidance, and risky sexual behavior.

PMID- 22380589
TI  - Investigating the impact of inquiry mode on self-reported sexual behavior:
      theoretical considerations and review of the literature.
AB  - Measurement of sexual behaviors is typically reliant on retrospective self
      reports of behaviors. Historically, self-reported sexual behavior data were
      primarily collected through face-to-face interviews or paper-and-pencil
      questionnaires, as these were the only modes of inquiry available. In recent
      decades, technological innovations such as telephones, computers, and the
      Internet have expanded the self-report inquiry modes available. The addition of
      these new inquiry modes further complicates the ability of sex researchers to
      evaluate the quality of research results and compare findings across studies.
      Self-report sexual behavior data are vulnerable to participation biases, as well
      as to sources of bias in individual responses, such as recollection and social
      desirability bias. This is true regardless of the inquiry mode being used, but
      some modes may be more vulnerable to bias than others. This review examines the
      available research regarding self-report sexual behavior research, inquiry mode,
      and relative bias across modes. The review also provides recommendations for
      advancing the current understanding of inquiry mode effects within sexual
      behavior research. Specifically, by shifting the focus away from evaluating
      specific modes of inquiry toward examination of factors common across all modes,
      researchers will be better able to interpret existing research and improve the
      designs of future studies as well.

PMID- 22380590
TI  - Sexual selection on human faces and voices.
AB  - Humans are highly sexually dimorphic primates, and some of the most conspicuous
      human sex differences occur in the face and voice. Consequently, this article
      utilizes research findings on human faces and voices to illustrate how human sex
      differences may have arisen by sexual selection (i.e., the type of natural
      selection favoring traits that increase mating opportunities). Evidence
      suggesting that sexual selection shaped women's faces and voices is reviewed.
      However, sexual selection likely operated more strongly on men over human
      evolution. Thus, this research focuses on two types of sexual selection operating
      on men: female mate choice, which favors traits that attract females, and male
      contests, which favor traits for excluding competitors from mates by force or
      threat of force. This article demonstrates how masculine faces and voices
      advertize critical information about men's mate value and threat potential, and
      reviews evidence that women's preferences and men's deference to masculine faces
      and voices reflect this information content. Data suggesting that facial and
      vocal masculinity influences men's mating opportunities and reproduction are
      discussed, and the article concludes by highlighting directions for future
      research.

PMID- 22380591
TI  - Follow-up of women with gestational diabetes in the Tehran Lipid and Glucose
      Study (TLGS): a population-based cohort study.
AB  - AIM: Women with gestational diabetes (GDM) are at increased risk of developing
      type 2 diabetes mellitus (T2DM), but there is disagreement regarding this
      conversion rate or its cardiovascular consequences. We investigated the metabolic
      and cardiovascular consequences of women with GDM in a population-based cohort
      study. MATERIAL AND METHODS: Three groups of women were selected from the Tehran
      Lipid and Glucose Study (TLGS) and followed up for an average 9 years: women with
      prior history of GDM (n = 29); women with history of macrosomia or stillbirth
      without GDM (MC-ST) (n = 570), and age- and BMI-matched controls (n = 628). The
      incidence of T2DM, hypertension (HTN) and dyslipidemia were compared between
      these groups. Statistical significance was set at P < 0.05. RESULTS: During the 9
      year follow-up, T2DM was diagnosed in 27.3% of women with GDM in comparison to
      9.5% among the control group (P < 0/001); 7.4% of the MC-ST group versus 8.9% of
      control group developed T2DM during the study follow-up (P = 0/03). There was no
      significant difference in the incidence of HTN or dyslipidemia between these
      groups (P > 0/05). CONCLUSION: Women with a history of GDM are at higher risk for
      developing T2DM later in life. The timely recognition of GDM may provide a
      'teachable moment' during which women could be motivated to implement lifestyle
      modifications to reduce their T2DM risk.

PMID- 22380592
TI  - Genetic polymorphism and natural selection of Duffy binding protein of Plasmodium
      vivax Myanmar isolates.
AB  - BACKGROUND: Plasmodium vivax Duffy binding protein (PvDBP) plays an essential
      role in erythrocyte invasion and a potential asexual blood stage vaccine
      candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly
      amino terminal cysteine-rich region (PvDBPII), represents a major impediment to
      the successful design of a protective vaccine against vivax malaria. In this
      study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P.
      vivax isolates were analysed. METHODS: Fifty-four P. vivax infected blood samples
      collected from patients in Myanmar were used. The region flanking PvDBPII was
      amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic
      characters and natural selection of the region were analysed using the DnaSP and
      MEGA4 programs. RESULTS: Thirty-two point mutations (28 non-synonymous and four
      synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax
      isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were
      identified in Myanmar P. vivax isolates and that the region has evolved under
      positive natural selection. High selective pressure preferentially acted on
      regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also
      be played a role in the resulting genetic diversity of PvDBPII. CONCLUSIONS:
      PvDBPII of Myanmar P. vivax isolates displays a high level of genetic
      polymorphism and is under selective pressure. Myanmar P. vivax isolates share
      distinct types of PvDBPII alleles that are different from those of other
      geographical areas. These results will be useful for understanding the nature of
      the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.

PMID- 22380593
TI  - Amphiphilic polyanhydride nanoparticles stabilize Bacillus anthracis protective
      antigen.
AB  - Advancements toward an improved vaccine against Bacillus anthracis, the causative
      agent of anthrax, have focused on formulations composed of the protective antigen
      (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA,
      antigen stability is a primary concern for vaccine development. Thus, there is a
      need for a delivery system capable of preserving the immunogenicity of PA through
      all the steps of vaccine fabrication, storage, and administration. In this work,
      we demonstrate that biodegradable amphiphilic polyanhydride nanoparticles, which
      have previously been shown to provide controlled antigen delivery, antigen
      stability, immune modulation, and protection in a single dose against a
      pathogenic challenge, can stabilize and release functional PA. These
      nanoparticles demonstrated polymer hydrophobicity-dependent preservation of the
      biological function of PA upon encapsulation, storage (over extended times and
      elevated temperatures), and release. Specifically, fabrication of amphiphilic
      polyanhydride nanoparticles composed of 1,6-bis(p-carboxyphenoxy)hexane and 1,8
      bis(p-carboxyphenoxy)-3,6-dioxaoctane best preserved PA functionality. These
      studies demonstrate the versatility and superiority of amphiphilic nanoparticles
      as vaccine delivery vehicles suitable for long-term storage.

PMID- 22380594
TI  - DNA methylation and genome rearrangement characteristics of phase change in
      cultured shoots of Sequoia sempervirens.
AB  - Epigenetic machinery regulates the expression of individual genes and plays a
      crucial role in globally shaping and maintaining developmental patterning. We
      studied the extent of DNA methylation in the nucleus, mitochondrion and
      chloroplast in cultured Sequoia sempervirens (coast redwood) adult, juvenile and
      rejuvenated shoots by measuring the ratio of methylcytosine to total cytosine
      using high-performance liquid chromatography (HPLC). We also analyzed nuclear DNA
      (nuDNA) polymorphisms of different shoot types by methylation-sensitive amplified
      fragment length polymorphism (MSAP) and Southern blot analysis. The extent of
      nuDNA methylation was greater in the adult vegetative than juvenile and
      rejuvenated shoots (8% vs 6.5-7.5%). In contrast, the proportion of
      methylcytosine was higher in mitochondrial DNA (mDNA) of juvenile and rejuvenated
      shoots than adult shoots (6.6% vs 7.8-8.2%). MSAP and Southern blot analyses
      identified three MSAP fragments which could be applied as phase-specific
      molecular markers. We also found nuclear genome and mtDNA rearrangement may be as
      important as DNA methylation status during the phase change. Our findings
      strongly suggest that DNA methylation and genome rearrangement may affect the
      dynamic tissue- and cell type-specific changes that determine the developmental
      phase of S. sempervirens shoots.

PMID- 22380595
TI  - Gastrointestinal nematodes in rotationally grazing ewes in the mountainous region
      of central Mexico.
AB  - The aims of this study were to determine the frequency of egg shedding
      (percentage of egg-positive faecal samples) and faecal egg counts (FEC) over 13
      months in two different breeds of ewes, both pregnant and non-pregnant, in a
      mountainous region of central Mexico. Additionally, the effect of ivermectin and
      albendazole treatments on FEC reduction was recorded. The study also aimed to
      relate temperature and rainfall to FEC. The gastrointestinal nematode (GIN) third
      stage larvae genera recovered from both faeces and grassland pastures in a
      temperate region were also assessed. Faecal samples were collected from ewes at
      monthly intervals for 13 months to investigate the FEC population of GIN larvae,
      their concentration and genera in grass samples collected from grazed and rested
      pastures. Egg-shedding frequency ranged from 0 to 92% and FEC from 0 to 12,000
      eggs per g faeces (epg), with counts in Suffolk higher than in Dorset ewes. The
      identified genera were Haemonchus, Trichostrongylus, Teladorsagia, Cooperia,
      Oesophagostomum, Bunostomum, Nematodirus and Strongyloides. Haemonchus and
      Trichostrongylus were the most common genera. The number of L3 was higher in
      grazing lands than in those at rest. The highest FEC were recorded in the dry
      season due to peripartum, but the highest L3 counts were recorded in the rainy
      season. The coexistence of species of different geographical distributions at
      this site may be because there is a confluence of Nearctic and Neotropical
      geographic regions; thus, despite the temperate climate, tropical species can be
      found. Additionally, this study suggests that increasing temperatures could
      favour the presence of different tropical GIN species together with typical
      temperate-zone GIN species.

PMID- 22380596
TI  - Assessment of a rule-based virtual screening technology (INDDEx) on a benchmark
      data set.
AB  - The Investigational Novel Drug Discovery by Example (INDDEx) package has been
      developed to find active compounds by linking activity to chemical substructure
      and to guide the process of further drug development. INDDEx is a machine
      learning technique, based on forming qualitative logical rules about
      substructural features of active molecules, weighting the rules to form a
      quantitative model, and then using the model to screen a molecular database.
      INDDEx is shown to be able to learn from multiple active compounds and to be
      useful for scaffold-hopping when performing virtual screening, giving high
      retrieval rates even when learning from a small number of compounds. Across the
      data sets tested, at 1% of the data, INDDEx was found to have average enrichment
      factors of 69.2, 82.7, and 90.4 when learning from 2, 4, and 8 active ligands,
      respectively. At 0.1% of the data, INDDEx had average enrichment factors of 492,
      631, and 707 when learning from 2, 4, and 8 active ligands, respectively.
      Excluding all ligands with more than 0.5 Tanimoto Maximum Common Substructure,
      INDDEx had average enrichment factors at 1% of 52.3, 63.6, and 66.9 when learning
      from 2, 4, and 8 active ligands, respectively. The performance of INDDEx is
      compared with that of eHiTS LASSO, PharmaGist, and DOCK.

PMID- 22380597
TI  - YdiV: a dual function protein that targets FlhDC for ClpXP-dependent degradation
      by promoting release of DNA-bound FlhDC complex.
AB  - YdiV is an EAL-like protein that acts as a post-transcriptional, negative
      regulator of the flagellar master transcriptional activator complex, FlhD(4)C(2),
      in Salmonella enterica to couple flagellar gene expression to nutrient
      availability. Mutants defective in ClpXP protease no longer exhibit YdiV
      dependent inhibition of FlhD(4)C(2)-dependent transcription under moderate YdiV
      expression conditions. ClpXP protease degrades FlhD(4)C(2), and this degradation
      is accelerated in the presence of YdiV. YdiV complexed with both free and DNA
      bound FlhD(4)C(2); and stripped FlhD(4)C(2) from DNA. A L22H substitution in FlhD
      was isolated as insensitive to YdiV inhibition. The FlhD L22H substitution
      prevented the interaction of YdiV with free FlhD(4)C(2) and the ability of YdiV
      to release FlhD(4)C(2) bound to DNA. These results demonstrate that YdiV prevents
      FlhD(4)C(2)-dependent flagellar gene transcription and acts as a putative adaptor
      to target FlhD(4)C(2) for ClpXP-dependent proteolysis. Our results suggest that
      YdiV is an EAL-like protein that has evolved from a dicyclic-GMP
      phosphodiesterase into a dual-function regulatory protein that connects flagellar
      gene expression to nutrient starvation.

PMID- 22380598
TI  - Short communication: risk of elevated total cholesterol/high-density lipoprotein
      cholesterol ratio after antiretroviral therapy in HIV/hepatitis C virus patients.
AB  - Dyslipidemia from highly active antiretroviral therapy (HAART) use has been
      reported to be less severe among persons with HIV and hepatitis C (HCV) compared
      to those with HIV monoinfection. However, the effect on lipoprotein ratios is
      less clear. The total cholesterol/high-density lipoprotein ratio (TC/HDL-C ratio)
      is a robust measure of cardiovascular disease (CVD) risk but has not been
      examined in the context of HIV/HCV-coinfected patients. We compared the TC/HDL-C
      ratio before HAART initiation and after at least 6 months on HAART between
      patients monoinfected with HIV and coinfected with HIV and HCV. Pre- and post
      HAART TC, HDL-C, and non-HDL-C were also assessed. Although TC, HDL-C, and non
      HDL-C significantly increased after HAART initiation in both HIV and HIV/HCV
      patients, the TC/HDL-C ratio did not. In addition, although the pre- and post
      HAART TC, HDL-C, non-HDL-C, and TC/HDL-C ratio were significantly different
      between HIV and HIV/HCV patients, the magnitude in the change from pre- to post
      HAART was not significantly different between infection groups. These results
      persisted after controlling for age, sex, race, current pharmacotherapy for
      lipoproteins, body mass index, and current CD4 cell count. The magnitude of
      change in the TC/HDL-C ratio after HAART initiation is not significantly
      different between HIV and HIV/HCV patients, suggesting subsequent CVD risk in
      HIV/HCV patients may be greater than currently appreciated.

PMID- 22380599
TI  - The Bcl-2 proteins Noxa and Bcl-xL co-ordinately regulate oxidative stress
      induced apoptosis.
AB  - Because the detailed molecular mechanisms by which oxidative stress induces
      apoptosis are not completely known, we investigated how the complex Bcl-2 protein
      network might regulate oxidative stress-induced apoptosis. Using MEFs (mouse
      embryonic fibroblasts), we found that the endogenous anti-apoptotic Bcl-2 protein
      Bcl-xL prevented apoptosis initiated by H(2)O(2). The BH3 (Bcl-2 homology 3)-only
      Bcl-2 protein Noxa was required for H(2)O(2)-induced cell death and was the
      single BH3-only Bcl-2 protein whose pro-apoptotic activity was completely
      antagonized by endogenous Bcl-xL. Upon H(2)O(2) treatment, Noxa mRNA displayed
      the greatest increase among BH3-only Bcl-2 proteins. Expression levels of the
      anti-apoptotic Bcl-2 protein Mcl-1 (myeloid cell leukaemia sequence 1), the
      primary binding target of Noxa, were reduced in H(2)O(2)-treated cells in a Noxa
      dependent manner, and Mcl-1 overexpression was able to prevent H(2)O(2)-induced
      cell death in Bcl-xL-deficient MEF cells. Importantly, reduction of the
      expression of both Mcl-1 and Bcl-xL caused spontaneous cell death. These studies
      reveal a signalling pathway in which H(2)O(2) activates Noxa, leading to a
      decrease in Mcl-1 and subsequent cell death in the absence of Bcl-xL expression.
      The results of the present study indicate that both anti- and pro-apoptotic Bcl-2
      proteins co-operate to regulate oxidative stress-induced apoptosis.

PMID- 22380600
TI  - Dynamic training of the lumbar musculature to prevent recurrence of acute low
      back pain: a randomized controlled trial using a daily pain recall for 1 year.
AB  - PURPOSE: The purpose of this experiment was to quantify lumbar muscle endurance
      training for individuals with a recent episode of acute low back pain (LBP) (>=
      moderate pain for >= 2 days) and to observe whether the training would reduce the
      rate and severity of recurrent LBP episodes. METHOD: Twenty-six participants who
      were pain-free at the time of the study were randomly divided into a high
      intensity back endurance (HIBE)-trained or a low intensity abdominal (LOAB)
      trained (control) group. The HIBE-trained group performed preloaded maximum
      isokinetic exertions of the back extensors (five sets of 10 repetitions, 3 days a
      week for 4 weeks, totaling 12 sessions). The LOAB-trained group performed low
      intensity isometric contractions on their abdominals that had minimal effect on
      their back musculature. The two groups reported daily pain logs on a weekly basis
      on an interactive voice response telephone system for 1 year. RESULTS: The HIBE
      trained group experienced more pain days (p = 0.038) in the minor and moderate
      categories and more episodes of acute LBP than the LOAB-trained group. However,
      there was a trend of less pain in the severe, intense and excruciating categories
      in the HIBE-trained group. CONCLUSIONS: The results of this experiment did not
      provide evidence that short-term intense training of the low back musculature
      provides protection against future episodes of LBP.

PMID- 22380601
TI  - On the equivalence of conformational and enantiomeric changes of atomic
      configuration for vibrational circular dichroism signs.
AB  - We study systematically the vibrational circular dichroism (VCD) spectra of the
      conformers of a simple chiral molecule, with one chiral carbon and an "achiral"
      alkyl substituent of varying length. The vibrational modes can be divided into a
      group involving the chiral center and its direct neighbors and the modes of the
      achiral substituent. Conformational changes that consist of rotations around the
      bond from the next-nearest neighbor to the following carbon, and bond rotations
      further in the chain, do not affect the modes around the chiral center. However,
      conformational changes within the chiral fragment have dramatic effects, often
      reversing the sign of the rotational strength. The equivalence of the effect of
      enantiomeric change of the atomic configuration and conformational change on the
      VCD sign (rotational strength) is studied. It is explained as an effect of atomic
      characteristics, such as the nuclear amplitudes in some vibrational modes as well
      as the atomic polar and axial tensors, being to a high degree determined by the
      local topology of the atomic configuration. They reflect the local physics of the
      electron motions that generate the chemical bonds rather than the overall shape
      of the molecule.

PMID- 22380602
TI  - Identification of the para-nitrophenol catabolic pathway, and characterization of
      three enzymes involved in the hydroquinone pathway, in Peudomonas sp. 1-7.
AB  - BACKGROUND: para-Nitrophenol (PNP), a priority environmental pollutant, is
      hazardous to humans and animals. However, the information relating to the PNP
      degradation pathways and their enzymes remain limited. RESULTS: Pseudomonas sp.1
      7 was isolated from methyl parathion (MP)-polluted activated sludge and was shown
      to degrade PNP. Two different intermediates, hydroquinone (HQ) and 4
      nitrocatechol (4-NC) were detected in the catabolism of PNP. This indicated that
      Pseudomonas sp.1-7 degraded PNP by two different pathways, namely the HQ pathway,
      and the hydroxyquinol (BT) pathway (also referred to as the 4-NC pathway). A gene
      cluster (pdcEDGFCBA) was identified in a 10.6 kb DNA fragment of a fosmid
      library, which cluster encoded the following enzymes involved in PNP degradation:
      PNP 4-monooxygenase (PdcA), p-benzoquinone (BQ) reductase (PdcB), hydroxyquinol
      (BT) 1,2-dioxygenase (PdcC), maleylacetate (MA) reductase (PdcF), 4
      hydroxymuconic semialdehyde (4-HS) dehydrogenase (PdcG), and hydroquinone (HQ)
      1,2-dioxygenase (PdcDE). Four genes (pdcDEFG) were expressed in E. coli and the
      purified pdcDE, pdcG and pdcF gene products were shown to convert HQ to 4-HS, 4
      HS to MA and MA to beta-ketoadipate respectively by in vitro activity assays.
      CONCLUSIONS: The cloning, sequencing, and characterization of these genes along
      with the functional PNP degradation studies identified 4-NC, HQ, 4-HS, and MA as
      intermediates in the degradation pathway of PNP by Pseudomonas sp.1-7. This is
      the first conclusive report for both 4-NC and HQ- mediated degradation of PNP by
      one microorganism.

PMID- 22380603
TI  - Novel cGMP efflux inhibitors identified by virtual ligand screening (VLS) and
      confirmed by experimental studies.
AB  - Elevated intracellular levels of cyclic guanosine monophosphate (cGMP) may induce
      apoptosis, and at least some cancer cells seem to escape this effect by increased
      efflux of cGMP, as clinical studies have shown that extracellular cGMP levels are
      elevated in various types of cancer. The human ATP binding cassette (ABC)
      transporter ABCC5 transports cGMP out of cells, and inhibition of ABCC5 may have
      cytotoxic effects. Sildenafil inhibits cGMP efflux by binding to ABCC5, and in
      order to search for potential novel ABCC5 inhibitors, we have identified
      sildenafil derivates using structural and computational guidance and tested them
      for the cGMP efflux effect. Eleven compounds from virtual ligand screening (VLS)
      were tested in vitro, using inside-out vesicles (IOV), for inhibition of cGMP
      efflux. Seven of 11 compounds predicted by VLS to bind to ABCC5 were more potent
      than sildenafil, and the two most potent showed K(i) of 50-100 nM.

PMID- 22380604
TI  - Correlation-matrix analysis of two-color coincidence events in single-molecule
      fluorescence experiments.
AB  - We introduce a robust and relatively easy-to-use method to evaluate the quality
      of two-color (or more) fluorescence coincidence measurements based on close
      investigation of the coincidence correlation-matrix. This matrix contains
      temporal correlations between the number of detected bursts in individual
      channels and their coincidences. We show that the Euclidian norm of a vector
      Gamma derived from elements of the correlation matrix takes a value between 0 and
      2 depending on the relative coincidence frequency. We characterized the Gamma
      norm and its dependence on various experimental conditions by computer
      simulations and fluorescence microscopy experiments. Single-molecule experiments
      with two differently colored dye molecules diffusing freely in aqueous solution,
      a sample that generates purely random coincidence events, return a Gamma-norm
      less than one, depending on the concentration of the fluorescent dyes. As perfect
      coincidence sample we monitored broad autofluorescence of 2.8 MUm beads and
      determined the Gamma-norm to be maximal and close to two. As in realistic
      diagnostic applications, we show that two-color coincidence detection of single
      stranded DNA molecules, using differently labeled Molecular Beacons hybridizing
      to the same target, reveal a value between one and two representing a mixture of
      an optimal coincidence sample and a sample generating random coincidences. The
      Gamma-norm introduced for data analysis provides a quantifiable measure for
      quickly judging the outcome of single-molecule coincidence experiments and
      estimating the quality of detected coincidences.

PMID- 22380605
TI  - Subunit composition of alpha5-containing nicotinic receptors in the rodent
      habenula.
AB  - Gene association studies in humans have linked the alpha5 subunit gene CHRNA5 to
      an increased risk for nicotine dependence. In the CNS, nicotinic acetylcholine
      receptors (nAChRs) that contain the alpha5 subunit are expressed at relatively
      high levels in the habenulo-interpeduncular system. Recent experimental evidence
      furthermore suggests that alpha5-containing receptors in the habenula play a key
      role in controlling the intake of nicotine in rodents. We have now analysed the
      subunit composition of hetero-oligomeric nAChRs in the habenula of postnatal day
      18 (P18) C57Bl/6J control mice and of mice with deletions of the alpha5, the
      beta2, or the beta4 subunit genes. Receptors consisting of alpha3beta4* clearly
      outnumbered alpha4beta2*-containing receptors not only in P18 but also in adult
      mice. We found low levels of alpha5-containing receptors in both mice (6%) and
      rats (2.5% of overall nAChRs). Observations in beta2 and beta4 null mice indicate
      that although alpha5 requires the presence of the beta4 subunit for assembling
      (but not of beta2), alpha5 in wild-type mice assembles into receptors that also
      contain the subunits alpha3, beta2, and beta4.

PMID- 22380606
TI  - Thermodynamic stability, spectroscopic identification, and gas storage capacity
      of CO2-CH4-N2 mixture gas hydrates: implications for landfill gas hydrates.
AB  - Landfill gas (LFG), which is primarily composed of CH(4), CO(2), and N(2), is
      produced from the anaerobic digestion of organic materials. To investigate the
      feasibility of the storage and transportation of LFG via the formation of
      hydrate, we observed the phase equilibrium behavior of CO(2)-CH(4)-N(2) mixture
      hydrates. When the specific molar ratio of CO(2)/CH(4) was 40/55, the equilibrium
      dissociation pressures were gradually shifted to higher pressures and lower
      temperatures as the mole fraction of N(2) increased. X-ray diffraction revealed
      that the CO(2)-CH(4)-N(2) mixture hydrate prepared from the CO(2)/CH(4)/N(2)
      (40/55/5) gas mixture formed a structure I clathrate hydrate. A combination of
      Raman and solid-state (13)C NMR measurements provided detailed information
      regarding the cage occupancy of gas molecules trapped in the hydrate frameworks.
      The gas storage capacity of LFG hydrates was estimated from the experimental
      results for the hydrate formations under two-phase equilibrium conditions. We
      also confirmed that trace amounts of nonmethane organic compounds do not affect
      the cage occupancy of gas molecules or the thermodynamic stability of LFG
      hydrates.

PMID- 22380607
TI  - Psychometric properties of the Norwegian Person-centred Climate Questionnaire
      from a nursing home context.
AB  - BACKGROUND: The physical and psychosocial environments in nursing homes influence
      the residents' everyday life as well as their well-being and thriving. The
      staff's perceptions of and relationships with the residents are crucially
      important to quality care. Quality care is described often as person-centred. Few
      measurement tools exist that focus on person-centred care in nursing homes.
      OBJECTIVE: The aim of this study was to evaluate the psychometric properties of
      the Norwegian version of the Person-centred Climate Questionnaire-Staff version
      (PCQ-S). DESIGN: This study had a cross-sectional survey design. PARTICIPANTS AND
      SETTINGS: Two hundred and nine healthcare and support staff in five nursing homes
      in the eastern part of Norway. METHODS: The Swedish PCQ-S was translated into
      Norwegian with forward and backward translation. The relevance of the items
      included in the questionnaire was assessed by an expert panel of 10 nursing home
      care staff, because the questionnaire has not been used in this context
      previously. A psychometric evaluation using statistical estimates of validity and
      reliability was performed. The discriminatory capacity of the questionnaire was
      also tested. RESULTS: The content validity index was satisfactory (0.78). The PCQ
      S showed high internal consistency reliability in that Cronbach's alpha was
      satisfactory for the total scale (0.92) and the three subscales (0.81, 0.89 and
      0.87). The test-retest reliability was also satisfactory as evident from a
      Spearman's correlation coefficient of 0.76 (p < 0.01) between the total PCQ
      scores at test and retest. The Norwegian version retained the original factor
      structure of the Swedish version. CONCLUSION: As the psychometric evaluation
      showed satisfactory validity and reliability scores, this study supports the
      Norwegian version of the PCQ-S when applied to a sample of nursing home staff.

PMID- 22380608
TI  - Immune etiology of recurrent pregnancy loss and its diagnosis.
AB  - Recurrent Spontaneous Abortion of Immunological Origin (RSAI) is currently
      diagnosed by the occurrence of 2-3 consecutive miscarriages of unknown origin.
      The psychological trauma incurred by these events is a serious ailment which may
      be potentially avoided if a method of analysis is derived which may forecast
      these events and in turn prevent them from occurring. This review intends to
      examine studies of recurrent spontaneous abortion (RSA) which use laboratory
      diagnosis and also studies of RSA that do not use laboratory diagnosis. We
      believe that when laboratory results are incorporated into the diagnosis of
      RSA/RSAI that treatment is highly successful whereas the absence of laboratory
      results severely hinders the effectiveness of treatment. It is worth noting that
      correlating treatment versus outcome is imprudent because of the multiple
      variables involved in patient cases. It is not imprudent, however, to say that
      incorporation of laboratory data is essential when diagnosing RSA/RSAI.

PMID- 22380609
TI  - Single follicular unit transplantation reconstructs arrector pili muscle and
      nerve connections and restores functional hair follicle piloerection.
AB  - The autologous transplantation of hair follicles that have been separated into
      single follicular units is an accepted treatment for androgenetic alopecia.
      Recent studies demonstrate that the multiple stem cell populations and
      surrounding cutaneous tissues coordinately regulate the hair follicle functions
      and skin homeostasis. Therefore, the critical issues for consideration regarding
      functional hair restoration therapy are reproduction the correct connectivity and
      cooperation with host cutaneous tissues, including the arrector pili muscle (APM)
      and nerve system. We report successful establishment of mouse single follicular
      transplantation model and autonomous restoration of transplanted hair follicle
      piloerection in mouse skin. Transplanted hair follicles were responsive to the
      neurotransmitter acetylcholine and formed proper connections with surrounding
      host tissues such as APM and nerve fibers, which in turn connect with not only
      the hair follicle bulge region but also the APM. These results demonstrate that
      the piloerection ability of transplanted hair follicles can be estimated
      quantitatively. This study makes a substantial contribution towards the
      development of transplantation therapy that will facilitate future functional
      regeneration therapy for skin and skin appendages.

PMID- 22380610
TI  - Hydration of proteins: excess partial volumes of water and proteins.
AB  - High precision densitometry was applied to study the hydration of proteins. The
      hydration process was analyzed by the simultaneous monitoring of the excess
      partial volumes of water and the proteins in the entire range of water content.
      Five unrelated proteins (lysozyme, chymotrypsinogen A, ovalbumin, human serum
      albumin, and beta-lactoglobulin) were used as models. The obtained data were
      compared with the excess partial enthalpies of water and the proteins. It was
      shown that the excess partial quantities are very sensitive to the changes in the
      state of water and proteins. At the lowest water weight fractions (w(1)), the
      changes of the excess functions can mainly be attributed to water addition. A
      transition from the glassy to the flexible state of the proteins is accompanied
      by significant changes in the excess partial quantities of water and the
      proteins. This transition appears at a water weight fraction of 0.06 when charged
      groups of proteins are covered. Excess partial quantities reach their fully
      hydrated values at w(1) > 0.5 when coverage of both polar and weakly interacting
      surface elements is complete. At the highest water contents, water addition has
      no significant effect on the excess quantities. At w(1) > 0.5, changes in the
      excess functions can solely be attributed to changes in the state of the
      proteins.

PMID- 22380611
TI  - Mutations of complement lectin pathway genes MBL2 and MASP2 associated with
      placental malaria.
AB  - BACKGROUND: Innate immunity plays a crucial role in the host defense against
      malaria including Plasmodium falciparum malaria in pregnancy, but the roles of
      the various underlying genes and mechanisms predisposing to the disease are
      poorly understood. METHODS: 98 single-nucletoide polymorphisms were genotyped in
      a set of 17 functionally related genes of the complement system in 145
      primiparous Ghanaian women with placental malaria, defined by placental
      parasitaemia or malaria pigment, and as a control, in 124 non-affected
      primiparae. RESULTS: Placental malaria was significantly associated with SNPs in
      the lectin pathway genes MBL2, MASP2, FCN2 and in properdin. In particular, the
      main African mannose-binding lectin deficiency variant (MBL2*G57E, rs1800451)
      increased the odds of placental malaria (OR 1.6; permuted p-value 0.014). In
      contrast, a common MASP2 mutation (R439H, rs12085877), which reduces the activity
      of MBL-MASP2 complexes occurred in 33% of non-affected women and in 22%
      primiparae with placental malaria (OR 0.55, permuted p-value 0.020). CONCLUSIONS:
      Excessive complement activation is of importance in the pathogenesis of placental
      malaria by mediating inflammation, coagulation, and endothelial dysfunction.
      Mutated MBL and MASP2 proteins could have direct intrinsic effects on the
      susceptibility to placental malaria, in addition to their roles in regulation of
      downstream complement activation.

PMID- 22380612
TI  - Cyclic adenosine monophosphate metabolism in synaptic growth, strength, and
      precision: neural and behavioral phenotype-specific counterbalancing effects
      between dnc phosphodiesterase and rut adenylyl cyclase mutations.
AB  - Two classic learning mutants in Drosophila, rutabaga (rut) and dunce (dnc), are
      defective in cyclic adenosine monophosphate (cAMP) synthesis and degradation,
      respectively, exhibiting a variety of neuronal and behavioral defects. We ask how
      the opposing effects of these mutations on cAMP levels modify subsets of
      phenotypes, and whether any specific phenotypes could be ameliorated by
      biochemical counter balancing effects in dnc rut double mutants. Our study at
      larval neuromuscular junctions (NMJs) demonstrates that dnc mutations caused
      severe defects in nerve terminal morphology, characterized by unusually large
      synaptic boutons and aberrant innervation patterns. Interestingly, a
      counterbalancing effect led to rescue of the aberrant innervation patterns but
      the enlarged boutons in dnc rut double mutant remained as extreme as those in
      dnc. In contrast to dnc, rut mutations strongly affect synaptic transmission.
      Focal loose-patch recording data accumulated over 4 years suggest that synaptic
      currents in rut boutons were characterized by unusually large temporal dispersion
      and a seasonal variation in the amount of transmitter release, with diminished
      synaptic currents in summer months. Experiments with different rearing
      temperatures revealed that high temperature (29-30 degrees C) decreased synaptic
      transmission in rut, but did not alter dnc and wild-type (WT). Importantly, the
      large temporal dispersion and abnormal temperature dependence of synaptic
      transmission, characteristic of rut, still persisted in dnc rut double mutants.
      To interpret these results in a proper perspective, we reviewed previously
      documented differential effects of dnc and rut mutations and their genetic
      interactions in double mutants on a variety of physiological and behavioral
      phenotypes. The cases of rescue in double mutants are associated with gradual
      developmental and maintenance processes whereas many behavioral and physiological
      manifestations on faster time scales could not be rescued. We discuss factors
      that could contribute to the effectiveness of counterbalancing interactions
      between dnc and rut mutations for phenotypic rescue.

PMID- 22380613
TI  - Abdominal radical trachelectomy for treatment of deep infiltrating endometriosis
      of the cervix.
AB  - Surgical management of deep infiltrating endometriosis can be very challenging
      even for experienced gynecologists. Radical procedures like bowel resection and
      nephrectomy have been reported for treatment of the disease. Our aim is to report
      abdominal radical trachelectomy for treatment of deep infiltrating endometriosis
      of the cervix causing obstructive uropathy and diminished kidney function. We
      present a 38-year-old woman who was treated in our department for cervical
      endometriosis involving the vagina and left parametrium. Abdominal radical
      trachelectomy, insertion of a pig-tail catheter in the left ureter and end-to-end
      anastomosis of the uterus with the vagina was performed to remove the
      endometriotic lesion. Cooperation between gynecologists, urologists and
      nephrologists enabled fertility preservation as well as improvement of renal
      function. Deep infiltrating endometriosis is a complex disease that requires a
      multidisciplinary approach. Abdominal radical trachelectomy for cervical lesions
      seems feasible in this setting and helps preserve fertility.

PMID- 22380614
TI  - The impact of temperature on the inactivation of enteric viruses in food and
      water: a review.
AB  - Temperature is considered as the major factor determining virus inactivation in
      the environment. Food industries, therefore, widely apply temperature as virus
      inactivating parameter. This review encompasses an overview of viral inactivation
      and virus genome degradation data from published literature as well as a
      statistical analysis and the development of empirical formulae to predict virus
      inactivation. A total of 658 data (time to obtain a first log(10)  reduction)
      were collected from 76 published studies with 563 data on virus infectivity and
      95 data on genome degradation. Linear model fitting was applied to analyse the
      effects of temperature, virus species, detection method (cell culture or
      molecular methods), matrix (simple or complex) and temperature category (<50 and
      >=50 degrees C). As expected, virus inactivation was found to be faster at
      temperatures >=50 degrees C than at temperatures <50 degrees C, but there was
      also a significant temperature-matrix effect. Virus inactivation appeared to
      occur faster in complex than in simple matrices. In general, bacteriophages PRD1
      and PhiX174 appeared to be highly persistent whatever the matrix or the
      temperature, which makes them useful indicators for virus inactivation studies.
      The virus genome was shown to be more resistant than infectious virus. Simple
      empirical formulas were developed that can be used to predict virus inactivation
      and genome degradation for untested temperatures, time points or even virus
      strains.

PMID- 22380616
TI  - Long-term survival in a patient with amyotrophic lateral sclerosis and
      respiratory presentation.

PMID- 22380617
TI  - Sural nerve involvement in experimental hypertension: morphology and morphometry
      in male and female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive
      rats (SHR).
AB  - BACKGROUND: The sural nerve has been widely investigated in experimental models
      of neuropathies but information about its involvement in hypertension was not yet
      explored. The aim of the present study was to compare the morphological and
      morphometric aspects of different segments of the sural nerve in male and female
      spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats
      aged 20 weeks (N = 6 in each group) were investigated. After arterial pressure
      and heart rate recordings in anesthetized animals, right and left sural nerves
      were removed and prepared for epoxy resin embedding and light microscopy.
      Morphometric analysis was performed with the aid of computer software, and took
      into consideration the fascicle area and diameter, as well as myelinated fiber
      number, density, area and diameter. RESULTS: Significant differences were
      observed for the myelinated fiber number and density, comparing different genders
      of WKY and SHR. Also, significant differences for the morphological (thickening
      of the endoneural blood vessel walls and lumen reduction) and morphometric
      (myelinated fibers diameter and G ratio) parameters of myelinated fibers were
      identified. Morphological exam of the myelinated fibers suggested the presence of
      a neuropathy due to hypertension in both SHR genders. CONCLUSIONS: These results
      indicate that hypertension altered important morphometric parameters related to
      nerve conduction of sural nerve in hypertensive animals. Moreover the comparison
      between males and females of WKY and SHR allows the conclusion that the
      morphological and morphometric parameters of sural nerve are not gender related.
      The morphometric approach confirmed the presence of neuropathy, mainly associated
      to the small myelinated fibers. In conclusion, the present study collected
      evidences that the high blood pressure in SHR is affecting the sural nerve
      myelinated fibers.

PMID- 22380618
TI  - Expression of "a disintegrin and metalloproteinase-33" (ADAM-33) protein in
      laryngeal squamous cell carcinoma.
AB  - OBJECTIVE: A disintegrin and metalloproteinase domain containing protein 33 (also
      known as ADAM-33) is a member of a matrix metalloproteinase family which mediates
      extracellular matrix remodelling and changes in cellular adhesion. This study
      aimed to evaluate expression of this protein in laryngeal squamous cell
      carcinoma, and to determine its correlation with patients' clinicopathological
      characteristics. SUBJECTS AND METHODS: Forty paraffin blocks of laryngeal
      carcinoma underwent immunohistochemical staining to detect "a disintegrin and
      metalloproteinase-33" expression. Case records were reviewed to determine patient
      characteristics. RESULTS: All epithelial, vascular and stromal staining scores
      were significantly increased in tumour tissue compared with controls (p < 0.001).
      However, patients' clinical characteristics at the time of diagnosis, and their
      disease extent, did not correlate significantly with the immunohistochemical
      staining scores. CONCLUSION: This study suggests that increased expression of "a
      disintegrin and metalloproteinase-33" may play a role in the pathogenesis of
      laryngeal carcinoma.

PMID- 22380619
TI  - The objective-subjective assessment of noise: young adults can estimate loudness
      of events and lifestyle noise.
AB  - OBJECTIVE: The aim of the study was to establish whether individuals can
      subjectively estimate: (1) the loudness of events with respect to the objectively
      measured noise level; and (2) the overall loudness of their daily noise exposure
      level. DESIGN: Participants wore personal noise exposure meters for up to five
      days. During this time, participants kept diaries of daily events and estimated
      the loudness of these events and their overall noise exposure using 1-to-10
      rating scales. STUDY SAMPLE: A group of 45 volunteers aged between 18 and 35
      years participated in the study. RESULTS: 86% of participants' subjective
      estimates were significantly correlated with the objective noise measurements.
      Multiple regression showed that age, overall lifestyle noise, and diary quality
      were predictors of the strength of correlation observed. In addition
      participants' subjective estimates of their overall noise exposure were
      significantly correlated with their actual average daily noise exposure.
      CONCLUSIONS: Results suggest that individuals can make a reasonable estimate of
      the loudness of events they experience and the overall level of noise they
      experience. These results may have significant influence for those interested in
      producing effective hearing health awareness programs in that individuals may be
      capable of assessing their own degree of hazard exposure.

PMID- 22380621
TI  - On the gas-phase Co(+)-mediated oxidation of ethane by N2O: a mechanistic study.
AB  - The potential energy surface (PES) corresponding to the Co(+)-mediated oxidation
      of ethane by N(2)O has been investigated by using density functional theory
      (DFT). After initial N(2)O reduction by Co(+) to CoO(+), ethane oxidation by the
      nascent oxide involves C-H activation followed by two possible pathways, i.e., C
      O coupling accounting for ethanol, Co(+)-mediated beta-H shift giving the
      energetically favorable product of CoC(2)H(4)(+) + H(2)O, with minor CoOH(2)(+) +
      C(2)H(4). CoC(2)H(4)(+) could react with another N(2)O to yield (C(2)H(4))Co(+)O,
      which could subsequently undergo a cyclization mechanism accounting for
      acetaldehyde and oxirane and/or a direct H-abstraction mechansim for ethenol.
      Loss of oxirane and ethenol is hampered by respective endothermicity and high
      kinetics barrier, whereas acetaldehyde elimination is much energetically
      favorable. CoOH(2)(+) could facilely react with N(2)O to form OCoOH(2)(+), rather
      than Co(OH)(2)(+) or CoO(+).

PMID- 22380620
TI  - Retinoic acid mediates the expression of glutamate transporter-1 in rat
      astrocytes through genomic RXR action and non-genomic protein kinase C signaling
      pathway.
AB  - Astrocytic glutamate transporter-1 (GLT-1) is responsible for 90% of forebrain
      glutamate uptake in the adult CNS. Retinoic acid (RA) is a potent regulator of
      neural cell differentiation and neuronal maturation in the developing CNS through
      activation of RA receptors/retinoic X receptors (RXRs) or non-genomic mechanisms.
      Although rat GLT-1 contains several RXR binding regions, RA-triggered RXR
      mechanisms regulating GLT-1 expression remain unknown. RA applied at
      submicromolar concentrations for 24 h significantly reduced GLT-1 mRNA and
      membrane levels in astrocytes and dibutyryl cAMP (dbcAMP)-primed astrocytes. An
      RXR agonist reduced astrocytic GLT-1 mRNA expression, whereas an RXR antagonist
      blocked the effects of RA on the reduction of astrocytic GLT-1 mRNA expression.
      Electrophoresis motility shift assay indicated that RA-treatment increased
      astrocytic RXR-DNA binding activity. RA-induced reduction in GLT-1 mRNA
      expression was also observed in dbcAMP-primed astrocytes. Through lentivirus
      mediated astrocytic over-expression of rat GLT-1, levels of GLT-1 in the
      processes of dbcAMP-treated astrocytes were attenuated by exposure to RA. The
      protein kinase C inhibitor, Bis I, restored GLT-1 distribution in the processes
      of RA-treated dbcAMP-primed astrocytes. These results suggest that RA reduces
      astrocytic GLT-1 levels through both RXR-mediated inhibition at the
      transcriptional level and triggering activation of protein kinase C which reduces
      cell surface GLT-1 levels.

PMID- 22380622
TI  - The lp13.3 genomic region -rs599839- is associated with endothelial dysfunction
      in patients with rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an inflammatory disease associated
      with accelerated atherosclerosis and high risk of cardiovascular (CV) disease.
      Since genome-wide association studies demonstrated association between rs599839
      polymorphism and coronary artery disease, in the present study we assessed the
      potential association of this polymorphism with endothelial dysfunction, an early
      step in atherogenesis. METHODS: A total of 128 RA patients without history of CV
      events were genotyped for rs599839 A/G polymorphism. The presence of endothelial
      dysfunction was assessed by brachial ultrasonography (brachial flow-mediated
      endothelium-dependent (FMD)). RESULTS: Patients carrying the allele G exhibited
      more severe endothelial dysfunction (FMD%: 4.61 +/- 3.94%) than those carrying
      the wild allele A (FMD%: 6.01 +/- 5.15%) (P = 0.08). Adjustment for gender, age
      at the time of study, follow-up time and classic CV risk factors disclosed a
      significant association between the rs599839 polymorphism and FMD (G vs. A: P =
      0.0062). CONCLUSIONS: Our results confirm an association of the rs599839
      polymorphism with endothelial dysfunction in RA.

PMID- 22380623
TI  - An antidote for acute cocaine toxicity.
AB  - Not only has immunopharmacotherapy grown into a field that addresses the abuse of
      numerous illicit substances, but also the treatment methodologies within
      immunopharmacotherapy have expanded from traditional active vaccination to
      passive immunization with anti-drug monoclonal antibodies, optimized mAb formats,
      and catalytic drug-degrading antibodies. Many laboratories have focused on
      transitioning distinct immunopharmacotherapeutics to clinical evaluation, but
      with respect to the indication of cocaine abuse, only the active vaccine TA-CD,
      which is modeled after our original cocaine hapten GNC, has been carried through
      to human clinical trials. The successful application of murine mAb GNC92H2 to the
      reversal of cocaine overdose in a mouse model prompted investigations of human
      immunoglobulins with the clinical potential to serve as cocaine antidotes. We now
      report the therapeutic utility of a superior clone, human mAb GNCgzk (K(d) = 0.18
      nM), which offers a 10-fold improvement in cocaine binding affinity. The GNCgzk
      manifold was engineered for rapid cocaine clearance, and administration of the
      F(ab')2 and Fab formats even after the appearance of acute behavioral signs of
      cocaine toxicity granted nearly complete prevention of lethality. Thus, contrary
      to the immunopharmacotherapeutic treatment of drug self-administration, minimal
      antibody doses were shown to counteract the lethality of a molar excess of
      circulating cocaine. Passive vaccination with drug-specific antibodies represents
      a viable treatment strategy for the human condition of cocaine overdose.

PMID- 22380624
TI  - Phototropism and gravitropism in transgenic lines of Arabidopsis altered in the
      phytochrome pathway.
AB  - Phytochromes are a family of photoreceptor molecules, absorbing primarily in red
      and far-red, that are important in many aspects of plant development. These
      studies investigated the role of phytochromes in phototropism and gravitropism of
      seedlings of Arabidopsis thaliana. We used two transgenic lines, one which lacked
      phytochromes specifically in the roots (M0062/UASBVR) and the other lacked
      phytochromes in the shoots (CAB3::pBVR). These transgenic plants are deficient in
      the phytochrome chromophore in specific tissues due the expression of biliverdin
      IXa reductase (BVR), which binds to precursors of the chromophore. Experiments
      were performed in both light and dark conditions to determine whether roots
      directly perceive light signals or if the signal is perceived in the shoot and
      then transmitted to the root during tropistic curvature. Kinetics of tropisms and
      growth were assayed by standard methods or with a computer-based feedback system.
      We found that the perception of red light occurs directly in the root during
      phototropism in this organ and that signaling also may occur from root to shoot
      in gravitropism.

PMID- 22380625
TI  - Application of electrochemically reduced graphene oxide on screen-printed ion
      selective electrode.
AB  - In this study, a novel disposable all-solid-state ion-selective electrode using
      graphene as the ion-to-electron transducer was developed. The graphene film was
      prepared on screen-printed electrode directly from the graphene oxide dispersion
      by a one-step electrodeposition technique. Cyclic voltammetry and electrochemical
      impedance spectroscopy were employed to demonstrate the large double layer
      capacitance and fast charge transfer of the graphene film modified electrode. On
      the basis of these excellent properties, an all-solid-state calcium ion-selective
      electrode as the model was constructed using the calcium ion-selective membrane
      and graphene film modified electrode. The mechanism about the graphene promoting
      the ion-to-electron transformation was investigated in detail. The disposable
      electrode exhibited a Nernstian slope (29.1 mV/decade), low detection limit (10(
      5.8) M), and fast response time (less than 10 s). With the high hydrophobic
      character of graphene materials, no water film was formed between the ion
      selective membrane and the underlying graphene layer. Further studies revealed
      that the developed electrode was insensitive to light, oxygen, and redox species.
      The use of the disposable electrode for real sample analysis obtained
      satisfactory results, which made it a promising alternative in routine sensing
      applications.

PMID- 22380626
TI  - The Persian version of the Berg Balance Scale: inter and intra-rater reliability
      and construct validity in elderly adults.
AB  - PURPOSE: As a well-known measure for quantifying functional mobility in elderly
      persons, Berg Balance Scale (BBS) was used in the present study to evaluate its
      psychometric properties among a sample of 106 elderly individuals speaking
      Persian language. METHOD: After forward-backward translation process, videotapes
      were recorded from all participants while performing 14 tasks of the BBS. The
      volunteers were also asked to perform the Timed Up and Go (TUG) test at the same
      session. To determine inter and intra-rater reliability, the videotapes were
      viewed by two experienced therapists while one of the raters assessed the
      videotaped performance of the subjects on a second occasion. RESULTS: Intraclass
      correlation coefficients (95% confidence interval) of 0.93 (0.87 0.96) and 0.95
      (0.92 0.97) were obtained for inter and intra-rater reliability, respectively.
      Cronbach's alpha was 0.62 which is marginally lower than the cut-off point of
      0.70. Furthermore, there were no ceiling and floor effects for the Persian
      version. In terms of construct validity, the BBS had a negative and strong
      correlation with the TUG (r = -0.74, p < 0.001). CONCLUSIONS: Acceptable levels
      of intra and inter-rater reliability with a moderate internal consistency and
      high validity were demonstrated for the Persian version of BBS.

PMID- 22380627
TI  - The role of cognition in cost-effectiveness analyses of behavioral interventions.
AB  - BACKGROUND: Behavioral interventions typically focus on objective behavioral
      endpoints like weight loss and smoking cessation. In reality, though, achieving
      full behavior change is a complex process in which several steps towards success
      are taken. Any progress in this process may also be considered as a beneficial
      outcome of the intervention, assuming that this increases the likelihood to
      achieve successful behavior change eventually. Until recently, there has been
      little consideration about whether partial behavior change at follow-up should be
      incorporated in cost-effectiveness analyses (CEAs). The aim of this explorative
      review is to identify CEAs of behavioral interventions in which cognitive outcome
      measures of behavior change are analyzed. METHODS: Data sources were searched for
      publications before May 2011. RESULTS: Twelve studies were found eligible for
      inclusion. Two different approaches were found: three studies calculated separate
      incremental cost-effectiveness ratios for cognitive outcome measures, and one
      study modeled partial behavior change into the final outcome. Both approaches
      rely on the assumption, be it implicitly or explicitly, that changes in cognitive
      outcome measures are predictive of future behavior change and may affect CEA
      outcomes. CONCLUSION: Potential value of cognitive states in CEA, as a way to
      account for partial behavior change, is to some extent recognized but not (yet)
      integrated in the field. In conclusion, CEAs should consider, and where
      appropriate incorporate measures of partial behavior change when reporting
      effectiveness and hence cost-effectiveness.

PMID- 22380628
TI  - Multiple pregnancy failures: an immunological paradigm.
AB  - Recurrent spontaneous abortion (RSA), three or more pregnancy losses prior to 20
      weeks, occurs in about 1% of all pregnancies, 50% of RSA cases remain unexplained
      and unresolved. Recently, immune pathways have been implicated in the
      pathophysiology of RSA. Immune tolerance of the fetal-placental unit and
      placental angiogenesis are mandatory for a successful pregnancy outcome.
      Unscheduled dysregulation of the placental vasculature is thought to be the
      pathophysiologic mechanisms underlying an array of pregnancy complications like
      infertility, miscarriage, pre-eclampsia, and fetal growth restriction and death.
      Investigations on mechanisms and management of RSA are mired by substandard
      design and lack of optimal randomized clinical trials and have resulted in
      disagreement on guidelines for evaluation and treatments for patients with
      multiple pregnancy losses of unknown etiology. The present review focuses on
      evidence-based research discussion with immunologic causes, and immune-regulatory
      therapies recommended for helping patients with a history of RSA. We highlight
      data that might support revalidation of low molecular weight heparin as a
      protective therapy in RSA. Newly launched growth factors, GM-CSF, and potentially
      novel agents to suppress inflammatory rejection, including regulatory T cells,
      human chorionic gonadotropin, and M-CSF/IL-10, may work in concert with tender
      loving-care therapy and give hope to couples with multiple pregnancy losses.

PMID- 22380629
TI  - Discovery of cyclic sulfone hydroxyethylamines as potent and selective beta-site
      APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo
      reduction of amyloid beta-peptides.
AB  - Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors
      allowed the rational incorporation of prime- and nonprime-side fragments to a
      central core template without any amide functionality. The core scaffold
      selection and the structure-activity relationship development were supported by
      molecular modeling studies and by X-ray analysis of BACE1 complexes with various
      ligands to expedite the optimization of the series. The direct extension from P1
      aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement
      of potency and selectivity over cathepsin D. Restraining the design and synthesis
      of compounds to a physicochemical property space consistent with central nervous
      system drugs led to inhibitors with improved blood-brain barrier permeability.
      Guided by structure-based optimization, we were able to obtain highly potent
      compounds such as 60p with enzymatic and cellular IC(50) values of 2 and 50 nM,
      respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic
      studies in APP51/16 transgenic mice at oral doses of 180 MUmol/kg demonstrated
      significant reduction of brain Abeta levels.

PMID- 22380630
TI  - Different median levels of serum triple markers in the second trimester of
      pregnancy in a Thai Ethnic Group.
AB  - AIM: The aim of the present study was to establish Thai-specific reference ranges
      of triple markers for fetal Down syndrome as a function of gestational age as
      well as weight correction models and to compare the false positive rates when
      using Thai-specific model relative to Caucasian-specific model. MATERIAL AND
      METHODS: A total of 993 normal Thai pregnant women were determined for mid
      trimester serum levels of alpha-fetoprotein (AFP), free-beta human chorionic
      gonadotropin (hCG), and unconjugated estriol (uE3), using DefiaXpress system
      (Perkin Elmer, Waltham, MA, USA). RESULTS: The models of Thai-specific medians
      for AFP, b-hCG, and uE3, as well as the models for weight correction were derived
      and the normal reference ranges were constructed. The best fitted equation for
      AFP, b-hCG and uE3 are as follows: predicted median = 2.675 * 10((0.153 * GA in
      week)), r = 0.979; 10((-0.717 + 57.487/GA in week)) , r = 0.991; and 10((5.678
      69.346/GA) (in) (week)), r = 0.99, respectively. The models were properly applied
      to another group of 302 Thai women, signifying that they were reliable models.
      The weight-adjusted gestation-specific medians derived from Caucasian models were
      significantly higher than those based on Thai models and the false positive rate
      could be reduced from 10 to 7.1% when Thai models were applied. CONCLUSION: Thai
      reference ranges of triple screen markers as a function of gestational age as
      well as weight correction models have been established. The Caucasian reference
      range, even after weight correction, gives a positive rate that is much higher
      than that it should be, strongly suggesting the need for ethnicity-specific
      medians.

PMID- 22380631
TI  - Isolation and identification of new inner membrane-associated proteins that
      localize to cell poles in Escherichia coli.
AB  - Several bacterial structures, processes and proteins are localized primarily to
      the poles of rod-shaped cells. To better understand this cellular organization,
      we devised a new method for identifying proteins that localize to the poles of
      Escherichia coli. Pole-derived membrane fragments were isolated by affinity
      capture of vesicles containing the chemotaxis protein, Tar; and for comparison,
      vesicles representing all parts of the cytoplasmic membrane were captured by
      expressing a Tar variant that was no longer pole-specific. A combination of one
      dimensional SDS-PAGE and semi-quantitative mass spectrometry identified 31
      proteins that were highly enriched in polar vesicles. Five were chemotaxis
      proteins known to be pole-specific and another, Aer, was an aerotaxis protein
      that had not yet been localized to the pole. The behaviour of these internal
      controls validated the overall approach. GFP-fused derivatives of four candidates
      (Aer, YqjD, TnaA and GroES) formed polar foci that were distinct from inclusion
      bodies. TnaA-GFP and GroES-GFP were functional, formed a single focus per cell,
      and competed for polar localization with the wild-type versions of these
      proteins. Polar localization of TnaA, GroES and YqjD was disrupted in cells
      lacking the MinCDE proteins, suggesting that this system may help localize
      proteins not involved in cell division.

PMID- 22380632
TI  - Comparison of the effects of maxillary protraction using facemask and miniplate
      anchorage between unilateral and bilateral cleft lip and palate patients.
AB  - OBJECTIVE: To determine the difference in the effects of facemask with miniplate
      (FM-MP) anchorage on maxillary protraction in growing cleft patients between
      unilateral (UCLP) and bilateral cleft lip and palate (BCLP) groups. MATERIALS AND
      METHODS: The samples consisted of a UCLP group (N  =  15, 13 boys and 2 girls;
      mean age 10.98 years; mean protraction duration 2.37 years) and a BCLP group (N 
      =  15, all boys; mean age 11.42 years; mean protraction duration 2.36 years), who
      were treated with the same surgical technique (rotation and advancement flap and
      double opposing Z-plasty) by one surgeon and with FM-MP by one orthodontist.
      Lateral cephalograms were taken before (T1) and after FM-MP (T2). Fourteen
      skeletal and dental variables were measured. Independent and paired t-tests were
      performed for statistical analysis. RESULTS: There were no differences in mean
      age and values of variables at the T1 stage and in the duration of protraction
      between the two groups. The BCLP group showed less advancement of point A than
      the UCLP group (DeltaA-vertical reference plane, 2.51 mm vs 4.06 mm, P < .05;
      DeltaA-N perpendicular, 0.79 mm vs 2.26 mm, P < .05; DeltaSNA, 0.45 degrees  vs
      2.85 degrees , P < .01). Since counterclockwise rotation of the palatal plane in
      two groups was minimal (-0.36 degrees  vs -0.87 degrees ), no difference was
      observed with regard to clockwise rotation of the mandible (0.46 degrees  vs 
      0.07 degrees ). There were no differences in the degree of labioversion of the
      maxillary incisor (8.16 degrees  vs 7.10 degrees ), linguoversion of the
      mandibular incisor (-2.66 degrees  vs -2.14 degrees ), and increase in overjet
      (5.39 mm vs 5.70 mm) between the two groups. CONCLUSION: In FM-MP therapy of
      growing cleft patients under the conditions of this study, the UCLP group shows a
      more favorable change in maxillary advancement than the BCLP group.

PMID- 22380633
TI  - Oral health status of elderly hospitalised psychiatric patients.
AB  - OBJECTIVES: This study investigated the oral health status of an elderly mentally
      ill population hospitalised in a psychogeriatric ward in Athens. MATERIALS AND
      METHODS: A structured interview recorded sociodemographic and dental data, and an
      oral examination recorded the status of oral tissues and the existing dentures.
      The patients' medical records were examined by a hospital's physician. RESULTS:
      One hundred and eleven patients with a mean age of 73 years participated in the
      study. Almost half of them suffered from schizophrenia. Forty percent were
      completely edentulous but only 38.6% of them used a pair of dentures. The dentate
      had an average of 12.9 teeth, 50.7% of them had at least one decayed tooth, 44.8%
      needed at least one extraction, and only 26.7% had filled teeth. The dental
      hygiene was poor in 83.6% of the patients. More than 60% of the dentures had a
      defect. Multiple regression analyses showed that increasing age and dementia were
      significantly related to fewer remaining teeth, and the use of atypical
      antipsychotics was related to fewer caried teeth. CONCLUSION: The oral health of
      the elderly psychiatric patients was very poor. Access to dental care should
      improve, and the health care staff should be trained to identify oral problems.

PMID- 22380634
TI  - Chitosan: antimicrobial action upon staphylococci after impregnation onto cotton
      fabric.
AB  - BACKGROUND: High levels of viable Staphylococcus aureus, which are often found on
      inflamed skin surfaces, are usually associated with atopic dermatitis. Textiles,
      owing to their high specific surface area and intrinsic hydrophilicity, retain
      moisture while also providing excellent environmental conditions for microbial
      growth and proliferation. Recently, a number of chemicals have been added to
      textiles, so as to confer antimicrobial activity. AIMS: To evaluate the
      antimicrobial action of chitosan upon selected skin staphylococci. METHODS AND
      RESULTS: We isolated staphylococci from normal skin of 24 volunteers and studied
      their survival upon contact with chitosan-impregnated cotton fabric. Low and high
      molecular weight chitosans were used at two concentrations; all four did
      effectively reduce the growth of some staphylococci (namely Staph. aureus), by up
      to 5 log cycles, thus unfolding a potential towards control and even prevention
      of related skin disorders. CONCLUSION: Our data suggest an effective, but
      selective antibacterial action of chitosans towards skin bacteria. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The possibility to use a natural biopolymer incorporated
      in a textile to alleviate and even treat some of the symptoms associated with
      this skin condition may raise an alternative to existing medical treatments. The
      selectivity observed prevents full elimination of bacteria from the skin surface,
      which is an advantage.

PMID- 22380635
TI  - Endoscopic, assisted, modified turbinoplasty with mucosal flap.
AB  - A variety of surgical methods have been developed to reduce the volume of the
      inferior turbinates, in order to create a more patent nasal airway. We describe a
      technique used in our department since February 2002 for all patients undergoing
      inferior turbinectomy. We resect with endoscopic assistance the lateral mucosa
      and bony inferior turbinate. This technique can reduce a large volume of the
      turbinate while preserving the mucosal continuity and the submucosa by covering
      the raw surface with a mucosal flap. We believe our method minimises post
      operative side effects and complications such as dryness, infection, bleeding and
      pain.

PMID- 22380636
TI  - Key role of microbial characteristics on the performance of VOC biodegradation in
      two-liquid phase bioreactors.
AB  - Despite being studied for over 20 years, little is known about the mechanisms
      underlying the treatment of volatile organic compounds (VOCs) from industrial off
      gases in two-liquid phase bioreactors (TLPBs). Recent reports have highlighted a
      significant mismatch between the high abiotic mass transfer capacity of TLPBs and
      the low VOC biodegradation rates sometimes recorded, which suggests that a
      process limitation might also be found in the microbiology of the process.
      Therefore, this study was conducted to assess the key role of microbial
      characteristics on the performance of VOC biodegradation in a TLPB using three
      different hexane degrading consortia. When silicone oil 200 cSt (SO200) was added
      to the systems, the steady state hexane elimination capacities (ECs) increased by
      a factor of 8.7 and 16.3 for Consortium A (hydrophilic microorganisms) and B
      (100% hydrophobic microorganisms), respectively. In the presence of SO200,
      Consortium C supported a first steady state with a 2-fold increase in ECs
      followed by a 16-fold EC increase after a hydrophobicity shift (to 100%
      hydrophobic microorganisms), compared to the system deprived of SO200. This work
      revealed that cell hydrophobicity can play a key role in the successful
      performance of TLPBs, and to the best of our knowledge, this is the first report
      on hydrophobic VOC treatment with exclusive VOC uptake within a nonbioavailable
      non aqueous phase. Finally, an independent set of experiments showed that
      metabolite accumulation can also severely inhibit TLPB performance despite the
      presence of SO200.

PMID- 22380637
TI  - The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid
      hemorrhage.
AB  - Delayed cerebral ischemia resulting from extracellular hemoglobin is an important
      determinant of outcome in subarachnoid hemorrhage. Hemoglobin is scavenged by the
      CD163-haptoglobin system in the circulation, but little is known about this
      scavenging pathway in the human CNS. The components of this system were analyzed
      in normal cerebrospinal fluid and after subarachnoid hemorrhage. The intrathecal
      presence of the CD163-haptoglobin-hemoglobin scavenging system was unequivocally
      demonstrated. The resting capacity of the CD163-haptoglobin-hemoglobin system in
      the normal CNS was 50 000-fold lower than that of the circulation. After
      subarachnoid hemorrhage, the intrathecal CD163-haptoglobin-hemoglobin system was
      saturated, as shown by the presence of extracellular hemoglobin despite
      detectable haptoglobin. Hemoglobin efflux from the CNS was evident, enabling
      rescue hemoglobin scavenging by the systemic circulation. Therefore, the CNS is
      not capable of dealing with significant intrathecal hemolysis. Potential
      therapeutic options to prevent delayed cerebral ischemia ought to concentrate on
      augmenting the capacity of the intrathecal CD163-haptoglobin-hemoglobin
      scavenging system and strategies to encourage hemoglobin efflux from the brain.

PMID- 22380638
TI  - Working with Yoshiki. Two-dimensional gels and freeze-drying fruitfl ies.

PMID- 22380639
TI  - Striatal dopamine loss and discriminative sensory dysfunction in Parkinson's
      disease.
AB  - OBJECTIVES: Patients with Parkinson's disease (PD) have higher-order
      discriminative sensory dysfunction including prolonged somesthetic temporal
      discrimination threshold (sTDT). We studied the effect of striatal dopamine loss
      on the prolongation of sTDT and also studied the impact of prolonged sTDT values
      on the various parkinsonian motor deficits. MATERIALS AND METHODS: In 30 patients
      with PD, the severity of parkinsonian motor deficits was evaluated using the
      Unified Parkinson's Disease Rating Scale (UPDRS) motor scores during levodopa off
      and on periods. The UPDRS motor subscores were calculated, representing
      bradykinesia, rigidity, tremor, and axial motor deficits. During levodopa off and
      on periods, the sTDT value of each index finger was studied. Using [(18) F]-N-3
      fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FPCIT)
      positron emission tomography studies, caudate and putaminal dopamine transporter
      uptake levels were measured. Multiple regression analysis covariated with age was
      used for statistical analysis. RESULTS: During the off period, the striatal FPCIT
      uptake levels had an impact on the sTDT values (P < 0.01). The sTDT values had an
      impact on the UPDRS subscores for axial motor deficits (P < 0.05), but had no
      impact on those for bradykinesia, rigidity, and tremor. The sTDT values as well
      as UPDRS total motor scores and all UPDRS subscores were improved by a single
      oral levodopa treatment. CONCLUSIONS: Striatal dopamine deficiency and consequent
      basal ganglia dysfunction may prolong sTDT, and higher-order discriminative
      sensory dysfunction seems to contribute in part to the development of axial motor
      deficits in patients with PD.

PMID- 22380640
TI  - Vibrationally resolved LIF spectrum of tertiary methylcyclohexoxy radical.
AB  - Cyclohexoxy radical and its substitutes are intermediates of the combustion
      reaction in automobile engines, and hence play an important role in the
      atmospheric chemistry. Spectroscopic and conformational studies can provide
      convenient methods to monitor these species. In this work, we report the
      observation of the laser induced fluorescence (LIF) excitation spectrum of 1
      methylcyclohexoxy, a tertiary ring alkoxy radical, in supersonic jet condition.
      The spectrum was assigned preliminarily to the chair-axial and chair-equatorial
      conformers of 1-methylcyclohexoxy. No C-O stretch progression was observed in 1
      methylcyclohexoxy spectrum, which was different from t-butoxy. The short lifetime
      of excited state 1-methylcyclohexoxy and increased C-O bond length suggested a
      less stable excited state induced by the increased steric repulsion via methyl
      substitution on the alkoxy carbon. Dissociation rather than H transfer was
      suggested as the major nonradiative relaxation process, which competed with the
      fluorescence path.

PMID- 22380641
TI  - Mosuos' awareness of taxonomic relations in word associations, lexicon decisions
      and semantic categorizations.
AB  - The development of representations for taxonomic categories is influenced by many
      factors, such as age, life experiences, and education. It was hypothesized that
      Mosuos might be aware of taxonomic relations differently than Hans, as indicated
      by Sha (1996). Three experiments--word associations, lexicon decisions, and
      semantic categorizations--were conducted on young adults of Mosuos and Hans and
      consistent results were obtained: the Mosuos were found both similar to and
      different from the Hans in their experimental performance. They were apparently
      aware of taxonomic relations less than the Hans among categories of different
      levels and among categories of basic level, consistent with the conclusion that
      the uniqueness of a specific culture influences the people's representations for
      the hierarchically structured taxonomic categories (Lopez, Atran, Coley, Medin &
      Smith, 1997). The present forms of education did not seem to be as effective as
      educators expected to help promote Mosuo children's development of knowledge of
      taxonomic categories. If school education would be available that is compatible
      with the cultural value of a relatively isolated, small population, such as
      Mosuos, and is of practical value for the young children to develop a better
      knowledge of the world, then a study would be of critical value into how educated
      individuals would be different from uneducated ones in their awareness of
      taxonomic relations.

PMID- 22380642
TI  - Pharmacist counseling to cardiac patients in Israel prior to discharge from
      hospital contribute to increasing patient's medication adherence closing gaps and
      improving outcomes.
AB  - BACKGROUND: Medication non adherence is a global epidemic perplexing phenomenon
      that is eminent, but not insurmountable. Our first objective was to explore
      whether providing pharmacist's counseling to cardiac patients prior to discharge
      can increase patient's medication adherence, and our second objective was to
      assess whether better medication adherence leads to reduction of hospital
      readmissions. METHODS: Observational study was conducted among diagnosed cardiac
      patients using an intervention strategy at discharge from two hospitals in
      Israel; The Nazareth and the Haemek hospital. 74 patients were recruited between
      January 2010 and January 2011. Two separate groups were selected; intervention
      group: 33 patients who prior to discharge received nurse, pharmacist
      interventions, and control group: 41 patients who had received the nurse and
      hospital discharge counseling only. RESULTS: Regression analysis for examining
      the first objective reflected significant effect when having a pharmacist
      interventions, which explains the increasing 11.6% of the variance in medication
      adherence, [F change (1,73) = 9.43, p < 0.003]. Stepwise regression analysis for
      examining the second objective demonstrated that the relation between medication
      adherence and readmissions was insignificant [F (1,73) = 9.43, n.s]. CONCLUSIONS:
      While physicians and nurses can have an impact on improving adherence,
      pharmacists have demonstrated the ability to inform, problem-solve and provide
      performance support directly to patients.

PMID- 22380643
TI  - Laparoscopic excision of a large prostatic utricle revealed by haematuria: 1-year
      follow-up.
AB  - Prostatic utricles revealed by the presentation of haematuria are very rare. Only
      limited experience with laparoscopic surgery of prostatic utricle has been
      reported to date. Herein we report a 20-year-old male with frequently terminal
      haematuria and oligozoospermia who underwent successful laparoscopic excision of
      a large prostatic utricle. Haematuria disappeared and semen quality improved
      during 1-year follow-up.

PMID- 22380644
TI  - Now offering: Journal of Prosthodontics online continuing dental education.

PMID- 22380645
TI  - Elemental release from CoCr and NiCr alloys containing palladium.
AB  - PURPOSE: An entirely new subclass of casting alloy composition whereby palladium
      (~approximately 25 wt%) is added to traditional base metal alloys such as CoCr
      and NiCr was recently introduced to the market. The purpose of this study was to
      evaluate the elemental release of new CoPdCr and NiPdCr alloys and compare them
      to traditional CoCr and NiCr alloys. MATERIALS AND METHODS: Five casting alloys
      were investigated: CoPdCr-A (NobleCrown NF, The Argen Corporation), CoPdCr-I
      (Callisto CP+, Ivoclar Vivadent), NiPdCr (NobleCrown, Argen), CoCr (Argeloy N.P.
      Special, Argen), and NiCr (Argeloy N.P. Star, Argen). Rectangular specimens (n =
      6/alloy) were prepared and immersed in a lactic acid/NaCl solution at 37 degrees
      C for 7 days according to ISO 10271. Solutions were analyzed with ICP-AES to
      determine elemental release. The concentrations of major ions (cobalt, nickel,
      palladium, chromium, and molybdenum) were compared using a generalized linear
      model (p < 0.05). Representative specimens were examined with optical microscopy
      before and after immersion. RESULTS: The CoPdCr alloys released a significantly
      greater amount of respective ions (Co, Cr, Mo, and total ions) compared to the
      traditional CoCr alloy. No significant differences in elemental release were
      noted between NiPdCr and NiCr. Optical microscopic examination showed abundant
      areas of corrosion in the palladium-containing CoCr alloys after immersion,
      whereas little difference was observed for the other alloys. CONCLUSIONS:
      Corrosion resistance measured via elemental release was compromised when CoCr was
      alloyed with palladium, but this effect was not observed with NiCr.

PMID- 22380646
TI  - Color and luminescence stability of selected dental materials in vitro.
AB  - PURPOSE: To study luminescence, reflectance, and color stability of dental
      composites and ceramics. MATERIALS AND METHODS: IPS e.max, IPS Classic, Gradia,
      and Sinfony materials were tested, both unpolished (as-cast) and polished
      specimens. Coffee, tea, red wine, and distilled water (control) were used as
      staining drinks. Disk-shaped specimens were soaked in the staining drinks for up
      to 5 days. Color was measured by a colorimeter. Fluorescence was recorded using a
      spectrofluorometer, in the front-face geometry. Time-resolved fluorescence
      spectra were recorded using a laser nanosecond spectrofluorometer. RESULTS: The
      exposure of the examined dental materials to staining drinks caused changes in
      color of the composites and ceramics, with the polished specimens exhibiting
      significantly lower color changes as compared to unpolished specimens. Composites
      exhibited lower color stability as compared to ceramic materials. Water also
      caused perceptible color changes in most materials. The materials tested
      demonstrated significantly different initial luminescence intensities. Upon
      exposure to staining drinks, luminescence became weaker by up to 40%, dependent
      on the drink and the material. Time-resolved luminescence spectra exhibited some
      red shift of the emission band at longer times, with the lifetimes in the range
      of tens of nanoseconds. CONCLUSIONS: Unpolished specimens with a more developed
      surface have lower color stability. Specimens stored in water develop some
      changes in their visual appearance. The presently proposed methods are effective
      in evaluating the luminescence of dental materials. Luminescence needs to be
      tested in addition to color, as the two characteristics are uncorrelated. It is
      important to further improve the color and luminescence stability of dental
      materials.

PMID- 22380647
TI  - A technique for fabrication of an extracoronal attachment-retained removable
      partial denture to fit an existing fixed partial denture.
AB  - Precision attachments have been used for many years to retain removable partial
      dentures (RPDs). Common reasons for a failed attachment-retained RPD are fracture
      of the framework, fracture of the roots or teeth, and irretrievable decrease of
      retention. When an RPD framework major connector has been fractured, it should be
      remade. This article describes a technique to remake a fractured mandibular RPD
      using cast round profile attachment analogs without the need for replacement of
      the fixed partial denture.

PMID- 22380648
TI  - Prosthetic requirements for immediate implant loading: a review.
AB  - PURPOSE: The aim of this article is to review the current literature with regard
      to prosthetic considerations and their influence on the outcome of immediately
      loaded implants. MATERIALS AND METHODS: A broad search of the published
      literature was performed using MEDLINE and PubMed to identify pertinent articles.
      RESULTS: One hundred fifty six references were selected. They were mainly
      descriptive, prospective, follow-up studies. They were reviewed and were
      categorized with respect to 6 factors that influence immediate loading: cross
      arch stability and micromovements, interim prostheses, definitive restorations
      inserted immediately, screw- or cement-retained prostheses, occlusion, and number
      and distribution of implants in overdentures and fixed prostheses. CONCLUSION:
      Immediate loading seems to be a relatively safe procedure. From the prosthodontic
      point of view, there are specific guidelines to follow. They are: implants should
      be splinted with a metallic bar and acrylic interim prostheses until full
      osseointegration occurs. To have a successful outcome, screw-retained interim
      prostheses are recommended. CAD/CAM systems can improve the placement of implants
      with minimum risk. Regarding occlusion, there is a disagreement on when and how
      to provide occlusal contacts, but all authors agree on keeping centric contacts
      only. Finally, concerning the number of implants required for an immediate
      overdenture, no conclusive evidence could be found.

PMID- 22380651
TI  - Aliphatic alcohols of illegally produced spirits can act synergistically on
      superoxide-anion production by human granulocytes.
AB  - CONTEXT: Aliphatic alcohols present in illegally produced spirits in a large
      number of low and middle income countries have been implicated in the etiology of
      chronic liver disease and cirrhosis. Previous studies have confirmed that chronic
      alcoholism can lead to increased susceptibility to infectious diseases. Reduced
      superoxide-anion (O(2).(-)) production by granulocytes could provide a mechanism
      by which antimicrobial defense is impaired in alcoholics. In vitro experiments
      have also demonstrated that ethanol can inhibit granulocyte O(2).(-) generation.
      Aliphatic alcohols consumed as contaminants of illicit spirits may also influence
      O(2).(-) production thereby contributing to a decrease in microbicidal activity.
      OBJECTIVE: The aim of this study was to investigate this possibility. It measured
      the O(2).(-) production by human granulocytes following treatment of the cells
      with aliphatic alcohol contaminants found in illicit spirits. MATERIALS AND
      METHODS: Granulocytes were isolated from human buffy coats with centrifugal
      elutriation and then treated with individual aliphatic alcohols and their
      mixture. The O(2).(-) production was stimulated with phorbol-12-13-dibutyrate and
      N-formyl-methionyl-leucyl-phenylalanine (FMLP) and measured by superoxide
      dismutase inhibitable reduction of ferricytochrome c. RESULTS: Aliphatic alcohols
      of illegally produced spirits inhibited the FMLP-induced O(2).(-) production in a
      concentration dependent manner. They suppressed O(2).(-) generation at 2.5-40
      times lower concentrations when combined than when tested individually.
      DISCUSSION AND CONCLUSION: Aliphatic alcohols found in illegally produced spirits
      can inhibit FMLP-induced O(2).(-) production by granulocytes in a concentration
      dependent manner. Due to their synergistic effects, it is possible that, in
      combination with ethanol, they may inhibit O(2).(-) formation in heavy episodic
      drinkers.

PMID- 22380652
TI  - Clients' experiences of housing adaptations: a longitudinal mixed-methods study.
AB  - PURPOSE: To explore clients' experience of the housing adaptations (HAs) over
      time in relation to housing and health. METHOD: A multiple longitudinal case
      study, employing an embedded mixed-method design was used. Four participants were
      included and data from semi-structured interviews were combined with data from
      structured survey assessments. RESULTS: HA made it possible to maintain valuable
      roles and activities, to continue to live in the participants' own homes and to
      take part in the society. The participants strived for autonomy and control, and
      in order to do so they needed different kinds of support, in terms of HA and
      mobility devices as well as support from professionals. HA also challenged the
      participants' routines and habits, as well as their perception about how an
      appealing HA aesthetically. Thus, the decision to apply for a HA was not always
      straightforward. Instead, the participants were constantly engaged in
      negotiations with themselves, concerning benefits and drawbacks of different
      decisions. CONCLUSIONS: HAs involve complex person-environment-activity (P-E-A)
      transactions, and enhance clients' activity and independence in spite of
      functional decline. The knowledge generated is important in order to improve
      individual HA, as well as improving the efficiency and effectiveness of the
      intervention.

PMID- 22380653
TI  - Lead optimization of 17beta-HSD1 inhibitors of the (hydroxyphenyl)naphthol
      sulfonamide type for the treatment of endometriosis.
AB  - The reduction of estrone to estradiol, the most potent estrogen in human, is
      catalyzed by 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1). A
      promising approach for the treatment of estrogen-dependent diseases is the
      reduction of intracellular estradiol formation by inhibition of 17beta-HSD1. For
      the species-specific optimization of the (hydroxyphenyl)naphthols, a
      combinatorial approach was applied and enhanced by a focused synthesis that
      resulted in the aromatic-substituted (hydroxyphenyl)naphthol sulfonamides.
      Rigidification of 12 led to the 4-indolylsulfonamide 30, which is a highly active
      and selective human 17beta-HSD1 inhibitor, as well as a highly potent and
      selective inhibitor of 17beta-HSD1 from Callithrix jacchus. It shows no affinity
      to the estrogen receptors alpha and beta and good intracellular activity (T47D).
      Thus, compound 30 shows good properties for further ADMET studies and might be a
      candidate for the in vivo proof of concept in C. jacchus.

PMID- 22380654
TI  - Coffee cysteine proteinases and related inhibitors with high expression during
      grain maturation and germination.
AB  - BACKGROUND: Cysteine proteinases perform multiple functions in seeds, including
      participation in remodelling polypeptides and recycling amino acids during
      maturation and germination. Currently, few details exist concerning these genes
      and proteins in coffee. Furthermore, there is limited information on the cysteine
      proteinase inhibitors which influence the activities of these proteinases.
      RESULTS: Two cysteine proteinase (CP) and four cysteine proteinase inhibitor
      (CPI) gene sequences have been identified in coffee with significant expression
      during the maturation and germination of coffee grain. Detailed expression
      analysis of the cysteine proteinase genes CcCP1 and CcCP4 in Robusta using
      quantitative RT-PCR showed that these transcripts accumulate primarily during
      grain maturation and germination/post germination. The corresponding proteins
      were expressed in E. coli and purified, but only one, CcCP4, which has a
      KDDL/KDEL C-terminal sequence, was found to be active after a short acid
      treatment. QRT-PCR expression analysis of the four cysteine proteinase inhibitor
      genes in Robusta showed that CcCPI-1 is primarily expressed in developing and
      germinating grain and CcCPI-4 is very highly expressed during the late post
      germination period, as well as in mature, but not immature leaves. Transcripts
      corresponding to CcCPI-2 and CcCPI-3 were detected in most tissues examined at
      relatively similar, but generally low levels. CONCLUSIONS: Several cysteine
      proteinase and cysteine proteinase inhibitor genes with strong, relatively
      specific expression during coffee grain maturation and germination are presented.
      The temporal expression of the CcCP1 gene suggests it is involved in modifying
      proteins during late grain maturation and germination. The expression pattern of
      CcCP4, and its close identity with KDEL containing CP proteins, implies this
      proteinase may play a role in protein and/or cell remodelling during late grain
      germination, and that it is likely to play a strong role in the programmed cell
      death associated with post-germination of the coffee grain. Expression analysis
      of the cysteine proteinase inhibitor genes suggests that CcCPI-1 could primarily
      be involved in modulating the activity of grain CP activity; while CcCPI-4 may
      play roles modulating grain CP activity and in the protection of the young coffee
      seedlings from insects and pathogens. CcCPI-2 and CcCPI-3, having lower and more
      widespread expression, could be more general "house-keeping" CPI genes.

PMID- 22380655
TI  - Prenatal diagnosis of a 22q11 deletion in a second-trimester fetus with
      conotruncal anomaly, absent thymus and meningomyelocele: Kousseff syndrome.
AB  - A 30-year-old nulliparous woman was seen for a detailed ultrasound scan at 20
      weeks of gestation. The scan revealed a male fetus with truncus arteriosus,
      membranous ventricular septal defect, absent thymus and sacral meningomyelocele.
      A 46,XY karyotype with a 22q11 deletion was detected. The parents chose to
      terminate the pregnancy. The pathological autopsy showed normal facial
      structures, minimal ventricular dilatation in the brain and a sacral
      meningomyelocele. Overlapping toes and a left claw-hand were also noted. An
      aplastic thymus with absent parathyroid glands was detected. The cardiac
      examination was consistent with the ultrasound diagnosis. The parental karyotypes
      were both normal. Kousseff syndrome is caused by a chromosome 22q11 deletion. It
      includes sacral meningomyelocele and conotruncal heart defects, unlike DiGeorge
      syndrome. Obstetricians should consider this a not so rare entity when they
      detect conotruncal abnormalities and a meningomyelocele as part of a 22q11.2
      deletion syndrome.

PMID- 22380656
TI  - Biodegradation of kraft lignin by a bacterial strain Comamonas sp. B-9 isolated
      from eroded bamboo slips.
AB  - AIMS: The aim was to obtain evidences for lignin degradation by unicellular
      bacterium Comamonas sp. B-9. METHODS AND RESULTS: Comamonas sp. B-9 was
      inoculated into kraft lignin-mineral salt medium (KL-MSM) at pH 7.0 and 30
      degrees C for 7 days of incubation. The bacterial growth, chemical oxygen demand
      (COD) reduction, secretion of ligninolytic enzymes and productions of low
      molecular-weight compounds revealed that Comamonas sp. B-9 was able to degrade
      kraft lignin (KL). COD in KL-MSM reduced by 32% after 7 days of incubation. The
      maximum activities of manganese peroxidase (MnP) of 2903.2 U l(-1) and laccase
      (Lac) of 1250 U l(-1) were observed at 4th and 6th day, respectively. The low
      molecular-weight compounds such as ethanediol, 3, 5-dimethyl-benzaldehyde and
      phenethyl alcohol were formed in the degradation of KL by Comamonas sp. B-9 based
      on GC-MS analysis. CONCLUSIONS: This study confirmed that Comamonas sp. B-9 could
      utilize KL as a sole carbon source and degrade KL to low-molecular-weight
      compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: Comamonas sp. B-9 may be useful
      in the utilization and bioconversion of lignin and lignin-derived aromatic
      compounds in biotechnological applications. Meanwhile, using Comamonas sp. B-9 in
      treatment of wastewater in pulp and paper industry is a meaningful work.

PMID- 22380657
TI  - Nanopatterned cadmium selenide Langmuir-Blodgett platform for leukemia detection.
AB  - We present results of the studies relating to preparation of Langmuir-Blodgett
      (LB) monolayers of tri-n-octylphosphine oxide-capped cadmium selenide quantum
      dots (QCdSe) onto indium-tin oxide (ITO) coated glass substrate. The monolayer
      behavior has been studied at the air-water interface under various subphase
      conditions. This nanopatterned platform has been explored to fabricate an
      electrochemical DNA biosensor for detection of chronic myelogenous leukemia (CML)
      by covalently immobilizing the thiol-terminated oligonucleotide probe sequence
      via a displacement reaction. The results of electrochemical response studies
      reveal that this biosensor can detect target DNA in the range of 10(-6) to 10(
      14) M within 120 s, has a shelf life of 2 months, and can be used  about 8 times.
      Further, this nucleic acid sensor has been found to distinguish the CML-positive
      and the control negative clinical patient samples.

PMID- 22380658
TI  - Regulating the regulator: MicF RNA controls expression of the global regulator
      Lrp.
AB  - Studies on the regulatory RNA MicF in Enterobacteriaceae reveal a pivotal role in
      gene regulation. Multiple target gene mRNAs were identified and, importantly,
      MicF RNA regulates the expression of the global regulatory gene lrp (Holmqvist et
      al., 2012; Corcoran et al., 2012). Thus MicF RNA is a central factor in a
      regulatory network that regulates bacterial cell physiology.

PMID- 22380659
TI  - Religious objection to cantharidin use in Jain patients.
AB  - We report a case of a Jain family that was upset with the use of cantharidin for
      treatment of molluscum contagiosum for religious reasons.

PMID- 22380660
TI  - Real-effectiveness medicine--pursuing the best effectiveness in the ordinary care
      of patients.
AB  - Clinical know-how and skills as well as up-to-date scientific evidence are
      cornerstones for providing effective treatment for patients. However, in order to
      improve the effectiveness of treatment in ordinary practice, also appropriate
      documentation of care at the health care units and benchmarking based on this
      documentation are needed. This article presents the new concept of real
      effectiveness medicine (REM) which pursues the best effectiveness of patient care
      in the real-world setting. In order to reach the goal, four layers of information
      are utilized: 1) good medical know-how and skills combined with the patient view,
      2) up-to-date scientific evidence, 3) continuous documentation of performance in
      ordinary settings, and 4) benchmarking between providers. The new framework is
      suggested for clinicians, organizations, policy-makers, and researchers.

PMID- 22380661
TI  - Phosphorylated CaMKII post-synaptic binding to NR2B subunits in the anterior
      cingulate cortex mediates visceral pain in visceral hypersensitive rats.
AB  - The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up
      regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis.
      It plays a critical role in modulation of ACC sensitization and visceral pain
      responses. Given the key role of calcium/calmodulin-dependent protein kinase II
      (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize
      that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH
      states. We performed in vivo electroporation of CaMKII siRNA produced inhibition
      of colorectal distension-induced visceromotor response in the VH rats. The NR2B,
      CaMKII and P-CaMKII-Thr286 protein levels were increased in 180%, 220% and 304%
      fold in the post-synaptic density (PSD) fraction in VH rats separately. Western
      blotting following co-immunoprecipitation showed that P-CaMKII-Thr286 bound to
      NR2B in the PSD, which was increased to 267% of control in VH rats.
      Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed
      visceromotor response in VH rats in parallel with decrease of NR2B levels and
      reduction of the NR2B-P-CaMKII-Thr286 protein complex in PSD. In conclusion,
      CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic
      transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit
      at post-synaptic site, modulates visceral pain in viscerally hypersensitive
      state.

PMID- 22380662
TI  - Perioral gustatory sweating: case report.
AB  - OBJECTIVE: Presentation of a case of perioral Frey syndrome. DESIGN: Case report.
      SUBJECT: A 72-year-old woman with hyperhidrosis around the mouth and chin.
      RESULTS: This patient suffered from bilateral perioral gustatory sweating
      following a mandibular osteotomy; such a case has not previously been described.
      Possible pathophysiological hypotheses are discussed in relation to the anatomy
      and innervation of the salivary glands. CONCLUSION: Perioral gustatory sweating
      is a rare complication of osteotomy.

PMID- 22380663
TI  - The relationship of positive and negative expressiveness to the processing of
      emotion information.
AB  - The tendency to express emotions non-verbally is positively related to perception
      of emotions in oneself. This study examined its relationship to perception of
      emotions in others. In 40 healthy adults, EEG theta synchronization was used to
      indicate emotion processing following presentation of happy, angry, and neutral
      faces. Both positive and negative expressiveness were associated with higher
      emotional sensitivity, as shown by cortical responses to facial expressions
      during the early, unconscious processing stage. At the late, conscious processing
      stage, positive expressiveness was associated with higher sensitivity to happy
      faces but lower sensitivity to angry faces. Thus, positive expressiveness
      predisposes people to allocate fewer attentional resources for conscious
      perception of angry faces. In contrast, negative expressiveness was consistently
      associated with higher sensitivity. The effects of positive expressiveness
      occurred in cortical areas that deal with emotions, but the effects of negative
      expressiveness occurred in areas engaged in self-referential processes in the
      context of social relationships.

PMID- 22380664
TI  - Single paracostal approach to thoracic duct and cisterna chyli: experimental
      study and case series.
AB  - OBJECTIVE: To-determine the feasibility of a single paracostal abdominal approach
      for thoracic duct ligation (TDL) and cisterna chyli ablation (CCA) in dogs with
      chylothorax. STUDY DESIGN: Observational study and prospective case series.
      ANIMALS: Normal dogs (n = 5) and dogs with chylothorax (n = 8). METHODS: A single
      paracostal approach with transdiaphragmatic extension for TDL and CCA was
      developed experimentally (n = 5) and used in 8 clinical cases with subtotal
      pericardectomy (SPE) performed in 4 dogs. Surgery time, complications,
      hospitalization time, outcome, and follow-up of clinical cases were recorded.
      RESULTS: Exposure of relevant anatomy was excellent; vital lymphatic staining
      facilitated identification of lymphatic structures. In clinical cases, mean
      surgery time for TDL + CCA was 136 minutes. Mean hospitalization time was 3.1
      days. Seven of 8 cases survived, with 1 dog dying of heart failure shortly after
      discharge. One dog required a second (left) paracostal approach to ligate 2 more
      lymphatic vessels. On follow-up (median, 7 months; range, 2-20 months), there was
      complete resolution of chylothorax in 6 dogs. CONCLUSIONS: A single paracostal
      approach provides excellent exposure of cisterna chyli, caudal thoracic duct, and
      intestinal lymphatics. This approach eliminates the need for repositioning during
      combined TDL + CCA procedures and avoids an intercostal thoracotomy.

PMID- 22380665
TI  - Comparison and description of transdiaphragmatic and abdominal minimally invasive
      cisterna chyli ablation in dogs.
AB  - OBJECTIVE: To develop, describe, and compare transdiaphragmatic (TD) and
      abdominal minimally invasive approaches to cisterna chyli (CC) ablation. STUDY
      DESIGN: Experimental study. ANIMALS: Adult dogs (n = 18; weighing, 19.0 +/- 0.9
      kg). METHODS: With dogs in sternal recumbency, laparoscopic camera and instrument
      portals were established entirely within the craniolateral aspect of the abdomen
      (AB) or in combination with a TD camera portal. A popliteal lymph node was
      injected with methylene blue to provide coloration of the CC in both groups. Once
      the CC was identified, laparoscopic forceps were used to tear and ablate the CC
      tissue. Ablation was confirmed by necropsy examination and observation of blue
      fluid leaking into the peritoneal cavity after injection of the ileocecocolic
      lymph nodes with methylene blue. After censor of the first 2 dogs in each group,
      the AB and TD techniques were compared using procedural time and visual analogue
      scale data of procedure ease, hemorrhage, triangulation efficiency, and adequacy
      of portal placement. RESULTS: Successful CC ablation was achieved in 7 of the TD
      group and 5 of the AB group. Failure was because of an inability to identify the
      CC or tearing of the aorta. Other than a longer procedural time in the TD group,
      there were no statistical differences identified. Complications encountered
      during the procedures led to technical refinements. CONCLUSIONS: Both TD and AB
      minimally invasive approaches can be used to achieve successful CC ablation.

PMID- 22380666
TI  - Occlusion of the thoracic duct using ultrasonically activated shears in six dogs.
AB  - OBJECTIVE: To assess the feasibility of sealing the thoracic duct (TD) in dogs
      using ultrasonically activated shears via thoracoscopy. STUDY DESIGN: In vivo
      experimental study. ANIMALS: Mature dogs (n = 6). METHODS: Dogs were anesthetized
      without pulmonary exclusion and positioned in left lateral recumbency.
      Lymphangiography was performed to identify TD anatomy. Methylene blue was
      injected into the lymphatic catheter to identify the TD and its branches. Under
      thoracoscopic guidance (right dorsal 8-10th intercostal spaces), the TD was
      sealed with an ultrasonic device and lymphangiography was repeated. If the flow
      of contrast continued beyond the occlusion site, additional attempts to seal the
      duct were made. Dogs were euthanatized, the TD was excised and fixed in formalin
      for histopathology. RESULTS: Thoracoscopic identification of the TD was possible
      in 5 dogs. Three dogs required conversion to a thoracoscopic-assisted approach
      and 3 dogs required resealing of the TD closer to the diaphragm. Thoracic duct
      occlusion (TDO) was ultimately achieved in all 6 dogs based on follow-up
      lymphangiography. TDO by tissue coagulation was confirmed by histopathology.
      CONCLUSIONS: Thoracoscopic identification and occlusion of the TD using
      ultrasonically activated shears with bilateral lung ventilation is technically
      feasible in normal dogs and provides a less invasive alternative to open
      thoracotomy procedures.

PMID- 22380667
TI  - Reevaluation of the effect of phenylephrine on resolution of nephrosplenic
      entrapment by the rolling procedure in 87 horses.
AB  - OBJECTIVE: To evaluate the outcome in horses treated with a rolling technique or
      surgically for nephrosplenic entrapment of the large colon (NSE) and to examine
      the benefit of phenylephrine (PE) HCl on the efficacy of nonsurgical (rolling)
      management of NSE. STUDY DESIGN: Case series. ANIMALS: Horses (n = 211) diagnosed
      with NSE by rectal palpation with or without ultrasonography, or at the time of
      exploratory celiotomy or necropsy. METHODS: Medical records (January 1, 2001
      September 1, 2008) were collected from horses diagnosed with NSE at 2 referral
      centers. Records were used to obtain signalment, physical exam findings,
      laboratory results, ultrasonographic findings, the use of PE HCl, the specific
      treatment used, and outcome. Rectal findings indicative of NSE were: (1)
      palpation of large colon within the nephrosplenic space or (2) palpation of
      colonic bands coursing dorsally toward the nephrosplenic space in association
      with ultrasonographic findings suggestive of NSE. RESULTS: Rolling was successful
      in 50 of 87 (58%) horses, 85 horses (98%) survived to discharge. Horses (n = 155)
      that were treated surgically (42 of which had previously undergone the rolling
      procedure) had a 94% short-term survival rate. Premedication with PE resulted in
      no significant difference (P = .91) in resolution of NSE by rolling. CONCLUSIONS:
      Resolution of NSE by rolling was not significantly affected by premedication with
      PE in the population studied.

PMID- 22380668
TI  - Use of a Dacron shape-memory intravascular coil to achieve slow, progressive
      occlusion of the jugular vein in dogs.
AB  - OBJECTIVE: To investigate the ability of shape memory Dacron polymer vascular
      coils to induce the complete, gradual occlusion of the canine jugular vein. STUDY
      DESIGN: Observational pilot study. ANIMALS: Nine purpose-bred dogs. METHODS:
      Eighteen coils were deployed in nine dogs using fluoroscopic-guided percutaneous
      transvenous coil implantation. Individual coil formulations varied around a
      Dacron polymer base. Jugular vein diameter, percent vessel occlusion, and
      thrombus echogenicity were monitored at weekly intervals using ultrasonography.
      Affected jugular veins were harvested at 6 weeks post-implantation and
      histopathological analysis was performed to assess adventitial fibrosis, intimal
      layer thickening, and inflammation. RESULTS: Ten coils migrated from the jugular
      veins to the pulmonary vasculature within 0-2 weeks following implantation. Three
      jugular veins achieved at least 90% occlusion at six weeks. Histopathology of
      these jugular veins revealed marked perivascular thickening and fibrovascular
      proliferation, increased infiltration of macrophages, neutrophils and
      lymphocytes, and abundant fibroplasia. CONCLUSIONS: Complete, gradual occlusion
      of a jugular vein was achieved in three dogs. Significant vessel wall reaction
      and inflammation can induce gradual vessel occlusion when a Dacron coil remains
      implanted within the jugular vein. Dacron polymer coils could be a feasible
      treatment option for the gradual occlusion of congenital portosystemic shunts in
      dogs using minimally invasive, percutaneous transvenous implantation.

PMID- 22380669
TI  - Repair of a bifid nose combined with a cleft of the primary palate in a 1-year
      old dog.
AB  - OBJECTIVE: To report surgical repair of a bifid nose combined with a cleft of the
      primary palate. STUDY DESIGN: Clinical report. ANIMALS: A 1-year-old, male
      castrated Springer spaniel dog. METHODS: With the dog in sternal recumbency, an
      extraoral (dorsal) approach to the nose was performed, and after surgical margins
      were outlined, a Y-shaped skin incision was made to remove redundant tissue and
      expose the bifid nasal cartilages. The cartilages were opposed and sutured
      together and the skin closed in 2 layers. The dog was repositioned in dorsal
      recumbency, and the 2 maxillary first incisor teeth were extracted. After
      tangential incision and undermining of the cleft defect, the mucosa was sutured
      in 1 layer. RESULTS: Healing was uneventful and there was an immediate return to
      normal function. At 2 weeks, 3 and 6 months function was excellent without
      further clinical signs. CONCLUSION: Bifid nose associated with a cleft of the
      primary palate can be surgically corrected.

PMID- 22380670
TI  - Perpendicular pull-out force of locking versus non-locking plates in thin
      cortical bone using a canine mandibular ramus model.
AB  - OBJECTIVE: To compare the holding strength of a conventional plate-screw
      construct with a locking plate-screw construct in the thin cortical bone of the
      canine mandibular ramus. STUDY DESIGN: Mechanical study. ANIMALS: Paired
      cadaveric canine mandibles (n = 10 pairs). METHODS: Perpendicular pull-out
      testing was performed on 2.0-mm limited-contact dynamic compression plate (LC
      DCP)-screw constructs and 2.0-mm string-of-pearls (SOP) plate-screw constructs
      applied to the ramus of the canine mandible. Pull-out force was applied
      perpendicular to the long axis of the plates. Construct stiffness and load at
      failure were determined from load-displacement curves and method of failure was
      determined from high speed digital video recordings. A paired t-test was used to
      compare mean construct stiffness and load at failure between groups. RESULTS: SOP
      plate-screw constructs had a significantly higher mean construct stiffness and
      load at failure than did LC-DCP-screw constructs. LC-DCP constructs failed by
      screw pull-out while bone slicing and fracture were prominent mechanisms of
      failure for SOP constructs. CONCLUSIONS: SOP plate-screw constructs sustained a
      significantly higher perpendicular load at failure than did LC-DCP-screw
      constructs.

PMID- 22380671
TI  - Influence of a resilient, hard-carbon thin film on drilling efficiency and
      thermogenesis.
AB  - OBJECTIVE: To determine changes in drill bit performance attributable to
      application of a triaxially resilient, hard-carbon thin film. STUDY DESIGN: In
      vitro mechanical study. METHODS: Five matched pairs of control bits and bits with
      a carbon nanofilm applied were tested in equine cortical bone and a synthetic
      bone substrate. Thirty sequential holes were drilled with each bit. Drilling time
      was recorded for all holes. Maximum substrate temperature was measured with
      infrared thermography for holes 1, 15, and 30. Drilling time, prolongation of
      drilling time over successive uses, and maximum substrate temperature were
      compared between control and test bits in each substrate. RESULTS: Drilling time
      was significantly reduced with test bits in both substrates. Drilling time over
      successive osteotomies increased more slowly with test bits than with control
      bits. Test bits generated significantly lower substrate temperatures during
      drilling. CONCLUSIONS: Bits with the carbon nanofilm completed osteotomy faster
      and generated less heat than control bits. Test bits also had less degradation of
      drilling performance with repeated use.

PMID- 22380672
TI  - Comparison of the accuracy of radiography and ultrasonography for detection of
      articular lesions in horses.
AB  - OBJECTIVE: To compare the accuracy of ultrasonographic and radiographic
      examination for evaluation of articular lesions in horses. STUDY DESIGN: Cross
      sectional study. ANIMALS: Horses (n = 137) with articular lesions. METHODS:
      Radiographic and ultrasonographic examinations of the affected joint(s) were
      performed before diagnostic or therapeutic arthroscopic surgery. Findings were
      recorded and compared to lesions identified during arthroscopy. RESULTS: In 254
      joints, 432 lesions were identified by arthroscopy. The overall accuracy was
      82.9% for ultrasonography and 62.2% for radiography (P < .0001) with a
      sensitivity of 91.4% for ultrasonography and 66.7% for radiography (P < .0001).
      The difference in specificity was not statistically significant (P = .2628). The
      negative predictive value for ultrasonography was 31.5% and 13.2% for radiography
      (P = .0022), the difference for the positive predictive value was not
      statistically significant (P = .3898). The accuracy for ultrasonography and
      radiography for left versus right joints was equal and corresponded with the
      overall results. CONCLUSIONS: Ultrasonographic evaluation of articular lesions
      was more accurate than radiographic evaluation.

PMID- 22380673
TI  - Use of a suprapatellar pouch portal and laparoscopic cannula for removal of
      debris or loose fragments following arthroscopy of the femoropatellar joint of
      168 horses (245 joints).
AB  - OBJECTIVE: To validate the safety of a suprapatellar pouch (SPP), approach to the
      femoropatellar joint (FPJ), and describe use of a laparoscopic cannula to remove
      debris or loose bodies. STUDY DESIGN: Retrospective case series ANIMALS: Horses
      (n = 168) with osteochondritis dissecans (OCD) of the FPJ. METHODS: Arthroscopy
      was performed on 245 FPJ with OCD. Two subpatellar portals were created, 1 axial
      and 1 abaxial to the lateral patellar ligament. Additionally, a SPP egress portal
      for lavage, was created 2 cm proximal to the most palpable dorsolateral eminence
      of the patellar base. A 10-mm laparoscopic cannula and trocar unit was used in
      all SPP portals. The SPP portal was closed in 2 layers in the first 121 horses
      and the skin only in the remaining 47 horses. Medical records were reviewed for
      complications and surgical time and owner satisfaction with cosmesis obtained.
      RESULTS: No complications were recorded for the SPP portal regardless of closure
      technique. All owners were satisfied with the cosmetic outcome of the procedure
      once the hair had grown back and felt the additional incision did not negatively
      impact horses presented for sale at public auction. Mean surgery time was 27.7
      min/joint. CONCLUSION: No complications were recorded using a SPP portal and
      laparoscopic cannula, and owner satisfaction was high.

PMID- 22380674
TI  - Effect of experimentally induced synovitis on amikacin concentrations after
      intravenous regional limb perfusion.
AB  - OBJECTIVES: To determine the effects of experimentally induced synovitis of the
      radiocarpal joint on the intra-articular pharmacokinetics and pharmacodynamics of
      amikacin after intravenous regional limb perfusion (IVRLP). STUDY DESIGN:
      Randomized crossover experimental design. ANIMALS: Adult horses (n = 8). METHODS:
      Horses were randomly assigned into 2 trials: synovitis and no-synovitis.
      Radiocarpal joint synovitis was induced with lipopolysaccharide 6 hours before
      IVRLP. IVRLP (5-mg/kg amikacin qs 60 mL) was performed with a pneumatic
      tourniquet under general anesthesia. Synovial fluid was obtained before and 0.5,
      1, 3, 5, 12, 24, 48 hours after IVRLP. Amikacin concentrations at each time point
      and pharmacokinetic values were compared between synovitis and no-synovitis
      trials with Student's t-test. RESULTS: Amikacin synovial fluid concentrations
      indicated suspected tourniquet failure on 3 occasions (2 synovitis, 1 no
      synovitis) on 3 different horses. Data from both trials in these 3 horses were
      excluded from further analysis. Observed time to maximal concentration (T(max);
      mean +/- SD = 54 +/- 13.42 min) was reached earlier in synovitis joints (5/5, 30
      min) than in no-synovitis joints (1/5, 30 min and 4/5, 1 h; P = .0476) (P =
      .0161). Mean observed maximal concentration (C(max)) was higher in synovitis
      joints (144.48 +/- 43.17 MUg/mL) than in no-synovitis joints (60.02 +/- 28.81
      MUg/mL; P = .0301). The recommended C(max): minimum inhibitory concentration
      ratio of 8 was achieved in 3/5 of the successfully perfused joints with induced
      synovitis, but this ratio was not achieved in any of the clinically normal
      joints. CONCLUSION: Synovitis of the radiocarpal joint resulted in an earlier
      observed T(max) and higher observed C(max) of intra-articular amikacin after
      IVRLP compared with normal joints.

PMID- 22380675
TI  - A preliminary study on the effect of manuka honey on second-intention healing of
      contaminated wounds on the distal aspect of the forelimbs of horses.
AB  - OBJECTIVE: To determine the effect of manuka honey on second-intention healing of
      contaminated, full-thickness skin wounds in horses. STUDY DESIGN: Experimental.
      ANIMALS: Adult Standardbred horses (n = 8). METHODS: One wound was created on the
      dorsomedial aspect of the third metacarpus in both forelimbs, contaminated with
      feces, and bandaged for 24 hours. Bandages were removed and wounds rinsed with
      isotonic saline solution. Wounds on 1 limb had manuka honey applied daily (n = 8)
      whereas wounds on the contralateral limb received no treatment (n = 8). Bandages
      were replaced and changed daily for 12 days, after which treatment stopped,
      bandages were removed, leaving wounds open to heal. Wound area was measured 24
      hours after wound creation (day 1), then weekly for 8 weeks. Overall time for
      healing was recorded. Wound area and rate of healing of treated and control
      wounds were compared statistically. RESULTS: Treatment with manuka honey
      decreased wound retraction and treated wounds remained significantly smaller than
      control wounds until day 42; however, there was no difference in overall healing
      time between treatment and control wounds. CONCLUSIONS: Treatment with manuka
      honey reduced wound area by reducing retraction but did not affect overall
      healing time of full-thickness distal limb wounds using this wound-healing model.

PMID- 22380676
TI  - Mandibular fracture in single-humped camels.
AB  - OBJECTIVE: To report the causes and classification of mandibular fractures in
      dromedary camels and outcome after treatment. ANIMALS: Single-humped camels (n =
      116) with mandibular fracture. METHODS: At admission, cause, site,
      classification, and radiography of mandibular fractures were recorded. Factors
      affecting fracture healing were analyzed. RESULTS: Biting was the main cause of
      mandibular fractures in camels, which occurred more commonly in older males (P =
      .001) than in females. Open fractures were more common than closed ones (92.2%
      versus 7.8%, P = .0001) and single fractures were more frequent (82%) than
      multiple and comminuted fractures (18%; P = .001). Fractures were treated by
      interdental wiring (91.2%) or U-shaped aluminum bar (8.8%) and healing occurred
      in most (83.2%) fractures. CONCLUSIONS: In dromedary camels, mandibular fracture
      is most commonly caused by bites and can be successfully repaired by interdental
      wiring or a U-bar technique with good outcome.

PMID- 22380677
TI  - The Thermococcus kodakaraensis Tko CDC21-1 intein activates its N-terminal splice
      junction in the absence of a conserved histidine by a compensatory mechanism.
AB  - Inteins and other self-catalytic enzymes, such as glycosylasparaginases and
      hedgehog precursors, initiate autocleavage by converting a peptide bond to a
      (thio)ester bond when Ser, Thr, or Cys undergoes an N-[S/O] acyl migration
      assisted by residues within the precursor. Previous studies have shown that a His
      at position 10 in intein Block B is essential for this initial acyl migration and
      N-terminal splice junction cleavage. This His is present in all inteins
      identified to date except the Thermococcus kodakaraensis Tko CDC21-1 intein
      orthologs and the inactive Arthrobacter species FB24 Arth_1007 intein. This study
      demonstrates that the Tko CDC21-1 intein is fully active and has replaced the
      lost catalytic function normally provided by the Block B His using a compensatory
      mechanism involving a conserved ortholog-specific basic residue (Lys(58)) present
      outside the standard intein conserved motifs. We propose that Lys(58) catalyzes
      the initial N-S acyl migration by stabilizing the thiazolidine-tetrahedral
      intermediate, allowing it to be resolved by water-mediated hydrolysis rather than
      by protonating the leaving group as His is theorized to do in many other inteins.
      Autoprocessing enzymes may have more flexibility in evolving catalytic variations
      because high reaction rates are not required when performing single-turnover
      reactions on "substrates" that are covalently attached to the enzyme.
      Consequently, inteins have more flexibility to sample catalytic mechanisms,
      providing insight into various strategies that enzymes use to accomplish
      catalysis.

PMID- 22380678
TI  - Role of oxidative stress in preeclampsia and intrauterine growth restriction.
AB  - AIM: The aim of the present study was to evaluate the role of oxidative stress
      and DNA damage in preeclampsia and intrauterine growth restriction (IUGR).
      MATERIAL AND METHODS: Twenty-four patients with preeclampsia, 20 patients with
      IUGR fetus and 37 healthy pregnant women were enrolled in the study. The total
      oxidant status (TOS) and antioxidant status (TAS) of plasma were measured using a
      novel automated colorimetric measurement method. Sister chromatid exchange (SCE)
      and micronuclei analysis were performed on peripheral blood lymphocytes of cases
      and controls. RESULTS: Women whose pregnancies were complicated with preeclampsia
      and IUGR had elevated levels of TOS and TAS when compared with healthy pregnant
      women (median TOS values: 9.73, 10.6 and 8.06, P = 0.001; median TAS values: 1.
      77, 1.54 and 1.44, P < 0.001, respectively). The frequencies of SCE were only
      found to be increased in women with IUGR fetus compared with healthy pregnant
      women (8.81 vs 7.5, respectively, P = 0.02). Multivariable linear regression
      analysis for both TOS and TAS showed a significant relation between these
      variables and uric acid. CONCLUSION: Increased oxidative stress and antioxidative
      defense mechanisms may contribute to disease processes both in preeclampsia and
      IUGR.

PMID- 22380679
TI  - Arterial dP/dtmax accurately reflects left ventricular contractility during shock
      when adequate vascular filling is achieved.
AB  - BACKGROUND: Peak first derivative of femoral artery pressure (arterial dP/dtmax)
      derived from fluid-filled catheter remains questionable to assess left
      ventricular (LV) contractility during shock. The aim of this study was to test if
      arterial dP/dtmax is reliable for assessing LV contractility during various
      hemodynamic conditions such as endotoxin-induced shock and catecholamine
      infusion. METHODS: Ventricular pressure-volume data obtained with a conductance
      catheter and invasive arterial pressure obtained with a fluid-filled catheter
      were continuously recorded in 6 anaesthetized and mechanically ventilated pigs.
      After a stabilization period, endotoxin was infused to induce shock.
      Catecholamines were transiently administrated during shock. Arterial dP/dtmax was
      compared to end-systolic elastance (Ees), the gold standard method for assessing
      LV contractility. RESULTS: Endotoxin-induced shock and catecholamine infusion
      lead to significant variations in LV contractility. Overall, significant
      correlation (r=0.51; p<0.001) but low agreement between the two methods were
      observed. However, a far better correlation with a good agreement were observed
      when positive-pressure ventilation induced an arterial pulse pressure variation
      (PPV)<=11% (r=0.77; p<0.001). CONCLUSION: While arterial dP/dtmax and Ees were
      significantly correlated during various hemodynamic conditions, arterial dP/dtmax
      was more accurate for assessing LV contractility when adequate vascular filling,
      defined as PPV<=11%, was achieved.

PMID- 22380680
TI  - Inhibition of homologous recombination in human cells by targeting RAD51
      recombinase.
AB  - The homologous recombination (HR) pathway plays a crucial role in the repair of
      DNA double-strand breaks (DSBs) and interstrand cross-links (ICLs). RAD51, a key
      protein of HR, possesses a unique activity: DNA strand exchange between
      homologous DNA sequences. Recently, using a high-throughput screening (HTS), we
      identified compound 1 (B02), which specifically inhibits the DNA strand exchange
      activity of human RAD51. Here, we analyzed the mechanism of inhibition and found
      that 1 disrupts RAD51 binding to DNA. We then examined the effect of 1 on HR and
      DNA repair in the cell. The results show that 1 inhibits HR and increases cell
      sensitivity to DNA damage. We propose to use 1 for analysis of cellular functions
      of RAD51. Because DSB- and ICL-inducing agents are commonly used in anticancer
      therapy, specific inhibitors of RAD51 may also help to increase killing of cancer
      cells.

PMID- 22380682
TI  - Dolutegravir  for the treatment of HIV.
AB  - INTRODUCTION: Development of new antiretroviral drugs which are highly potent,
      tolerable over the long term and with a high genetic barrier to resistance is
      essential for the treatment of a chronic viral disease that requires life-long
      therapy with near-perfect medication adherence. Integrase inhibitors (INI) are a
      new class of antiretroviral drugs that block the action of HIV integrase, which
      catalyses several key steps in the virus life cycle which are essential for
      insertion of the viral genome into the DNA of host cell. AREAS COVERED:
      Dolutegravir (DTG), a second-generation INI currently in the late stage of
      clinical development, is an effective orally available drug with a long half-life
      that does not need to be pharmacologically enhanced, is effective as a once daily
      drug in the absence of INI resistance mutations and twice daily in presence of
      INI resistance mutations. EXPERT OPINION: DTG, as other drugs in the INI class,
      appears safe and well tolerated. Results from ongoing large Phase III studies
      will bring more generalizable and robust information on the long-term effects of
      DTG.

PMID- 22380681
TI  - Imbalance of heterologous protein folding and disulfide bond formation rates
      yields runaway oxidative stress.
AB  - BACKGROUND: The protein secretory pathway must process a wide assortment of
      native proteins for eukaryotic cells to function. As well, recombinant protein
      secretion is used extensively to produce many biologics and industrial enzymes.
      Therefore, secretory pathway dysfunction can be highly detrimental to the cell
      and can drastically inhibit product titers in biochemical production. Because the
      secretory pathway is a highly-integrated, multi-organelle system, dysfunction can
      happen at many levels and dissecting the root cause can be challenging. In this
      study, we apply a systems biology approach to analyze secretory pathway
      dysfunctions resulting from heterologous production of a small protein (insulin
      precursor) or a larger protein (alpha-amylase). RESULTS: HAC1-dependent and
      independent dysfunctions and cellular responses were apparent across multiple
      datasets. In particular, processes involving (a) degradation of protein/recycling
      amino acids, (b) overall transcription/translation repression, and (c) oxidative
      stress were broadly associated with secretory stress. CONCLUSIONS: Apparent
      runaway oxidative stress due to radical production observed here and elsewhere
      can be explained by a futile cycle of disulfide formation and breaking that
      consumes reduced glutathione and produces reactive oxygen species. The futile
      cycle is dominating when protein folding rates are low relative to disulfide bond
      formation rates. While not strictly conclusive with the present data, this
      insight does provide a molecular interpretation to an, until now, largely
      empirical understanding of optimizing heterologous protein secretion. This
      molecular insight has direct implications on engineering a broad range of
      recombinant proteins for secretion and provides potential hypotheses for the root
      causes of several secretory-associated diseases.

PMID- 22380684
TI  - Parent-adolescent dyads: association of parental autonomy support and parent
      adolescent shared diabetes care responsibility.
AB  - PURPOSE: Parent-adolescent shared responsibility for diabetes care is advocated
      by experts to achieve beneficial diabetes and psychosocial outcomes for
      adolescents with type 1 diabetes. Parental autonomy support may be a way to
      facilitate this sharing. In this dyadic study, we examined parental diabetes
      specific autonomy support experienced by adolescents with type 1 diabetes and
      their parents (n = 89 dyads), and its association with their experience of shared
      diabetes care responsibility. METHODS: Path analysis was used to test an Actor
      Partner Interdependence Model for parental autonomy support effects on shared
      responsibility. This was a secondary analysis of data from 89 parent-early/mid
      adolescent dyads. RESULTS: Actor effects were identified. Parents' and
      adolescents' perceptions of parental autonomy support were associated with their
      respective reports of shared diabetes care responsibility. One partner effect was
      identified. Adolescents' reports of parental autonomy support were associated
      with parents' reports of shared responsibility. Parents and adolescents held
      similar views of autonomy support but discrepant views of shared responsibility.
      Older adolescents perceived less parental autonomy support. CONCLUSION:
      Increasing parental autonomy support may facilitate parent-adolescent sharing of
      diabetes care responsibility. Adolescent and parent perceptions influence each
      other and need to be considered when working with them to strengthen parental
      autonomy support.

PMID- 22380685
TI  - Smoking habit, serum cotinine and placental abruption.

PMID- 22380686
TI  - Liquid chromatography-mass spectrometry-based metabolomic analysis of livers from
      aged rats.
AB  - We used UPLC-Q-TOF MS to analyze hepatic metabolites of rats aged 6, 12, 18, and
      24 months; the MS data were processed by partial least-squares discriminant
      analysis (PLS-DA) to investigate the discrimination among sample groups. Rats
      were significantly separated with increasing age, except those aged between 6 and
      12 months. We identified only 25 of 120 metabolites contributing to the
      separation: lipid metabolites (glycerol-3-phosphate, linolenic acid,
      lysophosphatidylcholines [lysoPCs]), energy metabolism intermediates (betaine,
      carnitine, acylcarnitines, creatine, pantothenic acid), nucleic acid metabolites
      (inosine, xanthosine, uracil, hypoxanthine, xanthine), and tyrosine. Aging
      accumulated energy metabolism intermediates, hypoxanthine, xanthine, and 2 major
      lysoPCs (C18:0 and C22:6). The NAD level and NAD/NADH ratio decreased with age.
      It was indicated that aging might decrease energy production through beta
      oxidation because of a decrease in NAD despite the accumulation of lipid energy
      metabolism intermediates. In addition to energy dysregulation, hypoxanthine and
      xanthine, which are elevated with age, might accumulate reactive oxygen species
      in the liver. These results strongly support two aging theories: those of energy
      dysregulation and free radicals. Additionally, we propose a metabolic pathway
      related to aging based on these hepatic metabolites. These metabolites and the
      proposed aging pathway could be used to understand aging and related diseases
      better, and increase the predictability of aging risk.

PMID- 22380687
TI  - The role of endogenous and exogenous enzymes in chronic wounds: a focus on the
      implications of aberrant levels of both host and bacterial proteases in wound
      healing.
AB  - Cutaneous wound healing is orchestrated by a number of physiological pathways
      that ultimately lead to reformation of skin integrity and the production of
      functional scar tissue. The remodeling of a wound is significantly affected by
      matrix metalloproteinases (MMPs), which act to control the degradation of the
      extracellular matrix (ECM). Regulation of MMPs is imperative for wound healing as
      excessive levels of MMPs can lead to disproportionate destruction of the wound
      ECM compared to ECM deposition. In addition to human MMPs, bacterial proteases
      have been found to be influential in tissue breakdown and, as such, have a role
      to play in the healing of infected wounds. For example, the zinc
      metalloproteinase, elastase, produced by Pseudomonas aeruginosa, induces
      degradation of fibroblast proteins and proteoglycans in chronic wounds and has
      also been shown to degrade host immune cell mediators. Microbial extracellular
      enzymes have also been shown to degrade human wound fluid and inhibit fibroblast
      cell growth. It is now being acknowledged that host and bacterial MMPs may act
      synergistically to cause tissue breakdown within the wound bed. Several studies
      have suggested that bacterial-derived secreted proteases may act to up-regulate
      the levels of MMPs produced by the host cells. Together, these findings indicate
      that bacterial phenotype in terms of protease producing potential of bacteria
      should be taken into consideration during diagnostic and clinical intervention of
      infected wound management. Furthermore, both host MMPs and those derived from
      infecting bacteria need to be targeted in order to increase the healing capacity
      of the injured tissue. The aim of this review is to investigate the evidence
      suggestive of a relationship between unregulated levels of both host and
      bacterial proteases and delayed wound healing.

PMID- 22380688
TI  - Role of cytokines in lavage or drainage fluid after hemithyroidectomy in wound
      healing: involvement of histamine in the acceleration and delay of wound healing.
AB  - Wound healing is a sophisticated biologic process. In the case of
      hemithyroidectomy, the operation time is relatively short with small tissue
      damage and without skin excision, and bacterial contamination before, during, and
      after the operation is uncommon. Here, we explored which cytokine(s) affected the
      rates of healing of skin wounds after hemithyroidectomy of 29 patients. We
      assessed the amounts of cytokines (e.g., interleukin-6, platelet-derived growth
      factor, basic fibroblast growth factor, vascular endothelial growth factor, and
      tumor necrosis factor-alpha) in either the preoperative or postoperative lavage
      fluids, or in the drainage fluids on postoperative days (PODs) 1-8. All of these
      cytokines showed a similar pattern; after reaching a peak on POD1, the production
      fell sharply on POD2-8, revealing that wound healing commenced on POD1. The rates
      of wound healing were inversely related to the levels of histamine in six
      patients (i.e., those with the three largest and those with the three smallest
      total volumes of drainage fluid on POD1): high (or low) levels of histamine in
      the postoperative lavage fluids with low (or high) levels in the drainage fluids
      on POD1 caused earlier (or the delay of) wound healing, suggesting involvement of
      histamine in the acceleration and delay of wound healing.

PMID- 22380689
TI  - Impaired cutaneous wound healing in transforming growth factor-beta inducible
      early gene1 knockout mice.
AB  - Transforming growth factor-beta inducible early gene (TIEG) is induced by
      transforming growth factor-beta (TGF-beta) and acts as the primary response gene
      in the TGF-beta/Smad pathway. TGF-beta is a multifunctional growth factor that
      affects dermal wound healing; however, the mechanism of how TGF-beta affects
      wound healing is still not well understood because of the complexity of its
      function and signaling pathways. We hypothesize that TIEG may play a role in
      dermal wound healing, with involvement in wound closure, contraction, and
      reepithelialization. In this study, we have shown that TIEG1 knockout (TIEG1-/-)
      mice have a delay in wound closure related to an impairment in wound contraction,
      granulation tissue formation, collagen synthesis, and reepithelialization. We
      also found that Smad7 was increased in the wounds and appeared to play a role in
      this wound healing model in TIEG1-/- mice.

PMID- 22380690
TI  - Diabetes-impaired wound healing and altered macrophage activation: a possible
      pathophysiologic correlation.
AB  - Macrophages play a critical role in wound healing and can be activated to two
      distinctive phenotypes in vitro: classical macrophage activation (caM) and
      alternative macrophage activation (aaM). This study investigated whether the
      impaired cutaneous repair observed in streptozotocin-induced diabetic rats was
      associated with altered macrophage activation. Our results show that macrophage
      activation phenotypes could be observed in wound healing through double
      immunostaining. The caM macrophages appeared in the initial stage of wound
      healing, followed by aaM macrophages, which predominated in normal wounds.
      However, through examining markers associated with activation by immunoblotting
      and real-time polymerase chain reaction (PCR), diabetic wounds demonstrated
      insufficient caM in the early stage but excessive aaM in the later proliferative
      phase. Moreover, the macrophage activation markers were correlated with the
      instructive T helper cell type 1 (Th1)/Th2 cytokines in both groups. It was
      indicated that changed macrophage activation might contribute to impaired healing
      in diabetes wounds, and that strategies for reverting this abnormal activation
      could be useful for enhancing the wound healing process.

PMID- 22380691
TI  - Green light emitting diodes accelerate wound healing: characterization of the
      effect and its molecular basis in vitro and in vivo.
AB  - Because light-emitting diodes (LEDs) are low-coherent, quasimonochromatic, and
      nonthermal, they are an alternative for low level laser therapy, and have
      photobiostimulative effects on tissue repair. However, the molecular mechanism(s)
      are unclear, and potential effects of blue and/or green LEDs on wound healing are
      still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm),
      and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the
      skin of ob/ob mice were significantly decreased on day 7 following exposure to
      green LEDs, and complete reepithelialization was accelerated by red and green
      LEDs compared with the control mice. To better understand the molecular
      mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts
      in vitro by measuring mRNA and protein levels of cytokines secreted by
      fibroblasts during the process of wound healing and on the migration of HaCat
      keratinocytes. The results suggest that some cytokines are significantly
      increased by exposure to LEDs, especially leptin, IL-8, and VEGF, but only by
      green LEDs. The migration of HaCat keratinocytes was significantly promoted by
      red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound
      healing by inducing migratory and proliferative mediators, which suggests that
      not only red LEDs but also green LEDs can be a new powerful therapeutic strategy
      for wound healing.

PMID- 22380693
TI  - Stimulation of GluN receptors decreases the surface density of GluN1/GluN2B
      subunits in cultured neocortical interneurons.
AB  - Changes in the density of NMDA (GluN) receptors in the neuronal membrane are
      critical for plasticity, whereas malfunction of precisely regulated GluN receptor
      activity may be involved in neurotoxicity. In cultured rat neocortical
      interneurons, we have studied the regulation of the surface density of GluN1,
      GluN2A and GluN2B subunits. Application of 5 MUMol NMDA for 24 h followed by a
      washout period of 24 h decreased the response of GluN receptors for at least 2
      days. The reduction was caused by a decrease in the surface density of
      GluN1/GluN2B subunits, whereas GluN2A subunits remained unaffected. Our data
      indicate that long but reversible low level activation of GluN receptors can
      cause long-term changes in their subunit composition in cultured interneurons.

PMID- 22380694
TI  - A contemporary viewpoint on 'aspirin resistance'.
AB  - Aspirin is an irreversible inhibitor of platelet prostaglandin synthase activity,
      and is the most widely prescribed drug for the secondary prevention of
      cardiovascular disease. In recent years, clinical and laboratory evidence has
      shown significant individual variability in the response to aspirin and its link
      to clinical outcome. The term 'aspirin resistance' has been introduced to
      describe situations when clinical or ex-vivo effects of aspirin are less than
      expected. The accumulating evidence of increased risk of major adverse clinical
      events (MACE) associated with 'aspirin resistance' in the settings of acute
      coronary syndrome (ACS), stroke, and peripheral arterial disease has stimulated
      the search for ways of overcoming aspirin resistance. Existence of the link
      between high on-treatment platelet reactivity and atherothrombotic events
      suggests the common mechanisms for atherosclerosis progression and thrombotic
      complications with the platelets, being a key cellular interface between
      coagulation and inflammation. This review article provides a contemporary view on
      'aspirin resistance' and discusses its definition, clinical importance, and
      possible mechanisms in light of recent data on the role of platelets in
      atherothrombosis.

PMID- 22380695
TI  - Thrombospondin-4, tumour necrosis factor-like weak inducer of apoptosis (TWEAK)
      and its receptor Fn14: novel extracellular matrix modulating factors in cardiac
      remodelling.
AB  - Cardiac remodelling is defined as changes in the size, shape, and function of the
      heart, which are most commonly caused by hypertension-induced left ventricular
      hypertrophy and myocardial infarction. Both neurohumoral and inflammatory factors
      have critical roles in the regulation of cardiac remodelling. A characteristic
      feature of cardiac remodelling is modification of the extracellular matrix (ECM),
      often manifested by fibrosis, a process that has vital consequences for the
      structure and function of the myocardium. In addition to established modulators
      of the ECM, the matricellular protein thrombospondin-4 (TSP-4) as well as the
      tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor
      Fn14 has been recently shown to modulate cardiac ECM. TSP-4 null mice develop
      pronounced cardiac hypertrophy and fibrosis with defects in collagen maturation
      in response to pressure overload. TWEAK and Fn14 belong to the tumour necrosis
      factor superfamily of proinflammatory cytokines. Recently it was shown that
      elevated levels of circulating TWEAK via Fn14 critically affect the cardiac ECM,
      characterized by increasing fibrosis and cardiomyocyte hypertrophy in mice. Here
      we review the literature concerning the role of matricellular proteins and
      inflammation in cardiac ECM remodelling, with a special focus on TSP-4, TWEAK,
      and its receptor Fn14.

PMID- 22380697
TI  - Lacosamide for the treatment of epilepsy.
AB  - Lacosamide is a third-generation antiepilepsy drug approved for adjunctive
      treatment of partial-onset seizures in adults. The pharmacology of lacosamide
      includes linear kinetics, complete bioavailability, and no major drug
      interactions. Lacosamide produces slow inactivation of neuronal sodium channels,
      which differentiates it from other sodium channel modulators, such as
      carbamazepine and phenytoin. The drug was effective with no major safety problems
      detected in three large placebo-controlled pivotal trials and has been released
      in Europe and the US at 200-400 mg/day, divided b.i.d.; an intravenous
      formulation is approved for temporary conversion from oral therapy. This article
      reviews the clinical development, pharmacology, and uses of lacosamide for
      treating partial-onset seizures in adults.

PMID- 22380698
TI  - Treatment of early-onset Gorham syndrome with 8-year follow-up.
AB  - A case of Gorham disease with several years of follow-up is reported. At birth he
      had a mass in the thigh which was had pathology demonstrating a lymphangioma. By
      age 3 years, he had lymphedema of the ipsilateral foot and discrepant leg
      lengths. Radiography revealed heterogenous dystrophy of the bones and osteolysis
      of the hallux. At age 6, a spontaneous fracture of the right tibia was treated
      with surgery. Histopathology of a bone sample demonstrated bone remodelling,
      fibrous tissue, and large vascular lacunas within bone tissue, bordered by cells
      expressing the lymphaticmarker D2-40. At 8 years old, lymphedema of the right
      inferior leg had increased, leg lengths still differed, but other clinical signs
      were absent.

PMID- 22380699
TI  - Use of biocides for the control of fungal outbreaks in subterranean environments:
      the case of the Lascaux Cave in France.
AB  - The Lascaux Cave in France suffered an outbreak of the fungus Fusarium solani in
      2001. Biocides were applied for three years to control this outbreak. Four months
      after the initial biocide application, a new outbreak appeared in the form of
      black stains that progressively invaded the cave. The black stains on the ceiling
      and passage banks were so evident by 2007 that they became one of the cave's
      major problems. Therefore, biocides were used again in 2008. The present study
      investigated the fungal communities associated with the black stains and the
      effectiveness of the biocides applied, by using cloning, denaturing gradient gel
      electrophoresis, and culture-dependent methods. A novel species, Ochroconis
      lascauxensis, was the most abundant fungus in samples collected between 2007 and
      2008, and the biocides applied were not effective in eliminating this fungus; on
      the contrary, they appeared to increase the fungal diversity. The fungal
      communities represented in the samples collected in 2010 were quite different
      from those collected in 2008 and 2009: the major OTUs corresponded to black
      yeasts belonging to the Herpotrichiellaceae family. The origin and evolution of
      these microorganisms are probably linked to the intensive biocide treatments and
      to the anthropogenic changes introduced by cave management.

PMID- 22380700
TI  - Right intercostal insertion of a Veress needle for laparoscopy in dogs.
AB  - OBJECTIVE: To evaluate right intercostal Veress needle (VN) insertion for
      laparoscopy in dogs. STUDY DESIGN: Longitudinal cohort study. ANIMALS: Female
      dogs (n = 56). METHODS: The VN was inserted in the last palpable right
      intercostal space, either 1/3 (Group T; 28 dogs) or mid distance (Group H; 28
      dogs) from the xiphoid cartilage to the most caudal extent of the costal arch.
      Problems encountered during VN insertion and injuries were recorded, graded, and
      compared between groups, and also between the first and last 20 insertions.
      RESULTS: Pneumoperitoneum was successfully achieved by VN insertion in 49 (88%)
      dogs after a single (45 dogs) or 2nd attempt (4 dogs). Frequency of complications
      was as follows: 20 grade 1 (subcutaneous emphysema, omentum, or falciform
      injuries); 6 grade 2 (liver or spleen injury), and 1 grade 3 complication
      (pneumothorax occurred). No significant difference was found between the 2 groups
      or between the first and last 20 dogs. CONCLUSIONS: Right intercostal VN
      insertion facilitates pneumoperitoneum in dogs with few consequential
      complications. No significant difference was found between entry sites; however,
      the mid distance insertion site in the last palpable intercostal space with dog
      positioned in dorsal recumbency is likely to result in less complications.

PMID- 22380701
TI  - Behavioural determinants of salt consumption among hypertensive individuals.
AB  - BACKGROUND: High salt consumption among populations remains a challenge for
      health professionals dealing with prevention and control of hypertension. The
      present study aimed to identify the psychosocial predictors of salt consumption
      among hypertensive individuals, based on an extended version of the Theory of
      Planned Behaviour (TPB). Three salt consumption behaviours were studied:
      Behaviour 1- using <4 g of salt per day during cooking; Behaviour 2- avoiding
      adding salt/table salt use to the prepared foods; and Behaviour 3- avoiding the
      consumption of foods with high salt content. METHODS: At baseline (n = 108), TPB
      and additional variables (self-efficacy, habit, past behaviour, hedonic
      determinant, self-perceived diet quality) were measured. At 2-month follow-up (n
      = 95), the three behaviours were assessed. Behaviour and intention were
      sequentially regressed on the study variables, using polytomous logistic
      regression and hierarchical linear regression with rank transformation,
      respectively. RESULTS: Behaviour 1 was predicted by intention [odds ratio (OR) =
      6.23; 95% confidence interval (CI) = 1.81-21.52], whereas self-efficacy and habit
      predicted intention. Behaviour 2 exhibited high score mean and low variation and
      was predicted by self-perceived diet quality (OR = 2.56; 95% CI = 1.03-6.36).
      Behaviour 3 was predicted by the hedonic determinant (OR = 1.42; 95% CI = 1.01
      1.98). CONCLUSIONS: The results indicate that salt-related behaviours are
      explained by a variety of determinants. Among these determinants, special
      consideration should be given to motivational and hedonic aspects.

PMID- 22380696
TI  - Vascular aging: chronic oxidative stress and impairment of redox signaling
      consequences for vascular homeostasis and disease.
AB  - Characteristic morphological and molecular alterations such as vessel wall
      thickening and reduction of nitric oxide occur in the aging vasculature leading
      to the gradual loss of vascular homeostasis. Consequently, the risk of developing
      acute and chronic cardiovascular diseases increases with age. Current research of
      the underlying molecular mechanisms of endothelial function demonstrates a
      duality of reactive oxygen and nitrogen species in contributing to vascular
      homeostasis or leading to detrimental effects when formed in excess. Furthermore,
      changes in function and redox status of vascular smooth muscle cells contribute
      to age-related vascular remodeling. The age-dependent increase in free radical
      formation causes deterioration of the nitric oxide signaling cascade, alters and
      activates prostaglandin metabolism, and promotes novel oxidative
      posttranslational protein modifications that interfere with vascular and cell
      signaling pathways. As a result, vascular dysfunction manifests. Compensatory
      mechanisms are initially activated to cope with age-induced oxidative stress, but
      become futile, which results in irreversible oxidative modifications of
      biological macromolecules. These findings support the 'free radical theory of
      aging' but also show that reactive oxygen and nitrogen species are essential
      signaling molecules, regulating vascular homeostasis.

PMID- 22380703
TI  - Effect of lipopolysaccharide on the production of prostaglandin E2 and inhibition
      of uterine contractions by nitric oxide in pregnant inducible nitric oxide
      synthase knockout mice.
AB  - AIM: The aim of the present study was to evaluate the effect of
      lipopolysaccharide (LPS) on the production of prostaglandin E2 (PGE2) and
      inhibition by nitric oxide (NO) of spontaneous contractions of uterine rings from
      pregnant inducible isoform of nitric oxide synthase knockout (iNOS KO) mice.
      MATERIAL AND METHODS: iNOS KO and wild-type mice were sacrificed 6 h after
      intraperitoneal (i.p.) administration of LPS on day 14 of gestation. Uterine
      rings were equilibrated in Krebs-Henseleit solution for isometric tension
      recording. In part of the uterine rings, placental tissues were left attached.
      The bathing solution was analyzed for PGE2 by radioimmunoassay. Changes in
      spontaneous contractions in response to cumulative concentrations of L-arginine,
      diethylamine/nitric oxide (DEA/NO), and 8-bromo-cyclic guanosine monophosphate (8
      br-cGMP) were determined. RESULTS: Treatment with LPS increased PGE2 production
      by uterine rings from wild-type and iNOS-KO mice. DEA/NO and 8-br-cGMP inhibited
      spontaneous contractions in uterine rings in the absence or presence of placenta,
      in both LPS-treated and LPS-untreated animals. LPS treatment attenuated maximal
      inhibition induced by the agents, both in the absence and presence of placental
      tissues in iNOS KO and wild-type mice. CONCLUSION: LPS induces PG production in
      mice myometrium that is not dependent on the integrity of iNOS, while LPS could
      induce pathophysiological iNOS obstruct uterine quiescence by physiological iNOS.
      Infection affects uterine contractile activity through PG production, as well as
      through placental and genetic factors. NO may be a double-edged sword in pregnant
      mice myometrium.

PMID- 22380702
TI  - Effects of pulmonary acid aspiration on the lungs and extra-pulmonary organs: a
      randomized study in pigs.
AB  - INTRODUCTION: There is mounting evidence that injury to one organ causes indirect
      damage to other organ systems with increased morbidity and mortality. The aim of
      this study was to determine the effects of acid aspiration pneumonitis (AAP) on
      extrapulmonary organs and to test the hypothesis that these could be due to
      circulatory depression or hypoxemia. METHODS: Mechanically ventilated
      anesthetized pigs were randomized to receive intrabronchial instillation of
      hydrochloric acid (n = 7) or no treatment (n = 7). Hydrochloric acid (0.1 N, pH
      1.1, 2.5 ml/kg BW) was instilled into the lungs during the inspiratory phase of
      ventilation. Hemodynamics, respiratory function and computer tomography (CT)
      scans of lung and brain were followed over a four-hour period. Tissue samples of
      lung, heart, liver, kidney and hippocampus were collected at the end of the
      experiment. RESULTS: Acid instillation caused pulmonary edema, measured as
      increased extravascular lung water index (ELWI), impaired gas exchange and
      increased mean pulmonary artery pressure. Gas exchange tended to improve during
      the course of the study, despite increasing ELWI. In AAP animals compared to
      controls we found: a) cardiac leukocyte infiltration and necrosis in the
      conduction system and myocardium; b) lymphocyte infiltration in the liver,
      spreading from the periportal zone with prominent areas of necrosis; c) renal
      inflammation with lymphocyte infiltration, edema and necrosis in the proximal and
      distal tubules; and d) a tendency towards more severe hippocampal damage (P >
      0.05). CONCLUSIONS: Acid aspiration pneumonitis induces extrapulmonary organ
      injury. Circulatory depression and hypoxemia are unlikely causative factors. ELWI
      is a sensitive bedside parameter of early lung damage.

PMID- 22380704
TI  - Graphite-coated paper as substrate for high sensitivity analysis in ambient
      surface-assisted laser desorption/ionization mass spectrometry.
AB  - In this work, an extremely simple and quite sensitive mass spectrometric method
      termed ambient surface-assisted laser desorption/ionization mass spectrometry
      (ambient SALDI-MS) was developed to analyze different kinds of compounds, just
      using a piece of graphite-coated paper for the sample introduction. This provides
      great advantage in simplifying the analysis process. The method is quite easy to
      use, and there is no need to worry about the source of graphite, that is, the
      brands or the types of pencil. And the whole process was carried out under
      atmospheric pressure, offering all the merits that could occur in ambient MS. The
      improved sensitivity of this method is mainly because of the graphite, which
      serves as energy-transfer medium to absorb the energy of the photons and release
      it to the analytes that are adsorbed on the graphite surface. Also, three
      different laser wavelengths (1064, 532, and 355 nm) was tested to investigate the
      desorption mechanism. Fifty-one compounds, with varied chemical structures, were
      tried to prove that this new method possessed universal applicability to detect
      different kinds of small organic molecules.

PMID- 22380705
TI  - Thought control strategies in adolescents: links with OCD symptoms and meta
      cognitive beliefs.
AB  - BACKGROUND: The perceived control of intrusive thoughts is important in our
      understanding of a variety of psychological disorders, but particularly in
      Obsessive Compulsive Disorder (OCD). Little research has explored thought control
      strategies in younger populations, despite the frequent onset of OCD in
      childhood. AIMS: This study examined thought control strategies and meta
      cognitive beliefs in relation to Obsessive Compulsive (OC) interference scores in
      an adolescent sample. METHOD: A non-referred sample of 151 adolescents aged 13-16
      completed the Thought Control Questionnaire, the Meta-Cognitions Questionnaire -
      Adolescent version, and the Leyton Obsessional Inventory - Child Version.
      RESULTS: Adolescents reported using distraction and worry as thought control
      strategies as much as adults, but social control and reappraisal less frequently,
      with adolescent males also reporting less use of punishment as a strategy. The
      strategies of worry and punishment, and positive beliefs about worry,
      uncontrollability and danger beliefs (UCD) and superstition punishment and
      responsibility beliefs (SPR) predicted OC interference scores. Furthermore, these
      meta-cognitive beliefs mediated the relationships between punishment and worry
      and OC interference scores. CONCLUSIONS: Given the similarities between our
      results and those from research exploring these variables in adults, it is
      proposed that cognitive behavioural models of OCD that have been developed in
      adult populations may be relevant to adolescents, but that meta-cognitive beliefs
      about superstition, punishment and responsibility may be important in
      adolescence.

PMID- 22380706
TI  - Late-evening snack with branched-chain amino acids improves liver function after
      radiofrequency ablation for hepatocellular carcinoma.
AB  - AIM:   This prospective study was designed to examine whether consumption of a
      branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening
      snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis
      (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular
      carcinoma (HCC). METHODS:   An equal number (10) of 30 LC patients who had
      undergone RFA for HCC was randomly assigned to a standard diet group (control)
      group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES
      BCAA) administration group. Liver function testing was performed and Child-Pugh
      scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12
      weeks post-RFA. RESULTS:   Compared to the control and M-BCAA groups, the LES
      BCAA group experienced a rapid and significant improvement in albumin and total
      serum bilirubin levels and in CPS that began during the initial post-RFA period.
      These results indicate that LES with BCAA supplementation significantly improved
      the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients
      experienced serious adverse effects, two patients who had been diagnosed with
      diabetes mellitus before undergoing RFA required blood sugar management to
      improve glycemic control and one subject withdrew due to supplement-induced
      vomiting. CONCLUSION:   LES with BCAA supplementation significantly and rapidly
      improves liver functioning and CPS in LC patients who have undergone RFA for HCC.
      Control of blood sugar levels is necessary when calorie-containing BCAA is
      administrated to LC patients with impaired glucose tolerance.

PMID- 22380707
TI  - Antioxidant, antimicrobial activity and inhibition of alpha-glucosidase activity
      by Betula alnoides Buch. bark extract and their relationship with polyphenolic
      compounds concentration.
AB  - Betula alnoides has been widely used in local traditional medicinal treatment for
      a variety of diseases, wounds and to cure diabetes. The air-dried, powdered (200
      g) bark was extracted with 80% methanol at room temperature. The combined 80%
      methanolic extract was partitioned with organic solvents to yield n-hexane, ethyl
      acetate (EtOAc), n-butanol (BuOH; water saturated), and aqueous fractions for the
      investigation of antioxidant and antimicrobiology and alpha-glucosidase activity
      effects (GAE) of B. alnoides. Antioxidant activity was studied by using
      antioxidant tests, including electron donation ability test, reducing power, and
      metal-chelating activity assay. Antioxidant, antimicrobial activity and alpha
      glucosidase inhibitory effect of 80% methanolic extracts and fractions derived
      from the bark of B. alnoides were evaluated and determined. The results showed
      that 80% methanolic extracts exhibited high 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      scavenging activity (80.68%). In addition, both the 80% methanolic extract and
      EtOAc fraction exhibited more potent reducing activity than did butylated
      hydroxyanisole (BHA) and trolox. The aqueous fraction had higher metal-chelating
      activity than other fractions. The EtOAc fraction had the highest phenolic and
      flavonoid content (217.73 +/- 1.02 mg GAE/g extract, and 38.42 +/- 1.87 mg QE/g
      extract, respectively). The 80% methanolic extract and EtOAc fraction showed
      higher levels of antimicrobial activity than did other fractions. The 80%
      methanolic extract had the most powerful alpha-glucosidase inhibitory effect
      (98.46%) at a concentration of 40 ug/mL. The results suggest that bark extracts
      of B. alnoides could be a potential source of natural antioxidants and for
      treating pathogenic diseases.

PMID- 22380709
TI  - Links between self-reported and laboratory behavioral impulsivity.
AB  - A major problem in the research considering impulsivity is the lack of mutual
      understanding on how to measure and define impulsivity. Our study examined the
      relationship between self-reported impulsivity, behavioral excitatory and
      inhibitory processes and time perception. Impulsivity--fast, premature,
      thoughtless or disinhibited behavior--was assessed in 58 normal, healthy
      participants (30 men, mean age 21.9 years). Self-reported impulsivity as measured
      by Adaptive and Maladaptive Impulsivity Scale (AMIS) and behavioral excitatory
      and inhibitory processes as measured by Stop Signal Task were not directly
      related. Time perception, measured by the retrospective Time Estimation Task, was
      related to both. The length of the perceived time interval was positively
      correlated to AMIS Disinhibition subscale and negatively to several Stop Signal
      Task parameters. The longer subjects perceived the duration to last, the higher
      was their score on Disinhibition scale and the faster were their reactive
      responses in the Stop Signal Task. In summary our findings support the idea of
      cognitive tempo as a possible mechanism underlying impulsive behavior.

PMID- 22380708
TI  - Peptidyl 3-hydroxyproline binding properties of type I collagen suggest a
      function in fibril supramolecular assembly.
AB  - Proline residues in collagens are extensively hydroxylated post-translationally.
      A rare form of this modification, (3S,2S)-l-hydroxyproline (3Hyp), remains
      without a clear function. Disruption of the enzyme complex responsible for prolyl
      3-hydroxylation results in severe forms of recessive osteogenesis imperfecta
      (OI). These OI types exhibit a loss of or reduction in the level of 3
      hydroxylation at two proline residues, alpha1(I) Pro986 and alpha2(I) Pro707.
      Whether the resulting brittle bone phenotype is caused by the lack of the 3
      hydroxyl addition or by another function of the enzyme complex is unknown. We
      have speculated that the most efficient mechanism for explaining the chemistry of
      collagen intermolecular cross-linking is for pairs of collagen molecules in
      register to be the subunit that assembles into fibrils. In this concept, the
      exposed hydroxyls from 3Hyp are positioned within mutually interactive binding
      motifs on adjacent collagen molecules that contribute through hydrogen bonding to
      the process of fibril supramolecular assembly. Here we report observations on the
      physical binding properties of 3Hyp in collagen chains from experiments designed
      to explore the potential for interaction using synthetic collagen-like peptides
      containing 3Hyp. Evidence of self-association was observed between a synthetic
      peptide containing 3Hyp and the CB6 domain of the alpha1(I) chain, which contains
      the single fully 3-hydroxylated proline. Using collagen from a case of severe
      recessive OI with a CRTAP defect, in which Pro986 was minimally 3-hydroxylated,
      such binding was not observed. Further study of the role of 3Hyp in
      supramolecular assembly is warranted for understanding the evolution of tissue
      specific variations in collagen fibril organization.

PMID- 22380711
TI  - Identification of novel antimalarial chemotypes via chemoinformatic compound
      selection methods for a high-throughput screening program against the novel
      malarial target, PfNDH2: increasing hit rate via virtual screening methods.
AB  - Malaria is responsible for approximately 1 million deaths annually; thus,
      continued efforts to discover new antimalarials are required. A HTS screen was
      established to identify novel inhibitors of the parasite's mitochondrial enzyme
      NADH:quinone oxidoreductase (PfNDH2). On the basis of only one known inhibitor of
      this enzyme, the challenge was to discover novel inhibitors of PfNDH2 with
      diverse chemical scaffolds. To this end, using a range of ligand-based
      chemoinformatics methods, ~17000 compounds were selected from a commercial
      library of ~750000 compounds. Forty-eight compounds were identified with PfNDH2
      enzyme inhibition IC(50) values ranging from 100 nM to 40 MUM and also displayed
      exciting whole cell antimalarial activity. These novel inhibitors were identified
      through sampling 16% of the available chemical space, while only screening 2% of
      the library. This study confirms the added value of using multiple ligand-based
      chemoinformatic approaches and has successfully identified novel distinct
      chemotypes primed for development as new agents against malaria.

PMID- 22380712
TI  - Celastrol analogues as inducers of the heat shock response. Design and synthesis
      of affinity probes for the identification of protein targets.
AB  - The natural product celastrol (1) possesses numerous beneficial therapeutic
      properties and affects numerous cellular pathways. The mechanism of action and
      cellular target(s) of celastrol, however, remain unresolved. While a number of
      studies have proposed that the activity of celastrol is mediated through reaction
      with cysteine residues, these observations have been based on studies with
      specific proteins or by in vitro analysis of a small fraction of the proteome. In
      this study, we have investigated the spatial and structural requirements of
      celastrol for the design of suitable affinity probes to identify cellular binding
      partners of celastrol. Although celastrol has several potential sites for
      modification, some of these were not synthetically amenable or yielded unstable
      analogues. Conversion of the carboxylic acid functionality to amides and long
      chain analogues, however, yielded bioactive compounds that induced the heat shock
      response (HSR) and antioxidant response and inhibited Hsp90 activity. This led to
      the synthesis of biotinylated celastrols (23 and 24) that were used as affinity
      reagents in extracts of human Panc-1 cells to identify Annexin II, eEF1A, and
      beta-tubulin as potential targets of celastrol.

PMID- 22380713
TI  - Treslin, DUE-B, and GEMC1 cannot complement Sld3 mutants in fission yeast.
AB  - Initiation of DNA replication in eukaryotes is an evolutionarily conserved
      process that involves two distinct steps: the formation of prereplication
      complexes at replication origins in G1 and the assembly of preinitiation
      complexes (pre-ICs) in S phase, which leads to activation of the replication
      helicase. For the assembly of pre-ICs in yeast, formation of the Sld2-Dpb11-Sld3
      complex is a critical event that requires phosphorylation of Sld2 and Sld3 by
      cyclin-dependent kinase. In mammals, RecQL4 and TopBP1 are excellent ortholog
      candidates for Sld2 and Dpb11, respectively. In this past year, three TopBP1
      interacting proteins Treslin/Ticrr, GEMC1, and DUE-B have been identified in
      metazoans as possible functional orthologs of the yeast Sld3. To test this
      hypothesis, we carried out several complementation tests in fission yeast. The
      proteins were expressed at various levels in the temperature-sensitive sld3-10
      mutant and in cells that lack endogenous Sld3. Our result showed that none of
      these metazoan proteins could rescue growth defect of the sld3 mutants. Although
      the result may have several interpretations, it is possible that the helicase
      activation in mammals has diverged in complexity during evolution from that in
      yeasts and may involve multiple players that interact with TopBP1.

PMID- 22380714
TI  - A delayed granulomatous reaction to a cosmetic tattoo of the eyebrows: a report
      of total regression after intralesional corticosteroid injections.

PMID- 22380715
TI  - Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an
      estimation based on WHO mortality data, a systematic literature review and data
      from the CRASH-2 trial.
AB  - BACKGROUND: The CRASH-2 trial showed that early administration of tranexamic acid
      (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from
      the CRASH-2 trial, global mortality data and a systematic literature review, we
      estimated the number of premature deaths that might be averted every year
      worldwide through the use of TXA. METHODS: We used CRASH-2 trial data to examine
      the effect of TXA on death due to bleeding by geographical region. We used WHO
      mortality data (2008) and data from a systematic review of the literature to
      estimate the annual number of in-hospital trauma deaths due to bleeding. We then
      used the relative risk estimates from the CRASH-2 trial to estimate the number of
      premature deaths that could be averted if all hospitalised bleeding trauma
      patients received TXA within one hour of injury, and within three hours of
      injury. Sensitivity analyses were used to explore the effect of uncertainty in
      the parameter estimates and the assumptions made in the model. RESULTS: There is
      no evidence that the effect of TXA on death due to bleeding varies by
      geographical region (heterogeneity p = 0.70). Based on WHO data and our
      systematic literature review, we estimate that each year worldwide there are
      approximately 400,000 in-hospital trauma deaths due to bleeding. If patients
      received TXA within one hour of injury then approximately 128,000 (uncertainty
      range [UR] ~ 72,000 to 172,000) deaths might be averted. If patients received TXA
      within three hours of injury then approximately 112,000 (UR ~ 68,000 to 148,000)
      deaths might be averted. Country specific estimates show that the largest numbers
      of deaths averted would be in India and China. CONCLUSIONS: The use of TXA in the
      treatment of traumatic bleeding has the potential to prevent many premature
      deaths every year. A large proportion of the potential health gains are in low
      and middle income countries.

PMID- 22380717
TI  - Cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics in patients with
      glomerulonephritis secondary to lupus and small vessel vasculitis.
AB  - AIMS: Cyclophosphamide, the precursor to the active 4-hydroxycyclophosphamide, is
      used in active glomerulonephritis despite limited pharmacokinetics data. The
      pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were
      evaluated. The influence of laboratory and pharmacogenomic covariates on
      pharmacokinetics was evaluated as a secondary aim. METHODS: Glomerulonephritis
      patients (n = 23) participated in a pharmacokinetic evaluation. Blood was
      serially collected and assayed for cyclophosphamide and 4-hydroxycyclophosphamide
      by LC/MS methods. Kidney function, serum albumin and polymorphisms in drug
      metabolism or transport genes were evaluated. Analyses included non-compartmental
      pharmacokinetics and parametric and non-parametric statistics. RESULTS: The mean
      area under the plasma concentration-time curve (AUC(0,infinity)) data were
      110,100 +/- 42,900 ng ml(-1) h and 5388 +/- 2841 ng ml(-1) h for cyclophosphamide
      and 4-hydroxycyclophosphamide, respectively. The mean metabolic ratio was 0.06 +/
      0.04. A statistically significant relationship was found between increased serum
      albumin and increased half-life (0.584, P = 0.007, 95% CI 0.176, 0.820) and a
      borderline relationship with AUC(0,infinity) (0.402, P = 0.079, 95% CI -0.064,
      0.724) for 4-hydroxycyclophosphamide. Covariate relationships that trended toward
      significance for cyclophosphamide included decreased serum albumin and increased
      elimination rate constant (-0.427, P = 0.061, 95% CI 0.738, 0.034), increased
      urinary protein excretion and increased AUC(0,infinity) (-0.392, P = 0.064, 95%
      CI -0.699 to 0.037), decreased C(max) (0.367, P = 0.085, 95% CI -0.067, 0.684)
      and decreased plasma clearance (-0.392, P = 0.064, 95% CI -0.699, 0.037).
      CYP2B6*9 variants vs. wildtype were found to have decreased elimination rate
      constant (P = 0.0005, 95% CI 0.033, 0.103), increased V(d) (P = 0.0271, 95% CI 
      57.5, -4.2) and decreased C(max) (P = 0.0176, 95% CI 0.696, 6179) for
      cyclophosphamide. ABCB1 C3435T variants had a borderline decrease in
      cyclophosphamide elimination rate constant (P = 0.0858; 95% CI -0.005, 0.102).
      CONCLUSIONS: Pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide
      in patients with lupus nephritis and small vessel vasculitis are similar.
      Clinical and pharmacogenetic covariates alter disposition of cyclophosphamide and
      4-hydroxycyclophosphamide. Clinical findings of worsened glomerulonephritis lead
      to increased exposure to cyclophosphamide vs. the active 4
      hydroxycyclophosphamide, which could have relevance in terms of clinical
      efficacy. The CYP2B6*9 and ABCB1 C3435T polymorphisms alter the pharmacokinetics
      of cyclophosphamide and 4-hydroxycyclophosphamide in glomerulonephritis.

PMID- 22380719
TI  - Lipschutz ulcers in twin sisters.
AB  - Lipschutz ulcer (LU) is an uncommon condition that usually affects prepubertal
      and pubertal girls. It can be misdiagnosed as a sexually transmitted disease or
      even as a sign of child abuse, causing great anxiety to patients and their
      families. We present two cases of LU consecutively affecting twin sisters. To our
      knowledge, this is the first case in two family members, supporting infectious
      transmission. We propose airborne transmission as the most probable cause in our
      cases.

PMID- 22380718
TI  - Exploring the interpersonal-, organization-, and system-level factors that
      influence the implementation and use of an innovation-synoptic reporting-in
      cancer care.
AB  - BACKGROUND: The dominant method of reporting findings from diagnostic and
      surgical procedures is the narrative report. In cancer care, this report
      inconsistently provides the information required to understand the cancer and
      make informed patient care decisions. Another method of reporting, the synoptic
      report, captures specific data items in a structured manner and contains only
      items critical for patient care. Research demonstrates that synoptic reports
      vastly improve the quality of reporting. However, synoptic reporting represents a
      complex innovation in cancer care, with implementation and use requiring
      fundamental shifts in physician behaviour and practice, and support from the
      organization and larger system. The objective of this study is to examine the key
      interpersonal, organizational, and system-level factors that influence the
      implementation and use of synoptic reporting in cancer care. METHODS: This study
      involves three initiatives in Nova Scotia, Canada, that have implemented synoptic
      reporting within their departments/programs. Case study methodology will be used
      to study these initiatives (the cases) in-depth, explore which factors were
      barriers or facilitators of implementation and use, examine relationships amongst
      factors, and uncover which factors appear to be similar and distinct across
      cases. The cases were selected as they converge and differ with respect to
      factors that are likely to influence the implementation and use of an innovation
      in practice. Data will be collected through in-depth interviews, document
      analysis, observation of training sessions, and examination/use of the synoptic
      reporting tools. An audit will be performed to determine/quantify use. Analysis
      will involve production of a case record/history for each case, in-depth analysis
      of each case, and cross-case analysis, where findings will be compared and
      contrasted across cases to develop theoretically informed, generalisable
      knowledge that can be applied to other settings/contexts. Ethical approval was
      granted for this study. DISCUSSION: This study will contribute to our knowledge
      base on the multi-level factors, and the relationships amongst factors in
      specific contexts, that influence implementation and use of innovations such as
      synoptic reporting in healthcare. Such knowledge is critical to improving our
      understanding of implementation processes in clinical settings, and to helping
      researchers, clinicians, and managers/administrators develop and implement ways
      to more effectively integrate innovations into routine clinical care.

PMID- 22380720
TI  - GluA and GluN receptors regulate the surface density of GluN receptor subunits in
      cultured neocortical interneurons.
AB  - J. Neurochem. (2012) 121, 597-606. ABSTRACT: In cultured rat neocortical
      interneurons, we have studied the effect of long-term application of NMDA or AMPA
      on the surface density of the NMDA (GluN) receptor subunits GluN1 and GluN2B.
      Stimulation of Ca(2+) -permeable AMPA (GluA) receptors located on the
      interneurons decreased the response of GluN receptors. The reduction was caused
      by a decrease in the surface density of GluN1/GluN2B subunits. In contrast,
      stimulation of GluN receptors located on the interneurons enhanced the surface
      density of GluN1/GluN2B subunits. Both effects could be induced by network
      activation.

PMID- 22380721
TI  - Thioarsenate transformation by filamentous microbial mats thriving in an
      alkaline, sulfidic hot spring.
AB  - Thioarsenates dominate arsenic speciation in sulfidic geothermal waters, yet
      little is known about their fate in the environment. At Conch Spring, an alkaline
      hot spring in Yellowstone National Park, trithioarsenate transforms to arsenate
      under increasingly oxidizing conditions along the drainage channel, accompanied
      by an initial increase, then decrease of monothioarsenate and arsenite. On-site
      incubation tests were conducted using sterile-filtered water with and without
      addition of filamentous microbial mats from the drainage channel to distinguish
      the role of abiotic and biotic processes for arsenic species transformation.
      Abiotically, trithioarsenate was desulfidized to arsenate coupled to sulfide
      oxidation. Monothioarsenate, however, was inert. Biotic incubations proved that
      the intermediate accumulation of arsenite in the drainage channel is microbially
      catalyzed. In the presence of sulfide, microbially enhanced sulfide oxidation
      coupled to reduction of arsenate to arsenite could simply enhance abiotic
      desulfidation of trithioarsenate and potentially also monothioarsenate. However,
      we were also able to show, in sulfide-free medium, direct microbial
      transformation of monothioarsenate to arsenate. Some arsenite formed
      intermediately, which was subsequently also microbially oxidized to arsenate.
      This study is the first evidence for microbially mediated thioarsenate species
      transformation by (hyper)thermophilic prokaryotes.

PMID- 22380722
TI  - Graphene-graphite oxide field-effect transistors.
AB  - Graphene's high mobility and two-dimensional nature make it an attractive
      material for field-effect transistors. Previous efforts in this area have used
      bulk gate dielectric materials such as SiO(2) or HfO(2). In contrast, we have
      studied the use of an ultrathin layered material, graphene's insulating analogue,
      graphite oxide. We have fabricated transistors comprising single or bilayer
      graphene channels, graphite oxide gate insulators, and metal top-gates. The
      graphite oxide layers show relatively minimal leakage at room temperature. The
      breakdown electric field of graphite oxide was found to be comparable to SiO(2),
      typically ~1-3 * 10(8) V/m, while its dielectric constant is slightly higher,
      kappa ~ 4.3.

PMID- 22380723
TI  - Psychological predictors of dietary intentions in pregnancy.
AB  - BACKGROUND: Consuming a healthy diet in pregnancy has the potential to improve
      obstetric outcome, including minimising the risk of macrosomia. Effective
      promotion of dietary change depends on identifying and targeting determinants of
      gestational diet. The present study aimed to model psychological predictors of
      intentions to reduce intake of high-fat and high-sugar foods, and increase fruit
      and vegetable consumption, among pregnant women. METHODS: One hundred and three
      pregnant women completed questionnaire measures of intentions to modify the
      consumption of the target foods, current intake, perceived vulnerability to and
      severity of adverse outcomes of unhealthful consumption of these foods (i.e.
      'threat'), benefits of dietary change to mother and baby, barriers to dietary
      changes, and social approval for dietary change ('subjective norms'). A cross
      sectional design was used. Logistic regression analyses were undertaken to model
      dietary change intentions. RESULTS: Participants who reported excessive current
      intake of high-fat and high-sugar foods were more likely to intend to reduce the
      intake of these foods. Perceived benefits for mother and baby enhanced intentions
      to eat more fruit and vegetables and eat less high-fat, and marginally
      significantly increased high-sugar reduction intentions. There were no effects of
      threat, barriers or subjective norms. CONCLUSIONS: Lack of effects for barriers,
      threat and subjective norms may indicate that pregnant women discount barriers to
      health-promoting behaviour, understand the threat posed by unhealthy eating and
      perceive social approval from others. Dietary change interventions for pregnant
      women should emphasise likely positive outcomes for both mother and child.

PMID- 22380724
TI  - Decreased expressions of vascular endothelial growth factor and visfatin in the
      placental bed of pregnancies complicated by preeclampsia.
AB  - AIM: The aim of the present study was to examine the expression of vascular
      endothelial growth factor (VEGF) and visfatin in the third trimester placental
      bed of pregnancies with and without preeclampsia (PE). MATERIAL AND METHODS: The
      study group consisted of placental bed biopsy tissues obtained from pregnancies
      with (n = 20) and without (n = 20) PE. The normotensive controls without PE were
      matched for gestational age at delivery with patients with PE. The expression of
      VEGF and visfatin in the placental bed tissues were evaluated using reverse
      transcriptase-polymerase chain reaction (RT-PCR), real-time polymerase chain
      reaction (PCR), immunohistochemistry and Western blot. RESULTS: There was no
      statistical difference between the PE group and the normotensive control group in
      age and body mass index (BMI). The expression of VEGF and visfatin was
      significantly decreased in the PE group compared with the normotensive control
      group (P < 0.05). CONCLUSION: This study showed decreased expressions of VEGF and
      visfatin in the third trimester placental bed of pregnancies with PE compared
      with the normotensive controls. This result suggests that decreased expression of
      these angiogenic factors in placental bed may be associated with the pathogenesis
      of PE.

PMID- 22380725
TI  - Is there a relationship between the playing position of soccer players and their
      food and macronutrient intake?
AB  - Many authors have proposed the necessity of the design and implementation of
      dietary and nutrition education programs for soccer players, although little
      information is available about the determinants of food selection and nutrient
      intake. The aim of this study was to evaluate the nutritional intake and eating
      patterns of soccer players according to their playing position in the team.
      Eighty-seven young male soccer players (aged 16-21 years) were recruited from the
      junior teams of a Spanish First Division Soccer League Club and divided into 6
      positional categories (goalkeepers, full-backs, centre-backs, midfielders,
      wingers, and forwards). Body composition (height, weight, and body fat),
      performance in soccer-specific tests (jumping, sprinting, and intermittent
      endurance), and dietary intake (weighed food intake method) were assessed. A
      spontaneous higher carbohydrate intake was observed for full-backs, midfielders,
      and wingers (g.kg(-1) body mass: 4.9 +/- 1.0, 4.9 +/- 1.3, 4.9 +/- 0.8; % of
      energy intake: 47 +/- 5, 46 +/- 6, 46 +/- 4), compared with goalkeepers and
      centre-backs (g.kg(-1) of body mass: 3.9 +/- 1.0, 4.3 +/- 1.1; % of energy
      intake: 44 +/- 3, 42 +/- 4). These differences were related to food selection
      patterns, and a higher contribution to daily energy intake of cereals,
      derivatives, and potatoes was observed between full-backs compared with
      goalkeepers and centre-backs (33% vs. 27% and 25%). The magnitude of these
      differences is limited considering the whole diet, and an inadequate nutrient
      intake were observed in most individuals of every group. The design and
      implementation of nutrition intervention programs, taking into consideration
      positional differences in nutritional intake, would be useful for these players.

PMID- 22380726
TI  - Repeated high-intensity Wingate cycle bouts influence markers of lymphocyte
      migration but not apoptosis.
AB  - Studies have shown significant changes in lymphocytes during continuous exercise,
      but little has been shown on the effect of repeated high intensity bouts. This
      study was designed to examine the effect of repeated intermittent bouts on
      lymphocyte subset cell count, apoptosis, and migration. A series of 6 Wingate
      anaerobic cycle tests were performed by participants (N = 8) with blood samples
      attained before, immediately following, and after a designated recovery period
      (excess postexercise oxygen consumption (EPOC)) to observe lymphocyte changes.
      Lymphocyte subsets (CD4+, CD4/CD45RA+, CD8+, CD8+/CD45RA+, CD19+) were assessed
      for apoptosis (annexin V+) and cellular migration (CX(3)CR1). Our results
      indicate that the CD8+ and CD8+/CD45RA+ subsets were significantly influenced by
      the repetitive Wingate cycling protocol such that cell counts increased with
      exercise, and then decreased at EPOC termination (p = 0.016). The observed
      postexercise decrease in CD8+ and CD8+/CD45RA+ cells was accompanied by a
      significant change in the CX(3)CR1 cell migration receptor (p = 0.019), but not
      apoptosis (p = 0.87). This indicates that with repetitive high-intensity cycling,
      the response in CD8+ cells following the bout is likely due to cell migration
      rather than cell death.

PMID- 22380727
TI  - Gender-dependent effects of high-fat lard diet on cardiac function in C57Bl/6J
      mice.
AB  - Increased availability of fatty acids released from insulin-resistant adipose
      tissue may lead to excess fatty acid uptake in nonadipose organs, including the
      heart. Accumulation of toxic fatty acid intermediates may affect cardiac
      function. Our aim was to identify to which extent high-fat diet feeding leads to
      alterations in cardiac function and whether this depends on gender and (or)
      duration of high-fat diet feeding. Male and female C57Bl/6J mice (n = 8 per
      group) of 12 to 16 weeks old were fed a low-fat (10% energy) or high-fat (45%
      energy) lard diet for 6 or 12 weeks. Plasma lipid levels, echocardiography, and
      left ventricular pressure-volume relationships were obtained at 2, 1, and 0 weeks
      before termination, respectively. In both male and female mice, the high-fat diet
      increased body weight and plasma lipid content. At 10 weeks, significant
      increases were observed for plasma total cholesterol (males: +44%; females:
      +86%), phospholipids (+16% and +34%), and triglycerides (+27% and +53%) (all p <
      0.001). In male mice, but not in female mice, the high-fat diet significantly
      affected cardiac function at 12 weeks with increased end-systolic volume (25.4 +/
      6.2 vs. 17.0 +/- 6.7 uL, p < 0.05), increased end-systolic pressure (72.1 +/-
      6.9 vs. 63.6 +/- 6.9 mm Hg, p < 0.01), and decreased ejection fraction (61.2% +/-
      4.5% vs. 68.1% +/- 3.7%, p < 0.01), indicating reduced systolic function.
      Multiple linear regression analysis indicated a significant diet-gender
      interaction for end-systolic volume and ejection fraction. In conclusion, high
      fat diet feeding increased body weight and plasma lipid levels in male and in
      female mice, but resulted in impairment of cardiac function only in males.

PMID- 22380728
TI  - Intercostal insertion of Veress needle for canine laparoscopic procedures: a
      cadaver study.
AB  - OBJECTIVE: To record and compare the frequency of organ penetration after
      insertion of a Veress needle (VN) in 6 different intercostal spaces (ICS) for
      creation of pneumoperitoneum in canine cadavers. STUDY DESIGN: Descriptive study.
      ANIMALS: Canine cadavers (n = 15). METHODS: In 15 cadavers positioned in dorsal
      recumbency, VN insertion in the right and left 8th-10th ICS was performed, the
      abdomen insufflated, and VN position and any visceral penetration recorded. The
      frequency of viscus penetration was assessed in all insertion sites. RESULTS: In
      cadavers, the right 9th ICS was associated with the lowest number of organ
      penetrations after VN insertion. CONCLUSION: In cadavers, the position associated
      with the lowest frequency of penetrating any intraabdominal structure was the 9th
      ICSon the right side.

PMID- 22380729
TI  - Bone marrow cells stained by azide-conjugated Alexa fluors in the absence of an
      alkyne label.
AB  - Thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) has recently been introduced as
      an alternative to 5-bromo-2-deoxyuridine (BrdU) for cell labeling and tracking.
      Incorporation of EdU into replicating DNA can be detected by azide-conjugated
      fluors (eg, Alexa-azide) through a Cu(i)-catalyzed click reaction between EdU's
      alkyne moiety and azide. While this cell labeling method has proven to be
      valuable for tracking transplanted stem cells in various tissues, we have found
      that some bone marrow cells could be stained by Alexa-azide in the absence of EdU
      label. In intact rat femoral bone marrow, ~3% of nucleated cells were false
      positively stained, and in isolated bone marrow cells, ~13%. In contrast to true
      positive stains, which localize in the nucleus, the false-positive stains were
      cytoplasmic. Furthermore, while true-positive staining requires Cu(i), false
      positive staining does not. Reducing the click reaction time or reducing the
      Alexa-azide concentration failed to improve the distinction between true- and
      false-positive staining. Hematopoietic and mesenchymal stem cell markers CD34 and
      Stro-1 did not co-localize with the false-positively stained cells, and these
      cells' identity remains unknown.

PMID- 22380730
TI  - Measurement of drug lipophilicity and pKa using acoustics.
AB  - Lipophilicity of chemicals and drug candidates is normally described in terms of
      octanol/water partitioning and log P. We investigated an alternate approach to
      lipophilicity determination using a mimic of an alkyl alcohol with compound
      partitioning quantified using acoustic sensing. A self-assembled monolayer
      composed of HSC(10)(CH(2)CH(2)O)(6)C(18) was formed on planar gold electrodes of
      a piezoelectric acoustic sensor. The system was challenged with compounds
      covering a 4-log range of log D values. As compounds partitioned in the
      interfacial layer, changes in sensor resonant frequency were found to correlate
      with compound partition coefficients (log P) and with distribution coefficients
      (log D). Linear concordance (R(2) = 0.933) was established between log(-dF/M(w)t)
      and log P and with log D in both water and biological buffers at variant pH (pH
      5.2 to 7.8). In turn, drug pK(a) could be determined by profiling log D changes
      during pH titration. The lipophilicity/pH profile of a weakly basic drug
      (quinine; pK(a) = 7.95) was sigmoidal with respect to -dF/M(w) values, with a
      profile inverse to that of a weakly acidic drug (naproxen; pK(a) = 4.15).

PMID- 22380731
TI  - Chemoenzymatic synthesis of poly(L-alanine) in aqueous environment.
AB  - L-alanine ethyl ester was polymerized into poly(L-alanine) (polyAla), one of the
      insoluble polypeptides, by papain in aqueous buffer at varying pH. At neutral pH,
      a maximum chain length of 11 repeats was observed. These polymers were dominated
      by random coiled structure and demonstrated a lack of patterned macromolecular
      assembly. Under alkaline conditions, longer polymer chain lengths were achieved,
      and the maximum chain length was 16 repeats. These longer chains showed distinct
      beta-sheet formation and were capable of fibril assembly. The present study
      reports on chemoenzymatic synthesis of a hydrophobic homopolypeptide under
      aqueous conditions as well as demonstrates a chain length dependency of secondary
      structure formation and macromolecular assembly of chemoenzymatically synthesized
      polyAla, providing a new insight into material design of polypeptide.

PMID- 22380732
TI  - Microstructural evaluation of boron free and boron containing heat-treated Ti
      35Nb-7.2Zr-5.7Ta alloy.
AB  - The microstructure of Ti-35Nb-7.2Zr-5.7Ta (TNZT) and Ti-35Nb-7.2Zr-5.7Ta-0.5B
      (TNZTB) alloys under different heat treatment conditions has been analyzed. The
      solution-treated and water-quenched TNZT sample consists mainly of beta phase
      with a very small amount of fine athermal omega precipitate. Precipitation of
      alpha can be observed when solution-treated samples are directly aged at 580
      degrees C for 8 h. The microstructure of the samples subjected to single-stage
      aging at 300 degrees C or 400 degrees C consists of omega precipitates in
      equiaxed beta grains. Second stage aging at 580 degrees C for 8 h after first
      stage of aging at 300 degrees C or 400 degrees C results in the replacement of
      omega precipitates by secondary alpha. In all of these samples, the amount of
      omega or alpha phase was very small, and therefore they could not be detected by
      X-ray diffraction studies. However, analysis of selected area diffraction
      patterns obtained from transmission electron microscopy studies confirms their
      presence. The addition of boron leads to the formation of dispersed precipitates
      of TiB in the beta matrix of the TNZT alloy and also refines the beta grains in
      the microstructure. However, other microstructural features of the TNZTB alloy
      are similar to those of the TNZT alloy.

PMID- 22380733
TI  - Prion infected rhesus monkeys to study differential transcription of Alu DNA
      elements and editing of Alu transcripts in neuronal cells and blood cells.
AB  - BACKGROUND: Rhesus monkeys were used as a non-human primate model to study small
      non-coding RNA after infection with human sporadic and variant Creutzfeldt-Jakob
      prions. METHODS: Tissue-specific Alu DNA element transcription and editing of
      transcripts were assessed in neuronal - and blood cells (Buffy Coat). RESULTS:
      Tissue/cell-specific transcription and editing patterns were obtained. Active Alu
      DNA elements belonged to several Alu DNA families, they could be located on
      several chromosomes, and their genomic sites were identified. Deamination by
      adenosine deaminase acting on RNA and apolipoprotein B editing complex was found.
      CONCLUSIONS: Different Alu transcription and editing programmes exist and may
      depend on the infection status.

PMID- 22380734
TI  - Potential association of DDR1 genetic variant with FEV1 decline by aspirin
      provocation in asthmatics.
AB  - BACKGROUND: The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned
      within the major histocompatibility complex (MHC) region which plays an important
      role in the immune system. In addition, DDR1 has been elucidated to be
      downregulated during the epithelial-mesenchymal transition of bronchial
      epithelium. OBJECTIVE: To investigate the potential genetic associations between
      DDR1 and aspirin-exacerbated respiratory disease (AERD), this study conducted
      association studies of DDR1 single nucleotide polymorphisms (SNPs) with AERD and
      the obstructive symptom of forced expiratory volume in 1 s (FEV(1)) decline after
      aspirin provocation. METHODS: Nine common SNPs were genotyped in 93 AERD patients
      and 96 aspirin-tolerant asthma (ATA) controls. The genotype distributions of all
      loci were in Hardy-Weinberg equilibrium (HWE; p > .05). Results. In the results
      of logistic analyses using age, sex, smoking status, and atopy as covariates,
      DDR1 rs1264320 in the intronic region showed a potent association signal with
      FEV(1) decline by aspirin provocation in asthmatics of this study even after
      corrections for multiple testing (p = .003 and corrected p = .01). However, the
      variants of DDR1 were not significantly associated with the AERD development
      (corrected p > .05). On further comparison of FEV(1) decline by aspirin
      provocation between AERD and ATA, the variant rs1264320 was found to be
      associated with the FEV(1) decline of ATA rather than AERD. CONCLUSION: Despite
      the need for further functional evaluations and replications, we conclude that
      DDR1 polymorphisms are not likely to contribute to predispositions of AERD, but
      may be potentially associated with FEV(1) decline by aspirin provocation in
      asthmatics.

PMID- 22380735
TI  - Effectiveness of a community-based health promotion program targeting people with
      hypertension and high cholesterol.
AB  - The purpose of this study was to evaluate the effectiveness of a community-based
      health promotion program targeting people with hypertension and high cholesterol.
      A pre-experimental study was conducted. A total of 60 residents were recruited to
      participate. Participants were assessed at baseline and at a 6 month follow up at
      a regional hospital in northern Taiwan. The questionnaires used for data
      collection consisted of an assessment of self-efficacy, self-care activities,
      health outcomes, and physical fitness. Several teaching resources were used,
      including a DVD, a self-care booklet, group support (exercise and counseling
      sessions), and telephone follow up. A significant decrease in waist circumference
      (t = 2.20, P = 0.03) and high density lipoprotein-cholesterol level (t = 4.71, P
      < 0.00) was found at follow up. Moreover, the level of physical fitness activity,
      and sit-ups specifically (t = 3.10, P < 0.00), was increased. Participants also
      showed significant increases between baseline and 6 month follow up in their
      efficacy expectation score (t = -5.81, P < 0.00), outcome expectation scores (t =
      -4.76, P < 0.00) and self-care behavior scores (t = -2.78, P = 0.007). The
      community-based health promotion program is an effective means of helping people
      with hypertension and high cholesterol and should be instituted regularly and
      evaluated in clinical practice.

PMID- 22380736
TI  - Discovery of highly potent and selective pan-Aurora kinase inhibitors with
      enhanced in vivo antitumor therapeutic index.
AB  - Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell
      mitosis and cytokinesis. Currently a number of Aurora kinase inhibitors with
      different isoform selectivities are being evaluated in the clinic. Herein we
      report the discovery and characterization of 21c (AC014) and 21i (AC081), two
      structurally novel, potent, kinome-selective pan-Aurora inhibitors. In the human
      colon cancer cell line HCT-116, both compounds potently inhibit histone H3
      phosphorylation and cell proliferation while inducing 8N polyploidy. Both
      compounds administered intravenously on intermittent schedules displayed potent
      and durable antitumor activity in a nude rat HCT-116 tumor xenograft model and
      exhibited good in vivo tolerability. Taken together, these data support further
      development of both 21c and 21i as potential therapeutic agents for the treatment
      of solid tumors and hematological malignancies.

PMID- 22380739
TI  - Evaluation of perirenal fat as a predictor of cT 1a renal cortical neoplasm
      histopathology and surgical outcomes.
AB  - BACKGROUND AND PURPOSE: With the increasing detection of small renal cortical
      neoplasms (RCNs), the preoperative prediction of histopathology has become
      increasingly important. Because perirenal fat (PF) is known to be metabolically
      active, we evaluated PF as a predictor of renal tumor histopathology. PATIENTS
      AND METHODS: We retrospectively evaluated patients who underwent laparoscopic
      nephron-sparing procedures for cT(1a) RCN at two institutions. PF was measured
      using the digital measuring tool function on standard imaging software, at the
      level of the renal hilum as the perpendicular distance between the posterior
      surface of the kidney and the external margin of the psoas muscle. The Mann
      Whitney test and logistic regression were used to examine PF, selected
      demographic, clinical, and operative parameters, and their association with tumor
      histopathology. RESULTS: Data from 250 patients were included in this study.
      There were 157 (63%) men and 93 (37%) women with a median body mass index (BMI)
      of 28 kg/m(2). Median tumor size was 2.4 cm, and the median PF distance was 12
      mm. Significant correlations were noted between PF and sex and BMI. No
      significant correlations were found between PF and the operative parameters.
      Results of a multivariate logistic regression analysis revealed that PF (P<0.01),
      age (P<0.04), and tumor location (P<0.04) were significant predictors of clear
      cell renal-cell carcinoma (RCC) histopathology. CONCLUSIONS: In this study, PF,
      location of tumor, and age were significant predictors of clear-cell RCC
      histopathology. The correlation of PF and histopathology may be useful in
      preoperative decision-making and surgical planning in the management of small
      RCN.

PMID- 22380737
TI  - Allosteric tertiary interactions preorganize the c-di-GMP riboswitch and
      accelerate ligand binding.
AB  - Cyclic diguanylate (c-di-GMP) is a bacterial second messenger important for
      physiologic adaptation and virulence. Class-I c-di-GMP riboswitches are
      phylogenetically widespread and thought to mediate pleiotropic genetic responses
      to the second messenger. Previous studies suggest that the RNA aptamer domain
      switches from an extended free state to a compact, c-di-GMP-bound conformation in
      which two helical stacks dock side-by-side. Single molecule fluorescence
      resonance energy transfer (smFRET) experiments now reveal that the free RNA
      exists in four distinct populations that differ in dynamics in the extended and
      docked conformations. In the presence of c-di-GMP and Mg(2+), a stably docked
      population (>30 min) becomes predominant. smFRET mutant analysis demonstrates
      that tertiary interactions distal to the c-di-GMP binding site strongly modulate
      the RNA population structure, even in the absence of c-di-GMP. These allosteric
      interactions accelerate ligand recognition by preorganizing the RNA, favoring
      rapid c-di-GMP binding.

PMID- 22380740
TI  - Development of a phenol-enriched olive oil with both its own phenolic compounds
      and complementary phenols from thyme.
AB  - Besides affecting the oil's sensorial characteristics, the presence of herbs and
      spices has an impact on the nutritional value of the flavored oils. The aim of
      the study was to develop a new product based on the phenol-enrichment of a virgin
      olive oil with both its own phenolic compounds (secoiridoid derivatives) plus
      additional complementary phenols from thyme (flavonoids). We studied the effect
      of the addition of phenolic extracts (olive cake and thyme) on phenolic
      composition, oxidative stability, antioxidant activity, and bitter sensory
      attribute of olive oils. Results showed that flavonoids from thyme appeared to
      have higher transference ratios (average 89.7%) from the phenolic extract to oil,
      whereas secoiridoids from olive presented lower transference ratios (average
      35.3%). The bitter sensory attribute of the phenol-enriched oils diminished with
      an increase of the concentration of phenols from thyme, which might denote an
      improvement in the consumer acceptance.

PMID- 22380741
TI  - Overexpression of PDE2 or SSD1-V in Saccharomyces cerevisiae W303-1A strain
      renders it ethanol-tolerant.
AB  - Understanding the genetic basis of the yeast ability to proliferate and ferment
      in the presence of restrictive concentrations of ethanol is of importance to both
      science and technology. In this study, we searched for genes that improve ethanol
      tolerance in ethanol-sensitive strains. To screen for suppressors of ethanol
      sensitivity, we introduced a 2u-based genomic library, prepared from the ethanol
      tolerant yeast S288C, into the ethanol-sensitive strain W303-1A. Two genomic
      fragments from this library rescued the ethanol sensitivity of W303-1A. One
      contained the PDE2 gene, which when over-expressed, conferred ethanol tolerance.
      Surprisingly, the effect of PDE2 was not mediated via MSN2/MSN4 transcription
      factors, as it was able to improve ethanol tolerance in msn2Deltamsn4Delta
      strain. In the second genomic fragment, it was the N-terminal region of the SSD1
      gene that carried the ethanol-tolerant phenotype. The SSD1-V allele of the
      polymorphic SSD1 gene expressed from a low-copy number plasmid also resulted in
      the tolerant phenotype. Both SSD1 and PDE2 seemed to improve ethanol tolerance by
      maintaining robustness of the yeast cell wall.

PMID- 22380742
TI  - Evidence for decline in the incidence of cystic fibrosis: a 35-year observational
      study in Brittany, France.
AB  - BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder whose
      incidence has long been estimated as 1/2500 live births in Caucasians. Expanding
      implementation of newborn screening (NBS) programs now allows a better monitoring
      of the disease incidence, what is essential to make reliable predictions for
      disease management. This study assessed time trends in the birth incidence of CF
      over a long period (35 years: 1975-2009) in an area where CF is frequent
      (Brittany, France) and where NBS has been implemented for more than 20 years.
      METHODS: This study enrolled CF patients born in Brittany between January 1st
      1975 and December 31st 2009 (n = 483). Time trends in incidence were examined
      using Poisson regression and mainly expressed using the average percent change
      (APC). RESULTS: The average number of patients born each year declined from 18.6
      in the late 1970's (period 1975-79) to 11.6 nowadays (period 2005-09). The
      corresponding incidence rates dropped from 1/1983 to 1/3268, which represented a
      decline close to 40% between these two periods (APC = -39.3%, 95% CI = -55.8% to 
      16.7%, p = 0.0020). A clear breakpoint in incidence rate was observed at the end
      of the 1980's (p < 0.0001). However, the incidence rate has remained quite stable
      since that time (annual APC = -1.0%, 95% CI = -3.0% to 1.1%, p = 0.3516).
      CONCLUSIONS: This study provides an accurate picture of the evolution of the
      incidence of a genetic disease over a long period and highlights how it is
      influenced by the health policies implemented. We observed a 40% drop in
      incidence in our area which seems consecutive to the availability of prenatal
      diagnosis.

PMID- 22380743
TI  - Influence of adult age on the total and free clearance and protein binding of (R)
      and (S)-warfarin.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Hepatic drug clearance is thought to be
      reduced with age. However for highly protein bound drugs, which are cleared by
      capacity-limited metabolism, studies on total clearance have been conflicting.
      The hypothesis that protein binding decreases with age has been used to explain
      this. Warfarin is a highly protein bound drug, which is cleared by capacity
      limited metabolism. There are conflicting or little data on the relationship
      between adult age and total and free clearance and protein binding of (R)- and
      (S)-warfarin. WHAT THIS STUDY ADDS: In a clinical study of 72 patients (18-89
      years) on warfarin therapy, both total and free clearance of (R)-warfarin
      decreased with age. For (S)-warfarin there was a stronger signal of a decrease in
      free than total clearance. Protein binding was found not to correlate with age
      for (R)- and (S)-warfarin. In an ex vivo study, in which warfarin was spiked to
      plasma samples from 60 healthy subjects (19-87 years), no correlation between
      protein binding and age was found. These data support the hypothesis that hepatic
      drug clearance decreases with age. This should be taken into consideration when
      individualizing dosing, particularly in the elderly. AIMS: To test the hypothesis
      that the clearance (CL) of warfarin, a very highly protein bound drug with
      capacity-limited metabolism, decreases with age. METHODS: In a clinical study, a
      steady-state blood sample was taken from 72 patients (18-89 years) on routine
      treatment with warfarin. Concentrations of (R)- and (S)-warfarin were determined
      in plasma (total) and ultrafiltrate (free) by LC-MS/MS. Total and free CL and
      protein binding were determined and regressed against age and other covariates.
      In an ex vivo study, warfarin was spiked to plasma samples from 60 healthy
      subjects (19-87 years) and protein binding was regressed against age and other
      covariates. RESULTS: For (R)-warfarin a significant decrease with age was found
      for both total and free CL (P < 0.001). For (S)-warfarin there was a stronger
      signal of a decrease with age in free CL (P= 0.005) vs. total CL (P= 0.045). The
      decrease in CL of (R)- and (S)-warfarin was 0.3-0.5% per year. Other covariates
      influencing CL were lean body weight for both (R)- and (S)-warfarin and CYP2C9
      genotype and blood sampling time for (S)-warfarin. Protein binding of (R)- and
      (S)-warfarin was not found to change significantly with age in either the
      clinical or the spiked samples, despite a slight decrease in albumin
      concentration with age. CONCLUSIONS: These data support the hypothesis that the
      CL of (R)- and (S)-warfarin decreases with age. More accurate information was
      gained when measuring free CL for (S)-warfarin. Warfarin protein binding did not
      change significantly with age.

PMID- 22380745
TI  - Pressure support ventilation vs spontaneous ventilation via ProSealTM laryngeal
      mask airway in pediatric patients undergoing ambulatory surgery: a randomized
      controlled trial.
AB  - AIM: To investigate the advantages of using pressure support ventilation (PSV) vs
      spontaneous ventilation via ProSealTM laryngeal mask airway in children
      undergoing ambulatory surgery. BACKGROUND: In our ambulatory surgical unit, the
      use of unassisted spontaneous breathing via laryngeal mask airway is a common
      anesthetic technique during general anesthesia. However, this may be associated
      with inadequate ventilation. PSV is a ventilatory mode that is synchronized with
      the patient's respiratory effort and may improve gaseous exchange under general
      anesthesia. MATERIALS AND METHODS: After the approval from the ethics committee,
      a randomized controlled trial involving 24 pediatric patients was conducted in
      our ambulatory surgical unit. They were randomized into two groups, namely Group
      PSV (receiving PSV) and Group SV (unassisted spontaneous ventilation). Outcome
      measures included intraoperative respiratory and hemodynamic parameters as well
      as recovery room data. RESULTS: There were no significant differences in baseline
      characteristics between the two groups. Patients in Group PSV had lower ETCO(2)
      (42.8 +/- 5.8 vs 50.4 +/- 4.0, P = 0.001) and higher expiratory tidal volume per
      kg bodyweight (8.3 +/- 1.8 ml kg(-1) vs 5.8 +/- 0.8 ml kg(-1), P = 0.001)
      compared with patients in Group SV. There were no significant differences in
      other respiratory and hemodynamic parameters or recovery room data between the
      two groups. CONCLUSION: Pressure support ventilation via ProSealTM laryngeal mask
      airway during general anesthesia improves ventilation in pediatric patients
      undergoing ambulatory surgery. However, this did not translate to a difference in
      clinical outcome among our study patients.

PMID- 22380746
TI  - Anesthetic considerations in Netherton Syndrome.

PMID- 22380747
TI  - Plasma fluoride concentrations during prolonged administration of isoflurane to a
      pediatric patient requiring renal replacement therapy.

PMID- 22380748
TI  - Thermal injuries from the use of a forced-air warming device.

PMID- 22380749
TI  - The 'curare cleft' is not the first sign of respiratory effort.

PMID- 22380750
TI  - Pica: unusual intra-oral foreign body discovered after induction in a child.

PMID- 22380751
TI  - An uninvited guest in larynx: a case report.

PMID- 22380752
TI  - Tears at breakfast.

PMID- 22380753
TI  - Emission factors, size distributions, and emission inventories of carbonaceous
      particulate matter from residential wood combustion in rural China.
AB  - Published emission factors (EFs) often vary significantly, leading to high
      uncertainties in emission estimations. There are few reliable EFs from field
      measurements of residential wood combustion in China. In this study, 17 wood
      fuels and one bamboo were combusted in a typical residential stove in rural China
      to measure realistic EFs of particulate matter (PM), organic carbon (OC), and
      elemental carbon (EC), as well as to investigate the influence of fuel properties
      and combustion conditions on the EFs. Measured EFs of PM, OC, and EC (EF(PM),
      EF(OC), and EF(EC), respectively) were in the range of 0.38-6.4, 0.024-3.0, and
      0.039-3.9 g/kg (dry basis), with means and standard derivation of 2.2 +/- 1.2,
      0.62 +/- 0.64, and 0.83 +/- 0.69 g/kg, respectively. Shrubby biomass combustion
      produced higher EFs than tree woods, and both species had lower EFs than those of
      indoor crop residue burning (p < 0.05). Significant correlations between EF(PM),
      EF(OC), and EF(EC) were expected. By using a nine-stage cascade impactor, it was
      shown that size distributions of PM emitted from tree biomass combustions were
      unimodal with peaks at a diameter less than 0.4 MUm (PM(0.4)), much finer than
      the PM from indoor crop residue burning. Approximately 79.4% of the total PM from
      tree wood combustion was PM with a diameter less than 2.1 MUm (PM(2.1)). PM size
      distributions for shrubby biomasses were slightly different from those for tree
      fuels. On the basis of the measured EFs, total emissions of PM, OC, and EC from
      residential wood combustion in rural China in 2007 were estimated at about 303,
      75.7, and 92.0 Gg.

PMID- 22380754
TI  - Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: In vitro exposure of liver cells to high concentrations of free fatty
      acids (FFA) results in fat overload which promotes inflammatory and fibrogenic
      response similar to those observed in patients with Non-Alcoholic Fatty Liver
      Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of
      this event have not been fully characterized, we aimed to analyze the fibrogenic
      stimuli in a new in vitro model of NASH. METHODS: HuH7 cells were cultured for 24
      h in an enriched medium containing bovine serum albumin and increasing
      concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and
      oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and
      production of inflammatory and fibrogenic cytokines were measured. RESULTS: FFA
      induces a significant increment in the intracellular content of lipid droplets.
      The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor
      alpha was significantly increased. The protein level of interleukin-8 was also
      increased. Intracellular lipid accumulation was associated to a significant up
      regulation in the gene expression of transforming growth factor beta 1, alpha 2
      macroglobulin, vascular endothelial growth factor A, connective tissue growth
      factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis
      demonstrated a significant increment of early apoptosis and production of
      reactive oxygen species. CONCLUSIONS: The exposure of hepatocytes to fatty acids
      elicits inflammation, increase of oxidative stress, apoptosis and production of
      fibrogenic cytokines. These data support a primary role of FFA in the
      pathogenesis of NAFLD and NASH.

PMID- 22380755
TI  - Use of a laparoscopic retrieval device for urolith removal through a perineal
      urethrotomy.
AB  - OBJECTIVE: To report the use of a laparoscopic retrieval device for removal of
      uroliths via a perineal urethrotomy. STUDY DESIGN: Case report. ANIMALS: A 12
      year-old Konenklijk Warmbloed Paardenstamboek Nederland (KWPN) gelding and a 15
      year-old Holsteiner gelding. METHODS: Perineal urethrotomy was performed on 2
      standing sedated geldings and the urolith was removed using a laparoscopic
      retrieval device. RESULTS: In both cases, uroliths were removed successfully with
      no short- or long-term complications. The larger of the 2 uroliths measured 6 cm
      in length and 4.6 cm in width. CONCLUSIONS: Removal of a urolith via a perineal
      urethrotomy using a laparoscopic retrieval device was an expedient and minimally
      traumatic method that obviated the need for fragmentation before removal.

PMID- 22380756
TI  - Electron tunneling through ultrathin boron nitride crystalline barriers.
AB  - We investigate the electronic properties of ultrathin hexagonal boron nitride (h
      BN) crystalline layers with different conducting materials (graphite, graphene,
      and gold) on either side of the barrier layer. The tunnel current depends
      exponentially on the number of h-BN atomic layers, down to a monolayer thickness.
      Conductive atomic force microscopy scans across h-BN terraces of different
      thickness reveal a high level of uniformity in the tunnel current. Our results
      demonstrate that atomically thin h-BN acts as a defect-free dielectric with a
      high breakdown field. It offers great potential for applications in tunnel
      devices and in field-effect transistors with a high carrier density in the
      conducting channel.

PMID- 22380757
TI  - A meta-analytical review of the effects of elevated CO2 on plant-arthropod
      interactions highlights the importance of interacting environmental and
      biological variables.
AB  - We conducted the most extensive meta-analysis of plant and animal responses to
      elevated CO(2) to date. We analysed > 5000 data points extracted from 270 papers
      published between 1979 and 2009. We examined the changes in 19 animal response
      variables to the main effect of elevated CO(2). We found strong evidence for
      significant variation among arthropod orders and feeding guilds, including
      interactions in the direction of response. We also examined the main effects of
      elevated CO(2) on: six plant growth and allocation responses, seven primary
      metabolite responses, eight secondary metabolite responses, and four physical
      defence responses. We examined these response variable changes under two-way and
      three-way interactions between CO(2) and: soil nitrogen, ambient temperature,
      drought, light availability, photosynthetic pathway, reproductive system, plant
      growth rate, plant growth form, tissue type, and nitrogen fixation. In general we
      found smaller effect sizes for many response variables than have been previously
      reported. We also found that many of the oft-reported main effects of CO(2)
      obscure the presence of significant two- and three-way interactions, which may
      help better explain the relationships between the response variables and elevated
      CO(2).

PMID- 22380758
TI  - Variable phase dark-field contrast--a variant illumination technique for improved
      visualizations of transparent specimens.
AB  - Variable phase dark-field contrast has been developed as an illumination
      technique in light microscopy, which promises significant improvements and a
      higher variability in imaging of several transparent specimens. In this method, a
      phase contrast image is optically superimposed on a dark-field image so that a
      partial image based on the principal zeroth-order maximum (phase contrast)
      interferes with an image that is based on the secondary maxima (dark field). The
      background brightness and character of the resulting image can be continuously
      modulated from a phase-contrast-dominated to a dark-field-dominated character.
      The condenser aperture diaphragm can be used for modulations of the image's
      appearance. Specimens can either be illuminated concentrically or obliquely
      (eccentrically) when parts of the illuminating light beams are covered and
      blocked. Moreover, a bright-field-like partial image can be added. In this way,
      the illumination can be optimally adjusted to the specific properties of the
      specimen. The techniques described can lead to improved visual information
      especially in biological specimens consisting of phase structures and additional
      light-absorbing or -reflecting components. Moreover, the specimen's three
      dimensionality can be accentuated with improved clarity because the illuminating
      light beams associated with phase contrast and dark field run to the specimen at
      different angles of incidence.

PMID- 22380759
TI  - Allo-exposure status and leucocyte antibody positivity of blood donors show a
      similar relation with TRALI.
AB  - INTRODUCTION: The fraction of transfusion-related acute lung injury (TRALI) cases
      preventable by deferral of allo-exposed donors has previously been estimated,
      under the assumption this indirectly estimated the contribution of leucocyte
      antibodies to the occurrence of TRALI. Our aim was to estimate the fraction
      preventable by deferral of leucocyte antibody positive donors and to investigate
      the validity of allo-exposure as a marker for leucocyte antibodies. METHODS: All
      donors involved in a series of previously published TRALI patients were tested
      for leucocyte antibodies. The observed number of antibody positive donors was
      compared to the expected number. From this comparison we estimated the
      contribution of leucocyte antibodies to the occurrence of TRALI and compared this
      to the previously reported estimate for allo-exposed donors. RESULTS: Sixty-one
      TRALI patients were included. Of 288 involved donors 43 were expected and 67 were
      observed to be leucocyte antibody positive. The observed percentage of positive
      donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the
      expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be
      preventable by the exclusion of all leucocyte antibody positive donors. For
      plasma-poor products this was 16% (95% CI: -5.0 to 36%). CONCLUSIONS: These
      estimates were similar to those previously published for allo-exposed donors.
      This suggests allo-exposure status can effectively be used in donor deferral
      strategies.

PMID- 22380760
TI  - FINITE ELEMENT ANALYSIS OF PROVISIONAL STRUCTURES OF IMPLANT-SUPPORTED COMPLETE
      PROSTHESES.
AB  - The use of provisional resin implant-supported complete dentures is a fast and
      safe procedure to restore mastication and aesthetics of patients soon after
      surgery and during the adaptation phase to the new denture. This study assessed
      stress distribution of provisional implant-supported fixed dentures and the all
      on-four concept using self-curing acrylic resin (Tempron) and bis-acrylic resin
      (Luxatemp) to simulate functional loads through the 3D finite element method. The
      Solidworks software was used to build 3D models, using acrylic resin (Tempron -
      A) and bis-acrylic resin (Luxatemp - B) for denture captions. Two loading
      patterns were applied on each model: 1) right unilateral axial loading of 150 N
      on the occlusal surfaces of posterior teeth; 2) oblique loading vector of 150 N
      at 45 degrees. The results showed that higher stress was found on the bone crest
      below oblique load application with maximum value of 187.57 MPa on model A and
      167.45 MPa on model B. It was concluded that model B improved stress distribution
      on the denture compared to model A.

PMID- 22380761
TI  - Label-free cell separation using a tunable magnetophoretic repulsion force.
AB  - This paper describes a new label-free cell separation method using a magnetic
      repulsion force resulting from the magnetic susceptibility difference between
      cells and a paramagnetic buffer solution in a microchannel. The difference in the
      magnetic forces acting on different-sized cells is enhanced by adjusting the
      magnetic susceptibility of the surrounding medium, which depends on the
      concentration of paramagnetic salts, such as biocompatible gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA), dissolved therein. As a proof-of
      concept demonstration, Gd-DTPA solutions at concentrations of 0-80 mM were
      applied to separate U937 cells from red blood cells (RBCs) and to distinguish two
      different-sized polystyrene (PS) beads (8 and 10 MUm in diameter). By increasing
      the Gd-DTPA concentration from 0 to 40 mM, the separation resolution of PS beads
      was increased from 0.08 to 0.91. Additionally, we successfully achieved label
      free separation of U937 cells from RBCs with >90% purity and 1 * 10(5) cells/h
      throughput using a 40 mM Gd-DTPA solution.

PMID- 22380762
TI  - Assessment of echocardiographic left atrial size: accuracy of M-mode and two
      dimensional methods and prediction of diastolic dysfunction.
AB  - BACKGROUND: Despite the American Society of Echocardiography recommendation to
      use left atrial volume indexed for body surface area (LAVI) for quantification of
      left atrial size, a variety of methods are used in clinical practice. Our
      objectives were to evaluate the accuracy of M-mode and two-dimensional (2D)
      echocardiographic LA size estimates to LAVI and to determine their ability to
      predict left ventricular diastolic dysfunction. METHODS: In 150 consecutive
      patients, LA diameter (LAD), LA diameter indexed for body surface area (LADI), LA
      area in the apical two- and four-chamber views (LAA 2c and LAA 4c), biplane area
      length LA volume (LAV), and LAVI were obtained. The accuracy of these methods to
      quantify LA enlargement by LAVI, correlation with clinical parameters, and
      ability to act as a surrogate for diastolic dysfunction were determined using
      Pearson correlation coefficients along with univariate and multiple logistic
      analysis. RESULTS: The true degree of LA size (with LAVI as standard) was
      identified by LAD in 45%, LADI in 42%, LAA 4c in 43%, and LAA 2c in 41%. All
      methods showed positive correlation with age, E/E', mitral regurgitation, and
      right atrial size and negative correlation with ejection fraction. LAVI was the
      strongest method to predict any (c = 0.655, P = 0.012) or moderate-severe (P =
      0.856 and P < 0.001) diastolic dysfunction. All methods have greater capacity to
      identify moderate or severe diastolic dysfunction than any degree of diastolic
      dysfunction alone. CONCLUSIONS: One-dimensional and 2D methods inaccurately
      quantify LA size and are inferior to LAVI to predict diastolic dysfunction.

PMID- 22380763
TI  - Calciuria and preeclampsia: a case-control study.
AB  - AIM: Calciuria has been reported to decrease in preeclampsia. We compared
      calciuria among groups of normal, hypertensive and preeclamptic pregnant women,
      and assessed its correlation with the severity of the disease. MATERIAL AND
      METHODS: We conducted a case-control study of mild and severe preeclampsia,
      chronic hypertension, and normal pregnancy, with 14 patients in each group. The
      groups were analyzed by one-way anova (variance analysis) for symmetrical
      distribution and Kruskal-Wallis test for asymmetrical distribution when comparing
      quantitative variables, and by crossed tables when comparing qualitative
      variables. RESULTS: There were statistically significant differences between the
      groups when comparing severe preeclampsia with chronic hypertension, and severe
      preeclampsia with the control group (P < 0.0001). The calciuria medians were 81.5
      mg/24 h for severe preeclampsia, 118 mg/24 h for mild preeclampsia, 226 mg/24 h
      for chronic hypertension, and 272 mg/24 h for the control group. In a ROC
      (receiver operating characteristic) curve analysis, the best cutoff point for
      preeclampsia diagnosis was 167 mg/24 h, with a sensitivity of 75% and a
      specificity of 85%. The outcomes were more severe as the level of calciuria
      dropped. CONCLUSION: Measurement of calciuria can differentiate between severe
      preeclampsia and chronic hypertension, and hypocalciuria is also a marker for
      disease severity.

PMID- 22380765
TI  - Voriconazole and posaconazole improve asthma severity in allergic
      bronchopulmonary aspergillosis and severe asthma with fungal sensitization.
AB  - Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and
      allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal
      lung diseases whose effective treatment remains to be established. Current
      treatment with itraconazole is associated with a 40% failure rate and adverse
      events (AEs). We assessed the effect of voriconazole or posaconazole as second-
      and third-line therapies. Methods. We conducted a retrospective review of adult
      asthmatic patients with either ABPA or SAFS receiving voriconazole or
      posaconazole. Clinical, radiological, and immunological evaluation was used to
      assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5),
      10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or
      developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with
      voriconazole and 9 with posaconazole. Clinical response to voriconazole was
      observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16
      (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for
      posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids
      (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from
      severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%)
      asthmatic patients. There was a marked reduction in OCS and short-acting beta-2
      agonist use, health-care utilization due to asthma, and improvement in overall
      health status. Furthermore, there was a statistically significant reduction in
      immunological markers appearing at 9 months (p = .008) for total IgE and at 12
      months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056).
      Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before
      6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one
      at 3 months and three at 12 months after discontinuation. Conclusion. Both
      voriconazole and posaconazole are potentially effective alternative treatment
      options for SAFS and ABPA and may improve asthma control and reduce severity,
      though larger prospective studies are required to support these retrospective
      study findings.

PMID- 22380767
TI  - Body mass constraints on feeding rates determine the consequences of predator
      loss.
AB  - Understanding effects of species loss in complex food webs with multiple trophic
      levels is complicated by the idiosyncrasy of the predator effects on lower
      trophic levels: direct and indirect effects intermingle and may increase,
      decrease or not affect ecosystem functioning. We introduce a reductionist
      approach explaining a predator's trophic effect only by empirically well-founded
      body-mass constraints on abundance, diet breadth and feeding strength. We
      demonstrate that this mechanistic concept successfully explains the positive,
      negative and neutral net effects of predators on decomposers in a litter
      microcosm experiment. This approach offers a new perspective on the interplay of
      complex interactions within food webs and is easily extendable to include
      phylogenetic and other body-mass independent traits. We anticipate that allometry
      will substantially improve our understanding of idiosyncratic predator effects in
      experiments and the consequences of predator loss in natural ecosystems.

PMID- 22380766
TI  - Design, synthesis, and in vitro activity of novel 2'-O-substituted 15-membered
      azalides.
AB  - Malaria remains one of the most widespread human infectious diseases, and its
      eradication will largely depend on antimalarial drug discovery. Here, we present
      a novel approach to the development of the azalide class of antimalarials by
      describing the design, synthesis, and characterization of novel 2'-O-substituted
      9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives consisting of
      different quinoline moieties covalently liked to a 15-membered azalide scaffold
      at position 2'. By multistep straightforward synthesis, 19 new, stable, and
      soluble compounds were created and biologically profiled. Most active compounds
      from the 4-amino-7-chloroquinoline series showed high selectivity for P.
      falciparum parasites, and in vitro antimalarial activity improved 1000-fold over
      azithromycin. Antimalarial potency was equivalent to chloroquine against the
      sensitive strain (3D7A) and up to 48-fold enhanced over chloroquine against the
      chloroquine-resistant strain (W2). Concurrently, the antibacterial activity of
      the compounds was eliminated, thus facilitating the development of malaria
      specific macrolide agents.

PMID- 22380768
TI  - Cardioprotective effect of transcutaneous electric acupoint stimulation in the
      pediatric cardiac patients: a randomized controlled clinical trial.
AB  - BACKGROUND: Acupuncture pretreatment exerts neuroprotective and cardioprotective
      effects in animal models and in adult patients underwent cardiac surgery;
      however, data in pediatric patient are unavailable. OBJECTIVE/AIM: To investigate
      the effects of transcutaneous electric acupoint stimulation (TEAS) on acute
      myocardial injury from pediatric open-heart surgery. METHODS: Children, aged 2-12
      years, with congenital heart defects scheduled for surgical repair were enrolled.
      They were randomized to TEAS (administrated at bilateral P6 acupoint for 30 min
      after basal anesthesia) and control (an electrode was placed on the arm without
      stimulus) groups. The primary end point was serum cardiac troponin I (cTnI) over
      24 h after aortic unclamping. Furthermore, clinical outcome and serum cytokine
      and C-reactive protein concentrations were evaluated. RESULTS: Seventy eligible
      children were analyzed, 36 in controls and 34 in TEAS group. Compared with
      controls, the mean cTnI levels were significantly lower in TEAS group at 8 h (P =
      0.043) and 24 h (P = 0.046) after aortic unclamping. The duration of ventilation
      (P = 0.004) and length of ICU stay (P = 0.032) was significantly longer in
      controls than in TEAS group. There was a significant difference in the release of
      C-reactive protein at 8 h (P = 0.039) between two groups, whereas the values for
      cytokines were not significant. CONCLUSION: Transcutaneous electric acupoint
      stimulation on the bilateral P6 acupoint is effective for attenuation myocardial
      injury in children undergoing cardiac surgery. The beneficial effects may be
      partially associated with reduction in cTnI and C-reactive protein level in the
      early postoperative period.

PMID- 22380769
TI  - Population PK/PD analysis of metformin using the signal transduction model.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Metformin, a biguanide glucose lowering
      agent, is commonly used to manage type 2 diabetes. The molecular mechanisms of
      metformin have not been fully identified, but turnover of biomarkers such as
      glucose and signalling pathways or translocation of glucose transporters are
      closely related to the glucose-lowering effects of metformin. The PK/PD of
      metformin have been investigated in healthy humans and patients with type 2
      diabetes mellitus and modelling has been performed using an indirect response
      model. WHAT THIS STUDY ADDS: The purpose of this investigation was to develop a
      population PK/PD model for metformin using a signal transduction model in healthy
      humans and predict the PK/PD profile in patients with type 2 diabetes. The aim
      was to compare a previous model (a biophase model) with the signal transduction
      model, and use a more appropriate model to follow the actions of metformin.
      Additionally, our developed model was appropriate to predict the time course of
      plasma metformin and fasting plasma glucose (FPG) concentrations in patients with
      type 2 diabetes. To our knowledge, this is the first published population PK/PD
      analysis using the signal transduction model for metformin. AIMS To develop a
      population pharmacokinetic (PK) and pharmacodynamic (PD) model for metformin (500
      mg) using the signal transduction model in healthy humans and to predict the
      PK/PD profile in patients with type 2 diabetes. METHODS: Following the oral
      administration of 500 mg metformin to healthy humans, plasma concentrations of
      metformin were measured using LC-MS/MS. A sequential modelling approach using
      NONMEM VI was used to facilitate data analysis. Monte Carlo simulation was
      performed to predict the antihyperglycaemic effect in patients with type 2
      diabetes. RESULTS: Forty-two healthy humans were included in the study.
      Population mean estimates (relative standard error, RSE) of apparent clearance,
      apparent volume of distribution and the absorption rate constant were 52.6 l h(
      1) (4.18%), 113 l (56.6%) and 0.41 h(-1) , respectively. Covariate analyses
      revealed that creatinine clearance (CL(CR) ) significantly influenced metformin:
      CL/F= 52.6 * (CL(cr) /106.5)(0.782) . The signal transduction model was applied
      to describe the antihyperglycaemic effect of metformin. The population means for
      efficacy, potency, transit time and the Hill coefficient were estimated to be
      19.8 (3.17%), 3.68 ug ml(-1) (3.89%), 0.5 h (2.89%) and 0.547 (9.05%),
      respectively. The developed model was used to predict the antihyperglycaemic
      effect in patients with type 2 diabetes. The predicted plasma glucose
      concentration value was similar to previous values. CONCLUSIONS: The population
      signal transduction model was developed and evaluated for metformin use in
      healthy volunteers. Model evaluation by non-parametric bootstrap analysis
      suggested that the proposed model was robust and parameter values were estimated
      with good precision.

PMID- 22380770
TI  - Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo
      biloba and their cytotoxic activity.
AB  - Fatty acid synthase (FAS) has been proposed to be a new drug target for the
      development of anticancer agents because of the significant difference in
      expression of FAS between normal and tumour cells. Since a n-hexane-soluble
      extract from Ginkgo biloba was demonstrated to inhibit FAS activity in our
      preliminary test, we isolated active compounds from the n-hexane-soluble extract
      and evaluated their cytotoxic activity in human cancer cells. Three ginkgolic
      acids 1-3 isolated from the n-hexane-soluble extract inhibited the enzyme with
      IC(50) values 17.1, 9.2 and 10.5 uM, respectively, and they showed cytotoxic
      activity against MCF-7 (human breast adenocarcinoma), A549 (human lung
      adenocarcinoma) and HL-60 (human leukaemia) cells. Our findings suggest that
      alkylphenol derivatives might be a new type of FAS inhibitor with cytotoxic
      activity.

PMID- 22380771
TI  - Virtual screening of low molecular weight mushrooms compounds as potential Mdm2
      inhibitors.
AB  - In some human cancer cases, the activity of p53 is inhibited by over-expressed
      Mdm2. The Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and
      subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53
      interaction using small-molecule inhibitors is recognized as a promising strategy
      for anti-cancer drug design. Mushrooms are an important source of powerful
      compounds with anti-tumour properties. In this study, the first virtual screening
      of low molecular weight compounds present in mushroom is presented as potential
      Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the
      virtual screening protocol. The steroids: ganoderic acids X (K(i) = 16nM), Y
      (K(i) = 22nM) and F (K(i) = 69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3beta
      ol (K(i) = 74nM) and polyporenic acid C (K(i) = 59nM) stand out as the top ranked
      potential inhibitors of Mdm2. The docking pose of the most promising compounds
      were carefully analysed and the information provided shows several interesting
      starting points for further development of Mdm2 inhibitors.

PMID- 22380772
TI  - Secondary/tertiary benzenesulfonamides with inhibitory action against the
      cytosolic human carbonic anhydrase isoforms I and II.
AB  - Carbonic anhydrase inhibitors of primary sulfonamide type, RSO(2)NH(2), have
      clinical applications as diuretics, antiglaucoma, antiepileptic, antiobesity and
      antitumor drugs. Here we investigated inhibition of two human cytosolic isozymes,
      hCA I and II, with a series of secondary/tertiary sulfonamides, incorporating
      tosyl moieties (CH(3)C(6)H(4)SO(2)NR1R2). Most compounds inhibited both isoforms
      in low micromolar range, with inhibition constants between 0.181-6.01 MUM against
      hCA I, and 0.209-0.779 MUM against hCA II, respectively. These findings point out
      that substituted benzenesulfonamides may be used as leads for generating
      interesting CAIs probably possessing a distinct mechanism of action compared to
      primary sulfonamides. Indeed, classical RSO(2)NH(2) inhibitors bind in
      deprotonated form to the Zn(II) ion from the CA active site and participate in
      many other favorable interactions with amino acid residues lining the cavity. The
      secondary/tertiary sulfonamides cannot bind to the zinc due to steric hindrance
      and probably are accommodated at the entrance of the active site, in coumarin
      binding-site.

PMID- 22380773
TI  - Identification of aldehyde dehydrogenase 1A1 modulators using virtual screening.
AB  - The highly similar aldehyde dehydrogenase isozymes (ALDH1A1 and ALDH2) have been
      implicated in the metabolism of toxic biogenic aldehydes such as 3,4
      dihydroxyphenylacetaldehyde (DOPAL) and 4-hydroxy-2E-nonenal. We report the down
      regulation of ALDH1A1 mRNA found in substantia nigra tissue of human Parkinson's
      disease (PD) samples using the Genome-Wide SpliceArray(TM) (GWSA(TM)) technology.
      Since DOPAL can rapidly inactivate ALDH1A1 in vitro, we set up a DOPAL-induced
      ALDH1A1 inactivation assay and used this assay to demonstrate that Alda-1, a
      compound originally identified as an activator of ALDH2, can also activate
      ALDH1A1. We carried out a virtual screening of 19,943 compounds and the top 21
      hits from this screen were tested in the DOPAL inactivation assay with ALDH1A1
      which led to identification of an activator as well as two inhibitors among these
      hits. These findings represent an attractive starting point for developing higher
      potency activator compounds that may have utility in restoring the metabolism of
      DOPAL in PD.

PMID- 22380774
TI  - Topoisomerase as target for antibacterial and anticancer drug discovery.
AB  - DNA topoisomerases comprise a major aspect of basic cellular biology and are
      molecular targets for a variety of drugs like antibiotics, antibacterials and
      anticancer drugs. They act by inhibiting the topoisomerase molecule from
      relegating DNA strands after cleavage and convert the topoisomerases molecule
      into a DNA damaging agent. Though drugs of various categories acting through
      different mechanisms are available for the treatment, there are still problems
      associated with the currently available drugs. Therefore, Structural biologists,
      Structural chemists and Medicinal chemists all around the world have been
      identifying, designing, synthesizing and evaluating a variety of novel bioactive
      molecules targeting topoisomerase. This review summarizes types of topoisomerase
      and drug treating each class along with their structural requirement and
      activity. The emphasis has been laid in particular on the new potential
      heterocyles and the possible treatments as well as the current ongoing research
      status in the field of topoisomerase as dual targeting.

PMID- 22380775
TI  - 2-(2-indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design,
      synthesis, biological evaluation and molecular modelling.
AB  - We recently reported that synthetic derivatives of rutaecarpine alkaloid
      exhibited high acetyl cholinesterase (AChE) inhibitory activity and high
      selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel
      effective drugs for the treatment of Alzheimer's disease (AD), in this paper,
      further research results were presented. Starting from a structure-based drug
      design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were
      designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid
      and subjected to pharmacological evaluation as AChE inhibitors. Among them,
      derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high
      selectivity for AChE over BuChE. The structure-activity relationships were
      discussed and their binding conformation and simultaneous interactions mode were
      further clarified by kinetic characterization and the molecular docking studies.

PMID- 22380776
TI  - Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and
      cancer chemopreventive agents.
AB  - A series of novel carbazole chalcones has been synthesised and evaluated for
      radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds
      12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical
      scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of
      oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride).
      Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected
      cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity
      and compounds 12h and 12m have shown good antifungal activity. All the compounds
      were subjected for absorption, distribution, metabolism and excretion (ADME)
      predictions by computational method and found that these molecules could be
      considered as potential candidates for oral drug development.

PMID- 22380777
TI  - Synthesis and HIV-1 RT inhibitory action of novel (4/6-substituted
      benzo[d]thiazol -2-yl)thiazolidin-4-ones. Divergence from the non-competitive
      inhibition mechanism.
AB  - Reverse transcriptase (RT) inhibitors play a major role in the therapy of human
      immunodeficiency virus type 1 (HIV-1) infection. Although, many compounds are
      already used as anti-HIV drugs, research on development of novel inhibitors
      continues, since drug resistant strains appear because of prolonged therapy. In
      this paper, we present the synthesis and evaluation of HIV-1 RT inhibitory action
      of eighteen novel (4/6-halogen/MeO/EtO-substituted benzo[d]thiazol-2
      yl)thiazolidin-4-ones. The two more active compounds (IC50 : 0.04 uM and 0.25 uM)
      exhibited better inhibitory action than the reference compound, nevirapine.
      Docking analysis supports a stable binding of the most active derivative to the
      allosteric centre of RT. Kinetic analysis of two of the most active compounds
      indicate an uncompetitive inhibition mode. This is a desired characteristic,
      since mutations that affect activity of traditional non-competitive NNRTIs may
      not affect activity of compounds of this series. Interestingly, the less active
      derivatives (IC50 > 40 uM) exhibit a competitive mode of action.

PMID- 22380778
TI  - Synthesis and biological properties of C-terminal vinyl ketone pseudotripeptides.
AB  - The ubiquitin-proteasome pathway responsible for the turnover of many cellular
      proteins represents an attractive target in the development of new drug
      therapies: In particular, modulation of the proteasome activity by specific
      inhibitors may represent a useful tool for the treatment of tumours. Here, we
      report synthesis and activity of a new series of oligopseudopeptide analogues
      bearing a vinyl ketone pharmacophoric unit at the C-terminal position. Some
      derivatives showed inhibition in the uM range of the trypsin-like (T-L) active
      site of the proteasome.

PMID- 22380779
TI  - Design, synthesis and preliminary activity evaluation of novel 3-amino-2-hydroxyl
      3-phenylpropanoic acid derivatives as aminopeptidase N/CD13 inhibitors.
AB  - Aminopeptidase N (APN/CD13) over expressed on tumour cells, plays a critical role
      in tumour invasion, metastasis and tumour angiogenesis. In this article, we
      described the design, synthesis and preliminary activity studies of novel 3-amino
      2-hydroxyl-3-phenylpropanoic acid derivatives as APN inhibitors. The in vitro
      enzymatic inhibitions on APN from porcine kidney showed that compound 7e had the
      most potent inhibitory activity against APN with the IC(50) value to 1.26 +/-
      0.01 MUM, which is better than that of bestatin (IC(50) = 2.55 +/- 0.11 MUM). In
      addition, compound 7e also showed better inhibitory activity against APN on human
      ovary clear cell carcinoma cell ES-2 than bestatin with the IC(50) value to 30.19
      +/- 1.02 MUM versus 60.61 +/- 0.1 MUM. Compound 7e could be used as the lead
      compound in the future for anti-cancer agent research.

PMID- 22380780
TI  - Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors.
AB  - This research investigates the synthesis and inhibitory potency of a series of
      novel dipeptidyl allyl sulfones as clan CA cysteine protease inhibitors. The
      structure of the inhibitors consists of a R(1)-Phe-R(2)-AS-Ph scaffold (AS =
      allyl sulfone). R(1) was varied with benzyloxycarbonyl, morpholinocarbonyl, or N
      methylpiperazinocarbonyl substituents. R(2) was varied with either Phe of Hfe
      residues. Synthesis involved preparation of vinyl sulfone analogues followed by
      isomerization to allyl sulfones using n-butyl lithium and t-butyl hydroperoxide.
      Sterics, temperature and base strength were all factors that affected the
      formation and stereochemistry of the allyl sulfone moiety. The inhibitors were
      assayed with three clan CA cysteine proteases (cruzain, cathepsin B and calpain
      I) as well as one serine protease (trypsin). The most potent inhibitor, (E)-Mu
      Phe-Hfe-AS-Ph, displayed at least 10-fold selectivity for cruzain over clan CA
      cysteine proteases cathepsin B and calpain I with a (kobs)/[I] of 6080 +/- 1390
      M(-1)s(-1).

PMID- 22380781
TI  - Design, synthesis and antihypertensive screening of novel pyridazine substituted
      s-triazin-2-imine/one/thione derivatives.
AB  - Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6
      a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of
      reactions starting from appropriate aryl hydrocarbons. The final compounds were
      screened for antihypertensive activities by non-invasive method using Tail Cuff
      method. All the test compounds showed significant antihypertensive activity; 7
      (biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine
      (4p) exhibited antihypertensive activity more than the reference standard drugs.

PMID- 22380782
TI  - Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine - synthesis,
      cytostatic, antiviral and antioxidative studies.
AB  - A series of novel 1,4-substituted semicarbazides 5a-g with a primaquine moiety
      bridged by a carbonyl group at position 1 and a cycloalkyl, aryl, benzyloxy or
      hydroxy substituent at position 4 were prepared and biologically evaluated. The
      synthetic pathways applied for preparation of the title compounds involved
      benzotriazole as synthetic auxiliary. Primaquine semicarbazides 5a-g and their
      synthetic precursors benzotriazolecarbonyl semicarbazides 4 were evaluated for
      cytostatic, antiviral and antioxidative activities. All compounds of the series 5
      showed high selectivity towards MCF-7 cells (breast carcinoma) with IC(50) values
      in the low micromolar range and the most active was benzyl derivative 5c (IC(50)
      1 +/- 0.2 uM). The benzhydryl derivative 5e showed significant cytostatic
      activities towards all the tested cell lines (IC(50) 4-18 uM). The same compound
      was the strongest lipoxygenase inhibitor as well (51%). The highest antioxidant
      activity was demonstrated for the hydroxy derivative 5g and benzotriazolecarbonyl
      semicarbazides 4b,c (61.2-68.5%). No antiviral activity was observed against a
      wide variety of DNA and RNA viruses.

PMID- 22380783
TI  - Redox deposition of nanoscale metal oxides on carbon for next-generation
      electrochemical capacitors.
AB  - Transition metal oxides that mix electronic and ionic conductivity are essential
      active components of many electrochemical charge-storage devices, ranging from
      primary alkaline cells to more advanced rechargeable Li-ion batteries. In these
      devices, charge storage occurs via cation-insertion/deinsertion mechanisms in
      conjunction with the reduction/oxidation of metal sites in the oxide. Batteries
      that incorporate such metal oxides are typically designed for high specific
      energy, but not necessarily for high specific power. Electrochemical capacitors
      (ECs), which are typically composed of symmetric high-surface-area carbon
      electrodes that store charge via double-layer capacitance, deliver their energy
      in time scales of seconds, but at much lower specific energy than batteries. The
      fast, reversible faradaic reactions (typically described as "pseudocapacitance")
      of particular nanoscale metal oxides (e.g., ruthenium and manganese oxides)
      provide a strategy for bridging the power/energy performance gap between
      batteries and conventional ECs. These processes enhance charge-storage capacity
      to boost specific energy, while maintaining the few-second timescale of the
      charge-discharge response of carbon-based ECs. In this Account, we describe three
      examples of redox-based deposition of EC-relevant metal oxides (MnO2, FeOx, and
      RuO2) and discuss their potential deployment in next-generation ECs that use
      aqueous electrolytes. To extract the maximum pseudocapacitance functionality of
      metal oxides, one must carefully consider how they are synthesized and
      subsequently integrated into practical electrode structures. Expressing the metal
      oxide in a nanoscale form often enhances electrochemical utilization (maximizing
      specific capacitance) and facilitates high-rate operation for both charge and
      discharge. The "wiring" of the metal oxide, in terms of both electron and ion
      transport, when fabricated into a practical electrode architecture, is also a
      critical design parameter for achieving characteristic EC charge-discharge
      timescales. For example, conductive carbon must often be combined with the poorly
      conductive metal oxides to provide long-range electron pathways through the
      electrode. However, the ad hoc mixing of discrete carbon and oxide powders into
      composite electrodes may not support optimal utilization or rate performance. As
      an alternative, nanoscale metal oxides of interest for ECs can be synthesized
      directly on the surfaces of nanostructured carbons, with the carbon surface
      acting as a sacrificial reductant when exposed to a solution-phase, oxidizing
      precursor of the desired metal oxide (e.g., MnO4(-) for MnO2). These redox
      deposition methods can be applied to advanced carbon nanoarchitectures with well
      designed pore structures. These architectures promote effective electrolyte
      infiltration and ion transport to the nanoscale metal oxide domains within the
      electrode architecture, which further enhances high-rate operation. 

PMID- 22380784
TI  - Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood
      pressure elevation in spontaneously hypertensive rats by affecting the Akt
      dependent phosphorylation of endothelial nitric oxide synthase.
AB  - Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a
      fundamental regulator of systemic blood pressure. Ginsenosides from  Panax
      ginseng  have been investigated in vitro for the molecular and biochemical
      mechanisms by which they stimulate NO release in vascular endothelial cells;
      however, little research has been done to confirm the physiological relevance of
      these in vitro studies. To address this research gap, the effects of a  P.
      ginseng  extract rich in ginsenosides from protopanaxatriol on spontaneously
      hypertensive rats (SHRs) was examined. Ginseng extract administration stimulated
      nongenomic Akt-mediated eNOS activation, enhanced NO production, improved vessel
      wall thickening, and alleviated hypertension in SHRs, confirming the
      physiological relevance of previous in vitro studies with ginsenosides.

PMID- 22380785
TI  - Marked variation in MSP-119 antibody responses to malaria in western Kenyan
      highlands.
AB  - BACKGROUND: Assessment of malaria endemicity at different altitudes and
      transmission intensities, in the era of dwindling vector densities in the
      highlands, will provide valuable information for malaria control and
      surveillance. Measurement of serum anti-malarial antibodies is a useful marker of
      malaria exposure that indicates long-term transmission potential. We studied the
      serologic evidence of malaria endemicity at two highland sites along a
      transmission intensity cline. An improved understanding of the micro-geographic
      variation in malaria exposure in the highland ecosystems will be relevant in
      planning effective malaria control. METHODS: Total IgG levels to Plasmodium
      falciparum MSP-119 were measured in an age-stratified cohort (< 5, 5-14 and >= 15
      years) in 795 participants from an uphill and valley bottom residents during low
      and high malaria transmission seasons. Antibody prevalence and level was compared
      between different localities. Regression analysis was performed to examine the
      association between antibody prevalence and parasite prevalence. Age-specific MSP
      119 seroprevalence data was fitted to a simple reversible catalytic model to
      investigate the relationship between parasite exposure and age. RESULTS: Higher
      MSP-119 seroprevalence and density were observed in the valley residents than in
      the uphill dwellers. Adults (> 15 years) recorded high and stable immune response
      in spite of changing seasons. Lower responses were observed in children (<= 15
      years), which, fluctuated with changing seasons particularly in the valley
      residents. In the uphill population, annual seroconversion rate (SCR) was 8.3%
      and reversion rate was 3.0%, with seroprevalence reaching a plateau of 73.3% by
      age of 20. Contrary, in the valley bottom population, the annual SCR was 35.8%
      and the annual seroreversion rate was 3.5%, and seroprevalence in the population
      had reached 91.2% by age 10. CONCLUSION: The study reveals the micro-geographic
      variation in malaria endemicity in the highland eco-system; this validates the
      usefulness of sero-epidemiological tools in assessing malaria endemicity in the
      era of decreasing sensitivity of conventional tools.

PMID- 22380787
TI  - Marginal Fit of Implant-supported All-Ceramic Zirconia Frameworks.
AB  - Abstract   Objective: This study evaluated the effect of fabrication techniques
      and cyclic loading on the vertical marginal fit of implant-supported FPD
      frameworks. Methods: Thirty implant supported 3-unit FPD frameworks were
      fabricated on a model system, divided into three equal groups (n=10). The first
      group (control) was constructed from base metal alloy and the other two test
      groups were constructed from All-ceramic Zirconia using CAD/CAM Cerec III system
      and copy milling (Zirconzahn) system.  A cyclic load of 200 N was applied to each
      framework for up to 50,000 cycles. Linear measurements were made in micrometers
      (um) of the vertical gap between the framework and implant-supported abutment at
      16 predetermined points before and after cyclic loading. The frameworks were
      viewed using SEM to inspect any fractographic features. One way analysis of
      variance (ANOVA) was performed to compare the marginal discrepancy values of the
      control and the two test groups and for each group; T-test was applied to
      determine whether significant changes in the fit were observed after cyclic
      loading. (alpha=0.05).  Results: CAD/CAM group showed significantly higher
      marginal gap mean values (80.58 um) than Zirkonzahn and control groups (50.33 um
      and 42.27 um respectively) with no significant difference while, after cyclic
      loading, CAD/CAM group recorded the highest marginal gap mean value (91.50 +/-
      4.260 um) followed by control group (72.00 +/- 2.795 um) while Zirconzahn group
      recorded the lowest marginal gap (65.37 +/- 6.138 um). Cyclic loading
      significantly increased the marginal gap mean values in the control group only.
      Marginal chip was observed in one of the CAD/CAM ceramic frameworks. Conclusions:
      Within the limitations of this study, the fabrication technique influenced the
      marginal fit of the implant supported 3-unit FPD frameworks. Cyclic loading
      failed to change the fit of all-ceramic Zirconia frameworks while; significant
      changes were found in the metal frameworks.

PMID- 22380786
TI  - Integrated approach toward the discovery of glyco-biomarkers of inflammation
      related diseases.
AB  - Glycobiology has contributed tremendously to the discovery and characterization
      of cancer-related biomarkers containing glycans (i.e., glyco-biomarkers) and a
      more detailed understanding of cancer biology. It is now recognized that most
      chronic diseases involve some elements of chronic inflammation; these include
      cancer, Alzheimer's disease, and metabolic syndrome (including consequential
      diabetes mellitus and cardiovascular diseases). By extending the knowledge and
      experience of the glycobiology community regarding cancer biomarker discovery, we
      should be able to contribute to the discovery of diagnostic/prognostic glyco
      biomarkers of other chronic diseases that involve chronic inflammation. Future
      integration of large-scale "omics"-type data (e.g., genomics, epigenomics,
      transcriptomics, proteomics, and glycomics) with computational model building, or
      a systems glycobiology approach, will facilitate such efforts.

PMID- 22380788
TI  - Cold agglutinin syndrome with severe haemolytic anaemia in a patient diagnosed of
      disseminated tuberculosis and concomitant Mycoplasma pneumoniae infection.

PMID- 22380789
TI  - Investigation of the chemical mixing state of individual Asian dust particles by
      the combined use of electron probe X-ray microanalysis and Raman
      microspectrometry.
AB  - In this work, quantitative electron probe X-ray microanalysis (EPMA) and Raman
      microspectrometry (RMS) were applied in combination for the first time to
      characterize the complex internal structure and physicochemical properties of the
      same ensemble of Asian dust particles. The analytical methodology to obtain the
      chemical composition, mixing state, and spatial distribution of chemical species
      within single particles through the combined use of the two techniques is
      described. Asian dust aerosol particles collected in Incheon, Korea, during a
      moderate dust storm event were examined to assess the applicability of the
      methodology to resolve internal mixtures within single particles. Among 92
      individual analyzed particles, EPMA and RMS identified 53% of the particles to be
      internally mixed with two or more chemical species. Information on the spatial
      distribution of chemical compounds within internally mixed individual particles
      can be useful for deciphering the particle aging mechanisms and sources. This
      study demonstrates that the characterization of individual particles, including
      chemical speciation and mixing state analysis, can be performed more in detail
      using EPMA and RMS in combination than with the two single-particle techniques
      alone.

PMID- 22380790
TI  - Mechanisms of disease: the endocrinology of ectopic pregnancy.
AB  - Ectopic pregnancy is defined as a pregnancy implanted outside the uterus, and
      >98% implant in the Fallopian tube. It has a major clinical and socioeconomic
      impact worldwide. The diagnosis of ectopic pregnancy is often difficult and
      resource intensive owing to a lack of accurate biomarkers, and there is a need
      for improved medical management of ectopic pregnancy using new or adjuvant
      treatments. The aetiology of ectopic pregnancy is uncertain, but tubal
      implantation is probably due to retention of the embryo in the Fallopian tube
      owing to impaired embryo-tubal transport and alterations in the tubal
      microenvironment. This comprehensive review of the literature supporting current
      understanding of the endocrinology of Fallopian tube biology and tubal
      implantation focuses on genes expressed in the Fallopian tube regulated by
      oestrogen and progesterone and discusses their potential functions. It concludes
      with a discussion of how advances in this field are enabling the development of
      novel biomarkers and could lead to the identification of potential new treatments
      for ectopic pregnancy.

PMID- 22380791
TI  - Clinical studies of lactoferrin in children.
AB  - Much has been learned in recent years about the mechanisms by which breastfeeding
      improves child health and survival. However, there has been little progress in
      using these insights to improve pediatric care. The aim of this study was to
      review all clinical studies of lactoferrin (LF) in children in an effort to
      determine which interventions may improve pediatric care or require further
      research. We conducted a systematic and critical review of published literature
      and found 19 clinical studies that have used human or bovine LF for different
      outcomes: iron metabolisms and anemia (6 studies), fecal flora (5 studies),
      enteric infections (3 studies), common pediatric illnesses (1 study),
      immunomodulation (3 studies), and neonatal sepsis (1 study). Although the
      efficacies have varied in each trial, the main finding of all published studies
      is the safety of the intervention. Protection against enteric infections and
      neonatal sepsis are the most likely biologically relevant activities of LF in
      children. Future studies on neonatal sepsis should answer critically important
      questions. If the data from these sepsis studies are proven to be correct, it
      will profoundly affect the treatment of low birth weight neonates and will aid in
      the reduction of child mortality worldwide.

PMID- 22380792
TI  - The plant-specific G protein gamma subunit AGG3 influences organ size and shape
      in Arabidopsis thaliana.
AB  - * Control of organ size and shape by cell proliferation and cell expansion is a
      fundamental developmental process, but the mechanisms that set the size and shape
      of determinate organs are largely unknown in plants. * Molecular, genetic,
      cytological and biochemical approaches were used to characterize the roles of the
      Arabidopsis thaliana G protein gamma subunit (AGG3) gene in organ growth. * Here,
      we describe A. thaliana AGG3, which promotes petal growth by increasing the
      period of cell proliferation. Both the N-terminal region and the C-terminal
      domains of AGG3 are necessary for the function of AGG3. By contrast, analysis of
      a series of AGG3 derivatives with deletions in specific domains showed that the
      deletion of any of these domains cannot completely abolish the function of AGG3.
      The GFP-AGG3 fusion protein is localized to the plasma membrane. The predicted
      transmembrane domain plays an important role in the plasma membrane localization
      of AGG3. Genetic analyses revealed that AGG3 action requires a functional G
      protein alpha subunit (GPA1) and G protein beta subunit (AGB1). * Our findings
      demonstrate that AGG3, GPA1 and AGB1 act in the same genetic pathway to influence
      organ size and shape in A. thaliana.

PMID- 22380793
TI  - Contamination of joints with tissue debris and hair after arthrocentesis: the
      effect of needle insertion angle, spinal needle gauge, and insertion of spinal
      needles with and without a stylet.
AB  - OBJECTIVE: To assess fetlock joint contamination with tissue debris and hair
      after arthrocentesis. STUDY DESIGN: Experimental. ANIMALS: Fetlock joint tissues
      (n = 10 horses). METHODS: Soft tissue flaps including the joint capsule were
      dissected from the dorsal fetlock joints of 7 anesthetized horses leaving an
      intact proximal base. Needles inserted through the tissue flaps were flushed into
      tissue cell culture plates and examined for debris. Studies were repeated on
      excised fetlock tissue preparations after being stored for 5 days. Variables
      included gauge and type of needle, insertion of spinal needles with and without a
      stylet, angle of insertion, length of hair, and ante- and postmortem needle
      insertion. Tissue fragments collected from 3 horses were cultured for bacteria.
      RESULTS: Compared to 20 g disposable needles inserted perpendicularly through
      unclipped skin, the odds ratios (ORs) for hair contamination were significantly
      greater for 20 g spinal needles without a stylet, and significantly less for 22 g
      spinal needles inserted with a stylet and for angled insertion of disposable
      needles. Tissue contamination OR was significantly less for 20 g spinal needles
      inserted without a stylet, angled insertion, and clipped hair. Bacteria were
      isolated from 2.6% of tissue fragments. CONCLUSIONS: Angled needle insertion
      reduces joint contamination with tissue and hair. Spinal needles should be
      inserted with a stylet in place and 22 g spinal needles are preferable to 20 g
      spinal needles. Joints may be contaminated with bacteria after routine surgical
      preparation of skin.

PMID- 22380794
TI  - Two-photon fluorescence microscopy imaging of cellular oxidative stress using
      profluorescent nitroxides.
AB  - A range of varying chromophore nitroxide free radicals and their nonradical
      methoxyamine analogues were synthesized and their linear photophysical properties
      examined. The presence of the proximate free radical masks the chromophore's
      usual fluorescence emission, and these species are described as profluorescent.
      Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7
      and 19, respectively) exhibited two-photon absorption (2PA) cross sections of
      approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of
      these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese
      hamster ovary (CHO) cells. Imaging colocalization experiments with the
      commercially available CellROX Deep Red oxidative stress monitor demonstrated
      good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes
      to H(2)O(2)-induced damage was also demonstrated by both one- and two-photon
      fluorescence microscopy. These profluorescent nitroxide probes are potentially
      powerful tools for imaging oxidative stress in biological systems, and they
      essentially "light up" in the presence of certain species generated from
      oxidative stress. The high ratio of the fluorescence quantum yield between the
      profluorescent nitroxide species and their nonradical adducts provides the
      sensitivity required for measuring a range of cellular redox environments.
      Furthermore, their reasonable 2PA cross sections provide for the option of using
      two-photon fluorescence microscopy, which circumvents commonly encountered
      disadvantages associated with one-photon imaging such as photobleaching and poor
      tissue penetration.

PMID- 22380795
TI  - Nanospecific inhibition of pyoverdine siderophore production in Pseudomonas
      chlororaphis O6 by CuO nanoparticles.
AB  - CuO nanoparticles (NPs) exhibit dose-dependent toxicity to bacteria, whereas
      sublethal concentrations of these NPs change bacterial metabolism. Siderophores
      are model metabolites to study the impact of sublethal levels of metallic NPs on
      bacteria because they are involved in survival and interaction with other
      organisms and with metals. We report that a sublethal level of CuO NPs modify the
      production of the fluorescent siderophore pyoverdine (PVD) in a soil beneficial
      bacterium, Pseudomonas chlororaphis O6. The production of PVD was inhibited by
      CuO NPs but not by bulk CuO nor Cu ions at concentrations equivalent to those
      released from the NPs. The cell responses occurred despite the NPs forming near
      micrometer-sized aggregates. The CuO NPs reduced levels of periplasmic and
      secreted PVD and impaired expression from genes encoding proteins involved in PVD
      maturation in the periplasm and export through cell membranes. EDTA restored the
      fluorescence of PVD quenched by Cu ions but did not generate fluorescence with
      cultures of NP-challenged cells, confirming the absence of PVD. Consequently,
      depending on the bacterium, this nanoparticle-specific phenomenon mediating
      cellular reprogramming through effects on secondary metabolism could have an
      impact on critical environmental processes including bacterial pathogenicity.

PMID- 22380796
TI  - Microwave-solvothermal synthesis of various polymorphs of nanostructured TiO2 in
      different alcohol media and their lithium ion storage properties.
AB  - The various polymorphs (anatase, rutile, and brookite) of TiO(2) with different
      nanomorphologies have been synthesized by a facile microwave-assisted
      solvothermal process without surfactants, employing TiCl(4) or TiCl(3) as
      precursors in various alcohol (ethanol, propanol, butanol, and octanol) media.
      The samples have been characterized by X-ray diffraction (XRD), electron
      microscopy, and Brunauer-Emmett-Teller (BET) surface area analysis. The Ti/Cl ion
      concentration, reaction pH, and size of the alcohol molecule are found to control
      the morphology, crystal structure, and crystallite size of the TiO(2) particles.
      Among the various TiO(2) polymorphs synthesized, the rutile TiO(2) spheres built
      up of nanorods that were synthesized with TiCl(4) in octanol have an average pore
      size and surface area of, respectively, 5 nm and 404 m(2)/g and exhibit the best
      electrochemical performance with a capacity of >200 mAh/g after 100 cycles and
      high rate capability. The excellent electrochemical properties originate from the
      nanorod-building morphology and mesoporosity of TiO(2) spheres that provide good
      electrical contact, accommodates the strain smoothly, and facilitates facile
      lithium-ion diffusion.

PMID- 22380798
TI  - High time for change. Further USDA crackdown on soring practices expected.

PMID- 22380799
TI  - Historical perspective on veterinary school accreditation debate.

PMID- 22380800
TI  - What is your diagnosis? Myofibril necrosis with associated vasculitis.

PMID- 22380801
TI  - ECG of the month. Atrial tachycardia.

PMID- 22380802
TI  - Animal behavior case of the month. Motivation for the tail-chasing behavior was
      considered to most likely be multifactorial.

PMID- 22380803
TI  - Pathology in practice. Nonepitheliotropic B-cell lymphoma of the nasal cavity
      with associated suppurative rhinitis and epidermal ulceration and lymphoma of the
      right kidney.

PMID- 22380804
TI  - Pathology in practice. Severe, acute, multifocal, necrohemorrhagic abomasitis
      with marked submucosal and mucosal emphysema and transmural edema with myriad
      surface gram-positive bacilli.

PMID- 22380808
TI  - Clinical evaluation of a single dose of immune plasma for treatment of canine
      parvovirus infection.
AB  - OBJECTIVE: To evaluate the efficacy of administration of a single 12-mL dose of
      canine parvovirus (CPV)-immune plasma for treatment of CPV enteritis. DESIGN:
      Prospective, randomized, double-blinded, placebo-controlled clinical trial.
      ANIMALS: 14 dogs with naturally occurring CPV enteritis. PROCEDURES: Dogs were
      assigned to treatment groups on the basis of randomization tables and were
      administered a single i.v. dose of CPV-immune plasma (treatment group) or an
      equivalent volume of saline (0.9% NaCl) solution (placebo group) within 18 hours
      after admission to the hospital. Treatment and outcome variables evaluated
      included neutrophil, monocyte, and CPV counts; number of days of hospitalization;
      changes in body weight; and cost of treatment. RESULTS: When dogs treated with
      CPV-immune plasma were compared with dogs treated with saline solution, there
      were no significant differences detected among neutrophil or monocyte counts,
      magnitude of viremia, weight change, number of days of hospitalization, or cost
      of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a single 12
      mL dose of immune plasma soon after the onset of CPV enteritis in dogs was not
      effective in ameliorating clinical signs, reducing viremia, or hastening
      hematologic recovery.

PMID- 22380809
TI  - A systematic review of the safety of potassium bromide in dogs.
AB  - OBJECTIVE: To critically evaluate and summarize available information on the
      safety of potassium bromide in dogs. DESIGN: Systematic review. SAMPLE: 111
      references reporting safety information relevant to potassium bromide published
      between 1938 and 2011. PROCEDURES: PubMed searches without date limitations were
      conducted with the terms "potassium bromide" and "sodium bromide" in December
      2009 and October 2011. Additional articles were identified through examination of
      article reference lists and book chapters on seizures in dogs and pharmacology.
      RESULTS: Reversible neurologic signs were the most consistently reported
      toxicoses and were generally associated with adjunctive potassium bromide
      treatment or high serum bromide concentrations. Dermatologic and respiratory
      abnormalities were rare in dogs. Insufficient information was available to assess
      the effects of potassium bromide on behavior or to determine the incidence of
      vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or
      reproductive abnormalities associated with potassium bromide administration.
      Evidence suggested that administration of potassium bromide with food may
      alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid
      hormone abnormalities, and high serum bromide concentrations may be beneficial.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that potassium bromide is
      not an appropriate choice for treatment of every dog with seizures and that
      practitioners should tailor therapeutic regimens and clinical monitoring to each
      dog. Abrupt dietary changes or fluid therapy may compromise seizure control or
      increase the likelihood of adverse events. Availability of an appropriately
      labeled, approved potassium bromide product could provide better assurance for
      veterinarians and their clients of the quality, safety, and effectiveness of the
      product for veterinary use.

PMID- 22380810
TI  - Evaluation of cystoscopic-guided laser ablation of intramural ectopic ureters in
      female dogs.
AB  - OBJECTIVE: To describe and evaluate the short- and long-term outcomes in female
      dogs after cystoscopic-guided laser ablation of ectopic ureters (CLA-EU). DESIGN:
      Prospective case series. ANIMALS: 32 incontinent female dogs with intramural
      ectopic ureters. PROCEDURES: A diagnosis of intramural ectopic ureters was made
      via cystoscopy and fluoroscopy in all patients. Transurethral CLA-EU (via diode
      laser [n = 27] or Holmium:yttrium aluminum garnet laser [3]) was performed to
      relocate the ectopic ureteral orifice cranially into the urinary bladder. All
      vaginal anomalies were treated with the laser concurrently. Follow-up evaluation
      was standardized and included urinary continence scoring, serial bacteriologic
      culture of urine samples, and a follow-up cystoscopy 6 to 8 weeks after CLA-EU.
      RESULTS: Ectopic ureteral orifices of all dogs were initially located in the
      urethra. Eighteen of 30 dogs had bilateral ectopic ureters, and 12 had unilateral
      ectopic ureters. All dogs had other concurrent urinary anomalies. At the time of
      last follow-up (median, 2.7 years after CLA-EU, [range, 12 to 62 months]), 14 of
      30 (47%) dogs did not require any additional treatments following CLA-EU to
      maintain urinary continence. For the 16 residually incontinent dogs, the addition
      of medical management, transurethral bulking-agent injection, or placement of a
      hydraulic occluder was effective in 3, 2, and 4 dogs, respectively, improving the
      overall urinary continence rate to 77% (23/30 dogs). One dog had evidence of
      polypoid cystitis at the neoureteral orifice 6 weeks after CLA-EU that was
      resolved at 3 months. CONCLUSIONS AND CLINICAL RELEVANCE: CLA-EU provided an
      effective, safe, and minimally invasive alternative to surgery for intramural
      ectopic ureters in female dogs.

PMID- 22380811
TI  - Salmonella enterica shedding in hospitalized horses and associations with
      diarrhea occurrence among their stablemates and gastrointestinal-related illness
      or death following discharge.
AB  - OBJECTIVE: To evaluate the potential association between Salmonella enterica
      shedding in hospitalized horses and the risk of diarrhea among stablemates, and
      to characterize gastrointestinal-related illness and death following discharge
      among horses that shed S. enterica while hospitalized. DESIGN: Retrospective
      cohort study [corrected]. ANIMALS: 221 horses (59 that shed S. enterica during
      hospitalization and 162 that tested negative for S. enterica shedding >= 3 times
      during hospitalization). PROCEDURES: Information from medical records
      (signalment, results of microbial culture of fecal samples, clinical status at
      the time of culture, and treatment history) was combined with data collected
      through interviews with horse owners regarding formerly hospitalized horses and
      their stablemates. Data were analyzed to investigate risk factors for death and
      diarrhea. RESULTS: Occurrence of diarrhea among stablemates of formerly
      hospitalized horses was not associated with S. enterica shedding in hospitalized
      horses but was associated with oral treatment with antimicrobials during
      hospitalization. Salmonella enterica shedding during hospitalization was not
      associated with risk of death or gastrointestinal-related illness in study horses
      <= 6 months after discharge, but shedding status and history of gastrointestinal
      illness were associated with increased risk of death during the preinterview
      period. CONCLUSIONS AND CLINICAL RELEVANCE: Stablemates of horses that shed S.
      enterica during hospitalization did not appear to have an increased risk for
      diarrhea, but comingling with horses that receive orally administered
      antimicrobials may affect this risk. Salmonella enterica shedding during
      hospitalization may be a marker of increased long-term risk of death after
      discharge. Risks are likely influenced by the S enterica strain involved and
      biosecurity procedures used.

PMID- 22380812
TI  - Association of clinical signs with endoscopic findings in horses with
      nasopharyngeal cicatrix syndrome: 118 cases (2003-2008).
AB  - OBJECTIVE: To characterize the associations between clinical signs of
      nasopharyngeal cicatrix syndrome (NCS) and endoscopic findings in horses. DESIGN:
      Retrospective, case-control study. ANIMALS: 239 horses (118 case horses and 121
      control horses). PROCEDURES: Medical records of horses that had an endoscopic
      evaluation of the upper airway performed between January 2003 and December 2008
      were reviewed. Clinical signs and the appearance and anatomic locations of
      lesions identified during endoscopic evaluation were reviewed and recorded for
      each horse. The associations between clinical signs and endoscopic findings were
      evaluated by the use of a prospective logistic model that used a Bayesian method
      for inference and was implemented by a Markov chain Monte Carlo method. RESULTS:
      Nasal discharge was associated with acute inflammation of the pharynx and larynx.
      Exercise intolerance was associated with circumferential pharyngeal lesions.
      Respiratory noise was associated with chronic scarring of the pharynx, a
      combination of pharyngeal and laryngeal scarring, and circumferential scarring of
      the pharynx. Respiratory distress was associated with acute inflammation of all
      portions of the airway, especially when there was preexisting scarring and
      narrowing of the airway by >= 50%. Cough did not have any significant association
      with NCS, compared with results in control horses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Associations between the endoscopic appearance of NCS lesions and
      relevant clinical signs will help practitioners identify horses with NCS and
      allow them to select appropriate treatment.

PMID- 22380813
TI  - Exostoses on the palmar or plantar aspect of the diaphysis of the third
      metacarpal or metatarsal bone in horses: 16 cases (2001-2010).
AB  - OBJECTIVE: To characterize the clinical features, diagnostic procedures,
      treatment, and outcome for horses with an exostosis on the palmar or plantar
      cortex of the third metacarpal bone (MC3) or third metatarsal bone (MT3). DESIGN:
      Retrospective case series. ANIMALS: 16 horses. PROCEDURES: Records from 2001
      through 2010 were evaluated to identify horses with radiographic and
      ultrasonographic evidence of an exostosis on an MC3 or MT3. Signalment, history,
      lameness examination results, diagnostic imaging results, surgical and
      histopathologic findings, treatment, and outcome were evaluated. RESULTS: 9
      horses (group A) had unilateral lameness of the exostosis-affected limb that was
      alleviated with local or perineural analgesia. Seven horses (group B) had
      inconsistent lameness of the affected limb. The exostosis was located between the
      middle and distal third of the MC3 or MT3 in all horses. Desmopathy or
      peritendinous fibrosis (or both) of the suspensory ligament at the exostosis site
      was identified in 6 horses. All horses in group A returned to full function after
      conservative or surgical management. Lameness did not recur in any of the horses
      in group B despite no treatment or only conservative management. CONCLUSIONS AND
      CLINICAL RELEVANCE: Exostosis of the palmar cortex of an MC3 or plantar cortex of
      an MT3 should be considered as a cause of lameness in horses. The diagnosis can
      be made by the use of radiography and ultrasonography combined with specific
      diagnostic analgesia. Prognosis for return to athletic activity can be good but
      should be modified contingent on concurrent desmopathy of the suspensory
      ligament.

PMID- 22380814
TI  - Diagnosis and management of hypoaldosteronism without hypoadrenocorticism in an
      alpaca.
AB  - CASE DESCRIPTION: Primary hypoaldosteronism without concurrent
      hypoadrenocorticism was diagnosed in an 8-year-old female alpaca with acute onset
      of weakness progressing to recumbency within 6 hours after onset. CLINICAL
      FINDINGS: Hematologic testing at admission revealed profound hyponatremia,
      hypochloremia, and acidemia with a normal blood potassium concentration. Further
      diagnostic testing, including an ACTH stimulation test, led to a diagnosis of
      hypoaldosteronism in conjunction with normal cortisol production. TREATMENT AND
      OUTCOME: The hembra responded well to i.v. polyionic fluid therapy with sodium
      supplementation and was managed successfully long term with free access to saline
      (0.9% NaCl) solution in addition to water ad libitum. CLINICAL RELEVANCE: To our
      knowledge, this is the first reported case of hypoaldosteronism in an alpaca.
      Hypoaldosteronism should be considered in alpacas as a possible differential
      diagnosis for refractory hyponatremia or for hyponatremia in which an underlying
      etiology is not determined.

PMID- 22380815
TI  - Transversal European survey on testosterone deficiency diagnosis.
AB  - BACKGROUND: Despite being one of the relevant public health threats among ageing
      men, testosterone deficiency syndrome (TDS) is under-recognized and under
      diagnosed. OBJECTIVE: To assess current clinical practices of European physicians
      regarding diagnosis and management of TDS compared with current guidelines.
      METHODS: Postal survey conducted June-November 2008 in France, Germany, Italy and
      Spain among urologists, endocrinologists and general practitioners to collect
      information regarding knowledge of TDS. RESULTS: Among 801 respondents, the
      majority of endocrinologists and urologists had received training on TDS, either
      initially or as part of continuous medical education. TDS was recognized by 86.5%
      of physicians as a true clinical entity, and estimated the prevalence at 10-15%
      of the male population; 73.5% considered that symptoms and a low level of
      testosterone were required for diagnosis. Treatment preferences were quarterly
      intramuscular injections (26.3% of physicians), percutaneous gels (23.9%), matrix
      patch (21.2%), semi-monthly injections (15.4%) and oral therapy (13.4%). Adverse
      effects of testosterone replacement therapy, such as benign prostatic hyperplasia
      and prostate cancer, were a concern for physicians. CONCLUSIONS: TDS management
      appeared to be close to that recommended in international guidelines. Signs and
      symptoms of testosterone deficiency were fairly well known, but some diagnostic
      and treatment variations were observed.

PMID- 22380816
TI  - Vaccine development for patients with cystic fibrosis.

PMID- 22380817
TI  - In light of recent clinical trial results, what lies next for Type 1 diabetes
      vaccine research?

PMID- 22380818
TI  - Computationally optimized antigens to overcome influenza viral diversity.

PMID- 22380820
TI  - Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC
      paradigm.
AB  - The approval of sipuleucel-T has placed cancer vaccines on the verge of becoming
      an effective modality. However, there is much to define to understand the
      intricacies from the multiple confounding factors in vaccine immunotherapy. In
      this article under review, some patients with metastatic cancer who had limited
      tumor burden and minimal prior chemotherapy responded immunologically and
      clinically to PANVAC. This study highlights the need for selecting appropriate
      patient populations for testing of therapeutic vaccines. The rationale of this
      study is that patients with a healthier immune system are capable of responding
      to a vaccine, thus providing long-term tumor control through immune surveillance.

PMID- 22380821
TI  - Issues and challenges in the development of pneumococcal protein vaccines.
AB  - In view of the increasing licensure and use of pneumococcal conjugate vaccines,
      the relatively high cost, and growing issues with serotype emergence, there is a
      need to re-evaluate the role of pneumococcal protein vaccines (PPVs) and pathways
      to their licensure. This paper summarizes the discussion and viewpoints from an
      expert meeting regarding the development of PPVs. A wide spectrum of pneumococcal
      vaccine researchers, developers, and regulators met to review the state of PPVs,
      identify research and development needs, and provide consensus opinions to
      support the introduction of new PPVs where possible. They also discussed clinical
      and regulatory aspects pertinent to these vaccines and generated a series of
      recommendations for moving the field forward.

PMID- 22380822
TI  - Prostate cancer vaccines: moving therapeutic vaccination forward in the post
      Provenge era.
AB  - The focus of extensive research in the area of prostate cancer vaccines has led
      to the approval of the first therapeutic vaccine by the US FDA, sipuleucel-T. As
      our understanding of immunotherapy has increased, novel approaches have been
      investigated that have shown considerable promise. As the field has continued to
      evolve, questions have arisen regarding the potential role of immunotherapy:
      which populations of patients are most likely to benefit from immunotherapy and
      how and when should these therapies be administered? In addition, what are the
      best tools that can be used as surrogates to monitor immune responses to cancer
      vaccines that truly can give meaningful insight toward improving clinical
      outcomes? Finally, how can combination approaches be applied to prostate cancer
      vaccines in terms of both standard of care and experimental therapies? This
      review will address many of these important concepts with regard to prostate
      cancer vaccine therapy.

PMID- 22380823
TI  - A review of the literature on the economics of vaccination against TB.
AB  - The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for
      the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks
      the ability to fully control the TB-endemic and -pandemic situations. The BCG
      vaccine is most effective in preventing pediatric TB, in particular, miliary TB
      and tuberculous meningitis. However, it has a limited effect in preventing
      pulmonary TB, which occurs more frequently in adults. BCG vaccination has now
      been implemented in more than 157 countries worldwide. For various countries, the
      benefits of vaccination are only limited and potentially not cost effective. The
      International Union Against Tuberculosis and Lung Diseases had set the criteria
      for discontinuation of BCG vaccination in 1994. This decision, however, was not
      based on economic considerations. Many developed countries have met the criteria
      set by the International Union Against Tuberculosis and Lung Disease and stopped
      universal BCG vaccination. For developing countries, the BCG vaccine is still an
      effective intervention in protecting young children from TB infection. A lot of
      effort has been spent on R&D of new TB vaccines, the first of which are expected
      to be available within 5-7 years from now. Novel TB vaccines are expected to be
      better and more effective than the current BCG vaccine and should provide a
      viable strategy in controlling TB morbidity and mortality. In this review, the
      aim is to explore economic evaluations that have been carried out for vaccination
      against TB worldwide. In addition to epidemiological evidence, economic evidence
      can play a crucial role in supporting the governments of countries in making
      proper public health decisions on BCG vaccination policies, in particular, to
      implement, continue, or discontinue.

PMID- 22380824
TI  - Immunoprophylaxis and immunotherapy of Staphylococcus epidermidis infections:
      challenges and prospects.
AB  - Previously considered a human commensal, Staphylococcus epidermidis is a frequent
      cause of nosocomial infections and the most common cause of device-related
      infections. Because the expression of toxins and other obvious virulence factors
      is less in S. epidermidis, the biofilm-forming capacity is its major virulence
      factor. Biofilm growth is characterized by high resistance to antimicrobial
      agents and host immune responses, making biofilm eradication tremendously
      difficult. The increasing prevalence of multidrug-resistant S. epidermidis
      strains additionally hampers antimicrobial therapy. Therefore, immunoprophylaxis
      and immunotherapy targeting factors expressed at some point in biofilm formation
      might offer new tools to combat S. epidermidis infections. So far, a limited
      number of targets have been examined for their immunotherapeutic potential. In
      this review, we focus on the already tested and possible targets for vaccine
      development, discuss the accompanying challenges and speculate on future
      possibilities with respect to immunotherapeutic solutions to deal with S.
      epidermidis infections.

PMID- 22380825
TI  - Potential utility of GB virus type C as a preventive vaccine for HIV-1.
AB  - Recent flurries of literature on the beneficial effects of GB virus type C (GBV
      C), a hepatitis C-related virus, in HIV-1 coinfected individuals have raised the
      possibility of its potential use as a preventive vaccine in people with a high
      risk for HIV-1. However, these findings are still controversial, and the
      mechanisms contributing to the apparent beneficial effects of GBV-C are still
      unresolved. Researchers debate whether the beneficial effects of coinfection of
      GBV-C in HIV-1-infected individuals are due to GBV-C viremia or rather the
      presence of GBV-C anti-E2 antibodies. We review the strengths and weaknesses of
      various aspects of the GBV-C debate and propose a new perspective involving
      intracellular molecular events that attempts to synthesize numerous contrasting
      perspectives and ideas, while suggesting new directions for future research in
      this area.

PMID- 22380826
TI  - Development and evaluation of AS03, an Adjuvant System containing alpha
      tocopherol and squalene in an oil-in-water emulsion.
AB  - AS03 is an Adjuvant System composed of alpha-tocopherol, squalene and polysorbate
      80 in an oil-in-water emulsion. In various nonclinical and clinical studies, high
      levels of antigen-specific antibodies were obtained after administration of an
      AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been
      shown to enhance the vaccine antigen-specific adaptive response by activating the
      innate immune system locally and by increasing antigen uptake and presentation in
      draining lymph nodes, a process that is modulated by the presence of alpha
      tocopherol in AS03. In nonclinical models of the AS03-adjuvanted prepandemic H5N1
      influenza vaccine, increased levels of anti-influenza antibody afforded
      protection against disease and against virus replication of influenza strains
      homologous and heterologous to the vaccine strain. By incorporating AS03 in the
      pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with
      nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was
      demonstrated in several assessments in multiple populations. Altogether, the
      nonclinical and clinical data illustrate the ability of AS03 to induce superior
      adaptive responses against the vaccine antigen, principally in terms of antibody
      levels and immune memory. In general, these results support the concept of
      Adjuvant Systems as a plausible approach to develop new effective vaccines.

PMID- 22380833
TI  - [Annular purpuric erythemata on the legs].

PMID- 22380835
TI  - Commentary on C. Garbe et al.: "Histopathological diagnostics of malignant
      melanomas in accordance with the AJCC classification 2009: Revision of the
      literature and recommendations for general practice".

PMID- 22380827
TI  - Novel vaccine development strategies for inducing mucosal immunity.
AB  - To develop protective immune responses against mucosal pathogens, the delivery
      route and adjuvants for vaccination are important. The host, however, strives to
      maintain mucosal homeostasis by responding to mucosal antigens with tolerance,
      instead of immune activation. Thus, induction of mucosal immunity through
      vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or
      other special delivery systems are often used, especially in the elderly. By
      taking advantage of the common mucosal immune system, the targeting of mucosal
      dendritic cells and microfold epithelial cells may facilitate the induction of
      effective mucosal immunity. Thus, novel routes of immunization and antigen
      delivery systems also show great potential for the development of effective and
      safe mucosal vaccines against various pathogens. The purpose of this review is to
      introduce several recent approaches to induce mucosal immunity to vaccines, with
      an emphasis on mucosal tissue targeting, new immunization routes and delivery
      systems. Defining the mechanisms of mucosal vaccines is as important as their
      efficacy and safety, and in this article, examples of recent approaches, which
      will likely accelerate progress in mucosal vaccine development, are discussed.

PMID- 22380836
TI  - How to determine mitotic activity?

PMID- 22380838
TI  - The use of stress analysis methods to evaluate the biomechanics of oral
      rehabilitation with implants.
AB  - Abstract   Because the biomechanical behavior of dental implants is different
      from that of natural tooth, clinical problems may occur. The mechanism of stress
      distribution and load transfer to the implant/bone interface is a critical issue
      affecting the success rate of implants. Therefore, the aim of this study was to
      conduct a brief literature review about the available stress analysis methods to
      study implant-supported prosthesis loading, and to discuss their contributions in
      the biomechanical evaluation of oral rehabilitation with implants. It was found
      that several studies have used experimental, analytical and computational models
      by means of finite element models (FEM), photoelasticity, strain gauges and
      associations of these methods to evaluate the biomechanical behavior of dental
      implants. The FEM has been used to evaluate new components, configurations,
      materials and shape of implants. The greatest advantage of the photoelastic
      method is the ability to visualize the stresses in complex structures such as
      oral structures, and to observe the stress patterns in the whole model, allowing
      to localize and to quantify the stress magnitude. The strain gauges can be used
      to assess in vivo and in vitro stress in prosthesis, implants and teeth. Some
      authors use the strain gauge technique associated with either photoelasticity or
      FEM techniques. These methodologies can be widely applied in Dentistry, mainly in
      the research field. Therefore, they can guide further researches and clinical
      studies by predicting some disadvantages and streamlining the clinical time.

PMID- 22380839
TI  - The critical review of methodologies and approaches to assess the inherent skin
      sensitization potential (skin allergies) of chemicals. Miscellaneous.

PMID- 22380840
TI  - The critical review of methodologies and approaches to assess the inherent skin
      sensitization potential (skin allergies) of chemicals. Part I.
AB  - To critically review currently available methods, or methods under development
      (in vivo, in vitro, in silico, etc.) used in the evaluation of skin sensitization
      potential and their applicability in the derivation of quantitative 'safety
      thresholds'.

PMID- 22380841
TI  - The critical review of methodologies and approaches to assess the inherent skin
      sensitization potential (skin allergies) of chemicals. Part II.
AB  - To identify specific cases, classes or specific use situations of chemicals for
      which 'safety thresholds' or 'safety limits' were set (in regulations, standards,
      in scientific research/clinical work, etc.) and critically review the scientific
      and methodological parameters used to set those limits.

PMID- 22380842
TI  - The critical review of methodologies and approaches to assess the inherent skin
      sensitization potential (skin allergies) of chemicals. Part III.
AB  - For those chemicals identified in point 2 above, to collect and critically
      analyse clinical and statistical evidence on the incidence and morbidity
      (clinical picture) of skin contact allergy (contact dermatitis) cases in the EU
      before (at least 3 years) and after the limits were set, so as to allow an
      assessment of the possible effect of the limits in the reduction/prevention of
      the incidence and morbidity of contact dermatitis.

PMID- 22380843
TI  - Evidence for the different physiological significance of the 6- and 2-minute walk
      tests in multiple sclerosis.
AB  - BACKGROUND: Researchers have recently advocated for the 2-minute walk (2MW) as an
      alternative for the 6-minute walk (6MW) to assess long distance ambulation in
      persons with multiple sclerosis (MS). This recommendation has not been based on
      physiological considerations such as the rate of oxygen consumption (V.O2) over
      the 6MW range. OBJECTIVE: This study examined the pattern of change in V.O2 over
      the range of the 6MW in a large sample of persons with MS who varied as a
      function of disability status. METHOD: Ninety-five persons with clinically
      definite MS underwent a neurological examination for generating an Expanded
      Disability Status Scale (EDSS) score, and then completion of the 6MW protocol
      while wearing a portable metabolic unit and an accelerometer. RESULTS: There was
      a time main effect on V.O2 during the 6MW (p=.0001) such that V.O2 increased
      significantly every 30 seconds over the first 3 minutes of the 6MW, and then
      remained stable over the second 3 minutes of the 6MW. This occurred despite no
      change in cadence across the 6MW (p=.84). CONCLUSIONS: The pattern of change in
      V.O2 indicates that there are different metabolic systems providing energy for
      ambulation during the 6MW in MS subjects and steady state aerobic metabolism is
      reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes
      would represent a test of mixed aerobic and anaerobic work, whereas the second 3
      minutes would represent a test of aerobic work during walking.

PMID- 22380844
TI  - Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen
      dependent cancers.
AB  - Estrogens are involved in the complex regulation of cell proliferation and
      apoptosis of hormone sensitive tumors including breast and endometrial cancers.
      Sulfation is the main pathway for estrogen metabolism, which is believed to be
      involved in the inactivation of estrogens in target tissues. SULT1E1 and PAPSS
      (PAPSS1 and PAPSS2) are responsible for the estrogen sulfation by providing
      catalyzing enzyme and universal sulfate donor. The present study showed the
      expression patterns of SULT1E1 and PAPSS in the breast and endometrial tissues by
      tissue array analysis and the assessment of clinical samples. The estrogen
      sulfation enzymes were comparatively higher in the tumorous tissues than their
      adjacent normal tissues. SULT1E1 overexpression inhibited the tumorigenesis in
      subcutaneous xenograft model. By CCK-8 assay and flow cytometry assay,
      overexpression of SULT1E1 and PAPSS1 by adenovirus blocked the estrogen pro
      proliferating effect and promoted cell apoptosis induced by H(2)O(2) in MCF-7
      cells. By real-time reverse transcription-polymerase chain reaction and western
      blot assays, overexpression of SULT1E1 and PAPSS1 suppressed cell growth and
      triggered apoptosis by downregulating the levels of c-myc, cyclin D1 and bcl-2,
      meanwhile, upregulating bax expression. In conclusion, the discrepancies in
      expressions of SULT1E1 and PAPSS between breast and endometrial tumorous tissues
      and their adjacent normal tissues were prominent. Overexpression of SULT1E1 and
      PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles
      and inducing apoptosis. Thus, targeting SULT1E1 and PAPSS expressions might be an
      important approach for estrogen-dependent cancers.

PMID- 22380845
TI  - Establishment, persistence and effectiveness of arbuscular mycorrhizal fungal
      inoculants in the field revealed using molecular genetic tracing and measurement
      of yield components.
AB  - * Inoculation of crop plants by non-native strains of arbuscular mycorrhizal (AM)
      fungi as bio-enhancers is promoted without clear evidence for symbiotic
      effectiveness and fungal persistence. To address such gaps, the forage legume
      Medicago sativa was inoculated in an agronomic field trial with two isolates of
      Funneliformis mosseae differing in their nuclear rDNA sequences from native
      strains. * The inoculants were traced by PCR with a novel combination of the
      universal fungal NS31 and Glomeromycota-specific LSUGlom1 primers which target
      the nuclear rDNA cistron. The amplicons were classified by restriction fragment
      length polymorphism and sequencing. * The two applied fungal inoculants were
      successfully traced and discriminated from native strains in roots sampled from
      the field up to 2 yr post inoculation. Moreover, field inoculation with inocula
      of non-native isolates of F. mosseae appeared to have stimulated root
      colonization and yield of M. sativa. * Proof of inoculation success and sustained
      positive effects on biomass production and quality of M. sativa crop plants hold
      promise for the role that AM fungal inoculants could play in agriculture.

PMID- 22380846
TI  - Endocytosis and trafficking of human lactoferrin in macrophage-like human THP-1
      cells (1).
AB  - Different cell types have been reported to internalize lactoferrin (Lf) by
      specific or nonspecific receptors. Our studies focused on the endocytic pathway
      of human Lf in macrophage-like THP-1 cells. Lactoferrin was found to be
      internalized by THP-1 cells differentiated with  phorbol myristate acetate.
      Incubation of cells with chlorpromazine and dansylcadaverine, inhibitors of
      clathrin-dependent endocytosis, led to a 50% inhibition of Lf internalization
      compared with untreated cells. Bafilomycin A1 and NH(4)Cl treatment also resulted
      in 40%-60% inhibition, respectively, suggesting that the internalization of Lf
      may partly be mediated by acidic endosome-like organelles. Endocytic uptake of Lf
      was also cholesterol-dependent, as shown by methyl-beta-cyclodextrin or nystatin
      treatment of the cells prior to internalization. Partial colocalization of Lf and
      EEA-1, a marker specific for early endosomes, could be observed. Colocalization
      of Lf with a specific endoplasmic reticulum marker was also detected. Our results
      suggest that Lf is internalized mainly by the clathrin-dependent pathway in THP-1
      cells and targets the ER. The physiological consequences of this intracellular
      trafficking will be the subject of future investigations.

PMID- 22380847
TI  - Isolated right subclavian artery arising from the right pulmonary artery via a
      right-sided ductus arteriosus with associated pulmonary steal phenomenon.
AB  - We present a patient with DiGeorge syndrome and an isolated right subclavian
      artery arising from the right pulmonary artery via a right-sided ductus
      arteriosus. The patient showed a subclavian and pulmonary steal with perfusion of
      the right arm and right lung via retrograde circulation in the right vertebral
      artery. The patient underwent successful surgical repair.

PMID- 22380848
TI  - Hydrothermal synthesis and comparative coordination chemistry of new rare-earth
      V4+ compounds.
AB  - Several new hydrated rare earth vanadates and rare earth oxy-vanadates have been
      synthesized using hydrothermal techniques and characterized using single crystal
      and powder X-ray diffraction and infrared and UV-vis absorption spectroscopies.
      The hydrated rare earth vanadates adopt the space group P2(1)/m with general
      formula A(3)VO(5)(OH)(3) (A = Y (1), Dy (2), or La (3)) and contain anionic
      distorted square pyramidal [VO(5)](-6) units and AO(7) and AO(8) polyhedra. The
      oxy-vanadates with the general formula A(2)O(VO(4)) (A = Y (4), Dy (5; 6), or Yb
      (7)) form two polymorphs in either P2(1)/c or C2/c space groups and contain
      anionic tetrahedral [VO(4)](-4) units and nonvanadium bonded O(2-) anions in
      distorted [OA(4)] tetrahedra. In all cases, the vanadium ion is in the
      tetravalent oxidation state, and its original source was the trace V(4+)
      impurities in YVO(4). The observed vanadyl and equatorial vanadium-oxygen bond
      lengths about the square pyramid in compounds 1-3 and the tetrahedral vanadium
      coordination found in compounds 4-7 are unusual for V(4+). The electronic and
      vibrational spectra are also reported and correlated with the appropriate
      coordination environment.

PMID- 22380849
TI  - TCP transcription factors interact with AS2 in the repression of class-I KNOX
      genes in Arabidopsis thaliana.
AB  - Leaf organogenesis occurs within the peripheral zone of the shoot apical meristem
      (SAM). The initiation and subsequent development of a leaf requires the stable
      repression of a highly conserved class of plant genes, namely class-I KNOTTED 1
      like homeobox (KNOX) genes. In Arabidopsis, this class comprises four members:
      SHOOT MERISTEMLESS (STM); BREVIPEDICELLUS (BP); KNAT2 and KNAT6. Two
      transcription factors, ASYMMETRIC LEAVES 1 (AS1) and AS2, are known to form a
      protein complex to repress BP, KNAT2 and KNAT6. Here, we show that AS2 physically
      interacts with the microRNA319 (miR319)-regulated CINCINNATA-like TEOSINTE
      BRANCHED 1-CYCLOIDEA-PCF (TCP) transcription factors in vitro and in vivo. By
      chromatin immunoprecipitation, we demonstrated that AS2 and TCPs bind to similar
      regions of the BP and KNAT2 promoters. In addition, DNA-binding activities of the
      TCP proteins rely on the presence of AS2, as the activities were dramatically
      reduced in the as2 mutant. The jaw-D mutant, which overexpresses MIR319a to
      downregulate several target TCP genes, strongly enhanced the as2 phenotypes and
      caused more severe ectopic expression of BP, KNAT2 and KNAT6. Our results reveal
      that KNOX repression requires different types of transcription factors that
      function together to ensure normal leaf development.

PMID- 22380850
TI  - The health care burden of patients with epilepsy in the United States: an
      analysis of a nationwide database over 15 years.
AB  - OBJECT: The aim of this study was to analyze the national health care burden of
      patients diagnosed with epilepsy in the US and to analyze any changes in the
      length of stay, mean charges, in-hospital deaths (mortality), and disposition at
      discharge. METHODS: A retrospective review of the Nationwide Inpatient Sample
      (NIS) database for epilepsy admissions was completed for the years from 1993 to
      2008. The NIS is maintained by the Agency for Healthcare Research and Quality and
      represents a 20% random stratified sample of all discharges from nonfederal
      hospitals within the U.S. Patients with epilepsy were identified using ICD-9
      codes beginning with 345.XX. Approximately 1.1 million hospital admissions were
      identified over a span of 15 years. RESULTS: Over this 15-year period (between
      1993 and 2008), the average hospital charge per admission for patients with
      epilepsy has increased significantly (p < 0.001) from $10,050 to $23,909, an
      increase of 137.9%. This is in spite of a 33% decrease in average length of stay
      from 5.9 days to 3.9 days. There has been a decrease in the percentage of in
      hospital deaths by 57.9% and an increase in discharge to outside medical
      institutions. CONCLUSIONS: The total national charges associated with epilepsy in
      2008 were in excess of $2.7 billion (U.S. dollars, normalized). During the
      studied period, the cost per day for patients rose from $1703.39 to $6130.51. In
      spite of this drastic increase in health care cost to the patient, medical and
      surgical treatment for epilepsy has not changed significantly, and epilepsy
      remains a major source of morbidity.

PMID- 22380851
TI  - Long-term outcome of extratemporal resection in posttraumatic epilepsy.
AB  - OBJECT: Posttraumatic epilepsy (PTE) is a common cause of medically intractable
      epilepsy. While much of PTE is extratemporal, little is known about factors
      associated with good outcomes in extratemporal resections in medically
      intractable PTE. The authors investigated and characterized the long-term outcome
      and patient factors associated with outcome in this population. METHODS: A single
      institution retrospective query of all epilepsy surgeries at Regional Epilepsy
      Center at the University of Washington was performed for a 17-year time span with
      search terms indicative of trauma or brain injury. The query was limited to adult
      patients who underwent an extratemporal resection (with or without temporal
      lobectomy), in whom no other cause of epilepsy could be identified, and for whom
      minimum 1-year follow-up data were available. Surgical outcomes (in terms of
      seizure reduction) and clinical data were analyzed and compared. RESULTS: Twenty
      one patients met inclusion and exclusion criteria. In long-term follow-up 6
      patients (28%) were seizure-free and an additional 6 (28%) had a good outcome of
      2 or fewer seizures per year. Another 5 patients (24%) experienced a reduction in
      seizures, while only 4 (19%) did not attain significant benefit. The presence of
      focal encephalomalacia on imaging was associated with good or excellent outcomes
      in 83%. In 8 patients with the combination of encephalomalacia and invasive
      intracranial EEG, 5 (62.5%) were found to be seizure free. Normal MRI
      examinations preoperatively were associated with worse outcomes, particularly
      when combined with multifocal or poorly localized EEG findings. Two patients
      suffered complications but none were life threatening or disabling. CONCLUSIONS:
      Many patients with extratemporal PTE can achieve good to excellent seizure
      control with epilepsy surgery. The risks of complications are acceptably low.
      Patients with focal encephalomalacia on MRI generally do well. Excellent outcomes
      can be achieved when extratemporal resection is guided by intracranial EEG
      electrodes defining the extent of resection.

PMID- 22380852
TI  - Vagus nerve stimulation after lead revision.
AB  - OBJECT: Vagus nerve stimulation (VNS) has demonstrated benefit in patients with
      medically intractable partial epilepsy. As in other therapies with mechanical
      devices, hardware failure occurs, most notably within the VNS lead, requiring
      replacement. However, the spiral-designed lead electrodes wrapped around the
      vagus nerve are often encased in dense scar tissue hampering dissection and
      removal. The objective in this study was to characterize VNS lead failure and
      lead revision surgery and to examine VNS efficacy after placement of a new
      electrode on the previously used segment of vagus nerve. METHODS: The authors
      reviewed all VNS lead revisions performed between October 2001 and August 2011 at
      the University of Iowa Hospitals and Clinics. Twenty-four patients underwent 25
      lead revisions. In all cases, the helical electrodes were removed, and a new lead
      was placed on the previously used segment of vagus nerve. All inpatient and
      outpatient records of the 25 lead revisions were retrospectively reviewed.
      RESULTS: Four cases were second lead revisions, and 21 cases were first lead
      revisions. The average time to any revision was 5 years (range 1.8-11.1 years),
      with essentially no difference between a first and second lead revision. The most
      common reason for a revision was intrinsic lead failure resulting in high
      impedance (64%), and the most common symptom was increased seizure frequency
      (72%). The average duration of surgery for the initial implantation in the 15
      patients whose VNS system was initially implanted at the authors' institution was
      much shorter (94 minutes) than the average duration of lead revision surgery (173
      minutes). However, there was a significant trend toward shorter surgical times as
      more revision surgeries were performed. Sixteen of the 25 cases of lead revision
      were followed up for more than 3 months. In 15 of these 16 cases, the revision
      was as effective as the previous VNS lead. In most of these cases, both the
      severity and frequency of seizures were decreased to levels similar to those
      following the previous implantation procedure. Only 1 complication occurred, and
      there were no postoperative infections. CONCLUSIONS: Lead revision surgery
      involving the placement of a new electrode at the previously used segment of
      vagus nerve is effective at decreasing the seizure burden to an extent similar to
      that obtained following the initial VNS implantation. Even with multiple lead
      revisions, patients can obtain VNS efficacy similar to that following the initial
      lead implantation. There is a learning curve with revision surgery, and overall
      the duration of surgery is longer than for the initial implantation. Note,
      however, that complications and infection are rare.

PMID- 22380853
TI  - Vagal nerve stimulation for the treatment of medically refractory epilepsy: a
      review of the current literature.
AB  - OBJECT: The authors conducted a study to evaluate the published results of vagal
      nerve stimulation (VNS) for medically refractory seizures according to evidence
      based criteria. METHODS: The authors performed a review of available literature
      published between 1980 and 2010. Inclusion criteria for articles included more
      than 10 patients evaluated, average follow-up of 1 or more years, inclusion of
      medically refractory epilepsy, and consistent preoperative surgical evaluation.
      Articles were divided into 4 classes of evidence according to criteria
      established by the American Academy of Neurology. RESULTS: A total of 70
      publications were reviewed, of which 20 were selected for review based on
      inclusion and exclusion criteria. There were 2 articles that provided Class I
      evidence, 7 that met criteria for Class II evidence, and 11 that provided Class
      III evidence. The majority of evidence supports VNS usage in partial epilepsy
      with a seizure reduction of 50% or more in the majority of cases and freedom from
      seizure in 6%-27% of patients who responded to stimulation. High stimulation with
      a gradual increase in VNS stimulation over the first 6 weeks to 3 months
      postoperatively is well supported by Class I and II data. Predictors of positive
      response included absence of bilateral interictal epileptiform activity and
      cortical malformations. CONCLUSIONS: Vagal nerve stimulation is a safe and
      effective alternative for adult and pediatric populations with epilepsy
      refractory to medical and other surgical management.

PMID- 22380854
TI  - Brain stimulation for the treatment of epilepsy.
AB  - The treatment of patients with refractory epilepsy has always been challenging.
      Despite the availability of multiple antiepileptic medications and surgical
      procedures with which to resect seizure foci, there is a subset of epilepsy
      patients for whom little can be done. Currently available treatment options for
      these unfortunate patients include vagus nerve stimulation, the ketogenic diet,
      and electric stimulation, both direct and indirect, of brain nuclei thought to be
      involved in epileptogenesis. Studies of electrical stimulation of the brain in
      epilepsy treatment date back to the early 20th century, beginning with research
      on cerebellar stimulation. The number of potential targets has increased over the
      years to include the hippocampus, subthalamic nucleus, caudate nucleus,
      centromedian nucleus, and anterior nucleus of the thalamus (ANT). Recently the
      results of a large randomized controlled trial, the electrical Stimulation of the
      Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial, were published,
      demonstrating a significant reduction in mean seizure frequency with ANT
      stimulation. Soon after, in 2011, the results of a second randomized, controlled
      trial-the NeuroPace RNS trial-were published. The RNS trial examined closed-loop,
      responsive cortical stimulation of seizure foci in patients with refractory
      partial epilepsy, again finding significant reduction in seizure frequency. In
      the present review, the authors examine the modern history of electrical
      stimulation of the brain for the treatment of epilepsy and discuss the results of
      2 important, recently published trials, the SANTE and RNS trials.

PMID- 22380855
TI  - Comparison of seizure control outcomes and the safety of vagus nerve, thalamic
      deep brain, and responsive neurostimulation: evidence from randomized controlled
      trials.
AB  - Epilepsy is a devastating disease, often refractory to medication and not
      amenable to resective surgery. For patients whose seizures continue despite the
      best medical and surgical therapy, 3 stimulation-based therapies have
      demonstrated positive results in prospective randomized trials: vagus nerve
      stimulation, deep brain stimulation of the thalamic anterior nucleus, and
      responsive neurostimulation. All 3 neuromodulatory therapies offer significant
      reductions in seizure frequency for patients with partial epilepsy. A direct
      comparison of trial results, however, reveals important differences among
      outcomes and surgical risk between devices. The authors review published results
      from these pivotal trials and highlight important differences between the trials
      and devices and their application in clinical use.

PMID- 22380856
TI  - Inequities in access to pediatric epilepsy surgery: a bioethical framework.
AB  - Epilepsy is a common childhood condition associated with a considerable medical
      and psychosocial burden. Children in whom medical treatment fails to reduce
      seizure burden represent an especially vulnerable patient population because
      prolonged, uncontrolled seizures are associated with poor developmental and
      neurocognitive outcomes. Surgical treatment in the form of cortical resection,
      functional disconnection, or neuromodulation may alleviate or significantly
      reduce the disease burden for a subset of these patients. However, there remains
      a dichotomy between the perceived benefits of surgery and the implementation of
      surgical strategies in the management of medically intractable epilepsy. The
      current paper presents an analysis of the bioethical implications of existing
      inequities in access to pediatric epilepsy surgery that result from inconsistent
      referral practices and discrepant evaluation techniques. The authors provide a
      basic bioethical framework composed of 5 primary expectations to inform public,
      institutional, and personal policies toward the provision of epilepsy surgery to
      afflicted children.

PMID- 22380857
TI  - Temporal pole proton preoperative magnetic resonance spectroscopy in patients
      undergoing surgery for mesial temporal sclerosis.
AB  - OBJECT: The purpose of this prospective study was to compare the results of
      proton MR spectroscopy (MRS) in temporal poles in patients with unilateral mesial
      temporal sclerosis (MTS) with the histopathological findings of the resected
      temporal poles. METHODS: A total of 23 patients (14 male and 9 female) with a
      mean age of 25.2 years (range 17-45 years) were included in this study, which was
      conducted over a 4-year period. All patients suffered medically refractory
      epilepsy due to unilateral, MRI-proven MTS, with no other imaging abnormalities.
      All participants underwent preoperative single-voxel proton MRS using a 3-T MRI
      unit. The hippocampi and temporal poles were examined bilaterally. The
      concentrations of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) were
      measured, and the NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were calculated. All
      patients underwent anterior temporal lobectomy and ipsilateral
      amygdalohippocampectomy, and surgical specimens from the temporal poles were sent
      for histopathological examination. Comparisons of the spectroscopic and
      histopathological results of the resected temporal poles were performed. The
      modified Engel classification system was used for evaluating seizure outcome in
      the cohort. RESULTS: The preoperative spectroscopic profiles of the sclerotic
      hippocampi were abnormal in all patients, and the contralateral hippocampus
      showed altered spectroscopic findings in 12 patients (52.2%). Spectroscopy of the
      temporal poles demonstrated severely decreased concentrations of NAA, markedly
      increased concentrations of Cho, and increased concentrations of Cr in the
      temporal pole ipsilateral to the MTS in 15 patients (65.2%). Similarly, the
      NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were severely decreased in the temporal
      pole ipsilateral to the MTS in 16 patients (69.6%). Histopathological examination
      of the resected temporal poles demonstrated ischemic changes in 5 patients
      (21.7%), gliotic changes in 4 (17.4%), demyelinating changes in 3 (13.0%), and
      microdysplastic changes in 1 patient (4.3%). Comparisons of the spectroscopic and
      histopathological findings showed that the sensitivity of proton MRS was 100%,
      its specificity was 80%, its positive predictive value was 87%, and its negative
      predictive value was 100%. The mean follow-up time in this study was 3.4 years.
      At the end of the 2nd postoperative year, 17 patients (73.9%) were in Engel Class
      I, 5 (21.7%) were in Class II, and 1 (4.3%) was in Class III. CONCLUSIONS: Proton
      MRS detected altered ipsilateral temporal pole metabolism in patients with
      unilateral MTS. These metabolic changes were associated with permanent
      histological abnormalities of the temporal pole. This finding demonstrates that
      MTS may be a more diffuse histological process, and exact preoperative knowledge
      of its temporal extent becomes of paramount importance in the selection of the
      best surgical approach in these patients. Further validation of the observations
      is necessary for defining the role of temporal pole proton MRS in cases of
      temporal lobe epilepsy.

PMID- 22380858
TI  - Prediction of neuropsychological outcome after resection of temporal and
      extratemporal seizure foci.
AB  - Resection of seizure foci is an effective treatment for the control of medically
      intractable epilepsy. However, cognitive morbidity can occur as a result of
      surgical intervention. This morbidity is dependent on several factors, including
      location and extent of resection, disease characteristics, patient demographic
      characteristics, and functional status of the tissue to be resected. In this
      review article, the authors provide a summary of the neurocognitive outcomes of
      epilepsy surgery with an emphasis on presurgical predictors of postsurgical
      cognitive decline.

PMID- 22380859
TI  - Epilepsy surgery in tuberous sclerosis: a review.
AB  - Seizures are the initial manifestation of tuberous sclerosis complex (TSC) in 90%
      of individuals. The prevalence of epilepsy in TSC is 80%-90% with a large
      proportion refractory to antiepileptic drugs. A review of the literature of
      epilepsy surgery in TSC demonstrates impressive success rates for seizure-free
      outcomes. These studies describe a number of novel noninvasive methods for
      seizure localization including PET, SPECT, and magnetoencephalography.
      Additionally, there is a subset of patients with TSC with bilateral, multifocal,
      or generalized epileptiform discharges that would have previously been excluded
      from resection. New developments in neuroimaging and invasive monitoring with
      intracranial electrodes are useful methods in identifying an epileptogenic tuber
      in these individuals with refractory epilepsy. The authors offer a survey of the
      literature and description of these methods. Additionally they present an
      illustrative case of ictal SPECT and intracranial electroencephalography used in
      the preoperative evaluation of a 10-year-old girl with intractable seizures and
      TSC. This patient ultimately underwent resection of an epileptogenic region
      within the occipital lobe.

PMID- 22380860
TI  - Surgical techniques for investigating the role of the insula in epilepsy: a
      review.
AB  - Intracranial electroencephalography monitoring of the insula is an important tool
      in the investigation of the insula in medically intractable epilepsy and has been
      shown to be safe and reliable. Several methods of placing electrodes for insular
      coverage have been reported and include open craniotomy as well as stereotactic
      orthogonal and stereotactic anterior and posterior oblique trajectories. The
      authors review each of these techniques with respect to current concepts in
      insular epilepsy.

PMID- 22380861
TI  - The periinsular functional hemispherotomy.
AB  - The surgical treatment of refractory epilepsy has evolved as new innovations have
      been created. Disconnective procedures such as hemispherectomy have evolved.
      Presently, hemispherotomy has replaced hemispherectomy to reduce complication
      rates while maintaining good seizure control. Several disconnective techniques
      have been described including the Rasmussen, vertical, and lateral approaches.
      The lateral approach, or periinsular hemispherectomy, was derived from
      modifications on the functional hemispherectomy and involves removal of the
      temporal lobe mesial structures, exposure of the atrium via the circular sulcus,
      internal capsule transection under the central sulcus, intraventricular
      callosotomy, and frontobasal disconnection. The purpose of this article is to
      describe and illustrate in detail the anatomy and operative technique for
      periinsular hemispherotomy, as well as to discuss the nuances and issues involved
      with this procedure.

PMID- 22380862
TI  - Seizure outcomes and mesial resection volumes following selective
      amygdalohippocampectomy and temporal lobectomy.
AB  - OBJECT: Anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy
      (SelAH) are the preferred surgical approaches for the treatment of medically
      refractory epilepsy involving the nondominant and dominant temporal lobes,
      respectively. Both techniques provide access to mesial structures-with the ATL
      providing a wider surgical corridor than SelAH. Because the extent of mesial
      temporal resection potentially impacts seizure outcome, the authors examined
      mesial resection volumes, seizure outcomes, and neuropsychiatric test scores in
      patients undergoing either ATL or transcortical SelAH at a single institution.
      METHODS: A retrospective study was conducted in 96 patients with medically
      refractory mesial temporal lobe epilepsy. Fifty-one patients who had nondominant
      temporal lobe epilepsy underwent standard ATL, and 45 patients with language
      dominant temporal lobe epilepsy underwent transcortical SelAH. Volumetric MRI
      analysis was used to quantify the mesial resection in both groups. In addition,
      the authors examined seizure outcomes and the change in neuropsychiatric test
      scores. RESULTS: Seizure-free outcome in the entire patient cohort was 94% at a
      mean follow-up of 44 months. There was no significant difference in the seizure
      outcome between the 2 groups. The extent of resection of the mesial structures
      following ATL was slightly higher than for SelAH (98% vs. 91%, p < 0.0001). The
      change in neuropsychiatric test scores largely reflected the side of surgery, but
      overall IQ and memory function did not change significantly in either group.
      CONCLUSIONS: Transcortical SelAH provides adequate access to the mesial
      structures, and allows for a resection that is nearly as extensive as that
      achieved with standard ATL. Seizure outcomes and neuropsychiatric sequelae are
      similar in both procedures.

PMID- 22380863
TI  - Failed epilepsy surgery for mesial temporal lobe sclerosis: a review of the
      pathophysiology.
AB  - OBJECT: The object of the current study was to review the electrophysiology and
      pathological substrate of failed temporal lobe surgery in patients with mesial
      temporal sclerosis. METHODS: A systematic review of the literature was performed
      for the years 1999-2010 to assess the cause of failure and to identify potential
      reoperation candidates. RESULTS: Repeat electroencephalographic evaluation
      documenting ipsilateral temporal lobe onset was the most frequent cause for
      recurrent epileptogenesis, followed by contralateral temporal lobe seizures. Less
      frequently, surgical failures demonstrated an electroencephalogram that was
      compatible with extratemporal localization. The generation of occult or new
      epileptogenic zones as well as residual epileptogenic tissue could explain these
      findings. CONCLUSIONS: The outcome of temporal lobe surgery for epilepsy is
      challenged by a somewhat consistent failure rate. Reoperation results in improved
      seizure control in properly selected patients. A detailed knowledge of the
      pathophysiology is beneficial for the reevaluation of these patients.

PMID- 22380864
TI  - Current concepts in epilepsy surgery.

PMID- 22380865
TI  - Enhanced proliferation and functions of in vitro expanded human hair follicle
      outer root sheath cells by low oxygen tension culture.
AB  - INTRODUCTION: Human hair follicle outer root sheath (hORS) cells are known to
      contain hair follicle stem cells and play an important role in healing large size
      wounds, and thus can serve as the cell source for skin engineering. This study
      investigated the effect of low oxygen tension culture on hORS cell proliferation
      potential and functional maintenance during in vitro expansion. MATERIALS AND
      METHODS: Spared postsurgery scalp tissues were donated by 15 patients aged 20-45
      (13 men and 2 women) and were randomly divided into three groups, and isolated
      hORS cells were combined into three pooled cell samples. They were cultured
      either in 4% O(2) or 21% O(2) and were analyzed for cell proliferation, colony
      forming efficiency (CFE), and their ability in forming engineered skin in vitro.
      RESULTS: The results showed that freshly isolated hORS cells expressed CD200
      (22.88+/-8.76), cytokeratin 15 (CK15) (62.57+/-4.72), CD29 (22.53+/-2.49/strong
      and 29.80+/-4.09/dim), and CD49f (28.07+/-15.76/strong and 49.73+/-5.65/dim).
      When exposed in 4% O(2), hORS cells proliferated significantly faster than the
      cells in 21% O(2) for the first three passages (p<0.05), could better maintain
      cobblestone morphology, respectively, generate 3.63-folds more and 23.26-folds
      more cell yields after one and three passages. Additionally, enhanced CFE with
      significantly higher total and holoclone colony numbers were found in the 4% O(2)
      group than in the 21% O(2) group (p<0.05) for the first three passages along with
      better maintained CK15 expression. Furthermore, hORS cells expanded in 4% O(2)
      could form better epidermal structure of in vitro engineered skin comparing to
      the skin engineered by the control cells. CONCLUSION: The low oxygen culture
      method of hORS cells is simple, low cost, less labor intensive, and less
      biosafety concern, which may potentially be applied in skin engineering and
      clinical application.

PMID- 22380866
TI  - Glabridin protects paraoxonase 1 from linoleic acid hydroperoxide inhibition via
      specific interaction: a fluorescence-quenching study.
AB  - The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and is
      responsible for many of HDL's antiatherogenic properties. We previously showed
      that recombinant PON1 is inhibited by linoleic acid hydroperoxide (LA-OOH)
      present in the lipid fraction of the human carotid plaque (LLE) via oxidation of
      the enzyme's Cys284 thiol. Here we explore the effect of glabridin, an isoflavan
      isolated from licorice root, on preventing LA-OOH's inhibitory effect on rePON1
      using the tryptophan-fluorescence-quenching technique and modeling calculations.
      Glabridin significantly prevented rePON1 inhibition by LLE or oxidized linoleic
      acid (by 22% and 15%, respectively), whereas ascorbic acid and Trolox, strong
      antioxidants, had no effect. Glabridin quenched the intrinsic fluorescence of
      rePON1 in a concentration-dependent manner. Binding parameters and modeling
      calculations demonstrated a major role for hydrophobic forces in the rePON1
      glabridin interaction, indicating that it is not the antioxidant capacity of
      glabridin that protects rePON1 from LA-OOH inhibition, but rather its specific
      interaction with the enzyme.

PMID- 22380867
TI  - Isotretinoin and oral contraceptive use in female acne patients varies by
      physician specialty: analysis of data from the National Ambulatory Medical Care
      Survey.
AB  - OBJECTIVE: To determine whether oral contraceptives (OCPs) are underutilized in
      the treatment of acne in women of reproductive age, how use of OCPs compares with
      use of isotretinoin and whether adequate use and documentation of OCPs is
      occurring with isotretinoin. MATERIAL AND METHODS: The National Ambulatory
      Medical Care Survey (NAMCS) was analyzed over the years 1993-2008 for
      isotretinoin and OCP use in females aged 12-55 with acne. RESULTS: Isotretinoin
      was prescribed more often than OCPs at both first visits (4.7% vs. 3.3%) and
      overall visits (13% vs. 2.6%) for acne. Documentation of OCP or other
      contraceptive use occurred only 4.1% of the time overall in patients treated with
      isotretinoin. Specialties varied in both OCP use for acne and contraceptive use
      with isotretinoin, with ob/gyn specialists most likely to prescribe OCPs and
      isotretinoin and to report contraceptive use in patients using isotretinoin, and
      dermatologists least likely to prescribe OCPs. CONCLUSIONS: The findings of the
      current study indicate that OCPs may be underutilized in women with acne.
      Underreporting of contraceptive use with isotretinoin and variations between
      specialties in OCP and isotretinoin use indicate a potential for education about
      the viability of OCPs in acne treatment and the importance of reporting
      contraceptive use with isotretinoin.

PMID- 22380868
TI  - Recurrent thoracolumbar intervertebral disc extrusion after hemilaminectomy and
      concomitant prophylactic fenestration in 662 chondrodystrophic dogs.
AB  - OBJECTIVES: To determine the prevalence and location of recurrent thoracolumbar
      intervertebral disc extrusion (T-L IVDE) after hemilaminectomy with prophylactic
      fenestration (PF) and to document PF-related complications. STUDY DESIGN:
      Retrospective case series. SAMPLE POPULATION: Chondrodystrophic dogs (n = 793).
      METHODS: In 662 successfully recovered dogs (>1 year follow-up), the prevalence
      of dogs with recurrent T-L IVDE that required a 2nd surgery and dogs with
      clinical signs that improved without surgery was evaluated. Prevalence of second
      disc extrusions (SDEs) within T11-L4 intervertebral discs was compared between PF
      discs and non-PF discs. RESULTS: T-L SDEs were intraoperatively confirmed in 15
      dogs (2.3%), 2-61 months after initial surgery and 66 dogs (10.0%) had signs of T
      L IVDE recurrence that improved without surgery (mean follow-up, 44.7 months). No
      dog had further extrusion at the initial T-L site. SDE occurred at a PF disc (n =
      1), adjacent to PF discs (8), or at distant discs (6). Prevalence of SDE in non
      PF discs was 26.2 times higher than PF discs (95% CI: 3.4, 203.4; P < .001).
      Major PF-related complications included iatrogenic introduction of the disc
      material into the spinal canal (n = 1), and vertebral subluxation/instability (3)
      at 1-88 months postoperatively. CONCLUSION: SDE is more likely to occur at non-PF
      discs than PF discs when PF is performed at spaces predisposed to disc extrusion.
      PF is a safe and effective treatment to prevent SDE in chondrodystrophic dogs.

PMID- 22380869
TI  - Process evaluation of an integrated, multidisciplinary intervention programme for
      hand eczema.
AB  - BACKGROUND. Over the last decade, few randomized controlled trials of high
      methodological quality have been carried out to evaluate the effectiveness of
      interventions for patients with hand eczema. Little to no attention has been paid
      to the feasibility of these interventions. This process evaluation was carried
      out to gain insight in the barriers to and facilitators for implementation of an
      intervention for hand eczema. The aims of this process evaluation were to examine
      the feasibility and the satisfaction of the patients and the professionals with
      the integrated care programme, and the perceived barriers to and facilitators for
      the use of the programme. METHODS: Eligible for this study were patients with
      moderate to severe chronic hand eczema who completed the integrated care
      programme. This programme is an intervention provided by a multidisciplinary
      team, consisting of a dermatologist, a specialized nurse, and a clinical
      occupational physician. Data were collected from the patients and the healthcare
      professionals, by means of semistructured telephone interviews, questionnaires,
      and a patient tracking system. Implementation, satisfaction and expectations were
      investigated. RESULTS: Ninety-three patients completed the integrated care
      programme. Compliance with the integrated care programme was good. The results
      indicate good satisfaction of both patients and healthcare professionals with the
      integrated care programme. However, with regard to the process and feasibility of
      the integrated care programme, there is room for improvement. The clinical
      occupational physician was only involved in a very limited number of cases, the
      protocol was not flexible, and the intervention period was too compact. Most of
      the perceived barriers in the present study are at the organizational level.
      CONCLUSION: Satisfaction with the integrated care programme was high among both
      patients and healthcare professionals. The involvement of the clinical
      occupational physician in the treatment, when indicated, should be optimized.
      With the multidisciplinary approach and good communication as a basis for the
      programme, and a more flexible protocol to avoid unnecessary consultations by the
      healthcare professionals, integrated care could be a useful treatment from a
      process evaluation perspective.

PMID- 22380870
TI  - Chemokine C-C motif receptor 5 and C-C motif ligand 5 promote cancer cell
      migration under hypoxia.
AB  - The chemokine CC motif receptor 5 (CCR5) and its ligands have been reported to be
      associated with cancer progression and metastasis. Although recent researches
      have demonstrated a fundamental role of hypoxia in cancer, the effect of hypoxia
      on the expression and function of CCR5 and its ligands in cancer cells is
      unknown. Here, we investigated the status of CCR5 and its ligands in cancer cells
      under hypoxic conditions. Quantitative polymerase chain reaction, western
      blotting and immunofluorescence staining showed that hypoxia induced a strong
      increase of CCR5 expression. Dual luciferase assay and mRNA stability analysis
      indicated that hypoxia-induced CCR5 mRNA expression relied on both
      transcriptional and posttranscriptional mechanisms. We detected the expression of
      CCR5 ligands and found that chemokine CC motif ligand 5 (CCL5) was induced under
      hypoxia. Recombinant human CCL5 stimulated cell migration rather than cell
      proliferation under hypoxia, and neutralization of CCL5 inhibited hypoxia-induced
      migration of cancer cells. Similarly, overexpression of CCR5 increased cell
      migration, and knockdown of CCR5 attenuated hypoxia-mediated cell migration. We
      further showed that hypoxia-inducible factor-1alpha (HIF-1alpha) was involved in
      CCR5 and CCL5 regulation under hypoxia. HIF-1alpha mRNA levels were highly
      correlated with CCR5 mRNA and CCL5 mRNA levels in clinical samples. CCR5 and CCL5
      were highly expressed in breast cancer lymph nodes metastases. Taken together,
      our data suggest that CCR5-CCL5 interaction promotes cancer cell migration under
      hypoxia.

PMID- 22380871
TI  - Guided Flapless Surgery With Immediate Loading For The High Narrow Ridge Without
      Grafting.
AB  - Abstract   Computer guided implant treatment allows implants and associated
      restorations to be precisely placed at the same procedure directly through the
      gingiva with reduced post-operative complications and surgical time. When bone
      height is adequate but very narrow, the virtual guided sleeve is often placed too
      deeply into the ridge crest interfering with the seating of the surgical
      template. This case report of a patient exhibiting very narrow residual ridges
      due to severe resorption describes a new computer guided procedure using a single
      surgical template maintaining bone height and immediate restoration without a
      mucoperiosteal flap. The success of this technique is the result of innovative
      modifications in the software as well as instrumentation. Modifications include
      planning a different implant length virtually to raise the position of guide
      sleeves, alteration of drilling sequences, modifications of the start drill,
      incorporation of osteotomes, and use of an alternative implant seating mount. The
      combination of these methods allows for deeper site preparation and implant
      seating beyond the default settings, without any crestal bone reduction. These
      modifications not only make the guided concept possible for the entire
      preparation and seating procedures, but also allow for the slight removal of bone
      that would interfere with the implant seating through the surgical template
      without a mucoperiosteal flap. This new approach to computer guided surgery
      maintains prosthetic precision in the fabrication of a provisional restoration
      prior to implantation with minimal delivery adjustments using prefabricated
      conical abutments when placing implants at differing levels into the high narrow
      ridge.

PMID- 22380872
TI  - Ionic-liquid-induced changes in the properties of aqueous zwitterionic surfactant
      solution: solvent and rotational relaxation studies.
AB  - In the recent past, the chameleon-like nature of zwitterionic micelles has been
      utilized for performing electrophilic, nucleophilic, base, and acid catalyzed
      reactions. But the use of simple salts to induce the zwitterionic character
      limits the variation to inorganic cations and anions only. To overcome this
      problem, we have used room temperature ionic liquids (RTILs), which can be
      tailored according to need. More precisely, we have shown the effect of added
      RTILs on the nature of water molecules in the palisade layer of a zwitterionic (N
      hexadecyl-N,N-dimethylammonio-1-propanesulfonate (SB-16)) micelle using solvation
      and rotational relaxation studies of C-153 dye. We have carried out a comparative
      study of changes in the solvent and rotational relaxation parameters of C-153 in
      an aqueous solution of SB-16 upon addition of three different ionic liquids
      (ILs): 1-ethyl-3-methylimidazolium ethyl sulfate [C(2)mim][C(2)SO(4)], 1-ethyl-3
      methylimidazolium n-butyl sulfate [C(2)mim][C(4)SO(4)], and 1-ethyl-3
      methylimidazolium n-hexyl sulfate [C(2)mim][C(6)SO(4)]. It has been observed that
      in the presence of added RTILs the solvation dynamics become faster and the
      change in solvation dynamics is more pronounced in the case of
      [C(2)mim][C(6)SO(4)] compared to that for [C(2)mim][C(4)SO(4)] and
      [C(2)mim][C(2)SO(4)]. This can be accounted for by considering the increased
      water penetration (increased microfluidity) with the addition of ILs. In
      accordance with solvation dynamics results, fluorescence anisotropy studies also
      indicate an increase in microfluidity of the palisade layer of the SB-16 micelle
      with the added RTILs. The average rotational relaxation time in 28 mM SB-16 was
      found to be 1.12 ns. With the addition of 800 mM [C(2)mim][C(2)SO(4)], the
      average rotational relaxation time remains the same (1.12 ns), whereas with the
      addition of 800 mM [C(2)mim][C(6)SO(4)] it decreases to 0.40 ns. This observation
      is in agreement with our earlier report on the microfluidity of SB-16 solution
      with the addition of [C(2)mim][C(2)SO(4)] and [C(2)mim][C(6)SO(4)] (Rao, V. G.;
      Ghatak, C.; Ghosh, S.; Mandal, S.; Sarkar, N. Chem. Phys. Chem. DOI:
      10.1002/cphc.201100866).

PMID- 22380873
TI  - Diabetes susceptibility in ethnic minority groups from Turkey, Vietnam, Sri Lanka
      and Pakistan compared with Norwegians - the association with adiposity is
      strongest for ethnic minority women.
AB  - BACKGROUND: The difference in diabetes susceptibility by ethnic background is
      poorly understood. The aim of this study was to assess the association between
      adiposity and diabetes in four ethnic minority groups compared with Norwegians,
      and take into account confounding by socioeconomic position. METHODS: Data from
      questionnaires, physical examinations and serum samples were analysed for 30-to
      60-year-olds from population-based cross-sectional surveys of Norwegians and four
      immigrant groups, comprising 4110 subjects born in Norway (n = 1871), Turkey (n =
      387), Vietnam (n = 553), Sri Lanka (n = 879) and Pakistan (n = 420). Known and
      screening-detected diabetes cases were identified. The adiposity measures BMI,
      waist circumference and waist-hip ratio (WHR) were categorized into levels of
      adiposity. Gender-specific logistic regression models were applied to estimate
      the risk of diabetes for the ethnic minority groups adjusted for adiposity and
      income-generating work, years of education and body height used as a proxy for
      childhood socioeconomic position. RESULTS: The age standardized diabetes
      prevalence differed significantly between the ethnic groups (women/men):
      Pakistan: 26.4% (95% CI 20.1-32.7)/20.0% (14.9-25.2); Sri Lanka: 22.5% (18.1
      26.9)/20.7% (17.3-24.2), Turkey: 11.9% (7.2-16.7)/12.0% (7.6-16.4), Vietnam: 8.1%
      (5.1-11.2)/10.4% (6.6-14.1) and Norway: 2.7% (1.8-3.7)/6.4% (4.6-8.1). The
      prevalence increased more in the minority groups than in Norwegians with
      increasing levels of BMI, WHR and waist circumference, and most for women. Highly
      significant ethnic differences in the age-standardized prevalence of diabetes
      were found for both genders in all categories of all adiposity measures (p <
      0.001). The Odds Ratio (OR) for diabetes adjusted for age, WHR, body height,
      education and income-generating work with Norwegians as reference was 2.9 (1.30
      6.36) for Turkish, 2.7 (1.29-5.76) for Vietnamese, 8.0 (4.19-15.14) for Sri
      Lankan and 8.3 (4.37-15.58) for Pakistani women. Men from Sri Lanka and Pakistan
      had identical ORs (3.0 (1.80-5.12)). CONCLUSIONS: A high prevalence of diabetes
      was found in 30-to 60-year-olds from ethnic minority groups in Oslo, with those
      from Sri Lanka and Pakistan at highest risk. For all levels of adiposity, a
      higher susceptibility for diabetes was observed for ethnic minority groups
      compared with Norwegians. The association persisted after adjustment for
      socioeconomic position for all minority women and for men from Sri Lanka and
      Pakistan.

PMID- 22380874
TI  - Boxing sparring complicated by an acute subdural haematoma and brainstem
      haemorrhage.
AB  - A professional boxer developed an acute subdural haematoma after boxing sparring.
      Despite timely surgical decompression, he had a poor overall outcome
      predominantly from a delayed brainstem haematoma. Magnetic resonance imaging
      (MRI) was used to elucidate the pathophysiology of the patients' injury and
      clinical condition.

PMID- 22380875
TI  - The evaluation of lifestyle interventions in the Netherlands.
AB  - Current investments in preventive lifestyle interventions are relatively low,
      despite the significant impact of unhealthy behaviour on population health. This
      raises the question of whether the criteria used in reimbursement decisions about
      healthcare interventions put preventive interventions at a disadvantage. In this
      paper, we highlight the decision-making framework used in the Netherlands to
      delineate the basic benefits package. Important criteria in that framework are
      'necessity' and 'cost-effectiveness'. Several normative choices need to be made,
      and these choices can have an important impact on the evaluation of lifestyle
      interventions, especially when making these criteria operational and
      quantifiable. Moreover, the implementation of the decision-making framework may
      prove to be difficult for lifestyle interventions. Improvements of the decision
      making framework in the Netherlands are required to guarantee sound evaluations
      of lifestyle interventions aimed at improving health.

PMID- 22380876
TI  - Heterologous expression of the yeast arsenite efflux system ACR3 improves
      Arabidopsis thaliana tolerance to arsenic stress.
AB  - * Arsenic contamination has a negative impact on crop cultivation and on human
      health. As yet, no proteins have been identified in plants that mediate the
      extrusion of arsenic. Here, we heterologously expressed the yeast (Saccharomyces
      cerevisiae) arsenite efflux transporter ACR3 into Arabidopsis to evaluate how
      this affects plant tolerance and tissue arsenic contents. * ACR3 was cloned from
      yeast and transformed into wild-type and nip7;1 Arabidopsis. Arsenic tolerance
      was determined at the cellular level using vitality stains in protoplasts, in
      intact seedlings grown on agar plates and in mature plants grown hydroponically.
      Arsenic efflux was measured from protoplasts and from intact plants, and arsenic
      levels were measured in roots and shoots of plants exposed to arsenate. * At the
      cellular level, all transgenic lines showed increased tolerance to arsenite and
      arsenate and a greater capacity for arsenate efflux. With intact plants, three of
      four stably transformed lines showed improved growth, whereas only transgenic
      lines in the wild-type background showed increased efflux of arsenite into the
      external medium. The presence of ACR3 hardly affected tissue arsenic levels, but
      increased arsenic translocation to the shoot. * Heterologous expression of yeast
      ACR3 endows plants with greater arsenic resistance, but does not lower
      significantly arsenic tissue levels.

PMID- 22380877
TI  - Weight-based volume of injection influences cranial to caudal spread of local
      anesthetic solution in ultrasound-guided transversus abdominis plane blocks in
      canine cadavers.
AB  - OBJECTIVE: To determine if the volume of injected local anesthetic solution
      affects cranial to caudal spread when performing ultrasound-guided transversus
      abdominis plane (TAP) blocks in dogs. STUDY DESIGN: Prospective experimental
      study. ANIMALS: Adult Beagle cadavers (n = 20) METHODS: Bilateral TAP blocks
      using ultrasound guidance was performed in 20 Beagle cadavers (mean +/- SD
      weight, 9.3 +/- 1.4 kg) using a 1:1 solution of methylene blue/bupivacaine
      injected at volumes of 0.25, 0.5, 0.75, and 1.0 mL/kg. Cadavers were dissected to
      determine injectate spread within the transversus abdominis fascial plane.
      RESULTS: The transversus abdominis fascial plane was adequately identified by
      ultrasonography, injected, and dissected in 38 beagle hemi-abdominal walls;
      injectate was not identified in 2 hemi-abdominal walls. Dermatomal spread (number
      of ventral nerve roots saturated by injected solution) was volume dependent (P =
      .026, Kruskal Wallis): 2.9 +/- 0.74 nerve roots for 0.25 mL/kg; 3.4 +/- 1.1 for
      0.5 mL/kg; 4.0 +/- 0.67 for 0.75 mL/kg; and 4.2 +/- 1.2 for 1 mL/kg. CONCLUSION:
      In Beagle cadavers, the volume of injected local anesthetic solution
      significantly affects cranial to caudal spread within the TAP during ultrasound
      guided TAP blocks. The volume of local anesthetic injected could potentially be
      used to augment the spread of analgesic coverage for a given surgical procedure
      in dogs.

PMID- 22380878
TI  - Simulation of Escherichia coli O157:H7 behavior in fresh-cut lettuce under
      dynamic temperature conditions during distribution from processing to retail.
AB  - The temperature of packaged lettuce was recorded throughout a retail supply chain
      in Canada during the various stages of storage and shipping from the processor to
      retail. Temperatures were monitored in 27 cases of lettuce destined for three
      stores in three replicate trials conducted during the winter. A dynamic model
      that predicts the effect of temperature on the growth or die-off of Escherichia
      coli O157:H7 in packaged fresh-cut lettuce was applied to simulate the behavior
      of E. coli O157:H7 in the system. Simulations were carried out using
      distributions to account for variation in the temperature parameter and the die
      off coefficient of the dynamic growth/death model. The results indicate that
      there was a predicted overall mean decline in cell numbers of 0.983 log cfu g-1
      and that the extent of cell death was proportional to the total time spent in the
      cold chain. Slight growth was predicted in a few instances when the dynamic
      temperature was above the permissive temperature of 5 degrees C. These results
      suggest that generally there would be little or no growth of E. coli O157:H7 in
      product maintained at the proper temperature in the chain. Moreover, the
      predicted decline in cell numbers at refrigeration temperatures suggests that
      storage at 5 degrees C or below prior to consumption would reduce populations of
      the pathogen in fresh-cut lettuce.

PMID- 22380879
TI  - Comparative expression analysis of two thermostable nuclease genes in
      Staphylococcus aureus.
AB  - Thermonuclease is known as a specific virulence factor in Staphylococcus aureus.
      It is widely used as a genetic marker for detection of S. aureus in various types
      of food. Previous studies have revealed the existence of two functional
      thermostable nucleases encoded by two different genes (nuc1 and nuc2) in S.
      aureus. To identify the expression characteristics of these two genes,
      comparative mRNA analysis of nuc1 and nuc2 was carried out by quantitative real
      time polymerase chain reaction (PCR). Distinct expression patterns were observed
      at different growth stages, and expression was under the control of the sae
      regulatory system in strain RN4220. The maximum level of nuc1 transcripts was at
      the post-exponential growth phase, and expression was notably down-regulated in a
      sae mutant. In contrast, nuc2 transcript levels declined after the early
      exponential phase, and they were slightly up-regulated in the sae mutant.
      Furthermore, unlike the expression of nuc1, which varied in three different S.
      aureus clinical strains, the transcription of nuc2 remained relatively constant.
      The nuc1 transcription level correlated well with thermonuclease activity
      results, which suggests that nuc1 plays a primary role in thermonuclease activity
      in S. aureus. This information will be useful for understanding thermonuclease
      gene function and alterations of regulation for pathogenesis and diagnosis of S.
      aureus.

PMID- 22380880
TI  - Activation of H-H and H-O bonds at phosphorus with diiron complexes bearing
      pyramidal phosphinidene ligands.
AB  - The complex [Fe(2)Cp(2)(MU-PMes*)(MU-CO)(CO)(2)] (Mes* = 2,4,6-C(6)H(2)(t)Bu(3)),
      which in the solid state displays a pyramidal phosphinidene bridge, reacted at
      room temperature with H(2) (ca. 4 atm) to give the known phosphine complex
      [Fe(2)Cp(2)(MU-CO)(2)(CO)(PH(2)Mes*)] as the major product, along with small
      amounts of other byproducts arising from the thermal degradation of the starting
      material, such as the phosphindole complex [Fe(2)Cp(2)(MU
      CO)(2)(CO){PH(CH(2)CMe(2))C(6)H(2)(t)Bu(2)}], the dimer [Fe(2)Cp(2)(CO)(4)], and
      free phosphine PH(2)Mes*. During the course of the reaction, trace amounts of the
      mononuclear phosphide complex [FeCp(CO)(2)(PHMes*)] were also detected, a
      compound later found to be the major product in the carbonylation of the parent
      phosphinidene complex, with this reaction also yielding the dimer
      [Fe(2)Cp(2)(CO)(4)] and the known diphosphene Mes*P?PMes*. The outcome of the
      carbonylation reactions of the title complex could be rationalized by assuming
      the formation of an unstable tetracarbonyl intermediate [Fe(2)Cp(2)(MU
      PMes*)(CO)(4)] (undetected) that would undergo a fast homolytic cleavage of a Fe
      P bond, this being followed by subsequent evolution of the radical species so
      generated through either dimerization or reaction with trace amounts of water
      present in the reaction media. A more rational synthetic procedure for the
      phosphide complex was accomplished through deprotonation of the phosphine
      compound [FeCp(CO)(2)(PH(2)Mes*)](BF(4)) with Na(OH), the latter in turn being
      prepared via oxidation of [Fe(2)Cp(2)(CO)(4)] with [FeCp(2)](BF(4)) in the
      presence of PH(2)Mes*. To account for the hydrogenation of the parent
      phosphinidene complex it was assumed that, in solution, small amounts of an
      isomer displaying a terminal phosphinidene ligand would coexist with the more
      stable bridged form, a proposal supported by density functional theory (DFT)
      calculations of both isomers, with the latter also revealing that the frontier
      orbitals of the terminal isomer (only 5.7 kJ mol(-1) above of the bridged isomer,
      in toluene solution) have the right shapes to interact with the H(2) molecule. In
      contrast to the above behavior, the cyclohexylphosphinidene complex
      [Fe(2)Cp(2)(MU-PCy)(MU-CO)(CO)(2)] failed to react with H(2) under conditions
      comparable to those of its PMes* analogue. Instead, it slowly reacted with HOR (R
      = H, Et) to give the corresponding phosphinous acid (or ethyl phosphinite)
      complexes [Fe(2)Cp(2)(MU-CO)(2)(CO){PH(OR)Mes*}], a behavior not observed for the
      PMes* complex. The presence of BEt(3) increased significantly the rate of the
      above reaction, thus pointing to a pathway initiated with deprotonation of an O-H
      bond of the reagent by the basic P center of the phosphinidene complex, this
      being followed by the nucleophilic attack of the OR(-) anion at the P site of the
      transient cationic phosphide thus formed. The solid-state structure of the cis
      isomer of the ethanol derivative was determined through a single crystal X-ray
      diffraction study (Fe-Fe = 2.5112(8) A, Fe-P = 2.149(1) A).

PMID- 22380881
TI  - Targeted disruption of an orthologue of DOMAINS REARRANGED METHYLASE 2, OsDRM2,
      impairs the growth of rice plants by abnormal DNA methylation.
AB  - Recent methylome analyses of the entire Arabidopsis thaliana genome using various
      mutants have provided detailed information about the DNA methylation pattern and
      its function. However, information about DNA methylation in other plants is
      limited, partly because of the lack of mutants. To study DNA methylation in rice
      (Oryza sativa) we applied homologous recombination-mediated gene targeting to
      generate targeted disruptants of OsDRM2, a rice orthologue of DOMAINS REARRANGED
      METHYLASE 1 and 2 (DRM1/2), which encode DNA methyltransferases responsible for
      de novo and non-CG methylation in Arabidopsis. Whereas Arabidopsis drm1 drm2
      double mutants showed no morphological alterations, targeted disruptants of rice
      OsDRM2 displayed pleiotropic developmental phenotypes in both vegetative and
      reproductive stages, including growth defects, semi-dwarfed stature, reductions
      in tiller number, delayed heading or no heading, abnormal panicle and spikelet
      morphology, and complete sterility. In these osdrm2 disruptants, a 13.9% decrease
      in 5-methylcytosine was observed by HPLC analysis. The CG and non-CG methylation
      levels were reduced in RIRE7/CRR1 retrotransposons, and in 5S rDNA repeats.
      Associated transcriptional activation was detected in RIRE7/CRR1. Furthermore, de
      novo methylation by an RNA-directed DNA methylation (RdDM) process involving
      transgene-derived exogenous small interfering RNA (siRNA) was deficient in osdrm2
      disrupted cells. Impaired growth and abnormal DNA methylation of osdrm2
      disruptants were restored by the complementation of wild-type OsDRM2 cDNA. Our
      results suggest that OsDRM2 is responsible for de novo, CG and non-CG methylation
      in rice genomic sequences, and that DNA methylation regulated by OsDRM2 is
      essential for proper rice development in both vegetative and reproductive stages.

PMID- 22380882
TI  - Antioxidant activity and protective effect of anthocyanin oligomers on H2O2
      triggered G2/M arrest in retinal cells.
AB  - In this study, the free-radical-scavenging properties of anthocyanin oligomers
      for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, alkyl radical, and hydroxyl
      radical were evaluated using electron spin resonance (ESR) spectroscopy. The DPPH
      radical, alkyl radical, and hydroxyl radical scavenging activity of anthocyanin
      oligomers increased in a dose-dependent manner, with the 50% inhibitory
      concentration (IC50) value of 13.0, 14.0, and 448.0 MUg/mL, respectively. The
      inhibitory effect of anthocyanin oligomers on lipid peroxidation was examined
      with ferric thiocyanate (FTC) and thiobarbituric acid (TBA). The inhibitory
      activity of anthocyanin oligomers was found to be comparable to that of vitamin
      E. In addition, anthocyanin oligomers enhanced the activities of superoxide
      dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), glutathione peroxidase
      (GPx, EC 1.11.1.9), and glutathione-S-transferase (GST, EC 2.5.1.18) in ARPE-19
      cells. In addition, anthocyanin oligomers inhibited the H2O2-induced G2/M phase
      arrest in ARPE-19 cells. Taken together, the present results demonstrate that
      anthocyanin oligomers have high antioxidative activity.

PMID- 22380884
TI  - Assessment of dietary exposure to annatto (E160b), nitrites (E249-250), sulphites
      (E220-228) and tartaric acid (E334) in the French population: the second French
      total diet study.
AB  - The results of the assessment of the dietary exposure to annatto, nitrites,
      tartaric acid and sulphites within the framework of the second French total diet
      study (TDS) are reported. These 4 additives were selected from the Bemrah et al.
      study [Bemrah N, Leblanc JC, Volatier JL. 2008. Assessment of dietary exposure in
      the French population to 13 selected food colours, preservatives, antioxidants,
      stabilizers, emulsifiers and sweeteners. Food Addit Contam B. 1(1):2-14] on 13
      food additives which identified a possible health risk for annatto, sulphites and
      nitrites and a lack of data for tartaric acid. Among the composite samples
      selected for the whole TDS, 524 were analysed for additives (a sample was
      analysed for a given additive when it was identified as a major contributor for
      this additive only): 130 for tartaric acid, 135 for nitrites, 59 for annatto and
      200 for sulphites. Estimated concentrations (minimum lower bound to maximum upper
      bound) vary nationally from 0 to 9 mg/kg for annatto, 0 to 420 mg/kg for tartaric
      acid, 0 to 108 mg/kg for sulphites and 0 to 3.4 mg/kg for nitrites. Based on the
      analytical results, the dietary exposure was calculated for adults and children,
      separately, using lower bound and upper bound assumptions. The European ADIs for
      these 4 additives were not exceeded except for the dietary exposure for sulphites
      among 2.9% of the adult population, where the major contributors were alcoholic
      drinks and especially wine under both hypotheses (lower and upper bound).

PMID- 22380883
TI  - Regulation of glioblastoma multiforme stem-like cells by inhibitor of DNA binding
      proteins and oligodendroglial lineage-associated transcription factors.
AB  - Tumor-initiating stem cells (also referred to as cancer stem cells, CSCs) are a
      subpopulation of cancer cells that play unique roles in tumor propagation,
      therapeutic resistance and tumor recurrence. It is increasingly important to
      understand how molecular signaling regulates the self-renewal and differentiation
      of CSCs. Basic helix-loop-helix (bHLH) transcription factors are critical for the
      differentiation of normal stem cells, yet their roles in neoplastic stem cells
      are not well understood. In glioblastoma neurosphere cultures that contain cancer
      stem cells (GBM-CSCs), the bHLH family member inhibitors of DNA binding protein 2
      and 4 (Id2 and Id4) were found to be upregulated during the differentiation of
      GBM-CSCs in response to histone deacetylase inhibitors. In this study, we
      examined the functions of Id2 and Id4 in GBM neurosphere cells and identified Id
      proteins as efficient differentiation regulators of GBM-CSCs. Overexpression of
      Id2 and Id4 promoted the lineage-specific differentiation of GBM neurosphere
      cells as evidenced by the induction of neuronal/astroglial differentiation
      markers Tuj1 and GFAP and the inhibition of the oligodendroglial marker GalC. Id
      protein overexpression also reduced both stem cell marker expression and
      neurosphere formation potential, a biological marker of cancer cell "stemness."
      We further showed that Id2 and Id4 regulated GBM neurosphere differentiation
      through downregulating of another bHLH family member, the oligodendroglial
      lineage-associated transcription factors (Olig) 1 and 2. Our results provide
      evidence for distinct functions of Id proteins in neoplastic stem cells, which
      supports Id proteins and their downstream targets as potential candidates for
      differentiation therapy in CSCs.

PMID- 22380886
TI  - Traditional healers formalised?
AB  - Traditional healers are the first to be called for help when illness strikes the
      majority of South Africans. Their communities have faith in their ability to cure
      or alleviate conditions managed by doctors, and much more. A visit to such
      practitioners' websites (they are up with the latest advertising technology!)
      shows that they promise help with providing more power, love, security or money,
      protection from evil people and spirits, enhancing one's sex life with penis
      enlargement and vagina tightening spells, etc. Contemplating such claims, it is
      easy to be dismissive of traditional healers. But in this issue of the SAMJ
      Nompumelelo Mbatha and colleagues1 argue that the traditional healers' regulatory
      council, promised by an Act of Parliament, should be established, followed by (or
      preferably preceded by) formal recognition by employers of sick certificates
      issued by traditional healers. Can matters be so simply resolved? What does this
      mean for doctors and other formally recognised healthcare professionals, and how
      to respond to such claims and social pressures?

PMID- 22380888
TI  - Consent for children participating in research.

PMID- 22380889
TI  - Management guidelines of common kidney disorders relevant to South Africa.

PMID- 22380890
TI  - Health professionals should be speaking out about the victimisation of doctors in
      Bahrain.

PMID- 22380891
TI  - Side-effect of acetazolamide in prevention of acute mountain sickness.

PMID- 22380892
TI  - Bogus neurosurgeon beats system hands down.
AB  - The Health Professions Council of South Africa (HPCSA)'s top management has
      ordered a probe of all foreign-qualified specialist registrations going back at
      least a decade, and instituted a 'double verification' mechanism for all future
      such applications following a dramatic system failure.

PMID- 22380893
TI  - Medical aid system: change way overdue.
AB  - The South African medical aid system has evolved in such a way (fragmented risk
      pools, legally beholden to prescribed minimum benefits (PMBs), a free-for-all on
      provider tariffs), that there's little wonder it's adversarial and riven with
      antagonism, exploitation and mistrust.

PMID- 22380894
TI  - Answering when opportunity knocks - SATS goes global.
AB  - One local doctor, by grasping random overlapping educational opportunities, has
      become the catalyst for 'Doctors without Borders' (MSF) wanting to adopt the
      South African Triage Scale (SATS) as its standard emergency protocol for resource
      poor countries world-wide.

PMID- 22380895
TI  - Voluntary male medical circumcision.

PMID- 22380896
TI  - The medical proof doesn't get much better than VMMC.

PMID- 22380898
TI  - Circumcision--what's wrong with plastic rings?
AB  - A key issue facing countries that are scaling up circumcision services is the
      technical difficulty, resources used, complications, and time to healing using
      open surgical techniques, the only methods approved by the major external funding
      agency, PEPFAR. The WHO has developed a framework for evaluating new circumcision
      devices, and two promising disposable plastic devices that have been partially
      evaluated are the Shang Ring and the Prepex system. However, given South Africa's
      disastrous experience with the Tara KLamp, healthy scepticism about plastic ring
      devices is justified. The Gomco clamp has been used in children and adults since
      1935 in the USA, but there are no published studies demonstrating its use in
      adults. Cyanoacrylate tissue adhesive, widely used in all areas of medicine, has
      been shown to be superior to sutures in circumcision in terms of safety, ease of
      use, operative time, and cosmetic results. Our experience in Mozambique suggests
      that Gomco clamp circumcision plus tissue adhesive closure meets all the WHO
      criteria for the ideal circumcision technique, and we strongly recommend that
      African researchers conduct clinical trials to compare it with open surgical
      circumcision.

PMID- 22380899
TI  - Sick certificates issued by South African traditional health practitioners:
      current legislation, challenges and the way forward.
AB  - Traditional health practitioners (THPs) play a significant role in South African
      healthcare. However, the Basic Conditions of Employment Act (BCEA) does not
      consider sick notes issued by THPs to be valid. This creates a dilemma for
      employees, whose right to consult a practitioner of their choice is protected by
      the Constitution. We assessed the current legislation and highlight the
      challenges that employees face in selecting a healthcare system of their choice.
      The services of THPs represent an untapped capacity that can complement and
      strengthen healthcare services, especially in the workforce. The BCEA legislative
      technicality, coupled with the delayed establishment of the Interim THP Council,
      does not relieve the employer's burden of 'illegitimate' medical certificates
      issued by THPs. While seen as a dilemma for some employers, others have
      accommodated African cultural beliefs and accept THP-issued sick notes.
      Finalising the Interim THP Council will  allow THP registration and oblige
      employers to honour sick notes issued by THPs. The empowerment of THPs to play a
      meaningful role in healthcare delivery is of national importance.

PMID- 22380900
TI  - Developing anatomical terms in an African language.
AB  - Clinical and technical information imparted in most African languages involves
      inexact terminology and code switching, so it lacks the explanatory power
      characterised by the English language. African languages are absent in the
      tertiary science education environment and forums where African scientists could
      present scientific material in the medium of African languages. This limits the
      development of African languages in the scientific domain. There has recently
      been a trend in several African languages to develop and intellectualise them,
      especially in the field of medical sciences. The ChiShona language is used to
      explore the ability of an African language to develop new terminology, to name
      the vertebral skeleton and describe it scientifically. It uses word compounding
      to demonstrate terminology development. ChiShona has similarities with several
      hundred other Bantu languages in East, Central and Southern Africa. Advancing
      this language can promote similar developments in others, making them more
      explanatory for the lay public and health professionals.

PMID- 22380905
TI  - Healthcare information and the rural primary care doctor.

PMID- 22380906
TI  - The potential impact of a cataract surgery programme on the care of orphans and
      vulnerable children in Swaziland.
AB  - We aimed to evaluate the potential impact of a cataract surgery programme at the
      Good Shepherd Hospital, Siteki, Swaziland, on the care of orphans and vulnerable
      children in Swaziland. We studied consecutive patients aged 50 years and older
      undergoing surgery for age-related cataract who reported having children living
      in their household. Of 131 subjects recruited, 65 (49.6%) were the primary
      caregivers for the child(ren) in their household. Visual acuities measured 2
      weeks after surgery significantly improved. Four weeks after surgery, there was a
      sizable increase in the proportions of subjects who were able to undertake self
      care activities, attend to activities of daily living, undertake income
      generating activities and care for children. Cataract surgery on elderly visually
      impaired patients has the potential to impact positively on the care of orphans
      and vulnerable children.

PMID- 22380907
TI  - The changing trends of childhood poisoning at a tertiary children's hospital in
      South Africa.
AB  - CONTEXT: Information on childhood poisoning in the developing world, including
      South Africa, is scarce, despite its contribution to morbidity and mortality.
      OBJECTIVE: We describe the profile of children with exposures and poisonings
      presenting to Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town,
      South Africa, from 2003 to 2008 and compare the trends of causative agents over
      the past two decades. METHODS: Cases were identified by review of the RCWMCH case
      records. RESULTS: Of the total incidents (N=2 872), paraffin (kerosene) was the
      commonest agent (n=692, 24%) with 124 poisonings including two deaths. Drugs were
      the most common toxin group (n=988, 34%), including 139 single-drug poisonings
      with 5 deaths; 4 associated with traditional medicine use. Household cleaning
      product incidents (n=302, 10%) resulted in 29 single product poisonings with no
      deaths. Pesticide incidents (n=311, 10%) included 6 deaths; 203 (65%) incidents
      were due to organophosphates or carbamates. The suburban distribution of the main
      toxin groups varied. Comparing 1987 and 2008, the number of incidents decreased
      from 1 116 to 447; drug and paraffin incidents decreased respectively (from 673
      to 150 and from 332 to 87), household cleaning products and cosmetics increased
      (21 to69) and pesticide incidents increased (7 to 69). CONCLUSION: Despite a
      decrease in the overall number of incidents over two decades at RCWMCH, paraffin
      and drugs remain the principal agents responsible for paediatric exposures and
      poisonings, with increasing incidents due to household cleaning products and
      pesticides. Identification of these toxin groups coming from specific suburbs
      allows for targeted prevention initiatives.

PMID- 22380908
TI  - Academic hospital accreditation strengthens postgraduate training programmes:
      case study from Universitas Academic Hospital.
AB  - Benefits derived from the Council for Health Services Accreditation South Africa
      (COHSASA) accreditation of the Universitas Academic Hospital (UAH) in
      Bloemfontein are illustrated. Accreditation assessments were performed between
      2001 and 2007, and full compliance with the COHSASA standards for Academic
      Hospitals was achieved. An initiative to develop thoracic surgery in central
      South Africa (SA) was launched by the Department of Cardiothoracic Surgery at
      UAH. The synergistic effects of quality improvements in healthcare provision
      owing to the accreditation process, and the project to increase service provision
      in thoracic surgery in central SA, have led to a qualitative and quantitative
      increase in thoracic surgical service provision. The importance of academic
      hospital accreditation in strengthening postgraduate training programmes is
      shown, and the accreditation process is recommended for all South African
      academic teaching hospitals to support, improve and sustain our training
      platforms.

PMID- 22380909
TI  - False-positive HIV DNA PCR testing of infants: implications in a changing
      epidemic.
AB  - AIM: To examine false-positive HIV DNA polymerase chain reaction (PCR) test
      results in children, and the potential implications for the paediatric HIV
      epidemic in sub-Saharan Africa. METHODS: A review was done of records over a 6
      year period of children less than 18 months old at an HIV treatment site in South
      Africa, to evaluate those with an initial 'false'-positive HIV DNA PCR result,
      but later proven to be HIV-uninfected with HIV DNA PCR and/or quantitative HIV
      RNA PCR tests. We calculated the influence of changing HIV transmission rates on
      predictive values (PV) of HIV DNA PCR tests in a hypothetical population of all
      HIV-exposed infants over a 1-year period. (Positive PV: proportion of individuals
      with a positive test with disease; negative PV: proportion of individuals with
      negative test and no disease). RESULTS: Of 718 children, 40 with an initial
      positive HIV DNA PCR test were subsequently proven to be HIV-uninfected,
      resulting in a positive PV of 94.4%. Most (75%) uninfected children had PMTCT
      interventions and were asymptomatic or mildly symptomatic (77.5%). Calculations
      using a test specificity of 99.4%, as reported previously, show a decrease in
      positive PV using a single-test strategy from 98.6% at 30% HIV transmission rate,
      to 94.8% at 10% transmission, to 62.5% at 1% transmission. Reduction in test
      specificity further decreases positive PV at low transmission rates. CONCLUSION:
      Decreasing mother-to-child HIV transmission rates reduce the positive predictive
      value of a single HIV DNA PCR test result, necessitating adaptations to
      diagnostic algorithms to avoid misdiagnosis and inappropriate treatment,
      especially with early initiation of antiretroviral therapy in asymptomatic
      infants.

PMID- 22380910
TI  - Nurses at risk for occupationally acquired blood-borne virus infection at a South
      African academic hospital.
AB  - AIM: We aimed to ascertain if there had been any improvement in the number of
      nurses being immunised against hepatitis B virus (HBV) infection in a large
      academic hospital in which, 10 years previously, only 30.6% of the nurses were
      immune to infection with the virus, and to ascertain the incidence of infection
      with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in these
      nurses. METHODS: We studied 170 predominantly black nurses. Their blood was
      tested for the presence of active or past HBV infection using appropriate
      immunoassays, HCV infection by chromatographic immunoassays confirmed by
      polymerase chain reaction assays, and HIV using a rapid test confirmed by enzyme
      linked immunosorbent assays. RESULTS: Serum of 89 (52.4%) nurses was positive for
      hepatitis B surface antibody (anti-HBs). Of these nurses 18 said that they had
      not received the vaccine; the serum of 9 of these was positive for anti-hepatitis
      B core antibody (anti-HBc) as well as anti-HBs, indicating natural infection with
      the virus. Of the nurses positive for anti-HBs, 89 were tested for anti-HBc;
      28.2% tested positive for anti-HBc. Three nurses gave dates of immunisation that
      fell outside of their nursing careers; 3 (1.8%) were actively infected with the
      virus; 2 (1.8%) were infected with HCV; 10 nurses (5.9%) were positive for HIV.
      CONCLUSION: Nurses at this academic hospital remain at high risk of work-related
      HBV infection.

PMID- 22380911
TI  - HBV/HIV co-infection: the dynamics of HBV in South African patients with AIDS.
AB  - OBJECTIVE: As sub-Saharan Africa is highly endemic for hepatitis B virus (HBV)
      and human immunodeficiency virus (HIV) infections, and their co-infection
      requires special management, we aimed to assess the serological and molecular
      characteristics of HBV in patients with AIDS. DESIGN: This was a cross-sectional,
      case control study, which enrolled 200 patients with AIDS and 200 HIV-negative
      controls. HBV serology was done in all participants and HCV serology in
      participants with a hepatitis B core antibody (anti-HBc) only serological
      pattern. Nested HBV polymerase chain reaction (PCR) and HBV viral load assays
      were used for HBV molecular detection. RESULTS: Hepatitis B surface antigen
      (HBsAg) prevalence was 3-fold higher while the 'anti-HBc only' pattern was 6-fold
      higher in the AIDS group compared with the controls. Mean HBV viral load was
      significantly higher in HBsAg-positive patients with CD4+ cell counts <100
      cells/MUl than in patients with CD4+ cell counts of 100-200 cells/MUl (p=0.019).
      There were markedly reduced hepatitis B surface antibody (anti-HBs) titres in the
      AIDS group compared with the controls (p=0.002). A significant proportion of AIDS
      patients with an 'anti-HBc only' pattern had CD4+ cell counts <100 cells/MUl
      (p=0.004). Occult HBV prevalence was 3.5% in the AIDS group compared with 1% in
      the controls (p=0.092). When occult HBV infection was taken into consideration,
      the overall HBV prevalence became 10% in the AIDS group and 3% in the control
      group. CONCLUSION: We showed an increased HBV prevalence in patients with AIDS
      and identified a CD4+ cell count <100 cells/MUl as a major risk factor for the
      'anti-HBc only' pattern and increased HBV replication. These data have
      significant public health implications for HBV in developing countries,
      especially in areas where antiretroviral (ARV) guidelines do not cater for
      HBV/HIV co-infection.

PMID- 22380912
TI  - Sharps disposal practices among diabetic patients using insulin.
AB  - Insulin-dependent diabetic patients are not educated on safe sharps disposal
      methods, so leading to unsafe disposal of needles. Appropriate education on the
      correct disposal of sharps should be an integral part of their diabetic
      counseling. Doctors, nurses and pharmacists should all take responsibility for
      educating and reinforcing information about correct sharps disposal methods.
      Patients should be advised to either discard sharps into puncture resistant
      containers placed into their household refuse, or return them in secure
      containers for disposal by the dispensing institutions. Patients should also be
      educated regarding health risks associated with used needles. The South African
      Metabolic and Endocrine (SEMDSA) Guidelines and the South African Standard
      Treatment Guidelines (STG) should also give clear guidance on the safe disposal
      of needles.

PMID- 22380913
TI  - Chromosome 22q11 in a Xhosa schizophrenia population.
AB  - Chromosome 22q11 aberrations substantially increase the risk for developing
      schizophrenia. Although micro-deletions in this region have been extensively
      investigated in different populations across the world, little is known of their
      prevalence in African subjects with schizophrenia. We screened 110 African Xhosa
      speaking participants with schizophrenia for the presence of micro-deletions. As
      further verification for the presence or absence of 22q11 microdeletions, we
      screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from
      a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data
      from molecular and cytogenetic analyses confirmed the absence of 22q11
      microdeletions in the Xhosa schizophrenia samples. Although the absence of
      chromosome 22q11 micro-deletions in this group of patients does not exclude the
      possibility that it may occur in Xhosa schizophrenia patients, we concluded an
      extremely low prevalence. Our findings suggest that unique susceptibility loci
      may be present in this group.

PMID- 22380914
TI  - Assisted reproductive technology in South Africa: first results generated from
      the South African Register of Assisted Reproductive Techniques.
AB  - OBJECTIVE: We present the first report from the South African Register of
      Assisted Reproductive Techniques. METHODS: All assisted reproductive technology
      (ART) centres in South Africa were invited to join the register. Participant
      centres voluntarily submitted information from 2009 on the number of ART cycles,
      embryo transfers, clinical pregnancies, age of female partners or egg donors, and
      use of fertilisation techniques. Data were anonymised, pooled and analysed.
      RESULTS: The 12 participating units conducted a total of 4 512 oocyte aspirations
      and 3 872 embryo transfers in 2009, resulting in 1 303 clinical pregnancies. The
      clinical pregnancy rate (CPR) per aspiration and per embryo transfer was 28.9%
      and 33.6%, respectively. Fertilisation was achieved by intracytoplasmic sperm
      injection in two-thirds of cycles. In most cycles, 1 - 2 embryos or blastocysts
      were transferred. Female age was inversely related to pregnancy rate. CONCLUSION:
      The register achieved a high rate of participation. The reported number of ART
      cycles covers approximately 6% of the estimated ART demand in South Africa. The
      achieved CPRs compare favourably with those reported for other countries.

PMID- 22380915
TI  - Paediatric anticoagulation guidelines.
AB  - Prepared on behalf of the South African Society of Thombosis and Haemostasis. 
      Background. Recent progress has been made in the understanding of venous thrombo
      embolism (VTE) in children and neonates; however, indications for laboratory
      investigations and therapeutic interventions are not well defined.  Method. The
      Southern African Society of Thrombosis and Haemostasis reviewed available
      literature and comprehensive evidence-based guidelines for paediatric
      antithrombotic therapy. A draft document was produced and revised by consensus
      agreement. The guidelines were adjudicated by independent international experts
      to avoid local bias.  Results and conclusion. We present concise, practical
      guidelines for the clinical management and laboratory investigation of VTE in
      children and neonates. Recommendations reflect current best practice which will
      hopefully lead to improved anticoagulation practice in this age group.

PMID- 22380916
TI  - South African dyslipidaemia guideline consensus statement.
AB  - The European Society of Cardiology together with the European Atherosclerosis
      Society published updated dyslipidaemia guidelines in 2011. SA Heart and the
      Lipid and Atherosclerosis Society of Southern Africa officially adopt these
      guidelines. This statement adapts aspects of the guidelines to the South African
      situation. Using the updated Framingham risk charts, interventional strategies
      are based according to the cardiovascular risk score and low-density lipoprotein
      cholesterol (LDL-C) levels. The Framingham risk score refers to the 10-year risk
      of any cardiovascular event, and includes four categories of risk. Treatment
      targets are those of the European guidelines. The LDL-C goal is 1.8 mmol/l for
      the very high-risk group (>30%), 2.5 mmol/l for the high-risk group (15-30%), and
      3 mmol/l for those below 15% risk. Intensive management of dyslipidaemia in South
      Africa will significantly reduce the cardiovascular disease health burden.

PMID- 22380917
TI  - Mini-slings--concern regarding marketing of these devices in South Africa.

PMID- 22380918
TI  - B,B-Diporphyrinbenzyloxy-BODIPY dyes: synthesis and antenna effect.
AB  - B,B-Diporphyrinbenzyloxy-BODIPY derivatives have been prepared in high yields,
      and the photophysical properties are reported. Singlet energy transfers from
      BODIPY to the porphyrin units have been analyzed.

PMID- 22380919
TI  - Dynamics of solvation and rotational relaxation of coumarin 480 in pure aqueous
      AOT reverse micelle and reverse micelle containing different-sized silver
      nanoparticles inside its core: a comparative study.
AB  - In this work, we have synthesized different-sized silver nanoparticles in an
      aqueous-AOT reverse micellar system under the same condition by choosing
      different reduction processes. We chose two different reducing agents, glucose
      (mild) and sodium borohydride (strong). In the glucose reduction process, we
      obtained smaller size nanoparticles in comparison to the nanoparticles obtained
      in the borohydride reduction process under the same condition. Solvation dynamics
      study showed that reverse micellar aggregated structures were present after the
      nanoparticles' formation in a perturbed state. Nanoparticles inside the reverse
      micellar core were responsible for this perturbation. Larger size nanoparticles
      were triggering larger perturbation than the smaller size nanoparticles. These
      changes in perturbation were also reflected clearly in solvation dynamics and
      rotational relaxation measurements.

PMID- 22380921
TI  - Bio-processing of agro-byproducts to animal feed.
AB  - Agricultural and food-industry residues constitute a major proportion (almost
      30%) of worldwide agricultural production. These wastes mainly comprise
      lignocellulosic materials, fruit and vegetable wastes, sugar-industry wastes as
      well as animal and fisheries refuse and byproducts. Agro-residues are rich in
      many bioactive and nutraceutical compounds, such as polyphenolics, carotenoids
      and dietary fiber among others. Agro residues are a major valuable biomass and
      present potential solutions to problems of animal nutrition and the worldwide
      supply of protein and calories, if appropriate technologies can be used for their
      valorization by nutrient enrichment. Technologies available for protein
      enrichment of these wastes include solid substrate fermentation, ensiling, and
      high solid or slurry processes. Technologies to be developed for the reprocessing
      of these wastes need to take account of the peculiarities of individual wastes
      and the environment in which they are generated, reprocessed, and used. In
      particular, such technologies need to deliver products that are safe, not just
      for animal feed use, but also from the perspective of human feeding. This review
      focuses on the major current applications of solid-state fermentation in relation
      to the feed sector.

PMID- 22380920
TI  - Cost-effectiveness of a vocational enablement protocol for employees with hearing
      impairment; design of a randomized controlled trial.
AB  - BACKGROUND: Hearing impairment at the workplace, and the resulting psychosocial
      problems are a major health problem with substantial costs for employees,
      companies, and society. Therefore, it is important to develop interventions to
      support hearing impaired employees. The objective of this article is to describe
      the design of a randomized controlled trial evaluating the (cost-) effectiveness
      of a Vocational Enablement Protocol (VEP) compared with usual care.
      METHODS/DESIGN: Participants will be selected with the 'Hearing and Distress
      Screener'. The study population will consist of 160 hearing impaired employees.
      The VEP intervention group will be compared with usual care. The VEP integrated
      care programme consists of a multidisciplinary assessment of auditory function,
      work demands, and personal characteristics. The goal of the intervention is to
      facilitate participation in work. The primary outcome measure of the study is
      'need for recovery after work'. Secondary outcome measures are coping with
      hearing impairment, distress, self-efficacy, psychosocial workload, job control,
      general health status, sick leave, work productivity, and health care use.
      Outcome measures will be assessed by questionnaires at baseline, and 3, 6, 9, and
      12 months after baseline. The economic evaluation will be performed from both a
      societal and a company perspective. A process evaluation will also be performed.
      DISCUSSION: Interventions addressing occupational difficulties of hearing
      impaired employees are rare but highly needed. If the VEP integrated care
      programme proves to be (cost-) effective, the intervention can have an impact on
      the well-being of hearing impaired employees, and thereby, on the costs for the
      company as well for the society. TRIAL REGISTRATION: Netherlands Trial Register
      (NTR): NTR2782.

PMID- 22380922
TI  - Effect of tibial plateau leveling osteotomy on femorotibial subluxation: in vivo
      analysis during standing.
AB  - OBJECTIVE: To assess the effect of tibial plateau leveling osteotomy (TPLO) on
      femorotibial subluxation during standing in dogs with cranial cruciate ligament
      (CrCL) insufficiency. STUDY DESIGN: Prospective clinical study. ANIMALS: Fifteen
      dogs weighing 20-45 kg with unilateral complete CrCL insufficiency. METHODS:
      Force-platform analysis, and lateral weight-bearing radiographs of the affected
      stifle were acquired preoperatively, 1, 3, and 6 months postoperatively. The
      distance between the origin and insertion of the CrCL (CrCL(d) ) was measured on
      each radiograph and compared between time points using ANOVA. Lateral radiographs
      of the non-weight-bearing affected stifle and weight-bearing contralateral normal
      stifle were acquired preoperatively, and CrCL(d)  was compared with a paired t
      test. Dogs were grouped according to medial meniscal status (intact or
      hemimeniscectomy) and CrCL(d)  was compared within each group using ANOVA.
      RESULTS: No difference was observed in CrCL(d)  between the non-weight-bearing
      affected stifle and the contralateral stifle (P = .994). That is, femorotibial
      joint alignment in the affected stifle when non-weight-bearing was considered
      normal. Preoperatively in the affected stifle, CrCL(d)  during weight-bearing was
      6.3 +/- 2.4 mm longer than normal (P < .001). Postoperative weight-bearing
      CrCL(d)  in dogs with intact menisci at all time points was not statistically
      different from normal; CrCL(d)  at 1 (P = .014) and 6 months (P = .005)
      postoperatively was longer than normal in dogs with hemimeniscectomy.
      CONCLUSIONS: TPLO does not consistently resolve femorotibial subluxation during
      standing in dogs with CrCL insufficiency. The medial meniscus appears to be an
      important contributor to stability in stifles treated by TPLO.

PMID- 22380923
TI  - Three Arabidopsis AIL/PLT genes act in combination to regulate shoot apical
      meristem function.
AB  - The shoot apical meristem, a small dome-shaped structure at the shoot apex, is
      responsible for the initiation of all post-embryonic shoot organs. Pluripotent
      stem cells within the meristem replenish themselves and provide daughter cells
      that become incorporated into lateral organ primordia around the meristem
      periphery. We have identified three novel regulators of shoot apical meristem
      activity in Arabidopsis thaliana that encode related AIL/PLT transcription
      factors: AINTEGUMENTA (ANT), AINTEGUMENTA-LIKE6 (AIL6)/PLETHORA3 (PLT3) and
      AINTEGUMENTA-LIKE7 (AIL7)/PLETHORA7 (PLT7). Loss of these genes results in plants
      that initiate only a few leaves prior to termination of shoot apical meristem
      activity. In 7-day-old ant ail6 ail7 seedlings, we observed reduced cell division
      in the meristem region, differentiation of meristematic cells and altered
      expression of the meristem regulators WUSCHEL (WUS), CLAVATA3 (CLV3) and SHOOT
      MERISTEMLESS (STM). Genetic experiments suggest that these three AIL genes do not
      act specifically in either the WUS/CLV or STM pathway regulating meristem
      function. Furthermore, these studies indicate that ANT, AIL6 and AIL7 have
      distinct functions within the meristem rather than acting in a strictly redundant
      manner. Our study thus identifies three new genes whose distinct functions are
      together required for continuous shoot apical meristem function.

PMID- 22380924
TI  - Effects of cigarette smoke and ethanol intake on mouse oesophageal mucosa changes
      induced by dietary zinc deficiency and deoxycholic acid supplementation.
AB  - The noxious effects of dietary zinc deficiency (ZD) and deoxycholic bile acid
      (DCA) supplementation in the oesophagus were investigated. The additional
      influence of cigarette smoke and ethanol intake on the changes in the oesophageal
      mucosa induced by dietary ZD plus DCA was also assessed. Male C57BL/6 mice were
      allocated into four groups: Group 1 was fed control diet and groups 2-4 were fed
      ZD plus DCA diet. After 5 weeks, groups 3 and 4 were exposed to 10% ethanol
      intake or cigarette smoke for 15 weeks, respectively. All animals were euthanized
      at the end of week 20, and the oesophagus, lung, liver and colon were collected
      and analysed by conventional morphology. Cell proliferation was assessed in the
      oesophageal mucosa by Ki-67 immunohistochemistry and cyclooxygenase 2 (COX-2)
      protein by Western blotting. Dietary ZD plus DCA treatment induced mild
      hyperkeratosis and hyperplasia, increased cell proliferation index and COX-2
      protein expression in the oesophagus, and intranuclear inclusion, karyocytomegaly
      and microvesicular fatty change in the liver. Cigarette smoke increased COX-2
      protein expression in oesophageal mucosa and irregular enlargement of alveolus
      and alveolar ductal air spaces, while ethanol enhanced liver damage induced by ZD
      plus DCA diet. These findings indicate that dietary ZD plus DCA treatment during
      20 weeks induces a pattern of chemical oesophageal injury but not Barrett's-like
      lesions.

PMID- 22380926
TI  - In vivo antioxidant activities of essential oils and their constituents from
      leaves of the Taiwanese Cinnamomum osmophloeum.
AB  - Cinnamomum osmophloeum Kaneh is an indigenous tree species in Taiwan. In this
      study, phytochemical characteristics and antioxidant activities of the essential
      oils and key constituents from the leaves of two C. osmophloeum clones were
      investigated. The two trees possess two chemotypes, which were classified as the
      cinnamaldehyde type and camphor type. We demonstrated that the essential oils
      from C. osmophloeum leaves exerted in vivo antioxidant activities in
      Caenorhabditis elegans. In addition, trans-cinnamaldehyde and D-(+)-camphor,
      which respectively represent the major compounds in the cinnamaldehyde-type and
      camphor-type trees, exerted significant in vivo antioxidant activities against
      juglone-induced oxidative stress in C. elegans. Moreover, expressions of
      antioxidative-related genes, including superoxide dismutase (SOD) and glutathione
      S-transferase (GST), were significantly induced by trans-cinnamaldehyde and D-(+)
      camphor from C. osmophloeum leaves. Our results showed that the essential oils
      from C. osmophloeum leaves and their major compounds might have good potential
      for further development as nutraceuticals or antioxidant remedies.

PMID- 22380927
TI  - International collaborations preparing for a cancer "moon shot": a summary of the
      Sino-US Symposium on Head and Neck Cancer.
AB  - Oncologists and scientists in the field of head and neck cancer exchanged their
      research findings and clinical experiences in the Sino-USA Symposium on Head and
      Neck Cancer, which was held January 6-7, 2012 in Guangzhou, China. The symposium
      was jointly organized by Sun Yat-sen University Cancer Center (SYSUCC) and the
      University of Texas MD Anderson Cancer Center (MDACC). The Guangdong Provincial
      Anti-Cancer Association and the Chinese Journal of Cancer also helped in
      organizing the conference. Speakers were from China (SYSUCC, the Chinese
      University of Hong Kong, Tianjin Medical University Cancer Institute and
      Hospital, and Fudan University Shanghai Cancer Center) and the United States
      (MDACC). The presentations covered most kinds of head and neck cancers and
      included both basic and clinical research progress. In particular, NPC was
      discussed in depth. The symposium explored the reality that cancer is complex and
      numerous questions remain to be answered, even though there has already been an
      enormous effort into research. International exchanges of experience and in-depth
      cooperation are definitely needed to improve our capability of caring for cancer
      patients. In this article, we provide highlights of the presentations.

PMID- 22380928
TI  - Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an
      autocrine manner.
AB  - Molecules highly expressed in tumor endothelial cells (TEC) are important for
      specific targeting of these cells. Previously, using DNA microarray analysis, we
      found that the prostacyclin receptor (IP receptor) gene was upregulated in TEC
      compared with normal endothelial cells (NEC). Although prostacyclin is implicated
      in re-endothelialization and angiogenesis, its role remains largely unknown in
      TEC. Moreover, the effect of the IP receptor on TEC has not been reported. In the
      present study we investigated the function of the IP receptor in TEC. The TEC
      were isolated from two types of human tumor xenografts in nude mice, while NEC
      were isolated from normal counterparts. Prostacyclin secretion levels in TEC were
      significantly higher than those in NEC, as shown using ELISA. Real-time RT-PCR
      showed that the IP receptor was upregulated in TEC compared with NEC.
      Furthermore, migration and tube formation of TEC were suppressed by the IP
      receptor antagonist RO1138452. Immunohistostaining showed that the IP receptor
      was specifically expressed in blood vessels of renal cell carcinoma specimens,
      but not in glomerular vessels of normal renal tissue. These findings suggest that
      the IP receptor is a TEC-specific marker and might be a useful therapeutic
      target.

PMID- 22380929
TI  - The impact of open and closed mindsets on evaluative priming.
AB  - In the present research, we argue that open versus closed mindsets, accompanying
      ongoing versus completed mental jobs on the prime, determine the size of
      congruity effects in the evaluative priming paradigm. More specifically, we
      hypothesised that disfluent primes that resist an easily completed encoding
      process should induce an open mindset and thereby result in stronger congruity
      effects than fluent primes that induce closed mindsets. Across two experiments,
      we applied two different manipulations of prime fluency: gradual demasking
      (experiment 1) and colour contrast (experiment 2). As expected, in both
      experiments we found robust congruity effects, but only on trials with disfluent
      (vs. fluent) primes. Results of a follow-up experiment suggest that these effects
      are not due to attentional processes. We conclude that the mindsets resulting
      from individuals' activities during encoding are crucial in determining the
      outcome of evaluative priming effects.

PMID- 22380930
TI  - Test anxiety inventory: 30 years later.
AB  - Research suggests that test anxiety is associated with a number of maladaptive
      factors. The majority of test anxiety research includes the Test Anxiety
      Inventory (TAI) as a primary outcome variable. However, the TAI was normed on
      college undergraduates in 1980. The academic landscape has altered in a variety
      of ways in the past 30 years, which may result in out-of-date norms. This study
      examined changes in TAI scores in college undergraduates (n =437) as well as
      convergent validity with measures of trait anxiety and academic performance.
      Results indicated increases in TAI scores for females while holding constant for
      males. Additionally, females and males displayed positive correlations between
      the TAI and state-trait anxiety inventory, while only females displayed a
      significant negative correlation between the TAI and grade point average. Data
      provide evidence of changes in TAI scores. As a result, researchers should be
      careful when drawing conclusions based on original TAI norms, especially in the
      case of female undergraduates.

PMID- 22380931
TI  - Investigation on the structure of water/AOT/IPM/alcohols reverse micelles by
      conductivity, dynamic light scattering, and small angle X-ray scattering.
AB  - We have systematically investigated the effect of alcohols (ethanol, propanol,
      butanol, and pentanol) on the structure of the water/AOT/IPM system using
      conductivity, dynamic light scattering (DLS), and small-angle X-ray scattering
      (SAXS) techniques. The results show that no percolation phenomenon is observed in
      the water/AOT/IPM system, whereas the addition of ethanol (propanol and butanol)
      induces apparently percolation. The threshold water content (W(p)) depends
      closely on the alcohol type and concentration. The effect of alcohols on the
      conductance behavior is discussed from the physical properties of alcohols, the
      interfacial flexibility, and the attractive interactions between droplets. The
      hydrodynamic diameter of droplets (d(H)) obtained from DLS increases markedly
      with the increase in water content (W(0)); however, it decreases gradually with
      increasing alcohol chain length and concentration. SAXS measurements display
      distinctly the shoulder, the low hump peaks, and the heavy tail phenomenon in the
      pair distance distribution function p(r) profile, which rely strongly on the
      alcohol species and its concentration. The gyration radius (R(g)) increases with
      increasing W(0), and decreases with the increase of alcohol chain length and
      concentration. Schematic diagram of the conductance mechanism of
      water/AOT/IPM/alcohol systems is primarily depicted. Three different phases of
      the discrete droplets, the oligomers, and the isolated ellipsoidal droplets
      existed in the different W(0) ranges correspond to three different stages in the
      conductivity-W(0) curve. Coupling the structure characteristics of reverse
      micelles obtained from DLS and SAXS techniques with conductivity could be greatly
      helpful to deeply understand the percolation mechanism of water/AOT/IPM/alcohols
      systems.

PMID- 22380932
TI  - Living as an adolescent with HIV in Zambia -- lived experiences, sexual health
      and reproductive needs.
AB  - HIV services in developing countries are often ill-equipped to address the
      specific needs of HIV-positive adolescents. Studies suggest a lack of consistent,
      age-appropriate support regarding sexuality, relationships and transitioning to
      adulthood. The aims of this study were to explore and document the informational,
      psychosocial, sexual and reproductive health (SRH) needs of adolescents (aged 10
      19 years) living with HIV in Zambia, and identify gaps between these needs and
      existing services. This paper reports a qualitative explorative study. Semi
      structured interviews and focus group discussions were conducted with 111 HIV
      positive adolescents and 59 key informants, including health care workers (n=38)
      and parents/guardians (n=21). Participants were selected via a purposive sampling
      method. Three sites - Lusaka, Kitwe and Kalomo - were selected to ensure a broad
      representation of service-delivery settings in Zambia. Data were entered into
      NVIVO (QSR International) software, and analysed inductively to extract key
      themes, gather results and draw conclusions. Findings confirm that social
      networks have significant impact on treatment adherence and assist adolescents in
      coming to terms with an HIV diagnosis. The trauma of diagnosis, however, is
      exacerbated if poorly managed. Nevertheless, many adolescents are determined not
      to let HIV change their lives. They want to know SRH and HIV information, but
      service providers do not often adequately meet these informational needs. Where
      available, tailored and participatory events around HIV and SRH are greatly
      appreciated. Services that are welcoming, empowering and provide tailored
      information are highly valued. Adolescents living with HIV require effective,
      targeted and sustainable HIV services to navigate safely through adolescence.

PMID- 22380933
TI  - The contact sensitizer diphenylcyclopropenone has adjuvant properties in mice and
      potential application in epicutaneous immunotherapy.
AB  - BACKGROUND: Epicutaneous vaccination has gained increasing interest during the
      past decade as it offers a safe, needle-free, and patient-friendly alternative to
      invasive vaccine administrations. Recently, the safety and early efficacy of
      epicutaneous immunotherapy were also demonstrated in patients with hay fever, as
      an alternative to conventional subcutaneous allergen-specific immunotherapy
      (SCIT). One major challenge to epicutaneous vaccination is the barrier function
      of the stratum corneum, which must be overcome either by abrasive methods or by
      hydration. Such barrier function of the stratum corneum also hampers the use of
      common adjuvants used to enhance the efficacy of vaccination. METHODS: In a mouse
      model of allergy, we tested the adjuvant potential of diphenylcyclopropenone
      (DCP), a strong contact sensitizer, which is currently used for the treatment of
      a T cell-mediated hair loss disease (alopezia areata). RESULTS:
      Diphenylcyclopropenone enhanced antigen-specific IgG2a antibody responses as well
      as IL-10 cytokine production after epicutaneous immunization with ovalbumin
      (OVA). Epicutaneous allergen-specific immunotherapy (EPIT) with OVA and DCP also
      protected sensitized mice from anaphylaxis and asthma. The protective effect was
      more robust than that of conventional SCIT, which did not significantly alleviate
      the symptoms of allergy in the murine models of anaphylaxis and asthma.
      CONCLUSIONS: This preclinical study confirmed previous clinical data that have
      demonstrated the potential of the skin as a target for allergen immunotherapy.
      The study also suggests that epicutaneous immunization or immunotherapy can be
      improved when an appropriate adjuvant such as DCP is used.

PMID- 22380934
TI  - Reaction of metal-binding ligands with the zinc proteome: zinc sensors and
      N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine.
AB  - The commonly used Zn(2+) sensors 6-methoxy-8-p-toluenesulfonamidoquinoline (TSQ)
      and Zinquin have been shown to image zinc proteins as a result of the formation
      of sensor-zinc-protein ternary adducts not Zn(TSQ)(2) or Zn(Zinquin)(2)
      complexes. The powerful, cell-permeant chelating agent N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN) is also used in conjunction with these and
      other Zn(2+) sensors to validate that the observed fluorescence enhancement seen
      with the sensors depends on intracellular interaction with Zn(2+). We
      demonstrated that the kinetics of the reaction of TPEN with cells pretreated with
      TSQ or Zinquin was not consistent with its reaction with Zn(TSQ)(2) or
      Zn(Zinquin)(2). Instead, TPEN and other chelating agents extract between 25 and
      35% of the Zn(2+) bound to the proteome, including zinc(2+) from zinc
      metallothionein, and thereby quench some, but not all, of the sensor-zinc-protein
      fluorescence. Another mechanism in which TPEN exchanges with TSQ or Zinquin to
      form TPEN-zinc-protein adducts found support in the reactions of TPEN with
      Zinquin-zinc-alcohol dehydrogenase. TPEN also removed one of the two Zn(2+) ions
      per monomer from zinc-alcohol dehydrogenase and zinc-alkaline phosphatase,
      consistent with its ligand substitution reactivity with the zinc proteome.

PMID- 22380935
TI  - Evaluation of osteoarthritis in cats: novel information from a pilot study.
AB  - OBJECTIVE: To describe structural changes associated with osteoarthritis (OA) in
      cats and to quantify OA-associated disability using functional evaluations. STUDY
      DESIGN: Cross-sectional pilot study with longitudinal data. ANIMALS: Normal cats
      (n = 2) and coxofemoral joint OA cats (n = 4) were evaluated by physical
      examination, radiography, and magnetic resonance imaging (MRI). METHODS:
      Structural changes related to OA were scored using computed radiographs (CR) and
      MRI. Functional evaluation consisted of podobarometric gait analyses performed
      using a pressure-sensitive mattress and motor activity assessments using collar
      attached, accelerometer-based activity sensors. RESULTS: Structural scores for
      the coxofemoral joint OA-related lesions were lower in normal cats than OA cats
      for MRI (P = .07). Use of MRI allowed for whole-organ assessment of the
      coxofemoral joint. Pelvic limb peak vertical ground reaction force (PVF) was
      higher in normal cats than OA cats (P = .10). During the night, motor activity
      was greater in normal cats than OA cats (P = .04). PVF was positively correlated
      with mean motor activity (Spearman coefficient [Rho] = 0.83, P = .04) and
      negatively correlated with age and MRI structural score (Rho = -0.93 and -0.79, P
      < .01 and .06, respectively). CONCLUSIONS: This study provides the first
      description of OA-related lesions in cats using MRI. Gait analysis and
      accelerometry should be considered as objective tools to characterize OA
      associated disability, although these assessments were weakly correlated with
      structural changes.

PMID- 22380936
TI  - Residues of sulfadiazine and doxycycline in egg matrices due to cross
      contamination in the feed of laying hens and the possible correlation with
      physicochemical, pharmacokinetic and physiological parameters.
AB  - In the poultry industry, the widespread use of veterinary drugs such as
      antimicrobial compounds may lead to the presence of residues in whole eggs, egg
      white and egg yolk. During this study, laying hens received experimental feed
      containing sulfadiazine or doxycycline at cross-contamination levels of 2.5%, 5%
      and 10% of the therapeutic concentration. Since the therapeutic dose is 250 mg
      kg(-1) for both substances, cross-contamination concentrations in the feed of
      6.25, 12.5 and 25 mg kg(-1) were expected. Whole egg, egg white and egg yolk
      samples were collected during the treatment and depletion period and were
      analysed via liquid chromatography-tandem mass spectrometry. For both drugs, a
      plateau phase was reached within 3-5 days and residue concentrations were
      detected in all egg matrices. For the 10% cross-contamination group, residual
      sulfadiazine concentrations of 208, 299 and 60 ug kg(-1) and residual doxycycline
      concentrations of 455, 332, 206 ug kg(-1) were detected in whole egg, egg white
      and egg yolk on day 13 of the treatment period, respectively. Both sulfadiazine
      and doxycycline had higher concentrations in egg white than in egg yolk, but the
      egg white-egg yolk ratio was higher for sulfadiazine than for doxycycline. As
      neither drug is allowed in Belgium for use in laying hens, residues may pose food
      safety concerns.

PMID- 22380937
TI  - Evaluation of the healthy schools program: Part II. The role of technical
      assistance.
AB  - INTRODUCTION: Evidence-based technical assistance may be needed to implement
      recent federal policy to prevent childhood obesity through the schools. The
      Healthy Schools Program is the largest school-based obesity prevention program in
      the United States. The objectives of this study were to evaluate the role of the
      program's training and technical assistance and to explore other contributing
      factors in changing school policies, practices, and environments. METHODS: We
      analyzed interim progress of schools recruited during the 2007-2008 and 2008-2009
      school years as of December 2010. Schools reported progress through an online
      inventory of policies, practices, and school environment. We compared baseline
      inventories to the most recent follow-up and tracked both training attendance and
      contact with national experts. To identify the factors associated with progress,
      we performed regression analysis on school level and demographics, number of
      months between baseline and follow-up, and technical assistance. RESULTS: The
      amount of training and technical assistance was significantly associated with
      school progress, controlling for school level and demographics, number of months
      between baseline and follow-up, and school status at baseline. Although all types
      of schools saw progress, schools in the South had the most progress and urban
      schools had the least progress. CONCLUSION: Evidence-based training and technical
      assistance were associated with school progress in changing policies, practices,
      and environment to prevent childhood obesity.

PMID- 22380938
TI  - Evaluation of the healthy schools program: Part I. Interim progress.
AB  - INTRODUCTION: Federal and state policies identify schools as a setting to prevent
      childhood obesity, but schools need better health-promoting strategies. The
      objective of this study was to evaluate interim progress in schools receiving
      hands-on training from the Healthy Schools Program, the nation's largest school
      based program aimed at preventing childhood obesity. The 4-year program targets
      schools with predominantly low-income, African American, or Hispanic students.
      METHODS: In 2010 we assessed schools that enrolled in the 2007-2008 and 2008-2009
      school years. School representatives completed an inventory of 8 content areas:
      policy and systems, school meals, competitive foods and beverages, health
      education, physical education, physical activity outside of physical education,
      before- and after-school programs, and school employee wellness. Schools'
      baseline inventory was compared by t test with the most recent inventory
      available. RESULTS: Schools made significant changes in all content areas, and
      effect sizes were moderate to large. CONCLUSION: Participating schools improved
      environmental policies and practices to prevent childhood obesity. The program is
      a resource to implement recent federal and state policies.

PMID- 22380939
TI  - A simulation model for designing effective interventions in early childhood
      caries.
AB  - INTRODUCTION: Early childhood caries (ECC)--tooth decay among children younger
      than 6 years--is prevalent and consequential, affecting nearly half of US 5-year
      olds, despite being highly preventable. Various interventions have been explored
      to limit caries activity leading to cavities, but little is known about the long
      term effects and costs of these interventions. We developed a system dynamics
      model to determine which interventions, singly and in combination, could have the
      greatest effect in reducing caries experience and cost in a population of
      children aged birth to 5 years. METHODS: System dynamics is a computer simulation
      technique useful to policy makers in choosing the most appropriate interventions
      for their populations. This study of Colorado preschool children models 6
      categories of ECC intervention--applying fluorides, limiting cariogenic bacterial
      transmission from mothers to children, using xylitol directly with children,
      clinical treatment, motivational interviewing, and combinations of these--to
      compare their relative effect and cost. RESULTS: The model projects 10-year
      intervention costs ranging from $6 million to $245 million and relative
      reductions in cavity prevalence ranging from none to 79.1% from the baseline.
      Interventions targeting the youngest children take 2 to 4 years longer to affect
      the entire population of preschool-age children but ultimately exert a greater
      benefit in reducing ECC; interventions targeting the highest-risk children
      provide the greatest return on investment, and combined interventions that target
      ECC at several stages of its natural history have the greatest potential for
      cavity reduction. Some interventions save more in dental repair than their cost;
      all produce substantial reductions in repair cost. CONCLUSION: By using data
      relevant to any geographic area, this system model can provide policy makers with
      information to maximize the return on public health and clinical care
      investments.

PMID- 22380942
TI  - Functional characterization of ObgC in ribosome biogenesis during chloroplast
      development.
AB  - The Spo0B-associated GTP-binding protein (Obg) GTPase, essential for bacterial
      viability, is also conserved in eukaryotes, but its primary role in eukaryotes
      remains unknown. Here, our functional characterization of Arabidopsis and rice
      obgc mutants strongly underlines the evolutionarily conserved role of eukaryotic
      Obgs in organellar ribosome biogenesis. The mutants exhibited a chlorotic
      phenotype, caused by retarded chloroplast development. A plastid DNA macroarray
      revealed a plastid-encoded RNA polymerase (PEP) deficiency in an obgc mutant,
      caused by incompleteness of the PEP complex, as its western blot exhibited
      reduced levels of RpoA protein, a component of PEP. Plastid rRNA profiling
      indicated that plastid rRNA processing is defective in obgc mutants, probably
      resulting in impaired ribosome biogenesis and, in turn, in reduced levels of RpoA
      protein. RNA co-immunoprecipitation revealed that ObgC specifically co
      precipitates with 23S rRNA in vivo. These findings indicate that ObgC functions
      primarily in plastid ribosome biogenesis during chloroplast development.
      Furthermore, complementation analysis can provide new insights into the
      functional modes of three ObgC domains, including the Obg fold, G domain and OCT.

PMID- 22380943
TI  - Traumatic brain injury.

PMID- 22380945
TI  - Preparation of multilayered CdSe quantum dot sensitizers by electrostatic layer
      by-layer assembly and a series of post-treatments toward efficient quantum dot
      sensitized mesoporous TiO2 solar cells.
AB  - A multilayer of CdSe quantum dots (QDs) was prepared on the mesoporous surface of
      a nanoparticulate TiO(2) film by a layer-by-layer (LBL) assembly using the
      electrostatic interaction of the oppositely charged QD surface for application as
      a sensitizer in QD-sensitized TiO(2) solar cells. To maximize the absorption of
      incident light and the generation of excitons by CdSe QDs within a fixed
      thickness of TiO(2) film, the experimental conditions of QD deposition were
      optimized by controlling the concentration of salt added into the QD-dissolved
      solutions and repeating the LBL deposition a few times. A proper concentration of
      salt was found to be critical in providing a deep penetration of QDs into the
      mesopore, thus leading to a dense and uniform distribution throughout the whole
      TiO(2) matrix while anchoring the oppositely charged QDs alternately in a
      controllable way. A series of post-treatments with (1) CdCl(2), (2) thermal
      annealing, and (3) ZnS-coating was found to be very critical in improving the
      overall photovoltaic properties, presumably through a better connection between
      QDs, effective passivation of QD's surface, and a high impedance of
      recombination, which were proved by transmission electron microscopy (TEM) and
      electrochemical impedance spectroscopy (EIS) experiments. With a proper post
      treatment of multilayered QDs as a sensitizer, the overall power conversion
      efficiency in the CdSe QD-sensitized TiO(2) solar cells could reach 1.9% under
      standard illumination condition of simulated AM 1.5G (100 mW/cm(2)).

PMID- 22380944
TI  - alpha-terpineol reduces mechanical hypernociception and inflammatory response.
AB  - alpha-Terpineol (TPN), a volatile monoterpene alcohol, is relatively non-toxic
      and one of the major components of the essential oils of various plant species.
      In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or
      100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by
      carrageenan (CG, 300 MUg/paw) and the involvement of important mediators of its
      cascade signalling, such as tumour necrosis factor-alpha (TNF-alpha, 100 pg/paw),
      prostaglandin E2 (PGE2, 100 ng/paw) or dopamine (DA, 30 MUg/paw). We also
      investigated the anti-inflammatory effect of TPN on the model of carrageenan
      induced pleurisy and the LPS-induced nitrite production in murine macrophages.
      Pre-systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the
      development of mechanical hypernociception induced by CG or TNF-alpha. A similar
      effect was also observed upon PGE2 and DA administration. In addition, TPN
      significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10
      and 100 MUg/mL) also significantly reduced (p < 0.01) nitrite production in
      vitro. Our results provide information about the antinociceptive and anti
      inflammatory properties of TPN on mechanical hypernociception and suggest that
      this compound might be potentially interesting in the development of new
      clinically relevant drugs for the management of painful and/or inflammatory
      disease.

PMID- 22380946
TI  - Regulation of the metabolite profile by an APC gene mutation in colorectal
      cancer.
AB  - Mutation of the APC gene occurs during the early stages of colorectal cancer
      development. To obtain new insights into the mechanisms underlying the aberrant
      activation of the Wnt pathway that accompanies APC mutation, we carried out a gas
      chromatography-mass spectrometry-based semiquantitative metabolome analysis. In
      vitro experiments comparing SW480 cells expressing normal APC and truncated APC
      indicated that the levels of metabolites involved in the latter stages of the
      intracellular tricarboxylic acid cycle, including succinic acid, fumaric acid,
      and malic acid, were significantly higher in the SW480 cells expressing the
      truncated APC. In an in vivo study, we found that the levels of most amino acids
      were higher in the non-polyp tissues of APC(min/+) mice than in the normal
      tissues of the control mice and the polyp tissues of APC(min/+) mice. Ribitol,
      the levels of which were decreased in the polyp lesions of the APC(min/+) mice
      and the SW480 cells expressing the truncated APC, reduced the growth of SW480
      cells with the APC mutation, but did not affect the growth of SW480 transfectants
      expressing full-length APC. The level of sarcosine was found to be significantly
      higher in the polyp tissues of APC(min/+) mice than in their non-polyp tissues
      and the normal tissues of the control mice, and the treatment of SW480 cells with
      50 MUM sarcosine resulted in a significant increase in their growth rate. These
      findings suggest that APC mutation causes changes in energetic metabolite
      pathways and that these alterations might be involved in the development of
      colorectal cancer.

PMID- 22380947
TI  - Editorial: endoscopes and helmets: yes or no?

PMID- 22380948
TI  - Nonendoscopic, minimally invasive calvarial vault remodeling without
      postoperative helmeting for sagittal synostosis.
AB  - OBJECT: Multiple surgical procedures have been described for the management of
      isolated nonsyndromic sagittal synostosis. Minimally invasive techniques have
      been recently emphasized, but these techniques necessitate the use of an
      endoscope and postoperative helmeting. The authors assert that a safe and
      effective, more "minimalistic" approach is possible, avoiding the use of
      endoscopic visualization and routine postoperative application of a cranial
      orthosis. METHODS: A single-institution cohort analysis was performed on 18 cases
      involving infants treated for isolated nonsyndromic sagittal synostosis between
      2008 and 2010 using a nonendoscopic, minimally invasive calvarial vault
      remodeling (CVR) procedure without postoperative helmeting. The surgical
      technique is described. Variables analyzed were: age at time of surgery, sex,
      estimated blood loss (EBL), operative time, intraoperative complications,
      postoperative complications, length of stay, pre- and postoperative cephalic
      index (CI), clinical impressions, and results of a 5-question nonstandardized
      questionnaire administered to patient caregivers regarding outcome. RESULTS:
      Eleven male and 7 female infants (mean age 2.3 months) were included in the
      study. The mean duration of follow-up was 16.4 months (range 6-38 months). The
      mean procedural time was 111 minutes (range 44-161 minutes). The mean length of
      stay was 2.3 days (range 2-3 days). The mean EBL in all 18 patients was 101.4 ml
      (range 30-475 ml). One patient had significant bone bleeding resulting in an EBL
      of 475 ml. Excluding this patient, the mean EBL was 79.4 ml (range 30-150 ml).
      There were no deaths or intraoperative complications; one patient had a
      superficial wound infection. The mean CI was 69 preoperatively versus 79
      postoperatively, a statistically significant difference (p < 0.0001). Two
      patients were offered helmeting for suboptimal surgical outcome; one family
      declined and the single helmeted patient showed improvement at 2 months. No
      patient has undergone further surgery for correction of primary deformity,
      secondary deformities, or bony irregularities. Complete questionnaire data were
      available for 14 (78%) of the 18 patients; 86% of the respondents were pleased
      with the cosmetic outcome, 92% were happy to have avoided helmeting, 72% were
      doubtful that helmeting would have provided more significant correction, and 86%
      were doubtful that further surgery would be necessary. Small, palpable,
      aesthetically insignificant skull irregularities were reported by family members
      in 6 cases (43%). CONCLUSIONS: The authors present a nonendoscopic, minimally
      invasive CVR procedure without postoperative helmeting. Their small series
      demonstrates this to be a safe and efficacious procedure for isolated
      nonsyndromic sagittal synostosis, with improvements in CI at a mean follow-up of
      16.1 months, commensurate with other techniques, and with overall high family
      satisfaction. Use of a CVR cranial orthosis in a delayed fashion can be effective
      for the infrequent patient in whom this approach results in suboptimal
      correction.

PMID- 22380949
TI  - Editorial: arachnoid cysts.

PMID- 22380950
TI  - Endoscopic treatment of middle cranial fossa arachnoid cysts in children.
AB  - OBJECT: Arachnoid cysts located in the middle cranial fossa are common,
      comprising about half of all intracranial arachnoid cysts. The management of
      these cysts is challenging, and the optimal surgical treatment is controversial.
      This study evaluates the role of endoscopy in the treatment of middle cranial
      fossa arachnoid cysts (MCFACs) in children, focusing on some factors or technical
      aspects that might influence the outcome. METHODS: Thirty-two children with
      symptomatic MCFACs were the subject of this study. The group included 23 boys and
      9 girls, with a mean age of 3.6 years. All patients underwent operations using a
      purely endoscopic cystocisternostomy procedure through a transtemporal approach.
      RESULTS: Significant clinical improvement occurred in 28 cases (87.5%).
      Postoperative MR imaging showed a reduction in cyst size in 23 cases (71.9%),
      whereas in the remaining 9 cases (28.1%), the cyst size was unchanged. Minor
      intraoperative bleeding occurred in 3 cases (9.4%), which stopped spontaneously
      without any postoperative sequelae. Ipsilateral subdural hygroma occurred in 2
      cases (6.3%) and resolved within a few weeks without surgery; transient
      oculomotor palsy occurred in 1 case (3.1%). During follow-up (mean 4.6 years), 3
      patients (9.4%) experienced recurrence of symptoms and an increase in cyst size.
      Interestingly, all 3 patients who had recurrence had also experienced
      intraoperative bleeding at initial surgery. At a second endoscopic procedure, the
      fenestration was found to be closed in all 3 patients. CONCLUSIONS: Endoscopic
      cystocisternostomy is recommended in the treatment of MCFACs in children because
      it is simple, minimally invasive, and effective. It maintains the basic strategy
      of cyst fenestration into the basal cisterns without the invasiveness of open
      craniotomy. This procedure reduces operative and recovery times and is associated
      with low morbidity and mortality rates.

PMID- 22380951
TI  - Editorial: intraventricular hemorrhage and posthemorrhagic hydrocephalus.

PMID- 22380953
TI  - Intraoperative magnetic resonance imaging to reduce the rate of early reoperation
      for lesion resection in pediatric neurosurgery.
AB  - OBJECT: This study describes the pediatric experience with a dual-multifunction
      room IMRIS 1.5-T intraoperative magnetic resonance imaging (iMRI) suite and
      analyzes its impact on clinical variables associated with neurosurgical resection
      of intracranial lesions, including safety and efficacy. METHODS: Since the
      inception of the iMRI-guided resection program in April 2008 at both Barnes
      Jewish and St. Louis Children's Hospital, a prospective database recorded the
      clinical variables associated with demographics and outcome with institutional
      review board approval. A similarly approved retrospective database was
      constructed from February 2006 to March 2010 for non-iMRI resections. These
      databases were retrospectively reviewed for clinical variables associated with
      resection of pediatric (age 20 months-21 years) intracranial lesions including
      brain tumors and focal cortical dysplasia. Patient demographics, operative time,
      estimated blood loss, additional resection, length of stay, pathology, and
      complications were analyzed. RESULTS: The authors found that 42 iMRI-guided
      resections were performed, whereas 103 conventional resections had been performed
      without the iMRI. The mean patient age was 10.5 years (range 20 months-20 years)
      in the iMRI group and 9.8 years (range 2-21 years) in the conventional group (p =
      0.41). The mean duration of surgery was 350 minutes in the iMRI group and 243
      minutes in the conventional group (p < 0.0001). The mean hospital stay was 8.2
      days in the iMRI group, and 6.6 days in the conventional group, and this trended
      toward significance (p = 0.05). In the first 2 weeks postoperatively, there were
      8 reoperations (7.77%) in the conventional group compared with none in the iMRI
      group, which was not significant in a 2-tailed test (p = 0.11) but trended toward
      significance in a 1-tailed test (p = 0.06). The significant complications
      included reoperation for hydrocephalus or infection: 6.8% (conventional) versus
      4.8% (iMRI). CONCLUSIONS: Intraoperative MR imaging-guided resections resulted in
      a trend toward reduction in the need for repeat surgery in the immediate 2-week
      postoperative period compared with conventional pediatric neurosurgical
      resections for tumor or focal cortical dysplasia. Although there is an increased
      operative time, the iMRI suite offers a comparable safety and efficacy profile
      while potentially reducing the per-case cost by diminishing the need for early
      reoperation.

PMID- 22380954
TI  - Open fetal surgery for myelomeningocele.
AB  - In a recently completed randomized, prospective clinical trial, fetal repair for
      myelomeningocele was shown to result in reduced rates of hydrocephalus requiring
      placement of a ventriculoperitoneal shunt, improvement in Chiari malformation
      Type II, and improvement in neurological function compared with standard
      postnatal repair. Successful fetal surgery requires the active participation and
      interaction of several clinical teams. Each group has a specific role, and
      overlap is often required at different points of the treatment plan. Extensive
      multispecialty discussions with the patient and family are necessary before
      informed consent can be obtained. Fetal surgery carries significant risks to the
      mother and fetus and these must be carefully considered prior to a final
      treatment decision. This review will summarize the evaluation and treatment of
      patients undergoing fetal repair for myelomeningocele at one institution.

PMID- 22380952
TI  - Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and
      current treatment concepts.
AB  - OBJECT: Preterm infants are at risk for perinatal complications, including
      germinal matrix-intraventricular hemorrhage (IVH) and subsequent posthemorrhagic
      hydrocephalus (PHH). This review summarizes the current understanding of the
      epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm
      infants. METHODS: The MEDLINE database was systematically searched using terms
      related to IVH, PHH, and relevant neurosurgical procedures to identify
      publications in the English medical literature. To complement information from
      the systematic search, pertinent articles were selected from the references of
      articles identified in the initial search. RESULTS: This review summarizes the
      current knowledge regarding the epidemiology and pathophysiology of IVH and PHH,
      primarily using evidence-based studies. Advances in obstetrics and neonatology
      over the past few decades have contributed to a marked improvement in the
      survival of preterm infants, and neurological morbidity is also starting to
      decrease. The incidence of IVH is declining, and the incidence of PHH will likely
      follow. Currently, approximately 15% of preterm infants who suffer severe IVH
      will require permanent CSF diversion. The clinical presentation and surgical
      management of symptomatic PHH with temporary ventricular reservoirs (ventricular
      access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal
      shunts are discussed. Preterm infants who develop PHH that requires surgical
      treatment remain at high risk for other related neurological problems, including
      cerebral palsy, epilepsy, and cognitive and behavioral delay. This review
      highlights numerous opportunities for further study to improve the care of these
      children. CONCLUSIONS: A better grasp of the pathophysiology of IVH is beginning
      to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I
      and II studies to advance the outcomes of preterm infants. The need for well
      designed multicenter trials is essential because of the declining incidence of
      IVH and PHH, variations in referral patterns, and neonatal ICU and neurosurgical
      management. Well-designed multicenter trials will eventually produce evidence to
      enable neurosurgeons to provide their smallest, most vulnerable patients with the
      best practices to minimize perioperative complications and permanent shunt
      dependence, and most importantly, optimize long-term neurodevelopmental outcomes.

PMID- 22380955
TI  - Use of lumbar ultrasonography to detect occult spinal dysraphism.
AB  - OBJECT: Various cutaneous stigmata and congenital anomalies are accepted as
      sufficient reasons to perform lumbar ultrasonography as a screening tool to rule
      out occult spinal dysraphism (OSD). The purpose of this study was to correlate
      presenting cutaneous findings with lumbar ultrasonography results based on a
      large number of lumbar ultrasonography tests obtained by regional primary care
      providers. METHODS: Over the course of 5 years, 1273 infants underwent lumbar
      ultrasonography screening at a major pediatric tertiary referral center. Of these
      infants, 1116 had adequate documentation for retrospective chart review. Referral
      sources included urban academic, urban private practice, and surrounding rural
      private practitioners. Presence of cutaneous stigmata and/or congenital anomalies
      and lumbar ultrasonography results were reviewed for all patients. When present,
      surgical findings were reviewed. RESULTS: A total of 943 infants were referred
      for presumed cutaneous stigmata, the most common of which was a sacral dimple
      (638 patients [68%]) followed by hairy patch (96 patients [10%]). Other reported
      cutaneous findings included hemangioma, deviated gluteal fold, skin tag, and skin
      discoloration. In comparison, 173 patients presented with congenital anomalies,
      such as imperforate anus (56 patients [32%]) and tracheoesophageal
      fistula/esophageal atresia (37 patients [21%]), most of which were detected
      prenatally by fetal ultrasonography. A total of 17 infants underwent surgical
      exploration. Occult spinal dysraphism was diagnosed in 7 infants in the cutaneous
      stigmata group and in 10 infants in the group with congenital abnormalities. None
      of the cutaneous stigmata as recorded were found to be indicative of the presence
      of OSD. CONCLUSIONS: Cutaneous markers as currently defined by general
      practitioners are not useful markers for predicting OSD. The vast majority of
      findings on lumbar ultrasonography studies performed under these circumstances
      will be negative.

PMID- 22380956
TI  - Paciniolipoma in congenital spinal dysraphism.
AB  - The authors describe a case in which an intradural lipoma, causing tethering of
      the cord, was found on histological examination to exhibit fully differentiated
      mature pacinian corpuscles throughout. There are only 3 reports in the literature
      describing this rare tumor, and the authors use the term "paciniolipoma" to refer
      to it.

PMID- 22380957
TI  - Utility of electrodiagnostic testing and computed tomography myelography in the
      preoperative evaluation of neonatal brachial plexus palsy.
AB  - OBJECT: The rate of neonatal brachial plexus palsy (NBPP) remains 0.4%-4% despite
      improvements in perinatal care. Among affected children, the extent of brachial
      plexus palsy differs greatly, as does the prognosis. Controversial elements in
      management include indications and timing of nerve repair as well as type of
      reconstruction in patients in whom function will ultimately not be recovered
      without surgical intervention. Differentiating preganglionic (avulsion) from
      postganglionic (rupture) lesions is critical because preganglionic lesions cannot
      spontaneously recover motor function. Distinguishing between these lesions at
      initial presentation based on clinical examination alone can be difficult in
      infants. The purpose of the present study was to determine the sensitivity of
      preoperative electrodiagnostic studies (EDSs) and CT myelography (CTM) in
      determining the presence of nerve root rupture and avulsions in infants with
      NBPP. METHODS: After receiving institutional review board approval, the authors
      conducted a retrospective review of patients referred to the Neonatal Brachial
      Plexus Program between 2007 and 2010. Inclusion criteria included children who
      underwent brachial plexus exploration following preoperative EDSs and CTM. The
      CTM scans were interpreted by a staff neuroradiologist, EDSs were conducted by a
      single physiatrist, and intraoperative findings were recorded by the operating
      neurosurgeon. The findings from the preoperative EDSs and CTM were then compared
      with intraoperative findings. The sensitivities and 95% confidence intervals were
      determined to evaluate performance accuracy of each preoperative measure.
      RESULTS: Twenty-one patients (8 male amd 13 female) met inclusion criteria for
      this study. The sensitivity of EDSs and CTM for detecting a postganglionic
      rupture was 92.8% (CI 0.841-0.969) and 58.3% (CI 0.420-0.729), respectively. The
      sensitivity for EDSs and CTM for preganglionic nerve root avulsion was 27.8% (CI
      0.125-0.509) and 72.2% (CI 0.491-0.875), respectively. In cases in which both CTM
      and EDSs gave concordant results, the sensitivity for both modalities combined
      was 50.0% (CI 0.237-0.763) for avulsion and 80.8% (CI 0.621-0.915) for rupture.
      Overall, EDSs were most useful in identifying ruptures, particularly in the upper
      plexus, whereas CTM was most sensitive in identifying avulsions in the lower
      plexus. CONCLUSIONS: Knowledge of the spinal nerve integrity is critical for
      early management of patients with NBPP. Surgical management, in the form of nerve
      repair/reconstruction, and optimal prognostication of NBPP depend on the accurate
      diagnosis of the level and type of lesion. Both EDSs and CTM scans must always be
      interpreted in the context of a comprehensive evaluation of the patient. They
      provide supplemental information (in addition to the physical examination) for
      early detection of nerve root rupture and avulsion injuries, aiding surgical
      decision making and preoperative planning for NBPP. Continued advances in
      imaging, EDSs, and microsurgical nerve repair techniques will allow surgeons to
      achieve greater success for functional recovery in management of NBPP.

PMID- 22380958
TI  - Stereoelectroencephalography in the presurgical evaluation of focal epilepsy in
      infancy and early childhood.
AB  - OBJECT: The authors report on the use of stereoelectroencephalography (stereo
      EEG) in the presurgical electroclinical evaluation of infants and very young
      children with focal drug-resistant epilepsy. METHODS: Fifteen patients (9 girls
      and 6 boys, mean age 34.1 +/- 7.3 months, range 21-45 months), potentially
      candidates to receive surgical treatment for their focal drug-resistant epilepsy,
      were evaluated using stereo-EEG recording for a detailed definition of the
      epileptogenic zone. Stereoelectroencephalography was indicated because
      neuroradiological (brain MRI) and video-EEG data failed to adequately localize
      the epileptogenic zone. Stereotactic placement of multicontact intracerebral
      electrodes was preceded by the acquisition of all pertinent anatomical
      information from structural and functional MRI and from brain angiography,
      enabling the accurate targeting of desired structures through avascular
      trajectories. Stereoelectroencephalography monitoring attempted to record
      habitual seizures; electrical stimulations were performed to induce seizures and
      for the functional mapping of eloquent areas. Stereoelectroencephalography-guided
      microsurgery, when indicated, pointed to removal of the epileptogenic zone and
      seizure control. RESULTS: Brain MRI revealed an anatomical lesion in 13 patients
      (lobar in 2 cases, multilobar or hemispheric in 11 cases) and was unremarkable in
      2 patients. One patient underwent 2 stereo-EEG studies. The arrangement of the
      intracerebral electrodes was unilateral in all but 1 case. One patient died the
      day following electrode placement due to massive brain edema and profound
      hyponatremia of undetermined cause. In 8 cases intracerebral electrical
      stimulations allowed mapping of functionally critical areas; in 3 other cases
      that received purposeful placement of electrodes in presumably eloquent areas, no
      functional response was obtained. Of the 14 patients who completed stereo-EEG
      monitoring, 1 was excluded from surgery for multifocality of seizures and 13
      underwent operations. Postoperatively, 2 patients exhibited an anticipated,
      permanent motor deficit, 3 experienced a transient motor deficit, and 2
      experienced transient worsening of a preexisting motor deficit. Three patients
      developed a permanent homonymous hemianopia after posterior resections.
      Histological analysis revealed cortical malformations in 10 cases. Of the 10
      patients with a postoperative follow-up of at least 12 months, 6 (60%) were
      seizure-free (Engel Class Ia), 2 (20%) experienced a significant reduction of
      seizures (Engel Class II), and 2 (20%) were unchanged (Engel Class IV).
      CONCLUSIONS: The present study indicates that stereo-EEG plays a prominent role
      in the presurgical evaluation of focal epilepsies also in the first years of life
      and that it may offer a surgical option in particularly complex cases that would
      have scarcely benefitted from further medical treatment. Results of stereo-EEG
      guided resective surgery were excellent, with 80% of patients exhibiting a
      substantial improvement in seizures. In consideration of the potentially life
      threatening risks of major intracranial surgery in this specific age group, the
      authors recommend reserving stereo-EEG evaluations for infants with realistic
      chances of benefiting from surgery.

PMID- 22380959
TI  - Surgical treatment of focal inhibitory motor seizures.
AB  - The authors describe a rare case of a pediatric patient with focal inhibitory
      motor seizures (ictal paralysis) with the seizure focus in the primary motor
      cortex. Seizures were characterized by ictal paralysis of the contralateral limbs
      without loss of consciousness. The seizure focus and progression were examined
      using long-term video electroencephalography (EEG) monitoring and MR imaging.
      Invasive recordings of the ictal EEG revealed spike rhythms arising from the
      primary motor cortex, suggesting that seizures associated with paralysis can
      arise from hyperactivity in either positive or negative motor areas. Resection of
      the cortical area related to ictal onset resulted in a seizure-free status for
      the last 3 years.

PMID- 22380960
TI  - Surgical treatment for primary spinal aneurysmal bone cysts: experience from
      Children's Hospital Boston.
AB  - OBJECT: Spinal aneurysmal bone cysts (ABCs) constitute a rare and clinically
      challenging disease, primarily affecting the pediatric population. Information
      regarding the management of spinal ABCs remains sparse. In this study the authors
      review their experience with spinal ABCs at Children's Hospital Boston. METHODS:
      The medical records of all patients treated surgically for primary spinal ABCs
      between January 1998 and July 2010 were retrospectively reviewed. RESULTS:
      Fourteen cases were identified (6 males and 8 females, ages 5-19 years old). The
      ABCs were located throughout the spine, with an equal number in the thoracic and
      lumbar spine, and rarely in the cervical spine. The majority of patients
      presented with back pain, but neurological deficits and spinal deformity were
      common. A variety of radiographic techniques were used to establish the
      diagnosis, including needle biopsy. Preoperative selective arterial embolization
      was performed in 7 cases (50%), and the majority of cases required spinal
      instrumentation along with resection. Mean follow-up was 55.9 months (range 15
      154 months) after initial intervention. Two ABCs recurred (14%), at 9 months and
      8 years after incomplete initial resection, and the patients underwent
      reoperation. Complete resection was ultimately achieved in all cases. All
      patients were asymptomatic and neurologically intact at their last follow-up
      evaluation, and showed no evidence of deformity or recurrence on imaging.
      CONCLUSIONS: Computed tomography and MR imaging are adequate for an initial
      evaluation of spinal ABCs, although solid variants can present a diagnostic
      challenge. Given the high rates of recurrence with residual disease, complete
      obliteration of the lesion should be the goal of treatment. Preoperative
      embolization is often performed, although in the authors' opinion the degree of
      bleeding tends not to support its routine use. Long-term follow-up is warranted
      as recurrences can occur years after initial intervention. However, gross-total
      excision in conjunction with spinal stabilization, as needed, usually provides
      cure of the ABC and excellent long-term spinal alignment.

PMID- 22380961
TI  - Establishing successful cerebrospinal fluid flow for radioimmunotherapy.
AB  - Successful delivery of intraventricular radioimmunotherapy is contingent on
      adequate CSF flow. The authors present a patient with medulloblastoma in whom
      obstructed CSF flow was causing hydrocephalus, which was initially corrected by
      implantation of a programmable shunting device. While managing the hydrocephalus,
      an endoscopic third ventriculostomy (ETV) needed to be performed in a collapsed
      ventricular system to ensure adequate radioimmunotherapy distribution.   This 18
      month-old patient with medulloblastoma involving leptomeningeal dissemination
      presented for intraventricular radioimmunotherapy. A CSF (111)In-DTPA
      scintigraphy study obtained through the existing programmable
      ventriculoperitoneal shunt demonstrated activity in the lateral and third
      ventricles, but no activity over the cerebral convexities or spinal canal,
      consistent with obstruction at the level of the cerebral aqueduct. By
      maximization of ventricular size in a controlled setting, the patient was able to
      undergo a trial of ETV through very small ventricles. A postoperative CINE MR
      imaging study confirmed patent ETV. The pressure settings on the shunt were kept
      at the highest opening pressure (200 mm H(2)O) to maximize flow through the stoma
      and improve the distribution of CSF throughout the subarachnoid space. The CSF
      flow scintigraphy study was again performed, this time with tracer activity
      demonstrated down the thecal sac at 3 hours, and symmetrically over the cerebral
      convexities at 24 hours. The patient began weekly intraventricular administration
      of (131)I-3F8 therapy.   Successful rerouting of CSF flow for the purpose of
      therapeutic radioisotope administration is possible. Endoscopic third
      ventriculostomy can be considered in patients with programmable shunting devices;
      normal or slit ventricles do not preclude successful ETV.

PMID- 22380962
TI  - Role of endoscopic third ventriculostomy at infected cerebrospinal fluid shunt
      removal.
AB  - OBJECT: Cerebrospinal fluid shunt infection is distressing, especially in the
      pediatric population. Usually, infected CSF shunts are removed, and after
      temporary external CSF drainage, reinsertion of the CSF shunt is necessary.
      Unfortunately, it is not rare to encounter CSF reinfection after shunt renewal,
      and furthermore, the reinserted CSF shunt is at a considerable risk of
      malfunction. Endoscopic third ventriculostomy (ETV) is a potent option in
      managing CSF shunt infection, although ETV failure may occur more frequently when
      it is used to remove an infected shunt. The authors retrospectively evaluated CSF
      reinfection after using ETV during removal of infected CSF shunts; then the
      longevity of ETV and of successive reinserted ventriculoperitoneal shunts (VPSs)
      after ETV failure were also examined. METHODS: Children with shunted
      hydrocephalus were retrospectively reviewed, and data on their initial CSF shunt
      infections were extracted. Thirty-six children underwent VPS reinsertion (the VPS
      group), and 9 underwent ETV after removal of the infected CSF shunt (the ETV
      group). As the primary outcome, ETV efficacy against CSF reinfection within 6
      months was analyzed by comparing the reinfection rates, and the risk factors for
      CSF reinfection were analyzed by logistic regression. The longevity of the
      reinserted shunt in the VPS group was calculated using the Kaplan-Meier method,
      which was compared with ETV longevity as the secondary outcome, and also with the
      longevity of reinserted VPSs in the ETV group after ETV failure as the tertiary
      outcome. RESULTS: Reinfection of CSF was seen in 27.8% of children in the VPS
      group. Among 9 children in the ETV group, only 1 (11.1%) had CSF reinfection.
      However, logistic regression analysis failed to show that performing ETV was a
      significant factor protecting against CSF reinfection: the significant risk
      factors were younger age at reinsertion of VPS or ETV (p = 0.037) and a history
      of shunt revisions (p = 0.011). The longevity of reinserted VPSs in the VPS group
      was calculated to be 658 +/- 166.3 days (mean +/- SE). Longevity of ETV was
      compared in the analysis of the secondary outcome, which was 929.2 +/- 511.1
      days, and there were no significant differences between these durations. Only 2
      ETVs stayed patent, and a VPS was eventually implanted in the other 7 children.
      The longevity of this reinserted VPS in the ETV group, calculated based on these
      7 children, was 2011.1 +/- 540.7 days, which was confirmed to be longer than that
      in the VPS group (p = 0.031). CONCLUSIONS: Although the protective effect of
      using ETV during removal of an infected CSF shunt on reinfection is marginal, the
      ETV longevity can be considered equivalent to that of reinserted VPSs. Even if
      ETV failure occurs, the reinserted VPS has significantly better longevity than a
      VPS reinserted without using ETV, and use of ETV during infected CSF shunt
      removal can be considered a potent alternative or at least an adjunct to VPS
      reinsertion.

PMID- 22380963
TI  - De novo cerebral arteriovenous malformation in a child with previous cavernous
      malformation and developmental venous anomaly.
AB  - Although cerebral vascular malformations are traditionally considered to be
      congenital lesions, they often become clinically evident in the 3rd to 4th
      decades of life, leading to the assumption of a long silent clinical period.
      Unlike vein of Galen malformations, antenatal diagnosis of cerebral arteriovenous
      malformations (AVMs) is highly uncommon. Postnatal development of an AVM is an
      emergent concept supported by more clinical observations. Genetic and biological
      studies demonstrate that an environmental trigger ("second hit") in addition to
      genetic predisposition may be a key in understanding the pathophysiology of AVMs
      and other cerebral vascular lesions such as cavernous malformations (CMs). The
      authors describe a 6-year-old boy in whom a giant CM was diagnosed and a de novo
      AVM was detected 25 months after initial resection of the CM. This case seems to
      support the second-hit hypothesis.

PMID- 22380964
TI  - Rare basal vein fistula with dilated vein of Galen.
AB  - The authors present a rare case of arteriovenous fistula (AVF) of the basal vein
      of Rosenthal draining into a dilated vein of Galen managed by transarterial
      endovascular embolization. A male infant born at full term following a normal
      pregnancy and delivery with congestive heart failure, on investigation with MR
      imaging and MR angiography was found to have a basal vein of Rosenthal fistula
      with a dilated vein of Galen. His congestive heart failure was treated medically,
      and the AVF was managed electively at 10 months of age with successful
      transarterial endovascular embolization. The authors discuss the embryological
      aspects related to the pathological entity and the various clinical
      presentations, investigations, and management options. Management is primarily
      endovascular embolization; microsurgery is performed for a few selected cases,
      and radiosurgery has a limited role in older patients. Endovascular embolization
      is a safe and effective way to manage this malformation, with an excellent
      outcome if the AVF is eliminated by proper embolization at the fistulous point.

PMID- 22380965
TI  - Letter to the editor: tethered cord.

PMID- 22380966
TI  - Letter to the editor: endoscopy or microscopy?

PMID- 22380969
TI  - Foreword for Burkitt lymphoma special issue.

PMID- 22380971
TI  - Resolution of microscopic protonation enthalpies of polyprotic molecules by means
      of cluster expansions.
AB  - Cluster expansion techniques are used to obtain microconstants and
      microenthalpies of protonation reactions. The approach relies on the analysis of
      macroscopic protonation constants and protonation enthalpies within a homologous
      series. Various linear aliphatic polyamines are considered, including 3,4-tri
      (spermidine), 3,4,3-tet (spermine), and 2,2,2,2-pent. Besides the full resolution
      of the microscopic protonation equilibria, one obtains information on the
      temperature dependence of the microstate probabilities. We find that the
      concentrations of the dominant microspecies increase with increasing temperature.
      Due to the large negative protonation enthalpies that are typical for amines,
      higher temperatures generally favor the less protonated species.

PMID- 22380972
TI  - Evaluation of a method to characterize the phenolic profile of organic and
      conventional tomatoes.
AB  - The present study aims to compare the phenolic profiles of organic and
      conventional tomatoes bought in the market. For the quantification and
      identification of individual polyphenols, liquid chromatography coupled to mass
      spectrometry in tandem mode (LC-MS/MS) was carried out. Confirmation of the
      compounds previously identified on the triple-quadrupole was accomplished by
      injection in the high-resolution system (QToF-MS). In this way, 34 compounds were
      identified in tomato fruits. Recoveries of targeted polyphenols exceed 78% for
      conventional and organic tomatoes, respectively. The method intraday precision
      ranged between 3 and 5%, whereas the interday one was below 12%. Comparing the
      analyses of tomatoes from conventional and organic production systems
      demonstrated statistically higher levels (P < 0.05) of phenolic compounds in
      organic tomatoes. This methodology allowed finding differences in the bioactive
      components of organic and conventional tomatoes not previously reported.

PMID- 22380973
TI  - Strengthening families to support children affected by HIV and AIDS.
AB  - This paper provides an overview of the arguments for the central role of
      families, defined very broadly, and we emphasise the importance of efforts to
      strengthen families to support children affected by HIV and AIDS. We draw on work
      conducted in the Joint Learning Initiative on Children and AIDS's Learning Group
      1: Strengthening Families, as well as published data and empirical literature to
      provide the rationale for family strengthening. We close with the following
      recommendations for strengthening families to ameliorate the effects of HIV and
      AIDS on children. Firstly, a developmental approach to poverty is an essential
      feature of responses to protect children affected by HIV and AIDS, necessary to
      safeguard their human capital. For this reason, access to essential services,
      such as health and education, as well as basic income security, must be at the
      heart of national strategic approaches. Secondly, we need to ensure that support
      garnered for children is directed to families. Unless we adopt a family oriented
      approach, we will not be in a position to interrupt the cycle of infection,
      provide treatment to all who need it and enable affected individuals to be cared
      for by those who love and feel responsible for them. Thirdly, income transfers,
      in a variety of forms, are desperately needed and positively indicated by
      available research. Basic economic security will relieve the worst distress
      experienced by families and enable them to continue to invest in the health care
      and education of their children. Lastly, interventions are needed to support
      distressed families and prevent knock-on negative outcomes through programmes
      such as home visiting, and protection and enhancement of children's potential
      through early child development efforts.

PMID- 22380974
TI  - The demographic impact of HIV and AIDS across the family and household life
      cycle: implications for efforts to strengthen families in sub-Saharan Africa.
AB  - HIV is no longer a new or emerging disease in southern Africa. In the era of HIV
      and AIDS, families and households have continued to form, build, migrate and
      dissolve. Children born in the 1980s with the risk of mother-to-child HIV
      transmission have already gone on to start the next generation of families and
      households. Isolating the impact of HIV and AIDS on families and households is
      complex given that the epidemic has become part of the direction and force of
      contemporary demographic, social and economic processes and trends. Cycles of
      family and household life have occurred in a changing HIV and AIDS public-health
      environment, one in which HIV treatment access has increased rapidly. As part of
      an on-going process to assess the relevance and effectiveness of policies and
      programmes designed to protect and support children affected by HIV and AIDS, it
      is necessary to update our knowledge about the family and household circumstances
      in which children live. This paper summarises findings from a review on the
      "Demographic Evidence of Family and Household Changes in Response to the Effects
      of HIV/AIDS in Southern Africa: Implications for Efforts to Strengthen Families".
      The review examined published literature presenting data from empirical studies,
      primarily large, cross-sectional or longitudinal population-based or sample
      surveys. The family or household life-cycle is used as a conceptual and
      organisational framework. The implications of the demographic evidence are
      discussed in relation to policy and programme responses to strengthen families
      and households in the region.

PMID- 22380975
TI  - Extended family childcare arrangements in a context of AIDS: collapse or
      adaptation?
AB  - Families are subjected to a number of social, economic, political and demographic
      challenges. In recent years, the AIDS epidemic has constituted a major challenge
      for already poor families due to its wide reaching social, economic and health
      consequences. The devastating consequence of HIV and AIDS is being seen through
      the prolonged illness and death of family members of prime working age which
      impacts on family livelihoods and the ability to provide for and protect its
      members. This paper forms part of a review - commissioned by the Joint Learning
      Initiative on Children and HIV/AIDS - of qualitative studies of how families in
      southern Africa have changed, and are changing, as a result of the impact of HIV
      and AIDS. This paper presents results of how extended family childcare
      arrangements are changing as a result of the AIDS epidemic. In a southern African
      context, family denotes a wider array of relations than biological parents and
      their children - with children growing up amongst a multitude of relations
      sharing responsibility for their care and upbringing (Chirwa, 2002; Verhoef,
      2005). Recently, there has been growing interest in the capacity of the extended
      family to care for the increasing number of children whose parents have died.
      However, literature on the role of the extended family in caring for orphaned
      children remains contradictory. One approach - the social rupture thesis (Chirwa,
      2002) - suggests that the extended family network is collapsing under the strain
      of AIDS. On the other hand, families are portrayed as resilient and dynamic
      entities which are adapting their systems of childcare in response to the
      epidemic (Kuo,2007). In line with Abebe and Aase (2007) and Adams, Cekan, and
      Sauerborn (1998), this paper proposes a continuum of survival rather than a
      polarisation of extended family childcare arrangements.

PMID- 22380976
TI  - Multiple stressors in Southern Africa: the link between HIV/AIDS, food
      insecurity, poverty and children's vulnerability now and in the future.
AB  - Several countries in Southern Africa now see large numbers of their population
      barely subsisting at poverty levels in years without shocks, and highly
      vulnerable to the vagaries of the weather, the economy and government policy. The
      combination of HIV/AIDS, food insecurity and a weakened capacity for governments
      to deliver basic social services has led to the region experiencing an acute
      phase of a long-term emergency. "Vulnerability" is a term commonly used by
      scientists and practitioners to describe these deteriorating conditions. There is
      particular concern about the "vulnerability" of children in this context and
      implications for children's future security. Through a review of literature and
      recent case studies, and using a widely accepted conceptualisation of
      vulnerability as a lens, we reflect on what the regional livelihoods crisis could
      mean for children's future wellbeing. We argue that an increase in factors
      determining the vulnerability of households - both through greater intensity and
      frequency of shocks and stresses ("external" vulnerability) and undermined
      resilience or ability to cope ("internal" vulnerability) - are threatening not
      only current welfare of children, but also their longer-term security. The two
      specific pathways we explore are (1) erosive coping strategies employed by
      families and individuals; and (2) their inability to plan for the future. We
      conclude that understanding and responding to this crisis requires looking at the
      complexity of these multiple stressors, to try to comprehend their
      interconnections and causal links. Policy and programme responses have, to date,
      largely failed to take into account the complex and multi-dimensional nature of
      this crisis. There is a misfit between the problem and the institutional
      response, as responses from national and international players have remained
      relatively static. Decisive, well-informed and holistic interventions are needed
      to break the potential negative cycle that threatens the future security of
      Southern Africa's children.

PMID- 22380977
TI  - HIV/AIDS, declining family resources and the community safety net.
AB  - Families play central roles in the HIV/AIDS pandemic, caring for both orphaned
      children and the ill. This extra caregiving depletes two family resources
      essential for supporting children: time and money. We use recent data from
      published studies in sub-Saharan Africa to illustrate deficits and document
      community responses. In Botswana, parents caring for the chronically ill had less
      time for their preschool children (74 versus 96 hours per month) and were almost
      twice as likely to leave children home alone (53% versus 27%); these children
      experienced greater health and academic problems. Caregiving often prevented
      adults from working full time or earning their previous level of income; 47% of
      orphan caregivers and 64% of HIV/AIDS caregivers reported financial difficulties
      due to caregiving. Communities can play an important role in helping families
      provide adequate childcare and financial support. Unfortunately, while
      communities commonly offer informal assistance, the value of such support is not
      adequate to match the magnitude of need: 75% of children's families in Malawi
      received assistance from their social network, but averaging only US$81 annually.
      We suggest communities can strengthen the capacity of families by implementing
      affordable quality childcare for 0-6 year olds, after-school programming for
      older children and youth, supportive care for ill children and parents,
      microlending to enhance earnings, training to increase access to quality jobs,
      decent working conditions, social insurance for the informal sector, and income
      and food transfers when families are unable to make ends meet.

PMID- 22380978
TI  - Families, children, migration and AIDS.
AB  - Migration is very often a family affair, and often involves children, directly or
      indirectly. It may give rise to better quality of life for an entire family, or
      to bitter disappointment, and may also increase vulnerability to HIV and AIDS.
      This review, carried out for the Joint Learning Initiative on Children and AIDS,
      links the literature on "migration", on "HIV and AIDS" and on "families". Three
      themes are sketched: (1) As both HIV prevalence and circular migration increase,
      former migrant workers affected by AIDS may return to their families for care and
      support, especially at the end of life, often under crisis conditions. Families
      thus lose promising members, as well as sources of support. However, very little
      is known about the children of such migrants. (2) Following patterns of migration
      established for far different reasons, children may have to relocate to different
      places, sometimes over long distances, if their AIDS-affected parents can no
      longer care for them. They face the same adaptation challenges as other children
      who move, but complicated by loss of parent(s), AIDS stigma, and often poverty.
      (3) The issue of migrant families living with HIV has been studied to some
      extent, but mainly in developed countries with a long history of migration, and
      with little attention paid to the children in such families. Difficulties include
      involuntary separation from family members, isolation and lack of support,
      disclosure and planning for children's care should the parent(s) die and
      differences in treatment access within the same family. Numerous research and
      policy gaps are defined regarding the three themes, and a call is made for
      thinking about migration, families and AIDS to go beyond description to include
      resilience theory, and to go beyond prevention to include care.

PMID- 22380979
TI  - Evidence base for children affected by HIV and AIDS in low prevalence and
      concentrated epidemic countries: applicability to programming guidance from high
      prevalence countries.
AB  - As global commitment grows to protect and support children affected by HIV and
      AIDS, questions remain about how best to meet the needs of these children in low
      prevalence settings and whether information from high prevalence countries can
      appropriately guide programming in these settings. A 2007 search for the evidence
      in low prevalence settings on situational challenges of HIV and AIDS-affected
      children and interventions to address these challenges identified 413 documents.
      They were reviewed and judged for quality of documentation and scientific rigor.
      Information was compiled across eight types of challenges (health and health
      care, nutrition and food security, education, protection, placement, psychosocial
      development, socioeconomic status, and stigma/discrimination); and also assessed
      was strength of evidence for situational and intervention findings. Results were
      compared to three programming principles drawn from research in high prevalence
      countries: family-centered preventive efforts, treatment, and care; family
      focused support to ensure capacity to care for and protect these children; and
      sustaining economic livelihood of HIV and AIDS-affected households. Findings show
      that children affected by HIV and AIDS in low prevalence settings face increased
      vulnerabilities similar to those in high prevalence settings. These findings
      support seeking and testing programmatic directions for interventions identified
      in high prevalence settings. However, low prevalence settings/countries are
      extremely diverse, and the strength of the evidence base among them was mixed
      (strong, moderate, and weak in study design and documentation), geographically
      limited, and had insufficient evidence on interventions to draw conclusions about
      how best to reduce additional vulnerabilities of affected children. Information
      on family, economic, sociocultural, and political factors within local contexts
      will be vital in the development of appropriate strategies to mitigate
      vulnerabilities.

PMID- 22380980
TI  - Social protection to support vulnerable children and families: the potential of
      cash transfers to protect education, health and nutrition.
AB  - Investing in social protection in sub-Saharan Africa has taken on a new urgency
      as HIV and AIDS interact with other drivers of poverty to simultaneously
      destabilise livelihoods systems and family and community safety nets. Cash
      transfer programmes already reach millions of people in South Africa, and in
      other countries in southern and East Africa plans are underway to reach tens and
      eventually hundreds of thousands more. Cash transfers worldwide have demonstrated
      large impacts on the education, health and nutrition of children. While the
      strongest evidence is from conditional cash transfer evaluations in Latin America
      and Asia, important results are emerging in the newer African programmes. Cash
      transfers can be implemented in conjunction with other services involving
      education, health, nutrition, social welfare and others, including those related
      to HIV and AIDS. HIV/AIDS-affected families are diverse with respect to household
      structure, ability to work and access to assets, arguing for a mix of approaches,
      including food assistance and income-generation programmes. However, cash
      transfers appear to offer the best strategy for scaling up to a national system
      of social protection, by reaching families who are the most capacity constrained,
      in large numbers, relatively quickly. These are important considerations for
      communities hard-hit by HIV and AIDS, given the extent and nature of deprivation,
      the long-term risk to human capital and the current political willingness to act.

PMID- 22380981
TI  - Strengthening families through early intervention in high HIV prevalence
      countries.
AB  - Families have been at the forefront of the response to the HIV/AIDS epidemic in
      high-prevalence countries. They have also borne the greatest costs associated
      with the epidemic, including impoverishment, which has strained their capacity to
      care for vulnerable members. Within this context, there is consensus that
      strengthening the capacity of families to care for children is one of the most
      important strategies for mitigating the impacts of the HIV/AIDS epidemic on
      children's lives in high-prevalence countries. It is argued that evidence-based
      early intervention programmes that enhance caregiving and link caregivers with
      supports and services can play a pivotal role in strengthening families. Based on
      a systematic review, we recommend that two intervention strategies that should be
      given consideration within the context of high-prevalence countries, because of
      their demonstrated benefits in other settings, are nurse home visiting for first
      time, low-income pregnant mothers and their young children as well as early
      childhood development programmes for low-income children and families.

PMID- 22380982
TI  - Evidence-based gender findings for children affected by HIV and AIDS - a
      systematic overview.
AB  - This review (under the International Joint Learning Initiative on Children and
      AIDS) provides a detailed evidence analysis of gender, children and AIDS. Six
      systematic reviews provide the most up to date evidence base on research
      surrounding children and HIV on key topics of treatment resistance and adherence,
      schooling, nutrition, cognitive development and orphaning and bereavement.
      Traditional systematic review techniques were used to identify all published
      studies on four key topics, then studies were selected according to adequacy
      criteria (sufficient size, control group and adequate measures). A gender
      analysis was performed on included studies, detailing whether gender was
      measured, results were analysed by gender or any gender-based findings. For
      family studies, both the gender of the parents and gender of the child are
      needed. Secondary analysis by gender was performed on existing systematic reviews
      for treatment resistance and adherence. Of the 12 studies on treatment
      resistance, 11 did not look at gender. One found boys at a seven-fold risk
      compared to girls. For medication adherence, gender was not significant. Of the
      15 studies on schooling, 12 analysed findings by gender with an overall female
      disadvantage. Of the 14 studies on nutrition, nine analysed by gender with mixed
      findings. Of the 54 studies on cognitive development, 17 provided gender data,
      but only four analysed by gender with few differences established. Of the 15
      studies on bereavement, seven analysed data by gender again with mixed findings.
      Major policies fail to provide gender data for young children. WHO, UNAIDS and
      the international data sets are not gathered or coded by gender for young
      children (generally under 15 years of age) despite well-established gender
      challenges in later life. This review shows that the current evidence base is
      inadequate. Data on gender variation and outcome are urgently needed to inform
      policy and research on children and HIV.

PMID- 22380983
TI  - Consequences of HIV for children: avoidable or inevitable?
AB  - The HIV/AIDS epidemic has many serious consequences for children. These
      consequences are, however, rarely inevitable. Families can provide a protective
      barrier that deflects blows, or minimises their impact and a supportive nurturing
      environment that can help children recover from harm. If strong enough, and with
      sufficient access to quality services and support from communities, families can
      reduce the impacts of HIV/AIDS on children to negligible levels in most areas of
      impact. It is apparent that the impacts felt by children are not simply
      unfortunate, inevitable consequences of this epidemic. A strong and supported
      family with good access to quality services can deflect almost all of the impact.
      It is as a result of an interaction of the context of poverty, which weakens
      families, and a failure to adequately respond, that impacts are felt by children.

PMID- 22380984
TI  - Pholcodine in cough medicines and IgE-sensitization in the EU: an urgent task.

PMID- 22380985
TI  - Tyrosinase inhibitor and radical scavenger fractions and isolated compounds from
      aerial parts of Peucedanum knappii Bornm.
AB  - In this study, we investigated tyrosinase inhibitory and radical scavenger
      activities of the hydroalcoholic extract from Peucedanum knappii Bornm aerial
      parts, together with its fractions. The EtOAc fraction showed the highest
      antioxidant and anti-tyrosinase activity was selected for the isolation and
      identification of major active compound(s). Two flavonol glycosides, named
      rhamnetin-3-O-beta-D-glucopyranoside (1) and isorhamnetin-3-O-beta-D
      glucopyranoside (2) were isolated from the EtOAc fraction. Compound 1 showed the
      most active radical scavenging and potential anti-tyrosinase activity with SC50
      values of 2.9 ug mL(-1) on the DPPH test and IC50 27.95 ug mL(-1) in mushroom
      tyrosinase method. Therefore, isolated flavonoids from P. knappii can be
      considered as antioxidant and effective tyrosinase inhibitors.

PMID- 22380986
TI  - Potential application of serological tests on fluids from carcasses: detection of
      antibodies against Toxoplasma gondii and Sarcoptes scabiei in red foxes (Vulpes
      vulpes).
AB  - BACKGROUND: Serological surveys for disease investigation of wild animal
      populations require obtaining blood samples for analysis, which has logistic,
      ethic and economic difficulties. Applying serological test to fluids collected
      from dead animals is an alternative. The aim of this study was to assess if
      antibodies could be detected in two types of fluids collected from 56 carcasses
      of red foxes (Vulpes vulpes): pleural fluid and lung extract. FINDINGS: In 22
      (39%) foxes antibodies against Sarcoptes scabiei were detected in both fluid
      types by ELISA and Western blot. In 46 (82%) foxes, antibodies against Toxoplasma
      gondii were detected in pleural fluid and in 41 (73%) in lung extract applying a
      Toxo-screen test (DAT). Antibodies were still detectable in the same fluids kept
      at room temperature for 28 days, although in fewer foxes (16 and 14 foxes tested
      for T. gondii in lung extract and pleural fluid respectively; and 1 and 4 tested
      for S. scabiei in lung extract and pleural fluid respectively. CONCLUSIONS: These
      results indicate the potential utility of using fluids from carcasses for
      antibody screening of wild animals at the population level.

PMID- 22380987
TI  - Epidemiology and social networks.

PMID- 22380988
TI  - Microsurgical anatomy of the extracerebral segment of recurrent artery of Heubner
      in the Mexican population.
AB  - BACKGROUND: The recurrent artery of Heubner (RAH) is originated commonly from the
      anterior cerebral artery. Its extracerebral segment is directed toward the
      anterior perforate substance where it penetrates the cortex. METHODS: The RAH was
      dissected from 15 human brains from Mexican population, and the presence, length,
      branches, course and either RHAs or anterior communicating artery complex
      variants were reported. RESULTS: The RAH was found in 93% of the hemispheres and
      duplicated in 39% of the hemispheres. The RAH was duplicated in at least a
      hemisphere in 46.6% of the brains; 40% of the brains had a RAH in every
      hemisphere. It was duplicated in every hemisphere in 20%. A single artery at a
      hemisphere was found in 26.6% and double at the other hemisphere. With a length
      between 13.6 and 36.7 mm (mean: 24.2 mm) and giving rise to 1-9 branches (mean:
      3.9 branches), the RAH originated from the juxtacommunicating segment in 44% of
      the cases, from A2 in 41%, from A1 in 5% and as a branch of the frontopolar
      artery in 10%. It had an oblique course in 38%, an L in 31%, sinuous in 18% and
      an inverted L in 13%. In 53.3% of the brains, some variant of the anterior
      communicating artery complex was found. CONCLUSIONS: Because of the common
      anatomy of the RAH and its variants, we must consider the probability of finding
      it duplicated; therefore, it is necessary to make minute dissections of the
      region to locate or to secure the absence of the RAH.

PMID- 22380989
TI  - Laser-ranibizumab treatment for retinopathy of prematurity in umbral-preumbral
      disease. Three years of experience.
AB  - BACKGROUND: The "Early Treatment for Retinopathy of Prematurity Cooperative"
      reported a failure rate of 55.2% using laser in zone 1 for treatment of
      retinopathy of prematurity (ROP). We need to offer better alternatives for those
      patients. We undertook this study to evaluate the efficacy of combined laser
      ranibizumab therapy for ROP with threshold-prethreshold and "plus disease" and to
      study development of the newborn. METHODS: This is a prospective, experimental,
      longitudinal and open study including newborns of either <32 weeks of gestation
      or with a birth weight <1500 g, with threshold-prethreshold retinopathy or "plus
      disease." The effect of treatment was analyzed and development of the newborn was
      determined. RESULTS: We studied 34 eyes of 17 patients. Age at birth was 29.9 +/-
      2.6 weeks. Birth weight was 1,120 +/- 253 g. The statistics demonstrated an
      important relationship between severity of retinopathy and early birth age, along
      with a high probability of threshold-prethreshold disease at 29.4 weeks of age or
      1204 g birth weight. The Bayley scale reported normal development in 23.5% of
      cases, global retardation in 23.5%, psychomotor retardation but normal mental
      behavior in 29.4%, and mental retardation but normal psychomotor development in
      23.5%. We demonstrated regression of retinopathy in all cases. Persistence of
      vascular tortuosity was present in 17.6% of cases without vascular dilatation,
      and vitreous membrane development was demonstrated in 11.7% of patients.
      CONCLUSIONS: Laser-ranibizumab treatment has allowed a better control of
      retinopathy for threshold-prethreshold and "plus disease" in this group of
      patients.

PMID- 22380991
TI  - Experience with the "Cheatle-Henry" operation for femoral hernia repair.
AB  - BACKGROUND: The femoral hernia, the least common of all groin hernias, is seen
      most frequently in females. The main techniques for repair are femoral, inguinal
      and extraperitoneal Cheatle-Henry techniques. With laparoscopic surgery, total
      extraperitoneal technique is done with a patch to cover the femoral ring. We
      undertook this study to present the experience with the Cheatle-Henry operation
      for treatment of femoral hernia. METHODS: The study took place at the ABC
      Hospital, a third-level care institution in Mexico City. The study design was
      retrospective, observational, and descriptive. Medical records of patients with
      femoral hernias treated by the authors during a 27-year period utilizing the
      Cheatle-Henry operation were analyzed. RESULTS: Thirty-nine patients with femoral
      hernia treated with the Cheatle-Henry operation were found. There were 34 females
      (87.2%) and five males (12.8%) with an average age of 48 years, (range: 18-84
      years). Hernia was more common on the right side with 31 cases (79.48%). Elective
      surgery was done in 26 cases (66.65%) and emergency operations were done in 13
      patients (33.53%). There was no morbidity/mortality. CONCLUSIONS: Cheatle-Henry
      operation is a safe and secure technique to operate on femoral hernia, which is
      the least common of all groin hernias.

PMID- 22380990
TI  - Ab externo trabeculectomy performed under topical anesthesia supplemented by
      conscious sedation.
AB  - BACKGROUND: Ab externo trabeculectomy (AET) is the most common surgical procedure
      to treat glaucoma; topical anesthesia supplemented by conscious sedation is one
      of the diverse anesthetic methods to perform such type of surgery. The efficacy
      and safety of using topical anesthesia supplemented with conscious sedation for
      performing trabeculectomy were assessed in this prospective study. METHODS:
      Twenty-six eyes of 26 consecutive patients underwent trabeculectomy under the
      effect of topical anesthesia and sedation. All cases were prospectively assessed
      during five different intra-operative times in which the degree of pain was
      measured using a visual analog scale (VAS). RESULTS: One patient was excluded
      from the study due to excessive somnolence. Performing the iridectomy caused less
      tolerance (p = 0.03) but with acceptable scores according to the VAS (score 2 =
      minimal and tolerable pain; p = 0.02), followed by conjunctival closure
      (nonsignificant p values). The entire procedure did not cause either moderate to
      extreme pain (scores 4 and 5 of the scale, respectively) in any of the patients.
      Levels of pain, blood pressure, heart rate, and oxygen saturation were compared
      among the different intra-operative times. No statistically significant (p >0.05)
      differences were demonstrated. Eighty percent (n = 4) of the patients with green
      or blue iris had symptoms during the surgery, but this was of borderline
      statistical significance (p = 0.053). No ocular or systemic side effects appeared
      related to the reported anesthesia regime. CONCLUSIONS: Topical anesthesia
      associated with conscious sedation seems to be efficacious and safe and can be
      recommended for performing trabeculectomy.

PMID- 22380992
TI  - Autoclaved bone autograph reconstituted with autologous bone marrow.
AB  - BACKGROUND: Bone reconstruction is a common problem in the oncological setting.
      Mandibular reconstruction is done with microvascularized free flaps, but
      noticeable differences in shape and size exist in relation to the normal
      mandible; consequently, new reconstructive methods are desirable. We explored the
      feasibility of recovering osseous viability using a sterilized mandibular segment
      reconstituted with autologous bone marrow. METHODS: A 6- to 7-cm mandibular
      segment was excised in three Creole dogs. The segment was autoclaved for 40 min.
      The bone was then drilled, producing 3-mm holes every 10-mm. Bone was
      reconstituted with autologous bone marrow from the iliac spine mixed with
      particulated bone. Bone autograph was installed underneath the latissimus dorsi
      muscle. RESULTS: On week four after surgery, dogs received colloidal rhenium and
      were placed in a gamma camera. The study showed uptake of the radiotracer in the
      bone graft, demonstrating viability of bone marrow. One hour later, the autograph
      was excised in two dogs and a histopathological study corroborated the viability
      of the bone marrow and the formation of new vessels and osteoid. On week twelve,
      the third dog was administered MDP-99Tc and placed in a gamma camera. Results
      proved production of new bone. CONCLUSIONS: Osseous reconstruction with
      microvascularized flaps may cause problems, but sterilized bone reconstituted
      with bone marrow becomes viable. This observation eventually would allow osseous
      reconstruction, including the mandibule, easily and reliably in patients with
      osseous tumors. Autoclaved bone reconstituted with bone marrow recovers its
      viability.

PMID- 22380993
TI  - Enzymatic detergent in rat peritoneum. A comparative study with physiological
      solution.
AB  - BACKGROUND: Peritoneal washing out with physiological solution with different
      substances added is useful in peritoneal infections, but the effect of enzymatic
      detergents, such as quaternary didecyl-dimethyl ammonium compounds (DDAC), used
      in the sterilization of surgical material is unknown. We undertook this study to
      determine histological changes (inflammation, fibrosis and new vessel formation)
      in the peritoneum of Wistar rats after the application of physiological solution
      or DDAC. METHODS: The minimum inhibitory concentration (MIC) of DDAC for E. coli
      (512 MUg/ml) and E. faecalis (128 MUg/ml) was determined. Sixty-three Wistar rats
      weighing 200 +/- 20 g were studied. They were divided into three groups: control:
      7 rats were instilled with 3 ml of physiological solution in peritoneal cavity;
      groups 1 and 2 were instilled with 3 ml of MIC for E. coli and E. faecalis,
      respectively. These groups were divided into four subgroups of seven animals. In
      every rat, 1 cm(2) of peritoneum was obtained at 2, 7, 14, and 21 days for
      histological study with hematoxylin-eosin. Ten fields were evaluated. The data
      obtained were analyzed with the Mann-Whitney test. RESULTS: There were no
      significant differences in inflammation, fibrosis and new vessel formation with
      the physiological solution vs. DDAC at 2, 7, 14, and 21 days (p >0.05), except
      for inflammation at 2 days in group 2 (p = 0.026), which remitted. CONCLUSIONS:
      There was no significant difference in changes in rat peritoneum after
      physiological solution or DDAC application.

PMID- 22380994
TI  - Latencies obtained of the somatosensory evoked potentials of the median and
      tibial nerve in rhesus monkey undergoing intrauterine laminectomy to simulate
      myelomeningocele.
AB  - BACKGROUND: Somatosensory evoked potentials (SSEP) have been described as
      excellent indicators of the degree of medullar injury in degenerative and
      metabolic diseases of the central nervous system (CNS). The prevalence of neural
      tube defects (NTD) is 6 cases/10,000 live newborns worldwide. It is thought that
      genetic as well as environmental factors contribute to the etiology of NTD. The
      objective of this study was to analyze and compare the latencies obtained by
      means of SSEP in a clinically healthy monkey vs. rhesus monkeys with intrauterine
      surgery in order to simulate surgically the neural tube defect (myelomengocele)
      by performing an intrauterine laminectomy and in which later the defect was
      corrected. METHODS: This study was performed using three non-human primates of
      the Macaca mulatta species. There were practice intrauterine surgeries in two
      monkeys to simulate the neurological defect produced by myelomeningocele, using
      the third monkey as control. For statistical methodology four monkeys were used.
      They were born by natural birth without any surgical manipulation. With the
      cesarean-obtained products, stimulation was performed of the tibial and median
      nerve. RESULTS: We observed that the hind limbs were the most affected, in
      particular, the left afferent of the monkey. The spinal cord was exposed to
      amniotic fluid, and there were no significant differences in the forelimbs.
      CONCLUSIONS: The use of SSEP provides valuable information regarding preservation
      of sensorial functions in a variety of experimental neurological abnormalities.

PMID- 22380995
TI  - Vanek's polyp or inflammatory fibroid polyp. Case report and review of the
      literature.
AB  - BACKGROUND: Intussusception in an adult must make us suspect the presence of a
      tumor (benign or potentially dangerous) as the most frequent cause. Accurate
      diagnosis is of great importance in order to provide appropriate treatment and
      improve patient prognosis. CLINICAL CASE: We report the case of a 42-year-old
      male with abdominal pain. We performed a CT and found a small bowel
      intussusception. Definitive diagnosis according to the surgical specimen was
      inflammatory fibroid polyp (Vanek's polyp). CONCLUSIONS: Vanek's polyp is a
      benign lesion that occurs most frequently in the stomach and secondarily in the
      small bowel. Generally, it is uncommon, and its etiology is not completely known.
      Accurate diagnosis is done with immunohistochemistry. Because of the consequences
      that depend on the size and location of the lesion, it may be considered a
      malignant lesion. Treatment is resection.

PMID- 22380996
TI  - Management of pseudoaneurysm of the splenic artery: report of two cases.
AB  - BACKGROUND: Splenic pseudoaneurysm is an uncommon disease. It occurs as a
      consequence of injury to the vascular wall, mostly inflammatory. The main symptom
      is gastrointestinal bleeding. The objective of this paper is to present the case
      of two patients with splenic pseudoaneurysm. CASE REPORTS: The first case we
      present is a 26-year-old male with a history of idiopatic pancreatitis,
      pancreatic abscess and colonic fistula 3 years prior. The second case is a 20
      year-old male with a history of chronic kidney disease with peritoneal dialysis
      interrupted due to fungal (Candida albicans) peritonitis. Both patients presented
      with signs of lower gastrointestinal bleeding. Endoscopic examinations (upper
      endoscopy and colonoscopy) were inconclusive. Tomographic studies showed the
      lesion. Arteriography with embolization was performed and was satisfactory in one
      case and partially satisfactory in the other case. Surgery was done with proximal
      and distal ligation of the lesion with splenectomy. Postoperative evolution was
      satisfactory. During the follow-up for 6 and 12 months, neither patient has
      presented signs of recurrent bleeding. CONCLUSIONS: This is a very rare lesion
      usually presenting after a history of pancreatitis or abdominal trauma. This
      lesion must be ruled out in patients with obscure gastrointestinal bleeding.
      Arteriography with embolization is the best diagnostic and probably therapeutic
      procedure. Surgery is warranted for hemodynamically unstable patients,
      embolization failure or rebleeding.

PMID- 22380997
TI  - Adult intussusception with perforation and secondary peritonitis. Case report.
AB  - BACKGROUND: Intussuception is an uncommon condition in adults. It is usually
      secondary to an organic lesion that may be malignant. The most common clinical
      presentation is as a partial bowel obstruction that requires surgical management.
      Preoperative diagnosis remains difficult; therefore, this paper presents a case
      report and a brief review of adult intussusception. CLINICAL CASE: We present the
      case of a 24-year-old female with a 36-h evolution of lower abdominal pain with
      nausea, vomiting and diarrhea and a previous episode 8 days earlier.
      Pneumoperitoneum was observed on chest x-ray and surgery was decided upon.
      Peritonitis due to ileoileal intussusception was found, caused by an inflammatory
      fibroid polyp with microperforations. Small bowel resection with end-to-end
      anastomosis was performed and the patient had an uneventful recovery.
      CONCLUSIONS: Adult intussusception is an infrequent condition with nonspecific
      symptoms such as pain, nausea and vomiting. With more frequent use of tomography
      in patients with abdominal pain, correct diagnosis can be achieved. Treatment
      requires resection of the involved bowel without attempted reduction.

PMID- 22380998
TI  - Gliomatosis peritonei: recurrence, treatment and surveillance.
AB  - BACKGROUND: Gliomatosis peritonei is the metastatic implantation of mature glial
      tissue within the peritoneal cavity of patients with ovarian teratomas. There is
      no clear guidance for how long these patients should be followed up. CLINICAL
      CASE: We report the follow-up imaging findings of a 33-year-old female with
      abdominal distension and abdominal pain and who was postoperatively diagnosed
      with immature ovarian teratoma with gliomatosis peritonei. CONCLUSIONS:
      Differentiation of peritoneal implants seems to be important for prognosis.
      Malignant transformations after several years cannot be excluded. Therefore, new
      studies will determine if it is necessary to create guidelines for the
      postsurgical monitoring of these patients.

PMID- 22380999
TI  - Leiomyosarcoma of the kidney: case report.
AB  - BACKGROUND: Renal sarcomas represent 1-2% of malignant kidney tumors in adults;
      50% of renal sarcomas are composed of leiomyosarcomas. These tumors generally
      arise from the renal capsule, smooth muscle tissue of the renal pelvis and
      intrarenal vessels. They are indistinguishable from other renal masses prior to
      surgery and are associated with an adverse prognosis. CLINICAL CASE: We report
      the case of a 58-year-old female with a clinical course characterized by
      asthenia, weakness, generalized attack to her health status and pain in the left
      renal fossa. Computed axial tomography was performed where a left retroperitoneal
      tumor was diagnosed. Left radical nephrectomy was performed. The histopathology
      report demonstrated leiomyosarcoma originating from the renal sinus vessels. The
      patient was successfully treated with adjuvant radiotherapy. CONCLUSIONS: Renal
      leiomyosarcomas usually have an aggressive biological behavior with poor
      prognosis, accounting for surgical treatment with wide resection associated with
      adjuvant chemotherapy and radiotherapy as the only therapeutic option.

PMID- 22381002
TI  - Solvent-responsive structural colored balloons.
AB  - The structural colored balloons (SCBs) consisting of polymer microcapsules showed
      several structural colors developed by optical thin-layer interference. The SCBs
      were prepared using a mixture of low- and high-molecular-weight polystyrene to
      give solvent responsiveness. When the surrounding solvent was transferred from
      water to the acetone/water mixture using a flow cell, the SCBs swelled at first
      and shrunk subsequently. The gradual color change of the SCBs was observed along
      with the size change. The color change accompanying the size change was
      successfully reproduced by assuming that the total amount of polymer in the thin
      film does not change. The swelling rate was rationalized by the diffusion of
      solvent through the shell polystyrene film to the inside of the balloons.

PMID- 22381000
TI  - Practice guidelines for the management of low back pain. Consensus Group of
      Practice Parameters to Manage Low Back Pain.
AB  - It has been documented that pain in its diverse modalities is the most common
      cause of medical attention. In Mexico, an increase in its frequency has promoted
      its consideration in several health programs. On the other hand, inadequate pain
      management will cause severe physical, psychoaffective, and socioeconomic
      repercussions for patients, families, and public health services. Despite this
      panorama, there has not been an agreement to establish better diagnostic and
      therapeutic methods for the management of chronic pain. A consensus group was
      reunited and was integrated by medical experts from private and public
      institutions and from various states of the Mexican Republic. To assure the
      development of these practice guidelines, these experts had experience in the
      assessment and treatment of conditions causing pain. With the guidelines used by
      other consensus groups, meetings were held to analyze and discuss published
      literary evidence for the management of low back pain. The recommendations were
      classified according to their methodological strength. As a result of this
      meeting, consensus recommendations were based on evidence and operational
      conclusions of such proactive educational plans, institutional policies and
      diagnostic recommendations for pharmacological and nonpharmacological treatment
      in order for Mexican physicians to provide a better therapeutic approach to low
      back pain.

PMID- 22381003
TI  - High-definition fiber tracking for assessment of neurological deficit in a case
      of traumatic brain injury: finding, visualizing, and interpreting small sites of
      damage.
AB  - For patients with traumatic brain injury (TBI), current clinical imaging methods
      generally do not provide highly detailed information about the location of axonal
      injury, severity of injury, or expected recovery. In a case of severe TBI, the
      authors applied a novel high-definition fiber tracking (HDFT) to directly
      visualize and quantify the degree of axonal fiber damage and predict functional
      deficits due to traumatic axonal injury and loss of cortical projections.   This
      32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an
      area of hemorrhage in the basal ganglia with mass effect, but no specific
      information on the location of axonal injury could be obtained from these
      studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed
      motor weaknesses of the left extremities. Four months postinjury, 257-direction
      diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree
      of axonal damage in the motor pathway and quantify asymmetries in the left and
      right axonal pathways. High-definition fiber tracking was used to follow
      corticospinal and corona radiata pathways from the cortical surface to the
      midbrain and quantify projections from motor areas. Axonal damage was then
      localized by assessing the number of descending fibers at the level of the
      cortex, internal capsule, and midbrain. The motor deficit apparent in the
      clinical examinations correlated with the axonal losses visualized using HDFT.
      Fiber loss estimates at 4 months postinjury accurately predicted the nature of
      the motor deficits (severe, focal left-hand weakness) when other standard
      clinical imaging modalities did not. A repeat scan at 10 months postinjury, when
      edema and hemorrhage had receded, replicated the fiber loss.   Using HDFT, the
      authors accurately identified the presence and location of damage to the
      underlying white matter in this patient with TBI. Detailed information of injury
      provided by this novel technique holds future potential for precise neuroimaging
      assessment of TBI.

PMID- 22381004
TI  - Expected frequency of use and proficiency of core surgical skills in entry-level
      veterinary practice: 2009 ACVS core surgical skills diplomate survey results.
AB  - OBJECTIVES: ACVS Diplomates were surveyed to identify a complete list of core
      surgical skills, determine the expected frequency of use of these skills, and
      ascertain the level of skills proficiency expected of entry-level practicing
      veterinarians. STUDY DESIGN: Internet-based survey. SAMPLE POPULATION: Randomly
      chosen ACVS Diplomates (n = 750). METHODS: Rating scale items were used to
      construct the main portion of the survey with 26 skills that were scored by
      participants based on rankings of proficiency expected of entry-level
      veterinarians, as well as expected frequency of use of these skills. Additional
      demographic questions were included to gather information regarding gender,
      practice type, year of veterinary school, year of ACVS membership, job
      description, primary surgical discipline, practice location, average number of
      procedures performed on a weekly basis, and number of new graduates mentored in
      the last 5 years. RESULTS: Of 337 Diplomates (44.9%) who responded to the survey,
      >60% expected entry-level graduates to have good skills with minimal supervision
      or complete skills for 21 of the 26 skills categories listed. More than 60% of
      respondents ranked 7 skills with a lower frequency score (seldom or occasionally
      use). Orthopedic instrument handling and fixation skills as well as
      electrosurgical and laser skills received some of the lowest expected proficiency
      and frequency rankings. No additional skills categories were identified in the
      open-ended survey questions. CONCLUSIONS: A complete list of core surgical skills
      was identified. There was broad consensus between boarded surgeons irrespective
      of their practice type, experience, or discipline for ranked proficiency and
      frequency scores among the core surgical skills expected of entry-level
      veterinarians.

PMID- 22381005
TI  - Antihyperalgesic activity of the methanol extract and some constituents obtained
      from Polygala cyparissias (Polygalaceae).
AB  - Polygala cyparissias, used in folk medicine as an anaesthetic, has already
      demonstrated antinociceptive activity against acute pain. In this study, we
      investigated the antihyperalgesic activity of the P. cyparissias methanol extract
      (PCME) from which the following compounds were isolated: alpha-spinasterol (PC1),
      1,3-dihydroxy-7-methoxyxanthone (PC2), 1,7-dihydroxy-2,3-methylenedioxyxanthone
      (PC3) and 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (PC4). The antihyperalgesic
      effect was evaluated using experimental models of persistent pain induced by
      carrageenan, lipopolysaccharide (LPS), Freund's Complete Adjuvant (CFA), PGE(2)
      or epinephrine. The partial ligation of the sciatic nerve (PLSN) model was also
      used. In inflammatory hyperalgesia induced by carrageenan, LPS, CFA or PGE(2),
      the inhibition values obtained with the PCME treatment were 68 +/- 3%, 89 +/- 5%,
      43 +/- 3% and 40 +/- 4%, respectively. In epinephrine-induced hyperalgesia, the
      extract was effective, reducing 99 +/- 11% of response frequency, while in PLSN,
      54 +/- 4% of inhibition was obtained. These results allow to suggest that the
      antihyperalgesic activity of PCME is, at least in part, related to its capability
      to inhibit the hypersensitization induced by pro-inflammatory mediators, such as
      LPS, carrageenan and CFA, without interfering with locomotor activity or motor
      performance. Furthermore, compounds PC1, PC3 and PC4 inhibited the carrageenan
      induced hyperalgesia with inhibition of 42 +/- 6%, 48 +/- 5% and 64 +/- 4%,
      respectively. In summary, our data demonstrate that PCME has relevant
      antihyperalgesic activity and that the isolated PC1, PC3 and PC4 seem to be
      responsible, at least in part, for this important effect.

PMID- 22381006
TI  - Polymorphism of collagen triple helix revealed by 19F NMR of model peptide [Pro
      4(R)-hydroxyprolyl-Gly]3-[Pro-4(R)-fluoroprolyl-Gly]-[Pro-4(R)-hydroxyprolyl
      Gly]3.
AB  - We have characterized various structures of (Pro-Hyp(R)-Gly)(3)-Pro-fPro(R)-Gly
      (Pro-Hyp(R)-Gly)(3) in the process of cis-trans isomerization and helix-coil
      transition by exploiting the sole (19)F NMR probe in 4(R)-fluoroproline
      (fPro(R)). Around the transition temperature (T(m)), we detected a species with a
      triple helical structure distinct from the ordinary one concerning the alignment
      of three strands. The (19)F-(19)F exchange spectroscopy showed that this
      misaligned and that the ordinary triple helices were interchangeable only
      indirectly via an extended monomer strand with all-trans peptide bonds at Pro
      fPro(R), Pro-Hyp(R), and Gly-Pro in the central segment. This finding
      demonstrates that the helix-coil transition of collagen peptides is not described
      with a simple two-state model. We thus elaborated a scheme for the transition
      mechanism of (Pro-Hyp(R)-Gly)(n) that the most extended monomer strand can be the
      sole source both to the misaligned and correctly folded triple-helices. The
      staggered ends could help misaligned triple helices to self-assemble to higher
      order structures. We have also discussed the possible relationship between the
      misaligned triple helix accumulating maximally at T(m) and the kinetic hysteresis
      associated with the helix-coil transition of collagen.

PMID- 22381007
TI  - HDA19 is required for the repression of salicylic acid biosynthesis and salicylic
      acid-mediated defense responses in Arabidopsis.
AB  - To cope with a lifetime of exposure to a variety of pathogens, plants have
      developed exquisite and refined defense mechanisms that vary depending on the
      type of attacking pathogen. Defense-associated transcriptional reprogramming is a
      central part of plant defense mechanisms. Chromatin modification has recently
      been shown to be another layer of regulation for plant defense mechanisms. Here,
      we show that the RPD3/HDA1-class histone deacetylase HDA19 is involved in the
      repression of salicylic acid (SA)-mediated defense responses in Arabidopsis. Loss
      of HDA19 activity increased SA content and increased the expression of a group of
      genes required for accumulation of SA as well as pathogenesis related (PR) genes,
      resulting in enhanced resistance to Pseudomonas syringae. We found that HDA19
      directly associates with and deacetylates histones at the PR1 and PR2 promoters.
      Thus, our study shows that HDA19, by modifying chromatin to a repressive state,
      ensures low basal expression of defense genes, such as PR1, under unchallenged
      conditions, as well as their proper induction without overstimulation during
      defense responses to pathogen attacks. Thus, the role of HDA19 might be critical
      in preventing unnecessary activation and self-destructive overstimulation of
      defense responses, allowing successful growth and development.

PMID- 22381008
TI  - Casein micelles and their internal structure.
AB  - The internal structure of casein micelles was studied by calculating the small
      angle neutron and X-ray scattering and static light scattering spectrum (SANS,
      SAXS, SLS) as a function of the scattering contrast and composition. We predicted
      experimental SANS, SAXS, SLS spectra self consistently using independently
      determined parameters for composition size, polydispersity, density and
      voluminosity. The internal structure of the casein micelles, i.e. how the various
      components are distributed within the casein micelle, was modeled according to
      three different models advocated in the literature; i.e. the classical sub
      micelle model, the nanocluster model and the dual binding model. In this paper we
      present the essential features of these models and combine new and old
      experimental SANS, SAXS, SLS and DLS scattering data with new calculations that
      predict the spectra. Further evidence on micellar substructure was obtained by
      internally cross linking the casein micelles using transglutaminase, which led to
      casein nanogel particles. In contrast to native casein micelles, the nanogel
      particles were stable in 6M urea and after sequestering the calcium using
      trisodium citrate. The changed scattering properties were again predicted self
      consistently. An important result is that the radius of gyration is independent
      of contrast, indicating that the mass distribution within a casein micelle is
      homogeneous. Experimental contrast is predicted quite well leading to a match
      point at a D(2)O volume fraction of 0.41 ratio in SANS. Using SANS and SAXS model
      calculations it is concluded that only the nanocluster model is capable of
      accounting for the experimental scattering contrast variation data. All features
      and trends are predicted self consistently, among which the 'famous' shoulder at
      a wave vector value Q=0.35 nm(-1) In the nanocluster model, the casein micelle is
      considered as a (homogeneous) matrix of caseins in which the colloidal calcium
      phosphate (CCP) nanoclusters are dispersed as very small (about 2 nm) "cherry
      stones" at an average distance of 18.6 nm. Attached to the surface of the
      nanoclusters are the centers of phosphorylation (3-5 nearby phosphorylated amino
      acid residues) of the caseins. The tails of the caseins, much larger than the CCP
      clusters, then associate to form a protein matrix, which can be viewed as polymer
      mesh with density fluctuations at the 2 nm scale. The association of the tails is
      driven by a collection of weak interactions. We explicitly use weak interactions
      as a collective term for hydrophobic interactions, hydrogen bonding, ion bonding,
      weak electrostatic Van der Waals attraction and other factors (but not the strong
      calcium phosphate interaction) leading to self association. The association is
      highly cooperative and originates in the weak interactions. It is the
      cooperativety that leads to a stable casein micelle. Invariably, kappa-casein is
      thought to limit the process of self association leading to stabilization of the
      native casein micelle.

PMID- 22381009
TI  - The zone-based approach for selection of tympanoplasty technique.
AB  - At the outset of surgery, the extent of a tympanic membrane defect is judged
      including any additional loss of area that may result from disease extirpation or
      removal of the mucocutaneous junction. There are, three tiers of complexity when
      deciding upon which technique should be used for repair. Limited central
      perforations are defects amenable to a standard underlay technique. The Zone
      Based Approach is applied for marginal perforations whereby the specific
      technique is selected based on the zone of the defect. The zones and specific
      techniques are detailed. There are however, still a significant number of
      patients who have scarce residual tympanic membrane, or keratin matrix adherently
      involving the undersurface requiring sacrifice. These situations prove poor for
      either standard underlay or the zone based techniques. The total tympanic
      membrane reconstruction (TT MR) technique was developed specifically to avoid
      these complications as well as facilitate extirpation of the more extensive
      inflammatory and neoplastic pathologies commonly encountered, yet still amenable
      to intact canal wall mastoidectomy approaches.

PMID- 22381010
TI  - [The long-term results of treatment of Meniere's disease with intratympanic
      injections of gentamicin].
AB  - OBJECTIVE: To estimate the results of treatment of Meniere's disease with
      intratympanic injections of gentamicin. MATERIAL: 37 patients with defined,
      pharmacological treatment resistant Meniere's disease treated in Department of
      Otolaryngology and Laryngological Oncology of University of Medical Sciences in
      Poznan with intratympanic injections of gentamicin from 2001 to 2010 year.
      METHODS: Patients were injected intratympanic with 0.3 ml (12 mg) of gentamicin
      once or few times with 7 days or longer breaks and a number of injections
      depended on the reaction of the inner ear. We estimated the patients' subjective
      feelings and results of equilibrium and hearing organ examination in early (3
      months) and late (2 years) period after treatment. RESULTS: Complete control of
      vertigo (class A) was achieved in 84.6%, and complete and essential control
      (class A and B) in 96.1%. Hearing deterioration usually mild or moderate was
      observed directly after treatment in 16.2% and after 2 years in 23% patients. The
      results of pure tone audiometry showed deterioration of hearing in 16.2% (early)
      and 26.9% (late). In 1 patient hearing deterioration was essential. CONCLUSIONS:
      Intratympanic injections of gentamicin are effective and not troublesome method
      of treatment of pharmacological treatment resistant Meniere's disease. In most of
      patients hearing can be preserved, but they should be always informed about
      possible risk of hearing deterioration. The number of injections and breaks
      between them depends on the effect of therapy and of expectations of patients.

PMID- 22381011
TI  - [The evaluation of apoptosis in peripheral blood lymphocytes in laryngeal cancer
      patients].
AB  - The laryngeal cancer is the most often cancer among others in head and neck
      region. It occurs mostly among 55 and 69. Its development depends on
      immunological state of the body. Vitality of the immunological system cells was
      considered due to growth, treatment sensitivity and prognosis of some neoplasms.
      The aim of this work were estimation and comparison the phenomenon of lymphocytes
      T and B apoptosis in laryngeal cancer patients treated with surgery and
      radiotherapy. MATERIAL AND METHODS: The material were 30 patients hospitalized in
      The Department of Otolaryngology Medical University of Lublin. They all were
      treated with surgery or surgery and radiotherapy. Apoptosis was estimated on
      different stages of the treatment process. All samples were examined with the
      flow cytometry method. The control group were 21 patients hospitalized because of
      the suspicion of the apnea syndrome, which wasn't confirmed with polysomnographic
      examination. RESULTS: Results of this study show significantly increasing
      percentage of peripheral blood apoptotic B (CD19+) cells caused by surgical
      treatment. The results considering radiotherapy showed different influence on the
      phenomenon of immunological cells apoptosis, still those results weren't
      significant. CONCLUSIONS: The surgical treatment causes increased amount of
      apoptotic peripheral blood lymphocytes.

PMID- 22381012
TI  - [Laryngopharyngeal Reflux (LPR) in patients with persistent hoarseness].
AB  - INTRODUCTION: In 2006 The Global Consensus Group in Montreal pointed out that
      chronic laryngitis is highly associated with gastroesophageal reflux disease
      (GERD). AIM OF THE STUDY: To evaluate the frequency of LPR in a selected group of
      patients with chronic hoarseness. We were also interested in assessment of the
      relationship between Reflux Symptoms Index (RSI) scores, Ryan scores from the
      pharyngeal pH monitoring and the morphological changes in the larynx according to
      Reflux Findings Score (RFS). In addition, we wanted to assess the frequency of
      various clinical symptoms included in the RSI questionnaire among patients with
      LPR. MATERIALS AND METHODS: 42 patients from an outpatient ENT clinic with
      chronic hoarseness and RSI >= 13. All subjects underwent pharyngeal pH monitoring
      with the Dx-pH System Restech TM and laryngoscopy. RESULTS: Among 42 patients
      with chronic hoarseness, LPR was confirmed in 35 patients (83.33%). In 7 subjects
      pharyngeal pH monitoring was normal. Among all patients with confirmed LPR, only
      5 out of 8 elements of RFS laryngoscopic changes were observed. The most frequent
      inflammatory changes noticed included erythema of the arytenoids and
      interarytenoid regions (posterior laryngitis). These findings were found in 30
      out of 35 patients with LPR. Median value of RFS in patients with LPR was 4.45,
      which is lower than the cut off value of 7 necessary for recognition of LPR.
      There is statistically significant positive correlation between Ryan scores and
      the RFS scale results (correlation coefficient 0.91, p<0.001). CONCLUSIONS:
      Pharyngeal pH monitoring confirmed LPR in 83.33% selected group of patients with
      chronic hoarseness and RSI >= 13. Isolated erythema of arytenoid and
      interarytenoid region was the most frequent inflammatory abnormality found in the
      larynx. RFS values below 7 do not exclude the diagnosis of LPR. We can use RFS
      scales as a prognostic test of severity of LPR - due to statistically significant
      positive correlation between Ryan score and RFS values. The use of RSI scale
      revealed that the most frequent symptom among patient with LPR was throat
      clearing followed by hoarseness.

PMID- 22381013
TI  - [Orbital tumors in material of Department of Head and Neck Surgery and
      Oncological Laryngology of Greater Poland Cancer Center 2007-2010].
AB  - INTRODUCTION: Tumors of the orbit are diagnosed sporadically. Based on the tumor
      registry of the American Cancer Society the incidence of tumors of the orbit is
      assessed at fewer than 1 per 100 000 persons. Tumors of the orbit can be divided
      into three groups: primary tumors, tumors penetrating the orbit from neighboring
      structures, and tumors that are metastases of malignant cancers from distant
      organs. AIM OF THE STUDY: To present the results of treatment of patients with
      tumors of the orbit treated in the Head and Neck Surgery and Laryngological
      Oncology Ward of the Greater Poland Cancer Centre in Poznan during 2007-2010.
      MATERIAL AND METHODS: The study group consisted of 26 patients surgically treated
      during 2007-2010 in the Head and Neck Surgery and Laryngological Oncology Ward of
      the Greater Poland Cancer Centre in Poznan. RESULTS: In the postoperative
      histopathological examination 18 patients (69%) were diagnosed with malignant
      tumors, 7 patients (27%) with non-malignant tumor and 1 patient (4%) with
      inflammatory lesion. Among malignant tumors the most frequent was basal cell
      carcinoma, diagnosed in 7 patients (27%). When removing the tumors of the orbit 4
      types of operation were performed: lateral orbitotomy, superior orbitotomy, eye
      enucleation, and exenteration of the orbit. In 3 patients (12%) cancer
      recurrences occurred. All patients with recurrences underwent reoperation. In a
      patient with an extensive recurrence of squamous cell carcinoma the surgery was
      not radical and the patient died during palliative chemotherapy. CONCLUSIONS:
      Patients with tumors of the orbit should be treated operatively in appropriately
      prepared centers. In our material the confirmation of this thesis is the group of
      patients with recurrences of basal cell carcinoma, operated on many times in the
      past, who due to the extent of the cancerous process had to have the seeing eye
      removed. In the case of malignant cancers of the orbit an interdisciplinary
      approach to the problem and the assurance of psychological care for patients who
      have lost an orbit are essential.

PMID- 22381014
TI  - [The parotid glands neoplasms in material of the otolaryngology clinical ward of
      4(th) Military Clinical Hospital with the Polyclinic in Wroclaw in the years 1992
      2010].
AB  - AIM: The aim of the study is the analyses of parotid glands neoplasms on 105
      patients who underwent surgery at the Otolaryngology Clinical Ward of 4(th)
      Military Clinical Hospital with the Policlinic in Wroclaw in the years 1992-2010.
      MATERIAL AND METHODS: In the group of patients with parotid glands tumor there
      were 52 women and 53 men. The following data: age, sex, time between appearing
      first symptoms and operation, the kind of the executed operation and the result
      of histopathological examination were taken into account in this study. RESULTS
      AND CONCLUSIONS: The most common of tumors are benign neoplasms (88%), the
      malignant ones are in 12% of patients. The most frequent tumor is pleomorphic
      adenoma (53%), the second one is lympho-adenoma (26%). In parotid gland tumors
      are often located on the left side (60%). Authors noticed significant development
      of the quantity operated parotid salivary gland tumors in the last three years.

PMID- 22381015
TI  - [Long term results of partial laryngectomies in patients suffering from laryngeal
      cancer].
AB  - AIM: The aim of the study was to evaluate the results of partial laryngectomies
      in patients with laryngeal cancer treated in the 2(nd) Clinical Department of
      Laryngology SUM in Zabrze in the years 1990-2000. MATERIALS AND METHODS:
      Retrospective clinical material includes 209 patients in whom surgery was a
      primary treatment method. No distant metastases (M1) or another malignant cancer
      were found. The group consisted of 20 (10%) women and 189 (90%) men. The mean age
      was - 51.2 years. The stage of the neoplasm progression was defined as T1 in 91
      patients (44%), T2 in 109 patients (52%). In other 9 patients (4%) the
      progression stage was T3 and T4. Clinical examination in 191 patients (91%) did
      not show enlarged lymph nodes in the area of head and neck (N0). In the group of
      remaining 18 patients (9%) the node progression was found to be N1-N3. In all 209
      patients the squamous cell carcinoma of various stage of malignancy (G1-G3) was
      found in preoperative histopathological tests, out of which five cases were of
      papillary squamous cell carcinoma. The most common operation in the analyzed
      group was a chordectomy - 83 surgeries (40%), followed by 38 (18%) vertical
      partial laryngectomies, 28 (13%) horizontal glottis surgeries, 19 (9%) frontal
      lateral and frontal-anterior operations, and supracricoid operations with a
      reconstruction of CHEP and CHP type, a total of 20 operations (9%). Other types
      of partial operations were performed less commonly. In 79 patients (38%) partial
      laryngectomy was complemented with a nodal operation, while cervical lymph nodes
      were not removed in 130 patients (62%). In 19 cases (9%) the metastases of
      squamous cell carcinoma to regional lymph nodes were confirmed in postoperative
      material. 82 patients of the study group (39%) underwent radiotherapy. The median
      of the observation period was 9 years. Local recurrence, nodal recurrence and
      distant metastasis are rated as treatment failure. Treatment effectiveness was
      evaluated with relation to local control, overall survival, disease-free survival
      and cause specific survival. All the aforementioned parameters were analyzed with
      the method of updated percentages. The level of statistical significance was
      assumed to be p <= 0.05. RESULTS: The updated 5-year and 10-year percentage of
      overall survivals was respectively 75% and 63%. The updated 5-year and 10-year
      percentage of cancer specific survivals was 85% and 79%, respectively. The
      updated 5-year and 10-year percentage of disease-free survivals was 72% and 56%,
      respectively. The percentage of 5-year and 10 year local controls was 86% and
      79%, respectively.

PMID- 22381016
TI  - [Our experience in the use of anterolateral thigh flap for reconstruction of the
      head and neck neoplasms].
AB  - INTRODUCTION: Free flaps with vascular anastomosis have been widely used in
      clinical practice for more than 30 years. They are standard in reconstructive
      surgery following extensive resections caused by neoplasms of the head and neck.
      The anterolateral thigh flap (ALT) constitutes very good reconstructive material
      due to the long vascular pedicle, the appropriate diameter of vessels, the large
      skin island plane, and thickness depending on requirements. MATERIAL: The own
      material comprises 5 patients who have had extensive neoplastic infiltrations
      removed at different anatomic locations within the area of healthy tissue.
      RESULTS: Reconstructions have been conducted using a microvascular thigh flap
      (ALT). All of the operated patients are under constant supervision. The
      observation period ranges from 2 to 3 months. No recurrence of the neoplastic
      process or graft rejection has been observed in any of the patients.

PMID- 22381017
TI  - [Comparison of different deafening strategies based on ototoxic drugs on mouse
      animals model].
AB  - AIM OF THE STUDY: To compare safety, reliability and usefulness of two deafening
      protocols on animal mouse model, based on aminoglycosides exposure MATERIAL AND
      METHOD: Adults mice, Bulb/C, deafened with kanamycine 14 days treatment (group
      I), single kanamycin injection followed by etacrinic acid administration (group
      II) and control group. Hearing evaluation performed with ABR recordings on 6th
      day after drug exposure RESULTS: Both protocols were not able to guarantee
      complete ablation of the inner ear in tested animals. Although short deafening
      strategy was more effective (83.33% deaf mice) it was combined with high rate of
      mortality during general anesthesia for hearing evaluation. CONCLUSIONS: Variable
      outcomes in deafening mouse animal model implies the necessity of hearing
      evaluation every time prior to the pathophysiological as well as molecular
      studies. Mice exposed to severe oto- and nephrotoxic insult do not recover after
      anesthetic drug administration, thus harvesting inner ear tissues especially as
      the source of RNA should be performed immediately after ABR recordings.

PMID- 22381018
TI  - [Rare case of haemangioma of the pharynx].
AB  - The hemangioma is a benign tumour located mostly in the region of head and neck.
      It can appear at any age but especially it is diagnosed among children. The
      disease can be successfully treated with surgery, criotherapy, propranolol or
      endovascular procedures. The rare case of the 59-year-old, male patient with huge
      heamangioma of the pharynx was shown in this paper. The patient was mildly
      symptomatic - he neglected difficulty with swallowing or breathing and there was
      no pain. The only one complaint was experiencing a worsened hearing in the left
      ear. The patient was referred to the laryngologist with acute pharyngitis and
      with the suspicion of peritonsillar abscess. In the ENT examination apart from
      acute tonsillitis, the tumour of pharynx was diagnosed. Diagnostic puncture of
      the tumour showed blood. Ambulatory treatment with antibiotics was administered.
      The inflammation of pharynx was cured but the tumour remained. In the ENT
      department the patient underwent diagnostic process including CT of the head,
      angioCT of carotid arteries and consultation of vascular surgeon. The diagnosis
      was established and patient was referred for endovascular treatment. The outcome
      of the embolization of hemangioma resulted in reducing the tumour size and
      decreasing patient's symptoms. The epidemiology, diagnostic problems and therapy
      were described.

PMID- 22381019
TI  - Metallic foreign body in the neck: case report.
AB  - Penetrating neck injuries constitute 5-10% of all trauma cases. Such injuries are
      dangerous because of the high risk of injury to the vital structures in the neck
      and hence demand an immediate surgical exploration. We present a case of a
      penetrating injury of the neck caused by the broken metallic fragment of a saw.

PMID- 22381020
TI  - beta-cell dysfunction and the onset of type 2 diabetes.

PMID- 22381021
TI  - Gowers' sign as an indication of recovery from Guillain-Barre syndrome.

PMID- 22381022
TI  - Developmental and functional outcomes in children with a positive newborn screen
      for Krabbe disease: a pilot study of a phone-based interview surveillance
      technique.
AB  - OBJECTIVE: To assess the utility of a telephone-based interview system in
      providing ongoing monitoring of the developmental and functional status of
      children with both positive newborn screens for Krabbe disease and low
      galactocerebrosidase activity on confirmatory testing, and to determine whether
      this approach provides improved compliance with follow-up compared with formal
      neuropsychological testing. STUDY DESIGN: Infants with low galactocerebrosidase
      activity (as detected by the New York State newborn screening program) were
      eligible for this longitudinal prospective cohort study. Consenting families were
      interviewed by telephone at infant ages of 4, 8, 12, 18, and 24 months.
      Designated instruments were the Ages and Stages Questionnaires, the Clinical
      Linguistic and Auditory Milestone Scale, the Gross Motor Quotient, the Warner
      Initial Developmental Evaluation of Adaptive and Functional Skills 50, and the
      WeeFIM II 0-3 instrument. Assessments with the Bayley Scales of Infant and
      Toddler Development, Third Edition (Bayley III) were scheduled at age 12 and 24
      months. RESULTS: Seventeen patients were enrolled; 16 were assessed at age 12 and
      18 months, and 15 were assessed at age 24 months. Scores were within the normal
      range on all tests of developmental and functional status, with the exception of
      expressive language. Only 7 patients completed the Bayley Scales of Infant and
      Toddler Development, Third Edition assessments; all their scores were in the
      normal range. CONCLUSION: This telephone-based technique allows close monitoring
      of the developmental and functional status of children with a positive newborn
      screen for this neurometabolic disease, with special attention to detecting
      plateauing or regression of developmental milestones. Compliance is improved
      compared with formal neuropsychological testing.

PMID- 22381023
TI  - Physical comorbidity of migraine and other headaches in US adolescents.
AB  - OBJECTIVE: To examine the pattern and extent to which other physical conditions
      are comorbid with migraine and other headaches in youth in a representative
      sample of the US population. STUDY DESIGN: The National Comorbidity Survey
      Adolescent Supplement is a face-to-face survey of adolescents aged 13-18 years in
      the continental US. Sufficient information to assess the International Headache
      Society's criteria for migraine with and without aura over the past 12 months was
      available in the diagnostic module. A caretaker/parental self-administered report
      was used to assess a broad range of other physical conditions. The sample for
      these analyses was 6843 adolescents with systematic caretaker/parent reports.
      RESULTS: Adolescents with any headaches reported higher rates of other neurologic
      conditions, including epilepsy (OR, 2.02; 95% CI, 1.04-3.94), persistent
      nightmares (OR, 2.28; 95% CI, 1.34-3.87), and motion sickness (OR, 1.6; 95% CI,
      1.07-2.4), as well as abdominal complaints (OR, 2.36; 95% CI, 1.59-3.51). Asthma
      (OR, 2.22; 95% CI, 1.26-3.92) and seasonal allergies (OR, 1.66; 95% CI, 1.12
      2.48) were more common in adolescents with migraines than in adolescents with
      nonspecific headaches. CONCLUSION: Adolescent migraine is associated with
      inflammatory conditions such as asthma and seasonal allergies, as well as with
      epilepsy, persistent nightmares, and motion sickness. Our findings suggest that
      comorbid medical conditions should be evaluated comprehensively in determining
      treatment options in youth with headache. Such comorbidity also could be an
      important source of the clinical and etiologic heterogeneity in migraine.

PMID- 22381024
TI  - Role of carbohydrate modification in weight management among obese children: a
      randomized clinical trial.
AB  - OBJECTIVE: To compare the effectiveness and safety of carbohydrate (CHO)-modified
      diets with a standard portion-controlled (PC) diet in obese children. STUDY
      DESIGN: Obese children (n=102) aged 7-12 years were randomly assigned to a 3
      month intervention of a low-CHO (LC), reduced glycemic load (RGL), or standard PC
      diet, along with weekly dietary counseling and biweekly group exercise.
      Anthropometry, dietary adherence, and clinical measures were evaluated at
      baseline and 3, 6, and 12 months. Analyses applied intention-to-treat
      longitudinal mixed models. RESULTS: Eighty-five children (83%) completed the 12
      month assessment. Daily caloric intake decreased from baseline to all time points
      for all diet groups (P<.0001), although LC diet adherence was persistently lower
      (P<.0002). At 3 months, body mass index z score was lower in all diet groups (LC,
      -0.27 +/- 0.04; RGL, -0.20 +/- 0.04; PC, -0.21 +/- 0.04; P<.0001) and was
      maintained at 6 months, with similar results for waist circumference and percent
      body fat. At 12 months, participants in all diet groups had lower body mass index
      z scores than at baseline (LC, -0.21 +/- 0.04; RGL, -0.28 +/- 0.04; PC, -0.31 +/-
      0.04; P<.0001), and lower percent body fat, but no reductions in waist
      circumference were maintained. All diets demonstrated some improved clinical
      measures. CONCLUSION: Diets with modified CHO intake were as effective as a PC
      diet for weight management in obese children. However, the lower adherence to the
      LC diet suggests that this regimen is more difficult for children to follow,
      particularly in the long term.

PMID- 22381025
TI  - Insulin resistance and adiposity in relation to serum beta-carotene levels.
AB  - OBJECTIVE: To determine the effects of placebo vs an encapsulated supplement of
      fruit and vegetable juice concentrate (FVJC) on serum beta-carotene levels,
      insulin resistance, adiposity, and subclinical inflammation in boys. STUDY
      DESIGN: Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age
      range, 6-10 years) were studied. All participants received nutrition counseling
      and were randomized to receive FVJC or placebo capsules for 6 months. Total
      cholesterol, triglycerides, lipid corrected beta-carotene, serum retinol,
      glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to
      adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were
      measured before and after the 6-month intervention. Homeostasis model assessment
      insulin resistance (HOMA-IR), acute insulin response to intravenous glucose,
      along with abdominal fat mass (dual-energy x-ray absorptiometry) were also
      determined. RESULTS: Baseline beta-carotene concentrations correlated inversely
      with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P <= .01).
      FVJC intake increased beta-carotene concentrations (P <= .001) but did not
      influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 MUM
      was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA
      IR decreased after supplementation in the OW cohort, when adjusted for percent
      weight change (P = .014). The percent change in abdominal fat mass increased in
      the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS: A 6
      month supplementation with FVJC in the presence of nutritional counseling was
      associated with an increase in serum beta-carotene concentrations and a reduction
      in adiposity in conjunction with an improvement in insulin resistance in OW boys.

PMID- 22381026
TI  - Preclinical evaluation and molecular docking of 4-phenyl-1-Napthyl phenyl
      acetamide (4P1NPA) from Streptomyces sp. DPTB16 as a potent antifungal compound.
AB  - The incidence of fungal disease has increased dramatically over the past decades,
      mainly due to the emergence and transmission of antifungal resistance within the
      fungal pathogens. The present study investigates the use of novel antifungal
      compound 4-Phenyl-1-Napthyl Phenyl Acetamide (4P1NPA), isolated from marine
      Streptomyces sp. DPTB16 as a potent antifungal drug. The preclinical studies and
      molecular docking for 4P1NPA against Cytochrome P450 51 (CYP 51) were performed
      using in silico pharmacology and docking tools. The finding reveals the drug
      likeliness of 4P1NPA and satisfactory interaction of 4P1NPA with CYP 51. These
      results collectively evidence the use of 4P1NPA as a drug to treat fungal
      infections. On the whole, we highlight the findings of this research will be
      helpful to design 4P1NPA as novel antifungal drug to defend the emerging
      antifungal resistance.

PMID- 22381027
TI  - Atopic diseases by filaggrin mutations and birth year.
AB  - BACKGROUND: The prevalence of atopic disorders has increased in recent years. The
      pathogenesis is complex with genetic and environmental risk factors. Filaggrin
      loss-of-function mutations are common and associated with atopic disorders. We
      investigated whether the prevalence of filaggrin mutations increased in different
      birth cohorts in adults from the general population in Denmark. METHODS: Cross
      sectional questionnaire and filaggrin gene mutation (R501X and 2282del4) data
      from 3335 18- to 69-year-old adults were available for analyses. RESULTS: The
      effect of filaggrin mutations on the prevalence of atopic diseases, albeit not
      statistically significant, depended mostly on birth year for atopic dermatitis
      (AD). A nonsignificant increase in the prevalence of filaggrin mutations was
      noted across birth year groups reporting AD, with 12.9% in adults born in 1936
      1949 and 19.0% born in 1976-1988. CONCLUSIONS: If confirmed in other populations,
      the observed increase suggests that mutation carriers have been more susceptible
      to environmental changes accentuating the rise in AD prevalence.

PMID- 22381028
TI  - One-step synthesis and characterization of core-shell Fe@SiO2 nanocomposite for
      Cr (VI) reduction.
AB  - A facile one-step method was developed to fabricate mono-dispersed Fe
      nanoparticles (Fe NPs) coated with SiO(2) shell by aqueous reduction method
      combined with modified Stober method. Borohydride was acted not only as a
      reductant for iron salt but also as a catalyst for hydrolysis and
      polycondensation reaction of tetraethylorthosilicate (TEOS), and more
      importantly, there was no need to use surface primer for the generation of Fe NPs
      and catalyst NH(4)OH for SiO(2). Both the Fe NPs agglomeration and SiO(2) shell
      thickness can be controlled through the synthetic conditions. Lower potassium
      borohydride (KBH(4)) injection speed was preferable to assemble Fe NPs. The
      SiO(2) shell thickness increased gradually with the increase of TEOS amount.
      Under the condition of TEOS amount of 0.1mL and KBH(4) injection speed of
      5mL/min, 25nm single Fe NP was coated with SiO(2) shell with thickness of about
      9nm. The resulting nanoporous SiO(2) shell was proved to allow reactant to reach
      the Fe NPs while at the same time protect them from aggregation. The reactivity
      characterization of the SiO(2)-coated Fe nanoparticles (Fe@SiO(2)) showed that
      both TEOS concentration and KBH(4) injection speed had effect on Cr (VI)
      degradation ability. The highest removal capacity of Fe@SiO(2) can reach
      467mgCr/gFe at an initial Cr (VI) concentration of 70mg/L under pH 6.0+/-0.1. XPS
      and TEM results showed that Cr (VI) was converted to nontoxic Cr (III) and the
      reaction product was completely adsorbed to SiO(2) shell.

PMID- 22381029
TI  - A high-resolution dialysis technique for rapid determination of dissolved
      reactive phosphate and ferrous iron in pore water of sediments.
AB  - Characterization of pore water chemistry necessitates measurements of the
      chemical components at a high spatial resolution due to the heterogeneous nature
      of sediments. In this study, a novel high-resolution dialysis technique was
      developed for rapid sampling of dissolved reactive phosphate (DRP) and ferrous
      iron (Fe) in pore water at a vertical resolution of 2mm. This technique employed
      a mini dialysis device (peeper) with a deployment time of 2 days in sediments for
      equilibration. Operational procedures following retrieval of the peeper include
      in situ freezing of the pore water samples through spraying commercial carbon
      dioxide snow, frozen storage of the pore water samples, and quick analysis of
      chemicals in pore water samples using 384-well microplate photometric methods.
      The sample consumption for each parameter can be minimized to 6MUL, which allowed
      simultaneous determination of DRP and ferrous iron in a peeper device. Laboratory
      tests showed that the technique was robust enough for the in situ measurements.
      Field deployment was subsequently performed in three sites of a shallow,
      eutrophic bay in Lake Taihu of China. Simultaneous determination of DRP and
      ferrous Fe in all the sites demonstrated a similar behavior of both chemicals in
      the pore water profiles, verifying the control of P mobilization by Fe in
      sediments.

PMID- 22381030
TI  - Trastuzumab-induced cardiotoxicity: the role of two-dimensional myocardial strain
      imaging in diagnosis and management.
AB  - A 45-year-old female breast cancer patient developed heart failure during
      adjuvant trastuzumab therapy. Her initial left ventricular ejection fraction
      (LVEF) was 39% and corresponding global longitudinal and circumferential systolic
      strain measurements were also significantly reduced. Trastuzumab was ceased and
      supportive cardiac therapy commenced. The ensuing LVEF and systolic strain
      measurements showed consistent improvement so that trastuzumab was recommenced
      (while supportive cardiac therapy continued). At this point, reduced
      circumferential systolic strain with preserved LVEF was observed. Subsequent
      echocardiograms revealed further reductions in circumferential and longitudinal
      systolic strain without reductions in LVEF.

PMID- 22381031
TI  - Seizure activity in dogs is associated with enhanced TIMP-2 expression of
      microglia.
AB  - In the pathogenesis of epilepsy aberrant synaptic plasticity plays an important
      role. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are
      responsible for nervous tissue remodelling resulting in synaptic plasticity in
      the central nervous system (CNS) and might therefore be crucially involved in
      epileptogenesis. To assess the potential pathogenetic role of microglial MMPs and
      TIMPs in seizure induction, twenty-four dogs suffering from different
      intracranial diseases with and without seizure activity were comparatively
      examined. Microglial cells were isolated by density gradient centrifugation and
      their expression profiles of MMP-2, MMP-9, MMP-12, MMP-13, MMP-14, TIMP-1, TIMP
      2, and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) were
      examined via quantitative real-time PCR (qPCR). Interestingly, a significant up
      regulation of TIMP-2 expression was found for the first time in dogs suffering
      from seizures. In conclusion, microglial TIMP expression might be involved in
      seizure generation.

PMID- 22381032
TI  - American origin of Cupriavidus bacteria associated with invasive Mimosa legumes
      in the Philippines.
AB  - To identify the origins of Cupriavidus nodule symbionts associated with two
      invasive Mimosa species in the Philippines, 22 isolates were sequenced for
      portions of three chromosomal genes and two symbiotic plasmid loci. Eleven
      isolates were identical at all gene loci (2713 bp) to a lineage found in Central
      America. Four other Philippine isolates were identical to a second Cupriavidus
      lineage distributed both in Central America and in the Caribbean. None of the
      remaining Philippine strains had more than 0.6% sequence divergence from American
      Cupriavidus lineages. These results imply that the Philippine population was
      founded by multiple introductions from the native range of their Mimosa hosts.

PMID- 22381033
TI  - Subclinical hypothyroidism and the heart: the beat goes on.

PMID- 22381035
TI  - Shape deformation and recovery of multilayer microcapsules after being squeezed
      through a microchannel.
AB  - The deformation and recovery behaviors of multilayer microcapsules were
      investigated after being forced to flow through a microchannel. The microchannel
      device with a constriction (5.7 MUm in depth) in the middle was designed, and the
      multilayer microcapsules with different size and layer thickness (and thereby
      different mechanical strength) were used. Deformation in the microchannel was
      observed for all the capsules with a size larger than the constriction height,
      and its extent was mainly governed by the difference between capsule size and
      constriction height. The squeezed microcapsules could recover their original
      spherical shape when the deformation extent was smaller than 16%, whereas
      permanent physical deformation took place when the deformation extent was larger
      than 34%. The capsules filled with polyelectrolytes could greatly enhance their
      shape recovery ability due to the higher osmotic pressure in the capsule interior
      and could well maintain the preloaded low-molecular-weight dyes regardless of the
      squeezing.

PMID- 22381037
TI  - Acute antepartum pyelonephritis in pregnancy: a critical analysis of risk factors
      and outcomes.
AB  - OBJECTIVE: To test the incidence and sonographic parameters of pyelonephritis
      during pregnancy, and to examine risk factors and pregnancy outcomes of women
      with acute antepartum pyelonephritis. STUDY DESIGN: A retrospective population
      based study comparing all singleton pregnancies of patients with and without
      acute antepartum pyelonephritis was performed. Patients lacking prenatal care as
      well as multiple gestations were excluded from the study. Multiple logistic
      regression models were used to control for confounders. RESULTS: Out of 219,612
      singleton deliveries in 1988-2010, 165 women (0.07%) suffered from acute
      antepartum pyelonephritis. Abnormal sonographic findings were found in 85.7% of
      the patients with pyelonephritis. Pyelonephritis was significantly associated
      with nulliparity (46.1% vs. 24.4%, p<0.001), younger maternal age (26.3 +/- 6.0
      vs. 28.6 +/- 5.8 years, p<0.001), intrauterine growth restriction (IUGR) (6.7%
      vs. 2.1%, p<0.001), placental abruption (3.6% vs. 0.7%, p<0.001), low 1 min Apgar
      scores (10.3% vs. 6.0%, p<0.05), urinary tract infection (UTI) (4.2% vs. 0.4%,
      p<0.001) and preterm delivery (less than 37 weeks gestation; 20.0% vs. 7.8%;
      p<0.001). Using a multivariable analysis, independent risk factors for acute
      antepartum pyelonephritis were nulliparity (OR 2.0; 95% C.I 1.4-2.9; p<0.001),
      UTI (OR 10.3; 95% C.I 4.8-22.1; p<0.001) and younger maternal age (OR 0.96; 95%
      C.I 0.93-0.99; p=0.009). Using another multivariable analysis, with preterm
      delivery as the outcome variable, acute antepartum pyelonephritis was found as an
      independent risk factor for preterm delivery (OR 2.6; 95% C.I 1.7-3.9; p<0.001).
      CONCLUSION: Acute antepartum pyelonephritis is associated with adverse perinatal
      outcomes and specifically is an independent risk factor for preterm delivery.

PMID- 22381038
TI  - Association between endometriosis and polymorphisms in insulin-like growth factor
      binding protein genes in Korean women.
AB  - OBJECTIVE: Genetic factors are known to be associated with the development and
      progression of endometriosis, but the genes related to endometriosis have not
      been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed
      to be involved in the proliferation and apoptosis of cells that play an important
      role in the pathophysiologic mechanism of endometriosis. This study aimed to
      determine the association between endometriosis and polymorphisms of the IGFBP
      genes in Korean women. STUDY DESIGN: In a case-control study, the rs1995051,
      rs1065780 and c.759A>G single nucleotide polymorphisms (SNPs) in the IGFBP1 gene
      and the -672A>G, -202A>C and c.95C>G SNPs in the IGFBP3 gene were analyzed in 128
      women with endometriosis and 108 normal control women. RESULTS: The haplotype
      genotype composed of a combination of three IGFBP1 gene polymorphisms was not
      related to endometriosis, while the haplotype genotype of the IGFBP3 gene had a
      significant association with endometriosis. Women not carrying the AAG (-672A/
      202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have a 3.19-times
      higher risk of endometriosis compared with women with AAG homozygotes, and this
      trend was found in women with advanced endometriosis but not in women with early
      endometriosis. CONCLUSIONS: The AAG haplotype allele of the -672A>G, -202A>C and
      c.95C>G polymorphisms in the IGFBP3 gene may be associated with advanced
      endometriosis in Korean women.

PMID- 22381039
TI  - The Arabidopsis SYN3 cohesin protein is important for early meiotic events.
AB  - alpha-Kleisins are core components of meiotic and mitotic cohesin complexes.
      Arabidopsis contains four genes that encode alpha-kleisin proteins: SYN1, SYN2,
      SYN3 and SYN4. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and
      SYN4 appear to be SCC1 orthologs and function in mitosis. SYN3 is essential for
      megagametogenesis and is enriched in the nucleolus of meiotic and mitotic cells.
      In this study the role of SYN3 during meiosis was investigated by
      characterization of plants that express SYN3-RNAi constructs from either meiotic
      DMC1, native SYN3, or inducible PX7 promoters. Reduction of SYN3 caused defects
      in homologous chromosome synapsis and synaptonemal complex (SC) formation during
      male and female meiosis. Consistent with this observation, relatively little
      signal for the SC component ZYP1 was detected on the chromosomes of SYN3-RNAi
      plants. ZYP1 transcript levels were relatively normal, but several transcripts
      for genes that encode proteins involved in meiotic recombination were altered,
      which suggested that a reduction in SYN3 may inhibit meiotic progression by
      alteration of meiotic gene expression.

PMID- 22381040
TI  - The UK EndoVascular Aneurysm Repair (EVAR) trials: randomised trials of EVAR
      versus standard therapy.
AB  - OBJECTIVE: To assess the efficacy of endovascular aneurysm repair (EVAR) against
      standard alternative management in patients with large abdominal aortic aneurysm
      (AAA). DESIGN: Two national, multicentre randomised trials - EVAR trials 1 and 2.
      SETTING: Patients were recruited from 38 out of 41 eligible UK hospitals.
      PARTICIPANTS: Men and women aged at least 60 years, with an AAA measuring at
      least 5.5 cm on a computerised tomography scan that was regarded as anatomically
      suitable for EVAR, were assessed for fitness for open repair. Patients considered
      fit were randomised to EVAR or open repair in EVAR trial 1 and patients
      considered unfit were randomised to EVAR or no intervention in EVAR trial 2.
      INTERVENTIONS: EVAR, open repair or no intervention. MAIN OUTCOME MEASURES: The
      primary outcome was mortality (operative, all-cause and AAA related). Patients
      were flagged at the UK Office for National Statistics with centrally coded death
      certificates assessed by an Endpoints Committee. Power calculations based upon
      mortality indicated that 900 and 280 patients were required for EVAR trials 1 and
      2, respectively. Secondary outcomes were graft-related complications and
      reinterventions, adverse events, renal function, health-related quality of life
      and costs. Cost-effectiveness analyses were performed for both trials. RESULTS:
      Recruitment occurred between 1 September 1999 and 31 August 2004, with targets
      exceeded in both trials: 1252 randomised into EVAR trial 1 (626 to EVAR) and 404
      randomised into EVAR trial 2 (197 to EVAR). Follow-up closed in December 2009
      with very little loss to follow-up (1%). In EVAR trial 1, 30-day operative
      mortalities were 1.8% and 4.3% in the EVAR and open-repair groups, respectively:
      adjusted odds ratio 0.39 [95% confidence interval (CI) 0.18 to 0.87], p = 0.02.
      During a total of 6904 person-years of follow-up, 524 deaths occurred (76 AAA
      related). Overall, there was no significant difference between the groups in
      terms of all-cause mortality: adjusted hazard ratio (HR) 1.03 (95% CI 0.86 to
      1.23), p = 0.72. The EVAR group did demonstrate an early advantage in terms of
      AAA-related mortality, which was sustained for the first few years, but lost by
      the end of the study, primarily due to fatal endograft ruptures: adjusted HR 0.92
      (95% CI 0.57 to 1.49), p = 0.73. The EVAR procedure was more expensive than open
      repair (mean difference L1177) and not found to be cost-effective, but the model
      was sensitive to alternative assumptions. In EVAR trial 2, during a total of 1413
      person-years of follow-up, a total of 305 deaths occurred (78 AAA related). The
      30-day operative mortality was 7.3% in the EVAR group. However, this group later
      demonstrated a significant advantage in terms of AAA-related mortality, but this
      became apparent only after 4 years: overall adjusted HR 0.53 (95% CI 0.32 to
      0.89), p = 0.02. Sadly, this advantage did not result in any benefit in terms of
      all-cause mortality: adjusted HR 0.99 (95% CI 0.78 to 1.27), p = 0.97. Overall,
      EVAR was more expensive than no intervention (mean difference L10,222) and not
      found to be cost-effective. CONCLUSIONS: EVAR offers a clear operative mortality
      benefit over open repair in patients fit for both procedures, but this early
      benefit is not translated into a long-term survival advantage. Among patients
      unfit for open repair, EVAR is associated with a significant long-term reduction
      in AAA-related mortality but this does not appear to influence all-cause
      mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 55703451.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 16,
      No. 9. See the HTA programme website for further project information.

PMID- 22381041
TI  - Shifts in reproductive assurance strategies and inbreeding costs associated with
      habitat fragmentation in Central American mahogany.
AB  - The influence of habitat fragmentation on mating patterns and progeny fitness in
      trees is critical for understanding the long-term impact of contemporary
      landscape change on the sustainability of biodiversity. We examined the
      relationship between mating patterns, using microsatellites, and fitness of
      progeny, in a common garden trial, for the insect-pollinated big-leaf mahogany,
      Swietenia macrophylla King, sourced from forests and isolated trees in 16
      populations across Central America. As expected, isolated trees had disrupted
      mating patterns and reduced fitness. However, for dry provenances, fitness was
      negatively related to correlated paternity, while for mesic provenances, fitness
      was correlated positively with outcrossing rate and negatively with correlated
      paternity. Poorer performance of mesic provenances is likely because of reduced
      effective pollen donor density due to poorer environmental suitability and
      greater disturbance history. Our results demonstrate a differential shift in
      reproductive assurance and inbreeding costs in mahogany, driven by exploitation
      history and contemporary landscape context.

PMID- 22381042
TI  - Expression and purification of hepatitis B surface antigen S from Escherichia
      coli; a new simple method.
AB  - BACKGROUND: Hepatitis B is a liver disease primarily caused by hepatitis B virus
      (HBV) infection. It is distributed worldwide and associated with high mortality
      and morbidity rates. HBV infections can be avoided by the administration of the
      currently available vaccine and can be easily diagnosed through commercially
      available kits. Both the vaccine and the diagnostic kits depend on using the
      hepatitis B surface antigen (HBsAg) as an antigen. Developing countries such as,
      Egypt, suffer from the widespread of HBV infections and the limited resources to
      provide adequate supplies of either the vaccine or the diagnostic kits. Therefore
      the need for an easy, rapid, low cost method to produce HBsAg is urgently needed
      within this setting. FINDINGS: To achieve this goal, the gene encoding the
      HBsAg(S) protein was cloned and expressed as a fusion protein with a GST tag in
      Escherichia coli. The recombinant protein was successfully expressed and purified
      in both good quality and quantity. CONCLUSIONS: The simplified and the relatively
      low cost of the used protocol make this an attractive alternative to protocols
      currently used for the purification of HBsAg(S). The exploiting of this
      achievement for new diagnostics can be directed for application in the developing
      countries where they are extremely needed.

PMID- 22381043
TI  - Contribution of CYP2C19 and CYP3A4 to the formation of the active nortilidine
      from the prodrug tilidine.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The analgesic activity of tilidine is
      mediated by its active metabolite, nortilidine, which easily penetrates the blood
      brain barrier and binds to the u-opioid receptor as a potent agonist. Tilidine
      undergoes an extensive first-pass metabolism, which has been suggested to be
      mediated by CYP3A4 and CYP2C19; furthermore, strong inhibition of CYP3A4 and
      CYP2C19 by voriconazole increased exposure of nortilidine, probably by inhibition
      of further metabolism. The novel CYP2C19 gene variant CYP2C19*17 causes
      ultrarapid drug metabolism, in contrast to the *2 and *3 variants, which result
      in impaired drug metabolism. WHAT THIS STUDY ADDS: Using a panel study with
      CYP2C19 ultrarapid and poor metabolizers, a major contribution of polymorphic
      CYP2C19 on tilidine metabolic elimination can be excluded.  The potent CYP3A4
      inhibitor ritonavir alters the sequential metabolism of tilidine, substantially
      reducing the partial metabolic clearances of tilidine to nortilidine and
      nortilidine to bisnortilidine, which increases the nortilidine exposure twofold.
      The lowest clearance in overall tilidine elimination is the N-demethylation of
      nortilidine to bisnortilidine. Inhibition of this step leads to accumulation of
      the active nortilidine. AIMS: To investigate in vivo the effect of the CYP2C19
      genotype on the pharmacokinetics of tilidine and the contribution of CYP3A4 and
      CYP2C19 to the formation of nortilidine using potent CYP3A4 inhibition by
      ritonavir. METHODS: Fourteen healthy volunteers (seven CYP2C19 poor and seven
      ultrarapid metabolizers) received ritonavir orally (300 mg twice daily) for 3
      days or placebo, together with a single oral dose of tilidine and naloxone (100
      mg and 4 mg, respectively). Blood samples and urine were collected for 72 h.
      Noncompartmental analysis was performed to determine pharmacokinetic parameters
      of tilidine, nortilidine, bisnortilidine and ritonavir. RESULTS: Tilidine
      exposure increased sevenfold and terminal elimination half-life fivefold during
      ritonavir treatment, but no significant differences were observed between the
      CYP2C19 genotypes. During ritonavir treatment, nortilidine area under the
      concentration-time curve was on average doubled, with no differences between
      CYP2C19 poor metabolizers [2242 h ng ml(-1) (95% confidence interval 1811-2674)
      vs. 996 h ng ml(-1) (95% confidence interval 872-1119)] and ultrarapid
      metabolizers [2074 h ng ml(-1) (95% confidence interval 1353-2795) vs. 1059 h ng
      ml(-1) (95% confidence interval 789-1330)]. The plasma concentration-time curve
      of the secondary metabolite, bisnortilidine, showed a threefold increase of time
      to reach maximal observed plasma concentration; however, area under the
      concentration-time curve was not altered by ritonavir. CONCLUSIONS: The
      sequential metabolism of tilidine is inhibited by the potent CYP3A4 inhibitor,
      ritonavir, independent of the CYP2C19 genotype, with a twofold increase in the
      exposure of the active nortilidine.

PMID- 22381044
TI  - A retrospective audit of anesthetic techniques and complications in children with
      mucopolysaccharidoses.
AB  - OBJECTIVES AND AIMS: To document the incidence of difficult airway management and
      difficult intubation in the era of replacement therapy for Australian children
      with mucopolysaccharidosis (MPS). BACKGROUND: Medical treatment for MPS has
      developed significantly since 1980's with a large number of patients now being
      offered either bone marrow transplant or enzyme replacement. The impact of these
      therapies on the incidence of difficult airway management has not been adequately
      documented. Similarly, anesthesia techniques and airway devices have been
      developed, which are thought to have greatly increased the safety of managing
      these patients under anesthesia but their role in children with MPS has not been
      systematically described. METHODS: A retrospective chart review of 17 patients
      with MPS who had received anesthetics at the Royal Children's Hospital during the
      time frame January 1998-January 2011. The primary outcome was the incidence of
      difficult or failed intubation. Secondary outcomes were the relationship between
      the incidence of difficult intubation and treatment with enzyme replacement
      therapy (ERT) or bone marrow transplantation. RESULTS: Seventeen patients
      received 141 anesthetics for 214 procedures. Difficult face mask ventilation
      occurred in 20 anesthetics (14.2%). Difficult intubation occurred in 40
      anesthetics (25%). Failed intubation occurred in two cases (1.6%).The incidence
      of difficult intubation was 12% in MPS I, 35% MPS II, 86.7% in MPS VI, and 0% in
      MPS III and IV. CONCLUSIONS: Hematopoietic stem cell transplantation prior to 2
      years of age reduces the incidence of difficult mask ventilation and difficult
      intubation in children with MPS I. ERT was initiated late in the clinical course
      of MPS II and VI and induced improvements in upper airway patency but did not
      reduce the incidence of difficult airway management.

PMID- 22381045
TI  - Neonatal size in term children is associated with asthma at age 7, but not with
      atopic dermatitis or allergic sensitization.
AB  - BACKGROUND: We hypothesized that anthropometrics in the newborn is associated
      with development of asthma later in life. METHODS: The study included a
      prospective, longitudinal clinical study of a birth cohort of 411 Danish neonates
      born at term of mothers with a history of asthma. The primary endpoint was
      physician-diagnosed asthma at age 7 years. Allergic sensitization and atopic
      dermatitis (AD) were also investigated. Infant size was measured at the research
      clinic on four occasions during the first year of life. Risk for asthma, AD, and
      allergic sensitization at age 6-7 were estimated from logistic regression. Time
      to first asthma and AD were investigated by Cox regression. Multivariate models
      were adjusted for gender, gestational age, and mothers smoking during pregnancy.
      RESULTS: Neonatal weight, length, body mass index and head circumference (z
      score) were all significantly associated with asthma at age 7. Adjusted odds
      ratio for asthma by estimated birth weight z-score: 1.87 [1.23-2.84]; P = 0.004.
      Adjusted HR for onset of asthma by neonatal weight z-score: 1.46 [1.08-1.96]; P =
      0.013. Neonatal size did not associate with AD or allergic sensitization.
      CONCLUSIONS: Increased neonatal size was significantly associated with asthma at
      age 7 but not AD or allergic sensitization in at-risk children born at term. The
      findings suggest some common prenatal mechanisms linking body size and asthma.

PMID- 22381046
TI  - Visual performance in preterm infants with brain injuries compared with low-risk
      preterm infants.
AB  - BACKGROUND: Neonatal brain injuries are the main cause of visual deficit produced
      by damage to posterior visual pathways. While there are several studies of visual
      function in low-risk preterm infants or older children with brain injuries,
      research in children of early age is lacking. AIM: To assess several aspects of
      visual function in preterm infants with brain injuries and to compare them with
      another group of low-risk preterm infants of the same age. STUDY DESIGN AND
      SUBJECTS: Forty-eight preterm infants with brain injuries and 56 low-risk preterm
      infants. OUTCOME MEASURES: The ML Leonhardt Battery of Optotypes was used to
      assess visual functions. This test was previously validated at a post-menstrual
      age of 40 weeks in newborns and at 30-plus weeks in preterm infants. RESULTS: The
      group of preterm infants with brain lesions showed a delayed pattern of visual
      functions in alertness, fixation, visual attention and tracking behavior compared
      to infants in the healthy preterm group. The differences between both groups, in
      the visual behaviors analyzed were around 30%. These visual functions could be
      identified from the first weeks of life. CONCLUSION: Our results confirm the
      importance of using a straightforward screening test with preterm infants in
      order to assess altered visual function, especially in infants with brain
      injuries. The findings also highlight the need to provide visual stimulation very
      early on in life.

PMID- 22381047
TI  - Anti-inflammatory and PPAR transactivational effects of secondary metabolites
      from the roots of Asarum sieboldii.
AB  - Phytochemical study on the roots of Asarum sieboldii resulted in the isolation of
      one new compound, (1R,2S,5R,6R)-5'-O-methylpluviatilol (1) and 12 known compounds
      (2-13). Their structures were determined by extensive spectroscopic methods,
      including 1D and 2D NMR, and MS spectra. The absolute configuration of compound 1
      was established using CD spectrum. Compounds 4, 5, and 12/13 significantly
      inhibited TNFalpha-induced NF-kappaB transcriptional activity in HepG2 cells in a
      dose-dependent manner, with IC(50) values ranging from 6.4 to 9.4 MUM.
      Furthermore, the transcriptional inhibitory function of these compounds was
      confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells.
      Compounds 1-3, 6,7, 10, and 11 significantly activated the transcriptional
      activity of PPARs in a dose-dependent manner, with EC(50) values ranging from 1.7
      to 20.9 MUM. Compounds 7, 10, and 11 exhibited significant dose-dependent
      PPARalpha transactivational activity, with EC(50) values of 19.5, 15.7, and 4.0
      MUM, respectively. Compounds 1, 6, 7, 10, and 11 activated PPARgamma
      transcriptional activity, with EC(50) values ranging from 3.6 to 22.6 MUM,
      whereas compounds 10 and 11 significantly increased PPARbeta(delta)
      transactivational activity, with EC(50) values of 22.6 and 4.9 MUM, respectively.
      These results provide a scientific support for the use of the roots of A.
      sieboldii and warrant further studies to develop new agents for the prevention
      and treatment of the inflammatory and metabolic diseases.

PMID- 22381048
TI  - Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6
      tetrahydropyridines as 5-HT2C agonists.
AB  - A series of substituted 4-arylpiperidines and a smaller family of 4-aryl-1,2,3,6
      tetrahydropyridines were synthesized and their biological activity at the 5
      HT(2C) receptor studied to determine whether either series showed noteworthy
      agonist activity. Structure-activity relationships were developed from the
      performed receptor binding assays and functional studies, and the results of the
      analysis are presented herein.

PMID- 22381049
TI  - Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: a practical
      access via Pd/C-Cu catalysis.
AB  - The design and synthesis of 4-alkynyl pyrazole derivatives has led to the
      identification of new class of PDE4 inhibitors. All these compounds were accessed
      for the first time via a facile Pd/C-CuI-PPh(3) mediated C-C bond forming
      reaction between an appropriate pyrazole iodide and various terminal alkynes. In
      vitro PDE4B inhibitory properties and molecular modeling studies of some of the
      compounds synthesized indicated that 4-alkynyl pyrazole could be a promising
      template for the discovery of novel PDE4 inhibitors.

PMID- 22381050
TI  - Scaffold hybridization in generation of indenoindolones as anticancer agents that
      induce apoptosis with cell cycle arrest at G2/M phase.
AB  - Scaffold hybridization of several natural and synthetic anticancer leads led to
      the consideration of indenoindolones as potential novel anticancer agents. A
      series of these compounds were prepared by a diversity-feasible synthetic method.
      They were found to possess anticancer activities with higher potency compared to
      etoposide and 5-fluorouracil in kidney cancer cells (HEK 293) and low toxicity to
      corresponding normal cells (Vero). They exerted apoptotic effect with blocking of
      cell cycle at G2/M phase.

PMID- 22381051
TI  - Comparison of pulmonary morbidity using sevoflurane or propofol-remifentanil
      anesthesia in an Ivor Lewis operation.
AB  - OBJECTIVE: An inhalation anesthetic-induced attenuation effect on the
      inflammatory reaction during one-lung ventilation (OLV) has been reported.
      Pulmonary inflammation is a substantive prognostic factor for Ivor Lewis
      operations. Blood inflammatory parameters and postoperative pulmonary
      complications between sevoflurane and propofol-remifentanil anesthesia in
      patients undergoing Ivor Lewis operations were compared. DESIGN: A prospective,
      randomized study. SETTING: A medical university. PARTICIPANTS: Forty-eight
      patients undergoing Ivor Lewis operation allocated randomly into 2 groups.
      INTERVENTIONS: Patients received sevoflurane or total intravenous anesthesia
      using propofol and remifentanil (n = 24 per group). MEASUREMENTS AND MAIN
      RESULTS: Blood interleukin-6 (IL-6), malondialdehyde (MDA), oxygenation,
      abnormalities on a chest radiograph (CXR), extubation, intensive care unit (ICU)
      stay, length of hospitalization, and postoperative complications were compared
      between the 2 anesthetic techniques. The level of IL-6 at the end of surgery was
      lower for sevoflurane (69.5 [35.9-121.0] pg/mL) than propofol-remifentanil (128.2
      [92.8-163.8] pg/mL, p = 0.03), but this difference was not maintained 24 hours
      after surgery. Frequencies of abnormalities measured by a CXR,
      PaO(2)/F(I)O(2)<300, and PaCO(2) <50 mmHg until discharge, the postoperative
      highest C-reactive protein level, white blood cells, and MDA did not differ
      between the 2 anesthetics. No differences in the extubation time, ICU stay,
      discharge day, or the incidence of hospital complications between sevoflurane and
      propofol-remifentanil anesthesia techniques were observed. CONCLUSIONS:
      Sevoflurane anesthesia attenuated an increase in blood IL-6 at the end of surgery
      but did not provide any advantages over propofol remifentanil in terms of
      postoperative pulmonary complications in Ivor Lewis operations.

PMID- 22381052
TI  - Incidental vascular flaps on neck ultrasound.

PMID- 22381053
TI  - Large-area organization of pNIPAM-coated nanostars as SERS platforms for
      polycyclic aromatic hydrocarbons sensing in gas phase.
AB  - Here, a new surface enhanced Raman spectroscopy (SERS) platform suitable for gas
      phase sensing based on the extended organization of poly-N-isopropylacrylamide
      (pNIPAM)-coated nanostars over large areas is presented. This system yields high
      and homogeneous SERS intensities, and simultaneously traps organic chemical
      agents as pollutants from the gas phase. pNIPAM-coated gold nanostars were
      organized into parallel linear arrays. The optical properties of the fabricated
      substrates are investigated, and applicability for advanced sensing is
      demonstrated through the detection in the gas phase of pyrene traces, a well
      known polyaromatic hydrocarbon.

PMID- 22381054
TI  - What can optometrists do to prevent eye injuries?

PMID- 22381056
TI  - Genetically engineered plasmonic nanoarrays.
AB  - In the present Letter, we demonstrate how the design of metallic nanoparticle
      arrays with large electric field enhancement can be performed using the basic
      paradigm of engineering, namely the optimization of a well-defined objective
      function. Such optimization is carried out by coupling a genetic algorithm with
      the analytical multiparticle Mie theory. General design criteria for best
      enhancement of electric fields are obtained, unveiling the fundamental interplay
      between the near-field plasmonic and radiative photonic coupling. Our
      optimization approach is experimentally validated by surface-enhanced Raman
      scattering measurements, which demonstrate how genetically optimized arrays,
      fabricated using electron beam lithography, lead to order of ten improvement of
      Raman enhancement over nanoparticle dimer antennas, and order of one hundred
      improvement over optimal nanoparticle gratings. A rigorous design of nanoparticle
      arrays with optimal field enhancement is essential to the engineering of numerous
      nanoscale optical devices such as plasmon-enhanced biosensors, photodetectors,
      light sources and more efficient nonlinear optical elements for on chip
      integration.

PMID- 22381057
TI  - [How to manage a claim for medical and technical error].
AB  - PURPOSE: The fast modifications in French medical legislation, the increasing
      number of litigations and the professional consequences for the practitioner
      warrant the necessity to recall the "how to manage" a claim for medical error.
      PATIENTS AND METHODS: Four cases of legal action against oncologists are
      presented. RESULTS AND DISCUSSION: The importance of quality and traceability of
      the given information, the essential pieces of the medical file, the description
      of the different process steps and of the contradictory meeting are presented and
      discussed. CONCLUSION: Beyond the control of medical and technical risks, the
      practitioners in general and the radiation oncologist in particular should learn
      on the daily management of the risk related to medical claim.

PMID- 22381058
TI  - WITHDRAWN: Effective Communication with Patients.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.nepr.2011.10.004. The
      duplicate article has therefore been withdrawn.

PMID- 22381059
TI  - Barriers or barricades.

PMID- 22381060
TI  - What design features are used in effective e-health interventions? A review using
      techniques from Critical Interpretive Synthesis.
AB  - The effectiveness of e-health interventions varies greatly. Despite this, there
      has been relatively little formal consideration of how differences in the design
      of an intervention (i.e., how the content is delivered) may explain why some
      interventions are more effective than others. This review primarily examines the
      use of the Internet to provide educational and self-management interventions to
      promote health. The article develops hypotheses about how the design of these
      interventions may be associated with outcomes. In total, 52 published reports
      from both a diversity sample and a representative sample were reviewed using
      techniques from Critical Interpretive Synthesis. Four core interactive design
      features were identified that may mediate the effects of intervention design on
      outcomes: Social context and support, contacts with intervention, tailoring, and
      self-management. A conceptual framework to summarize the design of e-health
      interventions delivered using the Internet is proposed. The framework provides a
      guide for systematic research to identify the effects of specific design features
      on intervention outcomes and to identify the mechanisms underlying any effects.
      To optimize the design of e-health interventions more work is needed to
      understand how and why these design features may affect intervention outcomes and
      to investigate the optimal implementation and dosage of each design feature.

PMID- 22381061
TI  - Who uses telehealth? Setting a usage baseline for the early identification of
      pandemic influenza activity.
AB  - OBJECTIVE: To describe Ontario Telehealth usage for respiratory complaints during
      normal (i.e., interpandemic) circumstances. METHODS: Descriptive analyses were
      conducted on symptom calls of a respiratory nature made to Ontario (Canada)
      Telehealth during a 25-month period. RESULTS: Approximately 300,000 calls were
      made during the period under study, peaking annually in January/February. Calls
      were above average during the weekend and Mondays (p<0.0001). All-ages
      consultation rate was 0.21/1,000 (range, 0.11-0.43). Standardized call rates
      suggested an inverse relationship between age and call rate (except for >65 years
      of age). During peak activity, weekly telehealth call rates were up to more than
      twice the weekly mean and up to four times as high as the lowest weekly rate.
      Highest call rate was for under 5 years old (158.4/1,000). Male rates exceed
      female call rates in younger age groups; the pattern reversed in older age
      groups. The relationship between income and call pattern showed that income and
      call patterns were (1) directly related for under 5 years old, (2) inversely
      related for callers aged 45 years and above, and (3) bimodal (higher call rates
      in both the highest and lowest income groups) for callers 5-44 years old.
      DISCUSSION: The advent of annual respiratory illness seasons under study here
      resulted in surge capacity. Data such as these can and should be used for
      exercises such as seasonal and pandemic forecasting. Also, recent pandemic
      experience has showed us monitoring both overall exceedances in usage and
      deviances from established demographic patterns could enhance existing routine
      surveillance.

PMID- 22381062
TI  - Synthesis, structure-activity relationship, and pharmacophore modeling studies of
      pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors.
AB  - Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to
      healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine
      protease, has been rapidly emerging as an effective therapeutic target for the
      treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring
      the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated
      approach of structure-based virtual screening, chemical synthesis, and bioassay.
      Virtual screening of SPECS Database, followed by enzymatic activity assay,
      resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds
      (1-5) with different scaffold. Compound 1 was selected for the further structure
      modifications in considering inhibitory activity, structural variability, and
      synthetic accessibility. Seventeen new compounds were synthesized and tested with
      biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show
      inhibitory effects against DPP-4. Molecular docking models give rational
      explanation about structure-activity relationships. Based on eight DPP-4
      inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was
      obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor
      (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore
      mapping results are in agreement with pharmacological results. The present
      studies give some guiding information for further structural optimization and are
      helpful for future DPP-4 inhibitors design.

PMID- 22381064
TI  - Realistic losses of rare species disproportionately impact higher trophic levels.
AB  - Predicting the consequences of changes in biodiversity requires understanding
      both species' susceptibility to extirpation and their functional roles in
      ecosystems. However, few studies have evaluated the effects of realistic, non
      random biodiversity losses, severely limiting the applicability of biodiversity
      research to conservation. Here, we removed sessile species from a rocky shore
      community in a way that deliberately mimicked natural patterns of species loss.
      We found that the rarest species in the system act from the bottom up to
      disproportionately impact the diversity and abundance of consumers. Realistic
      losses of rare species in a diverse assemblage of seaweeds and sessile
      invertebrates, collectively comprising <10% of sessile biomass, resulted in a 42
      47% decline in consumer biomass. In contrast, removal of an equivalent biomass of
      dominant sessile species had no effect on consumers. Our results highlight the
      'cornerstone' role that rare species can play in shaping the structure of the
      community they support.

PMID- 22381063
TI  - Individualization of cancer treatment from radiotherapy perspective.
AB  - Radiotherapy is today used in about 50% of all cancer patients, often in
      multidisciplinary approaches. With major advance in radiotherapy techniques,
      increasing knowledge on tumor genetics and biology and the continuous
      introduction of specifically targeted drugs into combined radio-oncological
      treatment schedules, individualization of radiotherapy is of high priority to
      further improve treatment outcomes, i.e. to increase long-term tumor cure and/or
      to reduce chronic treatment toxicity. This review gives an overview on the
      importance of predictive biomarkers for the field of radiation oncology. The
      current status of knowledge on potential biomarkers of tumor hypoxia, tumor cell
      metabolism, DNA repair, cancer stem cells and biomarkers for combining
      radiotherapy with inhibition of the epidermal growth factor receptor using
      monoclonal antibodies is described.

PMID- 22381065
TI  - Evaluation of a bibliotherapy manual for reducing psychological distress in
      people with depression: a randomized controlled trial.
AB  - AIM: This article reports a study to evaluate the efficacy of a self-help manual
      in reducing psychological distress in individuals with moderate depression.
      BACKGROUND: The prevalence of depression in Thailand is increasing markedly (e.g.
      from 56-197 per 100,000 population between 1997-2007). DESIGN: We conducted a
      randomized controlled trial with 54 outpatients with depression in Chiang Mai
      Province in Thailand. METHOD: Participants were assigned randomly to an
      intervention or control group. The intervention group participants were given a
      self-help manual in addition to standard care and treatment while the control
      group received standard care and treatment. Psychological distress was measured
      with the Kessler Psychological Distress Scale. Data were collected between
      October 2007-April 2008. RESULTS: The findings showed statistically significant
      differences between both groups in their levels of psychological distress (e.g.
      tiredness, hopelessness, restlessness). At post-test, the distress scores of the
      intervention group were lower than those in the control group. Between post-test
      and 1-month follow-up, distress scores continued to decrease steadily in the
      intervention group but only decreased slightly in the control group. CONCLUSION:
      The findings affirm the benefits of bibliotherapy or self-help therapy in book
      form in helping to reduce psychological distress in people with moderate
      depression. The approach is easy to use and can be incorporated as an adjunct to
      standard care and treatment. Bibliotherapy can be used by community mental health
      nurses and other clinicians to reduce psychological distress and promote recovery
      in people with moderate depression.

PMID- 22381066
TI  - The tetramethoxyflavone zapotin selectively activates protein kinase C epsilon,
      leading to its down-modulation accompanied by Bcl-2, c-Jun and c-Fos decrease.
AB  - Zapotin, a tetramethoxyflavone, is a natural compound with a wide spectrum of
      activities in neoplastic cells. Protein kinase C epsilon (PKCepsilon) has been
      shown to be oncogenic, with the ability to increase cell migration, invasion and
      survival of tumor cells. Here we report that zapotin inhibits cell proliferation.
      In wild-type HeLa cells with basal endogenous expression of PKCepsilon, the
      IC(50) was found to be 17.9 +/- 1.6 MUM. In HeLa cells overexpressing doxycycline
      inducible constitutively active PKCepsilon (HeLaPKCepsilonA/E), the IC(50) was
      7.6 +/- 1.3 MUM, suggesting that PKCepsilon enhances the anti-proliferative
      effect of zapotin. Moreover, we found that zapotin selectively activated
      PKCepsilon in comparison with other PKC family members, but attenuated
      doxycycline-induced PKCepsilon expression. As a result of zapotin treatment for
      6, 12 and 24h, the doxycycline-induced levels of the two differently
      phosphorylated PKCepsilon forms (87 kDa and 95 kDa) were decreased. Migration
      assays revealed that increasing concentrations of zapotin (from 3.5 to 15 MUM)
      decreased migration of HeLaPKCepsilonA/E cells. Furthermore, zapotin
      significantly increased the fraction of apoptotic cells in doxycycline-induced
      (HeLaPKCepsilonA/E) cells after 24h and decreased the levels of Bcl-2, c-Jun, c
      Fos. This was accompanied by a degradation of PARP-1. In summary, activation of
      PKCepsilon and down-modulation of the induced PKCepsilon level by zapotin were
      associated with decreased migration and increased apoptosis. These observations
      are consistent with the previously reported chemopreventive and chemotherapeutic
      action of zapotin.

PMID- 22381067
TI  - MRP4 and CFTR in the regulation of cAMP and beta-adrenergic contraction in
      cardiac myocytes.
AB  - Spatiotemporal regulation of cAMP in cardiac myocytes is integral to regulating
      the diverse functions downstream of beta-adrenergic stimulation. The activities
      of cAMP phosphodiesterases modulate critical and well-studied cellular processes.
      Recently, in epithelial and smooth muscle cells, it was found that the multi-drug
      resistant protein 4 (MRP4) acts as a cAMP efflux pump to regulate intracellular
      cAMP levels and alter effector function, including activation of the cAMP
      stimulated Cl(-) channel, CFTR (cystic fibrosis transmembrane conductance
      regulator). In the current study we investigated the potential role of MRP4 in
      regulating intracellular cAMP and beta-adrenergic stimulated contraction rate in
      cardiac myocytes. Cultured neonatal ventricular myocytes were used for all
      experiments. In addition to wildtype mice, beta(1)-, beta(2)-, and
      beta(1)/beta(2)-adrenoceptor, and CFTR knockout mice were used. MRP4 expression
      was probed via Western blot, intracellular cAMP was measured by fluorescence
      resonance energy transfer, while the functional role of MRP4 was assayed via
      monitoring of isoproterenol-stimulated contraction rate. We found that MRP4 is
      expressed in mouse neonatal ventricular myocytes. A pharmacological inhibitor of
      MRP4, MK571, potentiated submaximal isoproterenol-stimulated cAMP accumulation
      and cardiomyocyte contraction rate via beta(1)-adrenoceptors. CFTR expression was
      critical for submaximal isoproterenol-stimulated contraction rate. Interestingly,
      MRP4-dependent changes in contraction rate were CFTR-dependent, however, PDE4
      dependent potentiation of contraction rate was CFTR-independent. We have shown,
      for the first time, a role for MRP4 in the regulation of cAMP in cardiac myocytes
      and involvement of CFTR in beta-adrenergic stimulated contraction. Together with
      phosphodiesterases, MRP4 must be considered when examining cAMP regulation in
      cardiac myocytes.

PMID- 22381068
TI  - The sigma-1 receptor protects against cellular oxidative stress and activates
      antioxidant response elements.
AB  - Sigma-1 receptors are associated with Alzheimer's disease, major depressive
      disorders, and schizophrenia. These receptors show progrowth/antiapoptotic
      properties via their chaperoning functions to counteract ER (endoplasmic
      reticulum) stress, to block neurodegeneration, and to regulate neuritogenesis.
      The sigma-1 receptor knock out mouse offered an opportunity to assess possible
      mechanisms by which the sigma-1 receptor modulates cellular oxidative stress.
      Nuclear magnetic resonance (NMR) metabolomic screening of the WT (wild type) and
      sigma-1 KO (knockout) livers was performed to investigate major changes in
      metabolites that are linked to oxidative stress. Significant changes in protein
      levels were also identified by two-dimensional (2D) gel electrophoresis and mass
      spectrometry. Increased levels of the antioxidant protein peroxiredoxin 6
      (Prdx6), and the ER chaperone BiP (GRP78) compared to WT littermates were
      detected. Oxidative stress was measured in WT and sigma-1 KO mouse liver
      homogenates, in primary hepatocytes and in lung homogenates. Furthermore, sigma-1
      receptor mediated activation of the antioxidant response element (ARE) to
      upregulate NAD(P)H quinone oxidoreductase 1 (NQO1) and superoxide dismutase 1
      (SOD1) mRNA expression in COS cells was shown by RT PCR. These novel functions of
      the sigma-1 receptor were sensitive to well-known sigma ligands via their
      antagonist/agonist properties.

PMID- 22381069
TI  - Protein dependent fate of hepatic cells under nicotine induced stress and
      curcumin ameliorated condition.
AB  - Nicotine is mainly metabolized in liver. Its abuse elicits acute phase response
      by activating macrophages to produce pro-inflammatory cytokines, which play
      critical role in apoptosis or cell proliferation. The protective pharmacological
      mechanism of curcumin against nicotine-induced toxicity on protein malnourished
      liver is still remaining unclear. This study investigated the ameliorative
      mechanism of curcumin against nicotine-induced toxicity and also fate of liver
      particularly under protein restricted condition. Female Albino-rats maintained
      under normal/protein-restricted diets, were subcutaneously injected with nicotine
      tartrate (2.5 mg/kg body weight/day) and orally supplemented with curcumin (80
      mg/kg body weight/day) for 21 days. The animals were then sacrificed to dissect
      out liver and proceed with further experiments. Interactions of nicotine with DNA
      both in vivo and in vitro were observed by thermal denaturation and DNA laddering
      assays. Effects of nicotine on hepatic cells were monitored by differential
      staining, comet assay, cytokine profiling, mRNA and protein expression. Nicotine
      caused more intense DNA damage, promoted hepatic cell death through up-regulating
      pro-apoptotic proteins and signaling molecules in protein malnourished
      individuals. Through up-regulation of anti-apoptotic proteins and proliferation
      promoting molecules, nicotine dysregulated homeostasis in normal protein
      condition. Curcumin significantly ameliorated the nicotine-induced toxicity in
      both conditions and regulated the imbalance between cell survival and death
      induced by nicotine. The protein content present in the nicotine induced hepatic
      cell decides either cell-survival pathway or cytotoxic pathway.

PMID- 22381070
TI  - Small interfering RNA-mediated knockdown of NF-kappaBp65 attenuates neuropathic
      pain following peripheral nerve injury in rats.
AB  - Recent reports show that the nuclear factor-kappaB (NF-kappaB) can control
      numerous genes encoding inflammatory and nociceptive mediators and play an
      important role in the development of central pain sensitization. The aim of the
      present study is to assess the role of NF-kappaB signal pathway and its
      downstream pro-inflammatory cytokines in the modulation of neuropathic pain, by
      using small interfering RNAs (siRNAs) technique, which has been shown to result
      in potent, long-lasting post-transcriptional silencing of specific genes. We
      developed a highly efficient method of lentivirus-mediated delivery of short
      hairpin RNA (shRNA) targeting NF-kappaBp65 for gene silencing. This method
      successfully transduced LV-shNF-kappaBp65 into cultured spinal cord neurons in
      vitro and spinal cord cells in vivo, inhibited the expression of NF-kappaBp65 and
      pro-inflammatory factors (TNF-alpha, IL-1beta and IL-6) and alleviated mechanical
      allodynia and thermal hyperalgesia for more than 4weeks in chronic constriction
      injury (CCI) model of rats. Taken together, our results suggest that siRNA
      against NF-kappaBp65 is a potential strategy for analgesia. Furthermore, the
      lentiviral vector derived shRNA approach shows a great promise for the management
      of neuropathic pain and the study of functional NF-kappaBp65 gene expression.

PMID- 22381071
TI  - Unspoken phenomena: using the photovoice method to enrich phenomenological
      inquiry.
AB  - Photovoice is a powerful method that is gaining momentum in nursing research. As
      a relatively new method in nursing science, the situatedness of photovoice within
      or alongside various research methodologies in a single study remains in a stage
      of early development. The purpose of this paper is to discuss the photovoice
      method as a means to elicit phenomenological data when researching the lived
      experience. While the foundational bases of phenomenology and photovoice differ
      substantially, the argument presented in this paper suggests that the photovoice
      method can be successfully used in phenomenological inquiry provided that
      significant rigour checks are pursued. This includes reflecting upon the origins
      and understandings of both methodology and method to promote methodological
      congruency. Data collection and analysis approaches that contribute to
      phenomenological inquiry using the photovoice method in addition to rigour and
      ethical considerations are discussed. The use of data generated from photovoice
      in phenomenological inquiry may fill a void of understanding furnished by
      limitations of traditional phenomenological inquiry and of spoken language and
      can enhance understanding of the lived experience, which may not always be best
      understood by words alone.

PMID- 22381073
TI  - Mumps vaccine effectiveness in primary schools and households, the Netherlands,
      2008.
AB  - To estimate the mumps vaccine effectiveness (VE) during a large genotype D mumps
      outbreak, we conducted a cross-sectional study in eight primary schools and
      associated households in the Netherlands. Questionnaires were used to collect
      information on the occurrence of mumps. Multivariate analyses were used to
      estimate VE. Among schoolchildren we estimated the VE against mumps. Among
      household contacts where the schoolchild was the index case we estimated the VE
      against mumps and against mumps infectiousness. In total 1175 children and 2281
      household contacts participated in the study. The mumps attack rate among
      schoolchildren was 17%. The mumps VE in schoolchildren was 92% [95% confidence
      interval (CI) 83-96%] and 93% [85-97%] for one and two doses of the measles,
      mumps, rubella (MMR) vaccine, respectively. The adjusted mumps VE among household
      contacts was 67% [65-95%] and 11% [-4 to 88%] against mumps and mumps
      infectiousness, respectively. Our study indicates that the mumps component of the
      MMR vaccine offered adequate protection against mumps among schoolchildren. The
      relatively low VE among household contacts is of concern.

PMID- 22381074
TI  - Formulation, stability and immunogenicity of a trivalent pneumococcal protein
      vaccine formulated with aluminum salt adjuvants.
AB  - We investigated the immunogenicity, stability and adsorption properties of an
      experimental pneumococcal vaccine composed of three protein vaccine antigens;
      Pneumococcal histidine triad protein D, (PhtD), Pneumococcal choline-binding
      protein A (PcpA) and genetically detoxified pneumolysin D1 (PlyD1) formulated
      with aluminum salt adjuvants. Immunogenicity studies conducted in BALB/c mice
      showed that antibody responses to each antigen adjuvanted with aluminum hydroxide
      (AH) were significantly higher than when adjuvanted with aluminum phosphate (AP)
      or formulated without adjuvant. Lower microenvironment pH and decreased strength
      of antigen adsorption significantly improved the stability of antigens. The
      stability of PcpA and PlyD1 assessed by RP-HPLC correlated well with the
      immunogenicity of these antigens in mice and showed that pretreatment of the
      aluminum hydroxide adjuvant with phosphate ions improved their stability.
      Adjuvant dose-ranging studies showed that 28 MUg Al/dose to be the concentration
      of adjuvant resulting in optimal immunogenicity of the trivalent vaccine
      formulation. Taken together, the results of theses studies suggest that the type
      of aluminum salt, strength of adsorption and microenvironment pH have a
      significant impact on the immunogenicity and chemical stability of an
      experimental vaccine composed of the three pneumococcal protein antigens, PhtD,
      PcpA, and PlyD1.

PMID- 22381075
TI  - Re-circulation of lymphocytes mediated by sphingosine-1-phosphate receptor-1
      contributes to resistance against experimental infection with the protozoan
      parasite Trypanosoma cruzi.
AB  - T-cell mediated immune responses are critical for acquired immunity against
      infection by the intracellular protozoan parasite Trypanosoma cruzi. Despite its
      importance, it is currently unknown where protective T cells are primed and
      whether they need to re-circulate in order to exert their anti-parasitic effector
      functions. Here, we show that after subcutaneous challenge, CD11c(+)-dependent
      specific CD8(+) T-cell immune response to immunodominant parasite epitopes arises
      almost simultaneously in the draining lymph node (LN) and the spleen. However,
      until day 10 after infection, we observed a clear upregulation of activation
      markers only on the surface of CD11C(+)PDCA1(+) cells present in the LN and not
      in the spleen. Therefore, we hypothesized that CD8(+) T cells re-circulated
      rapidly from the LN to the spleen. We investigated this phenomenon by
      administering FTY720 to T. cruzi-infected mice to prevent egress of T cells from
      the LN by interfering specifically with signalling through sphingosine-1
      phosphate receptor-1. In T. cruzi-infected mice receiving FTY720, CD8 T-cell
      immune responses were higher in the draining LN and significantly reduced in
      their spleen. Most importantly, FTY720 increased susceptibility to infection, as
      indicated by elevated parasitemia and accelerated mortality. Similarly,
      administration of FTY720 to mice genetically vaccinated with an immunodominant
      parasite antigen significantly reduced their protective immunity, as observed by
      the parasitemia and survival of vaccinated mice. We concluded that re-circulation
      of lymphocytes mediated by sphingosine-1-phosphate receptor-1 greatly contributes
      to acquired and vaccine-induced protective immunity against experimental
      infection with a human protozoan parasite.

PMID- 22381072
TI  - Randomised clinical trial of an intensive intervention in the primary care
      setting of patients with high plasma fibrinogen in the primary prevention of
      cardiovascular disease.
AB  - BACKGROUND: We have studied the possible effects of an intensive lifestyle change
      program on plasma fibrinogen levels, in patients with no cardiovascular disease,
      with elevated levels of fibrinogen, normal cholesterol levels, and a moderate
      estimated risk of coronary heart disease (CHD) and we have also analysed whether
      the effect on fibrinogen is independent of the effect on lipids. RESULTS: This
      clinical trial was controlled, unblinded and randomized, with parallel groups,
      done in 13 Basic Health Areas (BHA) in l'Hospitalet de Llobregat (Barcelona) and
      Barcelona city. The study included 436 patients, aged between 35 and 75 years,
      with no cardiovascular disease, elevated levels of fibrinogen (> 300 mg/dl),
      cholesterol < 250 mg/dl, 218 of whom received a more intensive intervention
      consisting of advice on lifestyle and treatment. The follow-up frequency of the
      intervention group was every 2 months. The other 218 patients followed their
      standard care in the BHAs. Fibrinogen, plasma cholesterol and other clinical
      biochemistry parameters were assessed.The evaluation of the baseline
      characteristics of the patients showed that both groups were homogenous. Obesity
      and hypertension were the most prevalent risk factors. After 24 months of the
      study, statistically significant changes were seen between the adjusted means of
      the two groups, for the following parameters: fibrinogen, plasma cholesterol,
      systolic and diastolic blood pressure and body mass index. CONCLUSION: Intensive
      intervention to achieve lifestyle changes has shown to be effective in reducing
      some of the estimated CHD factors. However, the effect of intensive intervention
      on plasma fibrinogen levels did not correlate with the variations in cholesterol.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01089530.

PMID- 22381076
TI  - Analysis of cause of failure of new targeting peptide in PEGylated liposome:
      molecular modeling as rational design tool for nanomedicine.
AB  - Drug nanocarriers are often derivatized with targeting moieties to achieve site
      specific delivery, however, the results from this approach have, as yet, not
      reached expectations. We have tested a new phage display based targeting moiety,
      the activated endothelium targeting peptide (AETP), for its vascular endothelium
      directed targeting efficiency, when anchored to a PEGylated liposome via
      maleimide chemistry. Our results have, however, not shown any evidence of
      improved targeting. We have hypothesized that the failure of the AETP moiety is
      due to its availability to target receptors being restricted, as a result of
      steric hindrance due to the PEG polymer, and possibly affinity for bloodstream
      proteins, particularly human serum albumin (HSA). In this context, molecular
      modeling was used to contrast the properties of the AETP moiety to those of the
      RGD targeting peptide, already found to be effective in previous trials. Our
      molecular dynamics simulation results indicate the AETP moiety is located within
      the PEG layer, and its hydrophobic nature causes it to be obscured by PEG to a
      greater extent than the more hydrophilic RGD targeting peptide. Protein-ligand
      docking results indicated similar affinities for HSA of both the AETP moiety and
      a PEG fragment, and a significantly lower affinity for the RGD peptide. We know
      of no means to investigate this experimentally with atomic level resolution, thus
      our use of computational methods to investigate this can be seen as a new tool
      for rational design in nanomedicine.

PMID- 22381077
TI  - Harvesting energy from water flow over graphene?
AB  - It is reported excitingly in a previous letter (Nano Lett. 2011, 11, 3123) that a
      small piece of graphene sheet about 30 * 16 MUm(2) immersed in flowing water with
      0.6 M hydrochloric acid can produce voltage ~20 mV. Here we find that no
      measurable voltage can be induced by the flow over mono-, bi- and trilayered
      graphene samples of ~1 * 1.5 cm(2) in size in the same solution once the
      electrodes on graphene are isolated from interacting with the solution, mainly
      because the H(3)O(+) cations in the water adsorb onto graphene by strong covalent
      bonds as revealed by our first-principles calculations. When both the graphene
      and its metal electrodes are exposed to the solution as in the previous work,
      water flow over the graphene-electrode system can induce voltages from a few to
      over a hundred millivolts. In this situation, the graphene mainly behaves as a
      load connecting between the electrodes. Therefore, the harvested energy is not
      from the immersed carbon nanomaterials themselves in ionic water flow but
      dominated by the exposed electrodes.

PMID- 22381078
TI  - Cationic nanohydrogel particles as potential siRNA carriers for cellular
      delivery.
AB  - Oligonucleotides such as short, double-stranded RNA (siRNA) or plasmid DNA (pDNA)
      promise high potential in gene therapy. For pharmaceutical application, however,
      adequate drug carriers are required. Among various concepts progressing in the
      market or final development, nanosized hydrogel particles may serve as novel
      transport media especially for siRNA. In this work, a new concept of synthesizing
      polymeric cationic nanohydrogels was developed, which offers a promising strategy
      to complex and transport siRNA into cells. For this purpose, amphiphilic reactive
      ester block copolymers were synthesized by RAFT polymerization of
      pentafluorophenyl methacrylate as reactive ester monomer together with
      tri(ethylene glycol)methyl ether methacrylate. In polar aprotic solvents, a self
      assembly of these polymers could be observed leading to the formation of
      nanometer-sized polymer aggregates. The resulting superstructures were used to
      convert the reactive precursor block copolymers with amine-containing cross
      linker molecules into covalently stabilized hydrogel particles. Detailed dynamic
      light scattering studies showed that the structure of the self-assembled
      aggregates can permanently be locked-in by this process. This method offers a new
      possibility to synthesize precise nanohydrogels of different size starting from
      various block copolymers. Moreover, via reactive ester approach, further
      functionalities could be attached to the nanoparticle, such as fluorescent dyes,
      which allowed distinct tracing of the hydrogels during complexation with siRNA or
      cell uptake experiments. In this respect, cellular uptake of the particles
      themselves as well as with its payload could be detected successfully. Looking
      ahead, these novel cationic nanohydrogel particles may serve as a new platform
      for proper siRNA delivery systems.

PMID- 22381079
TI  - Treatment adherence redefined: a critical analysis of technotherapeutics.
AB  - Treatment adherence issues in the context of chronic illnesses have become an
      important concern worldwide and a top priority in the field of health-care. The
      development of devices that will allow healthcare providers to track treatment
      adherence and monitor physiological parameters with exact precision raises
      important questions and concerns. The aim of this study is to interrogate the use
      of these new technological devices which allow for previously unavailable data to
      be recorded on an ongoing basis and transmitted via a tiny microchip inserted
      into the body. Drawing on the work of Michel Foucault, we analyze how this
      anatomo-political and bio-political instrument serves to discipline chronically
      ill individuals and govern the health of entire populations who suffer from
      chronic conditions. To support our analysis, this article comprises three
      sections. First, we provide an overview of treatment adherence and
      technotherapeutics. Then, we explain how technotherapeutics concern the
      government of bodies and conducts at the individual level and population level
      more generally. Lastly, we provide an example of how this analysis can be
      connected to routine nursing practice in the field of HIV.

PMID- 22381080
TI  - Patient and visitor violence in the general hospital, occurrence, staff
      interventions and consequences: a cross-sectional survey.
AB  - AIM.: This study focuses on the experience of healthcare staff with regard to
      patient and visitor violence in a general hospital. The occurrence of patient and
      visitor violence, staffs' interventions and the consequences of violence for
      different professions are investigated. BACKGROUND: There is a lack of studies
      describing the factors influencing the occurrence of patient and visitor
      violence, intervention strategies and consequences. Existing studies often focus
      on nurses' experiences and single interactive factors between staff and
      patients/visitors involved. DESIGN: A cross-sectional survey. METHOD: The survey
      was conducted in 2007 including 2495 staff working on different wards in a Swiss
      university general hospital. The questionnaire used was the Survey of Violence
      Experienced by Staff German Version-Revised. FINDINGS: Half of the staff
      experienced patient and visitor violence in the past 12 months and 11% in the
      past week. The age of the staff and the length of experience in their present
      workplace influenced the exposure to patient and visitor violence. Violence
      occurred mainly when staff carried out tasks involving close personal contact.
      Only 16% of the staff was trained in aggression management. The feeling of
      confidence in managing patient and visitor violence depended significantly on the
      organizational attitude towards violence. The principal interventions used were
      calming and informative discussion. CONCLUSION: To prevent patient and visitor
      violence and improve management strategies, training which focuses on
      communication skills, which is specific to the professional context and which
      emphasizes patient centeredness, need to be designed and implemented. A strong
      organizational commitment is imperative to reduce violence.

PMID- 22381081
TI  - Multicomplex-based pharmacophore-guided 3D-QSAR studies of N-substituted 2'
      (aminoaryl)benzothiazoles as Aurora-A inhibitors.
AB  - Aurora-A has been known as one of the most important targets for cancer therapy,
      and some Aurora-A inhibitors have entered clinical trails. In this study,
      combination of the ligand-based and structure-based methods is used to clarify
      the essential quantitative structure-activity relationship of known Aurora-A
      inhibitors, and multicomplex-based pharmacophore-guided method has been suggested
      to generate a comprehensive pharmacophore of Aurora-A kinase based on a
      collection of crystal structures of Aurora-A-inhibitor complex. This model has
      been successfully used to identify the bioactive conformation and align 37
      structurally diverse N-substituted 2'-(aminoaryl)benzothiazoles derivatives. The
      quantitative structure-activity relationship analyses have been performed on
      these Aurora-A inhibitors based on multicomplex-based pharmacophore-guided
      alignment. These results may provide important information for further design and
      virtual screening of novel Aurora-A inhibitors.

PMID- 22381082
TI  - IgD multiple myeloma a descriptive report of 17 cases: survival and response to
      therapy.
AB  - BACKGROUND: Immunoglobulin D multiple myeloma (MM) is rare and has a poorer
      prognosis than other MM isotypes. DESIGN AND METHODS: Seventeen patients (pts)
      diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of
      Multiple Myeloma Latium-Region GIMEMA Working Group. RESULTS: Median age was 55
      years, 14 patients had bone lesions, eight had renal impairment with estimated
      glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium >= 12 mg/dl, 11
      had lambda light chains, five stage III of ISS, six with chromosomal
      abnormalities. Six pts received conventional chemotherapy (CT): five melphalan +
      steroids based regimens. Eleven underwent high-doses of chemotherapy with
      autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT:
      six received bortezomib and/or thalidomide as induction therapy and five VAD.
      Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group;
      bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38
      (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT,
      respectively, the overall response rate (ORR) was 83% and 90%. In the group of
      patients treated with CT, median overall survival (OS) was 34 months (95% CI 15-
      54 months), median progression free survival (PFS) was 18 months (95% CI 3-33
      months) and median duration of response (DOR) was 7 months (95% CI 5-9 months).
      Median OS, PFS and DOR were not reached at the time of this analysis in the
      HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with
      HDT/ASCT and in 66.7% undergone CT. CONCLUSIONS: Despite the retrospective
      analysis and the small number of pts our study showed that the use of HDT/ASCT
      seems to improve also the prognosis of IgD MM patients. Treatment options
      including new drugs, before and after stem cell transplantation, may further
      improve the outcomes of these patients.

PMID- 22381083
TI  - The role of procalcitonin in adult patients with community-acquired pneumonia--a
      systematic review.
AB  - INTRODUCTION: Promising results in relation to severity assessment and treatment
      of patients with community-acquired pneumonia (CAP) have recently been presented
      from the study of procalcitonin (PCT) levels in these patients. METHODS: A
      systematic search in PubMed and the Cochrane Library was conducted. Articles in
      English, German and Swedish were searched to investigate the role of PCT in
      adults with CAP. RESULTS: The most thoroughly studied topic is the prediction of
      complications and death during hospital stay. PCT has predictive properties
      comparable to those of the Pneumonia Severity Index and the CURB65 scoring
      systems, and it may represent an addition to these indices. Furthermore, PCT
      levels may indicate aetiology as patients with typical bacterial infection have
      higher PCT levels than patients with atypical and viral aetiologies. The
      literature also indicates that PCT can distinguish CAP from asthma and acute
      exacerbation of chronic obstructive pulmonary disease. Several studies and a meta
      analysis have shown that administration of antibiotics according to a PCT
      algorithm in a hospital setting reduced the use of antibiotics with no evidence
      of an increased risk. CONCLUSION: PCT should only be an adjunct to the clinical
      examination and should be regarded a prognostic rather than diagnostic factor.
      PCT may help to safely reduce anti-biotic use, but more research is required.
      Limitations of the present study include the heterogeneity of the literature with
      regard to setup and quality, differences in biochemical methods and diagnostic
      criteria of CAP and, finally, the risk of publication bias.

PMID- 22381084
TI  - Use of biological mesh in facilitation of early closure in potentially infected
      abdominal wall defects.
AB  - INTRODUCTION: Abdominal wall defects with exposed bowels present a significant
      risk of iatrogenic and spontaneous intestinal fistulation, and early wound
      closure is warranted. We describe our experience with the use of biological mesh
      (BM) for facilitation of secondary abdominal wall closure in patients with
      abdominal wall defects after severe complications, including surgically
      inaccessible enteric fistulas. MATERIAL AND METHODS: The present study is a
      prospective cohort study comprising ten patients with abdominal wall defects
      treated with BM. At reconstructive surgery with BM, six patients had stomas, four
      had wounds complicated by intestinal fistulas and three had both. RESULTS: In
      five cases, the abdominal wall was closed without complications. The remaining
      five patients had unsuccessful primary healing of the skin, but all subsequently
      healed by granulation on the mesh. In two cases, BM was implanted directly on
      exposed bowel with inaccessible fistulas still present. Patients were discharged
      a median of 15 days (6-35 days) after insertion of the BM. The median follow-up
      was 11 months (1.5-18.5 months). Only one patient developed a hernia. CONCLUSION:
      BM can be used in contaminated defects, even when primary skin closure is not
      achieved, or with fistulas still present causing continuous contamination of the
      surgical site and mesh. BM facilitates early closure of the abdomen. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 22381085
TI  - Authorship trends over the past fifty years in the Journal of the Danish Medical
      Association (Danish: Ugeskrift for Laeger).
AB  - INTRODUCTION: Internationally, the number of authors per scientific article is
      increasing. The objective of this study was to determine authorship trends over
      the past fifty years in Ugeskrift for Laeger (UfL). MATERIAL AND METHODS: From
      1960 to 2010, ten volumes of the UfL, 5,962 articles in total, were studied. For
      each article, category and number of authors were recorded. RESULTS: The median
      number of authors per article (all categories) was one in 1960 (range 1-3), two
      in 1985 (range 1-9) and three in 2010 (range 1-14). The proportion of articles
      published by three or more authors constituted 1% in 1960 and 68% in 2010. For
      original articles, the median number of authors per article was two in 1960
      (range 1-3), three in 1985 (range 1-9) and three in 2010 (range 1-9). For
      reviews, the median number of authors per article was one in 1960 (range 1-2),
      two in 1985 (range 1-5) and three in 2010 (range 1-14). For case reports, the
      median number of authors per article was one in 1960 (range 1-2), two in 1985
      (range 1-5) and three in 2010 (range 1-6). CONCLUSION: The number of authors per
      article increased for all types of articles published in the UfL. This could
      reflect increases in "gift authorship", but "multiple authorship" could also be
      fully legitimate. Replacing or supplementing authorship criteria with
      contribution statements would provide some transparency and accountability. Yet,
      questions about credit assessment and overall responsibility need to be
      clarified. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22381086
TI  - Validation of hospital register-based diagnosis of Parkinson's disease.
AB  - INTRODUCTION: Denmark has a long-standing tradition of maintaining one of the
      world's largest health science specialized register data bases as the National
      Hospital Register (NHR). To estimate the prevalence and incidence of diseases,
      the correctness of the diagnoses recorded is critical. Parkinson's disease (PD)
      is a neurodegenerative disorder and only 75-80% of patients with parkinsonism
      will have idiopathic PD (iPD). It is necessary to follow patients in order to
      determine if some of them will develop other neurodegenerative diseases and a one
      time-only diagnostic code for iPD reported in the register may be incorrect.
      MATERIAL AND METHODS: This was a large nationwide population-based study of risk
      factors for iPD, called Parkinson's disease in Denmark (PASIDA). We evaluated the
      iPD diagnosis reported in the NHR. Medical records with primary diagnoses of iPD
      from six neurological departments were collected and abstracted using a
      standardized system to review the diagnostic accuracy of the ICD codes. RESULTS:
      Among the 1,040 medical records abstracted, 857 (82.4%) patients met our criteria
      for iPD. 183(17.6%) of the patients suffered from other diagnoses such as
      atypical PD (66 patients), secondary PD (60 patients) and other diagnoses (46
      patients). CONCLUSION: Possibly only about 82% of the patients with the primary
      diagnosis of iPD in the Danish NHR actually suffered from iPD. To improve
      diagnostic validity, we appeal to update the ICD code and to identify the correct
      parkinsonian phenotype to reduce biased case sampling in register-based studies
      and appropriate treatment for these rare diseases. FUNDING: This study was
      supported by a grant from the National Institutes of Environmental Health
      Sciences, USA (grant No R01 ES013717). The funding source had no role in the
      design or analysis of the study or in the decision to submit the manuscript for
      publication. TRIAL REGISTRATION: Ethical approval: The study protocol was
      approved by the Danish Data Protection Agency (No 2006-41-7323) and by UCLA-IRB.

PMID- 22381087
TI  - Improved education after implementation of the Danish postgraduate medical
      training reform.
AB  - INTRODUCTION: A reform of educational postgraduate medical training was launched
      in Denmark in 2004. The reform was based on a report by the Danish Medical
      Specialist Commission and consisted of a number of initiatives that were all
      aimed at improving the quality of medical training. Since 1998, all junior
      doctors in Denmark have been requested to rate the quality of their training on a
      Danish standardized questionnaire (DSQ) comprising 24 questions. In this study,
      we examined how junior doctors in hospitals rated their postgraduate medical
      training before and six years after the reform was implemented. MATERIAL AND
      METHODS: This study is a cross-sectional register study of DSQ ratings of the
      postgraduate training in the region of Southern Denmark in 2002-2004 and in 2010.
      The ratings were extracted from the official database: www.evaluer.dk. RESULTS:
      For comparison, a total of 1,028 ratings from before the reform and 686 ratings
      from after the reform were extracted. 70% of junior doctors filled in a DSQ in
      2010. The doctors' perceptions of the training improved from 2002-2004 to 2010 as
      far as educational outcome and the department's educational effort were
      concerned. However, no change was evident in several questions targeting
      educational management. CONCLUSION: Based on the junior doctors' DSQ ratings, the
      quality of postgraduate training has improved in several areas from 2002-2004 to
      2010. But there is still room for improvement. Developing a new, validated
      questionnaire should be considered in order to ensure a high credibility in
      future work on quality.o. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22381088
TI  - Effective treatment at a Danish trauma centre.
AB  - INTRODUCTION: The trauma centre at Aarhus University Hospital, Denmark was
      established in 1999 and has continuously tried to improve its efficiency through
      regular training of personnel and auditing of selected trauma cases. The purpose
      of the present study was to assess the efficiency of the trauma teams to perform
      the initial evaluation using the time spent in the emergency room after arrival
      and the time to the first chest X-ray as measures for effectiveness. MATERIAL AND
      METHODS: This was a prospective cohort study conducted from January 2000 to
      December 2008 and which included all trauma patients admitted to the hospital.
      RESULTS: The results are based on 4,493 admissions, of which 1,102 patients (24%)
      had an injury severity score > 15. The median time spent in the trauma room was
      50 minutes in 2000, which was steadily reduced throughout the period reaching a
      median time of 27 minutes in 2008 (p < 0.0001, Kruskal-Wallis test). The median
      time to the first chest X-ray was reduced from seven minutes in 2001 to five
      minutes in 2008 (p < 0.024, Kruskal-Wallis test). CONCLUSION: Utilisation of a
      standardised protocol for initial evaluation and treatment of trauma patients and
      continuous training of trauma teams may considered some of the main factors
      responsible for these findings. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22381089
TI  - Social inequalities in childhood are predictors of unemployment in early
      adulthood.
AB  - INTRODUCTION: The aim of the present study was to establish if social
      inequalities in early childhood, particularly living in a socially and
      economically deprived neighbourhood, are predictive of later unemployment.
      MATERIAL AND METHODS: A cohort was established in 1987. It consists of 8-9 year
      old children living in a socially deprived suburb who were followed in national
      registers for all categories of welfare benefits. The follow-up covered the
      period when participants were 21-27 years of age. A control group with the same
      age and gender distribution who were living in a neighbouring, relatively
      privileged middle class district were also followed for the purpose of
      comparison. RESULTS: The annual unemployment rate during the seven years of
      follow-up was significantly higher in the deprived neighbourhood group than in
      the middle class neighbourhood group, whereas long-term unemployment lasting more
      than two years did not differ significantly between the groups. Childhood
      background including a mother receiving social benefit was an independent factor
      associated with increased risk of later unemployment, whereas gender and single
      parenthood were not. CONCLUSION: The present findings suggest that socioeconomic
      disadvantage during childhood substantially increases the risk of unemployment in
      early adulthood, even during a follow-up period in the first decade of the 21st
      century when employment opportunities in Denmark were excellent. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 22381090
TI  - Intensive care of haematological patients.
AB  - INTRODUCTION: This article presents the treatment results of 320 consecutive
      patients with malignant haematological diagnoses admitted to a tertiary intensive
      care unit at a Danish University hospital over a six-year period (2005-2010).
      With reference to international publications, we describe the development in
      treatment. MATERIAL AND METHODS: This was a retrospective observational study.
      RESULTS: The median age was 59 years. The median intensive care unit (ICU) stay
      was six days. A total of 88% required mechanical ventilation, and 72% received
      vasopressor treatment. The median Simplified Acute Physiology Score II score was
      58. The ICU and one-year mortality rates were 44% and 77%, respectively, but
      mortality was significantly lower for patients aged 0-20 years. For patients aged
      20-80 years, the mortality risk was independent of age. For the group of patients
      admitted acutely to the ICU with other diagnoses, the ICU- and the one-year
      mortality rate was 13% and 33%, respectively. CONCLUSION: Despite progress, the
      mortality rate for haematological patients in ICUs is high. We lack valid tools
      that allow us to differentiate between those who can benefit from intensive care
      and those for whom transfer to an ICU is futile. One patient out of five is alive
      after one year. This supports a strategy offering haematological patients
      intensive care on an equal footing with other patients. Follow-up studies of
      survivors,  clarification of function level and quality of life are needed.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22381091
TI  - Systemic mastocytosis--a systematic review.
AB  - INTRODUCTION: The mast cell lives a hidden life, but it is implicated in several
      physiological reactions. Its ability to react to different stimuli impacts a
      variety of conditions such as asthma, atopic dermatitis, urticaria and
      anaphylaxis. It is not until recent decades that the evolution of the cell has
      been described and its fascinating biology has only recently been depicted. We
      here give a review of systemic mastocytosis in regards to cell biology,
      diagnostic approaches and clinical practice. METHODS: A search was made in PubMed
      in August 2011 entering the keywords: mastocytosis, (systemic, cutaneous,
      aggressive), mast cell leukaemia, mast cell sarcoma, chromosome, mutation,
      haematology and treatment. RESULTS: Mastocytosis is characterized by an abnormal
      proliferation of mast cells, which accumulate in one or several organ systems,
      primarily the skin and bone marrow. The disease is clinically heterogeneous and
      varies from a relatively benign condition with isolated cutaneous lesions to a
      very aggressive systemic condition with a grave prognosis. The condition affects
      men and women equally. Children are especially affected by the cutaneous form. In
      most children, the condition will improve or remit spontaneously before
      adulthood. Mastocytosis in adults, however, is more often systemic and tends to
      persist. CONCLUSION: Patients with mastocytosis represent a heterogeneous group
      in terms of clinical presentation, management and prognosis. Furthermore, a range
      of medical specialties serve as the primary entrance to health services, which
      can be a challenge in respect of achieving uniform management. In order to
      improve diagnostics and management of systemic mastocytosis, the European
      Competence Network on Mastocytosis has been established. Patients under suspicion
      of systemic mastocytosis should be conferred with or referred to a haematological
      and a dermatological/allergological department.

PMID- 22381092
TI  - Effective dermatomal blockade after subcostal transversus abdominis plane block.
AB  - INTRODUCTION: The ultrasound-guided transversus abdominis plane (TAP) block is
      used to treat postoperative pain after abdominal surgery. Abdominal wall sensory
      nerves are anaesthetised by injecting local anaesthetics into the neurofascial
      plane between the internal oblique and the transversus abdominis muscles. Sensory
      assessment of a TAP block may guide the decision on the extent of the block. The
      purpose of this study was to investigate if the dermatomal extent of sensory
      blockade after injection of 20 ml 0.5% ropivacaine bilaterally into the TAP can
      be assessed using cold and pinprick sensation. MATERIAL AND METHODS: Subcostal
      TAP block was performed bilaterally in 20 awake patients scheduled for elective
      abdominal surgery. Sensory change in dermatomes T4-L4 was tested with pinprick
      using a blunt needle and cold disinfectant swabs after 10, 20 and 30 minutes.
      RESULTS: Data from 20 patients (40 blocks) were analysed. Eighteen patients
      registered sensory change after subcostal TAP block, and dermatomes T10-T12 were
      blocked after 30 minutes in all of these patients. Spread of sensory change to
      dermatomes T5-L3 was variable. CONCLUSION: This study confirmed that the
      dermatomal extent of a sensory blockade after a single-shot subcostal TAP block
      can be assessed using cold and pinprick sensation. FUNDING: not relevant. TRIAL
      REGISTRATION: The study was registered at clinicaltrials.gov with the
      registration number NCT01024868.

PMID- 22381093
TI  - Assessment of right ventricular systolic function by tissue Doppler
      echocardiography.
AB  - This thesis summarizes a series of studies performed in order to assess the
      clinical usefulness of a novel echocardiographic technology that allows non
      invasive assessment of regional right ventricular myocardial velocities and
      deformation: tissue Doppler echocardiography. While the technology is a promising
      tool for improving our understanding of right ventricular hemodynamics, several
      aspects of the technology must be evaluated. The accuracy and reproducibility of
      the technology is evaluated in vitro, and normal values, impact of changes in
      loading of the right ventricle, response to exercise and pharmacological
      pulmonary vasodilatation is established in normal subjects. The diagnostic and
      prognostic importance of adding tissue Doppler echocardiography to conventional
      echocardiographic and clinical parameters was evaluated in studies on patients
      with diseases associated with different modes of impact on right ventricular
      hemodynamics: pulmonary embolism, Arrhythmogenic right ventricular cardiomyopathy
      and pulmonary regurgitation, the latter in an animal model.  The conclusions of
      the thesis are:  Color tissue Doppler echocardiography accurately measures
      velocities, SR and strain in vitro. No systematic bias between ultrasound systems
      can be found, and accuracy of the measurements is good. However, the
      reproducibility of measurements in a test-retest design can limit the usefulness
      of the technology in daily clinical use, as 25% to 80% of change would be needed
      for the technology to identify a change in individual patients [I].  Normal
      values of tissue Doppler based measurements of RV regional velocities, SR and
      strain exist, and apply to both sexes and in all age groups with the exception of
      slightly decreasing values in strain with increasing age. Increasing preload and
      afterload changes regional myocardial velocities, but no changes in SR, strain or
      isovolumic acceleration could be observed [II and III].  Tissue Doppler
      echocardiography of the RV free wall in non-massive pulmonary embolism quantifies
      degree of RV dysfunction, and supports the existence of the McConnell sign of mid
      ventricular RV dysfunction. Echocardiographic signs of RV dysfunction are present
      if > 25% of the pulmonary vascular bed is obstructed. However, Tissue Doppler
      echocardiography and deformation analysis has no independent value over other
      clinical and quantitative echocardiographic measures of RV size, pressure and
      function in these patients [IV and V].  Regional deformation of the RV free wall
      has significant prognostic importance in a population suspected of first non
      massive pulmonary embolism, and is significantly associated with adverse events
      in patients with proven pulmonary embolism, however, it does not add to the
      information gained from other quantitative echocardiographic measures of LV and
      RV function and pressure [VI].  Changes in tissue Doppler based measures of RV
      systolic function can be used to monitor the effect of selective vasodilation by
      phosphodiestares-5 inhibition in hypoxic pulmonary hypertension and exercise in
      normal individuals. Phosphodiestares-5 inhibition by sildenafil may predominantly
      be effective during hypoxia in resting conditions, and may improve the blunted
      response in RV contractility seen with exercise in hypoxia [VII].  Reduced RV
      free wall deformation can be quantified by tissue Doppler echocardiography in
      patients with confirmed Arrhythmogenic Right Ventricular Cardiomyopathy, but the
      clinical application of the technique may be limited by considerable overlap with
      normal values [VIII].  Acute RV volume loading in free pulmonary regurgitation is
      associated with abrupt geometric changes in the RV structure including
      significant dilatation, but is well tolerated with only mild reduction in
      measures of global RV systolic function as estimated by 2D echocardiography in an
      experimental animal model. Regional RV myocardial function is also only mildly
      reduced. Also no differences in global or regional RV function can be observed
      after 1-3 months of pulmonary regurgitation [IX and X].  Relief of free pulmonary
      regurgitation by percutaneus pulmonary valve replacement in an animal model is
      associated with immediate reverse remodeling of the RV. No changes in tissue
      Doppler based measures of RV contractility can be identified [X].

PMID- 22381094
TI  - Granulocyte-colony stimulating factor therapy to induce neovascularization in
      ischemic heart disease.
AB  - Cell based therapy for ischemic heart disease has the potential to reduce post
      infarct heart failure and chronic ischemia. Treatment with granulocyte-colony
      stimulating factor (G-CSF) mobilizes cells from the bone marrow to the peripheral
      blood. Some of these cells are putative stem or progenitor cells. G-CSF is
      injected subcutaneously. This therapy is intuitively attractive compared to other
      cell based techniques since repeated catheterizations and ex vivo cell
      purification and expansion are avoided. Previous preclinical and early clinical
      trials have indicated that treatment with G-CSF leads to improved myocardial
      perfusion and function in acute or chronic ischemic heart disease. The hypothesis
      of this thesis is that patient with ischemic heart disease will benefit from G
      CSF therapy. We examined this hypothesis in two clinical trials with G-CSF
      treatment to patients with either acute myocardial infarction or severe chronic
      ischemic heart disease. In addition, we assed a number of factors that could
      potentially affect the effect of cell based therapy. Finally, we intended to
      develop a method for in vivo cell tracking in the heart. Our research showed that
      subcutaneous G-CSF along with gene therapy do not improve myocardial function in
      patients with chronic ischemia despite a large increase in circulation bone
      marrow-derived cells. Also, neither angina pectoris nor exercise capacity was
      improved compared to placebo treatment. We could not identify differences in
      angiogenic factors or bone marrow-derived cells in the blood that could explain
      the neutral effect of G-CSF. Next, we examined G-CSF as adjunctive therapy
      following ST segment elevation myocardial infarction. We did not find any effect
      of G-CSF neither on the primary endpoint--regional myocardial function--nor on
      left ventricular ejection fraction (secondary endpoint) compared to placebo
      treatment. In subsequent analyses, we found significant differences in the types
      of cells mobilized from the bone marrow by G-CSF. This could explain why
      intracoronary injections of unfractionated bone marrow-derived cells have more
      effect that mobilization with G-CSF. A number of other factors could explain the
      neutral effect of G-CSF in our trial compared to previous studies. These factors
      include timing of the treatment, G-CSF dose, and study population. It is however,
      remarkable that the changes in our G-CSF group are comparable to the results of
      previous non-blinded studies, whereas the major differences are in the
      control/placebo groups. We found that ejection fraction, wall motion, edema,
      perfusion, and infarct size all improve significantly in the first month
      following ST-segment myocardial infarction with standard guideline treatment
      (including acute mechanical revascularization), but without cell therapy. This is
      an important factor to take into account when assessing the results of non
      controlled trials. Finally, we found that ex vivo labeling of cells with indium
      111 for in vivo cell tracking after intramyocardial injection is problematic. In
      our hand, a significant amount of indium-111 remained in the myocardium despite
      cell death. It is difficult to determine viability of the cells after injection
      in human trials, and it is thus complicated to determine if the activity in the
      myocardium tracks viable cells. Cell based therapy is still in the explorative
      phase, but based on the intense research within this field it is our hope that
      the clinical relevance of the therapy can be determined in the foreseeable
      future. Ultimately, this will require large randomized, double-blind and placebo
      controlled trials with "hard" clinical endpoints like mortality and morbidity.

PMID- 22381095
TI  - Urethral pressure reflectometry. A method for simultaneous measurements of
      pressure and cross-sectional area in the female urethra.
AB  - A novel technique for simultaneous measurements of pressure and cross-sectional
      area (CA) in the female urethra, denoted Urethral Pressure Reflectometry (UPR),
      was devised. A very thin and highly flexible polyurethane-bag was placed in the
      urethra. A pump applied increasing and decreasing pressures to the polyurethane
      bag and thereby opened and closed the urethra. Sound waves were continually sent
      into the polyurethane-bag and the cross-sectional area (CA) of the bag (urethra)
      could be measured from the reflections with Acoustic Reflectometry. The CA of the
      bag was measured for each mm of the bag and 10 times per second. The examinations
      were performed with the women supine relaxing, supine squeezing, and standing
      relaxing. The examination provided measures of the opening pressure (the pressure
      exactly needed to open the urethra), the closing pressure (the pressure where the
      urethra closes again after dilation), the opening elastance (the resistance
      against dilation), the closing elastance (urethras ability to close again after
      dilation) and the hysteresis (the energy which dissipates when urethra is
      dilated).  The examination was reliable both in vitro and in vivo. All the UPR
      parameters except the hysteresis were decreased in stress urinary incontinent
      (SUI) women compared to continent women. Thus the parameters seem to be relevant
      regarding SUI. UPR examination was performed before and after urethral bulking
      and from these examinations a mechanism of action of the bulking procedure was
      proposed. A randomised, double-blinded placebo-controlled cross-over study
      demonstrated that UPR is valuable in developing and monitoring pharmacological
      treatments for SUI. Cases demonstrated that UPR has potential to sub-classify SUI
      in accordance to the patophysiology and establish pathological conditions i.e. a
      stricture.

PMID- 22381096
TI  - The ECG as decision support in STEMI.
AB  - The electrocardiogram (ECG) can be used for determining the presence, location
      and extent of jeopardized myocardium during acute coronary occlusion.
      Accordingly, the ECG has become essential in the treatment of patients with acute
      coronary syndrome (ACS). This thesis aims at optimizing the decision support,
      provided by the ECG, for choosing the best treatment strategy in the individual
      patient with ST-segment elevation acute myocardial infarction (STEMI).  ECG
      recorded in the prehospital setting has become the standard of care in many
      communities, but to achieve the full advantage of this early approach it is
      important that the ECG is recorded from accurately placed electrodes to produce
      an ECG that resembles the standard 12-lead ECG. Accurate electrode placement is
      difficult especially in the acute setting, and we investigated an alternative
      lead system with fewer electrodes in easily identified positions. We showed that
      the system produced waveforms similar to the standard 12-lead ECG. However,
      occasional diagnostic errors were seen, compromising general acceptance of the
      system.   Once the ECG has been recorded a decision regarding triage must be made
      on the basis of a correct ECG diagnosis. We found that trained paramedics can
      diagnose STEMI correctly in patients without ECG confounding factors, while the
      presence of ECG confounding factors decreased their ability substantially.
      Consequently, since many patients do present with ECG confounding factors,
      transmission to an on-call cardiologist for an early correct diagnosis is needed.
      We showed that time to pPCI was reduced by more than 1 hour by transmitting
      prehospital ECG to a cardiologist's handheld device for diagnosis, triage, and
      activation of the catheterization laboratory when needed.   The optimal treatment
      strategy is dependent on the duration of ischemia however patient information is
      often inaccurate. Accordingly, it would be advantageous if the first available
      ECG can help identify patients who will benefit greatly from acute reperfusion
      therapy versus patients with modest effect. We showed that by recognizing the
      acuteness of the infarction process the initial ECG can identify a group of
      patients with no potential for myocardial salvage despite short symptom duration.
      Urgent transport for pPCI may then not be necessary in this group of patients,
      and conservative treatment may be an option. Conversely, we also identified a
      group of patients with a large potential for myocardial salvage with acute
      reperfusion therapy despite long symptom duration.   We also investigated whether
      ST-segment elevation on the initial ECG could provide prognostic information and
      thereby decision support for appropriate triage. All patients regardless of ST
      segment elevation seemed to have most clinical benefit from pPCI. However, only
      patients with the greatest amount of ST-segment elevation had a reduced mortality
      rate with pPCI suggesting that patients with minor infarcts may achieve similar
      benefit from fibrinolysis followed by transfer to angiography and PCI.   Once the
      triage decision is settled, STEMI patients must undergo ECG monitoring and
      receive antithrombotic therapy for optimal prehospital care. STEMI patients
      transported over even short distances are in danger of developing arrhythmic
      complications, but appropriate treatment is available when primary ambulances are
      supported by physician-manned ambulances in urban areas. Prehospital
      antithrombotic therapy must be effective in preparing the patient for pPCI
      without causing bleeding. Heparin is currently the standard therapy, but we
      showed that the direct thrombin inhibitor bivalirudin may be an attractive
      alternative by causing less bleeding events, and a higher frequency of
      preprocedure thrombolysis in myocardial infarction (TIMI) 3 flow.   After
      reperfusion therapy a decision regarding the need for further treatment is
      desirable. By determining ST-segment resolution in the post-reperfusion ECG we
      showed that the degree of ST-segment resolution at 90 minutes and 4 hours is
      important for risk stratification after fibrinolysis, but not after pPCI.
      Interestingly, we found that patients with compete ST-segment resolution treated
      with fibrinolysis had the highest risk of reinfarction. Consequently, transfer to
      a PCI-facility should be considered in all patients treated with fibrinolysis as
      the initial reperfusion therapy.   Based on the findings in the present thesis we
      conclude that the ECG is an important tool for decision support in every step
      from symptom onset to post-reperfusion therapy in STEMI patients.

PMID- 22381097
TI  - Postoperative non-steroidal anti-inflammatory drugs and colorectal anastomotic
      leakage. NSAIDs and anastomotic leakage.
AB  - Anastomotic leakage (AL) is the most important and one of the most serious
      complications after colorectal resections with primary anastomosis. Any factors
      that contribute to increase the risk of AL should be identified and--if possible-
      eliminated. Non-steroidal anti-inflammatory drugs (NSAIDs) are often used for
      treating pain after surgical procedures, among these also colorectal resections.
      The objective of this Ph.d. thesis was to investigate whether the use of NSAIDs
      in the postoperative period increases the risk of AL, and investigate the effect
      on pathophysiological mechanisms. In order to achieve this, the following studies
      were performed. Study I was a retrospective, case-control study in 75 patients
      undergoing laparoscopic colorectal resection for colorectal cancer. 33 of these
      patients received the NSAID diclofenac in the postoperative period; the remaining
      42 did not receive any NSAID. There were significantly more ALs among the
      patients receiving diclofenac (7/33 vs. 1/42, p=0.018). In uni- and multivariate
      logistic regression analyses, diclofenac was the only factor associated with
      increased AL rate. This study functioned as a hypothesis generating study and
      laid the ground for the subsequent studies. Study II was an experimental,
      randomized, case-control study in 32 Wistar rats. The rats had a colonic
      anastomosis performed and were randomized to diclofenac or placebo treatment.
      After three days, the rats were sacrificed and the anastomoses were harvested.
      First, the anastomotic strengths were tested by longitudinal; subsequently, the
      levels of the enzyme cyclooxygenase-2 (COX-2) in the anastomotic tissues were
      measured. There was no difference among the groups with regard to anastomotic
      strength, but the animals treated with diclofenac had significantly lower COX-2
      levels (median (range) 1.30 (0.42-3.31) ng/mg vs. 2.44 (0.88 - 18.94) ng/mg,
      p<0.001). This study showed that the used dose of diclofenac was sufficient and
      relevant, but did not show a direct damaging effect on the anastomoses due to
      NSAID treatment. Study III was also an experimental, randomized, case-control
      study. This time round, 60 Wistar rats were included. Again, colonic anastomoses
      were performed and the rats were randomized to diclofenac or placebo. Also,
      expanded polytetrafluoruethylene (ePTFE) tubes were placed under the skin of the
      rats. In this material, substituents of connective tissue accumulate and the
      amount of accumulation can be measured. After 7 days, the rats were sacrificed
      and, again, anastomotic strengths were measured along with collagen content in
      the ePTFE tubes. Anastomotic strength was similar in the two groups while
      collagen accumulation was significantly decreased among the rats treated with
      diclofenac (median (i.q.r.) 0.29 (0.13-0.47) vs. 0.47 (0.28-0.62) mcg/mg, p =
      0.03). This study for the first time showed that NSAID inhibit subcutaneous
      collagen formation and that this formation is reversely correlated to anastomotic
      strength. This information can be used in further studies in this subject. Study
      IV was the final experimental case-control study in 40 Wistar rats. This time, in
      order to more easily extrapolate experimental results to daily clinical life, the
      colonic anastomoses were sutured with the same type of suture material as used in
      the clinical setting. Thus, half the anastomoses was performed with resorbable
      suture; the other half with non-resorbable suture. None of the rats received
      NSAID. The breaking strength was compared and found similar in the two groups.
      This study showed that experimental studies can be optimized in order to make
      comparisons and extrapolations to the clinical setting easier. Study V was a
      database study based on data from the Danish Colorectal Cancer Group's (DCCG)
      prospective database and electronically registered medical records. From the
      database information on demographic, surgical and postoperative variables
      (including AL) were provided. Information on NSAID consumption was retrieved by
      individual searches in the patients' medical records. Based on these data, uni-
      and multivariate logistic regression analyses were performed. These analyses
      identified NSAID treatment in the postoperative period as an individual risk
      factor for AL. Other risk factors identified were consistent with the available
      literature. The detrimental effect of the NSAIDs are possibly due to an effect on
      collagen metabolism leading to weakened tissue around the anastomosis and/or on
      the risk of thrombosis formation leading to more thromboses in the vessels
      supplying the anastomosis, thereby limiting anastomotic blood flow. In
      conclusion, the studies included in this thesis have elucidated some of the
      physiological and pathophysiological mechanisms involved in anastomotic healing
      and leakage, and furthermore have shown that the use of NSAIDs in the
      postoperative period increase the risk of AL in patients undergoing colorectal
      surgery with primary anastomosis. Based on the findings in these studies, and
      based on existing knowledge, it is recommended that NSAIDs be abandoned after
      colorectal resection with primary anastomosis. It should be investigated whether
      the NSAIDs are also harmful to other types of anastomoses and after other
      surgical procedures where early tissue healing is crucial.

PMID- 22381098
TI  - Proprioceptive information processing in schizophrenia.
AB  - This doctoral thesis focuses on brain activity in response to proprioceptive
      stimulation in schizophrenia. The works encompass methodological developments
      substantiated by investigations of healthy volunteers and two clinical studies of
      schizophrenia spectrum patients.   American psychiatrist Sandor Rado (1890-1972)
      suggested that one of two un-reducible deficits in schizophrenia was a disorder
      of proprioception. Exploration of proprioceptive information processing is
      possible through the measurement of evoked and event related potentials. Event
      related EEG can be analyzed as conventional time-series averages or as
      oscillatory averages transformed into the frequency domain.  Gamma activity
      evoked by electricity or by another type of somatosensory stimulus has not been
      reported before in schizophrenia. Gamma activity is considered to be a
      manifestation of perceptual integration.  A new load stimulus was constructed
      that stimulated the proprioceptive dimension of recognition of applied force.
      This load stimulus was tested both in simple and several types of more complex
      stimulus paradigms, with and without tasks, in total in 66 healthy volunteers.
      The evoked potential (EP) resulting from the load stimulus was named the
      proprioceptive EP. The later components of the proprioceptive EP (> 150 ms) were
      modulated similarly to previously reported electrical somatosensory EPs by
      repetition and cognitive task. The earlier activity was further investigated
      through decomposition of the time-frequency transformed data by a new non
      negative matrix analysis, and previous research and visual inspection validated
      these results.   Several time-frequency components emerged in the proprioceptive
      EP. The contra-lateral parietal gamma component (60-70 ms; 30-41 Hz) had not
      previously been described in the somatosensory modality without electrical
      stimulation. The parietal beta component (87-103 ms; 19-22 Hz) was increased when
      the proprioceptive stimulus appeared in a predictable sequence in several runs of
      recording. Although the experimental paradigm had inherent confounders, it was
      suggested that the increase observed in the predictable situation, in healthy
      subjects, was due to priming of the somatosensory cortex through top-down
      modulation.    The proprioceptive EP was investigated in two different samples of
      a total of 30 schizophrenia spectrum patients. The left contra-lateral parietal
      cortical activity 60-120 ms following the load stimulus was affected in both
      samples. In the first experiment a delay was observed and in the second
      experiment diminished amplitude and trial-to-trial phase consistency of high
      frequency (18-45 Hz) activity.  Both effects were interpreted as a consequence of
      diminished precision of activation of the left somatosensory cortex and it was
      suggested to be in accordance with two theories of schizophrenic information
      processing: the theory of deficiency of corollary discharge and the theory of
      weakening of the influence of past regularities. No gating deficiency was
      observed and the imprecision and amplitude attenuation was not a general
      phenomenon across the entire brain response.  Summing up, in support of Rado's
      hypothesis, schizophrenia spectrum patients demonstrated abnormalities in
      proprioceptive information processing. Future work needs to extend the findings
      in larger un-medicated, non-chronic, patient samples and investigate the
      connection between schizophrenic symptoms, perception and attenuation of the
      proprioceptive EP.

PMID- 22381099
TI  - Effects of emotional stimuli on working memory processes in male criminal
      offenders with borderline and antisocial personality disorder.
AB  - OBJECTIVE. In the present study, we aimed to investigate the influence of
      concurrently presented emotional stimuli on cognitive task processing in violent
      criminal offenders primarily characterized by affective instability. METHODS.
      Fifteen male criminal offenders with antisocial and borderline personality
      disorder (ASPD and BPD) and 17 healthy controls underwent functional magnetic
      resonance imaging (fMRI) while performing a working memory task with low and high
      working memory load. In a second experimental run, to investigate the interaction
      of emotion and cognition, we presented emotionally neutral, low, or high salient
      social scenes in the background of the task. RESULTS. During the memory task
      without pictures, both groups did not differ in general task performance and
      neural representation of working memory processes. During the memory task with
      emotional background pictures, however, ASPD-BPD subjects compared to healthy
      controls showed delayed responses and enhanced activation of the left amygdala in
      the presence of emotionally high salient pictures independent of working memory
      load. CONCLUSIONS. These results illustrate an interaction of emotion and
      cognition in affective instable individuals with enhanced reactivity to
      emotionally salient stimuli which might be an important factor regarding the
      understanding of aggressive and violent behaviour in these individuals.

PMID- 22381100
TI  - Diarylindenotetracenes via a selective cross-coupling/C-H functionalization:
      electron donors for organic photovoltaic cells.
AB  - A direct synthesis of new donor materials for organic photovoltaic cells is
      reported. Diaryindenotetracenes were synthesized utilizing a Kumada-Tamao-Corriu
      cross-coupling of peri-substituted tetrachlorotetracene with spontaneous indene
      annulation via C-H activation. Vacuum deposited planar heterojunction organic
      photovoltaic cells incorporating these molecules as electron donors exhibit power
      conversion efficiencies exceeding 1.5% with open-circuit voltages ranging from
      0.7 to 1.1 V when coupled with C(60) as an electron acceptor.

PMID- 22381101
TI  - Angiotensin II receptor antagonist reduces subsequent uterine arterial
      dysfunction in pregnant offspring of protein-restricted rat dams.
AB  - AIM: A low-protein diet (LPD) during pregnancy induces vascular dysfunction and
      hypertension in the offspring, prevented by administration of an angiotensin II
      type 1 (AT(1)) receptor antagonist in early life to the offspring. Whether such
      protection extends to subsequent pregnancy is unknown; we therefore hypothesized
      that administration of a specific AT(1) receptor antagonist (losartan) in early
      life to offspring of LPD dams would improve vascular dysfunction in their uterine
      arteries when they, in turn, were pregnant. METHODS: Pregnant rats were randomly
      divided into two dietary groups fed a control (C) or protein-restricted (R) diet
      throughout pregnancy. Between two and 10 weeks postnatally, female offspring
      (F(1)) were randomly assigned to drink either pure tap water (CO, RO) or water
      with losartan (CL, RL). Offspring were mated and killed on gestational day 19 or
      20 in order to investigate uterine artery function. RESULTS: In pregnant
      offspring, vasoconstriction of the uterine arteries to phenylephrine (PE) and the
      thromboxane A2 mimetic U46619 was greater in RO than CO (F(1)). Responses to both
      antagonists were suppressed in RL (F(1)). Relaxation to sodium nitroprusside was
      increased in RO versus CO and suppressed in RL versus RO (F(1)). CONCLUSION:
      Administration of an AT(1) receptor antagonist to offspring during the suckling
      and juvenile period improves the uterine vascular dysfunction in pregnancy
      induced by prior maternal LPD during their development. Such treatment may
      contribute to decreasing the transmitted risks of maternal malnutrition from
      offspring to the subsequent generation.

PMID- 22381102
TI  - Effects of preeclampsia on the yield of hematopoietic stem cells obtained from
      umbilical cord blood at delivery.
AB  - AIM: To compare the numbers of cord blood CD34(+) hematopoietic stem cells (HSC)
      between preeclampsia (PE) and control (non-PE) subjects and to determine the
      factors that may influence this observation. METHODS: Umbilical cord blood was
      collected from 28 PE and 19 non-PE subjects. Nucleated and CD34(+) cell counts
      were derived using the Trucount tube-based stem cell enumeration kit on BD
      FACSCalibur. RESULTS: The cord blood volume, nucleated and CD34(+) cell counts
      were significantly reduced in PE subjects compared to non-PE subjects. Among the
      PE subjects, systolic and diastolic blood pressure demonstrated a negative
      correlation with total nucleated and CD34(+) cell counts. Gestational age at
      delivery influenced cord blood volume and nucleated cell counts, but not CD34(+)
      cell counts. Birth weight and placental weight correlated strongly with cord
      blood volume, and nucleated and CD34(+) cell counts. There were no correlations
      observed between cord blood parameters and maternal age, maternal white cell
      count, gravidity, route of delivery or neonatal gender among PE subjects.
      CONCLUSION: Preeclampsia has a negative impact on the yield of HSC obtained from
      cord blood at delivery. Maternal blood pressure, neonatal birth weight and
      placental weight are important factors influencing the numbers of cord blood HSC.
      These findings should be taken into consideration when selecting cord blood units
      from mothers with PE for banking. Selecting the heaviest term neonate might
      improve the yield of cord blood HSC obtained from PE mothers.

PMID- 22381103
TI  - Effects of 17beta-estradiol on the release of monocyte chemotactic protein-1 and
      MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis
      patients.
AB  - AIM: Hormones and inflammation have been implicated in the pathological process
      of endometriosis; therefore, we investigated the combined effects of 17beta
      estradiol (E2) and peritoneal fluid obtained from patients with endometriosis
      (ePF) or a control peritoneal fluid (cPF) obtained from patients without
      endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by
      monocytes and the role of signaling pathways. METHODS: Monocytes were cultured
      with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were
      then measured by ELISA. In addition, mitogen activated protein kinase (MAPK)
      activation was measured by Western blotting of phosphorylated proteins. RESULTS:
      E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes,
      but failed to suppress its release by ePF-treated monocytes. The release of MCP-1
      by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen
      activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF
      treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase
      inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular
      stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2
      decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated
      monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK
      in cPF-treated monocytes. CONCLUSIONS: The ability of E2 to modulate MCP-1
      production is impaired in ePF-treated monocytes, which may be related to
      regulation of MAPK activity. These findings suggest that the failure of E2 to
      suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of
      endometriosis.

PMID- 22381104
TI  - Abdominal wall endometriosis in the cesarean section surgical scar: a potential
      diagnostic pitfall.
AB  - AIM: The abdominal wall is an uncommon site of extrapelvic endometriosis. It
      usually develops in a previous surgical scar and should be considered in the
      differential diagnosis of any abdominal swelling. Classical symptoms of
      endometriosis may resemble abdominal wall lesions such as an incisional hernia,
      hematoma, granuloma, abscess or various soft tissue tumors; therefore, a
      definitive preoperative diagnosis is not always easy to determine in every case.
      The aim of this article is to review the clinical findings, imaging results and
      histopathology of those of our patients who have had cesarean scar endometriosis.
      METHODS: Patients diagnosed with abdominal wall endometriosis in their surgical
      scars from February 2008 to March 2010 were documented. The age, parity,
      symptoms, previous surgeries, initial diagnosis, diagnostic modalities,
      definitive operation, postoperative complications, histopathological evaluations
      and recurrences were recorded and analyzed. RESULTS: There were 18 patients with
      a mean age of 34.5 +/- 9.6 years. All (100%) had a gradually growing nodular
      abdominal mass in or adjacent to their cesarean incision scars. This was often
      associated with pain (83.3%), either noncyclical (26.6%) or cyclical (73.3%) in
      nature. Ultrasonography (100%), computerized tomography with intravenous contrast
      (22.2%) and/or magnetic resonance imaging (66.6%) were performed on the patients.
      All patients underwent surgery and their masses were completely excised. The mean
      diameter of the removed masses was 3.9 +/- 1.4 cm. The final pathological
      diagnosis for each case was abdominal wall endometriosis. Biannual follow-up
      examinations for two years revealed that each patient had a complete and
      uneventful recovery without recurrence. CONCLUSION: Abdominal wall endometriosis
      should be considered in the differential diagnosis of masses located at cesarean
      section incision scars, which should be excised for definitive diagnosis and
      treatment.

PMID- 22381105
TI  - Berberine-induced growth inhibition of epithelial ovarian carcinoma cell lines.
AB  - AIM: The aim of this study is to analyze the impact of berberine on the two human
      epithelial ovarian carcinoma cell lines OVCAR-3 and SKOV-3 in relation to the
      potential usefulness of berberine in the treatment of epithelial ovarian cancer.
      METHODS: Under adherent culture conditions, the cell lines were treated with
      berberine and analyzed for changes in cell growth. The cell cycle duration and
      degree of apoptosis were evaluated by means of propidium iodide staining and
      Annexin V staining. RESULTS: After the berberine treatment, the two cell lines
      showed a dose-dependent reduction in the growth rate. In the cell cycle analysis,
      the OVCAR-3 and SKOV-3 cells showed an increased DNA content of 5% in the G2/M
      phase and 7% in the S phase, respectively. Additionally, the results confirm the
      cell cycle arrest by immunoblotting and the up-regulation of p27; however, in the
      apoptosis analysis, neither cell line showed an increase in apoptosis after the
      berberine treatment. CONCLUSION: Berberine treatment can inhibit proliferation
      through a cell cycle arrest in OVCAR-3 and SKOV-3 cells. Thus, berberine may be a
      novel anticancer drug for the treatment of ovarian cancer.

PMID- 22381106
TI  - Pregnant woman with an extremely small uterus due to pelvic irradiation in
      childhood.
AB  - A female cancer survivor, having suffered malignant lymphoma during childhood and
      received radio- and chemotherapy, became pregnant. Her uterus was extremely small
      and in the 22nd week of gestation, acute uterine contractions occurred, leading
      to preterm delivery and resulting in the death of the infant. Pelvic irradiation
      in childhood was considered to have caused a small uterus and thus brought on
      preterm delivery. The younger the patient, the more vulnerable the uterus is to
      irradiation. The exposure dose to the uterus in pediatric cancer patients should
      therefore be reduced, especially in younger patients. The cooperation of
      pediatric cancer specialists and obstetricians is necessary to preserve the
      future fertility of female cancer survivors.

PMID- 22381107
TI  - Successful pregnancy in a patient suffering from recurrent mid-trimester
      miscarriage with C9 deficiency after receiving cervical cerclage followed by
      clindamycin and progesterone: a case report.
AB  - Complement component 9 (C9) deficiency is relatively common, especially in Japan.
      Here we present the case of a 27-year-old Japanese woman whose obstetric history
      involved three mid-trimester miscarriages (at 22 weeks', 18 weeks' and 21 weeks'
      gestation) and one early spontaneous miscarriage. Her fifth pregnancy was
      successfully managed by cervical cerclage at 13 weeks' gestation, followed by
      clindamycin administration (600 mg/day for 7 days) and progesterone injections
      (250 mg/week). She gave birth to a healthy 3326-g male infant at 40 weeks and 1
      day gestation after natural onset of labor. After delivery, the serum complement
      components were analyzed. C9 protein and activity were undetectable in the
      patient's serum. We suggest that an immunologic disorder such as C9 deficiency
      should be considered as a potential complication of undiagnosed recurrent
      miscarriages.

PMID- 22381108
TI  - Successful management of pregnancy-associated thrombotic thrombocytopenic purpura
      by monitoring ADAMTS13 activity.
AB  - Thrombotic thrombocytopenic purpura (TTP) during pregnancy is very rare and is
      caused by an absent or severely depleted ADAMTS13 (a disintegrin-like and
      metallopeptidase with thrombospondin type 1 motif, 13). A 37-year-old
      multigravida woman developed TTP with severe anemia and thrombocytopenia at 22
      weeks' gestation. ADAMTS13 activity was markedly decreased to 3% and ADAMTS13
      inhibitor was positive, leading to a definitive diagnosis of TTP. She was
      successfully treated by plasmapheresis six times, resulting in symptomatic
      relief. Close follow up with periodic ADAMTS13 measurement facilitated
      plasmapheresis at appropriate points at a minimum frequency during pregnancy.
      Because of intrauterine growth retardation from 28 weeks' gestation, an elective
      cesarean section was performed at 30 weeks' gestation. After delivery, the mother
      and child showed no appreciable problem. To our knowledge, this is the first
      report of successful management for pregnancy-associated TTP by monitoring
      ADAMTS13 activity during pregnancy and the postpartum period.

PMID- 22381109
TI  - Antenatally diagnosed congenital orbital teratoma in which rupture was associated
      with intrauterine fetal death.
AB  - We report a case of a fetus with a congenital orbital teratoma (COT), in which
      rupture of the tumor was associated with an intrauterine fetal demise. An
      ultrasound scan at 27 weeks' revealed a solid and cystic, complex mass in the
      orbital region with extensive vascularization suggestive of an orbital cystic
      teratoma. Magnetic resonance imaging (MRI) supported this diagnosis and clarified
      tumor localization. At 32 weeks', the patient presented with fetal demise and
      rupture of the mass was noted. Fetal COTs, like sacrococcygeal teratomas, carry
      the risk of rupture. MRI in utero is useful for evaluating the extent of disease.

PMID- 22381110
TI  - Isolated 'sign of the horns': a simple, pathognomonic, prenatal sonographic
      marker of Crisponi syndrome.
AB  - The case of a patient presenting with Crisponi syndrome recently hospitalized at
      our institution is described. During pregnancy a diagnosis of this syndrome was
      hypothesized following sonographic observation of the fetus with the hands
      showing 'the sign of the horns'. Such a finding, if isolated, as in our case, may
      represent a simple, pathognomonic sonographic marker of Crisponi syndrome.

PMID- 22381111
TI  - Primary diagnosis of metastatic breast cancer in the third trimester of
      pregnancy: a case report and review of the literature.
AB  - To the best of our knowledge, we are presenting the first documented primary
      diagnosis of a 32-year-old pregnant patient at 29 + 4 weeks' gestation with
      poorly differentiated, metastatic scirrhous breast cancer, with negative hormone
      receptors, HER-2/neu receptor overexpression and metastases in the lumbar spine.
      The patient was administered neoadjuvant chemotherapy with vinorelbine and
      trastuzumab, and received ibandronate for the bone metastases. The tumor
      responded well to treatment; however, treatment was associated with anhydramnios,
      probably related to the trastuzumab treatment. Delivery was planned for 33 + 5
      weeks' gestation by cesarean section due to concurrent breech presentation and
      anhydramnios, and the infant is in good health. After delivery, the patient
      underwent a mastectomy. Following completion of six courses of vinorelbine and
      ongoing treatment with trastuzumab and ibandronate, the patient's tumor went into
      regression and currently the patient does not present with any clinical evidence
      of disease.

PMID- 22381112
TI  - Acute renal failure induced by disseminated intravascular coagulopathy in a
      patient with adenomyosis.
AB  - Disseminated intravascular coagulation is most frequently associated with
      obstetric catastrophes, metastatic malignancy, massive trauma and bacterial
      sepsis, but relatively rarely related to benign tumors. We report on disseminated
      intravascular coagulopathy in a patient with significant adenomyosis and
      menometrorrhagia. An extremely rare case, disseminated intravascular coagulopathy
      developed in this benign case and was successfully treated with a hysterectomy
      and blood product transfusions.

PMID- 22381113
TI  - Metastatic hepatic actinomycosis masquerading as distant metastases of ovarian
      cancer.
AB  - Actinomycosis is a chronic disease characterized by abscess, tissue fibrosis and
      draining sinuses. Pelvic actinomycosis in women most commonly occurs during
      ascending infections, which are usually associated with intrauterine devices;
      however, secondary hepatic actinomycosis, while rare, can also occur. We describe
      a patient with an unusual case of metastatic hepatic actinomycosis misdiagnosed
      as distant metastases of ovarian cancer.

PMID- 22381114
TI  - Procedural pain and anxiety in paediatric patients in a Mexican emergency
      department.
AB  - AIM: This article is a report of a study carried out to investigate the
      procedures that are likely to induce pain and anxiety in children in a Mexican
      emergency department. BACKGROUND: In emergency rooms, children often experience
      unpredictable diagnostic and therapeutic procedural-related pain that can be
      associated with considerable anxiety. DESIGN: A prospective, descriptive and
      cross sectional study was conducted to investigate the prevalence of procedures
      or situations that probably induced anxiety and/or pain in children in an
      emergency room. METHODS: Procedural pain and anxiety were evaluated in children
      and adolescents (8-16 years) who were admitted to the emergency department of a
      paediatric hospital between February-September 2010. Children rated their pain
      and anxiety using a 100-mm visual analogue scale. RESULTS: A total of 252
      children with a mean age of 10.1 years were evaluated. Four-hundred fifty-nine
      procedures were completed, with an average of 1.82 events/child. Of these
      procedures, 369 (80.4%) were rated painful and 357 (77.8%) were rated stressful.
      The most frequently reported procedural pain or stressful episodes were
      peripheral catheterization, clinical examination and vascular puncture. Overall,
      32.5% of the painful events were rated severe, 32.0% were rated moderate and
      35.5% were rated slight. However, 30% of the stressful events were rated severe,
      38.9% were rated moderate and 31.1% were rated slight. Peripheral catheterization
      was rated severe in 58 children (33.9%), moderate in 55 children (32.2%) and
      slight in 58 (33.9%) children. CONCLUSION: This study provides data on common
      emergency department procedures that cause pain and anxiety in children and young
      adolescents. Healthcare providers must consider the best psychological and
      pharmacological interventions to reduce procedural anxiety and pain.

PMID- 22381115
TI  - Role of solvent-oxygen ion pairs in photooxidation of CdSe nanocrystal quantum
      dots.
AB  - Understanding the mechanisms for photodegradation of nanocrystal quantum dots is
      an important step toward their application in real-world technologies. A usual
      assumption is that photochemical modifications in nanocrystals, such as their
      photooxidation, are triggered by absorption of a photon in the dot itself. Here,
      we demonstrate that, contrary to this commonly accepted picture, nanocrystal
      oxidation can be initiated by photoexcitation of solvent-oxygen ion pairs that
      relax to produce singlet oxygen, which then reacts with the nanocrystals. We make
      this conclusion on the basis of photolysis studies of solutions of CdSe
      nanocrystals. Our measurements indicate a sharp spectral onset for
      photooxidation, which depends on solvent identity and is 4.8 eV for hexane and
      3.4 eV for toluene. Importantly, the photooxidation onset correlates with the
      position of a new optical absorption feature, which develops in a neat solvent
      upon its exposure to oxygen. This provides direct evidence that nanocrystal
      photooxidation is mediated by excitation of solvent-oxygen pairs and suggests
      that the stability of the nanocrystals is defined by not only the properties of
      their surfaces (as has been commonly believed) but also the properties of their
      environment, that is, of the surrounding solvent or matrix.

PMID- 22381116
TI  - The discovery of novel beta-secretase inhibitors: pharmacophore modeling, virtual
      screening, and docking studies.
AB  - This article describes the identification of two small molecular inhibitors for
      beta-secretase by integrating virtual screening with fluorescence resonance
      energy transfer bioassay. A ligand-based pharmacophore model was developed, and
      the sequential virtual screening of ZINC database was performed using the
      acquired pharmacophore model and molecular docking. Biological evaluation of 10
      virtual hits led to the identification of two novel inhibitors with IC(50) values
      of 4.76 and 0.31 MUm, respectively. These two moderate inhibitors could represent
      new potentials for the development of anti-Alzheimer's disease agents.

PMID- 22381117
TI  - Metabolic syndrome correlates intracoronary stenosis detected by multislice
      computed tomography in male subjects with sleep-disordered breathing.
AB  - BACKGROUND: Sleep-disordered breathing (SDB), especially obstructive sleep apnea
      (OSA), has frequent complications include hypertension, dyslipidemia and insulin
      resistance based on abdominal obesity or excess visceral fat (called Syndrome Z).
      OSA is a potential risk factor for cardiovascular diseases. The clinical
      characteristics of Japanese OSA subjects with OSA remain unclear. The present
      study investigated prevalence and predictive factors of intracoronary stenosis
      detected by multislice computed tomography (MSCT) in Japanese male subjects with
      SDB/OSA. FINDINGS: The study (O-VFStudy) subjects were 39 Japanese men with
      SDB/OSA who underwent all-night cardiorespiratory monitoring with fully attended
      polysomnography, and moreover both fat computed tomography (CT) scan and 64-row
      MSCT coronary angiography. The prevalence of coronary stenosis in this selected
      population with SDB/OSA was 15%. Logistic regression analysis showed a
      significant relationship between age-adjusted CAD and metabolic syndrome (p <
      0.05), but not serum adiponectin levels and nocturnal fall in adiponectin.
      Subjects with the metabolic syndrome had significantly higher prevalence of CAD
      (31.3 versus 4.3%, p = 0.033), and lower levels of serum adiponectin (4.5 +/- 0.6
      versus 6.4 +/- 0.6 MUg/mL, p = 0.014), compared with groups without the metabolic
      syndrome. CONCLUSIONS: The present study describes that the prevalence of greater
      than 50% intracoronary stenotic lesions detected by MSCT was 15% and the
      metabolic syndrome was correlated with intracoronary stenosis detected by MSCT in
      Japanese SDB/OSA subjects. TRIAL REGISTRATION: UMIN
      000002997https://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000003633&langu
      ge=E.

PMID- 22381119
TI  - Bartonella henselae prosthetic valve endocarditis in an adult patient with
      congenital heart disease: favorable outcome after combined medical and surgical
      management.
AB  - Bartonella spp. are a known cause of culture-negative endocarditis. We report a
      42-year-old male with underlying surgically corrected congenital heart disease
      who was diagnosed with Bartonella henselae endocarditis involving the right
      ventricle-to-pulmonary-artery conduit.

PMID- 22381121
TI  - Gender, ethnic, age, and relationship differences in non-traditional college
      student alcohol consumption: a tri-ethnic study.
AB  - Group differences in four aspects of alcohol consumption behaviors were examined
      in non-traditional college students (N = 1092; 828 women and 264 men) attending a
      large, non-residential, urban university. Findings demonstrated several
      differences between traditional and non-traditional students' drinking behaviors.
      Specifically, non-traditional students are more likely to abstain; Caucasians are
      more apt to drink in isolation and experience negative social consequences of
      drinking; Hispanic and African American women control their alcohol consumption
      better; and African American men are more likely to experience antisocial
      consequences due to drinking. These findings have implications for education and
      prevention efforts targeting non-traditional college students.

PMID- 22381120
TI  - Racial and ethnic differences in substance abuse treatment initiation and
      engagement.
AB  - This study examined variations by race and ethnicity in initiation and
      engagement, two performance measures of treatment for substance use disorders
      that focus on the timely receipt of services during the early stage of substance
      abuse treatment. Administrative data from the Oklahoma Department of Mental
      Health and Substance Abuse Services were linked with facility-level information
      from the National Survey of Substance Abuse Treatment Services. We found that
      Black clients were least likely to initiate treatment, but no race or ethnic
      differences in treatment engagement were found when compared by race or
      ethnicity. Most client and facility characteristics' association with initiation
      or engagement did not differ across racial or ethnic groups. Increased attention
      is needed to understand what may contribute to the differences and how to address
      them. This study also offers an approach that state agencies may implement for
      monitoring treatment quality and examining racial and ethnic disparities in
      substance abuse treatment services.

PMID- 22381122
TI  - Comments on "Gender, ethnic, age, and relationship differences in non-traditional
      college student alcohol consumption: a tri-ethnic study".
AB  - The purpose of these comments is to serve as a reaction to an article by
      Stephanie Babb, Cynthia Stewart, and Christine Bachman of the University of
      Houston-Downtown. The article is ambitiously titled "Gender, Ethnic, Age, and
      Relationship Differences in Non-Traditional College Students' Alcohol
      Consumption: A Tri-Ethnic Study" and is published in this issue of the Journal of
      Ethnicity in Substance Abuse. These comments are not intended to be a definitive
      response to all of the possible points raised by the authors of the article;
      rather they are reflective of the personal views of an addiction professional who
      has been active in the field for several years, particularly involved with
      efforts directed at substance use by non-traditional college students, and who
      has published previously on related topics. It is only possible to react to a few
      specific issues raised by the article; another commentator or a peer reviewer
      would probably address a myriad other areas. Indeed, several other topics of
      concern could have been addressed, but I felt it prudent and hopefully more
      productive to keep my comments more narrowly focused on some of the matters that
      seemed more pressing.

PMID- 22381123
TI  - Exploring the intersection of neighborhood racial and economic composition and
      individual race on substance use among male adolescents.
AB  - This article examines how Blacks and Whites living in neighborhoods with
      divergent racial and income profiles differed in early onset (by age 14 years)
      and adolescent lifetime prevalence (by age 18 years) of substance use, with
      longitudinal data from 473 high-risk boys (58% Black). A latent profile analysis
      identified four neighborhood classes: Black, lower-income; racially mixed, middle
      income; White, middle-income; and White, upper-income. Bivariate analyses showed
      that Blacks living in racially mixed, middle-income neighborhoods reported the
      lowest rates of tobacco and marijuana use. Whites living in White, upper-income
      neighborhoods reported higher substance use prevalence, particularly marijuana.
      Findings suggest that substance use prevention efforts are critical for Whites in
      upper-income communities.

PMID- 22381124
TI  - Latino/as in substance abuse treatment: substance use patterns, family history of
      addiction, and depression.
AB  - This study describes a sample of Latino/as in substance abuse treatment. We were
      interested in substance use patterns, gender differences, family history of
      addiction, and depression. Questionnaires completed by Latino/as (N = 209) were
      identified from 12,000 sets completed by participants in treatment from 1993
      2003. Significant gender differences emerged, with Latinas reporting higher rates
      of stimulant abuse and depression. A family history of substance use disorders in
      primary or secondary family members was reported by 91% of participants. These
      data suggest that understanding gender differences related to substance use and
      depression among Latino/as in treatment warrants attention.

PMID- 22381125
TI  - Substance use among Chinese, Filipino, and Vietnamese adult men living in San
      Jose, Daly City, and San Francisco, and its implications on ATOD prevention
      services.
AB  - This intervention study collected data on Chinese, Filipino, and Vietnamese high
      risk adults to ascertain similarities and differences in drug use patterns. Study
      participants (N = 126) participated in a 5-week intervention study to mitigate
      substance abuse and the prevalence of hepatitis C and HIV among high-risk adults
      in San Francisco, San Mateo, and Santa Clara Counties of California. Data
      reported were collected at baseline. The National Outcome Measures questionnaire
      was used to document individual substance use in the past 30 days. Filipinos
      reported higher use rates for alcohol, cigarettes, marijuana, and crack cocaine
      in the past 30 days compared with their Chinese and Vietnamese counterparts;
      these differences proved to be statistically significant (p <= .03). Data
      analysis also showed that the alcohol use of Filipino and Vietnamese homosexual
      men was significantly greater than their Chinese counterparts (p = .04). A
      statistically significant inverse association was found for alcohol use for those
      in the criminal justice system during the past 30 days (odds ratio [OR] = 0.37, p
      = .03). In addition, a positive association for other tobacco use (OR = 11.98, p
      = .00) was reported for those in the criminal justice system. Age group analyses
      indicated a positive association for those between 18-25 years old for alcohol
      use (OR = 5.40, p = .00). These data confirm the importance of disaggregation of
      data. If collapsed into a general Asian or Asian and Pacific Islander ethnic
      group category, as is often the case, the unique behaviors of the individual
      groups would be lost.

PMID- 22381126
TI  - Porphyromonas gingivalis influences actin degradation within epithelial cells
      during invasion and apoptosis.
AB  - Porphyromonas gingivalis, a Gram-negative oral pathogen, has been shown to induce
      apoptosis in human gingival epithelial cells, yet the underlining cellular
      mechanisms controlling this process are poorly understood. We have previously
      shown that the P. gingivalis proteases arginine and lysine gingipains, are
      necessary and sufficient to induce host cell apoptosis. In the present study, we
      demonstrate that 'P. gingivalis-induced apoptosis' is mediated through
      degradation of actin leading to cytoskeleton collapse. Stimulation of human
      gingival epithelial cells with P. gingivalis strains 33277 and W50 at moi:100
      induced beta-actin cleavage as early as 1 h and human serum inhibited this
      effect. By using gingipain-deficient mutants of P. gingivalis and purified
      gingipains, we demonstrate that lysine gingipain is involved in actin hydrolysis
      in a dose and time-dependent manner. Use of Jasplakinolide and cytochalasin D
      revealed that P. gingivalis internalization is necessary for actin cleavage.
      Further, we also show that lysine gingipain from P. gingivalis can cleave active
      caspase 3. Taken together, we have identified actin as a substrate for lysine
      gingipain and demonstrated a novel mechanism involved in microbial host cell
      invasion and apoptosis.

PMID- 22381127
TI  - Palladium-catalyzed decarboxylative coupling of quinolinone-3-carboxylic acids
      and related heterocyclic carboxylic acids with (hetero)aryl halides.
AB  - An efficient and practical decarboxylative cross-coupling reaction of quinolin
      4(1H)-one 3-carboxylic acids with (hetero)aryl halides has been established.
      Under a bimetallic system of PdBr(2) and silver carbonate, the protocol proved to
      be general, and a variety of 3-(hetero)aryl 4-quinolinones and related
      heterocycles, such as 3-aryl-1,8-naphthyridin-4(1H)-ones, 3-arylcoumarins, 3
      arylquinolin-2(1H)-ones, and 2-arylchromones, can be prepared in good to
      excellent yields.

PMID- 22381128
TI  - Development, validity and reliability of the Turkish version of the Hung
      Postpartum Stress Scale.
AB  - AIM: The aim of the current study was to translate the Hung Postpartum Stress
      Scale into Turkish and test the reliability and validity of the Turkish version
      of the scale. METHODS: The translation process of the Hung Postpartum Stress
      Scale into Turkish and the testing of reliability and validity of the newly
      developed scale on postpartum stress in women are described. The questionnaire
      was translated using a back-translation technique. Expert review of internal
      consistency reliability, content validity, factor analysis of construct validity
      and criterion-related validity were examined. RESULTS: Cronbach's alpha for the
      Turkish version of the Hung Postpartum Stress Scale was 0.931, indicating very
      good reliability. Factor analyses resulted in a two factor scale structure:
      maternal concerns and acceptability of the newborn by the family. Analyses also
      indicated good test-re-test reliability for the Turkish version of the Hung
      Postpartum Stress Scale (P < 0.01). CONCLUSIONS: The present study describes the
      design of a Turkish version of the Hung Postpartum Stress Scale. The newly
      developed scale proved to be reliable and valid and will be a valuable instrument
      for women's healthcare professionals.

PMID- 22381129
TI  - Hierarchical self-assembly of amphiphilic semiconducting polymers into isolated,
      bundled, and branched nanofibers.
AB  - Herein, we report a high-yield click synthesis and self-assembly of conjugated
      amphiphilic block copolymers of polythiophene (PHT) and polyethylene glycol (PEG)
      and their superstructures. A series of different length PHT(m)-b-PEG(n) with well
      defined relative block lengths was synthesized by a click-coupling reaction and
      self-assembled into uniform and stably suspended nanofibers in selective
      solvents. The length of nanofibers was controllable by varying the relative block
      lengths while keeping other dimensions and optical properties unaffected for a
      broad range of f(PHT) (0.41 to 0.82), which indicates that the packing of PHT
      dominates the self-assembly of PHT(m)-b-PEG(n). Furthermore, superstructures of
      bundled and branched nanofibers were fabricated through the self-assembly of
      PHT(m)-b-PEG(n) and preformed PHT nanofibers. The shape, length, and density of
      the hierarchical assembly structures can be controlled by varying the solvent
      quality, polymer lengths, and block copolymer/homopolymer ratio. This work
      demonstrates that complex superstructures of organic semiconductors can be
      fabricated through the bottom-up approach using preformed nanofibers as building
      blocks.

PMID- 22381130
TI  - In vitro antioxidant activity study of novel chromone derivatives.
AB  - Forty-eight chromone derivatives were evaluated for their antioxidant activity
      using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, ferrous ions
      (Fe(2+) ) chelating activity test, total antioxidant activity test (Ferric
      thiocyanate and Thiobarbituric acid methods), and total reductive capability
      (potassium ferricyanide reduction). 7,8-Dihydroxy-2-(3'-trifluoromethylphenyl)-3
      (3"-trifluoromethylbenzoyl) chromone 32 showed stronger radical scavenging and
      metal chelating activities than butylated hydroxytoluene, vitamin E, and trolox.
      Chromone derivatives that exhibited good radical scavenging and metal chelating
      also displayed strong total antioxidant and reductive power activities. The
      results obtained from this study indicated that the synthesized chromone
      derivatives have remarkable antioxidant activity.

PMID- 22381131
TI  - An ethnographic study exploring the role of ward-based Advanced Nurse
      Practitioners in an acute medical setting.
AB  - AIM: This article is a report of a study that aimed to examine the role of ward
      based Advanced Nurse Practitioners and their impact on patient care and nursing
      practice. BACKGROUND: Revised doctor/nurse skill mix combined with a focus on
      improving quality of care while reducing costs has had an impact on healthcare
      delivery in the western world. Diverse advanced nursing practice roles have
      developed and their function has varied globally over the last decade. However,
      roles and expectations for ward-based Advanced Nurse Practitioners lack clarity,
      which may hinder effective contribution to practice. DESIGN: An ethnographic
      approach was used to explore the advanced nurse practitioner role. METHODS:
      Participant observation and interviews of five ward-based Advanced Nurse
      Practitioners working in a large teaching hospital in the North West of England
      during 2009 were complemented by formal and informal interviews with staff and
      patients. Data were descriptive and broken down into themes, patterns and
      processes to enable interpretation and explanation. RESULTS: The overarching
      concept that ran through data analysis was that of Advanced Nurse Practitioners
      as a lynchpin, using their considerable expertise, networks and insider knowledge
      of health care not only to facilitate patient care but to develop a pivotal role
      facilitating nursing and medical practice. Sub-themes included enhancing
      communication and practice, acting as a role model, facilitating the patients'
      journey and pioneering the role. CONCLUSION: Ward-based Advanced Nurse
      Practitioners are pivotal and necessary for providing quality holistic patient
      care and their role can be defined as more than junior doctor substitutes.

PMID- 22381132
TI  - Close ties: an exploratory Colored Eco-Genetic Relationship Map (CEGRM) study of
      social connections of men in Familial Testicular Cancer (FTC) families.
AB  - BACKGROUND: Testicular cancer, while rare compared with other adult solid tumors,
      is the most common cancer in young men in northern Europe and North America. Risk
      factors include white race, positive family history, contralateral testicular
      cancer, cryptorchidism, infertility and testicular microlithiasis. As the genetic
      causes of familial clusters (Familial Testicular Cancer or FTC) are being sought,
      it is also important to understand the psycho-social experiences of members of
      FTC families. METHODS: This is a cross-sectional examination via the Colored Eco
      Genetic Relationship Map (CEGRM) of social connections reported by 49 men in FTC
      families participating in NCI research study 02-C-178. RESULTS: The CEGRM was
      acceptable and feasible for use with men in FTC families, and valuable in
      understanding their social connections. These men have largely adjusted to the TC
      history in themselves and/or their relatives. They have considerable social and
      emotional support from family and friends, although there is wide variability in
      sources and types. CONCLUSIONS: The CEGRM focuses on men's social connections and
      close emotional bonds in FTC families. This action-oriented process of placing
      colored symbols on significant relationships uncovered previously under
      appreciated emotions accompanying men's social exchanges. Most men in FTC
      families succeed in re-establishing a sense of normalcy in their lives and social
      connections, in the aftermath of a testicular cancer diagnosis.

PMID- 22381134
TI  - Nexilin is a dynamic component of Listeria monocytogenes and enteropathogenic
      Escherichia coli actin-rich structures.
AB  - The bacterial pathogens Listeria monocytogenes and enteropathogenic Escherichia
      coli (EPEC) generate motile actin-rich structures (comet tails and pedestals) as
      part of their infectious processes. Nexilin, an actin-associated protein and a
      component of focal adhesions, has been suggested to be involved in actin-based
      motility. To determine whether nexilin is commandeered during L. monocytogenes
      and EPEC infections, we infected cultured cells and found that nexilin is crucial
      for L. monocytogenes invasion as levels of internalized bacteria were
      significantly decreased in nexilin-targeted siRNA-treated cells. In addition,
      nexilin is a component of the machinery that drives the formation of L.
      monocytogenes comet tails and EPEC pedestals. Nexilin colocalizes with stationary
      bacteria and accumulates at the distal portion of comet tails and pedestals of
      motile bacteria. We also show that nexilin is crucial for efficient comet tail
      formation as cells pre-treated with nexilin siRNA generate malformed comet tails,
      whereas nexilin is dispensable during EPEC pedestal generation. These findings
      demonstrate that nexilin is required for efficient infection with invasive and
      adherent bacteria and is key to the actin-rich structures these microbes
      generate.

PMID- 22381133
TI  - Epidemiology of infections in children with acquired aplastic anaemia: a
      retrospective multicenter study in Italy.
AB  - Infection is a significant cause of death in patients with aplastic anaemia (AA).
      However, few studies have examined the characteristics of infections in patients
      with AA, especially in children. The aim of this retrospective study was to
      evaluate the incidence and types of infections in a large cohort of paediatric
      patients with AA referred to eight AIEOP (Italian Association of Paediatric
      Oncology and Haematology) centres in Italy. The study included 78 patients, 45
      boys and 33 girls, median age 9.29 yrs (1st-3rd quartile 3.59-13.09) diagnosed
      with AA. During the study period, 111 infectious episodes were observed in 42
      (54%) patients. Fifty-one (46%) episodes were fever of unknown origin and 60
      (54%) were documented infections (DI). In this group, microbiologically
      documented infection (MDI) with bacteremia accounted for 23 (38%) episodes, MDI
      without bacteremia for 7 (12%), clinically documented infection for 25 (42%) and
      invasive fungal diseases for 5 (8%). The rate (episodes/1000 d at risk) was
      similar in severe aplastic anemia and very severe aplastic anemia both before and
      after day 120. During the first 120 d from diagnosis, the cumulative risk of a DI
      was 21% (95% CI 12-29) with the last episode at day 117, but the 50% of episodes
      were observed in the first 24 d. After day 120, the cumulative risk of DI was
      again 21% (95% CI 12-29), with the last episode at day 445 of follow-up, with 50%
      of episodes observed in the first 120 d of observation (240 d from the diagnosis
      of AA). We found a statistically significant association between the grade of
      aplasia at diagnosis and the incidence of IEs (P = 0.0002). No association was
      found between gender, age at diagnosis, response at day +120 and at day +180, use
      of G-CSF and occurrence of IEs. The actuarial overall survival at 5 yrs was 90%
      +/- 3.6. The mortality rate attributable to infection complication was 9%. This
      is a large paediatric cohort study reporting the epidemiology of infectious
      complications in children with AA and that allow us to compare the
      epidemiological data in this diseases with that of the most recent studies in
      neutropenic children with cancer. Our findings confirm that infections represent
      the main cause of death in patients with AA and they are important for the design
      of management strategies of febrile neutropenia in these patients.

PMID- 22381135
TI  - Effects of Ginkgo biloba extracts on pharmacokinetics and efficacy of
      atorvastatin based on plasma indices.
AB  - Ginkgo biloba extract (GBE) is one of the most widely used herbal medicines in
      the world. It is often administered in combination with statins to treat
      diseases, especially some nervous system disorders. We aimed to investigate the
      influences of GBE on pharmacokinetics and efficacy of atorvastatin, which are
      currently unclear. Sixteen volunteers received a single oral dose of 40 mg
      atorvastatin, followed by a wash-out period of at least 5 days. Then the
      volunteers took 360 mg GBE daily for 14 days, followed by a single dose of 40 mg
      atorvastatin. Serial blood samples obtained over a period of 48 h after
      atorvastatin ingestion were subjected to determination of atorvastatin plasma
      concentrations and markers of cholesterol synthesis (lathosterol) and cholesterol
      absorption (sitosterol). With GBE administration, AUC0-48, AUC(0-infinity) and
      C(max) of atorvastatin were reduced by 14.27% (p = 0.005), 10.00% (p = 0.03) and
      28.93% (p = 0.002), respectively; Vd/F and CL/F of atorvastatin were increased by
      31.95% (p = 0.017) and 6.48% (p = 0.044). After 14 days of treatment, GBE has no
      significant effects on cholesterol-lowering efficacy of atorvastatin. This study
      suggests that GBE slightly decreases the plasma atorvastatin concentrations, but
      has no meaningful effect on the cholesterol-lowering efficacy of atorvastatin.

PMID- 22381136
TI  - Large Stokes shift fluorescent dyes based on a highly substituted terephthalic
      acid core.
AB  - The synthesis of dyes based on a highly substituted terephthalic acid core is
      described, starting from readily available 2,5-dihydroxy-terephthalic acid
      diethyl ester. The dyes are highly colored, soluble in organic solvents and
      reasonably fluorescent in solution and in the solid state. The maxima for
      absorption and emission are around 402 and 502 nm, respectively. The fluorophores
      are readily cyclized to generate compounds which comprise the basic 6,13
      dihydroxy-chromeno[2,3-b]xanthene-7,14-dione unit. These new derivatives are
      nonfluorescent.

PMID- 22381137
TI  - Effectiveness of a diet and physical activity promotion strategy on the
      prevention of obesity in Mexican school children.
AB  - BACKGROUND: Overweight and obesity in children in Mexico was among the countries
      with the highest prevalence's in the world. Mexico currently has few innovative
      and comprehensive experiences to help curb the growth of this serious public
      health problem. Therefore, the aim of this study is to assess the effectiveness
      of a nutrition and physical activity strategy, called "Nutrition on the Go"
      ("nutricion en movimiento") in maintaining the BMI values of school children in
      the State of Mexico. METHODS: A two-stage cluster trial was carried out. Sixty
      schools were selected in the State of Mexico, of which 30 were randomly assigned
      to the intervention group (IG) and 30 to the control group (CG). A total of 1020
      fifth grade school children participated. The intervention strategy aimed to
      decrease the energy content of school breakfasts and include fruits and
      vegetables, as well as increase physical activity and the consumption of water
      during the time spent at school. The strategy was implemented over a 6-month
      period. RESULTS: The estimated probability (EP) of obesity between baseline and
      the final stage for the IG decreased 1% (Initial EP = 11.8%, 95%CI 9.0, 15.2,
      final EP = 10.8, 95%CI 8.4, 13.) For the CG, the probability increased 0.9%
      (baseline EP = 10.6%; 95%CI 8.1, 13.7; final EP = 11.5, 95%CI 9.0, 14.6). The
      interaction between the intervention and the stage is the average odd time
      corrected treatment effect, which is statistically significant (p = 0.01) (OR =
      0.68, 95%CI 0.52, 091).This represents the interaction between intervention and
      stage, which is highly significant (p = 0.01) (OR = 0.68; 95%CI 0.52, 091). In
      addition, girls had a protective effect on obesity (OR = 0.56; 95%CI 0.39, 0.80).
      CONCLUSIONS: The intervention strategy is effective in maintaining the BMI of
      school children.

PMID- 22381138
TI  - Histology-specific long-term trends in the incidence of ovarian cancer and
      borderline tumor in Japanese females: a population-based study from 1983 to 2007
      in Niigata.
AB  - AIM: The histology-specific long-term trends in the incidence of ovarian cancer
      and borderline tumors in Japanese women were examined, based on data from the
      population-based cancer registry in Niigata, Japan. MATERIAL AND METHODS: Data
      were obtained from the Niigata Gynecological Cancer Registry, which covered the
      entire female population in Niigata prefecture, Japan, during the period from
      1983 to 2007. RESULTS: A total of 3134 females with epithelial ovarian cancer,
      including borderline tumor cases, were diagnosed between 1983 and 2007. The age
      standardized rates (ASRs) of both ovarian cancer and borderline tumors have
      steadily increased, with significant changes in ovarian cancer in all age groups,
      and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid
      adenocarcinoma showed a steady increasing trend, and those of clear cell and
      mucinous adenocarcinomas showed significant increasing trends in the total
      population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in
      the 50+ age group were significantly increased, especially the incidence of clear
      cell adenocarcinoma, which strikingly increased by approximately threefold from
      1.2 (1983-1989) to 3.5 (2000-2007) per 100,000 females. CONCLUSION: This
      prefecture-wide study showed the practical trends in ovarian cancer and
      borderline tumors in Japanese females. The incidence of ovarian cancer has
      steadily increased, with significant increases in the incidence of clear cell and
      mucinous adenocarcinomas in the total population during the past two decades.
      Because of the poor response rate of these histological subtypes to platinum
      based regimens, novel treatment approaches should be adopted to improve the
      prognostic outcome in patients with ovarian cancer in Japan.

PMID- 22381139
TI  - Regulation of the human prostacyclin receptor gene in megakaryocytes: major roles
      for C/EBPdelta and PU.1.
AB  - The prostanoid prostacyclin plays a central role in haemostasis and vascular
      repair. Recent studies investigating the regulation of the human prostacyclin
      receptor (hIP) gene identified an upstream repressor region (URR) within its
      regulatory promoter, herein termed the PrmIP. This study aimed to identify the
      main trans-acting factors that bind within the URR to transcriptionally repress
      PrmIP-directed gene expression in the megakaryoblastic human erythroleukemia
      (HEL) 92.1.7 cell line. Of the putative cis-acting elements examined, disruption
      of C/EBP and PU.1 elements within the URR substantially increased PrmIP-directed
      gene expression. Chromatin immunoprecipitation (ChIP) confirmed that C/EBPdelta
      and PU.1, but not C/EBPbeta, bind to the URR in vivo, while ectopic expression of
      C/EBPdelta substantially reduced hIP mRNA levels and PrmIP-directed gene
      expression. Phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic
      differentiation increased hIP mRNA and PrmIP-directed reporter gene expression
      and hIP-mediated cAMP generation in HEL cells. Two PMA-responsive regions, termed
      PRR1 and PRR2, were identified within PrmIP. Disruption of C/EBPdelta and PU.1
      cis-elements within the overlapping PRR1/URR and of Sp1, PU.1 and Oct-1 cis
      elements within the overlapping PRR2/core PrmIP, revealed that both PRR1 and PRR2
      contribute to the PMA- induction of hIP mRNA and gene expression in HEL cells.
      Furthermore, ChIP analysis established that induction of PrmIP-directed gene
      expression during megakaryocytic differentiation is largely regulated by PMA
      induced dissociation of C/EBPdelta and enhanced binding of PU.1 to PRR1 in
      addition to increased binding of Sp1, PU.1 and Oct-1 to elements within the core
      promoter/PRR2 in vivo. Taken together, these data provide critical insights into
      the transcriptional regulation of the hIP gene within the vasculature, including
      during megakaryocytic differentiation.

PMID- 22381140
TI  - The ghosts in the machine: DNA methylation and the mystery of differentiation.
AB  - Methylation regulates DNA by altering chromatin and limiting accessibility of
      transcription factors and RNA polymerase. In this way, DNA methylation controls
      gene expression and plays a role in ES cell regulation, tissue differentiation
      and the development of the organism. In abnormal circumstances methylation can
      also induce diseases and promote cancer progression. Chromatin remodeling
      proteins such as the SNF2 family member Lsh regulates genome-wide cytosine
      methylation patterns during mammalian development. Lsh promotes methylation by
      targeting and repressing repeat sequences that are imbedded in heterochromatin.
      Lsh also regulates cytosine methylation at unique loci. Alterations in histone
      modifications (such as H3K4me3, histone acetylation, H3K27me3 and H2Aub) can be
      associated with DNA methylation changes making Lsh-mediated cytosine methylation
      part of a larger epigenetic network defining gene expression and cellular
      differentiation during development. This article is part of a Special Issue
      entitled: Chromatin in time and space.

PMID- 22381141
TI  - Caller characteristics, call contents, and types of assistance provided by caller
      sex and age group in a Canadian Inuit crisis line in Nunavut, 1991-2001.
AB  - Analysis of calls made to a northern Canadian Inuit crisis line in the territory
      of Nunavut between 1991 and 2001 revealed that the majority of users were adult
      females who called to discuss problems primarily related to relationships and
      loneliness/boredom. Younger callers tended to make prank calls. The volunteer
      staff used mostly empathetic listening and suggestions. Referral recommendations
      made were primarily to social services. Although some callers experienced a
      language barrier, others found the service to be helpful. Results suggest that
      the crisis line was underused by young Inuit males who represent a group that are
      most in need of crisis intervention.

PMID- 22381142
TI  - Diversity oriented one-pot three-component sequential synthesis of annulated
      benzothiazoloquinazolines.
AB  - Annulated benzothiazoloquinazolines have been synthesized by a diversity
      oriented simple and convenient synthesis involving one-pot three-component
      reaction of substituted 2-aminobenzothiazoles with alpha-tetralone and
      aromatic/heteroaromatic aldehydes in ethanol in the presence of catalytic amount
      of triethylamine. The synthesized compounds have been characterized by their
      elemental analyses and spectral data.

PMID- 22381143
TI  - Rhodium-catalyzed carbonylation of 3-acyloxy-1,4-enynes for the synthesis of
      cyclopentenones.
AB  - Functionalized cyclopentenones were synthesized by a Rh-catalyzed carbonylation
      of 3-acyloxy-1,4-enynes, derived from alkynes and alpha,beta-unsaturated
      aldehydes. The reaction involved a Saucy-Marbet 1,3-acyloxy migration of
      propargyl esters and a [4 + 1] cycloaddition of the resulting acyloxy substituted
      vinylallene with CO.

PMID- 22381146
TI  - Current state of medical-advice-seeking behaviour for symptoms of colorectal
      cancer: determinants of failure and delay in medical consultation.
AB  - AIM: There are few data on the factors associated with healthcare-seeking
      behaviour for symptoms of colorectal cancer. This study describes the
      determinants of failure and delay in seeking medical advice for rectal bleeding
      and change in bowel habit. METHOD: In total, 1592 persons (56-88 years) were
      randomly selected from the Hunter Community Study and mailed a questionnaire.
      RESULTS: In all, 18% (60/332) of respondents experiencing rectal bleeding and 20%
      (39/195) reporting change in bowel habit had never consulted a doctor. The rate
      of delay (>1 month) for each symptom was 18% and 37%. The reasons for delay
      included the assumption that the symptoms were not serious or that they were
      benign. Triggers for seeking medical advice varied. Healthcare-seeking behaviour
      for rectal bleeding had not significantly improved compared with a previous
      community-based study. CONCLUSION: The seriousness of symptoms, importance of
      early detection and prompt medical consultation must be articulated in health
      messages to at-risk persons.

PMID- 22381145
TI  - Ginsenoside Rg1 attenuates oligomeric Abeta(1-42)-induced mitochondrial
      dysfunction.
AB  - Mitochondrial dysfunction is one of the major pathological changes seen in
      Alzheimer's disease (AD). Amyloid beta-peptide (Abeta), a neurotoxic peptide,
      accumulates in the brain of AD subjects and mediates mitochondrial and neuronal
      stress. Therefore, protecting mitochondrion from Abeta-induced toxicity holds
      potential benefits for halting and treating and perhaps preventing AD. Here, we
      report that administration of ginsenoside Rg1, a known neuroprotective drug, to
      primary cultured cortical neurons, rescues Abeta-mediated mitochondrial
      dysfunction as shown by increases in mitochondrial membrane potential, ATP
      levels, activity of cytochrome c oxidase (a key enzyme associated with
      mitochondrial respiratory function), and decreases in cytochrome c release. The
      protective effects of Rg1 on mitochondrial dysfunction correlate to neuronal
      injury in the presence of Abeta. This finding suggests that ginsenoside Rg1 may
      attenuate Abeta-induced neuronal death through the suppression of intracellular
      mitochondrial oxidative stress and may rescue neurons in AD.

PMID- 22381147
TI  - Low iodine intake during pregnancy: relationship to placental development and
      head circumference in newborn.
AB  - INTRODUCTION: Iodine is considered to be an essential micronutrient in pregnant
      women. Iodine placental transport to the embryo-fetus is essential for hormone
      synthesis and is crucial for nervous system development. However, the
      relationship between iodine intake and placental weight and its potential
      implications for the newborn have not been studied. MATERIAL AND METHODS: Iodine
      intake was analyzed in 77 pregnant women based on urinary iodine excretion (UIE)
      levels, measured using Pinos modified method (normal value, >= 150 MUg/L).
      Placental weight was measured (PW: normal, >=500 g). In the newborn, weight,
      height, and head perimeter (HP) were also measured. Placental index (PI:
      placental weight/newborn weight) was calculated, and was considered normal if
      >=0.15. RESULTS: UIE was normal in 50 pregnant women (mean +/- SD, 279 MUg/L +/-
      70.22 MUg/L) and decreased in 27 (94 MUg/L +/- 31.49 MUg/L). Newborns of mothers
      with low UIE had a similar weight (3357 g +/- 416.30 g; n: 27) to those of
      mothers with normal UIE (3489 g +/- 560.59 g; n: 50). Forty-four percent of
      mothers with low UIE had PW <500 g, and statistically lower HPs were found in
      newborns of mothers with low PW (PW(3)500 g: 36.05 cm +/- 0.55 cm, n: 54; PW <500
      g: 33.93 cm +/- 15 cm, n:23, p<0.019). Similar results were found with PI, but
      they did not reach statistical significance (0,17 +/- 0,04; p=0.066). No
      differences were seen in all other parameters. CONCLUSION: The study suggests the
      existence of a relationship between PW and HP. This finding may be related to
      iodine intake during pregnancy.

PMID- 22381148
TI  - Mining label data: assessing the presence of ortho-phthalates in pharmaceuticals
      and dietary supplements.

PMID- 22381149
TI  - Impact of genital warts on health related quality of life in men and women in
      mainland China: a multicenter hospital-based cross-sectional study.
AB  - BACKGROUND: Information on the health-related quality of life (HRQoL) of patients
      with genital warts (GW) in populations in mainland China is still limited. The
      aim of the study was to use a generic instrument to measure the impact of genital
      warts on HRQoL in men and women in this setting. METHODS: A multi-centre hospital
      based cross-sectional study across 18 centers in China was conducted to interview
      patients using the European quality of life-5 dimension (EQ-5D) instrument;
      respondents' demographic and clinical data were also collected. RESULTS: A total
      of 1,358 GW patients (612 men, 746 women) were included in the analysis, with a
      mean age of 32.0 +/- 10.6 years. 56.4% of the patients reported some problems in
      the dimension of Anxiety/Depression (highest), followed by Pain/Discomfort
      (24.7%) and Mobility (3.5%). The overall visual analogue scale (VAS) score of the
      study population was found to be 65.2 +/- 22.0, and the EQ-5D index score was
      found to be 0.843 +/- 0.129 using Japanese preference weights (the Chinese
      preference was unavailable yet). Patients with lower VAS means and EQ-5D index
      scores were more often female, living in urban area, and suffering multiple GW
      (all p values < 0.05), but the values did not differ notably by age (p values >
      0.05). CONCLUSIONS: The HRQoL of patients with GW was substantially lower,
      compared to a national representative general population in China (VAS = ~80);
      the findings of different subgroups are informative for future GW prevention and
      control efforts.

PMID- 22381150
TI  - Spontaneous reports of primarily suspected herbal hepatotoxicity by Pelargonium
      sidoides: was causality adequately ascertained?
AB  - Spontaneous reports of primarily assumed hepatotoxicity in connection with the
      use of Pelargonium sidoides (PS) have been interpreted by the Drug Commission of
      the German Medical Association (DCGMA) as showing some hepatotoxic potential of
      PS used to treat common cold and other respiratory tract infections. Causality
      for PS was assessed using the liver specific, structured, quantitative, and
      updated scale of the Council for International Organizations of Medical Sciences
      (CIOMS). In none of the 15 cases was there a highly probable or probable
      causality for PS. Analysis revealed confounding factors such as numerous final
      diagnoses unrelated to PS and poor data quality in virtually all cases. In only a
      minority of the cases were data provided to consider even common other diseases
      of the liver. For instance, biliary tract imaging data were available in only 3
      patients; data to exclude virus infections by hepatitis A-C were provided in 4
      cases and by CMV and EBV in 1 case, whereas HSV and VZV virus infections remained
      unconsidered. Thus, convincing evidence is lacking that PS was a potential
      hepatotoxin in the analyzed cases.

PMID- 22381151
TI  - What factors may influence psychological well being at three months and one year
      post BRCA genetic result disclosure?
AB  - Genetic testing for breast cancer predisposition has been available in the
      clinical practice for more than a decade. How the result of genetic testing
      affects the psychological well-being of the individuals is an under-researched
      area in many populations. Follow-up analysis of psychological well-being via HADS
      scale was performed in 364 individuals at 3 months and 1 year after the
      disclosure of BRCA1/2 genetic result. We analyzed potential predictors for
      pathological anxiety and variables associated to the variation of HADS scores
      over time. At pre-test only 16% and 4% of individuals presented symptoms of
      anxiety and depression, respectively. Having a prior diagnosis of cancer and
      presenting a pathological HADS-A score at the baseline were associated with
      clinically significant anxiety scores at one year, but the genetic test result
      was not. Thus, BRCA genetic testing does not influence short and long term
      anxiety and depression levels among those identified as mutation carriers. It is
      our task to demystify the allegedly negative impact of BRCA testing on
      psychological well being to increase the uptake of genetic testing and benefit
      those who are at high risk of developing breast, ovarian and prostate cancer.

PMID- 22381152
TI  - Alcohol and breast cancer.

PMID- 22381153
TI  - Socio-demographic factors and reasons associated with delay in breast cancer
      presentation: a study in Nigerian women.
AB  - We evaluated the effects of selected socio-demographic factors on late
      presentation and reasons why our breast cancer patients delay reporting for
      treatment. All female breast cancer patients referred to one of the general
      surgery out-patient clinics of Lagos State University Teaching Hospital between
      January 2009 and December 2010 were interviewed. Relevant socio-demographic and
      clinical data were obtained and reasons for patient delay documented. Univariate
      and multivariate logistic regression analyses were conducted to calculate odd
      ratio for delay. A total of 201 patients were enrolled. Mean duration of symptoms
      was 12.12 months (SD +/- 5.18). Delay for more than 3 months before initial
      medical consultation was observed in 164 patients (81.6%). Increased risk of late
      presentation was associated with single women (OR=2.054), primary level of
      education (OR=3.059), negative history of benign breast disease (OR=1.648) and
      pre-menopause (OR=1.861). Ignorance of the nature of illness, belief in spiritual
      healing, fear of mastectomy and belief in herbal treatment were the leading
      reasons for delay. Women with higher risk of late presentation should be the
      target group during interventions aimed at raising breast cancer awareness.
      Reasons for patient delay should also be addressed.

PMID- 22381154
TI  - Putative relationship between hormonal status and serum pyrrolidone
      carboxypeptidase activity in pre- and post- menopausal women with breast cancer.
AB  - In breast cancer, hormonal changes are rather constant in post-menopausal women
      since they tend to vary only over long time spans. However, in pre-menopausal
      women, the development of breast cancer is associated with hormonal physiological
      variations. The aim of the present work was to analyse the changes in circulating
      levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone
      (FSH) and luteinizing hormone (LH) in pre- and post-menopausal women that were
      healthy or with breast cancer, and their connection to serum pyrrolidone
      carboxypeptidase (Pcp) activity. We observed significant changes in the hormonal
      profile in post-menopausal women with breast cancer compared to the control
      group. In pre-menopausal women, we found significant changes in circulating GnRH
      levels with respect to the healthy group. Our present results support the
      existence of neuroendocrine misregulation that could be involved in tumour
      progression, with Pcp being a potentially new pharmacological target in breast
      cancer treatments.

PMID- 22381155
TI  - Temporal patterns of lipid testing and statin therapy in acute coronary syndrome
      patients (from the Canadian GRACE Experience).
AB  - Current guidelines recommend the measurement of fasting lipid profile and use of
      statins in all patients with acute coronary syndrome (ACS). However, the temporal
      trends of lipid testing and statin therapy in "real-world" patients with ACS are
      unclear. From January 1999 through December 2008, the prospective, multicenter,
      Global Registry of Acute Coronary Events (GRACE/GRACE(2)/CANRACE) enrolled 13,947
      patients with ACS in Canada. We stratified the study population based on year of
      presentation into 3 groups (1999 to 2004, 2005 to 2006, and 2007 to 2008) and
      compared the use of lipid testing and use of statin therapy in hospital. Overall,
      70.8% of patients underwent lipid testing and 79.4% received in-hospital statin
      therapy; these patients were younger and had lower GRACE risk scores (p <0.001
      for the 2 comparisons) compared to those who did not. Over time there was a
      significant increase in rates of in-hospital statin therapy (70% in 1999 to 2004
      to 84.5% in 2007 to 2008, p for trend < 0.001) but only a minor increase in rates
      of lipid testing (69.4% in 1999 to 2004 to 72.4% in 2007 to 2008, p for trend =
      0.003). After adjusting for confounders, this increasing temporal trend remained
      statistically significant for statin therapy (p <0.001) but not for lipid
      testing. Lipid testing was independently associated with in-hospital statin use
      (adjusted odds ratio 1.62, 95% confidence interval 1.27 to 2.08, p <0.001). In
      patients who did have lipid testing, those with low-density lipoprotein
      cholesterol level >130 mg/dl (3.4 mmol/L) were more likely to be treated with in
      hospital statins. In conclusion, there has been a significant temporal increase
      in the use of in-hospital statin therapy but only a minor increase in lipid
      testing. Lipid testing was strongly associated with in-hospital statin use. A
      substantial proportion of patients with ACS, especially those at higher risk,
      still do not receive these guideline-recommended interventions in contemporary
      practice.

PMID- 22381156
TI  - Virtual histology-intravascular ultrasound assessment of lesion coverage after
      angiographically-guided stent implantation in patients with ST Elevation
      myocardial infarction undergoing primary percutaneous coronary intervention.
AB  - An occlusion or severe stenosis (angiographic culprit lesion) of the infarct
      related artery is frequently located at the site of the maximum thrombus burden,
      whereas the origin of the plaque rupture (the true culprit) can be situated
      proximal or distal to it. The aim of this study was to examine stent coverage of
      true culprit lesions in 20 patients who underwent primary percutaneous coronary
      intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow
      restored in the infarct-related artery by angiographically guided direct
      stenting. Images of lesions were obtained using virtual histology-intravascular
      ultrasound before and after intervention (blinded to the operator). Plaque
      rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11
      proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core
      sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and
      distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents
      in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap
      fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the
      proximal reference segment and in 3 patients in the proximal and distal reference
      segments. In conclusion, in about 50% of patients who undergo primary
      percutaneous coronary intervention for ST-segment elevation myocardial infarction
      with optimal angiographic results, the stent does not fully cover the maximum
      necrotic core site related to the culprit lesion.

PMID- 22381157
TI  - N-terminal pro-brain natriuretic peptide and angiotensin-converting enzyme-2
      levels and their association with postoperative cardiac complications after
      emergency orthopedic surgery.
AB  - The prognostic usefulness of the cardiac biomarkers N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and angiotensin-converting enzyme 2 (ACE-2), in
      predicting adverse cardiac outcomes after orthopedic surgery is not well studied.
      The aim of our study was to determine the usefulness of perioperative NT-proBNP
      and ACE-2 for predicting cardiac events after emergency orthopedic surgery. The
      perioperative NT-proBNP and ACE-2 levels were determined in 187 consecutive
      patients aged >60 years who underwent orthopedic surgery with 1 year of follow-up
      for any cardiac complications (defined as acute myocardial infarction, congestive
      cardiac failure, atrial fibrillation, or major arrhythmia) and death. Of the 187
      patients, 20 (10.7%) sustained an in-hospital postoperative cardiac complication.
      The total all-cause in-hospital and 1-year mortality rate was 1.6% (3 of 187) and
      8.6% (16 of 187), respectively. The median preoperative and postoperative NT
      proBNP level was greater in patients who sustained an in-hospital cardiac event
      than in those who had not (386 vs 2,273 pg/ml, p <0.001, and 605 vs 4,316 pg/ml,
      p <0.001, respectively). Similarly, the postoperative median ACE-2 levels were
      significantly greater in the patients with an in-hospital cardiac event than in
      those without (25.3 vs 39.5 pmol/ml/min, p = 0.012). A preoperative NT-proBNP
      level of >=741 pg/ml (odds ratio 4.5, 95% confidence interval 1.3 to 15.2, p =
      0.017), postoperative troponin elevation (odds ratio 4.9, 95% confidence interval
      1.3 to 18.9, p = 0.022), and number of co-morbidities (odds ratio 1.8, 95%
      confidence interval 1.2 to 2.8, p = 0.009) independently predicted in-hospital
      cardiac complications on multivariate analysis. The pre- and postoperative NT
      proBNP level independently predicted 1-year cardiovascular complications but not
      the ACE-2 levels. In conclusion, elevated perioperative NT-proBNP predicted in
      hospital and 1-year cardiac events in an emergency orthopedic population but the
      ACE-2 levels did not, which requires additional study for validation.

PMID- 22381158
TI  - Hypertrophic cardiomyopathy with longevity to 90 years or older.
AB  - Hypertrophic cardiomyopathy (HC) is the most common cause of sudden death in the
      young, but survival to particularly advanced age is less well appreciated. The
      investigators report the prevalence, clinical features, and demographics of
      patients with HC surviving to >=90 years of age. Of 1,297 patients with HC in the
      Hypertrophic Cardiomyopathy Center database (Minneapolis Heart Institute
      Foundation), 26 (2.0%) were identified who had achieved the age of >=90 years; 18
      (69%) were women. HC diagnosis came late in life, at 61 to 92 years (mean 80 +/-
      8; >=75 years in 21 patients), recognized fortuitously by the detection of a
      heart murmur or during family screening (n = 6) or after onset of new symptoms (n
      = 20). At most recent evaluation (or death) patients were aged 90 to 96.7 years
      (mean 92.2 +/- 2), with 6 presently alive at 91 to 96 years of age; HC did not
      appear to be the primary cause of death in any patient. Left ventricular wall
      thicknesses were 15 to 31 mm (mean 20 +/- 3); 8 patients (31%) had obstruction to
      left ventricular outflow at rest (peak instantaneous gradients, 38 to 135 mm Hg).
      Significant HC-related complications occurred in 13 patients (50%), including
      progressive heart failure symptoms, atrial fibrillation, and nonfatal embolic
      stroke. Although no patient died suddenly, 13 (50%) nevertheless carried
      conventional HC risk markers. A greater proportion of cohort patients reached
      >=90 years of age (2.0%) than expected in the general population (0.8%) (p
      <0.001). In conclusion, HC may be unrecognized until late in life and is
      consistent with survival to particularly advanced age into the 10th decade of
      life without the need for major HC-related treatment interventions, and with
      demise ultimately largely unrelated to this disease. This principle regarding the
      natural history of HC can afford a measure of reassurance to many patients.

PMID- 22381159
TI  - How the 2008 stock market crash and seasons affect total and cardiac deaths in
      Los Angeles County.
AB  - Various stressors trigger cardiac death. The objective was to investigate a
      possible relation between a stock market crash and cardiac death in a large
      population within the United States. We obtained daily stock market data (Dow
      Jones Industrial Average Index), death certificate data for daily deaths in Los
      Angeles County (LA), and annual LA population estimates for 2005 through 2008.
      The 4 years death rate curves (2005 through 2008) were averaged into a single
      curve to illustrate annual trends. Data were "deseasonalized" by subtracting from
      the daily observed value the average value for that day of year. There was marked
      seasonal variation in total and cardiac death rates. Even in the mild LA climate,
      death rates were higher in winter versus summer including total death (+17%),
      circulatory death (+24%), coronary heart disease death (+28%), and myocardial
      infarction death (+38%) rates (p <0.0001 for each). Absolute coronary heart
      disease death rates have decreased since 1985. After accounting for seasonal
      variation, the large stock market crash in October 2008 did not affect death
      rates in LA. Death rates remained at or below seasonal averages during the stock
      market crash. In conclusion, after correcting for seasonal variation, the stock
      market crash in October 2008 was not associated with an increase in total or
      cardiac death in LA. Annual coronary heart disease death rates continue to
      decrease. However, seasonal variation (specifically winter) remains a trigger for
      death and coronary heart disease death even in LA where winters are mild.

PMID- 22381161
TI  - Usefulness of the left ventricular myocardial contraction fraction in healthy men
      and women to predict cardiovascular morbidity and mortality.
AB  - We sought to determine whether depressed myocardial contraction fraction (MCF;
      ratio of left ventricular [LV] stroke volume to myocardial volume) predicts
      cardiovascular disease (CVD) events in initially healthy adults. A subset (n =
      318, 60 +/- 9 years old, 158 men) of the Framingham Heart Study Offspring cohort
      free of clinical CVD underwent volumetric cardiovascular magnetic resonance
      imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were
      determined. "Hard" CVD events consisted of cardiovascular death, myocardial
      infarction, stroke, or new heart failure. A Cox proportional hazards model
      adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios
      for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and
      LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served
      as referents. Kaplan-Meier survival plots and log-rank test were used to compare
      event-free survival. MCF was greater in women (0.58 +/- 0.13) than in men (0.52
      +/- 0.11, p <0.01). Nearly all participants (99%) had EF >=0.55. During an up to
      9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard
      CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD
      (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased
      hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p =
      0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk
      (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest
      quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a
      cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an
      increased hazard for hard CVD events after adjustment for traditional CVD risk
      factors and LV mass.

PMID- 22381162
TI  - Meta-analysis of randomized controlled trials on effect of cilostazol on
      restenosis rates and outcomes after percutaneous coronary intervention.
AB  - Cilostazol is a generic drug with antiplatelet and antiproliferative effects. It
      is unclear whether adding cilostazol to standard dual antiplatelet therapy
      (aspirin and clopidogrel) after percutaneous coronary intervention reduces
      restenosis and improves the outcomes. We, therefore, conducted a systematic
      review and meta-analysis. We systematically searched the Cochrane Library,
      EMBASE, and MEDLINE databases for randomized controlled trials comparing dual
      antiplatelet therapy with and without cilostazol after percutaneous coronary
      intervention. The data were pooled using random-effects models and stratified
      into short-term (1-month), midterm (1- to 12-month), and long-term (>=12-month)
      follow-up durations. Twelve randomized controlled trials involving 5,655 patients
      met our inclusion criteria. The addition of cilostazol to dual antiplatelet
      therapy was not associated with a significant change in target lesion
      revascularization (TLR) and target vessel revascularization (TVR) at short-term
      follow-up. However, TLR and TVR were significantly reduced at midterm follow-up
      (relative risk 0.57, 95% confidence interval 0.39 to 0.84, and relative risk
      0.62, 95% confidence interval 0.47 to 0.83, respectively). Data regarding TLR and
      TVR at long-term follow-up were limited and inconclusive. We did not find a
      difference in myocardial infarction, mortality, or major bleeding at any follow
      up duration. In conclusion, the addition of cilostazol to dual antiplatelet
      therapy after percutaneous coronary intervention has favorable effects on TLR and
      TVR at 1 to 12 months, with no differences in adverse outcomes at any follow-up
      duration.

PMID- 22381163
TI  - Acute kidney injury (AKI) and risk of readmissions in patients with heart
      failure.
AB  - Heart failure (HF) contributes to a high rate of hospitalizations. Acute kidney
      injury (AKI), with or without chronic kidney disease (CKD), is a common
      complication in patients with HF. The link between AKI and the risk for
      readmission for repeat episodes of HF is not well studied. In this study, 6,535
      patients discharged with primary diagnoses of HF derived from a statewide
      inpatient database were examined. The association between AKI, with and without
      CKD, and risk for 30-day readmission with HF was assessed. Logistic regression
      was used to test the relations between predictor variables and outcomes. The mean
      age was 73.8 +/- 14.6 years, and 51% of patients (n = 3,351) were women. AKI
      occurred in 6.5% of patients during the index hospitalization, whereas 16% had
      CKD. Nine hundred seventy-seven patients (15%) required readmission within 30
      days for HF. Index hospital mortality was 1.7% in those without AKI or CKD
      compared to 11% and 13% in those with AKI without and with CKD, respectively (p
      <0.0001). Patients with AKI had a 30-day readmission rate of 21%, compared to 14%
      in those without AKI (p <0.0001). On multivariate analysis, AKI without CKD was
      associated with the highest risk for readmission (odds ratio 1.81, 95% confidence
      interval 1.35 to 2.39) compared to those with neither of the 2 diagnoses. In
      conclusion, patients with HF who have AKI experience a high rate of 30-day
      readmission for repeat episodes of HF. Reducing the risk for AKI, and follow-up
      monitoring after AKI, may improve care and reduce health care costs in patients
      with HF.

PMID- 22381164
TI  - Impact of statin therapy on late target lesion revascularization after sirolimus
      eluting stent implantation (from the CREDO-Kyoto Registry Cohort-2).
AB  - Therapeutic strategies preventing late target lesion revascularization (TLR)
      after drug-eluting stent implantation have not been yet adequately investigated.
      In 13,087 consecutive patients undergoing first percutaneous coronary
      intervention in the CREDO-Kyoto Registry Cohort-2, we identified 10,221 patients
      who were discharged alive after implantation of sirolimus-eluting stents (SESs)
      only (SES stratum 5,029) or bare-metal stents (BMSs) only (BMS stratum 5,192).
      Impact of statin therapy at time of discharge from the index hospitalization on
      early (within the first year) and late (1 year to 4 years) TLR, was assessed in
      the SES stratum (statin group 2,735; nonstatin group 2,294) and in the BMS
      stratum (statin group 2,576; nonstatin group 2,616). Despite a significantly
      lower incidence of early TLR (7.8% vs 22.2%, p <0.0001), SES use compared to BMS
      use was associated with a significantly higher incidence of late TLR (7.7% vs
      3.0%, p <0.0001). In the SES and BMS strata, the incidence of early TLR was
      similar regardless of statin use. In the SES stratum, the incidence of late TLR
      was significantly lower in the statin group than in the nonstatin group (6.1% vs
      9.6%, p = 0.002), whereas no significant difference was found in the BMS stratum
      (2.6% vs 3.3%, p = 0.38). After adjusting confounders, risk for late TLR
      significantly favored statin use in the SES stratum (hazard ratio 0.73, 95%
      confidence interval 0.54 to 0.98, p = 0.04), whereas the risk decrease was not
      significant in the BMS stratum (hazard ratio 0.74, 95% confidence interval 0.46
      to 1.20, p = 0.23). In conclusion, statin therapy at hospital discharge was
      associated with a significantly lower risk for late TLR after SES implantation.

PMID- 22381165
TI  - Compartment-specific expression of plasminogen activator inhibitor-1 correlates
      with severity/outcome of murine polymicrobial sepsis.
AB  - INTRODUCTION: Plasminogen activator inhibitor type 1 (PAI-1) co-induces septic
      coagulopathy. We aimed to characterize spatiotemporal PAI-1 gene/protein changes
      occurring in acute sepsis and tested whether PAI-1 fluctuations correlate with
      sepsis severity and early outcome. MATERIALS AND METHODS: Female mice underwent
      cecal ligation and puncture (CLP) in three experiments. I: mild (23 G needle) CLP
      to compare circulating PAI-1 to its organ gene expression within 0-24h. II: mild
      or severe (17 G) CLP to asses differences in PAI-1 organ-specific expression and
      in coagulation/fibrinolysis. III: moderate (18 G) CLP to characterize circulating
      PAI-1 in survivors (SUR), and to retrospectively compare it to dying (DIE) mice.
      RESULTS: In mild sepsis, the trajectory of circulating PAI-1 (1089 ng/ml peak at
      24h) was identical to PAI-1 gene expression in the left cranial vena cava (LCVC;
      39-fold peak at 24h). PAI-1 expression rise was immediate (60-fold at 6h) and
      sustained in the liver, but marginal in the kidney, lungs and heart. Body
      temperature decrease correlated with the PAI-1 expression increase in the liver
      (rho = -0.79), and blood (protein, rho = -0.53). Regardless of severity, PAI-1
      gene expression remained unaltered except the LCVC where it was >3-fold higher in
      17G (vs. 23 G). Severe sepsis extended activated partial thromboplastin/pro
      thrombin time and increased circulating PAI-1, while antithrombin and fibrinogen
      decreased at 6 and/or 24h (vs. 23 G). Within 24h of death, circulating PAI-1 in
      DIE was >3-fold higher versus SUR. CONCLUSIONS: Polymicrobial sepsis caused a
      gradual circulating PAI-1 release and highly variable gene expression response
      pattern in organs. Only circulating PAI-1 and PAI-1 expression in the LCVC
      correlated with response severity and/or outcome.

PMID- 22381166
TI  - Focus on molecules: lysyl oxidase.

PMID- 22381168
TI  - Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive
      review of the current literature.
AB  - CONTEXT: The heterogeneity of upper tract urothelial carcinoma (UTUC) biology and
      prognosis, as well as the presence of different treatment options, makes the
      clinical decision-making process extremely challenging. OBJECTIVE: Provide an
      overview of the currently available prognostic factors for UTUC, focusing on
      clinical and pathologic characteristics, as well as on molecular markers.
      EVIDENCE ACQUISITION: A systematic literature search was conducted using the
      PubMed, Scopus, and Embase databases to identify original articles, review
      articles, and editorials regarding prognostic factors in patients with UTUC.
      Keywords included urothelial carcinoma, renal pelvis, ureter, upper urinary tract
      urothelial carcinoma, upper urinary tract transitional cell carcinoma, prognosis,
      prognostic factors, markers, and survival. Articles published between 2000 and
      2011 were reviewed and selected with the consensus of all the authors. EVIDENCE
      SYNTHESIS: Prognostic factors can be divided into four different categories:
      preoperative/clinical factors, intraoperative/surgical factors,
      postoperative/pathologic factors, and molecular markers. Because of the rarity of
      the disease, only a small amount of level 1 evidence information from prospective
      randomized trials is available. Conversely, several single-institutional and
      multi-institutional studies have been published providing level 3 evidence
      information on various prognostic factors. Tumor stage and grade represent the
      best-established predictors of prognosis in patients with UTUC, but controversies
      still exist regarding the prognostic impact of tumor location and tumor necrosis.
      Several promising biomarkers have also been evaluated, but further studies
      evaluating their prognostic role are still needed. Finally, few prognostic models
      have been developed to provide clinicians with accurate estimates of the outcome
      of interest. CONCLUSIONS: In the past few years, several prognostic factors have
      been identified to help clinicians dealing with patients with UTUC in the
      decision-making process. However, well-designed multi-institutional studies are
      still needed to provide stronger evidence and to promote the use of these
      prognostic factors in clinical practice.

PMID- 22381169
TI  - Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or
      adjuvant therapy: long-term results in 1100 patients.
AB  - BACKGROUND: The optimal treatment strategy for muscle-invasive bladder cancer
      (BCa) remains controversial. OBJECTIVE: Better define the long-term outcomes of
      radical cystectomy (RC) alone for BCa and determine the impact of pathologic
      downstaging after transurethral resection in a large and homogeneous single
      center series. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 1100 patients
      undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant
      therapy for urothelial carcinoma of the bladder between January 1, 1986, and
      December 2009 was evaluated. Patients with other than metastases to the pelvic
      lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic
      characteristics, and long-term outcomes were evaluated. Follow-up was obtained
      until December 2009 with a median of 38 mo and a completeness of 96.5%.
      INTERVENTION: RC with PLND; urinary diversion with ileal neobladder whenever
      possible. MEASUREMENTS: Primary end points were disease-specific survival (DSS),
      recurrence-free survival (RFS), and overall survival (OS) according to the tumor
      stage of the RC specimen versus the maximum tumor stage. The log-rank test was
      used to compare subgroups. RESULTS AND LIMITATIONS: The 30-d (90-d) mortality
      rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and
      65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS
      rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0:
      36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the
      prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b
      pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC
      specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49%
      female and 80% male patients received an ileal neobladder. CONCLUSIONS: This
      contemporary and homogeneous single-center series found acceptable OS, DFS, and
      RFS for patients undergoing RC. Pathologic downstaging had a significant impact
      on survival.

PMID- 22381170
TI  - Overexpression of programmed death ligand 1 in dendritic cells inhibits
      allogeneic lymphocyte activation in mice.
AB  - BACKGROUND: Co-stimulatory molecules are pivotal for T cell activation. It is
      increasingly recognized that programmed death ligand 1 (PD-L1) is a novel co
      stimulatory molecule, which raises the question as to whether PD-L1 regulates T
      cell responses. This study aimed to investigate the inhibitory effects of PD-L1
      on T cell activation. MATERIALS AND METHODS: We constructed a transgenic vector
      containing the complete PD-L1 gene, which interacts with the inhibitory receptor
      PD-1 in T cell-mediated immune activation. Donor dendritic cells (DCs) derived
      from C57BL/6 mice were transfected with PD-L1 and mixed with allogeneic,
      recipient T cells from BALB/c mice. The T cell activation was determined by the
      MTT assay and T cell proliferation was determined using carboxyfluoroscein
      succinimidyl ester (CFSE)-labeling following in vitro mixed leukocyte reactions.
      RESULTS: The expression of PD-L1 protein in PD-L1-transfected DCs was 47.97% +/-
      1.06%, compared with 4.66% +/- 0.76% and 5.30% +/- 0.60% in blank and negative
      controls, respectively (P < 0.05). PD-L1 protein was effectively expressed in
      DCs. Furthermore, in DCs stably transfected with PD-L1, T cell activation was
      significantly suppressed and T cell proliferation rate was decreased by 35%
      compared with untransfected DCs (P < 0.05). CONCLUSION: PD-L1 delivers an
      immunoinhibitory signal, suppressing T cell activation. Overexpression of PD-L1
      signaling induces tolerance, which presents a promising immunotherapeutic
      approach for long-term graft acceptance.

PMID- 22381171
TI  - Dynamics of hepatic gene expression profile in a rat cecal ligation and puncture
      model.
AB  - BACKGROUND: Sepsis remains a major clinical challenge in intensive care units.
      The difficulty in developing new and more effective treatments for sepsis
      exemplifies our incomplete understanding of the underlying pathophysiology of it.
      One of the more widely used rodent models for studying polymicrobial sepsis is
      cecal ligation and puncture (CLP). While a number of CLP studies investigated the
      ensuing systemic inflammatory response, they usually focus on a single time point
      post-CLP and therefore fail to describe the dynamics of the response.
      Furthermore, previous studies mostly use surgery without infection (herein
      referred to as sham CLP, SCLP) as a control for the CLP model, however, SCLP
      represents an aseptic injurious event that also stimulates a systemic
      inflammatory response. Thus, there is a need to better understand the dynamics
      and expression patterns of both injury- and sepsis-induced gene expression
      alterations to identify potential regulatory targets. In this direction, we
      characterized the response of the liver within the first 24 h in a rat model of
      SCLP and CLP using a time series of microarray gene expression data. METHODS:
      Rats were randomly divided into three groups: sham, SCLP, and CLP. Rats in SCLP
      group are subjected to laparotomy, cecal ligation, and puncture while those in
      CLP group are subjected to the similar procedures without cecal ligation and
      puncture. Animals were saline resuscitated and sacrificed at defined time points
      (0, 2, 4, 8, 16, and 24 h). Liver tissues were explanted and analyzed for their
      gene expression profiles using microarray technology. Unoperated animals (Sham)
      serve as negative controls. After identifying differentially expressed probesets
      between sham and SCLP or CLP conditions over time, the concatenated data sets
      corresponding to these differentially expressed probesets in sham and SCLP or CLP
      groups were combined and analyzed using a "consensus clustering" approach.
      Promoters of genes that share common characteristics were extracted and compared
      with gene batteries comprised of co-expressed genes to identify putatative
      transcription factors, which could be responsible for the co-regulation of those
      genes. RESULTS: The SCLP/CLP genes whose expression patterns significantly
      changed compared with sham over time were identified, clustered, and finally
      analyzed for pathway enrichment. Our results indicate that both CLP and SCLP
      triggered the activation of a proinflammatory response, enhanced synthesis of
      acute-phase proteins, increased metabolism, and tissue damage markers. Genes
      triggered by CLP, which can be directly linked to bacteria removal functions,
      were absent in SCLP injury. In addition, genes relevant to oxidative stress
      induced damage were unique to CLP injury, which may be due to the increased
      severity of CLP injury versus SCLP injury. Pathway enrichment identified pathways
      with similar functionality but different dynamics in the two injury models,
      indicating that the functions controlled by those pathways are under the
      influence of different transcription factors and regulatory mechanisms.
      Putatively identified transcription factors, notably including cAMP response
      element-binding (CREB), nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB), and signal transducer and activator of transcription (STAT),
      were obtained through analysis of the promoter regions in the SCLP/CLP genes. Our
      results show that while transcription factors such as NF-kappaB, homeodomain
      transcription factor (HOMF), and GATA transcription factor (GATA) were common in
      both injuries for the IL-6 signaling pathway, there were many other transcription
      factors associated with that pathway which were unique to CLP, including forkhead
      (FKHD), hairy/enhancer of split family (HESF), and interferon regulatory factor
      family (IRFF). There were 17 transcription factors that were identified as
      important in at least two pathways in the CLP injury, but only seven
      transcription factors with that property in the SCLP injury. This also supports
      the hypothesis of unique regulatory modules that govern the pathways present in
      both the CLP and SCLP response. CONCLUSIONS: By using microarrays to assess
      multiple genes in a high throughput manner, we demonstrate that an inflammatory
      response involving different dynamics and different genes is triggered by SCLP
      and CLP. From our analysis of the CLP data, the key characteristics of sepsis are
      a proinflammatory response, which drives hypermetabolism, immune cell activation,
      and damage from oxidative stress. This contrasts with SCLP, which triggers a
      modified inflammatory response leading to no immune cell activation, decreased
      detoxification potential, and hyper metabolism. Many of the identified
      transcription factors that drive the CLP-induced response are not found in the
      SCLP group, suggesting that SCLP and CLP induce different types of inflammatory
      responses via different regulatory pathways.

PMID- 22381172
TI  - Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the
      inhibition of PKC-alpha in breast cancer cells.
AB  - BACKGROUND: Berberine (BBR) is one of the major alkaloids, and it has been
      reported to have a variety of pharmacologic effects, including inhibition of cell
      cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9
      expressions, which are predictors of metastasis and invasion in breast cancer
      cells. METHODS: MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR.
      The levels of MMP-1 protein and PKC-alpha phosphorylation were detected by
      Western blotting. MMP-9 protein expression was detected by gelatin zymography.
      Cell cycle was analyzed by FACS analysis. PKC-alpha knock-down was examined by
      PKC-alpha siRNA transfection. RESULTS: The basal levels of both the MMP-1 and MMP
      9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In
      contrast, TPA, which is a tumor promoter, significantly increased the levels of
      the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer
      cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein
      expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1
      and MMP-9 expressions were completely decreased by Go6983 and PKC-alpha siRNA,
      respectively. TPA-induced PKC-alpha phosphorylation was dose-dependently
      decreased by BBR treatment. CONCLUSION: The TPA-induced PKC-alpha phosphorylation
      is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by
      berberine. Therefore, we suggest that berberine may be used as a candidate drug
      for the inhibition of metastasis of human breast cancer.

PMID- 22381173
TI  - NBD peptides protect against ischemia reperfusion after orthotopic liver
      transplantation in rats.
AB  - BACKGROUND: NBD (NEMO binding domain) peptides could selectively inhibit the
      inflammation induced NF-kappaB activity, while sparing the protective functions
      of basal NF-kappaB activity. The aim of this study was to determine whether NBD
      peptides inhibited the transcriptional activity of nuclear factor-kappaB (NF
      kappaB) during liver transplant ischemia-reperfusion injury (IRI), without
      affecting its basal function. MATERIALS AND METHODS: Sprague Dawley (SD) rats
      were performed orthotropic liver transplantation according to the Kamada
      technique. Donors were given NBD peptides (8 mg/kg, intraperitoneal) 2 h before
      surgery (n = 24) and the controls were treated with the same volume of
      physiologic saline (n = 24). An additional 16 animals in normal condition (did
      not undergo any surgery) were also divided into two groups and given the same
      treatment as above to assess the effect of NBD peptides on basal function. We
      analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF
      alpha), IKK (IkappaB kinase) complex phosphorylation, IkappaBalpha degradation,
      NF-kappaB transcriptional activity, apoptosis, and performed a morphologic study
      of liver tissues at 3, 6, and 24 h after portal vein reperfusion and in normal
      condition (n = 8). RESULTS: Pretreatment with NBD peptides significantly improved
      liver function, attenuating liver parenchymal cell damage, apoptosis by down
      regulating TNF-alpha level, inhibiting IKK complex phosphorylation, IkappaBalpha
      degradation, and NF-kappaB transcriptional activity, but had no effect in normal
      condition. CONCLUSION: NBD peptides attenuated hepatic IRI by preventing NF
      kappaB activation, without affecting basal NF-kappaB activity.

PMID- 22381174
TI  - An overview of trends in animal poisoning cases in the United States: 2002-2010.
AB  - Veterinary toxicology is a constantly evolving field. The authors use the ASPCA
      Animal Poison Control Center's medical record database to examine recent trends
      in veterinary toxicology/animal poisoning incidents received from 2002 to 2010.
      The demographics of animals exposed to potentially harmful substances, the types
      of substances ingested, changes/emerging trends in substance exposures, and
      trends in therapies used to treat exposures are discussed.

PMID- 22381175
TI  - Investigative diagnostic toxicology and the role of the veterinarian in pet food
      related outbreaks.
AB  - Due to the potential implications of food-related illnesses in animals,
      recognition of pet food-related outbreaks is one of the many crucial roles of the
      veterinarian. This article describes the veterinarian's role in investigating and
      reporting food-related illnesses in cats and dogs. Recommendations regarding
      taking thorough case histories, appropriate sample collection, effective use of
      veterinary diagnostic laboratories, and recommendations for reporting such
      illnesses are described.

PMID- 22381176
TI  - Pet food recalls and pet food contaminants in small animals.
AB  - Most pet foods are safe, but incidents of chemical contamination occur and lead
      to illness and recalls. There were 11 major pet food recalls in the United States
      between 1996 and 2010 that were due to chemical contaminants or misformulations:
      3 aflatoxin, 3 excess vitamin D3, 1 excess methionine, 3 inadequate thiamine, and
      1 adulteration with melamine and related compounds and an additional 2 warnings
      concerning a Fanconilike renal syndrome in dogs after ingesting large amounts of
      chicken jerky treat products. This article describes clinical findings and
      treatment of animals exposed to the most common pet food contaminants.

PMID- 22381177
TI  - Use of intravenous lipid emulsions for treating certain poisoning cases in small
      animals.
AB  - Intravenous lipid emulsion (ILE) infusions have become an emerging treatment
      modality in managing intoxications of veterinary patients. The advantages of ILE
      include an apparent wide margin of safety, relatively low cost, long shelf-life,
      and ease of administration. Based on limited case and anecdotal reports, ILEs
      have shown promise in the management of toxicoses from a variety of lipophilic
      agents, including drugs and pesticides. More studies are needed to determine
      optimum dosing regimens and identify potential adverse effects from the antidotal
      use of ILE in veterinary medicine.

PMID- 22381178
TI  - Calcium channel blocker toxicity in dogs and cats.
AB  - The widespread use and availability of calcium channel blockers in human and
      veterinary medicine pose a risk for inadvertent pet exposure to these
      medications. Clinical signs can be delayed by many hours after exposure in some
      cases, with hypotension and cardiac rhythm changes (bradycardia, atrioventricular
      block, or tachycardia) as the predominant signs. Prompt decontamination and
      aggressive treatment using a variety of modalities may be necessary to treat
      patients exposed to calcium channel blockers. The prognosis of an exposed patient
      depends on the severity of signs and response to treatment.

PMID- 22381179
TI  - Management of attention-deficit disorder and attention-deficit/hyperactivity
      disorder drug intoxication in dogs and cats.
AB  - Two types of drugs are generally used for treating attention
      deficit/hyperactivity disorder or attention-deficit disorder in humans:
      amphetamines or similar stimulants and the nonamphetamine atomoxetine. We
      describe the toxicity and treatment of both amphetamines and similar medications
      and atomoxetine in dogs and cats. Amphetamine intoxication can cause life
      threatening stimulatory signs. Treatment is aimed at preventing absorption,
      controlling the stimulatory signs, and protecting the kidneys; prognosis is
      generally good. Atomoxetine also has a fast onset of action; stimulatory signs
      such as hyperactivity and tachycardia are often seen. There are little published
      data about treatment of atomoxetine toxicity in cats and dogs.

PMID- 22381180
TI  - Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs
      and cats.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of heterogeneous
      compounds extensively used in both human and veterinary medicine for their
      antipyretic, anti-inflammation, and analgesic properties. NSAIDs consist of a
      wide range of pharmacologically active agents with different chemical structures,
      with similar therapeutic and adverse effects. The ASPCA Animal Poison Control
      Center received 22,206 NSAID incidents in dogs and cats (3% of total cases; dogs
      [15,823] and cats [1244]) during 2005 to 2010. This is roughly equivalent to 4%
      NSAID incidents reported in humans. The most common NSAID involved was ibuprofen,
      followed by aspirin, naproxen, deracoxib, meloxicam, diclofenac, piroxicam,
      indomethacin, nabumetone, and etodolac. This article provides a brief overview of
      classification, mechanism of action, pharmacologic and toxicologic properties,
      and treatment information involving frequently encountered human and veterinary
      NSAIDs in dogs and cats.

PMID- 22381181
TI  - Xylitol toxicosis in dogs.
AB  - The sugar alcohol xylitol is a popular sweetener used in gums, candies, and baked
      goods. While xylitol has a wide margin of safety in people and most mammalian
      species, when ingested by dogs it is believed to stimulate excessive insulin
      secretion leading to severe hypoglycemia, potentially followed by acute hepatic
      failure and coagulopathies. Additional clinical findings may include
      thrombocytopenia, hypokalemia, and hyperphosphatemia. The prognosis for recovery
      in dogs that develop uncomplicated hypoglycemia is generally good with prompt and
      aggressive veterinary care.

PMID- 22381183
TI  - Toxicology of newer insecticides in small animals.
AB  - In the broadest definition, a pesticide (from fly swatters to chemicals) is a
      substance used to eliminate a pest. Newer insecticides are much safer to the
      environment, humans and non target species. These insecticides are able to target
      physiologic differences between insects and mammals, resulting in greater
      mammalian safety. This article briefly reviews toxicity information of both older
      insecticides like organophosphates (OPs), carbamates, pyrethrins, and
      pyrethroids, as well as some newer insecticides.

PMID- 22381182
TI  - Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P
      glycoprotein in dogs and cats.
AB  - The macrocyclic lactones (MLs) are parasiticides able to kill a wide variety of
      arthropods and nematodes. They have a high margin of safety for labeled
      indications, and ivermectin has become the best-selling antiparasitic in the
      world. Dogs of certain breeds and mixtures of those breeds have a defect in the
      ABCB1 gene (formerly MDR1 gene) that results in a lack of functional P
      glycoprotein, which leads to accumulation of the MLs in the central nervous
      system and a higher risk of adverse effects when exposed. There is no specific
      antidote for ML toxicosis so the most important part of treatment is good
      supportive care.

PMID- 22381184
TI  - Common rodenticide toxicoses in small animals.
AB  - This article focuses on the 3 most commonly used rodenticide types:
      anticoagulants, bromethalin, and cholecalciferol. It is important to verify the
      active ingredient in any rodenticide exposure. Many animal owners may use the
      term "D-con" to refer to any rodenticide regardless of the actual brand name or
      type of rodenticide. The EPA released their final ruling on rodenticide risk
      mitigation measures in 2008 and all the products on the market had to be
      compliant by June 2011, changing to consumer products containing either first
      generation anticoagulants or nonanticoagulants including bromethalin and
      cholecalciferol. These regulations are likely to cause an increase in the number
      of bromethalin and cholecalciferol cases.

PMID- 22381185
TI  - Toxicology of explosives and fireworks in small animals.
AB  - Intoxication with explosives or fireworks in dogs or cats is not common, but
      serious toxicosis can result from exposure to different types of explosives
      depending on the chemical class of explosive involved. This article will discuss
      the different types of materials/chemicals, clinical signs of toxicosis, and
      their treatment. Despite the complexities of explosives and plethora of different
      devices currently in use worldwide, the toxic potential is more easily explained
      by looking at the relatively short list of chemical classes used to produce these
      materials. This article combines structurally similar explosives into different
      groups and focuses on the toxicity of the most commonly available explosives.

PMID- 22381186
TI  - Mushroom poisoning cases in dogs and cats: diagnosis and treatment of
      hepatotoxic, neurotoxic, gastroenterotoxic, nephrotoxic, and muscarinic
      mushrooms.
AB  - Of the several thousand species of mushrooms found in North America, less than
      100 are toxic. Species in the genus Amanita are responsible for the vast majority
      of reported mushroom poisonings. In general, the number of reported mushroom
      poisonings in animals is low, most likely because toxicology testing is available
      for a limited number of mushroom toxins and thus many cases are not confirmed or
      reported. Also, only a limited number of mushrooms are submitted for
      identification purposes. Mushroom intoxications require tremendous efforts from
      clinicians and toxicologists in terms of making a diagnosis and treatment, and
      management is challenging.

PMID- 22381187
TI  - Differential diagnosis of common acute toxicologic versus nontoxicologic illness.
AB  - This table outlines common toxicologic versus nontoxicologic rule outs based on
      clinical abnormalities seen in an acutely ill animal. The purpose is to provide
      an initial guideline for considering toxicologic versus nontoxicologic rule outs
      when a patient is presented to a practicing veterinarian. Major clinical
      abnormalities followed by common toxicologic rule outs and non-toxicologic rule
      outs have been listed so that practicing veterinarians can narrow down an
      etiology quickly. Based on history, physical examination findings, and blood work
      changes, once a reasonable etiology has been narrowed down or established, the
      reader is encouraged to review a more detailed discussion on management of the
      particular poisoning or disease listed in this or other references.

PMID- 22381188
TI  - Common reversal agents/antidotes in small animal poisoning.
AB  - Different antidotes counteract the effect of a toxicant in several different
      ways. Antidotes can reverse, decrease, or prevent action of a toxicant. They can
      also help in achieving stabilization of vital signs, directly or indirectly, and
      promote excretion of a toxicant. However, overreliance on an antidote can be
      unrealistic and dangerous. While expectations of rapid recovery from antidotes
      are usually high, in a real life situation, there are many impediments in
      achieving this goal. The timing of its use, availability, cost, and sometimes
      adverse effects from the antidote itself can influence the results and outcome of
      a case. The majority of toxicants do not have a specific antidote therapy
      indicated and patients in these cases equally benefit from supportive care. In
      this chapter, commonly used antidotes and reversal agents in small animals are
      listed in a table form. The table lists generic name along with brand name of an
      antidote/reversal agent whenever available, main indications for their use, and
      provides comments or cautions in their use as needed. After stabilizing the
      patient and establishing the etiology, the clinicians must review more detailed
      management of that particular toxicant discussed here or in other references.

PMID- 22381189
TI  - Common toxicologic issues in small animals.

PMID- 22381190
TI  - Low maternal retinol as a risk factor for schizophrenia in adult offspring.
AB  - BACKGROUND: Prenatal micronutrient deficiency has been linked to later
      development of schizophrenia among offspring; however, no study has specifically
      investigated the association between vitamin A and this disorder. Vitamin A is an
      essential nutrient which is required by the early embryo and fetus for gene
      expression and regulation, cell differentiation, proliferation and migration.
      Previous work suggests that vitamin A deficiency in the second trimester may be
      particularly relevant to the etiopathogenesis of neurobehavioral phenotypes some
      of which are observed in schizophrenia. METHODS: We examined whether low maternal
      vitamin A levels in the second trimester are associated with the risk of
      schizophrenia and other schizophrenia spectrum disorders (SSD) in the Prenatal
      Determinants of Schizophrenia study; third trimester vitamin A levels were also
      examined in relation to SSD. The cases were derived from a population-based birth
      cohort; all cohort members belonged to a prepaid health plan. Archived maternal
      serum samples were assayed for vitamin A in cases (N=55) and up to 2 controls per
      case (N=106) matched on length of membership in the health plan, date of birth
      (+/-28 days), sex, and gestational timing and availability of archived maternal
      sera. RESULTS: For the second trimester, low maternal vitamin A, defined as
      values in the lowest tertile of the distribution among controls, was associated
      with a greater than threefold increased risk of SSD, adjusting for maternal
      education and age (OR=3.04, 95% CI=1.06, 8.79, p=.039). No association between
      third trimester maternal vitamin A and SSD was observed. CONCLUSIONS: Although
      further investigations are warranted, this is the first birth cohort study to our
      knowledge to report an association between low maternal vitamin A levels and SSD
      among offspring.

PMID- 22381191
TI  - Early environmental exposures influence schizophrenia expression even in the
      presence of strong genetic predisposition.
AB  - There are few studies of environmental factors in familial forms of
      schizophrenia. We investigated whether childhood adversity or environmental
      factors were associated with schizophrenia in a familial sample where
      schizophrenia is associated with the NOSA1P gene. We found that a cumulative
      adversity index including childhood illness, family instability and cannabis use
      was significantly associated with narrow schizophrenia, independent of NOSA1P
      risk genotype, previously measured childhood trauma, covariates and familial
      clustering (adjusted odds ratio (95% confidence interval)=1.55 (1.01, 2.38)). The
      results provide further support that early environmental exposures influence
      schizophrenia expression even in the presence of strong genetic predisposition.

PMID- 22381192
TI  - Dissociation and social cognition in schizophrenia spectrum disorder.
AB  - While there is emerging evidence that dissociation is linked with trauma history
      and possibly symptoms in schizophrenia, it remains unclear whether dissociation
      represents a symptom dimensions in its own right in schizophrenia and as such is
      uniquely related to other features of illness. To explore this issue the current
      study sought to find out whether dissociation was uniquely related to an index of
      social cognition closely linked to social functioning, namely affect recognition.
      We hypothesized that dissociation would be linked with affect recognition because
      symptoms of dissociation may uniquely disrupt processes which are expected to be
      needed for correctly recognizing emotions. The sample contained 49 participants
      diagnosed with a schizophrenia spectrum disorder who were in a non-acute phase of
      disorder. Participants were concurrently administered the Bell-Lysaker Emotion
      Recognition Task, the Dissociative Experiences Scale, the Post Traumatic Stress
      Disorder Checklist and the Positive and Negative Symptoms Scale. Stepwise linear
      regression analyses were performed in which dissociative symptoms were forced to
      enter after the other symptoms in order to predict deficits in affect
      recognition. These analyses revealed that greater levels of dissociative symptoms
      predicted poorer recognition of negative emotions over and above that of
      positive, negative, cognitive and PTSD symptoms. Results are consistent with the
      possibility that dissociation represents a unique dimension o f psychopathology
      in schizophrenia which may be linked to function.

PMID- 22381193
TI  - Syndesmotic fixation in supination-external rotation ankle fractures: a
      prospective randomized study.
AB  - BACKGROUND: This study was designed to assess whether transfixion of an unstable
      syndesmosis is necessary in supination-external rotation (Lauge-Hansen SE/Weber
      B)-type ankle fractures. METHODS: A prospective study of 140 patients with
      unilateral Lauge-Hansen supination-external rotation type 4 ankle fractures was
      done. After bony fixation, the 7.5-Nm standardized external rotation (ER) stress
      test for both ankles was performed under fluoroscopy. A positive stress
      examination was defined as a difference of more than 2 mm side-to-side in the
      tibiotalar or tibiofibular clear spaces on mortise radiographs. If the stress
      test was positive, the patient was randomized to either syndesmotic transfixion
      with 3.5-mm tricortical screws or no syndesmotic fixation. Clinical outcome was
      assessed using the Olerud-Molander scoring system, RAND 36-Item Health Survey,
      and Visual Analogue Scale (VAS) to measure pain and function after a minimum 1
      year of followup. RESULTS: Twenty four (17%) of 140 patients had positive
      standardized 7.5-Nm ER stress tests after malleolar fixation. The stress view was
      positive three times on tibiotalar clear space, seven on tibiofibular clear
      space, and 14 times on both tibiotalar and tibiofibular clear spaces. There was
      no significant difference between the two randomization groups with regards to
      Olerud-Molander functional score, VAS scale measuring pain and function, or RAND
      36-Item Health Survey pain or physical function at 1 year. CONCLUSION: Relevant
      syndesmotic injuries are rare in supination-external rotation ankle fractures,
      and syndesmotic transfixion with a screw did not influence the functional outcome
      or pain after the 1-year followup compared with no fixation.

PMID- 22381194
TI  - Comparison of magnetic resonance imaging to physical examination for syndesmotic
      injury after lateral ankle sprain.
AB  - BACKGROUND: Clinical assessment of syndesmotic injury usually consists of two
      tests: the ankle external rotation test and squeeze test. This study sought to
      determine the sensitivity and specificity of both for syndesmotic injury
      secondary to lateral ankle sprain. METHODS: Fifty-six patients with sprained
      ankles underwent clinical examination for syndesmotic injury with the
      aforementioned tests. Clinical findings were compared against magnetic resonance
      imaging (MRI) of the ankle. Sprains were graded on anatomical and functional
      classification scales, and correlation and agreement between both scales were
      assessed. RESULTS: The MRI prevalence of syndesmotic injury in patients with
      lateral ankle sprains was 17.8%. Sensitivity and specificity were 30% and 93.5%
      for the squeeze test, and 20% and 84.8% for the external rotation test,
      respectively. Using the anatomical scale for sprain grading, 40% of syndesmotic
      injuries occurred in Grade I, 40% in Grade II, and 20% in Grade III sprains. Ten
      percent of patients with syndesmotic injury had no lateral ligament injury on
      MRI, 70% had injury of the anterior talofibular (ATFL) ligament, and 20% had
      injury to the ATFL and calcaneofibular (CFL). CONCLUSION: The sensitivity of the
      squeeze test and external rotation test was low, suggesting that physical
      examination often fails to diagnose syndesmotic injury. Conversely, specificity
      was very high; nearly all patients with a positive test actually had syndesmotic
      injury. Severity of ankle sprain was not associated with prevalence of
      syndesmotic injury.

PMID- 22381195
TI  - Paratenonitis of the foot and ankle in young female dancers.
AB  - BACKGROUND: In their pursuit of excellence, dancers continually face the risk of
      injuries, such as paratenonitis. This attests to the strong need for preventive
      action, which is possible only if major risk factors are identified. The aim of
      the present descriptive study was to determine the association between risk
      factors and paratenonitis in young recreational female dancers. METHODS: One
      thousand eighty-two non-professional female dancers, aged 8 to 16 years, were
      screened. The risk factors considered for paratenonitis were: joint range of
      motion (ROM), body structure, anatomic anomalies, dance technique, and dance
      discipline. All dancers were clinically examined for current ankle/foot
      paratenonitis. RESULTS: Ninety-three dancers (8.6%) manifested a paratenonitis at
      the ankle or foot joints. ROM such as hyper ankle plantarflexion and hyper hip
      external rotation, false dance technique, and hours of practice per week were
      found to be associated with increased rate of injury. Regression analysis
      indicated that dancers with paratenonitis had greater hip external rotation ROM
      compared to dancers without paratenonitis. No association with injury was found
      with age of onset of menarche, body structure, and anatomic anomalies such as
      scoliosis. CONCLUSION: Precautionary steps, such as screening for joint ROM and
      dance technique, may reduce the risk of dance injury. Furthermore, our results
      led to a very significant justification of the dance maxim ''don't force your
      natural joint ROM and especially your 'turnout' position,'' as it could increase
      your chance to develop paratenonitis.

PMID- 22381196
TI  - Combined medial and lateral anatomic ligament reconstruction for chronic
      rotational instability of the ankle.
AB  - BACKGROUND: This study aimed to extend knowledge on the arthroscopic evaluation
      of the unstable ankle joint and the outcome of ligament reconstruction on
      rotational instability. In contrast to previous studies, we investigated the
      combined repair of lateral and medial ligaments. METHODS: Ninety-six patients
      underwent medial and lateral ligament reconstruction between 2006 and 2008, 81 of
      whom, with a mean age of 31.9 (range, 14 to 44) years, completed the 12-month
      followup and were therefore included in this study (Table 1). Clinical,
      radiographic, and concomitant arthroscopic examination was performed prior to the
      ligament stabilization. Postoperative followup included clinical and radiographic
      evaluation after 3, 6, and 12 months. RESULTS: Arthroscopy showed a lesion of the
      anterior fibulotalar ligament (AFTL),  calcaneofibular ligament (CFL), and
      tibiocalcanear ligament (TCL) (Deep part of deltoid ligament complex) in 67
      patients. An avulsion of the proximal insertion point of the ATTL was
      additionally found in 14 cases. Clinical results 3 months after surgery showed a
      significant increase in the AOFAS-Hindfoot Score as well as a significant
      decrease of the Visual Analogue-Scale for pain (VAS) (p < 0.0001). This outcome
      persisted at the 12-month examination. CONCLUSION: Rotational instability of the
      ankle joint in most cases has an injury of the lateral ligaments and a component
      of the deltoid, the TCL, but rarely with a combined lesion of the TCL and the
      anterior tibiotalar ligament (ATTL) (Superficial part of deltoid ligament
      complex). The combined lateral and medial ligament reconstruction with an anchor
      technique had a good clinical outcome with high patient satisfaction with few
      complications.

PMID- 22381197
TI  - Subtalar joint arthroereisis in the management of pediatric flexible flatfoot: a
      critical review of the literature.
AB  - BACKGROUND: Pediatric flexible flatfoot is a common deformity for which a small,
      but significant number undergo corrective surgery. Arthroereisis is a technique
      for treating flexible flatfoot by means of inserting a prosthesis into the sinus
      tarsi. The procedure divides opinion in respect of both its effectiveness and
      safety. METHODS: A database search up until 2010 was used to find articles
      regarding arthroereisis in pediatric patients. We summarized the findings of this
      study. RESULTS: Seventy-six studies were identified. Eight  of the nine
      radiographic parameters reported show significant improvement following
      arthroereisis reflecting both increased static arch height and joint congruency.
      Calcaneal inclination angle demonstrated the least change with only small
      increases following arthroereisis. Arthroereisis remains associated with a number
      of complications including sinus tarsi pain, device extrusion, and under
      correction. Complication rates range between 4.8% and 18.6% with unplanned
      removal rates between 7.1% and 19.3% across all device types. CONCLUSION: Current
      evidence is limited to consecutive case series or ad hoc case reports. Limited
      evidence exists to suggest that devices may have a more complex mode of action
      than simple motion blocking or axis altering effects. The interplay between
      osseous alignment and dynamic stability within the foot may contribute to the
      effectiveness of this procedure. Although literature suggests patient
      satisfaction rates of between 79% to 100%, qualitative outcome data based on
      disease specific, validated outcome tools may improve current evidence and permit
      comparison of future study data.

PMID- 22381198
TI  - Critical review of self-reported functional ankle instability measures.
AB  - BACKGROUND: Since functional ankle instability (FAI) lacks a "gold standard''
      measure, a variety of self-reported ankle instability measures have been created.
      The purpose of this study was to determine which ankle instability measure
      identifies individuals who meet a minimum acceptable criterion for FAI. METHODS:
      Participants volunteered from a large university population which included 242
      participants (104 males, 138 females; 21.4 +/- 1.4 years). The predictor
      variables were seven ankle instability questionnaires: Ankle Instability
      Instrument (AII), Ankle Joint Functional Assessment Tool (AJFAT), Chronic Ankle
      Instability Scale (CAIS), Cumberland Ankle Instability Tool (CAIT), Foot and
      Ankle Ability Measure (FAAM), Foot and Ankle Instability Questionnaire (FAIQ),
      and Foot and Ankle Outcome Score (FAOS). The outcome variable (MC_FAI) was
      created based on the minimum acceptable criteria for FAI. This was established as
      at least one ankle sprain and an episode of giving way. Data were modeled using
      chi-square and multinomial logistic regression. RESULTS: The regression model
      revealed all of the questionnaires were more useful at identifying participants
      who did not meet the minimum criteria for FAI (No MC_FAI = 95.7%, MC_FAI = 55.6%,
      overall = 84.6%). Based on the Wald criterion, the full model was reduced to the
      CAIT, AII, and FAAM. The reduced model revealed the CAIT (X(2) = 8.756, p =
      0.003) and AII (X(2) = 31.992, p = 0.001) as the only variables that had a
      significant relationship with the outcome variable. CONCLUSION: The model
      illustrates no single measure was able to predict if individuals met the
      minimally accepted criteria for FAI. However, a significantly accurate prediction
      of ankle stability status was produced by combining the CAIT and AII. CLINICAL
      RELEVANCE: Based on the results we recommend that researchers and clinicians use
      both the CAIT and AII to determine ankle stability status.

PMID- 22381199
TI  - Tendoscopic treatment of intrasheath subluxation of the peroneal tendons.
AB  - BACKGROUND: Intrasheath subluxation of the peroneal tendons does not have an
      injury of the proximal retinaculum. The aim of this study was to describe the
      tendoscopic technique and preliminary results. METHODS: Six patients with
      intrasheath subluxation of the peroneal tendons were treated tendoscopically. All
      patients had preoperative pain and a clicking sensation at the lateral
      retromalleolar area. Mean followup was 18.3 (range, 14 to 24) months. These six
      patients included three males and three females, with a mean age of 23.5 (range,
      18 to 33) years. The AOFAS and Visual Analog Score for pain were used to evaluate
      the patients. RESULTS: During tendoscopy, two patients had a peroneus quartus
      tendon which was removed; three had a low-lying peroneus brevis muscle that was
      resected; and in two cases deepening of the peroneal groove was performed. At
      followup, all patients reported excellent results, without pain or clicking
      sensation. The mean AOFAS score increased from 79 to 99, and Visual Analog Score
      at followup was 0 in four patients and 1 in two patients. CONCLUSION: Tendoscopic
      treatment of these pathologies led to improved function in a less aggressive
      manner than open surgery.

PMID- 22381200
TI  - Gastrocnemius contracture caused by traumatic injury without fracture: a case
      report.

PMID- 22381201
TI  - Validation and precision of model-based radiostereometric analysis (MBRSA) for
      total ankle arthroplasty.
AB  - BACKGROUND: The goal of this study was to design a RSA marker insertion protocol
      to evaluate the stability of the bone-implant interface of a TAA prosthesis, and
      to validate that this marker insertion protocol can be combined with MBRSA
      technology to provide clinically adequate precision in assessing the micromotion
      of the TAA prosthesis. METHODS: The MobilityTM Total Ankle System was used in
      this study. A marker placement protocol was developed with a Phantom Protocol.
      The Improved Marker Placement Protocol was used in 20 patients. Postoperative RSA
      double exams were taken. Condition Numbers (CN) were used to assess the marker
      distribution. The system precision was defined as the standard deviation of the
      double exams (MTE, MRE). MBRSA software was used to evaluate the double exams.
      RESULTS: The RSA marker insertion technique for the 20 {?it in vivo} cases
      provided satisfactory results. CNs in all subjects but one were below 50 mm(-1)
      and implied a desirable marker configuration. The tibial sphere MTE was 0.07 mm
      and the talar was 0.09 mm. The talar MRE was 0.51 degrees. CONCLUSION: The system
      precision for these {?it in vivo} TAA implants was within the normal range
      identified by RSA studies, and comparable to the existing TAA RSA studies. This
      study demonstrated a reliable RSA marker insertion technique in both the tibia
      and talus. The study confirms that the insertion and MBRSA technique allows the
      typical high precision demonstrated in other RSA studies (standard deviation less
      than or equal to 0.25 mm or 0.6 degrees). CLINICAL RELEVANCE: This method may
      allow more accurate assessment of prosthetic subsidence clinically.

PMID- 22381202
TI  - Association of hindfoot ligament tears and osteochondral lesions.
AB  - BACKGROUND: This study aimed to identify the prevalence of ligament and joint
      surface anatomy variants, ligament tears, and osteochondral lesions (OCLs) in the
      hindfoot. These data were used to identify associations between anatomic variants
      or ligament tears and OCLs. METHODS: Seventy-two cadaver hindfoot specimens were
      examined. Hindfoot ligament presence, number of ligament fascicles, variable
      ligament attachment sites, ligament tears, presence of joint facets, variable
      joint surface shape, and the location and grade of OCLs were identified in each
      specimen. The data were analyzed for significant associations between variables.
      RESULTS: Fourteen of the 30 studied ligaments were always present and 14 had
      variable number of fascicles. The lateral talocalcaneal and dorsolateral
      calcaneocuboid ligaments had varying positional attachments. Osteochondral
      lesions were present in 86% of specimens with the majority in the talocrural
      joint. Of the 235 lesions identified, 31 were grade 3 or above. Ligament tears
      occurred in 2% of all ligaments observed. Tears in the lateral talocalcaneal,
      medial calcaneocuboid, and dorsolateral calcaneocuboid ligaments were associated
      with an increased number of hindfoot OCLs. CONCLUSION: We demonstrated the
      prevalence of morphologic ligament and joint surface variants, ligament tears,
      and osteochondral lesions in the hindfoot. Tears in ligaments stabilizing the
      calcaneocuboid joint were implicated in an increase in hindfoot joint damage.
      CLINICAL RELEVANCE: We believe anatomic studies can be used to clarify the
      association between traumatic injuries and their sequelae.

PMID- 22381203
TI  - Surgical strategies: hallux rigidus surgical techniques.

PMID- 22381204
TI  - siRNA LNCs--a novel platform of lipid nanocapsules for systemic siRNA
      administration.
AB  - Several siRNA (small interfering RNA) therapeutics are undergoing clinical trials
      for cancer, respiratory diseases or macular degeneration, but most are
      administrated locally. In order to overcome the different barriers to attain an
      efficient siRNA action after systemic administration, nanocarriers able to carry
      and protect siRNA are awaited. With this aim, we developed a new platform of
      siRNA lipid nanocapsules (LNCs) using different cationic lipids, combining the
      properties of LNCs (siRNA protection and targeting) and lipoplexes (efficient
      siRNA delivery into the cell). The formulation was revealed to contain different
      compartments. A siRNA quantification method based on UV spectroscopy was
      developed to locate and quantify siRNA in each compartment. All in all, these
      novel siRNA LNCs presented sizes of about 55 nm with a neutral surface charge and
      siRNA encapsulation efficiencies up to 65% representing appropriate
      characteristics for systemic administration.

PMID- 22381205
TI  - Genetic variants in microRNA biogenesis pathway genes are associated with semen
      quality in a Han-Chinese population.
AB  - MicroRNA biogenesis genes have been confirmed involved in lots of diseases. This
      study evaluated the role of genetic variants in microRNA biogenesis genes in
      semen quality and idiopathic male infertility. Seven single-nucleotide
      polymorphisms (SNP) of DICER1 (rs13078, rs1057035 and rs12323635) and DROSHA
      (rs10719, rs2291109, rs17409893 and rs642321) were determined by TaqMan probes
      and SNPstream in 667 eligible infertile men and 419 fertile controls. Semen
      quality analysis was performed by computer-assisted sperm analysis. It was found
      that genetic variants of rs12323635 was associated with idiopathic male
      infertility. Additionally, in strategy analysis, the rs12323635 C allele might
      decrease the risk of oligozoospermia (OR 0.42, 95% CI 0.26-0.66; P=0.0002). The
      rs642321 TT genotype may have a higher risk of oligozoospermia (OR 2.38, 95% CI
      1.34-4.25; P=0.003). These significant differences were retained after Bonferroni
      correction. The results showed that variants of DICER1 and DROSHA may modify the
      risk of abnormal semen parameters, which could result in male infertility.
      MicroRNA have been confirmed involved in lots of diseases. To our knowledge, few
      studies have elucidated the role of genetic variants in microRNA biogenesis genes
      in semen quality and idiopathic male infertility, although microRNA is
      indispensable in normal spermatogenesis. In this original study, we evaluated the
      potential impact of the polymorphisms in microRNA biogenesis genes on the risk of
      abnormal semen quality based on 667 infertile patients and 419 controls, and
      provided the first evidence that polymorphism in rs12323635 in DICER1 may modify
      the risk of abnormal semen parameters, which could result in male infertility.

PMID- 22381207
TI  - Assisted reproductive technologies in the reproductive management of small
      ruminants.
AB  - In modern agriculture, assisted reproductive technologies are being used for out
      of season oestrus induction, enhancement of reproductive performance and genetic
      improvement. In addition, they can have substantial contribution in preservation
      of endangered species or breeds, as well as in eradication programs of various
      diseases. While their applications are widespread in cattle, in small ruminants
      it is almost restricted to artificial insemination. The main limitations of a
      wider application in small ruminants are the naturally occurring anoestrus
      period, the variability of response to superovulatory treatments, the
      fertilisation failure and the need of surgery for collection and transfer of
      gametes and embryos. Nonetheless, during the last 30 years, considerable progress
      has been made in sheep and goat embryo technologies, especially in the fields of
      oestrus synchronisation, superovulation and in vitro embryo production. This
      paper reviews the status of assisted reproductive technologies in sheep,
      analysing the prospects offered by recent advances in in vivo and in vitro embryo
      production from mature and juvenile lambs.

PMID- 22381206
TI  - Spatial and temporal distribution of Oct-4 and acetylated H4K5 in rabbit embryos.
AB  - Rabbit is a unique species to study human embryology; however, there are limited
      reports on the key transcription factors and epigenetic events of rabbit embryos.
      This study examined the Oct-4 and acetylated H4K5 (H4K5ac) patterns in rabbit
      embryos using immunochemistry staining. The average intensity of the Oct-4 signal
      in the nuclei of the whole embryo spiked upon fertilization, then decreased until
      the 8-cell stage and increased afterwards until the compact morula (CM) stage. It
      decreased thereafter from the CM stage to the early blastocyst (EB) stage, with a
      minimum at the expanded blastocyst (EXPB) stage and came back to a level similar
      to that of the CM-stage embryos in the hatching blastocysts (HB). The Oct-4
      signal was observed in both the inner cell mass (ICM) and the trophectoderm (TE)
      cells of blastocysts. The average H4K5ac signal intensity of the whole embryo
      increased upon fertilization, started to decrease at the 4-cell stage, reached a
      minimum at the 8-cell stage, increased again at the EXPB stage and peaked at the
      HB stage. While TE cells maintained similar levels of H4K5ac throughout the
      blastocyst stages, ICM cells of HB showed higher levels of H4K5ac than those of
      EB and EXPB. Understanding key genetic and epigenetic events during early embryo
      development will help to identify factors contributing to embryo losses and
      consequently improve embryo survival rates. As a preferred laboratory species for
      many human disease studies such as atherosclerosis, rabbit is also a pioneer
      species in the development of several embryo biotechnologies, such as IVF,
      transgenesis, animal cloning, embryo cryopreservation and embryonic stem cells.
      However, there are limited reports on key transcription factors and epigenetic
      events of rabbit embryos. In the present study, we documented the temporal and
      spatial distribution of Oct-4 protein and H4K5 acetylation during early embryo
      development using the immunostaining approach. We also compared the patterns of
      these two important biomarkers between the inner cell mass (ICM) and the
      trophectoderm (TE) cells in blastocyst-stage embryos. Our findings suggest that a
      combination of Oct-4, H4K5ac and possibly other biomarkers such as Cdx-2 is
      needed to accurately identify different lineages of cells in morula and
      blastocyst stage rabbit embryos. Importantly, we revealed a novel wave of Oct-4
      intensity change in the ICM cells of rabbit blastocysts. The signal was high at
      the early blastocyst stage, reached a minimum at the expanded blastocyst stage
      and returned to a high level at the hatching blastocyst stage. We hypothesize
      that the signal may have reflected the regulation of Oct-4 through enhancer
      switching and therefore may be related to cell lineage formation in rabbit
      embryos. These findings enrich our understanding on key genetic and epigenetic
      programming events during early embryo development in rabbits.

PMID- 22381208
TI  - Failed Fontan heart transplant candidates with preserved vs impaired ventricular
      ejection: 2 distinct patient populations.

PMID- 22381209
TI  - Quality of life in pediatric heart transplant recipients: a comparison with
      children with and without heart disease.
AB  - BACKGROUND: Little is known about the quality of life (QOL) of children with
      heart disease who undergo life-saving surgery. The aim of this multicenter study
      was to examine self- and parent-reported QOL outcomes in pediatric heart
      transplant recipients. METHODS: Pediatric heart transplant recipients/families (n
      = 174) from 7 transplant programs completed the Pediatric Quality of Life
      Inventory Generic Core Scales and Cardiac Module. Scores for the heart transplant
      sample were compared with non-transplant patients who had undergone conventional
      cardiac surgery and with a healthy child sample. Within the cardiac surgery
      group, heart disease/surgery was further categorized by severity/complexity.
      RESULTS: Heart transplant recipients were a mean age of 10.6 +/- 4.7 years at a
      mean time post-transplant of 6.0 +/- 4.1 years. By both self-report and parent
      proxy report, mean scores for heart transplant recipients were significantly
      lower than those in healthy children for physical and psychosocial QOL, including
      emotional and social functioning (p < 0.001), with 31.3% self-reporting
      significantly impaired psychosocial QOL scores. By self-report, there were no
      significant differences in emotional and social mean scores between the
      transplant and cardiac surgery groups. Transplant recipients reported
      significantly fewer cardiac symptoms than children with cardiac surgery (p <
      0.01). Their self-reported school functioning scores were not significantly
      different from children with moderate to severe disease. CONCLUSION: Although
      pediatric heart transplant recipients experience significant symptomatic
      improvement, they remain at-risk for impaired psychosocial QOL, similar to
      children with residual or palliated heart disease. Assessment is needed to
      identify children at-risk and improve psychosocial outcomes.

PMID- 22381210
TI  - Recoverability of renal functions after relief of partial ureteric obstruction of
      solitary kidney: impact of ferulic acid.
AB  - What's known on the subject? and What does the study add? It is known that the
      kidney damage continues even after release of ureteric obstruction. This study
      found that giving ferulic acid, antioxidant, after release of ureteric
      obstruction enhanced the recovery of kidney functions in solitary kidney.
      OBJECTIVE: To evaluate the effect of ferulic acid (FA) on the recovery of renal
      function and renal damage after relief of partial ureteric obstruction (PUO) of a
      solitary kidney. METHODS: Male mongrel dogs (n = 32) were classified into three
      groups: sham (eight), control (12) and study (12). A right nephrectomy was
      carried out and dogs in the study and control groups were subjected to 4 weeks of
      PUO. Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC)
      were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief
      of obstruction. Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide
      dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of
      apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial
      fibrosis in the kidney were evaluated at the end of experiment. RESULTS: Ferulic
      acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26%
      and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks'
      obstruction. In addition, FA caused a significant decrease in MDA and a
      significant increase in GSH and SOD. Ferulic acid also significantly reduced the
      interstitial fibrosis, and caspase 3 expression, and significantly increased the
      expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the
      obstruction. CONCLUSION: Ferulic acid enhances the recoverability of renal
      function and minimizes the renal damage through reduction of oxidative stress,
      tubular apoptosis and the interstitial fibrosis in the solitary kidney after
      relief of PUO.

PMID- 22381211
TI  - Apple polyphenols extract (APE) improves colon damage in a rat model of colitis.
AB  - BACKGROUND AND AIM: Searching for alternative therapies that are effective, safe
      and less expensive of those currently used for ulcerative colitis, we
      investigated the efficacy of a polyphenol extract from apple in rat colitis.
      METHODS: Rats with trinitrobenzensulphonic acid-induced colitis were treated
      daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX
      2, TNF-alpha, tissue transglutaminase and calpain in colon mucosa samples were
      assessed by reverse transcription-polymerase chain reaction and western blot
      analyses. To ascertain the role of tissue transglutaminase in mucosal healing,
      wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase
      activity inhibitor). RESULTS: Colitis was associated with increased COX-2, TNF
      alpha, calpain, and tissue transglutaminase mRNA. The protein expression of COX
      2, TNF-alpha and calpain was increased whilst tissue transglutaminase was
      decreased. Apple extract treatment reduced the severity of colitis (p<0.05) and
      restored all the considered biomarkers at the baseline level. Apple polyphenols
      reduced the degradation of tissue transglutaminase protein occurring through
      calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h
      showing intense immunoreactivity for tissue transglutaminase. CONCLUSION: The
      efficacy of apple extract is mediated by its effects on COX-2 and TNF-alpha. The
      unbalance between calpain and tissue transglutaminase may play a role in colonic
      damage and future therapeutic interventions in ulcerative colitis can target this
      mechanisms.

PMID- 22381213
TI  - Asymmetric synthesis of 1,3-dioxolanes by organocatalytic formal [3 + 2]
      cycloaddition via hemiacetal intermediates.
AB  - A novel asymmetric formal [3 + 2] cycloaddition reaction for the synthesis of 1,3
      dioxolanes using cinchona-alkaloid-thiourea-based bifunctional organocatalysts is
      reported. The reaction proceeds via the formation of hemiacetal intermediates
      between gamma-hydroxy-alpha,beta-unsaturated ketones and aldehydes.

PMID- 22381214
TI  - Diagnosis and treatment of rathke cleft cysts: a perspective.

PMID- 22381215
TI  - Does sacrifice of the C2 root benefit C1-2 arthrodesis?

PMID- 22381216
TI  - Treating atlantooccipital dislocation in very young children and infants: solving
      the Archimedean spiral.

PMID- 22381217
TI  - Preventing venous thromboembolism after thoracic or thoracolumbar spinal fusion.

PMID- 22381218
TI  - Combination of de novo assembly of massive sequencing reads with classical repeat
      prediction improves identification of repetitive sequences in Schistosoma
      mansoni.
AB  - The genome of the parasitic platyhelminth Schistosoma mansoni is composed of
      approximately 40% of repetitive sequences of which roughly 20% correspond to
      transposable elements. When the genome sequence became available, conventional
      repeat prediction programs were used to find these repeats, but only a fraction
      could be identified. To exhaustively characterize the repeats we applied a new
      massive sequencing based strategy: we re-sequenced the genome by next generation
      sequencing, aligned the sequencing reads to the genome and assembled all multiple
      hit reads into contigs corresponding to the repetitive part of the genome. We
      present here, for the first time, this de novo repeat assembly strategy and we
      confirm that such assembly is feasible. We identified and annotated 4,143 new
      repeats in the S. mansoni genome. At least one third of the repeats are
      transcribed. This strategy allowed us also to identify 14 new microsatellite
      markers, which can be used for pedigree studies. Annotations and the combined
      (previously known and new) 5,420 repeat sequences (corresponding to 47% of the
      genome) are available for download (http://methdb.univ-perp.fr/downloads/).

PMID- 22381219
TI  - LDL uptake by Leishmania amazonensis: involvement of membrane lipid microdomains.
AB  - Leishmania amazonensis lacks a de novo mechanism for cholesterol synthesis and
      therefore must scavenge this lipid from the host environment. In this study we
      show that the L. amazonensis takes up and metabolizes human LDL(1) particles in
      both a time and dose-dependent manner. This mechanism implies the presence of a
      true LDL receptor because the uptake is blocked by both low temperature and by
      the excess of non-labelled LDL. This receptor is probably associated with
      specific microdomains in the membrane of the parasite, such as rafts, because
      this process is blocked by methyl-beta-cyclodextrin (MCBD). Cholesteryl ester
      fluorescently-labeled LDL (BODIPY-cholesteryl-LDL) was used to follow the
      intracellular distribution of this lipid. After uptake it was localized in large
      compartments along the parasite body. The accumulation of LDL was analyzed by
      flow cytometry using FITC-labeled LDL particles. Together these data show for the
      first time that L. amazonensis is able to compensate for its lack of lipid
      synthesis through the use of a lipid importing machinery largely based on the
      uptake of LDL particles from the host. Understanding the details of the molecular
      events involved in this mechanism may lead to the identification of novel targets
      to block Leishmania infection in human hosts.

PMID- 22381221
TI  - Antimicrobial stewardship: a collaborative partnership between infection
      preventionists and health care epidemiologists.
AB  - It is clear that the widespread and injudicious use of antimicrobials has greatly
      increased the presence of MDROs that threaten the health of all. There is
      worldwide acknowledgement that this threat is growing, and that prudent use of
      antimicrobials combined with infection prevention can prevent harm and improve
      patient safety. Antimicrobial stewardship programs must harness the talents of
      all members of the health care team to effectively identify the organism,
      determine its susceptibility, institute any precautions required, and prescribe
      the narrowest-acting antibiotic that will destroy it. IPs/HEs play a pivotal role
      in this approach, by assisting with early organism and infected patient
      identification, by promoting compliance with standard and transmission-based
      precautions and other infection prevention strategies such as care bundle
      practices, hand hygiene, and by educating staff, patients, and visitors.

PMID- 22381222
TI  - Certification in infection control matters: Impact of infection control
      department characteristics and policies on rates of multidrug-resistant
      infections.
AB  - BACKGROUND: The study objective is to describe infection control policies aimed
      at multidrug-resistant organisms (MDRO) in California hospitals and assess the
      relationship among these policies, structural characteristics, and rates of
      methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant
      Enterococcus (VRE) bloodstream infections and Clostridium difficile infections.
      METHODS: Data on infection control policies, structural characteristics, and MDRO
      rates were collected through a 2010 survey of California infection control
      departments. Bivariate and multivariable Poisson and negative binomial
      regressions were conducted. RESULTS: One hundred eighty hospitals provided data
      (response rate, 54%). Targeted MRSA screening upon admission was reported by the
      majority of hospitals (87%). The majority of hospitals implemented contact
      precautions for confirmed MDRO and C difficile patients; presumptive
      isolation/contact precautions for patients with pending screens were less
      frequently implemented. Few infection control policies were associated with lower
      MDRO rates. Hospitals with a certified infection control director had
      significantly lower rates of MRSA bloodstream infections (P < .05). CONCLUSION:
      Although most California hospitals are involved in activities to decrease MDRO,
      there is variation in specific activities utilized with the most focus placed on
      MRSA. This study highlights the importance of certification and its significant
      impact on infection rates. Additional research is needed to confirm these
      findings.

PMID- 22381223
TI  - Prospective, randomized in vivo comparison of a dual-active waterless antiseptic
      versus two alcohol-only waterless antiseptics for surgical hand antisepsis.
AB  - BACKGROUND: This study aimed to demonstrate the value of adding an active level
      of a persistent antimicrobial agent, such as chlorhexidine gluconate (CHG), to an
      alcohol-based surgical hand antiseptic. METHODS: The persistence of 3 waterless,
      brushless alcohol-based surgical hand antiseptics, including one product
      containing CHG, was compared. The test products were applied a total of 12 times
      over 5 days. Samples of aerobic bacteria were collected on days 1 and 5, on both
      days immediately after drying and 6 hours later, using the glove juice technique.
      Relative suppression of regrowth was compared using t tests. RESULTS: Using an
      equivalence margin of 20%, the alcohol plus CHG product showed noninferiority to
      the alcohol-only products at all sampling points and, based on significantly
      lower bacterial regrowth (P = .026), superior persistence to the alcohol-only
      products after 6 hours of glove wear. CONCLUSIONS: Given the primary objective of
      surgical hand antisepsis of reducing resident skin flora for the duration of the
      surgical procedure, using an alcohol-based hand antiseptic containing CHG appears
      to be the most appropriate choice for maintaining microbial levels as low as
      possible for as long as possible.

PMID- 22381225
TI  - [Mass spectrometry in the clinical microbiology laboratory].
AB  - Infectious diseases are still a cause of high mortality and morbidity rates.
      Current microbiological diagnostic methods are based on culture and phenotypic
      identification of isolated microorganisms, which can be obtained in about 24-48
      h. Given that the microbiological identification is of major importance for
      patient management, new diagnostic methods are needed in order to detect and
      identify microorganisms in a timely and accurate manner. Over the last few years,
      several molecular techniques based on the amplification of microbial nucleic
      acids have been developed with the aim of reducing the time needed for the
      identification of the microorganisms involved in different infectious processes.
      On the other hand, mass spectrometry has emerged as a rapid and consistent
      alternative to conventional methods for microorganism identification. This review
      describes the most widely used mass spectrometry technologies -matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray
      ionization time-of-flight (ESI-TOF)-, both for protein and nucleic acid analysis,
      as well as the commercial platforms available. Related publications of most
      interest in clinical microbiology are also reviewed.

PMID- 22381226
TI  - [Molecular confirmation of an especially difficult to diagnose case of leprosy].

PMID- 22381227
TI  - The expression of sex steroid synthesis and inactivation enzymes in subcutaneous
      adipose tissue of PCOS patients.
AB  - Modulation of sex steroid pre-receptor in adipose tissue is important for the
      development of metabolic diseases, but its roles in the pathogenesis of
      polycystic ovary syndrome (PCOS) has not been fully characterized. Herein we
      compared the expression of key sex steroid converting enzymes in the subcutaneous
      adipose tissue (SAT) between patients with PCOS and the matched controls. Most of
      the sex steroid converting enzymes were highly expressed in the SAT, except
      17alpha-hydroxylase (CYP17A1). Compared with the controls, PCOS patients showed
      significantly higher levels of 3beta-hydroxysteroid dehydrogenase1-2 (3beta-HSD1
      2), aldo-keto reductase 1C 1-3 (AKR1C1-3) and leptin, but lower level of P450
      aromatase and 5alpha-reductase 1. Interestingly, leptin was positively correlated
      to AKR1C2 expression and negatively to 5alpha-reductase1 as well as peroxisome
      proliferator-activated receptor gamma (PPARgamma). In summary, the expression of
      enzymes synthesizing testosterone and enzymes inactivating DHT and progesterone
      was higher in SAT of PCOS patients compared to controls. Correlation analysis
      indicated that increased leptin expression may be negatively related to local DHT
      level. These data suggested that sex steroid converting enzymes expression was
      different in SAT of PCOS patients that might contribute to abnormal testosterone
      and leptin level of PCOS patients.

PMID- 22381228
TI  - GSTM1 null genotype as risk factor for late-onset Alzheimer's disease in Italian
      patients.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly. The
      causes of AD are very complex but there is general agreement about the existence
      of a link between Alzheimer's disease and oxidative stress. The Glutathione S
      transferases (GSTs) act to detoxify products of oxidation that cause damage to
      macromolecules. Particular attention has been focused on GST genes because
      polymorphisms are important determinants of disease risk. To evaluate if GSTA1,
      GSTM1, GSTP1, and GSTT1 genes are associated with LOAD we screened a case-control
      population (n=311). Differences in genotype distributions between AD patients and
      controls were found only for the GSTM1 null genotype (P<0.001). In addition, a
      logistic regression analysis also conferred a positive association between the
      GSTM1 null genotype and LOAD after adjustment for age and gender (OR=2.09;
      95%CI=1.31-3.35). The GSTM1 enzyme detoxifies substances such as exogenous and
      endogenous metabolites and plays a regulatory role in cellular signaling.
      Previous studies have highlighted that GSTM1 has a role in neurodegenerative
      disorders, but no data have associated the GSTM1 gene with AD risk. Our outcome
      suggests that the GSTM1 null genotype is a risk factor for AD in Italian
      patients.

PMID- 22381229
TI  - Quality of research and level of evidence in foot and ankle publications.
AB  - BACKGROUND: The quality of research and evidence to support medical treatments is
      under scrutiny from the medical profession and the public. This study examined
      the current quality of research and level of evidence (LOE) of foot and ankle
      surgery papers published in orthopedic and podiatric medical journals. METHODS:
      Two independent evaluators performed a blinded assessment of all foot and ankle
      clinical research articles (January 2010 to June 2010) from seven North American
      orthopedic and podiatric journals. JBJS-A grading system was used for LOE.
      Articles were assessed for indicators of study quality. The data was stratified
      by journal and medical credentials. RESULTS: A total of 245 articles were
      published, 128 were excluded based on study design, leaving 117 clinical research
      articles. Seven (6%) were Level I, 14 (12%) Level II, 18 (15%) Level III, and 78
      (67%) Level IV. The orthopedic journals published 78 studies on foot and ankle
      topics. Of the podiatric journals, the Journal of the American Podiatric Medical
      Association (JAPMA) published 12 clinical studies and the Journal of Foot and
      Ankle Surgery (JFAS) published 27, 21 (78%) of which were Level IV studies. When
      the quality of research was examined, few therapeutic studies used validated
      outcome measures and only 38 of 96 (40%) gathered data prospectively. Thirty
      (31%) studies used a comparison group. Eighty-seven articles (74%) were authored
      by a MD and 22 (19%) by a DPM. CONCLUSION: Foot & Ankle International (FAI)
      published higher quality studies with a higher LOE as compared to podiatry
      journals. Regardless of the journal, MDs produced the majority of published
      clinical foot and ankle research. Although improvements have been made in the
      quality of some clinical research, this study highlights the need for continued
      improvement in methodology within foot and ankle literature.

PMID- 22381230
TI  - Direct plantar approach to Henry's knot for flexor hallucis longus transfer.
AB  - BACKGROUND: Transfer of the flexor hallucis longus (FHL) tendon is an established
      method to replace a dysfunctional Achilles tendon. When using a single incision,
      the FHL tendon has to be transferred as a single stranded graft into the
      calcaneus and the distal FHL stump cannot be directly attached to the flexor
      digitorum longus tendon (FDL). Another concern with tendon retrieval is
      neurovascular damage. We report our results with a direct plantar approach for
      tendon harvest. METHODS: A direct plantar approach to the master knot of Henry
      with reattachment to its distal stump while protecting the medial plantar nerve
      was used allowing a double stranded FHL-transfer in 25 cases of a severely
      dysfunctional Achilles tendon in 24 consecutive patients. Patients were evaluated
      prospectively and at an average followup of 73 (range, 20 to 121) months.
      RESULTS: No wound healing problems and no lesion of the medial plantar nerve
      occurred. The subjective result was rated as excellent in 18 (72%), good in five
      (20%), and fair in one case (8%).The AOFAS hindfoot score averaged 95.4 (range,
      61 to 100) points and the AOFAS hallux score averaged 97.6 (range, 87 to 100)
      points. No loss of plantarflexion force was observed in the big toe as compared
      to the contralateral side. CONCLUSION: The plantar approach to Henry's knot
      allowed the use of a double stranded FHL transplant. The distal stump was
      attached to the FDL tendon to preserve flexion at the great toe without damaging
      to the medial plantar nerve.

PMID- 22381231
TI  - Proximal medial gastrocnemius release in the treatment of recalcitrant plantar
      fasciitis.
AB  - BACKGROUND: Isolated gastrocnemius contracture has been implicated as the cause
      of a number of foot and ankle conditions. Plantar fasciitis (PF) is one such
      condition that can be secondary to altered foot biomechanics as a result of
      gastrocnemius contracture. In this paper, we report our results with an isolated
      release of the proximal medial head of gastrocnemius for recalcitrant PF.
      METHODS: We prospectively followed a consecutive series of 21 heels in 17
      patients following a Proximal Medial Gastrocnemius Release (PMGR). PF was
      diagnosed clinically and confirmed radiologically in all cases. To be included,
      at least 1~year of conservative treatment must have been tried and an isolated
      gastrocnemius contracture confirmed clinically using Silfverskiold's test
      preoperatively. Outcome measures included a 5-point Likert scale as well as
      subjective and objective calf weakness assessments. Final followup was on average
      24 (range, 8 to 36) months after the surgery. RESULTS: Seventeen of the 21 heels
      (81%) reported total or significant pain relief following the surgery and none
      reported worsening of their symptoms. The majority did not have subjective or
      objective evidence of calf weakness. There were no 'major' complications and only
      one case that suffered a 'minor' complication. CONCLUSION: We believe a PMGR is a
      simple way of treating a patient with PF who has failed to respond to
      conservative management. In our series, the results were favorable, the recovery
      fast and the morbidity low.

PMID- 22381232
TI  - Ankle and hindfoot fusions: comparison of outcomes in patients with and without
      diabetes.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) are believed to have higher
      complication rates when undergoing ankle and hindfoot fusions, but data is
      lacking. The purpose of this study was to compare the postoperative outcomes of
      major foot and ankle arthrodeses in patients with and without DM. Another goal
      was to evaluate what effect glycemic control had on the outcomes of patients with
      diabetes. METHODS: A retrospective review of charts from operative years 2005 to
      2010 was performed. Inclusion criteria encompassed patients requiring major
      hindfoot and/or ankle fusion. Exclusion criteria included any patient who did not
      have at least 6-month followup. Seventy four patients with DM were matched with
      74 non-DM patients based on age, gender, and length of surgery. Significance was
      set at p < 0.05 with associated 95% confidence intervals. RESULTS: The overall
      complication rate was found to be significantly higher in patients with DM, a
      history of tobacco use, and peripheral neuropathy. The postoperative infection
      rate was found to be significantly higher in patients with DM, poor long-term
      glucose control (Hgb A1c levels greater than or equal to 7%), a history of
      tobacco use, peripheral artery disease, and peripheral neuropathy. Our rate of
      noninfectious complications was found to be significantly higher in patients with
      DM, poor short-term glucose control (a preoperative glucose greater than 200
      mg/dL), a history of tobacco use, and previous solid organ transplantation.
      Patients greater than or equal to 65 years of age were significantly associated
      with fewer overall complications and postoperative infections. CONCLUSION: This
      study confirmed our hypothesis that patients with DM were at increased risk for
      postoperative complications after foot and/or ankle arthrodesis when compared to
      patients without DM. A secondary finding of this study demonstrated patients with
      poor short- and long-term glucose control experienced more complications.

PMID- 22381233
TI  - Arthroscopic four-step treatment for chronic ankle instability.
AB  - BACKGROUND: Chronic lateral ankle instability is a condition of perception of
      giving way and persistent pain usually following multiple ankle sprains. Open
      reconstructive procedures carry the disadvantages of subtalar joint stiffness and
      potential morbidity at the harvesting site. Recently, arthroscopic treatment of
      chronic lateral ankle instability has been proposed in order to minimize
      invasiveness, reduce operating time, and allow a faster rehabilitation period.
      The purpose of our paper was to assess the outcomes in terms of postoperative
      recovery and return to sport following arthroscopic reconstruction of lateral
      ankle instability. METHODS: Ninety patients with chronic lateral ankle
      instability were treated at our Department from 2004 to 2009. Mean age was 32.4
      (range, 17 to 56) years. All patients underwent a four-step operative procedure,
      including: synovectomy, debridement of ATFL lesion borders, capsular shrinkage,
      and 21-day immobilization and nonweightbearing. RESULTS: Followup examination at
      an average of 4~years after surgery showed significant improvement of mean AOFAS
      scale (preoperative, 63.5; postoperative, 92.3; p < 0.001) and average Karlsson
      score (preoperative, 61.8; postoperative, 88.4; p < 0.001). Mean Tegner rating
      changed from 3.6 preoperatively to 4.9 at followup (p < 0.001). Articular
      stability as assessed by Sefton scale significantly improved from a preoperative
      value of 4.0 to 1.8 (p < 0.001). Most patients (96.6%) rated the success of their
      surgery as good to excellent. CONCLUSION: Based on our results, we propose
      arthroscopic treatment as a suitable option for moderate chronic ankle joint
      laxity in patients with a complete ATFL lesion.

PMID- 22381234
TI  - Functional outcome of endoscopic plantar fasciotomy.
AB  - BACKGROUND: The majority of cases of plantar fasciitis can be treated
      nonoperatively; however, a small number of patients remain refractory to
      nonoperative treatment and operative intervention is indicated. Historically,
      open treatment has been recommended, but more recently endoscopic plantar
      fasciotomy (EPF) has produced promising results. METHODS: Forty-eight patients
      (56 feet) were identified who underwent endoscopic plantar fasciotomy. Forty-one
      patients (49 feet) were available for followup. There were 15 men and 26 women,
      with an average age of 53.8 (range, 42 to 68) years. The mean followup time was
      49.5 (range, 6 to 142) months. An AOFAS Hind foot Scale was used for analysis.
      The influence of gender, duration of symptoms, severity of symptoms, and
      bilateral verses unilateral release were examined. RESULTS: Pain resolved
      completely in 37 feet, decreased in 11 feet, and increased in one foot. The mean
      postoperative AOFAS Hindfoot score improved 39 points (54 to 93, p < 0.001).
      Patients with severe symptoms achieved higher mean improvement than the moderate
      symptom group (p < 0.0001). Patients with symptoms greater than 24~months trended
      towards lower mean improvement and lower post operative AOFAS Hindfoot scores.
      Both gender and laterality did not significantly influence outcome. There was one
      superficial infection, one third and fourth metatarsal stress fracture in the
      same patient, and transient lateral hindfoot pain in five patients. CONCLUSION:
      EPF was an effective operation with reproducible results, low complication rate,
      and little risk of iatrogenic nerve injury with proper technique.

PMID- 22381235
TI  - Mobility of the first ray in various foot disorders.
AB  - BACKGROUND: Instability of the first ray has been proposed by Morton and others
      to be a major cause of several foot disorders, including hallux valgus, transfer
      metatarsalgia, lesser metatarsal stress fractures, and second metatarsophalangeal
      diseases. However, there are few studies to support these theories. In this
      study, we have used a simple device to measure first ray elevation and
      translation in a consecutive series of foot and ankle patients. We propose that
      mobility of the first ray will be increased in patients with hallux valgus,
      metatarsalgia, hallux rigidus, lesser metatarsal stress fractures, posterior
      tibial tendinitis, and interdigital neuromas. METHODS: Measurements of first ray
      translation and elevation were made in 345 feet in 315 patients. One or more
      pathologic diagnoses were recorded for each foot, and data was analyzed by a
      statistician. RESULTS: First ray mobility was increased in females compared to
      males. Patients with hallux valgus and metatarsalgia had greater mobility than
      other patients. Those feet with low arches showed greater mobility than those
      with high arches. Patients with hallux rigidus showed decreased mobility. We
      failed to find any differences for patients with stress fractures, posterior
      tibial tendinitis, or neuromas, but some of these groups may have had
      insufficient power. CONCLUSION: First ray translation and elevation are two
      different measures of medial column instability. Although they are distinct
      measures, they closely paralleled each other in this series. An association was
      found between increased first metatarsal elevation and several foot disorders.
      Although such an association does not prove causation, and it is likely other
      factors may play a role in many patients, this data does link instability of the
      first ray to some diseases. The decreased mobility seen in patients with hallux
      rigidus may offer new insights into the etiology of that disorder.

PMID- 22381236
TI  - Treatment of Lisfranc fracture-dislocations with primary partial arthrodesis.
AB  - BACKGROUND: The optimal method of treatment for Lisfranc fracture-dislocations
      remains controversial, and the role of primary partial arthrodesis for combined
      osseous-ligamentous Lisfranc injuries is unclear. This study reviewed the
      outcomes of Lisfranc injuries treated by primary partial arthrodesis. METHODS:
      Patients who underwent primary partial arthrodesis for a primarily ligamentous or
      combined osseous and ligamentous Lisfranc fracture-dislocation were reviewed
      retrospectively and assessed at followup according to radiographic, clinical and
      standardized patient-based outcomes. Twenty-five patients (12 ligamentous, 13
      combined), median age of 46 (range, 20 to 73) years, were followed for an average
      of 42 (range, 24 to 96) months. RESULTS: The average American Orthopedic Foot and
      Ankle Society (AOFAS) score was 81 points (scale 0 to 100), with patients in
      general losing points for mild pain, limitations of recreational activities, and
      fashionable footwear requirements. There was no statistical difference between
      ligamentous and combined injuries with regard to the physical or mental component
      scores on the SF-36. At latest followup, patients reported an average return to
      85% of their preinjury activity level (range, 50% to 100%). Twenty-one patients
      (84%) expressed satisfaction with their outcome and at latest followup, the mean
      visual analog pain scale (VAS) score was 1.8 out of 10 (range, 0 to 8). Three
      patients showed radiographic signs of post-traumatic arthritis of adjacent
      joints. CONCLUSION: Treatment of both primarily ligamentous and combined osseous
      and ligamentous lisfranc injuries with primary partial arthrodesis produced good
      clinical and patient-based outcomes.

PMID- 22381237
TI  - Responsiveness and validity of the SF-36, Ankle Osteoarthritis Scale, AOFAS Ankle
      Hindfoot Score, and Foot Function Index in end stage ankle arthritis.
AB  - BACKGROUND: We examined four commonly used scores, the SF-36, the Ankle
      Osteoarthritis Scale (AOS), the American Orthopaedic Foot and Ankle Society
      (AOFAS) Ankle Hindfoot Score, and the Foot Function Index (FFI) to determine
      their responsiveness and validity. METHODS: Patients with end stage ankle
      arthritis were recruited into a prospective multicenter cohort study and baseline
      and one year outcome scores were compared. The Standardized Response Mean and
      Effect Size for the AOS, AOFAS, and FFI were calculated and the three region- or
      disease-specific scores were compared with the SF-36 to determine their criterion
      validity. RESULTS: All four scores showed acceptable responsiveness, and when
      using the validated SF-36 as the standard the three region or disease specific
      scores all showed similar criterion validity. CONCLUSION: All four scores are
      responsive and can be considered for use in this population. The objective
      component of the AOFAS Ankle Hindfoot Score may make it harder to perform than
      the other three scores which have subjective components only, and as yet its
      objective component has not been shown to demonstrate reliability. We recommend
      use of a purely subjective score such as the Ankle Osteoarthritis Scale or Foot
      Function Index as the region- or disease-specific score of choice in this
      population. As the SF-36 shows acceptable responsiveness, using it alone could
      also be considered.

PMID- 22381238
TI  - The influence of heel height on frontal plane ankle biomechanics: implications
      for lateral ankle sprains.
AB  - BACKGROUND: Wearing high heel shoes is thought to increase an individual's
      likelihood of experiencing a lateral ankle sprain. The purpose of this study was
      to evaluate the influence of heel height on frontal plane kinematics, kinetics,
      and electromyographic (EMG) activity of the ankle joint during walking. METHODS:
      Eighteen healthy women participated. Three-dimensional kinematics, ground
      reaction forces, and EMG signals of the tibialis anterior (TA) and peroneus
      longus (PL) were recorded as subjects ambulated in high (9.5~cm) and low (1.3~cm)
      heel shoes at a self-selected walking velocity. Peak ankle plantarflexion, peak
      ankle inversion angle, and the peak ankle inversion moment during the stance
      phase of gait were evaluated. The EMG variables of interest consisted of the
      normalized average signal amplitude of the TA and PL during the first 50% of the
      stance phase. Paired t-tests were used to assess differences between the two shoe
      conditions. RESULTS: When compared to the low heel condition, wearing high heels
      resulted in significantly greater peak ankle plantarflexion and inversion angles
      (p < 0.001). In addition, the peak inversion moment and PL muscle activation was
      found to be significantly higher in the high heel condition (p < 0.001). No
      difference in TA muscle activity was found between shoe conditions (p = 0.30).
      CONCLUSION: The plantarflexed and inverted posture when wearing high heels may
      increase an individual's risk for experiencing a lateral ankle sprain. CLINICAL
      RELEVANCE: Data obtained from this investigation highlights the need for
      increased awareness and proper education related to the wearing of high heel
      shoes.

PMID- 22381239
TI  - Locked floating first metatarsal: open reduction and no fixation - case report.

PMID- 22381240
TI  - Osteosynthesis of talar body shear fractures assisted by hindfoot and subtalar
      arthroscopy: technique tip.

PMID- 22381241
TI  - Current concepts review: intra-articular fractures of the calcaneus.
AB  - 1) Intra-articular fractures of the calcaneus are associated with severe long
      term consequences for function and pain. The condition of the soft tissues is of
      paramount importance when determining the method of treatment,the timing of
      surgery, and the post-injury rehabilitation.2) Intra-articular fractures are
      difficult to fully evaluate with plain radiographs. Computed tomography may
      assist in assessing the fracture pattern and planning for surgery. The likelihood
      of a good to excellent outcome is increased when an anatomic reduction is
      obtained.3) The outcome after operative management is difficult to characterize
      and appears to be influenced by factors related to the fracture, the patient, and
      the experience of the institution where the patient obtains treatment.All these
      factors should be factors in the decision to operate, but no single factor
      reliably determines the most appropriate treatment.4) Open reduction and internal
      fixation through an extensile approach achieves acceptable results in carefully
      selected patients. The use of a limited exposure with minimally invasive
      techniques may decrease the incidence of wound complications. However, this
      option is technically demanding and the quality of the reduction achieved may be
      more difficult to obtain and determine intraoperatively. Open fractures should be
      promptly debrided. The choice of fixation after reduction is based on the
      surgeons assessment of the soft tissue and the risk of infection.5) Post
      traumatic arthritis of the subtalar joint is a common complication. Successful
      salvage can be achieved with a subtalar arthrodesis. However, these results may
      be influenced by the institution at which the initial management was rendered.

PMID- 22381242
TI  - FootForum: quality and patient safety.

PMID- 22381243
TI  - Re: a biomechanical analysis of a tensioned suture device in the fixation of the
      ligamentous Lisfranc injury by Pelt et al: Foot Ankle Int. 32(4): 422-31, 2011.

PMID- 22381245
TI  - From bench to MS bedside: challenges translating biomarker discovery to clinical
      practice.
AB  - A substantial need exists for developing and validating a range of biomarkers
      that would address a number of important unmet clinical needs in the MS field. In
      spite of considerable efforts over last years, very few putative biomarkers have
      been fully validated or successfully integrated into routine clinical practice.
      Here, we consider some of the main challenges that have limited such effective
      translation from biomarker discovery to the bedside in the context of MS, the
      prototypic chronic human CNS inflammatory illness. We will define the types of
      biomarkers that would be relevant for MS, identify their ideal attributes, and
      then discuss individual challenges and strategies to overcome them.

PMID- 22381244
TI  - Thrombin induces an inflammatory phenotype in a human brain endothelial cell
      line.
AB  - In this study, we utilized the human brain endothelial cell line, hCMEC/D3, to
      determine the effects of the coagulation factor, thrombin, on the human blood
      brain barrier (BBB). We show that thrombin increased the mRNA and cell surface
      levels of ICAM-1 and VCAM-1 in hCMEC/D3 cells. Thrombin similarly upregulated
      several chemokines implicated in human neurological conditions. Additionally, the
      paracellular permeability of the human BBB in vitro was also increased following
      thrombin treatment. Overall, this study demonstrates that thrombin can
      effectively induce an inflamed phenotype in an in vitro human BBB.

PMID- 22381247
TI  - Characterization of urine-derived cells from upper urinary tract in patients with
      bladder cancer.
AB  - OBJECTIVE: To investigate whether cells isolated from the upper urinary tract
      (UTCs) possess stem cell characteristics and could be an alternative cell source
      for patients with bladder cancer. Current tissue engineering approaches for
      urologic tissue regeneration require invasive tissue biopsies to obtain
      autologous cells, and these procedures are associated with potential
      complications, such as donor site morbidity. Recently, cells isolated from voided
      urine (VUCs) have been proposed as an alternative cell source for urologic tissue
      engineering. However, VUCs should not be used in patients with bladder cancer,
      because the voided urine sample could contain malignant cells. METHODS: Urine
      samples were collected from the upper urinary tract of 4 male patients with
      bladder cancer using a ureteral catheter. The samples were centrifuged and the
      pellets plated for primary culture. The cells were analyzed for colony-forming
      unit, proliferation rate, cytogenetics, stem cell characterization, and
      tumorigenicity. The results were compared with those of VUCs collected from 3
      healthy men. RESULTS: The UTCs were able to form colonies, had a greater
      proliferation rate than the VUCs, and had a normal karyotype without any
      chromosomal aberrations. The UTCs possessed stem cell characteristics (expression
      of CD44+, CD73+, CD90+, CD105+, SSEA4+) and expressed several markers for
      urothelial, smooth muscle, and endothelial cell lineages. The UTCs did not form
      teratoma when implanted into the subcapsular space of a mouse kidney. CONCLUSION:
      The UTCs possessed stem cell characteristics and can potentially be an
      alternative cell source for urologic tissue regeneration in patients with bladder
      cancer.

PMID- 22381246
TI  - Papillary renal cell carcinoma is associated with PTEN hamartoma tumor syndrome.
AB  - OBJECTIVE: To formally study the prevalence and histologic classification of
      renal cell carcinoma (RCC) in a series of patients with PTEN hamartoma tumor
      syndrome (PHTS). METHODS: We evaluated prevalence of RCC within a prospectively
      accrued series of 219 patients found to have pathogenic germline PTEN mutations.
      Clinical data including pathology reports were requested for all participants.
      Slides and tumor blocks were requested for central pathology re-review and
      immunohistochemistry (IHC) analysis. RESULTS: Nine patients were identified with
      RCC. Based on Surveillance Epidemiology and End Results (SEER) data 0.28 RCC
      cases were expected for the group, giving an overall age-adjusted Standardized
      Incidence Ratio (SIR) of 31.7 (95% CI 15.4-58.1, P < 0.001) with a higher sex
      adjusted SIR for females (46.7 vs 21.6 for males). Reported histology of each
      mutation positive patient's RCC was variable. However, on central pathology re
      review of eight patients, six examined lesions were determined to be of papillary
      subhistology (pRCC), with the other two patients' tumors consistent with the
      initial report of chromophobe RCC (chRCC). IHC demonstrated complete loss of PTEN
      protein in all PTEN mutation positive patients' pRCCs and patchy positivity in
      one chRCC. CONCLUSION: PHTS is a hereditary syndrome newly associated with pRCC,
      and PTEN IHC may be a helpful screening tool to identify pRCC patients with PHTS.
      Physicians caring for PHTS patients should note the >31-fold increased risk for
      RCC and have a low threshold for investigating possible RCC in patients with
      relevant complaints. Renal ultrasound is not sensitive for detecting pRCC and so
      PHTS patients should have alternate renal imaging (CT or MRI).

PMID- 22381248
TI  - Anatomic site-specific disparities in survival outcomes for penile squamous cell
      carcinoma.
AB  - OBJECTIVE: To identify the predictors of cancer-specific mortality of penile
      squamous cell carcinoma (PSCC) using a population-based database. METHODS: Using
      data from the National Cancer Institute's Surveillance, Epidemiology, and End
      Results registry, we performed a time-to-event analysis to determine which
      clinical parameters were useful in predicting cancer-specific mortality. RESULTS:
      Our cohort consisted of 2515 cases of PSCC diagnosed from 1973 to 2007. The
      patients were divided into 2 groups: primary tumors of the prepuce (n = 722) and
      primary tumors of the glans, body, and overlapping lesions of the skin (n =
      1793). The median follow-up for the cohort was 39 months (range 1-411). Compared
      with tumors of the prepuce, tumors of the body (hazard ratio 1.61, 95% confidence
      interval 1.00-2.60, P = .05) and overlapping tumors of the skin (hazard ratio
      1.79, 95% confidence interval 1.13-2.83, P = .01) had a greater risk of cancer
      specific mortality, even when controlling for age, Surveillance, Epidemiology,
      and End Results stage, and tumor grade. Furthermore, the disease-specific 10-year
      survival rate of those with preputial tumors was 89.4% compared with 78.7% for
      the other 3 groups combined (P < .0001). CONCLUSION: Anatomic site-specific
      disparities for PSCC survival appear to exist. Patients diagnosed with PSCC of
      the prepuce have greater overall long-term disease-specific survival than
      patients with primary tumors elsewhere.

PMID- 22381249
TI  - A 38-year-old woman with multiple renal masses and a history of ovarian cancer.

PMID- 22381250
TI  - Mitochondrial respiratory efficiency is positively correlated with human sperm
      motility.
AB  - OBJECTIVE: To correlate sperm mitochondrial respiratory efficiency with
      variations in sperm motility and with sperm morphologic anomalies. METHODS: Sperm
      mitochondrial respiratory activity was evaluated with a polarographic assay of
      oxygen consumption carried out in hypotonically-treated sperm cells. A possible
      relationship among sperm mitochondrial respiratory efficiency, sperm motility,
      and morphologic anomalies was investigated. RESULTS: Mitochondrial respiratory
      efficiency was positively correlated with sperm motility and negatively
      correlated with the percentage of immotile spermatozoa. Moreover, midpiece
      defects impaired mitochondrial functionality. CONCLUSION: Our data indicate that
      an increase in sperm motility requires a parallel increase in mitochondrial
      respiratory capacity, thereby supporting the fundamental role played by
      mitochondrial oxidative phosphorylation in sperm motility of normozoospermic
      subjects. These results are of physiopathological relevance because they suggest
      that disturbances of sperm mitochondrial function and of energy production could
      be responsible for asthenozoospermia.

PMID- 22381251
TI  - Relationship between mean platelet volume and varicocele: a preliminary study.
AB  - OBJECTIVE: To examine the relationship between the mean platelet volume (MPV) and
      varicocele to clarify the etiopathogenesis of varicocele. METHODS: MPV levels
      were measured in 60 varicocele subjects (group I) and 57 healthy controls (group
      II) from 2009-2010. Ages were similar between the 2 groups. The diagnosis of
      varicocele was based on the findings from both physical examination and color
      Doppler ultrasound. RESULTS: The average patient age at the time of examination
      was 28.12 +/- 6.4 years in group I and 28.10 +/- 5.8 in group II. MPV levels were
      statistically significantly higher in group I than in group II (P < .001).
      Positive correlations were found between MPV and varicocele grade as between MPV
      and diameter of left spermatic vein (P < .05). CONCLUSION: The increase in MPV is
      independent of the disease, and the increase in varicocele grade is associated
      with higher MPV in varicocele patients. On the basis of the importance of the
      vascular component in the pathophysiology of varicocele, we would suggest
      conducting more studies with platelets in varicocele patients.

PMID- 22381252
TI  - Split dorsal dartos flap transposed ventrally as a bed for preputial skin graft
      in primary staged hypospadias repair.
AB  - OBJECTIVE: To describe a modification of the 2-stage repair using a dorsal split
      dartos fascia flap, as a well vascularized bed for the graft in the first
      stage.The 2-stage repair is a commonly used technique in proximal hypospadias or
      in hypospadias with severe chordee, or in cases with urethral plate of poor or
      dubious quality. METHODS: Between 2006 and 2009, 32 patients underwent a staged
      hypospadias repair: 8 (25.0%) midshaft with chordee and/or poor urethral plate,
      14 (43.8%) proximal penile, 7 (21.9%) peno-scrotal, and 3 (9.4%) perineal
      hypospadias. Plication was necessary in 27 (84.4%). All cases received a
      preputial skin graft. Median age at the first stage was 21 months (range 15-26);
      median follow-up was 35 months (range 20-55) and the median time between the 2
      stages was 8 months (range 6-12). RESULTS: Graft take was 100% after the first
      stage. Follow-up after second-stage repair showed 31 of 32 (96.8%) had a
      successful functional outcome (straight erection; good, single urine stream;
      voiding in a standing position) and cosmetic outcome (slitlike meatus positioned
      at the tip of the glans, "normal looking circumcised penis"); one fistula
      occurred. One patient has mild residual ventral curvature. CONCLUSION: Using a
      vascularized dorsal split dartos flap ventrally underneath and laterally of the
      skin graft in the first stage offers the advantages of an excellent graft take
      and the provision of versatile dartos tissue for a waterproofed and secured
      urethroplasty.

PMID- 22381253
TI  - Topically applied semaphorin 3A ointment inhibits scratching behavior and
      improves skin inflammation in NC/Nga mice with atopic dermatitis.
AB  - BACKGROUND: Epidermal hyperinnervation in atopic dermatitis (AD) is activated
      directly by various external stimuli, causing enhanced itching. Nerve density is
      regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve
      elongation factors. OBJECTIVE: To investigate the effects of Sema3A ointment in
      the NC/Nga mouse model of AD. METHODS: An AD-like phenotype was induced by
      repeated application of Dermatophagoides farinae body (Dfb) ointment to the
      dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and
      recombinant Sema3A ointments were applied to the lesional skin once a day for 4
      days. Transepidermal water loss (TEWL) was measured before and after each
      treatment. We also scored the degree of dermatitis and recorded videos to observe
      scratching behavior. Subsequently, we collected skin samples from these mice for
      histological analyses. RESULTS: Topical application of Sema3A, betamethasone and
      tacrolimus ointments significantly inhibited scratching behavior and improved
      dermatitis scores in Dfb-treated mice compared with control mice, whereas
      vaseline and heparinoid had no effects. A significant improvement of TEWL was
      observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced
      the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the
      epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T
      cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared
      with controls. CONCLUSION: Sem3A ointment may have therapeutic efficacy in
      patients with pruritus and dermatitis of AD.

PMID- 22381254
TI  - Lower extremity kinematics in children with and without flexible flatfoot: a
      comparative study.
AB  - BACKGROUND: A high percentage of young children present with flatfeet. Although
      the percentage of those with flatfeet declines with age, about 15% of the
      population maintains a flat arch. A reduction in longitudinal arch height usually
      combines with excessive subtalar joint pronation and may be related to other
      musculoskeletal problems of the lower extremity kinetic chain. The purpose of
      this study is to describe and compare the lower extremity kinematics between
      children with normal arches and those with flexible flatfeet, with the intent of
      providing practical information for decision making when treating children with
      flexible flatfeet. METHODS: Twenty children with flexible flatfeet (years age
      mean (SD), 9.7 (0.9) years) and 10 children with normal arches (yeas age mean
      (SD), 9.6 (1.2) years) were included. Kinematic data (maximum and minimum angles,
      and movement range, velocity, and excursion) of the hip, knee and rearfoot were
      collected during walking using Liberty Electromagnetic Tracking System. Kinematic
      variables were compared between the normal arches and flexible flatfeet groups
      using repeated measures mixed effects ANOVA. RESULTS: Movement patterns at the
      hip, knee and ankle joints were similar between children with flexible flatfeet
      and with normal arches. The results of ANOVA showed no significant main effect or
      interaction in any of the kinematic variables (P >= 0.05). CONCLUSIONS: This
      study identified no kinematic adaptation during walking in children with flexible
      flatfoot. We suggested that future research should take the influence of the mid
      foot and forefoot into consideration when examining lower extremity kinematics in
      children with flexible flatfoot.

PMID- 22381255
TI  - Preventing weight gain through exercise and physical activity in the elderly: a
      systematic review.
AB  - This review examines the role of exercise and physical activity for preventing
      weight gain in older people. A structured search using MeSH-vocabulary and
      Title/Abstract-searches was conducted in PubMed for January 2000 to June 2011,
      identifying weight gain and exercise or physical activity as study topics, and
      aged adults as target group. In study selection, all types of exercise and
      physical activity and any measure of weight change in aged adults (>=65 years) or
      postmenopausal women were considered. N=9 primary studies were identified. All
      were conducted in the US, with one study additionally including samples from
      Canada and the UK. Three studies focused on aged adults, while six concentrated
      specifically on postmenopausal women. Forms of exercise or physical activity
      comprised self-reported exercise history in four studies and low, moderate or
      high intensity exercise interventions in five studies. Four studies combined
      exercise with a hypocaloric diet and included comparison groups receiving either
      diet only, health education, stretching or a delayed intervention (one study
      each). Exercise was associated with weight loss (1.1-6 kg) in all intervention
      studies, all of which studied an overweight sample, and with weight maintenance
      in most observational studies, all of which studied a general population or
      otherwise overweight-unspecific sample. In sum, exercise and physical activity
      can effectively prevent weight gain in older adults and postmenopausal women
      either in terms of weight loss or maintenance. They can preserve lean body mass
      and thus are important for the balance between potentially positive and negative
      effects of weight reduction in later life. In addition, since all intervention
      studies were conducted with an overweight sample, it seems that primordial
      prevention (in terms of preventing the development of risk factors such as excess
      weight in the first place) might be a neglected issue in geriatric and
      postmenopausal prevention.

PMID- 22381256
TI  - Effects of [6]-shogaol on cholinergic signaling in HT22 cells following neuronal
      damage induced by hydrogen peroxide.
AB  - Cholinergic neurons play a major role in memory and attention. The dysfunction
      and death of these neurons, especially in the hippocampus, are thought to
      contribute to the pathophysiology of memory deficits associated with Alzheimer's
      disease (AD). Therefore, studying the cholinergic properties and cell survival
      may help in treating this disease. We investigated the possible effects of [6]
      shogaol on cholinergic signaling in HT22 hippocampal neuronal cells. HT22 cells
      express essential cholinergic markers, including choline acetyltransferase (ChAT)
      and choline transporter (ChTp). HT22 cells treated with H(2)O(2) for 3h showed an
      increase in ROS production (35%). These features were partly recovered by [6]
      shogaol. Treating H(2)O(2)-treated HT22 cells with [6]-shogaol markedly increased
      the expression of ChAT and ChTp, an effect similar to that of brain-derived
      neurotrophic factor (BDNF). Furthermore, K-252a, an inhibitor of the BDNF
      receptor Trk B, attenuated the effects of both [6]-shogaol and BDNF. These data
      suggest that [6]-shogaol protects neurons by increasing ChAT and ChTp expression
      through a BDNF increase and thus may be useful for treating neurodegenerative
      diseases.

PMID- 22381257
TI  - Monascus-fermented metabolite monascin suppresses inflammation via PPAR-gamma
      regulation and JNK inactivation in THP-1 monocytes.
AB  - Fermentation products of the fungus Monascus offer valuable therapeutic benefits
      and have been used extensively for centuries in Asia. The aim of this study is to
      investigate the inhibitory effect of the Monascus-fermented metabolite monascin
      (MS) on the molecular mechanism of ovalbumin (OVA)-induced inflammation in the
      human THP-1 monocyte cell line. We found that 1, 5, and 25 MUM of MS
      significantly attenuated several proinflammatory mediators, including inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression as well as
      nitric oxide (NO) and prostaglandin E(2) (PGE(2)) formation caused by OVA
      stimulation. Further, 5 and 25 MUM of MS significantly reduced the generation of
      tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) at both the
      protein and mRNA levels. MS (5 and 25 MUM) decreased OVA-induced phosphorylation
      of mitogen-activated protein kinase (MAPK) c-Jun NH(2)-terminal kinase (JNK), but
      not that of extracellular signal-regulated kinase (ERK) or p38 kinase. We used
      the peroxisome proliferator activated receptor-gamma (PPAR-gamma) antagonist
      GW9662 to show that MS inhibit JNK phosphorylation through increased expression
      of PPAR-gamma. Thus, the metabolites from Monascus fermentation may serve as a
      dietary source of anti-inflammatory agents.

PMID- 22381258
TI  - The Perception Gap: Recognizing and managing the risks that arise when we get
      risk wrong.
AB  - Many in the academic, science, and business communities are frustrated at how
      people perceive and respond to risk, lamenting that the lay public is sometimes
      more afraid of some threats than the evidence warrants, and less afraid of some
      dangers than the evidence warns. This is often ascribed to the alarmist way the
      news media cover risk-related subjects. That criticism is simplistic and
      unproductive, and ignores or dismisses the large body of research that finds that
      the perception of risk is not, and can never be, perfectly rational. Risk
      perception among members of the public, the media, and members of the academic,
      scientific, and business communities, is ultimately subjective. The gap between
      our fears and the evidence is not simply the product of alarmist media reporting.
      This 'Perception Gap' poses significant risks in and of itself, influencing the
      choices we make as individuals and as a society. The roots of the Perception Gap
      must be understood if we are to recognize the dangers that can arise when we
      sometimes get risk wrong, and in order that we may more wisely manage those risks
      as actively as we manage toxicological or food or other risks with which we are
      more familiar.

PMID- 22381259
TI  - In vitro assays of the antibacterial and antioxidant activity of aqueous leaf
      extracts from different Prunus salicina Lindl. cultivars.
AB  - The growing interest in the substitution of synthetic food antioxidants and
      antimicrobial additives by natural ones has fostered research on vegetable
      sources and on the screening of raw materials, for identifying new antioxidants
      and antimicrobial natural agents. The aim of the present study was to assess
      total phenolic contents and determine polyphenolic composition, related
      antioxidative and antimicrobial properties of plum leaves extracts from six
      cultivars. It was observed that the content of total phenolic compounds was
      cultivar dependent. High antioxidant capacity has been observed and related to
      the relative amounts of polyphenolic compounds with good antioxidant properties.
      The antimicrobial activity was confirmed against Listeria innocua and Escherichia
      coli, and it has found to be related with the high phenolic contents. Our results
      suggest that the use of plum leaf extracts is a feasible alternative as
      antibacterial and antioxidant agents to prevent the deterioration of stored foods
      by bacteria and oxidation.

PMID- 22381260
TI  - In vitro toxicity screening of chemical mixtures using HepG2/C3A cells.
AB  - Traditional toxicological methods that utilize only single pure compounds may not
      accurately predict risks from substances with multiple chemical constituents. A
      complementary approach to conventional methodologies includes in vitro systems
      that assess toxicity of chemical mixtures and identify components that may
      adversely impact biological processes. Compared to animal models, in vitro assays
      are inexpensive, rapid, and reduce and refine related animal testing. We utilized
      HepG2/C3A cells as a hepatotoxicity screening model to evaluate the cytotoxic and
      metabolic effects of three commercially available oil dispersants, Corexit
      EC9500A and EC9527A and ZI-400. The surfactant DOSS, a primary active constituent
      of the Corexit dispersants, was also evaluated. Biologically relevant endpoints
      were measured including cell viability, oxidative stress, and mitochondrial
      activity. Significant increases in cytotoxicity were observed with Corexit
      dispersants (LC(50)~250 ppm), whereas ZI-400 was moderately cytotoxic (LC(50)
      >>400 ppm). Each dispersant caused an accumulation of reactive oxygen species and
      altered mitochondrial activity and other cellular processes. Generally, DOSS made
      notable contributions to the effects of EC9500A and EC9527A, however, they were
      observed at concentrations higher than those used in most consumer products.
      Overall, this system may represent a valuable complementary tool for predicting
      the toxicity of complex mixtures.

PMID- 22381261
TI  - Lymphadenectomy in endometrial cancer: what's the right question?

PMID- 22381262
TI  - Simulation of robotic hysterectomy utilizing the porcine model.
AB  - OBJECTIVE: This article describes the simulation of robotically assisted
      hysterectomy utilizing the porcine model. STUDY DESIGN: Utilizing 3 domestic
      pigs, a technique for robotically assisted hysterectomy was developed. An edited
      video clip of the model was assessed by 6 gynecological surgeons. RESULTS: The
      steps of the operation are described in detail and are shown in a video clip.
      Overall the procedure simulated that done in the human both anatomically and
      surgically. Some of the evaluators rated the identification of the cervicovesical
      junction to be more difficult and division of the paracervical ligaments to be
      relatively easier in the model. CONCLUSION: Reported here is a technique for
      robotically assisted hysterectomy in the domestic pig that may be useful for
      training purposes.

PMID- 22381263
TI  - Longitudinal stent deformation: insights on mechanisms, treatments and outcomes
      from the Food and Drug Administration Manufacturer and User Facility Device
      Experience database.
AB  - AIMS: Longitudinal stent deformation (LSD) is a recently described complication
      of PCI, but mechanisms contributing to its occurrence and associated clinical
      outcomes remain unclear. The FDA Manufacturer and User Facility Device Experience
      (MAUDE) database was searched to identify cases of LSD to gain insight into
      procedural and anatomical factors that predispose to this complication and
      associated clinical outcomes. METHODS AND RESULTS: The MAUDE database is a
      voluntary international electronic reporting system whose aim is to capture major
      adverse events involving medical devices. Using defined search terms, we
      identified 57 unique cases of LSD ranging from 2004-2011. A significant increase
      in the reporting of LSD in the last two years was observed with most reported
      cases in stents based on the Element platform (90%). The lesions in which LSD was
      reported were complex (vessel calcification 26%; tortuosity 25%; long 28%; ostial
      disease 21%) and most frequently occurred following attempts to pass or withdraw
      secondary devices through a previously deployed stent (89% cases where mechanism
      identified). Adverse clinical outcomes including emergent cardiac surgery and
      acute and sub-acute stent thrombosis occurred in eight cases. CONCLUSIONS: LSD
      can occur secondary to a variety of mechanisms; identification and treatment is
      important since adverse incidents such as emergent CABG and stent thrombosis may
      occur. A novel classification system is proposed to facilitate future reporting
      of this complication.

PMID- 22381264
TI  - [Clinical retrospective evaluation of the arthroscopic treatments of the
      triangular fibrocartilage complex of the wrist].
AB  - OBJECTIVES: The aim of this study is the retrospective clinical evaluation of the
      arthroscopic treatments for triangular fibrocartilage complex tears. METHODS:
      Between 2003 and 2010, 76 patients with a traumatic lesion (Palmer type 1) and 25
      patients with a degenerative lesion (Palmer type 2) of the triangular
      fibrocartilage complex underwent wrist arthroscopy. Clinical evaluations were
      based on the Mayo Modified Wrist Score (MMWS), on a compared measurement of the
      grip force and on a measurement of the different ranges of motion. We also made a
      subjective evaluation of the benefit brought by arthroscopy and a retrospective
      evaluation of the pre and postoperative pain. RESULTS: Mean MMWS was 86.3 for
      traumatic lesions and 83 for degenerative lesions. Mean grip force was 84.8
      (Palmer type 1) and 84.2 (Palmer type 2) compared to the controlateral side. Mean
      ranges of flexion-extension, prosupination and radioulnar motions were 135
      degrees , 164 degrees  and 56 degrees  respectively for traumatic lesions and 130
      degrees , 156 degrees  and 54 degrees  respectively for degenerative lesions.
      Ninety-four percent of the operated patients reported an improvement of the
      symptomatology with better results for type 1 (98.7%) compared to type 2 (80%).
      We noted a clear diminution of the postoperative pain compared to the
      preoperative's one with frequently some mild persistent pain however.
      CONCLUSIONS: Arthroscopic treatments of the triangular fibrocartilage complex
      seem to be effective with an improvement of the symptomatology.

PMID- 22381265
TI  - The magnitude of priming effects is not independent of prime awareness. Reply to
      Francken, van Gaal, & de Lange (2011).

PMID- 22381266
TI  - [Uncombable hair syndrome].

PMID- 22381267
TI  - Percutaneous trans-facet screws for supplemental posterior cervical fixation.
AB  - BACKGROUND: Numerous innovative minimally invasive fusion and fixation techniques
      for the thoracolumbar spine have recently been developed. However, less-invasive
      approaches for accessing the posterior cervical spine surgery have been more
      elusive. One promising option for posterior cervical fixation is trans-facet
      screw placement. SURGICAL TECHNIQUE: This method allows for a screw to be
      inserted percutaneously through the articular (zygapophyseal) facet joint. This
      eliminates the need for a connecting rod between segments, which remains a major
      limitation of longer segment minimally invasive lateral mass screw-rod
      constructs. Surgery was successfully performed in three consecutive cases with
      the use of existing small fragment cancellous screws intended for orthopedic
      applications. CONCLUSIONS: In this report we describe an initial clinical
      experience with cervical trans-facet screws, which we found to be a technically
      feasible option in the subaxial cervical spine for truly percutaneous spinal
      fixation. However, until percutaneous bony fusion methods are developed, this
      approach is limited to the fixation application, such as supplementing an
      anterior fusion construct.

PMID- 22381268
TI  - Symptomatic Rathke cleft cyst: clinical features and surgical outcomes.
AB  - OBJECTIVE: To depict the clinical, operative, and histological features of Rathke
      cleft cysts (RCCs) in consideration of therapeutic results and recurrence rates.
      METHODS: This study included 40 patients (29 female; mean age, 41 years) of
      symptomatic RCCs with pathological verification. The mean length of follow-up was
      76 months. The patients were treated by complete cyst evacuation combined with
      partial wall excision (7 via craniotomy and 33 transsphenoidally). All subjects
      were examined neurologically, radiologically, and biochemically to ascertain the
      clinical significance of surgery on endocrine and visual improvement. RESULTS:
      Cysts varied in size from 18 to 43 mm (mean, 19.3 mm); 38 (95.0%) had a
      suprasellar component. Presenting symptoms included headache (75.0%),
      chiasmopathy (45.0%), and endocrine dysfunction (37.5%). On magnetic resonance
      imaging, the signal intensities of the cysts were quite variable, with most
      commonly hyperintensity (75.0%) on T2-weighted and hypointensity (40.0%) on T1
      weighted scans, respectively. Cyst contents were found to be mostly mucoid
      (52.5%) and watery (30.0%). Squamous epithelium was identified in 18 specimens
      (45.0%). Headaches and visual symptoms resolved or improved in 76.7% and 78.6% of
      patients, respectively. Hypothyroidism, hypogonadism, growth hormone deficiency,
      and hypocortisolemia was resolved in 44.4%, 30.0%, 33.3%, and 56.3% of patients,
      respectively. Two patients (5%) had repeat surgery for symptomatic relapse.
      Cerebrospinal fluid leakage (2.5%), new hormone deficit (7.5%), and diabetes
      insipidus (5.0%) were observed after surgery. CONCLUSIONS: When RCCs are
      recognized intraoperatively, the evacuation of their contents and partial cyst
      obliteration generally afford dramatic improvements in a patient's clinical signs
      and symptoms, along with low complications and rate of recurrence.

PMID- 22381269
TI  - Vasospasm after arteriovenous malformation rupture.
AB  - OBJECTIVE: Vasospasm and resultant clinical deterioration caused by delayed
      cerebral ischemia (CD-CDI) are a considerable source of morbidity after
      aneurysmal subarachnoid hemorrhage (SAH). Although they are a relatively common
      cause of spontaneous SAH, AVM rupture and ensuing vasospasm are rarely reported.
      METHODS: We reviewed our own series of 122 patients with AVMs. Seventy-three
      patients sustaining 84 hemorrhages were analyzed. In addition, we performed a
      review of the literature of vasospasm after AVM rupture. RESULTS: Seventy of 84
      hemorrhages (83%) had an intraparenchymal component, 27 (32%) a subarachnoid
      component, and 51 (61%) had an intraventricular component. No patients
      experienced CD-DCI, and of the 84 hemorrhages reported, only one patient
      experienced mild angiographic vasospasm (1.1%). Alternatively, this finding
      represents 1 in 34 cases (2.9%) who underwent definitive angiography between the
      fourth and fifteenth day after the hemorrhage. Nineteen additional cases of
      angiographic vasospasm after AVM rupture are reported in the literature. The mean
      age of these patients was 33 years; there was a 1.25:1 female to male
      predominance in this group. One-half of these patients had an intraparenchymal
      hemorrhage, and only 56% of them had SAH. All patients had intraventricular
      hemorrhage when assessed. The median time to onset of vasospasm was nine days.
      Across four series, the rate of angiographic spasm after SAH from an AVM was 6.3%
      (9/142 cases). CONCLUSIONS: Even in cases of SAH from AVMs, angiographic
      vasospasm after AVM rupture is relatively rare. We thus do not recommend empiric
      delayed angiography to assess for vasospasm in these patients. Nevertheless, it
      does remain a rare possibility and should be considered in those with CD-DCI.

PMID- 22381270
TI  - Venous thromboembolism after thoracic/thoracolumbar spinal fusion.
AB  - OBJECTIVE: Venous thromboembolism (VTE), which includes deep venous thrombosis
      and pulmonary embolism, is a serious and potentially fatal surgical complication.
      The goal of our study was to examine preoperative characteristics, incidence, and
      outcomes of patients with VTE after elective thoracic/thoracolumbar level spine
      fusion. METHODS: We identified 430,081 patients from the Nationwide Inpatient
      Sample database who underwent spinal fusion between 2002 and 2008. Patients
      undergoing thoracic/thoracolumbar level fusion (n = 8617) were found to have the
      greatest concurrent rate of VTE. We then performed multivariate analyses on this
      cohort to identify predictors of and outcomes after VTE in patients undergoing
      thoracic/thoracolumbar level fusion. RESULTS: The overall VTE rate in spinal
      fusion surgery was 0.40% (cervical = 0.22%, thoracic/thoracolumbar = 1.90%,
      lumbar/lumbosacral = 0.49%, re-fusions = 0.64%, and fusions not otherwise
      specified = 0.84%). On multivariate logistic regression analysis of patients
      undergoing spinal fusion at the thoracic/thoracolumbar level, increasing age,
      Medicare insurance coverage (vs. private insurance), urban teaching hospital (vs.
      urban nonteaching hospital), combined anterior/posterior surgical approach (vs.
      posterior-only approach), and the presence of congestive heart failure or weight
      loss (Elixhauser comorbidity groups) were each independently associated with an
      increased odds ratio of VTE complication. VTE after thoracic/thoracolumbar
      surgery was significantly associated with longer hospital stays (16.6 vs. 6.74
      days), increased total hospital costs ($260,208 vs. $115,474), and increased
      mortality (4.33% vs. 0.33%). CONCLUSIONS: Multivariate logistic regression
      analysis reveals age, insurance status, hospital type, combined
      anterior/posterior surgical approach, and the presence of congestive heart
      failure or weight loss to be independently associated with an increased odds
      ratio of VTE complication. This complication is associated with increased
      hospital costs, length of stay, and overall mortality.

PMID- 22381271
TI  - Utility of the CO2 laser in the microsurgical resection of cavernous
      malformations.
AB  - OBJECTIVE: The CO2 laser has a long record of use in neurosurgery. However, its
      utility has been limited by its bulky design and the challenge of using it with
      the operating microscope. With the development of the OmniGuide fiber, a
      technology that delivers the beam through flexible hollow-core photonic bandgap
      mirrors, the laser can now be held and used with greater ease and accuracy.
      METHODS: We retrospectively analyzed a prospectively maintained database to
      assess the utility of the laser in 23 consecutive patients (10 male, 13 female;
      mean age, 40.8 years; range, 9-64 years) with a cavernous malformation treated by
      the senior author (R.F.S.). RESULTS: Four lesions were located in noneloquent
      areas, 13 were in the brain stem, four were in the spinal cord, and two were in
      the thalamus. The usefulness of the laser was rated on a scale of 1 to 5, with 5
      defined as "extremely helpful." The mean utility score was 3.5 +/- 0.94 (range, 2
      5). The laser was judged most useful in creating cortisectomies in eloquent areas
      and in "shrinking" cavernous malformations away from adjacent hemosiderin-stained
      tissue. The laser was ineffective against calcification and in obtaining
      hemostasis. CONCLUSIONS: The CO2 laser is a useful addition to the neurosurgical
      armamentarium for treating lesions in the brainstem, thalamus, and spinal cord.
      Its primary utility lies in its ability to create focused cortisectomies safely
      and to shrink cavernous malformations away from eloquent hemosiderin-stained
      brain.

PMID- 22381272
TI  - Coexistence of extra-axial cavernous malformation and cerebellar developmental
      venous anomaly in the cerebellopontine angle.
AB  - BACKGROUND: The coexistence of cavernous malformations (CMs) and developmental
      venous anomalies (DVAs) in the cerebellopontine angle (CPA) is exceedingly rare.
      To the authors' knowledge, only one case of CPA CM with concurrence of a
      neighboring DVA has been reported to date. CASE DESCRIPTION: The authors
      presented such vascular malformations in a 36-year-old man with progressive CPA
      syndrome during the course of six weeks. Preoperative neuroimaging suggested the
      diagnosis of an extra-axial hemorrhagic lesion in the CPA cistern with a
      cerebellar DVA in the close vicinity. The lesion was totally removed with the DVA
      untouched and was confirmed to be extra-axial in intimate contact with only the
      VII-VIII complex and the draining veins of DVA. Pathology revealed a CM. The
      patient underwent partial improvement in neurological function postoperatively.
      The radiographic follow-up at one year revealed no recurrence. CONCLUSIONS: CMs
      should be considered in the differential diagnosis of any extra-axial hemorrhagic
      mass, especially with a DVA in the proximity. The coexistence of CM and DVA in
      CPA, although maybe just a coincidence, suggests the possibility of a new subtype
      of extra-axial CPA CM secondary to a preexisting DVA. A long-term follow-up is
      justified in discovering the potential mechanism and biology of such uncommon
      vascular malformations.

PMID- 22381273
TI  - Expression and activation of STAT family proteins in cerebral arteriovenous
      malformations.
AB  - OBJECTIVE: Cerebral arteriovenous malformations (AVMs) do not seem to be static
      congenital vascular malformations but rather are dynamically changing
      pathologies. In this work, we investigated the expression and possible activation
      of different signal transducers and activators of transcription (STAT) family
      members in AVM nidus. METHODS: Immunohistochemical analysis was conducted on 25
      AVM specimens from 24 patients using antibodies against STATs 1, 3, 5, and 6 as
      well as their phosphorylated forms. Analysis was also undertaken to determine if
      there is any correlation between STAT activation and different clinical
      parameters of AVM patients. RESULTS: Our studies revealed that both STATs 1 and 3
      were highly expressed in cerebral AVM, mainly in the endothelium of AVM blood
      vessels and perivascular infiltrating inflammatory cells within the nidus. STAT3
      showed the most intense level of expression within the endothelium and
      perivascular infiltrating inflammatory cells. It was intensely expressed in the
      endothelium of 25 (100%) specimens and in the infiltrating inflammatory cells of
      24 (96%) specimens. The expression of the phospho-STATs 1 and 3 was also high in
      the endothelium and perivascular infiltrating inflammatory cells indicating
      activation of STATs 1 and 3 in AVM. We could not find any significant effect of
      hemorrhage or preoperative embolization, or other clinical parameters, on the
      activation of STATs 1 and 3 in cerebral AVMs. CONCLUSION: We obtained evidence
      for significant overexpression and activation of both STATs 1 and 3 in cerebral
      AVM, thus suggesting an important role for these proteins in mediating the
      pathophysiology of cerebral AVM.

PMID- 22381274
TI  - Complications necessitating a return to the operating room following intradural
      spine surgery.
AB  - OBJECTIVE: To determine the incidence of and risk factors for cerebrospinal fluid
      (CSF), wound, and hematoma-related complications following intradural spine
      surgery. BACKGROUND: Complications of intradural spinal surgery requiring a
      return to the operating room lengthen hospital stay and increase cost as well as
      patient risk. Here we present our experience with complications in intradural
      spinal surgery. METHODS: Between 1993 and 2010, a total of 528 pediatric and
      adult patients who underwent biopsy and/or resection of intramedullary or
      extramedullary spinal lesions at Mayo Clinic-Rochester were evaluated. RESULTS:
      The overall complication rate in this series was 4.9%. Complications, such as
      neurologic worsening due to an etiology not able to be treated surgically, or
      medical complications, such as deep venous thrombosis, were not included in this
      study. The overall complication rates that were CSF-related, wound-related,
      hematoma-related, and miscellaneous were 3.0%, 1.1%, 0.6%, and 0.2% respectively.
      Complication rates decreased with age from 15.4% in 0- to 10-year-olds to 4.1% in
      61- to 90-year-olds. Tumors represented the majority of pathology at 90.5%. The
      complication rate for patients who had prior treatment was higher at 6.9%
      compared with 4.7% in those who had no prior treatment (P = 0.5). Intramedullary
      tumors had a complication rate of 7.1% vs. 3.6% for extramedullary tumors (P =
      0.14). Some patients (5.7%) had coexisting intracranial tumors at the time of
      their surgery but none had complications with intradural spine surgery.
      CONCLUSIONS: Complications of intradural spine surgery are most commonly CSF
      related, may decrease with increasing age of the patient, and are higher with
      intramedullary tumors.

PMID- 22381275
TI  - Transplantation of human adipose-derived stem cells in a rabbit model of
      traumatic degeneration of lumbar discs.
AB  - OBJECTIVE: The purpose of the present study is to assess the possibility of disc
      regeneration by treatment with adipose-derived stem cells (ADSCs) in a rabbit
      model of degenerative disc disease, and to evaluate the efficacy of a
      percutaneous technique for constructing a model of degenerative disc disease in
      rabbits. METHODS: The study sample consisted of 20 mature male New Zealand white
      rabbits. Intervertebral discs were injured in each rabbit by a percutaneous
      technique at L2-3, L3-4, and L4-5 under C-arm guidance with a 19-gauge spinal
      needle. Magnetic resonance images (MRI) were checked at 6, 9, 12, and 15 weeks
      after injury to evaluate disc degeneration. Nineteen weeks after injury, ADSCs
      were injected into the L4-5 disc space, with saline injected into the L3-4 disc
      as a control, using a 21-gauge spinal needle. Histologic confirmations of
      degenerated discs were performed at 10 and 18 weeks after injury with safranin O
      and trichrome stains. RESULTS: MRI revealed intervertebral disc degeneration from
      9 weeks after injury, and full degeneration at 15 weeks after injury, when
      compared with uninjured control discs. We confirmed the proliferation of ADSCs at
      the L4-5 level in 10-week rabbits after cell injection. Histologically, the ADSC
      injected discs exhibited elevated extracellular matrix secretion and little
      ossification of damaged cartilage in the nucleus pulposus compared with
      degenerative control discs. CONCLUSIONS: These results suggest that the injection
      of ADSCs into injured lumbar discs could be an effective treatment for
      degenerative disc disease by promoting the cartilage regeneration.

PMID- 22381276
TI  - Is allograft sufficient for posterior atlantoaxial instrumented fusions with
      screw and rod constructs? A structured review of literature.
AB  - OBJECTIVE: Iliac crest autograft remains the gold standard for spinal fusion
      operations. Given risk of donor site morbidity, many centers utilize allograft.
      We reviewed published series of C1-2 posterolateral instrumented fusions with
      allograft and autograft. METHODS: Online databases were searched for English
      language articles reporting quantifiable outcome data published between 1994 and
      2011 of posterior atlantoaxial instrumented arthrodesis with C1 and C2 screws.
      Thirteen studies describing 652 patients having autograft and seven studies
      describing 60 patients having allograft serve as the basis of this report.
      RESULTS: All studies were retrospective case series (Class III evidence). There
      were no differences in complications or mortality between the groups. There were
      trends toward shorter operative times and less blood loss using allograft. A
      higher proportion of patients in the allograft group underwent sacrifice of the
      C2 nerve root and decortication and packing of the C1-2 joints (P<0.0001). There
      was no significant difference in the proportion of surviving patients who
      achieved solid fusion in the autograft (642 of 644 [99.7%]) and allograft
      patients (59 of 59 [100%]; P = 1.0). CONCLUSIONS: This review is limited by the
      retrospective data and inconsistent methodology of fusion determination used in
      most studies. Modern instrumentation and proper surgical techniques result in
      high rates of successful C1-2 arthrodesis. The use of allograft is a treatment
      option (Class III evidence) during posterior C1-2 instrumentation and fusion
      operations. Randomized, controlled trials using standardized radiographic
      assessments are needed across spinal arthrodesis studies to better determine the
      prevalence of radiographic fusion and establish technique superiority.

PMID- 22381277
TI  - Laminectomy and extension of instrumented fusion improves 2-year pain,
      disability, and quality of life in patients with adjacent segment disease:
      defining the long-term effectiveness of surgery.
AB  - OBJECTIVE: Adjacent segment disease (ASD) may occur as a long-term consequence of
      spinal fusion and is associated with significant back and leg pain. Surgical
      management of symptomatic ASD consists of neural decompression and extension of
      fusion. However, conflicting results have been reported with respect to the long
      term clinical effectiveness of revision surgery in this setting. We set out to
      comprehensively assess the long-term clinical outcome after revision surgery and
      determine its effectiveness in the treatment of adjacent segment disease.
      METHODS: Fifty patients undergoing revision surgery for ASD-associated back and
      leg pain were included in this study. Baseline and 2-year Visual Analog Scale
      Back Pain (VAS-BP), Visual Analog Scale-Leg Pain (VAS-LP), Oswestry Disability
      Index, physical and mental quality of life (Short Form-12 [SF-12] physical and
      mental component score [PCS and MCS]) and health-state utility (EuroQol [EQ-5D])
      were assessed. RESULTS: A sustained improvement in VAS-BP (8.72 +/- 1.85 vs. 3.92
      +/- 2.84, P = 0.001), VAS-LP (6.30 +/- 3.90 vs. 3.02 +/- 3.03, P = 0.001),
      Oswestry Disability Index (28.72 +/- 9.64 vs. 18.48 +/- 11.31, P = 0.001), SF-12
      PCS (26.89 +/- 8.85 vs. 35.58 +/- 11.97, P = 0.001) and SF-12 MCS (44.66 +/-
      12.85 vs. 53.16 +/- 9.46, P = 0.001) was observed 2 years after revision surgery,
      with a cumulative mean 2-year gain of 0.76 quality-adjusted life-years (EQ-5D).
      Median (interquartile range) time to narcotic independence and return to work was
      1.7 (1.0-8.0) months and 2.0 (1.0-4.75) months, respectively. CONCLUSIONS:
      Patients undergoing decompression and extension of fusion for adjacent segment
      disease-associated back and leg pain reported long-term improvement in pain,
      disability, and both physical and mental quality of life, suggesting that
      revision surgery is a highly effective treatment strategy in this patient
      population.

PMID- 22381278
TI  - Cervical spinal brucellosis with epidural abscess causing neurologic deficit with
      negative serologic tests.
AB  - BACKGROUND: Here we present a case of cervical spinal epidural abscess causing
      neurologic deficits despite negative serologic tests. CASE DESCRIPTION: Unlike a
      previously reported case, blood cultures and serologic tests were negative for
      this 50-year-old male with cervical brucellar spondylodiscitis and neurologic
      deficits. The diagnosis was made based on magnetic resonance imaging (MRI)
      findings and tissue culture. We drained the epidural abscess, performed anterior
      cervical discectomy fusion with an iliac strut bone graft, and administered
      antimicrobial therapy (gentamicin and doxycycline). At the 1-year follow-up
      visit, a C-spine lateral plain radiograph revealed solid fusion achieved by
      autogenous strut bone grafting at C4-C5 and C5-C6, and a T2-weighted image showed
      that epidural abscess and granulation tissue causing spinal cord compression were
      absent. In addition, the patient had recovered from all of the neurologic
      deficits with the exception of voiding difficulty. CONCLUSION: It is important
      for clinicians to consider brucellar cervical spondylodiscitis when an epidural
      abscess is identified in a patient with a history of potential exposure. We
      recommend both blood and tissue cultures for diagnosis when serologic tests are
      negative.

PMID- 22381279
TI  - Decompressive hemicraniectomy, strokectomy, or both in the treatment of malignant
      middle cerebral artery syndrome.
AB  - OBJECTIVE: We sought to evaluate the impact of a craniotomy for strokectomy (CS)
      with bone replacement, decompressive hemicraniectomy (DHC), or DHC with a
      strokectomy (DHC+S) on outcome after malignant supratentorial infarction.
      METHODS: We conducted a retrospective cohort study of cases of malignant
      supratentorial infarction treated by CS (n = 18), DHC (n = 17), or DHC+S (n = 33)
      at our institution from 2002 to 2008. End points included functional outcome
      measured by the modified Rankin Scale and incidence of mortality at 1 year.
      RESULTS: Mean age, gender, side, vessel, and time from ictus to surgery were not
      statistically different between treatment groups. Stroke volume was significantly
      higher in the CS group. Operative time and blood loss were significantly higher
      in the DHC+S group. At 1 year, the median modified Rankin Scale score was 4 and
      overall survival was 71%. Functional outcomes and mortality for both the CS and
      DHC+S groups were not significantly different from the DHC group (P = 0.24).
      After adjusting for patient age, stroke volume, and time to surgery, there was no
      significant difference in outcome. CONCLUSION: In patients with malignant
      supratentorial infarction, a strokectomy alone may be equivalent to a
      decompressive hemicraniectomy with or without brain resection.

PMID- 22381280
TI  - Occipitocervical fusion in an infant with atlantooccipital dislocation.
AB  - BACKGROUND: For children who survive traumatic atlantooccipital dislocation
      (AOD), early surgical stabilization and arthrodesis of the occipitoatlantoaxial
      complex is typically performed. Because of the unique and crowded anatomy of the
      occipitocervical junction, the creation of a fusion construct that is both safe
      and biomechanically sound is extremely challenging, especially in infants. We
      present a technical report of a patient with infantile type I AOD with gross
      instability, who underwent surgical stabilization consisting of occiput to C2
      arthrodesis using autologous rib, augmented with bone morphogenic protein 2 (BMP
      2), Mersilene suture, and Ethibond suture as "cross-connectors." CASE
      DESCRIPTION: The patient is a 12-month-old female infant who was involved in a
      high-speed motor vehicle accident and sustained a type I AOD. Definitive surgical
      stabilization consisting of arthrodesis from the occiput to C2 using autologous
      rib augmented with BMP-2, Mersilene suture, and Ethibond suture as cross
      connectors was performed. There were no intraoperative complications. A follow-up
      cervical spine computed tomography obtained 12 weeks postoperatively demonstrated
      excellent occipitocervical alignment, with evidence of modest bony fusion from
      the occiput to C2. Neurologic examination demonstrated modest, but progressive,
      improvement, with partial resolution of bilateral sixth nerve palsies, and
      improvement in upper- and lower-extremity muscle strength and tone. CONCLUSION:
      Significant surgical challenges exist regarding occipitocervical fusion in
      infants with AOD and gross instability. This case report illustrates the
      successful application of BMP-2-augmented occipitocervical fusion using
      autologous rib, in combination with Mersilene and Ethibond suture, in the
      treatment of an infant with type I AOD with gross instability.

PMID- 22381281
TI  - Nerves are not made to be cut.

PMID- 22381282
TI  - Intracerebral hemorrhage: a transition phase toward better prognosis.

PMID- 22381283
TI  - Revascularization and cerebral hyperperfusion: we know what but not why.

PMID- 22381284
TI  - Spinal arthroplasty: differences between the cervical and lumbar spine.

PMID- 22381285
TI  - Facial nerve monitoring in posterior fossa surgery.

PMID- 22381286
TI  - Literature review of various treatment plans and outcomes for brain metastases
      from colorectal cancer.

PMID- 22381287
TI  - Techniques of atlantoaxial fixation and the resection of C2 nerve root.

PMID- 22381288
TI  - Skull base cholesterol granulomas: the endoscopic endonasal perspective.

PMID- 22381289
TI  - Cerebral hyperperfusion after neurovascular reconstruction surgery: what have we
      learned?

PMID- 22381290
TI  - Craniotomy for acute subdural hematoma in the elderly: not as bad as you thought.

PMID- 22381291
TI  - Facial nerve monitoring during surgery of cerebellopontine angle and skull base
      surgery.

PMID- 22381292
TI  - Intramedullary astrocytomas surgery in adult patients: the rationale for cautious
      surgery.

PMID- 22381293
TI  - Concussions in soccer: use your head--but not as a weapon.

PMID- 22381294
TI  - Free-living amoebas: is it safe to go in the water?

PMID- 22381295
TI  - Dural repair after craniotomy and the use of dural substitutes and dural
      sealants.

PMID- 22381296
TI  - Cervical spine reconstruction in cases of compromised bone quality.

PMID- 22381297
TI  - Neurocognitive changes in pituitary adenoma patients after fractionated external
      beam radiotherapy versus gamma knife radiosurgery.

PMID- 22381298
TI  - Occipitocervical fusion in elderly patients: lessons learned.

PMID- 22381299
TI  - Transcervical double mandibular osteotomy approach to the infratemporal fossa.
AB  - BACKGROUND: In this study, we propose an alternative to the traditional
      transmandibular lower lip and chin splitting approach for exposing high
      infratemporal fossa and parapharyngeal space lesions involving the carotid canal
      and jugular foramen. METHODS: We present 2 cases of high skull base tumors
      removed transcervically with anterior and posterior segmental mandibulotomies
      preserving the mental nerve without the use of a lip or chin incision. RESULTS:
      Making the posterior osteotomy in an inverted L configuration is necessary so
      that the coronoid process does not prevent rotation of the mandible out of the
      visual field. Both patients had complete tumor resection with access to the
      carotid canal and jugular foramen and functional preservation of the mental nerve
      and marginal branch of the facial nerve. Neither patient had malocclusion or
      other dental complications from the approach. CONCLUSIONS: This novel technique
      is useful for providing excellent access to high infratemporal fossa or
      parapharyngeal space tumors. It avoids the traditional chin or lip incision and
      preserves the mental and facial nerves and is a useful procedure in the
      armamentarium of skull base/cerebrovascular neurosurgeons.

PMID- 22381300
TI  - Cauda equina syndrome associated with longstanding instrumented spinal fusion.
AB  - BACKGROUND: This study sought to describe a patient with a slowly progressive
      cauda equina syndrome (CES) who had imaging findings of the CES that occurs as a
      rare complication of ankylosing spondylitis (AS), but whose spinal fusion was due
      to thoracolumbosacral instrumentation, not spondyloarthropathy. METHODS: A 53
      year-old woman presented with a 5-year history of slowly progressive CES
      affecting sensory and sphincter more than motor function many years after
      sequential instrumented fusions of her thoracic and then lumbosacral spine.
      Imaging studies showed enlargement of the caudal sac and dorsal arachnoid
      diverticula eroding into posterior elements of the lumbar spine similar to
      findings reported in patients with CES in longstanding AS. Despite extensive
      evaluation, no other cause for her CES was found. We postulate that our patient's
      CES is on the same pathophysiologic basis as that proposed for patients with
      longstanding AS (fibrosis of peridural tissues with increase in transmitted
      cerebrospinal fluid pulse pressure). Because of reports that patients with CES
      due to longstanding AS are helped by placement of a lumboperitoneal shunt, our
      patient underwent this procedure. RESULTS: Seventeen months postoperatively, the
      patient's symptoms and neurologic examination are unchanged, and her previous
      slow progression has been halted. CONCLUSIONS: This case strongly suggests that
      extensive surgical thoracolumbosacral fusion can, rarely and after many years, be
      associated with lumbosacral nerve root damage and a slowly progressive CES that
      is similar to that seen in patients with spinal fusion due to longstanding AS.

PMID- 22381301
TI  - Reoperation after failed deep brain stimulation for essential tremor.
AB  - OBJECTIVE: To evaluate the effects of reoperation with deep brain stimulation
      (DBS) in the caudal zona incerta (cZi) in patients with failed DBS in the ventral
      intermediate (Vim) nucleus of the thalamus for essential tremor. METHODS: The
      results of reoperation with cZi DBS in five patients with failed Vim DBS were
      retrospectively analyzed. RESULTS: Two patients had early failure of Vim DBS, and
      three after several years of good effect. The mean deviation from the atlas Vim
      target point was 1.4 mm. Before the reoperation Vim DBS improved hand function
      and tremor in the treated hand at 25 %, whereas cZi DBS achieved an improvement
      of 57%. Although cZi was more efficient than Vim DBS, also in the patients with
      late failure of Vim DBS, they still exhibited a considerable residual tremor on
      cZi DBS. CONCLUSIONS: The effect on tremor was, in this small sample population,
      improved by implanting an electrode in the cZi. The effect was modest in those
      patients suffering a deterioration years after the initial operation.

PMID- 22381302
TI  - Intraorbital abducens nerve schwannoma.
AB  - BACKGROUND: Schwannomas of the abducens nerve are extremely rare tumors. The
      tumor may be located within the cavernous sinus or more often at the prepontine
      region. However, literature research has identified only one case of isolated
      schwannoma of the orbit, arising from the terminal branches of the abducens nerve
      to the lateral rectus muscle. This is only the second report of an abducens nerve
      schwannoma located entirely intraconal. CASE DESCRIPTION: We report a case of an
      intraorbital abducens nerve schwannoma in a 42-year-old man with no signs of
      neurofibromatosis. The lesion resulted in progressive diplopia and focal abducens
      palsy. The clinical, radiologic, and pathologic features are presented. RESULTS:
      We point the particular aspects and discuss the possible treatments and
      approaches to preserve nerve function. CONCLUSIONS: Being a benign lesion, one of
      the goals has always been total removal. The knowledge of the correct anatomic
      features made us believe that the VI nerve function could be preserved. Our case
      is the first example of a total removal with eye abduction preserved. Because of
      that, we believe that it is reasonable to aim for these goals in future cases.

PMID- 22381303
TI  - A multicenter, single-blind, prospective randomized trial to evaluate the safety
      of a polyethylene glycol hydrogel (Duraseal Dural Sealant System) as a dural
      sealant in cranial surgery.
AB  - OBJECTIVE: Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is
      a significant cause of morbidity due to poor wound healing and infection,
      meningitis, and pseudomeningocele formation. Many common dural closure
      techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and
      fibrin glues, are used to achieve watertight closure, although none are US Food
      and Drug Administration approved for this use. DuraSeal Dural Sealant System is a
      polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug
      Administration for obtaining watertight dural closure when applied after standard
      dural suturing. This multicenter, prospective randomized study further evaluated
      the safety of a PEG hydrogel compared with common dural sealing techniques.
      METHODS: A total of 237 patients undergoing elective cranial surgery at 17
      institutions were randomized to dural closure augmented with the PEG hydrogel or
      a control "standard of care" dural sealing technique after Valsalva maneuver
      demonstrated an intraoperative nonwatertight dural closure. Data were collected
      on complications resulting in unplanned postoperative interventions or
      reoperations, surgical site infections, CSF leaks, and other neurological
      complications within 30 days. Surgeons also provided data on the ease of use of
      the dural sealing techniques, as well as preparation and application times.
      RESULTS: The incidences of neurosurgical complications, surgical site infections,
      and CSF leaks were similar between treatment and control groups, with no
      statistically significant difference between the measures. In the PEG hydrogel
      group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7),
      the incidence of surgical site infections was 1.7% (n = 2), and the incidence of
      CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of
      neurosurgical complications was 7.7% (n = 9), the incidence of surgical site
      infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2).
      Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel
      group compared with 66.4% of controls (P < 0.001). The dural augmentation was
      applied in less than 1 minute in 85.7% of the PEG hydrogel group compared with
      66.4% of the control group (P < 0.001). CONCLUSIONS: The PEG hydrogel dural
      sealant used in this study has a similar safety profile to commonly used dural
      sealing techniques when used as dural closure augmentation in cranial surgery.
      The PEG hydrogel dural sealant demonstrated faster preparation and application
      times than other commonly used dural sealing techniques.

PMID- 22381304
TI  - Thoracic nerve root hemangioblastoma: a rare cause of posterior mediastinal mass.
AB  - BACKGROUND: Hemangioblastomas are benign tumors that occur sporadically or as
      part of von Hippel-Lindau disease. Occasionally, they have an extramedullary
      location along the nerve roots and, rarely, are purely extradural. CASE
      DESCRIPTION: We report a rare case of a completely extradural large
      hemangioblastoma in a 32-year-old man presenting with radiculopathy and a
      posterior mediastinal mass. Screening revealed a similar tumor in the right
      cerebellar hemisphere. The patient underwent a right paramedian suboccipital
      craniotomy and total excision of the cerebellar tumor, followed by a left lateral
      thoracotomy and complete excision of the mediastinal lesion. The patient had an
      uneventful recovery. CONCLUSIONS: Hemangioblastomas should be considered in the
      diagnosis of posterior mediastinal tumors in the presence of typical imaging
      features or with associated intra-axial tumors, so as to plan preoperative
      angiography and embolization.

PMID- 22381305
TI  - Survival and treatment patterns of glioblastoma in the elderly: a population
      based study.
AB  - BACKGROUND: As the older segment of the population grows faster than any other
      age group, the number of elderly diagnosed with glioblastoma is expected to
      increase. The aim of this study was to explore survival and the treatment
      provided to elderly patients diagnosed with glioblastoma in a population-based
      setting. We further studied whether increased treatment aggressiveness may have
      contributed to a clinically important survival benefit in the elderly population.
      METHODS: From the Norwegian Cancer Registry, we included 2882 patients who were
      diagnosed with glioblastoma between 1988 and 2008. RESULTS: The proportion of
      patients >=66 years was 42.5% (n = 1224), and 15.9% of patients (n = 459) were
      >=75 years at diagnosis. Treatment patterns varied significantly between age
      groups (P < 0.001). Elderly patients (66 years) were less likely to receive
      multimodal treatment with resection combined with radiotherapy and/or
      chemotherapy. Elderly patients were more likely to receive a diagnosis of
      glioblastoma without histopathologic verification (P < 0.001). Among patients
      receiving multimodal treatment with surgical resection, radiotherapy, and
      chemotherapy, shorter survival was seen in the elderly (P < 0.001). Belonging to
      the age group >=75 years was the strongest predictor of decreased survival (P <
      0.001), thus seemingly of higher prognostic impact than the patterns of care.
      Increasing age, no tumor resection, no radiotherapy, and no chemotherapy were
      identified as independent predictors of reduced survival. There was a
      statistically significant, albeit debatable, clinically relevant survival
      advantage for the oldest patients (>=75 years) diagnosed in the last 5 years of
      the study. CONCLUSIONS: Advancing age remains a very strong and independent
      negative prognostic factor in glioblastoma. Although there has been an increase
      in the aggressiveness of treatment provided to elderly with glioblastoma, the
      gain for the oldest age group seems at best very modest. The prognosis of the
      oldest age group remains very poor, despite multimodal treatment.

PMID- 22381306
TI  - The philosopher's swoon--the concussion of Michel de Montaigne: a historical
      vignette.
AB  - The French philosopher Michel Eyquem de Montaigne (1533-1592) sustained a
      transient loss of consciousness due to a head injury. Montaigne described his
      concussion as a "swoon," with astutely illustrative details of the symptoms he
      experienced, including brief loss of consciousness, with apparent (temporary)
      confusion, and post-traumatic amnesia. His vivid portrayal of the recovery period
      lends understanding of the process of conscious awakening after his near-death
      experience. Thanks to his power of introspection and literary talent we may gain
      insight into the feelings and perceptions of some patients during their recovery
      from concussion.

PMID- 22381307
TI  - Staged surgical treatment for symptomatic vertebrobasilar artery stenosis:
      combined treatment with endovascular angioplasty and bypass surgery.
AB  - OBJECTIVE: Because the early risk of stroke recurrence in patients with posterior
      circulation infarctions is high, patients with vertebrobasilar events require
      active preventive treatment. Previous reports have described the use of balloon
      angioplasty and stenting or surgical revascularization to the vertebrobasilar
      artery area. To compensate for the disadvantages of these techniques, we combined
      endovascular and surgical treatments in a patient with symptomatic
      vertebrobasilar artery stenosis. METHODS: After endovascular surgery, we
      continued medical therapy to stabilize the blood flow in the posterior
      circulation. Superficial temporal artery-superior cerebellar artery bypass was
      planned for the chronic stage (~1-2 months). RESULTS: Three cases (2 vertebral
      artery stenosis, 1 basilar artery stenosis) presented with recurrent transient
      ischemic attacks or deteriorating symptoms under intensive medical treatment. We
      conducted staged therapy using balloon angioplasty followed by superficial
      temporal artery-superior cerebellar artery bypass. All patients were symptom-free
      after treatment with the combined therapy. CONCLUSIONS: Our staged therapy may be
      an effective treatment for symptomatic vertebrobasilar artery stenosis.

PMID- 22381308
TI  - The values of thin sections and three-dimensional reconstruction in the sellar
      region.
AB  - OBJECTIVE: The computerized freezing milling technique is derived from the
      virtual human project. It has been widely used in three-dimensional (3D)
      reconstruction of the human body and organs. With this technique, the study was
      undertaken to explore the 3D features and adjacent anatomic relationships of the
      sellar region for skull base surgery. METHODS: Continuous thin sections on the
      coronary plane were performed with the computerized freezing milling technique
      using a human head specimen. The related structures were described in six
      sections. After segmenting, labeling, and extracting in serial sections, the 3D
      reconstruction of the sellar region was finished with Amira 4.1 software.
      RESULTS: A total of 390 thin coronary sections were obtained. In six sections,
      the anatomic relationships of the pituitary gland, carotid artery, sphenoid
      sinus, and nerves are displayed. Three-dimensional images of the sellar region
      are video films that continuously and dynamically display anatomic structures in
      3D space at different velocities. It can show that the cavernous segment of the
      internal carotid artery is located anterolateral to the sphenoid sinus and
      lateral to the pituitary gland. The optic nerve protrudes into the superolateral
      portion of the sphenoid sinus. CONCLUSIONS: The combination of coronary sectional
      anatomy and 3D reconstruction can display the anatomic characteristics of the
      sellar region. The 3D models are video films that continuously and dynamically
      display anatomic structures in 3D space at different velocities.

PMID- 22381309
TI  - Risk profile of patients with poor-grade aneurysmal subarachnoid hemorrhage using
      early perfusion computed tomography.
AB  - OBJECTIVE: To determine whether perfusion computed tomography (CT) is useful for
      identifying patients with poor-grade subarachnoid hemorrhage (SAH) with
      reversible etiologies and whether early obliteration in patients with poor-grade
      aneurysmal SAH leads to favorable outcomes. METHODS: Patients with new-onset
      aneurysmal SAH in World Federation of Neurological Surgeons (WFNS) grade IV or V
      neurologic condition who had perfusion CT performed at admission were eligible
      for the study. The study retrospectively enrolled 38 patients seen between
      January 2007 and July 2009. The decision to perform an early obliteration was
      made by the family after a discussion with the neurosurgeons, neurointensivists,
      and interventional radiologists. The functional outcomes were correlated with the
      Glasgow Outcome Scale (GOS) at 6 months, and quantitative perfusion CT data were
      collected. RESULTS: This study included 10 (26%) grade IV and 28 (74%) grade V
      patients. Favorable outcomes occurred in 19 (50%) patients, and 11 (29%) patients
      died. After a multivariate logistic regression analysis of the parameters, older
      age (odds ratio 1.104, P = 0.0317), bilateral prolonged mean transient time (MTT)
      at the thalami (odds ratio 4.155, P = 0.0362), and early obliteration (odds ratio
      0.098, P = 0.003) were predictive of poor outcome. CONCLUSIONS: Early bilateral
      prolonged MTT at the thalami and old age are associated with a poor outcome.
      Early obliteration benefits a significant portion of SAH patients.

PMID- 22381310
TI  - Visual complications after stent-assisted endovascular embolization of
      paraophthalmic and suprasellar variant superior hypophyseal aneurysms: the Duke
      Cerebrovascular Center experience in 57 patients.
AB  - OBJECTIVE: To review retrospectively experience with stent-assisted coiling of
      ophthalmic segment internal carotid artery (ICA) aneurysms to report outcome data
      and identify the rate of associated visual complications. METHODS: The Duke
      endovascular database was retrospectively reviewed to identify all ICA aneurysms
      treated with stent-assisted embolization between November 2002 and October 2009.
      Only aneurysms arising from the ophthalmic segment of the ICA and originating
      from the paraophthalmic or suprasellar variant superior hypophyseal artery were
      included. These aneurysms have the potential to create visual disturbances
      related to mass effect on the optic nerve or chiasm or to disrupt the ophthalmic
      artery. Chart review was performed to obtain clinical information, immediate
      incidence, and follow-up of aneurysm remnants and any visual complications.
      RESULTS: There were 63 aneurysms (48 paraophthalmic and 15 suprasellar variant
      superior hypophyseal) identified in 57 patients. The ophthalmic artery was
      preserved in all but two (3.5%) cases, neither of which resulted in visual
      deficits. One (1.8%) patient experienced transient acute visual disturbances, and
      two (3.5%) patients had delayed, persistent deficits. CONCLUSIONS: Stent-assisted
      embolization of ophthalmic segment ICA aneurysms is technically achievable and in
      our series did not appear to result in increased visual complications compared
      with coil embolization alone or surgical treatment.

PMID- 22381311
TI  - Vertebral artery loop--a cause of cervical radiculopathy.
AB  - OBJECTIVE: To report a case of cervical radiculopathy caused by an anomalous
      vertebral artery (VA) and illustrate the efficacy of microvascular decompression
      by the anterolateral approach. METHODS: A 50-year-old woman was referred because
      of an 8-year history of progressive left C6 radiculopathy refractory to other
      forms of treatment, including C5-6 anterior cervical discectomy. Clinical and
      radiologic evaluation showed an abnormally tortuous loop of V2 causing direct
      neurovascular compression. RESULTS: A left cervical anterolateral approach was
      used to expose the anomalous loop. After a generous bony decompression, the loop
      was identified, and the artery was mobilized and ultimately separated from the C6
      nerve root removing the direct pulsatile compression. CONCLUSIONS: Cervical root
      compression by an aberrant or anomalous extracranial VA is a rare cause of
      radiculopathy. The best management of such lesions is the anterolateral approach
      with bony and direct microvascular decompression.

PMID- 22381312
TI  - Predicting outcome after arteriovenous malformation-associated intracerebral
      hemorrhage with the original ICH score.
AB  - OBJECTIVE: To evaluate the predictive ability of the original ICH Score (oICH) in
      a large independent cohort of patients with arteriovenous malformation-associated
      intracerebral hemorrhage (AVM-ICH), an important cause of intracerebral
      hemorrhage (ICH) that is associated with significantly different epidemiology,
      clinical course, and outcome compared with primary ICH. METHODS: During the
      period 1997-2009, 91 patients were admitted to Columbia Medical Center with acute
      AVM-ICH. Demographic and admission clinical and radiographic variables were
      obtained for 84 patients through retrospective chart review. Admission oICH and
      Spetzler-Martin grading scale (SMGS) were calculated. Outcome was assessed at 3
      months using the modified Rankin Scale (mRS). Maximum Youden Indices were used to
      identify cutoffs for age and ICH volume that are associated with optimal
      predictive accuracy for an unfavorable outcome (mRS >= 3). Receiver operating
      characteristic (ROC) analysis was used to evaluate the predictive performance of
      oICH, and oICH with new age and ICH cutoff points (new AVM-ICH score based on
      original ICH Score [AVM-oICH]). RESULTS: The mean age was 35 years +/- 14, and
      mean ICH volume was 22 mL +/- 20. At 3-month follow-up, 3 (4%) patients were
      dead, and 15 (18%) had an unfavorable outcome. Two of the patients who died had
      oICH of 3, and one had oICH of 5. ICH volume of 37 mL and age of 41 years were
      identified as optimal cutoffs for predicting an unfavorable outcome. oICH and AVM
      oICH showed good predictive accuracies with area under the curve of 0.914 and
      0.891 (P = 0.422). AVM-oICH and oICH had similarly high sensitivities (0.889 and
      0.944; P = 1.00), but the former had significantly greater specificity (0.879 vs.
      0.682; P < 0.001). CONCLUSIONS: oICH is a valid clinical grading scale with high
      predictive accuracy for functional outcome after AVM-ICH. It is unclear whether
      the score is appropriate for risk stratification with regard to mortality because
      of the low risk of death associated with AVM-ICH. Simple adjustments of the age
      and ICH volume cutoff points improve performance of the score and reduce the
      probability of overestimating a patient's risk of an unfavorable outcome after
      AVM-ICH.

PMID- 22381313
TI  - Inclusion of asymptomatic degenerative discs in a two-level anterior cervical
      discectomy and fusion: a decision analysis.
AB  - OBJECTIVE: To perform a decision analysis model to compare single-level fusion
      versus two-level fusion in patients with an asymptomatic disc adjacent to a
      symptomatic disc. METHODS: Probabilities and utilities of alternative outcomes in
      the decision tree were assigned based on systematic review of the literature and
      expert opinion. Rollback analysis determined the optimal treatment. Sensitivity
      analyses and Monte Carlo simulations were performed to identify effects of
      varying model parameters. RESULTS: Rollback analysis provided expected values of
      0.92 versus 0.84 in favor of observation as the optimal decision. Sensitivity
      analysis identified the probability of developing adjacent segment disease (ASD)
      and the likelihood of surgery given a diagnosis of ASD as the most critical
      parameters influencing the decision. Observation was the preferred strategy at
      all values of probability of ASD < 100%. At a probability of ASD of 100%, fusion
      was the preferred strategy only when the probability of surgery for ASD was >=
      66% or the utility assigned to successful nonoperative management was <= 0.84.
      CONCLUSIONS: Observation was the preferred strategy for management of
      asymptomatic adjacent degenerative discs (AADDs) given the probabilities and
      utilities used in the decision analysis model. The study was limited by
      unavailability of precise estimates of the probability of development of ASD and
      the probability of surgery after diagnosis of ASD, the most critical factors
      influencing the decision. However, the conclusions were robust given wide ranges
      used for these parameters in the sensitivity analysis.

PMID- 22381314
TI  - Monitoring techniques for prevention of procedure-related ischemic damage in
      aneurysm surgery.
AB  - OBJECTIVE: To describe the application of intraoperative monitoring techniques
      during aneurysm surgery and to discuss the advantages and limitations of these
      techniques in prevention of postoperative neurologic deficits. METHODS: Articles
      found in the literature through PubMed for the time frame 1980-2011 and the
      authors' personal files were reviewed. RESULTS: Various techniques for detection
      of vascular insufficiency are available, including direct methods to measure
      cerebral blood flow and indirect methods to evaluate the integrity of neurologic
      pathways. CONCLUSIONS: The choice of monitoring modality should be governed by
      the vessel and by the vascular territory most at risk during the planned
      procedure with proper awareness of the potential limits related to each
      technique. Aneurysm surgery monitoring should help to address issues of
      continuity and provide a morphologic and functional assessment. Although the use
      of monitoring devices is still not routine in aneurysm surgery and no standards
      have been established, combining different monitoring techniques is crucial to
      optimize aneurysm surgery and avoid or minimize complications.

PMID- 22381315
TI  - Success of endoscopic third ventriculostomy: what does really matter?

PMID- 22381316
TI  - Intraoperative magnetic resonance imaging, neuronavigation, and the transoral
      approach: considerations in adopting novel technologies to a standard surgical
      approach.

PMID- 22381317
TI  - Using the radiobiology of radioresistance and radiosurgery to rethink treatment
      approaches for the treatment of central nervous system metastases.

PMID- 22381318
TI  - Susceptibility-weighted imaging at ultra-high field (7 T) in the evaluation of
      brain tumors.

PMID- 22381319
TI  - Impact of antihelminthic treatment in neurosurgical patients with symptomatic
      neurocysticercosis.

PMID- 22381320
TI  - Neuronavigation in spinal surgery.

PMID- 22381321
TI  - The paradigm of skull base meningiomas: what is optimal?

PMID- 22381322
TI  - Risk factors for three phases of 12-month mortality in a defined population after
      subarachnoid hemorrhage.

PMID- 22381323
TI  - Cognitive changes after treatment: clipping versus coiling.

PMID- 22381324
TI  - What have I learned from my neurosurgical "great-grandfather".

PMID- 22381325
TI  - Surgery for giant acoustic neuroma: total excision at what cost.

PMID- 22381326
TI  - Readability of patient education materials.

PMID- 22381327
TI  - Giant intracranial tumors: a neurosurgical challenge.

PMID- 22381328
TI  - Pituicytomas, a perspective.

PMID- 22381329
TI  - What is an acceptable risk?

PMID- 22381330
TI  - Instrumentation in neurosurgery: nurturing the trend toward minimalism.

PMID- 22381331
TI  - Brain abscesses: past and present.

PMID- 22381332
TI  - Evolved craniofacial surgery.

PMID- 22381333
TI  - The microsurgical treatment of cranio-orbital tumors assisted by intraoperative
      electrophysiologic monitoring and neuronavigation.
AB  - OBJECTIVE: Total resection of cranio-orbital tumors without any major
      complications is still a challenge for neurosurgeons. Intraoperative
      electrophysiologic monitoring and neuronavigational system have been widely used
      in microneurosurgery, but their effects during microsurgical treatment of cranio
      orbital tumors warrant further investigation. METHODS: Thirty-eight patients with
      cranio-orbital tumors admitted to our hospital underwent microsurgery assisted by
      intraoperative electrophysiologic monitoring. We also simultaneously performed
      intraoperative neuronavigation in 20 patients. A retrospective review of clinical
      notes, operation records and prognoses of all patients was performed. RESULTS:
      Gross total resection was achieved in 29 patients (76%), near total resection in
      5 (13%), subtotal resection in 3 (8%) and partial resection in 1 (3%). With the
      helps of electromyogram (EMG) monitoring of levator palpebrae superioris (LPS)
      muscle and navigation system, no surgical damages to the oculomotor nerve and
      other important structures occurred. A follow-up study showed that 31 patients
      (82%) resumed normal lives (Glasgow Outcome Scale (GOS) score 5), 5 patients
      (13%) had independent lives (GOS score 4), and 2 patients (5%) were unable to
      live independently (GOS score 3). CONCLUSION: Microsurgical treatment assisted by
      intraoperative electrophysiologic monitoring and neuronavigation might be a
      useful method for resection of cranio-orbital tumors, especially better for
      protection of the important cranial nerve and structure in the kull base.

PMID- 22381334
TI  - In vitro and in vivo metabolism and pharmacokinetics of BMS-562086, a potent and
      orally bioavailable corticotropin-releasing factor-1 receptor antagonist.
AB  - The absorption, distribution, metabolism, and excretion (ADME) and the
      pharmacokinetic characteristics of BMS-562086 [pexacerfont; 8-(6-methoxy-2-methyl
      3-pyridinyl)-2,7-dimethyl-N-[(1R)-1-methylpropyl]pyrazolo(1,5-a)-1,3,5-triazin-4
      amine (DPC-A69448)] were investigated in vitro and in animals to support its
      clinical development. BMS-562086 was orally bioavailable in rats, dogs, and
      chimpanzees, with an absolute oral bioavailability of 40.1, 58.8, and 58.5%,
      respectively. BMS-562086 was extensively metabolized in hepatocytes from all
      species and completely metabolized in rats. The primary biotransformation
      pathways found for BMS-562086 in both liver microsomal and hepatocyte
      preparations and in rats were similar. These included O-demethylation,
      hydroxylation at the N-alkyl side chain and N-dealkylation. Multiple cytochromes
      P450 including CYP3A4/5 were involved in the metabolic clearance of BMS-562086.
      Both renal and biliary excretion played a significant role in elimination of the
      metabolites of BMS-562086. The involvement of other metabolic enzymes in addition
      to CYP3A4/5 in elimination of BMS-562086 suggests a reduced potential for drug
      drug interaction through modulation of CYP3A4/5. Chimpanzees proved to be a good
      animal model in predicting BMS-562086 human clearance. Virtual clinical trials
      performed with a population-based ADME simulator suggested that a minimal dose of
      100 mg daily would provide sufficient drug exposure to achieve plasma
      concentrations above the projected human efficacious plasma concentration of BMS
      562086 (> 500 nM). In summary, BMS-562086 exhibited favorable ADME and
      pharmacokinetic properties for further development.

PMID- 22381335
TI  - In vitro evaluation of hepatic transporter-mediated clinical drug-drug
      interactions: hepatocyte model optimization and retrospective investigation.
AB  - To assess the feasibility of using sandwich-cultured human hepatocytes (SCHHs) as
      a model to characterize transport kinetics for in vivo pharmacokinetic
      prediction, the expression of organic anion-transporting polypeptide (OATP)
      proteins in SCHHs, along with biliary efflux transporters, was confirmed
      quantitatively by liquid chromatography-tandem mass spectrometry. Rifamycin SV
      (Rif SV), which was shown to completely block the function of OATP transporters,
      was selected as an inhibitor to assess the initial rates of active uptake. The
      optimized SCHH model was applied in a retrospective investigation of compounds
      with known clinically significant OATP-mediated uptake and was applied further to
      explore drug-drug interactions (DDIs). Greater than 50% inhibition of active
      uptake by Rif SV was found to be associated with clinically significant OATP
      mediated DDIs. We propose that the in vitro active uptake value therefore could
      serve as a cutoff for class 3 and 4 compounds of the Biopharmaceutics Drug
      Disposition Classification System, which could be integrated into the
      International Transporter Consortium decision tree recommendations to trigger
      clinical evaluations for potential DDI risks. Furthermore, the kinetics of in
      vitro hepatobiliary transport obtained from SCHHs, along with protein expression
      scaling factors, offer an opportunity to predict complex in vivo processes using
      mathematical models, such as physiologically based pharmacokinetics models.

PMID- 22381336
TI  - Multicatalytic asymmetric synthesis of complex tetrahydrocarbazoles via a Diels
      Alder/benzoin reaction sequence.
AB  - Expanding upon the recently developed aminocatalytic asymmetric indole-2,3
      quinodimethane strategy, a straightforward synthesis of structurally and
      stereochemically complex tetrahydrocarbazoles has been devised. The chemistry's
      complexity-generating power was further harnessed by designing a multicatalytic,
      one-pot Diels-Alder/benzoin reaction sequence to stereoselectively access trans
      fused tetracyclic indole-based compounds having four stereogenic centers with
      very high fidelity.

PMID- 22381337
TI  - Knockdown of Sec6 improves cell-cell adhesion by increasing alpha-E-catenin in
      oral cancer cells.
AB  - The Sec6/8 complex is essential for specific exocytic sites on the plasma
      membrane and contributes to membrane growth in mammalian cells. In Madin-Darby
      canine kidney (MDCK) cells, E-cadherin and nectin-based adhesion complexes
      recruit the Sec6/8 complex to intercellular contacts. However, in cancer cells,
      the relationship between the Sec6/8 complex and the cell-cell adhesion proteins
      remains obscure. We demonstrate that the expression of alpha-E-catenin is
      increased by Sec6 siRNAs, and E-cadherin and beta-catenin localize mainly at the
      cell-cell contact region in HSC3 cells, which were transfected with Sec6 siRNA.

PMID- 22381338
TI  - Incoming presidential address and new 2011 AOFAS Board of Directors.

PMID- 22381339
TI  - Correlation of weightbearing radiographs and stability of stress positive ankle
      fractures.
AB  - BACKGROUND: A positive external rotation stress test has been used as an
      indication for operative treatment of fractures of the lateral malleolus. The
      objective of the current study was to ascertain the results of a protocol
      initially treating stress positive ankle fractures nonoperatively and utilizing
      weightbearing radiographs in surgical decision making. METHODS: We performed a
      prospective study of lateral malleolar fractures with an associated medial
      ligamentous injury. All patients with fractures of the lateral malleolus with
      medial sided symptoms and/or signs, and an intact ankle mortise underwent an
      external rotation stress test to confirm injury to the deltoid ligament (stress
      positive). Patients with a positive stress test were placed in a short-leg
      walking cast and seen in 7 days where weightbearing radiographs of the ankle were
      obtained. If the radiographs demonstrated an intact mortise, then nonoperative
      treatment was continued. If the weightbearing radiographs demonstrated medial
      clear space widening, then the patient was offered operative treatment to restore
      the congruency of the ankle mortise. Patients were assessed for conversion to
      operative treatment, complications, and functional outcome. Thirty-eight patients
      were enrolled in the study. Using Lauge-Hansen classification 36 (95%) were
      stress positive supination-external rotation fractures and 2 (5%) were stress
      positive pronation-external rotation fractures. Followup assessment was performed
      at a minimum of 6 months and averaged 12 months. RESULTS: Weightbearing
      radiographs at the first post-injury clinic visit had an average medial clear
      space of 2.9 +/-0.9 mm. Three (8%) patients met our criteria for medial clear
      space widening and underwent operative treatment. Of these three patients, two
      were pronation-external rotation fracture patterns. Therefore, 3% of the
      supination-external rotation IV fractures, and all of the pronation-external
      III/IV rotation fractures ultimately required operative treatment. At final
      followup, the average AOFAS hindfoot score was 92 +/-8.1. CONCLUSION: Ligamentous
      supination-external rotation Stage IV fractures with an intact mortise on static
      radiographs can be initially treated nonoperatively. Weightbearing radiographs
      should be utilized to assess congruency of the ankle mortise during an early post
      injury visit. Utilizing this approach, a significant number of surgeries were
      avoided, and good to excellent results were obtained. From our early experience,
      nonoperative treatment of pronation-external rotation III/IV injuries using this
      protocol is not recommended.

PMID- 22381340
TI  - Percutaneous lateral ligament reconstruction with allograft for chronic lateral
      ankle instability.
AB  - BACKGROUND: The majority of lateral ankle instability can be treated successfully
      with conservative method. However, if such treatments fail, surgical treatment
      should be considered. A wide variety of procedures have been introduced to treat
      chronic lateral ankle instability. The percutaneous method avoids dissection
      which is associated with open surgery and can lead to excessive morbidity. The
      purpose of this study was to evaluate the clinical and radiological outcomes of
      percutaneous lateral ligament reconstruction with an allograft in the treatment
      of chronic lateral ankle instability. METHODS: Between October 2006 and April
      2009, percutaneous lateral ligament reconstruction using an allograft was
      performed on 15 ankles in 13 patients for chronic lateral ankle instability. The
      patients included in this study satisfied at least one of the following criteria:
      a previously failed reconstruction of the ligament, severe ankle instability
      (more than 15 degrees of talar tilt, more than 10 mm of anterior drawer), general
      laxity of ligaments, body mass index (BMI) higher than 25. The mean followup
      period was 18.1 (range, 12 to 40) months. The grafted tendon was secured by
      double tenodeses at both the talus and calcaneus or triple tenodeses which
      included a fibular tenodesis. The clinical outcomes were evaluated with Visual
      Analogue Scale (VAS) for pain, Karlsson-Peterson ankle score, and patients'
      subjective satisfaction. The radiological results were evaluated using the varus
      tilting angle and the anterior displacement distance. RESULTS: The VAS improved
      from preoperative 3.7 +/-2.2 to 1.6 +/-1.3 at the last followup (p = 0.002). The
      Karlsson-Peterson ankle score increased from 54.2 +/-8.8 to 80.9 +/-7.2 (p =
      0.001). Patients were satisfied in 13 cases (86.7%) with excellent or good
      results. Radiologically, the mean varus tilting angle was 15.5 +/-4.4 degrees
      preoperatively and 7.3 +/-3.6 at the last followup (p = 0.001). The anterior
      drawer distance was 10.1 +/-3.3 mm preoperatively and 7.2 +/-2.7 mm at last
      followup (p = 0.001). CONCLUSION: We believe percutaneous lateral ligament
      reconstruction with allograft to be a useful method as a salvage procedure for
      the treatment of severe and complicated types of chronic lateral ankle
      instability. Furthermore, the minimal invasiveness of this technique provides a
      good cosmetic outcome and we found it to be a technically easy and fast
      procedure.

PMID- 22381341
TI  - Early complications and recurrence rates after Kirschner wire transfixion in
      lesser toe surgery: a prospective randomized study.
AB  - BACKGROUND: Prolonged percutaneous Kirschner wire transfixion after correction of
      lesser toe deformities has been associated with an increased rate of
      complications such as infection, wire breakage or loosening. Currently, the
      duration of wire transfixion is based on the surgeons' opinion rather than on
      evidence. We hypothesized that a transfixion time of 3 weeks when compared to 6
      weeks would decrease complication rates without an increase in the rate of
      recurrent deformity. METHODS: We prospectively randomized 52 lesser toes
      corrected for a moderate hammer- or claw toe deformity by means of resectional
      arthroplasty of the proximal interphalangeal joint into two groups with 3 and 6
      weeks of Kirschner wire transfixion, respectively. Kirschner wire-associated
      complication rates and incidence of early recurrence of malalignment in a short
      term followup of three months were assessed. Forty-six toes, 23 in each group,
      were available for final followup. RESULTS: No statistically significant
      differences were found in pre- and postoperative total AOFAS scores between the
      groups. No Kirschner wire associated complications occurred. Recurrent
      malalignment was more often documented in the group with 3 weeks of transfixion
      (11 of 23 toes, 47.8%) when compared to 6 weeks (two of 23 toes, 8.7%) at 3
      months followup. Interphalangeal joint motion was significantly reduced with
      prolonged Kirschner wire transfixion, indicating a more stable fibrous union (p =
      0.038). CONCLUSION: At short-term followup, Kirschner wire transfixion of 6 weeks
      as opposed to 3 weeks showed a lower rate of recurrent malalignment without an
      increase in Kirschner wire associated complications.

PMID- 22381342
TI  - Surgical management of Charcot neuroarthropathy of the foot and ankle: a
      systematic review.
AB  - BACKGROUND: Charcot neuroarthropathy (CN) of the foot and ankle is an extremely
      challenging clinical dilemma and surgical management can be highly complicated.
      The current literature on this topic is comprised of manuscripts that are
      retrospective case series and expert opinions. Furthermore, surgery in patients
      with CN of the foot and ankle is guided by studies with low levels of evidence to
      support our current surgical practices. METHODS: A Medline/CINAHL search was
      performed and a systematic review of articles discussing the surgical management
      of CN was undertaken. RESULTS: Ninety-five articles fit the inclusion criteria
      for our study. As hypothesized, all reports detailing the surgical management of
      Charcot neuroarthropathy constituted Level IV or V evidence. CONCLUSION: Surgical
      algorithms for the treatment of CN of the foot are based almost entirely on level
      four or five evidence. Uncontrolled retrospective case series and case reports
      guide the use of exostectomy, fusion, and Achilles tendon lengthening for CN.
      There is inconclusive evidence concerning timing of treatment and use of
      different fixation methods. Prospective series and randomized studies, albeit
      difficult to perform, are necessary to support and strengthen current practice.

PMID- 22381343
TI  - Midterm outcome of modified Kidner procedure.
AB  - BACKGROUND: The results of modified Kidner procedures have generally been
      satisfactory at short-term followup. The objective of this study was to evaluate
      the midterm followup results including medial longitudinal arch height. METHODS:
      Forty-one patients (50 feet) with a symptomatic accessory navicular who underwent
      the modified Kidner procedure between July 1999 and February 2004 were evaluated.
      A midfoot AOFAS score, VAS score, and satisfaction rate were recorded. The talo
      first metatarsal (T-MT1), talo-calcaneal (TC), and calcaneal pitch (CP) angles
      were measured on plain radiographs. Average clinical and radiological followup
      periods were 88.4 +/-17.0 months and 85.7 +/-15.0 months, respectively. RESULTS:
      The mean preoperative and followup AOFAS scores were 40.8 +/-7.1 (range, 32 to
      57), and 88.4 +/-7.9 (range, 72 to 100), respectively (p < 0.01). The mean
      preoperative and followup VAS scores were 7.1 +/-1.0 (range, 4 to 9) and 1.8 +/
      1.0 (range, 0 to 5), respectively (p < 0.01). At last followup , the satisfaction
      rate was 82.0%. There were no significant differences between preoperative and
      followup T-MT1 (p = 1.00), TC (p = 0.84), and CP (p = 0.08) angles. Increased
      medial longitudinal arch was found in four of 16 feet in patients 15 years of age
      or younger with followup radiographs. CONCLUSION: We found the modified Kidner
      procedure could result in symptomatic relief and high satisfaction rate without a
      loss of arch height in any patient.

PMID- 22381344
TI  - Surgical treatment of non-diabetic chronic osteomyelitis involving the foot and
      ankle.
AB  - BACKGROUND: We evaluated the clinical characteristics and treatment outcomes of
      patients with chronic osteomyelitis in the foot and ankle in patients without
      diabetes. METHODS: We reviewed 15 patients treated for chronic osteomyelitis
      involving the foot and ankle between September 2004 and March 2007. Patients with
      diabetes mellitus or who were immunocompromised were excluded. The cause of
      osteomyelitis, sites of occurrence, causative pathogens, and invasion of the
      adjacent joint(s) were reviewed, then the clinical characteristics were analyzed.
      Magnetic resonance imaging was performed to clarify the extent of infection and
      invasion of the adjacent joint. Surgical management included wide debridement,
      dead space control, and arthrodesis if there was invasion of the adjacent joint.
      The mean postoperative followup period was 3.3 years, during which recurrences
      and complications were evaluated. RESULTS: Extrinsic causes accounted for 86.7%
      of the chronic osteomyelitis involving the foot and ankle. The most common cause
      of osteomyelitis was trauma with ten cases due to complications following
      fractures or dislocation. Methicillin-resistant Staphylococcus aureus and
      Pseudomonas were the most common causative pathogens. In 46.7% of the patients,
      the adjacent joint was involved and an arthrodesis was performed. The mean length
      of the hospital stay was 39.1 days. The average of number of surgeries was two.
      Fourteen of 15 patients had no recurrence. CONCLUSION: For the successful
      treatment of chronic osteomyelitis involving the foot and ankle, an arthrodesis
      based on invasion of the adjacent joint as well as wide debridement and dead
      space control was successful in this series.

PMID- 22381345
TI  - Metatarsophalangeal joint pathology in crossover second toe deformity: a
      cadaveric study.
AB  - BACKGROUND: Ligamentous and capsular insufficiency of the second
      metatarsophalangeal joint has been surgically treated for over two decades,
      mainly with indirect surgical repairs, which stabilize adjacent soft tissue and
      shorten or decompress the osseous structures. While ligamentous insufficiency has
      been described and recognized, degeneration of the plantar plate and tears of the
      capsule have rarely been documented. The purpose of this study was to document
      and describe the presence and pattern of plantar plate tears in specimens with
      crossover second toe deformities, and based on this, to develop an anatomical
      grading system to assist in the assessment and treatment of this condition.
      METHODS: Sixteen below-knee cadaveric specimens with a clinical diagnosis of a
      second crossover toe deformity were examined, and dissected by removing the
      metatarsal head. The pathologic findings of plantar plate and capsular pathology,
      as well as ligamentous disruption, were observed and recorded. Demographics of
      the specimens were recorded, and simulated weightbearing radiographs were
      obtained prior to dissection so that pertinent angular measurements could be
      obtained. RESULTS: Demographics demonstrated a high percentage of female
      specimens, and a typically older population that has been reported for this
      condition. Radiographic findings documented a high percentage of hallux valgus
      and hallux rigidus deformities. The MTP-2 and MTP-3 angles were divergent
      consistent with a crossover toe deformity. We consistently found transverse tears
      in the plantar plate region immediately proximal to the capsular insertion on the
      base of the proximal phalanx. With increasing deformity, wider distal transverse
      tears extending from lateral to medial were found. Midsubstance tears, collateral
      ligament tears, and complete disruption of the plantar plate were found in more
      severe deformities. CONCLUSION: In this largest series of cadaveric dissections
      of crossover second toe deformities, we describe the types and extent of plantar
      plate tears associated with increasing deformity of the second ray. We present,
      based on these findings, an anatomic grading system to describe the progressive
      anatomic changes in the plantar plate.

PMID- 22381346
TI  - Multisegmental foot and ankle motion analysis after hallux valgus surgery.
AB  - BACKGROUND: Gait changes in patients with hallux valgus, including altered
      kinematic and temporal-spatial parameters, have been documented in the
      literature. Although operative treatment can yield favorable clinical and
      radiographic results, restoration of normal gait in this population remains
      unclear. Segmental kinematic changes within the foot and ankle during ambulation
      after operative correction of hallux valgus have not been reported. The aim of
      this study was to analyze changes in multisegmental foot and ankle kinematics in
      patients who underwent operative correction of hallux valgus. METHODS: A 15
      camera Vicon Motion Analysis System was used to evaluate 24 feet in 19 patients
      with hallux valgus preoperatively and postoperatively. The Milwaukee Foot Model
      was used to characterize segmental kinematics and temporal-spatial parameters
      (TSPs). Preoperative and postoperative kinematics and TSPs were compared using
      paired nonparametric methods; comparisons with normative data were performed
      using unpaired nonparametric methods. Outcomes were evaluated using the SF-36
      assessment tool. RESULTS: Preoperatively, patients with hallux valgus showed
      significantly altered temporal-spatial and kinematic parameters. Postoperatively,
      kinematic analysis demonstrated restoration of hallux position to normal. Hallux
      valgus angles and intermetatarsal angles were significantly improved, and
      outcomes showed a significant increase in performance of physical activities.
      Temporal-spatial parameters and kinematics in the more proximal segments were not
      significantly changed postoperatively. CONCLUSION: Postoperative results
      demonstrated significant improvement in foot geometry and hallux kinematics in
      the coronal and transverse planes. However, the analysis did not identify
      restoration of proximal kinematics. CLINICAL RELEVANCE: Further investigation is
      necessary to explore possible causes/clinical relevance and appropriate treatment
      interventions for the persistently altered kinematics.

PMID- 22381347
TI  - Isolated spring ligament rupture causing acute flatfoot deformity: case report.

PMID- 22381348
TI  - Subtalar instability: diagnosis and treatment.
AB  - Subtalar instability is challenging to diagnose. It rarely follows a complete
      subtalar dislocation, an event more likely to result in subtalar pain, stiffness,
      and arthritis. By history, subtalar instability can be suggested by the patient's
      feeling of ankle instability, easy "rolling over," and a need to look at the
      ground constantly when walking. Clinical measures for inversion and eversion do
      not accurately reflect isolated subtalar motion, as soft tissue and other joint
      motion confound the examination. Stress radiographs have high false positive
      rates. Magnetic resonance imaging can show injured or disorganized ligaments
      suggestive of recurrent subtalar strain, but are not dynamic studies and cannot
      alone diagnose instability. Operative treatment, when elected, should focus on
      determining the source of the problem. Generally direct repair of the lateral
      ligaments is sufficient. Bony malalignment should always be considered especially
      in the setting when previous ligament reconstruction has failed.

PMID- 22381349
TI  - Valgus malalignment: what joints to address?

PMID- 22381350
TI  - Current concepts review: 3T magnetic resonance imaging of the ankle and foot.

PMID- 22381351
TI  - Delayed repair of right atrial isomerism with obstructed total anomalous
      pulmonary venous drainage by hybrid stent insertion between the left-sided atrium
      and pulmonary venous confluence.

PMID- 22381352
TI  - Building the niche: the role of the S100 proteins in metastatic growth.
AB  - Communication between cancer cells and stromal cells, often mediated by
      extracellular molecules in the tumor microenvironment, plays a central role in
      tumorigenesis and metastasis. The establishment of a pro-inflammatory milieu is
      increasingly recognized as an important consequence of these interactions. The
      family of S100 Ca2+-binding proteins has been implicated in many aspects of the
      interaction between cancer cells and stromal cells, and contributes to the
      formation of an inflammatory tumor microenvironment. Focusing on S100A4, S100A8
      and S100A9, in this review we discuss the role these proteins play in primary
      tumors and in the development of metastases, in particular during the formation
      of pre-metastatic niches.

PMID- 22381353
TI  - Sudden death of a child because of an intestinal obstruction caused by a large
      congenital mesenteric defect.
AB  - Transmesenteric hernias are internal hernias caused by a congenital defect in the
      mesentery. They are rare causes of intestinal obstruction, but most commonly
      affect the small bowel. We report an unexpected death of an infant with a bowel
      obstruction caused by a congenital mesenteric defect, which was undiagnosed
      despite visits to three different hospitals. Mesenteric defects are usually 2-3
      cm in diameter. At autopsy, we found an oval, 14 * 7 cm congenital defect in the
      ileal mesentery through which the small bowel had herniated. Diagnosis of such
      defects remains difficult, even with currently available imaging techniques.
      Diagnosis is particularly difficult in infants who usually have nonspecific
      symptoms. Therefore, it is important that sudden unexpected deaths in children
      undergo full forensic evaluation to establish the precise cause of death. It is
      also important for forensic physicians to inform clinicians of the risk of such
      diseases, particularly in emergency situations.

PMID- 22381354
TI  - Structure-activity studies on the anti-proliferation activity of ajoene analogues
      in WHCO1 oesophageal cancer cells.
AB  - The organosulfur compound ajoene derived from the rearrangement of allicin found
      in crushed garlic can inhibit the proliferation of tumour cells by inducing
      G(2)/M cell cycle arrest and apoptosis. We report on the application of a concise
      four-step synthesis (Hunter et al., 2008 [1]) that allows access to ajoene
      analogues with the end allyl groups substituted. A library of twelve such
      derivatives tested for their anti-proliferation activity against WHCO1
      oesophageal cancer cells has identified a derivative containing p-methoxybenzyl
      (PMB)-substituted end groups that is twelve times more active than Z-ajoene, with
      an IC(50) of 2.1MUM (Kaschula et al., 2011 [2]). Structure-activity studies
      involving modification of the sulfoxide and vinyl disulfide groups of this lead
      have revealed that the disulfide is the ajoene pharmacophore responsible for
      inhibiting WHCO1 cell growth, inducing G(2)/M cell cycle arrest and apoptosis by
      caspase-3 activation, and that the vinyl group serves to enhance the anti
      proliferation activity a further eightfold. Reaction of the lead with cysteine in
      refluxing THF as a model reaction for ajoene's mechanism of action based on a
      thiol/disulfide exchange reveals that the allylic sulfur of the vinyl disulfide
      is the site of thiol attack in the exchange.

PMID- 22381355
TI  - Design, synthesis and molecular docking studies of some novel spiro[indoline-3,
      4'-piperidine]-2-ones as potential c-Met inhibitors.
AB  - Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers
      and is considered as an attractive target for small molecule drug discovery. In
      this study, a series of spiro[indoline-3, 4'-piperidine]-2-ones were designed,
      synthesized and evaluated as novel c-Met inhibitors. The results showed that the
      majority of the compounds exhibited significant inhibitory effect on c-Met with
      IC(50) values of 0.0147-17 MUM in TR-FRET-based assay and IC(50) values of 1.56
      1400 MUM in cell-based assay. Furthermore, our docking experiments verified the
      results and explained the molecular mechanism of eminent activities to c-Met.

PMID- 22381356
TI  - Photoactivated DNA cleavage and anticancer activity of pyrenyl-terpyridine
      lanthanide complexes.
AB  - Lanthanide(III) complexes [Ln(R-tpy)(acac)(NO(3))(2)] (Ln = La(III) in 1, 2;
      Gd(III) in 4, 5) and [Ln(py-tpy)(sacac)(NO(3))(2)] (Ln = La(III), 3; Gd(III), 6),
      where R-tpy is 4'-phenyl-2,2':6',2"-terpyridine (ph-tpy in 1, 4), 4'-(1-pyrenyl)
      2,2':6',2"-terpyridine (py-tpy in 2, 3, 5 and 6), acac is acetylacetonate and
      sacac is 4-hydroxy-6-{4-[(beta-d-glucopyranoside)oxy]phenyl}hex-3,5-dien-2-onate,
      were prepared to study their DNA photocleavage activity and photocytotoxicity.
      Complexes [La(ph-tpy)(acac)(EtOH)(NO(3))(2)] (1a) and [Gd(ph
      tpy)(acac)(NO(3))(2)] (4) were characterized by X-ray crystallography. The 1:1
      electrolytic complexes bind to calf thymus DNA. The py-tpy complexes cleave pUC19
      DNA and exhibit remarkable photocytotoxicity in HeLa cells in UV-A light of 365
      nm with apoptotic cell death (IC(50): ~40 nM in light, >200 MUM in dark).
      Confocal microscopy using HeLa cells reveal primarily cytosolic localization of
      the complexes.

PMID- 22381357
TI  - New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active
      as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on
      mouse C2C12 skeletal muscle cells.
AB  - In pursuing our research targeting the identification of potent inhibitors of
      PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3
      thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory
      profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform
      IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely
      related TC-PTP. These compounds were found to activate the insulin-mediated
      signalling on mouse C2C12 skeletal muscle cells by increasing the phosphorylation
      levels of the insulin receptor and promoting cellular 2-deoxyglucose uptake.
      Interestingly, 4-{[5-(4-benzyloxybenzylidene)-2-(4-trifluoromethylphenylimino)-4
      oxo-3-thiazolidinyl]methyl}benzoic acid (7d), the best in vitro inhibitor of
      PTP1B and the isoform IF1 of LMW-PTP, provided the highest activation level of
      the insulin receptor and was found to be endowed with an excellent
      insulinomimetic effect on the selected cells. This compound therefore represents
      an interesting lead compound for developing novel PTP1B and LMW-PTP inhibitors
      which could be achieved by improving both its pharmacological profile and its
      potentiating effects on insulin signalling.

PMID- 22381358
TI  - Ferric haem forms of Mycobacterium tuberculosis catalase-peroxidase probed by EPR
      spectroscopy: Their stability and interplay with pH.
AB  - Low temperature EPR spectroscopy was used to characterise Mycobacterium
      tuberculosis catalase-peroxidase in its resting ferric haem state. Several high
      spin ferric haem forms and no low spin forms were found in the enzyme samples
      frozen in methanol on dry ice. The EPR spectra depended not only on the pH but
      also on the buffer type. As a general trend, the higher the pH, the greater the
      'rhombic' fraction of the high spin ferric haem that was observed. The rhombic
      form was characterised by well separated two lines in the g = 6 region whereas in
      the 'axial' form the two lines overlap. This pH dependence of the equilibrium of
      axial and rhombic ferric haem forms is also seen in rapidly freeze-quenched
      samples. Different high spin ferric haem forms were monitored during a 3 week
      storage of the enzyme at 4  degrees C. For some forms, extremal dependences, i.e.
      those progressing via maxima or minima over storage time, were found. This
      indicates that the mechanism of the time-dependent transition from one high spin
      ferric haem form to another must be more complex than a simple single site
      oxidation.

PMID- 22381359
TI  - Structural and inhibition insights into carbonic anhydrase CDCA1 from the marine
      diatom Thalassiosira weissflogii.
AB  - Carbonic anhydrases (CAs) catalyze with high efficiency the reversible hydration
      of carbon dioxide, an essential reaction for many biological processes, such as
      photosynthesis, respiration, renal tubular acidification, and bone resorption.
      Diatoms, which are one of the most common types of phytoplankton and are
      widespread in oceans, possess CAs fundamental for acquisition of inorganic
      carbon. Recently, in the marine diatom Thalassiosira weissflogii a novel enzyme,
      CDCA1, naturally using Cd in its active site, has been isolated and categorized
      in a new CA class, namely zeta-CA. This enzyme, which consists of three repeats
      (R1, R2 and R3), is a cambialistic carbonic anhydrase that can spontaneously
      exchange Zn or Cd at its active centre, presumably an adaptative advantage for
      diatoms that grow fast in the metal-poor environment of the surface ocean. In
      this paper we completed the characterization of this enzyme, reporting the X-ray
      structure of the last repeat, CDCA1-R3 in its cadmium-bound form, and presenting
      a model of the full length protein obtained by docking approaches. Results show
      that CDCA1 has a quite compact not symmetric structure, characterized by two
      covalently linked R1-R2 and R2-R3 interfaces and a small non-covalent R1-R3
      interface. The three dimensional arrangement shows that most of the non-conserved
      aminoacids of the three repeats are located at the interface regions and that the
      active sites are far from each other and completely accessible to the substrate.
      Finally, a detailed inhibition study of CDCA1-R3 repeat in both cadmium- and zinc
      bound form has been performed with sulfonamides and sulfamates derivatives. The
      results have been compared with those previously reported for other CA classes,
      namely alpha- and beta-classes, and correlated with the structural features of
      these enzymes.

PMID- 22381360
TI  - [Risk of cancer in patients following chronic dialysis and kidney graft].
AB  - BACKGROUND: A high prevalence of renal insufficiency has been observed in cancer
      patients as well as a high incidence of de novo cancer in dialysis or renal
      transplant patients. MATERIAL AND METHODS: We aimed to determine the incidence of
      cancer in patients under dialysis and in kidney transplant recipients through a
      search of the literature. RESULTS: Under chronic dialysis, the risk of cancer
      increases from 1.1 to 1.8 in comparison to the general population. These risks
      reach 2.5 to 3.9 in renal transplant patients, but depend on the type of tumor.
      CONCLUSION: In transplant recipients, the risk of cancer induced by
      immunosuppressive therapy requires a specific follow-up and a screening for any
      medical history of cancer in the donor and the recipient.

PMID- 22381361
TI  - Paediatric sutureless circumcision and modified circumcision: video
      demonstration.
AB  - OBJECTIVE: Circumcision is undertaken using a variety of surgical methods.
      Modified circumcision for the hooded prepuce or mild glanular hypospadias
      mandates an excellent cosmetic result. Tissue glue is an alternative to sutures
      for circumcision in children and has significant advantages in terms of cosmesis
      and postoperative pain. We present two detailed videos demonstrating our
      technique for sutureless circumcision and modified circumcision. METHOD: The
      incisions were marked on the outer and inner preputial skin. Incisions were made
      with a scalpel. Complete haemostasis was ensured. Tissue adhesive was placed onto
      the wound using a 32-gauge needle to allow controlled application. It is
      important to ensure that the coronal sulcus is free of glue at the end of the
      procedure. Once the circumcision is complete the penis can be cleaned and
      temporarily dressed. RESULTS: Between November 2008 and September 2011, we have
      used this technique for 57 circumcisions and 30 modified circumcisions. No
      complications occurred. All were followed up for a minimum of 3-6 months.
      CONCLUSION: The technique allows reproducible excellent cosmetic results, can be
      easily taught to junior surgical staff and should be considered as an alternative
      to a standard sutured circumcision.

PMID- 22381362
TI  - Longitudinal functional performance among children with cochlear implants and
      disabilities: a prospective study using the Pediatric Evaluation of Disability
      Inventory.
AB  - OBJECTIVE: Functional outcomes are important in children with cochlear implants
      (CI) and additional disabilities as studies on auditory skill and speech/language
      development may not identify functional benefits from implantation. This study
      sought to measure functional performance skills of young children with
      developmental disabilities post-CI. METHODS: Eight children with cognitive
      disabilities undergoing cochlear implantation were enrolled in a prospective
      study of language and functional abilities; 6 with 1 year follow-up were included
      in the analysis. Functional performance was measured using Pediatric Evaluation
      of Disability Inventory (PEDI), providing standardized (mean: 50) and scaled
      scores (range: 0-100) of functional domains: Self-Care, Mobility and Social
      Function. The PEDI was administered pre-implant, 6 and 12 months post
      implantation along with language testing at the same intervals. RESULTS: All
      children had cognitive disability; 5 also had motor delay. The ages at CI ranged
      from 13.8 to 134 months. For functional abilities, children did not make
      significant changes in domain-specific standard scores over 1 year. Children made
      progress in scaled scores by 1-year post-implant. The largest increase for all
      domains occurred in the first 6 months (7-11.5 point increase). For language
      abilities, children made a median 5.5-month increase in receptive language age
      (p=0.06) and 5-month increase in expressive language age (p=0.03) in the first
      year post-CI with no change in language quotients. Receptive language level was
      significantly (p<0.05) associated with increasing scores in the domains of Self
      Care and Social Function. CONCLUSIONS: This is the first study to measure daily
      functional abilities in children with implants and disabilities using a
      standardized tool. Although our small group of complex children did not have an
      increase in standard scores (gap-closing trajectories), they made progress in
      skill development on scaled scores. Receptive language appears to play a key role
      in social functioning in this population. Functional assessments are informative
      for treatment planning and identifying specific areas to target intervention.

PMID- 22381363
TI  - Noma in an Afghani child: a case report.
AB  - We present a case of Cancrum Oris, also known as Noma, in a child treated by an
      Otorhinolaryngologist at a United States-led Joint Forces hospital in
      Afghanistan. Noma is a deadly, necrotizing infection of the face that is rarely
      seen in wealthy nations but can cause significant morbidity in third world
      countries. Through a literature review, we report the incidence, risk factors,
      clinical features, and proposed treatment for this disease.

PMID- 22381364
TI  - Real-time polymerase chain reaction in the diagnosis of acute postoperative
      endophthalmitis.
AB  - PURPOSE: To evaluate the efficacy of quantitative real-time polymerase chain
      reaction (qPCR) in the diagnosis of postoperative bacterial endophthalmitis among
      patients who underwent cataract surgery at a tertiary care center. DESIGN:
      Prospective experimental study. METHODS: This was a single-center study of 64
      eyes of 64 patients presenting with clinical signs and symptoms of
      endophthalmitis within 1 year of cataract surgery. Patients with glaucoma
      filtering or cornea surgery in the past year, postoperative trauma, fungal
      endophthalmitis, or preoperative inflammatory conditions were excluded. Vitreous
      samples were obtained during vitreous tap or vitrectomy and sent for both culture
      and qPCR with sequencing. Vitreous samples obtained from 50 patients undergoing
      vitrectomy for noninflammatory indications served as controls. The main outcome
      measures were the sensitivity of qPCR compared to culture and concordance of
      results of pathogen identification with sequencing vs phenotypic speciation.
      RESULTS: qPCR detected 16s bacterial DNA in 37 patients (66%), compared to 19
      (34%) with traditional culture. Only 1 patient had a positive result by culture
      (Nocardia species) but negative result by qPCR. For the 18 samples positive by
      both qPCR and culture, there was a 100% concordance in pathogen identification
      between sequencing and phenotypic speciation. CONCLUSION: In cases of suspected
      bacterial endophthalmitis, qPCR offers an improved diagnostic yield and may be a
      useful adjunct to traditional culture. Further large-scale clinical studies are
      needed to elucidate the full clinical utility of qPCR.

PMID- 22381366
TI  - Development of a fluorescence polarization binding assay for asialoglycoprotein
      receptor.
AB  - Asialoglycoprotein receptor (ASGP-R) has been actively investigated for targeted
      delivery of therapeutic agents into hepatocytes because this receptor is
      selectively and highly expressed in liver and has a high internalization rate.
      Synthetic cluster glycopeptides (e.g., triGalNAc) bind with high affinity to ASGP
      R and, when conjugated to a therapeutic agent, can drive receptor-mediated uptake
      in liver. We developed a novel fluorescent polarization (FP) ASGP-R binding assay
      to determine the binding affinities of ASGP-R-targeted molecules. The assay was
      performed in 96-well microplates using membrane preparations from rat liver as a
      source of ASGP-R and Cy5 fluorophore-labeled triGalNAc synthetic ligand as a
      tracer. This high-throughput homogeneous assay demonstrates advantages over
      existing multistep methods in that it minimizes both time and resources spent in
      determining binding affinities to ASGP-R. At the optimized conditions, a Z'
      factor of 0.73 was achieved in a 96-well format.

PMID- 22381365
TI  - The short-term effects of antioxidant and zinc supplements on oxidative stress
      biomarker levels in plasma: a pilot investigation.
AB  - PURPOSE: To determine if short-term Age-Related Eye Disease Study (AREDS)
      antioxidant and zinc supplementation affects biomarkers of oxidative stress,
      possibly serving as a predictor of their efficacy. DESIGN: Prospective
      interventional case series. METHODS: Nineteen subjects, 12 with intermediate or
      advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7
      non-AMD controls, were admitted to the Vanderbilt General Clinical Research
      Center and placed on a controlled diet for 7 days. Antioxidant and zinc
      supplements were stopped 2 weeks prior to study enrollment. Dietary
      supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene, 80
      mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood
      was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys),
      cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were
      determined. RESULTS: Short-term AREDS supplementation significantly lowered mean
      plasma levels of CySS in participants on a regulated diet (P = .034). No
      significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no
      significant differences between AMD patients and controls. CONCLUSIONS: This
      pilot interventional study shows that a 5-day course of antioxidant and zinc
      supplements can modify plasma levels of CySS, suggesting that this oxidative
      stress biomarker could help predict how likely an individual is to benefit from
      AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD
      therapies, particularly those hypothesized to affect redox status.

PMID- 22381367
TI  - Microplate biochemical determination of Russian VX: influence of admixtures and
      avoidance of false negative results.
AB  - Two microplate spectroscopic methods for determination of organophosphates, based
      on inhibition of acetylcholinesterase (AChE) activity, were further improved and
      evaluated for determination of the chemical weapon agent Russian VX (RVX) in
      aqueous solutions. The linear range of the Hestrin method (74.8-1120 pM) was 3.1
      fold wider than that of the Ellman method (37.4-374 pM). Limits of detection and
      quantification of RVX for both methods were below the maximal allowable
      concentration of RVX in water-soluble washouts. One of the early products of RVX
      hydrolysis, N,N-diethylaminoethanethiol, like reduced glutathione, caused false
      negative results in the Ellman method at concentrations exceeding 10 MUM;
      individual blanks were necessary to eliminate the effect. The Hestrin method
      showed greater specificity (~3 orders of magnitude) for analysis of samples
      containing mercaptans. A major product of RVX degradation, 2,2'-dithiobis(N,N
      diethylethanamine), caused significant inhibition of AChE at concentrations of
      >=0.1 mM (P<0.01) and had a false positive effect at higher concentrations (>=2
      mM). For environmental monitoring of RVX, the method based on Hestrin is
      preferred over that based on Ellman, principally because the former method was
      less sensitive to interference from major admixtures and did not give rise to
      potentially dangerous false negative results.

PMID- 22381368
TI  - A continuous fluorescent enzyme assay for early steps of lipid A biosynthesis.
AB  - UDP-N-acetylglucosamine acyltransferase (LpxA) and UDP-3-O-(R-3-hydroxyacyl)
      glucosamine acyltransferase (LpxD) catalyze the first and third steps of lipid A
      biosynthesis, respectively. Both enzymes have been found to be essential for
      survival among gram-negative bacteria that synthesize lipopolysaccharide and are
      viable targets for antimicrobial development. Catalytically, both
      acyltransferases catalyze an acyl-acyl carrier protein (ACP)-dependent transfer
      of a fatty acyl moiety to a UDP-glucosamine core ring. Here, we exploited the
      single free thiol unveiled on holo-ACP after transfer of the fatty acyl group to
      the glucosamine ring using the thiol-specific labeling reagent, ThioGlo. The
      assay was continuously monitored as a change in fluorescence at lambda(ex)=379 nm
      and lambda(em)=513 nm using a microtiter plate reader. This assay marks the first
      continuous and nonradioactive assay for either acyltransferase.

PMID- 22381369
TI  - Rapid and sensitive determination of the intermediates of advanced glycation end
      products in the human nail by ultra-performance liquid chromatography with
      electrospray ionization time-of-flight mass spectrometry.
AB  - The resolution of the intermediate advanced glycation end products (AGEs) in the
      human nail was carried out by the combination of 4,5-dimethyl-1,2
      phenylenediamine (DMPD) derivatives and ultra-performance liquid chromatography
      with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-TOF-MS).
      The reaction of the reagent with 3-deoxyglucosone (3-DG), methylglyoxal (MG), and
      glyoxal (GO) effectively proceeds at 60 degrees C for 2h. The resulting
      derivatives were efficiently separated by a gradient program (a mixture of water
      and acetonitrile containing 0.1% formic acid) using a reversed-phase ACQUITY UPLC
      BEH C(18) column (1.7 MUm, 50*2.1 mm i.d.) and sensitively detected by TOF-MS.
      The detection limits (signal-to-noise ratio=5) of the TOF-MS were 10 to 50 fmol.
      A good linearity was achieved from the calibration curve, which was obtained by
      plotting the peak area ratios of the analytes relative to the internal standard
      (IS) (i.e., 2,3-hexanedione) versus the injected amounts of 3-DG, MG, and GO
      (r(2)>0.999), and the intra- and interday assay precisions were less than 6.89%.
      The derivatives of the compounds in the human nail were successfully identified
      by the proposed procedure. As we know, these three kinds of dicarbonyl
      intermediates in the formation of AGEs-3-DG, MG, and GO-were first found in human
      nail samples. Using these methods, the amounts of compound in the nails of
      healthy volunteers and diabetic patients were determined. When comparing the
      index from the diabetic patients with that from healthy volunteers, there is no
      significant difference in the content of the MG and GO in the nails. However, a
      statistically significant (P<0.001) correlation was observed between the 3-DG
      concentrations. Because the proposed method provides a good mass accuracy and the
      trace detection of the dicarbonyl intermediates of AGEs in the human nail, this
      analytical technique could be a noninvasive technique to assist in the diagnosis
      and assessment of disease activity in diabetic patients. Here we present a novel,
      sensitive, and simple method for the simultaneous determination of dicarbonyl
      compounds in the human nail.

PMID- 22381370
TI  - Radiochemical high-performance liquid chromatography detection of arginine
      metabolism in human endothelial cells.
AB  - Arginine is a semi-essential amino acid that plays an important role in the
      regulation of metabolic processes associated with several
      pathological/physiological conditions. In the vasculature, it mainly exerts its
      biological functions as a substrate of two alternative pathways: the conversion
      to nitric oxide (NO) by nitric oxide synthase (NOS) and the breakdown to urea and
      ornithine by arginase. To determine arginine metabolism, in the current study we
      propose an original radiochemical technique that allows the simultaneous
      monitoring of NOS and arginase activation within intact cells. Taking advantage
      of this method, we show here the consequences of different experimental
      conditions known to modulate endothelial homeostasis on arginine metabolism.

PMID- 22381371
TI  - Characteristics of third-generation glucose biosensors based on Corynascus
      thermophilus cellobiose dehydrogenase immobilized on commercially available
      screen-printed electrodes working under physiological conditions.
AB  - In this article, we describe a third-generation amperometric glucose biosensor
      working under physiological conditions. This glucose biosensor consists of a
      recently discovered cellobiose dehydrogenase from the ascomycete Corynascus
      thermophilus (CtCDH) immobilized on different commercially available screen
      printed electrodes made of carbon (SPCEs), carboxyl-functionalized single-walled
      carbon nanotubes (SPCE-SWCNTs), or multiwalled carbon nanotubes (SPCE-MWCNTs) by
      simple physical adsorption or a combination of adsorption followed by cross
      linking using poly(ethyleneglycol) (400) diglycidyl ether (PEGDGE) or
      glutaraldehyde (GA). The CtCDH-based third-generation glucose biosensor has a
      linear range between 0.025 and 30 mM and a detection limit of 10 MUM glucose.
      Biosensors based on SWCNTs showed a higher sensitivity and catalytic response
      than the ones functionalized with MWCNTs and the SPCEs. A drastic increase in
      response was observed for all three electrodes when the adsorbed enzyme was cross
      linked with PEGDGE or GA. The operational stability of the biosensor was tested
      for 7 h by repeated injections of 50 mM glucose, and only a slight decrease in
      the electrochemical response was found. The selectivity of the CtCDH-based
      biosensor was tested on other potentially interfering carbohydrates such as
      mannose, galactose, sucrose, and fucose that might be present in blood. No
      significant analytical response from any of these compounds was observed.

PMID- 22381372
TI  - Decolourisation of dyes under electro-Fenton process using Fe alginate gel beads.
AB  - This study focuses on the application of electro-Fenton technique by use of
      catalytic activity of Fe alginate gel beads for the remediation of wastewater
      contaminated with synthetic dyes. The Fe alginate gel beads were evaluated for
      decolourisation of two typical dyes, Lissamine Green B and Azure B under electro
      Fenton process. After characterization of Fe alginate gel beads, the pH effect on
      the process with Fe alginate beads and a comparative study of the electro-Fenton
      process with free Fe and Fe alginate bead was done. The results showed that the
      use of Fe alginate beads increases the efficiency of the process; moreover the
      developed particles show a physical integrity in a wide range of pH (2-8). Around
      98-100% of dye decolourisation was obtained for both dyes by electro-Fenton
      process in successive batches. Therefore, the process was performed with Fe
      alginate beads in a bubble continuous reactor. High color removal (87-98%) was
      attained for both dyes operating at a residence time of 30 min, without
      operational problems and maintaining particle shapes throughout the oxidation
      process. Consequently, the stable performance of Fe alginate beads opens
      promising perspectives for fast and economical treatment of wastewater polluted
      by dyes or similar organic contaminants.

PMID- 22381373
TI  - Toxicity assessment of zebrafish following exposure to CdTe QDs.
AB  - CdTe quantum dots (QDs) are nanocrystals of unique composition and properties
      that have found many new commercial applications; therefore, their potential
      toxicity to aquatic organisms has become a hot research topic. The lab study was
      performed to determine the developmental and behavioral toxicities to zebrafish
      under continuous exposure to low concentrations of CdTe QDs (1-400 nM) coated
      with thioglycolic acid (TGA). The results show: (1) the 120 h LC(50) of 185.9 nM,
      (2) the lower hatch rate and body length, more malformations, and less heart beat
      and swimming speed of the exposed zebrafish, (3) the brief burst and a higher
      basal swimming rate of the exposed zebrafish larvae during a rapid transition
      from light-to-dark, and (4) the vascular hyperplasia, vascular bifurcation,
      vascular crossing and turbulence of the exposed FLI-1 transgenic zebrafish
      larvae.

PMID- 22381374
TI  - Chemical speciation of size-segregated floor dusts and airborne magnetic
      particles collected at underground subway stations in Seoul, Korea.
AB  - Previous studies have reported the major chemical species of underground subway
      particles to be Fe-containing species that are generated from wear and friction
      processes at rail-wheel-brake and catenaries-pantographs interfaces. To examine
      chemical composition of Fe-containing particles in more details, floor dusts were
      collected at five sampling locations of an underground subway station. Size
      segregated floor dusts were separated into magnetic and non-magnetic fractions
      using a permanent magnet. Using X-ray diffraction (XRD) and scanning electron
      microscopy/energy dispersive X-ray spectrometry (SEM/EDX), iron metal, which is
      relatively harmless, was found to be the dominating chemical species in the floor
      dusts of the <25 MUm size fractions with minor fractions of Mg, Al, Si, Ca, S,
      and C. From SEM analysis, the floor dusts of the <25 MUm size fractions collected
      on railroad ties appeared to be smaller than 10 MUm, indicating that their
      characteristics should somewhat reflect the characteristics of airborne particles
      in the tunnel and the platform. As most floor dusts are magnetic, PM levels at
      underground subway stations can be controlled by removing magnetic indoor
      particles using magnets. In addition, airborne subway particles, most of which
      were smaller than 10 MUm, were collected using permanent magnets at two
      underground subway stations, namely Jegi and Yangjae stations, in Seoul, Korea.
      XRD and SEM/EDX analyses showed that most of the magnetic aerosol particles
      collected at Jegi station was iron metal, whereas those at Yangjae station
      contained a small amount of Fe mixed with Na, Mg, Al, Si, S, Ca, and C. The
      difference in composition of the Fe-containing particles between the two subway
      stations was attributed to the different ballast tracks used.

PMID- 22381375
TI  - The role of SRC family kinases in neuroendocrine tumors.

PMID- 22381377
TI  - A very obscure gastrointestinal bleeding.

PMID- 22381378
TI  - Complete mitochondrial genome of Coelomactra antiquata (Mollusca: Bivalvia): The
      first representative from the family Mactridae with novel gene order and unusual
      tandem repeats.
AB  - The complete mitochondrial genome plays an important role in the accurate
      inference of phylogenetic relationships among metazoans. Mactridae, also known as
      trough shells or duck clams, is an important family of marine bivalve clams in
      the order Veneroida. Here we present the complete mitochondrial genome sequence
      of the Xishishe Coelomactra antiquata (Mollusca: Bivalvia), which is the first
      representative from the family Mactridae. The mitochondrial genome of C.
      antiquata is of 17,384bp in length, and encodes 35 genes, including 12 protein
      coding, 21 transfer RNA, and 2 ribosomal RNA genes. Compared with the typical
      gene content of animal mitochondrial genomes, atp8 and tRNAS(2) are missing. Gene
      order of the mitochondrial genome of C. antiquata is unique compared with others
      from Veneroida. In the mitochondrial genome of the C. antiquata, a total of
      2189bp of non-coding nucleotides are scattered among 26 non-coding regions. The
      largest non-coding region contains one section of tandem repeats (99 bp*11),
      which is the second largest tandem repeats found in the mitochondrial genomes
      from Veneroida. The phylogenetic trees based on mitochondrial genomes support the
      monophyly of Veneridae and Lucinidae, and the relationship at the family level:
      ((Veneridae+Mactridae)+(Cardiidae+Solecurtidae))+Lucinidae. The phylogenetic
      result is consistent with the morphological classification. Meanwhile, bootstrap
      values are very high (BP=94-100), suggesting that the evolutionary relationship
      based on mitochondrial genomes is very reliable.

PMID- 22381379
TI  - Factors affecting the actions and emotional reactions of nursing teachers
      following encounters with students who present them with Internet information.
AB  - OBJECTIVE: The Internet is a preferred source of information for nursing
      students. The purpose of the research was to identify teachers' reactions towards
      students who present them with information retrieved from the Internet. METHOD: A
      total of 137 nursing teachers from 15 nursing schools in Israel were surveyed by
      a questionnaire. The dependent variable was nursing teachers' actions following
      encounters with students who present them with information from the Internet.
      Independent variables were: teacher's emotional reactions, teachers' Internet
      efficacy, Internet anxiety, and perceived student Internet efficacy. RESULTS: The
      intensity of positive emotional reactions was the only predictor of teachers'
      actions towards Internet information retrieved by students. When teachers
      perceived students as having higher Internet efficacy, their emotional reactions
      were more positive and they took more actions. Teachers' Internet anxiety was
      negatively correlated with their positive emotional reactions and actions. No
      correlation was found between nursing teachers' Internet self efficacy and their
      reactions or actions following an encounter with students presenting Internet
      information. Positive emotional reactions mediated correlations between teachers'
      Internet anxiety, perceived student Internet efficacy, and teachers' actions.
      CONCLUSIONS: Nursing teachers' positive emotions foster openness and acceptance
      of Internet information retrieved by students.

PMID- 22381380
TI  - Time to end the vagaries of PhD examining?

PMID- 22381381
TI  - Improving access to quality clinical nurse teaching--a partnership between
      Australia and Vietnam.
AB  - Until recently, standards to guide nursing education and practice in Vietnam were
      nonexistent. This paper describes the development and implementation of a
      clinical teaching capacity building project piloted in Hanoi, Vietnam. The
      project was part of a multi-component capacity building program designed to
      improve nurse education in Vietnam. Objectives of the project were to develop a
      collaborative clinically-based teaching model that encourages evidence-based,
      student-centred clinical learning. The model incorporated strategies to promote
      development of nursing practice to meet national competency standards. Thirty
      nurse teachers from two organisations in Hanoi participated in the program. These
      participants attended three workshops, and completed applied assessments, where
      participants implemented concepts from each workshop. The assessment tasks were
      planning, implementing and evaluating clinical teaching. On completion of the
      workshops, twenty participants undertook a study tour in Australia to refine the
      teaching model and develop an action plan for model implementation in both
      organisations, with an aim to disseminate the model across Vietnam. Significant
      changes accredited to this project have been noted on an individual and
      organisational level. Dissemination of this clinical teaching model has commenced
      in Ho Chi Minh, with further plans for more in-depth dissemination to occur
      throughout the country.

PMID- 22381383
TI  - How to develop a standard operating procedure for sorting unfixed cells.
AB  - Written standard operating procedures (SOPs) are an important tool to assure that
      recurring tasks in a laboratory are performed in a consistent manner. When the
      procedure covered in the SOP involves a high-risk activity such as sorting
      unfixed cells using a jet-in-air sorter, safety elements are critical components
      of the document. The details on sort sample handling, sorter set-up, validation,
      operation, troubleshooting, and maintenance, personal protective equipment (PPE),
      and operator training, outlined in the SOP are to be based on careful risk
      assessment of the procedure. This review provides background information on the
      hazards associated with sorting of unfixed cells and the process used to arrive
      at the appropriate combination of facility design, instrument placement, safety
      equipment, and practices to be followed.

PMID- 22381384
TI  - Interpreting protein structural dynamics from NMR chemical shifts.
AB  - In this investigation, semiempirical NMR chemical shift prediction methods are
      used to evaluate the dynamically averaged values of backbone chemical shifts
      obtained from unbiased molecular dynamics (MD) simulations of proteins. MD
      averaged chemical shift predictions generally improve agreement with experimental
      values when compared to predictions made from static X-ray structures. Improved
      chemical shift predictions result from population-weighted sampling of multiple
      conformational states and from sampling smaller fluctuations within
      conformational basins. Improved chemical shift predictions also result from
      discrete changes to conformations observed in X-ray structures, which may result
      from crystal contacts, and are not always reflective of conformational dynamics
      in solution. Chemical shifts are sensitive reporters of fluctuations in backbone
      and side chain torsional angles, and averaged (1)H chemical shifts are
      particularly sensitive reporters of fluctuations in aromatic ring positions and
      geometries of hydrogen bonds. In addition, poor predictions of MD-averaged
      chemical shifts can identify spurious conformations and motions observed in MD
      simulations that may result from force field deficiencies or insufficient
      sampling and can also suggest subsets of conformational space that are more
      consistent with experimental data. These results suggest that the analysis of
      dynamically averaged NMR chemical shifts from MD simulations can serve as a
      powerful approach for characterizing protein motions in atomistic detail.

PMID- 22381385
TI  - Evaluation of health-care utilization among adult patients with epilepsy in
      Germany.
AB  - This study evaluated the resource use of patients with epilepsy in the German
      district of Marburg-Biedenkopf. A cross-sectional cohort of consecutive adults
      with epilepsy, irrespective of seizure severity, duration of illness and epilepsy
      syndrome, was investigated in all health-care sectors. Costs of inpatient and
      outpatient treatment were derived from billing data of participating hospitals
      and office-based physicians. Data on socioeconomic status, course of epilepsy and
      further direct and indirect costs were recorded using patient questionnaires. We
      enrolled 366 patients from the district of Marburg-Biedenkopf and calculated
      annual epilepsy-specific costs of ?7738 per patient. Direct costs contributed
      31.1% (?2406) and indirect costs 68.9% (?5332) of the total costs. Direct medical
      costs were mainly due to hospitalization (33.2% of total direct costs) and
      anticonvulsants (26.7%). Costs of admissions were due to status epilepticus
      (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and
      seizure-related injuries (8.8%). Indirect costs were mainly due to early
      retirement (38.0%), unemployment (35.9%) and days off due to seizures (26.2%).
      The mean costs of epilepsy found in our study were lower than those found in
      studies conducted at European epilepsy centers due to the inclusion of patients
      in all health-care sectors.

PMID- 22381386
TI  - Epilepsy and autism: is there a special relationship?
AB  - Increasingly, there has been an interest in the association between epilepsy and
      autism. The high frequency of autism in some of the early-onset developmental
      encephalopathic epilepsies is frequently cited as evidence of the relationship
      between autism and epilepsy. While these specific forms of epilepsy carry a
      higher-than-expected risk of autism, most, if not all, of the association may be
      due to intellectual disability (ID). The high prevalence of interictal EEG
      discharges in children with autism is also cited as further evidence although
      errors in the diagnosis of epilepsy seem to account for at least part of those
      findings. The prevalence of ID is substantially elevated in children with either
      epilepsy or autism. In the absence of ID, there is little evidence of a
      substantial, if any, increased risk of autism in children with epilepsy. Further,
      although the reported prevalence of autism has increased over the last several
      years, much of this increase may be attributable to changes in diagnostic
      practices, conceptualization of autism in the presence of ID, and laws requiring
      provision of services for children with autism. In the context of these temporal
      trends, any further efforts to tease apart the relationships between epilepsy,
      ID, and autism will have to address head-on the accuracy of diagnosis of all
      three conditions before we can determine whether there is, indeed, a special
      relationship between autism and epilepsy.

PMID- 22381387
TI  - Default mode network abnormalities in idiopathic generalized epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) is associated with widespread cortical
      network abnormalities on electroencephalography. Resting state functional
      connectivity (RSFC), based on fMRI, can assess the brain's global functional
      organization and its disruption in clinical conditions. We compared RSFC
      associated with the 'default mode network' (DMN) between people with IGE and
      healthy controls. Strength of functional connectivity within the DMN associated
      with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices
      (MPFC) was compared between people with IGE and healthy controls and was
      correlated with seizure duration, age of seizure onset and age at scan. Those
      with IGE showed markedly reduced functional network connectivity between anterior
      and posterior cortical seed regions. Seizure duration positively correlates with
      RSFC between parahippocampal gyri and the PCC but negatively correlates with
      connectivity between the PCC and frontal lobe. The observed pattern of disruption
      provides evidence for integration- and segregation-type network abnormalities and
      supports aberrant network organization among people with IGE.

PMID- 22381388
TI  - Acute confusional state of unknown cause in the elderly: a study with continuous
      EEG monitoring.
AB  - INTRODUCTION: Acute confusional state (ACS) is a frequent cause of emergency
      consultation in the elderly. Many causes of ACS are also risk factors for
      seizures. Both non-convulsive seizures and status epilepticus can cause acute
      confusion. The yield of routine EEG may not be optimal in case of prolonged post
      ictal confusion. We thus, sought to evaluate the yield of CEEG in identifying
      seizures in elderly patients with ACS of unknown origin. METHODS: We reviewed our
      CEEG database for patients over 75 years with ACS and collected EEG, CEEG and
      clinical information. RESULTS: Thirty-one percent (15/48) of the CEEG performed
      in elderly patients were done for ACS. Routine EEG did not reveal any epileptic
      anomalies in 7/15 patients. Among those, CEEG identified interictal epileptiform
      discharges (IED) in 2 and NCSE in 1. In 8/15 patients, routine EEG revealed
      epileptiform abnormalities: 3 with IED (including 1 with periodic lateralized
      discharges), 3 with non-convulsive seizures (NCSz) and 2 with non-convulsive
      status epilepticus (NCSE). Among patients with only IED, CEEG revealed NCSz in 1
      and NCSE in 2. CONCLUSION: This retrospective study suggests that NCSz and NCSE
      may account for more cases of ACS than what was previously thought. A single
      negative routine EEG does not exclude this diagnosis. Continuous EEG (CEEG)
      monitoring is more revealing than routine EEG for the detection of NCSE and NCSz
      in confused elderly. The presence of IED in the first routine EEG strongly
      suggests concomitant NCSz or NCSE. Prospective studies are required to further
      determine the role of CEEG monitoring in the assessment of ACS in the elderly and
      to establish the incidence of NCSz and NCSE in this setting.

PMID- 22381389
TI  - Significance of post-operative auras after temporal lobectomy: a surprising
      methodological trap.
AB  - We aimed to examine post-operative auras/simple partial seizures and the
      associated risk of seizure recurrence after temporal lobectomy. Included were 159
      patients who underwent anterior temporal lobectomy (1995-2006) at Austin Health,
      Australia. Initial analyses used Cox regression. Post-hoc, exploratory analyses
      of aura and seizure patterns were undertaken. Initial analyses indicated that
      post-operative auras were not associated with subsequent disabling seizures (HR
      0.65, 95%CI 0.4-1.1 p=0.08). However, post-hoc examination found data patterns
      that suggest that post-operative auras may have been under-reported when medical
      contact between these events was absent. These findings are relevant to current
      research, as similar methodology is commonly employed in post-operative outcome
      studies. Important implications include potential underestimation of seizure risk
      associated with auras. Carefully planned prospective studies are required to
      assess the risk associated with post-operative auras.

PMID- 22381390
TI  - Erysothrine, an alkaloid extracted from flowers of Erythrina mulungu Mart. ex
      Benth: evaluating its anticonvulsant and anxiolytic potential.
AB  - In this study, we isolated the alkaloid erysothrine from the hydroalcoholic
      extract of flowers from E. mulungu and screened for its anticonvulsant and
      anxiolytic actions based on neuroethological and neurochemical experiments. Our
      results showed that the administration of erysothrine inhibited seizures evoked
      by bicuculline, PTZ, NMDA and most remarkably, kainic acid. Also, erysothrine
      induced an increase in the number of entries but not in the time spent in the
      open arms of the EPM. However, we did not notice any alterations in the light
      dark choice or in the open-field tests. In preliminary neurochemistry tests, we
      also showed that erysothrine (0.001-10 MUg/mL) did not alter the GABA or
      glutamate synaptossomal uptake and binding. Altogether, our results describe an
      alkaloid with anticonvulsant activity and mild anxiolytic activity that might be
      considered well tolerated as it does not alter the general behavior of the
      animals in the used doses.

PMID- 22381391
TI  - What is the right dose of lacosamide in pediatric patients with intractable
      epilepsy?

PMID- 22381392
TI  - Efficacy of safety signals in the epilepsy monitoring unit (EMU): should we
      worry?
AB  - There is little consensus regarding the critical safety measures to prevent harm
      in epilepsy monitoring units (EMUs). We sought to determine whether the safety
      signals (SS) triggered during EMU events differed by seizure type and the
      efficacy of SS in alerting responders. We screened 468 consecutive EMU admissions
      from January 2008 until April 2011 for definitive events to evaluate the first 50
      events of complex partial seizures (CPS), generalized tonic-clonic seizures
      (GTC), and psychogenic non-epileptic seizures (PNES). Response to telemetry
      signal was slower than to push button (PB). When there was PB alarm, response
      time was slower in patients with PNES. A higher proportion of PNES were triggered
      by PB. A greater percentage of epileptic seizures were missed compared with PNES.
      Future studies investigating more effective techniques to capture every epileptic
      seizure are warranted as 24/7 monitoring by healthcare professionals is not
      feasible in many settings.

PMID- 22381393
TI  - Dentists' knowledge, attitudes and practices toward patients with epilepsy in
      Hyderabad city, India.
AB  - AIM: The present study was designed to assess the knowledge, attitudes and
      practices about epilepsy among a group of dentists in Hyderabad city, India.
      MATERIALS AND METHODS: All dentists registered with the local Dental Association
      branch were eligible to participate in this questionnaire study. Descriptive and
      Inferential Statistics were used. Multiple group analysis was done using Kruskal
      Wallis, and Mann Whitney U Test was used for two-group comparison. The variables
      were taken as significant at a p value of 0.05. RESULTS: A total of 217
      respondents with mean age of 33.16+/-10.4 years participated in the study. Most
      respondents possessed a post-graduate (Master of Dental Surgery - MDS) degree
      (59.4%). A convulsion or shaking was identified as the most familiar recognizable
      symptom of epilepsy. 84.3% of the dentists would not object to their children
      having association with patients with epilepsy, and 61.3% would not object to
      their relative marrying a person with a history of epilepsy. A large number of
      dentists (178; 82%) were confident to treat a person with epilepsy. 95.3% assumed
      that they have an ethical responsibility to treat this population. None of the
      practice-related questions showed any significant difference with respect to
      different age groups, gender or the education levels (BDS/MDS). CONCLUSION: Our
      study reflects that this group of Indian dentists has a fairly high knowledge and
      positive attitudes toward patients with epilepsy. This encouraging approach and
      confidence among dentists may positively influence patients with epilepsy to seek
      dental care.

PMID- 22381394
TI  - Clinical reasoning and investigations for resective surgery for medically
      refractory epilepsies in children.
AB  - The article presents results of a UK survey of pediatric neurologists' views
      regarding resective surgery for medically refractory epilepsies in children. In
      contrast to surveys with adult neurologists, the findings indicate that delays to
      surgery in the pediatric field are not likely to be due to clinicians' views.
      There is, however, variability in clinicians' opinions as to what constitutes
      medically refractory epilepsy, variability in the factors reported as necessary
      for surgery eligibility, and uncertainty as to how these concepts should be
      defined. The survey highlights the need for elucidation of the epilepsy surgery
      process for pediatric patients, clear communication between epilepsy surgery
      centers and referring neurologists, and dissemination of consensus guidelines
      relating to the criteria for both medically refractory epilepsy and surgery
      eligibility.

PMID- 22381395
TI  - A new approach to scaffold fixation by magnetic forces: Application to large
      osteochondral defects.
AB  - Scaffold fixation represents one of the most serious challenges in osteochondral
      defect surgery. Indeed, the fixation should firmly hold the scaffold in the
      implanted position as well as it should guaranty stable bone/scaffold interface
      for efficient tissue regeneration. Nonetheless successful results have been
      achieved for small defect repair, the fixation remains really problematic for
      large defects, i.e. defects with areas exceeding 2cm(2). This paper advances an
      innovative magnetic fixation approach based on application of magnetic scaffolds.
      Finite element modeling was exploited to investigate the fixation efficiency. We
      considered three magnetic configurations: (1) external permanent magnet ring
      placed around the leg near the joint; (2) four small permanent magnet pins
      implanted in the bone underlying the scaffold; (3) four similarly implanted
      stainless steel pins which magnetization was induced by the external magnet. It
      was found that for most appropriate magnetic materials and optimized magnet
      scaffold positioning all the considered configurations provide a sufficient
      scaffold fixation. In addition to fixation, we analyzed the pressure induced by
      magnetic forces at the bone/scaffold interface. Such pressure is known to
      influence significantly the bone regeneration and could be used for magneto
      mechanical stimulation.

PMID- 22381396
TI  - New perspectives on the dynamic behaviour of oral lichen planus.
AB  - Lichen planus, a chronic inflammatory disease that affects the skin and mucous
      membranes, is one of the most frequent dermatological disorders of the oral
      cavity. The prevalence of oral lichen planus ranges from 0.2% to 4%. The
      triggering factors remain unknown. Oral lichen planus can be considered to be a
      chronic disease of long duration with a dynamic evolution and frequent changes in
      clinical appearance. Three successive active stages can be distinguished, without
      sharp limits between them: an initial stage; a protracted intermediate stage with
      alternate periods of variable activity and quiescence, which carries a
      progressively increasing risk of malignant transformation; and a late stage that
      often ends in a clinically little-known, inactive cicatricial post-lichen stage,
      which does not respond to steroid treatment but retains the same risk.

PMID- 22381397
TI  - Longitudinal evaluation of microvessel density in survivors vs. nonsurvivors of
      cardiac pathologic antibody-mediated rejection.
AB  - BACKGROUND: Antibody-mediated rejection (AMR) of cardiac allografts is associated
      with reduced long-term graft survival, but not every patient with AMR develops
      premature graft failure. The tissue level mechanisms leading to graft failure in
      some patients with antibody-mediated rejection are poorly characterized. METHODS:
      We assessed changes in myocardial microvessel density (number of capillaries per
      unit area) in endomyocardial biopsies over time using whole-slide microscopic
      imaging of CD34-stained slides and computer-assisted image analysis. Changes were
      compared among eight heart transplant recipients with multiple episodes of
      pathologic AMR who died from cardiovascular causes, eight age- and gender-matched
      patients with pathologic AMR who were still alive at a similar follow-up
      interval, and six matched controls without AMR or cellular rejection. RESULTS:
      Microvessel density decreased in the last biopsies (mean 6.52 years post
      transplant) from patients with pathologic AMR and cardiovascular mortality
      compared to their biopsies at 6 and 12 months post-transplant [respectively, -22%
      (P=.02) and -25% (P=.02)]. A similar decrease was not seen for the other groups.
      CONCLUSIONS: Significantly reduced myocardial microvessel density does occur in a
      subset of patients with pathologic AMR who have a worse outcome. These data
      provide insights into the interplay between AMR, microvascular injury, and
      clinical outcomes.

PMID- 22381398
TI  - Nicotine modifies in vivo and in vitro rat hippocampal amyloid precursor protein
      processing in young but not old rats.
AB  - Previous studies have shown that administration of nicotine modifies the
      expression and secretion of amyloid precursor protein (APP) in various cell
      lines. The present study investigated the extent to which chronic subcutaneous
      nicotine administration influences APP levels and processing in cerebral cortex,
      striatum and hippocampus of young and old rat brains. The results showed that
      constant nicotine infusion (0.25 or 4.00mg/kg/day) increased the levels of
      particulate APP (APPp) but not secreted APP (APPs) in the hippocampus of young
      rats in vivo. This response to nicotine was not observed in the striatum or
      cerebral cortex of young rats or in any of the brain regions examined in old
      animals. Subsequent in vitro analysis demonstrated that nicotine enhanced the
      release of APPs from hippocampal slice preparations and that this increase was
      attenuated by mecamylamine, a non-selective nicotinic acetylcholine receptor
      (nAChR) antagonist. The in vitro effect of nicotine on APPs was age-related,
      being only detected from hippocampal slices derived from the young but not the
      older animals. These results suggest that nicotine modulates APP expression and
      secretion in the hippocampus and that the responses observed to the drug are age
      dependent being only detected in younger rats.

PMID- 22381399
TI  - Lack of association between rs597668 polymorphism near EXOC3L2 and late-onset
      Alzheimer's disease in Han Chinese.
AB  - Recently, an international genome-wide association study (GWAS) additionally
      found rs597668 near EXOC3L2/BLOC1S3/MARK4 was a new genome-wide significance
      locus associated with late-onset Alzheimer's disease (LOAD) in Caucasians. Follow
      up replication studies were conducted almost exclusively in Caucasians, and the
      effects of the risk locus in other populations are as yet unknown. This study
      investigated the GWAS-associated locus near EXOC3L2 in 1205 unrelated Northern
      Han Chinese subjects comprising 598 LOAD patients and 607 healthy controls
      matched for gender and age. The results showed no significant differences in the
      genotypic or allelic distributions of rs597668 polymorphism between LOAD cases
      and healthy controls (genotype: P=0.653; allele: P=0.603), even after
      stratification for apolipoprotein E (APOE) E4 status and statistical adjustment
      for age, gender and APOE E4 status. This study suggests that the rs597668
      polymorphism near EXOC3L2 may not play a major role in the susceptibility to LOAD
      in the Northern Han Chinese population.

PMID- 22381400
TI  - Potential protection of green tea polyphenols against intracellular amyloid beta
      induced toxicity on primary cultured prefrontal cortical neurons of rats.
AB  - The present study was performed to explore the effect of green tea polyphenols on
      the intracellular Abeta (iAbeta)-induced toxicity to cultured rat primary
      prefrontal cortical neurons. Administration of 100nM, 1MUM or 10MUM of green tea
      polyphenols significantly inhibited the iAbeta-induced toxicity to cultured rat
      primary prefrontal cortical neurons tested by MTT and LDH release assays. We
      further studied the involvement of neuroprotective pathway protein AKT in green
      tea polyphenols protection against iAbeta-induced cytotoxicity on cultured rat
      primary prefrontal cortical neurons. The results demonstrated that the content of
      p-AKT decreased significantly after iAbeta treatment, while administration of
      green tea polyphenols significantly inhibited the iAbeta-induced decrease in the
      content of p-AKT. Moreover, blockade of AKT signalling inhibited the protective
      effects of green tea polyphenols against iAbeta-induced neurotoxicity. The
      results suggest that green tea polyphenols may play a protective effect on
      cultured rat primary prefrontal cortical neurons against iAbeta-induced
      cytotoxicity and AKT is involved in the green tea polyphenols-induced protective
      effects.

PMID- 22381401
TI  - Association between apolipoprotein E gene polymorphism and the risk of vascular
      dementia: a meta-analysis.
AB  - It remains controversial regarding the association between Apolipoprotein E
      (ApoE) gene polymorphism and the risk of vascular dementia (VaD). The present
      meta-analysis was performed to derive a more precise estimation of the
      relationship. The meta-analysis was performed by searching PubMed, Embase and Web
      of Science databases. A total of 29 studies included 1763 VaD cases and 4534
      controls were identified. The results showed evidence for significant association
      between ApoE E4 mutation and VaD risk (for E3/E4 vs. E3/E3: OR=1.65, 95% CI=1.40
      1.94, p-value<0.00001; for E4/E4 vs. E3/E3: OR=3.17, 95% CI=2.09-4.80, p
      value<0.00001; for E4 allele vs. E3 allele: OR=1.72, 95% CI=1.40-2.12, p
      value<0.00001). The similar results were obtained in the subgroup analysis based
      on ethnicity. In summary, the present meta-analysis suggests an association
      between ApoE E4 mutation and increased risk of VaD. However, due to the small
      sample size in most of the included studies and the selection bias existed in
      some studies, the results should be interpreted with caution.

PMID- 22381402
TI  - The contribution of the inferior parietal cortex to spoken language production.
AB  - This functional MRI study investigated the involvement of the left inferior
      parietal cortex (IPC) in spoken language production (Speech). Its role has been
      apparent in some studies but not others, and is not convincingly supported by
      clinical studies as they rarely include cases with lesions confined to the
      parietal lobe. We compared Speech with non-communicative repetitive tongue
      movements (Tongue). The data were analyzed with both univariate contrasts between
      conditions and probabilistic independent component analysis (ICA). The former
      indicated decreased activity of left IPC during Speech relative to Tongue.
      However, the ICA revealed a Speech component in which there was correlated
      activity between left IPC, frontal and temporal cortices known to be involved in
      language. Therefore, although net synaptic activity throughout the left IPC may
      not increase above baseline conditions during Speech, one or more local systems
      within this region are involved, evidenced by the correlated activity with other
      language regions.

PMID- 22381403
TI  - Effects of SGLT2 inhibitors on cardiovascular outcomes.
AB  - Glucose in the glomerular ultrafiltrate is actively reabsorbed by sodium glucose
      transporters (SGLT) in the proximal tubule. The SGLT2 protein is a high capacity
      molecule responsible for the majority of glucose reuptake with pharmacological
      inhibition, resulting in the loss of about 80g of glucose in the urine each day.
      About a dozen inhibitors of SGLT2 have entered clinical development, and the
      first has recently been submitted for registration with the United States Food
      and Drug Administration. The rationale for the clinical evaluation of these
      agents is their beneficial effects on glycaemia, blood pressure and body weight.
      No adequately powered trial has yet determined the effects of an SGLT2 inhibitor
      on either macrovascular or microvascular outcomes, although a number of large
      scale trials are now ongoing. Evidence that will define the overall balance of
      benefits and risks of this new drug class is anticipated within the next 5 years.

PMID- 22381404
TI  - The effect of alcohol availability on marijuana use: evidence from the minimum
      legal drinking age.
AB  - This paper exploits the discontinuity created by the minimum legal drinking age
      of 21 years to estimate the causal effect of increased alcohol availability on
      marijuana use. We find that consumption of marijuana decreases sharply at age 21,
      while consumption of alcohol increases, suggesting that marijuana and alcohol are
      substitutes. We further find that the substitution effect between alcohol and
      marijuana is stronger for women than for men. Our results suggest that policies
      designed to limit alcohol use have the unintended consequence of increasing
      marijuana use.

PMID- 22381405
TI  - The effects of the stress response on immune function in invertebrates: an
      evolutionary perspective on an ancient connection.
AB  - Stress-induced changes in immune function occur in animals across phyla, and
      these effects are usually immunosuppressive. The function of this
      immunomodulation remains elusive; however, the existence of specialized receptors
      on immune cells suggests that it is adaptive. A comparative approach may provide
      a useful perspective. Although invertebrates have simpler
      endocrine/neuroendocrine systems and immune systems than vertebrates, they have
      robust stress responses that include the release of stress
      hormones/neurohormones. Stress hormones modify immune function in mollusks,
      insects, and crustaceans. As in vertebrates, the effects of stress
      hormones/neurohormones on invertebrate immune function are complex, and are not
      always immunosuppressive. They are context-, stressor-, time- and concentration
      dependent. Stress hormone effects on invertebrate immune function may help to re
      align resources during fight-or-flight behavior. The data are consistent with the
      hypothesis that stress hormones induce a reconfiguration of networks at
      molecular, cellular and physiological levels that allow the animal to maintain
      optimal immunity as the internal environment changes. This reconfiguration
      enhances some immune functions while suppressing others. Knowing the molecular
      details of these shifts will be critical for understanding the adaptive function
      of stress hormones on immune function.

PMID- 22381406
TI  - New tools for ubiquitin signaling.

PMID- 22381407
TI  - Identical binding sites--nonidentical functions in Eukarya and Archaea: the
      complex of aeIF6 with the large ribosomal subunit.

PMID- 22381408
TI  - Disordered competitive recruiter: fast and foldable.

PMID- 22381409
TI  - Structural and functional dynamics of an integral membrane protein complex
      modulated by lipid headgroup charge.
AB  - We have used membrane surface charge to modulate the structural dynamics of an
      integral membrane protein, phospholamban (PLB), and thereby its functional
      inhibition of the sarcoplasmic reticulum Ca-ATPase (SERCA). It was previously
      shown by electron paramagnetic resonance, in vesicles of neutral lipids, that the
      PLB cytoplasmic domain is in equilibrium between an ordered T state and a
      dynamically disordered R state and that phosphorylation of PLB increases the R
      state and relieves SERCA inhibition, suggesting that R is less inhibitory. Here,
      we sought to control the T/R equilibrium by an alternative means-varying the
      lipid headgroup charge, thus perturbing the electrostatic interaction of PLB's
      cationic cytoplasmic domain with the membrane surface. We resolved the T and R
      states not only by electron paramagnetic resonance in the absence of SERCA but
      also by time-resolved fluorescence resonance energy transfer from SERCA to PLB,
      thus probing directly the SERCA-PLB complex. Compared to neutral lipids, anionic
      lipids increased both the T population and SERCA inhibition, while cationic
      lipids had the opposite effects. In contrast to conventional models, decreased
      inhibition was not accompanied by decreased binding. We conclude that PLB binds
      to SERCA in two distinct structural states of the cytoplasmic domain: an
      inhibitory T state that interacts strongly with the membrane surface and a less
      inhibitory R state that interacts more strongly with the anionic SERCA
      cytoplasmic domain. Modulating membrane surface charge provides an effective way
      of investigating the correlation between structural dynamics and function of
      integral membrane proteins.

PMID- 22381412
TI  - Deep vein thrombosis and pulmonary embolism in patients undergoing total hip
      arthroplasty: the promise of new oral anticoagulants.
AB  - Although effective agents exist for thromboprophylaxis to decrease risk of venous
      thromboembolism, particularly following major orthopaedic surgery, including
      total hip arthroplasty, these agents are underused, and thromboembolic events
      continue to occur in patients undergoing these surgical procedures. One reason
      for suboptimal treatment may be concern about bleeding; another may be
      dissatisfaction with currently available prophylactic agents. New oral
      anticoagulants appear to be equally efficacious and will provide easier
      administration and management. They hold promise for improving utilization of
      thromboprophylaxis and consequently for reducing the incidence of venous
      thromboembolism.

PMID- 22381410
TI  - ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable
      malignant gastrointestinal stromal tumor: monitoring with 18F-FDG PET and
      correlation with genotype and GLUT4 expression.
AB  - We investigated the correlation between metabolic response by (18)F-FDG PET and
      objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA
      mutation status in patients with gastrointestinal stromal tumor undergoing
      neoadjuvant imatinib mesylate therapy. METHODS: (18)F-FDG PET was performed at
      baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective
      response was defined by version 1.0 of the Response Evaluation Criteria in Solid
      Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by
      immunohistochemistry were done on tissue obtained at baseline or surgery.
      RESULTS: (18)F-FDG PET showed high baseline tumor glycolytic activity (mean
      SUV(max), 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate
      (mean, 5.5; range, -0.5-47.7, P < 0.001, n = 44), and again before surgery (mean,
      3.0; range, -0.5-36.1, P < 0.001, n = 40). At week 1, there were 3 patients with
      complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6
      with stable metabolic disease (SMD), and 2 with progressive metabolic disease
      (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none
      with PMD. The best response according to RECIST was 2 with partial response, 36
      with stable disease, and 1 with progressive disease (n = 39). Of the patients
      with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had
      SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had
      PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1
      had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22
      had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a
      wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR,
      and 1 had SMD before surgery. CONCLUSION: After imatinib mesylate initiation,
      metabolic response by (18)F-FDG PET was documented earlier (1-7 d) and was of
      much greater magnitude (36/44) than that documented by RECIST (2/39).
      Immunohistochemistry data suggest that GLUT4 may play a role in (18)F-FDG uptake
      in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate
      therapy in most patients with PMR, and the biologic action of imatinib mesylate
      interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic
      response was observed as early as days 1-7 in patients with exon 11 mutations.

PMID- 22381413
TI  - Spinous process wiring versus lateral mass fixation for the treatment of anterior
      cervical pseudarthrosis: a biomechanical comparison.
AB  - Our objective was to compare the stiffness of lateral mass screws versus two
      different spinous process wiring constructs in a cadaveric model of plated
      anterior cervical pseudoarthrosis. When treating an anterior plated
      pseudoarthrosis via a posterior approach, it is unclear whether the added
      expense, muscle exposure, and risk of lateral mass fixation are justified
      biomechanically versus a simpler, cheaper, and potentially less morbid wiring
      technique, because the presence of the anterior plate likely reduces motion over
      the unplated situation. Seven cadaveric cervical spines were loaded in
      compression, flexion, extension, lateral bending, and torsion. Each load sequence
      was applied to: 1) the intact spine; 2) after application of a plated ACDF
      construct (pACDF); and 3) after the insertion of lateral mass (LM) screws,
      ''modified'' triple wiring (TW), or Roger's wiring (RW), in alternating order for
      each specimen. For each sequence, load deformation curves and stiffness were
      obtained. Supplemental LM fixation significantly (p <= 0.05) increased stiffness
      versus pACDF in all six modes tested. TW significantly increased stiffness versus
      pACDF in compression, flexion, and torsion, but not in extension, or lateral
      bending. RW significantly increased stiffness versus pACDF only in axial torsion.
      When comparing LM to the wiring constructs, LM fixation was significantly stiffer
      than RW in flexion, extension, and lateral bending; LM fixation was stiffer than
      TW in lateral bending. LM fixation produced the stiffest overall constructs in
      stabilizing a plated pseudarthrosis ACDF model. It was significantly stiffer in
      more modes versus RW than TW.

PMID- 22381414
TI  - Effects of supplemental oxygen and hyperbaric oxygen on tendon healing in a rat
      model.
AB  - Systemic supplemental oxygen therapy (SOT) and hyperbaric oxygen therapy (HBOT)
      have been shown to positively impact wound healing. The purpose of this study was
      to evaluate the effects of SOT and HBOT on tendon healing in a rat tendon model.
      The right patellar tendon of 90 male Sprague-Dawley rats was completely
      sectioned. Animals were randomized to receive HBOT, SOT, or room air therapy.
      Animals were sacrificed at 3- and 6-weeks postoperatively. The ultimate tensile
      strength in axial extension was compared between groups. Statistical significance
      was calculated using the Student's t-test. The SOT group exhibited the highest
      tensile strength at both time-points, although HBOT was the only treatment that
      exhibited a statistically significant increase in tensile strength between time
      periods (p = 0.006). There was no statistical difference in ultimate tensile
      strength when the three groups were compared at the 3- or 6-week time-points.
      Results presented here cannot support the premise that intermittent HBOT or SOT
      significantly increases the healing of tendon repairs.

PMID- 22381415
TI  - Treatment of high-energy supracondylar/intercondylar fractures of the distal
      humerus.
AB  - Operative treatment of high-energy intra-articular fractures of the distal
      humerus is challenging and controversial. We conducted a retrospective study at a
      Level I trauma center to evaluate the results of a specific treatment protocol.
      Seventy-one patients were treated through a posterior olecranon osteotomy.
      Capsulectomy was performed in patients who perceived their functional range of
      motion to be limited after an average of 10~months. Clinical followup consisted
      of physical examination, radiography, and completion of the Disabilities of the
      Arm, Shoulder and Hand (DASH) questionnaire. Average followup duration was 22
      (range, 6 to 70) months. Sixty-five percent of the patients achieved excellent or
      good results, 28% fair, and 7% poor. Thirty-one percent underwent capsulectomy,
      with 59% of those patients achieving excellent or good results. This is the
      largest series reported to date. Our patients experienced mild functional
      impairment and a low rate of nonunion. We advocate capsulectomy for patients with
      limited range of motion postoperatively.

PMID- 22381416
TI  - Surgical reconstruction of end-stage ankle arthritis and concomitant stage II
      posterior tibial tendon insufficient flat foot.
AB  - End-stage degenerative joint disease of the ankle and concomitant ipsilateral
      Stage II posterior tibial tendon insufficient flat foot is a well known entity.
      Despite this, treatment options have not been discussed in the orthopaedic
      literature. A case series consisting of five patients was conducted to determine
      the efficacy of our treatment proposal. Our surgical treatment included an ankle
      fusion and concomitant flat foot reconstruction with a medializing calcaneal
      osteotomy, lengthening calcaneal osteotomy, and flexor digitorum longus transfer.
      At the final followup visit all patients were content with the results of the
      procedure, and would have it performed again. Each patient had significant relief
      of ankle and foot pain, and believed they had improved quality of life and
      function. Complications included two ankle nonunions treated with revision bone
      grafting and internal fixation, painful hardware and iliac crest hematoma. We
      conclude that our method of treatment is a viable option for this complex
      problem. A long recovery period should be anticipated and patients should be
      counseled accordingly.

PMID- 22381417
TI  - Case report: lead toxicity associated with an extra-articular retained missile 14
      years after injury.
AB  - Lead toxicity associated with extra-articular retained missiles (EARMs) is an
      uncommon yet potentially devastating complication of gunshot wounds. While the
      risk of lead toxicity with intra-articular retained missiles is well-known, EARMs
      are routinely permitted to remain in tissues indefinitely without surveillance
      for lead toxicity. We present a 34 year-old man who was found to have symptomatic
      lead toxicity 14 years after sustaining a gunshot-associated femoral fracture
      with retention of lead bullet fragments. A fluid-filled cyst containing two large
      lead bullet fragments was identified intraoperatively. Whole-blood lead
      concentration decreased after removal of the lead-filled cyst. Cyst formation and
      concomitant bone fracture are two of the risk factors for lead toxicity in
      patients with EARMs after gunshot wounds. Recognizing risk factors for EARM
      associated elevation in lead levels is important as the adverse effects of
      increased lead burden may be asymptomatic and difficult to diagnose, yet
      debilitating and potentially lethal.

PMID- 22381418
TI  - Use of a free-functioning muscle transfer from a paralyzed lower extremity to
      restore upper extremity elbow flexion.
AB  - This report documents the use of a free-functioning gracilis muscle transfer from
      a lower extremity paralyzed from a spinal cord injury to restore elbow flexion in
      the patient's upper extremity which was paralyzed from a brachial plexus injury.
      The transfer was performed nine months after injury and resulted in functional
      elbow flexion. Clinical examination and EMG analysis document function of the
      transferred muscle with grade 4 muscle strength. The resultant effect on the
      skeletal muscle is different after upper motor neuron injury versus lower motor
      neuron injury. The successful function of a free-functioning muscle transfer
      after a spinal cord injury in this case has important implications for patients
      with spinal cord injury.

PMID- 22381419
TI  - Traumatic laceration of the long head of the biceps brachii from a displaced
      surgical neck fracture of the humerus: case report.
AB  - This case report identifies a traumatic laceration of the long head of the biceps
      brachii associated with a displaced surgical neck fracture of the humerus in a 37
      year-old woman who sustained a fall while skiing. At the time of surgery, the
      tendon was found sharply divided and repaired primarily. The fracture was fixed
      with a proximal humeral blade plate. Followup revealed nearly full glenohumeral
      motion and a functional biceps muscle by 4 months.

PMID- 22381420
TI  - H-Wave(r) effects on blood flow and angiogenesis in longitudinal studies in rats.
AB  - Effects of repeated H-Wave(r) device stimulation (HWDS) on blood flow and
      angiogenesis in the rat hind limb were studied. The hypothesis tested was that
      HWDS acutely increases hind limb blood flow, and that repeated HWDS would elicit
      angiogenesis. Animals were HWDS-conditioned (''Conditioned'') or sham-stimulated
      (''Sham'') (n = 5/group) daily for 3 weeks. The contralateral limb in both groups
      served as the control. Each animal was injected with bromodeoxyuridine (BrDU).
      After 3 weeks, rats were anesthetized and iliac artery blood flow was measured
      bilaterally before, during, and after acute HWDS. HWDS of the Conditioned limbs
      elicited a 247% increase in blood flow above resting conditions compared to a
      200% increase in control legs. Sham animals did not demonstrate between-leg
      differences in flow. Hindlimb musculature staining for BrDU revealed angiogenesis
      in Conditioned versus Sham groups. Flow changes accompanying HWDS corroborated
      earlier microvascular findings demonstrating a significant striated muscle
      arteriolar dilation with HWDS.

PMID- 22381421
TI  - Locating the global governance of HIV and AIDS: exploring the geographies of
      transnational advocacy networks.
AB  - Over the last two decades, HIV and AIDS have been framed as a "global problem".
      In the process, transnational advocacy networks have emerged as important actors,
      and particular places are recognised as key nodes in global HIV and AIDS
      governance. Using the example of London, UK, this paper examines how these
      networks are involved in local articulations of global governance and reveals
      that 'global' processes are inflected by the locations through which networks are
      routed. The example suggests the need for further analysis of the geographies
      through which HIV and AIDS is reconfiguring power relations at a variety of
      spatial scales.

PMID- 22381422
TI  - A systematic review of associations between the primary school built environment
      and childhood overweight and obesity.
AB  - This systematic review considers current literature on the association between
      childhood overweight and obesity and the primary school built environment.
      Bibliographic databases from the fields of medicine, social science, exercise
      science and education were systematically searched. The following elements of the
      built environment were found to have been investigated: playground availability
      and adequacy; gymnasium availability and adequacy; school field, showers and
      covered playground availability. One intervention study was identified which
      utilized the built environment as an adjunct to a behavior change intervention.
      This systematic review identified minimal research upon the association between
      the school built environment and weight status and the current results are
      inconclusive.

PMID- 22381423
TI  - A Ru(I) metalloradical that catalyzes nitrene coupling to azoarenes from
      arylazides.
AB  - Unusual N-N coupling of aryl azides to yield azoarenes is demonstrated by the
      Ru(I) metalloradical, [SiP(iPr)(3)]Ru(N(2)) (4) ([SiP(iPr)(3)] = (2
      iPr(2)PC(6)H(4))(3)Si(-)). The yield of the azoarene is dependent on the
      substituent on the aryl azide, and the reaction is catalytic for p-methoxy and p
      ethoxy phenyl azides, while no azoarene is observed for p-trifluoromethylphenyl
      azide. Studies aimed at probing the viability of a bimolecular coupling mechanism
      of metal imide species, as shown in the related [SiP(iPr)(3)]Fe system, have led
      to the isolation of several structurally unusual complexes including the
      ruthenium(IV) imide, 7-OMe, as well as the Ru(II) azide adduct 8-OMe. One
      electron reduction of 7-OMe complex led to the isolation of the formally Ru(III)
      imide complex, [SiP(iPr)(3)]Ru(NAr) (Ar = p-MeOC(6)H(4), 5-OMe). EPR spectroscopy
      on 5-OMe suggests that the complex is electronically similar to the previously
      reported imide complex, [SiP(iPr)(3)]Ru(NAr) (Ar = p-CF(3)C(6)H(4,)5-CF(3)), and
      features radical character on the NAr moiety, but to a greater degree. The
      stability of 5-OMe establishes that bimolecular coupling of 5-OMe is kinetically
      inconsistent with the reaction. Further studies rule out mechanisms in which 5
      OMe reacts directly with free aryl azide or a transient Ru(I) azide adduct.
      Together, these studies show that 5-OMe is likely uninvolved in the catalytic
      cycle and demonstrates the influence of the metal center on the mechanism of
      reaction. Instead, we favor a mechanism in which free aryl nitrene is released
      during the catalytic cycle and combines with itself or with free aryl azide to
      yield the azoarene.

PMID- 22381424
TI  - Platelet biology and response to antiplatelet therapy in women: implications for
      the development and use of antiplatelet pharmacotherapies for cardiovascular
      disease.
AB  - Women are underrepresented in cardiovascular studies, even as their preponderance
      in the aging population steadily increases. Although concerns have been raised
      about the differential benefit of antiplatelet medications for women, the
      propensity for increased bleeding among women has also been recognized. A better
      understanding of the factors contributing to the observed sex-related differences
      in platelet biology is warranted. These factors include differences in the
      frequency and expression of genetic polymorphisms affecting platelet
      responsiveness to agonists (with and without antiplatelet therapies), which might
      be obtained through population-based studies and in large controlled clinical
      trials; inflammatory marker levels and their influence on atherothrombotic risk,
      and the role of specific hormones in mediating platelet activation and function.
      Knowledge gained about these mechanistic factors might inform the development of
      sex-specific antithrombotic treatment regimens that confer optimized safety and
      efficacy.

PMID- 22381425
TI  - Renal sympathetic denervation reduces left ventricular hypertrophy and improves
      cardiac function in patients with resistant hypertension.
AB  - OBJECTIVES: This study investigated the effect of catheter-based renal
      sympathetic denervation (RD) on left ventricular hypertrophy (LVH) and systolic
      and diastolic function in patients with resistant hypertension. BACKGROUND: LVH
      and diastolic dysfunction are associated with elevated sympathetic activity and
      increased morbidity and mortality. The effect of RD on LVH and LV function is
      unclear. METHODS: Forty-six patients underwent bilateral RD, and 18 patients
      served as controls. Transthoracic echocardiography was performed at baseline, and
      after 1 month and 6 months. RESULTS: Besides reduction of systolic and diastolic
      blood pressure (-22.5/-7.2 mm Hg at 1 month and -27.8/-8.8 mm Hg at 6 months, p <
      0.001 at each time point), RD significantly reduced mean interventricular septum
      thickness from 14.1 +/- 1.9 mm to 13.4 +/- 2.1 mm and 12.5 +/- 1.4 mm (p =
      0.007), and LV mass index from 53.9 +/- 15.6 g/m(2.7) (112.4 +/- 33.9 g/m(2)) to
      47.0 +/- 14.2 g/m(2.7) (103.6 +/- 30.5 g/m(2)) and 44.7 +/- 14.9 g/m(2.7) (94.9
      +/- 29.8 g/m(2)) (p < 0.001) at 1 month and 6 months, respectively. The mitral
      valve lateral E/E' decreased after RD from 9.9 +/- 4.0 to 7.9 +/- 2.2 at 1 month
      and 7.4 +/- 2.7 at 6 months (p < 0.001), indicating reduction of LV filling
      pressures. Isovolumic relaxation time shortened (baseline 109.1 +/- 21.7 ms vs.
      85.6 +/- 24.4 ms at 6 months, p = 0.006), whereas ejection fraction significantly
      increased after RD (baseline: 63.1 +/- 8.1% vs. 70.1 +/- 11.5% at 6 months, p <
      0.001). No significant changes were obtained in control patients. CONCLUSIONS:
      Besides the known effect on blood pressure, our study showed for the first time
      that RD significantly reduces LV mass and improves diastolic function, which
      might have important prognostic implications in patients with resistant
      hypertension at high cardiovascular risk.

PMID- 22381426
TI  - Effects of autonomic modulation: more than just blood pressure.

PMID- 22381427
TI  - Additional use of trimetazidine in patients with chronic heart failure: a meta
      analysis.
AB  - OBJECTIVES: The aim of this meta-analysis was to evaluate the effects of
      additional trimetazidine (TMZ) treatment on patients with chronic heart failure
      (CHF). BACKGROUND: Conflicting results currently exist on the clinical use of TMZ
      in CHF patients. METHODS: PubMed, MEDLINE, EMBASE, and EBM Reviews databases were
      searched through November 2010 for randomized controlled trials (RCTs) assessing
      TMZ treatment in CHF patients. Data concerning the study design, patient
      characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean
      differences (WMD) were calculated using fixed or random effects models. RESULTS:
      Sixteen RCTs involving 884 CHF patients were included. Hospitalization for
      cardiac causes (RR: 0.43, p = 0.03), but not all-cause mortality (RR: 0.47, p =
      0.27), was reduced by TMZ treatment. Moreover, TMZ therapy was associated not
      only with the increase of left ventricular ejection fraction (WMD: 6.46%, p <
      0.0001) and total exercise time (WMD: 63.75 seconds, p < 0.0001), but also with
      the decrease of New York Heart Association functional class (WMD: -0.57, p =
      0.0003), left ventricular end-systolic diameter (WMD: -6.67 mm, p < 0.0001), left
      ventricular end-diastolic diameter (WMD: -6.05 mm, p < 0.0001), and B-type
      natriuretic peptide (WMD: -203.40 pg/ml, p = 0.0002). CONCLUSIONS: Additional use
      of TMZ in CHF patients may decrease hospitalization for cardiac causes, improve
      clinical symptoms and cardiac function, and simultaneously ameliorate left
      ventricular remodeling.

PMID- 22381428
TI  - The clinical impact of incomplete left atrial appendage closure with the Watchman
      Device in patients with atrial fibrillation: a PROTECT AF (Percutaneous Closure
      of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in
      Patients With Atrial Fibrillation) substudy.
AB  - OBJECTIVES: The purpose of this study was to investigate the frequency and
      clinical impact of incomplete left atrial appendage (LAA) sealing and consequent
      peri-device residual blood flow in patients undergoing percutaneous LAA closure
      with the Watchman device (Atritech, Inc., Plymouth, Minnesota). BACKGROUND:
      During percutaneous LAA closure for stroke prophylaxis, the geometric variability
      of the LAA ostium may result in an incomplete seal of the LAA. On the one hand,
      this could enhance thrombus formation and embolization of thrombi around the
      device into the circulation; on the other hand, the relatively small size of
      these leaks may preclude clinically relevant embolizations. METHODS: Patients
      randomly assigned to device implantation in the PROTECT AF (Percutaneous Closure
      of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in
      Patients With Atrial Fibrillation) trial were analyzed. Transesophageal
      echocardiography was performed at 45 days, 6 months, and 12 months. Per the study
      protocol, patients discontinued warfarin therapy if the 45-day Transesophageal
      echocardiogram revealed either minimal or no peri-device flow (jet <=5 mm width).
      The impact of peri-device flow severity, defined as minor, moderate, or major (<1
      mm, 1 mm to 3 mm, >3 mm, respectively) on the composite primary efficacy endpoint
      (stroke, systemic embolism, and cardiovascular death) is expressed as hazard
      ratio (HR) with 95% confidence interval (CI). RESULTS: Transesophageal
      echocardiography follow-up revealed that 32.0% of implanted patients had at least
      some degree of peri-device flow at 12 months. The HR of the primary efficacy
      endpoint per 1 mm larger per-device flow was 0.84 (95% CI: 0.62 to 1.14; p =
      0.256). Compared to patients with no peri-device flow, the HRs were 0.85 (95% CI:
      0.11 to 6.40), 0.83 (95% CI: 0.33 to 2.09), and 0.48 (95% CI: 0.11 to 2.09) for
      minor, moderate, and major peri-device flow, respectively (p = 0.798). Compared
      to patients with no peri-device flow who discontinued warfarin, the HR for
      patients with any peri-device flow and continuing warfarin was 0.63 (95% CI: 0.14
      to 2.71; p = 0.530). CONCLUSIONS: These data indicate that residual peri-device
      flow into the LAA after percutaneous closure with the Watchman device was common,
      and is not associated with an increased risk of thromboembolism. This finding
      should be interpreted with caution as the low event rate decreases the confidence
      of this conclusion.

PMID- 22381429
TI  - Histopathologic characterization of chronic radiofrequency ablation lesions for
      pulmonary vein isolation.
AB  - OBJECTIVES: This study describes the histopathologic and electrophysiological
      findings in patients with recurrence of atrial fibrillation (AF) after pulmonary
      vein (PV) isolation who underwent a subsequent surgical maze procedure.
      BACKGROUND: The recovery of PV conduction is commonly responsible for recurrence
      of AF after catheter-based PV isolation. METHODS: Twelve patients with recurrent
      AF after acutely successful catheter-based antral PV isolation underwent a
      surgical maze procedure. Full-thickness surgical biopsy specimens were obtained
      from the PV antrum in areas of visible endocardial scar. Before biopsy,
      intraoperative epicardial electrophysiological recordings were taken from each PV
      using a circular mapping catheter. RESULTS: Twenty-two PVs were biopsied from the
      12 patients 8 +/- 11 months after ablation. Eleven of the 22 specimens (50%)
      revealed transmural scar, and 11 (50%) showed viable myocardium with or without
      scar. Each biopsy specimen demonstrated evidence of injury, most commonly
      endocardial thickening (n = 21 [95%]) and fibrous scar (n = 18 [82%]). Seven of
      the 22 specimens (32%) showed conduction block at surgery. Transmural scar was
      more likely to be seen in the biopsy specimens from the PVs with conduction block
      than in specimens from the PVs showing reconnection. However, viable myocardium
      alone or mixed with scar was seen in 2 specimens from PVs with conduction block.
      CONCLUSIONS: PVs showing electrical reconnection after catheter-based antral
      ablation frequently reveal anatomic gaps or nontransmural lesions at the sites of
      catheter ablation. Nontransmural lesions are noted in some PVs with persistent
      conduction block, suggesting that lesion geometry may influence PV conduction.
      The histological findings show that nontransmural ablation can produce a dynamic
      cellular substrate with features of reversible injury. Delayed recovery from
      injury may explain late recurrences of AF after PV isolation.

PMID- 22381430
TI  - The anatomical basis of pulmonary vein reconnection after ablation for atrial
      fibrillation: wounds that never felt a scar?

PMID- 22381431
TI  - Direct comparison of different stem cell types and subpopulations reveals
      superior paracrine potency and myocardial repair efficacy with cardiosphere
      derived cells.
AB  - OBJECTIVES: The goal of this study was to conduct a direct head-to-head
      comparison of different stem cell types in vitro for various assays of potency
      and in vivo for functional myocardial repair in the same mouse model of
      myocardial infarction. BACKGROUND: Adult stem cells of diverse origins (e.g.,
      bone marrow, fat, heart) and antigenic identity have been studied for repair of
      the damaged heart, but the relative utility of the various cell types remains
      unclear. METHODS: Human cardiosphere-derived cells (CDCs), bone marrow-derived
      mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, and bone
      marrow mononuclear cells were compared. RESULTS: CDCs revealed a distinctive
      phenotype with uniform expression of CD105, partial expression of c-kit and CD90,
      and negligible expression of hematopoietic markers. In vitro, CDCs showed the
      greatest myogenic differentiation potency, highest angiogenic potential, and
      relatively high production of various angiogenic and antiapoptotic-secreted
      factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in
      superior improvement of cardiac function, the highest cell engraftment and
      myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks
      after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic
      cells. The c-kit(+) subpopulation purified from CDCs produced lower levels of
      paracrine factors and inferior functional benefit when compared with unsorted
      CDCs. To validate the comparison of cells from various human donors, selected
      results were confirmed in cells of different types derived from individual rats.
      CONCLUSIONS: CDCs exhibited a balanced profile of paracrine factor production
      and, among various comparator cell types/subpopulations, provided the greatest
      functional benefit in experimental myocardial infarction.

PMID- 22381433
TI  - Neural remodeling and myocardial infarction: the stellate ganglion as a double
      agent.

PMID- 22381432
TI  - Electroanatomic remodeling of the left stellate ganglion after myocardial
      infarction.
AB  - OBJECTIVES: The purpose of this study was to evaluate the changes of left
      stellate ganglionic nerve activity (SGNA) and left thoracic vagal nerve activity
      (VNA) after acute myocardial infarction (MI). BACKGROUND: Whether MI results in
      remodeling of extracardiac nerve activity remains unclear. METHODS: We implanted
      radiotransmitters to record the SGNA, VNA, and electrocardiogram in 9 ambulatory
      dogs. After baseline monitoring, MI was created by 1-h balloon occlusion of the
      coronary arteries. The dogs were then continuously monitored for 2 months. Both
      stellate ganglia were stained for growth-associated protein 43 and synaptophysin.
      The stellate ganglia from 5 normal dogs were used as control. RESULTS: MI
      increased 24-h integrated SGNA from 7.44 +/- 7.19 Ln(Vs)/day at baseline to 8.09
      +/- 7.75 Ln(Vs)/day after the MI (p < 0.05). The 24-h integrated VNA before and
      after the MI was 5.29 +/- 5.04 Ln(Vs)/day and 5.58 +/- 5.15 Ln(Vs)/day,
      respectively (p < 0.05). A significant 24-h circadian variation was noted for the
      SGNA (p < 0.05) but not the VNA. The SGNA/VNA ratio also showed significant
      circadian variation. The nerve densities from the left SG were 63,218 +/- 34,719
      MUm(2)/mm(2) and 20,623 +/- 4,926 MUm(2)/mm(2) for growth-associated protein 43
      (p < 0.05) and were 32,116 +/- 8,190 MUm(2)/mm(2)and 16,326 +/- 4,679
      MUm(2)/mm(2) for synaptophysin (p < 0.05) in MI and control groups, respectively.
      The right SG also showed increased nerve density after MI (p < 0.05).
      CONCLUSIONS: MI results in persistent increase in the synaptic density of
      bilateral stellate ganglia and is associated with increased SGNA and VNA. There
      is a circadian variation of the SGNA/VNA ratio. These data indicate significant
      remodeling of the extracardiac autonomic nerve activity and structures after MI.

PMID- 22381434
TI  - A rare case of myocardial bridge involving left main, left circumflex, and left
      anterior descending coronary arteries.

PMID- 22381435
TI  - President's page: heroes and the shoulders of giants.

PMID- 22381436
TI  - Multimodality imaging of thrombus in transit crossing a patent foramen ovale.

PMID- 22381437
TI  - Predictors of clinical pain in fibromyalgia: examining the role of sleep.
AB  - Understanding individual differences in the variability of fibromyalgia pain can
      help elucidate etiological mechanisms and treatment targets. Past research has
      shown that spatial extent of pain, negative mood, and aftersensation (pain
      ratings taken after experimental induction of pain) accounts for 40 to 50% of the
      variance in clinical pain. Poor sleep is hypothesized to have a reciprocal
      relationship with pain, and over 75% of individuals with fibromyalgia report
      disturbed sleep. We hypothesized that measures of sleep would increase the
      predictive ability of the clinical pain model. Measures of usual pain, spatial
      extent of pain, negative mood, and pain aftersensation were taken from 74 adults
      with fibromyalgia. Objective (actigraph) and subjective (diary) measures of sleep
      duration and nightly wake time were also obtained from the participants over 14
      days. Hierarchical regression indicated that greater spatial extent (R(2) = .26),
      higher aftersensation ratings (R(2) = .06), and higher negative mood (R(2) = .04)
      accounted for 36% of the variance in clinical pain (average of 14 daily pain
      ratings). None of the sleep variables were significant predictors of clinical
      pain. Results replicate previous research and suggest that spatial extent of
      pain, pain aftersensation, and negative mood play important roles in clinical
      pain, but sleep disturbance did not aid in its prediction. PERSPECTIVE: This
      study suggests that measures of sleep duration and nightly wake time do not
      predict fibromyalgia pain at the group level. Fibromyalgia patients may benefit
      from a 3-pronged approach to pain management: reducing pain's spatial extent,
      normalization of central nervous system hypersensitivity, and psychobehavioral
      therapies for negative mood.

PMID- 22381438
TI  - Autonomic reactions in pain.

PMID- 22381439
TI  - Accuracy of multi-slice computed tomography for measurement of left ventricular
      ejection fraction compared with cardiac magnetic resonance imaging and two
      dimensional transthoracic echocardiography: a systematic review and meta
      analysis.
AB  - BACKGROUND: Multi-slice computed tomography (MSCT) allows non-invasive assessment
      of the coronary arteries and simultaneously can provide measurement of left
      ventricular ejection fraction (LVEF). The accuracy of newer MSCT generations (64
      slice or more) for assessment of LVEF compared with magnetic resonance imaging
      (MRI) and two-dimensional transthoracic echocardiography (TTE) has not been
      evaluated in a meta-analysis. PURPOSE: To evaluate, via a systematic literature
      review and meta-analysis, whether MSCT can assess LVEF with high accuracy
      compared with MRI and TTE. METHODS: Electronic databases and reference lists for
      relevant published studies were searched. Twenty-seven eligible studies provided
      mean LVEF% with its standard deviation (SD) measured by MSCT versus MRI and TTE.
      Meta-analysis of weighted mean difference (WMD) and Bland-Altman method were used
      to quantify the mean difference and agreement between MSCT compared with MRI and
      TTE. RESULTS: The results of combining 12 studies showed no significant
      difference in LVEF% between MSCT and MRI with a WMD of -0.11 (-1.48, 1.26, 95%
      CI), p=0.88. Bland-Altman analysis showed excellent agreement between MSCT and
      MRI with a bias of 0.0 (-3.7, 3.7 +/- 1.96SD) with 95% CI. The results of
      combining 15 studies showed no significant difference in LVEF between MSCT versus
      TTE measurements with a WMD of 0.19 (-1.13 to 1.50; 95% CI), p=0.87. Bland-Altman
      analysis showed excellent agreement between MSCT and TTE with a bias of 0.3 (
      4.7, 5.7 +/- 1.96SD) with 95% CI. CONCLUSION: The newer MSCT generations can
      provide accurate LVEF measurement compared to MRI and TTE. MSCT represents a
      valid technique for the combined evaluation of LVEF and coronary artery disease.

PMID- 22381440
TI  - Treatment failure after uterine artery embolization: prospective cohort study
      with multifactorial analysis of possible predictors of long-term outcome.
AB  - PURPOSE: To evaluate the impact of baseline characteristics and residual
      leiomyoma perfusion after uterine artery embolization (UAE) on clinical long-term
      outcome. MATERIALS AND METHODS: One hundred fifteen patients underwent UAE. All
      patients were divided into three groups according to achieved infarction rate
      determined on contrast-enhanced magnetic resonance imaging within 48-72 h after
      UAE (I: 100%, n=60; II: 90-99%, n=32; and III: 0-89%, n=23). Treatment failure
      and subsequent re-interventions (surgery, repeat UAE) were assessed for each
      group and compared using Cox regression analysis (CRA) with respect to the
      following baseline variables: age, uterine and dominant fibroid volume, number of
      fibroids, location of largest fibroid, and clinical symptoms. RESULTS: Long-term
      follow-up was completed after a median of 7.2 years (range 5.1-9.6) with a
      response rate of 84%. CRA revealed that patients in group III had a 22.2-fold
      higher risk (p<0.001) of treatment failure than patients in group I, whereas
      groups I and II did not differ significantly (p=0.578). For patients with
      bleeding-related symptoms only, CRA showed a 5.1-fold higher risk (p=0.025) of
      treatment failure than for patients with equally dominant bleeding- and bulk
      related symptoms. A 40.5-fold higher likelihood (p<0.001) of treatment failure
      was observed for patients in group III with bleeding-related symptoms only
      compared to those in group I with combined bleeding- and bulk-related symptoms.
      CONCLUSION: Incomplete fibroid infarction after UAE is strongly associated with
      the risk of experiencing treatment failure. Patients with bleeding-related
      complaints only face the highest likelihood of treatment failure if UAE results
      in less than 90% fibroid devascularization.

PMID- 22381441
TI  - Interventional bleeding, hematoma and scar-formation after vacuum-biopsy under
      stereotactic guidance: Mammotome((r))-system 11 g/8 g vs. ATEC((r))-system 12 g/9
      g.
AB  - PURPOSE: To evaluate prospectively the correlation of scar-formations after
      vacuum-assisted biopsy with different systems and needle-sizes and interventional
      bleeding/post-interventional hematoma. METHODS AND MATERIALS: Between 01/2008 and
      12/2009, 479 patients underwent vacuum-assisted biopsy under stereotactic
      guidance, using the Mammotome((r))-system with 11/8-gauge and ATEC((r))-system
      with 12/9-gauge, whereas in 178 cases with representative benign histology no
      surgical-biopsy after vacuum-assisted biopsy was performed and at least a 2-plane
      follow-up-mammogram after 6 month post-vacuum-assisted biopsy was available.
      Bleeding during intervention, hematoma post-intervention and scar-tissue was
      scored as minimal and moderate/severe. Statistical analysis included Chi-Square
      trend-test, p-value <0.05 was considered to be significant. RESULTS:
      Significantly more bleedings and post-interventional hematomas for 8-gauge
      Mammotome((r))-system vs. 11-gauge-Mammotome((r))-system (41.9% vs. 8.4%,
      p<0.001/35.5% vs. 16.7%, p=0.029), no significant-differences for the ATEC((r))
      systems 9-gauge vs. 12-gauge (26.9% vs. 29.7%, p=0.799/42.3% vs. 43.2%, p=0.596).
      11-gauge-Mammotome((r))-system vs. ATEC((r))-12-gauge-system revealed
      significantly less bleedings/hematomas (8.4% vs. 29.7%, p=0.015/16.7% vs. 43.2%,
      p=0.001), no significant differences for the large-systems (p=0.135/p=0.352).
      Follow-up of Mammotome((r))-11/8-gauge-system system has shown 13.1/16.1% minimal
      scar-formation and 1.2/3.2% moderate/severe scars, whereas ATEC((r))-12/9-gauge
      system has shown 10.8/3.8% minimal scar-formation and 0/11.5% moderate/severe
      scars, no significant differences. No significant difference was found when
      comparing Mammotome((r))-11/8-g-systems vs. ATEC((r))-12/9-g-systems
      (p=0.609/p=0.823). There was also no correlation between risk of scar-formation
      after occurrence of bleeding or hematoma with any examined VAB-system or any
      needle size in this study (p=0.800). CONCLUSION: Using larger needle-sizes
      significantly (Mammotome((r)))/not significant for ATEC((r))) more interventional
      bleedings and post-interventional hematomas were detected, only a tendency
      concerning scar-formation.

PMID- 22381442
TI  - Wingspan stent-assisted coiling of intracranial aneurysms with symptomatic parent
      artery stenosis: experience in 35 patients with mid-term follow-up results.
AB  - BACKGROUND: There is a potential risk of aneurysm rupture after parent artery
      revascularization because of increased blood flow. The purpose of this study is
      to assess the efficacy and safety of Wingspan stent-assisted coil embolization in
      the treatment of intracranial aneurysms with symptomatic parent artery stenosis.
      METHODS: Thirty-five consecutive patients (19 men, 16 women; age range, 48-79
      years; mean age, 60.4 years) harboring 35 unruptured wide-necked or fusiform
      intracranial aneurysms (mean size 6.8mm; range 2.5-18 mm.) with symptomatic
      parent artery stenosis (mean degree 71.1%; range 50-92%) were treated with the
      Wingspan stent-assisted coiling. Twenty-four lesions were located in the anterior
      circulation and eleven in the posterior circulation. Patients were premedicated
      with antiplatelet therapy consisting of aspirin 300 mg and clopidogrel 75 mg for
      at least 3 days before the procedure. Following pre-dilatation and stent
      placement, a coiling microcatheter entered the aneurysm through the interstices
      of the stent, and then coiling was performed. After the procedure, clopidogrel 75
      mg daily was recommended for an additional 30 days, and aspirin 100mg was
      recommended throughout follow-up. For all patients, clinical follow-up was
      conducted by clinic visitation, or telephone interview. Angiographic follow-up
      with DSA was recommended at 6 months and 1 year after the procedure. Angiography
      follow-up (mean time 10.6 months) was obtained in 31 cases (88.6%). The technical
      feasibility of the procedure, procedure-related complications, angiographic
      results, clinical outcome and follow-up angiography were evaluated. RESULTS: In
      every case, technical success was achieved. The degree of stenosis was reduced
      from 71.1% to 17.4% after balloon angioplasty and stenting. Immediate angiography
      demonstrated complete occlusion in 25 cases (71.4%), neck remnant in 7 cases
      (20.0%), and incomplete occlusion in 3 cases (8.6%). Procedure-related morbidity
      occurred in two patients (5.7%), including thromboembolism (n=1) and occlusion of
      small penetrating arteries (n=1). At follow-up (mean time 18.3 months), two
      additional cases of ischemic stroke occurred. The overall frequency of any
      stroke, intracranial hemorrhage, or death within 30 days or ipsilateral stroke
      beyond 30 days was 11.4%. No rehemorrhage of treated aneurysm occurred. At
      angiographic follow-up, four cases demonstrated >= 50% in-stent restenosis
      (12.9%), one of which was symptomatic, and two aneurysms (6.4% of the follow-up
      angiograms) demonstrated recanalization. CONCLUSION: We found that the Wingspan
      stent-assisted coil embolization was helpful in the treatment of intracranial
      aneurysms with parent artery stenosis.

PMID- 22381443
TI  - The surgical history, management, and outcomes of subaortic stenosis in adults.
AB  - BACKGROUND: Subaortic stenosis (SAS) is a curtain of tissue involving the
      subaortic region, the aortic and mitral valves, the septum, and the fibrous
      trigones. Little is known of its course or the outcomes of its surgical
      management in adults. METHODS: We reviewed our experience of the surgical
      management of SAS in adults from 1999 to 2010. We divided patients into three
      groups: (1) those presenting for first-time SAS resection (6 patients, 4 male,
      median age of 46.9 +/- 17 years, mean follow-up of 5 +/- 2.7 years); (2) those
      requiring redo resection of SAS without organic aortic valve dysfunction (8
      patients, 3 male, median age of 25.3 +/- 5 years, mean follow-up of 8 +/- 3.08
      years); and (3) those with SAS and aortic valve dysfunction (8 patients, 4 males,
      median age of 34.8 +/- 12 years, mean follow-up of 4.5 +/- 2.5 years; 5 had
      previous SAS surgery). RESULTS: Patients underwent extensive excision of the SAS,
      release of the fibrous trigones, and a septal myectomy if required. There was 1
      early death in group 2 and 1 in group 3. In group 3, 1 patient underwent the Ross
      procedure and 7 patients had mechanical valve implantation. No patient required
      permanent pacemaker implantation. Overall follow-up was 3.3 +/- 3 years (range, 6
      months to 10 years). The preoperative left ventricular outflow tract gradient
      ranged from 40 to 120 mm Hg, and the postoperative left ventricular outflow tract
      gradient ranged from 0 to 16 mm Hg. At latest follow-up, no patient in groups 1
      or 2 had greater than mild native aortic regurgitation. CONCLUSIONS: Subaortic
      stenosis resection in adults can successfully relieve left ventricular outflow
      tract obstruction, with low mortality. The complexity of SAS increases with time;
      therefore a longer duration of follow-up is needed to further validate our
      conclusions.

PMID- 22381444
TI  - Surgical reconstruction of tracheal stenosis in conjunction with congenital heart
      defects.
AB  - BACKGROUND: Surgical reconstruction is the primary method of treating airway
      obstruction in children. Tracheal stenosis is frequently associated with
      congenital heart defects, which may further complicate the overall management
      strategy. The purpose of this study was to review our experience with surgical
      reconstruction of airway obstruction in conjunction with congenital heart
      defects. METHODS: This was a retrospective review of our surgical experience with
      tracheal stenosis from February 2003 to August 2011. Twenty-seven patients were
      identified in our database. Six patients had isolated, congenital tracheal
      stenosis, and 21 had tracheal stenosis in association with congenital heart
      defects. There were two identifiable subgroups. Thirteen patients had airway
      stenoses identified concurrently with congenital heart defects and underwent
      combined repair. The second group comprised 8 patients who had previous
      correction of their congenital heart defects and experienced delayed presentation
      of tracheal (n = 6) or bronchial (n = 2) obstruction. RESULTS: The median age at
      surgery was 9 months. There were 2 postoperative deaths, both in children with
      single ventricle. The median duration of follow-up for the entire cohort of 25
      surviving patients was 4 years. None of the patients have required reoperations
      on the trachea; 5 have had minor reinterventions. CONCLUSIONS: The data
      demonstrate that tracheal obstruction is frequently found in conjunction with
      congenital heart defects. Nearly one third of our patients had delayed
      presentation of airway obstruction that was identified subsequent to previous
      congenital heart defect repair. Tracheal reconstructive techniques were effective
      regardless of the cause of the airway obstruction.

PMID- 22381445
TI  - Results of long segmental reconstruction of left anterior descending artery using
      left internal thoracic artery.
AB  - BACKGROUND: We performed long segmental reconstruction of the left anterior
      descending coronary artery (LAD) using the left internal thoracic artery (LITA)
      in patients with diffusely diseased coronary arteries. Our study investigated
      short- and long-term outcomes and angiographic results after complete
      revascularization using this technique. METHODS: Between March 1995 and March
      2001, 112 patients (mean age 63 years) underwent long segmental LAD
      reconstruction (>=2 cm) with or without endarterectomy using the LITA. Of these,
      68 patients (61%) had a history of old myocardial infarction, 44 (39%) had
      undergone prior percutaneous coronary intervention, 39 (35%) had unstable angina,
      and 11 (10%) required preoperative intraaortic balloon pumping. RESULTS: The
      majority of patients (96%) underwent operation under cardiac arrest. All patients
      underwent a complete revascularization with long segmental LAD reconstruction
      using the LITA. The average length of arteriotomy was 3.7 cm, and 43 patients
      (38%) underwent extensive (>=4 cm) LAD reconstruction. Endarterectomy was
      performed in 37 patients (33%). The early mortality rate was 1.8% (2 of 112).
      Perioperative myocardial infarction in the LAD territory was 5.4%. The 5- and 10
      year survival rates were 91% and 74%, respectively. Freedom from major adverse
      cardiac events at 10 years was 77%. Early angiography (n = 99) showed a 99%
      excellent patency rate of the LITA. Midterm (n = 61) and long-term (n = 23)
      follow-up angiography both showed 100% excellent patency rate of the LITA.
      CONCLUSIONS: Long segmental LAD reconstruction with or without endarterectomy
      using the LITA provided excellent long-term outcomes and acceptable early
      operative results, even in patients with diffusely diseased coronary arteries.

PMID- 22381446
TI  - Do tracheas grow after slide tracheoplasty?
AB  - BACKGROUND: Slide tracheoplasty has become the surgical technique of choice for
      repair of congenital tracheal stenosis. Despite the initial reluctance regarding
      the ability of this "reconstructed" trachea to grow, the reduced morbidity and
      mortality have allowed slide tracheoplasty to be widely adopted. The aim of this
      study was to evaluate tracheal growth after slide tracheoplasty. METHODS: This
      was a retrospective study. In follow-up bronchography performed 1, 6, 12, 18, and
      24 months after slide tracheoplasty, we measured the cross-sectional areas of the
      midtrachea and distal trachea at each investigation and correlated the
      measurements with the anthropomorphic factors (body weight, height, and body
      surface). RESULTS: Fourteen patients were enrolled in this study. The midtracheal
      and distal tracheal cross-sectional areas significantly increased with time (p <=
      0.0001). The average rates of midtracheal growth were 21.0 mm(2)year in the first
      6 months and 8.0 mm(2)/year in the first 2 years, and the distal trachea grew
      18.5 mm(2)/year and 8.4 mm(2)/year, respectively. Regression analysis showed that
      both the midtrachea and the distal trachea increase significantly with weight
      (r(2) = 0.257, p <= 0.0001), height (r(2) = 0.376, p <= 0.0001), and body surface
      area (r(2) = 0.315, p <= 0.0001). Balloon dilation did not significantly alter
      the tracheal growth in the first 2 years after slide tracheoplasty. CONCLUSIONS:
      Slide tracheoplasty does not inhibit tracheal growth. The reconstructed trachea
      grows faster in the first 6 months and slows in the following 18 months. There is
      a positive correlation between tracheal cross-sectional area and weight, height,
      and body surface area.

PMID- 22381447
TI  - Leaflet replacement for aortic stenosis using the 3f stentless aortic
      bioprosthesis: midterm results.
AB  - BACKGROUND: The 3f aortic bioprosthesis is a stentless valve resembling the
      native aortic valve. It has been postulated that improved hemodynamic performance
      with this prosthesis may translate into superior durability. We hereby report the
      midterm results using this valve substitute. METHODS: Fifty patients with severe
      aortic stenosis received the 3f aortic bioprosthesis between 2002 and 2004 in our
      unit. Clinical outcomes, effective orifice area, mean gradients, and ejection
      fraction were evaluated at discharge, at 6 and 12 months, and yearly thereafter.
      RESULTS: Mean follow-up was 52 +/- 10 months and was complete in 96% of surviving
      patients. Hemodynamic performance of the 3f valve was satisfactory for
      substitutes in the range of 25 mm and 27 mm; smaller valve substitutes showed
      unfavorable hemodynamic performance with mean gradients of 18 +/- 7 mm Hg for 21
      mm prosthesis, and 14 +/- 5 mm Hg for 23-mm prosthesis. Consequently, the
      regression of left ventricular hypertrophy was incomplete. Late mortality
      included 10 patients (valve-related in 1, cardiac-related in 3) for a survival of
      77% +/- 3% at 4 years. Four patients required reoperation owing to endocarditis
      in 2 and paravalvular leak in other 2. Freedom from reoperation was 93% at 4
      years. Six patients experienced 9 neurologic events, accounting for 82% freedom
      from neurologic events. CONCLUSIONS: Its unique design makes the 3f aortic
      bioprosthesis less complex to implant than conventional stentless valves, as only
      a single suture line is necessary. The hemodynamic profile and clinical
      performance of the prosthesis are inconsistent with the established stentless
      valves, especially with regard to higher incidence of neurologic complications
      seen during the follow-up.

PMID- 22381448
TI  - Outcomes for acute type A aortic dissection: effects of previous cardiac surgery.
AB  - BACKGROUND: The standard of performing emergent surgical repair for acute aortic
      dissection type A has been questioned in patients with previous cardiac surgery.
      The effects of previous cardiac surgery on the presentation and operative outcome
      of these patients is understudied. METHODS: Between 1998 and 2010, 190 patients
      were operated on for acute type A aortic dissection; there were 159 first cardiac
      operations (FCO) and 31 redo operations (REDO). Stepwise logistic regression
      analysis identified independent predictors of hospital mortality. Propensity
      score-matching yielded 31 FCOs who matched the REDOs with respect to age, sex,
      hypertension history, chronic obstructive pulmonary disease, and renal failure.
      The presentation, operative outcome, and complications were compared between the
      two groups. RESULTS: Hospital mortality rate was 16.8% (32 of 190). Regression
      analysis identified mental status change (odds ratio [OR] = 5.9), hypertension
      (OR = 4.6), concomitant coronary artery bypass grafting (OR = 3), reoperation (OR
      = 2.9), and age of 70 years or older (OR = 2.8) as predictors of hospital
      mortality. After matching there was no difference between REDO and FCO groups in
      the presenting symptoms, but REDOs had a higher incidence of aortic rupture (29%
      [9 of 31] versus 3.2% [1 of 31]; p = 0.012). Cardiac tamponade was present in
      3.2% (1 of 31) of REDOs versus 16.1% of FCOs (5 of 31; p = 0.195). Patients in
      the REDO group required more intraoperative blood transfusion, and had longer
      cardiopulmonary bypass time. Major complications occurred similarly between the
      two groups, except REDOs had worse renal function and a higher rate of sudden
      cardiac arrest (14.3% [4 of 28] versus 0; p = 0.045). CONCLUSIONS: Although
      hospital mortality is higher among REDOs, it is still lower than the reported
      mortality for medical management, and major complications occurred at a rate
      similar to that of FCOs; hence, emergent surgery remains the prudent treatment.

PMID- 22381449
TI  - Two-stage end-to-end reconstruction of long-segment tracheal defects with a
      bioabsorbable scaffold grafting technique in a canine model.
AB  - BACKGROUND: When a long segment of trachea is resected and grafted with a
      bioabsorbable scaffold, chronic contraction of the graft occurs, leading to
      substantial delayed native tracheal axial approximation. This phenomenon may
      allow for safe two-stage end-to-end tracheal reconstruction of large tracheal
      defects. We performed this trial to confirm that delayed tracheal axial
      approximation occurs in a mature animal model and to test the surgical
      feasibility of two-stage end-to-end tracheal reconstruction. METHODS: Five dogs
      (weight, 19 to 21 kg) underwent cervical tracheal resection and replacement (50
      mm) with use of a conduit of a copolymer of L-lactide and epsilon-caprolactone
      reinforced with polyglycolic acid. A silicone stent (70 mm) was placed to prevent
      graft collapse. Postoperative bronchoscopy and computed tomography were scheduled
      to assess tracheal approximation and graft absorption. Native tracheal end-to-end
      reconstructive surgical procedures were planned at 9 months, when the defect that
      had been grafted decreased to less than 25 mm in length. RESULTS: Suture-related
      granulation tissue in the airway of one dog, which prevented operation. The
      grafted area length in four animals ranged from 19 mm to 23 mm 9 months after
      operation. These animals then underwent tracheal reconstructive surgical
      procedures consisting of resection of the grafted area and end-to-end native
      tracheal reanastomosis without postoperative stent placement. All surgical
      procedures were successful, and there were no procedural deaths or postoperative
      complications after the second operation for as long as 2 months. CONCLUSIONS:
      Delayed tracheal axial approximation after bioabsorbable grafting was confirmed
      in a mature animal model and allowed two-stage end-to-end tracheal reconstruction
      of large tracheal defects.

PMID- 22381450
TI  - Extended single-patch repair of supravalvar aortic stenosis: a simple and
      effective technique.
AB  - BACKGROUND: The optimal surgical procedure for repair of supravalvar aortic
      stenosis (SVAS) remains uncertain. Proponents of multisinus repair techniques
      suggest improved outcomes compared with the single-patch technique. We evaluated
      the outcomes after an extended single-patch technique for relief of SVAS.
      METHODS: A cross-sectional retrospective analysis was performed of all SVAS
      patients who underwent repair from 1996 to 2009. Patient, procedural, and
      hospital course data were obtained through a review of the medical records. At
      follow-up, patients were evaluated for residual SVAS gradient, valvar aortic
      stenosis, aortic insufficiency, and need for reintervention. RESULTS: Twenty-two
      patients (mean age, 2.4 +/- 2.4 years) underwent repair of SVAS (discrete form,
      59%). Mean preoperative peak gradient was 77 +/- 27 mm Hg (range, 20 to 139 mm
      Hg). There were no hospital deaths. Median postoperative length of stay was 5
      days (range, 3 to 68 days). Mean follow-up was 4.1 +/- 3.5 years (range, 0.7 to
      13 years). Follow-up Doppler echocardiography revealed a peak left ventricular
      outflow tract gradient of 10 +/- 12 mm Hg (range, 0 to 41 mm Hg). No patient had
      significant valvar aortic stenosis or insufficiency. Two patients (9%) required
      catheter-based reintervention that was unrelated to the SVAS repair. CONCLUSIONS:
      This study demonstrates that a simple, extended single-patch technique for repair
      of SVAS provides excellent medium-term results. A durable reduction in gradient
      with low complication and recurrence rates can be achieved without the need for
      more complicated multisinus patch repairs.

PMID- 22381451
TI  - Outcomes after surgical management of synchronous bilateral primary lung cancers.
AB  - BACKGROUND: Distinguishing between synchronous primary lung cancers and
      metastatic disease in patients with bilateral lung masses is often difficult. The
      objective of this study is to examine outcomes associated with a strategy of
      performing staged bilateral resections in patients without N2 disease based on
      invasive mediastinal staging and without distant metastases. METHODS: Patients
      undergoing resections of bilateral synchronous primary lung cancer at our
      institution between 1997 and 2010 were reviewed. Perioperative complications were
      graded according to National Cancer Institute guidelines. Survival was estimated
      using the Kaplan-Meier method and compared using a log-rank test. End points
      included overall survival, disease-free survival, operative death, cancer
      recurrence, and postoperative complications. RESULTS: Resections of bilateral
      synchronous primary lung cancers were performed in 47 patients. Forty-five
      patients (96%) had at least a unilateral thoracoscopic approach; 28 (60%) had
      bilateral thoracoscopic approaches. The median postresection length of stay was 3
      days. Thirteen patients (28%) had a postoperative complication; only 3 (6%) were
      grade 3 or higher. There was 1 perioperative death (2%). Eleven patients received
      adjuvant therapy; only 3 patients in whom adjuvant therapy was indicated did not
      receive the recommended treatment. The overall 3-year survival was 35%. Survival
      of patients whose bilateral tumors had identical histology did not differ from
      patients whose histology was different (p = 0.57). Three-year disease-free
      survival was 24%. CONCLUSIONS: Aggressive surgical treatment of apparent
      synchronous bilateral primary lung cancer can be performed with low morbidity.
      Most patients tolerate the bilateral surgeries and adjuvant therapy. Overall
      survival is sufficiently high to support this aggressive approach.

PMID- 22381453
TI  - Light-induced vasodilation of coronary arteries and its possible clinical
      implication.
AB  - BACKGROUND: Low-level laser therapy and light-emitting diodes (LED) are
      increasingly used in phototherapy. Their therapeutic effects are at least partly
      mediated by light-induced vasodilation. The aim of this study was to determine
      the effect of different light sources on coronary arteries. METHODS: Porcine left
      coronary arteries were cut into 4-mm rings that were irradiated either by a
      semiconductor nonthermal gallium-arsenide diode laser or a noncoherent athermic
      red light source both with the same energy density up to 16 J/cm(2). After
      precontraction with 9, 11-dideoxy-11alpha, 9alpha-epoxymethano-prostaglandin
      F(2)alpha, respective relaxation responses were evaluated. The role of
      endothelium as well as intracellular pathways was investigated. RESULTS: Maximum
      vasodilation after exposure to laser was observed at 10 J/cm(2) (56.8% +/- 1.2%)
      and decreased to 43.9% +/- 2.8% at 16 J/cm(2) (p < 0.003). After adjusting
      exposure time to achieve equivalent energy densities in the LED group, vessel
      segments revealed photorelaxation of 52.9% +/- 6.5% and 47.5% +/- 0.6%,
      respectively. Vasodilations achieved by either light source were comparable at 10
      J/cm(2) (p < 0.574) and 16 J/cm(2) (p < 0.322). Furthermore, vasodilation could
      be inhibited by administration of 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger) and 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (guanocyclase inhibitor) but not with L
      nitro-arginine methyl ester or deendothelialization. CONCLUSIONS: Vessels exposed
      to either light source showed a remarkable as well as comparable photorelaxation
      at definite energy densities. This effect is mediated by an intracellular nitric
      oxide-dependent mechanism. As LED sources are of small size, simple, and
      inexpensive build-up, they may be used during routine coronary artery bypass
      surgery to ease suturing of anastomosis by target vessel vasodilation.

PMID- 22381452
TI  - Heterogeneous distribution of left ventricular contractile injury in chronic
      aortic insufficiency.
AB  - BACKGROUND: Global systolic strain has been described previously in patients with
      chronic aortic insufficiency (AI). This study explored regional differences in
      contractile injury. METHODS: Tagged magnetic resonance images of the left
      ventricle (LV) were acquired and analyzed to calculate systolic strain in 42
      patients with chronic AI. Multiparametric systolic strain analysis was applied to
      relate cardiac function in AI patients to a normal strain database (N = 60). AI
      patients were classified as having normal or poor function based on their
      results. A two-way repeated-measures analysis of variance was applied to analyze
      regional differences in injury. RESULTS: The mean and standard deviation of raw
      strain values (circumferential strain, longitudinal strain, and minimum principal
      strain angle) are presented over the entire LV in our normal strain database. Of
      the 42 patients with AI, 15 could be defined as having poor function by
      multiparametric systolic strain analysis. In AI patients with poor function,
      statistical analysis showed significant differences in injury between standard LV
      regions (F(3.69,44.33) = 3.47, p = 0.017) and levels (F(1.49,17.88) = 4.41, p =
      0.037) of the LV, whereas no significant differences were seen in the group with
      normal cardiac function. CONCLUSIONS: Patients with poor function, as defined by
      multiparametric systolic strain z scores, exhibit a consistent, heterogeneous
      pattern of contractile injury in which the septum and posterior regions at the
      base are most injured.

PMID- 22381454
TI  - A case of orbital hypertelorism with recovery of binocular vision after surgical
      treatment.
AB  - Orbital hypertelorism is defined as an abnormally wide bony interorbital
      distance. The aims of surgery are both correction of ocular dystopia and cosmetic
      reconstruction of the nasal crest. Marked improvement of visual function,
      especially binocular vision, by surgery is not expected. Here we report that
      surgical treatment unexpectedly resulted in a significant visual improvement for
      a 13-year-old boy with orbital hypertelorism who also had bilateral cleft lip and
      palate.

PMID- 22381455
TI  - Can small journals provide leadership?

PMID- 22381456
TI  - Selenium and human health.
AB  - Selenium is incorporated into selenoproteins that have a wide range of
      pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to
      the production of active thyroid hormone. In the past 10 years, the discovery of
      disease-associated polymorphisms in selenoprotein genes has drawn attention to
      the relevance of selenoproteins to health. Low selenium status has been
      associated with increased risk of mortality, poor immune function, and cognitive
      decline. Higher selenium status or selenium supplementation has antiviral
      effects, is essential for successful male and female reproduction, and reduces
      the risk of autoimmune thyroid disease. Prospective studies have generally shown
      some benefit of higher selenium status on the risk of prostate, lung, colorectal,
      and bladder cancers, but findings from trials have been mixed, which probably
      emphasises the fact that supplementation will confer benefit only if intake of a
      nutrient is inadequate. Supplementation of people who already have adequate
      intake with additional selenium might increase their risk of type-2 diabetes. The
      crucial factor that needs to be emphasised with regard to the health effects of
      selenium is the inextricable U-shaped link with status; whereas additional
      selenium intake may benefit people with low status, those with adequate-to-high
      status might be affected adversely and should not take selenium supplements.

PMID- 22381457
TI  - A taxonomic and ecological overview of cheese fungi.
AB  - Cheese is made from milk by a succession of microbes (bacteria, yeasts and fungi)
      that determine the consistency and flavor of the cheese. Apart from the
      emblematic species, Penicillium camemberti and Penicillium roqueforti, cheese
      fungi are not well known. Here we present a taxonomic and phylogenetic overview
      of the most important filamentous cheese Ascomycota based on 133 isolates
      provided by the producers of cheese and cheese starter cultures and 97 isolates
      from culture collections. We checked the congruence of different gene genealogies
      to circumscribe cheese species and our results allow us to propose molecular
      targets for their identification. To study their phylogenetic affiliation, we
      used LSU rDNA and showed that cheese fungi are found in two classes, the
      Eurotiomycetes with Penicillium species (Eurotiales) and Sporendonema
      casei/Sphaerosporium equinum (Onygenales), and the Sordariomycetes with
      Scopulariopsis species (Microascales) and Fusarium domesticum (Hypocreales). Some
      of these fungi, such as, P. camemberti, F. domesticum, Scopulariopsis flava and
      S. casei, are only known from cheeses and are probably adapted to this particular
      habitat, which is extremely rich in protein and fat. Other cheese fungi are
      ubiquitous, such as, P. roqueforti, Scopulariopsis candida and Scopulariopsis
      fusca.

PMID- 22381458
TI  - Interferon gamma and interferon gamma inducible protein-10 in detecting
      tuberculosis infection.
AB  - OBJECTIVE: This study aimed to compare the levels of TB-antigen specific
      Interferon gamma (IFN-gamma) and IFN-gamma inducible protein (IP)-10 in culture
      of whole blood samples from healthy controls (HC) and healthy household contacts
      (HHC). METHODOLOGY: A total of 386 study subjects, which included 186 HC and 200
      HHC, were recruited. QuantiFERON-TB Gold in-tube (QFT-IT) assay was employed to
      measure IFN-gamma levels. IP-10 levels were measured in the supernatants
      collected from QFT-IT tubes. Tuberculin skin test was also performed. RESULTS:
      The levels of TB antigen specific IFN-gamma and IP-10 were significantly higher
      in HHC compared to HC. There was no significant difference observed between
      positivity of QFT-IT and IP-10 in HC and HHC. The positivity of TST was
      significantly lower in subjects <17 year, when compared to IP-10 (p<0.005). The
      reduced cut-off point 0.22IU/ml significantly increased the positivity of QFT-IT
      among children with high risk for latent TB infection (LTBI). CONCLUSIONS:
      Measurement of TB antigen specific IFN-gamma and IP-10 can be potential markers
      for the detection of LTBI.

PMID- 22381459
TI  - Rapid and effective diagnosis of tuberculosis and rifampicin resistance with
      Xpert MTB/RIF assay: a meta-analysis.
AB  - OBJECTIVES: Xpert MTB/RIF (Cepheid) assay has been introduced for the diagnosis
      of tuberculosis (TB) and RIF-resistance. The meta-analysis was used to establish
      the overall accuracy of Xpert MTB/RIF assay for diagnosing TB and RIF-resistance.
      METHODS: Based on comprehensive searches of the Pubmed and Embase, we identified
      outcome data from all articles estimating diagnostic accuracy with Xpert MTB/RIF
      assay. A summary estimation for sensitivity, specificity, diagnostic odds ratios
      (DOR) and the area under the summary ROC curve (AUC) was calculated by using the
      bivariate random-effects approach. RESULTS: The meta-analysis included 18 studies
      (10,224 suspected specimens). The summary estimate was 90.4% (95%CI 89.2%-91.4%)
      for sensitivity, 98.4% (95%CI 98.0%-98.7%) for specificity and 328.3/0.9822 for
      DOR/AUC in pulmonary tuberculosis (PTB). The sensitivity, specificity and DOR/AUC
      of detecting RIF-resistance were 94.1%, 97.0% and 177.8/0.9832, respectively. For
      extrapulmonary tuberculosis, the overall pooled sensitivity was 80.4% and
      specificity was 86.1%. The findings in subgroup analysis were as follows: the
      accuracy of Xpert MTB/RIF assay is higher in smear-positive specimens and the
      sensitivity of diagnosing PTB in adults was higher than that in children (90.8%
      versus 74.3%). CONCLUSIONS: TB and RIF-resistance can be rapidly and effectively
      diagnosed with Xpert MTB/RIF assay.

PMID- 22381461
TI  - A comparative analysis of rapid methods for purification and refolding of
      recombinant bovine prion protein.
AB  - Bacterially-produced recombinant prion protein (rPrP) is a frequently used model
      system for the study of the properties of wild-type and mutant prion proteins by
      biochemical and biophysical approaches. A range of approaches have been developed
      for the purification and refolding of untagged rPrP expressed as inclusion bodies
      in Escherichia coli, including refolding by dialysis and simultaneous on-column
      purification and refolding. In order to perform a higher-throughput analysis of
      different rPrP proteins, an approach that produces highly pure rPrP with a
      minimum of purification steps and a high yield per liter of induced bacterial
      culture is desired. Here, we directly compare purification approaches for
      untagged bovine rPrP as adapted to rapid, small-scale formats useful for higher
      throughput studies. An analysis of protein yield, purity, oxidation, and
      refolding revealed significant differences between preparative methods as adapted
      to the small-scale format, and based on these findings we provide recommendations
      for future purifications. We also describe the utility of a sensitive commercial
      kit for thiol analysis of these preparations, the pH dependence of dimer
      formation during refolding of bovine rPrP, and bovine rPrP binding to cobalt
      affinity resin.

PMID- 22381462
TI  - Antihypertensive activity of recombinant peptide IYPR expressed in Escherichia
      coli as inclusion bodies.
AB  - To produce more angiotensin converting enzyme inhibitory peptides (ACEIP), we
      have established a high-efficiency Escherichia coli expression system. The DNA
      coding sequence for the recombinant protein, which was subcloned into the vector
      pET-30a(+), has been expressed as inclusion bodies in E. coli BL21 (DE3). The
      influences of induction time and concentration of isopropyl-beta-D
      thiogalactopyranoside (IPTG) on the expression of recombinant protein were
      studied. The resulting expression level of the protein accounted for about 31% of
      cellular protein at a temperature of 37 degrees C, IPTG concentration of 0.6mM
      and induction time of 7h. The inclusion bodies were washed, separated from the
      cells, and solubilized with urea. After purification by affinity chromatography,
      the recombinant protein was recovered with a high purity of about 90%. Molecular
      weight of the recombinant protein was measured using Tricine-SDS-PAGE. Peptide
      IYPR was obtained by cleavage of the recombinant protein with trypsin and the
      IC(50) value was 61 mg/L. The antihypertensive activity in spontaneously
      hypertensive rats (SHRs) was also investigated. Single oral administration of
      this peptide in 10-week old SHRs resulted in a significant reduction of systolic
      blood pressure to 50 mm Hg at 4 h. The data obtained provide a good reference for
      further development of peptide Ile-Tyr-Pro-Arg into an effective antihypertensive
      agent for prevention and treatment of hypertension.

PMID- 22381463
TI  - Expression and purification of the active soluble form of Bacillus sphaericus
      binary toxin for structural analysis.
AB  - The binary toxin produced from Bacillus sphaericus is highly toxic against larvae
      of Culex and Anopheles mosquitoes. The two major components of the binary toxin
      are 42-kDa BinA and 51-kDa BinB, which are produced as crystalline inclusions
      during sporulation. Currently, there is no detailed knowledge of the molecular
      mechanism of the binary toxin, mainly due to the lack of structural information.
      Herein, we describe an expression protocol with modified conditions allowing
      production of soluble, biologically active BinA and BinB for further structural
      analysis. The binA and binB genes from B. sphaericus 2297 strain were
      independently cloned and fused with a polyhistidine tag at their N-termini. Both
      (His)(6)-tagged BinA and (His)(6)-tagged BinB were expressed as soluble forms at
      low temperature. Highly pure proteins were obtained after two-step purification
      by Ni-NTA affinity and size exclusion chromatography. In vitro activation by
      trypsin digestion generated a resistant fragment, of 40kDa for BinA, and of 45kDa
      for BinB, and an oligomeric complex of BinA and BinB in solution was observed
      after proteolytic activation. Their functional and structural properties were
      confirmed by a biological assay and far-UV circular dichroism, respectively. The
      mixture of BinA and BinB, either as a protoxin or as a trypsin-activated form,
      exhibited high mosquito-larvicidal activity against Culex quinquefasciatus larvae
      with LC(50) of about 10ng/ml, while no toxicity was observed from the single
      binary toxin component. Results from far-UV circular dichroism of BinA and BinB
      suggest the presence of mainly beta-structure. The expression and purification
      protocols reported here will be useful for the production of the active and
      homogeneous binary toxin to allow further detailed structural investigation.

PMID- 22381464
TI  - Production of human tetraspanin proteins in Escherichia coli.
AB  - Tetraspanins are found in multicellular eukaryotes and are generally thought to
      act as scaffolding proteins, localizing multiple proteins to a specific region of
      the cell membrane. Activities for tetraspanins have been identified in several
      fundamental processes such as motility, cell adhesion, proliferation and viral
      entry. Tetraspanins are also key players in cancer development and progression.
      However, structural and biochemical information on tetraspanins is decidely
      limited, due in no small part to the difficulties associated with expressing
      eukaryotic membrane proteins. In this study, we have used GFP fusions of a
      library of human tetraspanin proteins to identify growth conditions for
      expression in Escherichia coli. Three tetraspanin-GFP proteins could be produced
      at high enough levels to allow subsequent purification, paving the way for future
      structural and biochemical studies.

PMID- 22381465
TI  - Purification, characterization and reconstitution into membranes of the
      oligomeric c-subunit ring of thermophilic F(o)F(1)-ATP synthase expressed in
      Escherichia coli.
AB  - F(o)F(1)-ATP synthase catalyzes ATP synthesis coupled with proton-translocation
      across the membrane. The membrane-embedded F(o) portion is responsible for the
      H(+) translocation coupled with rotation of the oligomeric c-subunit ring, which
      induces rotation of the gamma subunit of F(1). For solid-state NMR measurements,
      F(o)F(1) of thermophilic Bacillus PS3 (TF(o)F(1)) was overexpressed in
      Escherichia coli and the intact c-subunit ring (TF(o)c-ring) was isolated by new
      procedures. One of the key improvement in this purification was the introduction
      of a His residue to each c-subunit that acts as a virtual His(10)-tag of the c
      ring. After solubilization from membranes by sodium deoxycholate, the c-ring was
      purified by Ni-NTA affinity chromatography, followed by anion-exchange
      chromatography. The intactness of the isolated c-ring was confirmed by high
      resolution clear native PAGE, sedimentation analysis, and H(+)-translocation
      activity. The isotope-labeled intact TF(o)c-ring was successfully purified in
      such an amount as enough for solid-state NMR measurements. The isolated TF(o)c
      rings were reconstituted into lipid membranes. A solid-state NMR spectrum at a
      high quality was obtained with this membrane sample, revealing that this
      purification procedure was suitable for the investigation by solid-state NMR. The
      purification method developed here can also be used for other physicochemical
      investigations.

PMID- 22381467
TI  - Synthesis and purification of a toxin-linked conjugate targeting epidermal growth
      factor receptor in Escherichia coli.
AB  - Aberrant epidermal growth factor receptor (EGFR) signaling is a common feature of
      multiple tumor types, including glioblastoma (GBM). As such, EGFR has emerged as
      an attractive target for antitumor therapy. In the present study, we sought to
      develop an immunotoxin capable of specifically targeting EGFR-expressing cells
      and mediating inhibition of cell growth and cell killing. The Luffin P1 (LP1)
      ribosome inactivating protein was chosen to generate a fusion protein,
      antiEGFR/LP1, based upon its potent protein synthesis inhibition and small size
      (5 kDa). LP1 was fused to the C-terminus of an anti-EGFR single-chain antibody
      (scFv). The recombinant antiEGFR/LP1 protein was expressed in Escherichia coli,
      and refolded and purified on an immobilized Ni(2+)-affinity chromatography
      column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western
      blotting analysis revealed that antiEGFR/LP1 was sufficiently expressed. Confocal
      microscopy and flow cytometry demonstrated that antiEGFR/LP1 bound specifically
      to EGFR-positive cells (U251), as almost no binding to EGFR-negative (Jurkat
      cells) was observed under identical time and dosage conditions. Finally, the MTT
      cell viability assay showed that antiEGFR/LP1 elicited obvious cytotoxicity
      toward EGFR-positive tumor cells. Collectively, these results suggest that
      antiEGFR/LP1 is biologically active and specific toward EGFR-positive tumor cells
      and may represent an effective EGFR-targeted cancer therapy.

PMID- 22381466
TI  - Expression and purification of recombinant protein related to DAN and cerberus
      (PRDC).
AB  - Bone morphogenetic proteins (BMPs) are secreted protein ligands that control
      numerous biological processes, such as cell differentiation and cell
      proliferation. Ligands are regulated by a large number of structurally diverse
      extracellular antagonists. PRDC or protein related to DAN and cerberus is a BMP
      antagonist of the DAN family, which is defined by a conserved pattern of cysteine
      residues that form a ring structure. Here we present the expression and
      purification of recombinant mouse PRDC (mPRDC) from bacterial (Escherichia coli)
      inclusion bodies through oxidative refolding. Functional mPRDC was isolated from
      a nonfunctional component through reverse phase chromatography and shown to
      inhibit BMP2 and BMP4 in a cell-based luciferase reporter assay. Recombinant
      mPRDC also bound directly to BMP2, BMP4 and BMP7, but not activin A. Furthermore,
      circular dichroism indicated that mPRDC is folded and contains a higher than
      anticipated helical content for a DAN family member protein.

PMID- 22381468
TI  - Congenital benign mesenchymoma on the palm.

PMID- 22381469
TI  - Effects of interaction of an early experience of reward through maternal contact
      or its denial with social stress during adolescence on the serotonergic system
      and the stress responsiveness of adult female rats.
AB  - Experiences during critical periods, such as the neonatal and adolescence, play a
      critical role in determining adult stress-coping behavior. Based on the
      aforementioned we developed an experimental protocol, which included a neonatal
      experience and a social stress during adolescence. The serotonergic system is
      known as an important modulator of coping ability and, in general, emotional
      balance in both normal and pathological states, such as depression and anxiety,
      for which females are more vulnerable. Thus in the present work we used female
      rats and determined 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and 5
      hydroxytryptamine receptor type 1A (5-HT(1A)) receptor levels in the prefrontal
      cortex (PFC) and the amygdala (AMY). During postnatal days 10-13 (PND 10-13) rat
      pups were exposed to a T-maze, one arm of which lead to the mother. One group of
      animals was allowed contact with the mother (rewarded-receiving expected reward
      (RER)), whereas the other was denied the expected reward (DER). High performance
      liquid chromatography (HPLC) analysis revealed that in both the PFC and in AMY,
      adult RER animals had higher basal 5-HT levels. Furthermore, in the AMY of this
      group of animals, higher levels of 5-HT(1A) receptors were detected by Western
      blot analysis. In adulthood rats were exposed to the Forced Swimming Test/Stress
      (FST/S). RER animals not exposed to the adolescent stress exhibited longer
      immobility time during both the first and second day of FST. Corticosterone
      levels following the FST fell faster in the DER animals. Adolescent stress
      affected the responses to the adult FSS only in the DER animals, which had
      decreased 5-HT in the AMY and increased immobility time on both days of the FST,
      compared with the DER, not stressed in adolescence. The phenotype of the DER
      animals is in line with the "match-mismatch" hypothesis, which states that if two
      events during critical periods of life "match" in being mildly stressful, their
      interaction can be adaptive.

PMID- 22381471
TI  - Detection of Fukushima Daiichi nuclear power plant accident radioactive traces in
      Monaco.
AB  - Daily air monitoring of radionuclides in the Principality of Monaco (43 degrees
      73'N, 7 degrees 43'E) after the Fukushima Daiichi nuclear power plant accident
      showed that only Iodine-131 ((131)I) and Caesium isotopes ((134)Cs and (137)Cs)
      were detected. The peak of (131)I varied and reached its maximum between March
      29th and April 5th, meanwhile both peaks of (134)Cs and (137)Cs arrived later and
      attained a maximum between April 1st and 4th. Their maximum activity
      concentrations in air were 354, 30, and 37 MUBq m(-3) respectively. The (134)Cs
      to (137)Cs activity ratio was close to 1, which is different from that one
      observed after the Chernobyl accident (around 0.54). Up to 95% of caesium
      isotopes were washed out by wet scavenging during 27-28th of March, where the
      maximum deposition rates of (134)Cs and (137)Cs (13.7 and 19.1 mBq m(-2) day(-1),
      respectively) were observed. The significant input of (134)Cs and (137)Cs into
      the Mediterranean seawater column (30 m depth) was detected later, on the 24th of
      May. Radioisotopes of caesium and iodine were found far above the applied
      detection limits, but still with no concern for harmful radiation exposure and
      public health. The contamination gradually decreased in air and activity
      concentrations returned to background values after one or two months.

PMID- 22381470
TI  - Succession of Deferribacteres and Epsilonproteobacteria through a nitrate-treated
      high-temperature oil production facility.
AB  - Members of Epsilonproteobacteria and Deferribacteres have been implied in nitrate
      induced souring control in high-temperature oil production facilities. Here we
      report on their diversity and abundance in the injection and production part of a
      nitrate-treated, off-shore oil facility (Halfdan, Denmark) and aimed to assess
      their potential in souring control. Nitrate addition to deoxygenated seawater
      shifted the low-biomass seawater community dominated by Gammaproteobacteria
      closely affiliated with the genus Colwellia to a high-biomass community with
      significantly higher species richness. Epsilonproteobacteria accounted for less
      than 1% of the total bacterial community in the nitrate-amended injection water
      and were most likely outcompeted by putative nitrate-reducing, methylotrophic
      Gammaproteobacteria of the genus Methylophaga. Reservoir passage and recovery of
      the oil resulted in a significant change in the bacterial community. Members of
      the thermophilic Deferribacteres were the second major fraction of the bacterial
      community in the production water (~30% of the total bacterial community). They
      were not found in the injection water and were therefore assumed to be indigenous
      to the reservoir. Additional diversity analysis and targeted quantification of
      periplasmic nitrate reductase (napA) genes indicated that most resident
      Deferribacteres possessed the functional potential to contribute to nitrate
      reduction in the system. In sum, the dominance of nitrate-reducing
      Deferribacteres and the low relative abundance of Epsilonproteobacteria
      throughout the production facility suggested that the Deferribacteres play a
      major role in nitrate-induced souring control at high temperatures.

PMID- 22381472
TI  - Jejunal intussusception due to malignant phyllodes tumor of the breast.
AB  - Phyllodes tumors are rare fibroepithelial neoplasms of the breast; classified as
      benign, borderline, or malignant based on the mitotic activity, cellular atypia,
      and stromal overgrowth. Wide surgical excision is the treatment of choice. The
      most common locations for metastasis are lung, bone, and liver; small intestinal
      metastasis is extremely rare. Here we present the first patient with jejunal
      metastases and intussusception due to malignant phyllodes tumor of the breast.
      Adjuvant treatment of malignant phyllodes tumor needs to be investigated.

PMID- 22381473
TI  - The role of the lateral dimension of graphene oxide in the regulation of cellular
      responses.
AB  - The nanomaterial graphene oxide (GO) has attracted explosive interests in various
      areas. However, its performance in biological environments is still largely
      unknown, particularly with regard to cellular response to GO. Here we separated
      the GO sheets in different size and systematically investigated size effect of
      the GO in response to different types of cells. In terms of abilities to
      internalize GO, enormous discrepancies were observed in the six cell types, with
      only two phagocytes were found to be capable of internalizing GO. The 2 MUm and
      350 nm GO greatly differed in lateral dimensions, but equally contributed to the
      uptake amount in macrophages. Similar amounts of antibody opsonization and active
      Fcgamma receptor-mediated phagocytosis were demonstrated the cause of this
      behavior. In comparison with the nanosized GO, the GO in micro-size showed
      divergent intracellular locations and induced much stronger inflammation
      responses. Present study provided insight into selective internalization, size
      independent uptake, and several other biological behaviors undergone by GO. These
      findings might help build necessary knowledge for potential incorporation of the
      unique two-dimensional nanomaterial as a biomedical tool, and for avoiding
      potential hazards.

PMID- 22381474
TI  - Ectopic bone formation by 3D porous calcium phosphate-Ti6Al4V hybrids produced by
      perfusion electrodeposition.
AB  - Successful clinical repair of non-healing skeletal defects requires the use of
      bone substitutes with robust bone inductivity and excellent biomechanical
      stability. Thus, three-dimensionally functionalised porous calcium phosphate
      Ti6Al4V (CaP-Ti) hybrids were produced by perfusion electrodeposition, and the in
      vitro and in vivo biological performances were evaluated using human periosteum
      derived cells (hPDCs). By applying various current densities at the optimised
      deposition conditions, CaP coatings with sub-micrometer to nano-scale porous
      crystalline structures and different ion dissolution kinetics were deposited on
      the porous Ti6Al4V scaffolds. These distinctive physicochemical properties caused
      a significant impact on in vitro proliferation, osteogenic differentiation, and
      matrix mineralisation of hPDCs. This includes a potential role of hPDCs in
      mediating osteoclastogenesis for the resorption of CaP coatings, as indicated by
      a significant down-regulation of osteoprotegerin (OPG) gene expression and by the
      histological observation of abundant multi-nucleated giant cells near to the
      coatings. By subcutaneous implantation, the produced hybrids induced ectopic bone
      formation, which was highly dependent on the physicochemical properties of the
      CaP coating (including the Ca(2+) dissolution kinetics and coating surface
      topography), in a cell density-dependent manner. This study provided further
      insight on stem cell-CaP biomaterial interactions, and the feasibility to
      produced bone reparative units that are predictively osteoinductive in vivo by
      perfusion electrodeposition technology.

PMID- 22381475
TI  - The cytotoxic and immunogenic hurdles associated with non-viral mRNA-mediated
      reprogramming of human fibroblasts.
AB  - Delivery of reprogramming factor-encoding mRNAs by means of lipofection in
      somatic cells is a desirable method for deriving integration-free iPSCs. However,
      the lack of reproducibility implies there are major hurdles to overcome before
      this protocol becomes universally accepted. This study demonstrates the
      functionality of our in-house synthesized mRNAs expressing the reprogramming
      factors (OCT4, SOX2, KLF4, c-MYC) within the nucleus of human fibroblasts.
      However, upon repeated transfections, the mRNAs induced severe loss of cell
      viability as demonstrated by MTT cytotoxicity assays. Microarray-derived
      transcriptome data revealed that the poor cell survival was mainly due to the
      innate immune response triggered by the exogenous mRNAs. We validated the
      influence of mRNA transfection on key immune response-associated transcript
      levels, including IFNB1, RIG-I, PKR, IL12A, IRF7 and CCL5, by quantitative real
      time PCR and directly compared these with the levels induced by other methods
      previously published to mediate reprogramming in somatic cells. Finally, we
      evaluated chemical compounds (B18R, chloroquine, TSA, Pepinh-TRIF, Pepinh-MYD),
      known for their ability to suppress cellular innate immune responses. However,
      none of these had the desired effect. The data presented here should provide the
      basis for further investigations into other immunosuppressing strategies that
      might facilitate efficient mRNA-mediated cellular reprogramming in human cells.

PMID- 22381476
TI  - Recovery of Fascioloides magna (Digenea) population in spite of treatment
      programme? Screening of Galba truncatula (Gastropoda, Lymnaeidae) from Lower
      Austria.
AB  - During the past decade, Fascioloides magna, the large American liver fluke, has
      spread within free-living deer in wetlands of the Danube in Lower Austria. The
      aim of this study was to determine the current infection rates with F. magna and
      other digenean parasites in the intermediate host snail Galba truncatula from
      risk areas in Lower Austria. A total of 3444 G. truncatula were collected and
      examined microscopically for the presence of digenean trematodes. A set of
      randomly selected snails and isolated trematode stages were also investigated
      molecular biologically by PCR and sequencing. Digenean parasites were detected
      with a prevalence of 2.41% (1.83% Paramphistomoidea; 0.46% Echinostomatoidea;
      0.09% Strigeida; 0.06% Plagiorchiida). F. magna was found with an overall
      prevalence of 0.23%, which may indicate a recovery of the parasite population in
      spite of an ongoing triclabendazole treatment programme. Moreover, high risk
      areas and a seasonality of infections were observed.

PMID- 22381477
TI  - Spatial dependency of shoulder muscle demands in horizontal pushing and pulling.
AB  - Pushing and pulling account for nearly half of all manual material handling
      tasks. The purpose of this investigation was to develop a 3-D spatial muscle
      activity map for the right upper extremity during pushing and pulling tasks.
      Nineteen males performed 140 ramped directional hand exertions (70 push; 70 pull)
      at locations along three axes aligned with the anatomical planes.
      Electromyography (EMG) of 14 sites on the right upper extremity was recorded. Two
      directional 3-way repeated measures ANOVAs assessed the influence of hand
      position on EMG. Hand position and exertion direction influenced total and
      individual muscle demand. During pulling exertions, all three hand location
      parameters influenced total muscle activity (p < 0.001) and similarly in pushing
      exertions (p < 0.002), though less pronounced than in pulling. Data were used to
      create equations to predict the muscle activity of untested hand locations for
      novel work design scenarios.

PMID- 22381478
TI  - American Foulbrood in Uruguay: twelve years from its first report.
AB  - Paenibacillus larvae is the causative agent of American Foulbrood (AFB), a
      deleterious disease that affects honeybees. In Uruguay it was first reported in
      1999. In 2001 the bacterium was spread all over the country, and its prevalence
      in honey was estimated in 51%. Two P. larvae genotypes were found; ERIC I - BOX
      A, worldwide distributed and ERIC I - BOX C, exclusively detected in Argentina
      until then. In the present manuscript we analyzed the evolution of AFB outbreaks
      from 1999 to 2009, presented a new nation-wide survey carried out during 2011
      when a prevalence of 2% was found and discuss national strategies for prevention
      of the disease. Since Uruguay is a small country where almost all beekeepers are
      registered, Uruguayan experience can be useful to be applied in other countries.

PMID- 22381479
TI  - If it looks too good to be true...

PMID- 22381480
TI  - Ethics: Put education ahead of new limitations.

PMID- 22381481
TI  - Ethics: Publish or perish.

PMID- 22381482
TI  - Ethics: Schools should prepare residents for real-world experience.

PMID- 22381483
TI  - Editorial: Other specialists can provide valuable insight.

PMID- 22381484
TI  - Discretion in advertising: it's up to you.

PMID- 22381486
TI  - Comparison of the orthodontic load systems created with elastomeric power chain
      to close extraction spaces on different rectangular archwires.
AB  - INTRODUCTION: The 3-dimensional load system (forces and moments) was quantified
      at the canine bracket during space closure with sliding mechanics with
      elastomeric chain on dry and wet stainless steel and beta-titanium 0.019 * 0.025
      in archwires. METHODS: A custom-made maxillary dentoform simulating first
      premolar extractions was attached to an orthodontic force tester. The canine was
      attached to a load cell through an adaptor with silicone simulating the
      periodontal ligament. The orthodontic force tester simultaneously measured the
      entire load system produced at the canine bracket by an elastomeric chain. The
      effects of archwire material, time (activation and 1 hour), and lubrication were
      analyzed by using 3-way repeated measures analysis of variance (ANOVA, alpha =
      0.05). RESULTS: Stainless steel provided a greater (P = 0.001) load system than
      did beta-titanium. The force was greatest on the canine in the lingual axis. The
      greatest moment was about the y-axis. The moment-to-force ratio, the most
      critical ratio, was greater for beta-titanium than stainless steel; however, both
      were close to the ideal 10:1. CONCLUSIONS: With a stainless steel archwire for
      retraction sliding mechanics, a canine will experience a greater load system in
      all 3 dimensions than with a beta-titanium wire. Both archwires produced a moment
      to-force ratio adequate for translation.

PMID- 22381487
TI  - Improvement of nasal airway ventilation after rapid maxillary expansion evaluated
      with computational fluid dynamics.
AB  - INTRODUCTION: Rapid maxillary expansion is known to improve nasal airway
      ventilation. However, it is difficult to precisely evaluate this improvement with
      conventional methods. The purpose of this longitudinal study was to use
      computational fluid dynamics to estimate the effect of rapid maxillary expansion.
      METHODS: Twenty-three subjects (9 boys, 14 girls; mean ages, 9.74 +/- 1.29 years
      before rapid maxillary expansion and 10.87 +/- 1.18 years after rapid maxillary
      expansion) who required rapid maxillary expansion as part of their orthodontic
      treatment had cone-beam computed tomography images taken before and after rapid
      maxillary expansion. The computed tomography data were used to reconstruct the 3
      dimensional shape of the nasal cavity. Two measures of nasal airflow function
      (pressure and velocity) were simulated by using computational fluid dynamics.
      RESULTS: The pressure after rapid maxillary expansion (80.55 Pa) was
      significantly lower than before rapid maxillary expansion (147.70 Pa), and the
      velocity after rapid maxillary expansion (9.63 m/sec) was slower than before
      rapid maxillary expansion (13.46 m/sec). CONCLUSIONS: Improvement of nasal airway
      ventilation by rapid maxillary expansion was detected by computational fluid
      dynamics.

PMID- 22381488
TI  - Effects of thread depth, taper shape, and taper length on the mechanical
      properties of mini-implants.
AB  - INTRODUCTION: The primary stability of a mini-implant is critical, since most
      orthodontic mini-implant failures occur at an early stage. As orthodontic mini
      implants have restrictions in diameter and length, an optimal design of the shape
      is important for sufficient primary stability. The purpose of this study was to
      investigate the influence of various mini-implants design factors, including
      thread depth, degree of taper, and taper length on insertion torque, pullout
      strength, stiffness, and screw displacement before failure. METHODS: Finite
      element analyses were conducted first for identification of optimal design
      parameters. Four types of mini-implants with different design parameters were
      then custom manufactured and tested mechanically. All mechanical tests were
      performed in artificial bone with homogenous density to remove the variability
      associated with bone. RESULTS: Finite element results showed that, for mini
      implants with a fixed external diameter of 2 mm, a thread length of 9.82 mm, and
      a pitch of 0.75 mm, those with greater thread depths, smaller taper degrees, and
      shorter taper lengths generated higher maximum stresses on the bone and thread
      elements. These mini-implants also had larger relative displacements. Maximum
      pullout resistance was attained with a core/external diameter ratio of 0.68. All
      mechanical results were compatible with the findings in the finite element
      analyses. CONCLUSIONS: Modification of the mini-implant design can substantially
      affect the mechanical properties. The finite element method is an effective tool
      to identify optimal design parameters and allow for improved mini-implant
      designs.

PMID- 22381489
TI  - Efficacy of low-intensity laser therapy in reducing treatment time and
      orthodontic pain: a clinical investigation.
AB  - INTRODUCTION: The long duration of orthodontic treatment is a major concern for
      patients. A noninvasive method of accelerating tooth movement in a physiologic
      manner is needed. The aim of this study was to evaluate of the efficacy of low
      intensity laser therapy in reducing orthodontic treatment duration and pain.
      METHODS: Twenty patients requiring extraction of first premolars were selected
      for this study. We used a randomly assigned incomplete block split-mouth design.
      Individual canine retraction by a nickel-titanium closed-coil spring was studied.
      The experimental side received infrared radiation from a semiconductor (aluminium
      gallium arsenide) diode laser with a wavelength of 810 nm. The laser regimen was
      applied on days 0, 3, 7, and 14 in the first month, and thereafter on every 15th
      day until complete canine retraction was achieved on the experimental side. Tooth
      movement was measured on progress models. Each patient's pain response was ranked
      according to a visual analog scale. RESULTS: An average increase of 30% in the
      rate of tooth movement was observed with the low-intensity laser therapy. Pain
      scores on the experimental sides were significantly lower compared with the
      control sides. CONCLUSIONS: Low-intensity laser therapy is a good option to
      reduce treatment duration and pain.

PMID- 22381490
TI  - Perceived vs measured forces of interarch elastics.
AB  - INTRODUCTION: Orthodontists depend on perceptions derived from education and
      clinical experience to judge the optimal forces in patient treatment. The purpose
      of this study was to survey practicing orthodontists to determine the interarch
      latex elastic forces they prescribe in different malocclusion scenarios. METHODS:
      Thirty orthodontists were presented with 4 clinical scenarios on study models,
      including Class II and Class III malocclusions in edgewise and light wires. These
      orthodontists described the size and location of the elastics they would use. The
      forces produced by the prescribed elastics were measured and compared with actual
      dry forces measured on a testing machine. RESULTS: The orthodontists' force
      recommendations were a mean of 277 +/- 89 g and a median of 256 g (range, 132-464
      g) for a Class II malocclusion with edgewise wires; a mean of 183 +/- 59 g and a
      median of 177 g (range, 59-284 g) for a Class II malocclusion with light wires; a
      mean of 290 +/- 83 g and a median of 305 g (range, 151-562 g) for a Class III
      malocclusion with edgewise wires; and a mean of 216 +/- 66 g and a median of 209
      g (range, 119-344 g) for a Class III malocclusion with light wires. The force
      levels for light wires were statistically significantly lower than for edgewise
      wires. CONCLUSIONS: There were considerable variations in the forces selected for
      all cases. "Expert" recommendations fell within 1 SD of the mean of the
      orthodontists' recommendations except for the light-wire Class III scenario.
      Since latex elastic force decays significantly during a patient's use, elastics
      should be selected with initially higher forces than desired.

PMID- 22381491
TI  - Radiographic study of delayed tooth development in patients with dental agenesis.
AB  - INTRODUCTION: The aims of this study were to compare the radiographic development
      of permanent teeth in a group of children affected by dental agenesis with an
      unaffected control group and to determine the effects of confounding factors
      including the severity of the dental agenesis, age, sex, ethnicity, and the
      number of stages used to estimate dental age. METHODS: A single-center
      retrospective cross-sectional study of dental panoramic tomographs was undertaken
      between July 2007 and April 2008 in a postgraduate teaching school. A total of
      139 patients (aged 9-18 years) were recruited from the orthodontic clinic on the
      basis of predetermined inclusion and exclusion criteria to either a dental
      agenesis group or a control group. Dental panoramic tomograms were assessed, and
      the stages of development of the permanent teeth in the left maxillary and left
      mandibular regions were scored by using the 12 stages of Haavikko and the 8
      stages of Demirjian and Goldstein. For each tooth scored, the mean dental age and
      standard error were determined by using the dental age assessment method, and an
      estimated dental age for each subject was derived by using the weighted average
      method. RESULTS: A statistically significant delay in dental age was found in the
      patients with dental agenesis compared with the control group. The dental age
      assessment method of Haavikko showed a delay of 1.20 years (SD, 1.74), and the
      method of Demirjian and Goldstein showed a delay of 1.64 years (SD, 1.75). It was
      also observed that older patients with dental agenesis had greater delays in
      tooth formation (P <0.001). With the Haavikko method, for every year of
      chronologic age, the delay in dental age increased by 0.53 year; with the
      Demirjian and Goldstein method, the delay increased by 0.48 year. A significant
      association was seen between the severity of dental agenesis and the delay in
      dental age (P <0.01). With both methods, for each additional developmentally
      absent tooth, the dental age was delayed by 0.13 year (lower confidence interval,
      -0.22; upper confidence interval, 0.35). There was no evidence that sex or
      ethnicity has an effect on the delay in dental age in patients with dental
      agenesis. CONCLUSIONS: The development of permanent teeth in children with dental
      agenesis is delayed when compared with a matched control group. The severity of
      dental agenesis affected the magnitude of the delay (P <0.01). This delay has
      implications in orthodontic treatment planning and in the estimation of age for
      legal, immigration, archaeological, and forensic purposes.

PMID- 22381492
TI  - Viscoelastic properties of elastomeric chains: an investigation of pigment and
      manufacturing effects.
AB  - INTRODUCTION: Orthodontic elastomeric chains are commercially available in
      various colors from many manufacturers. In this study, we investigated the
      viscoelastic properties of elastomeric chains using dynamic mechanical analysis
      to perform color and brand comparisons. METHODS: Ten colors of Sunburst chains
      (GAC International, Bohemia, NY) were selected for the color study. Three colors
      of Sunburst, Bobbin Alastik (3M Unitek, Monrovia, Calif), and Energy (Rocky
      Mountain Orthodontics, Denver, Colo) chains were selected for the brand study.
      Nine specimens of each type were measured and tested. Dynamic mechanical analysis
      was performed at room temperature at 8 frequencies ranging from 0.125 to 16.0 Hz.
      Three variables (storage stiffness, loss stiffness, and tan delta) were analyzed
      by using repeated-measures analysis of variance (ANOVA) and pairwise t tests,
      comparing all frequencies for each specimen type and all specimen types for each
      frequency (with Bonferroni corrections). Significance was set at alpha = 0.05.
      RESULTS: Significant differences were found among all specimen dimensions, all
      frequencies, and all 3 dynamic mechanical analysis variables in both the color
      and brand studies. Comparisons focused on tan delta, which does not depend on
      specimen dimensions as do storage stiffness and loss stiffness. CONCLUSIONS:
      Statistically significant differences in tan delta values among colors were
      relatively small, so the clinical significance is questionable and requires
      further investigation. Differences in tan delta values among brands were greater
      and more likely to be clinically significant. Further studies are needed to
      relate viscoelastic properties to force decay.

PMID- 22381493
TI  - Three-dimensional finite element analysis of strength, stability, and stress
      distribution in orthodontic anchorage: a conical, self-drilling miniscrew implant
      system.
AB  - INTRODUCTION: The aims of this study were to analyze the stress distribution and
      displacement patterns that develop in an orthodontic miniscrew implant and its
      surrounding osseous structures for 2 implant materials under horizontal and
      torsional loading, with no ossseointegration. METHODS: A numeric approach was
      adopted. The finite element method was used to determine the stress and
      displacement of the various components at a given time after miniscrew implant
      application, when, due to viscoelastic relaxation effects, the only remaining
      stress field was from the application of the orthodontic load. RESULTS: Stress
      distribution was not significantly different between the 2 types of implant
      material. Increased stress values were located at the necks of the implants and
      the surrounding cortical bone. Bending of the titanium miniscrew was observed in
      the neck region under horizontal traction. CONCLUSIONS: The differences between
      the values of stress and displacement we obtained for the 2 types of miniscrew
      were too small to be clinically significant. Optimization of the miniscrew
      implant composed of the titanium alloy might be achieved by increasing the bulk
      (quantity) of the material in the neck region. The miniscrew implant can be
      immediately loaded and used for group movement of teeth.

PMID- 22381494
TI  - Development of white spot lesions during orthodontic treatment: perceptions of
      patients, parents, orthodontists, and general dentists.
AB  - INTRODUCTION: Despite the many advances to improve the practice of orthodontics,
      white spot lesions, or decalcifications, remain a common complication in patients
      with poor oral hygiene. The purpose of this study was to assess the perceptions
      and level of awareness of patients, parents, orthodontists, and general dentists
      toward the development of white spot lesions during orthodontic treatment.
      METHODS: This was a prospective epidemiologic survey of the perceptions of
      orthodontic patients (n = 315), parents (n = 279), orthodontists (n = 305), and
      general dentists (n = 191) regarding the significance, prevention, and treatment
      of white spot lesions. RESULTS: All surveyed groups indicated that white spot
      lesions detracted from the overall appearance of straight teeth, attributed
      primary responsibility for the prevention of white spot lesions to the patients
      themselves, and thought that the general dentist should be responsible for
      treating white spot lesions. Patients regarded themselves as ultimately
      responsible for the prevention of white spot lesions (P <0.05). CONCLUSIONS: The
      patients, parents, orthodontists, and general dentists had similar perceptions
      regarding the significance, prevention, and treatment of white spot lesions. All
      groups indicated that patients were the most responsible for the prevention of
      white spot lesions. Communication among patients, parents, orthodontists, and
      general dentists needs to improve to decrease the incidence of white spot lesions
      in the orthodontic population.

PMID- 22381495
TI  - Stress and displacement between maxillary protraction with miniplates placed at
      the infrazygomatic crest and the lateral nasal wall: a 3-dimensional finite
      element analysis.
AB  - INTRODUCTION: The purpose of this study was to compare the pattern and amount of
      stress and displacement between maxillary protraction with miniplates placed at
      the infrazygomatic crest and the lateral nasal wall. METHODS: Three-dimensional
      finite element models for the skull and the curvilinear type of miniplate were
      constructed. After a protraction force (500 g/side) was applied to the distal end
      of the miniplate with a forward and 30 degrees  downward vector to the maxillary
      occlusal plane, stress distributions in the circummaxillary sutures and
      displacements of the surface landmarks were analyzed. RESULTS: There was a
      difference in the maximum stress distribution area according to the site of the
      miniplate: infrazygomatic crest and middle part of the maxilla in the
      infrazygomatic crest and paranasal area adjacent to the pyriform aperture in the
      lateral nasal wall. Stress values of the frontonasal, frontomaxillary,
      zygomaticomaxillary, and pterygomaxillary sutures were greater in the
      infrazygomatic crest than in the lateral nasal wall. The site of the miniplate
      produced differences in the major displacement areas: infrazygomatic crest,
      maxillary dentition, anterior maxilla, and upper part of the maxillary tuberosity
      in the infrazygomatic crest and the lateral nasal wall, maxillary dentition,
      anterior maxilla, and lower part of the maxillary tuberosity in the lateral nasal
      wall. The lateral nasal wall exhibited forward, downward, and outward
      displacements of ANS, Point A, and prosthion. However, the infrazygomatic crest
      showed forward and upward displacements of ANS, Point A, and prosthion, and
      outward displacement of the zygomatic process of the maxilla and the maxillary
      process of the zygomatic bone. CONCLUSIONS: The site of miniplate placement
      should be considered to obtain proper stress and displacement values in different
      areas with maxillary hypoplasia.

PMID- 22381496
TI  - Long-term stability of conservative orthodontic treatment in a patient with
      rheumatoid arthritis and severe condylar resorption.
AB  - Rheumatoid arthritis is a chronic inflammatory condition that can result in
      progressive destruction of the articular surfaces of the joints, including the
      temporomandibular joint. The purpose of this article is to report the
      conservative correction of a Class II malocclusion in a woman with rheumatoid
      arthritis. The patient was 32 years 6 months old at the start of treatment. She
      had a convex profile and a skeletal Class II jaw-base relationship caused by
      severe condylar resorption. An anterior open bite of -2.0 mm and an excessive
      overjet of 10.0 mm were observed. Severe crowding was shown in the mandibular
      incisors. After 8 months of splint therapy, all first premolars were extracted,
      and 0.018-in preadjusted edgewise appliances were placed in both arches. Class II
      elastics were used during space closure. After 41 months of active orthodontic
      treatment, an acceptable occlusion was achieved, and the facial profile was
      considerably improved. From the cephalometric evaluations, the mandible was
      rotated counterclockwise, and the mandibular plane angle was significantly
      decreased. However, the anteroposterior position of the chin was not changed. The
      condylar resorption was not changed during and after orthodontic treatment.
      Conclusively, the proper facial profile was maintained, and the occlusion was
      stable after a 5-year retention period. Our results suggest the possibility of
      compromised treatment in a Class II malocclusion with an anterior open bite
      because of rheumatoid arthritis.

PMID- 22381497
TI  - Orthodontic treatment for a patient with a unilateral cleft lip and palate and
      congenitally missing maxillary lateral incisors and left second premolar.
AB  - Treatment of a patient with a cleft lip and palate can be challenging. A woman,
      aged 26 years 8 months, was referred for orthodontic evaluation of her anterior
      crossbite. She was unhappy with the unesthetic appearance of her maxillary
      anterior teeth, which were behind her mandibular anterior teeth. She had a
      unilateral cleft lip and palate and had received primary lip repair and
      palatoplasty when she was younger, as well as rhinoplasty and a secondary lip
      repair when she was 15. At the pretreatement evaluation, she had a concave
      profile with an overjet of -9 mm, a Wits appraisal of -3.8 mm, and a transposed
      ectopic maxillary right canine. She was treated with orthodontic treatment alone,
      without orthognathic surgery. The posttreatment records 9 years later showed
      excellent results with good occlusion, facial balance and harmony, and long-term
      stability.

PMID- 22381498
TI  - A practical and effective method to increase the capacity of screws used for
      palatal disjunction.
AB  - In clinical situations involving accentuated atresia in the maxillary arch,
      palatal disjunction is called for. This treatment often requires an appliance
      change to achieve the desired movement. The aim of this article was to
      demonstrate a simple and effective method to increase the capacity of the
      expander screw and thus avoid the need to remove and replace it.

PMID- 22381499
TI  - Interactive distance learning for orthodontic residents: utilization and
      acceptability.
AB  - INTRODUCTION: Sharing resources through distance education has been proposed as 1
      way to deal with a lack of full-time faculty in orthodontic residency programs.
      To keep distance education for orthodontic residents as cost-effective as
      possible while retaining interaction, we developed a "blended" interactive
      distance learning approach that combines observation of Web-based seminars with
      live postseminar discussions. For the 2009-2010 academic year, a grant from the
      American Association of Orthodontists opened access to the blended learning
      experience to all orthodontic programs in the United States and Canada. The
      specific aims of this project were to (1) measure programmatic interest in using
      blended distance learning, (2) determine resident and faculty interest, (3)
      determine the seminars' perceived usefulness, and (4) elicit feedback regarding
      future use. METHODS: Participants in this project were expected to (1) read all
      assigned articles before viewing a recorded seminar, (2) watch a 1 to 1.5 hour
      recording of an actual interactive seminar on a Web site, and (3) participate in
      a 30-minute follow-up discussion immediately after watching the recorded seminar
      either with a faculty member at the participating institution or via a
      videoconference with the leader of the Web-based seminar. The residents and
      faculty then completed surveys about the experience. RESULTS: Half (52%) of the
      63 orthodontic programs in the United States fully participated in this project.
      The blended approach to distance learning was judged to be effective and
      enjoyable; faculty members were somewhat more enthusiastic about the experience
      than were residents. Most residents were not adequately prepared for the seminars
      (only 14% read all preparatory articles in depth); this impacted their perception
      of the effectiveness and enjoyability of the experience (P = 0.0016). Prepared
      residents reported a greater ability to learn from the seminars (P = 0.0035) than
      those who did not read, and also indicated that they were more likely to use the
      seminars again (P = 0.0018). Despite feedback regarding the need for technologic
      improvements of the recorded seminars, such as better editing, more frequent
      slides, quicker pace, and improved sound quality, most residents and faculty
      agreed that they would like to use this approach to distance learning again.
      CONCLUSIONS: Blended distance learning is an acceptable method of instruction
      that allows residents to access various experts, supplement traditional
      instructor-led training, and ease the strain of current faculty shortages. The
      content of the recorded seminars needs to remain evidence-based, and some
      technologic aspects of the recordings should be improved.

PMID- 22381500
TI  - Litigation and legislation. What to say given what was said.

PMID- 22381501
TI  - Blinding or masking.

PMID- 22381502
TI  - Correction of collapsed occlusion with degenerative joint disease focused on the
      mandibular arch and timely relocation of a miniplate.
AB  - This report describes a novel concept of 3-dimensional tooth movement by using
      biocreative therapy to provide unrestricted distal movement of the full
      mandibular dentition. The patient was a 26-year-old Korean woman with multiple
      problems, including a collapsed occlusion, a full-step Class III relationship
      with posterior open bite, a crossbite, temporomandibular joint pain, and a
      tendency for root resorption. Two orthodontic miniplates with tubes were
      initially placed on both retromolar pads for distalization; 1 miniplate was
      relocated to the anterior region for angulation and vertical control of the
      anterior teeth. The total treatment period was 13 months. The occlusion was
      finished in Class I molar and canine relationships with optimal overjet and
      overbite. Posttreatment records 2.5 years later showed a stable treatment
      outcome. The results suggest that an orthodontic miniplate is an efficient tool
      for the treatment of a collapsed occlusion by changing the affected arch only.

PMID- 22381503
TI  - Editorial: combat orthopaedics for the civilian provider, with special emphasis
      on the dismounted complex blast injury.

PMID- 22381504
TI  - Dismounted Complex Blast Injury.
AB  - The severe Dismounted Complex Blast Injury (DCBI) is characterized by high-energy
      injuries to the bilateral lower extremities (usually proximal transfemoral
      amputations) and/or upper extremity (usually involving the non-dominant side), in
      addition to open pelvic injuries, genitourinary, and abdominal trauma. Initial
      resuscitation and multidisciplinary surgical management appear to be the keys to
      survival. Definitive treatment follows general principals of open wound
      management and includes decontamination through aggressive and frequent
      debridement, hemorrhage control, viable tissue preservation, and appropriate
      timing of wound closure. These devastating injuries are associated with
      paradoxically favorable survival rates, but associated injuries and higher
      amputation levels lead to more difficult reconstructive challenges.

PMID- 22381505
TI  - Complex dismounted IED blast injuries: the initial management of bilateral lower
      extremity amputations with and without pelvic and perineal involvement.
AB  - The magnitude of recent combat blast injuries sustained by forces fighting in
      Afghanistan has escalated to new levels with more troops surviving higher-energy
      trauma. The most complex and challenging injury pattern is the emerging frequency
      of high-energy IED casualties presenting in extremis with traumatic bilateral
      lower extremity amputations with and without pelvic and perineal blast
      involvement. These patients require a coordinated effort of advanced trauma and
      surgical care from the point of injury through definitive management. Early
      survival is predicated upon a balance of life-saving damage control surgery and
      haemostatic resuscitation. Emergent operative intervention is critical with
      timely surgical hemostasis, adequate wound decontamination, revision amputations,
      and pelvic fracture stabilization. Efficient index surgical management is
      paramount to prevent further physiologic insult, and a team of orthopaedic and
      general surgeons operating concurrently may effectively achieve this. Despite the
      extent and complexity, these are survivable injuries but long-term followup is
      necessary.

PMID- 22381506
TI  - Resuscitation and blood utilization guidelines for the multiply injured, multiple
      amputee.
AB  - Given the current tempo of overseas contingency operations, military orthopaedic
      surgeons are increasingly performing their duties in an austere environment. At
      Level 1 trauma centers and combat support hospitals, resources tend to be more
      abundant than in less "metropolitan'' locations. Combat casualty care has
      reinforced the idea of a multidisciplinary team approach to severely injured
      trauma patients. During mass casualty situations, as seen recently in Haiti and
      in the wake of Hurricane Katrina, all members of the trauma team may need to
      perform duties on the periphery of their comfort zone. Early involvement of
      orthopaedic surgeons in damage control surgery, as well as resuscitation, are
      critical to the survival of patients with high amputations, multiple amputations,
      open pelvic injuries, and mangled extremities common in high-energy penetrating
      and blast-induced trauma. This article introduces the concept of Damage Control
      Resuscitation to the orthopaedic surgeon, and also presents a treatment guideline
      for use as appropriate.

PMID- 22381507
TI  - Damage control and austere environment external fixation: techniques for the
      civilian provider.
AB  - Extremity injuries associated with natural disasters and combat are typically
      high-energy, often open injuries, and routinely represent only part of the scope
      of injury to a poly-traumatized patient. The early management of these injuries
      is normally performed in austere environments, and relies heavily on the
      principles of damage control orthopaedics, with external fixation of associated
      long bone and peri-articular fractures. While the general principles of ATLS,
      wound management, and external fixation do not differ from that performed in the
      setting of civilian trauma, there are special considerations and alterations in
      standard practice that become necessary when providing this care in an austere
      environment. The purpose of this article is to review the principles and
      techniques of damage control orthopaedics and external fixation in the management
      of extremity trauma in the setting of combat- and natural disaster-related
      injuries.

PMID- 22381508
TI  - Dismounted complex blast injuries: patterns of injuries and resource utilization
      associated with the multiple extremity amputee.
AB  - The objective of this report is to analyze the resource utilization and injury
      patterns of complex dismounted blast injuries. A retrospective review of U.S.
      service members injured in combat between 2007 and 2010 was conducted. Data
      analyzed included age, injury mechanism, amputated limbs, number and type of
      associated injuries, blood products utilized, intensive care unit length of stay
      (ILOS), hospital length of stay (HLOS) and the Injury Severity Score (ISS).
      Patients were stratified based on the number of amputations. Sixty-three patients
      comprised the multiple extremity amputation (MEA) group. Ninety-eight percent
      sustained injuries from an improvised explosive device (IED) and 96% were
      dismounted. The ISS, number of surgical encounters, blood products utilized and
      ILOS were all clinically significantly different than controls. Care of multiple
      extremity amputees involves the utilization of significant resources. This
      knowledge may better help surgeons and administrators allocate assets at
      hospitals, both military and civilian, who care for this complex and challenging
      patient population.

PMID- 22381509
TI  - Combat-related hemipelvectomy.
AB  - Traumatic and trauma-related hemipelvectomies are rare and severe life
      threatening injuries. Rapid hemostasis, early aggressive resuscitation,
      amputation completion, and wound debridement are the mainstays of initial
      treatment. Second-look debridements and delayed wound closure are mandatory. A
      multidisciplinary team is necessary in order to treat associated injuries as well
      assist with eventual rehabilitation. Adherence to specific treatment tenants
      outlined herein may minimize mortality and secondary morbidity, improving patient
      outcomes following these devastating injuries.

PMID- 22381510
TI  - Ligamentous knee injuries in amputees.
AB  - Combat-related musculoskeletal injuries occur commonly during military conflicts,
      as in Iraq and Afghanistan, and are caused by high-energy blasts. Ligamentous
      knee injuries resulting from these blasts are often associated with lower
      extremity fractures or traumatic, transtibial amputations. Ligamentous knee
      injuries in amputees are often difficult to diagnose for a variety of reasons,
      including massive soft tissue trauma and delayed ambulation. While the algorithm
      for treatment is similar in non-combat, multi-ligamentous knee injuries, the
      timing of surgical intervention, graft choices, and methods of fixation are more
      limited. Additionally, the presence of traumatic brain injury and associated
      extremity trauma make rehabilitation of these injuries much more complicated.
      Despite these challenges, the recognition and treatment of ligamentous knee
      injuries in amputees is critical to returning these patients to an active
      lifestyle.

PMID- 22381511
TI  - Advanced rehabilitation techniques for the multi-limb amputee.
AB  - Advances in combat casualty care have contributed to unprecedented survival rates
      of battlefield injuries, challenging the field of rehabilitation to help injured
      service members achieve maximal functional recovery and independence. Nowhere is
      this better illustrated than in the care of the multiple-limb amputee.
      Specialized medical, surgical, and rehabilitative interventions are needed to
      optimize the care of this unique patient population. This article describes
      lessons learned at Walter Reed National Military Medical Center Bethesda in
      providing advanced therapy and prosthetics for combat casualties, but provides
      guidelines for all providers involved in the care of individuals with amputation.

PMID- 22381512
TI  - Prosthetic advances.
AB  - Much of the current prosthetic technology is based on developments that have
      taken place during or directly following times of war. These developments have
      evolved and improved over the years, and now there are many more available
      options to provide a comfortable, cosmetic, and highly functional prosthesis.
      Even so, problems with fit and function persist. Recent developments have
      addressed some of the limitations faced by some military amputees. On-board
      microprocessor-controlled joints are making prosthetic arms and legs more
      responsive to environmental barriers and easier to control by the user. Advances
      in surgical techniques will allow more intuitive control and secure attachment to
      the prosthesis. As surgical techniques progress and permeate into standard
      practice, more sophisticated powered prosthetic devices will become commonplace,
      helping to restore neuromuscular loss of function. Prognoses following amputation
      will certainly rise, factoring into the surgeon's decision to attempt to save a
      limb versus perform an amputation.

PMID- 22381513
TI  - Disliked food acting as a contaminant in a sample of young children.
AB  - Anecdotal evidence suggests that a disliked food can act as a contaminant to
      liked food during childhood. While this has been investigated in an infant
      sample, the current paper presents the first study to investigate this phenomenon
      in a sample of young children (4 years 5 months-6 years 1 month old, N=30).
      Children were shown a liked food at different stages of being contaminated by a
      disliked food. At each stage, the children were asked to rate their willingness
      to consume the liked food on a 3-point hedonic scale. The data show that children
      reduce their rating of a liked food once it has been in contact with a disliked
      food, in comparison to a like-like combination control measure. The data also
      show that girls show greater sensitivity than boys to this form of contamination
      and that the younger children are more likely to show a prolonged response
      (rating of the liked food does not return to the unadulterated level) than the
      older children in the sample. Several possible reasons for these findings are
      discussed including disgust, inferred distaste and associational contamination.

PMID- 22381514
TI  - The personality trait self-directedness predicts the amygdala's reaction to
      appetizing cues in fMRI.
AB  - Personality and neural response to food cues in various mesolimbic brain
      structures have been linked to eating disorders. We investigated the question of
      whether personality traits in healthy individuals correlate with the brain
      activation induced on confrontation with appetizing visual stimuli. Personality
      was assessed in 27 normal-weight participants (14 women, mean age=26.0, SD=3.3
      years) with the Temperament and Character Inventory (TCI). After an overnight
      fast, participants viewed blocks of pictures, half containing appetizing food and
      the other half showing scrambled pictures as control. After each block,
      participants rated their appetite. Brain activation was measured using a 3T MR
      scanner. Food compared to control stimuli elicited a significantly higher
      appetite rating, as well as strong activation in the ventral and dorsal visual
      stream, the fusiform gyrus and consecutive limbic centres such as the
      parahippocampal gyrus, the amygdala, the thalamus, the insula, the ventral
      striatum and the orbitofrontal cortex. In a region-of-interest analysis, the TCI
      trait self-directedness was negatively correlated with mean blood oxygenation
      level dependent (BOLD) signal change in the right amygdala (r=-.43, p=.025).
      Ultimately, amygdala reactivity might provide a risk factor for the development
      of eating disorders.

PMID- 22381515
TI  - The transcriptome of cerebral ischemia.
AB  - The molecular causality and response to stroke is complex. Yet, much of the
      literature examining the molecular response to stroke has focused on targeted
      pathways that have been well-characterized. Consequently, our understanding of
      stroke pathophysiology has made little progress by way of clinical therapeutics
      since tissue plasminogen activator was approved for treatment nearly a decade
      ago. The lack of clinical translation is in part due to neuron-focused studies,
      preclinical models of cerebral ischemia and the paradoxical nature of neuro
      inflammation. With the evolution of the Stroke Therapy Academic Industry
      Roundtable criteria streamlining research efforts and broad availability of
      genomic technologies, the ability to decipher the molecular fingerprint of
      ischemic stroke is on the horizon. This review highlights preclinical microarray
      findings of the ischemic brain, discusses the transcriptome of cerebral
      preconditioning and emphasizes the importance of further characterizing the role
      of the neurovascular unit and peripheral white blood cells in mediating stroke
      damage and repair within the penumbra.

PMID- 22381517
TI  - Prospective outcome assessment of the therapeutic benefits of arthroscopy and
      arthrocentesis of the temporomandibular joint.
AB  - Patients who fail to respond to routine conservative measures to treat pain,
      restriction, and locking in the temporomandibular joint (TMJ) may have
      therapeutic arthroscopy or arthrocentesis, both of which are associated with
      symptomatic improvement in 86% of patients. To our knowledge there are no current
      data on improvements in mouth opening and lateral deviations after these
      procedures. This prospective audit includes 244 patients treated between 2005 and
      2010 from one surgeon's practice, who were followed up at least once at 6 weeks
      after arthroscopy or arthrocentesis. They had various conditions but all had
      tender joints. Measurements of interincisal opening, left and right lateral
      excursions, and protrusion were taken before and during operation with callipers
      (mm). Opening and pain scores were also recorded on 10 cm analogue scales before
      operation and at 6 weeks. Pain scores improved with intervention from a mean
      score of 37.1-16.1 (range 0-100). The improvement in mouth opening ranged from 0
      to 78% (as some patients had locking or pain with normal opening before
      operation), and 86% had improved enough to be discharged at 6 weeks. Temporary
      forehead weakness in two patients resolved within the timescale of the study. The
      study shows improvements in mouth opening, and confirms that pain scores can be
      improved after arthroscopy or arthrocentesis when conservative approaches have
      failed. In the hands of a skilled practitioner, arthroscopy can be a useful
      diagnostic and therapeutic adjunct, which can be used repeatedly with low
      morbidity.

PMID- 22381518
TI  - Nanostructure and crystallography of aberrant columnar vaterite in Corbicula
      fluminea (Mollusca).
AB  - Both the crystallographic and nanostructural organisation of aberrant columnar
      vaterite occurring in Corbicula fluminea were characterised in detail for the
      first time using electron microscopic and X-ray powder diffraction techniques. At
      the millimetre scale, only a confinement of the otherwise randomly oriented c
      axis to the growth surface is observed. Domains of 100 or more individual
      vaterite columns with common c-axis orientation exist within this disordered
      material. Each column behaves as a single crystal on the scale of EBSD
      measurements, but is internally composed of smaller irregularly shaped and
      slightly misaligned crystalline units (0.3-1.3MUm in dimension). These are in
      turn partitioned by porous boundaries into rounded nanodomains, up to 600nm in
      size. The geometry of the nanodomains and their respective boundaries might
      suggest formation by the accretion of vesicles. In addition to crystallographic
      textures, this observation indicates formation under significant biological
      control with wider implications for possible causes of the condition.

PMID- 22381519
TI  - Decreased expression of homeostatic chemokine receptors in intravascular large B
      cell lymphoma.

PMID- 22381520
TI  - Annual intakes of (226)Ra, (228)Ra and (40)K in staple foodstuffs from a high
      background radiation area in the southwest region of Cameroon.
AB  - Concentrations of naturally occurring radionuclides (226)Ra, (228)Ra and (40)K
      were determined in five most consumed vegetables in a high-level background
      radiation area (HLBRA) in the southwest region of Cameroon. A total of 25
      foodstuff samples collected from Akongo, Ngombas, Awanda, Bikoue and Lolodorf
      rural districts were analyzed by gamma spectrometry. The average activity
      concentration values of (226)Ra, (228)Ra and (40)K were respectively 2.30, 1.50
      and 140.40 Bq kg(-1) fresh-weights. The effective dose for individual consumption
      of the investigated foodstuff types was calculated on an estimated annual intake
      of such diets in the study area. The estimated total daily effective doses from
      the ingestion of the investigated foodstuffs for each studied long-life natural
      radionuclide were respectively 0.41 MUSv for (226)Ra, 0.84 MUSv for (228)Ra and
      0.71 MUSv for (40)K. The total annual effective dose was estimated at 0.70 mSv y(
      1). (228)Ra (44%) and (40)K (36%) were found to be the main sources for internal
      irradiation which is very likely due to the specific uptake of these
      radionuclides by the studied plants.

PMID- 22381521
TI  - Developing a summary hospital mortality index: retrospective analysis in English
      hospitals over five years.
AB  - OBJECTIVES: To develop a transparent and reproducible measure for hospitals that
      can indicate when deaths in hospital or within 30 days of discharge are high
      relative to other hospitals, given the characteristics of the patients in that
      hospital, and to investigate those factors that have the greatest effect in
      changing the rank of a hospital, whether interactions exist between those
      factors, and the stability of the measure over time. DESIGN: Retrospective cross
      sectional study of admissions to English hospitals. SETTING: Hospital episode
      statistics for England from 1 April 2005 to 30 September 2010, with linked
      mortality data from the Office for National Statistics. PARTICIPANTS: 36.5
      million completed hospital admissions in 146 general and 72 specialist trusts.
      MAIN OUTCOME MEASURES: Deaths within hospital or within 30 days of discharge from
      hospital. RESULTS: The predictors that were used in the final model comprised
      admission diagnosis, age, sex, type of admission, and comorbidity. The percentage
      of people admitted who died in hospital or within 30 days of discharge was 4.2%
      for males and 4.5% for females. Emergency admissions comprised 75% of all
      admissions and 5.5% died, in contrast to 0.8% who died after an elective
      admission. The percentage who died with a Charlson comorbidity score of 0 was 2%
      in contrast with 15% who died with a score greater than 5. Given these variables,
      the relative standardised mortality rates of the hospitals were not noticeably
      changed by adjusting for the area level deprivation and number of previous
      emergency visits to hospital. There was little evidence that including
      interaction terms changed the relative values by any great amount. Using these
      predictors the summary hospital mortality index (SHMI) was derived. For 2007/8
      the model had a C statistic of 0.911 and accounted for 81% of the variability of
      between hospital mortality. A random effects funnel plot was used to identify
      outlying hospitals. The outliers from the SHMI over the period 2005-10 have
      previously been identified using other mortality indicators. CONCLUSION: The SHMI
      is a relatively simple tool that can be used in conjunction with other
      information to identify hospitals that may need further investigation.

PMID- 22381522
TI  - Improving the experience of care for adults using NHS mental health services:
      summary of NICE guidance.

PMID- 22381523
TI  - Mood disorder in the perinatal period.

PMID- 22381524
TI  - A woman with ketoacidosis but not diabetes.

PMID- 22381525
TI  - Media induced anti-vaccination sentiment can even affect health workers, vaccine
      researcher says.

PMID- 22381526
TI  - Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix
      associated fibrin-driven inflammation coupled to the alphaMbeta2 leukocyte
      integrin receptor.
AB  - In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing
      extracellular matrix (ECM) within inflamed muscle promotes damage and
      dysfunction. However, the molecular determinants of the ECM that mediate
      inflammatory changes and faulty tissue reorganization remain poorly defined.
      Here, we show that fibrin deposition is a conspicuous consequence of muscle
      vascular damage in dystrophic muscles of DMD patients and mdx mice and that
      elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These
      benefits appear to be tied to: (i) a decrease in leukocyte integrin
      alpha(M)beta(2)-mediated proinflammatory programs, thereby attenuating
      counterproductive inflammation and muscle degeneration; and (ii) a release of
      satellite cells from persistent inhibitory signals, thereby promoting
      regeneration. Remarkably, Fib-gamma(390-396A) (Fibgamma(390-396A)) mice
      expressing a mutant form of fibrinogen with normal clotting function, but lacking
      the alpha(M)beta(2) binding motif, ameliorated dystrophic pathology. Delivery of
      a fibrinogen/alpha(M)beta(2) blocking peptide was similarly beneficial.
      Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and
      degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives
      dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)
      alpha(M)beta(2) interactions may provide a novel strategy for DMD treatment.

PMID- 22381527
TI  - Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations
      in other Usher I genes.
AB  - Inherited hearing loss in mice has contributed substantially to our understanding
      of inner-ear function. We identified a new allele at the Myo7a locus, Myo7a(sh1
      8J); genomic characterization indicated that Myo7a(sh1-8J) arose from complex
      deletion encompassing exons 38-40 and 42-46. Homozygous mutant mice had no
      detectable auditory brainstem response, displayed highly disorganized hair-cell
      stereocilia and had no detectable MYO7A protein. We generated mice that were
      digenic heterozygotes for Myo7a(sh1-8J) and one of each Cdh23(v-2J), Ush1g(js) or
      Pcdh15(av-3J) alleles, or an Ush1c null allele. Significant levels of age-related
      hearing loss were detected in +/Myo7a(sh1-8J) +/Ush1g(js), +/Myo7a(sh1-8J)
      +/Cdh23(v-2J) and +/Myo7a(sh1-8J) +/Pcdh15(av-3J) double heterozygous mice
      compared with age-matched single heterozygous animals, suggesting epistasis
      between Myo7a and each of the three loci. +/Pcdh15(av-3J) +/Ush1g(js) double
      heterozygous mice also showed elevated hearing loss, suggesting Pcdh15-Ush1g
      epistasis. While we readily detected MYO7A, USH1C, CDH23 and PCDH15 using mass
      spectrometry of purified chick utricle hair bundles, we did not detect USH1G.
      Consistent with that observation, Ush1g microarray signals were much lower in
      chick cochlea than those of Myo7a, Ush1c, Cdh23 and Pcdh15 and were not detected
      in the chick utricle. These experiments confirm the importance of MYO7A for the
      development and maintenance of bundle function and support the suggestion that
      MYO7A, USH1G (Sans) and CDH23 form the upper tip-link complex in adult mice,
      likely in combination with USH1C (harmonin). MYO7A, USH1G and PCDH15 may form
      another complex in stereocilia. USH1G may be a limiting factor in both complexes.

PMID- 22381528
TI  - Endoscopic mucosal resection with an over-the-counter hyaluronate preparation.
AB  - BACKGROUND: Hyaluronic acid (HA) provides a long-lasting and distinct mucosal
      elevation for EMR, but expense and inconvenience have limited its adoption.
      OBJECTIVE: To evaluate the safety and efficacy of an over-the-counter 0.15% HA
      preparation for EMR. DESIGN: Retrospective study. SETTING: Veterans
      Administration Hospital and university hospital. PATIENTS: 30 patients with a
      total of 32 colonic lesions and 1 duodenal lesion. INTERVENTION: EMR by using HA.
      MAIN OUTCOME MEASUREMENTS: En bloc resection rate and complications. RESULTS: EMR
      was successful in all cases. En bloc resection was achieved in 26 of the 28
      lesions up to 25 mm in diameter. Two lesions, both with fibrosis from prior
      attempted resection, had trace residual tissue necessitating cauterization with
      argon plasma. Five lesions measuring 30 mm to 60 mm all required piecemeal
      resection. There was one complication, a postpolypectomy bleed. LIMITATIONS:
      Small number of patients and retrospective design. CONCLUSIONS: EMR may be
      performed safely and effectively by using an inexpensive, over-the-counter 0.15%
      HA preparation. Further studies are needed to verify the results of this study
      and to compare the safety and efficacy of this HA preparation with saline
      solution.

PMID- 22381529
TI  - Circumferential location predicts the risk of high-grade dysplasia and early
      adenocarcinoma in short-segment Barrett's esophagus.
AB  - BACKGROUND: Whether early Barrett's neoplasia has a predilection for particular
      spatial locations in shorter segment disease is currently unknown. Anatomic
      factors may play a role in lesion location because of differing levels of mucosal
      acid exposure. OBJECTIVE: To identify high-risk lesion locations, which has
      important implications for surveillance strategies. DESIGN: We interrogated a
      prospectively maintained database of patients who underwent endoscopic resection
      (ER) for Barrett's neoplasia at 2 Australian tertiary centers. Lesions targeted
      for ER were characterized and their location in the distal esophagus was noted as
      on a clock face. A Z test of proportions was used to test for deviation from
      uniformity in the distribution of lesions. SETTING: Two Australian tertiary
      centers. PATIENTS: Patients who underwent ER for Barrett's neoplasia. MAIN
      OUTCOME MEASUREMENTS: Lesion location in the distal oesophagus, resected specimen
      histology. RESULTS: A total of 146 consecutive patients had ER for biopsy-proven
      high-grade dysplasia or esophageal adenocarcinoma. A total of 75 patients had
      Barrett's segment length of 5 cm or less and a visible lesion. Five patients had
      2 visible lesions giving a total of 80 lesions. ER of 66 lesions (82.5%) led to
      the identification of advanced pathology: 37 high-grade dysplasia (46%), 24
      mucosal adenocarcinoma (30%), 5 submucosal adenocarcinoma (6%). Of a total of 80
      lesions, 43 (53.8%) (95% CI, 42.9%-64.7%) were centered within the 2- to 5
      o'clock arc, comprising 25% of the circumference. This area also accounted for 36
      (54.5%) of the 66 lesions with advanced histology (95% CI, 42.5%-66.5%). All
      confidence intervals lie wholly above the 25% expected in a uniform circular
      distribution (P < .05). LIMITATIONS: Observational study in a tertiary center.
      CONCLUSIONS: In Barrett's maximal segments of 5 cm or less, the 2- to 5-o'clock
      arc, accounts for approximately 50% of macroscopically visible lesions and
      associated early neoplasia. This finding has important implications for
      surveillance strategies.

PMID- 22381530
TI  - Prospective, randomized, back-to-back trial evaluating the usefulness of i-SCAN
      in screening colonoscopy.
AB  - BACKGROUND: The newly developed i-SCAN application can theoretically maximize the
      effectiveness of colonoscopy. However, the practical usefulness of the i-SCAN
      application during screening colonoscopy has not been assessed. OBJECTIVE: To
      assess the efficacy of the i-SCAN application during screening colonoscopy.
      DESIGN: A prospective, randomized trial that used a modified, back-to-back
      colonoscopy. SETTING: Academic hospital. PATIENTS: This study involved 389
      asymptomatic, consecutive, average-risk patients who underwent screening
      colonoscopy. INTERVENTION: The patients were randomized to the first withdrawal
      with either conventional high-definition white light (HDWL group; n = 119), i
      SCAN contrast/surface enhancement (CE/SE) mode (i-SCAN1 group; n = 115), or i
      SCAN CE/SE/tone enhancement-colorectal mode (i-SCAN2 group; n = 118). All
      patients underwent a second examination with HDWL as the criterion standard. MAIN
      OUTCOME MEASUREMENTS: The primary outcome measurement was the adenoma detection
      rate and adenoma miss rate. The secondary outcome measurement was the accuracy of
      the histologic prediction of neoplastic and nonneoplastic polyps. RESULTS: The
      adenoma detection rates during the first withdrawal of HDWL, i-SCAN1, and i-SCAN2
      were 31.9%, 36.5%, and 33.1%, respectively (P = .742), and the adenoma miss rates
      of each group were 22.9%, 19.3%, and 15.9%, respectively (P = .513). Based on the
      multivariate analysis, the application of i-SCAN was not associated with an
      improvement in adenoma detection and the prevention of missed polyps. However,
      the prediction of neoplastic and nonneoplastic colorectal lesions was more
      precise in the i-SCAN2 group compared with the HDWL group (accuracy 79.3% vs
      75.5%, P = .029; sensitivity 86.5% vs 72.6%, P = .020; and specificity 91.4% vs
      80.6%, P = .040). LIMITATIONS: Single-center trial. CONCLUSION: i-SCAN during the
      screening colonoscopy may fail to improve adenoma detection and the prevention of
      missed polyps, but i-SCAN appears to be effective for real-time histologic
      prediction of polyps compared with conventional HDWL colonoscopy. ( CLINICAL
      TRIAL REGISTRATION NUMBER: NCT01417611.).

PMID- 22381531
TI  - Prevalence of missed adenomas in patients with inadequate bowel preparation on
      screening colonoscopy.
AB  - BACKGROUND: The prevalence of missed polyps in patients with inadequate bowel
      preparation on screening colonoscopy is unknown. OBJECTIVE: To determine the
      prevalence of missed adenomas in average-risk patients presenting for screening
      colonoscopy who are found to have inadequate bowel preparation. DESIGN:
      Retrospective chart review. Endoscopy and pathology reports were examined to
      determine the characteristics of polyps. Data from repeat colonoscopies were
      collected through 2010. SETTING: Outpatient endoscopy center at an academic
      medical center. PATIENTS: This study involved patients who underwent outpatient
      average-risk screening colonoscopy between 2004 and 2009 documented to have
      inadequate bowel preparation and who had colonoscopy to the cecum. MAIN OUTCOME
      MEASUREMENTS: Initial adenoma detection rate and adenoma detection rate on follow
      up examination. RESULTS: Inadequate bowel preparation was reported on 373
      patients, with an initial adenoma detection rate of 25.7%. Of 133 patients who
      underwent repeat colonoscopy, 33.8% had at least 1 adenoma detected, and 18.0%
      had high-risk states detected (>= 3 adenomas, 1 adenoma >= 1 cm, or any adenoma
      with villous features or high-grade dysplasia). Per-adenoma miss rate was 47.9%.
      Among patients with at least 1 adenoma on repeat colonoscopy, 31.1% had no polyps
      on initial colonoscopy; mean time between colonoscopies was 340 days. Among
      patients with high-risk states, 25.0% had no polyps seen on initial colonoscopy;
      mean time between colonoscopies was 271 days. LIMITATIONS: Retrospective design.
      CONCLUSION: Adenomas and high-risk lesions were frequently detected on repeat
      colonoscopy in patients with inadequate bowel preparation on initial screening
      colonoscopy, suggesting that these lesions were likely missed on initial
      colonoscopy.

PMID- 22381532
TI  - Randomized trial of standard versus magnetic endoscope imaging colonoscopes for
      unsedated colonoscopy.
AB  - BACKGROUND: Unsedated colonoscopy has potential benefits, including decreased
      costs and decreased risks. OBJECTIVE: To determine whether patient comfort during
      unsedated colonoscopy can be improved through the use of a magnetic endoscopic
      imaging (MEI) colonoscope compared with a standard colonoscope. DESIGN:
      Prospective, patient-blinded, randomized, controlled trial. SETTING: San
      Francisco Veterans Affairs Medical Center. PATIENTS: Veterans undergoing
      outpatient screening or surveillance colonoscopy. INTERVENTIONS: Use of a
      standard or MEI colonoscope during unsedated colonoscopy. MAIN OUTCOME
      MEASUREMENT: The primary outcome variable was patient perception of pain using a
      7-point scale. The secondary endpoint was patient willingness to undergo a future
      unsedated colonoscopy. RESULTS: Of the 160 patients enrolled, 140 completed an
      unsedated colonoscopy in the study protocol. In a per-protocol analysis, the mean
      and median pain score was 3.12 (standard deviation 1.22) and 4 (interquartile
      range 2-4) for the standard colonoscope group and 3.06 (standard deviation 1.13)
      and 3 (interquartile range 2-4) for the MEI group, where 3 was mild pain (P = not
      significant). Overall, 80% of subjects were willing to undergo a future unsedated
      colonoscopy for screening or surveillance. In an intention-to-treat analysis, 80%
      of subjects (64/80) in the standard colonoscope arm and 79% in the MEI arm
      (63/80) were willing to undergo a future unsedated colonoscopy (P = not
      significant). LIMITATIONS: Single-center study of mostly male veterans.
      CONCLUSIONS: This patient-blinded, randomized, controlled trial did not
      demonstrate any difference in patient perception of pain or willingness to
      undergo unsedated examinations when using the MEI versus the conventional
      colonoscope. Unsedated colonoscopy is generally feasible and well tolerated and
      is associated with high patient satisfaction rates.

PMID- 22381533
TI  - Left atrial appendage ligation with single transthoracic port assistance: a study
      of survival assessment in a porcine model (with videos).
AB  - BACKGROUND: Left atrial appendage (LAA) exclusion is a well-known procedure for
      the prevention of stroke in high-risk patients with atrial fibrillation and
      contraindication to long-term oral anticoagulant therapy. OBJECTIVE: To evaluate
      a natural orifice transluminal endoscopic surgery (NOTES) approach for LAA
      ligation. DESIGN: In 4 acute and 6 survival pigs, we performed LAA by using a
      forward-viewing, single-channel gastroscope and an operative thoracoscope with a
      3-mm working channel (introduced through an 8-mm single transthoracic port).
      SETTING: Animal laboratory. INTERVENTIONS: The gastroscope was introduced in the
      thoracic cavity through an esophageal submucosal tunnel. An end loop introduced
      through the gastroscope was used to legate the LAA. In the survival experiments,
      the esophageal mucosa was closed using hemoclips. MAIN OUTCOME MEASUREMENTS: The
      time, safety, and feasibility of the procedure were recorded. In the survival
      experiments, endoscopy and postmortem examination were performed on postoperative
      day 14. RESULTS: Creation of a submucosal tunnel and esophagotomy were safely
      performed in all animals without incidents. The mean time for esophagotomy was
      17.0 +/- 6.3 minutes. Pericardial dissection and LAA ligation were performed in
      all animals but 1. The mean time for LAA ligation was 34.4 +/- 19.1 minutes. No
      adverse events occurred during the survival period. Endoscopy showed complete
      esophageal closure. Postmortem examination revealed pleural adhesions on the site
      of pericardial dissection, and the LAA was fibrotic with the endoloop in place.
      LIMITATIONS: Animal study. CONCLUSIONS: LAA ligation with single transthoracic
      trocar assistance is feasible and may be an alternative to anticoagulant therapy
      or to permanent intracardiac implants in patients with atrial fibrillation.

PMID- 22381534
TI  - Self-reports of eating quickly are related to a decreased number of chews until
      first swallow, total number of chews, and total duration of chewing in young
      people.
AB  - OBJECTIVE: The validity of a self-questionnaire about eating quickly remains
      unclear. If a significant relationship between subjective and objective methods
      to evaluate eating quickly can be confirmed, then the subjective method can be
      widely and reliably used in many fields. This study investigated relationships
      between subjective and objective methods to evaluate eating quickly and also
      numerically characterized the kinesis of eating quickly in young people. DESIGN:
      One hundred and thirteen students (44 males and 69 females; mean age 22.8 +/- 2.0
      years) were selected. All subjects completed written questionnaires, and number
      of chews until first swallow, total duration of chewing, number of chews, chewing
      rate and bite size were measured using test products (a Japanese cracker and rice
      ball). RESULTS: Both male and female subjects who reported eating quickly showed
      a significantly lower number of chews until first swallow (Japanese cracker), a
      lower number of chews overall (rice ball), and a shorter total duration of
      chewing (rice ball) than other subjects. There was no difference in chewing rate
      between subjects who ate quickly or not. CONCLUSIONS: These findings suggest that
      using test products, self-reports of eating quickly are related to a decreased
      number of chews until first swallow, total number of chews, and total duration of
      chewing, but not chewing rate, and that a self-reported questionnaire to evaluate
      eating rate is valid in young people.

PMID- 22381535
TI  - Genetic polymorphisms of the sortase A gene and early childhood caries in two
      year-old children.
AB  - OBJECTIVE: To explore and compare the genetic polymorphisms of the sortase A
      (srtA) gene found in Streptococcus mutans (S. mutans) infecting two-year-old
      children suffering early childhood caries to those found in caries-free children
      through molecular identification methods. METHODS: Clinical S. mutans strains
      were isolated from the dental plaques of two-year-old children. Fifteen strains
      of S. mutans from the caries-active group and 15 strains of S. mutans from the
      caries-free group were collected. Genomic DNA was extracted from the S. mutans
      isolates. DNA fragments, including the srtA gene, were amplified by PCR. The PCR
      products were purified, sequenced and analyzed. A chi-square test and BioEdit
      software were used to analyze the sequencing results. RESULTS: All 30 clinically
      isolated S. mutans strains had a 741 base pair (bp) srtA gene. There were no
      nucleotide sequence insertions or deletions observed in the srtA genes. Twenty
      mutations were identified in the srtA genes that taken from the 30 clinical
      strains. There were 10 silent point mutations at the 78, 99, 150, 165, 186, 222,
      249, 261, 312, and 636bp positions. The other 10 mutations were point mutations
      resulting in a missense mutation at the 23, 34, 36, 47, 112, 114, 168, 176, 470,
      and 671bp positions. None of the positions were enzyme-activity sites of srt A.
      The missense mutation rates of the two groups did not exhibit statistically
      significant differences. CONCLUSION: There were no genetic polymorphisms of the
      sortase A gene associated with early childhood caries in two-year-old children.

PMID- 22381536
TI  - Syncytin 1 in the human placenta.
AB  - This study characterises HERV-W (syncytin 1) expression in normal and pathologic
      placenta and in BeWo cells. HERV-W mRNA levels were higher in the first trimester
      than at term, and similar patterns were observed with another retrovirally
      derived mRNA species, ERV-3. N-glycosylated syncytin 1 precursor (73 kDa) is
      cleaved to surface-associated (SU) and transmembrane (TM) subunits. Both were
      evident in villous trophoblast, where perinuclear and punctate cytoplasmic
      deposits were observed, and linear TM subunit immunoreactivity was seen at the
      syncytial microvillous membrane. Punctate immunoreactivity was seen in BeWo cells
      with antibodies to SU and TM, and the two were co-localised. SU immunoreactivity
      was observed in association with fetal endothelium, and this effect was increased
      in tissue from pre-eclamptic placentas, which also showed a higher level of total
      SU protein. Absence of the TM subunit from endothelium suggests it is not a
      biosynthetic source. We suggest that SU is released from trophoblast into fetal
      circulation where it may bind vascular endothelium.

PMID- 22381537
TI  - Invasions in heterogeneous habitats in the presence of advection.
AB  - We investigate invasions from a biological reservoir to an initially empty,
      heterogeneous habitat in the presence of advection. The habitat consists of a
      periodic alternation of favorable and unfavorable patches. In the latter the
      population dies at fixed rate. In the former it grows either with the logistic or
      with an Allee effect type dynamics, where the population has to overcome a
      threshold to grow. We study the conditions for successful invasions and the speed
      of the invasion process, which is numerically and analytically investigated in
      several limits. Generically advection enhances the downstream invasion speed but
      decreases the population size of the invading species, and can even inhibit the
      invasion process. Remarkably, however, the rate of population increase, which
      quantifies the invasion efficiency, is maximized by an optimal advection
      velocity. In models with Allee effect, differently from the logistic case, above
      a critical unfavorable patch size the population localizes in a favorable patch,
      being unable to invade the habitat. However, we show that advection, when intense
      enough, may activate the invasion process.

PMID- 22381538
TI  - A mathematical model of the process of ligament repair: effect of cold therapy
      and mechanical stress.
AB  - This article proposes a mathematical model that predicts the wound healing
      process of the ligament after a sprain, grade II. The model describes the
      swelling, expression of the platelet-derived growth factor (PDGF), formation and
      migration of fibroblasts into the injury area and the expression of collagen
      fibers. Additionally, the model can predict the effect of ice treatment in
      reducing inflammation and the action of mechanical stress in the process of
      remodeling of collagen fibers. The results obtained from computer simulation show
      a high concordance with the clinical data previously reported by other authors.

PMID- 22381539
TI  - A stochastic model of chromatin modification: cell population coding of winter
      memory in plants.
AB  - Biological memory, a sustained cellular response to a transient stimulus, has
      been found in many natural systems. The best example in plants is the winter
      memory by which plants can flower in favorable conditions in spring. For this
      winter memory, epigenetic regulation of FLOWERING LOCUS C (FLC), which acts as a
      floral repressor, plays a key role. Exposure to prolonged periods of cold results
      in the gradual suppression of FLC, which allows plants to measure the length of
      cold and to flower only after a sufficiently long winter. Although many genes
      involved in histone modifications have been isolated, molecular mechanisms of
      winter memory are not well understood. Here, we develop a model for chromatin
      modification, in which the dynamics of a single nucleosome are aggregated to
      on/off behavior of FLC expression at the cellular level and further integrated to
      a change of FLC expression at the whole-plant level. We propose cell-population
      coding of winter memory: each cell is described as a bistable system that shows
      heterogeneous timing of the transition from on to off in FLC expression under
      cold and measures the length of cold as the proportion of cells in the off state.
      This mechanism well explains robust FLC regulation and stable inheritance of
      winter memory after cell division in response to noisy signals. Winter memory
      lasts longer if deposition of the repressive histone mark occurs faster. A
      difference in deposition speed would discriminate between stable maintenance of
      FLC repression in annuals and transient expression in perennials.

PMID- 22381540
TI  - Pursuit of food versus pursuit of information in a Markovian perception-action
      loop model of foraging.
AB  - Efficient coding, redundancy reduction, and other information theoretic
      optimization principles have successfully explained the organization of many
      biological phenomena, from the physiology of sensory receptive fields to the
      variability of certain DNA sequence ensembles. Here we examine the hypothesis
      that behavioral strategies that are optimal for survival must necessarily involve
      efficient information processing, and ask whether there can be circumstances in
      which deliberately sacrificing some information can lead to higher utility? To
      this end, we present an analytically tractable model for a particular instance of
      a perception-action loop: a creature searching for a randomly moving food source
      confined to a 1D ring world. The model incorporates the statistical structure of
      the creature's world, the effects of the creature's actions on that structure,
      and the creature's strategic decision process. The underlying model takes the
      form of a Markov process on an infinite dimensional state space. To analyze it we
      construct an exact coarse graining that reduces the model to a Markov process on
      a finite number of "information states". This mathematical technique allows us to
      make quantitative comparisons between the performance of an information
      theoretically optimal strategy with other candidate search strategies on a food
      gathering task. We find that 1. Information optimal search does not necessarily
      optimize utility (expected food gain). 2. The rank ordering of search strategies
      by information performance does not predict their ordering by expected food
      obtained. 3. The relative advantage of different strategies depends on the
      statistical structure of the environment, in particular the variability of motion
      of the source. We conclude that there is no simple relationship between
      information and utility. Even in the absence of information processing costs or
      bandwidth constraints, behavioral optimality does not imply information
      efficiency, nor is there a simple tradeoff between the two objectives of gaining
      information about a food source versus obtaining the food itself. For a wide
      range of values of the food source's movement parameter, the strategy of
      collecting the most information possible about the unknown source location
      carries an ineliminable structural cost, leading to a situation in which a
      foraging creature could actually choose to be less well-informed while
      simultaneously being, on average, better fed.

PMID- 22381541
TI  - Steroids and microorganisms.

PMID- 22381542
TI  - Influencing safe perioperative practice through evolution.

PMID- 22381543
TI  - The influential change agent.

PMID- 22381544
TI  - Response to a quality improvement project on improving the surgical count.

PMID- 22381545
TI  - Response to a quality improvement project on improving the surgical count.

PMID- 22381548
TI  - The importance of effective communication.

PMID- 22381549
TI  - The need to be innovative.

PMID- 22381550
TI  - Nursing involvement in accountable care organizations.

PMID- 22381551
TI  - Preparing for leadership roles.

PMID- 22381552
TI  - Exploring the benefits of double gloving during surgery.
AB  - Breaches in the glove barrier pose a risk for transmission of bloodborne
      pathogens during surgical procedures. Double gloving or double gloving with an
      indicator glove system may provide added protection. For this 24-month study, we
      used a comparative design to examine the effect of double gloving with inner
      indicator gloves on the durability of inner gloves and the detection of glove
      tears or perforations during surgery. The frequency of seeing blood on the hand
      after surgery was greater with single gloving than with double gloving, and the
      frequency of changing gloves during surgery was significantly higher among those
      who double gloved with an indicator glove system versus double gloving alone. The
      majority of health care providers in our study expressed favorable views about
      double gloving.

PMID- 22381553
TI  - Comparison of current and past surgical smoke control practices.
AB  - In 2010, we teamed with AORN to repeat a simple web-based survey on surgical
      smoke control practices first conducted in 2007. This survey of AORN members
      assessed the level of compliance with established surgical smoke control measures
      (ie, use of wall suction with an in-line particulate filter, use of a smoke
      evacuator, use of an N95 or other National Institute for Occupational Safety and
      Health-approved respirator) in various medical specialties and facilities
      throughout North America, as well as the extent to which compliance rates may
      have changed since 2007. Survey responses indicate that while the use of wall
      suction as a control measure has increased for nearly all procedures, progress in
      the adoption of other control measures has been mixed, with improvement for some
      procedures, no change for most procedures, and a decrease in compliance for a few
      procedures.

PMID- 22381554
TI  - Hyperglycemia as a risk factor in the perioperative patient.
AB  - Bodily injury and stress associated with surgical interventions increase glucose
      levels not only in individuals diagnosed with diabetes mellitus but also in
      patients without a preoperative diagnosis of diabetes. Whatever the cause,
      hyperglycemia is becoming an increasingly important indicator of perioperative
      patient outcomes. An elevated blood glucose level affects the body's defense
      systems and the body's ability to heal after surgical intervention. Perioperative
      nurses should closely monitor the patient's blood glucose levels and watch for
      signs of hyperglycemia throughout the perioperative experience. Perioperative
      nurses should work collaboratively with other perioperative team members to
      identify and treat perioperative hyperglycemia.

PMID- 22381555
TI  - Safe injection practices for administration of propofol.
AB  - Sepsis and postoperative infection can occur as a result of unsafe practices in
      the administration of propofol and other injectable medications. Investigations
      of infection outbreaks have revealed the causes to be related to bacterial growth
      in or contamination of propofol and unsafe medication practices, including reuse
      of syringes on multiple patients, use of single-use medication vials for multiple
      patients, and failure to practice aseptic technique and adhere to infection
      control practices. Surveys conducted by AORN and other researchers have provided
      additional information on perioperative practices related to injectable
      medications. In 2009, the US Food and Drug Administration and the Centers for
      Disease Control and Prevention convened a group of clinicians to gain a better
      understanding of the issues related to infection outbreaks and injectable
      medications. The meeting participants proposed collecting data to persuade
      clinicians to adopt new practices, developing guiding principles for propofol
      use, and describing propofol-specific, site-specific, and practitioner-specific
      injection techniques. AORN provides resources to help perioperative nurses reduce
      the incidence of postoperative infection related to medication administration.

PMID- 22381556
TI  - Implementing AORN recommended practices for electrosurgery.
AB  - Technology is constantly changing, and it is important for perioperative nurses
      to stay current on new products and technologies in the perioperative setting.
      AORN's "Recommended practices for electrosurgery" addresses safety standards that
      all perioperative personnel should follow to minimize risks to both patients and
      staff members during the use of electrosurgical devices. Recommendations include
      how to select electrosurgical units and accessories for purchase, how to minimize
      the potential for patient and staff member injuries, what precautions to take
      during minimally invasive surgery, and how to avoid surgical smoke hazards. The
      recommendations also address education/competency, documentation, policies and
      procedures, and quality assurance/performance improvement. Perioperative nurses
      should consider the use of checklists and safety posters to remind staff members
      of the dangers of electrosurgery and the steps to take to minimize the risks for
      injury.

PMID- 22381557
TI  - Mobile health application regulations and compliance review.

PMID- 22381558
TI  - Hospital report cards: what nurses need to know.

PMID- 22381559
TI  - A people to people nursing experience: South Africa.

PMID- 22381561
TI  - "Recurrent" appendicitis.

PMID- 22381562
TI  - Fibroma of the flexor hallucis longus tendon sheath.
AB  - Fibroma of tendon sheath is a rare benign tumor that usually occurs in upper
      extremities. It is mostly asymptomatic and grows slowly within the tendons or
      tendon sheaths. Histopathologic findings show well-demarcated nodules consisting
      of haphazardly arranged fibroblast-like spindle cells, which are embedded in a
      dense, collagenous matrix. We present a patient with fibroma of the tendon sheath
      on the flexor hallucis longus tendon, which was in an unusual location and has
      never been reported. The lesion was completely excised and showed no evidence of
      recurrence after 2 years of follow-up.

PMID- 22381563
TI  - Digital image analysis versus clinical assessment of wound epithelialization: a
      validation study.
AB  - To evaluate the progress in wound healing, wound assessment is mandatory.
      Epithelialization is traditionally assessed subjectively by the clinician. In a
      previous study, subjective assessment of epithelialization was shown to be
      reliable. In this study, reliability of epithelialization measured by digital
      image analysis was investigated and then, we validated the subjective evaluation
      by comparing this assessment to measurements with digital image analysis.
      Clinicians assessed epithelialization in 50 burn wounds that were treated with a
      split skin graft. Epithelialization of these wounds was also measured by three
      observers using digital image analysis. Reliability of digital image analysis was
      tested using the intraclass correlation (IC). To test validity, subjective
      clinical assessment was correlated with digital image analysis (IC). The results
      showed that interobserver reliability of epithelialization measured by digital
      image analysis was good (IC coefficient 0.74). Subjective clinical assessment of
      epithelialization showed a strong correlation with digital image analysis (IC
      coefficient 0.80). In conclusion, subjective clinical evaluation of wound
      epithelialization is as good as an objective measure, in this study digital image
      analysis. Since digital image analysis is more time-consuming, we recommend the
      use of the subjective evaluation for daily practice.

PMID- 22381564
TI  - Brain edema and encephalopathy in acute liver failure: a primary neurogliopathy?

PMID- 22381565
TI  - Anion channels: master switches of stress responses.
AB  - During stress, plant cells activate anion channels and trigger the release of
      anions across the plasma membrane. Recently, two new gene families have been
      identified that encode major groups of anion channels. The SLAC/SLAH channels are
      characterized by slow voltage-dependent activation (S-type), whereas ALMT genes
      encode rapid-activating channels (R-type). Both S- and R-type channels are
      stimulated in guard cells by the stress hormone ABA, which leads to stomatal
      closure. Besides their role in ABA-dependent stomatal movement, anion channels
      are also activated by biotic stress factors such as microbe-associated molecular
      patterns (MAMPs). Given that anion channels occur throughout the plant kingdom,
      they are likely to serve a general function as master switches of stress
      responses.

PMID- 22381567
TI  - Proximal end clavicle fracture from a parachute jumping injury.
AB  - Fractures of the medial end of the clavicle are the least common type of clavicle
      fracture. We report a 29-year-old military parachutist who presented with medial
      end clavicle fracture after a bad landing. He was first treated non-operatively
      in a tertiary center and was then referred to our center by his general
      practitioner. Surgery was indicated since the fracture was displaced and the
      patient needed anatomical reconstruction to promote rapid bone healing and a
      prompt return to work. The medial fragment being comminuted, K-wires were used
      for internal fixation instead of a plate. The two K-wires were bent 180 degrees 
      to avoid risk of migration and were removed 3 months after surgery when the
      patient had begun to perform all activities without pain. Aggressive treatment is
      recommended for medial end clavicle fracture in case of displacement and
      facilitates rapid functional recovery, notably in patients with considerable
      clavicular demand.

PMID- 22381566
TI  - Accuracy of the preoperative planning for cementless total hip arthroplasty. A
      randomised comparison between three-dimensional computerised planning and
      conventional templating.
AB  - INTRODUCTION: A high accuracy was recently reported for the three-dimensional
      (3D) computerised planning of total hip arthroplasty (THA), comparing well with
      navigation regarding leg length and femoral offset. However, there is no
      randomised study comparing 3D preoperative planning with conventional 2D
      templating in terms of accuracy and clinical relevance. HYPOTHESIS: The 3D
      preoperative planning has a higher accuracy than the conventional 2D preoperative
      templating regarding the implants size and their positioning. PATIENTS AND
      METHODS: A prospective comparative randomised study was carried out from 2008 to
      2009, including two groups of 30 patients who underwent THA for primary
      osteoarthritis. One surgeon performed all the surgical procedures using a
      minimally invasive direct anterior approach. In one group, the planning was made
      on calibrated X-rays using 2D templates. In the other group, a CT-scan based 3D
      computerised planning was performed with dedicated software. The reconstructed
      hip final anatomy was compared postoperatively to the preoperative planning and
      the accuracy was expressed as the mean difference (+/-SD) between the planned
      positioning and the final positioning of the implants. RESULTS: The prediction
      rate for the stem and the cup sizes were respectively of 100% and 96% in the 3D
      group versus 43% for both components in the 2D group. When combining both
      components, the prediction rate was 96% in the 3D group versus 16% in the 2D
      group. In the 3D group, a high accuracy was achieved for the planning of the leg
      length (-1.8+/-3.6 mm ranging from -8 to+4mm) and the femoral offset (-0.07+/-2.7
      mm ranging from -5 to+4mm) versus 1.37+/-6.4mm ranging from -9 to 13 mm and
      0.33+/-5.7 mm (-16 to 11 mm) in the 2D templating group (P<0.0001). DISCUSSION:
      The 3D planning gives a higher accuracy than conventional 2D templating in
      forecasting the size of cup and the stem. This contributes to the prediction for
      leg length and offset that is more reliable with the 3D technique. This study
      suggests that 3D planning CT-scan data is an attractive alternative to navigation
      to restore these parameters. The high accuracy achieved by a low-experience
      surgeon suggests that 3D planning may help shorten the learning curve when using
      the minimally invasive direct anterior approach. LEVEL OF EVIDENCE: Level III low
      powered prospective randomized trial.

PMID- 22381568
TI  - Distal partial ruptures of triceps brachii tendon in an athlete.
AB  - Distal brachii triceps tendon rupture is rare. Partial lesions are not so well
      defined. If functionally they are well tolerated in patients with low functional
      demand, management guideline is not so clear for sportsmen. To our best
      knowledge, there is no reported technique for the repair of partial forms. A 28
      year-old patient was operated on for a partial triceps rupture. He underwent a
      transosseous olecranon suture of the tricipital tendon, with a side-to-side
      suture to the healthy residual tendon. The patient was assessed at 2 years follow
      up with the DASH score. He had painless and mobile elbow with no effusion and
      returned to sport 4 months after his surgical repair. The extension strength was
      comparable to the healthy side (5/5). The DASH score was 1,7 for global score,
      and 6,3 for work and sport modules. Partial rupture of brachii triceps tendon is
      not well tolerated in high functional demand patients. We think that patients
      should be operated in these situations and may achieve excellent results.
      Postoperative management is crucial to achieve good results as well as in
      complete rupture.

PMID- 22381569
TI  - A novel hepcidin-like in turbot (Scophthalmus maximus L.) highly expressed after
      pathogen challenge but not after iron overload.
AB  - Hepcidins are antimicrobial peptides with an important role in the host innate
      immunity. Moreover, it has been reported that mammalian hepcidins present a dual
      function being a key regulator in the iron homeostasis. Here, we describe the
      coding sequence of a novel hepcidin-like peptide in turbot, Scophthalmus maximus.
      This molecule presents several differences with regard to the previously
      characterized hepcidin in this flatfish species and it has not the hypothetical
      iron regulatory sequence Q-S/I-H-L/I-S/A-L in the N-terminal region. Therefore we
      propose the existence of at least two types of hepcidin in turbot. Moreover,
      results revealed a higher variability in the mRNA sequences of the novel hepcidin
      compared with the other form. Constitutive expression of turbot hepcidins
      (Hepcidin-1 and Hepcidin-2) was analyzed in several tissues and as expected, both
      molecules were highly represented in liver. On the other hand, the effect of
      three different stimuli (bacterial or viral infection and iron overloading) in
      the level of hepcidin mRNA was also examined and a differential response to
      pathogens and iron was observed. Whereas both hepcidins were affected by pathogen
      challenge, only Hepcidin-1 was up-regulated after iron overloading. Therefore,
      this and other evidences suggest that these peptides could be involved in
      different functions covering the dual role of mammalian hepcidins.

PMID- 22381570
TI  - Seven cases of vitiligo complicated by atopic dermatitis: suggestive new spectrum
      of autoimmune vitiligo.

PMID- 22381571
TI  - Incidence of prostate cancer in Lithuania after introduction of the Early
      Prostate Cancer Detection Programme.
AB  - In Lithuania, prostate-specific antigen (PSA) testing is offered to healthy
      asymptomatic men as a screening test in the population-based Early Prostate
      Cancer Detection Programme (EPCDP). The aim of this study was to analyse the
      incidence of prostate cancer before and after introduction of the EPCDP in
      Lithuania. Prostate cancer incidence and mortality data from the Lithuanian
      Cancer Registry were analysed for the period 1990-2008. Age-specific incidence
      and mortality data were adjusted to the European Standard Population. There have
      been extraordinary changes in the incidence of prostate cancer in Lithuania
      following introduction of the EPCDP, and there is strong evidence that these
      changes are the result of increased detection rates, especially in men of
      screening age. Further observation of changes in prostate cancer incidence and
      mortality in Lithuania may help to determine the extent to which PSA testing at
      the population level influences incidence and mortality in the general
      population.

PMID- 22381572
TI  - Can humanization theory contribute to the philosophical debate in public health?
AB  - This paper will explore the humanization value framework for research, policy and
      practice with regard to its relevance for public health, specifically the
      reduction of inequities in health. This proposed framework introduces humanizing
      values to influence research, policy and practice. The framework is articulated
      through eight specific constituents of what it is to be human. These dimensions
      are articulated as humanizing and dehumanizing dimensions that have the potential
      to guide both research and practice. The paper will then go on to consider these
      dimensions in relation to the emergent qualities of the potential 'fifth-wave' of
      public health intervention. The humanization dimensions outlined in this paper
      were presented as emerging from Husserl's notion of lifeworld, Heidegger's
      contemplations about human freedom and being with others, and Merleau-Ponty's
      ideas about body subject and body object. Husserl's ideas about the dimensions
      that make up 'lifeworld', such as embodiment, temporality and spatiality,
      underpin the suggested dimensions of what it is to be human. They are proposed in
      the paper as together informing a value base for considering the potentially
      humanizing and dehumanizing elements in systems and interactions. It is then
      proposed that such a framework is useful when considering methods in public
      health, particularly in relation to developing new knowledge of what is both
      humanizing and dehumanizing within research and practice.

PMID- 22381573
TI  - Comparison of unilateral versus bilateral instrumented transforaminal lumbar
      interbody fusion in degenerative lumbar diseases.
AB  - BACKGROUND CONTEXT: Transforaminal lumbar interbody fusion (TLIF) has become a
      well-established technique that is traditionally performed with bilateral pedicle
      screw (PS) fixation. There are only a small number of case reports of unilateral
      instrumented TLIF. To our knowledge, there have been few well-designed studies
      comparing unilateral versus bilateral instrumentation with TLIF. PURPOSE: To
      compare clinical and radiographic outcomes in a selected series of patients
      treated with unilateral versus bilateral PS instrumented TLIF. STUDY DESIGN:
      Prospective randomized study in one unit. PATIENT SAMPLE: A total of 80 patients
      were enrolled in this study. Thirty-seven patients (17 men and 20 women; average
      age 57.1 years) were randomized to the unilateral PS group and 43 patients (18
      men and 25 women; average age 58.2 years) to the bilateral PS group. OUTCOME
      MEASURES: The demographic data collected from both groups were gender, age,
      preoperative index diagnosis, degenerated segment, and single/double level of
      fusion. Operative time, blood loss, hospital time, and implant costs were also
      evaluated. Postsurgical pain and functional results were analyzed by the visual
      analog scale (VAS), modified Prolo (mProlo) scores, and Oswestry Disability Index
      (ODI). Radiographic examinations were carried out to assess total fusion rates,
      screw failure, and general complications. METHODS: Patients were randomized into
      the unilateral or bilateral PS instrumented TLIF group based on a computer
      generated number list. Patients were asked to return to hospital for follow-up at
      4 weeks, 3 months, 6 months, 12 months, and thereafter once a year after surgery.
      RESULTS: The mean follow-up was 25.3 months, with a range of 18 to 32 months.
      There were no significant differences between the two groups in terms of
      demographic data. The unilateral PS group had a significantly shorter operative
      time, less blood loss, and reduced implant costs compared with the bilateral PS
      group, although hospital time was the same for double-level cases. The average
      postoperative VAS, mProlo, and ODI scores improved significantly in both groups,
      with no significant difference between groups. The total fusion rate, screw
      failure, and general complication rate were not significantly different.
      CONCLUSIONS: Unilateral PS instrumented TLIF is a viable treatment option
      generating better results, especially in terms of operative time, blood loss, and
      hospital time for single-level disease and implant costs. No decrease in the
      fusion rate or increase in the complication rate was observed in this group.
      Further improved study design and a longer period of follow-up are needed to
      confirm this effect.

PMID- 22381574
TI  - Effect of methodological quality measures in spinal surgery research: a
      metaepidemiological study.
AB  - BACKGROUND CONTEXT: Methodological quality measures of trials in meta-analyses
      have been shown to influence the pooled effect sizes in several medical fields.
      However, for spinal surgery, influence of quality measures has not been assessed.
      PURPOSE: The purpose of this study was to analyze the influence of quality
      measures in studies on effectiveness in spinal surgery. STUDY DESIGN: A
      metaepidemiological study was performed on meta-analyses within spinal surgery.
      METHODS: A systematic search was performed in MEDLINE, Cochrane Database, and
      EMBASE in August 2009. The effect sizes, defined as risk of positive clinical
      outcome, of trials included in the meta-analyses were assessed. The differences
      in effect sizes were calculated as risk differences (RDs). Relation of the RDs to
      potential quality measures such as sponsoring, randomization, allocation
      concealment, blinding, and study size was assessed with metaregression adjusted
      for multiple testing. RESULTS: Seven reviews consisting of 118 studies were
      included. Data provided by the systematic reviews alone were insufficient to
      analyze the effect of quality measures. Metaregression analysis of 76 of the
      individual trials reporting clinical outcome, though, showed that sample size,
      strict randomization, and outcome blinding were significant quality measures
      influencing study effect. Risk difference of effect from validly randomized
      studies was higher compared with not validly randomized and comparative
      observational trials (5.4%; 95% confidence interval [CI], 1.2-9.6; p=.044).
      Studies with adequate observer blinding showed a 7.2% lower RD (95% CI, 0.8-13.7;
      p=.049). For each increase of 100 patients, the RD decreased 3.6% (95% CI, 0.5
      6.8; p=.098). CONCLUSIONS: Contrary to basic methodological assertions, formal
      and strict randomization appeared to produce a significantly higher RD in spinal
      surgery research. Sufficient sample size and observer blinding, on the other
      hand, led to a lower RD as expected. These findings imply that effect of quality
      measures assessed in metaepidemiological studies should not be too easily
      translated to research in spinal surgery.

PMID- 22381575
TI  - High-fat-diet exposure induces IgG accumulation in hypothalamic microglia.
AB  - The mediobasal hypothalamic arcuate nucleus (ARC), with its relatively 'leaky'
      blood-brain barrier that allows more circulating molecules to enter the brain,
      has emerged as a key sensor of blood-borne signals. In both the ARC and white
      adipose tissue (WAT), consumption of a high-fat diet (HFD) rapidly induces
      infiltration of microglia (ARC) or macrophages (WAT). Animals with HFD-induced
      obesity (DIO) and insulin resistance additionally accumulate B cells in WAT,
      increasing the local production of pathogenic antibodies. We therefore
      investigated whether DIO mice or genetically obese ob/ob mice have increased IgG
      in the ARC, analogous to the recent observations in WAT. Following 16 weeks of
      exposure to a HFD, wild-type (WT) mice had significantly increased IgG
      immunoreactivity (ir) signaling that was specific to the ARC and was exclusively
      concentrated in microglia. By contrast, IgG-ir of age-matched obese ob/ob mice
      fed standard chow had ARC IgG levels comparable with those in chow-fed WT control
      mice. However, following 2 weeks of HFD exposure, ob/ob mice also had a
      significant increase of IgG-ir in the ARC. In summary, our findings reveal a
      novel pathophysiological phenomenon, specific for the hypothalamic ARC, that is
      induced by exposure to a HFD and can be enhanced, but not caused, by genetic
      obesity.

PMID- 22381576
TI  - The upper hand on compartment syndrome.
AB  - Metacarpal fractures are common injuries, accounting for approximately 30% to 40%
      of all hand fractures and with a lifetime incidence of 2.5%. Traditionally
      regarded as an innocuous injury, metacarpal fractures tend to be associated with
      successful outcomes after closed reduction and immobilization. Hand compartment
      syndrome (HCS) is a rare clinical entity with potential devastating consequences
      in terms of loss of function and quality-of-life outcomes. We discuss the case of
      a 44-year-old woman presenting with multiple closed metacarpal fractures as a
      result of low-energy trauma, complicated by acute HCS. We review the
      presentation, clinical assessment, and optimal surgical management of acute HCS
      with reference to international literature.

PMID- 22381577
TI  - Lack of efficacy of phenytoin in children presenting with febrile status
      epilepticus.
AB  - BACKGROUND: Fever is the most common precipitant of status epilepticus in
      children. Animal models suggest that only gamma-aminobutyric acidic drugs are
      effective in the treatment of febrile seizures, but there is limited clinical
      evidence to support this. OBJECTIVE: The aim of this study was to determine the
      efficacy of phenytoin, a sodium channel blocker, in the treatment of febrile
      status epilepticus in children. METHODS: This study is a retrospective chart
      review of 56 children (62 episodes) who presented to our emergency department
      with febrile status epilepticus and received phenytoin. The clinical parameters
      were evaluated by reviewing the charts. The efficacy of phenytoin was classified
      into 3 categories: positive, negative, and nonevaluable response. RESULTS: The
      primary outcome was to evaluate the efficacy rate of phenytoin; there were 9
      (14.5%) of 62 episodes with a positive response, 25 (40.3%) with a negative
      response, and 28 (45.2%) with a nonevaluable response because phenytoin was given
      simultaneously with a gamma-aminobutyric acidic (GABAergic) drug (P < .001). The
      secondary outcome was to measure the mean seizure duration for each treatment
      category, which were 52.8, 109.9, and 52.6 minutes, respectively (P < .01).
      CONCLUSION: Phenytoin is rarely effective in controlling febrile status
      epilepticus. Children exposed to phenytoin have more prolonged febrile seizures,
      increasing the risk of brain injury.

PMID- 22381578
TI  - Development and validation of the excess mortality ratio-based Emergency Severity
      Index.
AB  - PURPOSE: The purpose of this study is to develop and validate the excess
      mortality ratio-based Emergency Severity Index (EMR-ESI) that feasibly and
      objectively assesses the severity of emergency department (ED) patients based on
      their chief complaints. METHODS: We used data from the National Emergency
      Department Information System of Korea from January 2006 to December 2009. We
      obtained information on mortality and the corresponding chief complaints
      exhibited by patients presenting to all EDs. The EMR-ESI was computed from the
      ratio of sex-age standardized hospital mortality for each chief complaint and the
      sex-age standardized mortality of the entire population of Korea. We tested the
      discriminatory power of the EMR-ESI on the prediction of hospital outcomes using
      the area under the receiver operating characteristic curve (AUC) from a
      multivariate logistic regression model. This model was adjusted for clinical
      parameters, and the goodness of fit was estimated using the Hosmer-Lemeshow
      logistic model. RESULTS: Included in the study were 4 713 462 patients who
      presented 7557 chief complaint codes from 2006 to 2008. The EMR-ESI had a range
      of 0 to 6389.45 (mean +/- SD, 1.11 +/- 4.67; median, 0.70). The adjusted odds
      ratio of the EMR-ESI (unit, 1.0) for hospital mortality was 1.11 (95% confidence
      interval, 1.11-1.12). The AUCs for predicting hospital mortality, ED mortality,
      admission mortality, and admission were 0.95, 0.98, 0.90, and 0.74, respectively.
      There were 3 422 865 patients from 2009 who were included for external
      validation, and the AUCs for predicting mortality in the hospital, the ED, the
      inpatient ward, and for predicting admission were 0.95, 0.99, 0.90, and 0.75,
      respectively. CONCLUSION: The EMR-ESI was notably useful in predicting hospital
      mortality and the admission of emergency patients.

PMID- 22381579
TI  - Phases of daylight and the stability of color perception in the near peripheral
      human retina.
AB  - Typical daylight extends from blue (morning sky) to orangey red (evening sky) and
      is represented mathematically as the Daylight Locus in color space. In this
      study, we investigate the impact of this daylight variation on human color
      vision. Thirty-eight color normal human observers performed an asymmetric color
      match in the near peripheral visual field. Unique hues were identified using a
      naming paradigm. The observers' performance for matching was almost perfectly
      coincident with the Daylight Locus but declined markedly in other regions.
      Interobserver variability reached a conspicuous minimum adjacent to the Daylight
      Locus and was maximal in the red and yellowish-green regions. In the naming task,
      unique blue and yellow were virtually coincident with the Daylight Locus. The
      results suggest that the mechanisms of color perception mediated by the
      phylogenetically older (blue-yellow) color pathway have been strongly influenced
      by the different phases of daylight.

PMID- 22381580
TI  - Oxidative dissolution of polymer-coated CdSe/ZnS quantum dots under UV
      irradiation: mechanisms and kinetics.
AB  - To advance the knowledge of environmental fate of nanomaterials, we
      systematically investigated the dissolution of polymer-coated CdSe/ZnS quantum
      dots (QDs) under UV (254 nm) irradiation. The environmental effects (i.e.,
      irradiation intensity, dissolved oxygen, temperature, and humic acid), as well as
      the coating effects on dissolution kinetics of QDs were investigated. Our results
      showed that higher irradiation intensity and temperature increased ion release
      rates (Cd(2+), SeO(4)(2-), and Zn(2+)), whereas the different polymer coatings
      varied the dissolution rates. The absence of dissolved oxygen inhibited the
      dissolution of QDs, and we further demonstrated that the dissolution was a photo
      oxidative process involved superoxide radical formation. Humic acid had a twofold
      effect on dissolution due to its photosensitization and photoabsorption for UV
      irradiation. Finally, an empirical kinetic law was proposed to interpret the
      above environmental effects. This study lays groundwork to better understand the
      environmental fate of QDs.

PMID- 22381581
TI  - Comparison of unilateral versus bilateral balloon kyphoplasty for the treatment
      of osteoporotic vertebral compression fractures.
AB  - Thirty-one patients with osteoporotic vertebral compression fractures (OVCF) were
      treated with unilateral balloon kyphoplasty (BKP), and 31 patients were treated
      with bilateral BKP. The efficacy of unilateral and bilateral BKP was assessed by
      comparing operation time, X-ray exposure times, incidence of complications,
      vertebral height restoration, and improvement of the visual analogue scale (VAS)
      scores. The mean operative time and the exposure time to X-rays in the unilateral
      BKP group was less than that of the bilateral BKP group (p<0.05). No
      statistically significant differences were observed in the cement leakage rate,
      VAS score, or vertebral height restoration between the two groups (p>0.05).
      Unilateral and bilateral BKP are safe and effective treatments for OVCF. Compared
      with bilateral BKP, patients undergoing unilateral BKP have shorter operations
      and receive lower X-ray radiation doses.

PMID- 22381582
TI  - Quantitative analysis of neovascular permeability in glioma by dynamic contrast
      enhanced MR imaging.
AB  - This study was designed to quantitatively analyse neovascular permeability in
      glioma by dynamic contrast-enhanced MRI (DCE-MRI). Forty-four patients with
      glioma were included in this study. The highest value of volume transfer constant
      (K(trans)) and volume of extravascular extracellular space per unit volume of
      tissue (V(e)) were obtained and the differences in K(trans) and V(e) between low
      grade glioma (LGG) and high-grade glioma (HGG) were analyzed. The correlations
      between K(trans), V(e) and glioma grade were performed. Receiver operating
      characteristic (ROC) curve analyses were conducted. The values of K(trans) and
      V(e) of LGG were significantly lower than those of HGG. The correlation analysis
      demonstrated statistically significant relationships between K(trans) and glioma
      grade, between V(e) and glioma grade, and between K(trans) and V(e). The ROC
      curve analyses of K(trans) (0.035/min) and V(e) (0.130) for differentiating LGG
      from HGG were statistically significant. Thus, DCE-MRI can be used to estimate
      neovascular permeability and for pre-operative grading of glioma.

PMID- 22381583
TI  - Neuropeptide Y promotes neurogenesis and protection against methamphetamine
      induced toxicity in mouse dentate gyrus-derived neurosphere cultures.
AB  - Methamphetamine (METH) is a psychostimulant drug of abuse that causes severe
      brain damage. However, the mechanisms responsible for these effects are poorly
      understood, particularly regarding the impact of METH on hippocampal
      neurogenesis. Moreover, neuropeptide Y (NPY) is known to be neuroprotective under
      several pathological conditions. Here, we investigated the effect of METH on
      dentate gyrus (DG) neurogenesis, regarding cell death, proliferation and
      differentiation, as well as the role of NPY by itself and against METH-induced
      toxicity. DG-derived neurosphere cultures were used to evaluate the effect of
      METH or NPY on cell death, proliferation or neuronal differentiation. Moreover,
      the role of NPY and its receptors (Y(1), Y(2) and Y(5)) was investigated under
      conditions of METH-induced DG cell death. METH-induced cell death by both
      apoptosis and necrosis at concentrations above 10 nM, without affecting cell
      proliferation. Furthermore, at a non-toxic concentration (1 nM), METH decreased
      neuronal differentiation. NPY's protective effect was mainly due to the reduction
      of glutamate release, and it also increased DG cell proliferation and neuronal
      differentiation via Y(1) receptors. In addition, while the activation of Y(1) or
      Y(2) receptors was able to prevent METH-induced cell death, the Y(1) subtype
      alone was responsible for blocking the decrease in neuronal differentiation
      induced by the drug. Taken together, METH negatively affects DG cell viability
      and neurogenesis, and NPY is revealed to be a promising protective tool against
      the deleterious effects of METH on hippocampal neurogenesis.

PMID- 22381584
TI  - Pharmacological evidence of functional inhibitory metabotrophic glutamate
      receptors on mouse arousal-related cholinergic laterodorsal tegmental neurons.
AB  - Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) are importantly
      involved in neurobiological mechanisms governing states of arousal such as sleep
      and wakefulness as well as other appetitive behaviors, such as drug-seeking.
      Accordingly, mechanisms controlling their excitability are important to elucidate
      if we are to understand how these LDT neurons generate arousal states. Glutamate
      mediates the vast majority of excitatory synaptic transmission in the vertebrate
      CNS and while presence of glutamate input in the LDT has been shown and
      ionotropic responses to glutamate have been reported in the LDT, characterization
      of metabotropic responses is lacking. Therefore, electrophysiological responses
      and changes in levels of intracellular Ca(2+) in mouse cholinergic LDT neurons
      following application of specific mGluR agonists and antagonists were examined.
      Unexpectedly, both the mGluR(5)specific agonist, CHPG, and the group II mGluR
      (mGlu(2/3)) agonist, LY379268 (LY), induced a TTX-insensitive outward
      current/hyperpolarization. Both outward currents were significantly reduced by
      the mGluR antagonist MCPG and the CHPG-induced current was blocked by the
      specific mGluR(5) antagonist MTEP. Concurrent Ca(2+)imaging revealed that while
      CHPG actions did include release of Ca(2+) from CPA/thapsigargin-sensitive
      intracellular stores, actions of LY did not. Both CHPG- and LY-induced outward
      currents were mediated by a TEA-sensitive potassium conductance. The large
      conductance, Ca(2+)-dependent potassium (BK) channel blocker, iberiotoxin,
      attenuated CHPG actions. Consistent with actions on the BK conductance, CHPG
      enhanced the amplitude of the fast component of the after hyperpolarizing
      potential, concurrent with a reduction in the firing rate. We conclude that
      stimulation of mGluR(5) and group II (mGluR(2/3)) elicits postsynaptically
      mediated outward currents/hyperpolarizations in cholinergic LDT neurons. Effects
      of glutamatergic input would be, thus, expected not only to be excitation via
      stimulation of ionotropic glutamate receptors and mGluR(1), but also inhibition
      via actions at mGluR(5) and mGluR(2/3) on these neurons. As these two processes
      counteract each other, these surprising findings necessitate revision of
      predictions regarding the net level of excitation generated by glutamate input to
      cholinergic LDT cells and, by extension, the functional outcome of glutamate
      transmission on processes which these neurons regulate. This article is part of a
      Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22381585
TI  - Biologic rationale and clinical activity of mTOR inhibitors in gynecological
      cancer.
AB  - Advanced recurrent gynecological malignancies have a poor prognosis despite
      systemic treatment, which is usually cytotoxic chemotherapy. Responses are
      generally short-lived and more effective treatments are needed. Rationally
      designed molecularly targeted therapy is an emerging and important option in this
      setting. The mammalian target of rapamycin (mTOR) is a serine/threonine protein
      kinase of the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway with a
      critical role in controlling cancer cellular growth, metabolism and cell cycle
      progression. Aberrant PI3K-dependent signaling occurs frequently in a wide range
      of tumor types, including ovarian, endometrial and cervical cancer. Early
      clinical studies of first-generation mTOR inhibitors have shown promising
      clinical activity in endometrial cancer. However, the molecular basis of
      sensitivity and resistance to these agents remains largely unknown. In this
      review, we will update the clinical and biological data underlying the
      development of first generation mTOR inhibitors in the treatment of gynecological
      tumors. The role of potential new combination regimens with mTOR inhibitors in
      gynecological cancers will also be discussed.

PMID- 22381586
TI  - Impact of ankle osteoarthritis on the energetics and mechanics of gait: the case
      of hemophilic arthropathy.
AB  - BACKGROUND: Osteoarthritis may affect joints in any part of the body, including
      the ankle. The purpose of this study was to assess the impact of ankle
      osteoarthritis on the energetics and mechanics of gait, while taking into account
      the effect of slower speed generally adopted by patients with osteoarthritis.
      METHODS: Using a motion analysis system, synchronous kinematic, kinetics,
      spatiotemporal, mechanics and metabolic gait parameters were measured in 10
      patients diagnosed with ankle osteoarthritis consecutive to hemophilia. The
      subjects walked at a self-selected speed and their performance was compared to
      speed-matched normal values obtained in healthy control subjects. FINDINGS: Speed
      normalization using a Z-score transformation showed a significant increase in
      metabolic cost (Z=1.78; P=0.006) and decrease in mechanical work (Z=-0.97;
      P=0.009). As a consequence, muscular efficiency also decreased (Z=-0.97;
      P=0.001). These changes were associated with a surprising efficacy of the
      pendular mechanism, i.e., an improved recovery index (Z=0.97; P=0.004).
      INTERPRETATION: Our findings suggest that patients with ankle osteoarthritis
      adopt a walking strategy which improves recovery through the pendular mechanism.
      This may be a compensatory mechanism in order to economize energy which would
      counterbalance the energy waste due to low muscle efficiency. These modifications
      are proportional to the impaired ankle function. Our data provides a quantitative
      baseline to better understand the dynamics of ankle osteoarthritis and determine
      the individual role that lower limb joints play in the multiple chronic joint
      affections.

PMID- 22381587
TI  - Nonparametric Bayesian inference of the fiber orientation distribution from
      diffusion-weighted MR images.
AB  - Diffusion MR imaging provides a unique tool to probe the microgeometry of nervous
      tissue and to explore the wiring diagram of the neural connections noninvasively.
      Generally, a forward model is established to map the intra-voxel fiber
      architecture onto the observable diffusion signals, which is reformulated in this
      article by adopting a measure-theoretic approach. However, the inverse problem,
      i.e., the spherical deconvolution of the fiber orientation density from noisy MR
      measurements, is ill-posed. We propose a nonparametric representation of the
      tangential distribution of the nerve fibers in terms of a Dirichlet process
      mixture. Given a second-order approximation of the impulse response of a fiber
      segment, the specified problem is solved by Bayesian statistics under a Rician
      noise model, using an adaptive reversible jump Markov chain Monte Carlo sampler.
      The density estimation framework is demonstrated by various experiments with a
      diffusion MR dataset featuring high angular resolution, uncovering the fiber
      orientation field in the cerebral white matter of the living human brain.

PMID- 22381588
TI  - Interleukin-6 and insulin incrase and nitric oxide and adiponectin decrease in
      blind dogs with pituitary-dependent hyperadrenocorticism.
AB  - In this study, two populations of dogs with pituitary dependent hypercortisolism
      (PDH) were compared over a 2-year period. One group had normal vision (Group A,
      n=27) and one group was blind (Group B, n=20). Group B was characterised by the
      rapid appearance of the clinical signs of PDH that precede blindness. We found
      increases in pre-adrenocorticotropic hormone cortisol (P=0.002), IL-6 (P=0.0001),
      insulin, and insulin sensitivity (detected with the Homeostatic Model Assessment,
      P<0.0001) in Group B but not in Group A. The nitric oxide (NO) and the total
      adiponectin concentrations decreased (P=0.0001 and P=0.02, respectively) in Group
      B versus Group A. The IL-6 and insulin concentrations and the HOMA-A index were
      positively correlated with the cortisol concentration and were negatively
      correlated with the NO concentration. With the exception of adiponectin, the
      other variables were associated with blindness. We concluded that blindness in
      PDH is a haemodynamic event associated with metabolic changes, with the increase
      in the IL-6 concentration and the decrease in the NO concentration affecting the
      retinal vasculature and producing a high risk of vision loss.

PMID- 22381589
TI  - Subepidermal blistering disease presenting with anti-plakin antibodies.

PMID- 22381591
TI  - Hunter Holmes McGuire: much more than Stonewall Jackson's surgeon.

PMID- 22381590
TI  - Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL.
AB  - The precise regulation of phosphoinositide lipids in cellular membranes is
      crucial for cellular survival and function. Inositol 5-phosphatases have been
      implicated in a variety of disorders, including various cancers, obesity, type 2
      diabetes, neurodegenerative diseases and rare genetic conditions. Despite the
      obvious impact on human health, relatively little structural and biochemical
      information is available for this family. Here, we review recent structural and
      mechanistic work on the 5-phosphatases with a focus on OCRL, whose loss of
      function results in oculocerebrorenal syndrome of Lowe and Dent 2 disease.
      Studies of OCRL emphasize how the actions of 5-phosphatases rely on both
      intrinsic and extrinsic membrane recognition properties for full catalytic
      function. Additionally, structural analysis of missense mutations in the
      catalytic domain of OCRL provides insight into the phenotypic heterogeneity
      observed in Lowe syndrome and Dent disease.

PMID- 22381592
TI  - Permissive hypercapnia in the management of congenital diaphragmatic hernia: our
      institutional experience.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially lethal anomaly
      associated with pulmonary hypoplasia and persistent pulmonary hypertension.
      Permissive hypercapnia is a strategy designed to reduce lung injury from
      mechanical ventilation in infants. It has been shown to be a potentially superior
      method of ventilator management for patients with CDH. In 2001, the Divisions of
      Neonatology and Pediatric Surgery at the University of Virginia Children's
      Hospital established permissive hypercapnia as the management strategy for
      treatment of CDH. We hypothesized that permissive hypercapnia would be associated
      with improved outcomes in this patient population. STUDY DESIGN: This
      retrospective review compares outcomes of infants treated for CDH in the
      extracorporeal membrane oxygenation (ECMO) era before and after initiation of
      permissive hypercapnia at a single institution. Outcomes were compared using
      univariate statistical analysis. RESULTS: Ninety-one patients were available for
      analysis and were divided into 2 groups: 42 (Group 1) treated before and 49
      (Group 2) treated after implementation of permissive hypercapnia. Survival was
      higher in Group 2 (85.8% vs 54.8%; p = 0.001; relative risk [RR] 3.17). Morbidity
      was lower in Group 2 and approached statistical significance (65.3% vs 83.3%; p =
      0.052). Patients in Group 2 were repaired later, had a lower rate of ECMO use,
      and were extubated earlier. There was no difference in hospital stay.
      CONCLUSIONS: The use of permissive hypercapnia for infants with CDH was
      associated with decreased mortality, a longer period of ventilation before repair
      with a shorter period of ventilation after repair, a lower rate of ECMO use, and
      no lengthening of hospital stay. Permissive hypercapnia remains the standard of
      care for ventilation of infants with CDH at our institution.

PMID- 22381593
TI  - Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as
      electrophysiological signatures of BOLD resting state networks.
AB  - Neuroimaging research suggests that the resting cerebral physiology is
      characterized by complex patterns of neuronal activity in widely distributed
      functional networks. As studied using functional magnetic resonance imaging
      (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain
      activity is associated with slowly fluctuating hemodynamic signals (~10s). More
      recently, multimodal functional imaging studies involving simultaneous
      acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested
      that the relatively slow hemodynamic fluctuations of some resting state networks
      (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient
      brain states reflected in EEG signals, that are referred to as "microstates". To
      further elucidate the relationship between microstates and RSNs, we developed a
      fully data-driven approach that combines information from simultaneously
      recorded, high-density EEG and BOLD-fMRI data. Using independent component
      analysis (ICA) of the combined EEG and fMRI data, we identified thirteen
      microstates and ten RSNs that are organized independently in their temporal and
      spatial characteristics, respectively. We hypothesized that the intrinsic brain
      networks that are active at rest would be reflected in both the EEG data and the
      fMRI data. To test this hypothesis, the rapid fluctuations associated with each
      microstate were correlated with the BOLD-fMRI signal associated with each RSN. We
      found that each RSN was characterized further by a specific electrophysiological
      signature involving from one to a combination of several microstates. Moreover,
      by comparing the time course of EEG microstates to that of the whole-brain BOLD
      signal, on a multi-subject group level, we unraveled for the first time a set of
      microstate-associated networks that correspond to a range of previously described
      RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor
      and default mode networks. These results extend our understanding of the
      electrophysiological signature of BOLD RSNs and demonstrate the intrinsic
      connection between the fast neuronal activity and slow hemodynamic fluctuations.

PMID- 22381594
TI  - In situ NMR of lithium ion batteries: bulk susceptibility effects and practical
      considerations.
AB  - The application of in situ nuclear magnetic resonance (NMR) to investigate
      batteries in real time (i.e., as they are cycling) provides fruitful insight into
      the electrochemical structural changes that occur in the battery. A major
      challenge for in situ static NMR spectroscopy of a battery is, however, to
      separate the resonances from the different components. Many resonances overlap
      and are broadened since spectra are acquired, to date, in static mode. Spectral
      analysis is also complicated by bulk magnetic susceptibility (BMS) effects. Here
      we describe some of the BMS effects that arise in lithium ion battery (LIB)
      materials and provide an outline of some of the practical considerations
      associated with the application of in situ NMR spectroscopy to study structural
      changes in energy materials.

PMID- 22381595
TI  - Expanded timed up and go test with subjects with stroke: reliability and
      comparisons with matched healthy controls.
AB  - OBJECTIVES: To investigate the intra- and interrater reliabilities of the
      Expanded Timed Up and Go (ETUG) test with subjects with stroke and to compare the
      ETUG scores between subjects with stroke and healthy control subjects. DESIGN:
      Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Stroke participants
      (n=48; mean age +/- SD, 59.29+/-15.84y) and healthy controls (n=48), matched by
      age, sex, and levels of physical activity. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The time spent to complete the ETUG in absolute (s) and ratio
      values regarding the percentages of the total time. Intraclass correlation
      coefficients (ICCs), Student t tests, and 95% confidence intervals were employed
      to investigate the reliability and differences between the groups (alpha<.05).
      RESULTS: Both intra- and interrater reliabilities showed significant and
      excellent results for both groups for the absolute values (0.86<=ICC<=1.00;
      P<.001) and ratio values (0.55<=ICC<=0.99; P<.001). The mean time, in seconds,
      for all of the ETUG activities was higher for the subjects with stroke than for
      the control subjects (3.15<=t<=5.78; P<.001). However, when the comparisons
      considered the ratio values, no significant differences between the groups were
      found (0.45<=t<=1.15; 0.25<=P<=0.65). These results were confirmed by the 95%
      confidence interval. CONCLUSIONS: Subjects with stroke spent more time in all of
      the ETUG activities when compared with control subjects. All of the activities
      appeared to contribute similarly to the poorer performances observed in subjects
      with stroke, because the ratio values were similar between the groups.
      Considering the positive intra- and interrater reliability results, the ETUG
      could be applied to assess the functional mobility of both groups.

PMID- 22381596
TI  - Failing to prevent birth defects caused by maternal diabetes mellitus.

PMID- 22381597
TI  - Outcomes of late preterm birth: who is at risk and for what?

PMID- 22381598
TI  - Obesity and implications for future generations.

PMID- 22381600
TI  - Childhood lead poisoning prevention through prenatal housing inspection and
      remediation in St. Louis, MO.
AB  - OBJECTIVE: We assessed the screening and remediation of home lead hazards
      prenatally in a high-risk population, hypothesizing that average blood-lead level
      and the number of poisonings would drop by 25%. STUDY DESIGN: One hundred fifty
      two women underwent prenatal home inspections by certified lead inspectors. The
      hazards that were identified were remediated. The blood-lead levels of children
      of participating women were compared with matched control subjects. RESULTS:
      Blood-lead levels were obtained from 60 children and compared with matched
      control subjects. The average blood-lead level of children in the treatment group
      was 2.70 MUg/dL vs 3.73 MUg/dL in control subjects (P = .019). The percentage of
      children with levels >10 MUg/dL in the treatment group was 0% vs 4.2% in control
      subjects (P = .128). CONCLUSION: Screening and remediation of houses of pregnant
      women is effective to reduce the average blood-lead level and number of children
      that exceed the federal level of concern for lead poisoning in a high-risk
      population.

PMID- 22381601
TI  - Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority
      open trial.
AB  - OBJECTIVE: We sought to determine whether the incidence of neonatal respiratory
      distress syndrome (RDS) is similar with 12- vs 24-hour dosing interval of
      betamethasone. STUDY DESIGN: This was a prospective, randomized, open,
      noninferiority trial. Mothers (n = 228) with a singleton or multiple pregnancies
      (fetuses = 260), between gestational age of 23-34 weeks, at risk for preterm
      delivery, received standard 2 doses of betamethasone either 12 or 24 hours apart
      in 2:1 ratio, respectively. RESULTS: Incidence of RDS was similar in the 2
      cohorts (36.5% vs 37.3%; P = not significant). Women unable to receive the
      complete course of corticosteroids with the 24-hour interval can be reduced by
      half with the 12-hour interval. However, increased incidence of necrotizing
      enterocolitis was seen with 12-hour dosing (6.2% vs 0%; P = .03). CONCLUSION: The
      12-hour dosing interval is equivalent to the 24-hour dosing interval for
      prevention of RDS in neonates of mothers delivering prematurely. A larger
      multicenter study is needed to confirm our findings.

PMID- 22381602
TI  - Intrauterine transfusion for parvovirus B19 infection: long-term
      neurodevelopmental outcome.
AB  - OBJECTIVE: To evaluate long-term neurodevelopmental outcome of children treated
      with intrauterine transfusions for fetal anemia because of parvovirus B19
      infection. STUDY DESIGN: Children treated with intrauterine transfusions for
      fetal anemia because of parvovirus B19 infection underwent standardized age
      appropriate neurodevelopmental testing. Main outcome was the incidence of
      neurodevelopmental impairment. RESULTS: Twenty-eight children were evaluated at a
      median age of 5 years (range, 1.5-13 years). Neurodevelopmental impairment was
      diagnosed in 3 of 28 (11%) children, including 1 child with combined cerebral
      palsy and severe developmental delay and 2 children with isolated severe
      developmental delay. CONCLUSION: Neurodevelopmental impairment in children
      treated with intrauterine transfusion for parvovirus B19 infection is increased
      compared with the general population. Large long-term follow-up studies are
      required to determine potential risk factors.

PMID- 22381603
TI  - Prevention of preterm delivery after successful tocolysis in preterm labor by 17
      alpha-hydroxyprogesterone caproate: a randomized controlled trial.
AB  - OBJECTIVE: The objective of the study was to evaluate the use of 17 alpha
      hydroxyprogesterone caproate (17P) to reduce preterm delivery. STUDY DESIGN: This
      open-label, multicenter, randomized controlled trial included women with
      singleton pregnancies admitted at 24-31 weeks' gestation and cervical length less
      than 25 mm for preterm labor successfully arrested by tocolytic treatment.
      Randomization assigned them to receive (or not) 500 mg of intramuscular 17P after
      tocolysis ended, repeated semiweekly until 36 weeks or preterm delivery. The
      primary outcome was the time from randomization to delivery. RESULTS: Outcome
      data were available for 184 of 188 women randomized. The 17P and control groups
      (similar for most baseline characteristics) did not differ significantly for
      median [interquartile range] time to delivery (64 [42-79] and 67 [46-83] days,
      respectively) or rates of delivery before 37, 34, or 32 weeks of gestation or
      adverse perinatal outcomes. CONCLUSION: Semiweekly injections of 17P did not
      prolong pregnancy significantly in women with tocolysis-arrested preterm labor.

PMID- 22381604
TI  - Immediate versus delayed medical treatment for first-trimester miscarriage: a
      randomized trial.
AB  - OBJECTIVE: To compare immediate vs delayed medical treatment for first-trimester
      miscarriage. STUDY DESIGN: Randomized open-label trial in a university hospital
      gynecologic emergency department. Between April 2003 and April 2006, 182 women
      diagnosed with spontaneous abortion before 14 weeks' gestation were assigned to
      immediate medical treatment (oral mifepristone, followed 48 hours later by
      vaginal misoprostol, n = 91) or sequential management (1 week of watchful waiting
      followed, if necessary, by the above-described medical treatment, n = 91). Vacuum
      aspiration was performed in case of treatment failure, hemorrhage, pain,
      infection, or patient request. RESULTS: Compared with immediate medical
      treatment, sequential management resulted in twice as many vacuum aspirations
      overall (43.5% vs 19.1%; P < .001), 4 times as many emergent vacuum aspirations
      (20% vs 4.5%; P = .001), and twice as many unplanned visits to the emergency
      department (34.1% vs 16.9%; P = .009). CONCLUSION: Delaying medical treatment of
      first-trimester miscarriage increases the rate of unplanned surgical uterine
      evacuation.

PMID- 22381605
TI  - School-age outcomes of late preterm infants in New York City.
AB  - OBJECTIVE: This study compares school-age outcomes among preterm (PT) (32 0/7-<34
      weeks), late PT (LP) (34 0/7-<37 weeks), and full-term (FT) infants to assess
      cognitive sequelae of LP births. STUDY DESIGN: We obtained linked birth and
      educational data for all nonanomalous singleton infants born 1994 through 1998 in
      New York City who had a third-grade standardized test score (n = 215,138).
      RESULTS: Children delivered LP and PT had 30% and 50% higher adjusted odds of
      needing special education than those delivered FT (adjusted odds ratio, 1.34; 95%
      confidence interval, 1.29-1.40; and adjusted odds ratio, 1.53; 95% confidence
      interval, 1.30-1.69). They also had lower adjusted math and English scores than
      those delivered FT (math: 7% and 10% of SD, respectively; English: 4% and 6% of
      SD). A linear association between gestational age and test scores was seen
      through 39 weeks' gestation. CONCLUSION: There is a significant risk of
      developmental differences in PT and LP infants compared with FT infants.

PMID- 22381606
TI  - Obstetric decision-making and counseling at the limits of viability.
AB  - OBJECTIVE: The purpose of this study was to examine factors that influence
      obstetric decision-making and counseling for periviable deliveries and to
      describe counseling challenges. STUDY DESIGN: Twenty-one semistructured
      interviews were conducted with obstetricians who were recruited from 5 academic
      medical centers in Philadelphia. Two trained reviewers independently coded
      transcripts using grounded theory methods. Research software facilitated
      qualitative analysis. RESULTS: Circumscribed by institutional norms and clinical
      acuity, obstetric decision-making and counseling were influenced primarily by
      patient preferences. Perspectives on patient autonomy guided approaches to
      counseling. Thresholds for intervention varied from "attending to attending" and
      "institution to institution." Sociodemographic factors were not believed to
      influence clinical decision-making. However, obstetricians admittedly managed in
      vitro fertilization pregnancies more aggressively. Communicating uncertainty,
      managing expectations, assessing understanding, and relaying consistent messages
      across specialties were frequently described counseling challenges for
      obstetricians. CONCLUSION: The impact of institutional variation and in vitro
      fertilization on periviable decision-making warrants further consideration.
      Interventions to train and support obstetricians in communicating uncertainty,
      managing expectations, and assessing values and understanding are needed.

PMID- 22381607
TI  - Did drug therapy contribute?: severe pelvic organ prolapse followed initiation of
      high-dose glucocorticoid treatment.

PMID- 22381608
TI  - Discussion: 'Surgical staging in early ovarian carcinoma' by Garcia-Soto et al.
AB  - In the roundtable that follows, clinicians discuss a study published in this
      issue of the Journal in light of its methodology, relevance to practice, and
      implications for future research.

PMID- 22381609
TI  - Ischiorectal fossa abscess after pelvic floor injection of botulinum toxin.
AB  - Botulinum toxin is used to treat pelvic floor tension myalgia; however, its
      safety profile is poorly understood. We report an ischiorectal fossa abscess
      after pelvic floor injections of botulinum toxin. Physicians need to be aware of
      this possible complication, consider alternate injection techniques and
      antiseptic preparation before injection.

PMID- 22381610
TI  - Fatal right heart failure complicating undiagnosed metastatic breast cancer.

PMID- 22381611
TI  - Fournier's gangrene and its characteristic ultrasound findings.

PMID- 22381612
TI  - Torsion of a wandering spleen treated with partial splenectomy and splenopexy.
AB  - BACKGROUND: Wandering spleen is a rare and unusual entity, characterized by
      excessive mobility and displacement of the organ from its normal position. This
      happens due to congenital or acquired anomalies leading to the lack of the
      spleen's suspensory ligaments. Clinical presentation is variable; acute abdominal
      pain may occur when persistent torsion of the splenic pedicle results in splenic
      infarction. Ultrasonography, computed tomography, and magnetic resonance imaging
      are modalities that may be used in diagnosis. The treatment of choice is surgery,
      with splenectomy or splenopexy, the latter being preferred. CASE REPORT: The
      patient was a 38-year-old woman with a 10-day history of left-sided abdominal
      pain. Imaging demonstrated a wandering spleen with partial infarction of the
      inferior pole. An open partial splenectomy with splenopexy of the remaining
      spleen was performed with the use of an absorbable mesh sutured to the abdominal
      wall and stomach. Her recovery was uneventful and on follow-up she had no signs
      of recurrence or complications. CONCLUSION: Wandering spleen should be considered
      in cases of acute abdominal pain, and surgery is the treatment of choice, with
      the goal of preservation of the organ whenever possible.

PMID- 22381613
TI  - Effects of two in-office bleaching agents with different pH values on enamel
      surface structure and color: an in situ vs. in vitro study.
AB  - OBJECTIVES: To investigate in situ and in vitro effects of acidic and neutral in
      office bleaching agents on human enamel in terms of chemical structure and tooth
      color. METHODS: Ninety enamel slabs were obtained from premolars. Then specimens
      were randomly distributed into six groups (n=15) and the human saliva (HS) in
      volunteers' oral cavities was used to simulate in situ condition: group
      Beyond+distilled water (DW); group Opalescence Boost (O-Boost)+DW; group
      control+DW; group Beyond+HS; group O-Boost+HS and group control+HS. Twice in
      office bleaching treatments were performed with a one-week interval and the total
      bleaching time was 90 min. ATR-IR spectroscopy, Raman spectroscopy and color
      measurement were performed before the bleaching treatment and after one week post
      treatment, respectively. Then ATR-IR and Raman spectroscopies were analysed and
      the carbonate: mineral (C:M) ratio, Raman absolute intensity (RAI), Raman
      relative intensity (RRI) and laser-induced fluorescence intensity (FI) were
      calculated for evaluation. RESULTS: C:M ratio and percentage RRI showed
      significantly decrease in group Beyond+DW (p<0.001, p<0.001) while little
      variation was observed in the other groups (p>0.05, p>0.05). Percentage FI and
      DeltaE revealed statistical difference in all bleached groups (p<0.001, p<0.001)
      while no statistical difference in control groups (p>0.05, p>0.05). CONCLUSION:
      Acidic and neutral in-office bleaching agents had the same whitening efficiency
      in situ and in vitro. Acidic agents could induce demineralisation of human enamel
      in vitro and the presence of natural human saliva could minimise this adverse
      effect.

PMID- 22381614
TI  - Bonding effectiveness of a new 'multi-mode' adhesive to enamel and dentine.
AB  - OBJECTIVES: Self-etch adhesives are well adopted in general practice, obviously
      primarily thanks to their ease of use and fast application time. Nevertheless,
      phosphoric acid is still often recommended to beforehand etch enamel following a
      so-called 'selective' enamel-etch technique, this in particular when most cavity
      margins end in enamel. The purpose of this study was to test if a new one-step
      adhesive can be applied in a multi-mode manner, this following different, either
      'full' or 'selective', self-etch and etch-and-rinse approaches. Specific research
      hypotheses tested were that prior phosphoric-acid etching did not affect the
      bonding effectiveness of the one-step adhesive to enamel and dentine, and that
      the bonding effectiveness to dentine was also not affected when the adhesive was
      applied either following a 'dry-bonding' or 'wet-bonding' etch-and-rinse
      technique. METHODS: The micro-tensile bond strength (MUTBS) of the one-step self
      etch adhesive G-Bond Plus (GC, Tokyo, Japan; 1-SEA) was measured when it was
      bonded to bur-cut enamel following either a 'self-etch' or an 'etch-and-rinse'
      adhesive protocol, and to bur-cut dentine when applied following either a 'self
      etch', a 'dry-bonding' or a 'wet-bonding' etch-and-rinse adhesive protocol. Bond
      strength testing was corroborated by ultra-structural analysis of the interfacial
      interaction at enamel and dentine using transmission electron microscopy (TEM).
      RESULTS: Prior phosphoric-acid etching significantly increased the bonding
      effectiveness of the 1-SEA to enamel. A clearly enhanced micro-retentive surface
      was revealed by TEM. To dentine, no statistically significant difference in
      bonding effectiveness was recorded when the 1-SEA was either applied following a
      self-etch or both etch-and-rinse approaches. The 'dry-bonding' etch-and-rinse
      protocol was significantly more effective than its 'wet-bonding' version. TEM
      however revealed indications of low-quality hybridisation following both etch-and
      rinse approaches, in particular in the form of a porous and poorly resin
      infiltrated collagen mesh. CONCLUSIONS: While phosphoric-acid etching definitely
      improved bonding of the one-step self-etch adhesive to enamel, one should be more
      careful with additional phosphoric-acid etching of dentine. Although the bond
      strength was not reduced, the resultant adhesive interface appeared ultra
      structurally more vulnerable to biodegradation.

PMID- 22381615
TI  - Structural changes in freshwater fish and chironomids exposed to bacterial
      exotoxins.
AB  - Mass fish mortalities have been reported in the past decade from British waters,
      often coinciding with blooms of filamentous actinobacteria, particularly strains
      of Streptomyces griseus. The present study has shown that some fractions of the
      exudate of S. griseus, prepared after a series of high pressure liquid
      chromatography (HPLC) separations, and analysed with liquid chromatography mass
      spectrometry (LC-MS), induced pathological changes to the gills of carp and/or
      tench fry following exposure under laboratory conditions up to 96 h Similar
      changes were induced by streptomycin, a secondary metabolite of S. griseus, and
      these included loss of microridging and fusion of secondary lamellae, with carp
      fry in the case of the exudate of S. griseus being more sensitive than tench fry,
      especially with exposure to fraction 9 and selected sub-fractions of 9. Some
      deformities using a severity index were also observed in the head capsule of
      larvae of the non-biting midge Chironomus riparius, including loss and splitting
      of teeth on the mentum. The results are discussed in relation to further
      identification of metabolites derived from samples of the organic filtrate of S.
      griseus and implications for the functioning of freshwater ecosystems.

PMID- 22381616
TI  - A multibiomarker approach in juvenile turbot, Scophthalmus maximus, exposed to
      contaminated sediments.
AB  - Juvenile turbot were exposed in laboratory conditions to a mixture of chemical
      contaminants associated with harbour and estuarine sediments for seven and 21
      days. Several molecular biomarkers of exposure were then measured in fish liver:
      two biotransformation parameters [ethoxyresorufin-O-deethylase (EROD) and phase
      II glutathione S-transferase (GST) activities] and an antioxidant enzyme activity
      [catalase (CAT)]. Modifications at the histological level were analysed by the
      measurement of the number and size of melanomacrophage centres (MMCs) and
      disturbances to the immune function by the measurement of cytokine transforming
      growth factor-beta (TGF-beta) and development of the thymus. The responses of
      these molecular and immunological biomarkers were correlated with metal and PAH
      concentrations measured in sediments and with the physiological performance of
      turbot analysed in a previous study on the same fish (growth rates, condition
      factor K, RNA:DNA ratio and lipid index). While no difference was found in thymus
      analysis, some molecular and immunological responses were observed in fish
      exposed to contaminated sediments. Weak relationships between molecular
      biomarkers' responses and PAH concentrations were recorded, while their responses
      were significantly correlated with some metals. MMC and aggregates were weakly
      related to chemical contaminants whereas some significant correlations were found
      between TGF-b1 responses and some metal concentrations. However, molecular and
      immunological biomarkers were weakly related to fish physiological damages since
      low responses were observed in the condition which led to the lowest growth and
      condition indices. These data suggest the complexity of cause-effect
      relationships between exposure to pollutants, metabolisms and health damages.
      Precautions should be considered in the use of molecular and immunological
      biomarkers alone in biomonitoring programs. Their complementary use with
      physiological biomarkers, such as fish growth and condition indices, could
      improve their utilisation.

PMID- 22381617
TI  - Acute toxicity of butachlor and atrazine to freshwater green alga Scenedesmus
      obliquus and cladoceran Daphnia carinata.
AB  - Both single and joint toxicity of atrazine and butachlor to freshwater green alga
      Scenedesmus obliquus and cladoceran Daphnia carinata isolated from South China
      were investigated in the present study. The 96 h-EC(50) values of atrazine and
      butachlor to S. obliquus were 0.0147 and 2.31 mg L(-1), while the 48 h-LC(50)
      values to D. carinata were 60.6 and 3.40 mg L(-1), respectively. These results
      suggest that atrazine could be highly toxic to S. obliquus and slightly toxic to
      D. carinata, while butachlor exhibits moderate toxicity to both organisms. The
      additive indexes of atrazine and butachlor mixtures were -2.68 (-3.02 to -2.32)
      to S. obliquus and 0.054 (-0.025 to 0.238) to D. carinata, respectively.
      Therefore, the joint action of two herbicides was significant antagonism to S.
      obliquus, while significant synergism was not shown to D. carinata. Moreover,
      significant linear correlation between the natural logarithm of herbicide
      concentrations and growth rates of alga S. obliquus was observed. Taken together,
      it is the first study reporting the toxicity endpoints for mixture of atrazine
      and butachlor against S. obliquus and D. carinata isolated from south China. The
      present results would be helpful to provide data to assess the ecological risk of
      both herbicides to aquatic organisms.

PMID- 22381619
TI  - Can tired bullets cause serious injuries? A case report and review of the
      literature.

PMID- 22381620
TI  - Meiotic non-disjunction mechanisms in human fertile males.
AB  - BACKGROUND: In humans, little is known about the mechanisms of non-disjunction
      working in male meiosis, although considerable attention has been given to these
      mechanisms in female meiosis. The present study explores the origin of meiotic
      non-disjunction during human spermatogenesis and the chromosomes most commonly
      involved in this process. METHODS: We used Multiplex fluorescence in situ
      hybridization to carry out meiotic analyses in metaphase I (MI) and metaphase II
      (MII) spermatocytes from three fertile donors. Testicular biopsy was obtained
      during a vasectomy procedure. RESULTS: We examined a total of 317 MI and 248 MII
      spermatocytes. The frequency of numerical chromosome abnormalities at MII (14.5%)
      was 5.5 times higher than at MI (2.5%). We observed 88 (27.7%) spermatocytes I
      with chromosome bivalents with a low chiasma count, usually small chromosomes
      displaying two separated univalents. Chromosomes X, Y and 21 were the most
      commonly found as achiasmate chromosomes at MI and the most frequently involved
      in disomy at MII. Hyperploidy frequency in spermatocytes II (disomy) was
      significantly higher (P< 0.001) than that found in spermatocytes I (trisomy).
      CONCLUSIONS: Achiasmate non-disjunction and premature separation of sister
      chromatids appear to be the two main non-disjunction mechanisms during the first
      meiotic division in human spermatogenesis, and both mechanisms contribute equally
      to the genesis of aneuploidy. The elevated frequencies of disomy detected in
      spermatocytes II are significantly higher than those previously described in
      human spermatozoa, suggesting the existence of a postmeiotic checkpoint
      monitoring numerical abnormalities.

PMID- 22381618
TI  - Regulation of the human catalytic subunit of telomerase (hTERT).
AB  - Over the past decade, there has been much interest in the regulation of
      telomerase, the enzyme responsible for maintaining the integrity of chromosomal
      ends, and its crucial role in cellular immortalization, tumorigenesis, and the
      progression of cancer. Telomerase activity is characterized by the expression of
      the telomerase reverse transcriptase (TERT) gene, suggesting that TERT serves as
      the major limiting agent for telomerase activity. Recent discoveries have led to
      characterization of various interactants that aid in the regulation of human TERT
      (hTERT), including numerous transcription factors; further supporting the pivotal
      role that transcription plays in both the expression and repression of
      telomerase. Several studies have suggested that epigenetic modulation of the
      hTERT core promoter region may provide an additional level of regulation.
      Although these studies have provided essential information on the regulation of
      hTERT, there has been ambiguity of the role of methylation within the core
      promoter region and the subsequent binding of various activating and repressive
      agents. As a result, we found it necessary to consolidate and summarize these
      recent developments and elucidate these discrepancies. In this review, we focus
      on the co-regulation of hTERT via transcriptional regulation, the presence or
      absence of various activators and repressors, as well as the epigenetic pathways
      of DNA methylation and histone modifications.

PMID- 22381622
TI  - YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in
      alveolar macrophages.
AB  - Alveolar macrophages play significant roles in the pathogenesis of several
      inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well
      documented to reflect disease severity in the airway. In this study, we
      investigated the effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC
      1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E1 (a
      stable PGE2 analogue) and forskolin (a adenylate cyclase activator) induced NO
      production and inducible NO synthase (iNOS) expression in rat alveolar
      macrophages (NR8383). YC-1 did not directly cause NO production or iNOS
      expression, but drastically potentiated PGE1- or forskolin-induced NO production
      and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC
      1 and PGE1 significantly increased phosphorylation of the cAMP response element
      binding protein (CREB), but not nuclear factor (NF)-kappaB activation. The
      combined effect on NO production, iNOS expression, and CREB phosphorylation was
      reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the
      potentiating functions were mediated through a cAMP/PKA signaling pathway.
      Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO
      release, iNOS expression, and CREB activation. YC-1 treatment induced an increase
      in PGE1-induced cAMP formation, which occurred through the inhibition of cAMP
      specific phosphodiesterase (PDE) activity. Furthermore, the combination of
      rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and
      PGE1 also triggered NO production and iNOS expression. In summary, YC-1
      potentiates PGE1-induced NO production and iNOS expression in alveolar
      macrophages through inhibition of cAMP PDE activity and activation of the
      cAMP/PKA/CREB signaling pathway.

PMID- 22381621
TI  - DNA methylation changes in whole blood is associated with exposure to the
      environmental contaminants, mercury, lead, cadmium and bisphenol A, in women
      undergoing ovarian stimulation for IVF.
AB  - BACKGROUND: Changes in DNA methylation may play an important role in the
      deleterious reproductive effects reported in association with exposure to
      environmental pollutants. In this pilot study, we identify candidate methylation
      changes associated with exposure to pollutants in women undergoing in vitro
      fertilization (IVF). METHODS: Blood and urine were collected from women on the
      day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine
      for cadmium using inductively coupled plasma mass spectrometry. Unconjugated
      bisphenol A (BPA) was analyzed in serum using high-performance liquid
      chromatography with Coularray detection. Participants were dichotomized as higher
      or lower exposure groups by median concentrations. Using the Illumina GoldenGate
      Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was
      assessed at 1505 CpG sites for association with exposure levels of each
      pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05)
      and an absolute difference >10% which were confirmed using bisulfite
      pyrosequencing. RESULTS: Methylation of the GSTM1/5 promoter was increased for
      women with higher mercury exposure (P= 0.04); however, no correlation was
      observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2
      promoter in women with higher exposure to lead (P= 0.004), and an inverse
      correlation was observed (r = - 0.45, P= 0.03). Lower methylation of a promoter
      CpG site at the TSP50 gene was detected in women with higher BPA exposure (P=
      0.005), and again an inverse correlation was identified (r = - 0.51, P= 0.001).
      CONCLUSIONS: Altered DNA methylation at various CpG sites was associated with
      exposure to mercury, lead or BPA, providing candidates to be investigated using a
      larger study sample, as the results may reflect an independently associated
      predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell
      composition). Further studies accommodating variations in these factors will be
      needed to confirm these associations and identify their underlying causes.

PMID- 22381623
TI  - Identification of contact and respiratory sensitizers according to IL-4 receptor
      alpha expression and IL-2 production.
AB  - Identification of allergenic chemicals is an important occupational safety issue.
      While several methods exist to identify contact sensitizers, there is currently
      no validated model to predict the potential of chemicals to act as respiratory
      sensitizers. Previously, we reported that cytometry analysis of the local immune
      responses induced in mice dermally exposed to the respiratory sensitizer
      trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB
      1%) could identify divergent expression of several immune parameters. The present
      study confirms, first, that IgE-positive B cells, MHC class II molecules,
      interleukin (IL)-2, IL-4 and IL-4Ralpha can differentiate the allergic reactions
      caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene
      diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone).
      The second part of the study was designed to test the robustness of these markers
      when classing the weakly immunogenic chemicals most often encountered. Six
      respiratory allergens, including TMA (2.5%), five contact allergens, including
      DNCB (0.25%), and two irritants were compared at doses of equivalent
      immunogenicity. The results indicated that IL-4Ralpha and IL-2 can be reliably
      used to discriminate sensitizers. Respiratory sensitizers induced markedly higher
      IL-4Ralpha levels than contact allergens, while irritants had no effect on this
      parameter. Inversely, contact allergens tended to induce higher percentages of IL
      2+CD8+ cells than respiratory allergens. In contrast, the markers MHC-II, IgE and
      IL-4 were not able to classify chemicals with low immunogenic potential. In
      conclusion, IL-4Ralpha and IL-2 have the potential to be used in classifying a
      variety of chemical allergens.

PMID- 22381625
TI  - Low frequency mechanical stimulation inhibits adipogenic differentiation of
      C3H10T1/2 mesenchymal stem cells.
AB  - Oscillatory mechanical stimulation at relatively high frequencies (0.1 Hz) has
      been shown to inhibit adipogenic and promote osteogenic differentiation of
      mesenchymal stem cells. However, for physiological interpretations and ease of
      implementation it is of interest to know whether different rates of mechanical
      stimulation can produce similar results. We hypothesized that relatively low
      frequency mechanical stimulation (0.01 Hz) can inhibit adipogenic differentiation
      of C3H10T1/2 mouse mesenchymal stem cells, even in a potent adipogenic
      differentiation medium. C3H10T1/2 cells were cultured in adipogenic medium under
      control (non-mechanically stimulated) conditions and under oscillatory surface
      stretch with 10% amplitude and 0.01 Hz frequency for 6h per day for up to 5 days.
      Cell population was assessed by counting and adipogenic differentiation was
      assessed by real-time quantitative PCR (qPCR) analysis of peroxisome proliferator
      activated receptor gamma (PPARgamma) and fatty acid binding protein 4 (FABP4)
      after 3 and 5 days. Involvement of the ERK signaling pathway was assessed by
      Western blot. Low frequency mechanical stimulation significantly decreased
      expression of PPARgamma after 3 days and FABP4 after 3 and 5 days versus non
      stimulated culture. ERK signaling was decreased in mechanically-stimulated
      culture, indicating a role in the inhibition of adipogenic differentiation.
      Application of this study: Low frequency mechanical stimulation may provide a
      technically simple means for control of mesenchymal stem cell differentiation in
      cell-based therapies, particularly for inhibition of differentiation toward
      undesired adipogenic lineages.

PMID- 22381624
TI  - Developmental effects of tobacco smoke exposure during human embryonic stem cell
      differentiation are mediated through the transforming growth factor-beta
      superfamily member, Nodal.
AB  - While the pathologies associated with in utero smoke exposure are well
      established, their underlying molecular mechanisms are incompletely understood.
      We differentiated human embryonic stem cells in the presence of physiological
      concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis,
      quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has
      lineage- and stage-specific effects on human embryonic stem cell differentiation,
      through both nicotine-dependent and -independent pathways. We show that three
      major stem cell pluripotency/differentiation pathways, Notch, canonical Wnt, and
      transforming growth factor-beta, are affected by smoke exposure, and that Nodal
      signaling through SMAD2 is specifically impacted by effects on Lefty1, Nodal, and
      FoxH1. These events are associated with upregulation of microRNA-302a, a post
      transcriptional silencer of Lefty1. The described studies provide insight into
      the mechanisms by which tobacco smoke influences fetal development at the
      cellular level, and identify specific transcriptional, post-transcriptional, and
      signaling pathways by which this likely occurs.

PMID- 22381626
TI  - Colchicine affects cell motility, pattern formation and stalk cell
      differentiation in Dictyostelium by altering calcium signaling.
AB  - Previous work, verified here, showed that colchicine affects Dictyostelium
      pattern formation, disrupts morphogenesis, inhibits spore differentiation and
      induces terminal stalk cell differentiation. Here we show that colchicine
      specifically induces ecmB expression and enhances accumulation of ecmB-expressing
      cells at the posterior end of multicellular structures. Colchicine did not induce
      a nuclear translocation of DimB, a DIF-1 responsive transcription factor in
      vitro. It also induced terminal stalk cell differentiation in a mutant strain
      that does not produce DIF-1 (dmtA-) and after the treatment of cells with DIF-1
      synthesis inhibitor cerulenin (100 MUM). This suggests that colchicine induces
      the differentiation of ecmB-expressing cells independent of DIF-1 production and
      likely through a signaling pathway that is distinct from the one that is utilized
      by DIF-1. Depending on concentration, colchicine enhanced random cell motility,
      but not chemotaxis, by 3-5 fold (10-50 mM colchicine, respectively) through a
      Ca(2+)-mediated signaling pathway involving phospholipase C, calmodulin and
      heterotrimeric G proteins. Colchicine's effects were not due to microtubule
      depolymerization as other microtubule-depolymerizing agents did not have these
      effects. Finally normal morphogenesis and stalk and spore cell differentiation of
      cells treated with 10 mM colchicine were rescued through chelation of Ca2+ by
      BAPTA-AM and EDTA and calmodulin antagonism by W-7 but not PLC inhibition by U
      73122. Morphogenesis or spore cell differentiation of cells treated with 50 mM
      colchicine could not be rescued by the above treatments but terminal stalk cell
      differentiation was inhibited by BAPTA-AM, EDTA and W-7, but not U-73122. Thus
      colchicine disrupts morphogenesis and induces stalk cell differentiation through
      a Ca(2+)-mediated signaling pathway involving specific changes in gene expression
      and cell motility.

PMID- 22381627
TI  - Deltamethrin and permethrin residue on long-lasting insecticidal nets after 18
      months of use in a visceral leishmaniasis-endemic area in Nepal.
AB  - The insecticide residue on two types of long-lasting insecticidal nets (LLIN),
      Olyset Net and PermaNet 2.0, used in a visceral leishmaniasis-endemic village in
      eastern Nepal was quantified using HPLC. After two washes during 18 months of use
      the mean insecticide residues on PermaNet 2.0 and Olyset Net were 53.5 mg/m(2)
      (97.3% of the target dose) of deltamethrin and 911.8 mg/m(2) (91.2% of the target
      dose) of permethrin, respectively. These residues were close to the insecticide
      loads specified by the manufacturers of the two LLINs. The use of LLINs has been
      postulated as an alternative or complementary method to indoor residual spraying.
      Our results suggest that LLINs should be washed 4-5 times each year throughout
      their lifespan by specifically requesting villagers to wash nets on certain
      dates. The insecticide residue on the nets and their bioefficacy against sand fly
      vectors should be monitored after each wash, in various cultural settings, to
      assess their durability and long-term retention of the insectide.

PMID- 22381628
TI  - DNA extraction from dried Schistosoma haematobium eggs isolated on nylon filters.
AB  - Genetic studies on Schistosoma haematobium are often carried out on DNA extracted
      from miracidia, cercariae or adult worms. This paper presents a method for
      extracting DNA from S. haematobium eggs collected from urine samples and stored
      on nylon filters at room temperature. DNA was extracted from dried S. haematobium
      eggs using the DNeasy Blood & Tissue Kit (QIAGEN Sample & Assay Technologies,
      Copenhagen, Denmark). Selected genes were amplified using PCR to verify that DNA
      extraction had been successful. DNA was extracted from 45 samples and 31 had a
      positive PCR reaction for either or both of the two selected genes.

PMID- 22381629
TI  - Meniscal scaffolds: early experience and review of the literature.
AB  - INTRODUCTION: Meniscal scaffold implants support the in-growth of new "meniscus
      like" tissue with the aim of alleviating post-meniscectomy knee pain and
      preventing further articular cartilage degeneration. PATIENTS AND METHODS: Twenty
      three patients underwent meniscal scaffold implantation (14 medial, 9 lateral)
      with either the Menaflex (ReGen Biologics) (n=12) or Actifit (Orteq) (n=11)
      scaffolds. Minimum follow-up was 1 year with a mean of 24.1 months (18-27) for
      the Menaflex and 14.7 months (12-18) for the Actifit groups. Mean age at surgery
      was 35 years (17-47) with a mean Outerbridge grade of 1.9 in the affected
      compartment. Eight (36%) underwent concurrent osteotomy, ligament reconstruction
      or microfracture of the tibial plateau. KOOS, Lysholm, Tegner activity and IKDC
      scores were collected pre-operatively and at six-month interval post-surgery.
      Assessment of the reconstruction was obtained with MRI scanning and arthroscopy.
      One scaffold tore and was revised at 19 months post-operatively. RESULTS: Twenty
      one out of 23 (91.3%) had a significant improvement in knee scores when compared
      to pre-surgery levels at latest follow-up. Second-look arthroscopy in 14 at 1
      year post-implantation showed variable amounts of regenerative tissue. There was
      no progression in chondral wear noted on repeat MRI scanning. CONCLUSION:
      Treatment with meniscal scaffold implants can provide good pain relief for the
      post-meniscectomy knee following partial meniscectomy. Longer follow-up is
      required to ascertain whether they also prevent the progressive chondral wear
      associated with a post-meniscectomy knee.

PMID- 22381638
TI  - Is it time to rethink the typical course of low back pain?
AB  - OBJECTIVE: To determine the frequency and the characteristics of low back pain
      (LBP) recurrences. The research questions were as follows: (1) Are LBP
      recurrences common? (2) Do episodes worsen with multiple recurrences? (3) Does
      pain change location in any recognizable pattern during an episode? DESIGN:
      Single-page self-administered questionnaire. SETTING: Thirty clinical practices
      (primary care, physical therapy, chiropractic, and surgical spine) in North
      America and Europe. PATIENTS: A convenience sample of 589 respondents with LBP.
      There were no exclusions based on type of LBP, history of onset, or
      comorbidities. METHODS: The survey was distributed during patients' assessment or
      initial treatment at their respective clinics. The survey queried the following:
      (1) the severity of original versus most recent episodes based on the following:
      pain intensity, interference with leisure and work activities, duration of
      episodes, and most distal extent of pain; and (2) changes in pain location within
      episodes. RESULTS: In response to research question 1, a previous episode was
      reported by 73%; of those, 66.1% reported their first episode lasted <=3 months,
      54% reported >=10 episodes, and 19.4% reported >50 episodes. In response to
      research question 2, of those with recurrences, 61.1% reported that at least one
      of the survey domains was worse in recent episodes (P < .01) and only 36.9%
      reported that they were better; 20.5% were worse in all domains, whereas 8.6%
      were better or the same. In response to research question 3, the pain location
      changed during the episode in 75.6%; of these, 63.2% reported that their pain
      first spread distally before retreating proximally during recovery; there was a
      strong trend toward those reporting worsening episodes also reporting proximal-to
      distal-to-proximal changes in pain location during their episodes (r = 0.132, P <
      .06). CONCLUSION: Recurrent LBP episodes were common and numerous. Recurrences
      often worsened over time. It seems inappropriate to characterize the typical
      course of LBP as benign and favorable.

PMID- 22381639
TI  - Molecular evolution and phylogenetic analysis of genes related to cotton fibers
      development from wild and domesticated cotton species in Gossypium.
AB  - The domestication of both diploid and tetraploid cotton species was carried out
      for fiber utilization. To understand the origin and domestication of fibers, 18
      genes related to fiber development were individually cloned and sequenced from 22
      different cotton species. Their structures, phylogenetic relationship and
      molecular evolution were further studied. In the orthologous and homeologous loci
      of the 18 genes, the sequence and structure of 72.22% were conserved and 27.78%
      were diverse. Tree topologies constructed based on the combined sequences showed
      that all 13 D-genome species were congruent with Fryxell's subsection taxonomy,
      the A- and D-subgenomes independently evolved in the allopolyploid after
      polyploid formation, and Gossypium raimondii had the closest relationship with
      all allotetraploids of D-subgenomes. The molecular evolutionary rates revealed
      approximately equivalent rates among different D-genome species, and purifying
      selection acted on all genes in the wild D-genome species. Among orthologs and
      homeologs, the D-subgenomes had higher evolutionary rates than the A-subgenomes
      in tetraploid cotton species, and the cultivars had higher evolutionary rates
      than either the semi-domesticated or wild species. Our study revealed that human
      domestication altered the molecular evolutionary pattern of genes related to
      fiber development, and Gossypium hirsutum endured greater selective pressures
      than Gossypium barbadense during the domestication process.

PMID- 22381640
TI  - Predicting adolescents' persistence, non-persistence, and recent onset of
      nonmedical use of opioids and stimulants.
AB  - This study sought to distinguish among adolescents who were persistent, non
      persistent, or recent onset nonmedical users of prescription opioids and
      stimulants (respondents' ages ranged from 12-17 years, N=126,764). The
      multinomial logistic regression analyses of combined data from the 2003 through
      2009 National Survey of Drug Use and Health were used to investigate the
      association of respondents' sex, age, family income, race, parental status,
      population density, and user status (persistent, non-persistent, recent onset) on
      common illicit substances (cigarettes, alcohol, marijuana, and inhalants) with
      opioid and stimulant use. The odds of nonmedical opioid and stimulant use were
      significantly greater for females than males, and increased with age. Results
      were mixed for income, race, and parental status. Population density was largely
      unrelated to nonmedical use. Persistent nonmedical users of common illicit
      substances, especially marijuana and inhalants, were at greatest risk for
      nonmedical opioid and stimulant use. Non-persistent use of common illicit
      substances was a strong predictor of both non-persistent opioid and stimulant
      use. Recent onset of common substance use predicted recent onset of prescription
      opioid and stimulant use. Results indicate that persistence may be related to
      polysubstance use involving prescription opioids and stimulants, supporting
      efforts to investigate the underlying causes of polysubstance use.

PMID- 22381641
TI  - Head and neck basal cell carcinoma prevalence in individuals submitted to
      childhood X-ray epilation for tinea capitis treatment.
AB  - BACKGROUND: A higher prevalence for basal cell carcinoma (BCC) has been
      associated with radiation, namely with tinea capitis epilation treatment.
      OBJECTIVE: To evaluate the prevalence of head and neck basal cell carcinoma (BCC)
      and to identify the major risk factors for BCC in individuals irradiated in
      childhood for tinea capitis treatment. METHODS: We clinically observed 1,308
      individuals from an original cohort of 5,356 irradiated between 1950 and 1963,
      registering previous skin lesions excisions and proposing for surgery all the
      suspicious lesions detected. In 585 participants, 47 with BCC, the skin
      pigmentation was measured. RESULTS: The overall prevalence of BCC was 8.0% and of
      multiple BCC was 2.4%. Both total (14.7%) and multiple BCC (6.6%) were
      significantly more common in the individuals who had received a higher radiation
      dose. Multiple BCC was more prevalent (3.7%) in younger irradiated individuals
      and total BCC (9.4%) in women. Participants with BCC and without BCC presented
      similar skin pigmentation. CONCLUSION: Younger age at irradiation, higher dose
      and female gender increased the risk of developing BCC in these irradiated
      individuals.

PMID- 22381642
TI  - Lipidomics: when apocrypha becomes canonical.
AB  - Lipidomics is a branch of the field of metabolomics. Although only about a decade
      since its inception, lipidomics has already had a major influence on the way in
      which questions about lipid metabolism and signaling are posed. The field is
      intertwined in the culture and rich history of mass spectrometry. Early work
      emphasized analytical issues such as limits of detection and numbers of molecular
      species quantitated in single injections. Increased sophistication in
      applications of lipidomic analysis and emerging technologies, such as imaging
      mass spectrometry, are facilitating the study of lipid metabolism and signaling
      species in cellular functions and human diseases. In the coming years we
      anticipate a richer understanding of how specific lipid species mediate complex
      biological processes and interconnections between cellular pathways that were
      thought to be disparate.

PMID- 22381643
TI  - Dietary amino acids and blood pressure: a cohort study of patients with
      cardiovascular disease.
AB  - BACKGROUND: Dietary protein has been variably reported to either lower or raise
      blood pressure. The purpose of this study was to determine whether intakes of
      specific amino acids differentially associate with blood pressure. STUDY DESIGN:
      Observational cohort study by secondary analysis of clinical trial data. SETTING
      & PARTICIPANTS: Study of low-fat versus Mediterranean-style diets in patients
      with prevalent cardiovascular disease. PREDICTOR: Dietary amino acids. OUTCOMES:
      Systolic and diastolic blood pressure. MEASUREMENTS: Dietary nutrients and
      cardiovascular risk factors were assessed at baseline, 3 and 6 months, and then
      every 6 months for 2 years. RESULTS: Baseline blood pressure was 119 +/- 16
      (SD)/72 +/- 10 (SD) mm Hg (n = 92) and dietary protein intake was 80 +/- 31 g/d.
      Independent amino acid variables (quartiles of intake) were analyzed by
      generalized estimating equation models with prespecified covariates for time
      varying systolic and diastolic blood pressure. The odds of each 1-SD higher
      systolic or diastolic blood pressure (ie, 16 and 10 mm Hg, respectively) were
      increased per quartile of intake for methionine (ORs of 1.29 [95% CI, 1.14-1.46]
      and 1.21 [95% CI, 1.05-1.39], respectively) and alanine (ORs of 1.17 [95% CI,
      1.05-1.30] and 1.22 [95% CI, 1.07-1.38], respectively). Quartiles of intake for
      threonine (ORs of 0.84 [95% CI, 0.74-0.96] and 0.87 [95% CI, 0.75-1.01],
      respectively) and histidine (ORs of 0.92 [95% CI, 0.86-1.00] and 0.89 [95% CI,
      0.82-0.97], respectively) had inverse associations with the same degree of
      difference in blood pressure. LIMITATIONS: Modest sample-size biases toward the
      chance of false-negative results; potential for residual confounding; colinearity
      between amino acids may obscure relevant relationships to blood pressure;
      associational findings do not establish causality. CONCLUSIONS: Intakes of
      methionine and alanine were associated positively with higher blood pressure,
      whereas intakes of threonine and histidine had inverse associations. These amino
      acids merit further study for advancing dietary approaches to blood pressure
      reduction.

PMID- 22381644
TI  - Come on little lady.

PMID- 22381645
TI  - Source monitoring in children with and without fetal alcohol spectrum disorders.
AB  - OBJECTIVES: Deficits in memory are well-documented in children with fetal alcohol
      spectrum disorders (FASD); however, one aspect of memory not yet studied in
      children with FASD is source monitoring. This study examined overall source
      monitoring ability and performance profiles of children with FASD compared to
      controls. METHOD: Participants included 19 children with FASD and 38 typically
      developing children (aged 6-12 years). Children were presented with auditory word
      lists and were required to recall the source of words for reality, external, and
      internal source monitoring tasks. RESULTS: Children with FASD showed poorer
      performance than controls across all three conditions in both recognition memory
      and memory for source. However, both groups exhibited a comparable pattern of
      performance across conditions. Specifically, performance was lowest on the
      internal task and highest on the reality task. CONCLUSIONS: Information about
      source monitoring deficits further delineates the intricacies of memory deficits
      in FASD, and has implications for both assessment and intervention.

PMID- 22381646
TI  - The application of the Yerkes-Dodson law in a childhood weight management
      program: examining weight dissatisfaction.
AB  - OBJECTIVE: To determine the effect of dissatisfaction with one's weight on
      outcomes in a weight management program. METHODS: Participants included 149
      children between the ages of 11 and 14 years who were enrolled in an intensive
      weight loss intervention. All participants had a body mass index (BMI) >= 85th
      percentile. Children were divided into tertiles based on their level of weight
      dissatisfaction as assessed by the Kids' Eating Disorder Survey. RESULTS:
      Analysis revealed significant differences across levels of weight dissatisfaction
      categories for weight loss. Specifically, children in the moderate
      dissatisfaction group lost weight while participants in low and high groups
      gained weight over 6 months. CONCLUSION: As the Yerkes-Dodson law would predict,
      these findings suggest that moderate levels of weight dissatisfaction are
      associated with improved outcomes in a weight management program.

PMID- 22381648
TI  - Pacemaker lead failure masquerading as ventricular fibrillation.

PMID- 22381649
TI  - Concerns about safety of the AutoPulse use in treatment of pulmonary embolism.

PMID- 22381650
TI  - SOFA so good for predicting long-term outcomes.

PMID- 22381651
TI  - Endobronchial brachytherapy provides excellent long-term control of recurrent
      granulation tissue after tracheal stenosis.
AB  - PURPOSE: To review the experience of using endobronchial brachytherapy (EBB) as a
      treatment for recurrent tracheal granulation tissue. METHODS AND MATERIALS:
      Patients referred for EBB at the Rabin Medical Center for benign stenosis were
      reviewed with institutional review board approval. Patients underwent
      bronchoscopic resection of granulation tissue followed by insertion of self
      expanding metallic stents. After stenting, repeat laser resection was done at
      least 1 week before brachytherapy. After CT simulation, patients had three
      dimensional brachytherapy treatment planning. A single 10-Gy dose was prescribed
      to 1.0cm from the source and treatment was delivered using high-dose-rate
      afterloader with (192)Ir source. Patients were followedup with bronchoscopy every
      3 months after the completion of therapy. RESULTS: From November 2001 to January
      2009, 29 patients were treated with EBB to prevent granulation tissue
      reformation. Median age was 70 years and 55% of patients were male. Ninety
      percent of patients were treated to the trachea and the remaining patients had
      stenoses in the main stem bronchi. The primary cause of stenosis was prolonged
      mechanical ventilation (76%). The median time from stent placement to
      brachytherapy was 69 days. Median active length of treatment was 7cm. With a
      median followup of 36 months, 66% (19 of 29) of patients remained free of
      granulation tissue. Forty-eight percent of patients have died, with all except 1
      patient dying of their underlying condition. A single patient experienced death
      from tracheoesophageal fistula. CONCLUSION: EBB is an effective and safe
      treatment to prevent recurrent granulation tissue formation after endobronchial
      resection and should be considered in patients who are unable to undergo surgical
      resection.

PMID- 22381652
TI  - Comparison of survival and regional failure between accelerated partial breast
      irradiation and whole breast irradiation.
AB  - PURPOSE: To compare rates of regional recurrence (RR) and overall survival (OS)
      between a pooled set of 1400 patients treated on the American Society of Breast
      Surgeons MammoSite (Hologic, Inc., Bedford, MA) Registry Trial to a cohort of
      3600 patients treated with whole breast irradiation (WBI). METHODS AND MATERIALS:
      A total of 1440 women underwent accelerated partial breast irradiation (APBI)
      between 2002 and 2004 as part of the American Society of Breast Surgeons Registry
      Trial and a total of 3593 patients who received WBI were evaluated from the
      Surveillance Epidemiology and End Results database with treatment received
      between 1980 and 2009. A matched-pair analysis was performed based on age,
      receipt of hormonal therapy, chemotherapy, nodal status, and tumor size (1051
      patients per arm). Rates of RR and OS were then analyzed for each group. RESULTS:
      After the match, no differences in patient characteristics were noted when tumor
      size was evaluated as a continuous variable. Rates of RR and OS were similar
      between the WBI and APBI groups. A Cox regression model found no difference
      between WBI and APBI with regard to RR; however, OS was improved in the APBI
      cohort (hazard ratio 0.008, p<0.0001). CONCLUSIONS: With one of the largest
      patient populations to date comparing WBI and APBI, no difference in RR or OS was
      noted between WBI and APBI treatment. Until the publication of prospective Phase
      III trials, these data support the continued use of APBI on protocol and off
      protocol in appropriately selected patients.

PMID- 22381653
TI  - Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent
      graduates of North American thoracic residencies.
AB  - Minimally invasive surgical techniques offer several advantages over traditional
      open procedures, yet the pathway to minimally invasive proficiency can be
      difficult to navigate. As a part of an effort of the Joint Council of Thoracic
      Surgical Education to increase access to this skill set in the general thoracic
      community, recent graduates of thoracic residencies were surveyed to determine
      the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy
      proficiency and the merits of various educational opportunities. The objective of
      this study was to estimate the comfort level of recent graduates with the
      minimally invasive approach, as this demographic not only reflects the current
      status of training, but represents the future of the specialty. Surgeons
      graduating North American thoracic residencies between 2006 and 2008 identifying
      themselves as practitioners of general thoracic surgery were surveyed. A total of
      271 surgeons completed training between 2006 and 2008 and indicated general
      thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed).
      One hundred and forty-six surgeons completed the survey (54%) including 74 of 84
      (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform
      general thoracic procedures consider themselves proficient in VATS lobectomies
      (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P
      < 0.0001). Of surgeons considering themselves to be proficient at VATS
      lobectomies, 66% felt thoracic residency was critical or very important to
      achieving proficiency. Fellowships after completing board residency, animal labs,
      and follow-up VATS courses put on by experts were much less consistently
      beneficial. The vast majority of the 25 dedicated general thoracic surgeons who
      graduate each year consider themselves proficient in VATS lobectomies, largely
      due to training in their thoracic residencies. On the other hand, the minority of
      surgeons performing general thoracic procedures as a part of a mixed practice
      consider themselves proficient in VATS lobectomies. Further study is warranted to
      enhance the VATS lobectomy experience of mixed practice surgeons particularly
      during their thoracic residencies.

PMID- 22381655
TI  - Characterization of a wheat (Triticum aestivum L.) expansin gene, TaEXPB23,
      involved in the abiotic stress response and phytohormone regulation.
AB  - Expansins are proteins that are generally accepted to be key regulators of cell
      wall extension and plant growth. We examined the expression pattern of TaEXPB23,
      a wheat (Triticum aestivum L.) expansin gene, under exogenous phytohormone and
      abiotic stress treatments. In addition, we evaluated its function in the
      tolerance to salt stress and high temperature (HT) by overexpressing it in
      transgenic tobacco plants. In subcellular localization assays, TaEXPB23 localized
      to the cell wall. Expression analysis demonstrated that the transcription pattern
      of TaEXPB23 corresponded to wheat coleoptile growth. Real-time RT-PCR analysis
      revealed that TaEXPB23 transcript expression was upregulated by exogenous methyl
      jasmonate (MeJA) and salt stress, but downregulated by exogenous gibberellins
      (GA3), ethylene (ET), indole-3-acetic acid (IAA) and alpha-naphthlcetic acid
      (NAA). Overexpression of TaEXPB23 in tobacco (tabacum) conferred tolerance to
      salt stress by enhancing water retention ability (WRA) and decreasing osmotic
      potential (OP). However, transgenic plants overexpressing TaEXPB23 did not show
      any improvement in the tolerance to HT stress. These results suggested that
      TaEXPB23 is regulated by phytohormones and is involved in the regulation of salt
      stress tolerance.

PMID- 22381656
TI  - Interactions between light and growing season temperatures on, growth and
      development and gas exchange of Semillon (Vitis vinifera L.) vines grown in an
      irrigated vineyard.
AB  - High-light intensities and temperatures of the warm climate regions of Australia
      and elsewhere have a major effect on the growth and development of grapevines
      (Vitis vinifera L.). The objective of this research was to assess interactions
      between the light and seasonal temperatures by shading some vines and comparing
      these with vines exposed to high-light intensities. Canopy temperatures were
      monitored using infrared radiometers and budbreak, phenology, growth, yield,
      berry ripening and gas exchange determined over three growing seasons. Results
      showed canopies were generally about 4  degrees C cooler than air and shading
      extended this cooling. Irradiance, irrespective of seasonal temperatures, had no
      effect on time of budbreak, shoot phenology, stem growth, yield and bunch fresh
      weights while bunch and leaf dry weights were reduced in low-light. Bunch
      ripening was initially delayed by low-light but thereafter the ripening process
      was highly temperature-dependent. Rates increased linearly with increasing
      temperature in both low and high-light and were optimal at about 35  degrees C.
      Maximum photosynthetic capacity was impaired by low irradiance, in accordance
      with shade leaf attributes, and attributable to stomatal closure. No effects of
      the low photosynthetic capacity apparently carried-over to sugar accumulation,
      consistent with the strong sink capacity of bunches.

PMID- 22381657
TI  - Specialization of the sting venom and skin mucus of Cathorops spixii reveals
      functional diversification of the toxins.
AB  - Cathorops spixii is the most common venomous fish on the Brazilian coast. Apart
      from the involvement with defense against pathogens, the possible contribution of
      skin mucus components to the development of injuries caused by venomous fish
      species has not been investigated. Thus, the present study was conducted to gain
      a better understanding of the peptide and protein components of fish skin mucus
      and the sting venom from the catfish C. spixii. Our results show that sting venom
      and skin mucus have distinct constituents that distinguished them like structural
      proteins, chaperones, ion transport, carbohydrate metabolism, oxidoreductase,
      cell cycle and protein binding present in sting venom and like tropomyosin 3
      isoform 2 and energy metabolim proteins in skin mucus. But in a group of common
      13 proteins we identified and isolated a WAP65 protein. The peptide fractions
      caused more harmful effects, such as venular stasis, hemorrhage and changes in
      the arteriolar wall diameter, and the protein fractions produced a typical
      inflammatory process in post-capillary venules. And finally we showed for the
      first time the presence WAP65 in sting venom and skin mucus of C. spixii using
      LC/MS/MS and also we purified this protein in the sting venom. Wap65 shows
      inflammatory action, working at different doses inducing an increase in the
      number of leukocytes rolling and adhering to the endothelium.

PMID- 22381658
TI  - The Czech National Diamond-Blackfan Anemia Registry: clinical data and ribosomal
      protein mutations update.
AB  - Diamond-Blackfan anemia is a rare inherited bone marrow failure syndrome
      diagnosed in early infancy that is characterized by a (a) macrocytic anemia with
      no other significant cytopenia, (b) reticulocytopenia, and (c) normal bone marrow
      cellularity with a paucity of erythroid precursors. Physical anomalies are often
      present. Mutations in several ribosomal proteins have been associated with the
      disease. Here we present a detailed description of 39 patients from 34 families
      enrolled in the Czech National Diamond-Blackfan Anemia Registry. Erythrocyte
      adenosine deaminase activity and serum erythropoietin levels were measured and
      bone marrow analysis and clonogenic assays were carried out. Twenty-two different
      ribosomal proteins were sequenced. We identified mutations in five different
      ribosomal proteins in 28/39 patients (71.8%) from 23/34 families (67.6%). Several
      new mutations are described. The most interesting data relate to genotype
      phenotype correlations. All patients with ribosomal protein L5 or ribosomal
      protein L11 mutations have a thumb defect usually with one or more other
      anomalies. Most of these patients were born small for gestational age and
      currently have short stature. We also described five patients with a ribosomal
      protein S26 mutation. All of the latter are transfusion-dependent and they
      exhibit skeletal abnormalities rather than thumb or craniofacial deformities.
      Patients with ribosomal protein S19 seem to bear mildest associated anomalies,
      usually in a craniofacial region.

PMID- 22381659
TI  - Relative size of the eye and orbit: an evolutionary and craniofacial constraint
      model for examining the etiology and disparate incidence of juvenile-onset myopia
      in humans.
AB  - The principal aim of this research is to provide a new model for investigating
      myopia in humans, and contribute to an understanding of the degree to which
      modern variation and evolutionary change in orbital and overall craniofacial
      morphology may help explain the common eye form association with this condition.
      Recent research into long and short-term evolution of the human orbit reveals a
      number of changes in this feature, and particularly since the Upper Paleolithic.
      These include a reduction in orbital depth, a decrease in anterior projection of
      the upper and lower orbital margins, and most notably, a reduction in orbital
      volume since the Holocene in East Asia. Reduced orbital volume in this geographic
      region could exacerbate an existing trend in recent hominin evolution toward
      larger eyes in smaller orbits, and may help explain the unusually high frequency
      of myopia in East Asian populations. The objective of the current study is to
      test a null hypothesis of no relationship between a ratio of orbit to eye volume
      and spherical equivalent refractive error (SER) in a sample of Chinese adults,
      and examine how relative size of the eye within the orbit relates to SER between
      the sexes and across the sample population. Analysis of the orbit, eye, and SER
      reveals a strong relationship between relative size of the eye within the orbit
      and the severity of myopic refractive error. An orbit/eye ratio of 3 for females
      and 3.5 for males (or an eye that occupies approximately 34% and 29% of the
      orbit, respectively), designates a clear threshold at which myopia develops, and
      becomes progressively worse as the eye continues to occupy a greater proportion
      of the orbital cavity. These results indicate that relative size of the eye
      within the orbit is an important factor in the development of myopia, and
      suggests that individuals with large eyes in small orbits lack space for adequate
      development of ocular tissues, leading to compression and distortion of the
      lithesome globe within the confines of the orbital walls. The results of this
      study indicate that future research examining the etiology of juvenile-onset
      myopia, and particularly its correlation with ancestry, sex, age, and
      intelligence, should consider how the eye interacts with the matrix of structural
      and functional components of the skull during both ontogenetic and evolutionary
      morphogenesis.

PMID- 22381660
TI  - Functional electrical stimulation for stoke rehabilitation.

PMID- 22381661
TI  - The micron stroke hypothesis of Alzheimer's disease and dementia.
AB  - Alzheimer's disease as currently described in the medical literature is often
      more a description of dementia rather than a specific disease. In over a century
      of scientific work there has been no proven theory as to the precise pathogenesis
      of Alzheimer's disease and dementia. As there is no efficient treatment for
      patients with Alzheimer's disease, prevention or attenuation of the disease is of
      substantial value. An intricate collection of hypotheses, studies, research, and
      experience has made it complicated for one to completely understand this disease.
      The purpose of this hypothesis is to illustrate new concepts and work to link
      those concepts to the present understanding of an obscure disease. The search for
      a single unifying hypothesis on the etiology of Alzheimer's disease has been
      elusive. Many hypotheses associated to Alzheimer's disease have not survived
      their testing to become theory. Suggested here is that the elusive nature of
      etiology of dementia is not from one cause, but rather the causes are numerous.
      Medical terminology used freely for decades is rarely evaluated in the light of a
      new hypothesis. At the foundation of this work is the suggestion of a new medical
      term: Micron Strokes. The Micron Stroke Hypothesis of Alzheimer's Disease and
      Dementia include primary and secondary factors. The primary factors can be
      briefly described as baseline brain tissue, atrial fibrillation, hypercoaguable
      state, LDL, carotid artery stenosis, tobacco exposure, hypertension diabetes
      mellitus, and the presence of systemic inflammation. Dozens of secondary factors
      contribute to the development of dementia. Most dementia is caused by nine
      primary categories of factors as they interact to cause micron strokes to the
      brain.

PMID- 22381662
TI  - Influence of heart rate and phase of the cardiac cycle on the occurrence of
      motion artifact in dual-source CT angiography of the coronary arteries.
AB  - BACKGROUND: Coronary CT angiography allows visualization of the coronary
      arteries. However, motion artifact can impair delineation of the coronary artery
      lumen and detection of coronary artery stenoses. OBJECTIVE: We investigated the
      influence of heart rate and the segment of the cardiac cycle during which images
      are reconstructed on the occurrence of motion artifacts. METHODS: We evaluated
      coronary CT angiography datasets obtained by 64-slice dual-source CT in 100
      consecutive patients. Data were reconstructed at 13 time instants during the
      cardiac cycle and evaluated for the presence of motion artifact. RESULTS: Mean
      heart rate was 66+/-14 beats/min. Overall, 98 of 100 patients had evaluable
      datasets. For heart rates <=60 beats/min, optimal image quality was uniformly
      found during late diastole (100% of cases with evaluable image quality during a
      time window between 65% and 75% of the cardiac cycle). With increasing heart
      rates, images reconstructed during late systole more frequently provided best
      image quality. However, image reconstruction could not be restricted to a
      systolic time period. To achieve evaluable image quality in 95% of cases, data
      acquired between 25% and 75% of the cardiac cycle had to be available for
      patients with heart rates >60 beats/min. CONCLUSION: Dual-source CT provides high
      image quality across a wide range of heart rates. Although data acquisition may
      be limited to diastole for patients with heart rates <=60 beats/min, the
      availability of data acquired both during systole and diastole is necessary for
      patients with higher heart rates.

PMID- 22381663
TI  - Low radiation coronary calcium scoring by dual-source CT with tube current
      optimization based on patient body size.
AB  - BACKGROUND: Reducing tube voltage from 120 kV to 100 kV during noncontrast CT for
      the detection of coronary artery calcium reduces patient radiation exposure.
      OBJECTIVE: We investigated whether coronary calcium scoring by multidetector row
      CT can be performed at reduced tube current, resulting in lower radiation dose to
      the patient. METHODS: Sixty-six outpatients were scanned on the same visit by
      dual-source CT (DSCT) with a standard protocol (120 kVp, 150 mAs), followed by a
      scan with reduced tube current: 85 mAs for patients with body mass index (BMI) <=
      30 kg/m(2) and weight <= 85 kg, and 120 mAs for patients with BMI > 30 kg/m(2) or
      weight > 85 kg. Low-dose scans were scored by an experienced reader blinded to
      the standard scan. RESULTS: Agatston scores (ASs) and calcium volume for standard
      versus low-dose scans were 236 +/- 581 versus 234 +/- 586 (P = 0.65, NS), and 189
      +/- 460 mm(3) versus 184 +/- 455 mm(3) with excellent correlation (r = 1.0, P <
      0.0001), and no significant difference (P = 0.14, NS). Effective radiation dose
      for the low-dose protocol (1.0 +/- 0.2 mSv) was significantly lower than for the
      standard protocol (1.7 +/- 0.2 mSv; P < 0.0001). Image noise was higher for the
      low-dose scan (18.8 +/- 5.5 HU vs 15.2 +/- 4.8 HU; P < 0.0001), but both were
      within target limits. CONCLUSION: Noncontrast CT for measurement of coronary
      artery calcium with lower tube current optimized for patient body size is
      equivalent to standard methods at 40% lower radiation dose, indicating that
      radiation dose can be lowered for coronary calcium scanning.

PMID- 22381664
TI  - [Congenital laryngeal cyst: an uncommon cause of stridor in neonates].
AB  - Laryngeal cyst is a rare but generally benign lesion in the larynx. It may cause
      stridor and life-threatening airway obstruction in early infancy. We report the
      case of a neonate who developed respiratory distress 24h after birth in relation
      with materno-fetal infection. Airway obstruction was then suspected because of
      stridor. A laryngeal mass was discovered at the time of intubation. The infant
      experienced a nosocomial infection and died on day 14 of life before any surgical
      treatment. Autopsy concluded in an epiglottic congenital laryngeal cyst.

PMID- 22381665
TI  - [Neonatal infection with Stenotrophomonas maltophilia (2 case studies)].
AB  - INTRODUCTION: Stenotrophomonas maltophilia (S.M.) is a Gram-negative bacillus,
      naturally resistant to cephalosporins and carbapenems, which can colonize
      different sites and may be responsible for serious infections for which treatment
      is a real challenge. We report 2 cases of nosocomial S.M. infection in 2
      hospitalized newborns in the neonatal intensive care unit. CASE 1: A 3-day-old
      newborn presented with infection beginning in the respiratory system, treated
      with ciprofloxacin, and complicated by septicemia, resulting in death. CASE 2: An
      11-day-old newborn presented with brain S.M. suppuration: empyema and multiple
      abscesses were treated successfully with the combination of amikacin and
      chloramphenicol with good progression in the short and medium terms. DISCUSSION:
      Some epidemiological studies report that S.M. is the second Gram-negative
      bacillus responsible for nosocomial infection after Klebsiella pneumoniae. While
      the respiratory location of the bacterium is typical, cerebral parenchyma damage
      is rare in the newborn. The treatment remains very delicate and difficult because
      of this bacterium's drug multiresistance. CONCLUSION: These 2 cases of infection
      caused by S.M. including respiratory tract infection with bacteremia and cerebral
      suppuration in newborns have broadened the spectrum of diseases caused by this
      organism and are a reminder of the emergence of this organism and its natural
      resistance to several antibiotics.

PMID- 22381666
TI  - [Allergic and non-allergic hypersensitivity to non-opioid analgesics,
      antipyretics and nonsteroidal anti-inflammatory drugs in children: epidemiology,
      clinical aspects, pathophysiology, diagnosis and prevention].
AB  - Non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs are
      widely used, but suspected allergic reactions to these drugs are rare, especially
      in children. Most frequent reactions are cutaneous (urticaria, angioedema) and
      respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful
      toxidermias) are rare. In a few patients, reactions may result from a specific
      (allergic) hypersensitivity, with positive responses in prick and intradermal
      tests (anaphylaxis, immediate urticaria and/or angioedema) and in intradermal and
      patch tests (non-immediate reactions). However, most reactions result from a non
      specific (non-allergic) hypersensitivity (intolerance), with a frequent cross
      reactivity between the various families of analgesics, antipyretics and
      nonsteroidal anti-inflammatory drugs, including paracetamol. Based on a
      convincing clinical history and/or positive responses in challenge tests,
      intolerance to non-opioid analgesics, antipyretics and nonsteroidal anti
      inflammatory drugs has been diagnosed in 13 to 50% of the patients with allergic
      like reactions to these drugs. Risk factors are a personal atopy and age.
      Prevention is based on administration of other (families of) analgesics,
      antipyretics and nonsteroidal anti-inflammatory drugs in patients with allergic
      hypersensitivity to these drugs. In patients with non-allergic hypersensitivity,
      prevention is based on administration of drugs with a low cyclo-oxygenase-1
      inhibitory activity (if tolerated). Desensitization is efficient in patients with
      respiratory reactions, but does not work in patients with mucocutaneous reactions
      and anaphylaxis.

PMID- 22381667
TI  - [Congenital pulmonary lymphangiectasis: an unusual cause of respiratory distress
      in neonates].
AB  - Congenital pulmonary lymphangiectasis (CPL) is a rare condition in neonates
      characterized by abnormal dilatation of the lymphatics draining the interstitial
      and subpleural spaces of the lungs. Diagnosis is difficult in the neonatal period
      because respiratory features and radiological findings are not specific of the
      disease. Definitive diagnosis of CPL can be made only by pathologic examinations.
      We report a case of a male near-term neonate presenting with severe respiratory
      distress at birth. The initial chest X-ray showed frosted glass-like infiltrates
      with air bronchogram suggesting a maternofetal infection or respiratory distress
      syndrome. The infant required mechanical ventilation and chest tube insertion for
      right then bilateral pneumothorax. The child died 15 days later in spite of
      optimal high-frequency ventilation, bilateral pneumothorax drainage, and
      hemodynamic support. Autopsy revealed features consistent with the diagnosis of
      CPL. Although CPL is very rare, we should be aware that it is a possible cause of
      severe unexplained respiratory distress in neonates.

PMID- 22381668
TI  - [Spontaneous neonatal arterial thrombosis: a report of 4 neonates].
AB  - Arterial thromboses are rare in newborns, mostly caused by arterial catheters.
      Neonatal arterial thrombosis occurring in other contexts is much rare. We report
      arterial thrombosis, not caused by catheterisation in 4 neonates hospitalised in
      the neonatology department of the Farhat Hached de Sousse hospital in Tunisia.
      The diagnosis of arterial thrombosis was made based on signs of ischemia in 2
      patients affected by thrombosis of the iliac arteries. The symptoms were less
      clear: anuria associated with arterial high blood pressure in 1 patient affected
      by thrombosis of the abdominal aorta and by anuria with melena in a newborn with
      aortic and mesenteric thrombosis. Diagnosis was confirmed by Doppler sonography
      in 3 patients and based on autopsy data in 1 patient. A delay to consultation was
      noted in 3 patients, whose outcome was fatal. The progression was favourable
      after thrombolysis and anticoagulation using heparin in 1 patient with major
      aortic thrombosis. A review of the literature on the epidemiological, clinical,
      therapeutic and outcome data of the arterial thrombosis in the newborn child is
      provided.

PMID- 22381669
TI  - [Risk factors for developing pneumothorax in full-term neonates with respiratory
      distress].
AB  - OBJECTIVES: To describe respiratory distress (RD) in full-term neonates
      hospitalized in the NICU and to determine risk factors in this population for
      pneumothorax. STUDY DESIGN: Retrospective inclusion for 4 years of full-term
      neonates hospitalized for RD before the 2nd day of life. Neonates were separated
      into Group I (RD with no pneumothorax) and Group II (RD with pneumothorax). Data
      collected from maternal and newborn medical records were obstetrical, perinatal,
      and postnatal. P<0.05 was set as the significance level. RESULTS: Ninety-six
      neonates were included. In this population, 64 (66.7%) were male, 45 (46.9%) were
      born by cesarean section, and 30 (31.3%) by elective cesarean section. Neonatal
      outcome was 4.6 days of hospital stay, 47.4% odds of mechanical ventilation, and
      17.7% of persistent pulmonary hypertension of the neonate (PPHN). A central
      catheter was needed in 25% of the patients and amine treatment in 3.1%. The
      number of neonates born by cesarean section was lower as term increased. Those
      born by cesarean section were more likely to develop PPHN (26.7 vs 9.8%; P=0.03),
      and those born without labor were more likely to require oxygen (83.3 vs 63.6%;
      P=0.05). When comparing Group I and Group II (32 neonates), absence of labor (RR
      1.5) and birth outside of a level III maternity unit (RR 1.6) were risk factors
      for pneumothorax. These results were confirmed in multivariate analysis. In Group
      II, birth before 39 weeks was a risk factor for bilateral pneumothorax (P=0.01).
      The median length of hospitalization was significantly longer in Group II than in
      Group I (5.8 days vs 4 days, P=0.03). CONCLUSIONS: RD at term exposes the infant
      to high morbidity and pneumothorax, especially if born outside of a level III
      maternity unit and absence of labor.

PMID- 22381670
TI  - Bullous pemphigoid in a transplant recipient: is this a sign of allograft
      rejection?

PMID- 22381671
TI  - Non-curative gastrectomy for metastatic gastric cancer: rationale and long-term
      outcome in multicenter settings.
AB  - BACKGROUND: Metastatic gastric cancer remains a significant problem as the
      majority of Western patients are diagnosed with disseminated disease and no
      routine therapeutic regimen is accepted in such cases. METHODS: A cohort of 3141
      patients with gastric cancer operated between 1990 and 2005 was evaluated using a
      multicenter data set held by the Polish Gastric Cancer Study Group to determine
      potential risks and benefits of non-curative gastrectomy for metastatic disease.
      Additionally, parameters of Quality of Life (QoL) were evaluated prospectively in
      140 patients undergoing gastrectomy using the QLQ-C30 questionnaire. RESULTS:
      Gastrectomy was carried out in 2258 patients. Distant organ metastases were
      diagnosed in 951 patients, 415 of which underwent non-curative gastrectomy. The
      overall mortality rates were significantly higher in patients undergoing non
      resectional surgery (10%) than either curative (3%, P < 0.001) or non-curative
      (4%, P = 0.002) gastrectomy. The overall median survival in patients with
      metastatic disease was significantly higher for non-curative gastrectomy (10.6
      months, 95% confidence interval (CI) 9.3-11.9) than for non-resective operations
      (4.4 months, 95% CI 4.0 to 4.8, P < 0.001). The hazard ratio of death in patients
      subject to non-resectional surgery compared to those treated by gastrectomy was
      2.923 (95% CI 2.473 to 3.454, P < 0.001). A gradual impairment in QoL parameters
      was found over 12 months after non-curative resections but changes did not reach
      statistical significance and individual parameters were similar to gastrectomy
      without distant metastases. CONCLUSION: Non-curative gastrectomy for metastatic
      gastric cancer is associated with significantly better survival compared to non
      resective surgery and does not impair quality of life.

PMID- 22381672
TI  - Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with
      alpha1-adrenoceptor affinities.
AB  - An association between alpha(1)-adrenoceptor affinities, hERG K(+)-antagonistic
      properties and antiarrhythmic activities for a series of phenylpiperazine
      derivatives of hydantoin (2a-21a) was investigated. New compounds were
      synthesized and tested for their affinity for alpha(1)-adrenoceptors in
      radioligand binding assay using [(3)H]-prazosin as a selective radioligand.
      Antiarrhythmic activities in adrenaline- and barium chloride-induced arrhythmia
      models, an influence of the phenylpiperazine derivatives on the ECG-components
      and blood pressure were tested in vivo in normotensive rats. The hERG K(+)
      antagonistic properties of the most potent antiarrhythmic agents were
      investigated in silico by the use of program QikProp. The highest alpha(1)
      adrenoceptor affinity (K(i)=4.7 nM) and the strongest antiarrhythmic activity in
      adrenaline induced arrhythmia (ED(50)=0.1 mg/kg) was found for 1-(4-(4-(2
      methoxyphenyl)piperazin-1-yl)butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione
      hydrochloride (19a). The results indicated a significant correlation between
      alpha(1)-AR affinities (pK(i)) and antiarrhythmic activity (ED(50)) in adrenaline
      model (R(2)=0.92, p <0.005). Influence of the examined phenylpiperazine hydantoin
      derivatives on hERG K(+) channel, predicted by means of in silico methods,
      suggested their hERG K(+)-blocking properties.

PMID- 22381673
TI  - Does reduced glomerular filtration rate equate to chronic kidney disease?

PMID- 22381675
TI  - Effect of screening on deaths from cervical cancer in Sweden.

PMID- 22381674
TI  - Cardiovascular disease in kidney donors: matched cohort study.
AB  - OBJECTIVE: To determine whether people who donate a kidney have an increased risk
      of cardiovascular disease. DESIGN: Retrospective population based matched cohort
      study. PARTICIPANTS: All people who were carefully selected to become a living
      kidney donor in the province of Ontario, Canada, between 1992 and 2009. The
      information in donor charts was manually reviewed and linked to provincial
      healthcare databases. Matched non-donors were selected from the healthiest
      segment of the general population. A total of 2028 donors and 20,280 matched non
      donors were followed for a median of 6.5 years (maximum 17.7 years). Median age
      was 43 at the time of donation (interquartile range 34-50) and 50 at the time of
      follow-up (42-58). MAIN OUTCOME MEASURES: The primary outcome was a composite of
      time to death or first major cardiovascular event. The secondary outcome was time
      to first major cardiovascular event censored for death. RESULTS: The risk of the
      primary outcome of death and major cardiovascular events was lower in donors than
      in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95%
      confidence interval 0.48 to 0.90). The risk of major cardiovascular events
      censored for death was no different in donors than in non-donors (1.7 v 2.0
      events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all
      sensitivity analyses. Older age and lower income were associated with a higher
      risk of death and major cardiovascular events in both donors and non-donors when
      each group was analysed separately. CONCLUSIONS: The risk of major cardiovascular
      events in donors is no higher in the first decade after kidney donation compared
      with a similarly healthy segment of the general population. While we will
      continue to follow people in this study, these interim results add to the
      evidence base supporting the safety of the practice among carefully selected
      donors.

PMID- 22381676
TI  - Effects of gestational age at birth on health outcomes at 3 and 5 years of age:
      population based cohort study.
AB  - OBJECTIVE: To investigate the burden of later disease associated with
      moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth. DESIGN:
      Secondary analysis of data from the Millennium Cohort Study (MCS). SETTING:
      Longitudinal study of infants born in the United Kingdom between 2000 and 2002.
      PARTICIPANTS: 18,818 infants participated in the MCS. Effects of gestational age
      at birth on health outcomes at 3 (n = 14,273) and 5 years (n = 14,056) of age
      were analysed. MAIN OUTCOME MEASURES: Growth, hospital admissions, longstanding
      illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating
      of their children's health. RESULTS: Measures of general health, hospital
      admissions, and longstanding illness showed a gradient of increasing risk of
      poorer outcome with decreasing gestation, suggesting a "dose-response" effect of
      prematurity. The greatest contribution to disease burden at 3 and 5 years was in
      children born late/moderate preterm or early term. Population attributable
      fractions for having at least three hospital admissions between 9 months and 5
      years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks
      and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to
      6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%),
      5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at
      5 years were attributed to very preterm birth, moderate/late preterm birth, and
      early term birth. CONCLUSIONS: These results suggest that health outcomes of
      moderate/late preterm and early term babies are worse than those of full term
      babies. Additional research should quantify how much of the effect is due to
      maternal/fetal complications rather than prematurity itself. Irrespective of the
      reason for preterm birth, large numbers of these babies present a greater burden
      on public health services than very preterm babies.

PMID- 22381677
TI  - Screening and cervical cancer cure: population based cohort study.
AB  - OBJECTIVE: To determine whether detection of invasive cervical cancer by
      screening results in better prognosis or merely increases the lead time until
      death. DESIGN: Nationwide population based cohort study. SETTING: Sweden.
      PARTICIPANTS: All 1230 women with cervical cancer diagnosed during 1999-2001 in
      Sweden prospectively followed up for an average of 8.5 years. MAIN OUTCOME
      MEASURES: Cure proportions and five year relative survival ratios, stratified by
      screening history, mode of detection, age, histopathological type, and FIGO
      (International Federation of Gynecology and Obstetrics) stage. RESULTS: In the
      screening ages, the cure proportion for women with screen detected invasive
      cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was
      66% (62% to 70%), a statistically significant difference in cure of 26% (16% to
      36%). Among symptomatic women, the cure proportion was significantly higher for
      those who had been screened according to recommendations (interval cancers) than
      among those overdue for screening: difference in cure 14% (95% confidence
      interval 6% to 23%). Cure proportions were similar for all histopathological
      types except small cell carcinomas and were closely related to FIGO stage. A
      significantly higher cure proportion for screen detected cancers remained after
      adjustment for stage at diagnosis (difference 15%, 7% to 22%). CONCLUSIONS:
      Screening is associated with improved cure of cervical cancer. Confounding cannot
      be ruled out, but the effect was not attributable to lead time bias and was
      larger than what is reflected by down-staging. Evaluations of screening
      programmes should consider the assessment of cure proportions.

PMID- 22381678
TI  - Extra cytoplasmic function sigma factor activation.
AB  - The bacterial cell envelope is essential for cell viability and is a target for
      numerous antibiotics and host immune defenses. Thus bacteria must sense and
      respond to damage to the cell envelope. Many bacteria utilize alternative sigma
      factors such as extracytoplasmic function (ECF) sigma factors to respond to cell
      envelope stress. Although ECF sigma factors are utilized by both Gram negative
      and Gram positive bacteria to respond to cell envelope stress, the mechanisms of
      sensing differ. In this review, we examine the events and proteins that are
      required for activation of two model extracytoplasmic function sigma factors,
      sigma(E) in E. coli and sigma(W) in B. subtilis.

PMID- 22381679
TI  - Mutualism meltdown in insects: bacteria constrain thermal adaptation.
AB  - Predicting whether and how organisms will successfully cope with climate change
      presents critical questions for biologists and environmental scientists. Models
      require knowing how organisms interact with their abiotic environment, as well
      understanding biotic interactions that include a network of symbioses in which
      all species are embedded. Bacterial symbionts of insects offer valuable models to
      examine how microbes can facilitate and constrain adaptation to a changing
      environment. While some symbionts confer plasticity that accelerates adaptation,
      long-term bacterial mutualists of insects are characterized by tight lifestyle
      constraints, genome deterioration, and vulnerability to thermal stress. These
      essential bacterial partners are eliminated at high temperatures, analogous to
      the loss of zooanthellae during coral bleaching. Recent field-based studies
      suggest that thermal sensitivity of bacterial mutualists constrains insect
      responses. In this sense, highly dependent mutualisms may be the Achilles' heel
      of thermal responses in insects.

PMID- 22381680
TI  - Alteration of lipids and the transcription of lipid-related genes in
      myelodysplastic syndromes via a TP53-related pathway.
AB  - Myelodysplastic syndromes (MDS) are clonal stem cell diseases of the bone marrow
      characterized by abnormalities in maturation of hematopoietic cells of all
      lineages. MDS patients frequently have lower lipids and high rates of apoptosis
      and p53 (TP53) expression. An association between the reduced lipids in MDS and
      the expression of lipid-related genes was sought. We further evaluated whether 3
      hydroxy-3-methyl-glutaryl-CoA reductase (HMGcoAR) and low-density lipoprotein
      receptor (LDL-R) are regulated by TP53 in vivo and in vitro. Gene expression was
      measured using real-time reverse transcription polymerase chain reaction on RNA
      extracted from bone marrow and peripheral blood from eight newly diagnosed MDS
      patients and eight controls and from mice livers. Serum lipid profile was
      measured using colorimetric enzymatic procedures. Total- and LDL cholesterol were
      lower in MDS patients in comparison to controls (p = 0.04 and p = 0.01,
      respectively). HMGcoAR messenger RNA increased in peripheral blood and bone
      marrow of MDS patients compared to controls (p = 0.04 and p = 0.01,
      respectively). LDL-R messenger RNA was higher only in the peripheral blood of MDS
      patients (p = 0.05). Comparable results were obtained in vivo. The transcription
      of these genes correlates with TP53 activation as documented by p21 messenger RNA
      elevation, a surrogate for TP53 activation and by using TP53 temperature
      sensitive cells treated with adriamycin. To conclude, an association between
      reduced lipids in MDS and expression of HMGcoAR and LDL-R genes was documented.
      The transcription of these genes can be regulated by TP53.

PMID- 22381681
TI  - Panobinostat (LBH589)-induced acetylation of tubulin impairs megakaryocyte
      maturation and platelet formation.
AB  - Drug-induced thrombocytopenia often results from dysregulation of normal
      megakaryocytopoiesis. In this study, we investigated the mechanisms responsible
      for thrombocytopenia associated with the use of Panobinostat (LBH589), a histone
      deacetylase inhibitor with promising anti-cancer activities. The effects of
      LBH589 were tested on the cellular and molecular aspects of megakaryocytopoiesis
      by utilizing an ex vivo system in which mature megakaryocytes (MK) and platelets
      were generated from human primary CD34(+) cells. We demonstrated that LBH589 did
      not affect MK proliferation or lineage commitment but inhibited MK maturation and
      platelet formation. Although LBH589 treatment of primary MK resulted in
      hyperacetylation of histones, it did not interfere with the expression of genes
      that play important roles during megakaryocytopoiesis. Instead, we found that
      LBH589 induced post-translational modifications of tubulin, a nonhistone protein
      that is the major component of the microtubule cytoskeleton. We then demonstrated
      that LBH589 treatment induced hyperacetylation of tubulin and alteration of
      microtubule dynamics and organization required for proper MK maturation and
      platelet formation. This study provides new insights into the mechanisms
      underlying LBH589-induced thrombocytopenia and provides a rationale for using
      tubulin as a target for selective histone deacetylase inhibitor therapies to
      treat thrombocytosis in patients with myeloproliferative neoplasms.

PMID- 22381682
TI  - A real-time (PCR) for a real life...? Quantitative evaluation of BCL2/IGH in
      follicular lymphoma and its implications for clinical practice.
AB  - Follicular lymphoma (FL) is highly associated with the molecular rearrangement
      BCL2/IGH. Although BCL2/IGH has been studied many times in follicular lymphoma,
      its real clinical value remains controversial. In this study, we performed
      quantitative testing by real-time polymerase chain reaction in 56 FL patients
      with median follow-up of 44 months (range, 9-102 months); chemotherapy was
      administered in 52 of 56 cases. Pretreatment numbers of BCL2/IGH varied in wide
      ranges, with a median of 2947 (range, 0-1,261,013) copies/10(6) cellular
      equivalent in peripheral blood (PB) and 4650 copies/10(6) cellular equivalent
      (range, 1-1,056,813) in bone marrow (BM), the difference between PB and BM was
      significant (p = 0.006). Pretreatment of BCL2/IGH quantities were correlated to
      clinical parameters (e.g., age, stage, sex, lactate dehydrogenase, B symptoms,
      grade, bulky disease, chemotherapy regimen) and to progression free-survival.
      Advanced clinical stage (III and IV) and microscopic BM involvement were
      significantly associated with higher numbers of BCL2/IGH in PB (p < 0.05) and in
      BM (p = 0.05), regardless all or newly diagnosed patients were evaluated. High
      pretreatment burden of BCL2/IGH was associated with significantly shorter
      progression-free survival; p = 0.003 and p = 0.047 for PB and BM, respectively.
      In conclusion, pretreatment quantity of BCL2/IGH in PB or BM seems to mirror the
      extent of disease and can provide an auxiliary prognostic parameter in FL. Our
      results also support evidence of the negative prognostic value of microscopic BM
      involvement in FL.

PMID- 22381683
TI  - The role of local food availability in explaining obesity risk among young school
      aged children.
AB  - In recent years, research and public policy attention has increasingly focused on
      understanding whether modifiable aspects of the local food environment - the
      types and composition of food outlets families have proximate access to - are
      drivers of and potential solutions to the problem of childhood obesity in the
      United States. Given that much of the earlier published research has documented
      greater concentrations of fast-food outlets alongside limited access to large
      grocery stores in neighborhoods with higher shares of racial/ethnic minority
      groups and residents living in poverty, differences in retail food contexts may
      indeed exacerbate notable child obesity disparities along socioeconomic and
      racial/ethnic lines. This paper examines whether the lack of access to more
      healthy food retailers and/or the greater availability of "unhealthy" food
      purveyors in residential neighborhoods explains children's risk of excessive
      weight gain, and whether differential food availability explains obesity
      disparities. I do so by analyzing a national survey of U.S. children followed
      over elementary school (Early Childhood Longitudinal Study - Kindergarten Cohort)
      who are linked to detailed, longitudinal food availability measures from a
      comprehensive business establishment database (the National Establishment Time
      Series). I find that children who live in residentially poor and minority
      neighborhoods are indeed more likely to have greater access to fast-food outlets
      and convenience stores. However, these neighborhoods also have greater access to
      other food establishments that have not been linked to increased obesity risk,
      including large-scale grocery stores. When examined in a multi-level modeling
      framework, differential exposure to food outlets does not independently explain
      weight gain over time in this sample of elementary school-aged children.
      Variation in residential food outlet availability also does not explain
      socioeconomic and racial/ethnic differences. It may thus be important to
      reconsider whether food access is, in all settings, a salient factor in
      understanding obesity risk among young children.

PMID- 22381685
TI  - How good are we when it comes to measuring creatinine in different patient
      populations?

PMID- 22381686
TI  - Prevalence and molecular characterization of Anaplasmataceae agents in free
      ranging Brazilian marsh deer (Blastocerus dichotomus).
AB  - Anaplasmataceae organisms comprise a group of obligate intracellular gram
      negative, tick-borne bacteria that can infect both animals and humans. In the
      present work we investigate the presence of Ehrlichia, Anaplasma, and
      Neorickettsia species in blood samples from Brazilian marsh deer (Blastocerus
      dichotomus), using both molecular and serologic techniques. Blood was collected
      from 143 deer captured along floodplains of the Parana River, near the Porto
      Primavera hydroelectric power plant. Before and after flooding, marsh deer were
      captured for a wide range research program under the financial support of Sao
      Paulo State Energy Company (CESP), between 1998 and 2001. Samples were divided
      into four groups according to time and location of capture and named MS01 (n=99),
      MS02 (n=18) (Mato Grosso do Sul, before and after flooding, respectively), PX
      (n=9; Peixe River, after flooding), and AGUA (n=17; Aguapei River, after
      flooding). The seroprevalences for Ehrlichia chaffeensis and Anaplasma
      phagocytophilum were 76.76% and 20.2% in MS01, 88.88% and 5.55% in MS02, 88.88%
      and 22.22% in PX, and 94.12% and 5.88% in AGUA, respectively. Sixty-one animals
      (42.65% of the total population) were PCR-positive for E. chaffeensis PCR (100.0%
      identity based on 16S rRNA, dsb, and groESL genes). Seventy deer (48.95% of the
      total population) were PCR-positive for Anaplasma spp. (99.0% of identity with A.
      platys, and in the same clade as A. phagocytophilum, A. bovis, and A. platys
      based on 16S rRNA phylogenetic analysis). Our results demonstrate that Brazilian
      marsh deer are exposed to E. chaffeensis and Anaplasma spp. and may act as
      reservoirs for these rickettsial agents, playing a role in disease transmission
      to humans and other animals.

PMID- 22381684
TI  - Subjective social status and psychosocial and metabolic risk factors for
      cardiovascular disease among African Americans in the Jackson Heart Study.
AB  - Subjective social status has been shown to be inversely associated with multiple
      cardiovascular risk factors, independent of objective social status. However, few
      studies have examined this association among African Americans and the results
      have been mixed. Additionally, the influence of discrimination on this
      relationship has not been explored. Using baseline data (2000-2004) from the
      Jackson Heart Study, an African American cohort from the U.S. South (N=5301), we
      quantified the association of subjective social status with selected
      cardiovascular risk factors: depressive symptoms, perceived stress, waist
      circumference, insulin resistance and prevalence of diabetes. We contrasted the
      strength of the associations of these outcomes with subjective versus objective
      social status and examined whether perceived discrimination confounded or
      modified these associations. Subjective social status was measured using two 10
      rung "ladders," using the U.S. and the community as referent groups. Objective
      social status was measured using annual family income and years of schooling
      completed. Gender-specific multivariable linear and logistic regression models
      were fit to examine associations. Subjective and objective measures were weakly
      positively correlated. Independent of objective measures, subjective social
      status was significantly inversely associated with depressive symptoms (men and
      women) and insulin resistance (women). The associations of subjective social
      status with the outcomes were modest and generally similar to the objective
      measures. We did not find evidence that perceived racial discrimination strongly
      confounded or modified the association of subjective social status with the
      outcomes. Subjective social status was related to depressive symptoms but not
      consistently to stress or metabolic risk factors in African Americans.

PMID- 22381688
TI  - Exploring the application of stem cells in tendon repair and regeneration.
AB  - PURPOSE: To conduct a systematic review of the current evidence for the effects
      of stem cells on tendon healing in preclinical studies and human studies.
      METHODS: A systematic search of the PubMed, CINAHL (Cumulative Index to Nursing
      and Allied Health Literature), Cochrane, and Embase databases was performed for
      stem cells and tendons with their associated terminology. Data validity was
      assessed, and data were collected on the outcomes of trials. RESULTS: A total of
      27 preclinical studies and 5 clinical studies met the inclusion criteria.
      Preclinical studies have shown that stem cells are able to survive and
      differentiate into tendon cells when placed into a new tendon environment,
      leading to regeneration and biomechanical benefit to the tendon. Studies have
      been reported showing that stem cell therapy can be enhanced by molecular
      signaling adjunct, mechanical stimulation of cells, and the use of augmentation
      delivery devices. Studies have also shown alternatives to the standard method of
      bone marrow-derived mesenchymal stem cell therapy. Of the 5 human studies, only 1
      was a randomized controlled trial, which showed that skin-derived tendon cells
      had a greater clinical benefit than autologous plasma. One cohort study showed
      the benefit of stem cells in rotator cuff tears and another in lateral
      epicondylitis. Two of the human studies showed how stem cells were successfully
      extracted from the humerus and, when tagged with insulin, became tendon cells.
      CONCLUSIONS: The current evidence shows that stem cells can have a positive
      effect on tendon healing. This is most likely because stem cells have
      regeneration potential, producing tissue that is similar to the preinjury state,
      but the results can be variable. The use of adjuncts such as molecular signaling,
      mechanical stimulation, and augmentation devices can potentially enhance stem
      cell therapy. Initial clinical trials are promising, with adjuncts for stem cell
      therapy in development.

PMID- 22381687
TI  - Reliability of early postoperative radiographic assessment of tunnel placement
      after anterior cruciate ligament reconstruction.
AB  - PURPOSE: To evaluate the interobserver and intraobserver reliability of
      radiographic assessment of tunnel placement in anterior cruciate ligament
      reconstruction. METHODS: Seven sports fellowship-trained orthopaedic surgeons in
      the Multicenter Orthopaedic Outcomes Network (MOON) group participated in the
      study. We prospectively enrolled 54 consecutive patients after primary anterior
      cruciate ligament reconstruction. Postoperative plain radiographs were obtained
      including a full-extension anteroposterior view of the knee, a lateral view of
      the knee in full extension, and a notch view at 45 degrees  of flexion (Rosenberg
      view). Three blinded reviewers performed 8 different radiographic measurements
      including those of Harner and Aglietti/Jonsson. Intraclass correlation
      coefficients were used to determine reliability of the measurements. Intrarater
      reliability was assessed by repeated measurements of a subset of 20 patient
      images from 1 institution, and inter-rater reliability was assessed by use of all
      54 sets of films from a total of 4 institutions. RESULTS: Intraobserver
      reliability for femoral measures ranged from none to substantial, with notch
      height having the worst results. Intraobserver reliability was moderate to almost
      perfect for tibial measures. Interobserver reliability ranged from slight to
      moderate for femoral measures. The Harner method for determining tunnel depth was
      more reliable than the Aglietti/Jonsson method. Interobserver reliability for
      tibial measures ranged from fair to substantial. The presence of metal
      interference screws did not improve reliability of measurements. CONCLUSIONS:
      Postoperative radiographs are easily obtained, but our results show that
      radiographic measurements are of quite variable reliability, with most of the
      results falling into the fair to moderate categories.

PMID- 22381689
TI  - Arthroscopic evaluation of preserved ligament remnant after selective
      anteromedial or posterolateral bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results and
      morphology of the preserved bundle remnants by second-look arthroscopy
      postoperatively 1 year after selective anteromedial (AM) or posterolateral (PL)
      bundle ACL reconstruction. METHODS: Between July 2004 and September 2009, 1,000
      patients underwent arthroscopic anterior cruciate ligament (ACL) reconstruction
      at our hospital. Among them, 20 (2%) underwent selective AM bundle (group A) or
      PL bundle (group P) ACL reconstruction surgery with hamstring tendon autografts.
      At 1 year after surgery, 19 patients (7 male and 12 female patients; age range,
      15 to 57 years) underwent second-look arthroscopic evaluations. The follow-up
      mean was 40.2 months (range, 24 to 70 months). We evaluated the results of manual
      knee laxity, anterior knee laxity measured by a Telos device (Telos, Marburg,
      Germany) at 130 N, Lysholm scores, and International Knee Documentation Committee
      evaluation form and performed evaluations of morphology by second-look
      arthroscopy. RESULTS: The side-to-side difference in anterior translation by use
      of the Telos device at 130 N was improved to 2 +/- 2 mm (postoperatively) from 6
      +/- 2.3 mm (preoperatively) in group A and to 1.02 +/- 1.26 mm from 4.93 +/- 1.73
      mm in group P. By second-look arthroscopy, the graft and preserved remnant of
      each case was considered to have acceptable synovial coverage and to be taut.
      CONCLUSIONS: The preserved ACL remnants possess acceptable morphology and the
      functions of anterior-posterior and rotational stability after surgery. Our
      procedure can be recommended for surgery on partial ACL tears. LEVEL OF EVIDENCE:
      Level IV, therapeutic case series.

PMID- 22381690
TI  - MicroRNA-182 regulates otocyst-derived cell differentiation and targets T-box1
      gene.
AB  - BACKGROUND: Recently, in vitro and in vivo models have identified that microRNAs
      (miRNAs), which are extensively expressed in the inner ear, play important roles
      in inner ear development and function. However, the function of miRNA in
      vertebrate tissue is not well understood. RESULTS: The current study used an in
      vitro model of embryonic mouse inner ear in a stem/progenitor cell culture to
      demonstrate that: 1) miR-182 is expressed during differentiation of inner ear
      stem/progenitor cell into a hair cell-like fate, 2) ectopic miR-182 promotes
      inner ear stem/progenitor cell differentiation into a hair cell-like fate, and 3)
      the function of miR-182 may be associated with its putative target Tbx1, a
      transcription factors that have been implicated in inner ear development and hair
      cell fate. CONCLUSIONS: Our findings suggest that miR-182 could regulate inner
      ear progenitor cell differentiation and that miRNAs are important regulators of
      hair cell differentiation, providing new targets for hair cell repair.

PMID- 22381691
TI  - A role for MRP8 in in stent restenosis in diabetes.
AB  - OBJECTIVE: The most common cause of death in diabetes mellitus is cardiovascular
      disease. Patients frequently undergo vascular intervention such as stenting. The
      occurrence of in stent restenosis (ISR) has been reduced by the use of drug
      eluting stents in non-diabetic patients but the incidence of restenosis and stent
      thrombosis remains higher in diabetic patients. We investigated the pathogenesis
      of in stent restenosis in an animal model of type 2 diabetes mellitus. METHODS
      AND RESULTS: Stents were placed in Zucker Fatty rat (ZFR) and wild type rat
      carotid arteries, and tissues were harvested 14 days post surgery for
      morphometric analysis. Unstented carotid arteries from both groups were harvested
      for microarray analysis. In vitro apoptosis, proliferation and migration assays
      were performed on rat and human aortic endothelial cells (EC). ZFRs developed an
      exaggerated intimal response to stent placement compared to wild type controls 14
      days post stent placement. MRP8 and MRP14 were up-regulated in unstented ZFR
      carotid arteries in comparison to controls. Expression of MRP8/14 was also
      elevated in EC exposed to high glucose conditions. EC function was impaired by
      high glucose concentrations, and this effect could be mimicked by MRP8 over
      expression. MRP8 knockdown by shRNA significantly restored EC function after
      exposure to high glucose concentrations. MRP8 expression in glucose exposed cells
      was also inhibited using pharmacological blockade of glucose-induced pathways.
      CONCLUSIONS: EC dysfunction caused by elevated glucose levels could be mimicked
      by MRP8/14 over-expression and reversed/prevented by MRP8 knockdown. Thus,
      MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8
      inhibition may be useful in improving outcome after stent placement in diabetes
      mellitus.

PMID- 22381692
TI  - Commentary: Gartner's 'third component': still an open question.

PMID- 22381693
TI  - Primary cutaneous cryptococcosis in a patient with CREST syndrome.

PMID- 22381694
TI  - Midline abdominal wall incisional hernia after aortic reconstructive surgery: a
      prospective study.
AB  - BACKGROUND AND PURPOSE: To evaluate rate of formation of midline abdominal wall
      incisional hernia (MAIH) after elective open repair of abdominal aortic aneurysm
      (AAA) and revascularization for aortoiliac occlusive disease (AOD). METHODS: AAA
      and AOD patients operated electively via a primary midline abdominal incision at
      our institution over a decade were entered in this prospective study. Patients
      who had already undergone midline laparotomy or had an MAIH after previous
      celiotomy were excluded. Patients were examined for MAIH 6-monthly for 2 years,
      then yearly. RESULTS: We included 1,065 patients who underwent aortic
      reconstructive surgery (412 with AAA and 653 with AOD). The follow-up (mean +/-
      standard deviation) was 6.4 +/- 3.8 years (range, 0.5-12.7). Wounds were closed
      with a suture length-to-wound length (SL:WL) ratio of at least 4:1 in 58% (239 of
      653) of AAA patients and 66% (431 of 653) of AOD patients (P = .01). There were
      124 (11.6%) MAIHs, with an incidence of 12.4% (51 of 412) in the AAA group and
      11.2% (73 of 653) in the AOD group (P = .62), and 3 (0.4%) wound infections (all
      among the AOD patients), none of which resulted in MAIH. At multivariate
      analysis, a SL:WL ratio of <4:1 was the only independent predictor of MAIH in AAA
      (P = .004) and AOD patients (P < .001). CONCLUSION: AAA and AOD patients had a
      similar incidence of MAIH, which seems related to the wound closure technique. A
      SL:WL ratio of at least 4:1 is recommended. Further clinical studies are required
      to determine possible technical and perioperative variables that may be modified
      to decrease the incidence of MAIH development after aortic reconstructive
      surgery.

PMID- 22381695
TI  - Pleiotrophic effects of natural products in ROS-induced carcinogenesis: the role
      of plant-derived natural products in oral cancer chemoprevention.
AB  - Cancer is a multistage process where each stage involves different molecular,
      biochemical and cellular events all of which, however, contribute to malignant
      transformation. Over the last years, substantial scientific evidence has promoted
      the hypothesis that ROS-induced cellular damage underlies key steps during
      development of the malignant phenotype including evasion of apoptosis, limitless
      proliferation, angiogenesis, tissue invasion and metastasis, etc. On the other
      hand, natural products hold great promise as anti-cancer compounds in preventing
      against carcinogenesis both in vitro and in vivo. Throughout this article, we aim
      to review the evidence as to how some of these natural products exert their
      chemopreventive effects in human carcinogenesis. For this reason, we have placed
      particular emphasis on oral cancer where significant efforts have been made in
      alternative therapeutic strategies such as the use of plant-derived natural
      products. This is of paramount importance given the disease's high morbidity and
      mortality rates across the world and specifically in the geographic regions of
      India and South-East Asia where its incidence is increasing.

PMID- 22381696
TI  - RNA interference-mediated silencing of NANOG reduces cell proliferation and
      induces G0/G1 cell cycle arrest in breast cancer cells.
AB  - Since the processes of normal embryogenesis and neoplasia share many of similar
      pathways, tumor development has been interpreted as an abnormal form of
      organogenesis. NANOG is a homeodomain-containing transcription factor that
      functions to maintain self-renewal and proliferation of embryonic stem cells
      (ESCs). Aberrant expression of NANOG has been observed in many types of human
      malignancies. However, its potential implication in tumorigenesis has not been
      fully clarified. In this study, we have employed small interference RNA (RNAi)
      technology to silence endogenous NANOG expression in breast cancer cells and
      successfully selected three independent clones with stably inhibited NANOG
      expression of MCF-7 cells. Functional analysis revealed that down-regulation of
      NANOG reduced cell proliferation, colony formation and migration ability of MCF-7
      cells. Consistently, proliferation of breast cancer MDA-MB-231 cells was also
      significantly inhibited after the knockdown of NANOG expression. Interestingly,
      we found that the expression levels of cyclinD1 and c-myc were markedly down
      regulated and the cell cycle were blocked at the G0/G1 phases after the knockdown
      of NANOG, while the expression of cyclinE and signal transducers and activators
      of transcription3 (STAT3) remained unaffected. In addition, the expression of
      NANOG and cyclinD1 can be rescued after the transfection of pcDNA3.1 (-)-NANOG
      expression vector into the three clones. Finally, our chromatin
      immunoprecipitation (ChIP) experiment showed that NANOG protein can bind to the
      promoter region of cyclinD1 and regulate cells cycle. Taken together, our
      findings may not only establish a molecular basis for the role of NANOG in
      modulating cell cycle progression of breast cancer cells but also suggest a
      potential target for the treatment of at least some subtypes of breast cancer.

PMID- 22381697
TI  - Structure and biosynthetic assembly of cupriachelin, a photoreactive siderophore
      from the bioplastic producer Cupriavidus necator H16.
AB  - The bacterium  Cupriavidus necator  H16 produces a family of linear lipopeptides
      when grown under low iron conditions. The structural composition of these
      molecules, exemplified by the main metabolite cupriachelin, is reminiscent of
      siderophores that are excreted by marine bacteria. Comparable to marine
      siderophores, the ferric form of cupriachelin exhibits photoreactive properties.
      Exposure to UV light induces an oxidation of its peptidic backbone and a
      concomitant reduction of the coordinated Fe(III). Here, we report the genomics
      inspired isolation and structural characterization of cupriachelin as well as its
      encoding gene cluster, which was identified by insertional mutagenesis. Based
      upon the functional characterization of adenylation domain specificity, a model
      for cupriachelin biosynthesis is proposed.

PMID- 22381698
TI  - Midazolam is associated with delay in recovery and agitation after ambulatory
      general anesthesia for dental treatment in patients with disabilities: a
      retrospective cohort study.
AB  - PURPOSE: Some patients with intellectual disabilities (IDs) who undergo total
      intravenous anesthesia (TIVA) have complications associated with the anesthesia
      such as prolonged recovery. The purposes of this study were to estimate the
      frequency of TIVA complications among patients with IDs and to identify factors
      associated with TIVA complications. MATERIALS AND METHODS: This study was
      designed as a retrospective cohort study. Study samples were selected from the
      clinical records of patients with IDs who underwent ambulatory general anesthesia
      in a special dental clinic at the Okayama University Hospital, Okayama, Japan.
      Predictor variables were patient background, anesthesia-related variables, and
      dental treatment. Outcome variables were delayed recovery and the complication of
      agitation. Factors affecting delayed recovery and complications were examined
      with multivariable analysis. RESULTS: We enrolled 106 cases (81 male and 25
      female patients) in this study. The mean age was 23.9 years. Serious
      complications were not observed in any cases. The amount of intravenous midazolam
      was an independent determinant of delayed recovery. Oral midazolam contributed to
      delayed recovery, although it is very useful for induction in patients with a
      high level of fear. Oral midazolam and a younger age were independent predictors
      of agitation. CONCLUSIONS: Intravenous midazolam may not have an advantage in
      ambulatory general anesthesia. Oral midazolam contributes to delayed recovery and
      is an independent predictor of agitation.

PMID- 22381699
TI  - Development of superior bone scintigraphic agent from a series of (99m)Tc-labeled
      zoledronic acid derivatives.
AB  - Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane
      1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1
      diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide
      technetium-99m in a high labeling yield. In vitro stabilities of these
      radiolabeled complexes were measured by the radio-HPLC analysis as a function of
      time, which showed excellent stability with the radiochemical purity of over 95%
      at 6h post preparation. Their in vivo biological performances were evaluated and
      compared with those of (99m)Tc-ZL and (99m)Tc-MDP (methylenediphosphonic acid).
      The biodistribution in mice and scintigraphic images of the rabbit showed that
      the tracer agent (99m)Tc-IPeDP had highly selective uptake in the skeletal system
      and rapid clearance from the blood and soft tissues and an excellent
      scintigraphic image can be obtained in a shorter time post injection with clear
      visualization of the skeleton and low soft tissue activity. These preclinical
      studies suggest that (99m)Tc-IPeDP would be a novel superior bone scintigraphic
      agent.

PMID- 22381700
TI  - Review of doped silica glass optical fibre: their TL properties and potential
      applications in radiation therapy dosimetry.
AB  - Review is made of dosimetric studies of Ge-doped SiO(2) telecommunication fibre
      as a 1-D thermoluminescence (TL) system for therapeutic applications. To-date,
      the response of these fibres has been investigated for UV sources, superficial X
      ray beam therapy facilities, a synchrotron microbeam facility, electron linear
      accelerators, protons, neutrons and alpha particles, covering the energy range
      from a few eV to several MeV. Dosimetric characteristics include,
      reproducibility, fading, dose response, reciprocity between TL yield and dose
      rate and energy dependence. The fibres produce a flat response to fixed photon
      and electron doses to within better than 3% of the mean TL distribution.
      Irradiated Ge-doped SiO(2) optical fibres show limited signal fading, with an
      average loss of TL signal of ~0.4% per day. In terms of dose response, Ge-doped
      SiO(2) optical fibres have been shown to provide linearity to x and electron
      doses, from a fraction of 1 Gy up to 2 kGy. The dosimeters have also been used in
      measuring photoelectron generation from iodinated contrast media; TL yields being
      some 60% greater in the presence of iodine than in its absence. The review is
      accompanied by previously unpublished data.

PMID- 22381701
TI  - Thermoluminescence property of LiMgF3 erbium activated phosphor.
AB  - The perovskite-like LiMgF(3):ErF(3) pellets were obtained from the melt formed by
      LiF and MgF(2) mixed salts in the stoichiometric ratio. The perovskite material
      was doped with 1, 2 and 4 mol% of ErF(3) impurity. The pellets samples were
      (60)Co gamma irradiated and their thermoluminescence (TL) properties were
      analyzed, i.e., dose-response, fading at RT and under UV irradiation, TL signal
      reproducibility, and kinetic parameters. The intensity of the TL response against
      irradiation dose was increased remarkably by the high concentration of impurity,
      and a linear dose-response was observed in the range of 1-10 Gy. The fading
      observed at RT was about 10-30% after 24h from irradiation. All samples were
      exposed from 1 to 200 Gy gamma dose range. The TL glow peaks were found around
      367-376, 438-447, 509-521, and 594-611 K, when the doped samples were 1, 2 and 4
      mol% of the erbium impurity concentration. The thermoluminescence kinetics
      parameters of the glow curves have been analyzed using the Computerized Glow
      Curve Deconvolution (CGCD) method.

PMID- 22381702
TI  - Phase II trial of syncopated thalidomide, lenalidomide, and weekly dexamethasone
      in patients with newly diagnosed multiple myeloma.
AB  - Thalidomide and lenalidomide, in combination with dexamethasone, provide response
      rates ranging from 63%-79% after 4 cycles of therapy. Because of toxicities such
      as neuropathy and myelosuppression for thalidomide and lenalidomide,
      respectively, dose escalation has not been pursued. We evaluated a syncopated
      regimen of alternating weeks of thalidomide and lenalidomide to determine if a
      modified schedule allows for fewer dose reductions and, subsequently, superior
      efficacy. Although well tolerated, this phase II trial did not show superior
      efficacy compared with conventional dosing and scheduling of these agents.
      INTRODUCTION: Over the past decade, the novel agents thalidomide, lenalidomide,
      and bortezomib have emerged as effective treatment in patients with multiple
      myeloma (MM). Initially used in the relapse setting, these agents have been
      incorporated into frontline treatment algorithms. They have been combined in
      doublets with corticosteroids, in triplets with alkylators, or with each other.
      Because thalidomide and lenalidomide have different clinical activity and
      toxicity profiles, we designed a trial to evaluate a syncopated schedule of
      thalidomide and lenalidomide with weekly dexamethasone in patients with newly
      diagnosed MM to determine response and toxicity. PATIENTS AND METHODS: Twenty-two
      patients with newly diagnosed MM were treated with syncopated thalidomide (200 mg
      on days 1-7 and 15-21), lenalidomide (25 mg on days 8-14 and 22-28 for the first
      cycle and 50 mg on the same schedule for subsequent cycles) with weekly
      dexamethasone (40 mg). Each cycle lasted 28 days. MM parameters were assessed at
      the end of each cycle. It was intended that the patients proceed to stem cell
      mobilization and autologous transplantation after 4 cycles of therapy. RESULTS:
      The median number of cycles administered was 3.5. The overall response was 68%.
      The regimen was well tolerated by the majority of the patients; only patient
      discontinued treatment because of toxicity. CONCLUSION: We conclude that a
      syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone was
      tolerated well, with no unexpected toxicities. However the response rate, even
      using lenalidomide at 50 mg, was not superior to standard dosing of thalidomide
      or lenalidomide plus dexamethasone.

PMID- 22381703
TI  - Bisphenol A and infant neonatal neurobehavior.

PMID- 22381704
TI  - Effects of addition of different vegetable oils to lactating dairy ewes' diet on
      meat quality characteristics of suckling lambs reared on the ewes' milk.
AB  - The effect of different vegetable oils used in the diet of lactating ewes on the
      meat quality of their suckling lambs has been evaluated. Lambs (males and
      females) were slaughtered at 11 kg. Fortyeight lactating Churra ewes (prolificacy
      1.5) and their suckling lambs were assigned to four treatments according to the
      oil added (3% on weight basis) to the ewes' daily ration: palm oil as control
      (CON); olive oil (OLI); soybean oil (SOY); and linseed oil (LIN). Analyses of pH,
      colour, thiobarbituric acid reactive substances (TBARS), tocopherol levels,
      volatile compounds and a sensory evaluation were carried out on suckling lambs'
      meat. Results showed no substantial effect on pH, colour, TBARS and tocopherol
      levels. Volatiles typically derived from lipid oxidation were higher in SOY
      group. However, panellists were only able to correctly identify samples from LIN
      group. Furthermore, the meat from LIN group showed lower scores towards odour and
      flavour quality and overall liking than that from the rest of treatments.

PMID- 22381705
TI  - Atrial fibrillation increases the risk of cognitive decline and need for long
      term care.

PMID- 22381706
TI  - Radiotherapy research trials in the UK: secrets of success.

PMID- 22381707
TI  - Accuracy of a point-of-care ELISA test kit for predicting the presence of
      protective canine parvovirus and canine distemper virus antibody concentrations
      in dogs.
AB  - Canine parvovirus (CPV) and canine distemper virus (CDV) are highly infectious
      and often fatal diseases with worldwide distributions, and are important
      population management considerations in animal shelters. A point-of-care ELISA
      test kit is available to detect serum antibodies to CPV and CDV, and
      presumptively to predict protective status. The aim of this study was to
      determine the diagnostic accuracy of the test compared to CPV hemagglutination
      inhibition titers and CDV serum neutralization titers determined by a reference
      laboratory, using sera collected from dogs housed at animal shelters. The ELISA
      test was used under both field and laboratory conditions and duplicate specimens
      were processed using an extra wash step. The test kit yielded accurate results
      (CPV: sensitivity 92.3%, specificity 93.5%; CDV: sensitivity 75.7%, specificity
      91.8%) under field conditions. CDV sensitivity was improved by performing the
      test under laboratory conditions and using an optical density (OD) meter
      (laboratory performed 94.0%; OD 88.1%). Point-of-care ELISA testing for serum CPV
      and CDV antibody titers was demonstrated to be a useful tool for determining
      antibody status when making decisions regarding the need for CPV and/or CDV
      vaccination and also in animal shelters for population management.

PMID- 22381708
TI  - Post-anesthetic cortical blindness in cats: twenty cases.
AB  - The medical records of 20 cats with post-anesthetic cortical blindness were
      reviewed. Information collected included signalment and health status, reason for
      anesthesia, anesthetic protocols and adverse events, post-anesthetic visual and
      neurological abnormalities, clinical outcome, and risk factors. The vascular
      anatomy of the cat brain was reviewed by cadaver dissections. Thirteen cats were
      anaesthetised for dentistry, four for endoscopy, two for neutering procedures and
      one for urethral obstruction. A mouth gag was used in 16/20 cats. Three cats had
      had cardiac arrest, whereas in the remaining 17 cases, no specific cause of
      blindness was identified. Seventeen cats (85%) had neurological deficits in
      addition to blindness. Fourteen of 20 cats (70%) had documented recovery of
      vision, whereas four (20%) remained blind. Two cats (10%) were lost to follow up
      while still blind. Ten of 17 cats (59%) with neurological deficits had full
      recovery from neurological disease, two (12%) had mild persistent deficits and
      one (6%) was euthanased as it failed to recover. Four cats (23%) without
      documented resolution of neurological signs were lost to follow up. Mouth gags
      were identified as a potential risk factor for cerebral ischemia and blindness in
      cats.

PMID- 22381709
TI  - [Dental trauma].

PMID- 22381710
TI  - Evaluation of health care costs and utilization patterns for patients with gout.
AB  - BACKGROUND: The prevalence of gout has been increasing. Serum uric acid (sUA)
      levels >=6 mg/dL have been associated with high morbidity and increased health
      care utilization. OBJECTIVE: To assess the costs and patterns of health care
      resource utilization for patients with gout, categorized into 3 cohorts based on
      sUA levels. METHODS: We retrospectively analyzed laboratory, pharmacy, and
      medical service claims data (January 2005 to June 2010) for patients >=18 years
      old. Inclusion criteria were at least 2 sUA levels and at least 1 primary gout
      diagnosis (International Classification of Disease-9th revision code 274.xx),
      and/or at least 1 prescription for gout-specific medications. Outcomes including
      costs, health care resource utilization, and medication adherence and persistence
      were assessed for the 1-year postindex period and summarized for the 3 cohorts
      based on sUA levels: <6 mg/dL, 6 to 8.99 mg/dL, and >=9 mg/dL. Costs were
      adjusted based on preindex utilization and baseline characteristics. RESULTS:
      Three hundred fifty-two patients met the inclusion criteria: cohort 1 (sUA <6
      mg/dL), n = 38, mean age 59 years; cohort 2 (sUA 6-8.99 mg/dL), n = 231, mean age
      61 years; and cohort 3 (sUA >=9 mg/dL), n = 83, mean age 62 years. Mean adjusted
      gout-related health care costs were $332, $353, and $663, respectively (P <0.05);
      mean adjusted all-cause health care costs were $11,365, $11,551, and $14,474,
      respectively, for the 3 cohorts (P <0.05). sUA levels were positively associated
      with the percent of patients who had at least 1 hospitalization and the mean
      number of hospitalizations and emergency department visits (P < 0.05).
      Significantly more patients with sUA <6 mg/dL achieved adherence rates of >=80%
      and had a longer mean duration of continuous treatment compared with patients
      with sUA between 6 and 8.99 mg/dL or >=9.0 mg/dL (P <0.05). CONCLUSIONS: Patients
      with high levels of sUA had higher gout-related and all-cause health care costs,
      more all-cause hospitalizations, and emergency department visits, but they also
      exhibited poorer adherence and persistence.

PMID- 22381712
TI  - Adherence to oral antidiabetic medications in the pediatric population with type
      2 diabetes: a retrospective database analysis.
AB  - BACKGROUND: Little has been done in assessing adherence to oral antidiabetic
      (OAD) medications in the pediatric population presenting with type 2 diabetes.
      This study provided information on adherence rates in the Texas Medicaid
      pediatric population with type 2 diabetes, which is rare in the literature. The
      knowledge of adherence rates in the pediatric population with type 2 diabetes
      might help improve the care given to pediatric patients with type 2 diabetes.
      OBJECTIVE: To describe OAD medication use, and assess trends in medication
      adherence and persistence among Texas pediatric Medicaid patients. METHODS: Texas
      Medicaid prescription claims data of patients between 10 and 18 years of age,
      with at least 2 prescriptions of the same OAD medication from January 1, 2006 to
      December 31, 2009, were analyzed. Adherence was assessed using the medication
      possession ratio (MPR) as a proxy. RESULTS: A total of 3109 patients met the
      study's inclusion criteria. The mean (SD) age of the 3109 eligible patients was
      14.2 (2.3) years; 60% were Hispanics, 14% were blacks, 13% were whites, and
      another 13% were other minority races; 67% of the population were females; and
      91% were on metformin of the 6 OAD medications included in the study The overall
      mean (SD) MPR for patients was 44.69% (27.06%). Adherence differed by gender (P <
      0.0001), race (P < 0.0001), and age category (P < 0.0001). Males had higher mean
      (SD) MPR (47.47% [27.42%]) compared with females (43.29% [26.78%]). Mean MPR for
      whites (50.04% [29.65%]) was significantly higher compared with blacks (44.24%
      [26.16%]) and Hispanics (42.50% [26.10%]). Patients <=12 years of age had
      significantly higher mean MPR (48.82% [27.37%]) compared with those in older age
      categories. Logistic regression analysis suggested that age was significantly
      related (odds ratio [OR] = 0.91; 95% CI, 0.87-0.95) to being adherent (MPR
      >=80%). Males were 25% (OR = 1.25; 95% CI, 1.02-1.53; P = 0.034) more likely to
      be adherent (MPR >=80%) compared with females, and whites were twice as likely to
      be adherent (MPR >=80%) compared with Hispanics (OR = 2.02; 95% CI, 1.54-2.66; P
      = 0.0012). Overall, mean (SD) days to nonpersistence was 108 (86) days.
      Persistence was significantly and negatively associated with age (P < 0.0001).
      White race was significantly related to longer persistence. CONCLUSION: Adherence
      and persistence to OAD medications in the selected Texas Medicaid pediatric
      population between 10 and 18 years was generally suboptimal, especially in
      adolescents.

PMID- 22381711
TI  - Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker,
      compared with losartan (50/100 mg): a 12-week, phase III, multicenter,
      prospective, randomized, double-blind, parallel-group, dose escalation clinical
      trial with an optional 12-week extension phase in adult Korean patients with mild
      to-moderate hypertension.
AB  - BACKGROUND: Angiotensin receptor blockers (ARBs) is an effective and well
      tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB
      that has not been compared with other ARBs with regard to its efficacy and
      tolerability. OBJECTIVE: The goal of this study was to determine the
      noninferiority of fimasartan to losartan with regard to its efficacy and
      tolerability in adult Korean patients with mild-to-moderate hypertension.
      METHODS: This was a randomized, multicenter, double-blind, parallel group, dose
      escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70
      years with mild-to-moderate hypertension were randomized to receive either
      fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration.
      Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The
      primary end point was noninferiority of improvement in mean siDBP from baseline
      to week 12 for fimasartan compared with losartan. The incidence and severity of
      adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess
      their tolerability. In addition, some patients whose blood pressure reached goal
      levels participated in a 24-week extension study for additional assessment of
      tolerability and efficacy. RESULTS: Five hundred six patients were randomly
      allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no
      significant difference in baseline demographic characteristics between the 2
      treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean
      weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58
      [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was
      significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the
      fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The
      between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the
      2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority
      margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the
      fimasartan and losartan groups, respectively (chi(2) test, P = 0.3181). The
      efficacy of fimasartan was maintained over 24 weeks, and its tolerability was
      comparable with losartan in the extension study. CONCLUSIONS: In this study with
      eligible adult Korean patients who had mild-to-moderate hypertension, the
      reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was
      noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group
      differences in siDBP were significant in favor of fimasartan, suggesting
      superiority to losartan. There was no statistically significant difference in
      tolerability between the groups. This efficacy and tolerability were maintained
      throughout the additional 12-week extension study.

PMID- 22381713
TI  - The influence of sparse data sampling on population pharmacokinetics: a post hoc
      analysis of a pharmacokinetic study of morphine in healthy volunteers.
AB  - BACKGROUND: Intensive sampling of patients for drugs with complex pharmacokinetic
      profiles is difficult to perform in the clinic or hospitalized patient setting.
      We seek to address whether sparse sampling can obtain pharmacokinetic parameter
      values similar to those with traditional modeling from a post hoc analysis of 2
      previous clinical trials. OBJECTIVE: This study investigated whether population
      guided, sparse-sampling pharmacokinetic analysis of morphine in 14 healthy
      volunteers allowed for optimal characterization of concentration-time profiles
      for a validation population of 5 young male patients receiving morphine. METHODS:
      Data were analyzed using nonparametric adaptive grid (NPAG) population modeling
      to investigate optimal compartmental structure and the influence of sparse
      sampling (ie, 9 versus 3 samples per subject) on parameter identification. These
      results were compared with traditional standard 2-stage (STS) pharmacokinetic
      modeling. The coefficients of determination (R(2)), mean error (ME), and root
      mean-square error were used to assess the predictive performance of the various
      sampling models against a validation population. RESULTS: Seventy-nine percent of
      the healthy volunteers were male, with a mean age of 36 (17) years and a mean
      weight of 68 (10) kg. NPAG modeling identified that intravenous morphine was best
      represented by a 3-compartment pharmacokinetic profile and that sparse sampling
      with a least 3 blood samples per subject resulted in virtually identical measures
      of central tendency as the more intensively sampled dataset. A validation cohort
      of 5 male patients undergoing elective surgery had a mean age of 26 (4) years and
      a mean weight of 80 (13) kg. Using mean parameter estimates generated from sparse
      sampling and the 3-compartment model structure, simulated profiles were compared
      against measured concentrations in this validation cohort. Sparse sampling using
      NPAG achieved similar values of predictive performance as mean parameter values
      from the more intensively sampled, with an ME of -1.0 ng/mL and precision of 26.2
      ng/mL compared with 0.76 ng/mL and 25.8 ng/mL, respectively. Traditional (STS)
      modeling techniques resulted in the greatest degree of underprediction within the
      validation group (ME = 4.43 versus 0.76 ng/mL, STS and NPAG-9, respectively; P <
      0.0001). CONCLUSIONS: This post hoc analysis suggests that intensive sampling for
      discerning complex, 3-compartment pharmacokinetic models, such as morphine, may
      not be necessary. Sparse sampling achieved accurate model structure recognition
      and parameter identification for predicting concentrations of very complex drug
      dosage regimens.

PMID- 22381714
TI  - Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose
      study of the oral gamma-secretase inhibitor BMS-708163 (Avagacestat):
      tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers.
AB  - BACKGROUND: gamma-Secretase inhibitors (GSIs) are being investigated for their
      potential to modify the progression of Alzheimer disease based on their ability
      to regulate amyloid-beta (Abeta) accumulation. BMS-708163 (avagacestat) is an
      oral GSI designed for selective inhibition of Abeta synthesis currently in
      development for the treatment of mild to moderate and predementia AD. In addition
      to the desired effect on Abeta synthesis, GSIs affect Notch processing, which is
      thought to mediate some toxic adverse effects reported with this drug class.
      Avagacestat produced up to 190-fold greater selectivity for Abeta synthesis than
      Notch processing in preclinical studies and may therefore produce less toxic
      adverse events than other less selective compounds. Presented here are the
      results of the first in-human study for this new GSI compound. OBJECTIVE: The
      goal of this study was to assess the tolerability profile, pharmacokinetic
      properties, and effects on pharmacodynamic markers (Abeta, trefoil factor family
      3 protein, dual specificity phosphatase 6, and hairy and enhancer of split-1) of
      single, oral doses of avagacestat in healthy, young, male volunteers. METHODS:
      This was a multicenter, randomized, double-blind, placebo-controlled, single
      ascending dose study in 8 healthy young men (age, 18-45 years) per dosing panel.
      Each study participant was randomized to receive a single dose of placebo (n = 2)
      or avagacestat (n = 6 for each dose) as an oral solution in 1 of 9 sequential
      dose panels (0.3, 1.5, 5, 15, 50, 100, 200, 400, and 800 mg). For determination
      of avagacestat, blood samples were obtained before dosing and for up to 144 hours
      after dosing. For participants in the 800-mg avagacestat dose panel, additional
      samples were obtained at 216, 312, and 648 hours. For 40-amino acid isoform of
      Abeta (Abeta(1-40)) assessment, plasma samples were collected before avagacestat
      administration and up to 72 hours after dosing. RESULTS: Avagacestat
      concentrations peaked quickly after oral administration and then had a biphasic
      decrease in concentrations with a prolonged terminal phase. Exposures were
      proportional with doses up to 200 mg. Avagacestat was well tolerated at single
      oral doses up to 800 mg, with a biphasic effect on plasma Abeta(1-40). Adverse
      events were predominately mild to moderate in severity with no evidence of dose
      dependence up to 200 mg. CONCLUSIONS: Results from this single-ascending dose
      study suggest that avagacestat was tolerated at a single-dose range of 0.3 to 800
      mg and suitable for further clinical development.

PMID- 22381715
TI  - Morphine use in hospitalized children in the United States: a descriptive
      analysis of data from pediatric hospitalizations in 2008.
AB  - BACKGROUND: Morphine is among the top 10 medications given to children in the
      inpatient setting. It is not labeled for any pediatric indication, making it one
      of the drugs most widely used off-label in pediatrics. OBJECTIVES: The aims of
      this study were to describe the epidemiology of morphine use in pediatric
      inpatients in the United States and to describe the characteristics of patients
      and hospitals in hospitalizations with morphine use. METHODS: Deidentified data
      from the Premier Perspective Database (2008) were analyzed. Morphine use was
      defined as any morphine administration during the hospital stay and estimated by
      patient age in years, sex, race, and type of insurance; and hospital bedsize,
      teaching status, setting (urban or rural), and geographic location. Proportions
      (95% CI) were calculated for the entire population and for individual strata. The
      estimate was applied to national data to calculate the number of pediatric
      hospitalizations with morphine use in the United States in 2008. Logistic mixed
      effects modeling was used to calculate the probability of morphine use by
      hospital after controlling for hospital and patient effects. RESULTS: The
      database contained records from 877,201 pediatric hospitalizations and 423
      hospitals in the United States. Morphine was administered in 54,613 of pediatric
      hospitalizations (6.2%). Use was higher in boys than girls (6.4% and 6.1%,
      respectively) and in blacks compared with whites or other racial groups (7.5%,
      6.7%, and 5.0%). Use increased from 1.6% in children aged <2 years to 27.4% in
      those aged 12 to 17 years. Based on these data, morphine may have been
      administered in 476,205 pediatric hospitalizations in the United States in 2008.
      The 2 diagnoses most frequently associated with morphine use were appendicitis
      (14.4%) and fracture (11.1%). On logistic mixed-effects modeling for patients
      with appendicitis and for patients with fractures, there was hospital variation
      in morphine use after controlling for variables in the model. CONCLUSIONS: Based
      on the data from this analysis, morphine was used in hospitalized children in all
      age groups, despite the lack of pediatric labeling. Common conditions such as
      appendicitis and fracture were leading diagnoses associated with morphine use.

PMID- 22381716
TI  - Cost containment interventions introduced on the community drugs schemes in
      Ireland-evaluation of expenditure trends using a national prescription claims
      database.
AB  - BACKGROUND: The majority of pharmaceutical expenditure in Ireland occurs in the
      community for services provided by general practitioners and pharmacists. In the
      current national and international economic climate, it is anticipated that
      demand on these services will continue to grow. OBJECTIVE: The aim of this
      article was to examine trends in expenditure of pharmaceuticals on the Community
      Drugs Schemes from 2005 to 2010, and to examine the impact of cost-containment
      interventions on expenditures that were introduced at this time and affected the
      pricing mechanism for pharmaceuticals in Ireland. METHODS: Prescription data were
      analyzed using an Irish national prescription claims database according to drug
      category, that is, generic, patent, and off patent for the 2 largest schemes; the
      publicly funded General Medical Services (GMS) Scheme and copayment Drugs Payment
      (DP) Scheme. Segmented regression analysis of interrupted time series was used to
      analyze the effects of the interventions on expenditure. RESULTS: An increase in
      expenditure was noted across all schemes up to 2009 and declined thereafter to
      the end of the study period (October 2010). Significant reductions in expenditure
      were noted after introduction of a 20% price cut to patent-expired products (off
      patents) (P < 0.001). In July 2009, pharmacy and wholesale margins were reduced,
      resulting in significant reductions in expenditure for patented (GMS Scheme: P <
      0.05 and DP Scheme: P < 0.001) and generic (DP Scheme only: P < 0.01) products.
      Significant reductions in expenditure were noted for off-patent products on the
      GMS Scheme at this time (P < 0.01). No significant reductions in expenditure were
      noted for off patents after a 15% price reduction in January 2009. An additional
      40% price reduction in February 2010 resulted in significant reductions in
      expenditure for off-patent products on both the GMS (P < 0.01) and DP Scheme (P <
      0.05). CONCLUSIONS: Results from this study, based on a section of the total
      population of Ireland during a 6-year period, indicate that reductions in the
      wholesale margin and pharmacy markup had the largest impact on reducing
      pharmaceutical expenditure during the study period.

PMID- 22381717
TI  - [The role of temperament and emotional awareness in risk taking in adolescents].
AB  - INTRODUCTION: Risk-taking behaviors among adolescents are now considered as a
      real public health issue. To investigate for potential vulnerability factors,
      adolescent risk-taking behavior can be analyzed from several different
      perspectives, based on biological, social or psychological variables. Risk-taking
      theories based on temperamental dimensions examine individual differences in
      propensity for engaging in such behaviors, whereas others focused on emotional
      processing disorder such as alexithymia or anhedonia with diverse conclusions.
      The aim of this study was to investigate the relationship between risk taking and
      two levels of psychological functioning: personality with reference to
      Cloninger's model of personality, and emotion with reference to Lane and
      Schwartz's level of emotional awareness theory. METHOD: The sample consisted in
      488 adolescents (m(age)=14.93, SD=1.44) with 257 boys (m(age)=15, SD=1.51) and
      231 girls (m(age)=14.52, SD=1.23) who completed a set of three inventories: the
      Youth Risk Behavior Surveillance Scale (YRBSS), the Tridimensional Personality
      Questionnaire, and the Level of Emotional Awareness Scale. Risk-taking behaviors
      were also assessed indirectly with regards to teachers or school educators'
      evaluation. RESULTS: Moderate to weak significant correlations were found between
      temperament dimensions and risk-taking, and between level of emotional awareness
      and risk-taking. A positive moderate correlation was observed between novelty and
      risk-taking, whereas a negative weak correlation was observed between harm
      avoidance and risk-taking. Level of emotional awareness shows moderate negative
      correlations with risk-taking, as the two self and others dimensions. Finally, a
      model including the four temperament and the two emotional awareness dimensions
      was tested with risk-taking as the outcome variable. It accounted for 33% of the
      total variance (R(2)=0.33; F=30.78, p<0.0001), with novelty seeking (p<0.0001),
      self (p<0.0001) and others (p=0.0001), and level of emotional awareness as
      significant criteria. DISCUSSION: As hypothesized, temperamental dispositions of
      novelty seeking and harm avoidance, associated with weak emotional awareness,
      were associated with risk-taking. They may be considered as vulnerability factors
      for adolescents to engage in risk-taking behaviors. Several propositions may
      explain our results. First, risk-taking might be considered as an attempt to
      struggle against a sensation of emptiness due to a lack of emotion. Second, it
      may tend to replace emotion by sensations, which could be more controlled. Third,
      it could be an attempt - without success - to construct the complexity of
      subjective emotional experience.

PMID- 22381718
TI  - [Homosexual parenthood and child development: present data].
AB  - INTRODUCTION: The aim of this article is to provide an overview of existing
      studies on gay and lesbian parenthood and child development. Although 200,000 to
      300,000 children could be concerned in 2010 in France, there is a lack of
      research on this issue in our country. BACKGROUND: Research among children raised
      by homosexual parents involves methodological issues, such as defining homosexual
      families, sampling cases and controls, and choosing structured or semi-structured
      evaluations. The fact that homosexual marriage, adoption and insemination are not
      presently legal in France could explain that only one study has been conducted in
      France in 2000 among 58 children raided by homosexual parents. This study
      concluded that these children did not show an increased rate of behavior or
      anxiety disorders. LITERATURE FINDINGS: Concerns about lesbian parenting have
      focused on the absence of a father, the homosexual orientation of the mother, and
      their negative consequences on the development of the children. Research on
      parenting and child rearing has repeatedly compared lesbian and heterosexual
      families, and in the last 30 years a growing body of studies on lesbian parents
      and the development of their children has been published. Studies about child
      development, sexual orientation, gender identity, gender role behavior,
      emotional/behavioral development, social relationships and cognitive functioning
      showed no difference between children of lesbian mothers and those of
      heterosexual parents. Likewise, parental functioning, the mothers' psychological
      health and maternal skills were not significantly different among lesbian mothers
      than among heterosexual mothers. In studies concerning gay fathers, findings
      generally indicate no differences in sexual orientation, socialization, or
      psychological outcomes in children of gay fathers compared to children of
      heterosexual fathers. However, the first study on the adult attachment style
      dimensions of adult women who had gay or bisexual fathers suggested that they
      were significantly less comfortable with closeness and intimacy, less able to
      trust and depend on others, and experienced more anxiety in relationships than
      women with heterosexual fathers. This survey has not been argued among lesbian
      families or coparentality. DISCUSSION: Variables related to family processes,
      such as relationship quality, are currently considered more important predictors
      of children's adjustment in homosexual families than sexual orientation. The
      major part of the literature focused on children aged four to 16 and the small
      sample size (often less than 30 children) limit the validity of these data.
      However, very little is known about psychological characteristics or well-being
      of adult children of lesbian and gay parents, and research should be pursued in
      the future. Social relationships of children raised by homosexual families, their
      experience of difference, and the discrimination are also likely to vary with the
      culture of each country and was not evaluated to our knowledge to date in cross
      cultural studies using standardized questionnaires. CONCLUSION: Our practice must
      find new reference marks to understand the stakes and the difficulties of these
      configurations for a better empathy with the child and his/her family.

PMID- 22381719
TI  - [Anxiety in children and adolescents with pervasive developmental disorder
      without mental retardation: review of literature].
AB  - OBJECTIVE: Anxiety is highly prevalent in Pervasive Developmental Disorder (PDD)
      without mental retardation but is too often misdiagnosed. The authors suggest a
      critical review of current data of the PDD without mental retardation in children
      and adolescents, in order to summarize research published in this field. After
      describing specific features, this article tackles the issue of prevalence of
      anxiety among this population, then deals with present-time assessment and
      treatments of comorbid anxiety. METHODS: This review was based on a systematic
      search of the main online databases (Science Direct, PsychInfo, Medline and
      Pubmed) in order to compile surveys published on Asperger syndrome and high
      functioning autism-related anxiety among children and adolescents. This study
      focuses on papers published between 1995 and 2010, using strict diagnostic
      criteria for anxiety and PDD, and a controlled group, with the exception of
      pharmacological studies because none are controlled. We found seven studies
      assessing the prevalence of anxiety among children and adolescents with PDD, four
      assessment tools and 12 treatments. RESULTS: Anxiety disorders were shown in 42%
      of children and adolescents with PDD without mental retardation. This disorder is
      related to age and level of cognitive functioning and is likely to affect PDD
      without mental retardation as children and adolescents with anxiety disorder
      without PDD. This review highlights a major problem: assessment of anxiety in PDD
      without mental retardation. Actually, only two PDD adapted instruments have been
      found: the Autism Co-Morbidity Interview Present and Lifetime Version (ACI-PI)
      and the Stress Survey Schedule (SSS) for persons with autism. Such tools being
      methodologically limited, the diagnosis of anxiety disorder is all the more
      difficult to establish. Consequently, considering suitable treatment is not
      always proposed. Recent surveys show how profitable pharmacological treatment and
      behavioral intervention like Cognitive-Behavior Therapy (CBT) or psychosocial
      treatments are. However, important methodological limitations are evoked: there
      is no control study assessing the efficiency of a pharmacological treatment in
      Asperger syndrome and high-functioning autism. Besides, the research on how
      profitable cognitive and behavioral treatment is, gives heterogeneous results.
      Finally, social skills' training does not treat anxiety disorder directly, but
      skills abilities that are the most important disabilities in PDD without mental
      retardation. Therefore, authors advocate adapting treatment in order to treat
      anxiety disorder. CONCLUSION: The research revealed an important need to create
      new assessment instruments suitable to PDD without mental retardation in order to
      facilitate the co-morbidity diagnosis. This survey also underlines the necessity
      to develop controlled research testing the efficiency of such treatments as
      pharmacological ones, cognitive and behavioral therapies as well as social skills
      training.

PMID- 22381720
TI  - [Can one talk of benzodiazepine "drunkenness"? About acute benzodiazepine
      intoxication, without suicidal or mortiferous tendencies].
AB  - BACKGROUNDS: When we refer to "drunkenness", more often than not, we think of
      alcohol or cannabis being the instigator rather than pharmacological drugs, even
      if outside the toxic origins, "drunkenness" may also occur without any substance
      intake: one can be drunk on love, poetry, music and even mania. Benzodiazepine
      "drunkenness" is not a classical notion in medicine. But the concept of
      addictology allows one to enlarge different approaches and to consider the
      relationship with psychoactive substances according to the same references. So,
      in a single fashion, between use and misuse, is it possible to resort to the same
      concepts for pharmacological drugs, including "drunkenness"? CLINICAL FINDINGS:
      Any intake of a psychoactive substance, limited in time, which will take the
      consumer some time to recover from, can be called simple use, intoxication or
      drunkenness. Intoxication is rather a classical medical concept linked with
      poisoning, and hence the toxicological aspects prevail particularly through the
      concept of a toxidrome. However, little research has been done on "drunkenness"
      in other medical aspects, neither psychological aspects nor sociological aspects.
      If poisoning is defined as soon as a poison is introduced into the body, the
      intoxication arises after a threshold (that toxicology usually defines), but no
      means are available to measure the onset of the inebriation, neither any ingested
      amounts nor any toxic concentration in the body. It is hard to define
      "drunkenness" simply. At first, it is most often seen as a pathology in medicine,
      unlike in every day life. "Drunkenness" can be the result of physiological
      disturbances, notably through the effects of substances and can therefore be the
      manifestation of a cerebral dysfunction. Alternatively, it can arise from a
      variation of emotional or sensorial stimuli. If the feelings associated with
      drunkenness are positive and pleasant a repetition will occur in the search to
      reproduce enjoyable effects in reference to neurophysiological models of reward
      systems of the brain, and can tend to be limited to a search for pleasure.
      Moreover, "drunkenness" may be considered as a leak, a regression or a kind of
      renouncement. It may sometimes be a search for sedation, for conscious sleep, or
      to avoid reality. And, finally, "drunkenness" may be suicidal. Since the launch
      of benzodiazepines on the market during the sixties, their prescription has
      developed, making them so readily available in France that they are nearly as
      easy to obtain as alcohol. The widespread diffusion of these psychoactive
      substances, obtained with or without medical prescription, renders them one of
      the principle means of chemically modulating thought and consciousness that has
      become accessible to all. One of the first reasons for this is the easy and wide
      prescription of these drugs by almost all practitioners. Choosing between
      benzodiazepines or alcohol (or associating both substances) is not fortuitous.
      Besides intoxication with pharmacological drugs, whether voluntary or otherwise,
      medication overdose and iatrogenic effects, there is an incidence of a
      substantial use of over the counter psychoactive drugs in order to trigger other
      effects than suicide or self-harm. This use of pharmacological drugs, sometimes
      referred to as "entertaining", can lead to massive intake with dramatic
      behavioural response. Is it then possible to use the same term "drunkenness" for
      a pharmacological drug-induced state as for a state provoked by other
      psychoactive substances with addictive potential ? The clinical presentation of
      benzodiazepine "drunkenness" resembles the pharmacological effects of these
      drugs. If we link alcoholic and benzodiazepine "drunkenness", we can draw a
      parallel between the properties, the action mechanisms, the effects and the risks
      incurred by the consumption of these two classes of psychotropics. The
      similarities concern the existence of a preclinical phase, of the same
      biochemical or neurophysiological basis, of the same properties, notably complex
      relationships with anxiety. They also have the same amnesiac effects, possible
      paradoxical effects, or sedation potentialities that may lead to coma,
      respiratory depression and death. But differences exist for benzodiazepines, in
      the lack of disinhibition effects, the lack of cerebellar effects, the
      variability of elimination kinetics according to the molecules, the rarity or the
      lack of "recreational" intakes, and the lack of easy blood level measurements.
      CONCLUSION: An attempt is made to outline the definition of benzodiazepine
      "drunkenness", including sociological, psychological, and medical dimensions
      beyond the sole toxicological aspects. So, studying the misuse of benzodiazepines
      in more detail including the acute effects such as "drunkenness", except suicidal
      or mortiferous tendencies, can allow further development of its recognition,
      screening and prevention.

PMID- 22381721
TI  - [Epidemiological and clinical characteristics of dissociative disorders and
      somatoform disorders in Burkina Faso].
AB  - OBJECTIVE: The aim of this study was to determine the epidemiological and
      clinical features of dissociative and somatoform disorders in the psychiatry
      department of the Centre Hospitalier Universitaire Yalgado Ouedraogo, in Burkina
      Faso. METHOD: We carried out a retrospective and descriptive study over five
      years, from January 2003 to December 2007, of patients admitted in the
      psychiatric department for dissociative and somatoform disorders. The data were
      extracted from the medical notes and registers of consultation. After
      identification of the patients, the medical notes were exploited with a
      structured collect form for data on sociodemographic characteristics, life events
      and ICD-10 diagnoses. All the data were recorded by the same person. Data
      analysis was performed with Epi info 2007. RESULTS: During a period of 5 years,
      3967 patients were registered, 179 had the diagnosis of dissociative and
      somatoform disorders (3.65% of the admissions) and 145 were included in our
      study. The majority of the patients were followed as outpatients (71%). Women
      were more represented with a sex ratio of four women to one man. The majority of
      the patients were young with an average age of 30 and mostly single (57.9%). The
      majority of the patients had a low academic standard, in connection with young
      age of the population. A striking biographic event was found in the majority of
      the cases; essentially family difficulties and death. Neurological symptoms were
      the most frequent in 63% of the cases. According to ICD-1O, dissociative
      disorders were most frequent (65.6%). Depression was mainly associated in15
      cases. DISCUSSION: Dissociative disorders and somatoform disorders are frequent
      in our hospital; we must overcome the difficulties due to the complexity of the
      diagnosis and the cultural resistances to modern health care to determine the
      real prevalence of these disorders among the population in Burkina Faso.

PMID- 22381722
TI  - [Body dysmorphic disorder and psychosis. Case reports and discussion].
AB  - INTRODUCTION: The diagnosis of patients who have a preoccupation about physical
      ugliness is not easy. Many diagnoses can be made. Body dysmorphic disorder (BDD)
      is defined as a preoccupation with an imaginary defect in physical appearance.
      What seems difficult in this diagnosis is to make the difference between the
      psychotic and the non-psychotic form of the disorder. If the patient becomes
      delusional, we have to make the diagnosis of delusional disorder, somatic
      subtype. Sometimes it is not easy to make the difference between the delusional
      and non-delusional form of the illness. A good example is the so-called
      "olfactory reference syndrome" (ORS), which involves the persistent preoccupation
      with one's body odour. To make it more difficult, the preoccupation with one's
      appearance can be seen in many other disorders, such as schizophrenia, or major
      depressive disorders. We present three cases of dysmorphophobic patients, to
      discuss their diagnosis and show how we have to be careful about this delusional
      versus non-delusional difference. CASE REPORTS: The first case is a young man,
      aged 20 year, who exhibits the typical picture of an ORS. He has probable
      olfactory hallucinations. He had good response to a treatment combining
      escitalopram 15mg and risperidone 1mg. The second case had a first appearance of
      BDD, but he had auditive hallucinations and the evolution showed a pattern more
      typical of schizophrenia, paranoid subtype. He responded initially to citalopram
      20mg and ripseridone 2mg. Sleepy with risperidone, it was shifted to amisulpiride
      200mg. After five years, it was possible to stop the amisulpiride, but we had to
      maintain it to avoid a relapse. The third case is typical of schizophrenia, with
      a pseudo neurotic aspect, and its course was terrible, with poor response to all
      neuroleptic therapy, including clozapine. DISCUSSION: These three cases are
      typical of a feature rarely reported in the literature: the delusional aspect of
      a dysmorphophobic concern. The literature mainly focuses on the more anxious
      pattern, and so emphasises the treatment with serotoninergic antidepressants. Our
      cases demonstrate a gradation in the delusional and psychotic aspect. The first
      case is dubitatively psychotic, the second is an "ambulatory" schizophrenia with
      a good response to treatment, the third a very destructive disease. In our cases,
      some features showed in the typical BDD are also present. We question the
      obsessive compulsive aspect of the disorder, which was present in our three
      cases. This supports the fact that the dysmorphophobic feature could be
      considered more like a symptom than a disorder itself. It reminds us to be always
      looking for the delusional features of a disorder so as to give the appropriate
      treatment.

PMID- 22381723
TI  - [Internet gambling: what are the risks?].
AB  - INTRODUCTION: Actually, there are many different and varied new ways to take part
      in gambling activities such as gambling via the Internet, mobile phone and
      interactive television. Among these media, the rise in Internet gambling activity
      has been very rapid. Nevertheless, few empirical studies have been carried out on
      the psychosocial effects of Internet gambling. While there is no conclusive
      evidence that Internet gambling is more likely than other gambling media to cause
      problem gambling, there are a number of factors that make online activities like
      Internet gambling potentially seductive and/or addictive. Such factors include
      anonymity, convenience, escape, dissociation/immersion, accessibility, event
      frequency, interactivity, disinhibition, simulation, and asociability. It would
      also appear that virtual environments have the potential to provide short-term
      comfort, excitement and/or distraction. BACKGROUND: The introduction of the
      Internet to gambling activities changes some of the fundamental situational and
      structural characteristics. The major change is that gambling activities are
      bought into the home and workplace environment. Thus, Internet gambling can
      become an in-house or work activity. One of the major concerns relating to those
      changes and the increase in gambling opportunities is the potential rise in the
      number of problem and pathological gamblers. Addictions always result from an
      interaction and interplay between many factors but in the case of gambling, it
      could be argued that technology and technological advance can themselves be an
      important contributory factor as we saw in examining the salient factors in
      Internet gambling. It is difficult to determine the prevalence of online (problem
      or not) gamblers, as it is obviously a figure that changes and has changed
      relatively quickly over the past decade. Nevertheless, the rate of Internet
      gambling is increasing and some recent studies using self-selected samples
      suggest, for example, that the prevalence of problem gambling among student
      Internet gamblers is relatively high for students who gamble on the Internet in
      general. LITERATURE FINDINGS: Some recent studies have focused on the type of
      online games. For example, one specific form of online gambling online poker, is
      one of the fastest growing forms of online gambling. It appears that problem
      online poker players are more likely to swap genders when playing online, and
      play more frequently for longer periods of time. Thus, problem gamblers may be
      losing time but winning money. This result has a big implication for problem
      gambling criteria. Indeed, some data suggest that online poker may be producing a
      new type of problem gambler where the main negative consequence is loss of time
      (rather than loss of money). CONCLUSION: All these findings underline the need
      for better Internet gambling legislation. Indeed, the potential for excessive
      gambling and the lack of safeguards for vulnerable populations (e.g. adolescents
      and problem gamblers) raise the need for developing social responsibility tools.
      Harm-minimisation strategies are fundamental to facilitate gambling in a
      responsible manner, that is, to promote gambling within a player's means so they
      do not spent excessive time or money gambling, which cause the individual
      problems. Some research, but still few, examines the efficacy of responsible
      gambling strategies like pop-up messages.

PMID- 22381724
TI  - [The placebo effect: general information and specificities in psychiatry
      (depression and schizophrenia)].
AB  - INTRODUCTION: Placebos, consequences of their use, the placebo effect and the
      associated negative effects, the nocebo effect, have been widely studied.
      However, the lack of any consensus definition makes the interpretation and
      analysis of such findings difficult. LITERATURE FINDINGS: In this article, we
      will review existing definitions and factors affecting the placebo effect in
      medicine. We will then consider the possible mechanisms of action of the placebo
      effect, with a view to improving understanding of this issue. Finally, we will
      analyse data relating to placebos used in psychiatry and, more specifically, for
      schizophrenic patients. In an extensive review of the literature, we identified
      the various factors playing a role in the appearance of placebo effects in
      general medicine. As well as purely factual elements, such as the disorder, the
      sex of the subject and the treatment given, the placebo effect is strongly
      correlated with the quality of the relationship between the doctor and patient
      and with the capacity of the patient to communicate and establish a link. The
      attitude of the doctor, the temperament of the subject and the expectations and
      beliefs of each also contribute to the appearance and extent of a placebo effect.
      We then investigated placebo effects in psychiatry, particularly in depressed
      patients (the most widely studied condition) where studies have shown particular
      efficacy. We also addressed the use of placebos in schizophrenia: the placebo
      effect in patients with this disorder is essentially used as a tool for assessing
      new molecules to be released onto the market but the phenomenon itself has been
      little studied, if at all. Thus, it is of particular interest to consider in
      detail the use of placebos in schizophrenia, to try to gain a deeper
      understanding of the factors involved. This will allow potential specific effects
      associated with placebo use in this disorder to be established, improving the
      integration of placebos into therapy and to optimize the efficacy of treatment
      prescribed, taking into account mental state; indeed, the placebo effect is
      present in all treatments, whether involving a placebo or an active compound.

PMID- 22381725
TI  - [Review of cases of prolonged QTC and wave burst arrhythmia in patients treated
      with methadone].
AB  - INTRODUCTION: For the past 40 years, methadone has been known to be an efficient
      treatment of substitution. Its use allowed a significant reduction in the
      mortality related to opioid addiction. Since 2001, many articles have reported
      some cases of syncope, wave burst arrhythmia, ventricular tachycardia due to
      prolonged QT interval and sudden death secondary to cardiac arrest, with a risk
      of prolongation of the QT interval above 440 ms (men) and 460 ms (women). Many
      explorations have helped in understanding the physiopathology by showing that
      opioids, including methadone, cause a blockage of the potassium channels of the
      gene HERG K+P. This event could slow the repolarisation and the atrioventricular
      cardiac synchronization and could induce ventricular arrhythmia. LITERATURE
      FINDINGS: Nearly 20 studies showed a prolonged QT interval secondary to methadone
      in patients exhibiting the following features: (1) patients with cardiac
      pathologies, notably bradycardia, congenital long QT interval, myocardial
      pathologies related to AIDS and electrolyte disturbances; (2) patients receiving
      concomitant treatment with substances known to prolong QT interval, such as
      psychoactive stimulants, narcoleptics, tricyclic antidepressants, antiarrhythmic
      agents, macrolids, quinolones, non diuretic hypokalemiants and certain
      corticoids; (3) patients receiving treatments that inhibit methadone's
      metabolism, particularly those that act on the cytochrome P450 3A4 such as SSRI,
      antifungal agents, some macrolids and some retroviral agents. Many recent
      studies, while evaluating the dose-dependent effect of methadone on the QT
      prolongation, showed a tendency to a prolonged QT when using higher doses of
      methadone. CONCLUSION: Screening for these risk factors should be carried out
      before prescribing methadone. EKG should not be systematically performed unless
      the conditions described above are present or if a higher dose of methadone is
      needed.

PMID- 22381726
TI  - [REALITE LT, a pharmacoepidemiological study of semiology and therapeutic
      strategy of patients with schizophrenia treated by antipsychotic loxapine in
      routine clinical practice].
AB  - INTRODUCTION: Data concerning the clinical and therapeutic characteristics of
      patients with schizophrenia treated by antipsychotic in naturalistic conditions
      are useful. Two national pharmacoepidemiological studies were conducted in
      France, a retrospective survey REALITE and a prospective study REALITE LT, to
      examine the use of loxapine, first in acute and chronic psychotic states and
      second in long-term treatment prescribed for patients with schizophrenia. AIM OF
      STUDY: The aim of REALITE LT is to specify the clinical characteristics of
      schizophrenic patients treated by loxapine for at least 4 months and the
      description of the methods of use of this antipsychotic medication during a 6
      month follow-up in "real life" conditions. DESIGN OF STUDY: REALITE LT is an
      epidemiologic, observational, longitudinal, prospective (during a half-year
      period), multicenter and national study of the prescription of loxapine in
      routine clinical practice. For this study, 645 patients with schizophrenia
      treated by loxapine were recruited, assessed by PANSS, CGI, GAF, MeDra-SOC-PT for
      side effects and Girerd questionnaire for compliance; statistical analysis used
      SAS 9.2. RESULTS: Six hundred and forty-five adult patients were included and
      assessed at inclusion, month 3 and 6. These patients were mostly male (69%), with
      an average age of 41, inactive (68%), lonely with no child (79%), under
      psychiatric care for more than 5 years (81%), less than one third were
      inpatients. The subtypes of schizophrenia were paranoid (59%), disorganised
      (21%), undifferentiated or residual (10%), the outcome of psychotic illness was
      episodic (50%) or continuous (33%). The daily mean dosage of loxapine was 168,4
      mg/d, in antipsychotic loxapine monotherapy (27%) or in combination with other
      antipsychotics (63%); it was often associated with psychotropic medications
      (anxiolytic [72%], antidepressant [21%], normothymic [19%]). The stability of the
      dosage of loxapine during the 6 months follow-up (60%) was associated with strict
      loxapine monotherapy or antipsychotic monotherapy (loxapine associated with other
      psychotropic medication). Safety, side effects and compliance were compared with
      previous studies. DISCUSSION AND CONCLUSION: These results are discussed,
      comparing the two pharmacoepidemiological studies REALITE and REALITE LT,
      loxapine is used in compliance with the two indications (smpc) and French
      guidelines (HAS, Haute Autorite de sante).

PMID- 22381727
TI  - [Treatment practices in the management of patients with bipolar disorder in
      France. The TEMPPO study].
AB  - TEMPPO is an observational, cross-sectional and multicentre study, initiated in
      the French metropolitan territory in 2009. Set up from a random sample of 135
      psychiatrists, it has observed the procedures for therapeutic management of a
      population (n=619) of their outpatients (respectively 197 and 422 in public and
      private practice) with bipolar disorder type I or II disorders (DSM-IV). The
      patients who were followed were mostly very sick. Every patient received a
      pharmacological treatment. The prescription included at least one mood stabilizer
      or an antipsychotic (71 % atypical) in 78 % and 56 % of cases respectively.
      Treatment regimen changes were frequent (61 % of patients had at least one change
      in treatment during the last 12 months). A single molecule by therapeutic class
      was generally prescribed. The presence of an antipsychotic in combination therapy
      was often associated with the severity or difficulty of care of the patient
      (mixed states, severity of the global functioning impairment, manic states, high
      number of hospitalizations and history of suicide attempt). The combination of
      two antipsychotics is found only in the difficult situations of manic states.
      Patients with severe depressive phase are those who benefit from the combination
      mood stabilizer+antipsychotic+antidepressant (16 % of the sample). In this study,
      the prescription of antidepressants significantly differs from recommendations
      for good prescribing practices. Indeed antidepressants were commonly prescribed
      in mixed-phase (63 %), particularly as a monotherapy in 5 % of cases. It was also
      found in patients in euthymic phase (48 %), manic phase (12 %) and hypomanic
      phase (29 %). The prescription of atypical antipsychotics (monotherapy or
      combination) is now fully established in the management of all phases of the
      disease. The importance of non-pharmacological treatment is acknowledged by
      psychiatrists and proposed whether a psychotherapeutic support, information about
      the disease and/or lifestyle changes. The data collected in this study allowed to
      demonstrate that the participant psychiatrists have a pharmacological management
      of patients with bipolar disorder mostly in line with national and international
      guidelines.

PMID- 22381728
TI  - [Clinical efficacy and achievement of a complete remission in depression:
      increasing interest in treatment with escitalopram].
AB  - Such a prevalent disease as Major Depressive Disorder (MDD), associated with
      prominent impairment in physical and social functioning, implies as well an
      increased morbidity and mortality. Long-term treatments are required due to the
      frequent occurrence of relapses. Patient compliance is a core factor in both
      acute and continuation treatment, closely related to tolerability issues. We have
      partially reviewed the literature published on PubMed since 2004 which assess the
      relative antidepressant efficacy of escitalopram and comparator antidepressants
      in adult patients who met DSM-IV criteria for major depressive disorder (MDD).
      Clinically important differences exist between commonly prescribed
      antidepressants. These analyses are in favor of a superior efficacy and
      tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with
      active controls, including selective serotonin re-uptake inhibitors (SSRIs)
      (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline),
      serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and
      duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs)
      (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of
      12 new generation antidepressants. They have shown that clinically important
      differences exist between commonly prescribed antidepressants for both efficacy
      and acceptability in favor of escitalopram and sertraline in acute treatment,
      defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled
      analysis of data from two 6-month randomized controlled trials that revealed
      superior efficacy and tolerability of escitalopram when compared with paroxetine.
      The pooled analysis of four randomized, double-blind, active comparator, 6-month
      trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict
      long-term treatment compliance and outcomes. A higher probability of achieving
      remission was associated with responding after 8 weeks and with completing 6
      months of treatment. Furthermore, Week 24 complete remission (MADRS<=5) was
      significantly (P<0,01) higher for escitalopram (51.7%) than for the pooled
      comparators (45.6%). And after 6 months, fewer patients discontinued treatment
      with escitalopram (15.9%) than with the pooled comparators (23.9%) (P<0.001).
      This fragmentary review of the literature shows that it is necessary to adopt a
      stringent definition of remission in depression, especially in clinical trials; a
      MADRS total score less or equal to 10 to define remission, a MADRS total score
      less or equal to 5 to define complete remission, and moreover no MADRS single
      item greater than 1 to define symptom-free remission. In all these meta-analyses,
      the superiority of escitalopram compared with other antidepressants was confirmed
      for both acute and long-term treatment of MDD, especially in harshly depressed
      patients.

PMID- 22381729
TI  - [Study on how schizophrenic patients perceive treatment with injections in the
      deltoid muscle].
AB  - Despite the advantages of antipsychotic treatments via the injectable route of
      administration, there are still reservations regarding this type of therapy,
      notably among health professionals. A survey conducted with patients suffering
      from schizophrenic disorders revealed the positive opinion that they had of their
      treatment. Another survey showed that nearly half of the patients preferred an
      injectable form, and two thirds felt they were cared for better, because of the
      injectable treatment. The slow release form of risperidone allows a choice
      between two injection sites: the deltoid muscle or the gluteal muscle. A recent
      study showed the satisfaction of the health professionals towards this novel
      form. The survey presented here was aimed at collecting the opinion of patients
      regarding the possibility of choosing the injection site, and the changes it
      would make. OBJECTIVES AND METHODS: The survey was carried out by the BVA
      Institute during the first half of 2011. The interviews with the schizophrenic
      patients, followed-up as out patients and treated with long lasting
      antipsychotics (n=281), were conducted face to face at the hospital by BVA
      interviewers specialised in the field of health, without the presence of any
      health professionals. A total of 32 centres participated in the survey; 38% of
      the interviews took place in the Paris area and 62% in various regions. RESULTS:
      Different dimensions were analysed. (1) The perception of injectable treatment
      was largely positive: among all the patients, 75% claimed they currently felt
      better once they had started the injectable treatment. (2) The choice of the
      injection site appeared important to a majority of patients (70% of the total
      sample; 79% of patients had experienced both sites of injection), 56% claimed
      that it was legitimate that they be given the choice and they felt that they were
      thus able to participate in their treatment (58%), their treatment was more
      acceptable (54%), and they found that their relationship with the doctor or nurse
      was enhanced (53%). (3) The preference regarding the injection site went to the
      deltoid muscle, among those who had experienced both sites. (4) The perception of
      the injection sites confirms this preference, the positive qualifications often
      being associated with the deltoid site, and the negative qualifications with the
      gluteal site. CONCLUSION: The survey presented here could contribute in
      convincing the health professionals to propose the choice to patients between the
      two injection sites in order to improve their compliance to treatment. Patients
      would therefore play a role in the choice of their treatment and hence become
      more involved in the follow-up.

PMID- 22381730
TI  - [Case report: electroconvulsive therapy in a 33-year-old man with hysterical
      quadriplegia].
AB  - Conversion disorder refers to the occurrence of neurological-like symptoms or
      deficits that are neither intentionally produced nor simulated. While it cannot
      be explained by an organic disease, it is often related to psychological events.
      CASE REPORT: We report the case of a 33-year-old patient with a fluctuating
      hysterical tetraplegia, which had started three years earlier. After the failure
      or the exhaustion of several biological (psychotropic medication, transcranial
      magnetic stimulation) and psychotherapeutic strategies, treatment with
      electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT
      sessions were performed. Whereas the patient's clinical state was initially
      characterized by a complete quadriplegia and an uncontrollable muscular
      hypertonia, we noted that the ECT sessions were associated with a slow, though
      remarkable, progress. At first, the sessions were followed by moments of altered
      consciousness during which the patient would be relaxed and could make simple
      movements. Secondarily, not only was our patient able to consciously move his
      four limbs, but he was also able to walk. However, those improvements remained
      partial and fluctuating, sometimes allowing the symptom to return temporarily
      secondary to frustrations or annoyances. Finally, our patient relapsed.
      Nevertheless, his clinical state presently remains better than that in which we
      first knew him. DISCUSSION: The treatment of conversion disorders has been the
      subject of few studies and predominantly remains symptomatic. Its main goals are:
      to lessen secondary gains impact by adopting a neutral behaviour towards the
      symptom and by encouraging physical rehabilitation; to lower the symptom by
      allowing the patient to understand the normal functioning of the diseased organ,
      and; to help the patient to deal with stressful situations. There is no evidence
      that hypnosis is superior to medical and other psychotherapeutic approaches.
      Pharmacological treatments may be helpful in the case of anxiety, impulsivity or
      depression, albeit delivered with caution. According to some case reports,
      transcranial magnetic stimulation has also been associated with clinical
      remission. Although the use of ECT in motor conversion disorders constitutes an
      uncommon procedure, and even if no clinical trial has evaluated its impact on
      such a pathological condition, several case reports suggest that
      electroconvulsive therapy can be efficient in the treatment of motor conversion
      disorders. This efficacy may rely on several hypotheses. ECT could induce neural
      modifications, and participate in the suppression of an active inhibition, which
      is responsible for hysterical symptoms. Indeed, conversion cerebral disorder
      correlates can be explored with the help of functional neuro-imaging techniques,
      which could therefore also identify ECT neural effects. ECT adverse effects on
      memory could lead to a new relationship with the symptom, and modulate the
      psychological conflict which has participated in its emergence. Narcoanalysis,
      ECT sessions could have an impact on consciousness by means of some dissolution
      and reorganization phenomenon. It could therefore participate in the ending of an
      emotional block, the psychic integration of traumatic events and the recovery of
      a voluntary motor control. Finally, ECT could be efficient thanks to its
      antidepressant properties, especially its ability to stimulate triaminergic, and
      particularly dopaminergic transmission. This case report reminds us how difficult
      it can be to deal with severe conversion disorders, and to navigate between two
      reefs, which are abstention, and therapeutic escalation.

PMID- 22381731
TI  - Insights into cortical oscillations arising from optogenetic studies.
AB  - Cortical oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency
      range have been hypothesized to play important roles in numerous cognitive
      processes and may be involved in psychiatric conditions including anxiety,
      schizophrenia, and autism. This review provides background information about
      these oscillations and their possible roles in psychiatric illness. Findings from
      recent studies that used optogenetic tools to demonstrate that 1) a particular
      class of inhibitory interneurons expressing the calcium binding protein
      parvalbumin plays a central role in gamma oscillations, 2) gamma oscillations can
      entrain rhythmic firing in pyramidal neurons, and 3) rhythmic firing at theta and
      gamma frequencies can enhance communication between neurons are described.
      Finally, how these findings may relate to the pathophysiology of psychiatric
      conditions, as well as questions for future studies, are discussed.

PMID- 22381733
TI  - Cerebral hemodynamics and incident depression: the Rotterdam Study.
AB  - BACKGROUND: According to the vascular depression hypothesis, subclinical
      cerebrovascular disease can cause depression in older adults. To test this
      hypothesis, several cross-sectional studies have assessed structural brain
      parameters, but few have examined hemodynamic alterations in the brain. METHODS:
      From the Rotterdam Study, we studied a cohort of 1494 participants (65+ years of
      age) free of depression, dementia, and stroke at baseline. In the middle cerebral
      artery blood flow velocities and vasomotor reactivity were measured with
      transcranial Doppler ultrasonography. All participants were repeatedly assessed
      for depressive symptoms with Centre for Epidemiological Studies-Depression scale
      (CES-D). Participants with depressive symptoms (CES-D >=16) had a semi-structured
      interview, to classify the depression according to DSM-IV criteria. All analyses
      were adjusted for sociodemographic data, vascular risk factors, and incident
      stroke. RESULTS: Lower peak-systolic, end-diastolic, and mean blood flow
      velocities at baseline were associated with higher CES-D scale scores at follow
      up. Mean blood flow velocity predicted incident depressive symptoms (odds ratio
      [OR]: .74, 95% confidence interval [CI]: .60-.91, p = .004) and depressive
      disorders (OR: .83, 95% CI: .69-.98, p = .032), whereas decreased baseline
      vasomotor reactivity predicted incident depressive disorders only (OR: .66, 95%
      CI: .53-.83, p < .001). CONCLUSIONS: Lower blood flow velocity, indicating
      reduced cerebral metabolism, predicted depressive symptoms and depressive
      disorders. Reduced vasomotor reactivity, which might indicate cerebral
      microangiopathy, predicted depressive disorders only, in healthy older adults.
      These findings provide prospective evidence for vascular depression hypothesis.

PMID- 22381732
TI  - Reversal of impaired hippocampal long-term potentiation and contextual fear
      memory deficits in Angelman syndrome model mice by ErbB inhibitors.
AB  - BACKGROUND: Angelman syndrome (AS) is a human neuropsychiatric disorder
      associated with autism, mental retardation, motor abnormalities, and epilepsy. In
      most cases, AS is caused by the deletion of the maternal copy of UBE3A gene,
      which encodes the enzyme ubiquitin ligase E3A, also termed E6-AP. A mouse model
      of AS has been generated and these mice exhibit many of the observed neurological
      alterations in humans. Because of clinical and neuroanatomical similarities
      between AS and schizophrenia, we examined AS model mice for alterations in the
      neuregulin-ErbB4 pathway, which has been implicated in the pathophysiology of
      schizophrenia. We focused our studies on the hippocampus, one of the major brain
      loci impaired in AS mice. METHODS: We determined the expression of neuregulin 1
      and ErbB4 receptors in AS mice and wild-type littermates (ages 10-16 weeks) and
      studied the effects of ErbB inhibition on long-term potentiation in hippocampal
      area cornu ammonis 1 and on hippocampus-dependent contextual fear memory.
      RESULTS: We observed enhanced neuregulin-ErbB4 signaling in the hippocampus of AS
      model mice and found that ErbB inhibitors could reverse deficits in long-term
      potentiation, a cellular substrate for learning and memory. In addition, we found
      that an ErbB inhibitor enhanced long-term contextual fear memory in AS model
      mice. CONCLUSIONS: Our findings suggest that neuregulin-ErbB4 signaling is
      involved in synaptic plasticity and memory impairments in AS model mice,
      suggesting that ErbB inhibitors have therapeutic potential for the treatment of
      AS.

PMID- 22381734
TI  - MAGI1 copy number variation in bipolar affective disorder and schizophrenia.
AB  - BACKGROUND: Bipolar affective disorder (BPAD) and schizophrenia (SZ) are
      devastating psychiatric disorders that each affect about 1% of the population
      worldwide. Identification of new drug targets is an important step toward better
      treatment of these poorly understood diseases. METHODS: Genome-wide copy number
      variation (CNV) was assessed and variants were ranked by co-occurrence with
      disease in 48 BPAD families. Additional support for involvement of the highest
      ranking CNV from the family-based analysis in psychiatric disease was obtained
      through analysis of 4084 samples with BPAD, SZ, or schizoaffective disorder.
      Finally, a pooled analysis of in-house and published datasets was carried out
      including 10,925 cases with BPAD, SZ, or schizoaffective disorder and 16,747
      controls. RESULTS: In the family-based analysis, an approximately 200 kilobase
      (kb) deletion in the first intron of the MAGI1 gene was identified that
      segregated with BPAD in a pedigree (six out of six affected individuals;
      parametric logarithm of the odds score = 1.14). In the pooled analysis, seven
      additional insertions or deletions over 100 kb were identified in MAGI1 in cases,
      while only two such CNV events were identified in the same gene in controls (p =
      .023; Fisher's exact test). Because earlier work had identified a CNV in the
      close relative MAGI2 in SZ, the study was extended to include MAGI2. In the
      pooled analysis of MAGI2, two large deletions were found in cases, and two
      duplications were detected in controls. CONCLUSIONS: Results presented herein
      provide further evidence for a role of MAGI1 and MAGI2 in BPAD and SZ etiology.

PMID- 22381735
TI  - Volar/dorsal compressive mechanical behavior of the transverse carpal ligament.
AB  - Mechanical insult to the median nerve caused by contact with the digital flexor
      tendons and/or carpal tunnel boundaries may contribute to the development of
      carpal tunnel syndrome. Since the transverse carpal ligament (TCL) comprises the
      volar boundary of the carpal tunnel, its mechanics in part govern the potential
      insult to the median nerve. Using unconfined compression testing in combination
      with a finite element-based optimization process, nominal stiffness measurements
      and first-order Ogden hyperelastic material coefficients (MU and alpha ) were
      determined to describe the volar/dorsal compressive behavior of the TCL. Five
      different locations on the TCL were tested, three of which were deep to the
      origins of the thenar and hypothenar muscles. The average (+/- standard
      deviation) low-strain and high-strain TCL stiffness values in compression sites
      outside the muscle attachment region were 3.6 N/mm (+/-2.7) and 28.0 N/mm (+/
      20.2), respectively. The average stiffness values at compression sites with
      muscle attachments were notably lower, with low-strain and high-strain stiffness
      values of 1.2 N/mm (+/-0.5) and 9.7 N/mm (+/-4.8), respectively. The average
      Ogden coefficients for the muscle attachment region were 51.6 kPa (+/-16.5) for
      MU and 16.5 (+/-2.0) for alpha, while coefficients for the non-muscle attachment
      region were 117.8 kPa (+/-86.8) for MU and 17.2 (+/-1.6) for alpha. These TCL
      compressive mechanical properties can help inprove computational models, which
      can be used to provide insight into the mechanisms of median nerve injury leading
      to the onset of carpal tunnel syndrome symptoms.

PMID- 22381736
TI  - Biomechanical correlates of symptomatic and asymptomatic neurophysiological
      impairment in high school football.
AB  - Concussion is a growing public health issue in the United States, and chronic
      traumatic encephalopathy (CTE) is the chief long-term concern linked to repeated
      concussions. Recently, attention has shifted toward subconcussive blows and the
      role they may play in the development of CTE. We recruited a cohort of high
      school football players for two seasons of observation. Acceleration sensors were
      placed in the helmets, and all contact activity was monitored. Pre-season
      computer-based neuropsychological tests and functional magnetic resonance imaging
      (fMRI) tests were also obtained in order to assess cognitive and
      neurophysiological health. In-season follow-up scans were then obtained both from
      individuals who had sustained a clinically-diagnosed concussion and those who had
      not. These changes were then related through stepwise regression to history of
      blows recorded throughout the football season up to the date of the scan. In
      addition to those subjects who had sustained a concussion, a substantial portion
      of our cohort who did not sustain concussions showed significant
      neurophysiological changes. Stepwise regression indicated significant
      relationships between the number of blows sustained by a subject and the ensuing
      neurophysiological change. Our findings reinforce the hypothesis that the effects
      of repetitive blows to the head are cumulative and that repeated exposure to
      subconcussive blows is connected to pathologically altered neurophysiology.

PMID- 22381737
TI  - Mechanical property changes during neonatal development and healing using a
      multiple regression model.
AB  - During neonatal development, tendons undergo a well orchestrated process whereby
      extensive structural and compositional changes occur in synchrony to produce a
      normal tissue. Conversely, during the repair response to injury, structural and
      compositional changes occur, but a mechanically inferior tendon is produced. As a
      result, developmental processes have been postulated as a potential paradigm for
      elucidation of mechanistic insight required to develop treatment modalities to
      improve adult tissue healing. The objective of this study was to compare and
      contrast normal development with injury during early and late developmental
      healing. Using backwards multiple linear regressions, quantitative and objective
      information was obtained into the structure-function relationships in tendon.
      Specifically, proteoglycans were shown to be significant predictors of modulus
      during early developmental healing but not during late developmental healing or
      normal development. Multiple independent parameters predicted percent relaxation
      during normal development, however, only biglycan and fibril diameter parameters
      predicted percent relaxation during early developmental healing. Lastly, multiple
      differential predictors were observed between early development and early
      developmental healing; however, no differential predictors were observed between
      late development and late developmental healing. This study presents a model
      through which objective analysis of how compositional and structural parameters
      that affect the development of mechanical parameters can be quantitatively
      measured. In addition, information from this study can be used to develop new
      treatment and therapies through which improved adult tendon healing can be
      obtained.

PMID- 22381738
TI  - Improving the validation of finite element models with quantitative full-field
      strain comparisons.
AB  - The techniques used to validate finite element (FE) models against experimental
      results have changed little during the last decades, even though the traditional
      approach of using single point measurements from strain gauges has major
      limitations: the strain distribution across the surface is not captured and the
      accurate determination of strain gauge positions on the model surface is
      difficult if the 3D surface topography of the bone surface is not measured. The
      full-field strain measurement technique of digital speckle pattern interferometry
      (DSPI) can overcome these problems, but the potential of this technique has not
      yet been fully exploited in validation studies. Here we explore new ways of
      quantifying and visualising the variation in strain magnitudes and orientations
      within and between repeated DSPI measurements as well as between the DSPI
      measurements and FEA results. We show that our approach provides a much more
      comprehensive and accurate validation than traditional methods. The measurement
      repeatability and the correspondence between measured and predicted strains vary
      to a great degree within and between measurement areas. The two models used in
      this study predict the measured strain directions and magnitudes surprisingly
      well considering that homogeneous and isotropic mechanical properties were
      assigned to the models. However, the full-field comparisons also reveal some
      discrepancies between measured and predicted strains that are most probably
      caused by inaccuracies in the models' geometries and the degree of simplification
      of the modelled material properties.

PMID- 22381739
TI  - Prestress as an optimal biomechanical parameter for needle penetration.
AB  - Drug delivery requires precise intradermal and subcutaneous injections of
      formulations to clinically relevant penetration depths. However, penetration
      depth is confounded by skin deflection, which occurs prior to and during
      penetration as the skin surface deforms axially with the needle, and which varies
      profoundly due to differing intrinsic mechanical (e.g. viscoelastic) tissue
      properties, disease state, aging, and ethnicity. Herein, an ex vivo model was
      utilized to study factors that affect skin deflection and the efficacy of
      injection, including prestress applied at the tissue surface, needle gauge,
      velocity, and actuation depth. The application of prestress minimized skin
      deflection during needle penetration and allowed for needle actuation to the
      targeted penetration depths with minimum variability. The force required to
      achieve target penetration depths was found to increase with prestress and
      decrease with needle gauge. Our findings emphasize the need for prestress applied
      to the skin surface to minimize variation in skin properties and administer
      formulations for intradermal and subcutaneous treatments with maximum precision.

PMID- 22381740
TI  - Acute initial haemodynamic changes in a rat isoprenaline model of cardiotoxicity.
AB  - The synthetic catecholamine isoprenaline (ISO) has been used as an inductor in
      the acute myocardial infarction model for more than a half century. Despite the
      fact that many articles were published on this topic, precise early haemodynamic
      pathology remains unknown. Acute haemodynamic changes were measured in rats;
      first, in preliminary experiments by the thermodilution method; and second, in
      main experiments continuously for 2 h using a Millar catheter. Animals received
      saline or ISO in the cardiotoxic dose (100 mg/kg, subcutaneously). Also,
      additional experiments were performed with salbutamol in order to evaluate the
      role of beta(2)-receptors. ISO caused a rapid, within 1 min, approximately 40%
      decrease in arterial blood pressures, 30% increase in the heart rate, and 30%
      decrease in the stroke volume. Within the first 2 min, the changes were followed
      by decreases in afterload (-40%), preload (-10%), diastolic relaxation (-50%),
      diastolic filling (-40%), and a marked, but short-term, increase in the left
      ventricle contractility (+100%). Ejection fraction did not significantly change,
      suggesting diastolic dysfunction. Salbutamol, with the exception of diastolic
      pressure and afterload, did not substantially influence other parameters. In
      conclusion, this study demonstrated that diastolic dysfunction precedes systolic
      dysfunction and beta(2)-receptor stimulation alone is not sufficient for an early
      induction of diastolic dysfunction.

PMID- 22381741
TI  - Sulfasalazine prevents the increase in TGF-beta, COX-2, nuclear NFkappaB
      translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.
AB  - It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor
      kappaB (NFkappaB) pathway, which regulates important genes during inflammation
      and immune answer. The aim of this work was to evaluate the effects of SF on
      carbon tetrachloride (CCl(4))-induced liver fibrosis. We formed the following
      experimental groups of rats: controls, damage induced by chronic CCl(4) (0.4
      g/kg, intraperitoneally, three times a week for 8 weeks) administration and
      CCl(4) + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We
      determined the activities of alanine aminotransferase (ALT), gamma-glutamyl
      transpeptidase (gamma-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation,
      glutathione levels, collagen content, expression of transforming growth factor
      beta (TGF-beta) and nuclear translocation of NFkappaB. SF was capable to inhibit
      the ALT and gamma-GTP elevated levels induced with the CCl(4) administration. SF
      had antioxidant properties, prevented the lipid peroxidation and the imbalance of
      reduced and oxidized glutathione produced by CCl(4). Importantly, SF blocked the
      accumulation of collagen in the liver, the expression of TGF-beta, the nuclear
      translocation of NFkappaB and the activity of COX-2, all induced with the
      administration of CCl(4) in the rat. These results show that SF has strong
      antifibrotic properties because of its antioxidant properties and its ability to
      prevent nuclear translocation of NFkappaB and consequently the expression of TGF
      beta and the activity of COX-2.

PMID- 22381742
TI  - Sex hormones and cardiac arrest in long QT syndrome: does progesterone represent
      a potential new antiarrhythmic therapy?

PMID- 22381743
TI  - Arsenic toxicity: a heart-breaking saga of a freshwater mollusc.
AB  - The freshwater wetland systems of India is a complex habitat that supports a
      broad range of diverse species including molluscs, which play an important role
      in supplementing third world countries. In the arsenic affected flood plains of
      West Bengal, a huge amount of arsenic laden groundwater is raised for the purpose
      of irrigation. Agricultural runoffs and flood water movement during monsoon may
      cause accumulation of arsenic in the adjacent freshwater aquifers, the common
      habitat of Lamellidens marginalis (Mollusca; Bivalvia; Eulamellibranchiata), a
      filter feeder, sensitive to altered environmental conditions. To examine the
      nature of toxicity induced by inorganic arsenic on both the haemocytes and
      tissues of the invertebrate heart, the animals were exposed to five different
      sublethal concentrations of sodium arsenite for a maximum time span of 30 days in
      vitro. Significant differences were recorded in the total haemocyte count,
      biochemical and histopathological parameters of the heart of L. marginalis under
      the arsenic induced stress. Our observations indicate the development of profound
      haematopoietic and cardiac stress under the sublethal inorganic arsenite exposure
      and it also implies the nature of risk imposed on the freshwater aquatic
      ecosystem under potential arsenic contamination.

PMID- 22381744
TI  - [Role of P38 signaling pathway in neonatal rat astrocyte swelling and aquaporin-4
      expression after oxygen-glucose deprivation and recovery].
AB  - OBJECTIVE: To explore the role of P38 signaling pathway in neonatal rat astrocyte
      swelling and the expression of aquaporin-4 (AQP4) after oxygen-glucose
      deprivation (OGD) and recovery (OGD/R). METHODS: Primarily cultured neonatal rat
      astrocytes were subject to OGD for 5 h followed by oxygen-glucose recovery in the
      presence or absence of the P38 inhibitor SB203580 (10 umol/L). The astrocytes
      were investigated at 0.5, 2, 8 and 24 h after oxygen-glucose recovery for
      morphological changes and cell injuries using lactate dehydrogenase (LDH) assay.
      The expressions of P38, P-P38, and AQP4 mRNAs and proteins in the astrocytes were
      detected using RT-PCR and Western blotting. RESULTS: OGD/R caused significantly
      enhanced expression of P-P38 protein, and this effect was blocked by SB203580.
      AQP4 mRNA and protein expression declined transiently at 0.5 h after OGD and
      increased gradually to reach the peak level at 8 h (P<0.05). Application of the
      SB203580 significantly lowered OGD-induced AQP4 mRNA and protein up-regulation
      (P<0.05). Astrocyte swelling occurred after OGD/R but was obviously lessened by
      SB203580. LDH release increased markedly after OGD/R, and was attenuated by
      treatment with SB203580 (P<0.01). CONCLUSION: P38 signaling pathway participates
      in astrocyte swelling after OGD/R, and blocking this pathway can attenuate AQP4
      up-regulation and ameliorate the cell swelling.

PMID- 22381745
TI  - [Mouse melanoma cell line B16F10-derived conditioned medium inhibits  sodium L
      ascorbate-induced B16F10 cell apoptosis].
AB  - OBJECTIVE: To investigate the effect of mouse melanoma cell line B16F10-derived
      conditioned medium on the apoptosis of B16F10 cells. METHODS: B16F10 cells were
      cultured in high-glucose DMEM in the presence of 10% fetal bovine serum, and upon
      cell confluence, the growth medium was replaced with serum-free high-glucose
      DMEM. After 8 h, the medium was collected and infiltrated to serve as the
      conditioned medium. B16F10 cells cultured in normal growth medium or the
      conditioned medium were exposed to 10 mmol/L sodium L-ascorbate, and the cell
      apoptosis was analyzed. The ingredients in the conditioned medium with relative
      molecular mass less or more than 5 000 were extracted to assess their effect on
      sodium L-ascorbate-induced cell apoptosis. RESULTS: The conditioned medium for
      B16F10 cells significantly inhibited cell apoptosis induced by sodium L
      ascorbate, and the effective ingredients in the medium showed a relative
      molecular mass below 5,000. CONCLUSION: Mouse melanoma cell line B16F10-derived
      conditioned medium can suppress sodium L-ascorbate- induced apoptosis of B16F10
      cells, and the ingredients with relative molecular mass less than 5 000 are
      responsible for this effect.

PMID- 22381746
TI  - [Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in
      rats by up-regulating heme oxygenase-1 expression].
AB  - OBJECTIVE: To study the effect of genistein on the expression of heme oxygenase-1
      (HO-1) in rats with pulmonary arterial hypertension (PAH) induced by
      monocrotaline (MCT). METHODS: Sixty male Sprague-Dawley rats were randomly
      divided into 4 groups (n=15), namely the control group, model group, low-dose (20
      ug/kg) genistein group and high-dose (80 ug/kg) genistein group. The hemodynamic
      parameters were measured and the remodeling of pulmonary small arteries was
      observed by electron microscope (EM). The expression of HO-1 in the lung tissues
      were detected by Western blotting. RESULTS: Compared with the model group,
      genistein treatment significantly reduced the elevated mean pulmonary arterial
      pressure, improved the right ventricular hypertrophy index, and increased the
      expression of HO-1 in a dose-dependent manner. CONCLUSION: Genistein attentuates
      pulmonary arterial hypertension in MCT-treated rats possibly by up-regulation of
      HO-1 in the lung tissues.

PMID- 22381747
TI  - [Apoptosis and proliferation of corpus cavernosum smooth muscle cells in diabetic
      rats].
AB  - OBJECTIVE: To explore the characteristics of cell apoptosis and proliferation of
      corpus cavernosum smooth muscle (CCSM) cells in diabetic rats. METHODS: From a SD
      rat model of diabetes induced by a single dose of streptozotocin, CCSM cells were
      isolated for primary culture and identified using immunocytochemical assays for
      SMalpha-actin. The proliferation of CCSM cells was evaluated by WST-1 assay, and
      flow cytometry was used to detect the cells apoptosis. Real-time fluorescence
      quantitative RT-PCR (qRT-PCR) was used to analyze the relative expression of
      proliferation cell nucleus antigen (PCNA) and caspase-3 mRNA. RESULTS: The
      proliferation rate of the primarily cultured CCSM cells from diabetic rats was
      significantly decreased and the apoptosis rate significantly increased compared
      with those of the cells from the control rats. The expression of PCNA mRNA was
      significantly lowered while caspase-3 mRNA significantly increased in the corpus
      cavernosum of the diabetic rats (P<0.001). CONCLUSION: In rats with persisted
      hyperglycemia, a higher apoptosis rate and a lower proliferation rate both
      contribute to the reduction of CCSM cells.

PMID- 22381748
TI  - [Effect of dibutyl phthalate and di-(2-ethylhexyl) phthalate on urine SOD
      activity and MDA content in rats].
AB  - OBJECTIVE: To evaluate the effect of dibutyl phthalate (DBP) and di-(2
      ethylhexyl) phthalate (DEHP) on urine superoxide dismutase (SOD) activity and
      malondialdehyde (MDA) content in rats. METHODS: According to 2*2 factorial
      analysis, 60 adult male SD rats were randomized into 10 groups (n=6), including a
      control group (fed with sesame oil), 3 DBP groups (fed with DBP at the doses of
      30, 100 and 300 mg/kg), 3 DEHP groups (with DEHP at 50, 150, and 450 mg/kg), and
      3 DBP+DEHP groups (with 30 mg/kg DBP+50 mg/kg DEHP, 100 mg/kg DBP+150 mg/kg DEHP,
      and 300 mg/kg DBP +450 mg/kg DEHP). The agents were administered in a single dose
      through gavage in a volume of  2 ml. After the treatments, the 24, 48, 72, and 96
      h urine samples were collected to determine the SOD activity and MDA content.
      RESULTS: DBP and DEHP, either alone or in combination, significantly decreased
      SOD activity and increased MDA content in the urine collected at 24 h but not at
      the other time points. Such changes were gradually reversed with time.
      CONCLUSION: DBP or DEHP treatment alone can result in significant oxidative
      damage in the kidney of rats, and the toxic effect of the combined exposure is
      even more obvious.

PMID- 22381749
TI  - [Lentivirus-mediated LOX-1-RNA interference attenuates oxidative stress-induced
      apoptosis in myocardial cells].
AB  - OBJECTIVE: To construct a lectin-like oxidized low-density lipoprotein receptor
      (LOX-1) RNA interference (RNAi) lentivirus and explore the role of LOX-1 in
      H(2)O(2)-induced apoptosis of rat myocardial cells. METHODS: LOX-1 shRNA sequence
      was synthesized and cloned into pLentiLox3.7 (pLL3.7) lentiviral vector to
      construct the lentiviral vector pLL3.7-LOX1. The lentiviral vectors (pLL3.7 and
      pLL3.7-LOX1) and the packaging vectors dR8.9 and VSVG were co-transfected into
      293FT cells for packaging the lentivirus. H9C2 myocardial cells were infected by
      the lentiviruses to observe the inhibitory rate of LOX-1 on H(2)O(2)-induced
      apoptosis of H9C2 cells by RT-PCR, CCK-8, and Hochest33258 staining. RESULTS:
      Double restriction enzyme digestion and DNA sequencing confirmed correct
      insertion of the sequence. Suppression of LOX-1 by the lentivirus attenuated
      H(2)O(2)-induced cell viability reduction and apoptosis in the myocardial cells
      (P<0.01). CONCLUSION: LOX-1 activation may play an important role in H(2)O(2)
      induced apoptosis of rat myocardial cells.

PMID- 22381750
TI  - [Fungal infection induced by Cryptococcus neoformans aerosol inhalation in
      immunosuppressed Balb/c mice].
AB  - OBJECTIVE: To explore the feasibility of inducing fungal infection by
      Cryptococcus neoformans aerosol inhalation in immunosuppressed Balb/c mice.
      METHODS: Twenty-four Balb/c mice were randomized into cyclophosphamide (CTX)
      group and control group (n=12). The mice in CTX group were subject to inhalation
      of Cryptococcus neoformans aerosol prepared using a ultrasonic nebulizer 4 days
      after intraperitoneal CTX injection, and the control mice received the inhalation
      only. The leukocyte count and changes in appetite, body weight, and behaviors of
      the mice were observed after the treatments. On days 3 and 7 after the
      inoculation, the mice were sacrificed to analyze the fungal counts in brain and
      lung tissue homogenates and examine the pulmonary pathologies. RESULTS: CTX
      injection caused lowered appetite and body weight loss in the mice, and
      significantly reduced the leukocyte counts (2.77?0.45 vs 8.26?0.56, P<0.05). At
      days 3 and 7 after inoculation, the Cryptococci load in the lungs increased
      obviously in CTX group with a colony-forming unit (CFU) of the lungs of
      271.67?122.22 and 41.67?0.28, respectively, significantly higher than that in the
      control group (60.00?43.36 and 3.00?5.30, respectively, P<0.05). In CTX group,
      the CFU was 10.17?5.42 and 9.17?6.34 in the peripheral blood and 6.83?4.92 and
      11.00?5.44 in the brain tissue at days 3 and 7, respectively, whereas no
      Cryptococci was detected in the peripheral blood or in the brain tissue in the
      control group. Pathological examination of the lungs revealed destruction of
      normal alveolar structure in CTX group, with numerous infiltrating inflammatory
      cells and visible yeast. CONCLUSION: Inhalation of Cryptococcus neoformans
      aerosol can cause fungal infection in the lungs of immunosuppressed Balb/c mice.

PMID- 22381751
TI  - [Epithelial to mesenchymal phenotype transition in the liver of rats with bile
      duct ligation].
AB  - OBJECTIVE: To investigate the occurrence of epithelial to mesenchymal phenotype
      transition (EMT) in the liver of rats following bile duct ligation (BDL).
      METHODS: Twenty-four male Wistar rats were randomized into sham-operated group
      and BDL group. Liver fibrosis of the rats was evaluated by HE staining and
      Masson's trichrome staining. Western blotting was used to detect the expression
      levels of the epithelial markers albumin and E-cadherin and the mesenchymal
      markers type I collagen and vimentin in the liver tissue. Immunofluorescence was
      employed to determine the co-localizations of FSP-1+vimentin, FSP-1+type I
      collagen, FSP-1+albumin, and albumin+type I collagen in cells. RESULTS: Compared
      with those in sham-operated group, the rats in BDL group showed significantly
      increased ISHAK fibrosis score (4.42+1.16 vs 0, P+0.000), METAVIR fibrosis score
      (3.42+0.67 vs 0, P+0.000) and type I collagen levels (0.30+0.06 vs 0.11+0.07,
      P+0.000) with up-regulated protein levels of albumin (0.53+0.63 vs 1.12+0.01,
      P+0.000) and E-cadherin (0.21+0.01 vs 0.44+0.01, P+0.000) and down-regulated type
      I collagen (8.21+0.12 vs 0.24+0.01, P+0.000) and vimentin (3.14+0.01 vs
      0.37+0.01, P+0.000). The number of cells with co-localizations of FSP-1+vimentin,
      FSP-1+type I collagen, FSP-1+albumin, and albumin+type I collagen was also
      significantly increased in BDL group. CONCLUSION: BDL causes significantly
      decreased expression of epithelial markers and increased expressions of the
      mesenchymal markers in rats, indicating the occurrence of EMT in some of the
      liver cells.

PMID- 22381752
TI  - [Design, synthesis and characterization of cyanopyrrolidine-bearing compounds as
      DPP-4 inhibitors].
AB  - OBJECTIVE: To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl
      peptidase 4 (DPP4) inhibitors and characterize their biological activities in
      vitro. METHODS: Eleven analogues of carbonitrilpyrrolidine were designed and
      synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl
      bromide with substituted phenyl piperazine pyridazinones. RESULTS: The structures
      of the compounds were characterized by (1)H-NMR and MS spectra. Biological
      evaluation indicated that most of the compounds exhibited moderate inhibitory
      activities against DPP4. CONCLUSION: The preliminary bioassay indicates that all
      the synthesized compounds have moderate DPP-4 inhibition activity, especially the
      compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the
      concentration of 1*10(5) nmol/L, respectively.

PMID- 22381753
TI  - [Effects of Sanren decoction on Th1/Th2 cytokines in rats with spleen-stomach
      damp-heat syndrome].
AB  - OBJECTIVE: To investigate the effects of Sanren decoction on the immune function
      of rats with spleen-stomach damp-heat (DHSS) syndrome. METHODS: Fifty  male SD
      rats were randomly allocated into normal control group, DHSS model group, and 3
      Sanren decoction groups (high, medium and low doses). The effects of the
      decoction on the body mass, rectal temperature (RT), water and food intake,
      histopathological changes of the gastrointestinal mucosa and serum levels of
      interleukin (IL)-4 and interferon (IFN)-gamma were evaluated. RESULTS: The serum
      levels of IFN-gamma and IL-4 in the model group significantly increased compared
      with those in the control group (P<0.01), with a slightly increased IFN-gamma/IL
      4 ratio (P>0.05). Sanren decoction obviously reduced the rectal temperature and
      significantly decreased the production of both cytokines. High-dose Sanren
      decoction caused more markedly decreased IL-4 level (P<0.05) to result in a
      significantly increased IFN-gamma/IL-4 ratio (P<0.05). CONCLUSIONS: A shift of
      Th1/Th2 balance toward Th1 immune response is demonstrated in rats with DHSS
      syndrome, and Sanren decoction produces a protective effect on the
      gastrointestinal mucosa by immunoregulation.

PMID- 22381754
TI  - [Construction of a prokaryotic expression vector of human tau multi-epitope
      peptide and immunogenicity of the expressed product].
AB  - OBJECTIVE: To construct a prokaryotic expression vector of human tau multiepitope
      peptide for examining the immunogenicity of a TauP1/P2 DNA vaccine in mice using
      the expressed product. METHODS: The coding sequence of Tau multiepitope peptide
      gene was amplified from the plasmid pVAX1-Tau by PCR and inserted into the
      prokaryotic expression vector pGEX-4T-2 to construct the recombinant plasmid pGEX
      4T-2-TauP1/P2. The positive recombinants were transformed into E.coli BL21 cells,
      and the expression of fusion protein GST-TauP1/P2 was induced by IPTG and
      identified by SDS-PAGE. Mice was immunized with TauP1/P2 DNA vaccine and the
      production of the specific antibodies was detected by Dot-blot analysis using the
      purified fusion protein. RESULTS: A gene fragment 300 bp in length was amplified.
      Enzyme digestion and DNA sequencing verified correct construction of the
      prokaryotic expression plasmid pGEX-4T-2-TauP1/P2. The expression of target
      fusion protein GST-TauP1/P2 was detected by SDS-PAGE. Specific antibodies against
      TauP1/P2 were detected in the serum of mice immunized with the DNA vaccine using
      GST-TauP1/P2 fusion protein. CONCLUSION: The constructed prokaryotic expression
      plasmid of human Tau multiepitope peptide is capable of expressing the target
      fusion protein, which specifically recognizes the specific antibodies against
      TauP1/P2 in mice immunized with TauP1/P2 DNA vaccine.

PMID- 22381755
TI  - [Effect of sodium butyrate on apoptosis and stromal interaction molecule and
      Orai1 activity in human colon cancer HCT-116 cells in vitro].
AB  - OBJECTIVE: To investigate the mechanism underlying sodium butyrate (NaB)-induced
      apoptosis of a human colon cancer cell line HCT-116. METHODS: The apoptosis of
      HCT-116 cells induced by NaB was confirmed by hoechst33342 staining and AnnexinV+
      PI assay. The changes in the intracellular localization of stromal interaction
      molecule (STIM1) and Orai1 following NaB treatment were detected by
      immunofluorescence technique. Western blotting was used to investigate the
      protein expression levels of STIM1 and Orai1. RESULTS: NaB induced apoptosis and
      caused translocation and colocalization of STIM1 and Orai1 in HCT-116 cells.
      CONCLUSION: The apoptosis of human colon cancer cells induced by NaB is
      correlated to the redistribution of STIM1 and Orai1.

PMID- 22381756
TI  - [Independent correlations of cerebral microstructural changes on DTI to general
      cognitive function and executive function in patients with subcortical ischemic
      vascular disease].
AB  - OBJECTIVE: To investigate whether DTI abnormalities in patients with nondemented
      subcortical ischemic vascular disease (SIVD) are correlated to general cognitive
      function and executive function independent of conventional MRI parameters.
      METHODS: Sixty-six SIVD patients including 30 with cognitive impairment without
      dementia (VCIND) and 36 with normal cognition (NCI) underwent DTI and cognitive
      assessment of the general cognitive function and executive function. Conventional
      MRI parameters and DTI parameters were measured within the white matter lesions
      (WMLs), normal-appearing white matter (NAWM) and normal-appearing gray matter
      (NAGM). The independent predictors of general cognitive function and executive
      function in SIVD patients was analyzed. RESULTS: NCI and VCIND patients showed
      significant differences in the periventricular WMLs, ADC valus in NAWM and WMLs
      of the centrum semiovale, and FA values in NAWM of the anterior periventricular.
      Except for ADC values of the caudate nucleus, ADC and FA values in the
      subcortical NAGM showed significant difference between the two groups. After
      controlling for age and education, PVLs and ADC values in the WMLs and NAWM of
      the centrum semiovale and putamen, and FA values in the anterior periventricular
      NAWM, WMLs and putamen showed significant correlations to MMSE; the number of
      lacunar infarcts, ADC values in posterior periventricular NAWM and caudate
      nucleus, and FA values in anterior periventricular NAWM and thalamus showed
      significant correlations to CDT. Multivariate analysis showed independent
      correlations of the ADC values in WMLs and NAWM of the centrum semiovale to MMSE,
      and demonstarted correlations of the ADC values of the caudate nucleus and number
      of lacunar infarcts to CDT. CONCLUSION: In nondemented SIVD subjects, the
      integrity of the white matter in the centrum semiovale strongly correlates to the
      general cognition, and the microstructural damage of the caudate nucleus head
      predicts executive function impairment independent of other MRI variables.

PMID- 22381757
TI  - [Expression of hsa-miR-20a in human glioma tissues and its effect on the
      proliferation of human glioma cells in vitro].
AB  - OBJECTIVE: To investigate miR-20a expression in human glioma and normal brain
      tissues and its effect on the proliferation of glioma cells in vitro. METHODS:
      The expression of miR-20a was detected in human normal brain tissues and glioma
      tissues by real-time RT-PCR. miR-20a mimics were synthesized and transfected into
      U251 cells via liposome, and the cell proliferation were detected using MTT assay
      and flow cytometry. RESULTS: The glioma tissues showed significantly up-regulated
      expression of miR-20a compared with normal brain tissues (P=0.035). The
      expression level of miR-20a was higher in high-grade than in low-grade gliomas.
      miR-20a mimics significantly enhanced the proliferation of U251 cells and the
      percentage of S-phase cells. CONCLUSION: miR-20a shows potent effect in promoting
      the growth of glioma cells, suggesting its important role in the pathogenesis of
      human glioma.

PMID- 22381758
TI  - [Effect of atorvastatin on cardiac function and TGF-beta1 signaling pathway after
      acute myocardial infarction in rats].
AB  - OBJECTIVE: To investigate the effect of atorvastatin on cardiac remodeling and
      function after acute myocardial infarction (AMI) in rats and whether this effect
      is mediated by transforming growth factor-beta1 (TGF-beta1) signaling pathway.
      METHODS: AMI was induced by left coronary artery ligation in 64 male Sprague
      Dawley rats, and 45 surviving rats were randomized into control group (n=15), low
      dose atorvastatin group (10 mg/kg, n=15) and high-dose atorvastatin group (20
      mg/kg, n=15). Similar surgical procedure was performed in sham-operated rats
      (n=15) without coronary ligation. Atorvastatin was given daily by gavage from the
      first day after AMI. Eight weeks later, the cardiac function, left ventricular
      weight/body mass index (LVMI), collagen volume fraction (CVF), and the
      expressions of TGF-beta1 and Smad2 were compared between the groups. RESULTS: AMI
      caused significantly reduced cardiac function, increased LVMI and CVF, and
      upregulated expressions of TGF-beta1 and Smad2 mRNA and proteins in the control
      group (P<0.05). The cardiac function, LVMI, and CVF were improved by
      atorvastatin, which also down-regulated the expressions of TGF-beta1 and Smad2
      (P<0.05), and the effects were more prominent in high-dose atorvastatin group
      (P<0.05). CONCLUSION: Atorvastatin can dose-dependently improve cardiac
      remodeling and function after AMI in rats, which is mediated by regulating the
      activity of TGF-beta1/Smad2 signaling pathway.

PMID- 22381759
TI  - [Effect of small interfering RNA targeting p63 on the proliferation and
      invasiveness of human cholangiocarcinoma cells in vitro].
AB  - OBJECTIVE: To construct a small interfering RNA (siRNA) vector targeting p63 and
      observe its effect on the proliferation and invasiveness of human
      cholangiocarcinoma cells in vitro. METHODS: Real-time PCR was used to examine the
      expression of p63 in human cholangiocarcinoma QBC939 cells. The recombinant
      lentivirus shRNA-p63 vector was constructed and transfected into QBC939 cells via
      Lipofectamine 2000 to establish a cholangiocarcinoma cell line with stable
      expression of siRNA-p63. The interfering efficiency of the siRNA targeting p63
      was assessed using Western blotting. MTT and soft agar colony formation assays
      were used to evaluate the changes in the cell proliferation, and Boyden test was
      employed to observe the cell invasiveness after the transfection. RESULTS: QBC939
      cells showed a high expression of p63. The recombinant lentivirus shRNA-p63
      vector was successfully constructed as verified by sequencing. Transfection with
      the vector significantly suppressed the proliferation and invasiveness of QBC939
      cells. CONCLUSION: Down-regulation of p63 can inhibit the proliferation and
      invasiveness of human cholangiocarcinoma QBC939 cells in vitro.

PMID- 22381760
TI  - [Perindopril and losartan attenuate intrahepatic Toll-like receptor 4 protein
      expression in rats with bile duct ligation-induced hepatic fibrosis].
AB  - OBJECTIVE: To investigate the expression of Toll-like receptor 4 (TLR4) in the
      liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and
      evaluate the inhibitory effects of perindopril and losartan on TLR4 expression.
      METHODS: Male Wistar Rats were randomly divided into sham-operated group (n=6),
      BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50
      mg/kg) (n=12). Perindopril and losartan groups were further divided into two
      subgroups for corresponding treatments by gastric lavage once daily for 14 and 30
      days. The protein level of TLR4 in the liver tissue was examined by Western
      blotting. RESULTS: In 14-day BDL group, the protein level of TLR4 significantly
      increased to 6.53?1.11 folds of that in the sham group (P<0.05), and was lowered
      significantly to 1.71?0.41 folds and 0.95?0.38 folds following perindopril and
      losartan treatments for 14 days. TLR4 expression significantly increased to
      6.51?0.87 folds and 5.64?0.87 folds of that of the sham group in perindopril and
      losartan groups after the 30-day treatments (P<0.05). CONCLUSION: TLR4 expression
      is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can
      be lowered by perindopril and losartan treatmemts for 14 days.

PMID- 22381761
TI  - [Effects of heat stress on Per2 mRNA expression in the liver of rats].
AB  - OBJECTIVE: To investigate the effect of acute heat stress on the day-night
      circadian gene Per2 mRNA expression in the liver of rats. METHODS: Male Wistar
      rats were randomly divided into two groups and exposed to heat at 32 degrees
      celsius; or to a room temperature at 24 degrees celsius; (control). After 7 days
      of heat exposure, the body temperature was measured by telemetry. The relative
      weight of the pituitary and adrenal glands was determined after the exposure, and
      liver Per2 mRNA expression level was detected using RT-PCR. RESULTS: Acute heat
      stress did not obviously affect body temperature or body weight of the rats.
      Seven days of heat exposure increased the relative weight of the pituitary and
      adrenal glands and significantly lowered Per2 mRNA expression level at night.
      CONCLUSION: Acute heat stress can interfere with the day-night circadian gene
      Per2 mRNA expression in rats.

PMID- 22381762
TI  - [Fertilization method for primary infertility patients without definite cause
      undergoing in vitro fertilization and embryo transfer].
AB  - OBJECTIVE: To determine the optimal fertilization method for primary infertility
      patients without definite causes undergoing in vitro fertilization and embryos
      transfer (IVF-ET). METHODS: A total of 321 IVF-ET cycles for primary infertility
      without definite causes were divided into two groups, namely group A with
      infertility period >= 5 years (165 cycles) and group B with infertility period <5
      years (156 cycles). Each group was further divided into IVF, ICSI, and partial
      ICSI subgroups. The fertilization rate, incidence of low fertilization rate and
      clinical pregnancy rate were analyzed. RESULTS: The fertilization rate of IVF in
      group A was 67.5%, significantly lower than that of ICSI and partial ICSI in the
      same group (82.0% and 77.7% respectively) and that in IVF control group (76.3%,
      P<0.05). The incidence of low fertilization rate of IVF in group A was 33.3%,
      significantly lower than that of ICSI and partial ICSI (8.3% and 15.8%, P<0.05);
      in group B, the incidence of low fertilization rate of IVF was 12.3%,
      significantly lower than that of IVF in group A but showed no significant
      differences from that of ICSI and partial ICSI in group B (P>0.05). In group A,
      IVF resulted in a significantly lower clinical pregnancy rate (21.1%) than ICSI
      (43.3%, P<0.05), half ICSI (40.0%, P<0.05), IVF in the control group (48%,
      P<0.05), and IVF in group B (50.0%, P<0.05). CONCLUSION: ICSI treatment can
      increase the fertilization rate in IVF-ET cycles in patients with primary
      infertility for unknown causes, and may improve the clinical outcome of patients
      with long infertility period.

PMID- 22381763
TI  - [Comparison of two mouse models of lung fibrosis induced by intratracheal
      instillation and intratracheal aerosol administration of bleomycin].
AB  - OBJECTIVE: To compare two methods of bleomycin administration for inducing lung
      fibrosis in mice. METHODS: Bleomycin (5 mg/kg) was intratracheally instilled or
      by intratracheal administration of its aerosol (100 ul) in mice. Evans Blue
      instead of bleomycin was intratracheally administered in the two manners to
      observe the liquid distribution in the lungs. On Days 14 after bleomycin
      treatment, the mice were sacrificed and the lungs were removed en bloc to
      determine the lung coefficient and hydroxyproline concentration, and the
      histological changes and lung fibrosis were evaluated by HE and Masson's
      trichrome staining, respectively. RESULTS: Evans Blue intratracheal aerosol
      distribution in the lung lobes. Intratracheal administration of bleomycin and its
      aerosol produced no obvious changes in the lung coefficient (P=0.434), and
      resulted in similar total histopathological scores and fibrosis level in mice
      (P=0.244 and 0.686, respectively). Bleomycin instillation caused obvious lung
      injury and lung fibrotic foci with significantly different histological and
      fibrotic scores between the pulmonary lobes (P=0.016 and 0.038, respectively),
      while bleomycin aerosol inhalation resulted in similar histological and fibrotic
      scores in the pulmonary lobes (P=0.466 and 0.29, respectively). A higher level of
      hydroxyproline was observed in mice with bleomycin aerosol administration
      (P=0.020). CONCLUSION: Intratracheal bleomycin instillation and bleomycin aerosol
      inhalation induce similar levels of fibrosis in the lungs of mice, but the latter
      causes more extensive and more evenly distributed fibrosis in the lungs.

PMID- 22381764
TI  - [Laparoendoscopic single-site retroperitoneal lymph node dissection: initial
      experience and 1-year follow-up].
AB  - OBJECTIVE: To summarize our initial experience with laparoendoscopic single-site
      (LESS) retroperitoneal lymph node dissection (RPLND) for treatment of
      nonseminomatous testicular cancer. METHODS: From September 2010 to June 2011, 3
      patients (aged 19-27 years) with right testicle enlargement and elevated alpha
      fetoprotein level underwent right radical orchidectomy. Histopathological
      analysis revealed nonseminomatous germ cell tumor. LESS-RPLND was performed 3
      weeks after orchiectomy. The homemade port was inserted through a 3-cm right
      pararectal incision in the right lower quadrant for unilateral RPLND using nerve
      sparing technique and modified right-sided template removal similar to those in
      open RPLND. RESULTS: The operation was successfully performed with a mean
      operative time of 240 min and a mean estimated blood loss of 50 ml. No conversion
      to open or conventional laparoscopic surgery was required. No major perioperative
      complications were observed. For the first case, the number of lymph nodes
      obtained for final histopathological examination was 11, and two positive nodes
      were detected. For the other 2 cases, no positive nodes were detected.
      Chemotherapy was administered in the first case. Alpha-fetoprotein level
      decreased close to the baseline one week postoperatively and no relapse occurred
      in these cases 3 month after RPLND.  Follow-up at 1 year after the surgery showed
      good tumor control and preservation of the sexual function. CONCLUSION: LESS
      RPLND is safe and feasible for treatment of nonseminomatous testicular cancer,
      and the pararectal incision provides an ideal surgical approach with good
      cosmetic result, but the long-term effect needs to be tested by further large
      population-based study.

PMID- 22381765
TI  - [Serum cortisol and peripheral blood mononuclear cell glucocorticoid receptor
      mRNA expression in severe alopecia areata with liver-kidney deficiency syndrome].
AB  - OBJECTIVE: To investigate serum cortisol level and glucocorticoid receptors (GR)
      mRNA expression in peripheral blood mononuclear cells (PBMCs) in patients with
      severe alopecia areata and liver-kidney deficiency syndrome and their involvement
      in the pathogenesis of severe alopecia areata. METHODS: In 32 patients with
      severe alopecia areata, serum cortisol levels were measured by chemiluminescence
      assay and GR mRNA expression in the PBMCs was detected using reverse
      transcription real-time fluorescence quantitative PCR before and after treatment,
      with 20 normal subjects serving as the controls. RESULTS: Serum cortisol level
      showed no significant difference between the cases and the normal controls
      (P>0.05). The expression of GR mRNA in the PBMCs was significantly lower in the
      patients than in the normal controls (P<0.05). The expression of GR mRNA was even
      lower after treatments in patients with alopecia areata (P<0.01). CONCLUSIONS: GC
      GR disorder exists in severe alopecia areata. A decreased GR mRNA expression in
      the PBMCs can be involved in the pathogenesis of severe alopecia areata, and such
      pathological changes at the receptor and genetic levels might also serve as the
      microscopic basis of liver-kidbey deficiency syndrome in severe alopecia areata.

PMID- 22381766
TI  - [High-throughput genotyping multiplex ligation-dependent probe amplification for
      assisting diagnosis in a case of anti-Di(a)-induced severe hemolytic disease of
      the newborn].
AB  - OBJECTIVE: To report a rare case of hemolytic disease of the newborn (HDN) with
      kernicterus caused by anti-Di(a) diagnosed using high-throughput genotyping
      multiplex ligation-dependent probe amplification (MLPA). METHODS: Conventional
      serological methods were used to detect the antibodies related with HDN. The
      genotypes of more than 40 red blood cell antigens for the newborn and her parents
      were obtained using the high-throughput MLPA assay. The antibody titers were
      tested using a standard serological method. RESULTS: The unknown antibody against
      the low-frequency antigens was predicted based on the primary serological tests.
      The genotyping results for more than 40 red blood cell antigens of the newborn
      and her parents showed incompatible antigens of MNS and Diego blood group system,
      indicating the existence of anti-N or anti-Di(a). Further serological tests
      confirmed anti-Di(a) existence in the plasma of the newborn and her mother. The
      titer of anti-Di(a) in the mother's plasma was 1:32. CONCLUSION: Severe HDN
      including kernicterus can result from anti-Di(a). High-throughput genotyping MLPA
      assay can help type some rare antigens in complicated cases. The reagent red cell
      panels including Di(a)-positive cells are necessary in routine antibody screening
      test in Chinese population.

PMID- 22381767
TI  - [Effect of C-reactive protein on Notch pathway components in human periphery
      blood endothelial progenitor cells].
AB  - OBJECTIVE: To observe the effect of C-reactive protein (CRP) on the expressions
      of Notch pathway components in human peripheral blood endothelial progenitor
      cells (EPC) in vitro. METHODS: Mononuclear cells isolated by density gradient
      centrifugation of human peripheral blood mixed with 6% hydroxyethyl starch (Hes)
      were plated on fibronectin-coated 6-well culture dishes. After 7 days, the
      adherent cells were cultured in the presence of 10 and 20 mg/L CRP for 48 h, and
      the proliferation, migration, and adhesion abilities of the cells were observed.
      The mRNA expressions of Notch-1 and its ligand Jagged-1 in the EPCs were measured
      by RT-PCR, and their protein expressions by Western blotting. RESULTS: CRP at 10
      and 20 mg/L caused a significant reduction in the number of viable EPCs (61?3 and
      54?3, respectively) as compared with PBS (71?4, P<0.05). CRP also resulted in a
      significant suppression of the proliferation, migration and adhesion capacities
      of the EPCs. The mRNA and protein expressions of Jagged-1 and Notch-1 in the EPCs
      significantly increased following CRP exposure in comparison with PBS treatment.
      CONCLUSION: CRP can suppress the proliferation, migration and adhesion capacities
      of the EPCs probably by affecting the expressions of the Notch-1 pathway
      components.

PMID- 22381768
TI  - [Targeted injection of ozone through the posterior approach via the spinal canal
      and dural sac for treating lumbar disc herniation].
AB  - OBJECTIVE: To evaluate the effect of targeted percutaneous injection of medical
      ozone through the posterior approach via the spinal canal and dural sac under CT
      guidance for treatment of lumbar disc herniation. METHODS: In 262 patients with
      lumbar disc herniation, medical ozone was injected percutaneously under CT
      guidance into the lumbar intervertebral disc by the posterior approach at
      paramedian 1-2 cm from the spinous process, targeting the affected lumbar discs,
      protruded nucleus pulposus and ipsilateral lateral recess. The concentration of
      ozone was 40-50 ug/ml in the disc/protruded nucleus pulposus and 30 ug/ml in the
      lateral recess (around the nerve root). RESULTS: The treatment procedures were
      successfully completed in all the 262 patients. The average scores of JOA and VAS
      before treatment were 8.30?1.4 and 8.73?0.8, and changed significantly to
      24.16?3.2 (P=0.0158) and 2.41?0.2 (P=0.0242) after treatment, respectively.
      According to the modified MacNab criteria, the therapeutic effect was excellent
      in 165 cases, fair in 64 cases, acceptable in 20 cases, and poor in 13 cases,
      with a total success rate of 87.4%. No patient showed serious complications after
      the treatment. CONCLUSION: Compared with routine ozone therapy by the posterior
      lateral approach, targeted percutaneous ozone injection into the intervertebral
      disc by the modified posterior approach is safe and yields better therapeutic
      effect for lumbar disc herniation.

PMID- 22381769
TI  - [Establishment of a porcine model of biliary leakage with laparoscopy].
AB  - OBJECTIVE: To establish a animal model of biliary leakage in pigs with
      laparoscopy. METHODS: Eight healthy Bama minipigs were subject to laparoscopic
      surgery under general anesthesia.The cystic duct was resected at 0.5-1.0 cm from
      the root and the stump was left open with the gallbladder removed. Blood routine
      and hepatic functions of the pigs were tested before and 24 h after the surgery,
      and endoscopic retrograde cholangiography (ERC) was performed 24 h after the
      surgery. At 48 h after the surgery, the pigs were sacrificed for observation of
      the stump of the cystic duct. RESULTS: The gallbladder, cystic duct, cystic
      artery, and the anatomical relations between the gallbladder and liver and
      between the cystic duct and common bile duct were fully exposed under
      laparoscopy. White blood cells, neutrophils and direct bilirubin increased
      significantly after the operation (P<0.05). The cystic ducts were resected at 0.5
      1 cm away from the roots of the cystic ducts in 7 pigs and at 2 cm in 1 pig.
      CONCLUSION: Laparoscopy is safe and feasible for establishing the porcine model
      of biliary leakage.

PMID- 22381770
TI  - [Outcomes of in vitro fertilization-embryo transfer and intracytoplasmic sperm
      injection for non-male infertility patients with a low number of oocytes
      retrieved].
AB  - OBJECTIVE: To compare the outcomes of in vitro fertilization-embryo transfer
      (IVF) and intracytoplasmic sperm injection (ICSI) in non-male infertility
      patients with a low number of oocytes retrieved and provide evidences for
      defining the indications of ICSI. METHODS: A retrospective analysis was conducted
      among 220 non-male infertility patients with a low number of oocyte
      retrieved(<=5) including 151 receiving IVF and 69 undergoing ICSI. The baseline
      characteristics, ovary response index, fertilization results, embryo quality and
      clinical outcomes were compared between the 2 groups. RESULTS: Although the
      fertilization rates, normal fertilization rates, complete fertilization failure
      rates, cleavage rates, good embryo rates, implantation rates and clinical
      pregnancy rates showed no significant differences between the 2 groups, the
      complete fertilization failure rates tended to decrease and the other indices
      tended to increase in IVF group. CONCLUSIONS: ICSI can not improve the
      fertilization results, embryonic development potential or clinical outcomes in
      non-male infertility patients with a low number of oocytes retrieved, and is
      therefore not recommended for these patients.

PMID- 22381771
TI  - [Comparison of two regimens of postoperative concurrent chemoradiotherapy in
      adult patients with grade III-IV cerebral gliomas].
AB  - OBJECTIVE: To compare the therapeutic efficacy of two regimens of postoperative
      radiotherapy with concurrent chemotherapy using temozolomide (TMZ) and teniposide
      (VM-26) plus semustine (Me-CCNU) in adult patients with grade III-IV cerebral
      gliomas. METHODS: Ninety-six adult postoperative patients with grade III-IV
      cerebral gliomas were randomized into two groups (n=48) to receive 60 Gy
      radiotherapy with concurrent TMZ treatment (TMZ-RT group) and radiotherapy with
      VM-26 plus Me-CCNU treatments (VM-RT group). The adverse effects of marrow
      depression, gastrointestinal toxicity and acute radiation-induced brain injury
      were observed. The immediate effect and survival outcome of the patients were
      compared between the two groups. RESULTS: No adverse effects beyond grade III
      were observed in the two groups. TMZ-RT group showed a significantly lower
      incidence of grade I-II adverse effects than VM-RT group (P<0.05). The median
      survival time and 1-, 2-, and 3-year survival rates of the patients in TMZ-RT
      group were 28 months, 72.9%, 54.2% and 31.3%, respectively, showing significant
      differences from those in VM-RT group (16 months, 62.5%, 33.3% and 16.7%,
      respectively, P<0.05). CONCLUSION: Radiotherapy with concurrent TMZ chemotherapy
      is an effective regimen with mild toxicities for treatment of adult malignant
      cerebral glioma.

PMID- 22381772
TI  - [Surgical treatment of congenital bicuspid aortic valve in 73 patients aged over
      50 years].
AB  - OBJECTIVE: To summarize the clinical characteristics, surgical management and
      postoperative complications in patients with congenital bicuspid aortic valve
      (CBAV) over 50 years of age. METHODS: From January 2009 to September 2011, 73
      CBAV patients aged 51-76 years (mean 61.8?0.73 years) were treated in our center.
      Except for 1 patient who underwent Bentall surgery and another having Wheat
      surgery, all the patients received aortic valve replacement (AVR), including 7
      with double (mitral and aortic) valve replacement (DVR), 6 with mitral valvular
      plasty, 11 with tricuspid valvular plasty, 8 with coronary artery bypass graft
      implantation, 1 with aortic-left ventricular tunnel repair, 1 with atrial maze
      ablation, and 1 with left atrial thrombosis removal. RESULTS: Two patients died
      after the surgery, with a perioperative mortality rate of 2.7%. The
      cardiopulmonary bypass time was 78-217 min (mean 131.9 ?6.0 min) with an aortic
      blocking time of 56-158 min (mean 88.2 ?4.8 min) and total postoperative ICU time
      of 23.0-647.4 h (mean 97.9?10.5 h). The postoperative complications included low
      heart output syndrome in 5 cases, bleeding in 4 cases, wound debridement in 4
      cases, and hemodialysis due to acute renal failure in 1 case. The left
      ventricular end diastolic diameter reduced significantly after the surgery
      (52.6?1.7 vs 43.2?1.0, P=0.001). No significant changes were detected in the left
      ventricular ejection fraction (62.3?2.5 vs 65.5?1.3, P=0.257). CONCLUSION:
      Thorough preoperative examination, preoperative risk factor assessment, timely
      perioperative interventions, careful evaluation of patients' tolerance of
      surgery, and prevention of surgical complications are essential to decrease the
      perioperative mortality in elderly patients with CBAV.

PMID- 22381773
TI  - [Predictors of the no-reflow phenomenon after primary percutaneous coronary
      intervention for acute myocardial infarction].
AB  - OBJECTIVE: To identify the risk factors for no-reflow (NR) phenomenon after
      primary percutaneous coronary intervention (PCI) in patients with acute
      myocardial infarction. METHODS: A total of 843 patients with AMI underwent
      primary PCI within 12 h following onset of the ischemic symptoms. According to
      TIMI flow grade and myocardial blush grade, the patients were divided into reflow
      group and NR group after primary PCI, and the clinical data, angiography findings
      and surgical data were compared to analyze the factors contributing to NR.
      RESULTS: NR occurred in 15.9% of the AMI patients after primary PCI. Univariate
      analysis showed that previous myocardial infarction, Killip classes of MI, time
      to reperfusion, IABP use before PCI, TIMI flow grade before primary PCI, long
      target lesion, pre-PCI thrombus score and method of reperfusion were correlated
      to NR (P<0.05 ). Multiple logistic analysis identified the time to reperfusion
      (OR=1.60; 95% CI: 1.02-2.73), TIMI flow grade before primary PCI (OR=1.1; 95% CI:
      1.04-1.16), long target lesion (OR=1.40; 95% CI: 1.19-1.69), and pre-PCI thrombus
      score (OR=2.02; 95% CI: 1.47-2.76) as the independent predictors of NR after
      primary PCI. CONCLUSION: The time to reperfusion, TIMI flow grade before primary
      PCI, long target lesion, and pre-PCI thrombus score are independent predictors of
      NR after primary PCI for AMI.

PMID- 22381774
TI  - [Role of centromere protein H in human gastric cancer cell proliferation].
AB  - OBJECTIVE: To explore the role of centromere protein H (CENP-H) in the
      proliferation of human gastric cancer cells. METHODS: RT-PCR and Western blot
      analysis were employed to examine the mRNA and protein expressions of CENP-H in 7
      human gastric cancer cell lines and immortalized human gastric epithelial cells
      (GES-1). The cells were infected with the retrovirus vectors pMSCV-CENP-H or CENP
      H-RNAi to establish stable cell lines with high CENP-H expression or CENP-H
      expression interference. MTT assay and colony formation assay were used to
      examine the changes in the cell proliferation after the infection. RESULTS: CENP
      H was over-expressed in gastric cancer cell lines AGS, BGC823, SGC-7901, MKN45,
      HGC27, MGC-803 and MKN28 at both mRNA and protein levels. The established
      AGS/CENP-H cell line with increased CENP-H expression showed enhanced
      proliferative activity, while the cell line MGC-803/CENP-H-RNAi with CENP-H
      expression interference showed an obviously lowered proliferation ability.
      CONCLUSION: CENP-H promotes the proliferation of human gastric cancer cells,
      suggesting its important role in the occurrence and development of gastric
      cancer.

PMID- 22381775
TI  - [MiRNA-146a promotes proliferation and migration of rat vascular smooth muscle
      cells in vitro in a nuclear factor-kappaB-dependent manner].
AB  - OBJECTIVE: [corrected] To understand the role of miRNA-146a in the proliferation
      and migration of primarily cultured rat vascular smooth muscle cells (VSMCs) and
      investigate the mechanisms. METHODS: Primarily cultured rat VSMCs were
      transfected with a synthesized miRNA-146 inhibitor, a scramble sequence or PBS
      via Lipofectamine2000. Cell counting kit 8 (CCK8) and transwell assay were
      employed to assess the proliferation and migration of the transfected cells, and
      the expressions of nuclear factor-kappaB p65 (NF-kappaBp65) and proliferation
      cell nuclear antigen (PCNA) were detected using Western blotting. RESULTS: A 48-h
      transfection of the VSMCs with miRNA-146 inhibitor caused significantly lowered
      miRNA-146a expression as compared with that in VSMCs transfected with the
      scramble sequence or PBS (P<0.01), resulting also in lowered proliferative and
      migration ability of the cells (P<0.01). The expression levels of NF-kappaBp65
      and PCNA were remarkably lower in cells transfected with miRNA-146 inhibitor than
      in the cells in the other two groups (P<0.05). CONCLUSION: miRNA-146a is capable
      of promoting the proliferation and migration of rat VMSCs probably by enhancing
      the expression of NF-kappaBp65.

PMID- 22381776
TI  - [Single-port laparoscopic surgery for radical nephrectomy: report of 22 cases].
AB  - OBJECTIVE: [corrected] To evaluate the method and technique of single-port
      laparoscopic radical nephrectomy. METHODS: Form January 2009 to September 2011,
      22 patients with renal carcinoma were treated with single-port laparoscopic
      radical nephrectomy. An incision about 5 cm in length was made through the
      umbilicus or in the postaxillary line under the 12th rib to establish the
      peritoneal or retroperitoneal working space. A single-port cannulation was
      deployed and the operation was carried out using standard and crooked
      laparoscopic equipment. RESULTS: The operations were completed successfully in
      all the 22 cases without conversion to open surgery, but additional trocar was
      needed in 5 cases. The mean operative time of radical nephrectomy was 150 min (90
      240 min). The mean postoperative hospital stay was 7.6 days (3-15 days). The
      operation left a roughly 5-cm-long scar in all the cases. CONCLUSION: Single-port
      laparoscopic radical nephrectomy is safe and feasible with good cosmetic effect
      and shows much potential in radical resection of renal carcinoma.

PMID- 22381777
TI  - [Clinical application of DNA sequencing for detecting point mutations in
      hepatitis B virus associated with drug resistance].
AB  - OBJECTIVE: [corrected] To assess the specificity and applicability of direct PCR
      sequencing in the detection of point mutations in hepatitis B virus (HBV)
      associated with drug resistance. METHODS: Serum samples were obtained from 120
      patients with hepatitis B treated with nucleoside analogus for at least 2 years
      to detect the point mutations in HBV genome in association with drug resistance
      using nested PCR and direct DNA sequencing. RESULTS: Forty out of the 120
      patients were found to have one or two point mutations associated with drug
      resistance, including 17 with L180M and M204V/I mutations (42.5%), 10 with
      M204V/I mutation (25%), 8 with N236T mutation (20%), 3 with L180M mutation
      (7.5%), and 1 with both A181V/T and N236T mutations (2.5%), and 1 with A181V/T
      mutation(2.5%). CONCLUSION: DNA sequencing is a good method to detect all known
      point mutations associated with HBV drug resistance.

PMID- 22381778
TI  - [Decitabine for treatment of myelodysplastic syndrome in an elderly patient and
      review of literature].
AB  - Findings in epigenetic changes in meylodysplastic syndromes (MDS) and the
      development of demethylating drugs provide a new approach to the treatment of
      MDS. We used standard-dose decitabine for treatment of MDS in an elderly patient
      with an International Prostate Symptom Score (IPSS) of moderate risk group 2, and
      achieved a complete response in the first course. We report our experience with
      this case and review the relevant literatures.

PMID- 22381779
TI  - RGD conjugates of the H2dedpa scaffold: synthesis, labeling and imaging with
      68Ga.
AB  - INTRODUCTION: The rekindled interest in the (68)Ga generator as an attractive
      positron emission tomography generator system has led us and others to
      investigate novel chelate systems for (68)Ga. We have previously reported our
      findings with the acyclic, rapidly coordinating chelate H(2)dedpa and its model
      derivatives. METHODS: In this report, we describe the synthesis of the
      corresponding bifunctional chelate scaffolds (H(2)dp-bb-NCS and H(2)dp-N-NCS) as
      well as the radiolabeling properties, transferrin stability, binding to the
      target using in vitro cell models and in vivo behavior the corresponding
      conjugates with the alpha(v)beta(3) targeting cyclic pentapeptide cRGDyK
      (monomeric H(2)RGD-1 and dimeric H(2)RGD-2). RESULTS: The ability of the
      conjugated ligands to coordinate Ga isotopes within 10 min at room temperature at
      concentrations of 1 nmol was confirmed. Complex [(67)Ga(RGD-1)](+) was more
      stable (92% after 2 h) than [(67)Ga(RGD-2)](+) (73% after 2 h) in a transferrin
      challenge experiment. IC(50) values for both conjugates (H(2)RGD-1 and H(2)RGD-2)
      and nonconjugated RGD were determined in a cell-based competitive binding assay
      with (125)I-echistatin using U87MG cells, where enhanced specific binding was
      observed for the multivalent H(2)RGD-2 conjugate compared to the monovalent
      H(2)RGD-1 and nonconjugated cRGDyK. The U87MG cell line was also used to generate
      subcutaneous xenograft tumors on RAG2M mice, which were used to evaluate the in
      vivo properties of [(68)Ga(RGD-1)](+) and [(68)Ga(RGD-2)](+). After 2 h of
      dynamic imaging, both block and nonblock mice were sacrificed to collect select
      organs at the 2-h time point. Although the uptake is specific, as judged from the
      ratios of nonblock to block (2.36 with [(67)Ga(RGD-1)](+), 1.46 with [(67)Ga(RGD
      2)](+)), both conjugates display high uptake in blood. CONCLUSIONS: We have
      successfully synthesized and applied the first bifunctional versions of H(2)dedpa
      for conjugation to a targeting vector and subsequent imaging of the corresponding
      conjugates.

PMID- 22381780
TI  - 11C-5-hydroxytryptophan positron emission tomography after radiofrequency
      ablation of neuroendocrine tumor liver metastases.
AB  - AIM: The aim was to assess the feasibility of (11)C-5-hydroxy-tryptophan positron
      emission tomography ((11)C-5-HTP-PET) in the follow-up after radiofrequency
      ablation (RFA) of liver metastases from neuroendocrine tumors (NETs). BACKGROUND:
      Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound
      (CEUS) are commonly used to evaluate the liver after RFA of NETs. In general,
      (11)C-5-HTP-PET is more sensitive in the visualization of NETs, but no studies
      have investigated its role after RFA. METHODS: Six consecutive patients with
      liver metastases from NETs were subjected to RFA treatment. All patients
      underwent baseline imaging before RFA and on two occasions (1-2 and 6-11 months)
      after RFA. The imaging consisted of (11)C-5-HTP-PET, CEUS and CECT on all three
      occasions. RESULTS: Thirty RFA areas were evaluated, and residual tumors (RTs)
      were depicted in eight areas (22%). (11)C-5-HTP-PET depicted RTs after RFA with
      maximum sensitivity (100%) and specificity (100%), using radiological follow-up
      as the gold standard. (11)C-5-HTP-PET detected five out of eight RTs earlier than
      CECT or CEUS. In general, the sensitivity of (11)C-5-HTP-PET exceeded that of
      CECT and CEUS for early visualization of NET liver metastases. CONCLUSION: (11)C
      5-HTP-PET can be used in the follow-up after RFA for the purpose of detecting RT,
      and it provides additional information to CEUS and CECT by detecting new lesions.

PMID- 22381781
TI  - High molecular mass radioimmunoconjugates are promising for intraperitoneal alpha
      emitter immunotherapy due to prolonged retention in the peritoneum.
AB  - INTRODUCTION: Therapeutic efficacy of intraperitoneal radioimmunotherapy is
      dependent on the time of retention of the radioimmunoconjugates within the
      peritoneal cavity. Therefore, the aim of this study was to investigate
      intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. METHODS:
      Female Balb/c mice were injected with 213Bi- or 111In-labeled IgM, IgG and
      recombinant Fab conjugates intraperitoneally or intravenously. At different time
      points after injection, whole body distribution of radionuclides was imaged using
      a gamma camera. Distribution of radionuclides in selected organs was determined
      via gamma-counting after sacrifice. Biological half-lives of the conjugates were
      calculated from whole body activities. RESULTS: After i.p. injection 213Bi-Fab
      rapidly accumulated in the kidneys indicative of glomerular filtration and
      reabsorption. Accumulation of 213Bi-IgG in the kidneys was significantly lower.
      213Bi-IgM showed a striking accumulation in the liver 180 min after i.p.
      injection. 111In-IgG persisted in the circulation up to 72 h both after i.p. and
      i.v. injection. 111In-IgM showed a continuous accumulation in the liver.
      Moreover, 111In-IgM was significantly higher 24 h after i.v. injection than i.p.
      injection both in liver and spleen. These differences could be confirmed via
      scintigraphy. After injection of 111In-IgG differences in scintigraphic images
      between i.v. and i.p. were clearly visible only at 3 h. Biological half lives
      were 24 h, 45 h and 165 h for 111In-IgM, 111In-Fab and 111In-IgG, respectively.
      CONCLUSIONS: Retention of radioimmunoconjugates in the peritoneal cavity
      positively correlates with the molecular mass of the antibody. Therefore, IgM
      radioimmunoconjugates should be preferably used in radioimmunotherapy of free
      floating tumor cells and small tumor cell clusters in the ascites of the
      peritoneal cavity.

PMID- 22381782
TI  - Preparation and evaluation of bombesin peptide derivatives as potential tumor
      imaging agents: effects of structure and composition of amino acid sequence on in
      vitro and in vivo characteristics.
AB  - OBJECTIVES: Among the many clinically relevant peptide receptor systems, bombesin
      (BN) receptors have attracted enormous attraction due to their overexpression in
      various frequently occurring human tumors including breast and prostate, thus
      making such receptors promising targets with radiolabeled BN analogs. The present
      study describes the preparation and evaluation of a series of new BN derivatives
      as potential tumor imaging agents. METHODS: Several new BN derivatives with the
      common structure MAG(3)-X-BN(1-14 or 6-14), where X=Asp or Asp-Asp, were
      synthesized by solid-phase peptide synthesis. S-benzoylmercaptoacetic acid was
      incorporated at the end of synthesis via manual conjugation to yield MAG(3)-BN
      conjugates. Radiolabeling with (99m)Tc was accomplished by ligand exchange
      method. The receptor-binding affinity assays were performed in MDA-MB-231, MCF-7,
      T47-D and PC-3 cancer cell lines. In vivo biodistribution and clearance kinetics
      were assessed in Balb/c mice, and tumor targeting efficacy was determined in nude
      mice bearing breast tumor xenografts. RESULTS: The peptides were prepared
      conveniently and radiolabeled efficiently with (99m)Tc (up to 95% labeling
      efficiency). In vitro cell binding assays demonstrated high affinity (values in
      the nanomolar range) of (99m)Tc peptides towards breast and prostate cancer cell
      lines. In addition, the radioconjugates displayed significant internalization
      (values ranged between 19% and 35%) in tumor cells. In vivo biodistribution and
      biokinetics are characterized by efficient clearance from the blood and variable
      degrees of excretion through the renal pathway. In vivo tumor targeting studies
      displayed variable uptake capacity of different BN derivatives, underlining the
      influence of specific amino acid sequence on tumor targeting profiles. Tumor
      uptake was always higher than the radioactivity in the blood and muscle, with
      good tumor retention and good tumor-to-blood and tumor-to-muscle ratios,
      indicating the potential of these agents for targeting tumors in vivo.
      CONCLUSIONS: The combination of favorable in vitro and in vivo properties may
      render these BN peptides as potential candidates for targeting BN/GRP receptor
      positive tumors. They deserve further evaluation to determine their real
      strength. The present data indeed provide useful information regarding peptide
      structure-pharmacologic activity relationship, which might be useful in designing
      and developing new BN-like peptides for efficient targeting of tumors in vivo.

PMID- 22381783
TI  - Repeatability of FDG quantification in tumor imaging: averaged SUVs are superior
      to SUVmax.
AB  - PURPOSE: Reliable 18F-fluorodeoxyglucose (FDG) uptake quantification is crucial
      for cancer treatment monitoring. While interobserver variability has been found
      to be lower for a maximum standard uptake value (SUV)max than for an averaged SUV
      (SUVmean), the repeatability has not been investigated yet. In this study, we
      determined the repeatability of SUV values in two sequential measurements 5 min
      apart. METHODS: Positron emission tomography data of malignant chest tumors were
      acquired dynamically during 45 min in 20 patients. SUV values were derived from
      the hottest (SUVmax), the mean of the 5 (SUV5) and 10 (SUV10) hottest voxels and
      the mean of a volume of interest (SUVmean). The repeatability of the SUV
      measurements was determined as the standard deviation of the difference between
      the values at 40 and 45 min and represented as Bland-Altman graphs. RESULTS: The
      standard deviation of the difference between the two sequential scans for SUVmax,
      SUV5, SUV10 and SUVmean was 1.01, 0.53, 0.37 and 0.28. CONCLUSION: The
      repeatability of SUV is markedly increased by deriving the value from multiple
      voxels. Compared to SUVmax, the variability in SUV measurements is reduced by a
      factor of 2.7 (2.7=1.01/0.37) if 10 voxels are pooled.

PMID- 22381785
TI  - Density functional theory, comparative vibrational spectroscopic studies, NBO,
      HOMO-LUMO analyses and thermodynamic functions of N-(bromomethyl)phthalimide and
      N-(chloromethyl)phthalimide.
AB  - Quantum mechanical calculations of energies, geometries, and vibrational
      wavenumbers of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide are
      carried out using density functional theory (DFT/B3LYP) method with 6-31G and 6
      311G(d,p) basis sets. The optimized geometrical parameters obtained by B3LYP
      method show good agreement with experimental data. The difference between the
      observed and scaled wavenumber values of most of the fundamentals is very small.
      A detailed interpretation of the infrared and Raman spectra of N
      (bromomethyl)phthalimide and N-(chloromethyl)phthalimide was also reported. The
      calculated HOMO and LUMO energies show that charge transfer occurs in the
      molecules. The thermodynamic functions of N-(bromomethyl)phthalimide and N
      (chloromethyl)phthalimide have been performed at B3LYP/6-31G and B3LYP/6
      311G(d,p) basis sets. The theoretical spectrograms for FT-IR and FT-Raman spectra
      of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide have also been
      constructed.

PMID- 22381786
TI  - New iridium complexes with cyclometalated 2-arylimidazole ligands as highly
      efficient saturated green emitters.
AB  - Phosphorescence studies of a series of heteroleptic cyclometalated iridium(III)
      complexes have been carried out. From the photoluminescent properties, it was
      found that these complexes possess dominantly (3)MLCT and (3)pi-pi* excited
      states. The solvent shifts are interpreted in terms of Reichardt-Dimroth solvent
      E(T) parameters and Marcus theory. The results are consistent with prior
      assignments on the absorption band to a metal-to-ligand charge transfer excited
      state associated with chelating ligand. Emission kinetic studies reveal that k(r)
      increases with increasing lambda(em) and linear correlation between ln(k(nr)) and
      energy gap. The effect of E(g) and DeltaQ(e) on k(nr) is discussed in detail.

PMID- 22381787
TI  - Vibrational, conformational and electronic structure investigations of
      alpha,alpha'-dibromo-o-xylene, alpha,alpha'-dibromo-m-xylene and alpha,alpha'
      dibromo-p-xylene.
AB  - The Fourier transform infrared (FTIR) and FT-Raman spectra of alpha,alpha'
      dibromo-o-xylene (DBOX), alpha,alpha'-dibromo-m-xylene (DBMX) and alpha,alpha'
      dibromo-p-xylene (DBPX) of the configuration BrCH(2)C(6)H(4)CH(2)Br have been
      recorded in the range 4000-400 and 4000-100 cm(-1), respectively. The
      conformational analysis of these compounds was performed. The complete
      vibrational assignment and analysis of the fundamental modes of the most stable
      conformer of the compounds were carried out using the experimental FTIR and FT
      Raman data, and quantum mechanical studies. The observed vibrational frequencies
      were compared with the wavenumbers derived theoretically for the optimized
      geometry of the compounds from the DFT-B3LYP gradient calculations employing the
      standard 6-31G**, high level 6-311++G** and cc-pVTZ basis sets. The structural
      parameters and vibrational wavenumbers obtained from the DFT method are in good
      agreement with the experimental data. The potential energy distributions of the
      fundamental modes were also calculated with DFT force fields utilizing Wilson's
      FG matrix method. The effect of -CH(2)Br group on the skeletal vibrations has
      been discussed.

PMID- 22381788
TI  - Highly selective ensembles for D-fructose based on fluorescent method in aqueous
      solution.
AB  - Three highly sensitive and selective switches for monosaccharides were composed
      by anionic polyelectrolyte PPPSO(3)Na and cationic viologen quencheres BBVs. The
      sensing processes of three ensembles (PPPSO(3)Na/o-BBV, PPPSO(3)Na/m-BBV and
      PPPSO(3)Na/p-BBV) to common seven monosaccharides have been determined by
      fluorescence spectra at pH 7.4 buffer solution. The results show that the three
      sensing ensembles all embody higher selectivity and sensitivity for d-fructose
      with reversible "on-off-on" fluorescence response. The research results can
      provide a new mode for developing highly selective probes.

PMID- 22381789
TI  - Conformational mobility of small molecules in glass-forming solutions studied by
      FTIR spectroscopy.
AB  - Small molecules with two or more stable conformations when embedded in a glass
      forming liquid (matrix) serve the role of "conformational probes", i.e., their
      conformational transitions are used to follow local mobility in the matrix. In
      the present study, conformational probes were embedded in low-molecular-weight
      glass-forming liquids, and the molecular mobility was studied in a broad
      temperature range including the glass transition temperature (T(g)). Paraffin
      oil, dibutylphthalate, bis(2-ethylhexyl)phthalate and isopropylbenzene were used
      as glass-forming liquids while 1,2-dichloroethane, 1,2-diphenylethane,
      chlorocyclohexane and bromocyclohexane were used as conformational probes. For
      some of the matrix/probe systems, the conformational mobility was found to freeze
      in at T(g), while for the others it froze-in at certain temperatures T(f)<T(g).
      In the latter case, it was possible to evaluate the activation energies related
      to mobility of free volume entities in the glassy matrices. In addition, it was
      possible to estimate the volumes of sub-molecular groups of the matrix that
      freeze-in at T(f).

PMID- 22381790
TI  - Nanofibers doped with a novel red-emitting Europium complex: synthesis,
      characterization, photophysical property and sensing activity toward molecular
      oxygen.
AB  - In this paper, we synthesize a novel diamine ligand of DIQ-Et and its
      corresponding Eu(III) complex of Eu(TTA)(3)DIQ-Et, where DIQ-Et=N-ethyl-10H
      dipyrido-[f,h]-indolo-[3,2-b]-quinoxaline, and TTA=2-thenoyltrifluoroacetonate.
      The UV-vis absorption, photoluminescence, low temperature phosphorescence, energy
      transfer mechanism, and excited state lifetime of Eu(TTA)(3)DIQ-Et are
      investigated in detail. Data suggest that the emission of Eu(TTA)(3)DIQ-Et is
      quenchable by molecular oxygen due to the back-energy transfer process. By doping
      Eu(TTA)(3)DIQ-Et into a polymer matrix of poly(vinylpyrrolidone) (PVP), oxygen
      sensing performance of the resulted nanofibers is investigated. Finally, the 0.7
      wt% doped sample exhibits a linear response toward molecular oxygen, with a
      sensitivity of 2.4 and response/recovery time of 12s/16s.

PMID- 22381791
TI  - Effects of solvent and substituent on the electronic absorption spectra of some
      substituted Schiff bases: a chemometrics study.
AB  - A series of Schiff bases were studied for their delicate changes in absorption
      electronic spectra by changing substituents and solvents. UV/vis absorbance
      spectra of Schiff base derivatives of different substituents ranging from
      electron withdrawing to electron donating (Br, CF(3), Cl, CN, CO(2)H, F, Me,
      NO(2), OH, OMe, H) were studied in different solvents (acetonitrile, chloroform,
      cyclohexane, dioxane, dimethylsulfoxide and methanol). Linear relationships were
      established to investigate the effect of solute structure and solvatochromic
      parameters of solvents on the absorbance spectra. Meaningful chemical factors and
      then regression models were provided utilizing factor analysis (FA) and multiple
      linear regression (MLR). It was found that the frequency of maximum absorbance
      was mainly controlled by the solvent's dipolarity/polarizability. The lambda(max)
      of the ortho-nitro derivative represented the largest dependency on solvents'
      polarity/polarizability so that it can be used as a solvatochromic probe.

PMID- 22381792
TI  - Molecular structure and vibrational spectra of 3-and 4-amino-2-bromopyridine by
      density functional methods.
AB  - In this work, experimental and theoretical study on the molecular structure and
      the vibrational spectra of 3-amino-2-bromopyridine (Compound I) and 4-amino-2
      bromopyridine (Compound II) are presented. The vibrational frequencies of these
      compounds were obtained theoretically by DFT/B3LYP employing the 6-311G(2df,2p)
      basis set for optimized geometries and were compared with Fourier Transform
      Infrared solid phase spectra (FTIR) in the region of 400-4000 cm(-1), FT-Raman
      spectra in the region of 100-4000 cm(-1) and with solution phase spectra in the
      region of 400-4000 cm(-1). Complete vibrational assignment, analysis and
      correlation of the fundamental modes for these compounds have been carried based
      on the potential energy distribution (PED). The vibrational harmonic frequencies
      were scaled using scale factors, yielding a good agreement between the
      experimentally recorded and the theoretically calculated values. Finally the
      calculated HOMO and LUMO energies are localized on the entire ring and
      substituents.

PMID- 22381793
TI  - Structural and spectroscopic diagnosis of Eu:ZnO and Eu:Yb:ZnO glass and
      ceramics.
AB  - Eu and Eu:Yb codoped ZnO nanocrystals embedded in B(2)O(3) glass matrix were
      synthesized and their structural, optical properties were discussed. On
      excitation with 532 nm laser radiation intense orange/red emissions from Eu(3+)
      ions were observed. The fluorescence intensity was found to enhance on annealing.
      Frequency upconversion emissions from Eu(3+) ions were observed in presence of
      Yb(3+) ions on excitation with NIR (976 nm) laser. The enhancement in emission
      intensity was explained and the photo-physics involved is linked with the unique
      structural properties of the crystallites formed. Ion interactions and the
      different energy transfer parameters were also calculated.

PMID- 22381794
TI  - Development of an extractive spectrophotometric method for estimation of uranium
      in ore leach solutions using 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester
      (PC88A) and tri-n-octyl phosphine oxide (TOPO) mixture as extractant and 2-(5
      bromo-2-pyridylozo)-5-diethyl aminophenol (Br-PADAP) as chromophore.
AB  - An extractive spectrophotometric analytical method has been developed for the
      determination of uranium in ore leach solution. This technique is based on the
      selective extraction of uranium from multielement system using a synergistic
      mixture of 2-ethylhexyl phosphonic acid-mono-2-ethylhexyl ester (PC88A) and tri-n
      octyl phosphine oxide (TOPO) in cyclohexane and color development from the
      organic phase aliquot using 2-(5-Bromo-2-pyridylazo)-5-diethyl aminophenol (Br
      PADAP) as chromogenic reagent. The absorption maximum (lambda(max)) for UO(2)(2+)
      Br-PADAP complex in organic phase samples, in 64% (v/v) ethanol containing buffer
      solution (pH 7.8) and 1,2-cyclohexylenedinitrilotetraacetic acid (CyDTA)
      complexing agent, has been found to be at 576 nm (molar extinction coefficient,
      E: 36,750 +/- 240 L mol(-1)cm(-1)). Effects of various parameters like stability
      of complex, ethanol volume, ore matrix, interfering ions etc. on the
      determination of uranium have also been evaluated. Absorbance measurements as a
      function of time showed that colored complex is stable up to > 24h. Presence of
      increased amount of ethanol in colored solution suppresses the absorption of a
      standard UO(2)(2+)-Br-PADAP solution. Analyses of synthetic standard as well as
      ore leach a solution show that for 10 determination relative standard deviation
      (RSD) is < 2%. The accuracy of the developed method has been checked by
      determining uranium using standard addition method and was found to be accurate
      with a 98-105% recovery rate. The developed method has been applied for the
      analysis of a number of uranium samples generated from uranium ore leach
      solutions and results were compared with standard methods like inductively
      coupled plasma emission spectrometry (ICPAES). The determined values of uranium
      concentrations by these methods are within +/- 2%. This method can be used to
      determine 2.5-250 MUg mL(-1) uranium in ore leach solutions with high accuracy
      and precision.

PMID- 22381795
TI  - Green synthesis of silver nanoparticles using Terminalia chebula extract at room
      temperature and their antimicrobial studies.
AB  - A green rapid biogenic synthesis of silver nanoparticles (Ag NPs) using
      Terminalia chebula (T. chebula) aqueous extract was demonstrated in this present
      study. The formation of silver nanoparticles was confirmed by Surface Plasmon
      Resonance (SPR) at 452 nm using UV-visible spectrophotometer. The reduction of
      silver ions to silver nanoparticles by T. chebula extract was completed within 20
      min which was evidenced potentiometrically. Synthesised nanoparticles were
      characterised using UV-vis spectroscopy, Fourier transformed infrared
      spectroscopy (FT-IR), powder X-ray diffraction (XRD), transmission electron
      microscopy (TEM) and atomic force microscopy (AFM). The hydrolysable tannins such
      as di/tri-galloyl-glucose present in the extract were hydrolyzed to gallic acid
      and glucose that served as reductant while oxidised polyphenols acted as
      stabilizers. In addition, it showed good antimicrobial activity towards both Gram
      positive bacteria (S. aureus ATCC 25923) and Gram-negative bacteria (E. coli ATCC
      25922). Industrially it may be a smart option for the preparation of silver
      nanoparticles.

PMID- 22381796
TI  - Bioinspired synthesis of highly stabilized silver nanoparticles using Ocimum
      tenuiflorum leaf extract and their antibacterial activity.
AB  - Biosynthesis of nanoparticles is under exploration due to wide biomedical
      applications and research interest in nanotechnology. We herein reports
      bioinspired synthesis of silver nanoparticles with the aid of novel, non toxic
      ecofriendly biological material namely Ocimum tenuiflorum leaf extract. It acts
      as reducing as well as stabilizing agent. An intense surface plasmon resonance
      band at ~450 nm in the UV-visible spectrum clearly reveals the formation of
      silver nanoparticles. The photoluminescence spectrum was recorded to study
      excitation and emission. TEM and PSD by dynamic light scattering studies showed
      that size of silver nanoparticles to be in range 25-40 nm. Face centered cubic
      structure of silver nanoparticles are confirmed by SAED pattern. The charge on
      synthesized silver nanoparticles was determined by zeta potential. The colloidal
      solution of silver nanoparticles were found to exhibit high antibacterial
      activity against three different strains of bacteria Escherichia coli (Gram
      negative), Corney bacterium (gram positive), Bacillus substilus (spore forming).

PMID- 22381797
TI  - Synthesis, characterization and DFT study of methoxybenzylidene containing
      chromophores for DSSC materials.
AB  - Novel tricyanovinyl derived from hydrazones have been prepared by the reaction of
      tetracyanoethylene and phenylethylidene hydrazone, and these dyes showed
      absorption in the region of 539-650 nm. The dyes showed pronounced solvatochromic
      effects as the polarity of the solvents changed. The torsion in E isomer is
      smaller than Z and azo isomers of MBD1 and MBD2. The HOMOs are delocalized on
      whole of the molecule while LUMOs are distributed on the tricarbonitrile. The
      LUMO energies are above the conduction band of TiO(2) and HOMOs of the dyes are
      below the redox couple of MBD1 and MBD2. The HOMO energies, LUMO energies and
      HOMO-LUMO energy gap of MBD1 and MBD2 are almost same. The absorption spectra of
      both the dyes in different solvents are approximately same except in cyclohexane.

PMID- 22381798
TI  - Studies on the Q-branch spectral lines of high-lying rovibrational transitions of
      diatomic system.
AB  - An analytical formula is suggested to predict the accurate Q-branch spectral
      lines of rovibrational transitions for diatomic systems by taking multiple
      spectral differences, and is applied to study the high-lying Q-branch emission
      spectra of the (0, 0) band of the 4Gamma5/2-4Phi3/2 and 4Gamma7/2 -4Phi5/2
      systems of TiF molecule using fifteen known accurate experimental transition
      data. The results show that not only the known experimental transition lines are
      accurately reproduced, but also the correct values of the unknown spectral lines
      are predicted.

PMID- 22381799
TI  - Density functional theory study on characterization of 3-chloro-1,2
      benzisothiazole.
AB  - The FT-IR and FT-Raman spectra of 3-chloro-1,2-benzisothiazole (CBT) have been
      recorded and analyzed. Theoretical information on the optimized geometry,
      harmonic vibrational frequencies, infrared and Raman intensities were obtained by
      means of density functional theory (DFT) gradient calculations, using 6
      311++G(d,p) basis set. Mulliken population analysis shows charge distribution on
      the molecule. Thermodynamic properties like entropy, heat capacity, zero point
      energy have been calculated for the molecule. The calculated HOMO and LUMO
      energies show the charge transfer occurs within the molecule. Stability of the
      molecule has been analyzed using Natural Bond Orbital (NBO) and Natural Localized
      Molecular Orbital (NLMO) analysis. The results of the calculations were applied
      to simulated spectra of the title compound, which show the excellent agreement
      with the observed spectra.

PMID- 22381800
TI  - Calculated infrared spectra of nerve agents and simulants.
AB  - Since organophosphorus nerve agents are among the most toxic known chemical
      warfare agents, it is desirable to have a way to distinguish between one and
      another. Infrared spectroscopy is a common tool for identifying molecules. Given
      the difficulty in handling these chemicals, calculated IR spectra can be useful.
      Calculated IR spectra are presented for G agents, V agents, and simulants.
      Quantum chemistry calculations were performed using the Gaussian 03 package at
      the B3LYP/6-31+G(d,p) level of theory. The most prominent IR lines are due to
      vibrations of P-O-C and P=O groups within the molecules. It should be possible to
      distinguish between the G-series and V-series agents using IR spectroscopy, but
      unique identification of individual chemical agents is unlikely.

PMID- 22381801
TI  - 2-Methoxyphenyl isocyanate and 2-Methoxyphenyl isothiocyanate: conformers,
      vibration structure and multiplet Fermi resonance.
AB  - IR and Raman spectral measurements in the region 3500-400/50 cm(-1) have been
      made for the liquid samples of 2-Methoxyphenyl isocyanate and 2-Methoxyphenyl
      isothiocyanate. A complete assignment of the measured bands has been proposed as
      aided by conformational and vibration analyses at B3LYP/6-311++G** level of
      calculations. Three conformers for 2-Methoxyphenyl isocyanate and two for 2
      Methoxyphenyl isothiocyanate have been determined. The tilt of the isocyanate
      (NCO) and isothiocyanate (NCS) moieties with respect to phenyl ring are in broad
      agreement with their parents. Stretching mode frequencies of methyl group (
      OCH(3)) in 2-Methoxyphenyl isocyanate have been lowered in the 2900-2800 cm(-1);
      deformation asymmetric modes are IR strong and symmetric one Raman strong. In 2
      Methoxyphenyl isothiocyanate, a similar pattern is true for stretching modes but
      deformation asymmetric modes are IR strong and symmetric mode has not been
      observed. Multiplet absorption band system near 2200 cm(-1) in 2-Methoxyphenyl
      isocyanate has been interpreted to be caused by Fermi resonance. A similar
      pattern in absorption near 2100 cm(-1) in 2-Methoxyphenyl isothiocyanate but more
      complex Raman band pattern has also been explained through Fermi resonance from
      heuristic stand-point. Many Raman modes in 1300-1100 cm(-1) are intensified
      apparently owing to isothiocyanate than isocyanate moiety. Phenyl ring breathing
      mode is shifted to 1040 cm(-1) as strong Raman; the symmetric stretching mode of
      O-CH(3) near 1023 cm(-1) as strong absorption.

PMID- 22381802
TI  - Low-temperature electrolytic coloration and spectral properties of sucrose
      crystals.
AB  - Sucrose crystals are colored electrolytically at low temperatures and various
      voltages by using a pointed cathode and a flat anode. Caramels, carbonyl
      compounds, glycosylamines and free radicals are produced in colored sucrose
      crystals. No obvious characteristic absorption band in UV and visible wavelength
      regions is observed in absorption spectrum of uncolored sucrose crystal. Intense
      characteristic absorption bands of glycosylamines, carbonyl compounds and
      caramels are observed in absorption spectra of colored sucrose crystals.
      Production of caramels, carbonyl compounds, glycosylamines and free radicals are
      explained. Current-time curve for electrolytic coloration of sucrose crystal and
      its relationship with electrolytic coloration process are given.

PMID- 22381803
TI  - Molecular structures of 2-arylaminomethyl-1H-benzimidazole: spectral,
      electrochemical, DFT and biological studies.
AB  - In the present work, structural studies on (1H-benzimidazol-2-ylmethyl)-N-(4
      chloro-phenyl)-amine (L(1)) and (1H-benzimidazol-2-ylmethyl)-N-(4-iodo-phenyl)
      amine (L(2)) have been done extensively by a variety of physico-chemical
      techniques. Optimized geometrical structures, harmonic vibrational frequencies,
      natural bonding orbital (NBO) analysis, and Frontier molecular orbitals (FMO)
      were obtained by DFT/B3LYP method. TD-DFT calculations help to assign the
      electronic transitions. The polarizable continuum model (PCM) fails to describe
      the experimental chemical shift associated with the NH protons as calculated by
      applying Gauge-invariant atomic orbital (GIAO) method, but a very good
      correlation between the theoretical and experimental values was achieved by
      taking into account the specific solute-solvent interactions. DFT calculations
      showed a good agreement between the theoretical and observed results. These
      compounds exhibited a high biological activity through the inhibition of the
      metabolic growth of the investigated bacteria.

PMID- 22381804
TI  - A study of Ganoderma lucidum spores by FTIR microspectroscopy.
AB  - In order to obtain unique information of Ganoderma lucidum spores, FTIR
      microspectroscopy was used to study G. lucidum spores from Anhui Province (A),
      Liaoning Province (B) and Shangdong Province (C) of China. IR micro-spectra were
      acquired with high-resolution and well-reproducibility. The IR spectra of G.
      lucidum spores from different areas were similar and mainly made up of the
      absorption bands of polysaccharide, sterols, proteins, fatty acids, etc. The
      results of curve fitting indicated the protein secondary structures were
      dissimilar among the above G. lucidum spores. To identify G. lucidum spores from
      different areas, the H1078/H1640 value might be a potentially useful factor,
      furthermore FTIR microspectroscopy could realize this identification efficiently
      with the help of hierarchical cluster analysis. The result indicates FTIR
      microspectroscopy is an efficient tool for identification of G. lucidum spores
      from different areas. The result also suggests FTIR microspectroscopy is a
      potentially useful tool for the study of TCM.

PMID- 22381805
TI  - Use of web-based patient education sessions on psychiatric wards.
AB  - OBJECTIVE: To evaluate the use of web-based patient education sessions in the
      psychiatric inpatient care. METHODS: The qualitative and quantitative data was
      collected from 93 patients' evaluation reports in two psychiatric hospitals in
      Finland completed by 83 nurses. RESULTS: The web-education included six patient
      education sessions which were used over a period lasting between 1 and 70 days
      and took 10-360 min per patient. Out of 508 sessions, 464 had no interruptions or
      disturbances, 37 sessions had disturbances and seven sessions were interrupted.
      Three fourths of the sessions were used successfully. Factors associated with use
      were patients' vocational education level, mental status, diagnoses, number of
      nurses involved and hospital. CONCLUSION: It is important to invest effort in web
      based patient education during patients' hospitalization and to use it even with
      patients suffering from serious mental health disorders. This is meant to provide
      more alternatives in nursing.

PMID- 22381806
TI  - Pathologist's puzzle: Membranoproliferative glomerulonephritis-like features in
      cryoglobulinemic glomerulonephritis.
AB  - Mixed cryoglobulinemia is commonly related to chronic HCV infection, and renal
      complications occur frequently. Typical renal involvement presents with diffuse
      proliferative glomerular pathology, similar to membranoproliferative
      glomerulonephritis, with necrotizing arteritis of medium-sized vessels, referred
      to as cryoglobulinemic glomerulonephritis. However, the histological appearance
      may vary according to the clinical presentation and treatment applied. Not only
      membranoproliferative glomerulonephritis but also certain types of systemic
      vasculitis (Systemic Lupus Erythematosus, Polyarteritis Nodosa), thrombotic
      microangiopathy, and Waldenstrom's Macroglobulinemia may exhibit similar
      histopathological findings in the biopsy with cryoglobulinemic
      glomerulonephritis. For an optimal differential diagnosis, clinicopathological
      correlation and serological findings should accompany the pathological findings.
      We present a case of cryoglobulinemic glomerulonephritis, and discuss the
      differential diagnosis in detail.

PMID- 22381807
TI  - Lifetime leisure-time physical activity and the risk of depressive symptoms at
      the ages of 65-74 years: the FIN-D2D survey.
AB  - OBJECTIVES: To investigate the association between lifetime leisure-time physical
      activity (LTPA) and depressive symptoms (DS) based on the population-based FIN
      D2D cross-sectional survey conducted in 2007. METHODS: Nine hundred twenty seven
      randomly selected Finnish men and women aged 65-74 years were included in this
      study. DS were determined with the Beck Depression Inventory (>=10 points), and
      lifetime historical LTPA frequency from age 15 years onwards was recalled
      retrospectively. RESULTS: The frequency of LTPA was highest at the ages of 15-24
      years in both the DS present and not present groups (14.6 times per month). LTPA
      frequency was significantly lower among those with DS compared with those without
      DS at the age of 45-54 (10.0 vs. 11.3, p=0.041), 55-64 (9.6 vs. 12.6, p<0.001),
      and 65-74 (8.6 vs. 11.9, p<0.001). Also the prevalence of somatic diseases was
      higher for those with DS compared with participants without DS. CONCLUSIONS: This
      study reveals lifetime LTPA variation and its potential consequences. The
      relationship found between reduced lifetime LTPA and the occurrence of DS suggest
      that promoting LTPA throughout one's lifetime would be beneficial in terms of DS
      and somatic diseases in older age.

PMID- 22381808
TI  - Current role of cryotherapy in retinopathy of prematurity: a report by the
      American Academy of Ophthalmology.
AB  - OBJECTIVE: To evaluate the role of cryotherapy in the current treatment of
      retinopathy of prematurity (ROP). METHODS: Literature searches of PubMed and the
      Cochrane Library were conducted on December 2, 2009, for articles published after
      1984. The searches included all languages and retrieved 187 relevant citations.
      Thirteen articles were deemed relevant to the assessment question and were rated
      according to the strength of evidence. Four articles reported results from 2
      large multicenter randomized clinical trials, and the remaining 9 articles
      reported results of 3 small randomized trials that directly compared cryotherapy
      and laser. RESULTS: Neither of the multicenter randomized clinical trials was a
      direct comparison of cryotherapy with laser. These studies were used to evaluate
      the comparative trials based on treatment criteria, study populations, and
      clinical results. Higher percentages of poor structural and functional outcomes
      generally were seen in eyes treated with cryotherapy compared with eyes
      undergoing laser treatment. Higher rates of systemic complications and myopia
      also were identified after treatment with cryotherapy. CONCLUSIONS: Despite a
      relative paucity of level I evidence directly comparing cryotherapy and laser
      treatment for threshold ROP, the literature suggests that neonatal facilities
      should gain access to laser technology and laser-trained ophthalmic staff to
      achieve better outcomes for treatment of the disease.

PMID- 22381809
TI  - A randomized trial of tacrolimus versus tacrolimus and prednisone for the
      maintenance of disease remission in noninfectious uveitis.
AB  - PURPOSE: To compare tacrolimus monotherapy with tacrolimus and prednisone therapy
      for the maintenance of disease remission in subjects with noninfectious posterior
      segment intraocular inflammation (PSII). DESIGN: Randomized, controlled, phase
      2b, open-label, dual-center noninferiority trial. PARTICIPANTS: Fifty-eight
      patients with sight-threatening PSII. METHODS: Patients requiring a second-line
      systemic immunosuppressive agent to control their PSII were treated with
      therapeutic doses of oral tacrolimus. Those subjects who subsequently were able
      to taper their prednisone dose to 10 mg daily without disease reactivation were
      assigned randomly either to stop prednisone or to continue 7.5 to 10 mg
      prednisone daily for 9 months. MAIN OUTCOME MEASURES: Change in logarithm of the
      minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient
      withdrawal resulting from treatment inefficacy or intolerance. RESULTS: Thirty
      five patients successfully tapered their prednisone to 10 mg daily. Of these, 16
      were allocated randomly to receive tacrolimus monotherapy and 19 to continue
      taking prednisone and tacrolimus dual therapy. The difference in the mean change
      in VA for monotherapy compared with the dual therapy group was less than 1 logMAR
      letter (logMAR, -0.008; 95% confidence interval, -0.108 to 0.092; P = 0.870). The
      proportion of patients who tolerated treatment and maintained disease remission
      for 9 months after randomization also was similar in both groups (monotherapy,
      62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were
      the result of disease reactivation, whereas 50% of dual-therapy failures were the
      result of drug intolerance. CONCLUSIONS: This study provides preliminary evidence
      that corticosteroids can be withdrawn in tacrolimus-treated patients who are able
      to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual
      therapy in the prevention of disease reactivation was offset by its greater
      treatment intolerance. These findings support the further evaluation of
      corticosteroid-free treatment in future phase 3 trials (International Standard
      Randomised Controlled Trial Number Register identification, ISRCTN46576063).
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after
      the references.

PMID- 22381810
TI  - Assessment of real-time polymerase chain reaction detection of Acanthamoeba and
      prognosis determinants of Acanthamoeba keratitis.
AB  - OBJECTIVE: To evaluate the diagnostic value of real-time polymerase chain
      reaction (PCR) for detecting Acanthamoeba in eyes diagnosed with Acanthamoeba
      keratitis (AK) by conventional tests. In addition, to determine the preoperative
      prognosis-determining factors in eyes with AK. DESIGN: Retrospective, cross
      sectional study. PARTICIPANTS: A total of 104 eyes of 103 patients who were
      diagnosed with AK or with bacterial or bacteria-associated keratitis (BK) by
      conventional tests. METHODS: Twenty-nine eyes with AK and 75 eyes with BK were
      evaluated for Acanthamoeba and bacterial DNA by real-time PCR. The Acanthamoeba
      copy numbers, bacterial load, and clinical parameters in the patients with AK
      were assessed for those significantly associated with poor outcome, that is,
      final visual acuity of <20/50 or requiring keratoplasty, by logistic regression
      analysis. MAIN OUTCOME MEASURES: Acanthamoeba DNA copy number, bacterial DNA copy
      number, and odds ratio (OR) for poor prognosis. RESULTS: The detection of amoebic
      DNA was 50 times more sensitive by real-time PCR than by conventional cyst
      counting. The Acanthamoeba copy numbers at the first visit (mean: 4.7*10(5)+/
      3.2*10(5) copies) were significantly correlated with the AK stage, and both were
      significant risk factors for a poor outcome. The Acanthamoeba DNA copy numbers at
      the first visit and AK stage had a significantly high risk for poor outcome (OR
      of Acanthamoeba DNA copy per logarithm of copy numbers: 3.48, 95% confidence
      interval [CI], 1.04-111.63, P<0.05; OR of AK stage: 2.8 per stage increase, 95%
      CI, 1.07-7.30, P<0.05, after adjustment of age). In the AK cases with poor
      outcome, the amoebic DNA was not reduced by more than 90% after 1 month of
      treatment. The weak amoebic reduction was significantly associated with advanced
      AK stages or previous use of steroids. Bacterial 16S rDNA was detected in 53.6%
      of the eyes with AK, but it was not associated with any risk for refractoriness.
      CONCLUSIONS: Real-time PCR was effective in detecting and managing AK. The
      Acanthamoeba copy number and AK stage at the first visit were significantly
      associated with poor outcome. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 22381811
TI  - [Withdrawing and withholding treatments in acute severe stroke patients: clinical
      and ethical issues].
AB  - Stroke prognosis remains difficult to determine. It depends on stroke severity,
      patient's age and his rehabilitation ability. In essence, individual prediction
      is uncertain. Neurological severity is related to many factors such as low blood
      pressure or hyperthermia, which are important to consider before prognosticate.
      Do-not-resuscitate orders are given in up to 30% of acute stroke. More than 50%
      of them are given upon admission (in the first 24h of stroke). Withdrawing and
      withholding treatments are usually decided when neurological prognosis is
      supposed to be "catastrophic". Other factors, such as physician's disability
      representation or hospital use of aggressive procedures, certain daily routines
      or organizational constraints, are also probably implied. In France, end-of-life
      decisions are guided by the law: "loi relative aux droits des malades et a la fin
      de vie du 22 avril 2005". Palliative approach in severe stroke remains unknown
      and rarely developed, but is necessary to implement in such situations with high
      mortality rate. End-of-life decisions in severe stroke have several ethical
      issues such as the definition of what could be an "unacceptable" disability for
      the individual and/or the society.

PMID- 22381812
TI  - Predictors during childhood of future health-related quality of life in adults
      with Gilles de la Tourette syndrome.
AB  - BACKGROUND: Gilles de la Tourette syndrome (GTS) is a chronic neurodevelopmental
      disorder characterised by multiple motor and phonic tics and behavioural
      problems. Patients with GTS of all ages often report a poor health-related
      quality of life (HR-QOL). The diagnosis of GTS is usually established in
      childhood but little is known about factors that predict the long-term well-being
      of patients, especially in the presence of co-morbid behavioural problems. AIM:
      To investigate the childhood predictors of HR-QOL in a cohort of adult patients
      with GTS. METHODS: Forty-six patients with GTS aged 6-16 years underwent a
      baseline standardised clinical assessment of both tics and behavioural symptoms
      at a specialist GTS clinic. The same patients were re-assessed aged 16 years and
      above, with a mean follow-up period of 13 years (range 3-25 years), when they
      completed the Gilles de la Tourette Syndrome-Quality of Life Scale (GTS-QOL), a
      disease-specific measure of HR-QOL. RESULTS: Tic severity, premonitory urges and
      family history of GTS were identified as predictors during childhood of a poorer
      HR-QOL in adults with GTS by multiple linear regression analysis. Specifically,
      tic severity significantly predicted poor outcome across physical, psychological
      and cognitive domains of the GTS-QOL, reflecting widespread effects on HR-QOL.
      CONCLUSION: Young patients with severe tics associated with characteristic
      premonitory urges and a family history of tic disorders appear to be at higher
      risk for poorer HR-QOL as adults. Further prospective research into HR-QOL in GTS
      is required in order to inform long-term strategic resource allocation.

PMID- 22381813
TI  - Acoustic source localization in anisotropic plates.
AB  - The conventional triangulation technique cannot locate the acoustic source in an
      anisotropic plate because this technique requires the wave speed to be
      independent of the propagation direction which is not the case for an anisotropic
      plate. All methods proposed so far for source localization in anisotropic plates
      require either the knowledge of the direction dependent velocity profile or a
      dense array of sensors. In this paper for the first time a technique is proposed
      to locate the acoustic source in large anisotropic plates with the help of only
      six sensors without knowing the direction dependent velocity profile in the
      plate. Experimental results show that the proposed technique works for both
      isotropic and anisotropic structures. For isotropic plates the required number of
      sensors can be reduced from 6 to 4.

PMID- 22381814
TI  - Sigmoid sinus thrombosis as a sequela of head injury in children and its
      management.

PMID- 22381815
TI  - An ancient cause of muscle spasm... and an unhelpful magnetic resonance imaging
      scan.

PMID- 22381816
TI  - Indication for endoscopic third ventriculostomy.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) is increasingly prevalent
      among pediatric neurosurgeons as the initial treatment for hydrocephalus. The
      combination of ETV and choroid plexus cauterization (ETV/CPC) has improved the
      success rate among infants with hydrocephalus for whom ETV alone is much less
      successful. In parts of the developing world where there are economic and human
      resource constraints, this mode of treatment may be more appropriate than the
      routine use of shunts, which are prone to failures that require urgent surgical
      treatment. Here we review indications for the use of ETV or ETV/CPC as the
      primary treatment for hydrocephalus. CONCLUSION: Primary treatment of
      hydrocephalus by ETV can avoid shunt-dependence and its complications for many
      patients. Optimal results depend upon proper patient selection and the use of
      combined ETV/CPC when treating infants.

PMID- 22381817
TI  - Endoscopic management of complex hydrocephalus.
AB  - BACKGROUND: The management of complex hydrocephalus is challenging. There is no
      consensus of the best treatment for isolated fourth ventricles, arachnoid cysts,
      and multiloculated hydrocephalus, although the avoidance of multiple shunts is
      desirable. We reviewed our experience with the use of endoscopic techniques to
      simplify complex multicompartmental hydrocephalus to determine its efficacy and
      safety. METHODS: We performed a retrospective study of 114 consecutive adults and
      children undergoing endoscopic management of hydrocephalus by a single surgeon.
      The type of hydrocephalus and endoscopic procedure performed were recorded. The
      management algorithm for simplification of complex hydrocephalus is reviewed. All
      patients were followed up in the office or by telephone. RESULTS: A total of 143
      endoscopic procedures were performed on 114 patients with a mean age of 4.4 years
      (4 weeks to 32 years). The endoscopic procedures performed included cyst
      fenestration, septum pellucidotomy, endoscopic third ventriculostomy, aqueductal
      plasty with and without stent, and removal of cystercicotic cysts. Twenty-two
      (19.3%) patients had planned staged endoscopic procedures. Mean follow up was 65
      months (range 33-122 months). Eighty-two (72%) patients were reduced to 1 shunt,
      shunt independence was achieved in 32 (28%) patients, and only 8 (11%) patients
      required shunt revision in the follow-up period. CONCLUSIONS: Endoscopic
      simplification of complex hydrocephalus enables dependence on only a single shunt
      in the majority of patients, and a significant proportion achieve shunt
      independence. Endoscopic management should be considered before the placement of
      a second shunt, and some cases require staged endoscopic procedures to adequately
      communicate multicompartmental hydrocephalus.

PMID- 22381818
TI  - Complications of endoscopic third ventriculostomy.
AB  - BACKGROUND: The treatment of choice for several types of obstructive
      hydrocephalus is endoscopic third ventriculostomy (ETV). However, in certain
      cases ETV is not clearly superior to shunt placement, and a question of choice
      arises. Apart from the possibility of success in each case, knowledge of
      complication rates is of major importance as well. MATERIAL: Several series of
      ETVs have been published by various specialized centers. The reported overall
      complication rate is usually between 5% and 15%, and related permanent morbidity
      lower than 3%. The reported mortality of ETV is lower than 1%. RESULTS: The most
      frequent intraoperative complications of ETV are hemorrhage (the most severe
      being due to basilar rupture) and injury of neural structures. In the immediate
      postoperative period, hematomas, infections, and cerebrospinal fluid leaks may
      present. Morbidity can be neurological and/or hormonal. Systemic complications
      are related more to the patient's general status and less to the procedure
      itself. Late sudden deterioration, leading as a rule to a patient's death, has
      been reported. Its incidence is not exactly known, but probably is lower than
      0.1%. Nevertheless, the severity of this complication necessitates alertness and
      informing the patient. CONCLUSIONS: The complication rate of ETV is low, and
      rarely is a reason for choosing shunt placement instead. However, as a method it
      requires considerable experience, and several studies report a relation of
      experience not only with success rates but also with complication avoidance.

PMID- 22381819
TI  - Endoscopic aqueductoplasty and stenting.
AB  - OBJECTIVE: This paper discusses indications for and the technique of endoscopic
      aqueductoplasty with stenting. METHODS: We review and summarize the clinical
      experience with endoscopic aqueductoplasty gained over the last 15 years on
      pediatric and adult patients. RESULTS: Endoscopic aqueductoplasty with stenting
      presents a safe procedure. In well selected patients, it provides a long-term,
      stable clinical course. Aqueductoplasty alone has a high reclosure rate and
      should be avoided. CONCLUSIONS: Aqueductoplasty with stenting is the procedure of
      choice for the treatment of isolated fourth ventricle. Membranous and tumor
      related aqueductal stenosis should be treated by endoscopic third
      ventriculostomy.

PMID- 22381820
TI  - Neuroendoscopic management of middle fossa arachnoid cysts.
AB  - OBJECTIVE: The purpose of this study is to analyze symptomatic middle fossa
      arachnoid cysts and describe the advantages of the endoscopic technique to manage
      those cases that should be resolved surgically. METHODS: The physiopathology is
      described, and the clinical manifestations are analyzed. The diagnostic
      methodology and the surgical indications are presented. The endoscopic surgical
      technique is described thoroughly, and the advantages of the method are stated
      based on a series of 28 operated cases. The endoscope of choice has been a rigid
      endoscope with a 0 degrees  lens. RESULTS: All the cases in our series were
      solved by means of the endoscopic technique. One patient developed meningitis,
      recovering with antibiotic treatment, and 3 patients developed subdural hygromas:
      2 were treated by means of subdural-peritoneal shunting, and the remaining
      subdural hematoma required surgical drainage. All of the complications reported
      occurred in patients affected by cysts classified as Galassi type III. There was
      no mortality. CONCLUSIONS: The effectiveness of neuroendoscopic management of
      middle fossa arachnoid cysts has not yet been superseded by any other surgical
      treatment. It has been shown to be a simple, reliable, and fast procedure, with a
      low rate of complications and shorter hospital stay. In general, patients can
      resume their usual daily activities quite soon.

PMID- 22381821
TI  - Neuroendoscopic management of suprasellar arachnoid cysts.
AB  - BACKGROUND: The first case of an intracranial arachnoid cyst was described by
      Bright in 1831. In 1935, Barlow published the first case of a suprasellar
      arachnoid cyst. Fewer than 200 cases of suprasellar-prepontine arachnoid cysts
      have been reported in the literature as of January 2011. METHODS: Between 1994
      and 2010, the senior author operated on 34 cases of suprasellar-prepontine
      arachnoid cysts. Eighteen female and 16 male patients ranged in age from 6 days
      to 16 years (mean 5.2 years). Follow-up of the patients ranged from 1 year to 16
      years. RESULTS: Outcome may be evaluated according to radiological and clinical
      follow-up data. Postoperative radiological examinations must reveal: 1) the
      adequacy of fenestrations and flow through fenestration sites, 2) reduction of
      the cyst and ventricle size, and 3) reorientation of the chiasma and mammillary
      bodies to an acceptable anatomical position. In our series, no mortality
      occurred. Postoperative complication occurred in 3 cases. CONCLUSIONS:
      Suprasellar arachnoid cysts can be treated with favorable clinical and
      radiological results with endoscopic interventions when feasible. Results with
      ventriculocystocisternostomy are believed superior to those of
      ventriculocystostomy.

PMID- 22381822
TI  - Interhemispheric and quadrigeminal cysts.
AB  - BACKGROUND: Interhemispheric and quadrigeminal cysts are rare lesions, similar in
      their propensity to present in young babies and to be associated with other
      central nervous system malformations, such as corpus callosum agenesia,
      holoprosencephaly, encephalocele, and neuronal heterotopias. Recently endoscopy
      has become increasingly popular in the treatment of arachnoid cysts, but
      experience with cysts located in the interhemispheric fissure and in the
      quadrigeminal cistern is limited. METHODS: This study reviews the specific
      anatomy of interhemispheric and quadrigeminal cysts and their relationship with
      the ventricular system and subarachnoid cisterns to select the most appropriated
      treatment. It also reviews the literature on endoscopic treatment of
      interhemispheric and quadrigeminal cysts. RESULTS: Interhemispheric and
      quadrigeminal cysts are not homogeneous, they have different extensions toward
      surrounding regions. In most cases it is presented as an area of contiguity
      between the cyst and ventricular system and/or subarachnoid cisterns, making
      endoscopic treatment feasible. The success rate for endoscopic treatment is not
      different from that reported in large series of arachnoid cysts elsewhere.
      CONCLUSIONS: Endoscopic treatment should be considered the first-line option in
      the treatment of such lesions, even if some complications, such as subdural
      collections due to thinness of the cerebral mantle or subcutaneous CSF
      collections due to multifactorial associated hydrocephalus, must be expected.

PMID- 22381823
TI  - Magnetic resonance imaging of noncommunicating hydrocephalus.
AB  - INTRODUCTION: The purpose of this review is to describe the magnetic resonance
      imaging (MRI) findings in patients with noncommunicating hydrocephalus (NCH).
      METHODS: We describe the technical aspects of MR sequences that are of use for
      the imaging of cerebrospinal fluid (CSF). Both the diagnosis of NCH and the
      follow-up after endoscopic third ventriculostomy (ETV) are discussed through
      clinical cases. RESULTS: NCH is related to an obstacle hindering the CSF
      pathways. The combined use of anatomical and flow-sensitive MR sequences may help
      to characterize hydrocephalus. An imaging protocol is described at 1.5-T.
      CONCLUSIONS: The first step of the diagnostic work-up consists of the detection
      of an obstacle hindering CSF flow pathways using both constructive interference
      in steady state and flow-sensitive MR sequences. CSF volumetry and quantification
      of ventricular wall movement may also improve the diagnosis and follow-up of
      patients with NCH.

PMID- 22381824
TI  - Third ventriculostomy in normal pressure hydrocephalus.
AB  - Endoscopic third ventriculostomy (ETV) has become established as the treatment of
      choice in cases of uncomplicated occlusive hydrocephalus, but the clinical
      indications are continually being challenged. The role of ETV in so-called
      communicating hydrocephalus is often discussed within the context of the ongoing
      debate on cerebrospinal fluid flow pathways and the disruption caused by varying
      pathological entities. The increasing number of published reports outlining the
      efficacy of ETV in noncommunicating or obstructive hydrocephalus, with
      comparatively low complication rates, has led to attempts by some in the
      neurosurgical community to redefine its role in patients with communicating
      hydrocephalus and in particular normal pressure hydrocephalus. A randomized
      matched cohort with similar inclusion/exclusion criteria and objective and
      independent multidisciplinary assessments of preoperative assessment and
      postoperative outcome would be required to define the role of ETV in this group
      of patients.

PMID- 22381825
TI  - Endoscopic third ventriculostomy for idiopathic aqueductal stenosis.
AB  - BACKGROUND: Idiopathic aqueductal stenosis is a cause of noncommunicating
      hydrocephalus, which actual treatment with endoscopic third ventriculostomy (ETV)
      could assess without any interference with the etiology. The results of ETV in
      this indication therefore could be interpreted as the result of the surgical
      procedure alone, without any additional factors related to the etiology of the
      cerebrospinal fluid pathway obstruction, such as hemorrhage, infection, brain
      malformations, or brain tumors or cysts. METHODS: After a brief description of
      pathogenesis of hydrocephalus in aqueductal stenosis, the authors review the
      literature for studies on ETV, extrapolating patients with idiopathic aqueductal
      stenosis in infancy, childhood, and adulthood. Differences in outcome between
      patients treated with ETV and patients treated with ventriculoperitoneal shunt
      (VPS) are also reviewed. RESULTS: The overall success rates of ETV range between
      23% to 94%, with a mean of 68%; when only patients affected by obstructive
      triventricular hydrocephalus secondary to aqueductal stenosis are considered, the
      success rate is actually quite homogeneous and stable, being above 60% at any
      age, even if a trend in lower success rate in very young infants (younger than 6
      months of age) is noticeable. The few reports on intellectual outcome failed to
      demonstrate differences between ETV and VPS. CONCLUSIONS: Several issues, such as
      the cause of failures in well-selected patients, long-term outcome in infants
      treated with ETV, effects of persistent ventriculomegaly on neuropsychological
      developmental, remain unanswered. Larger and more detailed studies are needed.

PMID- 22381826
TI  - Redo third ventriculostomy.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) is the treatment of choice for
      obstructive hydrocephalus. In some cases a reclosure of the ventriculostoma
      occurs. This could be caused by different reasons, such as operative technique,
      size of the stoma, scarring, or a persisting Liliequist membrane. METHODS: The
      databases of the Neurosurgical Department of the Philipps University Marburg and
      the International Neuroscience Institute Hannover have been explored. The medical
      reports of patients who suffered from hydrocephalus and were treated with ETV
      between 1990 and 2010 were reviewed, with special consideration of a nonpatent
      ventriculostoma and a repeated ETV. RESULTS: Of 148 patients with ETV, we had 14
      patients in whom the stoma was not patent. In 8 of those, we performed a
      successful second ventriculostomy. Five patients were treated with application of
      a ventriculoperitoneal shunt. One patient died of an acute obstructive
      hydrocephalus due to the closure of the ventriculostoma. The success rate of
      repeat ETV has been 87.5%. CONCLUSIONS: In cases of secondary closure of the
      stoma after ETV, an endoscopic reventriculostomy is recommended using the same
      operative approach and should be taken into consideration before the application
      of a cerebrospinal fluid diversion system.

PMID- 22381827
TI  - The Neapolitan tradition of yacht clubs.

PMID- 22381828
TI  - Acute normovolemic hemodilution is safe in neurosurgery.
AB  - OBJECTIVE: To determine the safety of acute normovolemic hemodilution (ANH) for
      patients undergoing neurosurgical procedures. METHODS: A group of 100 patients
      undergoing neurosurgical procedures was assigned prospectively to receive ANH. A
      group of 47 patients who underwent craniotomy for aneurysm clipping and standard
      anesthetic management was used as a control. Procedures conducted under ANH were
      performed without significant variations in physiologic parameters. RESULTS:
      Compared with controls, intraoperative blood loss, operative time, incidence and
      grade of complications, and length of hospital stay were similar between the two
      groups. Although the ANH group showed a difference in prothrombin levels before
      and after hemodilution procedures, the levels were still considered within
      physiologic parameters. Platelet counts and partial thromboplastin time (PTT)
      levels indicated no significant variations in either group. During the ANH
      procedure, a considerable reduction of brain oxygen extraction was observed in
      individuals with worse preoperative neurologic status (P < 0.05), indicating
      potential benefit. Among patients with cerebral aneurysm, patients with good
      initial clinical grades had better clinical results as indicated by Glasgow
      Outcome Scale scores (P < 0.02). CONCLUSIONS: ANH is a safe procedure for
      patients undergoing neurosurgical procedures. Further studies are necessary to
      confirm the improvement in brain oxygen extraction and the clinical impact.
      Nonetheless, patients undergoing aneurysm clipping with good clinical grades seem
      to profit from ANH.

PMID- 22381829
TI  - A history of ventricular neuroendoscopy.
AB  - OBJECTIVE: To describe the history of neuroendoscopy through the history of the
      major neurosurgeons who worked and published in the field. METHODS: All relevant
      data described in publications before 1980 about the history of neuroendoscopy
      and found through OVID MEDLINE searches and related references are reported.
      RESULTS: Contributions of 14 neurosurgeons who were pioneers in neuroendoscopy
      are described in chronologic order: Lespinasse, Dandy, Payr, Mixter, Fay, Grant,
      Volkmann, Putnam, Dereymacker, Scarff, Feld, Guiot, Fukushima, and Griffith.
      CONCLUSIONS: An historical review of ventricular neuroendoscopy remains by
      essence incomplete. Medical technical progress proceeds by leaps and bounds,
      related to the ingenuity of surgeons able to understand rapidly the value of a
      technical change to improve their surgical procedure. The ability to remain
      attentive to patients and evolving pathologies as well as the evolution of modern
      technology is required to make further progress in neuroendoscopy.

PMID- 22381830
TI  - Neuroendoscopy: general aspects and principles.
AB  - When used in medicine, endoscopy describes a procedure used to see inside various
      parts of the body, such as the interior surfaces of an organ, by inserting a tube
      through a natural or created orifice. The instrument may have a rigid (borescope)
      or flexible (fiberscope) tube; it provides an image for visual inspection,
      photography and video-endoscopy and enables acquisition of biopsy specimens,
      removal of lesions, and retrieval of foreign objects. It is imperative that young
      neurosurgeons and residents become familiar and comfortable with endoscopic
      techniques, and it is hoped that they can contribute to the evolution and
      development of these surgical methods.

PMID- 22381831
TI  - Instrumentation: endoscopes and equipment.
AB  - OBJECTIVE: The technology and instrumentation for neuroendoscopy are described:
      endoscopes (principles, designs, applications), light sources, instruments,
      accessories, holders, and navigation. Procedures for cleaning, sterilizing, and
      storing are included. METHODS: The description is based on the author's own
      technical development and neuroendoscopic experience, published technology and
      devices, and publications on endoscopic surgery. RESULTS: The main work horses in
      neuroendoscopy are rigid glass rod endoscopes (Hopkins optics) due to the optical
      quality, which allows full high-definition video imaging, different angles of
      view, and autoclavability, which is especially important in neuroendoscopy due to
      the risk of Creutzfeldt-Jakob disease infection. Applications are endoscopy
      assistance to microsurgery, stand-alone endoscopy controlled approaches such as
      transnasal skull base, ventriculoscopy, and cystoscopy in the cranium. Rigid
      glass rod optics are also applicable in spinal endoscopy and peripheral nerve
      decompression using special tubes and cannulas. Rigid minifiberoptics with less
      resolution may be used in less complex procedures (ventriculoscopy, cystoscopy,
      endoscopy assistance with pen-designs) and have the advantages of smaller
      diameters and disposable designs. Flexible fiberoptics are usually used in
      combination with rigid scopes and can be steered, e.g. through the ventricles, in
      spinal procedures for indications including syringomyelia and multicystic
      hydrocephalus. Upcoming flexible chip endoscopes ("chip-in-the-tip") may replace
      flexible fiberoptics in the future, offering higher resolution and cold LED
      illumination, and may provide for stereoscopic neuroendoscopy. Various
      instruments (mechanical, coagulation, laser guides, ultrasonic aspirators) and
      holders are available. Certified methods for cleaning and sterilization, with
      special requirements in neuroapplications, are important. CONCLUSIONS:
      Neuroendoscopic instrumentation is now an established technique in neurosurgical
      practice and is experiencing rapid development (stereoscopy, integrated operating
      room).

PMID- 22381832
TI  - General principles and intraventricular neuroendoscopy: endoscopic techniques.
AB  - OBJECTIVE: To term and describe neuroendoscopic techniques. METHODS: A
      classification into three major groups of endoscopic techniques is presented.
      RESULTS: 1) Endoscopic neurosurgery ("channel" endoscopy) is mainly used in
      ventricular endoscopy. The surgical instruments are introduced via working
      channels that are located within the endoscope. 2) Endoscope-controlled
      microneurosurgery means that the endoscope is the only visualization tool and
      microsurgical instruments are used along the endoscope. Major applications are
      endonasal endoscopic skull base surgery, endoport surgery, and endoscopic
      transcranial surgery. 3) Endoscope-assisted microneurosurgery means that the
      microscope and the endoscope are used in the same surgery. The endoscopes are
      applied when hidden structures to be inspected are not visible in straight line
      with the microscope. CONCLUSIONS: Endoscopic techniques are a valuable addition
      to the neurosurgeon's armamentarium. Endoscopes are especially beneficial in deep
      and narrow surgical approaches and when "looking around a corner" is required.

PMID- 22381833
TI  - Intraventricular neuroendoscopy: complication avoidance and management.
AB  - In the modern era, neuroendoscopy has had an increasingly prominent role in
      neurosurgery. As attention has focused the development of minimally invasive
      surgical methods, neuroendoscopy has advanced both as an independent treatment
      modality for various neurologic disorders and as an adjunct to microneurosurgery.
      Neuroendoscopy is distinct from traditional surgery, and a thorough understanding
      of its unique attributes is required to attain maximal benefit. In addition to
      its advantages, neuroendoscopy is associated with unique obstacles that must be
      anticipated, appreciated, and accounted for to prevent complications. This
      article outlines techniques to reduce and manage complications during more common
      intraventricular neuroendoscopic procedures including endoscopic third
      ventriculostomy (ETV), colloid cyst resection, tumor biopsy and resection, and
      treatment of loculated hydrocephalus.

PMID- 22381834
TI  - The dedicated endoscopic operating room.
AB  - BACKGROUND: The establishment of neuroendoscopy has been one of the major
      achievements in neurosurgery in the last 2 decades. The use of the endoscope
      increases efficacy and safety in each procedure. METHODS: The integration of
      endoscopy with other operating techniques or imaging technologies enhances the
      safety and reliability of the technique. RESULTS: The efficacy of the procedures,
      patient safety, and extent of resection have been increased by the integration of
      endoscopy with all of these sophisticated operative tools and imaging sources.
      Endoscopy has led to shortening of operative time and of the duration of hospital
      stay. CONCLUSIONS: A dedicated endoscopic operating room should provide workflow
      optimization, ergonomic solutions, and highest safety standards for the patient.

PMID- 22381835
TI  - The incorporation of neuroendoscopy in neurosurgical training programs.
AB  - Previously considered the domain of the otolaryngologists, the endoscopy is now a
      common part of the armamentarium of a neurosurgeon. Neuroendoscopy or endoscope
      assisted microsurgery is now being used in almost all routine procedures
      performed in the neurosurgical operating room. Hands-on training has become
      essential to learn the basics of neuroendoscopy, even for neurosurgeons well
      accustomed to the use of microscopes. To decrease the slope of the learning curve
      of residents during their training and reduce complications of procedures, most
      neurosurgery training programs around the world have incorporated laboratory or
      dissection programs in their curricula. Preconference workshops held during
      annual meetings are also an excellent tool to aid in the transition of surgeons
      from being a resident under the umbrella of an attending neurosurgeon to being a
      neurosurgeon able to operate independently and with confidence. In this "tech
      savvy era," various cadaver or synthetic models are readily available for
      endoscopy training in a virtually simulated environment. In accord with the
      results of a surveys conducted by individual groups and societies, the authors
      firmly believe that incorporation of endoscopy in the neurosurgical curriculum
      would add a new dimension to the existing protocol. There is an urgent need for
      dedicated endoscopy training programs similar to postresidency fellowships in
      addition to translational research and establishment of dedicated societies to
      formulate guidelines for such research and monitor its progress.

PMID- 22381836
TI  - Anatomic skull base education using advanced neuroimaging techniques.
AB  - OBJECTIVE: The goal of the present article was to describe our dissection
      training system applied to a variety of endoscopic endonasal approaches. It
      allows one to perform a 3D virtual dissection of the desired approach and to
      analyze and quantify critical surgical measurements. METHODS: All the human
      cadaveric heads were dissected at the Laboratory of Surgical Neuro-Anatomy (LSNA)
      of the University of Barcelona (Spain). The model surgical training protocol was
      designed as follows: 1) virtual dissection of the selected approach using our
      dissection training 3D model; 2) preliminary exploration of each specimen using a
      second 3D model based on a preoperative computed tomographic scan; 3) cadaveric
      anatomic dissection with the aid of a neuronavigation system; and 4)
      quantification and analysis of the collected data. RESULTS: The virtual
      dissection of the selected approach, preliminary exploration of each specimen, a
      real laboratory dissection experience, and finally, the analysis of data
      retrieved during the dissection step was a complete method for training manual
      dexterity and hand-eye coordination and to improve the general knowledge of
      surgical approaches. CONCLUSIONS: The present model results are found to be
      effective, providing a valuable representation of the surgical anatomy as well as
      a 3D visual feedback, thus improving study, design, and execution in a variety of
      approaches. Such a system can also be developed as a preoperative planning tool
      that will allow the neurosurgeon to practice and manipulate 3D representations of
      the critical anatomic landmarks involved in the endoscopic endonasal approaches
      to the skull base.

PMID- 22381837
TI  - Neuronavigational neuroendoscopy--to be or not to be? An international pilot
      questionnaire-based study.
AB  - OBJECTIVE: The almost age-old neuroendoscopy (NE) and neuronavigation (NN) in its
      twenties independently and indisputably have proved their high value as
      neurosurgical armamentarium and became even indispensable in some pathologies.
      However, nowadays the effectiveness of their simultaneous and combined
      application still is a matter of debate. The purpose of our pilot international,
      questionnaire-based survey was to assess the position of the opinion leaders in
      the field of neuroendoscopy worldwide toward the neuronavigational neuroendoscopy
      (NNNE). METHODS: Within 3 months, a questionnaire with 17 questions was emailed
      repeatedly to 55 leading academic neuroendoscopic neurosurgeons from 50
      institutions in 24 countries. The questionnaire covered aspects of personal and
      institutional experience in NE, NN, and NNNE, the most frequently treated
      pathologies by NNNE as well as inquiring the neurosurgeons' opinion for the
      importance and future of NNNE. RESULTS: Forty-one questionnaires were returned
      (response rate = 74.6%). Six questionnaires were excluded because of incomplete
      or incorrect answers, leaving in the survey 35 respondents from 35 institutions
      in 18 countries. The less experienced neurosurgeons rely in higher degree on
      NNNE. Most frequently, NNNE is performed for hydrocephalus (procedures other than
      third ventriculostomy), transsphenoidal surgery, tumor biopsy, and cyst
      fenestration. Regardless their neurosurgical and NE experience, more than 75% of
      the respondents state that NNNE extends the range of neuroendoscopic procedures
      in their neurosurgical departments. CONCLUSION: NNNE represents a valuable
      operative technique with excellent future prospects. NNNE extends the range of
      neuroendoscopic procedures, transforming some number of patients from
      "nonoperable" neuroendoscopically to suitable for neuroendoscopy.

PMID- 22381838
TI  - Endoscopic management of intracerebral hemorrhage.
AB  - OBJECTIVES: Massive intracerebral and intraventricular hemorrhages require
      aggressive and rapid management to decrease intracranial hypertension. The amount
      of intraventricular blood is a strong prognostic predictor, and its fast removal
      is a priority. Neuroendoscopy may offer some advantages over more traditional
      surgical approaches. METHODS: All relevant data described in our experience and
      in publications about minimally invasive treatment of intraventricular and
      intracerebral hemorrhage found through MEDLINE searches and related references
      are reviewed. RESULTS: We described the technical details of neuroendoscopic
      management, highlighting the potential pitfalls and advantages of the techniques.
      CONCLUSION: Early neuroendoscopic surgery is a feasible approach, allowing, in
      most instances, rapid clinical and radiological improvement.

PMID- 22381839
TI  - The keyhole concept in neurosurgery.
AB  - OBJECTIVE: Improvements in preoperative diagnostic imaging as well as in
      microsurgical techniques significantly advanced the development of transcranial
      neurosurgery, allowing the treatment of complicated diseases through smaller and
      more specific approaches. METHODS: In this article, authors overviewed their
      experience in transcranial endoscope-assisted microsurgery, using limited-sized
      keyhole craniotomies. Over a 10-year period, authors treated more than 3000
      patients according to the transcranial endoscope-assisted microsurgery concept,
      advanced by the pioneer of minimally invasive neurosurgery, Axel Perneczky.
      RESULTS AND CONCLUSION: In all cases, meticulous preoperative planning was done
      for determining the site, size, and optimal placement of the craniotomy as well
      as the trajectory toward the surgical target. Most importantly, the surgical
      approach was performed either completely or at least under permanent presence of
      the responsible senior surgeon from the moment of patient positioning until wound
      closure. The minimally invasive keyhole approaches allowed safe intraoperative
      control and adequate dealing with intracranial lesions. Essential preconditions
      for keyhole surgery were 1) careful selection of cases, 2) accurate preoperative
      planning, 3) placement of the craniotomy tailored to the individual case, and 4)
      intraoperative use of transcranial endoscope-assisted microsurgery techniques.
      Advantages of intraoperative endoscopic visualization were increased light
      intensity, extended viewing angle, and clear depiction of details even in hidden
      parts of the surgical field.

PMID- 22381840
TI  - Intraventricular tumors.
AB  - OBJECTIVE: To describe the neuroendoscopic technique to deal with
      intraventricular tumors. METHODS: Details of the endoscopic approach to
      intraventricular tumors of the lateral, third, and fourth ventricle are
      presented. RESULTS: Intraventricular tumors are ideal indications for
      neuroendoscopic surgery. They often cause cerebrospinal fluid (CSF) pathway
      obstruction, resulting in ventricular dilation, which provides sufficient space
      for maneuvering with the endoscope. The general principle of the endoscopic
      removal of intraventricular tumors is interruption of the blood supply to the
      tumor and subsequent tumor debulking. In general, a piecemeal resection is
      performed; however, in some tumors, it is possible to detach the lesion from the
      surrounding brain tissue and remove it in toto. In unilateral hydrocephalus
      caused by obstruction of one foramen of Monro, the burr hole is placed more
      laterally to get good access to the foramen for biopsy and to the septum for
      septostomy. When the tumor arises in the anterior part of the third ventricle,
      the burr hole is made at the coronal suture. When the tumor is located in the
      posterior part, the entry point is selected more anteriorly in order to pass the
      foramen of Monro in a straight line. In pineal region tumors, which cause
      occlusive hydrocephalus due to aqueductal compression, third ventriculostomy as
      well as tumor biopsy are required. CONCLUSION: Intraventricular tumors and
      related CSF pathway obstructions can be safely and effectively treated with
      endoscopic techniques. Small tumors may be totally removed via a ventriculoscope.

PMID- 22381841
TI  - Endoneurosurgical resection of intraventricular and intraparenchymal lesions
      using the port technique.
AB  - OBJECTIVE: Deep-seated intraventricular and intraparenchymal lesions have
      traditionally been resected via transcortical routes, often requiring the use of
      retractors to maintain the corridor created to reach the lesion and proceed with
      a bimanual microsurgical resection. A transparent cylindrical conduit (port) has
      been developed to resect deep-seated lesions using the endoscope or, more
      recently, Video Telescopic Operating Microscopy (VTOM) for visualization. We
      describe the surgical technique of the port technique and discuss the evolution
      of the concept of intraaxial brain surgery performed through a conduit. METHODS:
      Detailed description of the ventriculoport and brainport technique with
      illustrative cases. RESULTS: Results of intraventricular and intraparenchymal
      port surgery have been published and document the feasibility and safety of this
      technique. Over the years, the technique has been improved. The port technique
      offers numerous potential advantages, including: 1) minimizing white matter
      disruption as the tip design minimizes the risk of fascicles injury during
      cannulation; 2) ensuring stability as the rigidity prevents inadvertent expansion
      of the initial diameter of the corticectomy and white fiber tract dissection
      throughout surgery; 3) protecting the surrounding tissues against iatrogenic
      injuries caused by instrument entry and reentry; 4) affording constant
      visualization of the tissue traversed given the transparent conduit design; 5)
      enabling homogeneous radial dispersion of the pressure on the surrounding tissue
      to minimize injury. CONCLUSION: The port technique is an option for resection of
      intraventricular and intraparenchymal lesions. Additional studies are required to
      assess its impact on adjacent cerebral tissue morphology, blood flow, and
      metabolism. Quality-of-life assessments are also needed. High-definition fiber
      tracking, new visualization techniques (VTOM), and new instrumentation will add
      to the progress of endoscopic port surgery. We have already seen a significant
      evolution of the technology even since the preparation of this article.

PMID- 22381842
TI  - Endoscopic treatment of intraventricular cystic tumors.
AB  - OBJECTIVE: Intraventricular cystic tumors constitute a surgical challenge,
      because of their deep location and the histologically benign nature of most of
      them. We aim to present concisely, yet comprehensively, the role of
      neuroendoscopy in the treatment of intraventricular cystic tumors. METHODS: A
      literature review searching for applications of endoscopy in the treatment of
      intraventricular cystic tumors is presented. Our experience is added to the
      presented data. In controversial issues, a comparison is made with traditional
      treatment methods. RESULTS: Intraventricular endoscopy has been successfully used
      in the treatment of the whole range of intraventricular cystic tumors. The most
      common indication is the treatment of colloid cysts. In the treatment of colloid
      cysts, a comparison with microsurgical techniques showed that endoscopy is
      advantageous in regard to operative morbidity and postoperative shunt dependency
      but is associated with a slightly higher recurrence rate. CONCLUSION:
      Intraventricular endoscopy has emerged as a viable option in the treatment of
      intraventricular cystic tumors.

PMID- 22381843
TI  - Pineal region tumors: simultaneous endoscopic third ventriculostomy and tumor
      biopsy.
AB  - OBJECTIVE: Advances in neuroendoscopy have accommodated the development of
      intraventricular techniques that enhance the management of multiple disease
      processes. Tumors of the pineal region are amenable to endoscopic management in
      that they are accessible through the third ventricle and commonly cause
      hydrocephalus that can be alleviated by endoscopic third ventriculostomy (ETV).
      We describe the indications for and procedure of simultaneous ETV and biopsy of
      pineal region tumors, as well as the clinical features favoring different
      approaches to this procedure. METHODS: The current literature on endoscopic
      management of pineal region tumors and the senior author's clinic experience with
      current techniques are reviewed. RESULTS: Simultaneous tumor biopsy with ETV
      following initial evaluation with tumor markers and imaging can be accomplished
      using a single or dual entry approach. The choice of approach is dependent on
      multiple clinical factors including massa intermedia size, goals of surgery,
      degree of hydrocephalus, and the relationship between the tumor and massa
      intermedia. CONCLUSIONS: Simultaneous ETV and tumor biopsy is a valuable
      technique that can be used to manage hydrocephalus and establish diagnosis in
      patients with newly diagnosed pineal region tumors, potentially avoiding
      traditional craniotomy and ventriculoperitoneal shunt placement. It is favored as
      an early step in the management of patients with marker-negative tumors.

PMID- 22381844
TI  - Neurocysticercosis.
AB  - OBJECTIVE: Neurocysticercosis is the most common parasitosis of the central
      nervous system. Many forms, especially those inside the ventricles, carry a poor
      prognosis. Drug therapy is far from ideal. METHODS: We propose and comment on the
      use of the endoscope to remove cysts, treat hydrocephalus, and to perform
      membrane fenestration as a way to simplify treatment. RESULTS: Many patients,
      especially those with obstructive forms, benefit from the adjunctive use of
      neuroendoscopy. CONCLUSIONS: Neurocysticercosis treatment remains challenging and
      multimodal. Endoscopes can be helpful in this setting.

PMID- 22381845
TI  - Endoscopic third ventriculostomy and posterior fossa tumors.
AB  - BACKGROUND: The management of hydrocephalus associated with a posterior fossa
      tumor is debated. Some authors emphasize the advantages of an immediate tumor
      removal that may normalize the cerebrospinal fluid (CSF) dynamics. However, in
      clinical practice, the mere excision of the lesion has been demonstrated to be
      accompanied by a persisting hydrocephalus in about one third of the cases.
      Preoperative endoscopic third ventriculostomy (ETV) offers several advantages. It
      may control the intracranial pressure (ICP), avoid the necessity of an emergency
      procedure, allow appropriate scheduling of the operation for tumor removal, and
      eliminate the risks related to the presence of an external drainage. The
      procedure also reduces the incidence of postoperative hydrocephalus. A final
      advantage, more difficult to weight, but obvious to the neurosurgeon, is the
      possibility to remove the lesion with a relaxed brain and normal ICP. In the
      postoperative phase, ETV can be used in case of persisting hydrocephalus, both in
      patients who underwent only the excision of the tumor and in those whose
      preoperative ETV failed as a consequence of intraventricular bleeding with
      secondary closure of the stoma (redoETV). The main advantage of postoperative ETV
      is that the procedure is carried out only in case of persisting hydrocephalus;
      its use is consequently more selective than preoperative ETV. The disadvantage
      consists in the common use of an external CSF drainage in the first few
      postoperative days, which is necessary to control the pressure and for ruling out
      those cases that reach a spontaneous cure of the hydrocephalus. METHODS: The
      authors review the criteria for patient selection and the results of ETV
      performed in case of hydrocephalus secondary to a posterior fossa tumor. RESULTS
      AND CONCLUSIONS: Preoperative ETV constitutes an effective procedure for
      controlling the hydrocephalus associated with posterior fossa tumors. It might
      lower the rate of persistent postoperative hydrocephalus and result in a short
      hospital stay. Low rates of patients requiring an extrathecal-CSF shunt device
      are also reported by authors who utilize ETV postoperatively. As, however, the
      assessment of the persistent hydrocephalus in these children is based on
      prolonged ICP monitoring through an external CSF drainage, their results are
      weighted by a major risk of infective complications and longer hospital stay.

PMID- 22381846
TI  - Third ventriculostomy and fourth ventricle outlets obstruction.
AB  - A dilated fourth ventricle due to outlet obstruction is a clinical-radiologic
      entity with symptoms similar to those of a posterior fossa space-occupying
      lesion. Indeed, blockage of the foramina of Luschka and Magendie and of the
      aqueduct results in a "trapped" fourth ventricle. Continued cerebrospinal fluid
      (CSF) production within the fourth ventricle leads to cystic dilatation of the
      fourth ventricle. We could not, until now, understand the phenomenon, mainly on
      exploring endoscopically the permeability of the whole aqueduct. In adults, we
      call this condition the functional trapped fourth ventricle because in none of
      our cases have we found physical obstruction of CSF flow. Third ventricle-fourth
      ventriculostomy is by far the most frequently used technique for cannulation of
      the aqueduct in a trapped fourth ventricle. In our reported cases, we have
      introduced a silicone tube stent from below after accessing the fourth ventricle
      through a small suboccipital craniectomy, ascending it on the aqueduct in order
      to reach the third ventricle. Management of this infrequently isolated fourth
      ventricle, but communicated with the rest of ventricular system, remains a
      challenge for neurosurgeons. Lack of knowledge of the pathophysiology makes it
      difficult to treat a problem that we do not understand.

PMID- 22381847
TI  - Third ventriculostomy in shunt malfunction.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) is the treatment of choice for
      noncommunicating hydrocephalus. In the last decade, its routine use also has
      taken place in patients who have previously undergone shunt placement (secondary
      ETV). METHODS: This study reviews the specific anatomy of the ventricular system
      in patients presenting with shunt malfunction, the criteria for patient
      selection, and the results of ETV performed as an alternative to shunt revision
      in cases of shunt malfunction or infection. RESULTS: The success rate of
      secondary ETV in well-selected cases is not different from that of primary ETV;
      it should be reasonable to offer all patients with blocked shunts and suitable
      anatomy indicating an obstructive cause the opportunity for shunt independence
      regardless of the original cause of the hydrocephalus. CONCLUSIONS: Shunt
      infection should not be considered a contraindication to ETV, even if the success
      rate may be lower. Considering the higher complication rate and higher risk of
      intraoperative failure, secondary ETV should be performed by expert
      neuroendoscopists.

PMID- 22381848
TI  - Management of hydrocephalus around the world.
AB  - OBJECTIVE: The objective of this study is to review the management of
      hydrocephalus and, in particular, how different economic and social conditions
      affect its treatment around the world. METHODS: The main techniques for the
      surgical treatment and the management of hydrocephalus have been retraced through
      a brief historical overview up to the present day. RESULTS: During the last
      century, continuous technological progress has favored the diffusion of expensive
      and sophisticated shunt systems. On the other hand, the advent of minimally
      invasive endoscopic techniques, such as endoscopic third ventriculostomy, seems
      to represent a valid route for attempting a natural cerebrospinal fluid
      diversion, thus avoiding complications related to shunt failure. CONCLUSIONS: The
      management of hydrocephalus around the world is still widely debated. However,
      definition of proper indications and adequate training in neuroendoscopic
      techniques seem to represent the preeminent trend for new generations of
      neurosurgeons.

PMID- 22381849
TI  - Neuroendoscopy in the youngest age group.
AB  - OBJECTIVES: The aim of this report is to review current data on the role of
      neuroendoscopy in infants. Specific emphasis will be given to the International
      Infant Hydrocephalus Study (IIHS). Previous studies, available information, and
      future directions are discussed. METHODS: The IIHS is a major international
      endeavor comparing the results of endoscopic third ventriculostomy (ETV) to
      ventriculoperitoneal shunting in infants younger than 2 years of age. It is a
      prospective, randomized study, with a "parental preference" option, that recruits
      infants with aqueductal stenosis without a history of prematurity or other
      associated brain anomalies. The primary outcome measure is neurocognitive outcome
      at 5 years of age. In addition to IIHS data, we also looked at results of
      neuroendoscopy in infants with other indications, such as fourth ventricular
      outlet obstruction, Dandy Walker syndrome, etc. RESULTS: The IIHS study includes
      more than 40 centers on all continents. To date, we have recruited more than 150
      infants to the study. At this point we can only release limited data, namely that
      the complication rates are similar between the two arms. More patients are needed
      to finalize the study, with an endpoint of 250 children. CONCLUSIONS:
      Neuroendoscopy in infants can be performed with reasonable morbidity. The
      preferred indications in infants are still not totally refined, especially vis-a
      vis shunting procedures. More international, multicenter efforts are required to
      clarify these points.

PMID- 22381850
TI  - Endoscopic challenges and applications in tuberculous meningitis.
AB  - Endoscopy for hydrocephalus caused by infectious diseases presents clear
      challenges to the surgeon. Hydrocephalus caused by tuberculous meningitis is a
      good model to explore many of the issues that should be considered in the
      management of these patients. Tuberculous hydrocephalus may be communicating or
      noncommunicating management options include medical treatment (for communicating
      hydrocephalus), ventriculoperitoneal shunting, and endoscopic third
      ventriculostomy. No guidelines exist currently, and therefore management
      protocols are specific to each center. Because brain ischemia attributable to
      vasculitis is common in these patients, optimal treatment of intracranial
      pressure (ICP) is even more important than usual, and this has implications for
      the management decisions. Effective treatment of these patients should lead to
      normalization of ICP and resolution of the hydrocephalus, rather than merely
      avoiding extreme elevations of ICP. However, this also must be weighed against
      the surgical and long-term complications associated with the procedures used.
      There are specific endoscopic challenges that occur as the result of abnormal
      anatomy and the fact that hydrocephalus presents during the acute phase of the
      disease, rather than being postinfectious. In this article we examine the
      arguments for various therapeutic approaches and discuss the gathering experience
      in the literature about endoscopy in tuberculous meningitis in the context of
      overall management options.

PMID- 22381851
TI  - Mobile endoscopy: a treatment and training model for childhood hydrocephalus.
AB  - BACKGROUND: Hydrocephalus, largely a disease of poverty in many developing
      regions such as Sub-Saharan Africa, becomes even more challenging to treat
      because of lack of trained neurosurgical personnel, inadequately equipped public
      health care facilities, meager resource allocation, high rates of neonatal
      infection, difficulty of access to tertiary care hospitals able to treat
      hydrocephalus, and high complication rates in patients who are able to access and
      receive shunting procedures. Furthermore, conventional methods of training of
      neurosurgeons and nursing staff to become proficient in neuroendoscopic
      procedures involve a lengthy period of training, often at specialized centers in
      Western or local Western-style institutions. METHODS: The novel approach promoted
      by volunteer neurosurgical teams from Neurosurgery Education Development
      Foundation is described, and its potential role in successfully providing
      neuroendoscopic ventriculostomy at hospitals in regional sites away from main
      referral tertiary hospitals is outlined. The impact on the training of local
      neurosurgical specialists and residents in training as well as nursing staff is
      highlighted. RESULTS: With the use of a single portable neuroendoscopy system and
      a versatile free-hand, single-operator neuroendoscope, this outreach, mobile, and
      readily portable model has been successfully used to perform more than 250
      procedures in 21 different hospital sites around seven different countries in two
      continents. The local courses have imparted hands-on training to 62 neurosurgeons
      and trainee residents and a further 110 operating room nurses at these 21
      institutions. CONCLUSIONS: Neuroendoscopy is not only a priority surgical tool
      for East Africa. It offers a medical philosophy as an application that serves as
      an art and a science dedicated to the development of a complex surgical
      specialty: neurosurgery.

PMID- 22381852
TI  - Incidental consequences of antihelmintic treatment in the central nervous system.
AB  - BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic infection in
      the central nervous system and the most common cause of acquired neurological
      symptoms in young adults living in developing countries. Many "asymptomatic"
      patients begin experiencing neurological symptoms after the use of antiparasitic
      drugs for gastrointestinal treatment. Patients who are previously diagnosed with
      NCC require special care during cysticidal treatment because of the inflammatory
      effects caused by the interaction between the drug, the parasite, and the host.
      CASE DESCRIPTION: Of a series of 46 cases, we selected five patients with a
      history of being "asymptomatic" and who began experiencing neurologic symptoms
      after the use of albendazole, which led to a diagnosis of cysticercosis. Another
      case of the patient, who already had been diagnosed of ventricular cysticercosis,
      was given a drug treatment without consulting the neurosurgeon and had a fatal
      outcome attributable to secondary meningoencephalitis. RESULTS: In the first five
      cases, with new neurological symptoms after antihelmintic treatment, the self
      prescription is remarkable. The symptoms appear between the third and fifth day
      of treatment. All of them had a clinical course without complications. Only two
      cases minimally invasive techniques were required. The case who had been already
      diagnosed developed meningoencephalitis and died after eight days of
      antihelmintic treatment. CONCLUSIONS: Anthelminthic drug treatment requires
      tailor-based prescription considering risk-benefit ratio with the drug-parasite
      host interaction in mind. Treatment is not harmless so patients have to be
      closely watched. In select cases, medical treatment cannot replace surgical
      procedures, which can be the primary approach with drug treatment as a
      complement.

PMID- 22381853
TI  - Endoscopic endonasal transmaxillary approach and endoscopic sublabial
      transmaxillary approach: surgical decision-making and implications of the
      nasolacrimal duct.
AB  - BACKGROUND: The nasolacrimal duct resides in the wall of the medial nasal cavity
      and influences minimal access endoscopic transmaxillary approaches to the lateral
      skull base. We describe an algorithm for surgical approach selection on the basis
      of the relationship of the target lesion to a line drawn from the anterior nasal
      SEptum through the Nasolacrimal Duct to the lesion (i.e., SEND line). METHODS: We
      use the SEND line to estimate the lateral extent in the endonasal middle meatal
      transmaxillary approach, where the surgeon has good surgical freedom without the
      use of angled instruments and endoscopes. Lesions with an epicenter lateral to
      the SEND line were addressed through a sublabial anterior antrostomy
      transmaxillary corridor. Tumors with a more medially located epicenter, such as
      those involving the lateral sphenoid sinus and pterygoid plates, were addressed
      through the endonasal middle meatal corridor. Extensive tumors involving both
      domains were addressed through a combination approach. RESULTS: We describe three
      instructive cases in which the approach selection was determined in part by
      preoperative assessment of the location of the tumor relative to the SEND line.
      CONCLUSIONS: The endoscopic sublabial transmaxillary and endoscopic endonasal
      middle meatal transmaxillary approaches are complementary corridors to the
      anterior skull base that can be used independently or in combination. The
      location of the target lesion relative to the SEND line as determined on
      preoperative imaging can serve as a guide for surgical decision making.

PMID- 22381854
TI  - Suprasellar hamartoma and arachnoid cyst.
AB  - OBJECTIVE: The differential diagnosis for suprasellar masses includes a variety
      of pathologies, ranging from stable and benign lesions to aggressive and
      malignant ones. We report a case of a suprasellar hamartoma associated with an
      arachnoid cyst and review the literature surrounding the topic. CASE DESCRIPTION:
      A 32-year-old man who presented with headaches and nonspecific vision loss was
      found to have a cystic, calcified, and minimally contrast enhancing lesion of the
      suprasellar region. Intraoperative inspection revealed a discrete mass in the
      right side of suprasellar region that resembled normal brain completely enveloped
      by the basal arachnoid membranes including the membrane of Lillequist and was not
      connected to the brain. Fenestration and exploration of the cystic portion
      demonstrated a simple arachnoid cyst filled with what appeared to be
      cerebrospinal fluid. Given the adherence of the lesion to numerous perforating
      arteries arising from the posterior communicating artery, a biopsy with
      intraoperative confirmation was taken. Pathology was consistent with neuroglial
      tissue without evidence of neoplasia. CONCLUSIONS: To our knowledge this is only
      the third case of an isolated suprasellar hamartoma described in the literature
      and the first of its kind to be associated with an arachnoid cyst.

PMID- 22381855
TI  - Stereotactic radiosurgery for trigeminal pain secondary to benign skull base
      tumors.
AB  - OBJECTIVE: To assess the outcome of stereotactic radiosurgery (SRS) for patients
      with benign skull base tumors and trigeminal-related facial pain. METHODS: We
      undertook a retrospective review of 31 consecutive patients (25 women, 6 men)
      with benign skull base tumors and trigeminal pain who underwent SRS between 1991
      and 2008. The tumors included 17 posterior fossa meningiomas, 9 cavernous sinus
      meningiomas, and 5 trigeminal schwannomas. The median patient age was 62 years
      (range, 17-81 years). In all cases the tumor was the primary target for SRS. The
      median follow-up after SRS was 50 months (range, 12-184 months). RESULTS: The
      actuarial tumor control rate after SRS was 95% at both 3 years and 5 years.
      Eighteen patients (58%) initially achieved complete resolution of trigeminal
      pain. Higher maximum dose was associated with initial complete pain resolution on
      a multivariate analysis. However, 7 patients had recurrent pain during follow-up.
      At last follow-up, only 7 patients (23%) remained pain-free off medications.
      Further treatment in addition to medical therapy was required for 6 patients
      (19%). CONCLUSION: Although SRS offers excellent radiographic tumor control for
      benign skull base tumors, durable relief of tumor-related trigeminal pain without
      medication was noted in only one-fourth of patients at last follow-up.

PMID- 22381856
TI  - Traumatic (type II) odontoid fracture with transverse atlantal ligament injury: a
      controversial event.
AB  - OBJECTIVE: Traumatic (Type II) odontoid fractures are very common injuries.
      Nevertheless, their connection with transverse atlantal ligament injury is
      controversial and poorly defined. The aim of this study is to report a single
      case of traumatic (type II) odontoid fracture with transverse atlantal ligament
      injury and to critically analyze the role of ligaments and membranes together
      with neuroradiological tools in the management of craniovertebral junction
      traumatized patients. METHODS: We report 27 consecutive cases of traumatic (type
      II) odontoid fractures who underwent magnetic resonance imaging (MRI) in the
      acute phase injury (<72 hours), focusing our attention on the transverse atlantal
      ligament. RESULTS: One patient (3.7%) demonstrated a transverse atlantal ligament
      injury on MRI. The patient underwent surgery. CONCLUSIONS: Traumatic (type II)
      odontoid fracture with transverse atlantal ligament avulsion can be considered an
      unusual event. It is our opinion that the routine use of MRI for all patients
      with type II odontoid fracture could be unjustified in clinical practice. Strict
      clinical surveillance of all patients managed conservatively and the use of MRI
      in selected cases could be a reasonable management option.

PMID- 22381857
TI  - Minimally invasive posterior atlantoaxial fusion: a cadaveric and clinical
      feasibility study.
AB  - OBJECTIVE: Minimally invasive surgical (MIS) techniques have several potential
      advantages for the patient over open techniques, including decreased loss of
      blood, postoperative pain, and recovery time. We aimed to demonstrate
      atlantoaxial fusion by using the MIS techniques, shown previously in only two
      reports. A smaller operating corridor with MIS may increase difficulty of
      instrumentation placement and risk of instrumentation-related complications.
      METHODS: Five cadaveric specimens were studied presurgically with computed
      tomography (CT) to determine bony anatomy, vertebral artery course, and the
      trajectory for C1/C2 screw placement. Four specimens had adequate C2 pedicle
      sizes to accommodate screw placement. Specimens were used to perform C1-2
      instrumentation through minimal access tubular retractors. After procedures,
      specimens were re-examined with CT to assess accuracy of MIS C1-2 screw
      placement. RESULTS: Through minimal access expandable tubular retractors, C1
      lateral mass and C2 pedicle screws were placed in all four specimens.
      Postinstrumentation CT analysis demonstrated no violation of the foramen
      transversarium in all cases. There was one grade 1 medial breach from C1 lateral
      mass screw placement. Two patients with type-2 odontoid fractures were treated
      with MIS C1-2 fusion with follow-up 4-24 months. Average operating time was 3.5
      hours, and average surgical blood loss was 125 mL. Both cases were examined with
      CT scan postsurgically, and there were no bony breaches with screw placement.
      Both patients remained neurologically intact postoperatively, with significant
      improvement revealed in pain scores. Follow-up imaging at two years demonstrated
      union of odontoid fracture. CONCLUSIONS: Minimally invasive atlantoaxial fixation
      is feasible and safe. Preoperative CT is paramount for preoperative evaluation of
      the vertebral artery anatomy in relation to C1/2 vertebra.

PMID- 22381859
TI  - Standardizing the evaluation of scientific and academic performance in
      neurosurgery--critical review of the "h" index and its variants.
AB  - Assessing the academic impact and output of scientists and physicians is
      essential to the academic promotion process and has largely depended on peer
      review. The inherent subjectivity of peer review, however, has led to an interest
      to incorporate objective measures into more established methods of academic
      assessment and promotion. Journal impact factor has been used to add objectivity
      to the process but this index alone does not capture all aspects of academic
      impact and achievement. The "h" index and its variants have been designed to
      compensate for these shortcomings, and have been successfully used in the fields
      of physics, mathematics, and biology, and more recently in medicine. Leaders in
      academic neurosurgery should be aware of the advantages offered by each of these
      indices, as well as of their individual shortcomings, to be able to efficiently
      use them to refine the peer-review process. This review critically analyzes
      indices that are currently available to evaluate the academic impact of
      scientists and physicians. These indices include the total citation count, the
      total number of papers, the impact factor, as well as the "h" index with eight of
      its most common variants. The analysis focuses on their use in the field of
      academic neurosurgery, and discusses means to implement them in current review
      processes. 

PMID- 22381858
TI  - Dural arteriovenous fistulas: a review of the literature and a presentation of a
      single institution's experience.
AB  - OBJECTIVE: Dural arteriovenous fistulas (DAVFs) are arteriovenous shunts from a
      dural arterial supply to a dural venous channel, typically supplied by
      pachymeningeal arteries and located near a major venous sinus. A retrospective
      review was conducted to present the results of endovascular obliteration of
      DAVFs, with particular emphasis of newer liquid embolic agents, including Onyx-18
      (MV3, Irvine, California, USA). METHODS: A review of the literature was
      performed, and a presentation of the number of treatments, complications, and
      outcomes is included here. The number of arterial embolizations and need for
      transvenous embolization, open surgery, and radiosurgery was assessed as well as
      normalization of retrograde cortical venous drainage. RESULTS: Thirty-nine
      patients (22 men and 17 women) underwent endovascular treatment of DAVFs at our
      institution from 2001 to 2009. Ages ranged from 39 to 71 years (mean, 48 years).
      Seventy-nine percent of patients had retrograde cortical venous drainage. The
      average number of embolizations in all patients was 2.1. Twelve patients
      underwent 40 embolization treatments with Onyx, with an obliteration rate of 75%
      and cortical venous drainage obliteration rate of 85%. Seventy-one percent
      (28/39) of patients had complete treatment of the fistula: 21 by purely
      endovascular treatment and 7 with endovascular therapy followed by craniotomy, as
      well as seven patients who underwent stereotactic radiosurgery after
      embolization. CONCLUSIONS: Endovascular management of DAVFs is a safe and
      effective method of treating these complex lesions.

PMID- 22381860
TI  - The Arab spring in Tunisia: urgent plea for a public health system (r)evolution.

PMID- 22381861
TI  - Cervical spinal brucellosis: a diagnostic and surgical challenge.

PMID- 22381862
TI  - Noxious blood or faulty vessels--the mystery of vasospasm.

PMID- 22381863
TI  - Vertebral artery compression and occlusion syndrome in the cervical spine and the
      foramen magnum.

PMID- 22381864
TI  - Is 'self-to-self' bone graft ideal for bone fusion after craniovertebral
      stabilization?

PMID- 22381865
TI  - Venous thromboembolism in spine surgery.

PMID- 22381866
TI  - Surgery of spinal tumors without complications does not exist.

PMID- 22381867
TI  - Rathke's cleft cysts: unanswered questions.

PMID- 22381868
TI  - The long-term outcome predictors of pure microvascular decompression for primary
      trigeminal neuralgia.
AB  - OBJECTIVE: The aim of this study is to provide credible and comparable evidence
      on the efficacy and safety of pure microvascular decompression (MVD) for primary
      trigeminal neuralgia (TN), and also to find out the possible prognostic factors
      of excellent long-term outcome after the surgery. METHODS: A prospective cohort
      study was conducted, involving the patients who met the diagnostic criteria of
      primary TN (both typical and atypical). The cohort patients underwent pure MVD,
      and then were followed up by independent neurologists. The possible prognostic
      factors were analyzed by the logistic method. RESULTS: All 154 consecutive
      primary TN patients (98 typical, 56 atypical) underwent pure MVD from January
      2001 to November 2005. The patients were followed up for median 5.6 years (10
      lost in 5 years). Respective initial and 5-year's complete pain-free without
      medication (Barrow Neurological Institute pain score, I) rates were 84% and 72%
      for total primary TN, 87% and 80% for typical TN, and 79% and 54% for atypical
      TN. The Kaplan-Meier survival curves of 5 years demonstrated different long-term
      outcomes in different groups (typical TN vs. atypical TN). The typical symptoms
      (odds ratio [OR], 2.776), preoperative magnetic resonance indicating vessel
      compression (OR, 2.950), and obvious vessel compression found during operation
      (OR, 3.219) were proved to have a positive effect on long-term pain relief
      without medication. CONCLUSIONS: This is a perspective cohort study of pure MVD,
      which confirms the long-term effectiveness and safety of the surgery for primary
      TN. Patients with typical symptoms, positive magnetic resonance findings, or
      obvious vessel compressions might have better long-term prognosis.

PMID- 22381869
TI  - Use of a spin-labeled cerebrospinal fluid magnetic resonance imaging technique to
      demonstrate successful endoscopic fenestration of an enlarging symptomatic cavum
      septi pellucidi.
AB  - OBJECTIVE: The aim of this study was to noninvasively visualize whether
      cerebrospinal fluid (CSF) compartments are in communication. CASE DESCRIPTION: An
      enlarging cavum septi pellucidi (CSP) produced progressive hydrocephalus
      following subarachnoid hemorrhage. We questioned what were the dynamics of CSF
      flow that led to enlargement of the CSP. CONCLUSION: With this case report, we
      show the usefulness of a newly described magnetic resonance imaging time-spatial
      labeling inversion pulse technique to establish that an enlarging CSP was the
      cause of progressive hydrocephalus and that the hydrocephalus was successfully
      endoscopically treated when the CSP was fenestrated into the ventricular system,
      establishing communication between the two CSF compartments.

PMID- 22381870
TI  - Rationale for treating unruptured intracranial aneurysms: actuarial analysis of
      natural history risk versus treatment risk for coiling or clipping based on
      14,050 patients in the Nationwide Inpatient Sample database.
AB  - OBJECTIVE: The treatment of small unruptured intracranial aneurysms has been
      questioned based on the results of the International Study of Unruptured
      Intracranial Aneurysms. Our objective was to compare natural history rupture risk
      versus treatment risk for coiling and clipping small unruptured aneurysms using
      data in the Nationwide Inpatient Sample database. METHODS: Data for clipping and
      coiling of unruptured aneurysms was collected from the Nationwide Inpatient
      Sample from 2002-2008. Treatment risks were adjusted for age, gender, and medical
      comorbidities. Logistic regression models were used to create curves depicting
      the estimated probability of poor outcome as a function of patient age for
      clipping and coiling. These treatment risk curves were compared against natural
      history actuarial risk curves calculated from four prominent studies. RESULTS:
      There were 14,050 hospitalizations: 7439(53%) coiling; 6611(47%) clipping. For
      patients who underwent coiling or clipping, the mortality rate was 2.17% and
      2.66%, and the morbidity rate was 2.16% and 4.75%, respectively. The adjusted
      risk of poor outcome from clipping and coiling, when modeled against most natural
      history studies, demonstrates a treatment benefit for clipping for patients <70
      years and for coiling patients <81 years. Models using the International Study of
      Unruptured Intracranial Aneurysms data demonstrate a treatment benefit for
      clipping for patients <61 years and for coiling for patients <70 years.
      CONCLUSIONS: Both clipping and coiling of unruptured intracranial aneurysms are
      safe. This analysis demonstrates rationale for clipping small unruptured
      aneurysms in patients <61-70 years and coiling small unruptured aneurysms in
      patients <70-80 years. Treatment beyond these age ranges is associated with
      increased risk of poor outcome.

PMID- 22381871
TI  - Surgical treatment and long-term outcomes of thalamic cavernous malformations.
AB  - OBJECTIVE: Resection of thalamic cavernous malformations (CMs) is controversial.
      The goals of this study were to evaluate the outcome of thalamic CMs after
      surgical resection, assess predictors of prognosis, and review the literature.
      METHODS: The authors used the modified Rankin scale (mRS) to retrospectively
      evaluate the presentation, surgery, and outcomes of 27 consecutive patients who
      underwent thalamic CMs microresection using six different approaches between 1998
      and 2010. RESULTS: Forty-eight hemorrhages occurred in 27 patients (13 men, 14
      women; mean age 33.9 years) with a preoperative mRS score of 2.6 +/- 1.0 and a
      preoperative bleeding rate per patient year of 5.2%. Complete resection was
      achieved in 26 patients (96.3%) without surgical mortality. The postoperative mRS
      score at discharge was 1.9 +/- 1.0. One lesion rebled 1 month after complete
      surgical resection. After a mean follow-up duration of 48.7 +/- 43.2 months, the
      mean mRS score was 1.2 +/- 1.2 and the postoperative rebleeding rate was 0.91%
      per patient-year. With regard to neurological function, 81.5% of patients
      improved, 11.1% stabilized, and 7.4% worsened. Good outcomes (mRS score <=2,
      living independently) were achieved in 21 patients (77.8%). Long-term surgical
      morbidity was observed in five patients (18.2%). A multivariate logistic
      regression analysis identified age (<40 years) as the only predictor of the
      postoperative mRS score (<= 2) (odds ratio, 1.24, 95% confidence interval, 1.02
      1.52; P = 0.035). CONCLUSIONS: To our knowledge, this is the largest case series
      reported in the literature to date. Patients with thalamic CMs can obtain a
      favorable prognosis using microsurgery; an appropriate microsurgical approach
      contributes to an excellent outcome.

PMID- 22381872
TI  - Tibial artery autografts: alternative conduits for high flow cerebral
      revascularizations.
AB  - BACKGROUND: Extracranial-to-intracranial (EC-IC) bypass is a valuable tool in
      treating intracranial diseases requiring flow replacement or parent vessel
      sacrifice. Radial artery grafts (RAGs) and saphenous vein grafts (SVGs) have been
      used as conduits to provide adequate high flow revascularizations. It is a
      therapeutic challenge when these grafts are unavailable. METHODS: All EC-IC high
      flow cerebral revascularizations performed using conduits other than RAGs or SVGs
      were identified from a prospective cerebrovascular registry. These patients were
      retrospectively reviewed for surgical technique, graft patency, graft flow, and
      clinical outcomes. RESULTS: Three patients (all women) underwent EC-IC bypass
      surgery using tibial artery grafts (two anterior tibial artery and one posterior
      tibial artery) because of the nonavailability of RAG or SVG. The two anterior
      tibial artery graft bypasses were patent with good flow at 8 and 3 months. The
      posterior tibial artery graft occluded intraoperatively. None of the patients
      developed vascular complications in the lower extremity due to tibial artery
      harvest. CONCLUSIONS: Tibial arteries are safe, contingent alternatives to
      conventional conduits for performing high flow cerebral revascularizations and
      conduit reconstructions.

PMID- 22381873
TI  - Spinal anatomy in an essential illustrated medical treatise of the late Ottoman
      era.
AB  - OBJECTIVE: The aim of this article is to introduce a great physician of the late
      Ottoman period and his writings on spinal anatomy. METHODS: The article presents
      chapters related to the anatomy of vertebra and the vertebral column in the book
      of Sanizade Ataullah Mehmed, Mir'at al-Abdan fi Tashrih-i A'dai'l-Insan (Mirror
      of the Bodies in the Dissection of the Members of the Human Body). RESULTS: Works
      of Sanizade are viewed as important landmarks in Turkish medical history. Anatomy
      education in Turkey can be divided into four historic periods and the second
      period is called the Sanizade Period (1816-1827). This period leads up to the
      opening of the first modern medical school in Turkey on March 14, 1827.
      CONCLUSIONS: The most important characteristic of Sanizade's work is that it is
      the first illustrated anatomy book printed in the Ottoman Age, and the value of
      the work is shown by Sanizade being one of the originators of medical terms in
      Ottoman Medicine.

PMID- 22381874
TI  - Brain surgery in the bush: adapting techniques and technology to fit the
      developing world.
AB  - The critical shortage of surgical services in many areas of the world has
      profound effects on local communities. Approximately 11% of global disease burden
      can be attributed to causes that are surgically treatable. Efforts have been made
      to recruit professionals from developed nations to compensate for the lack of
      such expertise. However, this practice has created a cycle of dependency on
      foreign-trained physicians and the medical tools they bring. Recognition of this
      problem calls for adaptation of a novel problem-solving approach. This article
      describes techniques and technology available in east Africa that have been
      adapted to allow basic and emergency neurosurgery to be performed in the absence
      of complex medical infrastructure and equipment. Commonplace items found in the
      local environment can be used to emulate more sophisticated instruments, and
      community-specific engineering programs can be developed to provide locally
      produced appropriate technology that promotes independence from Western sources.
      The local economy benefits from much-needed stimulation when these tools are
      created locally, and this allows for readily available replacement and repair.
      More studies are under way to identify problems and implement interventions that
      are realistic and appropriate for these populations.

PMID- 22381875
TI  - A novel endovascular technique for temporary balloon occlusion and permanent
      vessel deconstruction with a single microcatheter.
AB  - OBJECTIVE: To report a novel technique for temporary and permanent vessel
      occlusion with a single microcatheter and investigate its efficacy in
      endovascular management of cerebral aneurysms and invasive head and neck tumors.
      METHODS: A 58-year-old woman with a history of T3N0 squamous cell carcinoma of
      the tongue with extensive surgical resections and radiotherapy presented to the
      emergency department with further wound dehiscence and exposure of the left
      cervical internal carotid artery (ICA). Digital subtraction angiography (DSA) was
      performed with the patient under conscious sedation. An Ascent balloon, 4 mm * 15
      mm, was prepared and introduced into the proximal ICA. While the patient was
      fully awake, temporary balloon occlusion (TBO) was performed for 30 minutes. The
      Ascent balloon was kept inflated. Through the inflated Ascent balloon, coil
      embolization of the proximal ICA was initiated. The interstices of the coils were
      filled with Onyx 18 and Onyx 34 liquid embolic agents (ev3 Neurovascular, Inc,
      Irvine, California, USA). RESULTS: The Ascent balloon can be used as a temporary
      balloon device and as a coil or Onyx embolization device. As a result, fewer
      catheters, guidewires, and balloon inflations and deflations are required for the
      procedure, which is both cost-effective and time-efficient. The combination of
      initial coiling to create a framework for the deconstruction with a liquid
      embolic agent (Onyx) is a safe and efficient technique for vessel deconstruction.
      Flow arrest with proximal balloon occlusion minimizes the risks of distal
      thromboembolic events during embolization. CONCLUSIONS: This novel technique for
      temporary and permanent vessel occlusion with a single microcatheter is both cost
      effective and time-efficient.

PMID- 22381876
TI  - Neurosurgical interventions for spondyloepiphyseal dysplasia congenita: clinical
      presentation and assessment of the literature.
AB  - BACKGROUND: Spondyloepiphyseal dysplasia (SED) is a rare disease that causes
      vertebral abnormalities and short-trunk dwarfism. The two forms of SED are
      congenita and tarda. Each form arises in a genetically distinct fashion and
      manifests with a different set of complications. SED congenita is more severe,
      and patients usually display atlantoaxial instability and odontoid hypoplasia.
      Patients often have various neurologic deficits caused by compression of the
      spinal cord. The region most affected is the craniovertebral junction (CVJ).
      METHODS: A review of the PubMed Database, 1970 to the present, was performed
      using the search term "spondyloepiphyseal dysplasia" and limited to English
      language articles. The search identified 22 articles discussing COL2A1 gene
      mutations and 10 clinical articles describing patients with SED and associated
      spinal abnormalities. RESULTS: Findings from the literature concerning diagnosis,
      presenting symptoms, and intervention taken are discussed. Additionally, a
      patient with a diagnosis of SED congenita who presented with bilateral hand
      numbness is described. The patient underwent a suboccipital craniotomy; posterior
      decompression of the foramen magnum, the arch of C1, and the lamina of C2; and
      instrumented fusion of C1-3 to relieve his symptoms. CONCLUSIONS: In this
      article, the authors survey the current literature surrounding neurosurgical
      interventions and present an algorithm for treatment.

PMID- 22381877
TI  - Beyond therapeutic nihilism? The neurosurgical treatment of intracerebral
      hemorrhage.

PMID- 22381878
TI  - Response to the letter.

PMID- 22381879
TI  - Chronic subdural hematomas.

PMID- 22381880
TI  - The risks of surgery in spontaneous supratentorial intracerebral hemorrhages.

PMID- 22381881
TI  - Will ventralis intermedius deep brain stimulation for tremor be replaced by
      posterior subthalamic area or caudal zona incerta stimulation?

PMID- 22381882
TI  - Current trends in anatomic science.

PMID- 22381883
TI  - Flesh-eating bugs.

PMID- 22381884
TI  - The "SAAFE" neurosurgical sign-out.

PMID- 22381885
TI  - Qualitative and quantitative analysis of dibenzothiophene, its methylated
      homologues, and benzonaphthothiophenes in crude oils, coal, and sediment
      extracts.
AB  - Polycyclic aromatic sulfur heterocyclics (PASHs) consist mainly of thiophene
      class compounds, and are the most important organosulfur compounds in crude oils
      and sediment extracts. Dibenzothiophene (DBT) and its methylated homologues were
      identified on mass chromatograms by comparison with retention indices published
      in the literature. Some isomers of dimethyldibenzothiophene and
      trimethyldibenzothiophene that were tentatively identified in previous reports
      have been determined here by comparison with calculated retention indices and
      taking the substitution pattern of the methyl groups into account. The response
      factors relating that of dibenzothiophene to internal standards were obtained by
      GC-MS analyses of mixture solutions with different concentration ratios. We
      concluded that DBT-d8 (octadeutero-dibenzothiophene) is the optimal internal
      standard for quantitative analyses of the thiophene compound class in oils, coal,
      and sediment extracts. Calibration experiments for each class of compounds are
      absolutely necessary when quantifying polycyclic aromatic hydrocarbons and other
      heterocyclics with a stable isotope labeled internal standard.

PMID- 22381886
TI  - Field enhancement sample stacking for analysis of organic acids in traditional
      Chinese medicine by capillary electrophoresis.
AB  - A technique known as field enhancement sample stacking (FESS) and capillary
      electrophoresis (CE) separation has been developed to analyze and detect organic
      acids in the three traditional Chinese medicines (such as Portulaca oleracea L.,
      Crataegus pinnatifida and Aloe vera L.). In FESS, a reverse electrode polarity
      stacking mode (REPSM) was applied as on-line preconcentration strategy. Under the
      optimized condition, the baseline separation of eight organic acids (linolenic
      acid, lauric acid, p-coumaric acid, ascorbic acid, benzoic acid, caffeic acid,
      succinic acid and fumaric acid) could be achieved within 20 min. Validation
      parameters of this method (such as detection limits, linearity and precision)
      were also evaluated. The detection limits ranged from 0.4 to 60 ng/mL. The
      results indicated that the proposed method was effective for the separation of
      mixtures of organic acids. Satisfactory recoveries were also obtained in the
      analysis of these organic acids in the above traditional Chinese medicine
      samples.

PMID- 22381887
TI  - Comparative evaluation of post-column free radical scavenging and ferric reducing
      antioxidant power assays for screening of antioxidants in strawberries.
AB  - ABTS and FRAP post-column techniques evaluate the antioxidant characteristics of
      HPLC separated compounds with specific reagents. ABTS characterize their ability
      to scavenge free radicals by electron-donating antioxidants, resulting in the
      absorbance decrease of the chromophoric radical. FRAP - is based on the reduction
      of Fe(III)-tripyridyltriazine complex to Fe(II)-tripyridyltriazine at low pH by
      electron-donating antioxidants, resulting in an absorbance increase. Both post
      column assays were evaluated and compared according to the following validation
      parameters: specificity, precision, limit of detection (LoD), limit of
      quantitation (LoQ) and linearity. ABTS and FRAP post-column assays were specific,
      repeatable and sensitive and thus can be used for the evaluation of antioxidant
      active compounds. Antioxidant active compounds were quantified according to TEAC
      for each assay and ABTS/FRAP ratio was derived. No previous records of
      antioxidative activity of leaves and fruits of strawberries (Fragaria viridis,
      Fragaria moschata) research have been found. The research results confirm the
      reliability of ABTS and FRAP post-column assays for screening of antioxidants in
      complex mixtures and the determination of radical scavenging and ferric reducing
      ability by their TEAC values.

PMID- 22381888
TI  - Quantitative profiling of polar primary metabolites using hydrophilic interaction
      ultrahigh performance liquid chromatography-tandem mass spectrometry.
AB  - A hydrophilic interaction liquid chromatography (HILIC)-MS/MS profiling method
      was developed for the efficient separation and quantification of small polar
      molecules, mostly primary metabolites. The method was based on an ultrahigh
      performance liquid chromatography (UHPLC) separation system coupled with ESI mass
      spectrometry on a triple quadrupole mass spectrometer, operating in both positive
      and negative ionisation mode using rapid polarity switching. With the developed
      method quantitation of 135 compounds belonging in four major classes of polar
      compounds (sugars, aminoacids, organic acids and amines) was achieved in a single
      run of 30 min. The method was applied to grape extracts from different varieties
      and provided information on primary metabolite content. Multivariate statistical
      analysis was applied using the concentrations found, with the aim of
      investigating the differences in metabolite profiles. Classification of grapes
      according to their skin colour was carried out using principle component analysis
      based on the concentration variation of a number of the metabolites studied.

PMID- 22381889
TI  - Detection and characterization of silver nanoparticles in aqueous matrices using
      asymmetric-flow field flow fractionation with inductively coupled plasma mass
      spectrometry.
AB  - Engineered nanomaterials (EN) may be released into the environment as a result of
      their use in various consumer products. Silver nanoparticles (nAg) are widely
      used as an antimicrobial agent in personal care and household products, and in
      textiles. Since there is high potential for nAg to be released into municipal
      wastewater and then discharged into the aquatic environment, there is a need to
      develop methods for the analysis of these materials in aqueous matrices.
      Asymmetric-flow field flow fractionation (AF4) with on-line detection by ultra
      violet-visible (UV-Vis) spectroscopy or inductively coupled plasma mass
      spectrometry (ICP-MS) was used to detect and characterize nAg in aqueous
      matrices. Analysis of a mixture of 20, 40 and 60 nm nAg standards suspended in
      water resulted in a well resolved fractogram. Retention times of nAg separated by
      AF4 were correlated with the particle sizes of the standards. The limit of
      detection (LOD) for analysis of nAg using the on-line AF4/ICP-MS method was 0.80
      ng mL(-1). Two calibration approaches (i.e., external calibration and standard
      addition) were used to quantify nAg concentrations, and both methods gave similar
      results. Using the on-line AF4/ICP-MS analytical method, nano-sized Ag was
      detected and quantified in untreated wastewater (i.e., influent) collected from a
      wastewater treatment plant. The concentration and the modal size of nAg in the
      influent were 1.90 ng mL(-1) and 9.3 nm respectively.

PMID- 22381891
TI  - Operational-modes of field-flow fractionation in microfluidic channels.
AB  - Through a careful consideration of the retention ratio for field-flow
      fractionation (FFF), we show that a single unified ideal retention theory can
      predict a wide range of separation behaviours including hydrodynamic
      chromatography, normal-mode FFF and steric-mode FFF by introducing the concept of
      a device retention parameter. We determine the critical device retention
      parameter above which normal-mode does not exist and there is no clear
      distinction between hydrodynamic chromatography and steric-mode FFF. Numerical
      analysis of the elution order as a function of particle size quantitatively
      predicts the transitions between these regimes. The resulting map of the
      operational-modes shows each of the regions and their connectivity, and so may
      guide future device design. By extending this analysis to account for the
      variation of stress over particle surfaces, a hitherto unreported regime called
      Faxen-mode FFF is predicted, which has the same elution order as normal-mode FFF.
      This mode arises when particle sizes approach the channel height, as can occur
      when microfluidic devices are utilized for FFF. The transition from steric-mode
      to Faxen-mode FFF is numerically mapped and approximations for each transition
      are presented.

PMID- 22381892
TI  - Immuno-magnetic beads-based extraction-capillary zone electrophoresis-deep UV
      laser-induced fluorescence analysis of erythropoietin.
AB  - Erythropoietin (EPO) is an important glycoprotein hormone. Recombinant human EPO
      (rhEPO) is an important therapeutic drug and can be also used as doping reagent
      in sports. The analysis of EPO glycoforms in pharmaceutical and sports areas
      greatly challenges analytical scientists from several aspects, among which
      sensitive detection and effective and facile sample preparation are two essential
      issues. Herein, we investigated new possibilities for these two aspects. Deep UV
      laser-induced fluorescence detection (deep UV-LIF) was established to detect the
      intrinsic fluorescence of EPO while an immuno-magnetic beads-based extraction
      (IMBE) was developed to specifically extract EPO glycoforms. Combined with
      capillary zone electrophoresis (CZE), CZE-deep UV-LIF allows high resolution
      glycoform profiling with improved sensitivity. The detection sensitivity was
      improved by one order of magnitude as compared with UV absorbance detection. An
      additional advantage is that the original glycoform distribution can be
      completely preserved because no fluorescent labeling is needed. By combining IMBE
      with CZE-deep UV-LIF, the overall detection sensitivity was 1.5 * 10-8 mol/L,
      which was enhanced by two orders of magnitude relative to conventional CZE with
      UV absorbance detection. It is applicable to the analysis of pharmaceutical
      preparations of EPO, but the sensitivity is insufficient for the anti-doping
      analysis of EPO in blood and urine. IMBE can be straightforward and effective
      approach for sample preparation. However, antibodies with high specificity were
      the key for application to urine samples because some urinary proteins can
      severely interfere the immuno-extraction.

PMID- 22381893
TI  - Fast immobilized liposome chromatography based on penetrable silica microspheres
      for screening and analysis of permeable compounds.
AB  - In the present study, an immobilized liposome chromatography (ILC) stationary
      phase based on penetrable silica microspheres was prepared. The silica possessed
      mesopores and penetrable macropores, which afforded sufficient surface area and
      fast mass transfer, respectively. Compared with the ILC column based on common
      porous silica gels, the penetrable silica had larger capacity for liposomes'
      immobilization, lower backpressure and higher separation efficiency. Twenty-two
      kinds of drugs were used as tested analytes and their retention behaviors on
      newly prepared ILC column were investigated in detail. Column temperature and pH
      of mobile phase were both key factors affecting the retention of solutes. The
      retention of these drugs on ILC column reflected their permeability in vivo.
      Furthermore, the methanolic aqueous extracts of three traditional Chinese
      medicines (TCMs), Radix Liquiritiae, Scutellaria Baicalensis and Flos Sophorae,
      were screened on this novel ILC column. Effects of column temperature and eluent
      pH on chromatographic behaviors of components of the TCM methanolic extracts were
      also studied. Several permeable components can be found, indicating that they are
      potentially active components in the TCMs. It is also found that the as-prepared
      ILC column remained stable in at least 1 month and the relative standard
      deviations of adjusted retention times for solutes were lower than 9.0%. The
      proposed ILC based on the penetrable silica microspheres is promising for the
      fast and low-pressure separation, especially for fast screening of permeable
      compounds and modeling the drug-membrane interaction in vitro. It would be a
      useful approach to predict the permeability of potential active drugs.

PMID- 22381894
TI  - Bradykinin-induced leukocyte- and platelet-endothelium interactions in the
      cerebral microcirculation.
AB  - Bradykinin is known for its pathophysiological role as mediator of inflammation.
      Following cerebral ischemia, bradykinin promotes the secondary brain damage
      through an increase of vascular permeability and brain edema formation, again
      hallmarks of inflammation. It is not clear, whether bradykinin also activates
      inflammatory cells and regulates microcirculatory blood flow in the brain. The
      purpose of the study is to investigate the reaction of bradykinin upon cerebral
      leukocyte- and thrombocyte-endothelium interactions as well as microvascular
      perfusion. Intravital fluorescence microscopy of pial blood vessels was performed
      in gerbils. Intracarotid injection of bradykinin resulted in increased numbers of
      rolling and adherent leukocytes as well as rolling platelets at the venular
      endothelium. This was reversed by administration of a bradykinin B2 receptor
      antagonist. In contrast, after additional administration of a B1 receptor
      antagonist, microvascular blood-flow and capillary density was decreased. We
      conclude that bradykinin initiates leukocyte- and platelet-endothelium
      interactions in the cerebral microcirculation via activation of B2 receptors.
      Activation of B1 receptors ensures regular cerebral perfusion. Thus, to attenuate
      secondary brain damage, inhibition of B2 but not B1 receptors might be of
      therapeutical benefit.

PMID- 22381895
TI  - Regulatory mechanism of body temperature in the central nervous system during the
      maintenance phase of hibernation in Syrian hamsters: involvement of beta
      endorphin.
AB  - We have shown previously that intracerebroventricular (icv) injection of naloxone
      (a non-selective opioid receptor antagonist) or naloxonazine (a selective MU1
      opioid receptor antagonist) at the maintenance phase of hibernation arouses
      Syrian hamsters from hibernation. This study was designed to clarify the role of
      beta-endorphin (an endogenous MU-opioid receptor ligand) on regulation of body
      temperature (T(b)) during the maintenance phase of hibernation. The number of c
      Fos-positive cells and beta-endorphin-like immunoreactivity increased in the
      arcuate nucleus (ARC) after hibernation onset. In contrast, endomorphin-1 (an
      endogenous MU-opioid receptor ligand)-like immunoreactivity observed on the
      anterior hypothalamus decreased after hibernation onset. In addition, hibernation
      was interrupted by icv injection of anti-beta-endorphin antiserum at the
      maintenance phase of hibernation. The mRNA expression level of
      proopiomelanocortin (a precursor of beta-endorphin) on ARC did not change
      throughout the hibernation phase. However, the mRNA expression level of
      prohormone convertase-1 increased after hibernation onset. [D-Ala2,N-MePhe4,Gly
      ol5] enkephalin (DAMGO, a selective MU-opioid receptor agonist) microinjection
      into the dorsomedial hypothalamus (DMH) elicited the most marked T(b) decrease
      than other sites such as the preoptic area (PO), anterior hypothalamus (AH),
      lateral hypothalamus (LH), ventromedial hypothalamus and posterior hypothalamus
      (PH). However, microinjected DAMGO into the medial septum indicated negligible
      changes in T(b). These results suggest that beta-endorphin which synthesizes in
      ARC neurons regulates T(b) during the maintenance phase of hibernation by
      activating MU-opioid receptors in PO, AH, VMH, DMH and PH.

PMID- 22381896
TI  - Micro-scale investigation of intestinal schistosomiasis transmission on Ngamba
      and Kimi islands, Lake Victoria, Uganda.
AB  - A study to investigate the effect of environmental predictors on abundance of
      Biomphalaria, the intermediate host snails of Schistosoma mansoni, was carried
      out on two small islands in Lake Victoria, Uganda. Malacological surveys were
      performed at 40 shoreline sites on Kimi and Ngamba islands documenting occurrence
      of Biomphalaria; other environmental and limnological conditions were also
      recorded, including gastropod community diversity. Snails were examined for
      shedding of schistosomes and emerging cercariae were DNA 'barcoded'. For
      population genetics analysis of Biomphalaria, snails from four populations from
      each island were also sequenced. Aquatic phosphate concentrations were higher on
      Kimi island, confirming greater anthropogenic influence, although, snail species
      diversity and community assemblages were not significantly different between
      islands. Bayesian geostatistical models were fitted to assess the effect of
      environmental factors on Biomphalaria abundance and snails' risk of shedding
      schistosome or non-schistosome cercariae. No factors were found to be significant
      in the spatial model. The local population genetics of S. mansoni and
      Biomphalaria on each island followed similar patterns as that seen in previous
      studies on a lake-wide basis. These findings suggest that smaller scale studies
      may prove useful as proxies for regional level investigations, with reduced
      logistical and resource output required. However, further research should also
      include surveys of terminal host parasite burden, as these will affect even micro
      scale dynamics of parasite-intermediate host interactions, as well as be
      important from a public health perspective in their own right. 

PMID- 22381897
TI  - Radiosensitizing effect of a phenylbutyrate-derived histone deacetylase inhibitor
      in hepatocellular carcinoma.
AB  - PURPOSE: Radiotherapy is integrated into the multimodal treatment of localized
      hepatocellular carcinoma (HCC) refractory to conventional treatment. Tumor
      control remains unsatisfactory and the sublethal effect associates with secondary
      spread. The use of an effective molecularly targeted agent in combination with
      radiotherapy is a potential therapeutic approach. Our aim was to assess the
      effect of combining a phenylbutyrate-derived histone deacetylase (HDAC)
      inhibitor, AR-42, with radiotherapy in in vitro and in vivo models of human HCC.
      METHODS AND MATERIALS: Human HCC cell lines (Huh-7 and PLC-5) were used to
      evaluate the in vitro synergism of combining AR-42 with irradiation. Flow
      cytometry analyzed the cell cycle changes, whereas Western blot investigated the
      protein expressions after the combined treatment. Severe combined immunodeficient
      (SCID) mice bearing ectopic and orthotopic HCC xenografts were treated with AR-42
      and/or radiotherapy for the in vivo response. RESULTS: AR-42 significantly
      enhanced radiation-induced cell death by the inhibition of the DNA end-binding
      activity of Ku70, a highly versatile regulatory protein for DNA repair, telomere
      maintenance, and apoptosis. In ectopic xenografts of Huh-7 and PLC-5,
      pretreatment with AR-42 significantly enhanced the tumor-suppressive effect of
      radiotherapy by 48% and 66%, respectively. A similar combinatorial effect of AR
      42 (10 and 25 mg/kg) and radiotherapy was observed in Huh-7 orthotopic model of
      tumor growth by 52% and 82%, respectively. This tumor suppression was associated
      with inhibition of intratumoral Ku70 activity as well as reductions in markers of
      HDAC activity and proliferation, and increased apoptosis. CONCLUSION: AR-42 is a
      potent, orally bioavailable inhibitor of HDAC with therapeutic value as a
      radiosensitizer of HCC.

PMID- 22381898
TI  - Analysis of dosimetric parameters associated with acute gastrointestinal toxicity
      and upper gastrointestinal bleeding in locally advanced pancreatic cancer
      patients treated with gemcitabine-based concurrent chemoradiotherapy.
AB  - PURPOSE: To identify the dosimetric parameters associated with gastrointestinal
      (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated
      with gemcitabine-based chemoradiotherapy. METHODS AND MATERIALS: The data from 40
      patients were analyzed retrospectively. Chemoradiotherapy consisted of
      conventional fractionated three-dimensional radiotherapy and weekly gemcitabine.
      Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded
      according to the Common Toxicity Criteria Adverse Events, version 4.0. The
      dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm(3) of
      the organ, and absolute volume receiving 10-50 Gy [V(10-50)]) of the stomach,
      duodenum, small intestine, and a composite structure of the stomach and duodenum
      (StoDuo) were obtained. The planning target volume was also obtained. Univariate
      analyses were performed to identify the predictive factors for the risk of grade
      2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. RESULTS:
      The median follow-up period was 15.7 months (range, 4-37). The actual incidence
      of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%.
      Regarding acute GI toxicity, a V(50) of >= 16 cm(3) of the stomach was the best
      predictor, and the actual incidence in patients with V(50) <16 cm(3) of the
      stomach vs. those with V(50) of >= 16 cm(3) was 9% vs. 61%, respectively (p =
      0.001). Regarding UGB, V(50) of >= 33 cm(3) of the StoDuo was the best predictor,
      and the estimated incidence at 1 year in patients with V(50) <33 cm(3) of the
      StoDuo vs. those with V(50) >= 33 cm(3) was 0% vs. 44%, respectively (p = 0.002).
      The dosimetric parameters correlated highly with one another. CONCLUSION: The
      irradiated absolute volume of the stomach and duodenum are important for the risk
      of acute GI toxicity and UGB. These results could be helpful in escalating the
      radiation doses using novel techniques, such as intensity-modulated radiotherapy,
      for the treatment of pancreatic cancer.

PMID- 22381899
TI  - Prospective preference assessment of patients' willingness to participate in a
      randomized controlled trial of intensity-modulated radiotherapy versus proton
      therapy for localized prostate cancer.
AB  - PURPOSE: To investigate patients' willingness to participate (WTP) in a
      randomized controlled trial (RCT) comparing intensity-modulated radiotherapy
      (IMRT) with proton beam therapy (PBT) for prostate cancer (PCa). METHODS AND
      MATERIALS: We undertook a qualitative research study in which we prospectively
      enrolled patients with clinically localized PCa. We used purposive sampling to
      ensure a diverse sample based on age, race, travel distance, and physician.
      Patients participated in a semi-structured interview in which they reviewed a
      description of a hypothetical RCT, were asked open-ended and focused follow-up
      questions regarding their motivations for and concerns about enrollment, and
      completed a questionnaire assessing characteristics such as demographics and
      prior knowledge of IMRT or PBT. Patients' stated WTP was assessed using a 6-point
      Likert scale. RESULTS: Forty-six eligible patients (33 white, 13 black) were
      enrolled from the practices of eight physicians. We identified 21 factors that
      impacted patients' WTP, which largely centered on five major themes:
      altruism/desire to compare treatments, randomization, deference to physician
      opinion, financial incentives, and time demands/scheduling. Most patients (27 of
      46, 59%) stated they would either "definitely" or "probably" participate.
      Seventeen percent (8 of 46) stated they would "definitely not" or "probably not"
      enroll, most of whom (6 of 8) preferred PBT before their physician visit.
      CONCLUSIONS: A substantial proportion of patients indicated high WTP in a RCT
      comparing IMRT and PBT for PCa.

PMID- 22381900
TI  - Inhibiting the aurora B kinase potently suppresses repopulation during
      fractionated irradiation of human lung cancer cell lines.
AB  - PURPOSE: The use of molecular-targeted agents during radiotherapy of non-small
      cell lung cancer (NSCLC) is a promising strategy to inhibit repopulation, thereby
      improving therapeutic outcome. We assessed the combined effectiveness of
      inhibiting Aurora B kinase and irradiation on human NSCLC cell lines in vitro.
      METHODS AND MATERIALS: NSCLC cell lines were exposed to concentrations of AZD1152
      hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) inhibiting colony formation by
      50% (IC50(clone)) in combination with single dose irradiation or different
      fractionation schedules using multiple 2-Gy fractions per day up to total doses
      of 4-40 Gy. The total irradiation dose required to control growth of 50% of the
      plaque monolayers (TCD50) was determined. Apoptosis, G2/M progression, and
      polyploidization were also analyzed. RESULTS: TCD50 values after single dose
      irradiation were similar for the H460 and H661 cell lines with 11.4 +/- 0.2 Gy
      and 10.7 +/- 0.3 Gy, respectively. Fractionated irradiation using 3 * 2 Gy/day, 2
      * 2 Gy/day, and 1 * 2 Gy/day schedules significantly increased TCD50 values for
      both cell lines grown as plaque monolayers with increasing radiation treatment
      time. This could be explained by a repopulation effect per day that counteracts
      75 +/- 8% and 27 +/- 6% of the effect of a 2-Gy fraction in H460 and H661 cells,
      respectively. AZD1152-HQPA treatment concomitant to radiotherapy significantly
      decreased the daily repopulation effect (H460: 28 +/- 5%, H661: 10 +/- 4% of a 2
      Gy fraction per day). Treatment with IC50(clone) AZD1152-HPQA did not induce
      apoptosis, prolong radiation-induced G2 arrest, or delay cell cycle progression
      before the spindle check point. However, polyploidization was detected,
      especially in cell lines without functional p53. CONCLUSIONS: Inhibition of
      Aurora B kinase with low AZD1152-HQPA concentrations during irradiation of NSCLC
      cell lines affects repopulation during radiotherapy. Thus, concomitant Aurora B
      kinase inhibition and irradiation may be a promising strategy for fast
      repopulating tumors, which are difficult to cure by dose escalation based on
      conventional fractionation.

PMID- 22381901
TI  - Dynamic contrast-enhanced magnetic resonance imaging of the metastatic potential
      of melanoma xenografts.
AB  - PURPOSE: Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested as a
      useful noninvasive method for characterizing the physiologic microenvironment of
      tumors. In the present study, we investigated whether Gd-DTPA-based DCE-MRI has
      the potential to provide biomarkers for hypoxia-associated metastatic
      dissemination. METHODS AND MATERIALS: C-10 and D-12 melanoma xenografts were used
      as experimental tumor models. Pimonidazole was used as a hypoxia marker. A total
      of 60 tumors were imaged, and parametric images of K(trans) (volume transfer
      constant of Gd-DTPA) and v(e) (fractional distribution volume of Gd-DTPA) were
      produced by pharmacokinetic analysis of the DCE-MRI series. The host mice were
      killed immediately after DCE-MRI, and the primary tumor and the lungs were
      resected and prepared for histologic assessment of the fraction of pimonidazole
      positive hypoxic tissue and the presence of lung metastases, respectively.
      RESULTS: Metastases were found in 11 of 26 mice with C-10 tumors and 14 of 34
      mice with D-12 tumors. The primary tumors of the metastatic-positive mice had a
      greater fraction of hypoxic tissue (p = 0.00031, C-10; p < 0.00001, D-12), a
      lower median K(trans) (p = 0.0011, C-10; p < 0.00001, D-12), and a lower median
      v(e) (p = 0.014, C-10; p = 0.016, D-12) than the primary tumors of the metastatic
      negative mice. CONCLUSIONS: These findings support the clinical attempts to
      establish DCE-MRI as a method for providing biomarkers for tumor aggressiveness
      and suggests that primary tumors characterized by low K(trans) and low v(e)
      values could have a high probability of hypoxia-associated metastatic spread.

PMID- 22381902
TI  - Patterns of practice in palliative radiotherapy for painful bone metastases: a
      survey in Japan.
AB  - PURPOSE: To determine the current patterns of practice in Japan and to
      investigate factors that may make clinicians reluctant to use single-fraction
      radiotherapy (SF-RT). METHODS AND MATERIALS: Members of the Japanese Radiation
      Oncology Study Group (JROSG) completed an Internet-based survey and described the
      radiotherapy dose fractionation they would recommend for four hypothetical cases
      describing patients with painful bone metastasis (BM). Case 1 described a patient
      with an uncomplicated painful BM in a non-weight-bearing site from non-small-cell
      lung cancer. Case 2 investigated whether management for a case of uncomplicated
      spinal BM would be different from that in Case 1. Case 3 was identical with Case
      2 except for the presence of neuropathic pain. Case 4 investigated the
      prescription for an uncomplicated painful BM secondary to oligometastatic breast
      cancer. Radiation oncologists who recommended multifraction radiotherapy (MF-RT)
      for Case 2 were asked to explain why they considered MF-RT superior to SF-RT.
      RESULTS: A total of 52 radiation oncologists from 50 institutions (36% of JROSG
      institutions) responded. In all four cases, the most commonly prescribed regimen
      was 30 Gy in 10 fractions. SF-RT was recommended by 13% of respondents for Case
      1, 6% for Case 2, 0% for Case 3, and 2% for Case 4. For Case 4, 29% of
      respondents prescribed a high-dose MF-RT regimen (e.g., 50 Gy in 25 fractions).
      The following factors were most often cited as reasons for preferring MF-RT:
      "time until first increase in pain" (85%), "incidence of spinal cord compression"
      (50%), and "incidence of pathologic fractures" (29%). CONCLUSIONS: Japanese
      radiation oncologists prefer a schedule of 30 Gy in 10 fractions and are less
      likely to recommend SF-RT. Most Japanese radiation oncologists regard MF-RT as
      superior to SF-RT, based primarily on the time until first increase in pain.

PMID- 22381903
TI  - Influence of tumor thrombus location on the outcome of external-beam radiation
      therapy in advanced hepatocellular carcinoma with macrovascular invasion.
AB  - PURPOSE: The present study evaluates the influence of portal vein (PV) vs.
      inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external
      beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with
      macrovascular invasion. METHODS AND MATERIALS: We retrospectively reviewed 181
      HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our
      institution between 2000 and 2009. EBRT was designed to focus on the tumor
      thrombi with or without primary intrahepatic tumors to deliver a median total
      conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were
      identified using univariate and multivariate analyses. RESULTS: The median
      survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV
      trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable
      pretreatment predictors were associated by multivariate analysis with lower
      albumin and higher alpha-fetoprotein levels, poorer Child-Pugh liver function
      classification, multiple intrahepatic foci, lymph node metastases, thrombus
      location, less chance to receive post-EBRT transarterial chemoembolization (TACE)
      and the two-dimensional EBRT technique. In comparison to patients with PV tumor
      thrombosis, patients with IVC thrombi had a higher occurrence of solitary
      intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p <
      0.001), and a better response to EBRT (p < 0.001), and they were more likely to
      receive post-EBRT TACE (p = 0.033). CONCLUSIONS: In HCC, patients with IVC
      thrombus treated with EBRT had a better response rate and longer survival than
      those with PV thrombus.

PMID- 22381904
TI  - Postchemoradiotherapy positron emission tomography predicts pathologic response
      and survival in patients with esophageal cancer.
AB  - PURPOSE: To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor
      volume (MTV) on positron emission tomography (PET) scanning with the pathologic
      response and survival in patients receiving preoperative CRT for esophageal
      cancer. MATERIALS AND METHODS: The medical records of 37 patients with
      histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or
      without surgical resection were reviewed. Of the 37 patients, 21 received
      preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a
      pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET
      and post-CRT PET scan, respectively, using a minimum standardized uptake value
      (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum * 50%. The total
      glycolytic activity (TGA(x)) was defined as the mean SUV * MTV(x). The MTV ratio
      was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined
      similarly. A single pathologist scored the pathologic response using a tumor
      regression grade (TRG) scale. RESULTS: The median follow-up was 1.5 years (range,
      0.4-4.9). No significant correlation was found between any parameters on the pre
      CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values
      and post-TGA values correlated with the TRG and OS; however, the MTV(2.5(Post))
      and TGA(2.5(Post)) had the greatest correlation. The MTV(2) ratio correlated with
      OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum
      SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively
      had survival similar compared with those treated definitively with a good PET
      response (p = 0.97) and significantly better than that of patients treated
      definitively with a poor PET response (p < 0.0001). CONCLUSION: The maximum SUV
      was not a predictive or prognostic parameter. The MTV(2.5) and TGA(2.5) were
      useful markers for predicting the response and survival on the post-CRT PET scan.
      The MTV(2) ratio also correlated with survival. Post-CRT PET can potentially
      guide therapy after CRT.

PMID- 22381905
TI  - Inter- and intrafraction uncertainty in prostate bed image-guided radiotherapy.
AB  - PURPOSE: The goals of this study were to measure inter- and intrafraction setup
      error and prostate bed motion (PBM) in patients undergoing post-prostatectomy
      image-guided radiotherapy (IGRT) and to propose appropriate population-based
      three-dimensional clinical target volume to planning target volume (CTV-PTV)
      margins in both non-IGRT and IGRT scenarios. METHODS AND MATERIALS: In this
      prospective study, 14 patients underwent adjuvant or salvage radiotherapy to the
      prostate bed under image guidance using linac-based kilovoltage cone-beam CT (kV
      CBCT). Inter- and intrafraction uncertainty/motion was assessed by offline
      analysis of three consecutive daily kV-CBCT images of each patient: (1) after
      initial setup to skin marks, (2) after correction for positional
      error/immediately before radiation treatment, and (3) immediately after
      treatment. RESULTS: The magnitude of interfraction PBM was 2.1 mm, and
      intrafraction PBM was 0.4 mm. The maximum inter- and intrafraction prostate bed
      motion was primarily in the anterior-posterior direction. Margins of at least 3-5
      mm with IGRT and 4-7 mm without IGRT (aligning to skin marks) will ensure 95% of
      the prescribed dose to the clinical target volume in 90% of patients.
      CONCLUSIONS: PBM is a predominant source of intrafraction error compared with
      setup error and has implications for appropriate PTV margins. Based on inter- and
      estimated intrafraction motion of the prostate bed using pre- and post-kV-CBCT
      images, CBCT IGRT to correct for day-to-day variances can potentially reduce CTV
      PTV margins by 1-2 mm. CTV-PTV margins for prostate bed treatment in the IGRT and
      non-IGRT scenarios are proposed; however, in cases with more uncertainty of
      target delineation and image guidance accuracy, larger margins are recommended.

PMID- 22381906
TI  - Exposure to ionizing radiation causes long-term increase in serum estradiol and
      activation of PI3K-Akt signaling pathway in mouse mammary gland.
AB  - PURPOSE: Exposure to ionizing radiation is an established risk factor for breast
      cancer. Radiation exposure during infancy, childhood, and adolescence confers the
      highest risk. Although radiation is a proven mammary carcinogen, it remains
      unclear where it acts in the complex multistage process of breast cancer
      development. In this study, we investigated the long-term pathophysiologic
      effects of ionizing radiation at a dose (2 Gy) relevant to fractionated
      radiotherapy. METHODS AND MATERIALS: Adolescent (6-8 weeks old; n = 10) female
      C57BL/6J mice were exposed to 2 Gy total body gamma-radiation, the mammary glands
      were surgically removed, and serum and urine samples were collected 2 and 12
      months after exposure. Molecular pathways involving estrogen receptor-alpha
      (ERalpha) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were
      investigated by immunohistochemistry and Western blot. RESULTS: Serum estrogen
      and urinary levels of the oncogenic estrogen metabolite (16alphaOHE1) were
      significantly increased in irradiated animals. Immunostaining for the cellular
      proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in
      sections of mammary glands from irradiated vs. control mice. Marked increase in
      p85alpha, a regulatory sub-unit of the PI3K was associated with increase in Akt,
      phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples.
      Persistent increase in nuclear ERalpha in mammary tissues 2 and 12 months after
      radiation exposure was also observed. CONCLUSIONS: Taken together, our data not
      only support epidemiologic observations associating radiation and breast cancer
      but also, specify molecular events that could be involved in radiation-induced
      breast cancer.

PMID- 22381907
TI  - Tumor volume-adapted dosing in stereotactic ablative radiotherapy of lung tumors.
AB  - PURPOSE: Current stereotactic ablative radiotherapy (SABR) protocols for lung
      tumors prescribe a uniform dose regimen irrespective of tumor size. We report the
      outcomes of a lung tumor volume-adapted SABR dosing strategy. METHODS AND
      MATERIALS: We retrospectively reviewed the outcomes in 111 patients with a total
      of 138 primary or metastatic lung tumors treated by SABR, including local
      control, regional control, distant metastasis, overall survival, and treatment
      toxicity. We also performed subset analysis on 83 patients with 97 tumors treated
      with a volume-adapted dosing strategy in which small tumors (gross tumor volume
      <12 mL) received single-fraction regimens with biologically effective doses (BED)
      <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume
      >=12 mL) received multifraction regimens with BED >=100 Gy (total dose, 50-60 Gy
      in three to four fractions) (Group 2). RESULTS: The median follow-up time was
      13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively
      (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases),
      local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control,
      freedom from distant metastasis, and overall survival did not differ
      significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall
      toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities
      developed in Group 2 (p = 0.02). CONCLUSION: A volume-adapted dosing approach for
      SABR of lung tumors seems to provide excellent local control for both small- and
      large-volume tumors and may reduce toxicity.

PMID- 22381908
TI  - Emerging diabetes therapies and technologies.
AB  - The prevalence of diabetes is increasing globally and is expected to increase to
      439 million people by the year 2030. Several studies have shown that improved
      glycemic control measured by glycosylated hemoglobin (A1c) in patients with type
      1 and type 2 diabetes results in a reduction of both the micro- and macrovascular
      complications associated with the disease. The recent introduction of new oral
      medications, insulin analogs (long and rapid acting), insulin pens and pumps,
      better SMBG meters and continuous glucose monitoring (CGM) have all resulted in
      improvement of glycemic control. Closed-loop devices currently in development aim
      to integrate the CGM and pump system in order to more closely mimic the human
      pancreas. The other upcoming new basal insulin (Degludec), prandial insulin,
      other new technologies and improved oral therapies will significantly improve
      patient acceptance of intensive therapy, glycemic control and quality of life in
      patients with diabetes.

PMID- 22381909
TI  - Hypereosinophilic syndrome with cardiac involvement: early diagnosis by cardiac
      magnetic resonance imaging.
AB  - Cardiac manifestation is the major cause of morbidity in patients with
      hypereosinophilic syndrome (HES) if left untreated. Endomyocardial biopsy is
      currently the gold standard for diagnosis, although typical findings using
      noninvasive methods such as cardiac magnetic resonance (CMR), may suggest the
      diagnosis. The present case provides an example of the beneficial use of cardiac
      magnetic resonance for early diagnosis and follow-up of patients with cardiac
      involvement in hypereosinophilic syndrome.

PMID- 22381910
TI  - Infective endocarditis presenting as ST-elevation myocardial infarction: an
      angiographic diagnosis.
AB  - While systemic embolic events occur with relative frequency in infective
      endocarditis (IE), coronary embolization remains an uncommon cause of ST
      elevation myocardial infarction. Herein we report a case of ventricular
      fibrillation and anterior ST elevation myocardial infarction occurring in a
      patient initially presenting with septic shock. Angiography proved diagnostic for
      IE of a native bicuspid aortic valve complicated by root abscess and left
      anterior descending artery occlusion. Histologic examination of the embolectomy
      specimen from the left anterior descending artery confirmed the presence of
      thrombus and bacteria. The present case highlights difficulties in identifying
      and managing patients with coronary embolism of vegetations from IE.

PMID- 22381911
TI  - PalI domain proteins of Saccharomyces cerevisiae and Candida albicans.
AB  - The Rim9/PalI groups of proteins are members of the Sur7 family, all of which
      contain a signal sequence and a block of three potential trans-membrane helices.
      Multi-protein sequence comparisons among fungi suggest that there are two classes
      of Rim9/PalI proteins; longer proteins like PalI that contain a Sur7 domain and a
      C-terminal extension, and shorter proteins like Rim9 that contain essentially
      only the Sur7 domain. We have examined possible roles of the longer, PalI-like
      proteins of both Saccharomyces cerevisiae (Yol019w) and Candida albicans
      (Orf19.1510/Srd1), two species that also contain short Rim9 proteins required for
      alkaline-associated stress responses. Deletions of the long form genes did not
      create any significant stress response phenotype in either S. cerevisiae or C.
      albicans, nor did the deletions enhance any of the rim9 deletion effects when
      combined in a double mutant. Furthermore, challenges in C. albicans show RIM9 but
      not SRD1 is important for proper response and hyphal formation. It appears that
      in fungal species such as Aspergillus nidulans containing only a long-form PalI
      like protein, this element functions in the process of stress response, while in
      fungi with both versions the response to stress function is limited to the short
      form protein.

PMID- 22381912
TI  - Tasmancin and lysogenic bacteriophages induced from Erwinia tasmaniensis strains.
AB  - Mitomycin C treatment of Erwinia tasmaniensis strains from Australia induced
      prophages and the expression of bacteriocins. The bacteriocin named tasmancin
      inhibited E. tasmaniensis strains from South Africa and Germany. A gene cluster
      with a klebicin-related operon and an immunity protein was detected on plasmid
      pET46 from E. tasmaniensis strain Et1/99. PCR reactions using primers directed to
      this region produced signals for several strains originating from Australia, but
      not for strains isolated in South Africa and Germany. The latter isolates lacked
      plasmid pET46. Bacteriophages were induced from E. tasmaniensis strains Et88 and
      Et14/99, both isolates from South-Eastern Australia. These phages formed plaques
      on several other strains from this region, as well as on E. tasmaniensis strains
      from South Africa and Germany. Sequencing revealed similarity of phages phiEt88
      and phiEt14, which shared the host range on E. tasmaniensis strains.
      Bacteriophages and tasmancin may interfere with the viability of several related
      E. tasmaniensis strains in the environment of carrier strains.

PMID- 22381913
TI  - X-ray absorption spectroscopy of metal site speciation in the metallo-beta
      lactamase BcII from Bacillus cereus.
AB  - Cobalt and zinc binding by the subclass B1 metallo-beta-lactamase BcII from
      Bacillus cereus is examined by X-ray absorption spectroscopy, at various levels
      of metal loading. The data show that a significant amount of the dinuclear enzyme
      is formed, even at substoichiometric levels of metal loading, whether the added
      metal is Zn(II) or Co(II). Increasing metal addition, from 0.5 to 1.0 to
      2.0eq/mol of enzyme, are shown to result in a more ordered active site. While
      Zn(II) appears to show no preference for the Zn(1) (3H) or Zn(2) (DCH) sites, the
      extended X-ray absorption fine structure (EXAFS) suggests that Co(II) shows a
      slight preference for the DCH site at low levels of added Co(II). The results are
      discussed in the context of similar metal-binding studies of other B1 metallo
      beta-lactamases.

PMID- 22381914
TI  - Dealing with aggressive methadone patients in community pharmacy: a critical
      incident study.
AB  - BACKGROUND: Community pharmacists are an important link between methadone
      patients and the health service in the United Kingdom. However, many pharmacists
      feel ill prepared to deal with methadone patients, with aggressive behavior a
      particular concern. OBJECTIVE: To assess the perceived impact of methadone
      patient aggression on pharmacy practice. METHODS: Sixteen registered pharmacists
      with a minimum of 3 years' work experience were recruited from within 3 Scottish
      health boards. Critical incident interviews were conducted to assess pharmacist
      behavior during an interaction with an aggressive methadone patient. RESULTS:
      Factors considered by pharmacists to have a negative impact on an interaction
      with an aggressive methadone patient included intoxication of the patient, the
      presence of a new or an inexperienced pharmacist, and a restricted time frame for
      dispensing methadone. Positive factors when dealing with aggressive patients were
      authoritative behavior by the pharmacist, a separate dispensing area for
      methadone patients, or a solid counter and a positive relationship between
      pharmacist and patient. CONCLUSION: Aggression from methadone patients is a risk
      when dispensing methadone. However, action can be taken by the pharmacist to
      minimize the impact of that aggression on pharmacy practice. The provision of
      further training and support, particularly to inexperienced pharmacists, could
      further reduce the negative impact of patient aggression. The present study
      indicates that such training could be based on nontechnical skills to strengthen
      current leadership and teamwork behaviors.

PMID- 22381915
TI  - Information sources used by parents to learn about medications they are giving
      their children.
AB  - BACKGROUND: Previous studies have indicated the use of medication by children to
      be dependent on the attitudes of knowledge of their parents; however, little is
      known about sources parents might use in driving medication use decisions.
      OBJECTIVE: The aim of this study was to describe the information sources that
      parents use regarding their children's medication and their perceptions of the
      reliability of these information sources. METHODS: This study is part of a cross
      sectional population survey with a random sample of 6000 children younger than 12
      years. The response rate of the questionnaire was 67%. Parents were asked about
      the use of information sources and their perception of reliability with a list of
      16 information sources. RESULTS: The information sources that parents reported
      having used were physicians (72%), patient information leaflets (PILs) (67%),
      public or school health nurses (52%), and pharmacists (44%). Regardless of the
      child's age, physicians were the parents' most-used information source.
      Physicians were the most-used information source also when the child had at least
      1 of the 4 most common long-term diseases among children in Finland (asthma,
      diabetes, epilepsy, and juvenile idiopathic arthritis). Parents considered
      physicians (50%), PILs (31%), pharmacists (27%), nurses (20%), and public or
      school health nurses (17%) very reliable information sources. CONCLUSIONS:
      Finnish parents seek information from health care professionals and PILs when
      looking for information concerning their children's medication. Furthermore, they
      find health care professionals and PILs to be reliable information sources.

PMID- 22381916
TI  - Patients' willingness to use a pharmacist-provided medication management service:
      the influence of outcome expectancies and communication efficacy.
AB  - BACKGROUND: Previous research has demonstrated that some patients who are at risk
      of experiencing medication-related problems express a lack of willingness to use
      pharmacist-provided medication management services. Little is known about the
      factors that influence willingness to use these services among patients who have
      not yet experienced the service. OBJECTIVES: The aim of this study was to test a
      model of willingness to use the Australian Home Medicines Review (HMR) service.
      Specifically, this study aimed to determine the influence of positive and
      negative outcome expectancies and communication efficacy over willingness among
      patients who were eligible to receive the service but have not yet experienced
      it. METHODS: A cross-sectional survey was conducted with patients who were
      recruited by 264 community pharmacists throughout Australia. Patients were
      included in the study if they had not yet experienced HMR but were taking more
      than 5 medicines daily or more than 12 doses daily. Measurement scales were
      developed using exploratory and confirmatory factor analyses. Structural equation
      modeling was used to test the model. RESULTS: Questionnaires received from 286
      patients (15.6%) were analyzed. Multi-item measurement scales were observed to
      have acceptable construct reliabilities (range, 0.69-0.94). Importantly,
      respondents held overall neutral expectations about the personal benefits of HMR
      (positive outcome expectancies) but high communication efficacy. Structural
      equation modeling revealed that positive outcome expectancies (beta=0.56, P<.001)
      and communication efficacy (beta=0.25, P<.05) influenced willingness to use,
      whereas negative outcome expectancies had no significant effect. CONCLUSIONS: The
      extent to which patients believe that HMR would provide them with increased
      medicines knowledge, improve their medicines management capability, and reduce
      their medicine concerns had a significant influence over willingness to use the
      service. Because these expectancies are relatively low, there appears to be
      significant scope for increasing patient demand for these services. Patient
      directed material about medication management services should highlight the
      provision of medication information.

PMID- 22381917
TI  - The clinical significance of autoantibodies to the proliferating cell nuclear
      antigen (PCNA).
AB  - Autoantibodies targeting the proliferating cell nuclear antigen (PCNA) were first
      described over 30 years ago and are historically most commonly associated with
      systemic lupus erythematosus (SLE). The primary antigenic target is a 34 kDa
      protein that is part of the DNA polymerase delta multi-protein complex. A number
      of diagnostic platforms have incorporated PCNA into their diagnostic assays and
      algorithms. However, little is known about the clinical utility of autoantibodies
      to PCNA, especially with novel detection systems. This review will focus on the
      history of the discovery of the PCNA autoantigen and the current status of the
      diagnostic significance of anti-PCNA and suggest future studies that are required
      to strengthen our understanding of their clinical utility.

PMID- 22381918
TI  - Multiple ganciclovir-resistant strains in a newborn with symptomatic congenital
      human cytomegalovirus infection.
AB  - A case of human cytomegalovirus (HCMV) drug-resistance in a congenitally infected
      newborn is described. Unusual aspects of this case include: (i) the detection of
      an extremely complex virus population, composed of a mixture of wild-type (wt)
      and multiple mutant ganciclovir (GCV) and valganciclovir (val-GCV) resistant
      strains carrying a variety of known mutations in UL97; (ii) the identification of
      novel UL97 mutations and (iii) the first time detection of combined UL97 drug
      resistance mutations in the same viral strain. In detail, four known UL97 single
      nucleotide mutations (A594T/V, M460V/I, C592G), a new amino-acid substitution
      (C607S), and a new deletion (597-600) in one of the three UL97 hot spots for
      GCV/val-GCV resistance (codons 460, 520 and 590-607) were detected. In addition,
      the combination of M460V+A594V and M460V+C592G was observed for the first time.
      The emergence of HCMV drug-resistance in symptomatic congenital infections
      chronically treated with GCV or val-GCV should be taken into account. The
      immaturity of the neonatal immune system may contribute to selection of complex
      virus populations in these patients.

PMID- 22381919
TI  - Rapid HIV screening: missed opportunities for HIV diagnosis and prevention.
AB  - BACKGROUND: Although rapid HIV tests increase the number of persons who are aware
      of their HIV status, they may fail to detect early HIV infection. OBJECTIVES: To
      evaluate the sensitivity for early HIV infection of several rapid tests and third
      and fourth-generation assays compared with nucleic acid amplification testing
      (NAAT). STUDY DESIGN: Sensitivity for early HIV infection was evaluated using 62
      NAAT-positive/WB-negative or indeterminate specimens from the CDC Acute HIV
      Infection study. Specimens underwent third-generation testing with Genetic
      Systems 1/2+O((r)) and rapid testing with Multispot HIV-1/HIV-2. A subset was
      also tested with four FDA-approved rapid tests and Determine HIV-1
      Antigen/Antibody Rapid Test((r)) and Architect HIV Antigen/Antibody Combo((r)),
      both fourth-generation tests. RESULTS: Of 99,111 specimens screened from April
      2006 to March 2008, 62 met the definition for early HIV infection (60 NAAT
      positive/seronegative and 2 NAAT-positive/Western blot indeterminate). Third
      generation testing correctly detected antibody in 34 specimens (55%; 95%
      confidence interval (CI): 42-67); Multispot detected antibody in 16 (26%; 95% CI:
      16-38). Of the 62 specimens, 33 (53%) had sufficient quantity for further
      testing. Rapid test sensitivities for early HIV infection ranged from 22-33%
      compared with 55-57% for the third-generation assay and 76-88% for the fourth
      generation tests. CONCLUSIONS: Many rapid HIV tests failed to detect half of the
      early HIV infection cases in whom antibody was present. Programs that screen high
      incidence populations with rapid tests should consider supplemental testing with
      NAAT or other antigen-based tests. These data support the need for more sensitive
      antigen-based point-of-care screening tests for early HIV infection.

PMID- 22381920
TI  - An integrated approach to the exposome.

PMID- 22381922
TI  - A new protein graph model for function prediction.
AB  - As several structural proteomic projects are producing an increasing number of
      protein structures with unknown function, methods that can reliably predict
      protein functions from protein structures are in urgent need. In this paper, we
      present a method to explore the clustering patterns of amino acids on the 3
      dimensional space for protein function prediction. First, amino acid residues on
      a protein structure are clustered into spatial groups using hierarchical
      agglomerative clustering, based on the distance between them. Second, the protein
      structure is represented using a graph, where each node denotes a cluster of
      amino acids. The nodes are labeled with an evolutionary profile derived from the
      multiple alignment of homologous sequences. Then, a shortest-path graph kernel is
      used to calculate similarities between the graphs. Finally, a support vector
      machine using this graph kernel is used to train classifiers for protein function
      prediction. We applied the proposed method to two separate problems, namely,
      prediction of enzymes and prediction of DNA-binding proteins. In both cases, the
      results showed that the proposed method outperformed other state-of-the-art
      methods.

PMID- 22381921
TI  - Evaluation of disease and viral biomarkers as triggers for therapeutic
      intervention in respiratory mousepox - an animal model of smallpox.
AB  - The human population is currently faced with the potential use of natural or
      recombinant variola and monkeypox viruses as biological weapons. Furthermore, the
      emergence of human monkeypox in Africa and its expanding environs poses a
      significant natural threat. Such occurrences would require therapeutic and
      prophylactic intervention with antivirals to minimize morbidity and mortality of
      exposed populations. Two orally-bioavailable antivirals are currently in clinical
      trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the
      DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these
      drugs have previously been evaluated in the ectromelia/mousepox system; however,
      the trigger for intervention was not linked to a disease biomarker or a specific
      marker of virus replication. In this study we used lethal, intranasal, ectromelia
      virus infections of C57BL/6 and hairless SKH1 mice to model human disease and
      evaluate exanthematous rash (rash) as an indicator to initiate antiviral
      treatment. We show that significant protection can be provided to C57BL/6 mice by
      CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We
      also show that significant protection can be provided to SKH1 mice treated with
      CMX001 at day 3 post infection or earlier, but this is four or more days before
      detection of rash (ST-246 not tested). Although in this model rash could not be
      used as a treatment trigger, viral DNA was detected in blood by day 4 post
      infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection 
      thus providing robust and specific markers of virus replication for therapy
      initiation. These findings are discussed in the context of current respiratory
      challenge animal models in use for the evaluation of poxvirus antivirals.

PMID- 22381923
TI  - Inflammation is related to unbalanced cardiac autonomic functions in
      hypertension: an observational study.
AB  - OBJECTIVE: Inflammation plays a role both in the mechanisms leading to
      hypertension alone and in the mechanisms leading to atherosclerosis with
      hypertension. Previous studies have shown the relationship between the autonomic
      functions and inflammatory system activation. The aim of the study was to
      evaluate the relationship between inflammation and cardiac autonomic functions in
      hypertensive patients. METHODS: One hundred twenty one hypertensive patients
      (mean age 59 +/- 11 years, 60 male) and 34 healthy volunteers (mean age 58 +/- 11
      years, 18 male) were included in the present cross-sectional observational study.
      The 24-hour ambulatory electrocardiogram recordings were taken using Pathfinder
      Software. The heart rate variability (HRV) analysis was performed using time
      domain parameters using the same software. Heart rate turbulence (HRT)
      parameters, turbulence onset and turbulence slope were calculated with HRT
      software. Statistical analysis was performed using unpaired t-test or Mann
      Whitney U test, one-way ANOVA or Kruskal-Wallis analysis of variance, Chi-square
      test, and Spearman rank order correlation analysis. The association of
      hypertension with high sensitivity C-reactive protein (hs-CRP), HRV and HRT was
      analyzed after adjustment for confounding variables as age and creatinine levels.
      RESULTS: The mean hs-CRP was higher, HRV was slightly reduced while HRT was
      markedly blunted in hypertensive patients in comparison with control group [SDNN;
      132 +/- 28 vs. 112 +/- 34 msec, RMSSD; 27 (23-35) vs. 22 (16-28) msec, TO; -2.80
      +/- 2.15 vs. -0.96 +/- 2.36%, TS; 7.56 (5.24-10.60) vs. 4.65 (2.44-7.26) msec/RR,
      p<0.01 for all]. All of the HRV and HRT parameters were more deteriorated in the
      highest tertile hs-CRP group [SDNN; 93 +/- 34 msec, RMSSD; 17 (13-22) msec, TO;
      0.03 +/- 2.22%, TS; 2.43 (1.84-3.89) msec/RR, p<0.05 for all]. There were
      correlations between hs-CRP and HRV and HRT parameters (SDNN; r=-0.690, RMSSD; r=
      0.277, TS; r:-0.417, TO; r=0.267, p<0.05 for all). CONCLUSION: There is an
      inflammatory process in hypertensive patients and inflammation is related with
      unbalanced cardiac autonomic functions.

PMID- 22381924
TI  - Validity of the Turkish version of the medication adherence self-efficacy scale
      short form in hypertensive patients.
AB  - OBJECTIVE: Study purpose was to examine the validity of a 13-item short form of
      the Medication Adherence Self-Efficacy Scale-Short Form (MASES-SF) in an
      independent sample of 150 hypertensive Turkish patients. METHODS: This is a
      methodological study and 150 adult patients, who are receiving medication for
      hypertension in the last one year, were included as the study sample. The sample
      of the study was chosen with the method of simple random sampling. The study was
      conducted between October 25, 2010 and December 31, 2010 at Family Health Center
      (FHC). In this study, exploratory and confirmatory factor analyses were used for
      psychometric evaluation. Cronbach's alpha coefficient was used to evaluate the
      reliability of the scale. RESULTS: Confirmatory factor analysis showed that all
      goodness indexes were at acceptable quality: chi(2)=61.72, df=65, p>0.05,
      GFI=0.99, CFI=1.00, RMSA=0.00. Reliability coefficient of the Turkish adaptation
      of MASES-SF was found as 0.94 and item-total correlations ranged between 0.63 -
      0.80. [corrected]. Patients with uncontrolled hypertension had lower self
      efficacy scores compared to those with normal blood pressure. CONCLUSION: This
      result indicated that the preliminary criterion validity is adequate.
      Psychometric testing demonstrated satisfactory internal consistency and validity
      of the instrument for patients in the study group. It can be used confidently in
      determining and testing interventions to improve medication adherence self
      efficacy perceptions and behaviors in hypertensive Turkish patients. The MASES-SF
      is brief, quick to administer, and capture useful data on medication adherence
      self-efficacy in hypertensive patients.

PMID- 22381925
TI  - Analysis of maximum P-wave duration and dispersion after percutaneous closure of
      atrial septal defects: comparison of two septal occluders.
AB  - OBJECTIVE: Amplatzer septal occluder (ASO) is the most widely used device for
      closure of atrial septal defect (ASD). Figulla septal occluder (FSO) is a similar
      device to ASO with some structural innovations. The aim of study is to assess the
      maximum P-wave duration (Pmax) and dispersion (Pd) in patients who underwent ASD
      closure with both devices, to determine the effects of structural innovations on
      atrial electrical inhomogeneity. METHODS: The study is a retrospective cohort
      analysis. Between December 2005 and March 2010, 121 patients underwent
      percutaneous closure of secundum ASD were included in this study. FSO was used in
      79 patients, ASO in 42 patients. Pmax and Pd were measured on the surface
      electrocardiography before and soon after procedure. For comparison of P-wave
      parameters initially and after procedure paired t-test was used. Correlation
      analysis was performed using Pearson correlation test. RESULTS: Pmax and Pd were
      significantly increased immediate after procedure (p<0.001). In FSO and ASO group
      pre/postprocedural Pd were 38.3 +/- 2.7/ 44.1 +/- 2.7 msec and 37.5 +/- 2.5/ 50.1
      +/- 2.2 msec respectively. ASO group had a greater postprocedural Pmax and Pd
      (p<0.001). Left and right atrial disc diameter and device size were the strongest
      correlates of Pd (r=0.52, p<0.001; r=0.58, p<0.001; r=0.35, p=0.001,
      respectively). Moderate correlation was found between pre-intervention Pd and age
      (p=0.008). CONCLUSIONS: Pmax and Pd were significantly increased soon after
      atrial septal defect closure procedure in both devices. Pd is significantly lower
      in patients closed with FSO device. Difference may be due to the distinctive
      texture of devices. There was no significant difference in terms of clinically
      apparent arrhythmia after closure with both device types.

PMID- 22381926
TI  - Does the surgical technique used in the orthotopic heart transplant affect the
      results regarding the rhythm?
AB  - OBJECTIVE: The aim of this study was to compare the requirement for temporary and
      permanent pacemaker insertion and the incidence of the problems regarding the
      rhythm following heart transplantation with the bicaval or biatrial technique in
      the early postoperative period. METHODS: Sixty-one patients underwent orthotopic
      heart transplantation between the dates of September 1989 and December 2008 in
      our clinics were included to the study. The study was designed as retrospective
      analysis, and all data were collected from hospital records. The transplantation
      was performed by using standard biatrial method in 28 of the patients, by using
      bicaval anastomosis method in 33 of the patients. Statistical analyses were
      performed using Chi-square, Fischer's exact and Mann-Whitney U tests. Predictors
      of temporary and permanent pacemaker insertion were analyzed using logistic
      regression analysis. RESULTS: In the biatrial group, the temporary pacemaker
      requirement (p<0.05), left bundle branch block (LBBB) (p<0.01) and
      atrioventricular block (AV block) (p<0.05) were observed statistically
      significantly more than in bicaval anastomosis group. In addition, in the
      biatrial group, one patient needed implantation of permanent pacemaker and one
      patient-implantable cardioverter defibrillator. On the postoperative
      echocardiographic evaluation, in the patients operated with the bicaval
      technique, the tricuspid (p<0.01) and mitral insufficiency (p<0.01) were observed
      significantly less. In the logistic regression analysis, hypertension (OR: 1.053,
      95% CI: 1.019-1.176, p<0.05), donor age (OR: 1.016, 95% CI: 1.023-1.038, p<0.05)
      and application of the operation with the biatrial technique (OR: 10.287, 95% CI:
      1.298-91.278, p<0.01) were determined as the risk factors requiring the temporary
      pacemaker usage. In the bicaval group, arrhythmia (ventricular and atrial
      premature beats) and atrioventricular valve insufficiency were observed less, the
      rhythm returned to normal in an earlier period. CONCLUSION: Biatrial surgical
      technique, donor age and hypertension were determined as significant predictors
      of temporary pacemaker insertion in the orthotopic heart transplantation.
      Atrioventricular block, left bundle branch block, and arrhythmia frequency was
      significantly less in the bicaval group. In terms of factors affecting morbidity,
      the bicaval technical results were found superior than biatrial technique.

PMID- 22381927
TI  - [Non-invasive mechanical ventilation therapy in patients with heart failure].
AB  - Non-invasive mechanical ventilation (NIMV) therapy in patients with acute heart
      failure (HF) improves left ventricular functions via decreasing left ventricular
      afterload and reduces intubation rate and short-term mortality. In patients with
      chronic HF, NIMV therapy eliminates central and obstructive apneas and Cheyne
      Stokes respiration, and improves morbidity. There are essentially three modes of
      NIMV that are used in the treatment of HF: Continuous positive airway pressure
      (CPAP), bilevel positive airway pressure (BIPAP) and adaptive servo-ventilation
      (ASV). Hereby, NIMV therapy in patients with acute and chronic HF is reviewed as
      well as methods, indications, effectiveness and complications.

PMID- 22381928
TI  - Identification of three H1N1 influenza virus groups with natural recombinant
      genes circulating from 1918 to 2009.
AB  - In this study, we identify a recombinant pb1 gene, a recombinant MP segment and a
      recombinant PA segment. The pb1 gene is recombined from two Eurasia swine H1N1
      influenza virus lineages. It belongs to a H1N1 swine clade circulating in Europe
      and Asia from 1999 to 2009. The mosaic MP segment descends from H7 avian and H1N1
      human virus lineages and pertains to a large human H1N1 virus family circulating
      in Asia, Europe and America from 1918 to 2007. The recombinant PA segment
      originated from two swine H1N1 lineages is found in a swine H1N1 group prevailing
      in Asia and Europe from 1999 to 2003. These results collectively falsify the
      hypothesis that influenza virus do not evolve by homologous recombination. Since
      recombination not only leads to virus genome diversity but also can alter its
      host adaptation and pathogenecity; the genetic mechanism should not be neglected
      in influenza virus surveillance.

PMID- 22381930
TI  - Tobacco control: time to protect children.

PMID- 22381929
TI  - Protein kinase PKR catalytic activity is required for the PKR-dependent
      activation of mitogen-activated protein kinases and amplification of interferon
      beta induction following virus infection.
AB  - The protein kinase regulated by RNA (PKR) enhances both activation of mitogen
      activated protein kinases and the induction of interferon beta (IFN-beta) by
      measles virus defective in C-protein expression (C(ko)). Here we used
      complementation of human cell lines stably deficient in PKR (PKR(kd)) to probe
      the basis of these PKR-mediated responses. We found that PKR(kd) HeLa and amnion
      U cell lines were defective for virus-mediated activation of IFN induction
      signaling components compared to PKR-sufficient control cells. Complementation of
      PKR(kd) cells with wildtype PKR, but not with PKR mutants defective in either
      catalytic activity or dsRNA-binding activity, restored JNK, p38 and ATF-2
      phosphorylation and enhanced IFN-beta induction following infection. By contrast
      to mammalian PKR, the Z-DNA binding domain-containing fish homologue of PKR, PKZ,
      lacked the capacity to enhance C(ko) virus-mediated IFN-beta induction.
      Furthermore, inhibition of virus growth was observed with C(ko)-infected PKR(kd)
      cells complemented with PKR but not with PKZ.

PMID- 22381931
TI  - Neuroblastoma stage 4S: a multifocal stem-cell disease of the developing neural
      crest.

PMID- 22381932
TI  - Ginger: the root of cancer therapy?

PMID- 22381933
TI  - Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for
      invasive or lethal recurrence.
AB  - By comparison with ovarian carcinomas, borderline ovarian tumours are
      characterised clinically by superior overall survival, even in women with
      peritoneal spread. In this Review, we aimed to clarify the histological and
      clinical factors potentially defining a high-risk group in whom disease is likely
      to evolve to invasive disease. Invasive peritoneal implants (in serous borderline
      ovarian tumours) and residual disease after surgery were the two factors clearly
      identified. Other factors are controversial owing to increased risk of invasive
      recurrence: micropapillary patterns in serous borderline ovarian tumour,
      intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous
      lesions, and use of cystectomy in mucinous borderline ovarian tumours. The
      pathologist has a pivotal role in assessment of the borderline nature of ovarian
      tumours and in identification of high-risk criteria, most of which are
      histological. But, reproducibility of the histological interpretation of some of
      these potential criteria--eg, classification of peritoneal implants (particularly
      in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and
      intraepithelial carcinoma in mucinous borderline ovarian tumours--remains
      unclear, and should be investigated.

PMID- 22381934
TI  - Development and experimental medicine applications of PET in oncology: a
      historical perspective.
AB  - Nearly 90 years of scientific research have led to the use of PET and the ability
      to forge advances in the field of oncology. In this Historial Review we outline
      the key developments made with this imaging technique, including the evolution of
      cyclotrons and scanners, together with the associated advances made in image
      reconstruction, presentation, analysis of data, and radiochemistry. The
      applications of PET to experimental medicine are summarised, and we cover how
      these are related to the use and development of PET, especially in the assessment
      of tumour biology and pharmacology. The use of PET in clinical oncology and for
      tissue pharmacokinetic and pharmacodynamic studies as a means of supporting drug
      development is detailed. The current limitations of the technology are also
      discussed.

PMID- 22381935
TI  - Priorities for cancer prevention: lifestyle choices versus unavoidable exposures.
AB  - Although cancer prevention in the USA and other developed countries focuses on
      disease attributable to lifestyle factors such as smoking, alcohol intake, sun
      exposure, and obesity, cancer caused by involuntary exposures is a concern. The
      term environmental is ambiguously used to distinguish between lifestyle and
      unavoidable exposures. The general community is said to be vulnerable to
      carcinogens encountered in pollution, contaminated food, and consumer products.
      In view of these concerns, assessments of the carcinogenicity of particular
      chemicals are of little assistance in prevention of cancer. Appraisal of cancer
      attributable to widespread and localised pollution, pesticides, endocrine
      disrupting chemicals, and consumer products yields diverse outcomes, from
      established causation to absence of harm. The precautionary principle is not a
      practicable approach for unknown carcinogenic risks. Procedures for individuals
      to reduce exposure to recognised or suspect carcinogens in consumer products are
      not effective measures for cancer prevention. Anxiety concerning insidious cancer
      causation could divert attention from proven means of cancer prevention.

PMID- 22381936
TI  - CT colonography screening.

PMID- 22381937
TI  - Breast cancer in Brazil: present status and future goals.
AB  - Breast cancer is the most common cancer in women worldwide and 70% of breast
      cancer deaths occur in women from low-income and middle-income countries. Latin
      America has about 115,000 new cases of disease every year, with about 50,000
      arising in Brazil. We examined the present status of breast cancer in Brazil as
      an example of the health effects of geographical, ethnic, and socioeconomic
      diversities on delivery of care. Our goal was to identify deficiencies that could
      be responsible for disparities in survival from breast cancer. We searched the
      English and Portuguese published work and reviewed national databases and
      Brazilian publications. Although the availability of publications specific to
      Brazil is low in general, we identified several factors that could account for
      disparities: delays in diagnosis due to low cancer awareness and implementation
      of mammography screening, unknown quality of surgery, and restricted access to
      radiotherapy and modern systemic therapies.

PMID- 22381938
TI  - Growth of InAs/InAsSb heterostructured nanowires.
AB  - We report the growth of InAs/InAs(1-x)Sb(x) single and double heterostructured
      nanowires by Au-assisted chemical beam epitaxy. The InAs(1-x)Sb(x) nanowire
      segments have been characterized in a wide range of antimony compositions.
      Significant lateral growth is observed at intermediate compositions (x ~ 0.5),
      and the nucleation and step-flow mechanism leading to this lateral growth has
      been identified and described. Additionally, CuPt ordering of the alloy has been
      observed with high resolution transmission electron microscopy, and it is
      correlated to the lateral growth process. We also show that it is possible to
      regrow InAs above the InAsSb alloy segment, at least up to an intermediate
      antimony composition. Such double heterostructures might find applications both
      as mid-infrared detectors and as building blocks of electronic devices taking
      advantage of the outstanding electronic and thermal properties of antimonide
      compound semiconductors.

PMID- 22381939
TI  - Multiple lectin detection by cell membrane affinity binding.
AB  - Assuming that lectins evolved to recognise relatively complex and branched
      oligosaccharides or parts of them, rather than simple sugars, a procedure based
      on lectin affinity binding to isolated erythrocyte (or any other cell type)
      membranes is proposed. This methodology was validated using six pure commercial
      lectins, as well as lectins from total protein extracts of Arbutus unedo leaves.
      All commercial lectins, as well as five polypeptides from A. unedo leaves bound
      to the glycosylated membrane receptors and were eluted by the corresponding
      sugars. When compared to the standard affinity chromatography procedure involving
      an individual sugar bound to a solid matrix, the new method provides a single
      step, effective detection method for lectins and allows the rapid screening of
      their profile present in any unknown protein solution, indicates their biological
      carbohydrate affinities as well as their sugar specificities (if any), enables
      the simultaneous analysis of a large number of samples, does not require any pre
      purification steps, permits detection of additional lectins and provides data
      which are more relevant from the physiological point of view.

PMID- 22381940
TI  - Decisions beyond boundaries: when more information is processed faster than less.
AB  - Bounded rationality models usually converge in claiming that decision time and
      the amount of computational steps needed to come to a decision are positively
      correlated. The empirical evidence for this claim is, however, equivocal. We
      conducted a study that tests this claim by adding and omitting information. We
      demonstrate that even an increase in information amount can yield a decrease in
      decision time if the added information increases coherence in the information
      set. Rather than being influenced by amount of information, decision time
      systematically increased with decreasing coherence. The results are discussed
      with reference to a parallel constraint satisfaction approach to decision making,
      which assumes that information integration is operated in an automatic, holistic
      manner.

PMID- 22381941
TI  - Crystallization from the micellar phase of imidazolium-based cationic
      surfactants.
AB  - The self-assembly and phase behavior of the aqueous dispersions consisting of the
      cationic surfactant, 1-hexadecyl-3-methylimidazolium chloride (C(16)mimCl), were
      studied by differential scanning calorimetry, synchrotron small- and wide-angle X
      ray scattering, freeze-fracture electron microscopy, polarizing optical
      microscopy, and Fourier transform infrared spectroscopy. We found that the
      crystallization of C(16)mimCl upon cooling is strongly concentration-dependent.
      At low concentrations (10-25 wt%), the samples change directly from a spherical
      micellar solution to a lamellar crystalline phase. While at high concentrations
      (50-67 wt%), the initial cylindrical micelles first convert to the lamellar gel
      phase and then to the lamellar crystalline phase. Particular efforts have been
      devoted to unveiling the submolecular mechanisms of the phase transition
      processes. The transformation from the initial micellar phase to the final
      crystalline phase upon cooling involves both an ordering rearrangement in the
      alkyl tails and a dehydrating process in the head region. At high concentrations,
      the transformation is divided into two steps, i.e., the gelation and subsequent
      crystallization processes, both involving evident rearrangements of the
      surfactant tails. Moreover, a significant dehydration of the surfactant head part
      takes place in the gelation step and a partial rehydration occurs in the
      crystallization step.

PMID- 22381942
TI  - Characterization of synthetic hematite (alpha-Fe2O3) nanoparticles using a multi
      technique approach.
AB  - The aim of this work was to investigate the surface structure of aqueous hematite
      dispersions characterized by a large variability of morphology and particle size
      combining structural investigations obtained from Atomic Force Microscopy (AFM)
      and Transmission Electron Microscopy (TEM) techniques with in vitro particle size
      distributions and zeta potential measurements from Dynamic Light Scattering (DLS)
      technique, and we achieved a self-consistent and detailed characterization of
      hematite particles whose sizes and morphologies could be correlated to the
      synthesis conditions (type of added anion, Al substitution and pH). Surface AFM
      characterization provided an accurate analysis of particle microstructure and
      also indicated that the growth of microcrystals followed different surface
      roughness. DLS, AFM, and TEM techniques furnished complementary information on
      the average particle dimensions, whose variation could be attributed to the
      morphological difference of hematites, ranging from platy to regular or irregular
      hexagonal or ellipsoidal shape. Finally, a correlation between the average
      particle dimensions and the measured zeta potential was also been found in
      aqueous dilute suspensions characterized by neither pH nor-ionic-strength
      control, for which a drop of zeta potential from positive to negative values was
      detected for hematite particle dimensions larger than a threshold size of ~150
      nm.

PMID- 22381943
TI  - Alcohol septal ablation in hypertrophic cardiomyopathy: an opportunity to be
      taken.

PMID- 22381944
TI  - The health care experiences of British pensioners migrating to Spain: a
      qualitative study.
AB  - BACKGROUND: Notwithstanding the importance of cross-border healthcare mobility
      for Member States very little research has been carried out to understand the
      experiences of those that move. This paper focuses on a type of patient mobility
      that has had a significant growth in the past decades. These are pensioners who
      have moved from Northern European countries to countries in the South. OBJECTIVE:
      To explore the health care experiences of British pensioners who have migrated to
      Spain. DESIGN: Qualitative study using in-depth interviews complemented with
      natural group discussions. PARTICIPANTS: Fifty-eight British retirees living in
      Spain and four that had returned to the UK from Spain. SETTING: Spanish
      Autonomous Communities of Valencia and Baleares and the UK. RESULTS: British
      pensioners reported high satisfaction with their experiences of Spanish health
      care, in contrast to their more negative experiences of other public services in
      Spain. The perceived high quality (assessed in terms of thoroughness of care and
      the cleanliness of facilities) and humanity of care provided were the pivotal
      features of health care encounters, at all levels of the health care system.
      Exceptions to the overall positive assessments were transport to health care
      facilities, personal care in hospitals, long term care, and the management of
      pain relief, which were compared unfavourably with the UK NHS. CONCLUSION: In
      contrast to the existing literature, which suggests widespread problems faced by
      migrant British pensioners in accessing health care, we identified high levels of
      satisfaction with services.

PMID- 22381945
TI  - Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and
      cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract.
AB  - Hepatocytes of a primary cell culture that are exposed to high glucose, insulin,
      and linoleic (LA) acid concentration respond with lipid accumulation, oxidative
      stress up to cell death. Such alterations are typically found in patients with
      non-alcoholic fatty liver disease (NAFLD). We used this cellular model to study
      the effect of an ethanolic Gynostemma pentaphyllum (GP) extract in NAFLD. When
      hepatocytes were cultured in the presence of high insulin, glucose, and LA
      concentration the extract completely protected the cells from cell death. In
      parallel, the extract prevented accumulation of triglycerides (TGs) and
      cholesterol as well as oxidative stress. Our data further demonstrate that GP
      stimulates the production of nitric oxide (NO) in hepatocytes and affects the
      molecular composition of the mitochondrial phospholipid cardiolipin (CL). We
      conclude that GP is able to protect hepatocytes from cell death, lipid
      accumulation, and oxidative stress caused by diabetic-like metabolism and
      lipotoxicity. Therefore, GP could be beneficial for patients with diabetes
      mellitus and NAFLD.

PMID- 22381946
TI  - Designing observation charts to optimize the detection of patient deterioriation:
      reliance on the subjective preferences of healthcare professionals is not enough.
AB  - AIM: Observation charts are critical to detecting patient deterioration. Research
      suggests their design has a dramatic impact on user performance in terms of
      failure rates for detecting abnormal vital signs and how quickly users can
      interpret recorded observations. In this study, we examined the design
      preferences of professional chart users to assess their alignment with objective
      performance data. In addition, we tested the assumptions of prior knowledge that
      chart designers appear to have made about chart users. METHODS: We conducted an
      online survey of health professionals (n=347). Participants answered questions
      about their observation chart design preferences in general, and were randomly
      assigned to evaluate one of nine specific charts. RESULTS: Chart users'
      preferences for design features were not always consistent with objective
      performance data. While some views concurred with empirical findings (e.g.,
      participants preferred to plot observations on a graph with graded colouring,
      where the colours corresponded with degrees of abnormality), others did not
      (e.g., participants preferred plotting blood pressure and pulse together on the
      same chart area, which the objective data suggest is problematic). Additionally,
      a substantial proportion of respondents were unfamiliar with some of the assumed
      knowledge required to interpret many charts (e.g., particular abbreviations).
      CONCLUSIONS: It is dangerous to rely solely on subjective opinions - even those
      of experienced health professionals - when developing patient observation charts,
      as optimal design may be counterintuitive and some preferences may merely reflect
      familiarity. Objective performance data is also required. In addition, the level
      of assumed knowledge required to use a chart should be minimized.

PMID- 22381947
TI  - Three-dimensional assessment of bilateral symmetry of the radius and ulna for
      planning corrective surgeries.
AB  - PURPOSE: The contralateral unaffected side is often used as a reference in
      planning a corrective osteotomy of a malunited distal radius. Two-dimensional
      radiographs have proven unreliable in assessing bilateral symmetry, so we
      assessed 3-dimensional configurations to assess bilateral symmetry. METHODS: We
      investigated bilateral symmetry using 3-dimensional imaging techniques. A total
      of 20 healthy volunteers without previous wrist injury underwent a volumetric
      computed tomography of both forearms. The left radius and ulna were segmented to
      create virtual 3-dimensional models of these bones. We selected a distal part and
      a larger proximal part from these bones and matched them with a mirrored computed
      tomographic image of the contralateral side. This allowed us to calculate the
      relative displacements (Deltax, Deltay, Deltaz) and rotations (Deltaphix,
      Deltaphiy, Deltaphiz) for aligning the left bone with the right bone segments. We
      investigated the relation between longitudinal length differences in radiuses and
      ulnas. RESULTS: Relative differences of the radiuses were (Deltax, Deltay,
      Deltaz): -0.81 +/- 1.22 mm, -0.01 +/- 0.64 mm, and 2.63 +/- 2.03 mm; and
      (Deltaphix, Deltaphiy, Deltaphiz): 0.13 degrees  +/- 1.00 degrees , -0.60 degrees
      +/- 1.35 degrees , and 0.53 degrees  +/- 5.00 degrees . The same parameters for
      the ulna were (Deltax, Deltay, Deltaz): -0.22 +/- 0.82 mm, 0.52 +/- 0.99 mm, 2.08
      +/- 2.33 mm; and (Deltaphix, Deltaphiy, Deltaphiz): -0.56 degrees  +/- 0.96
      degrees , -0.71 degrees  +/- 1.51 degrees , and -2.61 degrees  +/- 5.58 degrees .
      There is a strong relation between absolute length differences (Deltaz) between
      the radiuses and ulnas of individuals. CONCLUSIONS: We observed substantial
      length and rotational differences around the longitudinal bone axis in healthy
      individuals. Surgical planning using the unaffected side as a reference may not
      be as useful as previously assumed. However, including the length difference of
      the adjacent forearm bones can be useful in improving length correction in
      computer-assisted planning of radius or ulna osteotomies and in other
      reconstructive surgery procedures. CLINICAL RELEVANCE: Bilateral symmetry is
      important in reconstructive surgery procedures where the contralateral unaffected
      side is often used as a reference for planning and evaluation.

PMID- 22381948
TI  - Simultaneous intercostal nerve transfers to deltoid and triceps muscle through
      the posterior approach.
AB  - PURPOSE: This study reports the results of restoring the deltoid and triceps
      functions in patients with C5, C6, and C7 root avulsion injuries by
      simultaneously transferring 4 intercostal nerves to the anterior axillary nerve
      and the nerve to the long head of the triceps through the posterior approach.
      METHODS: Nine patients with C5, C6, and C7 root avulsion injuries underwent
      spinal accessory nerve transfer to the suprascapular nerve combined with transfer
      of the third and fourth intercostal nerves to the anterior axillary nerve for
      shoulder reconstruction. Simultaneous transfer of the fifth and sixth intercostal
      nerves to the radial nerve branch of the triceps was done to restore elbow
      extension. RESULTS: For shoulder function, 8 patients had M4 recovery and 1
      patient had M2 recovery. Average shoulder abduction and external rotation were 69
      degrees  and 42 degrees , respectively. For elbow extension, 3 patients achieved
      M3 recovery, 5 patients had M2 recovery, and 1 patient had M1 recovery.
      CONCLUSIONS: Reconstruction of 2 muscles with intercostal nerves is possible when
      both muscles act synergistically, such as shoulder abduction and elbow extension.
      Two intercostal nerves are adequate to transfer for deltoid reconstruction but
      not enough for elbow extension against gravity. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 22381949
TI  - The predictive validity of atypical neurovegetative depressive symptoms
      identified by the first principal component in the DUAG trial of moclobemide
      versus clomipramine.
AB  - OBJECTIVE: To investigate to what extent the primary depression subtype atypical
      depression can predict differential outcome of the mono-amino-oxidase inhibitor
      (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish
      University Antidepressant Group Study (DUAG). METHODS: In a randomised, double
      blind trial, a total of 117 patients with major depression were treated over 6
      weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal
      component analysis (PCA) was performed to identify atypical symptoms on the
      combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the
      Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was
      the subscale HAM-D(6) which contains the pure items of depression. RESULTS: PCA
      identified two items with loadings opposite to the other depression items within
      HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite
      (atypical neurovegetative symptoms). Patients with a positive score at baseline
      on these items were classified as having atypical depression. In total 13
      patients were classified as having atypical depression. Within this group of
      patients 8 received clomipramine and 5 patients received moclobemide. At endpoint
      the moclobemide treated patients had a significantly better response than the
      clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome.
      However, in the 104 patients classified as having typical depression clomipramine
      was superior to moclobemide (P=0.034), effect size 0.47. LIMITATIONS: The number
      of patients with atypical neurovegetative symptoms was very small and no placebo
      arm was included. CONCLUSIONS: It is very important to screen for atypical
      depression (increased duration of sleep/increased appetite) in the acute therapy
      of patients with major depression. Our results add to the body of evidence that
      monoamine oxidase inhibitors are superior to tricyclic antidepressants in this
      sub-group of patients.

PMID- 22381950
TI  - Gray matter abnormalities in patients with premenstrual dysphoric disorder: an
      optimized voxel-based morphometry.
AB  - BACKGROUND: Although brain neurochemistry is thought to play a role in the
      development of premenstrual dysphoric disorder (PMDD), neuroimaging studies of
      PMDD are sparse. We examined the extent to which gray matter (GM) abnormalities
      were present in women with PMDD compared to healthy controls. METHODS: 3.0T
      magnetic resonance imaging scans of 15 women with PMDD and 15 healthy controls
      were compared using optimized voxel-based morphometry (VBM) analysis. A
      regression analysis was used to assess the relationship between GM density and
      PMDD-symptom severity. RESULTS: Our results showed significantly increased GM
      density in the hippocampal cortex and significantly decreased GM density in the
      parahippocampal cortex among women with PMDD compared to healthy controls.
      However, these GM abnormalities were not significantly associated with the
      severity of PMDD. LIMITATION: Our inferences of the relationships between
      structural alterations and PMDD are drawn from a small sample, which may have
      increased the likelihood of type I error. CONCLUSIONS: GM abnormalities in limbic
      and paralimbic cortices were found to be associated with the pathophysiology of
      PMDD. Etiology of PMDD is likely related to emotional processing and self
      regulation. Our findings provide a basis of neurobiological model for PMDD.

PMID- 22381951
TI  - Life events and social rhythms in bipolar spectrum disorders: an examination of
      social rhythm sensitivity.
AB  - OBJECTIVES: To examine the presence of an underlying social rhythm sensitivity in
      individuals with bipolar spectrum disorders. METHODS: The present study examined
      the impact of life events on sleep loss and social rhythm disruption in 184
      individuals with bipolar spectrum disorders (BSD) compared to 197 demographically
      similar normal controls (NC) drawn from the Longitudinal Investigation of Bipolar
      Spectrum Disorders (LIBS) project. Life events data were obtained at three time
      points, each spaced four months apart, and included information on the intensity
      of the event (high or low), valence (negative or positive), and levels of sleep
      loss and social rhythm disruption brought about the event. We hypothesized that
      BSD participants would exhibit higher levels of social rhythm disruption and
      sleep loss than normal controls as a consequence of the same life events.
      RESULTS: BSD participants experienced significantly more social rhythm disruption
      and sleep loss following all classes of life events. LIMITATIONS: The cross
      sectional design of this study limits the strength of the conclusions that can be
      drawn, primarily cause and effect relationships between social rhythms and
      symptoms. CONCLUSIONS: Findings support the presence of an underlying social
      rhythm sensitivity in individuals with bipolar spectrum disorders. An additive
      effect of sleep loss and social rhythm disruption may contribute to subsequent
      mood symptomatology. Results from this study may inform early psychosocial
      interventions for at-risk individuals.

PMID- 22381953
TI  - The validity of the severity-psychosis hypothesis in depression.
AB  - BACKGROUND: Psychotic depression (PD) is classified as a subtype of severe
      depression in the current diagnostic manuals. Accordingly, it is a common
      conception among psychiatrists that psychotic features in depression arise as a
      consequence of depressive severity. The aim of this study was to determine
      whether the severity of depressive and psychotic symptoms correlate in accordance
      with this "severity-psychosis" hypothesis and to detect potential differences in
      the clinical features of PD and non-psychotic depression (non-PD). METHODS:
      Quantitative analysis of Health of the Nation Outcome Scales (HoNOS) scores from
      all patients admitted to a Danish general psychiatric hospital due to a severe
      depressive episode in the period between 2000 and 2010 was performed. RESULTS: A
      total of 357 patients with severe depression, of which 125 (35%) were of the
      psychotic subtype, formed the study sample. Mean HoNOS scores at admission
      differed significantly between patients with non-PD and PD on the items
      hallucinations and delusions (non-PD=0.33 vs. PD=1.37, p<0.001), aggression (non
      PD=0.20 vs. PD=0.36, p=0.044) and on the total score (non-PD=10.55 vs. PD=11.87,
      p=0.024). The HoNOS scores on the two items "depression" and "hallucinations and
      delusions" were very weakly correlated. LIMITATIONS: Diagnoses were based on
      normal clinical practice and not formalized research criteria. CONCLUSIONS: The
      symptomatology of PD and non-PD differs beyond the mere psychosis. Furthermore,
      severity ratings of depressive and psychotic symptoms are very weakly correlated.
      These findings offer further support to the hypothesis stating that the psychotic
      and non-psychotic subtypes of depression may in fact be distinct clinical
      syndromes.

PMID- 22381952
TI  - Longitudinal study of resilience and mental health in Marines leaving military
      service.
AB  - BACKGROUND: Despite a growing emphasis on psychological outcomes following
      military combat, few longitudinal studies have examined the combined role of risk
      and protective factors in the mental health of combat-exposed military personnel.
      This study characterizes the impact of resilience scale scores and combat
      exposure on mental health outcomes among Marines after separating from military
      service, along with intra-individual changes in mental health status. METHODS:
      Data were collected from longitudinal surveys of 475 active duty Marines
      attending a random sample of mandatory Transition Assistance Program workshops
      before leaving the military and responding to follow-up mail or web surveys an
      average of 6 months after returning to civilian life. RESULTS: Results revealed
      distinct risk and protective factors for those meeting screening criteria for
      mental health problems (depression, anxiety, and PTSD) and functional impairment
      at follow-up. Primary risk factors included experiencing higher levels of pre
      separation combat exposure; post-separation stress across multiple life domains;
      and experiencing multiple areas of pain post-separation. Protective factors
      include having higher scores on pre-separation resilience and perceived social
      support at follow-up indices. We also identified a number of factors associated
      with change in mental health status from baseline to follow-up. LIMITATIONS:
      Generality is limited by a lower than expected follow-up response rate and an
      exclusively Marine sample. CONCLUSION: The role of resilience appeared to have a
      greater impact on functional impairment than on mental health symptoms per se.
      Findings provide important input for enhancing training programs and services
      intended to promote adjustment from military to civilian life. Additional
      emphasis on social support and coping with stress-related issues are needed in
      support of combat veterans.

PMID- 22381954
TI  - Anxiety disorders in intimate partners and the quality of their relationship.
AB  - BACKGROUND: The aim of this study was to explain whether anxiety disorders
      presenting in one or both partners of a relationship can influence the latter and
      to what extent. METHODS: This study included 85 couples, where: 1) the male
      partner suffered from an anxiety disorder and female partner was free from this
      type of disorder (F((-))M((+)), n=20); 2) the female partner suffered from an
      anxiety disorder and the male partner was free from this type of disorder
      (F((+))M((-)); n=40); and 3) both partners were affected with anxiety disorders
      (F((+))M((+)), n=25). The quality of the relationship was assessed by both
      partners using three different scales: 1) Dyadic Adjustment Scale (DAS), 2)
      Family Attitude Scale (FAS), and 3) Marriage Success Scale (SPM). RESULTS: In
      case of the SPM scale, women from F((-))M((+)) group evaluated their marriages
      significantly compared to other groups. In case of males, the self-evaluated
      quality of marriage was the lowest in the case of individuals from F((+))M((+))
      group. In case of the DAS scale, women and men being free from anxiety disorders
      assessed the quality of their relationships significantly higher than other
      participants. The analyzed groups did not differ significantly in terms of mean
      values scored in the FAS scale. LIMITATIONS: The lack of a multifactorial
      analysis taking into account the effects of a variety of anxiety disorders.
      CONCLUSION: The presence of anxiety disorders in at least one partner negatively
      affects the quality of partner relationship. The couples where the female
      partners are affected are particularly fragile.

PMID- 22381955
TI  - Prevalence and correlates of the proposed DSM-5 diagnosis of Chronic Depressive
      Disorder.
AB  - CONTEXT: The draft proposal to add Chronic Depressive Disorder to DSM-5 will
      combine DSM-IV Dysthymic Disorder and Major Depressive Disorder, with chronic
      specifier, into a single diagnosis. OBJECTIVE: The objective of this study is to
      estimate the prevalence and correlates of the proposed DSM-5 diagnosis of Chronic
      Depressive Disorder using unit record data from the 2007 Australian National
      Survey of Mental Health and Wellbeing. DESIGN: Secondary analysis of a nationally
      representative household survey. SETTING: Urban and rural census tracts.
      PARTICIPANTS: One individual between the ages of 16 and 85 years from 8841
      households was interviewed for the survey. MAIN OUTCOME MEASURE: Lifetime
      prevalence estimates for chronic and non-chronic depression were determined using
      data from the World Health Organization's Composite International Diagnostic
      Interview, version 3.0 (WMH-CIDI 3.0). RESULTS: Chronic depression of at least
      two years' duration had a lifetime prevalence of 4.6% (95% CI: 3.9-5.3%) and was
      found in 29.4% (95% CI: 25.6-33.3%) of individuals with a lifetime depressive
      disorder. Higher rates of psychiatric co-morbidity (OR=1.42; 95% CI=1.26-1.61),
      older age (OR=1.04; 95% CI=1.02-1.05), a younger age of onset (OR=0.97; 95%
      CI=0.95-0.98) and more frequent episodes of depression (OR=1.75; 95% CI=1.07
      2.86) were found to be significant correlates of chronic depression. The first
      episode of depression for individuals with chronic depression often developed
      after the death of someone close (OR=2.38; 95% CI 1.16-5.79). CONCLUSIONS:
      Chronic depression is highly prevalent among community-residing persons and has a
      set of correlates that discriminate it from non-chronic depression. The
      distinction between chronic and non-chronic depression proposed for DSM-5, in the
      form of Chronic Depressive Disorder, seems to be warranted.

PMID- 22381956
TI  - A mechanistic model of lecithin:cholesterol acyltransferase activity exploits
      discoidal HDL composition and structure.
AB  - Lecithin:cholesterol acyltransferase (LCAT) activity towards discoidal HDL with
      apoA-I was analyzed in conjunction with re-evaluation of conformational stability
      of apoA-I (Sparks et al., 1993). The reaction at water-lipid interface involves
      the formation of acyl-enzyme and cholesterol (Chol) as a nucleophilic agent can
      compete with water at deacylation step. Raw data on apparent kinetic parameters
      for LCAT activity toward discoidal HDL with fixed (Sparks et al., 1995) or
      varying (Sparks et al., 1998) palmitoyloleoylphosphatidylcholine (POPC) content
      fit the kinetic equation derived. At the increase of Chol content in complexes
      with fixed POPC, interfacial dissociation constant K(d)(*) for LCAT penetration
      decreased and interfacial Michaelis constant K(m)(*) did not change. Also,
      differences in stability and unfolding cooperativity between two domains in apoA
      I molecule increased. At the increase of surface area of the complexes with
      varying POPC, K(d)(*) increased, while K(m)(*) decreased. For both lipidation
      states the rate constant of acyl-LCAT formation did not vary and any changes in
      K(m)(*) are postulated to originate from the change(s) in
      association/dissociation rate constants of enzyme-substrate complex. Then, at the
      increase of POPC, the LCAT-POPC complex becomes more stable. ApoA-I seems to
      "activate" substrate by increasing the exposure of POPC ester bond to active
      center of LCAT.

PMID- 22381957
TI  - Regulators of oxidative stress response genes in Escherichia coli and their
      functional conservation in bacteria.
AB  - Oxidative stress, through the production of reactive oxygen species, is a natural
      consequence of aerobic metabolism. Escherichia coli has several major regulators
      activated during oxidative stress, including OxyR, SoxRS, and RpoS. OxyR and SoxR
      undergo conformation changes when oxidized in the presence of hydrogen peroxide
      and superoxide radicals, respectively, and subsequently control the expression of
      cognate genes. In contrast, the RpoS regulon is induced by an increase in RpoS
      levels. Current knowledge regarding the activation and function of these
      regulators and their dependent genes in E. coli during oxidative stress forms the
      scope of this review. Despite the enormous genomic diversity of bacteria,
      oxidative stress response regulators in E. coli are functionally conserved in a
      wide range of bacterial groups, possibly reflecting positive selection of these
      regulators. SoxRS and RpoS homologs are present and respond to oxidative stress
      in Proteobacteria, and OxyR homologs are present and function in H(2)O(2)
      resistance in a range of bacteria, from gammaproteobacteria to Actinobacteria.
      Bacteria have developed complex, adapted gene regulatory responses to oxidative
      stress, perhaps due to the prevalence of reactive oxygen species produced
      endogenously through metabolism or due to the necessity of aerotolerance
      mechanisms in anaerobic bacteria exposed to oxygen.

PMID- 22381958
TI  - MiniArc single-incision sling in the office setting.
AB  - STUDY OBJECTIVE: To report MiniArc single-incision sling efficacy results in the
      office setting and the feasibility of performing the procedure in the office.
      DESIGN: Prospective, single-arm, nonrandomized, institutional review board
      approved study (Canadian Task Force classification II-2). SETTING: Three in
      office clinical sites in the United States. PATIENTS: Thirty-eight patients who
      underwent treatment of stress urinary incontinence using the MiniArc single
      incision sling. INTERVENTION: A MiniArc single-incision sling was placed in 38
      patients in an office-based setting under intravenous or oral sedation and/or
      local anesthesia. MEASUREMENTS AND MAIN RESULTS: Thirty-eight implant recipients
      were evaluated for effectiveness and safety via qualitative (Urinary Distress
      Inventory-Short Form [UDI-6] and Incontinence Impact Questionnaire-Short Form
      [IIQ-7]) and quantitative (1-hour pad-weight test and cough stress test)
      measurements at 3 clinical sites. Secondary outcome measures included procedure
      time, estimated blood loss, length of stay, perioperative complications, Wong
      Baker Faces Pain Scale, and adverse events. During the study, 38 women (mean [SD;
      95% CI] age, 48.1 (8.4; 45.3-50.8 years)) received slings. Mean procedure time
      was 10.6 minutes, estimated blood loss was 23.2 mL, and length of stay was 1.3
      hours. At discharge, the Wong-Baker pain score was 0.2 (0.0-2.0). At 2 years, 31
      patients were available for follow-up. Of these, 93.5% had normal findings on the
      cough stress test, and 90.3% had pad weight <1 g; and 90.6% and 87.5%,
      respectively, using last failure carried forward analysis in 32 patients. The UDI
      6 and IIQ-7 median scores showed a statistically significant decrease from
      baseline (p < .001). There were no reports of serious adverse events or of bowel,
      urethral, bladder, or major vessel perforation. CONCLUSION: The in-office
      experience suggests that implantation of a single-incision sling for treatment of
      stress urinary incontinence with the patient under intravenous or oral sedation
      and/or local anesthesia can be performed safely, with effective results. Thus,
      performing this procedure in an office setting is a viable option.

PMID- 22381959
TI  - Absence of mechanical hyperalgesia after exercise (delayed onset muscle soreness)
      in neonatally capsaicin-treated rats.
AB  - Delayed onset muscle soreness (DOMS) appears with some delay after unaccustomed,
      strenuous exercise, especially after lengthening contraction (LC). It is
      characterized by tenderness and movement related pain, namely muscular mechanical
      hyperalgesia. To clarify the involvement of C-fibers in this mechanical
      hyperalgesia, we examined whether DOMS could be induced in rats treated
      neonatally with capsaicin. We confirmed that a large portion of unmyelinated
      afferent fibers were lost in capsaicin treated rats. In these animals, LC failed
      to induce muscular mechanical hyperalgesia. mRNA of nerve growth factor (NGF) in
      the muscle, which plays a pivotal role in maintaining mechanical hyperalgesia,
      was upregulated in the capsaicin treated animals similar to the vehicle treated
      animals. These results demonstrate that C-fiber afferents are essential in
      transmitting the nociceptive information from exercised muscle in DOMS.

PMID- 22381960
TI  - Functional correlation between olfaction and various sectioning of the lateral
      olfactory tract.
AB  - The lateral olfactory tract (LOT) is a central olfactory pathway, and efferent
      projections from the olfactory bulb are conveyed to the olfactory-related
      cortical structures via the LOT. The purpose of the present study is to determine
      the exact site of the LOT causing functional impairment in animals. After
      ablation of the right olfactory bulb, rats received rostrocaudal transection
      injuries on the left LOT at different levels between the olfactory bulb and the
      middle cerebral artery. Olfactory function of LOT-transected rats was studied by
      examining their olfactory ability to discriminate between the smell of water and
      cycloheximide solution, a strong repellent for rodents. Rats were divided into
      two groups based on their olfactory discriminative abilities. The olfaction
      positive (+) group achieved 83%+/- 1% correct responses and the distances of the
      LOT-transected sites from the middle cerebral artery of this group ranged between
      0.8 and 2.4mm (n=8). The olfaction negative (-) group achieved 48%+/- 1% correct
      responses and the distances of the LOT-transected sites from the middle cerebral
      artery ranged between 2.5 and 4.2mm (n=10). From these data, we concluded that
      the site of the LOT critical for olfactory function is located approximately
      2.5mm from the middle cerebral artery.

PMID- 22381962
TI  - The woman at the end of the speculum.

PMID- 22381961
TI  - Development of metal-ion containing catalysts for the decomposition of
      phosphorothioate esters.
AB  - The widespread use of phosphorothioate esters as agricultural pesticides,
      chemical weapons and mechanistic probes in enzymology has sparked interest in the
      reactivity of these thio-substituted analogues of phosphate esters. In this brief
      account, we summarize the recent developments in our understanding of the
      mechanisms of hydrolysis (and solvolysis in methanol) of phosphorothioates
      containing a sulfur atom in the bridging and/or non-bridging position. A small
      number of highly efficient catalytic systems containing the metal ions La(III),
      Pd(II), Cu(II) and Zn(II) have been developed to promote the degradation of the
      various classes of phosphorothioate esters. The mechanisms of the base promoted
      solvolytic reactions in water and methanol and those of the metal catalyzed
      cleavage are presented, as well as a discussion of the energetics of the
      catalytic processes and other salient features. The aim of this review is to
      provide the reader with a contemporary physical organic description of
      phosphorothioate ester cleavage. This article is part of a Special Issue
      entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.

PMID- 22381963
TI  - Pain management for office-based surgery: expanding our flight envelope.

PMID- 22381965
TI  - Atrophic endometrium.

PMID- 22381964
TI  - Laparoscopic surgery for isolated nodal recurrence: appropriate for all patients
      or only a select few?

PMID- 22381966
TI  - Median umbilical ligament or vesicourachal diverticulum.

PMID- 22381967
TI  - AAGL practice report: practice guidelines for the diagnosis and management of
      submucous leiomyomas.
AB  - Submucous leiomyomas or myomas are commonly encountered by gynecologists and
      specialists in reproductive endocrinology and infertility with patients
      presenting with 1 or a combination of symptoms that include heavy menstrual
      bleeding, infertility, and recurrent pregnancy loss. There exists a variety of
      interventions that include those performed under hysteroscopic, laparoscopic and
      laparotomic direction; an evolving spectrum of image guided procedures, and an
      expanding number of pharmaceutical agents, each of which has value for the
      appropriately selected and counseled patient. Identification of the ideal
      approach requires the clinician to be intimately familiar with a given patient's
      history, including her desires with respect to fertility, as well as an
      appropriately detailed evaluation of the uterus with any one or a combination of
      a number of imaging techniques, including hysteroscopy. This guideline has been
      developed following a systematic review of the evidence, to provide guidance to
      the clinician caring for such patients, and to assist the clinical investigator
      in determining potential areas of research. Where high level evidence was
      lacking, but where a majority of opinion or consensus could be reached, the
      guideline development committee provided consensus recommendations as well.

PMID- 22381969
TI  - When will video-assisted and robotic-assisted endoscopy replace almost all open
      surgeries?
AB  - This article traces the development of laparoscopy, and establishment resistance
      to its emergence as the technique to replace almost all laparotomies.

PMID- 22381968
TI  - When will laparoscopy totally replace laparotomy?
AB  - This clinical opinion explores the current "zeitgeist" of minimally invasive
      gynaecological surgery (MIGS) as reflected in opinions expressed at the 40th AAGL
      conference held in Hollywood, Florida. It addresses concerns relating to the
      introduction of MIGS globally and the current position of robotic surgery in
      relation to conventional minimally invasive techniques like vaginal hysterectomy
      and minilaparotomy. It also explores challenges relating to MIGS in the
      healthcare environment of the 21st century.

PMID- 22381970
TI  - Combined conservative surgical and medical treatment of a uterocutaneous fistula.
AB  - Uterocutaneous fistula is a rare complication that may follow cesarean section.
      Herein is described a rare case of uterocutaneous fistula. The patient, a 28-year
      old woman with a history of American Society for Reproductive Medicine stage IV
      endometriosis (Douglas pouch obliteration), underwent a cesarean section at 25
      weeks of gestation (twin pregnancy). Postoperatively, the patient returned to the
      emergency service because of the appearance of pus through the cesarean section
      abdominal scar, and was treated for a subcutaneous abscess. Because drainage
      continued, the presence of a uterocutaneous fistula was suspected. Magnetic
      resonance imaging confirmed this diagnosis. Hysteroscopy clearly revealed the
      uterine neck of the fistula tract. Leuprolide acetate (gonadotropin-releasing
      hormone agonist) deposit suspension was administered subcutaneously monthly for 6
      months. Surgery via laparoscopy and laparotomy was performed. This combined
      medical and conservative surgical treatment was successful. At 6-month follow-up,
      hysteroscopy revealed a normal uterine cavity. We conclude that magnetic
      resonance imaging and hysteroscopy are helpful in diagnosis of uterocutaneous
      fistula. Conservative surgical treatment associated with medical therapy can be
      an efficient procedure in women who desire subsequent pregnancies.

PMID- 22381971
TI  - Gorlin syndrome: two unusual cases of recurrent, bilateral, multinodular,
      calcified ovarian fibromas with conservative surgical treatment.
AB  - Gynecologically, NBCCS is variously associated (14%-75% cases) to typically
      bilateral, multinodular, calcified, ovarian fibromas. We report 2 rare cases of
      unusually recurrent bilateral ovarian fibromas treated with conservative surgery.
      Preservation of the normal ovarian tissue is always recommended, even though
      there is the risk of recurrences, given the benign nature of the lesions and the
      young age of patients.

PMID- 22381972
TI  - Unusual trocar site metastasis in a uterine leiomyosarcoma after laparoscopic
      hysterectomy.
AB  - With widespread use of laparoscopy in patients with gynecologic malignancy,
      occasionally port-site metastasis is an item of concern. Herein we report a case
      of leiomyosarcoma of the uterus that metastasized to an accessory port after
      laparoscopic-assisted vaginal hysterectomy. A 46-year-old woman with a
      preoperative diagnosis of leiomyoma underwent laparoscopic-assisted vaginal
      hysterectomy. Final histopathologic findings revealed leiomyosarcoma. A
      postoperative abdominopelvic computed tomography scan demonstrated no evidence of
      metastatic tumor. The patient received 6 courses of combined chemotherapy
      consisting of cisplatin and ifosfamide. Follow-up computed tomography was
      performed because of pelvic pain at 4 months after treatment and revealed a
      recurrent pelvic tumor and a metastatic mass at previous right trocar site. At
      debulking surgery, a pelvic mass measuring 10 cm was observed, and a subcutaneous
      nodule measuring 4 cm was noted at the site of the right accessory port, with
      intact underlying peritoneum. After complete removal of both tumors, concurrent
      chemoradiation consisting of external radiotherapy and cisplatin was
      administered. Six months after the second surgery, a pelvic mass measuring 15 cm
      was observed. A second debulking surgical procedure was performed. However, the
      patient died of the disease 6 months after the second recurrence.

PMID- 22381973
TI  - Transvaginal ovarian cystectomy for adnexal torsion during pregnancy.
AB  - Ovarian torsion requiring surgical intervention in pregnancy is rare. Herein is
      reported a case of ovarian torsion that was managed by transvaginal ovarian
      cystectomy in a 27 week gravid patient.

PMID- 22381974
TI  - Magnetic resonance fistulogram demonstration of urethrovesicovaginal fistula in a
      case of mullerian agenesis due to traumatic urethral coitus.
AB  - Vesicovaginal fistula is not uncommon in women of childbearing age, and can occur
      due to a multitude of causes, the chief ones being infection and neoplasia. An
      extensive PUBMED search yielded only a few reports describing causation of such a
      lesion due to traumatic urethral coitus. The classic method to demonstrate such
      fistulas is by direct contrast-enhanced fistulography. Herein we report a case of
      urethrovesicovaginal fistula with mullerian agenesis caused by traumatic urethral
      coitus, as demonstrated using indirect magnetic resonance fistulography.

PMID- 22381975
TI  - Treatment of fallopian tube metastasis in cervical cancer after laparoscopic
      ovarian transposition.
AB  - A 40-year-old woman, gravida 2, para 2, with squamous cell carcinoma of the
      cervix, stage IIB, underwent ovarian transposition. Bilateral salpingectomy was
      performed as part of the operative technique. Histopathologic analysis revealed
      mucosal spread of the tumor to one of the fallopian tubes. The patient underwent
      radiation of the ovaries in their new location in addition to standard
      chemoradiotherapy to the pelvis. There has been no evidence of disease for more
      than 5 years. Inasmuch as performance of bilateral salpingectomy in ovarian
      transposition is not standard practice, the finding of fallopian tube metastasis
      presented a dilemma to the clinician. It remains to be proved whether the finding
      of metastasis to the fallopian tubes can be evidence for ovarian metastasis in
      grossly normal-appearing ovaries to validate this practice. Literature review
      demonstrates that fallopian tube metastasis is usually associated with
      endometrial involvement.

PMID- 22381976
TI  - Laparoscopic management of pregnancy in a patient with uterus didelphys.

PMID- 22381979
TI  - Letter to the editor.

PMID- 22381981
TI  - Electrochemical degradation of perfluorooctanoic acid (PFOA) by Ti/SnO2-Sb,
      Ti/SnO2-Sb/PbO2 and Ti/SnO2-Sb/MnO2 anodes.
AB  - Electrochemical decomposition of environmentally persistent perfluorooctanoic
      acid (PFOA) in aqueous solution was investigated over Ti/SnO(2)-Sb, Ti/SnO(2)
      Sb/PbO(2), and Ti/SnO(2)-Sb/MnO(2) anodes. The degradation of PFOA followed
      pseudo-first-order kinetics. The degradation ratios on Ti/SnO(2)-Sb, Ti/SnO(2)
      Sb/PbO(2), and Ti/SnO(2)-Sb/MnO(2) anodes achieved 90.3%, 91.1%, and 31.7%,
      respectively, after 90 min electrolysis at an initial 100 mg/L PFOA concentration
      at a constant current density of 10 mA/cm(2) with a 10 mmol/L NaClO(4) supporting
      electrolyte solution. The defluorination rates of PFOA on these three anodes were
      72.9%, 77.4%, 45.6%, respectively. The main influencing factors on
      electrochemical decomposition of PFOA over Ti/SnO(2)-Sb anode were evaluated,
      including current density (5-40 mA/cm(2)), initial pH value (3-11), plate
      distance (0.5-2.0 cm), and initial concentration (5-500 mg/L). The results
      indicated that PFOA (100 mL of 100 mg/L) degradation ratio and defluorination
      ratio achieved 98.8% and 73.9%, respectively, at the optimal conditions after 90
      min electrolysis. Under this optimal condition, the degradation rate constant and
      the degradation half-life were 0.064 min(-1) and 10.8 min, respectively. The
      intermediate products including short-chain perfluorinated carboxylic acids
      (PFCAs, C(2) ~ C(6)) and perfluorocarbons (C(2) ~ C(7)) were detected by
      electrospray ionization (ESI) mass spectrum. A possible electrochemical
      degradation mechanism of PFOA including electron transfer, Kolbe decarboxylation,
      radical reaction, decomposition, and hydrolysis was proposed. The electrochemical
      technique could be employed to degrade PFOA from contaminated wastewater as well
      as to reduce the toxicity of PFOA.

PMID- 22381982
TI  - Transformation of phenazone-type drugs during chlorination.
AB  - Chlorination is one of the most popular disinfection steps for water treatment in
      Europe. However, chlorine can react with pharmaceuticals and other
      micropollutants leading to either their elimination or by-products being formed.
      These by-products are frequently not identified and therefore the consequences of
      chlorination can be underestimated. In this work, the degradation of two
      analgesics and antipyretics, phenazone (antipyrine) and propyphenazone, during
      chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS).
      A quadrupole-time-of-flight (Q-TOF) system was used to follow the time course of
      the pharmaceuticals, and also used in the identification of the by-products. The
      degradation kinetics was investigated at different concentrations of chlorine (1
      10 mg/L), bromide (0-100 MUg/L) and sample pH (5.7-8.3) by means of a Box-Behnken
      experimental design. Depending on these factors, half-lives were in the ranges:
      0.9-295 s for phenazone and 0.4-173 s for propyphenazone. Also, it was observed
      that chlorine concentration was a significant factor for propyphenazone,
      resulting in increased degradation rate as it is increased. The transformation
      path of these drugs consisted mainly of halogenations, hydroxylations and
      dealkylations. After several days of reaction two derivatives remained stable for
      phenazone: chloro-hydroxy-phenazone and N-demethyl-chloro-hydroxy-phenazone and
      two for propyphenazone: N-demethyl-hydroxy-propyphenazone and N-demethyl-chloro
      hydroxy-propyphenazone. Moreover, experiments conducted with real water matrices,
      tap and surface water, showed that reaction, and formation of by-products, can
      take place both at the emission source point (household) and during drinking
      water production.

PMID- 22381983
TI  - Evidence-based backlash: the tale of drotrecogin alfa.

PMID- 22381985
TI  - Peripartum cardiomyopathy: review and practice guidelines.
AB  - Peripartum cardiomyopathy, a type of dilated cardiomyopathy of unknown origin,
      occurs in previously healthy women in the final month of pregnancy and up to 5
      months after delivery. Although the incidence is low-less than 0.1% of
      pregnancies -morbidity and mortality rates are high at 5% to 32%. The outcome of
      peripartum cardiomyopathy is also highly variable. For some women, the clinical
      and echocardiographic status improves and sometimes returns to normal, whereas
      for others, the disease progresses to severe cardiac failure and even sudden
      cardiac death. In acute care, treatment may involve the use of intravenous
      vasodilators, inotropic medications, an intra-aortic balloon pump, ventricular
      assist devices, and/or extracorporeal membrane oxygenation. Survivors of
      peripartum cardiomyopathy often recover from left ventricular dysfunction;
      however, they may be at risk for recurrence of heart failure and death in
      subsequent pregnancies. Women with chronic left ventricular dysfunction should be
      managed according to guidelines of the American College of Cardiology Foundation
      and the American Heart Association.

PMID- 22381986
TI  - Bispectral index values, sedation-agitation scores, and plasma Lorazepam
      concentrations in critically ill surgical patients.
AB  - BACKGROUND: Publications on the use of the bispectral index for sedation
      monitoring in the intensive care unit are increasing. However, few studies have
      involved correlation of bispectral index with serum drug concentrations.
      OBJECTIVES: To assess the degree of correlation between bispectral index values,
      scores on the Sedation-Agitation Scale, and steady-state serum concentrations of
      lorazepam. METHODS: A prospective open-label study of patients in a surgical
      intensive care unit who were receiving mechanical ventilation and continuous
      infusions of lorazepam for more than 24 hours. Bispectral index was measured (BIS
      XP, Aspect Medical, Norwood, Massachusetts) to assess patients' sedation. Sensors
      were applied and values recorded before and after stimulation (endotracheal
      suctioning). Concomitant plasma samples were obtained to measure lorazepam
      concentration and scores on the Sedation-Agitation Scale were recorded. RESULTS:
      Sixteen patients were studied. Correlations between plasma concentrations of
      lorazepam and measurements of bispectral index for 1, 2, and 3 minutes before
      endotracheal stimulation were poor (0.21, 0.29, and 0.25, respectively).
      Correlation of peak values for bispectral index (after stimulation) with plasma
      concentrations of lorazepam was 0.29. Correlations of scores on the Sedation
      Agitation Scale with the aforementioned values for bispectral index were
      similarly poor. Area under the curve for bispectral index values also correlated
      poorly with plasma concentration of lorazepam (0.19) and score on the Sedation
      Agitation Scale (0.10). CONCLUSIONS: The correlation between bispectral index and
      score on the Sedation-Agitation Scale was poor. Correlation between bispectral
      index and plasma concentration of lorazepam was modestly better, but insufficient
      for clinical utility.

PMID- 22381987
TI  - Effect of a computerized insulin dose calculator on the process of glycemic
      control.
AB  - BACKGROUND: Glycemic control is important to patients' outcomes. However, the
      process of maintaining glycemic control is risk laden and labor intensive for
      nurses. OBJECTIVES: To examine the effects of using a computerized insulin dose
      calculator to facilitate management of glycemic control for critically ill
      cardiac patients. METHODS: A prospective randomized controlled trial was
      conducted with a sample of 300 intensive care patients, 141 randomized to the
      calculator group and 159 in the control (paper protocol) group. A convenience
      sample of 44 intensive care nurses responded to a nurse satisfaction survey.
      RESULTS: A significantly higher percentage of glucose measurements were in the
      target range in the calculator group than in the control group (70.4% [SD, 15.2%]
      vs 61.6% [SD, 17.9%], Z = -4.423, P < .001), and glucose variance was
      significantly less in the calculator group (35.5 [SD, 18.3] mg/dL vs 42.3 [SD,
      21.2] mg/dL, Z = -3.845, P < .001). Fewer hypoglycemic events occurred in the
      calculator group (7 vs 18), although this difference was not statistically
      significant. Nurse satisfaction was higher for the calculator group than for the
      control group (8.4 [SD, 1.4] vs 4.8 [SD, 2.4], Z = -5.055, P < .001). Nurses'
      deviation from the protocol was also less in the calculator group than in the
      control group. CONCLUSIONS: Management of glycemic control and nurse satisfaction
      were improved with use of the dose calculator. Improving nurses' processes of
      care may improve nurses' use of time and patient care overall. Studies with
      larger sample sizes over time are needed to determine these relationships.

PMID- 22381988
TI  - Patient-specific and surgical characteristics in the development of pressure
      ulcers.
AB  - BACKGROUND: Implementation of the ruling on the Inpatient Prospective Payment
      System by the Centers for Medicare and Medicaid has challenged nurses to focus on
      the prevention of pressure ulcers. Despite years of research, pressure ulcers are
      still one of the most common complications experienced by patients in health care
      facilities. OBJECTIVE: To examine the relationship between patients'
      characteristics (age, sex, body mass index, history of diabetes, and Braden Scale
      score at admission) and care characteristics (total operating room time, multiple
      surgeries, and vasopressor use) and the development of pressure ulcers. METHODS:
      In a cohort study, data from the electronic medical records of 3225 surgical
      patients admitted to a Midwest hospital, from November 2008 to August 2009 were
      analyzed statistically to determine predictors of pressure ulcers. RESULTS: A
      total of 12% of patients (n = 383) had at least 1 pressure ulcer develop during
      their hospitalization. According to logistic regression analysis, scores on the
      Braden Scale at admission (P < .001), low body mass index (P < .001), number of
      vasopressors (P = .03), multiple surgeries during the admission (P < .001), total
      surgery time (P < .001), and risk for mortality (P < .001) were significant
      predictors of pressure ulcers. CONCLUSION: Scores on the Braden Scale at
      admission can be used to identify patients at increased risk for pressure ulcers.
      For other high-risk factors, such as low body mass index and long operative
      procedures, appropriate clinical interventions to manage these conditions can
      help prevent pressure ulcers.

PMID- 22381989
TI  - Logistics of renal replacement therapy: relevant issues for critical care nurses.

PMID- 22381990
TI  - Congenital anomaly.

PMID- 22381991
TI  - Monitoring patients receiving enteral feedings.

PMID- 22381992
TI  - Complications after cardiovascular surgery in a case of undiagnosed spinal-bulbar
      muscular atrophy (Kennedy disease).
AB  - Neurodegenerative diseases are often associated with life-threatening declines in
      respiratory and swallowing mechanisms. We report the case of a 70-year-old man
      who had postoperative dysphagia and respiratory failure that required
      reintubation after coronary artery bypass surgery. Impairment of the patient's
      speech, swallowing, and respiratory mechanisms identified during postoperative
      clinical and instrumental examinations was suggestive of a neurodegenerative
      disease. Genetic testing confirmed a diagnosis of spinal-bulbar muscular atrophy
      (Kennedy disease). This case report aims to highlight increased morbidity in
      patients with undiagnosed neuromuscular disorders in the critical care setting
      and the benefits of vigilant postoperative monitoring and multidisciplinary
      involvement throughout the care of complex patients.

PMID- 22381994
TI  - Monitoring for intolerance to gastric tube feedings: a national survey.
AB  - BACKGROUND: Confusion about how to assess for intolerance to feedings often
      results in unnecessary feeding interruptions. OBJECTIVES: To report findings from
      a national survey of methods used by critical care nurses to assess tolerance to
      gastric tube feedings and to discuss the findings in light of current enteral
      nutrition guidelines. METHODS: A paper-and-pencil survey was mailed to 1909
      members of the American Association of Critical-Care Nurses. In addition, the
      same survey was posted online in a newsletter circulated to association members.
      Results from both surveys were pooled for data analysis. RESULTS: A total of 2298
      responses were obtained; most respondents reported using a combination of methods
      to assess tolerance to gastric tube feedings (listening for bowel sounds,
      measuring gastric residual volumes, observing for abdominal distention/discomfort
      and for nausea and vomiting). More than 97% of the nurses reported measuring
      gastric residual volumes; the most frequently cited threshold levels for
      interrupting feedings were 200 mL and 250 mL. About 25% of the nurses reported
      interrupting feedings for gastric residual volumes of 150 mL or less; only 12.6%
      of the respondents reported allowing gastric residual volumes of up to 500 mL
      before interrupting feedings. CONCLUSIONS: Practice among the 2298 critical care
      nurses varied widely. Many of the survey respondents are practicing in ways that
      can unnecessarily diminish the delivery of calories to patients. Protocols based
      on current enteral nutrition guidelines must be developed and implemented in
      practice settings.

PMID- 22381993
TI  - Use of augmentative and alternative communication strategies by family members in
      the intensive care unit.
AB  - BACKGROUND: Little is known about communication between patients and their family
      members during critical illness and mechanical ventilation in the intensive care
      unit, including use of augmentative and alternative communication tools and
      strategies. OBJECTIVES: To identify (1) which augmentative and alternative
      communication tools families use with nonspeaking intensive care patients and how
      they are used, and (2) what families and nurses say about communication of family
      members with nonspeaking intensive care patients. METHODS: A qualitative
      secondary analysis was conducted of existing data from a clinical trial testing
      interventions to improve communication between nurses and intensive care
      patients. Narrative study data (field notes, intervention logs, nurses'
      interviews) from 127 critically ill adults were reviewed for evidence of family
      involvement with augmentative and alternative communication tools. Qualitative
      content analysis was applied for thematic description of family members' and
      nurses' accounts of patient-family communication. RESULTS: Family involvement
      with augmentative and alternative communication tools was evident in 44% of the
      93 patients who completed the parent study protocol. Spouses or significant
      others communicated with patients most often. Main themes describing patient
      family communication included (1) families being unprepared and unaware, (2)
      families' perceptions of communication effectiveness, (3) nurses deferring to or
      guiding patient-family communication, (4) patients' communication
      characteristics, and (5) families' experience with and interest in augmentative
      and alternative communication tools. CONCLUSIONS: Assessment by skilled bedside
      clinicians can reveal patients' communication potential and facilitate useful
      augmentative and alternative communication tools and strategies for patients and
      their families.

PMID- 22381995
TI  - Professional autonomy, collaboration with physicians, and moral distress among
      European intensive care nurses.
AB  - BACKGROUND: Discretionary autonomy is a key factor in enhanced patient outcomes
      and nurses' work satisfaction. Among nurses, insufficient autonomy can result in
      moral distress. OBJECTIVES: To explore levels of autonomy among European critical
      care nurses and potential associations of autonomy with nurse-physician
      collaboration, moral distress, and nurses' characteristics. METHODS: Descriptive
      correlational study of a convenience sample of 255 delegates attending a major
      European critical care conference in 2009. Respondents completed a self
      administered questionnaire with validated scales for nurses' autonomy, nurse
      physician collaboration, and moral distress. RESULTS: The mean autonomy score
      (84.26; SD, 11.7; range, 18-108) and the mean composite (frequency and intensity)
      moral distress score (73.67; SD, 39.19; range, 0-336) were both moderate. The
      mean collaboration score was 47.85 (SD, 11.63; range, 7-70). Italian and Greek
      nurses reported significantly lower nurse-physician collaboration than did other
      nurses (P < .001). Greek and German nurses reported significantly higher moral
      distress (P < .001). Autonomy scores were associated with nurse-physician
      collaboration scores (P < .001) and with a higher frequency of moral distress (P
      = .04). Associations were noted between autonomy and work satisfaction (P =
      .001). Frequency of moral distress was associated inversely with collaboration
      (rho = -0.339; P < .001) and autonomy (rho = -0.210; P = .01) and positively with
      intention to quit (rho = 0.257; P = .004). CONCLUSIONS: In this sample of
      European intensive care nurses, lower autonomy was associated with increased
      frequency and intensity of moral distress and lower levels of nurse-physician
      collaboration.

PMID- 22381997
TI  - Revision sinus surgery.
AB  - Revision sinus surgery for inflammatory disease has been revolutionized by
      endoscopic sinus surgery. Clinical trials have shown statistically significant
      positive outcome data for patient symptoms and quality of life, as well as
      improvements in objective findings on postoperative nasal endoscopy and computed
      tomography imaging for patients undergoing revision sinus surgery. The keys to
      successful revision surgery are adjunctive medical management, aggressive
      postoperative debridement, mucosal preservation, and removal of osteitic bone.
      Both the physician and patient should also understand the underlying disease
      process and comorbid factors so that anticipated postoperative outcomes can be
      met with realistic expectations.

PMID- 22381998
TI  - Endoscopic surgery of the nose and paranasal sinus.
AB  - Mucosal preservation is of paramount importance in the diagnosis and surgical
      management of the sinonasal tract. The endoscope revolutionized the practice of
      endoscopic nasal surgery. As a result, external sinus surgery is performed less
      frequently today, and more emphasis is placed on functional endoscopy and
      preservation of normal anatomy. Endoscopic surgery of the nose and paranasal
      sinus has provided improved surgical outcomes and has shortened the length of
      stay in hospital. It has also become a valuable teaching tool.

PMID- 22382001
TI  - Photo-induced growth of DNA-capped silver nanoparticles.
AB  - We report the photo-induced nucleation and growth of silver nanoparticles in
      aqueous solution in the presence of DNA oligomers. An organic dye (Cy5) was used
      as a photosensitizer to initiate the nanoparticle growth upon illumination with
      647 nm light. The formation of nanoparticles and growth kinetics were observed by
      extinction spectroscopy, dynamic light scattering, and transmission electron
      microscopy. Irradiation of the precursor solutions with light at the Cy5
      absorption maximum triggered the instantaneous formation of spherical particles
      with a metallic core ~15 nm in diameter. Remarkably, the particles feature
      significantly larger effective hydrodynamic diameters (35 nm) in solution,
      indicative of a DNA ad-layer on the nanoparticle surface. Centrifugation
      experiments confirmed that DNA was inseparably associated with the nanoparticles
      and indicated that DNA oligomers adsorb onto the nanoparticle surface during
      growth, playing the role of a capping agent. The introduced method is a fast and
      facile way to prepare DNA-capped silver nanoparticles in a single growth step.

PMID- 22381996
TI  - Ethanol suppresses phagosomal adhesion maturation, Rac activation, and subsequent
      actin polymerization during FcgammaR-mediated phagocytosis.
AB  - Clinical and laboratory investigations have provided evidence that ethanol
      suppresses normal lung immunity. Our initial studies revealed that acute ethanol
      exposure results in transient suppression of phagocytosis of Pseudomonas
      aeruginosa by macrophages as early as 3 h after initial exposure. Focusing on
      mechanisms by which ethanol decreases macrophage Fcgamma-receptor (FcgammaR)
      phagocytosis we targeted the study on the focal adhesion and cytoskeletal
      elements that are necessary for phagosome progression. Ethanol inhibited
      macrophage phagocytosis of IgG-coated bead recruitment of actin to the site of
      the phagosome, dampened the phosphorylation of vinculin, but had no effect on
      paxillin phosphorylation suggesting a loss in "phagosomal adhesion" maturation.
      Moreover, our observations revealed that FcgammaR-phagocytosis induced Rac
      activation, which was increased by only 50% in ethanol exposed cells, compared to
      175% in the absence of ethanol. This work is the first to show evidence of the
      cellular mechanisms involved in the ethanol-induced suppression of FcgammaR
      mediated phagocytosis.

PMID- 22382002
TI  - Activation of phospholipase A(2) by low levels of fluoride in THP1 macrophages
      via altered Ca(2+) and cAMP concentration.
AB  - Phospholipases (PLA's) participate in the regulation of physiological and
      pathological processes in the cell, including the release of pro-inflammatory
      mediators and stimulation of inflammatory processes. It is also well known that
      fluoride can increase the inflammatory reactions. Therefore we decided to examine
      the effect of fluorides in concentrations determined in human serum on cPLA(2)
      and sPLA(2) activity. The incubation of macrophages in fluoride solutions
      significantly increased the amount of synthesized cellular cAMP, intracellular
      calcium and sPLA(2) activity in a dose-dependent pattern. The cPLA(2) activity,
      estimated by the amount of released arachidonic acid, increased significantly
      when 10 MUM NaF was used. The results of our study suggest that fluoride may
      change the activity of phospholipases in macrophage cells. Probably, increased
      cAMP concentration activates protein kinase C (PKC) and thus stimulates PLA(2).
      cAMP also regulates the passage of Ca(2+) through ion channels, which
      additionally influence PLA(2) throughout Ca(2+)-calmodulin dependent protein
      kinase.

PMID- 22382003
TI  - Texture and moments-based classification of the acrosome integrity of boar
      spermatozoa images.
AB  - The automated assessment of the sperm quality is an important challenge in the
      veterinary field. In this paper, we explore how to describe the acrosomes of boar
      spermatozoa using image analysis so that they can be automatically categorized as
      intact or damaged. Our proposal aims at characterizing the acrosomes by means of
      texture features. The texture is described using first order statistics and
      features derived from the co-occurrence matrix of the image, both computed from
      the original image and from the coefficients yielded by the Discrete Wavelet
      Transform. Texture descriptors are evaluated and compared with moments-based
      descriptors in terms of the classification accuracy they provide. Experimental
      results with a Multilayer Perceptron and the k-Nearest Neighbours classifiers
      show that texture descriptors outperform moment-based descriptors, reaching an
      accuracy of 94.93%, which makes this approach very attractive for the
      veterinarian community.

PMID- 22382004
TI  - Historical perspective: the pathogenesis of sheep pox infection (1959-2012) and
      the contribution of Walter Plowright.

PMID- 22382005
TI  - Peripheral RAGE (receptor for advanced glycation endproducts)-ligands in normal
      pregnancy and preeclampsia: novel markers of inflammatory response.
AB  - Inflammatory response in preeclampsia (PE) is a key feature in its
      pathophysiology. Advanced Glycation Endproducts (AGEs), receptors for AGEs
      (RAGE), and RAGE ligands are involved in systemic inflammation in various
      pathological conditions. In this study, we measured serum RAGE ligands in normal
      pregnancy controls and PE patients. Levels of Carboxymethyl Lysine (CML), HMGB1
      and S100A12/EN-RAGE were measured in thirty-three normal pregnant women 3 times
      at 10-12 (1st measurement), 28 (2nd measurement), and 36 (3rd measurement) weeks
      during gestation for paired analysis. We also measured those in serum samples
      from 17 severe PE patients at admission using ELISA. Early onset (EO, <32 weeks)
      and late onset (LO, >=32 weeks) PE patients were compared with the 2nd and 3rd
      measurements of normal controls, respectively. CML and HMGB1 did not change
      during normal pregnancy. However, S100A12/EN-RAGE decreased from the 1st to 2nd
      measurement (P<0.0001). Across all PE patients, serum CML was unaltered, while
      HMGB1 significantly increased compared to 2nd (P=0.0002) and 3rd (P<0.0001)
      measurement as well as individually compared to both EO (P=0.018) and LO groups
      (P=0.0001). S100A12 in all PE patients increased over 2nd (P=0.0015) and 3rd
      (P=0.0002) measurements, although only LO was significantly increased compared to
      the 3rd measurement (P=0.0005). Our data suggest that patterns of serum RAGE
      ligand concentration indicate different inflammatory pathways in normal
      pregnancy, EO-PE, and LO-PE.

PMID- 22382006
TI  - Immunoregulatory gene polymorphisms in Japanese women with preterm births and
      periodontitis.
AB  - Many studies have reported an association between periodontal disease and preterm
      birth, although this remains controversial. Cytokines and antibodies produced to
      give resistance to infection can enter the bloodstream and cause preterm labor.
      We analyzed maternal genetic polymorphisms in various immunoregulatory genes that
      could affect both preterm birth and periodontitis. A total of 1099 women referred
      to the Department of Obstetrics and Gynecology, Niigata University Medical and
      Dental Hospital were candidates for participation, 424 of whom refused, and 553
      were excluded. The final number of subjects was 122 (51 with preterm birth, 71
      with term birth). Genomic DNA was isolated from venous blood, and 22
      polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10,
      TNFA, TNFRI, TNFRII, FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, FcgammaRIIIB, and
      FcalphaR. Within five days of labor, periodontal parameters were evaluated, and
      bacteria from subgingival plaque were detected using real-time PCR. There was no
      difference in the prevalence and degree of periodontitis between term and preterm
      births. Chi-squared tests showed that an age <33 years and FcalphaR(+56)T/C
      alleles were associated with preterm birth. Multiple logistic regression analysis
      represented a model with significant fitness in which four variables were
      associated with preterm birth: maternal age, number of Aggregatibacter
      actinomycetemcomitans, IL-6(-572)G/C, and FcalphaR(+56)T/C. In conclusion, there
      was no association between preterm birth and periodontitis in this study. A.
      actinomycetemcomitans, IL-6, and FcalphaR were suggested to be associated with
      preterm birth. Multiple logistic regression models with both genetic and
      environmental factors would be useful for evaluating susceptibility to preterm
      birth.

PMID- 22382007
TI  - Ras association domain family 1A: a promising prognostic marker in recurrent
      nonmuscle invasive bladder cancer.
AB  - The aim of this study was to investigate the value of RASSF1A methylation as a
      prognostic marker in bladder cancer. RASSF1A hypermethylation from 301 specimens
      of primary BC tissue was assessed using methylation-specific PCR. Among patients
      with recurrent NMIBC, RASSF1A methylation was identified as an independent
      predictor of cancer progression. INTRODUCTION: Aberrant methylation of promoter
      CpG islands is an important inactivation mechanism of tumor suppressors and tumor
      related genes. Ras association domain family 1A (RASSF1A) promoter
      hypermethylation was shown to be associated with bladder cancer (BC), but its
      prognostic value remains unclear. The aim of the present study was to investigate
      the value of RASSF1A methylation as a prognostic marker in BC. MATERIALS AND
      METHODS: Primary BC tissues were obtained from 301 patients and included 186
      specimens of nonmuscle invasive bladder cancer (NMIBC) and 115 specimens of
      muscle invasive bladder cancers (MIBC). RASSF1A hypermethylation was assessed
      using methylation-specific polymerase chain reaction (MS-PCR). The association
      between RASSF1A hypermethylation and clinicopathologic features, and the
      prognostic significance of RASSF1A hypermethylation were evaluated by Kaplan
      Meier and multivariate Cox regression analyses. RESULTS: RASSF1A promoter
      hypermethylation was detected in 33.6% of BCs and occurred more frequently in
      MIBC (46.1%) than in NMIBC (25.8%) (P < .001). In NMIBC, RASSF1A methylation was
      associated with advanced tumor stage (P = .026) and high grade (P < .001). Among
      patients with recurrent NMIBC, RASSF1A methylation was associated with shorter
      time to progression by Kaplan-Meier analysis (log-rank test; P = .004) and
      identified as an independent predictor of cancer progression by multivariate Cox
      regression analysis (hazard ratio [HR], 8.559; P = .014). CONCLUSIONS: Our
      results suggest that methylated RASSF1A may be a potential prognostic marker in
      patients with recurrent NMIBC.

PMID- 22382009
TI  - Importance of fibroblast growth factor receptor in neovascularization and tumor
      escape from antiangiogenic therapy.
AB  - Therapeutic inhibition of pathways involved in angiogenesis has become the
      standard of care in renal cell carcinoma (RCC). Most currently available
      antiangiogenic agents inhibit the vascular endothelial growth factor (VEGF)
      pathway. Although these drugs have produced exciting benefits, some tumors do not
      respond to these agents. In addition most if not all tumors that initially
      respond will eventually develop resistance. Tumor escape from antiangiogenic
      therapy may include various signaling pathways that are involved in angiogenesis,
      including the fibroblast growth factor (FGF) signaling pathway. Emerging
      preclinical data suggest that FGF and VEGF act distinctly and synergistically to
      promote tumor vascularization. The current review discusses the role of FGF
      signaling in resistance to anti-VEGF therapies and outlines potential therapeutic
      implications.

PMID- 22382008
TI  - Epidemiologic trends in renal cell carcinoma in the cytokine and post-cytokine
      eras: a registry analysis of 28,252 patients.
AB  - Advances in the targeted treatment of renal cell cancer (RCC) have shown
      improvements in survival in clinical trials and have largely replaced cytokine
      therapies as the standard of care. However it is unclear if these advances have
      translated to the general RCC population. We present a retrospective study of a
      large clinical cancer registry that demonstrates statistically significant
      improvements in survival in cancer patients, but the causes of this improvement
      are difficult to determine because of many confounders. BACKGROUND: Before 2004,
      advanced renal cell cancer (RCC) therapy consisted primarily of cytokines such as
      interferon and/or interleukin-2. Subsequently, randomized trials of targeted
      therapies have shown a survival benefit, leading to the approval of several new
      agents since 2004. Whether the survival benefit seen in highly selected patients
      accrued to these trials has already translated to the general RCC patient
      population is unclear. To explore this, a large RCC patient registry was
      evaluated for changes in outcome between the cytokine (1998-2003) and post
      cytokine (2004-2007) eras. METHODS: Data from the California Cancer Registry
      (CCR), a population-based cancer surveillance system, was used to retrospectively
      analyze 28,252 patients with RCC diagnosed between 1998 and 2007. Inter-era
      differences in clinical variables-including year of diagnosis, histologic
      characteristics, age, sex, race, stage, nephrectomy status, overall survival
      (OS), and cause-specific survival (CSS)-were assessed. Univariate and
      multivariate Cox models were used. RESULTS: Crude 3-year OS (68.2% vs. 74.6%; 2P
      < .001) and CSS (78.1% vs. 82.3%; 2P < .001) were significantly higher in the
      post-cytokine era. In multivariate analysis, the 3 strongest predictors for
      improved survival were localized disease (hazard ratio [HR], 18.1; 95% confidence
      interval [CI], 16.6-19.6), nephrectomy (HR, 2.87; 95% CI, 2.68-3.08), and clear
      cell histologic type (HR, 1.33; 95% CI, 1.22-1.44). CONCLUSIONS: In this analysis
      of a large RCC registry, there was an apparent increase in crude OS and CSS in
      the post-cytokine era compared with the cytokine era. Insufficient follow-up time
      in the post-cytokine era and a higher proportion of localized disease in that era
      confound the possibility of benefit derived from targeted therapies. Longer
      follow-up for patients treated in the post-cytokine era is necessary for a more
      robust comparison of long-term OS.

PMID- 22382010
TI  - Highly sensitive and rapid profiling method for carotenoids and their epoxidized
      products using supercritical fluid chromatography coupled with electrospray
      ionization-triple quadrupole mass spectrometry.
AB  - Epoxy carotenoids, which are products of carotenoid oxidation, are potential
      oxidative stress markers. However, it is difficult to profile epoxy carotenoids
      owing to their small amount and difficulty in their separation from hydroxy
      carotenoids. In this study, a high-performance analytical system based on
      supercritical fluid chromatography (SFC) coupled with tandem mass spectrometry
      (MS/MS) was developed for the simultaneous analysis of carotenoids and epoxy
      carotenoids. SFC is an effective separation technique for hydrophobic compounds,
      by which major carotenoids in human serum and their epoxidation products can be
      analyzed within 20 min. The use of MS/MS increased the sensitivity; the detection
      limit for each carotenoid was of the sub-fmol order. When the constructed method
      was applied to biological samples such as human serum and low-density lipoprotein
      (LDL), the precise detection of the target carotenoids was disturbed by several
      isomers. However, highly selective detection of epoxy carotenoids was performed
      by targeting product ions that were generated with a structure-specific neutral
      loss of 80Da. Furthermore, the sample volume needed for the analysis was only
      0.1ml for the serum, indicating the efficiency of this system in performing small
      scale analyses. Using the analytical system developed in this study, highly
      sensitive and selective analysis of epoxy carotenoids could be performed in a
      short time. These features show the usefulness of this system in application to
      screening analysis of carotenoid profiles that are easily modified by oxidative
      stress.

PMID- 22382011
TI  - High-throughput method for a kinetics analysis of the high-pressure inactivation
      of microorganisms using microplates.
AB  - Using microplates as pressure and cultivation vessels, a high-throughput method
      was developed for analyzing the high-pressure inactivation kinetics of
      microorganisms. The loss of viability from a high-pressure treatment, measured
      based on the growth delay during microplate cultivation, showed reproducibility
      with the conventional agar plate method and was applicable for the kinetics
      analysis.

PMID- 22382012
TI  - Biochemical profile of halophilous microalgae strains from high-andean extreme
      ecosystems (NE-Chile) using methodological validation approaches.
AB  - The main goal of this work is to characterize the biochemical profile of three
      halophilous microalgal strains isolated from extreme ecosystems in northern Chile
      to assess their potential as possible sources of technological and commercial
      advantages. A procedure for the validation of a routine method for determining
      the total protein, carbohydrate, lipid and chlorophyll a (Chl-a) contents in
      Chlorella fusca, Dunaliella salina and Spirulina sp. has been developed.
      Detection limits of 10.8 MUg/mg, 2.7 MUg/mg and 5.6 MUg/mg for total protein
      content and 3.5 MUg/mg, 1.8 MUg/mg and 8.8 MUg/mg for total carbohydrate content
      were determined in C. fusca, D. salina and Spirulina sp., respectively. Most of
      the biological macromolecule levels measured in the microalgae were in accordance
      with the magnitude of previously reported data for other strains of the same
      taxa. However, lower levels than expected of lipids and Chl-a were measured in C.
      fusca and Spirulina sp., which may be associated with an imbalance between
      specific growth rates and the rate of macromolecule synthesis. The protein values
      measured in Spirulina sp. (52.3 +/- 2.2 MUg/mg DW) were close to the lower limit
      of the range reported in the literature for non-halophilous strains of the same
      genus. Except for the Chl-a quantification procedure, the analytical methods for
      macromolecules had a high degree of repeatability and reproducibility. The
      variability among repeated measurements of Chl-a was associated with auto
      degradation processes during pigment extraction.

PMID- 22382013
TI  - Cloning, over-expression and characterization of an alkali-tolerant endo-beta-1,4
      mannanase from Penicillium freii F63.
AB  - A glycosyl hydrolase family 5 endo-beta-mannanase gene (man5F63) was cloned from
      Penicillium freii F63 and overexpressed in Pichia pastoris. man5F63 contained an
      open reading frame of 1260 bp that encoded a polypeptide of 419 amino acids
      including a putative 18-residue signal peptide. The recombinant enzyme (rMan5F63)
      was secreted into the culture supernatant to near electrophoretic homogeneity
      with a high yield (1.1 gl(-1) in flask). Its apparent molecular weight was
      approximately 72.0 kDa, 29.0 kDa higher than the theoretical molecular mass.
      rMan5F63 was optimal at pH 4.5 and 60  degrees C and exhibited good stability
      over a broad pH range from acidic to alkaline (>85.0% activity at pH 4.0-9.0,
      >70.0% activity at pH 10.0 and 43.7% even at pH 12.0). The activity of rMan5F63
      was significantly enhanced in the presence of Co(2+), Cu(2+), Mn(2+) and beta
      mercaptoethanol and was strongly inhibited by Hg(2+) and SDS. The specific
      activity, K(m) and V(max) values were 47.5 U mg(-1), 7.8 mg ml(-1) and 70.4 MUmol
      min(-1)mg(-1), respectively, for locust bean gum, and 40.3 U mg(-1), 2.3 mg ml(
      1) and 61.7 MUmol min(-1)mg(-1), respectively, for konjac flour. All these
      favorable enzymatic properties make it cost-effective to commercialization and
      valuable in various industries.

PMID- 22382014
TI  - Derepression of carbon catabolite repression in an extractive liquid-surface
      immobilization (Ext-LSI) system.
AB  - An extractive liquid-surface immobilization (Ext-LSI) system with a fungal mat
      formed on the surface of a liquid medium effectively enabled derepression of
      carbon catabolite repression. In this system, a fungicidal secondary metabolite 6
      pentyl-alpha-pyrone was efficiently produced by Trichoderma atroviride AG2755
      5NM398 despite the addition of 25% glucose or fructose.

PMID- 22382015
TI  - Large-scale genome reorganization in Saccharomyces cerevisiae through
      combinatorial loss of mini-chromosomes.
AB  - A highly efficient technique, termed PCR-mediated chromosome splitting (PCS), was
      used to create cells containing a variety of genomic constitutions in a haploid
      strain of Saccharomyces cerevisiae. Using PCS, we constructed two haploid
      strains, ZN92 and SH6484, that carry multiple mini-chromosomes. In strain ZN92,
      chromosomes IV and XI were split into 16 derivative chromosomes, seven of which
      had no known essential genes. Strain SH6484 was constructed to have 14 mini
      chromosomes carrying only non-essential genes by splitting chromosomes I, II,
      III, VIII, XI, XIII, XIV, XV, and XVI. Both strains were cultured under defined
      nutrient conditions and analyzed for combinatorial loss of mini-chromosomes.
      During culture, cells with various combinations of mini-chromosomes arose,
      indicating that genomic reorganization could be achieved by splitting chromosomes
      to generate mini-chromosomes followed by their combinatorial loss. We found that
      although non-essential mini-chromosomes were lost in various combinations in
      ZN92, one mini-chromosome (18kb) that harbored 12 genes was not lost. This
      finding suggests that the loss of some combination of these 12 non-essential
      genes might result in synthetic lethality. We also found examples of genome-wide
      amplifications induced by mini-chromosome loss. In SH6484, the mitochondrial
      genome, as well as the copy number of genomic regions not contained in the mini
      chromosomes, was specifically amplified. We conclude that PCS allows for genomic
      reorganization, in terms of both combinations of mini-chromosomes and gene
      dosage, and we suggest that PCS could be useful for the efficient production of
      desired compounds by generating yeast strains with optimized genomic
      constitutions.

PMID- 22382016
TI  - Double knockout of beta-lactamase and cephalosporin acetyl esterase genes from
      Escherichia coli reduces cephalosporin C decomposition.
AB  - The phenomenon of CPC decomposition occurs in Escherichia coli JM105/pMKC-sCPCacy
      during the one-step enzymatic conversion of cephalosporin C (CPC) into 7
      aminocephalosporanic acid (7-ACA) by CPC acylase (sCPCAcy) for synthesis of
      cephalosporin antibiotics. E. coli JM105/pMKC-sCPCacy can constitutively produce
      sCPCacy as a fusion protein with maltose binding protein (MBP). Control
      experiments verified that the cell lysis solution from the host E. coli JM105
      resulted in CPC decomposition by approximately 15%. Two miscellaneous enzymes,
      beta-lactamase (AmpC) and cephalosporin acetyl esterase (Aes), are believed to
      play a major role in the degradation of CPC. Using the Red recombination system,
      the genes ampC, aes or both ampC and aes were knocked out from the chromosome of
      E. coli JM105 to generate the engineers: E. coli JM105(DeltaampC), E. coli
      JM105(Deltaaes) and E. coli JM105(DeltaampC, Deltaaes). The CPC decomposition was
      reduced to 12.2% in E. coli JM105(Deltaaes), 1.3% in E. coli JM105(DeltaampC),
      and even undetectable in ampC-aes double knockout cells of E. coli
      JM105(DeltaampC, Deltaaes). When catalyzed by crude MBP-sCPCAcy isolated from E.
      coli JM105(DeltaampC, Deltaaes)/pMKC-sCPCacy (3377U.l(-1)), the CPC utilization
      efficiency increased to 98.4% from the original 88.7%. Similar results were
      obtained for the ampC-aes double knockout host derived from E. coli JM109(DE3)
      and the CPC utilization efficiency enhanced to 99.3% in the catalysis of crude
      sCPCAcy harvested from E. coli JM109(DE3, DeltaampC, Deltaaes)/pET28-sCPCacy.

PMID- 22382017
TI  - Direct detection of tetrahydrobiopterin (BH4) and dopamine in rat brain using
      liquid chromatography coupled electrospray tandem mass spectrometry.
AB  - A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method was developed for the quantification of tetrahydrobiopterin (BH4) and
      dopamine in rat brain using epsilon-acetamidocaproic acid (AACA) as an internal
      standard. Proteins in the samples were precipitated with acetonitrile and then
      the supernatants were separated by a Sepax Polar-Imidazole (2.1 * 100 mm, i.d., 3
      MUm) column using a mixture of 10mM ammonium formate in acetonitrile/water
      (75:25, v/v) as the mobile phase at a flow rate of 300 MUl/min. Quantification
      was performed on a triple quadrupole mass spectrometer employing electrospray
      ionization with the operating conditions as multiple reaction monitoring (MRM)
      and positive ion mode from m/z 242.1 -> 166.0 for BH4, m/z 154.1 -> 90.0 for
      dopamine and m/z 174.1 -> 114.0 for AACA (IS). The total chromatographic run time
      was for 5.5 min. The method was validated for the analysis of samples: the limit
      of detection was 10 ng/g. The calibration curve was linear between 10-2000 ng/g
      for BH4 (r(2)=0.995) and 10-5000 ng/g for dopamine (r(2)=0.997) in the rat brain.
      Thus, good correlated LC-ESI/MS/MS results were obtained and found to be a
      powerful tool for the quantitative analysis of BH4 and dopamine in the rat brain.

PMID- 22382018
TI  - Using peripheral blood circulating DNAs to detect CpG global methylation status
      and genetic mutations in patients with myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several
      genetic/epigenetic abnormalities are deeply associated with the pathogenesis of
      MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS
      cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is
      difficult to perform repeatedly to obtain serial samples because of pain and
      safety concerns. Here, we report that circulating cell-free DNAs from plasma and
      serum of patients with MDS can be used to detect genetic/epigenetic
      abnormalities. The plasma DNA concentration was found to be relatively high in
      patients with higher blast cell counts in BM, and accumulation of DNA fragments
      from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB)
      samples from patients treated with hypomethylating agents, global methylation
      analysis using bisulfite pyrosequencing was performed at the specific CpG sites
      of the LINE-1 promoter. The results confirmed a decrease of the methylation
      percentage after treatment with azacitidine (days 3-9) using DNAs from plasma,
      serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid
      change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2
      gene mutation in DNAs from plasma, serum, and BM cells was quantitated by
      pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum
      DNA showed almost equivalent level with that in the CD34+/38- stem cell
      population in BM. These data suggest that genetic/epigenetic analyses using PB
      circulating DNA can be a safer and painless alternative to using BM cells.

PMID- 22382019
TI  - Smad3 and Snail show circadian expression in human gingival fibroblasts, human
      mesenchymal stem cell, and in mouse liver.
AB  - Smads are intracellular signaling mediators. Complexes of Smad2 and Smad3 with
      Smad4 transmit transforming growth factor-beta (TGF-beta) receptor-induced
      signaling. Snail plays important roles in mesoderm formation, gastrulation,
      neural crest development, and epithelial mesenchymal transition. However, it
      remains unknown whether Smad3 and Snail expression is circadian rhythm-dependent.
      Here, we showed for the first time that Smad3 and Snail show circadian expression
      in human gingival fibroblasts (HGF-1) and human mesenchymal stem cells (MSC)
      after serum shock. They also showed circadian expression in the mouse liver. We
      confirmed that BMAL1/2, DEC1/2, VEGF, and PER1/2/3 also show circadian expression
      in both HGF-1 and MSC. The mRNA peaks and phases in circadian expression of these
      genes differed between HGF-1 and MSC. In a luciferase assay, Smad3 promoter
      activity was upregulated by CLOCK/BMAL1. These findings suggest that Smad3 and
      Snail have circadian rhythm in vitro and vivo, and that circadian expression of
      Smad3 depends on CLOCK/BMAL1.

PMID- 22382020
TI  - Preparation of amyloid-like fibrils containing magnetic iron oxide nanoparticles:
      effect of protein aggregation on proton relaxivity.
AB  - A method to prepare amyloid-like fibrils functionalized with magnetic
      nanoparticles has been developed. The amyloid-like fibrils are prepared in a two
      step procedure, where insulin and magnetic nanoparticles are mixed simply by
      grinding in the solid state, resulting in a water soluble hybrid material. When
      the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid
      material self assembles to form amyloid-like fibrils incorporating the magnetic
      nanoparticles. This results in magnetically labeled amyloid-like fibrils which
      has been characterized by Transmission Electron Microscopy (TEM) and electron
      tomography. The influence of the aggregation process on proton relaxivity is
      investigated. The prepared materials have potential uses in a range of bio
      imaging applications.

PMID- 22382021
TI  - Multiple targeting motifs direct NRAMP1 into lysosomes.
AB  - Natural resistance-associated macrophage protein 1 (NRAMP1) containing 548 amino
      acids (AA) and 12 transmembrane domains (TMDs) is localized in membranes of
      lysosomes. Our study aimed to investigate the targeting motifs of NRAMP1 by
      expressing GFP-tagged full-length and truncated NRAMP1 proteins and overlapping
      with the lysosomal marker Lamp1-RFP in Chinese hamster ovary (CHO) cells. The
      NH(2)-terminal amino acids 73-140 region including TMD2 was essential for NRAMP1
      lysosomal targeting. The AA.263-334 region containing the tyrosine-based motif
      (327)YAPI(330) targeted NRAMP1 into lysosomes. Additionally, two internal signal
      peptides AA.451-483 and AA.489-522 were identified as lysosomal targeting motifs.
      Taken together, NRAMP1 consists of multiple targeting motifs for trafficking into
      lysosomes.

PMID- 22382022
TI  - The ASB2beta Ubiquitin-interacting motif is involved in its monoubiquitination.
AB  - ASB2 proteins are E3 ubiquitin (Ub) ligases that ubiquitinate filamins. There are
      two ASB2 splice variants, ASB2alpha and ASB2beta. ASB2beta has a ubiquitin
      binding motif (UIM) at the N-terminal region but ASB2alpha does not. Here, we
      provide the first evidence that ASB2beta but not ASB2alpha is monoubiquitinated
      and that this monoubiquitination involves the UIM. Myc-tagged ASB2beta and
      hemagglutinin (HA)-tagged Ub were co-expressed in HEK293 cells using the pCMV
      expression vector. Immunoprecipitation with an anti-Myc antibody followed by
      immunoblotting with anti-Myc and anti-HA antibodies showed an additional ASB2beta
      protein band that had both a Myc and a HA tag. The molecular weight of this
      protein was larger than that of ASB2beta, and the difference in molecular weight
      between these two proteins corresponded to the molecular weight of monoubiquitin,
      strongly implying that monoubiquitinated ASB2beta is produced in cells. ASB2beta
      with mutations in the UIM motif; either Glu.Asp.Glu27-29Ala.Ala.Ala mutations
      (ASB2beta M1) or a Ser38Ala mutation, (ASB2beta M2) were not monoubiquitinated,
      suggesting the importance of the UIM for ASB2beta monoubiquitination.
      Furthermore, an ASB2beta mutant that lacked a SOCS box (ASB2beta DeltaC) and did
      not show E3 Ub ligase activity was monoubiquitinated to the same extent as the
      wild-type ASB2beta. In contrast, an ASB2beta mutant that lacked the UIM
      containing domain (ASB2beta DeltaN) was not monoubiquitinated. These results
      suggest that ASB2beta but not ASB2alpha might be monoubiquitinated and that the
      ASB2beta UIM motif, but not its E3 Ub ligase activity, plays a pivotal role in
      this monoubiquitination.

PMID- 22382023
TI  - Molecular analysis of the TMPRSS3 gene in Moroccan families with non-syndromic
      hearing loss.
AB  - Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common
      type of inherited hearing impairment, accounting for approximately 80% of
      inherited prelingual hearing impairment. Hearing loss is noted to be both
      phenotypically and genetically heterogeneous. Mutations in the TMPRSS3 gene,
      which encodes a transmembrane serine protease, are known to cause autosomal
      recessive non-syndromic hearing impairment DFNB8/10. In order to elucidate if the
      TMPRSS3 gene is responsible for ARNSHI in 80 Moroccan families with non-syndromic
      hearing impairment, the gene was sequenced using DNA samples from these families.
      Nineteen TMPRSS3 variants were found, nine are located in the exons among which
      six are missense and three are synonymous. The 10 remaining variations are
      located in non-coding regions. Missense variants analysis show that they do not
      have a significant pathogenic effect on protein while pathogenicity of some
      variant remains under discussion. Thus we show that the TMPRSS3 gene is not a
      major contributor to non-syndromic deafness in the Moroccan population.

PMID- 22382024
TI  - Silencing glypican-3 expression induces apoptosis in human hepatocellular
      carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common internal malignant
      tumors. Glypican-3 (GPC3) is involved in the biological and molecular events in
      the tumorigenesis of HCC. We used RNA interference to evaluate the molecular
      effects of GPC3 suppression at the translational level and demonstrated for the
      first time that GPC3 silencing results in a significant elevation of the Bax/Bcl
      2 ratio, the release of cytochrome c from mitochondria and the activation of
      caspase-3. The results suggest that GPC3 regulates cell proliferation by
      enhancing the resistance to apoptosis through the dysfunction of the Bax/Bcl
      2/cytochrome c/caspase-3 signaling pathway and therefore plays a critical role in
      the tumorigenesis of HCC. Thus, the knockdown of GPC3 should be further
      investigated as an attractive novel approach for the targeted gene therapy of
      HCC.

PMID- 22382025
TI  - A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy.
AB  - A large four-generation Chinese family with autosomal dominant optic atrophy
      (ADOA) was investigated in the present study. Eight of the family members were
      affected in this pedigree. The affected family members exhibited early-onset and
      progressive visual impairment, resulting in mild to profound loss of visual
      acuity. The average age-at-onset was 15.9years. A new heterozygous mutation
      c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene.
      This mutation resulted in a proline to alanine substitution at codon 400, which
      was located in an evolutionarily conserved region. This missense mutation in the
      GTPase domain was supposed to result in a loss of function for the encoded
      protein and act through a dominant negative effect. No other mutations associated
      with optic atrophy were found in our present study. The c.C1198G heterozygous
      mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree
      with ADOA. Furthermore, additional nuclear modifier genes, environmental factors,
      and psychological factors may also contribute to the phenotypic variability of
      ADOA in this pedigree.

PMID- 22382026
TI  - Identification of a novel tetrapeptide structure of the Mycobacterium avium
      glycopeptidolipid that functions as a specific target for the host antibody
      response.
AB  - Mycobacterium avium complex (MAC) is a group of non-tuberculous mycobacteria that
      cause tuberculosis-like diseases in humans. Unlike Mycobacterium tuberculosis,
      MAC expresses high levels of glycopeptidolipids (GPLs) containing a well-defined
      tetrapeptide-amino alcohol core, composed of D-phenylalanine, D-allo-threonine, D
      alanine, and L-alaninol, that is modified with a fatty acid and sugar residues.
      Surprisingly, however, a careful scrutiny of the mass spectrum of MAC GPLs
      revealed the presence of ions that could not readily accountable for the known
      GPL structure. The magnitude of the ions was increased prominently when GPLs were
      isolated from the valine-supplemented culture, and the ions representing the
      authentic GPL species were diminished, suggesting the possibility that the basic
      structure of the peptide backbone might be altered in response to the exogenously
      added valine. Indeed, further mass spectrometry (MS)/MS and gas chromatography-MS
      analysis indicated a substitution of D-valine for the N-terminal D-phenylalanine
      of the tetrapeptide core, and the presence of D-valine and the absence of D
      phenylalanine was confirmed by high-performance liquid chromatography, using the
      derivatized amino acid residues that were released from the tetrapeptide.
      Finally, specific antibodies to the purified valine-containing GPL species were
      detected in the serum of a MAC-infected guinea pig. Therefore, these results
      identify a new molecular species of MAC GPLs with immunogenic potential.

PMID- 22382027
TI  - Calcium-calmodulin signaling induced by epithelial cell differentiation
      upregulates BRAK/CXCL14 expression via the binding of SP1 to the BRAK promoter
      region.
AB  - The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but
      is not expressed or is expressed at negligible levels in head and neck squamous
      cell carcinoma. Malignant cells are known to be dedifferentiated compared with
      normal epithelial cells, suggesting a role for differentiation cues in the
      expression of BRAK. Thus, we examined the relationship between BRAK expression
      and stages of differentiation level in epithelial cells. Immunohistochemical
      analysis showed that BRAK protein was expressed in cells above the spinous cell
      layer in normal epithelia. In HSC-3 cells in culture, expression of BRAK mRNA was
      significantly upregulated by cell contact in a cell density-dependent manner, and
      mRNA expression of cell differentiation markers such as involucrin, cystatin-A,
      TGM1, TGM3, and TGM5 was concomitantly augmented. Furthermore, the upregulation
      of BRAK induced by cell contact was suppressed by chlorpromazine, a specific
      inhibitor of calmodulin. We previously reported that GC boxes and a TATA-like
      sequence in the BRAK promoter region are associated with the expression of BRAK.
      Using a promoter assay and ChIP, we demonstrated that binding of the stimulating
      protein-1 (SP1) transcription factor to a GC box upstream of the BRAK
      transcription start site was necessary for cell density-dependent upregulation of
      BRAK. These results indicated that upregulation of BRAK was accompanied by
      differentiation of epithelial cells induced by calcium/calmodulin signaling, and
      that SP1 binding to the BRAK promoter region played an important role in this
      signaling.

PMID- 22382028
TI  - Yeast mannan structure necessary for co-aggregation with Lactobacillus plantarum
      ML11-11.
AB  - Lactic acid bacteria (LAB) Lactobacillus plantarum ML11-11, an isolate from
      Fukuyama pot vinegar, and yeast Saccharomyces cerevisiae form significant mixed
      species biofilm with direct cell-cell contact. Co-aggregation of L. plantarum
      ML11-11 and S. cerevisiae cells, mediated by the interaction between surface
      protein(s) on L. plantarum ML11-11 cells and surface mannan of S. cerevisiae
      cells, contributes significantly to mixed-species biofilm formation. In this
      study, co-aggregation activities of yeast mutants that were deleted of genes
      related to mannan biosynthesis were investigated to clarify the mannan structures
      essential for interaction with L. plantarum ML11-11. Among the 12 deletion
      mutants which had various incomplete mannan structures, only the mnn2 mutant lost
      the co-aggregation activity. In the mnn2 mutant, the gene coding the activity of
      attaching first branching mannose residue to mannan main chain is deleted and
      therefore the mnn2 mutant has unbranched mannan. From this result, it is
      clarified that the specific structure, consisted of mannan main chain to which
      are attached side chains containing one or more mannose residues, is critical for
      co-aggregation with L. plantarum ML11-11.

PMID- 22382029
TI  - Requirement of protein l-isoaspartyl O-methyltransferase for transcriptional
      activation of trefoil factor 1 (TFF1) gene by estrogen receptor alpha.
AB  - Lysine- and arginine-specific methyltransferases have been shown to act as either
      direct or secondary transcriptional co-activator of the estrogen receptor
      (ERalpha). However, little is known about the role of protein l-isoaspartyl O
      methyltransferase (PIMT) on transcriptional regulation. Here, we show that PIMT
      acts as a co-activator for ERalpha-mediated transcription. Activation of the
      estrogen response element (ERE) promoter by beta-estradiol (E(2)) was suppressed
      by knockdown of PIMT, and enhanced by overexpression of wild-type PIMT. However,
      the ERE promoter activity was resistant to E(2) stimulation in cells
      overexpressing a catalytically inactive PIMT mutant, G88A. Consistent with these
      results, the expression of the endogenous ERalpha response gene trefoil factor 1
      (TFF1) by E(2) was completely abrogated by PIMT depletion and decreased to
      approximately 50% when PIMT mutant G88A was expressed. In addition, over
      expression of PIMT significantly increased the levels of TFF1 mRNA in the
      presence or absence of E(2). Interestingly, PIMT interacted with ERalpha and was
      distributed to the cytosol and the nucleus. The chromatin immunoprecipitation
      analysis revealed that PIMT was recruited to the promoter of TFF1 gene together
      with ERalpha in an E(2)-dependent manner, which was accompanied by uploading of
      RNA polymerase II on the promoter. Taken together, the results suggest that PIMT
      may act as a co-activator in ERalpha-mediated transcription through its
      recruitment to the promoter via interacting with ERalpha.

PMID- 22382030
TI  - CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic
      pathways in VSMC.
AB  - ANRIL is a newly discovered non-coding RNA lying on the strongest genetic
      susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21
      region. Genome-wide association studies have been linking polymorphisms in this
      locus with CVD and several other major diseases such as diabetes and cancer. The
      role of this non-coding RNA in atherosclerosis progression is still poorly
      understood. In this study, we investigated the implication of ANRIL in the
      modulation of gene sets directly involved in atherosclerosis. We designed and
      tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of
      the transcript and successfully knocked down expression of ANRIL in human aortic
      vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array
      to profile gene expression changes caused by ANRIL knock down. Notably, the genes
      affected by each of the siRNAs were different, suggesting that different splicing
      variants of ANRIL might have distinct roles in cell physiology. Our results
      suggest that ANRIL splicing variants play a role in coordinating tissue
      remodeling, by modulating the expression of genes involved in cell proliferation,
      apoptosis, extra-cellular matrix remodeling and inflammatory response to finally
      impact in the risk of cardiovascular disease and other pathologies.

PMID- 22382031
TI  - Screening of a highly soluble and oxygen-independent blue fluorescent protein
      from metagenome.
AB  - GFP and its derivatives are commonly used as non-invasive in vivo reporters.
      These fluorescent proteins have been employed to analyze expression level,
      localization and movement of proteins, as well as protein interaction. However,
      they cannot be utilized under anaerobic conditions due to the oxygen requirement
      for the maturation of the fluorophore. Thus, other proteins with a different
      mechanism of fluorescence emission are needed. We reported here a blue
      fluorescent protein, named mBFP, that was derived from metagenomic DNA. This
      protein consisting of 248 amino acids was overexpressed (>35% of the total
      protein) in a soluble form in Escherichia coli. mBFP showed a distinct
      fluorescence pattern that was NADPH-dependent and could be used to image live
      cells under anaerobic conditions. Thus, mBFP holds great promise for use as a
      reporter in a broad range of applications.

PMID- 22382032
TI  - Wandering hemi-spleen: Laparoscopic management of wandering spleen in a case of
      polysplenia.
AB  - INTRODUCTION: Several congenital anomalies of the spleen have been reported. The
      polysplenia is a rare anomaly in which the normal spleen is replaced with two or
      more smaller spleens. The wandering spleen is another anomaly resulting from the
      laxity of the splenic ligaments. The concomitance of both anomalies is very rare.
      PRESENTATION OF A CASE: A 22-year old female patient presented with intermittent
      left hypochondrial pain for more than a year. After a thorough examination of the
      patient, she only had bilateral accessory nipples. Routine laboratory
      investigations were all normal. An abdominal ultrasound U/S scan was unremarkable
      except for a ptotic spleen. with a large splenule 5cm*3cm located near the fundus
      of the stomach. These findings were confirmed by a CT scan. A decision for a
      surgical intervention was then made, and the laparoscopic approach was chosen
      which revealed the condition. Laparoscopic removal of the wandering part was
      executed. The patient discharged on the first post-operative day. DISCUSSION: The
      decision making in cases of wandering spleen is not always the same. The
      association of a wandering spleen with polysplenia is an asset to the surgical
      decision, along with the age of the patient. CONCLUSION: The laparoscopic
      approach is an important tool in the diagnosis and management of wandering
      spleen. The diagnosis of polysplenic anomaly could provide a guidance for the
      surgical strategy in patients with wandering spleen.

PMID- 22382033
TI  - Phytobezoar in Meckel's diverticulum: A rare cause of small bowel obstruction.
AB  - INTRODUCTION: Meckel's diverticulum (MD) is the prevailing anomaly of the
      gastrointestinal tract, found in about 2% of the population; it rarely gives rise
      to symptoms and its discovery is usually accidental. Phytobezoar is a concretion
      of poorly digested fruit and vegetable fibres that is found in the alimentary
      tract and rarely can be the cause of small intestinal obstruction. Herein we
      report a rare case of intestinal obstruction due to phytobezoar formation into a
      MD. PRESENTATION OF CASE: A 50 year-old patient, was admitted to author's
      institution with an history of abdominal pain, nausea and multiples episodes of
      vomiting. Plain X-ray showed dilated small-bowel loops. Computed tomography (CT)
      revealed jejunal loops with air-fluid levels. The patient underwent explorative
      laparotomy where we found a giant Meckel's diverticulum, filled by a phytobezoar
      that caused small bowel compression. We performed a segmental ileal, resection,
      containing the MD. The histological exam confirmed Meckel's diverticulum.
      DISCUSSION: Bowel obstruction due to a phytobezoar in a Meckel's diverticulum is
      rare: only 7 cases have been reported in literature. MD complications are rare
      and phytobezoar is one of them with only few cases described in literature.
      CONCLUSION: The conventional x rays studies were inconclusive whereas abdominal
      contrast enhanced CT led to a definitive diagnosis. Explorative laparotomy or
      laparoscopy is mandatory in these cases.

PMID- 22382034
TI  - Glenohumeral tuberculous arthritis complicated with beta haemolytic
      streptococcus: An extraordinary rare association: A case report.
AB  - INTRODUCTION: Septic arthritis of the glenohumeral joint is a rare entity and its
      diagnosis is difficult with a superadded infection in the presence of underlying
      tuberculosis. We report the first case of group B beta haemolytic streptococcal
      glenohumeral arthritis with underlying tuberculosis. CASE PRESENTATION: A 40 year
      old lady previously diagnosed to have poliomyelitis, rheumatoid arthritis,
      hepatitis C, and diabetes mellitus for the last 10 years, presented to the
      emergency room with diabetic ketoacidosis. Two weeks prior to presentation she
      developed fever along with pain and swelling in left shoulder with uncontrolled
      blood sugars. Local examination of the shoulder revealed global swelling with
      significant restricted range of motion. MRI showed a large multiloculated
      collection around the left shoulder joint extending into the axilla, and proximal
      arm. Urgent arthrotomy performed and about 120ml thick pus was drained. The
      patient was started on clindamicin and antituberculous chemotherapy and her
      symptoms dramatically improved. DISCUSSION: Bone and joint involvement accounts
      for approximately 2% of all reported cases of tuberculosis (TB), and it accounts
      for approximately 10% of the extra pulmonary cases of TB. Tuberculosis of the
      shoulder joint constitutes 1-10.5% of skeletal tuberculosis. Classical symptoms
      of fever, night sweats, and weight loss may be absent, and a concurrent pulmonary
      focus may not be evident in most cases. CONCLUSION: Despite acute presentation of
      septic arthritis, in areas endemic for tuberculosis and particularly in an
      immunocompromised patient, workup for tuberculosis should be part of the routine
      evaluation.

PMID- 22382035
TI  - Successful pleurodesis for refractory chylothorax due to chronic lymphocytic
      leukemia.
AB  - INTRODUCTION: Chylothorax is a very rare complication of chronic lymphocytic
      leukemia. PRESENTATION OF CASE: We describe the case of an 83-year old woman with
      chronic lymphocytic leukemia, complicated by recurrent chylothorax and ultimately
      treated by pleurodesis with bleomycin. DISCUSSION: There are several options for
      management of patients presenting with chylothorax due to chronic lymphocytic
      leukemia. CONCLUSION: Pleurodesis is a reasonable and effective treatment
      modality for patients with refractory chylothorax.

PMID- 22382036
TI  - Metabolic actions of hypothalamic SIRT1.
AB  - The hypothalamus is a small structure located in the ventral diencephalon.
      Hypothalamic neurons sense changes in circulating metabolic cues (e.g. leptin,
      insulin, glucose), and coordinate responses aimed at maintaining normal body
      weight and glucose homeostasis. Recent findings indicate that a nicotinamide
      adenine dinucleotide (NAD(+))-dependent protein deacetylase (namely SIRT1)
      expressed by hypothalamic neurons is crucial for mounting responses against diet
      induced obesity and type 2 diabetes mellitus (T2DM). Here, the repercussions of
      these findings will be discussed and particular emphasis will be given to the
      potential exploitation of hypothalamic SIRT1 as a target for the treatment of the
      rapidly-spreading metabolic disorders of obesity and T2DM. The possible roles of
      hypothalamic SIRT1 in regulating metabolic ageing processes will also be
      addressed.

PMID- 22382037
TI  - The influence of user characteristics and a periodic email prompt on exposure to
      an internet-delivered computer-tailored lifestyle program.
AB  - BACKGROUND: The Internet is a promising medium in the field of health promotion
      for offering tailored and targeted lifestyle interventions applying computer
      tailored (CT) techniques to the general public. Actual exposure to CT
      interventions is not living up to its high expectations, as only a (limited)
      proportion of the target group is actually using these programs. OBJECTIVE: To
      investigate exposure to an Internet-delivered, CT lifestyle intervention,
      targeting physical activity, fruit and vegetable intake, smoking behavior, and
      alcohol intake, we focused on three processes: first use, prolonged use, and
      sustained use. The first objectives were to identify user characteristics that
      predict initiation of an online CT lifestyle program (first use) and completion
      of this program (prolonged use). Furthermore, we studied the effect of using a
      proactive strategy, consisting of periodic email prompts, on program revisits
      (sustained use). METHODS: The research population for this study consisted of
      Dutch adults participating in the Adult Health Monitor, offered by the regional
      public health services. We used a randomized controlled trial design to assess
      predictors of first use, prolonged use, and sustained use. Demographics and
      behavioral characteristics, as well as the strategy used for revisiting, were
      included as predictors in the model. RESULTS: A total of 9169 participants
      indicated their interest in the new program and 5168 actually logged in to the
      program. Participants significantly more likely to initiate one of the CT modules
      were male, older, and employed, and had a lower income, higher body mass index,
      and relatively unhealthy lifestyle. Participants significantly more likely to
      complete one of the CT modules were older and had a higher income and a
      relatively healthier lifestyle. Finally, using a proactive strategy influenced
      sustained use, with people from the prompting condition being more likely to
      revisit the program (odds ratio 28.92, 95% confidence interval 10.65-78.52; P <
      .001). CONCLUSIONS: Older, male, and employed participants, and those with a
      lower income, higher body mass index, and a relatively unhealthy lifestyle were
      more likely to initiate a CT module. Module completers predominantly had a higher
      income and age. The current program therefore succeeded in reaching those people
      who benefit most from online lifestyle interventions. However, these people
      tended to disengage from the program. This underlines the importance of
      additional research into program adjustments and strategies that can be used to
      stimulate prolonged program use. Furthermore, sending periodic email prompts
      significantly increased revisits to the program. Though promising, this effect
      was modest and needs to be further examined, in order to maximize the potential
      of periodic email prompting. TRIAL REGISTRATION: Nederlands Trial Register (NTR:
      1786) and Medical Ethics Committee of Maastricht University and the University
      Hospital Maastricht (NL2723506809/MEC0903016);
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1786 (Archived by
      WebCite at http://www.webcitation.org/65hBXA6V7).

PMID- 22382039
TI  - Intermittent maximal exercise improves attentional performance only in physically
      active students.
AB  - BACKGROUND AND AIMS: Regular physical activity participation seems to be linked
      to brain metabolism and to be one factor responsible for different effects of
      high intensity exercise on cognition. Due to this, we investigated the effect of
      an intermittent maximal exercise intervention on a neuropsychological test
      requiring sustained and selective attention in a group of low and high physically
      active subjects. METHOD: Forty six healthy students (age: M = 23.11, SD = 2.60
      years) performed in a cross-over design an intermittent incremental exercise
      until they reached their maximal heart rate (HR Max; intervention condition) or
      rested for the same duration (control condition) followed by the administration
      of the d2-test. RESULTS: A significant interaction between physical activity
      participation level and exercise effect on cognitive performance emerged, with
      only the more physically active participants improving the performance in the
      cognitive test after the intervention. CONCLUSION: These data extend the current
      knowledge base by showing that a higher participation rate in physical activity
      may lead to neurobiological adaptations that facilitate selected cognitive
      processes (i.e., attention) after high exercise intensities.

PMID- 22382038
TI  - Biosynthesis of pyrrolopyrimidines.
AB  - Pyrrolopyrimidine containing compounds, also known as 7-deazapurines, are a
      collection of purine-based metabolites that have been isolated from a variety of
      biological sources and have diverse functions which range from secondary
      metabolism to RNA modification. To date, nearly 35 compounds with the common 7
      deazapurine core structure have been described. This article will illustrate the
      structural diversity of these compounds and review the current state of knowledge
      on the biosynthetic pathways that give rise to them.

PMID- 22382040
TI  - Molecular analysis of the UROD gene in 17 Argentinean patients with familial
      porphyria cutanea tarda: characterization of four novel mutations.
AB  - Porphyria cutanea tarda (PCT) is caused by decreased activity of uroporphyrinogen
      decarboxylase (UROD) in the liver. The disease usually occurs in adulthood and is
      characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility
      and hypertrichosis, due to the accumulation of porphyrins produced by oxidation
      of uroporphyrinogen and other highly carboxylated porphyrinogens overproduced as
      a result of the enzyme deficiency. PCT is generally sporadic, but about 20-30% of
      patients have familial-PCT (F-PCT) which is associated with heterozygosity of
      mutations in the UROD gene. In the present study we have found the molecular
      defect in seventeen unrelated Argentinean patients with F-PCT, identifying a
      total of eleven UROD gene mutations: four novel and seven previously described.
      The novel mutations were: a guanine insertion at the 5' splice junction of intron
      2, a three nucleotide deletion causing the lost of valine 90, a deletion of 22 bp
      in exon 6 and a deletion of part of the polyadenylation signal. Prokaryotic
      expression studies showed that the novel amino acid deletion resulted in an
      inactive protein. Mutations c.10insA and p.M165R, previously found in Argentinean
      patients, were recurrent in this study; they are the most frequent in Argentina
      accounting for 40% of the mutant alleles characterized to date.

PMID- 22382041
TI  - Application of the ecohealth model to translate knowledge into action in the
      health sciences.

PMID- 22382042
TI  - Experimental investigation of the quality characteristics of agricultural plastic
      wastes regarding their recycling and energy recovery potential.
AB  - A holistic environmentally sound waste management scheme that transforms
      agricultural plastic waste (APW) streams into labelled guaranteed quality
      commodities freely traded in open market has been developed by the European
      research project LabelAgriWaste. The APW quality is defined by the APW material
      requirements, translated to technical specifications, for recycling or energy
      recovery. The present work investigates the characteristics of the APW quality
      and the key factors affecting it from the introduction of the virgin product to
      the market to the APW stream reaching the disposer. Samples of APW from different
      countries were traced from their application to the field through their storage
      phase and transportation to the final destination. The test results showed that
      the majority of APW retained their mechanical properties after their use
      preserving a "very good quality" for recycling in terms of degradation. The
      degree of soil contamination concerning the APW recycling and energy recovery
      potential fluctuates depending on the agricultural plastic category and
      application. The chlorine and heavy metal content of the tested APW materials was
      much lower than the maximum acceptable limits for their potential use in cement
      industries.

PMID- 22382043
TI  - Solid waste facilities location using of analytical network process and data
      envelopment analysis approaches.
AB  - Selection of the appropriate site for solid waste facilities is a complex problem
      and requires an extensive evaluation process, because it is very difficult to
      develop a selection criterion that can precisely describe the preference of one
      location over another. Therefore selection of these sites can be viewed as a
      multiple criteria decision-making or multiple attributes decision-making problem.
      For this purpose, we propose a technique that can effectively take managerial
      preferences and subjective data into consideration, along with quantitative
      factors. The tool proposed here relies on the use of the analytical network
      process (ANP) and to help integrate managerial evaluations into a more
      quantitatively based decision tool, data envelopment analysis (DEA) is applied.
      In this paper, a location selection procedure is presented to construct an
      undesirable facility applying ANP and DEA approaches in two stages. In the first
      stage ANP approach is used, results of this stage are inputs for the second
      stage. In this stage, DEA is applied to select the best location. Finally, to
      illustrate the proposed framework, at "Results and discussion" section, a total
      of four undesirable facility locations are evaluated.

PMID- 22382044
TI  - Electrical transport properties of single wall carbon nanotube/polyurethane
      composite based field effect transistors fabricated by UV-assisted direct-writing
      technology.
AB  - We report on the fabrication and transport properties of single-walled carbon
      nanotube (SWCNT)/polyurethane (PU) nanocomposite microfiber-based field effect
      transistors (FETs). UV-assisted direct-writing technology was used, and
      microfibers consisting of cylindrical micro-rods, having different diameters and
      various SWCNT loads, were fabricated directly onto SiO2/Si substrates in a FET
      scheme. The room temperature dc electrical conductivities of these microfibers
      were shown to increase with respect to the SWCNT concentrations in the
      nanocomposite, and were about ten orders of magnitude higher than that of the
      pure polyurethane, when the SWCNT load ranged from 0.1 to 2.5 wt% only. Our
      results show that for SWCNT loads <= 1.5 wt%, all the microfibers behave as a FET
      with p-type transport. The resulting FET exhibited excellent performance, with an
      I(on)/I(off) ratio of 105 and a maximum on-state current (I(on)) exceeding 70 uA.
      Correlations between the FET performance, SWCNTs concentration, and the
      microfiber diameters are also discussed.

PMID- 22382045
TI  - Reductions in convictions for violent crime during opioid maintenance treatment:
      a longitudinal national cohort study.
AB  - BACKGROUND: Although opioid maintenance treatment (OMT) has been found to reduce
      crime, less is known about its associations with violent crime. This study
      investigates changes in violent crime convictions prior to, during, and after
      OMT, and examines the relationship between violent crime convictions prior to OMT
      with the risk of violent and non-violent crime convictions during treatment.
      METHODS: The cohort comprised all who started OMT (n=3221) in Norway between 1997
      and 2003. Treatment data were cross linked with the national Crime Registry.
      Convictions for violent crime 3 years prior to, during, and after treatment were
      studied. RESULTS: Violent crime rates were significantly reduced during OMT
      compared with before treatment, for both men and women. The rate of convictions
      for violent crime during OMT was halved amongst those who remained in treatment.
      The reduction was less pronounced for those who left treatment: for this group,
      the rate of violent convictions after OMT was higher than before treatment. The
      risk of convictions for violent and non-violent crime during OMT was highest for
      those with violent convictions prior to treatment. CONCLUSIONS: Violent crime is
      reduced during OMT. Screening for violent behaviour and violence risk assessment
      should be implemented in the treatment system.

PMID- 22382046
TI  - What Oregon's parity law can tell us about the federal Mental Health Parity and
      Addiction Equity Act and spending on substance abuse treatment services.
AB  - BACKGROUND: The Paul Wellstone and Pete Domenici Mental Health Parity and
      Addiction Equity Act of 2008 (MHPAEA) requires commercial group health plans
      offering coverage for mental health and substance abuse services to offer those
      services at a level that is no more restrictive than for medical-surgical
      services. The MHPAEA is notable in restricting the extent to which health plans
      can use managed care tools on the behavioral health benefit. The only precedent
      for this approach is Oregon's 2007 state parity law. This study aims to provide
      evidence on the effect of comprehensive parity on utilization and expenditures
      for substance abuse treatment services. METHODS: A difference-in-difference
      analysis compared individuals in five Oregon commercial plans (n=103,820) from
      2005 to 2008 to comparison groups exempt from parity in Oregon (n=19,633) and
      Washington (n=39,447). The primary outcome measures were annual use and total
      expenditures. RESULTS: Spending for alcohol treatment services demonstrated
      statistically significant increase in comparison to the Oregon and Washington
      comparison groups. Spending on other drug abuse treatment services was not
      associated with statistically significant spending increases, and the effect of
      parity on overall spending (alcohol plus other drug abuse treatment services) was
      positive but not statistically significant from zero. CONCLUSIONS: Oregon's
      experience suggests that behavioral health insurance parity that places
      restrictions on how plans manage the benefit may lead to increases in
      expenditures for alcohol treatment services but is unlikely to lead to increases
      in spending for other drug abuse treatment services.

PMID- 22382048
TI  - Development of phonological awareness in English-Mandarin bilinguals: a
      comparison of English-L1 and Mandarin-L1 kindergarten children.
AB  - Phoneme awareness is critical for literacy acquisition in English, but relatively
      little is known about the early development of phonological awareness in ESL
      (English as a second language) bilinguals when their two languages have different
      phonological structures. Using parallel tasks in English and Mandarin, we tracked
      the development of L1 (first language) and L2 (second language) syllable and
      phoneme awareness longitudinally in English-L1 and Mandarin-L1 prereaders (n=70,
      4- and 5-year-olds) across three 6-month intervals. In English, the English-L1
      children's performance was better in phoneme awareness at all three time points,
      but the Mandarin-L1 children's syllable awareness was equivalent to the English
      L1 children's syllable awareness by Time 3. In Mandarin, the English-L1
      children's phoneme awareness, but not their syllable awareness, was also
      significantly better than that of the Mandarin-L1 children at all three time
      points. Cross-lagged correlations revealed that only the English-L1 children
      applied their L1 syllable and phoneme awareness to their L2 (Mandarin) processing
      by Time 2 and that the Mandarin-L1 children seemed to require exposure to English
      (L2) before they developed phoneme awareness in either language. The data provide
      further evidence that phonological awareness is a language-general ability but
      that cross-language application depends on the similarity between the
      phonological structures of a child's L1 and L2. Implications for classroom
      teaching are briefly discussed.

PMID- 22382047
TI  - Application of the Sit-Up Test for orthostatic hypotension in individuals with
      stroke.
AB  - Orthostatic hypotension (OH) is an important consideration for individuals with
      stroke, given the shared occurrence of mobility limitations, fall risk and
      association with adverse cardiovascular outcomes. This study aimed to 1)
      establish the application of a simple bedside test of orthostatic challenge to
      identify OH after stroke, 2) examine differences in characteristics between those
      with and without OH and 3) determine cardiovascular correlates with hemodynamic
      responses. Forty-nine participants (n=29 men, mean +/- SD age 66 +/- 7 years,
      time post-stroke 4.5 +/- 3.1 years) performed an orthostatic challenge (Sit-Up
      Test). Eleven (22%) of the 49 participants presented with OH (n=7, of which 5
      were asymptomatic) or symptoms of cerebral hypoperfusion with position change
      (n=4). Compared to participants without OH, those with OH had higher total:high
      density lipoprotein cholesterol ratios (4.2 +/- 0.9 vs. 3.3 +/- 0.8, P=0.009) and
      triglyceride levels (2.2 +/- 0.8 vs. 1.4 +/- 0.5 mmol/L, P=0.001). Multivariate
      linear regression revealed that high-density lipoprotein cholesterol and
      triglyceride levels explained 20% of the variance of the change in systolic blood
      pressure from the Sit-Up Test (F(2,45)=5.68, P=0.006). In conclusion, we used a
      simple bedside test of orthostatic tolerance to identify that over 20% of
      individuals with stroke presented with OH or symptoms of hypoperfusion. They also
      had more impaired cardiovascular risk profiles relative to those without OH.
      These individuals may be at even higher risk for mobility limitations and falls
      beyond that associated with stroke-related deficits alone.

PMID- 22382049
TI  - Misperceiving facial affect: effects of laterality and individual differences in
      susceptibility to visual hallucinations.
AB  - It has been suggested that certain types of auditory hallucinations may be the by
      product of a perceptual system that has evolved to be oversensitive to threat
      related stimuli. People with schizophrenia and high schizotypes experience visual
      as well as auditory hallucinations, and have deficits in processing facial
      emotions. We sought to determine the relationship between visual hallucination
      proneness and the tendency to misattribute threat and non-threat related emotions
      to neutral faces. Participants completed a questionnaire assessing visual
      hallucination proneness (the Revised Visual Hallucination Scale - RVHS). High
      scoring individuals (N=64) were compared to low scoring individuals (N=72) on a
      novel emotion detection task. The high RVHS group made more false positive errors
      (ascribing emotions to neutral faces) than the low RVHS group, particularly when
      detecting threat-related emotions. All participants made more false positives
      when neutral faces were presented to the right visual field than to the left
      visual field. Our results support continuum models of visual hallucinatory
      experience in which tolerance for false positives is highest for potentially
      threatening emotional stimuli and suggest that lateral asymmetries in face
      processing extend to the misperception of facial emotion.

PMID- 22382050
TI  - Association study of genes regulating opioid system in autism.

PMID- 22382051
TI  - Subjective well-being, hope, and needs of individuals with serious mental
      illness.
AB  - Hope, as a basic resource in human life, may affect individuals' perceptions of
      subjective well-being (SWB). Further, understanding individuals' needs is
      essential to improving their SWB. It is unclear how the impact of hope on SWB may
      be mediated by needs. The current study aimed to examine a mediation model for
      the relation between hope and SWB among individuals with serious mental illness
      (SMI). Face-to-face structured interviews were conducted with 172 individuals
      with SMI. Instruments included the Personal Wellbeing Index, the Hope Scale, and
      the Camberwell Assessment of Needs. Hope and needs were predictive of 40% of the
      variability in SWB, with hope being a stronger predictor. Having no needs was
      positively predictive of SWB, while total number of needs was negatively
      predictive of SWB. Path analyses revealed a strong direct effect of hope on SWB
      and a weaker, though still strong, indirect effect mediated through needs. The
      results underscore the importance of hope in improving SWB and, consequently,
      enhancing the recovery process of individuals with SMI. Therefore, mental health
      services should focus on hope-building.

PMID- 22382052
TI  - A DRD2 and ANKK1 haplotype is associated with nicotine dependence.
AB  - To test the importance of the dopamine D2 receptor (DRD2) region in nicotine
      dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, 
      141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497,
      respectively). The -141delC SNP did not show any association but both the C957T
      and TaqIA SNPs showed association at the allele, genotype, haplotype and combined
      genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to
      be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype
      (P=0.003). Analysis of the combined genotypes of both SNPs revealed that
      individuals who were homozygous for the 957C-allele (CC) and had either one or
      two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine
      dependence compared to all other genotype combinations (P=0.0003) and that these
      genotypes accounted for approximately 13% of the susceptibility to nicotine
      addiction in our population. Our findings suggest that the DRD2 C957T
      polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic
      susceptibility to nicotine dependence.

PMID- 22382053
TI  - Alexithymia is not a stable personality trait in patients with substance use
      disorders.
AB  - The construct of alexithymia as a vulnerability factor for substance use
      disorders (SUD) is under debate, because of conflicting research results
      regarding alexithymia as a state or trait phenomenon. The absolute and relative
      stability of alexithymia were evaluated in a pre-post design as part of a
      randomised controlled trial, controlling for several co-variates. Assessments
      were done with the Toronto Alexithymia Scale (TAS-20) and the Addiction Severity
      Index (EuropASI) at baseline and follow-up of a 3-month trial of inpatient
      Cognitive Behavioural Therapy (CBT) with or without a Shared Decision Making
      intervention for 187 SUD patients. Paired sample t-tests and analyses of variance
      were performed to assess absolute stability, intraclass correlation coefficients
      were calculated for relative stability and multivariate linear regression models
      were used to evaluate the relation between co-variates and change in alexithymia.
      Mean level reduction of total TAS-20 and two subfactors demonstrated no absolute
      stability, but change in alexithymia differed for patients with low, moderate and
      high alexithymia scores. Relative stability of alexithymia was moderate to high
      for the total population, but differed according to low, moderate and high
      alexithymia scores. The EuropASI "psychiatry" domain, covering anxiety and
      depression, was related to alexithymia, but CBT-related variables were not. In
      conclusion, alexithymia is partly a state-dependent phenomenon, but not a stable
      personality trait in this SUD population.

PMID- 22382054
TI  - [Recent advances in natriuretic peptide family genes and cardiovascular
      diseases].
AB  - Natriuretic peptide family consists of several hormones produced by
      cardiomyocyte, including atrial natriuretic peptide (ANP), brain natriuretic
      peptide (BNP) and C-type natriuretic peptide (CNP). They possess similar gene
      structures and protective effects of cardiovascular physiology, such as anti
      hypertrophy, anti-fibrosis, myocardial relaxation and blood pressure regulation.
      The corresponding natriuretic peptide receptor A, B and C mediate multiple
      effects of natriuretic peptides to maintain cardiovascular homeostasis.
      Specially, natriuretic peptide receptor-A preferentially binds ANP and BNP, while
      natriuretic peptide receptor-B is more selective for C-type natriuretic peptides.
      Natriuretic peptide receptor-C(NPR-C), binding all kinds of natriuretic peptides,
      clears natriuretic peptides from the circulation through receptor-mediated
      internalization and degradation. BNP levels were reported to be a good predictor
      of left ventricular dysfunction and decompensated heart failure from a clinical
      standpoint. BNP infusion is an effective treatment for acute heart failure.
      Investigations on natriuretic peptides' single nucleotide polymorphisms and
      biological function suggested that they could be associated with several
      cardiovascular diseases, such as atrial fibrillation, cardiomyopathy, heart
      failure and so on. Transgenic mice with natriuretic peptides and their receptors
      gene deletion display myocardial hypertrophy and fibrosis, which are associated
      with the development of hypertension, cardiomyopathy and heart failure. Certain
      stimuli triggering cardiac hypertrophy and ischemic injuries may be involved in
      regulating gene expression of natriuretic peptides and their receptors.
      Therefore, advances in understanding of natriuretic peptide family genes and
      their regulatory mechanisms will lead to greater insight into the pathogenesis of
      cardiovascular diseases and blaze a new trail in clinical treatment.

PMID- 22382055
TI  - [Advances on molecular mechanisms of plant-pathogen interactions].
AB  - Plants have established a complicated immune defense system during co-evolution
      with pathogens. The innate immune system of plants can be generally divided into
      two levels. One, named PAMP-triggered immunity (PTI), is based on the recognition
      of pathogen-associated molecular patterns by pattern-recognition receptors, which
      confers resistance to most pathogenic microbes. The other begins in cytoplasm and
      mainly relies on recognition of microbial effectors by plant resistance proteins
      in direct or indirect ways, which then initiates potent defense responses. This
      process, termed effector-triggered immunity (ETI), is necessary for defense
      against pathogens that can secret effectors to suppress the first level of
      immunity. Activation of these two layers of immunity in plant is based on
      distinguishing and recognition of "self" and "non-self" signals. Recognition of
      "non-self" signals can activate signal cascades, such as MAPK cascades, which
      will then induce defense gene expression and corresponding defense responses. In
      this review, we focused on underlying molecular mechanisms of plant-pathogen
      interactions and the latest advances of the PTI and ETI signaling network.

PMID- 22382056
TI  - [Progress on whole genome sequencing in woody plants].
AB  - In recent years, the number of sequencing data of plant whole genome have been
      increasing rapidly and the whole genome sequencing has been also performed widely
      in woody plants. However, there are a set of obstacles in investigating the whole
      genome sequencing in woody plants, which include larger genome, complex genome
      structure, limitations of assembly, annotation, functional analysis, and
      restriction of the funds for scientific research. Therefore, to promote the
      efficiency of the whole genome sequencing in woody plants, the development and
      defect of this field should be analyzed. The three-generation sequencing
      technologies (i.e., Sanger sequencing, synthesis sequencing, and single molecule
      sequencing) were compared in our studies. The progress mainly focused on the
      whole genome sequencing in four woody plants (Populus, Grapevine, Papaya, and
      Apple), and the application of sequencing results also was analyzed. The future
      of whole genome sequencing research in woody plants, consisting of material
      selection, establishment of genetic map and physical map, selection of sequencing
      technology, bioinformatic analysis, and application of sequencing results, was
      discussed.

PMID- 22382057
TI  - [Population genetics of plant pathogens].
AB  - Comparing to natural ecosystems, the evolution of plant pathogens in agricultural
      ecosystems is generally faster due to high-density monocultures, large-scale
      application of agrochemicals, and international trade in agricultural products.
      Knowledge of the population genetics and evolutionary biology of plant pathogens
      is necessary to understand disease epidemiology, effectively breed and use
      resistant cultivars, and control plant diseases. In this article, we outlined the
      aims of population genetic studies in plant pathogens, discuss contributions of
      five evolutionary forces (i.e., mutation, gene flow, recombination, random
      genetic drift, and natural selection) to origin, maintenance, and distribution of
      genetic variation in time and space, and gave an overview of current research
      status in this field.

PMID- 22382058
TI  - [Organization, function and genetic controlling of synaptonemal complex].
AB  - The synaptonemal complex (SC) is a super protein lattice that connects paired
      homologous chromosomes in most meiotic systems. This special organization is
      related to the meiosis processes such as homologous chromosomes pairing,
      synapsis, recombination, segregation, etc. Flaws of it would lead the meiocytes
      to apoptosis, which contributes to sterility. In recent years, the study of this
      complex has been a hotspot in meiosis research, but little was known about its
      exact mechanism. This review summarized the organization, function, and genetics
      of this complex with recent advances. Prospects of its further study were also
      briefly discussed..

PMID- 22382059
TI  - [Progress in Cre/lox site-specific recombination system in higher eukaryotes].
AB  - Cre/lox system derived from P1 bacteriaphage can quickly and effectively achieve
      gene insertion, deletion, replacement, and inversion by means of site-specific
      recombination. As one of the most important tools for gene targeting at present,
      Cre/lox system has been widely used in Arabidopsis thaliana, Oryza sativa L., Mus
      musculus, Drosophila melanogaster, Danio rerio, and other higher eukaryotic
      organisms. This review roundly described the basic profile of Cre/lox system, and
      its application in higher eukaryotes. In addition, we also discussed the main
      problems and developmental trend of the Cre/lox system in this review, which can
      be a good reference for using Cre/lox system to realize the gene manipulations of
      the different high eukaryotic organisms.

PMID- 22382060
TI  - [Screening and identification of anoikis-resistant gene UBCH7 in esophageal
      cancer cells].
AB  - Anoikis is a kind of programmed cell death induced by loss of extracellular
      matrix (ECM) adhesion, which is one of key factors for homestasis. Resistance to
      anoikis is required for tumor cell metastasis. We have previously shown several
      anoikis-resistance genes in esophageal squamous cell carcinoma (ESCC). In order
      to find novel anoikis-resistant genes in ESCC, we constructed retroviral cDNA
      library using total RNA from ESCC cell lines. NIH 3T3 cells, which are sensitive
      to anoikis, were infected with the library constructed. The cells were cultured
      in soft agar, and the clones which can survive in detached states were selected.
      The cDNAs inserted into the anoikis-resistant NIH3T3 clones were amplified using
      retroviral specific primers. Sequencing analysis showed that a cDNA fragment
      inserted into the anoikis-resistant clone contains full coding sequence (ORF) of
      human UBCH7/UBE2L3 gene. By infection with retrovirus encoding UBCH7 ORF (pMSCV
      UBCH7), forced expression of UBCH7 increased the anoikis-resistance of NIH3T3
      cells. More importantly, knockdown of UBCH7 expression by siRNA transfection
      reduced the anoikis-resistant ability of esophageal cancer MLuC1 cells. The data
      suggest that UBCH7/UBE2L3 gene would be involved in anoikis-resistance in ESCC.

PMID- 22382061
TI  - [Analysis of gene expression profile of peripheral ganglia in early stage type II
      diabetic rats].
AB  - Diabetic neuropathy (DN) is defined as the presence of symptoms and/or signs of
      peripheral nerve dysfunction in people with diabetes. The aim of this study is to
      screen differentially expressed genes in peripheral ganglia in early stage type
      II experimental diabetic rats. We compared gene expression profiles of peripheral
      ganglia in type II diabetic and nondiabetic rats based on Illumina(r) Sentrix(r)
      BeadChip arrays. The results showed that 158 out of a total of 12 604 known genes
      were significantly differentially expressed, including 87 up-regulated and 71
      down-regulated genes, in diabetic rats compared with those in the nondiabetic
      rats. It is noted that some up-regulated genes are involved in the biological
      processes of neuronal cytoskeleton and motor proteins. In contrast, the down
      regulated genes are associated with the response to virus?biotic stimulus? other
      organism in diabetic rats. Kyoto Encyclopedia of Genes and Genomes (KEGG)
      analysis revealed that the most significant pathway enriched in the changed gene
      set is metabolism (P < 0.001). These results indicated that metabolic changes in
      peripheral ganglia of diabetic rats could be induced by hyperglycemia.
      Hyperglycemia could change the expression of genes involved in neuronal
      cytoskeleton and motor proteins through immune inflammatory response, and then
      impair the structure and function of the peripheral ganglia.

PMID- 22382062
TI  - [Molecular characteristics and specific PCR detection of transgenic rice
      containing Cry1Ab].
AB  - Bt01 is a new type of rice that has been genetically modified to express
      Cry1Abprotein. This study confirmed that Cry1Abwas inserted into Bt01 as a single
      copy using Southern blotting analysis. TAIL-PCR method was further used to obtain
      its insertion site information. Specific PCR primers and TaqMan probes were
      designed based on the 5'-integration junction sequence of transgenic rice Bt01.
      The results showed that the limit of detection (LOD) was ten copies in
      qualitative PCR. The quantitative PCR assay showed that the LOD was five copies,
      and the limit of quantification (LOQ) was ten cop-ies. In addition, the accuracy
      of the established quantitative PCR was verified by detecting two samples
      containing 3% and 0.5%Bt01, respectively. The quantitative PCR analysis showed
      the results were 2.7% and 0.47%, respectively.The above results indicated that
      the event-specific PCR methods developed have high specificity and good
      sensitivity, which could be effective methods for identifying and testing the
      genetically modified Bt01 rice.

PMID- 22382063
TI  - [Discovery of QTLs increasing yield related traits in common wild rice].
AB  - Common wild rice (Oryza rufipogon) is an important genetic resource. Discovery of
      desirable alleles in wild rice will make important contributions to rice genetic
      improvement. In this study, Zhenshan 97 as the recurrent parent and wild rice as
      the donor parent were used to develop a BC2F1 population. One plant BC2F1-15 in
      the population showed distinct phenotype from Zhenshan 97 was selected to produce
      a population of BC2F5 by continuous self-crossing. The genotype assay of the
      plant BC2F1-15 with 126 polymorphic SSR markers evenly distributed on 12
      chromosomes showed that it was heterozygous at 30% of the control marker loci.
      Four, 3, 4, 2, and 1 QTLs were detected for heading date, plant height, spikelets
      per panicle, grain weight, and single plant yield in the BC2F5 population,
      respectively. One QTL region flanked by the marker interval of RM481-RM2 on
      chromosome 7 had pleiotropic effects on heading date, spikelets per panicle, and
      grain yield per plant, and the alleles of wild rice increased phenotypic values.
      At the other 3 QTLs for spikelets per panicle, common wild rice had positive
      effects. These results clearly showed that common wild rice carried desirable
      alleles for yield related traits. The favorable alleles from common wild rice are
      new valuable genes for rice breeding.

PMID- 22382064
TI  - [Characteristics and molecular mapping of a novel chlorophyll-deficient yellow
      leaf mutant in rice].
AB  - A yellow-leaf mutant (yl11) with chlorophyll-deficient in rice (Oryza sativa L.)
      was selected from the progeny of a japonica rice variety "Jiahua 1" treated with
      60Co gamma-radiation. In comparison with the wild-type parent, "Jiahua 1", the
      mutant had yellow-leaves at whole growth stages and displayed significantly
      decreased in chlorophyll content and net photosynthetic rate. Underdeveloped
      chloroplast and alterations of the major agronomic traits, such as plant-heights,
      were also observed in the mutant. Genetic analysis confirmed that the yellow-leaf
      mutant trait was controlled by a single recessive nuclear gene (yl11). Using SSR
      and In/Del molecular markers and 920 F2 and F3 plants from the cross of yl11 with
      the indica variety Peiai 64S, the yl11 was mapped between the molecular markers
      MM2199 and InDel21039 with a physical distance of 110 kb on the long arm of
      chromosome 11, in which no known functional genes for chlorophyll synthesis or
      chloroplast development in rice has been found. These findings will provide a
      foundation for the cloning and functional analysis of this gene in the future.

PMID- 22382065
TI  - [Isolation and functional analysis of GsTIFY11b relevant to salt and alkaline
      stress from Glycine soja].
AB  - Using homologous cloning and RT-PCR technology, we isolated a novel TIFY family
      gene, GsTIFY11b, from Glycine soja L. G07256, a species that is tolerant to
      saline and alkaline environments. Phylogenetic analysis indicated that GsTIFY11b
      was closely related to AtTIFY11a with 56% similarity in amino acid identity.
      Protein sequence analysis showed that GsTIFY11b protein also had conserved TIFY
      domain, N-terminal domain, and a C-terminal Jas motif. Quantitative realtime PCR
      analysis indicated that the expression of GsTIFY11b was induced by both saline
      and alkaline stresses. Two homozygous GsTIFY11b over-expressing transgenic
      Arabidopsis lines were obtained. Phenotypic analysis of the transgenic and wild
      type Arabidopsis indicated that over-expressing GsTIFY11b in Arabidopsis did not
      enhance plant tolerance to saline and alkaline stresses, whereas it showed an
      increased sensitivity to saline stress during seed germination and seedling
      development. Expression analysis of saline stress response marker genes in
      transgenic and wild-type plants under stress condition indicated that GsTIFY11b
      regulated the expression of RD29B, KIN1, and DREB. The transient expression of a
      GsTIFY11b-GFP fusion protein in onion epidermal cells showed that GsTIFY11b was
      localized to the nucleus, suggesting a role as a transcriptional regulator in the
      saline stress response pathway.

PMID- 22382066
TI  - [Cloning and functional analysis of chitinase gene GbCHI from sea-island cotton
      (Gossypium barbadense)].
AB  - Chitinase is one of the important pathogenesis-related (PR) proteins in plants.
      By comparative proteomics study, a novel pathogen-responsive chitinase (known as
      GbCHI) has been identified from sea-island cotton (Gossypium barbadense). The
      GbCHI cDNA was cloned from wilt-resistant sea-island cotton and the anti-fungal
      activity of the gene product was investigated. qRT-PCR analysis indicated that
      GbCHI was expressed constitutively in root, stem, leaf, flower, and ovule of
      cotton plant, and the expression could be induced by Verticillium dahliae and
      plant hormone SA, ACC, and JA. Subcellular localization analysis using GFP-tagged
      proteins showed that GbCHI-GFP fusion proteins were targeted mainly to the plasma
      membrane. Anti-fungal assay demonstrated that GbCHI could inhibit spore
      germination and hyphae growth of V. dahliae significantly. These results provide
      important information for understanding the cellular function of GbCHI and for
      exploring the application potential of this gene in molecular breeding of wilt
      tolerant cotton plants.

PMID- 22382067
TI  - [From gene cloning to expressional analysis--practice and experience from
      educational reform of experimental gene engineering].
AB  - Experimental gene engineering is a laboratory course focusing on the molecular
      structure, expression pattern and biological function of genes. Providing our
      students with a solid knowledge base and correct ways to conduct research is very
      important for high-quality education of genetic engineering. Inspired by recent
      progresses in this field, we improved the experimental gene engineering course by
      adding more updated knowledge and technologies and emphasizing on the combination
      of teaching and research, with the aim of offering our students a good start in
      their scientific careers.

PMID- 22382068
TI  - Inhibition of farnesyltransferase reduces angiogenesis by interrupting
      endothelial cell migration.
AB  - Inhibitors of farnesyltransferase (FTI) have been developed for cancer treatment
      for more than a decade. Aside from being a therapeutic target in tumor cells,
      little is known about the role of farnesyltransferase (FTase) in other
      physiological processes. In this study, we revealed the involvement of FTase in
      angiogenesis and showed that FTI inhibited angiogenesis by directly acting on
      endothelial cells. Inhibition of FTase interrupted cell migration in vitro and in
      vivo. In addition, we found that FTase was important for cell polarization, cell
      spreading and pseudopodia formation. We also found that FTase interacted with
      microtubule end binding protein 1 (EB1) and that this interaction was critical
      for the localization of EB1 to microtubule tips. Our findings thus offer novel
      insight into the functions of FTase in endothelial cells and provide valuable
      information for the use of FTI in cancer therapy.

PMID- 22382069
TI  - Finding the right kind of support: a study of carers of those with a primary
      malignant brain tumour.
AB  - PURPOSE: Caring for someone with a primary malignant brain tumour is very
      demanding due to the dynamic situation involving changes to personality, short
      term memory loss and changes in family relationships. The purpose of this
      qualitative study is to examine the support needs of carers of those with a
      primary malignant brain tumour. METHODS & SAMPLE: 22 Carers who were currently
      caring for someone with a primary malignant brain tumour were recruited from one
      specialist cancer centre in the south east of England. The study took a grounded
      theory approach and data were analysed using the constant comparative method
      generating categories and themes that are grounded in the data. KEY RESULTS: A
      key concept that emerged from the data was: 'Connecting on the caring journey'.
      The themes that emerged from the key concept were: building helpful
      relationships; safe places and comfort zones; and threats to connecting.
      CONCLUSIONS: Many carers do find a great deal of support within the family and
      from their relationships with friends as well as from cancer and carer support
      groups. However this is by no means universal and many carers experience a lack
      of timely access to good quality supportive care services. For some carers
      supportive care services do not meet their expectations so they spend valuable
      time searching for the connections they need to continue to care combined with
      feeling frustrated and under pressure.

PMID- 22382070
TI  - Nitrogen fertilizer improves boron phytoextraction by Brassica juncea grown in
      contaminated sediments and alleviates plant stress.
AB  - In this study we evaluated the effect of different fertilizer treatments on
      Brassica plants grown on boron-contaminated sediments. Experiments were conducted
      in the laboratory and on the lysimeter scale. At laboratory scale (microcosm),
      five different fertilizers were tested for a 35-d period. On the lysimeter scale,
      nitrogen fertilization was tested at three different doses and plants were
      allowed to grow until the end of the vegetative phase (70 d). Results showed that
      nitrogen application had effectively increased plant biomass production, while B
      uptake was not affected. Total B phytoextracted increased three-fold when the
      highest nitrogen dose was applied. Phytotoxicity on Brassica was evaluated by
      biochemical parameters. In plants grown in unfertilized B-contaminated sediments,
      the activity of antioxidant enzymes superoxide dismutase (SOD), ascorbate
      peroxidase (APX) and pyrogallol peroxidase (PPX) increased, whereas catalase
      (CAT) decreased with respect to control plants. Addition of N progressively
      mitigated the alteration of enzymatic activity, thus suggesting that N can aid in
      alleviating B-induced oxidative stress. SOD activity was restored to control
      levels just at the lowest N treatment, whereas the CAT inhibition was partially
      restored only at the highest one. N application also lowered the B-induced
      increase in APX and PPX activities. Increased glutathione reductase activity
      indicated the need to restore the oxidative balance of glutathione. Data also
      suggest a role of glutathione and phytochelatins in B defense mechanisms. Results
      suggest that the nitrogen fertilizer was effective in improving B phytoextraction
      by increasing Brassica biomass and by alleviating B-induced oxidative stress.

PMID- 22382071
TI  - FDA proposes to ban cephalosporins from livestock feed.

PMID- 22382072
TI  - Layer-dependent fluorination and doping of graphene via plasma treatment.
AB  - In this work, the fluorination of n-layer graphene is systematically investigated
      using CHF3 and CF4 plasma treatments. The G and 2D Raman peaks of graphene show
      upshifts after each of the two kinds of plasma treatment, indicating p-doping to
      the graphene. Meanwhile, D, D' and D + G peaks can be clearly observed for
      monolayer graphene, whereas these peaks are weaker for thicker n-layer graphene
      (n >= 2) at the same experimental conditions. The upshifts of the G and 2D peaks
      and the ratio of I(2D)/I(G) for CF4 plasma treated graphene are larger than those
      of CHF3 plasma treated graphene. The ratio of I(D)/I(G) of the Raman spectra is
      notably small in CF4 plasma treated graphene. These facts indicate that CF4
      plasma treatment introduces more p-doping and fewer defects for graphene.
      Moreover, the fluorination of monolayer graphene by CF4 plasma treatment is
      reversible through thermal annealing while that by CHF3 plasma treatment is
      irreversible. These studies explore the information on the surface properties of
      graphene and provide an optimal method of fluorinating graphene through plasma
      techniques.

PMID- 22382073
TI  - Sensitive detection of endonuclease activity and inhibition using gold nanorods.
AB  - It is important to develop reliable and sensitive methods for assay of nuclease
      activity. With this goal in mind, we report a new strategy for nuclease assay by
      taking advantage of efficient fluorescence resonance energy transfer (FRET)
      between gold nanorods (GNRs) and fluorescein-tagged single-stranded DNA (FDNA).
      Upon mixing with GNRs, the FRET between positively charged GNRs and negatively
      charged FDNA caused a decrease in fluorescence of FDNA. The formation of
      FDNA/cDNA duplex further improved the FRET efficiency, leading to a significant
      decrease in fluorescence intensity. However, fluorescence is restored when
      FDNA1/cDNA1 hybrid was cleaved into small fragments by EcoRI endonucleases,
      resulting in a decrease in FRET efficiency because of weakened electrostatic
      interaction between GNRs and the shortened DNA fragments. Activity of EcoRI
      endonuclease has been real-time studied by monitoring fluorescence change with
      the prolonging of interaction time. Under optimized conditions, the cleaved
      fraction is linear with EcoRI concentration over the range of 1.0*10(-3) to
      1.0*10(-1) U MUL(-1), with a limit of detection of 6.5*10(-4) U MUL(-1) which is
      much better or at least comparable to previous reports. Site-specific DNA
      cleavage by EcoRI endonuclease has also been verified by gel electrophoresis,
      fluorescence anisotropy and TEM analysis, which indicated that this method is a
      feasible and reasonable approach to study sequence-specific protein-DNA
      interactions. Assay of BamHI activity demonstrated that it is a more universally
      applied method for studying the activity of endonuclease. Furthermore, this
      fluorescence assay has been also used for studying the inhibition of EcoRI
      endonuclease activity. Importantly, experimental results suggested that
      endonuclease inhibitors can be screened by monitoring the change of fluorescence
      change. Therefore, this FRET assay is a simple, sensitive and effective approach
      to study endonuclease activity and inhibition, and as such, it promises to
      provide a feasible method to screen nuclease inhibitors.

PMID- 22382074
TI  - An ultrasensitive fluorescent aptasensor for adenosine detection based on
      exonuclease III assisted signal amplification.
AB  - We report here a graphene oxide (GO)-based fluorescent aptasensor for adenosine
      detection by employing exonuclease III (Exo III) as a signal amplifying element.
      In the absence of adenosine, the adenosine aptamers hybridized with the
      complementary DNA (cDNA), and the Exo III could not cleave the single-strand
      signal probes labeled with carboxylfluorescein (FAM) at its 5' ends. When the
      graphene oxide was finally added, it could strongly adsorb the single-strand
      signal probes and quenched the fluorophore effectively. In the presence of
      adenosine, the aptamers associated with the targets, which led to the formation
      of duplex DNAs between the cDNAs and the signal probes. The Exo III thereafter
      could digest the duplex DNAs from 3' blunt terminus of signal probes, liberating
      the fluorophore. Upon adding the GO, the fluorophore could not be adsorbed and
      quenched. By coupling cyclic enzymatic cleavage, a remarkable fluorescent
      increase was obtained. Due to the specific recognition ability of the aptamer for
      the target and the powerful quenching property of GO for signal probe, this
      proposed approach has a good selectivity and high sensitivity for adenosine. In
      the optimum conditions described, >100% signal enhancement was achieved and a
      limit of detection as low as 1 nM was obtained, which is lower than those of
      commonly used fluorescent aptamer sensors. Moreover, the biosensor exhibited an
      ultrahigh sensitivity and held a versatile platform for clinical diagnostics,
      molecular biology and drug developments.

PMID- 22382075
TI  - Low-level environmental cadmium exposure is associated with DNA hypomethylation
      in Argentinean women.
AB  - BACKGROUND: Cadmium, a common food pollutant, alters DNA methylation in vitro.
      Epigenetic effects might therefore partly explain cadmium's toxicity, including
      its carcinogenicity; however, human data on epigenetic effects are lacking.
      OBJECTIVE: We evaluated the effects of dietary cadmium exposure on DNA
      methylation, considering other environmental exposures, genetic predisposition,
      and gene expression. METHODS: Concentrations of cadmium, arsenic, selenium, and
      zinc in blood and urine of nonsmoking women (n = 202) from the northern
      Argentinean Andes were measured by inductively coupled mass spectrometry.
      Methylation in CpG islands of LINE-1 (long interspersed nuclear element-1; a
      proxy for global DNA methylation) and promoter regions of p16 [cyclin-dependent
      kinase inhibitor 2A (CDKN2A)] and MLH1 (mutL homolog 1) in peripheral blood were
      measured by bisulfite polymerase chain reaction pyrosequencing. Genotyping (n =
      172) for the DNA (cytosine-5-)-methyltransferase 1 gene (DNMT1 rs10854076 and
      rs2228611) and DNA (cytosine-5-)-methyltransferase 3 beta gene (DNMT3B rs2424913
      and rs2424932) was performed with Sequenom iPLEX GOLD SNP genotyping; and gene
      expression (n = 90), with DirectHyb HumanHT-12 (version 3.0). RESULTS: Cadmium
      exposure was low: median concentrations in blood and urine were 0.36 and 0.23
      ug/L, respectively. Urinary cadmium (natural log transformed) was inversely
      associated with LINE-1 methylation (beta = -0.50, p = 0.0070; beta = -0.44, p =
      0.026, adjusted for age and coca chewing) but not with p16 or MLH1 methylation.
      Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations
      between urinary cadmium and LINE-1 (p-values for interaction in adjusted models
      were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger
      hypomethylation with increasing urinary cadmium concentrations. Cadmium was
      inversely associated with DNMT3B (r(S) = -0.28, p = 0.0086) but not with DNMT1
      expression (r(S) = -0.075, p = 0.48). CONCLUSION: Environmental cadmium exposure
      was associated with DNA hypomethylation in peripheral blood, and DNMT1 genotypes
      modified this association. The role of epigenetic modifications in cadmium
      associated diseases needs clarification.

PMID- 22382076
TI  - Kainic acid-induced changes in the opioid/nociceptin system and the
      stress/toxicity pathways in the rat hippocampus.
AB  - Excitotoxicity is a contributing factor to the pathogenesis of acute or chronic
      neurodegenerative disease states. Kainic acid (KA) is an excitotoxic substance
      and the administration of it to rodents induces seizure activity (status
      epilepticus, SE) and leads to neurodegeneration. In this study the effect of KA
      induced excitotoxicity on the G-protein activations and the gene expression
      levels of the opioid/nociceptin system receptors as MOPr, KOPr, DOPr, ORL-1, and
      PNOC (N/OFQ) were investigated, and the regulator effect of naloxone (Nal) on the
      gene expressions of the opioid system receptors against KA-induced seizures in
      the rat hippocampus was tested. In addition, the expression levels of stress
      toxicity genes were assessed in the hippocampus following KA-induced
      excitotoxicity in order to determine the potential genetic targets which can be
      helpful for neuroprotective interventions. Our results indicate that the KA
      induced excitotoxicity increased the mRNA levels of MOPr, DOPr, KOPr, PNOC, and
      ORL-1. However, G-protein activations of MOPr, DOPr, and KOPr remained relatively
      unchanged while both the potency and efficacy of N/OFQ were significantly
      increased. The PCR array data showed that KA-induced excitotoxicity altered the
      expression levels of genes in the cellular stress or toxicity pathways. Our data
      suggests that the induction of the opioid/nociceptin system may be involved in
      the cellular stress response following a neurodegenerative insult and that the
      genes modulated by the KA-treatment in the stress-toxicity pathways may be
      evaluated as targets of potential neuroprotective interventions.

PMID- 22382077
TI  - Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure:
      role of glutamine redefined.
AB  - Acute liver failure (ALF) is characterized neuropathologically by cytotoxic brain
      edema and biochemically by increased brain ammonia and its detoxification
      product, glutamine. The osmotic actions of increased glutamine synthesis in
      astrocytes are considered to be causally related to brain edema and its
      complications (intracranial hypertension, brain herniation) in ALF. However
      studies using multinuclear (1)H- and (13)C-NMR spectroscopy demonstrate that
      neither brain glutamine concentrations per se nor brain glutamine synthesis rates
      correlate with encephalopathy grade or the presence of brain edema in ALF. An
      alternative mechanism is now proposed whereby the newly synthesized glutamine is
      trapped within the astrocyte as a consequence of down-regulation of its high
      affinity glutamine transporter SNAT5 in ALF. Restricted transfer out of the cell
      rather than increased synthesis within the cell could potentially explain the
      cell swelling/brain edema in ALF. Moreover, the restricted transfer of glutamine
      from the astrocyte to the adjacent glutamatergic nerve terminal (where glutamine
      serves as immediate precursor for the releasable/transmitter pool of glutamate)
      could result in decreased excitatory transmission and excessive neuroinhibition
      that is characteristic of encephalopathy in ALF. Paradoxically, in spite of
      renewed interest in arterial ammonia as a predictor of raised intracranial
      pressure and brain herniation in ALF, ammonia-lowering agents aimed at reduction
      of ammonia production in the gut have so far been shown to be of limited value in
      the prevention of these cerebral consequences. Mild hypothermia, shown to prevent
      brain edema and intracranial hypertension in both experimental and human ALF,
      does so independent of effects on brain glutamine synthesis; whether or not
      hypothermia restores expression levels of SNAT5 in ALF awaits further studies.
      While inhibitors of brain glutamine synthesis such as methionine sulfoximine,
      have been proposed for the prevention of brain edema in ALF, potential adverse
      effects have so far limited their applicability.

PMID- 22382079
TI  - Risk of gambling onset in youth who are younger than same-grade peers.
AB  - PURPOSE: To assess whether a child's age relative to the median age of classmates
      in the same grade is associated with the onset of gambling. METHODS: Grade 7
      students (n = 647) from 10 Montreal secondary schools were followed for 8 years.
      Relative age was expressed as years above or below the school-specific grade 7
      median age. Hazard ratios and 95% confidence intervals (CI) were estimated for
      the association between relative age and age of gambling onset, with adjustment
      for sex, ethnicity, parent education, and impulsivity. RESULTS: A greater
      proportion of students in the youngest quartile gambled compared with the oldest
      (85.8% vs 74.7%). Hazards of gambling onset for students younger than the median
      age were elevated after age 10.5 years, but hazards were protective beforehand.
      At age 17 years, for example, the hazard for gambling onset was 61% greater (95%
      CI 1.4-1.9) for youth who were 1 year younger, but at age 8 years the hazard was
      23% lower (95% CI 0.7-0.9). CONCLUSIONS: Younger relative age may be a risk
      factor for gambling onset in older youth.

PMID- 22382080
TI  - Gestational age at birth and risk of gastric acid-related disorders in young
      adulthood.
AB  - PURPOSE: Preterm birth is associated with gastric acid-related disorders in
      infancy, but no investigators have examined this association beyond early
      childhood. We used antisecretory medication data to explore whether preterm birth
      is associated with gastric acid-related disorders in young adulthood. METHODS: We
      conducted a national cohort study of 626,811 individuals born in Sweden in 1973
      to 1979, followed up for antisecretory (proton pump inhibitor and H2-receptor
      antagonist) medication prescriptions from all outpatient and inpatient pharmacies
      nationwide from 2005 to 2009 (ages 25.5-37.0 years). We excluded individuals with
      congenital anomalies, and examined potential confounding by other comorbidities
      identified on the basis of oral anti-inflammatory or corticosteroid medication
      prescription. RESULTS: Gestational age at birth was inversely associated with
      antisecretory medication prescription in young adulthood. Adjusted odds ratios
      for >=1 antisecretory medication prescription/year were 3.38 (95% confidence
      interval [95% CI], 1.73-6.62) for individuals born at 22-27 weeks, 1.38 (95% CI,
      1.19-1.60) for those born at 28-34 weeks, and 1.19 (95% CI, 1.06-1.32) for those
      born at 35-36 weeks, relative to those born full-term (37-42 weeks). Exclusion of
      individuals who were prescribed oral anti-inflammatory or corticosteroid
      medications (>=1/year) had little effect on these results. CONCLUSIONS: These
      findings suggest that low gestational age at birth may be independently
      associated with an increased risk of gastric acid-related disorders in young
      adulthood.

PMID- 22382081
TI  - Gene-environment interaction between interleukin-4 promoter and molds in
      childhood asthma.
AB  - PURPOSE: To assess the role of gene-environment interaction between interleukin
      (IL)-4 promoter and mold exposure on the development of asthma. METHODS: We
      conducted a cohort-based, incident, case-control study. The case group consisted
      of 188 children with new asthma and the control group (n = 376) was matched for
      age and gender. The outcome of interest was the development of asthma over the 6
      year study period. The studied determinants were three polymorphisms of IL-4
      promoter (TT, CT, and CC) and three indicators of exposure including histories of
      water damage, presence of visible molds, and perceived mold odor in the home.
      RESULTS: Apparent joint effects between IL-4 promoter and mold exposure were
      observed on both additive and multiplicative scales. Specially, the risk of
      asthma was significantly associated with children carrying the CT genotype and
      visible mold exposure comparing with those carrying the TT genotype without any
      exposure indicator (adjusted odds ratio [OR], 2.14; 95% confidence interval [CI],
      1.05-4.34; modified Rothman synergy index for directly use of odds and OR [s] =
      1.41; P for interaction = .03). A similar tendency was found (s = 1.30; P for
      interaction = .04) for children who were exposed to mold odor and carried CT
      genotype (adjusted OR, 1.99; 95% CI, 1.03-4.41). CONCLUSIONS: The results of this
      study suggest that gene-environment interactions between the IL-4 promoter and an
      indoor mold problem may play an important role in childhood asthma.

PMID- 22382082
TI  - Prevalence and 5-year incidence of dual sensory impairment in an older Australian
      population.
AB  - PURPOSE: To report prevalence and 5-year incidence of dual sensory impairment
      (DSI), and associated risk factors, in an older population. METHODS: We included
      2015 Blue Mountains Hearing Study participants aged >=55 years, examined between
      1997 and 1999 (baseline) and 2002 and 2004. Hearing thresholds were measured with
      the use of pure-tone audiometry. Visual acuity was measured with a LogMar chart
      while the subject wore distance glasses, if they owned a pair. DSI was defined as
      combined presenting visual acuity (better eye) <20/40, and PTA(0.5-4 kHz) (better
      ear) >25 dB HL. The incidence of DSI was considered by the use of two at-risk
      subpopulations: (i) participants with no sensory impairment and; (ii) with one
      type of sensory impairment at baseline. RESULTS: The prevalence of DSI was 6% at
      baseline, increasing from 0% for ages <60 years to 26.8% for ages 80+ years (p
      for trend <.0001). Five-year DSI incidence was 1.6% in persons with no sensory
      impairment and 11.3% in those with a single sensory impairment, a 7-fold
      difference. Among participants with either no sensory impairment or a single
      sensory impairment at baseline, a significant age-related increase in incident
      DSI was found (p for trend <.0001 and .0004, respectively). Low education was a
      significant risk factor for DSI among those with no sensory impairment and those
      with single sensory impairment, multivariable-adjusted odds ratio (OR, 6.62; 95%
      confidence interval [95% CI], 1.79-24.4) and OR, 2.55 (95% CI, 1.36-4.79),
      respectively. CONCLUSIONS: Aging population trends and the age-related prevalence
      and incidence of DSI support the implementation of collaborative efforts in
      service provision between hearing and vision professionals. Active case-finding
      among older persons with single-sensory impairments may help identify those with
      DSI and provide timely and appropriate services.

PMID- 22382083
TI  - Management-changing errors in the recall of radiologic results - a pilot study.
AB  - AIM: To evaluate the occurrence of alterations to diagnostic information from
      radiological studies, which are altered by person-to-person communication and/or
      faulty recall, and whether they affect patient management MATERIALS AND METHODS:
      A structured telephone survey was conducted at a large tertiary care medical
      centre of house staff managing inpatients who had undergone chest, abdominal, or
      pelvic computed tomography (CT) or magnetic resonance imaging (MRI) and remained
      in the hospital at least 2 days later. Fifty-six physicians were surveyed
      regarding 98 patient cases. Each physician was asked how he or she first became
      aware of the results of the study. Each was then asked to recall the substance of
      radiological interpretation and to compare it with the radiology report. Each was
      then asked to assess the level of difference between the interpretations and
      whether management was affected. Results were correlated with the route by which
      interviewees became aware of the report, the report length, and whether the
      managing service was medical or surgical. RESULTS: In nearly 15% (14/98) of
      cases, differences between the recalled and official results were such that
      patient management could have been (11.2%) or had already been affected (3.1%).
      There was no significant correlation between errors and either the route of
      report communication or the report length. CONCLUSION: There was a substantial
      rate of error in the recall and/or transmission of diagnostic radiological
      information, which was sufficiently severe to affect patient management.

PMID- 22382084
TI  - The mesosternum of the Regourdou 1 Neandertal revisited.
AB  - Fossil hominin mesosterna, while scarce, can provide useful morphological data in
      addition to rib remains regarding aspects of thoracic size and shape. These data,
      in turn, can address hypotheses related to respiratory dynamics, climatic
      adaptation, and ecogeographical patterning. In this study, we re-evaluate the
      anatomical representation of the mesosternum of the Regourdou 1 Neandertal
      individual that alters key aspects of the original description of the fossil
      remains. We compare this specimen together with the mesosterna of the Kebara 2
      Neandertal male individual and the Tabun C1 Neandertal female individual to a
      large extant modern sample. Our study shows that the current evidence available
      for Neandertals indicates longer mesosterna, reflecting larger thorax sizes among
      Neandertals, in comparison with extant humans. Additionally, while this study
      weakens previous suggestions of ecogeographically mediated differences in the
      size and shape of upper thorax between Neandertals from the Mediterranean Levant
      and those deriving from Western Europe, we cannot unambiguously disprove the
      notion of such clinal differences.

PMID- 22382085
TI  - Insights into stem cell factor chemotactic guidance of neural crest cells
      revealed by a real-time directionality-based assay.
AB  - The extracellular environment through which neural crest cells (NCCs) translocate
      and differentiate plays a crucial role in the determination of cell migration and
      homing. In the trunk, NCC-derived melanocyte precursor cells (MPCs) take the
      dorsolateral pathway and colonize the skin, where they differentiate into pigment
      cells (PCs). Our hypothesis was that the skin, the MPCs' target tissue, may
      induce a directional response of NCCs toward diffusible factor(s). We show that
      the treatment of in vitro NCCs with skin extract (SE) or Stem Cell Factor (SCF)
      contributes to maintaining proliferative activity, accelerates melanocyte
      differentiation, and guides a subpopulation of NCCs by chemotaxis toward the
      gradient source of these factors, suggesting that they may represent the MPCs'
      subpopulation. Current data on stimulated directional persistence of NCCs
      supports the participation of diffusible molecules in the target colonization
      mechanism, guiding MPCs to migrate and invade the skin. Our results show similar
      effects of SE and SCF on NCC growth, proliferation and pigment cell
      differentiation. Also, the use of a proven real-time directionality-based
      objective assay shows the directional migration of NCCs toward SE and SCF,
      indicating that the epidermal SCF molecule may be involved in the chemotactic
      guidance mechanism of in vivo NCCs. Although SCF is the strongest candidate to
      account for these phenomena, the nature of other factor(s) affecting NCC-oriented
      migration remains to be investigated. This data amplifies the functional scope of
      trophic factors by involving them in new cell behaviors such as molecular
      guidance in the colonization mechanism of embryonic cells.

PMID- 22382086
TI  - [The trendelenburg position in the urgent treatment of the hypotensive patient:
      empiricism versus rationalism].

PMID- 22382087
TI  - Comparative dosimetric and radiobiological assessment among a nonstandard
      RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D
      brachytherapy for the treatment of the vaginal vault in patients affected by
      gynecologic cancer.
AB  - To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate
      brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with
      gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard
      (without vaginal applicator) RapidArc plans for 27 women with GC were developed
      to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were
      performed by means of dose-volume histogram and equivalent uniform dose (EUD) for
      planning target volume (PTV) and organs at risk (OARs). In addition, the integral
      dose and the overall treatment times were evaluated. RA, as well as IMRT, results
      in a high uniform dose on PTV compared with HDR-BRT. However, the average of EUD
      for HDR-BRT was significantly higher than those with RA and IMRT. With respect to
      the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT.
      Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and
      better than HDR-BRT for the rectum because of a significant reduction of d(2cc),
      d(1cc), and d(max) (p < 0.01). Integral doses were always higher than HDR-BRT,
      although the values were very low. Delivery times were about the same and more
      than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion,
      the boost of dose on vaginal vault in patients affected by GC delivered by a
      nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT
      because of a reduction of delivery time and rectal dose at substantial comparable
      doses for the bladder and sigmoid. However HDR-BRT provides better performance in
      terms of PTV coverage as evidenced by a greater EUD.

PMID- 22382088
TI  - MMP mediated type V collagen degradation (C5M) is elevated in ankylosing
      spondylitis.
AB  - OBJECTIVES: Type V collagen has been demonstrated to control fibril formation.
      The aim of this study was to develop an ELISA capable of detecting a fragment of
      type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for
      ankylosing spondylitis (AS). DESIGN AND METHODS: A fragment unique to type V
      collagen and generated by both MMP-2/9 cleaved at the amino acid position 1317
      (C5M) was selected for ELISA development. 40 AS patients and 40 age-matched
      controls were evaluated. RESULTS: An ELISA detecting C5M with inter- and intra
      assay variations of 9.1% and 4.4% was developed. C5M levels were significantly
      higher in AS patients compared to controls, 229% (p<0.0001). The diagnostic AUC
      was 83%. CONCLUSIONS: This ELISA is the first for detecting type V collagen
      degradation. AS patients had highly elevated levels of MMP mediated type V
      collagen degradation. The prognostic and diagnostic values need to be further
      investigated in additional clinical settings.

PMID- 22382089
TI  - On rat poison and human medicines: personalizing warfarin therapy.
AB  - Teaching old dogs new tricks is difficult, but lessons learned from such efforts
      can be invaluable. Warfarin is an old drug, difficult to administer and a leading
      cause of drug-related mortality and hospitalizations. New genetic tests for
      optimizing warfarin therapy have not been adopted. The debate over precise
      clinical utility and cost-effectiveness of these tests misses more important
      points of building a better, cheaper, and more efficient infrastructure to
      measure the true real-world impact of personalized medicine. However, this same
      debate about how, when, and where such testing is appropriate has been invaluable
      to the field of personalized medicine: progress beyond science, in policy,
      regulations, and logistics can be highlighted along the path to safer and more
      efficacious warfarin therapy.

PMID- 22382090
TI  - Clinical use of phosphorylated proteins in blood serum analysed by immobilised
      metal ion affinity chromatography and mass spectrometry.
AB  - The process of protein phosphorylation in cells is well studied in the context of
      a wide range of biologic functions such as signalling, cell cycle, cell growth
      and differentiation, and others. In contrast, little progress has been made in
      the investigation of protein phosphorylation specifically in blood. Here, we
      focussed on the phosphoproteome in human blood serum to study its extent and
      characteristics, and to explore the potential clinical utility. Immobilised metal
      ion affinity chromatography (IMAC) for the enrichment of intact phosphorylated
      proteins and label-free liquid chromatography-mass spectrometry (LC-MS(E)) were
      used for the molecular analysis of a large number of serum samples. To obtain
      high-confidence results, phosphorylated peptides had to be detected in at least 2
      out of 3 technical replicates per sample and in >70% of the serum samples drawn
      from 80 volunteers. Individual analysis of these 80 non-pooled samples resulted
      in the detection of 5825 unique phosphorylated peptides after filtering, which
      corresponded to 502 unique proteins. The results provided evidence that blood
      serum may be an untapped source of phosphoproteins suitable for potential use in
      understanding disease pathophysiology and for identification of disease and drug
      response biomarkers. This article is part of a Special Issue entitled: Integrated
      omics.

PMID- 22382091
TI  - Comparison of three different C18 HPLC columns with different particle sizes for
      the optimization of aflatoxins analysis.
AB  - In this work we compared the performance of chromatography columns with particles
      of 5 and 3 MUm with the new 2.7 MUm solid core particles for the analysis of
      aflatoxins B1, G1, B2, and G2 using trifluoroacetic acid pre-column
      derivatization. Three different columns have been used and chromatographic
      parameters as retention time, resolution, limit of detection (LOD), limit of
      quantification (LOQ) were obtained from all of them and compared. The results
      show that comparing with the traditional columns, shorter columns (100 mm * 4.6
      mm) with the new solid core particles are suitable for the analysis of these
      mycotoxins and allowed the reduction of the analysis time by 45.5% and 33.3% with
      respect to columns with particle size 5 MUm (150 mm * 4.6 mm) and 3 MUm (150 mm *
      4.6 mm) respectively, without any detrimental effect on performance. This leads
      to the reduction of the analysis costs by saving on organic solvents and
      increasing the total number of analyses per day. The capability of these columns
      for analyzing samples, in different culture media, was assessed by analyzing
      different samples from: yeasts extract sucrose medium, corn meal agar medium and
      fresh hazelnut media.

PMID- 22382092
TI  - Molecular imprinting based composite cryogel membranes for purification of anti
      hepatitis B surface antibody by fast protein liquid chromatography.
AB  - In the present study, we have focused our attention to prepare molecular
      imprinted composite cryogel membranes for purification of hepatitis B surface
      antibody (anti-HBs) by fast protein liquid chromatography. Before the preparation
      of the molecular imprinted composite cryogel membranes (MI-CMs) by free radical
      polymerization at sub-zero temperature, we have synthesized and characterized the
      anti-HBs imprinted particles. Then, the cryogel membranes (CMs) were
      characterized by swelling test, scanning electron microscopy and Fourier
      transform infrared spectroscopy. Prior to chromatographic purification studies,
      the effective parameters on the anti-HBs adsorption process were evaluated by
      investigating the dependency of the adsorption capacity on flow-rate, anti-HBs
      concentration, contact time and ionic strength. The maximum anti-HBs adsorption
      capacity was calculated as 701.4 mIU/g CM. The selectivity of the MI-CMs was
      shown by competitive adsorption of anti-HBs, total anti-hepatitis A antibody
      (anti-HAV) and total immunoglobulin E (IgE) adsorption studies. The MI-CMs have
      relative selectivity coefficients as 5.45 for anti-HBs/total anti-HAV and 9.05
      for anti-HBs/total IgE, respectively. The phosphate buffer solution (pH 7.4)
      containing 1.0M NaCl was used for elution, almost completely, of adsorbed anti
      HBs molecules. The MI-CMs could be used many times without any significant
      decrease in the adsorption capacity. The chromatographic purification
      performances of the MI-CMs were also investigated. The chromatographic parameters
      such as capacity and separation factors, the theoretical plate number and
      resolution of the MI-CMs were calculated as 5.48, 6.02, 1153.9, and 1.72 for anti
      HBs molecules, respectively. As a conclusion, we can say that the MI-CMs could be
      used for specific purification of anti-HBs from anti-HBs positive human plasma.

PMID- 22382094
TI  - Examining assumptions about female dominance in autoimmune disease.

PMID- 22382093
TI  - A sensitive HPLC-based method to quantify adenine nucleotides in primary
      astrocyte cell cultures.
AB  - In mono-layered primary cell cultures baseline AMP and ADP levels are found
      nominally in the mid to low picomolar range and are thus difficult to measure
      with conventional HPLC methods that often require the pooling of samples or
      require indirect detection methods using radiotracers or enzyme coupled assays.
      To address this issue, we developed a highly sensitive and selective ion-pairing
      HPLC method with fluorescence detection to quantify adenine nucleotides and the
      adenylate energy charge in primary astrocyte cell cultures. To accomplish this,
      we optimized the fluorescence derivatization conditions and the HPLC parameters
      to achieve baseline separation and quantification of all adenine nucleotides.
      Nucleotides were converted to their respective 1, N(6)-etheno derivatives by
      incubating with chloroacetaldehyde at pH 4.5 and 60 degrees C for 60 min. Under
      these conditions, the loss of the adenine nucleotides due to hydrolysis was
      minimized with a derivatization yield of 94.1% for 1, N(6)-ethenoadenosine. The
      optimal concentration of tetrabutylammonium phosphate, the ion-pairing reagent,
      required to achieve a reproducible separation of the adenine nucleotides was
      found to be 0.8mM. Calibration curves of nucleotide standards were linear within
      the range of 0.16-10.4 pmol for adenosine, 0.16-20.6 pmol for AMP, 0.15-19.2 pmol
      for ADP, and 0.15-19.5 pmol for ATP. The limits of detection and quantification
      for all adenine nucleotides were approximately 0.08 and 0.16 pmol, respectively.
      The intra- and inter-day variability for this method was less than 5.1 and 3.4%,
      respectively. This method was successfully used to measure all adenine
      nucleotides and an adenylate energy charge of 0.92+/-0.02 in primary astrocyte
      cell cultures.

PMID- 22382095
TI  - Septic arthritis of the hip joint in children is an emergency.

PMID- 22382096
TI  - Foreign body in the ear, nose and throat in children: A five year review in Niger
      delta.
AB  - BACKGROUND: Foreign body (FB) injury in children is becoming increasingly common
      in developing countries. Children tend to be curious and exploratory hence the
      easily accessible orifices tend to be at risk of this form of injury. This study
      is to determine the prevalence, treatment outcome and complication of foreign
      body injury to the ear, nose and throat in children. MATERIALS AND METHODS: A
      retrospective study of all pediatric patients with FB in the ear, nose and throat
      (ENT) seen at the ENT surgery department and children emergency ward of our
      institution from January 2004 to December 2008. Demographic and clinical data
      were obtained from records of the patients and analyzed. RESULTS: There were 202
      children with ENT injuries within the period under study, 181 (89.60%) had FB
      injuries. There were 94 males (51.93%), 87 females (48.07%) male:female ratio of
      1.1:1. Age ranged from 2 months -15 years with a mean of 3.71 +/- 2.59 years, a
      mode of 3 years. Most of the patients were below age seven years, highest in the
      range 0-3 years (61.8%). The nose recorded the highest injury 88 (48.62%).
      Commonest FB was ornamental bead 51 (28.17%) found both in the ear and the nose.
      Fish bone constituted the highest FB in the laryngotracheobronchial (LTB) tree
      and the oesophagus. Twenty-three cases (12.7%) had emergency tracheostomy done.
      CONCLUSION: Foreign body injuries constitute a significant portion of pediatric
      ENT trauma in clinical practice. The under 3 years are most affected. There is
      need for more public education of parents and care givers so as to prevent this
      avoidable injury.

PMID- 22382097
TI  - Feasibility of a tubularised incised-plate urethroplasty with double de
      epithelised dartos flaps in a failed hypospadias repair: a preliminary report.
AB  - BACKGROUND: Reoperation for failed hypospadias has been considered to be
      seriously problematic. The dense fibrotic tissue causes difficulties in wound
      healing and increases the rate of complications. The tubularised incised-plate
      urethroplasty (TIPU) method has become a preferred method for all varieties of
      hypospadias in the past decade. However, fistulas are still one of the most
      common complications of this technique. The aim of this paper was to present the
      preliminary results of TIPU procedure with double de-epithelised dartos flaps in
      failed hypospadias repair. MATERIALS AND METHODS: All patients were treated
      between January 2009 and August 2010 by the same procedure, utilising TIPU with
      double de-epithelised dartos flaps. Vascularised ventral dartos flaps harvested
      from each side of the penis with their vascular supply were transposed to cover
      the suture line by wrapping them from either side of the penis. RESULTS: There
      were 21 boys with failed hypospadias: 20 had previously undergone TIPU, and one
      Koyanagi repair. Patients presented with very large fistulas in four and
      dehiscence in 17. Repair of the failed hypospadias using TIPU with double de
      epithelised dartos flaps was quite successful, with no fistula recurrence or
      dehiscence observed. CONCLUSION: The preliminary results showed that TIPU with
      double de-epithelised dartos flaps is a useful method of successfully repairing
      failed hypospadias.

PMID- 22382098
TI  - Single-stage Modified Duhamel procedure for Hirschsprung's disease : our
      experience.
AB  - INTRODUCTION: Primary single-stage pull-through for Hirschsprung's disease (HD)
      has been reported to give comparable surgical outcomes to staged operations with
      less morbidity. Herein, we present our experience with single-stage Modified
      Duhamel procedure for management of HD. PATIENTS AND METHODS: This was a review
      of 48 cases of HD who underwent single-stage Modified Duhamel procedure without a
      protective colostomy. RESULTS: The age at surgery ranged from 6 months to 10
      years (median - 9 months, mean - 2.3 years). The average weight of the child was
      7.2 kg (range, 4.9-22 kg). 38 (79.2%) patients had classical rectosigmoid HD, the
      rest being long segment HD (the proximal most level being the splenic flexure).
      The average duration of surgery was 175 minutes (range, 130-245 minutes). The
      average blood loss was 45 ml. The average hospital stay was 7.2 days (range: 6-10
      days). The major postoperative complications (n=3) included postoperative
      adhesive intestinal obstruction, anastomotic leak and persistent constipation due
      to residual aganglionosis. Each required a re-exploration. Minor complications
      included surgical site infection (n=3) and post-operative enterocolitis (n=3),
      which were managed conservatively. Six patients had constipation for a limited
      period post-operatively. All patients have a satisfactory functional outcome and
      normal development and growth. CONCLUSIONS: For HD, we recommend that single
      stage Modified Duhamel procedure should be the preferred approach in view of its
      low morbidity, satisfactory functional outcome and avoidance of stoma, multiple
      surgeries and economic benefit in view of decreased hospital stay.

PMID- 22382099
TI  - Gastroschisis: a multi-centre comparison of management and outcome.
AB  - BACKGROUND: Anecdotal evidence and a handful of literature reports suggest that
      the outcome for infants born with gastroschisis in many African countries is poor
      when compared to Western nations. We wished to evaluate current management
      strategies and outcomes in African and Western units that treat infants with
      gastroschisis. PATIENTS AND METHODS: We conducted a retrospective review of case
      notes for infants with gastroschisis who presented to a hospital between 1
      January 2004 and 31 December 2007. There were five participating centres, divided
      for analysis into an African cohort (three centres) and a Western cohort (two
      centres). RESULTS: Fewer infants presented to a hospital with gastroschisis in
      the African cohort when compared to the Western cohort, particularly when the
      size of catchment area of each hospital was taken into account. The physiological
      state of the infant on presentation and management strategy varied widely between
      centres. Primary closure, preformed silo and surgical silo with delayed closure
      were all utilised in the African cohort. Use of the preformed silo and delayed
      abdominal wall closure was the strategy of choice in the Western cohort. The 30
      day mortality was 23% and 1% respectively. This primary outcome measure varied
      considerably in the African cohort but was the same in the two Western units.
      CONCLUSIONS: Gastroschisis in the African cohort was characterised by fewer
      infants presenting to a hospital and a more variable outcome when compared to the
      Western cohort. A detailed epidemiological study to determine the incidence of
      gastroschisis in African countries may provide valuable information. In addition,
      interventions such as prompt resuscitation, safe neonatal transfer, the use of
      the preformed silo and parenteral nutrition could improve outcomes in infants
      with gastroschisis.

PMID- 22382100
TI  - Tube thoracostomy: primary management option for empyema thoracis in children.
AB  - AIM: The aim of this study was to review our experience with tube thoracostomy in
      the management of empyema thoracis in children. PATIENTS AND METHODS: This
      retrospective study included 46 children (26 boys and 20 girls) who were admitted
      and managed for empyema thoracis, between January 1, 2010 and December 31, 2010
      at the author's department of paediatric surgery. RESULTS: During the last 12
      months, 46 children aged below 12 years were treated for empyema thoracis: Five
      (10.86%) were infants, 22 (47.82%) were 1 to 5 years and 19 (41.30%) were 6 to 12
      years of age. All the patients presented with complaints of cough, fever and
      breathlessness of variable durations. Twenty three (50%) children had history of
      pneumonia and treatment prior to development of empyema. Thirty five (76.08%)
      children had right-sided and 11 (23.91%) had left-sided empyema. Thirty nine
      (84.78%) children were successfully treated with tube thoracostomy, systemic
      antibiotics and other supportive measures. Seven (15.21%) children failed to
      respond with above and needed decortications. Most commonly isolated bacteria
      were Pseudomonas (n = 12) and Staphylococcus aureus (n = 7). The average length
      of hospital stay in patients with tube thoracostomy was 15.35 days, and in
      patients who needed decortications was 16.28 days following thoracotomy. There
      was no mortality amongst above treated children. CONCLUSIONS: Majority of
      children with empyema thoracis are manageable with tube thoracostomy,
      antibiotics, physiotherapy and other supportive treatment. Few of them who fail
      to above measures need more aggressive management.

PMID- 22382101
TI  - Feasibility of a simple drainage system in Cameroonian children after thoracotomy
      and decortication for empyema thoracis.
AB  - BACKGROUND: To analyse the outcome of children with empyema thoracis treated by
      decortication followed by a simple drainage system. PATIENTS AND METHODS:
      Retrospective chart review from July 2001 to June 2010 of all cases of children
      who had a thoracotomy for empyema. We used an endotracheal tube as chest drain
      and a urinary bag as a collector. Statistical analyses were done using EXCEL and
      SPSS 9.0. RESULTS: Forty one children underwent thoracotomy and decortication for
      empyema, there were 23 boys and 18 girls with a sex ratio of 1, 21. The mean age
      was 21/2 years with a minimum of 1 month and a maximum of 15 years of age; 27
      children were below two years of age. All the patients have received antibiotic
      for a long period before surgery. The culture was negative, except in two cases
      where we found Klebsiella pneumonia and Staphylococcus aureus. In five cases, the
      empyema was due to Mycobacterium tuberculosis. Three children presented a
      complication: One child had a persistent purulent drainage for 2 weeks; another
      one was re-operated upon because of necrotic lung abscess and one child died of
      sepsis. In most cases, the chest tube was removed between day 4 and day 6 post
      operatively. The average length of hospital stay after the surgery was 10 days.
      CONCLUSION: Thoracotomy and decortication in children with empyema can be safely
      done in Cameroon using a simple drainage system with good results compared to
      those in the literature.

PMID- 22382102
TI  - Ventriculoperitoneal shunt complications needing shunt revision in children: a
      review of 5 years of experience with 48 revisions.
AB  - BACKGROUND: The aim of this study was to review the management of
      ventriculoperitoneal (VP) shunt complications in children. PATIENTS AND METHODS:
      During the last 5 years (January 1, 2006 to December 31, 2010), 236 VP shunt
      operations were performed in children under 12 years of age; of these, 40
      (16.94%) developed shunt complications and those who underwent VP shunt revisions
      were studied. RESULTS: This prospective study included 40 (28 boys and 12 girls)
      children and required 48 shunt revisions. Complications following VP shunts that
      required shunt revisions were peritoneal catheter/peritoneal end malfunction
      (18), shunt/shunt tract infections (7), extrusion of peritoneal catheter through
      anus (5), ventricular catheter malfunction (4), cerebrospinal fluid (CSF) leak
      from abdominal wound (4), shunt system failure (2), ventricular end/shunt
      displacement (2), CSF pseudocysts peritoneal cavity (2), extrusion of peritoneal
      catheter from neck, chest, abdominal scar and through umbilicus, one each. Four
      fifth of these shunt complications occurred within 6 months of previous surgery.
      Surgical procedures done during shunt revisions in order of frequency were
      revision of peritoneal part of shunt (27, 56.25%), revision of entire shunt
      system (6, 12.5%), extra ventricular drainage and delayed re-shunt (5, 10.41%),
      shunt removal and delayed re-shunt (5, 10.41%), opposite side shunting (2,
      4.16%), cysts excision and revision of peritoneal catheter (2, 4.16%) and
      revision of ventricular catheter (1, 2.08%). The mortalities following VP shunt
      operations were 44 (18.64%) and following shunt revisions were 4 (10%).
      CONCLUSIONS: VP shunt done for hydrocephalus in children is not only prone for
      complications and need for revision surgery but also associated with considerable
      mortality.

PMID- 22382103
TI  - Management of postoperative enterocutaneous fistulae in children: a decade
      experience in a single centre.
AB  - BACKGROUND: Enterocutaneous fistula (ECF) in children poses a lot of management
      challenges due to sepsis, malnutrition, fluid and electrolyte deficits, which are
      frequent complications. Knowledge of prognostic factors of postoperative ECF is
      essential for therapeutic decision-making processes. This study examined the
      variables that relate to the outcomes of management of ECF in children. PATIENTS
      AND METHODS: Consecutive children who were managed for postoperative ECF in our
      unit between 2000 and 2009 were evaluated. Data were analysed for clinical
      features, management and its outcome. RESULTS: A total of 54 patients were
      managed for ECF. Majority of the fistulas were due to operation for infective
      causes, with typhoid intestinal perforation ranking the highest. Overall,
      spontaneous closure without operative intervention occurred in 29 (53.7%)
      patients. Twenty-one (38.9%) patients required restorative operations to close
      their fistulas, which was successful only in 12 (22.2%) patients. There was a
      strong correlation between high-output fistulas (jejunal location) and surgical
      closure (P<0.001). Hypoalbuminaemia and jejunal location profoundly resulted in
      non-spontaneous closure of ECF (P<0.001) and were associated with high morbidity
      (P<0.001). Thirteen (24.1%) patients died due to hypokalaemia, sepsis and
      hypoproteinaemia/hypoalbuminaemia. CONCLUSIONS: Majority of the ECF in children
      closed spontaneously following high-protein and high-carbohydrate nutrition.
      Hypoalbuminaemia and jejunal location were important prognostic variables
      resulting in non-spontaneous closure, while hypokalaemia, sepsis and
      hypoproteinaemia/hypoalbuminaemia were associated with high mortality in children
      with ECF.

PMID- 22382104
TI  - Intralesional bleomycin and sodium tetradecyl sulphate for haemangiomas and
      lymphangiomas.
AB  - BACKGROUND: To compare the efficacy of intralesional bleomycin and sodium
      tetradecyl sulphate in treatment of haemangiomas and lymphangiomas. PATIENTS AND
      METHODS: Between July 2007 and May 2009, 120 patients, sixty each of peripheral
      haemangiomas and lymphangiomas, were administered intralesional injection of
      bleomycin in a dose of 0.5-1 U/kg in children less than one year of age and 1 to
      15 units in children more than one year of age and 1 to 3 ml of 2% sodium
      tetradecyl sulphate, depending on the size of the lesion at intervals of 14 days.
      Patients more than 20 years of age and those with diffuse or visceral lesions
      were excluded from the study. RESULTS: Complete resolution occurred in 16
      patients (53%) of haemangiomas and 14 patients (47%) of lymphangiomas treated
      with bleomycin, while the results were 12 patients (40%) and 10 patients (33%),
      respectively, in sodium tetradecyl sulphate group. The satisfactory resolution
      (resolution more than 50%) occurred in eight patients (27%) of haemangiomas and
      lymphangiomas groups treated with bleomycin, while the results were six patients
      (20%) and eight patients (27%), respectively, in sodium tetradecyl sulphate
      group. Poor response rate was observed in six patients (20%) of haemangiomas and
      eight patients (27%) of lymphangiomas of bleomycin group and 12 patients (40%) of
      haemangiomas and lymphangiomas in sodium tetradecyl sulphate group. No pulmonary
      fibrosis or other serious side effects were found. CONCLUSIONS: Intralesional
      bleomycin and sodium tetradecyl sulphate are effective sclerosants in peripheral
      haemangiomas and lymphangiomas, but bleomycin was found to be more efficacious.

PMID- 22382105
TI  - Pre-operative haematological investigations in paediatric orofacial cleft repair:
      any relevance to management outcome?
AB  - AIM AND OBJECTIVES: To determine the value of routine pre-operative haematologic
      investigations in children undergoing orofacial cleft repair. BACKGROUND:
      Although routine pre-operative laboratory screening tests are carried out
      traditionally, some studies suggest that they are not absolutely necessary in the
      management of elective surgical patients. MATERIALS AND METHODS: This is a
      prospective cohort study carried out at a tertiary health facility located in
      Nigeria. A review of the laboratory investigations in 116 paediatric orofacial
      cleft patients undergoing surgery during a 6-year period was undertaken. Pre
      operative laboratory investigations and peri-operative transfusion records were
      analysed for the frequency and impact of abnormal results on treatment plan and
      outcome using the Statistical Packages for the Social Scientists 16.0. RESULTS:
      All the children had pre-operative packed cell volume (PCV) check on admission
      for surgery. The PCV ranged from 23% to 43%, mean was 32.9 (+/-3.7%). Twenty-two
      children (18.6%) had sub-optimal PCV (<30%). Patients with the lowest PCV values
      (23% and 26%) were transfused pre-operatively. The lowest post-operative PCV was
      23%, mean 30.8 (+/-3.3%). There was no occasion of post-operative blood
      transfusion. Eighty-six patients (72.9%) had full or partial serum electrolyte
      and urea analysis. Screening for sickle-cell disease was rarely done. Fourteen
      intra- and post-operative complications were recorded. None of these were
      predictable by the results of pre-operative screening tests carried out. All the
      children were discharged home in satisfactory condition. CONCLUSIONS: Routine
      laboratory testing has minimal impact on management and outcome of orofacial
      cleft surgeries. However, haematocrit screening may be appropriate, particularly
      in clinically pale patients.

PMID- 22382106
TI  - The "diamond port configuration": a standardised laparoscopic technique for
      adolescent intestinal resection and anastomosis.
AB  - BACKGROUND: Familiarity with technique and repetition enhance efficiency during
      laparoscopic surgery. This is particularly important when undertaking complex
      bowel resections. We report a standardised protocol that includes theatre layout,
      patient position and port insertion, which we believe facilitates excellent
      abdominal access and ergonomics and has the potential to shorten the duration of
      the team-learning curve. MATERIALS AND METHODS: A strategic unit development plan
      led to the commencement of a laparoscopic service for adolescents with bowel
      disorders. A standardised protocol for intestinal resections was agreed upon at a
      monthly Paediatric Minimal Access Group meeting. This covered patient position,
      port insertion, technical aspects of intestinal resection and perioperative
      management. In particular, a diamond configuration for ports was agreed upon.
      Data were prospectively collected, and included patient demographics, operative
      times, conversion rates and postoperative outcomes. Unless otherwise indicated,
      data are presented as medians with ranges. RESULTS: Seven procedures were carried
      out in six patients (three female) aged 14 (11-14) years. Access to the entire
      abdominal cavity, vision and ergonomics were excellent in all. There were no
      conversions to open surgery. In all procedures, the technique was considered safe
      and effective. The length of hospital stay was 6.5 (5.8-14) days. CONCLUSION: A
      standardised protocol including the use of the diamond port configuration has
      several putative advantages for laparoscopic bowel resections and anastomoses.
      These include efficiency, reproducibility, predictability, good visibility and
      excellent ergonomics. We recommend this approach as a means to shorten the
      procedure-specific learning curve of the laparoscopic team.

PMID- 22382107
TI  - Generating evidence for surgical practice in Africa: the role of clinical
      research.

PMID- 22382108
TI  - An unusual foreign body in an inguinal hernia sac: case report and literature
      review.
AB  - A 13-month-old boy accidentally ingested a 5 cm dressmaker's pin. On
      presentation, the pin was in the duodenum and there was a right inguinal hernia.
      After 17 days, the pin failed to progress. At surgery, the sac contained appendix
      perforated by the pin. This is the first case in the literature.

PMID- 22382109
TI  - Chylous ascites caused by resection of a choledochal cyst.
AB  - Chylous ascites is a rare complication of abdominal surgery in children.
      Particularly, reports of postoperative chylous ascites are rare. This report
      describes the very rare case of a 10-month-old girl complicated by chylous
      ascites after resection of a choledochal cyst with a Roux-en-Y
      hepaticojejunostomy, who was successfully treated medically. To date, we have
      found a few cases of postoperative chylous ascites in the paediatric literature.
      To the best of our knowledge, this is the first report of chylous ascites after
      the resection of a choledochal cyst in a child who was successfully treated
      solely by no fasting. No fasting might be a therapeutic option of paediatric
      postoperative chylous ascites after the resection of a choledochal cyst if the
      outflow volume of chylous ascites is small.

PMID- 22382110
TI  - Gastric teratoma in a 6-month-old boy.
AB  - Gastric teratomas are very rare embryonal neoplasms, accounting for 2.6% of all
      perinatal diagnosed germ cell tumours. About 85% are well-differentiated mature
      lesions and about 15% are immature tumours with the potential of malignant
      transformation. The recommended therapy for gastric teratomas is surgical
      excision. We present the case of a 6-month-old boy with an incidentally detected
      epigastric mass. The histological examination revealed a mature gastric teratoma.
      The diagnostic imaging, therapy and postoperative follow-up are discussed.

PMID- 22382111
TI  - Idiopathic gastric perforation in an asplenic infant.
AB  - INTRODUCTION: The cause of idiopathic gastric perforations in neonates remains
      unknown. Perforations of the abdominal oesophagus, stomach and duodenum in
      infants and children are the rarest type of intestinal perforations. There are 21
      reported cases of an idiopathic gastric rupture in non-neonates. CASE REPORT: A 6
      week-old boy presented with nausea, vomiting and decreased oral intake. Physical
      examination revealed a firm, distended abdomen tender. Abdominal lateral
      decubitus radiograph revealed massive free air. Patient was found to have an
      idiopathic gastric perforation of the greater curvature with incidental findings
      of asplenia. CONCLUSION: Paediatric abdominal foregut perforations have diverse
      aetiologies. The foregut is the least likely portion of the gastrointestinal
      tract to perforate in children. The aetiology is unknown but there are many
      postulated theories. We present a case of an idiopathic gastric rupture involving
      the greater curvature of 6-week-old boy with incidental findings of being
      asplenic.

PMID- 22382112
TI  - Self-bougienage of oesophageal stricture by an 8-year-old child.
AB  - Oesophageal corrosive injuries have a high potential to result in stricture
      formation with the requirement for repeat oesophageal dilation. Especially in
      children, oesophageal bougienage is performed under general anaesthesia or strong
      sedation. In developing countries without comprehensive medical care, this
      service might not be available. We report the case of daily oesophageal self
      bougienage performed by an 8-year-old Afghan child as highly effective treatment
      of recurrent oesophageal stricture formation after caustic substance ingestion.

PMID- 22382113
TI  - Ruptured liver abscess in a neonate.
AB  - We report a rare case of 17-day-old neonate, diagnosed to have ruptured liver
      abscess secondary to Methicillin-resistant Staphylococcal aureus infection. The
      child presented with septicemia and abdominal distension. On exploration, there
      was pyoperitoneum with ruptured liver abscess.

PMID- 22382114
TI  - Giant bladder diverticulum: a rare cause of bladder outlet obstruction in
      children.
AB  - Giant bladder diverticula are rare causes of bladder outlet obstruction in
      children and have rarely been reported.([1]) In this paper, we present three
      children with giant bladder diverticula who presented with bladder outlet
      obstruction within a year. Micturating cystourethrogram is important for
      investigating bladder outlet obstruction in children and was used to confirm the
      diagnosis in all the patients. The relationship between the diverticula and
      ureters varied, with the ureters running either through the wall of the
      diverticulum and opening directly into the bladder, or opening into the
      diverticulum. In one patient, there was a recurrence, which was excised
      successfully. Excision is important to reduce the risk of recurrence.

PMID- 22382115
TI  - Amyand's like hernia.

PMID- 22382116
TI  - Correction.

PMID- 22382117
TI  - Fibroproliferative changes on high-resolution CT in the acute respiratory
      distress syndrome predict mortality and ventilator dependency: a prospective
      observational cohort study.
AB  - OBJECTIVES: To examine whether the extent of fibroproliferative changes on high
      resolution CT (HRCT) scan influences prognosis, ventilator dependency and the
      associated outcomes in patients with early acute respiratory distress syndrome
      (ARDS). DESIGN: A prospective observational cohort study. SETTING: Intensive care
      unit in a teaching hospital. PARTICIPANTS: 85 patients with ARDS who met American
      European Consensus Conference Criteria and eligible criteria. INTERVENTIONS: HRCT
      scans were performed and prospectively evaluated by two independent observers on
      the day of diagnosis and graded into six findings according to the extent of
      fibroproliferation. An overall HRCT score was obtained by previously published
      method. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was 60-day mortality.
      Secondary outcomes included the number of ventilator-free days, organ failure
      free days, the incidence of barotraumas and the occurrence of ventilator
      associated pneumonia. RESULTS: Higher HRCT scores were associated with
      statistically significant decreases in organ failure-free days as well as
      ventilator-free days. Multivariate Cox proportional hazards model showed that the
      HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI
      1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had
      predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to
      0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08
      to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR
      1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60
      day survival with 71% sensitivity and 72% specificity and of ventilator-weaning
      within 28 days with 75% sensitivity and 76% specificity. CONCLUSIONS: Pulmonary
      fibroproliferation assessed by HRCT in patients with early ARDS predicts
      increased mortality with an increased susceptibility to multiple organ failure,
      including ventilator dependency and its associated outcomes.

PMID- 22382118
TI  - Screening of healthcare workers for tuberculosis: development and validation of a
      new health economic model to inform practice.
AB  - BACKGROUND: Methods for determining cost-effectiveness of different treatments
      are well established, unlike appraisal of non-drug interventions, including novel
      diagnostics and biomarkers. OBJECTIVE: The authors develop and validate a new
      health economic model by comparing cost-effectiveness of tuberculin skin test
      (TST); blood test, interferon-gamma release assay (IGRA) and TST followed by IGRA
      in conditional sequence, in screening healthcare workers for latent or active
      tuberculosis (TB). DESIGN: The authors focus on healthy life years gained as the
      benefit metric, rather than quality-adjusted life years given limited data to
      estimate quality adjustments of life years with TB and complications of
      treatment, like hepatitis. Healthy life years gained refer to the number of TB or
      hepatitis cases avoided and the increase in life expectancy. The authors
      incorporate disease and test parameters informed by systematic meta-analyses and
      clinical practice. Health and economic outcomes of each strategy are modelled as
      a decision tree in Markov chains, representing different health states informed
      by epidemiology. Cost and effectiveness values are generated as the individual is
      cycled through 20 years of the model. Key parameters undergo one-way and Monte
      Carlo probabilistic sensitivity analyses. SETTING: Screening healthcare workers
      in secondary and tertiary care. RESULTS: IGRA is the most effective strategy,
      with incremental costs per healthy life year gained of L10 614-L20 929, base
      case, L8021-L18 348, market costs TST L45, IGRA L90, IGRA specificities of 99%
      97%; mean (5%, 95%), L12 060 (L4137-L38 418) by Monte Carlo analysis.
      CONCLUSIONS: Incremental costs per healthy life year gained, a conservative
      estimate of benefit, are comparable to the L20 000-L30 000 NICE band for IGRA
      alone, across wide differences in disease and test parameters. Health gains
      justify IGRA costs, even if IGRA tests cost three times TST. This health economic
      model offers a powerful tool for appraising non-drug interventions in the market
      and under development.

PMID- 22382120
TI  - Physicians who experience sickness certification as a work environmental problem:
      where do they work and what specific problems do they have? A nationwide survey
      in Sweden.
AB  - OBJECTIVES: In a recent study, 11% of the Swedish physicians below 65 years
      dealing with sickness certification tasks (SCT) experienced SCT to a great extent
      as a work environment problem (WEP). This study aimed at exploring which SCT
      problems those physicians experienced and if these problems varied between
      general practitioners (GPs), psychiatrists, orthopaedists and physicians working
      at other types of clinics. DESIGN: A cross-sectional nationwide questionnaire
      study. SETTING: All physicians working in Sweden in 2008. PARTICIPANTS: The 1554
      physicians <65 years old, working in a clinical setting, having SCT and stating
      SCT to a great extent being a WEP. OUTCOME MEASURES: Frequency of possibly
      problematic situations or lack of time, reasons for sickness certifying
      unnecessarily long, experience of difficulties in contacts with sickness
      insurance offices, and severity of experienced problems. RESULTS: In all, 79% of
      this group of physicians experienced SCT as problematic at least once weekly,
      significantly higher proportion among GPs (p<0.001) and psychiatrists (p=0.005).
      A majority (at most 68.3%) experienced lack of time daily, when handling SCT, the
      proportion being significantly higher among orthopaedists (p=0.003, 0.007 and
      0.011 on three respective items about lack of time). Among psychiatrists, a
      significantly higher proportion (p<0.001) stated wanting a patient coordinator.
      Also, GPs agreed to a higher extent (p<0.001) to finding 14 different SCT tasks
      as 'very problematic'. CONCLUSIONS: The main problem among physicians who
      experience SCT to a great extent as a WEP was lack of time related to SCT. The
      proportion of physicians experiencing problems varied in many aspects
      significantly between the different work clinics; however, GPs were among the
      highest in most types of problems. The results indicate that measures for
      improving physicians' sickness certification practices should be focused on
      organisational as well as professional level and that the needs in these aspects
      differ between specialties.

PMID- 22382119
TI  - Psychosocial consequences of allocation to lung cancer screening: a randomised
      controlled trial.
AB  - OBJECTIVE: To examine the psychosocial consequences of being allocated to the
      control group as compared with the screen group in a randomised lung cancer
      screening trial. METHOD: The Danish Lung Cancer Screening Trial, a randomised
      controlled trial, ran from 2004 to 2010 with the purpose of investigating the
      benefits and harms of lung cancer screening. The participants in Danish Lung
      Cancer Screening Trial were randomised to either the control group or the screen
      group and were asked to complete the questionnaires Consequences Of Screening and
      Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening
      and the COS-LC were used to examine the psychosocial consequences of
      participating in the study, by comparing the control and the screen groups'
      responses at the prevalence and at the incidence round. RESULTS: There was no
      statistically significant difference in socio-demographic characteristics or
      smoking habits between the two groups. Responses to the COS-LC collected before
      the incidence round were statistically significantly different on the scales
      'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and
      'introvert', with the control group reporting higher negative psychosocial
      consequences. Furthermore, the participants in both the control and the screen
      groups exhibited a mean increase in negative psychosocial consequences when their
      responses from the prevalence round were compared with their responses from the
      first incidence round. CONCLUSIONS: Participation in a randomised controlled
      trial on lung cancer screening has negative psychosocial consequences for the
      apparently healthy participants-both the participants in the screen group and the
      control group. This negative impact was greatest for the control group.

PMID- 22382121
TI  - Evidence base for an intervention to maximise uptake of glaucoma testing: a
      theory-based cross-sectional survey.
AB  - OBJECTIVE: To identify factors associated with intention to attend a hypothetical
      eye health test and provide an evidence base for developing an intervention to
      maximise attendance, for use in studies evaluating glaucoma screening programmes.
      DESIGN: Theory-based cross-sectional survey, based on an extended Theory of
      Planned Behaviour (TPB) and the Common Sense Self-Regulation Model, conducted in
      June 2010. PARTICIPANTS: General population including oversampling from low
      socioeconomic areas. SETTING: Aberdeenshire and the London Boroughs of Lewisham
      and Southwark, UK. RESULTS: From 867 questionnaires posted, 327 completed
      questionnaires were returned (38%). In hierarchical regression analysis, the
      three theoretical predictors in the TPB (Attitude, Subjective norm and Perceived
      Behavioural Control) accounted for two-thirds of the variance in intention scores
      (adjusted R(2)=0.65). All three predictors contributed significantly to
      prediction. Adding 'Anticipated regret' as a factor in the TPB model resulted in
      a significant increase in prediction (adjusted R(2)=0.74). In the Common Sense
      Self-Regulation Model, only illness representations about the personal
      consequences of glaucoma (How much do you think glaucoma would affect your life?)
      and illness concern (How concerned are you about getting glaucoma?) significantly
      predicted. The final model explained 75% of the variance in intention scores,
      with ethnicity significantly contributing to prediction. CONCLUSIONS: In this
      population-based sample (including over-representation of lower socioeconomic
      groupings), the main predictors of intention to attend a hypothetical eye health
      test were Attitude, Perceived control over attendance, Anticipated regret if did
      not attend and black ethnicity. This evidence informs the design of a behavioural
      intervention with intervention components targeting low intentions and predicted
      to influence health-related behaviours.

PMID- 22382122
TI  - Should identical CVD risks in young and old patients be managed identically?
      Results from two models.
AB  - OBJECTIVES: To assess whether delaying risk reduction treatment has a different
      impact on potential life years lost in younger compared with older patients at
      the same baseline short-term cardiovascular risk. DESIGN: Modelling based on
      population data. METHODS: Potential years of life lost from a 5-year treatment
      delay were estimated for patients of different ages but with the same
      cardiovascular risk (either 5% or 10% 5-year risk). Two models were used: an age
      based residual life expectancy model and a Markov simulation model. Age-specific
      case fatality rates and time preferences were applied to both models, and
      competing mortality risks were incorporated into the Markov model. RESULTS:
      Younger patients had more potential life years to lose if untreated, but the
      maximum difference between 35 and 85 years was <1 year, when models were
      unadjusted for time preferences or competing risk. When these adjusters were
      included, the maximum difference fell to about 1 month, although the direction
      was reversed with older people having more to lose. CONCLUSIONS: Surprisingly,
      age at onset of treatment has little impact on the likely benefits of
      interventions that reduce cardiovascular risk because of the opposing effects of
      life expectancy, case fatality, time preferences and competing risks. These
      findings challenge the appropriateness of recommendations to use lower risk-based
      treatment thresholds in younger patients.

PMID- 22382123
TI  - Comparison of screening strategies to improve the diagnosis of latent
      tuberculosis infection in the HIV-positive population: a cohort study.
AB  - BACKGROUND: HIV is the most important risk factor for progression of latent
      tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and
      treatment of LTBI is necessary to reduce the increasing burden of TB in the UK,
      but a unified LTBI screening approach has not been adopted. OBJECTIVE: To compare
      the effectiveness of a TB risk-focused approach to LTBI screening in the HIV
      positive population against current UK National Institute for Health and Clinical
      Excellence (NICE) guidance. DESIGN: Prospective cohort study. SETTING: Two urban
      HIV treatment centres in London, UK. PARTICIPANTS: 114 HIV-infected individuals
      with defined TB risk factors were enrolled prospectively as part of ongoing
      studies into HIV and TB co-infection. OUTCOME MEASURES: The yield and case
      detection rate of LTBI cases within the research study were compared with those
      generated by the NICE criteria. RESULTS: 17/114 (14.9%, 95% CI 8.3 to 21.5) had
      evidence of LTBI. Limiting screening to those meeting NICE criteria for the
      general population (n=43) would have detected just over half of these, 9/43
      (20.9%, 95% CI 8.3 to 33.5) and those meeting criteria for HIV co-infection
      (n=74) would only have captured 8/74(10.8%, 95% CI 3.6 to 18.1) cases. The case
      detection rates from the study and NICE approaches were not significantly
      different. LTBI was associated with the presence of multiple TB risk factors
      (p=0.002). CONCLUSION: Adoption of a TB risk-focused screening algorithm that
      does not use CD4 count stratification could prevent more cases of TB
      reactivation, without changing the case detection rate. These findings should be
      used to inform a large-scale study to create unified guidelines.

PMID- 22382124
TI  - Public support for tobacco control policy extensions in Western Australia: a
      cross-sectional study.
AB  - OBJECTIVES: Policy makers seeking to introduce new tobacco control measures need
      to anticipate community support to assist them in planning appropriate
      implementation strategies. This study assessed community support for plain
      packaging and smoking bans in outdoor locations in Australia. DESIGN: Analytical
      cross-sectional survey. SETTING AND PARTICIPANTS: 2005 Western Australian adults
      participated in a computer-assisted telephone interview. Random household
      telephone numbers were used to obtain a representative sample. OUTCOME MEASURES:
      Support for plain packaging of cigarettes and smoking bans at outdoor venues by
      demographic characteristics. RESULTS: Around half of the survey respondents
      supported plain packaging and almost a further quarter reported being neutral on
      the issue. Only one in three smokers disagreed with the introduction of a plain
      packaging policy. A majority of respondents supported smoking bans at five of the
      six nominated venues, with support being strongest among those with children
      under the age of 15 years. The venues with the highest levels of support were
      those where smoke-free policies had already been voluntarily introduced by the
      venue managers, where children were most likely to be in attendance, and that
      were more limited in size. CONCLUSIONS: The study results demonstrate community
      support for new tobacco control policies. This evidence can be used by public
      policy makers in their deliberations relating to the introduction of more
      extensive tobacco control regulations.

PMID- 22382125
TI  - An examination of the path between recent sexual violence and sexually
      transmitted infections.
AB  - PURPOSE: Sexually transmitted infections (STIs) are among the most common
      infections in the United States and are particularly prevalent in survivors of
      sexual violence. The purpose of this study is to examine co-occurring risk
      factors for sexual violence and STIs including mental health, alcohol use, drug
      use, and multiple partners as intersecting pathways to STIs for women who
      experienced sexual abuse in the past year. METHODS: Secondary analyses were
      conducted on cross-sectional data from women originally recruited as respondents
      for an epidemiologic survey funded by the Centers for Disease Control and
      Prevention (CDC): Project CHOICES. The survey was administered to 2,672 women in
      six settings: A large, urban jail and residential alcohol and drug treatment
      facilities (Texas); a gynecology clinic (Virginia); two primary care clinics
      (Virginia and Florida); and media solicitation (Florida). Women were included in
      the current study if they were fertile, sexually active, and not pregnant or
      trying to get pregnant (n = 1,183). Structural equation modeling (SEM) was used
      to test the conceptual path model between sexual violence and STI occurrence.
      RESULTS: In the SEM, there were no significant paths from mental health, alcohol
      severity, or drug use to STI occurrence contrary to the results of the initial
      bivariate analyses. Multiple sexual partners significantly mediated the
      relationship between sexual violence and STIs and between mental health and drug
      use and STIs. CONCLUSION: This study highlights the importance of providing
      effective treatment to survivors of sexual violence, which includes addressing
      risky sexual behaviors to reduce STI occurrence.

PMID- 22382126
TI  - Contextualized stress, global stress, and depression in well-educated, pregnant,
      African-American women.
AB  - PURPOSE: Well-educated, pregnant, African-American women are disproportionately
      at risk for adverse birth outcomes and depression linked to stress has been
      established as a significant contributor to poor birth outcomes. Since racial and
      gendered stress have been identified as threats to birth outcomes, a cross
      sectional study was conducted that utilized the Jackson, Hogue, Phillips
      Contextualized Stress Measure (JHP), a measurement of racial and gendered stress,
      and the Perceived Stress Scale (PSS), an assessment of global stress, to detect
      their associations and predictions for depression as measured by the Beck
      Depression Inventory II (BDI-II). METHOD: We recruited 101 pregnant, well
      educated, African-American women from ob-gyn offices who were administered the
      JHP, the PSS, and the BDI-II. Correlational, chi-square, and stepwise regression
      analyses were conducted with the measures and the demographic variables of
      relationship status, the presence of other children, and annual household income.
      FINDINGS: The results revealed significant linear and covariate associations for
      the JHP, PSS, and BDI-II. Correspondingly, chi-square analysis found significant
      associations for the JHP and the BDI-II and the presence of other children,
      relationship status, and annual household income. Results from the regression
      models found that the contextualized and global stress measures were both
      predictive of depression. Demographic characteristics did not predict depression.
      CONCLUSION: The results argue for prenatal depression and stress screening.
      Furthermore, the link between contextualized stress and depression alerts health
      care providers and local communities to be responsive to the particular stressors
      that pose risks for pregnant African-American women and their babies.

PMID- 22382127
TI  - Quantitative reagent-free detection of fibrinogen levels in human blood plasma
      using Raman spectroscopy.
AB  - Fibrinogen assays are commonly used as part of clinical screening tests to
      investigate haemorrhagic states, for detection of disseminated intravascular
      coagulation and as a predictor of a variety of cardiovascular events. The Clauss
      assay, which measures thrombin clotting time, is the most commonly used method
      for measuring fibrinogen levels. Nevertheless, inconsistencies are present in
      inter-manufacturer reagent sources, calibration standards and methodologies.
      Automated coagulation analysers, which measure changes in optical density during
      the prothrombin time (PT-Fg), have found use in many hospitals. However, the PT
      Fg method is found to give falsely elevated values due to varying choices of
      calibrants, reagents and analysers. As an alternative, Raman spectroscopy has
      previously been applied to the analysis of blood and its various constituents to
      determine various analyte concentrations such as glucose, urea, triglycerides and
      cholesterol. In this study, Raman spectroscopy was investigated for its ability
      to accurately quantify fibrinogen concentration in blood plasma. Samples
      collected from 34 patients were analysed by Raman spectroscopy and the resultant
      spectra were fitted with a Partial Least Squares Regression model using target
      values obtained through a pre-calibrated Clauss fibrinogen assay. Various
      spectral pre-processing methods were utilised to prepare data to be entered into
      a calibration model. A root mean square error of prediction of 0.72 +/- 0.05 g/L
      was achieved with as few as 25 spectra. In this pilot study, Raman spectroscopy
      has been demonstrated to be a robust technique providing rapid and reagent-free
      quantification of fibrinogen levels in blood plasma and a potential alternative
      to the Clauss assay.

PMID- 22382128
TI  - [Analyzing and tracking preoperative and intraoperative astigmatism].
AB  - Precise evaluation of preoperative astigmatism is the first step optimizing
      outcomes. This begins with office-based evaluation of astigmatism; corneal
      astigmatism is evaluated by keratometry, traditionally by Javal keratometry, but
      now including topography, whether Placido- or elevation-based, which allows for
      detailed analysis of even irregular astigmatism, including the corneal periphery,
      which is invaluable. Aberrometers, essentially "super-auto refractors", allow the
      incorporation of additional data into the qualitative analysis of astigmatism.
      The correlation between these multiple preoperative data helps to differentiate
      between corneal and total astigmatism, to infer the lenticular astigmatism, and
      to integrate all of these data into the clinical decision-making process.
      Immediately preoperatively, the 0 and 180 degrees  axes are marked; then, with
      the aid of a special marker, the axis of alignment for the toric IOL is also
      marked. Once the cataract is removed, the toric IOL is injected and pre-aligned;
      the viscoelastic is carefully removed, particularly from between the IOL and
      posterior capsule, with the toric IOL being definitively aligned at this point.
      These alignment techniques represent a major advance, soon to be indispensible
      for toric IOL surgery, which will certainly continue to grow in the future.

PMID- 22382130
TI  - Caffeine in wastewater is a tracer for human fecal contamination.

PMID- 22382129
TI  - New perspectives on the biology of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is a trinucleotide repeat disorder caused by a CGG
      repeat expansion in FMR1, and loss of its protein product FMRP. Recent studies
      have provided increased support for the role of FMRP in translational repression
      via ribosomal stalling and the microRNA pathway. In neurons, particular focus has
      been placed on identifying the signaling pathways such as PI3K and mTOR
      downstream of group 1 metabotropic glutamate receptors (mGluR1/5) that regulate
      FMRP. New evidence also suggests that loss of FMRP causes presynaptic dysfunction
      and abnormal adult neurogenesis. In addition, studies on FXS stem cells
      especially induced pluripotent stem (iPS) cells and new sequencing efforts hold
      out promise for deeper understanding of the silencing process and mutation
      spectrum of FMR1.

PMID- 22382131
TI  - New proangiogenic activity on vascular endothelial cells for C-terminal mechano
      growth factor.
AB  - Angiogenesis is crucial in wound healing. The administration of the C-terminal 24
      a.a. peptide of mechano growth factor (MGF24E) has been previously demonstrated
      to induce more blood vessels in regenerating bone around defective areas compared
      with the control. Accordingly, this study aims to determine whether MGF24E
      promotes bone defect healing through MGF24E-increased angiogenesis and whether
      MGF24E has positive effects on angiogenesis in vitro. The roles of MGF24E on
      angiogenesis and the underlying mechanisms were investigated. The cell
      proliferation, migration, and tubulogenesis of the human vascular endothelial
      EA.hy926 cells co-treated with 2% serum and MGF24E were determined to assess
      angiogenesis in comparison with 100 ng/ml of vascular endothelial growth factor
      165 (VEGF(165))-positive control or vehicle control (phosphate-buffered saline).
      MGF24E treatment (10 ng/ml) significantly promoted the biological processes of
      angiogenesis on EA.hy926 cells compared with the vehicle control. The suppression
      of vascular endothelial growth factor and angiopoietin-I expressions by 2% serum
      starvation was reversed by the addition of 10 ng/ml of MGF24E in 2% serum medium.
      This result suggests that MGF24E has a protective effect on angiogenesis.
      Moreover, the inhibition of ERK due to PD98050 pretreatment completely abolished
      and mostly blocked MGF24E-induced proliferation and migration, respectively,
      whereas the MGF24-induced tubulogenesis and the angiogenic factor expression were
      only partially inhibited. These new findings suggest that MGF24E promotes
      angiogenesis by enhancing the expression of angiogenic cytokines which involves
      the MAPK/ERK-signaling pathway.

PMID- 22382132
TI  - Windows to the soul: children and adults see the eyes as the location of the
      self.
AB  - Where are we? In three experiments, we explore preschoolers' and adults'
      intuitions about the location of the self using a novel method that asks when an
      object is closet to a person. Children and adults judge objects near a person's
      eyes to be closer to her than objects near other parts of her body. This holds
      even when considering an alien character whose eyes are located on its chest.
      Objects located near the eyes but out of sight are also judged to be close,
      suggesting that participants are not using what a person can see as a proxy for
      what is close to her. These findings suggest that children and adults intuitively
      think of the self as occupying a precise location within the body, at or near the
      eyes.

PMID- 22382133
TI  - Synthesis, reactivity and applications of zinc-zinc bonded complexes.
AB  - The discovery of decamethyldizincocene [Zn(2)(eta(5)-Cp*)(2)] (Cp* = C(5)Me(5)),
      the first complex containing a covalent zinc-zinc bond, by Carmona in 2004
      initiated the search for this remarkable class of compounds. Low-valent
      organozinc complexes can either be formed by ligand substitution reactions of
      [Zn(2)(eta(5)-Cp*)(2)] or by reductive coupling reactions of Zn(ii) compounds. To
      the best of our knowledge, until now 25 low-valent Zn-Zn bonded molecular
      compounds stabilized by a variety of sterically demanding, very often chelating,
      organic ligands have been synthesized and characterized. There are two major
      reaction pathways of [Zn(2)(eta(5)-Cp*)(2)]: it can either react with cleavage of
      the Zn-Zn bond or by ligand substitution. In addition, upon reaction with late
      transition metal complexes, [Zn(2)(eta(5)-Cp*)(2)] was found to form novel
      intermetallic complexes with Cp*Zn and Cp*Zn(2) acting as unusual one-electron
      donor ligands. Very recently, the potential capability of [Zn(2)(eta(5)-Cp*)(2)]
      to serve as a suitable catalyst in hydroamination reactions was demonstrated.
      Finally, the recent work on Cd-Cd bonded coordination compounds is reviewed.

PMID- 22382134
TI  - Decreased c-Jun expression correlates with impaired spinal motoneuron
      regeneration in aged mice following sciatic nerve crush.
AB  - Post-injury nerve regeneration of the peripheral nervous system declines with
      age, but the mechanisms underlying the weakened axonal regeneration are not well
      understood. Increased synthesis and activity of the AP-1 transcription factor c
      Jun have been implicated in efficient motor axonal regeneration. In the present
      study, we evaluated the hypothesis that the impaired regenerative capacity in the
      aged is associated with impaired induction of c-Jun. In non-manipulated young
      adult or aged mice, no c-Jun and its phosphorylated form were detected in the
      ventral horn of the spinal cord. Following nerve crush, significant c-Jun and
      phosphorylated c-Jun occurred in the injured motoneurons of young adult mice, but
      not in aged animals. In accord with the immunohistochemistry, Western blots also
      showed that sciatic nerve crush induced c-Jun and its phosphorylation expression
      in the ventral horn of young adult but not in aged mice. Changes in c-Jun mRNA
      level detected by in situ hybridization are congruent with that in c-Jun protein
      content, showing an increase at 5 days after crush in young adult but not aged.
      Moreover, compared with young adult mice, aged mice showed impaired motor axonal
      regeneration. These results demonstrate that the impaired motor axonal
      regeneration seen in aged mice is correlated with impaired c-Jun expression and
      phosphorylation following injury. These data provide a neurobiological
      explanation for the poor outcome associated with nerve repair in the aged.

PMID- 22382135
TI  - How to cope when becoming paralysed.

PMID- 22382136
TI  - [Atrial fibrillation : new anticoagulants and antiarrhythmic drugs].
AB  - Atrial fibrillation is the most common form of arrhythmia and one of the most
      frequent causes of ischemic stroke. Several new anticoagulants have recently been
      introduced as alternatives to vitamin-K antagonists for prophylaxis of ischemic
      stroke and tested in phase-3 studies for efficacy and safety. Identifying
      patients who will profit in particular from the new anticoagulant therapy is
      crucial to the clinical application of these drugs. Vernakalant and dronedarone
      are new antiarrhythmic drugs for rhythm control of atrial fibrillation. However,
      therapeutic efficacy of the new agents still has to be proven.

PMID- 22382137
TI  - [Interventional electrophysiology in cardiac MRI : what is the current status?].
AB  - The ablation of simple and complex cardiac arrhythmias has become a first-line
      therapy in interventional cardiology and is mainly guided by conventional
      fluoroscopy. Cardiac magnetic resonance imaging (cMRI) allows exact three
      dimensional (3D) visualization of complex anatomical structures and serves in the
      planning and implementation of ablation procedures. Post-procedural lesion
      visualization using cMRI can assess the success of ablation therapy and may
      distinguish potential complications. Performing ablation directly in the MRI
      scanner, with the option of anatomical substrate imagining, exact catheter
      navigation and real-time lesion visualization, holds the promise of improving
      success rates and safety in the interventional therapy of simple and complex
      arrhythmias.

PMID- 22382138
TI  - [Coronary intervention. 2012 update].
AB  - In-stent restenosis and stent thrombosis are still the main topics of any update
      on coronary intervention. One of the challenging issues in the past year lay in
      answering the question of whether the data on first-generation drug-eluting
      stents are still relevant in the light of newer stent designs and drugs. Other
      issues include new strategies in antiplatelet therapy, treatment of in-stent
      restenosis, particularly drug-eluting stent restenosis, treatment of multivessel
      and left-main disease, as well as the latest developments in bioresorbable
      polymers and "scaffolds". In the light of demographic changes, the main challenge
      for the interventional community is to build an evidence base for the adequate
      treatment of elderly patients in order to resolve uncertainties in the treatment
      of this challenging patient group.

PMID- 22382139
TI  - Cryoballoon in atrial fibrillation ablation.
AB  - Encouraging results of ablation therapy in patients with paroxysmal atrial
      fibrillation (AF) have prompted changes in professional practice guidelines. The
      most recent European guidelines have suggested that ablation might be offered as
      first-line therapy in selected patients. Cryoballoon ablation is a promising
      technology in interventional AF therapy. Two different sizes of the cryoballoon
      are currently available: a smaller (23 mm) and a larger (28 mm) balloon relative
      to the ostial diameter of the pulmonary veins. New tools, the circular mapping
      catheter and the use of intracardiac echocardiography, provide important
      periprocedural information. A meta-analysis of previous studies revealed outcome
      data with an AF-free survival rate of 72.83% at the 1-year follow-up in
      paroxysmal AF patients undergoing cryoballoon ablation. The most frequent, but
      reversible complication is phrenic nerve palsy with reported incidences up to
      10%. All efforts must be taken to overcome this limitation, since the overall
      major complication rate tends to be lower in cryoballoon compared to
      radiofrequency ablation. In persistent AF, reported results in cryoballoon
      ablation had a limited success rate below 50% after a single procedure. A double
      balloon approach using both cryoballoon sizes might overcome some of the
      limitations in persistent AF. Prospective data and randomized studies are
      required. This article outlines the current status of cryoballoon technology in
      AF ablation therapy.

PMID- 22382140
TI  - [Molecular mechanisms of atrial fibrillation: potential role of microRNAs as new
      therapeutic targets and potential biomarkers].
AB  - Atrial fibrillation represents the most common form of clinical arrhythmia in
      daily routine. However, current therapeutic options are still limited and a
      better understanding of the underlying molecular mechanisms is expected to
      contribute to the development of new therapeutic strategies. The scientific field
      of microRNA research has received a lot of attention in recent years, especially
      regarding cardiovascular research. This article gives a brief overview of the
      most recent developments in microRNA research in the field of atrial fibrillation
      and atrial remodelling processes. Furthermore, the clinical perspective of
      microRNAs as new therapeutic targets and as potential biomarkers is discussed.

PMID- 22382141
TI  - [Interventional cardiovascular therapy. Current status 2012].

PMID- 22382142
TI  - Effect of age on immunological response in the first year of antiretroviral
      therapy in HIV-1-infected adults in West Africa.
AB  - OBJECTIVE: To assess the effect of aging on the immunological response to
      antiretroviral therapy (ART) in the West African context. METHODS: The change in
      CD4 T-cell count was analysed according to age at the time of ART initiation
      among HIV-infected patients enrolled in the International epidemiological
      Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4
      gain over 12 months of ART was estimated using linear mixed models. Models were
      adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar
      period and ART regimen. RESULTS: The total number of patients included was
      24,107, contributing for 50,893 measures of CD4 cell count in the first year of
      ART. The baseline median CD4 cell count was 144 cells/MUl [interquartile range
      (IQR) 61-235]; median CD4 cell count reached 310 cells/MUl (IQR 204-443) after 1
      year of ART. The median age at treatment initiation was 36.3 years (10th-90th
      percentiles = 26.5-50.1). In adjusted analysis, the mean CD4 gain was
      significantly higher in younger patients (P < 0.0001). At 12 months, patients
      below 30 years recovered an additional 22 cells/MUl on average [95% confidence
      interval (CI) 2-43] compared to patients at least 50 years. CONCLUSION: Among HIV
      infected adults in West Africa, the immunological response after 12 months of ART
      was significantly poorer in elderly patients. As the population of treated
      patients is likely to get older, the impact of this age effect on immunological
      response to ART may increase over time.

PMID- 22382143
TI  - Comparing different measures of retention in outpatient HIV care.
AB  - OBJECTIVES: The US National HIV/AIDS Strategy identifies retention in care as an
      important quality performance measure. There is no gold standard to measure
      retention in care. This study is the first to compare different measures of
      retention, using a large geographically diverse sample. DESIGN: A prospective
      cohort of 17,425 HIV-infected adults enrolled in care at 12 US HIV clinics
      between 2001 and 2008. METHODS: We compared three measures of retention for each
      patient: proportion of time not spent in a gap of more than 6 months between
      successive outpatient visits; proportion of 91-day quarters in which at least one
      visit occurred; proportion of years in which two or more visits separated by at
      least 90 days occurred. Associations among measures and effects of
      sociodemographic and clinical characteristics were examined. RESULTS: The three
      measures of retention were moderately to strongly correlated. Averaging across
      patients, 71% of time in care was not spent in a gap more than 6 months; 73% of
      all quarters had at least one visit; and 75% of all years had at least two visits
      separated by at least 90 days. For all measures, retention was significantly
      higher for women, whites, older individuals, men who had sex with men (MSM)
      related HIV transmission, and initial CD4 cell counts 50 cell/MUl or less.
      CONCLUSIONS: This is one of the first studies to provide a national estimate of
      retention in HIV care in the US, which ranged from 71 to 75% using any of the
      accepted retention measures. Future studies should assess how well different
      measures predict clinical outcomes and establish acceptable target levels for
      retention.

PMID- 22382144
TI  - LDLr genotype modifies the impact of IL28B on HCV viral kinetics after the first
      weeks of treatment with PEG-IFN/RBV in HIV/HCV patients.
AB  - OBJECTIVE: To evaluate the effect of low-density lipoprotein receptor (LDLr) and
      IL28B genotypes on hepatitis C virus (HCV) viral kinetics in the first 4 weeks of
      treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) in HIV patients co
      infected with HCV genotype 1. METHODS: HIV patients co-infected with HCV genotype
      1 and naive to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV
      RNA viral loads were measured at baseline and at weeks 1, 2 and 4 after start of
      therapy. Differences in viral load decline were evaluated for IL28B (CC versus
      non-CC) and LDLr (CC versus non-CC) genotypes between baseline and weeks 1, 2 and
      4. Additionally, the effect of LDLr genotype on HCV viral decline in IL28B CC
      genotype patients (CC/CC versus CC/non-CC) was analyzed. RESULTS: Eighty-seven
      HIV/HCV genotype 1 co-infected patients were included in the study. Patients
      carrying the LDLr-CC or IL28B-CC genotypes showed greater HCV viral decline than
      those with IL28B non-CC or LDLr non-CC genotypes at every time-point analyzed.
      CC/CC patients had higher rapid virological response (RVR) rates than CC/non-CC
      patients (41.2 versus 13.3%; P < 0.001). Moreover, at all time points, the CC/CC
      pattern was associated with greater HCV viral decline than the CC/non-CC genotype
      (week 1: 1.18 +/- 0.51 versus 0.31 +/- 0.29, P = 0.041; week 2: 1.55 +/- 0.81
      versus 0.93 +/- 0.73, P = 0.032; week 4: 2.23 +/- 1.1 versus 1.5 +/- 0.94, P =
      0.039). CONCLUSION: The LDLr genotype impacts on viral kinetics during the first
      days of starting treatment with PEG-IFN/RBV in HIV/HCV genotype 1 co-infected
      patients, and modifies the impact of IL28B on HCV viral decay.

PMID- 22382145
TI  - The role of microRNAs in HIV-1 pathogenesis and therapy.
AB  - There has been a paradigm shift in our understanding of how protein regulation
      occurs within mammalian cells in the last 15 years. Our current understanding is
      that small, noncoding RNA molecules called microRNAs (miRNAs) play a vital role
      in modulating the translation of mRNAs into protein. Important studies suggest
      that HIV-1 replication may be restricted by certain host cellular miRNAs, and
      this in turn may play pivotal roles in host defense and in maintaining latency
      within resting CD4 T cells. Conversely, host cellular miRNAs have also been
      demonstrated to be essential for certain viruses to establish infection and the
      altered expression of cellular miRNAs in the setting of HIV-1 may also be a
      factor favoring viral replication. The differential expression of important
      protective histocompatability locus antigen (HLA) alleles in HIV-1 infection has
      recently been shown to be regulated by miRNAs. To date, most efforts into finding
      an effective vaccine to combat HIV-1 have not been successful. Understanding the
      role that miRNAs may play in HIV-1 pathogenesis may allow a different approach to
      targeting key small RNAs or the identification of new important protein targets
      regulated by miRNAs, which may result in a better vaccine construct. The purpose
      of this review is to look at our current state of understanding of how HIV-1 and
      the miRNA pathway interact and the possible therapeutic interventions that this
      knowledge may entail.

PMID- 22382146
TI  - Detection of HIV-1 RNA in seminal plasma samples from treated patients with
      undetectable HIV-1 RNA in blood plasma on a 2002-2011 survey.
AB  - OBJECTIVES: To estimate the frequency of detectable seminal HIV-1 viral load in
      men with repeatedly undetectable blood viral load, in the recent past years and
      over a 10-year period (2002-2011) in a large cohort of HIV-1-infected men from
      couples requesting assisted reproduction technologies. We also searched for an
      association between HIV-1 RNA seminal viral load, HIV-1 RNA plasma viral load
      measured by ultrasensitive assay, and blood HIV-1 DNA in a subgroup of 98
      patients. METHODS: Three hundred and four HIV-1 infected men have provided 628
      paired blood and semen samples. In a subset of 98 patients for which a blood
      sample was available, residual viremia, HIV-1 RNA in semen and HIV-1 DNA were
      studied. RESULTS: Twenty of 304 patients (6.6%) had detectable HIV-1 RNA in
      semen, ranging from 135 to 2365 copies/ml, corresponding to 23 samples, although
      they had concomitantly undetectable HIV-1 RNA in blood while they were under
      antiretroviral therapy. This prevalence was stable over time even in recent
      years. There was an association between HIV-1 RNA plasma viral load measured by
      ultrasensitive assay and HIV-1 DNA in blood, but both were not associated with
      seminal HIV-1 RNA viral load. CONCLUSION: It seems cautious individually to
      maintain the recommendations of safe sex and the recourse to ART, or at least to
      inform the couple of the residual potential risk, in serodiscordant couples
      desiring a child.

PMID- 22382147
TI  - The association of CD4+ T-cell counts and cardiovascular risk in treated HIV
      disease.
AB  - OBJECTIVE: HIV-infected individuals are at high risk of developing cardiovascular
      disease. Whether earlier initiation of HIV therapy at higher CD4 cell counts has
      any effect on cardiovascular risk as assessed by endothelial function is unknown.
      DESIGN: Cross-sectional study of 74 antiretroviral-treated men with undetectable
      plasma HIV RNA levels. METHODS: Participants underwent noninvasive assessment of
      endothelial function using brachial artery flow-mediated dilation (FMD). The
      association of nadir and current CD4 T-cell count with FMD was assessed using
      multivariable linear regression. RESULTS: The median age was 47 years
      [interquartile range (IQR) 42-55], median current CD4 T-cell count was 659
      cells/MUl (IQR 542-845), and nadir CD4 cell count was 314 cells/MUl (IQR 150
      490). Twenty-eight percent had hypertension, and 32% hyperlipidemia. Nadir CD4 T
      cell count less than 350 cells/MUl was associated with lower FMD in age-adjusted
      and race-adjusted analyses and remained an independent predictor of FMD after
      adjustment for cardiovascular risk factors (hypertension, diabetes, smoking,
      hyperlipidemia) and HIV-related characteristics (HIV duration, HAART duration).
      After multivariable adjustment, individuals with nadir CD4 T-cell count less than
      350 cells/MUl had a 1.22% lower FMD compared with those with higher T-cell counts
      [95% confidence interval (CI) -2.20 to -0.19, P=0.02]. Proximal CD4 T-cell count
      showed little association with FMD. CONCLUSION: Among treated HIV-infected
      individuals, nadir CD4 T-cell count less than 350 cells/MUl is independently
      associated with lower FMD, suggesting that delayed therapy results in sustained
      harm to endothelial function. Our data support future prospective studies
      evaluating cardiovascular effects of HAART initiation at higher CD4 cell counts.

PMID- 22382148
TI  - T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected
      children.
AB  - OBJECTIVE: To evaluate baseline T-cell activation and neurodevelopmental outcomes
      over time in a cohort of perinatally HIV-infected (PHIV-infected) children with
      severe disease. DESIGN: Pediatric AIDS Clinical Trials Group protocol 366 (PACTG
      366) was a partially randomized, open-label, multicenter 96-week antiretroviral
      treatment-algorithm study. Neurodevelopmental status, measured by age-dependent
      evaluations (Bayley scales of infant development-II; Wechsler preschool and
      primary scale of intelligence-revised; Wechsler intelligence scale for children
      III), was a secondary outcome. METHODS: Linear mixed models were used to assess
      the baseline and follow-up neurodevelopmental outcomes in relation to immune
      activation, measured by CD38 and human leukocyte antigen (HLA) DR expression on
      peripheral CD4(+) and CD8(+) T cells at study baseline. Models were adjusted for
      age, sex, race/ethnicity, baseline viral load, baseline CD4%, cytomegalovirus
      (CMV) infection status at entry, study treatment arms, central nervous system
      penetrance score of antiretroviral regimen at entry, and viral load response 16
      weeks postentry. RESULTS: Among 126 PACTG 366 enrollees who were at least 1 year
      old and had both immune activation and age-appropriate neurodevelopmental
      assessments at baseline, 80 (63%) were black non-Hispanic, 71 (56%) males, 122
      (97%) were on antiretrovirals, and 45 (36%) were in Centers for Disease Control
      and Prevention (CDC) disease category C at entry. CD4(+)CD38(+)HLADR(+)%,
      CD4(+)CD38(-)HLADR(+)%, and CD8(+)CD38(+)HLADR(+)% were positively associated
      with full-scale Intelligence Quotient scores (FSIQ) (slope = 0.18, 0.70, and
      0.15, respectively; P = 0.02, 0.03, and 0.04, respectively). CD4(+)CD38(+)HLADR(
      )% was negatively associated with FSIQ (slope =  -0.16, P = 0.01). CONCLUSION:
      Contrary to HIV-infected adults, in PHIV-infected children higher
      CD4(+)CD38(+)HLADR(+)% may be associated with a neuroprotective effect and higher
      percentage of CD4(+)CD38(+) but HLADR(-) T cells may be deleterious.

PMID- 22382149
TI  - Recovery of HIV service provision post-earthquake.
AB  - OBJECTIVE: To describe the level of functionality of President's Emergency Plan
      for AIDS Relief (PEPFAR)-supported HIV clinical services following the
      devastating earthquake that struck Haiti in January 2010. DESIGN: Available
      program-monitoring data from sites providing voluntary counseling and testing for
      HIV (VCT), antenatal care (ANC) and prevention of mother-to-child transmission
      (PMTCT) services, and antiretroviral treatment (ART) were described, comparing
      pre-earthquake and post-earthquake periods during October 2008 to May 2010.
      METHODS: Pre-earthquake HIV service baselines for VCT, PMTCT, and ART enrollment
      were defined as monthly mean total number of patients served over 15 months pre
      earthquake. ART baseline was defined as total current patients by December 2009.
      Sites were categorized as high-earthquake or low-earthquake intensity based on
      location and instrumental shake intensity data. RESULTS: Pre-earthquake mean
      monthly baselines were 41 087 (VCT), 11 909 (HIV testing at ANC sites), 648 (ART
      enrollment), and 296 (PMTCT enrollment); baseline total current patients on ART
      was 24 863. Service provision in January and May 2010, reported as percentage of
      baseline, was 43 and 78.7% (VCT), 50.8 and 88.7% (HIV testing at ANC), 46 and 81%
      (PMTCT), and 41 and 82.7% (ART enrollment), respectively. Current patients on ART
      decreased to 97% of baseline in April, rising to 103.9% by May; the initial
      decline was restricted to high-earthquake intensity areas. CONCLUSION: Following
      the Haiti earthquake, there was a transient, marked decline in VCT and new ART
      patient enrollment, whereas follow-up of established ART patients remained
      impressively high. HIV treatment continuity should be reinforced in disaster
      preparedness and response strategies in HIV epidemic settings.

PMID- 22382150
TI  - Circumcision status and incident herpes simplex virus type 2 infection, genital
      ulcer disease, and HIV infection.
AB  - OBJECTIVE: We assessed the protective effect of medical male circumcision (MMC)
      against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD)
      incidence. DESIGN: Two thousand, seven hundred and eighty-seven men aged 18-24
      years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or
      delayed circumcision (n=1393) and assessed by HIV and HSV-2 testing and medical
      examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. METHODS: Cox
      regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2)
      for circumcision status and multivariable models estimated HIV risk associated
      with HSV-2, GUD, and circumcision status as time-varying covariates. RESULTS: HIV
      incidence was 1.42 per 100 person-years. Circumcision was 62% protective against
      HIV [risk ratio=0.38; 95% confidence interval (CI) 0.22-0.67] and did not change
      when controlling for HSV-2 and GUD (risk ratio=0.39; 95% CI 0.23-0.69). GUD
      incidence was halved among circumcised men (risk ratio=0.52; 95% CI 0.37-0.73).
      HSV-2 incidence did not differ by circumcision status (risk ratio=0.94; 95% CI
      0.70-1.25). In the multivariable model, HIV seroconversions were tripled (risk
      ratio=3.44; 95% CI 1.52-7.80) among men with incident HSV-2 and seven times
      greater (risk ratio=6.98; 95% CI 3.50-13.9) for men with GUD. CONCLUSION:
      Contrary to findings from the South African and Ugandan trials, the protective
      effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect
      on HSV-2 incidence. Determining the causes of GUD is necessary to reduce
      associated HIV risk and to understand how circumcision confers protection against
      GUD and HIV.

PMID- 22382152
TI  - HIV as an independent risk factor for incident lung cancer.
AB  - BACKGROUND: It is unclear whether the elevated rate of lung cancer among HIV
      infected persons is due to biological effects of HIV, surveillance bias, or
      excess smoking. We compared the incidence of lung cancer between HIV-infected and
      demographically similar HIV-uninfected patients, accounting for smoking and stage
      of lung cancer at diagnosis. DESIGN: Data from the Veterans Aging Cohort Study
      Virtual Cohort were linked to data from the Veterans Affairs Central Cancer
      Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and
      75,750 uninfected patients. METHODS: We calculated incidence rates of
      pathologically confirmed lung cancer by dividing numbers of cases by numbers of
      person-years at risk. We used Poisson regression to determine incidence rate
      ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence,
      previous bacterial pneumonia, and chronic obstructive pulmonary disease. RESULTS:
      The incidence rate of lung cancer in HIV-infected patients was 204 cases per
      100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected
      patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung
      cancer associated with HIV infection remained significant after multivariable
      adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not
      differ between HIV-infected and uninfected patients. CONCLUSION: In our cohort of
      demographically similar HIV-infected and uninfected patients, HIV infection was
      an independent risk factor for lung cancer after controlling for potential
      confounders including smoking. The similar stage distribution between the two
      groups indicated that surveillance bias was an unlikely explanation for this
      finding.

PMID- 22382151
TI  - Safety of tenofovir use during pregnancy:  early growth outcomes in HIV-exposed
      uninfected infants.
AB  - OBJECTIVE: To evaluate the association of tenofovir disoproxil fumarate (TDF) use
      during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU)
      infants. DESIGN: US-based prospective cohort study of HEU children to examine
      potential adverse effects of prenatal TDF exposure. METHODS: We evaluated the
      association of maternal TDF use during pregnancy with small for gestational age
      (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for
      age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn
      visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW
      and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted
      linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF
      exposure. RESULTS: Of 2029 enrolled children with maternal antiretroviral
      information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14%
      in 2003 to 43% in 2010. There was no difference between those exposed to
      combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ.
      However, at age 1 year, infants exposed to combination regimens with TDF had
      significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17
      vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02). CONCLUSION: TDF use during
      pregnancy was not associated with increased risk for LBW or SGA. The slightly
      lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of
      uncertain significance but underscore the need for additional studies of growth
      outcomes after TDF use during pregnancy.

PMID- 22382153
TI  - Letter by Powers Regarding Article, "Failure of cerebral hemodynamic selection in
      general or of specific positron emission tomography methodology? Carotid
      occlusion surgery study (COSS)".

PMID- 22382154
TI  - High levels of S100A12 are associated with recent plaque symptomatology in
      patients with carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is a progressive chronic disease, in
      which inflammation plays a key role. The calcium-binding proteins calgranulins
      including S100A8, S100A9, and S100A12 are involved in many cellular activities
      and pathological processes including inflammation. We therefore hypothesized that
      calgranulins may be markers of plaque instability in patients with carotid
      atherosclerosis. METHODS: Plasma levels of S100A8/A9 and S100A10 were measured in
      159 consecutive patients with high-grade carotid stenosis and in 22 healthy
      control subjects. The mRNA levels of calgranulins were also measured within the
      atherosclerotic carotid plaques, and their regulation was analyzed in vitro in
      monocytes. RESULTS: Our main findings were: (1) plasma levels of S100A12 were
      significantly higher in patients with carotid atherosclerosis compared with
      healthy control subjects with the highest levels in patients with the most recent
      symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a
      modest increase in patients with symptoms in the previous 2 to 6 months but not
      in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed
      increased expression in atherosclerotic carotid plaques from patients with the
      most recent symptoms compared with the remaining patients; (4) in THP-1
      monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of
      S100A8, S100A9, and S10012 and interleukin-1beta, interferon gamma, and releasate
      from thrombin-activated platelets significantly enhanced the expression of
      S100A12. CONCLUSIONS: Our findings support a link between calgranulins and
      atherogenesis and suggest that these mediators, and in particular S100A12, may be
      related to plaque instability.

PMID- 22382155
TI  - Factors affecting clot lysis rates in patients with spontaneous intraventricular
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: In the treatment of severe intraventricular hemorrhage
      (IVH), thrombolytic use and clot size are known to influence clot lysis rates. We
      evaluated the effect of other variables on IVH clot lysis rates among patients
      treated with recombinant tissue-type plasminogen activator or placebo. METHODS:
      One hundred patients with IVH and intracerebral hemorrhage volume <30 mL
      requiring emergency external ventricular drainage from 2 multicenter trials were
      treated with intraventricular administration of recombinant tissue-type
      plasminogen activator (n=78; 53 males, 25 females) or placebo (n=22; 7 males, 15
      females). IVH volume was quantified daily by head CT. A segmented linear
      regression using an optimized spline knot for each patient was fit. Random
      effects linear regression was used to estimate the effect of prespecified patient
      characteristics on clot lysis rates over the first 6 days. RESULTS: Stability IVH
      volumes were larger in males (N=60; 54 +/- 5 mL) than females (N=40; 36 +/- 5 mL;
      P=0.01). Intraventricular thrombolytic treatment was associated with an increase
      in clot lysis rate of 14.6% of stability IVH volume/day before the spline knot
      compared with the placebo group (P<0.001). After adjustment for thrombolytic,
      higher baseline serum plasminogen and lower baseline platelet count were
      independently associated with an increase in clot lysis of 1.28%/day per 10-g/dL
      increase (P<0.001) and 0.70% /day per 10*10(3)/uL decrease (P<0.001) before the
      knot, respectively. CONCLUSIONS: Although thrombolysis remains the major
      determinant of IVH clot lysis rate, higher baseline serum plasminogen and lower
      platelet count also predict faster clot lysis. Further studies are needed to
      confirm whether plasminogen availability and thrombus structure impact IVH clot
      removal. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique
      identifier: NCT00650858.

PMID- 22382156
TI  - Manual aspiration thrombectomy: adjunctive endovascular recanalization technique
      in acute stroke interventions.
AB  - BACKGROUND AND PURPOSE: We evaluated recanalization rates, clinical outcomes, and
      safety when manual aspiration thrombectomy is used in conjunction with other
      thrombolytic modalities in a consecutive case series of patients with large
      vessel intracranial occlusion. METHODS: We conducted a retrospective review of a
      prospectively acquired acute endovascular stroke database. Manual aspiration
      thrombectomy was carried out with Distal Access and Penumbra reperfusion
      catheters of different sizes placed in the thrombus and aspirated with a syringe.
      RESULTS: We identified 191 patients: Occlusion locations were as follows: M1% to
      50%, M2% to 10%, internal carotid artery terminus 25%, and vertebrobasilar 15%.
      Median treatment duration was 90 minutes. Recanalization results were
      Thrombolysis in Myocardial Ischemia 2/3 93%, Thrombolysis in Myocardial Ischemia
      3 27%, Thrombolysis In Cerebral Infarction 2a/2b/3 91%, Thrombolysis In Cerebral
      Infarction 2b/3 71%, and Thrombolysis In Cerebral Infarction 3 25%. Larger
      catheters were associated with higher recanalization rates. Parenchymal hematoma
      rate was 13.6%. The favorable outcome (90-day modified Rankin Scale <= 2) rate
      was 54%. Mortality at 90 days was 25%. CONCLUSIONS: Manual aspiration
      thrombectomy is a useful addition to the armamentarium of endovascular treatment
      modalities for acute stroke.

PMID- 22382157
TI  - Fibrin D-dimer, tissue-type plasminogen activator, von Willebrand factor, and
      risk of incident stroke in older men.
AB  - BACKGROUND AND PURPOSE: Abnormalities in blood coagulation and the fibrinolytic
      system have been associated with increased risk of stroke, but few prospective
      studies have studied the associations in older adults. We have examined the
      associations between fibrin D-dimer, tissue-type plasminogen activator, and von
      Willebrand factor (vWF) and risk of stroke in older men and examined their
      predictive roles separately in normotensive and hypertensive men. METHODS:
      Prospective study of 3358 men aged 60 to 79 years with no previous diagnosis of
      myocardial infarction or stroke and without atrial fibrillation followed-up for
      an average of 9 years, during which there were 187 incident stroke events.
      RESULTS: Increased levels of D-dimer and vWF were associated with significantly
      increased risk of major stroke events after adjustment for potential confounders,
      including systolic blood pressure (adjusted hazard ratios and 95% confidence
      interval per standard deviation increase in D-dimer and vWF were 1.24 [95%
      confidence interval, 1.08-1.44] and 1.25 [95% confidence interval, 1.09-1.45],
      respectively). No associations were seen with tPA after adjustment. The positive
      associations between D-dimer and vWF and incident stroke remained after
      additional adjustment for markers of inflammation (C-reactive protein, IL-6). D
      dimer was associated with stroke in both normotensive and hypertensive men; vWF
      showed stronger associations in normotensive than in hypertensive men (test for
      interaction: P=0.52 for D-dimer; P<0.01 for vWF). CONCLUSIONS: Fibrin D-dimer and
      vWF are associated with increased risk of stroke in older men. These associations
      were not explained by their associations with inflammation. D-dimer may be a
      useful marker to identify those at high risk for stroke among hypertensive men.

PMID- 22382158
TI  - Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: Diabetes increases stroke risk, but whether diabetes
      status immediately before stroke improves prediction and whether duration is
      important are less clear. We hypothesized that diabetes duration independently
      predicts ischemic stroke. METHODS: Among 3298 stroke-free participants in the
      Northern Manhattan Study, baseline diabetes and age at diagnosis were determined.
      Incident diabetes was assessed annually (median, 9 years). Cox proportional
      hazard models were used to estimate hazard ratios (HR) and 95% CI for incident
      ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate,
      and duration of diabetes as a time-varying covariate; models were adjusted for
      demographic and cardiovascular risk factors. RESULTS: Mean age was 69 +/- 10
      years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and
      10% had development of diabetes. There were 244 ischemic strokes, and both
      baseline diabetes (HR, 2.5; 95% CI, 1.9-3.3) and diabetes considered as a time
      dependent covariate (HR, 2.4; 95% CI, 1.8-3.2) were similarly associated with
      stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted
      HR, 1.03 per year with diabetes; 95% CI, 1.02-1.04). Compared to nondiabetic
      participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1
      2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1-3.0), and >= 10 years
      (adjusted HR, 3.2; 95% CI, 2.4-4.5) were at increased risk. CONCLUSIONS: Duration
      of diabetes is independently associated with ischemic stroke risk adjusting for
      risk factors. The risk increases 3% each year, and triples with diabetes >= 10
      years.

PMID- 22382159
TI  - Prevalence and length of recovery of pusher syndrome based on cerebral
      hemispheric lesion side in patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine if side of
      cerebral hemisphere lesion affects the prevalence and time course of pushing
      behavior (PB) after stroke. METHODS: A total of 1660 patients with acute stroke
      were investigated. PB was assessed using the standardized Scale for Contraversive
      Pushing. Risk ratios were used to evaluate the differences in the prevalence of
      PB between right cerebral hemisphere-damaged (RCD) and left cerebral hemisphere
      damaged (LCD) patients. The differences in the time course among 35 (27 RCD and 8
      LCD) patients were evaluated by analyzing Scale for Contraversive Pushing scores
      with the Kaplan-Meier method using a log-rank test. RESULTS: PB was observed in
      156 (9.4%) patients. The prevalence of PB was significantly higher in RCD (97 of
      556 [17.4%]) than in LCD (57 of 599 [9.5%]) patients; risk ratio was 1.83 (95%
      CI, 1.35-2.49). The log-rank test indicated that RCD patients exhibited a
      significantly slower recovery than LCD patients (P=0.027). CONCLUSIONS: The
      number of RCD patients who exhibited PB was higher than that of LCD patients. The
      duration of recovery from PB was longer in RCD patients than in LCD patients.

PMID- 22382160
TI  - Neurointerventional procedural volume per hospital in United States: implications
      for comprehensive stroke center designation.
AB  - BACKGROUND AND PURPOSE: Availability of neurointerventional procedures is
      recommended as a necessary component of a comprehensive stroke center by various
      regulatory guidelines that also emphasize adequate procedural volumes. We studied
      the volumes of neurointerventional procedures performed in various hospitals
      across the United States with subsequent comparisons with rates of minimum
      procedural volumes recommended by various professional bodies or used in clinical
      trials to ensure adequate operator experience. METHODS: We reviewed the
      Nationwide Inpatient Sample database in the United States for the years 2005 to
      2008. Using International Classification of Disease-Clinical Modification, 9th
      revision, and Medicare severity diagnosis-related group codes, we identified
      among hospitals that admit stroke patients those that met the minimum criteria
      for overall and individual procedural volumes specified in various guidelines. We
      then compared the characteristics between the high-volume hospitals that
      performed at least 100 cervicocerebral angiograms and met >=1 other procedural
      criterion (n=79) and low-volume hospitals (n=958). RESULTS: Proportions of
      hospitals that met individual procedural volume criteria over the 4-year period
      according to procedure were: cervicocerebral angiography (7.0%-7.8%);
      endovascular acute ischemic stroke treatments (0.4%-2.6%); carotid
      angioplasty/stent placement (3.0%-5.3%); intracranial angioplasty/stent placement
      (0.3%-1.3%); and aneurysm embolization (1.3%-2.6%). There were significant trends
      for increasing numbers of all the endovascular procedures except intracranial
      angioplasty/stent placement over the course of 4 years. The high-volume hospitals
      were more likely to be urban teaching hospitals (70.9% versus 13.1%; P<0.001),
      had larger bed size (79.7% versus 26.9%; P<0.001), and had significantly higher
      rates of hemorrhagic stroke admissions and lower rates of transient ischemic
      attack admissions. Urban teaching location/status (OR, 8.92; CI, 4.3-18.2;
      P<0.001) and large bed size (OR, 4.40; CI, 2.0-9.5; P<0.001) remained as
      independent predictors of a high-volume hospital when adjusted for age, gender,
      risk factors, and stroke subtype. CONCLUSIONS: There are very few hospitals in
      the United States that meet all the neurointerventional procedural volume
      criteria for all endovascular procedures recommended to ensure adequate operator
      experience. Our results support the creation of specialized regional centers for
      ensuring adequate procedural volume within treating hospitals.

PMID- 22382161
TI  - Do different metabolic syndrome definitions predict cerebrovascular events and
      coronary heart disease independent of their components?: 9 years follow-up of the
      tehran lipid and glucose study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine whether
      metabolic syndrome (MetS), applying different definitions, predicts incident
      coronary heart disease (CHD) and cerebrovascular events (CVAs) independent of its
      components. METHODS: Among 2548, aged >= 50 years, World Health Organization,
      International Diabetes Federation, and Joint Interim Statement criteria were used
      to define MetS. Cox proportional hazards regression was implemented to estimate
      hazard ratios of incident CVA and CHD. RESULTS: During 9.3 years of follow-up, 72
      and 343 cases of CVA and CHD events occurred. The multivariate hazard ratios (95%
      CI) of incident CVA and CHD were 2.71 (1.57-4.68) and 2.07 (1.63-2.64) for MetS
      as defined by the Joint Interim Statement, respectively. There was no difference
      among the 3 definitions of MetS regarding the prediction of the CVA incidence.
      However, MetS as defined by the Joint Interim Statement predicted CHD better than
      the International Diabetes Federation definition. After adjustment for
      components, MetS lost its association with CHD and CVA; in this model, the
      elevated blood pressure and high fasting plasma glucose (International Diabetes
      Federation definition) showed significant risk for CVA events; regarding CHD
      events, the elevated blood pressure, high fasting plasma glucose, and, for World
      Health Organization definition, obesity and dyslipidemia remained as predictors.
      CONCLUSIONS: All definitions of MetS were associated with CVA and CHD events.
      After adjusting its components, MetS lost its association with incident CVA and
      CHD; however, elevated blood pressure for both CVA and CHD events and high
      fasting plasma glucose for CHD events remained as independent predictors in all
      definitions.

PMID- 22382162
TI  - Patient-reported auditory functions after stroke of the central auditory pathway.
AB  - BACKGROUND AND PURPOSE: Auditory functional limitations experienced by patients
      after stroke of the central auditory pathways remain underinvestigated. Purpose-
      To measure patient-reported hearing difficulties in everyday life in nonaphasic
      patients with stroke of the auditory brain versus normal control subjects. To
      examine how hearing difficulties correlate with auditory tests and site of lesion
      in individual cases. METHODS: We recruited 21 individuals with auditory brain
      stroke (excluding those with aphasia) diagnosed on the basis of a brain MRI
      conducted 1 to 2 weeks after the stroke and assessed in the chronic stage of
      stroke. Twenty-three controls matched for age and hearing were also recruited.
      All subjects completed the Amsterdam Inventory for Auditory Disability
      (consisting of subscales of sound detection, recognition, localization, speech in
      quiet, speech in noise) and underwent baseline audiometry and central auditory
      processing tests (dichotic digits, frequency and duration patterns, gaps in
      noise). RESULTS: Sound recognition and localization subscores of the inventory
      were significantly worse in case subjects versus control subjects, with severe
      and significant functional limitation (z score >3) reported by 9 out of 21 case
      subjects. None of the inventory subscales correlated with audiometric thresholds,
      but localization and recognition subscales showed a moderate to strong
      correlation with dichotic digits (left ear) and pattern tests. CONCLUSIONS: A
      substantial proportion of patients may experience and report severe auditory
      functional limitations not limited to speech sounds after stroke of the auditory
      brain. A hearing questionnaire may help identify patients who require more
      extensive assessment to inform rehabilitation plans.

PMID- 22382164
TI  - A biomimetic approach towards synthesis of zinc oxide nanoparticles.
AB  - Using natural processes as inspiration, the present study demonstrates a positive
      correlation between zinc metal tolerance ability of a soil fungus and its
      potential for the synthesis of zinc oxide (ZnO) nanoparticles. A total of 19
      fungal cultures were isolated from the rhizospheric soils of plants naturally
      growing at a zinc mine area in India and identified on the genus, respectively
      the species level. Aspergillus aeneus isolate NJP12 has been shown to have a high
      zinc metal tolerance ability and a potential for extracellular synthesis of ZnO
      nanoparticles under ambient conditions. UV-visible spectroscopy, Fourier
      transform infrared spectroscopy, X-ray diffraction analysis, transmission
      electron microscopy, and energy dispersive spectroscopy studies further confirmed
      the crystallinity, morphology, and composition of synthesized ZnO nanoparticles.
      The results revealed the synthesis of spherical nanoparticles coated with protein
      molecules which served as stabilizing agents. Investigations on the role of
      fungal extracellular proteins in the synthesis of nanoparticles indicated that
      the process is nonenzymatic but involves amino acids present in the protein
      chains.

PMID- 22382163
TI  - Covert neurological symptoms associated with silent infarcts from midlife to
      older age: the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND AND PURPOSE: Unrecognized or unreported stroke-like symptoms, called
      covert symptoms, occur in persons free of clinical stroke. Whether covert
      symptoms are associated with subclinical brain infarcts (SBIs) is unknown. This
      study examined the association between covert stroke-like symptoms and SBI/stroke
      in persons with no history of stroke or transient ischemic attack. METHODS: A
      total of 1881 Atherosclerosis Risk in Communities (ARIC) participants free of
      clinical stroke or transient ischemic attack (40% male, 50% black, 47-70 years)
      were queried for covert symptoms and underwent cerebral MRI during the baseline
      MRI visit. Symptoms were reassessed after 3 years at Visit 4 (n=1001; 39% male,
      50% black) and approximately 10 years with a follow-up MRI (n=1006; 40% male, 50%
      black, 61-83 years). RESULTS: Covert symptoms were associated with prevalent SBI
      (OR, 1.94; 95% CI, 1.21-3.11; P=0.006). No support was found for associations
      between baseline MRI symptoms and SBI at the follow up MRI visit. In participants
      without SBI at baseline, symptoms at Visit 4 (OR, 2.96; 1.23-7.13; P=0.016) and
      symptoms at the follow-up MRI visit (OR, 4.29; 2.51-7.33; P<0.001) were
      associated with a combined outcome of new SBI/clinical stroke on follow-up MRI.
      Covert symptoms at follow-up MRI visit were also associated with having new SBI
      (OR, 2.26; 1.18-4.32; P=0.014) on the follow-up MRI that were not seen on the
      baseline MRI. CONCLUSIONS: Covert neurological symptoms were associated with
      prevalent SBI, and when ascertained at the time of follow-up MRI, with new SBI.
      Covert symptoms may reflect heightened risk for infarcts.

PMID- 22382165
TI  - The effects of pH oscillation on Lactobacillus rhamnosus batch cultivation.
AB  - Inhomogeneous mixing in industrial-sized fermentation processes causes
      oscillations in process parameters such as temperature or pH value in the
      cultivation medium, which causes stress to the bacteria being cultivated. In this
      work, the impact of extracellular pH oscillations on the production of
      Lactobacillus rhamnosus, a well-studied probiotic bacteria, were investigated by
      means of a scale-down batch process, simulating inhomogeneous pH values by
      controlling the pH value of the medium on sinusoidal trajectories. Effects of pH
      stimulation on the bacteria were assessed by testing storage and freeze-drying
      stability of harvested cells, two factors relevant for the industrial process.
      Furthermore, gene expressions of six selected genes, i.e. atpA, fat, cfa, groEL,
      hrcA, and pstS, known to be related to stress response were monitored. Although
      storage stability is only slightly negatively affected by pH stimulation of the
      bacteria, gene expression of four of the studied genes, i.e. fat, hrcA, groEL,
      and pstS show to correlate with amplitude and frequency of the oscillation.

PMID- 22382166
TI  - Structural analysis and biosynthetic engineering of a solubility-improved and
      less-hemolytic nystatin-like polyene in Pseudonocardia autotrophica.
AB  - Polyene antibiotics such as nystatin are a large family of very valuable
      antifungal polyketide compounds typically produced by soil actinomycetes.
      Previously, using a polyene cytochrome P450 hydroxylase-specific genome screening
      strategy, Pseudonocardia autotrophica KCTC9441 was determined to contain an
      approximately 125.7-kb region of contiguous DNA with a total of 23 open reading
      frames, which are involved in the biosynthesis and regulation of a structurally
      unique polyene natural product named NPP. Here, we report the complete structure
      of NPP, which contains an aglycone identical to nystatin and harbors a unique di
      sugar moiety, mycosaminyl-(alpha1-4)-N-acetyl-glucosamine. A mutant generated by
      inactivation of a sole glycosyltransferase gene (nppDI) within the npp gene
      cluster can be complemented in trans either by nppDI-encoded protein or by its
      nystatin counterpart, NysDI, suggesting that the two sugars might be attached by
      two different glycosyltransferases. Compared with nystatin (which bears a single
      sugar moiety), the di-sugar containing NPP exhibits approximately 300-fold higher
      water solubility and 10-fold reduced hemolytic activity, while retaining about
      50% antifungal activity against Candida albicans. These characteristics reveal
      NPP as a promising candidate for further development into a pharmacokinetically
      improved, less-cytotoxic polyene antifungal antibiotic.

PMID- 22382167
TI  - Red mold, diabetes, and oxidative stress: a review.
AB  - Type 2 diabetes is a major health concern and a rapidly growing disease with a
      modern etiology, which produces significant morbidity and mortality. The optimal
      management of type 2 diabetes aims to control hyperglycemia, hypertension, and
      dyslipidemia to reduce overall risks. Diabetes and its complications usually
      develop as oxidative stress increases. Monascus-fermented rice, also called red
      mold rice or red mold dioscorea are used in China to enhance food color and
      flavor. Red mold-fermented products are popular health foods that are considered
      to have antiobesity, antifatigue, antioxidation, and cancer prevention effects.
      This review article describes the antidiabetic and antioxidative stress effects
      on humans and animals of red mold-fermented products or their secondary
      metabolites.

PMID- 22382168
TI  - Dengue virus-like particles: construction and application.
AB  - Virus-like particles (VLPs) are shell-like viruses that lack virus-specific
      genetic materials. Many viral-structured proteins can assemble into VLPs, which
      mimic the overall structure of virus particles and can elicit strong immune
      responses in a host. Dengue viruses (DENVs), from the genus Flavivirus, are
      transmitted to humans through the bites of an infected Aedes mosquito. DENVs
      cause several diseases that prevailed mainly in tropical and subtropical areas.
      However, effective treatment measures and preventive strategies for dengue
      diseases are still lacking. The present minireview summarized the assembly and
      maturation of DENVs, the strategies and effective factors for dengue VLP
      construction, and the application of DENV VLPs.

PMID- 22382169
TI  - Combinatorial approach of statistical optimization and mutagenesis for improved
      production of acidic phytase by Aspergillus niger NCIM 563 under submerged
      fermentation condition.
AB  - Combination of statistical optimization and mutagenesis to isolate hypersecretory
      strains is studied to maximize phytase production from Aspergillus niger NCIM 563
      under submerged fermentation. The overall results obtained show a remarkable 5.98
      fold improvement in phytase production rates when compared to that using basal
      medium. Optimization of culture conditions from parent strain is studied first by
      the Plackett-Burman technique to evaluate the effects of 11 variables for phytase
      production. The results showed that glucose, MgSO(4), KCl, incubation period, and
      MnSO(4) are the most significant variables affecting enzyme production. Further
      optimization in these variables, using a central composite design technique,
      resulted in 3.74-fold increase in the yield of phytase production to 254,500 U/l
      when compared with the activity observed with basal media (68,000 U/l) in shake
      flask. Our experiments show that the phytase from A. niger NCIM 563 exhibits
      desirable activity in simulated gastric fluid conditions with low pH and also
      improved thermostability when compared to commercial phytase. The improved yield
      demonstrates the potential applicability of phytase enzyme as a source of phytase
      supplement for phosphorus nutrition and environmental protection in animal feed
      industry. Physical and chemical mutagenesis experiments were carried out in
      parallel to isolate hypersecretory mutants that could possibly further enhance
      the enzyme production. Using optimized media conditions of the parent strain, our
      results show that mutant strain A. niger NCIM 1359 increased the phytase activity
      by another 1.6-fold to 407,200 U/l.

PMID- 22382170
TI  - Recumbent stepper submaximal exercise test to predict peak oxygen uptake.
AB  - PURPOSE: The purpose of this study was to examine the ability of the YMCA
      submaximal exercise test protocol using a total body recumbent stepper to predict
      VO(2peak). METHODS: Of 112 individuals initially screened, 110 individuals with
      low to moderate cardiovascular disease risk met the inclusion criteria for
      participation in the study. The maximal exercise test used a motorized treadmill
      and the Bruce or modified Bruce protocol. Oxygen uptake was measured and analyzed
      through collection of expired gases using a metabolic measurement system. The
      submaximal exercise test was performed at least 24 h later but no more than 5 d
      after maximal exercise testing. Participants were instructed to keep a pace of
      100 steps per minute and the resistance increase every 3 min according to the
      protocol until fatigue, or until 85% of HR max was achieved. A cross-validation
      study was also performed to determine the accuracy of the prediction equation.
      RESULTS: Using a stepwise regression, we report that VO(2peak) can be predicted
      using a five-element model including age, weight, sex, wattsend_submax, and
      HRend_submax (F5,69 = 70.31, P < 0.001). We report a strong correlation between
      the predicted VO(2peak) to the actual VO(2peak). CONCLUSIONS: These data suggest
      the YMCA submaximal exercise test can be used with the total body recumbent
      stepper to predict VO(2peak) in healthy adults.

PMID- 22382171
TI  - Modeling the expenditure and reconstitution of work capacity above critical
      power.
AB  - PURPOSE: The critical power (CP) model includes two constants: the CP and the W'
      [P = (W' / t) + CP]. The W' is the finite work capacity available above CP. Power
      output above CP results in depletion of the W' complete depletion of the W'
      results in exhaustion. Monitoring the W' may be valuable to athletes during
      training and competition. Our purpose was to develop a function describing the
      dynamic state of the W' during intermittent exercise. METHODS: After
      determination of VO(2max), CP, and W', seven subjects completed four separate
      exercise tests on a cycle ergometer on different days. Each protocol comprised a
      set of intervals: 60 s at a severe power output, followed by 30-s recovery at a
      lower prescribed power output. The intervals were repeated until exhaustion.
      These data were entered into a continuous equation predicting balance of W'
      remaining, assuming exponential reconstitution of the W'. The time constant was
      varied by an iterative process until the remaining modeled W' = 0 at the point of
      exhaustion. RESULTS: The time constants of W' recharge were negatively correlated
      with the difference between sub-CP recovery power and CP. The relationship was
      best fit by an exponential (r = 0.77). The model-predicted W' balance correlated
      with the temporal course of the rise in VO(2) (r = 0.82-0.96). The model
      accurately predicted exhaustion of the W' in a competitive cyclist during a road
      race. CONCLUSIONS: We have developed a function to track the dynamic state of the
      W' during intermittent exercise. This may have important implications for the
      planning and real-time monitoring of athletic performance.

PMID- 22382172
TI  - Iron status is associated with endurance performance and training in female
      rowers.
AB  - PURPOSE: Studies in animals and humans show a link between iron depletion without
      anemia (IDNA) and physical performance. Consequences of IDNA relevant to athletes
      include reduced endurance and energetic efficiency. We conducted this cross
      sectional study to investigate the relationships between iron status,
      performance, and training in nonanemic female rowers. METHODS: Iron status
      (hemoglobin, serum ferritin, soluble transferrin receptor) of 165 rowers was
      assessed at the beginning of a training season; 27% (n = 44) of rowers were
      identified as IDNA (serum ferritin < 20.0 MUg.L) and 10% as anemic (n = 16,
      hemoglobin < 12.0 g.dL). Physical performance of 48 nonanemic rowers (n = 24
      normal, n = 24 depleted) was assessed (VO(2peak), 4-km time, gross energetic
      efficiency), and training was recorded. Daily training load was calculated using
      the session RPE method (training duration * intensity rating). RESULTS: There
      were no significant differences between the two groups of iron status in any of
      the potential confounders of the association between iron status and performance
      that were tested. Compared with rowers with normal iron status, rowers with
      depleted iron trained ~10 min less per day (P = 0.02) and had a 0.3-L.min lower
      VO(2peak) (P = 0.03). Both serum ferritin and training group (high vs low based
      on a session RPE of 3200) were positively related to VO(2peak). Less highly
      trained rowers with poor iron status had a lower VO(2peak) (-0.32 L.min, P =
      0.02) and were less energetically efficient (-1.7%, P = 0.09) compared with more
      highly trained rowers with poor iron status. CONCLUSIONS: Impaired iron status is
      a prevalent problem among female endurance athletes. The relationship between
      rowers' iron status and endurance performance varied depending on training load.
      IDNA may prevent rowers from training as hard, directly affecting their
      performance.

PMID- 22382173
TI  - Moving on with challenges & new initiatives.

PMID- 22382174
TI  - Elimination of leprosy & possibility of eradication - the Indian scenario.

PMID- 22382175
TI  - Rapid molecular diagnosis of spinal muscular atrophy.

PMID- 22382176
TI  - Thyroid bone disease.

PMID- 22382177
TI  - Cytogenetic study in CML.

PMID- 22382179
TI  - Expression of telomerase & its significance in the diagnosis of pancreatic
      cancer.
AB  - Pancreatic cancer has one of the worst prognoses among all types of cancers. The
      survival rate is less than 5 per cent; this is due to difficulty in diagnosing at
      an early stage. Despite the improvements in diagnostic imaging techniques such as
      computed tomography, magnetic resonance imaging, etc., the early diagnosis of
      pancreatic cancer is still difficult. Alternative methods of diagnosing
      pancreatic cancer at an early stage are presently been explored. The detection of
      telomerase activity has been proposed to be a useful tool in the diagnosis of
      pancreatic cancer. Telomerase is made up of three major parts namely, human
      telomerase reverse transcriptase, human telomerase and telomerase -associated
      protein. Several researchers have shown telomerase activity in tissues and fluids
      of patients with pancreatic and other types of cancers. About 95 per cent
      telomerase activity has been detected in pancreatic adenocarcinoma. Since
      telomerase activity is present in a vast majority of human cancers, it might have
      a role in the diagnosis and treatment of cancer.

PMID- 22382178
TI  - Stem cell therapy: a novel & futuristic treatment modality for disaster injuries.
AB  - Stem cell therapy hold the potential to meet the demand for transplant
      cells/tissues needed for treating damages resulting from both natural and man
      made disasters. Pluripotency makes embryonic stem cells and induced pluripotent
      stem cells ideal for use, but their teratogenic character is a major hindrance.
      Therapeutic benefits of bone marrow transplantation are well known but
      characterizing the potentialities of haematopoietic and mesenchymal cells is
      essential. Haematopoietic stem cells (HSCs) have been used for treating both
      haematopoietic and non-haematopoietic disorders. Ease of isolation, in vitro
      expansion, and hypoimmunogenecity have brought mesenchymal stem cells (MSCs) into
      limelight. Though differentiation of MSCs into tissue-specific cells has been
      reported, differentiation-independent mechanisms seem to play a more significant
      role in tissue repair which need to be addressed further. The safety and
      feasibility of MSCs have been demonstrated in clinical trials, and their use in
      combination with HSC for radiation injury treatment seems to have extended
      benefit. Therefore, using stem cells for treatment of disaster injuries along
      with the conventional medical practice would likely accelerate the repair process
      and improve the quality of life of the victim.

PMID- 22382180
TI  - Allele-specific PCR for a cost-effective & time-efficient diagnostic screening of
      spinal muscular atrophy.
AB  - BACKGROUND & OBJECTIVES: Genetic diagnosis of spinal muscular atrophy (SMA) is
      complicated by the presence of SMN2 gene as majority of SMA patients show absence
      or deletion of SMN1 gene. PCR may amplify both the genes non selectively in
      presence of high amount of DNA. We evaluated whether allele-specific PCR for
      diagnostic screening of SMA is reliable in the presence of high amount of genomic
      DNA, which is commonly used when performing diagnostic screening using
      restriction enzymes. METHODS: A total of 126 blood DNA samples were tested in
      amounts ranging 80-200 ng, referred for the genetic diagnosis of SMA using both
      conventional PCR-RFLP and allele-specific PCR. RESULTS: The results from both
      methods showed agreement. Further, allele-specific PCR was found to be a time
      efficient and cost-effective method. INTERPRETATION & CONCLUSIONS: Our study
      demonstrated the accuracy of our allele-specific PCR and the results were
      comparable compatible with that of PCR-RFLP, indicating its practical application
      in SMA diagnostic screening.

PMID- 22382181
TI  - Bone mineral density in patients of Graves disease pre- & post-treatment in a
      predominantly vitamin D deficient population.
AB  - BACKGROUND & OBJECTIVES: Hyperthyroidism causes bone loss, and its treatment may
      restore bone mass, however, concomitant vitamin D deficiency may prevent this. We
      undertook this study to measure the bone mineral density (BMD) 25 (OH) vitamin D
      levels in patients with Graves disease in our population which is predominently
      vitamin D deficient and how we change with when patients become euthyroid.
      METHODS: The biochemical, thyroid functions, serum vitamin D levels and BMD were
      estimated in 80 consecutive patients with Graves and 80 euthyroid controls.
      Patients were treated and rendered euthyroid. Fifty four completed one year, and
      27 completed two years of follow up. RESULTS: Patients had significant reduced
      BMD during hyperthyroid state compared to normal healthy controls. The mean
      vitamin D levels at baseline were in the insufficient range both patients (12.67
      +/- 6.24 ng/ml) and controls (10.99 +/- 7.05 ng/ml). The BMD improved at all
      sites with antithyroid treatment. But, the BMD adjusted for body mass index (BMI)
      and age at all sites showed significant decrease with time. INTERPRETATION &
      CONCLUSIONS: Age and body mass index positively correlated with BMD. There was
      improvement in absolute BMD of patients at one and two years of follow up. When
      the BMD was adjusted for age and BMI, there was a decrease in BMD at one year
      which was less in the second year including that the damage in BMD caused by
      thyroid hormone excess is not made up even after two years of patient being
      euthyroid. Whether vitamin D replacement would change this needs to be studied.

PMID- 22382182
TI  - Cytogenetic & molecular analyses in adult chronic myelogenous leukaemia patients
      in north India.
AB  - BACKGROUND & OBJECTIVES: Chronic myelogenous leukaemia (CML) is the commonest
      leukaemia in Asia. There is a paucity data on cytogenetic and molecular analyses
      of Indian CML patients. This apparently reflects the low availability of
      cytogenetic and molecular techniques in our country. This study aimed to document
      various types of BCR-ABL fusion transcripts in different phases of CML and to
      compare the Ph chromosome positivity/negativity vis-a-vis BCR-ABL fusion
      transcripts in adult CML patients. METHODS: Between June 2004 and February 2009,
      208 patients were diagnosed as CML in chronic phase (CP), accelerated phase (AP)
      and blast crisis (BC), according to standard criteria. Cytogenetic and molecular
      genetic analyses were performed in all patients. Various types of BCR-ABL hybrid
      transcripts were compared with phases of CML and cytogenetic abnormalities.
      RESULTS: Among 208 CML patients, b3a2 BCR-ABL transcripts were most commonly
      detected (66.82%) followed by b2a2 (28.84%), b3a2 + b2a2 (3.36%), b3a2 + e19a2
      (0.48%) and b2a2 + e19a2 (0.48%). b3a2 transcripts were more frequently detected
      than b2a2 transcripts, in the whole group of 208 as well as in 183 CML-CP
      patients (P<0.0001). Ph chromosome was positive in 135 of 139 patients with b3a2
      transcripts and 56 of 60 patients with b2a2 transcripts, difference not being
      significant. Additional cytogenetic abnormalities detected in 3.8 per cent
      patients in CML-CP and 44 per cent patients in CML-AP/BC, did not show
      predilection for any BCR-ABL transcript type. INTERPRETATION & CONCLUSIONS: This
      study documents higher Ph positivity (96.15%) by cytogenetic analysis among CML
      patients, as confirmed by qualitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis in a large patient group from north India. Both the
      techniques contribute towards understanding the disease biology, and have
      important implications for diagnosis and management of CML patients.

PMID- 22382183
TI  - Assessment of effects on health due to consumption of bitter bottle gourd
      (Lagenaria siceraria) juice.
AB  - BACKGROUND & OBJECTIVES: The bottle gourd (Lagenaria siceraria) is popularly
      known as lauki, ghia or dudhi in India. Its consumption is advocated by
      traditional healers for controlling diabetes mellitus, hypertension, liver
      diseases, weight loss and other associated benefits. However, in last few years
      there have been reports of suspected toxicity due to consumption of its juice.
      This led to the constitution of an Expert Committee by Department of Health
      Research at Indian Council of Medical Research (ICMR), Ministry of Health &
      Family Welfare, Government of India in October 2010. The committee looked into
      the issues related to safety of consumption of bottle gourd juice, and this paper
      presents the findings. METHODS: Information on cases of suspected toxicity due to
      consumption of bottle gourd juice was collected by internet search, advertising
      on website of ICMR and by writing to State and district health authorities as
      well as to medical colleges, hospitals and private nursing homes across the
      country. RESULTS: Three deaths were reported, one from Delhi and two from Uttar
      Pradesh after consumption of extremely bitter bottle gourd juice. Three persons
      who died after consumption of freshly prepared bottle gourd juice or juice mixed
      with bitter gourd (karela) juice were over 59 years of age and had diabetes since
      last 20 years. This juice was reported to be extremely bitter by all three.
      Twenty six persons were admitted to various hospitals of the country on complaint
      of abdominal pain and vomiting following consumption of freshly prepared bottle
      gourd juice. Diarrhoea and vomiting of blood (haematemesis) was reported in 18
      (69.2%) and 19 (73.1%) patients, respectively. Biochemical investigations
      revealed elevated levels of liver enzymes. More than 50 per cent patients had
      hypotension. Endoscopic findings showed profusely bleeding stomach with excessive
      ulceration seen in distal oesophagus, stomach and duodenum in most of the cases.
      All these patients recovered fully and no sequeale was recorded for any of the
      cases. INTERPRETATION & CONCLUSIONS: Cucurbitaceae family, of which bottle gourd
      is a member contains the toxic tetracyclic triterpenoid compounds called
      cucurbitacins which are responsible for the bitter taste. There is no known
      antidote for this toxicity and clinicians treat such cases symptomatically only.
      The Committee made the following recommendations: (i) The community needs to be
      educated that bitter tasting bottle gourd juice should not be consumed and in
      case there is any discomfort, nausea, vomiting, diarrhoea or any feeling of
      uneasiness after consumption of juice, the person should immediately be taken to
      a nearby hospital. (ii) Clinicians are suggested that patients coming with
      symptoms (discomfort, nausea, vomiting, diarrhoea, gastrointestinal bleeding
      after consumption of juice) should immediately be attended to and general
      supportive care should be provided, i.e. IV fluids/crystalloids/blood
      products/fresh frozen plasma to maintain the haemodynamics and electrolyte
      balance; Ryle's tube to be put in for gastric lavage and to assess
      gastrointestinal (GI) bleed- aspirate to be preserved; Proton pump inhibitors
      should be given for management of GI bleed and appropriate treatment for other
      complications should be given. (iii) The possible research areas identified are
      chemical composition studies on bitter and normal bottle gourd and other members
      of cucurbitaceae family; animal toxicity studies and studies on interaction
      between bottle gourd juice and other drugs.

PMID- 22382184
TI  - Is RSBY India's platform to implementing universal hospital insurance?
AB  - BACKGROUND & OBJECTIVES: In 2008, India's Labour Ministry launched a hospital
      insurance scheme called Rashtriya Swasthya Bima Yojana (RSBY) covering 'Below
      Poverty Line' (BPL) households. RSBY is implemented through insurance companies;
      premiums are subsidized by Union and States governments (75 : 25%). We examined
      RSBY's enrolment of BPL, costs vs. budgets and policy ramifications. METHODS:
      Numbers of BPL are obtained by following criteria of two committees appointed for
      this task. District-specific premiums are weighted to obtain national average
      premiums. Using the BPL estimates and national premiums, we calculated overall
      expected costs of full roll-out of the RSBY per annum, and compared it to Union
      government budget allocations. RESULTS: By March 31, 2011, RSBY enrolled about
      27.8 per cent of the number of BPL households following the Tendulkar Committee
      estimates (37.6% following the Lakdawala Committee criteria). The average
      national weighted premium was Rs. 530 per household per year in 2011. The
      expected cost of premium to the union government of enrolling the entire BPL
      population in financial year (FY) 2010-11 would be Rs. 33.5 billion using
      Tendulkar count of BPL (or Rs. 24.6 billion following Lakdawala count),
      representing about 0.3 per cent (or 0.2%, respectively) of the total union
      budget. The RSBY budget allocation for FY 2010-11 was only about 0.037 per cent
      of the total union budget, sufficient to pay premiums of only 34 per cent of the
      BPL households enrolled by March 31, 2011. INTERPRETATION & CONCLUSIONS: RSBY
      could be the platform for universal health insurance when (i) the budget
      allocation will match the required funds for maintenance and expansion of the
      scheme; (ii) the scheme would ensure that beneficiaries' rights are legally
      anchored; and (iii) RSBY would attract large numbers of premium-paying (non-BPL)
      households.

PMID- 22382186
TI  - The normal range of body mass index with high body fat percentage among male
      residents of Lucknow city in north India.
AB  - BACKGROUND & OBJECTIVES: Several studies have raised the suspicion that the body
      mass index (BMI) cut-off for overweight as defined by the WHO may not adequately
      reflect the actual overweight status. The present study looked at the
      relationship between BMI and body fat per cent (BF %) / health risks
      (hypertension and type 2 diabetes) in male residents of Lucknow city, north India
      to evaluate the validity of BMI cut-off points for overweight. METHODS: One
      thousand one hundred and eleven male volunteer subjects (18-69 yr) who
      participated in different programmes organized by the Institute during 2005 to
      2008 were included in the study. BF% was measured using commercially available
      digital weight scale incorporating bioelectrical impedance (BI) analyzer. The
      proposed cut-off for BMI based on BF % was calculated using receiver operating
      characteristics (ROC) curve analysis. RESULTS: Forty four per cent subjects
      showed higher BF % (>25%) with BMI range (24-24.99 kg/m2). Sensitivity and
      specificity at BMI cut-off at 24.5 kg/m3 were 83.2 and 77.5, respectively.
      Sensitivity at BMI cut-off >25 kg/m2 was reduced by 5 per cent and specificity
      increased by 4.6 per cent when compared to 24.5 cut-off. INTERPRETATION &
      CONCLUSIONS: The study subjects showed higher body fat percentage and risk
      factors like hypertension and type 2 diabetes at normal BMI range proposed by the
      WHO. The cut-off for BMI was proposed to be 24.5 kg/m2 for our study population.
      If overweight is regarded as an excess of body fat and not as an excess of weight
      (increased BMI), the cut-off points for overweight based on BMI would need to be
      lowered. However, the confidence of estimate of the BMI cut-off in the present
      study may be considered with the limitations of BI analysis studies.

PMID- 22382185
TI  - Polymorphisms in base-excision & nucleotide-excision repair genes & prostate
      cancer risk in north Indian population.
AB  - BACKGROUND & OBJECTIVES: Genetic variation in the DNA repair genes might be
      associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited
      polymorphisms may increase the susceptibility to cancers. Base excision and
      nucleotide excision are the two major repair pathways. We investigated the
      association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon
      7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with
      risk of prostate cancer (PCa). METHODS: The study was designed with 192
      histopathologically confirmed PCa patients and 224 age matched healthy controls
      of similar ethnicity. Genotypes were determined by amplification refractory
      mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP)
      methods. RESULTS: Overall, a significant association in NER gene, XPC PAT Ins/Ins
      (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33,
      P=0.012). XPC exon 15 variant CC genotypes presented statistically significant
      risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no
      association was observed for polymorphism with BER genes. Diplotype analysis of
      XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was
      statistically significant in PCa. The variant genotypes of NER genes were also
      associated with high Gleason grade. INTERPRETATION & CONCLUSIONS: The results
      indicated that there was a significant modifying effect on the association
      between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further
      confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian
      population.

PMID- 22382187
TI  - Comparison of thrice daily biphasic human insulin (30/70) versus basal detemir &
      bolus aspart in patients with poorly controlled type 2 diabetes mellitus - a
      pilot study.
AB  - BACKGROUND & OBJECTIVES: Conventionally, biphasic human insulin (30/70, BHI) is
      used twice daily for the management of patients with diabetes. However, this
      regimen is suboptimal to control post-lunch and/or pre-dinner hyperglycaemia in
      some patients. This study was undertaken to compare the efficacy and safety of
      thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus
      aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM).
      METHODS: In this open labelled randomized pilot study, 50 patients with
      uncontrolled T2DM on twice-daily BHI and insulin sensitizers were randomized
      either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose
      profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost
      were compared between the two treatment groups at the end of 12 wk. RESULTS: Mean
      HbA l c (+/- SD) decreased from 9.0 +/- 0.9 per cent at randomization to 7.9 +/-
      0.8 per cent in BHI (P<0.001) and from 9.4 +/- 1.3 to 8.2 +/- 1.0 per cent in BB
      regimen (P<0.001) after 12 wk of treatment. The mean (+/- SEM) weight gain in
      patients in the BHI regimen was 1.5 +/- 0.33 kg compared to 1.4 +/- 0.34 kg in
      the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB
      regimen 0.46 +/- 0.32 U/kg/day compared to 0.15 +/- 0.21 U/kg/day in the BHI
      regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes
      was not different in both the regimen. The BB regimen was more expensive than the
      BHI regimen (P<0.001). INTERPRETATION & CONCLUSIONS: The thrice daily biphasic
      human insulin regimen is non-inferior to the basal bolus insulin analogue regimen
      in terms efficacy and safety in patients with poorly controlled T2DM. However,
      these data require further substantiation in large long term prospective studies.

PMID- 22382188
TI  - A pilot study on area under curve of mycophenolic acid as a guide for its optimal
      use in renal transplant recipients.
AB  - BACKGROUND & OBJECTIVES: The immunosuppressants administered to renal transplant
      subjects are usually monitored therapeutically to prevent graft rejection and
      drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present
      prospective study was undertaken to establish the utility of plasma level
      monitoring of MPA and to correlate it with clinical outcomes in renal transplant
      receipients. METHODS: MPA plasma level at 2, 4 and 9 h and the area under
      concentration-time curve (AUC) were estimated using high performance liquid
      chromatography in 24 renal transplant recipients receiving immunosuppressant MPA
      plus tacrolimus and steroid. RESULTS: There was wide inter-individual variation
      in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug
      events (diarrhoea and acidity) were significantly more in the high MPA AUC
      patients. Though biopsy proven acute rejection was not found, of the six subjects
      with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop
      tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and
      Gastrointestinal Quality of Life Index (GIQLI) scores represented better health
      related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l).
      INTERPRETATION & CONCLUSIONS: The present findings suggest the MPA AUC of 30 - 60
      mg.h/l in the maintenance stage of renal transplant patients to have optimum
      clinical benefit and relegated adverse events profile indicating the usefulness
      of AUC of MPA with limited sampling strategy in optimizing its use.

PMID- 22382189
TI  - Chromosomal abnormalities & oxidative stress in women with premature ovarian
      failure (POF).
AB  - BACKGROUND & OBJECTIVES: Premature ovarian failure (POF) is defined as the
      cessation of ovarian function under the age of 40 yr and is characterized by
      amenorrhoea, hypoestrogenism and elevated serum gonadotrophin levels. The cause
      of POF remains undetermined in majority of the cases. This study was aimed to
      investigate the type and frequency of cytogenetic abnormalities in patients with
      idiopathic POF and also to study the role of oxidative stress in such cases.
      METHODS: Seventy five women with idiopathic POF were included in this study.
      Chromosome analysis was done in peripheral blood lymphocytes by conventional GTG
      banding to identify numerical or structural abnormalities. Cytogenetically normal
      cases were investigated for reactive oxygen species (ROS) levels in their blood
      by luminol-chemiluminescence assay. RESULTS: Eighteen chromosomal anomalies were
      identified in POF patients (24%). Majority of the cases were found to have X
      chromosome abnormalities (28%). Overall median ROS range was found to be
      significantly higher (P<0.01) in POF patients [50480 (120,132966) RLU/min]
      compared to controls [340 (120,5094) RLU/min]. Among these, 50 per cent of the
      POF patients had higher ROS levels, 20 per cent had medium elevation and 30 per
      cent were found to have normal values comparable to controls. INTERPRETATION &
      CONCLUSIONS: X-chromosome anomalies were found to be the major contributor of
      POF. Oxidative stress may be the underlying aetiology in idiopathic premature
      ovarian failure. Thus the results of this study highlight the role of cytogenetic
      abnormalities and supraphysiological levels of ROS in causation of idiopathic
      POF. But the role of oxidative stress needs to be confirmed by other studies on
      patients from different geographical areas and from different ethnicities.

PMID- 22382190
TI  - Sex worker-led structural interventions in India: a case study on addressing
      violence in HIV prevention through the Ashodaya Samithi collective in Mysore.
AB  - BACKGROUND & OBJECTIVES: Structural interventions have the capacity to improve
      the outcomes of HIV/AIDS interventions by changing the social, economic,
      political or environmental factors that determine risk and vulnerability.
      Marginalized groups face disproportionate barriers to health, and sex workers are
      among those at highest risk of HIV in India. Evidence in India and globally has
      shown that sex workers face violence in many forms ranging from verbal,
      psychological and emotional abuse to economic extortion, physical and sexual
      violence and this is directly linked to lower levels of condom use and higher
      levels of sexually transmitted infections (STIs), the most critical determinants
      of HIV risk. We present here a case study of an intervention that mobilized sex
      workers to lead an HIV prevention response that addresses violence in their daily
      lives. METHODS: This study draws on ethnographic research and project monitoring
      data from a community-led structural intervention in Mysore, India, implemented
      by Ashodaya Samithi. Qualitative and quantitative data were used to characterize
      baseline conditions, community responses and subsequent outcomes related to
      violence. RESULTS: In 2004, the incidence of reported violence by sex workers was
      extremely high (> 8 incidents per sex worker, per year) but decreased by 84 per
      cent over 5 years. Violence by police and anti-social elements, initially most
      common, decreased substantially after a safe space was established for sex
      workers to meet and crisis management and advocacy were initiated with different
      stakeholders. Violence by clients, decreased after working with lodge owners to
      improve safety. However, initial increases in intimate partner violence were
      reported, and may be explained by two factors: (i) increased willingness to
      report such incidents; and (ii) increased violence as a reaction to sex workers'
      growing empowerment. Trafficking was addressed through the establishment of a
      self-regulatory board (SRB). The community's progressive response to violence was
      enabled by advancing community mobilization, ensuring community ownership of the
      intervention, and shifting structural vulnerabilities, whereby sex workers
      increasingly engaged key actors in support of a more enabling environment.
      INTERPRETATION & CONCLUSIONS: Ashodaya's community-led response to violence at
      multiple levels proved highly synergistic and effective in reducing structural
      violence.

PMID- 22382191
TI  - An aetiological & clinicopathological study on cutaneous vasculitis.
AB  - BACKGROUND & OBJECTIVES: Cutaneous vasculitis has protean clinical
      manifestations. It may be idiopathic or associated with a spectrum of conditions
      such as infections, drugs, etc. Skin is involved in both small vessel vasculitis
      (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between
      SVV and MVV. The histopathological features may not always relate with the
      clinical lesions. The aim of the present study was to evaluate the aetiological
      factors and clinicopathological association in patients with cutaneous
      vasculitis. METHODS: In this cross-sectional study, detailed history and clinical
      examination were done on patients with biopsy proven cutaneous vasculitis. Two
      skin biopsies were taken from each patient for routine histopathology and direct
      immunofluorescence. RESULTS: Of the 61 patients studied, hypersensitivity
      vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)]
      were the two most common forms. Systemic involvement was seen in 32 (52.45%)
      patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and
      connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most
      common pattern, seen in all the clinically diagnosed patients with SVV (47), and
      in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence
      showed positivity for at least one immunoreactant in 62 per cent of the patients
      and the most common deposit was C3 followed by IgG, IgA and IgM. INTERPRETATION &
      CONCLUSIONS: Majority of our patients with cutaneous vasculitis were idiopathic.
      Histologically, SVV was seen in most of our patients. No association was seen
      between history of drug intake and tissue eosinophilia and also between
      histologically severe vasculitis and clinical severity. The presence of
      immunoreactant IgA was not specific for HSP.

PMID- 22382192
TI  - Molecular description of plasmid-mediated AmpC beta-lactamases among nosocomial
      isolates of Escherichia coli & Klebsiella pneumoniae from six different hospitals
      in India.
AB  - BACKGROUND & OBJECTIVES: Plasmid mediated AmpC beta-lactamase (PMABL) resistance
      in Escherichia coli and Klebsiella spp. is an emerging problem worldwide.
      Phenotypic methods are commonly used for detection of PMABL production in Gram
      negative isolates, but molecular data about the prevalence of plasmid-mediated
      AmpC-type resistance at the national level are needed. Hence, a prospective study
      was undertaken to determine the occurrence of PMABL gene and its types among
      clinical isolates of E. coli and K. pneumoniae obtained from six different
      hospitals in India. METHODS: A total of 241 nosocomial isolates of K. pneumoniae
      (n=109) and E.coli (n=132) from six geographically distant hospitals in India
      were included. These were screened for cefoxitin resistance. AmpC disk test and
      modified three dimensional extraction test were used for phenotypic detection of
      PMABL production. Molecular types were determined by a multiplex PCR. RESULTS:
      Among the 241 isolates, 187 (77.5%) were found to be cefoxitin resistant (K.
      pneumoniae n=83, E. coli n=104). AmpC activity was detectable in 153 (63.4%)
      isolates, (K. pneumoniae n=69, E. coli n=84). By PCR, the plasmid encoded AmpC
      genes were found in 92 (38.1%) isolates and the molecular types of the genes
      detected predominantly were DHA, CIT followed by MOX and ACC types.
      INTERPRETATION & CONCLUSIONS: A high percentage of plasmid-encoded AmpC enzymes
      was noted in E. coli and K. pneumonia isolates obtained from different parts of
      the country. Phenotypic methods alone may not reflect the true number of PMABL
      producers. Genotypic methods need to be employed in national surveillance
      studies.

PMID- 22382193
TI  - Mosquito biting activity on humans & detection of Plasmodium falciparum infection
      in Anopheles stephensi in Goa, India.
AB  - BACKGROUND & OBJECTIVES: Knowledge of the bionomics of mosquitoes, especially of
      disease vectors, is essential to plan appropriate vector avoidance and control
      strategies. Information on biting activity of vectors during the night hours in
      different seasons is important for choosing personal protection measures. This
      study was carried out to find out the composition of mosquito fauna biting on
      humans and seasonal biting trends in Goa, India. METHODS: Biting activities of
      all mosquitoes including vectors were studied from 1800 to 0600 h during 85
      nights using human volunteers in 14 different localities of three distinct
      ecotypes in Goa. Seasonal biting trends of vector species were analysed and
      compared. Seasonal biting periodicity during different phases of night was also
      studied using William's mean. RESULTS: A total of 4,191 mosquitoes of five genera
      and 23 species were collected. Ten species belonged to Anopheles, eight to Culex,
      three to Aedes and one each to Mansonia and Armigeres. Eleven vector species had
      human hosts, including malaria vectors Anopheles stephensi (1.3%), An.
      fluviatilis (1.8%), and An. culicifacies (0.76%); filariasis vectors Culex
      quinquefasciatus (40.8%) and Mansonia uniformis (1.8%); Japanese encephalitis
      vectors Cx. tritaeniorhynchus (17.4%), Cx. vishnui (7.7%), Cx. pseudovishnui
      (0.1%), and Cx. gelidus (2.4%); and dengue and chikungunya vectors Aedes
      albopictus (0.9%) and Ae. aegypti (0.6%). Two An. stephensi of the total 831
      female anophelines, were found positive for P. falciparum sporozoites. The
      entomological inoculation rate (EIR) of P. falciparum was 18.1 and 2.35 for
      Panaji city and Goa, respectively. INTERPRETATION & CONCLUSIONS: Most of the
      mosquito vector species were collected in all seasons and throughout the
      scotophase. Biting rates of different vector species differed during different
      phases of night and seasons. Personal protection methods could be used to stop
      vector-host contact.

PMID- 22382194
TI  - Association of TNF-alpha with insulin resistance in type 2 diabetes mellitus.
AB  - BACKGROUND & OBJECTIVES: TNF-alpha is an adipocytokine that has been implicated
      in the development of insulin resistance. Dysregulation of TNF-alpha production
      has been implicated in a variety of human diseases including type 2 diabetes
      mellitus. We aimed to find out the association of TNF-alpha levels with insulin
      resistance, body mass index and waist hip ratio; and to elicit its role with
      respect to duration of the disease, if any. METHODS: 50 type-2 diabetic patients
      attending Narayana Medical Hospital, Nellore, were studied. Body mass index and
      Waist hip ratio were calculated. Homeostasis model assessment method was used to
      calculate insulin resistance (HOMA IR) and per cent beta cell function (HOMA B).
      Insulin was estimated by chemiluminescence method and TNF-alpha by ELISA method.
      The subjects were arbitrarily categorized into three groups based on duration of
      diabetes. Group 1 included subjects with diabetes of less than 5 yr duration,
      group 2 included diabetics of 6-10 yr duration and group 3 greater than 10 yr
      duration. RESULTS: Our study revealed a significant correlation between TNF-alpha
      levels and BMI (P=0.006), the correlation being stronger in males when compared
      to females. A significant correlation was found between per cent beta cell
      function and TNF-alpha (P=0.008). TNF-alpha correlated significantly with HOMA
      IR, HOMA B and insulin, in group 2 diabetes. INTERPRETATION & CONCLUSIONS: Our
      results suggest the possible role of TNF-alpha in the pathogenesis of type-2
      diabetes mellitus and the importance of reducing obesity to prevent elevated
      levels of the cytokine and related complications.

PMID- 22382195
TI  - Disappearance of a deadly disease acute hepatomyoencephalopathy syndrome from
      Saharanpur.

PMID- 22382196
TI  - Streptococcus pyogenes pharyngitis & impetigo in a rural area of Panchkula
      district in Haryana, India.

PMID- 22382197
TI  - Methodological errors in screening of Yq microdeletion in Iranian azoospermic
      men.

PMID- 22382198
TI  - Morphea in adults and children cohort II: patients with morphea experience delay
      in diagnosis and large variation in treatment.
AB  - BACKGROUND: Little is known about the diagnosis, evaluation, and therapy of
      morphea (localized scleroderma) in the United States. Delays in diagnosis and
      initiation of appropriate therapy, if present, may negatively affect patient
      care. Further, this gap in knowledge hinders planning for clinical trials and
      therapeutic guidelines. The morphea in adults and children (MAC) cohort is
      designed to address this gap. OBJECTIVE: We sought to determine the duration
      between morphea onset and diagnosis, specialty of the diagnosing provider, and
      initial evaluation and therapy in the MAC cohort. METHODS: This was a cross
      sectional survey of the inception cohort of the MAC study. RESULTS: In all, 63%
      (n = 141 of 224) of patients were given the diagnosis more than 6 months after
      onset. Dermatologists diagnosed and treated the majority of patients (83.5%, n =
      187). Rheumatologists diagnosed and treated the more severe forms of morphea
      (linear and generalized). The most commonly prescribed therapy was topical
      corticosteroids (63%). Dermatologists predominantly prescribed topical treatments
      or phototherapy (P < .0001, P = .0018, respectively), even to patients with
      linear and generalized morphea. In contrast, rheumatologists predominantly
      prescribed systemic immunosuppressives and physical therapy (P < .0001, P =
      .0021, respectively). LIMITATIONS: Referral bias and recall bias may affect
      patterns of evaluation/therapy and ascertainment of disease duration before
      diagnosis. CONCLUSIONS: Patients with morphea experience delay in diagnosis,
      which likely impacts outcome. Therapeutic decision making is largely determined
      by the specialty of the provider rather than disease characteristics and many
      treatments with little or no proven efficacy are used, whereas others with proven
      efficacy are underused. This underscores the need for a collaborative,
      multispecialty approach in designing therapeutic trials and guidelines.

PMID- 22382200
TI  - Congenital syphilis in the 21st century.
AB  - While the prevalence of congenital syphilis continues to be low throughout most
      of the developed world, there has been a slight resurgence of the disease in
      several European countries, including Spain. In this context, we need to become
      more familiar with the signs and symptoms of this disease and consider its
      diagnosis in patients with only mild clinical manifestations. A definitive
      diagnosis may be difficult or even impossible in patients whose diagnostic tests
      reveal low positive titers or inconsistent results. The cornerstone of congenital
      syphilis control is prenatal screening and the treatment of infected mothers with
      penicillin, an effective and economical intervention. Based on a review of the
      literature supplemented by data from our own clinical experience, this article
      provides a detailed description of the clinical manifestations of congenital
      syphilis as well as the various diagnostic methods and treatments available.

PMID- 22382201
TI  - Neoadjuvant chemotherapy, interval debulking surgery or primary surgery in
      ovarian carcinoma FIGO stage IV?
AB  - OBJECTIVES: The aim of this study was to investigate the impact of surgical
      approach, the extent of surgery and chemotherapy on overall survival in patients
      with ovarian carcinoma (OC) stage IV. METHODS: We retrospectively collected
      population-based data from the Norwegian Radium Hospital code registry on the
      diagnosis and surgery of 238 patients diagnosed with OC stage IV from 1996-2005.
      All patients received platinum-based chemotherapy. Surgical approach was
      registered as primary debulking surgery (PDS), interval debulking surgery (IDS)
      and delayed primary surgery (DPS). Surgery level was classified as radical
      surgery (RS), standard surgery (SS) or suboptimal surgery (SUBS). Univariate and
      multivariate analyses identified prognostic factors in PDS, IDS and DPS groups
      and subgroups. RESULTS: There were no differences in overall survival between the
      PDS, IDS and DPS groups. Surgery level was significantly associated with overall
      survival in the whole cohort (p<0.001), the PDS and IDS groups, but not in the
      DPS group. More patients with RS achieved no residual tumour (RT), but overall
      survival was not superior compared to no RT in the SS group. In 66 patients with
      no RT there were no differences in overall survival between those who underwent
      PDS, IDS and DPS. Chemotherapy with platinum/paclitaxel tended to improve
      survival. RT, World Health Organisation (WHO) performance status and histology
      were prognostic factors for overall survival in the whole cohort. CONCLUSION: No
      RT remains the objective, whether PDS, IDS or DPS is performed, and no
      differences in overall survival were found in the three treatment groups.

PMID- 22382202
TI  - Incidence of thyroid hormone therapy in patients treated with sunitinib or
      sorafenib: a cohort study.
AB  - BACKGROUND: Sunitinib and sorafenib can induce serious adverse drug reactions
      (ADR) such as hypothyroidism. However, the incidence has not been reliably
      determined in clinical trials. AIMS: To determine incidence rates (IR) and hazard
      ratios (HR) of thyroid hormone (TH) therapy as a surrogate for sunitinib- and
      sorafenib-induced clinical hypothyroidism. METHODS: A cohort study was performed
      using claims data for prescriptions covering >80% of German pharmacies. Patients
      with a first prescription of sunitinib or sorafenib in the period between June
      2006 and December 2007 were followed until incident prescription of any TH (event
      of interest) or censoring (due to loss to follow-up, discontinuation or switch of
      therapy, prescription of antithyroid drugs or the end of the study). RESULTS: One
      hundred and seventy eight of 1295 sunitinib patients (13.7%) versus 77 of 1214
      sorafenib patients (6.3%) received a TH. IR were 24.2 and 12.1 per 100 person
      years, respectively. Unadjusted HR for TH therapy was 2.0 (95%confidence interval
      (CI) 1.5-2.6) for sunitinib compared to sorafenib and remained significant after
      adjustment for covariates, i.e. type of prescriber, region, insurance status,
      type of insurance fund, and relevant co-medication. CONCLUSIONS: Sunitinib- and
      sorafenib-induced hypothyroidism is a more frequent ADR than currently labelled.
      Furthermore, patients treated with sunitinib have a two-fold increased risk of
      requiring TH therapy compared to sorafenib. Patients being treated with sunitinib
      or sorafenib are, therefore, at risk of thyroid function disturbances and routine
      monitoring both at baseline and throughout treatment with sunitinib and sorafenib
      is justified.

PMID- 22382203
TI  - Polyphenol-rich cranberry juice has a neutral effect on endothelial function but
      decreases the fraction of osteocalcin-expressing endothelial progenitor cells.
AB  - PURPOSE: Cranberry juice (CJ) contains a remarkably high concentration of
      polyphenols, considered to be beneficial for cardiovascular and bone health. The
      current double-blind, randomized study was designed to test whether daily
      consumption of double-strength Ocean Spray light CJ (2 * 230 ml) over 4 months
      has beneficial effects on vascular function and on endothelial progenitor cells
      (EPCs) carrying the osteoblastic marker osteocalcin in particular. METHODS: A
      total of 84 participants (49.5 +/- 16.2 years) with peripheral endothelial
      dysfunction and cardiovascular risk factors were enrolled in this double-blind,
      randomized, controlled trial (69 completed the 4-month protocol-32 in the CJ
      group and 37 in the placebo group, respectively). Vascular responses to reactive
      hyperemia were measured non-invasively by peripheral arterial tonometry
      (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as
      well as osteocalcin, and counted by flow cytometry. RESULTS: Baseline
      characteristics were similar in both groups. The effect of CJ on peripheral
      endothelial function and on circulating EPC counts (CD34(+)/CD133(+)/KDR(+)) did
      not change during the study. A high percentage of EPCs expressed osteocalcin
      (59.4 +/- 35.7%). CJ, as compared to placebo, induced a decrease in the fraction
      of EPCs expressing osteocalcin (-8.64 +/- 48.98 and 19.13 +/- 46.11%,
      respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated
      significantly with the number of EPCs expressing osteocalcin. CONCLUSIONS: The
      study demonstrated that long-term supplementation of polyphenol-rich CJ did not
      improve peripheral endothelial function. However, the decrease in the fraction of
      osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ.

PMID- 22382204
TI  - Application of molecular techniques in the study of natural infection of
      Leishmania infantum vectors and utility of sandfly blood meal digestion for
      epidemiological surveys of leishmaniasis.
AB  - Epidemiological studies on the distribution of leishmaniasis caused by Leishmania
      infantum Nicolle, 1908 (Kinetoplastida: Trypanosomatidae) have been based
      principally on serological surveys of the canine reservoir. This methodology is
      useful due to the facility of sampling, the rapidity in obtaining results, its
      consistency and because it allows the detection of heterogeneous foci of canine
      leishmaniasis (CanL) even in small areas. Other investigations have analysed
      Leishmania parasitism in sandflies (Diptera: Psychodidae: Phlebotominae) by using
      classical dissection techniques. These techniques allow the vector species to be
      incriminated in different foci, although they suffer from being very time
      consuming. Lately, studies in this field are increasingly using molecular
      techniques, which are faster and easier to perform. In the present work, we
      applied a nested-PCR in a study of natural infection of sandflies by Leishmania
      in three isolated farms where serological data on canine leishmaniasis of local
      dogs were also obtained. The analysis allowed the detection of 38.7% of females
      with positive nested-PCR (78%, 18% and 0%, respectively, in the different
      isolated farms). The positive Leishmania DNA samples were genotyped and
      identified as L. infantum. The results of this work provide new data for the
      vectorial capacity of Phlebotomus ariasi in a Pyrenean area, which can be
      considered at risk of becoming a new focus of CanL. The females with positive
      nested-PCR displayed blood in the midgut at different degrees of digestion,
      and/or were gravid. According to the multivariate logistic regression analysis,
      the risk of nested-PCR-positivity increased significantly with the degree of
      blood digestion (OR = 1.3; P value = 0.025). The Phlebotomus species and the
      presence of eggs were not statistically associated with nested-PCR positivity (P
      value of >0.05). The correlation of positive nested-PCR results with the presence
      of seropositive dogs in the farm confirms the utility of this technique in the
      study of the distribution and intensity of leishmaniasis foci. Also, the
      importance of sandfly blood-meal digestion for epidemiological surveys of
      leishmaniasis foci has been demonstrated.

PMID- 22382206
TI  - Synthesis and structures of cyclic gold complexes containing diphosphine ligands
      and luminescent properties of the high nuclearity species.
AB  - A mixture of cyclic gold(I) complexes [Au(2)(MU-cis-dppen)(2)]X(2) (X = OTf 1,
      PF(6)3) and [Au(cis-dppen)(2)]X (X = OTf 2, PF(6)4) is obtained from the reaction
      of [Au(tht)(2)]X (tht = tetrahydrothiophene) with one equivalent of cis-dppen
      [dppen = 1,2-bis(diphenylphosphino)ethylene]. The analogous reaction with trans
      dppen or dppa [dppa = bis(diphenylphosphino)acetylene] affords the cyclic
      trinuclear [Au(3)(MU-trans-dppen)(3)]X(3) (X = OTf 11, PF(6)12) and tetranuclear
      [Au(4)(MU-dppa)(4)]X(4) (X = OTf 13, PF(6)14, ClO(4)15) gold complexes,
      respectively. Recrystallization of 15 from CH(2)Cl(2)/MeOH yielded a crystal of
      the octanuclear gold cluster [Au(8)Cl(2)(MU-dppa)(4)](ClO(4))(2)16. Attempts to
      prepare dicationic binuclear gold(II) species from the reaction of a mixture of 3
      and 4 with halogens gave a mixture of products, the components of which confirmed
      to be acyclic binuclear gold(I) [Au(2)X(2)(cis-dppen)] (X = I 5, Br 7) and cyclic
      mononuclear gold(III) [AuX(2)(cis-dppen)]PF(6) (X = I 6, Br 8) complexes.
      Complexes 11-14 reveal weak emission in butyronitrile glass at 77 K, but they are
      non-emissive at room temperature. Ab initio modelling was performed to determine
      the charge state of the gold atoms involved. Extensive structural comparisons
      were made to experimental data to benchmark these calculations and rationalize
      the conformations.

PMID- 22382205
TI  - Mosquitocidal properties of Calotropis gigantea (Family: Asclepiadaceae) leaf
      extract and bacterial insecticide, Bacillus thuringiensis, against the mosquito
      vectors.
AB  - Calotropis gigantea leaf extract and Bacillus thuringiensis were tested first to
      fourth-instar larvae and pupae of Anopheles stephensi, Aedes aegypti, and Culex
      quinquefasciatus. The medicinal plants were collected from the area around
      Bharathiar University, Coimbatore, India. Calotropis gigantea leaf was washed
      with tap water and shade-dried at room temperature. An electrical blender
      powdered the dried plant materials (leaves). The powder 500 g of the leaf was
      extracted with 1.5 L of organic solvents of methanol for 8 h using a Soxhlet
      apparatus and filtered. The crude leaf extracts were evaporated to dryness in a
      rotary vacuum evaporator. The plant extract showed larvicidal and pupicidal
      effects after 24 h of exposure; no mortality was observed in the control group.
      For Calotropis gigantea, the median lethal concentration values (LC(50)) observed
      for the larvicidal and pupicidal activities against mosquito vector species
      Anopheles stephensi I to IV larval instars and pupae were 73.77, 89.64, 121.69,
      155.49, and 213.79 ppm; Aedes aegypti values were 92.27, 106.60, 136.48, 164.01,
      and 202.56 ppm; and Culex quinquefasciatus values were 104.66, 127.71, 173.75,
      251.65, and 314.70 ppm, respectively. For B. thuringiensis, the LC(50) values of
      I to IV larval instars and pupae of Anopheles stephensi were 37.24, 45.41, 57.82,
      80.09, and 98.34 ppm; Aedes aegypti values were 42.38, 51.90, 71.02, 96.17, and
      121.59 ppm; and Culex quinquefasciatus values were 55.85, 68.07, 94.11, 113.35,
      and 133.87 ppm, respectively. The study proved that the methanol leaf extract of
      Calotropis gigantea and bacterial insecticide B. thuringiensis has mosquitocidal
      property and was evaluated as target species of mosquito vectors. This is an
      ideal ecofriendly approach for the control of vector control programs.

PMID- 22382207
TI  - Static autoregulation is intact early after severe unilateral brain injury in a
      neonatal Swine model.
AB  - BACKGROUND: Autoregulation is impaired by traumatic brain injury. Cerebral blood
      flow disturbances are spatially heterogeneous, but autoregulation is often
      reported as a global metric. OBJECTIVE: We tested lateralization of
      autoregulatory responses in the neonatal piglet brain during hypotension early
      after unilateral injury. METHODS: Neonatal piglets (5-7 days old) had controlled
      cortical impact (severe, n = 12; moderate, n = 13; sham, n = 13) and recovery for
      6 hours. The lower limit of autoregulation (LLA) and static rate of
      autoregulation (SRoR) were determined for each subject and compared among groups
      and between the ipsilateral and contralateral hemispheres. RESULTS: The LLA was
      not increased by injury (sham, 34 mm Hg [29-39 mm Hg]; moderate injury, 37 mm Hg
      [33-41 mm Hg]; severe injury, 35 mm Hg [32-38 mm Hg]; P = .93, mean [95%
      confidence interval]). SRoR, when measured ipsilateral to injury and above the
      LLA, showed intact autoregulation and was not lower than SRoR in uninjured
      subjects (sham, 0.82 [0.53-1.1]; moderate injury, 1.0 [0.60-1.5]; severe, 0.91
      [0.33-1.5]; P = .44). The average hemispheric LLA difference was 2.7 mm Hg, (95%
      limits of agreement, -7.5 to 7.0; bias, -0.25; Spearman r = 0.73; P < .0001).
      Ipsilateral and contralateral SRoR measurements also showed correlation in the
      injured groups (Spearman r = 0.85, P < .0001). CONCLUSION: LLA was not increased
      by controlled cortical impact, nor did SRoR measurements demonstrate ineffective
      autoregulation when cerebral perfusion pressure was greater than and within 10 mm
      Hg of the LLA. Cerebral perfusion pressure optimization, indicated by
      autoregulation measurements, was significantly similar in the 2 hemispheres
      despite severe unilateral injury.

PMID- 22382208
TI  - Rotterdam computed tomography score as a prognosticator in head-injured patients
      undergoing decompressive craniectomy.
AB  - BACKGROUND: The Rotterdam computed tomography (CT) score was developed for
      prognostic purposes in traumatic brain injury (TBI). OBJECTIVE: To examine the
      prognostic discrimination and prediction of the Rotterdam CT score in the case of
      patients undergoing decompressive craniectomy (DC) for TBI. METHODS: The CT scans
      with the worst findings before DC were scored according to the Rotterdam CT
      classification. Mortality and Glasgow Outcome Scale score at the end of follow-up
      were used as outcome measures. Unfavorable and favorable outcomes were defined by
      a Glasgow Outcome Scale score of 1 to 3 and 4 to 5, respectively. We used binary
      logistic and proportional odds regression for prognostic analyses. RESULTS: The
      relationship between the Rotterdam CT score and prognosis was quantified, and
      higher scores indicated worse patient outcomes. Univariate analysis showed that
      the Rotterdam CT score was significantly associated with mortality (odds ratio:
      3.117, 95% confidence interval: 1.867-5.386; P < .001) and unfavorable outcomes
      (odds ratio: 2.612, 95% confidence interval: 1.733-3.939; P < .001). After
      adjustment for published outcome predictors of TBI in multivariate regression,
      the Rotterdam CT score remained an independent predictor of unfavorable outcomes
      (odds ratio: 1.830, 95% confidence interval: 1.043-3.212; P = .035). CONCLUSION:
      For head-injured patients undergoing DC, the Rotterdam CT score provides great
      prognostic discrimination and is an independent predictor of unfavorable
      outcomes. We suggest that the Rotterdam CT score be included as a prognosticator
      in the overall assessment of clinical condition of TBI patients before DC.

PMID- 22382209
TI  - Rate of postprocedural stroke and death in SAMMPRIS trial-eligible patients
      treated with intracranial angioplasty and/or stent placement in practice.
AB  - BACKGROUND: The SAMMPRIS (Stenting vs Aggressive Medical Management for
      Preventing Recurrent Stroke in Intracranial Stenosis) trial, comparing aggressive
      medical vs stent treatment in patients with symptomatic intracranial stenosis,
      was halted after a 14% stroke and death rate was observed in the stent-treated
      group. OBJECTIVE: To study the 30-day stroke and death rate in intracranial
      angioplasty- and stent-treated patients meeting SAMMPRIS trial eligibility
      criteria. METHODS: A retrospective analysis of 96 patients treated with
      intracranial angioplasty and stent placement at 3 university-affiliated
      institutions was performed. Patients were divided into SAMMPRIS trial eligible
      and ineligible groups based on inclusion and exclusion criteria for the SAMMPRIS
      trial. RESULTS: Sixty-nine patients were determined to be SAMMPRIS eligible and
      27 patients were ineligible. The SAMMPRIS-eligible group was divided into
      angioplasty- and stent-treated subgroups (30 and 39 patients, respectively). The
      overall 30-day postprocedure stroke and death rate was 7.2% in the SAMMPRIS
      eligible group and 7.4% in the SAMMPRIS-ineligible group (P = .97). The 30-day
      postprocedure stroke and death rate was 3.3% in the SAMMPRIS-eligible,
      angioplasty-treated subgroup and 10.2% in the SAMMPRIS-eligible, stent-treated
      subgroup (P = .27). CONCLUSION: The overall 30-day postprocedure stroke and death
      rate in our study was lower in both SAMMPRIS-eligible and -ineligible groups than
      the reported 14% stroke and death rate in the SAMMPRIS trial. We hypothesize that
      a more judicious use of primary angioplasty may be responsible for better
      postprocedure outcomes and should be considered an acceptable treatment in future
      trials.

PMID- 22382210
TI  - Differences in developmental changes in GABAergic response between bushy and
      stellate cells in the rat anteroventral cochlear nucleus.
AB  - Many mammalian central nervous system neuron responses mediated by GABA(A)
      receptors undergo a developmental transition from excitation to inhibition, but
      little is known about the time of this switch in specific cell types in the
      developing anteroventral cochlear nucleus (AVCN). In the present study, bushy and
      stellate cells, two major cell types in the AVCN, were identified according to
      their morphology and electrophysiology. The equilibrium potential of GABA-evoked
      currents (E(GABA)) was examined using the gramicidin-perforated patch-clamp
      technique. We found that the action of GABA in bushy and stellate cells switched
      from predominantly depolarizing to predominantly hyperpolarizing with respect to
      their resting membrane potential (V(rest)) at different postnatal ages. Such a
      switch in the GABA response of bushy cells occurred before the first postnatal
      week, whereas that in stellate cells happened at the end of the second postnatal
      week. Furthermore, we discovered that bushy cells had a more depolarized V(rest)
      than did stellate cells before the second postnatal week; however, the E(GABA) of
      bushy and stellate cells was not significantly different. Thus, the discrepancy
      in the timing of the developmental shift from depolarizing to hyperpolarizing
      GABA responses between bushy and stellate cells may be due to the difference in
      their V(rest), but not due to E(GABA) itself. These results suggest that
      GABAergic inhibition functions earlier in bushy than in stellate cells. In
      contrast, the longer excitatory action of GABA on stellate cells possibly renders
      them more vulnerable than bushy cells to excitotoxic substances during early
      development.

PMID- 22382211
TI  - The global role of kidney transplantation.
AB  - World Kidney Day on March 8 th 2012 provides a chance to reflect on the success
      of kidney transplantation as a therapy for end stage kidney disease that
      surpasses dialysis treatments both for the quality and quantity of life that it
      provides and for its cost effectiveness. Anything that is both cheaper and
      better, but is not actually the dominant therapy, must have other drawbacks that
      prevent replacement of all dialysis treatment by transplantation. The barriers to
      universal transplantation as the therapy for end stage kidney disease include the
      economic limitations which, in some countries place transplantation,
      appropriately, at a lower priority than public health fundamentals such as clean
      water, sanitation and vaccination. Even in high income countries the technical
      challenges of surgery and the consequences of immunosuppression restrict the
      number of suitable recipients, but the major finite restrictions on kidney
      transplantation rates are the shortage of donated organs and the limited medical,
      surgical and nursing workforces with the required expertise. These problems have
      solutions which involve the full range of societal, professional, governmental
      and political environments. World Kidney Day is a call to deliver transplantation
      therapy to the one million people a year who have a right to benefit.

PMID- 22382212
TI  - Prehypertension - time to act.
AB  - The term "prehypertension" defined as systolic blood pressure between 120 and 139
      mmHg and/or diastolic pressures between 80 and 89 mmHg has now gained general
      acceptance. Prehypertension is associated with ~3-fold greater likelihood of
      developing hypertension, and roughly twice the number of cardiovascular events,
      than BP < 120/80 mmHg. When compared with normotensive individuals,
      prehypertensive individuals are more likely to be overweight and obese, to have
      other cardiovascular risk factors, to progress to established hypertension, and
      to experience premature clinical cardiovascular disease. The major unresolved
      issue is the appropriate management of such patients. Lifestyle modification is
      recommended for all patients with prehypertension as it effectively reduces rate
      of cardiovascular events. Presently pharmacological therapy is indicated for some
      patients with prehypertension who have specific comorbidities, including diabetes
      mellitus, chronic kidney disease, and coronary artery disease.

PMID- 22382213
TI  - Transplantation with positive complement-dependent microcytotoxicity crossmatch
      in contemporary kidney transplantation: Practice patterns and associated
      outcomes.
AB  - We analyzed clinical factors and graft survival associated with complement
      dependent microcytotoxicity (CDC) crossmatch (XM) positive (+) kidney transplants
      in 1995 to 2009 United Network of Sharing (UNOS) registry data. CDCXM negative (
      ) transplants were selected from centers and years in which at least one CDCXM+
      transplant was performed at a given center in a given year. CDCXM+ and CDCXM-
      results were compared with bivariate and multivariate survival analysis. Our
      observations are as follows: (1) The risk of graft loss with CDCXM+ vs. CDCXM-
      results was markedly lower than the risk observed historically, e.g., living
      donor (LD)-CDCXM+ absolute all-cause graft survival reductions were 0.7% at 24
      hours (P=0.007), 2.9% at one year (P <0.0001), 3.7% at five years (P<0.0001);
      deceased donor (DD)-CDCXM+ absolute graft survival reductions were 0.7% at 24
      hours (P=0.02), 3.5% at one year (P <0.0001), 2.7% at five years (P=0.0009). On
      covariate adjustment, the only significant association of CDCXM+ vs. CDCXM-
      results was with one-year graft loss risk: LD aHR 1.44 (95% CI 1.05-1.96), DD aHR
      1.33 (CI 1.10-1.61). (2) CDCXM+ transplantation was more commonly performed among
      groups disadvantaged with respect to transplant access, including sensitized,
      previously transplanted women and black recipients. (3) In CDCXM+ recipients,
      there was a high percentage of flow cytometry (FC) XM- and autoXM+ results. After
      removing these groups, outcomes with CDCXM+ results were relatively good. (4)
      CDCXM+/FCXM+ vs. CDCXM-/FCXM- graft loss risk was observed only in LD recipients
      transplanted at centers performing fewer than 10 such transplants during the
      study period: 11.0% reduction (P<0.0001) and aHR of 2.86 (CI 1.18-6.94) at one
      year; 14.7% reduction (P<0.0001) and aHR of 1.77 (CI 0.88-3.58) at five years.
      Although using CDCXM+ as a contraindication to transplantation has been
      associated with virtual elimination of hyperacute rejection, the negative effect
      of a CDCXM+ in contemporary practice is relatively small, questioning the value
      of the CDCXM as a standalone test.

PMID- 22382214
TI  - Renal transplantation in allografts with multiple versus single renal arteries.
AB  - Allograft with multiple renal arteries (MRA) is considered to have an increased
      post-transplantation risk due to vascular and urologic complications. The aim of
      this study is to investigate the outcome of living donor kidney transplantation
      using allograft with a single artery and recipients of allografts with multiple
      arteries. Seven hundred and eighteen consecutive adult kidney transplants done
      between 1998 and 2007, with living unrelated kidney donors, were enrolled in this
      retrospective analysis. Data from the group with MRA (n = 60) were compared with
      those from the group with single renal artery (SRA) (n = 658). Delayed graft
      function (DGF) was more frequent in recipients' allografts with more than 2
      arteries when compared with SRA recipients (Odds Ratio: 1.2; 95% CI:1.08-1.9, P =
      0.02), but there was no difference between SRA and allograft with two arteries.
      The incidence of acute rejection (AR) was not statistically greater in recipients
      with MRA. Renal artery stenosis (RAS) occurred more frequently in patients with
      MRA (8.3% vs. 5.9% and P = 0.02), but other vascular complications such as renal
      artery thrombosis and hematoma revealed no differences (P > 0.05). Urologic
      complications such as UVJ obstruction, urinary leakage and ureteropelvic
      obstruction were not statistically different between the groups. The actuarial 1
      year allograft survival rate was comparable in both groups (93.6% vs 96.8%, P =
      0.22). Allografts with more than two arteries were associated with increased DGF
      and RAS, but no surgical or urological complications were detected in our series.
      Our findings demonstrate that renal allograft transplantation with multiple
      arteries could be performed with reasonable complications and acceptable
      outcomes.

PMID- 22382215
TI  - Prevalence of sleep apnea and excessive day time sleepiness in patients with end
      stage renal disease on dialysis.
AB  - Sleep apnea (SA) and excessive daytime sleepiness (EDS) are common sleep
      disorders among patients with end-stage renal disease (ESRD). This cross
      sectional study, carried out in two dialysis centers in Saudi Arabia, assessed
      the prevalence of sleep apnea and sleepiness in Saudi patients with ESRD who are
      on maintenance dialysis with either peritoneal or hemodialysis. We used
      questionnaires to assess the prevalence of SA and EDS. The association between
      sleep apnea, EDS, and other sleep disorders, the underlying causes of renal
      failure, and other demographic data were also examined. Among 227 enrolled
      patients, the mean patient age was 55.7 years +/- 17.2 years; 53.7% were male,
      and 46.3% were female. The overall prevalence of SA as defined by the Berlin
      questionnaire (BQ) was 37% in males and 34% in females, which was not a
      statistically significant difference (P = 0.459). Sleep apnea was significantly
      associated with age, neck size, afternoon and evening hemodialysis shift,
      obesity, diabetes, and hypertension (P-values, 0.001, 0.029, < 0.0001, < 0.0001,
      < 0.008, 0.002, and < 0.001, respectively). Sleep apnea was also significantly
      associated with other sleep disorders such as restless leg syndrome, insomnia,
      habitual snoring, and EDS (P-values, < 0.001, < 0.001, < 0.001, and < 0.001,
      respectively). The prevalence of EDS was 44%, and EDS was significantly more
      prevalent in patients undergoing peritoneal dialysis (P < 0.001); it was also
      associated with older age, diabetes mellitus, and other sleep disorders. SA and
      EDS are common in dialysis patients and are significantly associated with other
      sleep disorders.

PMID- 22382217
TI  - Assessment of immune status in relation to vitamin D levels in children on
      regular hemodialysis.
AB  - The two most common causes of death in patients with chronic kidney disease (CKD)
      are cardiovascular diseases and infections, and both have been linked to impaired
      vitamin D levels and dysregulated immune response. The aim of this work is to
      study the relation between vitamin D levels in children with end-stage renal
      disease (ESRD) on regular hemodialysis (HD) and their immune status. This case
      control study was conducted at the Nephrology Unit, Department of Pediatrics, the
      Zagazig University Hospital, from April 2010 to August 2010. We studied 27
      children with ESRD on regular HD (group-A) whose mean age was 8 +/- 1.3 years;
      there were 15 males and 12 females. The study patients were divided into two
      groups depending on the degree of vitamin D deficiency; group-A1 had 12 patients,
      all of whom had vitamin D deficiency defined as serum concentration of 25-hydroxy
      vitamin D3 [25(OH) D3] of 15-30 ng/mL. Group-A2 had 15 patients with more severe
      vitamin D deficiency (<15 ng/mL). Twenty healthy age- and sex-matched children
      served as the control group (group-B); their mean age was 7.8 +/- 1.6 years and
      they included 12 males and eight females. All subjects underwent thorough history
      taking, clinical examination and the following investigations: complete blood
      count, lymphocyte count, blood urea, serum creatinine, total serum calcium,
      ionized calcium, serum phosphorus, plasma 25(OH)D3, intact para-thormone (iPTH),
      serum interleukin-10 (IL-10) and soluble IL-2 receptor (SIL-2R). We found that
      the vitamin D level was significantly lower in the patient group (group-A) than
      in the control-group (group-B). The IL-10 level was significantly lower in group
      A than in group-B, and the SIL-2R level was significantly higher in group-A than
      in group-B. We found a significant positive correlation between serum 25(OH)D3
      levels and serum IL-10, while there was a negative correlation between 25(OH)D3
      levels and SIL-2R; this correlation was not significant. Our findings suggest
      that 25(OH)D3 levels affect the immune state in patients through their effect on
      both limbs of immunity, the anti-inflammatory and the pro-inflammatory, but the
      effect was higher on the anti-inflammatory IL-10. We conclude that the serum
      levels of vitamin D are lower in children with ESRD than in age-matched controls,
      and that it is significantly positively related to the anti-inflammatory IL-10
      and negatively related to the pro-inflammatory SIL-2R. Further studies are
      required to throw more light on the role of vitamin D supplementation in children
      with ESRD in maintaining immune balance.

PMID- 22382216
TI  - Cardiovascular disease in patients with end-stage renal disease on hemodialysis
      in a developing country.
AB  - Cardiovascular disease is the main cause of death among patients with end-stage
      renal disease (ESRD). The present study was undertaken to identify the main
      cardiovascular diseases and their risk factors in 160 patients with ESRD on
      hemodialysis (HD) in Brazil. Their mean age was 47 +/- 39 years. The main risk
      factors for cardiovascular diseases were arterial hypertension (89.4%),
      dyslipidemia (78.3%), low high-density lipoprotein levels (84.2%) and low
      physical activity (64.1%). Family history of coronary insufficiency and high low
      density lipoprotein levels were significantly associated with coronary artery
      disease (P = 0.005 and P = 0.029, respectively). Sedentary life style, diabetes
      mellitus, secondary hyperparathyroidism and hyperglycemia also showed a
      significant association with the underlying vascular disease (P = 0.017, P =
      0.039, P = 0.037 and P = 0.030, respectively). Hypercalcemia, hypertension and
      black race were factors significantly associated with left ventricular systolic
      dysfunction (P = 0.01, P = 0.0013 and P = 0.024, respectively). Our study shows
      that the most prevalent cardiovascular diseases in patients with ESRD were left
      ventricular hypertrophy, atherosclerotic disease, valvular disease and coronary
      artery disease. Hypertension and dyslipidemia were the common risk factors
      associated with cardiovascular diseases. The present study was undertaken to
      identify the main cardiovascular diseases and their risk factors in 160 patients
      with ESRD on HD in a single center in Brazil.

PMID- 22382218
TI  - Evaluation of lipid peroxidation and erythrocyte glutathione peroxidase and
      superoxide dismutase in hemodialysis patients.
AB  - Oxidative stress often occurs in chronic hemodialysis (HD). The aim of the
      present study was to determine plasma malondialdehyde (MDA) level for lipid
      peroxidation product and erythrocyte superoxide dismutase (SOD) and glutathione
      peroxidase (GPx) activities as enzymatic antioxidants. Thirty-one HD patients
      (aged 50.3 +/- 14.9 years) who were dialyzed three times per week and 31 healthy
      subjects (aged 47.8 +/- 13.9 years) were enrolled. The results showed lower
      enzymatic antioxidants activity (GPx, SOD) and higher MDA levels in comparison
      with control subjects. In addition, SOD and GPx activities significantly
      decreased and MDA increased after HD. We also found that there was a
      significantly negative correlation between SOD and GPx with MDA. The results
      suggest that elevated level of plasma MDA and reduced activities of SOD and GPx
      can be caused oxidative stress, which may play a critical role in HD
      complications.

PMID- 22382219
TI  - A randomized trial of saline hydration to prevent contrast-induced nephropathy in
      patients on regular captopril or furosemide therapy undergoing percutaneous
      coronary intervention.
AB  - Contrast-induced nephropathy (CIN) is characterized by acute deterioration of
      renal function that occurs after parenteral administration of contrast media in
      the absence of other causes. Although no definite proof has been obtained yet,
      the risk of diuretics or angiotensin-converting enzyme inhibitors (ACEI) to
      exacerbate CIN has been reported because of their effects on renal perfusion.
      This study was conducted to assess the protective effect of hydration alone in
      the prevention of CIN after percutaneous coronary intervention (PCI) in patients
      on diuretics or ACEI. This randomized clinical trial was conducted at the Chamran
      Hospital, Isfahan University of Medical Sciences, Iran, during the years 2006
      2007. The study patients were divided into four groups, each group containing 60
      patients. Patients in groups A and B were on regular treatment with ACEI
      (captopril) and patients in groups C and D were on regular diuretic (furosemide)
      therapy. About 36 h before PCI, captopril in group A and furosemide in group C
      were discontinued. The serum creatinine (Cr) levels were measured at the time of
      performing PCI and 24 h and 48 h after PCI in all patients. All patients received
      1 mL/kg/h normal saline (0.9%) 12 h before and 24 h after PCI. The occurrence of
      CIN after PCI was diagnosed based on the following formula: Cr level after PCI -
      Cr level before PCI. If this value was greater than 0.5 mg/dL, it was coded as
      one and if the value was less than 0.5 mg/dL, it was coded as zero. The mean
      difference was analyzed and compared among the four groups by the ANOVA test.
      Three patients (5%) in group A, two patients (3.3%) in group B, two patients
      (3.3%) in group C and one patient (1.6%) in group D had a >0.5 mg/dL difference
      in serum Cr. The difference seen between these groups was not statistically
      significant (P > 0.05). This study shows that although furosemide and captopril
      can exacerbate CIN by impairment of renal perfusion, this can be prevented by
      hydration and discontinuation of furosemide and captopril may not be required.

PMID- 22382220
TI  - Evaluation of high sensitivity C-reactive protein and glycated hemoglobin levels
      in diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is one of the major long-term complications of diabetes
      mellitus (DM). Type 2 DM is frequently associated with an inflammatory status,
      but limited information is available on the relationship between low-grade
      inflammation and DN. The aim of the study is to determine the serum level of high
      sensitivity C-reactive protein (hsCRP) in DN patients and to compare with that of
      normal subjects and to study the association between serum hsCRP levels and
      glycated hemoglobin (HbA1c) levels. Fifty DN patients in the age group of 50- 60
      years with more than ten years of duration of diabetes were recruited for this
      study and 25 age-and sex-matched healthy subjects were included in this study as
      controls. Serum hsCRP levels were measured by turbidometry method. There was a
      statistically significant increase in serum hsCRP levels in DN cases as compared
      to normal controls. The hsCRP levels showed a positive correlation with HbA1c in
      DN. These results suggest that estimation of serum hsCRP levels and aiming at
      good glycemic control help in early intervention and prevention of further com
      plications in diabetic patients.

PMID- 22382221
TI  - Assessment of nitrogen radicals and their scavenging activity in patients with
      end-stage renal failure.
AB  - Reactive oxygen species are implicated in cardiovascular disease in patients with
      chronic renal failure (CRF). This study is aimed to assess the nitrogen radicals
      in patients with end-stage renal failure (ESRF) referred for peritoneal dialysis.
      A total of 36 patients with estimated creatinine clearance <= 15 mL/min were
      recruited from the Dialysis Unit at Al-Yarmouk Teaching Hospital in Baghdad, Iraq
      during 2009, and enrolled into the study. The main causes of CRF were
      hypertension and diabetes mellitus. The median levels of serum nitric oxide and
      peroxynitrite were 300 and 152 MUmol, respectively. Nitric oxide was not detected
      in the sera of 10 patients. The sera of 12 patients showed ability to scavenge in
      vitro, the nitric oxide released by sodium nitroprusside. Significant inverse
      correlation was found between serum peroxynitrite and either systolic (r = 
      0.402) or diastolic (r = -0.387) blood pressure. Our study shows that production
      of nitrogen radicals is enhanced in ESRF and it is accompanied by limited
      activity of scavenging nitric oxide.

PMID- 22382222
TI  - Acute renal failure in falciparum malaria: clinical characteristics,
      demonstration of oxidative stress, and prognostication.
AB  - In this prospective study, we aimed to assess the clinical characteristics of
      acute renal failure (ARF), determine oxidative stress, as well as to predict the
      outcome in patients with severe falciparum malaria (FM). The study included a
      total of 75 subjects; there were 25 adult patients with acute severe FM and ARF,
      25 adult patients with uncomplicated FM without ARF, and 25 age- and sex-matched
      healthy subjects who served as controls. In patients with severe FM and ARF (n =
      25), renal failure was non-oliguric in 28% and oliguric in 72%. The average
      duration of renal failure was 10.53 +/- 4.0 days. Sixty percent recovered and 40%
      died. All patients with non-oliguric presentation recovered. The mean serum
      malondialdehyde (MDA) levels were 0.82 +/- 0.43 MUmol/L, 2.97 +/- 1.11 MUmol/L,
      and 6.86 +/- 2.62 MUmol/L, respectively, in healthy controls, in patients with
      uncomplicated FM, and in those with severe FM with ARF. The Acute Physiology Age
      and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure
      Assessment (SOFA) score, and the Acute Tubular Necrosis-Individual Severity Index
      (ATN-ISI) score were all significantly higher in the expired group (19 +/- 5.49)
      when compared to the survivor group (14.4 +/- 3.15) (P = 0.014). Kaplan-Meier
      survival analysis showed that survival was low in patients with delayed
      hospitalization and longer duration of symptoms. Also, we observed a high
      occurrence of acute respiratory distress syndrome and central nervous system
      involvement among the patients who expired.

PMID- 22382223
TI  - Clinical features and outcomes of ANCA-associated renal vasculitis.
AB  - To determine the patterns and outcomes of the pauci-immune vasculitis in the
      nephrology department at hospital La Conception in Marseille, we conducted a
      retrospective study including all patients with diagnosis of pauci-immune renal
      vasculitis between January 1, 2000 and December 31, 2007. Among 33 cases, 25 were
      diagnosed as Wegener granulomatosis (WG), seven as microscopic polyangitis (MPA)
      and one as Churg-Strauss syndrome (SCS). The median age of the patients was 57.7
      years and the sex-ratio (M/F) was 1.6. The visceral manifestations included
      kidneys (100% of patients), lungs (75%), ENT (52% of WG), and nervous system (57%
      of MPA). The mean serum creatinine at admission was 3.3 mg/dL. Renal biopsies
      revealed a pauci-immune crescentic gromerulonephritis in 96% of the cases. Two
      patients with WG received plasmapheresis and seven patients required emergency
      hemodialysis. Induction therapy comprised cyclophosphamide IV and
      corticosteroids, while maintenance therapy included azathioprine for the majority
      of patients. Eighty four percent of the patients experienced complete remission
      after induction therapy. During maintenance therapy relapses were more frequent
      among patients with MPA (28%) compared to WG cases (12%). After 35 months of
      follow-up, eight patients ended on chronic hemodialysis, and five patients died.
      ANCA associated vasculitis are frequent in our patients. Long-term outcomes are
      relatively good despite a mortality rate of 15% and 25% of the patients entering
      dialysis after three years of follow-up.

PMID- 22382224
TI  - Evaluation of the effects of simvastatin in reduction of panel-reactive antibody
      (PRA) levels in patients with end-stage renal disease awaiting renal
      transplantation.
AB  - This study was undertaken to assess the effect of simvastatin in the reduction of
      panel-reactive antibody (PRA) levels in patients with end-stage renal disease
      (ESRD) awaiting renal transplantation. During the 1-year period from September
      2007 to August 2008, 60 ESRD patients with PRA levels more than 30% were enrolled
      into the study. Each patient was given oral simvastatin 10 mg/day as the initial
      dose. After one month, in those patients who did not respond, the dose was
      increased to 20 mg/day. Again, at the end of two months, if there was no
      response, the dose was further raised to 40 mg/day of simvastatin. The
      appropriate response to the treatment was defined as serum PRA levels getting
      reduced to less than 30%. Among the 60 patients who were enrolled in the study,
      three cases were excluded due to side-effects of the drug and 57 patients
      remained in our study. The mean age was 42.8 +/- 28.2 years (range 18-75). Among
      these, 34 (59.6%) were females. Before the study, the PRA levels were between 30
      and 100 (mean +/- SD: 60.4% +/- 20%). After the administration of simvastatin, a
      significant decrease in PRA levels was seen in our patients (P < 0.0001). In
      patients who had baseline PRA less than 40%, the PRA dropped to below 30% in
      69.2% of the cases with 10 mg simvastatin. In those who had baseline PRA more
      than 40%, a similar reduction was seen only in 15.9% of the cases. However, in
      those who did not respond initially to 10 mg of simvastatin, statistically
      significant reductions were seen after the administration of 20 mg and, if
      needed, 40 mg of simvastatin (P = 0.001). In conclusion, simvastatin can be a
      useful drug in ESRD patients to lower the PRA levels.

PMID- 22382225
TI  - Ambulatory blood pressure monitoring in children and adolescents with type-1
      diabetes mellitus and its relation to diabetic control and microalbuminuria.
AB  - Diabetes mellitus (DM) is now considered as the major cause of end-stage kidney
      failure, and hypertension (HTN) is one of the main determinants of progression of
      renal disease. The aim of this study was to assess the role of blood pressure
      (BP) by ambulatory blood pressure monitoring (ABPM) in children and adolescents
      with type-1 DM and its correlation with micro-albuminuria (MA) and diabetic
      control. Eighty-one patients with type-1 DM (mean age 13 +/- 4 years), whose
      duration of DM was at least two years, were enrolled in this study. The
      prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%.
      The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN
      11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN
      30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were
      33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4%
      had masked HTN, and 3.7% had white coat HTN. The pre-valence of MA was 34.6% and
      that of abnormal HbA 1 c was 82.7%. There was no correlation between HTN and both
      MA and HbA 1 c; also, no correlation was found between the duration of diabetes
      and HbA 1 c. Moreover, no significant correlation was found between the duration
      of diabetes and MA (P = 0.080). Despite the high prevalence of abnormal BP
      profile among diabetic children, prospective longitudinal studies considering the
      other major risk factors, particularly genetic factors, which have an impact on
      the progression to diabetic nephropathy, are recommended.

PMID- 22382226
TI  - Frequency of Chlamydia trachomatis among male patients with urethritis in
      northeast of Iran detected by polymerase chain reaction.
AB  - Planning for appropriate preventive measures against Chlamydia trachomatis, a
      common cause of sexually transmitted disease, requires knowledge of prevalence of
      infection so that interventions can be targeted in a cost-effective manner. This
      study was performed on 178 male patients presenting with urethritis in the
      Mashhad province to determine the prevalence of chlamydial infection in Northeast
      Iran. A cotton swab and first voided urine specimen were collected according to
      standard procedures. Polymerase chain reaction (PCR) tests were used for the
      detection of C. trachomatis in the specimens collected and the results were
      analyzed using SPSS program. Results showed that 10.6% of male patients in this
      group were infected with C. trachomatis. This study provides strong evidence that
      prevalence of Chlamydia in the Northeast Iran is high and suggests that Chlamydia
      screening as a routine part of STD investigations is highly necessary in this
      area.

PMID- 22382227
TI  - Peritonitis caused by Mycobacterium abscesses in patients on continuous
      ambulatory peritoneal dialysis.
AB  - Nontuberculous mycobacteria are an uncommon cause of peritonitis in patients
      undergoing continuous ambulatory peritoneal dialysis. We report two cases of
      peritonitis caused by Mycobacterium abscesses from a single center, which were
      successfully treated. In endemic areas of tuberculosis, Zeil Neilsen staining
      should be part of the initial evaluation to allow early detection. Treatment
      requires removal of Tenckhoff catheter and second-line antibiotics until cultures
      become negative.

PMID- 22382228
TI  - Joubert syndrome presenting as unilateral dysplastic kidney, hypotonia, and
      respiratory problem.
AB  - An 8-month-old girl with a history of asphyxia and respiratory distress
      immediately after birth was hospitalized at her fourth month of age with the
      diagnosis of kidney infection and it was revealed that she had a unilateral
      multicystic dysplastic kidney. In recent admission, she presented to emergency
      room with fever, hyperpnea, and apnea. In appearance, she was a hypotonic girl
      with broad forehead, hypertelorism, depressed nasal bridge and bitemporal
      regions, rapid vertical and horizontal nystagmus, and open mouth with salivation.
      In spite of normal physical growth, she had delayed developmental milestones.
      Blood gas O 2 saturation dropped after she received phenobarbital. Her urinary
      and blood tests were normal; however, her cranial magnetic resonance imaging
      (MRI) revealed vermis agenesis and molar tooth sign. These physical and para
      clinical findings suggested Joubert syndrome.

PMID- 22382229
TI  - A case of exorbitism in association with Wegener's granulomatosis with renal
      involvement.
AB  - Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis involving
      the nose, paranasal sinuses, lungs, and kidneys. Ocular involvement can occur in
      about 50% of cases. There are very few reports of WG with orbital inflammation
      and exorbitism. We report a case of a female patient who presented with
      exorbitism related to orbital inflammation secondary to WG, with renal
      involvement. A 29-year-old woman with a previous history of recurrent pan
      sinusitis presented with bilateral exophthalmos and renal failure with rapidly
      progressive glomerulonephritis. Computed tomography showed extensive bilateral
      soft tissue in the retro-orbital area. Immunologic tests showed the presence of
      type-C anti-neutrophil cytoplasmic antibodies and renal biopsy revealed pauci
      immune crescentic glomerulonephritis. The patient was treated with
      corticosteroids and pulses of cyclophosphamide followed by azathioprine and
      trimethoprim-sulfamethoxazole. After a follow-up of 10 months, the renal outcome
      was favorable with improvement of renal function but there was persistence of
      exorbitism and loss of visual function. Our case suggests that WG should be
      considered in the differential diagnosis of persistent bilateral exophthalmos.
      Prompt recognition of this early manifestation is important for the institution
      of early treatment.

PMID- 22382230
TI  - Rituximab in the treatment of refractory lupus nephritis with vasculitis.
AB  - Dysfunction of the B lymphocyte, an important component of adaptive immunity, is
      thought to be important in the pathogenesis of lupus nephritis (LN). There are
      several novel strategies emerging including B-cell depletion by the monoclonal
      antibodies to B-cell markers, rituximab. We describe an unusual clinical response
      of a 22-year-old Hispanic woman with class IV LN with vasculitis while on
      dialysis to cyclophosphamide (CY) and adjunct rituximab. The patient had a
      history of class III/V LN and was treated with nine months of CY and maintenance
      therapy with mycophenolate mofetil (MMF) for three years. While on MMF, the
      patient developed class IV LN with vasculitis leading to end-stage renal disease
      (ESRD). While the patient was on peritoneal dialysis, the patient was treated
      with two doses of rituximab and six doses of intravenous CY. The patient
      responded to this regimen and recovered kidney function within four months. The
      kidney function remained stable nine months after discontinuing peritoneal
      dialysis.

PMID- 22382231
TI  - Familial prune belly syndrome in a Nigerian family.
AB  - A case of Prune Belly Syndrome in an infant, the second in a middle class family
      with both parents in their late thirties, is presented because of its rarity.
      Constraints in the management are discussed and relevant literature reviewed.
      This is intended to awaken interest and sharpen indices of suspicion that would
      facilitate early diagnosis, enhance management, and mitigate prejudices.

PMID- 22382232
TI  - Diffuse proliferative crescentic lupus nephritis with normal renal function.
AB  - Crescentic nephritis can be a manifestation of Lupus Nephritis. It usually
      presents with rapid deterioration of renal functions over days to weeks with an
      active urinary sediment and confers a poor prognosis. Nephrotic range proteinuria
      is rare in crescentic nephritis. We present an interesting case of (crescentic)
      Diffuse Proliferative Lupus Nephritis (DPLN) with remarkably preserved renal
      function and nephrotic range proteinuria. Also noteworthy was the patient's
      excellent response to immunosuppressive therapy despite the high frequency of
      cellular crescents on biopsy.

PMID- 22382233
TI  - Urofacial syndrome.
AB  - The urofacial syndrome is characterized by functional obstructive uropathy
      associated with an inverted smile. The importance of the subject is that it sheds
      light, not only on the muscles of facial expression, but also on the inheritance
      of voiding disorders and lower urinary tract malformations. We report a 10-year
      old-male patient who had the urofacial syndrome. Early diagnosis of the urofacial
      syndrome is important to avoid upper urinary tract damage and renal failure.

PMID- 22382234
TI  - Neurotoxicity due to cefepime in patients on maintenance hemodialysis.

PMID- 22382235
TI  - The trauma of the thoracic duct is a rare complication of jugular catheterization
      with fistula lymphatico-cutaneous.

PMID- 22382236
TI  - Successful percutaneous continuous ambulatory peritoneal dialysis catheter
      insertion in a patient with past abdominal surgeries.

PMID- 22382237
TI  - Management of obstructive uropathy with cutaneous ureterostomy in posterior
      urethral valve.

PMID- 22382238
TI  - Renal angiomyolipoma.

PMID- 22382239
TI  - Concerns regarding laboratory analysis of urine protein: a brief comment.

PMID- 22382240
TI  - Acute cortical necrosis and collapsing glomerulopathy in an HIV-infected patient:
      a rare clinical scenario.

PMID- 22382241
TI  - Nanotechnology in nephrology.

PMID- 22382242
TI  - Necrotic crescentic glomerulonephritis and IgA nephropathy: Lee-hass
      classification revisited.

PMID- 22382243
TI  - Co-administration of albumin and furosemide in patients with the nephrotic
      syndrome.

PMID- 22382244
TI  - Bilateral renal infarction due to thromboembolism.

PMID- 22382245
TI  - Histopathological pattern of pediatric renal diseases: a study from a university
      hospital in western Saudi Arabia.
AB  - To study the clinical indications and histopathological pattern of renal biopsies
      and renal resection specimens in the pediatric age group (birth to 17 years) in a
      large academic center in western Saudi Arabia. A retrospective review of the
      computerized database of the Pathology Department at King Abdul Aziz University
      Hospital (KAUH) was carried out on the final pathology reports of all children of
      the age of 17 years and below who either had ultrasound-guided renal biopsies or
      partial or total renal resections during the period between January 1995 and
      December 2008. All the specimens were reported by our pathology department. The
      most common clinical indication in the study group (242) is nephrotic syndrome
      (117, 48.3%), followed by systemic lupus erythromatosis for staging (30, 12.4%),
      nephritic syndrome (27, 11.1%) and renal mass for histological diagnosis (17,
      7.0%). The most frequently reported pathological diagnosis was renal
      glomerulopathies, constituting 183 cases (n = 183, 75.6%) of the total number of
      pathology reports reviewed. Primary glomerulopathies were more common (n = 155,
      88.4%) than the secondary ones (n = 28, 11.6%). The second most common pediatric
      renal pathology in this study was renal neoplasms (14, 5.7%). Vascular renal
      diseases and renal glomerulosclerosis ranked as the third pathological diagnosis
      in order of frequency in this study, with ten cases (10, 4.1%). The most common
      clinical indication for renal tissue sampling in this study is nephrotic syndrome
      and the most frequently detected pathology is glomerulonephritis. Larger
      multicentre studies are needed to further study pediatric nephropathies.

PMID- 22382246
TI  - Primary hyperoxaluria type 1 in Tunisian children.
AB  - To determine the clinical, biological, and radiological futures of primary hyper
      oxaluria type 1 in Tunisian children, we retrospectively studied 44 children with
      primary hyper-oxaluria type 1 who were treated in our center from 1995 to 2009.
      The diagnosis was established by quantitative urinary oxalate excretion. In
      patients with renal impairment, the diagnosis was made by infrared spectroscopy
      of stones or kidney biopsies. The male-to-female ratio was 1:2. The median age at
      diagnosis was 5.75 years. About 43% of the patients were diagnosed before the age
      of five years with initial symptoms dominated by uremia. Four patients were
      asymptomatic and diagnosed by sibling screenings of known patients.
      Nephrocalcinosis was present in all the patients; it was cortical in 34%,
      medullary in 32%, and global in 34%. At diagnosis, 12 (27%) children were in end
      stage renal disease. Pyridoxine response, which is defined by a reduction in
      urine oxalate excretion of 60% or more, was obtained in 27% of the cases. In the
      majority of patients, the clinical expression of primary hyperoxaluria type 1 was
      characterized by nephrocalcinosis, urolithiasis, and renal failure; pyridoxine
      sensitivity was associated with better outcome.

PMID- 22382247
TI  - Factors influencing hemodialysis and outcome in severe acute renal failure from
      Ilorin, Nigeria.
AB  - The epidemiology of acute renal failure (ARF) varies between nations and even
      within the same country because of differences in diagnostic criteria, causes,
      mode of presentation, and cost of therapy. To determine the factors influencing
      hemodialysis and outcome of severe ARF in Ilorin, Nigeria, we studied ARF
      patients on hemodialysis in our center between January 1989 and December 2009.
      There were 138 (58 males and 80 females) patients with age range between 18 and
      69 years and a mean of 29.4 +/- 11.9 years. Major etiologies of ARF included
      septicemia, acute glomerulonephritis, septic abortion, herbal remedies, post
      partum bleeding, and gastroenteritis. The mean duration of illness and waiting
      time before dialysis was 11.7 +/- 8.14 days and 3.28 +/- 1.86 days, respectively.
      The mean number of dialysis was 2.24 +/- 1.13 sessions and 89% of the patients
      received a maximum of three sessions before recovery. Hypotension, twitching of
      muscles, and back pains were common intradialysis complications. The factors that
      influenced hemodialysis and outcome were late presentation, severity of ARF, and
      financial constraints. The etiological agents are preventable and treatable
      conditions. The short duration of hospital stay, waiting time before dialysis,
      and total duration of illness influenced the outcome positively. We strongly
      recommend early referral of patients with severe ARF to nephrologists for proper
      management in a bid to reduce mortality from this disease.

PMID- 22382248
TI  - Interstitial nephritis with moderate-to-heavy proteinuria: an unusual
      combination.
AB  - Interstitial nephritis with proteinuria >1 g/day is uncommon and almost always
      the result of drug-induced ATIN with an associated minimal change
      glomerulonephritis (GN). Here, we present a series of five unusual cases of
      interstitial nephritis without GN but with proteinuria >1 g/day, and they were
      identified from renal biopsies done from February 2008 to March 2009. Out of 236
      patients who underwent renal biopsy, only five met the inclusion criteria. Three
      patients presented with edema and two with oliguria, while none had frank
      hematuria, fever, arthralgia, skin rash or history of exposure to nonsteroidal
      antiinflamatory drugs, analgesics, antibiotics, allopurinol, or Chinese herb
      before presentation. Urinalysis revealed hematuria in two patients, pyuria in
      three and nephrotic range proteinuria in two. All had normal complement levels
      and were negative for antinuclear antibodies, Anti-dsDNA antibody, and
      antineutrophil cyto-plasmic antibodies. Clinical diagnosis was nephrotic syndrome
      in two patients, the third had diagnosis of rapidly progressive GN, the fourth
      had HIV associated nephropathy, and the fifth had unexplained advanced renal
      failure. Though three patients had renal dysfunction only one required dialysis.
      Light microscopy of renal biopsies revealed granulomatous interstitial nephritis
      in three patients and small vessel vasculitis in two of them. One patient had
      nongranulomatous interstitial nephritis along with vasculitis. Acute interstitial
      nephritis was the only finding in one patient. In conclusion, patients with
      interstitial nephritis can present with moderate-to-heavy proteinuria probably
      due to cytokine-like permeability increasing factor secreted by inflammatory
      cells in the interstitium.

PMID- 22382249
TI  - Medication prescribing patterns among chronic kidney disease patients in a
      hospital in Malaysia.
AB  - To determine the medication prescribing patterns in hospitalized patients with
      chronic kidney disease (CKD) in a Malaysian hospital, we prospectively studied a
      cohort of 600 patients in two phases with 300 patients in each phase. The first
      phase was carried out from the beginning of February to the end of May 2007, and
      the second phase was from the beginning of March to the end of June 2008.
      Patients with CKD who had an estimated creatinine clearance <= 50 mL/min and were
      older than 18 years were included. A data collection form was used to collect
      data from the patients' medical records and chart review. All systemic
      medications prescribed during hospitalization were included. The patients were
      prescribed 5795 medications. During the first phase, the patients were prescribed
      2814 medication orders of 176 different medications. The prescriptions were 2981
      of 158 medications during the second phase. The mean number of medications in the
      first and second phases was 9.38 +/- 3.63 and 9.94 +/- 3.78 respectively (P-value
      = 0.066). The top five used medications were calcium carbonate, folic
      acid/vitamin B complex, metoprolol, lovastatin, and ferrous sulfate. The most
      commonly used medication classes were mineral supplements, vitamins, antianemic
      preparations, antibacterials, and beta-blocking agents. This study provides an
      overview of prescription practice in a cohort of hospitalized CKD patients and
      indicates possible areas of improvement in prescription practice.

PMID- 22382251
TI  - Screening for aortic abdominal aneurysm in New Zealand.

PMID- 22382250
TI  - Analysis of 88 nephrectomies in a rural tertiary care center of India.
AB  - Nephrectomy is not an uncommon surgery in day-to-day practice of urology. Trauma
      is the most common cause of emergency nephrectomy. On the other hand, elective
      nephrectomy is done for both benign and malignant diseases of the kidney. This
      study has been performed to know the different causes of nephrectomy in a rural,
      tertiary care center of India. In our series, we have studied all the elective
      nephrectomies done in our hospital during a period of eight years. We have
      analyzed 88 cases of nephrectomies regarding their age, sex, laterality of
      disease, and histopathologic report of the nephrectomy specimens. Out of 88
      cases, 61 were males and 27 were females. In our series, 62.5% cases of
      nephrectomies were done for benign causes and 37.5% cases for malignant causes.
      Among the benign causes, neglected pelviureteric junction obstruction was the
      leading cause, followed by calculus disease resulting in obstruction. On the
      other hand, renal cell carcinoma was the most common malignant pathology
      requiring nephrectomy.

PMID- 22382252
TI  - Abdominal aortic aneurysm disease in New Zealand: epidemiology and burden between
      2002 and 2006.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) rupture has a high mortality. Four
      randomised controlled trials indicate significant mortality benefit from
      population screening for AAA. There is a lack of information on the epidemiology
      and burden of AAA disease in New Zealand, necessary to support policy in this
      area. METHODS: A retrospective analysis was conducted on a dataset consisting of
      all AAA deaths and all hospital discharges with a AAA diagnosis between 2002 and
      2006. Analysis by age, sex, ethnicity, and operative status was performed.
      RESULTS: On average, there were 267 elective repairs and 87 emergency repairs
      annually between 2002 and 2006. The operative mortality rate was 35.2% for
      emergency repair, and 6.7% for elective repair.  There were about 236 known AAA
      related deaths annually. Ninety-four percent of AAA deaths between 2002-2006
      occurred in individuals >65 years. The case fatality for females was higher than
      males across every age group. The standardised mortality rate in Maori was twice
      as high as New Zealand Europeans. CONCLUSIONS: This study provides essential
      information to evaluate the appropriateness and feasibility of AAA screening
      here. A population-based prevalence study is recommended, along with further
      investigation of high case fatality in females and high mortality in Maori.

PMID- 22382253
TI  - Funding community medicines by exception: a descriptive epidemiological study
      from New Zealand.
AB  - AIMS: To assess rates of approval and identify factors associated with successful
      applications for funding to the New Zealand Community Exceptional Circumstances
      (CEC) scheme. METHOD: Descriptive quantitative analysis of data in CEC
      applications database. The main outcome was initial application approval rate.
      Analysis included calculation of unadjusted and adjusted associations between
      potential determinants (for example patient age, gender) and outcomes using
      logistic regression analysis. All CEC applications with a decision about approval
      or decline 1 October 2001 to 30 September 2008 were included. RESULTS:
      Application numbers were high, but had reduced since 2001. A small number of
      medicines (11) and indications comprised about a third of the applications to the
      scheme. While some common applications were clearly outside the remit of the
      scheme, many applications were for patients who fitted the scheme's eligibility
      criteria. The overall initial application approval rate was 16% and the renewal
      application approval rate was 88%. Approval rates varied widely by type of
      medicine, therapeutic group and indication. After adjusting for other potential
      determinants there were no statistically significant differences in initial
      approval rates by gender, ethnicity or socioeconomic status of the patient. There
      were however, significant differences in initial application approval by age of
      the patient, type of applicant doctor and by geographical location of the
      applicant doctor. CONCLUSIONS: There was no evidence that gender, ethnicity and
      socioeconomic status of patients were factors associated with successful
      applications. However, applications for younger patients, those made by
      specialists, and those made by applying clinicians from the Auckland District
      Health Board area were more likely to be successful. It is possible that this may
      to some degree be appropriate, but requires further research.

PMID- 22382254
TI  - Blinded randomised controlled study of the effect of a discharge communication
      template on proton pump inhibitor prescribing.
AB  - AIM: To evaluate whether the inclusion of advice in the hospital discharge letter
      regarding published guidelines for the review of PPI therapy can increase the
      number of patients that have documented PPI therapy review, consistent with the
      published guidelines, following hospital discharge. METHOD: Patients on PPIs at
      discharge from hospital were randomised to either have their hospital discharge
      letter completed as per usual practice or to have additional information on PPI
      review included that was aligned to published local guidelines. Patients' GP
      records were reviewed at 3 to 6 months post discharge to determine if a PPI
      review had occurred and if that review adhered to the guidelines. RESULTS:
      Including specific, guideline based, PPI discharge instructions in the hospital
      discharge summary did not significantly increase the number of patients receiving
      post-discharge review consistent with the guidelines. Post discharge only 5/26
      (19%) patients in the control group and 6/25 (24%) in the intervention group had
      their PPI therapy reviewed in accordance with the guidelines. CONCLUSION: We were
      not able to demonstrate a beneficial change in PPI prescribing practice from the
      inclusion of PPI prescribing advice in the discharge letter.

PMID- 22382255
TI  - A review of interferon use in patients with relapsing remitting multiple
      sclerosis in the Canterbury region, New Zealand: 2000-2006.
AB  - We report a retrospective medical chart review of 104 patients resident in
      Canterbury and surrounding districts with relapsing remitting multiple sclerosis
      (RRMS), who received funded interferon-beta between 2000 and 2006. The aim of the
      study was to review relapse rates, Expanded disability status scale (EDSS) scores
      and intravenous methylprednisolone (IVMP) use in the 2-year period before, and
      following, the initiation of interferon-beta therapy. Demographic analysis showed
      that the age at entry, duration of disease and EDSS at entry were each greater
      than in the landmark clinical trials. Relapse rates and usage of IVMP decreased
      when compared to the 2 years prior to treatment.

PMID- 22382256
TI  - Incidental vertebral fractures on computed tomography.
AB  - Vertebral fractures are the most common osteoporotic fracture and predict
      subsequent fracture and mortality. We undertook an audit (Auckland City Hospital,
      Auckland, New Zealand) to determine whether targeted assessment for incidental
      vertebral fractures on computed tomography (CT) examinations of the chest or
      abdomen in older people would detect previously unidentified vertebral fractures.
      In 175 consecutive patients aged >65 years, sagittal images of the spine were
      obtained by reformatting data from CT examinations of the chest or abdomen.
      Vertebral fractures were assessed using a semi-quantitative technique.  The
      prevalence of vertebral fractures was 13%, with 41 vertebral fractures identified
      in 22 patients; 12/22 (55%) had vertebral fracture mentioned in the formal CT
      report, and 2/12 patients with contemporaneous plain films had vertebral fracture
      mentioned in the X-ray report. The vertebral fracture was newly identified in 17
      (77%) patients, but vertebral fracture and osteoporosis were each listed in the
      relevant discharge summary or clinic letter for only 14% of patients, and only
      31% of patients with fracture subsequently received osteoporosis treatment.  In
      summary, assessing sagittal spine images reformatted from CT examinations of the
      chest or abdomen detects previously unidentified vertebral fractures, offering an
      undervalued opportunity to assess fracture risk and intervene with treatments
      that prevent fractures and reduce mortality.

PMID- 22382257
TI  - Predictors of intent to vaccinate against HPV/cervical cancer: a multi-ethnic
      survey of 769 parents in New Zealand.
AB  - AIM: To identify factors predictive of parents' intent to have their daughters'
      receive the HPV/cervical cancer vaccine. METHODS: 3123 questionnaires were
      distributed to parents recruited from 14 socioeconomically diverse schools in
      2008. Survey questions were structured around the health beliefs model. The main
      outcome measure was intent to seek vaccination for daughter(s). RESULTS: A
      quarter of parents completed questionnaires (769/3123). Two-thirds of respondents
      (67%) indicated they would want their daughter(s) to receive the vaccine, with no
      significant differences by ethnicity. Intent to vaccinate was significantly
      associated with having fewer negative views on vaccination (OR 0.47, 95%CI 0.37
      0.59), having adequate information about the vaccine, perceiving HPV infection
      and cervical cancer as serious and likely to occur (OR 1.2, 95%CI 1.05-1.36), and
      considering efficacy and safety of the vaccine important (OR 1.17, 95%CI 1.06
      1.28) (p<0.01). Awareness of HPV-related facts was lowest among Maori and Pacific
      parents (p<0.001). Pacific parents were more likely to have concerns about
      vaccination impacting negatively on girls' sexual behaviour. IMPLICATIONS:
      Strategies will be needed to provide detailed information outlining HPV
      prevalence and consequences, vaccine safety and efficacy to ensure all parents
      and their daughters are adequately informed when deciding on vaccination.

PMID- 22382258
TI  - Cases of cutaneous diphtheria in New Zealand: implications for surveillance and
      management.
AB  - AIM: Diphtheria is an acute bacterial illness caused by toxigenic strains of
      Corynebacterium diphtheriae (C. diphtheriae). We describe two epidemiologically
      linked cases of skin infections from which toxigenic C. diphtheriae was isolated,
      and discuss implications for diphtheria surveillance and management in New
      Zealand. METHOD: A public health investigation was undertaken to identify and
      manage close contacts of the index case. National and international guidelines on
      the surveillance and management of cutaneous diphtheria were reviewed, and data
      on toxigenic C. diphtheriae isolates identified in New Zealand from 1987-2009
      were examined. RESULTS: The index case was an adult male who developed a
      cutaneous infection after being tattooed in Samoa. A wound swab taken from the
      infected tattoo grew a toxigenic strain of C. diphtheriae (var gravis). A
      secondary case of toxigenic cutaneous diphtheria was identified in a household
      contact. Instances of respiratory diphtheria associated with toxigenic cutaneous
      lesions have been reported in the literature. The review of surveillance data
      revealed inconsistencies in the notification of toxigenic strains of C.
      diphtheriae isolated from cutaneous sites. CONCLUSION: These cases are an
      important reminder that diphtheria remains a threat in New Zealand. All cases
      with toxigenic C. diphtheriae isolated from a clinical specimen, regardless of
      the site of infection, should be notified to a Medical Officer of Health.

PMID- 22382259
TI  - Population screening for abdominal aortic aneurysm: evaluating the evidence
      against screening criteria.
AB  - Screening for abdominal aortic aneurysm (AAA) has been initiated in the United
      Kingdom and United States. Screening using abdominal ultrasound scans allows AAAs
      to be detected and electively repaired before rupture. There is currently no
      policy for AAA screening in New Zealand (NZ). We reviewed literature to assess
      current evidence for AAA screening against standard criteria used to evaluate
      population-based screening programmes.  AAA rupture has high mortality, and
      people of Maori ethnicity are disproportionately affected. Abdominal ultrasound
      is a valid screening tool, and elective repair is an effective treatment.
      Screening reduces AAA-related mortality by about 40% in elderly men. However, the
      age and comorbidities of AAA patients means rupture risk has to be weighed
      against elective repair risk. Overtreatment is likely, given most individuals
      with AAA will not experience rupture in their lifetime. AAA screening appears to
      be cost-effective. It is unclear if the health system could support all the
      elements of a AAA screening pathway.  AAA appears to be an appropriate condition
      for which to consider population screening. We recommend research into the
      prevalence of AAA in NZ, the comorbidity profile of individuals with AAA, drivers
      of high mortality among Maori, and acceptability of AAA screening to the New
      Zealand public.

PMID- 22382260
TI  - The NEEDNT Food List: non-essential, energy-dense, nutritionally-deficient foods.
AB  - AIM: To provide a list of non-essential, energy-dense, nutritionally-deficient
      foods in New Zealand (NEEDNT foods) which are usually high in calories and either
      bereft of nutritional benefits or easily replaced with lower calorie, more
      nutritious alternatives. METHODS: The List was compiled using the National Heart
      Foundation and Diabetes New Zealand "Foods to Avoid", "Stop Eating" and "Optional
      Foods" lists and the Canterbury District Health Board "Supermarket Shopping
      Guide". Foods and beverages were included if they contained alcohol, saturated
      fat, added sugar, were prepared using a high fat cooking method or contained a
      large amount of energy relative to their essential nutrient value. As it has no
      energy value, salt was not a criterion for inclusion on the List. RESULTS: Over
      50 potential foods or groups of foods were identified that contained alcohol,
      saturated fat, added sugar, were prepared using a high fat cooking method or
      contained a large amount of energy relative to their essential nutrient value.
      Fifty foods/groups of foods were included on the final list (Table 1).
      CONCLUSIONS: The NEEDNT Food List will be a useful tool for medical practitioners
      and other health professionals working with people wanting to lose weight
      [corrected].

PMID- 22382261
TI  - A case of cutaneous diphtheria in New Zealand.
AB  - We report the case of an adult male who contracted cutaneous diphtheria after
      receiving a tattoo in Samoa. The infection required hospital admission. The
      Regional Public Health Service conducted urgent contact tracing. We review the
      techniques employed in traditional tattooing and highlight the importance of
      considering C. diphtheriae as a causative organism in cutaneous infection
      acquired in the tropics.

PMID- 22382262
TI  - Medical image. Limited systemic sclerosis.

PMID- 22382263
TI  - PHARMAC has no cost-effectiveness threshold.

PMID- 22382264
TI  - The importance of vitamin D: a response to the article by Bolland and colleagues.

PMID- 22382265
TI  - BPAC recertification plan and the Medical Council.

PMID- 22382266
TI  - The ethics of care.

PMID- 22382267
TI  - Relative risk according to the proportion of a population deemed to be at high
      risk after risk factor analysis: a correction.

PMID- 22382268
TI  - Comment on "ACC response on rotator cuff tears".

PMID- 22382269
TI  - Comment on "Under-use of secondary prevention medication" article by Looi and
      colleagues.

PMID- 22382270
TI  - Hands-only CPR.

PMID- 22382271
TI  - Perioperative results in the Canterbury pilot programme of public-funded weight
      loss surgery.

PMID- 22382272
TI  - The Cockroft and Gault formula for estimation of creatinine clearance: a friendly
      deconstruction.
AB  - AIMS: To review the derivation of the Cockroft and Gault formula for estimating
      creatinine clearance from serum creatinine in a historical context. METHOD: The
      derivation described by Cockroft and Gault was reviewed, and an alternative
      formula was sought using the data reported in the paper. RESULTS: Cockroft and
      Gault used 24 hour urine creatinine data expressed as mg/kg body weight and
      mathematical manipulation of a linear regression equation which introduced body
      weight as an independent variable into the formula. This involved a circular
      logic and may have been mathematically invalid. A more logical equation not
      containing body weight was derived from the data. CONCLUSION: The Cockcroft and
      Gault formula has been validated by long usage but the derivation appears
      logically insecure. Nevertheless, its role in estimating renal function at the
      bedside is established.

PMID- 22382273
TI  - Comparison of electromyography and joint moment as indicators of co-contraction.
AB  - Antagonistic muscle activity can impair performance, increase metabolic cost, and
      increase joint stability. Excessive antagonist muscle activity may also cause an
      undesirable increase in joint contact forces in certain populations such as
      persons with knee osteoarthritis. Co-contraction of antagonistic muscles measured
      by electromyography (EMG) is a popular method used to infer muscle forces and
      subsequent joint forces. However, EMG alone cannot completely describe joint
      loads that are experienced. This study compares a co-contraction index from EMG
      to a co-contraction index calculated from simulated muscle moments during gait.
      Co-contraction indices were calculated from nine healthy, able-bodied subjects
      during treadmill walking at self-selected speed. Musculoskeletal simulations that
      tracked experimental kinematics and kinetics were generated for each subject.
      Experimentally measured EMG was used to constrain the model's muscle excitation
      for the vastus lateralis and semimembranosus muscles. Using the model's
      excitations as constrained by EMG, muscle activation and muscle moments were
      calculated. A common co-contraction index (CCI) based on EMG was compared with co
      contraction based on normalized modeled muscle moments (MCCI). While the overall
      patterns were similar, the co-contraction predicted by MCCI was significantly
      lower than CCI. Because a simulation can account for passive muscle forces not
      detected with traditional EMG analysis, MCCI may better reflect physiological
      knee joint loads. Overall, the application of two co-contraction methods provides
      a more complete description of muscle co-contraction and joint loading than
      either method individually.

PMID- 22382274
TI  - The emerging science of BMAA: do cyanobacteria contribute to neurodegenerative
      disease?

PMID- 22382275
TI  - Surveillance programme for multidrug-resistant bacteria in healthcare-associated
      infections: an urban perspective in South Brazil.
AB  - Multidrug-resistant bacteria (MDRB) have emerged as a public health problem and
      the World Health Organization recommends actions to control MDRB in healthcare
      associated infections (HCAIs). This study describes a surveillance programme for
      MDRB in HCAIs at Curitiba, Brazil. MDRB in pneumonia, bloodstream, urinary tract
      and surgical site infections has been surveyed since January 2010. Carbapenem
      resistant Acinetobacter baumannii and third generation resistant Klebsiella
      pneumoniae were the most frequent MDRB in HCAIs. Infection control strategies
      enrolling hospitals and public health have been developed. The data presented
      describe MDRB prevalence and the feasibility of this municipal MDRB surveillance
      programme in Brazil.

PMID- 22382276
TI  - Escherichia coli bacteraemia: how preventable is it?

PMID- 22382277
TI  - Control of bacterial contamination of washbasin taps and output water using
      Ecasol: a one-year study.
AB  - BACKGROUND: Contaminated washbasin taps and output water are an important source
      of bacteria that may cause nosocomial infection. A five-week pretreatment study
      of hot and cold water from 15 washbasin taps at Dublin Dental Hospital showed
      consistently heavy contamination by aerobic heterotrophic bacteria: mean
      bacterial counts of 482.5 [standard deviation (SD) 293] colony-forming units
      (cfu)/mL and 5022 (SD 4322) cfu/mL, respectively. AIM: To minimize microbial
      contamination of washbasin taps and output water in the long term using the
      electrochemically generated, pH-neutral disinfectant, Ecasol. METHODS: Initially,
      the 15,000-L water tank providing cold and hot water to washbasins, calorifiers
      and the distribution network were drained and sediment was removed. The system
      was shock-dosed with Ecasol 100 ppm to eradicate gross contamination and
      biofilms. Thereafter, tank water was automatically maintained at Ecasol 2.5 ppm
      prior to distribution. The microbiological quality of water from five sentinel
      washbasin taps was monitored weekly for 54 weeks using R2A agar. FINDINGS: The
      mean counts for hot, cold, mains and tank water during the 54-week study period
      were 1 (SD 4) cfu/mL, 2 (SD 4) cfu/mL, 205 (SD 160) cfu/mL and 0 cfu/mL,
      respectively. Swab samples of 33/40 taps, each tested on three separate
      occasions, yielded no growth on R2A agar, while five samples yielded <20 cfu/swab
      and two samples yielded >200 cfu/swab. No detrimental effects due to Ecasol were
      observed in the water network. CONCLUSION: Ecasol consistently minimized
      bacterial contamination of washbasin taps and output water in a dental hospital
      setting.

PMID- 22382278
TI  - Violence as a risk factor for postpartum depression in mothers: a meta-analysis.
AB  - The objective of this paper is to examine the association between violence and
      postpartum depression (PPD). The data sources of this study are: Web of Science,
      PubMed, Elsevier, Springer Link were examined from their start date through
      July1, 2011. "Violence", "domestic violence", "physical violence", "sexual
      violence", "domestic violence", "postpartum depression", "postnatal depression",
      and "puerperal depression" were some of the terms included in the purview of MeSH
      terms. Relevant studies from reference lists were also scanned. Studies examining
      the association between violence and postpartum depression have been included. A
      total of 679 studies were included in this screening. Essential information of
      these included studies was independently extracted by two raters. Newcastle
      Ottawa scale was used to assess the clinical data of these research studies.
      Random-effects model was chosen in this meta-analysis for maintaining significant
      heterogeneity. Publication bias was evaluated with the help of a funnel plot. Six
      studies involving 3,950 participants were included in this clinical study.
      Violence was one of the factors responsible for PPD [OR = 3.47; 95% confidence
      interval (CI; 2.13-5.64)]. Significant heterogenity was found in this meta
      analysis (P < 0.00001; I (2) = 79%)and publication bias was detected through a
      funnel plot. A sensitivity analysis of 3.00, 95%CI (2.44-3.68), p < 0.00001
      indicated that our findings were robust and reliable. Our meta-analysis indicated
      a positive correlation between violence and PPD. In women of reproductive age,
      PPD induced through violence can be prevented through early identification. In
      addition, due to heterogeneity and wide CIs in this meta-analysis, further
      research is evidently required.

PMID- 22382279
TI  - Outcomes from implementing systematic antepartum depression screening in
      obstetrics.
AB  - This study was developed to evaluate the feasibility of implementing systematic
      depression screening in a large obstetric practice and to evaluate the degree
      that detection and referral led to linkage with behavioral healthcare. Depression
      screening was conducted using the Edinburgh Postnatal Depression Scale,
      administered at the initial pregnancy care appointment. Patients at or above a
      predetermined score of 14 were advised to seek further behavioral health
      assessment through the patient's behavioral healthcare coverage. Within 4 weeks
      of screening, those referred were contacted by telephone, by clinic staff, to
      determine whether they had pursued behavioral healthcare as recommended. Limited
      available data for newly established postdelivery screening were similarly
      evaluated. All 2,199 newly presenting pregnant women who were seen in our
      obstetric clinics from September 2008 to May 2009 were screened for depression,
      and 102 (4.6%) scored at or above an EPDS of 14. Follow-up calls revealed that
      none had pursued further behavioral health assessments. Of these 2,199, screening
      and follow-up data were available for 569 women at their 6-week postdelivery
      visit. Of these, 28 (4.9%) were above EPDS of 14, and 5 (17.9%) reported pursuit
      of further behavioral healthcare following screening and referral. Peripartum
      depression can be addressed with systematic screening, and the electronic medical
      record can readily be used to monitor results. Detection and referral at the
      beginning of pregnancy did not lead to intended linkage with behavioral
      healthcare, but detection and referral postdelivery had a modest influence.
      Barriers to pursuing behavioral healthcare need to be discovered and addressed.

PMID- 22382280
TI  - Suicidal ideation during pregnancy: prevalence and associated factors among low
      income women in Sao Paulo, Brazil.
AB  - The aim of this study was to estimate the prevalence and correlates of suicidal
      ideation among low-income pregnant women living in Brazil. We performed a cross
      sectional analysis of 831 women surveyed during 20 to 30 weeks of pregnancy using
      the Self-Report Questionnaire-20. The prevalence of suicidal ideation was 6.3%.
      The factors associated with suicidal ideation were common mental disorders,
      single partner status, past psychiatric history, and smoking tobacco. All cases
      of suicidal ideation were associated with common mental disorders.

PMID- 22382281
TI  - Mindful pregnancy and childbirth: effects of a mindfulness-based intervention on
      women's psychological distress and well-being in the perinatal period.
AB  - This pilot study explored the effects of an 8-week mindfulness-based cognitive
      therapy group on pregnant women. Participants reported a decline in measures of
      depression, stress and anxiety; with these improvements continuing into the
      postnatal period. Increases in mindfulness and self-compassion scores were also
      observed over time. Themes identified from interviews describing the experience
      of participants were: 'stop and think', 'prior experience or expectations',
      'embracing the present', 'acceptance' and 'shared experience'. Childbirth
      preparation classes might benefit from incorporating training in mindfulness.

PMID- 22382282
TI  - Infant gender and postpartum sadness in the light of region of birth and some
      other factors: a contribution to the knowledge of postpartum depression.
AB  - The purpose of this paper is to analyse postpartum depressive symptoms as related
      to baby gender, maternal region of birth, stress, perception of child difficult
      temperament and some demographic factors. The setting was 36 Swedish child health
      centres. Mothers of 1,848 19-month-old children completed a questionnaire,
      including an item about recall of postpartum sadness. A subsample of 360 answered
      the Edinburgh Postnatal Depression Scale (EPDS). Overall, significantly more
      mothers of boys than of girls recalled postpartum sadness. The same was found in
      mothers born in Sweden and in other regions, except for the Middle East (no
      significant result). Among those born in Sweden and in other regions, more
      mothers of boys than of girls scored >=12 on the EPDS, except for Middle East
      mothers with the opposite pattern (no significant finding). More mothers of
      "difficult" boys than of "difficult" girls recalled postpartum sadness. Our
      findings are tentative but may inspire future research. Immigrant mothers in
      Sweden seem rather like the majority population, possibly with the exception of
      Middle East mothers. The significance of parents' knowledge of their child's
      gender in advance is an important area for research. Future parents could benefit
      from discussing gender expectations with a nurse or other professional.

PMID- 22382283
TI  - Symptoms of depression during pregnancy are associated with increased systolic
      blood pressure responses towards infant distress.
AB  - A mother's response towards her infant's distress is important for the mother
      infant relationship and infant development. There is evidence that maternal
      responses are impaired in depressed mothers. Further understanding of how
      depression disrupts maternal responses is important to direct treatment
      strategies. There is evidence that maternal responses develop during pregnancy.
      Further understanding of the relationship between depression and maternal
      responses during pregnancy is therefore important. We have previously found that
      depression during pregnancy is associated with reduced attentional engagement
      with infant distress but is unclear whether this is an insensitive or avoidance
      response. In the current study, we investigated the impact of anhedonic symptoms
      of depression on pregnant women's autonomic response towards infant distress. We
      found that women experiencing anhedonic depressive symptoms during pregnancy had
      significantly larger systolic blood pressure responses towards infant distress
      (beta, 1.6 mmHg, 95 % CI 0.5 to 2.6, p = 0.004) than non-depressed pregnant
      women. These results suggest that anhedonic symptoms during pregnancy may be
      associated with increased sympathetic sensitivity. This suggests that depression
      is not, at a sympathetic level at least, associated with insensitivity to infant
      distress and rather depression may be associated with an abnormally sensitive
      response.

PMID- 22382284
TI  - Vitamin D in orthopaedics.
AB  - Vitamin D is an important component in musculoskeletal development, maintenance,
      and function. Adequate levels of vitamin D correlate with greater bone mineral
      density, lower rates of osteoporotic fractures, and improved neuromuscular
      function. Debate exists about both adequate levels required and intake
      requirements needed to prevent deficiency of vitamin D. Epidemiologic data have
      identified an increasing number of orthopaedic patients at risk for vitamin D
      deficiency, with potentially widespread consequences for bone healing, risk of
      fracture, and neuromuscular function.

PMID- 22382285
TI  - Management of scapular fractures.
AB  - With the exception of displaced articular glenoid fractures, management of
      scapular fractures has largely consisted of benign neglect, with an emphasis on
      motion as allowed by the patient's pain. Better understanding of this injury has
      resulted in greater acceptance of surgical management of highly displaced
      variants. However, little agreement exists on indications for surgery, and there
      is no clear comparative evidence on outcomes for surgically versus nonsurgically
      managed fractures. Scapular fractures are the result of high-energy mechanisms of
      injury, and they often occur in conjunction with other traumatic injuries. In
      addition to performing meticulous physical and neurologic examination, the
      surgeon should obtain plain radiographs, including AP shoulder, axillary, and
      scapular Y views. Three-dimensional CT is used to determine accurate measurements
      in surgical candidates. Surgical approach, technique, and timing are
      individualized based on fracture type and other patient-related factors.

PMID- 22382286
TI  - Induced membrane technique for reconstruction to manage bone loss.
AB  - Multiple surgeries are often required to manage segmental bone loss because of
      the complex mechanics and biology involved in reconstruction. These procedures
      can lead to prolonged recovery times, poor patient outcomes, and even delayed
      amputation. A two-stage technique uses induced biologic membranes with delayed
      placement of bone graft to manage this clinical challenge. In the first stage, a
      polymethyl methacrylate spacer is placed in the defect to produce a bioactive
      membrane, which appears to mature biochemically and physically 4 to 8 weeks after
      spacer placement. In the second, cancellous autograft is placed within this
      membrane and, via elution of several growth factors, the membrane appears to
      prevent graft resorption and promote revascularization and consolidation of new
      bone. Excellent clinical results have been reported, with successful
      reconstruction of segmental bone defects >20 cm.

PMID- 22382287
TI  - Radionuclide imaging in the diagnosis and management of orthopaedic disease.
AB  - Nuclear medicine imaging is often used in the diagnosis and management of several
      orthopaedic conditions. Bone scintigraphy measures gamma ray emission to detect
      the distribution of an injected radiolabeled tracer on multiple image
      projections. In general, this imaging modality has relatively high sensitivity
      but low specificity in the diagnosis of occult fractures, bone tumors, metabolic
      bone disease, and infection. Positron emission tomography measures tissue
      metabolism and perfusion by detecting short half-life positron ray emission of an
      injected radiopharmaceutical tracer. Historically, positron emission tomography
      has been used only to monitor bone metastasis and aid in the diagnosis of
      osteomyelitis; however, this technology has recently been applied to other
      orthopaedic conditions for which current imaging modalities are insufficient.

PMID- 22382288
TI  - The impact of the Spine Patient Outcomes Research Trial (SPORT) results on
      orthopaedic practice.
AB  - The benefits of spinal surgery for relief of low back and leg pain in patients
      with degenerative spinal disorders have long been debated. The Spine Patient
      Outcomes Research Trial (SPORT) was designed to address the need for high
      quality, prospectively collected data in support of such interventions. SPORT was
      intended to provide an evidential basis for spinal surgery in appropriate
      patients, as well as comparative and cost-effectiveness data. The trial studied
      the outcomes of the surgical and nonsurgical management of three conditions:
      intervertebral disk herniation, degenerative spondylolisthesis, and lumbar spinal
      stenosis. Both surgical and nonsurgical care of intervertebral disk herniation
      resulted in significant improvement in symptoms of low back and leg pain. Still,
      the treatment effect of surgery for intervertebral disk herniation was less than
      that seen in patients who underwent surgical versus nonsurgical treatment of
      degenerative spondylolisthesis and lumbar spinal stenosis. Across SPORT, more
      significant degrees of improvement with surgery were noted in chronic conditions
      of lumbar spinal stenosis and lumbar spinal stenosis with spondylolisthesis. In
      addition, no catastrophic progressions to neurologic deficit occurred as a result
      of watchful waiting.

PMID- 22382289
TI  - Stress fractures about the tibia, foot, and ankle.
AB  - In competitive athletes, stress fractures of the tibia, foot, and ankle are
      common and lead to considerable delay in return to play. Factors such as bone
      vascularity, training regimen, and equipment can increase the risk of stress
      fracture. Management is based on the fracture site. In some athletes, metabolic
      workup and medication are warranted. High-risk fractures, including those of the
      anterior tibial diaphysis, navicular, proximal fifth metatarsal, and medial
      malleolus, present management challenges and may require surgery, especially in
      high-level athletes who need to return to play quickly. Noninvasive treatment
      modalities such as pulsed ultrasound and extracorporeal shock wave therapy may
      have some benefit but require additional research.

PMID- 22382290
TI  - Sprengel deformity: pathogenesis and management.
AB  - Sprengel deformity (ie, congenital elevation of the scapula) is a rare clinical
      entity. However, it is the most common congenital anomaly of the shoulder.
      Sprengel deformity is caused by abnormal descent of the scapula during embryonic
      development. Sprengel deformity is associated with cosmetic deformity and
      decreased shoulder function. Diagnostic confusion with limited scoliosis can be
      dangerous to the patient because it may delay proper treatment of other
      abnormalities that may be present with even mild cases. Sprengel deformity is
      commonly linked to a variety of conditions, including Klippel-Feil syndrome,
      scoliosis, and rib anomalies. Nonsurgical management can be considered for mild
      cases. Surgical management is typically warranted for more severe cases, with the
      goal of improving cosmesis and function. Surgical techniques are centered on
      resection of the protruding portion of the scapula and inferior translation of
      the scapula. Recent long-term studies indicate that patients treated surgically
      maintain improved shoulder function and appearance.

PMID- 22382291
TI  - Fate of selected estrogens in two laboratory scale sequencing batch reactors fed
      with different organic carbon sources under varying solids retention times.
AB  - This study compared the performances of two laboratory-scale sequencing batch
      reactors to remove 17beta-estradiol and 17alpha-ethinyl estradiol. Both SBRs were
      operated to achieve organic carbon oxidation and nitrification. However, the
      overall bacterial population in both SBRs was targeted to be different by feeding
      the SBRs with peptone and glucose. Furthermore, the reactors were also run at
      different solid retention times (SRTs) to evaluate the effect of SRT on estrogen
      removal. The more diverse heterotrophic and ammonia oxidizing bacterial community
      in the peptone fed SBR1 had superior estrogen removal than the glucose fed SBR 2
      which enriched less diverse community, particularly for 17alpha-ethinyl
      estradiol. Under a solids retention time (SRT) of 40days, the total 17beta
      estradiol mass was 30% of the amount under the SRT of 20days, and the total
      17alpha-ethinyl estradiol mass was likewise 40% of the amount under the shorter
      SRT.

PMID- 22382292
TI  - Enhanced phenol degradation in coking wastewater by immobilized laccase on
      magnetic mesoporous silica nanoparticles in a magnetically stabilized fluidized
      bed.
AB  - The immobilized laccase on magnetic mesoporous silica nanoparticles has been
      developed for efficient phenol degradation. The degradation rate of phenol by the
      immobilized laccase was 2-fold higher than that of the free laccase, and the
      immobilized laccase retained 71.3% of its initial degradation ability after 10
      successive batch treatments of coking wastewater. The phenol degradation in the
      coking wastewater was enhanced in a continuous treatment process by the
      immobilized laccase in a magnetically stabilized fluidized bed (MSFB) because of
      good mixing and mass transfer. The degradation rate of phenol maintained more
      than 99% at a flow rate of less than 450mLh(-1) and decreased slowly to 91.5%
      after 40h of the continuous operation in the MSFB. The present work indicated
      that the immobilized laccase on magnetic mesoporous supports together with the
      MSFB provided a promising avenue for the continuous enzymatic degradation of
      phenolic compounds in industrial wastewater.

PMID- 22382293
TI  - Recovery of silver from silver(I)-containing solutions in bioelectrochemical
      reactors.
AB  - A novel approach was tested for metallic silver recovery and power generation by
      using cathodic reduction in bioelectrochemical systems (BESs). In dual-chamber
      BESs (130 mL volume) with acetate as electron donor on anode, both Ag(+) ions and
      Ag(I) thiosulfate complex in catholyte were reduced on cathode. The reduction
      rate of Ag(+) was more rapid than the Ag(I) complex as expected by energetic
      analysis. X-ray diffraction (XRD) analysis indicated that electrodeposits on
      cathodes from both catholyte were metallic silver with >91% purity. The
      feasibility of metallic silver recovery with the BESs was confirmed using
      simulated photographic wastewater and up to 95% of Ag(I) removal was achieved.

PMID- 22382294
TI  - Effect of cultivation parameters on the production of poly(3-hydroxybutyrate-co-4
      hydroxybutyrate) and poly(3-hydroxybutyrate-4-hydroxybutyrate-3-hydroxyvalerate)
      by Cupriavidus necator using waste glycerol.
AB  - Short-chain polyhydroxyalkanoate co-polymers (poly(3-hydroxybutyrate-co-4
      hydroxybutyrate)) (P(3HB-co-4HB)) and terpolymers (poly(3-hydroxybutyrate-4
      hydroxybutyrate-3-hydroxyvalerate)) (P(3HB-4HB-3HV)) were produced using high
      cell density fed-batch cultures of Cupriavidus necator DSM 545. C-source for
      growth and 3HB synthesis was waste glycerol (GRP) from a biodiesel plant.
      Incorporation of 4HB monomers was promoted by gamma-butyrolactone (GBL).
      Propionic acid (PA), a stimulator of 4HB accumulation, increased the 4HB molar
      ratio 2-fold, but also acted as 3HV precursor, yielding P(3HB-4HB-3HV). Dissolved
      oxygen (DOC) was a key parameter for % PHA accumulation and volumetric
      productivity (Prod(vol)). 4HB molar ratio increased in the presence of PA and
      with extended accumulation time. By manipulating DOC and cultivation time, P(3HB
      4HB) with between 11.4 and 21.5 molar% of 4HB were attained. Similarly, P(3HB-4HB
      3HV) was obtained with 4HB molar% between 24.8% and 43.6% and 3HV% from 5.6% to
      9.8%. Mw varied between 5.5 * 10(5) and 1.37 * 10(6)Da. PHA production from GRP
      helps reducing production costs with concomitant GRP valorization.

PMID- 22382295
TI  - The influence of recycling non-condensable gases in the fractional catalytic
      pyrolysis of biomass.
AB  - In this study, the effect of recycling the non-condensable gases (NCG) in the
      catalytic pyrolysis of hybrid poplar using FCC catalyst was investigated. A 50mm
      bench scale fluidized bed reactor at 475 degrees C with a weight hourly space
      velocity (WHSV) of 2h(-1) and a gas recycling capability was used for the
      studies. Model fluidizing gas mixtures of CO/N(2), CO(2)/N(2), CO/CO(2)/N(2) and
      H(2)/N(2) were used to determine their independent effects. Recycling of the NCG
      in the process was found to potentially increase the liquid yield and decrease
      char/coke yield. The model fluidizing gases increased the liquid yield and the
      CO(2)/N(2) fluidizing gas had the lowest char/coke yield. The (13)C-NMR analysis
      showed that recycling of NCG increases the aromatic fractions and decreases the
      methoxy, carboxylic and sugar fractions. Recycling of NCG increased the higher
      heating value and the pH of the bio-oil as well as decreased the viscosity and
      density.

PMID- 22382296
TI  - Immersed membrane bioreactors: an overview with special emphasis on anaerobic
      bioprocesses.
AB  - Immersed membrane bioreactor (IMBR) has emerged as a novel potential technology
      which is considered globally as potent technology, primarily for wastewater
      treatment. It offers quality improvement in effluents treatment compared to other
      technological systems. It also offers potential benefits for the bioprocesses
      where product formation and separation is desired simultaneously in a compact
      container. This review gives insight for the wide range applications of IMBR
      focussing on anaerobiosis. It discusses the significance, advantages and
      drawbacks of IMBR against the conventional methods, highlighting the external
      membrane bioreactors. While the commercial significance of IMBR is obvious for
      industrial and municipal wastewater treatment, the current focus is shifting on
      other applications such as anaerobic bioprocesses. Though the IMBR technology is
      generally considered hand-in-hand as sustainable technology, the major bottleneck
      in its application at commercial scale for wastewater treatment seems its
      economic feasibility and compatibility. Among the technical issues, the membrane
      fouling is considered as a major problem for which several strategies have been
      developed to overcome the problem, though there is no complete or universal
      solution to this problem.

PMID- 22382297
TI  - A biofilter integrated with gas membrane separation unit for the treatment of
      fluctuating styrene loads.
AB  - Biofiltration for volatile organic compound control in waste gas streams is best
      operated at steady contaminant loadings. To provide long-term stable operation of
      a biofilter under adverse contaminant feeding conditions, an integrated
      bioreactor system with a gas separation membrane module installed after a
      biofilter was proposed for styrene treatment. Styrene was treated effectively,
      with average styrene effluent concentrations maintained at less than 50 mg m(-3)
      and a total removal efficiency of over 96% achieved when the biofiltration column
      faced fluctuating loads. The maximum elimination capacity of the integrated
      bioreactor system was 93.8 g m(-3)h(-1), which was higher than that obtained with
      the biofiltration column alone. The combination of these two processes (microbial
      and chemical) led to more efficient elimination of styrene and buffering of the
      fluctuating loads. The factors on gas membrane separation, microbial
      characteristics in the integrated bioreactor and membrane fouling were also
      investigated in this study.

PMID- 22382298
TI  - Degradation of phenolics, nitrogen-heterocyclics and polynuclear aromatic
      hydrocarbons in a rotating biological contactor.
AB  - The degradation of phenolics, heterocyclics and polynuclear aromatic hydrocarbons
      (PAHs) in a synthetic biomass gasifier wastewater with average COD of 1388 mg/L
      was studied in a three stage rotating biological contactor (RBC) using the pyrene
      degrader, Exiguobacterium aurantiacum and activated sludge consortia (1:3 v/v).
      As the organic loading rate (OLR) was varied from 3.3 to 14 g/m(2)/d, the COD
      removal ranged from 63.3% to 92.6%. Complete removal of all the constituents was
      observed at the lowest OLR of 3.3g/m(2)/d. At 24h hydraulic retention time (HRT)
      and OLR of 6.6g/m(2)/d complete removal of pyridine, quinoline and benzene and 85
      96% removal of phenol, naphthalene, phenanthrene, fluoranthene and pyrene was
      observed. E. aurantiacum was found to be the dominant bacteria in the biofilm.
      Clark's model provided good fits to data for all the three stages of the RBC.

PMID- 22382299
TI  - Live monitoring of small vessels during development and disease using the flt-1
      promoter element.
AB  - Vessel formation is of critical importance for organ function in the normal and
      diseased state. In particular, the labeling and quantitation of small vessels
      prove to be technically challenging using current approaches. We have, therefore,
      established a transgenic embryonic stem (ES) cell line and a transgenic mouse
      model where the vascular endothelial growth factor receptor VEGFR-1 (flt-1)
      promoter drives the expression of the live reporter eGFP. Fluorescence microscopy
      and immunostainings revealed endothelial-specific eGFP labeling of vascular
      networks. The expression pattern recapitulates that of the endogenous flt-1 gene,
      because small and large vessels are labeled by eGFP during embryonic development;
      after birth, the expression becomes more restricted to small vessels. We have
      explored this in the cardiovascular system more in detail and found that all
      small vessels and capillaries within the heart are strongly eGFP+. In addition,
      myocardial injuries have been induced in transgenic mice and prominent vascular
      remodeling, and an increase in endothelial cell area within the peri-infarct area
      could be observed underscoring the utility of this mouse model. Thus, the
      transgenic flt-1/eGFP models are powerful tools to investigate and quantify
      vascularization in vivo and to probe the effect of different compounds on vessel
      formation in vitro.

PMID- 22382300
TI  - Species and phylogenetic nomenclature.

PMID- 22382301
TI  - Response to: letter to the editor.

PMID- 22382302
TI  - A mitochondria-localized two-photon fluorescent probe for ratiometric imaging of
      hydrogen peroxide in live tissue.
AB  - We report a two-photon fluorescent probe (SHP-Mito) which can ratiometrically
      detect mitochondrial H(2)O(2) in live cells and intact tissues at >100 MUm depth
      through the use of two-photon microscopy.

PMID- 22382303
TI  - [Nail psoriasis--an ignored disorder. Pathogenesis, diagnosis and therapy].
AB  - Approximately 50% of all patients with psoriasis develop characteristic nail
      changes as a clinical correlate of psoriatic inflammation of the nail matrix
      and/or nail bed. The most frequent signs of nail psoriasis are pitting and distal
      onycholysis. The most commonly used score to assess the severity of nail
      involvement at present is the Nail Psoriasis Severity Index (NAPSI). Although
      more than half of affected patients experience a significant physical and mental
      impairment, this index does not include patient-reported symptoms. There is a
      striking association between nail psoriasis and a higher risk of psoriatic
      arthritis with a prevalence of nail involvement among patients with psoriatic
      arthritis as high as 70%. A possible explanation is the close anatomical link
      between the nail apparatus and the distal interphalangeal joint; enthesitis of
      the latter is carried by fibers to the nail and becomes clinically visible as
      nail psoriasis. Nail involvement is not adequately reflected in current concepts
      of disease management. There is limited evidence for the efficacy of topical
      therapies in nail psoriasis. A number of large studies document an improvement of
      nail psoriasis in response to biologics and, more recently, also to methotrexate.

PMID- 22382304
TI  - [Children and adolescents with psoriasis. What therapy is recommended?].
AB  - Juvenile psoriasis shows a cumulative incidence of 1.76% until the 18th year of
      life and thus is important for both pediatricians and dermatologists. In contrast
      to psoriasis in adults, the main trigger factors are infections, mechanical
      trauma and stress factors and to a much lesser extent medical and recreational
      drugs. Apart from the classical predilection sites, the diaper area, scalp and
      face are mainly involved. Guttate psoriasis following streptococcal infections is
      a specific clinical manifestation in childhood and adolescence. Psoriasis
      arthritis of childhood falls into the group of juvenile idiopathic arthritis and
      typically presents before or simultaneously with skin symptoms. All recommended
      childhood vaccinations should be administered, ideally when the disease is under
      remission. Therapy relies heavily on topical agents like dithranol,
      corticosteroids, and alternatively topical calcineurin inhibitors in addition to
      individually adapted skin moisturizing measures. In severe cases which do not
      adequately respond to topical therapy, systemic treatment with classical
      immunomodulatory agents like methotrexate, cyclosporin, retinoids and fumarates
      may be initiated but all usage is off-label. The only agent licensed for the
      treatment of psoriasis in patients above the age of 8 years is etanercept if
      classical treatment has failed. Rehabilitative measures in mountain and seaside
      areas are reasonable for maintaining improvement and helping patient learn to
      deal with disease.

PMID- 22382305
TI  - [Belimumab. A new targeted therapeutic option for lupus erythematosus].

PMID- 22382306
TI  - [Disseminated infiltrated cutaneous pruritis].
AB  - The diagnosis of scabies is clinically not always simple without the detection of
      mites. Histology can be difficult, particularly without clinico-pathologic
      correlation. [corrected] Even after adequate antiscabies treatment the
      dermatological symptoms and complaints can persist and necessitate an [corrected]
      intensive follow-up treatment. The case example described here underlines that in
      consideration of the multifaceted clinical appearance and the sometimes difficult
      detection of mites, scabies should always be considered as a differential
      diagnosis in cases of persistent pruritis.

PMID- 22382307
TI  - Investigating the copper coordination, electrochemistry, and Cu(II) reduction
      kinetics of biologically relevant selone and thione compounds.
AB  - Selenium- and sulfur-containing compounds can act as antioxidants by binding
      copper. To determine how this copper coordination results in the observed
      antioxidant activity, biologically relevant Cu(+) and Cu(2+) complexes with the
      formulae [Cu(dmit)(3)](+) (3), [Cu(dmise)(4)](+) (4a), and
      [Tpm(iPr)Cu(MISeox)](2+) (6) (dmise = N,N'-dimethylimidazole selone; dmit = N,N'
      dimethylimidazole thione; MISeox = bis(1-methylimidazolyl)diselenide; Tpm(iPr) =
      tris(1,3-diisopropylpyrazolyl)methane) were synthesized, characterized, and their
      structures determined by single-crystal X-ray crystallography. In addition,
      kinetic studies using UV-vis spectroscopy indicate that dmise reduces Cu(2+) to
      Cu(+) three times faster than dmit. Coordination of dmise and MISeox to copper
      also results in more negative Cu(2+/+) reduction potentials (-373 mV and -503 mV)
      compared to dmit (-217 mV). These results highlight the different complexation
      behaviors and reactivities of analogous selone- and thione-containing compounds,
      traits which likely influence their antioxidant activity.

PMID- 22382308
TI  - Improved imaging of intrahepatic colorectal metastases with 18F
      fluorodeoxyglucose respiratory-gated positron emission tomography.
AB  - BACKGROUND: In 18F-fluorodeoxyglucose PET/CT, respiratory motion induces bias in
      image interpretations (i.e. organ misregistration or lesion
      omission/underestimation). OBJECTIVE: The present study applied our custom gating
      method (referred to as 'CT-based gated PET' and that has already been validated
      by our research group) to PET imaging of the liver and compared its per lesion
      sensitivity with that of standard clinical (i.e. ungated) PET. METHODS: A total
      of 13 patients scheduled for liver surgery were referred to our department for
      PET/CT imaging. Each patient underwent both ungated and CT-based gated PET
      imaging protocols. Two independent, blinded observers interpreted the two sets of
      PET images and reached a consensus when necessary. Image interpretations were
      combined with histological analysis and/or intraoperative ultrasound examination
      to compute each method's per lesion sensitivity and true positive fraction.
      Analyses were also performed by considering lesions according to their size
      (longest axis over 10 mm or over 15 mm). RESULTS: Forty-eight lesions were
      confirmed by pathology reports. When considering all the uptakes, the ungated and
      the CT-based gated PET methods had sensitivities of 54.2 and 64.6% (P=0.025) and
      true positive fractions of 83.9 and 86.1%, respectively. When considering uptakes
      greater than 10 mm in size, ungated and CT-based gated PET had sensitivities of
      74.3 and 88.6% (P=0.025), respectively. For lesions greater than 15 mm in size,
      the corresponding sensitivities were 85.2 and 100% (P=0.046). CONCLUSION: CT
      based gated PET yielded a higher lesion-based sensitivity than routine, ungated
      PET did. Hence, this method improves the detection of intrahepatic colorectal
      metastases--especially for lesions that are close in size to the detection limit
      of the PET gantry.

PMID- 22382309
TI  - The prevalence of CD33 and MS4A6A variant in Chinese Han population with
      Alzheimer's disease.
AB  - CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's
      disease (AD). One recent genome-wide association study has revealed that the
      rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A
      gene are associated with susceptibility to AD in Caucasians. To evaluate the
      relationship between the polymorphism of the CD33, MS4A6A gene and AD in the
      ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to
      determine the prevalence of single-nucleotide polymorphism of two genes in
      patients with AD in Chinese population of Mainland, and clarified whether these
      polymorphisms are risk factors for AD. The prevalence of the allele (T) in the
      rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism
      of the MS4A6A gene was significantly different in AD patients and control
      subjects (P < 0.001, respectively), and the results were not influenced by age,
      gender, or APOE status. Our data revealed the allele (T) of the rs3865444
      polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of
      the MS4A6A gene may contribute to AD risk in the Chinese Han population.

PMID- 22382310
TI  - DNA repair gene deficiency does not predispose human bronchial epithelial cells
      to benzo(a)pyrene-induced cell transformation.
AB  - The development of cost and time-efficient in vitro assays to predict
      carcinogenicity of chemicals has become a very important direction for
      toxicological research. In this study, we generated a series of human bronchial
      epithelial (HBE) cells defect in DNA repair gene excision repair cross-completion
      1 (ERCC1), excision repair cross-completion 2 (ERCC2), ataxia-telangiectasia
      mutated (ATM) and mutS homolog 2 (MSH2), respectively. The inhibition of gene
      expression was verified by detection of mRNA and protein levels of respective
      genes. The suppression of these DNA repair genes has no impact on cell
      proliferation or cell transformation. Although we found that the transgenic HBE
      cells were more sensitive in benzo(a)pyrene (BaP)-induced DNA damages measured by
      cytokinesis-block micronucleus (CBMN) assay and comet assay, we failed to observe
      enhanced effects on induction of cell transformation. HBE cells defect in DNA
      repair pathways did not exhibit malignantly transformed phenotype up to 20 weeks
      of BaP treatment, indicating that the deficiency of ERCC1, ERCC2, ATM, or MSH2
      alone did not shorten the latency of cell transformation. In contrast, we found
      that HBE cells expressing H-Ras or c-Myc were transformed 8 or 12 weeks after BaP
      treatment. These findings demonstrate that silencing of a single DNA repair gene
      does not confer cells susceptible to chemical-induced cell transformation.

PMID- 22382311
TI  - Recent advances in the study on resveratrol.
AB  - Appropriate long-term drinking of red wine is associated with a reduced risk for
      lifestyle-related diseases such as cardiovascular disease and cancer, making
      resveratrol, a constituent of grapes and various other plants, an attractive
      compound to be studied. Historically, resveratrol has been identified as a
      phytoalexin, antioxidant, cyclooxygenase (COX) inhibitor, peroxisome proliferator
      activated receptor (PPAR) activator, endothelial nitric oxide synthase (eNOS)
      inducer, silent mating type information regulation 2 homolog 1 (SIRT1) activator,
      and more. Despite scepticism concerning the biological availability of
      resveratrol, a growing body of in vivo evidence indicates that resveratrol has
      protective effects in several stress and disease models. Here, we provide a
      review of the studies on resveratrol, especially with respect to COX, PPAR, and
      eNOS activities, and discuss its potential for promoting human health.

PMID- 22382312
TI  - Site-specific chemical modification of human serum albumin with polyethylene
      glycol prolongs half-life and improves intravascular retention in mice.
AB  - Human serum albumin (HSA) is used as an important plasma volume expander in
      clinical practice. However, the infused HSA may extravasate into the interstitial
      space and induce peripheral edema in treating the critical illness related to
      marked increase in capillary permeability. Such poor intravascular retention also
      demands a frequent administration of HSA. We hypothesize that increasing the
      molecular weight of HSA by PEGylation may be a potential approach to decrease
      capillary permeability of HSA. In the present study, HSA was PEGylated in a site
      specific manner and the PEGylated HSA carrying one chain of polyethylene glycol
      (PEG) (20 kDa) per HSA molecule was obtained. The purity, PEGylated site and
      secondary structure of the modified protein were characterized by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE), thiol group blockage
      method and circular dichroism (CD) measurement, respectively. In addition, the
      pharmacokinetics in normal mice was investigated, vascular permeability of the
      PEGylated HSA was evaluated in lipopolysaccharide (LPS)-induced lung injury mouse
      model and the pharmacodynamics was investigated in LPS-induced sepsis model with
      systemic capillary leakage. The results showed that the biological half-life of
      the modified HSA was approximately 2.3 times of that of the native HSA, PEG-HSA
      had a lower vascular permeability and better recovery in blood pressure and
      haemodilution was observed in rats treated with PEG-HSA. From the results it can
      be inferred that the chemically well-defined and molecularly homogeneous
      PEGylated HSA is superior to HSA in treating capillary permeability increase
      related illness because of its longer biological half-life and lower vascular
      permeability.

PMID- 22382313
TI  - Kalopanaxsaponin A inhibits the invasion of human oral squamous cell carcinoma by
      reducing metalloproteinase-9 mRNA stability and protein trafficking.
AB  - An inability to control cancer cell invasion and metastasis is the leading cause
      of death in patients with cancer. The present study was performed to determine
      the anti-invasive effect of Kalopanaxsaponin A (KPS-A) on matrix
      metalloproteinase-9 (MMP-9)-meidated invasion in phorbol 12-myristate 13-acetate
      (PMA)-stimulated human oral squamous cell carcinoma (OSCC) cells and a murine
      xenograft model of human OSCC. KPS-A, isolated from Kalopanax pictus, inhibited
      PMA-induced proliferation and invasion as well as PMA-induced MMP-9 expression
      and secretion at non-cytotoxic doses. KPS-A treatment reduced the stability of
      PMA-induced MMP-9 mRNA and inhibited the PMA-induced cytoplasmic translocation of
      HuR. In PMA-treated cells, KPS-A treatment resulted in the intracellular
      accumulation of MMP-9 and suppressed Ras-associated binding 1A (Rab1A)
      expression. KPS-A treatment suppressed PMA-induced phosphorylation of
      extracellular signal regulated kinase (ERK)1/2 and Akt. Furthermore, the oral
      administration of KPS-A led to substantial inhibition of tumor growth and the
      expression of proliferating cell nuclear antigen (PCNA), MMP-9, tissue inhibitor
      of metalloproteinase-1 (TIMP-1), HuR, and Rab1A in the tumor tissues of mice
      inoculated with YD-10B OSCC cells. Collectively, KPS-A inhibits the invasiveness
      of oral cancer by reducing HuR-mediated MMP-9 mRNA stability and Rab1A-mediated
      MMP-9 secretion via ERK1/2 and phosphatidylinositide 3-kinase (PI3K)/Akt.
      Therefore, KPS-A is a promising anti-invasive agent.

PMID- 22382314
TI  - Different involvement of DNA methylation and histone deacetylation in the
      expression of solute-carrier transporters in 4 colon cancer cell lines.
AB  - The purpose of this study on the involvement of epigenetic control of the
      expression of solute carrier (SLC) transporters by DNA methylation and histone
      deacetylation in 4 colon cancer cells is to find the epigenetic control
      mechanisms of drug transporters in colon cancers. Human colon cancer cell lines
      (HCT116, HT29, SW48, SW480) were treated with 5-aza-2'-deoxycytidine (DAC), as a
      DNA methyltransferase inhibitor, followed by trichostatin A (TSA), as a histone
      deacetylase inhibitor. The mRNA expression and DNA methylation of several SLC
      transporters were analyzed by real-time polymerase chain reaction (PCR) and
      methylation-specific PCR, respectively. Among 12 SLC transporters possessing
      cytosine-phosphate-guanine (CpG) islands, thiamine transporter 2 (THTR2)
      (SLC19A3) gene showed a correlation between its mRNA expression level and DNA
      methylation status. TSA treatment increased histone H3 acetylation of THTR2
      promoter region in all 4 colon cancer cell lines examined. HCT116 and SW48 cells
      showed a lack of THTR2 mRNA expression and methylation of its promoter, and DAC
      treatment induced its re-expression. In addition, the co-treatment with DAC and
      TSA increased THTR2 mRNA expression more markedly than DAC treatment in HCT116
      and SW48 cells. In HT29 and SW480 cells that showed little methylation of THTR2
      promoter, TSA treatment induced THTR2 mRNA expression markedly, but DAC treatment
      did not. In the 4 colon cancer cells examined, THTR2 mRNA expression is down
      regulated by DNA methylation and/or histone deacetylation.

PMID- 22382315
TI  - Stirred suspension culture improves embryoid body formation and cardiogenic
      differentiation of genetically modified embryonic stem cells.
AB  - Embryonic stem cells (ESCs) can propagate unlimitedly in vitro and differentiate
      into cardiomyocytes, which have been proposed as unlimited cell sources for
      cardiac cell therapy. This was limited by difficulties in large-scale generation
      of pure cardiomyocytes. In this study, we used stirred bioreactors to optimize
      the differentiation condition for mass production of embryoid bodies (EBs)
      derived from genetically modified mouse ESCs. Stirred suspension culture could
      more efficiently produce EBs and have a more uniform EB population without large
      necrotic centers, compared with the conventional static culture. Importantly, the
      cardiac-specific gene expressions (GATA binding protein 4, alpha-cardiac myosin
      heavy chain and myosin light chain-2v) were increased within EBs cultured in
      stirred bioreactor. Stirred suspension culture significantly increased the
      proportion of spontaneously contracting EBs, yielded a greater percentage of
      alpha-sarcomeric actinin-positive cells detected via flow cytometry, and
      harvested relatively more cardiomyocytes after G418 selection. Stirred suspension
      culture provided a more ideal culture condition facilitating the growth of EBs
      and enhancing the cardiogenic differentiation of genetically modified ESCs, which
      may be valuable in large-scale generation of pure cardiomyocytes.

PMID- 22382316
TI  - Influence of cytochrome P450 2C19 gene variations on pharmacokinetic parameters
      of thalidomide in Japanese patients.
AB  - PURPOSE: Cytochrome P450 (CYP)2C19 polymorphisms may partly explain the
      variability of thalidomide concentration and adverse drug effects by altering its
      metabolism. To compare the genetic and clinical factors responsible for the
      adverse effects and efficacy of thalidomide treatment, we investigated CYP2C19
      genetic polymorphisms in Japanese subjects. MATERIALS AND METHODS: Variations in
      the CYP2C19 gene in 6 patients treated with thalidomide were analyzed. The dosage
      of thalidomide, concentrations of (R)- and (S)-thalidomide in whole blood, and
      clinical laboratory test results were used as pharmacokinetic and pharmacodynamic
      indices. Using genomic DNA, CYP2C19*2 and *3 allele frequencies were determined
      by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assays. RESULTS: The frequencies of CYP2C19 PM and hetero EM (hetEM) genotypes in
      Japanese patients taking thalidomide were 2 (33.3%) and 4 (66.7%), respectively.
      The areas under the curve (AUC) of (R)-thalidomide were 3.42 and 5.33 MUg.h/L,
      and those of (S)-thalidomide were 1.64 and 2.46 MUg.h/L for hetEM and PM,
      respectively. CONCLUSIONS: This study provided new insights regarding the
      contribution of CYP2C19 gene variations to adverse responses to thalidomide.
      Genotyping of CYP2C19*2 and *3 can be considerably simplified by using KOD FX as
      a polymerase for prediction of adverse effects to thalidomide by the PCR-RFLP
      method. CYP2C19 PM patients tend to have high serum thalidomide concentrations.

PMID- 22382317
TI  - Development of transdermal therapeutic formulation of CNS5161, a novel N-methyl-D
      aspartate receptor antagonist, by utilizing pressure-sensitive adhesives I.
AB  - The aim of this study was to investigate the feasibility of percutaneous
      absorption of CNS5161, a novel N-methyl-D-aspartate (NMDA) receptor antagonist
      developed as a potential treatment for neuropathic pain and other neurological
      disorders. Six pressure-sensitive adhesives (PSA) with different physicochemical
      properties, namely, styrene-isoprene-styrene (1) (SIS(1)), styrene-isoprene
      styrene (2) (SIS(2)), silicone, acrylate with a hydroxyl group (acrylate(OH)),
      acrylate without a functional group (acrylate(none)) and acrylate with a carboxyl
      group (acrylate(COOH)), were investigated for their release of CNS5161 and its
      subsequent skin permeability. Among the adhesives examined, silicone PSA provided
      the highest value of transdermal flux of CNS5161, which could be attributable to
      the highest release rate from it due to its very high thermodynamic activity.
      Although CNS5161 was also in the supersaturated state in SIS(1) and SIS(2) PSAs,
      the release and transdermal permeation from these adhesives were slower than
      those from silicone PSA. As for the acrylic PSAs, the highest release rate and
      permeability of CNS5161 were observed for acrylate(OH) PSA, followed by
      acrylate(none) and acrylate(COOH) PSAs, but none of them was better in terms of
      either the release or the permeability of CNS5161 than silicone PSA. These
      results clearly indicated that silicone PSA would be the most suitable for
      transdermal delivery of CNS5161 and silicone PSA containing 10% CNS5161 would be
      suitable for clinical use in humans.

PMID- 22382318
TI  - Mechanism-based inhibition of recombinant human cytochrome P450 3A4 by tomato
      juice extract.
AB  - This study investigates whether tomato juice can inhibit cytochrome P450 (CYP)
      3A4-mediated drug metabolism. Three commercially available, additive-free tomato
      juices, along with homogenized fresh tomato, were analyzed for their ability to
      inhibit testosterone 6beta-hydroxylation activity using human recombinant CYP3A4.
      Results were compared to that of grapefruit juice. Ethyl acetate extracts of the
      tomato juices moderately reduced residual activity of CYP3A4 testosterone 6beta
      hydroxylation activity by 19.3-26.2% with 0-min preincubation. Residual activity
      was strongly reduced by 69.9-83.5% at 20-min preincubation, a reduction similar
      to that of grapefruit juice extract, known to contain constituents of mechanism
      based inhibitors. One juice extract (tomato juice C) showed irreversible dose-
      and preincubation time-dependent and partial nicotinamide adenine dinucleotide
      phosphate (NADPH)-dependent inhibition of CYP3A4 activity. Furthermore, we
      examined whether the CYP3A4 inhibitory effect of tomato juice was substrate
      dependent by examining midazolam 1'-hydroxylation activity and nifedipine
      oxidation activity, in addition to testosterone 6beta-hydroxylation activity.
      Tomato juice showed a potent inhibitory effect on nifedipine oxidation activity,
      which was comparable to that on testosterone 6beta-hydroxylation activity;
      however, it showed a weak inhibitory effect on midazolam 1'-hydroxylation
      activity. We conclude that tomato juice contains one or more mechanism-based and
      competitive inhibitor(s) of CYP3A4. Additionally, significant CYP3A4 inhibitory
      activity did not result from lycopene, a major compound in tomato. Although the
      active compound was uncertain, a strong CYP3A4 inhibitory activity was observed
      in other solanaceous plants, i.e., potato, eggplant, sweet pepper, and capsicum.
      Therefore, responsible compounds in tomato are likely commonly shared among
      solanaceous vegetables.

PMID- 22382319
TI  - A novel and facile approach to imaging nanoparticles transport across Transwell
      filter grown cell monolayer in real-time and in situ under confocal laser
      scanning microscopy.
AB  - Although the cellular endocytosis or uptake research using confocal laser
      scanning microscopy (CLSM) and Transwell inserts was frequently reported in
      experimental cell research and pharmaceutical research, there is little report on
      cellular transport process based on the same techniques. One of main reasons is
      that fluorescence of most fluorescent reagents could be clearly and definitely
      seen under CLSM only when they are internalized into and concentrated within
      cells. Here, Madin-Darby Canine Kidney (MDCK) cells and Coumarin 6 labeled
      nanoparticles (C6-NPs) was used as models, a new system was developed to image C6
      NPs transport across Transwell filter grown cell monolayer by adding free cells
      into the basolateral medium and making the Transwell insert semi-permeable
      membrane visible under CLSM. The transport process could be clearly imaged in
      real-time and in situ, based on the visualization of Transwell membrane
      indicating the relative position of cells and nanoparticles, and the free cells
      in the basolateral medium serving as collector and indicator for the transported
      nanoparticles. The method was also applied in cell migration study. We believe
      that the novel approach developed here will be certainly useful not only in
      exploration of nanoparticle cellular transport mechanism, but also in other cell
      biological sciences based on CLSM and Transwell.

PMID- 22382320
TI  - Possible involvement of transient receptor potential channels in electrophile
      induced insulin secretion from RINm5F cells.
AB  - Endogenously produced reactive oxygen species reportedly stimulate insulin
      secretion from islet beta-cells. However, the molecular machinery that governs
      the oxidant-induced insulin secretion has yet to be determined. The present study
      demonstrates, using rat islet beta-cell-derived RINm5F cells, the involvement of
      the transient receptor potential (TRP) cation channels in the insulin secretion
      induced by the lipid peroxidation product 4-hydroxy-2-nonenal. Short-term (1 h)
      exposure of 4-hydroxy-2-nonenal induced a transient increase in intracellular
      Ca(2+) concentration and subsequent insulin secretion in a concentration
      dependent manner. The increase in intracellular Ca(2+) concentration seemed to be
      due to an influx through the L-type voltage-dependent Ca(2+) channel, since it
      was not observed when extracellular Ca(2+) was absent and was inhibited almost
      completely by diltiazem or nifedipine. Ruthenium red, a non-specific inhibitor of
      TRP channels, inhibited the Ca(2+) influx and insulin secretion evoked by 4
      hydroxy-2-nonenal. Among the TRP channels, TRPA1 was found to be predominantly
      expressed, not only in RINm5F cells, but also rat islets. TRPA1 agonists,
      allylisothiocyanate and 15-deoxy-Delta(12,14)-prostaglandin J(2), significantly
      induced Ca(2+) influx, and a specific inhibitor TRPA1, HC-030031, blocked the
      effects elicited by 4-hydroxy-2-nonenal. These results suggest that 4-hydroxy-2
      nonenal induces Ca(2+) influx via the activation of TRP channels, including
      TRPA1, which appears to be coupled with the L-type voltage-dependent Ca(2+)
      channel, and ultimately insulin secretion in RINm5F cells.

PMID- 22382321
TI  - Huanglian-Jie-Du-Tang extract protects against chronic brain injury after focal
      cerebral ischemia via hypoxia-inducible-factor-1alpha-regulated vascular
      endothelial growth factor signaling in mice.
AB  - Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula which is
      widely used clinically. In this study, we investigated the effects of an aqueous
      (HJDTaq) and an ethanolic (HJDTet) extract of HJDT on chronic brain injury after
      focal cerebral ischemia in mice. The ischemia was induced by occlusion of the
      right middle cerebral artery for 30 min. HJDTaq (4 g/kg) and HJDTet (200, 400,
      800 mg/kg) were orally administered for 21 d from day 7 before ischemia to day 14
      after ischemia. The survival rate decreased to less than 50% at 35 d after
      ischemia. HJDTet at 400 mg/kg increased the survival rate. HJDTaq (4 g/kg) and
      HJDTet (400, 800 mg/kg) significantly attenuated the neurological dysfunction,
      brain atrophy and infarct volume after ischemia. There were few cells positive
      for CD31, hypoxia-inducible-factor-1alpha (HIF-1alpha), vascular endothelial
      growth factor (VEGF) and Flk-1 in the sham control. After ischemia, the number
      increased. HJDTaq (4 g/kg) and HJDTet (400 or 800 mg/kg) further increased the
      numbers of CD31, HIF-1alpha, VEGF and Flk-1-positive cells in the ischemic
      hemisphere. We conclude that HJDTaq and HJDTet have neuroprotective effects on
      chronic brain injury after focal cerebral ischemia and lead to accelerated
      angiogenesis by HIF-1alpha-regulated VEGF signaling.

PMID- 22382322
TI  - Prediction of percutaneous absorption in human using three-dimensional human
      cultured epidermis LabCyte EPI-MODEL.
AB  - The objective of this study is to establish a relationship of the skin
      penetration parameters between the three-dimensional cultured human epidermis
      LabCyte EPI-MODEL (LabCyte) and hairless mouse (HLM) skin penetration in vitro
      and to predict the skin penetration and plasma concentration profile in human.
      The skin penetration experiments through LabCyte and HLM skin were investigated
      using 19 drugs that have a different molecular weight and lipophilicity. The
      penetration flux for LabCyte reached 30 times larger at maximum than that for HLM
      skin. The human data can be estimated from the in silico approach with the
      diffusion coefficient (D), the partition coefficient (K) and the skin surface
      concentration (C) of drugs by assuming the bi-layer skin model for both LabCyte
      and HLM skin. The human skin penetration of beta-estradiol, prednisolone,
      testosterone and ethynylestradiol was well agreed between the simulated profiles
      and in vitro experimental data. Plasma concentration profiles of beta-estradiol
      in human were also simulated and well agreed with the clinical data. The present
      alternative method may decrease human or animal skin experiment for in vitro skin
      penetration.

PMID- 22382323
TI  - Fenretinide ameliorates insulin resistance and fatty liver in obese mice.
AB  - Fenretinide (FEN), a ligand of retinol binding protein 4 (RBP4), has been
      suggested as a measure to reduce insulin resistance and its associated disorders
      such as obesity, and fatty liver by reducing serum RBP4. We investigated whether
      there is another possible mechanism by which fenretinide reduces insulin
      resistance and fatty liver in genetically obese (ob/ob) mice. Male obese mice fed
      a high-fat diet (45% of calories from fat) were divided into two groups (n=13
      each). One (FEN) received fenretinide (20 mg/kg body weight, intraperitoneally)
      and the other (O) received vehicle three times weekly for 24 d. C57BL/6J mice fed
      a normal-fat diet (16% of calories from fat) were used as a control (C; n=13). No
      changes in fat weight and serum leptin level could be observed in FEN mice. Lower
      plasma RBP4 was observed in FEN mice compared with O mice. Fenretinide improved
      whole-body insulin sensitivity based on glucose and insulin tolerance tests and
      the homeostasis model assessment of insulin resistance. Fenretinide decreased the
      plasma lipid (triglyceride, cholesterol, and free-fatty acid) levels, hepatic TG
      level, and histological steatosis score. The mechanism by which fenretinide
      prevents fatty liver may be explained by an increased plasma adiponectin level,
      increased activation of hepatic AMP-activated protein kinase, and the expression
      of peroxisome proliferator-activated protein-alpha and peroxisomal acyl-CoA
      oxidase, which promote fat oxidation. FEN alleviated insulin resistance and fatty
      liver in obese mice and thus may act as an anti-lipidemic and anti-diabetic drug.

PMID- 22382324
TI  - Role of 5-hydroxytryptamine2C receptors in marble-burying behavior in mice.
AB  - We examined the role of 5-hydroxytryptamine(2C) (5-HT(2C)) receptors in marble
      burying behavior in mice. When administered alone, the selective 5-HT(2C) agonist
      WAY161503 (3 mg/kg) inhibited marble-burying behavior. Moreover, the selective 5
      HT(2C) antagonist SB242084 (3 mg/kg) reversed the inhibition of marble-burying
      behavior by 2,5-dimethoxy-4-iodoamphetamine (DOI) (1 mg/kg) or WAY161503 (3
      mg/kg). Similarly, SB242084 (1 mg/kg) reversed the inhibition of marble-burying
      behavior by fluvoxamine (30 mg/kg) or paroxetine (3 mg/kg). These results suggest
      that 5-HT(2C) receptors play a role in marble-burying behavior in mice.

PMID- 22382325
TI  - Interactions of thyroid hormone receptor with Ku proteins and interleukin
      enhancer binding factor 3 modulate the promoter activity of thyroid-stimulating
      hormone alpha.
AB  - We previously identified Ku proteins and interleukin enhancer binding factor 3
      (ILF3) as cofactors for the nuclear receptor farnesoid X receptor and liver
      receptor homolog-1, respectively. Here we provide further evidence that these
      cofactors modulate the promoter activity of the nuclear receptor thyroid hormone
      receptor (TR) target gene, thyroid-stimulating hormone alpha (TSHalpha), which is
      negatively regulated by the TR ligand triiodothyronine (T(3)). Ku proteins
      suppressed TSHalpha promoter activity independent of T(3), whereas ILF3 enhanced
      TSHalpha activity, especially in the presence of T(3). Taken together, our
      results suggest that Ku proteins and ILF3 function as co-regulators for TR
      mediated TSHalpha expression.

PMID- 22382326
TI  - Biochemical characterization of novel lignans isolated from the wood of Taxus
      yunnanensis as effective stimulators for glycogen synthase kinase-3beta and the
      phosphorylation of basic brain proteins by the kinase in vitro.
AB  - The stimulatory and inhibitory effects of several compounds and lignans isolated
      from the water extract of Taxus yunnanensis on the phosphorylation of three
      functional brain proteins (bovine myelin basic protein (bMBP), recombinant human
      tau protein (rhTP) and rat collapsin response mediator protein-2 (rCRMP-2)) by
      glycogen synthase kinase-3beta (GSK-3beta) were quantitatively compared in vitro,
      using (-)-epigallocatechin-3-gallate [(-)EGCG] as a positive control. We found
      that (i) three selected Taxus lignans [(3S,4R)-4'-hydroxy-6,3'-dimethoxyisoflavan
      4-ol,(7R)-7-hydroxytaxiresinol and tanegool] highly stimulated the
      autophosphorylation of GSK-3beta and the GSK-3beta-mediated phosphorylation of
      two basic brain proteins [bMBP (pI=11.3) and rhTP (pI=8.2)], but inhibited dose
      dependently the phosphorylation of an acidic protein (rCRMP-2, pI=6.0) by the
      kinase; (ii) these three Taxus lignans showed binding-affinities with bMBP as
      well as rhTP, but had low affinities with rCRMP-2; (iii) the binding of tanegool
      and (7R)-7-hydroxytaxiresinol to these two basic proteins induced their novel
      potent phosphorylation sites for GSK-3beta; and (iv) these three Taxus lignans,
      but not EGCG, induced Tyr-phosphorylation of GSK-3beta in vitro. These results
      provided here suggest that (i) these three Taxus lignans act as novel effective
      activators for GSK-3beta and the GSK-3beta-mediated phosphorylation of their
      binding basic proteins (rhTP and bMBP); and (ii) tanegool (IC(50)=1 MUM) is an
      effective inhibitor for the phosphorylation of rCRMP-2 by the kinase in vitro.

PMID- 22382327
TI  - Functional characterization of allelic variants of polymorphic human cytochrome
      P450 2A6 (CYP2A6*5, *7, *8, *18, *19, and *35).
AB  - Cytochrome P450 2A6 (CYP2A6) catalyzes important metabolic reactions of many
      xenobiotic compounds, including coumarin, nicotine, cotinine, and clinical drugs.
      Genetic polymorphisms of CYP2A6 can influence its metabolic activities. This
      study analyzed the functional activities of six CYP2A6 allelic variants
      (CYP2A6*5, *7, *8, *18, *19, and *35) containing nonsynonymous single-nucleotide
      polymorphisms. Recombinant variant enzymes of CYP2A6*7, *8, *18, *19, and *35
      were successfully expressed in Escherichia coli and purified. However, a P450
      holoenzyme spectrum was not detected for the CYP2A6*5 allelic variant (G479V).
      Structural analysis shows that the G479V mutation may alter the interaction
      between the A helix and the F-G helices. Enzyme kinetic analyses indicated that
      the effects of mutations in CYP2A6 allelic variants on drug metabolism are
      dependent on the substrates. In the case of coumarin 7-hydroxylation, CYP2A6*8
      and *35 displayed increased K(m) values whereas CYP2A6*18 and *19 showed
      decreased k(cat) values, which resulted in lower catalytic efficiencies
      (k(cat)/K(m)). In the case of nicotine 5-oxidation, the CYP2A6*19 variant
      exhibited an increased K(m) value, whereas CYP2A6*18 and *35 showed much greater
      decreases in k(cat) values. These results suggest that individuals carrying these
      allelic variants are likely to have different metabolisms for different CYP2A6
      substrates. Functional characterization of these allelic variants of CYP2A6 can
      help determine the importance of CYP2A6 polymorphisms in the metabolism of many
      clinical drugs.

PMID- 22382328
TI  - Caffeine increases the antitumor effect of Cisplatin in human hepatocellular
      carcinoma cells.
AB  - Caffeine is thought to increase the antitumor effect of cisplatin or DNA-damaging
      agents because it is known that caffeine inhibits DNA repair. Caffeine-assisted
      chemotherapy has been used in the treatment of osteosarcomas. In addition, there
      are several reports about combination chemotherapy with caffeine for certain
      malignancies other than osteosarcomas. However, there are no reports that show
      the utility of combination chemotherapy with caffeine for hepatocellular
      carcinoma (HCC). We examined the combined effects of caffeine and cisplatin in
      human HCC cell lines, and screened for a more effective administration method of
      caffeine in vitro. Human HCC cell lines (HepG2, HLF, HuH-7, and Li-7) were
      exposed to caffeine (0-0.5 mM) and cisplatin (0-1.2 MUg/mL) for 72 h, either
      alone or in combination. Cell numbers were measured by WST-8 assay, and cell
      apoptosis was determined by annexin V-fluorescein isothiocyanate (FITC)/propidium
      iodide (PI) binding assay. As a result, caffeine increased the antitumor effect
      of cisplatin on cell proliferation and cell apoptosis in the HCC cell lines.
      Moreover, this effect was dependent on the amount of exposure to caffeine. These
      results suggest that caffeine-assisted chemotherapy is useful for HCC treatment.

PMID- 22382329
TI  - Restriction of mast cell proliferation through hyaluronan synthesis by co
      cultured fibroblasts.
AB  - Appropriate culture models for tissue mast cells are required to determine how
      they are involved in regulation of local immune responses. We previously
      established a culture model for cutaneous mast cells, in which bone marrow
      derived immature mast cells were co-cultured with Swiss 3T3 fibroblasts in the
      presence of stem cell factor. In this study, we focused on the roles of
      hyaluronan, which is produced by the feeder fibroblasts and forms the
      extracellular matrix during the co-culture period. Hyaluronan synthesis was found
      to be mediated by hyaluronan synthase 2 (HAS2) expressed in Swiss 3T3 cells. A
      decreases in the amount of hyaluronan, which was achieved by retroviral
      expression of short hairpin RNA for Has2 or by addition of hyaluronidase,
      significantly enhanced the proliferation of the cultured mast cells without any
      obvious effects on their maturation. Although we previously demonstrated that
      CD44 is required for proliferation of cutaneous mast cells, the deficiency of
      hyaluronan did not affect the proliferation of the cultured mast cells that lack
      CD44. These findings suggest that the extracellular matrix containing hyaluronan
      may have a potential to restrict proliferation of cutaneous mast cells in a CD44
      independent manner.

PMID- 22382330
TI  - Identification of enzymes responsible for the N-oxidation of darexaban
      glucuronide, the pharmacologically active metabolite of darexaban, and the
      glucuronidation of darexaban N-oxides in human liver microsomes.
AB  - Darexaban maleate is a novel oral direct factor Xa inhibitor. Darexaban
      glucuronide (YM-222714) was the major component in plasma after oral
      administration of darexaban to humans and is the pharmacologically active
      metabolite. Additionally, YM-222714 N-oxides were detected as minor metabolites
      in human plasma and urine. It is possible that YM-222714 N-oxides are formed by
      the N-oxidation of YM-222714 and/or the glucuronidation of darexaban N-oxides (YM
      542845) in vivo. The former reaction is the pharmacological inactivation process.
      In this study, we identified the human enzymes responsible for YM-222714 N
      oxidation and the uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT)
      isoforms involved in YM-542845 glucuronidation in vitro. YM-222714 N-oxidation
      activity was detected in human liver microsomes (HLM), but not in human
      intestinal microsomes. In HLM, YM-222714 N-oxidation activities were
      significantly correlated with flavin-containing monooxygenase (FMO) marker enzyme
      activities (p<0.001) and inhibited by methimazole, a typical inhibitor of FMOs.
      Recombinant human FMO3 and FMO1 were capable of efficiently catalyzing YM-222714
      N-oxidation, but not FMO5 or any recombinant human cytochrome P450 (CYP)
      isoforms. Considering the mRNA expression levels of FMO isoforms in human liver,
      these results strongly suggest that YM-222714 N-oxidation in HLM is mainly
      catalyzed by FMO3. In HLM, YM-542845 glucuronidation was strongly inhibited by
      typical substrates for UGT1A8, UGT1A9, and UGT1A10. Recombinant human UGT1A7,
      UGT1A8, UGT1A9, and UGT1A10 were capable of catalyzing YM-542845 glucuronidation,
      and UGT1A9 exhibited the highest intrinsic clearance. Considered together with
      the expression levels of UGT isoforms in human liver, these results strongly
      suggest that YM-542845 glucuronidation in HLM is mainly catalyzed by UGT1A9.

PMID- 22382331
TI  - Distribution of prolylhydroxyproline and its metabolites after oral
      administration in rats.
AB  - Prolylhydroxyproline (Pro-Hyp), which is derived from collagen hydrolysate, has
      been shown to be beneficial for skin and joint health. However, little is known
      about the distribution of Pro-Hyp in these tissues. In the present study, we
      investigated the biodistribution of orally administered [(14)C]Pro-Hyp in rats.
      Whole-body autoradiography at 30 min after administration of [(14)C]Pro-Hyp
      showed that radioactivity is widely distributed in tissues including skin and
      articular cartilage, with the highest level of radioactivity observed in the
      gastric and intestinal walls. Incorporation of radioactivity into cells known to
      respond to Pro-Hyp such as dermal fibroblasts, synovial cells, chondrocytes,
      osteoblasts, and osteoclasts was observed. The chemical form of [(14)C]Pro-Hyp
      derived radioactivity detected in the tissues was investigated by thin layer
      chromatography. The radioactive constituents in cartilage extract were two
      proline-modified peptides (56%), intact Pro-Hyp (5%), and two nonpeptide
      metabolites (28%). Similar results were obtained for skin and bone marrow. Plasma
      analysis at 3 to 30 min post-dose suggested that the majority of Pro-Hyp is
      modified in its proline residue by a first-pass effect without peptide bond
      hydrolysis. In conclusion, we demonstrated that Pro-Hyp is partly distributed in
      observed tissues including skin and cartilage in its intact form, which might be
      responsible for its biological functions.

PMID- 22382332
TI  - Acylated kaempferol glycosides from Laurus nobilis leaves and their inhibitory
      effects on Na+/K+-adenosine triphosphatase.
AB  - Na(+)/K(+)-adenosine triphosphatase (ATPase) inhibitors have considerable
      therapeutic potential against some heart diseases like congestive heart failure
      and cardiac arrhythmias. Through bioassay-guided separation of the leaf extract
      of Laurus nobilis, six acylated kaempferol glycosides (compounds 1-6) were
      isolated. Their structures were determined on the basis of spectroscopic analysis
      and comparison with reported data. All the isolates were subjected to in vitro
      bioassays to evaluate their inhibitory activities against Na(+)/K(+)-ATPase from
      porcine cerebral cortex and bacterial growth. These studies led to the
      identification of compounds 1-6 as potent Na(+)/K(+)-ATPase inhibitors, with
      IC(50) values in the range of 4.0 +/- 0.1-10.4 +/- 0.6 MUM. These compounds also
      exhibited a broad spectrum of antibacterial activity. In particular, compounds 4
      and 6 showed potent inhibitory activities against several bacterial strains,
      except Escherichia coli, with minimum inhibitory concentration (MIC) values in
      the range of 0.65-2.08 MUg/mL. Thus, L. nobilis-derived acylated kaempferol
      glycosides may have a potential to be leads for the development of Na(+)/K(+)
      ATPase inhibitors (1-6) and antibacterial agents (4, 6).

PMID- 22382333
TI  - Effects of halogenation on tyrosine phosphorylation and peptide binding to the
      SRC homology 2 domain of lymphocyte-specific protein tyrosine kinase.
AB  - Phosphorylation of tyrosine residues by protein tyrosine kinases (PTK) and
      phosphotyrosine/Src homology 2 (SH2) domain interactions are crucial not only for
      signal transduction but also for regulation of PTK activity. Tyrosine residues
      also receive nitration and halogenation under oxidative conditions. It has been
      reported that nitration of tyrosine residue caused peptides to be a poor
      substrate for PTK and that nitrotyrosine residues could bind to SH2 domains as a
      phosphotyrosine mimic to activate Src family kinase. However, the effect of
      halogenation on tyrosine phosphorylation or SH2 domain binding is not well
      understood. We examined the phosphorylation of model peptides containing 3
      halotyrosine or 3-nitrotyrosine using typical receptor tyrosine kinase, epidermal
      growth factor receptor (EGFR), and nonreceptor tyrosine kinase, lymphocyte
      specific protein tyrosine kinase (Lck). The EGFR- and Lck-mediated
      phosphorylation was markedly inhibited by tyrosine halogenation. Iodination
      showed the strongest inhibition of the phosphorylation among four types of
      halogenation, and its inhibitory effect was stronger than that of nitration. We
      also examined the effect of iodination and nitration of tyrosine residues on
      binding to the SH2 domain of Lck, using a model peptide containing the phosphoTyr
      Glu-Glu-Ile motif, which has a high affinity for the SH2 domain. The relative
      affinities of the modified peptides whose phosphotyrosine was substituted with
      unphosphorylated tyrosine, 3-nitrotyrosine, and 3-iodotyrosine, and of the model
      peptide were 0.024, 0.26, 1, and 16, respectively. These results suggest that
      tyrosine iodination may have an effect on the phosphorylation or binding to the
      SH2 domain similar to nitration. Tyrosine iodination possibly modulates signal
      transduction, with the potential impairment of cell function.

PMID- 22382334
TI  - Characteristics of diabetic osteopenia in KK-Ay diabetic mice.
AB  - We examined the bone mineral density (BMD) of the proximal region and the mid
      diaphysis of the femur using dual energy X-ray absorption (DXA), the blood
      osteocalcin level and the blood glucose level every five weeks from 8 to 23 weeks
      old in KK-Ay diabetic mice. The BMD of the proximal region after 18 weeks old was
      significantly lower when compared with that at 8 weeks old (p<0.05), whereas
      there was no significant difference in the BMD of the mid-diaphysis at each week.
      The BMD of the proximal region at 18 weeks old was significantly lower than that
      in ddY mice, used as controls (p<0.05). The blood osteocalcin level at 18 weeks
      old was significantly lower than that at 8 weeks old and that in 18-week-old ddY
      mice (p<0.05). There was significant negative correlation between the blood
      glucose level and the BMD of the proximal region (r=-0.64, p<0.05). These results
      suggest that type 2 diabetes exerts an influence only on spongy bone, not on
      cortical bone, and that the BMD in the proximal region of the femur seems to be
      affected by blood glucose level, parallel with the progression of diabetes,
      through the blood osteocalcin level. In the present study, we show the
      characteristics of diabetic osteopenia in KK-Ay mice, an animal model of type 2
      diabetes.

PMID- 22382335
TI  - Anticitrullinated protein antibody, but not its titer, is a predictor of
      radiographic progression and disease activity in rheumatoid arthritis.
AB  - OBJECTIVE: To study the contribution of anticitrullinated protein antibody
      (ACPA), and especially of its titer, to radiographic progression and disease
      activity in rheumatoid arthritis (RA). METHODS: Patients with RA (n = 396) who
      attended a Japanese clinic within 2 years after disease onset were divided into
      the following groups according to second-generation (ACPA-2) ACPA titer on their
      first visit: negative (0-4.4 U/ml; n = 115), low-positive (4.5-121 U/ml; n =
      141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were
      further subdivided into lowest (4.5-32 U/ml), low (33-121 U/ml), high (122-277
      U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease
      modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics.
      Subsequent radiographic progression and disease activity for 2 years were
      prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and
      28-joint Disease Activity Score (DAS28). RESULTS: After treatment with DMARD, the
      disease activity (including number of swollen joints, number of tender joints,
      duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C
      reactive protein) was significantly decreased in all patient groups. Disease
      activity and radiographic progression as revealed by the change in SHS remained
      relatively higher in the ACPA-2 low- and high-positive groups as compared with
      the ACPA-2-negative group. The relationship between the titer of ACPA-2 at
      baseline and subsequent radiographic progression was not exactly linear, and the
      extent of disease activity or radiographic progression was similar between ACPA-2
      low- and high-positive groups and also between ACPA-2 lowest- and highest
      positive quartile groups. The results were demonstrable in cumulative SHS
      probability plots, and also repeatable in seronegative patients, which indicated
      that the titer of ACPA-2 is not a predictor of disease activity or radiographic
      progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml,
      showed minimal radiographic progression. CONCLUSION: Presence of ACPA-2, but not
      its titer, at baseline is a predictor of radiographic progression or disease
      activity, where radiographic progression is minimal in ACPA-2-negative patients.

PMID- 22382336
TI  - Detection of HTLV-1 in the labial salivary glands of patients with Sjogren's
      syndrome: a distinct clinical subgroup?
AB  - OBJECTIVE: To examine whether patients with Sjogren's syndrome (SS) can be
      distinguished based on the expression of human T cell lymphotrophic virus type I
      (HTLV-1) and, if so, whether the subgroups differ in their clinical features and
      serological measures. METHODS: Polymerase chain reaction (PCR) and nested PCR
      were used to amplify viral DNA from peripheral blood mononuclear cells (PBMC) in
      53 patients with SS, using primers from the HTLV-1 pX, p19, pol, and tax regions.
      Minor salivary gland biopsy specimens from 33 patients with SS were examined for
      the presence of HTLV-1 p19 or tax proteins immunohistochemically. The
      sociodemographic, glandular, and extraglandular manifestations, and laboratory
      findings including autoantibodies, complement, and immunoglobulin levels, were
      analyzed. RESULTS: The HTLV-1 tax gene was detected in PBMC samples from 2 of 53
      patients (3.8%), whereas the HTLV-1 pX, p19, and pol genes were not expressed. As
      well, 100% of PBMC samples from 4 family members of patients in whom the tax gene
      was detected also expressed the tax gene. Immunohistochemical staining for HTLV-1
      p19 and tax was seen in 10 out of 33 (30.3%) patients with SS each. Overall, 14
      (42.4%) patients expressed HTLV-1 p19 or tax proteins, and they had lower
      rheumatoid factor and C3 levels (p = 0.015 and p = 0.005, respectively) and
      higher lymphocyte counts (p = 0.016). The prevalence of glandular and
      extraglandular manifestations did not differ between the HTLV-1-positive and
      negative patients. CONCLUSION: Our findings suggest that HTLV-1 in the salivary
      glands is involved in the pathogenesis of a subpopulation of SS, and HTLV-1
      associated SS might have different immunological patterns than idiopathic SS.

PMID- 22382337
TI  - Anticitrullinated protein antibodies and radiological progression in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: The aim of the study was to investigate whether determination of
      anticitrullinated protein antibodies (ACPA) provides predictive information on
      severity of disease course and joint destruction in children with juvenile
      idiopathic arthritis (JIA). METHODS: Sera from 74 children with JIA were examined
      for ACPA using the ELISA test. To assess joint destruction, plain radiographs of
      both hands were scored twice according to the Steinbrocker scale: at the
      beginning of observation and after 8.9 to 15.2 months (median 11.5 months) of the
      followup. Correlations between ACPA serum levels and the disease characteristics
      (type of JIA onset, disease activity, disease duration, radiological status) were
      investigated. RESULTS: Twenty-six out of 74 examined children with JIA (35.0%)
      were ACPA-positive [> 5 relative units (RU)/ml]. ACPA were present in all types
      of JIA onset, including 36.6% of children with early stage JIA (disease duration
      < 6 months). All of the IgM-rheumatoid factor (RF)-positive children with
      polyarticular type of JIA onset were simultaneously positive for ACPA. ACPA
      levels correlated positively with disease activity at the beginning of the study
      (rho = 0.7196; p < 0.0001) and after followup (rho = 0.2485; p = 0.0486). Disease
      duration did not significantly affect ACPA serum levels. ACPA levels correlated
      positively with radiological joint destruction in children with JIA, both at the
      beginning of the study (rho = 0.4599; p = 0.0004) and after the followup period
      (rho = 0.5523; p < 0.0001). CONCLUSION: ACPA were superior to IgM-RF in
      diagnosing JIA and provided predictive information on severity of disease course
      and radiological outcome.

PMID- 22382338
TI  - Are cognitive and olfactory dysfunctions in neuropsychiatric lupus erythematosus
      dependent on anxiety or depression?
AB  - OBJECTIVE: Depressed mood and cognitive impairments are common findings in
      systemic lupus erythematosus (SLE) and frequently coexist. We assessed the
      neuropsychological functioning of patients with SLE and investigated its
      association with psychopathological symptoms. METHODS: A total of 85 patients
      with SLE (28 with neuropsychiatric syndromes: NPSLE) and 85 healthy control
      subjects with similar demographic characteristics were asked to perform a series
      of neuropsychological tests. A self-report questionnaire (the Hospital Anxiety
      and Depression Scale) was used to screen for psychopathology symptoms. Patients
      with SLE underwent a neurological examination. RESULTS: Patients with NPSLE were
      more depressed and were more frequently impaired in cognitive and olfactory
      functions than controls or non-NPSLE patients. The NPSLE group remained
      statistically different from the other 2 groups on a series of neuropsychological
      measures (the Auditory Verbal Learning Test, Trail Making Test - Part A, Nine
      Hole Peg Test, and Brief Smell Identification Test) even after control for
      elevated anxiety and depressed mood. Non-NPSLE and control groups were not
      significantly different regarding either psychopathological symptoms or
      neuropsychological functioning. CONCLUSION: Verbal memory, psychomotor speed, and
      olfaction are particularly vulnerable to dysfunction in NPSLE; impairment in
      these neuropsychological domains is not completely explained by psychopathology
      symptoms.

PMID- 22382339
TI  - Interpretation of metaanalyses: pitfalls should be more widely recognized.

PMID- 22382340
TI  - Challenges in evaluating an Arthritis Self-Management Program for people with hip
      and knee osteoarthritis in real-world clinical settings.
AB  - OBJECTIVE: To evaluate the influence of a 6-week Arthritis Self-Management
      Program (ASMP) on health-related quality of life (HRQOL) and self-management
      skills in clinical settings. METHODS: Individuals with hip or knee osteoarthritis
      referred to orthopedic surgeons or rheumatologists at 6 hospitals in Victoria,
      Australia, were recruited. In a randomized controlled trial, participants
      received the Stanford ASMP and self-help book (intervention) or book only
      (control). Assessments included the Assessment of Quality of Life instrument
      (AQoL; range -0.04 to 1.00) and Health Education Impact Questionnaire (heiQ;
      range 1-6) at baseline and up to 12 months. The primary outcome was HRQOL at 12
      months (assessed using the AQoL). RESULTS: Recruitment was concluded early due to
      persistent challenges including infrequent referrals and patient inability or
      disinterest in participating. Of 1125 individuals screened, only 120 were
      randomized (control, n = 62; intervention, n = 58). Seven ASMP were conducted
      while 18 scheduled ASMP were cancelled. Forty-four of 58 intervention group
      participants received the intervention as allocated (76%); all control group
      participants were sent the book (100%). Ninety-four participants (78%) completed
      12-month assessments (control, 90%; intervention, 66%). There was no difference
      in HRQOL at 12 months (adjusted mean difference -0.02, 95% CI -0.09 to 0.05). At
      6 weeks, the intervention group reported higher heiQ skill and technique
      acquisition scores (adjusted mean difference 0.29, 95% CI 0.04 to 0.55); however,
      this dissipated by 3 months. CONCLUSION: Significant challenges hampered this
      evaluation of the ASMP. The observed lack of enthusiasm from potential referrers
      and patients raises doubts about the practicality of this intervention in real
      world settings. (ANZCTR Clinical Trials Registry no. ACTRN12606000174583).

PMID- 22382342
TI  - Home parenteral nutrition in patients with systemic sclerosis: a retrospective
      review of 12 cases.
AB  - OBJECTIVE: To evaluate the effect of home total parenteral nutrition (HTPN) on
      the nutritional and functional status of patients with systemic sclerosis (SSc).
      METHODS: Retrospective review of SSc patients from the HTPN database at the
      University Health Network, Toronto, Canada, from 1998 to 2010. RESULTS: In total
      12 subjects (9 females, 3 males) with SSc were identified. At initiation of HTPN,
      the age was 48.75 +/- 3.94 years and the median body mass index was 16.8 kg/m(2)
      (range 12.3-21.3). This significantly increased to 18.3 kg/m(2) (17.0-21.7) at 6
      months and to 19.7 kg/m(2) (17.0-24.6) at 12 months. The mean Karnofsky score at
      baseline was 58.00 +/- 3.27, and the score at 12 months of 39.00 +/- 13.29 did
      not change significantly. CONCLUSION: HTPN improved the nutritional status of
      these patients with SSc but it did not improve their functional status.

PMID- 22382341
TI  - Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment
      of patients with rheumatoid arthritis inadequately controlled by methotrexate.
AB  - OBJECTIVE: To evaluate efficacy and safety of CE-224,535, a selective P2X(7)
      receptor antagonist, versus placebo, in patients with active rheumatoid arthritis
      (RA) and inadequate response to methotrexate (MTX). METHODS: In our phase IIA
      study (ClinicalTrials.gov no. NCT00628095; A6341009), patients aged >= 18 years
      with active RA were randomized to receive either CE-224,535 (500 mg bid) or
      placebo for 12 weeks; all patients continued a stable background dose of >= 7.5
      mg MTX. RESULTS: The American College of Rheumatology 20% (ACR20) response rate
      (primary efficacy endpoint) was not significantly different from placebo for CE
      224,535 (34.0% vs 36.2%; p = 0.591) at Week 12, or at any timepoint over the 12
      week treatment period. There was no significant difference at Week 12 for the
      ACR20 response rate following subgroup analyses by age, sex, baseline disease
      activity, baseline duration of disease, geographic region, or concomitant use of
      steroids. ACR50/ACR70 response rates and change from baseline in Disease Activity
      Score 28-joint C-reactive protein (DAS28-3-CRP) and Health Assessment
      Questionnaire-Disability Index for CE-224,535 were not significant at Week 12
      versus placebo. Treatment-emergent adverse events (AE) were reported by 62.3% (CE
      224,535) and 55.3% (placebo) of patients; the most common AE were nausea (11.3%,
      CE-224,535; 4.3%, placebo) and diarrhea (7.5%, CE-224,535; 4.3%, placebo). The
      proportion of patients discontinuing due to an AE was 9.4% (CE-224,535) and 6.4%
      (placebo); no deaths were reported. Serious AE occurred in 3.8% (CE-224,535) and
      2.1% (placebo) of patients; none was considered treatment-related. CONCLUSION: CE
      224,535 was not efficacious, compared with placebo, for the treatment of RA in
      patients with an inadequate response to MTX. CE-224,535 demonstrated an
      acceptable safety and tolerability profile.

PMID- 22382343
TI  - Epidemiology of systemic sclerosis in a large US managed care population.
AB  - OBJECTIVE: To estimate the incidence and prevalence of systemic sclerosis (SSc)
      in a large US managed care organization (MCO) database. METHODS: Subjects with
      claims-based evidence of SSc (ICD-9-CM code 710.1x) were identified from a health
      plan database. Incidence and prevalence for the period 2003-2008 were calculated.
      RESULTS: The overall age- and sex-adjusted incidence rate (2003-2008) for SSc was
      5.6 cases per 100,000 person-years. The annual prevalence of SSc ranged from 13.5
      in 2003 to 18.4 (per 100,000) in 2008. CONCLUSION: This analysis suggests a
      higher incidence and lower prevalence of SSc in this MCO than those previously
      reported for the United States.

PMID- 22382344
TI  - Short-term risk of total malignancy and nonmelanoma skin cancers with
      certolizumab and golimumab in patients with rheumatoid arthritis: metaanalysis of
      randomized controlled trials.
AB  - OBJECTIVE: To assess the risk of total malignancy and nonmelanoma skin cancers
      (NMSC) in patients with rheumatoid arthritis (RA) receiving certolizumab and
      golimumab through a metaanalysis of data from randomized control trials (RCT).
      METHODS: We systematically reviewed the literature up to May 2011 in Medline
      databases, as well as abstracts from the 2009 and 2010 annual meetings of the
      European League Against Rheumatism and the American College of Rheumatology.
      Mantel-Haenszel method was used to determine a common odds ratio (OR).
      Statistical heterogeneity was assessed by chi-square Q test. We selected only RCT
      including more than 30 RA subjects randomly assigned to an anti-tumor necrosis
      factor (TNF) or a nonbiological disease-modifying antirheumatic drug (DMARD)
      control group. RESULTS: The literature search identified 793 articles; 6 (2 with
      certolizumab and 4 with golimumab) were selected for metaanalysis. A total of
      2710 patients received at least 1 dose of certolizumab or golimumab. For anti-TNF
      treated patients, 18 cancers (excluding NMSC) and 9 NMSC were observed versus 4
      cases of total malignancy and 3 NMSC in control groups. Metaanalysis revealed a
      pooled OR of 1.06 (95% CI 0.39-2.85) for risk of total malignancy and 0.69 (95%
      CI 0.23-2.11) for risk of NMSC with certolizumab and golimumab versus DMARD.
      Heterogeneity was not significant. CONCLUSION: Metaanalysis of RCT of golimumab
      and certolizumab did not find an increased risk of total malignancy and NMSC.
      These results must be confirmed with longterm extension studies and registry
      studies, and careful monitoring remains mandatory.

PMID- 22382345
TI  - Low socioeconomic status is associated with cardiovascular risk factors and
      outcomes in systemic lupus erythematosus.
AB  - OBJECTIVE: Accelerated atherosclerosis is a major cause of death in systemic
      lupus erythematosus (SLE), yet little is known about the effect of socioeconomic
      status. We investigated whether education or income levels are associated with
      cardiovascular risk factors and outcomes in SLE. METHODS: Our study involved a
      longitudinal cohort of all patients with SLE enrolled in the Hopkins Lupus Cohort
      from 1987 through September 2011. Socioeconomic status was measured by education
      level (>= 12 years or < 12) and income tertiles (> $60,000, $25,000-$60,000, or <
      $25,000). RESULTS: A total of 1752 patients with SLE were followed prospectively
      every 3 months. There were 1052 whites and 700 African Americans. Current
      smoking, obesity, hypertension, and diabetes mellitus were more common in African
      Americans (p < 0.01 for all), but there was no statistical difference in the
      frequency of myocardial infarction or stroke. In multivariate analyses stratified
      by ethnicity, low income was strongly associated with most traditional
      cardiovascular risk factors in whites, but only with smoking and diabetes in
      African Americans. In whites, low income increased the risk of both myocardial
      infarction (OR 3.24, 95% CI 1.41-7.45, p = 0.006) and stroke (OR 2.85, 95% CI
      1.56-5.21, p = 0.001); in African Americans, these relationships were not seen.
      Low education, in contrast, was associated with smoking in both ethnic groups.
      CONCLUSION: Low income, not low education, is the socioeconomic status variable
      associated with cardiovascular risk factors and events. This association is most
      clearly demonstrable in whites.

PMID- 22382346
TI  - Progression of esophageal dysmotility in systemic sclerosis.
AB  - OBJECTIVE: To longitudinally evaluate esophageal dysmotility (ED) in patients
      with limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic
      sclerosis (dcSSc). METHODS: We performed a retrospective review of all adult
      patients with SSc seen between 1995 and 2008. Patients were included if they had
      undergone 2 or more esophageal transit scintigraphy (ETS) studies at least 1 year
      apart. Data from 382 ETS studies of 102 patients with SSc were analyzed. Eighty
      patients had lcSSc and 22 patients had dcSSc. A grading system was used to
      quantify the degree of esophageal dysfunction, ranging from grade 0 (normal) to
      grade 3 (severe hypomotility). Change in esophageal motility over time was
      evaluated and compared between the limited and diffuse subtypes. RESULTS: Sixty
      eight patients (66.7%) had an abnormal ETS study at any time. Of patients with
      dcSSc, 95.4% had an abnormal ETS study, compared to 58.5% of patients with lcSSc.
      dcSSc and regurgitation were independent risk factors for ED. There was no
      association between the presence of anticentromere antibodies or
      antitopoisomerase (anti-Scl-70) antibodies and an abnormal ETS study. Esophageal
      motility in patients with dcSSc worsened in 96% of cases compared with only 58.8%
      in those with lcSSc. CONCLUSION: ED is more frequent in patients with dcSSc than
      in those with lcSSc, and is more likely to deteriorate over time. Given the
      potential associated risks of erosive esophagitis, Barrett's esophagus, and
      esophageal cancer in patients with SSc, routine screening and monitoring for ED
      is advised.

PMID- 22382347
TI  - Occupational risk factors for systemic lupus erythematosus: a nationwide study
      based on hospitalizations in Sweden.
AB  - OBJECTIVE: To investigate possible associations between occupation and
      hospitalization for systemic lupus erythematosus (SLE) in a nationwide study.
      METHODS: A nationwide database was constructed in Sweden by linking the Swedish
      Census to the Hospital Discharge Register to obtain data on all first
      hospitalizations with a primary or secondary diagnosis of SLE in adults during
      the study period (1970 to 2008). Standardized incidence ratios (SIR) and 95% CI
      were calculated for different occupations. Two cohorts were defined based on
      occupational titles recorded in Swedish census data in 1970 and 1980. RESULTS: A
      total of 8921 male and 42290 female hospitalizations for SLE were retrieved in
      individuals aged over 15 years. High education (> 12 yrs) was associated with a
      lower risk of hospitalization for SLE among both women (SIR = 0.73) and men (SIR
      = 0.72). Among men with the same occupation in 2 consecutive censuses, increased
      risks (SIR) > 2.0 were present among artistic workers (2.52); shop managers and
      assistants (3.63); miners and quarry workers (6.04); shoe and leather workers
      (6.93); plumbers (2.21); other construction workers (2.08); glass, ceramic and
      tile workers (4.43); chimney sweeps (4.54); and military personnel (3.01). Among
      women with the same occupation in 2 consecutive censuses, no occupation was
      associated with SIR > 2.0. CONCLUSION: Occupation may carry significantly
      increased risk of hospital admission for SLE. Especially among men, several
      occupations were associated with increased risks for SLE.

PMID- 22382348
TI  - Differences between male and female systemic lupus erythematosus in a multiethnic
      population.
AB  - OBJECTIVE: Male patients with systemic lupus erythematosus (SLE) are thought to
      be similar to female patients with SLE, but key clinical characteristics may
      differ. Comparisons were made between male and female patients with SLE in the
      Hopkins Lupus Cohort. METHODS: A total of 1979 patients in the Hopkins Lupus
      Cohort were included in the analysis. RESULTS: The cohort consisted of 157 men
      (66.2% white, 33.8% African American) and 1822 women (59.8% white, 40.2% African
      American). The mean followup was 6.02 years (range 0-23.73). Men were more likely
      than women to have disability, hypertension, thrombosis, and renal,
      hematological, and serological manifestations. Men were more likely to be
      diagnosed at an older age and to have a lower education level. Women were more
      likely to have malar rash, photosensitivity, oral ulcers, alopecia, Raynaud's
      phenomenon, or arthralgia. Men were more likely than women to have experienced
      end organ damage including neuropsychiatric, renal, cardiovascular, peripheral
      vascular disease, and myocardial infarction, and to have died. In general,
      differences between males and females were more numerous and striking in whites,
      especially with respect to lupus nephritis, abnormal serologies, and thrombosis.
      CONCLUSION: Our study suggests that there are major clinical differences between
      male and female patients with SLE. Differences between male and female patients
      also depend on ethnicity. Future SLE studies will need to consider both ethnicity
      and gender to understand these differences.

PMID- 22382350
TI  - Arterial spin labelling: final steps to make it a clinical reality.
AB  - Since its inception in the early 1990s, arterial spin labelling (ASL) has been
      developed in numerous variants. Tremendous improvements in both pulse sequences
      and hardware have allowed improved image quality and reduced scan time, to the
      point where the technique might be ready for clinical application. However,
      although now routinely used in research centres and universities, its application
      in daily clinical routine remains restricted to a few centres. Its popularity in
      magnetic resonance imaging (MRI) research centres and among physicists may have
      contributed to the lack of enthusiasm from the clinical community, as the variety
      of possible sequences available might deter even the most die-hard technology
      driven neuroradiologist from using this technique. Therefore, a joint action
      directed towards the harmonisation of all the existing ASL pulse sequences and
      the development of a reliable and common post-processing pipeline to provide
      guidance for the major MRI manufacturers was recently endeavoured and dubbed the
      'ASL Network' ( http://www.asl-network.org ). This network was established to
      provide a communication platform among physicists, engineers and clinicians who
      are keen to see this technique finally make it to daily clinical practice.
      Finally, a networking European Grant from the COST Office was secured to help
      fund some of the activities of the ASL Network, in particular as they pertain to
      the application of ASL in dementia (
      http://www.cost.eu/domains_actions/bmbs/Actions/BM1103 ). Here, both the ASL
      Network and the COST Action are described, with their respective goals and
      aspirations.

PMID- 22382352
TI  - CT scans: balancing health risks and medical benefits.

PMID- 22382353
TI  - Laue crystal structure of Shewanella oneidensis cytochrome c nitrite reductase
      from a high-yield expression system.
AB  - The high-yield expression and purification of Shewanella oneidensis cytochrome c
      nitrite reductase (ccNiR) and its characterization by a variety of methods,
      notably Laue crystallography, are reported. A key component of the expression
      system is an artificial ccNiR gene in which the N-terminal signal peptide from
      the highly expressed S. oneidensis protein "small tetraheme c" replaces the wild
      type signal peptide. This gene, inserted into the plasmid pHSG298 and expressed
      in S. oneidensis TSP-1 strain, generated approximately 20 mg crude ccNiR per
      liter of culture, compared with 0.5-1 mg/L for untransformed cells. Purified
      ccNiR has nitrite and hydroxylamine reductase activities comparable to those
      previously reported for Escherichia coli ccNiR, and is stable for over 2 weeks in
      pH 7 solution at 4  degrees C. UV/vis spectropotentiometric titrations and
      protein film voltammetry identified five independent one-electron reduction
      processes. Global analysis of the spectropotentiometric data also allowed
      determination of the extinction coefficient spectra for the five reduced ccNiR
      species. The characteristics of the individual extinction coefficient spectra
      suggest that, within each reduced species, the electrons are distributed among
      the various hemes, rather than being localized on specific heme centers. The
      purified ccNiR yielded good-quality crystals, with which the 2.59-A-resolution
      structure was solved at room temperature using the Laue diffraction method. The
      structure is similar to that of E. coli ccNiR, except in the region where the
      enzyme interacts with its physiological electron donor (CymA in the case of S.
      oneidensis ccNiR, NrfB in the case of the E. coli protein).

PMID- 22382354
TI  - Clinical aspects of common genetic Creutzfeldt-Jakob disease.

PMID- 22382355
TI  - Understanding the solubility of triamino-trinitrobenzene in hydrous
      tetramethylammonium fluoride: a first principles molecular dynamics simulation
      study.
AB  - With the aim to understand the relatively high solubility of 1,3,5-triamino-2,4,6
      trinitrobenzene (TATB), an important energetic material with a high degree of
      inter- and intra-molecular hydrogen bonding, in fluoride anion containing ionic
      liquids (ILs), first principles molecular dynamics simulations in the isobaric
      isothermal ensemble were carried out for a system using hydrous
      tetramethylammonium fluoride as the prototypical solvent. Simulations initiated
      from both molecular TATB and its Meisenheimer complex (i.e., a sigma-complex of
      the fluoride and the electrophilic ring of TATB) yield a Zundel-type complex
      where a proton is shared between an amino group and an F(-) ion, whereas the
      Meisenheimer complex is found to be only transiently stable. An analysis of the
      electronic structure probing the Wannier function centers supports the finding of
      a proton-sharing complex with a three-center four-electron like bond. The Zundel
      type complex also yields an electronic absorption spectrum consistent with the
      experimentally observed color change. This study provides evidence that the
      remarkable solubility of otherwise hard-to-dissolve molecular crystals in ILs can
      be aided by chemical modification of the solute.

PMID- 22382356
TI  - Characterizing a neurodegenerative syndrome: primary progressive apraxia of
      speech.
AB  - Apraxia of speech is a disorder of speech motor planning and/or programming that
      is distinguishable from aphasia and dysarthria. It most commonly results from
      vascular insults but can occur in degenerative diseases where it has typically
      been subsumed under aphasia, or it occurs in the context of more widespread
      neurodegeneration. The aim of this study was to determine whether apraxia of
      speech can present as an isolated sign of neurodegenerative disease. Between July
      2010 and July 2011, 37 subjects with a neurodegenerative speech and language
      disorder were prospectively recruited and underwent detailed speech and language,
      neurological, neuropsychological and neuroimaging testing. The neuroimaging
      battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]
      fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography
      scanning. Twelve subjects were identified as having apraxia of speech without any
      signs of aphasia based on a comprehensive battery of language tests; hence, none
      met criteria for primary progressive aphasia. These subjects with primary
      progressive apraxia of speech included eight females and four males, with a mean
      age of onset of 73 years (range: 49-82). There were no specific additional shared
      patterns of neurological or neuropsychological impairment in the subjects with
      primary progressive apraxia of speech, but there was individual variability. Some
      subjects, for example, had mild features of behavioural change, executive
      dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter
      revealed focal atrophy of superior lateral premotor cortex and supplementary
      motor area. Voxel-based morphometry of white matter showed volume loss in these
      same regions but with extension of loss involving the inferior premotor cortex
      and body of the corpus callosum. These same areas of white matter loss were
      observed with diffusion tensor imaging analysis, which also demonstrated reduced
      fractional anisotropy and increased mean diffusivity of the superior longitudinal
      fasciculus, particularly the premotor components. Statistical parametric mapping
      of the [(18)F]-fluorodeoxyglucose positron emission tomography scans revealed
      focal hypometabolism of superior lateral premotor cortex and supplementary motor
      area, although there was some variability across subjects noted with CortexID
      analysis. [(11)C]-Pittsburg compound B positron emission tomography binding was
      increased in only one of the 12 subjects, although it was unclear whether the
      increase was actually related to the primary progressive apraxia of speech. A
      syndrome characterized by progressive pure apraxia of speech clearly exists, with
      a neuroanatomic correlate of superior lateral premotor and supplementary motor
      atrophy, making this syndrome distinct from primary progressive aphasia.

PMID- 22382357
TI  - A novel congenital myasthenic syndrome due to decreased acetylcholine receptor
      ion-channel conductance.
AB  - Muscle acetylcholine receptor ion channels mediate neurotransmission by
      depolarizing the postsynaptic membrane at the neuromuscular junction. Inherited
      disorders of neuromuscular transmission, termed congenital myasthenic syndromes,
      are commonly caused by mutations in genes encoding the five subunits of the
      acetylcholine receptor that severely reduce endplate acetylcholine receptor
      numbers and/or cause kinetic abnormalities of acetylcholine receptor function. We
      tracked the cause of the myasthenic disorder in a female with onset of first
      symptoms at birth, who displayed mildly progressive bulbar, respiratory and
      generalized limb weakness with ptosis and ophthalmoplegia. Direct DNA sequencing
      revealed heteroallelic mutations in exon 8 of the acetylcholine receptor epsilon
      subunit gene. Two alleles were identified: one with the missense substitution
      p.epsilonP282R, and the second with a deletion, c.798_800delCTT, which result in
      the loss of a single amino acid, residue F266, within the M2 transmembrane
      domain. When these acetylcholine receptor mutations were expressed in HEK 293
      cells, the p.epsilonP282R mutation caused severely reduced expression on the cell
      surface, whereas p.epsilonDeltaF266 gave robust surface expression. Single
      channel analysis for p.epsilonDeltaF266 acetylcholine receptor channels showed
      the longest burst duration population was not different from wild-type
      acetylcholine receptor (4.39 +/- 0.6 ms versus 4.68 +/- 0.7 ms, n = 5 each) but
      that the amplitude of channel openings was reduced. Channel amplitudes at
      different holding potentials showed that single-channel conductance was
      significantly reduced in p.epsilonDeltaF266 acetylcholine receptor channels (42.7
      +/- 1.4 pS, n = 8, compared with 70.9 +/- 1.6 pS for wild-type, n = 6). Although
      a phenylalanine residue at this position within M2 is conserved throughout ligand
      gated excitatory cys-loop channel subunits, deletion of equivalent residues in
      the other subunits of muscle acetylcholine receptor did not have equivalent
      effects. Modelling the impact of p.epsilonDeltaF266 revealed only a minor
      alteration to channel structure. In this study we uncover the novel mechanism of
      reduced acetylcholine receptor channel conductance as an underlying cause of
      congenital myasthenic syndrome, with the 'low conductance' phenotype that results
      from the p.epsilonDeltaF266 deletion mutation revealed by the coinheritance of
      the low-expressor mutation p.epsilonP282R.

PMID- 22382358
TI  - Novel peripheral myelin protein 22 (PMP22) micromutations associated with
      variable phenotypes in Greek patients with Charcot-Marie-Tooth disease.

PMID- 22382360
TI  - The migraine theories of Liveing and Latham: a reappraisal.
AB  - This article discusses the leading 19th century British contributions to theories
      of migraine pathogenesis: Edward Liveing's theory of nerve storms and Peter
      Wallwork Latham's vasomotor theory, providing a detailed accounts of their
      origin, and their rise and fall in the latter decades of the century, emphasizing
      the central role of William Gowers in their ultimate downfall. The article
      concludes by discussing the reasons behind the rising reputation of Liveing's
      work, demonstrating how history may be made to serve contemporary ends.

PMID- 22382361
TI  - Intratumoral electroporation of IL-12 cDNA eradicates established melanomas by
      Trp2(180-188)-specific CD8+ CTLs in a perforin/granzyme-mediated and IFN-gamma
      dependent manner: application of Trp2(180-188) peptides.
AB  - Intratumoral electroporation (IT-EP) with IL-12 cDNA (IT-EP/IL12) can lead to the
      eradication of established B16 melanoma tumors in mice. Here, we explore the
      immunological mechanism of the antitumor effects generated by this therapy. The
      results show that IT-EP/IL12 applied only once resulted in eradication in 70%
      animals with large established B16 tumors. Tumor eradication required the
      participation of CD8+ T cells, but not CD4+ T cells and NK cells. IT-EP/IL12
      induced antigen-specific CD8+ T cell responses against the immunodominant
      Trp2(180-188) epitope and generated a systemic response, resulting in significant
      therapeutic effects against distal, untreated tumors. The therapeutic effect of
      IT-EP/IL12 was absent in perforin-deficient mice, indicating that tumor
      elimination occurred through conventional perforin/granzyme lysis by CTLs.
      Moreover, this therapy induced some degree of immunological memory that protected
      approximately one-third of the cured mice against a subsequent tumor challenge.
      Moreover, antitumor efficacy and long-term protection against B16 were
      significantly improved by concurrent Trp2 peptide immunization through more
      induction of Ag-specific CTL responses and more attraction of IFN-gamma
      expressing CD8+ T cells into tumor sites. The antitumor effect of IT-EP/IL12
      required the participation of IFN-gamma, which was shown to induce MHC class I
      expression on B16 cells and increase the lytic activity of the CD8+ CTL generated
      by IT-EP/IL12. The results from these animal studies may help in the development
      of IT-EP/IL12 for cancer patients.

PMID- 22382362
TI  - Assessment of association between BRAF-V600E mutation status in melanomas and
      clinical response to ipilimumab.
AB  - Ipilimumab, a fully human monoclonal antibody against cytotoxic T lymphocyte
      antigen-4, has demonstrated significant improvement in overall survival in
      previously treated advanced melanoma patients. The BRAF inhibitor, vemurafenib,
      has shown up to 78% objective response rates in melanoma patients harboring the
      BRAF-V600E mutation but not in patients lacking the mutation. As an immune
      potentiator, the mechanism of action of ipilimumab may not be dependent of the
      activity of the BRAF pathway. To test this, we investigated whether the clinical
      activity of ipilimumab would be affected by the BRAF-V600E mutation status of the
      tumors. Thus, this retrospective analysis was carried using a set of tumor
      biopsies from a completed phase II clinical trial. CA184004 was a randomized,
      double-blind, multicenter trial of 82 previously treated or untreated patients
      with unresectable stage III/IV melanoma. Patients received ipilimumab 3 or 10
      mg/kg every 3 weeks for four doses followed by maintenance dosing in eligible
      patients. The BRAF-V600E mutation status for 80 patients was determined in tumor
      biopsies by PCR-based assays. Data on disease control were available for 69
      patients with evaluated BRAF-V600E mutation status. Rates of objective responses
      and stable disease in patients with BRAF-V600E mutation positive tumors (30%)
      were comparable to those in patients with the wild-type gene (~33%). Eleven
      patients displayed Durable Disease Control (DDC) of which 55% had BRAF-V600E
      mutation positive tumors and 45% did not. In the 48 patients showing no DDC, the
      mutation frequency was 50%. In this study, no association between BRAF-V600E
      mutation status of melanoma tumors and DDC after treatment with ipilimumab was
      detected.

PMID- 22382359
TI  - Cerebral causes and consequences of parkinsonian resting tremor: a tale of two
      circuits?
AB  - Tremor in Parkinson's disease has several mysterious features. Clinically, tremor
      is seen in only three out of four patients with Parkinson's disease, and tremor
      dominant patients generally follow a more benign disease course than non-tremor
      patients. Pathophysiologically, tremor is linked to altered activity in not one,
      but two distinct circuits: the basal ganglia, which are primarily affected by
      dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical
      circuit, which is also involved in many other tremors. The purpose of this review
      is to integrate these clinical and pathophysiological features of tremor in
      Parkinson's disease. We first describe clinical and pathological differences
      between tremor-dominant and non-tremor Parkinson's disease subtypes, and then
      summarize recent studies on the pathophysiology of tremor. We also discuss a
      newly proposed 'dimmer-switch model' that explains tremor as resulting from the
      combined actions of two circuits: the basal ganglia that trigger tremor episodes
      and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we
      address several important open questions: why resting tremor stops during
      voluntary movements, why it has a variable response to dopaminergic treatment,
      why it indicates a benign Parkinson's disease subtype and why its expression
      decreases with disease progression.

PMID- 22382363
TI  - Ordered bimetallic coordination networks featuring rare earth and silver cations.
AB  - Three lanthanide complexes of the ditopic ligand 3-cyanopentane-2,4-dionate
      (acacCN) have been synthesized and structurally characterized. Longer
      intermolecular contacts result in ninefold coordination of the cation in
      Ce(acacCN)(3)(H(2)O)(2), whereas mononuclear complexes of the same stoichiometry
      with coordination number eight are obtained for the smaller Eu(III) and Yb(III)
      cations. Reaction of these labile compounds with AgPF(6) leads to re-organization
      of the coordination sphere of the rare earth cations: neutral extended structures
      are formed in which the peripheric -CN moieties of Ln(acacCN)(4) anions
      coordinate to silver cations. The initially formed heterometallic networks show
      additional coordination of water or inclusion of solvent molecules; three
      different structure types, two of them as isomorphous pairs, have been
      characterized. In the case of Eu(III) and Yb(III), these solids are instable when
      stored in their mother liquor and undergo a slow aging process, finally resulting
      in phase pure stable and solvent-free 3D networks Ln(acacCN)(4)Ag.

PMID- 22382364
TI  - Linking genetics with biology in disease research: an interview with Nick Hastie.

PMID- 22382365
TI  - Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance
      to human disease.
AB  - Iron-sulfur (Fe-S) clusters are ubiquitous cofactors composed of iron and
      inorganic sulfur. They are required for the function of proteins involved in a
      wide range of activities, including electron transport in respiratory chain
      complexes, regulatory sensing, photosynthesis and DNA repair. The proteins
      involved in the biogenesis of Fe-S clusters are evolutionarily conserved from
      bacteria to humans, and many insights into the process of Fe-S cluster biogenesis
      have come from studies of model organisms, including bacteria, fungi and plants.
      It is now clear that several rare and seemingly dissimilar human diseases are
      attributable to defects in the basic process of Fe-S cluster biogenesis. Although
      these diseases -which include Friedreich's ataxia (FRDA), ISCU myopathy, a rare
      form of sideroblastic anemia, an encephalomyopathy caused by dysfunction of
      respiratory chain complex I and multiple mitochondrial dysfunctions syndrome -
      affect different tissues, a feature common to many of them is that mitochondrial
      iron overload develops as a secondary consequence of a defect in Fe-S cluster
      biogenesis. This Commentary outlines the basic steps of Fe-S cluster biogenesis
      as they have been defined in model organisms. In addition, it draws attention to
      refinements of the process that might be specific to the subcellular
      compartmentalization of Fe-S cluster biogenesis proteins in some eukaryotes,
      including mammals. Finally, it outlines several important unresolved questions in
      the field that, once addressed, should offer important clues into how
      mitochondrial iron homeostasis is regulated, and how dysfunction in Fe-S cluster
      biogenesis can contribute to disease.

PMID- 22382368
TI  - The role of CPK isoenzymes in predicting extrauterine early pregnancy.
AB  - OBJECTIVE: To evaluate the ability of Creatine phosphokinase (CPK) levels and CPK
      MB proportion to differentiate between extra and intrauterine of very early
      gestations with unknown location. MATERIALS AND METHODS: The study is case
      control. CPK levels and CPK-MB proportion in 51 women with extrauterine
      pregnancies were compared to those in 28 women with early intrauterine
      pregnancies. RESULTS: No significant difference was found between women with
      extrauterine pregnancies and early intrauterine pregnancies in the levels of CPK
      (80.9 +/- 62.1 vs. 74.9 +/- 51.5; p = 0.66) and CPK-MB proportion (16.2 +/- 10.1%
      vs. 15.1 +/- 11.1%; p = 0.86). CONCLUSION: CPK and CPK-MB proportion
      determinations do not contribute to the clinical differentiation between early
      intra and extrauterine pregnancies.

PMID- 22382366
TI  - Understanding the genetic and molecular pathogenesis of Friedreich's ataxia
      through animal and cellular models.
AB  - In 1996, a link was identified between Friedreich's ataxia (FRDA), the most
      common inherited ataxia in men, and alterations in the gene encoding frataxin
      (FXN). Initial studies revealed that the disease is caused by a unique, most
      frequently biallelic, expansion of the GAA sequence in intron 1 of FXN. Since the
      identification of this link, there has been tremendous progress in understanding
      frataxin function and the mechanism of FRDA pathology, as well as in developing
      diagnostics and therapeutic approaches for the disease. These advances were the
      subject of the 4th International Friedreich's Ataxia Conference held on 5th-7th
      May in the Institut de Genetique et de Biologie Moleculaire et Cellulaire,
      Illkirch, France. More than 200 scientists gathered from all over the world to
      present the results of research spanning all areas of investigation into FRDA
      (including clinical aspects, FRDA pathogenesis, genetics and epigenetics of the
      disease, development of new models of FRDA, and drug discovery). This review
      provides an update on the understanding of frataxin function, developments of
      animal and cellular models of the disease, and recent advances in trying to
      uncover potential molecules for therapy.

PMID- 22382369
TI  - Mullerian adenosarcoma of the uterus with heterologous elements: two case reports
      and literature review.

PMID- 22382370
TI  - Preeclampsia and depression: a case-control study in Tehran.
AB  - PURPOSE: This study was conducted to determine the correlation between
      preeclampsia and depression. METHODS: Participants in this study included 156
      cases with preeclampsia and 156 controls without any history of preeclampsia who
      were all newly admitted to antepartum wards, emergency room wards, and labor and
      delivery wards of the study hospitals (Valieasr, Shariatti, Mirza Koochak Khan,
      Shahid Akbar Abadi, Baharloo and Arash). They consented and completed a
      questionnaire on demographic characteristics, obstetric, delivery and infant
      information and Patient Health Questionnaire (PHQ-9) to assess their depression
      status. Data were analyzed through independent t test, Mann-Whitney U test, Chi
      squared test, Fisher's exact test and multiple regression by SPSS and STATA.
      RESULTS: Moderate to severe depression was found in 31.2% of the cases and 24.8%
      of the controls. Women with no depression in comparison with women with mild
      depression had a 1.81-fold (95% CI 1.05-3.14; P = 0.03) increased risk of
      preeclampsia, while moderate to severe depression correlated with a 2.52-fold
      increase (95% CI 1.05-6.02; P = 0.03) after adjustment of the probable
      confounding variables. DISCUSSION: With regard to the high prevalence of moderate
      to severe depression and its association with preeclampsia, our findings support
      and suggest efforts for screening depression among pregnant women and appropriate
      educational studies for mental and psychological problems during pregnancy.

PMID- 22382371
TI  - Spinal versus general anesthesia in cesarean sections: the effects on
      postoperative pain perception.
AB  - OBJECTIVE: To compare postoperative pain perception and analgesia requirements in
      patients undergoing cesarean section (CS) using general versus spinal anesthesia.
      STUDY DESIGN: A prospective, observational study of patients undergoing elective
      CS during 2009 under either general or spinal anesthesia. Postoperative pain
      intensity and analgesia requirements were evaluated for up to 48 h after surgery.
      RESULTS: A total of 153 women were enrolled; 77 received general and 76 received
      regional anesthesia. Postoperative meperidine requirements in the first 24 h were
      significantly higher in the general anesthesia group. Pain scores were mostly
      comparable between the groups. Nevertheless, lower pain scores were graded after
      8 h in the general versus the spinal anesthesia and this reversed at 48 h.
      CONCLUSION: Spinal anesthesia is comparable to general anesthesia in terms of
      post-operative pain control. In choosing the type of anesthesia in CS, other
      factors such as the urgency and potential maternal and fetal hazards should be
      taken into account.

PMID- 22382372
TI  - The use of porcine acellular dermal matrix in silicone implant-based breast
      reconstruction.
AB  - INTRODUCTION: The most frequently occurring long-term complication in implant
      based breast reconstruction is fibrotic capsule formation at the recipient site,
      with concurrent dysesthesia and poor aesthetic results. Using porcine acellular
      dermal matrix (PADM) as a connective tissue graft material is supposed to improve
      the quality and quantity of soft tissue in implant-based breast reconstruction.
      This study investigates the indications for and the results and the costs of
      using PADM for the correction or prevention of implant-associated breast
      deformities. MATERIALS AND METHODS: This study reviewed a single surgeon's
      experience in the correction or prevention of implant-associated breast
      deformities with PADM in breast cancer-related breast reconstruction from 2009 to
      2011. A total of 23 patients (27 breasts) were included in the study. The
      aesthetic outcome, the incidence and the type of complication were analysed.
      Twenty-three women underwent breast cancer-related breast reconstruction: 19
      women underwent single-breast reconstruction and four women underwent bilateral
      reconstruction. RESULTS: Of the 23 patients who underwent breast reconstruction,
      18 (78%) were "satisfied" with the aesthetic and haptic outcome after implant
      based reconstruction with PADM. One patient (one breast) required another breast
      operation because of ipsilateral breast cancer recurrence during the follow-up
      period. PADM-assisted implant-based breast reconstruction has a satisfactory
      safety profile. CONCLUSION: The use of PADM as an interface matrix for implant
      based breast reconstruction yielded predictable and acceptable aesthetic and
      haptic results by preventing capsular contracture, rippling, implant malposition,
      soft-tissue thinning and failure of the silicone implant-based breast
      augmentation.

PMID- 22382373
TI  - The eyes have it.

PMID- 22382374
TI  - Necessity of routine ipsilateral hemithyroidectomy during laryngopharyngectomy
      for pyriform sinus cancer.
AB  - PURPOSE: The aim of this study was to revisit the role of hemithyroidectomy in
      the treatment of pyriform sinus cancer by determining the incidence of thyroid
      gland invasion by the tumor. MATERIALS AND METHODS: Medical records of 27
      patients with pyriform sinus cancer who underwent laryngopharyngectomy with
      ipsilateral hemithyroidectomy from 1999 to 2010 at a National Cancer Institute
      designated comprehensive cancer center were retrospectively reviewed. Computed
      tomographic scans of the neck, operative notes, and surgical specimens were
      examined to determine the presence of thyroid gland invasion by imaging, clinical
      appearance, and pathology. RESULTS: There were 19 male and 8 female patients (age
      range, 44-79 years; mean, 59.9 years). Most of the cases (85%) had advanced-stage
      disease. Extralaryngeal spread of tumor with thyroid cartilage invasion was noted
      in the computed tomographic scans of 5 patients; however, there was no radiologic
      evidence of thyroid gland invasion in any patient. No gross thyroid gland
      invasion by the tumor was appreciated in any patient during surgery. No
      histologic evidence of tumoral invasion of the thyroid gland was found in any of
      27 surgical specimens. CONCLUSIONS: Results of this study suggest that thyroid
      gland invasion by pyriform sinus cancer is not common. Therefore, a routine
      ipsilateral hemithyroidectomy may not be necessary in the treatment of every
      patient with pyriform sinus cancer, unless there is evidence of thyroid gland
      invasion.

PMID- 22382375
TI  - [Measuring the subjective visual vertical using a portable system: a comparison
      with the standard darkroom method].
AB  - OBJECTIVE: Assessing otolithic functions in the case of vertigo, although
      significant, is challenging from a practical point of view. A tilt of the
      subjective visual vertical (SVV) is a very sensitive sign of vestibular tonus
      imbalance in the roll plane. The standard method, a light bar in the dark,
      requires expensive, stationary equipment. However, portable equipment has been
      developed. The patient, who is in complete darkness afforded by a cover, sits in
      front of a monitor that can be seen by him and the examiner. Results obtained
      with this system were validated and compared with the standard application.
      PATIENTS AND METHODS: Measurements were taken in 100 unselected, consecutive
      patients suffering from dizziness treated at the Baumrain Klinik, Bad Berleburg
      as well as in 26 healthy volunteers. All were examined and diagnosed by an ENT
      physician. Measurements in all participants were taken first with the standard
      procedure (equipment Vertitest) followed by the portable procedure (Vertistar
      equipment). In each case the deviation of the absolute from the true vertical was
      measured and the mean differences between the two procedures calculated. These
      were then analyzed using a paired t-test with the help of the SPSS system.
      RESULTS: Comparative measurements in the dizziness group (n = 100), t(25) =
      0.868, p = 0.394 and in the healthy control group (n = 26), t(99) = -0.192, p =
      0.848 showed no significant differences in the distribution of SVV values while
      using the stationary or the portable version. Inter-test reliability was
      significantly positive (r = 0.852; p < 0.01, n = 126). CONCLUSIONS: The portable
      method for measuring SVV is practical, flexible and cost-effective and
      demonstrates the same diagnostic accuracy as the stationary method.

PMID- 22382376
TI  - Comment on "Maternal and fetal exposure to pesticides associated to genetically
      modified foods in Eastern Townships of Quebec, Canada" by A. Aris and S. Leblanc
      [Reprod. Toxicol. 31 (2011) 528-533].

PMID- 22382378
TI  - The impact of enhanced atmospheric carbon dioxide on yield, proximate
      composition, elemental concentration, fatty acid and vitamin C contents of tomato
      (Lycopersicon esculentum).
AB  - The global average temperature has witnessed a steady increase during the second
      half of the twentieth century and the trend is continuing. Carbon dioxide, a
      major green house gas is piling up in the atmosphere and besides causing global
      warming, is expected to alter the physico-chemical composition of plants. The
      objective of this work was to evaluate the hypothesis that increased CO(2) in the
      air is causing undesirable changes in the nutritional composition of tomato
      fruits. Two varieties of tomato (Lycopersicon esculentum) were grown in ambient
      (400 MUmol mol(-1)) and elevated (1,000 MUmol mol(-1)) concentration of CO(2)
      under controlled conditions. The fruits were harvested at premature and fully
      matured stages and analyzed for yield, proximate composition, elemental
      concentration, fatty acid, and vitamin C contents. The amount of carbohydrates
      increased significantly under the enhanced CO(2) conditions. The amount of crude
      protein and vitamin C, two important nutritional parameters, decreased
      substantially. Fatty acid content showed a mild decrease with a slight increase
      in crude fiber. Understandably, the effect of enhanced atmospheric CO(2) was more
      pronounced at the fully matured stage. Mineral contents of the fruit samples
      changed in an irregular fashion. Tomato fruit has been traditionally a source of
      vitamin C, under the experimental conditions, a negative impact of enhanced CO(2)
      on this source of vitamin C was observed. The nutritional quality of both
      varieties of tomato has altered under the CO(2) enriched atmosphere.

PMID- 22382377
TI  - Molecular alterations underlying the enhanced disruption of spermatogenesis by
      2,5-hexanedione and carbendazim co-exposure.
AB  - The current study investigated the co-exposure effects of 2,5-hexanedione (HD)
      and carbendazim (CBZ) on gene expression underlying the enhanced pathology
      previously observed. Adult male rats were exposed to HD (0.33 or 1%) followed by
      CBZ (67 or 200 mg/kg), and testis samples were collected after 3 and 24 h.
      Microarray analysis at 3 h revealed that CBZ and HD interact in an agonistic, or
      synergistic, way at the gene level. Further analysis of candidate genes by qRT
      PCR at both 3 and 24 h after co-exposure, revealed that Loxl1 and Clca2/Clca4l
      were both decreased in expression. Immunohistochemical analysis of Loxl1 at 24 h
      revealed that Loxl1 is localized to the seminiferous tubules, with the most
      intense staining in the basement membrane, blood vessels, and acrosomes, with the
      relative intensity reflecting the gene level changes at 3 h. These findings
      provide candidate genes for further investigation of the testicular response to
      damage.

PMID- 22382379
TI  - Emissions of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs),
      and dioxin-like polychlorinated biphenyls (PCBs) to air from waste incinerators
      and high thermal processes in India.
AB  - This study investigated dioxins and dioxin-like polychlorinated biphenyls in
      gasses emitted from waste incinerators and thermal processes in central and
      western parts of India. The concentrations of polychlorinated dibenzo-p-dioxins
      and dibenzofurans (PCDDs/DFs) ranged from 0.0070 to 26.8140 ng toxicity
      equivalent (TEQ)/Nm(3), and those of dioxin-like polychlorinated biphenyls (PCBs)
      ranged from 0.0001 * 10(-1) to 0.0295 ng TEQ/Nm(3). The characteristics of mean
      PCDD/F I-TEQ concentration and congener profiles were studied over all the
      samples of air. In particular, a pattern consisting of a low proportion of dioxin
      like PCBs and high proportion of PCDDs/DFs was common for all the samples from
      incinerators and high-temperature processes.

PMID- 22382380
TI  - Attitudes to bystander cardiopulmonary resuscitation in Japan in 2010.
AB  - BACKGROUND: Early initiation of bystander cardiopulmonary resuscitation (CPR)
      improves the chances of successful resuscitation and survival. The aim of the
      present study was to identify the attitudes of Japanese subjects toward bystander
      CPR and to compare them with those observed in previous studies in 1998 and 2006.
      METHODS AND RESULTS: Participants were asked about their willingness to perform
      CPR in 5 different scenarios and their willingness to perform chest compression
      (CC) plus mouth-to-mouth ventilation (MMV) versus CC alone. A total of 2,785
      individuals completed the questionnaire, including high school students,
      teachers, medical nurses, and medical students, whose characteristics were not
      statistically different from those in the previous studies. Only 15-30% of
      participants were likely to perform CC plus MMV, especially on a stranger or a
      trauma victim; these percentages in nurses and medical students were
      significantly lower than those in the previous studies. But 50-100% of them were
      likely to perform CC alone, consistent with the results obtained in 2006. The
      reasons for the unwillingness among laypeople to perform CC plus MMV were
      inadequate knowledge and/or doubt regarding whether they could perform the
      techniques effectively, while health-care providers reported a fear of disease
      transmission. CONCLUSIONS: Most participants are unlikely to perform CC plus MMV,
      especially on a stranger or trauma victim, but are more likely to perform CC
      alone, as also found in the previous studies.

PMID- 22382381
TI  - Urotensin II stimulates vascular endothelial growth factor secretion from
      adventitial fibroblasts in synergy with angiotensin II.
AB  - BACKGROUND: The adventitia plays an important role in and is considered to be the
      initiating site for vascular remodeling. Urotensin II (UII) and angiotensin II
      (Ang II) are the two most important vascular peptides involved in vascular
      remodeling in the adventitia. Nevertheless, little is known about their effect on
      the expression of vascular endothelial growth factor (VEGF). It was hypothesized
      that both UII and Ang II could induce VEGF expression in adventitial fibroblasts
      and VEGF may play a role in cell proliferation and collagen I synthesis induced
      by UII or Ang II. METHODS AND RESULTS: Growth-arrested adventitial fibroblasts
      were incubated in serum-free medium with UII and/or Ang II and inhibitors of the
      mitogen-activated protein kinase (MAPK) pathway or VEGF-neutralizing antibodies.
      The VEGF expression was evaluated using enzyme-linked immunosorbent assay
      (ELISA), while the proliferation and collagen I synthesis were detected using
      methyl thiazol tetrazolium (MTT) assay and ELISA. It was found that: (1) both UII
      and Ang II could stimulate VEGF expression in adventitial fibroblasts and they
      had a synergistic effect; (2) MAPK pathway inhibitors could inhibit VEGF
      secretion induced by UII and/or Ang II; and (3) VEGF-neutralizing antibodies
      could inhibit UII/Ang II-induced cell proliferation and collagen synthesis in
      adventitial fibroblasts. CONCLUSIONS: Induction of VEGF expression may be a new
      mechanism involved in vascular remodeling for UII and Ang II.

PMID- 22382382
TI  - Impact of positive peri-stent vascular remodeling after sirolimus-eluting and
      paclitaxel-eluting stent implantation on 5-year clinical outcomes: intravascular
      ultrasound analysis from the Poststent Optimal Stent Expansion Trial multicenter
      randomized trial.
AB  - BACKGROUND: Positive peri-stent vascular remodeling (PPVR) after drug-eluting
      stent (DES) implantation is an important mechanism of late-acquired stent
      malapposition (LASM). METHODS AND RESULTS: A total of 226 patients (sirolimus
      eluting stent [SES], n=105; paclitaxel-eluting stent [PES], n=121) from the
      Poststent Optimal Stent Expansion Trial who underwent a post-intervention and 9
      month follow-up intravascular ultrasound were followed clinically for 5 years.
      PPVR was arbitrarily defined as a >10% increase in the external elastic membrane
      volume index at follow-up. PPVR and LASM occurred more frequently with SESs than
      with PESs. The 5-year rate of major adverse cardiac events was lower with SES
      than with PES (10.7% vs. 23.2%, P=0.002). The late and very late stent thrombosis
      (ST) rate was similar between the 2 DES types, but it was higher in patients with
      PPVR than in those without PPVR (8.8% vs. 1.3%, P=0.009) regardless of the DES
      type. Early discontinuation (<1 year) of dual antiplatelet therapy (DAPT; hazard
      ratio [HR], 24.14; 95% confidence interval [CI]: 4.90-118.87; P<0.001), PPVR (HR,
      14.94; 95%CI: 1.85-120.46; P=0.011), LASM (HR, 8.01; 95%CI: 1.93-33.16; P=0.004),
      and stent length (HR, 1.14; 95%CI: 0.98-1.32 per mm; P=0.078) were associated
      with increased risk of late and very late ST. CONCLUSIONS: PPVR and LASM
      development after DES implantation, along with early discontinuation of DAPT and
      longer stent length, are important risk factors of late and very late ST.

PMID- 22382383
TI  - Effects of rosuvastatin and atorvastatin on renal function: meta-analysis.
AB  - BACKGROUND: Several clinical trials have reported inconsistent findings for the
      effects of rosuvastatin (RSV) and atorvastatin (ATV) on renal function. The aim
      of this meta-analysis was to investigate the effects of these 2 statins on
      glomerular filtration rate (GFR) and proteinuria respectively, and determine
      which is better. METHODS AND RESULTS: PubMed, CENTRAL, Web of Knowledge, and
      ClinicalTrials.gov website were searched for randomized controlled trials.
      Eligible studies reported GFR and/or proteinuria during treatment with RSV or ATV
      compared with control (placebo, no statins, or usual care), or RSV compared with
      ATV head to head. Trials that enrolled dialysis participants and teenagers were
      excluded. Statistical heterogeneity was assessed using the I(2) statistic, and
      pooled results using the random-effects model. The standardized mean differences
      (SMD) and ratio of means (ROM) were measured, respectively, to analyze GFR and
      proteinuria. Sixteen trials with a total number of 24,278 participants were
      identified. Compared with control, changes in the SMD of GFR were 0.04 (95%
      confidence interval [CI]: 0.01-0.07) and 0.59 (95%CI: 0.12-1.06) for RSV and ATV,
      respectively. The ROMs of proteinuria were 0.59 (95%CI: 0.46-0.74) for RSV vs.
      the control group, and 1.23 (95%CI: 1.05-1.43) in the head-to-head comparison.
      CONCLUSIONS: Both RSV and ATV improve GFR, and ATV seems to be more effective in
      reducing proteinuria. The validity and clinical significance require high-quality
      intensive studies with composite clinic endpoints of kidney and death.

PMID- 22382384
TI  - Evidence-based indicators of neuropsychological change in the individual patient:
      relevant concepts and methods.
AB  - Repeated assessments are a relatively common occurrence in clinical
      neuropsychology. The current paper will review some of the relevant concepts
      (e.g., reliability, practice effects, alternate forms) and methods (e.g.,
      reliable change index, standardized based regression) that are used in repeated
      neuropsychological evaluations. The focus will be on the understanding and
      application of these concepts and methods in the evaluation of the individual
      patient through examples. Finally, some future directions for assessing change
      will be described.

PMID- 22382387
TI  - Cognitive disturbances and neuropsychological changes after surgical treatment in
      a cohort of 185 patients with idiopathic normal pressure hydrocephalus.
AB  - Although idiopathic normal pressure hydrocephalus (iNPH) is considered a
      treatable dementia, there is still some controversy regarding the cognitive
      improvement in these patients. The main aims of this study were to analyze
      baseline cognitive status and to study the neuropsychological changes after
      surgical treatment in a sample of 185 consecutive iNPH patients. An additional
      aim was to identify the variables that influenced the cognitive outcome. Specific
      tests assessing memory, attention, visual scanning, executive functions (EFs),
      and motor speed were used before and 6 months after shunting. The cognitive
      domains most affected at baseline were memory, EFs, attention, and psychomotor
      speed. After shunting, significant differences in the group as a whole were found
      in all tests except Digits Forward and Trail Making Part B. However, less than
      50% of patients showed a significant improvement when analyzed individually.
      Previous global cognitive status assessed by Mini-Mental State Examination
      baseline scores was the best predictor for the cognitive outcome.

PMID- 22382386
TI  - Computerized neuropsychological assessment devices: joint position paper of the
      American Academy of Clinical Neuropsychology and the National Academy of
      Neuropsychology.
AB  - This joint position paper of the American Academy of Clinical Neuropsychology and
      the National Academy of Neuropsychology sets forth our position on appropriate
      standards and conventions for computerized neuropsychological assessment devices
      (CNADs). In this paper, we first define CNADs and distinguish them from examiner
      administered neuropsychological instruments. We then set forth position
      statements on eight key issues relevant to the development and use of CNADs in
      the healthcare setting. These statements address (a) device marketing and
      performance claims made by developers of CNADs; (b) issues involved in
      appropriate end-users for administration and interpretation of CNADs; (c)
      technical (hardware/software/firmware) issues; (d) privacy, data security,
      identity verification, and testing environment; (e) psychometric development
      issues, especially reliability, and validity; (f) cultural, experiential, and
      disability factors affecting examinee interaction with CNADs; (g) use of
      computerized testing and reporting services; and (h) the need for checks on
      response validity and effort in the CNAD environment. This paper is intended to
      provide guidance for test developers and users of CNADs that will promote
      accurate and appropriate use of computerized tests in a way that maximizes
      clinical utility and minimizes risks of misuse. The positions taken in this paper
      are put forth with an eye toward balancing the need to make validated CNADs
      accessible to otherwise underserved patients with the need to ensure that such
      tests are developed and utilized competently, appropriately, and with due concern
      for patient welfare and quality of care.

PMID- 22382388
TI  - Cilengitide in bevacizumab-refractory high-grade glioma:  two case reports and
      critical review of the literature.
AB  - High-grade gliomas (HGG) are aggressive and highly vascularized brain tumours.
      Despite multimodality therapy including surgery, radiation therapy and in many
      cases temozolomide chemotherapy, the prognosis is dismal. Salvage therapies
      following progression after radiation therapy and chemotherapy have historically
      yielded disappointing results. Bevacizumab is an interesting antiangiogenic drug
      used as a second-line treatment but although most patients benefit, essentially
      all patients ultimately progress. Moreover, some clinical studies have documented
      low activity of a second attempt at vascular endothelial growth factor pathway
      inhibition after failure of a first. The use of another drug with a different
      angiogenic pathway inhibition may probably result in a higher activity. Here, we
      describe, to our knowledge for the first time, the activity and safety of
      cilengitide, an agent with a different antiangiogenic and anti-invasive activity,
      administered in two bevacizumab-refractory patients with HGG. In addition, we
      present a rapid review of the activity of cilengitide in HGG.

PMID- 22382389
TI  - Inhibition of nuclear factor-kappaB by dehydroxymethylepoxyquinomicin induces
      schedule-dependent chemosensitivity to anticancer drugs and enhances chemoinduced
      apoptosis in osteosarcoma cells.
AB  - Osteosarcoma (OS) is the most common primary malignant bone tumor, usually
      developing in children and adolescents, and is highly invasive and metastatic,
      potentially developing chemoresistance. Thus, novel effective treatment regimens
      are urgently needed. This study was the first to investigate the anticancer
      effects of dehydroxymethylepoxyquinomicin (DHMEQ), a highly specific nuclear
      factor-kappaB (NF-kappaB) inhibitor, on the OS cell lines HOS and MG-63. We
      demonstrate that NF-kappaB blockade by DHMEQ inhibits proliferation, decreases
      the mitotic index, and triggers apoptosis of OS cells. We examined the effects of
      combination treatment with DHMEQ and cisplatin, doxorubicin, or methotrexate,
      drugs commonly used in OS treatment. Using the median effect method of Chou and
      Talalay, we evaluated the combination indices for simultaneous and sequential
      treatment schedules. In all cases, combination with a chemotherapeutic drug
      produced a synergistic effect, even at low single-agent cytotoxic levels. When
      cells were treated with DHMEQ and cisplatin, a more synergistic effect was
      obtained using simultaneous treatment. For the doxorubicin and methotrexate
      combination, a more synergistic effect was achieved with sequential treatment
      using DHMEQ before chemotherapy. These synergistic effects were accompanied by
      enhancement of chemoinduced apoptosis. Interestingly, the highest apoptotic
      effect was reached with sequential exposure in both cell lines, independent of
      the chemotherapeutic agent used. Likewise, DHMEQ decreased cell invasion and
      migration, crucial steps for tumor progression. Our data suggest that combining
      DHMEQ with chemotherapeutic drugs might be useful for planning new therapeutic
      strategies for OS treatment, mainly in resistant and metastatic cases.

PMID- 22382390
TI  - Musculoskeletal tissue engineering by endogenous stem/progenitor cells.
AB  - From its inception, tissue engineering has had three tenets: cells, biomaterial
      scaffolds and signaling molecules. Among the triad, cells are the center piece,
      because cells are the building blocks of tissues. For decades, cell therapies
      have focused on the procurement, manipulation and delivery of healthy cells for
      the treatment of diseases or trauma. Given the complexity and potential high cost
      of cell delivery, there is recent and surging interest to orchestrate endogenous
      cells for tissue regeneration. Biomaterial scaffolds are vital for many but not
      all, tissue-engineering applications and serve to accommodate or promote multiple
      cellular functions. Signaling molecules can be produced by transplanted cells or
      endogenous cells, or delivered specifically to regulate cell functions. This
      review highlights recent work in tissue engineering and cell therapies, with a
      focus on harnessing the capacity of endogenous cells as an alternative or
      adjunctive approach for tissue regeneration.

PMID- 22382392
TI  - BMPRIB and BMPRII mRNA expression levels in goat ovarian follicles and the in
      vitro effects of BMP-15 on preantral follicle development.
AB  - This study evaluated the levels of bone morphogenetic protein receptors BMPRIB
      and BMPRII mRNA in goat follicles and the effects of bone morphogenetic protein
      15 (BMP-15) on the in vitro development of cultured preantral follicles. Real
      time polymerase chain reaction (PCR) was used to analyze the levels of BMPRIB and
      BMPRII mRNA in caprine preantral follicles and in small and large antral
      follicles. Preantral follicles (>=150 MUm) were also isolated from goat ovaries
      and cultured for 18 days in alpha-MEM(+) supplemented with or without BMP-15 (10,
      50, or 100 ng/ml). At the end of culture, some follicles were fixed for
      ultrastructural evaluation. Real-time PCR showed a reduction in BMPRII mRNA
      levels from the primary to secondary follicles. Higher levels of BMPRIB mRNA were
      observed in granulosa/theca cells from large antral follicles compared with small
      antral follicles. Moreover, BMPRII mRNA was expressed to a greater extent in
      cumulus-oocyte complexes from large antral follicles than in their respective
      granulosa/theca cells. In culture, 50 ng/ml BMP-15 positively influenced antral
      cavity formation and follicle growth after 18 days and also maintained follicular
      integrity. Thus, BMPRIB and BMPRII mRNAs are present in all follicular
      categories. BMP-15 (50 ng/ml) stimulates growth, antrum formation and the
      ultrastructural integrity of isolated caprine preantral follicles after 18 days
      of culture.

PMID- 22382393
TI  - A theoretical investigation of the relative stability of hydrated glycine and
      methylcarbamic acid--from water clusters to interstellar ices.
AB  - We have theoretically investigated how the low-energy conformers of the neutral
      and the zwitterionic forms of glycine as well as methylcarbamic acid are
      stabilized by the presence water. The MP2/6-311++G(d,p) method was utilized to
      conduct calculations on glycine and methylcarbamic acid in both isolated clusters
      and in clusters embedded in the conductor-like polarizable continuum model (C
      PCM), where the clusters explicitly contain between one and ten water molecules.
      The neutral forms of glycine and methylcarbamic acid were found to have similar
      hydration energies, whereas the neutral methylcarbamic acid was determined to be
      approximately 32 kJ mol(-1) more stable than the neutral glycine in the isolated
      clusters and 30 kJ mol(-1) more stable in the C-PCM embedded clusters. Both the
      number and strength of the hydrogen bonding interactions between water and the
      zwitterions drive the stability. This lowers the relative energy of the glycine
      zwitterion from 50 kJ mol(-1) above neutral glycine, when there are two water
      molecules in the clusters to 11 kJ mol(-1) below for the clusters containing ten
      water molecules. For the methylcarbamic acid clusters with two water molecules,
      the zwitterion is 51 kJ mol(-1) higher in energy than the neutral form, but it
      remains 13 kJ mol(-1) above the neutral methylcarbamic acid in the clusters
      containing ten water molecules. When the bulk water environment is simulated by
      the C-PCM calculations, we find both the methylcarbamic acid and glycine
      zwitterionic forms have similar energies at 20 kJ mol(-1) above the neutral
      methylcarbamic acid energy and 10 kJ mol(-1) lower than the neutral glycine
      energy. Although neither methylcarbamic acid nor glycine have been detected in
      the interstellar medium yet, our findings indicate that methylcarbamic acid is
      the more stable product from methylamine and carbon dioxide reactions in a water
      ice. This suggests that methylcarbamic acid likely plays a role in the
      intermediate steps if glycine is formed in the interstellar medium.

PMID- 22382391
TI  - Interaction of the conceptus and endometrium to establish pregnancy in mammals:
      role of interleukin 1beta.
AB  - Implantation and the establishment of pregnancy in mammals involves an intricate
      interplay of hormones, cytokines, growth factors, proteins, lipids, ions and the
      extracellular matrix between the uterine epithelium, stroma, immune cells and the
      conceptus trophectoderm. The divergent nature of implantation in the mouse, human
      and pig provides not only an interesting contrast in the establishment of
      pregnancy and early embryonic development but also intriguing similarities with
      regard to early endometrial-conceptus signaling. An interesting pro-inflammatory
      cytokine expressed in a number of mammalian species during the period of
      implantation is interleukin-1beta (IL1B). The presence of IL1B might be involved
      with immunotolerance at the maternal-placental interface and has been proposed as
      one of the mediators in placental viviparity. The production of IL1B and other
      proinflammatory cytokines might play a role in establishing pregnancy through
      modulation of the nuclear factor kappa-B (NFKB) system in a number of species. A
      model for the regulation of cellular progesterone receptor expression and NFKB
      activation for endometrial receptivity and conceptus attachment is continuing to
      evolve and is discussed in the present review.

PMID- 22382394
TI  - Total hip replacement in developmental dysplasia using an oval-shaped cementless
      press-fit cup.
AB  - PURPOSE: Acetabular roof deficiency due to subluxation of the femoral head
      (Hartofilakidis type II) increases the complexity of total hip arthroplasty. In
      these cases some form of support is usually required, to reach stable fixation of
      the acetabular component. Pursuing this aim, the oval-shaped cementless cranial
      socket could be an alternative to conventional treatment options. METHODS:
      Between 1998 and 2008, 37 patients (40 hips) underwent primary total hip
      arthroplasty using the cranial socket (mean follow-up 5.6 years, range 26 to 133
      months). In a retrospective study we compared these clinical and radiological
      results with the results of a matched control group consisting of 35 patients (40
      hips) treated with a standard cementless hemispherical cup in combination with
      bulk femoral autografting (mean follow-up 6.9 years, range 30 to 151 months).
      RESULTS: There were no statistically significant differences in the HHS (p=0.205)
      or the SF-36 (p=0.26) between both groups. There was no prosthesis failure due to
      septic or aseptic loosening. Time of surgery was significantly shorter in the
      cranial socket group (p<0.001). The acetabular component could be placed in the
      ideal rotational hip centre in 24 (60%) hips in the cranial socket group and 32
      (80%) hips in the control group, respectively. CONCLUSIONS: Our study indicates,
      that the cranial socket can be an alternative treatment option for the
      reconstruction of acetabular deficiency in osteoarthritis secondary to
      developmental dysplasia.

PMID- 22382395
TI  - Hydrotris(3-mesitylpyrazolyl)borato-copper(I) alkyne complexes: synthesis,
      structural characterization and rationalization of their activities as alkyne
      cyclopropenation catalysts.
AB  - The use of the bulky hydrotris(3-mesitylpyrazolyl)borate anionic ligand has
      allowed the synthesis of stable Tp(Ms)Cu(alkyne) complexes (alkyne = 1-hexyne, 1,
      phenylacetylene, 2, and ethyl propiolate, 3). The spectroscopic and structural
      features of these compounds and their relative reactivity have been examined,
      indicating the existence of a low pi back-bonding from the copper(I) centre to
      the alkyne. Ligand exchange experiments have shown that terminal alkyne adducts
      are more stable than internal alkyne analogues. In good accordance with this, the
      previously reported alkyne cyclopropenation reaction catalysed by the Tp(x)Cu
      complexes can be rationalized and correlated with their relative stability.

PMID- 22382396
TI  - Automated reminders decrease postoperative nausea and vomiting incidence in a
      general surgical population.
AB  - BACKGROUND: Guidelines to minimize the incidence of postoperative nausea and
      vomiting (PONV) have been implemented in many hospitals. In previous studies, we
      have demonstrated that guideline adherence is suboptimal and can be improved
      using decision support (DS). In this study, we investigate whether DS improves
      patient outcome through improving physician behaviour. METHODS: Medical
      information of surgical patients is routinely entered in our anaesthesia
      information management system (AIMS), which includes automated reminders for PONV
      management based on the simplified risk score by Apfel and colleagues. This study
      included consecutive adult patients undergoing general anaesthesia for elective
      non-cardiac surgery who were treated according to the normal clinical routine.
      The presence of PONV was recorded in the AIMS both during the recovery period and
      at 24 h. Two periods were studied: one without the use of DS (control period) and
      one with the use of DS (support period). DS consisted of reminders on PONV both
      in the preoperative screening clinic and at the time of anaesthesia. RESULTS: In
      the control period, 981 patients, of whom 378 (29%) were high-risk patients,
      received general anaesthesia. Overall, 264 (27%) patients experienced PONV within
      24 h. In the support period, 1681 patients, of whom 525 (32%) had a high risk for
      PONV, received general anaesthesia. In this period, only 378 (23%) patients
      experienced PONV within 24 h after operation. This difference is statistically
      significant (P=0.01). CONCLUSION: Automated reminders can improve patient outcome
      by improving guideline adherence.

PMID- 22382397
TI  - Vascularized fibular graft for bone defects after wide resection of
      musculoskeletal tumors.
AB  - BACKGROUND: In reconstruction by vascularized fibular graft (VFG) after wide
      resection of musculoskeletal tumors, there are problems such as the method of
      fixing the fibular graft, the period of achieving bone union, and the avoidance
      of postoperative fractures. We have performed VFG on 19 cases over a 30-year
      period. We have investigated these problems and now report the results. METHODS:
      From 1980 to 2009, we performed VFG on 19 cases to reconstruct the bone defect
      after resection of a musculoskeletal tumor. The mean age was 19.5 years.
      Reconstructed bone defects were located in the femur in 10 cases (1 of inlay
      graft, 1 of individual intercalary graft, 7 of intercalary graft into treated
      bone, 1 of curettaged bone marrow), the tibia in 3 cases (1 of individual
      intercalary graft, 2 of intercalary graft into treated bone), the humerus in 3
      cases (2 of sling procedure, 1 of individual intercalary graft), the foot in 2
      cases individual intercalary graft, and the sacroiliac joint in 1 case of
      individual intercalary graft. The mean follow-up period after surgery was 7.25
      years. We evaluated the success of primary bone union, the period required to
      achieve bone union, complications, clinical outcome, and the Musculoskeletal
      Tumor Society (MSTS) score. RESULTS: Successful bone union was achieved for 79%
      of cases (15/19 patients). The average period required to achieve bone union was
      7.8 months. There were 4 cases of non-union and 2 other complications. Clinical
      outcome status was continuous disease-free in 12 cases and died of disease in 7.
      The mean MSTS score was 98% (93-100%). CONCLUSION: Vascularized fibular graft is
      a useful reconstructive procedure for long-bone defects after wide excision of
      musculoskeletal tumors. The method of fixation can be selected according to the
      situation; although times required for bone union are long, it is possible to
      prevent postoperative fractures by a combined approach with treated bone and/or
      double barrel fibular grafts.

PMID- 22382398
TI  - Laryngoscopy findings and histological results in a rabbit gastroesophageal
      reflux model.
AB  - The role of lower esophageal sphincter (LES) in laryngopharyngeal reflux is
      controversial. In this study, we used an animal model to investigate the
      association between LES dysfunction and reflux laryngitis. Twelve healthy New
      Zealand albino rabbits (2.5-3.5 kg) were utilized in this study. The animals were
      divided into two groups. Eight rabbits underwent total cardiomyectomy to induce
      reflux, and the remaining four rabbits underwent a control sham operation. A
      laryngoscopy and a 24-hour intra-esophageal pH-metry were performed prior to
      surgery and again 2 and 8 weeks postsurgery. After the final laryngoscopy, all
      animals were sacrificed to obtain histological results. Total cardiomyectomy
      significantly increased the reflux index, the duration of the longest reflux
      episode and the total number of episodes that occurred in 24 h postsurgery. No
      significant difference was observed in the reflux finding score (RFS) between
      preoperative and 2-week postoperative rabbits (P = 0.11). But there was a
      statistically significant change in the RFS before and 8 weeks after the
      induction of reflux from 4.6 +/- 0.9 to 8.3 +/- 3.6 (P = 0.02). Submucous gland
      hyperplasia and inflammation were significantly increased in the reflux group
      compared to the control group. The results of this study suggest that chronic
      lower esophageal sphincter dysfunction is associated with reflux laryngitis in
      rabbits.

PMID- 22382399
TI  - Olfactory function following nasal surgery: a 1-year follow-up.
AB  - Olfactory dysfunction is a frequent symptom of nasal and sinunasal disease. Many
      of these patients undergo nasal sinus or nasal septum surgery. In this study, we
      evaluated the benefit of nasal surgery on olfactory function over a period of 12
      months. Patients included in this study underwent either nasal sinus or nasal
      septum surgery. All patients were tested for olfactory function using the
      "Sniffin' sticks" 16 item odor identification test. In addition, patients were
      asked to rate their nasal patency as well as their olfactory function at each
      visit. 157 patients were tested 3.5 months after surgery and 52 patients were
      tested again 12 months after surgery. Olfactory function improved significantly
      3.5 months after surgery in patients, who received nasal sinus surgery; no
      significant increase was found in patients treated with nasal septum surgery. At
      the 12-month follow-up, the increase in olfactory function over all patients just
      missed statistical significance. Individually, however, 19% of the patients
      exhibited improvement after 3.5 months and 17% after 12 months. These numbers
      increased in patients with rhinosinusitis with nasal polyps, who exhibited
      improvement of 30% after 3.5 months, and 32% after 12 months. Nasal sinus surgery
      produced an increase in measured olfactory function, but not nasal septum
      surgery. This increase appeared to be stable over the examined period of 12
      months.

PMID- 22382400
TI  - Increased percentage of T cells with the expression of CD127 and CD132 in
      hypertrophic adenoid in children with otitis media with effusion.
AB  - The hypertrophic adenoid may promote chronic suppurative otitis media in children
      as it fulfills its immune function. The number of lymphocytes in the adenoid and
      their cooperation in the immune response depend of on their proliferation and
      migration to the effector sites. Interleukin 7 (IL-7) is essential for the normal
      development and function lymphocytes. IL-7 plays pivotal role for activation and
      proliferation of T and B cells. The heterodimeric interleukin-7 receptor (IL-7R)
      is composed of the IL-7Ralpha (127) and the common cytokine receptor gammac
      (CD132). The aim of this study was to evaluate the percentage of lymphocytes T
      (CD4(+) and CD8(+)) with IL-7R (CD127 and CD132) expression in hypertrophic
      adenoid in children suffering with otitis media with effusion for a duration of 3
      months. Adenoid excised due to hypertrophy with or without chronic otitis media
      with effusion was used as study material. CD4(+) CD127(+), CD4(+)132(+),
      CD8(+)CD127(+) and CD8(+)CD132(+) cell subpopulations were identified using
      monoclonal antibodies and flow cytometry. The percentage of CD4(+) and CD8(+) T
      cells with CD127 receptor expression in hypertrophic adenoid of children with
      otitis media with effusion was statistically significantly higher than in
      hypertrophic adenoid group. The percentage of CD4(+) T cells with CD132
      expression in the study group was statistically significantly higher than in the
      reference group. The percentage of CD8(+) T cells with CD132(+) expression was
      not statistically different in both groups. The increased percentage of T
      lymphocytes with IL-7R expression (CD127 and CD132) in hypertrophic adenoid seems
      to influence the quantity of lymphocytes and upset the immunological function of
      tonsils which can influence the course of otitis media with effusion.

PMID- 22382401
TI  - BPA and PXR activation: human receptor is affected, mouse receptor is not.

PMID- 22382402
TI  - Effects of partial or total fish meal replacement by agricultural by-product
      diets on gonad maturation, sex steroids and vitellogenin dynamics of African
      catfish (Clarias gariepinus).
AB  - The establishment of the first sexual maturation was characterized in African
      catfish (Clarias gariepinus) in order to study the efficiency of replacement of
      fish meal (FM) by diets composed of local vegetable ingredients. Four diets were
      formulated containing decreasing levels of FM (50-0% for diet 1 to diet 4) and
      increasing proportions of vegetable ingredients (50-100%). Gonadosomatic index
      (GSI), diameter and percentages of developmental stages of oocytes, plasma sex
      steroids and vitellogenin dynamics were investigated from February to June using
      one-year-old fish. Fish were individually tagged, and 12 individuals from each
      diet were investigated monthly. Replacement of FM with plant ingredients did not
      affect the GSI neither in males, nor in females. All males were spermiating, and
      no abnormal gonads were found. In females, GSI and percentages of advanced stages
      of oocytes decreased during the dry season, indicating seasonal changes in gonad
      development. Moreover, oocytes were in late exogenous vitellogenesis, but no
      final maturation stages were observed, whatever the diet. Higher plasma levels of
      E2 in females and of androgens (T and 11-KT) in both sexes were observed in fish
      fed diet 4 than in those receiving diet 1 depending on the season. Levels of
      plasma E2 and ALP (indicator for vitellogenin) in males did not differ among
      treatments and seasons suggesting no phytoestrogenic activity. The results showed
      that total replacement of FM by vegetable diets composed of groundnut oilcakes,
      bean and sunflower meals has no deleterious effect on the onset of sexual
      maturation in African catfish but, may stimulate the sex steroid production and
      in turns may potentially exert some positive actions on reproductive success.

PMID- 22382403
TI  - Large- and small-size advantages in sneaking behaviour in the dusky frillgoby
      Bathygobius fuscus.
AB  - Sneaking tactic, a male alternative reproductive tactic involving sperm
      competition, is generally adopted by small individuals because of its
      inconspicuousness. However, large size has an advantage when competition occurs
      between sneakers for fertilization of eggs. Here, we suggest that both large- and
      small-size advantages of sneaker males are present within the same species. Large
      sneaker males of the dusky frillgoby Bathygobius fuscus showed a high success
      rate in intruding into spawning nests because of their advantage in competition
      among sneaker males in keeping a suitable position to sneak, whereas small
      sneakers had few chances to sneak. However, small sneaker males were able to stay
      in the nests longer than large sneaker males when they succeeded in sneak
      intrusion. This suggests the possibility of an increase in their paternity. The
      findings of these size-specific behavioural advantages may be important in
      considering the evolution of size-related reproductive traits.

PMID- 22382404
TI  - Spiders avoid sticking to their webs: clever leg movements, branched drip-tip
      setae, and anti-adhesive surfaces.
AB  - Orb-weaving spiders construct webs with adhesive silk but are not trapped by it.
      Previous studies have attributed this defense to an oily coating on their legs
      that protects against adhesion or, more recently, to behavioral avoidance of
      sticky lines. The old evidence is very weak, however, and the behavioral
      avoidance explanation is inadequate because orb-weavers push with their hind legs
      against sticky lines hundreds or thousands of times during construction of each
      orb and are not trapped. Video analyses of behavior and experimental observations
      of isolated legs pulling away from contact with sticky lines showed that the
      spider uses three anti-adhesion traits: dense arrays of branched setae on the
      legs that reduce the area of contact with adhesive material; careful engagement
      and withdrawal movements of its legs that minimize contact with the adhesive and
      that avoid pulling against the line itself; and a chemical coating or surface
      layer that reduces adhesion.

PMID- 22382406
TI  - Tau phosphorylation in human brain: relationship to behavioral disturbance in
      dementia.
AB  - Agitation and aggressive behavior are common symptoms of Alzheimer's disease
      (AD), and tangle density in frontal cortex is a possible regional substrate of
      these behaviors. To investigate this further, 16 AD patients, 8 patients with non
      AD dementia, and 13 age-matched control subjects for frontal cortex and,
      respectively, 21, 7, and 6 patients for parietal cortex were analyzed for tau and
      phospho-tau by enzyme-linked immunosorbent assay (ELISA). Agitation/aggression
      was determined by the Present Behavioural Examination. In a subset of cases,
      glycogen synthase kinase-3beta (GSK-3beta) phosphorylation and protein
      phosphatase 2A (PP2A) expression were measured. Phospho-tau and the phospho
      tau/total tau ratio were elevated in AD in both cortical regions. In keeping with
      our hypothesis, the phospho-tau/total tau ratio was elevated in the frontal
      cortex of those patients with agitation/aggression during life, and there was a
      significant correlation (p = 0.024) between these behaviors and the phospho
      tau/total tau ratio in the cortex. PP2A expression was lower (p < 0.01) in the
      frontal cortex of patients with high tau phosphorylation. This study confirms a
      link between tau phosphorylation and agitation/aggression and suggests that
      reducing tau phosphorylation may provide symptomatic relief.

PMID- 22382405
TI  - Cerebral microbleeds and age-related macular degeneration: the AGES-Reykjavik
      Study.
AB  - We test the hypothesis that cerebral microbleeds (CMB) and age-related macular
      degeneration (AMD), both linked to amyloid-beta deposition, are correlated. This
      study includes 4205 participants (mean age 76.2; 57.8% women) in the Age,
      Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). CMB were
      assessed from magnetic resonance images, and AMD was assessed using digital
      retinal images. Data were analyzed with multinomial logistic models controlling
      for major confounders. Evidence of CMB was detected in 476 persons (272 with
      strict lobar CMB and 204 with nonlobar CMB). AMD was detected in 1098 persons
      (869 with early AMD, 140 with exudative AMD, and 89 with pure geographic
      atrophy). Early and exudative AMD were not associated with CMB. The adjusted odds
      ratio of pure geographic atrophy was 1.62 (95% confidence interval 0.93-2.82, p =
      0.089) for having any CMB, 1.43 (0.66-3.06, p = 0.363) for strict lobar CMB, and
      1.85 (0.89-3.87, p = 0.100) for nonlobar CMB. This study provides no evidence
      that amyloid deposits in the brain and AMD are correlated. However, the
      suggestive association of geographic atrophy with CMB warrants further
      investigation.

PMID- 22382407
TI  - Development of palladium-catalyzed transformations using propargylic compounds.
AB  - It is known that propargylic compounds having an ester and a halide at the
      propargylic positions react with palladium complexes leading to pi
      propargylpalladium and allenylpalladium complexes, which cause various
      transformations in the presence of the reactants. The aim of the present study
      was to develop novel palladium-catalyzed transformations using propargylic
      compounds. As diastereoselective reactions of propargylic compounds with bis
      nucleophiles, we have developed palladium-catalyzed reactions of propargylic
      carbonates with 2-substituted cyclohexane-1,3-diones, 2-(2-hydroxyphenyl)acetates
      and 2-oxocyclohex-3-enecarboxylates. These processes produce highly substituted
      cyclic compounds in a highly stereoselective manner. Through our studies on the
      construction of substituted 2,3-allenols by the reactions of propargylic
      oxiranes, it has been made clear that palladium-catalyzed coupling reactions
      occur in the presence of arylboronic acids and terminal alkynes. The processes
      can be carried out in mild conditions to yield substituted 4-aryl-2,3-allenols in
      a diastereoselective manner. In our attempt to develop CO2-recycling reactions,
      we developed a methodology for the synthesis of cyclic carbonates by palladium
      catalyzed reactions of propargylic carbonates with phenols. Our findings
      suggested that the process proceeds through a pathway involving decarboxylation
      followed fixation of the liberated CO2. Diastereoselective, enantioselective, and
      enantiospecific construction of cyclic carbonates have been achieved by the
      application of this methodology.

PMID- 22382408
TI  - Evaluation of the predicted time-concentration profile of serum tulobuterol in
      human after transdermal application.
AB  - We proposed an in vitro/in vivo/in silico method for evaluating the clinical
      performance of matrix type transdermal therapeutic systems (TTSs). This method is
      based on the following four approaches: (1) drug release experiment, (2) in vitro
      penetration experiment using excised hairless mouse skin, (3) clinical
      pharmacokinetic study, and (4) mathematical model for evaluating the
      pharmacokinetic profile. The tulobuterol TTS was used as an example of a matrix
      type TTS in this study. The drug diffusion coefficient in the matrix device was
      calculated from the result of the release experiment. The drug diffusion
      coefficient and the partition coefficient in the skin were calculated from the
      results of in vitro skin penetration experiments where hairless mice and rats
      were used. Those parameters were used as substitutes of human. Further, these
      parameters were used for solving the governing partial differential equation on
      skin penetration. The time profiles of the serum concentration in human after
      applying the tulobuterol TTS were predicted and compared with the clinical data.
      The predicted profiles obtained from the data of hairless mice reproduced the
      influence of drug depletion adequately and well agreed with the clinical data,
      while those from the data of rats differed clearly in the initial rise. This
      method is useful for prediction of pharmacokinetic profiles of TTSs.

PMID- 22382409
TI  - Sesquiterpenes and other constituents from Dendranthema zawadskii var. latilobum.
AB  - Six new germacranolides, zawadskinolides A-F (1-6), and a new eudesmane
      glucoside, chrysantiloboside (7) were isolated from the aerial parts of
      Dendranthema zawadskii var. latilobum, along with thirteen known constituents.
      Their structures were elucidated by means of spectroscopic evidence. Bioassay
      showed that flavonoids such as apigenin (9), (-)-eriodictyol (10) and nepetin
      (12), as well as the sesquiterpene lactone, zawadskinolide F (6), inhibited
      nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7
      macrophage cells with IC50 values of 66.15, 132.55, 35.44, and 91.32 MUM,
      respectively.

PMID- 22382410
TI  - Taste-masking effect of physical and organoleptic methods on peppermint-scented
      orally disintegrating tablet of famotidine based on suspension spray-coating
      method.
AB  - Orally disintegrating tablets (ODTs) are useful for improving benefits for
      patients of various ages. Masking the unpleasant taste of a drug is an important
      factor in the compliance of patients who take ODTs. We evaluated the taste
      acceptability effects of various taste-masking methods on bitter famotidine ODTs
      as a clinical pharmacological study. The following methods were tested to compare
      taste-masking effects: physical masking by spray-coating famotidine with ethyl
      cellulose versus organoleptic masking with added sweetener and flavor. The ODT
      samples were prepared as single or combinations of each taste-masking method
      using a novel suspension spray-coating method including a placebo. A total of 31
      healthy volunteers were enrolled in this randomized, double-blind study and asked
      to score their bitterness, sweetness and total palate impressions by 100 mm
      visual analogue scale (VAS). VAS scores were significantly improved by the
      physical and organoleptic methods as compared to without taste-masked ODTs.
      Furthermore, the combination of both taste-masking methods was most effective for
      improving palatability and VAS scores were similar to those of placebo ODTs. The
      results of this study suggest that different taste-masking mechanisms function
      cooperatively.

PMID- 22382411
TI  - A new approach to characterization of insulin derived from different species
      using 1H-NMR coupled with multivariate analysis.
AB  - Most of the active components of polypeptides have a complex molecular structure,
      large molecular size. Such components may also be structurally heterogeneous.
      Therefore, development of a method that can confirm the consistency of
      polypeptides amino-acid sequences for product characterization is desirable. In
      general, it is extremely difficult to distinguish differences of a few amino acid
      residues in the 1H-NMR spectrum of polypeptides with molecular weights greater
      than several thousand. However, we have been able to distinguish between three
      insulin species differing in one to three amino acid residues using a combination
      of multivariate statistics and 1H-NMR spectra. These results demonstrate that
      this methodology could be useful for characterization of polypeptides.

PMID- 22382412
TI  - Novel ultra-cryo milling and co-grinding technique in liquid nitrogen to produce
      dissolution-enhanced nanoparticles for poorly water-soluble drugs.
AB  - A novel ultra-cryo milling micronization technique for pharmaceutical powders
      using liquid nitrogen (LN2 milling) was used to grind phenytoin, a poorly water
      soluble drug, to improve its dissolution rate. LN2 milling produced particles
      that were much finer and more uniform in size and shape than particles produced
      by jet milling. However, the dissolution rate of LN2-milled phenytoin was the
      same as that of unground phenytoin due to agglomeration of the submicron
      particles. To overcome this, phenytoin was co-ground with polyvinylpyrrolidone
      (PVP). The dissolution rate of co-ground phenytoin was much higher than that of
      original phenytoin, single-ground phenytoin, a physical mixture of phenytoin and
      PVP, or jet-milled phenytoin. X-Ray diffraction showed that the crystalline state
      of mixtures co-ground by LN2 milling remained unchanged. The equivalent
      improvement in dissolution, whether phenytoin was co-ground or separately ground
      and then mixed with PVP, suggested that even when co-ground, the grinding of PVP
      and phenytoin occurs essentially independently. Mixing original PVP with ground
      phenytoin provided a slight improvement in dissolution, indicating that the
      particle size of PVP is important for improving dissolution. When mixed with
      ground phenytoin, PVP ground by LN2 milling aided the wettability and dispersion
      of phenytoin, enhancing utilization of the large surface area of ground
      phenytoin. Co-grinding phenytoin with other excipients such as Eudragit L100,
      hypromellose, hypromellose acetate-succinate, microcrystalline cellulose,
      hydroxypropylcellulose and carboxymethyl cellulose also improved the dissolution
      profile, indicating an ultra-cryo milling and co-grinding technique in liquid
      nitrogen has a broad applicability of the dissolution enhancement of phenytoin.

PMID- 22382413
TI  - Development of dry salbutamol sulfate powder with high inhalation performance
      independent of inhalation patterns.
AB  - While dry powder inhalations are commonly used to treat pulmonary diseases, their
      clinical performance depends on patient inspiratory flow patterns. The purpose of
      this study was to develop a new powder with high and stable therapeutic
      performance for various patients. We applied the supercritical antisolvent (SCF)
      method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests
      of in vitro inhalation performance with a human inspiratory flow simulator
      revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled
      SS. When inspired, the unique structure seemed to be broken resulting in small
      fragments that could be delivered to the lungs. However, stability tests under
      physical stress showed tolerance for transportation and handling. In addition,
      optimization of the concentration of the SS solution applied to SCF method
      improved the in vitro inhalation performance of SS-SCF. These results indicated
      that a unique bulky SS powder prepared by the SCF method was useful for dry
      powder inhalation.

PMID- 22382414
TI  - Influence of peak inspiratory flow rates and pressure drops on inhalation
      performance of dry powder inhalers.
AB  - The aim of this study was to reveal the relationship between human inspiratory
      flow patterns and the concomitant drops in pressure in different inhalation
      devices, and the influence of the devices on inhalation performance. As a model
      formulation for inhalers, a physically mixed dry powder composed of salbutamol
      sulfate and coarse lactose monohydrate was selected. The drops in pressure at
      28.3 L/min of three inhalation devices, Single-type, Dual-type, and Reverse-type,
      was 1.0, 5.1, and 8.7 kPa, respectively. Measurements of human inspiratory
      patterns revealed that although the least resistant device (Single) had large
      inter- and intra-individual variation of peak flow rate (PFR), the coefficients
      of variation of PFR of the three devices were almost the same. In tests with a
      human inspiratory flow simulator in vitro, inhalation performance was higher, but
      the variation in inhalation performance in the range of human flow patterns was
      wider, for the more resistant device. To minimize the intra- and inter-individual
      variation in inhalation performance for the model formulation in this study, a
      formulation design that allows active pharmaceutical ingredient to detach from
      the carrier with a lower inhalation flow rate is needed.

PMID- 22382415
TI  - Characterization of selenium species in extract from Niboshi (a processed
      Japanese anchovy).
AB  - Fish are selenium rich foodstuffs and a major selenium source for the Japanese
      population. Niboshi is processed from Japanese anchovy (Engraulis japonicus) and
      commonly used to prepare soup stock for Japanese dishes. In this study, we
      characterized selenium species in the Niboshi extract by ultrafiltration, ion
      exchange chromatography and mass spectrometry. Selenium species in the Niboshi
      were more extractable by polar solvents (water and ethanol) than an apolar one
      (hexane) along with amino acids and proteinous species. Selenium in the water
      extract from the Niboshi was mostly ascribed to organoselenium compounds with a
      molecular mass less than 5 kDa. Although selenoamino acids and selenoproteins and
      their fragments were involved in the extract, a large portion of the selenium
      species appeared to be low-molecular-mass organoselenium compounds other than
      selenoamino acids and their derivatives. Ion-exchange chromatographic separations
      revealed that most of the selenium species in the extract possess anionic and/or
      amphoteric characteristics. One of these selenium species from the Niboshi
      extract was detected at m/z 577 for 80Se by mass spectrometry subsequent to ion
      pair extraction.

PMID- 22382416
TI  - New triterpenoid saponins from fruits specimens of Panax japonicus collected in
      Kumamoto and Miyazaki prefectures (1).
AB  - Seven new dammarane-type triterpenoid saponins, chikusetsusaponin FK1 (1),
      chikusetsusaponin FK2 (2), chikusetsusaponin FK3 (3), chikusetsusaponin FK4 (4),
      chikusetsusaponin FK5 (5), chikusetsusaponin FK6 (6), and chikusetsusaponin FK7
      (7), and eleven known triterpenoid saponins, ginsenoside Rb3 (9), ginsenoside Rc
      (10), chikusetsusaponin VI (11), ginsenoside Re (12), ginsenoside Rg1 (13),
      pseudo-ginsenoside RS1 (14), notoginsenoside R1 (15), chikusetsusaponin L5) (17),
      chikusetsusaponin L10 (18), chikusetsusaponin IVa (19), and chikusetsusaponin V
      (20), were isolated from the fruits of Panax japonicus C. A. MEYER, collected in
      Kumamoto prefecture, Japan, and two new dammarane-type triterpenoid saponin,
      chikusetsusaponin FK5 (5) and chikusetsusaponin FM1 (8), and five known
      triterpenoid saponins, ginsenoside Rb3 (9), ginsenoside Rc (10), ginsenoside Re
      (12), ginsenoside Rg1 (13), and floralquinquenoside E (16), were isolated from
      the fruits of P. japonicus C. A. MEYER, collected in Miyazaki prefecture, Japan.
      The structures of new chikusetsusaponins were elucidated on the basis of chemical
      and physicochemical evidences.

PMID- 22382417
TI  - Sesquiterpenes from an Egyptian herbal medicine, Pulicaria undulate, with
      inhibitory effects on nitric oxide production in RAW264.7 macrophage cells.
AB  - The methylene chloride-methanol (1 : 1) extract from the air-dried aerial parts
      of wild Pulicaria undulata collected in North Sinia, Egypt, showed inhibitory
      effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in
      RAW264.7 macrophages. From the extract, three new sesquiterpenes named 5alpha
      hydroperoxyivalin, 8-epi-xanthanol, and 8-epi-isoxanthanol were isolated together
      with four known sesquiterpenes. The structure of each new sesquiterpenes was
      determined on the basis of physicochemical and chemical evidence. In addition,
      all the sesquiterpenoids significantly inhibited the production of NO. Ivalin
      (IC50=2.0 MUM) and 2alpha-hydroxyalantolactone (1.8 MUM) showed particularly
      strong inhibitory effects, but had strong cytotoxic effects as well. Furthermore,
      ivalin and 2alpha-hydroxyalantolactone concentration-dependently reduced
      inducible NO synthase (iNOS) protein levels in RAW264.7 cells.

PMID- 22382418
TI  - High-throughput turbidimetric screening for heparin-neutralizing agents and low
      molecular-weight heparin mimetics.
AB  - Safer heparin-neutralizing agents are currently required to replace protamine,
      the use of which causes adverse effects such as anaphylaxia. Low-molecular-weight
      (LMW) heparin mimetics that potentiate antithrombin III (AT) action are also
      valuable as anti-thrombotics. This paper describes a high-throughput assay for
      both heparin-neutralizing agents and LMW heparin mimetics without the use of
      blood preparations. The assay is based on turbidimetric measurement of a solution
      of collagen, heparin, and a test compound. Native collagen molecules
      spontaneously form insoluble fibrils when transferred to a physiological buffer,
      and this process is inhibited by heparin. In the presence of a heparin
      neutralizing agent or an LMW heparin mimetic, the inhibitory effect of heparin is
      canceled and turbidity increase is retrieved. We demonstrated that this assay is
      effective in detecting potential agents with high reliability (Z' factor=0.9).
      The screening of a chemical library (34400 compounds) was further performed in a
      384-well format, and led to the identification of a novel heparin-neutralizing
      agent. Since this assay protocol is feasible for an automated high-throughput
      screening (HTS) system, it could enhance the lead seeking process for drugs
      related to heparin/heparan sulfate (HS) functions.

PMID- 22382419
TI  - Antimicrobial polyacetylenes from Panax ginseng hairy root culture.
AB  - Two new polyacetylenes, 1-hydroxydihydropanaxacol (3) and 17-hydroxypanaxacol
      (4), were isolated from Panax ginseng hairy root culture, along with
      dihydropanaxacol (1), panaxacol (2) and ginsenoyne D (5). Highly hydroxylated
      compounds 1-4 were isolated from the medium and compound 5, which was a
      biosynthetic precursor of compound 1, was isolated from the roots. Compounds 1-4
      showed antimicrobial activity against Staphylococcus aureus, Bacillus subtilis,
      Cryptococcus neoformans and Aspergillus fumigatus. It is suggested that P.
      ginseng plants release antimicrobial polyacetylenes into the surrounding soil
      from the roots as defense compounds.

PMID- 22382420
TI  - Regioselective intramolecular [3+2] annulation of allene-nitrones.
AB  - The regioselective intramolecular 1,3-dipolar cycloaddition of the
      phenylsulfonylallene-nitrone derivatives has been developed. This reaction showed
      that the distal double bond of the allene exclusively reacted with the nitrone
      group to produce the bicyclic isoxazolidine derivatives regardless of the
      substitution pattern on the allenyl moiety.

PMID- 22382421
TI  - Design, synthesis and inhibitory activities of 8-(substituted styrol
      formamido)phenyl-xanthine derivatives on monoamine oxidase B.
AB  - The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl
      xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B)
      inhibition were tested and the effect of substituents on the N-7, phenyl and the
      substituted positions are discussed. It was observed that compound 9b displayed
      significant MAO-B inhibition activity and selectivity, fluorine substitution
      plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido
      group at position-3' may enhance the activity and selectivity of 8-phenyl
      xanthine analogues. These results suggest that such compounds may be utilized for
      the development of new candidate MAO-B inhibitors for treatment of Parkinson's
      disease.

PMID- 22382422
TI  - Rapid and sensitive method for measuring the plasma concentration of doxorubicin
      and its metabolites.
AB  - Doxorubicin is an anti-cancer drug with a wide therapeutic range. However, it and
      its metabolites cause severe side effects, limiting its clinical use. Therefore,
      measuring the plasma concentration of doxorubicin and its metabolites is
      important to study the dosing regimen of doxorubicin. We developed a rapid and
      sensitive method by ultra-high-performance liquid chromatography with fluorescent
      detection for measuring the plasma concentration of doxorubicin and its
      metabolites in small volumes (around 10 MUL), enabling repeated measurements from
      the same mouse. The sensitivity of 7-deoxydoxorubicinolone, a major metabolite of
      doxorubicin, increased about 5 times than those ever reported using conventional
      HPLC, and the run time was within 3 min. The area under the curve (AUC0-24 h) of
      doxorubicin was 5.9 MUg h/mL similar to the value of 4.16 MUg h/mL obtained
      previously using a conventional HPLC method. This method would provide
      information that could be used to refine the therapeutic approach to doxorubicin
      use.

PMID- 22382423
TI  - Monoterpene glucosides from Ziziphora clinopodioides (Labiatae).
AB  - Three new monoterpene glucosides, ziziphoroside A (1), B (2), and C (3), together
      with fifteen known compounds were isolated from the whole herb of Z.
      clinopodioides. The structures of new compounds were determined primarily from 1D
      , 2D-NMR and circular dichroism (CD) spectroscopic analyses. The isolated
      compounds were evaluated for their inhibitory activity against nitric oxide (NO)
      production by lipopolysaccharide (LPS) and interferon (IFN)-gamma activated
      macrophages, RAW 264.7. Shizonepetoside A (8) and flavones (11, 12, 13) showed
      potent inhibitory activity against NO production.

PMID- 22382424
TI  - Development of a hypoxia-selective near-infrared fluorescent probe for non
      invasive tumor imaging.
AB  - A near-infrared fluorochrome, GPU-311, was designed, synthesized and evaluated
      for its application in non-invasive imaging of tumor hypoxia. Efficient synthesis
      was achieved by nucleophilic substitution and click chemistry ring using the
      bifunctional tetraethylene glycol linker 2 containing thiol and azide groups for
      the conjugation of the propargylated nitroimidazole 1 and the heptamethine
      cyanine dye 3 bearing a 2-chloro-1-cyclohexenyl ring. GPU-311 exhibited long
      excitation and emission wavelength (Ex/Em=785/802 nm) and a decent quantum yield
      (0.05). The water solubility and hydrophilicity of GPU-311 increased. After in
      vitro treatment of SUIT-2/HRE-Luc pancreatic cancer cells with GPU-311, a higher
      level of fluorescence was observed selectively in hypoxia than in normoxia.
      However, in vivo fluorescence imaging of a mouse xenograft model after GPU-311
      administration revealed inadequate accumulation of GPU-311 in tumors due to its
      rapid elimination through the liver.

PMID- 22382425
TI  - Molecular symmetry and biological activities of new symmetrical tris(2
      aminoethyl)amine derivatives.
AB  - In terms of molecular symmetry and bioactivity, new C3- and CS-symmetrical
      derivatives based on the tris(2-aminoethyl)amine scaffold were designed and
      synthesized. The synthesized compounds were evaluated for antiviral activity with
      herpes simplex virus type 1 (HSV-1) by a plaque reduction assay and for cytotoxic
      activity with Vero cells. Most of the compounds showed no significant anti-HSV-1
      activity, but some of the symmetrical derivatives showed high levels of cytotoxic
      activitiy.

PMID- 22382426
TI  - A selective intramolecular transacylation of taxoids accompanying with the
      oxetane ring opening.
AB  - A selective intramolecular transacylation from C-4 to C-5 of taxoids, which
      occurred simultaneously with the oxetane D-ring opening and was promoted by
      TiCl4, was presented. The optimal condition was found to be treatment of
      substrates in double dose of dichloromethane (per mg of substrate dissolved in 2
      mL DCM) with 1 eq of TiCl4 at 25 degrees C for 10 min.

PMID- 22382427
TI  - Impact of the closure of a large urban medical center: a qualitative assessment
      (part I).
AB  - This community health needs assessment-the first part of a mixed-methods project
      sought to qualitatively examine the impact of the closure of St. Vincent's
      Catholic Medical Center, a large not-for-profit hospital in NYC, on individuals
      who used its services. Key informant interviews with organizational leaders and
      focus groups with residents were conducted to understand hospital utilization,
      unmet health care needs, health care utilization and experiences post closure,
      perceptions of the most significant effect of the closing, and recommendations
      for improving health care in the community. Most respondents spoke positively of
      the hospital's accessibility, comprehensive, high-quality services, and its close
      relationship with the community. Conversely, experiences post-closure were
      largely negative, including decreased access, interrupted care, and loss of
      emergency and specialty care. Lack of information concerning medical records
      reflected a larger problem of poor planning and community outreach. Another issue
      was widespread anxiety in a community now lacking a hospital. Further, while the
      hospital's closure might cause inconveniences, these effects were described as
      more daunting to vulnerable groups. Our findings provide a consistent picture of
      a hospital highly regarded by residents, patients, and leaders of several health
      and social services organizations. Regardless of whether it should have been
      permitted to close (as raised by many respondents), the lack of advance planning
      and outreach to community members and patients remains a major criticism.
      Coordinated efforts to provide the community with information about health and
      social services in the area will respond to a clear need while reducing some of
      the complexity encountered with utilizing local health care services.

PMID- 22382430
TI  - Large amplitude Fourier transformed ac voltammetry at a rotating disc electrode:
      a versatile technique for covering Levich and flow rate insensitive regimes in a
      single experiment.
AB  - The theory for large amplitude Fourier transformed ac voltammetry at a rotating
      disc electrode is described. Resolution of time domain data into dc and ac
      harmonic components reveals that the mass transport for the dc component is
      controlled by convective-diffusion, while the background free higher order
      harmonic components are flow rate insensitive and mainly governed by linear
      diffusion. Thus, remarkable versatility is available; Levich behaviour of the dc
      component limiting current provides diffusion coefficient values and access to
      higher harmonics allows fast electrode kinetics to be probed. Two series of
      experiments (dc and ac voltammetry) have been required to extract these
      parameters; here large amplitude ac voltammetry with RDE methodology is used to
      demonstrate that kinetics and diffusion coefficient information can be extracted
      from a single experiment. To demonstrate the power of this approach, theoretical
      and experimental comparisons of data obtained for the reversible
      [Ru(NH(3))(6)](3+/2+) and quasi-reversible [Fe(CN)(6)](3-/4-) electron transfer
      processes are presented over a wide range of electrode rotation rates and with
      different concentrations and electrode materials. Excellent agreement of
      experimental and simulated data is achieved, which allows parameters such as
      electron transfer rate, diffusion coefficient, uncompensated resistance and
      others to be determined using a strategically applied approach that takes into
      account the different levels of sensitivity of each parameter to the dc or the ac
      harmonic.

PMID- 22382428
TI  - High prevalence of chronic non-communicable conditions among adult refugees:
      implications for practice and policy.
AB  - The global rise in non-communicable disease (NCD) suggests that US-based refugees
      are increasingly affected by chronic conditions. However, health services have
      focused on the detection of infectious disease, with relatively limited data on
      chronic NCDs. Using data from a retrospective medical record review of a refugee
      health program in the urban Northeast (n = 180), we examined the prevalence of
      chronic NCDs and NCD risk factors among adult refugees who had recently arrived
      in the US, with attention to region of origin and family composition. Family
      composition was included because low-income adults without dependent children are
      at high risk of becoming uninsured. We found that half of the adult refugees in
      this sample had at least one chronic NCD (51.1%), and 9.5% had three or more
      NCDs. Behavioral health diagnoses were most common (15.0%), followed by
      hypertension (13.3%). Half of adults were overweight or obese (54.6%). Chronic
      NCDs were somewhat more common among adults from Iraq, but this difference was
      not significant (56.8 vs. 44.6%). Chronic NCDs were common among adults with and
      without dependent children (61.4 vs. 44.6%, respectively), and these two groups
      did not significantly differ in their likelihood of having a chronic NCD after
      adjustment for age and gender (AOR = 0.78, 95% CI = 0.39, 1.55). This study
      suggests that chronic NCDs are common among adult refugees in the US, including
      refugees at high risk for uninsurance. We propose that refugee health services
      accommodate screening and treatment for chronic NCDs and NCD risk factors, and
      that insurance outreach and enrollment programs target recently arrived refugees.

PMID- 22382431
TI  - Is the inverted surface landing more suitable in evaluating ankle braces and
      ankle inversion perturbation?
AB  - OBJECTIVE: To investigate biomechanical (kinematic) differences between 2 ankle
      brace testing protocols: landing on an inverted surface (IS) and inversion drop
      on an inversion platform. DESIGN: Five trials in each of 4 dynamic movement
      conditions were performed: inversion drop and drop landing from 0.45 m onto an IS
      without and with an ankle brace. A 7-camera motion analysis system was used to
      obtain the 3-dimensional kinematics. A 2 * 2 (brace * movement) repeated measures
      analysis of variance was used to evaluate selected variables for inversion drop
      and IS landing. SETTING: Research laboratory. PATIENTS: Eleven healthy subjects
      participated in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Maximum
      ankle frontal plane and sagittal plane joint angles, range of motion, and maximum
      angular velocity. RESULTS: The IS landing resulted in significantly earlier
      maximum inversion, inversion velocities, dorsiflexion range of motion (ROM),
      contact dorsiflexion velocity, and maximum dorsiflexion velocity compared with
      the inversion drop. The ankle brace application during the IS landing reduced the
      contact plantarflexion angle, dorsiflexion ROM and maximum dorsiflexion velocity,
      and maximum inversion. CONCLUSIONS: The results from this study showed that the
      IS landing protocol produced significantly earlier maximum inversion angle and
      velocity and inversion velocities compared with the inversion drop protocol.
      These results showed that the IS landing is more demanding and should be
      considered in future investigations of ankle braces and lateral ankle
      performance/injury mechanisms.

PMID- 22382432
TI  - Impact of a surgical screening clinic for patients with knee osteoarthritis:  a
      descriptive study.
AB  - OBJECTIVE: To evaluate a surgical screening clinic for patients with knee
      osteoarthritis (OA) referred for total knee arthroplasty (TKA) and explore
      management before referral. DESIGN: Descriptive study using retrospective chart
      review. SETTING: Large Canadian teaching hospital. PARTICIPANTS: Patients with
      knee OA referred for TKA over a 1-year period. INTERVENTIONS: Patients underwent
      standardized assessment by physicians who practice sport medicine to determine
      eligibility for surgical consultation. MAIN OUTCOME MEASURES: Proportion of
      patients deemed eligible for surgical consultation and undergoing TKA, and
      conservative management options tried before clinic referral. RESULTS: Of the 327
      patients, 172 (52.6%) were referred to the surgeon, of whom 76% underwent TKA.
      Options used before referral were medications (92.0%), injections (41.3%), and
      physiotherapy (34.9%). Patients referred to the surgeon, compared with those who
      were not, were more likely to have met all referral criteria (86.5% vs 33.3%, P <
      0.001), tried 3 or more options (70.9% vs 49.7%, P < 0.01), used injections
      (58.7% vs 32.3%, P < 0.001), scored higher on the Hip-Knee Priority Tool (45 vs
      24, P < 0.001), and had been referred by a physician who practices sport medicine
      (88.2% vs 46.2%, P < 0.001). CONCLUSIONS: Orthopedic surgical screening by
      trained physicians using standardized tools halved the number of surgical
      consultations. Few conservative management options were tried before referral,
      indicating the need to enhance presurgical care for patients with knee OA.

PMID- 22382433
TI  - Validation of a new instrument for evaluating low back pain in the young athlete.
AB  - OBJECTIVE: To validate a back-specific instrument for functional assessment in
      the young athlete for clinical and research purposes, the Micheli Functional
      Scale (MFS). DESIGN: Prospective cohort study, Diagnostic Level II. SETTING:
      Division of Sports Medicine Clinic, Children's Hospital Boston. PARTICIPANTS:
      Male and female patients aged 12 to 22 with and without low back pain.
      INTERVENTIONS: Patients presenting with back pain were compared with a control
      group of patients presenting with complaints other than back pain. Both groups
      were given the modified Oswestry Low Back Pain Disability Questionnaire (ODQ) and
      MFS. MAIN OUTCOME MEASURES: Micheli Functional Scale and ODQ score correlations.
      RESULTS: A total of 94 patients were enrolled (44 patients with low back pain and
      50 patients without low back pain). Ages ranged from 12 to 22 for both groups,
      with no differences in age (P = 0.07) or gender (P = 0.50). Patients with back
      pain had significantly higher ODQ scores (median, 32 points) and MFS scores
      (median, 47 points) compared with controls (median, 0 points; P < 0.0001). These
      results held for male and female patients and younger (12-16.99 years) and older
      (17-22 years) age groups. The Pearson correlation coefficient showed a high
      positive correlation between MFS scores and ODQ scores (Pearson r = 0.90, P <
      0.0001). Cronbach level indicated excellent item reliability on the MFS (alpha =
      0.904, P < 0.0001). CONCLUSIONS: The MFS is a valid instrument for assessing pain
      and functional levels in the young athlete. This scale considers pain, athletic
      function, and athletic disability.

PMID- 22382434
TI  - Sex-specific variation in brown-headed cowbird immunity following acute stress: a
      mechanistic approach.
AB  - There is some discrepancy in the literature regarding whether acute stress is
      immunostimulatory or immunosuppressive. Studies of domesticated (laboratory and
      food) animals and humans typically indicate that acute stress is
      immunostimulatory, whereas studies of non-domesticated species document both
      immunostimulatory and immunosuppressive results. Few studies have examined the
      mechanisms responsible for changes in immune activity in species other than those
      classically used in laboratory research. We examined the effect of both acute
      stress and exogenous corticosterone (CORT) on the bactericidal capacity (BC) of
      blood plasma from captive, wild-caught brown-headed cowbirds (Molothrus ater) to
      determine if CORT is responsible for changes in levels of immune activity. We
      conducted "stress tests" in which we handled birds to elicit a stress response
      and then measured the birds' total CORT and BC at 30 or 90 min post-stressor. We
      also conducted non-invasive tests in which we administered exogenous CORT by
      injecting it into mealworms that were fed to the cowbirds remotely. Total, free,
      and bound CORT levels, corticosteroid binding globulins (CBGs), and BC at 7 or 90
      min post-mealworm ingestion were measured. Both males and females exhibited
      significant increases in total CORT following handling stress and the
      administration of exogenous CORT. Experimental males and females also exhibited a
      significant increase in CBG capacity at 7 min post-mealworm ingestion compared to
      controls. Male cowbirds exhibited a significant decline in their BC following
      both handling stress and the administration of exogenous CORT whereas female
      cowbirds exhibited no decline under either condition. Female CBG levels were not
      different than those of males, suggesting that differences in BC could be due to
      differences between the sexes in the number of corticosteroid receptors which,
      along with CBGs, regulate the stress response. Female cowbirds may modulate their
      stress response as an adaptive life-history strategy for maximizing current
      reproduction.

PMID- 22382435
TI  - Homocysteine and cognition in first-episode psychosis patients.
AB  - In the last years, there has been growing evidence linking elevated homocysteine
      levels with cognitive dysfunction in several neurological and neuropsychiatric
      diseases. The aim of the present study was to investigate the potential
      relationship between elevated homocysteine levels and cognitive deficits in first
      episode psychosis patients. Plasma levels and cognitive performance of 139
      patients and 99 healthy volunteers were compared. Patients were classified as
      elevated homocysteine (>90 percentile for controls) and normal and compared on 22
      cognitive outcome measures grouped into cognitive domains known to be impaired in
      schizophrenia. Patients had a statistically significant increase in plasmatic
      homocysteine levels. In addition, they presented with significantly increased
      cognitive deficits. However, no relationship between homocysteine levels and
      cognitive impairment was detected. These results suggest the need for further
      studies to clarify the role of homocysteine in the etiology and prognosis of
      psychosis.

PMID- 22382436
TI  - Molecular mechanisms underlying the function diversity of transcriptional factor
      IclR family.
AB  - The IclR family transcriptional factor is widespread and involves in diverse
      bacterial physio-pathological events, such as primary and secondary metabolism,
      virulence, quorum sensing, sporulation. Unlike other transcriptional factors
      which function as either activators or repressors, IclR can assume both role
      simutaneously. Its N-terminal domain possesses a helix-turn-helix DNA binding
      motif which can dimerize or tetramerize to bind target promoters, while the C
      terminal domain is for the effector binding. The function of IclR varies with the
      effectors bound. Escherichia coli transcription factor IclR is the archetype of
      this family, which regulates the aceBAK operon responsible for the glyoxylate
      shunt. The sophisticated regulatory mechanisms underlying iclR was largely based
      on E. coli iclR. Information concerning the pathogen IclR, especially those of
      Mycobacterium tuberculosis is poor, and is pivotal to our understanding of its
      biology and development of new effective TB control measures.

PMID- 22382438
TI  - A computational experiment to study hydrogenations of various unsaturated
      compounds catalyzed by a rationally designed metal-free catalyst.
AB  - Metal-free hydrogenation has been proposed to be a green alternative to the
      conventional hydrogenation mediated by precious transition metal complexes.
      Thanks to the discovery of FLP (frustrated Lewis pair) chemistry, the field has
      recently witnessed significant progress. Inspired by the FLP idea of synergically
      utilizing the catalytic effects of Lewis acid and base, we previously proposed a
      strategy to construct metal-free active sites for H(2) activation and designed a
      metal-free molecule (1) that shows high reactivity toward H(2). Encouraged by the
      recent experimental successes in applying the strategy, we have computationally
      explored if 1 can go further to serve as a catalyst to promote the hydrogenations
      of various unsaturated compounds examined by ethylene (CH(2)=CH(2) (4)), silyl
      enol ether (CH(2)=C(Me)OSiMe(3) (5)), imines (Me(2)C=NMe (6) and Ph(Me)C=NMe
      (7)), and ketone (Ph(Me)C=O (9)). The energetic results predicted at the M05
      2X(IEFPCM, solvent = THF)/6-311++G** level indicate that these reactions have
      feasible kinetics and thermodynamics for experimental realization. The hydride
      transfer step follows the concerted mechanism, although the transfer process has
      asynchronous character for silyl enol ether (5) and imines (6 and 7). In
      addition, we have investigated the binding of CO(2) to 1 and the 1-mediated
      hydrogenation of CO(2).

PMID- 22382437
TI  - [Preclinical imaging in animal models of radiation therapy].
AB  - CLINICAL/METHODICAL ISSUE: Modern radiotherapy benefits from precise and targeted
      diagnostic and pretherapeutic imaging. STANDARD RADIOLOGICAL METHODS: Standard
      imaging modalities, such as computed tomography (CT) offer high morphological
      detail but only limited functional information on tumors. METHODICAL INNOVATIONS:
      Novel functional and molecular imaging modalities provide biological information
      about tumors in addition to detailed morphological information. PERFORMANCE:
      Perfusion magnetic resonance imaging (MRI) CT or ultrasound-based perfusion
      imaging as well as hybrid modalities, such as positron emission tomography (PET)
      CT or MRI-PET have the potential to identify and precisely delineate viable
      and/or perfused tumor areas, enabling optimization of targeted radiotherapy.
      Functional information on tissue microcirculation and/or glucose metabolism allow
      a more precise definition and treatment of tumors while reducing the radiation
      dose and sparing the surrounding healthy tissue. ACHIEVEMENTS: In the development
      of new imaging methods for planning individualized radiotherapy, preclinical
      imaging and research plays a pivotal role, as the value of multimodality imaging
      can only be assessed, tested and adequately developed in a preclinical setting,
      i.e. in animal tumor models. PRACTICAL RECOMMENDATIONS: New functional imaging
      modalities will play an increasing role for the surveillance of early treatment
      response during radiation therapy and in the assessment of the potential value of
      new combination therapies (e.g. combining anti-angiogenic drugs with
      radiotherapy).

PMID- 22382439
TI  - Undocumented pregnant women: what does the literature tell us?
AB  - The present literature review was conducted to determine what information has
      been published on the topic of undocumented pregnant migrants. Scientific
      databases and gray literature sources were searched for articles published
      between January 1967 and September 2010. Eighty-seven articles met the inclusion
      criteria and were reviewed. A final sample of 23 articles was included in the
      review. Existing evidence suggests that pregnant undocumented migrants living in
      Western societies tend to be younger, unmarried, and more likely to be employed
      in the domestic sector than documented migrants and permanent residents. They
      have less access to prenatal care and consult later in pregnancy than controls.
      Findings concerning delivery and birth outcomes are conflicting and subject to
      several biases. Little has been published on programs to address the needs of
      undocumented pregnant women living in Western countries. More research on the
      particular health and social issues faced by these women is needed.

PMID- 22382440
TI  - Factors associated with sexual and reproductive health care by Mexican immigrant
      women in New York City: a mixed method study.
AB  - Limited research has examined barriers to sexual and reproductive health (SRH)
      services for Mexican immigrant women, especially those living in the eastern
      United States. This mixed-method study describes SRH care utilization and
      barriers experienced by female Mexican immigrants living in New York City. One
      hundred and fifty-one women completed surveys, and twenty-three also participated
      in focus groups. Usage of SRH care was low apart from prenatal services. The
      highest barriers included cost, language differences, child care, and poor
      service quality. After adjusting for insurance status, barriers were associated
      with receipt of gynecological care from a clinic or private doctor. Greater SRH
      knowledge was associated with current contraceptive use and a recent PAP test.
      Women reported that promotoras could increase information about SRH and decrease
      barriers. Results suggest that in a context where services are geographically
      available, health care utilization is impacted by lack of knowledge and
      structural barriers such as language, cost, and child care. Implications for
      community outreach are discussed.

PMID- 22382441
TI  - Social factors associated with the knowledge about HIV of the immigrants from
      China, Latin America, the Maghreb and Senegal in the Basque Country (Spain).
AB  - The objective of this study was to identify the social factors that explain the
      differences in knowledge with regards to HIV/AIDS among immigrants in the Basque
      Country (Spain). We conducted a cross-sectional study based on information
      obtained in the Basque Health Survey for 754 immigrants from: 86 China, 368 Latin
      America, 237 the Maghreb and 74 Senegal. Odds ratios (95% CI) were calculated
      from logistic regression models to measure the degree of association between
      inadequate knowledge regarding transmission, prevention and places where HIV
      testing is offered, and the independent variables. We found that this inadequate
      knowledge is associated with place of birth, sex, a lower level of education,
      immigration status, difficulties in understanding Spanish, and not receiving
      advice about AIDS in primary care. These findings indicate that initiatives must
      be developed to promote equity in the provision of healthcare through clinical
      guidelines, including details of the specific needs of different groups of
      immigrants and considering gender issues.

PMID- 22382442
TI  - Obesity and physical activity in the daily life of patients with COPD.
AB  - BACKGROUND: The aim of this study was to investigate the differences in body
      composition between physically active and inactive patients with chronic
      obstructive pulmonary disease (COPD) and the relationship of obesity [according
      to body mass index (BMI) and percentage of fat mass (%FM)] with physical activity
      in the daily life (PADL) in this population. METHODS: Body composition
      (bioelectrical impedance analysis) and level of PADL (activity monitors DynaPort
      and SenseWear) were evaluated in 74 patients with COPD (45 men, 65 +/- 9 years
      old, FEV(1) = 40 +/- 15%pred, BMI = 27 +/- 6 kg m(-2)). Patients were divided in
      two groups: physically active (>30 min/day of physical activity of at least
      moderate intensity, or TPA > moderate) and inactive (did not achieve these
      recommendations). The sample was also classified according to BMI (underweight,
      normal weight, overweight, and obese) and their %FM (moderate obesity, high
      obesity, and morbid obesity). RESULTS: In the whole group, TPA > moderate
      correlated weakly with BMI (r = -0.28; p = 0.02) and FM (r = -0.30; p = 0.001)
      but not with fat-free mass (FFM) (r = -0.18; p = 0.13). Physically inactive
      patients had higher body weight (p = 0.002), FM (p = 0.0005), and lower FFM as %
      of body weight (p = 0.03) than active patients. Obese patients (according to BMI)
      had a worse PADL level than underweight and normal-weight patients (p < 0.0001).
      A poorer PADL level occurred in morbidly obese patients (p = 0.01) despite the
      weak correlation between FM and TPA > moderate in the whole group. CONCLUSION:
      Physically active patients with COPD have proportionally more FFM and less FM
      than inactive patients. More pronounced physical inactivity occurs in obese
      patients, although body composition does not qualify as an important correlate
      factor of the level of PADL in patients with COPD.

PMID- 22382443
TI  - Impact of nitrogen concentration on validamycin A production and related gene
      transcription in fermentation of Streptomyces hygroscopicus 5008.
AB  - Validamycin A (VAL-A) is an important and widely used agricultural antibiotic. In
      this study, statistical screening designs were applied to identify significant
      medium variables for VAL-A production and to find their optimal levels. The
      optimized medium caused 70% enhancement of VAL-A production. The difference
      between optimized medium and original medium suggested that low nitrogen source
      level might attribute to the enhancement of VAL-A production. The addition of
      different nitrogen sources to the optimized medium inhibited VAL-A production,
      which confirmed the importance of nitrogen concentration for VAL-A production.
      Furthermore, differences in structural gene transcription and enzyme activity
      between the two media were assayed. The results showed that lower nitrogen level
      in the optimized medium could regulate VAL-A production in gene transcriptional
      level. Our previous study indicated that the transcription of VAL-A structural
      genes could be enhanced at elevated temperature. In this work, the increased
      fermentation temperature from 37 to 42  degrees C with the optimized medium
      enhanced VAL-A production by 39%, which testified to the importance of structural
      gene transcription in VAL-A production. The information is useful for further VAL
      A production enhancement.

PMID- 22382444
TI  - Bi-stage control of dissolved oxygen to enhance cyclic adenosine monophosphate
      production by Arthrobacter A302.
AB  - Experiments confirmed dissolved oxygen (DO) definitely affects cyclic adenosine
      monophosphate (cAMP) production by Arthrobacter A302. Production of cAMP by batch
      fermentation was investigated under various DO conditions. A two-stage DO control
      strategy was proposed to achieve optimal production of cAMP based on the kinetic
      analysis: the DO level was controlled at 40% during the first 18 h and then
      switched to 30%. Relatively high cAMP production (9.9 g L(-1)) was achieved by
      applying this strategy. The cAMP productivity (0.14 g L(-1) h(-1)) was also
      successfully improved by 85.1, 59.3, 15.1 and 28.0%, compared to cases in which
      DO was uncontrolled or DO levels were held at 20, 30 and 40%, respectively. This
      is the first report of the use of a two-stage DO control strategy in cAMP
      production, and it was verified to be an effective method for enhancing the cAMP
      yield via this strain.

PMID- 22382445
TI  - Plasmonic enhancement of gold nanoparticles on photocycloreversion reaction of
      diarylethene derivatives depending on particle size, distance from the particle
      surface, and irradiation wavelength.
AB  - We newly synthesized various sized gold nanoparticles covered with photochromic
      polymers consisting of diarylethenes with various structures to investigate an
      effect of the gold nanoparticles on the photocycloreversion reaction of the
      diarylethene chromophores upon irradiation with visible light. The gold
      nanoparticles covered with the photochromic polymers exhibited reversible changes
      in localized surface plasmon resonance (LSPR) absorption along with the
      photochromic reaction depending on the diameter of the particle, the distance
      between the gold surface and the chromophore, and the structure of the
      diarylethene chromophore. The rate of the photocycloreversion reaction of the
      chromophores around the particle was enhanced by the gold nanoparticles and the
      degree of the enhancement was affected by the diameter of the particle and the
      distance from the gold surface, while a structural difference in the diarylethene
      chromophore had no effect on the degree of the enhancement. The larger
      enhancement of the photocycloreversion reaction was observed by irradiation at
      longer wavelength side than visible light corresponding to the LSPR frequency.

PMID- 22382446
TI  - Air pollution intervention: study links use of face masks to improved
      cardiovascular outcomes.

PMID- 22382447
TI  - Implant rehabilitation in patients with oral lichen planus: an overview.
AB  - OBJECTIVES: Implant rehabilitation in oral lichen planus (OLP) is a major
      challenge for clinicians and patients. There is limited scientific evidence,
      primarily case reports and small case series. We conducted a literature review of
      data on the effectiveness and safety of implant rehabilitation in OLP patients.
      MATERIAL AND METHODS: We searched MEDLINE, Embase and Cochrane databases for
      articles on implant placement in OLP patients (searches from 1980 to 2011).
      RESULTS: Eight studies (41 OLP patients rehabilitated with 135 implants) met the
      inclusion criteria. Survival rate of implants was 94.8% over a mean follow-up of
      56.5 months. CONCLUSIONS: There is very limited evidence on the safety and
      benefits of implant placement in OLP patients. Implant loss appears not to be
      directly related to OLP, but linked to factors such as parafunctions, poor bone
      quality and marginal mandibular resection. The benefits and harms of using
      implants in people with OLP require thorough evaluation in properly designed
      randomised, controlled studies. CLINICAL RELEVANCE: OLP is not an absolute
      contraindication for implant insertion and there is no increased risk of failure.
      Implants should be positioned only if mucosal signs and symptoms are in the
      remission phase. A careful oral hygiene and frequent follow-up are the main
      recommendations in OLP patients rehabilitated with implants.

PMID- 22382448
TI  - An in vitro comparison of subjective image quality of panoramic views acquired
      via 2D or 3D imaging.
AB  - OBJECTIVES: The objective of this study is to compare subjective image quality
      and diagnostic validity of cone-beam CT (CBCT) panoramic reformatting with
      digital panoramic radiographs. MATERIALS AND METHODS: Four dry human skulls and
      two formalin-fixed human heads were scanned using nine different CBCTs, one multi
      slice CT (MSCT) and one standard digital panoramic device. Panoramic views were
      generated from CBCTs in four slice thicknesses. Seven observers scored image
      quality and visibility of 14 anatomical structures. Four observers repeated the
      observation after 4 weeks. RESULTS: Digital panoramic radiographs showed
      significantly better visualization of anatomical structures except for the
      condyle. Statistical analysis of image quality showed that the 3D imaging
      modalities (CBCTs and MSCT) were 7.3 times more likely to receive poor scores
      than the 2D modality. Yet, image quality from NewTom VGi(r) and 3D Accuitomo
      170(r) was almost equivalent to that of digital panoramic radiographs with
      respective odds ratio estimates of 1.2 and 1.6 at 95% Wald confidence limits. A
      substantial overall agreement amongst observers was found. Intra-observer
      agreement was moderate to substantial. CONCLUSIONS: While 2D-panoramic images are
      significantly better for subjective diagnosis, 2/3 of the 3D-reformatted
      panoramic images are moderate or good for diagnostic purposes. CLINICAL
      RELEVANCE: Panoramic reformattings from particular CBCTs are comparable to
      digital panoramic images concerning the overall image quality and visualization
      of anatomical structures. This clinically implies that a 3D-derived panoramic
      view can be generated for diagnosis with a recommended 20-mm slice thickness, if
      CBCT data is a priori available for other purposes.

PMID- 22382449
TI  - Influence of MMP-8 promoter polymorphism in early osseointegrated implant
      failure.
AB  - OBJECTIVE: Dental implants consist in the treatment of choice to replace tooth
      loss. The knowledge that implant loss tends to cluster in subsets of individuals
      may indicate that host immuneinflammatory response is influenced by genetic
      factors. In fact, genetic polymorphisms influence the osseointegration process.
      The objective of this study was investigate the possible relationship between C
      799T polymorphism in matrix metalloproteinase 8 (MMP-8) gene and early implant
      failure in nonsmoker patients. METHODS AND MATERIALS: Subjects were divided into
      two groups: control group (100 patients with one or more healthy implants) and
      test group (80 patients that had suffered one or more early implant failures).
      Genomic DNA from oral mucosa was amplified by PCR and analyzed by restriction
      endonucleases. The significance of the differences in observed frequencies of
      polymorphisms was assessed by Chi-square. RESULTS: Statistical analysis shows
      that in the MMP-8 gene, the T allele in 76.25% in the test group and the T/T
      genotype, 63.75% in the same group, may predispose to early loss of implants
      osseointegrated. CONCLUSION: These results suggest that polymorphism in the
      promoter region of MMP-8 gene is associated with early implant failure. This
      polymorphism can be a genetic marker to risk of implant loss. CLINICAL RELEVANCE:
      The determination of this genetic pattern in osseointegration would enable the
      identification of individuals at higher risk to loss implant. Thus, genetic
      markers will be identified, contributing to an appropriate preoperative selection
      and preparation of strategies for prevention and therapy individualized to
      modulate the genetic markers and increase the success rate of treatments.

PMID- 22382450
TI  - Current world literature.

PMID- 22382452
TI  - The need to know--therapeutic privilege: a way forward.
AB  - Providing patients with information is fundamental to respecting autonomy.
      However, there may be circumstances when information may be withheld to prevent
      serious harm to the patient, a concept referred to as therapeutic privilege. This
      paper provides an analysis of the ethical, legal and professional considerations
      which impact on a decision to withhold information that, in normal circumstances,
      would be given to the patient. It considers the status of the therapeutic
      privilege in English case law and concludes that, while reference is made to
      circumstances when information (primarily in relation to risk disclosure) may be
      withheld, further clarification is required on the status of therapeutic
      privilege. I suggest there has been shift in English law relating to the standard
      of information disclosure towards one set by the test of the reasonable, prudent
      patient. It is this shift that necessitates the existence of a therapeutic
      privilege which enables doctors to withhold information that would usually be
      given to the patient in order to prevent serious harm. I then explore the
      professional guidance in relation to information disclosure and how this relates
      to the legal position. There are strong ethical arguments in favour of disclosure
      of information to patients. In light of these, further clarification is required
      to identify and define the grounds on which this exception exists, the
      information that could lawfully be withheld and how this exception extends to
      rest of the health care team, particularly nurses. As such, explicit ethical and
      legal scrutiny of therapeutic privilege is needed in order to consider how this
      concept might be articulated, constrained and regulated.

PMID- 22382453
TI  - The efficacy evaluation of cryosurgery in pancreatic cancer patients with the
      expression of CD44v6, integrin-beta1, CA199, and CEA.
AB  - Increased expression of cell adhesion molecule CD44v6, integrin-beta1,
      carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA) are closely
      associated with the progression and metastasis of numerous cancers. In this
      study, peripheral blood mononuclear cell (PBMC) and serum samples were collected
      from 37 pancreatic cancer patients and 12 healthy people. A novel triplex TaqMan
      real-time reverse transcription polymerase chain reaction assay was used to
      measure the expression levels of CD44v6 and integrin-beta1 gene in PBMCs, while
      chemiluminescence and enzyme-linked immunosorbent assay were used to measure the
      levels of CA199 and CEA expression in serum. The results showed that both the
      levels of CD44v6 and integrin-beta1 expression had significant correlation with
      clinical stage, lymph node, and liver metastasis of pancreatic cancer (P < 0.05).
      Age, tumor size, tumor differentiation, clinical stage, lymph nodes, and liver
      metastasis were significantly associated with the levels of CA199 and CEA
      expression (P < 0.05). The levels of CD44v6, integrin-beta1, CA199, and CEA
      expression in the patients prior cryosurgery and chemotherapy were significantly
      higher than those in the control group (P < 0.05), whereas no significant
      difference was found between the patients 1 month post cryosurgery and control
      group (P > 0.05). The expression levels of CD44v6, integrin-beta1, CA199, and CEA
      in the patients 1 month post cryosurgery were significantly lower than those in
      the patients prior cryosurgery (P < 0.05). Interestingly, no significant
      difference was found for the CD44v6, integrin-beta1, CA199, and CEA levels
      between the patients prior and post-chemotherapy (P > 0.05). The higher
      expression of CD44v6, integrin-beta1, CA199, and CEA are closely related to the
      progression and metastasis of pancreatic cancer and may play a important role in
      the curative evaluation of cryosurgery of pancreatic cancer.

PMID- 22382454
TI  - Enhanced adenovirus transduction of hMSCs using 3D hydrogel cell carriers.
AB  - Hydrogels are increasingly being investigated as a means to implant cells for
      tissue engineering. One way to further enhance the repair response would be to
      combine the hydrogel cell carrier with gene transfer. Gene therapy, using
      adenoviral vectors, is an effective way to provide transient delivery of
      bioactive factors. However, current protocols require further optimization,
      especially if they are to be transferred into the clinic. This study opted to
      compare the efficiency of protocols for standard two-dimensional (2D) versus
      three-dimensional (3D), adenoviral-mediated, transduction of human mesenchymal
      stem cells. Two different multiplicities of infection were tested. After
      encapsulation in fibrin, alginate or agarose, cells were cultured for 28 days.
      Transduction in 3D showed a much higher efficiency, compared to standard 2D
      transduction protocols. In 3D, the amount of transgene produced was significantly
      higher, for every condition investigated. Furthermore, transduction in 3D does
      not require a cell culture step and can be conducted within the operating
      theatre. In conclusion, it was demonstrated that 3D transduction, using
      adenoviral vectors, is superior to standard transduction protocols in 2D. It
      therefore, might help increasing its administration in tissue engineering and
      clinical applications.

PMID- 22382455
TI  - Disability and decline in physical function associated with hospital use at end
      of life.
AB  - BACKGROUND: Hospital use near the end of life is often undesirable to patients,
      represents considerable Medicare cost, and varies widely across regions.
      OBJECTIVE: To concurrently examine regional and patient factors, including
      disability and functional decline, associated with end-of-life hospital use.
      DESIGN/PARTICIPANTS: We sampled decedents aged 65 and older (n = 2,493) from the
      Health and Retirement Study (2000-2006), and linked data from individual Medicare
      claims and the Dartmouth Atlas of Health Care. Two-part regression models
      estimated the relationship between total hospital days in the last 6 months and
      patient characteristics including physical function, while adjusting for regional
      resources and hospital care intensity (HCI). KEY RESULTS: Median hospital days
      was 7 (range = 0-183). 53% of respondents had functional decline. Compared with
      decedents without functional decline, those with severe disability or decline had
      more regression-adjusted hospital days (range 3.47-9.05, depending on category).
      Dementia was associated with fewer days (-3.02); while chronic kidney disease
      (2.37), diabetes (2.40), stroke or transient ischemic attack (2.11), and
      congestive heart failure (1.74) were associated with more days. African Americans
      and Hispanics had more days (5.91 and 4.61, respectively). Those with family
      nearby had 1.62 fewer days and hospice enrollees had 1.88 fewer days. Additional
      hospital days were associated with urban residence (1.74) and residence in a
      region with more specialists (1.97) and higher HCI (2.27). CONCLUSIONS:
      Functional decline is significantly associated with end-of-life hospital use
      among older adults. To improve care and reduce costs, health care programs and
      policies should address specific needs of patients with functional decline and
      disability.

PMID- 22382456
TI  - Newer is not always better: all antihypertensive medications do not equally
      reduce cardiovascular risk.

PMID- 22382457
TI  - Racial disparities in the association between variants on 8q24 and prostate
      cancer: a systematic review and meta-analysis.
AB  - Recent studies implicate single nucleotide polymorphisms (SNPs) within the 8q24
      region as a risk factor for prostate cancer (PCa). New developments suggest that
      8q24 encodes regulators of the nearby MYC gene, a known oncogene. In order to
      better understand the implications of SNPs in this region, we performed meta
      analyses, stratified by race, of seven SNPs and one microsatellite marker
      previously identified as risk loci on the 8q24 region of the genome. In addition,
      we reviewed the literature examining the possible associations between these
      polymorphisms and clinicopathological features of PCa. The results of the meta
      analyses indicate that rs6983267, rs1447295, rs6983561, rs7837688, rs16901979,
      and DG8S737 are significantly associated with a higher risk for PCa for at least
      one race, whereas the variants rs13254738 and rs7000448 are not. The degree of
      association and frequency of the causative allele varied among men of different
      races. Though several studies have demonstrated an association between certain
      8q24 SNPs and clinicopathological features of the disease, review of this topic
      revealed conflicting results.

PMID- 22382458
TI  - Adult brainstem gliomas.
AB  - Brainstem gliomas are uncommon in adults and account for only 1%-2% of
      intracranial gliomas. They represent a heterogeneous group of tumors that differ
      from those found in their pediatric counterparts. In adults, a low-grade
      phenotype predominates, which is a feature that likely explains their better
      prognosis compared to that in children. Because biopsies are rarely performed,
      classifications based on the radiological aspect of magnetic resonance imaging
      results have been proposed to establish treatment strategies and to determine
      outcomes: (a) diffuse intrinsic low-grade, (b) enhancing malignant glioma, (c)
      focal tectal gliomas, and (d) exophytic gliomas. Despite significant advances in
      neuroradiology techniques, a purely radiological classification remains imperfect
      in the absence of a histological diagnosis. Whereas a biopsy may often be
      reasonably avoided in the diffuse nonenhancing forms, obtaining histological
      proof seems necessary in many contrast-enhanced brainstem lesions because of the
      wide variety of differential diagnoses in adults. Conventional radiotherapy is
      the standard treatment for diffuse intrinsic low-grade brainstem gliomas in
      adults (the median survival is 5 years). In malignant brainstem gliomas,
      radiotherapy is the standard treatment. However, the possible benefit of combined
      radiotherapy and chemotherapy (temozolomide or other agents) has not been
      thoroughly evaluated in adults. The role of anti-angiogenic therapies in
      brainstem gliomas remains to be defined. A better understanding of the biology of
      these tumors is of primary importance for identifying homogeneous subgroups and
      for improving therapy options and outcomes.

PMID- 22382459
TI  - Evaluation of an educational program to improve communication with patients about
      early-phase trial participation.
AB  - BACKGROUND: Discussing early-phase cancer trials is challenging; most offer
      little personal benefit to patients with life-limiting illnesses who frequently
      have a poor understanding of and misconceptions about the therapeutic aims. We
      evaluated an evidence-based training program aimed at enhancing communication.
      METHODS: Prior to and after the intervention, 47 health care professionals (HCPs)
      experienced in early-phase trial recruitment were audio taped discussing trials
      with patient simulators who completed postinterview evaluations. Coders rated the
      interviews for the presence of information areas required to elicit ethical
      consent. HCPs reported their self-confidence on 15 different aspects of trial
      discussion. RESULTS: Significant objective and subjective improvements in
      communication were found after the workshop. Analyses of audio tapes showed
      positive shifts in: establishing the patient's knowledge of their prognosis (odds
      ratio [OR], 2.7; p = .002), discussing symptomatic care (OR, 3.8; p < .001), the
      aims of the trial (OR, 2.6; p =.002), and the unlikelihood of medical benefit
      (OR, 3.0; p = .021). Patient simulator ratings showed improvements in: the
      awareness of palliative care and symptom control (OR, 2.1; p = .004), the
      voluntariness of participation (OR, 3.7; p = .015), the opportunity to ask
      questions (OR, 2.9; p = .044), and the time to consider participation (OR, 6.1; p
      = .009). HCPs' self-confidence increased significantly for all 15 items (OR
      range, 1.5-2.9; p <= .001). CONCLUSION: This short, intensive workshop changed
      communication skills competency and self-efficacy in ways likely to promote
      valid, ethically informed consent from patients contemplating trial entry.

PMID- 22382460
TI  - Modeling the 5-fluorouracil area under the curve versus dose relationship to
      develop a pharmacokinetic dosing algorithm for colorectal cancer patients
      receiving FOLFOX6.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is administered based on standard body surface
      area (BSA) dosing. BSA administration results in highly variable exposure,
      measured as the area under the concentration-time curve (AUC). An immunoassay
      (OnDose(r); Myriad Genetic Laboratories, Inc., Salt Lake City, UT) that measures
      plasma 5-FU concentration and reports an AUC in mg . h/L has been developed to
      optimize therapy using pharmacokinetic (PK) dosing. The results of an analysis to
      model the 5-FU AUC-dose relationship are presented. METHODS: A set of 589
      sequential patients from a clinical database receiving 5-FU, leucovorin, and
      oxaliplatin (the FOLFOX6 regimen) for colorectal cancer (CRC) treatment was
      analyzed. A subset including only patients who had at least two consecutive
      cycles tested, received 1,600-3,600 mg/m2 of continuous infusion 5-FU during the
      initial test cycle, and had a blood sample collected after >=18 hours, was used
      to conduct regression modeling of the change in AUC versus change in dose.
      RESULTS: A simple regression model with R(2) = 0.51 developed over n = 307 cycle
      pair observations characterizes the AUC-Dose relationship as: change in AUC =
      0.02063 * dose change. The model suggests that dose changes in the range of 145
      727 mg/m2 would be sufficient to adjust the AUC to a potential therapeutic
      threshold of >20 mg . h/L for most patients. CONCLUSIONS: 5-FU is an ideal
      candidate for PK dose optimization. Because individual factors other than dose
      change may also affect the change in AUC, longitudinal PK monitoring in all
      cycles and dose adjustment to ensure AUC in the desired range of 20-30 mg . h/L
      are recommended.

PMID- 22382461
TI  - On the emerging role of rabbit as human disease model and the instrumental role
      of novel transgenic tools.
AB  - The laboratory rabbit (Oryctolagus cuniculus) is widely used as a model for human
      diseases, because of its size, which permits non-lethal monitoring of
      physiological changes and similar disease characteristics. Novel transgenic tools
      such as, the zinc finger nuclease method and the sleeping beauty transposon
      mediated or BAC transgenesis were recently adapted to the laboratory rabbit and
      opened new opportunities in precise tissue and developmental stage specific gene
      expression/silencing, coupled with increased transgenic efficiencies. Many facets
      of human development and diseases cannot be investigated in rodents. This is
      especially true for early prenatal development, its long-lasting effects on
      health and complex disorders, and some economically important diseases such as
      atherosclerosis or cardiovascular diseases. The first transgenic rabbits models
      of arrhythmogenesis mimic human cardiac diseases much better than transgenic mice
      and hereby underline the importance of non-mouse models. Another emerging field
      is epigenetic reprogramming and pathogenic mechanisms in diabetic pregnancy,
      where rabbit models are indispensable. Beyond that rabbit is used for decades as
      major source of polyclonal antibodies and recently in monoclonal antibody
      production. Alteration of its genome to increase the efficiency and value of the
      antibodies by humanization of the immunoglobulin genes, or by increasing the
      expression of a special receptor (Fc receptor) that augments humoral immune
      response is a current demand.

PMID- 22382462
TI  - Genetic transformation of fruit trees: current status and remaining challenges.
AB  - Genetic transformation has emerged as a powerful tool for genetic improvement of
      fruit trees hindered by their reproductive biology and their high levels of
      heterozygosity. For years, genetic engineering of fruit trees has focussed
      principally on enhancing disease resistance (against viruses, fungi, and
      bacteria), although there are few examples of field cultivation and commercial
      application of these transgenic plants. In addition, over the years much work has
      been performed to enhance abiotic stress tolerance, to induce modifications of
      plant growth and habit, to produce marker-free transgenic plants and to improve
      fruit quality by modification of genes that are crucially important in the
      production of specific plant components. Recently, with the release of several
      genome sequences, studies of functional genomics are becoming increasingly
      important: by modification (overexpression or silencing) of genes involved in the
      production of specific plant components is possible to uncover regulatory
      mechanisms associated with the biosynthesis and catabolism of metabolites in
      plants. This review focuses on the main advances, in recent years, in genetic
      transformation of the most important species of fruit trees, devoting particular
      attention to functional genomics approaches and possible future challenges of
      genetic engineering for these species in the post-genomic era.

PMID- 22382463
TI  - Purification of the therapeutic antibody trastuzumab from genetically modified
      plants using safflower Protein A-oleosin oilbody technology.
AB  - Production of therapeutic monoclonal antibodies using genetically modified plants
      may provide low cost, high scalability and product safety; however, antibody
      purification from plants presents a challenge due to the large quantities of
      biomass that need to be processed. Protein A column chromatography is widely used
      in the pharmaceutical industry for antibody purification, but its application is
      limited by cost, scalability and column fouling problems when purifying plant
      derived antibodies. Protein A-oleosin oilbodies (Protein A-OB), expressed in
      transgenic safflower seeds, are relatively inexpensive to produce and provide a
      new approach for the capture of monoclonal antibodies from plants. When Protein A
      OB is mixed with crude extracts from plants engineered to express therapeutic
      antibodies, the Protein A-OB captures the antibody in the oilbody phase while
      impurities remain in the aqueous phase. This is followed by repeated partitioning
      of oilbody phase against an aqueous phase via centrifugation to remove impurities
      before purified antibody is eluted from the oilbodies. We have developed this
      purification process to recover trastuzumab, an anti-HER2 monoclonal antibody
      used for therapy against specific breast-cancers that over express HER2 (human
      epidermal growth factor receptor 2), from transiently infected Nicotiana
      benthamiana. Protein A-OB overcomes the fouling problem associated with
      traditional Protein A chromatography, allowing for the development of an
      inexpensive, scalable and novel high-resolution method for the capture of
      antibodies based on simple mixing and phase separation.

PMID- 22382464
TI  - Karyopathological traits of thyrocytes and exposure to radioiodines in Belarusian
      children and adolescents following the accident at the Chernobyl nuclear power
      plant.
AB  - The Belarus-American (BelAm) thyroid study cohort consists of persons who were 0
      18 years of age at the time of exposure to radioactive iodine fallout from the
      1986 Chernobyl nuclear power plant accident and who have undergone serial thyroid
      screenings with referral for fine-needle aspiration biopsy (FNAB) using
      standardized criteria. We investigated thyrocyte nuclear abnormalities in
      cytological samples from FNABs in 75 BelAm subjects with single and multiple
      thyroid nodules and 47 nodular goiter patients from Leningrad, Russia, unexposed
      to Chernobyl fallout. Nuclear abnormalities examined included internuclear
      chromosome bridges and derivative nuclei with broken bridges (i.e., "tailed"
      nuclei), which are formed from dicentric and ring chromosomes and thus may be
      cellular markers of radiation exposure. Among subjects with single-nodular
      goiter, thyrocytes with bridges were present in 86.8% of the exposed BelAm cohort
      compared with 27.0% of unexposed controls. The average frequency of thyrocytes
      with bridges and with tailed nuclei was also significantly higher in the BelAm
      subjects than in controls. Among subjects with multinodular goiters, thyrocytes
      with bridges were present in 75.7% of exposed BelAm patients compared with 16.7%
      of unexposed controls; thyrocytes with tailed nuclei were observed in all of the
      BelAm subjects but in only 40% of controls, and the mean frequencies of bridges
      and tailed nuclei were significantly higher in the exposed group. Unusually, long
      bridges were detected in 29% of BelAm patients with single-nodular goiters and
      35% of those with multinodular goiters, while no such abnormalities were observed
      among patients from the Leningrad region. In the exposed subjects from BelAm, we
      also found positive correlations between their estimated dose of Iodine-131 from
      Chernobyl fallout and the frequency of tailed nuclei (p = 0.008) and bridges (p =
      0.09). Further study is needed to confirm that these phenomena represent
      consequences of radiation exposure in the human organism.

PMID- 22382465
TI  - Calcium manganese(IV) oxides: biomimetic and efficient catalysts for water
      oxidation.
AB  - CaMnO(3) and Ca(2)Mn(3)O(8) were synthesized and characterized by SEM, XRD, FTIR
      and BET. Both oxides showed oxygen evolution activity in the presence of oxone,
      cerium(IV) ammonium nitrate and H(2)O(2). Oxygen evolution from water during
      irradiation with visible light (lambda > 400 nm) was also observed upon adding
      these manganese oxides to an aqueous solution containing tris(2,2'-bipyridyl)
      ruthenium(II), as photosensitizer, and chloro pentaammine cobalt(III) chloride,
      as electron acceptor, in an acetate buffer. The amounts of dissolved manganese
      and calcium from CaMnO(3) and Ca(2)Mn(3)O(8) in the oxygen evolving reactions
      were reported and compared with other (calcium) manganese oxides. Proposed
      mechanisms of oxygen evolution and proposed roles for the calcium ions are also
      considered.

PMID- 22382467
TI  - Urological anomalies and chronic kidney disease in children with anorectal
      malformations.
AB  - BACKGROUND: This study aims to predict risk factors for urological anomalies in
      children with anorectal malformations (ARM) and describes the clinical features
      of patients who have developed chronic kidney disease. METHODS: We
      retrospectively reviewed infants with ARM who received surgery and were followed
      at the Sabah Women and Children's Hospital, Malaysia, from 1986 to 2010. RESULTS:
      One hundred and twenty-two children with anorectal malformations were studied,
      after excluding 24 children with incomplete data. Three factors were significant
      as predictors of the presence of a urological anomaly: high ARM lesion (OR 3.12,
      95%CI 1.1-8.9), the presence of genital abnormality (OR 2.95, 95%CI 1.10-7.91)
      and cloacal anomaly in girls (OR 8.27, 95% CI 1.91-35.6). The most common
      anomalies were vesicoureteric reflux, single kidney and neurogenic bladder.
      Chronic kidney disease (CKD) was noted in 5.7%, in children who had recurrent
      urinary tract infections, neurogenic bladder or complex renal tract pathology;
      end-stage renal failure was seen in only 0.8% of children with ARM. CONCLUSION:
      Urological anomalies were seen in 23% of patients, but the overall incidence of
      CKD and end-stage renal disease is low. Early identification of infants with ARM
      at risk of renal failure may be important for renal survival.

PMID- 22382466
TI  - Buffer-dependent regulation of aquaporin-1 expression and function in human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Biocompatible peritoneal dialysis fluids (PDF) are buffered with
      lactate and/or bicarbonate. We hypothesized that the reduced toxicity of the
      biocompatible solutions might unmask specific effects of the buffer type on
      mesothelial cell functions. METHODS: Human peritoneal mesothelial cells (HPMC)
      were incubated with bicarbonate (B-)PDF or lactate-buffered (L-)PDF followed by
      messenger RNA (mRNA) and protein analysis. Gene silencing was achieved using
      small interfering RNA (siRNA), functional studies using Transwell culture
      systems, and monolayer wound-healing assays. RESULTS: Incubation with B-PDF
      increased HPMC migration in the Transwell and monolayer wound-healing assay to
      245 +/- 99 and 137 +/- 11% compared with L-PDF. Gene silencing showed this effect
      to be entirely dependent on the expression of aquaporin-1 (AQP-1) and independent
      of AQP-3. Exposure of HPMC to B-PDF increased AQP-1 mRNA and protein abundance to
      209  +/- 80 and 197  +/-  60% of medium control; the effect was pH dependent. L
      PDF reduced AQP-1 mRNA. Addition of bicarbonate to L-PDF increased AQP-1
      abundance by threefold; mRNA half-life remained unchanged. Immunocytochemistry
      confirmed opposite changes of AQP-1 cell-membrane abundance with B-PDF and L-PDF.
      CONCLUSIONS: Peritoneal mesothelial AQP-1 abundance and migration capacity is
      regulated by pH and buffer agents used in PD solutions. In vivo studies are
      required to delineate the impact with respect to long-term peritoneal membrane
      integrity and function.

PMID- 22382468
TI  - Synergy between oxacillin and manuka honey sensitizes methicillin-resistant
      Staphylococcus aureus to oxacillin.
AB  - OBJECTIVES: Honey is an ancient wound remedy that has recently been introduced
      into modern clinical practice in developed countries. Manuka honey inhibits
      growth of methicillin-resistant Staphylococcus aureus (MRSA) by preventing cell
      division. In Gram-negative bacteria a synergistic interaction between honey and
      antibiotics has been suggested. We aimed to determine the effect of manuka honey
      on oxacillin resistance in MRSA. METHODS: Inhibition of MRSA by manuka honey and
      oxacillin separately and in combination was tested by disc diffusion, Etest
      strips, serial broth dilution, chequerboards and growth curves. RESULTS: Manuka
      honey and oxacillin interacted synergistically to inhibit MRSA. Manuka honey
      reversed oxacillin resistance in MRSA, and down-regulation of mecR1 was found in
      cells treated with manuka honey. CONCLUSIONS: Microarray analysis showed that
      exposure of MRSA to inhibitory concentrations of manuka honey resulted in down
      regulation of mecR1. Here we demonstrated that subinhibitory concentrations of
      honey in combination with oxacillin restored oxacillin susceptibility to MRSA.
      Other honey and antibiotic combinations must now be evaluated.

PMID- 22382469
TI  - Occurrence and characteristics of extended-spectrum-beta-lactamase- and AmpC
      producing clinical isolates derived from companion animals and horses.
AB  - OBJECTIVES: To investigate the occurrence and characteristics of extended
      spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae isolates in
      clinical samples of companion animals and horses and compare the results with
      ESBL/AmpC-producing isolates described in humans. METHODS: Between October 2007
      and August 2009, 2700 Enterobacteriaceae derived from clinical infections in
      companion animals and horses were collected. Isolates displaying inhibition zones
      of <= 25 mm for ceftiofur and/or cefquinome by disc diffusion were included.
      ESBL/AmpC production was confirmed by combination disc tests. The presence of
      resistance genes was identified by microarray, PCR and sequencing, Escherichia
      coli genotypes by multilocus sequence typing and antimicrobial susceptibility by
      broth microdilution. RESULTS: Sixty-five isolates from dogs (n = 38), cats (n =
      14), horses (n = 12) and a turtle were included. Six Enterobacteriaceae species
      were observed, mostly derived from urinary tract infections (n = 32). All except
      10 isolates tested resistant to cefotaxime and ceftazidime by broth microdilution
      using clinical breakpoints. ESBL/AmpC genes observed were bla(CTX-M-1, -2, -9, 
      14, -15,) bla(TEM-52), bla(CMY-2) and bla(CMY-)(39). bla(CTX-M-1) was predominant
      (n = 17). bla(CTX-M-9) occurred in combination with qnrA1 in 3 of the 11
      Enterobacter cloacae isolates. Twenty-eight different E. coli sequence types
      (STs) were found. E. coli carrying bla(CTX-M-1) belonged to 13 STs of which 3
      were previously described in Dutch poultry and patients. CONCLUSIONS: This is the
      first study among a large collection of Dutch companion animals and horses
      characterizing ESBL/AmpC-producing isolates. A similarity in resistance genes and
      E. coli STs among these isolates and isolates from Dutch poultry and humans may
      suggest exchange of resistance between different reservoirs.

PMID- 22382470
TI  - Prevalence of subtype-related polymorphisms associated with in vitro resistance
      to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients.
AB  - OBJECTIVES: BMS-626529 is a member of the new drug class of HIV-1 attachment
      inhibitors currently in development. Mutations selected during in vitro
      experiments with BMS-626529 are located in the gp120 region: L116P, A204D, M426L,
      M434I-V506M and M475I. A differential antiviral activity of BMS-626529 was
      observed depending of the viral subtype. The aim of our study was to assess the
      prevalence of subtype-related polymorphisms previously described as being
      associated with in vitro resistance to BMS-626529 in patients infected with
      different HIV-1 'non-B' subtypes. PATIENTS AND METHODS: The prevalence of
      substitutions in gp120 was assessed in 85 HIV-infected patients (not previously
      treated with attachment inhibitors and infected with HIV-1 'non-B' subtypes) by
      performing direct sequencing of the gp120 region. RESULTS: The most prevalent HIV
      1 subtype was CRF02_AG (n = 46, 54%). The M426L substitution was found in virus
      from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. The M434I
      substitution was found in virus from 11 patients (12.9%), mainly in subtypes
      CRF02_AG and CRF06_cpx. None of the CRF02_AG viruses harboured both M426L and
      M434I substitutions. CONCLUSIONS: In our series, the M426L substitution in the
      gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples,
      respectively, and might affect the activity of BMS-626529 against these specific
      subtypes. Further studies are needed to better describe associations between HIV
      1 'non-B'-subtype-related polymorphism profiles and the level of phenotypic
      resistance to attachment inhibitor BMS-626529.

PMID- 22382471
TI  - Altered vancomycin pharmacokinetics in obese and morbidly obese patients: what we
      have learned over the past 30 years.
AB  - Vancomycin was the first glycopeptide antibiotic introduced into clinical
      practice. Despite the numerous benefits of vancomycin, clinicians have struggled
      to dose vancomycin successfully in obese patients to achieve a therapeutic
      concentration for optimal bacterial killing. Owing to the hydrophilicity of
      vancomycin and the increase in both adipose tissue and muscle mass associated
      with obesity, the volume of distribution of vancomycin in obese patients is
      likely to be altered compared with non-obese patients. In addition to an increase
      in body mass, obesity is associated with an increase in certain circulating
      proteins, which results in altered free serum vancomycin concentration. Another
      alteration that occurs in obesity is increased blood flow secondary to increased
      cardiac output and blood volume, resulting in increased vancomycin clearance in
      obese patients. Vancomycin pharmacokinetics in the obese population remain an
      area of much debate, one that requires continued research given the rising number
      of obese patients in both the USA and worldwide.

PMID- 22382472
TI  - FDA approves glaucoma treatment.

PMID- 22382473
TI  - Drug shortages undergo more scrutiny by Congress.

PMID- 22382474
TI  - Non-U.S. pharmacists face residency hurdles.

PMID- 22382475
TI  - Information extraction from narrative data.

PMID- 22382476
TI  - Overcoming barriers to scholarly activity in a clinical practice setting.

PMID- 22382477
TI  - Preventing venous thromboembolism in hospitalized patients with cancer: improving
      compliance with clinical practice guidelines.
AB  - PURPOSE: The use of anticoagulants for the prevention of venous thromboembolism
      (VTE) in hospitalized medical and surgical oncology patients is discussed.
      SUMMARY: Hospitalized patients are often at risk for developing VTE, and risk is
      increased in patients who have cancer. Moreover, the incidence of VTE appears to
      be rising in hospitalized cancer patients, who have a 2.2-fold increased risk of
      mortality with a VTE compared with similar patients without VTE. The literature
      indicates that these patients are often inadequately anticoagulated, despite
      strong recommendations for prophylaxis. Although there are few studies that
      specifically address VTE prophylaxis in cancer patients, there are several large
      trials that have examined data in cancer subgroups. The trials have directly
      compared low-molecular-weight heparin (LMWH) with placebo, unfractionated heparin
      with LMWH, factor Xa inhibitor (fondaparinux) with placebo, and fondaparinux with
      LMWH. Three important guidelines provide current recommendations for VTE
      prophylaxis; the American Society of Clinical Oncology (ASCO), the National
      Comprehensive Cancer Network (NCCN), and the American College of Chest Physicians
      (ACCP) recommend unfractionated heparin, LMWH, or fondaparinux for VTE
      prophylaxis when there are no contraindications. Pharmacists can play an
      essential role in ensuring that VTE prophylaxis is appropriate for individual
      patients. Interventions to improve compliance with guidelines are particularly
      important now due to financial incentives from quality-focused organizations
      whose mandate is to decrease preventable mortality events in hospitals.
      CONCLUSION: Hospitalized patients with cancer often do not receive appropriate
      thromboprophylaxis. Guidelines from ASCO, ACCP, and NCCN recommend unfractionated
      heparin, an LMWH, or fondaparinux for VTE prophylaxis when there are no
      contraindications to such therapy.

PMID- 22382478
TI  - The role of mucoregulatory agents after continence-preserving urinary diversion
      surgery.
AB  - PURPOSE: The postsurgical use of N-acetylcysteine, octreotide, and other agents
      to reduce mucus accumulation after urinary diversion procedures is described.
      SUMMARY: Patients undergoing continence-sparing bladder resection are at risk for
      infection and stone formation due to mucus accumulation. In addition to N
      acetylcysteine, agents studied for mucoregulatory control in such patients
      include aspirin, urea, ranitidine, and octreotide. N-acetylcysteine has high
      mucolytic activity in vitro, and positive outcomes with instillations of 20% N
      acetylcysteine solution have been reported in some patients. Significant mucus
      reductions were reported in small numbers of patients treated with oral
      ranitidine 300 mg daily or instillations of 30 mL of urea 40% solution, while the
      benefits of aspirin are more questionable. To date, there has been only one
      randomized controlled trial comparing various agents for mucus reduction after
      reconstructive bladder surgery; the results indicated no significant benefits
      with the use of N-acetylcysteine, aspirin, or ranitidine. In one small study (n =
      40), the use of subcutaneous octreotide immediately before and for 15 days after
      surgery was reported to yield significant reductions in mucus production, the
      need for bladder irrigation to clear blockages, and the mean duration of hospital
      stays. CONCLUSION: Various agents evaluated for mucus control after urinary
      diversion procedures (oral ranitidine or aspirin, N-acetylcysteine or urea
      instillations, and subcutaneous octreotide), while reportedly effective for some
      patients, remain of questionable benefit. More research is needed to define the
      optimal role of these agents for this indication.

PMID- 22382479
TI  - High-dose argatroban for treatment of heparin-induced thrombocytopenia with
      thrombosis: a case report and review of laboratory considerations.
AB  - PURPOSE: A case report describing high-dose argatroban for the treatment of
      heparin-induced thrombocytopenia (HIT) with thrombosis and associated
      considerations in interpreting laboratory monitoring data are presented. SUMMARY:
      A 51-year-old woman with an extensive history of coronary artery disease arrived
      at the emergency department with complaints of chest pain. The patient was
      admitted, and coronary artery bypass graft surgery was ultimately performed. The
      patient had a baseline platelet count of 177,000 cells/MUL. During
      hospitalization, the patient received heparin, and her platelet count dropped to
      12,000 cells/MUL 13 days after the initiation of heparin. The patient developed
      swelling around a peripherally inserted central catheter and later developed deep
      vein thrombosis. An argatroban infusion of 2 MUg/kg/min was initiated, with a
      target activated partial thromboplastin time (aPTT) of 40-80 seconds. After 5
      days of therapy, the patient had increased swelling in her right arm and an aPTT
      of 56 seconds. Her goal aPTT was subsequently increased. Six days later, the
      patient developed a left-lower-extremity DVT despite aPTTs within the goal range.
      A new aPTT target of >75 seconds was set. The infusion rate was increased to 15.5
      MUg/kg/min to attain the target aPTT. Results of an in vitro test led to an
      alternative interpretation of aPTT and International Normalized Ratio values that
      aided in the monitoring of argatroban during the high-dose infusion. CONCLUSION:
      A patient with HIT with thrombosis was successfully treated with unusually high
      dosages of argatroban and may have had serum argatroban concentrations exceeding
      what has commonly been thought to be the therapeutic range.

PMID- 22382480
TI  - Mirtazapine and mefloquine therapy for progressive multifocal leukoencephalopathy
      in a patient infected with human immunodeficiency virus.
AB  - PURPOSE: A case of progressive multifocal leukoencephalopathy (PML) in a patient
      infected with human immunodeficiency virus (HIV) treated with mirtazapine and
      mefloquine is reported. SUMMARY: A 49-year-old African-American man who was
      recently diagnosed with HIV infection was admitted to the hospital for
      progressive ataxia, dysarthria, and unsteady gait. Upon initial examination, the
      patient was fully oriented but appeared drowsy and uncooperative and was observed
      to be unsteady on his feet. Magnetic resonance imaging of the patient's brain
      revealed marked cerebellar and mild cerebral atrophy and moderate, nonspecific
      white matter disease. The results of a lumbar puncture revealed the presence of
      JC virus, and PML was diagnosed. As the patient's cognitive function began to
      worsen, mirtazapine and mefloquine were initiated. Treatment with mirtazapine 30
      mg orally daily and mefloquine hydrochloride 250 mg orally for three days, then
      250 mg weekly, was initiated. The dosing regimen was derived from a study
      currently underway at Washington University in St. Louis, Missouri. The patient
      also had pneumonia and, on day 7 of hospitalization, required intubation. The
      patient was extubated on day 11 and showed significant cognitive improvement; he
      was able to communicate his wish to enact a "Do Not Intubate" order. At this
      time, the patient began refusing all medications and ultimately died on hospital
      day 16 due to respiratory failure. CONCLUSION: A patient with HIV infection and
      PML was treated with mirtazapine and mefloquine. He tolerated the drugs well and
      exhibited functional and cognitive improvement, but the specific effects of
      mirtazapine and mefloquine were difficult to discern.

PMID- 22382481
TI  - Successful desensitization to docetaxel after severe hypersensitivity reactions
      in two patients.
AB  - PURPOSE: Two cases of successful desensitization to docetaxel after severe
      hypersensitivity reactions are reported. SUMMARY: Two patients with gynecological
      malignancies (uterine leiomyosarcoma and ovarian adenocarcinoma) experienced
      severe hypersensitivity reactions with docetaxel, including flushing, numbness,
      sharp radiating pain, severe nausea and vomiting, apnea, and unresponsiveness.
      Both patients received ondansetron before docetaxel. One patient received
      dexamethasone, diphenhydramine, and famotidine premedication before docetaxel, as
      she had previously reacted to paclitaxel. Docetaxel infusions were stopped, and
      the reactions were treated with diphenhydramine and dexamethasone (one patient
      also received famotidine). After resolution of symptoms, the docetaxel was not
      reinitiated due to the nature of the reactions. For the next cycle, both patients
      received a graded drug challenge or desensitization. Both were pre-medicated with
      dexamethasone, diphenhydramine, and famotidine. The docetaxel was given as
      infusions of 0.1%, 1%, and 10% of the dose, with each infusion given over one
      hour. After this, the remainder of the dose was infused over one hour. Both
      patients tolerated this desensitization well and completed a total of three and
      four cycles each. The first patient to receive the desensitization did complain
      of chest pain during the first desensitization, and the infusion rate was
      decreased to administer the drug over two hours. After she tolerated two cycles
      of two-hour infusions, the infusion rate was increased to administer each
      docetaxel infusion over one hour. CONCLUSION: Two patients who had severe
      hypersensitivity reactions to docetaxel successfully received further docetaxel
      doses via a desensitization procedure that involved the sequential administration
      of solutions containing increasing concentrations of the drug.

PMID- 22382482
TI  - Impact of a pharmacist-directed intervention in postmenopausal women after
      fracture.
AB  - PURPOSE: The impact of decentralized clinical pharmacy services on the
      implementation of appropriate care in postmenopausal women with a recent history
      of a fracture was assessed. METHODS: Women 67 years of age or older with a
      documented fracture between January 1 and December 31, 2007, were identified in
      two geographic regions. At the intervention site, a decentralized clinical
      pharmacy-based osteoporosis management service (CPOMS) intervened on
      postmenopausal women following fracture, while the comparison group utilized a
      centralized registered nurse to manage this population. In both groups,
      interventions included initiation of either osteoporosis medication or bone
      mineral density (BMD) screening. RESULTS: Of the 827 women in the CPOMS group,
      65% (523) initiated a medication for osteoporosis or completed BMD screening
      within 6 months of the fracture, compared with 46% (139) of the 302 women in the
      comparison group (p < 0.001; cumulative incidence ratio [CIR], 1.75; 95%
      confidence interval [CI], 1.44-2.12). CPOMS patients were nearly twice as likely
      as comparison group patients to purchase osteoporotic medications (42% [347 of
      827] versus 24% [73 of 302]; CIR, 1.89; 95% CI, 1.50-2.40) and equally likely to
      undergo BMD testing (35% [289 of 827] versus 31% [94 of 302]; CIR, 1.13; 95% CI,
      0.91-1.39). Both interventions achieved results substantially higher than
      national averages. Of patients receiving a medication and continuous membership
      for 12 months, adherence was also significantly higher in the CPOMS group (46%
      [39 of 291] versus 28% [20 of 71], respectively; p = 0.007). CONCLUSION: An
      integrated pharmacist-run osteoporosis management service demonstrated a
      substantial increase in the rate of osteoporosis drug initiation among post
      menopausal women who experienced a fracture compared with a centrally located
      nurse-run service. BMD screening rates did not significantly differ between
      groups.

PMID- 22382483
TI  - Effect of a patient support program on access to oral therapy for hematologic
      malignancies.
AB  - PURPOSE: The results of a study assessing the effectiveness of a manufacturer
      sponsored assistance program for patients prescribed oral cancer therapies are
      presented. METHODS: Rates of dispensing success were evaluated in a random sample
      of patients (n = 1000) who enrolled in the Celgene Patient Support (CPS) program
      for assistance obtaining lenalidomide or thalidomide over a two-year period and a
      control group of patients (n = 1000) who registered to receive the drugs under
      restricted-distribution protocols but did not receive CPS assistance. The main
      study outcomes were (1) the proportion of patients who actually received
      medication and (2) the time from prescription approval to the initial dispensing
      of medication. RESULTS: Despite the complex access issues faced by program
      enrollees, the proportion of CPS participants who received medication (89%) was
      comparable to the proportion of patients who received medication in the control
      cohort (91%). The median time from the approval of prescriptions to the initial
      dispensing of medication was also comparable in the CPS and control groups (eight
      days versus five days). The study also evaluated the reasons why medication was
      not dispensed to CPS enrollees in some cases. CONCLUSION: The percentage of
      patients who were dispensed prescriptions for lenalidomide or thalidomide did not
      differ significantly between those who were enrolled in a patient assistance
      program and those who were not. The median time between prescription
      authorization and first dispensing was comparable among program and nonprogram
      patients.

PMID- 22382484
TI  - Pharmacist's role in a Parkinson's disease and movement disorders clinic.
AB  - PURPOSE: The expanding role of a clinical pharmacist at a Veterans Affairs (VA)
      out-patient clinic for patients with Parkinson's disease (PD) and movement
      disorders is described. SUMMARY: San Francisco VA Medical Center added a clinical
      pharmacist to the multi-disciplinary team serving patients at an outpatient
      clinic operated by its Parkinson's Disease Research, Education and Clinical
      Center (PADRECC). During the first six months after joining the clinic team, the
      pharmacist met with 131 patients and made a total of 69 drug therapy
      recommendations that were implemented by neurologists, clinical nurse
      specialists, and other PADRECC providers. The results of a retrospective chart
      review suggested that in about 21% of the cases evaluated, the pharmacist's
      recommendations contributed to an improved medical outcome or the resolution of a
      medical problem. Anonymous surveys indicated that clinic providers (n = 33) and
      patients (n = 20) were satisfied with the pharmacist's services. Using a five
      point Likert scale (scores ranged from 1 for "strongly disagree" to 5 for
      "strongly agree") that they had more time to devote to other clinic
      responsibilities with the pharmacist present in the clinic (mean score, 4.79);
      patients indicated that they had an improved understanding of their medications
      after speaking with the pharmacist (mean score, 4.88). CONCLUSION: A clinical
      pharmacist's regular involvement in an outpatient PD and movement disorders
      clinic has been well received by patients and clinic providers. The study results
      suggest that the pharmacist has made important contributions in areas such as
      therapeutic problem solving and medication education while freeing up providers
      for other responsibilities.

PMID- 22382485
TI  - Implementation of continuous infusion of blood coagulation factors at an academic
      medical center.
AB  - PURPOSE: A multidisciplinary initiative to promote more cost-effective use of
      blood factor derivatives and increase pharmacist involvement in associated order
      verification, dispensing, and monitoring activities is described. SUMMARY: After
      an evaluation of a hospital's procedures for the use of blood factor derivatives
      identified inconsistencies and opportunities for cost savings, a revised
      medication-use process promoting continuous infusion of selected products
      (factors VIII, IX, and VIII/von Willebrand factor) was developed by pharmacy
      staff with input from physicians and nurse educators. The implementation of the
      enhanced medication-use procedures included (1) the publication of a compendium
      of key information on commonly used blood factors, including specific guidance on
      dosing and administration, (2) the use of Web-based educational modules targeting
      pharmacists and nurses, (3) greater involvement by pharmacists in blood factor
      order justification and verification, (4) routine pharmacist assessment of
      pertinent laboratory values and other determinants of optimal dosing, and (5)
      refined procedures for changing i.v. tubing. Surveys of pharmacists conducted
      before and after the practice changes indicated a significant increase in their
      knowledge of blood factor products and evidence-based best practices for the
      management of hemophilia. CONCLUSION: Through a multidisciplinary initiative
      involving pharmacists, physicians, and nurses, new procedures to promote
      continuous infusion of selected blood factor products were implemented. Results
      of a postimplementation survey indicated that educational tools were effective in
      increasing pharmacists' knowledge of blood factor derivatives and hemophilia
      management.

PMID- 22382486
TI  - Small non-coding RNAs govern mammary gland tumorigenesis.
AB  - Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of
      miRNAs in the regulation of mammary gland tumorigenesis has been widely studied
      while the role for other small non-coding RNAs remains unclear. Here we summarize
      the involvement of miRNA in breast cancer onset and progression through
      regulating the cell cycle and cellular proliferation. The regulation of breast
      cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the
      emerging evidence demonstrating the involvement of piRNA and snoRNA in breast
      cancer is briefly described.

PMID- 22382487
TI  - Exploiting comparative mapping among Brassica species to accelerate the physical
      delimitation of a genic male-sterile locus (BnRf) in Brassica napus.
AB  - The recessive genic male sterility (RGMS) line 9012AB has been used as an
      important pollination control system for rapeseed hybrid production in China.
      Here, we report our study on physical mapping of one male-sterile locus (BnRf) in
      9012AB by exploiting the comparative genomics among Brassica species. The genetic
      maps around BnRf from previous reports were integrated and enriched with markers
      from the Brassica A7 chromosome. Subsequent collinearity analysis of these
      markers contributed to the identification of a novel ancestral karyotype block F
      that possibly encompasses BnRf. Fourteen insertion/deletion markers were further
      developed from this conserved block and genotyped in three large backcross
      populations, leading to the construction of high-resolution local genetic maps
      where the BnRf locus was restricted to a less than 0.1-cM region. Moreover, it
      was observed that the target region in Brassica napus shares a high collinearity
      relationship with a region from the Brassica rapa A7 chromosome. A BnRf
      cosegregated marker (AT3G23870) was then used to screen a B. napus bacterial
      artificial chromosome (BAC) library. From the resulting 16 positive BAC clones,
      one (JBnB089D05) was identified to most possibly contain the BnRf (c) allele.
      With the assistance of the genome sequence from the Brassica rapa homolog, the
      13.8-kb DNA fragment covering both closest flanking markers from the BAC clone
      was isolated. Gene annotation based on the comparison of microcollinear regions
      among Brassica napus, B. rapa and Arabidopsis showed that five potential open
      reading frames reside in this fragment. These results provide a foundation for
      the characterization of the BnRf locus and allow a better understanding of the
      chromosome evolution around BnRf.

PMID- 22382488
TI  - Map-based cloning of a recessive genic male sterility locus in Brassica napus L.
      and development of its functional marker.
AB  - We previously mapped one male-sterile gene (Bnms3) from an extensively used
      recessive genic male sterility line (9012AB) in Brassica napus to a 0.14-cM
      genomic region. In this study, two highly homologous BAC contigs possibly
      containing the candidate BnMs3 gene were identified using a map-based cloning
      strategy. A BnMs3-linked SCAR marker (DM1) capable of differentiating the
      subgenomes between B. rapa and the B. oleracea aided mapping of BnMs3 on the
      contig derived from the B. napus chromosome C9. One representative BAC clone was
      sequenced from each of the two contigs and resulted in a larger number of markers
      according to the sequence difference between the two clones. To isolate BnMs3,
      these markers were then analyzed in another two BC(1) populations with different
      genetic backgrounds. This assay allowed for a delimitation of the mutated
      functional region of BnMs3 to a 9.3-kb DNA fragment. Gene prediction suggested
      that one complete open reading frame (ORF, ORF2) and partial CDS fragments of
      ORF1 and ORF3 reside in this fragment. Sequence comparison and genetic
      transformation eventually indicated that ORF1 (designated as BnaC9.Tic40), an
      analogue of the Arabidopsis gene AT5G16620 which encodes a translocon of the
      inner envelope of chloroplasts 40 (Tic40), is the only candidate gene of BnMs3.
      Furthermore, two distinct mutation types in ORF1 both causing the male-sterile
      phenotype were individually revealed from 9012A and the temporary maintainer line
      T45. The molecular mechanism of this male sterility as well as the application of
      BnMs3-associated functional and cosegregated markers in true breeding programs
      was also discussed.

PMID- 22382489
TI  - Gut check: do interactions between environmental chemicals and intestinal
      microbiota affect obesity and diabetes?

PMID- 22382490
TI  - Qualitative research: the importance of conducting research that doesn't "count".

PMID- 22382491
TI  - Use of social media in health promotion: purposes, key performance indicators,
      and evaluation metrics.
AB  - Despite the expanding use of social media, little has been published about its
      appropriate role in health promotion, and even less has been written about
      evaluation. The purpose of this article is threefold: (a) outline purposes for
      social media in health promotion, (b) identify potential key performance
      indicators associated with these purposes, and (c) propose evaluation metrics for
      social media related to the key performance indicators. Process evaluation is
      presented in this article as an overarching evaluation strategy for social media.

PMID- 22382492
TI  - Integrating social media and social marketing: a four-step process.
AB  - Social media is a group of Internet-based applications that allows individuals to
      create, collaborate, and share content with one another. Practitioners can
      realize social media's untapped potential by incorporating it as part of the
      larger social marketing strategy, beyond promotion. Social media, if used
      correctly, may help organizations increase their capacity for putting the
      consumer at the center of the social marketing process. The purpose of this
      article is to provide a template for strategic thinking to successfully include
      social media as part of the social marketing strategy by using a four-step
      process.

PMID- 22382493
TI  - Standardized patients: a promising tool for health education and health
      promotion.
AB  - Standardized patients (SPs) are trained actors who are used to engage health care
      providers in various types of clinical encounters for the purposes of training
      and evaluation. In the past, SPs have most often been a tool for training
      clinicians in "traditional" medical skills such as the taking of medical
      histories or the conduct of physical exams. More recently, however, SPs have been
      increasingly used to assist in the development and assessment of psychosocial
      skills, including those related to patient-centered communication, relationship
      building, and motivational interviewing. Given this shift, it is argued that the
      time is ripe for exploring ways that health educators can adopt SP methodologies,
      whether for providing continuing education for individual providers or evaluating
      organizations or programs. This article introduces ways of using SPs and
      discusses strengths and challenges related to various approaches.

PMID- 22382494
TI  - Quality of life of adolescents with autism spectrum disorders: comparison to
      adolescents with diabetes.
AB  - Relationships are of great importance during adolescence. Because of their
      social, communication and behavioral impairments, adolescents with Asperger's
      syndrome (AS) or high functioning autism (HFA) probably suffer from considerable
      impairment of their quality of life when facing their peers in school.
      Nevertheless, only one recent study has been published on this subject,
      indicating a lower health-related quality of life in children and adolescents
      with autism spectrum disorders (ASD) than in healthy controls. The goals of our
      study were to clarify the consequences of autistic disorder without mental
      retardation on such adolescents' daily lives, and to consider them in comparison
      with the impact of a chronic somatic disease (diabetes) and with the period of
      adolescence itself, using the VSP-A questionnaire. Adolescents with diabetes were
      chosen as a comparison group because of the encumbrance of having a constant need
      for insulin supplementation, to be assimilated to the constant need for
      communicative adjustments in teenagers with ASD, and the consequences in daily
      life. The effects of social skill training and social support on quality of life
      and the appropriateness of using the VSP-A in this population were also studied.
      Twenty-six adolescents with AS and HFA, 44 diabetic adolescents, and 250 controls
      completed a self-administered and validated questionnaire on quality of life, the
      VSP-A. Scores for adolescents with ASD were significantly lower than those of the
      control and the diabetic adolescents, especially for friendships, leisure time,
      and affective and sexual relationships. On the other hand, better scores were
      obtained for the relationships with parents and teachers and for self-image.
      Social parameters affected the quality of life of subjects with ASD, such as
      having friends, regularly participating in a sport, and having the support of a
      school carer. For subjects with autistic spectrum disorders and without mental
      retardation, impairment of quality of life is significant in adolescence and
      young adulthood. Such adolescents are dissatisfied with their relationships,
      although they often have real motivation to succeed with them. Relevance of VSP-A
      questionnaire in these special individuals is discussed.

PMID- 22382495
TI  - Life before birth: are the dice tossed for the rest of our lives?

PMID- 22382496
TI  - MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of
      multiple genes from the non-canonical TGF-beta signalling pathway.
AB  - Transforming growth factor-beta (TGF-beta) signaling regulates many diverse
      cellular activities through both canonical (SMAD-dependent) and non-canonical
      branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like
      guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we
      demonstrate that miR-335 directly targets and downregulates genes in the TGF-beta
      non-canonical pathways, including the Rho-associated coiled-coil containing
      protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream
      pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces
      phosphorylation levels of the motor protein myosin light chain (MLC) leading to a
      significant inhibition of the invasive and migratory potential of neuroblastoma
      cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1
      (LRG1) messenger RNA, which similarly results in a significant reduction in the
      phosphorylation status of MLC and a decrease in neuroblastoma cell migration and
      invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its
      activity presumably by exerting its effect within the non-canonical TGF-beta
      pathway. Moreover, we demonstrate that the MYCN transcription factor, whose
      coding sequence is highly amplified in a particularly clinically aggressive
      neuroblastoma tumor subtype, directly binds to a region immediately upstream of
      the miR-335 transcriptional start site, resulting in transcriptional repression.
      We conclude that MYCN contributes to neuroblastoma cell migration and invasion,
      by directly downregulating miR-335, resulting in the upregulation of the TGF-beta
      signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively
      promote this process. Our results provide novel insight into the direct
      regulation of TGF-beta non-canonical signaling by miR-335, which in turn is
      downregulated by MYCN.

PMID- 22382497
TI  - Lung cancer and DNA repair genes: multilevel association analysis from the
      International Lung Cancer Consortium.
AB  - Lung cancer (LC) is the leading cause of cancer-related death worldwide and
      tobacco smoking is the major associated risk factor. DNA repair is an important
      process, maintaining genome integrity and polymorphisms in DNA repair genes may
      contribute to susceptibility to LC. To explore the role of DNA repair genes in
      LC, we conducted a multilevel association study with 1655 single nucleotide
      polymorphisms (SNPs) in 211 DNA repair genes using 6911 individuals pooled from
      four genome-wide case-control studies. Single SNP association corroborates
      previous reports of association with rs3131379, located on the gene MSH5 (P =
      3.57 * 10-5) and returns a similar risk estimate. The effect of this SNP is
      modulated by histological subtype. On the log-additive scale, the odds ratio per
      allele is 1.04 (0.84-1.30) for adenocarcinomas, 1.52 (1.28-1.80) for squamous
      cell carcinomas and 1.31 (1.09-1.57) for other histologies (heterogeneity test: P
      = 9.1 * 10(-)(3)). Gene-based association analysis identifies three repair genes
      associated with LC (P < 0.01): UBE2N, structural maintenance of chromosomes 1L2
      and POLB. Two additional genes (RAD52 and POLN) are borderline significant.
      Pathway-based association analysis identifies five repair pathways associated
      with LC (P < 0.01): chromatin structure, DNA polymerases, homologous
      recombination, genes involved in human diseases with sensitivity to DNA-damaging
      agents and Rad6 pathway and ubiquitination. This first international pooled
      analysis of a large dataset unravels the role of specific DNA repair pathways in
      LC and highlights the importance of accounting for gene and pathway effects when
      studying LC.

PMID- 22382498
TI  - Deciphering the molecular basis of human cardiovascular disease through network
      biology.
AB  - PURPOSE OF REVIEW: This review introduces the fundamental concepts of network
      medicine and explores the feasibility and potential impact of network-based
      methods on predicting and ameliorating individual manifestations of human
      cardiovascular disease. RECENT FINDINGS: Complex cardiovascular diseases rarely
      result from an abnormality in a single molecular effector, but, rather, nearly
      always are the net result of multiple pathobiological pathways that interact
      through an interconnected network. In the postgenomic era, a framework has
      emerged of the potential complexity of the interacting pathways that govern
      molecular actions in the human cell. As a result, network approaches have been
      developed to understand more comprehensively those interconnections that
      influence human disease. 'Network medicine' has already led to tangible
      discoveries of novel disease genes and pathways as well as improved mechanisms
      for rational drug development. SUMMARY: As methodologies evolve, network medicine
      may better capture the complexity of human pathogenesis and, thus, re-define
      personalized disease classification and therapies.

PMID- 22382499
TI  - The genetics of coronary artery disease.
AB  - PURPOSE OF REVIEW: Prevention of coronary artery disease (CAD) is an appropriate
      goal for the 21st century. Randomized clinical studies consistently show a 30-40%
      reduction in mortality and morbidity by modifying known risk factors. However,
      genetic risk, estimated to account for 40-60% of susceptibility to CAD, has until
      recently been unknown. Comprehensive prevention will require knowledge of both.
      RECENT FINDINGS: The 21st century technology has responded to the challenge.
      Whereas the first genetic risk variant was not discovered until 2007 (9p21), a
      total of 36 genetic risk factors for CAD have been discovered and verified in
      large sample sizes. A startling discovery was that over two-thirds of these
      factors do not act through known risk factors or mechanisms. This obviously has
      great implications for the pathogenesis of CAD and presents many potential
      targets for new therapy. These genetic risk factors occur more commonly in the
      population than expected, with over half of them occurring in more than 50% of
      the population, and 10 of them occurring in at least 75% of the population.
      SUMMARY: The role of genetic risk factors in genetic screening for prevention of
      heart disease is yet to be defined. The technology is already available, but
      functional analysis may be a prerequisite for their clinical application.

PMID- 22382500
TI  - The total artificial heart for biventricular heart failure and beyond.
AB  - PURPOSE OF REVIEW: Treatment options for late-stage biventricular heart failure
      are limited but include medical therapy with intravenous inotropes, biventricular
      assist devices (Bi-VADs) and the total artificial heart (TAH). In this
      manuscript, we review the indications, surgical techniques and outcomes for the
      TAH. RECENT FINDINGS: The TAH offers biventricular replacement, rather than
      'assistance', as the device is placed orthotopically after excision of the entire
      ventricular myocardium and all four native valves. In contrast to patients with
      Bi-VADs, patients with the TAH have no postoperative inotrope requirements,
      arrhythmias or inflow/outflow cannulae-related complications. Additionally,
      patients participate in rehabilitation early after device placement and the
      development of a portable drive may facilitate hospital discharge in the USA.
      Furthermore, total heart replacement may be ideal for heart failure associated
      with unique anatomical and mechanical complications. SUMMARY: The TAH is an
      effective therapeutic option for the treatment of patients dying of heart failure
      who may not be suitable candidates for left ventricular assist devices.

PMID- 22382502
TI  - Cardiac connexins, mutations and arrhythmias.
AB  - PURPOSE OF REVIEW: Connexins are the pore forming subunits of gap junction
      channels. They are essential for cardiac action potential propagation. Connexins
      are modified at the transcriptional or posttranslational levels under
      pathological states such as cardiac hypertrophy or ischemia, thus contributing to
      the arrhythmogenic substrate. However, the relation between nucleotide
      substitutions in the connexin gene and the occurrence of cardiac arrhythmias
      remains largely unexplored. RECENT FINDINGS: Recent studies have reported an
      association between nucleotide substitutions in the connexin40 (Cx40) and
      connexin43 (Cx43) genes (GJA5 and GJA1, respectively) and cardiac arrhythmias. Of
      note, however, germline mutations in Cx43 are considered causative of
      oculodentodigital dysplasia, a pleiotropic syndrome wherein cardiac
      manifestations are notoriously absent. SUMMARY: Here, we review some of the
      current knowledge on the association between cardiac connexins and inherited
      arrhythmias.

PMID- 22382503
TI  - EXTEND III: efficacy and safety of ranibizumab in South Korean and Taiwanese
      patients with subfoveal CNV secondary to AMD.
AB  - BACKGROUND: The purpose of this study was to investigate the efficacy and safety
      of intravitreal ranibizumab 0.5 mg in South Korean and Taiwanese patients with
      subfoveal choroidal neovascularization (CNV) secondary to age-related macular
      degeneration (AMD). METHODS: This was a 12-month, open-label, single-arm, multi
      center, phase III study. Ninety-five patients (Taiwanese: 51; South Korean: 44)
      were included in the study. Key outcome measures assessed included: mean change
      in best-corrected visual acuity (BCVA) from baseline to months 4 (primary
      endpoint) and 12 (secondary endpoint); other secondary endpoints comprising
      categorized mean change in BCVA from baseline at month 4 and month 12, mean
      change in BCVA from baseline at month 4 and month 12 per baseline
      characteristics; and incidence of ocular and non-ocular adverse events and
      serious adverse events (SAEs) at month 12. RESULTS: The mean BCVA change improved
      significantly (p < 0.0001) from baseline to both month 4 (+9.3 letters) and month
      12 (+10.1 letters). At month 12, the proportion of patients who gained >=5, 10,
      or 15 letters from baseline was 75.8%, 54.7%, and 32.6% respectively. Total and
      CNV lesion area significantly decreased from baseline (p < 0.0001). About 57% of
      patients showed complete absence of fluorescein leakage at month 12. Mean change
      from baseline visual acuity scores also increased significantly over time for all
      subgroups. At month 12, ocular SAEs occurred in 2.1% of patients (out of which
      one patient [1.1%] experienced endophthalmitis) and 16.8% of patients experienced
      non-ocular SAEs. There were no deaths reported during the study. CONCLUSIONS:
      Consistent with previous studies in Caucasian and Japanese populations, EXTEND
      III confirms that monthly intravitreal injections of ranibizumab 0.5 mg
      administered over 12 months is effective and well-tolerated in South Korean and
      Taiwanese patients with subfoveal CNV secondary to AMD.

PMID- 22382501
TI  - Genetic determinants of response to cardiovascular drugs.
AB  - PURPOSE OF REVIEW: To survey genetic variation contributing to variable
      responsiveness and toxicity to important cardiovascular drugs and highlight
      recent developments in the field of cardiovascular pharmacogenomics and
      personalized medicine. RECENT FINDINGS: Previously recognized pharmacogenomic
      associations with drug efficacy have been further validated (e.g. with
      clopidogrel and warfarin) and shown to influence clinically important outcomes.
      The clinical significance of variants modulating toxicity (e.g. SLCO1B1 with
      simvastatin) has also been confirmed. The genetic contribution to variable
      efficacy and toxicity of other important classes of cardiovascular drugs, such as
      beta-blockers, is becoming increasingly recognized. Prospective trials testing
      whether the use of genomic information improves clinical care are underway.
      Guidance based on the most well-established pharmacogenomic findings has appeared
      in prescribing labeling and is in the early stages of being implemented into
      routine clinical care. SUMMARY: Clinically validated gene variants that modulate
      responsiveness to cardiovascular drugs continue to be discovered and validated.
      Early steps are underway to translate these discoveries into clinical care.

PMID- 22382504
TI  - ABO-incompatible kidney transplantation enabled by non-antigen-specific
      immunoadsorption.
AB  - BACKGROUND: ABO-incompatible kidney transplantation performed after
      desensitization with antigen-specific immunoadsorption (IA) results in good
      outcomes. However, a unique single-use IA device is required, which creates high
      costs. METHODS: From August 2005 to August 2010, 19 patients were desensitized
      for ABO-incompatible living donor kidney transplantation. Six patients treated
      with a single-use antigen-specific IA device and 12 patients treated with a
      reusable non-antigen-specific IA device were analyzed. RESULTS: Six patients who
      received antigen-specific IA had a median of 5 IA treatments and 12 patients with
      non-antigen-specific IA had a median of 6 IA treatments preoperatively. Median
      average titer drop in Coombs technique was 1.2 in antigen-specific IA and 1.7 in
      non-antigen-specific IA. In two patients with antigen-specific IA and four
      patients with non-antigen-specific IA, additional plasmapheresis treatments were
      necessary for recipient desensitization. Despite six treatments with antigen
      specific IA and 12 plasmapheresis treatments, one patient with a starting
      isoagglutinin titer of 1:1024 (Coombs) could not be transplanted. The 18-month
      graft survival rate for the 17 ABO-incompatible living donor kidney transplants
      was 100%. One male recipient who was desensitized with antigen-specific IA died
      44 months after transplantation from sudden cardiac death with a serum creatinine
      of 1.2 mg/dL. At last follow-up, a median of 13 months after transplantation,
      median serum creatinine for 16 patients was 1.5 mg/dL, median glomerular
      filtration rate as estimated by the modification of diet in renal disease formula
      54 mL/min/1.73 m, and median urinary protein-to-creatinine ratio 0.1, with no
      differences between treatments. CONCLUSIONS: A reusable non-antigen-specific IA
      device allows high number of treatments at reasonable cost, and at the same time
      might deplete human leukocyte antigen-alloantibodies.

PMID- 22382505
TI  - A facile route for preparing a mesoporous palladium coordination polymer as a
      recyclable heterogeneous catalyst.
AB  - To overcome the separation difficulty of the palladium-based homogeneous
      catalyst, the palladium complex can be anchored on various supports such as
      silica, polymers and nanoparticles. For the same purpose, we describe a general
      and facile method to immobilize palladium bis(phosphine) complexes on the basis
      of the technique widely used for metal-organic framework (MOF) synthesis,
      yielding a mesoporous coordination polymer palladium-CP1. Although palladium
      complexes are generally not stable enough to allow further manipulation, we
      succeeded in preparation of a palladium coordination polymer without by-product
      Pd clusters or nanoparticles. The fresh palladium-CP1 catalyst exhibits a yield
      close to 55% for tolane at room temperature and 24 h in Sonogashira coupling of
      iodobenzene and phenylacetylene, as compared with a yield of 89% for its
      homogeneous counterpart [Pd(PPh(3))(2)Cl(2)]. Furthermore, this catalyst is
      stable enough to be reused more than four times with no Pd and Zn leaching.
      Therefore this new immobilization method offers great promise for the produce of
      recyclable palladium heterogeneous catalysts with higher activity and higher
      thermal and chemical stability in the future.

PMID- 22382506
TI  - Primary adenocarcinoma of the epididymis: the therapeutic role of retroperitoneal
      lymphadenectomy.
AB  - AIMS: This case report describes a rare case of adenocarcinoma of the epididymis
      and the role of locoregional surgery in the therapeutic algorithm. CLINICAL CASE:
      We report a case of primary adenocarcinoma of the epididymis in a 61-year-old man
      who was primarily examined for nodular enlargement of the head of the epididymis.
      Retroperitoneal lymphadenectomy which the patient underwent after radical
      orchiectomy revealed lymph node metastases, subsequently he received adjuvant
      chemotherapy. The patient remains free of disease for 20 months after surgery.
      CONCLUSIONS: Primary adenocarcinoma of epididymis is a rare finding with an
      unfavorable prognosis in higher stages as it responds poorly to radiotherapy and
      chemotherapy. Our case report confirms the importance of retroperitoneal
      lymphadenectomy in patients with local or locoregional disease. It may be
      curative even in case of proven lymphadenopathy and should be performed in all
      patients without distant metastases.

PMID- 22382507
TI  - Experimentally measured permanent dipoles induced by hydrogen bonding. The Stark
      spectrum of indole-NH3.
AB  - Hydrogen bond pairs involving the chromophore indole have been extensively
      studied in the gas phase. Here, we report high resolution electronic spectroscopy
      experiments on the indole-NH(3) hydrogen bond pair in the absence and presence of
      an electric field. The S(1)-S(0) origin band of this complex recorded in zero
      field at high resolution reveals two overlapping spectra; a consequence of NH(3)
      hindered internal rotation. The barrier to internal rotation is predicted by
      theory to be less than 20 cm(-1) in the ground state, therefore requiring a non
      rigid rotor Hamiltonian to interpret the spectra. Conducting the experiment in
      the presence of an applied electric field further perturbs the already congested
      spectrum of the complex, but makes possible the measurement of the permanent
      electric dipole moments in its S(0) and S(1) states. These values reveal
      significant changes in electron distribution that arise from hydrogen bonding
      effects.

PMID- 22382508
TI  - The phenology of Rubus fruticosus in Ireland: herbarium specimens provide
      evidence for the response of phenophases to temperature, with implications for
      climate warming.
AB  - To date, phenological research has provided evidence that climate warming is
      impacting both animals and plants, evidenced by the altered timing of
      phenophases. Much of the evidence supporting these findings has been provided by
      analysis of historic records and present-day fieldwork; herbaria have been
      identified recently as an alternative source of phenological data. Here, we used
      Rubus specimens to evaluate herbaria as potential sources of phenological data
      for use in climate change research and to develop the methodology for using
      herbaria specimens in phenological studies. Data relevant to phenology
      (collection date) were recorded from the information cards of over 600 herbarium
      specimens at Ireland's National Herbarium in Dublin. Each specimen was assigned a
      score (0-5) corresponding to its phenophase. Temperature data for the study
      period (1852 - 2007) were obtained from the University of East Anglia's Climate
      Research Unit (CRU); relationships between temperature and the dates of first
      flower, full flower, first fruit and full fruit were assessed using weighted
      linear regression. Of the five species of Rubus examined in this study, specimens
      of only one (R. fruticosus) were sufficiently abundant to yield statistically
      significant relationships with temperature. The results revealed a trend towards
      earlier dates of first flower, full flower and first fruit phenophases with
      increasing temperature. Through its multi-phenophase approach, this research
      serves to extend the most recent work-which validated the use of herbaria through
      use of a single phenophase-to confirm herbarium-based research as a robust
      methodology for use in future phenological studies.

PMID- 22382509
TI  - Validity of 6(th) edition of UICC TNM classification system for medullary thyroid
      carcinoma: a proposal for intraoperative evaluation of T category.
AB  - Medullary thyroid carcinoma (MTC) accounts for 1.4% of all thyroid malignancies
      in Japan. Here, we studied the validity of a staging system evaluated
      preoperatively (Stage), intraoperatively (intra-Stage), and pathologically
      (pStage) based on the 6(th) and 7(th) UICC TNM classifications. One hundred and
      nineteen MTC patients who did not show distant metastasis at diagnosis and
      underwent locally curative surgery were enrolled in this study (average follow-up
      period: 173.4 months). Twenty-year clinical (not biochemical) disease-free
      survival (DFS) rates of Stage I, II, III, and IVA patients based on the 6(th)
      edition were 100, 88.2, 66.8, and 38.9%, respectively. DFS of Stage IVA patients
      was significantly poorer than that of Stage III patients (p = 0.03137). However,
      using the 7(th) edition, only 1 patient was classified with Stage III. Intra
      Stage III patients based on the 6th edition showed a significantly poorer DFS (20
      year DFS 50.0%) than intra-Stage II patients (92.9%) (p = 0.02668), and DFS of
      intra-Stage IVA patients (38.9%) tended to be poorer than that of intra-Stage III
      patients (p = 0.05439). Only one patient was classified with intra-Stage III
      using the 7(th) edition. In pStage, as many as 56 patients (47.1%) were
      classified with pStage IVA employing both editions. Taken together, Stage and
      intra-Stage were more useful to accurately discriminate high-risk patients than
      pStage, and their 6(th) editions were better than 7(th) editions. Although the
      number of patients was small, our data showed the possibility that intra-Stage in
      the 6(th) edition was the best staging system for MTC patients.

PMID- 22382510
TI  - Caudal dysplasia, femoral hypoplasia-unusual facies syndrome and absent radius: a
      new association in infant of diabetic mother?
AB  - The Caudal dysplasia syndrome (CDS) and the femoral hypoplasia-unusual facies
      syndrome (FHUFS) have been reported to be more frequent among infants of diabetic
      mothers (IDMs). Infact, uncontrolled maternal diabetes is the most common cause
      of both the syndromes. Till now, there is no case report to suggest absent radius
      as a manifestation of IDMs. The authors report a rare case of newborn, who
      presented with features compatible with both CDS and FHUFS with an additional
      feature of absent radius, which is not reported in the literature so far. The
      possibility that all these features represent different manifestations of the
      same disorder is discussed here.

PMID- 22382511
TI  - Care of the HIV-exposed child--to breast feed or not?
AB  - Breast milk is the best form of nutrition for infants. However, it places infants
      born to HIV infected women at risk of acquiring HIV infection. Total avoidance of
      breastfeeding is the only way of completely avoiding HIV transmission through
      breast milk. However, this strategy has not proved to be viable in resource
      constrained nations. A high infection related mortality and morbidity, and a high
      prevalence of malnutrition have been observed in HIV exposed infants on
      replacement feeding. Exclusive breastfeeding for the first six months followed by
      rapid weaning has also not proved to be a good strategy, with a surge in
      infection related morbidity and malnutrition reported after weaning. Current
      evidence indicates that continued use of ARV prophylaxis to mother/infant
      starting during pregnancy and continued to cover the entire duration of
      breastfeeding offers the infant best chance of HIV free survival, combining the
      benefits of breast milk with safety induced by ARV prophylaxis.

PMID- 22382513
TI  - Coarctation of aorta in a child with proteus syndrome.

PMID- 22382512
TI  - Primary malignant liver tumors in children.
AB  - Liver tumors constitute only 1-4% of all solid tumors in children. Two-thirds of
      these are malignant. The primary malignant tumors are hepatoblastoma (HB),
      hepatocellular carcinoma (HCC), rhabdomyosarcoma (RMS), angiosarcoma, rhabdoid
      tumor, undifferentiated sarcoma and other rarer tumors. Of these HB is the
      commonest. The diagnosis of HB is based on the radiology, elevated levels of
      alpha-fetoprotein (alphaFP) and the histology/cytology. Staging is essential for
      risk categorization, risk adapted treatment and prognostication. The commonest
      staging and risk categorization system used today is PRETEXT system that is being
      used by nearly all multicentre trials (American, European, German, Japanese) in
      some way. Treatment of HB is multimodal with surgery and chemotherapy being the
      main modalities. Survival is not possible without complete surgical resection.
      Majority of tumors are unresectable at presentation but can be made resectable
      with chemotherapy, giving a resection rate of more than 85%. Cisplatin is the
      main stay of chemotherapy and is a part of all multidrug protocols. The 3-y
      overall survival (OS) today stands at 62%-70% but only 25% patients with
      metastasis get cured. Panhepatic tumors and those with local factors causing
      unresectability are now dealt with liver transplantation which has also given a
      survival rate of nearly 85%. The overall management of HB and HCC has evolved
      over the past 3 decades giving good long term survival rates for HB, though
      patients with HCC still do poorly. Successive therapeutic trials have focused
      attention on increasing the efficiency and reducing the toxicity and long term
      side effects of the treatment. Among the other uncommon tumors the rhabdoid tumor
      and angiosarcoma are chemoresistant and have a poor outcome while the
      undifferentiated sarcoma and rhabdomyosarcoma are now showing better response to
      the currently used chemotherapy combinations.

PMID- 22382514
TI  - Reversible lung disease due to abundant use of talcum powder.

PMID- 22382515
TI  - Chronic inflammation is correlated with percentage of body fat independent of the
      burden of infection.
AB  - The aim of this population-based study was to investigate the association of the
      percentage of body fat (BF) and high-sensitivity C-reactive protein (hs-CRP) when
      the infectious burden was adjusted for. A total of 1,546 subjects were randomly
      selected. BF was determined using bioelectrical impedance analysis. Sera were
      analyzed for IgG antibodies to Chlamydia pneumoniae, herpes simplex virus type 1,
      Helicobacter pylori, and cytomegalovirus using ELISA. Measurement of C-reactive
      protein (CRP) by a high-sensitivity CRP assay was performed. A linear
      relationship between an increase in the number of pathogens and CRP
      concentrations was observed (p = 0.007). Age-adjusted serum hs-CRP levels were
      correlated with percentage of BF in men (r = 0.28, p < 0.0001) and women (r =
      0.37, p < 0.0001). In multiple regression analyses, hs-CRP showed significant
      correlations with percentage of BF after controlling for age, sex, cardiovascular
      risk factors, and the infectious burden was divided into two, three, and four
      pathogens [(beta = 0.24, p < 0.0001), (beta = 0.2 1, p < 0.0001), and (beta =
      0.23, p = <0.0001), respectively]. In conclusion, there was a strong association
      between hs-CRP and percentage of body fat independent of viral and bacterial
      pathogens that had been previously associated with coronary artery disease as
      well as carotid atherosclerosis.

PMID- 22382516
TI  - Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of
      IL1B, IL6, and IL8 by gingival epithelial cells.
AB  - Porphyromonas gingivalis alters cytokine expression in gingival epithelial cells,
      stimulating inflammatory responses that may lead to periodontal disease. This
      study explored the effect of Lactobacillus acidophilus on the specific
      expressions of the interleukins (ILs) IL1B, IL6, and IL8 induced by the pathogen.
      Human gingival epithelial cells were co-cultured with P. gingivalis, L.
      acidophilus, or L. acidophilus + P. gingivalis; the control group consisted of
      the cells alone. Protein and gene expression levels of the ILs were detected
      using ELISA and qRT-PCR, respectively. The supernatant from the P. gingivalis
      group held significantly higher protein and mRNA levels of IL1B, IL6, and IL8,
      compared to the control group. In the mixed bacterial group (L. acidophilus + P.
      gingivalis), the levels of all three ILs decreased with increasing concentrations
      of L. acidophilus and were significantly different from the P. gingivalis group.
      This suggests that in gingival cells, L. acidophilus offsets the P. gingivalis
      induced secretion of these ILs in a dose-dependent manner.

PMID- 22382517
TI  - Role of caffeic acid phenethyl ester on mitomycin C induced clastogenesis:
      analysis of chromosome aberrations, micronucleus, mitotic index and adenosine
      deaminase activity in vivo.
AB  - The aim of the present investigation is to determine whether the caffeic acid
      phenethyl ester (CAPE) in combination with mitomycine-C (MMC) can ameliorate MMC
      induced clastogenesis in the bone marrow cells of mice. The scoring of
      chromosomal aberrations, mitotic activity and micronuclei were undertaken in the
      current study as markers of clastogenicity. The action of CAPE in adenosine
      deaminase enzyme (ADA) activities of serum, thymus and spleen were also
      investigated. The animals were orally administered CAPE alone at the doses 5 or
      10 mg kg b.wt.(-1) for 5 days then sacrificed 24 hours after the CAPE
      administration. MMC was administered to mice either alone at a single dose (2 mg
      kg b.wt.(-1)) by intraperitoneal injection, before or after CAPE treatment. Pre
      or post - treatment with two doses of CAPE significantly decreased the number of
      chromosomal aberrations, micronuclei and adapted the mitotic activity reduction
      in the bone marrow cells of mice induced by MMC when compared with only MMC given
      group. In addition, combination treatment with MMC caused a significant decrease
      in the activities of ADA in serum, thymus and spleen. The results of this study
      showed that ADA activity probably related to high levels of reactive oxygen
      species. This study concluded that the protective effect of CAPE against MMC
      clastogenesis resides at least in part, in its antioxidant effects.

PMID- 22382518
TI  - Innate stimulation of B1a cells enhances the autoreactive IgM repertoire in the
      NOD mouse: implications for type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We sought to determine whether the presence of natural
      autoreactive antibodies of B1a cell origin would play a role in the initiation of
      type 1 diabetes. METHODS: We compared IgM repertoires and B1a cell compartments
      in NOD and C57BL/6 mice. Serum IgM autoreactivity profiles were determined by
      ELISA and the secretory properties and activation status of B1a cells were
      characterised by enzyme-linked immunosorbent spot (ELISPOT) assay and flow
      cytometry. B1a cell response to innate activation was analysed by gene expression
      assays, ELISA and [(3)H]thymidine incorporation. The effect of NOD IgM produced
      by B1a cells on NOD.severe combined immunodeficient (SCID) beta cells was
      examined in co-cultures: IgM binding was measured by flow cytometry and real-time
      PCR was used to study oxidative stress responses. RESULTS: NOD mice displayed
      increased levels of serum anti-insulin IgM that were independent of the H2 locus,
      that were maintained up to prediabetic stages and that correlated with the NOD
      B1a cell secretion profile. NOD B1a cells had a naturally increased pattern of
      activation, expressed higher levels of toll-like-receptors (Tlrs) and responded
      to TLR stimulation in vitro with higher proliferation and increased capacity to
      secrete anti-type-1-diabetes-related IgM, but produced lower amounts of IL10. IgM
      of NOD B1a cell origin was able to bind to pancreatic beta cells in vitro and
      induce expression of inducible nitric oxide synthase (Nos2).
      CONCLUSIONS/INTERPRETATION: NOD B1a cells had a lower innate activation threshold
      for secretion of autoreactive IgM capable of triggering oxidative stress
      responses on binding to pancreatic beta cells; this provides an early mechanism
      that contributes to diabetes in a mouse model of type 1 diabetes.

PMID- 22382519
TI  - Lactogens protect rodent and human beta cells against glucolipotoxicity-induced
      cell death through Janus kinase-2 (JAK2)/signal transducer and activator of
      transcription-5 (STAT5) signalling.
AB  - AIMS/HYPOTHESIS: A leading cause of type 2 diabetes is a reduction in functional
      beta cell mass partly due to increased beta cell death, triggered by stressors
      such as glucolipotoxicity (GLT). This study evaluates the hypothesis that
      lactogens can protect beta cells against GLT and examines the mechanism behind
      the pro-survival effect. METHODS: The effect of exogenous treatment or endogenous
      expression of lactogens on GLT-induced beta cell death was examined in INS-1
      cells, and in rodent and human islets. The mechanism behind the pro-survival
      effect of lactogens was determined using an inhibitor, siRNAs, a dominant
      negative (DN) mutant, and Cre-lox-mediated gene deletion analysis. RESULTS:
      Lactogens significantly protect INS-1 and primary rodent beta cells against GLT
      induced cell death. The pro-survival effect of lactogens in rodent beta cells is
      mediated through activation of the Janus kinase-2 (JAK2)/signal transducer and
      activator of transcription-5 (STAT5) signalling pathway. Lactogen-induced
      increase in the anti-apoptotic B cell lymphoma-extra large (BCLXL) protein is
      required to mediate its pro-survival effects in both INS-1 cells and primary
      rodent beta cells. Most importantly, lactogens significantly protect human beta
      cells against GLT-induced cell death, and their pro-survival effect is also
      mediated through the JAK2/STAT5 pathway. CONCLUSIONS/INTERPRETATION: These
      studies, together with previous work, clearly demonstrate the pro-survival nature
      of lactogens and identify the JAK2/STAT5 pathway as an important mediator of this
      effect in both rodent and human beta cells. Future studies will determine the
      effectiveness of this peptide in vivo in the pathophysiology of type 2 diabetes.

PMID- 22382521
TI  - To test, or not to test: time for a MODY calculator?
AB  - To test, or not to test, that is often the question in diabetes genetics. This is
      why the paper of Shields et al in the current issue of Diabetologia is so warmly
      welcomed. MODY is the most common form of monogenic diabetes. Nevertheless, the
      optimal way of identifying MODY families still poses a challenge both for
      researchers and clinicians. Hattersley's group in Exeter, UK, have developed an
      easy-to-use MODY prediction model that can help to identify cases appropriate for
      genetic testing. By answering eight simple questions on the internet (
      www.diabetesgenes.org/content/mody-probability-calculator ), the doctor receives
      a positive predictive value in return: the probability that the patient has MODY.
      Thus, the classical binary (yes/no) assessment provided by clinical diagnostic
      criteria has been substituted by a more rational, quantitative estimate. The
      model appears to discriminate well between MODY and type 1 and type 2 diabetes
      when diabetes is diagnosed before the age of 35 years. However, the performance
      of the MODY probability calculator should now be validated in other settings than
      where it was developed-and, as always, there is room for some improvements and
      modifications.

PMID- 22382520
TI  - Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in
      beta cell glucotoxicity.
AB  - AIMS/HYPOTHESIS: This study was aimed at the elucidation of the pathogenesis of
      glucotoxicity, i.e. the mechanism whereby hyperglycaemia damages pancreatic beta
      cells. The identification of pathways in the process may help identify targets
      for beta cell-protective therapy. Carbohydrate response element-binding protein
      (ChREBP), a transcription factor that regulates the expression of multiple
      hyperglycaemia-induced genes, is produced in abundance in pancreatic beta cells.
      We hypothesise that ChREBP plays a pivotal role in mediating beta cell
      glucotoxicity. METHODS: We assessed the role of ChREBP in glucotoxicity in 832/13
      beta cells, isolated mouse islets and human pancreas tissue sections using
      multiple complementary approaches under control and high-glucose-challenge
      conditions as well as in adeno-associated virus-induced beta cell-specific
      overexpression of Chrebp (also known as Mlxipl) in mice. RESULTS: Under both in
      vitro and in vivo conditions, ChREBP activates downstream target genes, including
      fatty acid synthase and thioredoxin-interacting protein, leading to lipid
      accumulation, increased oxidative stress, reduced insulin gene
      transcription/secretion and enhanced caspase activity and apoptosis, processes
      that collectively define glucotoxicity. Immunoreactive ChREBP is enriched in the
      nucleuses of beta cells in pancreatic tissue sections from diabetic individuals
      compared with non-diabetic individuals. Finally, we demonstrate that induced beta
      cell-specific Chrebp overexpression is sufficient to phenocopy the glucotoxicity
      manifestations of hyperglycaemia in mice in vivo. CONCLUSIONS/INTERPRETATION:
      These data indicate that ChREBP is a key transcription factor that mediates many
      of the hyperglycaemia-induced activations in a gene expression programme that
      underlies beta cell glucotoxicity at the molecular, cellular and whole animal
      levels.

PMID- 22382522
TI  - Berberine inhibits norepinephrine-induced apoptosis in neonatal rat
      cardiomyocytes via inhibiting ROS-TNF-alpha-caspase signaling pathway.
AB  - OBJECTIVE: To determine the effect of berberine (Ber) on norepinephrine (NE)
      induced apoptosis in neonatal rat cardiomyocytes. METHODS: The cultured neonatal
      rat cardiomyocytes were treated with NE in the presence or absence of Ber. The
      activity of lactate dehydrogenase (LDH) in the culture medium was examined, and
      apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)
      conjugated annexin-V, and propidine iodide (PI) staining. In addition, the
      activities of caspases-2 and-3 were measured by a fluorescent assay kit. The
      level of secreted tumor necrosis factor alpha (TNF-alpha) and production of
      intracellular reactive oxygen species (ROS) were also determined. RESULTS: NE at
      a concentration of 50 MU mol/L induced an obvious increase in the activity of LDH
      in the culture medium (P<0.05), which was inhibited by coincubation with 0.5,
      1.0, or 2.0 MU mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced
      apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 MU
      mol/L markedly decreased the ROS and TNF-alpha productions (P <0.05) and
      inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE
      (P<0.05)h. CONCLUSION: The present study suggested that Ber could reduce NE
      induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF
      alpha-caspase signaling pathway.

PMID- 22382523
TI  - Protective effect of Chinese herbs for supplementing qi, nourishing yin and
      activating blood circulation on heart function of patients with acute coronary
      syndrome after percutaneous coronary intervention.
AB  - OBJECTIVE: To investigate the effects of Chinese herbs for supplementing qi,
      nourishing yin and activating blood circulation on heart function of patients
      with acute coronary syndrome (ACS) after successful percutaneous coronary
      intervention (PCI). METHODS: One hundred patients with ACS after successful PCI
      were randomly assigned to a Western medicine (WM) treatment group (WMG) and a
      combined treatment group (CMG) treated by Chinese herbs for supplementing qi,
      nourishing yin and activating blood circulation, besides Western medicine
      treatment, with 50 cases in each group. Both treatment courses were 6 months. The
      followup was scheduled at baseline, 6 months and 1 year after PCI, and New York
      Heart Association (NYHA) functional class, Chinese medicine (CM) symptom scores,
      blood stasis syndrome scores, and major adverse cardiovascular events (MACE) were
      observed, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP)
      and hyper-sensitivity C-reactive protein (Hs-CRP) were measured, an
      echocardiogram was conducted to examine left ventricular ejection fraction
      (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end
      systolic volume (LVESV), inter-ventricular septal thickness (IVST), left
      ventricular posterior wall thickness (LVPWT), and ventricular wall motion index
      (VWMI). RESULTS: Compared with the baseline, LVEF significantly increased
      (P<0.01), and CM symptom scores, blood stasis syndrome scores, VWMI, LVEDV,
      LVESV, NT-proBNP, and Hs-CRP all decreased (P<0.01) in both groups at 6 months
      and at 1 year after PCI. There were no significant differences in all the above
      parameters at 1 year vs those at 6 months after PCI (P>0.05). VWMI, LVEDV, LVESV,
      NT-proBNP, Hs-CRP, LVEF, and CM symptom and blood stasis syndrome scores were all
      improved obviously in CMG than those in WMG (P<0.05 or P<0.01) at 6 months and at
      1 year after PCI. There were no significant differences in NYHA functional class
      between CMG and WMG at different follow-up timepoints; it was notable that value
      was 0.054 when comparing the cases of NYHA functional class between the two
      groups at 1-year follow-up. During the 1-year follow-up, 3 MACE and 11 MACE
      occurred in CMG and WMG, respectively; the MACE rate in CMG was lower than that
      in WMG (6% vs 22%, P<0.05). CONCLUSION: Chinese herbs for supplementing qi,
      nourishing yin and activating blood circulation could improve heart function,
      reduce the CM symptom scores and blood stasis syndrome scores, and decrease the
      incidence of MACE in patients with ACS after successful PCI.

PMID- 22382524
TI  - Development of an ease-of-use remote healthcare system architecture using RFID
      and networking technologies.
AB  - The study aims to provide an ease-of-use approach for senior patients to utilize
      remote healthcare systems. An ease-of-use remote healthcare system (RHS)
      architecture using RFID (Radio Frequency Identification) and networking
      technologies is developed. Specifically, the codes in RFID tags are used for
      authenticating the patients' ID to secure and ease the login process. The patient
      needs only to take one action, i.e. placing a RFID tag onto the reader, to
      automatically login and start the RHS and then acquire automatic medical
      services. An ease-of-use emergency monitoring and reporting mechanism is
      developed as well to monitor and protect the safety of the senior patients who
      have to be left alone at home. By just pressing a single button, the RHS can
      automatically report the patient's emergency information to the clinic side so
      that the responsible medical personnel can take proper urgent actions for the
      patient. Besides, Web services technology is used to build the Internet
      communication scheme of the RHS so that the interoperability and data
      transmission security between the home server and the clinical server can be
      enhanced. A prototype RHS is constructed to validate the effectiveness of our
      designs. Testing results show that the proposed RHS architecture possesses the
      characteristics of ease to use, simplicity to operate, promptness in login, and
      no need to preserve identity information. The proposed RHS architecture can
      effectively increase the willingness of senior patients who act slowly or are
      unfamiliar with computer operations to use the RHS. The research results can be
      used as an add-on for developing future remote healthcare systems.

PMID- 22382525
TI  - SnCl2/TiCl3-mediated deoximation of oximes in an aqueous solvent.
AB  - A simple procedure for SnCl(2)/TiCl(3)-mediated deoximation of ketoximes in an
      aqueous solvent is reported. Under the conditions developed in this effort,
      various ketones and aldehydes are produced in good to excellent yields.

PMID- 22382526
TI  - Fluorescence-based multiplex protein detection using optically encoded
      microbeads.
AB  - Potential utilization of proteins for early detection and diagnosis of various
      diseases has drawn considerable interest in the development of protein-based
      multiplex detection techniques. Among the various techniques for high-throughput
      protein screening, optically-encoded beads combined with fluorescence-based
      target monitoring have great advantages over the planar array-based multiplexing
      assays. This review discusses recent developments of analytical methods of
      screening protein molecules on microbead-based platforms. These include various
      strategies such as barcoded microbeads, molecular beacon-based techniques, and
      surface-enhanced Raman scattering-based techniques. Their applications for label
      free protein detection are also addressed. Especially, the optically-encoded
      beads such as multilayer fluorescence beads and SERS-encoded beads are successful
      for generating a large number of coding.

PMID- 22382527
TI  - Sulfur-functionalized N-heterocyclic carbene complexes of Pd(II): syntheses,
      structures and catalytic activities.
AB  - N-heterocyclic carbenes (NHCs) can be easily modified by introducing functional
      groups at the nitrogen atoms, which leads to versatile coordination chemistry as
      well as diverse catalytic applications of the resulting complexes. This article
      summarizes our contributions to the field of NHCs bearing different types of
      sulfur functions, i.e., thioether, sulfoxide, thiophene, and thiolato. The
      experimental evidence for the truly hemilabile coordination behavior of a Pd(II)
      thioether-NHC complex has been reported as well. In addition, complexes bearing
      rigid CSC-pincer ligands have been synthesized and the reasons for pincer versus
      pseudo-pincer formation investigated. Incorporation of the electron-rich thiolato
      function resulted in the isolation of structurally diverse complexes. The
      catalytic activities of selected complexes have been tested in Suzuki-Miyaura,
      Mizoroki-Heck and hydroamination reactions.

PMID- 22382528
TI  - Macro-microscopic study on the toepad of ostrich (Struthio camelus).
AB  - The ostrich foot has four toepads, two on the 3rd digit, one on the 4th digit and
      one at metatarso-phalangeal joint. Previous studies have not detailed the histo
      morphological structure of these toepads. In this study, we have described the
      macroscopic and microscopic structures of the toepad of ostrich (Struthio
      camelus). Numerous papillae with different direction, length and thickness have
      been observed grossly on the ventral surface of each toepad. Histological
      examinations have revealed that the epidermis of the ostrich toepad, similar to
      other digitigrades, consists of an outer stratum corneum and an inner stratum
      germinativum (which is subdivided into basal, intermediate and transitional
      layers). The stratum corneum has several layers of flattened horny cells. The
      nuclei of basal cells have several mitotic figures. The cytoplasm of the stratum
      germinativum cells has multiple lipid droplets and multigranular bodies (in
      transitional cells only). Scanning electron microscopic examination revealed
      presence of collagen fibers in mid and deep dermis of each toepad. These fibers
      run parallel and connect to each other by very thin fibrils which are branched,
      crossed with each other in an oblique direction. Such arrangement of these
      collagen fibers, thin fibrils and presence of digital cushion are likely to be
      responsible for the protection of the underlying soft tissues and absorption of
      concussion.

PMID- 22382529
TI  - Pb5.0(1)In8.4(1)Bi1.6(1)S20, a new quaternary lead indium bismuth sulfide.
AB  - The title phase, first detected in the early 1980s but hitherto unpublished, has
      been resynthesized and structurally characterized. Unambiguous determination of
      the chemical composition was not possible by structure analysis alone, but
      required additional analytical methods. The complex structure shows a close
      similarity to the structures of two related compounds, one known by the formula
      Pb(1.6)In(8)Bi(4)S(19) and the other being the ternary compound Pb(6)In(10)S(21).
      This is despite the fact that the three phases correspond to very different Pb:Bi
      ratios. A geometric mechanism is described by which the three structures can be
      transformed into each other, provided that the heavy atoms Pb and Bi are treated
      as equivalent.

PMID- 22382530
TI  - [Co(II)4Mo(V)12O28(OH)12(H2O)12].12H2O: facilitating single-crystal growth by
      deuteration.
AB  - The structure of the neutral heterometal oxide cluster dodecaaqua-di-MU(3)
      hydroxido-deca-MU(2)-hydroxido-octacosaoxidotetracobalt(II)dodecamolybdenum(V)
      dodecahydrate, [Mo(12)O(28)(MU(2)-OH)(10)(MU(3)-OH)(2){Co(H(2)O)(3)}(4)], is
      virtually identical to the previously reported Ni(II) analogue [Mo(12)O(28)(MU(2)
      OH)(10)(MU(3)-OH)(2){Ni(II)(H(2)O)(3)}(4)] [Muller, Beugholt, Kogerler, Bogge,
      Budko & Luban (2000). Inorg. Chem. 39, 5176-5177], the first molecular magnet to
      exhibit signs of magnetostriction. The formation kinetics of the neutral cluster
      species, which is insoluble in water, can be significantly slowed by the use of
      deuterated reactants in order to grow single crystals of sufficient size for
      single-crystal X-ray diffraction studies using standard diffractometers. One half
      of the main cluster and six solvent water molecules constitute the asymmetric
      unit. The main cluster is located on a mirror plane.

PMID- 22382531
TI  - Ammonium and caesium carbonate peroxosolvates: supramolecular networks formed by
      hydrogen bonds.
AB  - Diammonium carbonate hydrogen peroxide monosolvate, 2NH(4)(+).CO(3)(2-).H(2)O(2),
      (I), and dicaesium carbonate hydrogen peroxide trisolvate, 2Cs(+).CO(3)(2
      ).3H(2)O(2), (II), were crystallized from 98% hydrogen peroxide. In (I), the
      carbonate anions and peroxide solvent molecules are arranged on twofold axes. The
      peroxide molecules act as donors in only two hydrogen bonds with carbonate
      groups, forming chains along the a and c axes. In the structure of (II), there
      are three independent Cs(+) ions, two of them residing on twofold axes, as are
      two of the four peroxide molecules, one of which is disordered. Both structures
      comprise complicated three-dimensional hydrogen-bonded networks.

PMID- 22382532
TI  - Ni(5-delta)Sn4Zn (delta~0.25) from single-crystal data.
AB  - Work on the ternary Ni-Sn-Zn phase diagram revealed the existence of the title
      compound pentanickel tetratin zinc, Ni(3.17)Sn(2.67)Zn(0.67) [Schmetterer et al.
      (2012). Intermetallics, doi:10.1016/j.intermet.2011.05.025]. It crystallizes in
      the Ni(5)Ga(3)Ge(2) structure type (orthorhombic, Cmcm) and is related to the
      InNi(2) type (hexagonal, P6(3)/mmc) of the neighbouring Ni(3)Sn(2) high
      temperature (HT) phase, but is not a superstructure. The crystal structure was
      determined using single-crystal X-ray diffraction. Its homogeneity range was
      characterized using electron microprobe analysis. Phase analysis at various
      temperatures indicated that the phase decomposes between 1073 and 1173 K, where a
      more extended ternary solid solution of the Ni(3)Sn(2) HT phase was found
      instead.

PMID- 22382533
TI  - Poly[[diaquabis(MU2-crotonato-kappa3O:O,O')(crotonato-kappa2O,O')lanthanum(III)]
      adenine monosolvate monohydrate].
AB  - The asymmetric unit of the title compound,
      {[La(C(4)H(5)O(2))(3)(H(2)O)(2)].C(5)H(5)N(5).H(2)O}(n), consists of an La(III)
      cation, three crotonate (but-2-enoate) anions and two coordinated water molecules
      forming the neutral complex, completed by an external adenine molecule and one
      hydration water molecule. The LaO(10) coordination polyhedra, connected through
      the sharing of a single edge, form isolated chains running along the [100]
      direction. These one-dimensional structures are characterized by two different
      centrosymmetric La(2)O(2) loops, with La...La distances of 4.5394 (6) and 4.5036
      (6) A. The unbound adenine and water solvent molecules form a highly planar
      hydrogen-bonded array parallel to (110) (r.m.s. deviation from the mean plane <
      0.10 A) which intersects the isolated La-crotonate chains in a slanted fashion to
      form an extremely connected hydrogen-bonded three-dimensional structure.

PMID- 22382534
TI  - A novel three-dimensional CdII metal-organic framework based on [Cd6(malonate)6]
      metallomacrocycles with zeolite SOD (sodalite) topology: poly[ammine-MU3-malonato
      cadmium(II)].
AB  - A novel Cd(II) metal-organic framework, [Cd(C(3)H(2)O(4))(NH(3))](n), was
      synthesized by liquid diffusion conducted in the presence of ammonia. The Cd(II)
      atom has seven-coordinate O(6)N pentagonal-bipyramidal geometry. Six Cd(II)
      centers are joined by six malonate ligands to form an S(6)-symmetric
      [Cd(6)(malonate)(6)] metallomacrocycle, which is further extended through a side
      on chelating malonate ligand to form a three-dimensional network. Topologically,
      each Cd(II) center is connected to four others to yield an infinite three
      periodic four-coordinated SOD (sodalite) network with point symbol {4(2).6(4)}.
      The overall network structure in the crystal is maintained and stabilized by the
      presence of N-H...O hydrogen bonds.

PMID- 22382535
TI  - Bis(methanol-kappaO)dioxido[3,3'-(1H-1,2,4-triazole-3,5-diyl)diphenolato
      kappa3O,N4,O']uranium(VI) methanol monosolvate.
AB  - The structure of the title compound,
      [U(C(14)H(9)N(3)O(2))O(2)(CH(3)OH)(2)].CH(3)OH, is the first to be reported for
      an actinide complex including triazole ligands. The U(VI) atom exhibits a
      pentagonal-bipyramidal NO(6) coordination environment, involving two axial oxide
      ligands [U=O = 1.766 (3) and 1.789 (3) A], four equatorial O atoms [U-O = 2.269
      (3)-2.448 (3) A] from the ligand and the two coordinated methanol molecules, and
      one equatorial N atom [U-N = 2.513 (4) A] from the ligand. In the crystal
      structure, the complex molecules are linked via intermolecular N-H...O and O
      H...O hydrogen bonds to form a two-dimensional structure.

PMID- 22382536
TI  - (Pentane-2,4-dionato-kappa2O,O')(pyridin-2-amine-kappaN1)copper(II) and (pentane
      2,4-dionato-kappa2O,O')(pyrimidin-2-amine-kappaN1)copper(II).
AB  - The title compounds, [Cu(C(5)H(7)O(2))(2)(C(5)H(6)N(2))], (I), and
      [Cu(C(5)H(7)O(2))(2)(C(4)H(5)N(3))], (II), were prepared by the reaction of
      bis(pentane-2,4-dionato-kappa(2)O,O')copper(II) with pyridin-2-amine and
      pyrimidin-2-amine, respectively. From a chemical point of view, it is interesting
      that no Schiff base formation was observed. The compounds are isostructural, with
      both having a square-pyramidal coordination of the Cu(II) atom and intramolecular
      N-H...O hydrogen bonding. The additional N atom of the pyrimidin-2-amine ligand
      is not involved in hydrogen bonding or in metal coordination. In the crystal
      structure, chelate rings are involved in pi-pi interactions and molecules of (I)
      are linked together via N-H...O hydrogen bonds.

PMID- 22382537
TI  - Tricarbonyl(eta5-formylcyclopentadienyl)manganese(I) and tricarbonyl(eta5
      formylcyclopentadienyl)rhenium(I) containing short pi(CO)...pi(CO) and
      pi(CO)...pi interactions.
AB  - The structures of tricarbonyl(formylcyclopentadienyl)manganese(I),
      [Mn(C(6)H(5)O)(CO)(3)], (I), and tricarbonyl(formylcyclopentadienyl)rhenium(I),
      [Re(C(6)H(5)O)(CO)(3)], (II), were determined at 100 K. Compounds (I) and (II)
      both possess a carbonyl group in a trans position relative to the substituted C
      atom of the cyclopentadienyl ring, while the other two carbonyl groups are in
      almost eclipsed positions relative to their attached C atoms. Analysis of the
      intermolecular contacts reveals that the molecules in both compounds form stacks
      due to short attractive pi(CO)...pi(CO) and pi(CO)...pi interactions, along the
      crystallographic c axis for (I) and along the [201] direction for (II). Symmetry
      related stacks are bound to each other by weak intermolecular C-H...O hydrogen
      bonds, leading to the formation of the three-dimensional network.

PMID- 22382538
TI  - A novel dinuclear MoVI complex with tris(3,5-dimethyl-1H-pyrazol-1-yl)methane.
AB  - Recrystallization of [MoO(2)Cl{HC(3,5-Me(2)pz)(3)}]Cl [where HC(3,5-Me(2)pz)(3)
      is tris(3,5-dimethyl-1H-pyrazol-1-yl)methane] led to the isolation of large
      quantities of the dinuclear complex dichlorido-2kappa(2)Cl-MU-oxido-kappa(2)O:O
      tetraoxido-1kappa(2)O,2kappa(2)O-[tris(3,5-dimethyl-1H-pyrazol-1-yl
      1kappaN(2))methane]dimolybdenum(IV) acetonitrile monosolvate,
      [Mo(2)Cl(2)O(4)(C(16)H(22)N(6))].CH(3)CN or [{MoO(2)Cl(2)}(MU(2)-O){MoO(2)[HC(3,5
      Me(2)pz)(3)]}].CH(3)CN. At 150 K, this complex cocrystallizes in the orthorhombic
      space group Pbcm with an acetonitrile molecule. The complex has mirror symmetry:
      only half of the complex constitutes the asymmetric unit and all the heavy
      elements (namely Mo and Cl) are located on the mirror plane. The acetonitrile
      molecule also lies on a mirror plane. The two crystallographically independent
      Mo(6+) centres have drastically different coordination environments: while one Mo
      atom is hexacoordinated and chelated to HC(3,5-Me(2)pz)(3) (which occupies one
      face of the octahedron), the other Mo atom is instead pentacoordinated, having
      two chloride anions in the apical positions of the distorted trigonal bipyramid.
      This latter coordination mode of Mo(VI) was found to be unprecedented. Individual
      complexes and solvent molecules are close-packed in the solid state, mediated by
      various supramolecular contacts.

PMID- 22382539
TI  - A novel three-dimensional CdII coordination polymer: poly[[aquabis(2,2'
      bipyridine)(MU5-pyrazol-1-ide-3,5-dicarboxylato)(MU4-pyrazol-1-ide-3,5
      dicarboxylato)(MU3-pyrazole-3,5-dicarboxylato)tetracadmium(II)] dihydrate].
AB  - The title compound,
      {[Cd(4)(C(5)H(2)N(2)O(4))(C(5)HN(2)O(4))(2)(C(10)H(8)N(2))(2)(H(2)O)].2H(2)O}(n),
      crystallized in the monoclinic space group P2(1)/n and displays a three
      dimensional architecture. The asymmetric unit is composed of four
      crystallographically independent Cd(II) centres, two triply deprotonated pyrazole
      3,5-dicarboxylic acid molecules, one doubly deprotonated pyrazole-3,5
      dicarboxylic acid molecule, two 2,2'-bipyridine ligands, one coordinated water
      molecule and two interstitial water molecules. Interestingly, the Cd(II) centers
      exhibit two different coordination numbers. Two Cd(II) centres adopt a distorted
      octahedral arrangement and a third a trigonal-prismatic geometry, though they are
      all hexacoordinated. However, the fourth Cd(II) center is heptacoordinated and
      displays a pentagonal-bipyramidal geometry. The three anionic ligands adopt MU(3)
      , MU(4)- and MU(5)-bridging modes, first linking Cd(II) centers into a one
      dimensional wave-like band, then into a wave-like layer and finally into a three
      dimensional coordination framework, which is stabilized by hydrogen bonds.

PMID- 22382540
TI  - Two isomorphous lanthanide crotonate complexes: di-MU-but-2-enoato
      bis[diaquabis(but-2-enoato)dysprosium(III)] adenine monosolvate heptahydrate and
      the samarium(II) analogue.
AB  - The asymmetric unit of the title dimeric compounds,
      [Ln(2)(C(4)H(5)O(2))(6)(H(2)O)(4)].C(5)H(5)N(5).7H(2)O, with Ln = Dy, (I), and
      Sm, (II), consists of an Ln(III) cation, three crotonate (but-2-enoate) anions
      and two coordinated water molecules forming the neutral complex, cocrystallized
      with half of an external adenine molecule and 3.5 water molecules. The metal
      complex has crystallographic inversion symmetry. The LnO(9) coordination
      polyhedra are connected through the sharing of a single edge to form isolated
      dimeric units, with Ln...Ln separations of 4.1766 (12) A for (I) and 4.2340 (12)
      A for (II). The unbound adenine molecule and one of the solvent water molecules
      are disordered around an inversion centre into two overlapping, equally
      populated, units. The structure is sustained by a complex hydrogen-bonding scheme
      involving all possible O-H and N-H groups as donors, and crotonate and water O
      and adenine N atoms as acceptors. The system is compared with recently published
      related compounds.

PMID- 22382541
TI  - 5-[4-(diethoxyphosphoryl)-2,3,5,6-tetrafluorophenyl]-10,15,20
      tris(pentafluorophenyl)porphyrin.
AB  - The title compound, C(48)H(20)F(19)N(4)O(3)P, prepared by the nucleophilic attack
      of triethyl phosphite on one of the 4-fluoro atoms of 5,10,15,20
      tetrakis(pentafluorophenyl)porphyrin, contains a single molecule in the
      asymmetric unit. The porphyrin unit is almost planar [largest non-H atom
      deviation = 0.174 (6) A], and has the planes of the neighbouring benzene rings
      oriented at angles ranging from 64.3 (2) to 89.6 (3) degrees  relative to the
      porphyrin core. The P=O group is almost coplanar with the attached benzene ring,
      subtending an angle of 4.0 (3) degrees . Several weak supramolecular
      interactions, namely C-H...pi, C-F...pi, P=O...pi, C-H...(O,F) and F...F
      contacts, contribute to the crystal packing.

PMID- 22382542
TI  - Trimethylurea.
AB  - The title compound, C(4)H(10)N(2)O, crystallizes with two independent molecules
      in the space group Cmc2(1). The first molecule lies in a crystallographic mirror
      plane with x = 0, whereas the second molecule lies on a general position with x
      is approximately equal to 1/3. Each molecule forms classical N-H...O=C hydrogen
      bonds, thereby leading to chains of molecules parallel or antiparallel,
      respectively, to the polar c axis.

PMID- 22382543
TI  - Antidiarrhetic loperamide hydrochloride.
AB  - Single crystals of the anhydrous form of the title compound {systematic name: 1
      [3-(dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxy-4-(4-chlorophenyl)piperidin
      1-ium chloride}, C(29)H(34)ClN(2)O(2)(+).Cl(-), were obtained by diffusion of
      acetone into a solution in 2-propanol. In the structure, N-H...Cl(-) and O
      H...Cl(-) hydrogen bonds connect neighbouring molecules and chloride anions to
      form chains along the c-axis direction. Neighbouring chains along the b-axis
      direction are connected by intermolecular C-H...Cl(-) contacts, defining layers
      parallel to the (100) planes. The layers are connected by weak intermolecular C
      H...Cl interactions only, which may account for the plate-like shape of the
      crystals.

PMID- 22382544
TI  - C-H...X (X = O, N or pi) interactions in benzyl carbamate.
AB  - The crystal packing and interaction energy of benzyl carbamate, C(8)H(9)NO(2),
      have been analysed in detail by the PIXEL method. Benzyl carbamate forms layers
      of hydrogen-bonded molecules, with the layers connected by weaker C-H...pi
      interactions. According to the PIXEL analysis, combinations of C-H...X (X = O, N
      or pi) interactions are comparable in energy with hydrogen bonding. These
      interactions are necessary for explaining the geometry and the assembly of the
      layers.

PMID- 22382545
TI  - 2-[2-(pyrrolidin-2-yl)propan-2-yl]-1H-pyrrole and its amide derivative 1-{2-[2
      (1H-pyrrol-2-yl)propan-2-yl]pyrrolidin-1-yl}ethanone.
AB  - In the title compounds, C(11)H(18)N(2), (II), and C(13)H(20)N(2)O, (III), the
      pyrrolidine rings have twist conformations. Compound (II) crystallizes with two
      independent molecules (A and B) in the asymmetric unit. The mean planes of the
      pyrrole and pyrrolidine rings are inclined to one another by 89.99 (11) and 89.35
      (10) degrees  in molecules A and B, respectively. In (III), the amide derivative
      of (II), the same dihedral angle is much smaller, at only 13.42 (10) degrees . In
      the crystal structure of (II), the individual molecules are linked via N-H...N
      hydrogen bonds to form inversion dimers, each with an R(2)(2)(12) graph-set
      motif. In the crystal structure of (III), the molecules are linked via N-H...O
      hydrogen bonds to form inversion dimers with an R(2)(2)(16) graph-set motif.

PMID- 22382546
TI  - (2RS,4SR)-7-bromo-2-exo-(2-chlorophenyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2
      b]azepine: sheets built by the pi-stacking of hydrogen-bonded chains.
AB  - The molecules of the title compound, C(20)H(15)BrClNO, are linked into chains by
      a C-H...pi(arene) hydrogen bond, in which the acceptor is the brominated ring of
      the naphthalene unit, and these chains are linked by an aromatic pi-pi stacking
      interaction, again involving the naphthalene unit, into a sheet structure.

PMID- 22382547
TI  - Chain formation by disordered, but correlated, hydrogen bonds in cis-(2RS,4SR)-2
      (thiophen-2-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol and cis-(2RS,4SR)-2-(5
      methylthiophen-2-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol.
AB  - The closely related compounds cis-(2RS,4SR)-2-(thiophen-2-yl)-2,3,4,5-tetrahydro
      1H-1-benzazepin-4-ol, C(14)H(15)NOS, (I), and cis-(2RS,4SR)-2-(5-methylthiophen-2
      yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-4-ol, C(15)H(17)NOS, (II), both
      crystallize with Z' = 2 in the space group P-1. In (I), the thienyl substituent
      in one of the two independent molecules is disordered over two sets of atomic
      sites having occupancies of 0.856 (2) and 0.144 (2). In both compounds, the two
      independent hydroxy O atoms are both within 2.8 A of the hydroxy O atoms of two
      neighbouring molecules, and all of the hydroxy H atoms are disordered, each over
      two sites. The resulting O-H...O hydrogen bonds generate two similar but distinct
      C(4)(4)(8) chains, depending upon which hydroxy H-atom sites are occupied or
      vacant, with full correlation of the hydroxy H-atom occupancies within each
      chain. Comparisons are made with the supramolecular assembly in some related
      compounds.

PMID- 22382548
TI  - Nine closely related tetrahydro-1,4-epoxy-1-benzazepines carrying pendant
      heterocyclic substituents: hydrogen-bonded supramolecular assembly in zero, one
      and two dimensions.
AB  - The structures are reported of nine closely related tetrahydro-1,4-epoxy-1
      benzazepines carrying pendant heterocyclic substituents, namely: 2-exo-(5
      nitrofuran-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine,
      C(14)H(12)N(2)O(4), (I), 7-fluoro-2-exo-(1-methyl-1H-pyrrol-2-yl)-2,3,4,5
      tetrahydro-1,4-epoxy-1H-1-benzazepine, C(15)H(15)FN(2)O, (II), 7-fluoro-2-exo-(5
      methylfuran-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine,
      C(15)H(14)FNO(2), (III), 7-fluoro-2-exo-(3-methylthiophen-2-yl)-2,3,4,5
      tetrahydro-1,4-epoxy-1H-1-benzazepine, C(15)H(14)FNOS, (IV), 7-fluoro-2-exo-(5
      methylthiophen-2-yl)-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine,
      C(15)H(14)FNOS, (V), 7-chloro-2-exo-(5-methylfuran-2-yl)-2,3,4,5-tetrahydro-1,4
      epoxy-1H-1-benzazepine, C(15)H(14)ClNO(2), (VI), 2-exo-(5-methylfuran-2-yl)-7
      trifluoromethoxy-2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine,
      C(16)H(14)F(3)NO(3), (VII), 2-exo-(3-methylthiophen-2-yl)-7-trifluoromethoxy
      2,3,4,5-tetrahydro-1,4-epoxy-1H-1-benzazepine, C(16)H(14)F(3)NO(2)S, (VIII), and
      2-exo-(5-nitrofuran-2-yl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1,4-epoxy-1H-1
      benzazepine, C(15)H(11)F(3)N(2)O(5), (IX). All nine compounds crystallize in
      centrosymmetric space groups as racemic mixtures with configuration (2RS,4SR).
      There are no direction-specific interactions between the molecules in (V). The
      molecules in (III), (IV), (VI) and (VII) are linked into simple chains, by means
      of a single C-H...O hydrogen bond in each of (III), (VI) and (VII), and by means
      of a single C-H...pi(arene) hydrogen bond in (IV), while the molecules in (VIII)
      are linked into a chain of rings. In each of (I) and (II), a combination of one C
      H...O hydrogen bond and one C-H...pi(arene) hydrogen bond links the molecules
      into sheets, albeit of completely different construction in the two compounds. In
      (IX), the sheet structure is built from a combination of four independent C-H...O
      hydrogen bonds and one C-H...pi(arene) hydrogen bond. Comparisons are made with
      some related compounds.

PMID- 22382549
TI  - 1-[(1-ethoxypropylidene)amino]-2-ethyl-4-(4-hydroxybenzyl)imidazol-5(4H)-one.
AB  - The racemic title compound, C(17)H(23)N(3)O(3), isolated from the reaction of L-(
      )-tyrosine hydrazide with triethyl orthopropionate in the presence of a catalytic
      quantity of p-toluenesulfonic acid (p-TsOH), crystallizes with Z' = 1 in a
      centrosymmetric monoclinic unit cell. The molecule contains two planar fragments,
      viz. the benzene and imidazole rings, linked by two C-C single bonds. The
      dihedral angle between the two planes is 59.54 (5) degrees  and the molecule
      adopts a synclinal conformation. The HOMA (harmonic oscillator model of
      aromaticity) index, calculated for the benzene ring, demonstrates no substantial
      interaction between the two pi-electron delocalization regions in the molecule.
      In the crystal structure, there is an O-H...N hydrogen bond that links the
      molecules along the c axis.

PMID- 22382550
TI  - Nimustine hydrochloride: the first crystal structure determination of a 2
      chloroethyl-N-nitrosourea hydrochloride derivative by X-ray powder diffraction
      and solid-state NMR.
AB  - Nimustine hydrochloride [systematic name: 4-amino-5-({[N-(2-chloroethyl)-N
      nitrosocarbamoyl]amino}methyl)-2-methylpyrimidin-1-ium chloride],
      C(9)H(14)ClN(6)O(2)(+).Cl(-), is a prodrug of CENU (chloroethylnitrosourea) and
      is used as a cytostatic agent in cancer therapy. Its crystal structure was
      determined from laboratory X-ray powder diffraction data. The protonation at an N
      atom of the pyrimidine ring was established by solid-state NMR spectroscopy.

PMID- 22382551
TI  - Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic
      activity. IV. Diesters of benzoylcarbonohydrazonodithioic acid.
AB  - Dimethyl (3,4-dichlorobenzoyl)carbonohydrazonodithioate,
      C(10)H(10)Cl(2)N(2)OS(2), (D1), dibenzyl (3,4
      dichlorobenzoyl)carbonohydrazonodithioate, C(22)H(18)Cl(2)N(2)OS(2), (D2),
      dimethyl (3,4-dichlorobenzoyl)-1-methylcarbonohydrazonodithioate,
      C(11)H(12)Cl(2)N(2)OS(2), (D3), 3,4-dichloro-N'-(1,3-dithiolan-2-ylidene)-N
      methylbenzohydrazide, C(11)H(10)Cl(2)N(2)OS(2), (D4), were synthesized as
      potential tuberculostatics. Compound (D1) (with two molecules in the asymmetric
      unit) was the only one showing tuberculostatic activity of the same range as the
      common drugs isoniazid and pyrazinamide. The molecular structures of the studied
      compounds depend on the substitution at the N atom adjacent to the carbonyl
      group. In the case of the unsubstituted derivatives (D1) and (D2), their central
      frames are generally planar with a twist of the 3,4-dichlorophenyl ring by 30-40
      degrees . Until now, coplanarity of the aromatic ring with the
      (methylene)carbonohydrazone fragment has been considered a prerequisite for
      tuberculostatic activity. The N-methylated derivatives (D3) and (D4) show an
      additional twist along the N-C(=O) bond by 20-30 degrees  due to the spatial
      repulsion introduced by the methyl substituent.

PMID- 22382552
TI  - Indications, complications and long-term follow-up of patients undergoing
      percutaneous endoscopic gastrostomy: A retrospective study.
AB  - INTRODUCTION: Gastroenterology units have faced a major increase in referrals for
      PEG insertion over the last decade. For this reason we decided to review our PEG
      insertion procedures with regard to indications, complications and follow-up.
      MATERIALS AND METHODS: The indications, success of procedure, complications, long
      term results of PEG in patients of Gulhane Military Medical Academy, Haydarpasa
      Training Hospital between October 2002 and April 2009 were retrospectively
      evaluated. RESULTS: 81 patients had undergone PEG insertion and follow-up
      information has been available for 77 patients. 40 were men with the mean age of
      all patients 70.74 +/- 20.82 (range 20 to 104 years). PEG was successfully placed
      in all patients except in one patient who had gastric bleeding during the
      procedure. There was only one mortality related with the placement procedure. The
      most common indication for PEG was neurologic disorders in 71 (92%) patients.
      Other indications were head and neck cancers in 6 (8%) patients. Median follow-up
      period was 12 months (range, 3 days to 78 months). PEG related complications were
      seen in only 14 patients (18.2%) in 16 events with a total complication rate as
      21%. CONCLUSIONS: PEG placement is a safe procedure and well-tolerated with a low
      mortality and complication rate even in older patients who have multiple co
      morbidities under adequate precautions.

PMID- 22382553
TI  - [Primary immune thrombocytopenia in adults: diagnostics and treatment consensus
      statement of the Austrian Society of Hematology and Oncology (OGHO)].
AB  - Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease,
      but might be associated with severe or even life-threatening bleeding
      complications. The treatment of ITP has partly changed in recent years, due to
      new therapeutic options. International guidelines changed accordingly. This
      consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is
      not a new evaluation of the current evidence, but rather tries to discuss the
      available international guidelines and adapt them to the situation in Austria.
      The subject is primary ITP in adults only. Classification, epidemiology, clinical
      presentation and diagnostics of ITP, and especially the management of this
      disease, are discussed in detail. This includes current aspects of first, second,
      and third line therapies, splenectomy with its indications and contraindications,
      and the use of new therapeutic options like thrombopoetin receptor agonists
      (TRA).

PMID- 22382554
TI  - Population pharmacokinetic and pharmacodynamic modeling of MNRP1685A in
      cynomolgus monkeys using two-target quasi-steady-state (QSS) model.
AB  - MNRP1685A (anti-NRP1) is a fully human IgG1 monoclonal antibody against
      neuropilin-1 (NRP1), a protein necessary for blood vessel maturation. MNRP1685A
      binds to free membrane-bound NRP1 (mNRP1) and circulating NRP1 (cNRP1). Total
      cNRP1 increased in a dose-dependent manner following anti-NRP1 administration in
      mice, rats, and monkeys. The purpose of this study is to develop a mechanism
      based model to simultaneously describe the kinetics of both unbound drug
      (MNRP1685A) and total cNRP1 in cynomolgus monkeys. Pharmacokinetic (PK) and
      pharmacodynamic (PD) profiles after single- or multiple-dose administrations were
      well described by the two-target quasi-steady-state (QSS) model. The estimated
      nonspecific clearance was 3.26 mL/day/kg and central compartment volume was 38.2
      mL/kg. The maximum elimination rate for mNRP1-mediated disposition was 98.8
      nM/day. The synthesis rate (3.8 nM/day), degradation rate constant (1.53 day(
      1)), and complex elimination rate constant (0.260 day(-1)) for cNRP1 were also
      derived from the model. QSS constants were 6.94 nM for mNRP1 and 2.8 nM for
      cNRP1. The results suggest that cNRP1 has minimal effect on MNRP1685A PK while
      mNRP1 plays a major role in the target-mediated drug disposition. This finding is
      favorable as the desired pharmacological target is mNRP1, rather than cNRP1. The
      two-target QSS model provides mechanistic understanding of the nonlinear PK of
      MNRP1685A. Based on the model prediction, the free drug concentrations to
      maintain free mNRP1 and cNRP1 below 10% of baseline level are 10 and 20 MUg/mL,
      respectively. This serves as a target concentration for clinical dose selection,
      assuming cynomolgus monkeys are predictive for humans.

PMID- 22382555
TI  - Gender differences in psychosocial functioning of adolescents with symptoms of
      anxiety and depression: longitudinal findings from the Nord-Trondelag Health
      Study.
AB  - PURPOSE: To explore longitudinally gender differences in the associations between
      psychosocial functioning, subjective well-being and self-esteem among adolescents
      with and without symptoms of anxiety and depression. METHODS: Data were obtained
      from a major population-based Norwegian study, the Nord-Trondelag Health Study,
      in which 1,092 boys and 1,262 girls (86% of all invited) completed an extensive
      self-report questionnaire at baseline (mean age 14.4 years) and at follow-up
      (mean age 18.4 years). RESULTS: Gender was a moderator variable in the
      associations between symptoms of anxiety and depression and impairment, meaning
      that boys' functioning was impaired to a larger extent than girls' functioning. A
      statistically significant interaction effect between gender and symptoms of
      anxiety and depression was found at follow-up in terms of subjective well-being
      (p < 0.05), self-esteem (p < 0.05), academic problems (p < 0.01), behaviour
      problems (p < 0.01) and frequency of meeting friends (p < 0.001). Onset of
      symptoms between baseline and follow-up was associated with less frequent
      meetings with friends among boys, but not among girls. After remission of
      symptoms, boys still had more behaviour and academic problems, less frequently
      met friends and reported lower subjective well-being and self-esteem than boys
      who had no symptoms at both time points. No similar differences were found among
      the girls. CONCLUSION: Previous and ongoing symptoms of anxiety and depression
      had more negative consequences for boys than for girls. These findings may
      contribute to improved assessment and intervention methods tailored differently
      for each gender.

PMID- 22382556
TI  - Carbonate interlayered hydrotalcites-enhanced peroxynitrous acid
      chemiluminescence for high selectivity sensing of ascorbic acid.
AB  - In this study, Mg-Al-carbonate layered double hydroxides (denoted as Mg-Al-CO(3)
      LDHs) were found to catalyze the chemiluminescence (CL) emission from
      peroxynitrous acid (ONOOH). The enhanced CL signals resulted from the
      concentration of peroxynitrite (ONOO(-)) onto the LDHs surface by electrostatic
      attraction, meaning that ONOO(-) can interact with the intercalated carbonate
      easily and effectively. Moreover, ascorbic acid can react with ONOO(-), or its
      decomposition products (e.g., OH and NO(2)), resulting in a decrease in the CL
      intensity from the Mg-Al-CO(3) LDHs-catalyzed ONOOH reaction. Based on these
      findings, a sensitive, selective and rapid CL method was developed for the
      determination of ascorbic acid using Mg-Al-CO(3) LDHs-catalyzed ONOOH as a novel
      CL system. The CL intensity was proportional to the concentration of ascorbic
      acid in the range from 5.0 to 5000 nM. The detection limit (S/N = 3) was 0.5 nM
      and the relative standard deviation (RSD) for nine repeated measurements of 0.1
      MUM ascorbic acid was 2.6%. This method has been successfully applied to
      determine ascorbic acid in commercial liquid fruit juices with recoveries of 97
      107%. This work is not only of importance for a better understanding of the
      unique properties of LDHs-catalyzed CL but also of great potential for extensive
      applications in many fields, such as luminescence devices, bioanalysis, and
      labeling probes.

PMID- 22382557
TI  - Silent thyroiditis in uncommon setting.

PMID- 22382558
TI  - Transbronchial biopsy using endobronchial ultrasonography with a guide sheath
      increased the diagnostic yield of peripheral pulmonary lesions.
AB  - OBJECTIVE: The advantage of transbronchial biopsy (TBB) using endobronchial
      ultrasonography (EBUS) with a guide sheath (GS) over TBB without EBUS guidance
      was investigated in this study. MATERIALS AND METHODS: A retrospective chart
      review was conducted at Nagasaki University Hospital, Japan. Data were collected
      from all cases of peripheral pulmonary lesions (PPLs) undergoing either EBUS-GS
      guided TBB or TBB without EBUS guidance in our department from December 2003
      through November 2009. The diagnostic yield in each group was compared, after
      adjustment for other factors. RESULTS: In total 110 PPLs were investigated in 102
      patients: 65 (59.1%) were examined with EBUS-GS-guided TBB (EBUS-GS group) and 45
      (40.9%) were TBB without EBUS guidance (non-EBUS group). Both procedures were
      performed under x-ray fluoroscopy. Basic characteristics were similar between the
      two groups. Of all EBUS examined lesions, 53 (81.5%) were visualized by EBUS. The
      diagnostic yields in EBUS-GS group and non-EBUS group were 64.6% and 46.7%,
      respectively (p=0.08). Adjusting for size and location of lesions, the yield of
      EBUS-GS guidance was 1.46 (95% confidence interval 1.03 to 2.05) times higher
      than without EBUS guidance. When the lesion was visualized by EBUS, the
      diagnostic yield ratio was further increased to 1.63 (95% CI 1.16 to 2.27).
      CONCLUSION: EBUS-GS-guided TBB demonstrates a higher diagnostic yield than TBB
      without EBUS guidance.

PMID- 22382559
TI  - Peripartum cardiomyopathy presenting with syncope due to Torsades de pointes: a
      case of long QT syndrome with a novel KCNH2 mutation.
AB  - Peripartum cardiomyopathy (PPCM) is a cardiomyopathy of unknown cause that occurs
      in the peripartum period. We report a case of PPCM presenting with syncope 1
      month after an uncomplicated delivery. Electrocardiography showed Torsades de
      pointes (TdP) and QT interval prolongation. Echocardiography showed left
      ventricular systolic dysfunction and endomyocardial biopsy showed myocyte
      degeneration and fibrosis. Administration of magnesium sulfate and temporary
      pacing eliminated recurrent TdP. Genetic analyses revealed that recurrent TdP
      occurred via electrolyte disturbance and cardiac failure due to PPCM on the basis
      of a novel mutation in KCNH2, a gene responsible for inherited type 2 long QT
      syndrome.

PMID- 22382560
TI  - Two siblings diagnosed to have transthyretin-related familial amyloid
      cardiomyopathy around the same time at different hospitals.
AB  - Mutation in the transthyretin (TTR) gene may clinically manifest as
      cardiomyopathy. Here, we describe 69-year-old and 72-year-old brothers who were
      diagnosed as having TTR-related familial amyloid cardiomyopathy by endomyocardial
      biopsy at different hospitals at around the same time. They were not from an
      endemic area of familial amyloid polyneuropathy. Genetic analysis showed a base
      change in the TTR gene leading to a p.Val30Met mutation in both patients.
      Screening of family members, as well as detailed family history taking, is
      important for the diagnosis of cardiomyopathy of unknown etiology.

PMID- 22382561
TI  - Pleural empyema secondary to rupture of amoebic liver abscess.
AB  - Amoebiasis is a worldwide parasitic infection although it is more prevalent in
      the subtropical and tropical countries. Extraintestinal amoebic infections
      currently have been reported in increased numbers of male homosexuals and
      immunocompromised patients. Here, we present an interesting case of a 27-year-old
      homosexual man with pleural empyema secondary to rupture of amoebic liver
      abscess. Using chest tube and percutaneous liver abscess drainage, the patient
      was treated with metronidazole followed by iodoquinol. His general condition
      improved dramatically. After one-year of follow-up, there was no evidence of
      relapse on plain chest radiography and abdominal CT scan.

PMID- 22382562
TI  - A case of painless thyroiditis in a very early stage of pregnancy.
AB  - We report a case of painless thyroiditis detected during the first trimester of
      pregnancy. A 29-year-old Japanese woman was hospitalized because of
      thyrotoxicosis and she was confirmed to be pregnant. The gestational age was 4
      weeks. Blood examinations revealed negative TSH receptor antibodies, however, we
      started potassium iodide because we were unable to rule out Graves' disease.
      Thyroid hormone levels were normalized in 3 weeks and remained low even after
      discontinuation of medication. She received replacement therapy with
      levothyroxine sodium hydrate till 3 months after delivery. Painless thyroiditis
      can be one of the differential diagnoses of thyrotoxicosis in a very early stage
      of pregnancy.

PMID- 22382563
TI  - A case of myelolipoma with bilateral adrenal hyperaldosteronism cured after
      unilateral adrenalectomy.
AB  - Myelolipomas are adrenal tumors composed of both adipose and hematopoietic
      tissues which are rarely associated with primary aldosteronism (PA). Here, we
      report a case of myelolipoma associated with PA. Aldosterone hypersecretion from
      bilateral adrenal glands had been confirmed by adrenal venous sampling and
      pathological analyses, but PA was clinically cured after surgical removal of the
      unilateral adrenal gland together with the myelolipoma that was not producing
      aldosterone. It is suggested that myelolipomas may release some factors which
      stimulate aldosterone production in adrenal glands, although further
      investigation is necessary. Obesity-related hyperaldosteronism might in part
      participate in generation of hypertension in the present case.

PMID- 22382564
TI  - Haff disease after eating crayfish in east China.
AB  - Haff disease, first identified in Europe, is unexplained rhabdomyolysis in a
      person who ingested fish within the 24 hours before onset of illness. Cases of
      Haff disease after the consumption of fresh water fish have never been reported
      in China but have been frequently reported from the Baltic region. We first
      describe five cases of muscle weakness and rhabdomyolysis that occurred after
      eating crayfish in China and discuss the different epidemiologic and etiologic
      aspects of this disease.

PMID- 22382565
TI  - Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma in Sjogren's syndrome
      showing only the LIP pattern radiologically.
AB  - A 49-year-old woman with a 20-year history of Sjogren's syndrome (SS) was
      incidentally found to have an abnormal chest X-ray along with dyspnea and
      desaturation. Chest CT findings showed multiple cystic shadows, ground glass
      opacity, and small nodule-like lymphocytic interstitial pneumonia (LIP), which
      have been previously reported. She was diagnosed by surgical lung biopsy to have
      mucosa-associated lymphoid tissue (MALT) lymphoma. It was difficult to detect the
      presence of lymphoma by the use of only CT findings. Pulmonary involvement of SS
      occurs in various forms so that SS patients with pulmonary involvement should
      undergo open biopsy to reach a definitive diagnosis.

PMID- 22382566
TI  - Spontaneous regression of pulmonary involvement after smoking reduction and
      removal of and radiation therapy for Langerhans cell histiocytosis of the
      sphenoid bone: which comes first, the chicken or the egg?
AB  - Isolated pulmonary Langerhans cell histiocytosis (LCH) in adults is known to
      regress spontaneously after smoking cessation alone, but little is known about
      whether this rationale could also apply in cases of multisystem pulmonary LCH. In
      particular, pediatric patients with multisystem LCH including involvement in
      "risk organs" such as lungs often benefit from systemic chemotherapy. Here, we
      present a 37-year-old man with spontaneous regression of pulmonary lesions in
      multisystem LCH, achieved solely by smoking reduction following local treatment
      of bone lesions.

PMID- 22382567
TI  - A Japanese adult case of megalencephalic leukoencephalopathy with subcortical
      cysts with a good long-term prognosis.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently
      recognized neurological disease, and mutations in the MLC1 gene have been
      identified as the cause of the disorder. A 54-year-old Japanese woman with
      macrocephaly presented with progressive mental decline, gait disturbance due to
      spasticity and ataxia, and choreoathetotic movement in the left upper extremity.
      Brain magnetic resonance imaging (MRI) revealed characteristic subcortical cysts
      in addition to diffuse white matter involvement. Genetic analysis of the MLC1
      gene identified an S93L mutation in a homozygous state. This case is particularly
      valuable because of the lack of knowledge on the long-term prognosis of MLC.

PMID- 22382568
TI  - Immunohistochemical findings of an autopsied lung specimen from a patient with
      pandemic influenza (A/H1N1pdm) virus infection.
AB  - A 24-year-old female presented with fever and dry cough. Influenza A virus
      infection was suspected and the patient was treated with neuraminidase
      inhibitors. Five days after diagnosis, the patient developed persistent fever and
      dyspnea, and was diagnosed with severe pneumonia. Despite intensive treatment,
      the pneumonia worsened and the patient died 14 days after admission. At autopsy,
      a diffuse alveolar damage (DAD) pattern was observed. Immunohistochemical
      evaluation indicated severe epithelial damage, resulting in successive
      regeneration of alveolar type II cells followed by marked proliferation of smooth
      muscle cells and an increase of collagen fibers at the tip of alveolar orifices.

PMID- 22382569
TI  - Stewart-Treves syndrome after cervical cancer.

PMID- 22382570
TI  - Multiple intracranial aneurysms associated with hyper-IgE syndrome.

PMID- 22382571
TI  - Mycetoma foot caused by Aspergillus in a diabetic patient.

PMID- 22382572
TI  - Reconstruction of the (001) surface of TiO2 nanosheets induced by the fluorine
      surfactant removal process under UV-irradiation for dye-sensitized solar cells.
AB  - The champion dye-sensitized solar cells (DSSCs) based on TiO(2) nanoparticles
      nearly reach the limit of photo-current density using the black dye or zinc
      porphyrin dye as sensitizer. However, the way to make ordinary DSSCs more
      efficient as well as to understand the mechanism is still essential. Here we
      present an elegant UV irradiation treatment of TiO(2) nanosheets to enhance the
      performance of DSSCs based on the TiO(2) nanosheets via room temperature removal
      of inorganic surfactants and reconstruction of the (001) surface of TiO(2)
      nanosheets, killing two birds with one stone. UV irradiation was utilized to
      remove the fluorine-surfactant on the surface of anatase TiO(2) nanosheets with a
      high percentage of exposed {001} facets which were synthesized with the aid of
      hydrofluoric acid. The nanosheets treated with UV irradiation for 40 min had the
      advantage of improving the photoelectric conversion efficiency of DSSCs by 17.6%,
      compared to that without UV treatment when they were introduced into DSSCs as
      photoanode materials. The improved efficiency was ascribed to more dye
      adsorption. A theoretical calculation proposed that UV irradiation induced
      microfaceted steps on the TiO(2) surface by two domain (1 * 4) reconstruction
      after UV irradiating the (1 * 1) (001) surface. The microfaceted steps increase
      the active surface area of the TiO(2) nanosheets by increasing the exposure of
      titanium atoms and engendering active sites.

PMID- 22382573
TI  - (1)H, (15)N, and (13)C chemical shift assignments of the calflagin Tb24 flagellar
      calcium binding protein of Trypanosoma brucei.
AB  - Flagellar calcium binding proteins are expressed in a variety of trypanosomes and
      are potential drug targets for Chagas disease and African sleeping sickness. We
      report complete NMR chemical shift assignments of the flagellar calcium binding
      protein calflagin Tb24 of Trypanosoma brucei. (BMRB no. 18011).

PMID- 22382574
TI  - Density functional calculations for a high energy density compound of formula C6H
      6-n (NO 2) n.
AB  - A series of polynitroprismanes, C(6)H(6-n )(NO(2))(n) (n = 1-6) intended for use
      as high energy density compounds (HEDCs) were designed computationally. Their
      electronic structures, heats of formation, interactions between nitro groups,
      specific enthalpies of combustion, bond dissociation energies, and explosive
      performances (detonation velocities and detonation pressures) were calculated
      using density functional theory (DFT) with the 6-311 G** basis set. The results
      showed that all of the polynitroprismanes had high positive heats of formation
      that increased with the number of substitutions for the prismane derivatives,
      while the specific enthalpy of combustion decreased as the number of nitro groups
      increased. In addition, the range of enthalpy of combustion reducing is getting
      smaller. Interactions between ortho (vicinal) groups deviate from the group
      additivity rule and decrease as the number of nitro groups increases. In terms of
      thermodynamic stability, all of the polynitroprismanes had higher bond
      dissociation energies (BDEs) than RDX and HMX. Detonation velocities and
      detonation pressures were estimated using modified Kamlet-Jacobs equations based
      on the heat of detonation (Q) and the theoretical density of the molecule (rho).
      It was found that rho, D, and P are strongly linearly related to the number of
      nitro groups. Taking both their energetic properties and thermal stabilities into
      account, pentanitroprismane and hexanitroprismane are potential candidate HEDCs.

PMID- 22382576
TI  - Opening the paddlewheel: unusual coordination of [Mo2] dumbbells in the chain
      structures of A[Mo2(CF3SO3)5].2CF3SO3H (A = Na, Rb, Cs).
AB  - The reaction of Mo(II)acetate, concentrated triflic acid and the alkaline metal
      triflates A(CF(3)SO(3)) (A = Na, Rb, Cs) in sealed glass ampoules at 110  degrees
      C yielded red single crystals of A[Mo(2)(CF(3)SO(3))(5)].2CF(3)SO(3)H (A = Na:
      triclinic, P-1, Z = 4, a = 13.714(1) A, b = 14.339(1) A, c = 21.340(2) A, alpha =
      81.78(1) degrees , beta = 75.21(1) degrees , gamma = 62.65(1) degrees ; A =
      Rb/Cs: monoclinic, P2(1)/m, Z = 2, a = 11.561(1)/11.584(1) A, b =
      14.817(1)/14.9472(8) A, c = 11.6208(1)/11.744(1) A, beta = 112.38(1)/113.48(1)
      degrees ). The crystal structures contain dumbbell shaped [Mo(2)] moieties
      surrounded by three chelating and four monodentate triflate anions leading to an
      opening of the typical paddlewheel fragment at one of its edges. The monodentate
      triflate anions are connected to further [Mo(2)] dumbbells leading to infinite
      anionic chains according to
      (infinity)(1)[Mo(2)(CF(3)SO(3))(3/1)(CF(3)SO(3))(4/2)](-). The charge balance is
      achieved by the alkaline metal ions that are additionally coordinated by triflic
      acid molecules. Theoretical investigations were preformed on the open paddlewheel
      fragment and are in good agreement with the experimental findings. According to
      DTA/TG measurements and the XRD investigations the decomposition of the compounds
      occurs in multiple steps and leads to MoO(2) and A(2)MoO(4).

PMID- 22382575
TI  - Molecular docking studies of protein-nucleotide complexes using MOLSDOCK
      (mutually orthogonal Latin squares DOCK).
AB  - Understanding the principles of protein receptor recognition, interaction, and
      association with molecular substrates and inhibitors is of principal importance
      in the drug discovery process. MOLSDOCK is a molecular docking method that we
      have recently developed. It uses mutually orthogonal Latin square sampling
      (together with a variant of the mean field technique) to identify the optimal
      docking conformation and pose of a small molecule ligand in the appropriate
      receptor site. Here we report the application of this method to simultaneously
      identify both the low energy conformation and the one with the best pose in the
      case of 62 protein-bound nucleotide ligands. The experimental structures of all
      these complexes are known. We have compared our results with those obtained from
      two other well-known molecular docking software, viz. AutoDock 4.2.3 and GOLD
      5.1. The results show that the MOLSDOCK method was able to sample a wide range of
      binding modes for these ligands and also scores them well.

PMID- 22382578
TI  - Electronic clinical decision support systems attitudes and barriers to use in the
      oncology setting.
AB  - BACKGROUND: There is little evidence regarding attitudes to clinical decision
      support systems (CDSS) in oncology. AIMS: We examined the current usage,
      awareness, and concerns of Irish medical oncologists and oncology pharmacists in
      this area. METHODS: A questionnaire was sent to 27 medical oncologists and 34
      oncology pharmacists, identified through professional interest groups.
      Respondents ranked concerns regarding their use of a CDSS on a scale from 1 to 4,
      with 4 being most important. RESULTS: Overall, 67% (41/61) responded, 48% (13/27)
      of oncologists and 82% (28/34) of pharmacists surveyed. Concerns included
      "difficulty defining complex clinical situations with a set of rules" (mean +/-
      SD) (3.2 +/- 0.9), "ensuring evidence base is up to date and relevant" (3.2 +/-
      0.9) and "lack of clinically relevant suggestions" (2.9 +/- 0.9). Ninety-three
      percent reported using a CDSS but 54% were unaware of this. CONCLUSION: While
      there are benefits to using a CDSS, concerns must be addressed through user
      education. This may be a starting point for a user-centred design approach to the
      development of future local systems through a consultative process.

PMID- 22382579
TI  - Edarbyclor: an ARB/chlorthalidone combination for hypertension.

PMID- 22382580
TI  - Clobazam (Onfi) for Lennox-Gastaut syndrome.

PMID- 22382581
TI  - Glucarpidase (Voraxaze) for methotrexate toxicity.

PMID- 22382582
TI  - In brief: immediate-release oxycodone (Oxecta) for pain.

PMID- 22382583
TI  - Effects of retinal eccentricity and acuity on global-motion processing.
AB  - The present study assessed direction discrimination with moving random-dot
      cinematograms at retinal eccentricities of 0, 8, 22, and 40 deg. In addition,
      Landolt-C acuity was assessed at these eccentricities to determine whether
      changes in motion discrimination performance covaried with acuity in the retinal
      periphery. The results of the experiment indicated that discrimination thresholds
      increased with retinal eccentricity and directional variance (noise), independent
      of acuity. Psychophysical modeling indicated that the results for eccentricity
      and noise could be explained by an increase in channel bandwidth and an increase
      in internal multiplicative noise.

PMID- 22382584
TI  - Matrix composition regulates three-dimensional network formation by endothelial
      cells and mesenchymal stem cells in collagen/fibrin materials.
AB  - Co-cultures of endothelial cells (EC) and mesenchymal stem cells (MSC) in three
      dimensional (3D) protein hydrogels can be used to recapitulate aspects of
      vasculogenesis in vitro. MSC provide paracrine signals that stimulate EC to form
      vessel-like structures, which mature as the MSC transition to the role of mural
      cells. In this study, vessel-like network formation was studied using 3D
      collagen/fibrin (COL/FIB) matrices seeded with embedded EC and MSC and cultured
      for 7 days. The EC:MSC ratio was varied from 5:1, 3:2, 1:1, 2:3 and 1:5. The
      matrix composition was varied at COL/FIB compositions of 100/0 (pure COL), 60/40,
      50/50, 40/60 and 0/100 (pure FIB). Vasculogenesis was markedly decreased in the
      highest EC:MSC ratio, relative to the other cell ratios. Network formation
      increased with increasing fibrin content in composite materials, although the
      40/60 COL/FIB and pure fibrin materials exhibited the same degree of
      vasculogenesis. EC and MSC were co-localized in vessel-like structures after 7
      days and total cell number increased by approximately 70%. Mechanical property
      measurements showed an inverse correlation between matrix stiffness and network
      formation. The effect of matrix stiffness was further investigated using gels
      made with varying total protein content and by crosslinking the matrix using the
      dialdehyde glyoxal. This systematic series of studies demonstrates that matrix
      composition regulates vasculogenesis in 3D protein hydrogels, and further
      suggests that this effect may be caused by matrix mechanical properties. These
      findings have relevance to the study of neovessel formation and the development
      of strategies to promote vascularization in transplanted tissues.

PMID- 22382585
TI  - Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and
      cyclophosphamide plus celecoxib in patients with advanced refractory
      gastrointestinal cancers.
AB  - AIMS: To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy
      plus celecoxib (CXB) for the treatment of patients with heavily pre-treated
      advanced gastrointestinal malignancies. METHODS: Thirty-eight patients received
      500 mg/mq(2) CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100
      mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH(2),
      GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth
      factor (VEGF), soluble VE-cadherin (sVE-C) and thrombospondin-1 (TSP-1) levels
      were detected by ELISA and real-time PCR of CD133 gene expression on peripheral
      blood mononuclear cell was also performed. RESULTS: Seventeen patients (45%)
      obtained stable disease (SD) with a median duration of 5.8 ms (range, 4.2-7.4).
      Median progression free survival (PFS) and overall survival (OS) were 2.7 ms (95%
      CI, 1.6-3.9 ms) and 7.1 ms (95% CI, 4.3-9.9 ms), respectively. No toxicities of
      grade >1 were observed. Pharmacokinetics of 27 patients (13/14, SD/progressive
      disease, PD) after the first treatment of UFT revealed that 5-FU AUC and C(max)
      values greater than 1.313 h * MUg/ml and 0.501 MUg/ml, respectively, were
      statistically correlated with stabilization of disease and prolonged PFS/OS. VEGF
      and sVE-C plasma levels were greater in the PD group when compared to SD group.
      CD133 expression increased only in the PD patients. CONCLUSION: Metronomic UFT
      and CTX with CXB in heavily pre-treated gastrointestinal patients were well
      tolerated and associated with interesting activity. Potential predictive
      pharmacokinetic parameters and pharmacodynamic biomarkers have been found.

PMID- 22382586
TI  - Non-canonical Cajal bodies form in the nucleus of late stage avian oocytes
      lacking functional nucleolus.
AB  - In the somatic cell nucleus, there are several universal domains such as
      nucleolus, SC35-domains, Cajal bodies (CBs) and histone locus bodies (HLBs).
      Among them, CBs were described more than 100 years ago; however, we still do not
      have a final understanding of their nature and biological significance. The giant
      nucleus of avian and amphibian growing oocytes represents an advantageous model
      for analysis of functions and biogenesis of various nuclear domains.
      Nevertheless, in large-sized avian oocytes that contain transcriptionally active
      lampbrush chromosomes, CB-like organelles have not been identified yet. Here we
      demonstrate that in the pigeon (Columba livia) oocyte nucleus, characterized by
      absence of any functional nucleoli, extrachromosomal spherical bodies contain TMG
      capped spliceosomal snRNAs, core proteins of Sm snRNPs and the protein coilin
      typical for CBs, but not splicing factor SC35 nor the histone pre-mRNA 3'-end
      processing factor symplekin. The results establish that coilin-rich nuclear
      organelles in pigeon late-stage oocyte are not the equivalents of HLBs but belong
      to a group of CBs. At the same time, they do not contain the snoRNP/scaRNP
      protein fibrillarin involved in 2'-O-methylation of snoRNAs and snRNAs. Thus, the
      nucleus of late-stage pigeon oocytes houses CB-like organelles that have an
      unusual molecular composition and are implicated in the snRNP biogenesis pathway.
      These data demonstrate that snRNP-rich non-canonical CBs can form in the absence
      of nucleolus. We argue that pigeon oocytes represent a new promising model to
      investigate CB modular organization, functions and formation mechanism.

PMID- 22382587
TI  - Morphology and chemical characteristics of subepithelial laminar nerve endings in
      the rat epiglottic mucosa.
AB  - The laminar nerve endings are distributed in the laryngeal mucosa, and described
      as sensory receptors evoked by laryngeal pressure changes. The present study
      aimed to determine detailed morphological characteristics of the laryngeal
      laminar endings of the rat. Immunohistochemistry for Na(+)-K(+)-ATPase, alpha(3)
      subunit, showed that laminar endings were distributed in the entire laryngeal
      surface of the epiglottis. The parent axons of the endings were thick in
      diameter, and they were branched and continued to the endings. In some cases,
      several endings from different parent axons fused into a large complex structure
      of 500 MUm in width. The laminar endings were also immunoreactive for vesicular
      glutamate transporter 1 (vGLUT1) and vGLUT2, but not for P2X(3) purinoceptor.
      Around the laminar endings, terminal Schwann cells with immunoreactivity for S
      100 protein were closely associated with axon terminals. Use of scanning electron
      microscopy with alkaline maceration method showed that the terminal Schwann cells
      consisted of a rounded perinuclear region and lamellar cytoplasmic processes.
      Ultrastructurally, axon terminals with numerous mitochondria were partly covered
      with Schwann cell sheath, and some terminals intruded into the epithelial layer.
      Clear vesicles of 50 nm in diameter were also observed especially in small
      cytoplasmic processes of 400 nm to 1 MUm in size. The results in the present
      study suggested that the laminar endings in epiglottic mucosa have morphological
      characteristics of slowly adapting mechanoreceptors and contribute to sensation
      of laryngeal pressure via mucosal tension.

PMID- 22382588
TI  - Ixabepilone-associated peripheral neuropathy: data from across the phase II and
      III clinical trials.
AB  - PURPOSE: Dose-limiting neuropathy is a major adverse event associated with most
      of the microtubule-stabilizing agent-based chemotherapy regimens. Ixabepilone, a
      semisynthetic analogue of the natural epothilone B, has activity against a wide
      range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone
      treatment, is usually mild to moderate, predominantly sensory and cumulative.
      Preclinical studies demonstrate that ixabepilone and taxanes produce a similar
      neurotoxicity profile. METHODS: We searched databases of phase II/III clinical
      trials involving patients receiving ixabepilone as a monotherapy or in
      combination with capecitabine for incidences of neuropathy. Potential risk
      factors for grade 3/4 PN were identified by a Cox regression analysis on a
      dataset of 1,540 patients with different tumor types across multiple studies.
      RESULTS: Rates for incidence of ixabepilone-induced severe PN (Common Terminology
      Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast
      cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was
      rare (<= 1%). Common symptoms included numbness, paresthesias, and sometimes
      dysesthesias. Cox regression analysis identified only preexisting neuropathy as a
      risk factor for increased ixabepilone-associated PN. The management of PN has
      been primarily through dose adjustments (dose delays and/or dose reduction).
      Patients had resolution of their neuropathy within a median time of 5 to 6 weeks.
      CONCLUSIONS: PN is a dose-limiting toxicity associated with ixabepilone
      treatment, is reversible in most patients, and can be managed with dose reduction
      and delays.

PMID- 22382589
TI  - Testicular cancer survivors' supportive care needs and use of online support: a
      cross-sectional survey.
AB  - INTRODUCTION: The supportive care needs of testicular cancer survivors have not
      been comprehensively studied. Likewise, there is limited research on their use of
      the Internet or social media applications--tools that are popular among young
      adults and which could be used to address their needs. METHODS: Two hundred and
      four testicular cancer patients receiving care at an urban cancer center
      completed a questionnaire assessing supportive care needs and the use and
      preferences for online support. We examined the associations between patient
      characteristics and met or unmet supportive care needs and the use of testicular
      cancer online communities. RESULTS: Respondents had more met (median 8.0,
      interquartile range (IQR) 10.0) than unmet (median 2.0, IQR 7.0) needs. The
      majority (62.5%) reported at least one unmet need, most commonly (25%) concerning
      financial support, body image, stress, being a cancer survivor, and fear of
      recurrence. Patients who were younger, had nonseminoma testicular cancer, or
      received treatment beyond surgery had more needs, and those who were unemployed
      had more unmet needs. The majority of respondents (71.5%) were social media users
      (e.g., Facebook), and 26% had used a testicular cancer online support community.
      Reasons for nonuse were lack of awareness (34.3%), interest (30.9%), trust
      (4.9%), and comfort using computers (2.5%). Users were more likely to speak
      English as a first language and have more needs. CONCLUSIONS: At least one in
      four testicular cancer survivors has unmet needs related to financial support,
      body image, stress, being a cancer survivor, and fear of recurrence. A web-based
      resource may be a useful strategy to consider given the high prevalence of social
      media use in this sample and their desire for online support. Efforts are needed
      to raise awareness about online peer support resources and to overcome barriers
      to their use.

PMID- 22382590
TI  - Clearing obstructed totally implantable central venous access ports: an efficient
      protocol using a second needle.
AB  - Totally implantable central venous access ports (IVAPs) are frequently used in
      oncology to assure chemotherapy delivery and other tasks. Obstruction of IVAPs is
      rare, but when it does occur it may result in treatment delays and/or invasive
      surgery for the patient. An IVAP unblocking protocol was implemented by the
      nursing staff of our department. The protocol is based on a precise decision tree
      comprising several progressive steps: (1) needle exchange; (2) if no result is
      observed, placement of a second needle and reservoir flushing with normal saline;
      and (3) if no result is observed, use of urokinase in the two-needle system.
      During 1 year, all consecutive patients presenting an obstructed IVAP in our unit
      benefited from this protocol. Medical files were then retrospectively reviewed to
      look for complication and for factors associated with blocked IVAPs. A total of
      12 patients were included. The rate of successful IVAP unblocking was 92% (n =
      11/12). The only unblocking failure was due to a mechanical obstruction, i.e., a
      bent catheter. No local or general complications were reported immediately after
      the unblocking protocol or in the following month. In 83% of the cases,
      obstruction occurred during use of IVAPs. Mains treatments administered when
      obstruction occurred were mannitol 20% (25%) and perfusion completed but non
      flushed (50%). In the remaining 17%, obstruction was present before any action
      (at needle insertion). With all due caution because of the retrospective nature
      of this study, the IVAP unblocking protocol presented here appears to be
      efficacious and safe, and thus can be recommend for clinical practice.

PMID- 22382591
TI  - Genome sequence comparison of two United States live attenuated vaccines of
      infectious laryngotracheitis virus (ILTV).
AB  - This study was conducted to identify unique nucleotide differences in two U.S.
      chicken embryo origin (CEO) vaccines [LT Blen (GenBank accession: JQ083493)
      designated as vaccine 1; Laryngo-Vac((r)) (GenBank accession: JQ083494)
      designated as vaccine 2] of infectious laryngotracheitis virus (ILTV) genomes
      compared to an Australian Serva vaccine reference ILTV genome sequence [Gallid
      herpesvirus 1 (GaHV-1); GenBank accession number: HQ630064]. Genomes of the two
      vaccine ILTV strains were sequenced using Illumina Genome Analyzer 2X of 36
      cycles of single-end reads. Results revealed that few nucleotide differences (23
      in vaccine 1; 31 in vaccine 2) were found and indicate that the US CEO strains
      are practically identical to the Australian Serva CEO strain, which is a European
      origin vaccine. The sequence differences demonstrated the spectrum of variability
      among vaccine strains. Only eight amino acid differences were found in ILTV
      proteins including UL54, UL27, UL28, UL20, UL1, ICP4, and US8 in vaccine 1.
      Similarly, in vaccine 2, eight amino acid differences were found in UL54, UL27,
      UL28, UL36, UL1, ICP4, US10, and US8. Further comparison of US CEO vaccines to
      several ILTV genome sequences revealed that US CEO vaccines are genetically close
      to both the Serva vaccine and 63140/C/08/BR (GenBank accession: HM188407) and are
      distinct from the two Australian-origin CEO vaccines, SA2 (GenBank accession:
      JN596962) and A20 (GenBank accession: JN596963), which showed close similarity to
      each other. These data demonstrate the potential of high-throughput sequencing
      technology to yield insight into the sequence variation of different ILTV
      strains. This information can be used to discriminate between vaccine ILTV
      strains and further, to identify newly emerging mutant strains of field isolates.

PMID- 22382592
TI  - Associations between diurnal changes in Goldmann tonometry, corneal geometry, and
      ocular response analyzer parameters.
AB  - PURPOSE: To investigate the possible covariations between diurnal changes in
      Goldmann applanation tonometry (GAT) estimates of intraocular pressure (IOP),
      central corneal thickness (CCT), central corneal radius, and ocular response
      analyzer measures of corneal hysteresis and corneal resistance factor (CRF).
      METHODS: Twenty-five healthy normal subjects (age, 21 +/- 2 years) had central
      corneal radius, ocular response analyzer, GAT, and CCT measurements performed in
      1 eye at multiple times for more than 24 hours. Measurements were taken at 17:00
      and repeated every 2 hours until 23:00. Subjects then slept uninterrupted
      overnight for approximately 8 hours. On awakening, readings were taken at a 20
      minute frequency from 7:00 to 9:00 inclusive, followed by 2 hourly intervals
      until 17:00. RESULTS: The maximum variation in GAT for more than 24 hours was 2.5
      mm Hg, and these fluctuations were predicted by the diurnal variations of CCT
      (0.37 mm Hg DeltaGAT/10 MUm CCT, P < 0.01) and CRF (0.68 mm Hg DeltaGAT/mm Hg
      CRF, P < 0.01). The diurnal changes in corneal hysteresis and CRF both covaried
      with those of CCT (0.16 and 0.30 mm Hg/10 MUm DeltaCCT, respectively, both Ps <
      0.01). None of these associations was statistically different during and after
      the nominal period of resolution from overnight corneal swelling (2-way
      interactions, all Ps > 0.05). CONCLUSIONS: If the IOP is assumed to be
      independent of corneal parameters, the clinically significant 24-hour variation
      in GAT being partially predicted by the changes in CCT and CRF suggests that the
      diurnal variation in corneal parameters affects tonometry measurements. CRF may
      also be dependent on the level of IOP.

PMID- 22382593
TI  - Interface fluid syndrome in routine cataract surgery 10 years after laser in situ
      keratomileusis.
AB  - PURPOSE: Interface fluid syndrome is an unusual complication after laser in situ
      keratomileusis (LASIK). We present a case of interface fluid syndrome after
      cataract surgery in a patient who had previous LASIK surgery. METHODS: A 62-year
      old man underwent routine cataract surgery on the left eye 10 years after LASIK
      on both eyes. The day after surgery, the intraocular pressure (IOP) was 21 mm Hg
      and a pocket of fluid was present in the interface LASIK wound. The patient was
      treated with 0.50% timolol eye drops twice daily. RESULTS: The problem resolved
      within 1.5 months. Two months later, the patient underwent routine cataract
      surgery of the right eye. The next day, the IOP was 11 mm Hg and LASIK interface
      fluid was present. The patient was treated with 0.5% timolol eye drops twice
      daily. Two months after the surgery, the problem had completely resolved.
      CONCLUSIONS: Ocular hypertension and traumatic endothelial cell damage could have
      been the causes of the syndrome. Although the IOP was not very high, previous
      LASIK could have led us to underestimate the IOP.

PMID- 22382594
TI  - Comparative analysis of the basement membrane composition of the human limbus
      epithelium and amniotic membrane epithelium.
AB  - PURPOSE: Human amniotic membrane has been widely used as substrate for ex vivo
      expansion and transplantation of limbal epithelial cells. To further clarify its
      suitability as a surrogate niche for limbal stem cells and progenitor cells, we
      analyzed the composition of the amniotic epithelial basement membrane, with
      special focus on the expression of limbus-specific matrix components. METHODS:
      Cryosections of corneoscleral specimens obtained from 10 human donor eyes and of
      6 amniotic membrane specimens obtained at cesarean section were stained by
      indirect immunofluorescence using a broad panel of antibodies against basement
      membrane components. RESULTS: Both amniotic and limbal epithelial basement
      membranes showed positive immunoreactivity for collagen type IV alpha1, alpha2,
      alpha5, and alpha6 chains; collagens type VII, XV, XVI, XVII, and XVIII; laminin
      alpha3, beta1, beta2, beta3, gamma1, and gamma2 chains; laminin-111 and laminin
      332; nidogen-1 and nidogen-2; fibronectin; fibulin-2; fibrillin-2; perlecan; and
      agrin. Both types of basement membrane were negative for collagen type IV alpha3
      and alpha4 chains, collagen type V, and laminin alpha4 chain. Limbal basement
      membrane components, which were not detected in amniotic membrane, included
      laminin alpha1, alpha2, alpha5, and gamma3 chains; BM40/SPARC; tenascin-C;
      matrilin-2; endostatin; and collagen type XVIII. CONCLUSIONS: Despite extensive
      similarities in basement membrane composition between amniotic and corneolimbal
      epithelia, the lack of limbus-specific environmental factors argues against the
      potential of denuded amniotic membrane as a surrogate niche for limbal stem cells
      but supports its suitability as a substrate to promote the formation of a well
      differentiated stratified corneal epithelial equivalent for tissue engineering
      strategies.

PMID- 22382595
TI  - Dry eye disease in patients with depressive and anxiety disorders in Shanghai.
AB  - PURPOSE: To investigate dry eye disease (DED) and risk factors in patients with
      depressive or anxiety disorders at a psychiatric clinic in China. METHODS: Cross
      sectional study. Subjects (>=16 years) who had depressive or anxiety disorders
      were evaluated with history, questionnaires (Self-rating Anxiety Scale, Self
      rating Depression Scale, and Ocular Surface Disease Index), and eye examination.
      RESULTS: There were 472 psychiatric patients in the study, including 176 patients
      (37%) with depression, 170 patients (36%) with generalized anxiety disorder, 60
      patients (13%) with depression and anxiety disorder, 55 patients (12%) with
      obsessive-compulsive disorder, and 11 patients (2%) with panic disorder. DED was
      present in 283 patients (60%). Compared with patients who did not have DED,
      patients with DED were significantly older, had longer duration of psychiatric
      disease and use of antianxiety or antidepressant medication, and more frequently
      were using a selective serotonin reuptake inhibitor (SSRI). Logistic regression
      analysis showed that older age, duration of psychiatric disorder, and use of an
      SSRI were significant independent predictors of the presence of DED. Older age,
      Self-rating Anxiety Scale >52, and use of tricyclic antidepressants were
      significant independent predictors of worse vision-targeted health-related
      quality of life (higher Ocular Surface Disease Index). CONCLUSIONS: DED is
      frequent in patients with depressive and anxiety disorders, especially patients
      who are older, have longer duration of psychiatric disorder, and use an SSRI.
      Psychiatric disorders and use of antidepressants should be considered in the
      differential diagnosis of DED.

PMID- 22382596
TI  - Volume targeted versus pressure support non-invasive ventilation in patients with
      super obesity and chronic respiratory failure: a randomised controlled trial.
AB  - INTRODUCTION: Automatic titration modes of non-invasive ventilation, including
      average volume assured pressure support (AVAPS), are hybrid technologies that
      target a set volume by automated adjustment of pressure support (PS). These
      automated modes could offer potential advantages over fixed level PS, in
      particular, in patients who are super obese. METHODS: Consecutive patients with
      obesity hypoventilation syndrome were enrolled in a two-centre prospective single
      blind randomised controlled trial of AVAPS versus fixed-level PS using a strict
      protocolised setup. MEASUREMENTS: The primary outcome was change in daytime
      arterial PCO(2) (PaCO(2)) at 3 months. Body composition, physical activity (7-day
      actigraphy) and health-related quality of life (severe respiratory insufficiency
      questionnaire, SRI) were secondary outcome measures. RESULTS: 50 patients (body
      mass index 50+/-7 kg/m(2); 55+/-11 years; 53% men) were enrolled with a mean
      PaCO(2) of 6.9+/-0.8 kPa and SRI of 53+/-17. 46 patients (23 AVAPS and 23 PS)
      completed the trial. At 3 months, improvements in PaCO(2) were observed in both
      groups (AVAPS 0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS 0.6 kPa, 95% CI 0.1 to
      1.1, p=0.02) but no between-group difference (-0.1 kPa, 95% CI -0.7 to 0.6,
      p=0.87). SRI also improved in both groups (AVAPS 11, 95% CI 6 to 17, p<0.001 vs
      PS 7, 95% CI 1 to 12, p=0.02; between groups 5, 95% CI -3 to 12, p=0.21).
      Secondary analysis of both groups combined showed improvements in daytime
      physical activity that correlated with reduction in fat mass (r=0.48; p=0.01).
      CONCLUSION: The study demonstrated no differences between automated AVAPS mode
      and fixed-level PS mode using a strict protocolised setup in patients who were
      super obese. The data suggest that the management of sleep-disordered breathing
      may enhance daytime activity and promote weight loss in super-obese patients.

PMID- 22382597
TI  - Basic science for the chest physician: Pseudomonas aeruginosa and the cystic
      fibrosis airway.

PMID- 22382598
TI  - Hepatopulmonary syndrome caused by sarcoidosis of the liver treated with
      transjugular intrahepatic portosystemic shunt.

PMID- 22382600
TI  - Sex, susceptibility to smoking and chronic obstructive pulmonary disease: the
      effect of different diagnostic criteria. Analysis of the Health Survey for
      England.
AB  - BACKGROUND: Some previous studies suggest there are sex differences in
      susceptibility to, and prevalence of, chronic obstructive pulmonary disease
      (COPD) but findings are inconsistent. In this study, whether different diagnostic
      criteria for COPD may contribute to these conflicting findings was examined.
      METHODS: Cross sectional analysis of data from the 1995, 1996 and 2001 Health
      Survey for England was undertaken, including participants of white ethnicity,
      aged 40+ years with a valid smoking history and lung function data. COPD was
      defined using Global Initiative for Chronic Obstructive Lung Disease (GOLD),
      National Institute for Health and Clinical Excellence (NICE) and lower limit of
      normal (LLN) spirometric criteria, in the absence of a diagnosis of asthma.
      RESULTS: COPD was present in 3035 (16.1%), 1304 (7.0%) and 1684 (9.0%) people,
      according to the GOLD, NICE and LLN criteria, respectively. With both the GOLD
      and NICE definitions, men had significant independent increased risks of COPD
      compared with women (OR 1.46 (95% CI 1.34 to 1.59) and 1.30 (1.15 to 1.48),
      respectively). With the LLN definition, this effect was removed (OR 0.96 (0.87 to
      1.07). With the use of both the GOLD and NICE criteria, women had significantly
      greater susceptibility to COPD (25-30% higher risk) for the same level of pack
      years of exposure. This was not observed with the LLN criteria. CONCLUSIONS: The
      study indicates that sex differences in risk of COPD reported in previous studies
      are influenced by the definition used for COPD. When using a statistically driven
      definition (LLN), no independent sex difference was found and there was no
      evidence of an increased susceptibility to COPD among female compared with male
      smokers.

PMID- 22382602
TI  - Comparison of estimators in nested case-control studies with multiple outcomes.
AB  - Reuse of controls in a nested case-control (NCC) study has not been considered
      feasible since the controls are matched to their respective cases. However, in
      the last decade or so, methods have been developed that break the matching and
      allow for analyses where the controls are no longer tied to their cases. These
      methods can be divided into two groups; weighted partial likelihood (WPL) methods
      and full maximum likelihood methods. The weights in the WPL can be estimated in
      different ways and four estimation procedures are discussed. In addition, we
      address modifications needed to accommodate left truncation. A full likelihood
      approach is also presented and we suggest an aggregation technique to decrease
      the computation time. Furthermore, we generalize calibration for case-cohort
      designs to NCC studies. We consider a competing risks situation and compare WPL,
      full likelihood and calibration through simulations and analyses on a real data
      example.

PMID- 22382603
TI  - Examining changes in cellular communication in neuroendocrine cells after noble
      metal nanoparticle exposure.
AB  - As nanoparticles enjoy increasingly widespread use in commercial applications,
      the potential for unintentional exposure has become much more likely during any
      given day. Researchers in the field of nanotoxicity are working to determine the
      physicochemical nanoparticle properties that lead to toxicity in an effort to
      establish safe design rules. This work explores the effects of noble metal
      nanoparticle exposure in murine chromaffin cells, focusing on examining the
      effects of size and surface functionality (coating) in silver and gold,
      respectively. Carbon-fibre microelectrode amperometry was utilized to examine the
      effect of exposure on exocytosis function, at the single cell level, and provided
      new insights into the compromised functions of cells. Silver nanoparticles of
      varied size, between 15 and 60 nm diameter, were exposed to cells and found to
      alter the release kinetics of exocytosis for those cells exposed to the smallest
      examined size. Effects of gold were examined after modification with two commonly
      used 'bio-friendly' polymers, either heparin or poly (ethylene glycol), and gold
      nanoparticles were found to induce altered cellular adhesion or the number of
      chemical messenger molecules released, respectively. These results support the
      body of work suggesting that noble metal nanoparticles perturb exocytosis,
      typically altering the number of molecules and kinetics of release, and supports
      a direct disruption of the vesicle matrix by the nanoparticle. Overall, it is
      clear that various nanoparticle physicochemical properties, including size and
      surface coating, do modulate changes in cellular communication via exocytosis.

PMID- 22382604
TI  - Early magnetic resonance imaging in acute knee injury: a cost analysis.
AB  - PURPOSE: Acute knee injury is common, and MRI is often only used when non
      operative management fails because of limited availability. We investigated
      whether early MRI in acute knee injury is more clinically and cost-effective
      compared to conventional physiotherapy and reassessment. METHODS: All patients
      with acute indirect soft tissue knee injury referred to fracture clinic were
      approached. Recruited patients were randomised to either the MRI group: early MRI
      within 2 weeks or the control group: conventional management with physiotherapy.
      Patients were assessed in clinic initially, at 2 weeks and 3 months post-injury.
      Management costs were calculated for all patients until surgical treatment or
      discharge. RESULTS: Forty-six patients were recruited: 23 in the MRI and 23 in
      the control group. Male sex and mean age were similar in the two groups. The
      total management cost of the MRI group was L16,127 and control group was L16,170,
      with a similar mean cost per patient (NS). The MRI group had less mean
      physiotherapy (2.5 +/- 1.9 vs. 5.1 +/- 3.5, p < 0.01) and outpatient appointments
      (NS). Median time to surgery and time off work was less in the MRI group (NS).
      The MRI group had less pain (p < 0.05), less activity limitation (p = 0.04) and
      better satisfaction (p = 0.04). CONCLUSIONS: Early MRI in acute knee injury
      facilitates faster diagnosis and management of internal derangement at a cost
      comparable to conventional treatment. Moreover, patients had significantly less
      time off work with improved pain, activity limitation and satisfaction scores.
      LEVEL OF EVIDENCE: II.

PMID- 22382605
TI  - Expression of the broad autism phenotype in simplex autism families from the
      Simons Simplex Collection.
AB  - The broad autism phenotype (BAP) refers to the phenotypic expression of an
      underlying genetic liability to autism, manifest in non-autistic relatives. This
      study examined the relationship among the Broad Autism Phenotype Questionnaire
      (BAPQ), Social Responsiveness Scale: Adult Research Version (SRS:ARV), and Family
      History Interview (FHI) in a large, multi-site study of 1,650 simplex families
      (Simons Simplex Collection). Correlations between the BAPQ and SRS:ARV Total
      scores were moderate, and correlations between FHI ratings and SRS:ARV and BAPQ
      were significant but weak. Overall, the results suggested that BAP traits occur
      at low rates in simplex families, and rates vary significantly depending upon the
      measure utilized. Implications include the need for multiple informants, and the
      assessment of distinct BAP traits in large-scale genetic studies of individuals
      with ASD. 

PMID- 22382606
TI  - Brief report: a comparison of statistical learning in school-aged children with
      high functioning autism and typically developing peers.
AB  - Individuals with autism spectrum disorders have impairments in language
      acquisition, but the underlying mechanism of these deficits is poorly understood.
      Implicit learning is potentially relevant to language development, particularly
      in speech segmentation, which relies on sensitivity to transitional probabilities
      between speech sounds. This study investigated the relationship between implicit
      learning and current language abilities in school-aged children with high
      functioning autism and a history of language delay (n = 17) and in children with
      typical development (n = 24) using a well-studied artificial language learning
      task. Results suggest that high functioning children with autism (HFA) and TD
      groups were equally able to implicitly learn transitional probabilities from a
      lengthy stimulus stream. Furthermore, task performance was not strongly
      associated with current language abilities. Implications for implicit learning
      research in HFA are discussed.

PMID- 22382608
TI  - SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is
      there any correlation with Parkinson's disease?
AB  - OBJECTIVES: The differential diagnosis between essential tremor (ET) and
      Parkinson's disease (PD) may be, in some cases, very difficult on clinical
      grounds alone. In addition, it is accepted that a small percentage of ET patients
      presenting symptoms and signs of possible PD may progress finally to a typical
      pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4
      iodophenyl) nortropane, also called FP-CIT, labelled with (123)I (commercially
      known as DaTSCAN) has been proven to be useful in the differential diagnosis
      between PD and ET and to confirm dopaminergic degeneration in patients with
      parkinsonism. The aim of this study is to identify dopaminergic degeneration in
      patients with PD and distinguish them from others with ET using semi-quantitative
      SPECT (123)I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV),
      in addition with the respective ones of patients referred as suffering from ET,
      as well as, of patients with a PD diagnosis at an initial stage with a unilateral
      presentation of motor signs. METHODS: Twenty-eight patients suffering from ET (10
      males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this
      study. In addition, 33 patients (11 males and 22 females) with an established
      diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right
      hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT
      images and measure the radiopharmaceutical uptake in the striatum (S), as well as
      the caudate nucleus (CN) and putamen (P) in all individuals. RESULTS: Qualitative
      (Visual) interpretation of the SPECT data did not find any difference in the
      uptake of the radiopharmaceutical at the level of the S, CN and P between NV and
      ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in
      the P of all PD patients. Semiquantitative analysis revealed significant
      differences between NV and ET patients in the striatum, reduced in the latter.
      There was also a significant reduction in the tracer accumulation in the left
      putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients
      with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right
      putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET
      at (so many months afterwards) revealed no significant change in clinical
      presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of
      them (so many months afterwards) was negative in all but one. This one had an
      equivocal baseline study which deteriorated 12 months later. CONCLUSIONS: Our
      results do not support the hypothesis of a link between essential tremor and
      Parkinson's disease. However, it appears that ET patients have a small degree of
      striatal dopaminergic degeneration. If this is due to alterations in the
      nigrostriatl pathway or of other origin it is not clear. Follow-up studies of
      essential tremor patients are warranted to assess progression of disease and to
      understand better the possible cause for striatal dopaminergic degeneration.

PMID- 22382607
TI  - Diagnostics and new developments in the treatment of ocular allergies.
AB  - About 30% of people suffer from allergic symptoms, and 40% to 80% of them have
      eye symptoms. Atopic conjunctivitis is divided into seasonal allergic
      conjunctivitis and perennial allergic conjunctivitis. The treatment of seasonal
      allergic conjunctivitis is simple: antihistamines, anti-inflammatory agents, or
      cromoglycate. Perennial allergic conjunctivitis needs longer therapy with mast
      cell stabilizers and sometimes local steroids. Atopic keratoconjunctivitis
      requires long-term treatment of the lid eczema and keratoconjunctivitis. Vernal
      keratoconjunctivitis mainly affects children and young people. It commonly calms
      down after puberty. It demands intensive therapy, often for many years, to avoid
      serious complicating corneal ulcers. Giant papillary conjunctivitis is a foreign
      body reaction in contact lens users or patients with sutures following ocular
      surgery. Nonallergic eosinophilic conjunctivitis affects mostly middle-aged and
      older women with eosinophilic conjunctivitis and dry eye. Contact allergic
      blepharoconjunctivitis is often caused by cosmetics and eye medication. Work
      related ocular allergies should be considered as a cause of resistant ocular
      symptoms in workplaces.

PMID- 22382609
TI  - A retrospective study on the transition of radiation dose rate and iodine
      distribution in patients with I-131-treated well-differentiated thyroid cancer to
      improve bed control shorten isolation periods.
AB  - OBJECTIVE: To evaluate for how long patients should be isolated after I-131
      treatment for thyroid cancer according to the guidelines issued by the Japanese
      Ministry of Welfare. METHODS: We reviewed 92 therapies performed in 76 patients
      who were administered I-131 at our hospital from July 2007 to September 2009.
      Fifty-six patients were given 2220 or 2960 MBq I-131 at the first therapy, and 29
      patients underwent 36 repeated therapies using 2960, 3700, 5550 or 7400 MBq I
      131. We surveyed radioactivity for a 1 cm dose equivalent rate at 1 m intervals
      at 30 and 48 h after administration of I-131, obtained planar scintigrams at 48
      h, and surveyed radioactivity repeatedly until it fell to under 30 MUSv/h.
      RESULTS: The radioactivity was under 30 MUSv/h at 30 h in 51 out of 92 cases
      (55%). Among the remaining 41 (45%) cases, 27 (29%) and 32 (35%) cases showed
      decreased radioactivity under 30 MUSv/h at 48 and 72 h, respectively, and it
      remained higher than 30 MUSv/h at 72 h in another 9 cases (10%). In 5 (38%) of
      the 13 cases with bone metastasis, the radioactivity remained over 30 MUSv/h
      after 72 h, and scintigrams showed strong accumulation in bone metastases. Among
      the 27 cases demonstrating below 30 MUSv/h at 48 h, 26 showed radioactivity being
      below 50 MUSv/h at 30 h, while it was above 50 MUSv/h at 30 h in all 14 cases
      which demonstrated above 30 MUSv/h at 48 h. We compared the radioactivity levels
      of 27 cases under 30 MUSv/h at 48 h and 14 cases over 30 MUSv/h at 48 h using a
      cutoff value of under 50 MUSv/h at 30 h to release patient at 48 h, the positive
      predictive value and negative predictive value were 100 and 93%, respectively,
      and radioactivity was found to differ significantly (P < 0.001). CONCLUSIONS: To
      predict external radiation levels at 48 h, it is helpful to consider external
      radiation levels at 30 h after treatment. Consideration of intracellular uptake
      in thyroid cancer, especially in cases of bone metastases, digestive tract
      function, and renal function, is important for predicting isolated period.

PMID- 22382610
TI  - Granulofilamentous meningioma.
AB  - A 55-year old female was referred to the Department of Neurosurgery, Kitasato
      Hospital, because of a hearing impairment. Neuroimaging revealed a typical
      meningioma attached to the falx in the right frontal region. During surgery, an
      encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the
      falx was completely removed by an interhemispheric approach. On light microscopy,
      many of the tumor cells contained eosinophilic inclusions with single or multiple
      vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were
      eccentric. There were no signs of malignancy in the specimen. Electron microscopy
      revealed that most of the eosinophilic inclusions were composed of filaments
      measuring 12 nm in diameter. There have been several reports of benign
      meningiomas with eosinophilic inclusions composed of intermediate filaments. The
      microscopic differences between these types of tumor and rhabdoid meningiomas are
      very subtle, and it is important the two types of tumors are not confused. Benign
      meningiomas with eosinophilic inclusions comprising intermediate filaments, for
      example the tumor described in this report, have been diagnosed as
      granulofilamentous meningiomas, which is a subtype of benign meningioma.

PMID- 22382611
TI  - Incretin-based therapies in clinical practice: from efficacy to effectiveness.
      Focus on liraglutide.
AB  - AIM: Liraglutide is a GLP-1 analogue introduced in Italy in 2010; its efficacy
      and safety have been tested within the comprehensive "LEAD program". The aim of
      this paper was to evaluate whether and to what extent routine practice outcomes
      are consistent with research findings. METHODS: One diabetes outpatient clinic
      reviewed data of patients receiving incretin-based therapies. Differences in
      characteristics of patients treated with liraglutide, exenatide, or DPP-IV
      inhibitors were evaluated. The subgroups of patients treated with liraglutide,
      exenatide or DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin) and
      followed for at least eight months were analyzed longitudinally. Hierarchical
      linear models for repeated measurements were applied to assess trends over time.
      RESULTS: Incretin-based treatments were prescribed to 312 patients (liraglutide:
      130, exe-natide: 72, DPP-IV inhibitors: 110). Diabetes duration, HbA1c levels,
      and BMI were substantially higher in exenatide and liraglutide groups than in the
      DPP-IV inhibitors group. Liraglutide was often administered in combination with
      metformin alone, while exenatide was often added to two or more drugs. Overall,
      20 (15.4%) liraglutide interruptions were recorded, especially due to nausea.
      Treatment drop out rate was higher in exenatide and DPP-IV inhibitors groups (in
      exenatide mostly for gastrointestinal side effects, in DPP-IV for inefficacy).
      After eight months, overall levels of HbA1c were reduced from 8.1+/-1.1 to 7.1+/
      0.8 (P<0.0001) with liraglutide. Furthermore, fasting blood glucose was reduced
      by 37.9+/-6.2 mg/dL (P<0.0001), body weight by 4.1+/-0.5 kg (P<0.0001), systolic
      blood pressure by 8.9+/-2.7 mmHg (P<0.001), total cholesterol by 8.8+/-4.1 mg/dL
      (P=0.04), and triglycerides by 24.4+/-14.6 mg/dL (P=0.07). Patients who had their
      therapy replaced at baseline from exenatide or DPP-IV had a further reduction in
      HbA1c, FBG and body weight. CONCLUSION: Liraglutide is penetrating diabetes care
      with results strictly mimicking the promising beneficial effects found in the
      LEAD program.

PMID- 22382612
TI  - Mitotane treatment for adrenocortical carcinoma: an overview.
AB  - Adrenocortical carcinoma (ACC) is a rare aggressive endocrine neoplasm
      characterized by a 5-year survival of less than 50%. Due to the widespread use of
      imaging techniques in clinics, ACC is increasingly recognized as an incidentally
      discovered tumor. Mostly characterized by poor prognosis, ACC is often diagnosed
      at an advanced stage of disease. Early diagnosis is uncommon; when diagnosed,
      ACCs are usually large and have invaded adjacent organs, even if metastatic
      spread to distant sites can be absent. Complete surgical resection is the only
      potentially curative treatment for patients with localized disease; however, due
      to a recurrence rate of 50-70% after apparent radical surgery, there is a strong
      rationale for a concomitant systemic treatment. Adrenolytic therapy with mitotane
      (o,p>-DDD), administered alone or in combination with others antineoplastic
      agents, is the primary treatment for patients with advanced ACC and is
      increasingly used also in an adjuvant setting, even if controversy exists on this
      issue due to the limitations of the available literature. Despite being in use
      for many years, the rarity of ACC precluded the organization of randomized
      trials; thus, many areas of uncertainty and controversy remain regarding the role
      of this old drug in the clinical management of patients with ACC. The purpose of
      this paper is to review the current evidence on mitotane treatment in patients
      with advanced disease and in ACC patients after complete surgical resection as
      adjuvant treatment.

PMID- 22382613
TI  - Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient:
      the role of metformin.
AB  - Metformin is a widely used and extensively studied insulin sensitising drug for
      the treatment of women with polycystic ovary syndrome (PCOS), with various
      actions in tissues responding to insulin that include the liver, skeletal muscle,
      adipose tissue, the endothelium of blood vessels, and the ovaries. Treatment of
      PCOS women with metformin has been shown to reduce fasting glucose levels, blood
      pressure, and serum androgens; further effects of metformin in women with PCOS
      may include direct effects on the central nervous system; and indirect effects
      via the modification of gut hormone and adipokine synthesis and/or secretion. A
      number of "novel" adipokines and metabolic factors have been recently identified
      which may play a role both in the pathogenesis and the treatment of women with
      PCOS. We here discuss recent advances in the area, with a focus on neuroendocrine
      and endocrine dysfunctions in women with PCOS and the potential role of metformin
      in this context.

PMID- 22382614
TI  - Ovarian aging and implications for fertility female health.
AB  - Ovarian aging is a major detrimental factor of pregnancy achievement and it is
      related to other issues of women's health. The purpose of this review is to
      present an update on ovarian aging risk factors followed by contemporary methods
      of its assessment and an overview of its current management strategies in
      assisted reproductive technologies (ART). Ovarian aging is a multifactorial trait
      governed by several factors including medical, lifestyle, genetic, autoimmune and
      idiopathic. There are several established risk factors and many others that are
      still being revealed. Heritability has a major influence on ovarian aging.
      Different genetic strategies and approaches for ovarian aging evaluation have
      been rapidly expanding; however the mission is far from complete. Genome-wide
      association studies seems to be the most applicable to advance this research.
      Although anti-Mullerian hormone and antral follicle count (AFC) biomarkers seems
      to be the most reliable predictors of ovarian aging, none has demonstrated
      conclusive evidence to predict pregnancy achievement in an ART setting. The
      debate continues which of the two predictors is the most suitable in ART as well
      as non-ART settings. Although multivariate models have been shown to be equally
      predictive to AFC, latest data support the notion that chronological age and
      genetic markers inclusion may increase their reliability. Several strategies have
      been suggested to manage ovarian aging in ART settings. None of the stimulation
      protocols or ART interventions has been shown to be convincingly beneficial to
      ovarian aging women and individualization of treatment is still recommended.
      Ovarian priming by different androgen preparations has been shown to be promising
      but more randomized controlled studies are required to substantiate these
      findings. Except for oocyte donation other ART strategies have not shown a
      persuasive evidence for advanced ovarian aging infertility patients. The new
      development of oocyte vitrification may well introduce opportunities for
      fertility preservation to woman at risk. It is concluded that proper assessment
      and detection of ovarian aging, employing current or developing biomarkers of
      ovarian reserve, may enable health providers to recommend, at appropriate
      biological time, early pregnancy achievement or fertility preservation in women
      at risk.

PMID- 22382615
TI  - Breast cancer risk during hormone therapy: experimental versus clinical data.
AB  - Evidence is increasing suggesting that adding progestogens to estrogens can
      increase the risk of breast cancer. However, our experimental data as a result of
      scientific collaboration between university of Tuebingen, Germany, and university
      of Beijing, China, comparing all available progestogens used in hormone therapy
      and hormonal contraception present high evidence that there may be differences
      regarding breast cancer risk. Especially of concern may be to differentiate
      between primary and secondary risk i.e. between the effect of on benign and
      malignant breast epithelial cells suggesting differences in primary risk and risk
      in patients after breast cancer. Of importance also is that in contrast to
      natural progesterone the apocrine impact of stromal growth factors and also
      certain cell components of breast epithelial cells can strongly increase
      proliferation rates of some (but not all. synthetic progestogens which can lead
      to clinical cancer before (in contrast to estrogen-only therapy.
      carcinoprotective mechanisms can work. Regarding clinical data, epidemiological
      studies and especially the Women's Health Initiative, so far the only prospective
      placebo-controlled study, demonstrate an increased risk under combined
      estrogen/progestogen-, but not under estrogen-only therapy. However, up to now
      the clinical studies cannot discriminate between the various progestogens mostly
      due to too small patient numbers in the subgroups, and in most studies either
      medroxyprogesterone acetate or norethisterone have been used. However, there is
      evidence that the natural progesterone and dydrogesterone, possibly also the
      transdermal usage of synthetic progestogens, may have less risks, but this must
      be proven in further clinical trials.

PMID- 22382616
TI  - Anomalies in the inflammatory response in endometriosis and possible
      consequences: a review.
AB  - Defined by the presence of endometrial-like cells outside the uterus,
      endometriosis is one of the most diagnosed gynecological disorders, affecting 5
      to 10 % of reproductive age women, but the true incidence is unknown.
      Endometriosis is a major cause of pelvic pain, dysmenorrhea, dyspareunia,
      infertility and menstrual irregularities, but there is no clear correlation
      between the symptoms and the extent of the disease. Despite decades of intensive
      investigations, little is known about the pathogenesis of endometriosis. The
      disease is often associated with chronic pelvic inflammation. Abnormal levels of
      immune cells such macrophages, dendritic and natural killer cells were found in
      the peritoneal cavity of patients. However these cells seem to be unable to
      detect and eliminate ectopic endometrial cells. Several studies showed that
      peritoneal immune cells are dysfunctional and may rather contribute to
      endometriosis development. A review of relevant clinical and scientific studies
      was carried out. This review sheds light on cellular and immunological pro
      inflammatory changes which were observed in patients with endometriosis, their
      impact on angiogenesis, apoptosis, extracellular matrix remodeling and hormonal
      production and consequences on fertility.

PMID- 22382617
TI  - Menopausal obesity and metabolic syndrome - PolSenior study.
AB  - Obesity is a common problem and its health consequences depend on the phenotype
      of obesity. Clinical aspects of three phenotypes of obesity: upper body
      (visceral), lower body (healthy) and metabolic obesity with normal weight are
      discussed. The PolSenior study and other data show that the incidence of obesity
      increases during hormonal climacteric transformation with special emphasis on
      visceral (72%) and metabolic obesity with normal weight (16%). The etiology of
      menopausal obesity and fat redistribution with an increase incidence of
      menopausal metabolic syndrome is presented. The role of sex hormones and SHBG of
      fat mass and fat distribution in postmenopausal women is discussed on the basis
      of PolSenior study. The diagnostic-therapeutic algorithm for climacteric women is
      recommended according to cardiovascular diseases risk (CVD), elevated waist
      circumference, serum triglicerides, decreased HDL cholesterol, elevated fasting
      glucose, HOMA over 1.69 and BP over 130/80 mmHg. In women with CVD risk factors
      the metformin therapy is a golden standard.

PMID- 22382618
TI  - Tumor dosimetry using [124I]m-iodobenzylguanidine microPET/CT for [131I]m
      iodobenzylguanidine treatment of neuroblastoma in a murine xenograft model.
AB  - PURPOSE: [(124)I]m-iodobenzylguanidine ((124)I-mIBG) provides a quantitative tool
      for pretherapy tumor imaging and dosimetry when performed before [(131)I]m
      iodobenzylguanidine ((131)I-mIBG) targeted radionuclide therapy of neuroblastoma.
      (124)I (T (1/2) = 4.2 days) has a comparable half-life to that of (131)I (T (1/2)
      = 8.02 days) and can be imaged by positron emission tomography (PET) for accurate
      quantification of the radiotracer distribution. We estimated expected radiation
      dose in tumors from (131)I-mIBG therapy using (124)I-mIBG microPET/CT imaging
      data in a murine xenograft model of neuroblastoma transduced to express high
      levels of the human norepinephrine transporter (hNET). PROCEDURES: In order to
      enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691)
      human neuroblastoma cells were engineered to express high levels of hNET protein
      by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were
      implanted subcutaneously and into renal capsules in athymic mice. (124)I-mIBG
      (4.2-6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time
      points over 95 h (0.5, 3-5, 24, 48, and 93-95 h median time points). In vivo
      biodistribution data in normal organs, tumors, and whole-body were collected from
      reconstructed PET images corrected for photon attenuation using the CT-based
      attenuation map. Organ and tumor dosimetry were determined for (124)I-mIBG. Dose
      estimates for (131)I-mIBG were made, assuming the same in vivo biodistribution as
      (124)I-mIBG. RESULTS: All NB1691-hNET tumors had significant uptake and retention
      of (124)I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable
      mIBG uptake in vivo, despite in vitro uptake. (124)I-mIBG with microPET/CT
      provided an accurate three-dimensional tool for estimating the radiation dose
      that would be delivered with (131)I-mIBG therapy. For example, in our model
      system, we estimated that the administration of (131)I-mIBG in the range of 52.8
      206 MBq would deliver 20 Gy to tumors. CONCLUSIONS: The overexpression of hNET
      was found to be critical for (124)I-mIBG uptake and retention in vivo. The
      quantitative (124)I-mIBG PET/CT is a promising new tool to predict tumor
      radiation doses with (131)I-mIBG therapy of neuroblastoma. This methodology may
      be applied to tumor dosimetry of (131)I-mIBG therapy in human subjects using
      (124)I-mIBG pretherapy PET/CT data.

PMID- 22382619
TI  - Suboptimal health as a predictor of non-permanent employment in middle age: a 12
      year follow-up study of the Northern Swedish Cohort.
AB  - PURPOSE: Earlier research on health-related selection in the labour market has
      concentrated on selection of those with poor health into unemployment. The
      purpose of the present study was to investigate if suboptimal health also
      predicts non-permanent employment. METHODS: A population cohort of 517 men and
      477 women was surveyed at age 30 and at age 43 about their health and yearly
      employment. Non-permanent employment during the follow-up was assessed for its
      occurrence with Cox regression and for the amount (accumulation in months) with
      generalised linear models. RESULTS: Suboptimal self-rated health, sense
      functioning and sleep quality in women and suboptimal mood in men predicted high
      accumulation of non-permanent employment. By contrast, in men, suboptimal self
      rated health and sense functioning predicted low accumulation. The gender
      differences were statistically significant. Smoking predicted high occurrence and
      accumulation of non-permanent employment equally in men and women, whereas no
      associations were seen with overweight and alcohol consumption. CONCLUSIONS:
      Selection into non-permanent employment was shown for several indicators of
      suboptimal health. A gendered pattern was found, with more health selection among
      women. The findings of this pioneering study should be tested with further
      research.

PMID- 22382620
TI  - Properties of IRMOF-14 and its analogues M-IRMOF-14 (M = Cd, alkaline earth
      metals): electronic structure, structural stability, chemical bonding, and
      optical properties.
AB  - The chemical bonding, electronic structure, and optical properties of the
      experimentally available metal-organic framework IRMOF-14 and its metal
      substituted analogues M-IRMOF-14 (M = Zn, Cd, Be, Mg, Ca, Sr, Ba), which contain
      a pyrene-2,7-dicarboxylate linker group, have been systematically investigated
      using DFT calculations. The unit cell volume and atomic positions were optimized
      with the Perdew-Burke-Ernzerhof (PBE) functional and showed good agreement
      between experimental and theoretical equilibrium structural parameters for Zn
      IRMOF-14. The calculated bulk moduli indicate that the whole M-IRMOF-14 series
      are soft materials. The estimated band gap from DOS calculations for the M-IRMOF
      14 series is ca. 2.5 eV, essentially independent of the metal ion and indicative
      of nonmetallic character. The band gap value is distinctly different from those
      calculated previously for the M-IRMOF-1 (benzene-1,4-dicarboxylate linker; ca.
      3.5 eV) and M-IRMOF-10 (biphenyl-4,4'-dicarboxylate linker; ca. 3.0 eV) series
      and this confirms that the identity of the linker is a key parameter to control
      band gaps in an isoreticular series of main-group MOFs. In view of potential uses
      of MOFs in organic semiconducting devices such as field-effect transistors, solar
      cells, and organic light-emitting devices, the linear optical properties of these
      materials were also investigated. Comparisons are made with the M-IRMOF-1 and M
      IRMOF-10 series.

PMID- 22382621
TI  - Tuning the reduction power of supported gold nanoparticle photocatalysts for
      selective reductions by manipulating the wavelength of visible light irradiation.
AB  - Gold nanoparticles supported on CeO(2) were found to be efficient photocatalysts
      for three selective reductions of organic compounds at ambient temperatures,
      under irradiation of visible light; their reduction ability can be tuned by
      manipulating the irradiation wavelength.

PMID- 22382622
TI  - [Motion analysis of target during stereotactic radiotherapy of lung tumors using
      volumetric modulated arc therapy].
AB  - Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated
      radiotherapy (IMRT) technique capable of acquiring projection images for cone
      beam computed tomography (CBCT). Respiratory-correlated cone-beam computed
      tomography, namely 4D-CBCT, serves to assess the displacement of a tumor position
      between planning and treatment due to organ motion and respiration, and is
      important for more accurate radiation therapy. On the other hand, recently, a 320
      detector row CT scanner, namely 4D-CT, has become available that allows axial
      volumetric scanning of a 16-cm-long range in a patient without table movement.
      The goal of our research is to establish a new method of verification during
      treatment in stereotactic body radiotherapy. In this study, we compare the
      movement of the tumor between "before treatment" using 4D-CT and "in treatment"
      using 4D-CBCT. Three patients (55-68 years of age) with lung tumors underwent CT
      scans for radiotherapy planning using 4D-CT scans to analyze the movement of the
      tumor before treatment. The patients were treated by VMAT while acquiring
      projection images. 4D-CBCT datasets were reconstructed from the projection images
      using in-house programs. The tumor positions in 4D-CT and 4D-CBCT were detected
      and the movement of the tumor between "before treatment" and "in treatment" was
      similar. The movement of the tumors during treatment was predictable from 4D-CT
      before treatment. Furthermore, 4D-CBCT clarified the tumor position during
      treatment and could reevaluate the actual tumor position and dose distribution.
      We have successfully shown the movement of the tumor between "before treatment"
      using 4D-CT and "in treatment" using 4D-CBCT.

PMID- 22382623
TI  - [Cone-beam computed tomography-derived adaptive radiotherapy].
AB  - The purpose of this study was to evaluate the reliability of cone-beam computed
      tomography (CBCT)-derived adaptive radiotherapy. We evaluate planning computed
      tomography (pCT) and CBCT in 50 patients who had undergone image guided
      radiotherapy (IGRT) with CBCT. Irradiated sites included head, neck, chest,
      abdomen, and pelvis; there were 10 patients in each group. Treatment plans
      including 153 beam data were recalculated based on CBCT. To compare between pCT
      and CBCT, we estimated CT values of normal tissues, body contour, effective
      depth, and monitor units (MU) calculation. The maximum difference in CT values
      was observed in lung estimation. The 5 mm or more differences in depth were
      observed in 2 beams of 2 pelvic cases, but CBCT also demonstrated a shift of
      abdominal wall due to intestinal motility. There were downward trends for the
      effective depth and MU based on CBCT, especially in lung cases. However, the
      differences in prescribed dose due to MU calculation were less than 5% because
      all patients were treated with a multifield irradiation plan. CBCT provides not
      only precise daily setup but also accurate anatomical information on body
      contour. In addition, CBCT may be considered as a useful tool for dose
      calculation.

PMID- 22382624
TI  - [A method for removing moire artifacts from scanned images of radiochromic films:
      application to transmissive scanning].
AB  - Dose verification using radiochromic films may bring about moire artifacts during
      the film scanning process using a flatbed scanner. A method for removing the
      moire artifacts was already reported for reflective scanning. Recently,
      transmissive scanning using EBT2 films has played a major role for dose
      verification in intensity-modulated radiation therapy. It was found that placing
      a nonreflecting glass plate on the detector side could eliminate all the moire
      artifacts for transmissive scanning.

PMID- 22382625
TI  - [Optimization of multi-leaf collimator leaf offset table for a treatment planning
      system].
AB  - For accurate dose delivery using a rounded leaf-end multi-leaf collimator (MLC),
      a consistent understanding of MLC leaf offset is required between a linear
      accelerator (linac) controller and a treatment planning system (TPS). We have
      found that the leaf offset tables were inconsistent between an Elekta linac
      controller and a Pinnacle TPS. An optimum leaf offset table for Pinnacle was
      determined by operating the TPS and the linac controller. It was suggested that
      the MLC leaf transmission value and the MLC leaf offset table stored in Pinnacle
      may need to be revised to improve dose verification results for volumetric
      modulated arc therapy.

PMID- 22382626
TI  - [Participating report of English presentation support seminar].

PMID- 22382627
TI  - [Recommendation of an oral presentation in international conferences held in
      Asian countries].

PMID- 22382628
TI  - [First Forum on JIRA Medical Imaging System Industry].

PMID- 22382629
TI  - Sexual relationship power and malnutrition among HIV-positive women in rural
      Uganda.
AB  - Inequality within partner relationships is associated with HIV acquisition and
      gender violence, but little is known about more pervasive effects on women's
      health. We performed a cross-sectional analysis of associations between sexual
      relationship power and nutritional status among women in Uganda. Participants
      completed questionnaires and anthropometric measurements. We assessed sexual
      relationship power using the Sexual Relationship Power Scale (SRPS). We performed
      logistic regression to test for associations between sexual relationship power
      and poor nutritional status including body mass index, body fat percentage, and
      mid-upper arm circumference. Women with higher sexual relationship power scores
      had decreased odds of low body mass index (OR 0.29, p = 0.01), low body fat
      percentage (OR 0.54, p = 0.04), and low mid-upper arm circumference (OR 0.22, p =
      0.01). These relationships persisted in multivariable models adjusted for
      potential confounders. Targeted interventions to improve intimate partner
      relationship equality should be explored to improve health status among women
      living with HIV in rural Africa.

PMID- 22382630
TI  - Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer
      cells.
AB  - BACKGROUND: Drug resistance in colorectal cancers is assumed to be mediated by
      changes in the expression of microRNAs, but the specific identities and roles of
      microRNAs are largely unclear. We examined the effect of 5-fluorouracil (5-FU)
      resistance on microRNA expression. METHODS: Two types of 5-FU-resistant colon
      cancer cells were derived from the DLD-1 and KM12C cell lines. The expressions of
      microRNAs were profiled with a microarray containing 723 microRNAs and validated
      by quantitative real-time polymerase chain reaction (qRT-PCR). To survey the
      downstream mediators of microRNA, we used a microRNA:mRNA immunoprecipitation
      (RIP)-Chip and pathway analysis tool to identify potential direct targets of
      microRNA. RESULTS: In response to 5-FU, miR-19b and miR-21 were over-expressed in
      5-FU-resistant cells. Of note, miR-19b was up-regulated 3.47-fold in the DLD-1
      resistant cells, which exhibited no alteration in cell cycle profiles despite
      exposure to 5-FU. After transfection of miR-19b, specific mRNAs were recruited to
      microRNA:mRNA complexes isolated with Ago2 antibody and subjected to whole-genome
      transcriptional analysis. In this analysis, 66 target mRNAs were enriched by at
      least 5.0-fold in the microRNA:mRNA complexes from DLD-1 resistant cells.
      Ingenuity pathway analysis of mRNA targets significantly (P < 0.05) indicated the
      category "Cell Cycle" as a probable area of the molecular and cellular function
      related with 5-FU resistance. Among candidate mRNA targets, SFPQ and MYBL2 have
      been linked to cell cycle functions. CONCLUSIONS: We revealed up-regulation of
      miR-19b in response to 5-FU and potential targets of miR-19b mediating the cell
      cycle under treatment with 5-FU. Our study provides an important insight into the
      mechanism of 5-FU resistance in colorectal cancers.

PMID- 22382631
TI  - Serum vascular endothelial growth factor as a predictor of response and survival
      in patients with advanced hepatocellular carcinoma undergoing hepatic arterial
      infusion chemotherapy.
AB  - BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been recognized as
      a useful therapeutic modality for patients with advanced hepatocellular carcinoma
      (HCC). The aim of this study was to investigate the association between serum
      vascular endothelial growth factor (VEGF) levels and the therapeutic effect of
      HAIC and the survival of patients undergoing HAIC. METHODS: Seventy-one patients
      with advanced HCC underwent HAIC through a subcutaneously implanted infusion
      port. One chemotherapy course consisted of low-dose cisplatin (10 mg/body on days
      1-5) and 5-fluorouracil (250 mg/body on days 1-5), and 1 treatment cycle
      consisted of 2-3 courses of chemotherapy. Serum VEGF levels were measured with
      the Bio-Plex Suspension Array System (Bio-Rad Laboratories). RESULTS: The median
      survival time (MST) of all patients was 10.2 months, and the 1-, 2-, 3-, and 5
      year survival rates were 46.5, 21.9, 12.8, and 3.7%, respectively. Of the 71
      patients, 3 achieved a complete response (CR) and 22 achieved a partial response
      (PR) [response rate (CR + PR/71) = 35%]. The serum VEGF level (>=100 pg/mL, P =
      0.026) was an independent predictor of therapeutic effect, and was positively
      correlated with the platelet count (r = 0.569, P < 0.001) and tumor size (r =
      0.543, P < 0.001). Child-Pugh class (P = 0.046), serum VEGF level (P = 0.004),
      and therapeutic effect (P = 0.005) were identified by multivariate analysis as
      independent predictors of survival. CONCLUSIONS: These results demonstrate that
      the serum VEGF level in patients with advanced HCC undergoing HAIC is an
      important predictive factor for therapeutic effect and survival.

PMID- 22382632
TI  - Effects of family history on inflammatory bowel disease characteristics in
      Japanese patients.
AB  - BACKGROUND: Although the prevalence of inflammatory bowel disease (IBD) is
      reported to have reached a plateau in Western countries, it is increasing in
      Asia. The etiology of IBD is still under investigation. We performed an
      epidemiological study to clarify the characteristics of IBD in Japan, focusing on
      patients' family history. METHODS: We obtained clinical data on ulcerative
      colitis (UC) (46,114 cases) and Crohn's disease (CD) (11,305 cases) in 2007 from
      an electronic database maintained under the Japanese Ministry of Health, Labour
      and Welfare's nationwide registry system, and analyzed the differences in disease
      characteristics between patients with IBD who had a family history of the disease
      and those who did not. RESULTS: A total of 2.7% of the patients with UC and 2.6%
      of those with CD had a family history. The present age and age at disease onset
      were lower among the patients with UC who had a family history than among those
      without (present age: p < 0.001; age at disease onset: p < 0.001; Mann-Whitney U
      test), but no similar trend was observed in the patients with CD. Disease
      severity was worse among both the UC and CD patients with a family history. The
      clinical course of patients with UC was not affected by family history. Levels of
      independence in daily life were associated with family history among CD patients,
      whereas age was associated with levels of independence in daily life among UC
      patients. CONCLUSION: Disease characteristics of IBD vary in some aspects
      according to the presence or absence of a family history.

PMID- 22382633
TI  - Randomized trial of peginterferon alpha-2a plus ribavirin versus peginterferon
      alpha-2b plus ribavirin for chronic hepatitis C in Japanese patients.
AB  - BACKGROUND: Pegylated interferon (PegIFN) plus ribavirin is the standard therapy
      for patients with chronic hepatitis C genotype 1. Although several randomized
      clinical trials have compared PegIFNalpha-2a with PegIFNalpha-2b, these 2
      regimens have not been directly compared in Asian patients. We, therefore,
      compared the safety and antiviral efficacy of these agents in Japanese patients.
      METHODS: A total of 201 PegIFN-naive, chronic hepatitis C patients were randomly
      assigned to once-weekly PegIFNalpha-2a (180 MUg) or PegIFNalpha-2b (60-150 MUg)
      plus ribavirin. We compared the sustained virological response (SVR) rates
      between the 2 regimens and analyzed their effects in relation to baseline
      characteristics, including single nucleotide polymorphisms (SNPs) near the
      interleukin-28B (IL28B) gene (rs8099917). RESULTS: PegIFNalpha-2a was associated
      with a higher SVR rate than PegIFNalpha-2b (65.3 vs. 51.0%, P = 0.039).
      PegIFNalpha-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36;
      95% confidence interval [CI] 1.19-15.50, and odds ratio 7.31; 95% CI 3.45-4.68,
      respectively) in logistic regression analysis. PegIFNalpha-2a was more effective
      than PegIFNalpha-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients,
      despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs.
      35.9%). Patients weighing <60 kg, women, and patients aged >60 years had
      significantly higher SVR rates with PegIFNalpha-2a than with PegIFNalpha-2b
      (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively). CONCLUSIONS:
      PegIFNalpha-2a plus ribavirin resulted in higher SVR rates than PegIFNalpha-2b
      plus ribavirin in Japanese patients. PegIFNalpha-2a-based treatment should
      therefore be the preferred choice for women, older or low-weight patients, and
      those with the IL28B TT genotype.

PMID- 22382636
TI  - Electrospinning synthesis and luminescence properties of one-dimensional
      La(9.33)(SiO4)6O2: Ln3+ (Ln = Ce, Eu, Tb) microfibers.
AB  - One-dimensional La(9.33)(SiO(4))(6)O(2): Ln(3+) (Ln = Ce, Eu, Tb) microfibers
      were fabricated by a simple and cost-effective electrospinning method. X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), high
      resolution transmission electron microscopy (HRTEM), photoluminescence (PL) and
      low voltage cathodoluminescence (CL) as well as kinetic decay were used to
      characterize the resulting samples. SEM and TEM results indicated that the
      diameter of the microfibers annealed at 1000  degrees C for 3 h was 200-245 nm.
      The microfibers were further composed of fine and closely linked nanoparticles.
      La(9.33)(SiO(4))(6)O(2): Ln(3+) (Ln = Ce, Eu, Tb) phosphors showed the
      characteristic emission of Ce(3+) (5d -> 4f), Eu(3+) ((5)D(0)->(7)F(J)) and
      Tb(3+) ((5)D(3,4)->(7)F(J)) under ultraviolet excitation and low-voltage electron
      beams (3-5 kV) excitation. An energy transfer from Ce(3+) to Tb(3+) was observed
      in the La(9.33)(SiO(4))(6)O(2): Ce(3+), Tb(3+) phosphor under ultraviolet
      excitation and low-voltage electron beam excitation. Luminescence mechanisms were
      proposed to explain the observed phenomena. Blue, red and green emission can be
      realized in La(9.33)(SiO(4))(6)O(2): Ln(3+) (Ln = Ce, Eu, Tb) microfibers by
      changing the doping ions. So the La(9.33)(SiO(4))(6)O(2): Ln(3+) (Ln = Ce, Eu,
      Tb) phosphors have potential applications in full-color field emission displays.

PMID- 22382634
TI  - H. pylori eradication did not improve dysregulation of specific oncogenic miRNAs
      in intestinal metaplastic glands.
AB  - BACKGROUND: Many microRNAs (miRNAs) are differentially expressed in Helicobacter
      pylori-infected gastric mucosa and in gastric cancer tissue. AIM: We aimed to
      compare the effect of H. pylori eradication on gastric mucosal miRNAs in subjects
      in a high-risk group for gastric cancer compared to controls. METHODS: Patients
      with a recent history of endoscopic resection for early gastric cancer and sex-
      and age-matched non-cancer controls were enrolled. The expression of 21 miRNAs
      was examined using gastric mucosal biopsy specimens and microdissected gastric
      glands from the lesser and greater curvatures of the gastric corpus both before
      and one year after H. pylori eradication. RESULTS: Twenty patients and 14
      controls were enrolled. The expression of oncogenic miRNAs (miR-17/92 and the miR
      106b-93-25 cluster, miR-21, miR-194, and miR-196) was significantly higher in the
      gastric mucosa of the cancer group than in the controls. H. pylori eradication
      resulted in a significant fall in the expression of oncogenic miRNAs only in the
      controls, whereas miR-223 expression was decreased and let-7d expression was
      increased in both groups. miR-196 was expressed only in intestinal metaplastic
      glands. The expression of oncogenic miRNAs was significantly higher in the
      intestinal metaplastic glands than in the non-intestinal metaplastic glands
      irrespective of H. pylori eradication. In neither group did H. pylori eradication
      significantly change any miRNA expression in the intestinal metaplastic glands.
      CONCLUSION: Dysregulation of specific miRNAs is present in H. pylori-induced
      corpus gastritis. H. pylori eradication improved miRNA dysregulation, but not in
      intestinal metaplastic glands or in the gastric mucosa of patients in a high-risk
      group for gastric cancer.

PMID- 22382637
TI  - Lamin misexpression upregulates three distinct ubiquitin ligase systems that
      degrade ATR kinase in HeLa cells.
AB  - Lamins are the major structural components of the nucleus and mutations in the
      human lamin A gene cause a number of genetic diseases collectively termed
      laminopathies. At the cellular level, lamin A mutations cause aberrant nuclear
      morphology and defects in nuclear functions such as the response to DNA damage.
      We have investigated the mechanism of depletion of a key damage sensor, ATR
      (Ataxia-telangiectasia-mutated-and-Rad3-related) kinase, in HeLa cells expressing
      lamin A mutants or lamin A shRNA. The degradation of ATR kinase in these cells
      was through the proteasomal pathway as it was reversed by the proteasomal
      inhibitor MG132. Expression of lamin A mutants or shRNA led to transcriptional
      activation of three ubiquitin ligase components, namely, RNF123 (ring finger
      protein 123), HECW2 (HECT domain ligase W2) and the F-box protein FBXW10. Ectopic
      expression of RNF123, HECW2 or FBXW10 directly resulted in proteasomal
      degradation of ATR kinase and the ring domain of RNF123 was required for this
      degradation. However, these ligases did not alter the stability of DNA-dependent
      protein kinase, which is not depleted upon lamin misexpression. Although
      degradation of ATR kinase was reversed by MG132, it was not affected by the
      nuclear export inhibitor, leptomycin B, suggesting that ATR kinase is degraded
      within the nucleus. Our findings indicate that lamin misexpression can lead to
      deleterious effects on the stability of the key DNA damage sensor, ATR kinase by
      upregulation of specific components of the ubiquitination pathway.

PMID- 22382638
TI  - Modified high-density lipoprotein modulates aldosterone release through scavenger
      receptors via extra cellular signal-regulated kinase and Janus kinase-dependent
      pathways.
AB  - Patients with type 2 diabetes (T2D) manifest significant abnormalities in
      lipoprotein structure and function. The deleterious impact of oxidative and
      glycoxidative modifications on HDL-mediated atheroprotective, antiinflammatory,
      and antioxidative phenomena has been well established. However, the biological
      effects of modified HDL on adrenal steroidogenesis-which could reveal a
      pathophysiological link to the overactivity of the renin-angiotensin-aldosterone
      system and its adverse cardiovascular consequences often observed in T2D-are not
      well delineated. We studied the role of modified HDL on aldosterone release from
      adrenocortical carcinoma cells (NCI-H295R). In vitro modifications of native HDL
      were performed in the presence of glucose for glycoxidized HDL (glycoxHDL) and
      sodium hypochlorite for oxidized HDL. Angiotensin II (AngII)-sensitized H295R
      cells were treated with lipoproteins for 24 h, and supernatant was used to
      measure aldosterone release. Both native and modified HDL augmented the steroid
      release from AngII-sensitized cells, with glycoxHDL having the greatest impact.
      Both the modified forms of HDL induced a significant increase in scavenger
      receptor expression and employed protein kinase C as well as extracellular signal
      regulated kinase as downstream effectors of aldosterone release. Native HDL and
      modified HDL required Janus kinase-2 for combating increased demand in
      steroidogenesis. Therefore, our data support the hypothesis that diabetes-induced
      modification of HDL may promote adrenocortical aldosterone secretion via
      different signal transduction pathways. This significant influence on multiple
      signaling mechanisms could be targeted for future research to implement novel
      therapeutic trials.

PMID- 22382639
TI  - Chemotherapy-induced cardiotoxicity.
AB  - Anthracycline-based chemotherapeutics have long been recognized as effective
      agents for treating a wide range of malignancies. However, their use is not
      without significant adverse cardiotoxic side effects. Strategies for prevention
      involve limiting free-radical production and subsequent cardiac myocyte damage.
      Dexrazoxane remains the most widely studied cardioprotective medication.
      Alternative agents may reduce cardiotoxicity but may still cause significant
      cardiovascular problems. The role of beta-blockers and angiotensin-converting
      enzyme inhibitors in the treatment of heart failure is well proven. The role of
      these medications in the prevention and treatment of chemotherapy-induced
      cardiotoxicity is not well established.

PMID- 22382640
TI  - Constitutional complex chromosomal rearrangements in a klinefelter patient: case
      report and review of literature.
AB  - BACKGROUNDS: While XXY aneuploidy is the most common disorder of sex chromosomes
      in men, complex chromosomal rearrangements (CCRs) are rare in humans. CASE
      DESCRIPTION: Here we describe clinical and cytogenetic findings in a male
      referred to our cytogenetic laboratory by an infertility clinic. The patient's
      age was 35 at the time of referral. Total azoospermia was confirmed on semen
      analysis. RESULTS: The karyotype of peripheral blood showed
      47,XXY,t(1;3;5)(p22;q29;q22). The mother had the same CCRs. DISCUSSION: To our
      best of our knowledge this is the first case of 47,XXY with CCRs. We think it is
      important to report such a unique chromosomal occurrence.

PMID- 22382641
TI  - Correlation of serum Anti-Mullerian hormone concentrations on day 3 of the in
      vitro fertilization stimulation cycle with assisted reproduction outcome in
      polycystic ovary syndrome patients.
AB  - PURPOSE: To investigate whether serum Anti- Mullerian hormone (AMH) on day 3
      could predict controlled ovarian stimulation and reproductive outcomes in women
      with polycystic ovary syndrome. METHODS: A total of 164 PCOS patients undergoing
      their first IVF treatment cycle were prospectively included. Serum AMH levels on
      cycle day 3 was measured. The controlled ovarian stimulation and clinical
      outcomes for the study population were divided according to the <25th, 25 to
      75th, or >75th percentile of serum day-3 AMH. RESULTS: Estradiol levels on hCG
      day and the number of retrieved oocytes significantly increased with increasing
      serum AMH levels, while total consumption of gonadotropin dose showed a
      significant decrease (P < 0.05). Fertilization rate and the number of good
      quality embryos were comparable among the low, average and high groups (P >
      0.05). Embryo implantation rates in the high AMH group was significantly inferior
      to those with low and average AMH concentration (27 versus 48.8 and 50%, P <
      0.01). Clinical pregnancy rates was lower in the high AMH group than that of the
      low and average group (45.9 versus 65 and 66.7%, P = 0.09), but this difference
      was only close to statistical significance. In addition, ordinal regression
      analysis indicated that LH level was the only independent predictor of embryo
      implantation rates (P = 0.017). CONCLUSIONS: In PCOS women, AMH levels on day 3
      of the IVF stimulation cycle positively predict ovarian response to
      gonadotrophins. However, the women with high AMH levels had a significantly
      decreased IR, which may be due to remarkably increased LH concentrations.

PMID- 22382642
TI  - LH receptor gene expression in cumulus cells in women entering an ART program.
AB  - PURPOSE: Luteinizing hormone (LH) exerts its actions through its receptor (LHR),
      which is mainly expressed in theca cells and to a lesser extent in oocytes,
      granulosa and cumulus cells. The aim of the present study was the investigation
      of a possible correlation between LHR gene and LHR splice variants expression in
      cumulus cells and ovarian response as well as ART outcome. METHODS: Forty
      patients undergoing ICSI treatment for male factor infertility underwent a long
      luteal GnRH-agonist downregulation protocol with a fixed 5-day rLH pre-treatment
      prior to rFSH stimulation and samples of cumulus cells were collected on the day
      of egg collection. RNA extraction and cDNA preparation was followed by LHR gene
      expression investigation through real-time PCR. Furthermore, cumulus cells were
      investigated for the detection of LHR splice variants using reverse transcription
      PCR. RESULTS: Concerning LHR expression in cumulus cells, a statistically
      significant negative association was observed with the duration of ovarian
      stimulation (odds ratio = 0.23, p = 0.012). Interestingly, 6 over 7 women who
      fell pregnant expressed at least two specific types of LHR splice variants (735
      bp, 621 bp), while only 1 out of 19 women that did not express any splice variant
      achieved a pregnancy. CONCLUSIONS: Consequently, the present study provide a step
      towards a new role of LHR gene expression profiling as a biomarker in the
      prediction of ovarian response at least in terms of duration of stimulation and
      also a tentative role of LHR splice variants expression in the prediction of
      pregnancy success.

PMID- 22382643
TI  - Clinical outcomes of elective single morula embryo transfer versus elective
      single blastocyst embryo transfer in IVF-ET.
AB  - PURPOSE: To compare the clinical outcomes of elective single morula embryo
      transfer (eSMET) versus elective single blastocyst embryo transfer (eSBET) in
      selected patients. METHODS: This study was a retrospective study which analyzed
      for 271 cycles in women under 37 years of age who are undergoing their first or
      second trial of in vitro fertilization-embryo transfer (IVF-ET) from January 2008
      to December 2009. The eSMET was performed on day 4 (n = 130) and the eSBET was
      conducted on day 5 (n = 141). RESULTS: The clinical pregnancy rate (51.5% vs.
      51.8%, p = 0.97), implantation rate (52.3% vs. 52.5%, p = 0.98), and live birth
      rate (39.2% vs. 44.7%, p = 0.36) were similar in the eSMET and eSBET groups,
      respectively. The miscarriage rate of the eSMET group (23.9%) was slightly higher
      than that of the eSBET group (13.7%) (p = 0.12), without reaching statistical
      significance. There was only one case of monozygotic twin pregnancy in each
      group. CONCLUSIONS: The clinical outcomes of day 4 eSMET were comparable to those
      of day 5 eSBET. Therefore, day 4 eSMET is a viable option or an alternative to
      day 5 eSBET, with no difference in success rates.

PMID- 22382644
TI  - Current status of hematopoietic stem cell transplantation for acute radiation
      syndromes.
AB  - Many people believe that hematopoietic stem cell transplantation (HSCT) together
      with various hematopoietic factors may aid or rescue victims of acute radiation
      exposure. However, nearly all patients who have received current HSCT for severe
      bone marrow damage in the past died relatively shortly after transplantation,
      even when engraftment followed by autologous blood cell recovery was observed.
      The causes of death in such cases involved rapidly progressing insults to many
      non-hematopoietic tissues, such as lung and gut, potentially exacerbated by the
      conditioning regimen and immune dysfunction. We should recognize that at present
      avoiding high-dose radiation exposure is the only safe option.

PMID- 22382645
TI  - Colorimetric sensing of trace UO2(2+) by using nanogold-seeded nucleation
      amplification and label-free DNAzyme cleavage reaction.
AB  - In pH 4.4 HAC-NaAC buffer solution at 80  degrees C, nanogold particles (NG)
      strongly enhanced the slow, colored reaction of Ag(i)-gallic acid to form
      nanosilver particles, which exhibited a strong surface plasmon resonance (SPR)
      absorption peak at 460 nm, but the aggregated nanogold particles (ANG) exhibited
      a weak enhancement. The increased absorption value at 460 nm was linear to the NG
      concentration in the range of 3.6-72.5 ng mL(-1) Au. In pH 5.5 MES buffer
      solution at 80  degrees C, single-stranded substrate DNA and DNAzyme hybridize to
      form double-stranded DNA (dsDNA). The presence of uranyl (UO(2)(2+)) resulted in
      cleavage of the substrate DNA of dsDNA, releasing a short, single-stranded DNA
      that can be adsorbed onto the NG and protect them from aggregation; those un
      adsorbed NG were aggregated to ANG. As the UO(2)(2+) concentration increased,
      more short, single-stranded DNA were released, and more NG were protected by the
      cleavage of substrate single-strand DNA, so the colored particle reaction and the
      absorption value at 460 nm enhanced linearly. On those grounds, 0.083-0.67 nmol
      L(-1) UO(2)(2+) can be detected rapidly by this colorimetric sensing assay, with
      a detection limit of 0.04 nmol L(-1).

PMID- 22382646
TI  - Partially saturated fluorinated heterocycles: diastereo- and enantioselective
      synthesis of beta-trifluoromethyl-pyrroline carboxylates.
AB  - The first asymmetric synthesis of beta-trifluoromethylated pyrroline carboxylates
      has been achieved by organocatalytic conjugated addition of adamantyl glycine
      imine to beta-trifluoromethylated enones, followed by a
      deprotection/cyclization/dehydration sequence.

PMID- 22382647
TI  - Cryopreservation of rat islets of Langerhans by vitrification.
AB  - Cryopreservation could be a possible means of addressing the shortage of islets
      of Langerhans. We investigated the effects of EDT324 solution on the
      vitrification of isolated rat islets of Langerhans. Rat pancreatic islets were
      cryopreserved in 10% DMSO by a slow-rate freezing method or were cryopreserved in
      EDT324 solution by vitrification. The cryopreserved islets were compared in terms
      of viability, stimulation index and metabolic function after transplantation.
      After cryopreservation, the viability and stimulation of islets stored in EDT324
      were 92.4% and 6.4, respectively, and were higher than islets stored by slow
      freezing (72.5% and 1.5, respectively). Streptozotocin-induced diabetic rats were
      transplanted with islets cryopreserved in EDT324, which corrected diabetes and
      achieved euglycemia within 2 days after transplantation. These results indicate
      that EDT324 allows successful cryopreservation of rat islets for long-term
      storage as an alternative solution to traditionally used solutions, such as 10%
      DMSO. Transplantation of cryopreserved islets into diabetic rats can achieve
      euglycemia.

PMID- 22382648
TI  - Gender differences in autobiographical narratives: he shoots and scores; she
      evaluates and interprets.
AB  - Research on autobiographical narratives consistently demonstrates that whereas
      women's narratives emphasize evaluative information, men's narratives are
      factually oriented. These narrative differences might reflect gender differences
      in either the autobiographical knowledge base or the way information from the
      knowledge base is selected when a narrative is constructed. The present
      experiment evaluated these two (potentially complementary) hypotheses by
      assessing memory soon after an event and after a period of 6 weeks, using both
      open-ended (narrative) and factually oriented (questionnaire) measures.
      Consistent with past literature, women told longer, richer, more evaluative
      narratives than did men. However, men recalled more factual information both
      initially and after 6 weeks and also constructed narratives that were more
      factually oriented. These data suggest that men and women value factual
      information differently and that these differences influence both the contents of
      the autobiographical knowledge base and the way that information in the knowledge
      base is used to construct personal narratives.

PMID- 22382649
TI  - Don't wait to incubate: immediate versus delayed incubation in divergent
      thinking.
AB  - Previous evidence for the effectiveness of immediate incubation in divergent
      creative tasks has been weak, because earlier studies exhibited a range of
      methodological problems. This issue is theoretically important, as a
      demonstration of the effects of immediate incubation would strengthen the case
      for the involvement of unconscious work in incubation effects. For the present
      experiment, we used a creative divergent-thinking task (alternative uses) in
      which separate experimental groups had incubation periods that were either
      delayed or immediate and that consisted of either spatial or verbal tasks.
      Control groups were tested without incubation periods, and we carried out checks
      for intermittent conscious work on the target task during the incubation periods.
      The results showed significant incubation effects that were stronger for
      immediate than for delayed incubation. Performance was not different between the
      verbal and spatial incubation conditions, and we found no evidence for
      intermittent conscious working during the incubation periods. These results
      support a role for unconscious work in creative divergent thinking, particularly
      in the case of immediate incubation.

PMID- 22382650
TI  - Development of key performance indicators for emergency departments in Ireland
      using an electronic modified-Delphi consensus approach.
AB  - OBJECTIVE: The objective of this study was to develop a consensus among emergency
      medicine (EM) specialists working in Ireland for emergency department (ED) key
      performance indicators (KPIs). METHODS: The method employed was a three-round
      electronic modified-Delphi process. An online questionnaire with 54 potential
      KPIs was set up for round 1 of the Delphi process. The Delphi panel consisted of
      all registered EM specialists in Ireland. Each indicator on the questionnaire was
      rated using a five-point Likert-type rating scale. Agreement was defined as at
      least 70% of the responders rating an indicator as 'agree' or 'strongly agree' on
      the rating scale. Data were analysed using standard descriptive statistics. Data
      were also analysed as the mean of the Likert rating with 95% confidence intervals
      (95% CIs). Sensitivity of the ratings was examined for robustness by
      bootstrapping the original sample. Statistical analyses were carried out using
      SPSS version 16.0. RESULTS: The response rates in rounds 1, 2 and 3 were 86, 88
      and 88%, respectively. Ninety-seven potential indicators reached agreement after
      the three rounds. In the context of the Donabedian structure-process-outcome
      framework of performance indicators, 41 (42%) of the agreed indicators were
      structure indicators, 52 (54%) were process indicators and four (4%) were outcome
      indicators. Overall, the top-three highest rated indicators were: presence of a
      dedicated ED clinical information system (4.7; 95% CI 4.6-4.9), ED compliance
      with minimum design standards (4.7; 95% CI 4.5-4.8) and time from ED arrival to
      first ECG in suspected cardiac chest pain (4.7; 95% CI 4.5-4.9). The top-three
      highest rated indicators specific to clinical care of children in EDs were: time
      to administration of antibiotics in children with suspected bacterial meningitis
      (4.6; 95% CI 4.5-4.8), separate area available within EDs (seeing both adults and
      children) to assess children (4.4; 95% CI 4.2-4.6) and time to administration of
      analgesia in children with forearm fractures (4.4; 95% CI 4.2-4.7). CONCLUSION:
      Employing a Delphi consensus process, it was possible to reach a consensus among
      EM specialists in Ireland on a suite of 97 KPIs for EDs.

PMID- 22382651
TI  - Positional sensitivity as a confounder in diagnosis of severity of obstructive
      sleep apnea.
AB  - PURPOSE: The apnea-hypopnea index (AHI) is used to grade obstructive sleep apnea
      (OSA) into mild, moderate, and severe forms. Obstructive events are most common
      in the supine position. The amount of supine sleep thus influences total AHI. Our
      aim was to determine the prevalence of position-dependent OSA (POSA) and its
      relation to OSA severity classification as recommended by the American Academy of
      Sleep Medicine (AASM). METHODS: Two hundred sixty-five subjects were recruited
      from primary care hypertension clinics. Whole-night respiratory recordings were
      performed to determine the AHI in the supine and non-supine positions,
      respectively. POSA was defined as supine AHI twice the non-supine AHI with supine
      AHI >=5. RESULTS: Fifty-three percent had POSA, 22% had non-position-dependent
      OSA, and 25% had normal respiration. By AASM classification, 81 subjects did not
      have OSA, but 42% of them had some degree of obstruction when supine, and 5
      subjects would have been classified as moderate-severe if they had only slept
      supine. Conversely, of the 53 classified as mild OSA, 30% would have changed to a
      more severe classification if they had exclusively slept supine. CONCLUSIONS:
      POSA was common both in subjects that by AASM classification had OSA as well as
      those without. The severity of OSA, as defined by AASM, could be dependent on
      supine time in a substantial amount of subjects.

PMID- 22382652
TI  - Subjective, anatomical, and functional nasal evaluation of patients with
      obstructive sleep apnea syndrome.
AB  - BACKGROUND: Studies have shown a high occurrence of nasal alterations in patients
      with obstructive sleep apnea syndrome (OSAS), but no studies have used different
      methods to evaluate the nose of patients with OSAS. The objective of this study
      was to evaluate the nose of patients with OSAS, compare them to controls, and
      correlate the different methods used to evaluate the nose. METHODS: Forty-seven
      patients with moderate/severe OSAS and 20 controls who were matched for gender,
      age, and body mass index were included. Questionnaires regarding sleep and nasal
      symptoms, physical examination, rhinoscopy, nasofibroscopy, nasal inspiratory
      peak flow (NIPF), and acoustic rhinometry (AR) measurements were performed.
      RESULTS: In the OSAS group, 33 (70.2%) were male, with a mean age of 53.2 +/- 9.1
      years. In the control group, 13 (65%) were male, with a mean age of 53.7 +/- 9.7
      years. The OSAS group had a higher score on the nasal symptoms scale (p < 0.01)
      and a higher frequency of nasal alterations [presence of septal deviation,
      clinical complaints (p = 0.01) and hypertrophy of the inferior nasal turbinate (p
      < 0.01)]. The NIPF and AR parameters could not differentiate between the OSAS and
      control groups. There were no significant correlations among the different
      methods used to evaluate the nose. Lower NIPF values were capable of predicting
      higher apnea-hypopnea index scores (p = 0.007). CONCLUSION: Clinical complaints
      and nasal alterations as measured by rhinoscopy and nasofibroscopy were
      associated with the presence of OSAS, which was not the case for the NIPF and AR
      parameters. The results of different evaluation methods were not correlated with
      each other.

PMID- 22382653
TI  - Elevated fractalkine in patients with obstructive sleep apnea hypopnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) has been
      increasingly linked to cardiovascular disease. Inflammatory processes associated
      with OSAHS may contribute to atherosclerosis in these patients. Fractalkine is a
      unique chemokine which has both adhesive and chemoattractant functions. We tested
      the hypothesis that OSAHS patients have increased fractalkine. METHODS AND
      RESULTS: We studied 20 patients (18 males and 2 females) with newly diagnosed
      OSAHS, who were free of other diseases, had never been treated for OSAHS, and
      were taking no medications. We compared fractalkine measurements in these
      patients to measurements obtained in 15 control subjects (14 males and 1 female)
      who were matched for age and body mass index, and in whom occult OSAHS was
      excluded. Plasma fractalkine levels were significantly higher in patients with
      OSAHS than in controls (463.15 +/- 110.78 versus 364.67 +/- 64.81 pg/mL, F =
      2.58, P = 0.004). Fractalkine were associated with AHI (r = 0.756, P < 0.0001),
      lowest oxygen saturation (r = -0.466, P = 0.005), and mean oxygen saturation (r =
      -0.344, P = 0.043). Plasma fractalkine levels were significantly decreased in
      patients with OSAHS after four nights nCPAP (463.15 +/- 110.78 versus 416.75 +/-
      97.67 pg/mL, P = 0.001). CONCLUSIONS: OSAHS is associated with elevated levels of
      fractalkine, a marker of inflammation related to atherosclerosis. The severity of
      OSAHS is proportional to the fractalkine level.

PMID- 22382654
TI  - Prolapse repair using the ElevateTM kit: prospective study on 70 patients.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to examine the anatomical
      and functional results of prolapse repair by a vaginal approach using the Elevate
      kit. METHODS: This was a prospective study of 70 patients presenting with
      symptomatic urogenital prolapse. Twenty Elevate Anterior, 16 Posterior, and 34
      Anterior and Posterior repair systems were placed. Perioperative and
      postoperative complications were assessed. The patients were interviewed at 2
      months and 1 year post-surgery. RESULTS: Recurrences were recorded in 21 patients
      (31.3%) at the 1-year follow-up. However, at the 1-year follow-up, there were 14
      cases (20.9%) of direct recurrence (two anterior, two posterior, and ten combined
      anterior and posterior) compared with seven cases (10.4%) of indirect recurrence.
      Of the 21 failures (stage >= 2), 13 were stage 2 with the leading edge above the
      hymen. None of the patients underwent revision surgery. The exposure rate was
      4.5%. The anterior and posterior shrinkage rates were 68.7% and 31.9%,
      respectively. There were four cases of de novo dyspareunia. Patients reported a
      significant decrease in the impact of pelvic floor distress on the PFIQ-7
      questionnaire, but an improvement on the PFDI-20. There was no improvement in
      sexual function (PISQ-12). CONCLUSIONS: The ElevateTM kit is associated with
      satisfactory functional results. However, the anatomical results require ongoing
      evaluation.

PMID- 22382655
TI  - Pelvic floor muscle strength predicts stress urinary incontinence in primiparous
      women after vaginal delivery.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to investigate obstetrical,
      neonatal, and clinical predictors of stress urinary incontinence (SUI) focusing
      on pelvic floor muscle (PFM) strength after vaginal delivery. METHODS: A cross
      sectional study was used, and potential predictors of SUI were collected 5-7
      months postpartum on 192 primiparous women. Predictors that reached significance
      in the bivariate analysis were entered into the Classification and Regression
      Tree that identified interactions among them and cutoff points to orient clinical
      practice. RESULTS: PFM strength was the strongest predictor of SUI. A combination
      of PFM strength <= 35.5 cmH(2)O, prior SUI, newborn weight > 2.988 g, and new
      onset of SUI in pregnancy predicted SUI. The model's accuracy was high (84%; p =
      0.00). CONCLUSIONS: From the four predictors identified, three are modifiable by
      physical therapy. This could be offered to women targeting at PFM strength >35.5
      cmH(2)O at the postpartum as well as at the prevention of SUI before and during
      pregnancy.

PMID- 22382656
TI  - Red ginseng inhibits scratching behavior associated with atopic dermatitis in
      experimental animal models.
AB  - Pruritus is a severe symptom that is difficult to treat in atopic dermatitis
      patients. Red ginseng (RG), a natural medicine, has various biological activities
      such as anti-inflammatory effects. In this study, we examined the efficacy of RG
      extract (RGE) and its mechanism on experimental atopic dermatitis in mice. The
      effects of RGE on vascular permeability and itching were first evaluated.
      Histamine-induced permeability and itching were significantly inhibited by
      embrocation with RGE as well as diphenhydramine, an antihistamine drug. Next, we
      assessed the therapeutic effect of topical RGE in a mouse model of atopic
      dermatitis. Dermatitis was induced by repeated application of 2,4
      dinitrofluorobenzene (DNFB) acetone solution to the mouse ear. The effects of
      tacrolimus (a calcineurin blocker), dexamethasone (a corticosteroid), and RGE on
      dermatitis and associated scratching behavior were compared. Repeated DNFB
      application caused frequent scratching behaviors and ear swelling. Topical
      treatment with tacrolimus, dexamethasone, and RGE for 8 days before the final
      challenge with DNFB significantly inhibited ear swelling. Tacrolimus and RGE
      significantly inhibited scratching behavior, whereas dexamethasone failed to do
      so. DNFB-induced nerve growth factor expression and nerve fiber extension were
      significantly attenuated by tacrolimus and RGE, but not by dexamethasone. RGE may
      have the potential for treatment of atopic dermatitis.

PMID- 22382657
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: novel PET/SPECT imaging probes for diagnosis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease of the brain associated
      with irreversible cognitive decline, memory impairment, and behavioral changes.
      Postmortem brains of AD patients reveal neuropathologic features, in particular
      the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), which
      contain beta-amyloid peptides and highly phosphorylated tau proteins. Currently,
      AD can only be definitively confirmed by postmortem histopathologic examination
      of SPs and NFTs in the brain. Therefore, SPs and NFTs in the brain may be useful
      as biomarkers for the differential diagnosis of AD; the detection of individual
      SPs and NFTs in vivo by positron-emission tomography (PET) or single-photon
      emission computed tomography (SPECT) should improve diagnosis and also accelerate
      discovery of effective therapeutic agents for AD. Many PET/SPECT imaging probes
      for SPs have already been developed. Several of the PET probes have been shown in
      clinical trials to be useful for the imaging of beta-amyloid plaques in living
      brain tissue. More recently, the development of PET/SPECT probes for in vivo
      imaging of NFTs is an active area of study in the field of molecular imaging
      because the appearance of NFT pathology correlates well with clinical severity of
      dementia. We will review current research on the development of PET/SPECT imaging
      probes for in vivo detection of SPs and NFTs and their application to diagnosis
      and therapy of AD.

PMID- 22382658
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: endoplasmic reticulum stress and immunological stress in pathogenesis of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder,
      accompanied by neuronal loss and the formation of senile plaques in the brain.
      Glial cells, such as microglia, have been shown to be activated and induce
      chronic inflammatory responses in AD brain. The endoplasmic reticulum (ER)
      functions to facilitate protein folding. However, ER stress occurs when cells are
      exposed to stress. Mounting evidence suggests that ER stress is involved in the
      pathology of AD. Meanwhile, recent findings suggested crosstalk between ER stress
      and immune function. However, the mechanisms linking the progression of AD with
      ER and immunological stress are still not clear. In the present paper, we review
      and discuss recent results regarding the mechanism of AD pathogenesis, focusing
      on ER stress and immunological stress.

PMID- 22382659
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: tangle formation, amyloid-beta, and microglia in Alzheimer's disease.
AB  - Pathological hallmarks of Alzheimer's disease (AD) include senile plaques,
      neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile
      plaques are composed of amyloid-beta (Abeta) and are surrounded by microglia, a
      primary immune effector cell in the central nervous system. NFTs are formed by
      the intraneuronal accumulation of hyperphosphorylated tau, and progressive
      synaptic and neuronal losses closely correlate with cognitive deficits in AD.
      Studies on responsible genes of familial AD and temporal patterns of pathological
      changes in brains of patients with Down's syndrome (Trisomy 21), who invariably
      develop neuropathology of AD, have suggested that Abeta accumulation is a primary
      event that influences other AD pathologies. Although details of the interaction
      between AD pathologies remain unclear, experimental evidences to discuss this
      issue have been accumulated. In this paper, we review and discuss recent findings
      that link the AD pathologies to each other. Further studies on the interaction
      between pathologies induced in AD brain may contribute to provide deep insight
      into the pathogenesis of AD and to develop novel therapeutic, prophylactic, and
      early diagnostic strategies for AD.

PMID- 22382660
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: preface: pharmacological/underlying interventions for Alzheimer's
      disease.

PMID- 22382661
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: clinical molecular and genetic studies on Alzheimer's disease.
AB  - Recent advances in clinical molecular and genetic studies on Alzheimer's disease
      (AD) are summarized here. Cerebrospinal fluid (CSF) Abeta42 and tau are the most
      sensitive biomarkers for the diagnosis of AD and prediction of its onset
      following mild cognitive impairment (MCI). Based on this progress, new diagnostic
      criteria for AD dementia, MCI due to AD, and preclinical AD were proposed by the
      National Institute of Aging (NIA) and Alzheimer's Association (AA) in April 2011.
      In these new criteria, progress in CSF biomarker and amyloid imaging studies over
      the past 10 years has added to critical information. The marked contributions of
      basic and clinical studies have established clinical evidence supporting these
      markers. Based on this progress, essential curative therapy for AD is urgently
      expected.

PMID- 22382662
TI  - Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's
      disease: possible involvement of HRD1, a novel molecule related to endoplasmic
      reticulum stress, in Alzheimer's disease.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protective
      mechanism against ER stress in which unfolded proteins accumulated in the ER are
      selectively transported to the cytosol for degradation by the ubiquitin
      proteasome system. We cloned the novel ubiquitin ligase HRD1, which is involved
      in ERAD, and showed that HRD1 promoted amyloid precursor protein (APP)
      ubiquitination and degradation, resulting in decreased generation of amyloid beta
      (Abeta). In addition, suppression of HRD1 expression caused APP accumulation and
      promoted Abeta generation associated with ER stress and apoptosis. Interestingly,
      HRD1 levels were significantly decreased in the cerebral cortex of patients with
      Alzheimer's disease (AD), and the brains of these patients experienced ER stress.
      Our recent study revealed that this decrease in HRD1 was due to its
      insolubilization; however, controversy persists about whether the decrease in
      HRD1 protein promotes Abeta generation or whether Abeta neurotoxicity causes the
      decrease in HRD1 protein levels. Here, we review current findings on the
      mechanism of HRD1 protein loss in the AD brain and the involvement of HRD1 in the
      pathogenesis of AD. Furthermore, we propose that HRD1 may be a target for novel
      AD therapeutics.

PMID- 22382664
TI  - The effect of dexmedetomidine on arterial-cardiac baroreflex function assessed by
      spectral and transfer function analysis.
AB  - PURPOSE: The alpha(2)-adrenergic receptor agonist dexmedetomidine reportedly
      weakens heart rate (HR) responses to 'rapid' (during a few seconds) reduction in
      arterial pressure, but does not affect HR responses to 'gradual' (during 60 s)
      reduction in arterial pressure. As the speed of neurotransmission along the
      parasympathetic nerve is relatively rapid, alteration of parasympathetic-mediated
      arterial-cardiac baroreflex function plays a more important role in HR responses
      to 'rapid' changes in arterial pressure. We therefore hypothesized that
      dexmedetomidine attenuates parasympathetic-mediated arterial-cardiac baroreflex
      function. METHODS: Twelve healthy men received placebo, low-dose (loading, 3
      MUg/kg/h for 10 min; maintenance, 0.2 MUg/kg/h for 60 min) (low-DEX), or moderate
      dose (loading, 6 MUg/kg/h for 10 min; maintenance, 0.4 MUg/kg/h for 60 min)
      (moderate-DEX) dexmedetomidine infusions in a randomized, double-blind, crossover
      study. Before and after 70 min of infusion, arterial-cardiac baroreflex function
      was assessed by spectral and transfer function analysis between arterial pressure
      variability and HR variability. RESULTS: The high-frequency power of systolic
      arterial pressure (SAP) variability increased significantly with low-DEX and
      moderate-DEX infusions (significant interaction effects, P = 0.005), whereas the
      high-frequency power of R-wave-R-wave interval (RRI) variability (as an index of
      cardiac parasympathetic activity) did not change significantly at any dose
      infusions. Then, transfer function gain in the high-frequency range (as an index
      of parasympathetic arterial-cardiac baroreflex) decreased significantly with low
      DEX and moderate-DEX infusions (significant interaction effects, P = 0.007).
      CONCLUSIONS: The present results suggest that dexmedetomidine attenuates
      parasympathetic-mediated arterial-cardiac baroreflex function, implying weakened
      HR response to 'rapid' reduction in arterial pressure.

PMID- 22382665
TI  - Flurbiprofen axetil provides a prophylactic benefit against mesenteric traction
      syndrome associated with remifentanil infusion during laparotomy.
AB  - PURPOSE: Mesenteric traction syndrome (MTS) is caused by PGI(2) release during
      abdominal procedures and is often observed during abdominal surgery. We have
      demonstrated that MTS occurs more frequently in cases using remifentanil than in
      those that are not. The aim of this study was to assess the prophylactic benefit
      of flurbiprofen axetil on MTS in patients undergoing abdominal surgery using
      remifentanil. METHODS: Thirty ASA physical status I and II patients were
      enrolled. They were scheduled to undergo abdominal surgery under general
      anesthesia with remifentanil and were randomly assigned to receive flurbiprofen
      axetil (group F) or saline (group C) preoperatively (n = 15 each). MTS was
      defined according to our simplified diagnostic criteria. Arterial blood pressure
      and heart rate were recorded, and the plasma 6-keto-PGF(1alpha) (a stable
      metabolite of PGI(2)) concentration was measured just before skin incision and at
      20 and 60 min after skin incision (T(0), T(20), T(60)) to confirm the diagnosis
      of MTS. RESULTS: Twelve of 15 (80%) patients developed MTS in group C, whereas
      only 1 of 15 (6.7%) patients in group F developed MTS. At T(20), the group C
      patients showed significantly lower arterial blood pressure (P < 0.05) and a
      faster heart rate (P < 0.01) than those in group F. The mean plasma 6-keto
      PGF(1alpha) concentration was significantly elevated in group C at T(20) (P <
      0.01), whereas the plasma 6-keto-PGF(1alpha) level remained low throughout the
      observation period in group F. CONCLUSIONS: We found that preoperative
      administration of flurbiprofen axetil reduced the incidence of MTS during
      abdominal surgery with remifentanil analgesia.

PMID- 22382666
TI  - Reproductive hormones and interleukin-6 in serious leisure male athletes.
AB  - Lifestyles associated with different types and intensities of exercise result in
      improved health including positive changes in chronic low-grade inflammatory
      biomarkers. Alternatively, some forms of exercise adversely affect reproductive
      health of men, including changes in circulating reproductive hormones. To explore
      the associations between exercise intensity and circulating levels of
      reproductive hormones, and inflammatory analytes in serious leisure athletes
      (triathletes and cyclists) and recreational athletes. Male athletes 18-60 years
      old, 16 triathletes, 46 cyclists and 45 recreational athletes, were recruited to
      provide plasma for the measurement of total testosterone, estradiol, follicular
      stimulating hormone, luteinizing hormone (LH), sex hormone-binding globulin
      (SHBG), cortisol, interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) levels,
      and calculation of free androgen index (FAI) and the estradiol:SHBG ratio (ESR).
      Plasma estradiol concentrations were more than two times higher in cyclists than
      in triathletes and recreational athletes (p < 0.01). Testosterone levels were
      also higher in cyclists than recreational athletes (p < 0.01), but not
      significantly different from triathletes. SHBG levels were higher in triathletes
      and cyclists than in recreational athletes (p < 0.01). LH levels were lower in
      cyclists than in recreational athletes (p < 0.05). IL-6 and IL-1beta levels were
      each two times lower in triathletes than in cyclists (p < 0.05) and IL-6 levels
      were lower in cyclists than in recreational athletes (p < 0.01). IL-1beta levels
      were two times lower in triathletes than in cyclists (p < 0.05). Circulating
      estradiol and testosterone levels were elevated in serious leisure male cyclists.
      This effect is discussed in light in the absence of a substantial concomitant
      change in gonadotropin levels and other variables.

PMID- 22382667
TI  - Energetics of running in top-level marathon runners from Kenya.
AB  - On ten top-level Kenyan marathon runners (KA) plus nine European controls (EC,
      equivalent to KA), we measured maximal oxygen consumption (VO2max) and the energy
      cost of running (Cr) on track during training camps at moderate altitude, to
      better understand the KA dominance in the marathon. At each incremental running
      speed, steady-state oxygen consumption (VO2) was measured by telemetric metabolic
      cart, and lactate by electro-enzymatic method. The speed requiring VO2 = VO2max
      provided the maximal aerobic velocity (numax). The energy cost of running was
      calculated by dividing net VO2 by the corresponding speed. The speed at lactate
      threshold (nu(ThetaAN)) was computed from individual La(b) versus speed curves.
      The sustainable VO2max fraction (Fd) at nu(ThetaAN) (F(ThetaAN)) was computed
      dividing nu(ThetaAN) by numax. The Fd for the marathon (Fmar) was determined as
      Fmar = 0.92 F(ThetaAN). Overall, VO2max (64.9 +/- 5.8 vs. 63.9 +/- 3.7 ml kg(-1)
      min(-1)), numax (5.55 +/- 0.30 vs. 5.41 +/- 0.29 m s(-1)) and Cr (3.64 +/- 0.28
      vs. 3.63 +/- 0.31 J kg(-1) m(-1)) resulted the same in KA as in EC. In both
      groups, Cr increased linearly with the square of speed. F(ThetaAN) was 0.896 +/-
      0.054 in KA and 0.909 +/- 0.068 in EC; Fmar was 0.825 +/- 0.050 in KA and 0.836
      +/- 0.062 in EC (NS). Accounting for altitude, running speed predictions from
      present data are close to actual running performances, if F(ThetaAN) instead of
      Fmar is taken as index of Fd. In conclusion, both KA and EC did not have a very
      high VO2max, but had extremely high Fd, and low Cr, equal between them. The
      dominance of KA over EC cannot be explained on energetic grounds.

PMID- 22382668
TI  - Effect of exercise on the diurnal variation in energy substrate use during a high
      fat diet.
AB  - Aerobic exercise increases 24-h fat oxidation following initiation of a high-fat
      diet. The objective of this study is to examine the time course of increased fat
      oxidation under exercise and sedentary conditions. Eighteen healthy subjects
      completed a randomized crossover design (sedentary and exercise visits) staying
      for five consecutive days in a metabolic chamber each visit. On day 1, 30% of
      energy intake was from fat; days 2-5 had 50% of energy as fat. During exercise,
      subjects rode on a stationary cycle at 45% of VO2max for 1 h in the mornings and
      evenings. Respiratory gases and urinary nitrogen were collected to calculate
      macronutrient oxidation and non-protein respiratory exchange ratio (NPRER). This
      data, collected continuously (24-h periods), were subsequently divided into three
      time segments: (1) exercise + recovery (1000-1200 hours, 2100-2200 hours), (2)
      sleep (2300-0645 hours), and (3) wake (all remaining hours). NPRER on exercise
      versus sedentary visits was lower for the sleep segment (0.77 +/- 0.01 01 vs.
      0.81 +/- 0.01, p < 0.001), higher for the exercise + recovery segment (0.88 +/-
      0.01 vs. 0.86 +/- 0.01, p < 0.001), and was not different for the wake segment.
      Fat oxidation was significantly higher for exercise versus sedentary treatments
      during sleep (41 +/- 2 vs. 31 +/- 2 g), wake (62 +/- 3 vs. 51 +/- 3 g), and
      exercise + recovery segments (33 +/- 3 vs.16 +/- 1 g), but so was fat intake by
      design (171 +/- 8 vs. 128 +/- 7 g/d). Although exercise showed greater fat
      oxidation during all segments, dietary fat intake was also higher. Therefore,
      based on NPRER, the time of day during which the exercise treatment increased the
      ratio of fat to carbohydrate oxidation was during sleep.

PMID- 22382669
TI  - The acute effects of aerobic exercise and modified rugby on inflammation and
      glucose homeostasis within Indigenous Australians.
AB  - This study investigated the acute effects of two exercise modes, including cycle
      ergometry and modified rugby on inflammation and glucose regulation within an
      Indigenous Australian population. Ten sedentary, untrained Indigenous male
      participants volunteered to participate and were not clinically diagnosed with
      cardiovascular or metabolic disorders. Following baseline testing and in a
      randomized cross-over design participants completed two exercise protocols (cycle
      ergometry and modified rugby) of 40-min duration separated by 7 days' recovery.
      Fasting venous blood was collected pre, post, 30, 60 and 240 min post exercise
      for analysis of glucose, insulin, cortisol and inflammatory markers of tumour
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-1 receptor agonist
      (ra) and C-reactive protein (CRP). IL-6 and IL-1ra were significantly (P < 0.05)
      increased within the 240 min post-exercise period, without significant
      differences between protocols (P > 0.05). There were no significant changes
      within or between protocols for TNF-alpha, IL-1beta and CRP (P > 0.05). A
      comparison of insulin resistance: homeostasis model (HOMA) between resting and
      240 min post exercise shows a change from a baseline value of 4.44 (3.71) to 1.76
      (1.67) HOMA in cycle ergometry (P < 0.05) and to 1.54 (1.33) HOMA in modified
      rugby (P < 0.05), without differences between sessions (P > 0.05). This study
      identified similar acute inflammatory and glucose regulatory responses between
      cycle ergometry and modified rugby. Prescribing modified rugby as a mode of
      physical activity may provide Indigenous populations with a community-based
      approach to promote increased engagement in physical activity and assist in the
      acute regulation of glucose disposal and inflammatory cytokines.

PMID- 22382670
TI  - Problems of medical supervision and physiological validity encountered with fixed
      rate step tests.

PMID- 22382672
TI  - Analysis of both pulsatile and streamline blood flow patterns during aerobic and
      resistance exercise.
AB  - Blood flow-induced endothelial shear stress (ESS) during aerobic (AX) and
      resistance (RX) exercise can regulate endothelial function. However, non-invasive
      in vivo ESS estimation is normally obtained only according to Poiseuille's laws
      for streamline flow, rather than using Womersley's approximation for pulsatile
      flows. Here, we sought to determine brachial and femoral artery blood flow
      patterns, based on ESS, flow direction, and flow turbulence, using both pulsatile
      and streamline flow approximations during low- and moderate-intensity AX and RX.
      We performed high-resolution ultrasound imaging and Doppler peak blood flow
      velocity (V) measurements of the brachial and femoral arteries in eight young,
      healthy men during rest and two intensities of AX and RX at 40 and 70% of VO2max
      and 1-RM, respectively. Microhematocrit measurement was used to determine blood
      density (rho) and viscosity (MU). ESS was calculated using Poiseuille's law, ESS
      = 2MU * SR (V/artery diameter), and Womersley's approximation, ESS = 2 KMU * SR,
      where K is a function of Womersley's parameter alpha. Turbulence was determined
      using Reynolds number (Re). Re was calculated using Re = V * artery diameter *
      rho/MU and normalized to resting steady-state values (nRe). ESS increases in a
      dose-dependent manner in the femoral and brachial arteries during both AX and RX
      when using either streamline or pulsatile approximations. However, our findings
      indicate that ESS is underestimated when using Poiseuille's law. Secondly,
      turbulence increases in conduit arteries with exercise intensity in a dose
      dependent manner in both retrograde and antegrade flows during both AX and RX.

PMID- 22382673
TI  - Concentration-response analysis of differential gene expression in the zebrafish
      embryotoxicity test following flusilazole exposure.
AB  - The zebrafish embryotoxicity test (ZET) is considered a promising alternative
      model in predictive toxicology. Currently, morphological assessment of the embryo
      is the main readout for this assay. However, implementation of transcriptomics
      may help to detect more subtle effects, which may increase the sensitivity and
      predictability of the test. In this study, we tested a concentration response of
      flusilazole in the ZET. After exposure for 24 h postfertilization, microarray
      analysis revealed a number of processes to be regulated in a concentration
      dependent way. We identified development related processes, retinol metabolism
      and transcription, as well as processes corresponding to the antifungal mechanism
      of action, steroid biosynthesis, and fatty acid metabolism, to be differentially
      regulated. Retinol metabolism and transcription were already significantly
      altered at concentrations that were not inducing morphological effects.
      Differential expression of genes related to steroid biosynthesis and fatty acid
      metabolism showed a concentration response similar to morphological response. An
      increase in concentration was also positively associated with an increase in
      magnitude of expression for individual genes within functional processes. Our
      study shows that transcriptomics analysis in the ZET is a more sensitive readout
      of compound-induced effects than morphological assessment. However, the
      interpretation of differential gene expression in terms of predicting
      morphological effects is not straightforward and requires further study.

PMID- 22382675
TI  - Restoration of anthropometric, biochemical and histopathological alterations by
      Lactobacillus casei supplementation in Giardia intestinalis infected renourished
      BALB/c mice.
AB  - The present study describes the in vivo ameliorating effect of Lactobacillus
      casei supplementation in renourished Giardia intestinalis infected BALB/c mice.
      It was observed that daily administration of probiotic 7 days prior to Giardia
      infection to renourished mice, efficiently reduced the excretion of Giardia cysts
      and trophozoite counts, along with significant increased fecal lactobacilli
      counts compared with Giardia-infected mice. It was also observed that oral
      feeding of probiotic to renourished-Giardia-infected mice abrogated all the
      anthropometric and biochemical anomalies. Histologically, morphological and
      cellular alteration of microvillus membrane integrity revealed that probiotic
      administration further ameliorated the mucosal damage in renourished-probiotic
      Giardia-infected mice compared to severe microvillus atrophy, oedematous,
      vacuolated epithelial cells and ileitis in renourished-Giardia and Giardia
      infected mice. Thus, it is suggested that probiotic used as the functional food
      helps in restoration of anthropometric, biochemical alterations and atrophied gut
      by enhancing the goblet cells and reducing the giardiasis.

PMID- 22382676
TI  - Beta-lactams resistance and presence of class 1 integron in Pseudomonas spp.
      isolated from untreated hospital effluents in Brazil.
AB  - The aim of the present study was to investigate the resistance profile, to detect
      the presence of beta-lactam resistance genes, phenotypic expression of efflux
      pump systems and class 1 integrons in Pseudomonas spp. strains obtained from
      untreated hospital effluents. Effluent samples were collected from four hospitals
      in Porto Alegre, RS, Brazil. Pseudomonas were isolated on MacConkey agar plates
      and the identification was confirmed by 16S rRNA PCR and biochemical tests.
      Susceptibility testing was determined by disk-diffusion method using 11 different
      beta-lactams and MIC assays were performed on isolates resistant to imipenem and
      ceftazidime. The beta-lactamase genes bla (IMP), bla (VIM), bla (SPM-1), bla (OXA
      23-like), bla (OXA-24-like), bla (OXA-51-like) and the intl1 gene from class 1
      integron were analysed by PCR. One hundred and twenty-four isolates were
      recovered and the most common species was Pseudomonas pseudoalcaligenes. The
      resistance found among the isolates was considered high, 62 (50%) isolates were
      multiresistant. No isolate carrying the beta-lactamase genes tested was found
      among the strains. Seven isolates showed reduction of MIC for imipenem and
      ceftazidime in the presence of cyanide m-chlorophenylhydrazone, indicating the
      hyper expression of efflux pumps. From the 124 isolates, 52 (41.9%) were
      identified as carrying the class 1 integron gene, intI1. Untreated hospital
      effluents could be a source of environmental contamination due to discharge of
      antimicrobial resistant bacteria which can carry integron class 1 and act as a
      reservoir of resistance genes and have efflux pump systems.

PMID- 22382677
TI  - Modified thalamocortical model: a step towards more understanding of the
      functional contribution of astrocytes to epilepsy.
AB  - It is evident that the cortex plays a primary role in seizure generation. At the
      same time, various experimental results clearly confirm that thalamic neurons are
      also actively involved in seizure generation and spreading. On the other hand,
      recent neurophysiologic findings suggest that astrocytes regulate dynamically the
      synaptic activity in neuronal networks. Therefore, in the present study, the
      thalamocortical neural population model (TCPM) is modified by embedding into the
      model the functional role of astrocytes in the regulation of synaptic
      transmission. Using the modified TCPM (MTCPM) we examined the hypothesis that one
      of the possible causes of neural hypersynchronization is the dysfunction of
      astrocytes in the regulatory feedback loop. Then, two MTCPMs are coupled via
      excitatory synapses and the astrocytes are also coupled together through gap
      junctions. Utilizing the MTCPM and CMTCPM, the transition from normal to
      malfunctioned states is analyzed using a dynamical system approach. In this way,
      the hypothesis is investigated and it is demonstrated that the healthy astrocytes
      provide feedback control to regulate neural activity. That is, the astrocytes
      compensate to a large extent variations in the coupling between neural
      populations and maintain the balance between the excitation and inhibition
      levels. However, the malfunctioned astrocytes are no longer able to regulate
      and/or compensate the excessive increase of the inter-population coupling
      strength. As a consequence, disruption of the signaling function of astrocytes
      could contribute to the neuronal hyperexcitability and generating epileptiform
      activity. These results suggest that astrocytes might be one of the potential
      targets for the treatment of epilepsy.

PMID- 22382678
TI  - Chol understandings of suicide and human agency.
AB  - According to ethnographic material collected since 2003, the Chol Mayan
      indigenous people in southern Mexico have different causal explanations for
      suicide. It can be attributed to witchcraft that forces victims to take their
      lives against their own will, to excessive drinking, or to fate determined by
      God. However, it can also be conceived of as a conscious decision made by a
      person overwhelmed by daily problems. Drawing from the theoretical framework
      developed by Laura M. Ahearn, inspired by practice theory, the paper contends
      that these different explanations operate within two different logics or
      understandings of human agency. The first logic attributes responsibility to
      supernatural causes such as witchcraft or divine destiny, and reflects Chol
      notions of personhood. The second logic accepts personal responsibility for
      suicide, and is related to processes of social change such as the introduction of
      wage labor, education and a market economy. The contemporary Chol resort to both
      logics to make sense of the human drama of suicide.

PMID- 22382679
TI  - Conformational analysis of therapeutic proteins by hydroxyl radical protein
      footprinting.
AB  - Unlike small molecule drugs, therapeutic protein pharmaceuticals must not only
      have the correct amino acid sequence and modifications, but also the correct
      conformation to ensure safety and efficacy. Here, we describe a method for
      comparison of therapeutic protein conformations by hydroxyl radical protein
      footprinting using liquid chromatography-mass spectrometry (LC-MS) as an
      analytical platform. Hydroxyl radical protein footprinting allows for rapid
      analysis of the conformation of therapeutic proteins based on the apparent rate
      of oxidation of various amino acids by hydroxyl radicals generated in situ.
      Conformations of Neupogen(r), a patented granulocyte colony-stimulating factor
      (GCSF), were compared to several expired samples of recombinant GCSF, as well as
      heat-treated Neupogen(r). Conformations of different samples of the therapeutic
      proteins interferon alpha-2A and erythropoietin were also compared. Differences
      in the hydroxyl radical footprint were measured between Neupogen(r) and the
      expired or mishandled GCSF samples, and confirmed by circular dichroism
      spectroscopy. Samples that had identical circular dichroism spectra were also
      found to be indistinguishable by hydroxyl radical footprinting. The method is
      applicable to a wide variety of therapeutic proteins and formulations through the
      use of separations techniques to clean up the protein samples after radical
      oxidation. The reaction products are stable, allowing for flexibility in sample
      handling, as well as archiving and reanalysis of samples. Initial screening can
      be performed on small amounts of therapeutic protein with minimal training in LC
      MS, but samples with structural differences from the reference can be more
      carefully analyzed by LC-MS/MS to attain higher spatial resolution, which can aid
      in engineering and troubleshooting.

PMID- 22382680
TI  - Nicotinic acetylcholine receptor alpha7 and beta4 subunits contribute nicotine
      induced apoptosis in periodontal ligament stem cells.
AB  - Nicotine, a major component of cigarette smoking, is the important risk factor
      for the development of periodontal disease. However, the mechanisms that underlie
      the cytotoxicity of nicotine in human periodontal ligament stem cells (PDLSCs)
      are largely unknown. Thus, the purpose of this study was to determine the
      cytotoxic effect of nicotine by means of nicotinic acetylcholine receptor (nAChR)
      activation in PDLSCs. We first detected alpha7 and beta4 nAChRs in PDLSCs. The
      gene expressions of alpha7 and beta4 nAChR were increased by nicotine
      administration. Nicotine significantly decreased cell viability at a
      concentration higher than 10(-5) M. DNA fragmentation was also detected at high
      doses of nicotine treatment. Moreover, the detection of sub G1 phase and TUNEL
      assay demonstrated that nicotine significantly induced apoptotic cell death at
      10(-2) M concentration. Western blot analysis confirmed that p53 proteins were
      phosphorylated by nicotine. Under various doses of nicotine, a decrease in the
      anti-apoptotic protein Bcl-2, but an increase in p53 and cleaved caspase-3
      protein levels, was detected in a dose-dependent manner. However, the apoptotic
      effect of nicotine was inhibited by the pretreatment of alpha-bungarotoxin, a
      selective alpha7 nAChR antagonist or mecamylamine, a non-selective nAChR
      antagonist. Finally, increases in the subG1 phase and DNA fragmentation by
      nicotine was attenuated by each nAChR antagonist. Collectively, the presence of
      alpha7 and beta4 nAChRs in PDLSCs supports a key role of nAChRs in the modulation
      of nicotine-induced apoptosis.

PMID- 22382681
TI  - Doxorubicin induces the persistent activation of intracellular transglutaminase 2
      that protects from cell death.
AB  - The activation of transglutaminase 2 (TG2), an enzyme that catalyzes post
      translational modifications of proteins, has been implicated in apoptosis, cell
      adhesion and inflammatory responses. We previously reported that intracellular
      TG2 is activated under oxidative stress conditions, such as ultraviolet
      irradiation, ischemia-reperfusion, and hypoxia. In this study, we examined the
      effect of genotoxic stress on the intracellular activity of TG2 using doxorubicin
      which generates reactive oxygen species that lead to double-strand breakage of
      DNA. We demonstrated that doxorubicin elicits the persistent activation of TG2.
      Doxorubicin-induced TG2 activity was suppressed by treatment with caffeine at the
      early phase, N-acetylcysteine at the mid-phase, and EGTA at the late phase.
      However, treatment with a blocking antibody against TGFbeta or toll-like receptor
      2 showed no effect on TG2 activity, indicating that at least three different
      signaling pathways may be involved in the process of TG2 activation. In addition,
      using MEF cells defective for TG2 and cells overexpressing an activesite mutant
      of TG2, we revealed that doxorubicin-induced cell death is inversely correlated
      with TG2 activity. Our findings indicate that the persistent activation of TG2 by
      doxorubicin contributes to cell survival, suggesting that the mechanism-based
      inhibition of TG2 may be a novel strategy to prevent drug-resistance in
      doxorubicin treatment.

PMID- 22382682
TI  - Rice ASR1 protein with reactive oxygen species scavenging and chaperone-like
      activities enhances acquired tolerance to abiotic stresses in Saccharomyces
      cerevisiae.
AB  - Abscisic acid stress ripening (ASR1) protein is a small hydrophilic, low
      molecular weight, and stress-specific plant protein. The gene coding region of
      ASR1 protein, which is induced under high salinity in rice (Oryza sativa Ilmi),
      was cloned into a yeast expression vector pVTU260 and transformed into yeast
      cells. Heterologous expression of ASR1 protein in transgenic yeast cells improved
      tolerance to abiotic stresses including hydrogen peroxide (H(2)O(2)), high
      salinity (NaCl), heat shock, menadione, copper sulfate, sulfuric acid, lactic
      acid, salicylic acid, and also high concentration of ethanol. In particular, the
      expression of metabolic enzymes (Fba1p, Pgk1p, Eno2p, Tpi1p, and Adh1p),
      antioxidant enzyme (Ahp1p), molecular chaperone (Ssb1p), and pyrimidine
      biosynthesis-related enzyme (Ura1p) was up-regulated in the transgenic yeast
      cells under oxidative stress when compared with wild-type cells. All of these
      enzymes contribute to an alleviated redox state to H2O2-induced oxidative stress.
      In the in vitro assay, the purified ASR1 protein was able to scavenge ROS by
      converting H(2)O(2) to H(2)O. Taken together, these results suggest that the ASR1
      protein could function as an effective ROS scavenger and its expression could
      enhance acquired tolerance of ROS-induced oxidative stress through induction of
      various cell rescue proteins in yeast cells.

PMID- 22382683
TI  - The nuclear receptor PPARs as important regulators of T-cell functions and
      autoimmune diseases.
AB  - Members of the nuclear receptor superfamily function as transcription factors
      involved in innate and adaptive immunity as well as lipid metabolism. These
      highly conserved proteins participate in ligand-dependent or -independent
      regulatory mechanisms that affect gene expression. Peroxisome proliferator
      activated receptors (PPARs), which include PPARalpha, PPARbeta/delta, and
      PPARGamma, are a group of nuclear receptor proteins that play diverse roles in
      cellular differentiation, development, and metabolism. Each PPAR subfamily is
      activated by different endogenous and synthetic ligands. Recent studies using
      specific ligand treatments and cell type-specific PPAR knockout mice have
      revealed important roles for these proteins in T-cell-related autoimmune
      diseases. Moreover, PPARs have been shown to regulate T-cell survival,
      activation, and CD4(+) T helper cell differentiation into the Th1, Th2, Th17, and
      Treg lineages. Here, we review the studies that provide insight into the
      important regulatory roles of PPARs in T-cell activation, survival,
      proliferation, differentiation, and autoimmune disease.

PMID- 22382684
TI  - Targeting RNA-splicing for SMA treatment.
AB  - The central dogma of DNA-RNA-protein was established more than 40 years ago.
      However, important biological processes have been identified since the central
      dogma was developed. For example, methylation is important in the regulation of
      transcription. In contrast, proteins, are more complex due to modifications such
      as phosphorylation, glycosylation, ubiquitination, or cleavage. RNA is the
      mediator between DNA and protein, but it can also be modulated at several levels.
      Among the most profound discoveries of RNA regulation is RNA splicing. It has
      been estimated that 80% of pre-mRNA undergo alternative splicing, which
      exponentially increases biological information flow in cellular processes.
      However, an increased number of regulated steps inevitably accompanies an
      increased number of errors. Abnormal splicing is often found in cells, resulting
      in protein dysfunction that causes disease. Splicing of the survival motor neuron
      (SMN) gene has been extensively studied during the last two decades. Accumulating
      knowledge on SMN splicing has led to speculation and search for spinal muscular
      atrophy (SMA) treatment by stimulating the inclusion of exon 7 into SMN mRNA.
      This mini-review summaries the latest progress on SMN splicing research as a
      potential treatment for SMA disease.

PMID- 22382685
TI  - The transmembrane adaptor protein, linker for activation of T cells (LAT),
      regulates RANKL-induced osteoclast differentiation.
AB  - RANKL induces the formation of osteoclasts, which are responsible for bone
      resorption. Herein we investigate the role of the transmembrane adaptor proteins
      in RANKL-induced osteoclastogenesis. LAT positively regulates osteoclast
      differentiation and is up-regulated by RANKL via c-Fos and NFATc1, whereas LAB
      and LIME act as negative modulators of osteoclastogenesis. In addition, silencing
      of LAT by RNA interference or overexpression of a LAT dominant negative in bone
      marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation.
      Furthermore, LAT is involved in RANKL-induced PLC(gamma) activation and NFATc1
      induction. Thus, our data suggest that LAT acts as a positive regulator of RANKL
      induced osteoclastogenesis.

PMID- 22382686
TI  - Experimental and theoretical investigations on the MMOF selectivity for CO2 vs.
      N2 in flue gas mixtures.
AB  - The adsorption capacity and selectivity of carbon dioxide and nitrogen at 298 K
      have been evaluated for two series of MMOFs built on metal paddle-wheel building
      units, including non-interpenetrated Zn(BDC)(TED)(0.5) (1), Zn(BDC-OH)(TED)(0.5)
      (2), Zn(BDC-NH(2))(TED)(0.5) (3), and interpenetrated Zn(BDC)(BPY)(0.5) (4),
      Zn(BDC)(DMBPY)(0.5) (5), Zn(NDC)(BPY)(0.5) (6) and Zn(NDC)(DMBPY)(0.5) (7)
      framework structures. The ideal adsorbed solution theory (IAST) has been employed
      to predict the adsorption selectivity of CO(2)-N(2) binary mixtures on all seven
      MMOFs using single-component experimental adsorption isotherm data. The
      applicability of IAST to these systems is verified by GCMC simulations performed
      on both single- and multi-component gases.

PMID- 22382687
TI  - The history of the establishment and management philosophies of the Portuguese
      Protected Areas: combining written records and oral history.
AB  - The history of the establishment and management philosophies of the mainland
      Portuguese Protected Areas was reconstructed through the use of written records
      and oral history interviews. The objectives were to review the main philosophies
      in the creation and management of these areas, to assess the influence of
      international PA models, to compare the Portuguese case with other European and
      international literature concerning PAs and to discuss the value of the oral
      history in this research. As main results, it was found that the initial
      management model of "Wilderness (or Yellowstone)" was replaced by the "new
      paradigm" of PAs when the democracy was re-established. Changes in the management
      philosophies within this "new paradigm" were also identified, which resulted in
      the transition of a "Landscape" to a "Nature conservation" model. After the
      establishment of the Natura 2000 network, the "Biodiversity conservation" model
      prevailed. It was also found that the initiative for the establishment of most
      PAs came from the government, although there were few cases of creation due to
      the action of NGOs and municipalities. Finally, oral history interviews enabled
      the addition of information to the literature review, but also provided more
      insight and detail to this history.

PMID- 22382688
TI  - Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an
      integrative modelling study.
AB  - BACKGROUND: Clinical positron emission tomography imaging has demonstrated the
      vast majority of human cancers exhibit significantly increased glucose metabolism
      when compared with adjacent normal tissue, resulting in an acidic tumour
      microenvironment. Recent studies demonstrated reducing this acidity through
      systemic buffers significantly inhibits development and growth of metastases in
      mouse xenografts. METHODS: We apply and extend a previously developed
      mathematical model of blood and tumour buffering to examine the impact of oral
      administration of bicarbonate buffer in mice, and the potential impact in humans.
      We recapitulate the experimentally observed tumour pHe effect of buffer therapy,
      testing a model prediction in vivo in mice. We parameterise the model to humans
      to determine the translational safety and efficacy, and predict patient subgroups
      who could have enhanced treatment response, and the most promising combination or
      alternative buffer therapies. RESULTS: The model predicts a previously unseen
      potentially dangerous elevation in blood pHe resulting from bicarbonate therapy
      in mice, which is confirmed by our in vivo experiments. Simulations predict
      limited efficacy of bicarbonate, especially in humans with more aggressive
      cancers. We predict buffer therapy would be most effectual: in elderly patients
      or individuals with renal impairments; in combination with proton production
      inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors
      (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme
      inhibitors), or with an alternative buffer reagent possessing an optimal pK of
      7.1-7.2. CONCLUSION: Our mathematical model confirms bicarbonate acts as an
      effective agent to raise tumour pHe, but potentially induces metabolic alkalosis
      at the high doses necessary for tumour pHe normalisation. We predict use in
      elderly patients or in combination with proton production inhibitors or buffers
      with a pK of 7.1-7.2 is most promising.

PMID- 22382689
TI  - Repeated transarterial chemoembolisation using different chemotherapeutic drug
      combinations followed by MR-guided laser-induced thermotherapy in patients with
      liver metastases of colorectal carcinoma.
AB  - BACKGROUND: To evaluate a treatment protocol with repeated transarterial
      chemoembolisation (TACE) downsizing before MR-guided laser-induced interstitial
      thermotherapy (LITT) using different chemotherapeutic combinations in patients
      with unresectable colorectal cancer (CRC) liver metastases. METHODS: Two hundred
      and twenty-four patients were included in the current study. Transarterial
      chemoembolisation (mean 3.4 sessions per patient) was performed as a downsizing
      treatment to meet the LITT requirements (number?5, diameter <5 cm). The intra
      arterial protocol consisted of either Irinotecan and Mitomycin (n=77),
      Gemcitabine and Mitomycin (n=49) or Mitomycin alone (n=98) in addition to
      Lipiodol and Embocept in all patients. Post TACE, all patients underwent LITT
      (mean 2.2 sessions per patient). RESULTS: Overall, TACE resulted in a mean
      reduction in diameter of the target lesions of 21.4%. The median time to
      progression was 8 months, calculated from the start of therapy and the median
      local tumour control rate was 7.5 months, calculated as of therapy completion.
      Median survival of patients calculated from the beginning of TACE was 23 months
      (range 4-110 months), in patients treated with Irinotecan and Mitomycin the
      median was 22.5 months, Gemcitabine and Mitomycin 23 months and Mitomycin only 24
      months with a statistically significant difference between the groups (P<0.01).
      CONCLUSION: Repeated TACE offers adequate downsizing of CRC liver metastases to
      allow further treatment with LITT. The combined treatment illustrates substantial
      survival rates and high local tumour control with statistically significant
      differences between the three protocols used. Further randomised trials
      addressing the current study results are required.

PMID- 22382690
TI  - Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells
      treated with melatonin.
AB  - BACKGROUND: Despite recent advances in cancer therapy, the 5-year survival rate
      for Ewing's sarcoma is still very low, and new therapeutic approaches are
      necessary. It was found previously that melatonin induces cell death in the
      Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic
      pathway. METHODS: Melatonin actions were analysed by metabolic viability/survival
      cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot
      for protein activation/expression and electrophoretic mobility shift assay for
      transcription factor activation. RESULTS: Melatonin increases the expression of
      Fas and its ligand Fas L, this increase being responsible for cell death induced
      by the indolamine. Melatonin also produces a transient increase in intracellular
      oxidants and activation of the redox-regulated transcription factor Nuclear
      factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L
      upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell
      lines studied, and do not occur in the other tumour cell lines studied where
      melatonin does not induce cell death. CONCLUSION: Our data offers new insights in
      the study of alternative therapeutic strategies in the treatment of Ewing's
      sarcoma. Further attention deserves to be given to the differences in the
      cellular biology of sensitive tumours that could explain the cytotoxic effect of
      melatonin and the increase in the level of free radicals caused by this molecule,
      in particular cancer types.

PMID- 22382691
TI  - Variation in advanced stage at diagnosis of lung and female breast cancer in an
      English region 2006-2009.
AB  - BACKGROUND: Understanding variation in stage at diagnosis can inform
      interventions to improve the timeliness of diagnosis for patients with different
      cancers and characteristics. METHODS: We analysed population-based data on 17,836
      and 13,286 East of England residents diagnosed with (female) breast and lung
      cancer during 2006-2009, with stage information on 16,460 (92%) and 10,435 (79%)
      patients, respectively. Odds ratios (ORs) of advanced stage at diagnosis adjusted
      for patient and tumour characteristics were derived using logistic regression.
      RESULTS: We present adjusted ORs of diagnosis in stages III/IV compared with
      diagnosis in stages I/II. For breast cancer, the frequency of advanced stage at
      diagnosis increased stepwise among old women (ORs: 1.21, 1.46, 1.68 and 1.78 for
      women aged 70-74, 75-79, 80-84 and >=85, respectively, compared with those aged
      65-69 , P<0.001). In contrast, for lung cancer advanced stage at diagnosis was
      less frequent in old patients (ORs: 0.82, 0.74, 0.73 and 0.66, P<0.001). Advanced
      stage at diagnosis was more frequent in more deprived women with breast cancer
      (OR: 1.23 for most compared with least deprived, P=0.002), and in men with lung
      cancer (OR: 1.14, P=0.011). The observed patterns were robust to sensitivity
      analyses approaches for handling missing stage data under different assumptions.
      CONCLUSION: Interventions to help improve the timeliness of diagnosis of
      different cancers should be targeted at specific age groups.

PMID- 22382692
TI  - Synthesis of allene triazole through iron catalyzed regioselective addition to
      propargyl alcohols.
AB  - Allene triazole derivatives were successfully synthesized for the first time
      through iron catalyzed regioselective triazole addition to tertiary propargyl
      alcohols. The reaction proceeds under mild conditions, giving the desired allene
      triazoles in good to excellent yields (up to 96%). The resulting allene-triazoles
      were confirmed by X-ray crystallography and indicated improved stability.

PMID- 22382693
TI  - The role of procalcitonin in respiratory infections.
AB  - Accurate diagnosis, risk stratification, and decisions about the need for and
      optimal duration of antibiotic therapy are cornerstones of the management of
      patients with respiratory infections. A growing body of evidence supports the use
      of procalcitonin, a marker of bacterial infection, in addition to conventional
      clinical parameters to improve diagnostic and prognostic assessment in patients
      with suspicion of respiratory infections. In addition, several randomized
      controlled trials indicate that procalcitonin may be used for clinical decision
      making about initiation and optimal duration of antibiotic therapy. For patients
      with respiratory infections, procalcitonin-guided antibiotic therapy resulted in
      less antibiotic use without any apparent adverse patient outcome. For other
      infections outcome studies are currently lacking. This review summarizes the
      results of recent investigations of procalcitonin in respiratory infections to
      provide physicians an overview of the utility and limitations of procalcitonin
      when used for bedside decision making.

PMID- 22382694
TI  - Glycosaminoglycans improves early development of zona-free 8-cell rat embryos to
      blastocysts in a chemically defined medium, but not the pregnancy rate following
      transfer of the blastocysts.
AB  - The objective of the present study was to clarify the possible role of the zona
      pellucida (ZP) in early development of rat embryos and to determine the effect of
      glycosaminoglycans on the development of ZP-free 8-cell embryos before or after
      embryo transfer at the blastocyst stage. Eight-cell embryos were divided into
      three groups comprised of, 1) intact controls, 2) embryos with the ZP was removed
      with acidic solution and 3) pairs of ZP-free 8-cell embryos aggregated in a small
      hollow. These embryos were cultured in a chemically defined mR1ECM for 24 h.
      Developmental ability to the blastocyst stage and mean cell number in the
      blastocyst was lower in ZP-free embryos than in intact controls. When these
      blastocysts were transferred, the farrowing rate and efficiency of embryos
      developed to term were also lower in ZP-free embryos, but not in the aggregated
      ones. Supplementation with hyaluronan (HA; 63-250 ug/ml) or heparan sulfate
      proteoglycan (HS; 15 ug/ml) significantly improved blastocyst formation of ZP
      free embryos and the cell number in the blastocyst by reducing the incidence of
      apoptosis. However, there were no beneficial effects of HA or HS on farrowing and
      newborn rates after transfer of the blastocysts. In conclusion, the ZP plays
      roles in maintaining successful development of early rat embryos at least from
      the 8-cell stage not only to the blastocyst stage but also to posttransfer
      stages. Glycosaminoglycans, such as HA or HS, appear to contribute to successful
      cleavage during early development to the blastocyst stage but may be insufficient
      to maintain the posttransfer survival of ZP-free embryos.

PMID- 22382695
TI  - Geometric orientation by humans: angles weigh in.
AB  - Human participants were trained to navigate to two geometrically equivalent
      corners of a parallelogram-shaped virtual environment. The unique shape of the
      environment combined three distinct types of geometric information that could be
      used in combination or in isolation to orient and locate the goals: the angular
      amplitudes of the corners, the relative wall length relationships, and the
      principal axis of symmetry. In testing, participants were placed in manipulated
      versions of the training environment that tested which types of geometry they had
      encoded and how angular information weighed in against the other two geometric
      properties. The test environments were (a) a rectangular environment that removed
      the angular information, (b) a rhombic environment that removed wall length
      information and drastically reduced the principal axis, and (c) a reverse
      parallelogram-shaped environment that placed angular information against both
      wall length and principal axis information. Participants chose accurately in the
      rectangular and rhombus environments, despite the removal of one of the cues. In
      the conflict test, participants preferred corners with the correct angular
      amplitudes over corners that were correct according to both wall length
      relationships and the principal axis. These results are comparable to recent
      findings with pigeons and suggest that angles are a salient orientation cue for
      humans.

PMID- 22382696
TI  - Occurrence of cyclophosphamide and epirubicin in wastewaters by direct injection
      analysis-liquid chromatography-high-resolution mass spectrometry.
AB  - BACKGROUND, AIM, AND SCOPE: According to the high incidence of cancer worldwide,
      the amount of cytostatic drugs administered to patients has increased. These
      compounds are excreted to wastewaters, and therefore become potential water
      contaminants. At this stage, very little is known on the presence and elimination
      of cytostatic compounds in wastewater treatment plants (WWTP). The aim of this
      study was to develop a liquid chromatography-high-resolution mass spectrometry
      (LC-Orbitrap-MS) method for the determination of cyclophosphamide and epirubicin
      in wastewaters. These compounds represent two outmost used cytostatic agents.
      MATERIALS AND METHODS: Extraction and analytical conditions were optimized for
      cyclophosphamide and epirubicin in wastewater. Both solid-phase extraction using
      Oasis 200 mg hydrophilic-lipophilic balanced (HLB) cartridges and direct
      injection analysis were evaluated. Mass spectral characterization and
      fragmentation conditions were optimized at 50,000 resolving power (full width at
      half maximum, m/z 200) to obtain maximum sensitivity and identification
      performance. Quality parameters (recoveries, limits of detection, and
      repetitivity) of the methods developed were determined, and best performance was
      obtained with direct water analysis of the centrifuged wastewater. Finally, this
      method was applied to determine the presence of cyclophosphamide and epirubicin
      in wastewaters from a hospital effluent, an urban effluent, and influents and
      effluents from three WWTP. RESULTS AND DISCUSSION: Cyclophosphamide and
      epirubicin were recovered after 50 mL preconcentration on solid-phase extraction
      200 mg Oasis HLB cartridges (87% and 37%, respectively), and no breakthrough was
      observed by extracting 500 mL of water. Limits of detection were of 0.35 and 2.77
      ng/L for cyclophosphamide and epirubicin, respectively. On the other hand, direct
      injection of water spiked at 1 MUg/L provided recoveries of 107% for
      cyclophosphamide and 44% for epirubicin and limits of detection from 3.1 to 85 ng
      L(-1), respectively. The analysis of wastewaters using direct injection analysis
      revealed the presence of cyclophosphamide and epirubicin in WWTP influents and
      hospital and urban effluents at levels ranging from 5.73 to 24.8 MUg L(-1).
      CONCLUSIONS: The results obtained in this study demonstrate the capability of LC
      Orbitrap-MS for accurate trace analysis of these very polar contaminants. This
      method permitted to identify cyclophosphamide and epirubicin in wastewaters and
      influents of WWTP, but no traces were detected in WWTP effluents. The methodology
      herein developed is sensitive and robust and applicable for screening of a large
      number of samples since no preconcentration is needed.

PMID- 22382697
TI  - Optimization of artificial neural network models through genetic algorithms for
      surface ozone concentration forecasting.
AB  - INTRODUCTION: This study proposes three methodologies to define artificial neural
      network models through genetic algorithms (GAs) to predict the next-day hourly
      average surface ozone (O(3)) concentrations. GAs were applied to define the
      activation function in hidden layer and the number of hidden neurons. METHODS:
      Two of the methodologies define threshold models, which assume that the behaviour
      of the dependent variable (O(3) concentrations) changes when it enters in a
      different regime (two and four regimes were considered in this study). The change
      from one regime to another depends on a specific value (threshold value) of an
      explanatory variable (threshold variable), which is also defined by GAs. The
      predictor variables were the hourly average concentrations of carbon monoxide
      (CO), nitrogen oxide, nitrogen dioxide (NO(2)), and O(3) (recorded in the
      previous day at an urban site with traffic influence) and also meteorological
      data (hourly averages of temperature, solar radiation, relative humidity and wind
      speed). The study was performed for the period from May to August 2004. RESULTS
      AND DISCUSSION: Several models were achieved and only the best model of each
      methodology was analysed. In threshold models, the variables selected by GAs to
      define the O(3) regimes were temperature, CO and NO(2) concentrations, due to
      their importance in O(3) chemistry in an urban atmosphere. CONCLUSION: In the
      prediction of O(3) concentrations, the threshold model that considers two regimes
      was the one that fitted the data most efficiently.

PMID- 22382698
TI  - Heavy metal (Cd, Cr, Cu, Hg, Pb, Zn) concentrations in seven fish species in
      relation to fish size and location along the Yangtze River.
AB  - PURPOSE: The objective of this paper is to assess the regulation of the
      accumulation of heavy metals in the aquatic environment and different fish
      species. METHODS: Water and fish samples were collected from upper to lower
      reaches of the Yangtze River. The heavy metal (Cd, Cr, Cu, Hg, Pb, Zn)
      concentrations in the muscle tissue of seven fishes were measured. Additionally,
      the relationships between heavy metal concentrations in fish tissue and fish size
      (length and weight), condition factor, water layer distribution, and trophic
      level were investigated. RESULTS: Metal concentrations (milligrams per kilogram
      wet weight) were found to be distributed differently among different fish
      species. The highest concentrations of Cu (1.22 mg/kg) and Zn (7.55 mg/kg) were
      measured in Pelteobagrus fulvidraco, the highest concentrations of Cd (0.115
      mg/kg) and Hg (0.0304 mg/kg) were measured in Silurus asotus, and the highest
      concentrations of Pb (0.811 mg/kg) and Cr (0.239 mg/kg) were measured in
      Carassius auratus and Cyprinus carpio. A positive relationship was found between
      fish size and metal level in most cases. The variance of the relationships may be
      the result of differences in habitat, swimming behavior, and metabolic activity.
      In this study, fishes living in the lower water layer and river bottom had higher
      metals concentrations than in upper and middle layers. Benthic carnivorous and
      euryphagous fish had higher metals concentrations than phytoplankton and
      herbivorous fish. Generally, fish caught from the lower reach had higher metals
      concentrations than those from the upper reach. CONCLUSIONS: Cadmium and lead
      concentrations in several fishes exceeded the permissible food consumption
      limits, this should be considered to be an important warning signal.

PMID- 22382699
TI  - Immune mediators of postoperative ileus.
AB  - CLINICAL BACKGROUND: In all patients undergoing abdominal surgery, a transient
      phase of interruption of bowel motility, named postoperative ileus (POI) occurs.
      POI is often accepted as an unavoidable "physiological" response and a self
      limiting complication after surgery although it has a significant impact on
      patient morbidity with prolonged hospitalization and increased costs. Annual
      economic burden has been estimated as much as US $1.47 billion in the USA (Iyer
      et al. in J Manag Care Pharm 15(6):485-494, 2009). PATHOPHYSIOLOGY: The
      pathophysiology has been elucidated within the last decades, demonstrating that
      both, neurogenic and inflammatory mechanisms are involved in response to the
      surgical trauma. It is now generally accepted that POI pathogenesis processes in
      two phases: a first neurogenic phase is accountable for the immediate
      postoperative impairment of bowel motility. This is followed by a second
      immunological phase that can last for days and mainly affects strength and length
      of POI. More recent findings demonstrate a bidirectional interaction between the
      nervous and the immune system, and this interaction significantly contributed to
      our present understanding of POI pathophysiology. Although nerval mechanisms have
      a significant impact in the early phase of POI, the contribution of the immune
      system and subsequently its manipulation has risen as the most promising strategy
      in prevention or treatment of the clinically relevant prolonged form of POI.
      AIMS: The present manuscript will give an update on the inflammatory responses,
      the involved cell types, and participating immune mediators in POI.

PMID- 22382700
TI  - Negative pressure wound therapy for children with an open abdomen.
AB  - PURPOSE: The utility of negative pressure wound therapy (NPWT) in the management
      of adults with an open abdomen has been well documented. We reviewed our
      experience with NPWT in the management of infants and children with this
      condition. METHODS: The records of all children who were treated with NPWT for an
      open abdomen between March 2005 and September 2009 at a single children's
      hospital were reviewed. RESULTS: Twenty-five subjects were identified. They
      included children who developed abdominal compartment syndrome after a laparotomy
      (n = 12) or in whom the abdomen could not be safely closed at the time of
      laparotomy (n = 13). NWPT was accomplished with the vacuum-assisted closure
      (VAC(r)) system in all patients. The median duration for NPWT was 4.5 days. In 16
      subjects, the abdomen was closed successfully after NPWT. In 14 children, the
      abdominal wall fascia was successfully approximated, and two children underwent a
      patch abdominal closure. But nine subjects died before an abdominal closure could
      be attempted. Only two (12.5%) children developed enterocutaneous fistulae.
      CONCLUSIONS: NPWT is a reliable tool for infants and children with an open
      abdomen. Wound management was facilitated and abdominal wall closure was
      ultimately achieved in all survivors. Enterocutaneous fistulae developed in two
      children, however, these were likely due to underlying bowel injury and would
      have occurred despite variations in management of the open abdomen.

PMID- 22382701
TI  - Immune responses triggering colitis and colitis-associated carcinoma.
AB  - Inflammatory bowel diseases compromise of two forms of chronic intestinal
      inflammatory disorders: Crohn's disease and ulcerative colitis. Both forms of
      inflammatory bowel disease result from inappropriate inflammatory responses to
      the intestinal microbiota, but have different underlying immune responses. The
      connection between inflammation and cancer has long been established and
      longstanding inflammatory bowel diseases are an important risk factor for
      developing colorectal cancer. Colitis-associated colorectal cancer pathogenesis
      is highly influenced by specific inflammatory processes during inflammatory bowel
      disease. This article reviews the immunological responses affecting Crohn's
      disease and ulcerative colitis as well as the linkage of inflammatory bowel
      disease to the development of colitis-associated cancer. Finally, we discuss the
      prospects of using new research efforts to devise new immunotherapeutic
      approaches.

PMID- 22382703
TI  - Is simultaneous splenectomy an additive risk factor in surgical treatment for
      active endocarditis?
AB  - PURPOSE: Splenic abscess formation is a serious complication in the setting of
      active endocarditis, and splenectomy is recommended. However, the optimal timing
      for splenectomy is yet undetermined. The purpose of this study was to evaluate
      the role of a one-stage splenectomy and valve surgery for active endocarditis.
      METHODS: Among 202 consecutive endocarditis patients, 18 had splenic lesions on
      preoperative abdominal screening, who underwent cardiac surgery and splenectomy
      as a one-stage procedure (group A) and were compared to patients with
      unremarkable abdominal screening (group B, n = 184) undergoing sole cardiac
      surgery. RESULTS: No difference was observed regarding preoperative
      characteristics (age, gender, New York Heart Association [NYHA] grade, diabetes,
      coronary artery disease, redo surgery, adiposity, smoking), intubation time, and
      prolonged ventilation. There were 23 early postoperative deaths in group B
      (12.5%) vs. none in group A. At 180 days, survival was significantly higher for
      patients in group A (94.4%) vs. group B (67.9%, p = 0.016), although this
      difference did not reach statistical significance (log-rank test, p = 0.073).
      Multivariate Cox proportional hazards regression revealed age above 50 years
      (hazard ratio [HR] 3.327, 95% confidence interval [CI] 1.279-8.650) and NYHA
      class above III (NYHA III or IV: HR 3.117, 95% CI 1.119-8.683, p = 0.030; NYHA
      IV: HR 3.678, 95% CI 1.984-6.817, p < 0.001) as independent risk factors for
      mortality at 180 days. A trend towards a protective factor was observed for
      simultaneous splenectomy (HR = 0.171, 95% CI 0.023-1.255). CONCLUSION:
      Simultaneous valve surgery and splenectomy is an approach for active endocarditis
      complicated by splenic lesions with a low 180-day mortality. Despite the expected
      risk elevation by septic lesions and the additive trauma of a laparotomy,
      patients with simultaneous splenectomy had a favourable outcome regarding early
      mortality and mortality at 6 months.

PMID- 22382702
TI  - The molecular basis of chemoradiosensitivity in rectal cancer: implications for
      personalized therapies.
AB  - INTRODUCTION: Preoperative chemoradiotherapy represents the standard treatment
      for patients with locally advanced rectal cancer. Unfortunately, the response of
      individual tumors to multimodal treatment is not uniform and ranges from complete
      response to complete resistance. This poses a particular problem for patients
      with a priori resistant tumors because they may be exposed to irradiation and
      chemotherapy, treatment regimens that are both expensive and at times toxic,
      without benefit. Accordingly, there is a strong need to establish molecular
      biomarkers that predict the response of an individual patient's tumor to
      multimodal treatment and that indicate treatment-associated toxicities prior to
      therapy. Such biomarkers may guide clinicians in choosing the best possible
      treatment for each individual patient. In addition, these biomarkers could be
      used to identify novel molecular targets and thereby assist in implementing novel
      strategies to sensitize a priori resistant tumors to multimodal treatment
      regimens. OBJECTIVE: The aim of this review is to summarize recent findings about
      the molecular basis of treatment resistance and treatment toxicity in patients
      with rectal cancer. Whole-genome, as well as single-biomarker or multibiomarker,
      analyses and their potential implications will be highlighted. At the end, we
      will outline a future vision of rectal cancer treatment in the era of
      personalized medicine.

PMID- 22382704
TI  - An autopsy study to clarify characteristics of local recurrence after extended
      pancreatectomy with intraoperative radiation therapy in patients with pancreatic
      cancer.
AB  - PURPOSE: Local relapses frequently occur even after curative resection of
      pancreatic cancer. To control local recurrence, we adopted extended radical
      resection combined with intraoperative radiation therapy. METHODS: A
      retrospective review was conducted on 41 patients who underwent extended radical
      pancreatectomy combined with intraoperative radiation therapy for pancreatic
      cancer. Fourteen patients underwent autopsies. We took en bloc specimens of the
      abdominal aorta with surrounding connective tissue to evaluate histological
      characteristics of local status at autopsies. RESULTS: Autopsies disclosed
      microscopic local recurrence in five (36%) of the 14 patients, although no
      evidence of local relapse was observed in either follow-up images or macroscopic
      findings at autopsy. Of the three patients with R1 resection, two had no local
      recurrence microscopically at autopsy. Histological features of local recurrence
      in autopsy samples showed small numbers of cancer cells surrounded by thick
      connective tissue without mass formation. CONCLUSIONS: The autopsy study revealed
      that a characteristic of local recurrence after this treatment was tiny cancer
      cells scattered in dense connective tissue; these cells were undetected by follow
      up imaging.

PMID- 22382705
TI  - Safe management of anastomotic leakage after gastric cancer surgery with enteral
      nutrition via a nasointestinal tube.
AB  - PURPOSE: Anastomotic leakage is a serious complication after gastric cancer
      surgery. Despite the superiority of enteral nutrition (EN), total parenteral
      nutrition (PN) remains the standard therapy for anastomotic leakage. After
      introduction of EN via a nasointestinal tube for patients with anastomotic
      leakage in our institution in 2006, standard nutritional therapy was shifted
      gradually from PN to EN. The present preliminary study evaluates the safety and
      feasibility of EN via a nasointestinal tube for anastomotic leakage after gastric
      cancer surgery. METHODS: Retrospective review of all gastric cancer surgeries
      from 2005 to 2009 (n = 2,588) revealed 53 patients (2.0%) who developed
      anastomotic leakage and were treated conservatively. EN was performed via a
      nasointestinal tube inserted using a guidewire under X-ray fluoroscopy. Clinical
      outcomes and complications following EN were compared with those in patients
      treated with PN (historical control group). The severity of complications was
      evaluated according to the Clavien-Dindo classification. RESULTS: Fifty patients
      were included in the final analysis (three patients died): 29 patients managed by
      EN and 21 managed by PN. There were no significant differences in clinical
      outcomes and the frequency of total complications between the two groups;
      however, there were fewer tube/catheter-related complications in the EN compared
      with the PN group (1 vs. 7, respectively; P < 0.01). There was one epistaxis
      (3.4%; grade I) in the EN group and seven catheter infections (33.3%; grade II)
      in the PN group. The risk of grade II or higher complications was greater in the
      PN than the EN group (11 vs. 4, respectively; P < 0.01), with the greatest
      difference seen in the incidence of catheter infections. On days 7, 10, and 15
      after diagnosis of leakage, the white blood cell count and C-reactive protein
      levels were higher in the PN than in the EN group. The PN group required
      prolonged intravenous antibiotic infusion (P < 0.01). CONCLUSIONS: Nasointestinal
      tube insertion with EN can be performed safely for patients with anastomotic
      leakage. A major advantage of EN is fewer infectious complications. Because EN
      was not inferior to PN in terms of clinical outcome, we recommended that it is
      used in patients with anastomotic leakage after gastric cancer surgery.

PMID- 22382706
TI  - Global survey of controversies in classifying the severity of acute pancreatitis.
AB  - BACKGROUND: The need to accurately classify the severity of patients with acute
      pancreatitis is widely acknowledged but some questions pertinent to this remain
      debatable. The aim of this study was to benchmark opinions of pancreatologists
      worldwide with regard to the issues related to classifying the severity of acute
      pancreatitis. METHODS: An online survey was conducted using an independent
      commercial service. The corresponding authors of all articles pertinent to
      clinical aspects of acute pancreatitis published over the last 5 years were
      invited to participate. RESULTS: A total of 528 invitations were sent and 240
      (45%) responses from 49 countries, representing all the inhabited continents,
      were received. The Atlanta approach to classifying the severity of acute
      pancreatitis was considered adequate for modern clinical practice and clinical
      research by 40 (17%) of the respondents. The determinants-based approach to
      classifying the severity of acute pancreatitis was considered adequate for modern
      clinical practice and clinical research by 188 (78%) and 191 (80%) of the
      respondents, respectively. The definitions of local and systemic determinants of
      severity were also clarified. CONCLUSION: Classifying the severity of acute
      pancreatitis on the basis of Atlanta approach was considered inadequate by the
      overwhelming majority of respondents. An international consensus on the new
      classification of severity of acute pancreatitis has to take into account the
      results of this survey.

PMID- 22382707
TI  - Sex differences in the symptoms and psychological factors that influence quality
      of life in patients with irritable bowel syndrome.
AB  - OBJECTIVE: To investigate the relationship between gender and symptomatology,
      psychological factors, and quality of life (QOL) in irritable bowel syndrome
      (IBS). METHODS: The diagnosis of IBS was made on the basis of the Rome III
      Criteria. A physician obtained demographic and symptom data, Zung Self-Rated
      Anxiety and Depression Scale scores (SAS/SDS), and IBS-specific quality-of-life
      ratings (IBS-QOL). RESULTS: Of the 4015 patients approached, 452 patients were
      diagnosed with IBS. Age ranged from 14 to 79 years (44.05 +/- 14.89 years) and
      the male to female ratio was 1 : 1.3. The gender composition between the four IBS
      subtypes differed significantly (P<0.01). Male and female patients differed in
      their rating of abdominal pain/discomfort in terms of severity and time (P<0.01).
      Groups did not differ with regard to attack frequency. Female patients more
      frequently reported headache, dizziness, backache, muscular soreness,
      inappetence, insomnia, and fatigue (P<0.01). In comparison with men, anxiety and
      depression scores were significantly higher in women (P<0.01). Severity,
      duration, and frequency of abdominal pain/discomfort did not correlate with IBS
      QOL scores. Insomnia/fatigue was negatively correlated with IBS-QOL scores
      (P<0.01). SAS and SDS scores were negatively correlated with IBS-QOL (total score
      and each subscale; P<0.01). CONCLUSION: There are significant gender differences
      in the symptoms, psychological rating, and QOL scores in IBS. Somatic symptoms,
      anxiety, and depression all contribute to the negative impact of IBS. Our
      findings suggest that gender differences should be recognized in IBS treatment.

PMID- 22382709
TI  - On-line solid phase extraction of humic acid from environmental water and
      monitoring with flow-through chemiluminescence.
AB  - An on-line solid phase extraction device combined with flow-through
      chemiluminescence monitoring was presented for the enrichment and determination
      of humic acid (HA) in water samples. The chemiluminescence principle was based on
      the enhancement effect of HA on the Ce(IV)/H(2)SO(4)-rhodamine 6G
      chemiluminescence system. For sample pretreatment, the on-line solid-phase
      extraction (SPE) material was packed into a cartridge which was then installed in
      the manifold. Experimental parameters including reagent concentration, flow rate
      and extraction time, were optimized. Under the optimized conditions, the relative
      standard deviation was 3.6% for determining 2 mg L(-1) HA standard solution and
      the detection limit was 3 MUg L(-1). The proposed method was successfully applied
      to the determination of HA in the range of 0.1-35 mg L(-1). The results were
      validated by spike recovery experiments. The recovery was from 74.0% to 121%,
      which was good enough for the determination of HA in environmental waters.

PMID- 22382708
TI  - Efficacy and safety of entecavir in clinical practice in treatment-naive
      Caucasian chronic hepatitis B patients.
AB  - BACKGROUND: Entecavir is an effective treatment for chronic hepatitis B. However,
      data from clinical practice are limited, especially in hepatitis B e antigen
      (HBeAg)-positive patients. METHODS: We retrospectively analysed data from 190
      nucleos(t)ide-naive chronic hepatitis B patients treated with entecavir (0.5
      mg/day) in 25 Spanish centres. Virological response (hepatitis B virus DNA <50
      IU/ml by PCR), biochemical response (alanine aminotransferase <= 1 * upper limit
      of normal) and serological response were assessed at weeks 12, 24, 36 and 48.
      RESULTS: The cohort was 73% male, 84% Caucasian, and 30% HBeAg-positive. Thirty
      four per cent of the patients who underwent biopsy had advanced
      fibrosis/cirrhosis. At baseline, the median hepatitis B virus DNA was 5.94
      (interquartile range=4.64-7.39) log10 IU/ml. At week 48, 83% of the patients (61%
      HBeAg-positive; 92% HBeAg-negative) achieved a virological response and 82% (78%
      HBeAg-positive; 83% HBeAg-negative) of those with elevated baseline alanine
      aminotransferase showed a biochemical response. Twenty-six per cent (14/54) of
      the HBeAg-positive patients lost HBeAg and 22% (12/54) achieved seroconversion to
      anti-HBe. A significant correlation was observed between virological response at
      week 12 and the rate of seroconversion to anti-HBe at week 48 (P=0.039). This
      correlation was also noted at weeks 24, 36 and 48 (P=0.003, 0.002 and 0.017,
      respectively). Three patients (2%) showed clearance of hepatitis B surface
      antigen. No resistance to entecavir was observed. Treatment with entecavir was
      generally well tolerated. No patients discontinued treatment due to adverse
      events. CONCLUSION: Entecavir monotherapy in clinical practice was well tolerated
      and resulted in a rapid and significant reduction in viral load. A virological
      response at week 12 correlated significantly with the rate of seroconversion to
      anti-HBe at week 48.

PMID- 22382712
TI  - Temperature-dependent development and reproductive traits of Tetranychus
      macfarlanei (Acari: Tetranychidae).
AB  - Development and reproductive traits of Tetranychus macfarlanei Baker & Pritchard
      (Acari: Tetranychidae) were investigated on kidney bean, Phaseolus vulgaris L.,
      at eleven constant temperatures. Tetranychus macfarlanei was able to develop and
      complete its life cycle at temperatures ranging from 17.5 to 37.5 degrees C. At
      15 and 40 degrees C, a few eggs (2-4%) hatched but further development was
      arrested. Development from egg to adult was slowest at 17.5 degrees C and fastest
      at 35 degrees C for both females and males. Using Ikemoto and Takai's linear
      model, the estimated lower developmental thresholds for egg-to-female adult, egg
      to-male adult and egg-to-egg development were 12.9-13.0 degrees C. The thermal
      constants for the respective stages were 110.85, 115.99 and 125.32 degree-days
      (DD). The intrinsic optimum temperatures (T (Phi)) calculated by non-linear SSI
      model were determined as 24.4, 24.4 and 24.2 degrees C for egg-to-female adult,
      egg-to-male adult and egg-to-egg development, respectively. The net reproductive
      rate (R (0)) was highest at 25 degrees C (167.4 females per female) and lowest at
      17.5 degrees C (42.6 females per female). The intrinsic rate of natural increase,
      r (m), increased linearly with the rising of temperature from 0.102 at 17.5
      degrees C to 0.441 day(-1) at 35 degrees C. These values suggested that T.
      macfarlanei could be growing quickly in response to increasing temperatures from
      17.5 to 35 degrees C and provide a basis for predicting its potential
      geographical range.

PMID- 22382713
TI  - Interference in foraging behaviour of European and American house dust mites
      Dermatophagoides pteronyssinus and Dermatophagoides farinae (Acari:
      Pyroglyphidae) by catmint, Nepeta cataria (Lamiaceae).
AB  - The European and American house dust mites, Dermatophagoides pteronyssinus and D.
      farinae, have a huge impact upon human health worldwide due to being the most
      important indoor trigger of atopic diseases such as asthma, rhinitis and atopic
      dermatitis. Preceding studies have shown that the behavioural response of house
      dust mites towards volatile chemicals from food sources can be assessed using a Y
      tube olfactometer assay. In the current study, we used this assay to investigate,
      for the first time, the ability of the essential oil of the catmint plant, Nepeta
      cataria (Lamiaceae), known to repel other ectoparasites affecting human and
      animal health, to interfere with the attraction of D. pteronyssinus and D.
      farinae towards a standard food source (fish flakes). Two distinct chemotypes (A
      and B), enriched in the iridoid compounds (4aS,7S,7aR)-nepetalactone and
      (4aS,7S,7aS)-nepetalactone, and the sesquiterpene (E)-(1R,9S)-caryophyllene, were
      used. Initial assays with a hexane extract of fish flakes (FF extract) confirmed
      attraction of mites to this positive control (P < 0.001 and P < 0.05 for D.
      pteronyssinus and D. farinae respectively), but when presented in combination
      with either N. cataria chemotype, tested across a range of doses (10, 1, 0.1 and
      0.01 MUg), decreasing attraction of mites to their food source was observed as
      the dose augmented. Our study shows that N. cataria, enriched in iridoid
      nepetalactones and (E)-(1R,9S)-caryophyllene, exhibits potent repellent activity
      for house dust mites, and has the potential for deployment in control programmes
      based on interference with normal house dust mite behaviour.

PMID- 22382714
TI  - Taking health needs seriously: against a luck egalitarian approach to justice in
      health.
AB  - In recent works, Shlomi Segall suggests and defends a luck egalitarian approach
      to justice in health. Concurring with G. A. Cohen's mature position he defends
      the idea that people should be compensated for "brute luck", i.e. the outcome of
      actions that it would be unreasonable to expect them to avoid. In his defense of
      the luck egalitarian approach he seeks to rebut the criticism raised by Norman
      Daniels that luck egalitarianism is in some way too narrow and in another too
      wide to uphold justice in health and health care distribution. He points out that
      a pluralistic outline of luck egalitarianism taking into account the moral
      requirement of meeting everyone's basic needs can avoid this line of criticism.
      In this article I argue against the application of such pluralistic luck
      egalitarianism in matters of health distribution. First of all, Segall has not
      shown that luck egalitarianism handles well health distributions above a
      threshold of basic needs. Secondly, his way of avoiding Elizabeth Anderson's
      abandonment objection is theoretically problematic. Finally, I argue that luck
      egalitarianism in general fails to acknowledge the moral foundation of health and
      health care as a basic human entitlement. Thus I conclude that luck
      egalitarianism fails to take health needs seriously and that it cannot therefore
      uphold justice in health.

PMID- 22382717
TI  - Trajectories of body mass and self-concept in black and white girls: the
      lingering effects of stigma.
AB  - As a stigmatizing condition, obesity may lead to the internalization of devalued
      labels and threats to self-concept. Modified labeling theory suggests that the
      effects of stigma may outlive direct manifestations of the discredited
      characteristic itself. This article considers whether obesity's effects on self
      concept linger when obese youth enter the normal body mass range. Using
      longitudinal data from the National Growth and Health Study on 2,206 black and
      white girls, we estimated a parallel-process growth mixture model of body mass
      linked to growth models of body image discrepancy and self-esteem. We found that
      discrepancy was higher and self-esteem lower in formerly obese girls compared to
      girls always in the normal range and comparable to chronically obese girls.
      Neither body image discrepancy nor self-esteem rebounded in white girls despite
      reduction in body mass, suggesting that the effects of stigma linger. Self
      esteem, but not discrepancy, did rebound in black girls.

PMID- 22382718
TI  - Associative stigma among mental health professionals: implications for
      professional and service user well-being.
AB  - In contrast with growing attention given to the stigma experiences of mental
      health service users, the stigma literature has paid almost no attention to
      mental health professionals. This study focuses on experiences of associative
      stigma among these professionals. We investigate the link between associative
      stigma and three dimensions of burnout as well as job satisfaction among mental
      health professionals, and the link of associative stigma with self-stigma and
      client satisfaction among service users. Survey data from 543 professionals and
      707 service users from diverse mental health services are analyzed using
      multilevel techniques. The results reveal that among mental health professionals
      associative stigma is related to more depersonalization, more emotional
      exhaustion, and less job satisfaction. In addition, in units in which
      professionals report more associative stigma, service users experience more self
      stigma and less client satisfaction. The results reveal that associative stigma
      is related to more depersonalization, more emotional exhaustion, and less job
      satisfaction among mental health professionals.

PMID- 22382719
TI  - Mending broken hearts: marriage and survival following cardiac surgery.
AB  - Marriage has long been linked to lower risk for adult mortality in population and
      clinical studies. In a regional sample of patients (n = 569) undergoing cardiac
      surgery, we compared 5-year hazards of mortality for married persons with those
      of widowed, separated or divorced, and never married persons using data from
      medical records and psychosocial interviews. After adjusting for demographics and
      pre- and postsurgical health, unmarried persons had 1.90 times the hazard of
      mortality of married persons; the disaggregated widowed, never married, and
      divorced or separated groups had similar hazards, as did men and women. The
      adjusted hazard for immediate postsurgical mortality was 3.33; the adjusted
      hazard for long-term mortality was 1.71, and this was mediated by married
      persons' lower smoking rates. The findings underscore the role of spouses (both
      male and female) in caregiving during health crises and the social control of
      health behaviors.

PMID- 22382720
TI  - The social context of disablement among older adults: does marital quality matter
      for loneliness?
AB  - Prior research has not adequately considered that disablement occurs within a web
      of relationships that provides socioemotional resources to and/or places demands
      on older adults. Drawing on the stress process and life course perspectives, we
      considered the social context of disablement by examining the influence of
      marital quality on the association between disability and loneliness among
      married older adults. Using data from the National Social Life, Health, and Aging
      Project, we found (1) functional limitations were associated with higher levels
      of loneliness; (2) neither positive nor negative marital quality mediated this
      association, contrary to the stress-deterioration hypothesis; and (3) positive
      (but not negative) marital quality moderated this association, consistent with
      the stress-buffering hypothesis. These associations were similar for women and
      men. Our findings indicate the importance of the social context of disablement,
      as interpersonal resources offer protection from the deleterious socioemotional
      consequences of disability.

PMID- 22382721
TI  - Language proficiency and health status: are bilingual immigrants healthier?
AB  - Bilingual immigrants appear to have a health advantage, and identifying the
      mechanisms responsible for this is of increasing interest to scholars and policy
      makers in the United States. Utilizing the National Latino and Asian American
      Study (NLAAS; n = 3,264), we investigate the associations between English and
      native-language proficiency and usage and self-rated health for Asian and Latino
      U.S. immigrants from China, the Philippines, Vietnam, Mexico, Cuba, and Puerto
      Rico. The findings demonstrate that across immigrant ethnic groups, being
      bilingual is associated with better self-rated physical and mental health
      relative to being proficient in only English or only a native language, and
      moreover, these associations are partially mediated by socioeconomic status and
      family support but not by acculturation, stress and discrimination, or health
      access and behaviors.

PMID- 22382722
TI  - Uridylylation of Herbaspirillum seropedicae GlnB and GlnK proteins is
      differentially affected by ATP, ADP and 2-oxoglutarate in vitro.
AB  - PII are signal-transducing proteins that integrate metabolic signals and transmit
      this information to a large number of proteins. In proteobacteria, PII are
      modified by GlnD (uridylyltransferase/uridylyl-removing enzyme) in response to
      the nitrogen status. The uridylylation/deuridylylation cycle of PII is also
      regulated by carbon and energy signals such as ATP, ADP and 2-oxoglutarate (2
      OG). These molecules bind to PII proteins and alter their tridimensional
      structure/conformation and activity. In this work, we determined the effects of
      ATP, ADP and 2-OG levels on the in vitro uridylylation of Herbaspirillum
      seropedicae PII proteins, GlnB and GlnK. Both proteins were uridylylated by GlnD
      in the presence of ATP or ADP, although the uridylylation levels were higher in
      the presence of ATP and under high 2-OG levels. Under excess of 2-OG, the GlnB
      uridylylation level was higher in the presence of ATP than with ADP, while GlnK
      uridylylation was similar with ATP or ADP. Moreover, in the presence of ADP/ATP
      molar ratios varying from 10/1 to 1/10, GlnB uridylylation level decreased as ADP
      concentration increased, whereas GlnK uridylylation remained constant. The
      results suggest that uridylylation of both GlnB and GlnK responds to 2-OG levels,
      but only GlnB responds effectively to variation on ADP/ATP ratio.

PMID- 22382723
TI  - Stability and gelation behavior of bovine serum albumin pre-aggregates in the
      presence of calcium chloride.
AB  - We study, using wide-angle and small-angle light scattering techniques, the
      stability and aggregation/gelation behaviors of denatured filamentous bovine
      serum albumin pre-aggregates (BSA-PAs), induced by CaCl(2). It is observed that
      transparent filamentous gels can be formed not only at low CaCl(2) concentrations
      but also at high CaCl(2) concentrations, while turbid gels are obtained at
      intermediate CaCl(2) concentrations. Although the filamentous gels at low CaCl(2)
      concentrations and the turbid gels at intermediate CaCl(2) concentrations are
      consistent with the literature observations, the filamentous gels at high CaCl(2)
      concentrations have to be explained by different mechanisms. The latter is
      attributed to the repulsive hydration interactions originating from increased
      surface dipoles generated by counterion binding. Since such surface dipole
      induced hydration is very short-range and occurs mainly on charged or polar
      patches of proteins (thus protected from aggregation), the aggregation of the
      filamentous BSA-PAs at hydrophobic patches at the two ends is still possible,
      leading to formation of the filamentous gels.

PMID- 22382724
TI  - Transarticular fusion for treatment of cystic lesion arising from an odontoid
      fracture.
AB  - INTRODUCTION: Odontoid fractures are the most common upper cervical spine
      fracture. There are two mechanisms in which odontoid fractures occur, most
      commonly hyperflexion of the neck resulting in displacement of the dens
      anteriorly and hyperextension resulting in posterior dens displacement. Type 2
      fractures are the most common and are associated with significant non-union rates
      after treatment. One possible consequence of an odontoid fracture is a synovial
      cyst, resulting in spinal cord compression, presenting as myelopathy or
      radiculopathy. Synovial cysts as a result of spinal fracture, usually of the
      facet joint, are most common in the lumbar region, followed by the thoracic and
      then cervical region; cervical cysts are rare. Fracture and subsequent cyst
      formation is thought to be related to hyper-motion or trauma of the spine. This
      is reinforced by the appearance of spinal synovial cysts most commonly at the
      level of L4/5; this being the region with the biggest weight-bearing function.
      The most common site of cervical cyst formation is at the level of C7/T1; this is
      a transitional joint subjected to unique stress and mechanical forces not present
      at higher levels. Treatment of a cervical synovial cyst at the level of the
      odontoid is challenging with little information available in the literature. The
      majority of cases appear to implement posterior surgical resection of the cyst,
      with fusion of adjacent cervical vertebrae to stabilise the fracture, resulting
      in restricted range of movement. CASE PRESENTATION: We describe a case concerning
      a 39-year-old female who presented with uncertain cause of odontoid fracture,
      resulting in a cystic lesion compressing the upper cervical spinal cord. OUTCOME:
      Minimal invasive surgery of C1/C2 transarticular fusion was successfully
      performed resulting in significant improvement of neurological symptoms in this
      patient. At 1-year follow-up, the cyst had resolved without surgical removal and
      this was confirmed by radiological measures.

PMID- 22382725
TI  - Expert's comment concerning grand rounds case entitled "transarticular fusion for
      treatment of cystic lesion arising from an odontoid fracture" (by Ruth M. Parks,
      Matthias A. Konig, Bronek Boszczyk and Masood Shafafy).

PMID- 22382726
TI  - A geometrical model of vertical translation and alar ligament tension in atlanto
      axial rotation.
AB  - INTRODUCTION: While allowing the greatest range of axial rotation of the entire
      spine with 40 degrees  to each side, gradual restraint at the extremes of motion
      by the alar ligaments is of vital importance. In order for the ligaments to
      facilitate a gradual transition from the neutral to the elastic zone, a complex
      interaction of axial rotation and vertical translation via the biconvex articular
      surfaces is essential. The aim of this investigation is to establish a
      geometrical model of the intricate interaction of the alar ligaments and vertical
      translatory motion of C1/C2 in axial rotation. METHODS: Bilateral alar ligaments
      including the odontoid process and condylar bony entheses were removed from six
      adult cadavers aged 65-89 years within 48 h of death. All specimens were judged
      to be free of abnormalities with the exception of non-specific degenerative
      changes. Dimensions of the odontoid process and alar ligaments were measured.
      Graphical multiplanar reconstruction of atlanto-axial rotation was done in the
      transverse and frontal planes for the neutral position and for rotation to 40
      degrees  with vertical translation of 3 mm. The necessary fibre elongation of the
      alar ligaments in the setting with and without vertical translation of the atlas
      was calculated. RESULTS: The mean diameter of the odontoid process in the
      sagittal plane was 10.6 mm (SD 1.1). The longest fibre length was measured from
      the posterior border of the odontoid enthesis to the posterior border of the
      condylar enthesis with an average of 13.2 mm (SD 2.5) and the shortest between
      the lateral (anterior) border odontoid enthesis and the anterior condylar
      enthesis with an average of 8.2 mm (SD 2.2). In graphical multiplanar
      reconstruction of atlanto-axial rotation to 40 degrees  without vertical
      translation of C1/C2, theoretical alar fibre elongation reaches 27.1% for the
      longest fibres, which is incompatible with the collagenous structure of the alar
      ligaments. Allowing 3 mm caudal translation of C1 on C2 at 40 degrees  rotation,
      as facilitated by the biconvex atlanto-axial joints, reduces alar fibre
      elongation to 23.3%. CONCLUSION: The biconvex configuration of the atlanto-axial
      joints is an integral feature of the functionality of upper cervical spine as it
      allows gradual vertical translation of the atlas against the axis during axial
      rotation, with gradual tensing of the alar ligaments. Vertical translation on its
      own, however, does not explain the tolerance of the alar ligaments towards the
      maximum of 40 degrees  of rotation and is most likely synergistic with the
      effects of the coupled motion of occipitocervical extension during rotation.

PMID- 22382728
TI  - CuN6 Jahn-Teller centers in coordination frameworks comprising fully condensed
      Kuratowski-type secondary building units: phase transitions and magneto
      structural correlations.
AB  - The metal-organic framework [Cu(ta)(2)] (Hta = 1H-1,2,3-triazole), containing
      Jahn-Teller active Cu(II) ions and 1,2,3-triazolate ligands, is prepared under
      solvothermal reaction conditions. The compound shows a reversible phase
      transition from the tetragonal crystal system (alpha-[Cu(ta)(2)]: space group
      I4(1)/amd (no. 141), a = 11.8447(7) A, c = 18.9782(13) A, V = 2662.6(3) A(3)) to
      the cubic crystal system (beta-[Cu(ta)(2)]: space group Fd3m (no. 227), a =
      17.4416(15) A, V = 5305.9(8) A(3)) within the temperature range of 120-160 
      degrees C. Both [Cu(ta)(2)] polymorphs have identical bonding topologies that
      might be described as fully condensed Kuratowski-type pentanuclear secondary
      building units of local T(d) point group symmetry in which four Cu(II) ions
      occupy the vertices of an imaginary tetrahedron. alpha-[Cu(ta)(2)], as opposed to
      the high-temperature beta-phase, shows a strong tetragonal Jahn-Teller distortion
      of CuN(6) coordination octahedra. The compounds are characterized by elemental
      and thermogravimetric analyses, single crystal and powder X-ray diffraction, FTIR
      , UV-vis and fluorescence spectroscopy. Magnetic susceptibility investigations
      reveal two different Cu(II) sites at a ratio of 1 : 2, in agreement with the
      solid state structure of [Cu(ta)(2)]. At low temperatures the formation of
      antiferromagnetically coupled Cu(II) dimers is observed, leading to a spin
      frustration of roughly 1/3 of all magnetically active Cu(II) sites.

PMID- 22382727
TI  - Patients' views on an education booklet following spinal surgery.
AB  - PURPOSE: This study evaluated an evidence-based education booklet developed for
      patients undergoing spinal surgery which was used as a treatment intervention in
      a multi-centre, factorial, randomised controlled trial (FASTER: Function after
      spinal treatment, exercise and rehabilitation) investigating the post-operative
      management of spinal surgery patients. This study sought to determine the
      acceptability and content of the booklet to patients. METHODS: Patients receiving
      the educational booklet before discharge from hospital as part of the FASTER
      study were asked to complete an evaluation, which rated the booklet "Your Back
      Operation" with regard to content, information, usability, etc. using forced and
      open questions. This assessment was conducted at the same time as the initial 6
      week post-operative review performed as part of the larger study. RESULTS:
      Therefore, 97% of the 117 trial participants who returned their 6-week evaluation
      and randomised to receive a booklet returned their questionnaire. The booklet was
      highly rated receiving an overall rating of 7 or more out of 10 from 101/111
      (91%), and high ratings for content, readability and information. The booklet's
      key messages were clear to the majority of patients; however, many patients
      highlighted deficiencies with respect to content particularly in relation to
      wound care and exercise. CONCLUSIONS: Patients valued the booklet and rated its
      content highly. Many suggested that the booklet be developed further and there
      was a clear desire for specific exercises to be included even though there is no
      evidence to support specific exercise prescription.

PMID- 22382729
TI  - Behavioural genetics of childhood disorders.
AB  - After a general introduction into genetic risk factors for child psychiatric
      disorders, four specific child psychiatric disorders with a strong genetic
      component, namely, Autism Spectrum Disorders, Attention Deficit / Hyperactivity
      Disorder, Nocturnal Enuresis, and obesity, are discussed in detail. Recent
      evidence of linkage, candidate gene, and genome-wide association studies are
      presented. This chapter ends with a prospectus on further research needs.

PMID- 22382730
TI  - Physicochemical investigations and stability studies of amorphous gliclazide.
AB  - Gliclazide (GLI), a poorly water-soluble antidiabetic, was transformed into a
      glassy state by melt quench technique in order to improve its physicochemical
      properties. Chemical stability of GLI during formation of glass was assessed by
      monitoring thin-layer chromatography, and an existence of amorphous form was
      confirmed by differential scanning calorimetry and X-ray powder diffractometry.
      The glass transition occurred at 67.5 degrees C. The amorphous material thus
      generated was examined for its in vitro dissolution performance in phosphate
      buffer (pH 6.8). Surprisingly, amorphous GLI did not perform well and was unable
      to improve the dissolution characteristics compared to pure drug over entire
      period of dissolution studies. These unexpected results might be due to the
      formation of a cohesive supercooled liquid state and structural relaxation of
      amorphous form toward the supercooled liquid region which indicated functional
      inability of amorphous GLI from stability point of view. Hence, stabilization of
      amorphous GLI was attempted by elevation of T(g) via formation of solid
      dispersion systems involving comprehensive antiplasticizing as well as surface
      adsorption mechanisms. The binary and ternary amorphous dispersions prepared with
      polyvinylpyrrolidone K30 (as antiplasticizer for elevation of T (g)) and Aerosil
      200(r) and/or Sylysia(r) 350 (as adsorbent) in the ratio of 1:1:1 (w/w) using
      kneading and spray-drying techniques demonstrated significant enhancement in rate
      and extent of dissolution of drug initially. During accelerated stability
      studies, ternary systems showed no significant reduction in drug dissolution
      performance over a period of 3 months indicating excellent stabilization of
      amorphous GLI.

PMID- 22382731
TI  - Peripheral lymphocyte subsets as a prognostic indicator of mortality and
      morbidity in healthy dogs.
AB  - To evaluate the relationship among immune status and increased morbidity and
      mortality, peripheral blood lymphocytes (CD3(+), CD4(+), CD8(+) and CD21(+)
      cells) from 32 healthy dogs over 8 years of age were analyzed. Twenty-five of the
      32 dogs were followed-up for 3 years after the analysis; and 14 dogs were found
      to be diseased, and nine dogs died. There was no notable difference between the
      ages of the dogs that died compared with the ones that survived. The relative
      percentage of CD4(+) and the CD4(+):CD8(+) ratio decreased notably in dogs
      falling ill compared with healthy dogs. The relative percentage of CD3(+)
      lymphocytes showed a notable decrease in dogs that died within 3 years in
      comparison with dogs that survived. In a discriminant analysis of morbidity and
      mortality, most patients were correctly classified as diseased or not and
      surviving or dead, respectively. These results indicate that the immunophenotypes
      of peripheral blood lymphocytes in older dogs offer promise as parameters for
      evaluating mortality and morbidity.

PMID- 22382715
TI  - 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation
      of atrial fibrillation: recommendations for patient selection, procedural
      techniques, patient management and follow-up, definitions, endpoints, and
      research trial design.
AB  - This is a report of the Heart Rhythm Society (HRS) Task Force on Catheter and
      Surgical Ablation of Atrial Fibrillation, developed in partnership with the
      European Heart Rhythm Association (EHRA), a registered branch of the European
      Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), and in
      collaboration with the American College of Cardiology (ACC), American Heart
      Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society
      of Thoracic Surgeons (STS). This is endorsed by the governing bodies of the ACC
      Foundation, the AHA, the ECAS, the EHRA, the STS, the APHRS, and the HRS.

PMID- 22382732
TI  - Diversity of fimbrillin among Porphyromonas gulae clinical isolates from Japanese
      dogs.
AB  - Porphyromonas gulae, a gram-negative black-pigmented anaerobe, is a pathogen for
      periodontitis in dogs. An approximately 41-kDa fimbrial subunit protein (FimA)
      encoded by fimA is regarded as associated with periodontitis. In the present
      study, the fimA genes of 17 P. gulae strains were sequenced, and classified into
      two major types. The generation of phylogenetic trees based on the deduced amino
      acid sequence of FimA of P. gulae strains along with sequences from several
      strains of Porphyromonas gingivalis, a major cause of human periodontitis,
      revealed that the two types of FimA (types A and B) of P. gulae were similar to
      type I FimA and types II and III FimA of P. gingivalis, respectively. A PCR
      system for classification was established based on differences in the nucleotide
      sequences of the fimA genes. Analysis of 115 P. gulae-positive oral swab
      specimens from dogs revealed that 42.6%, 22.6%, and 26.1% of them contained type
      A, type B, and both type A and B fimA genes, respectively. Experiments with a
      mouse abscess model demonstrated that the strains with type B fimA caused
      significantly greater systemic inflammation than those with type A. These results
      suggest that the FimA proteins of P. gulae are diverse with two major types and
      that strains with type B fimA could be more virulent.

PMID- 22382733
TI  - Autologous urothelial cells transplantation onto a prefabricated capsular stent
      for tissue engineered ureteral reconstruction.
AB  - In this study, we have fabricated an artificial ureter by transplantation of in
      vitro-expanded urothelial cells onto an in vivo-prefabricated capsular stent
      using tissue engineering methods. Spiral poly (L-lactic acid) (PLLA) stents were
      transplanted into the subcutaneous of Wistar rats for a period of 1, 2 or 3 weeks
      to induce the formation of connective tissue capsules on their surfaces. The
      capsular PLLA stents were then decellularized and further recellularized with
      bladder epithelial cells to fabricate artificial ureters. The results showed that
      the entrapped cells in all capsules remained continuously proliferation and lined
      up in continuous layers. In addition, the urothelial cells on the capsular stents
      with an embedding period of 2 or 3 weeks showed higher proliferative viability
      compared with the cells on the stents with an embedding time of 1 week (P <
      0.05). The results of the study indicated that the prefabricated capsular stents
      could serve as alternative cell carriers for tissue engineered ureters,
      especially with embedding time from 2 to 3 weeks.

PMID- 22382734
TI  - Novel porous scaffolds of poly(lactic acid) produced by phase-separation using
      room temperature ionic liquid and the assessments of biocompatibility.
AB  - Here we prepared three-dimensional (3D) porous-structured biodegradable polymer
      scaffolds for tissue regeneration using room temperature ionic liquids (RTILs) as
      a novel porogen, and addressed their biological properties, including in vitro
      cell growth and differentiation and in vivo tissue compatibility. RTIL based on 1
      butyl-3-methylimidazolium ([bmim]) bearing hydrophilic anion Cl was introduced
      within the polymer structure to provide a pore network. A mixture of poly(lactic
      acid) (PLA) with RTIL dissolved in an organic solvent formed a bi-continuous
      network during the drying process. Selective dissolution of the RTIL phase was
      facilitated in ethanol, which resulted in a porous network of the polymer phase
      with complete removal of the RTIL. The RTILs-assisted porous scaffolds showed a
      typical open-channeled network with pore sizes over 100 MUm and porosities of
      about 86-94%. For the biocompatibility assessments of the scaffolds, mesenchymal
      stem cells (MSCs) derived from rat bone marrow were seeded onto the PLA scaffold,
      and the cell proliferation and osteoblastic differentiation behaviors were
      examined. Results showed a typical on-going increase in the cell population with
      a level comparable to that observed on the tissue culture plastic control,
      indicating good cell compatibility. When cultured in an osteogenic medium, the
      alkaline phosphatase (ALP) activity of the cells on the PLA scaffolds was
      stimulated to increase with time from 7 to 14 days, in a similar manner to that
      on the control. Moreover, the expression of genes related to osteoblasts,
      including collagen type I, osteocalcin and bone sialoprotein, was stimulated on
      the 3D PLA scaffold during culture for up to 14 days, with levels higher than
      those on the control, suggesting the developed scaffold provided a 3D matrix
      condition for osteogenesis. An in vivo pilot study conducted subcutaneously in
      rat for 4 weeks revealed good tissue compatibility of the scaffold, with the
      ingrowth of cells and formation of collageneous tissue around and deep within the
      pores of the scaffold and no significant inflammatory reaction. Taken together,
      this novel method of using RTILs as a pore generator is considered to be useful
      in the development of biocompatible porous polymer scaffolds for tissue
      regeneration.

PMID- 22382735
TI  - Influence of noble metals alloying additions on the corrosion behaviour of
      titanium in a fluoride-containing environment.
AB  - Titanium alloys exhibit excellent corrosion resistance in most aqueous media due
      to the formation of a stable oxide film, and some of these alloys (particularly
      Ti-6Al-7Nb) have been chosen for surgical and odontological implants for their
      resistance and biocompatibility. Treatment with fluorides (F(-)) is known to be
      the main method for preventing plaque formation and dental caries. Toothpastes,
      mouthwashes, and prophylactic gels can contain from 200 to 20,000 ppm F(-) and
      can affect the corrosion behaviour of titanium alloy devices present in the oral
      cavity. In this work, the electrochemical corrosion behaviour of Ti-1M alloys (M
      = Ag, Au, Pd, Pt) was assessed in artificial saliva of pH = 3.0 containing 910
      ppm F(-) (0.05 M NaF) through open circuit potential, E(OC), and electrochemical
      impedance spectroscopy (EIS) measurements. The corrosion behaviour of the Ti-6Al
      7Nb commercial alloy was also evaluated for comparison. E (OC) measurements show
      an active behaviour for all the titanium alloys in fluoridated acidified saliva
      due to the presence of significant concentrations of HF and HF(2) (-) species
      that dissolve the spontaneous air-formed oxide film giving rise to surface
      activation. However, an increase in stability of the passive oxide layer and
      consequently a decrease in surface activation is observed for the Ti-1M alloys.
      This behaviour is confirmed by EIS measurements. In fact, the Ti-6Al-7Nb alloy
      exhibits lower impedance values as compared with Ti-1M alloys, the highest values
      being measured for the Ti-1Au alloy. The experimental results show that the
      corrosion resistance of the studied Ti-1M alloys is similar to or better than
      that of Ti-6Al-7Nb alloy currently used as biomaterial, suggesting their
      potential for dental applications.

PMID- 22382737
TI  - Visualization of microscale particle focusing in diluted and whole blood using
      particle trajectory analysis.
AB  - Inertial microfluidics has demonstrated the potential to provide a rich range of
      capabilities to manipulate biological fluids and particles to address various
      challenges in biomedical science and clinical medicine. Various microchannel
      geometries have been used to study the inertial focusing behavior of particles
      suspended in simple buffer solutions or in highly diluted blood. One aspect of
      inertial focusing that has not been studied is how particles suspended in whole
      or minimally diluted blood respond to inertial forces in microchannels. The
      utility of imaging techniques (i.e., high-speed bright-field imaging and long
      exposure fluorescence (streak) imaging) primarily used to observe particle
      focusing in microchannels is limited in complex fluids such as whole blood due to
      interference from the large numbers of red blood cells (RBCs). In this study, we
      used particle trajectory analysis (PTA) to observe the inertial focusing behavior
      of polystyrene beads, white blood cells, and PC-3 prostate cancer cells in
      physiological saline and blood. Identification of in-focus (fluorescently
      labeled) particles was achieved at mean particle velocities of up to 1.85 m s(
      1). Quantitative measurements of in-focus particles were used to construct
      intensity maps of particle frequency in the channel cross-section and scatter
      plots of particle centroid coordinates vs. particle diameter. PC-3 cells spiked
      into whole blood (HCT = 45%) demonstrated a novel focusing mode not observed in
      physiological saline or diluted blood. PTA can be used as an experimental frame
      of reference for understanding the physical basis of inertial lift forces in
      whole blood and discover inertial focusing modes that can be used to enable
      particle separation in whole blood.

PMID- 22382738
TI  - The performance of real-time PCR, galactomannan, and fungal culture in the
      diagnosis of invasive aspergillosis in ventilated patients with chronic
      obstructive pulmonary disease (COPD).
AB  - Emerging reports have associated chronic pulmonary obstructive disease (COPD)
      with invasive aspergillosis (IA), particularly in patients treated with
      mechanical ventilation and/or corticosteroids. This is a multicentre study in
      which COPD patients demonstrating a new lung infiltrate while being mechanically
      ventilated were prospectively evaluated for the presence of IA. From the 47
      patients studied, Aspergillus fumigatus was recovered in culture in two patients
      (4.2%). While serum galactomannan (GM) was negative for 94% of patients, GM
      levels in respiratory samples were >0.5, >1.0 and >1.5 for 74.5, 40.5, and 21.3%
      of patients, respectively. PCR was positive for 10 patients in the study but did
      not differentiate Aspergillus colonization from infection. The combination of PCR
      and GM in respiratory samples may be an interesting alternative to diagnose IA in
      COPD patients.

PMID- 22382739
TI  - Hypoglycemia-induced convulsive status epilepticus as the initial presentation of
      primary hepatic carcinoma.
AB  - Hypoglycemia is a well-known complication of insulinoma and other non-islet-cell
      tumors like hepatic tumor. In the emergency unit of neurology department,
      hypoglycemia is an uncommon cause of convulsive status epilepticus. We report a
      rare case with hypoglycemia-induced convulsive status epilepticus as the initial
      presentation of primary hepatic carcinoma. The previously healthy 57-year-old
      male peasant presented with persistent unconsciousness and repeated convulsive
      seizures. He was later found to have hepatoma related hypoglycemia. This case
      highlights the importance of blood sugar test in unexplained status epilepticus
      in the emergency room of neurology department. Intravenous glucose infusion
      rather than anti-epileptic drugs might be safer and more effective in treating
      status epilepticus caused by hepatoma related hypoglycemia.

PMID- 22382741
TI  - Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates
      hyperalgesia and allodynia in chronic constriction injury-induced neuropathic
      pain in rats.
AB  - The role of mitogen-activated protein kinase (MAPK) family has been well defined
      in neuropathic pain. Ras and c-Raf constitute an important part of MAP kinase
      family as Ras/Raf/MEK/ERK2 signaling cascade. The present study was designed to
      investigate the analgesic potential of farnesyl thiosalicylic acid, a novel Ras
      inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in chronic constriction
      induced injury (CCI)-induced peripheral neuropathic pain. Neuropathic pain was
      induced by placing four loose ligatures around the sciatic nerve. The development
      of pain was assessed on 14th day in terms of cold allodynia; mechanical
      hyperalgesia and mechanical allodynia by performing acetone test, pinprick and
      Von Frey tests, respectively. Farnesyl thiosalicylic acid (2.5, 5 and 10 MUg) and
      GW 5074 (1, 2 and 4 MUg) were injected intrathecally on 14th day following nerve
      ligature to assess their analgesic potential in CCI model. Nerve ligature-induced
      CCI produced significant neuropathic pain manifestations in terms of cold and
      mechanical allodynia, and mechanical hyperalgesia. Single intrathecal
      administration of farnesyl thiosalicylic acid (5 and 10 MUg) as well as GW 5074
      (2 and 4 MUg) significantly attenuated CCI-induced hyperalgesia and allodynia.
      The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in CCI model
      suggests that pharmacological inhibition of Ras and c-Raf-1 signaling may be
      potentially useful for managing neuropathic pain.

PMID- 22382742
TI  - Effect of cabergoline on increase of several ER stress-related molecules in 6
      OHDA-lesioned mice.

PMID- 22382743
TI  - A hierarchical architecture S/MWCNT nanomicrosphere with large pores for lithium
      sulfur batteries.
AB  - A hierarchical S/MWCNT nanomicrosphere for lithium/sulfur batteries with a high
      power and energy density as well as an excellent cycle life is introduced. Sulfur
      was uniformly coated on the surface of functional MWCNTs, which serves as a
      carbon matrix, to form a typical nanoscale core-shell structure with a sulfur
      layer of thickness 10-20 nm. Then the nanoscale sulfur intermediate composite was
      ball-milled to form interwoven and porous sphere architecture with large pores
      (around 1 MUm to 5 MUm). Different from most sulfur/carbon materials with
      micropore and mesopore structure, the micrometre scale S/MWCNT nanomicrosphere
      with a large pore structure could also exhibit high sulfur utilization and cycle
      retention. It could maintain a reversible capacity of 1000 mA h g(-1) after 100
      cycles at 0.3 A g(-1) current density. And it even remained 780 mA h g(-1) after
      200 cycles at 0.5 A g(-1) and 650 mA h g(-1) after 200 cycles at 1 A g(-1),
      showing a significant cyclability enhancement. It is believed that under the
      collective effect of hierarchical architecture, as well as the existence of
      carboxyl functional groups, sulfur/carbon materials with large pores could also
      exhibit an excellent electrochemical performance. The synthesis process
      introduced here is simple and broadly applicable, which would not only be
      beneficial to design new materials for lithium sulfur batteries but can also be
      extended to many different electrode materials for lithium ion batteries.

PMID- 22382744
TI  - Parallel factor (PARAFAC) kernel analysis of temperature- and composition
      dependent NMR spectra of poly(lactic acid) nanocomposites.
AB  - The parallel factor (PARAFAC) kernel matrix to analyze a sample system stimulated
      by more than one type of perturbation is described. PARAFAC kernel is a
      quantitative representation of the synchronicity and asynchronicity observed
      within the PARAFAC score matrices generated by carrying out two-dimensional (2D)
      correlation analyses. Thus, kernel matrix representation provides more
      intuitively understandable interpretation to the conventional PARAFAC trilinear
      model. In this study, the utility of PARAFAC kernel is demonstrated by the study
      of poly(lactic acid)-nanocomposite undergoing a structural change depending on
      the temperature as well as the clay content in the sample. Seemingly complicated
      variation of nuclear magnetic resonance (NMR) spectra induced by the change in
      the temperature and clay content are readily analyzed by the multiple
      perturbation 2D correlation spectroscopy and PARAFAC kernel. PARAFAC kernel
      revealed that crystalline and amorphous structures of the PLA substantially
      undergo thermal deformation, and these variations are also influenced by the
      presence of the clay.

PMID- 22382746
TI  - Every cell is sacred.

PMID- 22382747
TI  - Maxillary sinus floor elevation combined with a vertical onlay graft.
AB  - We performed maxillary sinus floor elevation combined with a vertical onlay graft
      for a total of 11 sides of nine patients (1 woman and 8 men) in our Hospital. On
      CT, the preoperative minimum alveolar bone thickness with a mean of 1.8 mm was
      improved to 15.3 mm within a month after this surgery. A total of 20 dental
      implants were placed and there was only one failed implant. With the average
      follow-up of 15.6 months, an average of 3.4 mm of bone absorption was found in
      the site of the maxillary sinus and 1.1 mm in the site of the onlay graft. The
      crown-implant ratio in all cases was within the permissible range. Consequently,
      this bone augmentation surgery was considered to be useful.

PMID- 22382745
TI  - Endothelial mitochondria--less respiration, more integration.
AB  - Lining the inner surface of the circulatory system, the vascular endothelium
      accomplishes a vast variety of specialized functions. Even slight alterations of
      these functions are implicated in the development of certain cardiovascular
      diseases that represent major causes of morbidity and mortality in developed
      countries. Endothelial mitochondria are essential to the functional integrity of
      the endothelial cell as they integrate a wide range of cellular processes
      including Ca2+ handling, redox signaling and apoptosis, all of which are closely
      interrelated. Growing evidence supports the notion that impairment of
      mitochondrial signaling in the endothelium is an early event and a causative
      factor in the development of diseases such as atherosclerosis or diabetic
      complications. In this review, we want to outline the significance of
      mitochondria in both physiology and pathology of the vascular endothelium.

PMID- 22382748
TI  - Use of cone beam computed tomography in implant dentistry: the International
      Congress of Oral Implantologists consensus report.
AB  - PURPOSE: The International Congress of Oral Implantologists has supported the
      development of this consensus report involving the use of Cone Beam Computed
      Tomography (CBCT) in implant dentistry with the intent of providing
      scientifically based guidance to clinicians regarding its use as an adjunct to
      traditional imaging modalities. MATERIALS AND METHODS: The literature regarding
      CBCT and implant dentistry was systematically reviewed. A PubMed search that
      included studies published between January 1, 2000, and July 31, 2011, was
      conducted. Oral presentations, in conjunction with these studies, were given by
      Dr. Erika Benavides, Dr. Scott Ganz, Dr. James Mah, Dr. Myung-Jin Kim, and Dr.
      David Hatcher at a meeting of the International Congress of Oral Implantologists
      in Seoul, Korea, on October 6-8, 2011. RESULTS: The studies published could be
      divided into four main groups: diagnostics, implant planning, surgical guidance,
      and postimplant evaluation. CONCLUSIONS: The literature supports the use of CBCT
      in dental implant treatment planning particularly in regards to linear
      measurements, three-dimensional evaluation of alveolar ridge topography,
      proximity to vital anatomical structures, and fabrication of surgical guides.
      Areas such as CBCT-derived bone density measurements, CBCT-aided surgical
      navigation, and postimplant CBCT artifacts need further research. ICOI
      RECOMMENDATIONS: All CBCT examinations, as all other radiographic examinations,
      must be justified on an individualized needs basis. The benefits to the patient
      for each CBCT scan must outweigh the potential risks. CBCT scans should not be
      taken without initially obtaining thorough medical and dental histories and
      performing a comprehensive clinical examination. CBCT should be considered as an
      imaging alternative in cases where the projected implant receptor or bone
      augmentation site(s) are suspect, and conventional radiography may not be able to
      assess the true regional three-dimensional anatomical presentation. The smallest
      possible field of view should be used, and the entire image volume should be
      interpreted.

PMID- 22382749
TI  - Comparison between graft and no-graft in an immediate placed and immediate
      nonfunctional loaded implant.
AB  - PURPOSE: This study compares success rates and hard and periimplant soft tissue
      responses, between placement and nonplacement of the following five different
      types of grafts: autogenous bone (A); deproteinized bovine bone mineral (H);
      demineralized freeze-dried bone allograft (D); A + H; A + D in horizontal gaps
      between implant surfaces and the buccal bone wall, in immediate placed and
      immediate nonfunctional loaded implants in maxillary arch. MATERIAL AND METHODS:
      Forty-one patients with a mean age of 42.5 years were enrolled in this
      retrospective comparative study. Outcome assessments included clinical and
      radiographic evaluation. RESULTS: Patients were followed up on average for 32
      months with a 100% implant survival rate. No significant difference was found
      between the two groups. CONCLUSION: Results of this study suggest that immediate
      placed and immediate restored single implants are valuable therapeutic options in
      the maxillary arch. The types of grafts placement: A, H, D, A + H, and A + D in
      horizontal gaps have no additional benefit in promoting better clinical outcomes
      given that a thick gingival biotype is present.

PMID- 22382750
TI  - Comparison between bioactive fluoride modified and bioinert anodically oxidized
      implant surfaces in early bone response using rabbit tibia model.
AB  - PURPOSE: The aim of this study was to investigate whether bioactive surfaces were
      more favorable to bone than bioinert surfaces by evaluating bone responses around
      two commercial dental implants. MATERIALS AND METHODS: Bioactive fluoride
      modified implants (Osseospeed) were compared with bioinert oxidized implants
      (TiUnite). Field emission scanning electron microscopy, energy dispersive
      spectroscopy, and confocal laser scanning microscopy analyzed the implant surface
      characteristics. Five New Zealand white rabbits were used to evaluate the bone
      response. Each rabbit received two implants: a fluoride-modified implant in one
      tibia and an oxidized implant in the other. Drilling was performed bicortically,
      and a gap defect was created in the upper cortexonly. Bone-to-implant contact and
      bone area were measured on the histological specimens 2 weeks after implant
      insertion. RESULTS: No significant differences were found in surface roughness (P
      > 0.05). The gap defects were almost filled with new bone within a period of 2
      weeks. The histomorphometry revealed no significant differences in bone-to
      implant contact and bone area (P > 0.05). CONCLUSIONS: Within the limitation of
      this study, the bioactive fluoride-modified surface may show no superiority to
      the bioinert anodized surface in early bone response.

PMID- 22382751
TI  - Allograft for maxillary sinus floor augmentation:  a retrospective study of 90
      cases.
AB  - PURPOSE: The aim of this study is to demonstrate the clinical applicability and
      efficacy of an allograft for maxillary sinus augmentations in patients requiring
      placement of dental implants. PATIENTS AND METHODS: Sixty consecutive patients
      underwent a total of 90 sinus augmentations. Twenty-nine were women and 31 men,
      with a mean age of 54 years. Twenty-six patients received a bilateral procedure
      and 34 unilateral. All cases were treated with the lateral wall technique.
      Allograft consisted of demineralized freeze-dried blocks in 6 cases, particulate
      in 82 cases, and a combination of both in 2 cases. In 30 patients, it was
      combined with platelet-rich plasma. A total of 84 implants were inserted. Bone
      samples of grafted areas were obtained in two patients for histological
      examination. RESULTS: Seventy-three implants were clinically successful at the
      reentry time. Eleven implants in seven patients were removed between 15 days and
      6 months after their placement. Seven of these implants were replaced and
      received prostheses as well, for an overall postloading success rate of 95.2%.
      Follow-up for all patients after final restoration was between 12 and 96 months.
      Specimen's histological evaluation revealed bone formation and evidence of
      inflammatory infiltrate. CONCLUSIONS: Based on the findings of this study, it can
      be suggested that the use of the demineralized freeze-dried bone allograft from
      the Banco de Huesos y Tejidos Fundacion Cosme y Damian for sinus augmentation is
      effective and constitutes a feasible therapeutic alternative for implant
      placement.

PMID- 22382752
TI  - Identification of early response genes to roughness and fluoride modification of
      titanium implants in human osteoblasts.
AB  - PURPOSE: Tissue response after implantation determines the success of the healing
      process. This response is not only dependent on the chemical properties of the
      implant surface but also by the surface topography or its roughness. Although in
      vitro and in vivo studies show improved results with rough- and fluoride-modified
      implants, the mechanisms behind these findings are still unknown. METHODS AND
      MATERIALS: Here, we have used a two-step procedure to identify novel genes
      related to the early response of primary human osteoblasts to roughness and
      fluoride-modified titanium implants. RESULTS: Two hundred seventeen genes
      responding to roughness were identified by microarray analysis and 198 genes
      responding to fluoride, 33 genes were common. Those identified genes related to
      bone and mineralization were further investigated by real-time reverse
      transcriptase polymerase chain reaction. After 1 day of culture, toll-like
      receptor 3, ankylosis-progressive homolog, decorin, osteocalcin, and runt-related
      transcription factor-2 were classified as responsive genes to roughness; Distal
      less homeobox-2 and Tuftelin-1 as responsive genes to fluoride treatment.
      Responsive genes to both treatments were collagen type I, parathyroid hormone
      like hormone, hairy and enhancer of split-1, follistatin, ectonucleotide
      pyrophosphatase/phosphodiesterase-1, and thyroid hormone receptor-alpha.
      CONCLUSION: Our strategy was useful for identifying novel genes that might be
      involved in the early response of osteoblasts to rough and fluoride-modified
      titanium implants.

PMID- 22382753
TI  - Anatase-based implants nanocoating on stem cells derived from adipose tissue.
AB  - PURPOSE: The aim of this study was to investigate the effect of a new anatase
      coating with antibacterial properties (Bactercline anatase coating [BAC]) on
      dental implants in the commitment of stem cells derived from adipose tissue to
      osteoblasts. MATERIALS AND METHODS: Using real-time reverse transcription
      polymerase chain reaction, the quantitative expression of specific genes, such as
      transcriptional factors (runx2 and sp7), bone-related genes (spp1, col1a1,
      col3a1, alpl, and fosl1), and mesenchymal stem cells marker (eng), was examined.
      RESULTS: BAC caused induction of bone-related genes such as sp7, fosl1, alpl, and
      spp1. In contrast, the expression of runx2, col3a1, and col1a1 was decreased in
      stem cells treated with BAC with respect to untreated cells. CONCLUSION: The
      obtained results are relevant to better understand the molecular mechanism of
      bone regeneration and as a model for comparing other materials with similar
      clinical effects.

PMID- 22382754
TI  - Accuracy of linear measurements in cone beam computed tomography with different
      voxel sizes.
AB  - OBJECTIVE: To evaluate the accuracy of linear measurements on dry mandible
      specimens using cone beam computed tomography (CBCT) images acquired with
      different voxel sizes. METHODOLOGY: Eight human dry mandibles were submitted to
      CBCT examination, using the i-CAT (Imaging Sciences, Inc. Hatfield, PA) device
      and four protocols with different voxel sizes. Tomographic slices with a more
      central view of the markers, placed on six sites on each mandible, were selected
      to perform measurements. Values obtained from direct measurements on the dry
      mandible after sectioning them on the preestablished sites were compared with
      measurements from the tomographic images and the measurement error. RESULTS:
      There was no statistical difference between the measurement error of the
      protocols (P = 0.606). The mean value of the difference between the values
      obtained in the images and the dry mandible was smaller than 1 mm for all the
      protocols. CONCLUSION: The accuracy of vertical and horizontal measurements,
      using CBCT (i-CAT) for the four protocols, was shown to be comparable with the
      measurements performed on the dry mandible.

PMID- 22382755
TI  - Implant mandibular rehabilitation postoncologic segmental resection:  a clinical
      report.
AB  - In cases of reconstruction of a discontinuity defect of the mandible, the surgeon
      has a major responsibility to maximize function as well as cosmetics and to
      preserve quality of life, restoring mastication, speech, and appearance.
      Treatment of mandibular discontinuity defects is a complex process and, among
      other methods, includes the use of free vascularized flaps. A variety of donor
      sites have been used for this purpose, including the iliac crest, radius,
      scapula, and fibula.At this time, the iliac crest free flap represents a
      versatile reconstruction method after mandibular ablation. This article reports a
      clinical case using the iliac crest free flap for comprehensive reconstruction of
      discontinuity defects in the mandible after resections of an aggressive
      odontogenic tumor. The immediate implant positioning reduced the number of
      surgical procedures and the rehabilitation time.

PMID- 22382756
TI  - A residual granuloma in association with a dental implant.
AB  - At times, dental implants are placed into sites with a history of periapical
      pathology. Sometimes the infection is active, and other times the tooth may have
      been extracted years before implant placement. In either case, the possibility
      exists for long-term residual cysts or infections that can negatively impact the
      prognosis of the implant. In this case report, an implant is placed into a healed
      mandibular ridge several months after extraction of the tooth. A radiolucency was
      noted on routine radiographic examination 2 years later. Surgical inspection and
      histology revealed a periapical granuloma with acute and chronic inflammatory
      cells. After surgical curettage of the site, the patient healed without
      complication. Implants may develop apical pathology as a result of a preexisting
      long-term residual infection.

PMID- 22382757
TI  - The CHRNA5/A3/B4 gene cluster and tobacco, alcohol, cannabis, inhalants and other
      substance use initiation: replication and new findings using mixture analyses.
AB  - Multiple studies have provided evidence for genetic associations between single
      nucleotide polymorphisms (SNPs) located on the CHRNA5/A3/B4 gene cluster and
      various phenotypes related to Nicotine Dependence (Greenbaum et al. 2009). Only a
      few studies have investigated other substances of abuse. The current study has
      two aims, (1) to extend previous findings by focusing on associations between the
      CHRNA5/A3/B4 gene cluster and age of initiation of several different substances,
      and (2) to investigate heterogeneity in age of initiation across the different
      substances. All analyses were conducted with a subset of the Add Health study
      with available genetic data. The first aim was met by modeling onset of tobacco,
      alcohol, cannabis, inhalants, and other substance use using survival mixture
      analysis (SMA). Ten SNPs in CHRNA5/A3/B4 were used to predict phenotypic
      differences in the risk of onset, and differences between users and non-users.
      The survival models aim at investigating differences in the risk of initiation
      across the 5-18 age range for each phenotype separately. Significant or
      marginally significant genetic effects were found for all phenotypes. The genetic
      effects were mainly related to the risk of initiation and to a lesser extent to
      discriminating between users and non-users. To address the second goal, the
      survival analyses were complemented by a latent class analysis that modeled all
      phenotypes jointly. One of the ten SNPs was found to predict differences between
      the early and late onset classes. Taken together, our study provides evidence for
      a general role of the CHRNA5/A3/B4 gene cluster in substance use initiation that
      is not limited to nicotine and alcohol.

PMID- 22382758
TI  - Oral triptans in the preventive management of cluster headache.
AB  - Cluster headache is a rare primary neurovascular headache and a severe pain
      condition with unilateral headache over 15-180 minutes and concomitant unilateral
      autonomic symptoms. The detailed pathophysiology of the condition is still
      unclear. Only a few evidence-based therapeutic options for acute therapy and the
      preventive management of the disease are available. Triptans, in particular
      sumatriptan 6 mg subcutaneously, are highly effective for acute treatment. This
      review focuses on the potential use of oral triptans in the prophylaxis of
      cluster headache.

PMID- 22382761
TI  - pH-dependent assembly of two inorganic-organic hybrid compounds based on
      octamolybdates: an unusual intercalated layer and a 3D 4-connected framework.
AB  - Two novel inorganic-organic hybrid compounds based on octamolybdates, namely,
      [Cu(H(2)L)(2)(gamma-Mo(8)O(26))].(Mo(6)O(19)).2H(2)O (1) and [Cu(H(2)L)(gamma
      Mo(8)O(26))(H(2)O)(2)].5H(2)O (2), where L = 1,1'-(1,5-pentanediyl)bis[2-(4
      pyridyl)benzimidazole], have been successfully synthesized at different pH values
      under hydrothermal conditions. Compound 1, which is hydrothermally prepared at pH
      ~ 3.5, exhibits an entirely new type of intercalated layer. The nanosized
      hexamolybdate anions as guests are introduced into the layers. When the pH value
      is adjusted to 2, a structurally-different complex 2 was obtained. Compound 2
      shows a unique 3D 4-connected framework constructed by inorganic layers and
      H(2)L(2+) ligands as bridges. The two compounds were characterized by elemental
      analyses, IR spectra and TGA. In addition, the electrochemical properties of 1
      modified carbon paste electrode (CPE) have also been investigated in 1 M
      H(2)SO(4) aqueous solution.

PMID- 22382759
TI  - Sinus venous stenosis-associated idiopathic intracranial hypertension without
      papilledema as a powerful risk factor for progression and refractoriness of
      headache.
AB  - Data from two recent studies strongly support the hypothesis that idiopathic
      intracranial hypertension without papilledema (IIHWOP) could represent a powerful
      risk factor for the progression of pain in primary headache individuals. The
      first study highlights that an asymptomatic IIHWOP is much more prevalent than
      believed in the general population and occurs only in central venous stenosis
      carriers. In the second study, about one half of a large consecutive series of
      unresponsive primary chronic headache patients shows significant sinus venous
      stenosis. A continuous or intermittent IIHWOP was detectable in 91% of this
      subgroup and in no patient with normal venography. Moreover, after the lumbar
      puncture, a 2- to 4-week improvement in headache frequency was observed in most
      of the intracranial hypertensive patients. These findings strongly suggest that
      patients prone to primary headache who carry central venous outflow abnormalities
      are at high risk of developing a comorbid IIHWOP, which in turn is responsible
      for the progression and the unresponsiveness of the pain. Based on the available
      literature data, we propose that central sinus stenosis-related IIHWOP, although
      highly prevalent among otherwise healthy people, represents an important
      modifiable risk factor for the progression and refractoriness of pain in patients
      predisposed to primary headache. The mechanism could refer to up to one half of
      the primary chronic headache patients with minimal response to treatments
      referring to specialized headache clinics. Due to the clinical and taxonomic
      relevance of this hypothesis further studies are urgently needed.

PMID- 22382760
TI  - Accumulated hippocampal formaldehyde induces age-dependent memory decline.
AB  - Aging is an important factor in memory decline in aged animals and humans and in
      Alzheimer's disease and is associated with the impairment of hippocampal long
      term potentiation (LTP) and down-regulation of NR1/NR2B expression. Gaseous
      formaldehyde exposure is known to induce animal memory loss and human cognitive
      decline; however, it is unclear whether the concentrations of endogenous
      formaldehyde are elevated in the hippocampus and how excess formaldehyde affects
      LTP and memory formation during the aging process. In the present study, we
      report that hippocampal formaldehyde accumulated in memory-deteriorating diseases
      such as age-related dementia. Spatial memory performance was gradually impaired
      in normal Sprague-Dawley rats by persistent intraperitoneal injection with
      formaldehyde. Furthermore, excess formaldehyde treatment suppressed the
      hippocampal LTP formation by blocking N-methyl-D-aspartate (NMDA) receptor.
      Chronic excess formaldehyde treatment over a period of 30 days markedly decreased
      the viability of the hippocampus and down-regulated the expression of the NR1 and
      NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous
      formaldehyde is a critical factor in memory loss in age-related memory
      deteriorating diseases.

PMID- 22382763
TI  - Prospective electromyographic evaluation of functional postthyroidectomy voice
      and swallowing symptoms.
AB  - BACKGROUND: Voice and swallowing symptoms following thyroidectomy in the absence
      of any demonstration of laryngeal nerves injury are usually considered a
      functional outcome of uncomplicated operations, mainly related to scar formation
      and emotional reaction. They could be related to unapparent laryngeal nerve or
      cricothyroid (CT) muscle injuries detectable only by laryngeal electromyography
      (LEMG). We correlated such symptoms with LEMG patterns. METHODS: A total of 33
      consenting patients undergoing total thyroidectomy (TT) were enrolled. Video
      strobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation
      time (MPT) were performed preoperatively and 3 months postoperatively. Subjective
      evaluation of voice (Voice Impairment Score, or VIS) and swallowing (Swallowing
      Impairment Score, or SIS) were obtained preoperatively and 1 and 3 months
      postoperatively. At 1 month postoperatively LEMG was performed examining
      thyroarytenoid (TA) and CT muscles to evaluate the inferior laryngeal nerve (ILN)
      and the external branch of the superior laryngeal nerve (EBSLN), respectively.
      RESULTS: One patient experienced transient vocal cord palsy and was excluded. The
      remaining 32 patients completed the postoperative evaluation. No significant
      difference was found between preoperative and postoperative AVA and MPT
      parameters. Mean VIS was significantly worse than preoperatively 1 and 3 months
      after TT. No significant difference was found between preoperative and
      postoperative SIS. LEMG evaluation of TA muscle showed decreased voluntary
      activity and spontaneous fibrillation potentials in one patient. LEMG of the CT
      muscle did not reveal any sign of EBSLN injury. CONCLUSIONS: Patients frequently
      complain of subjective symptoms early after TT. LEMG demonstrated the absence of
      subclinical laryngeal nerve injury in all but one patient, confirming their
      functional nature.

PMID- 22382764
TI  - Case-based learning for patient safety: the Lessons Learnt program for UK junior
      doctors.

PMID- 22382765
TI  - Treatment of necrotizing pancreatitis: redefining the role of surgery.
AB  - BACKGROUND: Early surgical intervention in necrotizing pancreatitis (NP) is
      associated with high mortality. Guidelines recommend fine needle aspiration (FNA)
      in patients with NP and signs of sepsis. Because infection of necrosis is
      considered an indication for surgery, operations are often performed early. We
      changed treatment toward a conservative approach with FNA in selected cases only,
      thereby reducing the rate of necrosectomy. METHODS: Retrospectively analyzed
      patients, all operated on for FNA-proven infection of pancreatic necrosis (n =
      20, group 1) were compared to patients subjected to conservative treatment (n =
      24, group 2) who were followed prospectively. RESULTS: Prognostic scores did not
      differ between the two groups, indicating comparable severity: the Acute
      Physiology and Chronic Health Evaluation (APACHE II) score was 19.8 +/- 1.7
      versus 16 +/- 2.2; the Sequential Organ Failure Assessment (SOFA) score was 8.7
      +/- 1.4 versus 6.9 +/- 1.0, the C-reactive protein (CRP) level on day 3 was 243
      +/- 21 versus 291 +/- 21, and the CTSI (CT severity index) was 7.8 +/- 0.5 versus
      7.9 +/- 0.4 (p = ns). Ten patients in group 2 underwent operation because of
      severe extrapancreatic complications. Mortality differed significantly (45% in
      group 1 vs. 8.3% in group 2; p = 0.01). CONCLUSIONS: A highly conservative
      approach avoiding open necrosectomy in NP results in significantly lower
      mortality than previous serial FNA and consecutive indication for surgery in case
      of proven infection. Open surgery in NP should be reserved for concomitant intra
      abdominal complications.

PMID- 22382766
TI  - Retroperitoneal adrenal-sparing surgery for the treatment of Cushing's syndrome
      caused by adrenocortical adenoma: 8-year experience with 87 patients.
AB  - BACKGROUND: The objective of this study was to present our 8-year experience with
      partial adrenalectomy via the retroperitoneal approach for the treatment of
      Cushing's adenoma. METHODS: A total of 93 patients who underwent adrenal surgery
      for Cushing's adenoma from March 2003 to December 2010 were enrolled in this
      study. Preoperative, intraoperative, and postoperative variables were reviewed
      from the database. Student's t test was used to analyze the continuous data, and
      the chi(2) test was used to analyze the categoric data. A value of p < 0.05 was
      considered statistically significant. RESULTS: Adrenal-sparing surgery was
      performed in 87 cases (31 by open surgery, 56 by retroperitoneal laparoscopy).
      Six patients underwent open/laparoscopic total adrenalectomy because of recurrent
      disease or a large size. The cure rate in our series was 97.8%. Hypertension
      resolved in 34 of 64 patients (53.1%), diabetes in 7 of 27 patients (25.9%) and
      obesity in 28 of 48 patients (58.3%). One patient died during the postoperative
      period. The intraoperative complication rate for the open surgery group was
      significantly higher than that for the retroperitoneal laparoscopy group (9.1 vs.
      1.7%). CONCLUSIONS: The retroperitoneal approach is reliable and safe for
      treating Cushing's syndrome. The laparoscopic technique can decrease the
      prevalence of intraoperative complications. Retroperitoneal laparoscopic partial
      adrenalectomy can be performed with extremely low morbidity and achieves an
      excellent outcome, although death may occur during the postoperative period in
      high-risk patients. Postoperative management plays an important role in the
      surgical treatment of Cushing's syndrome.

PMID- 22382767
TI  - Management of esophageal foreign bodies: experience in a developing country.
AB  - BACKGROUND: The outcome of esophagoscopy for removal of suspected esophageal
      foreign bodies (EFBs) is dependent on the FB characteristics and the surgeon's
      experience. This study was conducted to review our experience and highlight
      challenges in the management of EFBs in a developing country. The value of
      radiologic signs in FB detection was also evaluated. METHODS: We conducted a
      retrospective chart review of 131 patients: 58.8% males and 41.9% females aged 8
      months to 64 years, treated for suspected EFBs in our institution over a 13-year
      period. Statistics were derived by univariate analysis RESULTS: Foreign bodies
      were found and retrieved in 118 cases. Coins were the predominant FB in children
      (35%), and bones (25%) and dentures (17%) were predominant in adults. Plain
      radiography was highly useful in detecting FBs in children (coins/metals 100%)
      but less so in adults (bones 25%, dentures 11%). Repeated esophagoscopy attempts
      were encountered more in patients with impacted sharp objects (85%) and were
      recorded significantly among trainee surgeons (p = 0.004). Open esophagotomy was
      carried out in 13 (10%) difficult cases. Major complications including two
      iatrogenic esophageal perforations and one death occurred following esophagoscopy
      by trainee surgeons. CONCLUSIONS: Rigid esophagoscopy is relatively safe and
      useful procedure in trained hands for removal of EFBs. Management of long
      standing EFBs, dentures, and other sharp objects requires the skills of the most
      experienced members of the surgical team for a successful outcome. Open surgical
      treatment is unavoidable in cases of irretrievable esophageal FBs or in the
      presence of esophageal perforation.

PMID- 22382768
TI  - Prognostic significance of the metastatic lymph node ratio in patients with
      gastric cancer.
AB  - BACKGROUND: In gastric cancer, the classification of lymph node status is still a
      controversial prognostic factor. Recent studies have proposed a new prognostic
      factor (metastatic lymph node ratio: MLR) for gastric cancer patients who undergo
      curative resection. The present study tested the hypothesis that MLR was better
      than the current pN staging system by analyzing the correlation between MLR and
      the International Union Against Cancer/American Joint Committee on Cancer
      (UICC/AJCC) staging system, by analyzing the correlation between MLR and 5-year
      overall survival (OS), by comparing area under the curve (AUC), and by performing
      univariate and multivariate analyses for OS. METHODS: Of 409 patients who were
      diagnosed with gastric adenocarcinoma between January 2003 and December 2006, 370
      patients underwent curative resection and were included in this study. The
      prognostic significance of the number of metastatic lymph nodes and the
      metastatic lymph node ratio were compared in AUC and univariate and multivariate
      Cox regression analyses. RESULTS: MLR was significantly correlated with the depth
      of invasion and the number of lymph node metastases (p < 0.001). Increasing MLR
      also was statistically correlated with a lower 5-year OS rate (p < 0.001). The
      AUC of MLR and the number of lymph node metastases were not significantly
      different (p = 0.825). MLR was an independent prognostic factor on multivariate
      analysis, but the number of metastatic lymph nodes was not. CONCLUSIONS: MLR can
      be a prognostic factor in patients who undergo radical resection for gastric
      cancer and can overcome the limitations of existing prognostic factors.

PMID- 22382769
TI  - Options in breast cancer local therapy: who gets what?
AB  - Today, women with primary breast cancer may consider three surgical options:
      breast-conserving surgery (BCS), mastectomy (MT), and mastectomy with
      contralateral prophylactic mastectomy (MT + CPM). In each case, the ipsilateral
      axilla is generally managed with a sentinel node biopsy and possibly an axillary
      lymph node dissection. BCS generally requires breast radiotherapy, except in
      older women having tumors with a favorable prognosis who will receive endocrine
      therapy. In contrast, women treated with MT generally do not require
      radiotherapy, except for those with large tumors or metastases to the axillary
      nodes. Moreover, MT and MT + CPM are usually undertaken with breast
      reconstruction. Yet, most patients today are suitable candidates for BCS, with a
      few relative contraindications. Thus, early pregnancy, previous radiotherapy to
      the breasts, active collagen vascular disease, multicentric breast cancer, large
      tumors (although neoadjuvant systemic therapy can often reduce tumor size), and
      the presence of the BRCA mutation are all relative contraindications to BCS. BRCA
      mutation carriers should consider MT + CPM because their risk of contralateral
      breast cancer is greatly increased. In the U.S., the use of MT for the treatment
      of primary breast cancer has declined in recent years, while MT + CPM rates have
      increased, and BCS rates have remained relatively stable. The underlying reasons
      for these trends are not fully understood. Local therapy options should be
      discussed with each patient in considerable detail, and more studies are needed
      to better elucidate which factors influence a woman's choice of local therapy
      following a breast cancer diagnosis.

PMID- 22382770
TI  - Traumatic aortic injuries associated with major visceral vascular injuries in
      major blunt trauma patients.
AB  - BACKGROUND: The objectives of this study were to report the clinical and
      radiological characteristics and outcomes of a series of acute traumatic aortic
      injuries (ATAIs) with associated injury to major aortic abdominal visceral
      branches (MAAVBs). METHODS: From January 2000 to August 2011, 10 consecutive
      major blunt trauma patients with associated ATAI and injury to MAAVBs (group A)
      and 42 major blunt trauma patients presenting only an ATAI without MAAVB injuries
      (group B) were admitted to our institution. RESULTS: Overall in-hospital
      mortality was 32.7%. In-hospital mortality in group A was 40% and in group B it
      was 31% (p = 0.86). Observed in-hospital mortality was slightly lower than the
      expected in-hospital mortality in both groups. Mean peak creatine phosphokinase
      was significantly higher in group A than in group B patients (23,008 +/- 33,400
      vs. 3,970 +/- 3,495 IU/L; p < 0.001). Acute renal injury occurred in 50% of group
      A and in 26.2% of group B patients. Hemodiafiltration was required in 30% of
      group A and in 9.5% of group B patients. Median follow-up time was 64 months
      (range = 1-130 months). Group A survival was 60% at 1, 5 and 10 years. Group B
      survival was 69% at 1 year and 63.3% at 5 and 10 years (p = 0.15). CONCLUSIONS:
      Aortic injuries associated with MAAVB injuries in major trauma patients seem to
      present in a different clinical scenario. These patients present increased risk
      of rhabdomyolysis, visceral ischemia, and acute renal failure, as well as higher
      in-hospital mortality. A multidisciplinary approach combining endovascular and
      open surgical techniques for a staged treatment of these life-threatening aortic
      and MAAVB injuries is mandatory in this critical subset of trauma patients.

PMID- 22382771
TI  - Preoperative assessment of the pancreas in multiple endocrine neoplasia type 1.
AB  - BACKGROUND: Many serologic and radiographic modalities are used for monitoring
      multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal
      neuroendocrine tumors (PNETs). We compared serum markers and imaging studies
      obtained preoperatively with the gross pathology and immunohistochemical findings
      and correlated preoperative testing with postoperative outcome. METHODS: From
      2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19
      74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies]
      for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide
      (HPP), gastrin, and glucagon] and imaging [CT, (111)In pentetreotide
      scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic
      findings. Postoperative serum markers and survival were followed. RESULTS: Human
      pancreatic polypeptide had the highest agreement between an elevated serum level
      and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67%
      agreement for glucagon). Preoperative CT had 81% sensitivity and positive
      predictive value (PPV) of 97% for PNETs. (111)In pentetreotide scintigraphy had
      84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had
      100% sensitivity and PPV, with close correlation (r (s) = 0.93) between the
      largest lesion seen on EUS and pathology. Median follow-up was 4.3 years (range =
      0.1-10.9 years). Overall survival was 89% at 5-year follow-up. CONCLUSIONS: Our
      study substantiates EUS as providing the highest preoperative sensitivity and PPV
      in assessing the presence of PNETs in MEN 1 patients. CT and octreotide
      scintigraphy can yield both false-positive and false-negative results. HPP,
      gastrin, and glucagon were the most commonly measured tumor markers in our series
      but did not always correlate with immunostaining. With an aggressive surgical
      approach, satisfactory rates of biochemical improvement and long-term survival
      were observed.

PMID- 22382772
TI  - Global surgery rotations for residents.

PMID- 22382773
TI  - Risk factors for chronic pain after open ventral hernia repair by underlay mesh
      placement.

PMID- 22382775
TI  - Transglutaminase 2 transamidation activity during first-phase insulin secretion:
      natural substrates in INS-1E.
AB  - Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent
      transamidating and G protein activity. Previously, we reported that tgm2 -/- mice
      have an impaired insulin secretion and that naturally occurring TG2 mutations
      associated with familial, early-onset type 2 diabetes, show a defective
      transamidating activity. Aim of this study was to get a better insight into the
      role of TG2 in insulin secretion by identifying substrates of TG2 transamidating
      activity in the pancreatic beta cell line INS-1E. To this end, we labeled INS-1E
      that are capable of secreting insulin upon glucose stimulation in the physiologic
      range, with an artificial acyl acceptor (biotinamido-pentylamine) or donor
      (biotinylated peptide), in basal condition and after stimulus with glucose for 2,
      5, and 8 min. Biotinylated proteins were analyzed by two-dimensional
      electrophoresis and mass spectrometry. In addition, subcellular localization of
      TG2 in human endocrine pancreas was studied by electron microscopy. Among several
      TG2's transamidating substrates in INS-1E, mass spectrometry identified
      cytoplasmic actin (a result confirmed in human pancreatic islet), tropomyosin,
      and molecules that participate in insulin granule structure (e.g., GAPDH),
      glucose metabolism, or [Ca(2+)] sensing (e.g., calreticulin). Physical
      interaction between TG2 and cytoplasmic actin during glucose-stimulated first
      phase insulin secretion was confirmed by co-immunoprecipitation. Electron
      microscopy revealed that TG2 is localized close to insulin and glucagon granules
      in human pancreatic islet. We propose that TG2's role in insulin secretion may
      involve cytoplasmic actin remodeling and may have a regulative action on other
      proteins during granule movement. A similar role of TG2 in glucagon secretion is
      also suggested.

PMID- 22382776
TI  - Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update.
AB  - Cisplatin is a highly effective antitumor agent whose clinical application is
      limited by the inherent nephrotoxicity. The current measures of nephroprotection
      used in patients receiving cisplatin are not satisfactory, and studies have
      focused on the investigation of new possible protective strategies. Many pathways
      involved in cisplatin nephrotoxicity have been delineated and proposed as targets
      for nephroprotection, and many new potentially protective agents have been
      reported. The multiple pathways which lead to renal damage and renal cell death
      have points of convergence and share some common modulators. The most frequent
      event among all the described pathways is the oxidative stress that acts as both
      a trigger and a result. The most exploited pathways, the proposed protective
      strategies, the achievements obtained so far as well as conflicting data are
      summarized and discussed in this review, providing a general view of the
      knowledge accumulated with past and recent research on this subject.

PMID- 22382777
TI  - Managing knee injuries: keeping up with changes.

PMID- 22382778
TI  - Evaluation of multiple variate selection methods from a biological perspective: a
      nutrigenomics case study.
AB  - Genomics-based technologies produce large amounts of data. To interpret the
      results and identify the most important variates related to phenotypes of
      interest, various multivariate regression and variate selection methods are used.
      Although inspected for statistical performance, the relevance of multivariate
      models in interpreting biological data sets often remains elusive. We compare
      various multivariate regression and variate selection methods applied to a
      nutrigenomics data set in terms of performance, utility and biological
      interpretability. The studied data set comprised hepatic transcriptome (10,072
      predictor variates) and plasma protein concentrations [2 dependent variates:
      Leptin (LEP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1)] collected
      during a high-fat diet study in ApoE3Leiden mice. The multivariate regression
      methods used were: partial least squares "PLS"; a genetic algorithm-based
      multiple linear regression, "GA-MLR"; two least-angle shrinkage methods, "LASSO"
      and "ELASTIC NET"; and a variant of PLS that uses covariance-based variate
      selection, "CovProc." Two methods of ranking the genes for Gene Set Enrichment
      Analysis (GSEA) were also investigated: either by their correlation with the
      protein data or by the stability of the PLS regression coefficients. The
      regression methods performed similarly, with CovProc and GA performing the best
      and worst, respectively (R-squared values based on "double cross-validation"
      predictions of 0.762 and 0.451 for LEP; and 0.701 and 0.482 for TIMP-1). CovProc,
      LASSO and ELASTIC NET all produced parsimonious regression models and
      consistently identified small subsets of variates, with high commonality between
      the methods. Comparison of the gene ranking approaches found a high degree of
      agreement, with PLS-based ranking finding fewer significant gene sets. We
      recommend the use of CovProc for variate selection, in tandem with univariate
      methods, and the use of correlation-based ranking for GSEA-like pathway analysis
      methods.

PMID- 22382779
TI  - Low serum mannose-binding lectin level is not associated with disease severity in
      non-cystic fibrosis bronchiectasis.
AB  - Deficiency of mannose-binding lectin (MBL), a serum protein involved in killing
      and promoting phagocytosis of pathogens, is associated with respiratory infection
      and disease progression in a number of acute and chronic lung diseases, including
      cystic fibrosis (CF)- associated bronchiectasis. No such association has been
      studied in non-CF bronchiectasis (nCF-Br). One hundred and thirty-three adult
      patients with nCF-Br were studied. Serum MBL levels were measured and deficiency
      defined using two cut-off levels, i.e. MBL <=100 ng/ml and <=600 ng/ml.
      Parameters of severity included lung function impairment, annual exacerbation and
      hospital admission rates, breathlessness, and Pseudomonas aeruginosa and
      Haemophilus influenzae infection rates. The incidence of MBL deficiency using cut
      off levels of 100 ng/ml and 600 ng/ml was 10% and 26% respectively, similar to
      rates seen in the general population. There was no significant difference in mean
      FEV(1)% predicted between MBL deficient and sufficient patients at both cut-off
      levels (<=100 ng/ml: 63.8% vs. 64.6%, P = 0.91; <= 600 ng/ml: 66.5% vs. 63.9%, P
      = 0.56). In addition, exacerbation/hospital admission rates, symptoms of
      breathlessness and isolation/colonisation rates with P. aeruginosa and H.
      influenzae were similar in both groups at both cut-off levels. In conclusion, MBL
      deficiency is not associated with markers of disease severity in patients with
      nCF-Br.

PMID- 22382780
TI  - 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective
      "small molecule" anti-cancer agent taken from labside to bedside: introduction to
      a special issue.
AB  - Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid
      (glycolysis) even in the presence of oxygen, has been recognized as the most
      common biochemical phenotype of cancer for over 80 years, its biochemical and
      genetic basis remained unknown for over 50 years. Work focused on elucidating the
      underlying mechanism(s) of the "Warburg effect" commenced in the author's
      laboratory in 1969. By 1985 among the novel findings made two related most
      directly to the basis of the "Warburg effect", the first that the mitochondrial
      content of tumors exhibiting this phenotype is markedly decreased relative to the
      tissue of origin, and the second that such mitochondria have markedly elevated
      amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is
      the first of a number of enzymes in cancer cells involved in metabolizing the
      sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the
      protein VDAC (voltage dependent anion channel), escapes inhibition by its product
      glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by
      others, it also helps immortalize cancer cells, i.e., prevents cell death. Based
      on these studies, the author's laboratory commenced experiments to elucidate the
      gene basis for the overexpression of HK2 in cancer. These studies led to both the
      discovery of a unique HK2 promoter region markedly activated by both hypoxic
      conditions and moderately activated by several metabolites (e.g., glucose), Also
      discovered was the promoter's regulation by epigenetic events (i.e., methylation,
      demethylation). Finally, the author's laboratory turned to the most important
      objective. Could they selectively and completely destroy cancerous tumors in
      animals? This led to the discovery in an experiment conceived, designed, and
      conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject
      of this mini-review series, is an incredibly powerful and swift acting anticancer
      agent. Significantly, in subsequent experiments with rodents (19 animals with
      advanced cancer) Ko led a project in which 3BP was shown in a short treatment
      period to eradicate all (100%). Ko's and co-author's findings once published
      attracted global attention leading world-wide to many other studies and
      publications related to 3BP and its potent anti-cancer effect. This Issue of the
      Journal of Bioenergetics and Biomembranes (JOBB 44-1) captures only a sampling of
      research conducted to date on 3BP as an anticancer agent, and includes also a
      Case Report on the first human patient known to the author to be treated with
      specially formulated 3BP. Suffice it to say in this bottom line, "3BP, a small
      molecule, results in a remarkable therapeutic effect when it comes to treating
      cancers exhibiting a "Warburg effect". This includes most cancer types.

PMID- 22382781
TI  - Extended adjuvant temozolomide for treatment of newly diagnosed glioblastoma
      multiforme.
AB  - The standard of care for newly diagnosed glioblastoma multiforme (GBM) is
      temozolomide (TMZ) chemotherapy given concurrently with radiation for 6 weeks
      followed by 6 months of adjuvant TMZ. Originally, patients in Alberta were
      treated with only six cycles of adjuvant TMZ regardless of clinical status but
      institutional policy was amended to allow up to 12 cycles of adjuvant therapy for
      patients experiencing at least stable disease and minimal toxicity. We conducted
      a population-based analysis to determine if extended adjuvant TMZ treatment
      (i.e., more than six cycles) confers a survival advantage as compared to the
      standard six cycles for newly diagnosed GBM patients. Patient data was collected
      from the Alberta Cancer Registry and patient charts. Progression free--and
      overall survival was determined in patients receiving six cycles of adjuvant TMZ
      and compared with that of patients receiving more than six cycles. Patients in
      whom adjuvant chemotherapy was stopped at cycle six experienced a median survival
      of 16.5 months, whereas, those who received more than six cycles survived for
      24.6 months (p = 0.031). Extended adjuvant therapy was not associated with
      increased toxicity. In multivariate analysis, adjuvant monthly Temozolomide for
      more than six cycles was an independent prognostic factor for both progression
      free--and overall survival. These data suggest extended adjuvant temozolomide
      (i.e., more than six cycles) should be considered in patients with newly
      diagnosed GBM.

PMID- 22382782
TI  - Knocking down nucleolin expression in gliomas inhibits tumor growth and induces
      cell cycle arrest.
AB  - Nucleolin is a multifunctional protein whose expression often correlates with
      increased cellular proliferation. While the expression of nucleolin is often
      elevated in numerous cancers, its expression in normal human brain and in
      astrocytomas has not been previously reported. Using paraffin-embedded sections
      from normal adult autopsy specimens and glioma resection specimens, we
      demonstrate that nucleolin expression is limited in the normal human brain
      specifically to mature neurons, ependymal cells, and granular cells of the
      dentate gyrus. While astrocytes in the normal human brain do not express
      nucleolin at significant levels, glioblastoma cell lines and primary human
      astrocytoma cells exhibit considerable nucleolin expression. Reduction of
      nucleolin expression through siRNA-mediated knockdown in the U87MG glioblastoma
      cell line caused a dramatic decrease in cell proliferation and induced cell cycle
      arrest in vitro. Moreover, conditional siRNA knockdown of nucleolin expression in
      U87MG intracranial xenografts in nude mice caused dramatic reduction in tumor
      size. Taken together, these results implicate nucleolin in the regulation of
      human astrocytoma proliferation in vitro and tumorigenicity in vivo and suggest
      that nucleolin may represent a potential novel therapeutic target for
      astrocytomas.

PMID- 22382783
TI  - Aurora kinase B/C inhibition impairs malignant glioma growth in vivo.
AB  - Inhibition of Aurora kinase B has been evaluated as a therapy to block solid
      tumor growth in breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and
      colorectal cancer models. Aurora kinase inhibitors are in early clinical trials
      for the treatment of leukemia. We hypothesized that Aurora B inhibition would
      reduce malignant glioma cell viability and result in impaired tumor growth in
      vivo. Aurora B expression is greater in cultured malignant glioma U251 cells
      compared to proliferating normal human astrocytes, and expression is maintained
      in U251 flank xenografts. Aurora B inhibition with AZD1152-HQPA blocked cell
      division in four different p53-mutant glioma cell lines (U251, T98G, U373, and
      U118). AZD1152-HQPA also inhibited Aurora C activation loop threonine
      autophosphorylation at the effective antiproliferative concentrations in vitro.
      Reduction in cell viability of U251 (p53(R273H)) cells was secondary to
      cytokinesis blockade and apoptosis induction following endoreplication. AZD1152
      HQPA inhibited the growth of U251 tumor xenografts and resulted in an increase in
      tumor cell apoptosis both in vitro and in vivo. Subcutaneous administration of
      AZD1152-HQPA (25 mg/kg/day * 4 days; 2 cycles spaced 7 days apart) resulted in a
      prolongation in median survival after intracranial inoculation of U251 cells in
      mice (P = 0.025). This is the first demonstration that an Aurora kinase inhibitor
      can inhibit malignant glioma growth in vivo at drug doses that are clinically
      relevant.

PMID- 22382784
TI  - PROX1 lymphatic density correlates with adverse clinicopathological factors,
      lymph node metastases and survival in neuroblastomas.
AB  - Increased lymphatic density correlates with lymph node metastases and survival in
      some epithelial cancers. The transcription factor, Prospero-related homeobox-gene
      1, PROX1, plays an important role in the differentiation and proliferation of the
      lymphatic and nervous systems. We studied the clinicopathological significance of
      PROX1 expression in neuroblastomas (NBs) as the majority of patients have
      lymphatic and/or haematogenous metastases at diagnosis. PROX1-immunostained
      lymphatic vessels were present in 40/69 (58%) of NBs and 1/6 benign
      ganglioneuromas (GNs). Lymphatic density (LD) counts were significantly increased
      in NBs from patients with unfavourable clinical and pathological factors, and
      with distant lymph node metastases (LNM). Lymphatic invasion (LI) by tumoral
      emboli was present in 27/40 (68%) of NBs. A significantly higher proportion of LI
      was seen in undifferentiated/poorly-differentiated, (UD/PD) compared with
      differentiated NBs. LI was increased in NBs from patients with advanced-stage and
      high-risk group. Nuclear-PROX1 expression in tumoral cells was present in 35/69
      (51%) NBs but was absent in all GNs. PROX1 expression was significantly higher in
      UD/PD compared with differentiated NBs. It was also higher in NBs with all
      adverse clinicopathological and biological variables. LI, PROX1 cellular
      expression and high LD correlated with a shorter overall survival and event-free
      survival (EFS). Multivariable Cox regression analysis showed that the effect of
      LD on both OS and EFS was independent of mitosis-karyorrhexis index and MYCN
      amplification. Increased LD, LI and cellular expression correlated with adverse
      factors in NBs. Increased LD correlated with LNM suggesting that PROX1
      contributes to neuroblastoma progression and lymphatic spread.

PMID- 22382785
TI  - t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by
      activating NF-kappaB-p65.
AB  - Although sEH inhibitors are well studied in inflammatory and cardiovascular
      diseases, their effects on gliomas are unclear. In this study, we investigated
      the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87
      human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell
      line. Our results showed that t-AUCB efficiently inhibited sEH activities in all
      three cell lines (the inhibition rate was more than 80% in each) and suppressed
      U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth
      inhibition on HepG2. We detected high levels of phosphorylated NF-kappaB-p65
      (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-kappaB
      inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This
      indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-kappaB
      p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by
      regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation
      level. We propose to further test this promising reagent for its anti-glioma
      activity in clinical relevant orthotopic brain glioma models.

PMID- 22382786
TI  - Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse
      intrinsic pontine gliomas.
AB  - Despite numerous clinical trials over the past 2 decades, the overall survival
      for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9-10
      months. Radiation therapy is the only treatment with proven effect and novel
      therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is
      the most common variant of the epidermal growth factor receptor and is expressed
      in many tumor types but is rarely found in normal tissue. A peptide vaccine
      targeting EGFRvIII is currently undergoing investigation in phase 3 clinical
      trials for the treatment of newly diagnosed glioblastoma (GBM), the tumor in
      which this variant receptor was first discovered. In this study, we evaluated
      EGFRvIII expression in pediatric DIPG samples using immunohistochemistry with a
      double affinity purified antibody raised against the EGFRvIII peptide. Staining
      of pediatric DIPG histological samples revealed expression in 4 of 9 cases and
      the pattern of staining was consistent with what has been seen in EGFRvIII
      transfected cells as well as GBMs from adult trials. In addition, analysis of
      tumor samples collected immediately post mortem and of DIPG cells in culture by
      RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression.
      We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These
      data suggest that EGFRvIII warrants investigation as a target for these deadly
      pediatric tumors.

PMID- 22382787
TI  - Pharmacokinetic and bioequivalence studies of trospium chloride after a single
      dose administration in healthy Chinese volunteers.
AB  - The study aimed to compare and evaluate the bioequivalence of a new generic
      preparation of trospium chloride (CAS NO:10405-02-4) capsule (20 mg, test) and
      the available import tablet (20 mg , reference) for the requirement of state
      regulatory criteria in China. A randomized- sequence, 2-period crossover study
      was conducted in 20 healthy Chinese male volunteers in the fasted state. Blood
      samples were collected before and 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60 h
      after administration of a single oral dose of 40 mg trospium chloride capsules or
      tablets, followed by a 7-day washout period. The concentration of trospium
      chloride was determined by a LC-MS/MS method. Drug And Statistical-Version 2.0
      was used to calculate the pharmacokinetics parameters and assess bioequivalence
      of the two preparations. It was considered bioequivalent if the 90% CIs of the
      mean ratios (test: reference) for Cmax, AUC0-t and AUC0-infinity were within the
      range from 80% to 125%, respectively. The main pharmacokinetics parameters of
      test and reference were as follows: t1/2 was (15.11 +/- 3.24) h and (16.00 +/-
      3.96) h; Tmax was (4.0 +/- 1.2) h and (4.1 +/- 0.9) h; Cmax was (3.76 +/- 1.87)
      ng.mL - 1 and (3.70 +/- 1.89) ng.mL - 1; AUC0-t was (33.51 +/- 14.39) ng.mL - 1.h
      and (33.33 +/- 14.88) ng.mL - 1.h, and the AUC0-infinity was (35.20 +/- 14.88)
      ng.mL - 1.h and (35.16+/-15.17) ng.mL - 1.h. The ratios (test: reference) for
      Cmax, AUC0-t, and AUC0-infinity were 94.0%~111.7%, 96.4%~106.8%, and
      96.1%~105.3%, respectively. No significant differences in pharmacokinetic
      parameters were found between preparations and periods (p>0.05). No obvious
      adverse events were monitored throughout the study based on clinical parameters
      and patient reports.

PMID- 22382788
TI  - Development of a sensitive bioanalytical method for the quantification of
      lacosamide in rat plasma. Application to preclinical pharmacokinetics studies in
      rats.
AB  - A sensitive and selective high performance liquid chromatographic (HPLC) method
      was developed and validated for quantification of lacosamide in rat plasma. A
      liquid-liquid extraction procedure was optimized to extract lacosamide from rat
      plasma. Chromatographic separation was accomplished using a reversed phase C18
      Hichrom (250*4.6 mm, 5 um) column with the mobile phase consisting of
      acetonitrile-phosphate buffer (pH 3.2+/-0.1; 20 mM) (21:79, v/v) at a flow rate
      of 1 mL/min. Both intra- and inter day assay precision and accuracy were lower
      than 15% CV. The lower limit of quantitation was 25 ng/mL for lacosamide and the
      response was linear in a concentration range from 25 to 10 000 ng/mL. The
      developed method was successfully used for the preclinical pharmacokinetic study
      of lacosamide in rats.

PMID- 22382789
TI  - Interfaces of ionic liquids and transition metal surfaces-adsorption, growth, and
      thermal reactions of ultrathin [C1C1Im][Tf2N] films on metallic and oxidised
      Ni(111) surfaces.
AB  - Ultrathin films of the ionic liquid 1,3-dimethylimidazolium
      bis(trifluoromethylsulfonyl)imide ([C(1)C(1)Im][Tf(2)N]) were deposited on
      differently terminated Ni(111) single crystal surfaces. The initial wetting
      behaviour, the growth characteristics, the molecular arrangement at the
      interface, and thermal reactivity were investigated using angle-resolved X-ray
      photoelectron spectroscopy (ARXPS). On clean Ni(111), the initial growth occurs
      in a layer-by-layer mode. At submonolayer coverages up to at least 0.40 ML, a
      preferential arrangement of the IL ions in a bilayer structure, with the
      imidazolium cations in contact with the Ni surface atoms and the anions on top of
      the cation, is deduced. For higher coverages, a transition to a checkerboard-type
      arrangement occurs, which is most likely due to repulsive dipole-dipole
      interactions in the first layer. An overall preference for a checkerboard-type
      adsorption behaviour, i.e., anions and cations adsorbing next to each other, is
      found on the oxygen-precovered O(?3*?3)R30 degrees  Ni(111) surface. The thermal
      stability of adsorbed IL layers on Ni(111) and on a fully oxidised Ni(111)
      surface was studied by heating the layers to elevated temperatures. For clean
      Ni(111) reversible adsorption takes place. For the oxidised surface, however,
      only cation-related moieties desorb, starting at ~450 K, while anion-related
      signals remain on the surface up to much higher temperatures.

PMID- 22382790
TI  - Take care of yourself.

PMID- 22382791
TI  - Infusion Nursing Standards of Practice influences the Boards of Registration in
      Nursing on advisory rulings regarding peripherally inserted central catheters.

PMID- 22382792
TI  - Intravenous therapy: a review of complications and economic considerations of
      peripheral access.
AB  - Despite the growing frequency of intravenous (IV) injections, establishing
      peripheral IV access is challenging, particularly in patients with small or
      collapsed veins. Therefore, patients often endure failed attempts and eventually
      become venous depleted. Furthermore, maintaining patients' vascular access
      throughout treatment is difficult because a number of complications including
      phlebitis, infiltration, extravasation, and infections can occur. The aim of this
      article is to review the use of the IV route for administering therapy, identify
      and analyze key risks and complications associated with achieving and maintaining
      peripheral IV access, examine measures to reduce these risks, and discuss
      implications for nurses in clinical practice.

PMID- 22382793
TI  - A randomized double-blind study comparing intradermal anesthetic tolerability,
      efficacy, and cost-effectiveness of lidocaine, buffered lidocaine, and
      bacteriostatic normal saline for peripheral intravenous insertion.
AB  - In this double-blind study, 256 surgical patients meeting eligibility criteria
      were randomized in a 1:1:1 ratio to 1 of the 3 intradermal injection groups prior
      to intravenous (IV) line insertion (Group 1=1% lidocaine, Group 2=1% buffered
      lidocaine, and Group 3=bacteriostatic normal saline with a benzyl alcohol
      preservative). The most tolerable solution, as measured by the average level of
      pain from an intradermal insertion, was buffered lidocaine (Group 2). The most
      efficacious, as measured by average level of pain at IV cannulation, were Groups
      1 and 2. Group 3 was the most cost-effective.

PMID- 22382794
TI  - Applying the novice-to-expert model to infusion nursing.
AB  - The novice-to-expert continuum serves as the basis for many development and
      advancement models. Consideration of the intent of the model, domains, and
      characteristics of practice, a foundation in reflective practice, and
      implications for educators are essential for successful implementation of a
      novice-to-expert model. An example of a long-standing novice-to-expert model and
      application of a novice-to-expert model to infusion nursing are discussed.

PMID- 22382795
TI  - Development of a compatibility chart for intravenous Y-site drug administration
      in a pediatric intensive care unit.
AB  - Pediatric patients admitted to intensive care units are likely candidates for
      intravenous drug administration. These patients may sometimes have limited
      vascular access, so availability of compatibility charts for intravenous Y-site
      administration may help daily clinical practice. A 2-dimensional table with the
      47 intravenous drugs more commonly administered in the authors' pediatric
      intensive care unit was drawn up based on a review of 4 databases routinely used
      for checking drug compatibilities. The level of concordance between the various
      sources used for the review was strong (kappa>0.8). However, an awareness of the
      limitations of each of these databases will help to optimize search results.

PMID- 22382797
TI  - Synthesis and characterization of colloidal gold particles as labels for
      antibodies as used in lateral flow devices.
AB  - Based on well established citrate reduction protocols for the synthesis of
      colloidal gold particles, this work focuses on the characterization of these
      colloids for further use as color labels in lateral flow devices. A reproducible
      production method has been developed for the synthesis of well characterized
      colloidal gold particles to be employed in Lateral Flow Devices (LFDs). It has
      been demonstrated that when undertaking chemical reduction of gold salts with
      sodium citrate, the amount of reducing agent employed could be used to directly
      control the size of the resultant particles. A protocol was thereby developed for
      the synthesis of colloidal gold particles of pre-defined diameters in the range
      of 15 to 60 nm and of consistent size distribution. The absorption maxima
      (lambda(max)) of the reaction solutions were analyzed by UV/VIS measurements to
      determine approximate particle sizes, which were confirmed with transmission
      electron microscopy (TEM) measurements. Colloidal gold particles of about 40 nm
      in diameter were synthesized and used for labeling monoclonal anti-mycotoxin
      antibodies (e.g. zearalenone). To deduce the extent of antibody coupling to these
      particles, smaller colloids with 15 nm diameter were labeled with anti-species
      specific antibodies. Both solutions were mixed and then scanned by TEM to obtain
      information about the success of coupling.

PMID- 22382798
TI  - Microfluidics meets soft layer-by-layer films: selective cell growth in 3D
      polymer architectures.
AB  - We present here the micropatterns of layer-by-layer (LbL) assembled soft films
      generated using microfluidic platform that can be exploited for selective cell
      growth. Using this method, the issue of cell adhesion and spreading on soft LbL
      derived films, and simultaneous utilisation of such unmodified soft films to
      exploit their reservoir properties are addressed. This also paves the way for
      extending the culture of cells to soft films and other demanding applications
      like triggered release of biomolecules.

PMID- 22382799
TI  - Thrombophilia screening in young patients with cryptogenic stroke. Prevalence of
      gene polymorphisms compared to healthy blood donors and impact on secondary
      stroke prevention.
AB  - The clinical relevance of thrombophilia screening in stroke patients is still a
      matter of debate, and descriptions of larger patterns of genetic variability are
      rare. We assessed the frequency of hereditary hypercoagulability in young
      patients with cryptogenic stroke (n = 44) and in healthy blood donors (n = 282)
      without prior cardiovascular event. Furthermore, we focused on the impact of
      thrombophilia screening on secondary stroke prevention. RESULTS: Compared to the
      control group (19-67 years; median 38.5 years; 64% women), there was a lower
      prevalence of the FVII-R353Q mutation (p = 0.033) in stroke patients (17-52
      years; median 36 years; 59.1% women). Of note, the FVII-R353Q mutation lowers
      FVII plasma levels, probably reducing the risk of cardiovascular events. The
      prevalence of the remaining 13 gene polymorphisms did not differ significantly.
      However, the prevalence of FV Leiden mutation tended to be higher among stroke
      patients. CONCLUSION: Overall, extended screening for inherited thrombophilia had
      an impact on medical stroke prevention in every sixth patient with cryptogenic
      stroke.

PMID- 22382800
TI  - Return of individual research results and incidental findings in the clinical
      trials cooperative group setting.
AB  - The National Cancer Institute (NCI)-funded cooperative group cancer clinical
      trial system develops experimental therapies and often collects samples from
      patients for correlative research. The cooperative group bank (CGB) system
      maintains biobanks with a current policy not to return research results to
      individuals. An online survey was created, and 10 directors of CGBs completed the
      surveys asking about understanding and attitudes in changing policies to consider
      return of incidental findings (IFs) and individual research results (IRRs) of
      health significance. The potential impact of the 10 consensus recommendations of
      Wolf et al. presented in this issue are examined. Reidentification of samples is
      often not problematic; however, changes to the current banking and clinical trial
      systems would require significant effort to fulfill an obligation of recontact of
      subjects. Additional resources, as well as a national advisory board would be
      required to standardize implementation.

PMID- 22382801
TI  - Mapping the inputs, analyses, and outputs of biobank research systems to identify
      sources of incidental findings and individual research results for potential
      return to participants.
AB  - Progress in the debate over returning incidental findings (IFs) and individual
      research results (IRRs) to research participants who provide specimens and data
      to biobanks in genetic and genomic research requires a new tool to allow
      comparison across heterogeneous biobank research systems and in-depth analysis of
      the sources and types of findings generated for potential return. This article
      presents a new visual mapping tool to allow systematic and standardized depiction
      of (i) the specimens initially collected, (ii) the materials and data sets then
      created, (iii) the analyses then performed, and finally (iv) the genetic and
      genomic results generated, including potential IFs and IRRs. For any individual
      biobank research system, this sequence of four maps can be created to anticipate
      the sources and types of IFs and IRRs to be generated, to plan how to handle
      them, and then to manage them responsibly over time. We discuss how this four-map
      tool was created and describe its application to four national biobank systems,
      thereby demonstrating that this tool can provide a common platform to visualize
      biobank content, anticipate how IFs and IRRs will arise in a biobank research
      context, and inform policy development.

PMID- 22382802
TI  - Exon-level array CGH in a large clinical cohort demonstrates increased
      sensitivity of diagnostic testing for Mendelian disorders.
AB  - PURPOSE: Mendelian disorders are most commonly caused by mutations identifiable
      by DNA sequencing. Exonic deletions and duplications can go undetected by
      sequencing, and their frequency in most Mendelian disorders is unknown. METHODS:
      We designed an array comparative genomic hybridization (CGH) test with probes in
      exonic regions of 589 genes. Targeted testing was performed for 219 genes in
      3,018 patients. We demonstrate for the first time the utility of exon-level array
      CGH in a large clinical cohort by testing for 136 autosomal dominant, 53
      autosomal recessive, and 30 X-linked disorders. RESULTS: Overall, 98 deletions
      and two duplications were identified in 53 genes, corresponding to a detection
      rate of 3.3%. Approximately 40% of positive findings were deletions of only one
      or two exons. A high frequency of deletions was observed for several autosomal
      dominant disorders, with a detection rate of 2.9%. For autosomal recessive
      disorders, array CGH was usually performed after a single mutation was identified
      by sequencing. Among 138 individuals tested for recessive disorders, 10.1% had
      intragenic deletions. For X-linked disorders, 3.5% of 313 patients carried a
      deletion or duplication. CONCLUSION: Our results demonstrate that exon-level
      array CGH provides a robust option for intragenic copy number analysis and should
      routinely supplement sequence analysis for Mendelian disorders.

PMID- 22382803
TI  - Tilting at windmills no longer: a data-driven discussion of DTC DNA ancestry
      tests.
AB  - PURPOSE: Discussions about direct-to-consumer (DTC) DNA ancestry tests have to
      date been based primarily on conjectures, speculation, and anecdotes, despite the
      industry being more than a decade old. Representative, empirical data on consumer
      characteristics; motivations and expectations for testing; intended uses for the
      information; understanding of results; and behavioral and psychological reactions
      to the tests are absent. Although the 2010 American Society of Human Genetics
      white paper clarifies the number and some general characteristics of companies
      marketing and selling DNA ancestry tests, additional data about the industry's
      practices have been unavailable. METHODS: To promote a data-driven discussion of
      the DNA ancestry testing industry, we conducted a systematic investigation to
      identify companies selling DNA ancestry tests and conducted an empirical study of
      the industry's practices using data collected from each company's website.
      RESULTS: Here, we present a wealth of data, including an updated directory of
      companies, marketing slogans, product types and names, range of prices, diversity
      of reporting and representing results, noted benefits and limitations of testing,
      and a host of website practices. CONCLUSION: The tremendous diversity of tests,
      information, and practices of companies in the DNA ancestry sector should be
      considered when policies for best practice guidelines or regulatory oversight are
      being developed.

PMID- 22382804
TI  - Impact of family caregiving by youth on their psychological well-being: a latent
      trait analysis.
AB  - Secondary data analyses were conducted on a survey dataset from 1,281 middle
      school students to analyze the impact of family caregiving on self-reports of
      psychological well-being using the Multiple Indicators, Multiple Causes (MIMIC)
      model. Factor analysis resulted in four latent factors underlying psychological
      functioning, and the MIMIC model revealed significant caregiver effects on three
      factors: anxiety/depression, engaged coping, and disengaged coping, but not life
      satisfaction. Youth caregivers, especially those living with the care recipient,
      reported significantly higher anxiety/depression and a greater use of both coping
      styles compared to non-caregivers. Caregiving has a negative influence on the
      emotional well-being of youth with dual student-caregiver roles. The utilization
      of more coping strategies may reflect needing to try many approaches to
      school/family stressors because supports and experience are limited. Research to
      clarify how caregiving mediates the behavioral health and academic success of
      youth and also impacts care recipients and the family is warranted.

PMID- 22382805
TI  - Applying social and cultural capital frameworks: understanding employment
      perspectives of transition age youth with serious mental health conditions.
AB  - Vulnerable transition age youth, such as those in foster care and with serious
      mental health conditions, are at increased risk for lower rates of employment.
      Social capital is empirically linked to employment in the general population, yet
      little is known about the role of social capital in employment for at-risk
      transition age youth. Focus groups were conducted with young people with serious
      mental health conditions and their vocational specialists. Discussions reveal
      that both social and cultural capital influence employment processes. Those with
      employment experience value the motivation to work provided through others
      compared to those with no employment experience. Consistently employed describe
      strong working relationships with vocational specialists and possession of self
      awareness, professionalism, and work-place knowledge as critical for employment
      success, while inconsistently employed describe worries about controlling
      emotions or behaviors on the job. Building social and cultural capital are
      explored as potential service provider goals.

PMID- 22382807
TI  - Design of energy band alignment at the Zn(1-x)Mg(x)O/Cu(In,Ga)Se2 interface for
      Cd-free Cu(In,Ga)Se2 solar cells.
AB  - The electronic band structure at the Zn(1-x)Mg(x)O/Cu(In(0.7)Ga(0.3))Se(2)
      interface was investigated for its potential application in Cd-free
      Cu(In,Ga)Se(2) thin film solar cells. Zn(1-x)Mg(x)O thin films with various Mg
      contents were grown by atomic layer deposition on Cu(In(0.7)Ga(0.3))Se(2)
      absorbers, which were deposited by the co-evaporation of Cu, In, Ga, and Se
      elemental sources. The electron emissions from the valence band and core levels
      were measured by a depth profile technique using X-ray and ultraviolet
      photoelectron spectroscopy. The valence band maximum positions are around 3.17 eV
      for both Zn(0.9)Mg(0.1)O and Zn(0.8)Mg(0.2)O films, while the valence band
      maximum value for CIGS is 0.48 eV. As a result, the valence band offset value
      between the bulk Zn(1-x)Mg(x)O (x = 0.1 and x = 0.2) region and the bulk CIGS
      region was 2.69 eV. The valence band offset value at the Zn(1-x)Mg(x)O/CIGS
      interface was found to be 2.55 eV after considering a small band bending in the
      interface region. The bandgap energy of Zn(1-x)Mg(x)O films increased from 3.25
      to 3.76 eV as the Mg content increased from 0% to 25%. The combination of the
      valence band offset values and the bandgap energy of Zn(1-x)Mg(x)O films results
      in the flat (0 eV) and cliff (-0.23 eV) conduction band alignments at the
      Zn(0.8)Mg(0.2)O/Cu(In(0.7)Ga(0.3))Se(2) and
      Zn(0.9)Mg(0.1)O/Cu(In(0.7)Ga(0.3))Se(2) interfaces, respectively. The
      experimental results suggest that the bandgap energy of Zn(1-x)Mg(x)O films is
      the main factor that determines the conduction band offset at the Zn(1
      x)Mg(x)O/Cu(In(0.7)Ga(0.3))Se(2) interface. Based on these results, we conclude
      that a Zn(1-x)Mg(x)O film with a relatively high bandgap energy is necessary to
      create a suitable conduction band offset at the Zn(1-x)Mg(x)O/CIGS interface to
      obtain a robust heterojunction. Also, ALD Zn(1-x)Mg(x)O films can be considered
      as a promising alternative buffer material to replace the toxic CdS for
      environmental safety.

PMID- 22382808
TI  - Interventional radiology of male varicocele: current status.
AB  - Varicocele is a fairly common condition in male individuals. Although a minor
      disease, it may cause infertility and testicular pain. Consequently, it has high
      health and social impact. Here we review the current status of interventional
      radiology of male varicocele. We describe the radiological anatomy of gonadal
      veins and the clinical aspects of male varicocele, particularly the physical
      examination, which includes a new clinical and ultrasound Doppler maneuver. The
      surgical and radiological treatment options are also described with the focus on
      retrograde and antegrade sclerotherapy, together with our long experience with
      these procedures. Last, we compare the outcomes, recurrence and persistence
      rates, complications, procedure time and cost-effectiveness of each method. It
      clearly emerges from this analysis that there is a need for randomized
      multicentre trials designed to compare the various surgical and percutaneous
      techniques, all of which are aimed at occlusion of the anterior pampiniform
      plexus.

PMID- 22382806
TI  - Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients
      with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study.
AB  - Prevalence and phenotype of BRCA mutation can vary by race. The purpose of this
      study is to evaluate the prevalence of BRCA1/2 mutations in non-familial breast
      cancer patients with high risks in Korea. A subset of 758 patients was selected
      for this study from the KOHBRA nationwide multicenter prospective cohort study.
      Mutations in BRCA1/2 genes were tested using fluorescent-conformation sensitive
      gel electrophoresis, denaturing high performance liquid chromatography or direct
      sequencing. Mutation of BRCA1/2 genes were identified in 65 (8.6%) patients among
      total 758 patients [BRCA1 mutation: 25 (3.3%), BRCA2 mutation: 40 (5.3%)].
      According to risk groups, mutation of BRCA1/2 genes were identified in 53 (8.5%)
      of 625 early onset patients (age <= 40), in 22 (17.7%) of 124 bilateral breast
      cancer patients, in 3 (50.0%) of 6 breast and ovarian cancer patients, in one
      (5.9%) of 17 male breast cancer patients, in 5 cases (7.6%) of 66 multiple organ
      cancer patients. The most common mutation was 509C>A for BRCA1 and 7708C>T for
      BRCA2. The prevalence of BRCA1/2 mutations by age in early onset patients was
      significantly different (age <35 vs age >=35; 10.0 vs 2.9%, p = 0.0007). BRCA1/2
      mutations for non-familial Korean breast cancer patients were detected at a high
      rate, particularly, in patients with early onset of less than 35 years of age,
      bilateral breast cancer, and breast and ovarian cancer. Individualized genetic
      counseling should be offered for non-familial breast cancer patients with these
      risk factors.

PMID- 22382809
TI  - Supraumbilical subcutaneous fat necrosis after transcatheter arterial
      chemoembolization with drug-eluting beads: case report and review of the
      literature.

PMID- 22382810
TI  - Oenocyte development in the red flour beetle Tribolium castaneum.
AB  - Oenocytes are a specialized cell type required for lipid processing, pheromone
      secretion, and developmental signaling. Their development has been well
      characterized in Drosophila melanogaster, but it remains unknown whether the
      developmental program is conserved in other insect species. In this study, we
      compare and contrast the specification and development of larval oenocytes
      between Drosophila and the red flour beetle, Tribolium castaneum. First, we
      identify several useful reagents to label larval oenocytes, including both a
      Tribolium GFP enhancer trap line and a simple flurophore-conjugated streptavidin
      staining method that recognizes oenocytes across insect species. Second, we use
      these tools to describe oenocyte development in Tribolium embryos, and our
      findings provide evidence for conserved roles of MAP kinase signaling as well as
      the Spalt, Engrailed, hepatocyte nuclear factor-4, and ventral veins lacking
      factors in producing abdominal-specific oenocyte cells. However, Tribolium
      embryos produce four times as many oenocytes per abdominal segment as Drosophila,
      and unlike in Drosophila, these cells rapidly downregulate the expression of the
      Spalt transcription factor. Thus, these results provide new insight into the
      molecular pathways regulating oenocyte specification across insect species.

PMID- 22382811
TI  - A multicenter phase II study of TSU-68, an oral multiple tyrosine kinase
      inhibitor, in combination with docetaxel in metastatic breast cancer patients
      with anthracycline resistance.
AB  - BACKGROUND: TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits
      vascular endothelial growth factor receptor-2, platelet-derived growth factor
      receptor, and fibroblast growth factor receptor. This open-label, non
      comparative, multicenter phase II study evaluated TSU-68 in combination with
      docetaxel in patients with metastatic breast cancer that had relapsed within 1
      year despite prior treatment with an anthracycline-containing regimen. METHODS:
      TSU-68 was orally administered on days 1-21, and docetaxel was intravenously
      delivered on day 1. The regimen was repeated every 21 days. Primary endpoint was
      objective response rate according to the RECIST guidelines version 1.0. RESULTS:
      TSU-68 in combination with docetaxel produced objective responses in 21.1% and
      clinical benefits in 42.1% of the patients, respectively (1 complete response, 3
      partial response, and 4 stable disease for at least 24 weeks, n = 19). Median
      time to progression was 148 days, and median overall survival was 579 days. The
      common adverse drug reactions were leukopenia, neutropenia, nail disorder,
      malaise, dysgeusia, alopecia, and edema. CONCLUSIONS: TSU-68 in combination with
      docetaxel showed a promising antitumor response with manageable toxicity in
      patients with anthracycline-resistant metastatic breast cancer. Further studies
      are warranted in a different population of breast cancer or other solid cancers.

PMID- 22382812
TI  - Metastatic breast carcinoma of the abdominal wall muscle: a case report.
AB  - Metastasis from breast carcinoma is an uncommon occurrence in skeletal muscle,
      compared to local invasion into muscle from direct tumor spread. A 49-year-old
      woman was referred to our hospital with an 8.5-cm mass in the right breast. Core
      needle biopsy revealed metaplastic carcinoma with squamous metaplasia. The mass
      was rapidly growing and metaplastic, so mastectomy with dissection of axillary
      lymph nodes was performed. Pathological examination showed metaplastic carcinoma,
      histological grade 3, triple negative, and a MIB-1 labeling index of 80%. Six
      months postoperatively, during adjuvant chemotherapy treatment, she reported
      numbness and pain in the right lateral thigh and a mass in the right lower
      abdomen. Computed tomography revealed multiple lined masses in the abdominal wall
      and iliac muscle. Core needle biopsy showed metastatic breast carcinoma. Radio-
      and chemotherapy were administered, but the mass in the muscle became enlarged.
      To control her pain, a combined treatment with morphine, fentanyl, ketamine,
      antiepilepsy drug, and NSAIDs was administered. Liver metastasis appeared 9
      months (15 months postoperatively) after recognition of muscle metastasis, and
      the patient died 16 months postoperatively. Skeletal muscle metastasis is
      uncommon, and therapeutic intervention is mainly palliative. The most common
      symptom of skeletal muscle metastasis is pain; thus, pain control is a pivotal
      goal of treatment.

PMID- 22382813
TI  - Rats with different thresholds to clonic convulsions induced by DMCM differ in
      the binding of [3H]-MK-801 and [3H]-ouabain in the membranes of brain regions.
AB  - Considering the putative participation of N-methyl-D-aspartate (NMDA) receptors
      and the Na(+), K(+)-ATPase enzymes in the susceptibility to convulsions induced
      by the benzodiazepine inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline
      3-carboxylate (DMCM), the present study sought to determine if rats with high
      (HTR) and low (LTR) thresholds to clonic convulsions induced by DMCM differed in
      the following aspects: the binding of NMDA receptors by [(3)H]-MK-801, Na(+),
      K(+)-ATPase activity (K(+)-stimulated p-nitrophenylphosphatase) and high-affinity
      [(3)H]-ouabain binding to membranes from discrete brain regions. Compared to the
      HTR subgroup, the LTR subgroup presented a lower binding of [(3)H]-MK-801 in the
      hippocampus, frontal cortex and striatum. The subgroups did not differ in K(+)-p
      nitrophenylphosphatase activity, but the LTR subgroup had a lower density of
      isozymes with a high-affinity to ouabain in the brainstem and in the frontal
      cortex and a lower affinity to ouabain in the hippocampus than the HTR subgroup.
      These results suggest that NMDA receptors and ouabain-sensitive Na(+), K(+)
      ATPase isozymes may underlie the susceptibility to DMCM-induced convulsions.

PMID- 22382814
TI  - Myricetin facilitates potassium currents and inhibits neuronal activity of PVN
      neurons.
AB  - The effects of myricetin on hypothalamic paraventricular nucleus (PVN) neurons in
      rats were investigated. By whole-cell patch clamp detection in hypothalamic brain
      slices, we showed that the action potential frequency in type-I PVN neurons dose
      dependently decreased after myricetin treatment. Further studies demonstrated
      that myricetin may enhance potassium currents and shifts the voltage-dependence
      of activation of potassium currents to more negative potentials by 6.07 mV. Using
      calcium free/cadmium perfusion solution could reverse myricetin-induced
      enhancement of potassium currents in PVN neurons. These results suggested that
      inhibition of hypothalamic PVN neurons by myricetin might be attributed to the
      enhancement of potassium currents.

PMID- 22382815
TI  - MOFs as multifunctional catalysts: one-pot synthesis of menthol from citronellal
      over a bifunctional MIL-101 catalyst.
AB  - A bifunctional MOF catalyst containing coordinatively unsaturated Cr(3+) sites
      and palladium nanoparticles (Pd@MIL-101) has been used for the cyclization of
      citronellal to isopulegol and for the one-pot tandem isomerization/hydrogenation
      of citronellal to menthol. The MOF was found to be stable under the reaction
      conditions used, and the results obtained indicate that the performance of this
      bifunctional solid catalyst is comparable with other state-of-the-art materials
      for the tandem reaction: Full citronellal conversion was attained over Pd@MIL-101
      in 18 h, with 86% selectivity to menthols and a diastereoselectivity of 81% to
      the desired (-)-menthol, while up to 30 h were necessary for attaining similar
      values over Ir/H-beta under analogous reaction conditions.

PMID- 22382816
TI  - Previous healthcare exposure is the main antecedent for methicillin-resistant
      Staphylococcus aureus carriage on hospital admission in Belgium.
AB  - This study aimed to estimate the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) carriage upon hospital admission and to study the
      molecular epidemiology of MRSA in order to assess the proportion of Panton
      Valentine leukocidin (PVL)-positive community-associated (CA) and livestock
      associated (LA) MRSA strains. Epidemiological data on MRSA carriage upon hospital
      admission (2006-2009) were collected in a compulsory, continuous, national MRSA
      surveillance in Belgian acute-care hospitals. Additionally, 328 MRSA strains in
      2005 and 314 strains in 2008 were collected in a separate, multicenter
      microbiological survey. Spa-typing, SCCmec-typing and MLST were performed; toxin
      genes were detected by PCR. The overall prevalence of MRSA carriage upon hospital
      admission was 8.9 cases/1,000 admissions between 2006 and 2009. Of MRSA carriers,
      37.5% had a known MRSA history, 39.4% had stayed in a care facility, 12.2%
      reported no contact with healthcare. Over 90% of MRSA belonged to five healthcare
      associated clones. Of these, MRSA spa-CC038-ST45-IV was in decline, mainly in
      favor of spa-CC008-ST8-IV. MRSA spa-CC002-ST5-IV, spa-CC002-ST5-II and spa-CC032
      ST22-IV remained relatively stable. The proportion of PVL-positive CA-MRSA and LA
      MRSA ST398 was below 2% of all MRSA. The extra-hospital MRSA reservoir in Belgium
      mainly consists of persons with previous healthcare exposure. PVL-positive CA
      MRSA and LA-MRSA strains remained infrequent among hospitalized patients.

PMID- 22382817
TI  - Teenagers' knowledge about HPV infection and HPV vaccination in the first year of
      the public vaccination programme.
AB  - The aim of this study was to assess teens' knowledge of HPV infection and
      vaccination one year after the initiation of the public vaccination programme and
      information campaign on the disease and the opportunity of vaccination. Between
      15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending
      high schools in a town in the northeast of Italy by means of an anonymous and
      unannounced questionnaire covering the knowledge of HPV infection, transmission,
      prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew
      what HPV infection is (92% of girls vs 51% of boys, p < 0.001); only 70% knew
      that it is a sexually-transmitted infection. Only 69.3% associated condoms with
      HPV disease prevention (72.6% girls vs 61.5% boys, p = 0.002). About 18.8% of
      girls and 33.2% of boys believe that HPV can lead to AIDS (p < 0.001). Among
      teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it
      can prevent AIDS (p < 0.001). Only 75.5% of girls and 51.1% of boys (p < 0.001)
      believe that condom use remains useful for HPV prevention after vaccination. The
      need for regular pap smears after vaccination is reported by 93.3% of girls.
      Teens' knowledge about HPV infection and vaccination remains insufficient,
      despite a broad information campaign. Erroneous information may increase risky
      sexual behaviours. Without complete information about HPV infection and
      vaccination and information about other sexually-transmitted diseases, the latter
      might become difficult to control among teenagers, while some misunderstandings
      about the usefulness of secondary prevention might linger.

PMID- 22382818
TI  - Pediculosis capitis: new insights into epidemiology, diagnosis and treatment.
AB  - Pediculosis capitis is a ubiquitous parasitic skin disease caused by Pediculus
      humanus capitis. Head lice are highly specialised parasites which can propagate
      only on human scalp and hair. Transmission occurs by direct head-to-head contact.
      Head lice are vectors of important bacterial pathogens. Pediculosis capitis
      usually occurs in small epidemics in play groups, kindergartens and schools.
      Population-based studies in European countries show highly diverging prevalences,
      ranging from 1% to 20%. The diagnosis of head lice infestation is made through
      the visual inspection of hair and scalp or dry/wet combing. The optimal method
      for the diagnosis of active head lice infestation is dry/wet combing. Topical
      application of a pediculicide is the most common treatment. Compounds with a
      neurotoxic mode of action are widely used but are becoming less effective due to
      resistant parasite populations. Besides, their use is restricted by safety
      concerns. Dimeticones, silicone oils with a low surface tension and the
      propensity to perfectly coat surfaces, have a purely physical mode of action.
      This group of compounds is highly effective and safe, and there is no risk that
      head lice become resistant. The control of epidemics requires active contact
      tracing and synchronised treatment with an effective and safe pediculicide.

PMID- 22382819
TI  - Identification of Francisella tularensis by both culture and real-time TaqMan PCR
      methods from environmental water specimens in outbreak areas where tularemia
      cases were not previously reported.
AB  - Tularemia is an endemic disease in Turkey. In this study, we aimed to detect
      Francisella tularensis by two methods from natural water supplies thought to
      cause tularemia epidemiologically. A total of 154 water specimens from three
      different outbreaks caused by drinking water were collected. Water specimens were
      cultured on antibiotic-added cysteine heart agar base with blood and incubated at
      37 degrees C in a humidified atmosphere containing 5% CO(2) for 4-10 days. The
      suspected colonies were confirmed by F. tularensis antiserum (BD) and the real
      time TaqMan polymerase chain reaction (PCR) method. DNA was isolated from samples
      obtained from filters. The primer and probe sets targeting the ISFtu2 genome were
      used. A total of four F. tularensis isolates were obtained from 154 water
      samples. At the same time, the presence of F. tularensis DNA from 17 water
      specimens was shown by the real-time TaqMan PCR method. Although the DNA presence
      of F. tularensis has been detected from water sources by the PCR method in Turkey
      up to now, there has been no isolation directly from water specimens by culture.
      In this study, the determination of F. tularensis from water sources has been
      exhibited as the first data by both culture and real-time TaqMan PCR methods.

PMID- 22382820
TI  - Severe cochlear inflammation and vestibular syndrome in an experimental model of
      Streptococcus suis infection in mice.
AB  - Hearing impairment is a common and frequently permanent sequel of Streptococcus
      suis meningitis in humans. Nevertheless, mechanisms underlying the development of
      cochlear damage have not been addressed so far. In the present work, we
      characterized a mouse model of suppurative labyrinthitis and meningitis induced
      by a systemic infection with S. suis and studied the impact of the injected
      bacterial dosage on the progression of such inflammatory events. We observed that
      high infection doses of bacteria lead to sustained bacteremia, with an increase
      in the permeability of the blood-labyrinth and blood-brain barriers, causing
      suppurative labyrinthitis and meningitis, respectively. However, in mice infected
      with a low dose of S. suis, bacteria disappeared quickly from blood, hence,
      cochlear inflammation and meningitis were not consistent features. This model of
      S. suis infection seems ideal to evaluate novel drugs that may help alleviate the
      negative consequences of such important sequelae of S. suis-induced meningitis
      and labyrinthitis.

PMID- 22382821
TI  - Human papillomavirus viral load expressed as relative light units (RLU)
      correlates with the presence and grade of preneoplastic lesions of the uterine
      cervix in atypical squamous cells of undetermined significance (ASCUS) cytology.
AB  - Human papillomavirus (HPV) testing is more sensitive and has higher negative
      predictive value (NPV) than the Pap test for the detection of cervical
      intraepithelial neoplasia (CIN) in patients with atypical squamous cells of
      undetermined significance (ASCUS) cytology, but has low specificity, leading to
      high referral rates to second-level triage. Our goal was to identify the
      prognostic significance of HPV viral load figures. We evaluated whether a
      correlation between viral load, expressed as relative light units/cutoff
      (RLU/CO), and the severity of cervical lesions existed in 614 ASCUS cases. Hybrid
      Capture 2 (HC2(r)) RLU/CO values, categorised into five classes, were correlated
      to clinical outcomes and statistically analysed. A significant correlation (p <
      0.0001) was observed between increasing RLU values and the prevalence of high
      grade CIN (CIN2/CIN3). The mean RLU values for negative, low-grade and high-grade
      lesions were 68.1, 172.5 and 1,020.0 RLU/CO, respectively (p < 0.0001). CIN2/CIN3
      ranged from 4% for 0 < RLU/CO values <= 1, to 5% for 1 < RLU/CO values <= 10, to
      9% for 10 < RLU/CO values <= 100, to 23% for 100 < RLU/CO values <= 1,000 and to
      48% when RLU/CO values were >1,000 (p < 0.05). The HPV viral load in ASCUS cases
      significantly correlates with the severity of cervical cancer precursors. These
      data may have prognostic value, as they significantly correlate with the
      probability of a CIN2+ .

PMID- 22382822
TI  - Umbilical cord blood procalcitonin as a risk factor for mortality in very
      premature infants.
AB  - Fetal inflammatory response syndrome is implicated as a cause of fetal or
      neonatal injury. We analyzed the relationship between the procalcitonin umbilical
      cord blood level and neonatal outcome. A total of 237 preterms born in a level
      III perinatal medicine unit of a French university hospital were enrolled in a
      prospective observational study. Measurement of the procalcitonin umbilical cord
      blood level was performed at birth. After hospitalization, surviving infants were
      enrolled in the regional follow-up program. Outcome data were recorded on
      standardized questionnaires. The main outcome measures were neonatal mortality
      and impaired functional outcome at 2 years of corrected age. The terciles of
      procalcitonin levels were calculated. Preterm infants of the third tercile were
      defined as infants with elevated procalcitonin. Among the 237 infants, 13 (5.5%)
      died during the neonatal period, 20 (8.4%) were lost to follow-up, and 31 (13.1%)
      were classified as having an impaired functional outcome. After adjustment,
      elevated cord blood procalcitonin (>0.33 ng/ml) was significantly associated with
      an increase in mortality (adjusted odds ratio [aOR] = 8.3 [1.4-48]; p = 0.018),
      but not with the 2-year impaired functional outcome (aOR = 1.0 [0.4-2.5]; p =
      0.93). Elevated umbilical blood cord procalcitonin concentration is an
      independent risk factor of mortality in preterm infants at less than 33 weeks'
      gestation.

PMID- 22382823
TI  - Formal infectious diseases consultation is associated with decreased mortality in
      Staphylococcus aureus bacteraemia.
AB  - To determine the impact of infectious diseases consultation (IDC) in
      Staphylococcus aureus bacteraemia. All MRSA bacteraemia and a random subset of
      MSSA bacteraemia were retrospectively analysed. Out of 599 SAB episodes, 162
      (27%) were followed by an IDC. Patients with IDC were younger and more frequently
      intravenous drug users, but fewer resided in a long-term care facility or were
      indigenous. Hospital length of stay was longer (29.5 vs 17 days, p < 0.001), and
      endocarditis (19.1% vs 7.3%, p < 0.001) and metastatic seeding (22.2% vs 10.1%, p
      < 0.001) were more frequent in the IDC group; however, SAPS II scores were lower
      in the IDC group (27 vs 37, p < 0.001). ICU admission rates in the two groups
      were similar. The isolate tested susceptible to empirical therapy more frequently
      in the IDC group (88.9% vs 78.0%, p = 0.003). Seven-day (3.1 vs 16.5%), 30-day
      (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC
      group (all p < 0.001). Multivariate analysis showed that effective initial
      therapy was the only variable associated with the protective effect of IDC. In
      patients with SAB, all-cause mortality was significantly lower in patients who
      had an IDC, because of the higher proportion of patients receiving effective
      initial antibiotics.

PMID- 22382825
TI  - Recent advances in the rehabilitation of anterior cruciate ligament injuries.
AB  - Rehabilitation following anterior cruciate ligament surgery continues to change,
      with the current emphasis being on immediate weight bearing and range of motion,
      and progressive muscular strengthening, proprioception, dynamic stability, and
      neuromuscular control drills. The rehabilitation program should be based on
      scientific and clinical research and focus on specific drills and exercises
      designed to return the patient to the desired functional goals. The goal is to
      return the patient's knee to homeostasis and the patient to his or her sport or
      activity as safely as possible. Unique rehabilitation techniques and special
      considerations for the female athlete will also be discussed. The purpose of this
      article is to provide the reader with a thorough scientific basis for anterior
      cruciate ligament rehabilitation based on graft selection, patient population,
      and concomitant injuries.

PMID- 22382824
TI  - Depressive symptoms and serum lipid levels in young adult women.
AB  - Accumulating data suggest that depression is associated with risk factors for
      cardiovascular disease, but few studies have investigated potential behavioral
      mediators of such associations, particularly among women. In this study of
      healthy young adult women (n = 225), we examined associations among depressive
      symptoms, health behaviors, and serum lipid levels. Depressive symptoms were
      assessed with the 20-item Center for Epidemiologic Studies-Depression scale, and
      a fasting blood sample was obtained for serum lipid levels, including total
      cholesterol, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL
      C). Diet was measured using 24-h recalls, and other health behaviors (physical
      activity, smoking) were assessed via self-report questionnaire. Results indicated
      a modest negative association between depressive symptoms and LDL-C levels.
      Higher levels of depressive symptoms were also associated with lower total and
      insoluble dietary fiber intake, both of which were associated with HDL-C and LDL
      C. Mediational analyses indicated a significant indirect effect of depressive
      symptoms on LDL-C via total and insoluble dietary fiber in unadjusted analyses,
      but not in adjusted analyses. The present findings suggest that depressive
      symptoms are inversely associated with serum LDL-C levels in young adult women,
      but that these associations are not likely mediated by adverse lifestyle
      behaviors.

PMID- 22382826
TI  - [Frontier in the research and development of metal-based drugs].

PMID- 22382827
TI  - [Drug discovery research in in-vivo antitumor-active azolato-bridged dinuclear
      Pt(II) complexes].
AB  - Cis-diamminedichloridoplatinum(II) (cisplatin), which was first introduced as a
      clinical anticancer agent in the 1970s, is still among the most-utilized agents
      in current cancer chemotherapy. The discovery of cisplatin antitumor activity has
      catalyzed drug discovery research on antitumor platinum coordination compounds
      with improved efficacy. Some of new compounds show fewer side effects or expanded
      clinical applications. Apart from some clinical inconveniences, such as side
      effects, the high therapeutic efficacy of platinum-based agents implies that
      further modifications may lead to more effective anticancer platinum drugs which
      are effective against cancers that are typically resistant to chemotherapy, such
      as pancreatic cancer, and platinum-refractory cancer. Most of the cisplatin
      analogs cause cross-resistance to cisplatin, probably because of the similar
      biological consequences. It is suggested that platinum complexes which interact
      with DNA; the most probable target molecule, through a mechanism different from
      that of cisplatin can provide unique anticancer spectra required for next
      generation anticancer drugs. Therefore, we synthesized a series of azolato
      bridged dinuclear Pt(II) complexes with a general formula, [{cis
      Pt(NH(3))(2)}(2)(u-OH)(u-azolato)](2+), which can form 1,2-intrastrand crosslinks
      with a minimal DNA distortion, whereas clinical platinum-based drugs provide 1,2
      intrastrand crosslink with severe DNA distortion. Indeed, they exhibit much
      higher in vitro cytotoxicity than cisplatin, and we have recently found one of
      the dinuclear Pt(II) complexes exhibits markedly high in vivo antitumor efficacy
      against pancreatic cancer. Here, I update our drug-discovery research on the
      series of azolato-bridged dinuclear Pt(II) complexes that may be more effective
      and safer than current anticancer chemotherapeutic agents.

PMID- 22382828
TI  - [Possible use of zinc ions for anti-pigmentation and anti-wrinkling skin care].
AB  - Active studies of skin science have gradually clarified the underlying mechanisms
      of skin problems regarding skin beauty. The major skin problems are the
      alterations in appearance such as the hyperpigmentation and wrinkling caused by
      age. Those skin alterations are accelerated by solar light, particularly by
      ultraviolet rays, and it has been reported that reactive oxygen species (ROS)
      also involves in most of those processes. Thus, the reduction of oxidative stress
      induced by intracellular ROS is one approach to prevent and improve
      hyperpigmentation and wrinkling. Zn(2+) is well-known as an inducer of MT
      (metallothionein) and gammaGCS (gamma-glutamyl cysteinyl synthetase: a rate
      limiting enzyme of glutathione synthesis) via the up-regulation of their mRNAs
      through a metal transcription factor. The inductions of both MT and glutathione
      are expected to reduce oxidative stress due to the more effective scavenging of
      intracellular ROS. Several complexes of Zn(2+) and amino acids were synthesized
      and then evaluated for effects on MT synthesis in HaCaT keratinocytes. Among the
      complexes tested, we found a superior induction by a Zn(2+) glycine complex,
      Zn(Gly)(2). The anti-pigmentation and anti-wrinkling effects of Zn(Gly)(2) are
      introduced in this paper.

PMID- 22382829
TI  - [Development of polaprezinc research].
AB  - Zinc, one of essential trace elements, functions as a structural component in
      more than 300 different enzymes in the human body, playing crucial roles in
      performing a number of functions, including protein and DNA synthesis. Also
      hereditary or dietary zinc deficiency leading to pathological changes such as
      growth retardation, skin symptoms and taste disorders in human has been well
      investigated. Polaprezinc (Promac((r)), Zeria Pharmaceutical Co., Ltd.), a
      chelate compound consisting of zinc and L-carnosine, is a zinc-related medicine
      approved for the first time in Japan, which has been clinically used to treat
      gastric ulcers. Its mechanism of action is believed to oxygen radical scavenging,
      anti-oxidation, and acceleration of wound healing. Further, as zinc deficiency is
      known to be a primary cause of taste disorders, a clinical phase III study is in
      progress to determine taste disorders as a new indication of polaprezinc. The
      pharmacological action of polaprezinc, however, on taste disorders remains
      unclear. So we examined the effect of polaprezinc on taste disorders induced by
      feeding rats a zinc-deficient diet and clarified its mechanism of action in
      restoring the reduced zinc content in the lingual epithelium and improving
      delayed cell proliferation of taste bud cells due to zinc deficiency. In this
      review, we primarily make reference to our own data on the pharmacological action
      of polaprezinc on taste disorders and introduce recent research on the effects of
      polaprezinc in treating other diseases.

PMID- 22382830
TI  - [Benefit of vanadium compound in therapy for cardiovascular diseases].
AB  - There is an increase in cardiovascular disease and cardiovascular risk after
      menopause. Development of animal models of cardiovascular disease in
      postmenopause is critical to define pathophysiological mechanism underlying
      cardiovascular injury and to advance in the therapy. We first developed a rat
      model of postmenopausal cardiac myocardial hypertrophy and dysfunction. Rats were
      surgically ovariectomized (OVX) and subjected to pressure overload (PO) by aortic
      banding. We found marked reduction of protein kinase B (Akt) activity and
      endothelial nitric oxide synthase (eNOS) phosphorylation. Since we found bis(1
      oxy-2-pyridinethiolato) oxovanadium (IV) (VO(OPT)), as strong stimulator of Akt
      in vivo, we treated it for OVX-PO hypertrophy model. Interestingly, VO(OPT)
      treatment significantly attenuated cardiac hypertrophy and prevented the progress
      from hypertrophy to heart failure. The cardioprotective effects of VO(OPT) were
      closely associated with increases in Akt activity and eNOS phosphorylation in the
      left ventricule. The cardiac hypertrophy and contractile dysfunction were
      significantly improved by VO(OPT) treatment. Taken together vanadium compound are
      possible therapeutics for cardiac hypertrophy and heart failure following
      hypertension in postmenopausal women.

PMID- 22382831
TI  - [Copper compounds ameliorate cardiovasclur dysfunction and diabetes in animals].
AB  - Copper (Cu) is essential for our daily life and it is found at approximately 110
      mg in human adults with the body weight of 70 kg, in which this metal occurs at
      46 mg in the bone and 26 mg in the muscle. Although Cu exists in the brain
      (approximately 5 mg/kg), liver (6 mg/kg), kidney (13 mg/kg), erythrocytes (90
      mg/L), bile (6 mg/L) and serum (120 mg/L), its organ-specific distribution is not
      yet known. In metalloenzymes such as oxidoreductases, Cu is abundantly found and
      greatly contributes in life functions. In addition, intracellular Cu transport
      system has been revealed in connection with iron (Fe) and zinc (Zn) intracellular
      transport systems. In spite of such great contribution of Cu in life, no Cu
      containing pharmaceutics have yet been known. Under such background, the author
      and his research group have tried to examine a possibility of Cu compounds as
      potential pharmaceutics. In the review, the following topics are concerned; (1)
      improvement of cardiovascular dysfunction in animals by di-nuclear Cu-asprinate
      complex on the basis of the results on its reactive oxygen scavenging (ROS)
      effect, (2) blood glucose-lowering effect of mono-nuclear Cu-picolinate complex
      in streptozotocin (STZ)-induced type 1-like diabetic animals, based on the
      results on in vitro insulinomimetic activity, and (3) anti-diabetic effect of
      copper sulfate in animals with regard to the inhibition of alpha-glucosidase
      activity. These results suggest that copper ion and its complexes are possible
      seeds for developing Cu-containing pharmaceutics in the future.

PMID- 22382832
TI  - [New developments in pharmaceutical research to support a secure and safe
      society].

PMID- 22382833
TI  - [Relation analysis between intracellular distribution of nanomateriarls, ROS
      generation and DNA damage].
AB  - With recent development of nanotechnology, nanomaterials (NMs) have been
      developed with innovative function and expected to cause a paradigm shift in
      various industry such as cosmetics, medicine and food. NMs begin to establish
      firm position in Japan as base of various industrials, in fact, a part of them
      have been already applied to various products. On the other hand, it is suggested
      that these innovative properties may induce unknown biological responses. It is
      concerned about the effect of these innovative properties to human health. Based
      on these situations, to evaluate risk of NMs, it is started to collect
      information about safety of NMs (Nano Safety Science). With this in mind, we
      analyzed the relationship between particle size and the in vitro effect of
      amorphous nanosilica (nSP) using human keratinocyte cells (HaCaT). Our results
      indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level
      of reactive oxygen species (ROS), leading to DNA damage. On the other hand, a
      markedly reduced response was observed using submicron-sized silica particles.
      Next, we investigate relationship between endocytosis, generation of ROS and DNA
      damage using endocytosis inhibitor, cytochalasin D (CytoD). As result, CytoD 
      treatment reduced nSP70-mediated ROS generation and DNA damage. This suggested
      that endocytosis is involved in nSP70-mediated cellular effects. Thus, particle
      size affects amorphous silica-induced ROS generation and DNA damage in HaCaT
      cells. We believe that clarification of the endocytosis pathway of nSP will
      provide useful information for hazard identification as well as the design of
      safer forms of nSP.

PMID- 22382834
TI  - [Effects of intestinal flora on the expression of cytochrome P450 3A in the
      liver].
AB  - Living organisms eliminate foreign low-antigenic substances, such as drugs and
      environmental pollutants, by detoxification mediated by metabolizing cytochrome
      P450 (CYP). We have examined the possible regulation of CYP expression by enteric
      bacteria. Cyp mRNA expression levels, Cyp3a protein expression level, and the
      activity of Cyp3a in hepatic microsomal fractions were compared in germ-free (GF)
      and specific pathogen-free (SPF) mice. We evaluated hepatic Cyp3a11 mRNA
      expression levels and Cyp3a metabolic activity in GF and SPF mice after five days
      of antibiotic administration. The fecal levels of lithocholic acid (LCA)
      producing bacteria and hepatic taurolithocholic acid (TLCA) were also measured.
      Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of
      Cyp3a in SPF mice were higher than those in GF mice, indicating that enteric
      bacteria increases hepatic Cyp3a expression. The effects of enteric bacteria
      reducing antibiotics on Cyp3a expression were examined. We observed that
      decreasing enteric bacteria with antibiotics in SPF mice caused a significant
      decrease in the hepatic Cyp3a11 mRNA expression, TLCA, and fecal LCA-producing
      bacteria compared to the group that did not receive antibiotics. No change in
      Cyp3a11 expression was observed in GF mice that were treated with antibiotics.
      Administration of LCA to GF mice showed an increase in Cyp3a11 expression similar
      to that of SPF mice. The enzymes of the enteric bacteria are believed to
      metabolize and detoxify drugs by either reduction or hydrolysis. The results of
      this study indicate that changes in enteric bacteria may alter the expression and
      activity of hepatic drug metabolizing enzymes and pharmacokinetics. Therefore,
      enteric bacteria should be closely monitored to ensure the safe use of drugs.

PMID- 22382835
TI  - [Involvement of microRNA in the induction of drug-metabolizing enzymes].
AB  - MicroRNAs (miRNAs) are small noncoding RNAs of about 20 nucleotides in length and
      participate in the post-transcriptional regulation of gene expression.
      Accumulating evidence indicates that miRNA binds to 3'-UTR of its target mRNAs
      and thereby destabilizes the transcripts or suppresses the translation. It is
      expected that miRNAs could have diverse functions and therefore play a role in
      the gene expression caused by the drug treatment, which have yet to be
      determined. Demonstration of the participation of specific miRNA in the drug
      mediated gene expression would make it a biomarker for the toxicological
      assessment and help an understanding of molecular machinery of the drug-drug
      interaction. Under these backgrounds, we investigated the change of miRNAs in the
      liver of mice treated with phenobarbital, a typical inducer for drug-metabolizing
      enzymes, and demonstrate the participation of miRNAs in the phenobarbital
      regulated gene expression. We investigated the relationship between phenobarbital
      mediated changes in miRNA and mRNA by using Agilent miRNA microarray and DNA
      microarray, followed by real time RT-PCR. From these experiments, it was
      suggested that the phenobarbital-induced changes in cyp2c29 and mrp3 are
      regulated by miR-30a and miR-29b, respectively. In addition, we obtained evidence
      that indicates a phenobarbital-mediated decrease in miR-122, a highly abundant
      liver-specific miRNA, leads to the activation of the transcription factor CAR and
      thereby induces drug-metabolizing enzymes.

PMID- 22382836
TI  - [Safety and skin penetration of nanoparticles].
AB  - Human beings are exposed or otherwise a subjected to a various chemical
      compounds. Various nanomaterials are contained in the chemical compounds which
      are used in many fields. Nanomaterials are also used in cosmetics: titanium
      dioxide and zinc oxide are examples. Consumers who apply cosmetics to their skin
      as well as workers at industrial plants may thus be exposed to these
      nanoparticles. Therefore, it is of great importance to evaluate the safety of
      these nanoparticles. In this review, we describe the possibility of nanoparticle
      penetration to skin following exposure, which makes it urgent to evaluate the
      safety factors. In general, it is necessary to take account of the desquamation
      rate of the stratum corneum and the permeation pathway and size of nanoparticles
      when considering such penetration. One layer of the human stratum corneum is
      peeled off per day. Therefore, a chemical compound of which the skin penetration
      is lower than the desquamation rate does not permeate through the skin, when the
      compound infiltrates the stratum corneum. Hence, compounds with a molecular
      weight of more than 500 Daltons do not permeate through the stratum corneum.
      However, we must also pay attention to the appendage routes, although the
      aforementioned layer is the primary permeation route of nanoparticles. The
      contribution of appendage routes must be taken into consideration.

PMID- 22382837
TI  - [How do transport and metabolism affect the biological effects of polycyclic
      aromatic hydrocarbons?].
AB  - Polycyclic aromatic hydrocarbons (PAHs), some of which are
      carcinogenic/mutagenic, are generated by combustion of fossil fuels and also
      released through tanker or oilfield accident to cause a large scale environmental
      pollution. PAHs concentration in China is especially high in East Asia because of
      many kinds of generation sources such as coal heating systems, vehicles and
      factories without exhaust gas/particulate treatment systems. So, the atmospheric
      pollution caused by PAHs in China has been seriously concerned from the view
      point of health effects. Like yellow sand and sulfur oxide, PAHs exhausted in
      China are also transported to Japan. Additionally, strongly mutagenic nitrated
      PAHs (NPAHs), estrogenic/antiestrogenic PAH hydroxides (PAHOHs) and reactive
      oxygen species-producing PAH quinones (PAHQs) are formed from PAHs by the
      chemical reaction during the transport. Furthermore these PAHOHs and PAHQs are
      produced by the metabolism in animal body. In the biological activities caused by
      the above PAH derivatives, the structure-activity relationship was observed. In
      this review, our recent results on the generation of PAH derivatives by
      atmospheric transport and metabolism are reported. Also, the existing condition
      of PAHs as atmospheric pollutants is considered.

PMID- 22382838
TI  - [Safety assessment of nanomaterials in reproductive developmental field].
AB  - A diverse array of nanomaterials (NMs) such as amorphous nanosilica and carbon
      nanotubes have become widespread in use due to the development of nanotechnology.
      NMs are already being applied in universal fields because they have unique
      physicochemical properties. On the other hand, the increasing use of NMs has
      raised public concern about their potential risks to human health. In particular,
      recent reports indicated that carbon nanotubes induced mesothelioma-like lesions
      in mice, in a way similar to those induced by crocidolite asbestos. However,
      current knowledge of the potential risk of nanomaterials is considered
      insufficient. Because NMs have the potential to improve the quality of human
      life, it is essential to ensure the safety of NMs and provide information for
      designing NMs with safety. Especially, few studies have examined the effect of
      NMs on maintenance of pregnancy. Similar to the cases of thalidomide, a lot of
      evidence shows that fetuses are affected more than adults by a variety of
      environmental toxins because of physiological immaturity. Therefore it is
      essential to examine the effect of NMs on fetuses and pregnancies. Here we
      introduce the potential risk of amorphous nanosilica, most widely used NMs in
      food and the cosmetics field, to induce fetotoxicity and useful information for
      developing NMs with safety.

PMID- 22382839
TI  - [Collaborative development of an advanced practical education program to train
      pharmacists in leadership].

PMID- 22382840
TI  - [Implementation of the program of "Collaborative Development of Advanced
      Practical Education to Train Pharmacists in Leadership" under the joint operation
      of the pharmaceutical departments in fourteen national universities].
AB  - "Collaborative Development of Advanced Practical Education Program to Train
      Pharmacists with Leadership" applied jointly by the pharmaceutical departments of
      fourteen national universities was selected to receive the special expenditure
      support of Ministry of Education, Culture, Sports, Science and Technology for
      fiscal year 2010 under "the Training of Highly Skillful Professionals and
      Improvement of the Quality of the Function of Professional Education". This
      project is to promote the collaborative development of the educational program
      which will make it possible to further advance and substantiate the education of
      pharmacists in the six year course of the pharmaceutical department for the
      ultimate purpose to introduce pharmacists with leadership who can play an active
      role and fill in a leadership position in a wide range of responsibilities into
      the society which, more and more, has come to expect pharmacy to take the
      initiative in acting against health hazards caused by infections, foods and
      environmental pollution as well as to meet the diversification of healthcare. To
      be more specific, this project is to try and evaluate the following programs
      repeatedly based on the plan-do-check-act (PDCA) cycle: 1) Practical medical and
      pharmaceutical education program; 2) Program concerning research on long term
      themes and advanced education; 3) Program concerning training and education of
      SPs (standardized patients or simulated patients) and PBL (problem-based
      learning) tutorial education; and 4) Program concerning the method of evaluation
      of education. Through this repeated trial and evaluation, this project ultimately
      seeks to construct a highly effective practical educational program which
      integrates each university's achievements and educational attempts rich in
      originality.

PMID- 22382841
TI  - [Development of advanced pharmacy practice experience in national universities].
AB  - The six-year pharmacy program started in April 2006 in Japan. In the new program,
      students in the fifth year of the pharmacy course undergo a long-term practice
      experience (pharmacy clerkship) in community pharmacy and hospital pharmacy
      settings as compulsory 20 course credits. The new pharmacy practice experience
      started in May 2010. A start of the new system was a chance as for beginning
      movement, thus we conducted the questionnaire survey for the following steps. The
      finding obtained from our questionnaires indicated that many universities had
      already planned to execute new approaches, such as an advanced practice at
      outpatient units, an with medical students, and so on.

PMID- 22382842
TI  - [Development of advanced educational programs, including research programs, for
      undergraduate students in National Universities: the facts in 2010].
AB  - This article summarizes detailed facts obtained from the questionnaire conducted
      in 2010 at about 14 National Universities on the topic of "Research programs and
      advanced educational programs for undergraduate students". The contents of the
      questionnaire included: (1) Research programs based on the coalition of
      university and hospital and/or community pharmacy, other Graduate Schools, such
      as School of Medicine etc., and the University Hospital, (2) Educational systems
      for the achievement of research programs and their research outcomes, (3)
      Research programs based on pharmacist practices, (4) Ongoing advanced educational
      programs for undergraduate students, taking advantage of the coalition with
      Graduate School, School of Medicine (and Dentistry), and University Hospital.
      Some of the advanced educational programs outlined in this questionnaire will be
      carried out by our group in the coming years and the educational benefits
      together with associated problems shall as well be clarified. This approach will
      be informative for the development of the leader-oriented pharmacist programs for
      the college of Pharmacy.

PMID- 22382843
TI  - [Current state of training in pharmacy education using a problem-based
      learning/tutorial model with simulated patients and standardized patients at
      National University Corporation].
AB  - Simulated/standardized patient-based (SP) education and problem-based learning
      (PBL) tutorial education become a powerful tool to heighten the pharmacy
      students' will to learn in order to cultivate the responsibility to contribute to
      public health and welfare as a clinical professional and to facilitate students'
      competences to solve problems by themselves. What this program is trying to do
      is: 1) to establish the system to train, educate and supply SP who are effective
      in the training and education of pharmacy students in close cooperation with the
      medical schools and their affiliated hospitals; 2) to improve the quality of the
      current PBL tutorial education and thereby establish it as an advanced education
      program in the education of senior students. We carried out the questionnaire to
      National University Corporation which establishes a school of pharmacy, as to the
      training and education of SP. The analysis of the answers to the questionnaire
      revealed the present status of SP in the Pharmaceutical Objective Structured
      Clinical Examination (OSCE) in the Pharmaceutical Common Achievement Test, and
      the existence of the problems on how to standardize SP as well as how to cover
      such expenses. Furthermore, the activity of the first year consisted of the
      exchange and sharing of information regarding the existing method of training and
      education of SP and PBL tutorial education and the identification of the problems
      to be solved in order to improve the quality of the educational program.

PMID- 22382844
TI  - [Development of evaluation methods for student performance in National
      Universities: formative assessment and portfolio].
AB  - Formative assessment which refers to frequent, interactive assessments of student
      progress and understanding is one of the most effective strategies for promoting
      high student performance and developing students' "learning to learn" skills.
      Portfolio (personal record of learning) is a useful tool for tracking individual
      student progress toward learning goals. We conducted the questionnaire survey in
      14 National Universities on approach to the formative assessment methods and the
      use of portfolio in the long-term practice experience (pharmacy clerkship) at
      community pharmacy and hospital pharmacy which was undergone for the first time
      in 2010. The finding obtained from our questionnaires implicated that portfolio
      is useful for sharing information among student, tutorial pharmacist and faculty
      members. All universities have provided tools for visible assessment of student
      achievement. However, they are not used enough for feedback on student
      performance, and formative assessment is not practiced systematically. A reason
      seems to be differences in understanding of it. In addition to improvement of the
      tools to support formative assessment, promotion of effective assessment practice
      will need for systematic evaluation.

PMID- 22382845
TI  - [Establishment of a practical training program in smoking cessation for use by
      pharmacists using cognitive-behavioral therapy and the motivational interview
      method].
AB  - We established a practical training program to nurture pharmacists who can give
      smoking cessation instructions. The program was provided to 85 interns (45 males
      and 40 females) in Teikyo University Hospital. The one-day practical training was
      provided to groups comprised of five members each. The training consisted of
      studies on the adverse effects of smoking, general outlines of the outpatient
      smoking cessation service, experiencing Smokerlyzer, studies about smoking
      cessation drugs, studies about a smoking cessation therapy using cognitive
      behavioral therapy and motivational interviewing, and case studies applying role
      playing. Before and after the practical training, we conducted a questionnaire
      survey consisting of The Kano Test for Social Nicotine Dependence (KTSND) and the
      assessment of the smoking status, changes in attitudes to smoking, and
      willingness and confidence to give smoking cessation instructions. The overall
      KTSND score significantly dropped from 14.1+/-4.8 before the training to 8.9+/
      4.8 after the training. The confidence to give smoking cessation instructions
      significantly increased from 3.4+/-1.9 to 6.2+/-1.3. Regarding the correlation
      between the smoking status and willingness and confidence to give smoking
      cessation instructions, the willingness and confidence were lower among the group
      of interns who either smoked or had smoked previously, suggesting that smoking
      had an adverse effect. A total of 88.2% of the interns answered that their
      attitudes to smoking had "changed slightly" or "changed" as a result of the
      training, indicating changes in their attitudes to smoking. Given the above, we
      believe that our newly-established smoking cessation instruction training is a
      useful educational tool.

PMID- 22382846
TI  - [Training of pharmacists in the assessment of vital signs using human subjects
      for the purpose of better pharmacist-patient communication].
AB  - Since 2005, the Japanese pharmacy education program has changed to a six year
      system from a four year-system with the aim to help students obtain a higher
      level of clinical knowledge and skill regarding humanity and morality. Under the
      new pharmacy education system, the correct assessment of vital signs is observed
      in pharmacy practice so that pharmacists can sell "over the counter drugs (OTC)"
      safely. From this point of view, we started a pharmacy practice that recognizes a
      series of vital signs, i.e., blood pulse, blood pressure, respiratory sound, and
      electrocardiogram, using a physical figure subjecting to 4th-year students
      (n=142) . After the practice, a questionnaire was conducted in order to assess
      the satisfaction of the practice. The results suggested that students could
      successfully learn physical assessment by using physical figures (ratios more
      than grade 4: 60%). Students could also evaluate the necessity of physical
      assessment (ratios more than grade 4: 70%), suggesting the practice of using
      physical figures was accepted by most students.

PMID- 22382847
TI  - [Pilot study of dementia medication compliance conducted among pharmacists
      providing home visits which evaluates the degree of drug compliance, as defined
      by numerous attributes, between patients at home and patients in a medical
      facility].
AB  - A survey was conducted among pharmacists providing "home-visit guidance on drug
      management" to patients taking medication for dementia. Factors related to
      medication adherence among patients and pharmacists' acquisition of patient
      information were then verified. The survey items were: (1) patient attributes
      (degree of care received, bed-ridden, family composition, and living
      environment); (2) the person controlling medications; (3) drug storage method and
      location; (4) dispensing method; (5) patient management of visiting nurses; (6)
      patient management of visiting physician; (7) details of pharmacist's home-visit
      guidance; (8) medication adherence; (9) five items related to cognitive function
      (short-term memory, autonomous judgment, fluctuations in level of consciousness,
      excitation and loss of orientation, understanding); and (10) ten items related of
      ADL (mobility in bed, transferring, mobility within the home or outdoors,
      dressing upper/lower body, eating, toilet use, individual hygiene, bathing). The
      t test was used to verify the number of items of patient information concerning
      cognitive function and physical function that pharmacists could acquire at a
      visit. It was suggested that pharmacists were able to acquire more patient
      information (1cognitive function and 2ADL) when they visited patients cared for
      at home, compared to facility residents (1p=0.008, 2 p=0.006). Thus, it was
      suggested that there is a latent risk concerning the pharmacist's ability to
      discover problems with administration of medications among facility residents.
      These findings demonstrate that it is essential for pharmacists to be more
      proactive about providing home-visit guidance.

PMID- 22382848
TI  - Update on the biology and treatment of lymphedema.
AB  - OPINION STATEMENT: The past decade has produced an explosion of insights into
      lymphatic vascular development and structural biology and, in parallel, into the
      function of the lymphatics in health and in disease. In lymphedema, there is a
      spectrum that extends from primary (heritable) to acquired causes of disease. The
      diagnosis of lymphatic edema implicates a very specific treatment approach that
      is predicated upon the favorable impact of physiotherapy upon lymph flow and
      protein clearance from the edematous zones of the body. The recognition of the
      unique biology that accompanies lymphatic causes of edema has stimulated new
      research directions that are likely to translate into exciting new pharmacologic
      and molecular approaches to diagnosis and treatment.

PMID- 22382849
TI  - Excision of an enlarging vaginal epidermal inclusion cyst during pregnancy:  a
      case report.
AB  - OBJECTIVE: The study aimed to report the case of a patient with an enlarging and
      symptomatic epidermal inclusion cyst during pregnancy that required surgical
      excision. MATERIALS AND METHODS: This study was a case report of a 28-year-old
      woman (gravida 8, para 5, aborta 2) at a gestational age of 18 weeks 5 days who
      reported a tender vaginal mass that had grown larger for more than a week.
      RESULTS: An enlarging symptomatic cystic mass was surgically excised.
      Histopathologic findings of the excised mass were consistent with an epidermal
      inclusion cyst with surrounding moderate chronic inflammation and cyst rupture.
      The patient's symptoms resolved completely by her postoperative visit.
      CONCLUSIONS: Although most epithelial inclusion cysts are asymptomatic and can be
      managed expectantly, cysts that enlarge or become symptomatic should be excised
      surgically.

PMID- 22382850
TI  - Cytotoxic and antioxidant marine prenylated quinones and hydroquinones.
AB  - Covering: 1972 to 2011. This review covers the literature of prenylated quinone,
      hydroquinone and naphthoquinone marine natural products with reported cytotoxic
      and/or antioxidant properties. The structures, biological activity and, where
      applicable, the syntheses of 159 cytotoxic/antioxidant compounds, isolated from
      various marine organisms, are presented, while trends in the distribution of
      these cytotoxic metabolites, across the different marine phyla, are highlighted.
      Marine prenylated quinones, hydroquinones and naphthoquinones are of mixed
      polyketide and terpenoid biogenesis and recent biosynthetic studies of selected
      compounds are discussed.

PMID- 22382851
TI  - Accuracy of real-time vs. blinded offline diagnosis of neoplastic colorectal
      polyps using probe-based confocal laser endomicroscopy: a pilot study.
AB  - BACKGROUND AND STUDY AIMS: Probe-based confocal laser endomicroscopy (pCLE) is a
      new imaging modality that enables histological examination of gastrointestinal
      mucosa during endoscopic procedures. Most studies have evaluated offline
      interpretation of pCLE images. In clinical practice, real-time interpretation is
      necessary to assist decision-making during the procedure. The aim of this pilot
      study was to compare the accuracy of real-time pCLE diagnosis made during the
      procedure with that of blinded offline interpretation to provide accuracy
      estimates that will aid the planning of future studies. PATIENTS AND METHODS:
      pCLE was performed in patients undergoing screening and surveillance colonoscopy.
      Once a polyp had been identified, one endoscopist analyzed pCLE images during the
      procedure and made a provisional "real-time" diagnosis. Saved video recordings
      were de-identified, randomized, and reviewed "offline" 1 month later by the same
      endoscopist, who was blinded to the original diagnoses. RESULTS: Images from a
      total of 154 polyps were recorded (80 neoplastic, 74 non-neoplastic). The overall
      accuracy of real-time pCLE diagnosis (accuracy 79%, sensitivity 81%, specificity
      76%) and offline pCLE diagnosis (83%, 88%, and 77%, respectively) for all 154
      polyps were similar. Among polyps < 10 mm in size, the accuracy of real-time
      interpretation was significantly lower (accuracy 78%, sensitivity 71%,
      specificity 83%) than that of offline pCLE interpretation (81%, 86%, 78%,
      respectively). For polyps >= 10 mm, the accuracy of pCLE diagnosis in real-time
      was better (accuracy 85%, sensitivity 90%, specificity 75%) than offline pCLE
      diagnosis (81%, 97%, and 50%, respectively). CONCLUSIONS: These results suggest
      that real-time and offline interpretations of pCLE images are moderately
      accurate. Real-time interpretation is slightly less accurate than offline
      diagnosis, but overall both are comparable. Additionally, there was contrasting
      accuracy between the two methods for small and large polyps.

PMID- 22382852
TI  - Endoscopic ultrasound-guided transmural drainage of infected pancreatic fluid
      collections with placement of covered self-expanding metal stents: a case series.
AB  - Endoscopic ultrasound-guided transmural drainage (EUS-GTD) has become the
      standard procedure for treating symptomatic pancreatic fluid collections. The aim
      of this series was to evaluate the efficacy and safety of covered self-expanding
      metal stent (CSEMS) placement for treating infected pancreatic fluid collections.
      From January 2007 to May 2010, 22 patients (18 M/4F; mean age 56.9) with infected
      pancreatic fluid collections (mean size, 13.2 cm) at two Italian centers were
      evaluated for EUS-GTD. In 20 of the 22 patients, EUS-GTD with CSEMS placement was
      indicated. Early complications occurred in two patients: one patient developed a
      superinfection, which was managed conservatively, and one experienced stent
      migration and superinfection, and was managed surgically. The CSEMSs were removed
      without difficulty in 18 patients after a median of 26 days, while stent removal
      failed in one patient due to inflammatory tissue ingrowth; instead it was removed
      during surgery performed for renal cancer. Clinical success was achieved without
      additional intervention in 17 patients during a mean follow-up of 610 days; only
      one symptomatic recurrence was observed. In our experience, EUS-GTD with CSEMS
      placement appears safe for the treatment of infected pancreatic fluid
      collections.

PMID- 22382853
TI  - Chronic pain and discomfort after inguinal hernia repair.
AB  - PURPOSE: The purpose of this study was to estimate the incidence and degree of
      persistent chronic pain after inguinal hernia repair performed in our hospitals.
      METHODS: We mailed a questionnaire on the frequency and intensity of
      postoperative inguinal pain and discomfort to 219 adult patients who had
      undergone inguinal hernia repair in one of our hospitals more than 3 months
      previously. RESULTS: There were 191 (87.2%) respondents, 28 (14.7%) of whom
      reported pain and 33 (17.3%) reported discomfort. The frequency of pain was
      "rare" in more than half of the patients who reported pain. No patient reported
      "continuous" pain. The intensity of the pain was "mild" in most of the patients,
      and none reported "pain that required a painkiller". The answers on the face
      scale questionnaire (score "0" to "10") were "0" or "1" for most of the patients.
      The incidence of chronic pain and/or discomfort was significantly higher in women
      than in men, and tended to be higher in patients who had undergone repair using
      onlay mesh. CONCLUSIONS: The frequency and intensity of persistent chronic pain
      or discomfort after inguinal hernia repair was not high or severe. These data
      will be useful for further studies to determine the best treatment for adult
      inguinal hernia.

PMID- 22382854
TI  - Pyogenic vertebral osteomyelitis in a breast cancer patient: report of a case.
AB  - We herein report a rare case of pyogenic vertebral osteomyelitis (PVO) coexisting
      with breast carcinoma. A 71-year-old female presented with neck pain without
      fever. Magnetic resonance imaging (MRI) showed suspected metastatic lesions in
      her neck (C7 and Th1). Fluorine-18 fluorodeoxyglucose positron emission
      tomography (FDG-PET) showed increased FDG uptake in the neck spines and in the
      left breast. A core needle biopsy of the left breast revealed the presence of
      invasive ductal carcinoma. Our first tentative diagnosis of the patient was left
      breast carcinoma with bone metastases, and first-line endocrine therapy was
      started. However, surgical intervention for the spines had to be considered,
      because her neurological symptoms progressed. A repeated MRI scan showed a
      narrowing of the disc space and fluid accumulation around the vertebrae. This
      suggested the presence of PVO rather than metastases. Surgery confirmed the
      presence of PVO in C7 and Th1, and a culture of the abscess yielded Escherichia
      coli. The patient's neurological symptoms dramatically improved after surgery.
      Breast conserving surgery was performed 3 months after the surgery for PVO. The
      patient is well and has no clinical evidence of disease 18 months after the
      breast conserving surgery. PVO is rare, but should be included in the
      differential diagnosis in patients presenting with early breast carcinoma.

PMID- 22382855
TI  - Determination of endocrine-disrupting phenols in water samples by a new manual
      shaking-enhanced, ultrasound-assisted emulsification microextraction method.
AB  - Manual shaking-enhanced, ultrasound-assisted emulsification microextraction (MS
      USAEME) combined with ultraperformance liquid chromatography (UPLC) with UV
      detection has been developed for the determination of five endocrine-disrupting
      phenols (EDPs) in seawater samples and detergent samples: 4-tert-butylphenol (4-t
      BP), 4-cumylphenol (4-CP), 4-tert-octylphenol (4-t-OP), 2,4-di-tert-butylphenol
      (2,4-di-t-BP) and 4-nonylphenol (4-NP). Optimum conditions were found to be: 25
      MUL 1-bromohexadecane as extraction solvent, 5 mL of aqueous sample and 1 g of
      NaCl to control the ionic strength; manual shaking for 10 s; ultrasonication for
      1 min; centrifugation for 3 min at 5000 rpm (speed). For MS-USAEME, manual
      shaking for 10 s is essential for effective extraction when the ultrasonic
      extraction time is as brief as 1 min. The small volume of aqueous sample enhances
      the effect of manual shaking significantly. For seawater samples, the limit of
      detection (LOD) was 0.5-2.8 ng mL(-1), the limit of quantification (LOQ) was 1.8
      9.3 ng mL(-1) with the relative standard deviation (RSD) in the range 4.2-10.3%.
      For detergent samples, the LOD was 0.4-2.4 ng mL(-1), LOQ was 1.6-8.2 ng mL(-1)
      and RSD 4.7-10.0%. The relative recovery was 96-109% for seawater samples and 81
      106% for the detergent samples.

PMID- 22382856
TI  - Identification and quantification of six major alpha-dicarbonyl process
      contaminants in high-fructose corn syrup.
AB  - High-fructose corn syrup (HFCS) is a widely used liquid sweetener produced from
      corn starch by hydrolysis and partial isomerization of glucose to fructose.
      During these processing steps, sugars can be considerably degraded, leading, for
      example, to the formation of reactive alpha-dicarbonyl compounds (alpha-DCs). The
      present study performed targeted screening to identify the major alpha-DCs in
      HFCS. For this purpose, alpha-DCs were selectively converted with o
      phenylendiamine to the corresponding quinoxaline derivatives, which were analyzed
      by liquid chromatography with hyphenated diode array-tandem mass spectrometry (LC
      DAD-MS/MS) detection. 3-Deoxy-D-erythro-hexos-2-ulose (3-deoxyglucosone), D-lyxo
      hexos-2-ulose (glucosone), 3-deoxy-D-threo-hexos-2-ulose (3-deoxygalactosone), 1
      deoxy-D-erythro-hexos-2,3-diulose (1-deoxyglucosone), 3,4-dideoxyglucosone-3-ene,
      methylglyoxal, and glyoxal were identified by enhanced mass spectra as well as
      MS/MS product ion spectra using the synthesized standards as reference. Addition
      of diethylene triamine pentaacetic acid and adjustment of the derivatization
      conditions ensured complete derivatization without de novo formation for all
      identified alpha-DCs in HFCS matrix except for glyoxal. Subsequently, a ultra
      high performance LC-DAD-MS/MS method was established to quantify 3
      deoxyglucosone, glucosone, 3-deoxygalactosone, 1-deoxyglucosone, 3,4
      dideoxyglucosone-3-ene, and methylglyoxal in HFCS. Depending on the alpha-DC
      compound and concentration, the recovery ranged between 89.2% and 105.8% with a
      relative standard deviation between 1.9% and 6.5%. Subsequently, the alpha-DC
      profiles of 14 commercial HFCS samples were recorded. 3-Deoxyglucosone was
      identified as the major alpha-DC with concentrations up to 730 MUg/mL HFCS. The
      total alpha-DC content ranged from 293 MUg/mL to 1,130 MUg/mL HFCS. Significantly
      different alpha-DC levels were not detected between different HFCS
      specifications, but between samples of various manufacturers indicating that the
      alpha-DC load is influenced by the production procedures.

PMID- 22382857
TI  - Fast detection of triacetone triperoxide (TATP) from headspace using planar solid
      phase microextraction (PSPME) coupled to an IMS detector.
AB  - Triacetone triperoxide (TATP) is a high explosive synthesized from easily
      available reactants making it accessible for illicit uses. In this study, fast
      detection of TATP is achieved using a novel planar solid-phase microextraction
      (PSPME) as a preconcentration and sampling device for headspace analysis offering
      improved sensitivity and reduced sampling time over the conventional fiber-based
      solid-phase microextraction (SPME) when followed by ion mobility spectrometer
      (IMS) detection. Quantitation and comparison of the retention capabilities of
      PSPME as compared to the commercially available SPME were determined using TATP
      standards and analyzed using gas chromatography-mass spectrometry for SPME
      analysis and a commercial IMS with no instrumental modification for PSPME. Static
      and dynamic headspace extractions were used and compared for PSPME extractions,
      in which low milligram quantities of TATP were detected within 30 s of static
      mode sampling and less than 5 s in the dynamic mode sampling for PSPME-IMS.

PMID- 22382858
TI  - The lost art of intubation: assessing opportunities for residents to perform
      neonatal intubation.
AB  - OBJECTIVE: The objective of this study is to assess the opportunities afforded to
      and competence of pediatric residents in performing neonatal endotracheal
      intubations. STUDY DESIGN: The records of all intubations performed on neonates
      over a 3-year period at a university-based birthing hospital were reviewed to
      assess the relationships between outcomes, types of providers and the setting of
      intubations. RESULT: A total of 785 attempts were made during 362 intubations.
      Pediatric residents were given the opportunity to intubate 38% of the cohort
      (n=137) and were successful on 21% of the attempts. Residents were more likely to
      perform intubation in the neonatal intensive care unit (vs delivery room;
      P<0.001), in non-emergency situations (P<0.001), and on older (P<0.001) and
      larger (P=0.07) infants. CONCLUSION: Opportunities for residents to intubate
      neonates were few and their success rate was low. In the current care paradigm,
      it is doubtful if trainees can be sufficiently skilled in endotracheal intubation
      during residency. Residents that plan to pursue procedure-intensive
      subspecialties may benefit from other models for training.

PMID- 22382859
TI  - Thermal protection of the newborn in resource-limited environments.
AB  - Appropriate thermal protection of the newborn prevents hypothermia and its
      associated burden of morbidity and mortality. Yet, current global birth practices
      tend to not adequately address this challenge. Here, we discuss the
      pathophysiology of hypothermia in the newborn, its prevention and therapeutic
      options with particular attention to resource-limited environments. Newborns are
      equipped with sophisticated mechanisms of body temperature regulation. Neonatal
      thermoregulation is a critical function for newborn survival, regulated in the
      hypothalamus and mediated by endocrine pathways. Hypothermia activates cellular
      metabolism through shivering and non-shivering thermogenesis. In newborns,
      optimal temperature ranges are narrow and thermoregulatory mechanisms easily
      overwhelmed, particularly in premature and low-birth weight infants. Hyperthermia
      most commonly is associated with dehydration and potentially sepsis. The lack of
      thermal protection promptly leads to hypothermia, which is associated with
      detrimental metabolic and other pathophysiological processes. Simple thermal
      protection strategies are feasible at community and institutional levels in
      resource-limited environments. Appropriate interventions include skin-to-skin
      care, breastfeeding and protective clothing or devices. Due to poor provider
      training and limited awareness of the problem, appropriate thermal care of the
      newborn is often neglected in many settings. Education and appropriate devices
      might foster improved hypothermia management through mothers, birth attendants
      and health care workers. Integration of relatively simple thermal protection
      interventions into existing mother and child health programs can effectively
      prevent newborn hypothermia even in resource-limited environments.

PMID- 22382860
TI  - Does a highest pre-ductal O(2) saturation <85% predict non-survival for
      congenital diaphragmatic hernia?
AB  - OBJECTIVE: To analyze operative repair, extracorporeal membrane oxygenation
      (ECMO) and survival rates based on highest pre-ductal oxygen saturation (Pre
      O(2)SAT) in a large infant cohort reported to Congenital Diaphragmatic Hernia
      Study Group Registry between 2000 and 2010. STUDY DESIGN: Analyzed data included
      gestational age, birth weight, defect side and size, repair, ECMO use, survival
      and highest reported PaO(2) and Pre-O(2)SAT in first 24 h of life. We excluded
      614 infants due to severe anomaly. Pre-O(2)SAT data were available for 1672
      infants. RESULT: Among infants with highest Pre-O(2)SAT value <85%, survival
      (24/105=23%) and repair (55/105=52%) rates were significantly decreased compared
      with infants with higher values. Survival increased to 44% for infants with
      highest Pre-O(2)SAT<85% who underwent operative repair. Of these, 83% (20/24)
      required ECMO support compared with 15% (144/961) of survivors with Pre
      O(2)SAT>99% (P<0.001). The lowest reported Pre-O(2)SAT with survival was 32% and
      for survival without ECMO was 52%. CONCLUSION: A reported highest Pre-O(2)SAT<85%
      in the first 24 h of life was not uniformly fatal; but survival of infants with
      Pre-O(2)SAT<85% was associated with high ECMO use and prolonged hospitalization.

PMID- 22382861
TI  - Investigation of the extracts from Bidens pilosa Linn. var. radiata Sch. Bip. for
      antioxidant activities and cytotoxicity against human tumor cells.
AB  - The aim of this study was to evaluate antioxidant activities and cytotoxicity
      against human tumor cell lines of extracts from Bidens pilosa Linn. var. radiata
      Sch. Bip. (BP). Total phenolic and flavonoid contents of the extracts were
      determined by ultraviolet spectrophotometry. Furthermore, the antioxidant
      properties of different polarity fractions extracted from BP were evaluated using
      DPPH and ABTS radical scavenging test and FRAP assay. The ethyl acetate fraction
      (EE-BP) showed the highest antioxidant activity compared to other fractions. In
      addition, the anti-proliferative activities of the extracts on four human tumor
      cells, namely MCF-7, HepG2, MGC 803 and RKO, were investigated by MTT method. The
      EE-BP displayed the most remarkable anti-proliferative effect against the tumor
      cells, particularly RKO cell in dose- and time-dependent manner. The antioxidant
      activities and cytotoxicity correlated highly with the total phenolic and
      flavonoid contents, respectively. Furthermore, The active ingredient BP-6, namely
      5,7,4'-trihydroxy-3,3'-dimethyl-flavonol, was isolated and purified with the
      purity above 99.00% and content of 0.15% in EE-BP detected by HPLC, which could
      significantly inhibit the proliferation of RKO cells with the IC(50) value of
      6.66 MUmol/l. In order to characterize the apoptotic RKO cells, flow cytometry
      and DNA fragmentation assay were performed. Apoptotic cell numbers increased in a
      dose-dependent manner after the treatment with different concentrations of EE-BP
      and BP-6 for 12 and 6 h, respectively. DNA ladders in apoptotic RKO cells could
      be easily visualized when exposed to 200 MUg/ml of the EE-BP for 36 h. Taken
      together, our work indicated that BP had potentially therapeutic value against
      colorectal cancer.

PMID- 22382862
TI  - Anti-angiogenic effect of alpha-mangostin.
AB  - Eleven known prenyl xanthones, isolated from the pericarp of Garcinia mangostana,
      were tested for their ability to inhibit the phosphorylation of kinase domain
      receptor (KDR) tyrosine kinase. alpha-Mangostin was found to inhibit
      phosphorylation of KDR. alpha-Mangostin also showed to inhibit phosphorylation of
      the Y1175 residue of KDR (10 MUM). This is the first report that alpha-mangostin
      inhibited the phosphorylation of KDR tyrosine kinase and also the Y1175 residue
      of KDR. alpha-Mangostin also showed inhibitory effects on proliferation of human
      umbilical vein endothelial cells (HUVECs) (IC(50) 1.2 MUM) and human umbilical
      artery endothelial cells (IC(50) 2.4 MUM), as well as the migration (IC(50) 0.034
      MUM) and tubule formation (at the concentrations of 0.6 and 1.2 MUM) of HUVECs.
      These results suggest that the inhibition of the phosphorylation of KDR tyrosine
      kinase is concerned in the anti-angiogenic activity of alpha-mangostin.

PMID- 22382863
TI  - Development of HPLC fingerprint for species differentiation and quality
      assessment of Rhizoma Smilacis Glabrae.
AB  - Rhizoma Smilacis Glabrae (RSG) is a commonly used herbal material in functional
      food and Traditional Chinese Medicine. A HPLC chromatographic fingerprint was
      developed for its quality control and species differentiation. Nine peaks were
      found in the chromatogram of RSG and all these peaks were identified by diode
      array detection and electrospray ionization-MS/MS: 5-O-caffeoylshikimic acid,
      taxifolin, engeletin, isoengeletin, trans-resveratrol, astilbin and its three
      stereoisomers. Six of these constituents were consistently found in 18 batches of
      samples. The standard fingerprint of RSG was generated by mean simulation of all
      tested samples. Using the standard fingerprint, RSG could be easily
      differentiated from Rhizoma Smilacis Chinae and Rhizoma Heterosmilacis, the two
      species that can be confused with RSG.

PMID- 22382864
TI  - Qualitative studies enrich telemonitoring research, practice, and  technology
      design.

PMID- 22382865
TI  - Dawning of a new lung age?

PMID- 22382866
TI  - Enhanced recovery from respiratory  infection following treatment with a PDE-5 
      inhibitor: a single case study.

PMID- 22382867
TI  - Predictors of 25-hydroxyvitamin D and its association with risk factors for
      prostate cancer: evidence from the prostate testing for cancer and treatment
      study.
AB  - PURPOSE: Circulating 25-hydroxyvitamin D (25(OH)D) may protect against prostate
      and other cancers. Few epidemiology studies have measured 25(OH)D on all
      participants, weakening the evidence-base through reduced statistical power and
      the potential for bias. We developed a score to predict individual 25(OH)D based
      on potential predictors, including sun exposure, nutrient intake, and vitamin D
      pathway genes, providing a method of substituting missing values. We assessed the
      usefulness of predicted 25(OH)D by comparison with multiple imputation of 25(OH)D
      levels. METHODS: Amongst 1,091 controls from a population-based case-control
      study (ProtecT), we quantified relationships of sun exposure, demographic,
      clinical, anthropologic, nutrient, and genetic data with circulating 25(OH)D and
      constructed several prediction scores from subsets of these measures. We
      investigated associations of three prostate cancer risk factors (PSA level, BMI,
      family history of prostate cancer) with 25(OH)D levels in sensitivity analyses
      based upon participants with measured 25(OH)D only and based upon the addition of
      all participants with missing 25(OH)D levels substituted by prediction score
      values or by multiple imputation. RESULTS: Our score accounted for 27.7% of the
      variation in measured 25(OH)D. Associations with risk factors of prostate cancer
      were consistent across the different estimates of 25(OH)D. However, standard
      deviations for the prediction score did not incorporate extra error from
      prediction. Multiple imputation of missing 25(OH)D values predicted a more
      realistic range of 25(OH)D. CONCLUSION: In epidemiological studies of cancer risk
      associated with vitamin D, multiple imputation of missing 25(OH)D is preferable
      to prediction scores, as a wider range of 25(OH)D levels are imputed and
      appropriate confidence intervals calculated.

PMID- 22382868
TI  - Factors associated with diagnostic and treatment intervals for prostate cancer in
      Queensland, Australia: a large cohort study.
AB  - OBJECTIVE: To examine the relation between socio-demographic and clinical
      factors, and time from consultation to diagnosis and treatment for men with
      prostate cancer. METHODS: Men diagnosed with prostate cancer (n = 1,064, response
      rate = 82%) were recruited through participating urologists and hospital
      outpatient clinics in Queensland, Australia, and completed telephone interviews
      and self-administered questionnaires. Outcome measures were the diagnostic
      interval (initial consultation to definitive diagnosis) and treatment interval
      (definitive diagnosis to start of treatment). RESULTS: Median time to diagnosis
      was 73 days (IQR = 41-144) and median treatment interval was 65 days (IQR = 36
      107). After adjustment, men were more likely to wait more than 70 days for their
      definitive diagnosis when they initially presented with symptoms (compared with a
      general checkup) or did not have private health insurance. For treatment
      interval, men without private health insurance or who were treated with
      radiotherapy alone were more likely to wait more than 70 days. Treatment
      intervals were shorter when men received androgen deprivation therapy combined
      with radiotherapy. CONCLUSIONS: Differences in waiting times for diagnosis and
      treatment related to access to private hospital care suggest that there are
      inequities in health-care service provision that are system based.

PMID- 22382869
TI  - Enhancement of the electrochemical capacitance of TiO2 nanotube arrays through
      controlled phase transformation of anatase to rutile.
AB  - Here, we report the fabrication of self-organized titania (TiO(2)) nanotube array
      supercapacitor electrodes through controlled phase transformation of TiO(2), with
      aerial capacitances as high as 2.6 mF cm(-2), which far exceeds the values so far
      reported in the literature. The role of phase transformation in the
      electrochemical charge-discharge behaviour of nanocrystalline TiO(2) nanotubes is
      investigated and discussed in detail. The ease of synthesis and the exceptional
      electrochemical properties make these nanotube arrays an alternative candidate
      for use in energy storage devices.

PMID- 22382870
TI  - Surgical anatomy of the human middle ear: an insight into cochlear implant
      surgery.
AB  - PURPOSE: This research was designed to aid practical otologic studies of the
      human middle ear. The topographic anatomy access of the middle ear was described
      with special focus to the cochlear implant procedure. It was conducted in an
      attempt to elucidate factors that would ultimately determine the ease of
      insertion of an electrode array. METHODS: Fifteen right and 12 left temporal
      bones were dissected under the surgical microscope. After performing appropriate
      incisions, the distances between the stapedius muscle tendon, incus long crus and
      the cochleostomy were measured with the help of a digital microscope (Dino-Lite
      plus((r))). RESULTS: After performing statistical analysis, we found that strong
      relationship exists in the distances between the measured anatomical landmarks.
      CONCLUSION: Microscopic anatomical studies of the temporal bone are essential to
      safely perform surgical intervention within the middle ear. The results shows
      that morphometric data concerning different anatomical structures inside the
      middle ear, particularly distances, is an important contribution towards the
      planning of safe surgical procedures.

PMID- 22382872
TI  - Pleiotrophin expression during odontogenesis.
AB  - Pleiotrophin (PTN) is an extracellular matrix-associated growth factor and
      chemokine expressed in mesodermal and ectodermal cells. It plays an important
      role in osteoblast recruitment and differentiation. There is limited information
      currently available about PTN expression during odontoblast differentiation and
      tooth formation, and thus the authors aimed to establish the spatiotemporal
      expression pattern of PTN during mouse odontogenesis. Immortalized mouse dental
      pulp (MD10-D3, MD10-A11) and odontoblast-like (M06-G3) and ameloblast-like (EOE
      3M) cell lines were grown and samples prepared for immunocytochemistry, Western
      blot, and conventional and quantitative PCR analysis. Effects of BMP2, BMP4, and
      BMP7 treatment on PTN expression in odontoblast-like M06-G3 cells were tested by
      quantitative PCR. Finally, immunohistochemistry of sectioned mice mandibles and
      maxillaries at developmental stages E16, E18, P1, P6, P10, and P28 was performed.
      The experiments showed that PTN, at both the mRNA and protein level, was
      expressed in all tested epithelial and mesenchymal dental cell lines and that the
      level of PTN mRNA was influenced differentially by the bone morphogenetic
      proteins. The authors observed initial expression of PTN in the inner enamel
      epithelium with prolonged expression in the ameloblasts and odontoblasts
      throughout their stages of maturation and strong expression in the terminally
      differentiated and enamel matrix-secreting ameloblasts and odontoblasts of the
      adult mouse incisors and molars.

PMID- 22382873
TI  - Exploring channeling optimized radiofrequency energy: a review of radiofrequency
      history and applications in esthetic fields.
AB  - INTRODUCTION: Because of its high efficiency and safety, radiofrequency (RF)
      energy is widely used in the dermatological field for heating biological tissue
      in various esthetic applications, including skin tightening, skin lifting, body
      contouring, and cellulite reduction. This paper reviews the literature on the use
      of nonablative RF energy in the esthetic field and its scientific background. The
      purpose of this article is to describe in detail the extensive use of medical
      devices based on RF technology, the development of these medical devices over the
      years, and recent developments and trends in RF technology. METHODS: The authors
      conducted a systematic search of publications that address safety and efficacy
      issues, technical system specifications, and clinical techniques. Finally, the
      authors focused on their own clinical experiences with the use of patented
      Channeling Optimized RF Energy technique and mechanical massage. An in-vivo study
      was conducted in domestic pigs, with a thermal video camera. Twenty-seven female
      patients participated in a cellulite and body shaping study. The treatments were
      conducted according to a three-phase protocol. An additional 16 females
      participated in a skin tightening case study. All of the patients underwent three
      treatment sessions at 3-week intervals, each according to a protocol specific to
      the area being treated. RESULTS: The review of the literature on RF-based systems
      revealed that these systems are safe, with low risks for potential side effects,
      and effective for cellulite, body contouring, and skin tightening procedures. The
      in-vivo measurements confirmed the theory that the penetration depth of RF is an
      inverse function of its frequency, and using a vacuum mechanism makes an
      additional contribution to the RF energy penetration. The heating effect of RF
      was also found to increase blood circulation and to induce collagen remodeling.
      The results from the cellulite and body shaping treatments showed an overall
      average improvement of 55% in the appearance of cellulite, with an average
      circumferential reduction of 3.31 cm in the buttocks, 2.94 cm in the thighs, and
      2.14 cm in the abdomen. The results from the skin tightening procedure showed
      moderate improvement of skin appearance in 50% and significant improvement in
      31%. At the follow-up visits the results were found to be sustained without any
      significant side effects. CONCLUSION: Of all tissue heating techniques, RF-based
      technologies appear to be the most established and clinically proven. The design
      and specifications of the described vacuumassisted bipolar RF device fall within
      the range of the specifications currently prescribed for esthetic, nonablative RF
      systems.

PMID- 22382874
TI  - Contribution of endermology to improving indurations and panniculitis/lipoatrophy
      at glatiramer acetate injection site.
AB  - INTRODUCTION: Endermology is a mechanical massage therapy that enables fat
      mobilization and body contouring. The authors' aim was to assess the effect of
      endermology on indurations and panniculitis/lipoatrophy associated with
      subcutaneous administration of glatiramer acetate in patients with multiple
      sclerosis (MS). METHODS: This was a multicenter pilot experience carried out in
      patients with MS treated with glatiramer acetate who showed indurations and/ or
      panniculitis/lipoatrophy at the injection site. Patients underwent endermology
      and glatiramer acetate treatment according to clinical practice. The primary
      endpoint was the change in indurations and/or panniculitis/lipoatrophy after 12
      endermology sessions. RESULTS: Between April and July 2011, a total of 13
      evaluable patients were included (mean age, 40.7+/-3.1 years; female, 100%;
      white, 100%; mean MS duration, 10.1+/-2.3 years; previous MS treatment, 46.2%;
      mean glatiramer acetate treatment duration, 27.3+/-9.5 months). Eleven patients
      (84.6%) showed local indurations (mean diameter, 3.4+/-0.5 cm; mean number, 9.0+/
      1.0) and six patients (46.2%) areas of panniculitis/ lipoatrophy (mean number,
      5.0+/-1.1). After 12 endermology sessions, patients with indurations reported
      having experienced a reduction in size (10 patients [90.9%]; mean diameter, 0.1+/
      0.05 cm; P<0.001) and number of indurations (nine patients [81.8%]; mean number,
      2.3+/-1.1; P<0.005). These indurations completely disappeared from arms, thighs,
      buttocks, and abdomen in six (75.0%), six (75.0%), two (50.0%), and three (42.9%)
      patients, respectively. Three of these patients (27.3%) recovered from all
      indurations. Although panniculitis/lipoatrophy did not completely disappear, all
      patients reported improvements. Most patients with indurations (63.6%) felt very
      satisfied and considered endermology very useful for reducing indurations. All
      patients with panniculitis/lipoatrophy were satisfied and considered to be
      endermology useful in improving it. In addition, endermology enabled glatiramer
      acetate tolerance to be improved in most patients (60.0%). CONCLUSION:
      Endermology may contribute to improving indurations and panniculitis/ lipoatrophy
      at the site of subcutaneous injection of glatiramer acetate in patients with MS,
      enabling areas of injection to recover, and treatment tolerance to increase.

PMID- 22382875
TI  - Infrared LED irradiation applied during high-intensity treadmill training
      improves maximal exercise tolerance in postmenopausal women: a 6-month
      longitudinal study.
AB  - Reduced aerobic fitness is associated with an increased risk of cardiovascular
      diseases among the older population. The aim of this study was to investigate the
      effects of LED irradiation (850 nm) applied during treadmill training on the
      maximal exercise tolerance in postmenopausal women. At the beginning of the
      study, 45 postmenopausal women were assigned randomly to three groups, and 30
      women completed the entire 6 months of the study. The groups were: (1) the LED
      group (treadmill training associated with phototherapy, n = 10), (2) the exercise
      group (treadmill training, n = 10), and (3) the sedentary group (neither physical
      training nor phototherapy, n = 10). The training was performed for 45 min twice a
      week for 6 months at intensities between 85% and 90% maximal heart rate (HRmax).
      The irradiation parameters were 39 mW/cm(2), 45 min and 108 J/cm(2). The
      cardiovascular parameters were measured at baseline and after 6 months. As
      expected, no significant differences were found in the sedentary group (p >=
      0.05). The maximal time of tolerance (Tlim), metabolic equivalents (METs) and
      Bruce stage reached significantly higher values in the LED group and the exercise
      group (p < 0.01). Furthermore, the HR, double product and Borg score at isotime
      were significantly lower in the LED group and in the exercise group (p < 0.05).
      However, the time of recovery showed a significant decrease only in the LED group
      (p = 0.003). Moreover, the differences between before and after training (delta
      values) for the Tlim, METs and HR at isotime were greater in the LED group than
      in the exercise group with a significant intergroup difference (p < 0.05).
      Therefore, the infrared LED irradiation during treadmill training can improve
      maximal performance and post-exercise recovery in postmenopausal women.

PMID- 22382877
TI  - Rare duplication or deletion of exons 6, 7 and 8 in CYBB leading to X-linked
      chronic granulomatous disease in two patients from different families.
AB  - Chronic granulomatous disease (CGD) is a rare congenital disorder in which
      phagocytes cannot generate superoxide (O(2)(-)) and other microbicidal oxidants
      due to mutations in one of the five components of the O(2)(-)-generating NADPH
      oxidase complex. The most common form is caused by mutations in CYBB on the X
      chromosome, encoding gp91phox, the enzymatic subunit of the phagocyte NADPH
      oxidase. Here, we report two rare cases of male X-linked CGD patients, one caused
      by a 5.7-kb duplication of a region containing CYBB exons 6 to 8 and the other
      caused by a deletion of this same region. We found both the duplication in
      patient 1 and the deletion in patient 2 to be bordered by a GT repeat. Indeed, in
      control DNA, the 3' part of CYBB intron 5 contains a GT repeat and the 5' part of
      intron 8 also contains such a repeat. Duplication of exons 6, 7 and 8 in patient
      1 was probably caused by a non-homologous crossing over between the two GT
      repeats. The deletion found in patient 2 probably arose from a similar
      misalignment. The results found in these patients were confirmed by multiplex
      ligation-dependent probe amplification. The clinical profile of XCGD is severe in
      both patients.

PMID- 22382876
TI  - Induction of IgM, IgA and IgE antibodies in colorectal cancer patients vaccinated
      with a recombinant CEA protein.
AB  - PURPOSE: Previous clinical studies have indicated that natural IgM antibodies
      have the ability to induce apoptosis of tumor cells but IgE and IgA may also
      mediate tumor cell killing (in addition to IgG). The aim of the study was to
      analyse induction of IgM, IgA and IgE antibodies in patients vaccinated with the
      tumor associated antigen CEA. METHODS: Twenty-four resected CRC patients without
      macroscopic disease were immunized seven times with CEA +/- GM-CSF. Four
      different dose schedules were used over a 12-month period. IgM, IgA and IgE
      antibody responses against recombinant CEA were determined by ELISA. Patients
      were monitored immunologically for 36 months and clinically for 147 months.
      RESULTS: GM-CSF significantly augmented the anti-CEA response for all three
      antibody classes. Low dose of CEA tended to induce a higher IgM, IgA or IgE anti
      CEA antibody response than higher. Anti-CEA IgA antibodies could lyse CEA
      positive tumor cells in antibody dependent cellular cytotoxicity (ADCC) as well
      as in complement dependent cytotoxicity (CDC). A significant correlation between
      survival and high IgA anti-CEA titers was noted (p = 0.02) irrespective of GM-CSF
      treatment. CONCLUSIONS: The observation that IgA anti-CEA antibodies were
      cytotoxic and associated with improved survival might indicate that also these
      antibodies may exert a clinical anti-tumor effect.

PMID- 22382878
TI  - Persistence of a large population of exhausted monoclonal B cells in mixed
      cryoglobuliemia after the eradication of hepatitis C virus infection.
AB  - PURPOSE: Functionally exhausted and mostly autoreactive B-cells with a peculiar
      CD21(low)CD11c(+) phenotype accumulate in several human immunological disorders
      including common variable immunodeficiency, HIV infection and rheumatoid
      arthritis. In HCV-associated mixed cryoglobulinemia (MC) there is accumulation of
      exhausted clonal B cells expressing a V(H)1-69-encoded cross-reactive idiotype;
      these cells are phenotypically heterogeneous, displaying either a
      CD21(low)CD11c(+) or a marginal zone (MZ)-like (IgM(+)CD27(+)CD21(+)CD11c(-))
      phenotype. Irrespective of their phenotype, V(H)1-69(+) B-cells are unresponsive
      to the stimulation of Toll-like receptor 9 (TLR9). We investigated the fate of
      these cells after the eradication of HCV. METHODS: Fourteen MC patients were
      studied before and after antiviral therapy. V(H)1-69(+) B-cells were identified
      using the G6 monoclonal antibody and their phenotype and responsiveness to the
      stimulation of TLR9 were investigated. RESULTS: In seven virological non
      responders, cryoglobulin levels and the number and phenotype of V(H)1-69(+) B
      cells remained substantially unchanged. By contrast, in sustained viral
      responders cryoglobulinemia subsided and the number of V(H)1-69(+) B cells
      declined. However, high proportions of MZ-like V(H)1-69(+) B cells retaining
      unresponsiveness to TLR9 stimulation persisted for several months in these
      patients. CONCLUSIONS: Clonal expansion of CD21(low) V(H)1-69(+) B cells may
      depend on continual stimulation by HCV, whereas their MZ-like counterparts may
      persist for years after the eradication of infection. Prolonged survival of
      exhausted MZ-like B cells after withdrawal of the initial inciting stimulus may
      contribute to the accumulation of autoreactive B cells in immunological
      disorders.

PMID- 22382879
TI  - An open-label, phase 1 study evaluating safety, tolerability, and
      pharmacokinetics of linifanib (ABT-869) in Japanese patients with solid tumors.
AB  - PURPOSE: This phase 1 study assessed the safety, tolerability, pharmacokinetics,
      and preliminary antitumor activity of linifanib in Japanese patients with
      advanced solid tumors. METHODS: Patients were assigned to one of four sequential
      cohorts (0.05, 0.10, 0.20, or 0.25 mg/kg) of oral, once-daily linifanib on a 21
      day cycle. Adverse events (AEs) were assessed per common terminology criteria for
      adverse events v3.0; tumor responses were assessed by response evaluation
      criteria in solid tumors. RESULTS: Eighteen patients were enrolled. Eleven (61%)
      received >=3 prior therapies. Dose-limiting toxicities were Grade 3 ALT increase
      (0.10 mg/kg linifanib) and Grade 1 T-wave inversion (0.25 mg/kg linifanib)
      requiring dose interruption for >7 days and discontinuation on day 29. The most
      common linifanib-related AE was hypertension. Other significant treatment-related
      AEs included proteinuria, fatigue, and palmar-plantar erythrodysaesthesia.
      Linifanib pharmacokinetics were dose-proportional across 0.10-0.25 mg/kg. Two
      patients (11.1%) had confirmed partial responses, 12 had a best response of
      stable disease (11 had stable disease for >=12 weeks), and four patients were not
      evaluable due to incomplete data. Four patients (lung cancer, breast cancer,
      thymic cancer, sarcoma) have continued linifanib for >=48 weeks (range, 48-96+
      weeks). CONCLUSION: Linifanib was well tolerated with promising preliminary
      clinical activity in Japanese patients. Later-phase global studies examining
      linifanib efficacy will include Japanese patients.

PMID- 22382880
TI  - Decitabine triphosphate levels in peripheral blood mononuclear cells from
      patients receiving prolonged low-dose decitabine administration: a pilot study.
AB  - PURPOSE: Decitabine is a nucleoside analog used in the treatment for
      myelodysplastic syndrome. The compound requires intracellular conversion to its
      triphosphate to become active. Decitabine triphosphate has, however, never been
      quantified in peripheral blood mononuclear cells (PBMCs) from patients. METHOD:
      This article describes a method for the quantitative determination of decitabine
      triphosphate in PBMCs using liquid chromatography coupled to tandem mass
      spectrometry. The method was applied to ex vivo incubated whole blood samples and
      samples from three patients receiving prolonged low-dose decitabine treatment.
      RESULTS: We successfully quantitated decitabine triphosphate in PBMCs.
      Considerable levels were detected in PBMCs from two patients that responded well
      to therapy, whereas only low levels were present in a non-responding patient.
      Moreover, the data show that, in contrast to plasma decitabine, intracellular
      decitabine triphosphate accumulates during a treatment cycle of nine infusions at
      a dose of 15 mg/m(2). CONCLUSIONS: The results suggest a relationship between
      decitabine triphosphate levels and response to therapy. Based on the observed
      accumulation of decitabine triphosphate during a treatment cycle, a less
      intensive dose scheme could be feasible.

PMID- 22382882
TI  - Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for
      esophageal cancer.
AB  - PURPOSE: We aimed to evaluate the safety, tolerability, and efficacy of
      combination preoperative chemoradiotherapy as first-line treatment in patients
      with advanced esophageal cancer. METHODS: We performed a phase I dose-escalation
      trial of docetaxel at 25-40 mg/m(2) in four planned dose levels in 3-6 patient
      cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70
      mg/m(2) on days 1 and 29) and 5-fluorouracil (70 mg/m(2)/day on days 1-4 and 29
      32) and concurrent radiation therapy (40 Gy). The tumors were resected during
      weeks 10-13. RESULTS: This study included 7 patients with esophageal cancer. The
      dose-limiting toxicity was observed at a biweekly docetaxel dose of 30 mg/m(2)
      when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia,
      and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25 mg/m(2).
      Grade 3/4 hematological toxicity was observed in 71% of the patients and grade
      3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86%
      (complete, 57% and partial, 29%). All patients underwent surgery, and there were
      no deaths as a result of postoperative complications. CONCLUSIONS: This
      preoperative chemoradiotherapy regimen using triplets is feasible but results in
      moderate toxicity. It is noteworthy that this regimen was associated with a high
      rate of pathological complete remission.

PMID- 22382883
TI  - Phase I dose-escalation study of vinflunine hard capsules administered twice a
      day for 2 consecutive days every week in patients with advanced/metastatic solid
      tumors.
AB  - BACKGROUND: Vinflunine is a new microtubule inhibitor of the vinca-alkaloid
      family. It is marketed in transitional cell carcinoma of urothelial tract as a 20
      min infusion given every 3 weeks in Europe. METHODS: In this phase I study,
      vinflunine was administered to patients with advanced malignancies as hard
      capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial
      blood samples were collected during the first cycle for pharmacokinetic
      investigations. RESULTS: Thirty-six patients (pts) were treated at 6 dose levels
      150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts)
      and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300
      mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile
      neutropenia with diarrhea). The lower dose level of 270 mg/day was the
      recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia,
      fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy
      of the flat-fixed dosing regimen, as no correlation between clearance of
      vinflunine and body surface area was evidenced. Blood concentrations and exposure
      increased with dose, and a pharmacokinetic accumulation was observed, which is
      consistent with the terminal half-life of the compounds. The inter-individual
      exposure variability at the RD was 35%. CONCLUSION: Repeated weekly
      administration of oral vinflunine is feasible and exhibits a moderate inter
      individual PK variability. The MTD was achieved at 300 mg/day given for 2
      consecutive days. According to the protocol rules, the RD was established at 270
      mg/day.

PMID- 22382881
TI  - TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination
      therapy efficacy: optimization of dosing regimens and schedules.
AB  - PURPOSE: Subregional hypoxia is a common feature of tumors and is recognized as a
      limiting factor for the success of radiotherapy and chemotherapy. TH-302, a
      hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors,
      delivers a cytotoxic warhead to the tumor, while maintaining relatively low
      systemic toxicity. The antitumor activity, different dosing sequences, and dosing
      regimens of TH-302 in combination with commonly used conventional
      chemotherapeutics were investigated in human tumor xenograft models. METHODS:
      Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan,
      doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH
      302 in eleven human xenograft models, including non-small cell lung cancer
      (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic
      cancer. RESULTS: The antitumor activity of docetaxel, cisplatin, pemetrexed,
      irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when
      combined with TH-302 in nine out of eleven models tested. Administration of TH
      302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus
      other sequences tested. Simultaneous administration of TH-302 and
      chemotherapeutics increased toxicity versus schedules with dosing separations. In
      a dosing optimization study, TH-302 administered daily at 50 mg/kg
      intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal
      response with minimal toxicity. CONCLUSIONS: TH-302 enhances the activity of a
      wide range of conventional anti-neoplastic agents in a broad panel of in vivo
      xenograft models. These data highlight in vivo effects of schedule and order of
      drug administration in regimen efficacy and toxicity and have relevance to the
      design of human regimens incorporating TH-302.

PMID- 22382884
TI  - Defining innovations of therapeutic interventions: a position paper by the
      Italian Society of Hospital Pharmacists.
AB  - Defining innovation in pharmacotherapy is complex because general definitions
      cannot be easily adapted to the specificity of different therapeutic areas. The
      Italian Society of Hospital Pharmacists has developed a position paper in which
      three criteria are used to recognise innovation to a new intervention: (1)
      clinical relevance of the trial's primary end-point; (2) evidence of superiority;
      (3) use of an adequate comparator in the controlled trial. Clinically relevant
      end-points should appear in predetermined lists by therapeutic area managed by
      our society; likewise, the third criterion must be documented by an authoritative
      therapeutic guideline recognised to be still valid. A preliminary attempt is
      presented to retrospectively apply these criteria, particularly the first one, to
      a series of 21 clinical trials; this initial experience has generated a first
      list of clinically relevant end-points. This approach of innovation assessment is
      proposed for application also in the field of medical devices.

PMID- 22382885
TI  - European Society of Clinical Pharmacy (ESCP) glossary of scientific terms: a tool
      for standardizing scientific jargon.
AB  - INTRODUCTION: This glossary is a tool for clinicians who have to confront topics
      in which medical, scientific and technical jargon is closely linked. It provides
      definitions for the key concepts and terms of pharmaceutical care, clinical
      pharmacy, and research in the health care system in clinical settings. It
      includes items that are not particularly technical, but that should be part of
      the know-how of staff working in medical and scientific fields. In fact, the
      glossary can also help clinical technicians who want to understand the precise
      definition of scientific terms, which often do not coincide with the ones used in
      the practice setting. PRINCIPAL GOALS AND OBJECTIVES: The aim of this glossary is
      to aid in the development of more standardized and established terminology for
      clinical pharmacy, facilitate communication among different stakeholders and,
      ultimately, contribute to a higher-quality health care system. RESULTS: The
      glossary contains 165 definitions of concepts and principles in clinical
      pharmacy, and terms widely used in this field. The criteria for the inclusion of
      terms were specific applications in health promotion, or terms used in other
      fields that have a specific meaning or application when used in reference to
      clinical activity. CONCLUSIONS: The glossary arose from the need to standardize
      terminology in the scientific field. It was not intended as a comprehensive
      listing that would include all medical terms, but as a useful tool for clinical
      pharmacists working in this area, and for users who occasionally encounter
      unusual, often hard to understand, terminology.

PMID- 22382886
TI  - Impact of the pharmacist on a multidisciplinary team in an antimicrobial
      stewardship program: a quasi-experimental study.
AB  - BACKGROUND: Antimicrobial stewardship programs (ASP) have been implemented to
      promote rational use of antimicrobial drugs. Multidisciplinary teams are needed
      to form effective committees. OBJECTIVE: Assess the impact of ASP, with and
      without the presence of a pharmacist, in a cardiology hospital in Brazil.
      METHODS: The program started with an infectious disease (ID) physician, and after
      22 months, a pharmacist started to work in the ASP team. We present data related
      to: stage 1-before the program implementation; stage 2-with the ID physician; and
      stage 3 with the inclusion of a pharmacist. Analysis was made by segmented
      regression of time series. RESULTS: After the start of ASP there was a
      significant reduction of consumption of all antimicrobials. The pharmacist
      contributed to the significant reduction in consumption of fluoroquinolones,
      clindamycin and ampicillin/sulbactam and in increase in total cephalosporins use
      in stage 3. Adherence rate to the ASP team recommendations was 64.1%. There was a
      significant reduction of 69% in hospital antibiotics costs. CONCLUSION: A non
      expensive ASP in a limited resource country resulted in reductions in
      antimicrobial consumption and costs. The multidisciplinary team contributed to
      maximize the impact of interventions.

PMID- 22382887
TI  - Views of the Scottish general public on community pharmacy weight management
      services: international implications.
AB  - BACKGROUND: Obesity has reached pandemic levels, with more than 1.5 billion
      adults being affected worldwide. In Scotland two-thirds of men and more than half
      of women are either overweight or obese, placing Scotland overall third behind
      the United States of America and Mexico. All community pharmacies in Scotland are
      contracted to provide public health services such as smoking cessation and there
      is increasing interest in their contribution to weight management. Researching
      this area in Scotland may provide valuable information to facilitate the
      development of community pharmacy services in other parts of the UK and
      internationally. OBJECTIVES: To describe the views of the Scottish general public
      on the provision of weight management services via community pharmacies. SETTING:
      General public in Scotland. METHODS: A cross-sectional postal questionnaire
      survey of 6,000 randomly selected members of the Scottish general public aged 18
      years and over. MAIN OUTCOME MEASURES: Views on community pharmacy led weight
      management services. RESULTS: Questionnaires were returned by 20.6% (n = 1,236).
      Over half 60.1% (n = 751) agreed or strongly agreed that they had easy access to
      pharmacy services in general and around one-third agreed (35%; n = 438) that it
      was more convenient to obtain weight management advice from a pharmacist than it
      is to make an appointment with a GP. Most respondents however lacked awareness of
      the types of health services available through community pharmacy (13.2%; n =
      162) and would not feel comfortable speaking to a pharmacist or medicines counter
      assistant about weight related issues (25%; n = 320). Concerns over privacy
      (47.3%; n = 592) and perceived lack of pharmacists' specialist knowledge (open
      comments) were identified as potential barriers to service uptake by the general
      public. CONCLUSION: Overall, respondents appear to be receptive to the idea of
      accessing weight management services through community pharmacy but a perceived
      lack of privacy, poor knowledge of pharmacists' skill level and of public health
      services available to them may explain the reluctance in the uptake of such
      services to date. The general public's views expressed in this study may help to
      shape future community pharmacy led weight management service provision.

PMID- 22382888
TI  - Efficient extraction of Rh(III) from nitric acid medium using a hydrophobic ionic
      liquid.
AB  - Rhodium(III) has been successfully extracted from an aqueous nitric acid solution
      using a hydrophobic ammonium based ionic liquid and CMPO or TODGA as extractant.
      This result has significant potential for the recovery of rhodium from spent
      nuclear fuel and thereby increasing the worldwide supply of this rare metal.

PMID- 22382889
TI  - Anatomic anterior cruciate ligament reconstruction utilizing the double-bundle
      technique.
AB  - The goal of every orthopaedic surgeon should be to restore anatomy as close as
      possible to normal. Intense research on reconstruction of the anterior cruciate
      ligament (ACL) and an advancing knowledge of the anatomy and function of the 2
      primary bundles of the ACL have led to techniques of ACL reconstruction that more
      closely restore normal anatomy. Restoring the ACL footprint is one of the most
      important goals of the surgery, and the choice between anatomic single-bundle and
      double-bundle ACL reconstruction is determined by the anatomical features of each
      patient. After reconstruction, the graft undergoes a complex, lengthy process of
      remodeling; therefore, inappropriate (early), aggressive rehabilitation can lead
      to graft failure and compromise the patient's outcome. The purpose of this
      article is to provide an overview of the anatomy and function of the ACL, the
      methods for anatomic single-bundle and double-bundle ACL reconstruction, and our
      recommendations for postoperative rehabilitation.

PMID- 22382890
TI  - Near infrared thieno[3,4-b]pyrazine sensitizers for efficient quasi-solid-state
      dye-sensitized solar cells.
AB  - Three near infrared (NIR) metal-free organic sensitizers (FNE32, FNE34, FNE36)
      based on the thieno[3,4-b]pyrazine derivative have been designed and synthesized
      for application in quasi-solid-state dye-sensitized solar cells (DSSCs). These
      organic dyes demonstrate maximum absorption bands at 596-625 nm due to the
      presence of the thieno[3,4-b]pyrazine derivative, which facilitates the
      intramolecular electron transfer from the donor to the acceptor. Quasi-solid
      state DSSCs based on FNE34 display efficient photoelectric conversion over the
      whole visible range extending into the NIR region up to 900 nm with maximum
      incident monochromatic photon-to-electron conversion efficiency (IPCE) of 77%,
      yielding a short-circuit photocurrent density of 16.24 mA cm(-2) and a power
      conversion efficiency of 5.30%. To the best of our knowledge, this is the highest
      efficiency for quasi-solid-state DSSCs based on an organic NIR dye. When exposed
      to one-sun illumination for 1000 h, the quasi-solid-state DSSC based on FNE34
      exhibits good long-term stability with almost constant power conversion
      efficiency.

PMID- 22382891
TI  - Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic
      patterns in 1346 childhood and adult cases and their comparison with the reports
      from Western countries.
AB  - It has been generally acknowledged that the diagnosis, treatment and prognosis
      evaluation of leukemia largely rely on an adequate identification of genetic
      abnormalities. A systemic analysis of genetic aberrations was performed in a
      cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL)
      in China. The pediatric patients had higher incidence of hyperdiploidy and
      t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence
      of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all
      P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically
      correlated (P<0.0001). In comparison with Western cohorts, the incidence of
      t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL
      (25.24%) seemed to be much higher in our group, while the incidence of t(12;21)
      (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients.
      The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20
      38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports.
      In addition, the frequencies of HOX11L2 in adult patients were much higher in our
      cohort than in Western countries (20.69% vs 4-11%). In general, it seems that
      Chinese ALL patients bear more adverse prognostic factors than their Western
      counterparts do.

PMID- 22382892
TI  - Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have
      biased VH4-34 immunoglobulin gene expression and proliferate in a distinct
      inflammatory environment.
AB  - Ocular adnexal marginal zone B-cell lymphomas (OAMZLs) arise in the connective
      tissues of the orbit or in the mucosa-associated lymphoid tissue of the
      conjunctiva. Here, we present the immunological and genetic analyses of 20
      primary Chlamydia psittaci (Cp)-negative OAMZLs. Analysis of the immunoglobulin
      variable heavy chain (IgV(H)) gene usage demonstrated a significant preference
      for V(H)4-34. A combined analysis across all previously published OAMZLs
      confirmed that this is a general feature of OAMZL, in particular of the Cp
      negative group. Our series of OAMZLs did not express the characteristic
      rheumatoid factor V(H)DJ(H) rearrangements that were previously found in salivary
      gland- and gastric-marginal zone B-cell lymphomas (MZBCLs). We did not detect the
      MZBCL-specific chromosomal translocations, t(11;18) API2-MALT1 (mucosa-associated
      lymphoid tissue1) and t(14;18) IgH/MALT1. Two cases contained a premature stop
      codon in the A20 gene (TNFAIP3) and one case harbored the activating MYD88
      hotspot mutation L265P. Variable nuclear expression of BCL10, NFkappaB1 (p50) and
      NFkappaB2 (p52) suggests that other additional genetic abnormalities affecting
      the NFkappaB pathway exist within this group of lymphomas. OAMZL showed variable
      expression of the chemokine receptor CXCR3 and integrin alpha4beta7 by the tumor
      B cells, and low interferon-gamma and interlukin-4 mRNA levels in the tissue,
      indicative of an inflammatory environment with features in between those
      previously found in cutaneous and other extranodal MZBCL. The strongly biased
      usage of V(H)4-34 in Cp-negative OAMZLs suggests involvement of a particular
      stimulatory (auto-) antigen in their development.

PMID- 22382893
TI  - Germline copy number variation associated with Mendelian inheritance of CLL in
      two families.

PMID- 22382894
TI  - The MLL partial tandem duplication in adults aged 60 years and older with de novo
      cytogenetically normal acute myeloid leukemia.

PMID- 22382895
TI  - Clonal relationship between langerhans cell histiocytosis and myeloid sarcoma.

PMID- 22382896
TI  - A consensus method for updating psychosocial measures used in NIOSH health hazard
      evaluations.
AB  - OBJECTIVE: An expert panel was convened to select practical, valid psychosocial
      measures for use during National Institute for Occupational Safety and Health
      field investigations. METHODS: A taxonomy of psychosocial constructs was
      developed using existing taxonomies and criteria regarding the malleability,
      actionability, and validity of constructs. Panel members identified measures for
      each construct based on their expertise and experience. Measures were selected on
      the basis of the following criteria: practicality, brevity, validity,
      availability of existing data, and lack of confounds between psychosocial
      constructs and outcomes. RESULTS: The panel came to a consensus in recommending
      24 measures representing 22 constructs. CONCLUSIONS: It is important that the
      National Institute for Occupational Safety and Health regularly evaluates its
      methodologies to ensure it is in line with current best practices. The measures
      identified will be used modularly in the National Institute for Occupational
      Safety and Health fieldwork depending on the nature of the evaluation request,
      industry type, and worker population.

PMID- 22382897
TI  - Serendipitous fragment-based drug discovery: ketogenic diet metabolites and
      statins effectively inhibit several carbonic anhydrases.
AB  - Acetoacetic acid and R-3-hydroxy-butyric acid (BHB) are "ketone bodies",
      metabolites produced during the ketogenic diet. We discovered that they inhibit
      in the submicromolar-micromolar range several carbonic anhydrase (CA, EC 4.2.1.1)
      isoforms involved in relevant physiologic processes such as lipogenesis and
      tumorigenesis. The BHB fragment is also present in the molecules of most statins,
      widely used drugs for inhibiting cholesterol biosynthesis through the 3-hydroxy-3
      methyl-glutaryl-CoA reductase pathway. Three such statins, atorvastatin,
      fluvastatin and rosuvastatin, showed submicromolar-low nanomolar inhibition of
      the fifteen human isoforms hCA I-XIV. Our data point out that in addition to
      their cholesterol lowering properties, these drugs may exert a therapeutic effect
      by inhibiting lipogenesis through mitochondrial CA inhibition. The statins are
      also low nanomolar inhibitors of the tumor-associated isoforms CA IX and XII.
      Based on the BHB/statin scaffolds, antiepileptic, antiobesity and antitumor
      compounds with higher affinity for the various CA isoforms involved in
      epileptogenesis (CA VA, VB, VII), lipogenesis (CA III, CA VA, CA VB) and
      tumorigenesis (CA IX and CA XII) may be designed.

PMID- 22382898
TI  - Infrared colloidal lead chalcogenide nanocrystals: synthesis, properties, and
      photovoltaic applications.
AB  - Simple solution phase, catalyst-free synthetic approaches that offer
      monodispersed, well passivated, and non-aggregated colloidal semiconductor
      nanocrystals have presented many research opportunities not only for fundamental
      science but also for technological applications. The ability to tune the
      electrical and optical properties of semiconductor nanocrystals by manipulating
      the size and shape of the crystals during the colloidal synthesis provides
      potential benefits to a variety of applications including photovoltaic devices,
      light-emitting diodes, field effect transistors, biological imaging/labeling, and
      more. Recent advances in the synthesis and characterization of colloidal lead
      chalcogenide nanocrystals and the achievements in colloidal PbS or PbSe
      nanocrystals solar cells have demonstrated the promising application of infrared
      emitting colloidal lead chalcogenide nanocrystals in photovoltaic devices. Here,
      we review recent progress in the synthesis and optical properties of colloidal
      lead chalcogenide nanocrystals. We focus in particular upon the size- and shape
      controlled synthesis of PbS, PbSe, and PbTe nanocrystals by using different
      precursors and various stabilizing surfactants for the growth of the colloidal
      nanocrystals. We also summarize recent advancements in the field of colloidal
      nanocrystals solar cells based on colloidal PbS and PbSe nanocrystals.

PMID- 22382899
TI  - A targetable fluorescent sensor for hypochlorite based on a luminescent europium
      complex loaded carbon nanotube.
AB  - A new europium complex covalently modified single-walled carbon nanotube (SWNT)
      was reported here as an emissive nanosensor for the determination of
      hypochlorite. FT-IR, UV-vis, TEM and SEM proved that it was successfully linked
      to the SWNT surface. A luminescence quenching effect of this nanoprobe was
      rapidly observed in the presence of ClO(-). Moreover, the quenching process can
      be detected within 1 s and the detection limit could reach 9 * 10(-8) M. We
      regarded that the ligand exchange process and the high vibration energy of the
      ClO(-) resulted in this selective recognition behavior.

PMID- 22382900
TI  - Local delivery of recombinant osteoprotegerin enhances postorthodontic tooth
      stability.
AB  - Relapse after orthodontic tooth movement is a significant problem in
      orthodontics. The purpose of this study was to examine the efficacy of the
      osteoclast inhibitor osteoprotegerin-Fc (OPG-Fc) for inhibiting postorthodontic
      relapse. Rat maxillary molars were moved mesially and allowed to relapse for 24
      days. Low-dose (1 mg/kg) or high-dose (5 mg/kg) OPG-Fc or saline was injected
      adjacent to the molars during relapse. Tooth movement, micro-CT, histologic bone
      quality, and serum OPG and TRAP-5b were measured. OPG-Fc injections significantly
      diminished postorthodontic relapse from 63% (0.78/1.20 mm) of total movement in
      vehicle control rats to 31% (0.31/1.00 mm) in low-dose and 24% (0.28/1.16 mm) in
      high-dose OPG-Fc groups 24 days after appliance removal. Normalization of bone
      and periodontal tissues occurred as early as 8 and 16 days in the high- and low
      dose OPG-Fc-treated groups, respectively, while the vehicle-treated group showed
      only partial tissue recovery 24 days following tooth movement. After 24 days of
      relapse, there was complete recovery to pre-tooth-movement values for bone volume
      fraction (BVF) and tissue mineral density (TMD) in both the low- and high-dose
      OPG-Fc groups, while BVF recovered only partially and TMD did not recover in the
      vehicle control group. Greatly elevated serum OPG levels and reduced serum TRAP
      5b levels in OPG-Fc-treated animals indicated systemic exposure to locally
      injected drug. The profound decrease in postorthodontic relapse by local OPG-Fc
      administration indicates that osteoclasts are critical to bone maturation
      following tooth movement and points to the potential pharmacologic use of OPG-Fc
      or other RANKL inhibitors for orthodontic retention.

PMID- 22382901
TI  - Aspartic acid substitutions in monoamine oxidase-A reveal both catalytic
      dependent and -independent influences on cell viability and proliferation.
AB  - Post-translational influences could underlie the ambiguous roles of monoamine
      oxidase-A (MAO-A) in pathologies such as depression, cancer and Alzheimer
      disease. In support of this, we recently demonstrated that the Ca2+-sensitive
      component of MAO-A catalytic activity is inhibited by a pro-survival p38 (MAPK)
      dependent mechanism. We substituted three aspartic acid (D) residues in human MAO
      A that reside in putative Ca2+-binding motifs and overexpressed the individual
      proteins in the human HEK293 cell line. We assayed the overexpressed proteins for
      catalytic activity and for their influence on cell viability (using MTT
      conversion and trypan blue exclusion) and proliferation/DNA synthesis [using
      bromodeoxyuridine (BrdU) incorporation]. Innate MAO-A catalytic activity (and the
      capacity for generating hydrogen peroxide) was unaffected by the D61A
      substitution, but inhibited moderately or completely by the D248A and D328G
      substitutions, respectively. The Ca2+-sensitive activities of wild-type and D248A
      MAO-A proteins were enhanced by treatment with the selective p38(MAPK) inhibitor,
      SB203580, but was completely abrogated by the D61A substitution. Monoamine
      oxidase-A(D61A) was toxic to cells and exerted no effect on cell proliferation,
      while MAO-A(D248A) was generally comparable to wild-type MAO-A. As expected, the
      catalytic-dead MAO-A(D328G) was not cytotoxic, but unexpectedly enhanced both MTT
      conversion and BrdU staining. Variant-dependent changes in Bax and Bcl-2/Bcl-XL
      protein expression were observed. A different pattern of effects in N2-a cells
      suggests cell line-dependent roles for MAO-A. A catalytic-dependent mechanism
      influences MAO-A-mediated cytotoxicity, whereas a catalytic-independent mechanism
      contributes to proliferation. Context-dependent inputs by either mechanism could
      underlie the ambiguous pathological contributions of MAO-A.

PMID- 22382902
TI  - Effects of HMG-CoA reductase inhibitor on experimental autoimmune myocarditis.
AB  - PURPOSE: Myocarditis is an acute inflammatory disease of the heart and is often a
      precursor of dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM)
      has been used as a model for human myocarditis. The purpose of this study was to
      investigate the therapeutic role of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG
      CoA) reductase inhibitor, rosuvastatin, on the development of EAM. METHODS:
      Experimental autoimmune myocarditis was induced in BALB/c mice by immunization
      with murine cardiac alpha-myosin heavy chain (MyHc-alpha(614-629) [Ac
      SLKLMATLFSTYASAD-OH]). High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day)
      rosuvastatin or vehicle was administered orally by gastric gavage to mice with
      EAM from day 0 to day 21 after immunization. On day 21 after immunization,
      echocardiography was carried out and the severity of myocarditis was detected by
      histopathological evaluation. Levels of serum tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6 were measured by ELISA. Histopathology was performed using
      haematoxylin and eosin. With apoptosis examined by Tunel, the expression of
      active caspase-3 in myocardium was investigated by immunohistochemistry. RESULTS:
      Rosuvastatin attenuated the histopathological severity of myocarditis. Cardiac
      function was improved in the two rosuvastatin-treated groups compared to the non
      treated EAM group (LVFS: high-dose rosuvastatin group [group H], 0.38 +/- 0.10%;
      low-dose rosuvastatin group [group L], 0.34 +/- 0.06%; non-treated EAM group
      [group N], 0.29 +/- 0.07%. LVEF: group H, 0.80 +/- 0.09%; group L, 0.71 +/-
      0.07%; group N, 0.68 +/- 0.07%). Furthermore, treatment with rosuvastatin
      decreased the expression levels of TNF-alpha (group H, 65.19 +/- 7.06 pg/ml;
      group L, 108.20 +/- 5.28 pg/ml; group N, 239.34 +/- 11.65 pg/ml) and IL-6 (group
      H, 14.33 +/- 2.15 pg/ml; group L, 19.67 +/- 3.04 pg/ml; group N, 40.39 +/- 7.17
      pg/ml). The rates of expression of active Caspase-3 and myocardial apoptosis were
      positively correlated with the scores for myocardial pathology. CONCLUSIONS:
      These results demonstrate that administration of rosuvastatin can ameliorate EAM
      progression, inhibit apoptosis of cardiomyocytes, and preserve cardiac output,
      and they also suggest rosuvastatin may be a promising novel therapeutic strategy
      for the clinical treatment of myocarditis.

PMID- 22382903
TI  - [Jamming a child's finger: an experimental study to determine elastic resistance
      and the point of onset of bone/joint deformation].
AB  - Knowledge of the elastic properties of children's fingers is very important to
      understand the potential hazard for jamming injuries that exists in modern motor
      vehicles with automatic power-operated windows. This study determined the elastic
      resistance and the point of onset of bone/joint deformation at each of 5
      different jam positions of a child's finger under continuous dorsal-palmar
      compression. An unembalmed finger that recently had been surgically removed from
      a polydactylic 8 month-old girl was jammed in a custom hydraulic test apparatus.
      A subminiature force sensor and an electrometric path sensor measured force and
      deflection values. To visualise the respective point of onset of bone/joint
      deformation, jamming of the finger was performed under fluoroscopy. The mean
      force at the point of onset of bone/joint deformation was 78.4 N. The current
      statutory limit of 100 N for the maximum closing force of an automatic power
      operated motor vehicle window is thus well beyond the point at which finger
      injuries can occur in children. Assuming finger injuries in children can occur at
      a jamming force below approximately 80 N, a reduction of the statutory limit to
      us higher than 50 N is reasonable.

PMID- 22382904
TI  - [Results after osteosynthesis of extraarticular proximal phalangeal fractures].
AB  - The aim of the study was to retrospectively present and analyse the functional
      results of surgically treated extraarticular fractures of the proximal
      phalanx.From 1/2005-4/2008 we operated on 49 patients with 52 closed,
      extraarticular fractures of the proximal phalanx of the long fingers with either
      pins, screws or plates. 30 patients were male, 19 were female, the mean age was
      35 years. Open fractures, fractures of the thumb and those with injuries to
      neurovascular structures or tendons were excluded. Postoperative physiotherapy
      was started on day 1 after surgery. Postoperative finger function and
      complications were analysed based on the total active motion (TAM) regarding the
      Belsky score and the classification of Page and Stern. In addition, patients were
      contacted by phone in 4/2009 to verify the subjective functional results at the
      end of the observation period.Three different operative procedures were employed:
      internal fixation by Kirschner wires (n=25), and open fixation by screws (n=8) or
      plates (n=19). The entire treatment period amounted to 12 (4-28) weeks, the
      observation time was 33 (11-50) months. Two patients, both after plate
      osteosynthesis, had to be reoperated because of functional deficits due to
      adhesions. In both a tenolysis and removal of the plate was performed. The
      functional result was excellent in 20 of 25 patients treated by Kirschner wires,
      in seven of the eight in the screw-fixation group and in 13 of the 19 patients
      treated by plate ostheosynthesis (TAM > 240 degrees ); the result was judged fair
      in 1 after plate osteosynthesis (TAM 215 degrees ). The remaining 11 patients
      showed a good outcome with a TAM between 220 degrees  and 239 degrees . These
      favourable results remained subjectively stable at the end of the observation
      period, when all patients could be contacted by phone.Osteosynthesis by kirschner
      wires, screws and plates for closed extraarticular fractures of the proximal
      phalanx of the long fingers gives good to excellent results with few
      complications.

PMID- 22382905
TI  - [Carpal tunnel syndrome in children with mucopolysaccharidosis type 1H: diagnosis
      and therapy in an interdisciplinary centre].
AB  - Carpal tunnel syndrome is common in children with mucopolysaccharidosis type 1H
      (MPS type 1H). Clinical signs of carpal tunnel syndrome are frequently absent in
      these children and it is often very difficult to perform and interpret
      neurophysiological investigations. In this article we wish to present our
      experience and results regarding the diagnosis and postoperative results after
      decompression of the median nerve.In an interdisciplinary set-up we are currently
      treating 11 MPS type 1H children following blood stem cell transplantation. 7
      patients were operated 12 times (5 bilateral operations) because of a carpal
      tunnel syndrome (age at the time of operation 83,3 months, (43-143 months), 2
      male, 5 female). 6 patients had a follow up after 23,7 months (9-59 months). 6
      patients had a histological analysis of the flexor retinaculum. Three patients
      had a postoperative neurophysiological investigation.Each of the operated
      patients had at least 1 preoperative clinical sign of a carpal tunnel syndrome.
      We found at least 1 pathological finding in motor and sensory nerve conduction
      studies in each patient. 6 of the 7 children operated on were symptom-free at
      postoperative follow-up. 1 of the 3 patients with a postoperative
      neurophysiological follow up showed a deterioration of the nerve conduction
      studies. This patient was free of symptoms postoperatively. Biopsy of the flexor
      retinaculum confirmed abundant proteoglycan deposition. We had neither
      postoperative complications nor were revisional operations necessary.The
      Diagnosis of a carpal tunnel syndrome in children with MPS Typ 1H needs a
      thorough medical history, the correct interpretation of the clinical symptoms and
      sophisticated nerve conduction studies. Wether the improvement of the
      postoperative clinical situation lasts has to be evaluated in a long term
      investigation especially because in one patient in our group we saw a
      deterioration of the nerve conduction studies postoperatively.

PMID- 22382906
TI  - [Transfer of the posterior tibialis tendon to restore an active dorsiflexion of
      the foot].
AB  - After lesions of the peroneal nerve or damage of the tibialis anterior muscle a
      lack of active dorsiflexion leads to a drop foot deformity. Ober (1933) described
      a transfer of the posterior tibialis tendon to the dorsum of the foot to restore
      active extension of the foot. The aim of this retrospective study was to evaluate
      the results of this method and to compare our results with those in the
      literature.Between 1992 and 2004 we performed a posterior tibialis tendon
      transfer in 16 patients with an average age of 40 years. 10 patients suffered
      from complete peroneal nerve palsy, which was due to a traumatic lesion (n=8) or
      iatrogenic damage (n=2). 3 patients had an incomplete peroneal nerve palsy caused
      by iatrogenic lesion (n=2) and lumbar disc herniation (n=1). 3 patients
      demonstrated a malfunction of the anterior tibial muscle following a compartment
      syndrome. 14 patients were available for a clinical follow-up after an average of
      64 months. Clinical assessment included the hindfoot, muscular strength, pain,
      limitation of function and subjective satisfaction. The clinical result was
      evaluated using the Stanmore score (0-100).8 patients were very satisfied and 2
      were satisfied with their results, 4 patients were not satisfied. 11 patients had
      no pain. The active dorsal ankle extension averaged  - 5.7 degrees  (10 to  - 30
      degrees ). The Stanmore score revealed an average of 62 points with an excellent
      result in 2, a good result in 5, a fair result in 2 and a poor result in 5
      patients.Transfer of the posterior tibial muscle to restore active dorsiflexion
      of the foot is a therapeutic option. As it is known from the literature objective
      results were mostly fair, but there was a high degree of satisfaction among the
      patients.

PMID- 22382907
TI  - [Treatment of a partial avascular necrosis of a metacarpal head (Morbus Mauclaire
      Dieterich's Disease) utilizing the ostechondral autograft transfer system (OATS)
      technique].
AB  - The OATS (osteochondral autograft transfer system) is a standardized technique
      for the treatment of aseptic osteonecrosis of the knee and ankle. We show the
      first use and successful course of the OAT System for the treatment of a partial
      aseptic necrosis of a metacarpal head.

PMID- 22382908
TI  - [Osteotendocutaneous radial forearm flap for hand reconstruction following
      circular saw injury].
AB  - Circular saw injuries may cause severe damage to the soft tissue of the hand,
      including destruction of skin, tendons and bone. We report the use of an
      osteotendocutaneous radial forearm flap for hand reconstruction following
      circular saw injury. This flap allowed simultaneous reconstruction of skin,
      tendon and osseous defect of the metacarpal bone.

PMID- 22382910
TI  - [Compression of the ulnar nerve at Guyon's canal caused by a pseudoaneurysm of
      the ulnar artery following trauma].
AB  - We repor there on a 16-year-old patient who presented with pain and swelling in
      the hypothenar eminence as well as loss of sensibility in the fingers of the
      region innervated by the ulnar nerve; this happened 2-3 weeks after an injury by
      a glass splinter in his proximal palm. A pseudoaneurysm could be verified by
      duplex sonography. The patient wished to avoid any graft for arterial bridging
      for religious reasons. On the basis of an the Allen test preoperatively and the
      intraoperative findings, an adequate blood supply of the finger by the radial
      artery was expected. Thus, in respect to the patients wish, the aneurysm was
      resected without bridging. The patient recovered perfectly. 4 years later, an MR
      angiography showed the deep and superficial transverse palmar arc to be supplied
      by a voluminous radial artery. The ulnar finger arteries originated from the deep
      arc, the radial finger arteries from the superficial arc. In this paper, the
      criteria pro and contra grafting the ulnar atery at Guyons's canal will be
      discussed.

PMID- 22382909
TI  - [Focal myositis as a side effect of antilipidemics - 2 patients with involvement
      of the forearm].
AB  - Antilipidemics are widely applied to reduce the risk of cardio- and
      cerebrovascular events. The purpose of this case report is to illustrate the
      clinical and radiological findings of focal myositis as a side effect of statins
      and fibrates in 2 patients with forearm involvement. These 2 cases demonstrate
      that a targeted medical history taking and use of MRI to support the suspected
      diagnosis, can efficiently facilitate the route to an appropriate therapy.

PMID- 22382911
TI  - Nuclear cardiology in the literature: a selection of recent original research
      papers.

PMID- 22382914
TI  - Tri-metallic deltahedral Zintl ions: experimental and theoretical studies of the
      novel dimer [(Sn6Ge2Bi)2]4-.
AB  - We report the synthesis, characterization, and computational rationalization of
      the first trimetallic deltahedral Zintl ions. The novel nine-atom clusters were
      structurally characterized as dimers of [(Sn(6)Ge(2)Bi)(2)](4-) with Ge-Ge
      intercluster bonds. They are synthesized either by reacting bimetallic clusters
      (Sn(9-x)Ge(x))(4-) with BiPh(3) or by direct extraction from precursors with
      nominal composition "K(4)Ge(4)Sn(4)Bi".

PMID- 22382915
TI  - Involvement of genes related to inflammation and cell cycle in idiopathic short
      stature.
AB  - Idiopathic Short Stature (ISS) defines a condition in which height is <-2SD
      compared to the mean of a reference population where systemic, endocrinological,
      nutritional or chromosomal disorders have not been identified and diagnosis is
      based on exclusion of any known causes of short stature. JAK/STAT pathway is
      triggered by GH binding to the GH receptor and promotes cellular growth through
      transcription of GH-responsive genes. In order to identify "candidate genes"
      differently expressed in ISS subjects with respect to control ones, we analyzed
      the expression of 84 genes related to JAK/STAT pathway by RT(2) Profiler PCR
      array approach in a total of 10 subjects. Then, we validated the observed data by
      Real Time PCR and ELISA assays in a major number of subjects. We found two genes
      that were differently expressed in ISS subjects with respect to the control
      group: CXCL9 and FCGR1A/CD64, both significantly up-regulated (fold change 2.17
      and 1.70, respectively) and belonging to family of IFN-gamma-inducible factors.
      Further, ISS subjects showed an increased gene expression of IFN-gamma and IFI16,
      higher serum levels of IFN-gamma but similar levels of CXCL9 when compared to
      healthy subjects. In addition, we showed a pubertal modulation of CXCL9 levels.
      These data suggest that inflammatory and regulatory factors of the cell cycle may
      be involved in the ISS condition, introducing a new perspective to its etiology.

PMID- 22382917
TI  - Response of alkaline phosphatases in the cyanobacterium Anabaena sp. FACHB 709 to
      inorganic phosphate starvation.
AB  - Alkaline phosphatases (APases) play a crucial role in phosphorus (P) metabolism
      and regulation, but their physiological functions largely remain unclear in
      cyanobacteria. Here, we identified four putative APase genes, designated as phoA
      709, phoD1-709, phoD2-709, and phoS-709, in the cyanobacterium Anabaena sp. FACHB
      709, and investigated their response to inorganic phosphate (P(i)) starvation.
      With the exception of phoD2-709, three other APase genes were expressed at a
      constant and relative low level in P(i)-replete medium, whereas the expression of
      all four APase genes was elevated in response to P(i) starvation but phoA-709
      significantly. However, disruption of phoA-709 did not affect the total APase
      activity but caused the expressional up-regulation of phoD1-709 and phoS-709
      under P(i)-sufficient and P(i)-limiting conditions. These suggest that, the four
      APases of Anabaena sp. FACHB 709 are involved in P metabolism and regulation, and
      PhoA-709 is the main, yet dispensable, APase.

PMID- 22382918
TI  - Screening for the interacting partners of the proteins MamK & MamJ by two-hybrid
      genomic DNA library of Magnetospirillum magneticum AMB-1.
AB  - Magnetotactic bacteria are a group of prokaryotes capable of sensing and
      navigating along the earth's magnetic field. The linear alignment of
      magnetosomes, which acts as a compass needle for orientation, is dependent on the
      proteins MamJ (amb0964) & MamK (amb0965). We constructed Magnetospirillum
      magneticum AMB-1 two-hybrid DNA libraries by fusing the random genomic fragments
      of AMB-1 to the N-terminal domain of the alpha-subunit of RNA polymerase in
      vector pTRG and used as preys. The genes mamJ & mamK were cloned in frame with
      the lambda repressor protein (lambda cI) in vector pBT and used as baits for
      screening the binding partners. After preliminary screening, we further confirmed
      the candidate interactions between selected protein pairs. The results showed
      that there were relatively strong interactions between MamK versus Amb3498
      (flagella motor switch protein fliM), versus Amb0854 MCPs (signal domain of
      methyl-accepting chemotaxis protein) and versus Amb3568 (GGDEF domain-containing
      protein), respectively. MamJ versus Amb1722 (hypothetical protein), MamJ versus
      MamK, and MamK versus Amb1807 (cation transport ATPase) exhibited low level of
      interaction. Although the TPR repeat protein MamA (amb0971) showed no interaction
      with either MamJ or MamK, the TPR repeat protein Amb0024 with more motif
      sequences exhibited relatively strong interaction with MamK. Among the identified
      proteins, all categorized as signal transduction-related displayed interaction
      only with MamK and without MamJ, suggesting that magnetotaxis via MamK in
      Magnetospirillum magneticum AMB-1 might be somehow concerned with the widely
      accepted chemotaxis mechanism in bacteria.

PMID- 22382919
TI  - Deprotonation of C-alkyl groups of cationic N-heterocyclic ligands.
AB  - The C-alkyl groups of C-alkylpyrazinium-derived ligands have been selectively
      deprotonated by K[N(SiMe(3))(2)], through charge-controlled processes, to give
      neutral products that contain C-alkylidenepyrazine-derived ligands.

PMID- 22382921
TI  - Molecular probes of solvation phenomena.
AB  - The properties of the molecules present in any chemical or biological system are
      dependent on interactions with the environment, and a quantitative understanding
      of solvation phenomena remains a major challenge. Molecular recognition probes
      provide a new approach to quantitatively measure the properties of solvents.
      Traditionally, solvent polarity scales have been based on spectroscopic probes
      that provide insight into the nature of solvent-solute interactions. This review
      compares the solvent polarity parameters obtained from the wavelengths of
      UV/Visible absorption maxima with solute H-bond parameters obtained from the free
      energies of solution equilibria. The similarity of the solvent and solute H-bond
      scales leads to a general H-bond scale that uses the same parameters to describe
      both solvent and solute. The general H-bond scale provides a framework for
      understanding the relationship between local intermolecular interactions and the
      properties of the bulk medium. Intermolecular interactions are sensitive to
      solvation equilibria, so molecular recognition probes provide fundamentally
      different information from spectroscopic probes that are sensitive to the
      populations of different solvation states of the solute. Studies of mixed
      solvents demonstrate the potential of molecular recognition probes for providing
      new insights into solvation phenomena.

PMID- 22382920
TI  - Impact of non invasive and beat-to-beat arterial pressure monitoring on
      intraoperative hemodynamic management.
AB  - The Nexfin device allows for non-invasive beat-to-beat blood pressure monitoring
      (BP(NXF)). Perioperative hypotension and hypertension have been shown to be
      associated with poor clinical outcomes. The goal of the present study was to
      assess the ability of this device to decrease the duration of significant
      intraoperative hypo- or hypertension compared to standard BP monitoring by cuff
      (BP(CUFF)). We studied25 patients (ASA I-III) undergoing either abdominal or
      orthopedic surgery. BP(CUFF) was monitored every 5 min from the introduction of
      anesthesia, while BP(NXF) was monitored continuously on the opposite arm. When
      systolic BP(NXF) (SBP(NXF)) decreased or increased more than 20% relative to
      baseline SBP(NXF), a standard BP(CUFF) measurement was taken to compare values.
      In addition, the time interval between the 20% change in SBP(NXF) and the next
      scheduled standard SBP(CUFF) measurement was recorded for each event. The mean
      length of surgery was 3.0 +/- 0.3 h. Patients presented with 11 +/- 4 episodes of
      hypotension and 12 +/- 4 episodes of hypertension during the surgery. If BP(CUFF)
      had been used, this would have resulted in 21 +/- 7 min of hypotension and 20 +/-
      10 min of hypertension. If hemodynamic changes seen by SBP(NXF) were
      appropriately treated, an average of 7 +/- 1 min/h of hypotension time, 7 +/- 2
      min/h of hypertension time and 14 +/- 3 min per hour of hypo- or hypertension
      time may have been identified. The Nexfin BP has the potential to decrease the
      time of hypotension and hypertension compared to conventional intermittent
      BP(CUFF) monitoring. Therefore, this device has the potential to positively
      impact clinical outcomes.

PMID- 22382913
TI  - Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL-
      GA2LEN--ARIA position paper.
AB  - Concepts of disease severity, activity, control and responsiveness to treatment
      are linked but different. Severity refers to the loss of function of the organs
      induced by the disease process or to the occurrence of severe acute
      exacerbations. Severity may vary over time and needs regular follow-up. Control
      is the degree to which therapy goals are currently met. These concepts have
      evolved over time for asthma in guidelines, task forces or consensus meetings.
      The aim of this paper is to generalize the approach of the uniform definition of
      severe asthma presented to WHO for chronic allergic and associated diseases
      (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in
      order to have a uniform definition of severity, control and risk, usable in most
      situations. It is based on the appropriate diagnosis, availability and
      accessibility of treatments, treatment responsiveness and associated factors such
      as comorbidities and risk factors. This uniform definition will allow a better
      definition of the phenotypes of severe allergic (and related) diseases for
      clinical practice, research (including epidemiology), public health purposes,
      education and the discovery of novel therapies.

PMID- 22382922
TI  - Neuroscience may supersede ethics and law.
AB  - Advances in technology now make it possible to monitor the activity of the human
      brain in action, however crudely. As this emerging science continues to offer
      correlations between neural activity and mental functions, mind and brain may
      eventually prove to be one. If so, such a full comprehension of the
      electrochemical bases of mind may render current concepts of ethics, law, and
      even free will irrelevant.

PMID- 22382923
TI  - Medical students' decisions about authorship in disputable situations:
      intervention study.
AB  - In medicine, professional behavior and ethics are often rule-based. We assessed
      whether instruction on formal criteria of authorship affected the decision of
      students about authorship dilemmas and whether they perceive authorship as a
      conventional or moral concept. A prospective non-randomized intervention study
      involved 203s year medical students who did (n = 107) or did not (n = 96)
      received a lecture on International Committee of Medical Journal editors (ICMJE)
      authorship criteria. Both groups had to read 3 vignettes and answer 4 questions
      related to the distinction between conventional and moral domains. Written
      justification of student' choices whether the authorship in a vignette was right
      or wrong was rated by 4 independent raters as based on justice or a rule. Formal
      instruction had no effect on students' decisions on authorship in the vignettes
      (44, 34 and 39% ICMJE-consistent answers for 3 vignettes, respectively, by
      students receiving instruction vs. 38, 42 and 30% for those without instruction;
      P > 0.161 for all vignettes). For all dilemmas, more students decided contrary to
      ICMJE criteria and considered their decisions to be a matter of obligation and
      not a choice and to be general across situations and sciences. They were willing
      to change their decision if a rule was different only for peer situations but not
      for mentor-mentee situations. The number of students who used rule-based
      justification of their ICMJE criteria-consistent decisions was significantly
      higher in the instructed than in the uninstructed group. Instruction about formal
      authorship criteria had no effect on student's decisions about authorship
      dilemmas and their decisions were related to the moral rather than a conventional
      domain. Teaching about authorship and other professionalism and integrity issues
      may benefit from interventions that bring intuitive processes into awareness
      instead of those fostering rule-based reasoning.

PMID- 22382924
TI  - Airway basal cell vascular endothelial growth factor-mediated cross-talk
      regulates endothelial cell-dependent growth support of human airway basal cells.
AB  - The human airway epithelium is a pseudostratified heterogenous layer comprised of
      ciliated, secretory, intermediate, and basal cells. As the stem/progenitor
      population of the airway epithelium, airway basal cells differentiate into
      ciliated and secretory cells to replenish the airway epithelium during
      physiological turnover and repair. Transcriptome analysis of airway basal cells
      revealed high expression of vascular endothelial growth factor A (VEGFA), a gene
      not typically associated with the function of this cell type. Using cultures of
      primary human airway basal cells, we demonstrate that basal cells express all of
      the three major isoforms of VEGFA (121, 165 and 189) but lack functional
      expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is
      actively secreted by basal cells and while it appears to have no direct autocrine
      function on basal cell growth and proliferation, it functions in a paracrine
      manner to activate MAPK signaling cascades in endothelium via VEGFR2-dependent
      signaling pathways. Using a cytokine- and serum-free co-culture system of primary
      human airway basal cells and human endothelial cells revealed that basal cell
      secreted VEGFA activated endothelium to express mediators that, in turn,
      stimulate and support basal cell proliferation and growth. These data demonstrate
      novel VEGFA-mediated cross-talk between airway basal cells and endothelium, the
      purpose of which is to modulate endothelial activation and in turn stimulate and
      sustain basal cell growth.

PMID- 22382925
TI  - Emerging roles of immunoproteasomes beyond MHC class I antigen processing.
AB  - The proteasome is a multi-catalytic protein complex whose primary function is the
      degradation of abnormal or foreign proteins. Upon exposure of cells to
      interferons (IFNs), the beta1i/LMP2, beta2i/MECL-1, and beta5i/LMP7 subunits are
      induced and incorporated into newly synthesized immunoproteasomes (IP), which are
      thought to function solely as critical players in the optimization of the CD8(+)
      T-cell response. However, the observation that IP are present in several non
      immune tissues under normal conditions and/or following pathological events
      militates against the view that its role is limited to MHC class I presentation.
      In support of this concept, the recent use of genetic models deficient for
      beta1i/LMP2, beta2i/MECL-1, or beta5i/LMP7 has uncovered unanticipated functions
      for IP in innate immunity and non-immune processes. Herein, we review recent data
      in an attempt to clarify the role of IP beyond MHC class I epitope presentation
      with emphasis on its involvement in the regulation of protein homeostasis, cell
      proliferation, and cytokine gene expression.

PMID- 22382926
TI  - Sex chromosome inactivation in germ cells: emerging roles of DNA damage response
      pathways.
AB  - Sex chromosome inactivation in male germ cells is a paradigm of epigenetic
      programming during sexual reproduction. Recent progress has revealed the
      underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger
      of chromosome-wide silencing is activation of the DNA damage response (DDR)
      pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a
      binding partner of phosphorylated histone H2AX (gammaH2AX). This DDR pathway
      shares features with the somatic DDR pathway recognizing DNA replication stress
      in the S phase. Additionally, it is likely to be distinct from the DDR pathway
      that recognizes meiosis-specific double-strand breaks. This review article
      extensively discusses the underlying mechanism of sex chromosome inactivation.

PMID- 22382928
TI  - Geographic difference in advanced gastric cancer prevalence and chemotherapy
      treatment results: could it really be an independent prognostic factor?

PMID- 22382929
TI  - A systematic review of patient surveillance after curative gastrectomy for
      gastric cancer: a brief review.
AB  - BACKGROUND: Complete resection of a gastric cancer and adjacent lymph nodes
      offers the only chance for cure of the disease. However, disease recurrence
      occurs in 22-51% of cases, and its prognosis is very poor. Many clinicians
      perform post-operative follow-up for these patients, although there is no
      consensus on the regimen, frequency of visits, mode of testing, or the rationale
      of a follow-up program. PURPOSE: The objective of this systematic review was to
      identify the evidence for surveillance in patients with resected gastric cancer,
      specifically examining the interval of follow-up and the modalities utilized.
      METHODS: Electronic literature searches were conducted using Medline, Embase, and
      the Cochrane Central Register of Controlled Trials from January 1st 1998 to
      December 1st 2009. All search titles and abstracts were independently rated for
      relevance by a minimum of two reviewers. RESULTS: Five articles were selected. A
      total of 810 patients underwent post-operative follow-up. History and physical
      examination, hematological and chemistry profile, endoscopy
      (esophagogastroduodenoscopy [EGD]), and computed tomography (CT) were the most
      frequently employed modalities. CT detected the majority of recurrences in the
      included studies. The survival post-recurrence was significantly higher in the
      asymptomatic group compared with symptomatic group in three studies, but this may
      simply reflect lead-time bias. No differences in overall survival (OS) were
      found. CONCLUSION: The included studies failed to show an improvement in OS with
      more intense surveillance. Further prospective studies are required to determine
      whether a subgroup of patients may benefit from more intensive follow-up.

PMID- 22382930
TI  - Endoscopic submucosal dissection for gastric neoplasm in patients with co
      morbidities categorized according to the ASA Physical Status Classification.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has come to be widely
      performed for reduced invasiveness; however, its safety in patients with co
      morbidities is not fully examined. We aimed to evaluate the safety and efficacy
      of gastric ESD with co-morbidities categorized according to ASA Physical Status
      Classification. METHODS: Two hundred and forty patients of ASA 1 (no co
      morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD
      for gastric neoplasms. We retrospectively compared clinicopathological features
      and treatment results of these three groups. RESULTS: Cases (by percent) treated
      with anticoagulant/platelet agents were more common in the higher ASA grades (ASA
      1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P < 0.0001). There were no significant
      differences in case numbers treated under guideline criteria, curative resection
      (ASA 1, 79.6%; ASA 2, 79.9%; ASA 3, 78.9%), or complications related to the ESD
      procedure (e.g., postoperative bleeding, perforation, thermal injury). By a
      patient risk prediction model on surgery, i.e., P-POSSUM, morbidity was halved,
      and no patients died compared to a predicted death rate of 0.5-2%; however, total
      and complications unrelated to ESD procedure (e.g., aspiration pneumonia,
      ischemic heat attack) were more common in higher ASA grades (ASA 1, ASA 2, ASA 3:
      15.4, 23.9, 26.3%, respectively, P = 0.014; 0.4, 7.1, 0%, respectively, P =
      0.00087). Deviation rates from clinical pathway were more frequent and hospital
      stay (days) longer in higher ASA grades (ASA 1, ASA 2, ASA 3: 11.3, 17.9, 26.3%,
      respectively, P = 0.014; 8, 8, 9%, respectively, P = 0.0053). CONCLUSIONS: ESD is
      an efficient treatment for gastric neoplasms with co-morbidities. However,
      additional caution is required because co-morbidity is a risk factor for both
      total complications and complications unrelated to the ESD procedure, and may
      cause deviations in the clinical course and prolonged hospital stay.

PMID- 22382931
TI  - Removal of a nail from bone after nail gun injury:  a case report and utility of
      a classic technique.
AB  - Nail gun injuries are common, work-related injuries that typically involve bony
      impalement of an extremity with the nail. Treatment recommendations are well
      established, although suggestions for removing the nail itself have been lacking.
      In our hands, removal using typical operating room equipment has been
      challenging, usually resulting in nail head deformity and breakage, which makes
      completing the procedure even more difficult. As a result, we have revisited the
      tool designed solely for the purpose of nail removal, that is, a claw hammer:
      this tool is readily available from materials management at most hospitals, can
      be easily autoclaved, and is effectively used with a block or surgical pan lid to
      gain leverage and protect the soft tissues. We have found this method to be
      simple and extremely useful for nail removal for the nail-impaled patient.

PMID- 22382927
TI  - Role of the ubiquitin-proteasome system in nervous system function and disease:
      using C. elegans as a dissecting tool.
AB  - In addition to its central roles in protein quality control, regulation of cell
      cycle, intracellular signaling, DNA damage response and transcription regulation,
      the ubiquitin-proteasome system (UPS) plays specific roles in the nervous system,
      where it contributes to precise connectivity through development, and later
      assures functionality by regulating a wide spectrum of neuron-specific cellular
      processes. Aberrations in this system have been implicated in the etiology of
      neurodevelopmental and neurodegenerative diseases. In this review, we provide an
      updated view on the UPS and highlight recent findings concerning its role in
      normal and diseased nervous systems. We discuss the advantages of the model
      organism Caenorhabditis elegans as a tool to unravel the major unsolved questions
      concerning this biochemical pathway and its involvement in nervous system
      function and dysfunction, and expose the new possibilities, using state-of-the
      art techniques, to assess UPS function using this model system.

PMID- 22382932
TI  - Coping patterns and their relation to daily activity, worries, depressed mood,
      and pain intensity in acute whiplash-associated disorders.
AB  - BACKGROUND: There is a lack of knowledge regarding how individuals with acute
      whiplash-associated disorders (WAD) appraise and cope with situation-specific
      stressors. PURPOSE: The aim of the study was to describe the daily process of
      coping reported in a daily coping assessment by individuals with acute WAD within
      1 month after the accident. More specifically, profiles of coping strategies were
      identified and patterns between stressors, primary and secondary appraisals, and
      coping strategy profiles were described in relation to reported level of
      activity, worries, depressed mood and pain intensity during the day. METHOD: A
      descriptive and exploratory design was applied. Two hundred and twenty-nine
      whiplash-associated disorders-daily coping assessment (WAD-DCA) collected during
      seven consecutive days from 51 participants with acute WAD in Sweden, were
      included. Cluster analysis was used to obtain coping strategy profiles and data
      were graphically visualised as patterns through the coping process. RESULTS: When
      measuring coping as a daily process relating to the specific stressful situation,
      different coping process patterns appeared. During days with a high degree of
      physical and mental well-being, high self-efficacy beliefs seemed to be working
      as an important secondary appraisal, whereas during days with a low degree of
      physical and mental well-being primary appraisals of the stressor as a threat and
      catastrophic thoughts were present in the coping process. CONCLUSIONS: Early
      identification of situational- and individual-specific stressors, appraisals and
      coping efforts as measured by the WAD-DCA may contribute to the understanding of
      the coping process in the acute stage of WAD and its possible impact on recovery
      and adjustment.

PMID- 22382933
TI  - The effect of different treatment modalities on the calcification potential and
      cross-linking stability of bovine pericardium.
AB  - Porcine heart valves and bovine pericardium exhibit suitable properties for use
      as substitutes in cardiothoracic surgery, but must meet several requirements to
      be safe and efficient. Treatment with glutaraldehyde (GA) render some of these
      requirements, but calcification and degradation post-implant remain a problem.
      This study aimed to identify additional biochemical treatments that will minimize
      calcification potential without compromising the physical properties of
      pericardium. Pericardium treated with GA calcified severely after 8 weeks in the
      subcutaneous rat model, compared to tissue treated with higher concentrations of
      glycosaminoglycans (GAG) and commercial Glycar patches. GA, lower concentrations
      GAG and Glycar pericardium had high denaturation temperatures due to enhanced
      cross-linking. Tensile strength of GA tissue was significantly lower than GAG
      treated or Glycar tissues, due to lower water content with resultant lower
      flexibility and suppleness. Pericardium treated with 0.01 M GAG gave acceptable
      denaturation temperatures, tensile strength and reduced calcification potential.
      All tissue treatments evoked comparable host immune responses, and no significant
      difference in resistance to enzymatic degradation. Ineffective stabilization and
      fixation of cross-links following GAG treatment, as well as limited penetration
      into the pericardium, resulted in GAG leaching out into the surrounding host
      tissue or storage medium, and prohibits safe clinical use of such tissue.

PMID- 22382934
TI  - Age associated differences in prevalence of individual rotterdam criteria and
      metabolic risk factors during reproductive age in 446 caucasian women with
      polycystic ovary syndrome.
AB  - Clinical manifestations and metabolic risk factors may differ according to age in
      patients with polycystic ovary syndrome (PCOS). Therefore, a retrospective trans
      sectional study in academic tertiary-care medical center was designed. A cohort
      of 446 premenopausal, Caucasian women (age range 15-49 years) with PCOS were
      divided into 4 subgroups according to age: group 1 (15-19 years, n=42), group 2
      (20-29 years, n=180), group 3 (30-39 years, n=187), group 4 (40-49 years, n=37)
      and underwent clinical evaluation (Ferriman-Gallwey score, BMI, waist, blood
      pressure), hormone analyses (sex hormones, fasting lipids, insulin, glucose),
      transvaginal ultrasound, oral glucose tolerance tests (OGTT) (n=234), and ACTH
      tests (n=201). BMI, waist, Ferriman-Gallwey score, blood pressure, and lipid
      profile were higher in older vs. younger age groups whereas androgen levels were
      lower. Measures of insulin resistance were unchanged between age groups, but
      glucose levels were significantly higher in older age groups. Rotterdam criteria:
      The prevalence of PCO and biochemical hyperandrogenism decreased in the oldest
      age group whereas clinical hyperandrogenism increased. Young patients are
      characterized by PCO and biochemical hyperandrogenism, whereas older patients are
      more obese with more severe hirsutism and more cardiovascular and metabolic risk
      factors.

PMID- 22382935
TI  - Regioselective heterohalogenation of 4-halo-anisoles via a series of sequential
      ortho-aluminations and electrophilic halogenations.
AB  - As the aluminate base [LiAl(TMP)(2)(iBu)(2)] 1 displays halogen tolerance towards
      substituted aromatics, 4-halo-anisoles have been ortho-aluminated and
      electrophilically quenched to form synthetically useful multi-heterohalogenated
      anisoles, with the Al intermediates along the route structurally defined.

PMID- 22382936
TI  - Microwave-assisted synthesis of BSA-protected small gold nanoclusters and their
      fluorescence-enhanced sensing of silver(I) ions.
AB  - A one-step microwave-assisted method is used for the synthesis of small gold
      nanoclusters, Au(16)NCs@BSA, which are used as a fluorescence enhanced sensor for
      detection of silver(I) ions with high selectivity and sensitivity.

PMID- 22382937
TI  - Intensification of electrochemiluminescence of luminol on TiO2 supported Au
      atomic cluster nano-hybrid modified electrode.
AB  - With TiO(2) nanoparticles as carrier, a supported nano-material of Au atomic
      cluster/TiO(2) nano-hybrid was synthesized. It was then modified onto the surface
      of indium tin oxide (ITO) by Nafion to act as a working electrode for exciting
      the electrochemiluminescence (ECL) of luminol. The properties of the nano-hybrid
      and the modified electrode were characterized by XRD, XPS, electronic microscopy,
      electrochemistry and spectroscopy. The experimental results demonstrated that the
      modification of this nano-hybrid onto the ITO electrode efficiently intensified
      the ECL of luminol. It was also revealed that the ECL intensity of luminol on
      this modified electrode showed very sensitive responses to oxygen and hydrogen
      peroxide. The detection limits for dissolved oxygen and hydrogen peroxide were 2
      MUg L(-1) and 5.5 * 10(-12) M, respectively. Besides the discussion of the
      intensifying mechanism of this nano-hybrid for ECL of luminol, the developed
      method was also applied for monitoring dissolved oxygen and evaluating the
      scavenging efficiency of reactive oxygen species of the Ganoderma lucidum spore.

PMID- 22382938
TI  - The great beyond.

PMID- 22382939
TI  - The darker side of stem cells.

PMID- 22382940
TI  - Frozen out.

PMID- 22382941
TI  - Clear up this fuzzy thinking on brain scans.

PMID- 22382952
TI  - Stem-cell therapy takes off in Texas.

PMID- 22382953
TI  - Protests delay Greek university reform.

PMID- 22382954
TI  - Structural biologists share their toys.

PMID- 22382955
TI  - Egg-making stem cells found in adult ovaries.

PMID- 22382956
TI  - Timing glitches dog neutrino claim.

PMID- 22382957
TI  - Plans stall for biodefence lab.

PMID- 22382958
TI  - US disease agency in fiscal peril.

PMID- 22382959
TI  - Rare diseases: Genomics, plain and simple.

PMID- 22382960
TI  - Treating schizophrenia: Game on.

PMID- 22382961
TI  - Archaeology: A clash of symbols.

PMID- 22382962
TI  - Synthetic biology: Four steps to avoid a synthetic-biology disaster.

PMID- 22382963
TI  - Sustainability: Tax 'societal ills' to save the planet.

PMID- 22382968
TI  - Crime: track illegal trade in wildlife.

PMID- 22382969
TI  - Citations: results differ by database.

PMID- 22382970
TI  - Informed consent: cultural differences.

PMID- 22382971
TI  - Informed consent: meet patients' needs.

PMID- 22382972
TI  - Citations: not all measures are equal.

PMID- 22382973
TI  - Planetary science: In search of biosignatures.

PMID- 22382974
TI  - Social science: Carrot or stick?

PMID- 22382975
TI  - Palaeobotany: In the shade of the oldest forest.

PMID- 22382976
TI  - Catalysis: Disguise gets a reaction.

PMID- 22382977
TI  - Microfluidics: Analog-to-digital drug screening.

PMID- 22382978
TI  - Translational medicine: Primed for resistance.

PMID- 22382979
TI  - Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2.
AB  - Ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers such as SUMO (also known as
      Smt3 in Saccharomyces cerevisiae) mediate signal transduction through post
      translational modification of substrate proteins in pathways that control
      differentiation, apoptosis and the cell cycle, and responses to stress such as
      the DNA damage response. In yeast, the proliferating cell nuclear antigen PCNA
      (also known as Pol30) is modified by ubiquitin in response to DNA damage and by
      SUMO during S phase. Whereas Ub-PCNA can signal for recruitment of translesion
      DNA polymerases, SUMO-PCNA signals for recruitment of the anti-recombinogenic DNA
      helicase Srs2. It remains unclear how receptors such as Srs2 specifically
      recognize substrates after conjugation to Ub and Ubls. Here we show, through
      structural, biochemical and functional studies, that the Srs2 carboxy-terminal
      domain harbours tandem receptor motifs that interact independently with PCNA and
      SUMO and that both motifs are required to recognize SUMO-PCNA specifically. The
      mechanism presented is pertinent to understanding how other receptors
      specifically recognize Ub- and Ubl-modified substrates to facilitate signal
      transduction.

PMID- 22382980
TI  - Biosignatures as revealed by spectropolarimetry of Earthshine.
AB  - Low-resolution intensity spectra of Earth's atmosphere obtained from space reveal
      strong signatures of life ('biosignatures'), such as molecular oxygen and methane
      with abundances far from chemical equilibrium, as well as the presence of a 'red
      edge' (a sharp increase of albedo for wavelengths longer than 700 nm) caused by
      surface vegetation. Light passing through the atmosphere is strongly linearly
      polarized by scattering (from air molecules, aerosols and cloud particles) and by
      reflection (from oceans and land). Spectropolarimetric observations of local
      patches of Earth's sky light from the ground contain signatures of oxygen, ozone
      and water, and are used to characterize the properties of clouds and aerosols.
      When applied to exoplanets, ground-based spectropolarimetry can better constrain
      properties of atmospheres and surfaces than can standard intensity spectroscopy.
      Here we report disk-integrated linear polarization spectra of Earthshine, which
      is sunlight that has been first reflected by Earth and then reflected back to
      Earth by the Moon. The observations allow us to determine the fractional
      contribution of clouds and ocean surface, and are sensitive to visible areas of
      vegetation as small as 10 per cent. They represent a benchmark for the
      diagnostics of the atmospheric composition, mean cloud height and surfaces of
      exoplanets.

PMID- 22382981
TI  - Catalytic functionalization of unactivated primary C-H bonds directed by an
      alcohol.
AB  - New synthetic methods for the catalytic functionalization of C-H bonds have the
      potential to revolutionize the synthesis of complex molecules. However, the
      realization of this synthetic potential requires the ability to functionalize
      selectively one C-H bond in a compound containing many such bonds and an array of
      functional groups. The site-selective functionalization of aliphatic C-H bonds is
      one of the greatest challenges that must be met for C-H bond functionalization to
      be used widely in complex-molecule synthesis, and processes catalysed by
      transition-metals provide the opportunity to control selectivity. Current methods
      for catalytic, aliphatic C-H bond functionalization typically rely on the
      presence of one inherently reactive C-H bond, or on installation and subsequent
      removal of directing groups that are not components of the desired molecule. To
      overcome these limitations, we sought catalysts and reagents that would
      facilitate aliphatic C-H bond functionalization at a single site, with
      chemoselectivity derived from the properties of the catalyst and site-selectivity
      directed by common functional groups contained in both the reactant and the
      desired product. Here we show that the combination of an iridium-phenanthroline
      catalyst and a dihydridosilane reagent leads to the site-selective gamma
      functionalization of primary C-H bonds controlled by a hydroxyl group, the most
      common functional group in natural products. The scope of the reaction
      encompasses alcohols and ketones bearing many substitution patterns and auxiliary
      functional groups; this broad scope suggests that this methodology will be
      suitable for the site-selective and diastereoselective functionalization of
      complex natural products.

PMID- 22382982
TI  - Continental collision slowing due to viscous mantle lithosphere rather than
      topography.
AB  - Because the inertia of tectonic plates is negligible, plate velocities result
      from the balance of forces acting at plate margins and along their base.
      Observations of past plate motion derived from marine magnetic anomalies provide
      evidence of how continental deformation may contribute to plate driving forces. A
      decrease in convergence rate at the inception of continental collision is
      expected because of the greater buoyancy of continental than oceanic lithosphere,
      but post-collisional rates are less well understood. Slowing of convergence has
      generally been attributed to the development of high topography that further
      resists convergent motion; however, the role of deforming continental mantle
      lithosphere on plate motions has not previously been considered. Here I show that
      the rate of India's penetration into Eurasia has decreased exponentially since
      their collision. The exponential decrease in convergence rate suggests that
      contractional strain across Tibet has been constant throughout the collision at a
      rate of 7.03 * 10(-16) s(-1), which matches the current rate. A constant bulk
      strain rate of the orogen suggests that convergent motion is resisted by constant
      average stress (constant force) applied to a relatively uniform layer or
      interface at depth. This finding follows new evidence that the mantle lithosphere
      beneath Tibet is intact, which supports the interpretation that the long-term
      strain history of Tibet reflects deformation of the mantle lithosphere. Under
      conditions of constant stress and strength, the deforming continental lithosphere
      creates a type of viscous resistance that affects plate motion irrespective of
      how topography evolved.

PMID- 22382983
TI  - Surprisingly complex community discovered in the mid-Devonian fossil forest at
      Gilboa.
AB  - The origin of trees by the mid-Devonian epoch (398-385 million years ago) signals
      a major change in terrestrial ecosystems with potential long-term consequences
      including increased weathering, drop in atmospheric CO(2), modified climate,
      changes in sedimentation patterns and mass extinction. However, little is known
      about the ecology of early forests or how changes in early terrestrial ecosystems
      influenced global processes. One of the most famous palaeontological records for
      this time is the 'oldest fossil forest' at Riverside Quarry, Gilboa, New York,
      USA, discovered in the 1920s. Hundreds of large Eospermatopteris sandstone casts,
      now thought to represent the bases of standing cladoxylopsid trees, were
      recovered from a horizon that was originally interpreted as a muddy swamp. After
      quarry operations ceased, relatively minor outcrops of similar fossils at nearby
      localities have provided limited opportunities to evaluate this pervasive view
      using modern methods. In 2010, removal of the quarry backfill enabled reappraisal
      of the palaeoecology of this important site. Here we describe a 1,200 m(2) map
      showing numerous Eospermatopteris root systems in life position within a mixed
      age stand of trees. Unexpectedly, large woody rhizomes with adventitious roots
      and aerial branch systems identified as aneurophytalean progymnosperms run
      between, and probably climb into, Eospermatopteris trees. We describe the overall
      habit for these surprisingly large aneurophytaleans, the earliest fossil group
      having wood produced by a bifacial vascular cambium. The site also provides
      evidence for arborescence within lycopsids, extending the North American range
      for trees in this ecologically critical group. The rooting horizon is a dark grey
      sandy mudstone showing limited root penetration. Although clearly belonging to a
      wetland coastal plain environment, the forest was probably limited in duration
      and subject to periodic disturbance. These observations provide fundamental
      clarification of the palaeoecology of this mixed-group early forest, with
      important implications for interpreting coeval assemblage data worldwide.

PMID- 22382985
TI  - Expression of KRT7 and WT1 differentiates precursor lesions of Wilms' tumours
      from those of papillary renal cell tumours and mucinous tubular and spindle cell
      carcinomas.
AB  - Wilms' tumours (WT) and adult papillary renal cell tumours (pRCT) are associated
      with precursor lesions of embryonic origin. The aim of this study was to analyse
      the expression of WT1, KRT7, KRT8, KRT18 and KRT19 genes by immunohistochemistry
      in 74 precursor lesions associated with WTs, pRCTs and mucinous tubular and
      spindle cell carcinomas (MTSCC). All precursor lesions associated with Wilms'
      tumours were positive for WT1, whereas all precursor lesions in pRCT and MTSCC
      bearing kidneys were negative. None of the WT-associated lesions were positive
      for KRT7, but 69-80% of lesions associated with pRCTs and MTSCCs were positive
      for KRT7. KRT8, KRT18 and KRT19 were found to be expressed in 80-100% of all
      types of precursor lesions. Our findings indicate that the precursor lesions
      analysed in this study are committed in an early stage of cellular
      differentiation to the development of either Wilms' tumours or papillary RCTs and
      MTSCCs.

PMID- 22382986
TI  - The management of injuries to the medial side of the knee.
AB  - Injuries to the medial side of the knee are the most common knee ligament
      injuries. The majority of injuries occur in young athletes during sporting
      events, with the usual mechanism involving a valgus contact, tibial external
      rotation, or a combined valgus and external rotation force delivered to the knee.
      Although most complete grade III medial knee injuries heal, some do not, which
      can lead to continued instability. For these patients, a thorough understanding
      of the presenting history and a physical examination are important because these
      injuries can often be confused with posterolateral corner injuries. The main
      anatomic structures of the medial side of the knee are the superficial medial
      collateral ligament, deep medial collateral ligament, and posterior oblique
      ligament. In addition, accurately locating 3 bony prominences over the medial
      aspect of the knee-the adductor tubercle, gastrocnemius tubercle, and medial
      epicondyle-is important to conduct a proper physical examination and for surgical
      repairs and reconstructions. Clinical diagnosis of medial knee injuries is
      primarily performed via the application of a valgus stress in full extension and
      at 30 degrees  of knee flexion. In addition, an examination of the amount of
      anteromedial tibial rotation is performed at 90 degrees  of flexion, while the
      dial test, performed at 30 degrees  and 90 degrees  of flexion, is important
      because it evaluates for rotational abnormalities. Valgus stress radiographs are
      useful to objectively determine the amount of medial compartment gapping and to
      discern whether there is medial or lateral compartment gapping when a medial or
      posterolateral corner knee injury cannot be differentiated, especially with a
      chronic injury. The majority of acute grade III medial knee injuries will heal
      after a nonoperative rehabilitation program. In most instances when there is a
      knee dislocation or multiligament injury, a primary repair with sutures may be
      indicated. In severe midsubstance injuries or chronic medial knee injuries, an
      anatomic medial knee reconstruction with grafts may be indicated. Rehabilitation
      principles for acute medial knee injuries involve controlling edema, regaining
      range of motion, and avoiding any significant stress on the healing ligaments. A
      well-guided rehabilitation program can result in excellent functional outcomes in
      the majority of patients.

PMID- 22382987
TI  - Comments on article by Kinsella et al. published in the November 2011 issue.

PMID- 22382988
TI  - Placebo effect model in asthma clinical studies: longitudinal meta-analysis of
      forced expiratory volume in 1 second.
AB  - OBJECTIVE: Our objective was to describe the time course of the placebo effect in
      asthma and quantitatively investigate the affective factors of the placebo effect
      for the placebo response simulation during the asthma clinical study design.
      METHODS: We conducted a systemic search of public data sources for the study
      level forced expiratory volume in 1 second (FEV(1)) to build the placebo effect
      model for studies by oral or inhaled administrations simultaneously. The
      administration routes, types of inhalation device, mean patient age, mean male
      proportion, baseline FEV(1), disease severity, year of publication, inhaled
      corticosteroid status during the treatment, and dropout rate were tested as
      covariates. RESULTS: There are 34 literature sources containing 178 mean values
      for FEV(1) presenting the individual observations from about 3,703 patients. The
      exponential models adequately described the time course of placebo effect with
      the typical value of the maximum placebo effect (P(max)) of 0.060 L. Dropout rate
      incorporated in the residual error model and the disease severity (mild to
      moderate and moderate to severe) at baseline were covariates that remained in the
      final model. CONCLUSIONS: The placebo effect is adequately described by an
      exponential model over time. By incorporating the dropout rate in the residual
      error model, the estimation precision was improved. The model could predict the
      placebo response profile in mild to severe asthmatic patients for the asthma
      clinical study design and could also be a structure model of the placebo effect
      for the pure drug effect evaluation in the asthma clinical trials.

PMID- 22382989
TI  - Pharmacokinetic and safety of raltegravir in pregnancy.

PMID- 22382990
TI  - A new synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK
      139), suppresses the Toll-like receptor 4-mediated inflammatory response through
      inhibition of the Akt/NF-kappaB pathway in BV2 microglial cells.
AB  - Microglial cells are the resident innate immune cells that sense pathogens and
      tissue injury in the central nervous system (CNS). Microglial activation is
      critical for neuroinflammatory responses. The synthetic compound 2-hydroxy
      3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this
      study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)
      mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited
      lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based
      assay. DK-139 blocked LPS-induced phosphorylation of IkappaB and p65/RelA NF
      kappaB, resulting in inhibition of the nuclear translocation and trans-acting
      activity of NF-kappaB in BV2 microglial cells. We also found that DK-139 reduced
      the expression of NF-kappaB target genes, such as those for COX-2, iNOS, and IL
      1beta, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS
      induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced
      phosphorylation of p65/RelA, while overexpression of dominant- active p110CAAX
      enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These
      results suggest that DK-139 exerts an anti-inflammatory effect on microglial
      cells by inhibiting the Akt/IkappaB kinase (IKK)/NF-kappaB signaling pathway.

PMID- 22382991
TI  - Automatic identification of activity-rest periods based on actigraphy.
AB  - We describe a novel algorithm for identification of activity/rest periods based
      on actigraphy signals designed to be used for a proper estimation of ambulatory
      blood pressure monitoring parameters. Automatic and accurate determination of
      activity/rest periods is critical in cardiovascular risk assessment applications
      including the evaluation of dipper versus non-dipper status. The algorithm is
      based on adaptive rank-order filters, rank-order decision logic, and
      morphological processing. The algorithm was validated on a database of 104
      subjects including actigraphy signals for both the dominant and non-dominant
      hands (i.e., 208 actigraphy recordings). The algorithm achieved a mean
      performance above 94.0%, with an average number of 0.02 invalid transitions per
      48 h.

PMID- 22382992
TI  - Ubiquitous urease affects soybean susceptibility to fungi.
AB  - The soybean ubiquitous urease (encoded by GmEu4) is responsible for recycling
      metabolically derived urea. Additional biological roles have been demonstrated
      for plant ureases, notably in toxicity to other organisms. However, urease
      enzymatic activity is not related to its toxicity. The role of GmEu4 in soybean
      susceptibility to fungi was investigated in this study. A differential expression
      pattern of GmEu4 was observed in susceptible and resistant genotypes of soybeans
      over the course of a Phakopsora pachyrhizi infection, especially 24 h after
      infection. Twenty-nine adult, transgenic soybean plants, representing six
      independently transformed lines, were obtained. Although the initial aim of this
      study was to overexpress GmEu4, the transgenic plants exhibited GmEu4 co
      suppression and decreased ureolytic activity. The growth of Rhizoctonia solani,
      Phomopsis sp., and Penicillium herguei in media containing a crude protein
      extract from either transgenic or non-transgenic leaves was evaluated. The fungal
      growth was higher in the protein extracts from transgenic urease-deprived plants
      than in extracts from non-transgenic controls. When infected by P. pachyrhizi
      uredospores, detached leaves of urease-deprived plants developed a significantly
      higher number of lesions, pustules and erupted pustules than leaves of non
      transgenic plants containing normal levels of the enzyme. The results of the
      present work show that the soybean plants were more susceptible to fungi in the
      absence of urease. It was not possible to overexpress active GmEu4. For future
      work, overexpression of urease fungitoxic peptides could be attempted as an
      alternative approach.

PMID- 22382993
TI  - Molecular cloning and functional characterization of a novel apple MdCIPK6L gene
      reveals its involvement in multiple abiotic stress tolerance in transgenic
      plants.
AB  - CBL-interacting protein kinases (CIPKs) are involved in many aspects of plant
      responses to abiotic stresses. However, their functions are poorly understood in
      fruit trees. In this study, a salt-induced MdCIPK6L gene was isolated from apple.
      Its expression was positively induced by abiotic stresses, stress-related
      hormones and exogenous Ca(2+). MdCIPK6L was not homologous to AtSOS2, however,
      its ectopic expression functionally complemented Arabidopsis sos2 mutant.
      Furthermore, yeast two-hybrid assay showed that MdCIPK6L protein interacted with
      AtSOS3, indicating that it functions in salt tolerance partially like AtSOS2
      through SOS pathway. As a result, the overexpression of both MdCIPK6L and
      MdCIPK6LT175D remarkably enhanced the tolerance to salt, osmotic/drought and
      chilling stresses, but did not affect root growth, in transgenic Arabidopsis and
      apple. Also, T-to-D mutation to MdCIPK6L at Thr175 did not affect its function.
      These differences between MdCIPK6L and other CIPKs, especially CIPK6s, indicate
      that MdCIPK6L encodes a novel CIPK in apple. Finally, MdCIPK6L overexpression
      also conferred tolerance to salt, drought and chilling stresses in transgenic
      tomatoes. Therefore, MdCIPK6L functions in stress tolerance crossing the species
      barriers, and is supposed to be a potential candidate gene to improve stress
      tolerance by genetic manipulation in apple and other crops.

PMID- 22382994
TI  - Role of environmental persistence in pathogen transmission: a mathematical
      modeling approach.
AB  - Although diseases such as influenza, tuberculosis and SARS are transmitted
      through an environmentally mediated mechanism, most modeling work on these topics
      is based on the concepts of infectious contact and direct transmission. In this
      paper we use a paradigm model to show that environmental transmission appears
      like direct transmission in the case where the pathogen persists little time in
      the environment. Furthermore, we formulate conditions for the validity of this
      modeling approximation and we illustrate them numerically for the cases of
      cholera and influenza. According to our results based on recently published
      parameter estimates, the direct transmission approximation fails for both cholera
      and influenza. While environmental transmission is typically chosen over direct
      transmission in modeling cholera, this is not the case for influenza.

PMID- 22382995
TI  - Locating pollutant emission sources with optical remote sensing measurements and
      an improved one-dimensional radial plume mapping technique.
AB  - Previous studies have shown that there was a relatively large amount of
      uncertainty along the major wind direction in the results of locating emission
      sources using the one-dimensional radial plume mapping (RPM(1D)) technique based
      on optical remote sensing measurements. This paper proposes setting up an
      additional monitoring line that is perpendicular to the original scanning beam
      geometry to reduce this uncertainty. We first conducted a computer simulation
      study using the Gaussian dispersion model to generate the downwind concentrations
      of plumes from 400 source locations in a 201 m * 201 m spatial domain under
      various wind directions (n = 181). The optical remote sensing instrument was
      assumed to be at (0, 0) with two perpendicular monitoring lines, each of which
      had three beam segments of equal length. Each pair of the reconstructed downwind
      concentration profiles was then used to trace back to the source locations. The
      results showed that the accuracy of the method and its uncertainty were improved
      by using the proposed two-line RPM(1D) approach rather than the original one-line
      RPM(1D) approach at most simulated source locations. In a follow-up field
      experiment, a tracer gas was released at the coordinate of (100, 100). The
      release location was covered within the 0.25- to 0.5-probability area of the
      estimated results, and the distance between the actual and estimated source
      locations was 18.4 m (9.2% of the longest beam path).

PMID- 22382996
TI  - Models of neurological disease (substance abuse): self-administration in monkeys.
AB  - Drug self-administration is a procedure in which a subject performs a specified
      response that results in the delivery of a drug injection. This procedure is
      viewed as a relevant model for the study of human drug-taking behavior. Drug self
      administration in primates has several characteristics that resemble drug-taking
      behavior in humans, and agents commonly abused by humans also generally maintain
      self-administration behavior in monkeys. Self-administration procedures allow for
      the study of a variety of drug properties. For instance, they can be used to
      investigate the abuse potential of new compounds and to study the effects of
      candidate medications for the treatment of drug addiction. These procedures can
      also be employed for examining drug reinforcement mechanisms. Described in this
      unit are procedures for studying intravenous drug self-administration in large
      primates, such as rhesus macaques, and smaller primates, such as squirrel
      monkeys.

PMID- 22382997
TI  - Measurement of cell death in Mammalian cells.
AB  - Methods for assessing mammalian cell death are presented in this unit. The unit
      is divided into six sections: (1) a brief overview of cytotoxicity and pathways
      of cell death, (2) a method to measure cell death using lactate dehydrogenase
      (LDH) release as a marker of membrane integrity, (3) a flow cytometry method that
      simultaneously measures two types of cell death, necrosis, and apoptosis, (4) use
      of fluorescence microscopy and nuclear morphology to assess apoptosis and
      necrosis, (5) the use of multi-well plates and high-content analysis imaging
      systems to assess nuclear morphology, and (6) a discussion of the use of
      cytotoxicity assays to determine the mechanisms of cell death.

PMID- 22382998
TI  - Evaluating modulators of "Regulator of G-protein Signaling" (RGS) proteins.
AB  - "Regulator of G-protein Signaling" (RGS) proteins constitute a class of
      intracellular signaling regulators that accelerate GTP hydrolysis by
      heterotrimeric Galpha subunits. In recent years, RGS proteins have emerged as
      potential drug targets for modulation by small molecules. Described in this unit
      are high-throughput screening procedures for identifying modulators of RGS
      protein-mediated GTPase acceleration (GAP activity), for assessment of RGS
      domain/Galpha interactions (most avid in vitro when Galpha is bound by aluminum
      tetrafluoride), and for validation of candidate GAP-modulatory molecules with the
      single-turnover GTP hydrolysis assay.

PMID- 22382999
TI  - Models of inflammation: Carrageenan- or complete Freund's Adjuvant (CFA)-induced
      edema and hypersensitivity in the rat.
AB  - Animal models of inflammation are used to assess the production of inflammatory
      mediators at sites of inflammation, the anti-inflammatory properties of agents
      such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of
      putative analgesic compounds in reversing cutaneous hypersensitivity. This unit
      details methods to elicit and measure carrageenan- and complete Freund's adjuvant
      (CFA)-induced cutaneous inflammation. Due to possible differences between the
      dorsal root sensory system and the trigeminal sensory system, injections of
      either the footpad or vibrissal pad are described. In this manner, cutaneous
      inflammation can be assessed in tissue innervated by the lumbar dorsal root
      ganglion neurons (footpad) and by the trigeminal ganglion neurons (vibrissal
      pad).

PMID- 22383000
TI  - Models of inflammation: carrageenan air pouch.
AB  - The subcutaneous air pouch is an in vivo model that can be used to study acute
      and chronic inflammation, the resolution of the inflammatory response, and the
      oxidative stress response. Injection of irritants into an air pouch in rats or
      mice induces an inflammatory response that can be quantified by the volume of
      exudate produced, the infiltration of cells, and the release of inflammatory
      mediators. The model presented in this unit has been extensively used to identify
      potential anti-inflammatory drugs.

PMID- 22383015
TI  - State and trait anxiety levels of adolescents in a changing society, Kirikkale
      city, Turkey.
AB  - Adolescents face rapidly changing challenges. Psychosocial health problems during
      adolescence are relatively common in all cultures. This study was designed to
      evaluate the state and trait anxiety status and influencing sociodemographic and
      other factors, thought to pertain to youth, on anxiety among school children in
      Kirikkale. It was carried out at three public primary and two high schools
      representative of two different socioeconomic statuses. 430 Turkish school
      children (246 girls, 184 boys) were asked voluntarily to answer a set of
      questionnaires in their classrooms at the beginning of a training programme. Then
      the State and Trait Anxiety Inventory for Children was administered. Mean age of
      the students was 14.16 +/- 1.87 years. The mean total STAI-CS and STAI-CT scores
      were 40.24 +/- 11.64, and 44.71 +/- 9.64, respectively. There were no differences
      in STAI-CS and STAI-CT scores between boys and girls in both schools and in all
      age groups. Among girls, a positive body image had a significant effect on state
      anxiety scores. There was a positive correlation between age and anxiety scores
      (r = .17, F:12.176, p < .001). Students identifying their families SES as bad
      and/or moderate scored significantly higher in comparison to the other groups (p
      < .05). STAI-CS scores were higher for lower educational grade, higher body
      weight and sleep problems. In Kirikkale, a city faced with substantial changes in
      cultural and traditional norms, adolescents could be expected to be under stress
      and appear to be responding to stress with anxiety.

PMID- 22383016
TI  - Implementation of primary care-mental health integration services in the Veterans
      Health Administration: program activity and associations with engagement in
      specialty mental health services.
AB  - This paper describes the status of the Veterans Health Administration (VHA)
      Primary Care-Mental Health Integration (PC-MHI) services implementation and
      presents an assessment of associations between receipt of PC-MHI services and
      likelihood of receiving a second specialty mental health (SMH) appointment
      following an initial SMH encounter. The total PC-MHI service recipients and
      encounters/month rose substantially between October 2007 and April 2011.
      Adjusting for important covariates, the likelihood of receiving a second SMH
      encounter within 3 months of an index SMH appointment was 1.37 times greater
      among individuals who had received a PC-MHI encounter within 3 months of the
      initial SMH appointment. Implementation of VHA PC-MHI services has substantially
      increased VHA capacity to deliver mental health services in primary care and
      findings indicate that PC-MHI services are associated with greater engagement in
      SMH treatment. Implementation of VHA PC-MHI services is progressing with new
      technical assistance strategies being deployed.

PMID- 22383017
TI  - Make the context work for you: faculty in a changing academic medicine landscape.
AB  - Academic medicine's landscape is dynamically adjusting. The changes are
      accelerating and these alterations are impacting both the faculty workforce as a
      whole and individual faculty members. This article reviews workforce and
      institutional changes within academic medicine and supports the need for faculty
      members to adapt to this changing landscape. Resources to maintain an
      understanding of these ongoing changes are reviewed. A faculty life-cycle model
      is proposed as a context for developing a personal action plan. Career management
      steps are suggested to facilitate career productivity and satisfaction. Finally,
      we propose that psychologists, being human behavior experts, are well positioned
      to contribute within the transformation of academic medicine.

PMID- 22383019
TI  - High rate of ceramic sandwich liner fracture.
AB  - BACKGROUND: Ceramic bearing surfaces for THA were introduced to reduce the risk
      of wear. However, owing to liner fracture in some of the early series and
      presumption that the fractures were the result of the modulus mismatch of the
      implant and the bone, a ceramic sandwich liner with lower structural rigidity was
      introduced. Fractures of these devices also were reported subsequently, although
      the incidence is unclear and it is unknown whether there are any risk factors
      associated with the fractures. QUESTIONS/PURPOSES: We therefore determined the
      incidence of these fractures. METHODS: We retrospectively reviewed 298 active
      patients in whom we implanted 353 ceramic-polyethylene sandwich liner acetabular
      components between November 1999 and February 2008. The mean age of the patients
      was 53.6 years (range, 17-84 years). The minimum followup was 6 months (mean, 41
      months; range, 6-106 months). All patients were assessed clinically and
      radiographically. RESULTS: Seven of the 353 (2%) ceramic sandwich liners
      fractured at a mean of 4.3 years (range, 1.3-7.6 years) after surgery without
      trauma. Neither patient-related factors nor radiographic position of the implants
      were risk factors for fracture. CONCLUSIONS: Owing to the high rate of fractures
      of the sandwich ceramic polyethylene liners in our patients, we have discontinued
      use of this device. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 22383018
TI  - Integrating pain management in clinical practice.
AB  - There is much evidence to suggest that psychological and social issues are
      predictive of pain severity, emotional distress, work disability, and response to
      medical treatments among persons with chronic pain. Psychologists can play an
      important role in the identification of psychological and social dysfunction and
      in matching personal characteristics to effective interventions as part of a
      multidisciplinary approach to pain management, leading to a greater likelihood of
      treatment success. The assessment of different domains using semi-structured
      clinical interviews and standardized self-report measures permits identification
      of somatosensory, emotional, cognitive, behavioral and social issues in order to
      facilitate treatment planning. In this paper, we briefly describe measures to
      assess constructs related to pain and intervention strategies for the behavioral
      treatment of chronic pain and discuss related psychiatric and substance abuse
      issues. Finally, we offer a future look at the role of integrating pain
      management in clinical practice in the psychological assessment and treatment for
      persons with chronic pain.

PMID- 22383020
TI  - Is application of an internal anterior pelvic fixator anatomically feasible?
AB  - BACKGROUND: Spinal hardware has been adapted for fixation in the setting of
      anterior pelvic injury. This anterior subcutaneous pelvic fixator consists of
      pedicle screws placed in the supraacetabular region connected by a contoured
      connecting rod placed subcutaneously and above the abdominal muscle fascia.
      QUESTIONS/PURPOSES: We examined the placement of the components for anterior
      subcutaneous pelvic fixator relative to key vascular, urologic, bony, and surface
      structures. METHODS: We measured the CT scans of 13 patients after placement of
      the pelvic fixator to determine the shortest distances between the fixator
      components and important anatomic structures: the femoral vascular bundle, the
      urinary bladder, the cranial margin of the hip, the screw insertion point on the
      bony pelvis, the relationship between the pedicle screw and the corridor of bone
      in which it resided, and the position relative to the skin. RESULTS: The average
      distance from the vascular bundle to the pedicle screw was 4.1 cm and 2.2 cm to
      the connecting rod. The average distance from the connecting rod to the anterior
      edge of the bladder was 2.6 cm. The average distance from the screw insertion
      point to the hip was 2.4 cm; none penetrated the hip. The average screw was in
      bone for 5.9 cm. The pedicle screws were on average 2.1 cm under the skin. The
      average distance from the anterior skin to the connecting rod was 2.7 cm.
      CONCLUSIONS: Components of this anterior pelvic fixator are close to important
      anatomic structures. Careful adherence to the surgical technique should minimize
      potential risk. LEVEL OF EVIDENCE: Level IV, retrospective study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 22383021
TI  - Biographical sketch: William John Little, FRCS (1810-1894).
AB  - This biographical sketch on William Little corresponds to the historic text, The
      Classic: Hospital for the Cure of Deformities: Course of Lectures on the
      Deformities of the Human Frame (1843), available at DOI 10.1007/s11999-012-2302-y
      .

PMID- 22383022
TI  - Improved thermal stability of oxide-supported naked gold nanoparticles by ligand
      assisted pinning.
AB  - We report a method to improve the thermal stability, up to 900  degrees C, of
      bare-metal (naked) gold nanoparticles supported on top of SiO(2) and SrTiO(3)
      substrates via ligand-assisted pinning. This approach leads to monodisperse naked
      gold nanoparticles without significant sintering after thermal annealing in air
      at 900  degrees C. The ligand-assisted pinning mechanism is described.

PMID- 22383023
TI  - Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for
      patients with unresectable liver-only metastases from colorectal cancer in Japan:
      ROOF study.
AB  - BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases
      can reduce tumor size, which sometimes leads to curative resection. The aim of
      the present study was to identify and describe patients with initially
      unresectable liver-only metastases from colorectal cancer who obtained sufficient
      chemotherapeutic benefit that eventually lead to the removal of the metastatic
      diseases in the liver. METHODS: A phase II multicenter cooperative study was
      conducted in 38 medical institutions using modified FOLFOX6 (mFOLFOX6) as
      neoadjuvant chemotherapy from January 2008 to June 2009. Patients with liver-only
      metastases from colorectal cancer that was deemed not optimally resectable by
      liver surgeons received mFOLFOX6 as preoperative neoadjuvant chemotherapy for 6-8
      cycles. Patients were reassessed for resectability after 6 cycles of mFOLFOX6.
      Surgery was carried out 3-6 weeks after chemotherapy. The primary endpoint was
      the rate of macroscopic curative surgery including liver resection. RESULTS: 36
      patients (23 male/13 female, ECOG performance status 0-1) were enrolled. The
      median age of the patients was 62.5 years; 78% (28 patients) had 5 or more
      metastatic tumors, and 50% (18 patients) had metastatic tumors over 5 cm
      diameter. The mFOLFOX6 regimen was safety administered resulting in 18 partial
      responses (50%), 12 stable disease, and 4 progressive disease. There was no grade
      3/4 neurotoxicity. Fourteen patients (38.9%) underwent surgery (R0: 13; R1: 1).
      Of these, thirteen patients (36.1%) underwent R0 surgery. CONCLUSIONS: Our data
      suggest that mFOLFOX6 has a high response rate in patients with liver-only
      metastases from colorectal cancer, allowing for R0 resection of liver metastases
      in a proportion of patients initially not judged to be optimally resectable.

PMID- 22383024
TI  - Successful treatment of infants with localized neuroblastoma based on their MYCN
      status.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of post
      surgical chemotherapy for infants with localized neuroblastoma without MYCN
      amplification (MNA), and determine whether risk classification using MNA is
      reasonable. METHODS: Four hundred and fourteen eligible patients were registered
      between 1998 and 2004. Resectable patients in stage 1 and 2A/2B were treated by
      surgical resection only. Unresectable patients in stage 3 without MNA received
      either 6 cycles of regimen A or 3 cycles of regimen A plus 3 cycles of regimen
      C2; regimen A consisted of low doses of cyclophosphamide and vincristine and
      regimen C consisted of cyclophosphamide, vincristine and pirarubicin before
      surgical resection. The resectable and unresectable patients were randomly
      selected to receive post-surgical chemotherapy. The patients with MNA received
      intensive chemotherapy regimen D2, consisting of cyclophosphamide, vincristine,
      pirarubicin and cisplatin, and some of them received high-dose chemotherapy with
      stem cell transplantation. RESULTS: The 5-year event-free survival (5-EFS) rates
      of stage 1 and 2A/2B patients without MNA were 97.2 and 89.0% respectively (p =
      0.02). A total of 31 patients in stage 3 without MNA received post-surgical
      chemotherapy, and 30 patients did not. The 5-EFS rates of these two groups (96.0
      and 96.2%, respectively) were not significantly different (p = 0.869). The 5-EFS
      rate for localized patients with MNA (n = 6) was 50.0%, and that of patients
      without MNA was 95.0% (p < 0.001). CONCLUSION: Post-surgical chemotherapy was
      therefore unnecessary for localized patients without MNA. This treatment strategy
      using MNA is considered to be appropriate in infants.

PMID- 22383025
TI  - Attributes of brain metastases from breast and lung cancer.
AB  - BACKGROUND: Most brain metastases arise from breast and lung cancers. Few studies
      compare the brain regions they involve, their numbers and intrinsic attributes.
      METHODS: Records of all patients referred to Radiation Oncology for treatment of
      symptomatic brain metastases were obtained. Computed tomography (n = 56) or
      magnetic resonance imaging (n = 72) brain scans were reviewed. RESULTS: Data from
      68 breast and 62 lung cancer patients were compared. Brain metastases presented
      earlier in the course of the lung than of the breast cancer patients (p = 0.001).
      There were more metastases in the cerebral hemispheres of the breast than of the
      lung cancer patients (p = 0.014). More breast than lung cancer patients had
      cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases
      and presence of cerebellar metastases were positively correlated (p = 0.001). The
      prevalence of at least one metastasis surrounded with >2 cm of edema was greater
      for the lung than for the breast patients (p = 0.019). The primary tumor type,
      rather than the scanning method, correlated with differences between these
      variables. CONCLUSIONS: Brain metastases from lung occur earlier, are more
      edematous, but fewer in number than those from breast cancers. Cerebellar brain
      metastases are more frequent in breast cancer.

PMID- 22383027
TI  - Binding of autoantibodies to the core region of tissue transglutaminase is a
      feature of paediatric coeliac disease.
AB  - OBJECTIVES: Production of autoantibodies to the enzyme tissue transglutaminase
      (tTG) is a hallmark of coeliac disease (CD). We have previously demonstrated that
      the immumoglobulin (Ig) A response to tTG in adult CD specifically targets its
      catalytic core region, containing the active-site triad of amino acids. The aim
      of the present study was to investigate this phenomenon in paediatric patients
      with CD, and to elucidate the contribution of each active-site residue to
      epitopes recognised. The specificity of the IgG anti-tTG response was also
      investigated and compared with that of the IgA anti-tTG response, in both
      paediatric and adult patients with CD. METHODS: Wild-type and novel variants of
      tTG were generated via site-directed mutagenesis and expressed as glutathione-S
      transferase-fusion proteins in Escherichia coli BL-21. The mutagenic variants of
      tTG had substitutions of 1, 1, or all of the 3 of the catalytic triad amino
      acids. All of the recombinant tTGs were tested for their antigenicity in IgA and
      IgG enzyme-linked immunosorbent assays with cohorts of paediatric (n=63) and
      adult (n=30) CD sera. RESULTS: Substitution of even 1 amino acid in the catalytic
      triad resulted in a significant reduction of CD IgA and IgG anti-tTG binding,
      with all of the mutant proteins displaying diminished antigenicity compared with
      the wild-type protein. CONCLUSIONS: The core region of tTG is specifically
      targeted from early on in disease course by CD patient autoantibodies of both the
      IgA and IgG class.

PMID- 22383026
TI  - Bifidobacteria isolated from infants and cultured on human milk oligosaccharides
      affect intestinal epithelial function.
AB  - OBJECTIVES: Human milk oligosaccharides (HMOs) are the third most abundant
      component of breast milk. Our laboratory has previously revealed gene clusters
      specifically linked to HMO metabolism in selected bifidobacteria isolated from
      fecal samples of infants. Our objective was to test the hypothesis that growth of
      selected bifidobacteria on HMO stimulates the intestinal epithelium. METHODS:
      Caco-2 and HT-29 cells were incubated with lactose (LAC)- or HMO-grown
      Bifidobacterium longum subsp infantis (B infantis) or B bifidum. Bacterial
      adhesion and translocation were measured by real-time quantitative polymerase
      chain reaction. Expression of pro- and anti-inflammatory cytokines and tight
      junction proteins was analyzed by real-time reverse transcriptase. Distribution
      of tight junction proteins was measured using immunofluorescent microscopy.
      RESULTS: We showed that HMO-grown B infantis had a significantly higher rate of
      adhesion to HT-29 cells compared with B bifidum. B infantis also induced
      expression of a cell membrane glycoprotein, P-selectin glycoprotein ligand-1.
      Both B infantis and B bifidum grown on HMO caused less occludin relocalization
      and higher expression of anti-inflammatory cytokine, interleukin-10 compared with
      LAC-grown bacteria in Caco-2 cells. B bifidum grown on HMO showed higher
      expression of junctional adhesion molecule and occludin in Caco-2 cells and HT-29
      cells. There were no significant differences between LAC or HMO treatments in
      bacterial translocation. CONCLUSIONS: The study provides evidence for the
      specific relation between HMO-grown bifidobacteria and intestinal epithelial
      cells. To our knowledge, this is the first study describing HMO-induced changes
      in the bifidobacteria-intestinal cells interaction.

PMID- 22383028
TI  - Challenge of measuring how much gluten is too much.

PMID- 22383029
TI  - Food questionnaire for the assessment of gluten intake by children 1 to 4 years
      old.
AB  - OBJECTIVES: A food questionnaire (FQ) to assess gluten intake in infants 0 to 12
      months old has been developed and validated (FQ-gluten), but an instrument to
      assess gluten intake in children 1 to 4 years is not available. Development and
      validation of such an instrument (FQ-gluten4) was the aim of the present study.
      METHODS: The FQ-gluten was adapted according to age-related food consumption. The
      results of this FQ-gluten4 were compared with the results of a 2-day food record.
      RESULTS: Seventy-one parents filled in both instruments. The mean amount of
      gluten consumption calculated from the FQ-gluten4 was comparable with that of the
      food record, but significant differences were found in the amount of gluten
      intake in 1- to 2-year-old children and in the percentage of gluten from porridge
      among the 1- to 3-year-olds. The Blant-Altman limits of agreement with standard
      deviation of 2600 mg were -5118 to 5630 mg. CONCLUSIONS: The new, short,
      standardized, validated, and easy-to-use FQ-gluten4 may be a useful instrument in
      the assessment of gluten intake in young children. Using this standardized method
      provides opportunity for better comparison of the results of gluten consumption
      in studies throughout the world. Furthermore, such an instrument can be used to
      quantify the gluten intake in individuals suspected to have celiac disease but in
      whom the diagnoses cannot be confirmed.

PMID- 22383030
TI  - Characteristics of intestinal habits in children younger than 4 years:  detecting
      constipation.
AB  - OBJECTIVES: The aim of the present study was to describe the prevalence of
      childhood constipation, stool characteristics, and their relationship with toilet
      training and age of introduction of cow's milk. METHODS: A total of 4231 children
      born in 2004, from a birth cohort study, were assessed at 12, 24, and 48 months
      of age, when their mothers provided information on sociodemographic
      characteristics, bowel habits, toilet training, and age of introduction of cow's
      milk and other foods. RESULTS: The prevalence of constipation was 27.3% and 31.0%
      at 24 and 48 months of age, respectively. Among girls, at 48 months of age, it
      was 34.4% versus 27.4% in boys (P<0.001). The most common features of
      constipation were scybalous stools (47.7% and 41.0% at 24 and 48 months,
      respectively), evacuation difficulty (24.3% and 23.1%), and hard stools (17.8%
      and 34.1%). Toilet training starting before 24 months was associated with
      constipation at 24 months and its persistence up to 48 months. Among children who
      did not receive cow's milk in their first year of life, 22% had constipation at
      24 months, 22.6% at 48 months, and 8.3% at 24 and 48 months. Among children who
      started cow's milk before 30 days of life, the respective proportions of children
      with constipation was 28.2%, 33%, and 12.4%. CONCLUSIONS: The prevalence of
      constipation increases with age and cannot be detected using only information on
      evacuation interval. Toilet training before 24 months and introduction of cow's
      milk before 1 year of age is positively associated with constipation at 24 months
      and its persistence up to 48 months.

PMID- 22383031
TI  - The adipofascial flap based on an ulnar artery perforator: an alternative option
      for recurrent carpal tunnel syndrome.

PMID- 22383032
TI  - Radial nerve palsy with hourglass-like constrictions in a child.

PMID- 22383033
TI  - Designer tridentate mucin 1 aptamer for targeted drug delivery.
AB  - A single-stranded DNA aptamer (APT) capable of targeting mucin 1 (MUC1)
      extracellular protein was modified to increase its drug delivery specificity
      toward MUC1 overexpressing cancer cell line, MCF7. The active targeting region of
      APT was truncated and variable repeats (one, two, or three) of this sequence were
      synthesized. An aptamer formed from three repeats of this active targeting region
      (L3) was shown to possess enhanced doxorubicin (DOX) intercalation ability, and
      L3-DOX complex exhibited selective cytotoxicity to MCF7 over RAW cells. Most
      importantly, L3 was able to evade RAW 264.7 macrophages (2-fold reduction in L3
      uptake relative to APT), thus resulting in an overall 5.5-fold increase of
      survivability of RAW cells as compared with when free DOX was used. These results
      indicate that aptamer L3 has good potential for targeted drug therapeutics.

PMID- 22383035
TI  - Diagnosis and management of the multiligament-injured knee.
AB  - Knee injuries involving multiple ligaments, which are often associated with
      tibiofemoral joint dislocations, are complex injuries that are challenging to
      evaluate and treat. The clinician must have a thorough understanding of knee
      anatomy and be capable of a detailed physical examination to determine the extent
      and pattern of injury. Accurate interpretation of imaging studies is crucial but
      cannot replace the physical examination. The magnitude of deforming forces and
      amount of translation and rotation of the tibia in relation to the femur
      determine the risk for neurovascular injury. Most patients with multiligament
      knee injuries undergo surgical management; however, some patients may be best
      served by a nonoperative approach. Successful rehabilitation consists of
      achieving good range of motion and strength, as well as normal gait mechanics,
      while respecting the stages of healing.

PMID- 22383036
TI  - Differential gene and transcript expression analysis of RNA-seq experiments with
      TopHat and Cufflinks.
AB  - Recent advances in high-throughput cDNA sequencing (RNA-seq) can reveal new genes
      and splice variants and quantify expression genome-wide in a single assay. The
      volume and complexity of data from RNA-seq experiments necessitate scalable, fast
      and mathematically principled analysis software. TopHat and Cufflinks are free,
      open-source software tools for gene discovery and comprehensive expression
      analysis of high-throughput mRNA sequencing (RNA-seq) data. Together, they allow
      biologists to identify new genes and new splice variants of known ones, as well
      as compare gene and transcript expression under two or more conditions. This
      protocol describes in detail how to use TopHat and Cufflinks to perform such
      analyses. It also covers several accessory tools and utilities that aid in
      managing data, including CummeRbund, a tool for visualizing RNA-seq analysis
      results. Although the procedure assumes basic informatics skills, these tools
      assume little to no background with RNA-seq analysis and are meant for novices
      and experts alike. The protocol begins with raw sequencing reads and produces a
      transcriptome assembly, lists of differentially expressed and regulated genes and
      transcripts, and publication-quality visualizations of analysis results. The
      protocol's execution time depends on the volume of transcriptome sequencing data
      and available computing resources but takes less than 1 d of computer time for
      typical experiments and ~1 h of hands-on time.

PMID- 22383037
TI  - Creating interactive, web-based and data-enriched maps with the Systems Biology
      Graphical Notation.
AB  - The Systems Biology Graphical Notation (SBGN) is an emerging standard for the
      uniform representation of biological processes and networks. By using examples
      from gene regulation and metabolism, this protocol shows the construction of SBGN
      maps by either manual drawing or automatic translation using the tool SBGN-ED. In
      addition, it discusses the enrichment of SBGN maps with different kinds of -omics
      data to bring numerical data into the context of these networks in order to
      facilitate the interpretation of experimental data. Finally, the export of such
      maps to public websites, including clickable images, supports the communication
      of results within the scientific community. With regard to the described
      functionalities, other tools partially overlap with SBGN-ED. However, currently,
      SBGN-ED is the only tool that combines all of these functions, including the
      representation in SBGN, data mapping and website export. This protocol aims to
      assist scientists with the step-by-step procedure, which altogether takes ~90
      min.

PMID- 22383038
TI  - Monitoring the spatiotemporal dynamics of proteins at replication forks and in
      assembled chromatin using isolation of proteins on nascent DNA.
AB  - Understanding the processes of DNA replication, chromatin assembly and
      maturation, and the replication stress response requires the ability to monitor
      protein dynamics at active and damaged replication forks. Detecting protein
      accumulation at replication forks or damaged sites has primarily relied on
      immunofluorescence imaging, which is limited in resolution and antibody
      sensitivity. Here we describe a procedure to isolate proteins on nascent DNA
      (iPOND) that permits a high-resolution spatiotemporal analysis of proteins at
      replication forks or on chromatin following DNA replication in cultured cells.
      iPOND relies on labeling of nascent DNA with the nucleoside analog 5-ethynyl-2'
      deoxyuridine (EdU). Biotin conjugation to EdU-labeled DNA using click chemistry
      facilitates a single-step streptavidin purification of proteins bound to the
      nascent DNA. iPOND permits an interrogation of any cellular process linked to DNA
      synthesis using a 3- to 4-d protocol.

PMID- 22383039
TI  - Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice.
AB  - Exposure of humans and rodents to cold activates thermogenic activity in brown
      adipose tissue (BAT). This protocol describes a mouse model to study the
      activation of BAT and angiogenesis in adipose tissues by cold acclimation. After
      a 1-week exposure to 4  degrees C, adult C57BL/6 mice show an obvious transition
      from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue
      (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the
      end of week 5 BRITE contains a high number of uncoupling protein-1-positive
      mitochondria, a characteristic feature of BAT. During the transition from WAT
      into BRITE, the vascular density is markedly increased owing to the activation of
      angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the
      mitochondrial content and metabolic rate. BAT and the increased metabolic rate
      result in a lean phenotype. This protocol provides an outstanding opportunity to
      study the molecular mechanisms that control adipose mass.

PMID- 22383040
TI  - A novel approach to rapid detection of acute water toxicity and its policy
      implications for grassroots sustainable environmental monitoring.
AB  - Unknown chemicals, emerging contaminants, and the resulting reactions among them
      make early detection and warning of acute water toxicity extremely challenging.
      The conventional approach using small fish for toxicity monitoring normally
      requires a designated species of fish and over a week's time to complete,
      including dilution of the wastewater, a pre-test, and a full test. It often
      increases chances for error and delays emergency management. This paper reports a
      novel approach, based on grassroots knowledge and field and lab experience in
      Jilin, China. This approach uses a combination of different species of aquarium
      fish to achieve fast and reliable monitoring. It tests the original source water
      directly without going through the dilution procedure, while paying attention to
      the time factor. The approach does not require a pre-test and may shorten the
      time needed for detecting acute toxicity to a few minutes, using a new
      classification of aquatic toxicity levels. It is inexpensive to use and may be
      easily adopted by grassroots organizations. The approach is "greener" and more
      financially and socially sustainable than traditional approaches. The wide use of
      the approach has the potential to encourage policy innovations for making
      toxicity monitoring grassroots based and more effective in reducing acute
      contamination emergencies.

PMID- 22383041
TI  - Pyramidal neurons in the superficial layers of rat retrosplenial cortex exhibit a
      late-spiking firing property.
AB  - The rodent granular retrosplenial cortex (GRS) is reciprocally connected with the
      hippocampus. It is part of several networks implicated in spatial learning and
      memory, and is known to contain head-direction cells. There are, however, few
      specifics concerning the mechanisms and microcircuitry underlying its involvement
      in spatial and mnemonic functions. In this report, we set out to characterize
      intrinsic properties of a distinctive population of small pyramidal neurons in
      layer 2 of rat GRS. These neurons, as well as those in adjoining layer 3, were
      found to exhibit a late-spiking (LS) firing property. We established by multiple
      criteria that the LS property is a consequence of delayed rectifier and A-type
      potassium channels. These were identified as Kv1.1, Kv1.4 and Kv4.3 by Genechip
      analysis, in situ hybridization, single-cell reverse transcriptase-polymerase
      chain reaction, and pharmacological blockade. The LS property might facilitate
      comparison or integration of synaptic inputs during an interval delay, consistent
      with the proposed role of the GRS in memory-related processes.

PMID- 22383043
TI  - Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer
      microelectrodes for transmitter detection.
AB  - In this paper we investigate the physical and electrochemical properties of
      micropatterned poly(3,4-ethylenedioxythiophene):tosylate (PEDOT:tosylate)
      microelectrodes for neurochemical detection. PEDOT:tosylate is a promising
      conductive polymer electrode material for chip-based bioanalytical applications
      such as capillary electrophoresis, high-performance liquid chromatography, and
      constant potential amperometry at living cells. Band electrodes with widths down
      to 3 MUm were fabricated on polymer substrates using UV lithographic methods. The
      electrodes are electrochemically stable in a range between -200 mV and 700 mV vs.
      Ag/AgCl and show a relatively low resistance. A wide range of transmitters is
      shown to oxidize readily on the electrodes. Kinetic rate constants and half wave
      potentials are reported. The capacitance per area was found to be high (1670 +/-
      130 MUF cm(-2)) compared to other thin film microelectrode materials. Finally, we
      use constant potential amperometry to measure the release of transmitters from a
      group of PC 12 cells. The results show how the current response decreases for a
      series of stimulations with high K(+) buffer.

PMID- 22383042
TI  - Interleukin-7 and immune reconstitution in cancer patients: a new paradigm for
      dramatically increasing overall survival.
AB  - Although great effort is being expended in the development of cancer
      immunotherapies, it is surprising that global lymphopenia and its various
      dimensions are not being systematically assessed in cancer patients. The incident
      pathologies associated with various immunosuppressed conditions such as those
      found in HIV infection have taught us that measuring various T cell populations
      including CD4 provides the clinician with a reliable measure for gauging the risk
      of cancer and opportunistic infections. Importantly, recent data emphasize the
      key link between lymphocyte T cell counts and overall survival in cancer patients
      receiving chemotherapy. Treatment of immunocompromised patients with interleukin
      7 (IL-7), a critical growth and homeostatic factor for T cells, has been shown to
      produce a compelling profile of T cell reconstitution. The clinical results of
      this investigational therapy confirm data obtained from numerous preclinical
      studies and demonstrate the long-term stability of this immune reconstitution,
      not only on CD4 but also on CD8 T cells, involving recent thymic emigrants as
      well as naive, memory, and central memory T cells. Furthermore, IL-7 therapy also
      contributes to restoration of a broadened diversity of the T cell repertoire as
      well as to migration of these cells to lymph nodes and tissues. All these
      properties support the initiation of new clinical studies aimed at reconstituting
      the immune system of cancer patients before or immediately after chemotherapy in
      order to demonstrate a potentially profound increase in overall survival.

PMID- 22383044
TI  - Downregulation of the taurine transporter TauT during hypo-osmotic stress in
      NIH3T3 mouse fibroblasts.
AB  - The present work was initiated to investigate regulation of the taurine
      transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive
      enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and
      long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is
      reduced following reduction in osmolarity, keeping the extracellular Na(+)
      concentration constant. TonEBP activity is unaltered, whereas TauT transcription
      as well as TauT activity are significantly reduced under hypo-osmotic conditions.
      In contrast, TonEBP activity and TauT transcription are significantly increased
      following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3
      fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous
      application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP
      activity and taurine influx are regulated negatively by ROS under hypo-osmotic,
      low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure
      to ROS reduces taurine uptake as a result of modulated TauT transport kinetics.
      Thus, swelling-induced ROS production could account for the reduced taurine
      uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.

PMID- 22383045
TI  - Effect of simultaneously replacing putative TM6 and TM12 of human NBCe1-A with
      those from NBCn1 on surface abundance in Xenopus oocytes.
AB  - HCO3- translocation across the plasma membrane via the electrogenic Na/HCO3-
      cotransporter NBCe1 plays an important role in intracellular pH regulation and
      transepithelial HCO3- transport. However, the structural determinants of
      transporter function remain largely unknown. A previous study showed that the
      putative fourth extracellular loop (EL4) plays an essential role in determining
      the electrogenicity of NBCe1. In the present study, we generated eight new
      chimeras of human NBCe1-A and NBCn1-A. All possess the putative NBCe1 EL4 and are
      electrogenic. Chimera O, in which the putative sixth transmembrane segment (TM6)
      and EL5 through the C terminus (Ct) of NBCe1 was replaced by corresponding NBCn1
      sequence, produces the smallest hyperpolarization (1-2 mV) when CO2/HCO3- is
      added to the extracellular solution. Biotinylation experiments show that O has a
      very low abundance at the plasma membrane. However, chimeras in which we
      simultaneously replaced the putative TM6 and smaller subdomains of the EL5-Ct
      region for the NBCn1 sequence were strongly electrogenic except for chimera T, in
      which we replaced TM6 and TM12 of NBCe1 with the corresponding regions of NBCn1.
      T exhibited greatly reduced transporter surface expression compared to wild-type
      NBCe1-A, while retaining at least some electrogenic character. We hypothesize
      that putative TM6 and TM12 are part of a functional unit and that if the two TMs
      are replaced by those of the same transporter type, high surface expression would
      require that the surrounding TMs are also from the same transporter type.

PMID- 22383046
TI  - Improving psychotherapeutic medication prescribing in Florida: implementation of
      the Florida Medicaid Drug Therapy Management Program (MDTMP).
AB  - This paper describes a program that was established by Florida Medicaid to
      improve the quality of prescribing of psychotherapeutic medications. It relates
      the process used for defining quality medication treatment including the
      definitions of unusual psychotherapeutic medication indicators (UPMI). It details
      the results of analysis of FY 2007-2008 pharmacy claims data using these
      indicators that enabled the Program to identify practices and prescribers that
      required targeted interventions. The most frequently triggered UPMI for adults
      involved the use of 2 or more antipsychotics for greater than 60 days; high doses
      of psychotherapeutic medications was the indicator most frequently triggered for
      children closely followed by the use of 2 or more antipsychotics for more than 45
      days. Prescriptions that triggered UPMI were concentrated in a small number of
      prescribers. These results led to the Program focusing on these high frequency
      practices and on the prescribers most associated with them. They also led to the
      implementation of new quality improvement initiatives like the implementation of
      a psychiatric telephone consultation line for pediatricians who are treating
      children with serious emotional disturbances who do not have access to child
      psychiatrists.

PMID- 22383048
TI  - Aerobic granulation: advances and challenges.
AB  - Aerobic granulation was developed in overcoming the problem of biomass washout
      often encountered in activated sludge processes. The novel approach to developing
      fluffy biosolids into dense and compact granules offers a new dimension for
      wastewater treatment. Compared with conventional biological flocs, aerobic
      granules are characterized by well-defined shape and compact buildup, superior
      biomass retention, enhanced microbial functions, and resilient to toxicity and
      shock loading. This review provides an up-to-date account on development in
      aerobic granulation and its applications. Granule characterization, factors
      affecting granulation, and response of granules to various environmental and
      operating conditions are discussed. Maintaining granule of adequate structural
      stability is one of the main challenges for practical applications of aerobic
      granulation. This paper also reviews recent advances in addressing granule
      stability and storage for use as inoculums, and as biomass supplement to enhance
      treatment efficiency. Challenges and future work of aerobic granulation are also
      outlined.

PMID- 22383047
TI  - Evaluation of left ventricular mechanical work and energetics of normal hearts in
      SERCA2a transgenic rats.
AB  - Cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) is responsible for
      most of the Ca(2+) removal during diastole and a larger Ca(2+) handling energy
      consumer in excitation-contraction (E-C) coupling. To understand the cardiac
      performance under long-term SERCA2a overexpression conditions, we established
      SERCA2a transgenic (TG) Wistar rats to analyze cardiac mechanical work and
      energetics in normal hearts during pacing at 300 beats/min. SERCA2a protein
      expression was increased in TGI and TGII rats (F2 and F3 of the same father and
      different mothers). Mean left ventricular (LV) end-systolic pressure (ESP) and
      systolic pressure-volume area (PVA; a total mechanical energy per beat) at
      midrange LV volume (mLVV) were significantly larger in TGI rats and were
      unchanged in TGII rats, compared to those in non-TG [wildtype (WT)] littermates.
      Mean myocardial oxygen consumption per minute for E-C coupling was significantly
      increased, and the mean slope of myocardial oxygen consumption per beat (VO(2))
      PVA (systolic PVA) linear relation was smaller, but the overall O(2) cost of LV
      contractility for Ca(2+) is unchanged in all TG rats. Mean Ca(2+) concentration
      exerting maximal ESP(mLVV) in TGII rats was significantly higher than that in WT
      rats. The Ca(2+) overloading protocol did not elicit mitochondrial swelling in
      TGII rats. Tolerance to higher Ca(2+) concentrations may support the possibility
      for enhanced SERCA2a activity in TGII rats. In conclusion, long-term SERCA2a
      overexpression enhanced or maintained LV mechanics, improved contractile
      efficiency under higher energy expenditure for Ca(2+) handling, and improved
      Ca(2+) tolerance, but it did not change the overall O(2) cost of LV contractility
      for Ca(2+) in normal hearts of TG rats.

PMID- 22383049
TI  - Recombinant expression and characterization of L-asparaginase II from a
      moderately thermotolerant bacterial isolate.
AB  - A moderately thermotolerant bacterium belonging to Enterobacteriaceae, which can
      grow at 44.5  degrees C, was isolated from cow dung; L-asparaginase II gene was
      isolated by PCR, cloned, and expressed in pET 20b with pelB leader sequence and
      6* Histidine tag at the C-terminal end. The active protein from the soluble
      sonicated fraction was purified through nickel affinity chromatography. After
      characterization, the purified protein showed optimum activities at a temperature
      of 37  degrees C and in a buffer system of pH 6 to 7. The enzyme exhibited
      thermostability at 50  degrees C with a 33% and 28% of activity retention after
      45 and 60 min. The kinetic parameters for the enzyme were calculated from
      Lineweaver-Burk plot, and K(m) and V(max) were 0.89 mM and 0.18 U/mg,
      respectively.

PMID- 22383050
TI  - Bioethanol production involving recombinant C. thermocellum hydrolytic
      hemicellulase and fermentative microbes.
AB  - The enhancement of the biomass productivity of Escherichia coli cells harbouring
      the truncated 903 bp gene designated as glycoside hydrolase family 43 (GH43) from
      Clostridium thermocellum showing hemicellulase activity along with its further
      use in simultaneous saccharification and fermentation (SSF) process is described.
      (Phosphoric acid) H(3)PO(4)-acetone treatment and ammonia fibre expansion (AFEX)
      were the pretreatment strategies employed on the leafy biomass of mango, poplar,
      neem and asoka among various substrates owing to their high hemicellulose
      content. GH43 showed optimal activity at a temperature of 50  degrees C, pH 5.4
      with stability over a pH range of 5.0-6.2. A 4-fold escalation in growth of the
      recombinant E. coli cells was observed when grown using repeated batch strategy
      in LB medium supplemented with glucose as co-substrate. Candida shehatae
      utilizing pentose sugars was employed for bioethanol production. AFEX
      pretreatment proved to be better over acid-acetone technique. The maximum ethanol
      concentration (1.44 g/L) was achieved for AFEX pretreated mango (1%, w/v)
      followed by poplar with an ethanol titre (1.32 g/L) in shake flask experiments. A
      1.5-fold increase in ethanol titre (2.11 g/L) was achieved with mango (1%, w/v)
      in a SSF process using a table top 2-L bioreactor with 1 L working volume.

PMID- 22383051
TI  - Enhancement of the activity and enantioselectivity of lipase by sol-gel
      encapsulation immobilization onto beta-cyclodextrin-based polymer.
AB  - Candida rugosa lipase was encapsulated within a chemically inert sol-gel support
      prepared by polycondensation with tetraethoxysilane and octyltriethoxysilane in
      the presence of beta-cyclodextrin-based polymer. The catalytic activity of the
      encapsulated lipases was evaluated both in the hydrolysis of p
      nitrophenylpalmitate and the enantioselective hydrolysis of racemic Naproxen
      methyl ester. It has been observed that the percent activity yield of the
      encapsulated lipase was 65 U/g, which is 7.5 times higher than that of the
      covalently immobilized lipase. The beta-cyclodextrin-based encapsulated lipases
      had higher conversion and enantioselectivity compared with covalently immobilized
      lipase. The study confirms an excellent enantioselectivity (E >300) for the
      encapsulated lipase with an enantiomeric excess value of 98% for S-naproxen.

PMID- 22383052
TI  - [Focal nodular hyperplasia in a 12-year-old boy: case report and considerations].
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) is a benign hepatic tumor of unknown
      origin. It is only observed rarely in children (approximately 1-2% of all
      pediatric liver tumors). CASE REPORT: A 12-year-old boy who suffered from
      infectious mononucleosis with liver involvement and hepatomegaly underwent a
      sonographic scan of the liver at an external hospital 3 months after the
      infection disappeared which revealed a tumor of the left hepatic lobule.
      Subsequent further examination (abdominal CT and MRT scans) confirmed the
      diagnosis of a highly vascularized mass about 10 cm in diameter, suspicious for
      FNH. Due to the high vascularization no biopsy was performed. A preoperative
      angiographic coiling and complete surgical resection was carried out because of
      the size and morphologic uncertainty. The diagnosis of FNH was confirmed by
      histological examination. The annual sonographic examination at follow-up has
      been uneventful for a 4-year period. CONCLUSIONS: Due to the rarity the diagnosis
      of FNH in children can be difficult leading to differential diagnostic problems.
      Due to the risk of bleeding in larger size tumors a biopsy is a point of
      controversy. Complete resection and histopathological examination of FNHs in
      childhood is a mandatory therapeutic option, which may be indicated in large
      tumors or, as in the present case tumors of uncertain biological behaviour.

PMID- 22383053
TI  - Identification of male-produced aggregation pheromone of the curculionid beetle
      Sternechus subsignatus.
AB  - Analyses of the headspace volatiles produced by males and females of Sternechus
      subsignatus Boheman (Coleoptera: Curculionidae) revealed seven male-specific
      compounds. The major component was (E)-2-(3,3-dimethylcyclohexylidene)-ethanol,
      and the minor components were 1-(2'-hydroxyethyl)-1-methyl-2
      isopropenylcyclobutane (grandisol), 7-methyl-3-methyleneoct-6-en-1-ol, (Z)-2-(3,3
      dimethylcyclohexylidene)-ethanol, (Z)- and (E)-2-(3,3-dimethylcyclohexylidene)
      acetaldehyde, and (E)-2-(3,3-dimethylcyclohexylidene) acetic acid. The latter
      compound is described for the first time as a natural product. Only four of the
      seven identified compounds showed electrophysiological activity. Enantioselective
      gas chromatography showed that the natural grandisol is the (1R,2S)-stereoisomer.
      The major component, (E)-2-(3,3-dimethylcyclohexylidene)-ethanol, attracted S.
      subsignatus in olfactometer bioassays. Studies are in progress to evaluate the
      biological activity of the major component and the EAD-active mixture under field
      conditions.

PMID- 22383054
TI  - Purification of the photosynthetic reaction center from Heliobacterium
      modesticaldum.
AB  - We have developed a purification protocol for photoactive reaction centers (HbRC)
      from Heliobacterium modesticaldum. HbRCs were purified from solubilized membranes
      in two sequential chromatographic steps, resulting in the isolation of a fraction
      containing a single polypeptide, which was identified as PshA by LC-MS/MS of
      tryptic peptides. All polypeptides reported earlier as unknown proteins (in
      Heinnickel et al., Biochemistry 45:6756-6764, 2006; Romberger et al., Photosynth
      Res 104:293-303, 2010) are now identified by mass spectrometry to be the membrane
      bound cytochrome c (553) and four different ABC-type transporters. The purified
      PshA homodimer binds the following pigments: 20 bacteriochlorophyll (BChl) g, two
      BChl g', two 8(1)-OH-Chl a (F), and one 4,4'-diaponeurosporene. It lacks the PshB
      polypeptide binding the F(A) and F(B) [4Fe-4S] clusters. It is active in charge
      separation and exhibits a trapping time of 23 ps, as judged by time-resolved
      fluorescence studies. The charge recombination rate of the P(800) (+)F(X)(-)
      state is 10-15 ms, as seen before. The purified HbRC core was able to reduce
      cyanobacterial flavodoxin in the light, exhibiting a K (M) of 10 MUM and a k
      (cat) of 9.5 s(-1) under near-saturating light. There are ~1.6 menaquinones per
      HbRC in the purified complex. Illumination of frozen HbRC in the presence of
      dithionite can cause creation of a radical at g = 2.0046, but this is not a
      semiquinone. Furthermore, we show that high-purity HbRCs are very stable in
      anoxic conditions and even remain active in the presence of oxygen under low
      light.

PMID- 22383055
TI  - Detection, prevalence and analysis of emerging porcine parvovirus infections.
AB  - A number of newly identified porcine parvoviruses had been described during the
      last decade, but the presence and prevalence of these viruses are unknown in
      Hungary and only partly known for Europe. The present study was conducted to
      detect and measure the prevalence of these viruses, namely porcine parvovirus
      (PPV) 2, PPV3, PPV4, porcine bocavirus (PBoV) 1, PBoV2, PBo-likeV and the 6V and
      7V parvoviruses. The prevalence of PPV1 and porcine circovirus type 2 (PCV2) was
      also investigated. Faecal samples, blood serum samples, organ tissues, foetuses
      and semen were collected from different swine herds in Hungary and tested by
      polymerase chain reaction methods specific for the different viruses. The results
      indicated that all of the examined parvoviruses were present in Hungary, hence in
      Europe. The prevalence was 18.1% for PCV2, 0.5 % for PPV1, 6.4% for PPV2, 9.7%
      for PPV3, 6.4% for PPV4, 1.5% for PBo-likeV, 4.8% for PBoV1 and PBoV2 and 1.8%
      for 6V and 7V. Based on the analysis of partial PPV4 and PBo-likeV sequences,
      these viruses showed a high degree of sequence conservation, whereas PPV3 and the
      majority of PPV2, PBoV1, PBoV2, 6V and 7V sequences showed higher variability.
      Possible sites of recombination were also identified between PBoV1 and PBoV2
      genomes.

PMID- 22383056
TI  - Diverse population of a new bipartite begomovirus infecting tomato crops in
      Uruguay.
AB  - Several isolates of a novel begomovirus were characterized from tomato samples
      collected in northern Uruguay exhibiting disease symptoms associated with Bemisia
      tabaci infestations. Analysis of full-length sequences of DNA-A and DNA-B
      components revealed the presence of a new begomovirus with the typical genome
      organization of a New World begomovirus, for which the name tomato rugose yellow
      leaf curl virus (ToRYLCV) is proposed. A high degree of nucleotide sequence
      diversity was found for both components, suggesting the presence of a diverse
      virus population. Recombination analysis suggested relationships of ToRYLCV to
      begomoviruses reported from the New World. Although common regions from DNA-As
      and DNA-Bs were surprisingly divergent for a cognate pair, a DNA-A and DNA-B pair
      cloned from one sample were infectious in Nicotiana benthamiana and tomato and
      reproduced symptoms observed in field-infected tomato plants, suggesting that
      ToRYLCV is the causal agent of the disease observed. This is the first report of
      a begomovirus infecting tomato crops in Uruguay and of the presence of
      begomovirus in this country.

PMID- 22383057
TI  - Complete nucleotide sequence of a severe isolate of cucumber vein yellowing virus
      from Jordan.
AB  - The complete genome of a severe isolate of Cucumber vein yellowing virus (CVYV)
      from Jordan was sequenced. Comparison with the genome of a Spanish CVYV isolate
      inducing very mild symptoms in cucumber cultivars revealed a nucleotide identity
      of 94% for the complete genome and an amino acid identity of 96% for the coding
      region. Comparison of synonymous and non-synonymous substitutions suggested a
      negative selection at amino acid and nucleotide levels with different degrees
      depending on the different coding regions. Finally, specific amino acid changes
      in the zinc finger domain of P1b and in the P1-P3 proteolytic site were found
      which could be involved in the virulence of CVYV.

PMID- 22383058
TI  - Case-control study of hepatitis B and hepatitis C in older adults: Do healthcare
      exposures contribute to burden of new infections?
AB  - Reports of hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission
      associated with unsafe medical practices have been increasing in the United
      States. However, the contribution of healthcare exposures to the burden of new
      infections is poorly understood outside of recognized outbreaks. We conducted a
      case-control study at three health departments that perform enhanced viral
      hepatitis surveillance in New York and Oregon. Reported cases of symptomatic
      acute hepatitis B and hepatitis C occurring in persons>=55 years of age from 2006
      to 2008 were enrolled. Controls were identified using telephone directories and
      matched to individual cases by age group (55-59, 60-69, and >=70 years) and
      residential postal code. Data collection covered exposures within 6 months before
      symptom onset (cases) or date of interview (controls). Forty-eight (37 hepatitis
      B and 11 hepatitis C) case and 159 control patients were enrolled. Case patients
      were more likely than controls to report one or more behavioral risk exposures,
      including sexual or household contact with an HBV or HCV patient, >1 sex partner,
      illicit drug use, or incarceration (21% of cases versus 4% of controls exposed;
      matched odds ratio [mOR]=7.1; 95% confidence interval [CI]: 2.1, 24.1). Case
      patients were more likely than controls to report hemodialysis (8% of cases;
      mOR=13.0; 95% CI: 1.5, 115), injections in a healthcare setting (58%; mOR=2.7;
      95% CI: 1.3, 5.3), and surgery (33%; mOR=2.3; 95% CI: 1.1, 4.7). In a
      multivariate model, behavioral risks (adjusted OR [aOR]=5.4; 95% CI: 1.5, 19.0;
      17% attributable risk), injections (aOR=2.7; 95% CI: 1.3, 5.8; 37% attributable
      risk), and hemodialysis (aOR=11.5; 95% CI: 1.2, 107; 8% attributable risk) were
      associated with case status. CONCLUSION: Healthcare exposures may represent an
      important source of new HBV and HCV infections among older adults.

PMID- 22383059
TI  - Antimicrobial constituents from the tubers of Bletilla ochracea.
AB  - A new 2-(2-methylpropyl)butanedioic acid derivative, bletillin A ( 1), and a new
      bibenzyl, bletillin B ( 2), together with seventeen known compounds ( 3- 19),
      were isolated from the tubers of Bletilla ochracea Schltr. Their structures were
      established by detailed spectroscopic analyses. Phenanthrenes ( 12- 14) exhibited
      antibacterial activities against gram-positive bacteria Staphylococcus aureus, S.
      epidermidis, and Bacillus subtilis, with MIC values of 12.5-25 ug/mL.

PMID- 22383060
TI  - Correlation between anorectocele with the anterior anal canal and anorectal
      junction anatomy using echodefecography.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the relationship
      between the pathogenesis of anorectocele and the anatomy of the anal canal and
      anorectal junction using echodefecography. METHODS: The study was conducted on a
      total of 100 women with obstructed defecation, mean age 46.6 years, who underwent
      echodefecography. Patients were classified based on rectocele status into group
      I, without rectocele (n = 32); group II, grade I rectocele (n = 11); group III,
      grade II (n = 27); and group IV, grade III (n = 30). We identified the layers of
      the anterior anorectal wall and measured anterior external sphincter length,
      posterior external sphincter and puborectalis length, gap between anterior
      external sphincter and anorectal junction, anorectal wall thickness in 3
      locations: (1) proximal to anterior external anal sphincter; (2) anterior
      anorectal junction; (3) 1.0 cm proximal to anorectal junction. RESULTS: The
      anterior part of the external anal sphincter was significantly longer in group I
      (18.91 +/- 0.38 mm) than in group III (16.94 +/- 0.45 mm) (p < 0.05), and the
      length in group I was similar to that in group II (18.56 +/- 0.44 mm) (p =
      0.6223). The gap was significantly shorter in group I (21.24 +/- 0.97 mm) than in
      group III (25.04 +/- 0.82 mm) and group IV (23.82 +/- 0.80 mm) (p < 0.05). The
      length of the anterior part of the external anal sphincter as a percentage of the
      length of the posterior external anal sphincter together with the puborectalis
      muscle was a mean of 57.39 +/- 2.13% in group I, 56.01 +/- 1.581% in group II,
      47.77 +/- 1.48% in group III, and 50.45 +/- 1.61% in group IV, with a
      significantly higher percentage in group I than in groups III (p = 0.0126) and IV
      (p = 0.0007). No significant differences were identified between any of the
      groups regarding anorectal wall thickness at any of the 3 selected locations (p >
      0.05). The muscularis propria layer of the rectal wall was not identified in 2
      patients in group I (6.25%), 3 patients in group II (11.11%), and 3 patients in
      group III (10.00%), and 6 in group IV (8.82%), with no significant differences
      among groups. CONCLUSIONS: The pathogenesis of anorectocele may be associated
      with a shorter anterior part of the external anal sphincter and consequently a
      longer gap.

PMID- 22383061
TI  - Integration of a maxillary model into facial surface stereophotogrammetry.
AB  - AIMS: Three-dimensional (3D) integration of a maxillary model into a facial model
      has only been possible by a complex procedure using face bow transfer after
      taking impressions of certain maxillary and facial parts. In this study, we aimed
      to develop a method for integrating a scanned maxillary model into a scan
      realized facial model. MATERIAL AND METHODS: A total of 19 patients with the
      medical indication for cone-beam computed tomography (CBCT) and orthodontic
      treatment were included in this study. Facial and maxillary scans were also
      taken. The construction of the integrated surface model required 10 steps. This
      integration procedure was evaluated by taking ten 3D dentofacial linear segment
      measurements in the integrated scan and the CBCT. These results were analyzed
      using descriptive statistics. RESULTS: All measurements demonstrated good intra
      individual reliability. We observed almost perfect congruence between integrated
      scan and CBCT in vertical distances, while the sagittal measurements revealed
      more, yet clinically acceptable, deviations possibly caused by different error
      sources in either of the two methods. CONCLUSION: This new method is suitable for
      generating 3D integrated surface-scan models which can be used for growth and
      therapy control studies in orthodontics and other disciplines in the dentofacial
      fields. Since this method does not require ionizing radiation, it is highly
      recommendable as an application for children and adolescent patients.

PMID- 22383063
TI  - Influence of material choice on the force delivery of bimaxillary tooth
      positioners on canine malpositions.
AB  - OBJECTIVE: Since their introduction in 1945, tooth positioners have been used to
      treat a range of malpositions. Although the original appliance was made of
      natural rubber, today's tooth positioners are fabricated from various elastic,
      transparent materials. It was the aim of this study to evaluate the forces and
      moments produced by current positioners on various upper canine malpositions.
      MATERIAL AND METHODS: Seven positioners of different materials were tested on 11
      upper canine malpositions: 0.25, 0.5, 1 mm supraposition; 0.25, 0.5, 1 mm
      infraposition; 5 degrees , 10 degrees , 20 degrees  mesiorotation; 5 degrees 
      mesioinclination, 5 degrees  buccal root torque. We measured forces and moments
      in vitro after bite closure by 0.5 mm, and opening by 1 mm using a three
      dimensional robotic device. All measurements were taken in a temperature
      controlled environment at 36  degrees C. RESULTS: The forces and moments measured
      at the canine varied greatly among the different positioners, with the
      thermoformed EVA positioner showing much greater forces and moments in almost all
      malpositions. At initial closure, we observed intrusive forces of 6-32 N for
      suprapositions, 0-11 N intrusive forces for infrapositions, 0-20 Nmm for
      mesiorotations, 6-12 Nmm for mesioinclinations, and - 23 Nmm to 5 Nmm for buccal
      root torque. All positioners were most effective on suprapositioned teeth. Very
      low or negligible correctional forces and moments in conjunction with all
      infrapositions and 5 degrees  with rotation were noted. Labial root torque led to
      unpredictable moments. CONCLUSION: Positioner material plays a major role in
      delivering forces to the teeth. However, tooth positioners did not induce
      corrective forces in all the malpositions tested. Clinically relevant
      correctional forces or moments in conjunction with all suprapositions, rotations
      of 10 degrees  and 20 degrees  as well as mesial tipping of the canine were
      observed.

PMID- 22383065
TI  - Silver-promoted Friedel-Crafts reaction: concise total synthesis of (-)-ardeemin,
      (-)-acetylardeemin and (-)-formylardeemin.
AB  - Total syntheses of multidrug resistant inhibitors (-)-acetylardeemin 2a, (-)
      ardeemin 2b, and (-)-formylardeemin 3 have been achieved within 10 steps starting
      from bromopyrroloinoline 13. The key step involves direct alkylation of 13 with
      prenyl tributylstannane 11 to yield 12 via a silver-promoted asymmetric Friedel
      Crafts reaction. Highly efficient installation of the isoprenyl group allowed
      excellent overall yield. Moreover, the substrate scope of the asymmetric Friedel
      Crafts reaction of 13 was expanded to include a variety of arenes 14 to afford
      natural product-like library analogues 15.

PMID- 22383064
TI  - In vitro cyclic shear fatigue of the bracket-adhesive complex: a pilot study.
AB  - OBJECTIVE: The aim of this study was to describe the effect of fatigue on the
      shear strength of the bracket-adhesive complex. MATERIALS AND METHODS: Brackets
      with laser-structured (Discovery(r), Dentaurum) and foil mesh bases (Ultra
      Minitrim(r), Dentaurum) were bonded onto silanized stainless steel flat plates
      with two chemically curing adhesives (No-Mix Bonding System, Dentaurum;
      ConciseTM, 3M Unitek) and aged in distilled water at 37 degrees C for 3 days. One
      group of specimens was used to determine shear-bond strength. The second group
      underwent shear-fatigue testing with a testing machine (Zwick 1445) according to
      the staircase method for 1,000 cycles, and the surviving specimens were subjected
      to shear-strength testing. The shear strength of the fatigued and non-fatigued
      specimens were then compared. RESULTS: Fatigued specimens demonstrated an 8% gain
      in shear strength in material group A (Discovery(r)/No-Mix) and a 10% loss of
      shear strength in material group D (Ultra-Minitrim(r)/ConciseTM) compared to the
      non-fatigued group. We observed no statistically significant differences in
      material groups B (Ultra-Minitrim(r)/No-Mix) and C (Discovery(r)/ConciseTM). The
      fatigue ratio varied between 60% and 67%. Among the non-fatigued specimens, the
      bracket Discovery(r) with laser-structured base showed circa 59% greater shear
      strength than the foil-mesh bracket Ultra-Minitrim(r), and the adhesive ConciseTM
      about 66% more shear strength than the No-Mix. CONCLUSION: Shear fatigue of the
      bracket-adhesive complex for 1,000 cycles revealed a variable, material-dependent
      influence on the shear strength of the bracket-adhesive complex. However, the
      effect of fatigue on shear strength was less significant than the effect of other
      factors such as bracket and adhesive type.

PMID- 22383066
TI  - Hypolipidemic effect of avocado (Persea americana Mill) seed in a
      hypercholesterolemic mouse model.
AB  - Avocado seed contains elevated levels of phenolic compounds and exhibits
      antioxidant properties. We investigated the effect of Avocado Seed Flour (ASF) on
      the lipid levels in mice on a hyperlipidemic diet. The concentration of phenols
      was determined by high-performance liquid chromatography, antioxidant activity
      was evaluated using the Trolox equivalent antioxidant capacity method, and
      dietary fiber was measured using the Association of Official Analytical Chemists
      (AOAC) method. The LD50 of ASF was determined using Lorke's method and
      hypolipidemic activity was evaluated in a hypercholesterolemic model in mice.
      Protocatechuic acid was the main phenolic compound found in ASF, followed by
      kaempferide and vanillic acid. The total phenolic content in the methanolic
      extract of ASF was 292.00 +/- 9.81 mg gallic acid equivalents/g seed dry weight
      and the antioxidant activity resulted in 173.3 MUmol Trolox equivalents/g DW. In
      addition, a high content of dietary fiber was found (34.8%). The oral LD50 for
      ASF was 1767 mg/kg body weight, and treatment with ASF significantly reduced the
      levels of total cholesterol, LDL-C, and prediction of the atherogenic index.
      Therefore, the antioxidant activity of phenolic compounds and dietary fiber in
      ASF may be responsible for the hypocholesterolemic activity of ASF in a
      hyperlipidemic model of mice.

PMID- 22383067
TI  - Spherical ordered mesoporous carbon nanoparticles with high porosity for lithium
      sulfur batteries.

PMID- 22383068
TI  - Profiling phlorotannins in brown macroalgae by liquid chromatography-high
      resolution mass spectrometry.
AB  - INTRODUCTION: Phlorotannins, phenolic compounds produced exclusively by
      Phaeophyceae (brown algae), have recently been associated with a wide variety of
      beneficial bioactivities. Several studies have measured the total phenolic
      content in extracts from various species, but little characterisation of
      individual phlorotannin components has been demonstrated. OBJECTIVE: The purpose
      of this study was to develop a liquid chromatography-mass spectrometry (LC-MS)
      based method for rapid profiling of phlorotannins in brown algae. METHODOLOGY:
      Phlorotannin-enriched extracts from five phaeophyceaen species were analysed by
      ultrahigh-pressure liquid chromatography (UHPLC) operating in hydrophilic
      interaction liquid chromatography (HILIC) mode combined with high resolution mass
      spectrometry (HRMS). The method was optimised using an extract of Fucus
      vesiculosus; separation was achieved in less than 15 min. The basic mobile phase
      enhanced negative-ion electrospray ionisation (ESI), and generated multiply
      charged ions that allowed detection of high molecular weight phlorotannins.
      RESULTS: The phlorotannin profiles of Pelvetia canaliculata, Fucus spiralis, F.
      vesiculosus, Ascophyllum nodosum and Saccharina longicruris differed
      significantly. Fucus vesiculosus yielded a high abundance of low molecular weight
      (< 1200 Da) phlorotannins, while P. canaliculata exhibited a more evenly
      distributed profile, with moderate degrees of polymerisation ranging from 3 to
      49. HRMS enabled the identification of phlorotannins with masses up to 6000 Da
      using a combination of accurate mass and 13C isotopic patterns. CONCLUSION: The
      UHPLC-HRMS method described was successful in rapidly profiling phlorotannins in
      brown seaweeds based on their degree of polymerisation. HILIC was demonstrated to
      be an effective separation mode, particularly for low molecular weight
      phlorotannins.

PMID- 22383069
TI  - CT and MRI findings in the basal ganglia in non-ketotic hyperglycaemia associated
      hemichorea and hemi-ballismus (HC-HB).

PMID- 22383070
TI  - Correlation between the cord vitamin D levels and regulatory T cells in newborn
      infants.
AB  - Vitamin D is important for calcium homeostasis, muscle, and bone health. It has
      also immunomodulatory capacities in vivo and in vitro. Regulatory T cells (Treg)
      have been found to suppress a number of T cell-mediated immune disorders,
      including allergic responses and autoimmune diseases. This study aimed to
      investigate the correlation between 25-hydroxyvitamin D (25(OH)D) levels and the
      regulatory T cells in cord blood. The study group is comprised of 101 full-term
      newborn infants. Umbilical cord 25(OH)D levels and number and percentage of T
      lymphocyte, T helper, and Treg cells were measured. Infants were grouped
      according to 25-hydroxyvitamin D levels (25(OH)D <12 ng/ml and 25(OH)D >12 ng/ml)
      (converting factor of 25OHD level into SI unit, 2.6). Severe vitamin D deficiency
      (25(OH)D <12 ng/ml) was observed in 32% of the infants. There was no significant
      correlation between 25-hydroxyvitamin D levels and T cell number and percentages.
      There were also no significant differences in white blood cell, total lymphocyte
      count, T helper, and Treg cell percentage and number between groups. These
      results suggest that the serum level of 25-hydroxyvitamin D is not crucially
      involved in the correlation between vitamin D status and T cell regulation in
      cord blood.

PMID- 22383071
TI  - Congenital and infantile cataract: aetiology and management.
AB  - Congenital cataract is the commonest worldwide cause of lifelong visual loss in
      children. Although congenital cataracts have a diverse aetiology, in many
      children, a cause is not identified; however, autosomal dominant inheritance is
      commonly seen. Early diagnosis either on the post-natal ward or in the community
      is important because appropriate intervention can result in good levels of visual
      function. However, visual outcome is largely dependent on the timing of surgery
      when dense cataracts are present. Good outcomes have been reported in children
      undergoing surgery before 6 weeks of age in children with unilateral cataract and
      before 10 weeks of age in bilateral cases. Placement of an artificial intraocular
      lens implant after removal of the cataract has become established practice in
      children over 2 years of age. There remains debate over the safety and
      predictability of intraocular lens implantation in infants. Despite early surgery
      and aggressive optical rehabilitation, children may still develop deprivation
      amblyopia, nystagmus, strabismus, and glaucoma. The diagnosis and management of
      congenital cataracts has improved substantially over the past 30 years with a
      concurrent improvement in outcomes for affected children. Many aspects of the pre
      , intra-, and postoperative management of these patients continue to be refined,
      highlighting the need for good quality data and prospective collaborative studies
      in this field.

PMID- 22383072
TI  - Birth weight and overweight/obesity in adults: a meta-analysis.
AB  - The objective of this study is to assess the association between birth weight and
      overweight/obesity in adults. The following MeSH terms were used: "birth weight,"
      "obesity," "overweight." Fifteen studies involving a total of 211,457 persons
      were identified. Low birth weight (<2,500 g), as compared with normal birth
      weight (2,500-4,000 g), was not associated with increased risk of
      overweight/obesity (OR = 1.17, 95% CI 0.94, 1.46). High birth weight (>= 4,000
      g), as compared with normal birth weight, was associated with increased risk of
      overweight/obesity (OR = 1.46, 95% CI 1.27, 1.68). Low birth weight compared with
      normal birth weight, the total mean difference of BMI decreased 0.14 kg/m(2).
      High birth weight compared with normal birth weight, the total mean difference of
      BMI increased 0.76 kg/m(2). Low birth weight, as compared with a birth weight of
      >= 2,500 g, was not significantly associated with decreased risk of obesity (OR =
      1.12, 95% CI 0.90-1.40). High birth weight, as compared with a birth weight of
      <4,000 g, was associated with increased risk of obesity (OR = 1.43, 95% CI 1.25
      1.64). Low birth weight compared with birth weight >= 2,500 g, the total mean
      difference of BMI was decreased 0.42 kg/m(2); high birth weight compared with
      birth weight <4,000 g, the total mean difference of BMI was increased 0.79
      kg/m(2). CONCLUSION: Neither positively linear nor J- or U-shaped relations exist
      between birth weight and overweight/obesity in adults. It is high birth weight,
      not low birth weight, that is associated with increased risk of
      overweight/obesity in adults.

PMID- 22383073
TI  - Diagnosing Hunter syndrome in pediatric practice: practical considerations and
      common pitfalls.
AB  - Mucopolysaccharidosis II (MPS II), or Hunter syndrome, is an X-linked lysosomal
      storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase.
      Affected patients suffer progressive damage to multiple organ systems and early
      mortality. Two thirds of patients also manifest cognitive impairment and
      developmental delays. MPS II can be extremely difficult to diagnose before
      irreversible organ and tissue damage has occurred because of an insidious onset
      and the overlap in signs and symptoms with common childhood complaints. This is
      particularly true of patients without cognitive impairment (attenuated
      phenotype). Although not curative, early treatment with enzyme replacement
      therapy before irreversible organ damage has occurred may result in the greatest
      clinical benefit. Here, the signs, symptoms, and surgical history that should
      trigger suspicion of MPS II are described, and the diagnostic process is reviewed
      with a focus on practical considerations and the avoidance of common diagnostic
      pitfalls. Once a diagnosis is made, multidisciplinary management with an extended
      team of pediatric specialists is essential and should involve the pediatrician or
      family practice physician as facilitator and medical home for the patient and
      family. CONCLUSION: Because routine newborn screening is not yet available for
      MPS II, the involvement and awareness of pediatricians, family practice
      physicians, and pediatric specialists is critical for early identification,
      diagnosis, and referral in order to help optimize patient outcomes.

PMID- 22383074
TI  - Microbiological aspects of vulvovaginitis in prepubertal girls.
AB  - This study aimed to establish the vaginal introitus microbial flora in girls with
      and without symptoms of vulvovaginitis, and to present the distribution of
      isolated microorganisms by age groups in girls with vulvovaginitis. We enrolled
      500 girls with vulvovaginitis symptoms, aged 2-12 years, referred by their
      pediatricians for microbiological examination of the vaginal introitus swabs, and
      30 age-matched asymptomatic girls. Similar microbial flora was isolated in both
      groups, but the symptomatic girls had significantly more common positive
      microbiological findings compared to controls (p < 0.001). In symptomatic girls,
      the following pathogenic bacteria were isolated: Streptococcus pyogenes (4.2%),
      Haemophilus influenzae (0.4%), and Staphylococcus aureus (5.8%). Bacteria of
      fecal origin were found in vaginal introitus swabs in 33.8% of cases, most
      commonly Proteus mirabilis (14.4%), Enterococcus faecalis (12.2%), and
      Escherichia coli (7.0%). The finding of fecal flora was more common compared to
      controls, reaching a statistical significance (p < 0.05), as well as in girls
      aged up to 6 years (p < 0.001). Candida species were found in 2.4% of girls with
      vulvovaginitis symptoms. CONCLUSION: The microbial ecosystem in girls with
      clinical signs of vulvovaginitis is complex and variable, and the presence of a
      microorganism does not necessarily imply that it is the cause of infection. The
      diagnosis of vulvovaginitis in prepubertal girls requires a complex and
      comprehensive approach, and microbiological findings should be interpreted in the
      context of clinical findings.

PMID- 22383075
TI  - Basic science and surgical treatment options for articular cartilage injuries of
      the knee.
AB  - The complex structure of articular cartilage allows for diverse knee function
      throughout range of motion and weight bearing. However, disruption to the
      structural integrity of the articular surface can cause significant morbidity.
      Due to an inherently poor regenerative capacity, articular cartilage defects
      present a treatment challenge for physicians and therapists. For many patients, a
      trial of nonsurgical treatment options is paramount prior to surgical
      intervention. In instances of failed conservative treatment, patients can undergo
      an array of palliative, restorative, or reparative surgical procedures to treat
      these lesions. Palliative methods include debridement and lavage, while
      restorative techniques include marrow stimulation. For larger lesions involving
      subchondral bone, reparative procedures such as osteochondral grafting or
      autologous chondrocyte implantation are considered. Clinical success not only
      depends on the surgical techniques but also requires strict adherence to
      rehabilitation guidelines. The purpose of this article is to review the basic
      science of articular cartilage and to provide an overview of the procedures
      currently performed at our institution for patients presenting with symptomatic
      cartilage lesions.

PMID- 22383077
TI  - Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in
      male albino rats through the alleviation of oxidative stress.
AB  - The present work was focused to evaluate the ameliorative property of aqueous
      extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic
      induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered
      orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to
      oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were
      sacrificed for the evaluation of body weights, organ weights, hematological
      profile, serum biochemical profile, and hepatic and renal antioxidative
      parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione
      S-transferase, glutathione peroxidase, glutathione reductase, superoxide
      dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit
      at both doses markedly and significantly normalized body weights, organ weights,
      hematological profiles, and serum biochemical profile in arsenic-treated animals.
      Further, AQ T. dioica fruit pretreatment significantly modulated all the
      aforesaid hepatic and renal biochemical perturbations and reduced DNA
      fragmentation in arsenic-intoxicated rats. Therefore, from the present findings,
      it can be concluded that T. dioica fruit possessed remarkable value in
      amelioration of arsenic-induced hepatic and renal toxicity, mediated by
      alleviation of arsenic-induced oxidative stress by multiple mechanisms in male
      albino rats.

PMID- 22383078
TI  - Efficacy of dietary chromium (III) supplementation on tissue chromium deposition
      in finishing pigs.
AB  - The study was conducted to evaluate the efficacy of different forms of trivalent
      chromium (Cr) supplementation on tissue chromium deposition in finishing pigs. A
      total of 96 pigs with an initial average body mass 65.57+/-1.05 kg were blocked
      by body mass and randomly assigned to four treatments with three replicates. Pigs
      were offered one of four diets including a control diet or the control diet
      supplemented with 200 MUg/kg chromium from either chromium chloride (CrCl(3)),
      chromium picolinate (CrPic) or chromium nanocomposite (CrNano) for 40 days.
      During the trial, all pigs were given free access to feed and water. After
      feeding trial, eight pigs from each treatment were slaughtered for samples
      collection. The results showed that supplemental CrNano increased Cr content in
      blood, longissimus muscle, heart, liver, kidney, jejunum, and ileum (P<0.05).
      Supplemental Cr from three sources increased Cr excretion from all feces
      (P<0.05). Urinary Cr excretion was increased by CrNano or CrPic supplementation
      significantly. These results suggested that chromium nanocomposite exhibited more
      effective on tissue Cr deposition in pigs, which indicated higher absorption
      compared with CrCl(3) and CrPic.

PMID- 22383079
TI  - Alterations of serum zinc, copper, manganese, iron, calcium, and magnesium
      concentrations and the complexity of interelement relations in patients with
      obsessive-compulsive disorder.
AB  - The purpose of the present study was to evaluate the status of serum trace
      elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in
      obsessive-compulsive disorder patients. Forty-eight obsessive-compulsive disorder
      patients and 48 healthy volunteers were included in this study. Patients were
      recruited from Bangabandhu Sheikh Mujib Medical University by random sampling.
      Serum trace element concentrations were determined using flame atomic absorption
      spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite
      furnace atomic absorption spectroscopy (for manganese). Data were analyzed using
      independent t test, Pearson's correlation analysis, regression analysis, and
      ANOVA. Statistical analysis of these data showed a definite pattern of variation
      among certain elements in patients with obsessive-compulsive disorder compared to
      controls. In patients' serum, zinc, iron, and magnesium concentrations decreased
      significantly (p<0.05) compared to the controls. Serum manganese and calcium
      concentrations were significantly higher (p<0.05) in patients compared to the
      controls. These data showed a definite imbalance in the interelement relations in
      obsessive-compulsive disorder patients compared to controls and therefore suggest
      a disturbance in the element homeostasis.

PMID- 22383080
TI  - Neutrophil infiltration of the colon is independent of the FPR1 yet FPR1
      deficient mice show differential susceptibilities to acute versus chronic induced
      colitis.
AB  - BACKGROUND: The receptor for formylated peptides, formyl peptide receptor 1
      (FPR1), potently activates and serves as a chemoattractant receptor for
      neutrophils. AIM: Given the abundance of neutrophils in the inflamed colon, our
      aim was to determine if the FPR1 mediates colonic neutrophil migration, using the
      dextran sodium sulfate (DDS)-induced model of colitis. METHODS: Formyl peptide
      receptor 1 gene-deficient mice were administered DDS in drinking water for a
      single 5-day period (acute) or in two 5-day periods separated by 16 days
      (chronic). At the end of the treatment their colons were excised, measured, and
      prepared for histological evaluation. RESULTS: FPR1(-/-) mice experienced less
      severe acute colonic pathology than C57BL/6 (wildtype) mice. The opposite was
      observed following the second colitis cycle, with FPR1(-/-) mice developing worse
      pathology than wildtype mice. Both strains had similar numbers of infiltrating
      neutrophils in ulcerated areas of the colon after a single DSS cycle, but FPR1(-/
      ) mice had significantly more neutrophils in the ulcerated mucosa after two
      cycles. There was no difference in the capacity of neutrophils from each strain
      to migrate to chemoattractants. Since the FPR1(-/-) mice had larger ulcers
      compared to the wildtype mice, we propose that the FPR1(-/-) mice failed to
      recover at the same rate as wildtype mice. This apparent difference in
      restitution could not be attributed to observable differences in annexin A1.
      CONCLUSIONS: We conclude that neutrophil migration into the inflamed mouse colon
      does not depend on FPR1 but that FPR1 contributes in other pathological
      mechanisms that are harmful during acute inflammation but protective during
      chronic inflammation.

PMID- 22383081
TI  - beta-Cell dysfunction in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by
      irreversible destruction of pancreatic secretory parenchyma, fibrosis, exocrine
      atrophy, and endocrine insufficiency leading to diabetes. Secondary diabetes
      occurring in CP subsequent to destruction of pancreatic beta-cells is distinct,
      since it involves beta-cell dysfunction amidst an inflammatory milieu. Even
      though considerable knowledge is available on the pathophysiology and clinical
      management of CP, relatively much less is known about the molecular events
      leading to beta-cell dysfunction. Investigators have demonstrated that altered
      morphology, reduced beta-cell mass, and beta-cell numbers result in endocrine
      insufficiency. However, recent reports and our observations suggest that beta
      cell dysfunction develops in the early stages of CP while clinical diabetes
      manifests later, when there is profound fibrosis. In the early stages, altered
      internal milieu and physiology arising due to inflammation and release of
      cytokines might lead to deranged signaling pathways and islet dysfunction.
      Subsequently, development of fibrosis causes islet destruction. This suggests
      that endocrine deficiency in CP is multifactorial. Although the role of
      transcription factors (Pdx-1, MafA, NeuroD) on beta-cell functions is understood,
      alterations in internal milieu of pancreatic tissue that affects beta-cell
      functions in CP has not been elucidated. In this review, we summarize the factors
      that have an effect on islet functions. Understanding molecular events of beta
      cell dysfunction in CP can lead to the development of targeted preventive and
      therapeutic modalities.

PMID- 22383082
TI  - Clinical characteristics of young-onset ischemic colitis.
AB  - BACKGROUND: Ischemic colitis (IC) typically develops in the elderly, where
      hypertension, cerebrocardiovascular disease, and past history of abdominal
      surgery are regarded as risk factors. Although there have been reports of younger
      patients with IC, its clinical features remain unclear. AIM: The aim of this
      study was to clarify the clinical characteristics of IC in young adults. METHODS:
      Three hundred fifty-nine patients were diagnosed as having IC at five hospitals
      across Nagano prefecture, Japan. Clinical data were compared between the young
      patient group [20-45 years, n = 53 (15%)] and the elderly patient group [>45
      years, n = 306 (85%)], as well as with age- and gender-matched healthy
      individuals (n = 156). RESULTS: The presence of a smoking habit and hyperuricemia
      were significantly higher in the young patient group compared with the elderly
      patient group (42 vs. 19%, P = 0.001 and 8 vs. 1%, P = 0.019, respectively),
      which was confirmed by multiple logistic regression analysis (P = 0.001, odds
      ratio 3.239 and P = 0.028, odds ratio 16.907, respectively). Additionally,
      multiple logistic regression analysis of the young IC patient group and age- and
      gender-matched healthy individuals demonstrated that these two factors were
      strongly associated with IC development (P = 0.008, odds ratio 2.49 for smoking
      habit and P = 0.039, odds ratio 6.37 for hyperuricemia). CONCLUSIONS: High
      prevalences of a smoking habit and hyperuricemia are characteristic features of
      IC in the young adult population.

PMID- 22383083
TI  - The effect of CO2 availability on the growth, iron oxidation and CO2-fixation
      rates of pure cultures of Leptospirillum ferriphilum and Acidithiobacillus
      ferrooxidans.
AB  - Understanding how bioleaching systems respond to the availability of CO(2) is
      essential to developing operating conditions that select for optimum microbial
      performance. Therefore, the effect of inlet gas and associated dissolved CO(2)
      concentration on the growth, iron oxidation and CO(2) -fixation rates of pure
      cultures of Acidithiobacillus ferrooxidans and Leptospirillum ferriphilum was
      investigated in a batch stirred tank system. The minimum inlet CO(2)
      concentrations required to promote the growth of At. ferrooxidans and L.
      ferriphilum were 25 and 70 ppm, respectively, and corresponded to dissolved CO(2)
      concentrations of 0.71 and 1.57 uM (at 30 degrees C and 37 degrees C,
      respectively). An actively growing culture of L. ferriphilum was able to maintain
      growth at inlet CO(2) concentrations less than 30 ppm (0.31-0.45 uM in solution).
      The highest total new cell production and maximum specific growth rates from the
      stationary phase inocula were observed with CO(2) inlet concentrations less than
      that of air. In contrast, the amount of CO(2) fixed per new cell produced
      increased with increasing inlet CO(2) concentrations above 100 ppm. Where inlet
      gas CO(2) concentrations were increased above that of air the additional CO(2)
      was consumed by the organisms but did not lead to increased cell production or
      significantly increase performance in terms of iron oxidation. It is proposed
      that At. ferrooxidans has two CO(2) uptake mechanisms, a high affinity system
      operating at low available CO(2) concentrations, which is subject to substrate
      inhibition and a low affinity system operating at higher available CO(2)
      concentrations. L. ferriphilum has a single uptake system characterised by a
      moderate CO(2) affinity. At. ferrooxidans performed better than L. ferriphilum at
      lower CO(2) availabilities, and was less affected by CO(2) starvation. Finally,
      the results demonstrate the limitations of using CO(2) uptake or ferrous iron
      oxidation data as indirect measures of cell growth and performance across varying
      physiological conditions.

PMID- 22383084
TI  - A case of intrapulmonary transmission of air while transitioning a patient from a
      sitting to a supine position after venous air embolism during a craniotomy.
AB  - PURPOSE: Since certain surgical procedures still require a sitting or reverse
      Trendelenburg position, it remains important to evaluate the risk for paradoxical
      embolization. Intracardiac shunting, the most common cause being a patent foramen
      ovale, can be excluded by contrast-enhanced transesophageal echocardiography.
      There are, however, less described cases which result from patency of
      intrapulmonary functional arteriovenous anastomoses and lead to extra-cardiac
      paradoxical air embolism during anesthesia. We report a unique case to increase
      awareness of this real and potentially dangerous complication. CLINICAL FEATURES:
      A 52-yr-old male was scheduled for resection of a tumour at the cerebellopontine
      angle. Preoperative evaluation excluded intracardiac shunts. During a craniotomy
      in the sitting position, recurrent venous air emboli entered the patient's right
      heart, leading to a sudden decline in end-tidal CO(2), an increase in PaCO(2),
      and a reduction of PaO(2). The exact source of surgical entrance could not be
      identified; therefore, the surgical wound was closed provisionally and the
      patient was repositioned supine to prevent further venous air emboli. During
      transition to the supine position, we observed clinically significant crossover
      of air into the left heart originating from the left pulmonary vein, as detected
      by transesophageal echocardiography. In all likelihood, the etiology was an
      opening of intrapulmonary right-to-left anastomoses. The patient recovered
      without neurological or pulmonary sequelae. CONCLUSION: In the presence of
      massive venous air emboli, intrapulmonary right-to-left paradoxical air emboli
      can occur while intraoperatively transitioning a patient from the sitting to the
      supine position.

PMID- 22383085
TI  - Esmolol versus ketamine-remifentanil combination for early postoperative
      analgesia after laparoscopic cholecystectomy: a randomized controlled trial.
AB  - PURPOSE: Controversy surrounds the optimal technique to moderate pain after
      laparoscopic cholecystectomy (LC). Opioid analgesics, sympatholytic drugs, and
      adjuvants, such as ketamine, have all been used. We compared esmolol with a
      combination of remifentanil plus ketamine in patients undergoing LC to determine
      the impact of these drugs on morphine requirements and pain control. METHODS:
      Sixty American Society of Anesthesiologists physical status I-II patients
      undergoing LC and anesthetized with sevoflurane were randomized to one of two
      groups. Group E patients received a bolus of esmolol 0.5 mg.kg(-1) iv at
      induction followed by an infusion of 5-15 MUg.kg(-1).min(-1), and Group R-K
      patients received a bolus of ketamine 0.5 mg.kg(-1) iv and remifentanil 0.5
      MUg.kg(-1) iv at induction followed by a remifentanil infusion titrated over a
      range of 0.1-0.5 MUg.kg(-1).min(-1). All patients received paracetamol,
      dexketoprofen, and levobupivacaine via infiltration of laparoscopic port sites.
      After surgery, a predetermined bolus of morphine was administered according to a
      verbal numerical rating scale (VNRS) for pain intensity. The primary outcome of
      interest was postoperative morphine requirement. RESULTS: Median consumption of
      morphine was higher in Group R-K than in Group E (5 mg [4-6] vs 0 mg [0-2],
      respectively; P < 0.001). In the postanesthesia care unit, patients in Group R-K
      had higher pain scores than patients in Group E (difference in maximum VNRS, -11;
      95% confidence interval (CI), -19 to -3). The concentration of sevoflurane to
      maintain a bispectral index~40 was higher in Group E than in Group R-K (between
      group difference 0.3%; 95% CI, 0.15 to 0.40). The incidence of postoperative
      nausea and vomiting was similar between the two groups. CONCLUSION:
      Intraoperative esmolol infusion reduces morphine requirements and provides more
      effective analgesia compared with a combination of remifentanil-ketamine given by
      infusion in patients undergoing LC.

PMID- 22383086
TI  - Intrathecally administered ropivacaine is less neurotoxic than procaine,
      bupivacaine, and levobupivacaine in a rat spinal model.
AB  - PURPOSE: The aim of this study was to compare the neurotoxicity of intrathecal
      procaine, bupivacaine, levobupivacaine, and ropivacaine in an animal model.
      METHODS: The study comprised two experiments. In the concentration experiment,
      rats (n = 78) were administered 0.12 MUL.g(-1) body weight (BW) of 2% or 20%
      procaine, 0.5% or 5% bupivacaine, 0.5% or 5% levobupivacaine, or 0.5% or 5%
      ropivacaine. Based on the findings, the doses were increased by volume in the
      subsequent volume experiment using 0.12, 0.24, or 0.48 MUL.g(-1) BW of 6%
      procaine, 6% levobupivacaine, or 6% ropivacaine (n = 79). Walking behaviour and
      sensory threshold were analyzed, and a histological examination of the spinal
      cord, posterior and anterior roots, and cauda equina was performed. RESULTS: The
      concentration experiment showed abnormalities only in the 5% bupivacaine group,
      and these abnormal findings were in the posterior root (PR) and posterior column
      (PC). The volume experiment revealed that procaine 0.24 MUL.g(-1) was neurotoxic,
      mainly affecting the PR. At 0.48 MUL.g(-1), severe injury was observed in the PR
      and PC in all six procaine rats and four of six levobupivacaine rats, while
      milder injury was limited to the PR in one of six ropivacaine rats, which
      differed significantly from the former two groups (P = 0.006 and P = 0.014,
      respectively). Electron microscopy showed axonal degeneration. CONCLUSION: All
      four local anesthetics seemed to cause identical neurotoxic lesions commencing in
      the PR and extending to the PC by axonal degeneration. Bupivacaine appeared to be
      the most neurotoxic of the four drugs, and the neurotoxicity at higher doses
      increased by volume with procaine > levobupivacaine > ropivacaine.

PMID- 22383087
TI  - Neuromuscular blockade for early severe acute respiratory distress syndrome: does
      sedation make the difference?

PMID- 22383088
TI  - Taurine suppresses osteoblastic differentiation of aortic valve interstitial
      cells induced by beta-glycerophosphate disodium, dexamethasone and ascorbic acid
      via the ERK pathway.
AB  - Aortic valve calcification (AVC) is an active process characterized by
      osteoblastic differentiation of the aortic valve interstitial cells (AVICs).
      Taurine is a free beta-amino acid and plays important physiological roles
      including protective effect of cardiovascular events. To evaluate the possible
      role of taurine in AVC, we isolated human AVICs from patients with type A
      dissection without leaflet disease. We demonstrated that the cultured AVICs
      express SM alpha-actin, vimentin and taurine transporter (TAUT), but not CD31, SM
      myosin or desmin. We also established the osteoblastic differentiation model of
      the AVICs induced by pro-calcific medium (PCM) containing beta-glycerophosphate
      disodium, dexamethasone and ascorbic acid in vitro. The results showed that
      taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by
      decreasing the alkaline phosphate (ALP) activity/expression and the expression of
      the core binding factor alpha1 (Cbfalpha1) in a dose-dependent manner (reaching
      the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the
      mineralization level of AVICs in the form of calcium content significantly.
      Furthermore, taurine activated the extracellular signal-regulated protein kinase
      (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect
      of taurine on both ALP activity/expression and Cbfalpha1 expression. These
      results suggested that taurine could inhibit osteoblastic differentiation of AVIC
      via the ERK pathway.

PMID- 22383089
TI  - Taurine protects cerebellar neurons of the external granular layer against
      ethanol-induced apoptosis in 7-day-old mice.
AB  - Acute alcohol administration is harmful especially for the developing nervous
      system, where it induces massive apoptotic neurodegeneration leading to alcohol
      related disorders of newborn infants. Neuroprotection against ethanol-induced
      apoptosis may save neurons and reduce the consequences of maternal alcohol
      consumption. Previously we have shown that taurine protects immature cerebellar
      neurons in the internal granular layer of cerebellum from ethanol-induced
      apoptosis. Now we describe a similar protective action for taurine in the
      external layer of cerebellum of 7-day-old mice. The mice were divided into three
      groups: ethanol-treated, ethanol + taurine-treated and controls. Ethanol (20%
      solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at
      time 0 h and 2.5 g/kg at 2 h) to the ethanol and ethanol + taurine groups. The
      ethanol + taurine group also received subcutaneously two injections of taurine (1
      g/kg each, 1 h before the first dose of ethanol and 1 h after the second dose of
      ethanol). To verify apoptosis, immunostaining for activated caspase-3 and TUNEL
      staining were made in the mid-sagittal sections containing lobules I-X of the
      cerebellar vermis at 8 h after the first ethanol injection. Ethanol induced
      apoptosis in the cerebellar external granular layer. Taurine treatment
      significantly reduced the number of activated caspase-3-immunoreactive and TUNEL
      positive cells. Taurine has thus a neuroprotective antiapoptotic action in the
      external granular layer of the cerebellum, preserving a number of neurons from
      ethanol-induced apoptosis.

PMID- 22383090
TI  - Lipid metabolism in pigs fed supplemental conjugated linoleic acid and/or dietary
      arginine.
AB  - We proposed that the combination of conjugated linoleic acid (CLA) and arginine
      would decrease adiposity by depressing lipid synthesis in liver and adipose
      tissues of growing pigs. Pigs were allotted to treatments in a 2 * 2 factorial
      design with two lipids (CLA or canola oil) and two amino acids [L-arginine or L
      alanine (isonitrogenous control)]; supplements were provided from 80 to 110 kg
      body weight (approximately 4 weeks). Treatment groups (n = 4) were: control
      (2.05% L-alanine plus 1% canola oil); CLA (2.05% L-alanine plus 1% CLA); arginine
      (1.0% L-arginine plus 1.0% canola oil); arginine plus CLA (1.0% arginine plus
      1.0% CLA). Arginine increased backfat thickness (P = 0.07) in the absence or
      presence of CLA, and arginine supplementation increased subcutaneous and
      retroperitoneal adipocyte volume, especially in combination with dietary CLA
      (interaction P = 0.001). Arginine increased palmitate incorporation into total
      lipids by over 60% in liver (P = 0.07). Dietary CLA increased palmitate
      incorporation into lipids in longissimus muscle by over 100% (P = 0.01), and CLA
      increased longissimus muscle lipid by nearly 20%. CLA increased glucose oxidation
      to CO(2) by over 80% in retroperitoneal and subcutaneous adipose tissues (P =
      0.04), and doubled palmitate oxidation to CO(2) in intestinal duodenal mucosal
      cells (P = 0.07). Arginine supplementation decreased muscle pH at 45 min
      postmortem (P = 0.001), indicating elevated early postmortem glycolysis, and CLA
      and arginine independently increased PGC-1alpha gene expression in longissimus
      muscle. CLA but not arginine depressed mTOR gene expression in intestinal
      duodenal mucosal cells. CLA decreased serum insulin by 50% (P = 0.02) but
      increased serum triacylglycerols by over 40%. CLA supplementation increased (P <=
      0.01) total saturated fatty acids in liver and adipose tissue. In conclusion,
      neither CLA nor arginine depressed tissue lipid synthesis in growing/finishing
      pigs, and in fact dietary CLA promoted elevated intramuscular lipid and arginine
      increased carcass adiposity.

PMID- 22383092
TI  - Mechanoradicals created in "polymeric sponges" drive reactions in aqueous media.

PMID- 22383091
TI  - Head bobber: an insertional mutation causes inner ear defects, hyperactive
      circling, and deafness.
AB  - The head bobber transgenic mouse line, produced by pronuclear integration,
      exhibits repetitive head tilting, circling behavior, and severe hearing loss.
      Transmitted as an autosomal recessive trait, the homozygote has vestibular and
      cochlea inner ear defects. The space between the semicircular canals is enclosed
      within the otic capsule creating a vacuous chamber with remnants of the
      semicircular canals, associated cristae, and vestibular organs. A poorly
      developed stria vascularis and endolymphatic duct is likely the cause for
      Reissner's membrane to collapse post-natally onto the organ of Corti in the
      cochlea. Molecular analyses identified a single integration of ~3 tandemly
      repeated copies of the transgene, a short duplicated segment of chromosome X and
      a 648 kb deletion of chromosome 7(F3). The three known genes (Gpr26, Cpxm2, and
      Chst15) in the deleted region are conserved in mammals and expressed in the wild
      type inner ear during vestibular and cochlea development but are absent in
      homozygous mutant ears. We propose that genes critical for inner ear patterning
      and differentiation are lost at the head bobber locus and are candidate genes for
      human deafness and vestibular disorders.

PMID- 22383093
TI  - Nrf2 links epidermal barrier function with antioxidant defense.
AB  - The skin provides an efficient permeability barrier and protects from microbial
      invasion and oxidative stress. Here, we show that these essential functions are
      linked through the Nrf2 transcription factor. To test the hypothesis that
      activation of Nrf2 provides skin protection under stress conditions, we
      determined the consequences of pharmacological or genetic activation of Nrf2 in
      keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes
      developed epidermal thickening, hyperkeratosis and inflammation resembling
      lamellar ichthyosis. This resulted from upregulation of the cornified envelope
      proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte
      peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in
      keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and
      since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's
      protective function. However, it also caused corneocyte fragility and impaired
      desquamation, followed by alterations in the epidermal lipid barrier,
      inflammation and overexpression of mitogens that induced keratinocyte
      hyperproliferation. These results identify an unexpected role of Nrf2 in
      epidermal barrier function, which needs to be considered for pharmacological use
      of Nrf2 activators.

PMID- 22383095
TI  - The moderating effects of stress and rumination on depressive symptoms in women
      and men.
AB  - Although there is an abundance of research linking stress and rumination to
      depression in women, little is known with respect to the role stress plays in the
      relationship between rumination and depression. Moreover, the role of stress in
      the rumination-depression relationship has not been previously investigated
      separately in women. In the present study, 301 undergraduate women and 109
      undergraduate men were administered a questionnaire battery to assess their
      degrees of stress, depressive symptoms and ruminative tendencies. Individually,
      both stress and rumination scores were found to account for a large proportion of
      variance in depressive symptom scores. The interaction of stress and rumination
      also accounted for a significant proportion of this variance, suggesting a
      significant moderating effect of stress on the rumination-depressive symptom
      relationship in women and men. Furthermore, women and men with the highest
      degrees of stress demonstrated the strongest rumination-depressive symptom
      relationship. However, low-stress women and low-stress men demonstrated divergent
      patterns of relationships. The alternative model of rumination as a moderator of
      the stress-depression relationship likewise supported divergent relationships
      between low-rumination women and low-rumination men in the relationship between
      stress and depression. The implications of these findings regarding vulnerability
      to depressive symptoms are discussed.

PMID- 22383094
TI  - Application of syndemic theory to black men who have sex with men in the
      Multicenter AIDS Cohort Study.
AB  - This study analyzed data from a large prospective epidemiologic cohort study
      among men who have sex with men (MSM), the Multicenter AIDS Cohort Study, to
      assess syndemic relationships among black MSM in the cohort (N = 301). We
      hypothesized that multiple interconnections among psychosocial health conditions
      would be found among these men, defining syndemic conditions. Constituents of
      syndemic conditions measured included reported depression symptoms, sexual
      compulsiveness, substance use, intimate partner violence (IPV), and stress. We
      found significant evidence of syndemics among these black men: depression
      symptoms were independently associated with sexual compulsiveness (odds ratios
      [OR]: 1.88, 95% CI = 1.1, 3.3) and stress (OR: 2.67, 95% CI = 1.5, 4.7); sexual
      compulsiveness was independently associated with stress (OR: 2.04, 95% CI = 1.2,
      3.5); substance misuse was independently associated with IPV (OR: 2.57, 95% CI =
      1.4, 4.8); stress independently was associated with depression symptoms (OR:
      2.67, 95% CI = 1.5, 4.7), sexual compulsiveness (OR: 2.04, 95% CI = 1.2, 3.5) and
      IPV (OR: 2.84, 95% CI = 1.6, 4.9). Moreover, men who reported higher numbers of
      syndemic constituents (three or more conditions) reportedly engaged in more
      unprotected anal intercourse compared to men who had two or fewer health
      conditions (OR: 3.46, 95% CI = 1.4-8.3). Findings support the concept of
      syndemics in black MSM and suggest that syndemic theory may help explain
      complexities that sustain HIV-related sexual transmission behaviors in this
      group.

PMID- 22383096
TI  - YouTube: An emerging tool in anatomy education.
AB  - The use of online social networks in medical education can remodel and enhance
      anatomy teaching and learning; one such network is the video-sharing site
      YouTube. Limited research in the literature exists on the use of YouTube as a
      platform for anatomy education. The aim of this study is to assess student's
      perceptions and patterns of usage of this resource, as well as the effectiveness
      of YouTube videos within a problem-based learning (PBL) curriculum. The study was
      conducted on 91 second-year medical students for whom video links were suggested
      throughout the academic year. In addition, the Human Anatomy Education (HAE)
      Channel was launched on YouTube to support classroom teaching with videos that
      emphasized applied aspects of anatomy. The results demonstrated that 98% of the
      students used YouTube as an online information resource, albeit in different
      frequencies. Out of the 86% who have been to the HAE Channel, 92% agreed/strongly
      agreed that the channel helped them learn anatomy. The study also reports the
      popularity of and awareness about using YouTube as a social network as well as in
      learning. Based on these findings, YouTube can be considered as an effective tool
      to enhance anatomy instruction if the videos are scrutinized, diversified, and
      aimed toward course objectives. Faculty of average computer literacy should be
      enabled to produce videos on their own YouTube channels to support independent
      learning and integration in a PBL curriculum. The methods described for capturing
      and editing the videos can be used as a prototype.

PMID- 22383097
TI  - Disruption of hemochromatosis protein and transferrin receptor 2 causes iron
      induced liver injury in mice.
AB  - Mutations in hemochromatosis protein (HFE) or transferrin receptor 2 (TFR2) cause
      hereditary hemochromatosis (HH) by impeding production of the liver iron
      regulatory hormone, hepcidin (HAMP). This study examined the effects of
      disruption of Hfe or Tfr2, either alone or together, on liver iron loading and
      injury in mouse models of HH. Iron status was determined in Hfe knockout (Hfe(-/
      )), Tfr2 Y245X mutant (Tfr2(mut)), and double-mutant (Hfe(-/-) *Tfr2(mut) ) mice
      by measuring plasma and liver iron levels. Plasma alanine transaminase (ALT)
      activity, liver histology, and collagen deposition were evaluated to assess liver
      injury. Hepatic oxidative stress was assessed by measuring superoxide dismutase
      (SOD) activity and F(2)-isoprostane levels. Gene expression was measured by real
      time polymerase chain reaction. Hfe(-/-) *Tfr2(mut) mice had elevated hepatic
      iron with a periportal distribution and increased plasma iron, transferrin
      saturation, and non-transferrin-bound iron, compared with Hfe(-/-), Tfr2(mut),
      and wild-type (WT) mice. Hamp1 expression was reduced to 40% (Hfe(-/-) and
      Tfr2(mut) ) and 1% (Hfe(-/-) *Tfr2(mut)) of WT values. Hfe(-/-) *Tfr2(mut) mice
      had elevated plasma ALT activity and mild hepatic inflammation with scattered
      aggregates of infiltrating inflammatory cluster of differentiation 45 (CD45)
      positive cells. Increased hepatic hydoxyproline levels as well as Sirius red and
      Masson's Trichrome staining demonstrated advanced portal collagen deposition.
      Hfe(-/-) and Tfr2(mut) mice had less hepatic inflammation and collagen
      deposition. Liver F(2) -isoprostane levels were elevated, and copper/zinc and
      manganese SOD activities decreased in Hfe(-/-) *Tfr2(mut), Tfr2(mut), and Hfe(-/
      ) mice, compared with WT mice. CONCLUSION: Disruption of both Hfe and Tfr2 caused
      more severe hepatic iron overload with more advanced lipid peroxidation,
      inflammation, and portal fibrosis than was observed with the disruption of either
      gene alone. The Hfe(-/-) *Tfr2(mut) mouse model of iron-induced liver injury
      reflects the liver injury phenotype observed in human HH.

PMID- 22383099
TI  - Rare anomaly of great arteries.

PMID- 22383100
TI  - Emergency use of a customized tracheostomy tube for pediatric patients.
AB  - This article describes how to make a customized tracheostomy tube in an emergency
      setting for a pediatric patient. This is particularly critical when a commercial
      customized tracheostomy tube cannot be readily obtained.

PMID- 22383098
TI  - Mechanisms of exercise-induced pulmonary hypertension in patients with cardiac
      septal defects.
AB  - The objective of this study was to investigate mechanisms of exercise-induced
      pulmonary hypertension in patients with congenital cardiac septal defects. This
      was a randomized, placebo controlled, crossover drug trial in a single national
      pediatric cardiology centre that performs congenital cardiac defect surgery.
      There were 14 patients with cardiac septal defects and known exercise-induced
      pulmonary hypertension. The intervention consisted of 50 mg oral sildenafil
      versus placebo. Measurements included supine bicycle exercise echocardiography
      and oxygen uptake. The outcome measure was right-ventricular systolic pressure as
      estimated by Doppler tracings of tricuspid regurgitant jet as well as systolic
      and diastolic longitudinal myocardial velocities by color tissue Doppler
      echocardiography. Sildenafil did not change exercise right-ventricular systolic
      pressure during exercise; however, decreased systemic systolic pressure was seen.
      Enhanced biventricular longitudinal function with sildenafil compared with
      placebo was indicated by greater tissue Doppler velocities and displacement
      measurements during exercise. Finally, a less steep increase of right-ventricular
      pressure during exercise was associated with greater left-ventricular diastolic
      myocardial tissue Doppler velocity. Exercise-induced pulmonary hypertension in
      cardiac septal defects does not seem to have a pulmonary vasoconstrictive
      component, but it may be related to left-ventricular filling pressure.
      Furthermore, sildenafil improved biventricular systolic performance in this
      patient group, possibly related to decreased systemic afterload.

PMID- 22383101
TI  - [Tuberculosis 2012--update of recommendations for the management of tuberculosis
      in Germany].

PMID- 22383102
TI  - [Speech in remembrance of Robert Koch].

PMID- 22383103
TI  - Current concepts for rehabilitation and return to sport after knee articular
      cartilage repair in the athlete.
AB  - Articular cartilage injury is observed with increasing frequency in both elite
      and amateur athletes and results from the significant acute and chronic joint
      stress associated with impact sports. Left untreated, articular cartilage defects
      can lead to chronic joint degeneration and athletic and functional disability.
      Treatment of articular cartilage defects in the athletic population presents a
      therapeutic challenge due to the high mechanical demands of athletic activity.
      Several articular cartilage repair techniques have been shown to successfully
      restore articular cartilage surfaces and allow athletes to return to high-impact
      sports. Postoperative rehabilitation is a critical component of the treatment
      process for athletic articular cartilage injury and should take into
      consideration the biology of the cartilage repair technique, cartilage defect
      characteristics, and each athlete's sport-specific demands to optimize functional
      outcome. Systematic, stepwise rehabilitation with criteria-based progression is
      recommended for an individualized rehabilitation of each athlete not only to
      achieve initial return to sport at the preinjury level but also to continue
      sports participation and reduce risk for reinjury or joint degeneration under the
      high mechanical demands of athletic activity.

PMID- 22383104
TI  - Response shift effects on measuring post-operative quality of life among breast
      cancer patients: a multicenter cohort study.
AB  - PURPOSE: To characterize response shift effects in patients with breast cancer
      (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and
      at the end of the first hospitalization. We used the then-test approach to
      characterize changes in internal standards by calculating the mean difference
      between the then-test (retrospective measure) and pre-test baseline QoL
      assessments. The Ideal Scale Approach was also used to assess changes in
      standards by comparing health and QoL expectancies between baseline and the end
      of the first hospitalization. Successive Comparison Approach was used to assess
      changes in values through the longitudinal assessment of the relative importance
      of EuroQOL dimensions. RESULTS: The results of this study showed that
      recalibration RS effects occurred early after the first hospitalization for 6/15
      dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss,
      diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects).
      Moreover, health and QoL expectancies changed between the baseline and the end of
      the first hospitalization, and changes in values were seen for the self-care and
      usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of
      RS early after the first hospitalization suggests that it needs to be taken into
      account to interpret QoL changes in BC.

PMID- 22383105
TI  - Mortality in nursing home residents without cognitive impairment and its relation
      to self-reported health-related quality of life, sociodemographic factors,
      illness variables and cancer diagnosis: a 5-year follow-up study.
AB  - PURPOSE: It is generally known that health-related quality of life (HRQOL)
      predicts cause-specific mortality. Few studies have explored whether generic self
      reported HRQOL, sociodemographic factors and illness variables are independently
      associated with mortality among cognitively intact nursing home (NH) residents
      with and without cancer. We hypothesized that sociodemographic factors and
      illness variables would be associated with mortality and that HRQOL, measured
      using the SF-36 Health Survey, would predict mortality among NH residents with
      and without cancer. METHODS: We followed a cohort of 227 cognitively intact
      (Clinical Dementia Rating scale score <= 0.5) older residents (60 with cancer and
      167 without) from 30 NH from 2004-2005 to 2010. We collected data by face-to-face
      interview. We obtained sociodemographic variables and medical diagnoses from the
      records. RESULTS: Survival did not differ between residents with and without
      cancer (P = 0.31). Twenty percent of the residents with cancer and 13% without
      cancer were still alive. After adjustment for sociodemographic and illness
      variables, increasing age (P < 0.001), higher education (P = 0.009), comorbidity
      (P = 0.04) and the subdimension physical functioning (P = 0.009) predicted
      mortality. Bodily pain was only marginally associated with mortality (P = 0.08).
      CONCLUSIONS: Independent of cancer, HRQOL and comorbidity predicted mortality
      among NH residents without cognitive impairment.

PMID- 22383106
TI  - Further validation of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in
      the UK veterinary profession: Rasch analysis.
AB  - PURPOSE: To examine the psychometric properties of the 14-item Warwick-Edinburgh
      Mental Well-being Scale (WEMWBS) in the UK veterinary profession by the
      application of Rasch analysis, and to assess the external construct validity of
      the derived interval scale measurements. METHODS: Data sets were derived from two
      independent cross-sectional surveys of the veterinary profession (n = 8,829 and n
      = 1,796). Rasch analysis (n = 500) included response option thresholds ordering,
      tests of fit, differential item functioning, targeting, response dependency, and
      person separation index (PSI). Unidimensionality was evaluated by principal
      component analysis of residuals. The findings were validated across further
      subsamples from both data sets. The external construct validity of the Rasch
      fitting item set was evaluated by associations with other measures of
      psychological health or psychosocial work characteristics. RESULTS: Data for the
      original 14 items deviated significantly from Rasch model expectations (chi
      square = 558.2, df = 112, P = <0.001, PSI = 0.918). A unidimensional 7-item scale
      (Short WEMWBS, SWEMWBS) with acceptable fit to the model (chi-square = 58.8, df =
      56, P = 0.104, PSI = 0.832) was derived by sequential removal of the most
      misfitting items. The external construct validity of SWEMWBS was supported.
      CONCLUSIONS: SWEMWBS has robust interval-level measurement properties which
      support its suitability as an indicator of population mental health and well
      being in this occupational group with elevated suicide risk.

PMID- 22383107
TI  - Behavioral symptoms in community-dwelling elderly Nigerians with dementia, mild
      cognitive impairment, and normal cognition.
AB  - BACKGROUND: Few studies have examined the neuropsychiatric status of patients
      with dementia and cognitive impairment in the developing world despite the fact
      that current demographic trends suggest an urgent need for such studies.
      OBJECTIVE: To assess the level of neuropsychiatric symptoms in community-dwelling
      individuals with dementia, cognitive impairment no dementia and normal cognition.
      METHODS: Subjects were from the Ibadan site of Indianapolis-Ibadan Dementia
      Project with stable diagnoses of normal cognition, cognitive impairment, no
      dementia/mild cognitive impairment (CIND/MCI), and dementia. Informants of
      subjects made ratings on the neuropsychiatric inventory and blessed dementia
      scale; subjects were tested with the mini mental state examination. RESULTS: One
      hundred and eight subjects were included in the analytic sample, 21 were
      cognitively normal, 34 were demented, and 53 were CIND/MCI. The diagnostic groups
      did not differ in age, per cent female, or per cent with any formal education.
      The most frequent symptoms among subjects with CIND/MCI were depression (45.3%),
      apathy (37.7%), night time behavior (28.3%), appetite change (24.5%),
      irritability (22.6%), delusions (22.6%), anxiety (18.9%), and agitation (17.0%).
      Depression was significantly more frequent among the CIND/MCI and dementia
      (44.1%) groups compared with the normal cognition group (9.5%). Distress scores
      were highest for the dementia group, lowest for the normal cognition group, and
      intermediate for the CIND/MCI group. CONCLUSION: Significant neuropsychiatric
      symptomatology and distress are present among cognitively impaired persons in
      this community-based study of older adults in this sub-Saharan African country.
      Programs to assist family members of cognitively impaired and demented persons
      should be created or adapted for use in developing countries.

PMID- 22383108
TI  - Disrupted actin dynamics trigger an increment in the reactive oxygen species
      levels in the Arabidopsis root under salt stress.
AB  - Changes in actin dynamics represent the primary response of the plant cell to
      extracellular signaling. Recent studies have now revealed that actin remodeling
      is involved in abiotic stress tolerance in plants. In our current study, the
      relationship between the changes in actin dynamics and the reactive oxygen
      species (ROS) level at the initial stages of salt stress was investigated in the
      elongation zone of the Arabidopsis root tip. We found that a 200 mM NaCl
      treatment disrupted the dynamics of the actin filaments within 10 min and
      increased the ROS levels in the elongation zone cells of the Arabidopsis root
      tip. We further found that the NADPH oxidase activity inhibitor,
      diphenyleneiodonium, treatment blocked this ROS increase under salt stress
      conditions. The roles of actin dynamics and the NADPH oxidases in ROS generation
      were further analyzed using the actin-specific agents, latrunculin B (Lat-B) and
      jasplakinolide (Jasp), and mutants of Arabidopsis NADPH oxidase AtrbohC. Lat-B
      and Jasp promote actin depolymerization and polymerization, respectively, and
      both were found to enhance the ROS levels following NaCl treatment. However, this
      response was abolished in the atrbohC mutants. Our present results thus
      demonstrate that actin dynamics are involved in regulating the ROS level in
      Arabidopsis root under salt stress conditions. KEY MESSAGE: Salt stress disrupts
      the dynamics of the actin filaments in Arabidopsis in the short term which are
      involved in regulating the ROS levels that arise under salt stress conditions via
      the actions of the AtrbohC.

PMID- 22383109
TI  - Biotech 101: an educational outreach program in genetics and biotechnology.
AB  - Recent advances in research and biotechnology are making genetics and genomics
      increasingly relevant to the lives and health of the general public. For the
      public to make informed healthcare and public policy decisions relating to
      genetic information, there is a need for increased genetic literacy. Biotech 101
      is a free, short-course for the local community introducing participants to
      topics in genetics, genomics, and biotechnology, created at the HudsonAlpha
      Institute for Biotechnology. This study evaluated the effectiveness of Biotech
      101 in increasing the genetic literacy of program participants through pre-and
      post surveys. Genetic literacy was measured through increases in self-perceived
      knowledge for each content area covered through the course and the self-reported
      impact the course had on various aspects of participants' lives. Three hundred
      ninety-two individuals attended Biotech 101 during the first three course
      offerings. Participants reported a significant increase in self-perceived
      knowledge for each content area (p < 0.01). Participants also reported the
      program had high levels of impact on their lives and decision-making, a high
      likelihood for continued self-learning, and overwhelming satisfaction with course
      content and logistics. Biotech 101 is an effective mechanism for impacting
      participants' lives and genetic literacy and serves as a model for other similar
      programs, adding to the currently limited evidence base regarding public
      educational strategies in genetics and biotechnology.

PMID- 22383110
TI  - Tetrakis(methylimidazole) and tetrakis(methylimidazolium) calix[4]arenes:
      competitive anion binding and deprotonation.
AB  - Neutral tetrakis(methylimidazole) (1) and the novel cationic
      tetrakis(methylimidazolium) (2) calixarenes have been prepared and their solid
      state and solution behaviour examined. The neutral imidazole forms a mono
      zwitterion at elevated temperature, a feature that has been observed both in
      solution and in the solid-state. The cationic imidazolium exhibits a range of
      hydrogen bond interactions with anions, with the titration curves upon binding to
      basic anions suggesting sequential binding to both the upper and lower rims.

PMID- 22383111
TI  - Insulin-like growth factor binding protein 7 modulates estrogen-induced
      trophoblast proliferation and invasion in HTR-8 and JEG-3 cells.
AB  - Previous research has reported that IGFBP7 functions as a tumor suppressor gene
      in different tumors, but its role in the trophoblast has not been elucidated. In
      this research, we studied the regulation mechanism of IGFBP7 in trophoblast
      proliferation and invasion in HTR-8 and JEG-3 cell lines. We found that IGFBP7
      was abundantly expressed in normal human syncytiotrophoblast tissue samples but
      that this was lacking in hydatidiform moles. The proliferation and invasion
      capacities of HTR-8 and JEG-3 cells were significantly inhibited by recombinant
      IGFBP7. Estrogen (E2) stimulated the expression of IGFBP7 at a concentration of 5
      10 ng/mL. This stimulation was inhibited by the estrogen receptor antagonist
      Fulvestrant (ICI182.780) and a TGFbeta-neutralizing antibody. In conclusion, our
      data reveals that estrogen stimulates the expression of IGFBP7 through estrogen
      receptors and TGFbeta. The expression of IGFBP7 could be stimulated by TGFbeta in
      a dose-dependent manner and inhibited by IFNgamma in HTR-8 and JEG-3 cells.
      IGFBP7 could also inhibit the phosphorylation of ERK and the expression of PCNA,
      MMP2 and MMP9 in HTR-8 and JEG-3 cells. These findings suggest that IGFBP7 is a
      key regulator of E2-induced trophoblast proliferation and invasion.

PMID- 22383112
TI  - Structural insights into genetic variants of Na(+)/glucose cotransporter SGLT1
      causing glucose-galactose malabsorption: vSGLT as a model structure.
AB  - Current advances in structural biology provide valuable insights into structure
      function relationship of membrane transporters by solving crystal structures of
      bacterial homologs of human transporters. Therefore, scientists consider
      bacterial transporters as useful structural models for designing of drugs
      targeted in human diseases. The functional homology between Vibrio
      parahaemolyticus Na(+)/galactose transporter (vSGLT) and Na(+)/glucose
      cotransporter SGLT1 has been well established a decade ago. Now the crystal
      structure of vSGLT is considered quite valuable in explaining not only the
      cotransport mechanisms, but it also acts as a representative protein in
      understanding the protein stability and amino acid interactions within the core
      structure. We investigated the molecular mechanisms of genetic variations in
      SGLT1 that cause glucose-galactose malabsorption (GGM) defects using the crystal
      structure of vSGLT as a model sugar transporter. Our in silico mutagenesis and
      modeling analysis suggest that the GGM genetic variations lead to conformational
      changes either by structure destabilization or by formation of unnecessary
      interaction within the core structure of SGLT1 thereby explaining the genetic
      defects in Na(+) dependent sugar translocation across the cell membrane.

PMID- 22383113
TI  - Synthesis and unexpected coordination of a silicon(II)-based SiCSi pincerlike
      arene to palladium.

PMID- 22383114
TI  - Screening candidate anticancer drugs for brain tumor chemotherapy:
      pharmacokinetic-driven approach for a series of (E)-N-(substituted aryl)-3
      (substituted phenyl)propenamide analogues.
AB  - A pharmacokinetic [PK]-driven screening process was implemented to select new
      agents for brain tumor chemotherapy from a series of low molecular weight
      anticancer agents [ON27x] that consisted of 141 compounds. The screening
      procedures involved a combination of in silico, in vitro and in vivo mouse
      studies that were cast into a pipeline of tier 1 and tier 2 failures that
      resulted in a final investigation of 2 analogues in brain tumor-bearing mice.
      Tier 1 failures included agents with a molecular weight of > 450 Da, a predicted
      log P (log P) of either <2 or > 3.5, and a cytotoxicity IC(50) value of > 2 uM.
      Next, 18 compounds underwent cassette dosing studies in normal mice that
      identified compounds with high systemic clearance, and low blood-brain barrier
      [BBB] penetration. These indices along with a derived parameter, referred to as
      the brain exposure index, comprised tier 2 failures that led to the
      administration of 2 compounds [ON27570, ON27740] as single agents [discrete
      dosing] to mice bearing intracerebral tumors. Comparison of ON27570's resultant
      PK parameters to those obtained in the cassette dosing format suggested a drug
      drug interaction most likely at the level of BBB transport, and prompted the use
      of the in vitro MDCK-MDR1 transport model to help assess the nature of the
      discrepancy. Overall, the approach was able to identify candidate compounds with
      suitable PK characteristics yet further revisions to the method, such as the use
      of in vitro metabolism and transport assays, may improve the PK-directed approach
      to identify efficacious agents for brain tumor chemotherapy.

PMID- 22383115
TI  - Estimation of self-diffusion coefficients of small penetrants in semicrystalline
      polymers using single-sided NMR.
AB  - A simple and fast way to measure proton self-diffusion coefficients of small
      penetrant molecules in semicrystalline polymers is introduced. The approach takes
      advantage of the strong static gradient of a mobile single-sided NMR sensor and
      it is demonstrated on PE samples with varying degrees of crystallinity fully
      saturated in either toluene or n-hexane. The self-diffusion coefficients were
      measured using the gradient stimulated echo sequence appended with a CPMG. It is
      also shown for the first time, with demonstration on PE plates several millimeter
      thick with different aging histories, that one-dimensional profiles of self
      diffusion coefficients as a function of depth can be easily obtained.

PMID- 22383116
TI  - [Reality of healthcare access for migrant children in Mayotte].
AB  - The implementation of the social security system in 2005 in Mayotte has resulted
      in the end of free healthcare for all non-affiliated residents, primarily
      Comorians, due to the absence of the State Medical Aid (AME) in this department.
      Doctors of the World France opened a paediatric clinic in December 2009. The
      sociomedical data were collected during 5286 consultations in 2010. Analysis of
      these data demonstrates a link between access to healthcare for children and the
      residential status of their parents. The analysis concerns 2,350 patients met
      during consultations held by Doctors of the World France in Mayotte in 2010. The
      data have been electronically recorded and analysed by the Sphinx software. The
      results show that there are several obstacles to healthcare resulting in non
      attendance. This situation is made worse if one of the parents has an irregular
      residential status and all the more so if both the parents have an irregular
      status. Affiliation to the social security system, however, improves the
      situation. The results show a delay in accessing healthcare, a poor vaccination
      programme and disturbing data on severe acute malnutrition. The specific
      healthcare measures in Mayotte do not respect the International Convention on the
      Rights of the Child. Direct affiliation to the social security system for
      children would entail a reduction in health insecurity for the children of
      parents with irregular residential status. It would also be necessary to reduce
      the factors that provoke fear of displacement, which would facilitate physical
      access to consultations.

PMID- 22383117
TI  - Modeling seasonal rabies epidemics in China.
AB  - Human rabies, an infection of the nervous system, is a major public-health
      problem in China. In the last 60 years (1950-2010) there had been 124,255
      reported human rabies cases, an average of 2,037 cases per year. However, the
      factors and mechanisms behind the persistence and prevalence of human rabies have
      not become well understood. The monthly data of human rabies cases reported by
      the Chinese Ministry of Health exhibits a periodic pattern on an annual base. The
      cases in the summer and autumn are significantly higher than in the spring and
      winter. Based on this observation, we propose a susceptible, exposed, infectious,
      and recovered (SEIRS) model with periodic transmission rates to investigate the
      seasonal rabies epidemics. We evaluate the basic reproduction number R (0),
      analyze the dynamical behavior of the model, and use the model to simulate the
      monthly data of human rabies cases reported by the Chinese Ministry of Health. We
      also carry out some sensitivity analysis of the basic reproduction number R (0)
      in terms of various model parameters. Moreover, we demonstrate that it is more
      reasonable to regard R (0) rather than the average basic reproduction number
      [Formula: see text] or the basic reproduction number [Formula: see text] of the
      corresponding autonomous system as a threshold for the disease. Finally, our
      studies show that human rabies in China can be controlled by reducing the birth
      rate of dogs, increasing the immunization rate of dogs, enhancing public
      education and awareness about rabies, and strengthening supervision of pupils and
      children in the summer and autumn.

PMID- 22383118
TI  - Pegylated interferon for chronic hepatitis C in children affects growth and body
      composition: results from the pediatric study of hepatitis C (PEDS-C) trial.
AB  - Weight loss and changes in growth are noted in children treated with interferon
      alpha (IFN-alpha). The aim of this study was to prospectively determine changes
      in weight, height, body mass index (BMI), and body composition during and after
      treatment of children with hepatitis C virus (HCV). Children treated with
      pegylated interferon alpha-2a (Peg-IFN-alpha2a) +/- ribavirin in the Pediatric
      Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual
      energy X-ray absorptiometry scan, as well as dietary and activity assessments
      during and after treatment. One hundred and fourteen (55% male) children, with a
      mean age of 11 +/- 3 years, were randomized, and 107 received treatment for at
      least 24 weeks. Subjects were divided into three groups according to duration of
      treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to
      0.50 z score were observed for weight, height, and BMI while on therapy among all
      groups (P <= 0.01, compared to baseline). In the group treated for 48 weeks, 29
      (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ)
      score. Though weight-for-age and BMI z scores returned to baseline after
      cessation of therapy, mean HAZ score was slower to rebound, still lower than
      baseline at 96 weeks post-therapy for the long-treatment duration group (P =
      0.03) and lower than baseline in most children treated for 48 weeks. Percent body
      fat, fat-free mass z scores, and triceps skinfold z scores decreased with
      therapy. Dietary energy intake and levels of physical activity did not change
      during treatment. CONCLUSIONS: Peg-IFN-alpha2a was associated with significant
      changes in body weight, linear growth, BMI, and body composition in children.
      These effects were generally reversible with cessation of therapy, although HAZ
      scores had not returned to baseline after 2 years of observation in many. Longer
      term growth data are needed among children treated for chronic HCV.

PMID- 22383119
TI  - Population structure and diversity of phenazine-1-carboxylic acid producing
      fluorescent Pseudomonas spp. from dryland cereal fields of central Washington
      State (USA).
AB  - Certain strains of the rhizosphere bacterium Pseudomonas fluorescens contain the
      phenazine biosynthesis operon (phzABCDEFG) and produce redox-active phenazine
      antibiotics that suppress a wide variety of soilborne plant pathogens. In 2007
      and 2008, we isolated 412 phenazine-producing (Phz(+)) fluorescent Pseudomonas
      strains from roots of dryland wheat and barley grown in the low-precipitation
      region (<350 mm annual precipitation) of central Washington State. Based on
      results of BOX-PCR genomic fingerprinting analysis, these isolates, as well as
      the model biocontrol Phz(+) strain P. fluorescens 2-79, were assigned to 31
      distinct genotypes separated into four clusters. All of the isolates exhibited
      high 16S rDNA sequence similarity to members of the P. fluorescens species
      complex including Pseudomonas orientalis, Pseudomonas gessardii, Pseudomonas
      libanensis, and Pseudomonas synxantha. Further recA-based sequence analyses
      revealed that the majority of new Phz(+) isolates (386 of 413) form a clade
      distinctly separated from P. fluorescens 2-79. Analysis of phzF alleles, however,
      revealed that the majority of those isolates (280 of 386) carried phenazine
      biosynthesis genes similar to those of P. fluorescens 2-79. phzF-based analyses
      also revealed that phenazine genes were under purifying selection and showed
      evidence of intracluster recombination. Phenotypic analyses using Biolog
      substrate utilization and observations of phenazine-1-carboxylic acid production
      showed considerable variability amongst members of all four clusters.
      Biodiversity indices indicated significant differences in diversity and evenness
      between the sampled sites. In summary, this study revealed a genotypically and
      phenotypically diverse group of phenazine producers with a population structure
      not seen before in indigenous rhizosphere-inhabiting Phz(+) Pseudomonas spp.

PMID- 22383120
TI  - Sequence analyses of type IV pili from Vibrio cholerae, Vibrio parahaemolyticus,
      and Vibrio vulnificus.
AB  - Bacterial surface structures called pili have been studied extensively for their
      role as possible colonization factors. Most sequenced Vibrio genomes predict a
      variety of pili genes in these organisms, including several types of type IV
      pili. In particular, the mannose-sensitive hemagglutinin (MSHA) and the PilA
      pili, also known as the chitin-regulated pilus (ChiRP), are type IVa pili
      commonly found in Vibrio genomes and have been shown to play a role in the
      colonization of Vibrio species in the environment and/or host tissue. Here, we
      report sequence comparisons of two type IVa pilin subunit genes, mshA and pilA,
      and their corresponding amino acid sequences, for several strains from the three
      main human pathogenic Vibrio species, V. cholerae, V. parahaemolyticus, and V.
      vulnificus. We identified specific groupings of these two genes in V. cholerae,
      whereas V. parahaemolyticus and V. vulnificus strains had no apparent allelic
      clusters, and these genes were strikingly divergent. These results were compared
      with other genes from the MSHA and PilA operons as well as another Vibrio pili
      from the type IVb group, the toxin co-regulated pilus (TCP) from V. cholerae. Our
      data suggest that a selective pressure exists to cause these strains to vary
      their MSHA and PilA pilin subunits. Interestingly, V. cholerae strains possessing
      TCP have the same allele for both mshA and pilA. In contrast, V. cholerae
      isolates without TCP have polymorphisms in their mshA and pilA sequences similar
      to what was observed for both V. parahaemolyticus and V. vulnificus. This data
      suggests a possible linkage between host interactions and maintaining a highly
      conserved type IV pili sequence in V. cholerae. Although the mechanism underlying
      this intriguing diversity has yet to be elucidated, our analyses are an important
      first step towards gaining insights into the various aspects of Vibrio ecology.

PMID- 22383121
TI  - Methanogen colonisation does not significantly alter acetogen diversity in lambs
      isolated 17 h after birth and raised aseptically.
AB  - Reductive acetogenesis is not competitive with methanogenesis in adult ruminants,
      whereas acetogenic bacteria are the dominant hydrogenotrophs in the early rumen
      microbiota. The ecology of hydrogenotrophs in the developing rumen was
      investigated using young lambs, raised in sterile isolators, and conventional
      adult sheep. Two lambs were born naturally, left with their dams for 17 h and
      then placed into a sterile isolator and reared aseptically. They were inoculated
      with cellulolytic bacteria and later with Methanobrevibacter sp. 87.7 to
      investigate the effect of methanogen establishment on the rumen acetogen
      population since they lacked cultivable representatives of methanogens. Putative
      acetogens were investigated by acetyl-CoA synthase and formyltetrahydrofolate
      synthetase gene analysis and methanogens by methyl coenzyme reductase A gene
      analysis. Unexpectedly, a low abundant but diverse population of methanogens
      (predominantly Methanobrevibacter spp.) was identified in isolated lambs pre
      inoculation with Mbb. sp 87.7, which was similar to the community structure in
      conventional sheep. In contrast, potential acetogen diversity in isolated lambs
      and conventional sheep was different. Potential acetogens affiliated between the
      Lachnospiraceae and Clostridiaceae in conventional sheep  and with the Blautia
      genus and the Lachnospiraceae in isolated lambs. The establishment of Mbb. sp.
      87.7 (1,000-fold increase in methanogens) did not substantially affect acetogen
      diversity.

PMID- 22383122
TI  - A comparison of BOX-PCR and pulsed-field gel electrophoresis to determine genetic
      relatedness of enterococci from different environments.
AB  - Genetic relatedness of enterococci from poultry litter to enterococci from nearby
      surface water and groundwater in the Lower Fraser Valley regions of British
      Columbia, Canada was determined. A new automated BOX-PCR and Pulsed-Field Gel
      Electrophoresis (PFGE) were used to subtype enterococcal isolates from broiler
      and layer litter and surface and groundwater. All surface water samples (n = 12)
      were positive for enterococci, as were 11% (3/28) of groundwater samples.
      Enterococcus faecium (n = 90) was isolated from all sources, while Enterococcus
      faecalis (n = 59) was isolated from all sources except layer litter. The majority
      of E. faecalis originated from broiler litter (28/59; 47.5%) while the majority
      of E. faecium were isolated from layer litter (29/90; 32.2%). E. faecalis grouped
      primarily by source using BOX-PCR. Isolates from water samples were dispersed
      more frequently among PFGE groups containing isolates from poultry litter. E.
      faecium strains were genetically diverse as overall clustering was independent of
      source by both molecular methods. Subgroups of E. faecium isolates based upon
      source (layer litter) were present in BOX-PCR groups. Three individual E.
      faecalis groups and two individual E. faecium groups were 100% similar using BOX
      PCR; only one instance of 100% similarity among isolates using PFGE was observed.
      Although enterococci from litter and water sources were grouped together using
      BOX-PCR and PFGE, isolates originating from water could not be definitively
      identified as originating from poultry litter. Automation of BOX-PCR amplicon
      separation and visualization increased the reproducibility and standardization of
      subtyping using this procedure.

PMID- 22383123
TI  - Oxidative Heck arylation for the stereoselective synthesis of tetrasubstituted
      olefins using nitroxides as oxidants.

PMID- 22383124
TI  - Near-peer teaching in an anatomy course with a low faculty-to-student ratio.
AB  - Near-peer teaching is an educational format which utilizes tutors who are more
      advanced in a curriculum's content to supervise students' activities and to act
      as instructors in laboratory settings. This format is often used in anatomy
      laboratory courses. The goal of the present study is to describe the design and
      implementation of near-peer teaching in an anatomy course and to evaluate
      students' perceptions of the program. A total of 700 students were registered for
      this anatomy course which employed near-peer instructors. Of enrolled students,
      558 (79.7%) agreed to participate in this study. In general, the practical
      section (e.g., the clinical hour, image-based anatomy session, and gross anatomy
      laboratory) of the course was viewed more favorably compared to the theory
      section (54.8%, n = 306), with dissection and prosection in the laboratory rated
      as the most valued experiences (34.9%, n = 195). Near-peer teaching is a viable
      option that satisfies the demands of modern curricula using small groups. This
      format stimulates learning within courses that have large numbers of students and
      low faculty-to-student ratios.

PMID- 22383125
TI  - Occipital nerve block is effective in craniofacial neuralgias but not in
      idiopathic persistent facial pain.
AB  - Occipital nerve block (ONB) has been used in several primary headache syndromes
      with good results. Information on its effects in facial pain is sparse. In this
      chart review, the efficacy of ONB using lidocaine and dexamethasone was evaluated
      in 20 patients with craniofacial pain syndromes comprising 8 patients with
      trigeminal neuralgia, 6 with trigeminal neuropathic pain, 5 with persistent
      idiopathic facial pain and 1 with occipital neuralgia. Response was defined as an
      at least 50% reduction of original pain. Mean response rate was 55% with greatest
      efficacy in trigeminal (75%) and occipital neuralgia (100%) and less efficacy in
      trigeminal neuropathic pain (50%) and persistent idiopathic facial pain (20%).
      The effects lasted for an average of 27 days with sustained benefits for 69, 77
      and 107 days in three patients. Side effects were reported in 50%, albeit
      transient and mild in nature. ONBs are effective in trigeminal pain involving the
      second and third branch and seem to be most effective in craniofacial neuralgias.
      They should be considered in facial pain before more invasive approaches, such as
      thermocoagulation or vascular decompression, are performed, given that side
      effects are mild and the procedure is minimally invasive.

PMID- 22383126
TI  - 'Hearts and bones': the ups and downs of 'plasticity' in stem cell biology.
AB  - More than a decade ago, 'plasticity' suddenly became a 'fashionable' topic with
      overemphasized implications for regenerative medicine. The concept of
      'plasticity' is supported by old transplantation work, at least for embryonic
      cells, and metaplasia is a classic example of plasticity observed in patients.
      Nevertheless, the publication of a series of papers showing rare conversion of a
      given cell type into another unrelated cell raised the possibility of using any
      unaffected tissue to create at will new cells to replace a different failing
      tissue or organ. This resulted in disingenuous interpretations and a reason not
      to fund anymore research on embryonic stem cells (ESc). Moreover, many papers on
      plasticity were difficult to reproduce and thus questioned; raising issues about
      plasticity as a technical artefact or a consequence of rare spontaneous cells
      fusion. More recently, reprogramming adult differentiated cells to a pluripotent
      state (iPS) became possible, and later, one type of differentiated cell could be
      directly reprogrammed into another (e.g. fibroblasts into neurons) without
      reverting to pluripotency. Although the latter results from different and more
      robust experimental protocols, these phenomena also exemplify 'plasticity'. In
      this review, we want to place 'plasticity' in a historical perspective still
      taking into account ethical and political implications.

PMID- 22383127
TI  - Markers of platelet apoptosis: methodology and applications.
AB  - Apoptosis, or programmed cell death, is a physiological mechanism that serves for
      controlled deletion of damaged cells. While long attributed exclusively to
      nucleated cells, over recent years it has been recognized that apoptosis also
      occurs in anucleate platelets. We describe here experiences of determining
      markers of apoptosis in human platelets treated in vitro with pro-apoptotic
      chemical and physical stimuli. These include depolarization of mitochondrial
      inner membrane, cytochrome c release, expression of pro-apoptotic and anti
      apoptotic proteins of Bcl-2 family, activation of apoptosis executioner caspase
      3, exposure of phosphatidylserine, platelet shrinkage, fragmentation to
      microparticles, blebbing and filopod extrusion on the platelet surface. These
      assays serve to characterize platelet apoptosis in different cellular
      compartments (mitochondria, cytosol and plasma membrane) and at the whole-cell
      level. Methods commonly employed in studies of platelet apoptosis markers include
      flow cytometry, Western blot analysis and electron microscopy. An integrated
      methodological approach, based on determination of different platelet apoptosis
      markers, represents a useful tool for examining platelet apoptosis in various
      physiological and pathological settings.

PMID- 22383130
TI  - Step frequency and lower extremity loading during running.
AB  - The purpose of the present study was to ascertain whether increase in step
      frequency at a given velocity during running reduces the lower extremity loading
      variables, which is associated with tibial stress fracture in runner. We
      hypothesized that the lower extremity loading variables at a given speed would be
      minimized at around +15% f step. 10 male subjects were asked to run at 2.5 m/s on
      a treadmill-mounted force platform. 5 step frequencies were controlled using a
      metronome: the preferred, below preferred (-15 and -30%) and above preferred (+15
      and +30%). From the vertical ground reaction force, we measured following lower
      extremity loading variables; vertical impact peak (VIP), vertical instantaneous
      loading rate (VILR) and vertical average loading rate (VALR). We found that there
      were significant differences in lower extremity loading variables among 5 step
      frequency conditions. Furthermore, quadratic regression analyses revealed that
      the minimum loading variable frequencies were 17.25, 17.55, and 18.07% of
      preferred step frequency for VIP, VILR and VIAR, respectively. Thus, adopting a
      step frequency greater than one's preferred may be practical in reducing the risk
      of developing a tibial stress fracture by decreasing lower extremity loading
      variables.

PMID- 22383129
TI  - Potential therapeutic applications of phosphodiesterase inhibition in prostate
      cancer.
AB  - OBJECTIVE: Phosphodiesterases (PDEs) play a role in controlling cyclic nucleotide
      action, including cyclic guanosine monophosphate (cGMP). Previous studies have
      ascribed a protective role of cGMP signaling on hypoxia-mediated cancer
      progression. Herein, we determine their potential role in hypoxia-mediated
      chemoresistance and immune escape. MATERIALS AND METHODS: Phosphodiesterase
      assays were used to measure PDE activity in prostate cancer cell lines (DU145,
      PC3). Immunoblots were performed to determine the presence of PDEs in human
      prostate tissue samples. The effect of PDE inhibition on hypoxia-induced
      chemoresistance (compared to normoxic controls, 20% O2) was determined using
      clonogenic assays. Flow cytometry was used to determine the effects of PDE
      inhibition on surface MHC class I-related chain A (MICA), a natural killer (NK)
      cell-activating ligand. A mouse model was used to evaluate the in vivo effects of
      PDE inhibition on the growth of human prostate cancer cells. RESULTS: PDE5 and
      PDE11 were the most prominent PDEs in the cell lines, representing between 86 and
      95% of the total cGMP-specific PDE activity. Treatment of DU-145 cells with a PDE
      inhibitor significantly reduced the hypoxia-associated acquisition of resistance
      to doxorubicin, with a mean 51% reduction in surviving fraction compared to
      controls (p < 0.001, ANOVA). As well, PDE inhibition completely reversed (p =
      0.02, ANOVA) hypoxia-induced shedding of the immune stimulatory molecule, MICA,
      and attenuated the growth of human prostate tumor xenografts in an NK cell
      competent murine model (p = 0.03, Wilcoxon, Mann-Whitney). CONCLUSIONS: These
      results suggest a rationale for future studies on the potential therapeutic
      applications of PDE inhibitors in men with prostate cancer.

PMID- 22383131
TI  - The effect of starting or stopping skin cooling on the thermoregulatory responses
      during leg exercise in humans.
AB  - To assess the effects of starting or stopping leg cooling on the thermoregulatory
      responses during exercise, 60 min of cycling exercise at 30% of maximal oxygen
      uptake was performed under 4 conditions using tube trouser perfused with water at
      10  degrees C; no leg cooling (NC), starting of leg cooling after 30 min of
      exercise (delayed cooling, DC), continuous leg cooling (CC), and stopping of
      continuous leg cooling after 30 min of exercise (SC) at an environmental
      temperature of 28.5  degrees C. During exercise under the DC conditions, an
      instantaneous increase in the esophageal temperature (Tes), a suppression of the
      cutaneous vascular conductance at the forearm (%CVC), and a decrease in the mean
      skin temperature (Tsk) were observed after leg cooling. The total sweat loss
      (Deltam sw,tot) was lower under the DC than the NC condition. In the SC study,
      however, the Tes remained constant, while the %CVC increased gradually after leg
      cooling was stopped, and the Deltam sw,tot was greater than that under the CC
      condition. These results suggest that during exercise, rapid skin cooling of the
      leg may cause an increase in core temperature, while also enhancing thermal
      stress. However, stopping skin cooling did not significantly affect the core
      temperature long-term, because the skin blood flow and sweat rate subsequently
      increased.

PMID- 22383135
TI  - Chondral lesion of the patella.

PMID- 22383136
TI  - Sample sizes for trials involving multiple correlated must-win comparisons.
AB  - In Clinical trials involving multiple comparisons of interest, the importance of
      controlling the trial Type I error is well-understood and well-documented.
      Moreover, when these comparisons are themselves correlated, methodologies exist
      for accounting for the correlation in the trial design, when calculating the
      trial significance levels. However, less well-documented is the fact that there
      are some circumstances where multiple comparisons affect the Type II error rather
      than the Type I error, and failure to account for this, can result in a reduction
      in the overall trial power. In this paper, we describe sample size calculations
      for clinical trials involving multiple correlated comparisons, where all the
      comparisons must be statistically significant for the trial to provide evidence
      of effect, and show how such calculations have to account for multiplicity in the
      Type II error. For the situation of two comparisons, we provide a result which
      assumes a bivariate Normal distribution. For the general case of two or more
      comparisons we provide a solution using inflation factors to increase the sample
      size relative to the case of a single outcome. We begin with a simple case of two
      comparisons assuming a bivariate Normal distribution, show how to factor in
      correlation between comparisons and then generalise our findings to situations
      with two or more comparisons. These methods are easy to apply, and we demonstrate
      how accounting for the multiplicity in the Type II error leads, at most, to
      modest increases in the sample size.

PMID- 22383132
TI  - Assessment of dementia risk in aging adults using both FDG-PET and FDDNP-PET
      imaging.
AB  - BACKGROUND: In a previous study, positron emission tomography (PET) with 2-(1-{6
      [(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP),
      a molecule that binds to plaques and tangles in vitro, identified three subgroups
      of non-demented subjects according to FDDNP binding patterns: low global (LG)
      binding; high frontal, parietal, medial temporal binding (HF/PA); and high medial
      and lateral temporal and posterior cingulate (HT/PC) binding. In this follow-up
      investigation, we compared 2-deoxy-2-[F-18]fluoro- d-glucose (FDG)-PET cerebral
      metabolic patterns in the three FDDNP-PET binding subgroups. METHODS: Fifty-four
      subjects with normal aging (N = 28) or amnestic forms of mild cognitive
      impairment (N = 26) underwent FDDNP-PET and FDG-PET scanning. Subjects in the LG,
      HF/PA, and HT/PC FDDNP subgroups were compared according to visual ratings,
      statistical parametric mapping, and automated region of interest analyses of
      their FDG-PET data. RESULTS: The FDDNP-PET subgroups demonstrated different
      glucose metabolic patterns according to visual ratings, region of interest, and
      statistical parametric mapping analyses of FDG-PET data. The LG FDDNP subgroup
      showed no areas of significant hypometabolism relative to the other subgroups and
      had low Alzheimer's disease risk by FDG-PET standards. The HF/PA FDDNP subgroup
      demonstrated hypometabolism in bilateral inferior parietal/parietotemporal,
      bilateral posterior cingulate, perisylvian, mid-temporal gyrus, and dorsolateral
      prefrontal regions, which is a pattern suggestive of high Alzheimer's disease
      risk. The HT/PC FDDNP subgroup demonstrated heterogeneous FDG-PET patterns with
      predominant anterior frontal and anterior temporal hypometabolism, suggestive of
      mixed etiologies, including fronto-temporal dementia risk. CONCLUSIONS: The FDG
      PET data provided independent validation that different patterns of FDDNP-PET
      binding in non-demented individuals may be associated with differential dementia
      risk.

PMID- 22383138
TI  - Switching control of an essential gene for reprogramming of cellular phenotypes
      in Escherichia coli.
AB  - Biological systems designs require various dynamic controllers capable of
      modulating cellular phenotypes to adapt to changing environments. Cellular
      phenotypes are simultaneously affected by combinations of multiple genes that are
      controlled by global regulators. However, it is difficult to intentionally
      control the expression of these global regulators dynamically because they are
      essential for cell survival and are involved in regulatory networks clustered in
      operons. Here, we designed a platform that allows dynamic modulation of the
      expression of an essential gene. Using this system, comprising of on/off switches
      that respond to an extracellular stimulus, we successfully demonstrated the
      switching control of the expression of fusA encoding elongation factor G (EF-G).
      An additional control module in this system that responds to changed external
      signals was shown to provide the capacity to "switch gears" and reprogram
      cellular phenotypes with desired timing.

PMID- 22383139
TI  - Association of genetic variations of PRDM16 with metabolic syndrome in a general
      Xinjiang Uygur population.

PMID- 22383140
TI  - Assessment of microcystin distribution and biomagnification in tissues of aquatic
      food web compartments from a shallow lake and evaluation of potential risks to
      public health.
AB  - The objectives of this study were: (1) to examine the distribution and
      bioaccumulation of microcystins in the main components of the food web
      (phytoplankton, zooplankton, crayfish, shrimp, mussel, snail, fish, frog) of Lake
      Pamvotis (NW Greece), (2) to investigate the possibility of microcystin
      biomagnification and (3) to evaluate the potential threat of the contaminated
      aquatic organisms to human health. Significant microcystin concentrations were
      detected in all the aquatic organisms during two different periods, with the
      higher concentrations observed in phytoplankton and the lower in fish species and
      frogs. This is the first study reporting microcystin accumulation in the body of
      the freshwater shrimp Atyaephyra desmsaresti, in the brain of the fish species
      common carp (Cyprinus carpio) and in the skin of the frog Rana epirotica.
      Although there was no evidence for microcystin biomagnification, the fact that
      microcystins were found in lake water and in the tissues of aquatic organisms,
      suggests that serious risks to animal and public health are possible to occur. In
      addition, it is likely to be unsafe to consume aquatic species harvested in Lake
      Pamvotis due to the high-concentrations of accumulated microcystins.

PMID- 22383141
TI  - Using sets of behavioral biomarkers to assess short-term effects of pesticide: a
      study case with endosulfan on frog tadpoles.
AB  - Pesticides and other chemicals often have detrimental effects at environmental
      concentrations. Many amphibian species are particularly threatened because of
      their susceptibility but also because wetlands are often polluted. Behavioral
      assessments of toxicity have the advantage of showing sublethal effects but
      quantitative measures at varied scales of integrations are rarely considered
      together. In this study, we aimed at showing that these behavioral endpoints
      could be differently affected across time and concentrations, and be biomarkers
      of toxicity. To this end, we tested the effects of an organochlorine pesticide
      (endosulfan) on amphibians during a standard 96 h test. We evaluated possible lag
      effects in continuing the analyses after removal of the pesticide. The study was
      based on 240 tadpoles (4 pesticide treatments: 0.4, 3, 22, and 282 MUg/l, 1
      control and 1 solvent-control). Abnormal behaviors such as lying and swirling
      rapidly were exhibited only in the presence of the pesticide. Essential functions
      such as breathing and feeding were deeply affected by the pesticide: contaminated
      tadpoles breathed and fed less than control tadpoles. They also moved less and
      occupied a more central position in the aquariums in the presence of the
      pesticide. A higher mortality was only found at the highest concentration. These
      results suggest that endosulfan is toxic to amphibians at environmental
      concentrations. Behavioral markers showed potential as early warning systems.
      They should thus be used in complement to other markers to detect sublethal
      effects only a few days after application of the pesticide and at concentrations
      where mortality does not occur.

PMID- 22383142
TI  - Obesity as malnutrition: the role of capitalism in the obesity global epidemic.
AB  - The global obesity epidemic remains poorly understood, partly because it has
      emerged alongside persisting under-nutrition in many populations. At an abstract
      level, obesity develops from exposure to the "obesogenic niche," comprising
      diverse factors predisposing to weight gain. This article first explores how
      susceptibility to the obesogenic niche is influenced by developmental and life
      history experience. Human growth is sensitive to early-life ecological
      conditions, under the transducing effect of maternal phenotype. Such plasticity
      is associated with subsequent variability in body composition and metabolism,
      impacting susceptibility to the obesogenic niche, albeit with heterogeneity
      across populations. Both nutritional constraint and nutritional excess during
      early life are associated with variability in relevant molecular pathways. The
      article then considers the fundamental contribution of capitalist economics to
      population under-nutrition and over-nutrition. Historically, capitalism
      contributed to the under-nutrition of many populations through demand for cheap
      labor. As the limiting factor for economic growth switched to consumption,
      capitalism has increasingly driven consumer behavior inducing widespread over
      nutrition. In populations undergoing nutritional transition, many individuals
      encounter both under- and over-nutrition within the life course, elevating both
      susceptibility and exposure to the obesogenic niche. The interactions between
      global economic forces and nutritional shifts are distributed across generations,
      and are strongly transduced by maternal effects. The structural connections
      between undernourished and overnourished worldwide and between under- and over
      nutrition within individual life-courses highlight the central role of capitalist
      economics in the global obesity epidemic. Prevention policies targeting
      individual behavior have proved ineffective and economic policies are arguably
      the optimal target for intervention.

PMID- 22383143
TI  - Cardiology in Denmark.

PMID- 22383144
TI  - Good publishing practice.

PMID- 22383145
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology National Cardiovascular Journals.
AB  - Disclosure of potential conflicts of interest (COIs) is used by biomedical
      journals to guarantee credibility and transparency of the scientific process.
      Conflict of interest disclosure, however, is not systematically nor consistently
      dealt with by journals. Recent joint editorial efforts paved the way towards the
      implementation of uniform vehicles for COI disclosure. This paper provides a
      comprehensive editorial perspective on classical COI-related issues. New insights
      into the current COI policies and practices among European Society of Cardiology
      National Cardiovascular Journals, as derived from a cross-sectional survey using
      a standardized questionnaire, are discussed.

PMID- 22383146
TI  - Relations between professional medical associations and the health-care industry,
      concerning scientific communication and continuing medical education: a Policy
      Statement from the European Society of Cardiology.
AB  - Physicians have an ethical duty to keep up-to-date with current knowledge.
      Professional medical associations such as the European Society of Cardiology
      (ESC) support these obligations. In Europe, the costs of continuing medical
      education (CME) are insufficiently supported from governments and employers;
      however, medical associations have been criticized for accepting alternative
      financial support from industry. Medical education and training in research
      include learning how to assess the quality and reliability of any information.
      There is some risk of bias in any form of scientific communication including
      intellectual, professional, and financial and it is essential that in particular,
      the latter must be acknowledged by full disclosure. It is essential that there is
      strong collaboration between basic and clinical researchers from academic
      institutions on the one hand, with engineers and scientists from the research
      divisions of device and pharmaceutical companies on the other. This is vital so
      that new diagnostic methods and treatments are developed. Promotion of advances
      by industry may accelerate their implementation into clinical practice.
      Universities now frequently exhort their academic staff to protect their
      intellectual property or commercialize their research. Thus, it is not commercial
      activity or links per se that have become the target for criticism but the
      perceived influence of commercial enterprises on clinical decision-making or on
      messages conveyed by professional medical organizations. This document offers the
      perspective of the ESC on the current debate, and it recommends how to minimize
      bias in scientific communications and CME and how to ensure proper ethical
      standards and transparency in relations between the medical profession and
      industry.

PMID- 22383147
TI  - Fabrication of robust optical fibers by controlling film drainage of colloids in
      capillaries.

PMID- 22383148
TI  - Rapid screening of chemical warfare nerve agent metabolites in urine by
      atmospheric solids analysis probe-mass spectroscopy (ASAP-MS).
AB  - Exposures to organophosphorus nerve agents (OPNA) remain a threat to both
      civilian and military populations. Verification of exposures typically involves
      determinations of urinary metabolites or adducted proteins in blood. Urinary
      alkyl methylphosphonic acid metabolites resulting from hydrolysis of OPNAs
      provide a convenient marker for OPNA exposure. In a military setting, urine is a
      relatively easy sample to obtain, and a rapid turnaround for analyses for the
      identification of metabolites is critical for field commanders. Timely
      information on use and identity of OPNAs facilitates decisions regarding
      employment of personal protective equipment and additional strategies to mitigate
      additional exposure(s). Herein, we report the development of a rapid mass
      spectrometric (MS) method to identify OPNA metabolites directly from urine with
      no sample preparation. Synthetic urine spiked with multiple OPNA metabolites was
      analyzed using an atmospheric solids analysis probe (ASAP) attached to a high
      resolution mass spectrometer. The alkyl methylphosphonic acid metabolites
      resulting from hydrolysis of sarin, cyclosarin, soman, and Russian VX were
      clearly detectable down to a level of 1.0 ng/ml. The ability to rapidly detect
      OPNA metabolites in unprepared urine allows for the design of a field-deployable
      device that could afford field personnel the ability to rapidly screen
      individuals for specific OPNA exposure. In addition, this provides proof-of
      concept evidence that a fieldable ASAP-MS device could afford personnel the
      ability to rapidly detect OPNAs on skin, equipment, and other porous surfaces.
      Published 2012. This article is a US Government work and is in the public domain
      in the USA.

PMID- 22383149
TI  - Extensive metastasectomy for a single lesion with cardiac invasion.
AB  - Cardiac metastases are rare and considered a sign of end-stage oncologic disease.
      A lack of telltale clinical symptoms leads to late detection, thus usually
      limiting surgical options. Modern diagnostic tools such as fluorodeoxyglucose
      positron emission tomography, single-photon emission computed tomography, or
      cardiac magnetic resonance imaging could allow for timely detection and open up
      new therapeutic options. Highly selected oligometastatic patients may benefit
      from extensive surgical procedures including transmyocardial resection.

PMID- 22383150
TI  - The best of both worlds: staged hybrid approach to complex cardiac disease in a
      patient at high surgical risk.
AB  - For elderly patients with relevant comorbidities, combined cardiac surgery may be
      inadequate due to excessive surgical risk. Combining interventional valvular and
      surgical approaches may decrease surgical burden and operative risk. In the
      present case, we report a staged strategy of interventional mitral valve repair
      and secondary surgical aortic valve replacement and replacement of the ascending
      aorta in a patient at high risk for surgery. This hybrid approach allowed for
      substitution of one part of surgery by the relatively low-risk MitraClip
      procedure. For the future, increasing clinical importance of interventional valve
      therapies either for stand-alone or hybrid procedures can be anticipated. 

PMID- 22383151
TI  - Fluoroscopy-assisted thoracoscopic resection for small intrapulmonary lesions
      after preoperative computed tomography-guided localization using fragmented
      platinum microcoils.
AB  - BACKGROUND: Preoperative localization is frequently necessary to perform
      thoracoscopic resection of a small and/or deeply located intrapulmonary lesion.
      We developed a new method that uses a fragmented platinum microcoil, and
      retrospectively evaluated the efficacy of our technique. METHODS: Between January
      2006 and May 2010, self-made microcoils (Easimarker) were used to localize total
      32 lesions (21 solid nodules, and 11 ground glass opacities) in 30 patients.
      Computed tomography-guided localization was performed into, or just around the
      lesions. Localized lesions were resected using fluoroscopy-assisted thoracoscopic
      surgery (FATS), and the histopathologic diagnosis was confirmed. The accuracy and
      complications of the localization procedure, and operative results of FATS were
      observed. RESULTS: Mean size and depth of all lesions were 11.8 +/- 5.1 mm
      (range: 3 to 22) and 12.2 +/- 7.1 mm (range: 2 to 30). CT-guided localizations
      were successfully performed in all lesions. Four minimal pneumothorax and one
      parenchymal hematoma related with localization procedure occurred. There were
      three repeated procedures, which resulted from pleural rebounding of the
      microcoils. There were two microcoil detecting failures due to intrathoracic
      displacement during FATS. All 32 resected lesions were histopathologically
      diagnosed. CONCLUSION: CT-guided localization using the fragmented microcoil
      combined with FATS of small intrapulmonary lesions is a safe, effective, and a
      diagnostically accurate procedure.

PMID- 22383152
TI  - The role of residual tumor resection in the management of nonseminomatous germ
      cell cancer of testicular origin.
AB  - OBJECTIVE: To assess the outcome of patients with testicular nonseminomatous germ
      cell tumors (TNSGCT) undergoing intrathoracic residual tumor resection (RTR)
      after previous chemotherapy (CT) at a single institution. METHODS: The office
      records of all patients who underwent intrathoracic RTR for TNSGCT after CT at a
      single institution from January 2000 through December 2006 were reviewed.
      RESULTS: There were 124 consecutive patients (age 33.1 +/- 8.4 years) with
      residual masses who underwent 189 surgical procedures. Morbidity and mortality
      rates were 12.7 and 0.5%, respectively. Complete resections could be achieved in
      121 patients (97.6%). In the resected lung masses, necrosis was the predominant
      histology, (44.4 vs. 29% in mediastinal masses p = 0.018). Mature teratoma was
      the leading histology in the mediastinum (62.1 vs. 39.5% in lung masses, p =
      0.0006). Fifty-nine out of 124 patients (47.6%) required interventions at both
      lungs and had discordant histological results in 20.3% (12/59) of the cases. Mean
      survival was 86.6 +/- 2.6 months. The overall 5-year-survival and 10-year
      survival rates were 87 and 85%, respectively. Viable cancer, incomplete
      resections, age >= 34 years, and major pulmonary resections were associated with
      inferior survival in a univariate Cox proportional hazards model. In a
      multivariable Cox proportional hazards model, viable cancer, incomplete
      resections, and major pulmonary resections remained significant prognostic
      factors. CONCLUSIONS: In selected TNSGCT patients with residual masses, RTR can
      be performed safely after CT. RTR should be attempted at all sites because of
      possible discordant histological differentiation. Complete and parenchyma-sparing
      resections are associated with excellent long-term survival, which can be
      influenced by the surgeon.

PMID- 22383153
TI  - Outcomes following surgery for complicated tuberculosis: analysis of 108
      patients.
AB  - BACKGROUND: Both incidence and complications of pleuropulmonary tuberculosis (TB)
      have increased due to recent increase of immunocompromising conditions. The aim
      of this study was to assess surgical outcomes in patients suffering from
      complicated pleuropulmonary TB. METHODS: This study included 108 patients with
      pleuropulmonary TB who underwent surgery. Age, sex, surgical indications,
      operative techniques, complications, mortality, and morbidity were evaluated.
      RESULTS: Male-female ratio was 1:11 with mean age of 40 years; 72.2 and 27.8% of
      the patients underwent surgery due to parenchymal and pleural complications. In
      the parenchymal group, the most common indication was parenchymal destruction
      (27.7%) and the most common procedure was lobectomy (50.9%). Out of 20 sputum
      smear-positive patients, 15 had multidrug-resistant tuberculosis (MDR-TB) and 5
      had smear-positive open cavity. Overall 13 of the MDR-TB group and all smear
      positive open cavity group became sputum-negative after the surgery. There were
      13 patients with undiagnosed masses, among whom 3 patients had adenocarcinoma. In
      the pleural group, the most common surgical indication was empyema (13.8%) and
      the most common procedure was decortication and pleurectomy (13.8%). In the
      bronchopleural fistula group (6.4%), patients showed good results after surgery.
      There were 19.4% of patients who showed postoperative complications. The most
      common complication was residual space (5.5%). The main factors leading to major
      postoperative complications included positive preoperative sputum smear and
      history of immunocompromising condition. Mortality rate was 2.7%. CONCLUSION:
      Considering the favorable results achieved by surgery in patients with
      pleuropulmonary TB, this treatment can be recommended for this group of patients.

PMID- 22383154
TI  - Sternal dehiscence accompanied by protrusion of the left lung through the chest
      wall.
AB  - We report an almost complete protrusion of the lung through the anterior chest
      wall occurring as a complication following sternal dehiscence. Emergency
      treatment is mandatory since it has a high potential for incarceration,
      hemopneumothorax, respiratory failure, and infection. Twenty-eight days after
      coronary by-pass surgery, the left lung of a 66-year-old male patient almost
      completely protruded through the sternotomy incision in the chest wall; the lung
      tissue was successfully reduced and the sternotomy was closed. Recurrence was not
      observed within the 6-month follow-up period, his general condition was good. The
      clinical course of the patient was retrospectively reviewed, and this case was
      reported with a unique complication.

PMID- 22383155
TI  - Graft selection for the right coronary artery territory in off-pump coronary
      artery bypass.
AB  - BACKGROUND: The ideal bypass conduit in a right coronary artery (RCA) system
      remains controversial. METHODS: We analyzed 121 patients who underwent off-pump
      coronary artery bypass with internal thoracic arteries for the left coronary
      artery system and either in situ a right gastroepiploic artery (RGEA; n = 66) or
      a saphenous vein graft (SVG; n = 55) for the RCA system were enrolled. Follow-up
      coronary computed tomographic angiographic data were reviewed. RESULTS: The RGEA
      group showed higher graft patency at 5 years, especially in high grade stenosis
      (>= 80%; p = 0.009). In the SVG group, no difference was found between high grade
      stenosis and low grade stenosis. Freedom from adverse cardiac events at 5 years
      was higher in the RGEA group (p = 0.006). On multivariate analysis, low grade
      stenosis of RCA was predictive of graft failure (p = 0.029, hazard ratio = 10.9).
      CONCLUSIONS: In high grade stenosis of RCA, the RGEA group showed higher patency
      rate. The patency rate of SVG was not dependent on the degree of stenosis of RCA.

PMID- 22383156
TI  - Congenital diaphragmatic hernia: unusual presentation in an adult.
AB  - Congenital abnormalities account to no more than 3% among live births. Among
      those, less than 0.003% involve the diaphragm. Congenital diaphragmatic hernias
      are mostly diagnosed early in life, later diagnosis is rare, especially if the
      hernia is asymptomatic. Foreign body ingestion is primarily an issue in pediatric
      medicine, with very rare adults ingesting foreign bodies, these adults are
      usually mentally impaired. We present a 26-year-old mentally intact patient,
      presenting to us with foreign body ingestion, that on chest radiographs and
      computerized tomography, prove to be residing in his intestines. The intestines
      are herniating into the left chest. To our knowledge, no similar case has been
      reported and published.

PMID- 22383157
TI  - Genetic variation and structure of the endangered Lady Fern Athyrium
      viridescentipes based on ubiquitous genotyping.
AB  - To clarify the genetic status and provide effective information for the
      conservation of Athyrium viridescentipes, a critically endangered fern species
      with only 103 individuals remaining in the wild, we conducted ubiquitous
      genotyping to determine the genotypes of all remnant individuals of the target
      species. We analyzed the genetic variation of the 103 known individuals in four
      populations by using 13 microsatellite loci. The genotypes of single spores from
      a sporophytic individual were also determined in order to reveal the breeding
      system of this species. The level of allelic variation in A. viridescentipes was
      significantly lower than that of closely related Athyrium species. The genetic
      composition of the four populations was rather similar. Sixty-nine individuals
      (67%) possessed an identical pattern in the allele combinations at 13
      microsatellite loci. The mean pairwise F (ST) among four populations was 0.018.
      The segregated pattern of alleles, determined by single-spore genotyping,
      revealed that allelic recombination occurs through meiosis. The results indicate
      that this species contains a low level of genetic variation, has low population
      differentiation, and maintains populations by sexual reproduction. These findings
      could lead to more effective conservation programs, the selection of the most
      appropriate individuals for ex situ conservation efforts, and separate management
      of extant populations.

PMID- 22383159
TI  - Transcription factor 4 and myocyte enhancer factor 2C mutations are not common
      causes of Rett syndrome.
AB  - The systematic screening of Rett syndrome (RTT) patients for pathogenetic
      sequence variations has focused on three genes that have been associated with RTT
      or related clinical phenotypes, namely MECP2, CDKL5, and FOXG1. More recently, it
      has been suggested that phenotypes associated with TCF4 and MEF2C mutations may
      represent a form of RTT. Here we report on the screening of the TCF4 and MEF2C
      genes in a cohort of 81 classical, atypical, and incomplete atypical RTT patients
      harboring no known mutations in MECP2, CDKL5, and FOXG1 genes. No pathogenetic
      sequence variations were identified in the MEF2C gene in our cohort. However, a
      frameshift mutation in TCF4 was identified in a patient with a clinical diagnosis
      of "variant" RTT, in whom the clinical evolution later raised the possibility of
      Pitt-Hopkins syndrome. Although our results suggest that these genes are not
      commonly associated with RTT, we note the clinical similarity between RTT and
      Pitt-Hopkins syndrome, and suggest that RTT patients with no mutation identified
      in MECP2 be considered for molecular screening of the TCF4 gene.

PMID- 22383160
TI  - Differential responses in sympatric tree species exposed to waterlogging.
AB  - Climate change is projected to have a significant ecological impact on natural
      ecosystems, most notably through direct and indirect modifications of local
      precipitation regimes. In addition, anthropic activities such as the removal of
      vegetation, soil proofing due to building, the absence of storm drains and crop
      over-irrigation will all increase the occurrence of flooding. As a result, forest
      species, and more specifically trees, will increasingly be exposed to soil
      waterlogging. It is now well established that such flooding events can lead to
      changes in forest distribution and composition. For such reasons, it is becoming
      increasingly important to study forest ecosystems and more particularly the
      adaptive potential of tree species to better understand the ecological plasticity
      of forest communities to environmental modifications.

PMID- 22383161
TI  - Message from the editor-in-chief.

PMID- 22383162
TI  - Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2
      expression in biliary epithelium of patients with primary biliary cirrhosis.
AB  - Cl(-) /HCO3- anion exchanger 2 (AE2) participates in intracellular pH homeostasis
      and secretin-stimulated biliary bicarbonate secretion. AE2/SLC4A2 gene expression
      is reduced in liver and blood mononuclear cells from patients with primary
      biliary cirrhosis (PBC). Our previous findings of hepatic and immunological
      features mimicking PBC in Ae2-deficient mice strongly suggest that decreased AE2
      expression might be involved in the pathogenesis of PBC. Here, we tested the
      potential role of microRNA 506 (miR-506) - predicted as candidate to target AE2
      mRNA - for the decreased expression of AE2 in PBC. Real-time quantitative
      polymerase chain reaction showed that miR-506 expression is increased in PBC
      livers versus normal liver specimens. In situ hybridization in liver sections
      confirmed that miR-506 is up-regulated in the intrahepatic bile ducts of PBC
      livers, compared with normal and primary sclerosing cholangitis livers. Precursor
      mediated overexpression of miR-506 in SV40-immortalized normal human
      cholangiocytes (H69 cells) led to decreased AE2 protein expression and activity,
      as indicated by immunoblotting and microfluorimetry, respectively. Moreover, miR
      506 overexpression in three-dimensional (3D)-cultured H69 cholangiocytes blocked
      the secretin-stimulated expansion of cystic structures developed under the 3D
      conditions. Luciferase assays and site-directed mutagenesis demonstrated that miR
      506 specifically may bind the 3'untranslated region (3'UTR) of AE2 messenger RNA
      (mRNA) and prevent protein translation. Finally, cultured PBC cholangiocytes
      showed decreased AE2 activity, together with miR-506 overexpression, compared to
      normal human cholangiocytes, and transfection of PBC cholangiocytes with anti-miR
      506 was able to improve their AE2 activity. CONCLUSION: miR-506 is up-regulated
      in cholangiocytes from PBC patients, binds the 3'UTR region of AE2 mRNA, and
      prevents protein translation, leading to diminished AE2 activity and impaired
      biliary secretory functions. In view of the putative pathogenic role of decreased
      AE2 in PBC, miR-506 may constitute a potential therapeutic target for this
      disease.

PMID- 22383163
TI  - Enlarging arachnoid cyst: a false alarm for infants.
AB  - PURPOSE: The natural history of change in size of arachnoid cysts (ACs) is an
      unsettled issue. This leads to confusion in deciding treatment strategies of
      incidental, asymptomatic AC in children, since the risks and complications of
      surgery are not negligible. The aim of the present study was to elucidate the
      clinical significance of change in size of AC in young children. METHODS: From
      2000 to 2008, 86 patients younger than 5 years with AC documented on brain
      imaging were included. They were divided into four different age groups (group I:
      0-0.5 year, group II: 0.5-1 year, group III: 1-3 years, group IV: 3-5 years). The
      temporal changes in size of the AC on consecutive ultrasonography, computed
      tomography (CT), or magnetic resonance imaging (MRI) of each patient were
      measured and plotted as individual graphs. Natural progression of AC size was
      assessed by evaluation of the pattern of each graph. RESULTS: Seventeen patients
      showed enlargement of AC during follow-up; 14 patients were younger than 1 year.
      None of the patients in group IV showed enlargement during follow-up. Overall, 11
      of the 17 patients with demonstrated AC enlargement were not operated on. In six
      patients, AC enlargement ceased, and spontaneous regression was observed in three
      patients. The remaining two untreated patients had shown asymptomatic increase in
      size at last follow-up. Statistical analysis revealed age at diagnosis to be the
      only significant factor affecting cyst enlargement. CONCLUSION: Asymptomatic
      enlargement of AC in infants may not be an indication for surgical intervention.
      Close follow-up is a viable option for such children.

PMID- 22383164
TI  - Severely impaired wound healing in a Fontan patient after neurosurgery: a novel
      topic in univentricular heart physiology?

PMID- 22383165
TI  - The 5' -> 3' exoribonuclease XRN1/Pacman and its functions in cellular processes
      and development.
AB  - XRN1 is a 5' -> 3' processive exoribonuclease that degrades mRNAs after they have
      been decapped. It is highly conserved in all eukaryotes, including homologs in
      Drosophila melanogaster (Pacman), Caenorhabditis elegans (XRN1), and
      Saccharomyces cerevisiae (Xrn1p). As well as being a key enzyme in RNA turnover,
      XRN1 is involved in nonsense-mediated mRNA decay and degradation of mRNAs after
      they have been targeted by small interfering RNAs or microRNAs. The crystal
      structure of XRN1 can explain its processivity and also the selectivity of the
      enzyme for 5' monophosphorylated RNA. In eukaryotic cells, XRN1 is often found in
      particles known as processing bodies (P bodies) together with other proteins
      involved in the 5' -> 3' degradation pathway, such as DCP2 and the helicase DHH1
      (Me31B). Although XRN1 shows little specificity to particular 5'
      monophosphorylated RNAs in vitro, mutations in XRN1 in vivo have specific
      phenotypes suggesting that it specifically degrades a subset of RNAs. In
      Drosophila, mutations in the gene encoding the XRN1 homolog pacman result in
      defects in wound healing, epithelial closure and stem cell renewal in testes. We
      propose a model where specific mRNAs are targeted to XRN1 via specific binding of
      miRNAs and/or RNA-binding proteins to instability elements within the RNA. These
      guide the RNA to the 5' core degradation apparatus for controlled degradation.

PMID- 22383166
TI  - From preclinical to human--prediction of oral absorption and drug-drug
      interaction potential using physiologically based pharmacokinetic (PBPK) modeling
      approach in an industrial setting: a workflow by using case example.
AB  - PURPOSE: A case example is presented in which the physiologically based modeling
      approach has been used to model the absorption of a lipophilic BCS Class II
      compound predominantly metabolized by CYP3A4, and to assess the interplay of
      absorption related parameters with the drug-drug interaction (DDI) potential.
      METHODS: The PBPK model was built in the rat using Gastroplus(r) to study the
      absorption characteristics of the compound. Subsequently relevant model
      parameters were used to predict the non-linear human PK observed during first-in
      human study after optimizing the absorption model for colonic absorption, bile
      micelle solubilization and unbound fraction in gut enterocytes (fu(gut)) using
      SIMCYP(r) simulator. The model fitted absorption parameters were then used to
      assess the drug-drug interaction (DDI) potential of the test compound when
      administered along with multiple doses of a potent CYP 3A4 inhibitor,
      ketoconazole. The impact of fu(gut) in the extent of DDI was assessed using
      parameter sensitivity analysis. RESULTS AND CONCLUSIONS: After optimizing the
      preclinical model and taking into consideration bile micelle solubilization and
      colonic absorption, the non-linear pharmacokinetics of the test compound was
      satisfactorily predicted in man. Sensitivity analysis performed with the
      absorption parameter fu(gut) indicated that it could be an important parameter in
      predicting oral absorption. In addition, DDI simulations using SIMCYP(r) suggest
      that C(max) and AUC ratios may also be sensitive to the fu(gut) input in the
      model. Since fu(gut) cannot be measured experimentally, sensitivity analysis may
      help in assessing the importance of fu(gut) in human PK and DDI prediction using
      SIMCYP(r).

PMID- 22383167
TI  - Quantitative neurodegenerative pathology does not explain the degree of
      hippocampal atrophy on MRI in degenerative dementia.
AB  - OBJECTIVE: The purpose of this study was to investigate the neuropathological
      substrates underlying in vivo hippocampal atrophy on magnetic resonance imaging
      (MRI) in autopsy confirmed neurodegenerative dementia cases. METHODS: Thirty-one
      neuropathologically verified cases (23 with Lewy body dementia (LBD) and eight
      with Alzheimer's disease (AD)) were included who had undergone an MRI scan close
      to death (mean 1.5 years). Manual volumetric measurements were undertaken for the
      hippocampus, entorhinal cortex and amygdala on MRI, along with quantitative
      neuropathological analysis of plaque, tangle and Lewy body pathology in the same
      regions. The relationship between neuropathology and MRI volumes was assessed
      using correlations and linear regression. RESULTS: Hippocampal and amygdala
      volumes were significantly smaller in cases with AD than with LBD, but there was
      no difference in entorhinal cortex volume. Analysing all cases together, a
      significant positive correlation was observed between normalised hippocampal
      volume and percent area of Lewy bodies in the hippocampus (r=0.449, p=0.017) but
      not with tangles (r=0.059, p=0.766) or plaques (r=-0.361, p=0.119). There were no
      other significant correlations between regional MRI volume and measures of
      neuropathology. Regression analysis showed that overall diagnosis of AD rather
      than burden of individual pathological changes was the most significant predictor
      of hippocampal volume loss in autopsy confirmed cases. CONCLUSION: Our results
      suggest that (i) hippocampal and amygdala but not entorhinal cortex, volumes
      differ between AD and LBD and (ii) factors other than current markers of
      neurodegenerative pathological change are responsible for atrophy of medial
      temporal lobe structures in AD and LBD.

PMID- 22383168
TI  - Digital infrared thermal imaging following anterior cruciate ligament
      reconstruction.
AB  - This case describes the selective use of digital infrared thermal imaging for a
      48-year-old woman who was being treated by a physical therapist following left
      anterior cruciate ligament (ACL) reconstruction with a semitendinosus autograft.

PMID- 22383169
TI  - The miR-17-92 cluster and its target THBS1 are differentially expressed in
      angiosarcomas dependent on MYC amplification.
AB  - Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors
      that may occur spontaneously as primary tumors or secondarily after radiation
      therapy or in the context of chronic lymphedema. Most secondary ASs have been
      associated with MYC oncogene amplification, whereas the role of MYC abnormalities
      in primary AS is not well defined. Twenty-two primary and secondary ASs were
      analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing
      of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in
      situ hybridization, MYC amplification was identified in three out of six primary
      tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new
      potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92
      cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification
      and the control group (other vascular tumors, nonvascular sarcomas). Moreover,
      MYC-amplified ASs were associated with a significantly lower expression of
      thrombospondin-1 (THBS1) than AS without MYC amplification or controls.
      Altogether, our study implicates MYC amplification not only in the pathogenesis
      of secondary AS but also in a subset of primary AS. Thus, MYC amplification may
      play a crucial role in the angiogenic phenotype of AS through upregulation of the
      miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous
      inhibitor of angiogenesis.

PMID- 22383170
TI  - Cervical hematomyelia after traditional Chinese massage: a case report.
AB  - Hematomyelia is rare, and usually related to major trauma. Non-traumatic causes
      are much rarer and include underlying vascular malformations and cord tumors. We
      present the case of a previously well 44-year-old woman who developed severe
      acute neck pain and right-sided motor deficit after a session of traditional
      Chinese massage that entailed minimal neck manipulation. Emergent MRI confirmed
      hematomyelia of the right cervical hemicord, notably without associated bony or
      ligamentous injury. Follow-up spinal angiography and MRIs revealed no underlying
      vascular malformation or tumor. We highlight this case as there has been no
      reported case of hematomyelia occurring after mild trauma, although two cases of
      idiopathic hematomyelia have been reported. Though exceedingly rare, hematomyelia
      should be considered in the list of differential diagnoses in any case of neck
      pain and motor deficit after seemingly trivial injury.

PMID- 22383172
TI  - Enlarged parietal foramina: two rediscovered cases.

PMID- 22383171
TI  - The complex spectrum of forensic issues arising from obesity.
AB  - The increasing numbers of obese and morbidly obese individuals in the community
      are having a direct effect on forensic facilities. In addition to having to
      install more robust equipment for handling large bodies, the quality of autopsy
      examinations may be reduced by the physical difficulties that arise in trying to
      position bodies correctly so that normal examinations can proceed. Accelerated
      putrefaction is often an added complication. Metabolic disturbances resulting
      from obesity increase susceptibility to a range of conditions that are associated
      with sudden and unexpected death, and surgery may have increased complications.
      The rates of a number of different malignancies, including lymphoma, leukemia,
      melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon,
      gallbladder, thyroid, prostate, breast and endometrium, are increased. In
      addition, obese individuals have higher rates of diabetes mellitus, and sepsis.
      The unexpected collapse of an obese individual should raise the possibility of a
      wide range of conditions, many of which may be more difficult to demonstrate at
      autopsy than in an individual with a normal body mass index. Although sudden
      cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart
      disease may be the most probable diagnosis in an unexpected collapse, the range
      of possible underlying conditions is extensive and often only determinable after
      full postmortem examination.

PMID- 22383173
TI  - Fatal intraabdominal bleeding from ectopic varices: report of two autopsy cases.

PMID- 22383174
TI  - Hypothesis: Estrogen related thrombosis explains the pathogenesis and
      epidemiology of gastroschisis.
AB  - A three-part hypothesis is proposed to explain the unusual epidemiology of
      gastroschisis, a congenital abnormality of the abdominal wall, which has a rising
      frequency, a higher rate in first and young mothers in whites but not blacks, and
      a unique negative correlation with obesity. The hypothesis involves: (1) An early
      estrogenic thrombophilia, (2) racial differences in thrombosis, and (3)
      thrombotic by-products interfering with early developmental signaling. For the
      first: (1) An estrogenic thrombophilia is a known effect. (2) A mouse model links
      excess estrogen to thromboses affecting the fetus. (3) Young and first mothers
      have higher first trimester estrogen levels. (4) A negative correlation between
      body mass index and pregnancy estradiol accounts for the weight relationship. (5)
      Maternal alcohol raises estrogen levels in premenopausal women. (6) A link with
      atrazine, an estrogenic endocrine disruptor, has been found, and rising
      frequencies of gastroschisis make this and other such chemicals a particular
      concern if estrogen is indeed involved. For the second: Blacks have a different
      thrombophilic gene background and less of a thrombotic response to estrogen than
      whites, explaining racial differences. For the third: Protein palmitoylation
      affects cell signaling in development, and lipid rafts, a major aspect of
      thromboses, facilitate this process. Such thrombotic byproducts could be the
      source of palmitic acid rich amniotic vacuoles with gastroschisis. Similar
      vacuoles can occur with limb-body wall defects, another early developmental
      anomaly associated with decreased maternal age that may have a similar
      pathogenesis. Later thrombotic related anomalies with a similar epidemiology seem
      to primarily involve vascular disruptions, but localized signaling anomalies may
      also occur.

PMID- 22383175
TI  - Peri-implantitis: from diagnosis to therapeutics.
AB  - Peri-implantitis is an infection of the tissue around an implant, resulting in
      the loss of supporting bone. Risk factors for peri-implantitis consist of a
      history of periodontitis, dental plaque, poor oral hygiene, smoking, alcohol
      consumption and diabetes. A clinical diagnosis indicates inflammatory signs
      including bleeding on probing with or without suppuration and a peri-implant
      pocket depth >=5 mm. A radiograph shows images of marginal bone loss >=2 mm. A
      differential diagnosis of peri-implant mucositis, occlusal overload, retrograde
      peri-implantitis and inflammatory implant periapical lesions suggests the
      appropriate treatment in each case. The non-surgical treatment of peri
      implantitis, including a mechanical treatment alone or combined with antiseptics
      or antibiotics can improve clinical parameters in the short term but residual
      defects may still persist. Surgical treatment such as guided bone regeneration
      results in a gain of clinical attachment level and bone reconstruction in the
      long term. The limited effect of laser-assisted therapy needs to be further
      evaluated. The concept of prevention based on early detection and regular
      maintenance plays a principal role in reducing the occurrence of peri
      implantitis.

PMID- 22383176
TI  - Photosynthetic accumulation of carbon storage compounds under CO2 enrichment by
      the thermophilic cyanobacterium Thermosynechococcus elongatus.
AB  - The growth characteristics of Thermosynechococcus elongatus on elevated CO2 were
      studied in a photobioreactor. Cultures were able to grow on up to 20% CO2. The
      maximum productivity and CO2 fixation rates were 0.09 +/- 0.01 and 0.17 +/- 0.01
      mg ml-1 day-1, respectively, for cultures grown on 20% CO2. Three major carbon
      pools--lipids, polyhydroxybutyrates (PHBs), and glycogen--were measured. These
      carbon stores accounted for 50% of the total biomass carbon in cultures grown on
      atmospheric CO2 (no supplemental CO2), but only accounted for 30% of the total
      biomass carbon in cultures grown on 5-20% CO2. Lipid content was approximately
      20% (w/w) under all experimental conditions, while PHB content reached 14.5%
      (w/w) in cultures grown on atmospheric CO2 and decreased to approximately 2.0%
      (w/w) at 5-20% CO2. Glycogen levels did not vary significantly and remained about
      1.4% (w/w) under all test conditions. The maximum amount of CO2 sequestered over
      the course of the nine-day chemostat experiment was 1.15 g l-1 in cultures grown
      on 20% CO2.

PMID- 22383177
TI  - Integrated organic-aqueous biocatalysis and product recovery for quinaldine
      hydroxylation catalyzed by living recombinant Pseudomonas putida.
AB  - In an earlier study, biocatalytic carbon oxyfunctionalization with water serving
      as oxygen donor, e.g., the bioconversion of quinaldine to 4-hydroxyquinaldine,
      was successfully achieved using resting cells of recombinant Pseudomonas putida,
      containing the molybdenum-enzyme quinaldine 4-oxidase, in a two-liquid phase
      (2LP) system (Utkur et al. J Ind Microbiol Biotechnol 38:1067-1077, 2011). In the
      study reported here, key parameters determining process performance were
      investigated and an efficient and easy method for product recovery was
      established. The performance of the whole-cell biocatalyst was shown not to be
      limited by the availability of the inducer benzoate (also serving as growth
      substrate) during the growth of recombinant P. putida cells. Furthermore,
      catalyst performance during 2LP biotransformations was not limited by the
      availability of glucose, the energy source to maintain metabolic activity in
      resting cells, and molecular oxygen, a possible final electron acceptor during
      quinaldine oxidation. The product and the organic solvent (1-dodecanol) were
      identified as the most critical factors affecting biocatalyst performance, to a
      large extent on the enzyme level (inhibition), whereas substrate effects were
      negligible. However, none of the 13 alternative solvents tested surpassed 1
      dodecanol in terms of toxicity, substrate/product solubility, and partitioning.
      The use of supercritical carbon dioxide for phase separation and an easy and
      efficient liquid-liquid extraction step enabled 4-hydroxyquinaldine to be
      isolated at a purity of >99.9% with recoveries of 57 and 84%, respectively. This
      study constitutes the first proof of concept on an integrated process for the
      oxyfunctionalization of toxic substrates with a water-incorporating hydroxylase.

PMID- 22383179
TI  - Prophylactic and therapeutic implications of toll-like receptor ligands.
AB  - The evolutionary conserved Toll-like receptors (TLRs) are the first identified
      and best characterized pattern recognition receptors (PRRs) which discriminate
      self from nonself, providing an early and effective immune response against
      invading pathogens. The ever expanding knowledge of TLR signaling network make it
      one of the most promising therapeutic strategies to modulate the immune response
      in various human diseases. Immune modulating strategies based on TLR-specific
      agonists elicit a potent immune response to adjuvant vaccine immunotherapy,
      cancers, allergic diseases, and chronic viral infections while minimizing the
      risk of uncontrolled provocation of systemic inflammatory response. Moreover, the
      contribution of TLR signaling in the pathogenesis of chronic noninfectious
      inflammatory and autoimmune diseases provides the rationale for the development
      and clinical implementation of TLR-specific antagonists. At present, a few TLR
      specific agonists have been approved for both prophylactic and therapeutic
      applications, while the ongoing preclinical and clinical studies show promising
      results on various novel therapeutic molecules as an adjunctive to conventional
      pharmacotherapy or stand-alone therapeutic strategy.

PMID- 22383180
TI  - Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human
      cancers.
AB  - Specific and sensitive non-invasive biomarkers for the detection of human
      epithelial malignancies are urgently required to reduce the worldwide morbidity
      and mortality caused by cancer. MicroRNAs (miRNAs) are 19-24 nt noncoding RNAs
      that are frequently dysregulated in cancer and have shown great promise as tissue
      based markers for cancer classification. Once thought to be unstable RNA
      molecules, miRNAs are now shown to be stably expressed in serum, plasma, urine,
      saliva, and other body fluids. Moreover, the unique expression patterns of these
      circulating miRNAs are correlated with certain human diseases, including various
      types of cancer. Therefore, tumor-derived miRNAs in serum or plasma are emerging
      as novel blood-based fingerprints for the detection of human cancers, especially
      at an early stage. This review presented newly uncovered cellular and molecular
      mechanisms of the sources and stability of circulating miRNAs, revealing their
      great potential as a class of highly specific and sensitive biomarkers for tumor
      classification and prognostication. Meanwhile, this review also addressed certain
      critical issues that hinder the wide application of this new approach. Some
      potential challenges for the transition of circulating miRNAs from a research
      setting to a clinical application were also highlighted, with a future
      perspective of the incorporation of circulating miRNAs in the field of clinical
      oncology, especially their great potential from diagnostic to prognostic and
      predictive applications.

PMID- 22383181
TI  - Safe and well-tolerated treatment with ivabradine in systemic sclerosis affected
      by pulmonary hypertension.

PMID- 22383182
TI  - Experimental determination of thermodynamic equilibrium in biocatalytic
      transamination.
AB  - The equilibrium constant is a critical parameter for making rational design
      choices in biocatalytic transamination for the synthesis of chiral amines.
      However, very few reports are available in the scientific literature determining
      the equilibrium constant (K) for the transamination of ketones. Various methods
      for determining (or estimating) equilibrium have previously been suggested, both
      experimental as well as computational (based on group contribution methods).
      However, none of these were found suitable for determining the equilibrium
      constant for the transamination of ketones. Therefore, in this communication we
      suggest a simple experimental methodology which we hope will stimulate more
      accurate determination of thermodynamic equilibria when reporting the results of
      transaminase-catalyzed reactions in order to increase understanding of the
      relationship between substrate and product molecular structure on reaction
      thermodynamics.

PMID- 22383183
TI  - Opposite roles of FOXA1 and NKX2-1 in lung cancer progression.
AB  - Gene copy number profiles of primary lung tumors were screened for high-level
      amplifications. We detected 22 high-level amplifications in various loci,
      including 14q13. This locus is known to harbor the adenocarcinoma (AC) lineage
      specific target gene NKX2-1, which is not expressed in squamous cell carcinoma
      (SCC). As the 14q amplification was also found in SCC, we investigated whether or
      not FOXA1 might be the corresponding target gene for SCC. Focusing on these two
      target genes, we assessed gene amplifications and protein expression of NKX2-1
      and FOXA1 in primary lung tumors (n = 554) and brain metastases (n = 68). Primary
      AC (n = 194) showed positive protein expression of NKX2-1 in 58.2% of the samples
      compared with 4.2% of primary SCC samples (n = 212). Positive staining for FOXA1
      was seen in 34.7% of the SCC samples, which was comparable with 39.6% in the AC
      samples. For brain metastases, FOXA1 expression was slightly higher in the SCC
      samples (55.6%) compared with the non-matched primary SCC tumor samples (43.4%),
      whereas NKX2-1 expression was comparable in both primary tumors and brain
      metastases. Positive FOXA1 and NKX2-1 expression was associated with a gain or
      amplification in 34.6% and 28.6% of cases, respectively. The expression of NKX2-1
      was associated with early stage and grade among the AC cases. In contrast, FOXA1
      expression in SCC was associated with distant metastases as well as an
      unfavorable survival rate (P = 0.039). These results suggest that both FOXA1 and
      NKX2-1 may act as lineage-specific target genes within the 14q amplicon with
      opposite functions in lung cancer.

PMID- 22383185
TI  - Editorial: Michael Shuler's legacy in biochemical engineering.

PMID- 22383188
TI  - The original biochemical engineer: an interview with Michael Shuler of Cornell
      University. Interviewed by Judy Peng.

PMID- 22383189
TI  - Meeting report: Functional genomics and proteomics - applications, molecular
      diagnostics & next generation sequencing.

PMID- 22383190
TI  - A ribosomal surprise.

PMID- 22383191
TI  - Model-guided strain improvement: simultaneous hydrolysis and co-fermentation of
      cellulosic sugars.

PMID- 22383195
TI  - Diabetes mellitus and oral health care: time for the next step.

PMID- 22383196
TI  - Sealants and EBD.

PMID- 22383197
TI  - More about sealants.

PMID- 22383199
TI  - Using a mouthpiece.

PMID- 22383201
TI  - More about mouthpieces.

PMID- 22383203
TI  - Ten-year outcome of three-unit fixed dental prostheses made from monolithic
      lithium disilicate ceramic.
AB  - BACKGROUND: The authors conducted a prospective study to evaluate the long-term
      outcome of crown-retained fixed dental prostheses (FDPs) made from monolithic
      lithium disilicate ceramic (IPS e.max Press, Ivoclar Vivadent, Schaan,
      Liechtenstein). METHODS: Faculty dentists at the Department of Prosthodontics,
      Propaedeutics and Dental Materials, School of Dentistry, Christian-Albrechts
      University at Kiel, Germany, placed 36 three-unit FDPs in 28 patients to replace
      six anterior and 30 posterior teeth. The proximal connector size (height and
      width) was 4 * 3 millimeters for anterior FDPs and 4 * 4 mm for posterior FDPs.
      FDPs were cemented either conventionally with glass ionomer cement (n = 19) or
      adhesively with resin-based composite (n = 17). Patients made annual recall
      visits. RESULTS: The mean (standard deviation) observation period was 121 (12.8)
      months. FDPs' survival rate (survival being defined as remaining in place either
      with or without complications) was 100 percent after five years and 87.9 percent
      after 10 years, and their success rate (success being defined as remaining
      unchanged and free of complications) was 91.1 percent after five years and 69.8
      percent after 10 years. The cementation method did not affect the outcome.
      CONCLUSION: Three-unit FDPs made from monolithic lithium disilicate ceramic
      showed five- and 10-year survival and success rates that were similar to those of
      conventional metal-ceramic FDPs. CLINICAL IMPLICATIONS: If the manufacturer's
      recommendations are followed, three-unit FDPs made from monolithic lithium
      disilicate ceramic may be a safe alternative to metal-ceramic FDPs regardless of
      the cementation method used.

PMID- 22383204
TI  - Evidence supporting the use of cone-beam computed tomography in orthodontics.
AB  - BACKGROUND: The authors conducted a systematic review of cone-beam computed
      tomography (CBCT) applications in orthodontics and evaluated the level of
      evidence to determine whether the use of CBCT is justified in orthodontics. TYPES
      OF STUDIES REVIEWED: The authors identified articles by searching the Cochrane
      Library, PubMed, MEDLINE, Embase, Scopus and Cumulative Index to Nursing and
      Allied Health Literature databases. They searched the articles' reference lists
      manually for additional articles and had no language limitations. They did not
      search the gray literature. Inclusion criteria were CBCT use in orthodontics and
      that the participants be human. The lowest level of evidence accepted for
      inclusion was a case series with five or more participants. The authors evaluated
      the studies' methodological quality according to 13 criteria related to study
      design, measurements and statistical analysis. RESULTS: The authors identified
      550 articles, and 50 met the inclusion criteria. Study topics included temporary
      anchorage devices, cephalometry, combined orthodontic and surgical treatment,
      airway measurements, root resorption and tooth impactions, and cleft lip and
      palate. The methodological quality averaged 53 percent (range, 15-77 percent) of
      the maximum score. CLINICAL IMPLICATIONS: The authors found no high-quality
      evidence regarding the benefits of CBCT use in orthodontics. Limited evidence
      shows that CBCT offers better diagnostic potential, leads to better treatment
      planning or results in better treatment outcome than do conventional imaging
      modalities. Only the results of studies on airway diagnostics provided sound
      scientific data suggesting that CBCT use has added value. The additional
      radiation exposure should be weighed against possible benefits of CBCT, which
      have not been supported in the literature. In future studies, investigators
      should evaluate the effects of CBCT on treatment procedures, progression and
      outcome quantitatively.

PMID- 22383205
TI  - Gingival lesions in a 21-year-old man.

PMID- 22383206
TI  - Using an n-of-1 trial to assist in clinical decision making for patients with
      orofacial pain.

PMID- 22383207
TI  - Random blood glucose testing in dental practice: a community-based feasibility
      study from The Dental Practice-Based Research Network.
AB  - BACKGROUND: The prevalence of diabetes mellitus (DM) has been increasing.
      Instances of patients' not having received a diagnosis have been reported widely,
      as have instances of poor control of DM or prediabetes among patient's who have
      the disease. These facts indicate that blood glucose screening is needed.
      METHODS: As part of The Dental Practice-Based Research Network, the authors
      conducted a study in community dental practices to test the feasibility of
      screening patients for abnormal random blood glucose levels by means of
      glucometers and finger-stick testing. Practitioners and staff members were
      trained to use a glucometer, and they then screened consecutive patients older
      than 19 years at each practice until 15 patients qualified for the study and
      provided consent. Perceived barriers to and benefits of blood glucose testing
      (BGT) were reported by patients and dental office personnel on questionnaires.
      RESULTS: Twenty-eight practices screened 498 patients. A majority of the
      respondents from the 67 participating dental offices considered BGT useful and
      worth routine implementation. They did not consider duration of BGT or its cost
      to be significant barriers. Among patients, more than 80 percent thought BGT in
      dental practice was a good idea and found it easy to withstand; 62 percent were
      more likely to recommend their dentists to others if BGT was offered. CONCLUSION:
      BGT was well received by patients and practitioners. These results support the
      feasibility of implementation of BGT in community dental practices. CLINICAL
      IMPLICATIONS: Improved diagnosis and control of DM may be achieved through
      implementation of BGT in community dental practices.

PMID- 22383208
TI  - Effectiveness of two disinfectant solutions and microwave irradiation in
      disinfecting complete dentures contaminated with methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) biofilm on
      dentures can be aspirated, thus causing infections such as aspiration pneumonia.
      The authors evaluated the efficacy of two disinfectant solutions and microwave
      irradiation in disinfecting complete dentures contaminated with MRSA. METHODS:
      The authors contaminated 36 simulated complete dentures with MRSA and divided
      them into four equal groups: a positive control group consisting of dentures that
      were not disinfected; a group that soaked in 1 percent sodium hypochlorite for 10
      minutes; a group that soaked in 2 percent chlorhexidine gluconate for 10 minutes;
      and a group that underwent microwave irradiation at 650 watts for three minutes.
      The authors quantified colony counts and evaluated the long-term effectiveness of
      disinfection. RESULTS: All dentures from the control group showed substantial
      microbial growth on the plates (6.24 log(10) colony-forming units per
      milliliter). The authors observed no evidence of microbial growth on plates of
      any disinfected dentures. After seven days' incubation, the authors observed
      broth turbidity in all beakers containing the dentures disinfected with 1 percent
      sodium hypochlorite. CONCLUSIONS: Soaking in chlorhexidine gluconate solution and
      microwave irradiation resulted in complete disinfection of all dentures
      contaminated with MRSA in both the short and the long term. Soaking in sodium
      hypochlorite solution was effective only as a short-term disinfectant. CLINICAL
      IMPLICATIONS: Microwave irradiation and 2 percent chlorhexidine gluconate may
      have a disinfective application in dental offices and institutions in which
      denture wearers are treated, thus improving the longevity and quality of life of
      patients and reducing the burden of disease caused by MRSA.

PMID- 22383209
TI  - Quantitative analysis of tooth surface loss associated with gastroesophageal
      reflux disease: a longitudinal clinical study.
AB  - BACKGROUND: Acid regurgitation resulting from gastroesophageal reflux disease
      (GERD) causes dissolution of tooth structure. The authors conducted a
      longitudinal clinical study to measure tooth surface loss associated with GERD.
      METHODS: The authors made replicas of dental impressions obtained from 12
      participants with GERD and six control participants at baseline and six months.
      Using an optical scanner, they digitized the tooth surfaces of these replicas.
      They then analyzed the volume of tooth surface loss and characterized it as
      noncontact erosion or erosion/attrition. RESULTS: Mean (standard deviation)
      volume loss per tooth in participants with GERD (0.18 [0.12] cubic millimeter)
      was significantly higher than that in control participants (0.06 [0.03] mm(3); t
      test; P < .013). Nine participants with GERD exhibited tooth surface loss with
      characteristics of erosion (noncontact erosion in three participants,
      erosion/attrition in eight participants). CONCLUSIONS: Tooth surface loss in
      participants with GERD was significantly greater than that in control
      participants. The pattern of surface loss was characteristic of erosion in
      noncontact areas and around contact areas. CLINICAL IMPLICATIONS: Anterior and
      posterior teeth of participants with GERD were affected by erosive tooth wear. In
      addition, the amount of erosive tooth wear on occlusal surfaces was twice as high
      when there was evidence of attrition.

PMID- 22383210
TI  - For mandibular overdentures, marginal bone loss may not be affected by implant
      design or attachment type.

PMID- 22383211
TI  - Dental insurance--yes or no?

PMID- 22383213
TI  - For the dental patient. Keep sports safe--wear a mouthguard.

PMID- 22383214
TI  - Falling through the cracks: gaps in depression treatment among older Mexican
      origin and white men.
AB  - OBJECTIVES: This study aims (i) to compare depression frequency and self-reported
      depression treatment in Mexican-origin and white men; (ii) to examine ethnic
      differences in self-reported prior depression diagnosis and types of treatment;
      and (iii) to determine whether Mexican-origin men (both English and Spanish
      language preferring) are less likely than white men to report receiving
      depression treatment after controlling for potential confounders. METHODS: This
      is a cross-sectional, observational study of Mexican-origin and white men (60
      years old and over) presenting for primary care visits at six outpatient clinics
      in California's Central Valley. Clinical depression was assessed with the
      Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV), module for past-year major depression and
      questions for chronic depression. Past year, self-reported prior depression
      diagnosis and treatment (i.e., medication, psychotherapy, mental health referral)
      were assessed through a structured questionnaire. RESULTS: The frequency of past
      year clinical depression was similar for both ethnic groups, yet Mexican-origin
      men were significantly less likely than whites to report receiving a prior
      diagnosis of depression or prior depression treatment. Compared with whites, the
      odds of untreated depression in Mexican-origin men was 4.35 (95% CI 1.35-14.08)
      for those interviewed in English and 10.40 (95% CI 2.11-51.25) for those
      interviewed in Spanish. For both ethnic groups, the majority (i.e., approximately
      two-thirds) of men receiving depression treatment also met criteria for past-year
      clinical depression. CONCLUSIONS: Mexican-origin older men in primary care suffer
      from significant gaps in depression care (i.e., diagnosis and treatment) compared
      with whites. Delivering effective depression treatment (i.e., so that depression
      remits) remains elusive for both ethnic groups.

PMID- 22383215
TI  - Laparoscopic transabdominal preperitoneal hernioplasty for reduction en masse of
      an incarcerated inguinal hernia: a case report.
AB  - INTRODUCTION: Reduction en masse is a rare complication of an incarcerated
      inguinal hernia. Its occurrence should be suspected when intestinal obstruction
      persists despite a seemingly successful manual reduction or hernioplasty. CASE
      REPORT: We report our experience in the management of a reduction en masse of a
      direct inguinal hernia. The diagnosis was established by computed tomography of
      the abdomen. The reduction en masse, as well as an accompanying indirect hernia,
      was successfully managed with laparoscopic transabdominal preperitoneal
      hernioplasty. CONCLUSION: The safety, effectiveness, and minimal invasiveness
      conferred by the laparoscopic approach justified its application under such
      conditions.

PMID- 22383216
TI  - The impact of pancreatic duct drainage following pancreaticojejunostomy on
      clinical outcome.
AB  - BACKGROUND: The aim of this meta-analysis is to evaluate the effect of stenting
      the pancreatic duct during pancreaticojejunostomy formation on perioperative
      outcomes. METHODS: Primary outcome measures were operative mortality and
      pancreatic fistula. Secondary outcomes were length of hospital stay, reoperation,
      delayed gastric emptying, estimated blood loss, and length of operation. Internal
      and external pancreatic stents were grouped together for the purposes of
      analysis. RESULTS: Six trials were included in this analysis comprising 732
      patients. Pancreatic stent placement had no significant effect on operative
      mortality; however, there was a non-significant trend towards reduced pancreatic
      fistula. Estimated blood loss, length of operation, and length of hospital stay
      were significantly increased in association with pancreatic stent placement.
      There were no significant effects on reoperation or delayed gastric emptying.
      CONCLUSION: This analysis demonstrates a trend towards reduced pancreatic fistula
      with the use of pancreatic stents in pancreaticojejunostomy. However, there were
      insufficient data to confidently reject the null hypothesis that stenting has no
      beneficial effect. Further research is required to identify whether in certain
      subgroups, such as those with soft pancreatic texture and a non-dilated duct,
      stents may have a more important role in reducing fistula formation.

PMID- 22383217
TI  - Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias
      by upregulating iGluRs in rats with healed myocardial necrotic injury.
AB  - Sympathetic nerve sprouting in healed myocardial infarction (MI) has been
      associated with high incidences of lethal arrhythmias, but the underlying
      mechanisms are largely unknown. This study sought to test that sympathetic
      hyperinnervation and/or MI remodels the myocardial glutamate signaling and
      ultimately increases the severity of ventricular tachyarrhythmias. Myocardial
      necrotic injury (MNI) was created by liquid nitrogen freeze-thawing across an
      intact diaphragm to mimic MI. Cardiac sympathetic hyperinnervation was induced by
      chronic subcutaneous injection of 4-methylcatechol, a potent stimulator of nerve
      growth factor expression. The results showed that sympathetic hyperinnervation
      with or without MNI upregulated the myocardial expression of ionotropic glutamate
      receptors (iGluRs), including NMDA receptor (NMDAR) and AMPA receptor (AMPAR),
      and induced cardiomyocyte apoptosis. Intravenous infusion with either NMDA (12
      mg/kg) or AMPA (15 mg/kg) triggered ventricular tachycardia and ventricular
      fibrillation in rats with healed MNI plus sympathetic hyperinnervation; these
      arrhythmias were prevented by respective antagonist of NMDAR or AMPAR. We
      conclude that MNI with sympathetic nerve sprouting upregulates the expression of
      NMDAR and AMPAR in the myocardium and this impact in turn enhances cardiac
      responses to stimulations of iGluRs and thus increases the incidence of
      ventricular tachyarrhythmias.

PMID- 22383218
TI  - Screening of congenital heart disease patients using multiplex ligation-dependent
      probe amplification: early diagnosis of syndromic patients.
AB  - Recurrent copy number variants (CNVs) are found in a significant proportion of
      patients with congenital heart disease (CHD) and some of these CNVs are
      associated with other developmental defects. In some syndromic patients, CHD may
      be the first presenting symptom, thus screening of patients with CHD for CNVs in
      specific genomic regions may lead to early diagnosis and awareness of
      extracardiac symptoms. We designed a multiplex ligation-dependent probe
      amplification (MLPA) assay specifically for screening of CHD patients. The MLPA
      assay allows for simultaneous analysis of CNVs in 25 genomic regions previously
      associated with CHD. We screened blood samples from 402 CHD patients and
      identified 14 rare CNVs in 13 (3.2%) patients. Five CNVs were de novo and six
      where inherited from a healthy parent. The MLPA screen led to early syndrome
      diagnosis in two of these patients. We conclude that the MLPA assay detects
      clinically relevant CNVs and suggest that it could be used within pediatric
      cardiology as a first tier screen to detect clinically relevant CNVs and identify
      syndromic patients at an early stage.

PMID- 22383219
TI  - Using time-to-onset for detecting safety signals in spontaneous reports of
      adverse events following immunization: a proof of concept study.
AB  - PURPOSE: Disproportionality analyses (DPA) are widely used in pharmacovigilance
      for detecting safety signals from spontaneous reports of adverse events. In these
      analyses, time-to-onset (TTO; the time between vaccination and the onset of the
      adverse event) is rarely considered. Our objective is to assess the potential use
      of TTO to improve signal detection (SD). METHODS: Adverse events were defined as
      signals for a vaccine if the TTO distribution was significantly different from
      the distribution of other events for the same vaccine and from the distribution
      obtained with the same event for other vaccines. Distributions were compared
      within a time window of 30 days by using the two-sample Kolmogorov-Smirnov
      statistic. With the use of the product label as a proxy of true positive safety
      signals, TTO SD was compared with a standard DPA method (based on stratified
      empirical Bayesian geometric mean) for an oral live pediatric vaccine (RotarixTM)
      and an inactivated adult vaccine (FluarixTM). RESULTS: With the use of the
      GlaxoSmithKline spontaneous reports database for RotarixTM, 10 Medical Dictionary
      for Regulatory Activities preferred terms were identified as signals, and among
      them, five were listed in the product label. The DPA method identified only three
      preferred terms from the label, that is, TTO SD showed higher sensitivity and
      specificity. For FluarixTM, TTO SD also showed higher sensitivity but lower
      specificity. CONCLUSION: This TTO SD method is complementary, conceptually and
      practically, to more traditional DPA and does not share the major drawback of DPA
      known as the masking effect. Higher sensitivity and/or specificity can be
      achieved using TTO SD.

PMID- 22383221
TI  - Contagious cancer: lessons from the devil and the dog.
AB  - Cancer is generally defined as uncontrollable growth of cells caused by genetic
      aberrations and/or environmental factors. Yet contagious cancers also occur. The
      recent emergence of a contagious cancer in Tasmanian devils has reignited
      interest in transmissible cancers. Two naturally occurring transmissible cancers
      are known: devil facial tumour disease and canine transmissible venereal tumour.
      Both cancers evolved once and have then been transmitted from one individual to
      another as clonal cell lines. The dog cancer is ancient; having evolved more than
      6,000 years ago, while the devil disease was first seen in 1996. In this review I
      will compare and contrast the two diseases focusing on the life histories of the
      clonal cell lines, their evolutionary trajectories and the mechanisms by which
      they have achieved immune tolerance. A greater understanding of these contagious
      cancers will provide unique insights into the role of the immune system in
      shaping tumour evolution and may uncover novel approaches for treating human
      cancer.

PMID- 22383222
TI  - Differential effects of nitrogen and sulfur deprivation on growth and biodiesel
      feedstock production of Chlamydomonas reinhardtii.
AB  - Biodiesel production from microalgae is a promising approach for energy
      production; however, high cost of its process limits the use of microalgal
      biodiesel. Increasing the levels of triacylglycerol (TAG) levels, which is used
      as a biodiesel feedstock, in microalgae has been achieved mainly by nitrogen
      starvation. In this study, we compared effects of sulfur (S) and nitrogen (N)
      starvation on TAG accumulation and related parameters in wild-type Chlamydomonas
      reinhardtii CC-124 mt(-) and CC-125 mt(+) strains. Cell division was interrupted,
      protein and chlorophyll levels rapidly declined while cell volume, total neutral
      lipid, carotenoid, and carbohydrate content increased in response to nutrient
      starvation. Cytosolic lipid droplets in microalgae under nutrient starvation were
      monitored by three-dimensional confocal laser imaging of live cells. Infrared
      spectroscopy results showed that relative TAG, oligosaccharide and polysaccharide
      levels increased rapidly in response to nutrient starvation, especially S
      starvation. Both strains exhibited similar levels of regulation responses under
      mineral deficiency, however, the degree of their responses were significantly
      different, which emphasizes the importance of mating type on the physiological
      response of algae. Neutral lipid, TAG, and carbohydrate levels reached their peak
      values following 4 days of N or S starvation. Therefore, 4 days of N or S
      starvation provides an excellent way of increasing TAG content. Although increase
      in these parameters was followed by a subsequent decline in N-starved strains
      after 4 days, this decline was not observed in S-starved ones, which shows that S
      starvation is a better way of increasing TAG production of C. reinhardtii than N
      starvation.

PMID- 22383223
TI  - Challenges and opportunities in neuroscience research.

PMID- 22383227
TI  - Effect of gender on late-onset multiple sclerosis.
AB  - OBJECTIVES: We aimed to examine the incidence and disease course of late-onset
      multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic
      cohort, stratified based on gender and race, since both have been reported as
      important modifiers of disease outcomes in MS. METHODS: Patients with LOMS and
      AOMS were compared in terms of demographic characteristics and disease course
      characteristics. Combined effects were investigated with a logistic regression
      model. Time from disease onset to sustained Expanded Disability Status Scale
      (EDSS) score of 6 was investigated using an extension of log-rank test
      appropriate for interval-censored data. RESULTS: Some 7.96% of 4273 patients
      studied had an onset of MS after the age of 50 years (LOMS), and 1.33%
      experienced an onset after age 60. Progressive onset was more common in LOMS
      relative to AOMS. The proportion of women with progressive-onset disease was
      similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared
      with males; however, it was similar between males and females in the LOMS group.
      CONCLUSIONS: Women with LOMS have a different trajectory in terms of disease
      progression than women with AOMS. The effect of menopause combined with
      race/ethnicity on the MS disease course requires further investigation.

PMID- 22383229
TI  - Natalizumab-associated central nervous system lymphoma?--another patient.

PMID- 22383228
TI  - A prospective, randomized, controlled trial of autologous haematopoietic stem
      cell transplantation for aggressive multiple sclerosis: a position paper.
AB  - BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has been tried in the
      last 15 years as a therapeutic option in patients with poor-prognosis autoimmune
      disease who do not respond to conventional treatments. Worldwide, more than 600
      patients with multiple sclerosis (MS) have been treated with HSCT, most of them
      having been recruited in small, single-centre, phase 1-2 uncontrolled trials.
      Clinical and magnetic resonance imaging outcomes from case series reports or
      Registry-based analyses suggest that a major response is achieved in most
      patients; quality and duration of response are better in patients transplanted
      during the relapsing-remitting phase than in those in the secondary progressive
      stage. OBJECTIVES: An interdisciplinary group of neurologists and haematologists
      has been formed, following two international meetings supported by the European
      and American Blood and Marrow Transplantation Societies, for the purpose of
      discussing a controlled clinical trial, to be designed within the new scenarios
      of evolving MS treatments. CONCLUSIONS: Objectives of the trial, patient
      selection, transplant technology and outcome assessment were extensively
      discussed. The outcome of this process is summarized in the present paper, with
      the goal of establishing the background and advancing the development of a
      prospective, randomized, controlled multicentre trial to assess the clinical
      efficacy of HSCT for the treatment of highly active MS.

PMID- 22383230
TI  - Characteristics of multiple sclerosis in aboriginals living in British Columbia,
      Canada.
AB  - OBJECTIVES: The objectives of this study were to identify and describe the
      demographic and clinical characteristics of multiple sclerosis (MS) in
      aboriginals in British Columbia (BC), Canada and compare these findings with non
      aboriginal MS patients. METHODS: This retrospective chart and database review
      accessed patient information from the linked BC-wide MS clinical and genetics
      databases. Data gathered included: demographics (age, sex and ethnicity);
      clinical characteristics (MS onset date, disease course and disability scores
      (Expanded Disability Status Scale [EDSS]). Aboriginals were identified via the
      database linkage augmented by physician and nurse recall. Two non-aboriginal
      comparator groups with definite MS were selected. Group one included all definite
      MS patients in the BC MS database, and group two comprised MS patients matched by
      sex, age at onset and initial disease course. Patient characteristics were
      compared using the Student's t-test, chi-squared test, and Kaplan-Meier survival
      analysis was used to examine disease progression (time to sustained and confirmed
      EDSS 6) RESULTS: We identified 26 aboriginals with MS, of which 19/26 (73%) were
      female, 23/26 (89%) had relapsing-onset MS and a mean onset age of 31.1 years.
      There were no significant differences between the MS aboriginals and the non
      matched (n = 5708) comparator group with respect to age, sex or disease course (p
      > 0.1), However, aboriginals progressed more rapidly to EDSS 6 from disease onset
      (p < 0.001) when compared with the matched and unmatched comparator groups.
      CONCLUSION: We identified a small, but important cohort of aboriginals with MS;
      being the largest identified to date. There was evidence of more rapid MS
      progression in aboriginals compared with non-aboriginals.

PMID- 22383231
TI  - Behavioural symptoms and impairments in multiple sclerosis: a systematic review
      and meta-analysis.
AB  - Behavioural problems are not well recognized in multiple sclerosis (MS). In this
      review we aimed to evaluate the prevalence of behavioural symptoms and
      impairments in MS. A systematic search was carried out from MEDLINE, PsycINFO,
      Web of Science, CINAHL and COCHRANE. In total, 23 studies (1831 participants)
      were identified. Based on the literature search, behavioural symptoms and
      impairments are observed in MS. Aggression (23%), apathy (22%), euphoria (12%)
      and lack of insight (11%) were the most frequent symptoms, and adjustment
      disorder (17%) the most frequent impairment. Severe mental disorders are more
      infrequent than changes in behaviour, manner of reaction, and way of action. In
      conclusion the objective behavioural impairments and especially subjective
      symptoms are present in patients with MS. These manifestations should be taken
      into account in the diagnostics and treatment of the disease.

PMID- 22383232
TI  - Natalizumab discontinuation after PML risk stratification: outcome from a shared
      and informed decision.
AB  - Multifocal progressive leukoencephalopathy (PML) is associated with JC virus
      (JCV) seropositivity, past immunosuppression, and natalizumab treatment for two
      years or more. The aim of our study was to investigate the rate of treatment
      discontinuation after stratifying for the three risk factors in a group of 104
      natalizumab-treated patients with relapsing-remitting multiple sclerosis. We
      investigated JCV serological status in our population. We then divided patients
      into groups according to their PML risk. Treatment indication was reassessed. Of
      the patients, 64 (61.5%) were JCV seropositive. Amongst seropositive patients on
      natalizumab for 2 years or more, 10 had received immunosuppression (group A), and
      38 had not (group B). After an informed and shared decision-making process, 6/10
      (60%) from group A compared with 9/38 (23.7%) from group B discontinued treatment
      (p=0.027). In groups A and B, discontinuation also depended upon doctors' views
      (p=0.019, group A; p=0.010, group B) and clinical outcomes (p=0.021, group A). No
      one from low-intermediate risk groups discontinued. The decision to discontinue
      natalizumab treatment is complex, even when clear PML risk rates are described.
      Clinical outcomes and doctors' idiosyncrasies play a crucial part in patients'
      final choice.

PMID- 22383233
TI  - Curative embolization of brain arteriovenous malformations with onyx: patient
      selection, embolization technique, and results.
AB  - BACKGROUND AND PURPOSE: A new curative embolization technique with Onyx for
      selected small and medium-sized superficially located brain AVMs was developed,
      which consists of obliteration of the nidus, including incremental occlusion of
      the draining veins. We report our first clinical results. MATERIALS AND METHODS:
      Between June 2008 and July 2011, 24 patients (7 women, 17 men; mean age, 41
      years; range, 6-74 years) with AVMs were selected for curative embolization with
      Onyx. Presentation was hemorrhage in 14 and seizures in 10 patients. AVM location
      was frontal in 11, occipital in 6, parietal in 4, and temporal in 3. AVM size was
      a mean of 2.2 cm (median, 2; range, 1-3 cm). RESULTS: Complete angiographic
      obliteration of the AVM with Onyx in a single session was achieved in all 24
      patients. There were no hemorrhagic or ischemic complications (0%; 95% CI, 0%
      16.3%), and no new deficits induced by the treatment. Of 14 patients with
      ruptured AVMs, 1 patient who presented with a large frontal hematoma died shortly
      after surgical evacuation of the hematoma following complete embolization of a
      micro-AVM. Follow-up angiography at 3 months in 23 patients demonstrated a small
      AVM remnant in 1 that was treated with gamma knife radiosurgery. The other 22
      AVMs remained completely occluded. CONCLUSIONS: In selected patients with small
      and medium-sized superficial brain AVMs, as defined in our study, injection of
      Onyx by using a curative embolization technique in a single session seems to
      provide a safe and effective alternative to radiosurgery or surgery.

PMID- 22383234
TI  - White matter alterations in cognitively normal apoE epsilon2 carriers: insight
      into Alzheimer resistance?
AB  - BACKGROUND AND PURPOSE: The basis for decreased vulnerability to AD among apoE
      epsilon2 carriers is unknown. The purpose of this study was to use diffusion
      tensor imaging to detect possible differences in white matter integrity between
      cognitively normal elderly apoE epsilon2 carriers and apoE epsilon3/epsilon3
      controls. MATERIALS AND METHODS: Thirty-nine cognitively normal elderly
      individuals (19 heterozygous carriers of the apoE epsilon2 allele, 20 apoE
      epsilon3/epsilon3 subjects as controls) underwent diffusion tensor MR imaging on
      a 4T scanner. Fractional anisotropy, MD, and axial and radial diffusivity were
      compared using a ROI approach. In addition, an exploratory whole-brain analysis
      of fractional anisotropy between the 2 groups was undertaken using TBSS. RESULTS:
      apoE epsilon2 carriers had higher FA in the posterior cingulate white matter (P =
      .01) and anterior corpus callosum (P = .005) than apoE epsilon3/epsilon3
      controls, secondary to lower radial diffusivity. No significant differences in
      the FA of the posterior corpus callosum, anterior cingulate white matter, or
      parahippocampal white matter were seen. Whole-brain TBSS analysis detected
      regions of higher FA in the apoE epsilon2 group in the superior longitudinal
      fasciculus, right thalamus, and the bilateral anterior limbs of the internal
      capsule, in addition to the posterior cingulum and corpus callosum (P < .005).
      There were no regions in which the apoE epsilon3/epsilon3 group had higher FA.
      CONCLUSIONS: apoE epsilon2 carriers harbor more robust white matter integrity
      that may be associated with decreased vulnerability to developing AD. This
      provides further evidence that regional DTI metrics may serve as early imaging
      biomarkers of AD risk.

PMID- 22383235
TI  - Multimodality MR imaging findings of low-grade brain edema in hepatic
      encephalopathy.
AB  - HE is a neuropsychiatric syndrome that develops in patients with severe liver
      diseases, with portosystemic shunt surgery in the form of diffuse mild brain
      edema. It is also associated with functional changes, such as those in attention
      and the DMN. MR imaging offers a range of capabilities for assessing the low
      grade brain edema and its functional changes in brain affected by HE; therefore,
      it provides the opportunity to uncover the pathophysiologic mechanisms of HE.
      This article will review our current understanding of the pathophysiology of low
      grade brain edema and will outline the role of structural MR imaging, MTR, DWI,
      DTI, and MR spectroscopy in the detection of low-grade brain edema, and the role
      of BOLD fMRI in the exploration of the related functional changes. A perspective
      of the study in this area will also be provided.

PMID- 22383236
TI  - Diffusion tensor-MRI evidence for extra-axonal neuronal degeneration in caudate
      and thalamic nuclei of patients with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: MS is an inflammatory demyelinating disease affecting
      both WM and GM. While WM lesions are easily visualized by conventional MR
      imaging, the detection of GM alterations remains challenging. This diffusion
      tensor MR imaging study aimed to detect and characterize diffuse microscopic
      alterations in 2 deep GM structures, the caudate nucleus and the thalamus, in
      patients with RR and SP MS. The relationship between diffusivity markers, and
      atrophy of the caudate and the thalamus, as well as brain lesion load and
      clinical status of the patients was also explored. MATERIALS AND METHODS: Twenty
      three RR and 18 SP patients, along with 27 healthy controls, underwent MR imaging
      examination including anatomic and DTI acquisitions. Volumes, mean FA, and MD of
      the caudate and the thalamus, as well as WM lesion volumes, were assessed.
      RESULTS: FA was significantly (P < .001) increased in the caudate and the
      thalamus of patients with MS compared with controls, and was higher in SP
      compared with RR patients. Increased FA was associated with volume decreases of
      caudate (r = -0.712; P < .001) and thalamus (r = -0.407; P < .01) in patients
      with MS. WM T2 lesion load was significantly associated with caudate (r = 0.611;
      P < .001) and thalamic (r = 0.354; P < .05) FA. Caudate FA, and, to a lesser
      extent, thalamic FA, were associated with functional deficits, as measured by
      EDSS and MSFC. CONCLUSIONS: Increased FA in the caudate and the thalamus may
      constitute a sensitive marker of MS pathologic processes, such as loss of
      dendrites and/or swelling of neuronal cell bodies.

PMID- 22383237
TI  - Does higher gadolinium concentration play a role in the morphologic assessment of
      brain tumors? Results of a multicenter intraindividual crossover comparison of
      gadobutrol versus gadobenate dimeglumine (the MERIT Study).
AB  - BACKGROUND AND PURPOSE: Gadobenate dimeglumine has proved advantageous compared
      with other gadolinium-based contrast agents for contrast-enhanced brain MR
      imaging. Gadobutrol is a more highly concentrated agent (1.0 mol/L). This study
      intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and
      quantitative evaluation of brain tumors. MATERIALS AND METHODS: Adult patients
      with suspected or known brain tumors underwent 2 identical MR imaging
      examinations at 1.5T, 1 with gadobenate dimeglumine and the other with
      gadobutrol, both at a dose of 0.1-mmol/kg body weight. The agents were injected
      in randomized order separated by 3-14 days. Imaging sequences and acquisition
      timing were identical for the 2 examinations. Three blinded readers evaluated
      images qualitatively for diagnostic information (lesion extent, delineation,
      morphology, enhancement, global preference) and quantitatively for CNR and LBR.
      RESULTS: One hundred fourteen of 123 enrolled patients successfully underwent
      both examinations. Final diagnoses were intra-axial tumors, metastases, extra
      axial tumors, "other" tumors, and "nontumor" (49, 46, 8, 7, and 4 subjects,
      respectively). Readers 1, 2, and 3 demonstrated preference for gadobenate
      dimeglumine in 46 (40.7%), 54 (47.4%), and 49 (43.0%) patients, respectively,
      compared with 6, 7, and 7 patients for gadobutrol (P < .0001, all readers).
      Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine
      was demonstrated for all other qualitative end points. Inter-reader agreement was
      good for all evaluations (kappa = 0.414-0.629). Significantly superior CNR and
      LBR were determined for gadobenate dimeglumine (P < .019, all readers).
      CONCLUSIONS: Significantly greater morphologic information and lesion enhancement
      are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared
      with gadobutrol at an equivalent dose.

PMID- 22383238
TI  - Malignant CTA collateral profile is highly specific for large admission DWI
      infarct core and poor outcome in acute stroke.
AB  - BACKGROUND AND PURPOSE: Large admission DWI lesion volumes are associated with
      poor outcomes despite acute stroke treatment. The primary aims of our study were
      to determine whether CTA collaterals correlate with admission DWI lesion volumes
      in patients with AIS with proximal occlusions, and whether a CTA collateral
      profile could identify large DWI volumes with high specificity. MATERIALS AND
      METHODS: We studied 197 patients with AIS with M1 and/or intracranial ICA
      occlusions. We segmented admission and follow-up DWI lesion volumes, and
      categorized CTA collaterals by using a 5-point CS system. ROC analysis was used
      to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were
      dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate
      and multivariate analyses were performed to compare imaging and clinical
      variables between these 2 groups. RESULTS: There was a negative correlation
      between CS and admission DWI lesion volume (rho = -0.54, P < .0001). ROC analysis
      revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC =
      0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI
      volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL
      versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001),
      and were more likely to become functionally dependent at 3 months (95.5% versus
      64.0%, P = .003). Admission NIHSS score was the only independent predictor of a
      malignant CS (P = .007). CONCLUSIONS: In patients with AIS with PAOs, CTA
      collaterals correlate with admission DWI infarct size. A malignant collateral
      profile is highly specific for large admission DWI lesion size and poor
      functional outcome.

PMID- 22383239
TI  - Reduced-distortion diffusion MRI of the craniovertebral junction.
AB  - BACKGROUND AND PURPOSE: CVJ lesion suffers from a high sensitivity to
      susceptibility and distortion artifacts, which sometimes makes diffusion image
      difficult to interpret. Our purpose was to evaluate the potential for diffusion
      MR imaging using RS-EPI compared with SS-EPI in the assessment of the CVJ.
      MATERIALS AND METHODS: RS-EPI and SS-EPI DTI images were acquired from 10 healthy
      volunteers using 3T MRI with a 32-channel head coil. For both sequences, the
      following parameters were used: 1-mm(2) in-plane resolution; 3-mm section
      thickness; TR = 5200 ms; 1 acquisition at b = 0 and 12 different encoding
      directions at b = 1000 seconds/mm(2). The RS-EPI sequence scan time was 9.44
      minutes (1 average). The SS-EPI sequence was 9.37 minutes (8 averages). Diffusion
      tensor calculation and image analysis were performed using DTIStudio software.
      Diffusion trace images and color-coded fiber orientation maps were evaluated by 2
      independent readers for distortion and delineation of fine structure using a
      semiquantitative scale in selected landmark locations. The absolute distances
      between the temporal base and the cerebellar contour between the T2-weighted
      images and the diffusion trace images obtained with RS-EPI and SS-EPI were also
      compared. RESULTS: The contours of the temporal lobe and cerebellum were better
      delineated and distortion artifacts were clearly reduced with the RS-EPI
      sequence. More fine structures were also visible in the brain stem and cerebellum
      with the RS-EPI sequence. The amount of distortion was significantly reduced with
      RS-EPI compared with SS-EPI (P < .01). CONCLUSIONS: The RS-EPI DTI sequence was
      less prone to geometric distortion than the SS-EPI sequence and allowed a better
      delineation of CVJ internal structure. Although the acquisition time is still
      relatively long, the RS-EPI appears as a promising approach to perform DTI
      studies in CVJ lesions, such as brain stem ischemia, neurodegenerative diseases,
      brain and skull base tumors, or inflammation.

PMID- 22383240
TI  - Spectrum of MR imaging findings in Wernicke encephalopathy: are atypical areas of
      involvement only present in nonalcoholic patients?
AB  - BACKGROUND AND PURPOSE: Although MR imaging is considered the most effective
      method to confirm a diagnosis of WE, MR imaging studies designed to distinguish
      WE between NA and AL patients have yielded controversial results. The purpose of
      this study was to determine potential differences in MR imaging features between
      AL and NA patients with WE and to compare neurologic symptoms with MR imaging
      findings. MATERIALS AND METHODS: This retrospective study included 24 consecutive
      patients (male/female, 15:9; mean age, 54 years) diagnosed with WE in a
      university hospital (AL = 13, NA = 11). Clinical manifestations and MR imaging
      findings between AL and NA patients were evaluated. Classic WE symptom triad and
      consciousness level and MR imaging findings were scored and compared with each
      other. Statistical analyses were performed with chi(2), Fisher exact, and
      Spearman tests. RESULTS: No differences were observed regarding the areas of
      hyperintense signal intensity on FLAIR imaging and enhancement of the mammillary
      bodies between AL and NA patients (P > .05). Frequent sites of involvement were
      the medial thalami (86%), dorsal medulla (82%), tectal plate (77%), and the
      periaqueductal gray matter (75%). A positive association was found between the
      consciousness levels of the patients and the involvement of atypical sites (P =
      .01). Only 4 of the 24 patients (17%) had all 3 symptoms of the classic WE
      symptom triad. CONCLUSIONS: MR imaging features of WE may not be different
      between AL and NA patients. The medulla is 1 of the most frequently involved
      sites, and consciousness level is also associated with atypical site involvement.

PMID- 22383241
TI  - Active bleeding in acute subarachnoid hemorrhage observed by multiphase dynamic
      enhanced CT.
AB  - BACKGROUND AND PURPOSE: Acute SAH is reportedly associated with rebleeding from
      aneurysms, and recent advances in imaging technology allow us to visualize active
      bleeding in SAH cases. This study aimed to retrospectively investigate the
      incidence and characteristics of active bleeding in patients with spontaneous SAH
      by using multiphase dynamic-enhanced CT. MATERIALS AND METHODS: We
      retrospectively surveyed a series of patients with SAH who underwent CTP with 18
      phase dynamic enhancement and confirmed the presence of extravasated contrast
      medium in the source image. We compared clinical features between 2 groups of
      patients with and without extravasation. RESULTS: Active bleeding was observed
      with increasing enhancement in 25.5% (13/51) of patients. All patients with
      extravasation were in Claassen grade 3 or 4 and WFNS grades 3, 4, or 5. The other
      group without extravasation included patients in all grades. A significant
      difference was observed in Claassen grade, WFNS grade, and increase of hematomas
      in follow-up CT (P < .05, for each) between the 2 groups. All CTP results of
      patients with extravasation were obtained within 2 hours of the onset of symptoms
      of SAH (P < .05). There was no significant difference in mortality at 14 days
      between the 2 groups (P = .128). CONCLUSIONS: A high incidence of active bleeding
      (25.5%) was detected by multiphase dynamic-enhanced CT in patients with acute
      SAH. These results indicate that an awareness of active bleeding in patients with
      SAH has the potential to affect the treatment strategy.

PMID- 22383242
TI  - Brain volume and diffusion markers as predictors of disability and short-term
      disease evolution in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: MRI markers of neuroaxonal damage in MS have emerged as
      critical long-term predictors of MS-related disability. Here we investigated the
      potential of whole-brain diffusivity and brain volume for the prediction of cross
      sectional disability and short- to medium-term clinical evolution. MATERIALS AND
      METHODS: In this multimodal prospective longitudinal MRI study of 54 patients
      with MS (87% under immunomodulatory therapy, baseline and follow-up at a median
      of 12 months), ADC histogram analysis, WM lesion load, BPF, whole-brain atrophy
      rate, MSFC score, and EDSS score were obtained. A total of 44 patients with no
      relapse at both time points were included. RESULTS: At both time points, ADC
      histogram analysis provided robust predictors of the MSFC scores (maximal R(2) =
      0.576, P < .001), incorporated cognition and fine-motor skill subscores, and EDSS
      scores. Significant changes beyond physiologic age-related changes at follow-up
      were noted for ADC histogram markers and BPF. Stronger diffusivity alterations
      and brain volume at baseline predicted MSFC decline, as demonstrated by multiple
      linear regression analysis (mean ADC, R(2) = 0.203; P = .003) and lower baseline
      BPF in patients with declined compared with stable MSFC scores (P = .001).
      Results were independent of intercurrent relapses. CONCLUSIONS: Diffusion
      histogram analysis provided stable surrogates of disability in MS and proved
      sensitive for monitoring disease progression during a median of 12 months.
      Advanced neuroaxonal pathology at baseline was indicative of an increased risk
      for sustained progression during a median of 12 months, independent of
      intercurrent relapses.

PMID- 22383243
TI  - Local thrombolysis for severe cerebral venous sinus thrombosis.
AB  - BACKGROUND AND PURPOSE: Cerebral venous thrombosis is a rare entity that can be
      difficult to manage. Most patients with cerebral sinus thrombosis recover after
      treatment with heparin, but a subgroup of severe cerebral venous sinus thrombosis
      has a poor prognosis. Those patients may benefit from intrasinus thrombolysis.
      The purpose of this research was to carry out a retrospective analysis of
      patients with severe cerebral venous sinus thrombosis, and to study the safety
      and efficacy of intrasinus thrombolysis in patients with cerebral venous sinus
      thrombosis unresponsive to conventional heparin therapy. MATERIALS AND METHODS:
      Thirty-seven patients with cerebral venous sinus thrombosis who received
      intrasinus thrombolysis during a 3-year period (January 2007 to December 2009)
      were included in this study. Urokinase was infused into the sinus via a
      microcatheter. Data regarding demographic, clinical, and radiologic features were
      collected. Follow-up data were obtained at 6 months. MRV was repeated to assess
      the recanalization of the venous sinus. RESULTS: Twenty-seven patients (73%) had
      good outcome and 7 patients (19%) who were independent for activities of daily
      life had only mild deficits. One patient survived with severe neurologic deficits
      and 2 patients died. Complete recanalization of the superior sagittal sinus was
      seen in 35 patients (97%). At a follow-up of 6 months, 34 patients (92%) were
      either asymptomatic or had only minor subjective symptoms. CONCLUSIONS:
      Intrasinus thrombolysis is safe and effective in patients with severe cerebral
      venous sinus thrombosis. However, the subgroup of patients that is likely to
      benefit the most from this procedure is not clear from our data. Large randomized
      controlled trials are required to further clarify this issue.

PMID- 22383244
TI  - The JAK2V617F tyrosine kinase mutation has no impact on overall survival and the
      risk of leukemic transformation in myelofibrosis.
AB  - The prevalence of JAK2V617F tyrosine kinase mutation differs between various
      variants of myelofibrosis with the higher detection rate for patients with post
      polycythemia vera myelofibrosis (post-PV MF; 91%) if compared to primary
      myelofibrosis (PMF; 45%) and post-essential thrombocythemia myelofibrosis (post
      ET MF; 39%). The impact of V617F point mutation and its allele burden on overall
      survival (OS) and the risk of leukemic transformation (LT) has been the subject
      of several studies, but the results were ambiguous. Our study included 77
      patients with the following variants: 42 patients with PMF (55%), 16 with post-ET
      MF (21%) and 19 with post-PV MF (24%). Median age at diagnosis for the entire
      cohort was 61 years (range 19-81), with 53% of female. A total of 42 patients
      were JAK2V617F positive, giving an overall frequency of 55%; the median allele
      burden was 22% (range 2-96%). The JAK2V617F point mutation was detected in 21
      patients with PMF (50%), 14 with post-PV MF (88%) and 7 with post-ET MF (37%).
      Lower JAK2V617F allele burden was more frequently detected in PMF patients,
      whereas higher allele burden was predominantly seen in post-PV/ET MF group. There
      was no significant difference between V617F-positive and V617F-negative patients
      in terms of studied parameters in PMF as well as in post-PV/ET MF subgroup. No
      significant difference was also demonstrated when the above-mentioned
      subpopulations were analyzed according to JAK2V617F allele burden, except higher
      leukocyte count in post-PV/ET MF patients with higher allele burden (14.3*10(9)/L
      vs. 6.2*10(9)/L; p=.03). Median follow-ups for V617F-positive and V617F-negative
      patients were 16.6 months (range 3.6-206.4) and 36.4 months (range 2.5-142.1),
      respectively. The presence of JAK2V617F mutation did not affect OS and the risk
      of LT development.

PMID- 22383246
TI  - Balanced complex chromosome rearrangements: reproductive aspects. A review.
AB  - This review examines the reproductive consequences for carriers of a balanced
      complex chromosome rearrangement (CCR). It is based on an analysis of CCRs in 103
      adults referred for reproductive problems, including male infertility. The main
      focus is on reproductive risks based on data from 84 CCRs. Carriers of balanced
      CCRs have a high risk of an abortion and/or a chromosomally unbalanced child. I
      have identified roughly four different types of CCRs (I-IV); most (44%) belong to
      Type I with a simple 3-way or 4-way exchange of segments and risk factors similar
      to those for reciprocal translocations. There were only three CCRs (4%) of type
      II, which involve an inversion. Type III CCRs (21%) involve one or more
      insertions with ~35% risk of a child with a duplication or a deletion of the
      inserted segment. Type IV CCRs (31%) involve a "middle segment" in a derivative
      chromosome with segments from at least three chromosomes. In ~35% of these CCRs,
      recombination occurs in this segment, which can produce imbalance but in many
      cases it changes a CCR into a simpler balanced rearrangement in the next
      generation. Balanced CCRs, which have been often considered together in one
      group, can now be split into four types, each with a risk of a different type of
      imbalance. This analysis provides a better understanding of the reproductive
      consequences for carriers of balanced CCRs and should be useful in prenatal
      diagnosis and genetic counseling.

PMID- 22383247
TI  - Colorectal cancer incidence on the General Practice Research Database.
AB  - PURPOSE: The General Practice Research Database (GPRD) contains longitudinal
      patient medical records collected within UK primary care. This study aimed to
      identify incident cases of colorectal cancer on the GPRD and to compare incidence
      rates for 2007 with those reported by the UK cancer registries. METHODS:
      Algorithms were created to identify incident cases of colorectal cancer on the
      GPRD and cases were required to have additional medical codes to support the
      diagnosis. Age-specific and sex-specific incidence rates for 2007 were calculated
      using the GPRD data and compared with those reported by the cancer registries.
      RESULTS: Trends in colorectal cancer by age and sex were similar for the two data
      sources; however, the incidence of colorectal cancer on the GPRD was lower than
      that of the registries, particularly when supporting evidence was required: 57.0
      compared with 70.2 per 100 000 per year for men and 42.0 compared with 56.6 per
      100 000 per year for women. Inclusion of cases without supporting evidence still
      resulted in lower rates but increased the GPRD rates to 63.7 and 48.4 for men and
      women, respectively. The largest discrepancy was observed in the older age
      groups. CONCLUSION: Colorectal cancer rates on the GPRD were lower than those
      reported by UK cancer registries, especially when requiring supporting evidence
      in addition to a diagnosis code. It appears that the requirement of supporting
      evidence on the GPRD for colorectal cancer identification may result in some true
      cases being excluded, particularly in the very elderly. Copyright (c) 2012 John
      Wiley & Sons, Ltd.

PMID- 22383248
TI  - Metabolic engineering of Lactobacillus casei for production of UDP-N
      acetylglucosamine.
AB  - UDP-sugars are used as glycosyl donors in many enzymatic glycosylation processes.
      In bacteria UDP-N-acetylglucosamine (UDP-GlcNAc) is synthesized from fructose-6
      phosphate by four successive reactions catalyzed by three enzymes: Glucosamine-6
      phosphate synthase (GlmS), phosphoglucosamine mutase (GlmM), and the bi
      functional enzyme glucosamine-1-phosphate acetyltransferase/N-acetylglucosamine-1
      phosphate uridyltransferase (GlmU). In this work several metabolic engineering
      strategies, aimed to increment UDP-GlcNAc biosynthesis, were applied in the
      probiotic bacterium Lactobacillus casei strain BL23. This strain does not produce
      exopolysaccharides, therefore it could be a suitable host for the production of
      oligosaccharides. The genes glmS, glmM, and glmU coding for GlmS, GlmM, and GlmU
      activities in L. casei BL23, respectively, were identified, cloned and shown to
      be functional by homologous over-expression. The recombinant L. casei strain over
      expressing simultaneously the genes glmM and glmS showed a 3.47 times increase in
      GlmS activity and 6.43 times increase in GlmM activity with respect to the
      control strain. Remarkably, these incremented activities resulted in about
      fourfold increase of the UDP-GlcNAc pool. In L. casei BL23 wild type strain
      transcriptional analyses showed that glmM and glmU are constitutively
      transcribed. By contrast, glmS transcription is down-regulated with a 21-fold
      decrease of glmS mRNA in cells cultured with N-acetylglucosamine as the sole
      carbon source compared to cells cultured with glucose. Our results revealed for
      the first time that GlmS, GlmM, and GlmU are responsible for UDP-GlcNAc
      biosynthesis in lactobacilli.

PMID- 22383249
TI  - Determination of the esculetin contents of medicinal plants by liquid
      chromatography-tandem mass spectrometry.
AB  - We developed a LC-MS/MS method for the determination of esculetin contents in
      medicinal plants. The analysis was performed using multiple reaction monitoring
      in negative mode, and an XBridgeTM C(18) column (2.1 * 100 mm, 3.5 um) was used.
      Methanol and 0.1% formic acid were used for gradient analysis. The calibration
      curve showed good linearity (r(2)  > 0.9993). The limits of detection and
      quantitation were 0.02 and 0.07 ng/mL, respectively. The intra-day and inter-day
      precisions were 1.5-6.8 and 2.0-5.3%, respectively, and the accuracy was 102.0
      110.2%. The contents of esculetin in 35 different plants were determined, and
      Fraxini Cortex showed the highest content of esculetin (761-5475 mg/kg). In Mori
      Folium and Artemisiae Capillaris Herba, 5.2-21.5 and 7.0-17.6 mg/kg of esculetin
      were found, respectively. In other medicinal plants, no esculetin was detected,
      or it was present at a concentration less than 10 mg/kg. The analysis method
      appears to be simple, sensitive and reproducible. Contrary to expectations based
      on traditional medical knowledge, although Artemisiae Capillaris Herba contains a
      large amount of esculetin, it appears from this study that Fraxini Cortex
      contains a greater amount. The pharmacological effects of esculetin isolated from
      medicinal plants should be investigated as part of new medicines development.

PMID- 22383250
TI  - Cytokine in new H1N1 influenza virus infection.

PMID- 22383252
TI  - A second case of contractures, webbed neck, micrognathia, hypoplastic nipples,
      and distinctive facial features: confirmation of the Dinno syndrome.
AB  - We report on a child with micrognathia, a short, webbed neck, joint contractures,
      hypoplastic nipples, and a number of other anomalies. There are striking
      similarities to a patient reported by [Dinno and Weisskopf (1976); Synd Ident,
      4:10-12], and we postulate that this child represents the second patient with
      this condition.

PMID- 22383251
TI  - Investigations on the 4-quinolone-3-carboxylic acid motif part 5: modulation of
      the physicochemical profile of a set of potent and selective cannabinoid-2
      receptor ligands through a bioisosteric approach.
AB  - Three heterocyclic systems were selected as potential bioisosteres of the amide
      linker for a series of 1,6-disubstituted-4-quinolone-3-carboxamides, which are
      potent and selective CB2 ligands that exhibit poor water solubility, with the aim
      of improving their physicochemical profile and also of clarifying properties of
      importance for amide bond mimicry. Among the newly synthesized compounds, a 1,2,3
      triazole derivative (1-(adamantan-1-yl)-4-[6-(furan-2-yl)-1,4-dihydro-4-oxo-1
      pentylquinolin-3-yl]-1H-1,2,3-triazole) emerged as the most promising in terms of
      both physicochemical and pharmacodynamic properties. When assayed in vitro, this
      derivative exhibited inverse agonist activity, whereas, in the formalin test in
      mice, it produced analgesic effects antagonized by a well-established inverse
      agonist. Metabolic studies allowed the identification of a side chain
      hydroxylated derivative as its only metabolite, which, in its racemic form, still
      showed appreciable CB2 selectivity, but was 150-fold less potent than the parent
      compound.

PMID- 22383254
TI  - Human health care and selection effects. Understanding labor supply in the market
      for nursing.
AB  - The aim of this paper is to study (adverse) selection in a labor supply model
      where potential applicants are characterized by different vocational levels and
      skills. We look at how the composition of the pool of active workers changes as
      the wage rate increases. Contrary to what would expect, average productivity does
      not necessarily increase monotonically in the wage rate. We identify conditions
      in which a wage increase reduces the average productivity and/or average vocation
      of active workers. Our results help understand the potential impact of wage
      increases as a policy designed to resolving shortages in the labor market for
      nurses.

PMID- 22383253
TI  - The carmaphycins: new proteasome inhibitors exhibiting an alpha,beta-epoxyketone
      warhead from a marine cyanobacterium.
AB  - Two new peptidic proteasome inhibitors were isolated as trace components from a
      Curacao collection of the marine cyanobacterium Symploca sp. Carmaphycin A (1)
      and carmaphycin B (2) feature a leucine-derived alpha,beta-epoxyketone warhead
      directly connected to either methionine sulfoxide or methionine sulfone. Their
      structures were elucidated on the basis of extensive NMR and MS analyses and
      confirmed by total synthesis, which in turn provided more material for further
      biological evaluations. Pure carmaphycins A and B were found to inhibit the beta5
      subunit (chymotrypsin-like activity) of the S. cerevisiae 20S proteasome in the
      low nanomolar range. Additionally, they exhibited strong cytotoxicity to lung and
      colon cancer cell lines, as well as exquisite antiproliferative effects in the
      NCI60 cell-line panel. These assay results as well as initial structural biology
      studies suggest a distinctive binding mode for these new inhibitors.

PMID- 22383256
TI  - Recognition between a short unstructured peptide and a partially folded fragment
      leads to the thioredoxin fold sharing native-like dynamics.
AB  - Thioredoxins (TRXs) constitute attractive alpha/beta scaffolds for investigating
      molecular recognition. The interaction between the recombinant fragment spanning
      the sequence 1-93 of full-length TRX (TRX1-93) and the synthetic peptide
      comprising residues 94-108 (TRX94-108), plus a C-terminal tyrosine tag (the
      numbering scheme used in entry pdb 2TRX is used throughout the article, two
      complementary moieties of E. coli TRX, brings about the consolidation of a native
      like complex. Despite its reduced thermodynamic stability, this complex is able
      to acquire fine structural features remarkably similar to those characteristic of
      full-length TRX, namely, hydrodynamic behavior, assessed by diffusion-ordered
      spectroscopy (DOSY)-NMR; the pattern of secondary structure, as revealed by three
      bond HNHalpha coupling constants and secondary shifts for Halpha/CO/Calpha/Cbeta;
      native-like tertiary structural signatures revealed by near-UV circular dichroism
      (CD) spectroscopy. The complex exhibits a relaxation behavior compatible with
      that expected for a native-like structure. However, heteronuclear nuclear
      Overhauser effect (NOE)s reveal an enhanced dynamics for the complex by
      comparison with full-length TRX. Furthermore, higher R(2) values for residues 43
      50 and 74-89 would likely result from an exchange process modulated by the
      peptide at the interface region. The slow kinetics of the consolidation reaction
      was followed by CD and real-time NMR. Equilibrium titration experiments by NMR
      yield a K(D) value of 1.4 +/- 1.0 MUM and a second low-affinity (>150 MUM)
      binding event in the vicinity of the active site. Molecular dynamics simulations
      of both the isolated fragment TRX1-93 and the complex suggest the destabilization
      of alpha2 and alpha3 helical elements and the persistence of beta-structure in
      the absence of TRX94-108. Altogether, structural and dynamic evidence presented
      herein points to the key role played by the C-terminal helix in establishing the
      overall fold. This critical switch module endows reduced TRX with the ability to
      act as a cooperative folding unit.

PMID- 22383257
TI  - Highly sensitive and rapid ultra-performance liquid chromatography-tandem mass
      spectrometry method for the determination of nifedipine in human plasma and its
      application to a bioequivalence study.
AB  - An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method has been developed for the determination of nifedipine in human plasma
      using nifedipine-d6 as the internal standard (IS). The plasma samples were
      prepared by solid-phase extraction on Phenomenex Strata-X cartridges employing
      200 MUL human plasma. Chromatography was carried out on Waters Acquity UPLC BEH
      C18 (50 * 2.1 mm, 1.7 um particle size) analytical column under isocratic
      conditions using a mobile phase consisting of 4.0 mm ammonium acetate
      acetonitrile (15:85, v/v). The precursor -> product ion transitions for
      nifedipine (m/z 347.2 -> 315.2) and IS (m/z 353.1 -> 318.1) were monitored on a
      triple quadrupole mass spectrometer, operating in the multiple reaction
      monitoring and positive-ion mode. The method was validated over a wide dynamic
      concentration range of 0.050-150 ng/mL. Matrix effect was assessed by post-column
      analyte infusion and the mean extraction recovery was 95.6% across four quality
      control levels. The method is rugged and rapid with a total run time of 1.2 min
      and was applied to a bioequivalence study of 20 mg nifedipine tablet formulation
      in 30 healthy Indian subjects under fasting condition. Assay reproducibility was
      confirmed by reanalysis of 116 incurred samples.

PMID- 22383258
TI  - Synthesis of simplified tedanolide analogues--connecting tedanolide to
      myriaporone and gephyronic acid.
AB  - Southern belles! Simplified analogues of tedanolide, a natural product with
      picomolar activity against a range of tumor cell lines, were synthesized and
      evaluated for potency in mammalian cancer cells. The truncated analogues were
      found to retain significant activity in vitro (23 MUmol mL(-1) for the example
      shown) compared with the parent compound tedanolide (0.33 nmol mL(-1)), and
      represent potential leads for the development of novel anticancer agents.

PMID- 22383259
TI  - A new and unexpected domain-domain interaction in the AraC protein.
AB  - An interaction between the dimerization domains and DNA binding domains of the
      dimeric AraC protein has previously been shown to facilitate repression of the
      Escherichia coli araBAD operon by AraC in the absence of arabinose. A new
      interaction between the domains of AraC in the presence of arabinose is reported
      here, the regulatory consequences of which are unknown. Evidence for the
      interaction is the following: the dissociation rate of arabinose-bound AraC from
      half-site DNA is considerably faster than that of free DNA binding domain, and
      the affinity of the dimerization domains for arabinose is increased when half
      site DNA is bound. In addition, an increase in the fluorescence intensity of
      tryptophan residues located in the arabinose-bound dimerization domain is
      observed upon binding of half-site DNA to the DNA binding domains. Direct
      physical evidence of the new domain-domain interaction is demonstrated by
      chemical crosslinking and NMR experiments.

PMID- 22383260
TI  - Cyclical absenteeism among private sector, public sector and self-employed
      workers.
AB  - This research note analyzes differences in the number of absent working days and
      doctor visits and in their cyclicality between private sector, public sector and
      self-employed workers. For this purpose, I used large-scale German survey data
      for the years 1995 to 2007 to estimate random effects negative binomial (count
      data) models. The main findings are as follows. (i) Public sector workers have on
      average more absent working days than private sector and self-employed workers.
      Self-employed workers have fewer absent working days and doctor visits than
      dependent employed workers. (ii) The regional unemployment rate is on average
      negatively correlated with the number of absent working days among private and
      public sector workers as well as among self-employed men. The correlations
      between regional unemployment rate and doctor visits are only significantly
      negative among private sector workers.

PMID- 22383261
TI  - Identification of 2 novel ANTXR2 mutations in patients with hyaline fibromatosis
      syndrome and proposal of a modified grading system.
AB  - Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are
      rare, autosomal recessive disorders of the connective tissue caused by mutations
      in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on
      chromosome 4q21. Characteristically, these conditions present with overlapping
      clinical features, such as nodules and/or pearly papules, gingival hyperplasia,
      flexion contractures of the joints, and osteolytic bone defects. The present
      report describes a pair of sibs and three other JHF/ISH patients whose diagnoses
      were based on typical clinical manifestations and confirmed by histopathologic
      analyses and/or molecular analysis. A comparison of ISH and JHF, additional
      thoughts about new terminology (hyaline fibromatosis syndrome) and a modified
      grading system are also included.

PMID- 22383262
TI  - Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography
      coupled with tandem mass spectrometry applicable to routine therapeutic drug
      monitoring.
AB  - The purpose of this study was to develop an ultra-performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics
      for routine therapeutic monitoring. The antiepileptics used in the analyses were
      carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam,
      clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin,
      lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital,
      phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and
      zonisamide. After protein precipitation of 50 MUL plasma with methanol, the
      supernatant was diluted with water or was evaporated to dryness and reconstituted
      with mobile phase in the case of benzodiazepines. Separation was achieved on an
      Acquity UPLC BEH C18 column with a gradient mobile phase of 10 mm ammonium
      acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An
      Acquity TQD instrument in multiple reaction monitoring mode with ion mode
      switching was used for detection. All antiepileptics were detected and quantified
      within 10 min, with no endogenous interference. All the calibration curves showed
      good linearity in the therapeutic range (r2  < 0.99). The precision and accuracy
      values for intra- and inter-assays were within +/-15% except for phenobarbital
      and tiagabine. A good correlation was observed between the concentration of
      clinical samples measured by the new method described here and the conventional
      methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than
      those detected by the immunoassays, which might be caused by the cross-reaction
      of antibodies with their metabolites. In conclusion, we developed a simple and
      selective UPLC-MS/MS method suitable for routine therapeutic monitoring of
      antiepileptics.

PMID- 22383263
TI  - Anticancer activity of silver-N-heterocyclic carbene complexes: caspase
      independent induction of apoptosis via mitochondrial apoptosis-inducing factor
      (AIF).
AB  - Fourteen silver(I) complexes bearing N-heterocyclic carbene (NHC) ligands were
      prepared and evaluated for anticancer activity. Some of these were found to
      exhibit potent antiproliferative activity toward several types of human cancer
      cell lines, including drug-resistant cell lines, with IC(50) values in the
      nanomolar range. An initial investigation into the mechanism of cell death
      induced by this family of silver(I) complexes was carried out. Cell death was
      shown to result from the activation of apoptosis without involvement of primary
      necrosis. In HL60 cells, silver-NHCs induce depolarization of the mitochondrial
      membrane potential (DeltaPsi(m)) and likely allow the release of mitochondrial
      proteins to elicit early apoptosis. This effect is not related to the
      overproduction of reactive oxygen species (ROS). In addition, apoptosis is not
      associated with the activation of caspase-3, but is triggered by the
      translocation of apoptosis-inducing factor (AIF) and caspase-12 from mitochondria
      and the endoplasmic reticulum, respectively, into the nucleus to promote DNA
      fragmentation and ultimately cell death. No modification in cell-cycle
      distribution was observed, indicating that silver-NHCs are not genotoxic.
      Finally, the use of a fluorescent complex showed that silver-NHCs target
      mitochondria. Altogether, these results demonstrate that silver-NHCs induce
      cancer cell death independent of the caspase cascade via the mitochondrial AIF
      pathway.

PMID- 22383264
TI  - New insights into sulfur deposition on gold using dithiobisphthalimide as a new
      precursor.
AB  - Dithiobisphthalimide is used as a new precursor for the spontaneous deposition of
      sulfur on gold surfaces in acetonitrile. Characterization of the modified
      surfaces is achieved using X-ray photoelectron spectroscopy (XPS),
      electrochemistry and scanning tunneling microscopy (STM). The reported results
      indicate that the sulfur deposition is an efficient and fast process and that
      high coverages can be reached very quickly. Sequential high-resolution STM in air
      allows the direct observation, for the first time, of the mobility of the usually
      observed rectangular structures as individual units. It also shows the reversible
      association/dissociation of these rectangles. The nature of these structures is
      highly debated in the literature and the present work provides new insights into
      their nature through the use of a new sulfur precursor under non-traditional
      conditions. To explain our results we consider these structures as simple sulfur
      adlayers on the gold surface.

PMID- 22383265
TI  - Depression in lung cancer patients: the role of perceived stigma.
AB  - OBJECTIVE: Previous research has shown that lung cancer patients are at an
      increased risk for depressive symptomatology; however, little is known about the
      factors contributing to depression in these patients. This study focused on the
      possible association between perceived stigma related to a lung cancer diagnosis
      and depressive symptomatology. It was hypothesized that greater perceived stigma
      would be related to greater depressive symptomatology and that perceived stigma
      would account for variance in depressive symptomatology above and beyond that
      accounted for by relevant clinical, demographic, and psychosocial variables.
      METHOD: A sample of 95 participants receiving chemotherapy for stage II-IV non
      small cell lung cancer was recruited during routine outpatient chemotherapy
      visits. Participants completed a demographic questionnaire and self-report
      measures assessing perceived stigma, depressive symptomatology, and other
      psychosocial variables. A medical chart review was conducted to assess clinical
      factors. RESULTS: As hypothesized, there was a positive association between
      perceived stigma and depressive symptomatology, r = 0.46, p<0.001. Perceived
      stigma also accounted for significant unique variance in depressive
      symptomatology above and beyond that accounted for by relevant demographic,
      clinical, and psychosocial factors, beta = 0.19, p<0.05. CONCLUSIONS: Future
      research should aim to replicate and extend these findings in longitudinal
      studies and explore whether lung cancer patients' depressive symptomatology can
      be ameliorated by targeting perceived stigma.

PMID- 22383266
TI  - Inhalation aromatherapy in children and adolescents undergoing stem cell
      infusion: results of a placebo-controlled double-blind trial.
AB  - OBJECTIVE: Though often lifesaving, stem cell transplantation (SCT) is a period
      of great distress for both child and parent. METHODS: We conducted a double
      blind, placebo-controlled randomized study evaluating the effect of the
      respiratory administration of bergamot essential oil on the anxiety, nausea, and
      pain of 37 pediatric patients with malignant and non-malignant disorders
      undergoing stem cell infusion and their parents. Patients were assessed at the
      time of recruitment, prior to infusion, upon infusion completion, and one hour
      post-infusion using the Spielberger State-Trait Anxiety Inventory (STAI) for
      parents and the STAIC, Children's Behavioral Style Scale (CBSS), visual analogue
      scale (VAS) for pain and nausea, and the Emotionality Activity Sociability and
      Impulsivity instrument (EASI) for children. RESULTS: Children and adolescents in
      the treatment group experienced greater anxiety (p = 0.05) and nausea (p = 0.03)
      one hour post-infusion. Reported pain in both groups was no longer significant
      one hour post-infusion. Parental anxiety declined in both groups but did not
      reach statistical significance. Child's monitoring coping style was significantly
      predictive of transitory anxiety post-infusion (p = 0.01). CONCLUSIONS: Although
      this trial did not report a benefit of inhalation aromatherapy for reducing
      anxiety, nausea, or pain when added to standard supportive care, it provides the
      first experimental rather than descriptive report on testing a single therapeutic
      essential oil among children and adolescents undergoing stem cell infusion.
      Future research may consider exploring the cutaneous application of essential oil
      through massage or other psychoeducational counseling interventions among parents
      with elevated anxiety and patients with greater information seeking coping styles
      during SCT.

PMID- 22383267
TI  - Does psychological adjustment of melanoma survivors differs between genders?
AB  - OBJECTIVE: Survival rates of cancer have significantly increased. However, cancer
      survivors face physical, psychological and social difficulties, while adjusting
      to post-illness status. We examined between-gender differences in the
      psychological adjustment (mental well-being, distress and subjective level of
      functioning), the putative origin of those differences, and the roles of
      cognitive appraisal, hardiness and attachment style in the psychological
      adjustment of melanoma survivors.   METHODS: Our sample included 300 malignant
      melanoma survivors (182 women and 118 men). Most were diagnosed in stages IA and
      IB of the disease, and had no evidence of disease for 5 years or more.
      Participants completed self-report questionnaires regarding personal data,
      adjustment measured by sense of well-being, distress and subjective functioning,
      cognitive appraisal (primary and secondary) and personal resources (hardiness and
      attachment style).   RESULTS: Between-gender differences were revealed in
      psychological adjustment and in various components of cognitive appraisal and
      attachment styles. Women revealed more distress, less secondary cognitive
      appraisal and were more secure in attachment styles. Men showed higher secondary
      appraisal and were more dismissing-avoidant in attachment. No between-group
      differences were found in mental well-being, subjective functioning, and primary
      cognitive appraisal or in the global measure of hardiness.   CONCLUSIONS: We
      present social processes that seem to account for gender differences in behavior
      and response to stress, and psychological explanations for these findings. This
      study contributes to the field of psycho-oncology by identifying factors that
      promote adjustment among melanoma survivors.

PMID- 22383268
TI  - Mindfulness-based cognitive therapy reduces chronic cancer-related fatigue: a
      treatment study.
AB  - INTRODUCTION: About one-third of cancer survivors suffer from severe chronic
      fatigue. Aim of this study was to evaluate the efficacy of mindfulness-based
      cognitive group therapy in reducing severe chronic fatigue in cancer survivors
      with mixed diagnoses. PATIENTS AND METHODS: Participants (n = 100) were randomly
      selected from a cohort and allocated to an intervention and a waiting list
      condition. Analyses were based on 59 participants in the intervention condition
      and 24 in the waiting-list condition. Fatigue severity (Checklist Individual
      Strength), functional impairment (Sickness Impact Profile) and well being (Health
      and Disease-Inventory) were assessed before and after the 9-week intervention.
      The intervention group had a follow-up 6 months following the intervention.
      RESULTS: At post-treatment measurement the proportion of clinically improved
      participants was 30%, versus 4% in the waiting list condition (chi(2) (1) = 6.71;
      p = 0.007). The mean fatigue score at post-measurement was significantly lower in
      the intervention group than in the waiting list group corrected for pre-treatment
      level of fatigue. The mean well-being score at post-measurement was significantly
      higher in the intervention group than in the waiting list group corrected for pre
      treatment level of well-being. The treatment effect was maintained at 6-month
      follow-up. No difference between the two conditions was found in functional
      impairment. DISCUSSION: Mindfulness-based cognitive therapy is an effective
      treatment for chronic cancer-related fatigue.

PMID- 22383269
TI  - Quality of life of family caregivers 5 years after a relative's cancer diagnosis:
      follow-up of the national quality of life survey for caregivers.
AB  - BACKGROUND: Although cancer has been considered as a chronic disease for those
      diagnosed, the long-term impact of cancer on the family caregivers' quality of
      life (QOL) remains unknown. Thus, the current study aimed: (a) to characterize
      family caregivers of cancer survivors, (b) to describe the multidimensional
      aspects of QOL of family caregivers of cancer survivors, and (c) to identify
      demographic and caregiving experience factors that may play significant roles in
      the caregivers' QOL around 5 years after the relative's initial diagnosis.
      Methods. A total of 1218 caregivers participated in the 5-year follow-up
      nationwide QOL Survey for Caregivers. Demographics and caregiving experiences
      were measured 2 years post-diagnosis of their relative's cancer. Multidimensional
      aspects of QOL were assessed, including mental and physical health, psychological
      adjustment, and spirituality at 5 years post-diagnosis. RESULTS: Three groups of
      caregivers were identified: former caregivers due to the recipients being in
      remission, former caregivers whose recipients were deceased, and current
      caregivers. Current caregivers reported worst levels of QOL. Bereaved caregivers
      reported lower levels of psychological and spiritual adjustment than former
      caregivers whose recipients were in remission. In addition, caregivers' age and
      stress were consistent predictors of QOL across three caregiver groups at 5 years
      post-diagnosis. CONCLUSIONS: The findings help to increase evidence-based
      awareness of the long-term impact of cancer on the family caregivers' QOL.
      Findings also have implications for developing programs, whereby family
      caregivers in the various phases of caregivership will benefit by improving their
      QOL.

PMID- 22383270
TI  - Determinants of the burden and positivity of family caregivers of terminally ill
      cancer patients in Korea.
AB  - OBJECTIVE: Caregivers may experience positive or negative feelings about their
      role. The study investigated the determinants of the burden and positivity of
      family caregivers of Korean terminal cancer patients. METHODS: A multicenter
      cross-sectional survey was conducted with 139 family caregivers. Determinants of
      caregiver's burden and positivity were assessed by the Caregiver Reaction
      Assessment Scale and by three questions based on a previous study, respectively.
      Two separate hierarchical multiple regression models were used. RESULTS: Each
      domain of the caregiver's burden and positivity was explained by different
      factors, with the total explained variance ranging between 14.4-33.6% and 2.6
      18.3%, respectively. Caregivers who were unmarried, less educated, and/or had low
      incomes were more likely to be negatively affected, while those who shared
      caregiving responsibilities were less prone to negative consequences. Caregivers
      who were male, religious practitioners, and who perceived a higher burden of
      schedule disruptions were more likely to have a positive perception of their
      role, while those who perceived a lack of family support were less likely.
      CONCLUSIONS: Our results highlight the importance of sharing the caregiving
      burden with the other family members. Organizing a family meeting can provide an
      opportunity for other family members to acknowledge the feelings and reactions of
      the primary caregivers, and can prompt the sharing of caregiving
      responsibilities.

PMID- 22383271
TI  - Dysplasia severity, but not experiences during colposcopy, predicts adherence to
      follow-up colposcopy.
AB  - OBJECTIVE: Patient adherence with treatment recommendations is an essential
      factor for the effectiveness of cervical cancer screening programs. Psychological
      factors may play a role in patient adherence to cervical cancer screening. The
      present study aimed to extend knowledge of women's adherence to follow-up
      colposcopy, by examining possible predictive biopsychosocial variables measured
      at colposcopy and objective attendance rates from patients' medical files.
      METHODS: Baseline data on psychosocial factors (e.g. demographic variables, state
      anxiety, and pain) were collected from 141 women prior to undergoing colposcopy
      for the first time (M age = 29.63, SD = 8.39). Experiences of colposcopy and
      adherence to follow-up (within two years) were assessed subsequently. RESULTS:
      There were no associations between adherence and demographic variables. Women
      with severe dysplasia were more likely to adhere to follow-up colposcopy than
      women with other histology grades. Women who did not attend for follow-up
      reported significantly greater state anxiety and pain unpleasantness following
      colposcopy than women who did attend. A multivariate logistic regression analysis
      revealed that the psychological experiences of colposcopy did not predict
      adherence status. However, dysplasia severity made a significant contribution to
      the model. The odds of adhering to colposcopy for patients with severe dysplasia
      were 3.57 times higher than for patients with normal histology, and 4.35 times
      higher than for patients with moderate dysplasia (p = 0.005). CONCLUSIONS:
      Colposcopy-related experiences do not appear to be strong predictors of
      adherence, but women with dysplasia grades other than 'severe' should be targeted
      for follow-up recommendations and advice.

PMID- 22383272
TI  - Cancer Treatment Survey (CaTS): development and validation of a new instrument to
      measure patients' preparation for chemotherapy and radiotherapy.
AB  - OBJECTIVE: Cancer patients experience high levels of pre-treatment anxiety.
      Chemotherapy and radiotherapy are threatening medical procedures. Preparation for
      these procedures should include the provision of sensory and procedural
      information, and addressing fears. The aim of this study was to develop a cancer
      treatment survey (CaTS) to assess the preparation for chemotherapy and
      radiotherapy in cancer patients. METHODS: Drawing on evidence for how to prepare
      patients for threatening procedures, items were generated by
      psychosocial/clinical experts and pilot tested with cancer patients. The 36-item
      draft CaTS was administered to 192 cancer patients commencing chemotherapy for
      lymphoma, breast or colon cancer. Participants also completed the Hospital
      Anxiety and Depression Scale (HADS) and basic medical and demographic information
      was recorded. RESULTS: A systematic process of item selection removed 11 items.
      Factor analysis indicated a two-factor solution, with 11 items representing
      sensory/psychological concerns and 14 items representing procedural concerns. The
      two subscales demonstrated excellent internal reliability with Cronbach's alpha
      both over 0.90 and the average inter-item correlation for each scale exceeded
      0.30. Divergent validity was established for both CaTS subscales with the HADS-A
      and-T (all r<0.30). Younger participants (under 65 years of age) had
      significantly greater procedural concerns (p = 0.001; medium effect).
      CONCLUSIONS: The CaTS is a two factor, 25-item measure that assesses
      sensory/psychological concerns and procedural concerns relating to cancer
      treatment. The instrument provides a reliable and valid outcome measure for
      interventions to prepare cancer patients for chemotherapy and radiotherapy.

PMID- 22383273
TI  - Using the theory of planned behavior to understand health professionals'
      attitudes and intentions to refer cancer patients for psychosocial support.
AB  - OBJECTIVE: To describe oncology professionals' patterns of referral to existing
      community and psychosocial support services, including complementary therapies
      utilizing the theory of planned behavior (TPB). METHODS: An exploratory cross
      sectional survey of 72 oncology professionals including nurses (73.6%), medical
      practitioners (19.4%) and allied health professionals (6.9%) from health
      institutions in South Australia assessed past referral patterns, perceived
      attitudes of peers, control over and attitudes toward, referral, past referral
      practices and how these impact on intention to refer. RESULTS: Referral to
      support services such as a cancer helpline, allied health or complementary
      services was infrequent. A hierarchical regression entering awareness, past
      referral and the TPB variables (attitude, subjective norm and perceived control)
      explained 51% of the variance on the outcome 'intention to refer'. Barriers to
      referral for support included lack of local services for remote patients, and
      financial considerations. CONCLUSION: Interventions with health professionals
      should focus on the development of a culture, which recognizes the importance of
      addressing a breadth of patient needs across the cancer trajectory. Education and
      support for health professionals is required to ensure that they feel comfortable
      discussing support needs and referring to appropriate support services.

PMID- 22383274
TI  - Israeli and Chinese partners of women with breast cancer: a cross-cultural view
      of marital issues.
AB  - OBJECTIVE: Cultural nuances may influence the interface between the cancer
      experience and marital issues, specifically for the partner. Most of the
      literature has focused on the woman's narrative or couple's adjustment to cancer
      in general. The purpose of this study was to describe and compare the marital
      relationship, sexuality, and marital adjustment of Israeli and Chinese husbands
      of women with breast cancer and the discussion of the health-care team concerning
      these issues. METHODS: A convenience sample of 50 Chinese and 50 Israeli men,
      ages of 28-79 years, completed components of the Psychological Adjustment to
      Illness Scale, the Locke Wallace Adjustment Scale, and a background
      questionnaire. RESULTS: The majority of husbands were in their first marriage.
      The average time since diagnosis was 16.7 months. No significant difference was
      found between the two groups on issues of marital relationship. Significant
      differences were found between Israeli and Chinese husbands on sexual interest,
      pleasure, and performance (p<0.05). Israeli husbands reported a significantly
      higher level of marital adjustment as opposed to the Chinese husbands (p =
      0.006). Marital adjustment for both groups was significantly related only to
      perceived quality of the relationship (p<0.03). CONCLUSIONS: Significant cultural
      differences were found in sexuality variables with no differences discerned on
      marital relationship variables. Couple-based interventions for marital issues are
      a critical component of support for both partners. Culturally sensitive
      assessment and care of the spouse as well as the woman with breast cancer should
      be part of a holistic, comprehensive family care plan.

PMID- 22383275
TI  - The mobile phone as a tool in improving cancer care in Nigeria.
AB  - OBJECTIVE: The use of mobile phone as a tool for improving cancer care in a low
      resource setting. METHODS: A total of 1176 oncology patients participated in the
      study. Majority had breast cancer. 58.4% of the patients had no formal education;
      10.7 and 9.5% of patients had college or graduate education respectively. Two out
      of every three patients lived greater than 200 km from hospital or clinic. One
      half of patients rented a phone to call. RESULTS: At 24 months, 97.6% (1132
      patients) had sustained their follow-up appointments as against 19.2% (42
      patients) who did not receive the phone intervention. 72.8% (14 102 calls) were
      to discuss illness/treatment. 14% of the calls were rated as emergency by the
      oncologist. 86.2% of patients found the use of mobile phone
      convenient/excellent/cheap. 97.6% found the use of the phone worthwhile and
      preferred the phone to traveling long distance to hospital/clinic. Also the
      patients felt that they had not been forgotten by their doctors and were been
      taken care of outside the hospital/clinic. CONCLUSIONS: Low resource countries
      faced with the burden of cancer care, poor patient follow-up and poor
      psychosocial support can cash in on this to overcome the persistent problem of
      poor communication in their healthcare delivery. The potential is enormous to
      enhance the use of mobile phones in novel ways: developing helpline numbers that
      can be called for cancer information from prevention to treatment to palliative
      care. The ability to reach out by mobile phone to a reliable source for medical
      information about cancer is something that the international community, having
      experience with helplines, should undertake with colleagues in Africa, who are
      experimenting with the mobile phone potential.

PMID- 22383276
TI  - The ST Pinch: A side chain-to-side chain hydrogen-bonded motif.
AB  - The ST Pinch is a 12-membered hydrogen-bonded motif (Ser/Thr-Xaa-Ser/Thr)
      involving the side chain oxygen atoms of two Ser/Thr residues. We identified the
      ST Pinch in 104 proteins in a database containing high-resolution crystal
      structures. Conformational analysis of the ST Pinch in these proteins points to
      specific preferences for the Xaa residue and a high propensity of this residue to
      adopt positive phi angles. Our results suggest that this motif serves as a linker
      of secondary structural elements within proteins and is a new addition to the
      existing list of short hydrogen bond-stabilized motifs in proteins.

PMID- 22383277
TI  - Different mechanisms for nanoparticle formation between pDNA and siRNA using
      polyrotaxane as the polycation.

PMID- 22383279
TI  - Stress management training for breast cancer surgery patients.
AB  - OBJECTIVE: This study evaluated the psychological effects of a pre-surgical
      stress management training (SMT) in cancer patients. METHODS: Stress management
      training comprised four sessions in total: on 5 days and 1 day pre-surgery and on
      2 days and 1 month post-surgery. Patients also received audio CDs with relaxation
      and coping skills exercises. Patients were randomly assigned to the SMT (N = 34)
      or a regular care condition (N = 36). Depression, anxiety, quality of life,
      perception of control, fatigue, pain, sleep problems, and surgery-related somatic
      symptoms were measured at Day 6 and Day 1 pre-surgery, and Day 2, 5, 30 and 90
      post-surgery. RESULTS: Depression and fatigue decreased in the intervention group
      and increased in the control group, leading to significant group differences at
      Day 2 (fatigue) and Day 5 post-surgery (fatigue and depression). It also appeared
      that surgery-related symptoms had increased more in the control group 3 months
      post-surgery than in the SMT group. No intervention effects were observed for
      anxiety, pain, and sleep problems. CONCLUSION: The use of a short psychological
      intervention is effective in reducing depression and fatigue in the post-surgical
      period, although the effects are of short duration.

PMID- 22383280
TI  - The nature of tryptophan radicals involved in the long-range electron transfer of
      lignin peroxidase and lignin peroxidase-like systems: Insights from quantum
      mechanical/molecular mechanics simulations.
AB  - A catalytically active tryptophan radical has been demonstrated to be involved in
      the long-range electron transfer to the heme cofactor of lignin peroxidase (LiP)
      from Phanerochaete chrysosporium although no direct detection by EPR spectroscopy
      of the tryptophan radical intermediate has been reported to date. An engineering
      based approach has been used to manipulate the microenvironment of the redox
      active tryptophan site in LiP and Coprinus cinereus Peroxidase (CiP), allowing
      the direct evidence of the tryptophan radical species. In light of the newly
      available EPR experimental data, we performed a quantum mechanical/molecular
      mechanics computational study to characterize the tryptophan radicals in the
      above protein matrices as well as in pristine LiP. The nature of the tryptophan
      radicals is discussed together with the analysis of their environment with the
      aim of understanding the different behavior of pristine LiP in comparison with
      that of LiP and CiP variants.

PMID- 22383281
TI  - [Telaprevir-benefit assessment of the Institute for Quality and Efficiency in
      Health Care (IQWiG) in accordance with S 35a SGB V (dosing evaluation)].

PMID- 22383282
TI  - Barrett's Adenocarcinomas are frequently underdiagnosed as "high grade
      intraepithelial neoplasia".
AB  - BACKGROUND: Relevant guidelines require that a primary histological diagnosis of
      high-grade intraepithelial neoplasia (HGIEN) in Barrett's oesophagus, be
      submitted to a second opinion by an expert gastroenterological pathologist. To
      date, however, no pertinent study of the outcome of such second-opinion diagnoses
      has been published. PATIENTS AND METHODS: Between 2001 and 2005, histological
      slides from 275 patients with the primary diagnosis HGIEN underwent a second
      opinion review. The resulting diagnoses were checked by follow-up in 207 of these
      patients (75.3 %). RESULTS: The second-opinion diagnosis no IEN (n = 27) was
      confirmed in 85.2 % of the cases, 7.4 % had LGIEN, 3.7 % had HGIEN or a well
      differentiated Barrett's adenocarcinoma (BCA) (1 patient, each). In the single
      patient with the second-opinion diagnosis LGIEN, endoscopic resection revealed a
      well-differentiated BCA, Follow-up examinations confirmed the second-opinion
      diagnosis BCA in 5 out of 12 patients, in 1 patient no IEN was found, and 6
      patients had a BCA. The second-opinion diagnosis BCA was confirmed by follow-up
      examinations in 145 patients (86.8 %), in 12 patients (7.2 %) follow-up revealed
      HGIEN and in 10 no neoplasia. CONCLUSION: The results of this study show that the
      demand for a second opinion from an expert gastroenterological pathologist is
      justified, and also that BCA is frequently underdiagnosed as HGIEN.

PMID- 22383283
TI  - Cap-assisted colonoscopy (CAC) significantly extends visualization in the right
      colon.
AB  - BACKGROUND: Although colonoscopy is the standard procedure in the diagnosis of
      colorectal neoplasia, a significant number of clinically relevant lesions may be
      missed even by experienced endoscopists using current technology. Particular
      problems may occur with blind spots behind the semilunar folds and within the
      right colon. A transparent cap mounted at the tip of a colonoscope may be an easy
      way to extend the visual field during colonoscopy and may improve the detection
      rate of mucosal lesions. However, data in the literature are controversial and
      the quantity of the potential extension of visualization by a transparent cap has
      not been reported yet. MATERIAL AND METHODS: The significance of cap-assisted
      colonoscopy (CAC) to increase visualization within different colonic segments
      (rectum, sigmoid colon, descending colon, transverse colon, ascending colon,
      cecum) was quantitatively analyzed by randomized back-to-back colonoscopies with
      and without cap. The investigations were performed in a colonic training model by
      5 investigators. The inner colonic surface was stained by a raster of dots and
      the number of dots counted during colonoscopy served as a measure for the visible
      surface area of each segment. RESULTS: The time to advance the colonoscope to the
      respective colonic segments and the overall time to reach the cecum were not
      significantly different between conventional and CAC. In contrast, overall
      withdrawal time and withdrawal times for the cecum, ascending colon, descending
      colon and rectum were significantly longer for CAC, but not for the transverse
      and sigmoid colon. Visualization of the colonic surface was significantly
      increased during CAC. Overall, 59.76 +/- 2.70 % of the maximal countable dots
      were visualized without cap and 85.36 +/- 9.62 % with cap. The improvement of
      visualization was only significant for the right colon, but not for the rectum,
      sigmoid or descending colon. CONCLUSION: The finding of the present study
      suggests that the extension of visualization by CAC may be of particular value
      for the right colon.

PMID- 22383284
TI  - Gallbladder hemorrhage mimicking acute cholecystitis in a patient under
      antiplatelet therapy.
AB  - Hemorrhage within the gallbladder is rare but potentially fatal. It can be easily
      overlooked and misdiagnosed because of its low incidence and presentation that is
      similar to other types of hepatobiliary disease. We present an unusual case of
      gallbladder hemorrhage in a 36-year-old male patient who was taking antiplatelet
      medication following cardiac surgery. The patient was misdiagnosed with acute
      primary cholecystitis and, in consideration of postoperative complications with
      cardiovascular comorbities, serial treatment with urgent percutaneous
      transhepatic gallbladder drainage and delayed laparoscopic cholecystectomy was
      prescribed. Unexpectedly, a gallbladder hemorrhage was intraoperatively confirmed
      as the gallbladder appeared filled with dark blood clot-like materials. The
      patient recovered well and was discharged on the 3rd postoperative day without
      complications. In patients who are on antiplatelet therapy, gallbladder
      hemorrhage should be considered in the differential diagnosis if they have
      symptoms typical of biliary colic. In addition, delayed surgery with prompt
      biliary diversion may represent a safe and effective treatment approach.

PMID- 22383285
TI  - [Tuberculosis as a rare cause for an abdominal mass: report on three cases and
      review of the literature].
AB  - Here we present 3 patients with abdominal pain, weight loss and fever in
      combination with abdominal tumours which were all attributable to an ongoing
      mycobacterial infection. Worldwide, but especially in developing countries,
      tuberculosis is still an important cause of morbidity and death. In
      industrialised countries, however, tuberculosis is rarely considered as a
      differential diagnosis, especially when the primary lesion is not localised in
      the lung. Primary abdominal manifestations, in particular, are a frequent cause
      of delayed diagnosis due to the often elaborated necessary diagnostics. Once the
      diagnosis has been established, a combination therapy starting with isoniazid,
      rifampicin, pyrazinamide and ethambutol, i. e., the standard therapeutic regimen
      for pulmonary tuberculosis, is recommended. Concomitant diseases and atypical
      courses, however, often constitute serious challenges to the treating physician.
      Therefore, we here give a review of the literature and discuss three cases of
      abdominal tuberculosis with regard to clinical characteristics, diagnostic
      pitfalls and courses of disease.

PMID- 22383286
TI  - [Sonography today: reference values in abdominal ultrasound: aorta, inferior vena
      cava, kidneys].
AB  - OBJECTIVE: Reference values for B-mode abdominal ultrasound are controversially
      discussed due to the limited data in the literature. A systematic survey of data
      published so far is presented for the big retroperitoneal vessels and the
      kidneys. METHODS: A literature review of reference values in the abdomen from
      1970 to 2011 in healthy subjects 18 years of age and older was undertaken.
      According to the determination of reference intervals for laboratory values,
      reference values are generally determined using 95 % reference intervals and
      their associated 90 % confidence intervals. The diameters of the abdominal aorta
      and the inferior vena cava were evaluated as well as the length, width,
      thickness, parenchymal thickness and volume of the kidneys. RESULTS: 61 studies
      were analysed. Reference values determined for the aorta vary considerably
      according to age and gender of the probands, measuring position and measuring
      technique. The upper interval limits of the 95 % reference intervals lie between
      17 and 40 mm. The diameter of the inferior vena cava depends on the position of
      the patient, the measuring site, respiration and the resting heart rate. Normal
      results up to 27 mm can be encountered. Influencing factors on the size and
      volume of the kidneys are the side (right/left), age, gender, anthropometric
      parameters and the ethnic membership of the probands. For central European women,
      9 cm - 12.8 cm can be regarded as the normal range of the length of the kidney
      and for men 9.2 cm - 13.3 cm. For the width of the kidney, interval limits were
      determined between 3 cm and 7.1 cm, for the thickness between 2.9 cm and 6 cm,
      for the parenchymal thickness between 1.1 cm and 2.3 cm and for the volume
      between 59 and 230 mL. DISCUSSION: Normal values are helpful in delimiting
      numerous pathological changes in the respective organs.

PMID- 22383287
TI  - [Current management of toxic megacolon].
AB  - Toxic megacolon is a rare and life-threatening complication of severe colitis,
      defined as a dilatation of the colon > 6 cm in the absence of distal obstruction
      in combination with signs of systemic toxicity (major criteria: fever,
      tachycardia, leukocytosis, anaemia). Various triggers are known and the most
      common causes are underlying ulcerative colitis and Clostridium difficile.
      Diagnosis can easily be made by clinical examination, routine laboratory
      parameters and a plain X-ray of the abdomen. Much more difficult is to decide
      between non-surgical treatment including intensive care treatment or surgery
      (mostly subtotal colectomy with terminal ileostomy). Non-surgical therapy
      includes balancing of electrolytes and fluid volumes, broad-spectrum antibiotics
      including metronidazole, positioning of patients and probably careful
      intermittent decompression. In case of ulcerative colitis immunosuppression
      should be started with corticosteroids and potentially with calcineurin
      inhibitors. In pseudomembranous colitis vancomycin should be given orally and
      metronidazole should be given intravenously. As far as possible the patient
      should be treated in a centre with experience in the field.

PMID- 22383288
TI  - [Procain Infusion in Pain Treatment of Acute Pancreatitis: yes or no, that is the
      Question].

PMID- 22383289
TI  - [State of NOTES development in Germany: Status report of the D-NOTES-Congress
      2011th].

PMID- 22383290
TI  - Discovery of N-arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide
      derivatives as HCV NS5B polymerase inhibitors.
AB  - The metal ion chelating beta-N-hydroxy-gamma-ketocarboxamide pharmacophore was
      integrated into a quinazolinone scaffold, leading to N-arylalkyl-3-hydroxy-4-oxo
      3,4-dihydroquinazolin-2-carboxamide derivatives as hepatitis C virus (HCV) NS5B
      polymerase inhibitors. Lead optimization led to the identification of N
      phenylpropyl carboxamide 9 k (IC(50) =8.8 MUM). Compound 9 k possesses
      selectivity toward HCV1b replicon Ava.5 cells (EC(50) =17.5 MUM) over parent Huh
      7 cells (CC(50) =187.5 MUM). Compound 9 k effects a mixed mode of NS5B
      inhibition, with NTP-competitive displacement properties. The interaction between
      9 k and NS5B is stabilized by the presence of magnesium ions. Docking studies
      showed that the binding orientation of 9 k occupies the central portions of both
      magnesium-mediated and NTP-ribose-response binding sites within the active site
      region of NS5B. As a result, 3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide
      derivatives are disclosed herein as novel, mainly active site inhibitors of HCV
      NS5B polymerase.

PMID- 22383291
TI  - Nickel-catalyzed Heck-type alkenylation of secondary and tertiary alpha-carbonyl
      alkyl bromides.

PMID- 22383292
TI  - Combining MFD and PIE for accurate single-pair Forster resonance energy transfer
      measurements.
AB  - Single-pair Forster resonance energy transfer (spFRET) experiments using single
      molecule burst analysis on a confocal microscope are an ideal tool to measure
      inter- and intramolecular distances and dynamics on the nanoscale. Different
      techniques have been developed to maximize the amount of information available in
      spFRET burst analysis experiments. Multiparameter fluorescence detection (MFD) is
      used to monitor a variety of fluorescence parameters simultaneously and pulsed
      interleaved excitation (PIE) employs direct excitation of the acceptor to probe
      its presence and photoactivity. To calculate accurate FRET efficiencies from
      spFRET experiments with MFD or PIE, several calibration measurements are usually
      required. Herein, we demonstrate that by combining MFD with PIE information
      regarding all calibration factors as well as an accurate determination of spFRET
      histograms can be performed in a single measurement. In addition, the quality of
      overlap of the different detection volumes as well as the detection of acceptor
      photophysics can be investigated with MFD-PIE. Bursts containing acceptor
      photobleaching can be identified and excluded from further investigation while
      bursts that contain FRET dynamics are unaffected by this analysis. We have
      employed MFD-PIE to accurately analyze the effects of nucleotides and substrate
      on the interdomain separation in DnaK, the major bacterial heat shock protein 70
      (Hsp70). The interdomain distance increases from 47 A in the ATP-bound state to
      84 A in the ADP-bound state and slightly contracts to 77 A when a substrate is
      bound. This is in contrast to what was observed for the mitochondrial member of
      the Hsp70s, Ssc1, supporting the notion of evolutionary specialization of Hsp70s
      for different cellular functions in different organisms and cell organelles.

PMID- 22383293
TI  - Congenital heart disease and the liver.
AB  - There are approximately 1 million adult patients with congenital heart disease
      (CHD) in the United States, and the number is increasing. Hepatic complications
      are common and may occur secondary to persistent chronic passive venous
      congestion or decreased cardiac output resulting from the underlying cardiac
      disease or as a result of palliative cardiac surgery; transfusion or drug-related
      hepatitis may also occur. The unique physiology of Fontan circulation is
      particularly prone to the development of hepatic complications and is, in part,
      related to the duration of the Fontan procedure. Liver biochemical test
      abnormalities may be related to cardiac failure, resulting from intrinsic liver
      disease, secondary to palliative interventions, or drug related. Complications of
      portal hypertension and, rarely, hepatocellular carcinoma (HCC) may also occur.
      Abnormalities such as hypervascular nodules are often observed; in the presence
      of cirrhosis, surveillance for HCC is necessary. Judicious perioperative support
      is required when cardiac surgery is performed in patients with advanced hepatic
      disease. Traditional models for liver disease staging may not fully capture the
      severity of disease in patients with CHD. The effectiveness or safety of isolated
      liver transplantation in patients with significant CHD is limited in adults;
      combined heart-liver transplantation may be required in those with decompensated
      liver disease or HCC, but experience is limited in the presence of significant
      CHD. The long-term sequelae of many reparative cardiac surgical procedures are
      not yet fully realized; understanding the unique and diverse hepatic associations
      and the role for early cardiac transplantation in this population is critical.
      Because this population continues to grow and age, consideration should be given
      to developing consensus guidelines for a multidisciplinary approach to optimize
      management of this vulnerable population.

PMID- 22383294
TI  - Apoptosis index correlates with chemotherapy efficacy and predicts the survival
      of patients with gastric cancer.
AB  - The objectives of this study are to investigate the apoptotic changes in gastric
      adenocarcinoma following neoadjuvant chemotherapy and to illuminate its
      correlation with response. One 67 gastric cancer patients with cT2-4 or TanyN1
      3M0 between January 2006 and December 2007 were included. All patients had
      previous gastrectomy and D2 lymphadenectomy with curative intent performed. A
      total of 12 cycles of preoperative mFOLFOX7 chemotherapy was recommended for all
      patients, and 83 patients received only adjuvant chemotherapy. Resected specimens
      were subjected to in situ TUNEL assay and scanned with Applied Imaging Ariol SL
      50. Apoptosis index (AI) was significantly higher in the patient received
      preoperative chemotherapy (CS group) than in the patient did not (S group). In
      the CS group, AI was found to have a strong positive correlation with the
      pathological response (rho = 0.403, P = 0.0002). A ROC curve presented a score of
      49.4 as the AI cutoff value for response, dividing the CS group into two
      subgroups with significantly different prognoses (P = 0.003) and further allowing
      identification of 8 patients with significantly better prognosis out of 48
      patients evaluated as grades 1a-b according to a pathological response evaluation
      (P = 0.022). In conclusion, AI is correlated with efficacy of preoperative
      chemotherapy and prognosis of gastric cancer patients following neoadjuvant
      chemotherapy. An AI cutoff value for response may be used as a complementary
      approach to current pathological response evaluations to help identify potential
      responders.

PMID- 22383295
TI  - Impact of expression system on the function of the C6.5 diabody PET radiotracer.
AB  - The ability of engineered antibodies to rapidly and selectively target tumors
      that express their target antigen makes them well suited for use as radioimaging
      tracers. The combination of molecular size and bivalent nature makes diabody
      molecules a particularly promising structure for use as radiotracers for
      diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5
      diabody (C6.5db) is an effective radiotracer in preclinical models of HER2
      positive cancer. The aim of this study was to evaluate the impact on radiotracer
      performance, associated with expressing the C6.5db in the Pichia pastoris (P
      C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P
      C6.5db led to faster blood clearance and lower overall tumor uptake than seen
      with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background
      ratios that are critical for effective imaging. Dosimetry measurements determined
      in this study for both (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are
      equivalent to other radiotracers currently being administered to patients.

PMID- 22383296
TI  - Suppression of DNA damage in human peripheral blood lymphocytes by a juice
      concentrate: a randomized, double-blind, placebo-controlled trial.
AB  - Chronic inflammation contributes to many prevalent diseases worldwide, and it is
      widely accepted that inflammatory molecules contribute to DNA damage. In this
      ancillary study, we investigated the influence of an encapsulated fruit and
      vegetable juice powder concentrate on peripheral blood lymphocytes (PBL) DNA
      damage. Using a double-blind, placebo-controlled approach, subjects were randomly
      assigned capsules containing placebo, or one of two formulations of the juice
      powder. Blood was drawn at baseline and after 60 days of capsule consumption. We
      found DNA damage in isolated PBL is suppressed after consumption of the
      encapsulated juice powder, and damage was correlated with the level of systemic
      inflammation. These data suggest a potential health benefit by consuming the
      juice concentrate capsules through their ability to suppress DNA damage as
      measured in surrogate tissues (PBL).

PMID- 22383297
TI  - A brief form of interpersonal psychotherapy for adult patients with bulimic
      disorders: a pilot study.
AB  - OBJECTIVE: The aim of the study was to pilot a brief form of interpersonal
      psychotherapy (IPT) for the treatment of patients with bulimic disorders. METHOD:
      Ten patients with bulimic disorder treated with a new brief version of IPT (IPT
      BN10) completed measurements of eating disorders psychopathology (Eating
      Disorders Examination Questionnaire, Bulimic Investigatory Test Edinburgh) and
      depression (Beck Depression Inventory). The results were matched with a group of
      patients treated with conventional IPT and with waiting list control. RESULTS:
      Statistical differences were found between starting and ending of therapy for
      those patients treated with IPT-BN10. Statistical difference was also found when
      comparing with waiting list control. DISCUSSION: The pilot study suggests that
      IPT-BN10 may be an effective treatment for patients having bulimic disorders;
      however, this hypothesis needs to be tested in an experimental way.

PMID- 22383299
TI  - Copper-catalyzed amination of arylboronates with N,N-dialkylhydroxylamines.

PMID- 22383300
TI  - Mass spectrometry detection in comprehensive liquid chromatography: basic
      concepts, instrumental aspects, applications and trends.
AB  - The review, as can be deduced from the title, focuses on both theoretical and
      practical aspects of the use of mass spectrometry as a third, added dimension to
      a comprehensive LC (LC * LC) system, generating the most powerful analytical tool
      today for non-volatile analytes. The first part deals with the technical
      requirements for linkage of an LC * LC system to an MS one, including the choice
      of the mobile phase (buffer and salts), flow rate (splitting), type of ionization
      (interface); advantages and disadvantages of off-line and on-line methods are
      discussed, as well. A discussion of the various aspects of instrumentation is
      provided, both from a chromatographic and mass spectrometry standpoint, with
      particular emphasis directed to the choice of column sets, spatial resolution,
      mass resolving power, mass accuracy, and tandem-MS capabilities. The extent to
      which mass spectrometry may be of aid in unraveling column-outlet multicompound
      bands is highlighted, along with its effectiveness as a chromatographic detector
      of excellent sensitivity, universality yet with potential in terms of selectivity
      and amenability to quantitative analysis over a wide dynamic range. The following
      section of the review contains significant applications of comprehensive two
      dimensional LC coupled to MS in different areas of research, with details on
      interfaces, column stationary phases, modulation and MS parameters. It is not the
      intention of the authors to provide a comprehensive description of the
      techniques, but merely to discuss only those aspects which are essential for
      successful applications of the LC-MS combination. The reader will be acquainted
      with the enormous potential of this hyphenated technique, and the factors and
      instrumental developments that have concurred to make it emerge to a central role
      in specialized fields, such as proteomics.

PMID- 22383301
TI  - X-ray crystal structure of TTHB099, a CRP/FNR superfamily transcriptional
      regulator from Thermus thermophilus HB8, reveals a DNA-binding protein with no
      required allosteric effector molecule.

PMID- 22383302
TI  - Naphthyl and thienyl units as bridges for metal-free dye-sensitized solar cells.
AB  - A series of new organic dyes, comprising a naphthyl moiety as a pi-conjugated
      bridge, different amines as donors, and a cyanoacrylic acid group as an electron
      acceptor and anchoring group, have been designed and synthesized for applications
      in dye-sensitized solar cells (DSSCs). One of the compounds was also
      characterized by single-crystal X-ray structural analysis. All of the dyes
      exhibited maximum absorptions in the range of 371-441 nm. The short-circuit
      photocurrent density, open-circuit voltage, and fill factor (FF) values of the
      devices are in the range of 6.13-10.90 mA cm(-2), 0.62-0.69 V, and 0.62-0.67,
      respectively, corresponding to an overall conversion efficiency of 2.76-4.55%.
      The conversion efficiency reached 38-62% of that of a N719-based device (7.31%)
      fabricated and measured under similar conditions. Steric congestion between the
      naphthyl and aromatic moieties jeopardizes charge transfer from the donor to the
      acceptor. Insertion of an alkenyl entity between the naphthyl entity and the
      aromatic ring alleviates steric congestion and leads to longer wavelength
      electronic absorption spectra.

PMID- 22383303
TI  - Profile of urinary and fecal proanthocyanidin metabolites from common cinnamon
      (Cinnamomum zeylanicum L.) in rats.
AB  - Cinnamon (Cinnamomum zeylanicum L.) bark is widely used as a spice and in
      traditional medicine. Its oligomeric and polymeric proanthocyanidins are believed
      to be partly responsible for the beneficial properties of the plant. We describe
      here the metabolic fate of cinnamon proanthocyanidins in the urine and feces of
      rats fed a suspension of the whole bark. The metabolites include ten mono-, di-,
      and tri- conjugated (epi)catechin phase II metabolites and more than 20 small
      phenolic acids from intestinal microbial fermentation. Some of these are sulfated
      conjugates. Feces contain intact (epi)catechin and dimers. This suggests that
      free radical scavenging species are in contact with the intestinal walls for
      hours after ingestion of cinnamon. The phenolic metabolite profile of cinnamon
      bark in urine is consistent with a mixture of proanthocyanidins that are
      depolymerized into their constitutive (epi)catechin units as well as cleaved into
      smaller phenolic acids during their transit along the intestinal tract, with
      subsequent absorption and conjugation into bioavailable metabolites.

PMID- 22383304
TI  - Integration of organic fluorophores in the surface of polymer-coated colloidal
      nanoparticles for sensing the local polarity of the environment.
AB  - Inorganic hydrophobically capped NPs such as quantum dots, superparamagnetic iron
      oxide, or gold nanoparticles can be modified to make them water-soluble by their
      embedding in an amphiphilic polymer shell. This polymer shell can be
      prefunctionalized by the integration of organic fluorophores, which allows the
      observation of the nanoparticles with fluorescence based techniques. The
      fluorophore could be either located more in the hydrophobic part of the inner
      polymer shell, or on the hydrophilic surface pointing towards solution. Herein we
      prepared gold nanoparticles decorated with the organic fluorophore FE, 4'-N,N
      diethylamino-3-hydroxyflavone (FE), which possesses fluorescence sensitive to the
      polarity and hydrogen-bonding properties of the surrounding local environment.
      Based on the response of FE in the polymer shell to isopropanol, and CTAB
      compared to the response of free FE we conclude that the FE fluorophore is
      situated within the inner polymer shell. Nevertheless the fluorophore in the
      polymer shell can still sense polarity changes in solution.

PMID- 22383305
TI  - Toxoplasma lymphadenitis mimicking malign axillary lymphadenopathy of a left
      breast mass.
AB  - Toxoplasmosis is an infection caused by the intracellular parasite, Toxoplasma
      gondii. Immunocompetent persons with primary infection are usually asymptomatic,
      but latent infection can persist for the life of the host. There is a risk of
      reactivating infection at a later time should the individual become
      immunocompromised, even if infection was asymptomatic or only mildly symptomatic
      initially. Axillary lymph nodes receive 85% of the lymphatic drainage from the
      breast. Lymph node metastases are relatively common even with invasive breast
      cancers <=1 cm in size. Here, we report a case of toxoplasma lymphadenitis in a
      female adult patient mimicking a malign breast lymphadenopathy of a left breast
      mass.

PMID- 22383306
TI  - Life-threatening bleeding from arterial-oesophageal fistula following
      oesophagectomy.
AB  - Oesophageal carcinoma remains one of the most common forms of cancer. Resection
      in the form of oesophagectomy and gastric interposition remains the standard
      surgical treatment and is associated with a high rate of post-operative
      morbidity. We report a case of a 71-year old male who underwent successful Ivor
      Lewis oesophageal resection and developed life-threatening haemorrhage 2 weeks
      post-op, attributed to an arterial-oesophageal fistula. The patient was
      transferred to a specialist ENT centre with ligation of branches of the carotid
      artery, but intermittent bleeding continued. Following transfer to a specialist
      oesophago-gastric unit, repeated angiography was required to image the point of
      bleeding, which was embolised via percutaneous technique. The etiology,
      presentation, diagnosis and management of arterial-oesophageal fistulae are
      discussed, along with review of existing reports of similar complications and
      treatment options. A multidisciplinary approach, along with timely and often
      repeated imaging, is required in the management of arterial-oesophageal fistulae.

PMID- 22383307
TI  - Cloning and characterization of a panel of constitutive promoters for
      applications in pathway engineering in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is an important platform organism for synthesis of
      chemicals and fuels. However, the promoters used in most pathway engineering
      studies in S. cerevisiae have not been characterized and compared in parallel
      under multiple conditions that are routinely operated in laboratory and the
      number of known promoters is rather limited for the construction of large
      biochemical pathways. Here a total of 14 constitutive promoters from S.
      cerevisiae were cloned and characterized using a green fluorescent protein (GFP)
      as a reporter in a 2 u vector pRS426, under varying glucose and oxygen
      concentrations. The strengths of these promoters varied no more than sixfold in
      the mean fluorescence intensity of GFP, with promoter TEF1p being the strongest
      and promoter PGI1p the weakest. As an example of application for these promoters
      in metabolic engineering, the genes involved in xylan degradation and zeaxanthin
      biosynthesis were subsequently cloned under the control of promoters with medium
      to high strength and assembled into a single pathway. The corresponding construct
      was transformed to a S. cerevisiae strain integrated with a D-xylose utilizing
      pathway. The resulting strain produced zeaxanthin with a titer of 0.74 +/- 0.02
      mg/L directly from birchwood xylan.

PMID- 22383308
TI  - Lifetime obesity in patients with eating disorders: increasing prevalence,
      clinical and personality correlates.
AB  - OBJECTIVES: The aims of our study were to examine the lifetime prevalence of
      obesity rate in eating disorders (ED) subtypes and to examine whether there have
      been temporal changes among the last 10 years and to explore clinical differences
      between ED with and without lifetime obesity. METHODS: Participants were 1383 ED
      female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010,
      to Bellvitge University Hospital. They were assessed by means of the Eating
      Disorders Inventory-2, the Symptom Checklist-90-Revised, the Bulimic
      Investigatory Test Edinburgh and the Temperament and Character Inventory-Revised.
      RESULTS: The prevalence of lifetime obesity in ED cases was 28.8% (ranging from
      5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years,
      there has been a threefold increase in lifetime obesity in ED patients (p <
      .001). People with an ED and obesity had higher levels of childhood and family
      obesity (p < .001), a later age of onset and longer ED duration; and had higher
      levels of eating, general and personality symptomatology. CONCLUSIONS: Over the
      last 10 years, the prevalence of obesity associated with disorders characterized
      by the presence of binge episodes, namely bulimic disorders, is increasing, and
      this is linked with greater clinical severity and a poorer prognosis.

PMID- 22383309
TI  - Trans fat, aspirin, and ischemic stroke in postmenopausal women.
AB  - OBJECTIVE: To examine the associations between dietary fat intake and ischemic
      stroke among postmenopausal women. METHODS: We conducted a prospective cohort
      study of 87,025 generally healthy postmenopausal women (age, 50-79 years)
      enrolled in the Women's Health Initiative Observational Study. Repeated and
      validated dietary assessments were done using a self-administered food frequency
      questionnaire. We used Cox proportional hazards models to estimate hazard ratios
      (HRs) of ischemic stroke based on quintiles of the cumulative average of fat
      intake. RESULTS: We documented 1,049 incident cases of ischemic stroke over
      663,041 person-years of follow-up. Women in the highest quintile of trans fat
      intake had a significantly higher incidence of ischemic stroke (HR, 1.39; 95%
      confidence interval [CI], 1.08-1.79; p-trend = 0.048) compared with women in the
      lowest quintile, while controlling for multiple covariates. The observed
      association was modified by aspirin use (p-interaction = 0.02). The HR was 1.66
      (95% CI, 1.21-2.36; p-trend < 0.01) among baseline non-aspirin users (n = 67,288)
      and 0.95 (95% CI, 0.60-1.48; p-trend = 0.43) among aspirin users (n = 19,736). No
      significant associations were found between intakes of saturated,
      monounsaturated, or polyunsaturated fat and ischemic stroke or any ischemic
      stroke subtypes. INTERPRETATION: In this large cohort of postmenopausal women,
      higher intake of trans fat was associated with incident ischemic stroke
      independent of major lifestyle/dietary factors. Aspirin use may attenuate the
      potential adverse effect of trans fat intake on ischemic stroke.

PMID- 22383311
TI  - Synthesis, characterization, and energetic properties of salts of the 1
      cyanomethyl-1,1-dimethylhydrazinium cation.
AB  - 1,1-Dimethylhydrazine can be readily alkylated with bromoacetonitrile to form 1
      cyanomethyl-1,1-dimethylhydrazinium bromide ([(CH(3))(2)N(CH(2)CN)NH(2)]Br, 1).
      The metathesis reaction of compound 1 led to the formation of a new family of
      energetic salts based on the [(CH(3))(2)N(CH(2)CN)NH(2)](+) cation and nitrate
      (2), perchlorate (3), azide (4), 5-aminotetrazolate ([H(2)N-CN(4)](-), 5), 5,5'
      azobistetrazolate ([N(4)C-N=N-CN(4)](2-), 7), and picrate (8) anions. The new
      materials were characterized by elemental analysis, mass spectrometry, and
      (multinuclear) NMR and vibrational (infrared and Raman) spectroscopies.
      Additionally, the molecular structure of the [(CH(3))(2)N(CH(2)CN)NH(2)](+)
      cation in compounds 1, 3, and 8 and that of sodium 5,5'-azobistetrazolate
      octahydrate (NaZT.8H(2)O) were solved by X-ray diffraction techniques. The
      hydrogen-bonding networks found in the structure of salts 1, 3, 8, and
      NaZT.8H(2)O are described using graph-set analysis. The melting and decomposition
      points of the new compounds were determined by differential scanning calorimetry,
      and insight into their sensitivity towards impact, friction, and electrostatics
      was gained by submitting the materials to standard tests. Furthermore, we
      estimated some performance parameters of interest and predicted the decomposition
      gases formed upon decomposition of salts 2-8 and of mixtures with an oxidizer.
      The interesting thermal, sensitivity, and performance properties of some of the
      compounds described in this work make them attractive towards a prospective
      energetic application.

PMID- 22383310
TI  - Cytoprotective effects of hesperetin and hesperidin against amyloid beta-induced
      impairment of glucose transport through downregulation of neuronal autophagy.
AB  - SCOPE: This study investigated whether flavonoids, such as hesperetin and
      hesperidin, inhibited amyloid beta (Abeta)-impaired glucose utilization through
      regulating cellular autophagy in insulin-stimulated neuronal cells. METHODS AND
      RESULTS: In this study, we used a toxic Abeta1-42 peptide to impair insulin
      stimulated glucose utilization in Neuro-2A cells, and this study also
      hypothesized that Abeta-induced autophagy might be emerging as a key process
      regulating neuronal glucose uptake. Additionally, hesperetin and hesperidin were
      used to test the neuroprotective effect against Abeta-induced impairment of
      glucose utilization. Our data found that Abeta-stimulated autophagy activation
      promoted the phenomenon of impairment of neuronal energy metabolism, including
      glucose uptake, glucose transporters (GLUTs), and insulin signaling cascades. In
      this study, confocal images of autophagy punctate further confirmed that
      downregulation of Abeta-stimulated autophagy could increase insulin-stimulated
      neuronal glucose uptake. Moreover, treatment with hesperetin and hesperidin
      improved Abeta-impaired glucose utilization by inhibiting Abeta-induced autophagy
      in neuronal cells. CONCLUSION: These findings suggest that downregulation of
      autophagy may be one of the approaches to control the impairment of energy
      metabolism leading to neuronal injury in the early development of Alzheimer's
      disease, and hesperetin or hesperidin may be a potential agent in the preventing
      of Alzheimer's disease progression.

PMID- 22383312
TI  - Intracardiac aorto-right atrial tunnel.

PMID- 22383313
TI  - Large thrombosed saccular aneurysm of superior vena cava complicated by pulmonary
      embolism in a young woman.

PMID- 22383314
TI  - Unusual blunt aortic trauma injury.

PMID- 22383315
TI  - Comparison of the peroxidase-like activity of unmodified, amino-modified, and
      citrate-capped gold nanoparticles.
AB  - The origin of the peroxidase-like activity of gold nanoparticles and the impact
      of surface modification are studied. Furthermore, some influencing factors, such
      as fabrication process, redox property of the modifier, and charge property of
      the substrate, are investigated. Compared to amino-modified or citrate-capped
      gold nanoparticles, unmodified gold nanoparticles show significantly higher
      catalytic activity toward peroxidase substrates, that is, the superficial gold
      atoms are a contributing factor to the observed peroxidase-like activity. The
      different catalytic activities of amino-modified and citrate-capped gold
      nanoparticles toward 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) show that the charge
      characteristics of the nanoparticles and the substrate also play an important
      role in the catalytic reactions.

PMID- 22383316
TI  - The safety and efficacy of one-stage bilateral metal-on-metal hip resurfacing
      arthroplasty.
AB  - The objective of this study was to report the perioperative safety and efficacy
      of single-stage, bilateral hip resurfacing arthroplasties (HRAs) in 104 patients.
      The mean preoperative ASA grade was 1.7 + 0.6, and the mean total operative time
      was 3 hours and 31 minutes (+ 32 mins). 13 patients (12.5%) required a homologous
      blood transfusion. Local complications included 5 patients with unilateral,
      serous, incisional drainage after postoperative day 3, with 1 patient (0.9%)
      requiring a superficial irrigation and debridement. One systemic complication
      (0.9%) was noted, as one patient developed atrial fibrillation. There were no
      episodes of femoral neck fracture, deep venous thrombosis, or pulmonary embolism,
      although routine screening for thromboembolic disease was not performed. Hospital
      length of stay averaged 4.1 + 0.9 days, with 76% of patients discharged home. A
      single-stage procedure carries an acceptable complication risk, requires a low
      rate of homologous blood transfusion, and has a low rate of local and systemic
      complications when performed in the appropriately selected patient.

PMID- 22383317
TI  - Avascular necrosis of bilateral femoral heads in a patient with Fabry's disease.
AB  - The underlying cause of avascular necrosis (AVN) of the femoral head is often not
      apparent. We report the case of a 26 year old builder with a four month history
      of bilateral hip pain, and a diagnosis of bilateral femoral head avascular
      necrosis. Fabry's disease was identified as the probable cause. Since 2001,
      enzyme replacement therapy for Fabry's disease has become available, with a
      potential to influence the disease process, and this is of potential importance
      to clinicians treating AVN.

PMID- 22383318
TI  - Randomised trial comparing bone remodelling around two uncemented stems using
      modified Gruen zones.
AB  - For assessment of bone remodelling around total hip arthroplasty using dual
      emission X-ray absorptiometry (DEXA), a variety of different systems to identify
      regions of interest (ROI) have been used, making comparisons between stem designs
      difficult. The Gruen zones are now widely used for this purpose. We present the
      results of a randomised clinical trial comparing 2 uncemented stem designs with
      proximal coating, using a modification of the Gruen zones to allow improved
      representation of the effect of the implant on bone mineral density (BMD) over
      time. DEXA-data were used in a randomised trial with 2 years follow up, comparing
      the uncemented Symax(TM) (n=25) and Omnifit((r)) (n=24) stems. The effect on BMD
      was determined using the 'standard' adapted Gruen zones, and a modification which
      studied an equal length and position for zones 1 and 7 around both stems,
      assuring that the same regions in terms of cancellous and cortical bone were
      compared. The 'modified' regions of interest give lower BMD values around the
      Omnifit((r)) than using the 'standard' Gruen zones (3.6 % in zone 7, p<0.05). The
      difference with the Symax(TM) BMD values, which had been concealed using the
      standard Gruen zones, became statistically significant in favour of the Symax(TM)
      implant. This adaptation can detect a statistically significant difference in
      bone preservation in zone 7 between stems that would otherwise not have been
      revealed. We recommend the use of 'modified' Gruen zones for more valid
      comparison of remodelling caused by different implant designs.

PMID- 22383319
TI  - Superior 11-year survival but higher polyethylene wear of hydroxyapatite-coated
      Mallory-Head cups.
AB  - Hydroxyapatite (HA) coating of implant surfaces is believed to improve longevity
      of uncemented total hip arthroplasty (THA). However; it is speculated that HA
      particles may cause third body wear of the polyethylene (PE) liner with
      subsequent osteolysis and aseptic loosening of implants. We performed a
      retrospective comparison of two patient populations with cementless Mallory-Head
      acetabular components. The patients were identified in the Danish hip
      arthroplasty Registry (DHR); 77 patients had HA-coated cups and 73 patients had
      non-HA coated cups. Anteroposterior (AP) radiographs were analysed for PE wear,
      osteolysis was quantified and survival of the acetabular components was compared.
      The mean follow-up was 11 years. There were no cup revisions in the HA group and
      7 cup revisions in the non-HA group (P<0.01). The reason for revision in all
      cases was aseptic loosening of both stem and cup. The amount of osteolysis was
      significantly increased around cups in the non-HA group. The two-dimensional
      linear PE wear-rate of 0.18 mm/year was higher (P<0.001) in the group with HA
      coated cups compared with 0.12 mm/year in the group with non-HA coated cups. The
      mean age was lower (P=0.001) in the HA group (57 years) compared with the non-HA
      group (63 years). After 11.1 years of follow-up non-HA coated cups had a higher
      revision rate. Increased PE wear with HA-coated cups did not have a negative
      influence on the revision rate, but may result in a need for revision surgery
      over time.

PMID- 22383320
TI  - Outcomes in nonagenarians after hemiarthroplasty for femoral neck fracture. A
      prospective matched cohort study.
AB  - A prospective cohort of 33 nonagenarians with hemiartroplasty for femoral neck
      fracture was matched with 33 patients aged between 70 and 89, using preoperative
      and postoperative data, and the following were studied; epidemiological data,
      physical dependence, and SF-12 and WOMAC questionnaires. The mortality rate at
      one year was 24.2%, influenced by the presence of 3 or more comorbidities,
      dementia, and previous dependence. The perioperative period was the most
      vulnerable time, and in some cases delaying surgery should be considered to
      stabilise the patient's medical condition in very elderly patients. Mortality and
      functional outcomes were worse than in younger patients, but the surgical
      complication rate was similar. Prognostic factors for a decline in quality of
      life were dementia and previous dependence.

PMID- 22383321
TI  - Mortality and morbidity following hip fractures related to hospital
      thromboprophylaxis policy.
AB  - Chemical thromboprophylaxis has been shown to reduce the incidence of venous
      thromboembolism (VTE) for patients with fractures of the hip, but it is not known
      with certainty whether it use also reduces mortality. Using postal and telephone
      questionnaires we collected data from English National Health Service (NHS)
      hospitals about their thromboprophylaxis policy for hip fractures patients from
      April 2003 to April 2007. Using Hospital Episode Statistics (HES) we ascertained
      in-hospital mortality rates at 30 days and at one year following admission to
      hospital. Unplanned hospital readmission rates for all causes (including episodes
      of thromboembolism and bleeding) within 30 days (all years) and one year (2003 to
      2005) were also established. A total of 150 hospitals were contacted and data
      gathered from 62 hospitals (response rate 41.3%) There were 255841 patients with
      neck of femur fractures during this five year period who were assessed for
      morbidity and mortality, and we correlat these with thromboprophylaxis policy.
      There was no significant difference in hospital readmission within 30 days, or
      diagnosis of thromboembolism or haemorrhage among hospitals with different
      thromboprophylaxis policies. The hospitals using low molecular weight heparin
      (LMWH) in half the dose recommended by the British National Formulary had
      significantly reduced mortality in-hospital (odds ratio (OR) 0.79, 95% CI 0.69
      0.90, P=0.0006), at 30 days (OR 0.8 (0.70 - 0.92), P=0.001) and at one year (OR
      0.89 (0.80 - 1.00), P=0.050), compared with those with no such policy. Our data
      suggest that the thromboprophylaxis regimen for patients with fracture neck of
      femur should be half dose LMWH for the duration of the hospital stay.

PMID- 22383322
TI  - Antibiotic addition to cement - is it beneficial.
AB  - Antibiotic loaded acrylic cement (ALAC) is widely employed in primary as well as
      revision hip arthroplasties. There are prerequisites in relation to antibiotic
      choice and mixing techniques. The 2007 French Consensus Conference delivered
      recommendations for ALAC in primary arthroplasty. Decisions need to be more
      patient-specific in revision surgery. Appropriate use of ALAC (and associated
      antibiotics) and awareness of alternative possibilities such as collagen or bone
      graft impregnated with antibiotics may guide future practice.

PMID- 22383323
TI  - The prevalence of cam-type femoroacetabular morphology in young adults and its
      effect on functional hip scores.
AB  - Pelvic computed tomography (CT) scans of forty five young adults were reviewed
      and the alpha angle was calculated. The patients were selected on the basis of an
      age of less than 40 years and the absence of any CT evidence of previous hip
      pathology. An alpha angle of >55o was considered positive for cam morphology. The
      non-arthritic hip score and the University of California Los Angeles activity
      score were completed by the selected group of patients. The mean age of the
      individuals was 33 years (range, 20 to 40). The mean alpha angle at the
      superoinferior position of the anterosuperior quadrant of the femoral neck was
      50.1o on the right side and 49.6o on the left. The prevalence of cam morphology
      was found to be 20% in the right hip and 17.7% in the left hip. There was a
      relatively higher prevalence of cam morphology in men. We also compared the
      functional scores of patients with an alpha angle >55o and those with an alpha
      angle =55o. We found no statistically significant difference between the two
      groups for both scores.

PMID- 22383324
TI  - The Burch-Schneider cage: 9-year survival in Paprosky type 3 acetabular defects.
      Clinical and radiological follow-up.
AB  - Revision hip arthroplasty in cases with severe acetabular deficiency represents a
      technical challenge. The aim of this study was to determine: 1. The 9-year
      survival of the Burch Schneider anti-protrusio cage (BS-APC) in severe acetabular
      defects. 2. The migration of the cage and correlation of this with functional
      outcome. 3. The anticipated functional outcome users can expect in a district
      general hospital setting in the management of severe acetabular defects. A single
      surgeon consecutive series of 30 complex acetabular reconstructions using the BS
      APC was retrospectively reviewed. Clinical and radiological follow up at 5-9
      years was obtained. Survival was established with revisions and further surgery
      as different end-points. A radiological analysis using ein bilt roentgen analyse
      (EBRA) was performed. At a mean follow-up of 85 months (range: 64-118) 26
      patients (87%) were alive. Nine-year survival was 95% for revision of BS-APC as
      an end-point and 92% with any cause of further surgery as an end-point. The mean
      Oxford Hip Score was 34.5 and UCLA activity score was 4.4. All cases demonstrated
      evidence of significant migration, but no screws were found to be broken. There
      was no correlation between cup migration and Oxford hip score (p=0.07). Our non
      specialist centre experience suggests the BS-APC should not be dismissed as a
      reconstruction option in the most severe acetabular defects.

PMID- 22383325
TI  - Transplacental passage of metal ions in women with hip resurfacing: no
      teratogenic effects observed.
AB  - Over recent years, hip resurfacing has been performed in young, active patients,
      including women in their child bearing years. Current work investigating the
      transplacental passage of metal ions (cobalt and chromium) suggests significant
      passage of ions across the placenta in mothers with metal on metal hip
      resurfacing. In vitro studies show that cobalt and chromium can create DNA and
      chromosome damage in human cells. The consequences of this ion transfer on the
      child during fetal development and thereafter have not been fully quantified. We
      report on 3 patients with metal on metal hip resurfacings who had the prosthesis
      in situ during pregnancy. Our data show that umbilical cord blood chromium levels
      are under a quarter of the maternal serum levels. Cord blood cobalt levels are
      approximately half that of maternal blood. All 3 children are healthy. Although
      there was transplacental passage of ions, there was no significant effect on the
      child in these cases. We did not show any teratogenic effect of metal ions on the
      child, and this is consistent with the reported literature.

PMID- 22383326
TI  - The art of filling protein pockets efficiently with octahedral metal complexes.

PMID- 22383327
TI  - Standing CT and clinical progression of equine cholesterol granulomata.

PMID- 22383328
TI  - Peritoneal fluid analysis in dairy cows with left displaced abomasum and abomasal
      volvulus.
AB  - Peritoneal fluid (PF) was evaluated in 40 cows with left displaced abomasum (LDA)
      and 15 cows with abomasal volvulus (AV). PF was obtained by abdominocentesis at
      the right ventral abdomen at admission. Simultaneously, a blood sample was taken
      from the jugular vein. Biochemical and cytological variables in blood and PF
      specific for ischaemia, inflammation and cell damage were compared. Total
      protein, albumin, glucose and cholesterol were normal in PF of cows with LDA and
      AV. Although L-lactate increased in both groups, cows with AV had significantly
      higher values (LDA: 1.47/0.69/2.68 mmol/l; AV: 6.45/4.55/12.89 mmol/l (median/1.
      quartile/3. quartile)). D-dimer (LDA: 0.50/0.22/0.88 mg/l; AV: 1.11/0.40/1.85
      mg/l) and LDH (LDA: 663/437/943 U/l; AV: 1099/750/1439 U/l) were only increased
      in PF of cows with AV. The number of leucocytes was normal; however,
      significantly more peritoneal neutrophils appeared necrotic or apoptotic after
      AV. PF of cows with abomasal displacement showed distinctive features of
      ischaemia and inflammation. Characteristics of haemostatic dysfunction and cell
      damage were mainly evident in PF of cows with AV. The results suggest that anti
      inflammatory therapy is indicated in each cow with abomasal displacement.
      Additionally, medical treatment should be directed to prevent complications of
      ischaemia and reperfusion in cows with AV.

PMID- 22383329
TI  - Long-term study of MRSA ST1, t127 mastitis in a dairy cow.

PMID- 22383330
TI  - Metabolism of small antimicrobial beta(2,2)-amino acid derivatives by murine
      liver microsomes.
AB  - We have investigated the in vitro metabolism of three small antimicrobial
      beta(2,2)-amino acid derivatives (M (w) < 500) that are highly potent against
      methicillin resistant Staphylococcus aureus, and are among the first compounds
      designed from small cationic antimicrobial peptides with potential for oral
      administration. The beta(2,2)-amino acid derivatives are virtually completely
      resistant against degradation by proteases, and to further explore their drug
      potential, we have investigated the hepatic Phase I metabolism of this class of
      antimicrobial compounds. The beta(2,2)-amino acid derivatives were incubated with
      murine liver microsomes and the metabolites analyzed semi-quantitatively by HPLC
      MS and qualitatively by ultra performance liquid chromatography coupled to a
      tandem mass spectrometer which enabled identification of the metabolites by
      careful interpretation of the collision activated dissociation spectra. The study
      shows that sterically hindered beta(2,2)-amino acid derivatives that otherwise
      are stable against proteolytic degradation underwent Phase I metabolism and were
      oxidized to a number of different metabolites depending on the structure of the
      beta(2,2)-amino acid side-chains.

PMID- 22383331
TI  - Characterizing the protocol for early modified constraint-induced movement
      therapy in the EXPLICIT-stroke trial.
AB  - Constraint-induced movement therapy (CIMT) is a commonly used rehabilitation
      intervention to improve upper limb function after stroke. CIMT was originally
      developed for patients with a chronic upper limb paresis. Although there are
      indications that exercise interventions should start as early as possible after
      stroke, only a few randomized controlled trials have been published on either
      CIMT or modified forms of CIMT (mCIMT) during the acute phase after stroke. The
      implementation of (m)CIMT in published studies is very heterogeneous in terms of
      content, timing and intensity of therapy. Moreover, mCIMT studies often fail to
      provide a detailed description of the protocol applied. The purpose of the
      present paper is therefore to describe the essential elements of the mCIMT
      protocol as developed for the EXplaining PLastICITy after stroke (EXPLICIT
      stroke) study. The EXPLICIT-stroke mCIMT protocol emphasizes restoring body
      functions, while preventing the development of compensatory movement strategies.
      More specifically, the intervention aims to improve active wrist -and finger
      extension, which is assumed to be a key factor for upper limb function. The
      intervention starts within 2 weeks after stroke onset. The protocol retains two
      of the three key elements of the original CIMT protocol, that is, repetitive
      training and the constraining element. Repetitive task training is applied for 1
      hour per working day, and the patients wear a mitt for at least 3 hours per day
      for three consecutive weeks.

PMID- 22383332
TI  - Efficient regioselective synthesis and potential antitumor evaluation of
      isoxazolo[5,4-b]pyridines and related annulated compounds.
AB  - The reaction of 5-amino-3-methylisoxazole with appropriate alpha,beta-unsaturated
      ketones gave the corresponding isoxazolo[5,4-b]pyridines. Treatment of 1 with 2,6
      dibenzylidenecyclohexanone or 2-benzylidenedimedone afforded the corresponding
      isoxazolo[5,4-b]quinoline derivatives. 4,6,8,9-Tetrahydroisoxazolo[5,4-b]quinolin
      5-one derivative was also obtained by multicomponent condensation reaction of 1
      with dimedone and benzaldehyde. Heterocyclic annulation of the isoxazolo[5,4
      b]pyridine system was achieved via reaction of 1 with benzylidene derivatives of
      indandione, quinuclidone, pyrazolone, and oxazolone. A representative of some
      newly synthesized compounds was evaluated as antitumor agents.

PMID- 22383333
TI  - Effect of dispersion on the structure and dynamics of the ionic liquid 1-ethyl-3
      methylimidazolium thiocyanate.
AB  - We present a comprehensive density functional study, using the Perdew-Burke
      Ernzerhof (PBE) functional, to elucidate the effect of including or neglecting
      the dispersion correction on the structure and dynamics of the ionic liquid 1
      ethyl-3-methylimidazolium thiocyanate. We have investigated the structure of the
      liquid phase and observed that specific interactions between the anions and
      cations of the ionic liquid were not accurately represented if the dispersion was
      neglected. The dynamics of the system is more accurately described if the
      dispersion correction is taken into account and its omission also leads to an
      incorrect representation of the hydrogen-bonding dynamics. Finally, the power
      spectrum is predicted and in good agreement with experimental results. Thus, we
      conclude that it is possible to represent the structure and dynamics of systems
      containing ionic liquids accurately using ab initio molecular dynamics and a
      correction for dispersion.

PMID- 22383334
TI  - Carbon nanomaterials for advanced energy conversion and storage.
AB  - It is estimated that the world will need to double its energy supply by 2050.
      Nanotechnology has opened up new frontiers in materials science and engineering
      to meet this challenge by creating new materials, particularly carbon
      nanomaterials, for efficient energy conversion and storage. Comparing to
      conventional energy materials, carbon nanomaterials possess unique size-/surface
      dependent (e.g., morphological, electrical, optical, and mechanical) properties
      useful for enhancing the energy-conversion and storage performances. During the
      past 25 years or so, therefore, considerable efforts have been made to utilize
      the unique properties of carbon nanomaterials, including fullerenes, carbon
      nanotubes, and graphene, as energy materials, and tremendous progress has been
      achieved in developing high-performance energy conversion (e.g., solar cells and
      fuel cells) and storage (e.g., supercapacitors and batteries) devices. This
      article reviews progress in the research and development of carbon nanomaterials
      during the past twenty years or so for advanced energy conversion and storage,
      along with some discussions on challenges and perspectives in this exciting
      field.

PMID- 22383335
TI  - Simple ligand effects switch a hydrogenase mimic between H2 and O2 activation.
AB  - Herein, we report a [NiRu] biomimetic system for O(2)-tolerant [NiFe]hydrogenases
      and demonstrate that electron donation to the [NiRu] center can switch the system
      between the activation of H(2) and O(2) through simple ligand effects by using
      hexamethylbenzene and pentamethylcyclopentadienyl ligands, respectively.
      Furthermore, we present the synthesis and direct observations of a [NiRu]-peroxo
      species, which was formed by the oxygenation of a Ni-SIa model [NiRu] complex,
      that we propose as a biomimetic analogue of O(2)-bound species (OBS) of O(2)
      tolerant [NiFe]hydrogenases. The [NiRu]-peroxo complex was fully characterized by
      X-ray analysis, X-ray photoelectron spectroscopy (XPS), mass spectrometry, and
      (1)H NMR spectroscopy. The OBS analogue was capable of oxidizing p-hydroquinone
      and sodium borohydride to turn back into the Ni-SIa model complex.

PMID- 22383336
TI  - Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long
      acting release in healthy volunteers: a single-center Phase I study.
AB  - OBJECTIVE: This study was conducted to evaluate the safety, tolerability, and
      pharmacokinetics (PKs) of different doses of a long-acting release (LAR)
      formulation of pasireotide in healthy subjects. DESIGN: Single-center, open
      label, randomized Phase I study. METHODS: Twelve healthy male subjects received a
      single s.c. dose of pasireotide 300 MUg followed by a washout period of 7 days
      (or at least 5 days), before receiving an i.m. injection of pasireotide -LAR 40
      mg (n=5) or 60 mg (n=7). Assessments included adverse events (AEs), PKs, and
      glucose, insulin, glucagon, and HbA1c levels. RESULTS: Pasireotide LAR showed an
      extended-release profile over 1 month with two concentration peaks observed 1 and
      around 20 days after injection. The area under curve exposure of pasireotide LAR
      was dose proportional when the dose levels were compared, and the bioavailability
      of the LAR relative to the s.c. formulation was complete. Administration of
      pasireotide LAR resulted in an increase in fasting and postprandial glucose
      levels; however, an attenuation of the hyperglycemic effect was observed after 15
      days. The most frequently reported AEs were mild-to-moderate diarrhea, abdominal
      pain, and flatulence. Only gastrointestinal AEs and injection site reactions were
      suspected to be drug related. CONCLUSIONS: Pasireotide LAR was generally well
      tolerated with mostly mild AEs at doses up to 60 mg and showed a dose
      proportional, extended-release profile in healthy subjects. Based on the
      favorable results of this study, further clinical development of pasireotide LAR
      is under way, which will give insight into the PKs, efficacy, and safety of
      pasireotide LAR in patient populations.

PMID- 22383337
TI  - The O-carbamoyltransferase TobZ catalyzes an ancient enzymatic reaction.

PMID- 22383340
TI  - Kinetics of adsorption, desorption, and re-adsorption of a commercial
      endoglucanase in lignocellulosic suspensions.
AB  - This study conducted quantitative kinetic modeling and in situ and temporally
      resolved measurements of adsorption, desorption, and re-adsorption of a
      commercial endoglucanase in lignocellulosic suspensions. The study defined a
      cellulase adsorption and desorption competition parameter, a pseudo rate of
      binding and desorption, binding and desorption capacity, as well as cellulase
      binding reversibility (a thermodynamic property) and recyclability (a engineering
      parameter). The results indicate that both substrate chemical and physical
      structures play important roles in cellulase binding and desorption. Binding of a
      commercial cellulase onto a cellulosic substrate was reversible. Bindings to two
      different lignocellulosic substrates were almost irreversible. While lignin and
      its structure positively affect binding capacity to substrate, they negatively
      affect cellulase recyclability. Collapsing of substrate pores reduced cellulose
      accessibility and cellulase-binding capacity and increased reversibility and
      recyclability. Increasing temperature and pH increase cellulase desorption and
      increased binding reversibility and capacity. This study lays the foundation for
      developing effective cellulase recycling strategies.

PMID- 22383341
TI  - Active visual segmentation.
AB  - Attention is an integral part of the human visual system and has been widely
      studied in the visual attention literature. The human eyes fixate at important
      locations in the scene, and every fixation point lies inside a particular region
      of arbitrary shape and size, which can either be an entire object or a part of
      it. Using that fixation point as an identification marker on the object, we
      propose a method to segment the object of interest by finding the "optimal"
      closed contour around the fixation point in the polar space, avoiding the
      perennial problem of scale in the Cartesian space. The proposed segmentation
      process is carried out in two separate steps: First, all visual cues are combined
      to generate the probabilistic boundary edge map of the scene; second, in this
      edge map, the "optimal" closed contour around a given fixation point is found.
      Having two separate steps also makes it possible to establish a simple feedback
      between the mid-level cue (regions) and the low-level visual cues (edges). In
      fact, we propose a segmentation refinement process based on such a feedback
      process. Finally, our experiments show the promise of the proposed method as an
      automatic segmentation framework for a general purpose visual system.

PMID- 22383342
TI  - Model-based learning using a mixture of mixtures of Gaussian and uniform
      distributions.
AB  - We introduce a mixture model whereby each mixture component is itself a mixture
      of a multivariate Gaussian distribution and a multivariate uniform distribution.
      Although this model could be used for model-based clustering (model-based
      unsupervised learning) or model-based classification (model-based semi-supervised
      learning), we focus on the more general model-based classification framework. In
      this setting, we fit our mixture models to data where some of the observations
      have known group memberships and the goal is to predict the memberships of
      observations with unknown labels. We also present a density estimation example. A
      generalized expectation-maximization algorithm is used to estimate the parameters
      and thereby give classifications in this mixture of mixtures model. To simplify
      the model and the associated parameter estimation, we suggest holding some
      parameters fixed-this leads to the introduction of more parsimonious models. A
      simulation study is performed to illustrate how the model allows for bursts of
      probability and locally higher tails. Two further simulation studies illustrate
      how the model performs on data simulated from multivariate Gaussian distributions
      and on data from multivariate t-distributions. This novel approach is also
      applied to real data and the performance of our approach under the various
      restrictions is discussed.

PMID- 22383343
TI  - Pretransplant serum phosphate levels and outcomes after kidney transplantation.
AB  - BACKGROUND: The relation between serum phosphate control while on dialysis and
      kidney transplant outcomes is uncertain. Our study assessed the effect of
      pretransplant serum phosphate levels (PTxP) on kidney transplant outcomes.
      METHODS: Hemodialysis patients included in the Dialysis Morbidity and Mortality
      Study of the US Renal Data System, undergoing kidney transplantation were studied
      (n=801). Delayed graft function (DGF) and graft failure as a function of PTxP,
      were assessed using multivariable logistic and Cox regression models. RESULTS:
      The within-quartile medians (interquartile range) of PTxP were 4.2 (3.7-4.5), 5.4
      (5.1-5.7), 6.4 (6.1-6.8) and 8.5 (7.7-9.7) mg/dL. The adjusted odds ratio (OR)
      for DGF was significantly elevated for the fourth vs. first PTxP quartiles
      (OR=1.68; 95% confidence interval [95% CI], 1.05-2.71). Restricting the cohort to
      patients transplanted prior to the publication of the KDOQI bone metabolism and
      disease guidelines, PTxP measured within 1-year of transplant, or deceased donor
      recipients generally showed similar results. The adjusted hazard ratios for death
      censored graft failure increased across PTxP quartiles (p for trend = 0.015).
      CONCLUSION: Higher PTxP is associated with an increased risk of adverse kidney
      allograft outcomes including DGF and death-censored graft failure. This suggests
      an important additional benefit of optimizing phosphate control in patients
      awaiting kidney transplantation while on dialysis.

PMID- 22383344
TI  - Effect of serum electrolyte and bicarbonate concentration changes during
      hemodialysis sessions on heart rate variability.
AB  - INTRODUCTION: Heart rate variability (HRV) is decreased in dialysis patients, and
      decreased HRV is an independent risk factor for sudden cardiac death. We aimed to
      determine the effect of sudden changes in serum electrolyte, bicarbonate
      concentration and blood pressure on HRV during hemodialysis (HD) sessions in
      chronic HD patients. METHODS: The study population included 75 HD patients (mean
      age 44.5 +/- 10.3 years; 53% female, 13% diabetic) and 35 healthy volunteers
      (mean age 42.44 +/- 11.5 years, 62% female). HRV indexes were analyzed from 24
      hour ECG recordings. The time-domain HRV indexes (SDNN, SDANN, RMSSD, pNN50 [%]
      and HRV TAI) were calculated from these recordings. Pre- and post-HD blood
      samples were drawn from an arterial line to calculate Na+, K+, Ca2+, iCa2+ and
      HCO3- concentration gradients. RESULTS: All HRV indexes were significantly lower
      in dialysis patients than in healthy volunteers (p<0.05).The detected SDNN and
      HRV TAI values were lower in diabetic patients than in nondiabetics. While K+
      concentration was decreased, Ca2+ and bicarbonate increased significantly during
      HD. CONCLUSION: HRV decreased in chronic HD patients. The decrease in HRV in
      diabetic uremic patients was higher than in uremic patients without diabetes. The
      change of serum electrolyte and bicarbonate concentrations during HD did not
      affect HRV.

PMID- 22383345
TI  - Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal
      failure and renal transplant patients: a role for FGF23.
AB  - INTRODUCTION: Vitamin D insufficiency contributes to calcitriol (1,25D) reduction
      in chronic kidney disease (CKD). Since CKD patients on conservative therapy (CRF)
      mostly develop, whereas transplant (TX) patients possibly recover from, secondary
      hyperparathyroidism (SH), we hypothesized a different efficiency of vitamin D
      hydroxylation in these 2 clinical conditions. METHODS: We compared the impact of
      reduced 25-hydroxyvitamin D (25D) on circulating 1,25D in 111 CRF (mean age 63 +/
      15 years; estimated glomerular filtration rate [eGFR] 36.4 +/- 22.0 ml/min) and
      in 136 TX patients (mean age 50 +/- 11 years; eGFR 47 +/- 19.0 ml/min). RESULTS:
      Vitamin D insufficient patients (69.1% in TX vs. 82% in CRF; p<0.005), compared
      with those without insufficiency, had lower values of 1,25D in CRF (24.5 +/- 17.4
      vs 35.8 +/- 17.8 pg/mL; p<0.01) but not in TX (42.7 +/- 23.8 vs. 50.1 +/- 25.4
      pg/mL; p=n.s.). Serum 25D and 1,25D were correlated in both CRF (r=0.387,
      p<0.0001) and TX (r=0.240, p0<.005) groups, but 1,25D values were higher in the
      TX group in any of the 4 ranges for 25D considered. Serum calcitriol correlated
      with eGFR (CRF: r=0.641, p<0.0001; TX: r=0.426, p<0.0001), but again with higher
      values in the TX group, in any of the CKD stages considered, except stage 2. In
      both conditions, the most predictive parameter of 1,25D levels was eGFR, together
      with phosphate and 25D in the CRF group (r2=0.545; p<0.0001), and with Ca and 25D
      in the TX group (r2=0.345; p<0.0001). In 2 subgroups, comparable for eGFR and
      25D, levels of FGF23 were lower in the TX group, in agreement with higher values
      of 1,25D. CONCLUSIONS: A 25D deficit more significantly affects calcitriol
      concentrations in CRF as compared with TX. Efficiency of vitamin D hydroxylation
      should be considered when planning vitamin D replacement strategies.

PMID- 22383346
TI  - Indications and results of renal biopsy in children: a 10-year review from a
      single center in Serbia.
AB  - BACKGROUND: This study was conducted to retrospectively investigate the
      indications for renal biopsy in native kidneys and to analyze pathological
      findings in the last 10 years in a single tertiary pediatric hospital in Serbia.
      METHODS: All patients who underwent renal biopsy at our hospital between 2001 and
      2010 were included in the present study. Renal biopsy was performed under
      fluoroscopy with a biopsy gun. All renal biopsies were studied under light and
      immunofluorescent microscopy, while electron microscopy was rarely performed.
      RESULTS: The study group included 150 patients (56% female) who underwent 158
      percutaneous native kidney biopsies. Median age was 11.5 years (range 0.2-20
      years). The most frequent indications for renal biopsy were nephrotic syndrome
      (32.9%), asymptomatic hematuria (23.4%), urinary abnormalities in systemic
      diseases (15.8%) and proteinuria (11.4%). Primary glomerulonephritis (GN) was the
      most common finding (57.4%), followed by secondary GN (15.5%) and
      tubulointerstitial diseases (4.5%). According to histopathological diagnosis, the
      most common causes of primary GN were focal segmental glomerulosclerosis (20.9%),
      mesangioproliferative GN (14.6%), IgA nephropathy (8.9%) and minimal change
      disease (13%). Lupus nephritis (6%) and Henoch-Schonlein nephritis (4%) were the
      most common secondary glomerular diseases. CONCLUSIONS: The epidemiology of
      glomerular disease in our single-center report is similar to that in data from
      adjacent Croatia and Greece. Focal segmental glomerulosclerosis was the dominant
      histopathological finding, followed by mesangioproliferative GN and IgA
      nephropathy.

PMID- 22383347
TI  - Incidence of contrast-induced acute kidney injury associated with diagnostic or
      interventional coronary angiography.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) represents an important
      cause of hospital-acquired AKI. The aim of this study was to evaluate the
      incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary
      intervention (PCI) and the role of patient-/procedure-related risk factors.
      METHODS: For 11 months, patients undergoing CA or PCI were prospectively
      evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed.
      Statistical analysis was completed using Student's t-test, chi-square or Fisher
      exact test, and multivariate logistic regression. RESULTS: Among 585 consecutive
      patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was
      required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with
      anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin
      was significantly lower in CI-AKI patients while Mehran score, contrast medium
      (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio
      glomerular filtration rate (CM volume / GFR) were significantly higher.
      Multivariate analysis selected a higher contrast ratio as a factor independently
      associated with a higher risk of CI-AKI which otherwise appeared to be lower with
      increasing basal hemoglobin. CONCLUSIONS: The incidence of CI-AKI after CA or PCI
      was higher in patients with CKD associated with diabetes. Lower levels of basal
      hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media
      volume, especially if exceeding the dose adjusted for renal function, was a
      strong modifiable risk factor for CI-AKI.

PMID- 22383348
TI  - Serum HSP27 is associated with medullary perfusion in kidney allografts.
AB  - BACKGROUND: Heat shock protein 27 (HSP27) is a small HSP up-regulated in response
      to stress in the kidney. The relationship between HSP27 and intrarenal
      oxygenation in patients with native and transplant kidney disease is unknown.
      METHODS: We compared HSP27 levels, intrarenal oxygenation measured by blood
      oxygen-level dependent (BOLD) imaging using R(2)* values, and perfusion
      determined by arterial spin labeling (ASL) magnetic resonance imaging (MRI),
      between patients with native and transplant kidney disease (n=28). RESULTS: There
      were no statistical differences in mean age (53.9 vs. 47.1 years), kidney
      function (63.6 vs. 50.7 ml/min per 1.73 m(2)), mean arterial blood pressure (91.6
      vs. 91.1 mm Hg), hematocrit (40.6% vs. 39.3%), diuretic or angiotensin-converting
      enzyme inhibitor use, serum or urine levels of hydrogen peroxide, nitric oxide,
      F(2) isoprostanes and HSP27 between native and transplant kidneys. BOLD-MRI
      studies demonstrated comparable patterns in intrarenal oxygen bioavailability
      (medullary R(2)* 18.1 vs. 18.3/s and cortical R(2)* 12 vs. 11.7/s, respectively).
      However, medullary perfusion was significantly lower in transplant kidneys (36.4
      vs. 78.7 ml/100 g per minute, p=0.0002). There was a linear relationship between
      serum HSP27 concentrations and medullary perfusion in kidney allografts (HSP27
      concentration [ng/mL] = 0.78 + 0.09 medullary perfusion, R(2)=0.43, p=0.01).
      CONCLUSIONS: Our study demonstrates that medullary perfusion is significantly
      lower in kidney allografts compared with native kidneys with comparable renal
      function. We further noted a direct association between serum HSP27 levels and
      medullary perfusion after transplantation. Additional studies are needed to
      examine the role of HSP27 as a biomarker of kidney disease progression.

PMID- 22383349
TI  - Echocardiographic abnormalities in patients on kidney transplant waiting list.
AB  - BACKGROUND: Echocardiographic abnormalities are well described in chronic kidney
      disease (CKD), and associated with increased cardiovascular events (CVEs) and
      mortality. Little is known regarding progression of these abnormalities in
      patients awaiting kidney transplantation. METHODS: We assessed the progression of
      echocardiographic variables in patients awaiting kidney transplantation and
      determined predictors of CVEs and mortality. The study included all patients
      awaiting kidney transplantation between 2004 and 2010 with repeat echocardiograms
      at least 1 year apart and at least 1 year after transplantation. RESULTS: We
      assessed 79 patients (57% male, mean age 55 +/- 11 years; 27% with diabetes).
      Sixty-three patients remained on waiting list, and 16 had kidney transplants. Two
      deaths and 2 CVEs occurred in patients awaiting kidney transplantation. Repeat
      echocardiograms (31 +/- 19 months from baseline) on patients who remained on
      waiting list showed significant increases in left ventricular mass index (LVMI)
      (55.3 +/- 17.8 vs. 60.5 +/- 21.9 g/m2.7, p=0.02) and in left atrium (LA) diameter
      (3.8 +/- 0.6 vs. 4.1 +/- 0.8 cm, p=0.02). There were no significant changes in LV
      fractional shortening (FS) or LV end-systolic and end-diastolic dimensions. Left
      atrium diameter (p=0.005), systolic dysfunction (p=0.007) and LVMI (p=0.01) were
      independent predictors of CVEs and mortality. CONCLUSIONS: Time on kidney
      transplant waiting list is associated with progressive increases in LA diameter
      and LVM, which are markers of adverse outcome.

PMID- 22383350
TI  - Can we identify patients with microscopic polyangiitis who are at risk of
      relapse?

PMID- 22383351
TI  - Mortality and multiple causes of death in systemic lupus erythematosus -- role of
      the death certificate.

PMID- 22383352
TI  - Teriparatide for glucocorticoid-induced osteoporosis.

PMID- 22383353
TI  - Miliary nodularity in a patient receiving TNF inhibitors is not always miliary
      tuberculosis.

PMID- 22383354
TI  - Patient assessments of skin, joint, and nail disease activity in psoriatic
      arthritis.

PMID- 22383355
TI  - Whiplash: nothing to lose sleep over.

PMID- 22383356
TI  - Psoriasis onset with tocilizumab treatment for rheumatoid arthritis.

PMID- 22383357
TI  - Acute inflammatory syndrome with elevated procalcitonin induced by mycophenolate
      sodium.

PMID- 22383358
TI  - Febuxostat hypersensitivity.

PMID- 22383359
TI  - Nodular/keloidal scleroderma: acquired collagenous nodules in systemic sclerosis.

PMID- 22383360
TI  - Central nervous system vasculitis: all that glitters is not gold.

PMID- 22383361
TI  - Radiographic improvement in sarcoid arthropathy after infliximab treatment.

PMID- 22383362
TI  - Myopericarditis revealing giant cell arteritis in the elderly.

PMID- 22383363
TI  - Porous protein crystals as reaction vessels for controlling magnetic properties
      of nanoparticles.
AB  - Magnetic bimetallic CoPt nanoparticles are synthesized in the solvent channels of
      hen egg white lysozyme crystals by the reduction of Co(2+)  and Pt(2+)  ions pre
      organized on the interior surface of the solvent channels. By using different
      lysozyme crystal systems, the magnetic properties of CoPt nanoparticles can be
      controlled.

PMID- 22383364
TI  - Iodine(III)-promoted intermolecular diamination of alkenes.
AB  - A rapid and productive vicinal diamination of alkenes takes place in the presence
      of a hypervalent iodine(III) reagent and bissulfonimides as nitrogen sources. A
      total of more than 60 examples are presented. The reaction is characterized by
      its robustness and its wide substrate scope: it proceeds selectively with both
      terminal and internal alkenes and tolerates a range of functional groups.

PMID- 22383365
TI  - Evaluation and interpretation of the effects of environmental enrichment
      utilizing varying degrees of sampling effort.
AB  - Documenting the effects of novel forms of enrichment is becoming increasingly
      important within the field of environmental enrichment. Appropriate documentation
      and evaluation must accompany any enrichment research project in order for
      accurate results to be obtained. The objective of the present study was to
      provide an example of how the level of effort in documenting the effect of
      enrichment is linked to how it is evaluated. This study was carried out on eight
      cheetahs (Acinonyx jubatus) at Fota Wildlife Park, Ireland. Temporal feeding
      variation was the enrichment type used during this study. Behavior data were
      collected in five different ways in order to simulate varying degrees of effort.
      Randomization tests were utilized to analyze behavior data. Significant
      behavioral differences were observed in the first four sampling methods with
      patterns of behavior remaining similar in all five methods. However, only the
      most time intensive method concurred with findings previously published utilizing
      this form of enrichment. No significant differences in behavior were detected
      when the least time intensive method was used. Between 1 and 2 hr of data
      collection daily is necessary to evaluate temporal feeding variation accurately.
      However, 30-45 min of data collection also gave an insight into the effectiveness
      of the enrichment. Methods of evaluation can influence the interpretations of the
      strength of the enriching effect of the treatment. Appropriate evaluation and
      accurate reporting of enrichment is crucial for the future development of the
      environmental enrichment field.

PMID- 22383366
TI  - Temperature dependence of the dielectric permittivity of acetic acid, propionic
      acid and their methyl esters: a molecular dynamics simulation study.
AB  - For most liquids, the static relative dielectric permittivity is a decreasing
      function of temperature, because enhanced thermal motion reduces the ability of
      the molecular dipoles to orient under the effect of an external electric field.
      Monocarboxylic fatty acids ranging from acetic to octanoic acid represent an
      exception to this general rule. Close to room temperature, their dielectric
      permittivity increases slightly with increasing temperature. Herein, the causes
      for this anomaly are investigated based on molecular dynamics simulations of
      acetic and propionic acids at different temperatures in the interval 283-363 K,
      using the GROMOS 53A6(OXY)  force field. The corresponding methyl esters are also
      considered for comparison. The dielectric permittivity is calculated using either
      the box-dipole fluctuation (BDF) or the external electric field (EEF) methods.
      The normal and anomalous temperature dependences of the permittivity for the
      esters and acids, respectively, are reproduced. Furthermore, in the EEF approach,
      the response of the acids to an applied field of increasing strength is found to
      present two successive linear regimes before reaching saturation. The low-field
      permittivity epsilon, comparable to that obtained using the BDF approach,
      increases with increasing temperature. The higher-field permittivity epsilon' is
      slightly larger, and decreases with increasing temperature. Further analyses of
      the simulations in terms of radial distribution functions, hydrogen-bonded
      structures, and diffusion properties suggest that increasing the temperature or
      the applied field strength both promote a relative population shift from cyclic
      (mainly dimeric) to extended (chain-like) hydrogen-bonded structures. The lower
      effective dipole moment associated with the former structures compared to the
      latter ones provides an explanation for the peculiar dielectric properties of the
      two acids compared to their methyl esters.

PMID- 22383367
TI  - Use of focused acoustics for cell disruption to provide ultra scale-down insights
      of microbial homogenization and its bioprocess impact--recovery of antibody
      fragments from rec E. coli.
AB  - An ultra scale-down (USD) device that provides insight of how industrial
      homogenization impacts bioprocess performance is desirable in the
      biopharmaceutical industry, especially at the early stage of process development
      where only a small quantity of material is available. In this work, we assess the
      effectiveness of focused acoustics as the basis of an USD cell disruption method
      to mimic and study high-pressure, step-wise homogenization of rec Escherichia
      coli cells for the recovery of an intracellular protein, antibody fragment
      (Fab'). The release of both Fab' and of overall protein follows first-order
      reaction kinetics with respect to time of exposure to focused acoustics. The rate
      constant is directly proportional to applied electrical power input per unit
      volume. For nearly total protein or Fab' release (>99%), the key physical
      properties of the disruptate produced by focused acoustics, such as cell debris
      particle size distribution and apparent viscosity show good agreement with those
      for homogenates produced by high-pressure homogenization operated to give the
      same fractional release. The only key difference is observed for partial
      disruption of cells where focused acoustics yields a disruptate of lower
      viscosity than homogenization, evidently due to a greater extent of polynucleic
      acids degradation. Verification of this USD approach to cell disruption by high
      pressure homogenization is achieved using USD centrifugation to demonstrate the
      same sedimentation characteristics of disruptates prepared using both the scaled
      down focused acoustic and the pilot-scale homogenization methods for the same
      fraction of protein release.

PMID- 22383368
TI  - X-ray imaging of zeolite particles at the nanoscale: influence of steaming on the
      state of aluminum and the methanol-to-olefin reaction.

PMID- 22383369
TI  - The diaryl(oxy)methyl group: more than an innocent bystander in chiral
      auxiliaries, catalysts, and dopants.
AB  - Either as the free alcohol or deprotonated, a carbinol residue bearing gemial,
      identical aryl residues can at first sight be recognized as an achiral structural
      unit. When incorporated, however, into a chiral molecule, the two aryl groups
      become diastereotopic. Thus, they might contribute to an enhancement in
      stereoselectivity and do so in a variety of reactions. This Minireview highlights
      developments in stereochemistry when the diaryl(oxy)methyl group is involved,
      with emphasis given to the beneficial effect of this moiety. Of particular focus
      are auxiliaries, the stoichiometric use of metal complexes, metal and
      organocatalysts, and finally chiral dopants for liquid crystals, all featuring
      the diaryl(oxy)methyl group.

PMID- 22383370
TI  - On the lifetime of the transients (NP)-(CH3)n (NP = Ag0, Au0, TiO2 nanoparticles)
      formed in the reactions between methyl radicals and nanoparticles suspended in
      aqueous solutions.
AB  - Methyl radicals react in fast reactions, with rate constants k>1*10(8)  M(-1)  s(
      1), with Au(0), Ag(0) and TiO(2) nanoparticles (NPs) dispersed in aqueous
      solutions to form intermediates, (NP)-(CH(3))(n), in which the methyl groups are
      covalently bound to the NPs. These intermediates decompose to form ethane. As
      n>=2 is required for the formation of C(2)H(6), the minimal lifetime (tau) of the
      methyls bound to the NPs, (NP)-CH(3), can be estimated from the rate of
      production of the CH(3)(.) radicals and the NPs concentration. The results
      obtained in this study, using a very low dose rate gamma-source for NP = Ag(0),
      Au(0), and TiO(2) point out that tau of these intermediates is surprisingly long,
      for example, >=8 and >=188 sec for silver and gold, respectively. These data
      point out that the NP-C bond dissociation energies are >=70 kJ  mol(-1). Under
      low rates of production of CH(3)(.), that is, when the rate of formation of
      ethane is very low, other reactions may occur, consequently the mechanism
      proposed is "broken". This is observed in the present study only for TiO(2) NPs.
      These results have to be considered whenever alkyl radicals are formed near
      surfaces. Furthermore, the results point out that the rate of reaction of methyl
      radicals with (NP)-(CH(3))(n) depends on n, that is, the number of methyl
      radicals bound to the NPs affect the properties of the NPs.

PMID- 22383372
TI  - Myocardial systolic and diastolic consequences of left ventricular mechanical
      dyssynchrony in heart failure with normal left ventricular ejection fraction.
AB  - AIMS: The purpose of this study was to test the hypothesis that left ventricular
      (LV) mechanical dyssynchrony deteriorates the longitudinal systolic and diastolic
      function of the left ventricle (LV) in patients with heart failure with a normal
      LV ejection fraction (HFNEF). METHODS AND RESULTS: In patients with HFNEF and in
      a control group consisting of asymptomatic patients with LV diastolic dysfunction
      [LVDD], matched by age, gender, and LV ejection fraction, we assessed the global
      longitudinal systolic (global strain), diastolic [global early-diastolic strain
      rate (SRe)], and synchronous (standard deviation of time-to-peak systolic strain)
      function of the LV by two-dimensional speckle-tracking echocardiography using a
      18-segment LV model. A total of 325 patients were included (85 with HFNEF and 240
      with asymptomatic LVDD). Patients with HFNEF had a significant impairment of the
      longitudinal systolic and diastolic function of the LV as compared with the
      control group. Concerning the pathophysiological mechanisms linked to these
      findings, we found that HFNEF patients with asynchronous LV contractions had
      significantly more impaired longitudinal systolic and diastolic LV function
      (global strain -14.76 +/- 3.44%, global SRe 0.79 +/- 0.24 s(-1)) than patients
      without asynchronous LV contractions (global strain -18.57 +/- 3.10%, global SRe
      1.06 +/- 0.32 s(-1); all P < 0.0001). Accordingly, in HFNEF patients with LV
      mechanical dyssynchrony the rates of LV longitudinal systolic and diastolic
      dysfunction were 64 and 70%, respectively, whereas these rates were significantly
      lower (19.5 and 41.3%), respectively, in patients without asynchronous LV
      contractions. In addition, HFNEF patients with LV mechanical dyssynchrony
      presented higher LV filling pressures and worse NYHA functional class than those
      with normal LV contractions. CONCLUSION: In patients with HFNEF, LV mechanical
      dyssynchrony is associated with an important impairment of the longitudinal
      systolic and diastolic function of the LV. Therefore, the restoration of
      asynchronous LV contractions could help to improve and/or correct both the
      systolic and the diastolic longitudinal dysfunction of the LV in HFNEF and
      thereby improve the symptomatology of these patients.

PMID- 22383373
TI  - Formal synthesis of (-)-cephalotaxine based on a tandem
      hydroamination/semipinacol rearrangement reaction.

PMID- 22383374
TI  - Organic reactions in ionic liquids studied by in situ XPS.
AB  - We demonstrate the application of in situ X-ray photoelectron spectroscopy (XPS)
      to monitor organic, liquid-phase reactions. By covalently attaching ionic head
      groups to the reacting organic molecules, their volatility can be reduced such
      that they withstand ultra high vacuum conditions. The applied method, which is
      new for the investigation of organic reactions, allows for following the fate of
      all elements present in the reaction mixture--except for hydrogen--in a
      quantitative and oxidation-state-sensitive manner in one experiment. This concept
      is demonstrated for the alkylation of a tertiary amine attached to an imidazolium
      or phosphonium moiety by the anion 4-chlorobutylsulfonate ([ClC(4)H(8)SO(3)](-)).
      In the course of the reaction, the covalently bound chlorine is converted to
      chloride and the amine to ammonium as reflected by the distinct shifts in the N
      1s and Cl 2p binding energies.

PMID- 22383371
TI  - Genome integrity, stem cells and hyaluronan.
AB  - Faithful preservation of genome integrity is the critical mission of stem cells
      as well as of germ cells. Reviewed are the following mechanisms involved in
      protecting DNA in these cells: (a) The efflux machinery that can pump out variety
      of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal
      metabolic activity which reduces generation of reactive oxidants, by-products of
      aerobic respiration; (c) the role of hypoxic niche of stem cells providing a
      gradient of variable oxygen tension; (d)(e) the presence of hyaluronan (HA) and
      HA receptors on stem cells and in the niche; (f) the role of role of HA in
      protecting DNA from oxidative damage; (g) the specific role of HA that may play a
      role protecting DNA in stem cells; (h) the interactions of HA with sperm cells
      and oocytes that also may shield their DNA from oxidative damage, and (e)
      mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude
      of functions its anti-oxidant capabilities are often overlooked but may be of
      significance in preservation of integrity of stem and germ cells genome.

PMID- 22383375
TI  - Sex identification of four penguin species using locus-specific PCR.
AB  - Traditional methods for sex identification are not applicable to sexually
      monomorphic species, leading to difficulties in the management of their breeding
      programs. To identify sex in sexually monomorphic birds, molecular methods have
      been established. Two established primer pairs (2550F/2718R and p8/p2) amplify
      the CHD1 gene region from both the Z and W chromosomes. Here, we evaluated the
      use of these primers for sex identification in four sexually monomorphic penguin
      species: king penguins (Aptenodytes patagonicus), rockhopper penguins (Eudyptes
      chrysocome), gentoo penguins (Pygoscelis papua), and Magellanic penguins
      (Spheniscus magellanicus). For all species except rockhopper penguins, primer
      pair 2550F/2718R resulted in two distinct CHD1Z and CHD1W PCR bands, allowing for
      sex identification. For rockhopper penguins, only primer pair p8/p2 yielded
      different CHD1Z and CHD1W bands, which were faint and similar in size making them
      difficult to distinguish. As a result, we designed a new primer pair (PL/PR) that
      efficiently determined the gender of individuals from all four penguin species.
      Sequencing of the PCR products confirmed that they were from the CHD1 gene
      region. Primer pair PL/PR can be evaluated for use in sexing other penguin
      species, which will be crucial for the management of new penguin breeding
      programs.

PMID- 22383376
TI  - Nanoplasmon-enhanced transparent plasma display devices.
AB  - Plasmon-enhanced transparent plasma display devices are demonstrated via the
      resonant interface between Ag nanoparticles and a Eu(3+)-doped phosphor. Enhanced
      emission from the phosphor by metallic nanoparticles leads to an increase of the
      luminous efficacy in the transparent plasma display device. This is a prototype
      of the plasmon-enhanced transparent plasma display device.

PMID- 22383377
TI  - Development of gastric cancer in nonatrophic stomach with highly active
      inflammation identified by serum levels of pepsinogen and Helicobacter pylori
      antibody together with endoscopic rugal hyperplastic gastritis.
AB  - This study aimed to elucidate groups at high risk of developing cancer among
      patients with serologically identified Helicobacter pylori infection and
      nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in
      496 asymptomatic middle-aged men who were H. pylori antibody-positive and
      pepsinogen (PG) test-negative. Subjects were stratified according to the activity
      of H. pylori-associated gastritis measured by serum levels of PG and H. pylori
      antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG),
      and cancer development was investigated. During the study period, seven cases of
      cancer developed in the cohort (incidence rate, 261/100,000 person-years), with
      85.7% developing in the group showing a PGI/II ratio <= 3.0, reflecting active
      inflammation-based high PGII levels. Cancer incidence was significantly higher in
      this group (750/100,000 person-years) than in groups with less active gastritis.
      Furthermore, cancer incidence for this group was significantly higher in the
      subgroup with high H. pylori antibody titers than in the low-titer subgroup.
      Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG
      reflecting localized highly active inflammation, and cancer risk was
      significantly higher in patients with RHG than in patients without. Combining the
      two serum tests and endoscopic examination for RHG allowed identification of
      subjects with more active gastritis and higher cancer risk. No cancer development
      was observed in these high-risk subjects after H. pylori eradication. Subjects
      with highly active gastritis identified by the two serological tests and
      endoscopic RHG constitute a group at high risk of cancer development with H.
      pylori-infected nonatrophic stomach.

PMID- 22383378
TI  - Cyclohexane ring as a tool to select the presentation of the carbohydrate moiety
      in glycosyl amino acids.
AB  - The design of mimic molecules that resemble natural products can be a useful tool
      to help understand the key aspects in molecular recognition processes that are
      difficult to access by using natural derivatives. We present the synthesis and
      the conformational analysis of different glucosylated diamide amino acids that
      simulate glycopeptides with beta-O-linked glucose and contain the nonnatural beta
      hydroxycyclohexane-alpha-amino acid. The study, using NMR experiments, X-ray
      spectroscopy, and molecular dynamics simulations, reveals that the cyclohexane
      ring allows some naturally occurring ways of presentation of the carbohydrate to
      be fixed, or to stabilize some novel conformations. In addition, different chair
      conformations for the cyclohexane-alpha-amino acid moiety can be set, in
      particular, those with high population of conformers in which the bulky groups
      are located at axial positions. Moreover, to increase the scope of these
      cyclohexane derivatives, two dipeptides incorporating the glycomimics have been
      synthesized and further glycosylated to obtain the corresponding alpha-O
      glycopeptides. These features can have important implications for the design of
      new drugs and for understanding the complex molecular processes that take place
      between glycopeptides and their biological targets.

PMID- 22383379
TI  - Screening of metal borohydrides by mechanochemistry and diffraction.

PMID- 22383381
TI  - From ergodicity to extended phase diagrams.
AB  - Structure prediction of stable and metastable phases is put on equal footing for
      the first time, with a solid thermodynamical background. How to estimate the
      lifetime of metastable phases is demonstrated by recent groundbreaking work of
      Jansen, Pentin, and Schon. At the heart lies the exploration of the Gibbs free
      energy landscapes and the extended phase diagrams for complex systems.

PMID- 22383380
TI  - Bidirectional interactions between circadian entrainment and cognitive
      performance.
AB  - Circadian rhythms influence a variety of physiological and behavioral processes;
      however, little is known about how circadian rhythms interact with the organisms'
      ability to acquire and retain information about their environment. These
      experiments tested whether rats trained outside their endogenous active period
      demonstrate the same rate of acquisition, daily performance, and remote memory
      ability as their nocturnally trained counterparts in tasks of sustained attention
      and spatial memory. Furthermore, we explored how daily task training influenced
      circadian patterns of activity. We found that rats demonstrate better acquisition
      and performance on an operant task requiring attentional effort when trained
      during the dark-phase. Time of day did not affect acquisition or performance on
      the Morris water maze; however, when animals were retested 2 wk after their last
      day of training, they showed better remote memory if training originally occurred
      during the dark-phase. Finally, attentional, but not spatial, task performance
      during the light-phase promotes a shift toward diurnality and the synchronization
      of activity to the time of daily training; this shift was most robust when the
      demands on the cognitive control of attention were highest. Our findings support
      a theory of bidirectional interactions between cognitive performance and
      circadian processes and are consistent with the view that the circadian
      abnormalities associated with shift-work, aging, and neuropsychiatric illnesses
      may contribute to the deleterious effects on cognition often present in these
      populations. Furthermore, these findings suggest that time of day should be an
      important consideration for a variety of cognitive tasks principally used in
      psychological and neuroscience research.

PMID- 22383382
TI  - Three-dimensional hierarchically ordered porous carbons with partially graphitic
      nanostructures for electrochemical capacitive energy storage.
AB  - Three-dimensional, hierarchically ordered, porous carbon (HOPC) with designed
      porous textures, serving as an ion-buffering reservoir, an ion-transport channel,
      and a charge-storage material, is expected to be advanced an energy material for
      high-rate supercapacitors. Herein, HOPC without/with partially graphitic
      nanostructures have been directly synthesized by means of a simple one-pot
      synthesis procedure. The designed porous textures of the 3D HOPC materials are
      composed of highly ordered, fcc macroporous (300 nm), interconnected porous
      structures, including macroporous windows (170 nm), hexagonally ordered mesopores
      (5.0 nm), and useful micropores (1.2 nm). 3D HOPC-g-1000 (g=graphitic,
      1000=pyrolysis temperature of 1000  degrees C) with partially graphitic
      nanostructures has a low specific surface area (296 m(2) g(-1)) and a low
      gravimetric specific capacitance (73.4 F g(-1) at 3 mV s(-1)), but improved
      electrical conductivity, better rate performance, higher electrolyte
      accessibility (24.8 MUF cm(-2) at 3 mV s(-1)), faster frequency response (~1 Hz),
      and excellent cycling performance (>5400 cycles). The specific capacitance per
      surface area is higher than that of conventional porous carbons, carbon
      nanotubes, and modified graphene (10-19 MUF cm(-2)).

PMID- 22383383
TI  - Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: operator and
      institutional requirements for transcatheter valve repair and replacement, part
      1: transcatheter aortic valve replacement.

PMID- 22383385
TI  - Sticky bio-inspired micropillars: finding the best shape.
AB  - Very recently, both experimental and theoretical investigations have shown that
      microstructured surfaces covered with mushroom-shaped micropillars present
      strongly enhanced adhesive properties if compared to flat surfaces made of the
      same material. However, different geometries lead to different adhesive
      performance, and finding the optimal solution has become of utmost importance.
      This paper presents on which physical basis the optimal mushroom pillar shape
      should be sought, and it provides a relatively simple methodology to achieve the
      result. Calculations demonstrate that the adhesive performance of the pillar
      strongly depends on the geometry of the terminal plate. The best performance is
      achieved when the ratio s/R(i) between the plate thickness (s) and the pillar
      internal radius (R(i)) is close to 0.2-0.3, and the ratio R(e)/R(i) is larger
      than 2, where R(e) is the external radius of the plate.

PMID- 22383384
TI  - Interaction between the Cockayne syndrome B and p53 proteins: implications for
      aging.
AB  - The CSB protein plays a role in the transcription coupled repair (TCR) branch of
      the nucleotide excision repair pathway. CSB is very often found mutated in
      Cockayne syndrome, a segmental progeroid genetic disease characterized by organ
      degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in
      triggering senescence and apoptosis and suppressing tumorigenesis. Although p53
      is very important to avoid cancer, its excessive activity can be detrimental for
      the lifespan of the organism. This is why a network of positive and negative
      feedback loops, which most likely evolved to fine-tune the activity of this tumor
      suppressor, modulate its induction and activation. Accordingly, an unbalanced p53
      activity gives rise to premature aging or cancer. The physical interaction
      between CSB and p53 proteins has been known for more than a decade but, despite
      several hypotheses, nobody has been able to show the functional consequences of
      this interaction. In this review we resume recent advances towards a more
      comprehensive understanding of the critical role of this interaction in
      modulating p53's levels and activity, therefore helping the system find a
      reasonable equilibrium between the beneficial and the detrimental effects of its
      activity. This crosstalk re-establishes the physiological balance towards cell
      proliferation and survival instead of towards cell death, after stressors of a
      broad nature. Accordingly, cells bearing mutations in the csb gene are unable to
      re-establish this physiological balance and to properly respond to some stress
      stimuli and undergo massive apoptosis.

PMID- 22383386
TI  - Blind estimation of the arterial input function in dynamic contrast-enhanced MRI
      using purity maximization.
AB  - Uncertainty in arterial input function (AIF) estimation is one of the major
      errors in the quantification of dynamic contrast-enhanced MRI. A blind source
      separation algorithm was proposed to determine the AIF by selecting the voxel
      time course with maximum purity, which represents a minimal contamination from
      partial volume effects. Simulations were performed to assess the partial volume
      effect on the purity of AIF, the estimation accuracy of the AIF, and the
      influence of purity on the derived kinetic parameters. In vivo data were acquired
      from six patients with hypopharyngeal cancer and eight rats with brain tumor.
      Results showed that in simulation the AIF with the highest purity is closest to
      the true AIF. In patients, the manually selection had reduced purity, which could
      lead to underestimations of K(trans) and V(e) and an overestimation of V(p) when
      compared with those obtained by the proposed blind source separation algorithm.
      The derived kinetic parameters in the tumor were more susceptible to the changes
      in purity when compared with those in the muscle. The animal experiment
      demonstrated good reproducibility in blind source separation-AIF derived
      parameters. In conclusion, the blind source separation method is feasible and
      reproducible to identify the voxel with the tracer concentration time course
      closest to the true AIF.

PMID- 22383387
TI  - Ultra-rigid metallocenes for highly iso- and regiospecific polymerization of
      propene: the search for the perfect polypropylene helix.

PMID- 22383388
TI  - An airway study of different maxillary and mandibular sagittal positions.

PMID- 22383389
TI  - Dihydropyridones: catalytic asymmetric synthesis, N- to C-sulfonyl transfer, and
      derivatizations.

PMID- 22383390
TI  - Chemistry at the nanoscale: synthesis of an N@C60-N@C60 endohedral fullerene
      dimer.

PMID- 22383391
TI  - Immobilised lipase on structured supports containing covalently attached ionic
      liquids for the continuous synthesis of biodiesel in scCO2.
AB  - Different nanostructured supports, based on 1-decyl-2-methyimidazolium cations
      covalently attached to a polystyrene divinylbenzene porous matrix, were used as
      carriers to immobilise Candida antarctica lipase B. The suitability of these
      immobilised lipase derivatives for the synthesis of biodiesel (methyl oleate) by
      the methanolysis of triolein has been tested in both tert-butanol and
      supercritical (sc)CO(2) (18 MPa, 45  degrees C) as reaction media. The use of
      modified supports with low ionic-liquid loading covalently attached to the main
      polymeric backbone chains provide structured materials that led to the best
      biodiesel yields (up to 95 %) and operational stability (85 % biodiesel yield
      after 45 cycles of 8-4 h) in scCO(2) (45  degrees C, 18 MPa). The presence of
      tert-butanol as an inert cosolvent in the scCO(2) phase at the same concentration
      as triolein was key to avoid poisoning the biocatalyst through the blockage of
      its active sites by the polar byproduct (glycerol) produced in the biodiesel
      synthesis.

PMID- 22383392
TI  - Liquid crystal order in colloidal suspensions of spheroidal particles by direct
      current electric field assembly.
AB  - DC electric fields are used to produce colloidal assemblies with orientational
      and layered positional order from a dilute suspension of spheroidal particles.
      These 3D assemblies, which can be visualized in situ by confocal microscopy, are
      achieved in short time spans (t < 1 h) by the application of a constant voltage
      across the capacitor-like device. This method yields denser and more ordered
      assemblies than had been previously reported with other assembly methods.
      Structures with a high degree of orientational order as well as layered
      positional order normal to the electrode surface are observed. These colloidal
      structures are explained as a consequence of electrophoretic deposition and field
      assisted assembly. The interplay between the deposition rate and the rotational
      Brownian motion is found to be critical for the optimal ordering, which occurs
      when these rates, as quantified by the Peclet number, are of order one. The
      results suggest that the mechanism leading to ordering is equilibrium self
      assembly but with kinetics dramatically accelerated by the application of the DC
      electric field. Finally, the crystalline symmetry of the densest structure formed
      is determined and compared with previously studied spheroidal assemblies.

PMID- 22383393
TI  - Reducing RF-related heating of cardiac pacemaker leads in MRI: implementation and
      experimental verification of practical design changes.
AB  - There are serious concerns regarding safety when performing magnetic resonance
      imaging in patients with implanted conductive medical devices, such as cardiac
      pacemakers, and associated leads, as severe incidents have occurred in the past.
      In this study, several approaches for altering an implant's lead design were
      systematically developed and evaluated to enhance the safety of implanted medical
      devices in a magnetic resonance imaging environment. The individual impact of
      each design change on radiofrequency heating was then systematically investigated
      in functional lead prototypes at 1.5 T. Radiofrequency-induced heating could be
      successfully reduced by three basic changes in conventional pacemaker lead
      design: (1) increasing the lead tip area, (2) increasing the lead conductor
      resistance, and (3) increasing outer lead insulation conductivity. The findings
      show that radiofrequency energy pickup in magnetic resonance imaging can be
      reduced and, therefore, patient safety can be improved with dedicated
      construction changes according to a "safe by design" strategy. Incorporation of
      the described alterations into implantable medical devices such as pacemaker
      leads can be used to help achieve favorable risk-benefit-ratios when performing
      magnetic resonance imaging in the respective patient group.

PMID- 22383394
TI  - Inhibition of p53 expression modifies the specificity of chromatin binding by the
      androgen receptor.
AB  - The androgen receptor (AR) is known to play a critical role in prostate cancer
      (PC). p53 likely also plays a role given that p53 mutations are commonly found in
      advanced PC, and loss of wild-type protein function contributes to the phenotype
      of castration-resistant prostate cancer (CRPC). Nevertheless, the extent of the
      contribution of p53 dysfunction to PC remains unclear. Here we analyze the
      effects of p53 inhibition in PC cells and show that it has significant
      consequences for both the interaction between AR, and chromatin and the
      proliferative capacity of these cells. Inhibition of p53 expression enabled LNCaP
      cells to proliferate independently of androgens. Moreover, it modified the genome
      wide binding pattern of AR. ChIP-sequnce analyis (ChIP-seq) revealed that fewer
      AR-binding sites were present in the context of p53 inhibition, suggesting that
      wild-type p53 is required for stable binding of AR to certain chromatin regions.
      Further analysis revealed that a lower AR occupancy was accompanied by a
      reduction in FoxA1 binding at regulatory regions of AR-dependent genes. Our study
      also identifies a pool of genes that may be transcriptionally regulated by AR
      only in the absence of p53, and that may contribute to the CRPC phenotype.
      Overall, our results point to p53 playing an important role in regulating AR
      activity across the genome.

PMID- 22383395
TI  - Synthesis of aminopyridines and aminopyridones by cobalt-catalyzed [2+2+2]
      cycloadditions involving yne-ynamides: scope, limitations, and mechanistic
      insights.
AB  - An in-depth study of the cobalt-catalyzed [2+2+2] cycloaddition between yne
      ynamides and nitriles to afford aminopyridines has been carried out. About 30
      nitriles exhibiting a broad range of steric demand and electronic properties have
      been evaluated, some of which open new perspectives in metal-catalyzed arene
      formation. In particular, the use of [CpCo(CO)(dmfu)] (dmfu=dimethyl fumarate) as
      a precatalyst made possible the incorporation of electron-deficient nitriles into
      the pyridine core. Modification of the substitution pattern at the yne-ynamide
      allows the regioselectivity to be switched toward 3- or 4-aminopyridines.
      Application of this synthetic methodology to the construction of the
      aminopyridone framework using a yne-ynamide and an isocyanate was also briefly
      examined. DFT computations suggest that 3-aminopyridines are formed by formal
      [4+2] cycloaddition between the nitrile and the intermediate
      cobaltacyclopentadiene, whereas 4-aminopyridines arise from an insertion pathway.

PMID- 22383396
TI  - Type 2 diabetes in pediatrics and adults: thoughts from a clinical pharmacology
      perspective.
AB  - Type 2 diabetes results when insulin secretion is unable to keep the plasma
      glucose levels as per acceptable range. This leads to chronic hyperglycemia and
      its associated microvascular complications such as renal impairment (diabetic
      nephropathy), retinal abnormalities (diabetic retinopathy), and autonomic,
      sensory, and motor neuropathies (diabetic neuropathy) and macrovascular disease.
      Historically, type 2 diabetes is well known as an adult-onset disease; however,
      lately, the incidence of the disease is reported to be increasing in children.
      Despite the wealth of information concerning type 2 diabetes in adults, data
      unique to the pediatric age group regarding the pathophysiology and therapy for
      type 2 diabetes are limited. For treatment in pediatric type 2 diabetes,
      metformin and insulin are the only antidiabetic agents approved currently. There
      are data of use of other oral antidiabetic drugs including glimepiride,
      rosiglitazone, and glyburide (in combination with metformin) in pediatric
      patients; however, formal clinical trials to establish the safety and efficacy
      have not been conducted. This review will compare the clinical pharmacology
      aspects of the oral type 2 diabetic drugs in pediatric and adult populations in
      order to determine any differences between the two patient groups.

PMID- 22383397
TI  - Photoprotection for deltamethrin using chitosan-coated beeswax solid lipid
      nanoparticles.
AB  - BACKGROUND: In the natural environment, photodegradation is one of the most
      common degradative processes of pesticides. In order to reduce the
      photodegradation of pesticides, and so increase their killing activity against
      target pests, chitosan-coated beeswax solid lipid nanoparticles (CH-BSLNs) were
      prepared by a combination of hot homogenization and sonication, with deltamethrin
      as an active ingredient. RESULTS: Under optimal conditions, the highest
      encapsulation efficiency (95%) and a high payload of deltamethrin (approximately
      12.5%) were achieved. In direct photolysis, in the case of CH-BSLNs after UV
      irradiation for 24 h, 37.3% of deltamethrin remained, as opposed to only 14.6% of
      the free-form deltamethrin. In addition, in indirect photolysis, in the case of
      CH-BSLNs after UV irradiation for 2 h in 2% acetone solution, approximately 74.5%
      of deltamethrin remained, as opposed to only 37.6% of the free-form deltamethrin.
      CONCLUSION: CH-BSLNs showed good protection for deltamethrin against
      photodegradation. This novel nanocarrier may be useful in crop protection as an
      economical strategy to enhance the effect of pesticides in the field and protect
      the environment as well.

PMID- 22383398
TI  - Orthogonal riboswitches for tuneable coexpression in bacteria.

PMID- 22383399
TI  - Electrochemically induced maskless metal deposition on micropore wall.
AB  - By applying an external electric field across a micropore via an electrolyte,
      metal ions in the electrolyte can be reduced locally onto the inner wall of the
      micropore, which was fabricated in a silica-covered silicon membrane. This
      maskless metal deposition on the silica surface is a result of the pore membrane
      polarization in the electric field.

PMID- 22383400
TI  - Modulation of mesenchymal stem cell actin organization on conventional
      microcarriers for proliferation and differentiation in stirred bioreactors.
AB  - Tissue engineering applications require an appropriate combination of a cell
      population, biochemical factors and scaffold materials. In this field,
      mesenchymal stem cells (MSCs) emerge as an attractive cell population, due to
      their ready availability and their potential to be differentiated into various
      mesodermal cell types. Commercially available microcarriers have been recently
      recognized as an efficient tool for the propagation of such cells compared to
      traditional monolayer culture, enabling efficient scale-up and serving as a cell
      delivery system. The organization of actin as well as the induction of its
      effectors was previously shown to affect dramatically both proliferation and
      differentiation of MSCs in monolayer culture. To achieve mass scale production of
      differentiated cells derived from MSCs in scalable stirred bioreactors, this work
      aims at rationally screening microcarriers based on the characterization of actin
      organization. First, among the various supports tested, gelatin-based
      microcarriers were found to be most suitable for MSC expansion, due to their best
      adapted actin organization compared to monolayer cultures. Secondly, the proper
      actin organization on Cultispher-S was closely linked to its ability to bind
      serum adhesion molecules enabling Rho GTPase activation. Finally, by modulating
      actin behaviour, it was feasible to efficiently guide MSC differentiation on
      microcarriers. Taken together, these results show that controlling actin
      behaviour is a good strategy toward mass scale sequential expansion followed by
      differentiation of MSCs in a microcarrier based bioreactor.

PMID- 22383401
TI  - Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle
      in an orthotopic mouse model of human brain tumors.
AB  - It has been hypothesized that increased flux through the pentose phosphate
      pathway (PPP) is required to support the metabolic demands of rapid malignant
      cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal
      cell carcinoma metastatic to brain, we estimated the activity of the PPP relative
      to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3
      (13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and
      their respective surrounding brains (GBM, 0.197 +/- 0.011 and 0.195 +/- 0.033,
      respectively (p = 1); metastasis: 0.126 and 0.119 +/- 0.033, respectively). This
      suggests that the rate of glycolysis is significantly greater than the PPP flux
      in these tumors, and that the PPP flux into the lactate pool is similar in both
      tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from
      Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the
      renal cell carcinoma, in contrast with GBM, (13) C multiplets of gamma
      aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that
      GABA did not derive from a common glutamate precursor pool. In addition, the
      orthotopic renal tumor, the patient's primary renal mass and brain metastasis
      were all strongly immunopositive for the 67-kDa isoform of glutamate
      decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray
      of the same histology, suggesting that GABA synthesis is cell autonomous in at
      least a subset of renal cell carcinomas. Taken together, these data demonstrate
      that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor
      metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis
      and therapy.

PMID- 22383403
TI  - Quantification of pulmonary microcirculation by dynamic contrast-enhanced
      magnetic resonance imaging: comparison of four regularization methods.
AB  - Tissue microcirculation can be quantified by a deconvolution analysis of
      concentration-time curves measured by dynamic contrast-enhanced magnetic
      resonance imaging. However, deconvolution is an ill-posed problem, which requires
      regularization of the solutions. In this work, four algebraic
      deconvolution/regularization methods were evaluated: truncated singular value
      decomposition and generalized Tikhonov regularization (GTR) in combination with
      the L-curve criterion, a modified LCC (GTR-MLCC), and a response function model
      that takes a-priori knowledge into account. To this end, dynamic contrast
      enhanced magnetic resonance imaging data sets were simulated by an established
      physiologically reference model for different signal-to-noise ratios and measured
      on a 1.5-T system in the lung of 10 healthy volunteers and 20 patients. Analysis
      of both the simulated and measured dynamic contrast-enhanced magnetic resonance
      imaging datasets revealed that GTR in combination with the L-curve criterion does
      not yield reliable and clinically useful results. The three other
      deconvolution/regularization algorithms resulted in almost identical
      microcirculatory parameter estimates for signal-to-noise ratios > 10. At low
      signal-to-noise ratios levels (<10) typically occurring in pathological lung
      regions, GTR in combination with a modified L-curve criterion approximates the
      true response function much more accurately than truncated singular value
      decomposition and GTR in combination with response function model with a
      difference in accuracy of up to 76%. In conclusion, GTR in combination with a
      modified L-curve criterion is recommended for the deconvolution of dynamic
      contrast-enhanced magnetic resonance imaging curves measured in the lung
      parenchyma of patients with highly heterogeneous signal-to-noise ratios.

PMID- 22383402
TI  - Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene
      EWS-FLI1.
AB  - Oncogenic fusion proteins, such as EWS-FLI1, are excellent therapeutic targets as
      they are only located within the tumor. However, there are currently no agents
      targeted toward transcription factors, which are often considered to be
      'undruggable.'  A considerable body of evidence is accruing that refutes this
      claim based upon the intrinsic disorder of transcription factors.  Our previous
      studies show that RNA Helicase A (RHA) enhances the oncogenesis of EWS-FLI1, a
      putative intrinsically disordered protein.  Interruption of this protein-protein
      complex by small molecule inhibitors validates this interaction as a unique
      therapeutic target.  Single enantiomer activity from a chiral compound has been
      recognized as strong evidence for specificity in a small molecule-protein
      interaction.  Our compound, YK-4-279, has a chiral center and can be separated
      into two enantiomers by chiral HPLC.  We show that there is a significant
      difference in activity between the two enantiomers.  (S)-YK-4-279 is able to
      disrupt binding between EWS-FLI1 and RHA in an immunoprecipitation assay and
      blocks the transcriptional activity of EWS-FLI1, while (R)-YK-4-279 cannot. 
      Enantiospecific effects are also established in cytotoxicity assays and caspase
      assays, where up to a log-fold difference is seen between (S)-YK-4-279 and the
      racemic YK-4-279.  Our findings indicate that only one enantiomer of our small
      molecule is able to specifically target a protein-protein interaction. This work
      is significant for its identification of a single enantiomer effect upon a
      protein interaction suggesting that small molecule targeting of intrinsically
      disordered proteins can be specific. Furthermore, proving YK-4-279 has only one
      functional enantiomer will be helpful in moving this compound towards clinical
      trials.

PMID- 22383404
TI  - Internet-based course on pulmonary pathophysiology.
AB  - A course of seven video lectures on pulmonary pathophysiology has been placed on
      the internet. This is a companion to the course on respiratory physiology
      available at http://meded.ucsd.edu/ifp/jwest/. That course dealt with normal
      respiratory physiology, and the new lectures are about the function of the
      diseased lung. The topics covered include pulmonary function tests, chronic
      obstructive pulmonary disease, asthma and localized airway obstruction,
      restrictive lung diseases, pulmonary vascular diseases, environmental or
      industrial lung diseases (with a short section on neoplastic and infectious
      diseases), and respiratory failure. Although it could be argued that PhD
      physiologists do not have a responsibility for teaching pathophysiology,
      collaborative teaching has become increasingly common in medical schools where,
      for example, a pulmonary block includes both normal respiratory physiology and
      some pulmonary pathophysiology. It is hoped that these lectures will be useful to
      physiologists in that setting.

PMID- 22383405
TI  - Different tests for a difference: how do we do research?

PMID- 22383406
TI  - Effect of uniform versus expanding retrieval practice on the recall of physiology
      information.
AB  - The purpose of this study was to compare the retention of selected physiology
      concepts throughout 30 days of two different uniform schedules of retrieval and
      two different expanding schedules of retrieval. Participants (n = 250) first read
      and reread 30 immunology and reproductive physiology concepts and were then
      repeatedly assessed, without feedback, according to one of the following four
      randomly assigned schedules: 1) immediately after learning and again 9 and 19
      days later [uniform (days 1, 10, and 20)]; 2) 7, 14, and 21 days after learning
      [uniform (days 8, 15, and 22)]; 3) immediately after learning and again 5 and 15
      days later [expanding (days 1, 6, and 16)]; and 4) 1, 6, and 16 days after
      learning [expanding (days 2, 7, and 17)]. All participants completed a final
      assessment 29 days after learning the physiology concepts. Mean final assessment
      scores +/- SE for the uniform (days 1, 10, and 20), uniform (days 8, 15, and 22),
      expanding (days 1, 6, and 16), and expanding (days 2, 7, and 17) groups were
      36.15 +/- 1.97, 32.31 +/- 1.87, 45.80 +/- 2.56, and 39.71 +/- 2.48, respectively.
      There were no differences in final assessment scores between the two expanding
      retrieval groups, but expanding (days 1, 6, and 16) group scores were
      significantly higher than those in both uniform retrieval groups (ANOVA, F =
      6.52, P = 0.00). Also, the combined mean of the two expanding retrieval
      conditions (42.57 +/- 1.80) was significantly higher (F = 14.09, P = 0.00) than
      the combined mean of the two uniform retrieval conditions (34.10 +/- 1.36). The
      results indicate that participants benefited more from expanding retrieval
      practice, particularly when the first assessment was administered immediately
      after learning.

PMID- 22383407
TI  - The UNSIN project: exploring the molecular physiology of sins.
AB  - Although active learning works, promoting it in large undergraduate science
      classes is difficult. Here, three students (F. Naji, L. Salci, and G. Hoit) join
      their teacher (P. K. Rangachari) in describing one such attempt. Two cohorts in a
      first-year undergraduate biology course explored the molecular underpinnings of
      human misbehavior. Students were divided into 18 groups and randomly allotted to
      deal with one of the four deadly sins: sloth, gluttony, lust, and wrath. Students
      were expected to read primary sources to devise molecular ways to counter these
      sins. Group progress was monitored over the 12-wk period by the preceptor (P. K.
      Rangachari) at scheduled intervals. A single randomly selected student was
      questioned about the work done, and future directions were provided by the
      preceptor. At the end of the term, randomly selected students defended their
      group's approaches to the entire class. A final written report was graded. The
      following multiple target molecules were considered for each sin: gluttony
      (cholecystokinin, ghrelin, GABA, leptin, peptide YY, neuropeptide Y, and the
      melanocortin 4 receptor); sloth (dopamine, glutamate, GABA, and orexin); wrath
      (serotonin, GABA, glutamate, and corticotropin-releasing hormone receptor 2); and
      lust (prolactin, testosterone, oxytocin, dopamine, and estrogen). Students noted
      that the project provided a valuable learning experience, and the random
      selection approach gave students a greater sense of responsibility to their
      group. The project helped students hone their skills at searching, synthesizing,
      sharing, and presenting information, fostered group interactions, and provided a
      solid knowledge base for subsequent courses.

PMID- 22383408
TI  - Continuous and noninvasive recording of cardiovascular parameters with the
      Finapres finger cuff enhances undergraduate student understanding of physiology.
AB  - The Finapres finger cuff recording system provides continuous calculations of
      beat-to-beat variations in cardiac output (CO), total peripheral resistance,
      heart rate (HR), and blood pressure (BP). This system is unique in that it allows
      experimental subjects to immediately, continuously, and noninvasively visualize
      changes in CO at rest and during exercise. This study provides evidence that
      using the Finapres system improves undergraduate student engagement,
      understanding, and learning of how the cardiovascular system responds to
      exercise. Second-year science students undertaking a physiology practical class
      in 2009 (n = 243) and 2010 (n = 263) used the Finapres system to record CO, BP,
      and HR during graded exercise on a cycle ergometer. Student experiences with the
      Finapres was evaluated with a survey (a 5-point scale from strongly disagree to
      strongly agree). This indicated that students appreciated the immediacy of the
      recordings (88% of students agreed or strongly agreed, average for 2009 and
      2010), gained an understanding of how to record physiological data (84%), enjoyed
      the practical (81%), and would recommend the Finapres to other students (81%). To
      determine if the practical enhanced student learning of cardiovascular
      physiology, identical tests were given to the students at the beginning (pretest)
      and end (posttest) of the class. There was a significant improvement from the
      pretest to the posttest (4% in 2009 and 20% in 2010). In summary, the ability of
      the Finapres to continuously display CO, BP, and HR during experimental protocols
      provides students with immediate feedback and improves their understanding of
      cardiovascular physiology.

PMID- 22383409
TI  - An international basic science and clinical research summer program for medical
      students.
AB  - An important part of training the next generation of physicians is ensuring that
      they are exposed to the integral role that research plays in improving medical
      treatment. However, medical students often do not have sufficient time to be
      trained to carry out any projects in biomedical and clinical research. Many
      medical students also fail to understand and grasp translational research as an
      important concept today. In addition, since medical training is often an
      international affair whereby a medical student/resident/fellow will likely train
      in many different countries during his/her early training years, it is important
      to provide a learning environment whereby a young medical student experiences the
      unique challenges and value of an international educational experience. This
      article describes a program that bridges the gap between the basic and clinical
      research concepts in a unique international educational experience. After
      completing two semester curricula at Alfaisal University in Riyadh, Kingdom of
      Saudi Arabia, six medical students undertook a summer program at St. Boniface
      Hospital Research Centre, in Winnipeg, MB, Canada. The program lasted for 2 mo
      and addressed advanced training in basic science research topics in medicine such
      as cell isolation, functional assessment, and molecular techniques of analysis
      and manipulation as well as sessions on the conduct of clinical research trials,
      ethics, and intellectual property management. Programs such as these are
      essential to provide a base from which medical students can decide if research is
      an attractive career choice for them during their clinical practice in subsequent
      years. An innovative international summer research course for medical students is
      necessary to cater to the needs of the medical students in the 21st century.

PMID- 22383410
TI  - Emergency contraception and RU-486 (mifepristone): do bioethical discussions
      improve learning and retention?
AB  - To systematically investigate whether the inclusion of a bioethical discussion
      improves the learning and retention of biological content, students in two
      sections of an introductory zoology class were taught the biology behind
      emergency contraception and RU-486. Students in one section of the course
      participated in a bioethical discussion, whereas students in the other section
      participated in a content-only discussion. Pre- and postsurveys, response
      paragraphs, and a final exam were collected and used to examine the learning and
      retention of content knowledge. Results suggested that students who participated
      in a bioethical discussion of emergency contraception and RU-486 learned and
      retained information better than students who received content-only instruction.
      Interestingly, students who participated in the bioethical discussion also
      appeared to be more confident in their answers. The results of this study may
      inform the teaching practices and goals of science educators who would like to
      incorporate a discussion of bioethical issues into their curriculum but often
      feel that content coverage is paramount.

PMID- 22383411
TI  - Effects of different forms of physiology instruction on the development of
      students' conceptions of and approaches to science learning.
AB  - The purpose of this study was to investigate students' conceptions of and
      approaches to learning science in two different forms: internet-assisted
      instruction and traditional (face-to-face only) instruction. The participants who
      took part in the study were 79 college students enrolled in a physiology class in
      north Taiwan. In all, 46 of the participants were from one class and 33 were from
      another class. Using a quasi-experimental research approach, the class of 46
      students was assigned to be the "internet-assisted instruction group," whereas
      the class of 33 students was assigned to be the "traditional instruction group."
      The treatment consisted of a series of online inquiry activities. To explore the
      effects of different forms of instruction on students' conceptions of and
      approaches to learning science, two questionnaires were administered before and
      after the instruction: the Conceptions of Learning Science Questionnaire and the
      Approaches to Learning Science Questionnaire. Analysis of covariance results
      revealed that the students in the internet-assisted instruction group showed less
      agreement than the traditional instruction group in the less advanced conceptions
      of learning science (such as learning as memorizing and testing). In addition,
      the internet-assisted instruction group displayed significantly more agreement
      than the traditional instruction group in more sophisticated conceptions (such as
      learning as seeing in a new way). Moreover, the internet-assisted instruction
      group expressed more orientation toward the approaches of deep motive and deep
      strategy than the traditional instruction group. However, the students in the
      internet-assisted instruction group also showed more surface motive than the
      traditional instruction group did.

PMID- 22383413
TI  - Analytical essay writing: a new activity introduced to a traditional curriculum.
AB  - Medical students following a traditional curriculum get few opportunities to
      engage in activities such as a literature search, scientific writing, and active
      and collaborative learning. An analytical essay writing activity (AEWA) in
      physiology was introduced to first-year students. Each student prepared an essay
      incorporating new research findings with existing knowledge on a medical topic.
      Students were expected to study on the topic in detail from textbooks as well as
      from research publications and write a descriptive and critical analysis. This
      activity would help them to be aware of new developments in the field and
      understand the complexity and rapidity of changes in the subject. The aim of this
      study was to learn how students used the AEWA as a learning process. For this
      purpose, student perceptions were assessed quantitatively and those of the
      faculty staff were assessed qualitatively. The data from the students showed
      considerable achievements in the medical database search, scientific writing,
      group work, and search for new scientific knowledge. The activity was influenced
      by prior capabilities in computer use, English language knowledge, and writing
      ability. Resources available at the medical school had a greater influence on the
      activity. Faculty staff appreciated the quality of the essay while highlighting
      areas of improvement. The students seemed to be satisfied with the supervisory
      role of the faculty staff, whereas the staff felt that the students used the
      supervisors less than expected. The AEWA was a successful activity promoting many
      aspects of active and collaborative learning. The low availability of books and
      information and communications technology (ICT) resources, poor internet
      connection, and insufficient English language skills were probably responsible
      for the negative feedback on this activity in this resource-deprived environment.

PMID- 22383412
TI  - The use of virtual patients in medical school curricula.
AB  - The demonstration of patient-based cases using automated technology [virtual
      patients (VPs)] has been available to health science educators for a number of
      decades. Despite the promise of VPs as an easily accessible and moldable
      platform, their widespread acceptance and integration into medical curricula have
      been slow. Here, the authors review the technological underpinnings of VPs,
      summarize the literature regarding the use and limitations of VPs in the
      healthcare curriculum, describe novel possible applications of the technology,
      and propose possible directions for future work.

PMID- 22383414
TI  - A laboratory exercise using a physical model for demonstrating countercurrent
      heat exchange.
AB  - A physical model was used in a laboratory exercise to teach students about
      countercurrent exchange mechanisms. Countercurrent exchange is the transport of
      heat or chemicals between fluids moving in opposite directions separated by a
      permeable barrier (such as blood within adjacent blood vessels flowing in
      opposite directions). Greater exchange of heat or chemicals between the fluids
      occurs when the flows are in opposite directions (countercurrent) than in the
      same direction (concurrent). When a vessel loops back on itself, countercurrent
      exchange can occur between the two arms of the loop, minimizing loss or uptake at
      the bend of the loop. Comprehension of the physical principles underlying
      countercurrent exchange helps students to understand how kidneys work and how
      modifications of a circulatory system can influence the movement of heat or
      chemicals to promote or minimize exchange and reinforces the concept that heat
      and chemicals move down their temperature or concentration gradients,
      respectively. One example of a well-documented countercurrent exchanger is the
      close arrangement of veins and arteries inside bird legs; therefore, the setup
      was arranged to mimic blood vessels inside a bird leg, using water flowing inside
      tubing as a physical proxy for blood flow within blood vessels.

PMID- 22383415
TI  - Classic experimentation and working models for engaging and inspiring students.

PMID- 22383416
TI  - The insulation bag: learning thermoregulation through a "hands-in" activity.

PMID- 22383417
TI  - Literature and science: a different look inside neurodegeneration.

PMID- 22383418
TI  - Training scientists in a science center improves science communication to the
      public.

PMID- 22383419
TI  - Non-target-site-based resistance to ALS-inhibiting herbicides in six Bromus
      rigidus populations from Western Australian cropping fields.
AB  - BACKGROUND: Bromus rigidus is a common weed species that has increased in
      cropping fields owing to limited control options. During a random field survey in
      Western Australia, six B. rigidus populations that had survived in-crop weed
      control programmes were collected. The study aimed to determine the resistance
      profile of these six populations. RESULTS: Based on dose-response studies, all
      six B. rigidus populations had a low-level resistance to sulfosulfuron and
      sulfometuron (both sulfonylurea herbicides) while remaining susceptible to
      herbicides with other modes of action. ALS in vitro activity assays revealed no
      differences in enzyme sensitivity between susceptible and resistant populations,
      while the use of malathion (a cytochrome P450 inhibitor) in combination with
      sulfosulfuron caused the resistant populations to behave like the susceptible
      population. CONCLUSION: This study established that these six B. rigidus
      populations have a low-level resistance to the ALS-inhibiting sulfonylurea
      herbicides, but are able to be controlled by other herbicide modes of action. The
      low-level, malathion-reversible resistance, together with a sensitive ALS,
      strongly suggest that a non-target-site enhanced metabolism is the mechanism of
      resistance.

PMID- 22383420
TI  - Cell adhesion behavior on enantiomerically functionalized zeolite L monolayers.

PMID- 22383421
TI  - Derivatization followed by gas chromatography-mass spectrometry for
      quantification of ethyl carbamate in alcoholic beverages.
AB  - A sensitive and rapid analytical methodology based on derivatization followed by
      gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative
      determination of the toxic contaminant ethyl carbamate (EC, urethane,
      C(2)H(5)OCONH(2)) in alcoholic samples. EC was extracted using liquid-liquid
      extraction technique, and then silylated with bis
      (trimethylsilyl)trifluoroacetamide, analysed finally by GC-MS. The isopropyl
      carbamate was used as the internal standard for quantitative analysis of EC in
      alcoholic samples. In this work, the sample extraction and derivatization
      reaction conditions were investigated, and the optimal extraction conditions
      obtained were: pH 9 and solvent of ethyl acetate, and the derivatization
      conditions were: derivatization reaction temperature of 80 degrees C and time
      duration of 30 min. With the optimal conditions, the method validations were also
      studied. In the validation studies, EC exhibited good linearity with a regression
      coefficient of 0.9999. The limit of detection and limit of quantification were
      0.30 and 5.0 MUg/kg, respectively. The precision was less than 8.4%. Finally, the
      proposed technique was successfully applied to the analysis of EC in 35 kinds of
      alcoholic samples. The experimental results have demonstrated that the proposed
      technique is a fast, reliable and low-cost method for determination of EC in
      alcoholic samples.

PMID- 22383422
TI  - Seasonal morphological variations and age-related changes of the seminal vesicle
      of viscacha (Lagostomus maximus maximus): an ultrastructural and
      immunohistochemical study.
AB  - The viscacha is a seasonal rodent that exhibit an annual reproductive cycle with
      periods of maximum reproductive activity and gonadal regression. We studied
      seasonal variations in the morphology and cellular population of the seminal
      vesicles (SVs) during both periods and in impuber animals. Seminal vesicles were
      studied by light and electronic microscopy. Measurements of epithelial height,
      nuclear diameter, luminal diameter, and muscular layer were performed. Also, we
      studied the distribution of androgen receptors (AR) in this gland during the
      reproductive cycle and in impuber animal. During gonadal regression, principal
      and clear cells showed signs of reduced functional activity. These were
      characterized by an epithelium of smaller height, irregular nuclei, and cytoplasm
      with few organelles, dilated cisterns, and glycogen granules. In impuber animals,
      the principal cells showed large nuclei with chromatin lax and cytoplasm with
      small mitochondria, poorly developed Golgi apparatus, and granules of glycogen.
      On the other hand, the cells exhibited seasonal variations in the distribution
      and percentage of immunolabeled cells to AR throughout the annual reproductive
      cycle. During the gonadal regression period, glandular mucosa exhibited numerous
      epithelial cells with intense nuclear staining. However, fibromuscular stromal
      cells were weakly positive for AR in contrast to what was observed during the
      activity period. Considering that testosterone values are lower in adult animals
      during the period of gonadal regression and in impuber animals, our
      immunohistochemical results show a significant correlation with the percentage of
      AR-immunopositive cells. In conclusion, these results demonstrate that the
      structure of the SVs changes in the activity period of viscacha, probably because
      of elevated levels of testosterone leading to an increase in the secretory
      activity of epithelial cells.

PMID- 22383423
TI  - Expanding the scope of anatomical sciences: the case of "Human evolution: The
      fossil evidence" course at the Sackler School of Medicine, Tel-Aviv University.
AB  - The Anatomy Department at Tel-Aviv University Medical School offers its students
      an elective course of 26 didactic hours on human evolution. The course is open to
      students from all faculties, who must fulfill all academic requirements, without
      a prerequisite of a background in anatomy. Approximately 120 students attend
      annually, a third of them are nonmedical students who major in philosophy,
      archeology, and sociology. This article discusses the course's contributions to
      students' understanding of a scientific concept that a scientific theory can be
      contradicted by new evidence, because facts govern science. Also, research
      methods of applying scientific principles establish the understanding of the
      human body, which evidently contributes to health and medicine. In the classes,
      the students are divided into mini-groups of 2-3 students, while the lecturer
      moves among students to examine fossils. In addition, analogies, open
      discussions, and explanations accompany the tangible experiences. The lecturer of
      the course is an experienced anthropologist-anatomist researcher. He is a role
      model and a mentor, sharing with the students his belief that a scientist should
      be persistent in his research to overcome difficult circumstances. Students,
      regardless of their backgrounds, express high appreciation of the course in their
      feedback questionnaires. The message conveyed by this course is that not only
      knowledge counts but also its integration with scientific principles. This course
      teaches us that science can bring students from different areas to study together
      and share ideas. In conclusion, this is a unique course in the eyes of the
      faculty and students alike.

PMID- 22383424
TI  - Distal pocket control of nitrite binding in myoglobin.

PMID- 22383426
TI  - Genome-wide gene expression profiling identifies overlap with malignant
      adrenocortical tumours and novel mechanisms of inefficient steroidogenesis in
      familial ACTH-independent macronodular adrenal hyperplasia.

PMID- 22383428
TI  - Vitamin D and colon cancer.
AB  - The most active vitamin D metabolite, 1alpha,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)), is a pleiotropic hormone with wide regulatory actions.
      Classically, vitamin D deficiency was known to alter calcium and phosphate
      metabolism and bone biology. In addition, recent epidemiological and experimental
      studies support the association of vitamin D deficiency with a large variety of
      human diseases, and particularly with the high risk of colorectal cancer. By
      regulating the expression of many genes via several mechanisms, 1,25(OH)(2)D(3)
      induces differentiation, controls the detoxification metabolism and cell
      phenotype, sensitises cells to apoptosis and inhibits the proliferation of
      cultured human colon carcinoma cells. Consistently, 1,25(OH)(2)D(3) and several
      of its analogues decrease intestinal tumourigenesis in animal models. Molecular,
      genetic and clinical data in humans are scarce but they suggest that vitamin D is
      protective against colon cancer. Clearly, the available evidence warrants new,
      well-designed, large-scale trials to clarify the role of vitamin D in the
      prevention and/or therapy of this important neoplasia.

PMID- 22383427
TI  - Sorafenib decreases proliferation and induces apoptosis of prostate cancer cells
      by inhibition of the androgen receptor and Akt signaling pathways.
AB  - Antihormonal and chemotherapy are standard treatments for nonorgan-confined
      prostate cancer. The effectivity of these therapies is limited and the
      development of alternative approaches is necessary. In the present study, we
      report on the use of the multikinase inhibitor sorafenib in a panel of prostate
      cancer cell lines and their derivatives which mimic endocrine and chemotherapy
      resistance. (3)H-thymidine incorporation assays revealed that sorafenib causes a
      dose-dependent inhibition of proliferation of all cell lines associated with
      downregulation of cyclin-dependent kinase 2 and cyclin D1 expression. Apoptosis
      was induced at 2  MUM of sorafenib in androgen-sensitive cells, whereas a higher
      dose of the drug was needed in castration-resistant cell lines. Sorafenib
      stimulated apoptosis in prostate cancer cell lines through downregulation of
      myeloid cell leukemia-1 (MCL-1) expression and Akt phosphorylation. Although
      concentrations of sorafenib required for the antitumor effect in therapy
      resistant sublines were higher than those needed in parental cells, the drug
      showed efficacy in cells which became resistant to bicalutamide and docetaxel
      respectively. Most interestingly, we show that sorafenib has an inhibitory effect
      on androgen receptor (AR) and prostate-specific antigen expression. In cells in
      which AR expression was downregulated by short interfering RNA, the treatment
      with sorafenib increased apoptosis in an additive manner. In summary, the results
      of the present study indicate that there is a potential to use sorafenib in
      prostate cancers as an adjuvant therapy option to current androgen ablation
      treatments, but also in progressed prostate cancers that become unresponsive to
      standard therapies.

PMID- 22383429
TI  - Synthesis and structure elucidation of five new conjugates of oleanolic acid
      derivatives and chalcones using 1D and 2D NMR spectroscopy.
AB  - Five new conjugates of oleanolic acid derivatives and chalcones have been
      designed and synthesized. The structure elucidation of these conjugates was
      accomplished by using extensive 1D ((1)H, (13)C) and 2D NMR spectroscopic studies
      (COSY, HSQC and HMBC); and alpha-glucosidase inhibitory activity is reported for
      these conjugates. Compound 2b (IC(50)  = 47.5 um) displayed much stronger
      activity than oleanolic acid and acarbose.

PMID- 22383430
TI  - Nonlinear behavior of three-terminal graphene junctions at room temperature.
AB  - We demonstrate nonlinear behavior in three-terminal T-branch graphene devices at
      room temperature. A rectified nonlinear output at the center branch is observed
      when the device is biased by a push-pull configuration. Nonlinearity is assumed
      to arise from a difference in charge transfer through the metal-graphene contact
      barrier between two contacts. The sign of the rectification can be altered by
      changing the carrier type using the back-gate voltage.

PMID- 22383431
TI  - Direct conversion of methane into formaldehyde mediated by [Al2O3]+ at room
      temperature.

PMID- 22383432
TI  - The structure of glibenclamide in the solid state.
AB  - The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino)carbonyl]
      aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug,
      has been studied both in solution and in the solid state by a combination of NMR
      spectroscopy and theoretical calculations. The possibility that glibenclamide
      suffers a tautomerization under melting to afford a desmotrope was rejected.

PMID- 22383433
TI  - Single-step formation of a graphene-metal hybrid transparent and electrically
      conductive film.
AB  - We report here a rapid (10 s of heating) graphene growth method that can be
      carried out on any desired substrate, including an insulator, thus negating the
      need for the transfer from the metal substrate. This technique is based on metal
      induced crystallization of amorphous carbon (a-C) to graphene, and involves an
      ultra-thin metal layer that is less than 10 nm in thickness. Rapid annealing of a
      bilayer of a-C and metal deposited on the surface leads to the formation of
      graphene film, and to subsequent breaking-up of the thin metal layer underneath
      the film, thus resulting in the formation of a graphene-metal hybrid film which
      is both transparent and electrically conducting. Based on Raman studies, we have
      also systematically compared ultra-thin metal-induced crystallization behavior
      with a case of conventional thick metal. Based on the present investigation, it
      was observed that the dominant growth mechanism in ultra-thin metal-induced
      crystallization is nucleation controlled.

PMID- 22383434
TI  - Gilbert Stork: in his own words and in the musings of his friends.

PMID- 22383435
TI  - FTY720 on the way from the base camp to the summit of the mountain: relevance for
      remyelination.
AB  - FTY720 (fingolimod; Gilenya(r)), a sphingosine 1-phosphate (S1P) receptor
      modulator, is the first oral disease-modifying therapy to be approved for the
      treatment of relapsing-remitting multiple sclerosis. FTY720 is rapidly converted
      in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This
      action inhibits egress of lymphocytes from the lymph nodes, preventing entry into
      the blood and thus infiltration into the central nervous system. More recent
      studies, however, convincingly show that FTY720 crosses the blood-brain barrier,
      where it is thought to act on S1P receptors on cells within the central nervous
      system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the
      evidence showing that FTY720 also plays a role in remyelination and repair within
      the brain. While the mechanisms of action still require firm elucidation, it is
      clear that FTY720 could also be reparative, extending its therapeutic potential
      for multiple sclerosis.

PMID- 22383436
TI  - In assessing multiple sclerosis disease activity patient report measures are a
      waste of time: cut to the MRI scan!--Yes.

PMID- 22383437
TI  - In assessing multiple sclerosis disease activity patient report measures are a
      waste of time: cut to the MRI scan!--No.

PMID- 22383438
TI  - In assessing multiple sclerosis disease activity patient report measures are a
      waste of time: cut to the MRI scan!--Commentary.

PMID- 22383439
TI  - NMR spectroscopic investigation of inclusion complexes between cyclodextrins and
      the neurotoxin tetramethylenedisulfotetramine.
AB  - The binding stoichiometry, strength and structure of inclusion complexes formed
      between the neurotoxin tetramethylenedisulfotetramine (TETS) and both native and
      modified cyclodextrins (CyDs) were investigated using nuclear magnetic resonance
      (NMR) spectroscopy. Of all six examined cases, native beta-cyclodextrin (beta
      CyD) and its chemically modified counterpart heptakis-(2,3,6-tris-(2
      hydroxypropyl))-beta-cyclodextrin (2HP-beta-CyD) were found to associate most
      strongly with TETS as reflected in the magnitude of their binding constants (K =
      537 +/- 26 M(-1) for beta-CyD and K = 514 +/- 49 M(-1) for 2HP-beta-CyD). Two
      dimensional rotating-frame Overhauser effect spectroscopy NMR experiments confirm
      close proximity of the TETS molecule to both beta-CyD and 2HP-beta-CyD as
      intermolecular, through-space interactions between the H3 and H5 protons located
      in the interior of the CyD cavity and the methylene protons of TETS were
      identified.

PMID- 22383440
TI  - Catheter-associated bloodstream infection caused by Leifsonia aquatica in a
      haemodialysis patient: a case report.
AB  - Leifsonia aquatica is an aquatic coryneform rod that is capable of forming
      biofilms in environmental water sources. It has rarely been associated with human
      infections and its pathogenicity and clinical significance are uncertain. We
      describe a case of catheter-related bloodstream infection in a haemodialysis
      patient. The isolate grew on conventional media as a yellow-pigmented colony, but
      identification required molecular methods. Although the strain displayed reduced
      sensitivity to vancomycin, the clinical outcome was favourable after catheter
      removal and intravenous treatment with this antibiotic. Our report gives further
      evidence of the capability of this aquatic bacterium to cause human infection.

PMID- 22383441
TI  - Use of a new screening medium to detect carbapenem-non-susceptible members of the
      Enterobacteriaceae.

PMID- 22383442
TI  - Abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in Spain.
AB  - We describe a clinical case of an abdominal abscess due to NDM-1-producing
      Klebsiella pneumoniae in a 35-year-old Spanish patient after hospitalization in
      India for perforated appendicitis and peritonitis. The strain belonged to the
      MLST type 231 and had multiple additional antibiotic resistance genes such as
      bla(CTX-M-15), armA methylase, aac(6')-Ib-cr, dfrA12, sul1 and qnrB and lack of
      porin genes ompK35 and ompK36. The patient was cured after abscess drainage.

PMID- 22383443
TI  - Diarrhoeagenic Escherichia coli as a predominant cause of paediatric nosocomial
      diarrhoea in India.
AB  - Intestinal nosocomial infections remain a major concern in paediatric wards
      leading to increased morbidity and mortality. This study determined the
      aetiological and epidemiological profile of nosocomial diarrhoea (ND) among
      children admitted to a hospital in India. During the period of January 2008 to
      June 2009, we consecutively enrolled 100 children between the age of 2 months and
      14 years who developed ND as defined by the Centers for Disease Control and
      Prevention. A control group of patients matched for age and severity score but
      with no diarrhoea at admission or during their hospital stay (n=50) were also
      enrolled. Stool samples were cultured for various pathogens using standard
      protocols. Clostridium difficile toxins and rotavirus antigen were detected using
      commercial ELISAs. Detection of diarrhoeagenic Escherichia coli was carried out
      by multiplex PCR assay. All patient details were noted. In this study, males
      predominated (77%), and 56% children were <1 year of age and 96% were <5 years.
      The mean duration of diarrhoea and hospitalization in the case group was 3.2 days
      and 27.5 days, respectively. Malignancy and nasogastric tube usage were
      significant underlying factors for the development of ND. Diarrhoeagenic E. coli
      was the commonest agent (47%: enterotoxigenic E. coli, enteroaggregative E. coli
      and enteropathogenic E. coli were isolated in 22, 18 and 7% of patients,
      respectively). C. difficile toxin was seen in 9% of cases, whilst rotavirus was
      found in 8% of cases. Although rotavirus and C. difficile are major causative
      agents of hospital-acquired diarrhoea in the developed world, in this setting
      diarrhoeagenic E. coli was responsible for the majority of cases of hospital
      acquired diarrhoea. ND was most common in children aged <5 years.

PMID- 22383444
TI  - Detection of carbapenemase-producing Enterobacteriaceae with a commercial DNA
      microarray.
AB  - The Check-MDR CT102 DNA microarray enables detection of the most prevalent
      carbapenemases (NDM, VIM, KPC, OXA-48 and IMP) and extended-spectrum beta
      lactamase (ESBL) gene families (SHV, TEM and CTX-M). The test performance of this
      microarray was evaluated with 95 Enterobacteriaceae isolates suspected of being
      carbapenemase producers, i.e. with meropenem MICs >=0.5 mg l(-1). The collection
      of isolates contained 70 carbapenemase-producing isolates, including 37 bla(KPC)
      , 20 bla(VIM)-, five bla(OXA-48)-, four bla(KPC)/bla(VIM)- and four bla(NDM)
      positive isolates; and 25 carbapenemase-gene-negative isolates. ESBLs were
      produced by 51 of the isolates. PCR and sequencing of beta-lactamase genes was
      used as reference test. For detection of carbapenemases, the sensitivity of the
      microarray was 97% (68/70), with 100% specificity. The two negative isolates
      tested positive when the microarray test was repeated; these isolates were an OXA
      48- and a KPC-producing isolate. For ESBL detection, the sensitivity was 100%
      (51/51) and the specificity was 98% (43/44), although 20% of the SHV-12 ESBLs
      were categorized as SHV-2-like ESBLs. In conclusion, the CDT102 microarray is a
      rapid and accurate tool for the detection of carbapenemase and ESBL genes,
      although the array seems less suitable for epidemiology of ESBL genes.

PMID- 22383445
TI  - Molecular epidemiology of the attachment glycoprotein (G) gene in respiratory
      syncytial virus in children with acute respiratory infection in Japan in
      2009/2010.
AB  - This study performed a detailed genetic analysis of the glycoprotein (G) gene of
      respiratory syncytial virus (RSV) detected in 50 Japanese children with acute
      respiratory infection (ARI) in the 2009/2010 season. A phylogenetic tree
      constructed by the neighbour-joining method showed that 34 and 16 of the RSV
      strains could be classified into subgroups A and B, respectively. Strains
      belonging to subgroups A and B were further subdivided into GA2 and BA,
      respectively. The nucleotide and deduced amino acid sequence identities were
      relatively high among these strains (>90%). The deduced amino acid sequences
      implied that a relatively high frequency of amino acid substitutions occurred in
      the C-terminal 3rd hypervariable region of the G protein in these strains. In
      addition, some positively selected sites were estimated. The results suggest that
      RSV with genotypes GA2 and BA was associated with ARI in Japanese children in
      2009/2010.

PMID- 22383446
TI  - Photovoltaic device on a single ZnO nanowire p-n homojunction.
AB  - A photovoltaic device was successfully grown solely based on the single ZnO p-n
      homojunction nanowire. The ZnO nanowire p-n diode consists of an as-grown n-type
      segment and an in situ arsenic-doped p-type segment. This p-n homojunction acts
      as a good photovoltaic cell, producing a photocurrent almost 45 times larger than
      the dark current under reverse-biased conditions. Our results demonstrate that
      the present ZnO p-n homojunction nanowire can be used as a self-powered
      ultraviolet photodetector as well as a photovoltaic cell, which can also be used
      as an ultralow electrical power source for nanoscale electronic, optoelectronic
      and medical devices.

PMID- 22383448
TI  - A very happy and successful 2012.

PMID- 22383447
TI  - Preparation of allyl and vinyl silanes by the palladium-catalyzed silylation of
      terminal olefins: a silyl-Heck reaction.

PMID- 22383449
TI  - A globalization-oriented perspective on health, inequality and socio-economic
      development.
AB  - OBJECTIVES: There has been an attention to inequality as a causal factor for
      deficient health in the medical journals over the last decades (Richard G.
      Wilkinson et al. and Schnell et al.); however, the reasons for inequality and the
      interactions of the underlying causes of inequality at the level of the world
      economy have not yet been properly explored in this kind of literature. The aim
      of this article is to provide a new, globalization-oriented, multi-disciplinary
      perspective on life expectancy, under-five mortality, inequality and socio
      economic development in the world system, compatible with the advances in
      international sociological research on the subject over the last three decades.
      DESIGN: Taking up the traditions of quantitative sociology to study the effects
      of multinational corporation (MNC) penetration as a key determining variable for
      development outcomes such as socio-economic inequality and infant mortality, this
      article analyzes from the perspective of quantitative political science and
      economics this particular role of MNC penetration as the key variable for the
      determination of health, inequality and socio-economic development in 183
      countries of the world system, using international social science standard data.
      MAIN OUTCOMES: As correctly predicted by quantitative sociology, but largely
      overlooked by the medical profession, the development style, implied by a high
      MNC penetration of their host countries, reflects the oligopolistic power, which
      transnational corporations wield over local economies. We took up an idea from
      Austro-American economist Joseph Alois Schumpeter (1883-1950), which states that
      the long-term effects of oligopolistic power are negative and lead toward
      economic and social stagnation. Our data show that although MNC penetration
      indeed led to certain short-term growth effects after 1990, today, social
      polarization and stagnation increase as a consequence of the development model,
      based on high MNC penetration. There is a negative trade-off between MNC
      penetration and health, both in terms of life expectancy and avoiding under-five
      mortality. But it can be shown for the 115 countries with complete data that
      Richard G. Wilkinson's hypothesis still plays an important role in explaining
      deficient health development in the world system, once we control for the effects
      of MNC penetration-driven globalization.

PMID- 22383451
TI  - Advances in intestinal microecology: the microbiome, prebiotics, and probiotics.

PMID- 22383452
TI  - Shape-dependent surface-enhanced Raman scattering in gold-Raman probe-silica
      sandwiched nanoparticles for biocompatible applications.
AB  - To meet the requirement of Raman probes (labels) for biocompatible applications,
      a synthetic approach has been developed to sandwich the Raman-probe (malachite
      green isothiocyanate, MGITC) molecules between the gold core and the silica shell
      in gold-SiO2 composite nanoparticles. The gold-MGITC-SiO2 sandwiched structure
      not only prevents the Raman probe from leaking out but also improves the
      solubility of the nanoparticles in organic solvents and in aqueous solutions even
      with high ionic strength. To amplify the Raman signal, three types of core, gold
      nanospheres, nanorods and nanostars, have been chosen as the substrates of the
      Raman probe. The effect of the core shape on the surface-enhanced Raman
      scattering (SERS) has been investigated. The colloidal nanostars showed the
      highest SERS enhancement factor while the nanospheres possessed the lowest SERS
      activity under excitation with 532 and 785 nm lasers. Three-dimensional finite
      difference time domain (FDTD) simulation showed significant differences in the
      local electromagnetic field distributions surrounding the nanospheres, nanorods,
      and nanostars, which were induced by the localized surface plasmon resonance
      (LSPR). The electromagnetic field was enhanced remarkably around the two ends of
      the nanorods and around the sharp tips of the nanostars. This local
      electromagnetic enhancement made the dominant contribution to the SERS
      enhancement. Both the experiments and the simulation revealed the order nanostars
      > nanorods > nanospheres in terms of the enhancement factor. Finally, the
      biological application of the nanostar-MGITC-SiO2 nanoparticles has been
      demonstrated in the monitoring of DNA hybridization. In short, the gold-MGITC
      SiO2 sandwiched nanoparticles can be used as a Raman probe that features high
      sensitivity, good water solubility and stability, low-background fluorescence,
      and the absence of photobleaching for future biological applications.

PMID- 22383453
TI  - A versatile rhodium(I) catalyst system for the addition of heteroarenes to both
      alkenes and alkynes by a C-H bond activation.

PMID- 22383454
TI  - Pacemaker clinics and anticoagulation for atrial fibrillation.

PMID- 22383455
TI  - Septal pacing: ready for prime time?

PMID- 22383456
TI  - The role of stress test for predicting genetic mutations and future cardiac
      events in asymptomatic relatives of catecholaminergic polymorphic ventricular
      tachycardia probands.
AB  - AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an
      inherited arrhythmic disorder with a highly malignant clinical course. Exercise
      stress test is the first-line approach to diagnose suspected individuals. We
      sought to elucidate the value of exercise-stress test for predicting mutations
      and future cardiac events in CPVT-family relatives. METHODS AND RESULTS: The
      present study included 67 asymptomatic relatives (24 +/- 15 years) of 17
      genetically positive CPVT probands, who underwent exercise-stress test without
      any medication and genetic testing. Exercise-stress test, which was considered
      positive with the induction of ventricular tachycardia or premature ventricular
      contractions consisting of bigeminy or couplets, was positive in 17 relatives
      (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and
      in 16 of the 50 relatives (32%) with negative exercise-stress test; the
      sensitivity and specificity for a positive genotype were 50 and 97%, respectively
      (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16
      relatives with positive and 2 of the 16 relatives with negative exercise-stress
      test during the follow-up period of 9.6 +/- 3.8 years, and four with positive and
      two with negative stress test were not on regular beta-blocker treatment at these
      events. In the 16 relatives with positive stress test, those on beta-blocker
      treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054).
      CONCLUSION: In asymptomatic relatives of CPVT probands, exercise-stress test can
      be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity
      for predicting mutations and future cardiac events in those with negative stress
      test, genetic analysis should be performed to improve patient management.

PMID- 22383457
TI  - More bone density testing is needed, not less.

PMID- 22383458
TI  - Topology evolution of graphene in chemical vapor deposition, a combined
      theoretical/experimental approach toward shape control of graphene domains.
AB  - Morphology control of thin film relies on understanding multiple ongoing
      processes during deposition and growth. To reveal the shape evolution of graphene
      domains on copper surfaces in chemical vapor deposition (CVD), a combinative
      study is performed on the CVD growth of graphene on copper surfaces. To identify
      the factors that influence the adsorption and diffusion of carbon atoms and
      further determine the domain shape, simulations based on kinetic Monte Carlo
      techniques are carried out. The results reveal the dependence of the graphene
      domain shapes on the crystalline orientation of the underlying copper substrate
      surfaces.

PMID- 22383459
TI  - Does passive smoking have an effect on nasal mucociliary clearance?
AB  - OBJECTIVE: The aim of this study is to review the literature about nasal
      mucociliary clearance (MCC) and passive smoking in otorhinolaryngology by clearly
      explaining their relationship in a cross-sectional study. STUDY DESIGN AND
      SETTING: This cross-sectional study was conducted at the Umraniye Education and
      Research Hospital in Turkey. Umraniye Education and Research Hospital Ethical
      Committee approved the study, and informed consents of the patients were
      obtained. METHODS: Our study consisted of patients who presented to the Ear-Nose
      Throat Department of Istanbul Umraniye Education and Research Hospital between
      February 2011 and July 2011. Three groups of subjects were evaluated: 15 passive
      smokers (group 1), 17 active smokers (group 2), and 15 healthy matched controls
      (group 3). All patients were asked to answer our questions regarding their
      smoking history, and nasal MCC time was assessed for all individuals of the 3
      groups. RESULTS: The mean MCC value was 23.59 +/- 12.41 in the smoking group,
      12.6 +/- 4.67 in the passive smoking group, and 6.4 +/- 1.55 in the healthy
      group. The comparison of MCC values between the smoking group and passive smoking
      group and between the smoking group and healthy group revealed statistically
      significant differences (P < .01). There was also a significant difference
      between the MCC values of the passive smoking group and the healthy group (P <
      .01). In addition, we compared MCC values according to exposure number of
      cigarettes. CONCLUSION: In this study, we conclude that passive smoking affects
      nasal MCC. Both active and passive smoking increases nasal MCC time when compared
      with healthy controls.

PMID- 22383461
TI  - TEX11 modulates germ cell proliferation by competing with estrogen receptor beta
      for the binding to HPIP.
AB  - Klinefelter syndrome (KS), characterized by the presence of more than one X
      chromosome in men, is a major genetic cause of male infertility. Germ cell
      degeneration in KS patients is thought to be the consequences of overexpression
      of some genes on the X-chromosome. However, the identity of these genes and the
      underlying mechanisms remain unclear. Testis-expressed 11 (TEX11) is an X
      chromosome-encoded germ-cell-specific protein that is expressed most abundantly
      in spermatogonia and early spermatocytes in the testes. In our search for TEX11
      interacting partners using the yeast two-hybrid system, we identified
      hematopoietic pre-B cell leukemia transcription factor-interacting protein
      (HPIP), which anchors estrogen receptors (ER) to the cytoskeleton and modulates
      their functions. We found that mouse spermatogonial stem cells expressed Tex11,
      Hpip, and Esr2 but not Esr1. In cultured cells, TEX11 competed with ERbeta for
      binding to HPIP. Upon treatment with 17beta-estradiol or an ERbeta agonist
      diarylpropionitrile, TEX11 promoted the nuclear translocation of ERbeta and
      enhanced its transcriptional activities. On the other hand, TEX11 suppressed the
      nongenomic activities of ERbeta in the cytoplasm, as indicated by reduced
      phosphorylation of AKT and ERK signaling molecules. Overexpression of TEX11 in
      mouse germ-cell-derived GC-1 and GC-2 cells suppressed the cell proliferation and
      the expression of cFos, Ccnd1, and Ccnb1 that were stimulated by 17beta-estradiol
      or diarylpropionitrile and elevated the expression level of the proapoptotic Bax
      gene. The negative effect of TEX11 on cell proliferation suggests that increased
      expression of TEX11 in the germ cells may partially contribute to the
      spermatogenic defect observed in KS patients.

PMID- 22383462
TI  - Endoplasmic reticulum (ER) stress in cumulus-oocyte complexes impairs pentraxin-3
      secretion, mitochondrial membrane potential (DeltaPsi m), and embryo development.
AB  - Fatty acids such as palmitic acid at high levels are known to induce endoplasmic
      reticulum (ER) stress and lipotoxicity in numerous cell types and thereby
      contribute to cellular dysfunctions in obesity. To understand the impact of high
      fatty acids on oocytes, ER stress and lipotoxicity were induced in mouse cumulus
      oocyte complexes during in vitro maturation using the ER Ca(2+) channel blocker
      thapsigargin or high physiological levels of palmitic acid; both of which
      significantly induced ER stress marker genes (Atf4, Atf6, Xbp1s, and Hspa5) and
      inositol-requiring protein-1alpha phosphorylation, demonstrating an ER stress
      response that was reversible with the ER stress inhibitor salubrinal. Assessment
      of pentraxin-3, an extracellular matrix protein essential for fertilization, by
      immunocytochemistry and Western blotting showed dramatically impaired secretion
      concurrent with ER stress. Mitochondrial activity in oocytes was assessed by
      5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide
      staining of inner mitochondrial membrane potential, and oocytes matured in
      thapsigargin or high-dose palmitic acid had significantly reduced mitochondrial
      activity, reduced in vitro fertilization rates, and were slower to develop to
      blastocysts. The deficiencies in protein secretion, mitochondrial activity, and
      oocyte developmental competence were each normalized by salubrinal, demonstrating
      that ER stress is a key mechanism mediating fatty acid-induced defects in oocyte
      developmental potential.

PMID- 22383463
TI  - mRNA-selective translation induced by FSH in primary Sertoli cells.
AB  - FSH is a key hormonal regulator of Sertoli cell secretory activity, required to
      optimize sperm production. To fulfil its biological function, FSH binds a G
      protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network
      ultimately leads to the transcription or down-regulation of numerous genes. In
      addition, recent evidence has suggested that FSH might also regulate protein
      translation. However, this point has never been demonstrated conclusively yet.
      Here we have addressed this issue in primary rat Sertoli cells endogenously
      expressing physiological levels of FSH-R. We observed that, within 90 min of
      stimulation, FSH not only enhanced overall protein synthesis in a mammalian
      target of rapamycin-dependent manner but also increased the recruitment of mRNA
      to polysomes. m(7)GTP pull-down experiments revealed the functional recruitment
      of mammalian target of rapamycin and p70 S6 kinase to the 5'cap, further
      supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the
      eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic
      initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E
      binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared
      to play a minor role in translational regulations induced by FSH, in contrast to
      what is generally observed in response to anabolic factors. This particular
      regulation of the translational machinery by FSH stimulation might support mRNA
      selective translation, as shown here by quantitative RT-PCR amplification of the
      c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA,
      in polysomal fractions. These findings add a new level of complexity to FSH
      biological roles in its natural target cells, which has been underappreciated so
      far.

PMID- 22383473
TI  - The pknH gene restrictively expressed in heterocysts is required for diazotrophic
      growth in the cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium in which certain
      vegetative cells differentiate into heterocysts, which are specialized cells for
      nitrogen fixation. Heterocysts are unable to carry out photosynthesis and are
      supplied with carbohydrate required for nitrogen fixation from neighbouring
      vegetative cells. Thus, filament integrity is very important for diazotrophic
      growth of the heterocystous cyanobacteria. The pknH gene (alr1336), encoding a
      putative Ser/Thr protein kinase, was upregulated in heterocysts after nitrogen
      deprivation. Its expression was developmentally regulated by the hetR gene.
      Expression levels of genes involved in heterocyst maturation, such as hepA, hglE
      and nifH, in the pknH disruptant were similar to those of the wild-type strain.
      The disruptant was able to form heterocysts with nitrogenase activity, but most
      heterocysts were detached from filaments. Hence, the pknH disruptant showed a
      growth defect in the medium without combined nitrogen. It is concluded that the
      pknH gene is not involved in the development of heterocyst function but is
      involved in maintaining connections between heterocysts and vegetative cells.

PMID- 22383464
TI  - The rs3743205 SNP is important for the regulation of the dyslexia candidate gene
      DYX1C1 by estrogen receptor beta and DNA methylation.
AB  - Estrogen is involved in numerous physiological processes such as growth,
      differentiation, and function of the male and female reproductive tissues. In the
      developing brain, estrogen signaling has been linked to cognitive functions, such
      as learning and memory; however, the molecular mechanisms underlying this
      phenomenon are poorly understood. We have previously shown a link between
      developmental dyslexia and estrogen signaling, when we studied the functional
      interactions between the dyslexia candidate protein DYX1C1 and the estrogen
      receptors alpha (ERalpha) and beta (ERbeta). Here, we investigate the 17beta
      estradiol (E2)-dependent regulation of dyslexia susceptibility 1 candidate 1
      (DYX1C1) expression. We demonstrate that ERbeta, not ERalpha, binds to a
      transcriptionally active cis-regulatory region upstream of DYX1C1 transcriptional
      start site and that DYX1C1 expression is enhanced by E2 in a neuroblastoma cell
      line. This regulation is dependent on transcription factor II-I and liganded
      ERbeta recruitment to this region. In addition, we describe that a single
      nucleotide polymorphism previously shown to be associated with dyslexia and
      located in the cis-regulatory region of DYX1C1 may alter the epigenetic and
      endocrine regulation of this gene. Our data provide important molecular insights
      into the relationship between developmental dyslexia susceptibility and estrogen
      signaling.

PMID- 22383475
TI  - Does country-context matter? A cross-national analysis of gender and leisure time
      physical inactivity in Europe.
AB  - BACKGROUND: It is well known that European women are less physically active in
      their leisure time than European men. Attempts to explain this gender difference
      often do not succeed in raising the problem above the individual level. However,
      the size of the disadvantage for women varies considerably across countries,
      proving that leisure time physical (in)activity takes place in a broader societal
      context and must also be approached as such. In this sense, some authors have
      explained women's lack of leisure time physical activity in terms of gendered
      power relations in society. Therefore, the present article postulates that over
      and above the individual effect of gender, there is an additional impact of a
      society's gender-based (in)equality distribution. METHODS: By means of the 2005
      Eurobarometer survey (comprising 25,745 adults from 27 European countries),
      gender differences in leisure time physical inactivity (LTPI) were analysed by
      means of multilevel logistic regression analysis. National gender-based
      (in)equality was measured by the Gender Empowerment Measure and the Gender Gap
      Index. RESULTS: Controlled for compositional effects, gender differences in LTPI
      varied as a function of gender-related characteristics at the macro-level. In
      particular, in countries characterized by high levels of gender-based equality,
      LTPI differences between men and women even disappeared. CONCLUSION: The findings
      underscore the need to adopt a society-level approach and to incorporate socio
      contextual factors in the study of gender disparities in LTPI.

PMID- 22383474
TI  - Vru (Sub0144) controls expression of proven and putative virulence determinants
      and alters the ability of Streptococcus uberis to cause disease in dairy cattle.
AB  - The regulation and control of gene expression in response to differing
      environmental stimuli is crucial for successful pathogen adaptation and
      persistence. The regulatory gene vru of Streptococcus uberis encodes a stand
      alone response regulator with similarity to the Mga of group A Streptococcus. Mga
      controls expression of a number of important virulence determinants. Experimental
      intramammary challenge of dairy cattle with a mutant of S. uberis carrying an
      inactivating lesion in vru showed reduced ability to colonize the mammary gland
      and an inability to induce clinical signs of mastitis compared with the wild-type
      strain. Analysis of transcriptional differences of gene expression in the mutant,
      determined by microarray analysis, identified a number of coding sequences with
      altered expression in the absence of Vru. These consisted of known and putative
      virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785)
      and hasA (Sub1696).

PMID- 22383476
TI  - Risk behaviour in Swedish adolescents: is shared physical custody after divorce a
      risk or a protective factor?
AB  - BACKGROUND: The increase in shared physical custody in Sweden has been dramatic;
      20 years ago only a small percentage of adolescents lived in shared physical
      custody, but currently ~30% of the adolescents whose parents have separated or
      divorced divide their residence between parents. We hypothesized that living in
      shared physical custody or in a single-parent family is associated with a higher
      prevalence of adolescent risk behaviour than living in a two-parent family.
      METHODS: Data on 15-year-old adolescents from the 2005/2006 to 2009/2010 Swedish
      Health Behaviour in School-aged Children (HBSC) survey were analysed using
      logistic regression. RESULTS: Adolescents living in shared physical custody had
      slightly higher rates of risk behaviour compared with adolescents from two-parent
      families, but significantly lower rates than their counterparts from single
      parent families. Their odds of being a smoker or having been drunk were 60 and
      50% higher, respectively, than those of their counterparts in two-parent
      families. CONCLUSION: Shared physical custody after marriage break-up seems to
      constitute a health protective factor for adolescents' health and problem
      behaviour. In order to deepen our understanding of the positive and negative
      aspects of shared physical custody, our study should be followed by qualitative
      analyses and longitudinal studies of adolescents' experiences.

PMID- 22383477
TI  - Attitudes and perceptions of influenza vaccination among Hong Kong doctors and
      medical students before the 2009 pandemic.
AB  - BACKGROUND: Vaccination is an important preventive measure for preparing against
      the influenza pandemics. This study investigated the attitudes and perceptions of
      influenza vaccination among doctors and medical students in Hong Kong. METHODS: A
      cross-sectional survey was conducted among 204 doctors and 242 medical students
      in a teaching hospital in 2009. Participants' demographic and job
      characteristics, and influenza experience and vaccination in the previous year
      were assessed in the questionnaire. Logistic regression models were used to
      examine the associations between uptake of influenza vaccination and the
      perceived benefits. RESULTS: Medical students were more likely to have receive an
      influenza vaccination in the previous year (66.9 vs. 39.7%) and acknowledged the
      related benefits than doctors. Moreover, uptake of influenza vaccine was
      associated with perceived benefits of vaccination in both doctors and medical
      students. CONCLUSIONS: The perceived benefits of influenza vaccination are an
      important factor in vaccine uptake for both doctors and medical students in Hong
      Kong, and should be reinforced in the professional training.

PMID- 22383478
TI  - Sleep disturbances and fatigue: independent predictors of sickness absence? A
      prospective study among 6538 employees.
AB  - BACKGROUND: Although sleep disturbances and fatigue are common conditions,
      frequently shown to be associated with sickness absence, only a few studies have
      prospectively investigated their independent effects on sickness absence, while
      adjusting for depressive symptoms. This study aims (i) to examine whether sleep
      disturbances and fatigue are independently related to the onset of register-based
      sickness absence of >= 3 weeks during a 1-year follow-up in a representative
      sample of the Danish workforce and (ii) to determine if possible associations are
      gender-specific. METHODS: Data were used from the Danish Work Environment Cohort
      Study and linked with sickness absence data from the Danish National Register of
      Social Transfer Payments. A total of 6538 employees, 3178 men and 3360 women,
      were included in the analyses. RESULTS: Sleep disturbances predicted risk of
      sickness absence after adjustment for covariates, but lost statistical
      significance after further adjustment for depressive symptoms. Fatigue among men
      predicted risk of sickness absence [Hazard ratio (HR) = 1.25, 95% confidence
      intervals (CI) 1.00-1.56] after adjustment for covariates, depressive symptoms
      and sleep disturbances. CONCLUSION: Sleep disturbances in both genders and
      fatigue in women did not predict sickness absence after depressive symptoms were
      taken into account. In men, fatigue was significantly related to future sickness
      absence, also when adjusted for depressive symptoms and sleep disturbances.
      Further prospective studies are needed to explore the pathways from fatigue to
      sickness absence in more detail. The study suggests that early detection and
      treatment of fatigue in men should be high on the stakeholder's agenda.

PMID- 22383479
TI  - Use of the emergency Incident Command System for school-located mass influenza
      vaccination clinics.
AB  - In Palm Beach County, Florida, the fall 2005 influenza vaccination season was
      interrupted by Hurricane Wilma, a particularly destructive storm that resulted in
      flooding, power outages, extensive property damage, and suspension of many
      routine community services. In its aftermath, all public health resources were
      immediately turned to the response and recovery process. School-located mass
      influenza vaccination (SLV) clinics were scheduled to begin in 1 week, but were
      necessarily postponed for a month. The juxtaposition of these 2 major public
      health events afforded the school district, health department, and other
      community services an opportunity to see their similarities and adopt the
      Incident Command System structure to manage the SLV clinics across West Palm
      Beach County, Florida, a geographically large county. Other lessons were learned
      during the hurricane concerning organizations and people, processes, and
      communications, and were applicable to school-located mass influenza vaccination
      programs, and vice versa. Those lessons are related here.

PMID- 22383480
TI  - Epilogue: school-located influenza vaccination during the 2009-2010 pandemic and
      beyond.

PMID- 22383481
TI  - Evolution of the pediatric influenza vaccination program in the United States.

PMID- 22383482
TI  - Expanding the recommendations for annual influenza vaccination to school-age
      children in the United States.
AB  - BACKGROUND: Despite long-standing recommendations to vaccinate children who have
      underlying chronic medical conditions or who are contacts of high-risk persons,
      vaccination coverage among school-age children remains low. Community studies
      have indicated that school-age children have the highest incidence of influenza
      and are an important source of amplifying and sustaining community transmission
      that affects all age groups. METHODS: A consultation to discuss the advantages
      and disadvantages of a universal recommendation for annual influenza vaccination
      of all children age >=6 months was held in Atlanta, Georgia, in September 2007.
      Consultants provided summaries of current data on vaccine effectiveness, safety,
      supply, successful program implementation, and economics studies and discussed
      challenges associated with continuing a risk- and contact-based vaccination
      strategy compared with a universal vaccination recommendation. RESULTS:
      Consultants noted that school-age children had a substantial illness burden
      caused by influenza, that vaccine was safe and effective for children aged 6
      months through 18 years, and that evidence suggested that vaccinating school-age
      children would provide benefits to both the vaccinated children and their
      unvaccinated household and community contacts. However, implementation of an
      annual recommendation for all school-age children would pose major challenges to
      parents, medical providers and health care systems. Alternative vaccination
      venues were needed, and of these school-located vaccination programs might offer
      the most promise as an alternative vaccination site for school-age children.
      CONCLUSIONS: Expansion of recommendations to include all school-age children will
      require additional development of an infrastructure to support implementation and
      methods to adequately evaluate impact.

PMID- 22383483
TI  - A theoretic framework to consider the effect of immunizing schoolchildren against
      influenza: implications for research.
AB  - The illness attack rate and annual morbidity caused by infection with influenza
      is high in schoolchildren. Because schoolchildren are 1 of the most important
      sources of community-wide transmission of influenza, vaccinating them could have
      a major effect on reducing morbidity and mortality in older adults. Stochastic
      modeling shows that a vaccination rate as low as 20% in schoolchildren reduces
      overall mortality in adults aged >=64 years more effectively than a vaccination
      rate of 90% for older adults. Additional modeling shows that vaccinating
      schoolchildren against influenza is optimal for reducing morbidity and mortality
      caused by influenza in the overall population. Although supported by simulated
      models, the benefits of mass vaccination need to be confirmed in a real-world
      setting. The best way to demonstrate the effectiveness of mass vaccination of
      schoolchildren is to implement the process in several localities in several
      states by using properly designed studies that incorporate accurate viral
      surveillance with at least 10 pairs of intervention and comparison populations.

PMID- 22383484
TI  - Early experience conducting school-located vaccination programs for seasonal
      influenza.
AB  - OBJECTIVES: We determined program effectiveness, feasibility, and acceptance of
      school-located vaccination (SLV) clinics for seasonal influenza that took place
      before the 2008 universal influenza vaccination recommendations. METHODS: We
      surveyed program directors of 23 programs in the United States who conducted SLV
      clinics during the 2005 to 2006 and 2006 to 2007 influenza seasons. RESULTS: Of
      391,423 children enrolled in schools with SLV clinics, 61,463 (15.7%) were
      vaccinated at 499 sites (schools) in 23 programs. Of these, 22 were small- and
      medium-sized programs that vaccinated 32,875 (24.1%) of the 136,151 children
      enrolled there, averaging 31.9% of students per site. One populous county
      vaccinated an additional 28,588 (11.2%) of its 255,272 enrolled children,
      averaging 13.9% per school. Children in grades K to 6 had consistently higher
      mean vaccination rates (21.5%) compared with middle school children (10.3%) or
      high school youth (5.8%). Program acceptability was high, and no program had to
      forego any key public health activities; 5 hired temporary help or paid overtime.
      The outlook for continuing such clinics was good in 7 programs, but depended on
      help with vaccine purchasing (9), funding (8), or additional personnel (4), with
      multiple responses allowed. CONCLUSIONS: These vaccination coverage rates provide
      a baseline for future performance of school-located mass vaccination clinics.
      Although the existence and conduct of these programs in our study was considered
      acceptable by leaders of public health departments and anecdotally by parents and
      school administrators, sustainability may require additional means to pay for
      vaccines or personnel beyond the usual available health department resources.

PMID- 22383485
TI  - Promising practices for school-located vaccination clinics--part I: preparation.
AB  - A school-located mass vaccination clinic approach can enable rapid vaccination of
      a large number of students while minimizing disruption of their school activities
      and potentially reducing missed work hours by parents. During 3 consecutive
      influenza seasons beginning in 2005, the Knox County Health Department conducted
      school-located mass vaccination clinics using live attenuated influenza vaccine.
      Clinics were held each year throughout the county over 4 weeks in more than 100
      public and private schools for more than 65, 000 students in Grades K to 12.
      Overall, the proportion of all students vaccinated at school each year exceeded
      40%. Our experience indicated that careful and thorough planning was essential to
      program success. Critical planning elements included (1) initial planning with
      extensive lead time to find the proper lead agency and project leader and to
      develop sound comprehensive vaccine clinic planning; (2) developing partnerships,
      especially with schools; (3) communicating successfully with parents, children,
      school administrators and teachers, medical providers, and the community at
      large; and (4) educating these groups successfully, using good timing, through
      local media, school events, direct mailings (including parents receiving
      information and consent packets), and partners. We review here the details of
      these key planning elements.

PMID- 22383486
TI  - Promising practices for school-located vaccination clinics-- part II: clinic
      operations and program sustainability.
AB  - A school-located mass vaccination program can enable rapid vaccination of a large
      number of students while minimizing disruption of their school activities. During
      3 consecutive influenza seasons beginning in 2005, the Knox County Health
      Department conducted school-located mass vaccination clinics using live
      attenuated influenza vaccine. Overall, the proportion of elementary
      schoolchildren vaccinated with live attenuated influenza vaccine exceeded 40%
      each year. We describe key lessons learned in clinic operations, including
      obtaining informed consent, defining the organizational structure and roles,
      preparing the school, staffing, training, supplies, vaccine management, team
      communication, and data management. We conclude by discussing program costs and
      sustainability.

PMID- 22383487
TI  - Successful use of volunteers to conduct school-located mass influenza vaccination
      clinics.
AB  - OBJECTIVE: To determine the feasibility of using volunteers to assist in school
      located mass vaccination clinics for influenza. METHODS: A set of elementary
      school-based mass vaccination clinics was implemented in Carroll County, Maryland
      by the local health department in the 2005-2006 school year. In addition to using
      health department personnel, fiscal restraints necessitated using medical
      volunteers and lay volunteers to assist health professionals. The medical
      volunteers included physicians, nurses, and pharmacists, and were responsible for
      administering intranasal vaccine (live, attenuated influenza vaccine [LAIV]). We
      assessed the performance, as measured by the number of vaccinations administered,
      and effort expended by these volunteers. RESULTS: A total of 5319 (44%) of the
      12,090 elementary school children in the county received LAIV. Of the estimated
      3547 (66%) children eligible and consenting to receive a second dose, 3124 (88%)
      received it. In total, 8806 doses of LAIV were administered. Health department
      nurses worked 42 person-days and were assisted by medical and allied health
      professionals volunteering 87 person-days without compensation, totaling 581
      person-hours spent in this effort. CONCLUSIONS: A mass school-located influenza
      vaccination program using medical and lay volunteers guided by health department
      nurses is feasible. Several issues were identified to improve future clinics and
      help make the program sustainable.

PMID- 22383488
TI  - Pediatrician attitudes concerning school-located vaccination clinics for seasonal
      influenza.
AB  - OBJECTIVE: Vaccinating all children aged 6 months to 18 years every year has
      potentially large ramifications for office-based primary care pediatricians. We
      determined the degree to which pediatricians support routine annual influenza
      vaccination outside the medical home, especially in school-located mass influenza
      vaccination clinics. METHODS: Internet-based survey sent in May and June 2009 to
      all 623 currently practicing primary care general pediatricians who were members
      of the Maryland Chapter of the American Academy of Pediatrics. RESULTS: Of those
      surveyed, 193 (31%) responded. Approximately 67% reported they vaccinated more
      than half the children in their practice with at least one dose in the 2008-2009
      influenza season, and about half anticipated that, in their office, they would
      not attain >=75% coverage of all patients older than 5 months of age.
      Approximately 27% of respondents predicted they would likely have difficulty
      obtaining sufficient vaccine to cover commercially insured patients, and 32% were
      likely to have difficulty getting sufficient vaccine to cover Medicaid,
      underinsured, and uninsured patients because of ordering or distribution
      problems. Approximately 78% of respondents cited borderline or poor reimbursement
      for influenza vaccinations, and 53% had unused vaccine at the end of the 2008
      2009 influenza season. Ninety-six percent of respondents supported school-located
      influenza vaccination programs in their community for their patients.
      CONCLUSIONS: These results indicate awareness by primary care pediatricians in
      Maryland of the potential difficulties involved in implementing universal
      influenza vaccinations in their practice and their support of school-located
      vaccination programs managed by the local health department in their community.

PMID- 22383489
TI  - Identification of copy number variants in horses.
AB  - Copy number variants (CNVs) represent a substantial source of genetic variation
      in mammals. However, the occurrence of CNVs in horses and their subsequent impact
      on phenotypic variation is unknown. We performed a study to identify CNVs in 16
      horses representing 15 distinct breeds (Equus caballus) and an individual gray
      donkey (Equus asinus) using a whole-exome tiling array and the array comparative
      genomic hybridization methodology. We identified 2368 CNVs ranging in size from
      197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions
      (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per
      animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and
      99.4 kb, respectively. Approximately 6% of the genes investigated were affected
      by a CNV. Biological process enrichment analysis indicated CNVs primarily
      affected genes involved in sensory perception, signal transduction, and
      metabolism. CNVs also were identified in genes regulating blood group antigens,
      coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and
      height in other species. Collectively, these data are the first report of copy
      number variation in horses and suggest that CNVs are common in the horse genome
      and may modulate biological processes underlying different traits observed among
      horses and horse breeds.

PMID- 22383490
TI  - P2X7 receptor-mediated purinergic signaling promotes liver injury in
      acetaminophen hepatotoxicity in mice.
AB  - Inflammation contributes to liver injury in acetaminophen (APAP) hepatotoxicity
      in mice and is triggered by stimulation of immune cells. The purinergic receptor
      P2X7 is upstream of the nod-like receptor family, pryin domain containing-3
      (NLRP3) inflammasome in immune cells and is activated by ATP and NAD that serve
      as damage-associated molecular patterns. APAP hepatotoxicity was assessed in mice
      genetically deficient in P2X7, the key inflammatory receptor for nucleotides
      (P2X7-/-), and in wild-type mice. P2X7-/- mice had significantly decreased APAP
      induced liver necrosis. In addition, APAP-poisoned mice were treated with the
      specific P2X7 antagonist A438079 or etheno-NAD, a competitive antagonist of NAD.
      Pre- or posttreatment with A438079 significantly decreased APAP-induced necrosis
      and hemorrhage in APAP liver injury in wild-type but not P2X7-/- mice.
      Pretreatment with etheno-NAD also significantly decreased APAP-induced necrosis
      and hemorrhage in APAP liver injury. In addition, APAP toxicity in mice lacking
      the plasma membrane ecto-NTPDase CD39 (CD39-/-) that metabolizes ATP was examined
      in parallel with the use of soluble apyrase to deplete extracellular ATP in wild
      type mice. CD39-/- mice had increased APAP-induced hemorrhage and mortality,
      whereas apyrase also decreased APAP-induced mortality. Kupffer cells were treated
      with extracellular ATP to assess P2X7-dependent inflammasome activation. P2X7 was
      required for ATP-stimulated IL-1beta release. In conclusion, P2X7 and exposure to
      the ligands ATP and NAD are required for manifestations of APAP-induced
      hepatotoxicity.

PMID- 22383491
TI  - Coordination of motilin and ghrelin regulates the migrating motor complex of
      gastrointestinal motility in Suncus murinus.
AB  - Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting
      state to stimulate the GI motility of the migrating motor complex (MMC). We
      focused on coordination of the ghrelin/motilin family in gastric contraction in
      vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and
      motilin-producing mammal. To measure the contractile activity of the stomach in
      vivo, we recorded GI contractions either in the free-moving conscious or
      anesthetized S. murinus and examined the effects of administration of motilin
      and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we
      also studied the coordinative effect of these hormones on the isolated stomach
      using an organ bath. In the fasting state, phase I, II, and III contractions were
      clearly recorded in the gastric body (as observed in humans and dogs).
      Intravenous infusion of ghrelin stimulated gastric contraction in the latter half
      of phase I and in the phase II in a dose-dependent manner. Continuous intravenous
      infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed
      spontaneous phase II contractions and prolonged the time of occurrence of the
      peak of phase III contractions. However, intravenous infusion of motilin
      antagonist (MA-2029) did not inhibit phase II contractions but delayed the
      occurrence of phase III contractions of the MMC. In the in vitro study, even
      though a high dose of ghrelin did not stimulate contraction of stomach
      preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a
      low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent
      manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric
      contractions by 10 times. The interrelation of these peptides was also
      demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is
      important for the phase II contraction and that coordination of motilin and
      ghrelin are necessary to initiate phase III contraction of the MMC.

PMID- 22383493
TI  - When GLP-1 hits the liver: a novel approach for insulin resistance and NASH.

PMID- 22383492
TI  - Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines.
AB  - Activating mutations in the KRAS oncogene are common in colorectal cancer.
      However, the complete spectrum of KRAS targets that mediate its tumorigenic
      effect has not yet been fully delineated. We identified bone morphogenetic
      protein 4 (Bmp4), a transforming growth factor-beta family member that regulates
      development and tissue homeostasis, as a new target of KRAS. In SW480, Hela, and
      293 cells, oncogenic KRAS(V12) downregulated BMP4 RNA levels, a BMP4 promoter
      luciferase construct, and Bmp4 protein levels. The MEK inhibitor PD98059 but not
      the phosphatidylinositol 3-kinase inhibitor LY294002 blocked this downregulation
      of BMP4. To identify the region of the BMP4 promoter that mediated this
      regulation by KRAS, serial 5'-deletions of the promoter were generated. An
      inhibitory region was identified between -3,285 and -3,258 bp in the Bmp4
      promoter. In summary, oncogenic KRAS can downregulate Bmp4 through a
      transcriptional pathway that depends on ERK. These findings point to a unique
      link between two pathways that are frequently altered in colon cancer.

PMID- 22383494
TI  - p38 MAPK regulates Bax activity and apoptosis in enterocytes at baseline and
      after intestinal resection.
AB  - Increased apoptosis in crypt enterocytes is a key feature of intestinal
      adaptation following massive small bowel resection (SBR). Expression of the
      proapoptotic factor Bax has been shown to be required for resection-induced
      apoptosis. It has also been demonstrated that p38-alpha MAPK (p38) is necessary
      for Bax activation and apoptosis in vitro. The present studies were designed to
      test the hypothesis that p38 is a key regulator of Bax activation during
      adaptation after SBR in vivo. Enterocyte expression of p38 was deleted by
      tamoxifen administration to activate villin-Cre in adult mice with a floxed
      Mapk14 (p38-alpha) gene. Proximal 50% SBR or sham operations were performed on
      wild-type (WT) and p38 intestinal knockout (p38-IKO) mice under isoflurane
      anesthesia. Mice were killed 3 or 7 days after operation, and adaptation was
      analyzed by measuring intestinal morphology, proliferation, and apoptosis. Bax
      activity was quantified by immunoprecipitation, followed by Western blotting.
      After SBR, p38-IKO mice had deeper crypts, longer villi, and accelerated
      proliferation compared with WT controls. Rates of crypt apoptosis were
      significantly lower in p38-IKO mice, both at baseline and after SBR. Levels of
      activated Bax were twofold higher in WT mice after SBR relative to sham. In
      contrast, activated Bax levels were reduced by 67% in mice after p38 MAPK
      deletion. Deleted p38 expression within the intestinal epithelium leads to
      enhanced adaptation and reduced levels of enterocyte apoptosis after massive
      intestinal resection. p38-regulated Bax activation appears to be an important
      mechanism underlying resection-induced apoptosis.

PMID- 22383495
TI  - DMT1 (IRE) expression in intestinal and erythroid cells is regulated by
      peripheral benzodiazepine receptor-associated protein 7.
AB  - The divalent metal transporter 1 (DMT1) is essential for cellular uptake of iron,
      mediating iron absorption across the duodenal brush border membrane. We have
      previously shown that with iron feeding DMT1 in the brush border membrane
      undergoes endocytosis into the subapical compartment of enterocytes. To
      understand the mechanisms of iron-induced endocytosis of DMT1, we used the yeast
      two-hybrid system to find proteins that interact with DMT1 and isolated from a
      rat duodenal cDNA library a protein that interacts specifically with the IRE
      containing isoform of DMT1 {DMT1 [iron-responsive element (IRE)]}. The protein
      (Genbank AY336075) is 97.5% identical with peripheral benzodiazepine receptor
      associated protein 7 (PAP7), a protein that interacts with the peripheral
      benzodiazepine receptor. PAP7 is ubiquitously expressed in the rat and in
      multiple cell lines with consensus sequences including a nuclear localization
      signal and a Golgi dynamic domain. PAP7, expressed on the brush border of rat
      duodenum, copurified with DMT1 in brush border membrane vesicles, and following
      iron feeding, was internalized in parallel with the internalization of DMT1. To
      determine if PAP7 plays a role in cellular iron metabolism, we downregulated PAP7
      expression in K562 cells with small interfering RNA. Following the decrease in
      PAP7 protein, DMT1 (IRE) protein but not mRNA was significantly downregulated but
      without effect on DMT1 (non-IRE), transferin (Tf)R1, or ferritin expression.
      Lowered levels of PAP7 resulted also in decreased cell proliferation and G(1)
      cell cycle arrest. These data are consistent with PAP7 interacting with DMT1
      (IRE) and regulating DMT1 (IRE) expression in K562 cells by modulating expression
      of DMT1 (IRE) protein.

PMID- 22383496
TI  - Commentaries on viewpoint: does SIRT1 determine exercise-induced skeletal muscle
      mitochondrial biogenesis: differences between in vitro and in vivo experiments?

PMID- 22383497
TI  - Last word on viewpoint: does SIRT1 determine exercise-induced skeletal muscle
      mitochondrial biogenesis: differences between in vitro and in vivo experiments?

PMID- 22383498
TI  - "Divide and conquer": assessing energy expenditure following physical activity
      type classification.

PMID- 22383502
TI  - Aerobic exercise reduces neuronal responses in food reward brain regions.
AB  - Acute exercise suppresses ad libitum energy intake, but little is known about the
      effects of exercise on food reward brain regions. After an overnight fast, 30 (17
      men, 13 women), healthy, habitually active (age = 22.2 +/- 0.7 yr, body mass
      index = 23.6 +/- 0.4 kg/m(2), Vo(2peak) = 44.2 +/- 1.5 ml.kg(-1).min(-1))
      individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest
      (no-exercise) in a counterbalanced, crossover fashion. After each condition,
      blood oxygen level-dependent responses to high-energy food, low-energy food, and
      control visual cues, were measured by functional magnetic resonance imaging.
      Exercise, compared with no-exercise, significantly (P < 0.005) reduced the
      neuronal response to food (high and low food) cues vs. control cues in the insula
      (-0.37 +/- 0.13 vs. +0.07 +/- 0.18%), putamen (-0.39 +/- 0.10 vs. -0.10 +/-
      0.09%), and rolandic operculum (-0.37 +/- 0.17 vs. 0.17 +/- 0.12%). Exercise
      alone significantly (P < 0.005) reduced the neuronal response to high food vs.
      control and low food vs. control cues in the inferior orbitofrontal cortex (-0.94
      +/- 0.33%), insula (-0.37 +/- 0.13%), and putamen (-0.41 +/- 0.10%). No-exercise
      alone significantly (P < 0.005) reduced the neuronal response to high vs. control
      and low vs. control cues in the middle (-0.47 +/- 0.15%) and inferior occipital
      gyrus (-1.00 +/- 0.23%). Exercise reduced neuronal responses in brain regions
      consistent with reduced pleasure of food, reduced incentive motivation to eat,
      and reduced anticipation and consumption of food. Reduced neuronal response in
      these food reward brain regions after exercise is in line with the paradigm that
      acute exercise suppresses subsequent energy intake.

PMID- 22383501
TI  - IL-18 induces emphysema and airway and vascular remodeling via IFN-gamma, IL-17A,
      and IL-13.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by
      chronic inflammation, alveolar destruction, and airway and vascular remodeling.
      However, the mechanisms that lead to these diverse alterations have not been
      defined. OBJECTIVES: We hypothesized that IL-18 plays a central role in the
      pathogenesis of these lesions. METHODS: We generated and characterized lung
      specific, inducible IL-18 transgenic mice. MEASUREMENTS AND MAIN RESULTS: Here we
      demonstrate that the expression of IL-18 in the mature murine lung induces
      inflammation that is associated with the accumulation of CD4(+), CD8(+), CD19(+),
      and NK1.1(+) cells; emphysema; mucus metaplasia; airway fibrosis; vascular
      remodeling; and right ventricle cardiac hypertrophy. We also demonstrate that IL
      18 induces type 1, type 2, and type 17 cytokines with IFN-gamma-inhibiting
      macrophage, lymphocyte, and eosinophil accumulation while stimulating alveolar
      destruction and genes associated with cell cytotoxicity and IL-13 and IL-17A
      inducing mucus metaplasia, airway fibrosis, and vascular remodeling. We also
      highlight interactions between these responses with IL-18 inducing IL-13 via an
      IL-17A-dependent mechanism and the type 1 and type17/type 2 responses
      counterregulating each another. CONCLUSIONS: These studies define the spectrum of
      inflammatory, parenchymal, airway, and vascular alterations that are induced by
      pulmonary IL-18; highlight the similarities between these responses and the
      lesions in COPD; and define the selective roles that type 1, type 2, and type 17
      responses play in the generation of IL-18-induced pathologies.

PMID- 22383500
TI  - 17beta-Estradiol attenuates hypoxic pulmonary hypertension via estrogen receptor
      mediated effects.
AB  - RATIONALE: 17beta-Estradiol (E2) attenuates hypoxic pulmonary vasoconstriction
      and hypoxic pulmonary hypertension (HPH) through an unknown mechanism that may
      involve estrogen receptors (ER) or E2 conversion to catecholestradiols and
      methoxyestradiols with previously unrecognized effects on cardiopulmonary
      vascular remodeling. OBJECTIVES: To determine the mechanism by which E2 exerts
      protective effects in HPH. METHODS: Male rats were exposed to hypobaric hypoxia
      while treated with E2 (75 MUg/kg/d) or vehicle. Subgroups were cotreated with
      pharmacologic ER-antagonist or with inhibitors of E2-metabolite conversion.
      Complementary studies were performed in rats cotreated with selective ERalpha- or
      ERbeta-antagonist. Hemodynamic and pulmonary artery (PA) and right ventricular
      (RV) remodeling parameters, including cell proliferation, cell cycle, and
      autophagy, were measured in vivo and in cultured primary rat PA endothelial
      cells. MEASUREMENTS AND MAIN RESULTS: E2 significantly attenuated HPH endpoints.
      Hypoxia increased ERbeta but not ERalpha lung vascular expression. Co-treatment
      with nonselective ER inhibitor or ERalpha-specific antagonist rendered hypoxic
      animals resistant to the beneficial effects of E2 on cardiopulmonary
      hemodynamics, whereas ERalpha- and ERbeta-specific antagonists opposed the
      remodeling effects of E2. In contrast, inhibition of E2-metabolite conversion did
      not abolish E2 protection. E2-treated hypoxic animals exhibited reduced ERK1/2
      activation and increased expression of cell-cycle inhibitor p27(Kip1) in lungs
      and RV, with up-regulation of lung autophagy. E2-induced signaling was
      recapitulated in hypoxic but not normoxic endothelial cells, and was associated
      with decreased vascular endothelial growth factor secretion and cell
      proliferation. CONCLUSIONS: E2 attenuates hemodynamic and remodeling parameters
      in HPH in an ER-dependent manner, through direct antiproliferative mechanisms on
      vascular cells, which may provide novel nonhormonal therapeutic targets for HPH.

PMID- 22383503
TI  - Sex-based comparisons of myofibrillar protein synthesis after resistance exercise
      in the fed state.
AB  - We made sex-based comparisons of rates of myofibrillar protein synthesis (MPS)
      and anabolic signaling after a single bout of high-intensity resistance exercise.
      Eight men (20 +/- 10 yr, BMI = 24.3 +/- 2.4) and eight women (22 +/- 1.8 yr, BMI
      = 23.0 +/- 1.9) underwent primed constant infusions of l-[ring
      (13)C(6)]phenylalanine on consecutive days with serial muscle biopsies. Biopsies
      were taken from the vastus lateralis at rest and 1, 3, 5, 24, 26, and 28 h after
      exercise. Twenty-five grams of whey protein was ingested immediately and 26 h
      after exercise. We also measured exercise-induced serum testosterone because it
      is purported to contribute to increases in myofibrillar protein synthesis (MPS)
      postexercise and its absence has been hypothesized to attenuate adaptative
      responses to resistance exercise in women. The exercise-induced area under the
      testosterone curve was 45-fold greater in men than women in the early (1 h)
      recovery period following exercise (P < 0.001). MPS was elevated similarly in men
      and women (2.3- and 2.7-fold, respectively) 1-5 h postexercise and after protein
      ingestion following 24 h recovery. Phosphorylation of mTOR(Ser2448) was elevated
      to a greater extent in men than women acutely after exercise (P = 0.003), whereas
      increased phosphorylation of p70S6K1(Thr389) was not different between sexes.
      Androgen receptor content was greater in men (main effect for sex, P = 0.049).
      Atrogin-1 mRNA abundance was decreased after 5 h recovery in both men and women
      (P < 0.001), and MuRF-1 expression was elevated in men after protein ingestion
      following 24 h recovery (P = 0.003). These results demonstrate minor sex-based
      differences in signaling responses and no difference in the MPS response to
      resistance exercise in the fed state. Interestingly, our data demonstrate that
      exercise-induced increases in MPS are dissociated from postexercise
      testosteronemia and that stimulation of MPS occurs effectively with low systemic
      testosterone concentrations in women.

PMID- 22383504
TI  - Are all airways equal?

PMID- 22383505
TI  - Monitoring in vivo changes in lung microstructure with 3He MRI in Sendai virus
      infected mice.
AB  - Recently, a Sendai virus (SeV) model of chronic obstructive lung disease has
      demonstrated an innate immune response in mouse airways that exhibits
      similarities to the chronic airway inflammation in human chronic obstructive
      pulmonary disease (COPD) and asthma, but the effect on distal lung parenchyma has
      not been investigated. The aim of our study is to image the time course and
      regional distribution of mouse lung microstructural changes in vivo after SeV
      infection. (1)H and (3)He diffusion magnetic resonance imaging (MRI) were
      successfully performed on five groups of C57BL/6J mice. (1)H MR images provided
      precise anatomical localization and lung volume measurements. (3)He lung
      morphometry was implemented to image and quantify mouse lung geometric
      microstructural parameters at different time points after SeV infection. (1)H MR
      images detected the SeV-induced pulmonary inflammation in vivo; spatially
      resolved maps of acinar airway radius R, alveolar depth h, and mean linear
      intercept Lm were generated from (3)He diffusion images. The morphometric
      parameters R and Lm in the infected group were indistinguishable from PBS-treated
      mice at day 21, increased slightly at day 49, and were increased with statistical
      significance at day 77 (p = 0.02). Increases in R and Lm of infected mice imply
      that there is a modest increase in alveolar duct radius distal to airway
      inflammation, particularly in the lung periphery, indicating airspace enlargement
      after virus infection. Our results indicate that (3)He lung morphometry has good
      sensitivity in quantifying small microstructural changes in the mouse lung and
      that the Sendai mouse model has the potential to be a valid murine model of COPD.

PMID- 22383506
TI  - Two-year citations of JAPPL original articles: evidence of a relative age effect.
AB  - Several indicators have been used to analyze scientific journals, with the impact
      factor and the number of citations in a 2-yr calendar time frame (2-YRC) being
      the most common factors. However, considering that the Journal of Applied
      Physiology (JAPPL) appears monthly and that calculations of these indicators are
      based on citations of papers published in previous years, we hypothesized that
      articles published at the beginning of the year would be cited more in the 2-YRC
      compared with those appearing in the last issues of the year, a phenomena known
      as a relative age effect. Our objective was to confirm the existence of a
      relative age effect in the 2-YRC for original articles published in JAPPL. From
      2005 to 2008, a total of 1,726 original articles were published, according to the
      Web of Science, and 9,973 citations in 2-YRC, varying from 0 to 45, with a mean
      of 5.78 for individual papers. Although there were no differences in the number
      of original articles published in a given month (P = 0.99), the 2-YRC varied
      considerably throughout the year, being higher for those earlier issues of the
      year, as shown by the linear regression analysis (r(2) = 0.76; P < 0.001). The 2
      YRC began at 6.62 during the first 3 mo of the year, dropping by 10% at each 3-mo
      period. In summary, the longer an article has been out there, the more citations
      it collects. The relative age effect is a potential confounding variable for the
      assessment and interpretation of 2-YRC (using calendar years) from JAPPL original
      articles.

PMID- 22383507
TI  - Airway responsiveness depends on the diffusion rate of methacholine across the
      airway wall.
AB  - During methacholine challenge tests of airway responsiveness, it is invariably
      assumed that the administered dose of agonist is accurately reflected in the dose
      that eventually reaches the airway smooth muscle (ASM). However, agonist must
      traverse a variety of tissue obstacles to reach the ASM, during which the agonist
      is subjected to both enzymatic breakdown and removal by the bronchial and
      pulmonary circulations. This raises the possibility that a significant fraction
      of the deposited agonist may never actually make it to the ASM. To understand the
      nature of this effect, we measured the time course of changes in airway
      resistance elicited by various durations of methacholine aerosol in mice. We fit
      to these data a computational model of a dynamically contracting airway
      responding to agonist that diffuses through an airway compartment, thereby
      obtaining rate constants that reflect the diffusive barrier to methacholine. We
      found that these barriers can contribute significantly to the time course of
      airway narrowing, raising the important possibility that alterations in the
      diffusive barrier presented by the airway wall may play a role in pathologically
      altered airway responsiveness.

PMID- 22383508
TI  - Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling
      in human skin.
AB  - Local administration of ascorbic acid (Asc) at a supraphysiological concentration
      inhibits the cutaneous vasoconstrictor response to local cooling (LC). However,
      whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response
      remains unknown. The purpose of the present study was to examine the acute
      influence of oral Asc on the adrenergic vasoconstrictor response to LC in human
      skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler
      flowmetry at three sites (forearm, calf, palm). The three skin sites were locally
      cooled from 34 to 24 degrees C at -1 degrees C/min and maintained at 24 degrees C
      for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or
      placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as
      the ratio of SkBF to blood pressure and expressed relative to the baseline value
      before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm
      (Pre, -50.3 +/- 3.3%; Post, -57.8 +/- 2.2%), calf (Pre, -52.6 +/- 3.7%; Post, 
      66.1 +/- 4.3%), and palm (Pre, -46.2 +/- 6.2%; Post, -60.4 +/- 5.6%) during LC.
      The placebo did not change the responses at any site. In experiment 2, to examine
      whether the increased vasoconstrictor response caused by oral Asc is due to the
      adrenergic system, the release of neurotransmitters from adrenergic nerves in
      forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT).
      Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but
      did not change the responses at BT-treated sites during LC. In experiment 3, to
      further examine whether adrenergically mediated vasoconstriction is enhanced by
      oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the
      forearm skin at 34 degrees C in the Pre and Post periods. Oral Asc increased (P <
      0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc
      acutely enhances the cutaneous vasoconstrictor responses to LC through the
      modification of adrenergic sympathetic mechanisms.

PMID- 22383509
TI  - Effects of aging, and other bad behaviors.

PMID- 22383510
TI  - Maximal Na+-K+-ATPase activity is upregulated in association with muscle
      activity.

PMID- 22383512
TI  - Psychological aspects of chronic health conditions.

PMID- 22383511
TI  - Unloading stress disturbs muscle regeneration through perturbed recruitment and
      function of macrophages.
AB  - Skeletal muscle is one of the most sensitive tissues to mechanical loading, and
      unloading inhibits the regeneration potential of skeletal muscle after injury.
      This study was designed to elucidate the specific effects of unloading stress on
      the function of immunocytes during muscle regeneration after injury. We examined
      immunocyte infiltration and muscle regeneration in cardiotoxin (CTX)-injected
      soleus muscles of tail-suspended (TS) mice. In CTX-injected TS mice, the cross
      sectional area of regenerating myofibers was smaller than that of weight-bearing
      (WB) mice, indicating that unloading delays muscle regeneration following CTX
      induced skeletal muscle damage. Delayed infiltration of macrophages into the
      injured skeletal muscle was observed in CTX-injected TS mice. Neutrophils and
      macrophages in CTX-injected TS muscle were presented over a longer period at the
      injury sites compared with those in CTX-injected WB muscle. Disturbance of
      activation and differentiation of satellite cells was also observed in CTX
      injected TS mice. Further analysis showed that the macrophages in soleus muscles
      were mainly Ly-6C-positive proinflammatory macrophages, with high expression of
      tumor necrosis factor-alpha and interleukin-1beta, indicating that unloading
      causes preferential accumulation and persistence of proinflammatory macrophages
      in the injured muscle. The phagocytic and myotube formation properties of
      macrophages from CTX-injected TS skeletal muscle were suppressed compared with
      those from CTX-injected WB skeletal muscle. We concluded that the disturbed
      muscle regeneration under unloading is due to impaired macrophage function,
      inhibition of satellite cell activation, and their cooperation.

PMID- 22383514
TI  - Intellectual disability (mental retardation).

PMID- 22383515
TI  - Encephalitis in the pediatric population.

PMID- 22383516
TI  - Index of Suspicion. Case 1: Irritability and signs of peritonitis in a neonate.
      Case 2: Red eye, excessive tearing, photophobia, irritability, and splenomegaly
      in an infant. Case 3: 2-year-old girl who has cough, right pulmonary
      abnormalities.

PMID- 22383517
TI  - Conflict resolution during adolescence.

PMID- 22383518
TI  - A male infant who has a white hair tuft and hypopigmented macules.

PMID- 22383519
TI  - Translational physiology: understanding the WHI gap.

PMID- 22383522
TI  - Identification of small molecule proliferating cell nuclear antigen (PCNA)
      inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA
      replication.
AB  - We have discovered that 3,3',5-triiodothyronine (T3) inhibits binding of a PIP
      box sequence peptide to proliferating cell nuclear antigen (PCNA) protein by
      competing for the same binding site, as evidenced by the co-crystal structure of
      the PCNA-T3 complex at 2.1 A resolution. Based on this observation, we have
      designed a novel, non-peptide small molecule PCNA inhibitor, T2 amino alcohol
      (T2AA), a T3 derivative that lacks thyroid hormone activity. T2AA inhibited
      interaction of PCNA/PIP-box peptide with an IC(50) of ~1 MUm and also PCNA and
      full-length p21 protein, the tightest PCNA ligand protein known to date. T2AA
      abolished interaction of PCNA and DNA polymerase delta in cellular chromatin. De
      novo DNA synthesis was inhibited by T2AA, and the cells were arrested in S-phase.
      T2AA inhibited growth of cancer cells with induction of early apoptosis.
      Concurrently, Chk1 and RPA32 in the chromatin are phosphorylated, suggesting that
      T2AA causes DNA replication stress by stalling DNA replication forks. T2AA
      significantly inhibited translesion DNA synthesis on a cisplatin-cross-linked
      template in cells. When cells were treated with a combination of cisplatin and
      T2AA, a significant increase in phospho(Ser(139))histone H2AX induction and cell
      growth inhibition was observed.

PMID- 22383521
TI  - Ubiquitination of BST-2 protein by HIV-1 Vpu protein does not require lysine,
      serine, or threonine residues within the BST-2 cytoplasmic domain.
AB  - The cellular protein BST-2/CD317/Tetherin has been shown to inhibit the release
      of HIV-1 and other enveloped viruses from infected cells. The HIV-1 accessory
      protein Vpu binds to both BST-2 and betaTrCP, a substrate-recognition subunit for
      the SCF (Skip1-Cullin1-F-box protein) E3 ubiquitin ligase complex. This
      interaction leads to both the degradation of BST-2 and the enhancement of viral
      egress. Recently BST-2 was shown to be ubiquitinated in this process. Here we
      have confirmed the Vpu- and betaTrCP-dependent multi/polyubiquitination of BST-2.
      Ubiquitinated BST-2 accumulated in cells treated with a lysosomal inhibitor but
      not a proteasomal inhibitor. Additionally, we observed that a BST-2 mutant
      deleted for its cytosolically exposed lysine residues is also ubiquitinated.
      Subsequent experiments suggested that Vpu promotes BST-2 ubiquitination upon
      amino acid residues bearing hydroxyl- but not thiol-bearing side chains. However,
      a BST-2 mutant bearing substitutions for its cytoplasmically exposed Ser, Thr,
      and Lys residues was still down-regulated, ubiquitinated, and degraded in a Vpu
      dependent manner. Our results suggest that Vpu may target either the BST-2
      cytoplasmic Tyr residues or the NH(2) terminus itself for ubiquitination.

PMID- 22383523
TI  - Human mitochondrial DNA helicase TWINKLE is both an unwinding and annealing
      helicase.
AB  - TWINKLE is a nucleus-encoded human mitochondrial (mt)DNA helicase. Point
      mutations in TWINKLE are associated with heritable neuromuscular diseases
      characterized by deletions in the mtDNA. To understand the biochemical basis of
      these diseases, it is important to define the roles of TWINKLE in mtDNA
      metabolism by studying its enzymatic activities. To this end, we purified native
      TWINKLE from Escherichia coli. The recombinant TWINKLE assembles into hexamers
      and higher oligomers, and addition of MgUTP stabilizes hexamers over higher
      oligomers. Probing into the DNA unwinding activity, we discovered that the
      efficiency of unwinding is greatly enhanced in the presence of a heterologous
      single strand-binding protein or a single-stranded (ss) DNA that is complementary
      to the unwound strand. We show that TWINKLE, although a helicase, has an
      antagonistic activity of annealing two complementary ssDNAs that interferes with
      unwinding in the absence of gp2.5 or ssDNA trap. Furthermore, only ssDNA and not
      double-stranded (ds)DNA competitively inhibits the annealing activity, although
      both DNAs bind with high affinities. This implies that dsDNA binds to a site that
      is distinct from the ssDNA-binding site that promotes annealing. Fluorescence
      anisotropy competition binding experiments suggest that TWINKLE has more than one
      ssDNA-binding sites, and we speculate that a surface-exposed ssDNA-specific site
      is involved in catalyzing DNA annealing. We propose that the strand annealing
      activity of TWINKLE may play a role in recombination-mediated replication
      initiation found in the mitochondria of mammalian brain and heart or in
      replication fork regression during repair of damaged DNA replication forks.

PMID- 22383524
TI  - Frequent incorporation of ribonucleotides during HIV-1 reverse transcription and
      their attenuated repair in macrophages.
AB  - Macrophages are well known long-lived reservoirs of HIV-1. Unlike activated
      CD4(+) T cells, this nondividing HIV-1 target cell type contains a very low level
      of the deoxynucleoside triphosphates (dNTPs) required for proviral DNA synthesis
      whereas the ribonucleoside triphosphate (rNTP) levels remain in the millimolar
      range, resulting in an extremely low dNTP/rNTP ratio. Biochemical simulations
      demonstrate that HIV-1 reverse transcriptase (RT) efficiently incorporates
      ribonucleoside monophosphates (rNMPs) during DNA synthesis at this ratio,
      predicting frequent rNMP incorporation by the virus specifically in macrophages.
      Indeed, HIV-1 RT incorporates rNMPs at a remarkable rate of 1/146 nucleotides
      during macrophage infection. This greatly exceeds known rates for cellular
      replicative polymerases. In contrast, little or no rNMP incorporation is detected
      in CD4(+) T cells. Repair of these rNMP lesions is also substantially delayed in
      macrophages compared with CD4(+) T cells. Single rNMPs embedded in a DNA template
      are known to induce cellular DNA polymerase pausing, which mechanistically
      contributes to mutation synthesis. Indeed, we also observed that embedded rNMPs
      in a dsDNA template also induce HIV-1 RT DNA synthesis pausing. Moreover,
      unrepaired rNMPs incorporated into the provirus during HIV-1 reverse
      transcription would be generally mutagenic as was shown in Saccharomyces
      cerevisiae. Most importantly, the frequent incorporation of rNMPs makes them an
      ideal candidate for development of a new class of HIV RT inhibitors.

PMID- 22383525
TI  - Low-density lipoprotein receptor represents an apolipoprotein E-independent
      pathway of Abeta uptake and degradation by astrocytes.
AB  - Accumulation of the amyloid beta (Abeta) peptide within the brain is hypothesized
      to be one of the main causes underlying the pathogenic events that occur in
      Alzheimer disease (AD). Consequently, identifying pathways by which Abeta is
      cleared from the brain is crucial for better understanding of the disease
      pathogenesis and developing novel therapeutics. Cellular uptake and degradation
      by glial cells is one means by which Abeta may be cleared from the brain. In the
      current study, we demonstrate that modulating levels of the low-density
      lipoprotein receptor (LDLR), a cell surface receptor that regulates the amount of
      apolipoprotein E (apoE) in the brain, altered both the uptake and degradation of
      Abeta by astrocytes. Deletion of LDLR caused a decrease in Abeta uptake, whereas
      increasing LDLR levels significantly enhanced both the uptake and clearance of
      Abeta. Increasing LDLR levels also enhanced the cellular degradation of Abeta and
      facilitated the vesicular transport of Abeta to lysosomes. Despite the fact that
      LDLR regulated the uptake of apoE by astrocytes, we found that the effect of LDLR
      on Abeta uptake and clearance occurred in the absence of apoE. Finally, we
      provide evidence that Abeta can directly bind to LDLR, suggesting that an
      interaction between LDLR and Abeta could be responsible for LDLR-mediated Abeta
      uptake. Therefore, these results identify LDLR as a receptor that mediates Abeta
      uptake and clearance by astrocytes, and provide evidence that increasing glial
      LDLR levels may promote Abeta degradation within the brain.

PMID- 22383526
TI  - Yeast mitochondrial leucyl-tRNA synthetase CP1 domain has functionally diverged
      to accommodate RNA splicing at expense of hydrolytic editing.
AB  - The yeast mitochondrial leucyl-tRNA synthetase (ymLeuRS) performs dual essential
      roles in group I intron splicing and protein synthesis. A specific LeuRS domain
      called CP1 is responsible for clearing noncognate amino acids that are
      misactivated during aminoacylation. The ymLeuRS CP1 domain also plays a critical
      role in splicing. Herein, the ymLeuRS CP1 domain was isolated from the full
      length enzyme and was active in RNA splicing in vitro. Unlike its Escherichia
      coli LeuRS CP1 domain counterpart, it failed to significantly hydrolyze
      misaminoacylated tRNA(Leu). In addition and in stark contrast to the yeast
      domain, the editing-active E. coli LeuRS CP1 domain failed to recapitulate the
      splicing activity of the full-length E. coli enzyme. Although LeuRS-dependent
      splicing activity is rooted in an ancient adaptation for its aminoacylation
      activity, these results suggest that the ymLeuRS has functionally diverged to
      confer a robust splicing activity. This adaptation could have come at some
      expense to the protein's housekeeping role in aminoacylation and editing.

PMID- 22383527
TI  - Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase.
AB  - The Rho GTPase Rac regulates actin cytoskeleton reorganization to form cell
      surface extensions (lamellipodia) required for cell migration/invasion during
      cancer metastasis. Rac hyperactivation and overexpression are associated with
      aggressive cancers; thus, interference of the interaction of Rac with its direct
      upstream activators, guanine nucleotide exchange factors (GEFs), is a viable
      strategy for inhibiting Rac activity. We synthesized EHop-016, a novel inhibitor
      of Rac activity, based on the structure of the established Rac/Rac GEF inhibitor
      NSC23766. Herein, we demonstrate that EHop-016 inhibits Rac activity in the MDA
      MB-435 metastatic cancer cells that overexpress Rac and exhibits high endogenous
      Rac activity. The IC(50) of 1.1 MUM for Rac inhibition by EHop-016 is ~100-fold
      lower than for NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations
      of <=5 MUM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42.
      In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop
      016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A), which has
      a high affinity for activated GEFs. EHop-016 also inhibits the Rac activity of
      MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia
      formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1
      (p21-activated kinase 1) activity and directed migration of metastatic cancer
      cells. Moreover, at effective concentrations (<5 MUM), EHop-016 does not affect
      the viability of transformed mammary epithelial cells (MCF-10A) and reduces
      viability of MDA-MB-435 cells by only 20%. Therefore, EHop-016 holds promise as a
      targeted therapeutic agent for the treatment of metastatic cancers with high Rac
      activity.

PMID- 22383528
TI  - Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up
      regulation of Hyaluronan synthase 2 through decreased ceramide production and
      activation of Akt.
AB  - Fibroblasts from the fro/fro mouse, with a deletion in the Smpd3 gene coding for
      the active site of neutral sphingomyelinase 2 (NSMase2), secreted increased
      amounts of hyaluronan (HA). This was reversed by transfection with the Smpd3
      gene, suggesting a connection between sphingolipid and glycosaminoglycan
      metabolism. The deficiency of NSMase2 resulted in storage of sphingomyelin (SM)
      and cholesterol with a 50% reduction in ceramides (Cer). RT-PCR and Western blot
      analysis showed that increased HA secretion resulted from increased hyaluronan
      synthase 2 (HAS2) activity localized to sphingolipid-enriched lipid rafts.
      Although cholesterol levels were also elevated in lipid rafts from mouse
      fibroblasts deficient in lysosomal acid SMase activity (deletion of the Smpd1(-/
      ) gene), there was no increase in HA secretion. We then showed that in fro/fro
      fibroblasts, the reduced ceramide was associated with decreased phosphorylation
      of protein phosphatase 2A (PP2A) and increased phosphorylation of its substrate
      Akt-p, together with PI3K, PDK1, mTOR (mammalian target of rapamycin), and
      p70S6K, although PTEN was unaffected. Exogenous ceramide, as well as inhibitors
      of Akt (Akt inhibitor VIII), PI 3-kinase (LY294002 and wortmannin), and mTOR
      (rapamycin) reduced secretion of HA, whereas the NSMase2 inhibitor GW4869
      increased HA synthesis and secretion. We propose that NSMase2/Cer are the key
      mediators of the regulation of HA synthesis, via microdomains and the Akt/mTOR
      pathway.

PMID- 22383529
TI  - G Protein-regulated inducer of neurite outgrowth (GRIN) modulates Sprouty protein
      repression of mitogen-activated protein kinase (MAPK) activation by growth factor
      stimulation.
AB  - Galpha(o/i) interacts directly with GRIN (G protein-regulated inducer of neurite
      outgrowth). Using the yeast two-hybrid system, we identified Sprouty2 as an
      interacting partner of GRIN. Galpha(o) and Sprouty2 bind to overlapping regions
      of GRIN, thus competing for GRIN binding. Imaging experiments demonstrated that
      Galpha(o) expression promoted GRIN translocation to the plasma membrane, whereas
      Sprouty2 expression failed to do so. Given the role of Sprouty2 in the regulation
      of growth factor-mediated MAPK activation, we examined the contribution of the
      GRIN-Sprouty2 interaction to CB1 cannabinoid receptor regulation of FGF receptor
      signaling. In Neuro-2A cells, a system that expresses all of the components
      endogenously, modulation of GRIN levels led to regulation of MAPK activation.
      Overexpression of GRIN potentiated FGF activation of MAPK and decreased tyrosine
      phosphorylation of Sprouty2. Pretreatment with G(o/i)-coupled CB1 receptor
      agonist attenuated subsequent FGF activation of MAPK. Decreased expression of
      GRIN both diminished FGF activation of MAPK and blocked CB1R attenuation of MAPK
      activation. These observations indicate that Galpha(o) interacts with GRIN and
      outcompetes GRIN from bound Sprouty. Free Sprouty then in turn inhibits growth
      factor signaling. Thus, here we present a novel mechanism of how G(o/i)-coupled
      receptors can inhibit growth factor signaling to MAPK.

PMID- 22383530
TI  - Calcium-myristoyl Tug is a new mechanism for intramolecular tuning of calcium
      sensitivity and target enzyme interaction for guanylyl cyclase-activating protein
      1: dynamic connection between N-fatty acyl group and EF-hand controls calcium
      sensitivity.
AB  - Guanylyl cyclase-activating protein 1 (GCAP1), a myristoylated Ca(2+) sensor in
      vision, regulates retinal guanylyl cyclase (RetGC). We show that protein
      myristoyl group interactions control Ca(2+) sensitivity, apparent affinity for
      RetGC, and maximal level of cyclase activation. Mutating residues near the
      myristoyl moiety affected the affinity of Ca(2+) binding to EF-hand 4. Inserting
      Phe residues in the cavity around the myristoyl group increased both the affinity
      of GCAP1 for RetGC and maximal activation of the cyclase. NMR spectra show that
      the myristoyl group in the L80F/L176F/V180F mutant remained sequestered inside
      GCAP1 in both Ca(2+)-bound and Mg(2+)-bound states. This mutant displayed much
      higher affinity for the cyclase but reduced Ca(2+) sensitivity of the cyclase
      regulation. The L176F substitution improved affinity of myristoylated and non
      acylated GCAP1 for the cyclase but simultaneously reduced the affinity of Ca(2+)
      binding to EF-hand 4 and Ca(2+) sensitivity of the cyclase regulation by acylated
      GCAP1. The replacement of amino acids near both ends of the myristoyl moiety
      (Leu(80) and Val(180)) minimally affected regulatory properties of GCAP1. N
      Lauryl- and N-myristoyl-GCAP1 activated RetGC in a similar fashion. Thus, protein
      interactions with the central region of the fatty acyl chain optimize GCAP1
      binding to RetGC and maximize activation of the cyclase. We propose a dynamic
      connection (or "tug") between the fatty acyl group and EF-hand 4 via the C
      terminal helix that attenuates the efficiency of RetGC activation in exchange for
      optimal Ca(2+) sensitivity.

PMID- 22383532
TI  - REvolver: modeling sequence evolution under domain constraints.
AB  - Simulating the change of protein sequences over time in a biologically realistic
      way is fundamental for a broad range of studies with a focus on evolution. It is,
      thus, problematic that typically simulators evolve individual sites of a sequence
      identically and independently. More realistic simulations are possible; however,
      they are often prohibited by limited knowledge concerning site-specific
      evolutionary constraints or functional dependencies between amino acids. As a
      consequence, a protein's functional and structural characteristics are rapidly
      lost in the course of simulated evolution. Here, we present REvolver
      (www.cibiv.at/software/revolver), a program that simulates protein sequence
      alteration such that evolutionarily stable sequence characteristics, like
      functional domains, are maintained. For this purpose, REvolver recruits profile
      hidden Markov models (pHMMs) for parameterizing site-specific models of sequence
      evolution in an automated fashion. pHMMs derived from alignments of homologous
      proteins or protein domains capture information regarding which sequence sites
      remained conserved over time and where in a sequence insertions or deletions are
      more likely to occur. Thus, they describe constraints on the evolutionary process
      acting on these sequences. To demonstrate the performance of REvolver as well as
      its applicability in large-scale simulation studies, we evolved the entire human
      proteome up to 1.5 expected substitutions per site. Simultaneously, we analyzed
      the preservation of Pfam and SMART domains in the simulated sequences over time.
      REvolver preserved 92% of the Pfam domains originally present in the human
      sequences. This value drops to 15% when traditional models of amino acid sequence
      evolution are used. Thus, REvolver represents a significant advance toward a
      realistic simulation of protein sequence evolution on a proteome-wide scale.
      Further, REvolver facilitates the simulation of a protein family with a user
      defined domain architecture at the root.

PMID- 22383531
TI  - Evolution of siglec-11 and siglec-16 genes in hominins.
AB  - We previously reported a human-specific gene conversion of SIGLEC11 by an
      adjacent paralogous pseudogene (SIGLEC16P), generating a uniquely human form of
      the Siglec-11 protein, which is expressed in the human brain. Here, we show that
      Siglec-11 is expressed exclusively in microglia in all human brains studied-a
      finding of potential relevance to brain evolution, as microglia modulate neuronal
      survival, and Siglec-11 recruits SHP-1, a tyrosine phosphatase that modulates
      microglial biology. Following the recent finding of a functional SIGLEC16 allele
      in human populations, further analysis of the human SIGLEC11 and SIGLEC16/P
      sequences revealed an unusual series of gene conversion events between two loci.
      Two tandem and likely simultaneous gene conversions occurred from SIGLEC16P to
      SIGLEC11 with a potentially deleterious intervening short segment happening to be
      excluded. One of the conversion events also changed the 5' untranslated sequence,
      altering predicted transcription factor binding sites. Both of the gene
      conversions have been dated to ~1-1.2 Ma, after the emergence of the genus Homo,
      but prior to the emergence of the common ancestor of Denisovans and modern humans
      about 800,000 years ago, thus suggesting involvement in later stages of hominin
      brain evolution. In keeping with this, recombinant soluble Siglec-11 binds
      ligands in the human brain. We also address a second-round more recent gene
      conversion from SIGLEC11 to SIGLEC16, with the latter showing an allele frequency
      of ~0.1-0.3 in a worldwide population study. Initial pseudogenization of SIGLEC16
      was estimated to occur at least 3 Ma, which thus preceded the gene conversion of
      SIGLEC11 by SIGLEC16P. As gene conversion usually disrupts the converted gene,
      the fact that ORFs of hSIGLEC11 and hSIGLEC16 have been maintained after an
      unusual series of very complex gene conversion events suggests that these events
      may have been subject to hominin-specific selection forces.

PMID- 22383533
TI  - A high-throughput panel for identifying clinically relevant mutation profiles in
      melanoma.
AB  - Success with molecular-based targeted drugs in the treatment of cancer has
      ignited extensive research efforts within the field of personalized therapeutics.
      However, successful application of such therapies is dependent on the presence or
      absence of mutations within the patient's tumor that can confer clinical efficacy
      or drug resistance. Building on these findings, we developed a high-throughput
      mutation panel for the identification of frequently occurring and clinically
      relevant mutations in melanoma. An extensive literature search and interrogation
      of the Catalogue of Somatic Mutations in Cancer database identified more than
      1,000 melanoma mutations. Applying a filtering strategy to focus on mutations
      amenable to the development of targeted drugs, we initially screened 120 known
      mutations in 271 samples using the Sequenom MassARRAY system. A total of 252
      mutations were detected in 17 genes, the highest frequency occurred in BRAF (n =
      154, 57%), NRAS (n = 55, 20%), CDK4 (n = 8, 3%), PTK2B (n = 7, 2.5%), and ERBB4
      (n = 5, 2%). Based on this initial discovery screen, a total of 46 assays
      interrogating 39 mutations in 20 genes were designed to develop a melanoma
      specific panel. These assays were distributed in multiplexes over 8 wells using
      strict assay design parameters optimized for sensitive mutation detection. The
      final melanoma-specific mutation panel is a cost effective, sensitive, high
      throughput approach for identifying mutations of clinical relevance to molecular
      based therapeutics for the treatment of melanoma. When used in a clinical
      research setting, the panel may rapidly and accurately identify potentially
      effective treatment strategies using novel or existing molecularly targeted
      drugs.

PMID- 22383536
TI  - Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition
      state.
AB  - Mitogen-activated protein kinase kinase 6 (MAP2K6) plays a crucial role in the
      p38 MAP kinase signal cascade that regulates various stress-induced responses and
      is associated with pathological conditions. The crystal structure of human non
      phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at
      2.6 A resolution and represents an auto-inhibition state of MAP2K6. Three
      characteristics of short alpha-helices configured in the activation loop region,
      termed activation helices (AH1, AH2 and AH3), are important in controlling the
      auto-inhibition mechanism. AH1 displaces the alphaC-helix, a component essential
      for forming the active configuration, away from the active site. AH1 and AH2 were
      found to enclose the gamma-phosphate, the leaving group of ATP. A comparison with
      the related enzymes, MAP2K1 and MAP2K4 reveals that MAP2K6 has the unique auto
      inhibition mechanism mediated by the three activation helices.

PMID- 22383537
TI  - Smad7-deficient mice show growth retardation with reduced viability.
AB  - Smad7 is an inhibitory molecule induced by members of the transforming growth
      factor-beta (TGF-beta) family, including TGF-beta, activin, nodal and bone
      morphogenetic proteins (BMPs). To elucidate the in vivo functions of Smad7, we
      generated conditional Smad7-knockout mice in which the Mad homology 2 (MH2)
      domain and the poly (A) signal sequence were flanked with loxP sites (floxed).
      The Smad7-floxed mice exhibited no obvious phenotype. Smad7 total-null mice on a
      C57BL/6 background died within a few days of birth, whereas mice with an ICR
      background developed to adulthood but were significantly smaller than wild-type
      mice. Unexpectedly, phospho-Smad2 and phospho-Smad3 were decreased in Smad7
      deficient mouse embryonic fibroblast (MEF) cells, whereas phospho-Smad1/5/8 was
      similarly expressed in wild-type and Smad7-deficient MEF cells. Moreover,
      expression levels of TGF-beta type I receptor (ALK5) were higher in Smad7
      deficient MEF cells than in wild-type MEF cells. Plasminogen activator inhibitor
      1 (PAI-1) and inhibitor of differentiation-1 (Id-1) mRNA were similarly expressed
      in wild-type and Smad7-deficient MEF cells. Some differences were observed in
      mitogen-activated protein kinase (MAPK)-signalling between wild-type and Smad7
      deficient MEF cells. We demonstrated that Smad7 plays an important role in normal
      mouse growth and provide a useful tool for analysing Smad7 functions in vivo.

PMID- 22383538
TI  - Effects of phosphatase and proteasome inhibitors on Borealin phosphorylation and
      degradation.
AB  - The chromosomal passenger complex (CPC) senses tension defects at the kinetochore
      to activate the spindle assembly checkpoint, and helps to position the cleavage
      furrow. The CPC, consisting of INCENP, Survivin, Borealin and Aurora B localizes
      to the inner centromere at metaphase and re-localizes to the spindle midzone at
      anaphase; several CPC functions are regulated by post-translational modification.
      Borealin is phosphorylated at multiple sites and phosphorylation at S219 causes
      Borealin to migrate more slowly upon electrophoresis. Here we find that Cdk1 can
      induce a mobility shift of Borealin, suggesting that S219 phosphorylation is
      under Cdk1 control. However, Cdk1 is inefficient at phosphorylating purified
      Borealin in vitro. A yeast orthologue of Borealin, Npl1, is dephosphorylated by
      the phosphatase Cdc14. We find no difference in the mobility shift of Borealin in
      human cells lacking either Cdc14A or Cdc14B. In contrast, the phosphatase
      inhibitor okadaic acid does delay the dephosphorylation of Borealin as cells exit
      mitosis. The proteasome inhibitor MG132 reduces Borealin phosphorylation in
      mitosis and increases the steady-state level of Borealin, especially in mutants
      lacking the C-terminus. However, a second, structurally unrelated proteasome
      inhibitor, lactacystin did not up-regulate Borealin. These results suggest that
      the effect of MG132 on Borealin is due to the inhibition of an intracellular
      protease other than the proteasome.

PMID- 22383539
TI  - Plastids are major regulators of light signaling in Arabidopsis.
AB  - We previously provided evidence that plastid signaling regulates the downstream
      components of a light signaling network and that this signal integration
      coordinates chloroplast biogenesis with both the light environment and
      development by regulating gene expression. We tested these ideas by analyzing
      light- and plastid-regulated transcriptomes in Arabidopsis (Arabidopsis
      thaliana). We found that the enrichment of Gene Ontology terms in these
      transcriptomes is consistent with the integration of light and plastid signaling
      (1) down-regulating photosynthesis and inducing both repair and stress tolerance
      in dysfunctional chloroplasts and (2) helping coordinate processes such as
      growth, the circadian rhythm, and stress responses with the degree of chloroplast
      function. We then tested whether factors that contribute to this signal
      integration are also regulated by light and plastid signals by characterizing T
      DNA insertion alleles of genes that are regulated by light and plastid signaling
      and that encode proteins that are annotated as contributing to signaling,
      transcription, or no known function. We found that a high proportion of these
      mutant alleles induce chloroplast biogenesis during deetiolation. We quantified
      the expression of four photosynthesis-related genes in seven of these enhanced
      deetiolation (end) mutants and found that photosynthesis-related gene expression
      is attenuated. This attenuation is particularly striking for Photosystem II
      subunit S expression. We conclude that the integration of light and plastid
      signaling regulates a number of END genes that help optimize chloroplast function
      and that at least some END genes affect photosynthesis-related gene expression.

PMID- 22383540
TI  - The U-Box/ARM E3 ligase PUB13 regulates cell death, defense, and flowering time
      in Arabidopsis.
AB  - The components in plant signal transduction pathways are intertwined and affect
      each other to coordinate plant growth, development, and defenses to stresses. The
      role of ubiquitination in connecting these pathways, particularly plant innate
      immunity and flowering, is largely unknown. Here, we report the dual roles for
      the Arabidopsis (Arabidopsis thaliana) Plant U-box protein13 (PUB13) in defense
      and flowering time control. In vitro ubiquitination assays indicated that PUB13
      is an active E3 ubiquitin ligase and that the intact U-box domain is required for
      the E3 ligase activity. Disruption of the PUB13 gene by T-DNA insertion results
      in spontaneous cell death, the accumulation of hydrogen peroxide and salicylic
      acid (SA), and elevated resistance to biotrophic pathogens but increased
      susceptibility to necrotrophic pathogens. The cell death, hydrogen peroxide
      accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when
      plants are pretreated with high humidity. Importantly, pub13 also shows early
      flowering under middle- and long-day conditions, in which the expression of
      SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and FLOWERING LOCUS T is induced while
      FLOWERING LOCUS C expression is suppressed. Finally, we found that two components
      involved in the SA-mediated signaling pathway, SID2 and PAD4, are required for
      the defense and flowering-time phenotypes caused by the loss of function of
      PUB13. Taken together, our data demonstrate that PUB13 acts as an important node
      connecting SA-dependent defense signaling and flowering time regulation in
      Arabidopsis.

PMID- 22383542
TI  - Patient safety culture and the association with safe resident care in nursing
      homes.
AB  - PURPOSE OF THE STUDY: Studies have shown that patient safety culture (PSC) is
      poorly developed in nursing homes (NHs), and, therefore, residents of NHs may be
      at risk of harm. Using Donabedian's Structure-Process-Outcome (SPO) model, we
      examined the relationships among top management's ratings of NH PSC, a process of
      care, and safety outcomes. DESIGN AND METHODS: Using top management's responses
      from a nationally representative sample of 3,557 NHs on the 2008 Nursing Home
      Survey on PSC, the Online Survey, Certification, and Reporting Database, and the
      Minimum Data Set, we examined the relationships among the three components of
      Donabedian's SPO model: structure (PSC), a process of care (physical restraints),
      and patient safety outcomes (residents who fell). RESULTS: Results from
      generalized estimating equations indicated that higher ratings of PSC were
      significantly related to lower prevalence of physical restraints (odds ratio [OR]
      = 0.997, 95% confidence interval [CI] = 0.995-0.999) and residents who fell (OR =
      0.999, 95% CI = 0.998-0.999). Physical restraint use was related to falls after
      controlling for structural characteristics and PSC (OR = 1.698, 95% CI = 1.619
      1.781). IMPLICATIONS: These findings can contribute to the development of PSC in
      NHs and promote improvements in health care that can be measured by process of
      care and resident outcomes.

PMID- 22383541
TI  - Characterization of genes involved in cytokinin signaling and metabolism from
      rice.
AB  - Two-component signaling elements play important roles in plants, including a
      central role in cytokinin signaling. We characterized two-component elements from
      the monocot rice (Oryza sativa) using several complementary approaches.
      Phylogenetic analysis reveals relatively simple orthologous relationships among
      the histidine kinases in rice and Arabidopsis (Arabidopsis thaliana). In
      contrast, the histidine-containing phosphotransfer proteins (OsHPs) and response
      regulators (OsRRs) display a higher degree of lineage-specific expansion. The
      intracellular localizations of several OsHPs and OsRRs were examined in rice and
      generally found to correspond to the localizations of their dicot counterparts.
      The functionality of rice type-B OsRRs was tested in Arabidopsis; one from a
      clade composed of both monocot and dicot type-B OsRRs complemented an Arabidopsis
      type-B response regulator mutant, but a type-B OsRR from a monocot-specific
      subfamily generally did not. The expression of genes encoding two-component
      elements and proteins involved in cytokinin biosynthesis and degradation was
      analyzed in rice roots and shoots and in response to phytohormones. Nearly all
      type-A OsRRs and OsHK4 were up-regulated in response to cytokinin, but other
      cytokinin signaling elements were not appreciably affected. Furthermore, multiple
      cytokinin oxidase (OsCKX) genes were up-regulated by cytokinin. Abscisic acid
      treatment decreased the expression of several genes involved in cytokinin
      biosynthesis and degradation. Auxin affected the expression of a few genes;
      brassinosteroid and gibberellin had only modest effects. Our results support a
      shared role for two-component elements in mediating cytokinin signaling in
      monocots and dicots and reveal how phytohormones can impact cytokinin function
      through modulating gene expression.

PMID- 22383543
TI  - Age-related hearing loss: quality of care for quality of life.
AB  - Age-related hearing loss (ARHL), known as presbycusis, is characterized by
      progressive deterioration of auditory sensitivity, loss of the auditory sensory
      cells, and central processing functions associated with the aging process. ARHL
      is the third most prevalent chronic condition in older Americans, after
      hypertension and arthritis, and is a leading cause of adult hearing handicaps in
      the United States. The prevalence of ARHL is expected to rise for the next
      several decades with the increasing aging Baby Boomer population. Nevertheless,
      ARHL remains an often undetected, underestimated and neglected condition in the
      geriatric population due to a slow development process of the disease. If left
      untreated, the impact of ARHL on patients, significant others, and the society as
      a whole would be significant. The purpose of this review is to raise the
      awareness of ARHL, to update our current understanding of ARHL with a focus on
      age-related deficits in auditory and cognitive processing of speech, and to
      explore strategies of prevention, identification, amplification, and aural
      rehabilitation. The ultimate goal is to improve the quality of hearing health
      care and the overall quality of life of the Baby Boomer generation.

PMID- 22383545
TI  - Clinical practice guideline: sudden hearing loss.
AB  - OBJECTIVE: Sudden hearing loss (SHL) is a frightening symptom that often prompts
      an urgent or emergent visit to a physician. This guideline provides evidence
      based recommendations for the diagnosis, management, and follow-up of patients
      who present with SHL. The guideline primarily focuses on sudden sensorineural
      hearing loss (SSNHL) in adult patients (aged 18 and older). Prompt recognition
      and management of SSNHL may improve hearing recovery and patient quality of life
      (QOL). Sudden sensorineural hearing loss affects 5 to 20 per 100,000 population,
      with about 4000 new cases per year in the United States. This guideline is
      intended for all clinicians who diagnose or manage adult patients who present
      with SHL. PURPOSE: The purpose of this guideline is to provide clinicians with
      evidence-based recommendations in evaluating patients with SHL, with particular
      emphasis on managing SSNHL. The panel recognized that patients enter the health
      care system with SHL as a nonspecific, primary complaint. Therefore, the initial
      recommendations of the guideline deal with efficiently distinguishing SSNHL from
      other causes of SHL at the time of presentation. By focusing on opportunities for
      quality improvement, the guideline should improve diagnostic accuracy, facilitate
      prompt intervention, decrease variations in management, reduce unnecessary tests
      and imaging procedures, and improve hearing and rehabilitative outcomes for
      affected patients. RESULTS: The panel made strong recommendations that clinicians
      should (1) distinguish sensorineural hearing loss from conductive hearing loss in
      a patient presenting with SHL; (2) educate patients with idiopathic sudden
      sensorineural hearing loss (ISSNHL) about the natural history of the condition,
      the benefits and risks of medical interventions, and the limitations of existing
      evidence regarding efficacy; and (3) counsel patients with incomplete recovery of
      hearing about the possible benefits of amplification and hearing-assistive
      technology and other supportive measures. The panel made recommendations that
      clinicians should (1) assess patients with presumptive SSNHL for bilateral SHL,
      recurrent episodes of SHL, or focal neurologic findings; (2) diagnose presumptive
      ISSNHL if audiometry confirms a 30-dB hearing loss at 3 consecutive frequencies
      and an underlying condition cannot be identified by history and physical
      examination; (3) evaluate patients with ISSNHL for retrocochlear pathology by
      obtaining magnetic resonance imaging, auditory brainstem response, or audiometric
      follow-up; (4) offer intratympanic steroid perfusion when patients have
      incomplete recovery from ISSNHL after failure of initial management; and (5)
      obtain follow-up audiometric evaluation within 6 months of diagnosis for patients
      with ISSNHL. The panel offered as options that clinicians may offer (1)
      corticosteroids as initial therapy to patients with ISSNHL and (2) hyperbaric
      oxygen therapy within 3 months of diagnosis of ISSNHL. The panel made a
      recommendation against clinicians routinely prescribing antivirals,
      thrombolytics, vasodilators, vasoactive substances, or antioxidants to patients
      with ISSNHL. The panel made strong recommendations against clinicians (1)
      ordering computerized tomography of the head/brain in the initial evaluation of a
      patient with presumptive SSNHL and (2) obtaining routine laboratory tests in
      patients with ISSNHL.

PMID- 22383546
TI  - Exploring the human genome, and relearning genetics by necessity.

PMID- 22383544
TI  - The expression profile of C19MC microRNAs in primary human trophoblast cells and
      exosomes.
AB  - The largest gene cluster of human microRNAs (miRNAs), the chromosome 19 miRNA
      cluster (C19MC), is exclusively expressed in the placenta and in undifferentiated
      cells. The precise expression pattern and function of C19MC members are unknown.
      We sought to profile the relative expression of C19MC miRNAs in primary human
      trophoblast (PHT) cells and exosomes. Using high-throughput profiling, confirmed
      by PCR, we found that C19MC miRNAs are among the most abundant miRNAs in term
      human trophoblasts. Hypoxic stress selectively reduced miR-520c-3p expression at
      certain time-points with no effect on other C19MC miRNAs. Similarly,
      differentiation in vitro had a negligible effect on C19MC miRNAs. We found that
      C19MC miRNAs are the predominant miRNA species expressed in exosomes released
      from PHT, resembling the profile of trophoblastic cellular miRNA. Predictably, we
      detected the similar levels of circulating C19MC miRNAs in the serum of healthy
      pregnant women at term and in women with pregnancies complicated by fetal growth
      restriction. Our data define the relative expression levels of C19MC miRNAs in
      trophoblasts and exosomes, and suggest that C19MC miRNAs function in placental
      maternal signaling.

PMID- 22383547
TI  - Cervical cancer screening (NOVEMBER 2011).

PMID- 22383548
TI  - Dabigatran (OCTOBER 2011).

PMID- 22383550
TI  - High creatinine 6 months after renal transplant.

PMID- 22383551
TI  - A 26-year-old woman with a lump in her chest.

PMID- 22383552
TI  - Putting genome analysis to good use: lessons from C-reactive protein and
      cardiovascular disease.
AB  - New methods of studying the human genome offer novel ways to examine the
      relationship between biomarkers and common, chronic human diseases. As an
      example, we will review a large genomics study (Elliott et al, JAMA 2009; 302:37
      48) that concluded that C-reactive protein (CRP) is likely not a cause of
      coronary heart disease, although it is a marker for it.

PMID- 22383554
TI  - Asthma in African Americans: what can we do about the higher rates of disease?
AB  - African Americans not only have a higher prevalence of asthma than whites, they
      also are encumbered with higher rates of asthma-associated morbidity and death.
      Factors such as genetics, socioeconomic status, health maintenance behaviors, air
      quality, and obesity likely contribute in combination to these burdens. Further
      work is needed to better understand these complex risk factors. To remedy these
      disparities, we need to ensure that patients at higher risk are given proper care
      and the knowledge to control their asthma.

PMID- 22383555
TI  - Endoscopic ultrasonography to evaluate pancreatitis.
AB  - Endoscopic ultrasonography (EUS) has become a well-accepted test in the workup of
      acute and chronic pancreatitis. However, further studies are needed to define its
      diagnostic role in patients with recurrent acute pancreatitis and minimal-change
      chronic pancreatitis.

PMID- 22383556
TI  - Update on contraceptive options: a case-based discussion.
AB  - As health care providers, we must engage our female patients in a dialogue about
      their contraceptive and fertility decisions. Empowering and educating our
      patients about their bodies' hormones, the menstrual cycle, and the risk of
      unintended pregnancy are central to effective contraceptive counseling. Selecting
      an appropriate method for a patient and her medical profile is rewarding and
      challenging in view of new medications, novel delivery systems, and evolving
      research.

PMID- 22383557
TI  - Protease inhibitors: silver bullets for chronic hepatitis C infection?
AB  - Recent trials evaluated the safety and efficacy of two protease inhibitors,
      boceprevir (Victrelis) and telaprevir (Incivek), added to standard care with
      pegylated interferon and ribavirin, in patients with chronic hepatitis C virus
      (HCV) infection. These drugs open the door for triple therapy and other new
      therapies involving combinations of other direct-acting antiviral agents to
      become the new standard of care for this population.

PMID- 22383559
TI  - Collaboration in social networks.
AB  - The very notion of social network implies that linked individuals interact
      repeatedly with each other. This notion allows them not only to learn successful
      strategies and adapt to them, but also to condition their own behavior on the
      behavior of others, in a strategic forward looking manner. Game theory of
      repeated games shows that these circumstances are conducive to the emergence of
      collaboration in simple games of two players. We investigate the extension of
      this concept to the case where players are engaged in a local contribution game
      and show that rationality and credibility of threats identify a class of Nash
      equilibria--that we call "collaborative equilibria"--that have a precise
      interpretation in terms of subgraphs of the social network. For large network
      games, the number of such equilibria is exponentially large in the number of
      players. When incentives to defect are small, equilibria are supported by local
      structures whereas when incentives exceed a threshold they acquire a nonlocal
      nature, which requires a "critical mass" of more than a given fraction of the
      players to collaborate. Therefore, when incentives are high, an individual
      deviation typically causes the collapse of collaboration across the whole system.
      At the same time, higher incentives to defect typically support equilibria with a
      higher density of collaborators. The resulting picture conforms with several
      results in sociology and in the experimental literature on game theory, such as
      the prevalence of collaboration in denser groups and in the structural hubs of
      sparse networks.

PMID- 22383560
TI  - The ancestral SgrS RNA discriminates horizontally acquired Salmonella mRNAs
      through a single G-U wobble pair.
AB  - SgrS RNA is a model for the large class of Hfq-associated small RNAs that act to
      posttranscriptionally regulate bacterial mRNAs. The function of SgrS is well
      characterized in nonpathogenic Escherichia coli, where it was originally shown to
      counteract glucose-phosphate stress by acting as a repressor of the ptsG mRNA,
      which encodes the major glucose transporter. We have discovered additional SgrS
      targets in Salmonella Typhimurium, a pathogen related to E. coli that recently
      acquired one-quarter of all genes by horizontal gene transfer. We show that the
      conserved short seed region of SgrS that recognizes ptsG was recruited to target
      the Salmonella-specific sopD mRNA of a secreted virulence protein. The SgrS-sopD
      interaction is exceptionally selective; we find that sopD2 mRNA, whose gene arose
      from sopD duplication during Salmonella evolution, is deaf to SgrS because of a
      nonproductive G-U pair in the potential SgrS-sopD2 RNA duplex vs. G-C in SgrS
      sopD. In other words, SgrS discriminates the two virulence factor mRNAs at the
      level of a single hydrogen bond. Our study suggests that bacterial pathogens use
      their large suites of conserved Hfq-associated regulators to integrate
      horizontally acquired genes into existing posttranscriptional networks, just as
      conserved transcription factors are recruited to tame foreign genes at the DNA
      level. The results graphically illustrate the importance of the seed regions of
      bacterial small RNAs to select new targets with high fidelity and suggest that
      target predictions must consider all or none decisions by individual seed
      nucleotides.

PMID- 22383561
TI  - Identification of a cis-acting element that localizes mRNA to synapses.
AB  - Messenger RNA (mRNA) localization and regulated translation can spatially
      restrict gene expression to each of the thousands of synaptic compartments formed
      by a single neuron. Although cis-acting RNA elements have been shown to direct
      localization of mRNAs from the soma into neuronal processes, less is known about
      signals that target transcripts specifically to synapses. In Aplysia sensory
      motor neuronal cultures, synapse formation rapidly redistributes the mRNA
      encoding the peptide neurotransmitter sensorin from neuritic shafts into
      synapses. We find that the export of sensorin mRNA from soma to neurite and the
      localization to synapse are controlled by distinct signals. The 3' UTR is
      sufficient for export into distal neurites, whereas the 5' UTR is required for
      concentration of reporter mRNA at synapses. We have identified a 66-nt element in
      the 5' UTR of sensorin that is necessary and sufficient for synaptic mRNA
      localization. Mutational and chemical probing analyses are consistent with a role
      for secondary structure in this process.

PMID- 22383562
TI  - Hyperosmolar therapy for intracranial hypertension: time to dispel antiquated
      myths.

PMID- 22383563
TI  - Interferon-lambda1 and viral wheeze in asthma: a Gothic duality?

PMID- 22383564
TI  - Embracing physical and neuropsychological dysfunction in acute lung injury
      survivors: the time has come.

PMID- 22383565
TI  - Innate immunity in lung fibrosis: a therapeutic role for surfactant protein D?

PMID- 22383566
TI  - Galectin-3: the bridge over troubled waters.

PMID- 22383567
TI  - Biological insights from clinical trials and networks.

PMID- 22383568
TI  - Asthma in pregnancy: are inhaled corticosteroids safe?

PMID- 22383569
TI  - Computed axial tomography scans, calories, and computers.

PMID- 22383570
TI  - Cholesterol crystals in pleural fluid.

PMID- 22383571
TI  - Steroids in idiopathic pulmonary fibrosis acute exacerbation: defenders or
      killers?

PMID- 22383572
TI  - New idiopathic pulmonary fibrosis guidelines: some unresolved questions.

PMID- 22383574
TI  - Chronic obstructive pulmonary disease phenotypes: current rather than future
      perspectives.

PMID- 22383575
TI  - Endobronchial metastasis from gastrinoma of the pancreas.

PMID- 22383576
TI  - Influence of body mass index on effects of a shared asthma treatment decision
      making intervention.

PMID- 22383577
TI  - Coagulation necrosis sign on endobronchial ultrasound.

PMID- 22383578
TI  - Identification of a binding motif specific to HNF4 by comparative analysis of
      multiple nuclear receptors.
AB  - Nuclear receptors (NRs) regulate gene expression by binding specific DNA
      sequences consisting of AG[G/T]TCA or AGAACA half site motifs in a variety of
      configurations. However, those motifs/configurations alone do not adequately
      explain the diversity of NR function in vivo. Here, a systematic examination of
      DNA binding specificity by protein-binding microarrays (PBMs) of three closely
      related human NRs--HNF4alpha, retinoid X receptor alpha (RXRalpha) and COUPTF2-
      reveals an HNF4-specific binding motif (H4-SBM), xxxxCAAAGTCCA, as well as a
      previously unrecognized polarity in the classical DR1 motif (AGGTCAxAGGTCA) for
      HNF4alpha, RXRalpha and COUPTF2 homodimers. ChIP-seq data indicate that the H4
      SBM is uniquely bound by HNF4alpha but not 10 other NRs in vivo, while NRs PXR,
      FXRalpha, Rev-Erbalpha appear to bind adjacent to H4-SBMs. HNF4-specific DNA
      recognition and transactivation are mediated by residues Asp69 and Arg76 in the
      DNA-binding domain; this combination of amino acids is unique to HNF4 among all
      human NRs. Expression profiling and ChIP data predict ~ 100 new human HNF4alpha
      target genes with an H4-SBM site, including several Co-enzyme A-related genes and
      genes with links to disease. These results provide important new insights into NR
      DNA binding.

PMID- 22383579
TI  - Engineering naturally occurring trans-acting non-coding RNAs to sense molecular
      signals.
AB  - Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While
      most trans-acting ncRNAs possess well-defined mechanisms that can regulate
      transcription or translation, they generally lack the ability to directly sense
      cellular signals. In this work, we describe a set of design principles for fusing
      ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate
      the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply
      these principles to ncRNA regulators that can regulate translation (IS10 ncRNA)
      and transcription (pT181 ncRNA), and demonstrate that our design strategy
      exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA
      target-recognition motif, which allows us to reconfigure these two motifs to
      engineer orthogonally acting fusion molecules that respond to different ligands
      and regulate different targets in the same cell. Finally, we show that the same
      ncRNA fused with different sensing domains results in a sensory-level NOR gate
      that integrates multiple input signals to perform genetic logic. These ligand
      sensing ncRNA regulators provide useful tools to modulate the activity of
      structurally related families of ncRNAs, and building upon the growing body of
      RNA synthetic biology, our ability to design aptamer-ncRNA fusion molecules
      offers new ways to engineer ligand-sensing regulatory circuits.

PMID- 22383580
TI  - The cellular abundance of the essential transcription termination factor TTF-I
      regulates ribosome biogenesis and is determined by MDM2 ubiquitinylation.
AB  - The ARF tumour suppressor stabilizes p53 by negatively regulating the E3
      ubiquitin ligase MDM2 to promote cell cycle arrest and cell death. However, ARF
      is also able to arrest cell proliferation by inhibiting ribosome biogenesis. In
      greater part this is achieved by targeting the transcription termination factor I
      (TTF-I) for nucleolar export, leading to an inhibition of both ribosomal RNA
      synthesis and processing. We now show that in the absence of ARF, TTF-I is
      ubiquitinylated by MDM2. MDM2 interacts directly with TTF-I and regulates its
      cellular abundance by targeting it for degradation by the proteasome. Enhanced
      TTF-I levels inhibit ribosome biogenesis by suppressing ribosomal RNA synthesis
      and processing, strongly suggesting that exact TTF-I levels are critical for
      efficient ribosome biogenesis. We further show that concomitant with its ability
      to displace TTF-I from the nucleolus, ARF inhibits MDM2 ubiquitinylation of TTF-I
      by competitively binding to a site overlapping the MDM2 interaction site. Thus,
      both the sub-nuclear localization and the abundance of TTF-I are key regulators
      of ribosome biogenesis.

PMID- 22383581
TI  - Selectivity of stop codon recognition in translation termination is modulated by
      multiple conformations of GTS loop in eRF1.
AB  - Translation termination in eukaryotes is catalyzed by two release factors eRF1
      and eRF3 in a cooperative manner. The precise mechanism of stop codon
      discrimination by eRF1 remains obscure, hindering drug development targeting
      aberrations at translation termination. By solving the solution structures of the
      wild-type N-domain of human eRF1 exhibited omnipotent specificity, i.e.
      recognition of all three stop codons, and its unipotent mutant with UGA-only
      specificity, we found the conserved GTS loop adopting alternate conformations. We
      propose that structural variability in the GTS loop may underline the switching
      between omnipotency and unipotency of eRF1, implying the direct access of the GTS
      loop to the stop codon. To explore such feasibility, we positioned N-domain in a
      pre-termination ribosomal complex using the binding interface between N-domain
      and model RNA oligonucleotides mimicking Helix 44 of 18S rRNA. NMR analysis
      revealed that those duplex RNA containing 2-nt internal loops interact
      specifically with helix alpha1 of N-domain, and displace C-domain from a non
      covalent complex of N-domain and C-domain, suggesting domain rearrangement in
      eRF1 that accompanies N-domain accommodation into the ribosomal A site.

PMID- 22383582
TI  - Raman spectroscopic detection of the T-Hg II-T base pair and the ionic
      characteristics of mercury.
AB  - Developing applications for metal-mediated base pairs (metallo-base-pair) has
      recently become a high-priority area in nucleic acid research, and
      physicochemical analyses are important for designing and fine-tuning molecular
      devices using metallo-base-pairs. In this study, we characterized the Hg(II)
      mediated T-T (T-Hg(II)-T) base pair by Raman spectroscopy, which revealed the
      unique physical and chemical properties of Hg(II). A characteristic Raman marker
      band at 1586 cm(-1) was observed and assigned to the C4=O4 stretching mode. We
      confirmed the assignment by the isotopic shift ((18)O-labeling at O4) and density
      functional theory (DFT) calculations. The unusually low wavenumber of the C4=O4
      stretching suggested that the bond order of the C4=O4 bond reduced from its
      canonical value. This reduction of the bond order can be explained if the enolate
      like structure (N3=C4-O4(-)) is involved as a resonance contributor in the
      thymine ring of the T-Hg(II)-T pair. This resonance includes the N-Hg(II)-bonded
      state (Hg(II)-N3-C4=O4) and the N-Hg(II)-dissociated state (Hg(II+) N3=C4-O4(-)),
      and the latter contributor reduced the bond order of N-Hg(II). Consequently, the
      Hg(II) nucleus in the T-Hg(II)-T pair exhibited a cationic character. Natural
      bond orbital (NBO) analysis supports the interpretations of the Raman
      experiments.

PMID- 22383583
TI  - Low-dose fluvastatin reverses the hypoxic pulmonary adventitial fibroblast
      phenotype in experimental pulmonary hypertension.
AB  - Hypoxic pulmonary hypertension is a worldwide public health problem. Statins
      attenuate hypoxic pulmonary hypertension in animal models, but the mechanism of
      action and applicability of these results to human treatment are not established.
      In hypoxic models, pulmonary artery fibroblast proliferation contributes
      substantially to pulmonary vascular remodeling. We previously showed that acute
      hypoxic pulmonary adventitial fibroblast proliferation can be selectively
      inhibited by statins and p38 mitogen-activated protein (MAP) kinase inhibitors.
      Here we used complementary chronic hypoxic and acute hypoxic coculture models to
      obtain necessary preclinical information regarding the utility of fluvastatin in
      the treatment of chronic hypoxic pulmonary hypertension. The effects of
      fluvastatin, cholesterol pathway intermediates, and related inhibitors on hypoxic
      adventitial fibroblast proliferation, p38 MAP kinase phosphorylation, and
      pulmonary artery smooth muscle cell proliferation were determined, using
      complementary chronic hypoxic rat and acute hypoxic bovine cell models.
      Fluvastatin reversed the proliferative phenotypic switch in adventitial
      fibroblasts from chronic hypoxic animals. This effect was circulation-specific,
      and implicated a Rac1-p38 MAP kinase signaling pathway. Coculture and conditioned
      media experiments also implicated this statin-sensitive signaling pathway in the
      release of pulmonary artery smooth muscle cell mitogens by hypoxic pulmonary
      adventitial fibroblasts. Treprostinil, sildenafil, and bosentan exerted no effect
      on the hypoxic fibroblast phenotype. Phenotypic changes (increased proliferation
      and mitogen release) in pulmonary artery fibroblasts during chronic hypoxia are
      dependent on a Rac1-p38 MAP kinase signaling pathway. The inhibition of these
      phenotypic changes with fluvastatin may be therapeutically relevant in high
      altitude residents and in patients with hypoxic lung disease.

PMID- 22383584
TI  - Influenza A induces the major secreted airway mucin MUC5AC in a protease-EGFR
      extracellular regulated kinase-Sp1-dependent pathway.
AB  - Mucins, the main glycoproteins present within mucus, modulate the rheologic
      properties of airways and participate in lung defense. They are thought to be
      able to trap and eliminate microorganisms from the lung. Among the mucins
      secreted in the lung, MUC5AC is the most prominent factor secreted by surface
      epithelial cells. Although much is known about the signaling pathways involved in
      the regulation of MUC5AC by host factors such as cytokines or proteases, less is
      known about the pathways triggered by microorganisms and, specifically, by
      influenza A virus (IAV). We therefore set up experiments to dissect the molecular
      mechanisms responsible for the potential modulation of MUC5AC by IAV. Using
      epithelial cells, C57/Bl6 mice, and IAV strains, we measured MUC5AC expression at
      the RNA and protein levels, specificity protein 1 (Sp1) activation, and protease
      activity. Intermediate molecular partners were confirmed using pharmacological
      inhibitors, blocking antibodies, and small interfering (si)RNAs. We showed in
      vitro and in vivo that IAV up-regulates epithelial cell-derived MUC5AC and Muc5ac
      expression in mice, both at transcriptional (through the induction of Sp1) and
      translational levels. In addition, we determined that this induction was
      dependent on a protease-epithelial growth factor receptor-extracellular regulated
      kinase-Sp1 signaling cascade, involving in particular the human airway trypsin.
      Our data point to MUC5AC as a potential modulatory mechanism by which the lung
      epithelia respond to IAV infection, and we dissect, for the first time to the
      best of our knowledge, the molecular partners involved. Future experiments using
      MUC5AC-targeted strategies should help further unravel the pathophysiological
      consequences of IAV-induced MUC5AC expression for lung homeostasis.

PMID- 22383585
TI  - A database of annotated promoters of genes associated with common respiratory and
      related diseases.
AB  - Many genes have been implicated in the pathogenesis of common respiratory and
      related diseases (RRDs), yet the underlying mechanisms are largely unknown.
      Differential gene expression patterns in diseased and healthy individuals suggest
      that RRDs affect or are affected by modified transcription regulation programs.
      It is thus crucial to characterize implicated genes in terms of transcriptional
      regulation. For this purpose, we conducted a promoter analysis of genes
      associated with 11 common RRDs including allergic rhinitis, asthma,
      bronchiectasis, bronchiolitis, bronchitis, chronic obstructive pulmonary disease,
      cystic fibrosis, emphysema, eczema, psoriasis, and urticaria, many of which are
      thought to be genetically related. The objective of the present study was to
      obtain deeper insight into the transcriptional regulation of these disease
      associated genes by annotating their promoter regions with transcription factors
      (TFs) and TF binding sites (TFBSs). We discovered many TFs that are significantly
      enriched in the target disease groups including associations that have been
      documented in the literature. We also identified a number of putative TFs/TFBSs
      that appear to be novel. The results of our analysis are provided in an online
      database that is freely accessible to researchers at
      http://www.respiratorygenomics.com. Promoter-associated TFBS information and
      related genomic features, such as histone modification sites, microsatellites,
      CpG islands, and SNPs, are graphically summarized in the database. Users can
      compare and contrast underlying mechanisms of specific RRDs relative to candidate
      genes, TFs, gene ontology terms, micro-RNAs, and biological pathways for the
      conduct of metaanalyses. This database represents a novel, useful resource for
      RRD researchers.

PMID- 22383586
TI  - Annual incidence of occupational diseases in economic sectors in The Netherlands.
AB  - OBJECTIVE: To report the annual incidence of occupational diseases (ODs) in
      economic sectors in The Netherlands. METHODS: In a 5-year prospective cohort
      study (2009-2013), occupational physicians were asked to participate in a
      sentinel surveillance system for OD notification. The inclusion criteria for
      participation were (1) covering a population of employees, (2) reporting the
      economic sectors and the size of their employee population and (3) willingness to
      report all diagnosed ODs. In this study, an OD was defined as a disease with a
      specific clinical diagnosis that was predominantly caused by work-related
      factors. The economic sectors (n=21) were defined according the NACE
      (Nomenclature des Activites Economiques dans la Communaute Europeenne)
      classification. RESULTS: In a total working population of 514,590 employees, 1782
      ODs were reported over 12 months in 2009. The estimated annual incidence for any
      OD was 346 (95% CI 330 to 362) per 100,000 worker-years. Of all the ODs, mental
      diseases were reported most frequently (41%), followed by musculoskeletal (39%),
      hearing (11%), infectious (4%), skin (3%), neurological (2%) and respiratory (2%)
      diseases. The four economic sectors with the highest annual incidences per
      100,000 workers were construction (1127; 95% CI 1002 to 1253), mining and
      quarrying (888; 95% CI 110 to 1667), water and waste processing (832; 95% CI 518
      to 1146) and transport and storage (608; 95% CI 526 to 690). CONCLUSION: ODs are
      reported in all economic sectors in The Netherlands. Up to 91% of all ODs are
      mental, musculoskeletal and hearing diseases. Efforts to increase the effective
      assessment of ODs and compliance in reporting activities enhance the usability of
      incidence figures for the government, employers and workers.

PMID- 22383587
TI  - Association between long-term exposure to traffic particles and blood pressure in
      the Veterans Administration Normative Aging Study.
AB  - OBJECTIVES: Particulate air pollution is associated with cardiovascular events,
      but the mechanisms are not fully understood. The main objective was to assess the
      relationship between long-term exposure to traffic-related air pollution and
      blood pressure (BP). METHODS: The authors used longitudinal data from 853 elderly
      men participating in the Veterans Administration Normative Aging Study, followed
      during 1996-2008. Long-term average exposures to traffic particles were created
      from daily predictions of black carbon (BC) exposure at the geocoded address of
      each subject, using a validated spatiotemporal model based on ambient monitoring
      at 82 Boston-area locations. The authors examined the association of these
      exposures with BP using a mixed model. The authors included the following
      covariates: age, body mass index, smoking, alcohol, fasting glucose, creatinine
      clearance, use of cardiovascular medication, education, census-level poverty, day
      of week and season of clinical visit. RESULTS: The authors found significant
      positive associations between 1-year average BC exposure and both systolic and
      diastolic blood pressure. An IQR increase in 1-year average BC exposure (0.32
      MUg/m(3)) was associated with a 2.64 mm Hg increase in systolic blood pressure
      (95% CI 1.47 to 3.80) and a 2.41 mm Hg increase in diastolic blood pressure (95%
      CI 1.77 to 3.05). CONCLUSIONS: Long-term exposure to traffic particles is
      associated with increased BP, which may explain part of the association with
      myocardial infarctions and cardiovascular deaths reported in cohort studies.

PMID- 22383588
TI  - Work-related asthma in France: recent trends for the period 2001-2009.
AB  - OBJECTIVE: Knowledge on the time-course (trends) of work-related asthma (WRA)
      remains sparse. The aim of this study was to describe WRA trends in terms of
      industrial activities and the main causal agents in France over the period 2001
      2009. METHOD: Data were collected from the French national network of
      occupational health surveillance and prevention (Reseau National de Vigilance et
      de Prevention des Pathologies Professionnelles (RNV3P)). Several statistical
      models (non-parametric test, zero-inflated negative binomial, logistic regression
      and time-series models) were used and compared with assess trends. RESULTS: Over
      the study period, 2914 WRA cases were included in the network. A significant
      decrease was observed overall and for some agents such as isocyanates (p =
      0.007), aldehydes (p = 0.01) and latex (p = 0.01). Conversely, a significant
      increase was observed for cases related to exposure to quaternary ammonium
      compounds (p = 0.003). The health and social sector demonstrated both a growing
      number of cases related to the use of quaternary ammonium compounds and a
      decrease of cases related to aldehyde and latex exposure. CONCLUSIONS: WRA
      declined in France over the study period. The only significant increase concerned
      WRA related to exposure to quaternary ammonium compounds. Zero-inflated negative
      binomial and logistic regression models appear to describe adequately these data.

PMID- 22383589
TI  - Associations between radiographic findings and spirometry in a community exposed
      to Libby amphibole.
AB  - BACKGROUND: Among asbestos-exposed individuals, abnormal spirometry is usually
      associated with parenchymal abnormalities or diffuse pleural thickening.
      Localised pleural thickening (LPT), the most common abnormality associated with
      asbestos exposure, is typically thought to be a marker of exposure with little
      clinical consequence. Our objective was to determine if abnormal spirometry is
      associated with LPT independent of other abnormalities, using data from community
      based screening conducted in Libby, Montana. METHODS: Subjects were a subset of
      screening participants comprising persons with interpretable spirometry and chest
      radiograph results (n=6475). Chest radiographs were independently evaluated by
      two or three B readers, and participants were classified by mutually exclusive
      categories of spirometry outcome: normal, restriction, obstruction or mixed
      defect. RESULTS: Restrictive spirometry was strongly associated with parenchymal
      abnormalities (OR 2.9; 95% CI 1.4 to 6.0) and diffuse pleural thickening (OR 4.1;
      95% CI 2.1 to 7.8). Controlling for the presence of these abnormalities as well
      as age, smoking status and other covariates, restrictive spirometry was also
      associated with LPT (OR 1.4; 95% CI 1.1 to 1.8). The risk of restrictive
      spirometric findings correlated with the severity of LPT. CONCLUSIONS: In this
      large community-based screening cohort, restrictive spirometry is significantly
      associated with LPT, indicating that this abnormality may result in lung function
      impairment. Physicians treating patients exposed to Libby amphibole should be
      aware that LPT may have functional consequences.

PMID- 22383590
TI  - Authors' response.

PMID- 22383591
TI  - The application of an occupational health guideline reduces sedentary behaviour
      and increases fruit intake at work: results from an RCT.
AB  - OBJECTIVE: To evaluate the effectiveness of a draft occupational health practice
      guideline aimed at preventing weight gain on employees' physical activity,
      sedentary behaviour and dietary behaviour and on body weight-related outcomes.
      METHODS: A randomised controlled trial was performed comparing guideline-based
      care to usual care among 16 occupational physicians and 523 employees in the
      Netherlands between 2009 and 2011. Occupational physicians in the intervention
      group followed the draft guideline by providing advice to employers on how to
      assess and intervene on the obesogenic work environment and conducted five face
      to-face behavioural change counselling sessions with employees to improve their
      lifestyle. Data of employees were collected by questionnaire and physical
      measurements at baseline and 6-months follow-up. Linear and logistic regression
      analyses were performed to determine effects. RESULTS: The intervention showed
      significant effects on sedentary behaviour at work (beta -28 min/day, 95% CI -2
      to -54) and on fruit intake (beta 2.1 pieces/week; 95% CI 0.6 to 3.6). No
      significant intervention effects were found for physical activity, sedentary
      behaviour in leisure time or during weekend days, snack intake and body weight
      related outcomes. CONCLUSION: Guideline-based care resulted in a more favourable
      sedentary behaviour at work and increased fruit intake but did not improve
      employees' physical activity, snack intake or body weight-related outcomes. Trial
      registration number ISRCTN/73545254 and NTR/1190.

PMID- 22383592
TI  - Risk estimate of ischaemic heart disease in workers exposed to beryllium.

PMID- 22383594
TI  - Philanthropy and dental education: "it is not necessary to change; survival is
      not mandatory".

PMID- 22383595
TI  - Social media in dental education: a call for research and action.
AB  - Social media are part of the fabric of today's world, from which health care is
      not excluded. Based on its distribution capacity, a single individual can cause
      an amount of damage to an institution that only a few decades ago required access
      to a mainstream news media outlet. Despite the obvious parallels in professional
      standards in the medical and dental communities, the scholarly activity and
      resulting collegial discourse observed among medical professionals remain
      unmatched in the dental education literature. As a result, a rigorous research
      agenda on the topic is indicated. Once these results are evaluated and thoroughly
      vetted, actions should be tailored to address the needs, minimize the threats,
      and maximize the opportunities that have been already noted by the medical
      profession. Regardless of input, albeit internal or external, a cadre of
      individuals who are willing to develop philosophy, policy, and procedure related
      to the use of social media policies in dental education can then be identified to
      evaluate the issues unique to the institution and perhaps the profession.

PMID- 22383596
TI  - Why intravenous moderate sedation should be taught in graduate endodontic
      programs.
AB  - The purpose of this opinion article is to present reasons why intravenous
      moderate sedation should be taught in graduate endodontic programs. Access to
      oral health care is an area of much interest and concern, but some patients are
      unable to get endodontic care because they have special needs. Special needs can
      refer to patients who fear dentistry itself and other aspects of dental
      treatment. A variety of phobias and medical, developmental, and physical
      conditions can make it difficult for some patients to tolerate the endodontic
      care they need and want. Moderate sedation can help many of these patients.
      Endodontists in general are not trained to provide intravenous moderate sedation.
      By incorporating intravenous moderate sedation into endodontic practice, many of
      these patients can be treated. The first step in achieving this goal is to add
      intravenous moderate sedation training to graduate endodontic programs. The long
      term effect will be to make specialty endodontic care available to more people.

PMID- 22383597
TI  - Learning curves: what do dental students learn from repeated practice of clinical
      procedures?
AB  - It is generally accepted that repetition of procedures is necessary to develop
      clinical skill in dentistry. Although there is a rich empirical research
      tradition in medicine establishing competency levels for new procedures,
      investigations of the shape of learning curves for clinical techniques are rare
      in dental education. Data were reviewed from three classes (n=465) of students at
      the University of the Pacific Arthur A. Dugoni School of Dentistry in seventeen
      clinical skills in five departments for which test case (independent performance)
      data were available. It was hypothesized that a learning curve would be observed
      with gradually rising scores as a function of amount of repeated test case work
      and general practice experience. Other factors, such as faculty ratings and
      clinical GPA, could be expected to modify this curve. No evidence was found that
      test case performance was affected by number of previous test cases, number of
      practice (ungraded) procedures previously completed, faculty ratings of technical
      skill in the discipline by quarter, faculty ratings of patient management and of
      clinical judgment competencies, overall clinical GPA, and performance on initial
      licensure examinations. The absence of a pattern showing that amount of prior
      experience improves clinical performance raises questions about the practice of
      setting "requirements" for graduation and challenges dental educators to better
      explain the presumed relationship between practice and performance and the
      validity of clinical evaluation of performance based exclusively on the objective
      technical quality of work samples. The literature on learning curves and on
      competency-based education offer alternative insights into what students are
      actually learning but schools are failing to measure in the clinical experience.

PMID- 22383598
TI  - Advancing the educational training of dental educators: review of a model
      program.
AB  - Very few dental educators have formal pedagogical training, and the availability
      of degree-granting programs for dental educators is very limited. A joint D.D.S.
      M.A. program for predoctoral students and a Ph.D. program for faculty members
      have been established at Columbia University's College of Dental Medicine in
      conjunction with the Graduate School of Education, Teachers College. Six students
      have completed the joint degree program, five are currently enrolled, and an
      additional three have taken courses at Teachers College without pursuing a
      degree. One faculty member has completed the Ph.D. program, and one is enrolled.
      This article describes the details of both programs and discusses preliminary
      outcomes. The model described here may serve as an example for other dental
      schools that may choose to implement degree programs in education for dental
      educators.

PMID- 22383599
TI  - A model for cultivating dental hygiene faculty development within a community of
      practice.
AB  - There is a need to explore approaches in faculty development that will foster
      change in actual teaching practices. The literature suggests that there should be
      more deliberate use of theory in faculty development research. This study
      addressed this gap in the literature by exploring social learning theory in the
      context of communities of practice and applying this theory to a dental hygiene
      faculty development program. The purpose of the study was to determine if
      participation in a community of practice helped dental hygiene clinical
      instructors implement new teaching strategies by providing ongoing support for
      their learning. In addition, the study explored whether the level of
      participation in the community changed over time. A retrospective self-assessment
      questionnaire consisting of four open-ended questions was administered to a group
      of clinical dental hygiene instructors at the end of the 2010 academic year. The
      narrative data were analyzed thematically using qualitative methodology. The
      results indicated that participation in the community of practice helped clinical
      instructors make effective changes in their teaching practices by optimizing
      social learning opportunities. The responses also revealed that instructors
      became more comfortable participating in discussions as they identified with
      other members of this unique community.

PMID- 22383600
TI  - Interactive distance learning in orthodontic residency programs: problems and
      potential solutions.
AB  - Sharing resources through distance education has been proposed as one way to deal
      with a lack of full-time faculty members and maintain high-quality content in
      orthodontic residency programs. To keep distance education for orthodontic
      residents cost-effective while retaining interaction, a blended approach was
      developed that combines observation of web-based seminars with live post-seminar
      discussions. To evaluate this approach, a grant from the American Association of
      Orthodontists (AAO) opened free access during the 2009-10 academic year to twenty
      five recorded seminars in four instructional sequences to all sixty-three
      orthodontic programs in the United States and Canada. The only requirement was to
      also participate in the evaluation. Just over half (52 percent) of the U.S.
      programs chose to participate; the primary reason for participating was because
      faculty members wanted their residents to have exposure to other faculty members
      and ideas. The non-participating programs cited technical and logistical problems
      and their own ability to teach these subjects satisfactorily as reasons. Although
      participating distant faculty members and residents were generally pleased with
      the experience, problems in both educational and technical aspects were observed.
      Educationally, the biggest problem was lack of distant resident preparation and
      expectation of a lecture rather than a seminar. Technically, the logistics of
      scheduling distant seminars and uneven quality of the audio and video recordings
      were the major concerns of both residents and faculty members. Proposed solutions
      to these educational and technical problems are discussed.

PMID- 22383601
TI  - A case-based and team-based learning model in oral and maxillofacial radiology.
AB  - The purpose of this article is to describe the process of transitioning a
      traditional face-to-face oral and maxillofacial radiology (OMR) lecture course to
      a case-based, team-based learning model for students ready to enter their fourth
      and final year of dental school. Data were collected from 294 new fourth-year
      students (Classes of 2009, 2010, and 2011) who participated in the newly
      formatted OMR course. At the time the course was taken, students had completed
      one year of clinical experience in taking and evaluating radiographic images on
      patients with various clinical conditions. Each class of approximately 100
      students was divided into ten teams of ten each, and a topic on oral and
      maxillofacial lesions was assigned to each team. The teams researched their
      assigned topics, created PowerPoint presentations, and posted them on the course
      management system Blackboard site. The instructor posted on Blackboard eight to
      ten cases representing various lesions on that topic. Minimal clinical history
      was released at that point. Students reviewed the teams' PowerPoint presentations
      and the cases, answered the questions for each case, and turned in written
      assignments to be graded. The diagnoses were discussed in class. An end-of-course
      survey found that 71 percent of the students felt the case-based instruction
      helped them learn the content in a more comprehensive manner and 77 percent felt
      the in-class discussion increased their knowledge of radiographic interpretation.
      Some students said they felt uncomfortable being called on randomly during the
      class discussion. National Board Dental Examination results for the classes of
      2009 and 2010 showed slight improvement when compared to national scores. As a
      result of student feedback, the course continues to be offered in the case-based,
      team-based format.

PMID- 22383602
TI  - Early failure of Class II resin composite versus Class II amalgam restorations
      placed by dental students.
AB  - Using the information from remake request slips in a dental school's predoctoral
      clinic, we examined the short-term survival of Class II resin composite
      restorations versus Class II dental amalgam restorations. In the student clinic,
      resin composite is used in approximately 58 percent of Class II restorations
      placed, and dental amalgam is used in the remaining 42 percent. In the period
      examined, Class II resin composite restorations were ten times more likely to be
      replaced at no cost to the patient than Class II dental amalgam restorations. A
      total of eighty-four resin composite restorations and six amalgam restorations
      were replaced due to an identified failure.

PMID- 22383603
TI  - Impact of a prior medical degree on students' dental school performance in
      Innsbruck, Austria.
AB  - The purpose of this study was to identify the performance differences between two
      groups of Austrian dental students (one with a prior medical degree and one
      without a medical degree) during their dental school training and final dental
      licensure examination. A specific aim was to determine if having a medical degree
      is a predictive factor for dental students' scores on the Austrian Dental
      Admission Test (Austrian DAT), performance in the dental clinic, and scores on
      final exam. The study consisted of a retrospective analysis of 122 students
      (thirty-nine with a medical degree and eighty-three without a medical degree) who
      were enrolled in the Dental Clinic at Innsbruck Medical University, Innsbruck,
      Austria, between 2001 and 2006. Three performance categories were considered:
      Austrian DAT results, clinical performance after the first clinical year in
      dental school, and performance on the final dental licensure examination.
      Information on students' age, gender, and previous medical degree was collected
      from official records. Analyses with student's t-test and Pearson's chi-square
      test revealed that the students with a medical degree had significantly higher
      Austrian DAT total test scores, grade point averages after the first clinical
      year, and scores on the final exam. Additionally, those students had
      significantly better performance on the final exam in prosthodontics and oral and
      maxillofacial surgery. The linear regression analysis showed that a medical
      degree had an independent effect on average scores on the final exam, age, and
      Austrian DAT test scores, while gender showed no statistically significant
      effect. Overall, the study found that dental students with a prior medical degree
      had significantly higher Austrian DAT total test scores and performed
      significantly better in the first clinical year and on the final exam than those
      without a prior medical degree.

PMID- 22383604
TI  - Curriculum information models in health professions education in Australia: an
      innovative approach to efficient curriculum design, development, and maintenance.
AB  - Over the last decade, there has been a significant increase in attention to the
      overall accountability of higher education in Australia, and this is expected to
      continue. Increased accountability has led to the need for more explicitly
      documented curricula. The curricula from ten health-related disciplines developed
      over the last five years in Australia were the basis of this study. Curriculum
      information modeling is an approach that allows for the dynamic nature of
      curricula since elements and their linkages can be moved about and reconnected
      into meaningful patterns. In addition, the models give disciplines and
      institutions the ability to effectively monitor curricula and draw comparisons in
      a more unified manner. Curriculum information models are an efficient innovation
      in the design and management of curricula in higher education and particularly in
      the health care disciplines. They rest on the principles of reusable elements and
      linkages independent of content that were first used in the design, construction,
      and maintenance of buildings. The translation of this approach to the higher
      education sector provides a higher level of interoperability of resources and a
      clearer pathway for content design within a curriculum.

PMID- 22383605
TI  - Effect of a procedural video CD and study guide on the practical fixed
      prosthodontic performance of Iranian dental students.
AB  - Dental students in programs around the world typically pass preclinical courses
      before entering the clinic and working on actual patients. Since fixed
      prosthodontics is a preclinical course that requires a great deal of effort,
      students may experience a substantial amount of stress that may affect their self
      confidence and/or clinical performance. In this study, an instructional video CD
      (VCD) and study guide depicting the step-by-step procedures involved in a metal
      ceramic tooth preparation and provisional crown fabrication was prepared.
      Students at the Faculty of Dentistry, Tehran University of Medical Sciences,
      Tehran, Iran, were divided randomly into two groups. Group A students trained as
      usual with live patients, and Group B students were given a copy of the VCD and
      study guide following a lecture. The students in Group B were encouraged to read
      the study guide and watch the VCD after live demonstrations. Then, both groups
      practiced individually on mannequins. At the end of the course, the students
      completed a sixteen-item questionnaire about their stress level, self-confidence,
      and knowledge base. The results showed that the students exposed to the extra
      media performed significantly better on some practical phases, e.g., laboratory
      procedures. A moderate, insignificant correlation was detected between exposure
      to media and decreasing the students' stress and self-esteem. We concluded that
      supplementary teaching aids such as a VCD and study guide may improve the
      clinical performance of dental students to some extent, but the live
      demonstration is still preferred by students.

PMID- 22383606
TI  - Teaching dental students how to deliver bad news: S-P-I-K-E-S model.
AB  - Delivering bad news has traditionally been associated with life-threatening
      illness, the imminence of death, or communicating about the death of a loved one
      to a family member. The delivery of bad news in dentistry is rarely about life
      threatening circumstances. However, the impact of the bad news such as the loss
      of an anterior tooth can be devastating for the patient. This article outlines
      the S-P-I-K-E-S protocol and discusses the teaching aims and methodology in
      applying the model in an undergraduate dental program in Ireland.

PMID- 22383607
TI  - Indian dental students' preferences regarding lecture courses.
AB  - Teaching and learning activities in the dental clinic or hospital are a
      challenging area for students as well as teachers. With various teaching
      methodologies being used in dental schools around the world, gaining greater
      understanding of students' attitudes toward these methodologies would be useful
      for dental educators. The objective of this study was to explore the preferences
      of dental students in India about various aspects of lecture courses. A
      structured survey consisting of ten closed-ended questions was developed, and
      2,680 undergraduate students from forty-three dental schools in India were
      approached via e-mail with a follow-up postal mailing. Of these, 1,980 students
      responded, for a response rate of 73.8 percent. Most of the students reported
      preferring lectures with the aid of PowerPoint and chalkboard. They preferred
      morning lectures from 8 am to 10 am for a maximum of thirty to forty minutes for
      each lecture, and they preferred to receive information about the lecture topic
      in advance. The students said that delivery of clinical demonstrations was
      beneficial after the lectures, and they preferred learning-based rather than exam
      oriented education. The respondents also said that attendance should be made
      compulsory and that numerical marking of examinations should not be replaced by a
      grading system.

PMID- 22383608
TI  - Quality considerations in dental education in India.
AB  - Undergraduate dental education programs have grown tremendously in India over the
      last five to six decades, mainly in the private sector, putting significant
      pressure on resources including faculty. This has raised concerns about the
      quality of dental education in the country. This article examines the concept of
      quality as applicable to higher education. It provides a roadmap for application
      of quality concepts, including steps for improving the effectiveness of teaching
      and applying Total Quality Management to dental education. It also makes
      suggestions for college-level and structural-level changes to meet the
      requirement of improved quality, which includes the addition of dental education
      as a subject in postgraduate dental programs.

PMID- 22383609
TI  - When biomedical animal research makes "sense".

PMID- 22383610
TI  - Catching education up with technology: preparing the public to make informed
      choices about personal genetics.

PMID- 22383611
TI  - The role of the lecturer as tutor: doing what effective tutors do in a large
      lecture class.

PMID- 22383612
TI  - Evolution education across the life sciences: making biology education make
      sense.

PMID- 22383613
TI  - Writing-to-learn in undergraduate science education: a community-based,
      conceptually driven approach.
AB  - Despite substantial evidence that writing can be an effective tool to promote
      student learning and engagement, writing-to-learn (WTL) practices are still not
      widely implemented in science, technology, engineering, and mathematics (STEM)
      disciplines, particularly at research universities. Two major deterrents to
      progress are the lack of a community of science faculty committed to undertaking
      and applying the necessary pedagogical research, and the absence of a conceptual
      framework to systematically guide study designs and integrate findings. To
      address these issues, we undertook an initiative, supported by the National
      Science Foundation and sponsored by the Reinvention Center, to build a community
      of WTL/STEM educators who would undertake a heuristic review of the literature
      and formulate a conceptual framework. In addition to generating a searchable
      database of empirically validated and promising WTL practices, our work lays the
      foundation for multi-university empirical studies of the effectiveness of WTL
      practices in advancing student learning and engagement.

PMID- 22383614
TI  - Using science songs to enhance learning: an interdisciplinary approach.
AB  - Music is recognized as an effective mode of teaching young children but is rarely
      used in university-level science courses. This article reviews the somewhat
      limited evidence on whether and how content-rich music might affect college
      students' understanding of science and offers practical suggestions for
      incorporating music into courses. Aside from aiding memorization, songs may
      potentially improve learning by helping students feel relaxed and welcome in
      stressful settings, engaging students through multiple modes (verbal vs.
      nonverbal) and modalities (auditory vs. visual vs. kinesthetic) simultaneously,
      challenging students to integrate and "own" the material through the medium of
      song lyrics, and increasing students' time on task outside of class through
      enjoyable listening or songwriting assignments. Students may produce content-rich
      songs of good quality if given sufficient assistance and encouragement by
      instructors and peers. The challenges ahead include 1) defining the circumstances
      in which music is most likely to promote learning and 2) developing rubrics for
      evaluating the quality of songs.

PMID- 22383615
TI  - Molecular thermodynamics for cell biology as taught with boxes.
AB  - Thermodynamic principles are basic to an understanding of the complex fluxes of
      energy and information required to keep cells alive. These microscopic machines
      are nonequilibrium systems at the micron scale that are maintained in pseudo
      steady-state conditions by very sophisticated processes. Therefore, several
      nonstandard concepts need to be taught to rationalize why these very ordered
      systems proliferate actively all over our planet in seeming contradiction to the
      second law of thermodynamics. We propose a model consisting of boxes with
      different shapes that contain small balls that are in constant motion due to a
      stream of air blowing from below. This is a simple macroscopic system that can be
      easily visualized by students and that can be understood as mimicking the
      behavior of a set of molecules exchanging energy. With such boxes, the basic
      concepts of entropy, enthalpy, and free energy can be taught while reinforcing a
      molecular understanding of the concepts and stressing the stochastic nature of
      the thermodynamic laws. In addition, time-related concepts, such as reaction
      rates and activation energy, can be readily visualized. Moreover, the boxes
      provide an intuitive way to introduce the role in cellular organization of
      "information" and Maxwell's demons operating under nonequilibrium conditions.

PMID- 22383616
TI  - The utility of writing assignments in undergraduate bioscience.
AB  - We tested the hypothesis that engagement in a few, brief writing assignments in a
      nonmajors science course can improve student ability to convey critical thought
      about science. A sample of three papers written by students (n = 30) was coded
      for presence and accuracy of elements related to scientific writing. Scores for
      different aspects of scientific writing were significantly correlated, suggesting
      that students recognized relationships between components of scientific thought.
      We found that students' ability to write about science topics and state
      conclusions based on data improved over the course of three writing assignments,
      while the abilities to state a hypothesis and draw clear connections between
      human activities and environmental impacts did not improve. Three writing
      assignments generated significant change in student ability to write
      scientifically, although our results suggest that three is an insufficient number
      to generate complete development of scientific writing skills.

PMID- 22383617
TI  - Exploring undergraduates' understanding of photosynthesis using diagnostic
      question clusters.
AB  - We present a diagnostic question cluster (DQC) that assesses undergraduates'
      thinking about photosynthesis. This assessment tool is not designed to identify
      individual misconceptions. Rather, it is focused on students' abilities to apply
      basic concepts about photosynthesis by reasoning with a coordinated set of
      practices based on a few scientific principles: conservation of matter,
      conservation of energy, and the hierarchical nature of biological systems. Data
      on students' responses to the cluster items and uses of some of the questions in
      multiple-choice, multiple-true/false, and essay formats are compared. A cross
      over study indicates that the multiple-true/false format shows promise as a
      machine-gradable format that identifies students who have a mixture of accurate
      and inaccurate ideas. In addition, interviews with students about their choices
      on three multiple-choice questions reveal the fragility of students'
      understanding. Collectively, the data show that many undergraduates lack both a
      basic understanding of the role of photosynthesis in plant metabolism and the
      ability to reason with scientific principles when learning new content.
      Implications for instruction are discussed.

PMID- 22383618
TI  - Using targeted active-learning exercises and diagnostic question clusters to
      improve students' understanding of carbon cycling in ecosystems.
AB  - In this study, we used targeted active-learning activities to help students
      improve their ways of reasoning about carbon flow in ecosystems. The results of a
      validated ecology conceptual inventory (diagnostic question clusters [DQCs])
      provided us with information about students' understanding of and reasoning about
      transformation of inorganic and organic carbon-containing compounds in biological
      systems. These results helped us identify specific active-learning exercises that
      would be responsive to students' existing knowledge. The effects of the active
      learning interventions were then examined through analysis of students' pre- and
      postinstruction responses on the DQCs. The biology and non-biology majors
      participating in this study attended a range of institutions and the instructors
      varied in their use of active learning; one lecture-only comparison class was
      included. Changes in pre- to postinstruction scores on the DQCs showed that an
      instructor's teaching method had a highly significant effect on student reasoning
      following course instruction, especially for questions pertaining to cellular
      level, carbon-transforming processes. We conclude that using targeted in-class
      activities had a beneficial effect on student learning regardless of major or
      class size, and argue that using diagnostic questions to identify effective
      learning activities is a valuable strategy for promoting learning, as gains from
      lecture-only classes were minimal.

PMID- 22383619
TI  - Using student learning and development outcomes to evaluate a first-year
      undergraduate group video project.
AB  - Students in an interdisciplinary undergraduate introductory course were required
      to complete a group video project focused on nutrition and healthy eating. A
      mixed-methods approach to data collection involved observing and rating video
      footage of group work sessions and individual and focus group interviews. These
      data were analyzed and used to evaluate the effectiveness of the assignment in
      light of two student learning outcomes and two student development outcomes at
      the University of Minnesota. Positive results support the continued inclusion of
      the project within the course, and recommend the assignment to other programs as
      a viable means of promoting both content learning and affective behavioral
      objectives.

PMID- 22383620
TI  - Using comparative genomics for inquiry-based learning to dissect virulence of
      Escherichia coli O157:H7 and Yersinia pestis.
AB  - Genomics and bioinformatics are topics of increasing interest in undergraduate
      biological science curricula. Many existing exercises focus on gene annotation
      and analysis of a single genome. In this paper, we present two educational
      modules designed to enable students to learn and apply fundamental concepts in
      comparative genomics using examples related to bacterial pathogenesis. Students
      first examine alignments of genomes of Escherichia coli O157:H7 strains isolated
      from three food-poisoning outbreaks using the multiple-genome alignment tool
      Mauve. Students investigate conservation of virulence factors using the Mauve
      viewer and by browsing annotations available at the A Systematic Annotation
      Package for Community Analysis of Genomes database. In the second module,
      students use an alignment of five Yersinia pestis genomes to analyze single
      nucleotide polymorphisms of three genes to classify strains into biovar groups.
      Students are then given sequences of bacterial DNA amplified from the teeth of
      corpses from the first and second pandemics of the bubonic plague and asked to
      classify these new samples. Learning-assessment results reveal student
      improvement in self-efficacy and content knowledge, as well as students' ability
      to use BLAST to identify genomic islands and conduct analyses of virulence
      factors from E. coli O157:H7 or Y. pestis. Each of these educational modules
      offers educators new ready-to-implement resources for integrating comparative
      genomic topics into their curricula.

PMID- 22383621
TI  - Teaching the biological consequences of alcohol abuse through an online game:
      impacts among secondary students.
AB  - A multimedia game was designed to serve as a dual-purpose intervention that
      aligned with National Science Content Standards, while also conveying knowledge
      about the consequences of alcohol consumption for a secondary school audience. A
      tertiary goal was to positively impact adolescents' attitudes toward science
      through career role-play experiences within the game. In a pretest/delayed
      posttest design, middle and high school students, both male and female,
      demonstrated significant gains on measures of content knowledge and attitudes
      toward science. The best predictors of these outcomes were the players' ratings
      of the game's usability and satisfaction with the game. The outcomes suggest that
      game interventions can successfully teach standards-based science content, target
      age-appropriate health messages, and impact students' attitudes toward science.

PMID- 22383622
TI  - Visualizing protein interactions and dynamics: evolving a visual language for
      molecular animation.
AB  - Undergraduate biology education provides students with a number of learning
      challenges. Subject areas that are particularly difficult to understand include
      protein conformational change and stability, diffusion and random molecular
      motion, and molecular crowding. In this study, we examined the relative
      effectiveness of three-dimensional visualization techniques for learning about
      protein conformation and molecular motion in association with a ligand-receptor
      binding event. Increasingly complex versions of the same binding event were
      depicted in each of four animated treatments. Students (n = 131) were recruited
      from the undergraduate biology program at University of Toronto, Mississauga.
      Visualization media were developed in the Center for Molecular and Cellular
      Dynamics at Harvard Medical School. Stem cell factor ligand and cKit receptor
      tyrosine kinase were used as a classical example of a ligand-induced receptor
      dimerization and activation event. Each group completed a pretest, viewed one of
      four variants of the animation, and completed a posttest and, at 2 wk following
      the assessment, a delayed posttest. Overall, the most complex animation was the
      most effective at fostering students' understanding of the events depicted. These
      results suggest that, in select learning contexts, increasingly complex
      representations may be more desirable for conveying the dynamic nature of cell
      binding events.

PMID- 22383625
TI  - RNA processing bodies, peroxisomes, Golgi bodies, mitochondria, and endoplasmic
      reticulum tubule junctions frequently pause at cortical microtubules.
AB  - Organelle motility, essential for cellular function, is driven by the
      cytoskeleton. In plants, actin filaments sustain the long-distance transport of
      many types of organelles, and microtubules typically fine-tune the motile
      behavior. In shoot epidermal cells of Arabidopsis thaliana seedlings, we show
      here that a type of RNA granule, the RNA processing body (P-body), is transported
      by actin filaments and pauses at cortical microtubules. Interestingly, removal of
      microtubules does not change the frequency of P-body pausing. Similarly, we show
      that Golgi bodies, peroxisomes, and mitochondria all pause at microtubules, and
      again the frequency of pauses is not appreciably changed after microtubules are
      depolymerized. To understand the basis for pausing, we examined the endoplasmic
      reticulum (ER), whose overall architecture depends on actin filaments. By the
      dual observation of ER and microtubules, we find that stable junctions of tubular
      ER occur mainly at microtubules. Removal of microtubules reduces the number of
      stable ER tubule junctions, but those remaining are maintained without
      microtubules. The results indicate that pausing on microtubules is a common
      attribute of motile organelles but that microtubules are not required for
      pausing. We suggest that pausing on microtubules facilitates interactions between
      the ER and otherwise translocating organelles in the cell cortex.

PMID- 22383626
TI  - Protein-protein interactions in plants.
AB  - The study of protein-protein interactions (PPIs) is essential to uncover unknown
      functions of proteins at the molecular level and to gain insight into complex
      cellular networks. Affinity purification and mass spectrometry (AP-MS), yeast two
      hybrid, imaging approaches and numerous diverse databases have been developed as
      strategies to analyze PPIs. The past decade has seen an increase in the number of
      identified proteins with the development of MS and large-scale proteome analyses.
      Consequently, the false-positive protein identification rate has also increased.
      Therefore, the general consensus is to confirm PPI data using one or more
      independent approaches for an accurate evaluation. Furthermore, identifying minor
      PPIs is fundamental for understanding the functions of transient interactions and
      low-abundance proteins. Besides establishing PPI methodologies, we are now seeing
      the development of new methods and/or improvements in existing methods, which
      involve identifying minor proteins by MS, multidimensional protein identification
      technology or OFFGEL electrophoresis analyses, one-shot analysis with a long
      column or filter-aided sample preparation methods. These advanced techniques
      should allow thousands of proteins to be identified, whereas in-depth proteomic
      methods should permit the identification of transient binding or PPIs with weak
      affinity. Here, the current status of PPI analysis is reviewed and some advanced
      techniques are discussed briefly along with future challenges for plant
      proteomics.

PMID- 22383627
TI  - Proteomic analysis of embryonic proteins synthesized from long-lived mRNAs during
      germination of rice seeds.
AB  - Dry seeds contain translatable, long-lived mRNAs that are stored during seed
      maturation. Early studies using transcriptional inhibitors supported the view
      that protein synthesis during the initial phase of germination occurs on long
      lived mRNA templates. Rice seeds were treated with the transcriptional inhibitor
      actinomycin D (Act D), and the embryonic proteins translated from long-lived
      mRNAs during germination were identified using a proteomic analysis. De novo
      transcription was not required for germination of rice seeds, since >80% of seeds
      germinated when transcription was prevented by treatment with Act D. In contrast,
      germination was completely inhibited in the presence of cycloheximide, an
      inhibitor of translation. Thus, de novo protein synthesis is necessary for
      germination of rice seeds. The proteomic analysis revealed that 20 proteins are
      up-regulated during germination, even after Act D treatment. Many of the up
      regulated proteins are involved in carbohydrate metabolism and cytoskeleton
      formation. These results indicate that some of the germination-specific proteins
      involved in energy production and maintenance of cell structure in rice seeds are
      synthesized from long-lived mRNAs. The timing of translation of eight up
      regulated proteins was clearly later than that of the other up-regulated proteins
      under conditions in which transcription was inhibited by Act D, suggesting that
      translation of long-lived mRNAs in rice seeds is regulated according to the
      germination phase.

PMID- 22383628
TI  - Arabidopsis zinc finger proteins AtC3H49/AtTZF3 and AtC3H20/AtTZF2 are involved
      in ABA and JA responses.
AB  - There are 68 CCCH zinc finger protein genes in the Arabidopsis genome. However,
      only a few of them have been characerized functionally. In this paper, we report
      the function of two Arabidopsis CCCH zinc finger proteins AtC3H49/AtTZF3 and
      AtC3H20/AtTZF2. To investigate their functions, we examined their expression
      patterns and analyzed their overexpression and knockout(KO)/RNA interference
      (RNAi) phenotypes. Both AtC3H49/AtTZF3 and AtC3H20/AtTZF2 genes were expressed in
      various vegetative tissues and in flowers, and their encoded proteins were
      localized in the cytoplasm. Overexpression of AtC3H49/AtTZF3 or AtC3H20/AtTZF2
      conferred ABA hypersensitivity, reduced transpiration and enhanced drought
      tolerance. Their overexpression also altered the plant growth pattern. The
      transgenic plants grew slowly during the early stage of growth, but their growth
      rates were accelerated at later stages, and mature plants were larger than the
      wild-type plants. Moreover, the transgenic plants displayed delayed senescence
      and enhanced longevity. Subsequent experiments showed that jasmonic acid (JA)
      induced senescence was also delayed. Microarray and quantitative reverse
      transcription-PCR analyses indicated that the expression of a number of genes
      involved in JA, ABA and biotic/abiotic stress responses was altered in the
      transgenic lines. Recombinant AtC3H49/AtTZF3 and AtC3H20/AtTZF2 proteins
      displayed RNase activity in vitro, suggesting that they may be involved in mRNA
      turnover process. The knockout/RNAi lines of AtC3H49/AtTZF3 and AtC3H20/AtTZF2
      exhibited weak phenotypes, presumably because of their functional redundancy.

PMID- 22383629
TI  - Goalpha expression in the vomeronasal organ and olfactory bulb of the tammar
      wallaby.
AB  - The vomeronasal organ (VNO) detects pheromones via 2 large families of receptors:
      vomeronasal receptor 1, associated with the protein Gialpha2, and vomeronasal
      receptor 2, associated with Goalpha. We investigated the distribution of Goalpha
      in the developing and adult VNO and adult olfactory bulb of a marsupial, the
      tammar wallaby. Some cells expressed Goalpha as early as day 5 postpartum, but by
      day 30, Goalpha expressing cells were distributed throughout the receptor
      epithelium of the VNO. In the adult tammar, Goalpha appeared to be expressed in
      sensory neurons whose nuclei were mostly basally located in the vomeronasal
      receptor epithelium. Goalpha expressing vomeronasal receptor cells led to all
      areas of the accessory olfactory bulb (AOB). The lack of regionally restricted
      projection of the vomeronasal receptor cell type 2 in the tammar was similar to
      the uniform type, with the crucial difference that the uniform type only shows
      expression of Gialpha2 and no expression of Goalpha. The observed Goalpha
      staining pattern suggests that the tammar may have a third accessory olfactory
      type that could be intermediate to the segregated and uniform types already
      described.

PMID- 22383630
TI  - Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and
      reduces inflammation in continuous ambulatory peritoneal dialysis patients--a
      randomized crossover trial.
AB  - BACKGROUND: The aim of the present study was to investigate the effect of oral
      pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and
      adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD)
      patients. METHODS: In this randomized crossover trial, 36 CAPD patients with
      serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive
      either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week
      washout, the patients were switched to the alternative regimen. The primary
      endpoint was change in serum triglycerides during the PIO regimen compared with
      no PIO. Secondary endpoints included changes in other lipid levels, homeostatic
      model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive
      protein (CRP). RESULTS: All 36 CAPD patients (age: 64 +/- 11 years; 33% men;
      27.8% with diabetes mellitus) completed the study. Comparing patients after PIO
      and no PIO therapy, we found no significant differences in mean serum
      triglycerides (3.83 +/- 1.49 mmol/L vs 3.51 +/- 1.98 mmol/L, p = 0.2). However,
      mean high-density lipoprotein (0.94 +/- 0.22 mmol/L vs 1.00 +/- 0.21 mmol/L, p =
      0.004) and median total adiponectin [10.34 MUg/mL (range: 2.59 - 34.48 MUg/mL) vs
      30.44 MUg/mL (3.47 - 93.41 MUg/mL), p < 0.001] increased significantly. Median
      HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting
      blood glucose (7.31 +/- 2.57 mmol/L vs 6.60 +/- 2.45 mmol/L, p = 0.01), median
      CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and
      mean resistin (32.70 +/- 17.17 ng/mL vs 28.79 +/- 11.83 ng/mL, p = 0.02) all
      declined. The PIO was well tolerated, with only one adverse event: lower
      extremity edema in a patient with low residual renal function. CONCLUSIONS: Blood
      triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD
      patients, but parameters of dysmetabolism were markedly improved, including
      insulin resistance, inflammation, and adipokine balance, suggesting that PIO
      could be of value for this high-risk patient group. Larger, more definitive
      studies are needed to confirm these findings.

PMID- 22383631
TI  - Two-in-one protocol: simultaneous small-pore and ultrasmall-pore peritoneal
      transport quantification.
AB  - BACKGROUND: Reduced free water transport (FWT) through ultrasmall pores
      contributes to net ultrafiltration failure (UFF) and should be seen as a sign of
      more severe functional deterioration of the peritoneal membrane. The modified
      peritoneal equilibration test (PET), measuring the dip in dialysate Na
      concentration, estimates only FWT. Our aim was to simultaneously quantify small
      solute transport, FWT, and small-pore ultrafiltration (SPUF) during a single PET
      procedure. METHODS: We performed a 4-hour, 3.86% glucose PET, with additional
      measurement of ultrafiltration (UF) at 60 minutes, in 70 peritoneal dialysis
      patients (mean age: 50 +/- 16 years; 61% women; PD vintage: 26 +/- 23 months). We
      calculated the dialysate-to-plasma ratios (D/P) of creatinine and Na at 0 and 60
      minutes, and the Na dip (Dip(D/PNa60')), the delta dialysate Na 0-60 (DeltaDNa(0
      60)), FWT, and SPUF. RESULTS: Sodium sieving (as measured by DeltaDNa(0-60))
      correlated strongly with the corrected Dip(D/PNa60') (r = 0.85, p < 0.0001) and
      the corrected FWT (r = 0.41, p = 0.005). Total UF showed better correlation with
      FWT than with indirect measurements of Na sieving (r = 0.46, p < 0.0001 for FWT;
      r = 0.360, p < 0.0001 for Dip(D/PNa60')). Corrected FWT fraction was 0.45 +/-
      0.16. A negative correlation was found between time on PD and both total UF and
      FWT (r = -0.253, p = 0.035 and r = -0.272, p = 0.023 respectively). The 11
      patients (15.7%) diagnosed with UFF had lower FWT (89 mL vs 164 mL, p < 0.05) and
      higher D/P creatinine (0.75 vs 0.70, p < 0.05) than did the group with normal UF.
      The SPUF correlated positively with FWT in the normal UF group, but negatively in
      UFF patients (r = -0.709, p = 0.015). Among UFF patients on PD for a longer
      period, 44.4% had a FWT percentage below 45%. CONCLUSIONS: Measurement of FWT and
      SPUF is feasible by simultaneous quantification during a modified 3.86% glucose
      PET, and FWT is a decisive parameter for detecting causes of UFF in addition to
      increased effective capillary surface.

PMID- 22383632
TI  - A new neutral-pH low-GDP peritoneal dialysis fluid.
AB  - BACKGROUND: Conventional peritoneal dialysis fluids (PDFs) consist of ready-to
      use solutions with an acidic pH. Sterilization of these fluids is known to
      generate high levels of glucose degradation products (GDPs). Although several
      neutral-pH, low-GDP PD solutions have been developed, none are commercially
      available in the United States. We analyzed pH and GDPs in Delflex Neutral pH
      (Fresenius Medical Care North America, Waltham, MA, USA), the first neutral-pH
      PDF to be approved by the US Food and Drug Administration. METHODS: We evaluated
      whether patients (n = 26; age range: 18 - 78 years) could properly mix the
      Delflex Neutral pH PDF after standardized initial training. We further analyzed
      the concentrations of 10 different glucose degradation products in Delflex
      Neutral pH PDF and compared the results with similar analyses in other
      commercially available biocompatible PDFs. RESULTS: All pH measurements (n = 288)
      in the delivered Delflex Neutral pH solution consistently fell within the labeled
      range of 7.0 +/- 0.4. Analysis of mixing errors showed no significant impact on
      the pH results. Delflex Neutral pH, Balance (Fresenius Medical Care, Bad Homburg,
      Germany), BicaVera (Fresenius Medical Care), and Gambrosol Trio (Gambro Lundia
      AB, Lund, Sweden) exhibited similar low total GDP concentrations, with maximums
      in the 4.25% solutions of 88 MUmol/L, 74 MUmol/L, 74 MUmol/L, and 79 MUmol/L
      respectively; the concentration in Physioneal (Baxter Healthcare Corporation,
      Deerfield, IL, USA) was considerably higher at 263.26 MUmol/L. The total GDP
      concentration in Extraneal (Baxter Healthcare Corporation) was 63 MUmol/L, being
      thus slightly lower than the concentrations in the 4.25% glucose solutions, but
      higher than the concentrations in the 1.5% and 2.5% glucose solutions.
      CONCLUSIONS: The new Delflex Neutral pH PDF consistently delivers neutral pH with
      minimal GDPs.

PMID- 22383634
TI  - Microdissection of Drosophila polytene chromosomes for DOP-PCR.
AB  - This protocol describes a method for the microdissection of Drosophila polytene
      chromosomes. The microdissected DNA can be amplified by degenerate
      oligonucleotide primed-polymerase chain reaction (DOP-PCR) and then used to
      prepare probes for fluorescent in situ hybridization (FISH).

PMID- 22383635
TI  - DOP-PCR amplification of probe DNA for whole-mount FISH in Drosophila.
AB  - It is sometimes useful to amplify DNA before labeling it. Degenerate
      oligonucleotide primed-polymerase chain reaction (DOP-PCR) allows amplification
      of any complex DNA, regardless of sequence. DOP-PCR is performed using a single
      primer that has a fixed sequence at its 5' end and several degenerate bases near
      its 3' end that allow it to anneal at low stringency to many sites in complex
      DNA. Following several PCR cycles with an annealing temperature of only 30
      degrees C, the annealing temperature is raised so that only products with the
      primer sequence at each end are amplified in the reaction. This protocol
      describes the use of DOP-PCR to amplify probe DNA for whole-mount fluorescent in
      situ hybridization (FISH) in Drosophila. Primary DOP-PCR amplification may be
      used for microdissected material, small volumes of melted gel slice, or small
      quantities of other DNA template. A procedure for secondary DOP-PCR amplification
      is also provided.

PMID- 22383636
TI  - Preparation and mounting of adult Drosophila structures in Canada balsam.
AB  - The Drosophila cuticle carries a rich array of morphological details. Thus,
      cuticle examination has had a central role in the history of genetics. To prepare
      fine "museum-quality," permanent slides, it is best to mount specimens in Canada
      Balsam. It is difficult to give precise recipes for Canada Balsam, because every
      user seems to prefer a slightly different viscosity. Dilute solutions spread
      easily and do not dry too rapidly while mounting specimens. The disadvantage is
      that there is actually less Balsam in a "drop" of the solution, and when dried,
      it can contract from the sides of the coverslip, sometimes disturbing the
      specimen. Unfortunately, there is no substitute for experience when using Canada
      Balsam. This protocol describes a procedure for mounting adult cuticles in Canada
      Balsam.

PMID- 22383637
TI  - Isolation and regeneration of protoplasts from Ectocarpus.
AB  - This article describes how to obtain isolated cells with no surrounding cell wall
      by enzymatic digestion of Ectocarpus filaments. The resultant protoplasts are
      totipotent and regenerate to produce individual algae under appropriate culture
      conditions. The yield of protoplasts and their capacity to regenerate are highly
      dependent on the Ectocarpus strain used, the stage of the life cycle, and the
      culture conditions. The highest yields are obtained with young gametophyte
      filaments cultivated at low density. The naked, wall-less cells produced by this
      protocol can be used for several applications, including studies of cell wall
      regeneration, investigation of the role of the cell wall in determining cell
      fate, and as a source of naked cells for the development of methods for
      introducing diverse molecules into the cell.

PMID- 22383638
TI  - Extraction of high-quality genomic DNA from Ectocarpus.
AB  - For some applications, such as genome sequencing and high-throughput genotyping
      with multiple markers, it is necessary to use high-quality genomic DNA. This
      article describes how to obtain several micrograms of high-quality, cesium
      chloride-purified DNA from 1 g of Ectocarpus filaments. We also recommend using
      DNA of this quality for quantitative RT-PCR control reactions. However, simpler,
      more rapid, kit-based methods are preferable for experiments that involve the
      treatment of large numbers of individuals, such as genotyping large populations
      with a small number of markers or PCR screening of large populations.

PMID- 22383633
TI  - Old and new perspectives on peritoneal dialysis in Italy emerging from the
      Peritoneal Dialysis Study Group Census.
AB  - BACKGROUND: To understand how peritoneal dialysis (PD) was being used in Italy in
      2005 and 2008, a census of all centers was carried out. METHODS: In 2005 and
      2008, data were collected from, respectively, 222 and 223 centers, with respect
      to 4432 and 4094 prevalent patients. RESULTS: In the two periods, the PD
      incidence remained stable (24.3% vs 22.9%), varying from center to center.
      Continuous ambulatory PD (CAPD) was the main initial method (55%), but APD was
      more widespread among prevalent patients (53%). Among patients returning to
      dialysis from transplantation (Tx), PD was used in 10%. The use of incremental
      CAPD increased significantly from 2005 to 2008, in terms both of the number of
      centers (27.0% vs 40.9%) and of patients (13.6% vs 25.7%). Late referrals
      remained stable at 28%, with less use of PD. The overall drop-out rate
      (episodes/100 patient-years) remained unchanged (31.0 vs 32.8), with 13.1 and
      12.9 being the result of death, and 11.8 and 12.4 being the result of a switch to
      hemodialysis, mainly after peritonitis. A dialysis partner was required by 21.8%
      of the PD patients. The incidence of peritonitis was 1 episode in 36.5 and 41.1
      patient-months, with negative cultures occurring in 17.1% of cases in both
      periods. The incidence of encapsulating peritoneal sclerosis (episodes/100
      patient-years) was 0.70, representing 1.26% of patients treated. The catheter
      types used and the sites and methods of insertion varied widely from center to
      center. CONCLUSIONS: These censuses confirm the good results of PD in Italy, and
      provide insight into little-known aspects such as the use of incremental PD, the
      presence of a dialysis partner, and the incidence of encapsulating peritoneal
      sclerosis.

PMID- 22383639
TI  - Immunostaining of Ectocarpus cells.
AB  - This article describes an immunostaining protocol for Ectocarpus that was
      optimized for the detection of tubulin but could be used with any suitable
      antibody. Ectocarpus has small but relatively transparent cells and the
      uniseriate filaments can be grown directly attached to the surface of microscope
      slides. These features make Ectocarpus particularly suitable for high resolution
      imaging approaches, both in vivo or after fixation. All incubations described
      below are carried out on a platform shaker at room temperature. Use high-quality
      microscope slides to avoid imperfections in the glass that can be a problem for
      confocal laserscan microscopy analysis.

PMID- 22383640
TI  - Construction and packaging of herpes simplex virus/adeno-associated virus
      (HSV/AAV) Hybrid amplicon vectors.
AB  - Herpes simplex virus type 1 (HSV-1)-based amplicon vectors conserve most
      properties of the parental virus: broad host range, the ability to transduce
      dividing and nondiving cells, and a large transgene capacity. This permits
      incorporation of genomic sequences as well as cDNA, large transcriptional
      regulatory sequences for cell-specific expression, multiple transgene cassettes,
      or genetic elements from other viruses. Hybrid vectors use elements from HSV-1
      that allow replication and packaging of large-vector DNA into highly infectious
      particles, and elements from other viruses that confer genetic stability to
      vector DNA in the transduced cell. For example, adeno-associated virus (AAV) has
      the unique ability to integrate its genome into a specific site on human
      chromosome 19. The viral rep gene and the inverted terminal repeats (ITRs) that
      flank the AAV genome are sufficient for this process. However, AAV-based vectors
      have a very small transgene capacity and do not conventionally contain the rep
      gene to support site-specific genomic integration. HSV/AAV hybrid vectors contain
      both HSV-1 replication and packaging functions and the AAV rep gene and a
      transgene cassette flanked by the AAV ITRs. This combines the large transgene
      capacity of HSV-1 with the capability of site-specific genomic transgene
      integration and long-term transgene expression of AAV. This protocol describes
      the preparation of HSV/AAV hybrid vectors using a replication
      competent/conditional, packaging-defective HSV-1 genome cloned as a bacterial
      artificial chromosome (BAC) to provide helper functions for vector replication
      and packaging. The advantages and limitations of such vectors compared to
      standard HSV-1 amplicon vectors are also discussed.

PMID- 22383641
TI  - Formation of solid lipid nanoparticle (SLN)-gene vector complexes for
      transfection of mammalian cells in vitro.
AB  - Solid lipid nanoparticles (SLNs) offer several technological advantages over
      standard DNA carriers such as cationic lipids or cationic polymers. However, in
      the absence of endosomolytic agents such as chloroquine, gene-transfer efficiency
      mediated by SLN-derived gene vectors consisting of optimized lipid composition
      remains lower compared to those achieved with standard transfection agents. This
      protocol describes the incorporation of a dimeric human immunodeficiency virus
      type-1 (HIV-1) TAT peptide into SLN gene vectors to increase gene-transfer
      efficiency. This results in higher transfection rates than for standard
      transfection agents in vitro; the ternary SLN-gene vector complexes usually
      result in transfection levels equal to or higher than those observed with gene
      vector complexes formulated with branched polyethylenimine (PEI) 25 kDa. One
      significant advantage of using this method is the low cytotoxicity of the SLN
      gene vectors. The application of the gene-transfer technique is limited to
      relatively low plasmid DNA (pDNA) concentrations of the resulting complexes (10
      ug/mL). At higher concentrations, the particles tend to aggregate and
      precipitate. Therefore, their use for in vivo application, which generally
      requires high pDNA concentrations, is limited.

PMID- 22383642
TI  - Scoring and analyzing aggression in Drosophila.
AB  - Aggression is an innate behavior that has likely evolved in the framework of
      defending or obtaining resources. This complex social behavior is influenced by
      genetic, hormonal, and environmental factors. In many organisms, aggression is
      critical to survival, but the ability to control and suppress aggression in
      distinct contexts also is necessary. Invertebrate organisms, with their
      relatively simple nervous systems and a multiplicity of powerful tools available
      to examine their often elaborate and complex behavioral displays, have become
      increasingly valuable models for investigating the genetic and systems biological
      roots of social behavior. In this protocol, we outline methods for analyzing
      aggression in Drosophila: The design encompasses eco-ethological constraints that
      emphasize an understanding of normal aggression. The details include steps for
      constructing a fight arena, isolating and painting flies, introducing flies to an
      arena, and videotaping and scoring fights. These experimental protocols are in
      current use to identify candidate genes important in aggression and to elaborate
      the neuronal circuitry underlying the display of aggression and other social
      behaviors.

PMID- 22383643
TI  - Interferometric detection of action potentials.
AB  - Individual action potentials in axons can be detected in vitro using intrinsic
      optical signals. The principles of this detection technique are described here.
      The technique has been demonstrated using neuronal axons dissected from lobster.
      It would also be applicable to axons and active dendrites of cultured neurons
      with diameters somewhat larger than an optical wavelength. Using index-matching
      techniques, it may be possible to extend the technique to smaller structures.

PMID- 22383644
TI  - In vivo labeling of cortical astrocytes with sulforhodamine 101 (SR101).
AB  - Fluorescent markers that stain particular cell types in the intact brain are
      essential tools for fluorescence microscopy because they enable studies of
      structure and function of cells identified in this way. Although cell type
      specific fluorescence staining can be achieved through promoter-driven expression
      of fluorescent proteins, this genetic approach is generally labor- and cost
      intensive. Alternative viral approaches for targeted fluorophore expression are
      relatively invasive. For astrocytes, there is a simple alternative. This protocol
      describes an easy and robust method for rapid (within minutes) and high-contrast
      staining of astrocytes in defined regions of the intact rodent cortex using the
      synthetic, water-soluble but non-fixable red fluorescent dye sulforhodamine 101
      (SR101). Selective staining is achieved through local uptake and gap junction
      mediated spread of SR101 following its topical application or injection into
      tissue. Applications, technical pitfalls, and limitations of the SR101-staining
      technique are discussed. Given its simplicity and reliability, SR101 staining is
      a valuable tool for the study of astrocyte function in the intact brain and for
      in vivo fluorescence microscopy in general.

PMID- 22383645
TI  - Introduction to genetic association studies.
AB  - Genetic association studies are used to find candidate genes or genome regions
      that contribute to a specific disease by testing for a correlation between
      disease status and genetic variation. This article provides a broad outline of
      the design and analysis of such studies, focusing on case-control studies in
      candidate genes or regions.

PMID- 22383646
TI  - Identifying cis-acting DNA elements within a control region.
AB  - Computational methods can be used to identify DNA sequence motifs that have been
      conserved through evolution, as well as motifs that correspond to recognition
      sites for known DNA-binding proteins. These computational methods, when combined
      with chromatin immunoprecipitation and other basic experiments, can provide
      preliminary insight into the elements and factors that regulate a gene of
      interest. When pursuing a more complete understanding of a control region of
      interest, a comprehensive mutant analysis should generally be performed as a
      critical step toward more advanced functional studies. This article describes
      strategies for such a comprehensive analysis. It also summarizes the insights
      provided by a comprehensive mutant analysis versus a phylogenetic analysis.

PMID- 22383647
TI  - Single-molecule imaging of stochastic signaling events in living cells.
AB  - Environmental changes result in signaling events at cell membranes. To develop
      the means to understand these events at the molecular level, it is essential to
      become familiar with the stochastic nature of signaling molecules in living
      cells. Using total internal reflection fluorescent microscopy (TIRFM), these
      signaling events can be directly observed at the single-molecule level. This
      article explains the basis of TIRFM and how it is set up. It then describes how
      to visualize cell membrane signaling events. It also explains how to prove that
      detected fluorescence is emitted from single dye molecules and how to analyze the
      data from TIRFM experiments.

PMID- 22383648
TI  - Preparation of chemotactically competent Dictyostelium cells.
AB  - Environmental changes result in signaling events in cell membranes. To develop
      the means to understand these events at the molecular level, it is essential to
      become familiar with the stochastic nature of signaling molecules in living
      cells. Using total internal reflection fluorescent microscopy (TIRFM), these
      signaling events can be directly observed at the single-molecule level. This
      protocol describes the preparation of chemotactically competent Dictyostelium
      cells. These cells are highly sensitive to chemoattractant stimulation and can be
      used to visualize single molecules with TIRFM.

PMID- 22383649
TI  - Preparation of an imaging chamber for visualizing single molecules in living
      Dictyostelium cells.
AB  - Environmental changes result in signaling events at cell membranes. To develop
      the means to understand these events at the molecular level, it is essential to
      become familiar with the stochastic nature of signaling molecules in living
      cells. Using total internal reflection fluorescent microscopy (TIRFM), these
      signaling events can be directly observed at the single-molecule level. This
      protocol describes the preparation of an imaging chamber to visualize single
      molecules in living Dictyostelium cells, which are highly sensitive to
      chemoattractant stimulation. It also describes treatment of the cells to allow
      visualization. Chemotactically competent cells are treated with the desired
      chemical, and the cell suspension is delivered onto coverslips and then overlaid
      with a thin agarose sheet in preparation for imaging. The cells are typically
      treated with a fluorescently labeled stimulant or inhibitor. Alternatively, the
      cells can be stimulated with photoreactive chemicals by using caged compounds. A
      caged compound is photoactivatable by irradiation with ultraviolet (UV) light,
      which cleaves a linker conjugating a caging moiety and a chemical. Thus, at a
      desired moment during recording of the single-molecule images, the concentration
      of the chemicals can be increased by photolysis of the caged compounds included
      in the buffer.

PMID- 22383650
TI  - Visualizing single molecules in living Dictyostelium cells using total internal
      reflection fluorescent microscopy (TIRFM).
AB  - Environmental changes result in signaling events at cell membranes. To develop
      the means to understand these events at the molecular level, it is essential to
      become familiar with the stochastic nature of signaling molecules in living
      cells. Using total internal reflection fluorescent microscopy (TIRFM), these
      signaling events can be directly observed at the single-molecule level. This
      protocol describes the procedure used for objective-type TIRFM to visualize
      single fluorescent molecules in living Dictyostelium cells, which are highly
      sensitive to chemoattractant stimulation. This method can also be applied to
      other cell types.

PMID- 22383651
TI  - General considerations for live imaging of developing hippocampal neurons in
      culture.
AB  - Dissociated cell cultures of the rodent hippocampus have become a standard model
      for studying many facets of neural development, including the development of
      polarity, axonal and dendritic growth, and synapse formation. The cultures are
      quite homogeneous--~90% of the cells are pyramidal neurons--and it is relatively
      easy to express green fluorescent protein (GFP)-tagged proteins by transfection.
      This article describes the cultures and the key features of the system used to
      image them. It also includes suggestions on labeling cells with GFP-tagged
      proteins. It concludes with a discussion of the advantages and disadvantages of
      this culture system.

PMID- 22383652
TI  - Long-term time-lapse imaging of developing hippocampal neurons in culture.
AB  - Dissociated cell cultures of the rodent hippocampus have become a standard model
      for studying many facets of neural development. The cultures are quite
      homogeneous and it is relatively easy to express green fluorescent protein (GFP)
      tagged proteins by transfection. Studying developmental processes that occur over
      many hours or days--for example, dendritic branching--involves capturing images
      of a cell at regular intervals without compromising cell survival. This approach
      is also useful for studying events of short duration that occur asynchronously
      across the cell population. For such studies, it is highly desirable to use a
      computer-controlled microscope with an automated stage, to follow multiple cells
      at different locations in the culture, moving sequentially from one to the next
      and capturing an image at each location. A method to correct for focal drift is
      also required. For long-term imaging, we culture neurons in a medium without
      phenol red, which is thought to give rise to toxic substances following exposure
      to light. To label cells with GFP-tagged proteins for long-term imaging, we
      usually use nucleofection (rather than lipid-mediated transfection); this gives a
      high transfection efficiency, which makes it easier to find the right cell for
      imaging. Our protocol for long-term imaging is given here, along with appropriate
      methods to express GFP-tagged proteins. Examples illustrate how the protocol can
      be used to image cytoskeletal dynamics during axon specification and to study
      kinesin motor dynamics in stage 2 neurons (when minor neurites extend).

PMID- 22383653
TI  - Short-term high-resolution imaging of developing hippocampal neurons in culture.
AB  - Dissociated cell cultures of the rodent hippocampus have become a standard model
      for studying many facets of neural development. The cultures are quite
      homogeneous and it is relatively easy to express green fluorescent protein (GFP)
      tagged proteins by transfection. Because the cultures are essentially two
      dimensional, there is no need to acquire images at multiple focal planes. For
      capturing rapid subcellular events at high resolution, as described here, one
      must maximize weak signals and reduce background fluorescence. Thus, these
      methods differ in several respects from those used for time-lapse imaging.
      Lipofectamine-mediated transfection yields a higher level of expression than does
      transfection with a nucleofection device. Images are usually collected with a
      spinning-disk confocal microscope, which improves the signal-to-noise ratio. In
      addition, we use an imaging medium designed to minimize background fluorescence
      rather than to enhance long-term cell survival. It is also important to select
      cultures at an appropriate stage of development. In our hands, lipofectamine
      based transfection works best on cells between 3 and 10 d after plating. GFP
      based fluorescence can be observed as early as 4 h after adding the DNA/lipid
      complexes to the cells, but expression usually increases over the next ~12 h and
      remains steady for days. The ratio of DNA to lipid is critical; to lower
      expression levels of the tagged construct, we use a combination of expression
      vector and empty plasmid, keeping the DNA amount constant. An example is included
      to illustrate the imaging of the microtubule-based vesicular transport of
      membrane proteins.

PMID- 22383655
TI  - Retraction of two articles.

PMID- 22383654
TI  - Inhibition of epithelial sodium channels and reduction of ciliary function in
      influenza.

PMID- 22383657
TI  - Ghent developmental balance test: a new tool to evaluate balance performance in
      toddlers and preschool children.
AB  - BACKGROUND: Balance is a fundamental component of movement. Early identification
      of balance problems is important to plan early intervention. The Ghent
      Developmental Balance Test (GDBT) is a new assessment tool designed to monitor
      balance from the initiation of independent walking to 5 years of age. OBJECTIVE:
      The purpose of this study was to establish the psychometric characteristics of
      the GDBT. METHODS: To evaluate test-retest reliability, 144 children were tested
      twice on the GDBT by the same examiner, and to evaluate interrater reliability,
      videotaped GDBT sessions of 22 children were rated by 3 different raters. To
      evaluate the known-group validity of GDBT scores, z scores on the GDBT were
      compared between a clinical group (n = 20) and a matched control group (n = 20).
      Concurrent validity of GDBT scores with the subscale standardized scores of the
      Movement Assessment Battery for Children-Second Edition (M-ABC-2), the Peabody
      Developmental Motor Scales-Second Edition (PDMS-2), and the balance subscale of
      the Bruininks-Oseretsky Test-Second Edition (BOT-2) was evaluated in a combined
      group of the 20 children from the clinical group and 74 children who were
      developing typically. RESULTS: Test-retest and interrater reliability were
      excellent for the GDBT total scores, with intraclass correlation coefficients of
      .99 and .98, standard error of measurement values of 0.21 and 0.78, and small
      minimal detectable differences of 0.58 and 2.08, respectively. The GDBT was able
      to distinguish between the clinical group and the control group (t(38) = 5.456,
      P<.001). Pearson correlations between the z scores on GDBT and the standardized
      scores of specific balance subscales of the M-ABC-2, PDMS-2, and BOT-2 were
      moderate to high, whereas correlations with subscales measuring constructs other
      than balance were low. CONCLUSIONS: The GDBT is a reliable and valid clinical
      assessment tool for the evaluation of balance in toddlers and preschool-aged
      children.

PMID- 22383658
TI  - Ultrasonographic assessment of humeral retrotorsion in baseball players: a
      validation study.
AB  - BACKGROUND: Recently, clinicians and researchers started using diagnostic
      ultrasound to measure humeral torsion as an alternative to radiological
      assessments in overhead-throwing athletes and other clinical populations.
      Ultrasound appears to be a reliable, nonradiological alternative, but ultrasound
      assessment has not been validated against computed tomography (CT), the current
      gold standard. PURPOSE: This study aimed to establish the validity of an
      ultrasound assessment of humeral torsion by comparing data obtained using both
      ultrasound and CT, the current standard. STUDY DESIGN: Cohort study (Diagnosis);
      Level of evidence, 2. METHODS: Humeral torsion was measured using both ultrasound
      and CT in 24 collegiate-aged baseball players. Comparisons between the
      assessments were made using both regression and Bland-Altman plots. Reliability
      and precision were also established. RESULTS: A strong relationship existed
      between humeral torsion variables obtained with ultrasound and CT (R = .797, R
      (2) = .635, P < .001). The ultrasound assessment yielded reliability coefficients
      ranging from .991 to .997, with approximately 1 degrees  of measurement error.
      The CT method's reliability coefficients ranged from .805 to .933, with
      approximately 3.5 degrees  of measurement error. CONCLUSION: There was a strong
      relationship between humeral torsion obtained with ultrasound and CT, the current
      standard of assessment. Ultrasound provides a reliable, valid alternative to CT
      for obtaining an indication of the amount of humeral torsion in the upper
      extremity.

PMID- 22383659
TI  - Dynamic sagittal plane trunk control during anterior cruciate ligament injury.
AB  - BACKGROUND: Recent studies have demonstrated that trunk control likely plays a
      role in anterior cruciate ligament (ACL) injury. Yet, the majority of ACL
      research remains focused on the lower limb, with limited information on the trunk
      position at the time of injury. HYPOTHESES: Athletes experiencing a noncontact
      ACL injury after a 1-legged landing position their center of mass (COM) more
      posterior from the base of support (BOS) at initial ground contact in comparison
      with uninjured athletes. The distance from the COM to the BOS (COM_BOS) is larger
      in female, as compared with male, athletes during 1-legged landing. STUDY DESIGN:
      Case control study; Level of evidence, 3. METHODS: Movie captures of 20 athletes
      performing a 1-legged landing maneuver resulting in a torn ACL were compared with
      matched (for gender, sport, and activity just before landing) movie captures of
      20 athletes performing a similar maneuver that did not result in an ACL
      disruption (controls). The COM_BOS, trunk(G) angle, and limb(G) angle (both
      relative to the gravity vector) were measured in the sagittal plane at initial
      ground-foot contact. A 2-way ANOVA (injury status * gender) was used to examine
      the hypotheses. RESULTS: There was a significant difference in all 3 measures
      based on injury status but not on gender. The COM_BOS, normalized by femur
      length, and limb(G) angle were greater (Delta = 0.9, P < .001 and Delta = 16
      degrees , P = .004, respectively), and the trunk(G) angle was smaller (Delta = 12
      degrees , P = .016) in the participants who sustained an ACL injury as compared
      with controls. The average COM was calculated as 38 cm more posterior relative to
      the BOS in the participants who sustained an ACL injury as compared with
      controls. CONCLUSION: Landing with the COM far posterior to the BOS may be a risk
      factor for noncontact ACL injury and potentially can be addressed in prevention
      programs.

PMID- 22383660
TI  - Acute pulmonary admissions following implementation of a national workplace
      smoking ban.
AB  - BACKGROUND: The implementation of workplace smoking bans has contributed to a
      significant reduction in the incidence of acute coronary syndrome admissions, but
      their influence on adult acute pulmonary disease admissions is unclear. We sought
      to assess the impact of a national smoking ban on nationwide admissions of
      individuals of working age with acute pulmonary illness. METHODS: Data relating
      to emergency hospital admissions of subjects aged 20 to 70 years preceding and
      succeeding the implementation of the Irish smoking ban were obtained from a
      central registry. Population, weather, pollution, and influenza data were
      obtained from the relevant authorities. Poisson regression analysis was used to
      assess adjusted risk of emergency hospital admission following implementation of
      the smoking ban. RESULTS: Overall admissions with pulmonary illness decreased
      from 439 per 100,000 population per annum to 396 per 100,000 population per annum
      following the ban (unadjusted relative risk [RR], 0.91; 95% CI, 0.83-0.99; P =
      .048). This persisted following adjustment for confounding factors (adjusted RR,
      0.85; 95% CI, 0.72-0.99; P = .04) and was most marked among younger age groups
      and in admissions due to asthma (adjusted RR, 0.60; 95% CI, 0.39-0.91; P = .016).
      Admissions with acute coronary syndromes (adjusted RR, 0.82; 95% CI, 0.70-0.97; P
      = .02), but not stroke (adjusted RR, 0.93; 95% CI, 0.73-1.20; P = .60), were also
      reduced. CONCLUSIONS: The implementation of a nationwide workplace smoking ban is
      associated with a decline in admissions with acute pulmonary disease among
      specific age groups and an overall reduction in asthma admissions. This may
      result from reduced exposure of vulnerable individuals to environmental tobacco
      smoke, emphasizing the potential benefit of legislation reducing second-hand
      smoke exposure.

PMID- 22383661
TI  - Artificial stone silicosis [corrected]: disease resurgence among artificial stone
      workers.
AB  - BACKGROUND: Silicosis is a progressive, fibrotic, occupational lung disease
      resulting from inhalation of respirable crystalline silica. This disease is
      preventable through appropriate workplace practices. We systematically assessed
      an outbreak of silicosis among patients referred to our center for lung
      transplant. METHODS: This retrospective cohort analysis included all patients
      with a diagnosis of silicosis who were referred for evaluation to the National
      Lung Transplantation Program in Israel from January 1997 through December 2010.
      We also compared the incidence of lung transplantation (LTX) due to silicosis in
      Israel with that of the International Society for Heart and Lung Transplantation
      (ISHLT) registry. RESULTS: During the 14-year study period, 25 patients with
      silicosis were referred for evaluation, including 10 patients who went on to
      undergo LTX. All patients were exposed by dry cutting a relatively new,
      artificial, decorative stone product with high crystalline silica content used
      primarily for kitchen countertops and bathroom fixtures. The patients had
      moderate-to-severe restrictive lung disease. Two patients developed progressive
      massive fibrosis; none manifested acute silicosis (silicoproteinosis). Three
      patients died during follow-up, without LTX. Based on the ISHLT registry
      incidence, 0.68 silicosis cases would have been expected instead of the 10
      observed (incidence ratio, 14.6; 95% CI, 7.02-26.8). CONCLUSIONS: This silicosis
      outbreak is important because of the worldwide use of this and similar high
      silica-content, artificial stone products. Further cases are likely to occur
      unless effective preventive measures are undertaken and existing safety practices
      are enforced.

PMID- 22383662
TI  - Predictors of in-hospital vs postdischarge mortality in pneumonia.
AB  - BACKGROUND: Many patients who die within 30 days of admission to the hospital for
      pneumonia die after discharge. Recently, 30-day mortality for patients with
      pneumonia became a publicly reported performance measure, meaning that hospitals
      are, in part, being measured based on how the patient fares after discharge from
      the hospital. This study was undertaken to determine which factors predict in
      hospital vs postdischarge mortality in patients with pneumonia. METHODS: This was
      a retrospective analysis of a database of 21,223 patients on Medicare aged 65
      years and older admitted to the hospital between 2000 and 2001. Multivariate
      logistic regression analyses were performed to determine the association between
      26 patient characteristics and the timing of death (in-hospital vs postdischarge)
      among those patients who died within 30 days of hospital admission. RESULTS:
      Among the 21,223 patients, 2,561 (12.1%) died within 30 days of admission: 1,343
      (52.4%) during the hospital stay, and 1,218 (47.6%) after discharge. Multivariate
      logistic regression demonstrated that seven factors were significantly associated
      with death prior to discharge: systolic BP < 90 mm Hg, respiration rate > 30/min,
      bacteremia, arterial pH < 7.35, BUN level > 11 mmol/L, arterial Po(2) < 60 mm Hg
      or arterial oxygen saturation < 90%, and need for mechanical ventilation. Some
      underlying comorbidities were associated with a nonstatistically significant
      trend toward death after discharge. CONCLUSIONS: Of elderly patients dying within
      30 days of admission to the hospital, approximately one-half die after discharge
      from the hospital. Comorbidities, in general, were equally associated with death
      in the hospital and death after discharge

PMID- 22383664
TI  - Usefulness of preemptive anticoagulation in patients with suspected pulmonary
      embolism: a decision analysis.
AB  - BACKGROUND: The diagnostic workup of pulmonary embolism (PE) may take several
      hours. The usefulness of anticoagulant treatment while awaiting the results of
      diagnostic tests has not been assessed. The objective of this study was to
      compare the risks and benefits of bid low-molecular-weight heparin vs no
      treatment in patients with suspected PE. METHODS: We developed a decision tree
      with the following outcomes: mortality related to untreated and treated PE,
      mortality due to major hemorrhage, and intracranial bleeding. The timeframe
      extended from the suspicion of PE to its confirmation or exclusion. Most
      probabilities were derived from data from the Computerized Registry of Patients
      with VTE (RIETE). We estimated the incidence of bleeding by categories of
      clinical prediction rules of PE from a recent diagnostic management study of PE.
      Uncertainty was assessed through one-way and probabilistic sensitivity analyses.
      RESULTS: The model favored preemptive anticoagulation if the diagnostic delay was
      > 6.3 h, > 2.3 h, and > 0.3 h (Revised Geneva low, intermediate, and high
      probability) and > 8.1 h and > 1.7 h (Wells unlikely and likely). With a
      diagnostic delay of 6 h, the absolute mortality reduction with anticoagulation
      was 0%, 0.02%, and 0.1% for low, intermediate, and high clinical probability,
      respectively. In one-way sensitivity analyses, the mortality of untreated PE was
      the most critical variable. Probabilistic analyses reinforced the superiority of
      anticoagulation in intermediate- and high-probability patients and suggested that
      low-probability patients might not benefit from treatment after diagnostic delays
      of < 6 to 8 h. CONCLUSIONS: Our model suggests that patients with intermediate
      and high/likely probabilities of PE benefit from preemptive anticoagulation. With
      a low probability, the decision to treat may rely on the expected diagnostic
      delay.

PMID- 22383663
TI  - MicroRNA-199a-5p is associated with hypoxia-inducible factor-1alpha expression in
      lungs from patients with COPD.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene
      expression posttranscriptionally, and their impact on gene expression has been
      reported in various diseases. It has been reported that the expression of the
      hypoxia-inducible factor-1alpha (HIF-1alpha) is reduced and that of p53 is
      increased in lungs from patients with COPD. However, the role of miRNAs
      associated with these genes in lungs from patients with COPD is unknown. METHODS:
      Lung tissue samples from 55 patients were included in this study. Total RNA,
      miRNA, and protein were extracted from lung tissues and used for reverse
      transcriptase polymerase chain reaction and Western blot analysis. Cell culture
      experiments were performed using cultured human pulmonary microvascular
      endothelial cells (HPMVECs). RESULTS: miR-34a and miR-199a-5p expressions were
      increased, and the phosphorylation of AKT was decreased in the lung tissue
      samples of patients with COPD. The miR-199a-5p expression was correlated with HIF
      1alpha protein expression in the lungs of patients with COPD. Transfection of
      HPMVECs with the miR-199a-5p precursor gene decreased HIF-1alpha protein
      expression, and transfection with the miR-34a precursor gene increased miR-199a
      5p expression. CONCLUSIONS: These data suggest that miR-34a and miR-199a-5p
      contribute to the pathogenesis of COPD, and these miRNAs may also affect the HIF
      1alpha-dependent lung structure maintenance program.

PMID- 22383665
TI  - ADRB2 polymorphisms and budesonide/formoterol responses in COPD.
AB  - BACKGROUND: Effects of beta(2)-adrenergic receptor gene (ADRB2) polymorphism on
      therapeutic responses to long-acting beta(2)-adrenergic agonists have not been
      evaluated in long-term COPD trials. We aimed to investigate the effects of the
      ADRB2 Gly16Arg polymorphism on response to formoterol alone or in combination
      with the inhaled corticosteroid budesonide in patients with COPD. METHODS:
      Patients >= 40 years of age with moderate to very severe COPD from the 12-month
      trial I (NCT00206167) or the 6-month trial II (NCT00206154) were randomly
      assigned to bid budesonide/formoterol pressurized metered-dose inhaler (pMDI)
      320/9 MUg or 160/9 MUg, budesonide pMDI 320 MUg + formoterol dry powder inhaler 9
      MUg (trial II), budesonide pMDI 320 MUg (trial II), formoterol dry powder inhaler
      9 MUg, or placebo. The effect of Gly16Arg on predose FEV(1) and 1-h postdose
      FEV(1), exacerbations, diary variables, and adverse events were analyzed.
      RESULTS: No significant interaction between genotype and treatment response was
      observed for predose (P >= .197) or postdose FEV(1) (P >= .125) in either
      pharmacogenetic study (n = 2,866). The number of COPD exacerbations per patient
      treatment year was low and similar across genotypes for the active treatment
      groups (both studies). Percentages of patients with adverse events were similar
      across Gly16Arg genotype groups for each treatment. CONCLUSION: Therapeutic
      response and tolerability to long-term treatment with formoterol alone or in
      combination with budesonide was not modified by ADRB2 Gly16Arg genotype in two
      large independent pharmacogenetic studies in patients with moderate to very
      severe COPD.

PMID- 22383666
TI  - Comparison of indacaterol with tiotropium or twice-daily long-acting beta 
      agonists for stable COPD: a systematic review.
AB  - BACKGROUND: Bronchodilators are central to the symptomatic management of patients
      with COPD.Previous data have shown that inhaled indacaterol improved numerous
      clinical outcomes over placebo. METHODS: This systematic review explored the
      efficacy and safety of indacaterol in comparison with tiotropium or bid long
      acting beta 2 -agonists (TD-LABAs) for treatment of moderate to severe COPD.
      Randomized controlled trials were identified after a search of different
      databases of published and unpublished trials. RESULTS: Five trials (5,920
      participants) were included. Compared with tiotropium, indacaterol showed
      statistically and clinically significant reductions in the use of rescue
      medication and dyspnea(43% greater likelihood of achieving a minimal clinically
      important difference [MCID] in the transitional dyspnea index [TDI]; number
      needed to treat for benefit [NNTB] 5 10). Additionally,the MCID in health status
      was more likely to be achieved with indacaterol than with tiotropium (OR = 1.43;
      95% CI, 1.22-1.68; P = .00001; [NNTB ]= 10). Trough FEV 1 was significantly
      higher at the end of treatment with indacaterol than with TD-LABAs (80 mL, P =
      .00001). Similarly, indacaterol signifi cantly improved dyspnea (61% greater
      likelihood of achieving an MCID in TDI, P = .008) and health status (21% greater
      likelihood of achieving an MCID in St. George's Respiratory Questionnaire, P 5
      .04) than TD-LABA. Indacaterol showed similar levels of safety and tolerability
      to both comparators. CONCLUSIONS: Available evidence suggests that indacaterol
      may prove useful as an alternative to tiotropium or TD-LABA due to its effects on
      health status, dyspnea, and pulmonary function.

PMID- 22383667
TI  - The association between sepsis and potential medical injury among hospitalized
      patients.
AB  - BACKGROUND: Patient safety remains a national priority, but the role of disease
      specific characteristics in safety is not well characterized. METHODS: We
      identified potentially preventable medical injuries using patient safety
      indicators (PSIs) and annual data from the Nationwide Inpatient Sample between
      2003 and 2007. We compared the rate of selected PSIs among patients hospitalized
      with and without sepsis. Among patients with sepsis, we also compared PSI rates
      across severity strata. Using multivariable case-control matching and regression
      analyses, we estimated the excess adverse outcomes associated with PSI events in
      patients with sepsis. RESULTS: Patients hospitalized with sepsis accounted for 2%
      to 4% of hospital discharges; however, they accounted for 9% to 26% of all
      potential medical injuries. PSI rates varied considerably; among patients
      hospitalized for sepsis, they were lowest for accidental puncture or laceration
      and highest for postoperative respiratory failure. Nearly all PSI rates were
      higher among patients with sepsis compared with patients without sepsis. Among
      those with sepsis, most PSI rates increased as sepsis severity increased.
      Compared with matched sepsis control subjects, increased length of stay and
      hospital charges were associated with PSI events in sepsis cases. However, only
      decubitus ulcer, iatrogenic pneumothorax, and postoperative metabolic and
      physiologic derangement or respiratory failure were associated with excess
      mortality. CONCLUSION: Patients hospitalized for sepsis, compared with the
      general hospital population, were at a substantially increased risk of potential
      medical injury; their risk rose as disease severity increased. Future patient
      safety efforts may benefit from focusing on medically vulnerable populations.

PMID- 22383670
TI  - Transesophageal echocardiography-assisted management of hypoxemia in a patient
      with biventricular support.

PMID- 22383668
TI  - Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del
      CFTR mutation.
AB  - BACKGROUND: Ivacaftor (VX-770) is a cystic fibrosis transmembrane conductance
      regulator (CFTR) potentiator that was approved in the United States for the
      treatment of cystic fibrosis (CF) in patients >= 6 years of age who have a G551D
      mutation; however, the most prevalent disease-causing CFTR mutation, F508del,
      causes a different functional defect. The objectives of this study were to
      evaluate the safety of ivacaftor in a larger population and for a longer time
      period than tested previously and to assess the efficacy of ivacaftor in subjects
      with CF who are homozygous for F508del-CFTR. METHODS: This was a phase 2 study
      with a 16-week randomized (4:1), double-blind, placebo-controlled period (part A)
      and an open-label extension (part B) for subjects who met prespecified criteria.
      RESULTS: Part A: The safety profile of ivacaftor was comparable to that of the
      placebo. The overall adverse event frequency was similar in the ivacaftor (87.5%)
      and placebo (89.3%) groups through 16 weeks. The difference in the change of FEV1
      % predicted from baseline through week 16 (primary end point) between the
      ivacaftor and placebo groups was 1.7% (P = .15). Sweat chloride, a biomarker of
      CFTR activity, showed a small reduction in the ivacaftor vs placebo groups of 
      2.9 mmol/L (P = .04) from baseline through week 16. Part B: No new safety signals
      were identified. The changes in FEV1 or sweat chloride in part A were not
      sustained with ivacaftor treatment from week 16 to week 40. CONCLUSIONS: These
      results expand the safety information for ivacaftor and support its continued
      evaluation. Lack of a clinical effect suggests that a CFTR potentiator alone is
      not an effective therapeutic approach for patients who have CF and are homozygous
      for F508del-CFTR. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00953706; URL:
      www.clinicaltrials.gov.

PMID- 22383669
TI  - In vivo platelet activation in critically ill patients with primary 2009
      influenza A(H1N1).
AB  - BACKGROUND: Changes in platelet reactivity during 2009 influenza A(H1N1)
      (A[H1N1]) have not been characterized. METHODS: We prospectively examined
      platelet activation and cytokine responses in patients with A(H1N1) (n = 20),
      matched patients with bacterial pneumonia (n = 15), and nonhospitalized, healthy
      control subjects (n = 10). RESULTS: Platelet-monocyte aggregation was higher in
      patients with A(H1N1) (21.4% +/- 4.7%) compared with patients with pneumonia
      (10.9% +/- 3.7%) and control subjects (8.1% +/- 4.5%, P < .05). Similarly, PAC-1
      (antibody that binds to the active conformation of integrin alpha(IIb)beta(3))
      binding to platelets is increased in patients with A(H1N1) (9.5% +/- 4.7%)
      compared with patients with pneumonia (1.0% +/- 0.7%) and healthy subjects (0.61%
      +/- 0.15%, P < .10). PAC-1 binding was twofold higher in patients with A(H1N1)
      with shock vs those without shock. IL-6 levels were elevated in patients with
      A(H1N1), indicating systemic inflammation consistent with activation of
      circulating platelets. CONCLUSIONS: These findings, derived from a small but
      documented cohort of patients, demonstrate that platelet activation responses
      during A(H1N1) are enhanced-exceeding responses in patients with bacterial
      pneumonia-and provide new evidence that platelets may contribute to inflammatory
      responses during A(H1N1).

PMID- 22383671
TI  - The volatile anesthetic isoflurane prevents ventilator-induced lung injury via
      phosphoinositide 3-kinase/Akt signaling in mice.
AB  - BACKGROUND: Mechanical ventilation leads to ventilator-induced lung injury in
      animals, and can contribute to acute lung injury/acute respiratory distress
      syndrome in humans. Acute lung injury/acute respiratory distress syndrome
      currently causes an unacceptably high rate of morbidity and mortality among
      critically ill patients. Volatile anesthetics have been shown to exert anti
      inflammatory and organ-protective effects in vivo. We investigated the effects of
      the volatile anesthetic isoflurane on lung injury during mechanical ventilation.
      METHODS: C57BL/6N mice were ventilated with a tidal volume of 12 mL/kg body
      weight for 6 hours in the absence or presence of isoflurane, and, in a second
      series, with or without the specific phosphoinositide 3-kinase/Akt inhibitor
      LY294002. Lung injury was determined by comparative histology, and by the
      isolation of bronchoalveolar lavage for differential cell counting and analysis
      of cytokine levels using enzyme-linked immunosorbent assays. Lung homogenates
      were analyzed for protein expression by Western blotting. RESULTS: Mechanical
      ventilation caused increases in alveolar wall thickening, cellular infiltration,
      and an elevated ventilator-induced lung injury score. Neutrophil influx and
      cytokine (i.e., interleukin-1beta, and macrophage inflammatory protein-2) release
      were enhanced in the bronchoalveolar lavage of ventilated mice. The expression
      levels of the stress proteins hemeoxygenase-1 and heat shock protein-70 were
      elevated in lung tissue homogenates. Isoflurane ventilation significantly reduced
      lung damage, inflammation, and stress protein expression. In contrast,
      phosphorylation of Akt protein was substantially increased during mechanical
      ventilation with isoflurane. Inhibition of phosphoinositide 3-kinase/Akt
      signaling before mechanical ventilation completely reversed the lung-protective
      effects of isoflurane treatment in vivo. CONCLUSIONS: Inhalation of isoflurane
      during mechanical ventilation protects against lung injury by preventing
      proinflammatory responses. This protection is mediated via phosphoinositide 3
      kinase/Akt signaling.

PMID- 22383672
TI  - Inhibition of alpha5 gamma-Aminobutyric acid type A receptors restores
      recognition memory after general anesthesia.
AB  - BACKGROUND: General anesthetics cause cognitive deficits that persist much longer
      than would be expected on the basis of their pharmacokinetics. The cellular
      mechanisms underlying these postanesthetic cognitive deficits remain unknown.
      gamma-Aminobutyric acid type A (GABA(A)) receptors are principal targets for most
      anesthetics. In particular, the alpha5GABA(A) receptor subtype has been
      implicated in acute memory blockade during anesthesia and memory deficits in the
      early postoperative period. We first sought to determine whether working memory
      and short-term recognition memory are impaired after isoflurane anesthesia. The
      second aim of the study was to determine whether memory deficits after isoflurane
      can be reversed by inhibiting alpha5GABA(A) receptors. We also sought to
      determine whether the expression of alpha5GABA(A) receptors is necessary for the
      development of memory dysfunction after isoflurane. Lastly, the effect of
      sevoflurane on memory was studied. METHODS: Wild-type and alpha5GABA(A) receptor
      null-mutant (Gabra5-/-) mice were treated with isoflurane (1.3%; 1 minimum
      alveolar concentration [MAC]) or sevoflurane (2.3%; 1 MAC) or vehicle gas for 1
      hour. Memory performance was assessed with a novel object recognition task. Mice
      were trained on the recognition task either 24 hours or 72 hours after isoflurane
      anesthesia. Working memory and short-term memory were tested 1 minute and 1 hour
      after training, respectively. To determine whether inhibition of alpha5GABA(A)
      receptors reverses memory deficits, we treated a subset of mice with L-655,708
      (0.35 mg/kg or 0.7 mg/kg) 23.5 hours after isoflurane and 30 minutes before
      behavioral training. RESULTS: Short-term memory was impaired in wild-type mice 24
      hours after isoflurane as evidenced by a decrease in the discrimination ratio
      (control 0.66 +/- 0.03 vs isoflurane 0.51 +/- 0.03, P = 0.0005). In contrast,
      working memory was not impaired by isoflurane (control 0.68 +/- 0.05 vs
      isoflurane 0.67 +/- 0.04, P = 0.979). The deficit in short-term memory was fully
      reversed by L-655,708 (effect of isoflurane * L-655,708, F(2,102) = 3.59, P =
      0.032; isoflurane 0.51 +/- 0.03 vs isoflurane + L-655,708 at 0.35 mg/kg 0.67 +/-
      0.03, P < 0.05). By 72 hours, the deficits in short-term memory resolved
      spontaneously (control 0.65 +/- 0.05 vs isoflurane 0.60 +/- 0.04, P = 0.441).
      Gabra5-/- mice showed no short-term memory deficits 24 hours after isoflurane
      (effect of isoflurane F(1,47) = 0.375, P = 0.544). Sevoflurane also caused memory
      deficits 24 hours after anesthesia, as evidence by a reduction in the
      discrimination ratio (control 0.63 +/- 0.02 vs sevoflurane 0.53 +/- 0.03, P =
      0.039). CONCLUSIONS: Inhalational anesthetics cause deficits in anterograde
      recognition memory. This proof-of-concept study shows that alpha5GABA(A)
      receptors are necessary for the development of postanesthetic deficits in
      recognition memory and that these receptors can be targeted to restore memory
      even after the anesthetic has been eliminated.

PMID- 22383673
TI  - Rationale of dead space measurement by volumetric capnography.
AB  - Dead space is the portion of a tidal volume that does not participate in gas
      exchange because it does not get in contact with blood flowing through the
      pulmonary capillaries. It is commonly calculated using volumetric capnography,
      the plot of expired carbon dioxide (CO(2)) versus tidal volume, which is an easy
      bedside assessment of the inefficiency of a particular ventilatory setting.
      Today, Bohr's original dead space can be calculated in an entirely noninvasive
      and breath-by-breath manner as the mean alveolar partial pressure of CO(2)
      (Paco(2)) which can now be determined directly from the capnogram. The value
      derived from Enghoff's modification of Bohr's formula (using Paco(2) instead of
      PACO(2)) is a global index of the inefficiency of gas exchange rather than a true
      "dead space" because it is influenced by all causes of ventilation/perfusion
      mismatching, from real dead space to shunt. Therefore, the results obtained by
      Bohr's and Enghoff's formulas have different physiological meanings and
      clinicians must be conscious of such differences when interpreting patient data.
      In this article, we describe the rationale of dead space measurements by
      volumetric capnography and discuss its main clinical implications and the
      misconceptions surrounding it.

PMID- 22383674
TI  - The Diesel Exhaust in Miners Study: V. Evaluation of the Exposure Assessment
      Methods.
AB  - Exposure to respirable elemental carbon (REC), a component of diesel exhaust
      (DE), was assessed for an epidemiologic study investigating the association
      between DE and mortality, particularly from lung cancer, among miners at eight
      mining facilities from the date of dieselization (1947-1967) through 1997. To
      provide insight into the quality of the estimates for use in the epidemiologic
      analyses, several approaches were taken to evaluate the exposure assessment
      process and the quality of the estimates. An analysis of variance was conducted
      to evaluate the variability of 1998-2001 REC measurements within and between
      exposure groups of underground jobs. Estimates for the surface exposure groups
      were evaluated to determine if the arithmetic means (AMs) of the REC measurements
      increased with increased proximity to, or use of, diesel-powered equipment, which
      was the basis on which the surface groups were formed. Estimates of carbon
      monoxide (CO) (another component of DE) air concentrations in 1976-1977, derived
      from models developed to predict estimated historical exposures, were compared to
      1976-1977 CO measurement data that had not been used in the model development.
      Alternative sets of estimates were developed to investigate the robustness of
      various model assumptions. These estimates were based on prediction models using:
      (i) REC medians rather AMs, (ii) a different CO:REC proportionality than a 1:1
      relation, and (iii) 5-year averages of historical CO measurements rather than
      modeled historical CO measurements and DE-related determinants. The analysis of
      variance found that in three of the facilities, most of the between-group
      variability in the underground measurements was explained by the use of job
      titles. There was relatively little between-group variability in the other
      facilities. The estimated REC AMs for the surface exposure groups rose overall
      from 1 to 5 MUg m(-3) as proximity to, and use of, diesel equipment increased.
      The alternative estimates overall were highly correlated (~0.9) with the primary
      set of estimates. The median of the relative differences between the 1976-1977 CO
      measurement means and the 1976-1977 estimates for six facilities was 29%.
      Comparison of estimated CO air concentrations from the facility-specific
      prediction models with historical CO measurement data found an overall agreement
      similar to that observed in other epidemiologic studies. Other evaluations of
      components of the exposure assessment process found moderate to excellent
      agreement. Thus, the overall evidence suggests that the estimates were likely
      accurate representations of historical personal exposure levels to DE and are
      useful for epidemiologic analyses.

PMID- 22383675
TI  - Reduced serum IgG responses to pneumococcal antigens in otitis-prone children may
      be due to poor memory B-cell generation.
AB  - A low level of serum antibody to antigens expressed by Streptococcus pneumoniae
      has been proposed to explain the susceptibility of children to recurrent episodes
      of acute otitis media (hereafter, "otitis-prone children"). By use of enzyme
      linked immunospot assays, the percentages of memory B cells to pneumococcal
      protein antigens PhtD, LytB, PcpA, PhtE, and Ply were compared between otitis
      prone and non-otitis-prone children at the time of acute otitis media or
      nasopharyngeal colonization with S. pneumoniae. We found significantly lower
      percentages of memory B cells to 3 pneumococcal protein antigens (PhtD, PhtE, and
      Ply) and reduced antigen-specific immunoglobulin G concentrations in otitis-prone
      children, compared with non-otitis-prone children.

PMID- 22383676
TI  - Gene polymorphism in toll-like receptor 4: effect on antibody production and
      persistence after acellular pertussis vaccination during adolescence.
AB  - BACKGROUND: Toll-like receptors play an important role in the regulation of
      adaptive immunity. This study aimed to investigate whether Toll-like receptor 4
      (TLR4) polymorphisms influence the production and persistence of antibodies after
      acellular pertussis booster vaccination during adolescence. METHODS: Seventy-five
      subjects received a single dose of diphtheria and tetanus toxoids and acellular
      pertussis vaccine 10 years ago, during adolescence. The same cohort was followed
      up at 3, 5, and 10 years after this booster vaccination. Pyrosequencing was used
      for detecting polymorphism in TLR4. Concentrations of anti-pertussis vaccine
      antibodies were measured by standardized enzyme-linked immunosorbant assay and
      published elsewhere. RESULTS: The fold increase in antibodies to pertussis toxin
      after original vaccination 10 years ago was significantly lower in subjects with
      TLR4 polymorphism than in those without (55% vs 86%; P = .028). At the 3-year
      follow-up evaluation, geometric mean concentrations of anti-pertussis vaccine
      antibodies were significantly lower in subjects with TLR4 polymorphism, compared
      with those without the polymorphism (for pertussis toxin, P = .028; for
      filamentous hemagglutinin, P = .047; and for pertactin, P = .046). CONCLUSIONS:
      This study suggests that TLR4 Asp299Gly polymorphism might influence production
      and persistence of antibodies after pertussis booster vaccination in adolescents.
      However, the results should be interpreted with caution as the number of subjects
      included in this study was limited.

PMID- 22383677
TI  - Platelet apoptosis and apoptotic platelet clearance by macrophages in secondary
      dengue virus infections.
AB  - BACKGROUND: The mechanisms of thrombocytopenia and platelet phagocytosis in
      dengue illness are not fully understood. METHODS: A prospective hospital-based
      study was conducted to examine the relationships between platelet counts, serum
      thrombopoietin (TPO) levels, and platelet apoptosis and phagocytosis in 81
      patients with secondary dengue virus (DV) infections and 38 healthy volunteers.
      The apoptosis and phagocytosis of cultured platelets after exposure to DV were
      also examined. RESULTS: Platelet apoptosis, platelet phagocytosis, and serum TPO
      levels were increased significantly in patients during the acute and early
      convalescence phases compared with levels observed in patients during the
      convalescence phase and in healthy volunteers. A significant correlation between
      platelet apoptosis and platelet phagocytosis was also observed in these patients.
      Platelet phagocytosis was inhibited significantly by the D89E mutant, which
      carries a point mutation in the RGD motif of milk fat globule-epidermal growth
      factor 8, a phosphatidylserine-recognizing bridge molecule. DV-induced platelet
      apoptosis and increased phagocytosis of DV-induced apoptotic platelets was
      confirmed using in vitro assays. CONCLUSIONS: Our data suggest an increased
      phagocytosis of DV-induced apoptotic platelets by macrophages via a
      phosphatidylserine-recognizing pathway in secondary DV infection. Accelerated
      platelet clearance, however, was overcome by TPO-induced enhanced thrombopoiesis
      in these patients. CLINICAL TRIALS REGISTRATION: UMIN000004835.

PMID- 22383678
TI  - Cytomegalovirus infection during pregnancy with maternofetal transmission induces
      a proinflammatory cytokine bias in placenta and amniotic fluid.
AB  - Congenital infection with cytomegalovirus (CMV) can induce immune responses and
      placental damage. By use of immunoassay panels, 27 cytokines were assessed in
      midtrimester amniotic fluid from 8 patients with congenital CMV, in midtrimester
      sera from 12 pregnant women with primary CMV infection, and in amniotic fluid and
      serum from uninfected maternal controls. Levels of the cytokines tumor necrosis
      factor alpha, interleukin 1beta, interleukin 12, and interleukin 17; the
      chemokines CCL2, CCL4, and CXCL10; and the growth factors granulocyte-macrophage
      colony-stimulating factor and platelet-derived growth factor bb were
      significantly elevated in amniotic fluid from congenital CMV patients (P < .01).
      Only CXCL10 was significantly higher in sera from CMV-infected pregnant women.
      CMV infection during pregnancy is associated with a shift in cytokine expression
      toward a proinflammatory state.

PMID- 22383679
TI  - EZH2 polymorphism and benefit from bevacizumab in colorectal cancer: another
      piece to the puzzle.

PMID- 22383680
TI  - Influence of zoledronic acid on disseminated tumor cells in primary breast cancer
      patients.
AB  - BACKGROUND: The presence of disseminated tumor cells (DTCs) in bone marrow of
      patients with early breast cancer (EBC) has been correlated with increased risk
      of metastatic disease or locoregional relapse. Zoledronic acid (ZOL) treatment
      has reduced DTCs in the bone marrow of patients with EBC in several studies. This
      controlled study sought to confirm these observations. PATIENTS AND METHODS:
      Patients with EBC and DTC-positive bone marrow were randomized (N = 96) to
      treatment with ZOL plus adjuvant systemic therapy or adjuvant systemic therapy
      alone. The change in DTC numbers at 12 months versus baseline was measured.
      RESULTS: DTC-positive patients treated with ZOL were more likely to become DTC
      negative after 12 months of treatment compared with the controls (67% versus 35%;
      P = 0.009). At 12 months, DTC counts decreased to a mean of 0.5 +/- 0.8 DTCs in
      the ZOL group and to 0.9 +/- 0.8 DTCs in the control group. In addition, ZOL was
      generally well tolerated. CONCLUSIONS: Treatment with ZOL improves elimination of
      DTCs. Further studies are needed to determine whether the reduction in DTCs by
      ZOL provides clinical benefit.

PMID- 22383681
TI  - Safe practices for compounding of parenteral nutrition.
AB  - Safe practices for sterile compounding are essential to preventing errors,
      particularly with parenteral nutrition (PN). This article reports several areas
      of errors in PN processes and provides recommendations for error prevention.

PMID- 22383682
TI  - Discussion session 1.

PMID- 22383683
TI  - Discussion session 2.

PMID- 22383684
TI  - Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase
      CGI-58.
AB  - We investigated here the specific role of CGI-58 in the regulation of energy
      metabolism in skeletal muscle. We first examined CGI-58 protein expression in
      various muscle types in mice, and next modulated CGI-58 expression during
      overexpression and knockdown studies in human primary myotubes and evaluated the
      consequences on oxidative metabolism. We observed a preferential expression of
      CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase
      activity. We next showed by pulse-chase that CGI-58 overexpression increased by
      more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG
      derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing
      reduced TAG hydrolysis and TAG-derived FA release and oxidation (-77%, P <
      0.001), whereas it increased glucose oxidation and glycogen synthesis.
      Interestingly, modulations of CGI-58 expression and FA release are reflected by
      changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation
      involves the activation of the peroxisome proliferator activating receptor-delta
      (PPARdelta) by lipolysis products. Altogether, these data reveal that CGI-58
      plays a limiting role in the control of oxidative metabolism by modulating FA
      availability and the expression of PPARdelta-target genes, and highlight an
      important metabolic function of CGI-58 in skeletal muscle.

PMID- 22383685
TI  - ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1
      mediated cholesterol efflux to plasma.
AB  - ApoE plays an important role in lipoprotein metabolism. This study investigated
      the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol
      metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice,
      AdhApoE3 resulted in decreased HDL cholesterol levels and a shift toward larger
      HDL in plasma, whereas hepatic cholesterol content increased (P < 0.05). These
      effects were dependent on scavenger receptor class B type I (SR-BI) as confirmed
      using SR-BI-deficient mice. Kinetic studies demonstrated increased plasma HDL
      cholesteryl ester catabolic rates (P < 0.05) and higher hepatic selective uptake
      of HDL cholesteryl esters in AdhApoE3-injected wild-type mice (P < 0.01).
      However, biliary and fecal sterol output as well as in vivo macrophage-to-feces
      RCT studied with (3)H-cholesterol-loaded mouse macrophage foam cells remained
      unchanged upon human apoE overexpression. Similar results were obtained using
      hApoE3 overexpression in human CETP transgenic mice. However, blocking ABCA1
      mediated cholesterol efflux from hepatocytes in AdhApoE3-injected mice using
      probucol increased biliary cholesterol secretion (P < 0.05), fecal neutral sterol
      excretion (P < 0.05), and in vivo RCT (P < 0.01), specifically within neutral
      sterols. These combined data demonstrate that systemic apoE overexpression
      increases i) SR-BI-mediated selective uptake into the liver and ii) ABCA1
      mediated efflux of RCT-relevant cholesterol from hepatocytes back to the plasma
      compartment, thereby resulting in unchanged fecal mass sterol excretion and
      overall in vivo RCT.

PMID- 22383687
TI  - On "Disability reconsidered: the paradox..." Roush SE, Sharby N. Phys Ther.
      2011;91:1715-1727.

PMID- 22383686
TI  - Genetic control of ATGL-mediated lipolysis modulates adipose triglyceride stores
      in leptin-deficient mice.
AB  - Dissecting the genetics of complex traits such as obesity allows the
      identification of causal genes for disease. Here, we show that the BALB/c mouse
      strain carries genetic variants that confer resistance to obesity induced by
      leptin-deficiency or a high-fat diet (HFD). We set out to identify the
      physiological and genetic bases underlying this phenotype. When compared with
      C57BL6/J ob/ob mice (B6), BALB/c ob/ob mice exhibited decreased food intake,
      increased thermogenic capacity, and improved fat catabolism, each of which can
      potentially modify obesity. Interestingly, analysis of F1 ob/ob (progeny of B6
      ob/+ * BALB/c ob+) mice revealed that obesity resistance in BALB/c ob/ob mice
      principally relied upon improved fat mobilization. This was mechanistically
      explained by increased adipose triglyceride lipase (ATGL) content in adipocytes,
      along with increased lipolysis and fatty acid oxidation. We conducted a genome
      wide scan and defined a quantitative trait locus (QTL) on chromosome 2. BALB/c
      alleles on chromosome 2 not only associated with the obesity resistance phenotype
      but also supported increased ATGL content in adipose tissue. In summary, our
      study provides evidence that leptin-independent control of adipocyte lipolysis
      rates directly modifies the balance of macronutrient handling and is sufficient
      to regulate fat mass in the absence of alterations in food intake and energy
      expenditure.-Marcelin, G., S-M. Liu, X. Li, G. J. Schwartz, and S. Chua.

PMID- 22383688
TI  - Is it beneficial to increase the provision of thrombolysis?-- a discrete-event
      simulation model.
AB  - BACKGROUND: Although Thrombolysis has been licensed in the UK since 2003, it is
      still administered only to a small percentage of eligible patients. AIM: We
      consider the impact of investing the impact of thrombolysis on important acute
      stroke services, and the effect on quality of life. The concept is illustrated
      using data from the Northern Ireland Stroke Service. DESIGN: Retrospective study.
      METHODS: We first present results of survival analysis utilizing length of stay
      (LOS) for discharge destinations, based on data from the Belfast City Hospital
      (BCH). None of these patients actually received thrombolysis but from those who
      would have been eligible, we created two initial groups, the first representing a
      scenario where they received thrombolysis and the second comprising those who do
      not receive thrombolysis. On the basis of the survival analysis, we created
      several subgroups based on discharge destination. We then developed a discrete
      event simulation (DES) model, where each group is a patient pathway within the
      simulation. Coxian phase type distributions were used to model the group LOS.
      Various scenarios were explored focusing on cost-effectiveness across hospital,
      community and social services had thrombolysis been administered to these
      patients, and the possible improvement in quality of life, should the proportion
      of patients who are administered thrombolysis be increased. Our aim in simulating
      various scenarios for this historical group of patients is to assess what the
      cost-effectiveness of thrombolysis would have been under different scenarios;
      from this we can infer the likely cost-effectiveness of future policies. RESULTS:
      The cost of thrombolysis is offset by reduction in hospital, community
      rehabilitation and institutional care costs, with a corresponding improvement in
      quality of life. CONCLUSION: Our model suggests that provision of thrombolysis
      would produce moderate overall improvement to the service assuming current levels
      of funding.

PMID- 22383689
TI  - Coronary artery mycotic aneurysm is the diagnostic challenge of the stent era.

PMID- 22383690
TI  - Effectiveness of statins in chronic kidney disease.
AB  - BACKGROUND: Previous studies show that statins reduce total cholesterol (TC)
      concentration by both 21% in primary prevention (PP) and secondary prevention
      (SP) in clinical trials and by ~24% in the general population. There are few data
      about the efficacy of statins on TC concentration and cardiovascular (CV) outcome
      in patients with chronic kidney disease (CKD). We evaluated the reduction of TC
      concentration and subsequent risk of CV morbidity and mortality with statins in
      CKD patients. METHODS: A population-based cohort study using a record-linkage
      database in Tayside, Scotland. A total of 2369 patients who had a primary
      diagnosis of CKD from Scottish Morbidity Record data or biochemistry database
      (serum creatinine of 220 MUmol/l or higher) and who had at least two separate TC
      measurements between 1993 and 2007 were studied. Patients were categorized into
      statin-exposed and statin-unexposed groups according to statin use status during
      the follow-up. They were also classified into PP (n = 1325) and SP (n = 1044)
      cohorts at the entry date. The main outcomes were TC concentration change from
      baseline, CV events [Antiplatelet Trialist's Collaboration (APTC)] and all-cause
      mortality during the follow-up. Cox regression models, in which statin use was a
      time-dependent variable, were employed to assess the risk of outcome and adjusted
      for other known confounders. RESULTS: Statin-associated TC concentrations
      decreased by 0.59 mmol/l (12%) in PP cohort and 0.56 mmol/l (13%) in SP cohort
      from 4.77 and 4.48 mmol/l at baselines, respectively. Statin use was associated
      with a reduced risk of APTC events, CV mortality or all-cause mortality in PP
      {adjusted hazard ratio (HR), 0.65 [95% confidence interval (CI) 0.48-0.88]; 0.73
      (95% CI 0.52-0.98); 0.59 (95% CI 0.48-0.73)} and SP [adjusted HR, 0.66 (95% CI
      0.52-0.84); 0.60 (95% CI 0.47-0.77); 0.56 (95% CI 0.47-0.68)], respectively.
      CONCLUSION: Statin use reduced TC concentrations by ~13% in patients with CKD.
      Statins were protective of APTC events, CV mortality and all-cause mortality in
      patients with or without established CV disease.

PMID- 22383691
TI  - Advances in the treatment of pancreatic neuroendocrine tumours.
AB  - Pancreatic neuroendocrine tumours (pNETs) are relatively rare and generally felt
      to follow an indolent course. But poorly differentiated tumours can behave
      aggressively with 5-year survival ranging from 31% to 48%. Recent data suggest
      that patients with pNETs may derive benefit from treatment targeting the
      molecular changes expressed in this tumour group. This article describes advances
      in the treatment of unresectable pNETs that have led to a doubling of progression
      free survival.

PMID- 22383693
TI  - Biomarkers predict progression of acute kidney injury after cardiac surgery.
AB  - Being able to predict whether AKI will progress could improve monitoring and
      care, guide patient counseling, and assist with enrollment into trials of AKI
      treatment. Using samples from the Translational Research Investigating Biomarker
      Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers
      measured at the time of first clinical diagnosis of early AKI after cardiac
      surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary
      albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase
      associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in
      380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary
      end point (progression of AKI defined by worsening AKIN stage) occurred in 45
      (11.8%) patients. Using multivariable logistic regression, we determined the risk
      of AKI progression. After adjustment for clinical predictors, compared with
      biomarker values in the lowest two quintiles, the highest quintiles of three
      biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95%
      confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3
      9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each
      biomarker improved risk classification compared with the clinical model alone,
      with plasma NGAL performing the best (category-free net reclassification
      improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of
      AKI diagnosis improve risk stratification and identify patients at higher risk
      for progression of AKI and worse patient outcomes.

PMID- 22383692
TI  - Identification of gene mutations in autosomal dominant polycystic kidney disease
      through targeted resequencing.
AB  - Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant
      polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1-32 as six
      pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the
      cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics
      of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2
      genes using next-generation sequencing by pooling long-range PCR amplicons and
      multiplexing bar-coded libraries. We used this approach to characterize a cohort
      of 230 patients with ADPKD. This process detected definitely and likely
      pathogenic variants in 115 (63%) of 183 patients with typical ADPKD. In addition,
      we identified atypical mutations, a gene conversion, and one missed mutation
      resulting from allele dropout, and we characterized the pattern of deep intronic
      variation for both genes. In summary, this strategy involving next-generation
      sequencing is a model for future genetic characterization of large ADPKD
      populations.

PMID- 22383694
TI  - The impact of renal function on outcomes of bariatric surgery.
AB  - The effect of CKD on the risks of bariatric surgery is not well understood. Using
      the American College of Surgeons National Surgical Quality Improvement Program
      Participant Use File, we analyzed 27,736 patients who underwent bariatric surgery
      from 2006 through 2008. Before surgery, 34 (0.12%) patients were undergoing long
      term dialysis. Among those not undergoing dialysis, 20,806 patients (75.0%) had a
      normal estimated GFR or stage 1 CKD, 5011 (18.07%) had stage 2 CKD, 1734 (6.25%)
      had stage 3 CKD, 94 (0.34%) had stage 4 CKD, and 91 (0.33%) had stage 5 CKD. In
      an unadjusted analysis, CKD stage was directly associated with complication rate,
      ranging from 4.6% for those with stage 1 CKD or normal estimated GFR to 9.9% for
      those with stage 5 CKD (test for trend, P<0.001). Multivariable logistic
      regression demonstrated that CKD stage predicts higher complication rates (odds
      ratio for each higher CKD stage, 1.30) after adjustment for diabetes and
      hypertension. Although patients with higher CKD stage had higher complication
      rates, the absolute incidence of complications remained <10%. In conclusion,
      these data demonstrate higher risks of bariatric surgery among patients with
      worse renal function, but whether the potential benefits outweigh the risks in
      this population requires further study.

PMID- 22383695
TI  - Pericyte TIMP3 and ADAMTS1 modulate vascular stability after kidney injury.
AB  - Kidney pericytes are progenitors of scar-forming interstitial myofibroblasts that
      appear after injury. The function of kidney pericytes as microvascular cells and
      how these cells detach from peritubular capillaries and migrate to the
      interstitial space, however, are poorly understood. Here, we used an unbiased
      approach to identify genes in kidney pericytes relevant to detachment and
      differentiation in response to injury in vivo, with a particular focus on genes
      regulating proteolytic activity and angiogenesis. Kidney pericytes rapidly
      activated expression of a disintegrin and metalloprotease with thrombospondin
      motifs-1 (ADAMTS1) and downregulated its inhibitor, tissue inhibitor of
      metalloproteinase 3 (TIMP3) in response to injury. Similarly to brain pericytes,
      kidney pericytes bound to and stabilized capillary tube networks in three
      dimensional gels and inhibited metalloproteolytic activity and angiogenic
      signaling in endothelial cells. In contrast, myofibroblasts did not have these
      vascular stabilizing functions despite their derivation from kidney pericytes.
      Pericyte-derived TIMP3 stabilized and ADAMTS1 destabilized the capillary tubular
      networks. Furthermore, mice deficient in Timp3 had a spontaneous microvascular
      phenotype in the kidney resulting from overactivated pericytes and were more
      susceptible to injury-stimulated microvascular rarefaction with an exuberant
      fibrotic response. Taken together, these data support functions for kidney
      pericytes in microvascular stability, highlight central roles for regulators of
      extracellular proteolytic activity in capillary homoeostasis, and identify
      ADAMTS1 as a marker of activation of kidney pericytes.

PMID- 22383696
TI  - Cardiovascular disease in children with chronic kidney disease.
AB  - More than a decade ago, cardiovascular disease (CVD) was recognized as a major
      cause of death in children with advanced CKD. This observation has sparked the
      publication of multiple studies assessing cardiovascular risk, mechanisms of
      disease, and early markers of CVD in this population. Similar to adults, children
      with CKD have an extremely high prevalence of traditional and uremia-related CVD
      risk factors. Early markers of cardiomyopathy, such as left ventricular
      hypertrophy and dysfunction, and early markers of atherosclerosis, such as
      increased carotid artery intima-media thickness, carotid arterial wall stiffness,
      and coronary artery calcification, are frequently present in these children,
      especially those on maintenance dialysis. As a population without preexisting
      symptomatic cardiac disease, children with CKD potentially receive significant
      benefit from aggressive attempts to prevent and treat CVD. Early CKD, before
      needing dialysis, is the optimal time to both identify modifiable risk factors
      and intervene in an effort to avert future CVD. Slowing the progression of CKD,
      avoiding long-term dialysis and, if possible, conducting preemptive
      transplantation may represent the best strategies to decrease the risk of
      premature cardiac disease and death in children with CKD.

PMID- 22383697
TI  - Biphasic time course of the changes in aldosterone biosynthesis under high-salt
      conditions in Dahl salt-sensitive rats.
AB  - OBJECTIVE: The comorbidity of excess salt and elevated plasma aldosterone has
      deleterious effects in cardiovascular disease. We evaluated the mechanisms behind
      the paradoxical increase in aldosterone biosynthesis in relation to dietary
      intake of salt. METHODS AND RESULTS: Dahl salt-sensitive (Dahl-S) and salt
      resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels
      of aldosterone in the adrenal gland and heart were quantified by liquid
      chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats,
      we found that the delayed and paradoxical increase in aldosterone biosynthesis
      after the initial and appropriate response to high salt. The late rise in
      aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in
      the zona glomerulosa and increased adrenal angiotensin II levels and renin
      angiotensin system components. It preceded the appearance of left ventricular
      systolic dysfunction and renal insufficiency. Blockade of angiotensin AT(1)
      receptors reversed the paradoxical increase in aldosterone biosynthesis. In
      contrast, Dahl-R rats maintained the initial suppression of aldosterone
      biosynthesis. Aldosterone levels in the heart closely paralleled those in the
      plasma and adrenal gland and disappeared after bilateral adrenalectomy.
      CONCLUSIONS: Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone
      production via activation of the local renin-angiotensin system in the adrenal
      gland, thereby creating the comorbidity of excess salt and elevated plasma
      aldosterone.

PMID- 22383698
TI  - Hepcidin destabilizes atherosclerotic plaque via overactivating macrophages after
      erythrophagocytosis.
AB  - OBJECTIVE: To explore a direct and causal relationship between vascular hepcidin
      and atherosclerotic plaque stability. METHODS AND RESULTS: Accelerated
      atherosclerotic lesions were established by perivascular collar placement in
      apolipoprotein E-deficient (ApoE(-/-)) mice. Adenoviral overexpression of
      hepcidin in the carotid artery during plaque formation enhanced intraplaque
      macrophage infiltration and suppressed the contents of collagen and vascular
      smooth muscle cells, whereas hepcidin shRNA treatment exerts opposite effects.
      The overexpression or knockdown of hepcidin did not affect plaque lipid
      deposition but increased or decreased oxidized low-density lipoprotein (ox-LDL)
      levels within intraplaque macrophages. In cultured macrophages, ox-LDL not only
      increased reactive oxygen species formation, inflammatory cytokine production,
      and apoptosis but also upregulated hepcidin expression. However, hepcidin did not
      exaggerate the ox-LDL-induced activation of macrophages until an onset of
      erythrophagocytosis. Whereas hepcidin was critical for the upregulation of L
      ferritin and H-ferritin in both ox-LDL-treated erythrophagocytosed macrophages
      and atherosclerotic plaques, the adding of iron chelators suppressed the
      intracellular lipid accumulation, reactive oxygen species formation, inflammatory
      cytokine expression, and apoptosis in erythrophagocytosed macrophages.
      CONCLUSIONS: Hepcidin promotes plaque destabilization partly by exaggerating
      inflammatory cytokine release, intracellular lipid accumulation, oxidative
      stress, and apoptosis in the macrophages with iron retention.

PMID- 22383699
TI  - Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion
      flux independent mechanism.
AB  - OBJECTIVE: Phenotypic modulation of vascular smooth muscle cells has been
      associated with a decreased expression of all voltage-dependent potassium channel
      (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact,
      upregulation of Kv1.3 currents seems to be important to modulate proliferation of
      mice femoral vascular smooth muscle cells in culture. This study was designed to
      explore if these changes in Kv1 expression pattern constituted a landmark of
      phenotypic modulation across vascular beds and to investigate the mechanisms
      involved in the proproliferative function of Kv1.3 channels. METHODS AND RESULTS:
      Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and
      aortic vascular smooth muscle cells, and their correlate with protein expression
      was electrophysiologicaly confirmed using selective blockers. Heterologous
      expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the
      proliferation rate. The proproliferative effect of Kv1.3 channels was reproduced
      by "poreless" mutants but disappeared when voltage-dependence of gating was
      suppressed. CONCLUSIONS: These findings suggest that the signaling cascade
      linking Kv1.3 functional expression to cell proliferation is activated by the
      voltage-dependent conformational change of the channels without needing ion
      conduction. Additionally, the conserved upregulation of Kv1.3 on phenotypic
      modulation in several vascular beds makes this channel a good target to control
      unwanted vascular remodeling.

PMID- 22383701
TI  - Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and
      vascular recruitment during hyperlipidemia.
AB  - OBJECTIVE: The chemokine receptor CX(3)CR1 is an inflammatory mediator in
      vascular diseases. On platelets, its ligation with fractalkine (CX(3)CL1) induces
      platelet activation followed by leukocyte recruitment to activated endothelium.
      Here, we evaluated the expression and role of platelet-CX(3)CR1 during
      hyperlipidemia and vascular injury. METHODS AND RESULTS: The existence of
      CX(3)CR1 on platelets at mRNA and protein level was analyzed by RT-PCR,
      quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX(3)CR1
      expression was detected on human platelets after activation and, along with
      increased binding of CX(3)CL1, platelet CX(3)CR1 was also involved in the
      formation of platelet-monocyte complexes. Interestingly, the expression of
      CX(3)CR1 was elevated on platelets from hyperlipidemic mice. Accordingly,
      CX(3)CL1-binding and the number of circulating platelet-monocyte complexes were
      increased. In addition, CX(3)CR1 supported monocyte arrest on inflamed smooth
      muscle cells in vitro, whereas CX(3)CR1-deficient platelets showed decreased
      adhesion to the denuded vessel wall in vivo. CONCLUSIONS: Platelets in
      hyperlipidemic mice display increased CX(3)CR1-expression and assemble with
      circulating monocytes. The formation of platelet-monocyte complexes and the
      detection of platelet-bound CX(3)CL1 on inflamed smooth muscle cells suggest a
      significant involvement of the CX(3)CL1-CX(3)CR1 axis in platelet accumulation
      and monocyte recruitment at sites of arterial injury in atherosclerosis.

PMID- 22383700
TI  - Animal models of atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disorder that is the underlying cause
      of most cardiovascular disease. Both cells of the vessel wall and cells of the
      immune system participate in atherogenesis. This process is heavily influenced by
      plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the
      artery. A variety of small and large animal models have been used to study the
      atherogenic process. No model is ideal as each has its own advantages and
      limitations with respect to manipulation of the atherogenic process and modeling
      human atherosclerosis or lipoprotein profile. Useful large animal models include
      pigs, rabbits, and nonhuman primates. Due in large part to the relative ease of
      genetic manipulation and the relatively short time frame for the development of
      atherosclerosis, murine models are currently the most extensively used. Although
      not all aspects of murine atherosclerosis are identical to humans, studies using
      murine models have suggested potential biological processes and interactions that
      underlie this process. As it becomes clear that different factors may influence
      different stages of lesion development, the use of mouse models with the ability
      to turn on or delete proteins or cells in tissue specific and temporal manner
      will be very valuable.

PMID- 22383702
TI  - Transition from obesity to metabolic syndrome is associated with altered
      myocardial autophagy and apoptosis.
AB  - OBJECTIVE: Transition from obesity to metabolic-syndrome (MetS) promotes
      cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms
      are incompletely understood. We tested the hypothesis that development of insulin
      resistance and MetS is associated with impaired myocardial cellular turnover.
      METHODS AND RESULTS: MetS-prone Ossabaw pigs were randomized to 10 weeks of
      standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6
      each). Cardiac structure, function, and myocardial oxygenation were assessed by
      multidetector computed-tomography and Blood Oxygen Level-Dependent-MRI, the
      microcirculation with microcomputed-tomography, and injury mechanisms by
      immunoblotting and histology. Both obese and MetS showed obesity and
      dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and
      myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent-MRI
      showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and
      fibrosis also increased in both obese and MetS, but more pronouncedly in MetS.
      Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis.
      CONCLUSIONS: Development of insulin resistance characterizing a transition from
      obesity to MetS is associated with progressive changes of myocardial autophagy,
      apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring
      myocardial cellular turnover may represent a novel therapeutic target for
      preserving myocardial structure and function in obesity and MetS.

PMID- 22383704
TI  - Bcl-x inactivation in macrophages accelerates progression of advanced
      atherosclerotic lesions in Apoe(-/-) mice.
AB  - OBJECTIVE: Bcl-x is the most abundantly expressed member of the Bcl-2 gene family
      in macrophages, but its role in macrophage apoptosis during atherogenesis is
      unknown. METHODS AND RESULTS: We previously reported dual pro- and
      antiatherogenic effects of macrophage survival in early versus advanced
      atherosclerotic lesions, respectively, potentially reflecting growing impairment
      of efferocytosis during plaque progression. Here, we specifically inactivated Bcl
      x in macrophages and evaluated its impact on atherosclerotic lesion formation in
      Apoe(-/-) mice at various stages of the disease. Bcl-x deficiency in macrophages
      increased their susceptibility to apoptosis, resulting in the depletion of tissue
      macrophages in vivo, including its major pool, Kuppfer cells in the liver. We
      also observed increased cholesterol levels that were, however, not associated
      with any acceleration of early atherosclerotic plaque progression. This
      observation suggests that the atheroprotective effect of macrophage apoptosis at
      that stage of disease was counterbalanced by enhanced cholesterol levels. Bcl-x
      KO(mac)/Apoe(-/-) mice exhibited significantly larger advanced lesions than
      control mice. These lesions showed vulnerable traits. Such enhanced lesion size
      may occur as a result not only of apoptotic cell accumulation but also of
      elevated cholesterol levels. CONCLUSIONS: Modulation of macrophage resistance to
      apoptosis through targeted deletion of Bcl-x has a major impact on the entire
      macrophage cell population in the body, including Kupffer cells. Macrophage
      survival may, therefore, not only influence atherosclerotic plaque development
      and vulnerability but also cholesterol metabolism.

PMID- 22383703
TI  - Targeted focal adhesion kinase activation in cardiomyocytes protects the heart
      from ischemia/reperfusion injury.
AB  - OBJECTIVE: We previously reported that cardiac-restricted deletion of focal
      adhesion kinase (FAK) exacerbated myocyte death following ischemia/reperfusion
      (I/R). Here, we interrogated whether targeted elevation of myocardial FAK
      activity could protect the heart from I/R injury. METHODS AND RESULTS: Transgenic
      mice were generated with myocyte-specific expression of a FAK variant (termed
      SuperFAK) that conferred elevated allosteric activation. FAK activity in
      unstressed transgenic hearts was modestly elevated, but this had no discernable
      effect on anabolic heart growth or cardiac function. Importantly, SuperFAK hearts
      exhibited a dramatic increase in FAK activity and a reduction in myocyte
      apoptosis and infarct size 24 to 72 hours following I/R. Moreover, serial
      echocardiography revealed that the transgenic mice were protected from cardiac
      decompensation for up to 8 weeks following surgery. Mechanistic studies revealed
      that elevated FAK activity protected cardiomyocytes from I/R-induced apoptosis by
      enhancing nuclear factor-kappaB (NF-kappaB)-dependent survival signaling during
      the early period of reperfusion (30 and 60 minutes). Moreover, adenoviral
      mediated expression of SuperFAK in cultured cardiomyocytes attenuated H(2)O(2) or
      hypoxia/reoxygenation-induced apoptosis, whereas blockade of the NF-kappaB
      pathway using a pharmacological inhibitor or small interfering RNAs completely
      abolished the beneficial effect of SuperFAK. CONCLUSIONS: Enhancing cardiac FAK
      activity attenuates I/R-induced myocyte apoptosis through activation of the
      prosurvival NF-kappaB pathway and may represent a novel therapeutic strategy for
      ischemic heart diseases.

PMID- 22383706
TI  - Endocrine nitric oxide bioactivity and hypoxic vasodilation by inhaled nitric
      oxide.

PMID- 22383705
TI  - A novel mRNA binding protein complex promotes localized plasminogen activator
      inhibitor-1 accumulation at the myoendothelial junction.
AB  - OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) has previously been shown to
      be key to the formation of myoendothelial junctions (MEJs) in normal and
      pathological states (eg, obesity). We therefore sought to identify the mechanism
      whereby PAI-1 could be selectively accumulated at the MEJ. METHODS AND RESULTS:
      We identified PAI-1 protein enrichment at the MEJ in obese mice and in response
      to tumor necrosis factor (TNF-alpha) with a vascular cell coculture. However, PAI
      1 mRNA was also found at the MEJ and transfection with a PAI-1-GFP with TNF-alpha
      did not demonstrate trafficking of the protein to the MEJ. We therefore
      hypothesized the PAI-1 mRNA was being locally translated and identified serpine
      binding protein-1, which stabilizes PAI-1 mRNA, as being enriched in obese mice
      and after treatment with TNF-alpha, whereas Staufen, which degrades PAI-1 mRNA,
      was absent in obese mice and after TNF-alpha application. We identified
      nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding
      partner with a functional tau-like microtubule binding domain. Application of
      peptides against the microtubule binding domain significantly decreased the
      number of MEJs and the amount of PAI-1 at the MEJ. CONCLUSIONS: We conclude that
      PAI-1 can be locally translated at the MEJ as a result of a unique mRNA binding
      protein complex.

PMID- 22383707
TI  - Novel communication between myocyte lipid storage and fat burning unveiled.

PMID- 22383708
TI  - Minimal and null predictive effects for the most popular blood biomarkers of
      cardiovascular disease.

PMID- 22383709
TI  - Interplay between heart and skeletal muscle disease in heart failure: the 2011
      George E. Brown Memorial Lecture.
AB  - The study of single gene disorders often provides insight for more complex human
      disease. Mutations in the genes encoding the dystrophin protein complex cause
      muscular dystrophy and cardiomyopathy by destabilizing the plasma membrane of
      skeletal myofibers and cardiomyocytes. In these diseases, progressive skeletal
      muscle degeneration and weakness contribute to cardiac dysfunction. Moreover, the
      pace and pattern of muscle weakness, along with onset of cardiomyopathy, is
      highly variable even when associated with the same identical mutation. Using a
      mouse model of muscular dystrophy and cardiomyopathy, we identified genetic loci
      that modify muscle pathology and cardiac fibrosis. Distinct genetic modifiers
      were identified for diaphragm and abdominal musculature, and these genetic
      intervals differ from those that regulate pathology in the skeletal muscle of the
      limbs and the heart. One modifier gene was identified and highlights the
      importance of the transforming growth factor-beta pathway in the pathogenesis of
      muscular dystrophy and cardiomyopathy. We determined that canonical transforming
      growth factor-beta signaling contributes to heart and muscle dysfunction using a
      Drosophila model. Together, these studies demonstrate the value of using a
      genetically sensitized model to uncover pathways that regulate heart failure and
      muscle weakness.

PMID- 22383710
TI  - Decoding the cardiac message: the 2011 Thomas W. Smith Memorial Lecture.
AB  - This review reflects and expands on the contents of my presentation at the Thomas
      W. Smith Memorial Lecture at American Heart Association Scientific Sessions,
      2011. "Decoding the cardiac message" refers to accumulating results from ongoing
      microRNA research that is altering longstanding concepts of the mechanisms for,
      and consequences of, messenger RNA (mRNA) regulation in the heart. First, I
      provide a brief historical perspective of the field of molecular genetics,
      touching on seminal research that paved the way for modern molecular
      cardiovascular research and helped establish the foundation for current concepts
      of mRNA regulation in the heart. I follow with some interesting details about the
      specific research that led to the discovery and appreciation of microRNAs as
      highly conserved pivotal regulators of RNA expression and translation. Finally, I
      provide a personal viewpoint as to how agnostic genome-wide techniques for
      measuring microRNAs, their mRNA targets, and their protein products can be
      applied in an integrated multisystems approach to uncover direct and indirect
      effects of microRNAs. Experimental designs integrating next-generation sequencing
      and global proteomics have the potential to address unanswered questions
      regarding microRNA-mRNA interactions in cardiac disease, how disease alters mRNA
      targeting by specific microRNAs, and how mutational and polymorphic nucleotide
      variation in microRNAs can affect end-organ function and stress response.

PMID- 22383713
TI  - Remote ischemic preconditioning is redundant in patients undergoing coronary
      artery bypass graft surgery who are already protected by volatile anesthetics.

PMID- 22383714
TI  - Pregnancy development from day 28 to 42 of gestation in postpartum Holstein cows
      that were either milked (lactating) or not milked (not lactating) after calving.
AB  - The objective was to determine if lactation affects fetal and placental
      development from day 28 to 42 of gestation. Bos taurus Holstein cows were
      assigned to one of the two treatments immediately after parturition (lactating
      (n=23) or nonlactating (dried off immediately after calving; n=20)). Cows were
      inseminated at ~60 days postpartum with semen from a single ejaculate. Pregnant
      cows were slaughtered at 1 of 3 days of gestation (day 28, 35, or 42) and tissues
      were collected. The interval to first insemination, services per conception, and
      days to pregnancy were similar for lactating and nonlactating cows. Lactating
      cows had greater plasma GH and nonesterified fatty acids. Nonlactating cows had
      greater plasma glucose, insulin, and IGF1. There was no effect of lactation on
      plasma progesterone or estradiol concentrations. Lactation had a negative effect
      on the weight of the fetus and placenta (weights were less in lactating cows).
      Fetuses collected from cows that became pregnant after first insemination were
      heavier than fetuses collected from cows that became pregnant after second or
      third insemination. Pregnancy after first insemination was associated with
      greater blood glucose and IGF1 during the first 30 days postpartum. The
      conclusions were that lactation negatively affects the growth of fetal and
      placental tissues perhaps through a mechanism that involves hormones and
      metabolites that are affected by lactation. Fetal growth within cows conceiving
      at first insemination compared to second or third insemination was more rapid and
      was associated with greater blood glucose and IGF1 early postpartum (before day
      30).

PMID- 22383712
TI  - Gene therapy for heart failure.
AB  - Congestive heart failure accounts for half a million deaths per year in the
      United States. Despite its place among the leading causes of morbidity,
      pharmacological and mechanic remedies have only been able to slow the progression
      of the disease. Today's science has yet to provide a cure, and there are few
      therapeutic modalities available for patients with advanced heart failure. There
      is a critical need to explore new therapeutic approaches in heart failure, and
      gene therapy has emerged as a viable alternative. Recent advances in
      understanding of the molecular basis of myocardial dysfunction, together with the
      evolution of increasingly efficient gene transfer technology, have placed heart
      failure within reach of gene-based therapy. The recent successful and safe
      completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase
      pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new
      era for gene therapy for the treatment of heart failure.

PMID- 22383715
TI  - Brucella peritonitis in peritoneal dialysis: a case report and review of the
      literature.
AB  - Brucellosis is a zoonotic infection that humans contract usually by ingestion of
      unpasteurized milk and milk products or by direct contact with raw infected
      animal products. Infection is endemic in many countries, including Turkey. Being
      a systemic disease, brucellosis may affect almost any part of the body. The
      peritoneum is a site rarely involved in brucellosis. Most peritonitis episodes
      involving Brucella species have been spontaneous cases reported in cirrhotic
      patients with ascites. To our knowledge, the literature contains only 5 cases of
      Brucella peritonitis related to continuous ambulatory peritoneal dialysis. Here,
      we report Brucella peritonitis in a continuous ambulatory peritoneal dialysis
      patient, and we discuss the relevant literature.

PMID- 22383711
TI  - Dietary fat and heart failure: moving from lipotoxicity to lipoprotection.
AB  - There is growing evidence suggesting that dietary fat intake affects the
      development and progression of heart failure. Studies in rodents show that in the
      absence of obesity, replacing refined carbohydrate with fat can attenuate or
      prevent ventricular expansion and contractile dysfunction in response to
      hypertension, infarction, or genetic cardiomyopathy. Relatively low intake of n-3
      polyunsaturated fatty acids from marine sources alters cardiac membrane
      phospholipid fatty acid composition, decreases the onset of new heart failure,
      and slows the progression of established heart failure. This effect is associated
      with decreased inflammation and improved resistance to mitochondrial permeability
      transition. High intake of saturated, monounsaturated, or n-6 polyunsaturated
      fatty acids has also shown beneficial effects in rodent studies. The underlying
      mechanisms are complex, and a more thorough understanding is needed of the
      effects on cardiac phospholipids, lipid metabolites, and metabolic flux in the
      normal and failing heart. In summary, manipulation of dietary fat intake shows
      promise in the prevention and treatment of heart failure. Clinical studies
      generally support high intake of n-3 polyunsaturated fatty acids from marine
      sources to prevent and treat heart failure. Additional clinical and animals
      studies are needed to determine the optimal diet in terms of saturated,
      monounsaturated, and n-6 polyunsaturated fatty acids intake for this vulnerable
      patient population.

PMID- 22383716
TI  - Peritoneal dialysis after cardiothoracic surgery: do it!

PMID- 22383718
TI  - Use of a peritoneal dialysis remote monitoring system in India.

PMID- 22383717
TI  - Intermittent peritoneal dialysis: just enough for some or inadequate altogether?

PMID- 22383719
TI  - Sterile peritonitis with high-dose amino acid-containing peritoneal dialysis
      solution in children.

PMID- 22383720
TI  - Severe hyperkalemia in a peritoneal dialysis patient after consumption of salt
      substitute.

PMID- 22383721
TI  - Cinacalcet improves control of secondary hyperparathyroidism in peritoneal
      dialysis: a multicenter study.

PMID- 22383722
TI  - Free water transport measured by double mini-PET may be increased by higher
      glucose exposure in peritoneal dialysis.

PMID- 22383723
TI  - Treatment by functional electrical therapy of an unresolved peritoneal leakage in
      a peritoneal dialysis patient.

PMID- 22383724
TI  - Peritoneal dialysis catheter malfunction because of encasement by an extraluminal
      fibrin sheath.

PMID- 22383725
TI  - Chemical peritonitis after intraperitoneal sodium thiosulfate.

PMID- 22383726
TI  - The peritoneal equilibration test should be included in routine monitoring of
      peritoneal dialysis patients.

PMID- 22383728
TI  - First report of peritoneal dialysis-related peritonitis caused by Citrobacter
      amalonaticus.

PMID- 22383729
TI  - Mycobacterium mucogenicum peritonitis in a continuous ambulatory peritoneal
      dialysis patient.

PMID- 22383730
TI  - Early surgical intervention may prevent peritonitis in cases with Tenckhoff
      catheter infection by nontuberculous mycobacterium.

PMID- 22383731
TI  - A case report of expanded-spectrum beta-lactamase-producing Klebsiella pneumoniae
      peritonitis in a patient on continuous ambulatory peritoneal dialysis.

PMID- 22383732
TI  - Dialysis modality for patients with Turner syndrome and renal failure.

PMID- 22383733
TI  - Gluten-related recurrent peripheral facial palsy.

PMID- 22383734
TI  - Systematic assessment of apraxia and functional predictions from the Birmingham
      Cognitive Screen.
AB  - OBJECTIVE: The validity and functional predictive values of the apraxia tests in
      the Birmingham Cognitive Screen (BCoS) were evaluated. BCoS was developed to
      identify patients with different forms of praxic deficit using procedures
      designed to be inclusive for patients with aphasia and/or spatial neglect.
      METHOD: Observational studies were conducted from a university neuropsychological
      assessment centre and from acute and rehabilitation stroke care hospitals
      throughout an English region. Volunteers from referred patients with chronic
      acquired brain injuries, a consecutive hospital sample of patients within 3
      months of stroke (n=635) and a population based healthy control sample (n=100)
      were recruited. The main outcome measures used were the Barthel Index, the
      Nottingham Extended Activities of Daily Living Scale as well as recovery from
      apraxia. RESULTS: There were high inter-rater reliabilities and correlations
      between the BCoS apraxia tasks and counterpart tests from the literature. The
      vast majority (88.3%) of the stroke survivors were able to complete the screen.
      Pantomime and gesture recognition tasks were more sensitive in differentiating
      between individuals with left hemisphere damage and right hemisphere damage
      whereas the Multistep Object Use test and the imitation task had higher
      functional correlates over and above effects of hemiplegia. Together, the initial
      scores of the four tasks enabled predictions with 75% accuracy, the recovery of
      apraxia and independence level at 9 months. CONCLUSIONS: As a model based
      assessment, BCoS offers a quick and valid way to detect apraxia and predict
      functional recovery. It enables early and informative assessment of most stroke
      patients for rehabilitation planning.

PMID- 22383735
TI  - GENI-DB: a database of global events for epidemic intelligence.
AB  - We present a novel public health database (GENI-DB) in which news events on the
      topic of over 176 infectious diseases and chemicals affecting human and animal
      health are compiled from surveillance of the global online news media in 10
      languages. News event frequency data were gathered systematically through the
      BioCaster public health surveillance system from July 2009 to the present and is
      available to download by the research community for purposes of analyzing trends
      in the global burden of infectious diseases. Database search can be conducted by
      year, country, disease and language. AVAILABILITY: The GENI-DB is freely
      available via a web portal at http://born.nii.ac.jp/.

PMID- 22383737
TI  - The gender(s) in the room.

PMID- 22383736
TI  - Early immunologic correlates of HIV protection can be identified from
      computational analysis of complex multivariate T-cell flow cytometry assays.
AB  - MOTIVATION: Polychromatic flow cytometry (PFC), has enormous power as a tool to
      dissect complex immune responses (such as those observed in HIV disease) at a
      single cell level. However, analysis tools are severely lacking. Although high
      throughput systems allow rapid data collection from large cohorts, manual data
      analysis can take months. Moreover, identification of cell populations can be
      subjective and analysts rarely examine the entirety of the multidimensional
      dataset (focusing instead on a limited number of subsets, the biology of which
      has usually already been well-described). Thus, the value of PFC as a discovery
      tool is largely wasted. RESULTS: To address this problem, we developed a
      computational approach that automatically reveals all possible cell subsets. From
      tens of thousands of subsets, those that correlate strongly with clinical outcome
      are selected and grouped. Within each group, markers that have minimal relevance
      to the biological outcome are removed, thereby distilling the complex dataset
      into the simplest, most clinically relevant subsets. This allows complex
      information from PFC studies to be translated into clinical or resource-poor
      settings, where multiparametric analysis is less feasible. We demonstrate the
      utility of this approach in a large (n=466), retrospective, 14-parameter PFC
      study of early HIV infection, where we identify three T-cell subsets that
      strongly predict progression to AIDS (only one of which was identified by an
      initial manual analysis). AVAILABILITY: The 'flowType: Phenotyping Multivariate
      PFC Assays' package is available through Bioconductor. Additional documentation
      and examples are available at: www.terryfoxlab.ca/flowsite/flowType/
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online. CONTACT: rbrinkman@bccrc.ca.

PMID- 22383738
TI  - Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in
      NOD/SCID/Il2rg-/- mice.
AB  - PURPOSE: Acute myeloid leukemia (AML) accounts for more than half of fatal cases
      in all pediatric leukemia patients; this observation highlights the need of more
      effective therapies. Thus, we investigated whether interleukin (IL)-27, an
      immunomodulatory cytokine, functions as an antitumor agent against pediatric AML
      cells. EXPERIMENTAL DESIGN: Expression of WSX-1 and gp130 on AML cells from 16
      pediatric patients was studied by flow cytometry. Modulation of leukemia cell
      proliferation or apoptosis upon IL-27 treatment in vitro was tested by
      bromodeoxyuridine/propidium iodide (PI) and Ki67, or Annexin V/PI staining and
      flow cytometric analysis. The angiogenic potential of AML cells treated or not
      with IL-27 was studied by chorioallantoic membrane assay and PCR array. In vivo
      studies were carried out using nonobese diabetic/severe combined immunodeficient
      (NOD/SCID)/Il2rg(-/-) mice injected intravenously with five pediatric AML cell
      samples. Leukemic cells engrafted in PBS and IL-27-treated animals were studied
      by immunohistochemical/morphologic analysis and by PCR array for expression
      angiogenic/dissemination-related genes. RESULTS: We provided the first
      demonstration that (i) AML cells injected into NOD/SCID/Il2rg(-/-) mice gave rise
      to leukemia dissemination that was severely hampered by IL-27, (ii) compared with
      controls, leukemia cells harvested from IL-27-treated mice showed significant
      reduction of their angiogenic and spreading related genes, and (iii) similarly to
      what was observed in vivo, IL-27 reduced in vitro AML cell proliferation and
      modulated the expression of different genes involved in the angiogenic/spreading
      process. CONCLUSION: These results provide an experimental rationale for the
      development of future clinical trials aimed at evaluating the toxicity and
      efficacy of IL-27.

PMID- 22383740
TI  - Genetic and epigenetic studies offer new therapeutic options for the treatment of
      T-cell acute lymphoblastic leukemia.

PMID- 22383739
TI  - Prognostic and predictive significance of plasma HGF and IL-8 in a phase III
      trial of chemoradiation with or without tirapazamine in locoregionally advanced
      head and neck cancer.
AB  - PURPOSE: Hepatocyte growth factor (HGF) is a hypoxia-induced secreted protein
      that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the
      role of circulating HGF and IL-8 as prognostic and predictive factors for
      efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin. EXPERIMENTAL DESIGN:
      Patients with stages III to IV head and neck cancer were randomized to receive
      radiotherapy with cisplatin (CIS) or CIS plus TPZ (TPZ/CIS). Eligibility for the
      substudy included plasma sample availability for HGF and IL-8 assay by ELISA and
      no major radiation deviations (N = 498). Analyses included adjustment for major
      prognostic factors. p16(INK4A) staining (human papillomavirus surrogate) was
      carried out on available tumors. Thirty-nine patients had hypoxia imaging with
      (18)F-fluoroazomycin arabinoside ((18)FAZA)-positron emission tomography.
      RESULTS: Elevated IL-8 level was associated with worse overall survival (OS)
      irrespective of treatment. There was an interaction between HGF and treatment arm
      (P = 0.053); elevated HGF was associated with worse OS in the control but not in
      the TPZ/CIS arm. Similar trends were observed in analyses restricted to
      p16(INK4A)-negative patients. Four subgroups defined by high and low HGF/IL-8
      levels were examined for TPZ effect; the test for interaction with arm was P =
      0.099. TPZ/CIS seemed to be beneficial for patients with high HGF and IL-8 but
      adverse for low HGF and high IL-8. Only HGF correlated with (18)FAZA tumor
      standard uptake value. CONCLUSIONS: IL-8 is an independent prognostic factor
      irrespective of treatment. There is an interaction between HGF and treatment arm.
      Certain subgroups based on IL-8/HGF levels seemed to do better with TPZ/CIS while
      others did worse, highlighting the complexity of hypoxia targeting in unselected
      patients.

PMID- 22383741
TI  - DNMT3A and stem cell function: new insights into old pathways.

PMID- 22383742
TI  - The role of antifungal treatment in hematology.

PMID- 22383743
TI  - Activation of the NOTCH1 pathway in chronic lymphocytic leukemia.

PMID- 22383744
TI  - European Bone Marrow Working Group trial on reproducibility of World Health
      Organization criteria to discriminate essential thrombocythemia from prefibrotic
      primary myelofibrosis. Haematologica 2012;97(3):360-5--comment.

PMID- 22383746
TI  - Daily variability in mineral metabolites in CKD and effects of dietary calcium
      and calcitriol.
AB  - BACKGROUND AND OBJECTIVES: Primary prevention of disordered mineral metabolism in
      CKD necessitates knowledge of its early pathophysiology. This study evaluated
      daily fluctuations in mineral metabolites in patients with CKD stages 3 and 4
      before and after short-term calcitriol treatment and tested the effects of
      dietary calcium and calcitriol supplementation on these parameters in the dynamic
      postprandial setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twelve CKD
      patients received calcitriol (0.25 MUg daily for 1 week) with hourly assessments
      of mineral metabolites made throughout the day and in the context of standardized
      meals before and after treatment. Calcium content (250 versus 500 mg) in the
      breakfasts constituted the dietary calcium intervention. Twelve healthy
      volunteers were used as controls. RESULTS: At baseline, compared with controls,
      fasting CKD subjects had higher parathyroid hormone and fibroblast growth factor
      23 levels and greater fractional excretion of phosphate. After breakfast, urinary
      calcium excretion increased and parathyroid hormone levels dipped transiently in
      both groups, but they rose soon thereafter, reaching higher peaks in CKD.
      Calcitriol decreased fasting parathyroid hormone levels, and when combined with
      dietary calcium load, it normalized the postprandial parathyroid and calcemic
      responses. Daily variability in mineral metabolites was preserved in CKD before
      and after calcitriol. Fibroblast growth factor 23 levels increased after
      calcitriol, although the response was heterogeneous. CONCLUSIONS: Short-term
      treatment with calcitriol and dietary calcium supplementation normalizes the
      parathyroid and calcemic postprandial responses in patients with CKD, in whom the
      diurnal rhythms of mineral metabolites are preserved. Future studies should
      investigate the variable fibroblast growth factor 23 response to calcitriol in
      CKD.

PMID- 22383747
TI  - FGF23, albuminuria, and disease progression in patients with chronic IgA
      nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Fibroblast growth factor-23 (FGF23) regulates mineral
      metabolism. Circulatory FGF23 levels are increased and predict outcomes in CKD.
      However, the relation of FGF23 to albuminuria and disease progression in patients
      with CKD and one underlying diagnosis is unknown. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: Prospective, observational study in 180 patients with IgA
      nephropathy (IgAN), CKD stage 1-4, and median 55-month follow-up (range, 12-177
      months). Primary outcomes were (1) time-averaged albuminuria, (2A) progression to
      CKD stage 5 or >=50% loss of estimated GFR, (2B) progression to CKD stage 5 or
      >=25% loss of estimated GFR within 10 years, and (3) annual loss of estimated
      GFR. RESULTS: FGF23 was independently associated with baseline and time-averaged
      albuminuria (change in 1 g/24 hour albuminuria per increase in log FGF23: beta =
      0.26; P=0.02). Log FGF23 predicted CKD progression in crude models and after
      adjustment for mineral metabolites (endpoints 2A and 2B). It remained significant
      after adjustments for age, sex, serum albumin, calcium, phosphate, parathyroid
      hormone, 25-hydroxyvitamin D, baseline albuminuria, baseline estimated GFR, mean
      arterial BP, body mass index, and angiotensin-converting enzyme
      inhibitors/angiotensin-receptor blocker use in endpoint 2B (hazard ratio, 2.53;
      P=0.02) but not endpoint 2A (hazard ratio, 2.01; P=0.43). Log FGF23 predicted
      annual loss of estimated GFR in the same model (change in ml/min per 1.73 m(2)
      per increase in log FGF23, 1.50; P=0.008). CONCLUSIONS: In patients with CKD and
      IgAN, FGF23 was associated with albuminuria and CKD progression, a finding that
      suggests its role as a potential biomarker in IgAN.

PMID- 22383748
TI  - Racial differences in markers of mineral metabolism in advanced chronic kidney
      disease.
AB  - BACKGROUND AND OBJECTIVES: This study examined differences in the concentration
      of markers of mineral metabolism across race in patients with advanced CKD not
      requiring dialysis and ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Concentrations of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D
      (1,25(OH)(2)D), intact parathyroid hormone (iPTH), and fibroblast growth factor
      23 (FGF-23) were measured in stored plasma samples of 1497 patients with advanced
      CKD not yet on dialysis and ESRD who participated in the Homocysteine in Kidney
      and End Stage Renal Disease study. Linear regression models were used to examine
      the relationship between race and 25(OH)D, 1,25(OH)(2)D, iPTH, and FGF-23
      concentrations. RESULTS: Non-Hispanic white patients comprised 58% of the cohort,
      whereas non-Hispanic blacks comprised 42%. Median (interquartile range) FGF-23
      concentrations were lower in blacks compared with whites with CKD (323 [181-655]
      versus 431 [232-1026] RU/ml; P<0.001) but not in ESRD. In adjusted linear
      regression models, blacks with CKD not requiring dialysis had significantly lower
      plasma FGF-23 concentrations (difference, -159; 95% confidence interval, -205 to 
      106; P<0.001) compared with whites, independent of plasma 25(OH)D, 1,25(OH)(2)D,
      and iPTH concentrations. This difference was not observed in the ESRD group. The
      magnitude of correlation for the relationships between 1,25(OH)(2)D with iPTH,
      FGF-23 with 1,25(OH)(2)D, and FGF-23 with iPTH were stronger among blacks than
      whites with CKD not requiring dialysis. CONCLUSIONS: In advanced CKD not
      requiring dialysis, blacks have lower FGF-23 concentrations than whites. Blacks
      with CKD and ESRD have lower 25(OH)D and higher iPTH compared with whites,
      independent of FGF-23 concentrations.

PMID- 22383749
TI  - Chronic kidney disease, insulin resistance, and incident diabetes in older
      adults.
AB  - BACKGROUND AND OBJECTIVES: Insulin resistance is a complication of advanced CKD.
      Insulin resistance is less well characterized in earlier stages of CKD. The
      response of the pancreatic beta cell, effects on glucose tolerance, and risk of
      diabetes are not clear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The
      Cardiovascular Health Study included 4680 adults without baseline diabetes. The
      Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to
      obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting
      insulin concentration. The insulin sensitivity index, beta cell function, and
      glucose tolerance were assessed by oral glucose tolerance testing. Incident
      diabetes was defined as fasting glucose >=126 mg/dl, nonfasting glucose >=200
      mg/dl, or use of glucose-lowering medications. RESULTS: Mean age was 72.5 years
      (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After
      adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2%
      higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%;
      P<0.001) and a 1.1% lower insulin sensitivity index (95% CI, 0.03%, 2.2%;
      P=0.04). Surprisingly, eGFR was associated with an augmented beta cell function
      index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk
      of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437
      participants (9.3%) developed diabetes. eGFR was not associated with the risk of
      incident diabetes. CONCLUSIONS: Among older adults, lower eGFR was associated
      with insulin resistance. However, with lower eGFR, beta cell function was
      appropriately augmented and risks of impaired glucose tolerance and incident
      diabetes were not increased.

PMID- 22383750
TI  - Influence of urine creatinine on the relationship between the albumin-to
      creatinine ratio and cardiovascular events.
AB  - BACKGROUND AND OBJECTIVES: In the albumin-to-creatinine ratio (spot-ACR), urine
      creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass
      is associated with cardiovascular disease (CVD). We hypothesized that the spot
      ACR would be higher in women, lower-weight persons, and older individuals,
      independent of timed urine albumin excretion (24hr-UAE), and accordingly, that
      spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these
      subgroups. DESIGN, SETTING, PARTICIPANTS, & METHODS: 2627 PREVEND (Prevention of
      Renal and Vascular End-stage Disease) participants with 24hr-UAE <30 mg/d were
      followed for CVD events for 11 years. Cox regression evaluated associations of
      spot-ACR and 24hr-UAE with CVD events by sex, weight, and age. RESULTS: Female
      sex (26%), lower weight (2% per 5 kg), and older age (4% per 5 years) were
      associated with higher spot-ACR independent of 24hr-UAE (P<0.001). Spot urine
      albumin concentration (hazard ratio [HR], 1.26 per ln-SD higher) and 1/spot urine
      creatinine concentration (HR, 1.16 per ln-SD higher) were associated with CVD
      events. Spot-ACR was more strongly associated with CVD events than either
      component of the ratio (HR, 1.41 per ln-SD higher). Associations of spot-ACR >=10
      mg/g versus less (HR, 2.33) and 24hr-UAE >=10 mg/d versus less (HR, 2.09) with
      CVD events were similar, and there were no significant differences across
      subgroups (P for interactions >0.06). CONCLUSIONS: In community-living
      individuals with 24hr-UAE <30 mg/d, spot-ACR is higher in women, older persons,
      and lower-weight persons, independent of 24hr-UAE. Low spot urine creatinine is
      associated with CVD risk, but high urine albumin is a stronger determinant of the
      association of spot-ACR with CVD than is low urine creatinine.

PMID- 22383751
TI  - The accuracy of point-of-care glucose measurement.

PMID- 22383753
TI  - Natural killer cell tolerance: control by self or self-control?
AB  - A major challenge for the immune system is to control pathogens and stressed
      cells, such as infected or tumors cells, while sparing healthy self-cells. To
      achieve this tolerance to self, immune cells must recognize and differentiate
      "self" versus "nonself" and "self" versus "altered self." In the absence of self
      tolerance, cells of the adaptive immune system attack healthy cells and cause
      autoimmune diseases such as lupus, psoriasis, and type I diabetes. Mechanisms at
      work to ensure tolerance in the innate immune system are still poorly understood.
      Natural killer cells are innate immune lymphocytes, which have the capacity to
      kill cellular targets and produce cytokines without prior specific sensitization.
      Because of these intrinsic effector capacities, tolerance mechanisms must exist
      to prevent autoreactivity. Herein, we will review the present knowledge on NK
      cell tolerance.

PMID- 22383755
TI  - The Jak/STAT pathway.

PMID- 22383756
TI  - On in vivo imaging in cancer.

PMID- 22383754
TI  - The immunogenetic architecture of autoimmune disease.
AB  - The development of most autoimmune diseases includes a strong heritable
      component. This genetic contribution to disease ranges from simple Mendelian
      inheritance of causative alleles to the complex interactions of multiple weak
      loci influencing risk. The genetic variants responsible for disease are being
      discovered through a range of strategies from linkage studies to genome-wide
      association studies. Despite the rapid advances in genetic analysis, substantial
      components of the heritable risk remain unexplained, either owing to the
      contribution of an as-yet unidentified, "hidden," component of risk, or through
      the underappreciated effects of known risk loci. Surprisingly, despite the
      variation in genetic control, a great deal of conservation appears in the
      biological processes influenced by risk alleles, with several key immunological
      pathways being modified in autoimmune diseases covering a broad spectrum of
      clinical manifestations. The primary translational potential of this knowledge is
      in the rational design of new therapeutics to exploit the role of these key
      pathways in influencing disease. With significant further advances in
      understanding the genetic risk factors and their biological mechanisms, the
      possibility of genetically tailored (or "personalized") therapy may be realized.

PMID- 22383757
TI  - On chromatin remodeling in mammary gland differentiation and breast
      tumorigenesis.

PMID- 22383759
TI  - Cross talk between estradiol and mTOR kinase in the regulation of ovarian
      granulosa proliferation.
AB  - Treatment of ovarian granulosa cells and follicles with the mammalian target of
      rapamycin (mTOR) kinase inhibitor results in biphasic effects where nanomolar
      rapamycin (RAP) results in reduced proliferation, mitotic anomalies, and
      attenuated follicle growth, while the picomolar RAP results in accelerated
      follicle growth. Here, we tested whether such effects are specific to RAP or
      could be mimicked by 2 alternative mTOR inhibitors, everolimus (EV) and
      temsirolimus (TEM), and whether these effects were dependent on the presence of
      estradiol (E2). Spontaneously immortalized rat granulosa cells (SIGCs) were
      cultured in dose curves of RAP, EV, TEM, or vehicle with or without E2.
      Proliferation and phosphorylation of mTOR targets p70S6 kinase and 4E-binding
      protein (BP) were determined. Cell cycle gene array analysis and confirmatory
      quantitative reverse transcriptase polymerase chain reaction were performed upon
      cells treated with picomolar RAP versus controls. Nanomolar RAP, EV, and TEM
      reduced SIGC proliferation and decreased phospho-p70 and 4E-BP. Picomolar
      concentrations accelerated proliferation without affecting mTOR substrate
      phosphorylation. Acceleration of growth by picomolar inhibitor required E2.
      Picomolar drug treatment altered the transcription of cell cycle regulators,
      increasing Integrin beta 1 and calcineurin expression, and decreasing inhibin
      alpha, Chek1, p16ARF, p27/Kip1, and Sestrin2 expression. At nanomolar
      concentrations, mTOR inhibitors attenuated granulosa proliferation. Accelerated
      growth and alterations in cell cycle gene transcription found with picomolar
      concentrations required E2 within the intrafollicular concentration range. The
      low concentrations of inhibitors required to increase granulosa proliferation
      suggest a novel use to support the growth of ovarian follicles.

PMID- 22383761
TI  - Psychopathy in childhood: is it a meaningful diagnosis?
AB  - Psychopathy is not included in either of the main classification systems (ICD-10
      or DSM-IV). Research has now extended the concept of psychopathy to childhood and
      has produced evidence that it is meaningfully distinct from antisocial behaviour.
      It is proposed that psychopathy should be accepted as a meaningful diagnosis in
      childhood.

PMID- 22383760
TI  - Premenopausal women exhibit an inherent protection of endothelial function
      following a high-fat meal.
AB  - Endogenous estrogens likely increase blood flow and subsequently shear stress but
      have also been associated with improved endothelial function and cardiovascular
      protection. In contrast, a high-fat meal is thought to reduce endothelial
      function and increase cardiovascular risk. Therefore, we tested the hypotheses
      that fluctuating hormones across the menstrual cycle (1) facilitate an increase
      in shear rate and explain phase-specific differences in flow-mediated dilation
      (FMD) and (2) provide vascular protection against the insult of a high-fat meal.
      Flow-mediated dilation was determined at baseline and 4 hours following a high
      fat meal in young women during the menses (M), follicular (F), and luteal (L)
      phases of the menstrual cycle. Male control participants were studied once.
      17beta-Estradiol was elevated (P < .05) during the F (5.3 +/- 0.7 pg/mL) and L
      (5.2 +/- 0.6 pg/mL) phases when compared to the M (3.9 +/- 0.5 pg/mL) phase, and
      this was accompanied by an elevated FMD in the F and L phases (12.4 +/- 1.4% and
      11.2 +/- 0.9%, respectively) compared to M (8.0 +/- 0.9) with no change in shear
      rate. Female postprandial FMD was similar throughout the menstrual cycle, while
      men exhibited a 50% reduction (6.4 +/- 1 to 3.3 +/- 1%; P < .05). Interestingly,
      the postprandial FMD response was not associated with concentrations of either
      17beta-estradiol or progesterone. Despite acutely changing ovarian hormones
      across the menstrual cycle, shear stress is invariant and therefore does not
      account for the changes in FMD. Additionally, young women appear to have an
      inherent vascular protection from the insult of a high-fat meal, perhaps helping
      to explain sex-specific differences in cardiovascular risk.

PMID- 22383762
TI  - Why should we care about measuring callous-unemotional traits in children?
AB  - Callous-unemotional traits consist of lack of empathy, guilt and shallow affect.
      A growing body of research suggests that the presence of these traits are of
      clinical significance, even if they occur in the absence of concurrent antisocial
      behaviour.

PMID- 22383763
TI  - Comorbid anxiety and depression: bete noire or quick fix?
AB  - The common territory shared by anxiety and depression has always been a
      contentious subject. Research in favour of anxious depression as a potentially
      treatment-relevant subtype has been limited by diagnostic dilemmas and crude
      measurement. The most recent evidence from genetics, neuropeptide systems and
      functional neuroimaging suggests a valid diagnostic construct.

PMID- 22383764
TI  - The Equality Act 2010 and mental health.
AB  - One aim of the Equality Act 2010 is to protect people with disabilities and
      prevent disability discrimination. We review the key provisions of the Act
      relevant to disability discrimination with respect to mental illness.

PMID- 22383765
TI  - Group psychological therapies for depression in the community: systematic review
      and meta-analysis.
AB  - BACKGROUND: Psychological therapies have been shown to be effective in the
      treatment of depression. However, evidence is focused on individually delivered
      therapies, with less evidence for group-based therapies. AIMS: To conduct a
      systematic review and meta-analysis of the efficacy of group-based psychological
      therapies for depression in primary care and the community. METHOD: We searched
      MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials and
      the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group database
      from inception to July 2010. The Cochrane risk of bias methodology was applied.
      RESULTS: Twenty-three studies were included. The majority showed considerable
      risk of bias. Analysis of group cognitive-behavioural therapy (CBT) v. usual care
      alone (14 studies) showed a significant effect in favour of group CBT immediately
      post-treatment (standardised mean difference (SMD) -0.55 (95% CI -0.78 to 
      0.32)). There was some evidence of benefit being maintained at short-term (SMD = 
      0.47 (95% CI -1.06 to 0.12)) and medium- to long-term follow-up (SMD = -0.47 (95%
      CI - 0.87 to -0.08)). Studies of group CBT v. individually delivered CBT therapy
      (7 studies) showed a moderate treatment effect in favour of individually
      delivered CBT immediately post-treatment (SMD = 0.38 (95% CI 0.09-0.66)) but no
      evidence of difference at short- or medium- to long-term follow-up. Four studies
      described comparisons for three other types of group psychological therapies.
      CONCLUSIONS: Group CBT confers benefit for individuals who are clinically
      depressed over that of usual care alone. Individually delivered CBT is more
      effective than group CBT immediately following treatment but after 3 months there
      is no evidence of difference. The quality of evidence is poor. Evidence about
      group psychological therapies not based on CBT is particularly limited.

PMID- 22383766
TI  - Patients' experience of dangerous and severe personality disorder services:
      qualitative interview study.
AB  - As part of an evaluation of the Dangerous and Severe Personality Disorder (DSPD)
      Programme, we conducted in-depth interviews with 60 participants purposely
      sampled across four pilot DSPD units. This report is limited to the finding with
      potential 'conceptual generalisability': namely the unanticipated finding of
      negative and hostile attitudes of participants being managed in hospital units
      compared with the prison system. The recent UK government policy decision to
      concentrate this programme in prisons may, in part, reflect the significance of
      these findings.

PMID- 22383767
TI  - Predicting the development of schizophrenia.

PMID- 22383768
TI  - Predicting the development of schizophrenia.

PMID- 22383770
TI  - Abortion, mental health and charges of guilt by association.

PMID- 22383771
TI  - The fall of the atypicals?

PMID- 22383775
TI  - Importance of vaginal microbes in reproductive health.
AB  - Over 250 species of bacteria have been detected in the vagina using genomic
      sequencing. Lactobacillus iners and L crispatus dominate in most women who have a
      clinically healthy status. Unfortunately, the abundance profiles can change
      dramatically with significant increases in pathogens associated with bacterial
      vaginosis (BV) and aerobic vaginitis (AV). The BV microbiota have at least 4
      different abundance profiles, indicating this is a complex condition, yet one
      that is treated with essentially 2 antimicrobial agents which were never designed
      for eradicting these organisms in dense biofilms. Future studies will uncover
      which abundance profiles are particularly associated with a risk of preterm
      labor, and hopefully identify the mechanisms involved in the switch from healthy
      to a BV or AV state. The use of probiotic lactobacilli vaginally and orally has
      shown great promise in helping to restore and maintain a healthy vagina, and
      studies have shown that certain strains have the capacity to interfere with the
      inflammatory pathway leading to preterm delivery. There is enormous need for new
      diagnostic and therapeutic modalities, especially to save the lives of millions
      of babies in resource-disadvantaged countries.

PMID- 22383776
TI  - In vitro culture of mouse embryos reduces differential gene expression between
      inner cell mass and trophectoderm.
AB  - Differences in gene expression and imprinting have been reported, comparing in
      vivo versus in vitro generated preimplantation embryos. Furthermore, mouse
      studies have shown that placenta development is altered following in vitro
      culture. However, the molecular mechanisms underlying these findings are unknown.
      We therefore isolated trophectoderm (TE) and inner cell mass (ICM) cells from in
      vivo and in vitro fertilization (IVF) embryos and evaluated their transcriptome
      using microarrays. We found that the transcriptomes of in vitro produced ICM and
      TE cells showed remarkably few differences compared to ICM and TE cells of in
      vivo generated embryos. In vitro fertilization embryos showed a reduced number of
      TE cells compared to in vivo embryos. In addition, TE of IVF embryos showed
      significant downregulation of solute transporter genes and of genes involved in
      placenta formation (Eomesodermin, Socs3) or implantation (Hbegf). In summary, IVF
      and embryo culture significantly affects the transcriptome of ICM and TE cells.

PMID- 22383777
TI  - Histopathological and immunohistochemical changes in the testes of rabbits after
      injection with the growth promoter boldenone.
AB  - Recently, boldenone (androgenic steroid) is used in improvement of the growth and
      food conversion in food-producing animals. In addition, it is used by
      bodybuilders during both off-season and precontest, where it is well known for
      increasing vascularity while preparing for a bodybuilding contest. The present
      study was designed to investigate the possible effect of growth promoter
      boldenone undecylenate on the structure and functions of rabbit testes. A total
      of 32 adult New Zealand rabbits were divided into 4 groups. The first group in
      the control group includes animals that were intramuscularly injected with olive
      oil and dissected after 3 weeks. Three experimental groups include animals that
      receive 1, 2, and 3 intramuscular injections of 5 mg/kg body weight boldenone,
      and dissected after 3, 6, and 9 weeks, respectively. Treating rabbits with
      boldenone increased the testosterone levels compared to the control group.
      Seminiferous tubules of the rabbit testis treated with boldenone showed reduced
      development and degeneration of the germinal epithelium, leading to debris and
      syncytial cell formation in the lumina of seminiferous tubules. Our
      immunohistochemical results indicated severe reduction in proliferating cell
      nuclear antigen-positive spermatogonia in boldenone-treated animals as compared
      to the control group. These findings explain the common phenomena among athletics
      and bodybuilders who suffer from infertility as they were injected with some
      drugs such as steroids (boldenone) to build muscles.

PMID- 22383778
TI  - Differential effect of intrauterine hypoxia on caspase 3 and DNA fragmentation in
      fetal guinea pig hearts and brains.
AB  - The aim of this study is to quantify the effect of intrauterine hypoxia (HPX) and
      the role of nitric oxide (NO) on the apoptotic enzyme, caspase 3, and DNA
      fragmentation in fetal heart and brain. Hypoxia and NO are important regulators
      of apoptosis, although this has been little studied in the fetal organs. We
      investigated the effect of intrauterine HPX on apoptosis and the role of NO in
      both fetal hearts and brains. Pregnant guinea pigs were exposed to room
      temperature (N = 14) or 10.5% O2 (N = 12) for 14 days prior to term (term = 65
      days) and administered water or L-N6-(1-iminoethyl)-lysine (LNIL), an inducible
      nitric oxide synthase (iNOS) inhibitor, for 10 days. Fetal hearts and brains were
      excised from anesthetized near-term fetuses for study. Chronic HPX decreased pro-
      and active caspase 3, caspase 3 activity, and DNA fragmentation levels in fetal
      hearts compared with normoxic controls. L-N6-(1-iminoethyl)-lysine prevented the
      HPX-induced decrease in caspase 3 activity but did not alter DNA fragmentation
      levels. In contrast, chronic HPX increased both apoptotic indices in fetal
      brains, which were inhibited by LNIL. Thus, the effect of HPX on apoptosis
      differs between fetal organs, and NO may play an important role in modulating
      these effects.

PMID- 22383779
TI  - Computer-assisted oocyte morphometry before ICSI: correlation of oocyte
      measurements with fertilization and embryo development.
AB  - The present study aimed to correlate morphometric parameters of the oocytes with
      the occurrence of fertilization following intracytoplasmic sperm injection
      (ICSI). In a prospective, controlled cohort design, women (n = 32) who were
      candidates for ICSI had oocytes (n = 258) collected and submitted to morphometric
      evaluation using the Cronus3 software program. The morphometric parameters
      obtained were oocyte diameter, perivitelline space width, zona pellucida
      thickness, and first polar body diameter. The median oocyte diameter was similar
      in cases in which fertilization occurred compared with those in which
      fertilization failed (75.2 and 75.9 MUm, respectively; P = .218). The 2 groups
      also had similar measurements of perivitelline space, zona pellucida, and first
      polar body. However, the best quality zygotes identified by a morphological score
      resulted from oocytes with larger diameter (75.6 vs 74.0 MUm; P < .01) and narrow
      perivitelline space (5.3 vs 7.1 MUm; P < .01). Embryo development, as assessed by
      cleavage at second day of culture, was not significantly associated with oocyte
      morphometric parameters. These findings suggest that morphometric parameters of
      the oocytes do not correlate with the occurrence of fertilization following ICSI
      but may assist in selecting oocytes more likely to originate high-quality
      zygotes.

PMID- 22383780
TI  - Combined effect of GSTT1 and GSTM1 polymorphisms on human male infertility in
      north Indian population.
AB  - Genes of different pathways regulate spermatogenesis, and complexity of
      spermatogenic process indicates that polymorphisms or mutations in these genes
      could cause male infertility. Detoxification pathway is involved in the
      regulation of spermatogenesis by reducing oxidative stress and contributes to the
      maintenance of global methylation in concert with other pathways. Glutathione S
      transferases (GSTs) belong to the family of phase II antioxidant enzymes involved
      in the cellular detoxification of various physiological substances. Glutathione S
      transferases act as an antioxidant and protect spermatozoa from oxidative stress.
      Increase in the levels of reactive oxygen species (ROS) along with reduced
      activity of GSTs may result in sperm membrane damage and DNA fragmentation. A
      case-control study was done to elucidate the role of deletion polymorphism of
      GSTT1 and GSTM1 genes from GSTs family on idiopathic human male infertility. The
      study comprises 2 groups: 113 nonobstructive azoospermia patients and 91 healthy
      fertile controls. Genomic DNA was analyzed by polymerase chain reaction for GSTT1
      and GSTM1 genes. The study showed statistically significant protective
      association of GSTT1 null genotype with human male infertility (odds ratio [OR]:
      0.3, 95% confidence interval [CI] 0.143-0.9966, P = .048) but not with GSTM1 null
      genotype (OR: 0.66, 95% CI 0.3653-1.2234, P = .19). Also, combination of null
      genotypes of GSTM1 and GSTT1 confers protective effect (OR: 0.28, CI 0.0801
      0.948; P = .04). Probably, individuals bearing GSTM1 and GSTT1 (-/-) genotypes
      may have protective effect by gene-gene interaction mechanism. In summary, our
      study underscores the significance of combined effect of GSTT1 and GSTM1 null
      genotypes in modulating the risk of male infertility.

PMID- 22383781
TI  - Factor seven activating protease activity levels in women with recurrent
      pregnancy loss.
AB  - This study was designed to analyze the changes in circulating factor seven
      activating protease (FSAP) levels in association with the thrombophilic state of
      40 women with recurrent pregnancy loss (RPL). All women were trying to conceive
      and were prospectively followed up until the achievement of spontaneous
      pregnancy. The results obtained showed that plasma FSAP activity levels were
      higher in RPL than in fertile women (P < .001) and represented an adverse
      predictor of pregnancy at multivariate analysis (P = .002). In 7 consenting RPL
      women, FSAP activity levels increased continuously during pregnancy until the
      third trimester, remained elevated immediately after delivery, and declined 6
      week postpartum, although at levels that were still above the range of control
      women. These results suggest that FSAP activity levels might provide useful
      information during pregnancy progression in at-risk women, possibly acting as a
      predictive factor for adverse pregnancy outcome in RPL even in the absence of
      other well recognized thrombophilic conditions.

PMID- 22383782
TI  - Impact of experimental diabetes on the maternal uterine vascular remodeling
      during rat pregnancy.
AB  - Normal pregnancy is associated with an increase in uteroplacental blood flow in
      part due to growth and remodeling of the maternal uterine vasculature. In this
      study, we characterized the effect of diabetic pregnancy on vascular growth of
      the maternal uterine vasculature and on the passive mechanical properties of the
      uterine resistance arteries. Diabetes was induced in pregnant rats by injection
      of streptozotocin and confirmed by development of hyperglycemia. Fetuses of
      diabetic rats were significantly smaller and placentas larger compared to
      controls. Pregnancy-induced axial elongation of the mesometrial uterine
      vasculature was not altered by diabetes. Vascular wall thickness was unchanged
      between groups. Wall distensibility was increased and the rate constant of an
      exponential function fitted to stress-strain curve was significantly reduced
      demonstrating decreased wall stiffness in diabetic uterine radial arteries
      compared to controls. We conclude that experimental diabetes in rat pregnancy
      does not compromise the growth of maternal uterine vasculature but alters passive
      mechanical properties of the uterine radial arteries.

PMID- 22383784
TI  - Analysis of pneumatization and neurovascular structures of the sphenoid sinus
      using cone-beam tomography (CBT).
AB  - BACKGROUND: The sphenoid sinus is a frequent target of paranasal sinus surgery.
      Because of the high risk of injuring the surrounding structures (e.g. internal
      carotid artery, optical nerve) a preoperative imaging is absolutely necessary.
      PURPOSE: To analyze the possibilities of cone-beam computed tomography (CBCT),
      which is especially quite a new technique in ENT, in the evaluation of the
      sphenoid sinus, its surrounding structures, and the corresponding anatomical
      variations. MATERIAL AND METHODS: This was a retrospective, single-centre study
      of 580 patients (1160 sides = cases). The Accu-I-Tomo-F17 was used.
      Pneumatization of sphenoid sinus, course of internal artery, course of optical
      nerve, and dehiscence of the bony canals were evaluated. RESULTS: In the case of
      pneumatization a type I (completely missing or minimal sphenoid sinus) was found
      in two patients (0.3%), type II (posterior wall of sphenoid sinus is in front of
      the anterior wall of the sella) in 38 patients (6.6%), type III (posterior wall
      is between anterior and posterior wall of sella) in 332 patients (57,2%), type
      IVa (posterior wall is behind the posterior wall of sella without air dorsal the
      sella) in 104 patients (17.9%), and type IVb (similar to type IVa but with air
      dorsal the sella) in 104 patients (17.9%). In 1025 cases (89.5%) a smooth course
      of the internal carotid artery was found whereas a free course could be detected
      in 120 cases (10.5%). Defects of the bony canal of the optical nerve were found
      in 16.7% and of the internal carotid artery in 2.7% of the cases. The optical
      nerve showed a free course through the sphenoid in 151 cases (13.7%) and a smooth
      course in 1007 cases (87.0%). CONCLUSION: CBCT could evaluate all relevant
      anatomic structures and answer the questions of different anatomical variants. A
      modified classification of the pneumatization of the sphenoid sinus could be
      described. Frequencies of anatomical variations are in accordance with the
      current literature of CT research.

PMID- 22383787
TI  - Taking it up a notch in MCL.
AB  - In this issue of Blood, Kridel et al describe recurrent NOTCH1 mutations in
      mantle cell lymphoma (MCL) by next-generation sequencing of patient samples and
      cell lines. They further demonstrate a negative prognostic impact of NOTCH1
      mutation in their cohort of patients and sensitivity of MCL cells to NOTCH1
      inhibition in vitro, suggesting a novel role for NOTCH1 in this disease.

PMID- 22383788
TI  - Unveiling the complexity of CK+ AML.
AB  - In acute myeloid leukemia (AML), cytogenetic abnormalities are present in more
      than half of patients and these chromosomal alterations are critical factors that
      determine response to chemotherapy and survival.

PMID- 22383789
TI  - VWF sequence variants: innocent until proven guilty.
AB  - William James, the 19th century American philosopher, famously asserted, "To
      study the abnormal is the best way of understanding the normal." In this issue of
      Blood, using a distinctly non-Jamesian approach, Bellissimo and colleagues shed
      new light on our understanding of normal genetic variation in von Willebrand
      factor (VWF) through the study of ethnically diverse healthy controls and, in
      doing so, exonerate a number of benign sequence variants previously regarded as
      pathogenic mutations.

PMID- 22383790
TI  - Experience with obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family
      antagonist in patients with relapsed or refractory classical Hodgkin lymphoma.

PMID- 22383791
TI  - Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran
      associated postcardiac surgery bleeding.

PMID- 22383792
TI  - Circulating immune complexes do not affect microparticle flow cytometry analysis
      in acute coronary syndrome.

PMID- 22383793
TI  - Fingolimod blocks immunosurveillance of myeloma and B-cell lymphoma resulting in
      cancer development in mice.

PMID- 22383794
TI  - CEBPE activation in PML-RARA cells by arsenic.

PMID- 22383795
TI  - Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with
      mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new
      treatment strategies. The associated t(11:14) translocation results in enhanced
      cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell
      cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor
      PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2
      [(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron
      emission tomography (PET) to study tumor metabolism and proliferation,
      respectively, in concert with pre- and on-treatment lymph node biopsies to assess
      retinoblastoma protein (Rb) phosphorylation and markers of proliferation and
      apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake
      value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred
      after 3 weeks in most patients, with significant correlations among these end
      points. Five patients achieved progression-free survival time of > 1 year (range,
      14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective
      response rate; 90% confidence interval, 5%-40%). These patients demonstrated >
      70%, > 90%, and >= 87.5% reductions in summed FLT SUV(max) and expression of
      phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for
      long-term disease control. The results of the present study confirm CDK4/6
      inhibition by PD0332991 at a well-tolerated dose and schedule and suggest
      clinical benefit in a subset of MCL patients. This study is registered at
      www.clinicaltrials.gov under identifier NCT00420056.

PMID- 22383796
TI  - Acute myeloid leukemia in the real world: why population-based registries are
      needed.
AB  - Population-based registries may provide data complementary to that from basic
      science and clinical intervention studies, all of which are essential for
      establishing recommendations for the management of patients in the real world.
      The same quality criteria apply for the evidence-based label, and both high
      representation and good data quality are crucial in registry studies. Registries
      with high coverage of the target population reduce the impact of selection on
      outcome and the subsequent problem with extrapolating data to nonstudied
      populations. Thus, data useful for clinical decision in situations not well
      covered by clinical studies can be provided. The potential clinical impact of
      data from population-based studies is exemplified with analyses from the Swedish
      Acute Leukemia Registry containing more than 3300 acute myeloid leukemia (AML)
      patients diagnosed between 1997 and 2006 with a median follow-up of 6.2 years on
      (1) the role of intensive combination chemotherapy for older patients with AML,
      (2) the impact of allogeneic stem cell transplantation on survival of younger
      patients with AML, and (3) the continuing problem with early deaths in acute
      promyelocytic leukemia. We also present the first Web-based dynamic graph showing
      the complex interaction between age, performance status, the proportion of
      patients given intensive treatment, early death rate, complete remission rate,
      use of allogeneic transplants, and overall survival in AML (non-AML).

PMID- 22383797
TI  - Btk levels set the threshold for B-cell activation and negative selection of
      autoreactive B cells in mice.
AB  - On antigen binding by the B-cell receptor (BCR), B cells up-regulate protein
      expression of the key downstream signaling molecule Bruton tyrosine kinase (Btk),
      but the effects of Btk up-regulation on B-cell function are unknown. Here, we
      show that transgenic mice overexpressing Btk specifically in B cells
      spontaneously formed germinal centers and manifested increased plasma cell
      numbers, leading to antinuclear autoantibody production and systemic lupus
      erythematosus (SLE)-like autoimmune pathology affecting kidneys, lungs, and
      salivary glands. Autoimmunity was fully dependent on Btk kinase activity, because
      Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and
      differentiation, and because autoantibodies were absent in Btk transgenic mice
      overexpressing a kinase inactive Btk mutant. B cells overexpressing wild-type Btk
      were selectively hyperresponsive to BCR stimulation and showed enhanced Ca(2+)
      influx, nuclear factor (NF)-kappaB activation, resistance to Fas-mediated
      apoptosis, and defective elimination of selfreactive B cells in vivo. These
      findings unravel a crucial role for Btk in setting the threshold for B-cell
      activation and counterselection of autoreactive B cells, making Btk an attractive
      therapeutic target in systemic autoimmune disease such as SLE. The finding of in
      vivo pathology associated with Btk overexpression may have important implications
      for the development of gene therapy strategies for X-linked agammaglobulinemia,
      the immunodeficiency associated with mutations in BTK.

PMID- 22383798
TI  - Galectin-1 inhibits the viability, proliferation, and Th1 cytokine production of
      nonmalignant T cells in patients with leukemic cutaneous T-cell lymphoma.
AB  - Tumor-derived galectin-1 (Gal-1), a beta-galactoside-binding S-type lectin, has
      been shown to encourage T-cell death and promote T cell-mediated tumor immune
      escape. In this report, we show that patients with leukemic cutaneous T-cell
      lymphomas, known to have limited complexity of their T-cell repertoires, have a
      predominant T helper type-2 (Th2) cytokine profile and significantly elevated
      plasma levels of Gal-1 compared with healthy controls. Circulating clonal
      malignant T cells were a major source of Gal-1. The conditioned supernatant of
      cultured malignant T cells induced a beta-galactoside-dependent inhibition of
      normal T-cell proliferation and a Th2 skewing of cytokine production. These data
      implicate Gal-1 in development of the Th2 phenotype in patients with advanced
      stage cutaneous T-cell lymphoma and highlight the Gal-1-Gal-1 ligand axis as a
      potential therapeutic target for enhancing antitumor immune responses.

PMID- 22383799
TI  - Chromatin occupancy analysis reveals genome-wide GATA factor switching during
      hematopoiesis.
AB  - There are many examples of transcription factor families whose members control
      gene expression profiles of diverse cell types. However, the mechanism by which
      closely related factors occupy distinct regulatory elements and impart lineage
      specificity is largely undefined. Here we demonstrate on a genome wide scale that
      the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes,
      often at distinct sites, as a means to differentially regulate target gene
      expression and to regulate the balance between proliferation and differentiation.
      We also reveal that the GATA switch, which entails a chromatin occupancy exchange
      between GATA2 and GATA1 in the course of differentiation, operates on more than
      one-third of GATA1 bound genes. The switch is equally likely to lead to
      transcriptional activation or repression; and in general, GATA1 and GATA2 act
      oppositely on switch target genes. In addition, we show that genomic regions co
      occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions
      marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy
      in erythroid cells and megakaryocytes, we find that the presence of ETS factor
      motifs is a major discriminator of megakaryocyte versus red cell specification.

PMID- 22383800
TI  - Acute graft-versus-host disease biomarkers measured during therapy can predict
      treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study.
AB  - Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic
      hematopoietic cell transplantation, and once it develops, there are no reliable
      diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously
      validated diagnostic biomarkers of GVHD (IL-2 receptor-alpha; tumor necrosis
      factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific
      marker; and regenerating islet-derived 3-alpha, a gastrointestinal tract-specific
      marker) could discriminate between therapy responsive and nonresponsive patients
      and predict survival in patients receiving GVHD therapy. We measured GVHD
      biomarker concentrations from samples prospectively obtained at the initiation of
      treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2
      clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time
      points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6
      protein biomarker panel predicted for the important clinical outcomes of day 28
      posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker
      panels can be used for early identification of patients at high or low risk for
      treatment nonresponsiveness or death, and they may provide opportunities for
      early intervention and improved survival after hematopoietic cell
      transplantation. The study was registered in clinicaltrials.gov as NCT00224874.

PMID- 22383802
TI  - A pilot test of a tailored mobile and web-based diabetes messaging system for
      adolescents.
AB  - We conducted a pilot trial of a new mobile and web-based intervention to improve
      diabetes adherence. The text messaging system was designed to motivate and remind
      adolescents about diabetes self-care tasks. Text messages were tailored according
      to individually-reported barriers to diabetes self-care. A total of 23
      adolescents with type 1 diabetes used the system for a period of three months. On
      average, they received 10 text messages per week (range 8-12). A matched
      historical control group from the same clinic was used for comparison. After
      three months, system users rated the content, usability and experiences with the
      system, which were very favourable. Comparison of the intervention and control
      groups indicated a significant interaction between group and time. Both groups
      had similar HbA(1c) levels at baseline. After three months, the mean HbA(1c)
      level in the intervention group was unchanged (8.8%), but the mean level in the
      control group was significantly higher (9.9%), P = 0.006. The results demonstrate
      the feasibility of the messaging system, user acceptance and a promising effect
      on glycaemic control. Integrating this type of messaging system with online
      educational programming could prove to be beneficial.

PMID- 22383801
TI  - Tim-3 marks human natural killer cell maturation and suppresses cell-mediated
      cytotoxicity.
AB  - Natural killer (NK) cells are innate lymphocytes that play an important role
      against viral infections and cancer. This effect is achieved through a complex
      mosaic of inhibitory and activating receptors expressed by NK cells that
      ultimately determine the magnitude of the NK-cell response. The T-cell
      immunoglobulin- and mucin domain-containing (Tim)-3 receptor was initially
      identified as a T-helper 1-specific type I membrane protein involved in
      regulating T-cell responses. Human NK cells transcribe the highest amounts of Tim
      3 among lymphocytes. Tim-3 protein is expressed on essentially all mature
      CD56(dim)CD16(+) NK cells and is expressed heterogeneously in the immature
      CD56(bright)CD16(-) NK-cell subset in blood from healthy adults and in cord
      blood. Tim-3 expression was induced on CD56(bright)CD16(-) NK cells after
      stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a
      maturation marker on NK cells. Whereas Tim-3 has been used to identify
      dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully
      responsive with respect to cytokine production and cytotoxicity. However, when
      Tim-3 was cross-linked with antibodies it suppressed NK cell-mediated
      cytotoxicity. These findings suggest that NK-cell responses may be negatively
      regulated when NK cells encounter target cells expressing cognate ligands of Tim
      3.

PMID- 22383803
TI  - Own-gender imitation activates the brain's reward circuitry.
AB  - Imitation is an important component of human social learning throughout life.
      Theoretical models and empirical data from anthropology and psychology suggest
      that people tend to imitate self-similar individuals, and that such imitation
      biases increase the adaptive value (e.g., self-relevance) of learned information.
      It is unclear, however, what neural mechanisms underlie people's tendency to
      imitate those similar to themselves. We focused on the own-gender imitation bias,
      a pervasive bias thought to be important for gender identity development. While
      undergoing fMRI, participants imitated own- and other-gender actors performing
      novel, meaningless hand signs; as control conditions, they also simply observed
      such actions and viewed still portraits of the same actors. Only the ventral and
      dorsal striatum, orbitofrontal cortex and amygdala were more active when
      imitating own- compared to other-gender individuals. A Bayesian analysis of the
      BrainMap neuroimaging database demonstrated that the striatal region
      preferentially activated by own-gender imitation is selectively activated by
      classical reward tasks in the literature. Taken together, these findings reveal a
      neurobiological mechanism associated with the own-gender imitation bias and
      demonstrate a novel role of reward-processing neural structures in social
      behavior.

PMID- 22383804
TI  - Neural correlates of focused attention during a brief mindfulness induction.
AB  - Mindfulness meditation-the practice of attending to present moment experience and
      allowing emotions and thoughts to pass without judgment-has shown to be
      beneficial in clinical populations across diverse outcomes. However, the basic
      neural mechanisms by which mindfulness operates and relates to everyday outcomes
      in novices remain unexplored. Focused attention is a common mindfulness induction
      where practitioners focus on specific physical sensations, typically the breath.
      The present study explores the neural mechanisms of this common mindfulness
      induction among novice practitioners. Healthy novice participants completed a
      brief task with both mindful attention [focused breathing (FB)] and control
      (unfocused attention) conditions during functional magnetic resonance imaging
      (fMRI). Relative to the control condition, FB recruited an attention network
      including parietal and prefrontal structures and trait-level mindfulness during
      this comparison also correlated with parietal activation. Results suggest that
      the neural mechanisms of a brief mindfulness induction are related to attention
      processes in novices and that trait mindfulness positively moderates this
      activation.

PMID- 22383806
TI  - Silicon isotope evidence against an enstatite chondrite Earth.
AB  - The compositions of Earth materials are strikingly similar to those of enstatite
      chondrite meteorites in many isotope systems. Although this suggests that Earth
      largely accreted from enstatite chondrites, definitive proof of this model has
      been lacking. By comparing the silicon (Si) isotope signatures of several
      extraterrestrial materials with terrestrial samples, we show that they cannot be
      explained by core-formation scenarios involving a bulk Earth of enstatite
      chondrite composition. Si isotope similarities between the bulk silicate Earth
      and the Moon preclude the existence of a hidden reservoir in the lower mantle, a
      necessary condition of the enstatite chondrite model, and require an equilibrium
      process after the Moon-forming impact. A three-end-member chondritic mixing model
      for Earth reconciles the Si isotope similarities between enstatite chondrites and
      Earth.

PMID- 22383805
TI  - Interleukin-22 drives endogenous thymic regeneration in mice.
AB  - Endogenous thymic regeneration is a crucial function that allows for renewal of
      immune competence after stress, infection, or immunodepletion. However, the
      mechanisms governing this regeneration remain poorly understood. We detail such a
      mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of
      CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were
      increased after thymic insult, and thymic recovery was impaired in IL-22
      deficient mice. IL-22, which signaled through thymic epithelial cells and
      promoted their proliferation and survival, was up-regulated by radio-resistant
      RORgamma(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury
      in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery
      after total body irradiation. These studies reveal mechanisms of endogenous
      thymic repair and offer innovative regenerative strategies for improving immune
      competence.

PMID- 22383807
TI  - Energy capture from thermolytic solutions in microbial reverse-electrodialysis
      cells.
AB  - Reverse electrodialysis allows for the capture of energy from salinity gradients
      between salt and fresh waters, but potential applications are currently limited
      to coastal areas and the need for a large number of membrane pairs. Using salt
      solutions that could be continuously regenerated with waste heat (>=40 degrees C)
      and conventional technologies would allow much wider applications of salinity
      gradient power production. We used reverse electrodialysis ion-exchange membrane
      stacks in microbial reverse-electrodialysis cells to efficiently capture salinity
      gradient energy from ammonium bicarbonate salt solutions. The maximum power
      density using acetate reached 5.6 watts per square meter of cathode surface area,
      which was five times that produced without the dialysis stack, and 3.0 +/- 0.05
      watts per square meter with domestic wastewater. Maximum energy recovery with
      acetate reached 30 +/- 0.5%.

PMID- 22383808
TI  - Crystal structure of human enterovirus 71.
AB  - Enterovirus 71 is a picornavirus associated with fatal neurological illness in
      infants and young children. Here, we report the crystal structure of enterovirus
      71 and show that, unlike in other enteroviruses, the "pocket factor," a small
      molecule that stabilizes the virus, is partly exposed on the floor of the
      "canyon." Thus, the structure of antiviral compounds may require a hydrophilic
      head group designed to interact with residues at the entrance of the pocket.

PMID- 22383809
TI  - Niche and neutral effects of acquired immunity permit coexistence of pneumococcal
      serotypes.
AB  - Over 90 capsular serotypes of Streptococcus pneumoniae, a common nasopharyngeal
      colonizer and major cause of pneumonia, bacteremia, and meningitis, are known. It
      is unclear why some serotypes can persist at all: They are more easily cleared
      from carriage and compete poorly in vivo. Serotype-specific immune responses,
      which could promote diversity in principle, are weak enough to allow repeated
      colonizations by the same type. We show that weak serotype-specific immunity and
      an acquired response not specific to the capsule can together reproduce observed
      diversity. Serotype-specific immunity stabilizes competition, and acquired
      immunity to noncapsular antigens reduces fitness differences. Our model can be
      used to explain the effects of pneumococcal vaccination and indicates general
      factors that regulate the diversity of pathogens.

PMID- 22383815
TI  - Superluminal neutrinos. Loose cable may unravel faster-than-light result.

PMID- 22383810
TI  - The flame challenge.

PMID- 22383816
TI  - Infectious disease. Scientists rush to find clues on new animal virus.

PMID- 22383817
TI  - Reproductive biology. Potential egg stem cells reignite debate.

PMID- 22383819
TI  - Scientific careers. Half-time jobs, full-time scientists.

PMID- 22383818
TI  - Scientific careers. Is motherhood the biggest reason for academia's gender
      imbalance?

PMID- 22383820
TI  - Epidemiology. Overhaul of U.S. child health study concerns investigators.

PMID- 22383821
TI  - Didier Raoult profile. Sound and fury in the microbiology lab.

PMID- 22383822
TI  - Didier Raoult profile. Giant viruses revive old questions about viral origins.

PMID- 22383823
TI  - Animal cognition. 'Killjoys' challenge claims of clever animals.

PMID- 22383824
TI  - Mineral resources. Is the world tottering on the precipice of peak gold?

PMID- 22383826
TI  - Saudi university policy: King Saud response.

PMID- 22383827
TI  - Saudi university policy: King Abdulaziz response.

PMID- 22383828
TI  - Saudi university policy: meaningful cooperation.

PMID- 22383829
TI  - Saudi university policy: overvalued rankings.

PMID- 22383830
TI  - Comment on "Phonemic diversity supports a serial founder effect model of language
      expansion from Africa".
AB  - Atkinson (Reports, 15 April 2011, p. 346) argues that the phonological complexity
      of languages reflects the loss of phonemic distinctions due to successive founder
      events during human migration (the serial founder hypothesis). Statistical
      simulations show that the type I error rate of Atkinson's analysis is hugely
      inflated. The data at best support only a weak interpretation of the serial
      founder hypothesis.

PMID- 22383833
TI  - Conservation. Reconsidering the consequences of selective fisheries.

PMID- 22383834
TI  - Cell biology. Reconfiguring regulation.

PMID- 22383835
TI  - Geophysics. Probing the mantle past.

PMID- 22383836
TI  - Ecology. Facing extinction in real time.

PMID- 22383837
TI  - Chemistry. Roaming reaction pathways along excited states.

PMID- 22383838
TI  - Cell signaling. Structural origins of receptor bias.

PMID- 22383839
TI  - Behavior. Origins of cumulative culture.

PMID- 22383840
TI  - The geological record of ocean acidification.
AB  - Ocean acidification may have severe consequences for marine ecosystems; however,
      assessing its future impact is difficult because laboratory experiments and field
      observations are limited by their reduced ecologic complexity and sample period,
      respectively. In contrast, the geological record contains long-term evidence for
      a variety of global environmental perturbations, including ocean acidification
      plus their associated biotic responses. We review events exhibiting evidence for
      elevated atmospheric CO(2), global warming, and ocean acidification over the past
      ~300 million years of Earth's history, some with contemporaneous extinction or
      evolutionary turnover among marine calcifiers. Although similarities exist, no
      past event perfectly parallels future projections in terms of disrupting the
      balance of ocean carbonate chemistry-a consequence of the unprecedented rapidity
      of CO(2) release currently taking place.

PMID- 22383841
TI  - Turbulence, cleavage, and the naked embryo: a case for coral clones.
AB  - After mass spawning events, coral embryos, lacking the protective capsule of
      other metazoans, are directly exposed to the environment at the ocean surface.
      Here, we present evidence that modest turbulence disrupts the integrity of these
      embryos, which fragment into totipotent cells that develop into proportionately
      smaller functional larvae. The level of turbulence required to fragment coral
      embryos can be generated from small wind-generated waves, which occur frequently
      during coral spawning on the Great Barrier Reef. The formation of planktonic
      coral clones, through natural embryo fragmentation of broadcast spawn, is a
      previously unknown mode of reproduction in the animal kingdom.

PMID- 22383842
TI  - Reactions of solvated electrons initiated by sodium atom ionization at the vacuum
      liquid interface.
AB  - Solvated electrons are powerful reagents in the liquid phase that break chemical
      bonds and thereby create additional reactive species, including hydrogen atoms.
      We explored the distinct chemistry that ensues when electrons are liberated near
      the liquid surface rather than within the bulk. Specifically, we detected the
      products resulting from exposure of liquid glycerol to a beam of sodium atoms.
      The Na atoms ionized in the surface region, generating electrons that reacted
      with deuterated glycerol, C(3)D(5)(OD)(3), to produce D atoms, D(2), D(2)O, and
      glycerol fragments. Surprisingly, 43 +/- 4% of the D atoms traversed the
      interfacial region and desorbed into vacuum before attacking C-D bonds to produce
      D(2).

PMID- 22383843
TI  - No straight path: roaming in both ground- and excited-state photolytic channels
      of NO3 -> NO + O2.
AB  - Roaming mechanisms have recently been observed in several chemical reactions
      alongside trajectories that pass through a traditional transition state. Here, we
      demonstrate that the visible light-induced reaction NO(3) -> NO + O(2) proceeds
      exclusively by roaming. High-level ab initio calculations predict specific NO
      Lambda doublet propensities (orientations of the unpaired electron with respect
      to the molecular rotation plane) for this mechanism, which we discern
      experimentally by ion imaging. The data provide direct evidence for roaming
      pathways in two different electronic states, corresponding to both previously
      documented photolysis channels that produce NO + O(2). More broadly, the results
      raise intriguing questions about the overall prevalence of this unusual reaction
      mechanism.

PMID- 22383844
TI  - High-latitude dust over the North Atlantic: inputs from Icelandic proglacial dust
      storms.
AB  - Mineral aerosols play an important role in the atmosphere-ocean climate system.
      Research has focused almost exclusively on sources in low-latitude arid regions,
      but here we show that there are substantial sources in cold, higher latitudes. A
      6-year record of measurements made on Heimaey, an island south of Iceland,
      reveals frequent dust events with concentrations exceeding 20 micrograms per
      cubic meter. Much of this potentially iron-rich dust is transported southward and
      deposited in the North Atlantic. Emissions are highest in spring and spatially
      and temporally associated with active glacial outwash plains; large dust events
      appear to be associated with glacial outburst floods. In response to global
      warming, ice retreat on Iceland and in other glacierized areas is likely to
      increase dust emissions from these regions.

PMID- 22383845
TI  - Glacial survival of boreal trees in northern Scandinavia.
AB  - It is commonly believed that trees were absent in Scandinavia during the last
      glaciation and first recolonized the Scandinavian Peninsula with the retreat of
      its ice sheet some 9000 years ago. Here, we show the presence of a rare
      mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with
      its highest frequency to the west-an area believed to sustain ice-free refugia
      during most of the last ice age. We further show the survival of DNA from this
      haplotype in lake sediments and pollen of Trondelag in central Norway dating back
      ~10,300 years and chloroplast DNA of pine and spruce in lake sediments adjacent
      to the ice-free Andoya refugium in northwestern Norway as early as ~22,000 and
      17,700 years ago, respectively. Our findings imply that conifer trees survived in
      ice-free refugia of Scandinavia during the last glaciation, challenging current
      views on survival and spread of trees as a response to climate changes.

PMID- 22383846
TI  - Generation of leaf shape through early patterns of growth and tissue polarity.
AB  - A major challenge in biology is to understand how buds comprising a few cells can
      give rise to complex plant and animal appendages like leaves or limbs. We address
      this problem through a combination of time-lapse imaging, clonal analysis, and
      computational modeling. We arrive at a model that shows how leaf shape can arise
      through feedback between early patterns of oriented growth and tissue
      deformation. Experimental tests through partial leaf ablation support this model
      and allow reevaluation of previous experimental studies. Our model allows a range
      of observed leaf shapes to be generated and predicts observed clone patterns in
      different species. Thus, our experimentally validated model may underlie the
      development and evolution of diverse organ shapes.

PMID- 22383847
TI  - Elastic domains regulate growth and organogenesis in the plant shoot apical
      meristem.
AB  - Although genetic control of morphogenesis is well established, elaboration of
      complex shapes requires changes in the mechanical properties of cells. In plants,
      the first visible sign of leaf formation is a bulge on the flank of the shoot
      apical meristem. Bulging results from local relaxation of cell walls, which
      causes them to yield to internal hydrostatic pressure. By manipulation of tissue
      tension in combination with quantitative live imaging and finite-element
      modeling, we found that the slow-growing area at the shoot tip is substantially
      strain-stiffened compared with surrounding fast-growing tissue. We propose that
      strain stiffening limits growth, restricts organ bulging, and contributes to the
      meristem's functional zonation. Thus, mechanical signals are not just passive
      readouts of gene action but feed back on morphogenesis.

PMID- 22383848
TI  - Global network reorganization during dynamic adaptations of Bacillus subtilis
      metabolism.
AB  - Adaptation of cells to environmental changes requires dynamic interactions
      between metabolic and regulatory networks, but studies typically address only one
      or a few layers of regulation. For nutritional shifts between two preferred
      carbon sources of Bacillus subtilis, we combined statistical and model-based data
      analyses of dynamic transcript, protein, and metabolite abundances and promoter
      activities. Adaptation to malate was rapid and primarily controlled
      posttranscriptionally compared with the slow, mainly transcriptionally controlled
      adaptation to glucose that entailed nearly half of the known transcription
      regulation network. Interactions across multiple levels of regulation were
      involved in adaptive changes that could also be achieved by controlling single
      genes. Our analysis suggests that global trade-offs and evolutionary constraints
      provide incentives to favor complex control programs.

PMID- 22383849
TI  - Condition-dependent transcriptome reveals high-level regulatory architecture in
      Bacillus subtilis.
AB  - Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a
      complex manner, the full potential of which has yet to be established for any
      individual bacterial species. Here, we report the transcriptomes of Bacillus
      subtilis exposed to a wide range of environmental and nutritional conditions that
      the organism might encounter in nature. We comprehensively mapped transcription
      units (TUs) and grouped 2935 promoters into regulons controlled by various RNA
      polymerase sigma factors, accounting for ~66% of the observed variance in
      transcriptional activity. This global classification of promoters and detailed
      description of TUs revealed that a large proportion of the detected antisense
      RNAs arose from potentially spurious transcription initiation by alternative
      sigma factors and from imperfect control of transcription termination.

PMID- 22383850
TI  - Catalysis and sulfa drug resistance in dihydropteroate synthase.
AB  - The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme
      in the folate pathway of bacteria and primitive eukaryotes. However, resistance
      mutations have severely compromised the usefulness of these drugs. We report
      structural, computational, and mutagenesis studies on the catalytic and
      resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in
      crystalline DHPS, we have structurally characterized key intermediates along the
      reaction pathway. Results support an S(N)1 reaction mechanism via formation of a
      novel cationic pterin intermediate. We also show that two conserved loops
      generate a substructure during catalysis that creates a specific binding pocket
      for p-aminobenzoic acid, one of the two DHPS substrates. This substructure,
      together with the pterin-binding pocket, explains the roles of the conserved
      active-site residues and reveals how sulfonamide resistance arises.

PMID- 22383852
TI  - The effects of experience and attrition for novice high-school science and
      mathematics teachers.
AB  - Because of the current high proportion of novice high-school teachers, many
      students' mastery of science and mathematics depends on the effectiveness of
      early-career teachers. In this study, which used value-added models to analyze
      high-school teachers' effectiveness in raising test scores on 1.05 million end-of
      course exams, we found that the effectiveness of high-school science and
      mathematics teachers increased substantially with experience but exhibited
      diminishing rates of return by their fourth year; that teachers of algebra 1,
      algebra 2, biology, and physical science who continued to teach for at least 5
      years were more effective as novice teachers than those who left the profession
      earlier; and that novice teachers of physics, chemistry, physical science,
      geometry, and biology exhibited steeper growth in effectiveness than did novice
      non-science, technology, engineering, and mathematics teachers.

PMID- 22383851
TI  - Identification of the social and cognitive processes underlying human cumulative
      culture.
AB  - The remarkable ecological and demographic success of humanity is largely
      attributed to our capacity for cumulative culture, with knowledge and technology
      accumulating over time, yet the social and cognitive capabilities that have
      enabled cumulative culture remain unclear. In a comparative study of sequential
      problem solving, we provided groups of capuchin monkeys, chimpanzees, and
      children with an experimental puzzlebox that could be solved in three stages to
      retrieve rewards of increasing desirability. The success of the children, but not
      of the chimpanzees or capuchins, in reaching higher-level solutions was strongly
      associated with a package of sociocognitive processes-including teaching through
      verbal instruction, imitation, and prosociality-that were observed only in the
      children and covaried with performance.

PMID- 22383853
TI  - Genital malodour in women: an unmet therapeutic challenge.

PMID- 22383854
TI  - Association of type D personality with unhealthy lifestyle, and estimated risk of
      coronary events in the general Icelandic population.
AB  - BACKGROUND: Type D personality is associated with an increased morbidity and
      mortality risk in cardiovascular disease patients, but the mechanisms explaining
      this risk are unclear. We examined whether Type D was associated with coronary
      artery disease (CAD) risk factors, estimated risk of developing CAD, and previous
      cardiac events. DESIGN: Cross-sectional study in the general Icelandic
      population. METHODS: A random sample of 4753 individuals (mean age 49.1 +/- 12.0
      years; 49% men) from the REFINE-Reykjavik study completed assessments for Type D
      personality and conventional CAD risk factors. Ten-year risk of developing CAD
      was estimated with the Icelandic risk calculator. RESULTS: Type D personality
      (22% of sample) was associated with a higher prevalence of hypertension (35 vs.
      31%, p = 0.009), but less use of hypertension medication (58 vs. 65%, p = 0.013)
      in hypertensives, more diabetes (6 vs. 4%, p = 0.023), wider waist circumference
      (p = 0.007), and elevated body mass index (p = 0.025) and blood lipids (p <
      0.05). Type D individuals reported less physical exercise (p = 0.000) and more
      current (26 vs. 21%, p = 0.003) and former smoking (48 vs. 44%, p = 0.036).
      Estimates of 10-year risk of CAD were higher in Type D individuals (12.4%, 95% CI
      1.9 to 23.8%), and Type Ds reported more previous cardiac events than non-Type Ds
      (5 vs. 3%, p < 0.01; OR 1.71, 95% CI 1.21 to 2.42). CONCLUSIONS: In the general
      Icelandic population, Type D personality was associated with differences in
      lifestyle-related CAD risk factors, a higher estimated risk of developing CAD,
      and higher incidence of previous cardiac events. Unhealthy lifestyles may partly
      explain the adverse cardiovascular effect of Type D personality.

PMID- 22383855
TI  - Causes and Consequences of Cognitive Functioning Across the Life Course.
AB  - Research on variation in cognitive abilities has focused largely on their genetic
      or experiential sources and on their economic consequences. This article takes a
      broader look at the consequences of cognitive ability-IQ-across the life course.
      Contrary to received wisdom, the effects of IQ on economic success are almost
      entirely mediated by educational attainment. Among persons with equal levels of
      schooling, IQ has little influence on job performance, occupational standing,
      earnings, or wealth. But there are other, sometimes surprising consequences of IQ
      throughout adult life. The long-term correlates of adolescent cognition include
      drinking behavior, survey participation, Internet use, and the timing of
      menopause. These are surveyed primarily using findings from the Wisconsin
      Longitudinal Study.

PMID- 22383856
TI  - Neighborhood Contexts, Fathers, and Mexican American Young Adolescents'
      Internalizing Symptoms.
AB  - The family stress model posits that contextual stressors, such as neighborhood
      danger, negatively influence youth adjustment, including internalizing symptoms,
      via disruptions in parenting and family processes. The current study examined a
      culturally and contextually modified family stress model in a diverse sample of
      Mexican origin fathers and their children (N = 463) from the Southwestern U.S.
      Results supported the hypothesized negative influence of neighborhood danger on
      youth internalizing symptoms via disruptions in family cohesion. Paternal warmth
      did not play a role in linking contextual stress to outcomes. The role of harsh
      parenting was highly nuanced. Results suggest that both culture and context have
      the potential to moderate putative family stress model associations for specific
      parenting behaviors and further our understanding of the ways that culture and
      context may operate in models of family stress and youth outcomes.

PMID- 22383857
TI  - Integral equations in the study of polar and ionic interaction site fluids.
AB  - In this review article we consider some of the current integral equation
      approaches and application to model polar liquid mixtures. We consider the use of
      multidimensional integral equations and in particular progress on the theory and
      applications of three dimensional integral equations. The IEs we consider may be
      derived from equilibrium statistical mechanical expressions incorporating a
      classical Hamiltonian description of the system. We give example including salt
      solutions, inhomogeneous solutions and systems including proteins and nucleic
      acids.

PMID- 22383858
TI  - Fluoro-substituted ketones from nitriles using acidic and basic reaction
      conditions.
AB  - Fluoro-substituted aliphatic nitriles are shown to undergo the Houben-Hoesch
      reactions with arenes in CF(3)SO(3)H to give fluoro-substituted ketones in good
      yields. The fluorine substituents appear to enhance the reactivities of the
      nitriles (and the nitrilium ion intermediates) compared to similar aliphatic
      nitriles. Fluoro-substituted ketones are also shown to be accessible through the
      reactions of organometallic reagents and fluoro-substituted nitriles.

PMID- 22383859
TI  - Cascade assembly of the benzo[a]anthraquinone ring system common to the
      angucycline antibiotics.
AB  - A benzo[a]anthraquinone ring system, common to a group of angucycline
      antibiotics, has been prepared by a unique cascade of reactions. The reaction
      sequence was initiated by a Suzuki-Miyaura cross-coupling between a bromoquinone
      and vinyl boronic anhdyride. The reaction product is proposed to undergo a 6pi
      electron cyclization triggered by reductive activation of the quinone. The
      reaction process is proposed to be autocatalytic.

PMID- 22383860
TI  - The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening
      Response.
AB  - Associations between early deprivation/neglect in the form of institutional care
      with the cortisol awakening response (CAR) were examined as a function of
      pubertal status among 12- and 13-year-old post-institutionalized youth. CARs
      indexed hypothalamic-pituitary-adrenocortical reactivity. Post-institutionalized
      youth were compared to youth adopted internationally from foster care (adoption
      control) and to nonadopted youth reared in families comparable in parental
      education and income to the adoptive families. Post-institutionalized youth
      exhibited a blunted CAR if they were at earlier but not if they were at later
      stages of puberty. Similarly, for both groups of internationally adopted youth
      combined, earlier but not later stages of puberty were associated with more
      blunted CARs at higher but not lower levels of parent-reported pre-adoption
      physical and social neglect.

PMID- 22383861
TI  - The Impact of Child-Related Stressors on the Psychological Functioning of Lower
      Income Mothers After Hurricane Katrina.
AB  - In the present study, the authors examined the role of child-related stressors in
      the psychological adjustment of lower-income, primarily unmarried and African
      American, mothers (N = 386). All participants lived in areas affected by
      Hurricane Katrina, and about a third were also exposed to Hurricane Rita (30.3%,
      n = 117). Lacking knowledge of a child's safety during the hurricanes was a
      significant predictor of heightened postdisaster psychological distress and
      posttraumatic stress, even after controlling for demographic variables,
      predisaster psychological distress, evacuation timing, and bereavement. From
      interviews with a subset of the participants (n = 57), we found that mothers
      consistently put their own needs behind those of their children. The authors
      recommend policies that promptly reunite mothers with missing children and
      support lower-income mothers in caring for their children during natural
      disasters and the aftermath.

PMID- 22383862
TI  - Relations over Time among Children's Shyness, Emotionality, and Internalizing
      Problems.
AB  - Data regarding children's shyness and emotionality were collected at three time
      points, two years apart (T1: N = 214, M = 6.12 years; T2: N = 185, M = 7.67
      years; T3: N = 185, M = 9.70 years), and internalizing data were collected at T1
      and T3. Relations among parent-rated shyness, emotionality (parent- and teacher
      rated anger, sadness, and positive emotional intensity [EI]), and mother-rated
      internalizing were examined in panel models. In some cases, shyness predicted
      emotionality two years later (teacher-rated anger, parent-rated sadness, teacher
      rated positive EI) and emotionality sometimes predicted shyness two years later
      (teacher-rated sadness, parent-rated positive EI, teacher-rated positive EI).
      Parent-rated shyness and/or emotionality (parent-rated anger and parent-rated
      sadness) predicted internalizing at T3. Results shed light on developmental
      relations between emotionality and shyness, as well as processes of risk for, or
      protection against, the development of internalizing problems.

PMID- 22383863
TI  - Treatment of PTSD in older adults: Do cognitive-behavioral interventions remain
      viable?
AB  - The literature examining trauma among older adults is growing, but little is
      known about the efficacy of empirically supported interventions for PTSD within
      this population. Clinical writing on this topic often implies that cognitive
      behavioral treatments may be ineffective or inappropriate for older adults with
      PTSD given physical and/or cognitive vulnerabilities. Review of the limited
      research in this area, however, provides little support for the claim that
      cognitive-behavioral interventions are ineffective in treating PTSD among the
      elderly. In an effort to explicate specific issues related to treatment process
      and outcome among older survivors of trauma, a case series is presented outlining
      the treatment of three older adults within the context of a structured, cognitive
      behavioral group intervention. Observations from this case series suggests that
      cognitive-behavioral interventions continue to be useful in treating PTSD with
      this population. Specific treatment issues unique to older adults are explored
      and recommendations for future research are discussed.

PMID- 22383864
TI  - A Randomized Controlled Trial Comparing Integrated Cognitive Behavioral Therapy
      Versus Individual Addiction Counseling for Co-occurring Substance Use and
      Posttraumatic Stress Disorders.
AB  - OBJECTIVE: Co-occurring posttraumatic stress (PTSD) and substance use disorders
      provide clinical challenges to addiction treatment providers. Interventions are
      needed that are effective, well-tolerated by patients, and capable of being
      delivered by typical clinicians in community settings. This is a randomized
      controlled trial of integrated cognitive behavioral therapy for co-occurring PTSD
      and substance use disorders.  METHODS: Fifty-three participants sampled from
      seven community addiction treatment programs were randomized to integrated
      cognitive behavioral therapy plus standard care or individual addiction
      counseling plus standard care. Fourteen community therapists employed by these
      programs delivered both manual-guided therapies. Primary outcomes were PTSD
      symptoms, substance use symptoms and therapy retention. Participants were
      assessed at baseline, 3- and 6-month follow-up.  RESULTS: Integrated cognitive
      behavioral therapy was more effective than individual addiction counseling in
      reducing PTSD re-experiencing symptoms and PTSD diagnosis. Individual addiction
      counseling was comparably effective to integrated cognitive behavioral therapy in
      substance use outcomes and on other measures of psychiatric symptom severity.
      Participants assigned to individual addiction counseling with severe PTSD were
      less likely to initiate and engage in the therapy than those assigned to
      integrated cognitive behavioral therapy. In general, participants with severe
      PTSD were more likely to benefit from integrated cognitive behavioral therapy. 
      CONCLUSIONS: The findings support the promise of efficacy of integrated cognitive
      behavioral therapy in improving outcomes for persons in addiction treatment with
      PTSD. Community counselors delivered both interventions with satisfactory
      adherence and competence. Despite several limitations to this research, a larger
      randomized controlled trial of integrated cognitive behavioral therapy appears
      warranted.

PMID- 22383865
TI  - Ten years of pathway analysis: current approaches and outstanding challenges.
AB  - Pathway analysis has become the first choice for gaining insight into the
      underlying biology of differentially expressed genes and proteins, as it reduces
      complexity and has increased explanatory power. We discuss the evolution of
      knowledge base-driven pathway analysis over its first decade, distinctly divided
      into three generations. We also discuss the limitations that are specific to each
      generation, and how they are addressed by successive generations of methods. We
      identify a number of annotation challenges that must be addressed to enable
      development of the next generation of pathway analysis methods. Furthermore, we
      identify a number of methodological challenges that the next generation of
      methods must tackle to take advantage of the technological advances in genomics
      and proteomics in order to improve specificity, sensitivity, and relevance of
      pathway analysis.

PMID- 22383866
TI  - A cell-based computational modeling approach for developing site-directed
      molecular probes.
AB  - Modeling the local absorption and retention patterns of membrane-permeant small
      molecules in a cellular context could facilitate development of site-directed
      chemical agents for bioimaging or therapeutic applications. Here, we present an
      integrative approach to this problem, combining in silico computational models,
      in vitro cell based assays and in vivo biodistribution studies. To target small
      molecule probes to the epithelial cells of the upper airways, a multiscale
      computational model of the lung was first used as a screening tool, in silico.
      Following virtual screening, cell monolayers differentiated on microfabricated
      pore arrays and multilayer cultures of primary human bronchial epithelial cells
      differentiated in an air-liquid interface were used to test the local absorption
      and intracellular retention patterns of selected probes, in vitro. Lastly,
      experiments involving visualization of bioimaging probe distribution in the lungs
      after local and systemic administration were used to test the relevance of
      computational models and cell-based assays, in vivo. The results of in vivo
      experiments were consistent with the results of in silico simulations, indicating
      that mitochondrial accumulation of membrane permeant, hydrophilic cations can be
      used to maximize local exposure and retention, specifically in the upper airways
      after intratracheal administration.

PMID- 22383867
TI  - The efficiency of the human CD8+ T cell response: how should we quantify it, what
      determines it, and does it matter?
AB  - Multidisciplinary techniques, in particular the combination of theoretical and
      experimental immunology, can address questions about human immunity that cannot
      be answered by other means. From the turnover of virus-infected cells in vivo, to
      rates of thymic production and HLA class I epitope prediction, theoretical
      techniques provide a unique insight to supplement experimental approaches. Here
      we present our opinion, with examples, of some of the ways in which mathematics
      has contributed in our field of interest: the efficiency of the human CD8+ T cell
      response to persistent viruses.

PMID- 22383868
TI  - Structural consensus among antibodies defines the antigen binding site.
AB  - The Complementarity Determining Regions (CDRs) of antibodies are assumed to
      account for the antigen recognition and binding and thus to contain also the
      antigen binding site. CDRs are typically discerned by searching for regions that
      are most different, in sequence or in structure, between different antibodies.
      Here, we show that ~20% of the antibody residues that actually bind the antigen
      fall outside the CDRs. However, virtually all antigen binding residues lie in
      regions of structural consensus across antibodies. Furthermore, we show that
      these regions of structural consensus which cover the antigen binding site are
      identifiable from the sequence of the antibody. Analyzing the predicted
      contribution of antigen binding residues to the stability of the antibody-antigen
      complex, we show that residues that fall outside of the traditionally defined
      CDRs are at least as important to antigen binding as residues within the CDRs,
      and in some cases, they are even more important energetically. Furthermore,
      antigen binding residues that fall outside of the structural consensus regions
      but within traditionally defined CDRs show a marginal energetic contribution to
      antigen binding. These findings allow for systematic and comprehensive
      identification of antigen binding sites, which can improve the understanding of
      antigenic interactions and may be useful in antibody engineering and B-cell
      epitope identification.

PMID- 22383869
TI  - Effects of electrical and structural remodeling on atrial fibrillation
      maintenance: a simulation study.
AB  - Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably:
      in patients with long-term atrial fibrillation, fibrillatory episodes are
      typically of increased duration and frequency of occurrence relative to healthy
      controls. This is due to electrical, structural, and contractile remodeling
      processes. We investigated mechanisms of how electrical and structural remodeling
      contribute to perpetuation of simulated atrial fibrillation, using a mathematical
      model of the human atrial action potential incorporated into an anatomically
      realistic three-dimensional structural model of the human atria. Electrical and
      structural remodeling both shortened the atrial wavelength--electrical remodeling
      primarily through a decrease in action potential duration, while structural
      remodeling primarily slowed conduction. The decrease in wavelength correlates
      with an increase in the average duration of atrial fibrillation/flutter episodes.
      The dependence of reentry duration on wavelength was the same for electrical vs.
      structural remodeling. However, the dynamics during atrial reentry varied between
      electrical, structural, and combined electrical and structural remodeling in
      several ways, including: (i) with structural remodeling there were more
      occurrences of fragmented wavefronts and hence more filaments than during
      electrical remodeling; (ii) dominant waves anchored around different anatomical
      obstacles in electrical vs. structural remodeling; (iii) dominant waves were
      often not anchored in combined electrical and structural remodeling. We conclude
      that, in simulated atrial fibrillation, the wavelength dependence of reentry
      duration is similar for electrical and structural remodeling, despite major
      differences in overall dynamics, including maximal number of filaments, wave
      fragmentation, restitution properties, and whether dominant waves are anchored to
      anatomical obstacles or spiralling freely.

PMID- 22383870
TI  - Robust detection of hierarchical communities from Escherichia coli gene
      expression data.
AB  - Determining the functional structure of biological networks is a central goal of
      systems biology. One approach is to analyze gene expression data to infer a
      network of gene interactions on the basis of their correlated responses to
      environmental and genetic perturbations. The inferred network can then be
      analyzed to identify functional communities. However, commonly used algorithms
      can yield unreliable results due to experimental noise, algorithmic
      stochasticity, and the influence of arbitrarily chosen parameter values.
      Furthermore, the results obtained typically provide only a simplistic view of the
      network partitioned into disjoint communities and provide no information of the
      relationship between communities. Here, we present methods to robustly detect co
      regulated and functionally enriched gene communities and demonstrate their
      application and validity for Escherichia coli gene expression data. Applying a
      recently developed community detection algorithm to the network of interactions
      identified with the context likelihood of relatedness (CLR) method, we show that
      a hierarchy of network communities can be identified. These communities
      significantly enrich for gene ontology (GO) terms, consistent with them
      representing biologically meaningful groups. Further, analysis of the most
      significantly enriched communities identified several candidate new regulatory
      interactions. The robustness of our methods is demonstrated by showing that a
      core set of functional communities is reliably found when artificial noise,
      modeling experimental noise, is added to the data. We find that noise mainly acts
      conservatively, increasing the relatedness required for a network link to be
      reliably assigned and decreasing the size of the core communities, rather than
      causing association of genes into new communities.

PMID- 22383871
TI  - Comparison of insertional RNA editing in Myxomycetes.
AB  - RNA editing describes the process in which individual or short stretches of
      nucleotides in a messenger or structural RNA are inserted, deleted, or
      substituted. A high level of RNA editing has been observed in the mitochondrial
      genome of Physarum polycephalum. The most frequent editing type in Physarum is
      the insertion of individual Cs. RNA editing is extremely accurate in Physarum;
      however, little is known about its mechanism. Here, we demonstrate how analyzing
      two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium
      iridis, allows us to test hypotheses about the editing mechanism that can not be
      tested from a single organism alone. First, we show that using the recently
      determined full transcriptome information of Physarum dramatically improves the
      accuracy of computational editing site prediction in Didymium. We use this
      approach to predict genes in the mitochondrial genome of Didymium and identify
      six new edited genes as well as one new gene that appears unedited. Next we
      investigate sequence conservation in the vicinity of editing sites between the
      two organisms in order to identify sites that harbor the information for the
      location of editing sites based on increased conservation. Our results imply that
      the information contained within only nine or ten nucleotides on either side of
      the editing site (a distance previously suggested through experiments) is not
      enough to locate the editing sites. Finally, we show that the codon position bias
      in C insertional RNA editing of these two organisms is correlated with the
      selection pressure on the respective genes thereby directly testing an
      evolutionary theory on the origin of this codon bias. Beyond revealing
      interesting properties of insertional RNA editing in Myxomycetes, our work
      suggests possible approaches to be used when finding sequence motifs for any
      biological process fails.

PMID- 22383873
TI  - Population genetic analyses reveal the African origin and strain variation of
      Cryptococcus neoformans var. grubii.

PMID- 22383874
TI  - Novel transmembrane receptor involved in phagosome transport of lysozymes and
      beta-hexosaminidase in the enteric protozoan Entamoeba histolytica.
AB  - Lysozymes and hexosaminidases are ubiquitous hydrolases in bacteria and
      eukaryotes. In phagocytic lower eukaryotes and professional phagocytes from
      higher eukaryotes, they are involved in the degradation of ingested bacteria in
      phagosomes. In Entamoeba histolytica, which is the intestinal protozoan parasite
      that causes amoebiasis, phagocytosis plays a pivotal role in the nutrient
      acquisition and the evasion from the host defense systems. While the content of
      phagosomes and biochemical and physiological roles of the major phagosomal
      proteins have been established in E. histolytica, the mechanisms of trafficking
      of these phagosomal proteins, in general, remain largely unknown. In this study,
      we identified and characterized for the first time the putative receptor/carrier
      involved in the transport of the above-mentioned hydrolases to phagosomes. We
      have shown that the receptor, designated as cysteine protease binding protein
      family 8 (CPBF8), is localized in lysosomes and mediates transport of lysozymes
      and beta-hexosaminidase alpha-subunit to phagosomes when the amoeba ingests
      mammalian cells or Gram-positive bacillus Clostridium perfringens. We have also
      shown that the binding of CPBF8 to the cargos is mediated by the serine-rich
      domain, more specifically three serine residues of the domain, which likely
      contains trifluoroacetic acid-sensitive O-phosphodiester-linked glycan
      modifications, of CPBF8. We further showed that the repression of CPBF8 by gene
      silencing reduced the lysozyme and beta-hexosaminidase activity in phagosomes and
      delayed the degradation of C. perfringens. Repression of CPBF8 also resulted in
      decrease in the cytopathy against the mammalian cells, suggesting that CPBF8 may
      also be involved in, besides the degradation of ingested bacteria, the
      pathogenesis against the mammalian hosts. This work represents the first case of
      the identification of a transport receptor of hydrolytic enzymes responsible for
      the degradation of microorganisms in phagosomes.

PMID- 22383875
TI  - Transient reversal of episome silencing precedes VP16-dependent transcription
      during reactivation of latent HSV-1 in neurons.
AB  - Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons,
      creating a permanent source of recurrent infections. The latent genome is
      assembled into chromatin and lytic cycle genes are silenced. Processes that
      orchestrate reentry into productive replication (reactivation) remain poorly
      understood. We have used latently infected cultures of primary superior cervical
      ganglion (SCG) sympathetic neurons to profile viral gene expression following a
      defined reactivation stimulus. Lytic genes are transcribed in two distinct
      phases, differing in their reliance on protein synthesis, viral DNA replication
      and the essential initiator protein VP16. The first phase does not require viral
      proteins and has the appearance of a transient, widespread de-repression of the
      previously silent lytic genes. This allows synthesis of viral regulatory proteins
      including VP16, which accumulate in the cytoplasm of the host neuron. During the
      second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly
      cytoplasmic, concentrate in the nucleus where they assemble an activator complex
      on viral promoters. The transactivation function supplied by VP16 promotes
      increased viral lytic gene transcription leading to the onset of genome
      amplification and the production of infectious viral particles. Thus regulated
      localization of de novo synthesized VP16 is likely to be a critical determinant
      of HSV-1 reactivation in sympathetic neurons.

PMID- 22383876
TI  - Nonequivalence of classical MHC class I loci in ability to direct effective
      antiviral immunity.
AB  - Structural diversity in the peptide binding sites of the redundant classical MHC
      antigen presenting molecules is strongly selected in humans and mice. Although
      the encoded antigen presenting molecules overlap in antigen presenting function,
      differences in polymorphism at the MHC I A, B and C loci in humans and higher
      primates indicate these loci are not functionally equivalent. The structural
      basis of these differences is not known. We hypothesize that classical class I
      loci differ in their ability to direct effective immunity against intracellular
      pathogens. Using a picornavirus infection model and chimeric H-2 transgenes, we
      examined locus specific functional determinants distinguishing the ability of
      class I sister genes to direct effective anti viral immunity. Whereas, parental
      FVB and transgenic FVB mice expressing the H-2K(b) gene are highly susceptible to
      persisting Theiler's virus infection within the CNS and subsequent demyelination,
      mice expressing the D(b) transgene clear the virus and are protected from
      demyelination. Remarkably, animals expressing a chimeric transgene, comprised
      primarily of K(b) but encoding the peptide binding domain of D(b), develop a
      robust anti viral CTL response yet fail to clear virus and develop significant
      demyelination. Differences in expression of the chimeric K(b)alpha1alpha2D(b)
      gene (low) and D(b) (high) in the CNS of infected mice mirror expression levels
      of their endogenous H-2(q) counterparts in FVB mice. These findings demonstrate
      that locus specific elements other than those specifying peptide binding and T
      cell receptor interaction can determine ability to clear virus infection. This
      finding provides a basis for understanding locus-specific differences in MHC
      polymorphism, characterized best in human populations.

PMID- 22383877
TI  - ChLae1 and ChVel1 regulate T-toxin production, virulence, oxidative stress
      response, and development of the maize pathogen Cochliobolus heterostrophus.
AB  - LaeA and VeA coordinate secondary metabolism and differentiation in response to
      light signals in Aspergillus spp. Their orthologs, ChLae1 and ChVel1, were
      identified in the maize pathogen Cochliobolus heterostrophus, known to produce a
      wealth of secondary metabolites, including the host selective toxin, T-toxin.
      Produced by race T, T-toxin promotes high virulence to maize carrying Texas male
      sterile cytoplasm (T-cms). T-toxin production is significantly increased in the
      dark in wild type (WT), whereas Chvel1 and Chlae1 mutant toxin levels are much
      reduced in the dark compared to WT. Correspondingly, expression of T-toxin
      biosynthetic genes (Tox1) is up-regulated in the dark in WT, while dark-induced
      expression is much reduced/minimal in Chvel1 and Chlae1 mutants. Toxin production
      and Tox1 gene expression are increased in ChVEL1 overexpression (OE) strains
      grown in the dark and in ChLAE1 strains grown in either light or dark, compared
      to WT. These observations establish ChLae1 and ChVel1 as the first factors known
      to regulate host selective toxin production. Virulence of Chlae1 and Chvel1
      mutants and OE strains is altered on both T-cms and normal cytoplasm maize,
      indicating that both T-toxin mediated super virulence and basic pathogenic
      ability are affected. Deletion of ChLAE1 or ChVEL1 reduces tolerance to H(2)O(2).
      Expression of CAT3, one of the three catalase genes, is reduced in the Chvel1
      mutant. Chlae1 and Chvel1 mutants also show decreased aerial hyphal growth,
      increased asexual sporulation and female sterility. ChLAE1 OE strains are female
      sterile, while ChVEL1 OE strains are more fertile than WT. ChLae1 and ChVel1
      repress expression of 1,8-dihydroxynaphthalene (DHN) melanin biosynthesis genes,
      and, accordingly, melanization is enhanced in Chlae1 and Chvel1 mutants, and
      reduced in OE strains. Thus, ChLae1 and ChVel1 positively regulate T-toxin
      biosynthesis, pathogenicity and super virulence, oxidative stress responses,
      sexual development, and aerial hyphal growth, and negatively control melanin
      biosynthesis and asexual differentiation.

PMID- 22383878
TI  - The invasive capacity of HPV transformed cells requires the hDlg-dependent
      enhancement of SGEF/RhoG activity.
AB  - A major target of the HPV E6 oncoprotein is the human Discs Large (hDlg) tumour
      suppressor, although how this interaction contributes to HPV-induced malignancy
      is still unclear. Using a proteomic approach we show that a strong interacting
      partner of hDlg is the RhoG-specific guanine nucleotide exchange factor SGEF. The
      interaction between hDlg1 and SGEF involves both PDZ and SH3 domain recognition,
      and directly contributes to the regulation of SGEF's cellular localization and
      activity. Consistent with this, hDlg is a strong enhancer of RhoG activity, which
      occurs in an SGEF-dependent manner. We also show that HPV-18 E6 can interact
      indirectly with SGEF in a manner that is dependent upon the presence of hDlg and
      PDZ binding capacity. In HPV transformed cells, E6 maintains a high level of RhoG
      activity, and this is dependent upon the presence of hDlg and SGEF, which are
      found in complex with E6. Furthermore, we show that E6, hDlg and SGEF each
      directly contributes to the invasive capacity of HPV-16 and HPV-18 transformed
      tumour cells. These studies demonstrate that hDlg has a distinct oncogenic
      function in the context of HPV induced malignancy, one of the outcomes of which
      is increased RhoG activity and increased invasive capacity.

PMID- 22383879
TI  - Early priming minimizes the age-related immune compromise of CD8+ T cell
      diversity and function.
AB  - The elderly are particularly susceptible to influenza A virus infections, with
      increased occurrence, disease severity and reduced vaccine efficacy attributed to
      declining immunity. Experimentally, the age-dependent decline in influenza
      specific CD8(+) T cell responsiveness reflects both functional compromise and the
      emergence of 'repertoire holes' arising from the loss of low frequency
      clonotypes. In this study, we asked whether early priming limits the time-related
      attrition of immune competence. Though primary responses in aged mice were
      compromised, animals vaccinated at 6 weeks then challenged >20 months later had T
      cell responses that were normal in magnitude. Both functional quality and the
      persistence of 'preferred' TCR clonotypes that expand in a characteristic
      immunodominance hierarchy were maintained following early priming. Similar to the
      early priming, vaccination at 22 months followed by challenge retained a response
      magnitude equivalent to young mice. However, late priming resulted in reduced
      TCRbeta diversity in comparison with vaccination earlier in life. Thus, early
      priming was critical to maintaining individual and population-wide TCRbeta
      diversity. In summary, early exposure leads to the long-term maintenance of
      memory T cells and thus preserves optimal, influenza-specific CD8(+) T-cell
      responsiveness and protects against the age-related attrition of naive T-cell
      precursors. Our study supports development of vaccines that prime CD8(+) T-cells
      early in life to elicit the broadest possible spectrum of CD8(+) T-cell memory
      and preserve the magnitude, functionality and TCR usage of responding
      populations. In addition, our study provides the most comprehensive analysis of
      the aged (primary, secondary primed-early and secondary primed-late) TCR
      repertoires published to date.

PMID- 22383880
TI  - The Legionella pneumophila effector VipA is an actin nucleator that alters host
      cell organelle trafficking.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, invades and
      replicates within macrophages and protozoan cells inside a vacuole. The type IVB
      Icm/Dot secretion system is necessary for the translocation of effector proteins
      that modulate vesicle trafficking pathways in the host cell, thus avoiding
      phagosome-lysosome fusion. The Legionella VipA effector was previously identified
      by its ability to interfere with organelle trafficking in the Multivesicular Body
      (MVB) pathway when ectopically expressed in yeast. In this study, we show that
      VipA binds actin in vitro and directly polymerizes microfilaments without the
      requirement of additional proteins, displaying properties distinct from other
      bacterial actin nucleators. Microscopy studies revealed that fluorescently tagged
      VipA variants localize to puncta in eukaryotic cells. In yeast these puncta are
      associated with actin-rich regions and components of the Multivesicular Body
      pathway such as endosomes and the MVB-associated protein Bro1. During macrophage
      infection, native translocated VipA associated with actin patches and early
      endosomes. When ectopically expressed in mammalian cells, VipA-GFP displayed a
      similar distribution ruling out the requirement of additional effectors for
      binding to its eukaryotic targets. Interestingly, a mutant form of VipA, VipA-1,
      that does not interfere with organelle trafficking is also defective in actin
      binding as well as association with early endosomes and shows a homogeneous
      cytosolic localization. These results show that the ability of VipA to bind actin
      is related to its association with a specific subcellular location as well as its
      role in modulating organelle trafficking pathways. VipA constitutes a novel type
      of actin nucleator that may contribute to the intracellular lifestyle of
      Legionella by altering cytoskeleton dynamics to target host cell pathways.

PMID- 22383881
TI  - The relative importance of innate immune priming in Wolbachia-mediated dengue
      interference.
AB  - The non-virulent Wolbachia strain wMel and the life-shortening strain wMelPop
      CLA, both originally from Drosophila melanogaster, have been stably introduced
      into the mosquito vector of dengue fever, Aedes aegypti. Each of these Wolbachia
      strains interferes with viral pathogenicity and/or dissemination in both their
      natural Drosophila host and in their new mosquito host, and it has been suggested
      that this virus interference may be due to host immune priming by Wolbachia. In
      order to identify aspects of the mosquito immune response that might underpin
      virus interference, we used whole-genome microarrays to analyse the
      transcriptional response of A. aegypti to the wMel and wMelPop-CLA Wolbachia
      strains. While wMel affected the transcription of far fewer host genes than
      wMelPop-CLA, both strains activated the expression of some immune genes including
      anti-microbial peptides, Toll pathway genes and genes involved in melanization.
      Because the induction of these immune genes might be associated with the very
      recent introduction of Wolbachia into the mosquito, we also examined the same
      Wolbachia strains in their original host D. melanogaster. First we demonstrated
      that when dengue viruses were injected into D. melanogaster, virus accumulation
      was significantly reduced in the presence of Wolbachia, just as in A. aegypti.
      Second, when we carried out transcriptional analyses of the same immune genes up
      regulated in the new heterologous mosquito host in response to Wolbachia we found
      no over-expression of these genes in D. melanogaster, infected with either wMel
      or wMelPop. These results reinforce the idea that the fundamental mechanism
      involved in viral interference in Drosophila and Aedes is not dependent on the up
      regulation of the immune effectors examined, although it cannot be excluded that
      immune priming in the heterologous mosquito host might enhance the virus
      interference trait.

PMID- 22383882
TI  - The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel,
      pyramidal fold.
AB  - Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases,
      are characterized by early suppression of the host innate immune system. One of
      the proteins likely responsible for this effect is VP24. VP24 is known to
      antagonize interferon signaling by binding host karyopherin alpha proteins,
      thereby preventing them from transporting the tyrosine-phosphorylated
      transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1
      directly, suggesting that VP24 can suppress at least two distinct branches of the
      interferon pathway. Here, we also report the first crystal structures of VP24,
      derived from different species of ebolavirus that are pathogenic (Sudan) and
      nonpathogenic to humans (Reston). These structures reveal that VP24 has a novel,
      pyramidal fold. A site on a particular face of the pyramid exhibits reduced
      solvent exchange when in complex with STAT1. This site is above two highly
      conserved pockets in VP24 that contain key residues previously implicated in
      virulence. These crystal structures and accompanying biochemical analysis map
      differences between pathogenic and nonpathogenic viruses, offer templates for
      drug design, and provide the three-dimensional framework necessary for biological
      dissection of the many functions of VP24 in the virus life cycle.

PMID- 22383883
TI  - Depletion of dendritic cells enhances innate anti-bacterial host defense through
      modulation of phagocyte homeostasis.
AB  - Dendritic cells (DCs) as professional antigen-presenting cells play an important
      role in the initiation and modulation of the adaptive immune response. However,
      their role in the innate immune response against bacterial infections is not
      completely defined. Here we have analyzed the role of DCs and their impact on the
      innate anti-bacterial host defense in an experimental infection model of Yersinia
      enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs
      prior to severe infection with Ye. DC depletion significantly increased animal
      survival after Ye infection. The bacterial load in the spleen of DC-depleted mice
      was significantly lower than that of control mice throughout the infection. DC
      depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL
      1alpha, and CCL2 and an increase in the numbers of splenic phagocytes.
      Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial
      killing capacity compared to splenocytes from control mice. Cellular studies
      further showed that this was due to an increased production of reactive oxygen
      species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted
      mice into control mice prior to Ye infection reduced the bacterial load to the
      level of Ye-infected DC-depleted mice, suggesting that the increased number of
      phagocytes with additional ROS production account for the decreased bacterial
      load. Furthermore, after incubation with serum from DC-depleted mice splenocytes
      from control mice increased their bacterial killing capacity, most likely due to
      enhanced ROS production by neutrophils, indicating that serum factors from DC
      depleted mice account for this effect. In summary, we could show that DC
      depletion triggers phagocyte accumulation in the spleen and enhances their anti
      bacterial killing capacity upon bacterial infection.

PMID- 22383884
TI  - A P-loop mutation in Galpha subunits prevents transition to the active state:
      implications for G-protein signaling in fungal pathogenesis.
AB  - Heterotrimeric G-proteins are molecular switches integral to a panoply of
      different physiological responses that many organisms make to environmental cues.
      The switch from inactive to active Galphabetagamma heterotrimer relies on
      nucleotide cycling by the Galpha subunit: exchange of GTP for GDP activates
      Galpha, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP
      and inorganic phosphate, thereby reverting Galpha to its inactive state. In
      several genetic studies of filamentous fungi, such as the rice blast fungus
      Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of Galpha
      subunits is assumed to be GTPase-deficient and thus constitutively active. Here,
      we demonstrate that Galpha(G42R) mutants are not GTPase deficient, but rather
      incapable of achieving the activated conformation. Two crystal structure models
      suggest that Arg-42 prevents a typical switch region conformational change upon
      Galpha(i1)(G42R) binding to GDP.AlF(4)(-) or GTP, but rotameric flexibility at
      this locus allows for unperturbed GTP hydrolysis. Galpha(G42R) mutants do not
      engage the active state-selective peptide KB-1753 nor RGS domains with high
      affinity, but instead favor interaction with Gbetagamma and GoLoco motifs in any
      nucleotide state. The corresponding Galpha(q)(G48R) mutant is not constitutively
      active in cells and responds poorly to aluminum tetrafluoride activation.
      Comparative analyses of M. oryzae strains harboring either G42R or GTPase
      deficient Q/L mutations in the Galpha subunits MagA or MagB illustrate functional
      differences in environmental cue processing and intracellular signaling outcomes
      between these two Galpha mutants, thus demonstrating the in vivo functional
      divergence of G42R and activating G-protein mutants.

PMID- 22383885
TI  - A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male
      gamete development.
AB  - Cell-cycle progression is governed by a series of essential regulatory proteins.
      Two major regulators are cell-division cycle protein 20 (CDC20) and its
      homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting
      complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C
      substrates. The malaria parasite, Plasmodium, is a haploid organism which, during
      its life-cycle undergoes two stages of mitosis; one associated with asexual
      multiplication and the other with male gametogenesis. Cell-cycle regulation and
      DNA replication in Plasmodium was recently shown to be dependent on the activity
      of a number of protein kinases. However, the function of cell division cycle
      proteins that are also involved in this process, such as CDC20 and CDH1 is
      totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent
      malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis
      identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for
      simplicity) suggesting that Plasmodium APC/C has only one regulator. In our
      genetic approach to delete the endogenous cdc20 gene of P. berghei, we
      demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not
      essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis
      in parasite lines with deletions of two kinase genes involved in male sexual
      development (map2 and cdpk4), showed a significant increase in cdc20
      transcription in activated gametocytes. DNA replication and ultra structural
      analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at
      the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and
      sexual stages, but the level of modification was higher in activated gametocytes
      and ookinetes. Changes in global protein phosphorylation patterns in the
      Deltacdc20 mutant parasites were largely different from those observed in the
      Deltamap2 mutant. This suggests that CDC20 and MAP2 are both likely to play
      independent but vital roles in male gametogenesis.

PMID- 22383886
TI  - Characterization of monomeric intermediates during VSV glycoprotein structural
      transition.
AB  - Entry of enveloped viruses requires fusion of viral and cellular membranes,
      driven by conformational changes of viral glycoproteins. Crystal structures
      provide static pictures of pre- and post-fusion conformations of these proteins
      but the transition pathway remains elusive. Here, using several biophysical
      techniques, including analytical ultracentrifugation, circular dichroism,
      electron microscopy and small angle X-ray scattering, we have characterized the
      low-pH-induced fusogenic structural transition of a soluble form of vesicular
      stomatitis virus (VSV) glycoprotein G ectodomain (G(th), aa residues 1-422, the
      fragment that was previously crystallized). While the post-fusion trimer is the
      major species detected at low pH, the pre-fusion trimer is not detected in
      solution. Rather, at high pH, G(th) is a flexible monomer that explores a large
      conformational space. The monomeric population exhibits a marked pH-dependence
      and adopts more elongated conformations when pH decreases. Furthermore, large
      relative movements of domains are detected in absence of significant secondary
      structure modification. Solution studies are complemented by electron micrographs
      of negatively stained viral particles in which monomeric ectodomains of G are
      observed at the viral surface at both pH 7.5 and pH 6.7. We propose that the
      monomers are intermediates during the conformational change and thus that VSV G
      trimers dissociate at the viral surface during the structural transition.

PMID- 22383887
TI  - Cell lineage analysis of the mammalian female germline.
AB  - Fundamental aspects of embryonic and post-natal development, including
      maintenance of the mammalian female germline, are largely unknown. Here we employ
      a retrospective, phylogenetic-based method for reconstructing cell lineage trees
      utilizing somatic mutations accumulated in microsatellites, to study female
      germline dynamics in mice. Reconstructed cell lineage trees can be used to
      estimate lineage relationships between different cell types, as well as cell
      depth (number of cell divisions since the zygote). We show that, in the
      reconstructed mouse cell lineage trees, oocytes form clusters that are separate
      from hematopoietic and mesenchymal stem cells, both in young and old mice,
      indicating that these populations belong to distinct lineages. Furthermore, while
      cumulus cells sampled from different ovarian follicles are distinctly clustered
      on the reconstructed trees, oocytes from the left and right ovaries are not,
      suggesting a mixing of their progenitor pools. We also observed an increase in
      oocyte depth with mouse age, which can be explained either by depth-guided
      selection of oocytes for ovulation or by post-natal renewal. Overall, our study
      sheds light on substantial novel aspects of female germline preservation and
      development.

PMID- 22383888
TI  - A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs
      with neurotoxic activity.
AB  - Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by
      the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally
      extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic
      effects. Here, we provide evidence to support that the mutant HTT CAG repeats
      interfere with cell viability at the RNA level. In human neuronal cells, expanded
      HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete
      penetrance (40 or greater) induced cell death and increased levels of small CAG
      repeated RNAs (sCAGs), of ~21 nucleotides in a Dicer-dependent manner. The
      severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG
      expansion length. Small RNAs obtained from cells expressing mutant HTT and from
      HD human brains significantly decreased neuronal viability, in an Ago2-dependent
      mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently
      blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated
      toxicity. Luciferase-reporter assays showed that expanded HTT silences the
      expression of CTG-containing genes that are down-regulated in HD. These results
      suggest a possible link between HD and sCAG expression with an aberrant
      activation of the siRNA/miRNA gene silencing machinery, which may trigger a
      detrimental response. The identification of the specific cellular processes
      affected by sCAGs may provide insights into the pathogenic mechanisms underlying
      HD, offering opportunities to develop new therapeutic approaches.

PMID- 22383889
TI  - Msx homeobox genes critically regulate embryo implantation by controlling
      paracrine signaling between uterine stroma and epithelium.
AB  - The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors
      that control organogenesis and tissue interactions during embryonic development.
      We observed overlapping expression of these factors in uterine epithelial and
      stromal compartments of pregnant mice prior to embryo implantation. Conditional
      ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due
      to a failure in implantation. In these mutant mice (Msx1/2(d/d)), the uterine
      epithelium exhibited persistent proliferative activity and failed to attach to
      the embryos. Gene expression profiling of uterine epithelium and stroma of
      Msx1/2(d/d) mice revealed an elevated expression of several members of the Wnt
      gene family in the preimplantation uterus. Increased canonical Wnt signaling in
      the stromal cells activated beta-catenin, stimulating the production of a subset
      of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a
      paracrine manner via the FGF receptors in the epithelium to promote epithelial
      proliferation, thereby preventing differentiation of this tissue and creating a
      non-receptive uterus refractory to implantation. Collectively, these findings
      delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which
      operate in the uterus at the time of implantation to control the mesenchymal
      epithelial dialogue critical for successful establishment of pregnancy.

PMID- 22383890
TI  - Developmental transcriptional networks are required to maintain neuronal subtype
      identity in the mature nervous system.
AB  - During neurogenesis, transcription factors combinatorially specify neuronal fates
      and then differentiate subtype identities by inducing subtype-specific gene
      expression profiles. But how is neuronal subtype identity maintained in mature
      neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and
      Tv4), we test whether the subtype transcription factor networks that direct
      differentiation during development are required persistently for long-term
      maintenance of subtype identity. By conditional transcription factor knockdown in
      adult Tv neurons after normal development, we find that most transcription
      factors within the Tv1/Tv4 subtype transcription networks are indeed required to
      maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene
      expression profiles are not simply "locked-in," but must be actively maintained
      by persistent developmental transcription factor networks. We also examined the
      cross-regulatory relationships between all transcription factors that persisted
      in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory
      relationships that had existed between these transcription factors during
      development were no longer present in the mature adult neuron. This points to key
      differences between developmental and maintenance transcriptional regulatory
      networks in individual neurons. Together, our results provide novel insight
      showing that the maintenance of subtype identity is an active process underpinned
      by persistently active, combinatorially-acting, developmental transcription
      factors. These findings have implications for understanding the maintenance of
      all long-lived cell types and the functional degeneration of neurons in the aging
      brain.

PMID- 22383891
TI  - The role of glypicans in Wnt inhibitory factor-1 activity and the structural
      basis of Wif1's effects on Wnt and Hedgehog signaling.
AB  - Proper assignment of cellular fates relies on correct interpretation of Wnt and
      Hedgehog (Hh) signals. Members of the Wnt Inhibitory Factor-1 (WIF1) family are
      secreted modulators of these extracellular signaling pathways. Vertebrate WIF1
      binds Wnts and inhibits their signaling, but its Drosophila melanogaster ortholog
      Shifted (Shf) binds Hh and extends the range of Hh activity in the developing D.
      melanogaster wing. Shf activity is thought to depend on reinforcing interactions
      between Hh and glypican HSPGs. Using zebrafish embryos and the heterologous
      system provided by D. melanogaster wing, we report on the contribution of
      glypican HSPGs to the Wnt-inhibiting activity of zebrafish Wif1 and on the
      protein domains responsible for the differences in Wif1 and Shf specificity. We
      show that Wif1 strengthens interactions between Wnt and glypicans, modulating the
      biphasic action of glypicans towards Wnt inhibition; conversely, glypicans and
      the glypican-binding "EGF-like" domains of Wif1 are required for Wif1's full Wnt
      inhibiting activity. Chimeric constructs between Wif1 and Shf were used to
      investigate their specificities for Wnt and Hh signaling. Full Wnt inhibition
      required the "WIF" domain of Wif1, and the HSPG-binding EGF-like domains of
      either Wif1 or Shf. Full promotion of Hh signaling requires both the EGF-like
      domains of Shf and the WIF domains of either Wif1 or Shf. That the Wif1 WIF
      domain can increase the Hh promoting activity of Shf's EGF domains suggests it is
      capable of interacting with Hh. In fact, full-length Wif1 affected distribution
      and signaling of Hh in D. melanogaster, albeit weakly, suggesting a possible role
      for Wif1 as a modulator of vertebrate Hh signaling.

PMID- 22383892
TI  - Coexpression network analysis in abdominal and gluteal adipose tissue reveals
      regulatory genetic loci for metabolic syndrome and related phenotypes.
AB  - Metabolic Syndrome (MetS) is highly prevalent and has considerable public health
      impact, but its underlying genetic factors remain elusive. To identify gene
      networks involved in MetS, we conducted whole-genome expression and genotype
      profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood
      (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each
      tissue independently identified nine, six, and zero MetS-associated modules of
      coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed
      in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only.
      Differential eigengene network analysis of 8,256 shared probesets detected 22
      shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89),
      seven of which were associated with MetS (FDR P<0.01). The strongest associated
      module, significantly enriched for immune response-related processes, contained
      94/620 (15%) genes with inter-depot differences. In an independent cohort of
      145/141 twins with ABD and WB longitudinal expression data, median variability in
      ABD due to familiality was greater for MetS-associated versus un-associated
      modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8*10(-4)).
      Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter
      depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding
      eSNPs were tested for association with MetS-related phenotypes in two GWAS of
      >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding
      chemerin), was associated with body mass index (BMI) (P = 6.0*10(-4)); and
      rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was
      associated with high-density lipoprotein (P = 8.7*10(-4)) and BMI-adjusted waist
      to-hip ratio (P = 2.4*10(-4)). Since many genes and their interactions influence
      complex traits such as MetS, integrated analysis of genotypes and coexpression
      networks across multiple tissues relevant to clinical traits is an efficient
      strategy to identify novel associations.

PMID- 22383893
TI  - The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits
      Ena/VASP to regulate growth cone dynamics during axon guidance.
AB  - The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and
      axon guidance. However, our understanding of the molecular mechanisms by which
      Eph RTKs regulate these processes is still incomplete. To understand how Eph
      receptors regulate axon guidance in Caenorhabditis elegans, we screened for
      suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We
      identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore,
      VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1
      can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK
      1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of
      the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon
      guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting
      filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK
      1/WSP-1 complex and by inhibiting UNC-34/Ena activity.

PMID- 22383894
TI  - Genome-wide association study identifies chromosome 10q24.32 variants associated
      with arsenic metabolism and toxicity phenotypes in Bangladesh.
AB  - Arsenic contamination of drinking water is a major public health issue in many
      countries, increasing risk for a wide array of diseases, including cancer. There
      is inter-individual variation in arsenic metabolism efficiency and susceptibility
      to arsenic toxicity; however, the basis of this variation is not well understood.
      Here, we have performed the first genome-wide association study (GWAS) of arsenic
      related metabolism and toxicity phenotypes to improve our understanding of the
      mechanisms by which arsenic affects health. Using data on urinary arsenic
      metabolite concentrations and approximately 300,000 genome-wide single nucleotide
      polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we
      identified genome-wide significant association signals (P<5*10(-8)) for
      percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)
      near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic
      variants showing independent associations. In a follow-up analysis of 1,085
      individuals with arsenic-induced premalignant skin lesions (the classical sign of
      arsenic toxicity) and 1,794 controls, we show that one of these five variants
      (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of
      individuals with prospectively measured arsenic (n = 769), we show that rs9527
      interacts with arsenic to influence incident skin lesion risk (P = 0.01).
      Expression quantitative trait locus (eQTL) analyses of genome-wide expression
      data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs
      represent cis-eQTLs for AS3MT (P = 10(-12)) and neighboring gene C10orf32 (P =
      10(-44)), which are involved in C10orf32-AS3MT read-through transcription. This
      is the largest and most comprehensive genomic investigation of arsenic metabolism
      and toxicity to date, the only GWAS of any arsenic-related trait, and the first
      study to implicate 10q24.32 variants in both arsenic metabolism and arsenical
      skin lesion risk. The observed patterns of associations suggest that MMA% and
      DMA% have distinct genetic determinants and support the hypothesis that DMA is
      the less toxic of these two methylated arsenic species. These results have
      potential translational implications for the prevention and treatment of arsenic
      associated toxicities worldwide.

PMID- 22383895
TI  - Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling
      pathway.
AB  - Holoprosencephaly (HPE) is a severe human genetic disease affecting craniofacial
      development, with an incidence of up to 1/250 human conceptions and 1.3 per
      10,000 live births. Mutations in the Sonic Hedgehog (SHH) gene result in HPE in
      humans and mice, and the Shh pathway is targeted by other mutations that cause
      HPE. However, at least 12 loci are associated with HPE in humans, suggesting that
      defects in other pathways contribute to this disease. Although the TGIF1 (TG
      interacting factor) gene maps to the HPE4 locus, and heterozygous loss of
      function TGIF1 mutations are associated with HPE, mouse models have not yet
      explained how loss of Tgif1 causes HPE. Using a conditional Tgif1 allele, we show
      that mouse embryos lacking both Tgif1 and the related Tgif2 have HPE-like
      phenotypes reminiscent of Shh null embryos. Eye and nasal field separation is
      defective, and forebrain patterning is disrupted in embryos lacking both Tgifs.
      Early anterior patterning is relatively normal, but expression of Shh is reduced
      in the forebrain, and Gli3 expression is up-regulated throughout the neural tube.
      Gli3 acts primarily as an antagonist of Shh function, and the introduction of a
      heterozygous Gli3 mutation into embryos lacking both Tgif genes partially rescues
      Shh signaling, nasal field separation, and HPE. Tgif1 and Tgif2 are
      transcriptional repressors that limit Transforming Growth Factor beta/Nodal
      signaling, and we show that reducing Nodal signaling in embryos lacking both
      Tgifs reduces the severity of HPE and partially restores the output of Shh
      signaling. Together, these results support a model in which Tgif function limits
      Nodal signaling to maintain the appropriate output of the Shh pathway in the
      forebrain. These data show for the first time that Tgif1 mutation in mouse
      contributes to HPE pathogenesis and provide evidence that this is due to
      disruption of the Shh pathway.

PMID- 22383896
TI  - Sequestration of highly expressed mRNAs in cytoplasmic granules, P-bodies, and
      stress granules enhances cell viability.
AB  - Transcriptome analyses indicate that a core 10%-15% of the yeast genome is
      modulated by a variety of different stresses. However, not all the induced genes
      undergo translation, and null mutants of many induced genes do not show elevated
      sensitivity to the particular stress. Elucidation of the RNA lifecycle reveals
      accumulation of non-translating mRNAs in cytoplasmic granules, P-bodies, and
      stress granules for future regulation. P-bodies contain enzymes for mRNA
      degradation; under stress conditions mRNAs may be transferred to stress granules
      for storage and return to translation. Protein degradation by the ubiquitin
      proteasome system is elevated by stress; and here we analyzed the steady state
      levels, decay, and subcellular localization of the mRNA of the gene encoding the
      F-box protein, UFO1, that is induced by stress. Using the MS2L mRNA reporter
      system UFO1 mRNA was observed in granules that colocalized with P-bodies and
      stress granules. These P-bodies stored diverse mRNAs. Granules of two mRNAs
      transported prior to translation, ASH1-MS2L and OXA1-MS2L, docked with P-bodies.
      HSP12 mRNA that gave rise to highly elevated protein levels was not observed in
      granules under these stress conditions. ecd3, pat1 double mutants that are
      defective in P-body formation were sensitive to mRNAs expressed ectopically from
      strong promoters. These highly expressed mRNAs showed elevated translation
      compared with wild-type cells, and the viability of the mutants was strongly
      reduced. ecd3, pat1 mutants also exhibited increased sensitivity to different
      stresses. Our interpretation is that sequestration of highly expressed mRNAs in P
      bodies is essential for viability. Storage of mRNAs for future regulation may
      contribute to the discrepancy between the steady state levels of many stress
      induced mRNAs and their proteins. Sorting of mRNAs for future translation or
      decay by individual cells could generate potentially different phenotypes in a
      genetically identical population and enhance its ability to withstand stress.

PMID- 22383897
TI  - Genome-wide association study in east Asians identifies novel susceptibility loci
      for breast cancer.
AB  - Genetic factors play an important role in the etiology of both sporadic and
      familial breast cancer. We aimed to discover novel genetic susceptibility loci
      for breast cancer. We conducted a four-stage genome-wide association study (GWAS)
      in 19,091 cases and 20,606 controls of East-Asian descent including Chinese,
      Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324
      controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852
      controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138
      controls, and finally the top 22 SNPs were investigated in up to 17,423
      additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF
      beta activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent
      association with breast cancer risk across all four stages, with a P-value of
      3.8*10(-12) in the combined analysis of all samples. Adjusted odds ratios (95%
      confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and
      A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P =
      1.9*10(-6) from the combined analysis of all samples), located in intron 5 of the
      ESR1 gene, and SNP rs7107217 (P = 4.6*10(-7)), located at 11q24.3, also showed a
      consistent association in each of the four stages. This study provides strong
      evidence for a novel breast cancer susceptibility locus represented by rs9485372,
      near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci
      located in the ESR1 gene and 11q24.3, respectively.

PMID- 22383898
TI  - Diced triplets expose neurons to RISC.

PMID- 22383899
TI  - Clinical and Pre-clinical Applications of the Transcendental Meditation Program
      in the Prevention and Treatment of Essential Hypertension and Cardiovascular
      Disease in Youth and Adults.
AB  - Acute and chronic environmental and psychosocial stress contributes to the
      pathogenesis and progression of cardiovascular diseases (CVD). Stress reduction
      via Transcendental Meditation (TM)(r) has been shown to lower blood pressure (BP)
      levels and reduce CVD risk in adults and adolescents. This article reviews recent
      findings indicating a beneficial BP-lowering impact of TM in hypertensive adults
      at rest and in pre-hypertensive adolescents at rest, during acute laboratory
      stress and during normal daily activity. These findings have important
      implications for inclusion of TM in efforts to prevent and treat cardiovascular
      diseases and its clinical consequences.

PMID- 22383900
TI  - Network deficiency exacerbates impairment in a mouse model of retinal
      degeneration.
AB  - Neural oscillations play an important role in normal brain activity, but also
      manifest during Parkinson's disease, epilepsy, and other pathological conditions.
      The contribution of these aberrant oscillations to the function of the surviving
      brain remains unclear. In recording from retina in a mouse model of retinal
      degeneration (RD), we found that the incidence of oscillatory activity varied
      across different cell classes, evidence that some retinal networks are more
      affected by functional changes than others. This aberrant activity was driven by
      an independent inhibitory amacrine cell oscillator. By stimulating the surviving
      circuitry at different stages of the neurodegenerative process, we found that
      this dystrophic oscillator further compromises the function of the retina. These
      data reveal that retinal remodeling can exacerbate the visual deficit, and that
      aberrant synaptic activity could be targeted for RD treatment.

PMID- 22383901
TI  - Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats
      with chronic tinnitus: a direct determination using high resolution point
      resolved proton magnetic resonance spectroscopy (H-MRS).
AB  - Damage to the auditory system following high-level sound exposure reduces
      afferent input. Homeostatic mechanisms appear to compensate for the loss.
      Overcompensation may produce the sensation of sound without an objective physical
      correlate, i.e., tinnitus. Several potential compensatory neural processes have
      been identified, such as increased spontaneous activity. The cellular mechanisms
      enabling such compensatory processes may involve down-regulation of inhibitory
      neurotransmission mediated by gamma-amino butyric acid (GABA), and/or up
      regulation of excitatory neurotransmission, mediated by glutamic acid (Glu).
      Because central processing systems are integrated and well-regulated,
      compensatory changes in one system may produce reactive changes in others. Some
      or all may be relevant to tinnitus. To examine the roles of GABA and Glu in
      tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy
      ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus
      (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary
      auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high
      level unilateral exposure to noise, and was measured using a psychophysical
      procedure sensitive to tinnitus. Decreased GABA levels were evident only in the
      MGB, with the greatest decrease, relative to unexposed controls, obtained in the
      contralateral MGB. Small GABA increases may have been present bilaterally in A1
      and in the contralateral DCN. Although Glu levels showed considerable variation,
      Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB
      Glu was increased ipsilaterally but decreased contralaterally. These
      bidirectional and region-specific alterations in GABA and Glu may reflect large
      scale changes in inhibitory and excitatory equilibrium accompanying chronic
      tinnitus. The present results also suggest that targeting both neurotransmitter
      systems may be optimal in developing more effective therapeutics.

PMID- 22383903
TI  - An innovative approach to the study of word learning biases.

PMID- 22383902
TI  - Predictors for rTMS response in chronic tinnitus.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been studied
      as a treatment option for chronic tinnitus for almost 10 years now. Although most
      of these studies have demonstrated beneficial effects, treatment results show
      high interindividual variability and yet, little is known about predictors for
      treatment response. METHODS: Data from 538 patients with chronic tinnitus were
      analyzed. Patients received either low-frequency rTMS over the left temporal
      cortex (n = 345, 1 Hz, 110% motor threshold, 2000 stimuli/day) or combined
      temporal and frontal stimulation (n = 193, 110% motor threshold, 2000 stimuli at
      20 Hz over left dorsolateral prefrontal cortex plus 2000 stimuli at 1 Hz over
      temporal cortex). Numerous demographic, clinical, and audiological variables as
      well as different tinnitus characteristics were analyzed as potential predictors
      for treatment outcome, which was defined as change in the tinnitus questionnaire
      (TQ) score. RESULTS: Both stimulation protocols resulted in a significant
      decrease of TQ scores. Effect sizes were small, however. In the group receiving
      combined treatment, patients with comorbid temporomandibular complaints benefited
      more from rTMS than patients without those complaints. In addition, patients with
      higher TQ scores at baseline had more pronounced TQ reductions than patients with
      low TQ baseline scores. Also, patients who had already improved from screening to
      baseline benefited less than patients without initial improvement. CONCLUSIONS:
      The results from this large sample demonstrate that rTMS shows only small but
      clinically significant effects in the treatment of chronic tinnitus. There are no
      good demographic or clinical predictors for treatment outcome.

PMID- 22383904
TI  - Differential contributions of occipitotemporal regions to person perception.
AB  - Downing and Peelen have produced an excellent review synthesizing the current
      literature on the processing of body stimuli in visual cortex. However, while
      they consider the Extrastriate Body Area (EBA) and Fusiform Body Area (FBA) in
      combination, these regions are physically separate in cortex and must contribute
      differentially to person perception. Here, we evaluate the hierarchical view of
      processing in EBA and FBA and highlight the visual field biases in these regions,
      which may provide insight into their origin and functional roles.

PMID- 22383905
TI  - The development of a myoelectric training tool for above-elbow amputees.
AB  - The objective of above-elbow myoelectric prostheses is to reestablish the
      functionality of missing limbs and increase the quality of life of amputees. By
      using electromyography (EMG) electrodes attached to the surface of the skin,
      amputees are able to control motors in myoelectric prostheses by voluntarily
      contracting the muscles of their residual limb. This work describes the
      development of an inexpensive myoelectric training tool (MTT) designed to help
      upper limb amputees learn how to use myoelectric technology in advance of
      receiving their actual myoelectric prosthesis. The training tool consists of a
      physical and simulated robotic arm, signal acquisition hardware, controller
      software, and a graphical user interface. The MTT improves over earlier training
      systems by allowing a targeted muscle reinnervation (TMR) patient to control up
      to two degrees of freedom simultaneously. The training tool has also been
      designed to function as a research prototype for novel myoelectric controllers. A
      preliminary experiment was performed in order to evaluate the effectiveness of
      the MTT as a learning tool and to identify any issues with the system. Five able
      bodied participants performed a motor-learning task using the EMG controlled
      robotic arm with the goal of moving five balls from one box to another as quickly
      as possible. The results indicate that the subjects improved their skill in
      myoelectric control over the course of the trials. A usability survey was
      administered to the subjects after their trials. Results from the survey showed
      that the shoulder degree of freedom was the most difficult to control.

PMID- 22383906
TI  - Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial
      Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350.
AB  - Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ)
      strain was evaluated as a viral vector to express the ectodomains of fusion
      protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein
      Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The
      glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles
      virus genome and the recombinant viruses were generated. Insertion of the foreign
      gene at the 3(rd) position had a minimal impact on viral replication in vitro.
      RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ
      RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In
      addition, both vaccines also induced insert specific interferon gamma (IFN-gamma)
      secreting T cell response. EZ-RSV F protected cotton rats from pulmonary
      replication of RSV A2 challenge infection. In rhesus macaques, although both EZ
      RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only
      RSV F specific antibody response was detected. Thus, the immunogenicity of the
      foreign antigens delivered by measles vaccine virus is dependent on the nature of
      the insert and the animal models used for vaccine evaluation.

PMID- 22383907
TI  - Severe hypercapnia in critically ill adult cystic fibrosis patients.
AB  - BACKGROUND: Cystic fibrosis (CF) is a monogenetic autosomal recessive multi-organ
      disease affecting approximately 50,000 patients worldwide. Overall median
      survival is continually increasing but pulmonary disease remains the most common
      cause of death. Guidelines have been published in relation to the outpatient
      maintenance of lung health for CF patients and treatment of acute lung
      exacerbations but little information exists about the management of the
      critically ill CF patient. Invasive mechanical ventilation in CF patients with
      acute respiratory failure is associated with poor outcome and high mortality.
      METHODS: Retrospective analysis of adult patients with CF who required
      endotracheal intubation and invasive mechanical ventilation in the Medical
      Intensive Care Unit (MICU). RESULTS: Between the years 2003 - 2009, 14 adult
      patients with CF required endotracheal intubation and invasive mechanical
      ventilation in the Medical Intensive Care Unit (MICU) of the Penn State Milton S.
      Hershey Medical Center, Hershey, Pennsylvania, USA. Eleven patients died in the
      MICU because of progressive respiratory failure and inability to liberate from
      mechanical ventilation. Seven individuals consistently manifested arterial
      partial pressures of carbon dioxide (PaCO(2)) greater than 20.00 kPa despite high
      levels of conventional modes of mechanical ventilation. CONCLUSION: Intubated CF
      patients with respiratory failure have a high mortality rate. Based on our
      experience, multiple factors contribute to severe hypercapnia and the
      effectiveness of conventional modes of mechanical ventilation in many of these
      patients is limited. KEYWORDS: Cystic fibrosis; Mechanical ventilation; Critical
      care; Hypercapnia; Respiratory failure.

PMID- 22383908
TI  - Reappraising the surgical approach on the perforated gastroduodenal ulcer: should
      gastric resection be abandoned?
AB  - BACKGROUND: Advancements in medical care for peptic ulcer disease (PUD) have
      reduced the need for invasive surgical procedures such as gastric resection (GR).
      Community-based PUD studies from a large sampling of PUD patients designed to
      analyze hospital resource use and outcomes after different surgical procedures
      have been rare. We aimed to exhaustively reappraise the risk factors and patient
      demographics that affect PUD patient recoveries after GR compared to those after
      simple closure (SC). METHODS: We used a Japanese administrative database for 6
      consecutive months each year between 2006 and 2010. The database included a total
      of 68,432 PUD patients; we analyzed 6,334 perforation cases and 3,148 cases of
      patients who underwent GR or SC. Study variables were demographics,
      comorbidities, characteristics of PUD, and operative day. Study outcomes that
      were analyzed included mortality, postoperative complications, ventilation
      administration, postoperative blood transfusions, length of stay, total charges,
      operating room (OR) time, and the postoperative fasting period (defined as the
      day of surgery to the day oral food intake was resumed.) To reduce selection bias
      in study procedures and to control the variation in hospital practice, a
      propensity score (PS) matching cohort analysis and a mixed linear regression
      model were used to assess the effects of GR on the outcomes. RESULTS: In 699
      hospitals, 322 GRs and 2,826 SCs were observed. Younger age, duodenal ulcers,
      preexisting anemia and an operative day no more than 24hours were significant
      associated with the choice of SCs. No significant differences were observed in
      study outcomes after either GR or SC; more postoperative blood transfusions and
      longer OR times but shorter postoperative fasting periods were observed after GR.
      Longer OR times, ventilation and postoperative blood transfusion were
      significantly associated with mortality. Not GR but longer OR times use of
      ventilation and complications were the most significant indicators of increased
      resource use. CONCLUSIONS: There were no major significant differences in GR when
      compared to SC with regards to patient recoveries. Surgeons should obtain the
      skills and establish strategies to optimize either type of surgical procedure
      including minimizing OR time and establishing the best perioperative critical
      care. KEYWORDS: Peptic ulcer perforation; Simple closure; Gastric resection;
      Outcome; Resource use.

PMID- 22383909
TI  - Pruritus as reason for encounter in general practice.
AB  - BACKGROUND: Pruritus is a common reason for consulting the general practitioner.
      Data from a primary care setting have seldom been published. The goal of the
      recent investigation was to characterize the consultation prevalence of pruritus,
      frequency of diagnostic and therapeutic procedures, accompanying symptoms and
      results of encounter or diagnoses of patients with pruritus. METHODS: Cross
      sectional data were collected from randomly selected patients during the SESAM 2
      study and compared with unpublished but publicly available data from the Dutch
      Transition Project and the published Australian BEACH study data. RESULTS:
      Overall 64 of the 8,877 patients from the SESAM 2 study consulted a physician for
      pruritus. The male to female ratio was 1.0 : 1.3. Pruritus was more frequent in
      children and people aged over 75 years. Physical examination was performed in all
      patients. Further diagnostic measures were seldom necessary. Drugs were
      prescribed in 84% of the cases. Allergic contact eczema and infectious diseases
      of the skin were the most frequent results of encounter or diagnoses. Medical
      adverse effects and allergic reactions should be considered as causes of
      pruritus. We found no significant association to systemic diseases. CONCLUSIONS:
      In a primary care setting, pruritus occurs regularly. It is associated to
      (infectious) skin diseases. Acute dangerous courses are rare. KEYWORDS: Pruritus;
      Itch; General practice; Primary care; Reason for encounter.

PMID- 22383910
TI  - Effect of serotonin reuptake inhibitors on pulmonary hemodynamics in humans.
AB  - BACKGROUND: Serotonin promotes pulmonary arterial vasoconstriction and pulmonary
      arterial smooth muscle cell proliferation, thereby having the potential to
      increase pulmonary arterial blood pressure. Although serotonin reuptake
      inhibitors (SRIs) might inhibit further deterioration in patients with manifest
      pulmonary arterial hypertension, they may induce pulmonary hypertension in
      healthy newborns after fetal exposure. As it is unclear whether treatment with
      SRIs affects pulmonary hemodynamics in adults without pulmonary hypertension, the
      aim of the present study was to investigate the effect of SRIs on pulmonary
      hemodynamics in such subjects. METHODS: Sixteen patients with stable angina
      pectoris scheduled for first time coronary artery bypass grafting were included
      in the study. Of these 8 were currently treated with an SRI (the SRI group) and 8
      were not (the control group). Pulmonary arterial pressures were measured before
      induction of anesthesia by means of a pulmonary artery catheter. Serotonin
      transporter and 5-HT(2A) receptor gene polymorphisms and platelet 5-HT(2A)
      receptor expression were studied to elucidate their possible role as modifying
      factors. RESULTS: No patients in any of the groups had pulmonary arterial
      hypertension. Mean pulmonary artery pressure was 15.0 mmHg in the SRI group and
      14.5 mmHg in the control group (P = 0.50; 95% confidence interval for the
      difference, -2.9 to +3.9 mmHg). Neither were there any significant differences
      between the groups for any of the other hemodynamic variables studied. The
      various gene polymorphisms and the extent of platelet 5-HT(2A) receptor
      expression did not influence the hemodynamic variables. CONCLUSIONS: SRI
      treatment did not significantly influence pulmonary hemodynamics in patients
      without pulmonary hypertension. KEYWORDS: Serotonin; Selective serotonin reuptake
      inhibitors; Pulmonary hemodynamics; Pulmonary hypertension.

PMID- 22383912
TI  - The association between reactive oxygen metabolites and metabolic syndrome in
      asymptomatic Japanese men.
AB  - BACKGROUND: The association between the oxidative status and metabolic syndrome
      (MetS) should be studied in various populations with various oxidative stress
      related markers. The aim of this cross-sectional study was to investigate the
      association between oxidative status, as assessed by the reactive oxygen
      metabolites (d-ROMs) test, and MetS in asymptomatic Japanese men, in relation to
      age. METHODS: The serum d-ROMs levels were measured in cardiovascular disease
      free, non-smoking, non-medicated males (n = 140), who were divided into groups as
      follows: Group 1, < 60 years (n = 75, mean age 46 +/- 9 [SD] years), and Group 2,
      >= 60 years (n = 65, mean 68 +/- 6 years). The MetS was determined by the NCEP
      ATP recommendations with minor modifications for a Japanese population. RESULTS:
      There was no significant difference in the d-ROMs levels between the subjects
      with and without MetS in Group 2 (>= 60 years), but the subjects with MetS (n =
      38, 324 +/- 59 U. Curr.) exhibited significantly higher d-ROMs levels than those
      without MetS (n = 37, 290 +/- 49 U. Curr., P < 0.01) in Group 1 (< 60 years).
      These differences did not change even after adjustments for basic confounders.
      CONCLUSIONS: These results suggest that oxidative status, as assessed by the d
      ROMs, can be enhanced among asymptomatic younger, but not older, Japanese males
      with MetS. Further studies are required to establish the observed associations.
      KEYWORDS: Oxidative stress; Reactive oxygen species; D-ROMs; Obesity; Metabolic
      syndrome.

PMID- 22383911
TI  - Dyspnea as the reason for encounter in general practice.
AB  - BACKGROUND: Dyspnea is a common reason for consulting a physician. Data from the
      primary care setting on the epidemiology, management, and underlying causes of
      dyspnea have seldomly been published. The present study is aimed to explore the
      consultation prevalence of dyspnea, frequency of diagnostic and therapeutic
      procedures, accompanying symptoms and results of encounter or diagnoses of
      patients with dyspnea in a day-to-day primary care setting. METHODS: Cross
      sectional data were collected from randomly selected patients during the SESAM 2
      study (October 1, 1999 to September 30, 2000). Unpublished but publicly available
      data from the Dutch Transition Project were also analysed. RESULTS: One (n = 93;
      SESAM 2) and 3.9% (n = 7,855; Transition Project) of the patients consulted the
      practioner for dyspnea. The male to female ratio was almost 1 : 1. Half of the
      patients sought medical advice for not previously known dyspnea (Transition
      Project). Dyspnea occurs more frequently among small children (0 to 4 years) and
      elderly adults (> 64 years of age). Nearly all patients received a physical
      examination. Many causes were examined with the help of electrocardiograms but
      spirometry and laboratory tests were also used. Drug prescription was the most
      frequent (79.6%) therapeutic procedure. Acute bronchitis was the most common
      diagnosis. Dyspnea was significantly associated to cough, dysphagia, abnormal
      sputum, airway pain, sweating, and thoracic pain. There was also a significant
      association to chronic obstructive pulmonary disease. CONCLUSIONS: Dyspnea is a
      common reason for seeking medical advice. Emergency cases (e.g. myocardial
      infarction) are rarely present in the general practitioner's consultation. The
      majority of underlying causes are respiratory tract infections and exacerbated,
      previously known chronic diseases. KEYWORDS: Dyspnea; General practice; Primary
      care; Reason for encounter.

PMID- 22383913
TI  - Influence of Physical Activity Intervention on Circulating Soluble Receptor for
      Advanced Glycation end Products in Elderly Subjects.
AB  - BACKGROUND: Inflammation, often accompanied by oxidation, caused by advanced
      glycation end products (AGEs) may be quenched by the soluble receptor for AGEs
      (sRAGE). The present study aimed to investigate the influence of physical
      activity on circulating sRAGE, and the association between changes of circulating
      sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical
      activity intervention study on an elderly subject cohort. METHODS: Serum sRAGE,
      PON1 activity and cardiometabolic variables were measured in 30 community
      dwelling asymptomatic Japanese volunteers (15 men/15 women, mean age 65 years) in
      the pre- and post-phase of a 6-month interventional program designed to increase
      physical activity. RESULTS: The body mass index and sRAGE levels (1103 +/- 496 to
      1030 +/- 437 ng/L, P < 0.05) were significantly reduced during the intervention
      period. In addition, the change of sRAGE was significantly and inversely
      correlated with that of PON1 activity, independent of the other cardiometabolic
      variables (beta = - 0.511, P < 0.01). CONCLUSIONS: This study showed a reduction
      of sRAGE levels, and an inverse correlation between sRAGE and PON1 activity,
      after the intervention study increasing physical activity on an elderly
      population. These findings represent a modest but significant modulation of sRAGE
      by this type of exercise intervention, which warranted future studies on the
      clinical relevance of sRAGE changes in physical activity. KEYWORDS: AGEs; RAGE;
      Paraoxonase1; Exercise; Atherosclerosis.

PMID- 22383914
TI  - Images of cecal volvulus from a strangulating fallopian tube: a case report.
AB  - An unusual case of cecal volvulus arising from a strangulating fallopian tube is
      presented. The etiology, diagnosis, and management guidelines of this infrequent
      cause of large bowel obstruction are reviewed. Computed tomography images are
      included, which demonstrate key features that are pathognomonic for this
      condition. To our knowledge, this is the first report of gynecologic adnexa
      giving rise to cecal volvulus. KEYWORDS: Cecal volvulus; Gynecologic and general
      surgery; Intestinal obstruction.

PMID- 22383915
TI  - A rare cause of dyspnea in a patient presenting to the emergency department: a
      case report and review of the literature of laparoscopic cholecystectomy
      complication.
AB  - In recent years, there has been an emerging preference by patients for emergency
      services due to the efficiency of transactions and the increased quality of
      service. As a result, emergency departments have experienced an extreme density
      of patients. Nevertheless, patients require the same standard of care and should
      be evaluated carefully. The emergency physician should evaluate the patient as a
      whole in light of the findings and not merely according to the recommendations of
      the consultant. We describe in this case report a rare complication occurring
      after laparoscopic cholecystectomy, shortness of breath, which could easily be
      disregarded. KEYWORDS: Laparoscopic cholecystectomy complication; Dyspnea;
      Intrahepatic subcapsular hematoma.

PMID- 22383916
TI  - Severe skew foot deformity in a patient with freeman-sheldon syndrome.
AB  - We report on a 3-year-old boy with the full phenotypic features of Freeman
      Sheldon syndrome (FSS). Severe skew foot deformity has been recognized as
      additional skeletal abnormality. Parents were first degree cousins, raising the
      possibility of autosomal recessive pattern of inheritance. To the best of our
      knowledge this is the first report of severe skew foot deformity in a patient
      with (FSS). KEYWORDS: Freeman-Sheldon syndrome; Skew foot deformity; Metatarsus
      adductus.

PMID- 22383917
TI  - CT Diagnosis of an Abortion-Related Retroperitoneal Space Abscess.
AB  - A female patient with a history of recent abortion was transferred in critically
      ill condition in our hospital. CT imaging on emergency basis depicted an abscess
      in the right retroperitoneal space that included the head of fetus, along with
      rupture of the right lateral wall of uterus. Spiral CT enabled prompt diagnosis
      and therapy of this rare abortion-related complication. KEYWORDS: CT-Spiral;
      Uterus; Complication; Rupture; Obstetrics.

PMID- 22383918
TI  - Rheumatoid arthritis: refractory to infliximab, a tumor necrosis factor
      inhibitor.
AB  - Rheumatoid arthritis is one of the commonest autoimmune diseases. It is a
      chronic, progressive, systemic inflammatory disorder affecting the synovial
      joints and typically producing symmetrical arthritis. If left untreated, it leads
      to joint destruction and thus deformity and disability.In the recent years,
      advances in molecular biology have led to a variety of new treatment approaches
      to rheumatoid arthritis and other systemic inflammatory diseases associated with
      autoimmunity. Anti tumor necrosis factor (TNF) agents are emerging in the
      frontline management of rheumatoid arthritis (RA) in the current era of
      biological treatment. We presented a 46-year-old Chinese female with a history of
      seropositive RA for the past 22 years refractory and intolerant to multiple
      medications including sulphasalazine (SSZ), leflunomide, hydroxychloroquine (HCQ)
      and methotrexate (MTX), thus infliximab, a tumor necrosis factor (TNF) inhibitor
      was initiated. However, despite receiving 6 cycles of infliximab therapy, she
      still complained of persistent disabled multiple joint pain and swelling. This
      report will discuss about rheumatoid arthritis, which is refractory to infliximab
      (a TNF inhibitor) and its alternative. KEYWORDS: Rheumatoid arthritis; Biologics
      treatment; Tumor-necrosis factor inhibitor; Infliximab.

PMID- 22383919
TI  - Multiple systemic infarctions as a complication of bronchial artery embolization
      with polyvinyl alcohol: a case report.
AB  - Bronchial artery embolization (BAE) is a widely used modality of treatment for
      massive hemoptysis which has well known complications such as chest pain, groin
      hematoma and transverse myelitis but systemic embolization of the material used
      in the procedure is very rare and was reported only four times in the literature
      which were all caused by the use of microspheres. Herein we report a case of a 41
      year-old caucasian male who had a history of tuberculosis 10 years ago. He had
      BAE with polyvinyl alcohol (PVA) for the treatment of recurrent hemoptysis. After
      the procedure, the patient complained of severe pain on the left upper quadrant
      and bilateral costovertebral regions and in abdominal CT, multiple infarcts in
      the subcapsular area of the spleen and kidneys were observed. This is the first
      reported case of inadvertent systemic embolization secondary to BAE with PVA.
      Although the risk of systemic embolization is greater with microspheres, still
      potentially serious and life threatening complications may occur with PVA.
      KEYWORDS: Bronchial artery emobolization; Complication; Polyvinyl alcohol.

PMID- 22383920
TI  - Effects of antibiotics on dental implants: a review.
AB  - There are many reasons for dental implant failure, the development of bacteremia
      is concern for dentists. This is due to the possibility of unfavorable result
      such as implant loss or the need for re-treatment. In general, antibiotic
      prophylaxis is recommended for high risk patients such as individuals with an
      immunodeficiency, infectious endocarditis, or previous prosthetic
      instrumentation. However regarding clinically healthy, low and moderate risk
      individuals the use of antibiotics in implant dentistry is controversial. Another
      major concern regarding the over prescription of antibiotics is the selection of
      antibiotic resistant bacteria. A better understanding of the efficacy of
      prophylactic treatments regarding dental implantation is crucial. Thus a
      literature review and comparison of survival rates of dental implants with
      regimens of no, pre or post prophylaxis was performed using systematic literature
      review using reliable electronic databases. Retrospective or prospective
      controlled studies were examined for the influence of preoperative and/or
      postoperative or no antibiosis on dental implant success rate. Of the 11406
      implants used in this literature review, cases with no antibiotics had a 92 %
      success rate, cases with pre-op antibiotic alone had a 96% success rate, cases
      with post-op antibiotic alone had a 97% success rate and cases with both pre and
      post-op antibiotic had a success rate of 96%. Thus, the results from this
      literature review show a > 90% success rate when antibiotics are used compared to
      when they are not used. Thus, no benefit is seen from the use of antibiotic
      prophylaxis in low and moderate risk dental implant patients. KEYWORDS: Dental
      implants; Pre-operative prophylactics; Post-operative prophylactics; Success
      rate.

PMID- 22383921
TI  - Acute respiratory distress syndrome: pathophysiology and therapeutic options.
AB  - Acute Respiratory Distress Syndrome (ARDS) is a common entity in critical care.
      ARDS is associated with many diagnoses, including trauma and sepsis, can lead to
      multiple organ failure and has high mortality. The present article is a narrative
      review of the literature on ARDS, including ARDS pathophysiology and therapeutic
      options currently being evaluated or in use in clinical practice. The literature
      review covers relevant publications until January 2011. Recent developments in
      the therapeutic approach to ARDS include refinements of mechanical ventilatory
      support with emphasis on protective lung ventilation using low tidal volumes,
      increased PEEP with use of recruitment maneuvers to promote reopening of
      collapsed lung alveoli, prone position as rescue therapy for severe hypoxemia,
      and high frequency ventilation. Supportive measures in the management of ARDS
      include attention to fluid balance, restrictive transfusion strategies, and
      minimization of sedatives and neuromuscular blocking agents. Inhaled
      bronchodilators such as inhaled nitric oxide and prostaglandins confer short term
      improvement without proven effect on survival, but are currently used in many
      centers. Use of corticosteroids is also important, and appropriate timely use may
      reduce mortality. Finally, extra corporeal oxygenation methods are very useful as
      rescue therapy in patients with intractable hypoxemia, even though a survival
      benefit has not, to this date been demonstrated. Despite intense ongoing research
      on the pathophysiology and treatment of ARDS, mortality remains high. Many
      pharmacologic and supportive strategies have shown promising results, but data
      from large randomized clinical trials are needed to fully evaluate the true
      effectiveness of these therapies. KEYWORDS: ARDS; Pathophysiology; Treatment.

PMID- 22383922
TI  - Association Between Appendectomy and Clostridium difficile Infection.
AB  - BACKGROUND: Recent theory proposes that the appendix functions as a reservoir for
      commensal bacteria, and serves to re-inoculate the colon with normal flora in the
      event of pathogen exposure or purging of intestinal flora. If true, we reasoned
      that flora from a normal appendix could provide protection against Clostridium
      difficile. We conducted this investigation to examine the protective effect of an
      intact appendix and test the hypothesis that prior appendectomy will be more
      common among patients with a positive test for C. difficile as compared with
      patients who test negative. METHODS: We contacted patients who had undergone C.
      difficile testing and asked them whether or not they had a prior appendectomy.
      Using their responses and results from Toxin A & B EIA tests, we calculated the
      difference in appendectomy rates between those who tested positive for C.
      difficile, and those who tested negative. We considered a positive 15% absolute
      difference to represent a significant increase in appendectomy rate. RESULTS: We
      enrolled 257 patients. Among the 136 who tested positive for C. difficile, 27
      (19.9%) had prior appendectomies, while among 121 patients testing negative for
      C. difficile, 38 (31.4%) had prior appendectomies, yielding a difference in
      appendectomy rates of -11.6% (95% Confidence Interval: -21.6% to -0.9%).
      CONCLUSIONS: The rate of prior appendectomy was actually lower among patients
      with a positive C. difficile test as compared to those with a negative test.
      Conversely, patients who tested positive for C. difficile were more likely to
      have an intact appendix than those who tested negative. These results suggest
      that rather than being protective, an intact appendix appears to promote C.
      difficile acquisition, carriage, and disease. KEYWORDS: Clostridium difficile;
      Appendix; Appendectomy; Microbial reservoir; Infection.

PMID- 22383923
TI  - The importance of cardiac biomarkers on remodelling after myocardial infarction.
AB  - BACKGROUND: The purpose of this study is to evaluate the importance of tenascin-C
      ( TNC), N-terminal pro brain natriuretic peptide (NT-proBNP) and C-reactive
      protein (CRP) on LV remodelling after myocardial infarction (MI). METHODS: Fifty
      seven stable patients with subacute anterior MI who had total or subtotal
      occlusion in the infarct-related left anterior desending artery in coronary
      angiography were enrolled the study. 18 of patients who had total occlusion
      received only medical theraphy, 19 of patients who had total occlusion received
      successful PCI+ medical theraphy and 20 of patients who had subtotal occlusion
      received successful PCI+ medical theraphy. Left ventricular volumes and ejection
      fractions (EF) were measured with echocardiography. Serum TNC, NT-proBNP and CRP
      levels were measured at admission and a month after treatment. RESULTS: There was
      significant increase in LV end-diastolic volume (LVEDV) and LV end-systolic
      volume (LVESV) baseline to follow-up in total-PCI group. Baseline to follow-up; a
      borderline significant increase was observed in LVEDV in the total-medical group.
      No significant difference was seen in LV volumes and EF in the subtotal-PCI
      group. NT-proBNP, TNC and CRP levels were decreased in all groups. The decrease
      in NT-proBNP and CRP values were significant in the total-medical and subtotal
      PCI group but in the total-PCI group they were not significant. The decrease of
      TNC was significant in all groups but the lowest decrease was seen in the total
      PCI group. CONCLUSION: TNC, NT-proBNP and CRP reflect LV remodelling in
      accordance with echocardiography after MI. KEYWORDS: Tenascin-C; NT-pro BNP; CRP;
      Remodelling; Myocardial infarction.

PMID- 22383924
TI  - The extent of blockade following axillary and infraclavicular approaches of
      brachial plexus block in uremic patients.
AB  - INTRODUCTION: This study was aimed to compare the axillary approach performed
      through multiple injection method and vertical infraclavicular approach performed
      through single injection method in terms of the sensory and motor block onset,
      quality, and extent of blocks of brachial plexus in uremic patients who underwent
      arteriovenous fistula surgery. METHODS: Forty patients scheduled for creation of
      arteriovenous fistula with axillary brachial plexus block (group AX, n = 20) or
      infraclavicular brachial plexus block (IC group, n = 20) were examined. The
      median, radial, ulnar, and musculocutaneous nerves were selectively localized by
      nerve stimulation. The volume of the local anesthetics was calculated based on
      the height of each patient, and the volume determined was prepared by mixing 2%
      lidocaine and 0.5% bupivacaine in equal proportions. Sensory and motor block were
      assessed at 3, 6, 9, 12, 15, 18, and 30th min and their durations were measured.
      RESULTS: While the adequate sensory and motor block rate with axillary approach
      was 100% in musculocutaneous, median, radial, ulnar and medial antebrachial
      cutaneous nerves, it was 65% in axillary nerve, 80% in intercostobrachial nerve
      and 95% in medial brachial cutaneous nerve. This rate was found to be 100% for
      all the nerves with infraclavicular approach. CONCLUSION: For arteriovenous
      fistula surgeries in uremic patients, both axillary approach performed through
      multiple injection method and vertical infraclavicular approach performed through
      single injection method can be used successfully; however, for the short
      performance of the procedure, infraclavicular block may be preferred. KEYWORDS:
      Brachial plexus block; Axillary; Infraclavicular; Uremic patients.

PMID- 22383925
TI  - Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe
      Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses.
AB  - BACKGROUND: SEVERE DENGUE DISEASE (SDD) (DHF/DSS: dengue hemorrhagic fever/dengue
      shock syndrome) results from either primary or secondary dengue virus (DENV)
      infections, which occur 4 - 6 days after the onset of fever. As yet, there are no
      definitive clinical or hematological criteria that can specifically identify SDD
      patients during the early acute febrile-phase of disease (day 0 - 3: < 72 hours).
      This study was performed during a SDD (DHF/DSS) epidemic to: 1) identify the DENV
      serotypes that caused SDD during primary or secondary DENV infections; 2)
      identify simple clinical and hematological criteria that could significantly
      discriminate between patients who subsequently developed SDD versus non-SDD (N
      SDD), or had a non-DENV fever of unknown origin (FUO) during day 0 - 3 of fever;
      3) assess whether DENV serotype co-infections resulted in SDD. METHODS: First
      serum samples, with clinical and hematological criteria, were collected from 100
      patients during the early acute febrile-phase (day 0 - 3: < 72 hours), assessed
      for DENV or FUO infections by IgM- and IgG-capture ELISAs on paired serum samples
      and by DENV isolations, and subsequently graded as SDD, N-SDD or FUO patients.
      RESULTS: IN THIS STUDY: 1) Thirty-three patients had DENV infections,
      predominantly secondary DENV-2 infections, including each SDD (DHF/DSS) case; 2)
      Secondary DENV-2/-3 and DENV-2/-4 serotype co-infections however resulted in N
      SDD; 3) Each patient who subsequently developed SDD, but none of the others,
      displayed three clinical criteria: abdominal pain, conjunctival injection and
      veni-puncture bleeding, therefore each of these criteria provided definitively
      significant prognostic (P < 0.001) values; 4) Petechia, positive tourniquet tests
      and hepatomegaly, and neutrophilia or leukopenia also significantly identified
      those who: a) subsequently developed SDD versus N-SDD, or had a FUO; b)
      subsequently developed SDD versus N-SDD; c) subsequently developed N-SDD versus
      FUOs, respectively. CONCLUSIONS: This is the first report of simple definitively
      prognostic criteria for SDD patients, including the first assessment and
      confirmation of conjunctival injection. The three definitive clinical criteria
      used alone, or supported by the other four criteria, could be essential for
      specifically identifying those patients needing prompt hospital-based therapies
      to lessen or avert SDD, without unnecessary hospitalization of the other
      patients. KEYWORDS: Dengue virus; Severe dengue; Dengue fever; Diagnostic;
      Criteria; Hemorrhage; Shock.

PMID- 22383926
TI  - A continuous infusion fascia iliaca compartment block in hip fracture patients: a
      pilot study.
AB  - BACKGROUND: Hip fractures account for 350,000 fractures annually and the
      projected incidence is expected to exceed 6.3 million by 2050. As the number of
      hip fractures continues to increase as a result of the aging American population,
      the importance of limiting and preventing complications is magnified. METHODS:
      This study demonstrated the clinical effects of a continuous fascia iliaca
      compartment block placed pre-operatively when combined with a comprehensive pain
      protocol. All patients who presented to our institution with a hip fracture were
      given the option of having a continuous fascia iliaca compartment block for pain
      control versus usual pain management (non-opioids, opioids, and ice therapy). The
      block was monitored by the pain service until the day of discharge from the
      hospital. Data was collected regarding mean pain scores, average length of stay
      and opioid medication use. RESULTS: There were eighteen males and twenty four
      females. The pain score on post-operative day zero was reduced from a 2010 annual
      average of 4.1 to 1.7 in the pilot study group on the visual analog score. On
      post-operative day one, the 2010 annual average was 2.9 compared to 1.4 in the
      pilot study group. The length of stay was decreased from the 2010 annual average
      of 5.9 days to 4.8 days in the pilot study group. The patients used an average of
      18mg of morphine equivalent medications during the average infusion time of 40.7
      hours. There were no falls or infections noted within our pilot study group.
      CONCLUSIONS: Overall, it has been noticed that the reduction in opioid usage in
      this elderly patient population, with an average age of seventy five years, has
      produced alert and mobile patients often as early as post-operative day one. The
      length of stay has decreased along with the average pain score in the pilot
      sample of forty two patients. KEYWORDS: Hip fracture; Fascia Iliaca Compartment
      Block; Pain Score.

PMID- 22383927
TI  - Endothelial Lipase Plasma Levels are Increased in Patients With Significant
      Carotid Artery Stenosis and History of Neurological Impairment.
AB  - BACKGROUND: Endothelial lipase (EL) is a phospholipase expressed predominantly by
      vascular endothelial cells. The goal of the present study was to examine whether
      EL plasma levels in patients with carotid artery stenosis differ between those
      with previous history of neurological impairment and those without neurological
      symptoms. METHODS: EL plasma levels were measured by a competitive ELISA assay.
      RESULTS: EL plasma levels were significantly higher in the symptomatic, compared
      with the asymptomatic group (mean 489.61 +/- 145 ng/ml (n = 31) vs. 388.39 +/-
      133 ng/ml (n = 24), t-test, P = 0.011). CONCLUSION: We concluded that increased
      EL plasma levels reflect the patients' overall susceptibility for cerebrovascular
      events. KEYWORDS: Atherosclerosis; Carotid artery stenosis; Endothelial lipase;
      Neurological impairment; Carotid endarterectomy.

PMID- 22383928
TI  - Correlation Between High-sensitivity C-reactive Protein and Reactive Oxygen
      Metabolites During A One-year Period Among Asymptomatic Subjects.
AB  - BACKGROUND: Inflammation and oxidative stress are associated with human health
      and the disease status. The present study aimed to investigate the longitudinal
      correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an
      oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP),
      as an inflammatory marker, during a one-year period among asymptomatic subjects.
      METHODS: The data, including anthropometric and biochemical markers, were
      collected at baseline and after the one-year period from 71 participants
      (male/female = 41/30, mean age 50 years). The correlation between the changes of
      the d-ROMs and hsCRP levels during the study period was examined. RESULTS: A
      simple correlation analysis showed a significant and positive correlation to
      exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01).
      This significant correlation remained independent in a multiple linear regression
      analysis adjusted for confounding factors. CONCLUSIONS: The present findings
      suggest that the relationship between the d-ROMs and hsCRP levels could be
      prospectively followed, and that monitoring both markers may help to better
      understand the cooperation of inflammation and oxidative stress in association
      with health and disease. Further studies are necessary to clarify the biological
      mechanism(s) responsible for the observed relationship. KEYWORDS: Oxidative
      stress; Oxygen reactive species; Inflammation; CRP.

PMID- 22383929
TI  - Severe oxalosis with systemic manifestations.
AB  - Ethylene glycol toxicity can have various clinical presentations with different
      organ system involvements. These presentations are independent of the level of
      toxicity. We describe a 31 years old male who presented with ethylene glycol
      toxicity manifesting as anuric renal failure who subsequently developed
      neurological sequela of its toxicity. Ethylene glycol is known to be metabolized
      to various metabolites and is ultimately converted to oxalate which results in
      crystal deposition the renal parenchyma causing renal failure. Oxalate deposition
      can occur in various organs including the nervous system as seen in our patient.
      The majority of patients do not recover from severe oxalosis despite the
      supportive care of hemodialysis in removing the parent compounds. Despite severe
      oxalosis, our patient was fortunate enough to be left with minimal neurological
      sequelae, and eventually was able to cease hemodialysis treatments. KEYWORDS:
      Ethylene glycol; Oxalate; Oxalosis; Glyoxylic acid.

PMID- 22383930
TI  - Subcutaneous sacrococcygeal myxopapillary ependymoma in asian female:a case
      report.
AB  - Subcutaneous sacrococcygeal myxopapillary ependymoma is extremely rare tumor that
      has a tendency to develop in children and adolescents. There have been several
      case reports and sporadic reports in the literature. However, no case has been
      reported in an Asian patient, to the best of our knowledge. We describe a 25-year
      old Asian female patient with a subcutaneous sacrococcygeal myxopapillary
      ependymoma that had been clinically diagnosed as a pilonidal cyst. The tumor was
      treated successfully by surgical excision and the patient is doing well without
      evidence of local recurrence or distant metastasis at 2 years after surgery. 
      KEYWORDS: Myxopapillary ependymoma; Subcutaneous; Sacrococcygeal.

PMID- 22383931
TI  - Tubular adenoma of the breast: a rare presentation and review of the literature.
AB  - Tubular adenomas, also known as pure adenomas, are rare epithelial tumors of the
      breast. Only a few cases have been reported in the literature, especially in
      young women of reproductive age. Postmenopausal women are very rarely affected.
      We describe here a very rare case of tubular breast adenoma in a postmenopausal
      woman who presented with a gradually enlarging breast lump. Clinical examination
      and imaging studies revealed a non-tender well circumscribed left breast tumor
      suggestive of a fibroadenoma. Due to the history of progressive enlargement of
      the breast lump, a surgical excision was performed. Histological findings were
      suggestive of a tubular breast adenoma. We conclude that although tubular breast
      adenoma is rare, it should always be considered in the differential diagnosis in
      postmenopausal patients presenting with a gradually enlarging breast mass.
      Preoperative diagnosis is difficult because tubular adenoma is indistinguishable
      from a fibroadenoma on physical examination and breast imaging. Surgical excision
      is necessary to establish a definitive diagnosis. Clinical presentation and
      management of our patient are discussed along with a review of the literature.
      KEYWORDS: Tubular adenoma; Breast; Breast mass.

PMID- 22383932
TI  - Heparin induced thrombocytopenia: case presentation and review.
AB  - Heparin Induced Thrombocytopenia (HIT) is an adverse effect of heparin therapy
      with possibly devastating consequences. We present a case of HIT Type II. An in
      depth review of HIT is presented, examining the important clinical symptoms and
      diagnostic indicators. The treatment of HIT is then discussed, with an emphasis
      on current therapies. An extensive literature review has been performed to
      present a comprehensive review of the causes, pathophysiology and treatment of
      HIT. KEYWORDS: Heparin induced thrombocytopenia; Anticoagulation; PF4; HIT.

PMID- 22383933
TI  - Troublesome Tuberculosis: A Case Report on Multi-focal Tuberculous Osteomyelitis
      in An Immunocompetent Patient.
AB  - Bone and joint tuberculosis is a chronic debilitating condition that leads to
      progressive damage and even deformity of joints. It may affect one or multiple
      sites. It could present in a myriad of ways which may result in an incorrect
      diagnosis being made. Common misdiagnoses include seronegative inflammatory
      arthritis, septic arthritis, malignancy, osteoporotic fractures and mechanical
      type back pain. It was initially only diagnosed in patients with previous active
      tuberculosis or latent tuberculosis. However, in recent years, it has also been
      reported in patients without a history of previous tuberculosis infection. Making
      a diagnosis of bone and joint tuberculosis is challenging. As the symptoms are
      not always typical, a delay in initiating anti-tuberculosis treatment is not
      uncommon in clinical practice. Systemic features are not always present in multi
      drug resistant tuberculosis of joints which makes the diagnosis even more
      challenging. Multi-drug resistant tuberculosis is an increasingly common problem.
      It is not only limited to immunocompromised patients, but also found in
      immunocompetent patients. Multifocal tuberculous osteomyelitis is an uncommon
      condition and may involve any bone such as the skull, ribs, long bones, spine and
      phalanx. Tuberculous pyomyositis and tuberculous tenosynovitis may also be the
      presenting features of multifocal tuberculosis. Identification of mycobacterium
      tuberculosis in synovial fluid and biopsy, tissue culture, tissue fluid cytology
      and tissue polymerase chain reaction are crucial investigations in these cases.
      As the presentation of extra pulmonary tuberculosis can be very variable, it is
      important to maintain a high index of suspicion. The diagnosis and therefore
      treatment may be expedited using a clinically directed multidisciplinary
      approach. KEYWORDS: Bone and joint tuberculosis; Multi focal tuberculous
      osteomyelitis; Extra-pulmonary tuberculosis; Multi-drug resistant tuberculosis;
      Latent tuberculosis.

PMID- 22383934
TI  - Recurrent syncope as initial symptom in apical intrathoracic tumor.
AB  - Syncope is a common complaint in clinical medical care. The etiology and
      mechanism can be complex. We report two cases experienced recurrent syncope to
      our emergency room without concomitant symptom. The image studies of both cases
      revealed apical neoplasms compress left common carotid artery with mediastinal
      lymphadenopathy and without cardiac/main artery trunk involved. After brain
      lesion, cardiac arrhythmia, and orthostatic hypotension were excluded, syncope
      related to vagus nerve involved was suspected. KEYWORDS: Recurrent syncope;
      Intrathoracic tumor; Neurocardiogenic.

PMID- 22383935
TI  - Cavernous transformation of portal vein secondary to portal vein thrombosis: a
      case report.
AB  - There are few reported cases of cavernous transformation of the portal vein
      (CTPV) in adults. We present a case of a 58 year-old male who was found to have
      this complication due to portal vein thrombosis (PVT). A 58-year old African
      American male with chronic alcohol and tobacco use presented with a 25-day
      history of weakness, generalized malaise, nausea and vomiting associated with
      progressively worsening anorexia and weight loss. The patient was admitted for
      severe anemia in conjunction with abnormal liver function tests and electrolyte
      abnormalities, and to rule out end stage liver disease or hepatic malignancy. The
      work-up for anemia showed no significant colon abnormalities, cholecystitis,
      liver cirrhosis, or liver abnormalities but could not rule out malignancy. An
      esophageogastroduodenoscopy (EGD) was suspicious for a mass compressing the
      stomach and small bowel. After further work-up, the hepatic mass has been
      diagnosed as a cavernous transformation of the portal vein (CTPV), a very rare
      complication of portal vein thrombosis (PVT). Cavernous Transformation of the
      Portal Vein (CTPV) is a rare and incurable complication of portal vein thrombosis
      (PVT) that should be considered as one of the differential diagnoses of a hepatic
      mass. KEYWORDS: Cavernous transformation of the portal vein; Portal vein
      thrombosis; Portal hypertension; Hyperbilirubinemia; Hepatic mass.

PMID- 22383942
TI  - LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in
      C. elegans.
AB  - The small nematode Caenorhabditis elegans displays a spectrum of DNA damage
      responses similar to humans. In order to identify new DNA damage response genes,
      we isolated in a forward genetic screen 14 new mutations conferring
      hypersensitivity to ionizing radiation. We present here our characterization of
      lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain
      and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem
      3(lf) mutants are hypersensitive to various types of DNA damage, including
      ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated
      lem-3 hermaphrodites displayed severe defects during cell division, including
      chromosome mis-segregation and anaphase bridges. The mitotic defects observed in
      irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to
      autointegration factor) mutants. The baf-1 gene codes for an essential and highly
      conserved protein known to interact with the other two C. elegans LEM domain
      proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also
      hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even
      in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM
      domain proteins, plays an important role following DNA damage - possibly by
      promoting the reorganization of damaged chromatin.

PMID- 22383943
TI  - Copy number variations due to large genomic deletion in X-linked chronic
      granulomatous disease.
AB  - Mutations in genes for any of the six subunits of NADPH oxidase cause chronic
      granulomatous disease (CGD), but almost 2/3 of CGD cases are caused by mutations
      in the X-linked CYBB gene, also known as NAD (P) H oxidase 2. Approximately 260
      patients with CGD have been reported in Japan, of whom 92 were shown to have
      mutations of the CYBB gene and 16 to have chromosomal deletions. However, there
      has been very little detailed analysis of the range of the deletion or close
      understanding of the disease based on this. We therefore analyzed genomic
      rearrangements in X-linked CGD using array comparative genomic hybridization
      analysis, revealing the extent and the types of the deletion genes. The subjects
      were five Japanese X-linked CGD patients estimated to have large base deletions
      of 1 kb or more in the CYBB gene (four male patients, one female patient) and the
      mothers of four of those patients. The five Japanese patients were found to range
      from a patient exhibiting deletions only of the CYBB gene to a female patient
      exhibiting an extensive DNA deletion and the DMD and CGD phenotype manifested. Of
      the other three patients, two exhibited CYBB, XK, and DYNLT3 gene deletions. The
      remaining patient exhibited both a deletion encompassing DNA subsequent to the
      CYBB region following intron 2 and the DYNLT3 gene and a complex copy number
      variation involving the insertion of an inverted duplication of a region from the
      centromere side of DYNLT3 into the deleted region.

PMID- 22383944
TI  - Healthy firms: constraints to growth among private health sector facilities in
      Ghana and Kenya.
AB  - BACKGROUND: Health outcomes in developing countries continue to lag the developed
      world, and many countries are not on target to meet the Millennium Development
      Goals. The private health sector provides much of the care in many developing
      countries (e.g., approximately 50 percent in Sub-Saharan Africa), but private
      providers are often poorly integrated into the health system. Efforts to improve
      health systems performance will need to include the private sector and increase
      its contributions to national health goals. However, the literature on
      constraints private health care providers face is limited. METHODOLOGY/PRINCIPAL
      FINDINGS: We analyze data from a survey of private health facilities in Kenya and
      Ghana to evaluate growth constraints facing private providers. A significant
      portion of facilities (Ghana: 62 percent; Kenya: 40 percent) report limited
      access to finance as the most significant barrier they face; only a small
      minority of facilities report using formal credit institutions to finance day to
      day operations (Ghana: 6 percent; Kenya: 11 percent). Other important barriers
      include corruption, crime, limited demand for goods and services, and poor public
      infrastructure. Most facilities have paper-based rather than electronic systems
      for patient records (Ghana: 30 percent; Kenya: 22 percent), accounting (Ghana: 45
      percent; Kenya: 27 percent), and inventory control (Ghana: 41 percent; Kenya: 24
      percent). A majority of clinics in both countries report undertaking activities
      to improve provider skills and to monitor the level and quality of care they
      provide. However, only a minority of pharmacies report undertaking such
      activities. CONCLUSIONS/SIGNIFICANCE: The results suggest that improved access to
      finance and improving business processes especially among pharmacies would
      support improved contributions by private health facilities. These strategies
      might be complementary if providers are more able to take advantage of increased
      access to finance when they have the business processes in place for operating a
      successful business and health facility.

PMID- 22383945
TI  - Impact of Chikungunya virus on Aedes albopictus females and possibility of
      vertical transmission using the actors of the 2007 outbreak in Italy.
AB  - We investigated the impact of CHIKV strains on some Aedes albopictus (Skuse)
      reproductive parameters and the possibility of vertical transmission. Two strains
      were collected in the area where the epidemic occurred in 2007, one isolated from
      mosquitoes, the other one isolated from a viraemic patient. Different types of
      blood meals, either infected or non-infected, were offered to Ae. albopictus
      females, that were then analyzed at increasing time post infection. The virus
      titre, measured by two RT-PCR methods in the blood meals, influenced the rate of
      infection and the rate of dissemination of CHIKV in Ae. albopictus body. We found
      individual variability with respect to the infection/dissemination rates and
      their latency both considering the female's body and appendages. The hatching
      rate was significantly lower for the eggs laid by the infected females than for
      the control eggs, while the mortality during the larval development (from first
      instar larva to adult emergence) was similar among the progeny of infected and
      non-infected female groups. Our findings seem to support the hypothesis that the
      vertical transmission is a rare event under our conditions, and that a certain
      time period is required in order to get the ovarioles infected. Field
      observations conducted during the Spring 2008 showed no evidence of the presence
      of infected overwintering progeny produced by Ae. albopictus females infected
      during the 2007 outbreak.

PMID- 22383947
TI  - Calculating ensemble averaged descriptions of protein rigidity without sampling.
AB  - Previous works have demonstrated that protein rigidity is related to
      thermodynamic stability, especially under conditions that favor formation of
      native structure. Mechanical network rigidity properties of a single conformation
      are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm.
      However, thermodynamic properties require averaging over many samples from the
      ensemble of accessible conformations to accurately account for fluctuations in
      network topology. We have developed a mean field Virtual Pebble Game (VPG) that
      represents the ensemble of networks by a single effective network. That is, all
      possible number of distance constraints (or bars) that can form between a pair of
      rigid bodies is replaced by the average number. The resulting effective network
      is viewed as having weighted edges, where the weight of an edge quantifies its
      capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem
      on this effective network, which eliminates the need to sample. Across a
      nonredundant dataset of 272 protein structures, we apply the VPG to proteins for
      the first time. Our results show numerically and visually that the rigidity
      characterizations of the VPG accurately reflect the ensemble averaged [Formula:
      see text] properties. This result positions the VPG as an efficient alternative
      to understand the mechanical role that chemical interactions play in maintaining
      protein stability.

PMID- 22383948
TI  - Systematic evaluation of the metabolic to mitogenic potency ratio for B10
      substituted insulin analogues.
AB  - BACKGROUND: Insulin analogues comprising acidic amino acid substitutions at
      position B10 have previously been shown to display increased mitogenic potencies
      compared to human insulin and the underlying molecular mechanisms have been
      subject to much scrutiny and debate. However, B10 is still an attractive position
      for amino acid substitutions given its important role in hexamer formation. The
      aim of this study was to investigate the relationships between the receptor
      binding properties as well as the metabolic and mitogenic potencies of a series
      of insulin analogues with different amino acid substitutions at position B10 and
      to identify a B10-substituted insulin analogue without an increased mitogenic to
      metabolic potency ratio. METHODOLOGY/PRINCIPAL FINDINGS: A panel of ten singly
      substituted B10 insulin analogues with different amino acid side chain
      characteristics were prepared and insulin receptor (both isoforms) and IGF-I
      receptor binding affinities using purified receptors, insulin receptor
      dissociation rates using BHK cells over-expressing the human insulin receptor,
      metabolic potencies by lipogenesis in isolated rat adipocytes, and mitogenic
      potencies using two different cell types predominantly expressing either the
      insulin or the IGF-I receptor were systematically investigated. Only analogues
      B10D and B10E with significantly increased insulin and IGF-I receptor affinities
      as well as decreased insulin receptor dissociation rates displayed enhanced
      mitogenic potencies in both cell types employed. For the remaining analogues with
      less pronounced changes in receptor affinities and insulin receptor dissociation
      rates, no apparent correlation between insulin receptor occupancy time and
      mitogenicity was observed. CONCLUSIONS/SIGNIFICANCE: Several B10-substituted
      insulin analogues devoid of disproportionate increases in mitogenic compared to
      metabolic potencies were identified. In the present study, receptor binding
      affinity rather than insulin receptor off-rate appears to be the major
      determinant of both metabolic and mitogenic potency. Our results also suggest
      that the increased mitogenic potency is attributable to both insulin and IGF-I
      receptor activation.

PMID- 22383949
TI  - Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in
      schizophrenia patients: a double-blind, randomized, placebo-controlled trial.
AB  - Glutathione (GSH) dysregulation at the gene, protein, and functional levels has
      been observed in schizophrenia patients. Together with disease-like anomalies in
      GSH deficit experimental models, it suggests that such redox dysregulation can
      play a critical role in altering neural connectivity and synchronization, and
      thus possibly causing schizophrenia symptoms. To determine whether increased GSH
      levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione
      precursor, was administered to patients in a randomized, double-blind, crossover
      protocol for 60 days, followed by placebo for another 60 days (or vice versa). We
      analyzed whole-head topography of the multivariate phase synchronization (MPS)
      for 128-channel resting-state EEGs that were recorded at the onset, at the point
      of crossover, and at the end of the protocol. In this proof of concept study, the
      treatment with NAC significantly increased MPS compared to placebo over the left
      parieto-temporal, the right temporal, and the bilateral prefrontal regions. These
      changes were robust both at the group and at the individual level. Although MPS
      increase was observed in the absence of clinical improvement at a group level, it
      correlated with individual change estimated by Liddle's disorganization scale.
      Therefore, significant changes in EEG synchronization induced by NAC
      administration may precede clinically detectable improvement, highlighting its
      possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01506765.

PMID- 22383950
TI  - Respiratory syncytial virus NS1 protein colocalizes with mitochondrial antiviral
      signaling protein MAVS following infection.
AB  - Respiratory syncytial virus (RSV) nonstructural protein 1(NS1) attenuates type-I
      interferon (IFN) production during RSV infection; however the precise role of RSV
      NS1 protein in orchestrating the early host-virus interaction during infection is
      poorly understood. Since NS1 constitutes the first RSV gene transcribed and the
      production of IFN depends upon RLR (RIG-I-like receptor) signaling, we reasoned
      that NS1 may interfere with this signaling. Herein, we report that NS1 is
      localized to mitochondria and binds to mitochondrial antiviral signaling protein
      (MAVS). Live-cell imaging of rgRSV-infected A549 human epithelial cells showed
      that RSV replication and transcription occurs in proximity to mitochondria. NS1
      localization to mitochondria was directly visualized by confocal microscopy using
      a cell-permeable chemical probe for His(6)-NS1. Further, NS1 colocalization with
      MAVS in A549 cells infected with RSV was shown by confocal laser microscopy and
      immuno-electron microscopy. NS1 protein is present in the mitochondrial fraction
      and co-immunoprecipitates with MAVS in total cell lysatesof A549 cells
      transfected with the plasmid pNS1-Flag. By immunoprecipitation with anti-RIG-I
      antibody, RSV NS1 was shown to associate with MAVS at an early stage of RSV
      infection, and to disrupt MAVS interaction with RIG-I (retinoic acid inducible
      gene) and the downstream IFN antiviral and inflammatory response. Together, these
      results demonstrate that NS1 binds to MAVS and that this binding inhibits the
      MAVS-RIG-I interaction required for IFN production.

PMID- 22383951
TI  - Microallopatry caused strong diversification in Buthus scorpions (Scorpiones:
      Buthidae) in the Atlas Mountains (NW Africa).
AB  - The immense biodiversity of the Atlas Mountains in North Africa might be the
      result of high rates of microallopatry caused by mountain barriers surpassing
      4000 meters leading to patchy habitat distributions. We test the influence of
      geographic structures on the phylogenetic patterns among Buthus scorpions using
      mtDNA sequences. We sampled 91 individuals of the genus Buthus from 51 locations
      scattered around the Atlas Mountains (Antiatlas, High Atlas, Middle Atlas and
      Jebel Sahro). We sequenced 452 bp of the Cytochrome Oxidase I gene which proved
      to be highly variable within and among Buthus species. Our phylogenetic analysis
      yielded 12 distinct genetic groups one of which comprised three subgroups mostly
      in accordance with the orographic structure of the mountain systems. Main clades
      overlap with each other, while subclades are distributed parapatrically.
      Geographic structures likely acted as long-term barriers among populations
      causing restriction of gene flow and allowing for strong genetic differentiation.
      Thus, genetic structure and geographical distribution of genetic (sub)clusters
      follow the classical theory of allopatric differentiation where distinct groups
      evolve without range overlap until reproductive isolation and ecological
      differentiation has built up. Philopatry and low dispersal ability of Buthus
      scorpions are the likely causes for the observed strong genetic differentiation
      at this small geographic scale.

PMID- 22383946
TI  - Children who acquire HIV infection perinatally are at higher risk of early death
      than those acquiring infection through breastmilk: a meta-analysis.
AB  - BACKGROUND: Assumptions about survival of HIV-infected children in Africa without
      antiretroviral therapy need to be updated to inform ongoing UNAIDS modelling of
      paediatric HIV epidemics among children. Improved estimates of infant survival by
      timing of HIV-infection (perinatally or postnatally) are thus needed.
      METHODOLOGY/PRINCIPAL FINDINGS: A pooled analysis was conducted of individual
      data of all available intervention cohorts and randomized trials on prevention of
      HIV mother-to-child transmission in Africa. Studies were right-censored at the
      time of infant antiretroviral initiation. Overall mortality rate per 1000 child
      years of follow-up was calculated by selected maternal and infant
      characteristics. The Kaplan-Meier method was used to estimate survival curves by
      child's HIV infection status and timing of HIV infection. Individual data from 12
      studies were pooled, with 12,112 children of HIV-infected women. Mortality rates
      per 1,000 child-years follow-up were 39.3 and 381.6 for HIV-uninfected and
      infected children respectively. One year after acquisition of HIV infection, an
      estimated 26% postnatally and 52% perinatally infected children would have died;
      and 4% uninfected children by age 1 year. Mortality was independently associated
      with maternal death (adjusted hazard ratio 2.2, 95%CI 1.6-3.0), maternal CD4<350
      cells/ml (1.4, 1.1-1.7), postnatal (3.1, 2.1-4.1) or peri-partum HIV-infection
      (12.4, 10.1-15.3). CONCLUSIONS/RESULTS: These results update previous work and
      inform future UNAIDS modelling by providing survival estimates for HIV-infected
      untreated African children by timing of infection. We highlight the urgent need
      for the prevention of peri-partum and postnatal transmission and timely
      assessment of HIV infection in infants to initiate antiretroviral care and
      support for HIV-infected children.

PMID- 22383952
TI  - Transcriptional regulation of N-acetylglutamate synthase.
AB  - The urea cycle converts toxic ammonia to urea within the liver of mammals. At
      least 6 enzymes are required for ureagenesis, which correlates with dietary
      protein intake. The transcription of urea cycle genes is, at least in part,
      regulated by glucocorticoid and glucagon hormone signaling pathways. N
      acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate
      (NAG), that is essential for the catalytic function of the first and rate
      limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However,
      despite the important role of NAGS in ammonia removal, little is known about the
      mechanisms of its regulation. We identified two regions of high conservation
      upstream of the translation start of the NAGS gene. Reporter assays confirmed
      that these regions represent promoter and enhancer and that the enhancer is
      tissue specific. Within the promoter, we identified multiple transcription start
      sites that differed between liver and small intestine. Several transcription
      factor binding motifs were conserved within the promoter and enhancer regions
      while a TATA-box motif was absent. DNA-protein pull-down assays and chromatin
      immunoprecipitation confirmed binding of Sp1 and CREB, but not C/EBP in the
      promoter and HNF-1 and NF-Y, but not SMAD3 or AP-2 in the enhancer. The
      functional importance of these motifs was demonstrated by decreased transcription
      of reporter constructs following mutagenesis of each motif. The presented data
      strongly suggest that Sp1, CREB, HNF-1, and NF-Y, that are known to be responsive
      to hormones and diet, regulate NAGS transcription. This provides molecular
      mechanism of regulation of ureagenesis in response to hormonal and dietary
      changes.

PMID- 22383953
TI  - Immunization of mice with recombinant protein CobB or AsnC confers protection
      against Brucella abortus infection.
AB  - Due to drawbacks of live attenuated vaccines, much more attention has been
      focused on screening of Brucella protective antigens as subunit vaccine
      candidates. Brucella is a facultative intracellular bacterium and cell mediated
      immunity plays essential roles for protection against Brucella infection.
      Identification of Brucella antigens that present T-cell epitopes to the host
      could enable development of such vaccines. In this study, 45 proven or putative
      pathogenesis-associated factors of Brucella were selected according to currently
      available data. After expressed and purified, 35 proteins were qualified for
      analysis of their abilities to stimulate T-cell responses in vitro. Then, an in
      vitro gamma interferon (IFN-gamma) assay was used to identify potential T-cell
      antigens from B. abortus. In total, 7 individual proteins that stimulated strong
      IFN-gamma responses in splenocytes from mice immunized with B. abortus live
      vaccine S19 were identified. The protective efficiencies of these 7 recombinant
      proteins were further evaluated. Mice given BAB1_1316 (CobB) or BAB1_1688 (AsnC)
      plus adjuvant could provide protection against virulent B. abortus infection,
      similarly with the known protective antigen Cu-Zn SOD and the license vaccine
      S19. In addition, CobB and AsnC could induce strong antibodies responses in
      BALB/c mice. Altogether, the present study showed that CobB or AsnC protein could
      be useful antigen candidates for the development of subunit vaccines against
      brucellosis with adequate immunogenicity and protection efficacy.

PMID- 22383954
TI  - A nonluminescent and highly virulent Vibrio harveyi strain is associated with
      "bacterial white tail disease" of Litopenaeus vannamei shrimp.
AB  - Recurrent outbreaks of a disease in pond-cultured juvenile and subadult
      Litopenaeus vannamei shrimp in several districts in China remain an important
      problem in recent years. The disease was characterized by "white tail" and
      generally accompanied by mass mortalities. Based on data from the microscopical
      analyses, PCR detection and 16S rRNA sequencing, a new Vibrio harveyi strain
      (designated as strain HLB0905) was identified as the etiologic pathogen. The
      bacterial isolation and challenge tests demonstrated that the HLB0905 strain was
      nonluminescent but highly virulent. It could cause mass mortality in affected
      shrimp during a short time period with a low dose of infection. Meanwhile, the
      histopathological and electron microscopical analysis both showed that the
      HLB0905 strain could cause severe fiber cell damages and striated muscle necrosis
      by accumulating in the tail muscle of L. vannamei shrimp, which led the affected
      shrimp to exhibit white or opaque lesions in the tail. The typical sign was
      closely similar to that caused by infectious myonecrosis (IMN), white tail
      disease (WTD) or penaeid white tail disease (PWTD). To differentiate from such
      diseases as with a sign of "white tail" but of non-bacterial origin, the present
      disease was named as "bacterial white tail disease (BWTD)". Present study
      revealed that, just like IMN and WTD, BWTD could also cause mass mortalities in
      pond-cultured shrimp. These results suggested that some bacterial strains are
      changing themselves from secondary to primary pathogens by enhancing their
      virulence in current shrimp aquaculture system.

PMID- 22383955
TI  - Simukunin from the salivary glands of the black fly Simulium vittatum inhibits
      enzymes that regulate clotting and inflammatory responses.
AB  - BACKGROUND: Black flies (Diptera: Simuliidae) feed on blood, and are important
      vectors of Onchocerca volvulus, the etiolytic agent of River Blindness. Blood
      feeding depends on pharmacological properties of saliva, including
      anticoagulation, but the molecules responsible for this activity have not been
      well characterized. METHODOLOGY/PRINCIPAL FINDINGS: Two Kunitz family proteins,
      SV-66 and SV-170, were identified in the sialome of the black fly Simulium
      vittatum. As Kunitz proteins are inhibitors of serine proteases, we hypothesized
      that SV-66 and/or -170 were involved in the anticoagulant activity of black fly
      saliva. Our results indicated that recombinant (r) SV-66 but not rSV-170
      inhibited plasma coagulation. Mutational analysis suggested that SV-66 is a
      canonical BPTI-like inhibitor. Functional assays indicated that rSV66 reduced the
      activity of ten serine proteases, including several involved in mammalian
      coagulation. rSV-66 most strongly inhibited the activity of Factor Xa, elastase,
      and cathepsin G, exhibited lesser inhibitory activity against Factor IXa, Factor
      XIa, and plasmin, and exhibited no activity against Factor XIIa and thrombin.
      Surface plasmon resonance studies indicated that rSV-66 bound with highest
      affinity to elastase (K(D) = 0.4 nM) and to the active site of FXa (K(D) = 3.07
      nM). We propose the name "Simukunin" for this novel protein. CONCLUSIONS: We
      conclude that Simukunin preferentially inhibits Factor Xa. The inhibition of
      elastase and cathepsin G further suggests this protein may modulate inflammation,
      which could potentially affect pathogen transmission.

PMID- 22383956
TI  - Delayed cutaneous wound healing and aberrant expression of hair follicle stem
      cell markers in mice selectively lacking Ctip2 in epidermis.
AB  - BACKGROUND: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an
      important regulator of skin homeostasis, and is overexpressed in head and neck
      cancer. Ctip2(ep-/-) mice, selectively ablated for Ctip2 in epidermal
      keratinocytes, exhibited impaired terminal differentiation and delayed epidermal
      permeability barrier (EPB) establishment during development, similar to what was
      observed in Ctip2 null (Ctip2(-/-)) mice. Considering that as an important role
      of Ctip2, and the fact that molecular networks which underlie cancer progression
      partially overlap with those responsible for tissue remodeling, we sought to
      determine the role of Ctip2 during cutaneous wound healing. METHODOLOGY/PRINCIPAL
      FINDINGS: Full thickness excisional wound healing experiments were performed on
      Ctip2(L2/L2) and Ctip2(ep-/-) animals per time point and used for harvesting
      samples for histology, immunohistochemistry (IHC) and immunoblotting. Results
      demonstrated inherent defects in proliferation and migration of Ctip2 lacking
      keratinocytes during re-epithelialization. Mutant mice exhibited reduced
      epidermal proliferation, delayed keratinocyte activation, altered cell-cell
      adhesion and impaired ECM development. Post wounding, Ctip2(ep-/-) mice wounds
      displayed lack of E-Cadherin suppression in the migratory tongue, insufficient
      expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust
      induction of K8. Importantly, dysregulated expression of several hair follicle
      (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in
      mutant skin during wound repair. CONCLUSIONS/SIGNIFICANCE: Results confirm a cell
      autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation
      and/or differentiation, and to maintain HF stem cells during cutaneous wounding.
      Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue
      formation and tissue contraction during wound closure.

PMID- 22383957
TI  - F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread
      throughout the actinomycetales.
AB  - Two classes of F(420)-dependent reductases (FDR-A and FDR-B) that can reduce
      aflatoxins and thereby degrade them have previously been isolated from
      Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more
      activity than the other. F(420) is a cofactor with a low reduction potential that
      is largely confined to the Actinomycetales and some Archaea and Proteobacteria.
      We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales,
      finding that nine can also use F(420)H(2) to reduce aflatoxin. Thus FDR-As may be
      responsible for the previously observed degradation of aflatoxin in other
      Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin
      belonged to a distinct clade (herein denoted FDR-AA), and our subsequent
      expression and analysis of seven other FDR-AAs from M. smegmatis found that none
      could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce
      aflatoxin also showed activity with coumarin and three furanocoumarins
      (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested
      showed any of these activities. The shared feature of the compounds that were
      substrates was an alpha,beta-unsaturated lactone moiety. This moiety occurs in a
      wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As
      and FDR-Bs may have evolved to harness the reducing power of F(420) to metabolise
      such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction
      of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to
      multiple products.

PMID- 22383958
TI  - Molecular characterization of clinical isolates of Aeromonas species from
      Malaysia.
AB  - BACKGROUND: Aeromonas species are common inhabitants of aquatic environments
      giving rise to infections in both fish and humans. Identification of aeromonads
      to the species level is problematic and complex due to their phenotypic and
      genotypic heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: Aeromonas hydrophila or
      Aeromonas sp were genetically re-identified using a combination of previously
      published methods targeting GCAT, 16S rDNA and rpoD genes. Characterization based
      on the genus specific GCAT-PCR showed that 94 (96%) of the 98 strains belonged to
      the genus Aeromonas. Considering the patterns obtained for the 94 isolates with
      the 16S rDNA-RFLP identification method, 3 clusters were recognised, i.e. A.
      caviae (61%), A. hydrophila (17%) and an unknown group (22%) with atypical RFLP
      restriction patterns. However, the phylogenetic tree constructed with the
      obtained rpoD sequences showed that 47 strains (50%) clustered with the sequence
      of the type strain of A. aquariorum, 18 (19%) with A. caviae, 16 (17%) with A.
      hydrophila, 12 (13%) with A. veronii and one strain (1%) with the type strain of
      A. trota. PCR investigation revealed the presence of 10 virulence genes in the 94
      isolates as: lip (91%), exu (87%), ela (86%), alt (79%), ser (77%), fla (74%),
      aer (72%), act (43%), aexT (24%) and ast (23%). CONCLUSIONS/SIGNIFICANCE: This
      study emphasizes the importance of using more than one method for the correct
      identification of Aeromonas strains. The sequences of the rpoD gene enabled the
      unambiguous identication of the 94 Aeromonas isolates in accordance with results
      of other recent studies. Aeromonas aquariorum showed to be the most prevalent
      species (50%) containing an important subset of virulence genes
      lip/alt/ser/fla/aer. Different combinations of the virulence genes present in the
      isolates indicate their probable role in the pathogenesis of Aeromonas
      infections.

PMID- 22383959
TI  - A high variability of mixed infections and recent recombinations of hepatitis B
      virus in Laos.
AB  - In Lao PDR, where more than 8% of the population are chronic carriers of HBsAg,
      multiple genotypes and subgenotypes co-circulate and are prone to generate
      recombinant viruses. Phylogenetic analyses of multiple clones per donor revealed
      mixed infections of subgenotypes B1, B2, B4, C1, C5, I1 and I2 in almost 6% of
      HBsAg positive rejected blood donors. Recombination analyses and distance
      calculations furthermore showed that about 65% (17/26) of the mixed infected
      donors showed recombinations in the S-gene alone, involving the predominant
      genotypes B and C. These results suggest that, at least in Laos, hepatitis B
      virus (HBV) mixed infections lead to frequent recombinations. In many donors with
      recombinant strains, the recombinant fragment and a non-recombinant strain of the
      same genotype co-existed (127/185 analysed recombinant fragments). For a large
      proportion of these (60/127), the most closely related known virus was found,
      although not always exclusively, in the same donor. Recombinant virus strains are
      largely distinct. This is reflected in an unexpected diversity in recombination
      breakpoints and the relatively rare recombinations with identical recombination
      patterns of the same genotypes in different donors. Recent recombination events
      would explain the limited spread of each of the recombinants. Using a published
      mutation rate of 4.2 * 10(-5) mutations per site and year, the observed minimum
      genetic distances of 0-0.60% between parent strain and recombinant fragment would
      correspond to 0-71 years of evolution from a most recent common ancestor (MRCA).
      Thus several lines of evidence are suggestive of recent independent recombination
      events, a proportion of these even occurring within the same donors. In
      conclusion, our analyses revealed a high variability of mixed infections as a
      very probable breeding ground of multiple variable recombination events in Laos
      that so far have not led to new dominant strains.

PMID- 22383960
TI  - Inherent plasticity of brown adipogenesis in white fat of mice allows for
      recovery from effects of post-natal malnutrition.
AB  - Interscapular brown adipose tissue (iBAT) is formed during fetal development and
      stable for the life span of the mouse. In addition, brown adipocytes also appear
      in white fat depots (wBAT) between 10 and 21 days of age in mice maintained at a
      room temperature of 23  degrees C. However, this expression is transient. By 60
      days of age the brown adipocytes have disappeared, but they can re-emerge if the
      adult mouse is exposed to the cold (5  degrees C) or treated with beta3
      adrenergic agonists. Since the number of brown adipocytes that can be induced in
      white fat influences the capacity of the mouse to resist the obese state, we
      determined the effects of the nutritional conditions on post-natal development
      (birth to 21 days) of wBAT and its long-term effects on diet-induced obesity
      (DIO). Under-nutrition caused essentially complete suppression of wBAT in
      inguinal fat at 21 days of age, as indicated by expression of Ucp1 and genes of
      mitochondrial structure and function based upon microarray and qRT-PCR analysis,
      whereas over-nutrition had no discernible effects on wBAT induction.
      Surprisingly, the suppression of wBAT at 21 days of age did not affect DIO in
      adult mice maintained at 23  degrees C, nor did it affect the reduction in
      obesity or cold tolerance when DIO mice were exposed to the cold at 5  degrees C
      for one week. Gene expression analysis indicated that mice raised under
      conditions that suppressed wBAT at 21 days of age were able to normally induce
      wBAT as adults. Therefore, neither severe hypoleptinemia nor hypoinsulinemia
      during suckling permanently impaired brown adipogenesis in white fat. In
      addition, energy balance studies of DIO mice exposed to cold indicates that mice
      with reduced adipose stores preferentially increased food intake, whereas those
      with larger adipose tissue depots preferred to utilize energy from their adipose
      stores.

PMID- 22383961
TI  - Mosaic origins of a complex chimeric mitochondrial gene in Silene vulgaris.
AB  - Chimeric genes are significant sources of evolutionary innovation that are
      normally created when portions of two or more protein coding regions fuse to form
      a new open reading frame. In plant mitochondria astonishingly high numbers of
      different novel chimeric genes have been reported, where they are generated
      through processes of rearrangement and recombination. Nonetheless, because most
      studies do not find or report nucleotide variation within the same chimeric gene,
      evolution after the origination of these chimeric genes remains unstudied. Here
      we identify two alleles of a complex chimera in Silene vulgaris that are
      divergent in nucleotide sequence, genomic position relative to other
      mitochondrial genes, and expression patterns. Structural patterns suggest a
      history partially influenced by gene conversion between the chimeric gene and
      functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1). We
      identified small repeat structures within the chimeras that are likely
      recombination sites allowing generation of the chimera. These results establish
      the potential for chimeric gene divergence in different plant mitochondrial
      lineages within the same species. This result contrasts with the absence of
      diversity within mitochondrial chimeras found in crop species.

PMID- 22383962
TI  - HemaMaxTM, a recombinant human interleukin-12, is a potent mitigator of acute
      radiation injury in mice and non-human primates.
AB  - HemaMax, a recombinant human interleukin-12 (IL-12), is under development to
      address an unmet medical need for effective treatments against acute radiation
      syndrome due to radiological terrorism or accident when administered at least 24
      hours after radiation exposure. This study investigated pharmacokinetics,
      pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and
      HemaMax to increase survival after total body irradiation (TBI) in mice and
      rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an
      optimal 20 ng/mouse dose significantly increased percent survival and survival
      time when administered 24 hours after TBI between 8-9 Gy (p<0.05 Pearson's chi
      square test). This survival benefit was accompanied by increases in plasma
      interferon-gamma (IFN-gamma) and erythropoietin levels, recovery of femoral bone
      hematopoiesis characterized with the presence of IL-12 receptor beta2 subunit
      expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of
      jejunal radiation damage was also examined. At allometrically equivalent doses,
      HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax
      in mice, but more robustly increased plasma IFN-gamma levels. HemaMax also
      increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human
      primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg
      and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD(50/30))
      significantly increased percent survival of HemaMax groups compared to vehicle
      (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a
      significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and
      reticulocyte counts during nadir (days 12-14) and significantly less weight loss
      at day 12 compared to vehicle. These findings indicate successful interspecies
      dose conversion and provide proof of concept that HemaMax increases survival in
      irradiated rhesus monkeys by promoting hematopoiesis and recovery of immune
      functions and possibly gastrointestinal functions, likely through a network of
      interactions involving dendritic cells, osteoblasts, and soluble factors such as
      IL-12, IFN-gamma, and cytoprotectant erythropoietin.

PMID- 22383963
TI  - Motor agency: a new and highly sensitive measure to reveal agency disturbances in
      early psychosis.
AB  - BACKGROUND: Early diagnosis of young adults at risk of schizophrenia is essential
      for preventive approaches of the illness. Nevertheless, classic screening
      instruments are difficult to use because of the non-specific nature of the signs
      at this pre-onset phase of illness. The objective of the present contribution was
      to propose an innovating test that can probe the more specific symptom of
      psychosis, i.e., the sense of agency, which is defined as being the immediate
      experience of oneself as the cause of an action. More specifically, we tested
      whether motor agency is abnormal in early psychosis. METHODS: Thirty-two young
      symptomatic patients and their age-matched controls participated in the study. 15
      of these patients were at ultra high-risk for developing psychosis (UHR), and 17
      patients were suffering from first-episode psychosis (FEP). Patients'
      neurocognitive capacities were assessed through the use of seven
      neuropsychological tests. A motor agency task was also introduced to obtain an
      objective indicator of the degree of sense of agency, by contrasting force levels
      applied during other and self-produced collisions between a hand-held objet and a
      pendulum. RESULTS: As reported in the literature for adult controls, healthy
      adolescents used more efficient force levels in self than in other-imposed
      collisions. For both UHR and FEP patients, abnormally high levels of grip force
      were used for self-produced collisions, leading to an absence of difference
      between self and other. The normalized results revealed that motor agency
      differentiated patients from controls with a higher level of sensitivity than the
      more classic neuropsychological test battery. CONCLUSIONS: This study is in
      favour of the existence of an abnormal sense of agency early in the psychotic
      illness. Because it is quick and none verbal, motor agency may be a valuable tool
      to use in complement to classic interviews, especially when investigating complex
      ineffable experiences that are difficult to explicitly describe.

PMID- 22383965
TI  - Remote high-definition rotating video enables fast spatial survey of marine
      underwater macrofauna and habitats.
AB  - Observing spatial and temporal variations of marine biodiversity from non
      destructive techniques is central for understanding ecosystem resilience, and for
      monitoring and assessing conservation strategies, e.g. Marine Protected Areas.
      Observations are generally obtained through Underwater Visual Censuses (UVC)
      conducted by divers. The problems inherent to the presence of divers have been
      discussed in several papers. Video techniques are increasingly used for observing
      underwater macrofauna and habitat. Most video techniques that do not need the
      presence of a diver use baited remote systems. In this paper, we present an
      original video technique which relies on a remote unbaited rotating remote system
      including a high definition camera. The system is set on the sea floor to record
      images. These are then analysed at the office to quantify biotic and abiotic sea
      bottom cover, and to identify and count fish species and other species like
      marine turtles. The technique was extensively tested in a highly diversified
      coral reef ecosystem in the South Lagoon of New Caledonia, based on a protocol
      covering both protected and unprotected areas in major lagoon habitats. The
      technique enabled to detect and identify a large number of species, and in
      particular fished species, which were not disturbed by the system. Habitat could
      easily be investigated through the images. A large number of observations could
      be carried out per day at sea. This study showed the strong potential of this non
      obtrusive technique for observing both macrofauna and habitat. It offers a unique
      spatial coverage and can be implemented at sea at a reasonable cost by non-expert
      staff. As such, this technique is particularly interesting for investigating and
      monitoring coastal biodiversity in the light of current conservation challenges
      and increasing monitoring needs.

PMID- 22383964
TI  - TEPITOPEpan: extending TEPITOPE for peptide binding prediction covering over 700
      HLA-DR molecules.
AB  - MOTIVATION: Accurate identification of peptides binding to specific Major
      Histocompatibility Complex Class II (MHC-II) molecules is of great importance for
      elucidating the underlying mechanism of immune recognition, as well as for
      developing effective epitope-based vaccines and promising immunotherapies for
      many severe diseases. Due to extreme polymorphism of MHC-II alleles and the high
      cost of biochemical experiments, the development of computational methods for
      accurate prediction of binding peptides of MHC-II molecules, particularly for the
      ones with few or no experimental data, has become a topic of increasing interest.
      TEPITOPE is a well-used computational approach because of its good
      interpretability and relatively high performance. However, TEPITOPE can be
      applied to only 51 out of over 700 known HLA DR molecules. METHOD: We have
      developed a new method, called TEPITOPEpan, by extrapolating from the binding
      specificities of HLA DR molecules characterized by TEPITOPE to those
      uncharacterized. First, each HLA-DR binding pocket is represented by amino acid
      residues that have close contact with the corresponding peptide binding core
      residues. Then the pocket similarity between two HLA-DR molecules is calculated
      as the sequence similarity of the residues. Finally, for an uncharacterized HLA
      DR molecule, the binding specificity of each pocket is computed as a weighted
      average in pocket binding specificities over HLA-DR molecules characterized by
      TEPITOPE. RESULT: The performance of TEPITOPEpan has been extensively evaluated
      using various data sets from different viewpoints: predicting MHC binding
      peptides, identifying HLA ligands and T-cell epitopes and recognizing binding
      cores. Among the four state-of-the-art competing pan-specific methods, for
      predicting binding specificities of unknown HLA-DR molecules, TEPITOPEpan was
      roughly the second best method next to NETMHCIIpan-2.0. Additionally, TEPITOPEpan
      achieved the best performance in recognizing binding cores. We further analyzed
      the motifs detected by TEPITOPEpan, examining the corresponding literature of
      immunology. Its online server and PSSMs therein are available at
      http://www.biokdd.fudan.edu.cn/Service/TEPITOPEpan/.

PMID- 22383966
TI  - Contingent kernel density estimation.
AB  - Kernel density estimation is a widely used method for estimating a distribution
      based on a sample of points drawn from that distribution. Generally, in practice
      some form of error contaminates the sample of observed points. Such error can be
      the result of imprecise measurements or observation bias. Often this error is
      negligible and may be disregarded in analysis. In cases where the error is non
      negligible, estimation methods should be adjusted to reduce resulting bias.
      Several modifications of kernel density estimation have been developed to address
      specific forms of errors. One form of error that has not yet been addressed is
      the case where observations are nominally placed at the centers of areas from
      which the points are assumed to have been drawn, where these areas are of varying
      sizes. In this scenario, the bias arises because the size of the error can vary
      among points and some subset of points can be known to have smaller error than
      another subset or the form of the error may change among points. This paper
      proposes a "contingent kernel density estimation" technique to address this form
      of error. This new technique adjusts the standard kernel on a point-by-point
      basis in an adaptive response to changing structure and magnitude of error. In
      this paper, equations for our contingent kernel technique are derived, the
      technique is validated using numerical simulations, and an example using the
      geographic locations of social networking users is worked to demonstrate the
      utility of the method.

PMID- 22383967
TI  - Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue
      inflammation, steatohepatitis and insulin resistance.
AB  - The progression of obesity is accompanied by a chronic inflammatory process that
      involves both innate and acquired immunity. Natural killer T (NKT) cells
      recognize lipid antigens and are also distributed in adipose tissue. To examine
      the involvement of NKT cells in the development of obesity, C57BL/6 mice (wild
      type; WT), and two NKT-cell-deficient strains, Jalpha18(-/-) mice that lack the
      type I subset and CD1d(-/-) mice that lack both the type I and II subsets, were
      fed a high fat diet (HFD). CD1d(-/-) mice gained the least body weight with the
      least weight in perigonadal and brown adipose tissue as well as in the liver,
      compared to WT or Jalpha18(-/-) mice fed an HFD. Histologically, CD1d(-/-) mice
      had significantly smaller adipocytes and developed significantly milder
      hepatosteatosis than WT or Jalpha18(-/-) mice. The number of NK1.1(+)TCRbeta(+)
      cells in adipose tissue increased when WT mice were fed an HFD and were mostly
      invariant Valpha14Jalpha18-negative. CD11b(+) macrophages (Mphi) were another
      major subset of cells in adipose tissue infiltrates, and they were divided into
      F4/80(high) and F4/80(low) cells. The F4/80(low)-Mphi subset in adipose tissue
      was increased in CD1d(-/-) mice, and this population likely played an anti
      inflammatory role. Glucose intolerance and insulin resistance in CD1d(-/-) mice
      were not aggravated as in WT or Jalpha18(-/-) mice fed an HFD, likely due to a
      lower grade of inflammation and adiposity. Collectively, our findings provide
      evidence that type II NKT cells initiate inflammation in the liver and adipose
      tissue and exacerbate the course of obesity that leads to insulin resistance.

PMID- 22383968
TI  - Subliminally perceived odours modulate female intrasexual competition: an eye
      movement study.
AB  - BACKGROUND: Evidence suggests that subliminal odorants influence human perception
      and behavior. It has been hypothesized that the human sex-steroid derived
      compound 4,16-androstadien-3-one (androstadienone) functions as a human
      chemosignal. The most intensively studied steroid compound, androstadienone is
      known to be biologically relevant since it seems to convey information about male
      mate quality to women. It is unclear if the effects of androstadienone are
      menstrual cycle related. METHODOLOGY/PRINCIPAL FINDINGS: In the first experiment,
      heterosexual women were exposed to androstadienone or a control compound and
      asked to view stimuli such as female faces, male faces and familiar objects while
      their eye movements were recorded. In the second experiment the same women were
      asked to rate the level of stimuli attractiveness following exposure to the study
      or control compound. The results indicated that women at high conception risk
      spent more time viewing the female than the male faces regardless of the compound
      administered. Women at a low conception risk exhibited a preference for female
      faces only following exposure to androstadienone. CONCLUSIONS/SIGNIFICANCE: We
      contend that a woman's level of fertility influences her evaluation of potential
      competitors (e.g., faces of other women) during times critical for reproduction.
      Subliminally perceived odorants, such as androstadienone, might similarly enhance
      intrasexual competition strategies in women during fertility phases not critical
      for conception. These findings offer a substantial contribution to the current
      debate about the effects that subliminally perceived body odors might have on
      behavior.

PMID- 22383969
TI  - Maternal protein malnutrition does not impair insulin secretion from pancreatic
      islets of offspring after transplantation into diabetic rats.
AB  - Pancreatic islets from adult rats whose mothers were protein restricted during
      lactation undersecrete insulin. The current work analyzes whether this secretory
      dysfunction can be improved when the pancreatic islets are grafted into
      hyperglycemic diabetic rats. Two groups of rats were used: the adult offspring
      from dams that received a low protein diet (4%) during the initial 2/3 of
      lactation (LP) and, as a control, the adult offspring from dams that consumed a
      normal protein diet (23%) during the entire period of lactation (NP). Islets from
      NP- and LP-rats were transplanted into diabetic recipient rats, which were
      generated by streptozotocin treatment. The islets were transplanted via the
      portal vein under anesthesia. The fed blood glucose levels were monitored during
      the 4 days post-transplantation. Transplanted islets from LP-rats (T LP)
      decreased the fed glucose levels of diabetic rats 34% (21.37 +/- 0.24 mM,
      p<0.05); however, the levels still remained 2-fold higher than those of the sham
      operated controls (6.88 +/- 0.39 mM, p<0.05). Grafts with NP-islets (T NP)
      produced the same effect as the LP-islets in diabetic rats. The high fasting
      blood glucose levels of diabetic rats were improved by the transplantations.
      Islet grafts from both rat groups recovered 50% of the retroperitoneal fat mass
      of the diabetic rats (0.55 +/- 0.08 g/100 g of body weight for T NP and 0.56 +/-
      0.07 g/100 g of body weight for T LP, p<0.05). Because pancreatic islets from
      both the NP- and LP-rats were able to regulate fasting blood glucose
      concentrations in hyperglycemic rats, we propose that the altered function of
      pancreatic islets from LP-rats is not permanent.

PMID- 22383970
TI  - Gene profile of myeloid-derived suppressive cells from the bone marrow of
      lysosomal acid lipase knock-out mice.
AB  - BACKGROUND: Lysosomal acid lipase (LAL) controls development and homeostasis of
      myeloid lineage cells. Loss of the lysosomal acid lipase (LAL) function leads to
      expansion of myeloid-derived suppressive cells (MDSCs) that cause
      myeloproliferative neoplasm. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix GeneChip
      microarray analysis identified detailed intrinsic defects in Ly6G(+) myeloid
      lineage cells of LAL knock-out (lal-/-) mice. Ingenuity Pathway Analysis revealed
      activation of the mammalian target of rapamycin (mTOR) signaling, which functions
      as a nutrient/energy/redox sensor, and controls cell growth, cell cycle entry,
      cell survival, and cell motility. Loss of the LAL function led to major
      alteration of large GTPase and small GTPase signal transduction pathways. lal-/-
      Ly6G(+) myeloid cells in the bone marrow showed substantial increase of cell
      proliferation in association with up-regulation of cyclin and cyclin-dependent
      kinase (cdk) genes. The epigenetic microenvironment was significantly changed due
      to the increased expression of multiple histone cluster genes, centromere protein
      genes and chromosome modification genes. Gene expression of bioenergetic
      pathways, including glycolysis, aerobic glycolysis, mitochondrial oxidative
      phosphorylation, and respiratory chain proteins, was also increased, while the
      mitochondrial function was impaired in lal-/- Ly6G(+) myeloid cells. The
      concentration of reactive oxygen species (ROS) was significantly increased
      accompanied by up-regulation of nitric oxide/ROS production genes in these cells.
      CONCLUSIONS/SIGNIFICANCE: This comprehensive gene profile study for the first
      time identifies and defines important gene pathways involved in the myeloid
      lineage cells towards MDSCs using lal-/- mouse model.

PMID- 22383971
TI  - Analyzing thioflavin T binding to amyloid fibrils by an equilibrium microdialysis
      based technique.
AB  - A new approach for the determination of the amyloid fibril - thioflavin T (ThT)
      binding parameters (the number of binding modes, stoichiometry, and binding
      constants of each mode) is proposed. This approach is based on the absorption
      spectroscopy determination of the concentration of free and bound to fibril dye
      in solutions, which are prepared by equilibrium microdialysis. Furthermore, the
      proposed approach allowed us, for the first time, to determine the absorption
      spectrum, molar extinction coefficient, and fluorescence quantum yield of the ThT
      bound to fibril by each binding modes. This approach is universal and can be used
      for determining the binding parameters of any dye interaction with a receptor,
      such as ANS binding to proteins in the molten globule state or to protein
      amorphous aggregates.

PMID- 22383972
TI  - Factors affecting population dynamics of maternally transmitted endosymbionts in
      Bemisia tabaci.
AB  - While every individual of Bemisia tabaci (Hemiptera: Aleyrodidae) harbors the
      primary symbiont (P-symbiont) Portiera, the infection frequencies of the six
      secondary symbionts (S-symbionts) including Hamiltonella, Arsenophonus,
      Cardinium, Wolbachia, Rickettsia and Fritschea vary greatly among different
      populations. To characterize the factors influencing the infection dynamics of
      the six S-symbionts in B. tabaci, gene-specific PCR were conducted to screen for
      the presence of the P-symbiont Portiera and the six S-symbionts in 61 (17 B and
      44 Q biotypes) field populations collected from different plant species and
      locations in China. All individuals of the 61 populations hosted the P-symbiont
      Portiera, but none of them harbored Arsenophonus and Fritschea. The presence and
      infection rates of Hamiltonella, Cardinium, Rickettsia, Wolbachia and their co
      infections Rickettsia + Hamiltonella (RH), Rickettsia + Cardinium (RC),
      Hamiltonella + Cardinium (HC) and Rickettsia + Hamiltonella + Cardinium (RHC)
      varied significantly among the 61 field populations; and the observed variations
      can be explained by biotypes, sexes, host plants and geographical locations of
      these field populations. Taken together, at least three factors including
      biotype, host plant and geographical location affect the infection dynamics of S
      symbionts in B. tabaci.

PMID- 22383973
TI  - Mosquitoes LTR retrotransposons: a deeper view into the genomic sequence of Culex
      quinquefasciatus.
AB  - A set of 67 novel LTR-retrotransposon has been identified by in silico analyses
      of the Culex quinquefasciatus genome using the LTR_STRUC program. The
      phylogenetic analysis shows that 29 novel and putatively functional LTR
      retrotransposons detected belong to the Ty3/gypsy group. Our results demonstrate
      that, by considering only families containing potentially autonomous LTR
      retrotransposons, they account for about 1% of the genome of C. quinquefasciatus.
      In previous studies it has been estimated that 29% of the genome of C.
      quinquefasciatus is occupied by mobile genetic elements.The potential role of
      retrotransposon insertions strictly associated with host genes is described and
      discussed along with the possible origin of a retrotransposon with peculiar
      Primer Binding Site region. Finally, we report the presence of a group of 38
      retrotransposons, carrying tandem repeated sequences but lacking coding
      potential, and apparently lacking "master copy" elements from which they could
      have originated. The features of the repetitive sequences found in these non
      autonomous LTR retrotransposons are described, and their possible role
      discussed.These results integrate the existing data on the genomics of an
      important virus-borne disease vector.

PMID- 22383974
TI  - Circadian rhythms of fetal liver transcription persist in the absence of
      canonical circadian clock gene expression rhythms in vivo.
AB  - The cellular circadian clock and systemic cues drive rhythmicity in the
      transcriptome of adult peripheral tissues. However, the oscillating status of the
      circadian clocks in fetal tissues, and their response to maternal cues, are less
      clear. Most clock genes do not cycle in fetal livers from mice and rats, although
      tissue level rhythms rapidly emerge when fetal mouse liver explants are cultured
      in vitro. Thus, in the fetal mouse liver, the circadian clock does not oscillate
      at the cellular level (but is induced to oscillate in culture). To gain a
      comprehensive overview of the clock status in the fetal liver during late
      gestation, we performed microarray analyses on fetal liver tissues. In the fetal
      liver we did not observe circadian rhythms of clock gene expression or many other
      transcripts known to be rhythmically expressed in the adult liver. Nevertheless,
      JTK_CYCLE analysis identified some transcripts in the fetal liver that were
      rhythmically expressed, albeit at low amplitudes. Upon data filtering by
      coefficient of variation, the expression levels for transcripts related to
      pancreatic exocrine enzymes and zymogen secretion were found to undergo
      synchronized daily fluctuations at high amplitudes. These results suggest that
      maternal cues influence the fetal liver, despite the fact that we did not detect
      circadian rhythms of canonical clock gene expression in the fetal liver. These
      results raise important questions on the role of the circadian clock, or lack
      thereof, during ontogeny.

PMID- 22383975
TI  - FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with
      MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features.
AB  - Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have
      been identified in endometrial cancer. The aim of this study was to provide
      insight into the clinicopathological features associated with patterns of
      mutation in these genes, a necessary step in planning targeted therapies for
      endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations
      in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status,
      tumor microsatellite instability (MSI) and clinicopathological features including
      overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan
      Meier survival analysis and Cox proportional hazard models. Mutations were
      identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA
      (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1
      mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near
      mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and
      CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002).
      Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p
      = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with
      early stage disease (stage I and II), FGFR2 mutation was significantly associated
      with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008)
      and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with
      longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS
      and FGFR2 mutations share similar activation of the MAPK pathway, our data
      suggest very different roles in tumor biology. This has implications for the
      implementation of anti-FGFR or anti-MEK biologic therapies.

PMID- 22383976
TI  - Evaluation of multi-scale climate effects on annual recruitment levels of the
      Japanese eel, Anguilla japonica, to Taiwan.
AB  - Long-term (1967-2008) glass eel catches were used to investigate climatic effects
      on the annual recruitment of Japanese eel to Taiwan. Specifically, three
      prevailing hypotheses that potentially explain the annual recruitment were
      evaluated. Hypothesis 1: high precipitation shifts the salinity front northward,
      resulting in favorable spawning locations. Hypothesis 2: a southward shift of the
      position of the North Equatorial Current (NEC) bifurcation provides a favorable
      larval transport route. Hypothesis 3: ocean conditions (eddy activities and
      productivity) along the larval migration route influence larval survival. Results
      of time series regression and wavelet analyses suggest that Hypothesis 1 is not
      supported, as the glass eel catches exhibited a negative relationship with
      precipitation. Hypothesis 2 is plausible. However, the catches are correlated
      with the NEC bifurcation with a one-year lag. Considering the time needed for
      larval transport (only four to six months), the one-year lag correlation does not
      support the direct transport hypothesis. Hypothesis 3 is supported indirectly by
      the results. Significant correlations were found between catches and climate
      indices that affect ocean productivity and eddy activities, such as the Quasi
      Biennial Oscillation (QBO), North Pacific Gyre Oscillation (NPGO), Pacific
      Decadal Oscillation (PDO), and Western Pacific Oscillation (WPO). Wavelet
      analysis reveals three periodicities of eel catches: 2.7, 5.4, and 10.3 years.
      The interannual coherence with QBO and the Nino 3.4 region suggests that the
      shorter-term climate variability is modulated zonally by equatorial dynamics. The
      low-frequency coherence with WPO, PDO, and NPGO demonstrates the decadal
      modulation of meridional teleconnection via ocean-atmosphere interactions.
      Furthermore, WPO and QBO are linked to solar activities. These results imply that
      the Japanese eel recruitment may be influenced by multi-timescale climate
      variability. Our findings call for investigation of extra-tropical ocean dynamics
      that affect survival of eels during transport, in addition to the existing
      efforts to study the equatorial system.

PMID- 22383977
TI  - A mathematical model of mitotic exit in budding yeast: the role of Polo kinase.
AB  - Cell cycle progression in eukaryotes is regulated by periodic activation and
      inactivation of a family of cyclin-dependent kinases (Cdk's). Entry into mitosis
      requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from
      mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their
      targeted proteins. Mitotic exit in budding yeast is known to involve the
      interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A
      and Cdc14), as well as the action of the anaphase promoting complex (APC) in
      degrading specific proteins in anaphase and telophase. To understand the
      intricacies of this mechanism, we propose a mathematical model for the molecular
      events during mitotic exit in budding yeast. The model captures the dynamics of
      this network in wild-type yeast cells and 110 mutant strains. The model clarifies
      the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway
      and in the G-protein regulated mitotic exit network.

PMID- 22383978
TI  - Clinical presentation of acute pulmonary embolism: survey of 800 cases.
AB  - BACKGROUND: Pulmonary embolism (PE) is a common and potentially fatal disease
      that is still underdiagnosed. The objective of our study was to reappraise the
      clinical presentation of PE with emphasis on the identification of the symptoms
      and signs that prompt the patients to seek medical attention.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied 800 patients with PE from two
      different clinical settings: 440 were recruited in Pisa (Italy) as part of the
      Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISAPED);
      360 were diagnosed with and treated for PE in seven hospitals of central Tuscany,
      and evaluated at the Atherothrombotic Disorders Unit, Firenze (Italy), shortly
      after hospital discharge. We interviewed the patients directly using a
      standardized, self-administered questionnaire originally utilized in the PISAPED.
      The two samples differed significantly as regards age, proportion of outpatients,
      prevalence of unprovoked PE, and of active cancer. Sudden onset dyspnea was the
      most frequent symptom in both samples (81 and 78%), followed by chest pain (56
      and 39%), fainting or syncope (26 and 22%), and hemoptysis (7 and 5%). At least
      one of the above symptoms was reported by 756 (94%) of 800 patients. Isolated
      symptoms and signs of deep vein thrombosis occurred in 3% of the cases. Only 7
      (1%) of 800 patients had no symptoms before PE was diagnosed.
      CONCLUSIONS/SIGNIFICANCE: Most patients with PE feature at least one of four
      symptoms which, in decreasing order of frequency, are sudden onset dyspnea, chest
      pain, fainting (or syncope), and hemoptysis. The occurrence of such symptoms, if
      not explained otherwise, should alert the clinicians to consider PE in
      differential diagnosis, and order the appropriate objective test.

PMID- 22383979
TI  - Development of genomic resources for Pacific Herring through targeted
      transcriptome pyrosequencing.
AB  - Pacific herring (Clupea pallasii) support commercially and culturally important
      fisheries but have experienced significant additional pressure from a variety of
      anthropogenic and environmental sources. In order to provide genomic resources to
      facilitate organismal and population level research, high-throughput
      pyrosequencing (Roche 454) was carried out on transcriptome libraries from liver
      and testes samples taken in Prince William Sound, the Bering Sea, and the Gulf of
      Alaska. Over 40,000 contigs were identified with an average length of 728 bp. We
      describe an annotated transcriptome as well as a workflow for single nucleotide
      polymorphism (SNP) discovery and validation. A subset of 96 candidate SNPs chosen
      from 10,933 potential SNPs, were tested using a combination of Sanger sequencing
      and high-resolution melt-curve analysis. Five SNPs supported between-ocean-basin
      differentiation, while one SNP associated with immune function provided high
      differentiation between Prince William Sound and Kodiak Island within the Gulf of
      Alaska. These genomic resources provide a basis for environmental physiology
      studies and opportunities for marker development and subsequent population
      structure analysis.

PMID- 22383980
TI  - Dilated thin-walled blood and lymphatic vessels in human endometrium: a potential
      role for VEGF-D in progestin-induced break-through bleeding.
AB  - Progestins provide safe, effective and cheap options for contraception as well as
      the treatment of a variety of gynaecological disorders. Episodes of irregular
      endometrial bleeding or breakthrough bleeding (BTB) are a major unwanted side
      effect of progestin treatment, such that BTB is the leading cause for
      discontinued use of an otherwise effective and popular medication. The cellular
      mechanisms leading to BTB are poorly understood. In this study, we make the novel
      finding that the large, dilated, thin walled vessels characteristic of human
      progestin-treated endometrium include both blood and lymphatic vessels. Increased
      blood and lymphatic vessel diameter are features of VEGF-D action in other
      tissues and we show by immunolocalisation and Western blotting that stromal cell
      decidualisation results in a significant increase in VEGF-D protein production,
      particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse
      model with xenografted human endometrium we were able to show that progestin
      treatment causes decidualisation, VEGF-D production and endometrial vessel
      dilation. Our results lead to a novel hypothesis to explain BTB, with stromal
      cell decidualisation rather than progestin treatment per se being the proposed
      causative event, and VEGF-D being the proposed effector agent.

PMID- 22383981
TI  - Ex vivo and in vivo neuroprotection induced by argon when given after an
      excitotoxic or ischemic insult.
AB  - In vitro studies have well established the neuroprotective action of the noble
      gas argon. However, only limited data from in vivo models are available, and
      particularly whether postexcitotoxic or postischemic argon can provide
      neuroprotection in vivo still remains to be demonstrated. Here, we investigated
      the possible neuroprotective effect of postexcitotoxic-postischemic argon both ex
      vivo in acute brain slices subjected to ischemia in the form of oxygen and
      glucose deprivation (OGD), and in vivo in rats subjected to an intrastriatal
      injection of N-methyl-D-aspartate (NMDA) or to the occlusion of middle-cerebral
      artery (MCAO). We show that postexcitotoxic-postischemic argon reduces OGD
      induced cell injury in brain slices, and further reduces NMDA-induced brain
      damage and MCAO-induced cortical brain damage in rats. Contrasting with its
      beneficial effect at the cortical level, we show that postischemic argon
      increases MCAO-induced subcortical brain damage and provides no improvement of
      neurologic outcome as compared to control animals. These results extend previous
      data on the neuroprotective action of argon. Particularly, taken together with
      previous in vivo data that have shown that intraischemic argon has
      neuroprotective action at both the cortical and subcortical level, our findings
      on postischemic argon suggest that this noble gas could be administered during
      but not after ischemia, i.e. before but not after reperfusion has occurred, in
      order to provide cortical neuroprotection and to avoid increasing subcortical
      brain damage. Also, the effects of argon are discussed as regards to the oxygen
      like chemical, pharmacological, and physical properties of argon.

PMID- 22383982
TI  - Testing the emergence of New Caledonia: fig wasp mutualism as a case study and a
      review of evidence.
AB  - While geologists suggest that New Caledonian main island (Grande Terre) was
      submerged until ca 37 Ma, biologists are struck by the presence of supposedly
      Gondwanan groups on the island. Among these groups are the Oreosycea fig trees
      (Ficus, Moraceae) and their Dolichoris pollinators (Hymenoptera, Agaonidae).
      These partners are distributed in the Paleotropics and Australasia, suggesting
      that their presence on New Caledonia could result from Gondwanan vicariance. To
      test this hypothesis, we obtained mitochondrial and nuclear markers (5.3 kb) from
      28 species of Dolichoris, used all available sequences for Oreosycea, and
      conducted phylogenetic and dating analyses with several calibration strategies.
      All our analyses ruled out a vicariance scenario suggesting instead that New
      Caledonian colonization by Dolichoris and Oreosycea involved dispersal across
      islands from Sundaland ca 45.9-32.0 Ma. Our results show that successful long
      distance dispersal of obligate mutualists may happen further suggesting that
      presence of intimate mutualisms on isolated islands should not be used as a
      priori evidence for vicariance. Comparing our results to a review of all the
      published age estimates for New Caledonian plant and animal taxa, we showed that
      support for a vicariant origin of the island biota is still lacking. Finally, as
      demonstrating a causal relationship between geology and biology requires
      independent evidence, we argue that a priori assumptions about vicariance or
      dispersal should not be used to constrain chronograms. This circular reasoning
      could lead to under or overestimation of age estimates.

PMID- 22383983
TI  - P. falciparum in vitro killing rates allow to discriminate between different
      antimalarial mode-of-action.
AB  - Chemotherapy is still the cornerstone for malaria control. Developing drugs
      against Plasmodium parasites and monitoring their efficacy requires methods to
      accurately determine the parasite killing rate in response to treatment. Commonly
      used techniques essentially measure metabolic activity as a proxy for parasite
      viability. However, these approaches are susceptible to artefacts, as viability
      and metabolism are two parameters that are coupled during the parasite life cycle
      but can be differentially affected in response to drug actions. Moreover,
      traditional techniques do not allow to measure the speed-of-action of compounds
      on parasite viability, which is an essential efficacy determinant. We present
      here a comprehensive methodology to measure in vitro the direct effect of
      antimalarial compounds over the parasite viability, which is based on limiting
      serial dilution of treated parasites and re-growth monitoring. This methodology
      allows to precisely determine the killing rate of antimalarial compounds, which
      can be quantified by the parasite reduction ratio and parasite clearance time,
      which are key mode-of-action parameters. Importantly, we demonstrate that this
      technique readily permits to determine compound killing activities that might be
      otherwise missed by traditional, metabolism-based techniques. The analysis of a
      large set of antimalarial drugs reveals that this viability-based assay allows to
      discriminate compounds based on their antimalarial mode-of-action. This approach
      has been adapted to perform medium throughput screening, facilitating the
      identification of fast-acting antimalarial compounds, which are crucially needed
      for the control and possibly the eradication of malaria.

PMID- 22383984
TI  - Identification of genome-wide variations among three elite restorer lines for
      hybrid-rice.
AB  - Rice restorer lines play an important role in three-line hybrid rice production.
      Previous research based on molecular tagging has suggested that the restorer
      lines used widely today have narrow genetic backgrounds. However, patterns of
      genetic variation at a genome-wide scale in these restorer lines remain largely
      unknown. The present study performed re-sequencing and genome-wide variation
      analysis of three important representative restorer lines, namely, IR24, MH63,
      and SH527, using the Solexa sequencing technology. With the genomic sequence of
      the Indica cultivar 9311 as the reference, the following genetic features were
      identified: 267,383 single-nucleotide polymorphisms (SNPs), 52,847
      insertion/deletion polymorphisms (InDels), and 3,286 structural variations (SVs)
      in the genome of IR24; 288,764 SNPs, 59,658 InDels, and 3,226 SVs in MH63; and
      259,862 SNPs, 55,500 InDels, and 3,127 SVs in SH527. Variations between samples
      were also determined by comparative analysis of authentic collections of SNPs,
      InDels, and SVs, and were functionally annotated. Furthermore, variations in
      several important genes were also surveyed by alignment analysis in these lines.
      Our results suggest that genetic variations among these lines, although far lower
      than those reported in the landrace population, are greater than expected,
      indicating a complicated genetic basis for the phenotypic diversity of the
      restorer lines. Identification of genome-wide variation and pattern analysis
      among the restorer lines will facilitate future genetic studies and the molecular
      improvement of hybrid rice.

PMID- 22383985
TI  - Hemodialysis removes uremic toxins that alter the biological actions of
      endothelial cells.
AB  - Chronic kidney disease is linked to systemic inflammation and to an increased
      risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction
      associates with hypertension and vascular disease in the presence of chronic
      kidney disease but the mechanisms that regulate the activation of the endothelium
      at the early stages of the disease, before systemic inflammation is established
      remain obscure. In the present study we investigated the effect of serum derived
      from patients with chronic kidney disease either before or after hemodialysis on
      the activation of human endothelial cells in vitro, as an attempt to define the
      overall effect of uremic toxins at the early stages of endothelial dysfunction.
      Our results argue that uremic toxins alter the biological actions of endothelial
      cells and the remodelling of the extracellular matrix before signs of systemic
      inflammatory responses are observed. This study further elucidates the early
      events of endothelial dysfunction during toxic uremia conditions allowing more
      complete understanding of the molecular events as well as their sequence during
      progressive renal failure.

PMID- 22383986
TI  - A bistable model of cell polarity.
AB  - Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for
      a long time as a way to realize bistable switches in biological systems. It is
      not as well recognized that when ultrasensitivity and reinforcing feedback loops
      are present in a spatially distributed system such as the cell plasmamembrane,
      they may induce bistability and spatial separation of the system into distinct
      signaling phases. Here we suggest that bistability of ultrasensitive signaling
      pathways in a diffusive environment provides a basic mechanism to realize cell
      membrane polarity. Cell membrane polarization is a fundamental process implicated
      in several basic biological phenomena, such as differentiation, proliferation,
      migration and morphogenesis of unicellular and multicellular organisms. We
      describe a simple, solvable model of cell membrane polarization based on the
      coupling of membrane diffusion with bistable enzymatic dynamics. The model can
      reproduce a broad range of symmetry-breaking events, such as those observed in
      eukaryotic directional sensing, the apico-basal polarization of epithelium cells,
      the polarization of budding and mating yeast, and the formation of Ras
      nanoclusters in several cell types.

PMID- 22383988
TI  - A format for phylogenetic placements.
AB  - We have developed a unified format for phylogenetic placements, that is, mappings
      of environmental sequence data (e.g., short reads) into a phylogenetic tree. We
      are motivated to do so by the growing number of tools for computing and post
      processing phylogenetic placements, and the lack of an established standard for
      storing them. The format is lightweight, versatile, extensible, and is based on
      the JSON format, which can be parsed by most modern programming languages. Our
      format is already implemented in several tools for computing and post-processing
      parsimony- and likelihood-based phylogenetic placements and has worked well in
      practice. We believe that establishing a standard format for analyzing read
      placements at this early stage will lead to a more efficient development of
      powerful and portable post-analysis tools for the growing applications of
      phylogenetic placement.

PMID- 22383987
TI  - Emotional cues during simultaneous face and voice processing:
      electrophysiological insights.
AB  - Both facial expression and tone of voice represent key signals of emotional
      communication but their brain processing correlates remain unclear. Accordingly,
      we constructed a novel implicit emotion recognition task consisting of
      simultaneously presented human faces and voices with neutral, happy, and angry
      valence, within the context of recognizing monkey faces and voices task. To
      investigate the temporal unfolding of the processing of affective information
      from human face-voice pairings, we recorded event-related potentials (ERPs) to
      these audiovisual test stimuli in 18 normal healthy subjects; N100, P200, N250,
      P300 components were observed at electrodes in the frontal-central region, while
      P100, N170, P270 were observed at electrodes in the parietal-occipital region.
      Results indicated a significant audiovisual stimulus effect on the amplitudes and
      latencies of components in frontal-central (P200, P300, and N250) but not the
      parietal occipital region (P100, N170 and P270). Specifically, P200 and P300
      amplitudes were more positive for emotional relative to neutral audiovisual
      stimuli, irrespective of valence, whereas N250 amplitude was more negative for
      neutral relative to emotional stimuli. No differentiation was observed between
      angry and happy conditions. The results suggest that the general effect of
      emotion on audiovisual processing can emerge as early as 200 msec (P200 peak
      latency) post stimulus onset, in spite of implicit affective processing task
      demands, and that such effect is mainly distributed in the frontal-central
      region.

PMID- 22383989
TI  - Genetic susceptibility on CagA-interacting molecules and gene-environment
      interaction with phytoestrogens: a putative risk factor for gastric cancer.
AB  - OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules
      (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer
      risk and whether an interaction between these genes and phytoestrogens modify
      gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven
      genes were analyzed in 76 incident gastric cancer cases and 322 matched controls
      from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes
      (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the
      extension phase. Odds ratios (ORs) for gastric cancer risk were estimated
      adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity.
      Summarized ORs in the total study population (462 cases and 670 controls) were
      presented using pooled- and meta-analysis. Plasma concentrations of
      phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using
      the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET
      rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer
      in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95%
      CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37
      [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95%
      CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57],
      respectively). Risk allele of CRK rs7208768 had a significantly increased risk
      for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS:
      Our findings suggest that SRC, c-MET and CRK play a key role in gastric
      carcinogenesis by modulating CagA signal transductions and interaction between
      CRK gene and phytoestrogens modify gastric cancer risk.

PMID- 22383990
TI  - The abundance of pink-pigmented facultative methylotrophs in the root zone of
      plant species in invaded coastal sage scrub habitat.
AB  - Pink-pigmented facultative methylotrophic bacteria (PPFMs) are associated with
      the roots, leaves and seeds of most terrestrial plants and utilize volatile C(1)
      compounds such as methanol generated by growing plants during cell division.
      PPFMs have been well studied in agricultural systems due to their importance in
      crop seed germination, yield, pathogen resistance and drought stress tolerance.
      In contrast, little is known about the PPFM abundance and diversity in natural
      ecosystems, let alone their interactions with non-crop species. Here we surveyed
      PPFM abundance in the root zone soil of 5 native and 5 invasive plant species
      along ten invasion gradients in Southern California coastal sage scrub habitat.
      PPFMs were present in every soil sample and ranged in abundance from 10(2) to
      10(5) CFU/g dry soil. This abundance varied significantly among plant species.
      PPFM abundance was 50% higher in the root zones of annual or biennial species
      (many invasives) than perennial species (all natives). Further, PPFM abundance
      appears to be influenced by the plant community beyond the root zone; pure stands
      of either native or invasive species had 50% more PPFMs than mixed species
      stands. In sum, PPFM abundance in the root zone of coastal sage scrub plants is
      influenced by both the immediate and surrounding plant communities. The results
      also suggest that PPFMs are a good target for future work on plant-microorganism
      feedbacks in natural ecosystems.

PMID- 22383991
TI  - Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases.
AB  - Breast cancer can be caused by germline mutations in several genes that are
      responsible for different hereditary cancer syndromes. Some of the genes causing
      the Fanconi anemia (FA) syndrome, such as BRCA2, BRIP1, PALB2, and RAD51C, are
      associated with high or moderate risk of developing breast cancer. Very recently,
      SLX4 has been established as a new FA gene raising the question of its
      implication in breast cancer risk. This study aimed at answering this question
      sequencing the entire coding region of SLX4 in 526 familial breast cancer cases
      from Italy. We found 81 different germline variants and none of these were
      clearly pathogenic. The statistical power of our sample size allows concluding
      that in Italy the frequency of carriers of truncating mutations of SLX4 may not
      exceed 0.6%. Our results indicate that testing for SLX4 germline mutations is
      unlikely to be relevant for the identification of individuals at risk of breast
      cancer, at least in the Italian population.

PMID- 22383992
TI  - Molecular characterization, tissue distribution, subcellular localization and
      actin-sequestering function of a thymosin protein from silkworm.
AB  - We identified a novel gene encoding a Bombyx mori thymosin (BmTHY) protein from a
      cDNA library of silkworm pupae, which has an open reading frame (ORF) of 399 bp
      encoding 132 amino acids. It was found by bioinformatics that BmTHY gene
      consisted of three exons and two introns and BmTHY was highly homologous to
      thymosin betas (Tbeta). BmTHY has a conserved motif LKHTET with only one amino
      acid difference from LKKTET, which is involved in Tbeta binding to actin. A His
      tagged BmTHY fusion protein (rBmTHY) with a molecular weight of approximately
      18.4 kDa was expressed and purified to homogeneity. The purified fusion protein
      was used to produce anti-rBmTHY polyclonal antibodies in a New Zealand rabbit.
      Subcellular localization revealed that BmTHY can be found in both Bm5 cell (a
      silkworm ovary cell line) nucleus and cytoplasm but is primarily located in the
      nucleus. Western blotting and real-time RT-PCR showed that during silkworm
      developmental stages, BmTHY expression levels are highest in moth, followed by
      instar larvae, and are lowest in pupa and egg. BmTHY mRNA was universally
      distributed in most of fifth-instar larvae tissues (except testis). However,
      BmTHY was expressed in the head, ovary and epidermis during the larvae stage.
      BmTHY formed complexes with actin monomer, inhibited actin polymerization and
      cross-linked to actin. All the results indicated BmTHY might be an actin
      sequestering protein and participate in silkworm development.

PMID- 22383994
TI  - Rapid identification of bio-molecules applied for detection of biosecurity agents
      using rolling circle amplification.
AB  - Detection and identification of pathogens in environmental samples for
      biosecurity applications are challenging due to the strict requirements on
      specificity, sensitivity and time. We have developed a concept for quick,
      specific and sensitive pathogen identification in environmental samples. Target
      identification is realized by padlock- and proximity probing, and reacted probes
      are amplified by RCA (rolling-circle amplification). The individual RCA products
      are labeled by fluorescence and enumerated by an instrument, developed for
      sensitive and rapid digital analysis. The concept is demonstrated by
      identification of simili biowarfare agents for bacteria (Escherichia coli and
      Pantoea agglomerans) and spores (Bacillus atrophaeus) released in field.

PMID- 22383993
TI  - A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T
      cells and correlates with enhanced immunity in patients with glioblastoma.
AB  - BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic
      depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the
      high affinity interleukin-2 (IL-2) receptor (IL-2Ralpha/CD25) can enhance anti
      tumor immunotherapy. However, therapeutic approaches are complicated by the
      inadvertent inhibition of IL-2Ralpha expressing anti-tumor effector T-cells.
      OBJECTIVE: To determine if changes in the cytokine milieu during lymphopenia may
      engender differential signaling requirements that would enable unarmed anti-IL
      2Ralpha monoclonal antibody (MAbs) to selectively deplete T(Regs) while
      permitting vaccine-stimulated immune responses. METHODOLOGY: A randomized placebo
      controlled pilot study was undertaken to examine the ability of the anti-IL
      2Ralpha MAb daclizumab, given at the time of epidermal growth factor receptor
      variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively
      deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting
      temozolomide (TMZ). RESULTS AND CONCLUSIONS: Daclizumab treatment (n = 3) was
      well-tolerated with no symptoms of autoimmune toxicity and resulted in a
      significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in
      comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001)
      inverse correlation between the frequency of TRegs and the level of EGFRvIII
      specific humoral responses suggests the depletion of TRegs may be linked to
      increased vaccine-stimulated humoral immunity. These data suggest this approach
      deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00626015.

PMID- 22383995
TI  - Fetal myocardium in the kidney capsule: an in vivo model of repopulation of
      myocytes by bone marrow cells.
AB  - Debate surrounds the question of whether the heart is a post-mitotic organ in
      part due to the lack of an in vivo model in which myocytes are able to actively
      regenerate. The current study describes the first such mouse model--a fetal
      myocardial environment grafted into the adult kidney capsule. Here it is used to
      test whether cells descended from bone marrow can regenerate cardiac myocytes.
      One week after receiving the fetal heart grafts, recipients were lethally
      irradiated and transplanted with marrow from green fluorescent protein (GFP)
      expressing C57Bl/6J (B6) donors using normal B6 recipients and fetal donors.
      Levels of myocyte regeneration from GFP marrow within both fetal myocardium and
      adult hearts of recipients were evaluated histologically. Fetal myocardium
      transplants had rich neovascularization and beat regularly after 2 weeks,
      continuing at checkpoints of 1, 2, 4, 6, 8 and12 months after transplantation. At
      each time point, GFP-expressing rod-shaped myocytes were found in the fetal
      myocardium, but only a few were found in the adult hearts. The average count of
      repopulated myocardium with green rod-shaped myocytes was 996.8 cells per gram of
      fetal myocardial tissue, and 28.7 cells per adult heart tissue, representing a
      thirty-five fold increase in fetal myocardium compared to the adult heart at 12
      months (when numbers of green rod-shaped myocytes were normalized to per gram of
      myocardial tissue). Thus, bone marrow cells can differentiate to myocytes in the
      fetal myocardial environment. The novel in vivo model of fetal myocardium in the
      kidney capsule appears to be valuable for testing repopulating abilities of
      potential cardiac progenitors.

PMID- 22383996
TI  - Cocoa, hazelnuts, sterols and soluble fiber cream reduces lipids and inflammation
      biomarkers in hypertensive patients: a randomized controlled trial.
AB  - BACKGROUND: Cocoa, mixed with other food ingredients, intake can have beneficial
      effects on cardiovascular disease (CVD) biomarkers. We compared the effects of 4
      cocoa cream products on some of these biomarkers. METHODS AND FINDINGS: In this
      multi-centered, randomized, controlled, double-blind, parallel trial, volunteers
      (n = 113; age range: 43-65 years) who were pre-hypertensive, stage-1 hypertensive
      and hypercholesterolemic received one of 4 cocoa cream products (13 g/unit; 1 g
      cocoa/unit, 6 units/d; 465 Kcal/d) added to a low saturated fat diet for 4 weeks.
      The groups were: A) (n = 28), cocoa cream considered as control; B) (n = 28),
      cocoa+hazelnut cream (30 g/d hazelnuts); C) (n = 30),
      cocoa+hazelnuts+phytosterols (2 g/d); and D) (n = 27),
      cocoa+hazelnuts+phytosterols+soluble fiber (20 g/d) the patented "LMN product".
      Primary outcome measures were BP, LDL-c, apolipoprotein B-100 (Apo B), ApoB/ApoA
      ratio, oxidized LDL (oxLDL) and high-sensitive C-reactive protein (hsCRP)
      determined at baseline and post-cocoa cream product intake. Statistical analysis
      used was ANCOVA or mixed models (in case of repeated measurements), with baseline
      observation included as a covariate. After 4 weeks, compared to product A,
      product C reduced LDL-c by 11.2%, Apo B by 8.1% and ApoB/ApoA ratio by 7.8% (P =
      0.01). LMN decreased LDL-c by 9.2%, Apo B-100 by 8.5%, ApoB/ApoA ratio by 10.5%,
      hsCRP by 33.4% and oxLDL by 5.9% (P = 0.01). Surprisingly, even "control" product
      A reduced systolic BP (-7.89 mmHg; 95%CI: -11.45 to -4.3) and diastolic BP (-5.54
      mmHg; 95%CI: -7.79 to -3.29). The BP reductions were similar with the other 3
      products. Limitations of the study are that the trial period was relatively short
      and that a better "BP control" product would have been preferable. CONCLUSION:
      The creams (particularly the LMN) have anti-inflammatory and antioxidant effects
      in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble fiber
      effects amplified with sterols (as contained in the cocoa creams) provide new
      dietary therapeutic perspectives. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00511420.

PMID- 22383998
TI  - Mechanical work as an indirect measure of subjective costs influencing human
      movement.
AB  - To descend a flight of stairs, would you rather walk or fall? Falling seems to
      have some obvious disadvantages such as the risk of pain or injury. But the
      preferred strategy of walking also entails a cost for the use of active muscles
      to perform negative work. The amount and distribution of work a person chooses to
      perform may, therefore, reflect a subjective valuation of the trade-offs between
      active muscle effort and other costs, such as pain. Here we use a simple jump
      landing experiment to quantify the work humans prefer to perform to dissipate the
      energy of landing. We found that healthy normal subjects (N = 8) preferred a
      strategy that involved performing 37% more negative work than minimally necessary
      (P<0.001) across a range of landing heights. This then required additional
      positive work to return to standing rest posture, highlighting the cost of this
      preference. Subjects were also able to modulate the amount of landing work, and
      its distribution between active and passive tissues. When instructed to land
      softly, they performed 76% more work than necessary (P<0.001), with a higher
      proportion from active muscles (89% vs. 84%, P<0.001). Stiff-legged landings,
      performed by one subject for demonstration, exhibited close to the minimum of
      work, with more of it performed passively through soft tissue deformations (at
      least 30% in stiff landings vs. 16% preferred). During jump landings, humans
      appear not to minimize muscle work, but instead choose to perform a consistent
      amount of extra work, presumably to avoid other subjective costs. The degree to
      which work is not minimized may indirectly quantify the relative valuation of
      costs that are otherwise difficult to measure.

PMID- 22383997
TI  - Brain deletion of insulin receptor substrate 2 disrupts hippocampal synaptic
      plasticity and metaplasticity.
AB  - OBJECTIVE: Diabetes mellitus is associated with cognitive deficits and an
      increased risk of dementia, particularly in the elderly. These deficits and the
      corresponding neurophysiological structural and functional alterations are linked
      to both metabolic and vascular changes, related to chronic hyperglycaemia, but
      probably also defects in insulin action in the brain. To elucidate the specific
      role of brain insulin signalling in neuronal functions that are relevant for
      cognitive processes we have investigated the behaviour of neurons and synaptic
      plasticity in the hippocampus of mice lacking the insulin receptor substrate
      protein 2 (IRS-2). RESEARCH DESIGN AND METHODS: To study neuronal function and
      synaptic plasticity in the absence of confounding factors such as hyperglycaemia,
      we used a mouse model with a central nervous system- (CNS)-restricted deletion of
      IRS-2 (NesCreIrs2KO). RESULTS: We report a deficit in NMDA receptor-dependent
      synaptic plasticity in the hippocampus of NesCreIrs2KO mice, with a concomitant
      loss of metaplasticity, the modulation of synaptic plasticity by the previous
      activity of a synapse. These plasticity changes are associated with reduced basal
      phosphorylation of the NMDA receptor subunit NR1 and of downstream targets of the
      PI3K pathway, the protein kinases Akt and GSK-3beta. CONCLUSIONS: These findings
      reveal molecular and cellular mechanisms that might underlie cognitive deficits
      linked to specific defects of neuronal insulin signalling.

PMID- 22383999
TI  - Optimizing preprocessing and analysis pipelines for single-subject fMRI: 2.
      Interactions with ICA, PCA, task contrast and inter-subject heterogeneity.
AB  - A variety of preprocessing techniques are available to correct subject-dependant
      artifacts in fMRI, caused by head motion and physiological noise. Although it has
      been established that the chosen preprocessing steps (or "pipeline") may
      significantly affect fMRI results, it is not well understood how preprocessing
      choices interact with other parts of the fMRI experimental design. In this study,
      we examine how two experimental factors interact with preprocessing: between
      subject heterogeneity, and strength of task contrast. Two levels of cognitive
      contrast were examined in an fMRI adaptation of the Trail-Making Test, with data
      from young, healthy adults. The importance of standard preprocessing with motion
      correction, physiological noise correction, motion parameter regression and
      temporal detrending were examined for the two task contrasts. We also tested
      subspace estimation using Principal Component Analysis (PCA), and Independent
      Component Analysis (ICA). Results were obtained for Penalized Discriminant
      Analysis, and model performance quantified with reproducibility (R) and
      prediction metrics (P). Simulation methods were also used to test for potential
      biases from individual-subject optimization. Our results demonstrate that (1)
      individual pipeline optimization is not significantly more biased than fixed
      preprocessing. In addition, (2) when applying a fixed pipeline across all
      subjects, the task contrast significantly affects pipeline performance; in
      particular, the effects of PCA and ICA models vary with contrast, and are not by
      themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline
      for each subject improves within-subject (P,R) and between-subject overlap, with
      the weaker cognitive contrast being more sensitive to pipeline optimization.
      These results demonstrate that sensitivity of fMRI results is influenced not only
      by preprocessing choices, but also by interactions with other experimental design
      factors. This paper outlines a quantitative procedure to denoise data that would
      otherwise be discarded due to artifact; this is particularly relevant for weak
      signal contrasts in single-subject, small-sample and clinical datasets.

PMID- 22384000
TI  - Insights into SCP/TAPS proteins of liver flukes based on large-scale
      bioinformatic analyses of sequence datasets.
AB  - BACKGROUND: SCP/TAPS proteins of parasitic helminths have been proposed to play
      key roles in fundamental biological processes linked to the invasion of and
      establishment in their mammalian host animals, such as the transition from free
      living to parasitic stages and the modulation of host immune responses. Despite
      the evidence that SCP/TAPS proteins of parasitic nematodes are involved in host
      parasite interactions, there is a paucity of information on this protein family
      for parasitic trematodes of socio-economic importance. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted the first large-scale study of SCP/TAPS proteins of a
      range of parasitic trematodes of both human and veterinary importance (including
      the liver flukes Clonorchis sinensis, Opisthorchis viverrini, Fasciola hepatica
      and F. gigantica as well as the blood flukes Schistosoma mansoni, S. japonicum
      and S. haematobium). We mined all current transcriptomic and/or genomic sequence
      datasets from public databases, predicted secondary structures of full-length
      protein sequences, undertook systematic phylogenetic analyses and investigated
      the differential transcription of SCP/TAPS genes in O. viverrini and F. hepatica,
      with an emphasis on those that are up-regulated in the developmental stages
      infecting the mammalian host. CONCLUSIONS: This work, which sheds new light on
      SCP/TAPS proteins, guides future structural and functional explorations of key
      SCP/TAPS molecules associated with diseases caused by flatworms. Future
      fundamental investigations of these molecules in parasites and the integration of
      structural and functional data could lead to new approaches for the control of
      parasitic diseases.

PMID- 22384001
TI  - Variability of NT-proBNP and its relationship with inflammatory status in
      patients with stable essential hypertension: a 2-year follow-up study.
AB  - BACKGROUND: The variability of NT-proBNP levels has been studied in heart
      failure, yet no data exist on these changes over time in hypertensive patients.
      Furthermore, studies on the relationship between natriuretic peptides and
      inflammatory status are limited. METHODOLOGY/PRINCIPAL FINDINGS: 220 clinically
      and functionally asymptomatic stable patients (age 59 +/- 13, 120 male) out of
      252 patients with essential hypertension were followed up, and NT-proBNP was
      measured at baseline, 12 and 24 months. No differences in NT-proBNP were found
      with respect to the basal stage in the hypertrophic group, but significant
      changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP
      measurements was better in patients with hypertrophy than in the non-hypertrophic
      group for the three intervals (stage I-basal; stage II-stage I; stage II-basal)
      with a reference change value of 34%, 35% and 41%, respectively, in the
      hypertrophic group. A more elevated coefficient of correlation was obtained in
      the hypertrophic group than in patients without hypertrophy: basal versus stage I
      (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r =
      0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP
      significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during
      follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an
      independent factor of NT-proBNP. CONCLUSIONS/SIGNIFICANCE: This work shows that
      there is good stability in NT-proBNP levels in a follow-up study of asymptomatic
      patients with stable hypertension and left ventricular hypertrophy. As a
      consequence, assessment of NT-proBNP concentrations may be a useful tool for
      monitoring the follow-up of hypertensive patients with hypertrophy. Measured
      variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a
      24-month follow-up, may indicate an increase in cardiovascular risk, and
      therefore implies adjustment in the medical treatment. In addition, this study
      shows a link between neurohormonal and inflammatory activation in these patients.

PMID- 22384002
TI  - Identification of new genes involved in human adipogenesis and fat storage.
AB  - Since the worldwide increase in obesity represents a growing challenge for health
      care systems, new approaches are needed to effectively treat obesity and its
      associated diseases. One prerequisite for advances in this field is the
      identification of genes involved in adipogenesis and/or lipid storage. To provide
      a systematic analysis of genes that regulate adipose tissue biology and to
      establish a target-oriented compound screening, we performed a high throughput
      siRNA screen with primary (pre)adipocytes, using a druggable siRNA library
      targeting 7,784 human genes. The primary screen showed that 459 genes affected
      adipogenesis and/or lipid accumulation after knock-down. Out of these hits, 333
      could be validated in a secondary screen using independent siRNAs and 110 genes
      were further regulated on the gene expression level during adipogenesis. Assuming
      that these genes are involved in neutral lipid storage and/or adipocyte
      differentiation, we performed InCell-Western analysis for the most striking hits
      to distinguish between the two phenotypes. Beside well known regulators of
      adipogenesis and neutral lipid storage (i.e. PPARgamma, RXR, Perilipin A) the
      screening revealed a large number of genes which have not been previously
      described in the context of fatty tissue biology such as axonemal dyneins. Five
      out of ten axonemal dyneins were identified in our screen and quantitative RT-PCR
      analysis revealed that these genes are expressed in preadipocytes and/or maturing
      adipocytes. Finally, to show that the genes identified in our screen are per se
      druggable we performed a proof of principle experiment using an antagonist for
      HTR2B. The results showed a very similar phenotype compared to knock-down
      experiments proofing the "druggability". Thus, we identified new adipogenesis
      associated genes and those involved in neutral lipid storage. Moreover, by using
      a druggable siRNA library the screen data provides a very attractive starting
      point to identify anti-obesity compounds targeting the adipose tissue.

PMID- 22384003
TI  - The use of nanoscale visible light-responsive photocatalyst TiO2-Pt for the
      elimination of soil-borne pathogens.
AB  - Exposure to the soil-borne pathogens Burkholderia pseudomallei and Burkholderia
      cenocepacia can lead to severe infections and even mortality. These pathogens
      exhibit a high resistance to antibiotic treatments. In addition, no licensed
      vaccine is currently available. A nanoscale platinum-containing titania
      photocatalyst (TiO(2)-Pt) has been shown to have a superior visible light
      responsive photocatalytic ability to degrade chemical contaminants like nitrogen
      oxides. The antibacterial activity of the catalyst and its potential use in soil
      pathogen control were evaluated. Using the plating method, we found that TiO(2)
      Pt exerts superior antibacterial performance against Escherichia coli compared to
      other commercially available and laboratory prepared ultraviolet/visible light
      responsive titania photocatalysts. TiO(2)-Pt-mediated photocatalysis also
      affectively eliminates the soil-borne bacteria B. pseudomallei and B.
      cenocepacia. An air pouch infection mouse model further revealed that TiO(2)-Pt
      mediated photocatalysis could reduce the pathogenicity of both strains of
      bacteria. Unexpectedly, water containing up to 10% w/v dissolved soil particles
      did not reduce the antibacterial potency of TiO(2)-Pt, suggesting that the TiO(2)
      Pt photocatalyst is suitable for use in soil-contaminated environments. The
      TiO(2)-Pt photocatalyst exerted superior antibacterial activity against a broad
      spectrum of human pathogens, including B. pseudomallei and B. cenocepacia. Soil
      particles (<10% w/v) did not significantly reduce the antibacterial activity of
      TiO(2)-Pt in water. These findings suggest that the TiO(2)-Pt photocatalyst may
      have potential applications in the development of bactericides for soil-borne
      pathogens.

PMID- 22384004
TI  - Cardiometabolic risk in US Army recruits and the effects of basic combat
      training.
AB  - BACKGROUND: Cardiometabolic disease risk in US military recruits and the effects
      of military training have not been determined. This study examined lifestyle
      factors and biomarkers associated with cardiometabolic risk in US Army recruits
      (209; 118 male, 91 female, 23 +/- 5 yr) before, during, and after basic combat
      training (BCT). METHODOLOGY/PRINCIPAL FINDINGS: Anthropometrics; fasting total
      (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol; triglycerides (TG); glucose; and insulin were measured at baseline
      and every 3 wks during the 10 wk BCT course. At baseline, 14% of recruits were
      obese (BMI>30 kg/m(2)), 27% were cigarette smokers, 37% were sedentary, and 34%
      reported a family history of cardiometabolic disease. TC was above recommended
      levels in 8%, LDL in 39%, TG in 5%, and glucose in 8% of recruits, and HDL was
      below recommended levels in 33% of recruits at baseline. By week 9, TC decreased
      8%, LDL 10%, TG 13%, glucose 6% and homeostasis model assessment of insulin
      resistance (HOMA-IR) 40% in men (P<0.05). In women, TC, LDL, glucose and HOMA-IR
      were decreased from baseline at weeks 3 and 6 (P<0.05), but were not different
      from baseline levels at week 9. During BCT, body weight declined in men but not
      women, while body fat percentage declined in both men and women (P<0.05).
      CONCLUSIONS/SIGNIFICANCE: At the start of military service, the prevalence of
      cardiometabolic risk in US military recruits is comparable to that reported in
      similar, college-aged populations. Military training appears to be an effective
      strategy that may mitigate risk in young people through improvements in lipid
      profiles and glycemic control.

PMID- 22384005
TI  - Long term sequelae from childhood pneumonia; systematic review and meta-analysis.
AB  - BACKGROUND: The risks of long term sequelae from childhood pneumonia have not
      been systematically assessed. The aims of this study were to: (i) estimate the
      risks of respiratory sequelae after pneumonia in children under five years; (ii)
      estimate the distribution of the different types of respiratory sequelae; and
      (iii) compare sequelae risk by hospitalisation status and pathogen. METHODS: We
      systematically reviewed published papers from 1970 to 2011. Standard global
      burden of disease categories (restrictive lung disease, obstructive lung disease,
      bronchiectasis) were labelled as major sequelae. 'Minor' sequelae (chronic
      bronchitis, asthma, other abnormal pulmonary function, other respiratory
      disease), and multiple impairments were also included. Thirteen papers were
      selected for inclusion. Synthesis was by random effects meta-analysis and meta
      regression. RESULTS: Risk of at least one major sequelae was 5.5% (95% confidence
      interval [95% CI] 2.8-8.3%) in non hospitalised children and 13.6% [6.2-21.1%])
      in hospitalised children. Adenovirus pneumonia was associated with the highest
      sequelae risk (54.8% [39.2-70.5%]) but children hospitalised with no pathogen
      isolated also had high risk (17.6% [10.9-24.3%]). The most common type of major
      sequela was restrictive lung disease (5.4% [2.5-10.2%]) . Potential confounders
      such as loss to follow up and median age at infection were not associated with
      sequelae risk in the final models. CONCLUSIONS: All children with pneumonia
      diagnosed by a health professional should be considered at risk of long term
      sequelae. Evaluation of childhood pneumonia interventions should include
      potential impact on long term respiratory sequelae.

PMID- 22384006
TI  - Neural correlates of visual aesthetics--beauty as the coalescence of stimulus and
      internal state.
AB  - How do external stimuli and our internal state coalesce to create the distinctive
      aesthetic pleasures that give vibrance to human experience? Neuroaesthetics has
      so far focused on the neural correlates of observing beautiful stimuli compared
      to neutral or ugly stimuli, or on neural correlates of judging for beauty as
      opposed to other judgments. Our group questioned whether this approach is
      sufficient. In our view, a brain region that assesses beauty should show beauty
      level-dependent activation during the beauty judgment task, but not during other,
      unrelated tasks. We therefore performed an fMRI experiment in which subjects
      judged visual textures for beauty, naturalness and roughness. Our focus was on
      finding brain activation related to the rated beauty level of the stimuli, which
      would take place exclusively during the beauty judgment. An initial whole-brain
      analysis did not reveal such interactions, yet a number of the regions showing
      main effects of the judgment task or the beauty level of stimuli were selectively
      sensitive to beauty level during the beauty task. Of the regions that were more
      active during beauty judgments than roughness judgments, the frontomedian cortex
      and the amygdala demonstrated the hypothesized interaction effect, while the
      posterior cingulate cortex did not. The latter region, which only showed a task
      effect, may play a supporting role in beauty assessments, such as attending to
      one's internal state rather than the external world. Most of the regions showing
      interaction effects of judgment and beauty level correspond to regions that have
      previously been implicated in aesthetics using different stimulus classes, but
      based on either task or beauty effects alone. The fact that we have now shown
      that task-stimulus interactions are also present during the aesthetic judgment of
      visual textures implies that these areas form a network that is specifically
      devoted to aesthetic assessment, irrespective of the stimulus type.

PMID- 22384007
TI  - The effect of prolonged physical activity performed during extreme caloric
      deprivation on cardiac function.
AB  - BACKGROUND: Endurance exercise may induce transient cardiac dysfunction. Data
      regarding the effect of caloric restriction on cardiac function is limited. We
      studied the effect of physical activity performed during extreme caloric
      deprivation on cardiac function. METHODS: Thirty-nine healthy male soldiers (mean
      age 20 +/- 0.3 years) were studied during a field training exercise lasted 85-103
      hours, with negligible food intake and unlimited water supply. Anthropometric
      measurements, echocardiographic examinations and blood and urine tests were
      performed before and after the training exercise. RESULTS: Baseline VO(2) max was
      59 +/- 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 +/- 0.9 kg.
      There was an increase in plasma urea (11.6 +/- 2.6 to 15.8 +/- 3.8 mmol/L,
      p<0.001) and urine osmolarity (692 +/- 212 to 1094 +/- 140 mmol/kg, p<0.001) and
      a decrease in sodium levels (140.5 +/- 1.0 to 136.6 +/- 2.1 mmol/L, p<0.001) at
      the end of the study. Significant alterations in diastolic parameters included a
      decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A
      and E/E' ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms,
      p = 0.006). There was no change in left or right ventricular systolic function,
      or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were
      significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no
      elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction
      correlated with sodium levels and weight reduction (R = 0.8, p<0.001).
      CONCLUSIONS: Exposure to prolonged physical activity performed under caloric
      deprivation resulted in minor alterations of left ventricular diastolic function.
      BNP levels were significantly reduced due to negative water and sodium balance.

PMID- 22384009
TI  - Growth, development and temporal variation in the onset of six Chironex fleckeri
      medusae seasons: a contribution to understanding jellyfish ecology.
AB  - Despite the worldwide distribution, toxicity and commercial, industrial and
      medical impacts jellyfish present, many aspects of their ecology remain poorly
      understood. Quantified here are important ecological parameters of Chironex
      fleckeri medusae, contributing not only to the understanding of an understudied
      taxon, the cubozoa, but also to the broader understanding of jellyfish ecology.
      C. fleckeri medusae were collected across seven seasons (1999, 2000, 2003, 2005
      07 and 2010), with growth rates, temporal variation in the medusae season onset
      and differences in population structure between estuarine and coastal habitats
      quantified. With a mean of 2 September +/- 2 d (mean +/- 95% confidence limits),
      the earliest date of metamorphosis was temporally constrained between seasons,
      varying by only 7 d (30 August to 5 September). Juvenile medusae appeared to be
      added over an extended period, suggesting polyp metamorphosis was an ongoing
      process once it commenced. At a maximum of 3 +/- 0.2 mm d(-1) IPD, medusae growth
      to an asymptotic size of ~190 mm IPD was rapid, yet, with the oldest medusae
      estimated to be ~78 d in age, medusae did not appear to accumulate along the
      coastline. Furthermore, a greater proportion of juveniles were observed along the
      coastline, with estuarine populations typified by larger medusae. With key
      aspects of C. fleckeri's ecology now quantified, medusae season management
      protocols can be further developed.

PMID- 22384008
TI  - Simultaneous screening of multiple mutations by invader assay improves molecular
      diagnosis of hereditary hearing loss: a multicenter study.
AB  - Although etiological studies have shown genetic disorders to be a common cause of
      congenital/early-onset sensorineural hearing loss, there have been no detailed
      multicenter studies based on genetic testing. In the present report, 264 Japanese
      patients with bilateral sensorineural hearing loss from 33 ENT departments
      nationwide participated. For these patients, we first applied the Invader assay
      for screening 47 known mutations of 13 known deafness genes, followed by direct
      sequencing as necessary. A total of 78 (29.5%) subjects had at least one deafness
      gene mutation. Mutations were more frequently found in the patients with
      congenital or early-onset hearing loss, i.e., in those with an awareness age of 0
      6 years, mutations were significantly higher (41.8%) than in patients with an
      older age of awareness (16.0%). Among the 13 genes, mutations in GJB2 and SLC26A4
      were mainly found in congenital or early-onset patients, in contrast with
      mitochondrial mutations (12S rRNA m.1555A>G, tRNA(Leu(UUR)) m.3243A>G), which
      were predominantly found in older-onset patients. The present method of
      simultaneous screening of multiple deafness mutations by Invader assay followed
      by direct sequencing will enable us to detect deafness mutations in an efficient
      and practical manner for clinical use.

PMID- 22384010
TI  - De novo lipogenesis in adipose tissue is associated with course of morbid obesity
      after bariatric surgery.
AB  - OBJECTIVE: De novo lipogenesis is involved in fatty acid biosynthesis and could
      be involved in the regulation of the triglyceride storage capacity of adipose
      tissue. However, the association between lipogenic and lipolytic genes and the
      evolution of morbidly obese subjects after bariatric surgery remains unknown. In
      this prospective study we analyze the association between the improvement in the
      morbidly obese patients as a result of bariatric surgery and the basal expression
      of lipogenic and lipolytic genes. METHODS: We study 23 non diabetic morbidly
      obese patients who were studied before and 7 months after bariatric surgery.
      Also, we analyze the relative basal mRNA expression levels of lipogenic and
      lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal
      subcutaneous adipose tissue (SAT). RESULTS: When the basal acetyl-CoA carboxylase
      1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression
      in SAT was below percentile-50, there was a greater decrease in weight (P =
      0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034)
      and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery.
      In VAT, when the basal ACSS2 expression was below percentile-50, there was a
      greater decrease in hip circumference (P = 0.006). After adjusting for
      confounding variables in logistic regression models, only the morbidly obese
      patients with SAT or VAT ACSS2 expression >= P50 before bariatric surgery had a
      lower percentage hip circumference loss (<P50) after bariatric surgery (SAT: P =
      0.039; VAT: P = 0.033). CONCLUSIONS: A lower basal ACSS2, ACC1 and ACL
      expression, genes involved in de novo lipogenesis, is associated with a better
      evolution of anthropometric variables after bariatric surgery. Thus, the previous
      state of the pathways involved in fatty acid metabolism may have repercussions on
      the improvement of these patients.

PMID- 22384011
TI  - PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with
      preserved left ventricular function.
AB  - BACKGROUND: Platelet-derived chemokines are implicated in several aspects of
      vascular biology. However, for the chemokine platelet factor 4 variant (PF
      4var/CXCL4L1), released by platelets during thrombosis and with different
      properties as compared to PF-4/CXCL4, its role in heart disease is not yet
      studied. We evaluated the determinants and prognostic value of the platelet
      derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary
      artery disease (CAD). METHODOLOGY/PRINCIPAL FINDINGS: From 205 consecutive
      patients with stable CAD and preserved left ventricular (LV) function, blood
      samples were taken at inclusion and were analyzed for PF-4var, RANTES, platelet
      factor-4 and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Patients were
      followed (median follow-up 2.5 years) for the combined endpoint of cardiac death,
      non-fatal acute myocardial infarction, stroke or hospitalization for heart
      failure. Independent determinants of PF-4var levels (median 10 ng/ml;
      interquartile range 8-16 ng/ml) were age, gender and circulating platelet number.
      Patients who experienced cardiac events (n = 20) during follow-up showed lower
      levels of PF-4var (8.5 [5.3-10] ng/ml versus 12 [8-16] ng/ml, p = 0.033). ROC
      analysis for events showed an area under the curve (AUC) of 0.82 (95% CI 0.73
      0.90, p<0.001) for higher NT-proBNP levels and an AUC of 0.32 (95% CI 0.19-0.45,
      p = 0.009) for lower PF-4var levels. Cox proportional hazard analysis showed that
      PF-4var has an independent prognostic value on top of NT-proBNP. CONCLUSIONS: We
      conclude that low PF-4var/CXCL4L1 levels are associated with a poor outcome in
      patients with stable CAD and preserved LV function. This prognostic value is
      independent of NT-proBNP levels, suggesting that both neurohormonal and platelet
      related factors determine outcome in these patients.

PMID- 22384012
TI  - Visualization of murine intranasal dosing efficiency using luminescent
      Francisella tularensis: effect of instillation volume and form of anesthesia.
AB  - Intranasal instillation is a widely used procedure for pneumonic delivery of
      drugs, vaccine candidates, or infectious agents into the respiratory tract of
      research mice. However, there is a paucity of published literature describing the
      efficiency of this delivery technique. In this report we have used the murine
      model of tularemia, with Francisella tularensis live vaccine strain (FTLVS)
      infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing
      performed either with differing instillation volumes or different types of
      anesthesia. FTLVS was rendered luminescent via transformation with a reporter
      plasmid that constitutively expressed the Photorhabdus luminescens lux operon
      from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging
      system to visualize FT dissemination at various time points following intranasal
      instillation. We found that instillation of FT in a dose volume of 10 ul
      routinely resulted in infection of the upper airways but failed to initiate
      infection of the pulmonary compartment. Efficient delivery of FT into the lungs
      via intranasal instillation required a dose volume of 50 ul or more. These
      studies also demonstrated that intranasal instillation was significantly more
      efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with
      inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The
      collective results underscore the need for researchers to consider both the dose
      volume and the anesthesia type when either performing pneumonic delivery via
      intranasal instillation, or when comparing studies that employed this technique.

PMID- 22384013
TI  - Higher plant cytochrome b5 polypeptides modulate fatty acid desaturation.
AB  - BACKGROUND: Synthesis of polyunsaturated fatty acids (PUFAs) in the endoplasmic
      reticulum of plants typically involves the fatty acid desaturases FAD2 and FAD3,
      which use cytochrome b(5) (Cb5) as an electron donor. Higher plants are reported
      to have multiple isoforms of Cb5, in contrast to a single Cb5 in mammals and
      yeast. Despite the wealth of information available on the roles of FAD2 and FAD3
      in PUFA synthesis, information regarding the contributions of various Cb5
      isoforms in desaturase-mediated reactions is limited. RESULTS: The present
      functional characterization of Cb5 polypeptides revealed that all Arabidopsis Cb5
      isoforms are not similarly efficient in omega-6 desaturation, as evidenced by
      significant variation in their product outcomes in yeast-based functional assays.
      On the other hand, characterization of Cb5 polypeptides of soybean (Glycine max)
      suggested that similar omega-6 desaturation efficiencies were shared by various
      isoforms. With regard to omega-3 desaturation, certain Cb5 genes of both
      Arabidopsis and soybean were shown to facilitate the accumulation of more
      desaturation products than others when co-expressed with their native FAD3.
      Additionally, similar trends of differential desaturation product accumulation
      were also observed with most Cb5 genes of both soybean and Arabidopsis even if co
      expressed with non-native FAD3. CONCLUSIONS: The present study reports the first
      description of the differential nature of the Cb5 genes of higher plants in fatty
      acid desaturation and further suggests that omega-3/omega-6 desaturation product
      outcome is determined by the nature of both the Cb5 isoform and the fatty acid
      desaturases.

PMID- 22384014
TI  - Environmental factors affecting large-bodied coral reef fish assemblages in the
      Mariana Archipelago.
AB  - Large-bodied reef fishes represent an economically and ecologically important
      segment of the coral reef fish assemblage. Many of these individuals supply the
      bulk of the reproductive output for their population and have a disproportionate
      effect on their environment (e.g. as apex predators or bioeroding herbivores).
      Large-bodied reef fishes also tend to be at greatest risk of overfishing, and
      their loss can result in a myriad of either cascading (direct) or indirect
      trophic and other effects. While many studies have investigated habitat
      characteristics affecting populations of small-bodied reef fishes, few have
      explored the relationship between large-bodied species and their environment.
      Here, we describe the distribution of the large-bodied reef fishes in the Mariana
      Archipelago with an emphasis on the environmental factors associated with their
      distribution. Of the factors considered in this study, a negative association
      with human population density showed the highest relative influence on the
      distribution of large-bodied reef fishes; however, depth, water temperature, and
      distance to deep water also were important. These findings provide new
      information on the ecology of large-bodied reef fishes can inform discussions
      concerning essential fish habitat and ecosystem-based management for these
      species and highlight important knowledge gaps worthy of additional research.

PMID- 22384015
TI  - Carbinolamine formation and dehydration in a DNA repair enzyme active site.
AB  - In order to suggest detailed mechanistic hypotheses for the formation and
      dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer
      glycosylase (T4PDG) reaction, we have investigated these reactions using steered
      molecular dynamics with a coupled quantum mechanics-molecular mechanics potential
      (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation
      with and without a water molecule restrained to remain within the active site
      quantum region. We recovered potentials of mean force (PMF) from thirty replicate
      reaction trajectories using Jarzynski averaging. We demonstrated feasible
      pathways involving water, as well as those independent of water participation.
      The water-independent enzyme-catalyzed reaction had a bias-corrected Jarzynski
      average barrier height of approximately (6.5 kcal mol(-1) (27.2 kJ mol(-1)) for
      the carbinolamine formation reaction and 44.5 kcal mol(-1) (186 kJ mol(-1)) for
      the reverse reaction at this level of representation. When the proton transfer
      was facilitated with an intrinsic quantum water, the barrier height was
      approximately 15 kcal mol(-1) (62.8 kJ mol(-1)) in the forward (formation)
      reaction and 19 kcal mol(-1) (79.5 kJ mol(-1)) for the reverse. In addition, two
      modes of unsteered (free dynamics) carbinolamine dehydration were observed: in
      one, the quantum water participated as an intermediate proton transfer species,
      and in the other, the active site protonated glutamate hydrogen was directly
      transferred to the carbinolamine oxygen. Water-independent unforced proton
      transfer from the protonated active site glutamate carboxyl to the unprotonated N
      terminal amine was also observed. In summary, complex proton transfer events,
      some involving water intermediates, were studied in QM/MM simulations of T4PDG
      bound to a DNA abasic site. Imine carbinolamine formation was characterized using
      steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate
      to form the final imine product was observed in free, unsteered, QM/MM dynamics
      simulations, as was unforced acid-base transfer between the active site
      carboxylate and the N-terminal amine.

PMID- 22384016
TI  - Assessment of metagenomic assembly using simulated next generation sequencing
      data.
AB  - Due to the complexity of the protocols and a limited knowledge of the nature of
      microbial communities, simulating metagenomic sequences plays an important role
      in testing the performance of existing tools and data analysis methods with
      metagenomic data. We developed metagenomic read simulators with platform-specific
      (Sanger, pyrosequencing, Illumina) base-error models, and simulated metagenomes
      of differing community complexities. We first evaluated the effect of rigorous
      quality control on Illumina data. Although quality filtering removed a large
      proportion of the data, it greatly improved the accuracy and contig lengths of
      resulting assemblies. We then compared the quality-trimmed Illumina assemblies to
      those from Sanger and pyrosequencing. For the simple community (10 genomes) all
      sequencing technologies assembled a similar amount and accurately represented the
      expected functional composition. For the more complex community (100 genomes)
      Illumina produced the best assemblies and more correctly resembled the expected
      functional composition. For the most complex community (400 genomes) there was
      very little assembly of reads from any sequencing technology. However, due to the
      longer read length the Sanger reads still represented the overall functional
      composition reasonably well. We further examined the effect of scaffolding of
      contigs using paired-end Illumina reads. It dramatically increased contig lengths
      of the simple community and yielded minor improvements to the more complex
      communities. Although the increase in contig length was accompanied by increased
      chimericity, it resulted in more complete genes and a better characterization of
      the functional repertoire. The metagenomic simulators developed for this research
      are freely available.

PMID- 22384017
TI  - Disparate impact of butyroyloxymethyl diethylphosphate (AN-7), a histone
      deacetylase inhibitor, and doxorubicin in mice bearing a mammary tumor.
AB  - The histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN
      7) synergizes the cytotoxic effect of doxorubicin (Dox) and anti-HER2 on mammary
      carcinoma cells while protecting normal cells against their insults. This study
      investigated the concomitant changes occurring in heart tissue and tumors of mice
      bearing a subcutaneous 4T1 mammary tumor following treatment with AN-7, Dox, or
      their combination. Dox or AN-7 alone led to inhibition of both tumor growth and
      lung metastases, whereas their combination significantly increased their
      anticancer efficacy and attenuated Dox- toxicity. Molecular analysis revealed
      that treatment with Dox, AN-7, and to a greater degree, AN-7 together with Dox
      increased tumor levels of gammaH2AX, the marker for DNA double-strand breaks and
      decreased the expression of Rad51, a protein needed for DNA repair. These events
      culminated in increased apoptosis, manifested by the appearance of cytochrome-c
      in the cytosol. In the myocardium, Dox-induced cardiomyopathy was associated with
      an increase in gammaH2AX expression and a reduction in Rad51 and MRE11 expression
      and increased apoptosis. The addition of AN-7 to the Dox treatment protected the
      heart from Dox insults as was manifested by a decrease in gammaH2AX levels, an
      increase in Rad51 and MRE11 expression, and a diminution of cytochrome-c release.
      Tumor fibrosis was high in untreated mice but diminished in Dox- and AN-7-treated
      mice and was almost abrogated in AN-7+Dox-treated mice. By contrast, in the
      myocardium, Dox alone induced a dramatic increase in fibrosis, and AN7+Dox
      attenuated it. The high expression levels of c-Kit, Ki-67, c-Myc, lo-FGF, and
      VEGF in 4T1 tumors were significantly reduced by Dox or AN-7 and further
      attenuated by AN-7+Dox. In the myocardium, Dox suppressed these markers, whereas
      AN-7+Dox restored their expression. In conclusion, the combination of AN-7 and
      Dox results in two beneficial effects, improved anticancer efficacy and
      cardioprotection.

PMID- 22384018
TI  - Evaluating characteristics of de novo assembly software on 454 transcriptome
      data: a simulation approach.
AB  - BACKGROUND: The quantity of transcriptome data is rapidly increasing for non
      model organisms. As sequencing technology advances, focus shifts towards solving
      bioinformatic challenges, of which sequence read assembly is the first task.
      Recent studies have compared the performance of different software to establish a
      best practice for transcriptome assembly. Here, we adapted a simulation approach
      to evaluate specific features of assembly programs on 454 data. The novelty of
      our study is that the simulation allows us to calculate a model assembly as
      reference point for comparison. FINDINGS: The simulation approach allows us to
      compare basic metrics of assemblies computed by different software applications
      (CAP3, MIRA, Newbler, and Oases) to a known optimal solution. We found MIRA and
      CAP3 are conservative in merging reads. This resulted in comparably high number
      of short contigs. In contrast, Newbler more readily merged reads into longer
      contigs, while Oases produced the overall shortest assembly. Due to the
      simulation approach, reads could be traced back to their correct placement within
      the transcriptome. Together with mapping reads onto the assembled contigs, we
      were able to evaluate ambiguity in the assemblies. This analysis further
      supported the conservative nature of MIRA and CAP3, which resulted in low
      proportions of chimeric contigs, but high redundancy. Newbler produced less
      redundancy, but the proportion of chimeric contigs was higher. CONCLUSION: Our
      evaluation of four assemblers suggested that MIRA and Newbler slightly
      outperformed the other programs, while showing contrasting characteristics. Oases
      did not perform very well on the 454 reads. Our evaluation indicated that the
      software was either conservative (MIRA) or liberal (Newbler) about merging reads
      into contigs. This suggested that in choosing an assembly program researchers
      should carefully consider their follow up analysis and consequences of the chosen
      approach to gain an assembly.

PMID- 22384019
TI  - Evidence of latitudinal migration in tri-colored bats, Perimyotis subflavus.
AB  - BACKGROUND: Annual movements of tri-colored bats (Perimyotis subflavus) are
      poorly understood. While this species has been considered a regional migrant,
      some evidence suggests that it may undertake annual latitudinal migrations,
      similar to other long distance North American migratory bat species.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated migration in P. subflavus by
      conducting stable hydrogen isotope analyses of 184 museum specimen fur samples
      and comparing these results (deltaD(fur)) to published interpolated deltaD values
      of collection site growing season precipitation (deltaD(precip)). Results suggest
      that the male molt period occurred between June 23 and October 16 and 33% of
      males collected during the presumed non-molt period were south of their location
      of fur growth. For the same time period, 16% of females were south of their
      location of fur growth and in general, had not travelled as far as migratory
      males. There were strong correlations between deltaD(fur) from the presumed molt
      period and both growing season deltaD(precip) (males--r(2) = 0.86; p<0.01;
      females--r(2) = 0.75; p < 0.01), and latitude of collection (males--r(2) = 0.85;
      p<0.01; females--r(2) = 0.73; p<0.01). Most migrants were collected at the
      northern (>40  degrees N; males and females) and southern (<35  degrees N; males
      only) extents of the species' range. CONCLUSIONS/SIGNIFICANCE: These results
      indicate a different pattern of migration for this species than previously
      documented, suggesting that some P. subflavus engage in annual latitudinal
      migrations and that migratory tendency varies with latitude and between sexes. We
      suggest that this species' hibernation ecology makes it particularly susceptible
      to long winters, making migration from the northern extent of the species' range
      to more southern hibernacula preferable for some individuals. Fur deltaD values
      for some of the northern individuals may indicate an increase in the currently
      accepted northern range of this species. Sex-biased differences in migration may
      be the result of differences in reproductive pressures.

PMID- 22384020
TI  - Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in
      breast cancer cells.
AB  - OBJECTIVE: Trastuzumab has been used for the treatment of HER2-positive breast
      cancer (BC). However, a subset of BC patients exhibited resistance to trastuzumab
      therapy. Thus, clarifying the molecular mechanism of trastuzumab treatment will
      be beneficial to improve the treatment of HER2-positive BC patients. In this
      study, we identified trastuzumab-responsive microRNAs that are involved in the
      therapeutic effects of trastuzumab. METHODS AND RESULTS: RNA samples were
      obtained from HER2-positive (SKBR3 and BT474) and HER2-negetive (MCF7 and MDA-MB
      231) cells with and without trastuzumab treatment for 6 days. Next, we conducted
      a microRNA profiling analysis using these samples to screen those microRNAs that
      were up- or down-regulated only in HER2-positive cells. This analysis identified
      miR-26a and miR-30b as trastuzumab-inducible microRNAs. Transfecting miR-26a and
      miR-30b induced cell growth suppression in the BC cells by 40% and 32%,
      respectively. A cell cycle analysis showed that these microRNAs induced G1 arrest
      in HER2-positive BC cells as trastuzumab did. An Annexin-V assay revealed that
      miR-26a but not miR-30b induced apoptosis in HER2-positive BC cells. Using the
      prediction algorithms for microRNA targets, we identified cyclin E2 (CCNE2) as a
      target gene of miR-30b. A luciferase-based reporter assay demonstrated that miR
      30b post-transcriptionally reduced 27% (p = 0.005) of the gene expression by
      interacting with two binding sites in the 3'-UTR of CCNE2. CONCLUSION: In BC
      cells, trastuzumab modulated the expression of a subset of microRNAs, including
      miR-26a and miR-30b. The upregulation of miR-30b by trastuzumab may play a
      biological role in trastuzumab-induced cell growth inhibition by targeting CCNE2.

PMID- 22384021
TI  - In vitro study of novel collagenase (XIAFLEX(r)) on Dupuytren's disease
      fibroblasts displays unique drug related properties.
AB  - Dupuytren's disease (DD) is a benign, fibroproliferative disease of the palmar
      fascia, with excessive extracellular matrix (ECM) deposition and over-production
      of cytokines and growth factors, resulting in digital fixed flexion contractures
      limiting hand function and patient quality of life. Surgical fasciectomy is the
      gold standard treatment but is invasive and has associated morbidity without
      limiting disease recurrence. Injectable Collagenase Clostridium histolyticum
      (CCH)--Xiaflex(r)--is a novel, nonsurgical option with clinically proven in vivo
      reduction of DD contractures but with limited in vitro data demonstrating its
      cellular and molecular effects. The aim of this study was to delineate the
      effects of CCH on primary fibroblasts isolated from DD and non-DD anatomical
      sites (using RTCA, LDH, WST-1, FACS, qRT-PCR, ELISA and In-Cell Quantitative
      Western Blotting) to compare the efficacy of varying concentrations of Xiaflex(r)
      against a reagent grade Collagenase, Collagenase A. Results demonstrated that DD
      nodule and cord fibroblasts had greater proliferation than those from fat and
      skin. Xiaflex(r) exposure resulted in dose- and time-dependent inhibition of
      cellular spreading, attachment and proliferation, with cellular recovery after
      enzyme removal. Unlike Collagenase A, Xiaflex(r) did not cause apoptosis.
      Collagen expression patterns were significantly (p<0.05) different in DD
      fibroblasts across anatomical sites - the highest levels of collagen I and III
      were detected in DD nodule, with DD cord and fat fibroblasts demonstrating a
      smaller increase in both collagen expression relative to DD skin. Xiaflex(r)
      significantly (p<0.05) down-regulated ECM components, cytokines and growth
      factors in a dose-dependent manner. An in vitro scratch wound assay model
      demonstrated that, at low concentrations, Xiaflex(r) enabled a faster fibroblast
      reparatory migration into the wound, whereas, at high concentrations, this
      process was significantly (p<0.05) inhibited. This is the first report
      elucidating potential mechanisms of action of Xiaflex(r) on Dupuytren
      fibroblasts, offering a greater insight and a better understanding of its effect
      in DD.

PMID- 22384022
TI  - Isothermal amplification using a chemical heating device for point-of-care
      detection of HIV-1.
AB  - BACKGROUND: To date, the use of traditional nucleic acid amplification tests
      (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory
      settings due to time, equipment, and technical expertise requirements. The
      availability of a rapid NAAT with applicability for resource-limited or point-of
      care (POC) settings would fill a great need in HIV diagnostics, allowing for
      timely diagnosis or confirmation of infection status, as well as facilitating the
      diagnosis of acute infection, screening and evaluation of infants born to HIV
      infected mothers. Isothermal amplification methods, such as reverse
      transcription, loop-mediated isothermal amplification (RT-LAMP), exhibit
      characteristics that are ideal for POC settings, since they are typically
      quicker, easier to perform, and allow for integration into low-tech, portable
      heating devices. METHODOLOGY/SIGNIFICANT FINDINGS: In this study, we evaluated
      the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid
      amplification (NINA) heating devices that generate heat from the exothermic
      reaction of calcium oxide and water. The NINA heating devices exhibited stable
      temperatures throughout the amplification reaction and consistent amplification
      results between three separate devices and a thermalcycler. The performance of
      the NINA heaters was validated using whole blood specimens from HIV-1 infected
      patients. CONCLUSION: The RT-LAMP isothermal amplification method used in
      conjunction with a chemical heating device provides a portable, rapid and robust
      NAAT platform that has the potential to facilitate HIV-1 testing in resource
      limited settings and POC.

PMID- 22384023
TI  - Attenuating effect of vigorous physical activity on the risk for inherited
      obesity: a study of 47,691 runners.
AB  - OBJECTIVE: Physical activity has been shown to attenuate the effect of the FTO
      polymorphism on body weight, and the heritability of body weight in twin and in
      family studies. The dose-response relationship between activity and the risk for
      inherited obesity is not well known, particularly for higher doses of vigorous
      exercise. Such information is needed to best prescribe an exercise dose for
      obesity prevention in those at risk due to their family history. DESIGN: We
      therefore analyzed self-reported usual running distance, body mass index (BMI),
      waist circumference, and mother's and father's adiposity (1 = lean, 2 = normal, 3
      = overweight, and 4 = very overweight) from survey data collected on 33,480 male
      and 14,211 female runners. Age-, education-, and alcohol-adjusted regression
      analyses were used to estimate the contribution of parental adiposities to the
      BMI and waist circumferences in runners who ran an average of <3, 3-6, 6-9, >= 9
      km/day. RESULTS: BMI and waist circumferences of runners who ran <3 km/day were
      significantly related to their parents adiposity (P<10(-15) and P<10(-11),
      respectively). These relationships (i.e., kg/m(2) or cm per increment in parental
      adiposity) diminished significantly with increasing running distance for both BMI
      (inheritance*exercise interaction, males: P<10(-10); females: P<10(-5)) and waist
      circumference (inheritance * exercise interaction, males: P<10(-9); females: P =
      0.004). Compared to <3 km/day, the parental contribution to runners who averaged
      >= 9 km/day was diminished by 48% for male BMI, 58% for female BMI, 55% for male
      waist circumference, and 58% for female waist circumference. These results could
      not be attributed to self-selection. CONCLUSIONS: Exceeding the minimum exercise
      dose currently recommended for general health benefits (energy equivalent to
      running 2-3 km/day) may substantially diminish the risk for inherited obesity.
      The results are consistent with other research suggesting the physical activity
      dose required to prevent unhealthy weight gain is greater than that recommended
      for other health benefits.

PMID- 22384024
TI  - Protein-protein interactions in clathrin vesicular assembly: radial distribution
      of evolutionary constraints in interfaces.
AB  - In eukaryotic organisms clathrin-coated vesicles are instrumental in the
      processes of endocytosis as well as intracellular protein trafficking. Hence, it
      is important to understand how these vesicles have evolved across eukaryotes, to
      carry cargo molecules of varied shapes and sizes. The intricate nature and
      functional diversity of the vesicles are maintained by numerous interacting
      protein partners of the vesicle system. However, to delineate functionally
      important residues participating in protein-protein interactions of the assembly
      is a daunting task as there are no high-resolution structures of the intact
      assembly available. The two cryoEM structures closely representing intact
      assembly were determined at very low resolution and provide positions of Calpha
      atoms alone. In the present study, using the method developed by us earlier, we
      predict the protein-protein interface residues in clathrin assembly, taking
      guidance from the available low-resolution structures. The conservation status of
      these interfaces when investigated across eukaryotes, revealed a radial
      distribution of evolutionary constraints, i.e., if the members of the clathrin
      vesicular assembly can be imagined to be arranged in spherical manner, the cargo
      being at the center and clathrins being at the periphery, the detailed
      phylogenetic analysis of these members of the assembly indicated high-residue
      variation in the members of the assembly closer to the cargo while high
      conservation was noted in clathrins and in other proteins at the periphery of the
      vesicle. This points to the strategy adopted by the nature to package diverse
      proteins but transport them through a highly conserved mechanism.

PMID- 22384025
TI  - Thioredoxin glutathione reductase as a novel drug target: evidence from
      Schistosoma japonicum.
AB  - BACKGROUND: Schistosomiasis remains a major public health concern affecting
      billions of people around the world. Currently, praziquantel is the only drug of
      choice for treatment of human schistosomiasis. The emergence of drug resistance
      to praziquantel in schistosomes makes the development of novel drugs an urgent
      task. Thioredoxin glutathione reductase (TGR) enzymes in Schistosoma mansoni and
      some other platyhelminths have been identified as alternative targets. The
      present study was designed to confirm the existense and the potential value of
      TGR as a target for development of novel antischistosomal agents in Schistosoma
      japonicum, a platyhelminth endemic in Asia. METHODS AND FINDINGS: After cloning
      the S. japonicum TGR (SjTGR) gene, the recombinant SjTGR selenoprotein was
      purified and characterized in enzymatic assays as a multifunctional enzyme with
      thioredoxin reductase (TrxR), glutathione reductase (GR) and glutaredoxin (Grx)
      activities. Immunological and bioinformatic analyses confirmed that instead of
      having separate TrxR and GR proteins in mammalian, S. japonicum only encodes TGR,
      which performs the functions of both enzymes and plays a critical role in
      maintaining the redox balance in this parasite. These results were in good
      agreement with previous findings in Schistosoma mansoni and some other
      platyhelminths. Auranofin, a known inhibitor against TGR, caused fatal toxicity
      in S. japonicum adult worms in vitro and reduced worm and egg burdens in S.
      japonicum infected mice. CONCLUSIONS: Collectively, our study confirms that a
      multifunctional enzyme SjTGR selenoprotein, instead of separate TrxR and GR
      enzymes, exists in S. japonicum. Furthermore, TGR may be a potential target for
      development of novel agents against schistosomes. This assumption is strengthened
      by our demonstration that the SjTGR is an essential enzyme for maintaining the
      thiol-disulfide redox homeostasis of S. japonicum.

PMID- 22384026
TI  - Correlation functions quantify super-resolution images and estimate apparent
      clustering due to over-counting.
AB  - We present an analytical method using correlation functions to quantify
      clustering in super-resolution fluorescence localization images and electron
      microscopy images of static surfaces in two dimensions. We use this method to
      quantify how over-counting of labeled molecules contributes to apparent self
      clustering and to calculate the effective lateral resolution of an image. This
      treatment applies to distributions of proteins and lipids in cell membranes,
      where there is significant interest in using electron microscopy and super
      resolution fluorescence localization techniques to probe membrane heterogeneity.
      When images are quantified using pair auto-correlation functions, the magnitude
      of apparent clustering arising from over-counting varies inversely with the
      surface density of labeled molecules and does not depend on the number of times
      an average molecule is counted. In contrast, we demonstrate that over-counting
      does not give rise to apparent co-clustering in double label experiments when
      pair cross-correlation functions are measured. We apply our analytical method to
      quantify the distribution of the IgE receptor (FcepsilonRI) on the plasma
      membranes of chemically fixed RBL-2H3 mast cells from images acquired using
      stochastic optical reconstruction microscopy (STORM/dSTORM) and scanning electron
      microscopy (SEM). We find that apparent clustering of FcepsilonRI-bound IgE is
      dominated by over-counting labels on individual complexes when IgE is directly
      conjugated to organic fluorophores. We verify this observation by measuring pair
      cross-correlation functions between two distinguishably labeled pools of IgE
      FcepsilonRI on the cell surface using both imaging methods. After correcting for
      over-counting, we observe weak but significant self-clustering of IgE-FcepsilonRI
      in fluorescence localization measurements, and no residual self-clustering as
      detected with SEM. We also apply this method to quantify IgE-FcepsilonRI
      redistribution after deliberate clustering by crosslinking with two distinct
      trivalent ligands of defined architectures, and we evaluate contributions from
      both over-counting of labels and redistribution of proteins.

PMID- 22384027
TI  - An improved chloroplast DNA extraction procedure for whole plastid genome
      sequencing.
AB  - BACKGROUND: Chloroplast genomes supply valuable genetic information for
      evolutionary and functional studies in plants. The past five years have witnessed
      a dramatic increase in the number of completely sequenced chloroplast genomes
      with the application of second-generation sequencing technology in plastid genome
      sequencing projects. However, cost-effective high-throughput chloroplast DNA
      (cpDNA) extraction becomes a major bottleneck restricting the application, as
      conventional methods are difficult to make a balance between the quality and
      yield of cpDNAs. METHODOLOGY/PRINCIPAL FINDINGS: We first tested two traditional
      methods to isolate cpDNA from the three species, Oryza brachyantha, Leersia
      japonica and Prinsepia utihis. Both of them failed to obtain properly defined
      cpDNA bands. However, we developed a simple but efficient method based on sucrose
      gradients and found that the modified protocol worked efficiently to isolate the
      cpDNA from the same three plant species. We sequenced the isolated DNA samples
      with Illumina (Solexa) sequencing technology to test cpDNA purity according to
      aligning sequence reads to the reference chloroplast genomes, showing that the
      reference genome was properly covered. We show that 40-50% cpDNA purity is
      achieved with our method. CONCLUSION: Here we provide an improved method used to
      isolate cpDNA from angiosperms. The Illumina sequencing results suggest that the
      isolated cpDNA has reached enough yield and sufficient purity to perform
      subsequent genome assembly. The cpDNA isolation protocol thus will be widely
      applicable to the plant chloroplast genome sequencing projects.

PMID- 22384028
TI  - A genome-wide linkage and association scan reveals novel loci for hypertension
      and blood pressure traits.
AB  - Hypertension is caused by the interaction of environmental and genetic factors.
      The condition which is very common, with about 18% of the adult Hong Kong Chinese
      population and over 50% of older individuals affected, is responsible for
      considerable morbidity and mortality. To identify genes influencing hypertension
      and blood pressure, we conducted a combined linkage and association study using
      over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals
      comprising 111 hypertensive probands and their siblings. Using a family-based
      association test, we found an association with SNPs on chromosome 5q31.1
      (rs6596140; P<9 * 10(-8)) for hypertension. One candidate gene, PDC, was
      replicated, with rs3817586 on 1q31.1 attaining P = 2.5 * 10(-4) and 2.9 * 10(-5)
      in the within-family tests for DBP and MAP, respectively. We also identified
      regions of significant linkage for systolic and diastolic blood pressure on
      chromosomes 2q22 and 5p13, respectively. Further family-based association
      analysis of the linkage peak on chromosome 5 yielded a significant association
      (rs1605685, P<7 * 10(-5)) for DBP. This is the first combined linkage and
      association study of hypertension and its related quantitative traits with
      Chinese ancestry. The associations reported here account for the action of common
      variants whereas the discovery of linkage regions may point to novel targets for
      rare variant screening.

PMID- 22384029
TI  - Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and
      reverses epithelial to mesenchymal transition of mesothelial cells.
AB  - Peritoneal fibrosis is a frequent complication of peritoneal dialysis following
      repeated low grade inflammatory and pro-fibrotic insults. This pathological
      process may lead to ultrafiltration failure and eventually to the discontinuing
      of the therapy. Fibrosis is linked to epithelial to mesenchymal transition (EMT)
      of the peritoneal mesothelial cells, which acquire invasive and fibrogenic
      abilities. Here, we analyzed the role of the transforming growth factor-activated
      kinase-1 (TAK1) in the EMT of primary mesothelial cells from human peritoneum.
      The inhibition of TAK1 in mesenchymal-like mesothelial cells from the effluents
      of patients undergoing peritoneal dialysis led to the reacquisition of the apical
      to basolateral polarity, to increased expression of epithelial and to down
      regulation of mesenchymal markers. TAK1 inhibition also resulted in decreased
      migratory/invasive abilities of effluent-derived mesothelial cells. Simultaneous
      inhibition of ERK1/2 and TAK1 pathways did not lead to an additive effect in the
      reacquisition of the epithelial phenotype. Inhibition of TAK1 also blocked EMT in
      vitro and reduced the levels of PAI-1, which is involved in fibrosis and
      invasion. Analysis of signalling pathways downstream of TAK1 involved in EMT
      induction, showed that TAK1 inhibition reduced the transcriptional activity of NF
      kappaB and Smad3, as well as the phosphorylation of c-jun, while enhancing Smad1
      5-8 activity. These results demonstrate that TAK1 is a cross-point in a network
      including different pro-EMT transcription factors, such as NF-kappaB, Snail, AP-1
      and Smads. The identification of TAK1 as a main biochemical mediator of EMT and
      fibrosis in mesothelial cells from human peritoneum and the study of signalling
      pathways induced by its activity may be relevant in the design of new therapies
      aimed to counteract peritoneal fibrosis.

PMID- 22384030
TI  - Distribution, population biology, and trophic ecology of the deepwater demersal
      fish Halosauropsis macrochir (Pisces: Halosauridae) on the mid-Atlantic Ridge.
AB  - Halosauropsis macrochir ranked amongst the most abundant and widespread demersal
      fishes on the mid-Atlantic Ridge of the North Atlantic (Iceland-Azores) with
      greatest abundance at 1700-3500 m. All sizes, ranging from 10-76 cm total length,
      occurred in the area without any apparent spatial pattern or depth trend. Using
      otolith sections displaying growth increments assumed to represent annuli, the
      age range recorded was 2-36 years, but most individuals were <20 years. Length
      and weight at age data were used to fit growth models. No differences between
      sexes in length and weight at age were observed. The majority of samples had a
      surplus of males. Diet analysis showed that H. macrochir feeds on Crustacea,
      Teleostei, Polychaeta, and Cephalopoda, but few prey could be identified to lower
      taxonomical levels. The mid-Atlantic Ridge constitutes a major portion of the
      North Atlantic living space of the abyssal halosaur where it completes its full
      life cycle, primarily as an actively foraging euryophagous micronekton/epibenthos
      and infauna feeder, becoming a partial piscivore with increasing size.

PMID- 22384031
TI  - GSK3 inhibitor-BIO regulates proliferation of immortalized pancreatic mesenchymal
      stem cells (iPMSCs).
AB  - BACKGROUND: The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen
      synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain
      self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise
      role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth
      and survival is not completely understood at present. RESULTS: To determine
      whether this molecule is involved in controlling the proliferation of iPMSCs, we
      examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by
      BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by
      QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and
      tunel assay. However, we did not find the related roles of BIO on beta cell
      differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin
      release and C-peptide content analysis. CONCLUSIONS: These results suggest that
      BIO plays a key role in the regulation of cell mass proliferation and maintenance
      of the undifferentiated state of iPMSCs.

PMID- 22384033
TI  - Origins of superior dynamic visual acuity in baseball players: superior eye
      movements or superior image processing.
AB  - Dynamic visual acuity (DVA) is defined as the ability to discriminate the fine
      parts of a moving object. DVA is generally better in athletes than in non
      athletes, and the better DVA of athletes has been attributed to a better ability
      to track moving objects. In the present study, we hypothesized that the better
      DVA of athletes is partly derived from better perception of moving images on the
      retina through some kind of perceptual learning. To test this hypothesis, we
      quantitatively measured DVA in baseball players and non-athletes using moving
      Landolt rings in two conditions. In the first experiment, the participants were
      allowed to move their eyes (free-eye-movement conditions), whereas in the second
      they were required to fixate on a fixation target (fixation conditions). The
      athletes displayed significantly better DVA than the non-athletes in the free-eye
      movement conditions. However, there was no significant difference between the
      groups in the fixation conditions. These results suggest that the better DVA of
      athletes is primarily due to an improved ability to track moving targets with
      their eyes, rather than to improved perception of moving images on the retina.

PMID- 22384032
TI  - Neurodegeneration and motor dysfunction in mice lacking cytosolic and
      mitochondrial aldehyde dehydrogenases: implications for Parkinson's disease.
AB  - Previous studies have reported elevated levels of biogenic aldehydes in the
      brains of patients with Parkinson's disease (PD). In the brain, aldehydes are
      primarily detoxified by aldehyde dehydrogenases (ALDH). Reduced ALDH1 expression
      in surviving midbrain dopamine neurons has been reported in brains of patients
      who died with PD. In addition, impaired complex I activity, which is well
      documented in PD, reduces the availability of the NAD(+) co-factor required by
      multiple ALDH isoforms to catalyze the removal of biogenic aldehydes. We
      hypothesized that chronically decreased function of multiple aldehyde
      dehydrogenases consequent to exposure to environmental toxins and/or reduced ALDH
      expression, plays an important role in the pathophysiology of PD. To address this
      hypothesis, we generated mice null for Aldh1a1 and Aldh2, the two isoforms known
      to be expressed in substantia nigra dopamine neurons. Aldh1a1(-/-)*Aldh2(-/-)
      mice exhibited age-dependent deficits in motor performance assessed by gait
      analysis and by performance on an accelerating rotarod. Intraperitoneal
      administration of L-DOPA plus benserazide alleviated the deficits in motor
      performance. We observed a significant loss of neurons immunoreactive for
      tyrosine hydroxylase (TH) in the substantia nigra and a reduction of dopamine and
      metabolites in the striatum of Aldh1a1(-/-)*Aldh2(-/-) mice. We also observed
      significant increases in biogenic aldehydes reported to be neurotoxic, including
      4-hydroxynonenal (4-HNE) and the aldehyde intermediate of dopamine metabolism,
      3,4-dihydroxyphenylacetaldehyde (DOPAL). These results support the hypothesis
      that impaired detoxification of biogenic aldehydes may be important in the
      pathophysiology of PD and suggest that Aldh1a1(-/-)*Aldh2(-/-) mice may be a
      useful animal model of PD.

PMID- 22384034
TI  - Effective interventions and decline of antituberculosis drug resistance in
      Eastern Taiwan, 2004-2008.
AB  - BACKGROUND: The Taiwan health authority recently launched several tuberculosis
      (TB) control interventions, which may have an impact on the epidemic of drug
      resistant TB. We conducted a population-based antituberculosis drug resistance
      surveillance program in Eastern Taiwan to measure the proportions of notified TB
      patients with anti-TB drug resistance and the trend from 2004 to 2008. METHODS
      AND FINDINGS: All culture-positive TB patients were enrolled. Drug susceptibility
      testing results of the first isolate of each TB patient in each treatment course
      were analyzed. In total, 2688 patients were included, of which 2176 (81.0%) were
      new TB cases and 512 (19.0%) were previously treated cases. Among the 2176 new TB
      cases, 97 (4.5%) were retreated after the first episode of TB treatment within
      the study period. The proportion of new patients with any resistance, isoniazid
      resistance but not multidrug-resistant TB (resistant to at least isoniazid and
      rifampin, MDR-TB), and MDR-TB was 16.4%, 7.5%, and 4.0%, respectively, and that
      among previously treated cases was 30.9%, 7.9%, and 17.6%, respectively. The
      combined proportion of any resistance decreased from 23.3% in 2004 to 14.3% in
      2008, and that of MDR-TB from 11.5% to 2.4%. CONCLUSIONS: The proportion of TB
      patients with drug-resistant TB in Eastern Taiwan remains substantial. However,
      an effective TB control program has successfully driven the proportion of drug
      resistance among TB patients downward.

PMID- 22384035
TI  - Comparison of functional proteomic analyses of human breast cancer cell lines
      T47D and MCF7.
AB  - T47D and MCF7 are two human hormone-dependent breast cancer cell lines which are
      widely used as experimental models for in vitro and in vivo (tumor xenografts)
      breast cancer studies. Several proteins involved in cancer development were
      identified in these cell lines by proteomic analyses. Although these studies
      reported the proteomic profiles of each cell line, until now, their differential
      protein expression profiles have not been established. Here, we used two
      dimensional gel and mass spectrometry analyses to compare the proteomic profiles
      of the two cell lines, T47D and MCF7. Our data revealed that more than 164
      proteins are differentially expressed between them. According to their biological
      functions, the results showed that proteins involved in cell growth stimulation,
      anti-apoptosis mechanisms and cancerogenesis are more strongly expressed in T47D
      than in MCF7. These proteins include G1/S-specific cyclin-D3 and prohibitin.
      Proteins implicated in transcription repression and apoptosis regulation,
      including transcriptional repressor NF-X1, nitrilase homolog 2 and interleukin
      10, are, on the contrary, more strongly expressed in MCF7 as compared to T47D.
      Five proteins that were previously described as breast cancer biomarkers, namely
      cathepsin D, cathepsin B, protein S100-A14, heat shock protein beta-1 (HSP27) and
      proliferating cell nuclear antigen (PCNA), are found to be differentially
      expressed in the two cell lines. A list of differentially expressed proteins
      between T47D and MCF7 was generated, providing useful information for further
      studies of breast cancer mechanisms with these cell lines as models.

PMID- 22384036
TI  - Spectrotemporal processing in spectral tuning modules of cat primary auditory
      cortex.
AB  - Spectral integration properties show topographical order in cat primary auditory
      cortex (AI). Along the iso-frequency domain, regions with predominantly narrowly
      tuned (NT) neurons are segregated from regions with more broadly tuned (BT)
      neurons, forming distinct processing modules. Despite their prominent spatial
      segregation, spectrotemporal processing has not been compared for these regions.
      We identified these NT and BT regions with broad-band ripple stimuli and
      characterized processing differences between them using both spectrotemporal
      receptive fields (STRFs) and nonlinear stimulus/firing rate transformations. The
      durations of STRF excitatory and inhibitory subfields were shorter and the best
      temporal modulation frequencies were higher for BT neurons than for NT neurons.
      For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched,
      whereas for BT neurons it was not. Phase locking and feature selectivity were
      higher for NT neurons. Properties of the nonlinearities showed only slight
      differences across the bandwidth modules. These results indicate fundamental
      differences in spectrotemporal preferences--and thus distinct physiological
      functions--for neurons in BT and NT spectral integration modules. However, some
      global processing aspects, such as spectrotemporal interactions and nonlinear
      input/output behavior, appear to be similar for both neuronal subgroups. The
      findings suggest that spectral integration modules in AI differ in what specific
      stimulus aspects are processed, but they are similar in the manner in which
      stimulus information is processed.

PMID- 22384037
TI  - IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion
      in rabbits by preserving the repolarization reserve.
AB  - INTRODUCTION: The function of the repolarization reserve in the prevention of
      ventricular arrhythmias during cardiac ischemia/reperfusion and the impact of
      ischemia on slowly activated delayed rectifier potassium current (I(Ks)) channel
      subunit expression are not well understood. METHODS AND RESULTS: The responses of
      monophasic action potential duration (MAPD) prolongation and triangulation were
      investigated following an L-768,673-induced blockade of I(Ks) with or without
      ischemia/reperfusion in a rabbit model of left circumflex coronary artery
      occlusion/reperfusion. Ischemia/reperfusion and I(Ks) blockade were found to
      significantly induce MAPD90 prolongation and increase triangulation at the
      epicardial zone at 45 min, 60 min, and 75 min after reperfusion, accompanied with
      an increase in premature ventricular beats (PVBs) during the same period.
      Additionally, I(Ks) channel subunit expression was examined following transient
      ischemia or permanent infarction and changes in monophasic action potential (MAP)
      waveforms challenged by beta-adrenergic stimulation were evaluated using a rabbit
      model of transient or chronic cardiac ischemia. The epicardial MAP in the peri
      infarct zone of hearts subjected to infarction for 2 days exhibited increased
      triangulation under adrenergic stimulation. KCNQ1 protein, the alpha subunit of
      the I(Ks) channel, was downregulated in the same group. Both findings were
      consistent with an increased incidence of PVBs. CONCLUSION: Blockade of I(Ks)
      caused MAP triangulation, which precipitated ventricular arrhythmias. Chronic
      ischemia increased the incidence of ventricular arrhythmias under adrenergic
      stimulation and was associated with increased MAP triangulation of the peri
      infarct zone. Downregulation of KCNQ1 protein may be the underlying cause of
      these changes.

PMID- 22384038
TI  - Cognitive control reflects context monitoring, not motoric stopping, in response
      inhibition.
AB  - The inhibition of unwanted behaviors is considered an effortful and controlled
      ability. However, inhibition also requires the detection of contexts indicating
      that old behaviors may be inappropriate--in other words, inhibition requires the
      ability to monitor context in the service of goals, which we refer to as context
      monitoring. Using behavioral, neuroimaging, electrophysiological and
      computational approaches, we tested whether motoric stopping per se is the
      cognitively-controlled process supporting response inhibition, or whether context
      monitoring may fill this role. Our results demonstrate that inhibition does not
      require control mechanisms beyond those involved in context-monitoring, and that
      such control mechanisms are the same regardless of stopping demands. These
      results challenge dominant accounts of inhibitory control, which posit that
      motoric stopping is the cognitively-controlled process of response inhibition,
      and clarify emerging debates on the frontal substrates of response inhibition by
      replacing the centrality of controlled mechanisms for motoric stopping with
      context-monitoring.

PMID- 22384039
TI  - High prevalence of hypertension and placental insufficiency, but no in utero HIV
      transmission, among women on HAART with stillbirths in Botswana.
AB  - BACKGROUND: Increased stillbirth rates occur among HIV-infected women, but no
      studies have evaluated the pathological basis for this increase, or whether
      highly active antiretroviral therapy (HAART) influences the etiology of
      stillbirths. It is also unknown whether HIV infection of the fetus is associated
      with stillbirth. METHODS: HIV-infected women and a comparator group of HIV
      uninfected women who delivered stillbirths were enrolled at the largest referral
      hospital in Botswana between January and November 2010. Obstetrical records,
      including antiretroviral use in pregnancy, were extracted at enrollment. Verbal
      autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and
      placental pathology (blinded to HIV and treatment status) were performed.
      RESULTS: Ninety-nine stillbirths were evaluated, including 62 from HIV-infected
      women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on
      zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a
      comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths
      from HIV-infected women were HIV PCR positive, and both were born to women not
      receiving HAART. Placental insufficiency associated with hypertension accounted
      for most stillbirths. Placental findings consistent with chronic hypertension
      were common among HIV-infected women who received HAART and among HIV-uninfected
      women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not
      receiving HAART (28%, p = 0.003 vs. women on HAART). CONCLUSIONS: In utero HIV
      infection was rarely associated with stillbirths, and did not occur among women
      receiving HAART. Hypertension and placental insufficiency were associated with
      most stillbirths in this tertiary care setting.

PMID- 22384040
TI  - Adherence to antiretroviral treatment and correlation with risk of
      hospitalization among commercially insured HIV patients in the United States.
AB  - PURPOSE: A lower daily pill burden may improve adherence to antiretroviral
      treatment (ART) and clinical outcomes in patients with human immunodeficiency
      virus (HIV). This study assessed differences in adherence using the number of
      pills taken per day, and evaluated how adherence correlated with hospitalization.
      METHODOLOGY: Commercially insured patients in the LifeLink database with an HIV
      diagnosis (International Classification of Diseases, 9th Revision, Clinical
      Modification code 042.xx) between 6/1/2006 and 12/31/2008 and receipt of a
      complete ART regimen were selected for inclusion. Patients were grouped according
      to their daily pill count and remained on ART for at least 60 days. Outcomes
      included adherence and rates of hospitalization. Adherence was measured as the
      proportion of days between the start and end of the regimen in which the patient
      maintained supply of all initiated ART components. Logistic regressions assessed
      the relationship between pills per day, adherence, and hospitalization,
      controlling for demographics, comorbidities, and ART-naive (vs. experienced)
      status. RESULTS: 7,073 patients met the study inclusion criteria, and 33.4%,
      5.8%, and 60.8% received an ART regimen comprising one, two, or three or more
      pills per day, respectively. Regression analysis showed patients receiving a
      single pill per day were significantly more likely to reach a 95% adherence
      threshold versus patients receiving three or more pills per day (odds ratio [OR]
      = 1.59; P<0.001). Regardless of the number of pills received per day, patients
      were over 40% less likely to have a hospitalization if they were adherent to
      therapy (OR = 0.57; P<0.001). Patients receiving a single pill per day were 24%
      less likely to have a hospitalization versus patients receiving three or more
      pills per day (OR = 0.76; P = 0.003). CONCLUSIONS: ART consisting of a single
      pill per day was associated with significantly better adherence and lower risk of
      hospitalization in patients with HIV compared to patients receiving three or more
      pills per day.

PMID- 22384041
TI  - Interleukin-1 stimulates ADAM17 through a mechanism independent of its
      cytoplasmic domain or phosphorylation at threonine 735.
AB  - ADAM17 (a disintegrin and metalloproteinase) is a membrane-anchored
      metalloproteinase that regulates the release of EGFR-ligands, TNFalpha and other
      membrane proteins from cells. ADAM17 can be rapidly activated by a variety of
      signaling pathways, yet little is known about the underlying mechanism. Several
      studies have demonstrated that the cytoplasmic domain of ADAM17 is not required
      for its rapid activation by a variety of stimuli, including phorbol esters,
      tyrosine kinases and some G-protein coupled receptors. However, phosphorylation
      of cytoplasmic residue T735 was recently reported as a crucial step for
      activation of ADAM17 by IL-1beta and by the p38 MAP-kinase pathway. One possible
      mechanism to reconcile these results would be that T735 has an inhibitory role
      and that it must be phosphorylated as a pre-requisite for the activation of
      ADAM17, which would then proceed via a mechanism that is independent of its
      cytoplasmic domain. To test this hypothesis, we performed rescue experiments of
      Adam17-/- cells with wild type and mutant forms of ADAM17. However, these
      experiments showed that an inactivating mutation (T735A) or an activating
      mutation (T735D) of cytoplasmic residue T735 or the removal of the cytoplasmic
      domain of ADAM17 did not significantly affect the stimulation of ADAM17 by IL
      1beta or by activation of MAP-kinase with anisomycin. Moreover, we found that the
      MAP-kinase inhibitor SB203580 blocked activation of cytoplasmic tail-deficient
      ADAM17 and of the T735A mutant by IL-1beta or by anisomycin, providing further
      support for a model in which the activation mechanism of ADAM17 does not rely on
      its cytoplasmic domain or phosphorylation of T735.

PMID- 22384042
TI  - Identification by virtual screening and in vitro testing of human DOPA
      decarboxylase inhibitors.
AB  - Dopa decarboxylase (DDC), a pyridoxal 5'-phosphate (PLP) enzyme responsible for
      the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease
      (PD). PD is a neurodegenerative disease mainly due to a progressive loss of
      dopamine-producing cells in the midbrain. Co-administration of L-Dopa with
      peripheral DDC inhibitors (carbidopa or benserazide) is the most effective
      symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine
      (the in vivo hydrolysis product of benserazide) are both powerful irreversible
      DDC inhibitors, they are not selective because they irreversibly bind to free PLP
      and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of
      this study were (a) to use virtual screening to identify potential human DDC
      inhibitors and (b) to evaluate the reliability of our virtual-screening (VS)
      protocol by experimentally testing the "in vitro" activity of selected molecules.
      Starting from the crystal structure of the DDC-carbidopa complex, a new VS
      protocol, integrating pharmacophore searches and molecular docking, was
      developed. Analysis of 15 selected compounds, obtained by filtering the public
      ZINC database, yielded two molecules that bind to the active site of human DDC
      and behave as competitive inhibitors with K(i) values >=10 uM. By performing in
      silico similarity search on the latter compounds followed by a substructure
      search using the core of the most active compound we identified several
      competitive inhibitors of human DDC with K(i) values in the low micromolar range,
      unable to bind free PLP, and predicted to not cross the blood-brain barrier. The
      most potent inhibitor with a K(i) value of 500 nM represents a new lead compound,
      targeting human DDC, that may be the basis for lead optimization in the
      development of new DDC inhibitors. To our knowledge, a similar approach has not
      been reported yet in the field of DDC inhibitors discovery.

PMID- 22384043
TI  - Exploiting magnetic resonance angiography imaging improves model estimation of
      BOLD signal.
AB  - The change of BOLD signal relies heavily upon the resting blood volume fraction
      ([Formula: see text]) associated with regional vasculature. However, existing
      hemodynamic data assimilation studies pretermit such concern. They simply assign
      the value in a physiologically plausible range to get over ill-conditioning of
      the assimilation problem and fail to explore actual [Formula: see text]. Such
      performance might lead to unreliable model estimation. In this work, we present
      the first exploration of the influence of [Formula: see text] on fMRI data
      assimilation, where actual [Formula: see text] within a given cortical area was
      calibrated by an MR angiography experiment and then was augmented into the
      assimilation scheme. We have investigated the impact of [Formula: see text] on
      single-region data assimilation and multi-region data assimilation (dynamic cause
      modeling, DCM) in a classical flashing checkerboard experiment. Results show that
      the employment of an assumed [Formula: see text] in fMRI data assimilation is
      only suitable for fMRI signal reconstruction and activation detection grounded on
      this signal, and not suitable for estimation of unobserved states and effective
      connectivity study. We thereby argue that introducing physically realistic
      [Formula: see text] in the assimilation process may provide more reliable
      estimation of physiological information, which contributes to a better
      understanding of the underlying hemodynamic processes. Such an effort is valuable
      and should be well appreciated.

PMID- 22384044
TI  - Genome wide adaptations of Plasmodium falciparum in response to lumefantrine
      selective drug pressure.
AB  - The combination therapy of the Artemisinin-derivative Artemether (ART) with
      Lumefantrine (LM) (Coartem(r)) is an important malaria treatment regimen in many
      endemic countries. Resistance to Artemisinin has already been reported, and it is
      feared that LM resistance (LMR) could also evolve quickly. Therefore molecular
      markers which can be used to track Coartem(r) efficacy are urgently needed.
      Often, stable resistance arises from initial, unstable phenotypes that can be
      identified in vitro. Here we have used the Plasmodium falciparum multidrug
      resistant reference strain V1S to induce LMR in vitro by culturing the parasite
      under continuous drug pressure for 16 months. The initial IC(50) (inhibitory
      concentration that kills 50% of the parasite population) was 24 nM. The resulting
      resistant strain V1S(LM), obtained after culture for an estimated 166 cycles
      under LM pressure, grew steadily in 378 nM of LM, corresponding to 15 times the
      IC(50) of the parental strain. However, after two weeks of culturing V1S(LM) in
      drug-free medium, the IC(50) returned to that of the initial, parental strain
      V1S. This transient drug tolerance was associated with major changes in gene
      expression profiles: using the PFSANGER Affymetrix custom array, we identified
      184 differentially expressed genes in V1S(LM). Among those are 18 known and
      putative transporters including the multidrug resistance gene 1 (pfmdr1), the
      multidrug resistance associated protein and the V-type H+ pumping pyrophosphatase
      2 (pfvp2) as well as genes associated with fatty acid metabolism. In addition we
      detected a clear selective advantage provided by two genomic loci in parasites
      grown under LM drug pressure, suggesting that all, or some of those genes
      contribute to development of LM tolerance--they may prove useful as molecular
      markers to monitor P. falciparum LM susceptibility.

PMID- 22384045
TI  - Mechanism-based screen establishes signalling framework for DNA damage-associated
      G1 checkpoint response.
AB  - DNA damage activates checkpoint controls which block progression of cells through
      the division cycle. Several different checkpoints exist that control transit at
      different positions in the cell cycle. A role for checkpoint activation in
      providing resistance of cells to genotoxic anticancer therapy, including
      chemotherapy and ionizing radiation, is widely recognized. Although the core
      molecular functions that execute different damage activated checkpoints are
      known, the signals that control checkpoint activation are far from understood. We
      used a kinome-spanning RNA interference screen to delineate signalling required
      for radiation-mediated retinoblastoma protein activation, the recognized executor
      of G(1) checkpoint control. Our results corroborate the involvement of the p53
      tumour suppressor (TP53) and its downstream targets p21(CIP1/WAF1) but infer lack
      of involvement of canonical double strand break (DSB) recognition known for its
      role in activating TP53 in damaged cells. Instead our results predict signalling
      involving the known TP53 phosphorylating kinase PRPK/TP53RK and the JNK/p38MAPK
      activating kinase STK4/MST1, both hitherto unrecognised for their contribution to
      DNA damage G1 checkpoint signalling. Our results further predict a network
      topology whereby induction of p21(CIP1/WAF1) is required but not sufficient to
      elicit checkpoint activation. Our experiments document a role of the kinases
      identified in radiation protection proposing their pharmacological inhibition as
      a potential strategy to increase radiation sensitivity in proliferating cancer
      cells.

PMID- 22384046
TI  - Dietary fiber and saturated fat intake associations with cardiovascular disease
      differ by sex in the Malmo Diet and Cancer Cohort: a prospective study.
AB  - BACKGROUND: The aim of the study was to examine associations between intake of
      macronutrients and dietary fiber and incident ischemic cardiovascular disease
      (iCVD) in men and women. METHODS: We used data from 8,139 male and 12,535 female
      participants (aged 44-73 y) of the Swedish population-based Malmo Diet and Cancer
      cohort. The participants were without history of CVD and diabetes mellitus, and
      had reported stable dietary habits in the study questionnaire. Diet was assessed
      by a validated modified diet history method, combining a 7-d registration of
      cooked meals and cold beverages, a 168-item food questionnaire (covering other
      foods and meal patterns), and a 1-hour diet interview. Sociodemographic and
      lifestyle data were collected by questionnaire. iCVD cases, which included
      coronary events (myocardial infarctions or deaths from chronic ischemic heart
      disease) and ischemic strokes, were ascertained via national and local
      registries. Nutrient-disease associations were examined by multivariate Cox
      regressions. RESULTS: During a mean follow-up of 13.5 years, we identified 1,089
      male and 687 female iCVD cases. High fiber intakes were associated with lower
      incidence rates of iCVD in women and of ischemic stroke in men. In post-hoc
      analysis, we discovered statistically significant interactions between intake of
      fiber and saturated fat; these interactions also differed between men and women
      (p<0.001). CONCLUSIONS: In this well-defined population, a high fiber intake was
      associated with lower risk of iCVD, but there were no robust associations between
      other macronutrients and iCVD risk. Judging from this study, gender-specific
      nutrient analysis may be preferable in epidemiology.

PMID- 22384047
TI  - Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac
      septal defects in a Han Chinese population.
AB  - BACKGROUND: Clinical research indicates that periconceptional administration of
      folic acid can reduce the occurrence of congenital cardiac septal defects
      (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl
      donor for DNA expression regulation, the de novo biosynthesis of purine and
      pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate
      synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP,
      which is the essential precursor of DNA biosynthesis and repair process. To
      examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we
      investigated whether genetic polymorphisms in the TYMS gene associated with the
      CCSDs in a Han Chinese population. METHOD: Polymorphisms in the noncoding region
      of TYMS were identified via direct sequencing in 32 unrelated individuals
      composed of half CCSDs and half control subjects. Nine SNPs and two
      insertion/deletion polymorphisms were genotyped from two independent case-control
      studies involving a total of 529 CCSDs patients and 876 healthy control
      participants. The associations were examined by both single polymorphism and
      haplotype tests using logistic regression. RESULT: We found that TYMS
      polymorphisms were not related to the altered CCSDs risk, and even to the changed
      risk of VSDs subgroup, when tested in both studied groups separately or in
      combination. In the haplotype analysis, there were no haplotypes significantly
      associated with risks for CCSDs either. CONCLUSION: Our results show no
      association between common genetic polymorphisms of the regulatory region of the
      TYMS gene and CCSDs in the Han Chinese population.

PMID- 22384049
TI  - Measuring empathizing and systemizing with a large US sample.
AB  - A large number of people completed one of two versions of the empathizing
      quotient (EQ) and systemizing quotient (SQ). One version had the negatively
      phrased items all re-worded. These re-worded items were answered more rapidly
      than the original items, and for the SQ produced a more reliable scale. Subjects
      gave self-assessments of empathizing and systemizing, and these were moderately
      correlated, r ~ .6, with their respective quotients. Females had on average
      higher empathizing scores and males had on average higher systemizing scores. If
      a female-male pair was chosen at random, the female would have the higher
      empathizing score about two-thirds of the time, and the males would have the
      higher systemizing score about two-thirds of the time.

PMID- 22384048
TI  - Evidence for altered basal ganglia-brainstem connections in cervical dystonia.
AB  - BACKGROUND: There has been increasing interest in the interaction of the basal
      ganglia with the cerebellum and the brainstem in motor control and movement
      disorders. In addition, it has been suggested that these subcortical connections
      with the basal ganglia may help to coordinate a network of regions involved in
      mediating posture and stabilization. While studies in animal models support a
      role for this circuitry in the pathophysiology of the movement disorder dystonia,
      thus far, there is only indirect evidence for this in humans with dystonia.
      METHODOLOGY/PRINCIPAL FINDINGS: In the current study we investigated
      probabilistic diffusion tractography in DYT1-negative patients with cervical
      dystonia and matched healthy control subjects, with the goal of showing that
      patients exhibit altered microstructure in the connectivity between the pallidum
      and brainstem. The brainstem regions investigated included nuclei that are known
      to exhibit strong connections with the cerebellum. We observed large clusters of
      tractography differences in patients relative to healthy controls, between the
      pallidum and the brainstem. Tractography was decreased in the left hemisphere and
      increased in the right hemisphere in patients, suggesting a potential basis for
      the left/right white matter asymmetry we previously observed in focal dystonia
      patients. CONCLUSIONS/SIGNIFICANCE: These findings support the hypothesis that
      connections between the basal ganglia and brainstem play a role in the
      pathophysiology of dystonia.

PMID- 22384050
TI  - Spatiotemporal variation in avian migration phenology: citizen science reveals
      effects of climate change.
AB  - A growing number of studies have documented shifts in avian migratory phenology
      in response to climate change, and yet there is a large amount of unexplained
      variation in the magnitude of those responses across species and geographic
      regions. We use a database of citizen science bird observations to explore
      spatiotemporal variation in mean arrival dates across an unprecedented geographic
      extent for 18 common species in North America over the past decade, relating
      arrival dates to mean minimum spring temperature. Across all species and
      geographic locations, species shifted arrival dates 0.8 days earlier for every 
      degrees C of warming of spring temperature, but it was common for some species in
      some locations to shift as much as 3-6 days earlier per  degrees C. Species that
      advanced arrival dates the earliest in response to warming were those that
      migrate more slowly, short distance migrants, and species with broader climatic
      niches. These three variables explained 63% of the interspecific variation in
      phenological response. We also identify a latitudinal gradient in the average
      strength of phenological response, with species shifting arrival earlier at
      southern latitudes than northern latitudes for the same degree of warming. This
      observation is consistent with the idea that species must be more phenologically
      sensitive in less seasonal environments to maintain the same degree of precision
      in phenological timing.

PMID- 22384051
TI  - Kin selection and the evolution of social information use in animal conflict.
AB  - Animals often use social information about conspecifics in making decisions about
      cooperation and conflict. While the importance of kin selection in the evolution
      of intraspecific cooperation and conflict is widely acknowledged, few studies
      have examined how relatedness influences the evolution of social information use.
      Here we specifically examine how relatedness affects the evolution of a stylised
      form of social information use known as eavesdropping. Eavesdropping involves
      individuals escalating conflicts with rivals observed to have lost their last
      encounter and avoiding fights with those seen to have won. We use a game
      theoretical model to examine how relatedness affects the evolution of
      eavesdropping, both when strategies are discrete and when they are continuous or
      mixed. We show that relatedness influences the evolution of eavesdropping, such
      that information use peaks at intermediate relatedness. Our study highlights the
      importance of considering kin selection when exploring the evolution of complex
      forms of information use.

PMID- 22384052
TI  - Hybridization but no evidence for backcrossing and introgression in a sympatric
      population of great reed warblers and clamorous reed warblers.
AB  - Hybridization is observed frequently in birds, but often it is not known whether
      the hybrids are fertile and if backcrossing occurs. The breeding ranges of the
      great reed warbler (Acrocephalus arundinaceus) and the clamorous reed warbler (A.
      stentoreus) overlap in southern Kazakhstan and a previous study has documented
      hybridization in a sympatric population. In the present study, we first present a
      large set of novel microsatellite loci isolated and characterised in great reed
      warblers. Secondly, we evaluate whether hybridization in the sympatric breeding
      population has been followed by backcrossing and introgression.We isolated 181
      unique microsatellite loci in great reed warblers. Of 41 loci evaluated, 40
      amplified and 30 were polymorphic. Bayesian clustering analyses based on genotype
      data from 23 autosomal loci recognised two well-defined genetic clusters
      corresponding to the two species. Individuals clustered to a very high extent to
      either of these clusters (admixture proportions >= 0.984) with the exception of
      four previously suggested arundinaceus-stentoreus hybrid birds that showed mixed
      ancestry (admixture proportions 0.495-0.619). Analyses of simulated hybrids and
      backcrossed individuals showed that the sampled birds do not correspond to first
      fourth-generation backcrosses, and that fifth or higher generation backcrosses to
      a high extent resemble 'pure' birds at this set of markers.We conclude that these
      novel microsatellite loci provide a useful molecular resource for Acrocephalus
      warblers. The time to reach reproductive isolation is believed to be very long in
      birds, approximately 5 Myrs, and with an estimated divergence time of 2 Myrs
      between these warblers, some backcrossing and introgression could have been
      expected. However, there was no evidence for backcrossing and introgression
      suggesting that hybrids are either infertile or their progeny inviable. Very low
      levels of introgression cannot be excluded, which still may be an important
      factor as a source of new genetic variation.

PMID- 22384053
TI  - DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for
      studying cellular response to acute ischemia and regeneration.
AB  - Proteomic analysis of myocardial tissue from patient population is suited to
      yield insights into cellular and molecular mechanisms taking place in
      cardiovascular diseases. However, it has been limited by small sized biopsies and
      complicated by high variances between patients. Therefore, there is a high demand
      for suitable model systems with the capability to simulate ischemic and
      cardiotoxic effects in vitro, under defined conditions. In this context, we
      established an in vitro ischemia/reperfusion cardiac disease model based on the
      contractile HL-1 cell line. To identify pathways involved in the cellular
      alterations induced by ischemia and thereby defining disease-specific biomarkers
      and potential target structures for new drug candidates we used fluorescence 2D
      difference gel electrophoresis. By comparing spot density changes in ischemic and
      reperfusion samples we detected several protein spots that were differentially
      abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and
      subsequently grouped by functionality. Most prominent were changes in apoptosis
      signalling, cell structure and energy-metabolism. Alterations were confirmed by
      analysis of human biopsies from patients with ischemic cardiomyopathy.With the
      establishment of our in vitro disease model for ischemia injury target
      identification via proteomic research becomes independent from rare human
      material and will create new possibilities in cardiac research.

PMID- 22384054
TI  - Models analyses for allelopathic effects of chicory at equivalent coupling of
      nitrogen supply and pH level on F. arundinacea, T. repens and M. sativa.
AB  - Alllelopathic potential of chicory was investigated by evaluating its effect on
      seed germination, soluble sugar, malondialdehyde (MDA) and the chlorophyll
      content of three target plants species (Festuca arundinacea, Trifolium repens and
      Medicago sativa). The secretion of allelochemicals was regulated by keeping the
      donor plant (chicory) separate from the three target plant species and using
      different pH and nitrogen levels. Leachates from donor pots with different pH
      levels and nitrogen concentrations continuously irrigated the target pots
      containing the seedlings. The allelopathic effects of the chicory at equivalent
      coupling of nitrogen supply and pH level on the three target plants species were
      explored via models analyses. The results suggested a positive effect of nitrogen
      supply and pH level on allelochemical secretion from chicory plants. The nitrogen
      supply and pH level were located at a rectangular area defined by 149 to 168 mg/l
      nitrogen supply combining 4.95 to 7.0 pH value and point located at nitrogen
      supply 177 mg/l, pH 6.33 when they were in equivalent coupling effects; whereas
      the inhibitory effects of equivalent coupling nitrogen supply and pH level were
      located at rectangular area defined by 125 to 131 mg/l nitrogen supply combining
      6.71 to 6.88 pH value and two points respectively located at nitrogen supply 180
      mg/l with pH 6.38 and nitrogen supply 166 mg/l with pH 7.59. Aqueous extracts of
      chicory fleshy roots and leaves accompanied by treatment at different sand pH
      values and nitrogen concentrations influenced germination, seedling growth,
      soluble sugar, MDA and chlorophyll of F. arundinacea, T. repens and M. sativa.
      Additionally, we determined the phenolics contents of root and leaf aqueous
      extracts, which were 0.104% and 0.044% on average, respectively.

PMID- 22384055
TI  - Investigating the structural impacts of I64T and P311S mutations in APE1-DNA
      complex: a molecular dynamics approach.
AB  - BACKGROUND: Elucidating the molecular dynamic behavior of Protein-DNA complex
      upon mutation is crucial in current genomics. Molecular dynamics approach reveals
      the changes on incorporation of variants that dictate the structure and function
      of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the
      physicochemical property of amino acids that affect the protein stability and
      dynamic behavior. Further, these mutations disrupt the binding sites and prohibit
      the protein to form complexes with its interacting DNA. PRINCIPAL FINDINGS: In
      this study, we developed a rapid and cost-effective method to analyze variants in
      APE1 gene that are associated with disease susceptibility and evaluated their
      impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico
      approaches were used to identify deleterious variants in APE1 gene. Deleterious
      scores that overlap in these approaches were taken in concern and based on it,
      two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further
      for structural analysis. SIGNIFICANCE: Different parameters such as RMSD, RMSF,
      salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that
      predicted deleterious variants I64T and P311S alters the structure as well as
      affect the stability of APE1-DNA interacting functions. This study addresses such
      new methods for validating functional polymorphisms of human APE1 which is
      critically involved in causing deficit in repair capacity, which in turn leads to
      genetic instability and carcinogenesis.

PMID- 22384056
TI  - GUCY2C opposes systemic genotoxic tumorigenesis by regulating AKT-dependent
      intestinal barrier integrity.
AB  - The barrier separating mucosal and systemic compartments comprises epithelial
      cells, annealed by tight junctions, limiting permeability. GUCY2C recently
      emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt
      villus homeostasis. Here, the contribution of GUCY2C to barrier integrity
      opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C
      (Gucy2c(-/-)) exhibited barrier hyperpermeability associated with reduced
      junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier
      permeability associated with increased junctional proteins. Further, silencing
      GUCY2C exacerbated, while activation reduced, chemical barrier disruption and
      colitis. Moreover, eliminating GUCY2C amplified, while activation reduced,
      systemic oxidative DNA damage. This genotoxicity was associated with increased
      spontaneous and carcinogen-induced systemic tumorigenesis in Gucy2c(-/-) mice.
      GUCY2C regulated barrier integrity by repressing AKT1, associated with increased
      junction proteins occludin and claudin 4 in mice and Caco2 cells in vitro. Thus,
      GUCY2C defends the intestinal barrier, opposing colitis and systemic genotoxicity
      and tumorigenesis. The therapeutic potential of this observation is underscored
      by the emerging clinical development of oral GUCY2C ligands, which can be used
      for chemoprophylaxis in inflammatory bowel disease and cancer.

PMID- 22384057
TI  - Gene-based analysis of regionally enriched cortical genes in GWAS data sets of
      cognitive traits and psychiatric disorders.
AB  - BACKGROUND: Despite its estimated high heritability, the genetic architecture
      leading to differences in cognitive performance remains poorly understood.
      Different cortical regions play important roles in normal cognitive functioning
      and impairment. Recently, we reported on sets of regionally enriched genes in
      three different cortical areas (frontomedial, temporal and occipital cortices) of
      the adult rat brain. It has been suggested that genes preferentially, or
      specifically, expressed in one region or organ reflect functional specialisation.
      Employing a gene-based approach to the analysis, we used the regionally enriched
      cortical genes to mine a genome-wide association study (GWAS) of the Norwegian
      Cognitive NeuroGenetics (NCNG) sample of healthy adults for association to nine
      psychometric tests measures. In addition, we explored GWAS data sets for the
      serious psychiatric disorders schizophrenia (SCZ) (n = 3 samples) and bipolar
      affective disorder (BP) (n = 3 samples), to which cognitive impairment is linked.
      PRINCIPAL FINDINGS: At the single gene level, the temporal cortex enriched gene
      RAR-related orphan receptor B (RORB) showed the strongest overall association,
      namely to a test of verbal intelligence (Vocabulary, P = 7.7E-04). We also
      applied gene set enrichment analysis (GSEA) to test the candidate genes, as gene
      sets, for enrichment of association signal in the NCNG GWAS and in GWASs of BP
      and of SCZ. We found that genes differentially expressed in the temporal cortex
      showed a significant enrichment of association signal in a test measure of non
      verbal intelligence (Reasoning) in the NCNG sample. CONCLUSION: Our gene-based
      approach suggests that RORB could be involved in verbal intelligence differences,
      while the genes enriched in the temporal cortex might be important to
      intellectual functions as measured by a test of reasoning in the healthy
      population. These findings warrant further replication in independent samples on
      cognitive traits.

PMID- 22384058
TI  - A novel biochemical route for fuels and chemicals production from cellulosic
      biomass.
AB  - The conventional biochemical platform featuring enzymatic hydrolysis involves
      five key steps: pretreatment, cellulase production, enzymatic hydrolysis,
      fermentation, and product recovery. Sugars are produced as reactive intermediates
      for subsequent fermentation to fuels and chemicals. Herein, an alternative
      biochemical route is proposed. Pretreatment, enzymatic hydrolysis and cellulase
      production is consolidated into one single step, referred to as consolidated
      aerobic processing, and sugar aldonates are produced as the reactive
      intermediates for biofuels production by fermentation. In this study, we
      demonstrate the viability of consolidation of the enzymatic hydrolysis and
      cellulase production steps in the new route using Neurospora crassa as the model
      microorganism and the conversion of cellulose to ethanol as the model system. We
      intended to prove the two hypotheses: 1) cellulose can be directed to produce
      cellobionate by reducing beta-glucosidase production and by enhancing cellobiose
      dehydrogenase production; and 2) both of the two hydrolysis products of
      cellobionate--glucose and gluconate--can be used as carbon sources for ethanol
      and other chemical production. Our results showed that knocking out multiple
      copies of beta-glucosidase genes led to cellobionate production from cellulose,
      without jeopardizing the cellulose hydrolysis rate. Simulating cellobiose
      dehydrogenase over-expression by addition of exogenous cellobiose dehydrogenase
      led to more cellobionate production. Both of the two hydrolysis products of
      cellobionate: glucose and gluconate can be used by Escherichia coli KO 11 for
      efficient ethanol production. They were utilized simultaneously in glucose and
      gluconate co-fermentation. Gluconate was used even faster than glucose. The
      results support the viability of the two hypotheses that lay the foundation for
      the proposed new route.

PMID- 22384059
TI  - Promotion of intestinal peristalsis by Bifidobacterium spp. capable of
      hydrolysing sennosides in mice.
AB  - BACKGROUND: While there are a variety of identifiable causes of constipation,
      even idiopathic constipation has different possible mechanisms. Sennosides, the
      main laxative constituents of Daio, an ancient Kampo medicine, are prodrugs that
      are converted to an active principle, rheinanthrone, by intestinal microbiota. In
      this study, we aimed to determine the sennoside hydrolysis ability of lactic acid
      bacterial strains and bifidobacteria in the intestine and to investigate their
      effect on intestinal peristalsis in mice. METHODOLOGY/PRINCIPAL FINDINGS: A total
      of 88 lactic acid bacterial strains and 47 bifidobacterial strains were evaluated
      for their ability to hydrolyze sennosides. Our results revealed that 4 strains,
      all belonging to the genus Bifidobacterium, had strong sennoside hydrolysis
      ability, exhibiting a decrease of >70% of sennoside content. By thin-layer
      chromatography analysis, rheinanthrone was detected in the medium cultured with
      B. pseudocatenulatum LKM10070 and B. animalis subsp. lactis LKM512. The fecal
      sennoside contents significantly (P<0.001) decreased upon oral administration of
      these strains as compared with the control. Intestinal peristalsis activity was
      measured by the moved distance of the charcoal powder administered orally. The
      distance travelled by the charcoal powder in LKM512-treated mice was
      significantly longer than that of control (P<0.05). Intestinal microbiota were
      analysed by real-time PCR and terminal-restriction fragment length polymorphism.
      The diversity of the intestinal microbiota was reduced by kanamycin treatment and
      the diversity was not recovered by LKM512 treatment. CONCLUSION/SIGNIFICANCE: We
      demonstrated that intestinal peristalsis was promoted by rheinanthrone produced
      by hydrolysis of sennoside by strain LKM512 and LKM10070.

PMID- 22384060
TI  - Are cuckoos maximizing egg mimicry by selecting host individuals with better
      matching egg phenotypes?
AB  - BACKGROUND: Avian brood parasites and their hosts are involved in complex offence
      defense coevolutionary arms races. The most common pair of reciprocal adaptations
      in these systems is egg discrimination by hosts and egg mimicry by parasites. As
      mimicry improves, more advanced host adaptations evolve such as decreased intra-
      and increased interclutch variation in egg appearance to facilitate detection of
      parasitic eggs. As interclutch variation increases, parasites able to choose
      hosts matching best their own egg phenotype should be selected, but this requires
      that parasites know their own egg phenotype and select host nests
      correspondingly. METHODOLOGY/PRINCIPAL FINDINGS: We compared egg mimicry of
      common cuckoo Cuculus canorus eggs in naturally parasitized marsh warbler
      Acrocephalus palustris nests and their nearest unparasitized conspecific
      neighbors having similar laying dates and nest-site characteristics. Modeling of
      avian vision and image analyses revealed no evidence that cuckoos parasitize
      nests where their eggs better match the host eggs. Cuckoo eggs were as good
      mimics, in terms of background and spot color, background luminance, spotting
      pattern and egg size, of host eggs in the nests actually exploited as those in
      the neighboring unparasitized nests. CONCLUSIONS/SIGNIFICANCE: We reviewed the
      evidence for brood parasites selecting better-matching host egg phenotypes from
      several relevant studies and argue that such selection probably cannot exist in
      host-parasite systems where host interclutch variation is continuous and overall
      low or moderate. To date there is also no evidence that parasites prefer certain
      egg phenotypes in systems where it should be most advantageous, i.e., when both
      hosts and parasites lay polymorphic eggs. Hence, the existence of an ability to
      select host nests to maximize mimicry by brood parasites appears unlikely, but
      this possibility should be further explored in cuckoo-host systems where the host
      has evolved discrete egg phenotypes.

PMID- 22384061
TI  - Comparison of methods to correct survival estimates and survival regression
      analysis on a large HIV African cohort.
AB  - OBJECTIVE: The evaluation of HIV treatment programs is generally based on an
      estimation of survival among patients receiving antiretroviral treatment (ART).
      In large HIV programs, loss to follow-up (LFU) rates remain high despite active
      patient tracing, which is likely to bias survival estimates and survival
      regression analyses. METHODS: We compared uncorrected survival estimates derived
      from routine program data with estimates obtained by applying six correction
      methods that use updated outcome data by a field survey targeting LFU patients in
      a rural HIV program in Malawi. These methods were based on double-sampling and
      differed according to the weights given to survival estimates in LFU and non-LFU
      subpopulations. We then proposed a correction of the survival regression
      analysis. RESULTS: Among 6,727 HIV-infected adults receiving ART, 9% were LFU
      after one year. The uncorrected survival estimates from routine data were 91% in
      women and 84% in men. According to increasing sophistication of the correction
      methods, the corrected survival estimates ranged from 89% to 85% in women and 82%
      to 77% in men. The estimates derived from uncorrected regression analyses were
      highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76
      1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma
      diagnosis (2.11; 1.61-2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40;
      1.17-1.66 vs. 1.29 to 1.34). CONCLUSIONS: In HIV programs with high LFU rates,
      the use of correction methods based on non-exhaustive double-sampling data are
      necessary to minimise the bias in survival estimates and survival regressions.

PMID- 22384063
TI  - A data-driven predictive approach for drug delivery using machine learning
      techniques.
AB  - In drug delivery, there is often a trade-off between effective killing of the
      pathogen, and harmful side effects associated with the treatment. Due to the
      difficulty in testing every dosing scenario experimentally, a computational
      approach will be helpful to assist with the prediction of effective drug delivery
      methods. In this paper, we have developed a data-driven predictive system, using
      machine learning techniques, to determine, in silico, the effectiveness of drug
      dosing. The system framework is scalable, autonomous, robust, and has the ability
      to predict the effectiveness of the current drug treatment and the subsequent
      drug-pathogen dynamics. The system consists of a dynamic model incorporating both
      the drug concentration and pathogen population into distinct states. These states
      are then analyzed using a temporal model to describe the drug-cell interactions
      over time. The dynamic drug-cell interactions are learned in an adaptive fashion
      and used to make sequential predictions on the effectiveness of the dosing
      strategy. Incorporated into the system is the ability to adjust the sensitivity
      and specificity of the learned models based on a threshold level determined by
      the operator for the specific application. As a proof-of-concept, the system was
      validated experimentally using the pathogen Giardia lamblia and the drug
      metronidazole in vitro.

PMID- 22384062
TI  - Non-small cell lung carcinoma cell motility, rac activation and metastatic
      dissemination are mediated by protein kinase C epsilon.
AB  - BACKGROUND: Protein kinase C (PKC) epsilon, a key signaling transducer implicated
      in mitogenesis, survival, and cancer progression, is overexpressed in human
      primary non-small cell lung cancer (NSCLC). The role of PKCepsilon in lung cancer
      metastasis has not yet been established. PRINCIPAL FINDINGS: Here we show that
      RNAi-mediated knockdown of PKCepsilon in H358, H1299, H322, and A549 NSCLC
      impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate
      13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCepsilon depletion
      markedly impaired the ability of NSCLC cells to form membrane ruffles and
      migrate. Similar results were observed by pharmacological inhibition of
      PKCepsilon with epsilonV1-2, a specific PKCepsilon inhibitor. PKCepsilon was also
      required for invasiveness of NSCLC cells and modulated the secretion of
      extracellular matrix proteases and protease inhibitors. Finally, we found that
      PKCepsilon-depleted NSCLC cells fail to disseminate to lungs in a mouse model of
      metastasis. CONCLUSIONS: Our results implicate PKCepsilon as a key mediator of
      Rac signaling and motility of lung cancer cells, highlighting its potential as a
      therapeutic target.

PMID- 22384064
TI  - Reconstruction of hematopoietic inductive microenvironment after transplantation
      of VCAM-1-modified human umbilical cord blood stromal cells.
AB  - The hematopoietic inductive microenvironment (HIM) is where hematopoietic
      stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key
      components of the HIM. In our previous study, we had successfully cultured and
      isolated human cord blood-derived stromal cells (HUCBSCs) and demonstrated that
      they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF.
      However, it is still controversial whether HUCBSCs can be used for reconstruction
      of HIM. In this study, we first established a co-culture system of HUCBSCs and
      cord blood CD34(+) cells and then determined that using HUCBSCs as the adherent
      layer had significantly more newly formed colonies of each hematopoietic lineage
      than the control group, indicating that HUCBSCs had the ability to promote the
      proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the
      number of colonies was significantly higher in vascular cell adhesion molecule-1
      (VCAM-1)-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting
      the proliferation of hematopoietic stem cells/progenitor cells was further
      enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into
      a radiation-damaged animal model, in which the recovery of hematopoiesis was
      observed. The results demonstrate that the transplanted HUCBSCs were "homed in"
      to bone marrow and played roles in promoting the recovery of irradiation-induced
      hematopoietic damage and repairing HIM. Compared with the control group, the
      HUCBSC group had significantly superior effectiveness in terms of the recovery
      time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such
      differences were even more significant in VCAM-1-modified HUCBSCs group. We
      suggest that HUCBSCs are able to restore the functions of HIM and promote the
      recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important
      role in supporting the repair of HIM damage.

PMID- 22384065
TI  - Structural diversity in bacterial ribosomes: mycobacterial 70S ribosome structure
      reveals novel features.
AB  - Here we present analysis of a 3D cryo-EM map of the 70S ribosome from
      Mycobacterium smegmatis, a saprophytic cousin of the etiological agent of
      tuberculosis in humans, Mycobacterium tuberculosis. In comparison with the 3D
      structures of other prokaryotic ribosomes, the density map of the M. smegmatis
      70S ribosome reveals unique structural features and their relative orientations
      in the ribosome. Dramatic changes in the periphery due to additional rRNA
      segments and extra domains of some of the peripheral ribosomal proteins like S3,
      S5, S16, L17, L25, are evident. One of the most notable features appears in the
      large subunit near L1 stalk as a long helical structure next to helix 54 of the
      23S rRNA. The sharp upper end of this structure is located in the vicinity of the
      mRNA exit channel. Although the M. smegmatis 70S ribosome possesses conserved
      core structure of bacterial ribosome, the new structural features, unveiled in
      this study, demonstrates diversity in the 3D architecture of bacterial ribosomes.
      We postulate that the prominent helical structure related to the 23S rRNA
      actively participates in the mechanisms of translation in mycobacteria.

PMID- 22384066
TI  - Age as a determinant for dissemination of seasonal and pandemic influenza: an
      open cohort study of influenza outbreaks in Ostergotland County, Sweden.
AB  - An understanding of the occurrence and comparative timing of influenza infections
      in different age groups is important for developing community response and
      disease control measures. This study uses data from a Scandinavian county
      (population 427.000) to investigate whether age was a determinant for being
      diagnosed with influenza 2005-2010 and to examine if age was associated with case
      timing during outbreaks. Aggregated demographic data were collected from
      Statistics Sweden, while influenza case data were collected from a county-wide
      electronic health record system. A logistic regression analysis was used to
      explore whether case risk was associated with age and outbreak. An analysis of
      variance was used to explore whether day for diagnosis was also associated to age
      and outbreak. The clinical case data were validated against case data from
      microbiological laboratories during one control year. The proportion of cases
      from the age groups 10-19 (p<0.001) and 20-29 years old (p<0.01) were found to be
      larger during the A pH1N1 outbreak in 2009 than during the seasonal outbreaks. An
      interaction between age and outbreak was observed (p<0.001) indicating a
      difference in age effects between circulating virus types; this interaction
      persisted for seasonal outbreaks only (p<0.001). The outbreaks also differed
      regarding when the age groups received their diagnosis (p<0.001). A post-hoc
      analysis showed a tendency for the young age groups, in particular the group 10
      19 year olds, led outbreaks with influenza type A H1 circulating, while A H3N2
      outbreaks displayed little variations in timing. The validation analysis showed a
      strong correlation (r = 0.625;p<0.001) between the recorded numbers of clinically
      and microbiologically defined influenza cases. Our findings demonstrate the
      complexity of age effects underlying the emergence of local influenza outbreaks.
      Disentangling these effects on the causal pathways will require an integrated
      information infrastructure for data collection and repeated studies of well
      defined communities.

PMID- 22384067
TI  - Transcriptome-wide survey of mouse CNS-derived cells reveals monoallelic
      expression within novel gene families.
AB  - Monoallelic expression is an integral component of regulation of a number of
      essential genes and gene families. To probe for allele-specific expression in
      cells of CNS origin, we used next-generation sequencing (RNA-seq) to analyze four
      clonal neural stem cell (NSC) lines derived from Mus musculus C57BL/6 (B6)*Mus
      musculus molossinus (JF1) adult female mice. We established a JF1 cSNP library,
      then ascertained transcriptome-wide expression from B6 vs. JF1 alleles in the NSC
      lines. Validating the assay, we found that 262 of 268 X-linked genes evaluable in
      at least one cell line showed monoallelic expression (at least 85% expression of
      the predominant allele, p-value<0.05). For autosomal genes 170 of 7,198 genes
      (2.4% of the total) showed monoallelic expression in at least 2 evaluable cell
      lines. The group included eight known imprinted genes with the expected pattern
      of allele-specific expression. Among the other autosomal genes with monoallelic
      expression were five members of the glutathione transferase gene superfamily,
      which processes xenobiotic compounds as well as carcinogens and cancer
      therapeutic agents. Monoallelic expression within this superfamily thus may play
      a functional role in the response to diverse and potentially lethal exogenous
      factors, as is the case for the immunoglobulin and olfactory receptor
      superfamilies. Other genes and gene families showing monoallelic expression
      include the annexin gene family and the Thy1 gene, both linked to inflammation
      and cancer, as well as genes linked to alcohol dependence (Gabrg1) and epilepsy
      (Kcnma1). The annotated set of genes will provide a resource for investigation of
      mechanisms underlying certain cases of these and other major disorders.

PMID- 22384068
TI  - The extended cleavage specificity of human thrombin.
AB  - Thrombin is one of the most extensively studied of all proteases. Its central
      role in the coagulation cascade as well as several other areas has been
      thoroughly documented. Despite this, its consensus cleavage site has never been
      determined in detail. Here we have determined its extended substrate recognition
      profile using phage-display technology. The consensus recognition sequence was
      identified as, P2-Pro, P1-Arg, P1'-Ser/Ala/Gly/Thr, P2'-not acidic and P3'-Arg.
      Our analysis also identifies an important role for a P3'-arginine in thrombin
      substrates lacking a P2-proline. In order to study kinetics of this cooperative
      or additive effect we developed a system for insertion of various pre-selected
      cleavable sequences in a linker region between two thioredoxin molecules. Using
      this system we show that mutations of P2-Pro and P3'-Arg lead to an approximate
      20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating
      both Pro and Arg results in a drop in cleavage of 200-400 times, which highlights
      the importance of these two positions for maximal substrate cleavage.
      Interestingly, no natural substrates display the obtained consensus sequence but
      represent sequences that show only 1-30% of the optimal cleavage rate for
      thrombin. This clearly indicates that maximal cleavage, excluding the help of
      exosite interactions, is not always desired, which may instead cause problems
      with dysregulated coagulation. It is likely exosite cooperativity has a central
      role in determining the specificity and rate of cleavage of many of these in vivo
      substrates. Major effects on cleavage efficiency were also observed for residues
      as far away as 4 amino acids from the cleavage site. Insertion of an aspartic
      acid in position P4 resulted in a drop in cleavage by a factor of almost 20
      times.

PMID- 22384069
TI  - Time in a bottle: the evolutionary fate of species discrimination in sibling
      Drosophila species.
AB  - Disadvantageous hybridization favors the evolution of prezygotic isolating
      behaviors, generating a geographic pattern of interspecific mate discrimination
      where members of different species drawn from sympatric populations exhibit
      stronger preference for members of their own species than do individuals drawn
      from allopatric populations. Geographic shifts in species' boundaries can relax
      local selection against hybridization; under such scenarios the fate of enhanced
      species preference is unknown. Lineages established from populations in the
      region of sympatry that have been maintained as single-species laboratory
      cultures represent cases where allopatry has been produced experimentally. Using
      such cultures dating from the 1950s, we assess how Drosophila pseudoobscura and
      D. persimilis mate preferences respond to relaxed natural selection against
      hybridization. We found that the propensity to hybridize generally declines with
      increasing time in experimental allopatry, suggesting that maintaining enhanced
      preference for conspecifics may be costly. However, our data also suggest a
      strong role for drift in determining mating preferences once secondary allopatry
      has been established. Finally, we discuss the interplay between populations in
      establishing the presence or absence of patterns consistent with reinforcement.

PMID- 22384070
TI  - AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: a gene
      association study.
AB  - Amateur choral singing is a common pastime and worthy of study, possibly
      conferring benefits to health and social behaviour. Participants might be
      expected to possess musical ability and share some behavioural characteristics.
      Polymorphisms in genes concerned with serotonergic neurotransmission are
      associated with both behaviour and musical aptitude. Those investigated
      previously include the variable number tandem repeats RS1, RS3 and AVR in the
      AVPR1A (arginine vasopressin receptor 1a) gene and STin2 in the SLC6A4 (solute
      carrier family 6 [neurotransmitter transporter, serotonin], member 4) gene, as
      well as the SLC6A4 promoter region polymorphism, 5-HTTLPR. We conducted a genetic
      association study on 523 participants to establish whether alleles at these
      polymorphisms occur more commonly in choral singers than in those not regularly
      participating in organised musical activity (non-musicians). We also analysed
      tagging single nucleotide polymorphisms (SNPs) for AVPR1A and SLC6A4 to determine
      whether other variants in these genes were associated with singer/non-musician
      status. At the STin2 polymorphism, overall association with singer/non-musician
      status was evident at P = 0.006. The 9-repeat (P = 0.04) and 12-repeat (P = 0.04)
      alleles were more common in singers and the 10-repeat allele less so (P = 0.009).
      Odds ratios were 0.73 (95% CI 0.57-0.94) for the 10-repeat allele and 2.47 (95%
      CI 0.88-6.94) for the rarer 9-repeat allele. No overall association was detected
      at P<0.05 between any other polymorphism and singer/non-musician status. Our null
      findings with respect to RS3, RS1 and AVR, polymorphisms associated with musical
      ability by other authors, suggest that choir membership may depend partly on
      factors other than musical ability. In a related musical project involving one
      participating choir, a new 40-part unaccompanied choral work, "Allele", was
      composed and broadcast on national radio. In the piece, each singer's part
      incorporated their personal RS3 genotype.

PMID- 22384071
TI  - Artifacts in magnetic resonance imaging and computed tomography caused by dental
      materials.
AB  - BACKGROUND: Artifacts caused by dental restorations, such as dental crowns,
      dental fillings and orthodontic appliances, are a common problem in MRI and CT
      scans of the head and neck. The aim of this in-vitro study was to identify and
      evaluate the artifacts produced by different dental restoration materials in CT
      and MRI images. METHODS: Test samples of 44 materials (Metal and Non-Metal)
      commonly used in dental restorations were fabricated and embedded with reference
      specimens in gelatin moulds. MRI imaging of 1.5T and CT scan were performed on
      the samples and evaluated in two dimensions. Artifact size and distortions were
      measured using a digital image analysis software. RESULTS: In MRI, 13 out of 44
      materials produced artifacts, while in CT 41 out of 44 materials showed
      artifacts. Artifacts produced in both MRI and CT images were categorized
      according to the size of the artifact. SIGNIFICANCE: Metal based restoration
      materials had strong influence on CT and less artifacts in MRI images. Rare earth
      elements such as Ytterbium trifluoride found in composites caused artifacts in
      both MRI and CT. Recognizing these findings would help dental materials
      manufacturers and developers to produce materials which can cause less artifacts
      in MRI and CT images.

PMID- 22384072
TI  - Catching a ball at the right time and place: individual factors matter.
AB  - Intercepting a moving object requires accurate spatio-temporal control. Several
      studies have investigated how the CNS copes with such a challenging task,
      focusing on the nature of the information used to extract target motion
      parameters and on the identification of general control strategies. In the
      present study we provide evidence that the right time and place of the collision
      is not univocally specified by the CNS for a given target motion; instead,
      different but equally successful solutions can be adopted by different subjects
      when task constraints are loose. We characterized arm kinematics of fourteen
      subjects and performed a detailed analysis on a subset of six subjects who showed
      comparable success rates when asked to catch a flying ball in three dimensional
      space. Balls were projected by an actuated launching apparatus in order to obtain
      different arrival flight time and height conditions. Inter-individual variability
      was observed in several kinematic parameters, such as wrist trajectory, wrist
      velocity profile, timing and spatial distribution of the impact point, upper limb
      posture, trunk motion, and submovement decomposition. Individual idiosyncratic
      behaviors were consistent across different ball flight time conditions and across
      two experimental sessions carried out at one year distance. These results
      highlight the importance of a systematic characterization of individual factors
      in the study of interceptive tasks.

PMID- 22384073
TI  - The association of Antarctic krill Euphausia superba with the under-ice habitat.
AB  - The association of Antarctic krill Euphausia superba with the under-ice habitat
      was investigated in the Lazarev Sea (Southern Ocean) during austral summer,
      autumn and winter. Data were obtained using novel Surface and Under Ice Trawls
      (SUIT), which sampled the 0-2 m surface layer both under sea ice and in open
      water. Average surface layer densities ranged between 0.8 individuals m(-2) in
      summer and autumn, and 2.7 individuals m(-2) in winter. In summer, under-ice
      densities of Antarctic krill were significantly higher than in open waters. In
      autumn, the opposite pattern was observed. Under winter sea ice, densities were
      often low, but repeatedly far exceeded summer and autumn maxima. Statistical
      models showed that during summer high densities of Antarctic krill in the 0-2 m
      layer were associated with high ice coverage and shallow mixed layer depths,
      among other factors. In autumn and winter, density was related to hydrographical
      parameters. Average under-ice densities from the 0-2 m layer were higher than
      corresponding values from the 0-200 m layer collected with Rectangular Midwater
      Trawls (RMT) in summer. In winter, under-ice densities far surpassed maximum 0
      200 m densities on several occasions. This indicates that the importance of the
      ice-water interface layer may be under-estimated by the pelagic nets and sonars
      commonly used to estimate the population size of Antarctic krill for management
      purposes, due to their limited ability to sample this habitat. Our results
      provide evidence for an almost year-round association of Antarctic krill with the
      under-ice habitat, hundreds of kilometres into the ice-covered area of the
      Lazarev Sea. Local concentrations of postlarval Antarctic krill under winter sea
      ice suggest that sea ice biota are important for their winter survival. These
      findings emphasise the susceptibility of an ecological key species to changing
      sea ice habitats, suggesting potential ramifications on Antarctic ecosystems
      induced by climate change.

PMID- 22384074
TI  - Endoplasmic reticulum stress-sensing mechanism is activated in Entamoeba
      histolytica upon treatment with nitric oxide.
AB  - The Endoplasmic Reticulum stores calcium and is a site of protein synthesis and
      modification. Changes in ER homeostasis lead to stress responses with an
      activation of the unfolded protein response (UPR). The Entamoeba histolytica
      endomembrane system is simple compared to those of higher eukaryotes, as a
      canonical ER is not observed. During amoebiasis, an infection of the human
      intestine and liver by E. histolytica, nitric oxide (NO) triggers an apoptotic
      like event preceded by an impairment of energy production and a loss of important
      parasite pathogenic features. We address the question of how this ancient
      eukaryote responds to stress induced by immune components (i.e. NO) and whether
      stress leads to ER changes and subsequently to an UPR. Gene expression analysis
      suggested that NO triggers stress responses marked by (i) dramatic up-regulation
      of hsp genes although a bona fide UPR is absent; (ii) induction of DNA repair and
      redox gene expression and iii) up-regulation of glycolysis-related gene
      expression. Enzymology approaches demonstrate that NO directly inhibits
      glycolysis and enhance cysteine synthase activity. Using live imaging and
      confocal microscopy we found that NO dramatically provokes extensive ER
      fragmentation. ER fission in E. histolytica appears as a protective response
      against stress, as it has been recently proposed for neuron self-defense during
      neurologic disorders. Chronic ER stress is also involved in metabolic diseases
      including diabetes, where NO production reduces ER calcium levels and activates
      cell death. Our data highlighted unique cellular responses of interest to
      understand the mechanisms of parasite death during amoebiasis.

PMID- 22384075
TI  - Prevalence of metabolic syndrome in Iranian professional drivers: results from a
      population based study of 12,138 men.
AB  - BACKGROUND: It is evident that professional driving is associated with
      substantial changes in lifestyle habits. Professional drivers are prone to
      metabolic syndrome (MetS) and its complications because their working environment
      is characterized by numerous stress factors such as lack of physical activity due
      to working in a fixed position, disruption in diet, and irregular sleep habits.
      The aim of the present study was to estimate the prevalence of MetS among long
      distance drivers residing in West Azerbaijan province in Iran. MATERIALS: To
      assess the prevalence of metabolic syndrome among professional long distance
      drivers, 12138 participants were enrolled in this cross sectional study. The MetS
      was defined using International Diabetes Federation criteria. RESULTS: Among
      12138 participants, 3697 subjects found to be MetS. The crude and age-adjusted
      rates of MetS were 30.5% and 32.4% respectively. Based on Body mass index (BMI),
      5027 subjects (41.4%) were overweight (BMI >= 25.01-30 kg/m2), and 2592 (21.3%)
      were obese (BMI >= 30.01 kg/m2). The presence of central obesity was more common
      than other components. The associations of MetS with BMI, pack-year smoking, age,
      weekly driving duration and driving experiences were significant in the logistic
      regression. By increasing BMI, pack-year smoking, age, weekly driving duration
      and driving experiences, odds ratio of MetS was increased. CONCLUSION: The study
      suggests that MetS has become a noteworthy health problem among Iranian long
      distance drivers. This might be due to the following facts: sitting in a fixed
      position for long hours while working, cigarette smoking, job stress, unhealthy
      diet and lack of physical activity. Educational programs should be established
      for promoting healthy lifestyle and also for early detection and appropriate
      interventions.

PMID- 22384076
TI  - A 24-hour temporal profile of in vivo brain and heart pet imaging reveals a
      nocturnal peak in brain 18F-fluorodeoxyglucose uptake.
AB  - Using positron emission tomography, we measured in vivo uptake of (18)F
      fluorodeoxyglucose (FDG) in the brain and heart of C57Bl/6 mice at intervals
      across a 24-hour light-dark cycle. Our data describe a significant, high
      amplitude rhythm in FDG uptake throughout the whole brain, peaking at the mid
      dark phase of the light-dark cycle, which is the active phase for nocturnal mice.
      Under these conditions, heart FDG uptake did not vary with time of day, but did
      show biological variation throughout the 24-hour period for measurements within
      the same mice. FDG uptake was scanned at different times of day within an
      individual mouse, and also compared to different times of day between
      individuals, showing both biological and technical reproducibility of the 24-hour
      pattern in FDG uptake. Regional analysis of brain FDG uptake revealed especially
      high amplitude rhythms in the olfactory bulb and cortex, while low amplitude
      rhythms were observed in the amygdala, brain stem and hypothalamus. Low amplitude
      24-hour rhythms in regional FDG uptake may be due to multiple rhythms with
      different phases in a single brain structure, quenching some of the amplitude.
      Our data show that the whole brain exhibits significant, high amplitude daily
      variation in glucose uptake in living mice. Reports applying the 2-deoxy-D[(14)C]
      glucose method for the quantitative determination of the rates of local cerebral
      glucose utilization indicate only a small number of brain regions exhibiting a
      day versus night variation in glucose utilization. In contrast, our data show 24
      hour patterns in glucose uptake in most of the brain regions examined, including
      several regions that do not show a difference in glucose utilization. Our data
      also emphasizes a methodological requirement of controlling for the time of day
      of scanning FDG uptake in the brain in both clinical and pre-clinical settings,
      and suggests waveform normalization of FDG measurements at different times of the
      day.

PMID- 22384077
TI  - Novel insights into the downstream pathways and targets controlled by
      transcription factors CREM in the testis.
AB  - The essential role of the Crem gene in normal sperm development is widely
      accepted and is confirmed by azoospermia in male mice lacking the Crem gene. The
      exact number of genes affected by Crem absence is not known, however a large
      difference has been observed recently between the estimated number of
      differentially expressed genes found in Crem knock-out (KO) mice compared to the
      number of gene loci bound by CREM. We therefore re-examined global gene
      expression in male mice lacking the Crem gene using whole genome transcriptome
      analysis with Affymetrix microarrays and compared the lists of differentially
      expressed genes from Crem-/- mice to a dataset of genes where binding of CREM was
      determined by Chip-seq. We determined the global effect of CREM on
      spermatogenesis as well as distinguished between primary and secondary effects of
      the CREM absence. We demonstrated that the absence of Crem deregulates over 4700
      genes in KO testis. Among them are 101 genes associated with spermatogenesis 41
      of which are bound by CREM and are deregulated in Crem KO testis. Absence of
      several of these genes in mouse models has proven their importance for normal
      spermatogenesis and male fertility. Our study showed that the absence of Crem
      plays a more important role on different aspects of spermatogenesis as estimated
      previously, with its impact ranging from apoptosis induction to deregulation of
      major circadian clock genes, steroidogenesis and the cell-cell junction dynamics.
      Several new genes important for normal spermatogenesis and fertility are down
      regulated in KO testis and are therefore possible novel targets of CREM.

PMID- 22384078
TI  - (+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression
      efficiently ameliorates glucose homeostasis in insulin-resistant mice.
AB  - Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to
      insulin, and impaired translocation or decreased expression of GLUT4 is believed
      to be one of the major pathological features of type 2 diabetes mellitus (T2DM).
      Therefore, induction of GLUT4 translocation or/and expression is a promising
      strategy for anti-T2DM drug discovery. Here we report that the natural product
      (+)-Rutamarin (Rut) functions as an efficient dual inducer on both insulin
      induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit
      efficiently enhanced insulin-induced glucose uptake, while diet-induced obese
      (DIO) mice based assays further confirm the Rut-induced improvement of glucose
      homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut
      acting targets indicates that as a specific protein tyrosine phosphatase 1B
      (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and
      largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB
      pathway, while as an agonist of retinoid X receptor alpha (RXRalpha), Rut
      potently increases GLUT4 expression. Furthermore, by using molecular modeling and
      crystallographic approaches, the possible binding modes of Rut to these two
      targets have been also determined at atomic levels. All our results have thus
      highlighted the potential of Rut as both a valuable lead compound for anti-T2DM
      drug discovery and a promising chemical probe for GLUT4 associated pathways
      exploration.

PMID- 22384079
TI  - Physiological stress and refuge behavior by African elephants.
AB  - Physiological stress responses allow individuals to adapt to changes in their
      status or surroundings, but chronic exposure to stressors could have detrimental
      effects. Increased stress hormone secretion leads to short-term escape behavior;
      however, no studies have assessed the potential of longer-term escape behavior,
      when individuals are in a chronic physiological state. Such refuge behavior is
      likely to take two forms, where an individual or population restricts its space
      use patterns spatially (spatial refuge hypothesis), or alters its use of space
      temporally (temporal refuge hypothesis). We tested the spatial and temporal
      refuge hypotheses by comparing space use patterns among three African elephant
      populations maintaining different fecal glucocorticoid metabolite (FGM)
      concentrations. In support of the spatial refuge hypothesis, the elephant
      population that maintained elevated FGM concentrations (iSimangaliso) used 20%
      less of its reserve than did an elephant population with lower FGM concentrations
      (Pilanesberg) in a reserve of similar size, and 43% less than elephants in the
      smaller Phinda reserve. We found mixed support for the temporal refuge
      hypothesis; home range sizes in the iSimangaliso population did not differ by day
      compared to nighttime, but elephants used areas within their home ranges
      differently between day and night. Elephants in all three reserves generally
      selected forest and woodland habitats over grasslands, but elephants in
      iSimangaliso selected exotic forest plantations over native habitat types. Our
      findings suggest that chronic stress is associated with restricted space use and
      altered habitat preferences that resemble a facultative refuge behavioral
      response. Elephants can maintain elevated FGM levels for >= 6 years following
      translocation, during which they exhibit refuge behavior that is likely a result
      of human disturbance and habitat conditions. Wildlife managers planning to
      translocate animals, or to initiate other management activities that could result
      in chronic stress responses, should consider the potential for, and consequences
      of, refuge behavior.

PMID- 22384080
TI  - Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of
      acute patients and individuals recovered from hepatitis E infection.
AB  - BACKGROUND: Hepatitis E is a major public health problem in the developing
      countries. Pathogenesis of hepatitis E virus (HEV) infection is poorly
      understood. METHODS: This case-control study included 124 Hepatitis E patients
      (46 acute and 78 recovered), 9 with prior exposure to HEV and 71 anti-HEV
      negative healthy controls. HEV induced CTL response by Elispot,
      cytokines/chemokines quantitation by Milliplex assay and peripheral CD4+ & CD8+ T
      cell frequencies by flow cytometry were assessed. RESULTS: Among the patient
      categories, HEV specific IFN-gamma responses as recorded by Elispot were
      comparable. Comparisons of cytokines/chemokines revealed significantly high
      levels of IL-1alpha and sIL-2Ralpha during acute phase. Circulating peripheral
      CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable
      compared to controls, while among patient categories CD8+T cell subset was
      significantly higher in recovered individuals. CONCLUSIONS: Our findings suggest
      that IL-1alpha and sIL-2Ralpha play a role in the pathogenesis of acute Hepatitis
      E infection. Lack of robust HEV ORF2-specific CTL response in the peripheral
      blood of HEV infected patients during the acute and recovered phases of the
      disease may be associated with involvement of innate immune cells/localization of
      the immune events at the site of infection.

PMID- 22384081
TI  - Wnt5a is strongly expressed at the leading edge in non-melanoma skin cancer,
      forming active gradients, while canonical Wnt signalling is repressed.
AB  - Wnt5a is one of the so-called non-canonical Wnt ligands which do not act through
      beta-catenin. In normal development, Wnt5a is secreted and directs the migration
      of target cells along concentration gradients. The effect of Wnt5a on target
      cells is regulated by many factors, including the expression level of inhibitors
      and receptors. Dysregulated Wnt5a signalling facilitates invasion of multiple
      tumor types into adjacent tissue. However, the expression and distribution of
      Wnt5a in cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC),
      as well as the effect of Wnt5a on keratinocyte migration has not been studied in
      detail to date. We here report that Wnt5a is upregulated in SCC and BCC and
      localised to the leading edge of tumors, as well as tumor-associated fibroblasts.
      The Wnt5a-triggered bundling of its receptor Fzd3 provides evidence of Wnt5a
      concentration gradients projecting into the tumor. In vitro migration assays show
      that Wnt5a concentration gradients determine its effect on keratinoctye
      migration: While chemotactic migration is inhibited by Wnt5a present in
      homogenous concentrations, it is enhanced in the presence of a Wnt5a gradient.
      Expression profiling of the Wnt pathway shows that the upregulation of Wnt5a in
      SCC is coupled to repression of canonical Wnt signalling. This is confirmed by
      immunohistochemistry showing lack of nuclear beta-catenin, as well as absent
      accumulation of Axin2. Since both types of Wnt signalling act mutually
      antogonistically at multiple levels, the concurrent repression of canonical Wnt
      signalling suggests hyper-active Wnt5a signal transduction. Significantly, this
      combination of gene dysregulation is not observed in the benign
      hyperproliferative inflammatory skin disease psoriasis. Collectively, our data
      strongly suggest that Wnt5a signalling contributes to tissue invasion by non
      melanoma skin cancer.

PMID- 22384082
TI  - Metatranscriptomics and pyrosequencing facilitate discovery of potential viral
      natural enemies of the invasive Caribbean crazy ant, Nylanderia pubens.
AB  - BACKGROUND: Nylanderia pubens (Forel) is an invasive ant species that in recent
      years has developed into a serious nuisance problem in the Caribbean and United
      States. A rapidly expanding range, explosive localized population growth, and
      control difficulties have elevated this ant to pest status. Professional
      entomologists and the pest control industry in the United States are urgently
      trying to understand its biology and develop effective control methods.
      Currently, no known biological-based control agents are available for use in
      controlling N. pubens. METHODOLOGY AND PRINCIPAL FINDINGS: Metagenomics and
      pyrosequencing techniques were employed to examine the transcriptome of field
      collected N. pubens colonies in an effort to identify virus infections with
      potential to serve as control agents against this pest ant. Pyrosequencing (454
      platform) of a non-normalized N. pubens expression library generated 1,306,177
      raw sequence reads comprising 450 Mbp. Assembly resulted in generation of 59,017
      non-redundant sequences, including 27,348 contigs and 31,669 singlets. BLAST
      analysis of these non-redundant sequences identified 51 of potential viral
      origin. Additional analyses winnowed this list of potential viruses to three that
      appear to replicate in N. pubens. CONCLUSIONS: Pyrosequencing the transcriptome
      of field-collected samples of N. pubens has identified at least three sequences
      that are likely of viral origin and, in which, N. pubens serves as host. In
      addition, the N. pubens transcriptome provides a genetic resource for the
      scientific community which is especially important at this early stage of
      developing a knowledgebase for this new pest.

PMID- 22384084
TI  - Comparative gene expression profiling of P. falciparum malaria parasites exposed
      to three different histone deacetylase inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors are being intensively pursued as potential
      new drugs for a range of diseases, including malaria. HDAC inhibitors are also
      important tools for the study of epigenetic mechanisms, transcriptional control,
      and other important cellular processes. In this study the effects of three
      structurally related antimalarial HDAC inhibitors on P. falciparum malaria
      parasite gene expression were compared. The three hydroxamate-based compounds,
      trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA; Vorinostat(r)) and a
      2-aminosuberic acid derivative (2-ASA-9), all caused profound transcriptional
      effects, with ~2-21% of genes having >2-fold altered expression following 2 h
      exposure to the compounds. Only two genes, alpha tubulin II and a hydrolase, were
      up-regulated by all three compounds after 2 h exposure in all biological
      replicates examined. The transcriptional changes observed after 2 h exposure to
      HDAC inhibitors were found to be largely transitory, with only 1-5% of genes
      being regulated after removing the compounds and culturing for a further 2 h.
      Despite some structural similarity, the three inhibitors caused quite diverse
      transcriptional effects, possibly reflecting subtle differences in mode of action
      or cellular distribution. This dataset represents an important contribution to
      our understanding of how HDAC inhibitors act on malaria parasites and identifies
      alpha tubulin II as a potential transcriptional marker of HDAC inhibition in
      malaria parasites that may be able to be exploited for future development of HDAC
      inhibitors as new antimalarial agents.

PMID- 22384083
TI  - Genetic abolishment of hepatocyte proliferation activates hepatic stem cells.
AB  - Quiescent hepatic stem cells (HSCs) can be activated when hepatocyte
      proliferation is compromised. Chemical injury rodent models have been widely used
      to study the localization, biomarkers, and signaling pathways in HSCs, but these
      models usually exhibit severe promiscuous toxicity and fail to distinguish
      damaged and non-damaged cells. Our goal is to establish new animal models to
      overcome these limitations, thereby providing new insights into HSC biology and
      application. We generated mutant mice with constitutive or inducible deletion of
      Damaged DNA Binding protein 1 (DDB1), an E3 ubiquitin ligase, in hepatocytes. We
      characterized the molecular mechanism underlying the compensatory activation and
      the properties of oval cells (OCs) by methods of mouse genetics, immuno-staining,
      cell transplantation and gene expression profiling. We show that deletion of DDB1
      abolishes self-renewal capacity of mouse hepatocytes in vivo, leading to
      compensatory activation and proliferation of DDB1-expressing OCs. Partially
      restoring proliferation of DDB1-deficient hepatocytes by ablation of p21, a
      substrate of DDB1 E3 ligase, alleviates OC proliferation. Purified OCs express
      both hepatocyte and cholangiocyte markers, form colonies in vitro, and
      differentiate to hepatocytes after transplantation. Importantly, the DDB1 mutant
      mice exhibit very minor liver damage, compared to a chemical injury model.
      Microarray analysis reveals several previously unrecognized markers, including
      Reelin, enriched in oval cells. Here we report a genetic model in which
      irreversible inhibition of hepatocyte duplication results in HSC-driven liver
      regeneration. The DDB1 mutant mice can be broadly applied to studies of HSC
      differentiation, HSC niche and HSCs as origin of liver cancer.

PMID- 22384085
TI  - Ccdc80-l1 Is involved in axon pathfinding of zebrafish motoneurons.
AB  - Axon pathfinding is a subfield of neural development by which neurons send out
      axons to reach the correct targets. In particular, motoneurons extend their axons
      toward skeletal muscles, leading to spontaneous motor activity. In this study, we
      identified the zebrafish Ccdc80 and Ccdc80-like1 (Ccdc80-l1) proteins in silico
      on the basis of their high aminoacidic sequence identity with the human CCDC80
      (Coiled-Coil Domain Containing 80). We focused on ccdc80-l1 gene that is
      expressed in nervous and non-nervous tissues, in particular in territories
      correlated with axonal migration, such as adaxial cells and muscle pioneers. Loss
      of ccdc80-l1 in zebrafish embryos induced motility issues, although somitogenesis
      and myogenesis were not impaired. Our results strongly suggest that ccdc80-l1 is
      involved in axon guidance of primary and secondary motoneurons populations, but
      not in their proper formation. ccdc80-l1 has a differential role as regards the
      development of ventral and dorsal motoneurons, and this is consistent with the
      asymmetric distribution of the transcript. The axonal migration defects observed
      in ccdc80-l1 loss-of-function embryos are similar to the phenotype of several
      mutants with altered Hedgehog activity. Indeed, we reported that ccdc80-l1
      expression is positively regulated by the Hedgehog pathway in adaxial cells and
      muscle pioneers. These findings strongly indicate ccdc80-l1 as a down-stream
      effector of the Hedgehog pathway.

PMID- 22384086
TI  - Fructose-bisphophate aldolase exhibits functional roles between carbon metabolism
      and the hrp system in rice pathogen Xanthomonas oryzae pv. oryzicola.
AB  - Fructose-bisphophate aldolase (FbaB), is an enzyme in glycolysis and
      gluconeogenesis in living organisms. The mutagenesis in a unique fbaB gene of
      Xanthomonas oryzae pv. oryzicola, the causal agent of rice bacterial leaf streak,
      led the pathogen not only unable to use pyruvate and malate for growth and
      delayed its growth when fructose was used as the sole carbon source, but also
      reduced extracellular polysaccharide (EPS) production and impaired bacterial
      virulence and growth in rice. Intriguingly, the fbaB promoter contains an
      imperfect PIP-box (plant-inducible promoter) (TTCGT-N(9)-TTCGT). The expression
      of fbaB was negatively regulated by a key hrp regulatory HrpG and HrpX cascade.
      Base substitution in the PIP-box altered the regulation of fbaB with the cascade.
      Furthermore, the expression of fbaB in X. oryzae pv. oryzicola RS105 strain was
      inducible in planta rather than in a nutrient-rich medium. Except other hrp-hrc
      hpa genes, the expression of hrpG and hrpX was repressed and the transcripts of
      hrcC, hrpE and hpa3 were enhanced when fbaB was deleted. The mutation in hrcC,
      hrpE or hpa3 reduced the ability of the pathogen to acquire pyruvate and malate.
      In addition, bacterial virulence and growth in planta and EPS production in
      RDeltafbaB mutant were completely restored to the wild-type level by the presence
      of fbaB in trans. This is the first report to demonstrate that carbohydrates,
      assimilated by X. oryzae pv. oryzicola, play critical roles in coordinating hrp
      gene expression through a yet unknown regulator.

PMID- 22384087
TI  - A phylogenetic analysis of the globins in fungi.
AB  - BACKGROUND: All globins belong to one of three families: the F (flavohemoglobin)
      and S (sensor) families that exhibit the canonical 3/3 alpha-helical fold, and
      the T (truncated 3/3 fold) globins characterized by a shortened 2/2 alpha-helical
      fold. All eukaryote 3/3 hemoglobins are related to the bacterial single domain F
      globins. It is known that Fungi contain flavohemoglobins and single domain S
      globins. Our aims are to provide a census of fungal globins and to examine their
      relationships to bacterial globins. RESULTS: Examination of 165 genomes revealed
      that globins are present in >90% of Ascomycota and ~60% of Basidiomycota genomes.
      The S globins occur in Blastocladiomycota and Chytridiomycota in addition to the
      phyla that have FHbs. Unexpectedly, group 1 T globins were found in one
      Blastocladiomycota and one Chytridiomycota genome. Phylogenetic analyses were
      carried out on the fungal globins, alone and aligned with representative
      bacterial globins. The Saccharomycetes and Sordariomycetes with two FHbs form two
      widely divergent clusters separated by the remaining fungal sequences. One of the
      Saccharomycete groups represents a new subfamily of FHbs, comprising a previously
      unknown N-terminal and a FHb missing the C-terminal moiety of its reductase
      domain. The two Saccharomycete groups also form two clusters in the presence of
      bacterial FHbs; the surrounding bacterial sequences are dominated by
      Proteobacteria and Bacilli (Firmicutes). The remaining fungal FHbs cluster with
      Proteobacteria and Actinobacteria. The Sgbs cluster separately from their
      bacterial counterparts, except for the intercalation of two Planctomycetes and a
      Proteobacterium between the Fungi incertae sedis and the Blastocladiomycota and
      Chytridiomycota. CONCLUSION: Our results are compatible with a model of globin
      evolution put forward earlier, which proposed that eukaryote F, S and T globins
      originated via horizontal gene transfer of their bacterial counterparts to the
      eukaryote ancestor, resulting from the endosymbiotic events responsible for the
      origin of mitochondria and chloroplasts.

PMID- 22384088
TI  - Evaluation of functional erythropoietin receptor status in skeletal muscle in
      vivo: acute and prolonged studies in healthy human subjects.
AB  - BACKGROUND: Erythropoietin receptors have been identified in human skeletal
      muscle tissue, but downstream signal transduction has not been investigated. We
      therefore studied in vivo effects of systemic erythropoietin exposure in human
      skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: The protocols involved 1) acute
      effects of a single bolus injection of erythropoietin followed by consecutive
      muscle biopsies for 1-10 hours, and 2) a separate study with prolonged
      administration for 16 days with biopsies obtained before and after. The presence
      of erythropoietin receptors in muscle tissue as well as activation of Epo
      signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting.
      Changes in muscle protein profiles after prolonged erythropoietin treatment were
      evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the
      erythropoietin receptor in skeletal muscle was confirmed, by the M20 but not the
      C20 antibody. However, no significant changes in phosphorylation of the Epo-R,
      STAT5, MAPK, Akt, Lyn, IKK, and p70S6K after erythropoietin administration were
      detected. The level of 8 protein spots were significantly altered after 16 days
      of rHuEpo treatment; one isoform of myosin light chain 3 and one of desmin/actin
      were decreased, while three isoforms of creatine kinase and two of glyceraldehyd
      3-phosphate dehydrogenase were increased. CONCLUSIONS/SIGNIFICANCE: Acute
      exposure to recombinant human erythropoietin is not associated by detectable
      activation of the Epo-R or downstream signalling targets in human skeletal muscle
      in the resting situation, whereas more prolonged exposure induces significant
      changes in the skeletal muscle proteome. The absence of functional Epo receptor
      activity in human skeletal muscle indicates that the long-term effects are
      indirect and probably related to an increased oxidative capacity in this tissue.

PMID- 22384089
TI  - Functional complexity of the axonal growth cone: a proteomic analysis.
AB  - The growth cone, the tip of the emerging neurite, plays a crucial role in
      establishing the wiring of the developing nervous system. We performed an
      extensive proteomic analysis of axonal growth cones isolated from the brains of
      fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at >= 99%
      confidence level. Using informatics, including functional annotation cluster and
      KEGG pathway analysis, we found great diversity of proteins involved in axonal
      pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate
      metabolism, as expected. We also found a large and complex array of proteins
      involved in translation, protein folding, posttranslational processing, and
      proteasome/ubiquitination-dependent degradation. Immunofluorescence studies
      performed on hippocampal neurons in culture confirmed the presence in the axonal
      growth cone of proteins representative of these processes. These analyses also
      provide evidence for rough endoplasmic reticulum and reveal a reticular structure
      equipped with Golgi-like functions in the axonal growth cone. Furthermore,
      Western blot revealed the growth cone enrichment, relative to fetal brain
      homogenate, of some of the proteins involved in protein synthesis, folding and
      catabolism. Our study provides a resource for further research and amplifies the
      relatively recently developed concept that the axonal growth cone is equipped
      with proteins capable of performing a highly diverse range of functions.

PMID- 22384090
TI  - Bmi1 is down-regulated in the aging brain and displays antioxidant and protective
      activities in neurons.
AB  - Aging increases the risk to develop several neurodegenerative diseases, although
      the underlying mechanisms are poorly understood. Inactivation of the Polycomb
      group gene Bmi1 in mice results in growth retardation, cerebellar degeneration,
      and development of a premature aging-like phenotype. This progeroid phenotype is
      characterized by formation of lens cataracts, apoptosis of cortical neurons, and
      increase of reactive oxygen species (ROS) concentrations, owing to p53-mediated
      repression of antioxidant response (AOR) genes. Herein we report that Bmi1
      expression progressively declines in the neurons of aging mouse and human brains.
      In old brains, p53 accumulates at the promoter of AOR genes, correlating with a
      repressed chromatin state, down-regulation of AOR genes, and increased oxidative
      damages to lipids and DNA. Comparative gene expression analysis further revealed
      that aging brains display an up-regulation of the senescence-associated genes IL
      6, p19(Arf) and p16(Ink4a), along with the pro-apoptotic gene Noxa, as seen in
      Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust
      protection against DNA damage-induced cell death or mitochondrial poisoning, and
      resulted in suppression of ROS through activation of AOR genes. These
      observations unveil that Bmi1 genetic deficiency recapitulates aspects of
      physiological brain aging and that Bmi1 over-expression is a potential
      therapeutic modality against neurodegeneration.

PMID- 22384091
TI  - Shear stress modulation of IL-1beta-induced E-selectin expression in human
      endothelial cells.
AB  - BACKGROUND: Endothelial cells (ECs) are continuously exposed to hemodynamic
      forces imparted by blood flow. While it is known that endothelial behavior can be
      influenced by cytokine activation or fluid shear, the combined effects of these
      two independent agonists have yet to be fully elucidated. METHODOLOGY: We
      investigated EC response to long-term inflammatory cues under physiologically
      relevant shear conditions via E-selectin expression where monolayers of human
      umbilical vein ECs were simultaneously exposed to laminar fluid shear and
      interleukin-1beta (shear-cytokine activation) in a parallel plate flow chamber.
      RESULTS AND CONCLUSION: Naive ECs exposed to shear-cytokine activation display
      significantly higher E-selectin expression for up to 24 hr relative to ECs
      activated in static (static-cytokine). Peak E-selectin expression occurred after
      8-12 hr of continuous shear-cytokine activation contrary to the commonly observed
      4-6 hr peak expression in ECs exposed to static-cytokine activation. Cells with
      some history of high shear conditioning exhibited either high or muted E-selectin
      expression depending on the durations of the shear pre-conditioning and the
      ensuing shear-cytokine activation. Overall, the presented data suggest that a
      high laminar shear enhances acute EC response to interleukin-1beta in naive or
      shear-conditioned ECs as may be found in the pathological setting of
      ischemia/reperfusion injury while conferring rapid E-selectin downregulation to
      protect against chronic inflammation.

PMID- 22384092
TI  - In vivo fluorescence lifetime imaging monitors binding of specific probes to
      cancer biomarkers.
AB  - One of the most important factors in choosing a treatment strategy for cancer is
      characterization of biomarkers in cancer cells. Particularly, recent advances in
      Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors
      show that their efficacy depends strongly on characterization of tumor
      biomarkers. Assessment of their status in individual patients would facilitate
      selection of an optimal treatment strategy, and the continuous monitoring of
      those biomarkers and their binding process to the therapy would provide a means
      for early evaluation of the efficacy of therapeutic intervention. In this study
      we have demonstrated for the first time in live animals that the fluorescence
      lifetime can be used to detect the binding of targeted optical probes to the
      extracellular receptors on tumor cells in vivo. The rationale was that
      fluorescence lifetime of a specific probe is sensitive to local environment
      and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent
      probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules
      and used our time-resolved optical system to compare the fluorescence lifetime of
      the optical probes that were bound and unbound to tumor cells in live mice. Our
      results show that the fluorescence lifetime changes in our model system delineate
      HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful
      as a specific marker of the receptor binding process, which can open a new
      paradigm in the "image and treat" concept, especially for early evaluation of the
      efficacy of the therapy.

PMID- 22384093
TI  - Acute response of peripheral blood cell to autologous hematopoietic stem cell
      transplantation in type 1 diabetic patient.
AB  - OBJECTIVE: Autologous nonmyeloablative hematopoietic stem cell transplantation
      (AHST) was the first therapeutic approach that can improve beta cell function in
      type 1 diabetic (T1D) patients. This study was designed to investigate the
      potential mechanisms involved. DESIGN AND METHODS: We applied AHST to nine T1D
      patients diagnosed within six months and analyzed the acute responses in
      peripheral blood for lymphocyte subpopulation as well as for genomic expression
      profiling at the six-month follow-up. RESULTS: We found six patients obtained
      insulin free (IF group) and three remained insulin dependent (ID group); C
      peptide production was significantly higher in IF group compared to ID group. The
      acute responses in lymphocytes at six-month follow-up include declined
      CD3(+)CD4(+), CD3(+)CD8(+) T cell population and recovered B cell, NK cell
      population in both groups but with no significant differences between the two
      groups; most immune-related genes and pathways were up-regulated in peripheral
      blood mononuclear cell (PBMC) of both groups while none of transcription factors
      for immune regulatory component were significantly changed; the IF group
      demonstrated more AHST-modified genetic events than the ID group and distinct
      pattern of top pathways, co-expression network as well as 'hub' genes (eg, TCF7
      and GZMA) were associated with each group. CONCLUSIONS: AHST could improve the
      islet function in newly diagnosed T1D patients and elimination of the islet
      specific autoreactive T cells might be one of the mechanisms involved; T1D
      patients responded differently to AHST possibly due to the distinct
      transcriptional events occurring in PBMC. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00807651.

PMID- 22384094
TI  - Loss of proliferation and antigen presentation activity following internalization
      of polydispersed carbon nanotubes by primary lung epithelial cells.
AB  - Interactions between poly-dispersed acid functionalized single walled carbon
      nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied.
      Peritoneal macrophages (PMs, known phagocytic cells) were used as positive
      controls in this study. Recovery of live cells from cultures of PLE cells and PMs
      was significantly reduced in the presence of AF-SWCNTs, in a time and dose
      dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged
      AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by
      cytochalasin D, an agent that blocks the activity of acto-myosin fibers and
      therefore the phagocytic activity of cells. Confocal microscopic studies
      confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra
      trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as
      well as alveolar macrophages. Freshly isolated PLE cells had significant cell
      division activity and cell cycling studies indicated that treatment with AF
      SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a
      previously standardized system to study BCG antigen presentation by PLE cells and
      PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen
      presentation ability of both cell types. These results show that mouse primary
      lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of
      nanotubes interfered with biological functions of PLE cells including their
      ability to present BCG antigens to sensitized T helper cells.

PMID- 22384095
TI  - The aggregation and neurotoxicity of TDP-43 and its ALS-associated 25 kDa
      fragment are differentially affected by molecular chaperones in Drosophila.
AB  - Almost all cases of sporadic amyotrophic lateral sclerosis (ALS), and some cases
      of the familial form, are characterised by the deposition of TDP-43, a member of
      a family of heteronuclear ribonucleoproteins (hnRNP). Although protein misfolding
      and deposition is thought to be a causative feature of many of the most prevalent
      neurodegenerative diseases, a link between TDP-43 aggregation and the dysfunction
      of motor neurons has yet to be established, despite many correlative
      neuropathological studies. We have investigated this relationship in the present
      study by probing the effect of altering TDP-43 aggregation behaviour in vivo by
      modulating the levels of molecular chaperones in a Drosophila model. More
      specifically, we quantify the effect of either pharmacological upregulation of
      the heat shock response or specific genetic upregulation of a small heat shock
      protein, CG14207, on the neurotoxicity of both TDP-43 and of its disease
      associated 25 kDa fragment (TDP-25) in a Drosophila model. Inhibition of the
      aggregation of TDP-43 by either method results in a partial reduction of its
      neurotoxic effects on both photoreceptor and motor neurons, whereas inhibition of
      the aggregation of TDP-25 results not only in a complete suppression of its
      toxicity but also its clearance from the brain in both neuronal subtypes studied.
      The results demonstrate, therefore, that aggregation plays a crucial role in
      mediating the neurotoxic effects of both full length and truncated TDP-43, and
      furthermore reveal that the in vivo propensity of these two proteins to aggregate
      and their susceptibility to molecular chaperone mediated clearance are quite
      distinct.

PMID- 22384096
TI  - Intracellular alkalinization induces cytosolic Ca2+ increases by inhibiting
      sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).
AB  - Intracellular pH (pHi) and Ca(2+) regulate essentially all aspects of cellular
      activities. Their inter-relationship has not been mechanistically explored. In
      this study, we used bases and acetic acid to manipulate the pHi. We found that
      transient pHi rise induced by both organic and inorganic bases, but not
      acidification induced by acid, produced elevation of cytosolic Ca(2+). The
      sources of the Ca(2+) increase are from the endoplasmic reticulum (ER) Ca(2+)
      pools as well as from Ca(2+) influx. The store-mobilization component of the
      Ca(2+) increase induced by the pHi rise was not sensitive to antagonists for
      either IP(3)-receptors or ryanodine receptors, but was due to inhibition of the
      sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), leading to depletion of the ER
      Ca(2+) store. We further showed that the physiological consequence of depletion
      of the ER Ca(2+) store by pHi rise is the activation of store-operated channels
      (SOCs) of Orai1 and Stim1, leading to increased Ca(2+) influx. Taken together,
      our results indicate that intracellular alkalinization inhibits SERCA activity,
      similar to thapsigargin, thereby resulting in Ca(2+) leak from ER pools followed
      by Ca(2+) influx via SOCs.

PMID- 22384097
TI  - 3T3 cell lines stably expressing Pax6 or Pax6(5a)--a new tool used for
      identification of common and isoform specific target genes.
AB  - Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often
      co-expressed in specific stochiometric relationship in the brain and the eye
      during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino
      acid insert in the paired domain, causing the two proteins to have different DNA
      binding specificities. Difference in functions during development is proven by
      the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a
      slightly different eye phenotype than the one described for Pax6. Whereas quite
      many Pax6 target genes have been published during the last years, few Pax6(5a)
      specific target genes have been reported on. However, target genes identified by
      Pax6 knockout studies can probably be Pax6(5a) targets as well, since this
      isoform also will be affected by the knockout. In order to identify new Pax6
      target genes, and to try to distinguish between genes regulated by Pax6 and
      Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a).
      RNA was harvested from these cell lines and used in gene expression microarrays
      where we identified a number of genes differentially regulated by Pax6 and
      Pax6(5a). A majority of these were associated with the extracellular region. By
      qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific
      target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6
      specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl
      transferases appeared to be regulated by both. Direct binding to the promoters of
      Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a
      change in morphology of the stably transfected Pax6 and Pax6(5a) cells was
      observed, and the Pax6 expressing cells were shown to have increased
      proliferation and migration capacities.

PMID- 22384098
TI  - A role for nonsense-mediated mRNA decay in plants: pathogen responses are induced
      in Arabidopsis thaliana NMD mutants.
AB  - Nonsense-mediated mRNA decay (NMD) is a conserved mechanism that targets aberrant
      mRNAs for destruction. NMD has also been found to regulate the expression of
      large numbers of genes in diverse organisms, although the biological role for
      this is unclear and few evolutionarily conserved targets have been identified.
      Expression analyses of three Arabidopsis thaliana lines deficient in NMD reveal
      that the vast majority of NMD-targeted transcripts are associated with response
      to pathogens. Congruently, NMD mutants, in which these transcripts are elevated,
      confer partial resistance to Pseudomonas syringae. These findings suggest a
      biological rationale for the regulation of gene expression by NMD in plants and
      suggest that manipulation of NMD could offer a new approach for crop protection.
      Amongst the few non-pathogen responsive NMD-targeted genes, one potential NMD
      targeted signal, the evolutionarily conserved upstream open reading frame
      (CuORF), was found to be hugely over-represented, raising the possibility that
      this feature could be used to target specific physiological mRNAs for control by
      NMD.

PMID- 22384099
TI  - Pathobiological implications of the expression of EGFR, pAkt, NF-kappaB and MIC-1
      in prostate cancer stem cells and their progenies.
AB  - The progression of prostate cancers (PCs) to locally invasive, androgen
      independent and metastatic disease states is generally associated with treatment
      resistance and disease relapse. The present study was undertaken to establish the
      possibility of using a combination of specific oncogenic products, including
      epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-kappaB)
      and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic
      targets for optimizing the management of patients with localized PC at earlier
      disease stages. The immunohistochemical and immunofluorescence data have revealed
      that the expression levels of EGFR, Ser(473)-pAkt, NF-kappaB p65 and MIC-1
      proteins were significantly enhanced in the same subset of 76 cases of prostatic
      adenocarcinoma specimens during the disease progression and these biomarkers were
      expressed in a small subpopulation of CD133(+) PC cells and the bulk tumor mass
      of CD133(-) PC cells. Importantly, all of these biomarkers were also
      overexpressed in 80-100% of 30 PC metastasis bone tissue specimens. Moreover, the
      results have indicated that the EGF-EGFR signaling pathway can provide critical
      functions for the self-renewal of side population (SP) cells endowed with stem
      cell-like features from highly invasive WPE1-NB26 cells. Of therapeutic interest,
      the targeting of EGFR, pAkt, NF-kappaB or MIC-1 was also effective at suppressing
      the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells, inducing
      disintegration of SP cell-derived prostaspheres and decreasing the viability of
      SP and non-SP WPE1-NB26 cell fractions. Also, the targeting of these oncogenic
      products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26
      cells and enhanced their sensibility to the cytotoxic effects induced by
      docetaxel. These findings suggest that the combined use of EGFR, pAkt, NF-kappaB
      and/or MIC-1 may represent promising strategies for improving the accuracy of
      current diagnostic and prognostic methods and efficacy of treatments of PC
      patients in considering the disease heterogeneity, thereby preventing PC
      progression to metastatic and lethal disease states.

PMID- 22384100
TI  - Purification and characterization of two new allergens from the venom of Vespa
      magnifica.
AB  - Due to poor diagnostic facilities and a lack of medical alertness, allergy to
      Vespa wasps may be underestimated. Few allergens have been identified from Vespa
      wasps.Possible native allergen proteins were purified from the wasp venoms (WV)
      (Vespa magnifica Smith) by gel filtration, ion exchange chromatography,
      respectively. Their sequences were determined by Edman degradation and cDNA
      cloning. Their allergenicities were assayed by enzyme-linked immunosorbent assay
      inhibition tests (ELISA-IT), immunoblots, and skin prick tests (SPTs). Their
      cross allergencities with Tab y 2 and Tab y 5 purified from the horsefly (Tabanus
      yao Macquart) were also determined. Two native allergens were identified from the
      WV, respectively. They are a 25-KDa antigen 5 protein (Ag5) (Vesp ma 5) and a 35
      KDa hyaluronidase (Vesp ma 2). They represented major allergens in Vespa
      magnifica by immunoblots and SPTs. ELISA inhibition of pooled sera IgE reactivity
      to both the WV and the horsefly salivary gland extracts (HSGE) using four
      purified allergens (Vesp ma 2, Vesp ma 5 and previously purified Tab y 2 and Tab
      y 5) was significant. Their cross allergenicities were confirmed by ELISA-IT,
      immunoblots, and SPTs. They represented the cross reactive allergens from wasp
      and horsefly and proved the so called wasp-horsefly syndrome.

PMID- 22384101
TI  - Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-beta
      mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo.
AB  - We have previously synthesized a series of hybrid compounds by linking ferulic
      acid to tacrine as multifunctional agents based on the hypotheses that
      Alzheimer's disease (AD) generates cholinergic deficiency and oxidative stress.
      Interestingly, we found that they may have potential pharmacological activities
      for treating AD. Here we report for the first time that tacrine-6-ferulic acid
      (T6FA), one of these compounds, can prevent amyloid-beta peptide (Abeta)-induced
      AD-associated pathological changes in vitro and in vivo. Our results showed that
      T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced
      aggregation of Abeta(1-40)in vitro and blocked the cell death induced by Abeta(1
      40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection
      of Abeta(1-40), T6FA significantly improved the cognitive ability along with
      increasing choline acetyltransferase and superoxide dismutase activity,
      decreasing AChE activity and malondialdehyde level. Based on our findings, we
      conclude that T6FA may be a promising multifunctional drug candidate for AD.

PMID- 22384102
TI  - A latent variable partial least squares path modeling approach to regional
      association and polygenic effect with applications to a human obesity study.
AB  - Genetic association studies are now routinely used to identify single nucleotide
      polymorphisms (SNPs) linked with human diseases or traits through single SNP
      single trait tests. Here we introduced partial least squares path modeling
      (PLSPM) for association between single or multiple SNPs and a latent trait that
      can involve single or multiple correlated measurement(s). Furthermore, the
      framework naturally provides estimators of polygenic effect by appropriately
      weighting trait-attributing alleles. We conducted computer simulations to assess
      the performance via multiple SNPs and human obesity-related traits as measured by
      body mass index (BMI), waist and hip circumferences. Our results showed that the
      associate statistics had type I error rates close to nominal level and were
      powerful for a range of effect and sample sizes. When applied to 12 candidate
      regions in data (N = 2,417) from the European Prospective Investigation of Cancer
      (EPIC)-Norfolk study, a region in FTO was found to have stronger association
      (rs7204609~rs9939881 at the first intron P = 4.29*10(-7)) than single SNP
      analysis (all with P>10(-4)) and a latent quantitative phenotype was obtained
      using a subset sample of EPIC-Norfolk (N = 12,559). We believe our method is
      appropriate for assessment of regional association and polygenic effect on a
      single or multiple traits.

PMID- 22384103
TI  - Low-replicating viruses and strong anti-viral immune response associated with
      prolonged disease control in a superinfected HIV-1 LTNP elite controller.
AB  - OBJECTIVE: To study the causes for the lack of clinical progression in a
      superinfected HIV-1 LTNP elite controller patient. METHODOLOGY AND PRINCIPAL
      FINDINGS: We studied host genetic, virological and immunological factors
      associated with viral control in a SI long term non progressor elite controller
      (LTNP-EC). The individual contained both viruses and maintained undetectable
      viral loads for >20 years and he did not express any of the described host
      genetic polymorphisms associated with viral control. None of four full-length
      gp160 recombinants derived from the LTNP-EC replicated in heterologous peripheral
      blood mononuclear cells. CTL responses after SI were maintained in two samples
      separated by 9 years and they were higher in breadth and magnitude than responses
      seen in most of 250 treatment naive patients and also 25 controller subjects. The
      LTNP-EC showed a neutralization response, against 4 of the 6 viruses analyzed,
      superior to other ECs. CONCLUSIONS: The study demonstrated that a strong and
      sustained cellular and humoral immune response and low replicating viruses are
      associated with viral control in the superinfected LTNP-EC.

PMID- 22384104
TI  - No evolutionary shift in the mating system of north American Ambrosia
      artemisiifolia (Asteraceae) following its introduction to China.
AB  - The mating system plays a key role during the process of plant invasion.
      Contemporary evolution of uniparental reproduction (selfing or asexuality) can
      relieve the challenges of mate limitation in colonizing populations by providing
      reproductive assurance. Here we examined aspects of the genetics of colonization
      in Ambrosia artemisiifolia, a North American native that is invasive in China.
      This species has been found to possess a strong self-incompatibility system and
      have high outcrossing rates in North America and we examined whether there has
      been an evolutionary shift towards the dependence on selfing in the introduced
      range. Specifically, we estimated outcrossing rates in one native and five
      invasive populations and compared levels of genetic diversity between North
      America and China. Based on six microsatellite loci we found that, like the
      native North American population, all five Chinese populations possessed a
      completely outcrossing mating system. The estimates of paternity correlations
      were low, ranging from 0.028-0.122, which suggests that populations possessed ~8
      36 pollen donor parents contributing to each maternal plant in the invasive
      populations. High levels of genetic diversity for both native and invasive
      populations were found with the unbiased estimate of gene diversity ranging from
      0.262-0.289 for both geographic ranges based on AFLP markers. Our results
      demonstrate that there has been no evolutionary shift from outcrossing to selfing
      during A. artemisiifolia's invasion of China. Furthermore, high levels of genetic
      variation in North America and China indicate that there has been no erosion of
      genetic variance due to a bottleneck during the introduction process. We suggest
      that the successful invasion of A. artemisiifolia into Asia was facilitated by
      repeated introductions from multiple source populations in the native range
      creating a diverse gene pool within Chinese populations.

PMID- 22384105
TI  - Mood modulates auditory laterality of hemodynamic mismatch responses during
      dichotic listening.
AB  - Hemodynamic mismatch responses can be elicited by deviant stimuli in a sequence
      of standard stimuli even during cognitive demanding tasks. Emotional context is
      known to modulate lateralized processing. Right-hemispheric negative emotion
      processing may bias attention to the right and enhance processing of right-ear
      stimuli. The present study examined the influence of induced mood on lateralized
      pre-attentive auditory processing of dichotic stimuli using functional magnetic
      resonance imaging (fMRI). Faces expressing emotions (sad/happy/neutral) were
      presented in a blocked design while a dichotic oddball sequence with consonant
      vowel (CV) syllables in an event-related design was simultaneously administered.
      Twenty healthy participants were instructed to feel the emotion perceived on the
      images and to ignore the syllables. Deviant sounds reliably activated bilateral
      auditory cortices and confirmed attention effects by modulation of visual
      activity. Sad mood induction activated visual, limbic and right prefrontal areas.
      A lateralization effect of emotion-attention interaction was reflected in a
      stronger response to right-ear deviants in the right auditory cortex during sad
      mood. This imbalance of resources may be a neurophysiological correlate of
      laterality in sad mood and depression. Conceivably, the compensatory right
      hemispheric enhancement of resources elicits increased ipsilateral processing.

PMID- 22384106
TI  - Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis.
AB  - Interleukin-7 (IL-7) is a major survival factor for mature T cells. Therefore,
      the degree of IL-7 availability determines the size of the peripheral T cell pool
      and regulates T cell homeostasis. Here we provide evidence that IL-7 also
      regulates the homeostasis of intestinal epithelial cells (IEC), colon function
      and the composition of the commensal microflora. In the colon of T cell
      deficient, lymphopenic mice, IL-7-producing IEC accumulate. IEC hyperplasia can
      be blocked by IL-7-consuming T cells or the inactivation of the IL-7/IL-7R
      signaling pathway. However, the blockade of the IL-7/IL-7R signaling pathway
      renders T cell-deficient mice more sensitive to chemically-induced IEC damage and
      subsequent colitis. In summary, our data demonstrate that IL-7 promotes IEC
      hyperplasia under lymphopenic conditions. Under non-lymphopenic conditions,
      however, T cells consume IL-7 thereby limiting IEC expansion and survival. Hence,
      the degree of IL-7 availability regulates both, T cell and IEC homeostasis.

PMID- 22384107
TI  - Resistance to DDT and pyrethroids and increased kdr mutation frequency in An.
      gambiae after the implementation of permethrin-treated nets in Senegal.
AB  - INTRODUCTION: The aim of this study was to evaluate the susceptibility to
      insecticides of An. gambiae mosquitoes sampled in Dielmo (Senegal), in 2010, 2
      years after the implementation of Long Lasting Insecticide-treated Nets (LLINs)
      and to report the evolution of kdr mutation frequency from 2006 to 2010. METHODS:
      WHO bioassay susceptibility tests to 6 insecticides were performed on adults F0,
      issuing from immature stages of An. gambiae s.l., sampled in August 2010. Species
      and molecular forms as well as the presence of L1014F and L1014S kdr mutations
      were assessed by PCR. Longitudinal study of kdr mutations was performed on adult
      mosquitoes sampled monthly by night landing catches from 2006 to 2010. FINDINGS:
      No specimen studied presented the L1014S mutation. During the longitudinal study,
      L1014F allelic frequency rose from 2.4% in year before the implementation of
      LLINs to 4.6% 0-12 months after and 18.7% 13-30 months after. In 2010, An.
      gambiae were resistant to DDT, Lambda-cyhalothrin, Deltamethrin and Permethrin
      (mortality rates ranging from 46 to 63%) but highly susceptible to Fenitrothion
      and Bendiocarb (100% mortality). There was significantly more RR genotype among
      An. gambiae surviving exposure to DDT or Pyrethroids. An. arabiensis represented
      3.7% of the sampled mosquitoes (11/300) with no kdr resistance allele detected.
      An. gambiae molecular form M represented 29.7% of the mosquitoes with, among
      them, kdr genotypes SR (18%) and SS (82%). An. gambiae molecular form S
      represented 66% of the population with, among them, kdr genotype SS (33.3%), SR
      (55.6%) and RR (11.1%). Only 2 MS hybrid mosquitoes were sampled and presented SS
      kdr genotype. CONCLUSION: Biological evidence of resistance to DDT and
      pyrethroids was detected among An. gambiae mosquitoes in Dielmo (Senegal) within
      24 months of community use of LLINs. Molecular identification of L1014F mutation
      indicated that target site resistance increased after the implementation of
      LLINs.

PMID- 22384108
TI  - Correlated genetic and ecological diversification in a widespread southern
      African horseshoe bat.
AB  - The analysis of molecular data within a historical biogeographical framework,
      coupled with ecological characteristics can provide insight into the processes
      driving diversification. Here we assess the genetic and ecological diversity
      within a widespread horseshoe bat Rhinolophus clivosus sensu lato with specific
      emphasis on the southern African representatives which, although not currently
      recognized, were previously described as a separate species R. geoffroyi
      comprising four subspecies. Sequence divergence estimates of the mtDNA control
      region show that the southern African representatives of R. clivosus s.l. are as
      distinct from samples further north in Africa than they are from R.
      ferrumequinum, the sister-species to R. clivosus. Within South Africa, five
      genetically supported geographic groups exist and these groups are corroborated
      by echolocation and wing morphology data. The groups loosely correspond to the
      distributions of the previously defined subspecies and Maxent modelling shows a
      strong correlation between the detected groups and ecoregions. Based on molecular
      clock calibrations, it is evident that climatic cycling and related vegetation
      changes during the Quaternary may have facilitated diversification both
      genetically and ecologically.

PMID- 22384109
TI  - Aptamers as a sensitive tool to detect subtle modifications in therapeutic
      proteins.
AB  - Therapeutic proteins are derived from complex expression/production systems,
      which can result in minor conformational changes due to preferential codon usage
      in different organisms, post-translational modifications, etc. Subtle
      conformational differences are often undetectable by bioanalytical methods but
      can sometimes profoundly impact the safety, efficacy and stability of products.
      Numerous bioanalytical methods exist to characterize the primary structure of
      proteins, post translational modifications; protein-substrate/protein/protein
      interactions and functional bioassays are available for most proteins that are
      developed as products. There are however few analytical techniques to detect
      changes in the tertiary structure of proteins suitable for use during drug
      development and quality control. For example, x-ray crystallography and NMR are
      impractical for routine use and do not capture the heterogeneity of the product.
      Conformation-sensitive antibodies can be used to map proteins. However the
      development of antibodies to represent sufficient epitopes can be challenging.
      Other limitations of antibodies include limited supply, high costs, heterogeneity
      and batch to batch variations in titer. Here we provide proof-of-principle that
      DNA aptamers to thrombin can be used as surrogate antibodies to characterize
      conformational changes. We show that aptamers can be used in assays using either
      an ELISA or a label-free platform to characterize different thrombin products. In
      addition we replicated a heat-treatment procedure that has previously been shown
      to not affect protein activity but can result in conformational changes that have
      serious adverse consequences. We demonstrate that a panel of aptamers (but not an
      antibody) can detect changes in the proteins even when specific activity is
      unaffected. Our results indicate a novel approach to monitor even small changes
      in the conformation of proteins which can be used in a routine drug-development
      and quality control setting. The technique can provide an early warning of
      structural changes during the manufacturing process that could have consequential
      outcomes downstream.

PMID- 22384110
TI  - Functional desaturase Fads1 (Delta5) and Fads2 (Delta6) orthologues evolved
      before the origin of jawed vertebrates.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA),
      eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components
      of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA
      and DHA occurs from precursor dietary essential fatty acids such as linoleic and
      alpha-linolenic acid through elongation and Delta5 and Delta6 desaturations. With
      respect to desaturation activities some noteworthy differences have been noted in
      vertebrate classes. In mammals, the Delta5 activity is allocated to the Fads1
      gene, while Fads2 is a Delta6 desaturase. In contrast, teleosts show distinct
      combinations of desaturase activities (e.g. bifunctional or separate Delta5 and
      Delta6 desaturases) apparently allocated to Fads2-type genes. To determine the
      timing of Fads1-Delta5 and Fads2-Delta6 evolution in vertebrates we used a
      combination of comparative and functional genomics with the analysis of key
      phylogenetic species. Our data show that Fads1 and Fads2 genes with Delta5 and
      Delta6 activities respectively, evolved before gnathostome radiation, since the
      catshark Scyliorhinus canicula has functional orthologues of both gene families.
      Consequently, the loss of Fads1 in teleosts is a secondary episode, while the
      existence of Delta5 activities in the same group most likely occurred through
      independent mutations into Fads2 type genes. Unexpectedly, we also establish that
      events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a
      fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian
      genomes. Our findings enlighten the history of a crucially important gene family
      in vertebrate fatty acid metabolism and physiology and provide an explanation of
      how observed lineage-specific gene duplications, losses and diversifications
      might be linked to habitat-specific food web structures in different environments
      and over geological timescales.

PMID- 22384111
TI  - Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via
      modulation of PKA and ERK signaling.
AB  - Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce
      biologically active compounds that can modulate host mucosal immunity.
      Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were
      unknown. A combined metabolomics and bacterial genetics strategy was utilized to
      identify small compound(s) produced by L. reuteri that were TNF-inhibitory.
      Hydrophilic interaction liquid chromatography-high performance liquid
      chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and
      HILIC-HPLC fraction composition was determined by NMR and mass spectrometry
      analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC
      fractions. Histamine is produced from L-histidine via histidine decarboxylase by
      some fermentative bacteria including lactobacilli. Targeted mutagenesis of each
      gene present in the histidine decarboxylase gene cluster in L. reuteri 6475
      demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA),
      histidine/histamine antiporter (hdcP), and hdcB in production of the TNF
      inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived
      histamine was investigated using Toll-like receptor 2 (TLR2)-activated human
      monocytoid cells. Bacterial histamine suppressed TNF production via activation of
      the H(2) receptor. Histamine from L. reuteri 6475 stimulated increased levels of
      cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A
      (PKA) and resulted in suppression of TNF production by transcriptional
      regulation. In summary, a component of the gut microbiome, L. reuteri, is able to
      convert a dietary component, L-histidine, into an immunoregulatory signal,
      histamine, which suppresses pro-inflammatory TNF production. The identification
      of bacterial bioactive metabolites and their corresponding mechanisms of action
      with respect to immunomodulation may lead to improved anti-inflammatory
      strategies for chronic immune-mediated diseases.

PMID- 22384112
TI  - Identification of novel avian influenza virus derived CD8+ T-cell epitopes.
AB  - Avian influenza virus (AIV) infection is a continuing threat to both humans and
      poultry. Influenza virus specific CD8+ T cells are associated with protection
      against homologous and heterologous influenza strains. In contrast to what has
      been described for humans and mice, knowledge on epitope-specific CD8+ T cells in
      chickens is limited. Therefore, we set out to identify AIV-specific CD8+ T-cell
      epitopes. Epitope predictions based on anchor residues resulted in 33 candidate
      epitopes. MHC I inbred chickens were infected with a low pathogenic AIV strain
      and sacrificed at 5, 7, 10 and 14 days post infection (dpi). Lymphocytes isolated
      from lung, spleen and blood were stimulated ex vivo with AIV-specific pooled or
      individual peptides and the production of IFNgamma was determined by ELIspot.
      This resulted in the identification of 12 MHC B12-restricted, 3 B4-restricted and
      1 B19-restricted AIV- specific CD8+ T-cell epitopes. In conclusion, we have
      identified novel AIV-derived CD8+ T-cell epitopes for several inbred chicken
      strains. This knowledge can be used to study the role of CD8+ T cells against AIV
      infection in a natural host for influenza, and may be important for vaccine
      development.

PMID- 22384113
TI  - Probing the behaviors of gold nanorods in metastatic breast cancer cells based on
      UV-vis-NIR absorption spectroscopy.
AB  - In this work, behaviors of positively-charged AuNRs in a highly metastatic tumor
      cell line MDA-MB-231 are examined based on UV-vis-NIR absorption spectroscopy in
      combination with inductively coupled plasma mass spectrometry (ICP-MS),
      transmission electron microscopy (TEM) and dark-field microscopic observation. It
      is found that characteristic surface plasmon resonance (SPR) peaks of AuNRs can
      be detected using spectroscopic method within living cells that have taken up
      AuNRs. The peak area of transverse SPR band is shown to be proportionally related
      to the amount of AuNRs in the cells determined with ICP-MS, which suggests a
      facile and real time quantification method for AuNRs in living cells. The shape
      of longitudinal SPR band in UV-vis-NIR spectrum reflects the aggregation state of
      AuNRs in the cells during the incubation period, which is proved by TEM and
      microscopic observations. Experimental results reveal that AuNRs are internalized
      by the cells rapidly; the accumulation, distribution and aggregation of AuNRs in
      the cells compartments are time and dose dependent. The established spectroscopic
      analysis method can not only monitor the behaviors of AuNRs in living cells but
      may also be helpful in choosing the optimum laser stimulation wavelength for anti
      tumor thermotherapy.

PMID- 22384114
TI  - Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells
      is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A.
AB  - In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can
      play an immunoregulatory role by eliminating chronically activated leukocytes.
      Indirect evidence suggests that NK cells may also be immunoregulatory in humans.
      Two subsets of human NK cells can be phenotypically distinguished as
      CD16(+)CD56(dim) and CD16(dim/-)CD56(bright). An expansion in the CD56(bright) NK
      cell subset has been associated with clinical responses to therapy in various
      autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo.
      Here we compared the regulation of activated human CD4(+) T cells by CD56(dim)
      and CD56(bright) autologous NK cells in vitro. Both subsets efficiently killed
      activated, but not resting, CD4(+) T cells. The activating receptor NKG2D, as
      well as the integrin LFA-1 and the TRAIL pathway, played important roles in this
      process. Degranulation by NK cells towards activated CD4(+) T cells was enhanced
      by IL-2, IL-15, IL-12+IL-18 and IFN-alpha. Interestingly, IL-7 and IL-21
      stimulated degranulation by CD56(bright) NK cells but not by CD56(dim) NK cells.
      NK cell killing of activated CD4(+) T cells was suppressed by HLA-E on CD4(+) T
      cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK
      cell receptor enhanced NK cell degranulation. This study provides new insight
      into CD56(dim) and CD56(bright) NK cell-mediated elimination of activated
      autologous CD4(+) T cells, which potentially may provide an opportunity for
      therapeutic treatment of chronic inflammation.

PMID- 22384115
TI  - Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro.
AB  - Chemotherapy is a primary treatment for cancer, but its efficacy is often limited
      by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the
      non-specific toxicity of chemotherapy by selectively directing anticancer drugs
      to tumor cells. MUC1 protein is an attractive target for tumor-specific drug
      delivery owning to its overexpression in most adenocarcinomas. In this study, a
      novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin
      (Dox) to cancer cells. We developed an 86-base DNA aptamer (MA3) that bound to a
      peptide epitope of MUC1 with a K(d) of 38.3 nM and minimal cross reactivity to
      albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing
      models, MA3 was found to preferentially bind to MUC1-positive but not MUC1
      negative cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by
      intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found
      capable of carrying doxorubicin into MUC1-positive tumor cells, while
      significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox
      retained the efficacy of doxorubicin against MUC1-positive tumor cells, but
      lowered the toxicity to MUC1-negative cells (P<0.01). The results suggest that
      the MUC1 aptamer may have potential utility as a targeting ligand for selective
      delivery of cytotoxic agent to MUC1-expressing tumors.

PMID- 22384116
TI  - Herbivory by a Phloem-feeding insect inhibits floral volatile production.
AB  - There is extensive knowledge on the effects of insect herbivory on volatile
      emission from vegetative tissue, but little is known about its impact on floral
      volatiles. We show that herbivory by phloem-feeding aphids inhibits floral
      volatile emission in white mustard Sinapis alba measured by gas chromatographic
      analysis of headspace volatiles. The effect of the Brassica specialist aphid
      Lipaphis erysimi was stronger than the generalist aphid Myzus persicae and
      feeding by chewing larvae of the moth Plutella xylostella caused no reduction in
      floral volatile emission. Field observations showed no effect of L. erysimi
      mediated floral volatile emission on the total number of flower visits by
      pollinators. Olfactory bioassays suggested that although two aphid natural
      enemies could detect aphid inhibition of floral volatiles, their olfactory
      orientation to infested plants was not disrupted. This is the first demonstration
      that phloem-feeding herbivory can affect floral volatile emission, and that the
      outcome of interaction between herbivory and floral chemistry may differ
      depending on the herbivore's feeding mode and degree of specialisation. The
      findings provide new insights into interactions between insect herbivores and
      plant chemistry.

PMID- 22384117
TI  - Heterogeneity in genetic diversity among non-coding loci fails to fit neutral
      coalescent models of population history.
AB  - Inferring aspects of the population histories of species using coalescent
      analyses of non-coding nuclear DNA has grown in popularity. These inferences,
      such as divergence, gene flow, and changes in population size, assume that
      genetic data reflect simple population histories and neutral evolutionary
      processes. However, violating model assumptions can result in a poor fit between
      empirical data and the models. We sampled 22 nuclear intron sequences from at
      least 19 different chromosomes (a genomic transect) to test for deviations from
      selective neutrality in the gadwall (Anas strepera), a Holarctic duck. Nucleotide
      diversity among these loci varied by nearly two orders of magnitude (from 0.0004
      to 0.029), and this heterogeneity could not be explained by differences in
      substitution rates alone. Using two different coalescent methods to infer models
      of population history and then simulating neutral genetic diversity under these
      models, we found that the observed among-locus heterogeneity in nucleotide
      diversity was significantly higher than expected for these simple models.
      Defining more complex models of population history demonstrated that a pre
      divergence bottleneck was also unlikely to explain this heterogeneity. However,
      both selection and interspecific hybridization could account for the
      heterogeneity observed among loci. Regardless of the cause of the deviation, our
      results illustrate that violating key assumptions of coalescent models can
      mislead inferences of population history.

PMID- 22384118
TI  - Integrative genomic analysis reveals extended germline homozygosity with lung
      cancer risk in the PLCO cohort.
AB  - Susceptibility to common cancers is multigenic resulting from low-to-high
      penetrance predisposition-factors and environmental exposure. Genomic studies
      suggest germline homozygosity as a novel low-penetrance factor contributing to
      common cancers. We hypothesized that long homozygous regions (tracts-of
      homozygosity [TOH]) harbor tobacco-dependent and independent lung-cancer
      predisposition (or protection) genes. We performed in silico genome-wide SNP
      array-based analysis of lung-cancer patients of European-ancestry from the PLCO
      screening-trial cohort to identify TOH regions amongst 788 cancer-cases and 830
      ancestry-matched controls. Association analyses was then performed between
      presence of lung cancer and common(c)TOHs (operationally defined as 10 or more
      subjects sharing >=100 identical homozygous calls), aTOHs (allelically-matched
      groups within a cTOH), demographics and tobacco-exposure. Finally, integration of
      significant c/aTOH with transcriptome was performed to functionally-map lung
      cancer risk-genes. After controlling for demographics and smoking, we identified
      7 cTOHs and 5 aTOHs associated with lung cancer (adjusted p<0.01). Three cTOHs
      were over-represented in cases over controls (OR = 1.75-2.06, p = 0.007-0.001),
      whereas 4 were under-represented (OR = 0.28-0.69, p = 0.006-0.001). Interaction
      between smoking status and cTOH3/aTOH2 (2p16.3-2p16.1) was observed (adjusted
      p<0.03). The remaining significant aTOHs have ORs 0.23-0.50 (p = 0.004-0.006) and
      2.95-3.97 (p = 0.008-0.001). After integrating significant cTOH/aTOHs with
      publicly-available lung-cancer transcriptome datasets followed by filtering based
      on lung cancer and its relevant pathways revealed 9 putative predisposing genes
      (p<0.0001). In conclusion, differentially-distributed cTOH/aTOH genomic variants
      between cases and controls harbor sets of plausible differentially-expressed
      genes accounting for the complexity of lung-cancer predisposition.

PMID- 22384119
TI  - First dating of a recombination event in mammalian tick-borne flaviviruses.
AB  - The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated
      with important human and animal diseases such as encephalitis and hemorrhagic
      fever. In contrast to mosquito-borne flaviviruses where recombination events are
      frequent, the evolutionary dynamic within the MTBFG was believed to be
      essentially clonal. This assumption was challenged with the recent report of
      several homologous recombinations within the Tick-borne encephalitis virus
      (TBEV). We performed a thorough analysis of publicly available genomes in this
      group and found no compelling evidence for the previously identified
      recombinations. However, our results show for the first time that demonstrable
      recombination (i.e., with large statistical support and strong phylogenetic
      evidences) has occurred in the MTBFG, more specifically within the Louping ill
      virus lineage. Putative parents, recombinant strains and breakpoints were further
      tested for statistical significance using phylogenetic methods. We investigated
      the time of divergence between the recombinant and parental strains in a Bayesian
      framework. The recombination was estimated to have occurred during a window of
      282 to 76 years before the present. By unravelling the temporal setting of the
      event, we adduce hypotheses about the ecological conditions that could account
      for the observed recombination.

PMID- 22384120
TI  - Metabolomics with LC-QTOF-MS permits the prediction of disease stage in aortic
      abdominal aneurysm based on plasma metabolic fingerprint.
AB  - Abdominal aortic aneurysm (AAA) is a permanent and localized aortic dilation,
      defined as aortic diameter >=3 cm. It is an asymptomatic but potentially fatal
      condition because progressive enlargement of the abdominal aorta is spontaneously
      evolving towards rupture.Biomarkers may help to explain pathological processes of
      AAA expansion, and allow us to find novel therapeutic strategies or to determine
      the efficiency of current therapies. Metabolomics seems to be a good approach to
      find biomarkers of AAA. In this study, plasma samples of patients with large AAA,
      small AAA, and controls were fingerprinted with LC-QTOF-MS. Statistical analysis
      was used to compare metabolic fingerprints and select metabolites that showed a
      significant change. Results presented here reveal that LC-QTOF-MS based
      fingerprinting of plasma from AAA patients is a very good technique to
      distinguish small AAA, large AAA, and controls. With the use of validated PLS-DA
      models it was possible to classify patients according to the disease stage and
      predict properly the stage of additional AAA patients. Identified metabolites
      indicate a role for sphingolipids, lysophospholipids, cholesterol metabolites,
      and acylcarnitines in the development and progression of AAA. Moreover,
      guanidinosuccinic acid, which mimics nitric oxide in terms of its vasodilatory
      action, was found as a strong marker of large AAA.

PMID- 22384121
TI  - Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock.
AB  - Throughout the day, clock proteins synchronize changes in animal physiology
      (e.g., wakefulness and appetite) with external cues (e.g., daylight and food). In
      vertebrates, both casein kinase 1 delta and epsilon (CK1delta and CK1epsilon)
      regulate these circadian changes by phosphorylating other core clock proteins. In
      addition, CK1 can regulate circadian-dependent transcription in a non-catalytic
      manner, however, the mechanism is unknown. Furthermore, the extent of functional
      redundancy between these closely related kinases is debated. To further advance
      knowledge about CK1delta and CK1epsilon mechanisms of action in the biological
      clock, we first carried out proteomic analysis of both kinases in human cells.
      Next, we tested interesting candidates in a cell-based circadian readout which
      resulted in the discovery of PROHIBITIN 2 (PHB2) as a modulator of period length.
      Decreasing the expression of PHB2 increases circadian-driven transcription, thus
      revealing PHB2 acts as an inhibitor in the molecular clock. While stable binding
      of PHB2 to either kinase was not detected, knocking down CK1epsilon expression
      increases PHB2 protein levels and, unexpectedly, knocking down CK1delta decreases
      PHB2 transcript levels. Thus, isolating CK1 protein complexes led to the
      identification of PHB2 as an inhibitor of circadian transcription. Furthermore,
      we show that CK1delta and CK1epsilon differentially regulate the expression of
      PHB2.

PMID- 22384122
TI  - Genetic ablation of Pannexin1 protects retinal neurons from ischemic injury.
AB  - Pannexin1 (Panx1) forms large nonselective membrane channel that is implicated in
      paracrine and inflammatory signaling. In vitro experiments suggested that Panx1
      could play a key role in ischemic death of hippocampal neurons. Since retinal
      ganglion cells (RGCs) express high levels of Panx1 and are susceptible to
      ischemic induced injury, we hypothesized that Panx1 contributes to rapid and
      selective loss of these neurons in ischemia. To test this hypothesis, we induced
      experimental retinal ischemia followed by reperfusion in live animals with the
      Panx1 channel genetically ablated either in the entire mouse (Panx1 KO), or only
      in neurons using the conditional knockout (Panx1 CKO) technology. Here we report
      that two distinct neurotoxic processes are induced in RGCs by ischemia in the
      wild type mice but are inactivated in Panx1KO and Panx1 CKO animals. First, the
      post-ischemic permeation of RGC plasma membranes is suppressed, as assessed by
      dye transfer and calcium imaging assays ex vivo and in vitro. Second, the
      inflammasome-mediated activation of caspase-1 and the production of interleukin
      1beta in the Panx1 KO retinas are inhibited. Our findings indicate that post
      ischemic neurotoxicity in the retina is mediated by previously uncharacterized
      pathways, which involve neuronal Panx1 and are intrinsic to RGCs. Thus, our work
      presents the in vivo evidence for neurotoxicity elicited by neuronal Panx1, and
      identifies this channel as a new therapeutic target in ischemic pathologies.

PMID- 22384123
TI  - Predictors on delay of initial health-seeking in new pulmonary tuberculosis cases
      among migrants population in East China.
AB  - OBJECTIVES: To determine the length of delay in initial health-seeking in new
      pulmonary tuberculosis (PTB) cases among migrant population in the eastern part
      of China, and factors associated with it. METHODS: A cross-sectional study was
      conducted using a structured questionnaire in six counties in Shanghai, Guangdong
      and Jiangsu from May to October, 2008, to estimate the extent and factors
      responsible for delayed initial health-seeking of the new PTB cases. The interval
      between self-reported onset of TB symptoms and date of first attendance at any
      medical institution was determined. More than the median duration was defined as
      delayed health-seeking. RESULTS: A total of 323 new migrant PTB patients
      participated in the study. Only 6.5% had medical insurance. The median and mean
      durations to initial health-seeking were respectively 10 and 31 days. There was
      no significant association between socio-demographic factors and delayed initial
      health-seeking. Average monthly working days >24 (AOR, 1.61; 95% CI, 1.03-2.51),
      and hemoptysis or bloody sputum (AOR, 0.48; 95% CI, 0.28-0.85) were significantly
      associated with delayed initial health-seeking. CONCLUSIONS: Interventions to
      improve health seeking behavior among the migrant population in China must focus
      on strengthening their labor, medical security and health education.

PMID- 22384124
TI  - Phenotypic detection of clonotypic B cells in multiple myeloma by specific
      immunoglobulin ligands reveals their rarity in multiple myeloma.
AB  - In multiple myeloma, circulating "clonotypic" B cells, that express the
      immunoglobulin rearrangement of the malignant plasma cell clone, can be
      indirectly detected by PCR. Their role as potential "feeder" cells for the
      malignant plasma cell pool remains controversial. Here we established for the
      first time an approach that allows direct tracking of such clonotypic cells by
      labeling with patient-specific immunoglobulin ligands in 15 patients with
      myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood
      or bone marrow by PCR. Epitope-mimicking peptides from random libraries were
      selected on each patient's individual immunoglobulin and used as ligands to trace
      cells expressing the idiotypic immunoglobulin on their surface. We established a
      flow cytometry and immunofluorescence protocol to track clonotypic B cells and
      validated it in two independent monoclonal B cell systems. Using this method, we
      found clonotypic B cells in only one out of 15 myeloma patients. In view of the
      assay's validated sensitivity level of 10(-3), this surprising data suggests that
      the abundance of such cells has been vastly overestimated in the past and that
      they apparently represent a very rare population in myeloma. Our novel tracing
      approach may open perspectives to isolate and analyze clonotypic B cells and
      determine their role in myeloma pathobiology.

PMID- 22384125
TI  - In vitro maturation of dopaminergic neurons derived from mouse embryonic stem
      cells: implications for transplantation.
AB  - The obvious motor symptoms of Parkinson's disease result from a loss of
      dopaminergic neurons from the substantia nigra. Embryonic stem cell-derived
      neural progenitor or precursor cells, adult neurons and fetal midbrain tissue
      have all been used to replace dying dopaminergic neurons. Transplanted cell
      survival is compromised by factors relating to the new environment, for example;
      hypoxia, mechanical trauma and excitatory amino acid toxicity. In this study we
      investigate, using live-cell fluorescence Ca(2+) and Cl(-) imaging, the
      functional properties of catecholaminergic neurons as they mature. We also
      investigate whether GABA has the capacity to act as a neurotoxin early in the
      development of these neurons. From day 13 to day 21 of differentiation [Cl(-)](i)
      progressively dropped in tyrosine hydroxylase positive (TH(+)) neurons from 56.0
      (95% confidence interval, 55.1, 56.9) mM to 6.9 (6.8, 7.1) mM. At days 13 and 15
      TH(+) neurons responded to GABA (30 uM) with reductions in intracellular Cl(-)
      ([Cl(-)](i)); from day 21 the majority of neurons responded to GABA (30 uM) with
      elevations of [Cl(-)](i). As [Cl(-)](i) reduced, the ability of GABA (30 uM) to
      elevate intracellular Ca(2+) ([Ca(2+)](i)) did also. At day 13 of differentiation
      a three hour exposure to GABA (30 uM) or L-glutamate (30 uM) increased the number
      of midbrain dopaminergic (TH(+) and Pitx3(+)) neurons labeled with the membrane
      impermeable nuclear dye TOPRO-3. By day 23 cultures were resistant to the effects
      of both GABA and L-glutamate. We believe that neuronal susceptibility to amino
      acid excitotoxicity is dependent upon neuronal maturity, and this should be
      considered when isolating cells for transplantation studies.

PMID- 22384126
TI  - Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      characterized by a progressive loss of lower motor neurons in the spinal cord.
      The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin
      signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is
      currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in
      the brain and spinal cord, and our prior studies have shown that Ex-4 is
      neuroprotective in several neurodegenerative disease rodent models, including
      stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex
      4 may provide neuroprotective activity in ALS, and hence characterized Ex-4
      actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A
      mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells,
      elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective,
      protecting cells from hydrogen peroxide-induced oxidative stress and
      staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant
      SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic
      factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant
      mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage
      disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice
      treated with Ex-4 showed improved glucose tolerance and normalization of
      behavior, as assessed by running wheel, compared to control ALS mice.
      Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal
      cord; immunohistochemical analysis demonstrated the rescue of neuronal markers,
      such as ChAT, associated with motor neurons. Together, our results suggest that
      GLP-1 receptor agonists warrant further evaluation to assess whether their
      neuroprotective potential is of therapeutic relevance in ALS.

PMID- 22384127
TI  - A crosstalk between the Smad and JNK signaling in the TGF-beta-induced epithelial
      mesenchymal transition in rat peritoneal mesothelial cells.
AB  - Transforming growth factor beta (TGF-beta) induces the process of epithelial
      mesenchymal transition (EMT) through the Smad and JNK signaling. However, it is
      unclear how these pathways interact in the TGF-beta1-induced EMT in rat
      peritoneal mesothelial cells (RPMCs). Here, we show that inhibition of JNK
      activation by introducing the dominant-negative JNK1 gene attenuates the TGF
      beta1-down-regulated E-cadherin expression, and TGF-beta1-up-regulated alpha-SMA,
      Collagen I, and PAI-1 expression, leading to the inhibition of EMT in primarily
      cultured RPMCs. Furthermore, TGF-beta1 induces a bimodal JNK activation with
      peaks at 10 minutes and 12 hours post treatment in RPMCs. In addition, the
      inhibition of Smad3 activation by introducing a Smad3 mutant mitigates the TGF
      beta1-induced second wave, but not the first wave, of JNK1 activation in RPMCs.
      Moreover, the inhibition of JNK1 activation prevents the TGF-beta1-induced Smad3
      activation and nuclear translocation, and inhibition of the TGF-beta1-induced
      second wave of JNK activation greatly reduced TGF-beta1-induced EMT in RPMCs.
      These data indicate a crosstalk between the JNK1 and Samd3 pathways during the
      TGF-beta1-induced EMT and fibrotic process in RPMCs. Therefore, our findings may
      provide new insights into understanding the regulation of the TGF-beta1-related
      JNK and Smad signaling in the development of fibrosis.

PMID- 22384128
TI  - Use of a generalized additive model to investigate key abiotic factors affecting
      microcystin cellular quotas in heavy bloom areas of Lake Taihu.
AB  - Lake Taihu is the third largest freshwater lake in China and is suffering from
      serious cyanobacterial blooms with the associated drinking water contamination by
      microcystin (MC) for millions of citizens. So far, most studies on MCs have been
      limited to two small bays, while systematic research on the whole lake is
      lacking. To explain the variations in MC concentrations during cyanobacterial
      bloom, a large-scale survey at 30 sites across the lake was conducted monthly in
      2008. The health risks of MC exposure were high, especially in the northern area.
      Both Microcystis abundance and MC cellular quotas presented positive correlations
      with MC concentration in the bloom seasons, suggesting that the toxic risks
      during Microcystis proliferations were affected by variations in both Microcystis
      density and MC production per Microcystis cell. Use of a powerful predictive
      modeling tool named generalized additive model (GAM) helped visualize significant
      effects of abiotic factors related to carbon fixation and proliferation of
      Microcystis (conductivity, dissolved inorganic carbon (DIC), water temperature
      and pH) on MC cellular quotas from recruitment period of Microcystis to the bloom
      seasons, suggesting the possible use of these factors, in addition to Microcystis
      abundance, as warning signs to predict toxic events in the future. The
      interesting relationship between macrophytes and MC cellular quotas of
      Microcystis (i.e., high MC cellular quotas in the presence of macrophytes) needs
      further investigation.

PMID- 22384129
TI  - Psychometric properties of the Danish Strength and Difficulties Questionnaire:
      the SDQ assessed for more than 70,000 raters in four different cohorts.
AB  - BACKGROUND: The Strength and Difficulties Questionnaire (SDQ) is a brief
      behavioural five factor instrument developed to assess emotional and behavioural
      problems in children and adolescents. The aim of the current study was to
      evaluate the psychometric properties for parent and teacher ratings in the Danish
      version of SDQ for different age groups of boys and girls. METHODS: The Danish
      versions of the SDQ were distributed to a total of 71,840 parent and teacher
      raters of 5-, 7- and 10- to 12-year-old children included in four large scale
      Danish cohorts. The internal reliability was assessed and exploratory factor
      analyses were carried out to replicate the originally proposed five factor
      structure. Mean scores and percentiles were examined in order to differentiate
      between low, medium and high levels of emotional and behavioural difficulties.
      RESULTS: The original five factor structure could be substantially confirmed. The
      Conduct items however did not solely load on the proposed Conduct scale and the
      Conduct scale was further contaminated by non-conduct items. Positively worded
      items tended to load on the Prosocial scale. This was more so the case for
      teachers than for parents. Parent and teacher means and percentiles were found to
      be lower compared to British figures but similar to or only slightly lower than
      those found in the other Nordic countries. The percentiles for girls were
      generally lower than for boys, markedly so for the teacher hyperactivity ratings.
      CONCLUSIONS: The study supports the usefulness of the SDQ as a screening tool for
      boys and girls across age groups and raters in the general Danish population.

PMID- 22384130
TI  - Structural and functional analysis of validoxylamine A 7'-phosphate synthase ValL
      involved in validamycin A biosynthesis.
AB  - Validamycin A (Val-A) is an effective antifungal agent widely used in Asian
      countries as crop protectant. Validoxylamine A, the core structure and
      intermediate of Val-A, consists of two C(7)-cyclitol units connected by a rare C
      N bond. In the Val-A biosynthetic gene cluster in Streptomyces hygroscopicus
      5008, the ORF valL was initially annotated as a validoxylamine A 7'
      phosphate(V7P) synthase, whose encoded 497-aa protein shows high similarity with
      trehalose 6-phosphate(T6P) synthase. Gene inactivation of valL abolished both
      validoxylamine A and validamycin A productivity, and complementation with a
      cloned valL recovered 10% production of the wild-type in the mutant, indicating
      the involvement of ValL in validoxylamine A biosynthesis. Also we determined the
      structures of ValL and ValL/trehalose complex. The structural data indicates that
      ValL adopts the typical fold of GT-B protein family, featuring two Rossmann-fold
      domains and an active site at domain junction. The residues in the active site
      are arranged in a manner homologous to that of Escherichia coli (E.coli) T6P
      synthase OtsA. However, a significant discrepancy is found in the active-site
      loop region. Also noticeable structural variance is found around the active site
      entrance in the apo ValL structure while the region takes an ordered
      configuration upon binding of product analog trehalose. Furthermore, the modeling
      of V7P in the active site of ValL suggests that ValL might have a similar SNi
      like mechanism as OtsA.

PMID- 22384131
TI  - Global gene expression and systems biology analysis of bovine monocyte-derived
      macrophages in response to in vitro challenge with Mycobacterium bovis.
AB  - BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a
      major cause of mortality in global cattle populations. Macrophages are among the
      first cell types to encounter M. bovis following exposure and the response
      elicited by these cells is pivotal in determining the outcome of infection. Here,
      a functional genomics approach was undertaken to investigate global gene
      expression profiles in bovine monocyte-derived macrophages (MDM) purified from
      seven age-matched non-related females, in response to in vitro challenge with M.
      bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non
      challenged control and M. bovis-challenged MDM for all animals at intervals of 2
      hours, 6 hours and 24 hours post-challenge and prepared for global gene
      expression analysis using the Affymetrix(r) GeneChip(r) Bovine Genome Array.
      RESULTS: Comparison of M. bovis-challenged MDM gene expression profiles with
      those from the non-challenged MDM controls at each time point identified 3,064
      differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267
      differentially expressed genes detected at the 6 hour and 24 hour time points,
      respectively (adjusted P-value threshold <= 0.05). Notably, the number of
      downregulated genes exceeded the number of upregulated genes in the M. bovis
      challenged MDM across all time points; however, the fold-change in expression for
      the upregulated genes was markedly higher than that for the downregulated genes.
      Systems analysis revealed enrichment for genes involved in: (1) the inflammatory
      response; (2) cell signalling pathways, including Toll-like receptors and
      intracellular pathogen recognition receptors; and (3) apoptosis. CONCLUSIONS: The
      increased number of downregulated genes is consistent with previous studies
      showing that M. bovis infection is associated with the repression of host gene
      expression. The results also support roles for MyD88-independent signalling and
      intracellular PRRs in mediating the host response to M. bovis.

PMID- 22384132
TI  - Early versus delayed decompression for traumatic cervical spinal cord injury:
      results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS).
AB  - BACKGROUND: There is convincing preclinical evidence that early decompression in
      the setting of spinal cord injury (SCI) improves neurologic outcomes. However,
      the effect of early surgical decompression in patients with acute SCI remains
      uncertain. Our objective was to evaluate the relative effectiveness of early (<24
      hours after injury) versus late (>= 24 hours after injury) decompressive surgery
      after traumatic cervical SCI. METHODS: We performed a multicenter, international,
      prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study:
      STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002
      and 2009 at 6 North American centers. The primary outcome was ordinal change in
      ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes
      included assessments of complications rates and mortality. FINDINGS: A total of
      313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early
      surgery, at a mean of 14.2(+/- 5.4) hours, with the remaining 131 having late
      surgery, at a mean of 48.3(+/- 29.3) hours. Of the 222 patients with follow-up
      available at 6 months post injury, 19.8% of patients undergoing early surgery
      showed a >= 2 grade improvement in AIS compared to 8.8% in the late decompression
      group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for
      preoperative neurological status and steroid administration, the odds of at least
      a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early
      surgery as compared to those who underwent late surgery (OR = 2.83, 95%
      CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in
      both of the surgical groups. Complications occurred in 24.2% of early surgery
      patients and 30.5% of late surgery patients (p = 0.21). CONCLUSION: Decompression
      prior to 24 hours after SCI can be performed safely and is associated with
      improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6
      months follow-up.

PMID- 22384133
TI  - Grape-derived polyphenols improve aging-related endothelial dysfunction in rat
      mesenteric artery: role of oxidative stress and the angiotensin system.
AB  - Aging is characterized by the development of an endothelial dysfunction, which
      affects both the nitric oxide (NO)- and the endothelium-derived hyperpolarizing
      factor (EDHF)-mediated relaxations, associated with vascular oxidative stress and
      the activation of the angiotensin system. This study investigated whether red
      wine polyphenols (RWPs), antioxidants and potent stimulators of NO- and EDHF
      mediated relaxations improve aging-related endothelial dysfunction, and, if so,
      examined the underlying mechanism. Mesenteric artery reactivity was determined in
      organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX
      staining, and expression of target proteins by immunohistochemical staining.
      Control young rats (16 weeks) received solvent (ethanol, 3% v/v), and middle-aged
      rats (46 weeks) either solvent or RWPs (100 mg/kg/day) in the drinking water. The
      acetylcholine-induced endothelium-dependent NO component was slightly reduced
      whereas the EDHF component was markedly blunted in rings of middle-aged rats
      compared to young rats. The endothelial dysfunction was associated with oxidative
      stress, an upregulation of angiotensin II and AT1 receptors and a down-regulation
      of SK(Ca), IK(Ca), and angiotensin converting enzyme. Intake of RWPs for either
      one or two weeks improved the NO and the EDHF components of the relaxation, and
      normalized oxidative stress, the expression of SK(Ca), IK(Ca) and the components
      of the angiotensin system. The protective effect of the 2-week RWPs treatment
      persisted for one and two weeks following stopping intake of RWPs. Thus, intake
      of RWPs caused a persistent improvement of the endothelial function, particularly
      the EDHF component, in middle-aged rats and this effect seems to involve the
      normalization of the expression of SK(Ca), IK(Ca) and the angiotensin system.

PMID- 22384134
TI  - Roles of MAPK and spindle assembly checkpoint in spontaneous activation and MIII
      arrest of rat oocytes.
AB  - Rat oocytes are well known to undergo spontaneous activation (SA) after leaving
      the oviduct, but the SA is abortive with oocytes being arrested in metaphase III
      (MIII) instead of forming pronuclei. This study was designed to investigate the
      mechanism causing SA and MIII arrest. Whereas few oocytes collected from SD rats
      at 13 h after hCG injection that showed 100% of mitogen-activated protein kinase
      (MAPK) activities activated spontaneously, all oocytes recovered 19 h post hCG
      with MAPK decreased to below 75% underwent SA during in vitro culture. During SA,
      MAPK first declined to below 45% and then increased again to 80%; the maturation
      promoting factor (MPF) activity fluctuated similarly but always began to change
      ahead of the MAPK activity. In SA oocytes with 75% of MAPK activities,
      microtubules were disturbed with irregularly pulled chromosomes dispersed over
      the spindle and the spindle assembly checkpoint (SAC) was activated. When MAPK
      decreased to 45%, the spindle disintegrated and chromosomes surrounded by
      microtubules were scattered in the ooplasm. SA oocytes entered MIII and formed
      several spindle-like structures by 6 h of culture when the MAPK activity re
      increased to above 80%. While SA oocytes showed one Ca(2+) rise, Sr(2+)-activated
      oocytes showed several. Together, the results suggested that SA stimuli triggered
      SA in rat oocytes by inducing a premature MAPK inactivation, which led to
      disturbance of spindle microtubules. The microtubule disturbance impaired pulling
      of chromosomes to the spindle poles, caused spindle disintegration and activated
      SAC. The increased SAC activity reactivated MPF and thus MAPK, leading to MIII
      arrest.

PMID- 22384135
TI  - A replication study of the association between rheumatoid arthritis and deletion
      of the late cornified envelope genes LCE3B and LCE3C.
AB  - OBJECTIVE: Two recent studies, in a Spanish and a Chinese population, point to an
      association between rheumatoid arthritis (RA) risk and the deletion of the Late
      Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor
      for psoriasis. We aimed to replicate these studies in a large Dutch cohort.
      METHODS: 1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del.
      Association analysis was performed for the complete cohort and after
      stratification for the serologic markers anti-cyclic citrullinated peptide and
      rheumatoid factor. A meta-analysis was performed combining our data with the
      Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases
      and 2438 controls. RESULTS: In the Dutch cohort we did not observe a significant
      association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis
      for the serologic positive and negative group did not show an association between
      the genetic variant and disease risk, either. The meta-analysis, however,
      confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval
      1.16-1.47). CONCLUSION: Our meta-analysis confirms the association of the LCE3
      deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for
      (auto)immune diseases.

PMID- 22384136
TI  - Rapid enzymatic response to compensate UV radiation in copepods.
AB  - Ultraviolet radiation (UVR) causes physical damage to DNA, carboxylation of
      proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and
      abundant secondary producers in most aquatic ecosystems. Copepod adaptations for
      long duration exposures include changes in behaviour, changes in pigmentation and
      ultimately changes in morphology. Adaptations to short-term exposures are little
      studied. Here we show that short-duration exposure to UVR causes the freshwater
      calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes
      that prevent widespread collateral peroxidation (glutathione S-transferase, GST),
      that regulate apoptosis cell death (Caspase-3, Casp-3), and that facilitate
      neurotransmissions (cholinesterase-ChE). None of these enzyme systems is alone
      sufficient, but they act in concert to reduce the stress level of the organism.
      The interplay among enzymatic responses provides useful information on how
      organisms respond to environmental stressors acting on short time scales.

PMID- 22384137
TI  - IKAP/Elp1 is required in vivo for neurogenesis and neuronal survival, but not for
      neural crest migration.
AB  - Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III)
      manifests from a failure in development of the peripheral sensory and autonomic
      nervous systems. The disease results from a point mutation in the IKBKAP gene,
      which encodes the IKAP protein, whose function is still unresolved in the
      developing nervous system. Since the neurons most severely depleted in the
      disease derive from the neural crest, and in light of data identifying a role for
      IKAP in cell motility and migration, it has been suggested that FD results from a
      disruption in neural crest migration. To determine the function of IKAP during
      development of the nervous system, we (1) first determined the spatial-temporal
      pattern of IKAP expression in the developing peripheral nervous system, from the
      onset of neural crest migration through the period of programmed cell death in
      the dorsal root ganglia, and (2) using RNAi, reduced expression of IKBKAP mRNA in
      the neural crest lineage throughout the process of dorsal root ganglia (DRG)
      development in chick embryos in ovo. Here we demonstrate that IKAP is not
      expressed by neural crest cells and instead is expressed as neurons differentiate
      both in the CNS and PNS, thus the devastation of the PNS in FD could not be due
      to disruptions in neural crest motility or migration. In addition, we show that
      alterations in the levels of IKAP, through both gain and loss of function
      studies, perturbs neuronal polarity, neuronal differentiation and survival. Thus
      IKAP plays pleiotropic roles in both the peripheral and central nervous systems.

PMID- 22384138
TI  - Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral
      prophylaxis for prevention of vertical HIV-1 transmission.
AB  - BACKGROUND: WHO-guidelines for prevention of mother-to-child transmission of HIV
      1 in resource-limited settings recommend complex maternal antiretroviral
      prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP
      SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum.
      Data on resistance development selected by this regimen is not available. We
      therefore analyzed the emergence of minor drug-resistant HIV-1 variants in
      Tanzanian women following complex prophylaxis. METHOD: 1395 pregnant women were
      tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women
      started complex prophylaxis. Blood samples were collected before start of
      prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific
      real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and
      applied on samples of mothers and their vertically infected infants to quantify
      key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC
      (M184V) at detection limits of <1%. RESULTS: 50/87 HIV-infected women having
      started complex prophylaxis were eligible for the study. All women took AZT with
      a median duration of 53 days (IQR 39-64); all women ingested NVP-SD, 86% took
      3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70%
      displayed minority species. Variants with AZT-resistance mutations were found in
      11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in
      4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug.
      49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7
      infants exhibited drug-resistant virus. CONCLUSION: Complex prophylaxis resulted
      in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT
      resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in
      pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may
      further increase the frequency of AZT-resistance mutations. Given its impact on
      HIV-transmission rate and drug-resistance development, HAART for all HIV-positive
      pregnant women should be considered.

PMID- 22384139
TI  - Incidence of respiratory virus-associated pneumonia in urban poor young children
      of Dhaka, Bangladesh, 2009-2011.
AB  - BACKGROUND: Pneumonia is the leading cause of childhood death in Bangladesh. We
      conducted a longitudinal study to estimate the incidence of virus-associated
      pneumonia in children aged <2 years in a low-income urban community in Dhaka,
      Bangladesh. METHODS: We followed a cohort of children for two years. We collected
      nasal washes when children presented with respiratory symptoms. Study physicians
      diagnosed children with cough and age-specific tachypnea and positive lung
      findings as pneumonia case-patients. We tested respiratory samples for
      respiratory syncytial virus (RSV), rhinoviruses, human metapneumovirus (HMPV),
      influenza viruses, human parainfluenza viruses (HPIV 1, 2, 3), and adenoviruses
      using real-time reverse transcription polymerase chain reaction assays. RESULTS:
      Between April 2009-March 2011, we followed 515 children for 730 child-years. We
      identified a total of 378 pneumonia episodes, 77% of the episodes were associated
      with a respiratory viral pathogen. The overall incidence of pneumonia associated
      with a respiratory virus infection was 40/100 child-years. The annual incidence
      of pneumonia/100 child-years associated with a specific respiratory virus in
      children aged < 2 years was 12.5 for RSV, 6 for rhinoviruses, 6 for HMPV, 4 for
      influenza viruses, 3 for HPIV and 2 for adenoviruses. CONCLUSION: Young children
      in Dhaka are at high risk of childhood pneumonia and the majority of these
      episodes are associated with viral pathogens. Developing effective low-cost
      strategies for prevention are a high priority.

PMID- 22384140
TI  - Cellular autofluorescence following ionizing radiation.
AB  - Cells often autofluoresce in response to UV radiation excitation and this can
      reflect critical aspects of cellular metabolism. Here we report that many
      different human and murine cell types respond to ionizing radiation with a
      striking rise in autofluorescence that is dependent on dose and time. There was a
      highly reproducible fluorescent shift at various wavelengths, which was mirrored
      by an equally reproducible rise in the vital intracellular metabolic co-factors
      FAD and NADH. It appears that mitochondria, metabolism and Ca(2+) homeostasis are
      important for this to occur as cells without mitochondria or cells unable to
      alter calcium levels did not behave in this way. We believe these radiation
      induced changes are of biological importance and that autofluorescence may even
      provide us with a tool to monitor radiation responses in the clinic.

PMID- 22384141
TI  - MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant
      transformation from benign tumors.
AB  - BACKGROUND: MicroRNA (miRNA) expression profiles have been described in
      pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with
      pre-malignant pancreatic tumors. We wished to compare the miRNA expression
      signatures in pancreatic benign cystic tumors (BCT) of low and high malignant
      potential with PDAC, in order to identify miRNAs deregulated during PDAC
      development. The mechanistic consequences of miRNA dysregulation were further
      evaluated. METHODS: Tissue samples were obtained at a tertiary pancreatic unit
      from individuals with BCT and PDAC. MiRNA profiling was performed using a custom
      microarray and results were validated using RT-qPCR prior to evaluation of miRNA
      targets. RESULTS: Widespread miRNA down-regulation was observed in PDAC compared
      to low malignant potential BCT. We show that amongst those miRNAs down-regulated,
      miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and
      KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at
      a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was
      strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and
      CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and
      other cancers, was not elevated in PDAC compared to serous microcystic adenoma
      (SMCA), but in both groups it was up-regulated compared to normal pancreas,
      implicating early up-regulation during malignant change. CONCLUSIONS: Expression
      profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most
      benign lesion that rarely progresses to invasive carcinoma. It appears that miR
      21 up-regulation is an early event in the transformation from normal pancreatic
      tissue. MiRNA expression has the potential to distinguish PDAC from normal
      pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let
      7d promotes PDAC transformation by post-transcriptional up-regulation of crucial
      PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re
      expression has the potential as a therapeutic strategy against PDAC and other
      KRAS-driven cancers.

PMID- 22384142
TI  - Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal
      dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs.
AB  - In humans, congenital and hereditary skin diseases associated with epidermal cell
      cell separation (acantholysis) are very rare, and spontaneous animal models of
      these diseases are exceptional. Our objectives are to report a novel congenital
      acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine
      affected puppies in four different litters were born to eight closely related
      clinically normal dogs. The disease transmission was consistent with an autosomal
      recessive mode of inheritance. Clinical signs occurred immediately after birth
      with superficial epidermal layers sloughing upon pressure. At three month of age,
      dogs exhibited recurrent superficial skin sloughing and erosions at areas of
      friction and mucocutaneous junctions; their coat was also finer than normal and
      there were patches of partial hair loss. At birth, histopathology revealed severe
      suprabasal acantholysis, which became less severe with ageing. Electron
      microscopy demonstrated a reduced number of partially formed desmosomes with
      detached and aggregated keratin intermediate filaments. Immunostaining for
      desmosomal adhesion molecules revealed a complete lack of staining for
      plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10
      and 14. Sequencing revealed a homozygous splice donor site mutation within the
      first intron of PKP1 resulting in a premature stop codon, thereby explaining the
      inability to detect plakophilin-1 in the skin. Altogether, the clinical and
      pathological findings, along with the PKP1 mutation, were consistent with the
      diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1
      deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility
      syndrome in an animal species. Controlled mating of carrier dogs would yield
      puppies that could, in theory, be tested for gene therapy of this rare but severe
      skin disease of children.

PMID- 22384143
TI  - Organizational heterogeneity of vertebrate genomes.
AB  - Genomes of higher eukaryotes are mosaics of segments with various structural,
      functional, and evolutionary properties. The availability of whole-genome
      sequences allows the investigation of their structure as "texts" using different
      statistical and computational methods. One such method, referred to as
      Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed
      length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows
      generating species- or region-specific characteristics of the genome, regardless
      of their length and the presence of coding DNA. In this study, we consider the
      heterogeneity of vertebrate genomes as a joint effect of regional variation in
      sequence organization superimposed on the differences in nucleotide composition.
      We estimated compositional and organizational heterogeneity of genome and
      chromosome sequences separately and found that both heterogeneity types vary
      widely among genomes as well as among chromosomes in all investigated taxonomic
      groups. The high correspondence of heterogeneity scores obtained on three genome
      fractions, coding, repetitive, and the remaining part of the noncoding DNA (the
      genome dark matter--GDM) allows the assumption that CS-heterogeneity may have
      functional relevance to genome regulation. Of special interest for such
      interpretation is the fact that natural GDM sequences display the highest
      deviation from the corresponding reshuffled sequences.

PMID- 22384144
TI  - G Protein betagamma-subunit signaling mediates airway hyperresponsiveness and
      inflammation in allergic asthma.
AB  - Since the Gbetagamma subunit of Gi protein has been importantly implicated in
      regulating immune and inflammatory responses, this study investigated the
      potential role and mechanism of action of Gbetagamma signaling in regulating the
      induction of airway hyperresponsiveness (AHR) in a rabbit model of allergic
      asthma. Relative to non-sensitized animals, OVA-sensitized rabbits challenged
      with inhaled OVA exhibited AHR, lung inflammation, elevated BAL levels of IL-13,
      and increased airway phosphodiesterase-4 (PDE4) activity. These proasthmatic
      responses were suppressed by pretreatment with an inhaled membrane-permeable anti
      Gbetagamma blocking peptide, similar to the suppressive effect of glucocorticoid
      pretreatment. Extended mechanistic studies demonstrated that: 1) corresponding
      proasthmatic changes in contractility exhibited in isolated airway smooth muscle
      (ASM) sensitized with serum from OVA-sensitized+challenged rabbits or IL-13 were
      also Gbetagamma-dependent and mediated by MAPK-upregulated PDE4 activity; and 2)
      the latter was attributed to Gbetagamma-induced direct stimulation of the non
      receptor tyrosine kinase, c-Src, resulting in downstream activation of ERK1/2 and
      its consequent transcriptional upregulation of PDE4. Collectively, these data are
      the first to identify that a mechanism involving Gbetagamma-induced direct
      activation of c-Src, leading to ERK1/2-mediated upregulation of PDE4 activity,
      plays a decisive role in regulating the induction of AHR and inflammation in a
      rabbit model of allergic airway disease.

PMID- 22384145
TI  - Receptor-specific mechanisms regulate phosphorylation of AKT at Ser473: role of
      RICTOR in beta1 integrin-mediated cell survival.
AB  - A tight control over AKT/PKB activation is essential for cells, and they realise
      this in part by regulating the phosphorylation of Ser473 in the "hydrophobic
      motif" of the AKT carboxy-terminal region. The RICTOR-mTOR complex (TORC2) is a
      major kinase for AKT Ser473 phosphorylation after stimulation by several growth
      factors, in a reaction proposed to require p21-activated kinase (PAK) as a
      scaffold. However, other kinases may catalyse this reaction in stimuli-specific
      manners. Here we characterised the requirement of RICTOR, ILK, and PAK for AKT
      Ser473 phosphorylation downstream of selected family members of integrins, G
      protein-coupled receptors, and tyrosine-kinase receptors and analysed the
      importance of this phosphorylation site for adhesion-mediated survival. siRNA
      mediated knockdown in HeLa and MCF7 cells showed that RICTOR-mTOR was required
      for phosphorylation of AKT Ser473, and for efficient phosphorylation of the
      downstream AKT targets FOXO1 Thr24 and BAD Ser136, in response to beta1 integrin
      stimulation. ILK and PAK1/2 were dispensable for these reactions. RICTOR
      knockdown increased the number of apoptotic MCF7 cells on beta1 integrin ligands
      up to 2-fold after 24 h in serum-free conditions. beta1 integrin-stimulation
      induced phosphorylation of both AKT1 and AKT2 but markedly preferred AKT2. RICTOR
      mTOR was required also for LPA-induced AKT Ser473 phosphorylation in MCF7 cells,
      but, interestingly, not in HeLa cells. PAK was needed for the AKT Ser473
      phosphorylation in response to LPA and PDGF, but not to EGF. These results
      demonstrate that different receptors utilise different enzyme complexes to
      phosphorylate AKT at Ser473, and that AKT Ser473 phosphorylation significantly
      contributes to beta1 integrin-mediated anchorage-dependent survival of cells.

PMID- 22384147
TI  - Considerations for assessing maximum critical temperatures in small ectothermic
      animals: insights from leaf-cutting ants.
AB  - The thermal limits of individual animals were originally proposed as a link
      between animal physiology and thermal ecology. Although this link is valid in
      theory, the evaluation of physiological tolerances involves some problems that
      are the focus of this study. One rationale was that heating rates shall influence
      upper critical limits, so that ecological thermal limits need to consider
      experimental heating rates. In addition, if thermal limits are not surpassed in
      experiments, subsequent tests of the same individual should yield similar results
      or produce evidence of hardening. Finally, several non-controlled variables such
      as time under experimental conditions and procedures may affect results. To
      analyze these issues we conducted an integrative study of upper critical
      temperatures in a single species, the ant Atta sexdens rubropiosa, an animal
      model providing large numbers of individuals of diverse sizes but similar genetic
      makeup. Our specific aims were to test the 1) influence of heating rates in the
      experimental evaluation of upper critical temperature, 2) assumptions of absence
      of physical damage and reproducibility, and 3) sources of variance often
      overlooked in the thermal-limits literature; and 4) to introduce some
      experimental approaches that may help researchers to separate physiological and
      methodological issues. The upper thermal limits were influenced by both heating
      rates and body mass. In the latter case, the effect was physiological rather than
      methodological. The critical temperature decreased during subsequent tests
      performed on the same individual ants, even one week after the initial test.
      Accordingly, upper thermal limits may have been overestimated by our (and
      typical) protocols. Heating rates, body mass, procedures independent of
      temperature and other variables may affect the estimation of upper critical
      temperatures. Therefore, based on our data, we offer suggestions to enhance the
      quality of measurements, and offer recommendations to authors aiming to compile
      and analyze databases from the literature.

PMID- 22384146
TI  - Scopolamine administration modulates muscarinic, nicotinic and NMDA receptor
      systems.
AB  - Studies on the effect of scopolamine on memory are abundant but so far only
      regulation of the muscarinic receptor (M1) has been reported. We hypothesized
      that levels of other cholinergic brain receptors as the nicotinic receptors and
      the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory
      formation, would be modified by scopolamine administration.C57BL/6J mice were
      used for the experiments and divided into four groups. Two groups were given
      scopolamine 1 mg/kg i.p. (the first group was trained and the second group
      untrained) in the multiple T-maze (MTM), a paradigm for evaluation of spatial
      memory. Likewise, vehicle-treated mice were trained or untrained thus serving as
      controls. Hippocampal levels of M1, nicotinic receptor alpha 4 (Nic4) and 7
      (Nic7) and subunit NR1containing complexes were determined by immunoblotting on
      blue native gel electrophoresis.Vehicle-treated trained mice learned the task and
      showed memory retrieval on day 8, while scopolamine-treatment led to significant
      impairment of performance in the MTM. At the day of retrieval, hippocampal levels
      for M1, Nic7 and NR1 were higher in the scopolamine treated groups than in
      vehicle-treated groups.The concerted action, i.e. the pattern of four brain
      receptor complexes regulated by the anticholinergic compound scopolamine, is
      shown. Insight into probable action mechanisms of scopolamine at the brain
      receptor complex level in the hippocampus is provided. Scopolamine treatment is a
      standard approach to test cognitive enhancers and other psychoactive compounds in
      pharmacological studies and therefore knowledge on mechanisms is of pivotal
      interest.

PMID- 22384148
TI  - Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal
      differentiation induced by NGF.
AB  - The Sprouty (Spry) family of proteins represents endogenous regulators of
      downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using
      real time PCR, we detect a significant increase in the expression of Spry4 mRNA
      in response to NGF, indicating that Spry4 could modulate intracellular signaling
      pathways and biological processes induced by NGF and its receptor TrkA. In this
      work, we demonstrate that overexpression of wild-type Spry4 causes a significant
      reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At
      molecular level, our findings indicate that ectopic expression of a mutated form
      of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to
      block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by
      NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory
      effect of Spry4 on NGF signaling. Downregulation of Spry4 using small
      interference RNA knockdown experiments potentiates PC12 cell differentiation and
      MAPK activation in response to NGF. Together, these findings establish a new
      physiological mechanism through which Spry4 regulates neurite outgrowth reducing
      not only the MAPK pathway but also restricting Rac1 activation in response to
      NGF.

PMID- 22384149
TI  - A survey of genomic studies supports association of circadian clock genes with
      bipolar disorder spectrum illnesses and lithium response.
AB  - Circadian rhythm abnormalities in bipolar disorder (BD) have led to a search for
      genetic abnormalities in circadian "clock genes" associated with BD. However, no
      significant clock gene findings have emerged from genome-wide association studies
      (GWAS). At least three factors could account for this discrepancy: complex traits
      are polygenic, the organization of the clock is more complex than previously
      recognized, and/or genetic risk for BD may be shared across multiple illnesses.
      To investigate these issues, we considered the clock gene network at three
      levels: essential "core" clock genes, upstream circadian clock modulators, and
      downstream clock controlled genes. Using relaxed thresholds for GWAS statistical
      significance, we determined the rates of clock vs. control genetic associations
      with BD, and four additional illnesses that share clinical features and/or
      genetic risk with BD (major depression, schizophrenia, attention
      deficit/hyperactivity). Then we compared the results to a set of lithium
      responsive genes. Associations with BD-spectrum illnesses and lithium
      responsiveness were both enriched among core clock genes but not among upstream
      clock modulators. Associations with BD-spectrum illnesses and lithium
      responsiveness were also enriched among pervasively rhythmic clock-controlled
      genes but not among genes that were less pervasively rhythmic or non-rhythmic.
      Our analysis reveals previously unrecognized associations between clock genes and
      BD-spectrum illnesses, partly reconciling previously discordant results from past
      GWAS and candidate gene studies.

PMID- 22384150
TI  - Genetic architecture of local adaptation in lunar and diurnal emergence times of
      the marine midge Clunio marinus (Chironomidae, Diptera).
AB  - Circadian rhythms pre-adapt the physiology of most organisms to predictable daily
      changes in the environment. Some marine organisms also show endogenous circalunar
      rhythms. The genetic basis of the circalunar clock and its interaction with the
      circadian clock is unknown. Both clocks can be studied in the marine midge Clunio
      marinus (Chironomidae, Diptera), as different populations have different local
      adaptations in their lunar and diurnal rhythms of adult emergence, which can be
      analyzed by crossing experiments. We investigated the genetic basis of population
      variation in clock properties by constructing the first genetic linkage map for
      this species, and performing quantitative trait locus (QTL) analysis on variation
      in both lunar and diurnal timing. The genome has a genetic length of 167-193
      centimorgans based on a linkage map using 344 markers, and a physical size of 95
      140 megabases estimated by flow cytometry. Mapping the sex determining locus
      shows that females are the heterogametic sex, unlike most other Chironomidae. We
      identified two QTL each for lunar emergence time and diurnal emergence time. The
      distribution of QTL confirms a previously hypothesized genetic basis to a
      correlation of lunar and diurnal emergence times in natural populations. Mapping
      of clock genes and light receptors identified ciliary opsin 2 (cOps2) as a
      candidate to be involved in both lunar and diurnal timing; cryptochrome 1 (cry1)
      as a candidate gene for lunar timing; and two timeless (tim2, tim3) genes as
      candidate genes for diurnal timing. This QTL analysis of lunar rhythmicity, the
      first in any species, provides a unique entree into the molecular analysis of the
      lunar clock.

PMID- 22384151
TI  - Identification of cancer cell-line origins using fluorescence image-based
      phenomic screening.
AB  - Universal phenotyping techniques that can discriminate among various states of
      biological systems have great potential. We applied 557 fluorescent library
      compounds to NCI's 60 human cancer cell-lines (NCI-60) to generate a systematic
      fluorescence phenotypic profiling data. By the kinetic fluorescence intensity
      analysis, we successfully discriminated the organ origin of all the 60 cell
      lines.

PMID- 22384152
TI  - Interaction between M-like protein and macrophage thioredoxin facilitates
      antiphagocytosis for Streptococcus equi ssp. zooepidemicus.
AB  - Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, S.z) is one of the
      common pathogens that can cause septicemia, meningitis, and mammitis in
      domesticated species. M-like protein (SzP) is an important virulence factor of S.
      zooepidemicus and contributes to bacterial infection and antiphagocytosis. The
      interaction between SzP of S. zooepidemicus and porcine thioredoxin (TRX) was
      identified by the yeast two-hybrid and further confirmed by co
      immunoprecipitation. SzP interacted with both reduced and the oxidized forms of
      TRX without inhibiting TRX activity. Membrane anchored SzP was able to recruit
      TRX to the surface, which would facilitate the antiphagocytosis of the bacteria.
      Further experiments revealed that TRX regulated the alternative complement
      pathway by inhibiting C3 convertase activity and associating with factor H (FH).
      TRX alone inhibited C3 cleavage and C3a production, and the inhibitory effect was
      additive when FH was also present. TRX inhibited C3 deposition on the bacterial
      surface when it was recruited by SzP. These new findings indicated that S.
      zooepidemicus used SzP to recruit TRX and regulated the alternative complement
      pathways to evade the host immune phagocytosis.

PMID- 22384153
TI  - Multidrug-resistant and extensively drug-resistant tuberculosis in multi-ethnic
      region, Xinjiang Uygur Autonomous Region, China.
AB  - BACKGROUND: The multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic
      region and suffered second highest incidence of TB in China. However,
      epidemiological information on MDR and XDR TB is scarcely investigated.
      METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was conducted to analyze the
      prevalence of MDR and XDR TB and the differences of drug resistance TB between
      Chinese Han and other nationalities population at Chest Hospital of Xinjiang
      Uygur Autonomous Region, China. We performed in vitro drug susceptibility testing
      of Mycobacterium tuberculosis to first- and second-line anti-tuberculosis drugs
      for all 1893 culture confirmed positive TB cases that were diagnosed between June
      2009 and June 2011. Totally 1117 (59.0%, 95% CI, 56.8%-61.2%) clinical isolates
      were resistant to >=1 first-line drugs; the prevalence of MDR TB was 13.2% (95%
      CI, 11.7%-14.7%), of which, 77 (30.8%; 95% CI, 25.0%-36.6%) and 31 (12.8%; 95%
      CI, 8.6%-17.0%) isolates were pre-XDR and XDR TB respectively. Among the MDR/XDR
      TB, Chinese Han patients were significantly less likely to be younger with an
      odds ratio 0.42 for age 20-29 years and 0.52 for age 40-49 years; P(trend) =
      0.004), and Chinese Han patients has a lower prevalence of XDR TB (9.6%) than all
      the other nationality (14.9%). CONCLUSIONS/SIGNIFICANCE: The burden of drug
      resistance TB cases is sizeable, which highlights an urgent need to reinforce the
      control, detection and treatment strategies for drug resistance TB. However, the
      difference of MDR and XDR TB between Chinese Han and other nationalities was not
      observed.

PMID- 22384154
TI  - Helicobacter pylori seropositivity and risk of lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter
      pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small
      studies have suggested that H. pylori may be a potential risk factor for lung
      cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma
      cases, 350 squamous cell carcinoma cases, and 700 controls nested within the
      Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male
      Finnish smokers. Controls were one-to-one matched by age and date of baseline
      serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G
      antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA)
      antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs)
      for associations between H. pylori seropositivity and lung cancer risk using
      conditional logistic regression. H. pylori seropositivity was detected in 79.7%
      of cases and 78.5% of controls. After adjusting for pack-years and cigarettes
      smoked per day, H. pylori seropositivity was not associated with either
      adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1,
      95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H.
      pylori seropositivity. Despite earlier small studies suggesting that H. pylori
      may contribute to lung carcinogenesis, H. pylori seropositivity does not appear
      to be associated with lung cancer.

PMID- 22384155
TI  - Benign orbital tumors with bone destruction in children.
AB  - PURPOSE: To present rare benign orbital tumors with bone destruction in children
      who could not be diagnosed pre-surgically and may simulate malignant ones.
      METHODS: A retrospective review of cases. Clinical, operative and pathological
      records in all children with a diagnosis of benign orbital tumors who showed
      remarkable bone destruction at a tertiary Ophthalmic Center in China between Jan
      1, 2000 and Dec 31, 2009 were reviewed. All patients had definitive
      histopathologic diagnosis. RESULTS: Eight patients with benign orbital tumors
      showed obvious bone destruction, including six cases of eosinophilic granuloma,
      one case of leiomyoma and one case of primary orbital intraosseous hemangioma.
      Among them, three patients were females and five patients were males. Tumors were
      unilateral in all cases, with both the right and left side affected equally. Age
      ranged from 3 to 7 years (mean 4.1 years). Symptom duration ranged from 1 to 5
      weeks (mean 4.8 weeks). Eyelid swelling and palpable mass were the most common
      complaint. There was no evidence for multifocal involvement in cases with
      eosinophilic granuloma. Among six patients with eosinophilic granuloma, two were
      treated with low dose radiation (10 Gy), three received systemic corticosteroid
      and one was periodically observed only after incisional biopsy or subtotal
      curettage. There was no postoperative therapeutic intervention in the two
      patients with leiomyoma and intraosseous hemangioma. All eight patients regained
      normal vision without local recurrence after a mean follow-up time of 32.8
      months. CONCLUSION: Benign orbital tumors such as isolated eosinophilic
      granuloma, leiomyoma and primary orbital intraosseous hemangioma may show
      remarkable bone destruction.

PMID- 22384156
TI  - Addressing cancer disparities via community network mobilization and
      intersectoral partnerships: a social network analysis.
AB  - Community mobilization and collaboration among diverse partners are vital
      components of the effort to reduce and eliminate cancer disparities in the United
      States. We studied the development and impact of intersectoral connections among
      the members of the Massachusetts Community Network for Cancer Education,
      Research, and Training (MassCONECT). As one of the Community Network Program
      sites funded by the National Cancer Institute, this infrastructure-building
      initiative utilized principles of Community-based Participatory Research (CBPR)
      to unite community coalitions, researchers, policymakers, and other important
      stakeholders to address cancer disparities in three Massachusetts communities:
      Boston, Lawrence, and Worcester. We conducted a cross-sectional, sociometric
      network analysis four years after the network was formed. A total of 38 of 55
      members participated in the study (69% response rate). Over four years of
      collaboration, the number of intersectoral connections reported by members
      (intersectoral out-degree) increased, as did the extent to which such connections
      were reported reciprocally (intersectoral reciprocity). We assessed relationships
      between these markers of intersectoral collaboration and three intermediate
      outcomes in the effort to reduce and eliminate cancer disparities: delivery of
      community activities, policy engagement, and grants/publications. We found a
      positive and statistically significant relationship between intersectoral out
      degree and community activities and policy engagement (the relationship was
      borderline significant for grants/publications). We found a positive and
      statistically significant relationship between intersectoral reciprocity and
      community activities and grants/publications (the relationship was borderline
      significant for policy engagement). The study suggests that intersectoral
      connections may be important drivers of diverse intermediate outcomes in the
      effort to reduce and eliminate cancer disparities. The findings support
      investment in infrastructure-building and intersectoral mobilization in
      addressing disparities and highlight the benefits of using CBPR approaches for
      such work.

PMID- 22384157
TI  - Systematic validation of protein force fields against experimental data.
AB  - Molecular dynamics simulations provide a vehicle for capturing the structures,
      motions, and interactions of biological macromolecules in full atomic detail. The
      accuracy of such simulations, however, is critically dependent on the force field
      -the mathematical model used to approximate the atomic-level forces acting on the
      simulated molecular system. Here we present a systematic and extensive evaluation
      of eight different protein force fields based on comparisons of experimental data
      with molecular dynamics simulations that reach a previously inaccessible
      timescale. First, through extensive comparisons with experimental NMR data, we
      examined the force fields' abilities to describe the structure and fluctuations
      of folded proteins. Second, we quantified potential biases towards different
      secondary structure types by comparing experimental and simulation data for small
      peptides that preferentially populate either helical or sheet-like structures.
      Third, we tested the force fields' abilities to fold two small proteins--one
      alpha-helical, the other with beta-sheet structure. The results suggest that
      force fields have improved over time, and that the most recent versions, while
      not perfect, provide an accurate description of many structural and dynamical
      properties of proteins.

PMID- 22384158
TI  - Human platelet-rich plasma- and extracellular matrix-derived peptides promote
      impaired cutaneous wound healing in vivo.
AB  - Previous work in our laboratory has described several pro-angiogenic short
      peptides derived from endothelial extracellular matrices degraded by bacterial
      collagenase. Here we tested whether these peptides could stimulate wound healing
      in vivo. Our experiments demonstrated that a peptide created as combination of
      fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal
      wounds created in mice treated with cyclophosphamide to impair wound healing, can
      improve the rate of wound closure. Furthermore, we identify and characterize a
      novel peptide (UN3) created and modified from two naturally-occurring peptides,
      which are present in human platelet-rich plasma. In vitro testing of UN3
      demonstrates that it causes a 50% increase in endothelial proliferation, 250%
      increase in angiogenic response and a tripling of epithelial cell migration in
      response to injury. Results of in vivo experiments where comb1 and UN3 peptides
      were added together to cranial wounds in cyclophosphamide-treated mice leads to
      improvement of wound vascularization as shown by an increase of the number of
      blood vessels present in the wound beds. Application of the peptides markedly
      promotes cellular responses to injury and essentially restores wound healing
      dynamics to those of normal, acute wounds in the absence of cyclophosphamide
      impairment. Our current work is aimed at understanding the mechanisms underlying
      the stimulatory effects of these peptides as well as identification of the
      cellular receptors mediating these effects.

PMID- 22384159
TI  - Molecular targets for 17alpha-ethynyl-5-androstene-3beta,7beta,17beta-triol, an
      anti-inflammatory agent derived from the human metabolome.
AB  - HE3286, 17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol, is a novel
      synthetic compound related to the endogenous sterol 5-androstene-3beta, 7beta,
      17beta-triol (beta-AET), a metabolite of the abundant adrenal steroid
      dehydroepiandrosterone (DHEA). HE3286 has shown efficacy in clinical studies in
      impaired glucose tolerance and type 2 diabetes, and in vivo models of types 1 and
      2 diabetes, autoimmunity, and inflammation. Proteomic analysis of solid-phase
      HE3286-bound bead affinity experiments, using extracts from RAW 264.7 mouse
      macrophage cells, identified 26 binding partners. Network analysis revealed
      associations of these HE3286 target proteins with nodes in the Kyoto Encyclopedia
      of Genes and Genomes (KEGG) pathways for type 2 diabetes, insulin, adipokine, and
      adipocyte signaling. Binding partners included low density lipoprotein receptor
      related protein (Lrp1), an endocytic receptor; mitogen activated protein kinases
      1 and 3 (Mapk1, Mapk3), protein kinases involved in inflammation signaling
      pathways; ribosomal protein S6 kinase alpha-3 (Rsp6ka3), an intracellular
      regulatory protein; sirtuin-2 (Sirt2); and 17beta-hydroxysteroid dehydrogenase 1
      (Hsd17beta4), a sterol metabolizing enzyme.

PMID- 22384160
TI  - Epidemiologic characterization of human papillomavirus infection in rural
      Chaozhou, eastern Guangdong Province of China.
AB  - BACKGROUND: Human papilloma virus (HPV) infection was the main cause of cervical
      cancer. There were only a few reports and detailed data about epidemiological
      research of HPV infection in rural population of China. MATERIALS AND METHODS:
      The cervical cells of rural Chaozhou women were collected, and multiplex real
      time PCR was firstly performed to detect high-risk HPV (HR-HPV) infection, which
      could detect 13 types of HR-HPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56,
      58, 59, and 68). Then, HPV-positive samples were typed by HPV GenoArray test.
      RESULTS: HR-HPV DNA was detected by multiplex real time-PCR in 3830 of 48559
      cases (7.89%). There was a peak incidence in age of 55-60 years group, and a
      lower incidence in who lived in plain group compared with suburban, mountain and
      seashore group. 3380 cases of HPV positive sample were genotyped, 11.01%
      (372/3380) cases could not be classified, among the typed 3008 cases, 101 cases
      were identified without HR-HPV type infection, 2907 cases were infected with one
      HR-HPV type at least, the 6 most common HR-HPV types in descending order of
      infection, were type 52 (33.4%, 16 (20.95%), 58 (15.93%), 33 (9.94%), 68 (9.22%)
      and 18 (8.36%). The combined prevalence of HPV types 16 and 18 accounted for
      28.52% of total infection. However, type 52 plus 58 presented 48.23% of total
      infection. 2209/2907 cases were infected with a single HPV type and 698/2907
      cases were infected with multiple types, and multiple infection constituent ratio
      increased with age, with a peak incidence in age 55-60 years group. CONCLUSIONS:
      Our findings showed low prevalence of HPV vaccine types (16 and 18) and
      relatively high prevalence of HPV-52 and -58, support the hypothesis that the
      second-generation HPV vaccines including HPV-52 and -58 may offer higher
      protection for women in rural Guangdong Province.

PMID- 22384161
TI  - Identification of candidate susceptibility and resistance genes of mice infected
      with Streptococcus suis type 2.
AB  - Streptococcus suis type 2 (SS2) is an important swine pathogen and zoonosis
      agent. A/J mice are significantly more susceptible than C57BL/6 (B6) mice to SS2
      infection, but the genetic basis is largely unknown. Here, alterations in gene
      expression in SS2 (strain HA9801)-infected mice were identified using Illumina
      mouse BeadChips. Microarray analysis revealed 3,692 genes differentially
      expressed in peritoneal macrophages between A/J and B6 mice due to SS2 infection.
      Between SS2-infected A/J and control A/J mice, 2646 genes were differentially
      expressed (1469 upregulated; 1177 downregulated). Between SS2-infected B6 and
      control B6 mice, 1449 genes were differentially expressed (778 upregulated; 671
      downregulated). These genes were analyzed for significant Gene Ontology (GO)
      categories and signaling pathways using the Kyoto Encylopedia of Genes and
      Genomes (KEGG) database to generate a signaling network. Upregulated genes in A/J
      and B6 mice were related to response to bacteria, immune response, positive
      regulation of B cell receptor signaling pathway, type I interferon biosynthesis,
      defense and inflammatory responses. Additionally, upregulated genes in SS2
      infected B6 mice were involved in antigen processing and presentation of
      exogenous peptides, peptide antigen stabilization, lymphocyte differentiation
      regulation, positive regulation of monocyte differentiation, antigen receptor
      mediated signaling pathway and positive regulation of phagocytosis. Downregulated
      genes in SS2-infected B6 mice played roles in glycolysis, carbohydrate metabolic
      process, amino acid metabolism, behavior and muscle regulation. Microarray
      results were verified by quantitative real-time PCR (qRT-PCR) of 14
      representative deregulated genes. Four genes differentially expressed between SS2
      infected A/J and B6 mice, toll-like receptor 2 (Tlr2), tumor necrosis factor
      (Tnf), matrix metalloproteinase 9 (Mmp9) and pentraxin 3 (Ptx3), were previously
      implicated in the response to S. suis infection. This study identified candidate
      genes that may influence susceptibility or resistance to SS2 infection in A/J and
      B6 mice, providing further validation of these models and contributing to
      understanding of S. suis pathogenic mechanisms.

PMID- 22384163
TI  - Higher level phylogeny and the first divergence time estimation of Heteroptera
      (Insecta: Hemiptera) based on multiple genes.
AB  - Heteroptera, or true bugs, are the largest, morphologically diverse and
      economically important group of insects with incomplete metamorphosis. However,
      the phylogenetic relationships within Heteroptera are still in dispute and most
      of the previous studies were based on morphological characters or with single
      gene (partial or whole 18S rDNA). Besides, so far, divergence time estimates for
      Heteroptera totally rely on the fossil record, while no studies have been
      performed on molecular divergence rates. Here, for the first time, we used
      maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) with
      multiple genes (18S rDNA, 28S rDNA, 16S rDNA and COI) to estimate phylogenetic
      relationships among the infraorders, and meanwhile, the Penalized Likelihood
      (r8s) and Bayesian (BEAST) molecular dating methods were employed to estimate
      divergence time of higher taxa of this suborder. Major results of the present
      study included: Nepomorpha was placed as the most basal clade in all six trees
      (MP trees, ML trees and Bayesian trees of nuclear gene data and four-gene
      combined data, respectively) with full support values. The sister-group
      relationship of Cimicomorpha and Pentatomomorpha was also strongly supported.
      Nepomorpha originated in early Triassic and the other six infraorders originated
      in a very short period of time in middle Triassic. Cimicomorpha and
      Pentatomomorpha underwent a radiation at family level in Cretaceous, paralleling
      the proliferation of the flowering plants. Our results indicated that the higher
      group radiations within hemimetabolous Heteroptera were simultaneously with those
      of holometabolous Coleoptera and Diptera which took place in the Triassic. While
      the aquatic habitat was colonized by Nepomorpha already in the Triassic, the
      Gerromorpha independently adapted to the semi-aquatic habitat in the Early
      Jurassic.

PMID- 22384162
TI  - Predictive markers of honey bee colony collapse.
AB  - Across the Northern hemisphere, managed honey bee colonies, Apis mellifera, are
      currently affected by abrupt depopulation during winter and many factors are
      suspected to be involved, either alone or in combination. Parasites and pathogens
      are considered as principal actors, in particular the ectoparasitic mite Varroa
      destructor, associated viruses and the microsporidian Nosema ceranae. Here we
      used long term monitoring of colonies and screening for eleven disease agents and
      genes involved in bee immunity and physiology to identify predictive markers of
      honeybee colony losses during winter. The data show that DWV, Nosema ceranae,
      Varroa destructor and Vitellogenin can be predictive markers for winter colony
      losses, but their predictive power strongly depends on the season. In particular,
      the data support that V. destructor is a key player for losses, arguably in line
      with its specific impact on the health of individual bees and colonies.

PMID- 22384164
TI  - Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high
      demand for thiamin transport and antioxidant protection.
AB  - Ketogulonicigenium vulgare, though grows poorly when mono-cultured, has been
      widely used in the industrial production of the precursor of vitamin C with the
      coculture of Bacillus megaterium. Various efforts have been made to clarify the
      synergic pattern of this artificial microbial community and to improve the growth
      and production ability of K. vulgare, but there is still no sound explanation. In
      previous research, we found that the addition of reduced glutathione into K.
      vulgare monoculture could significantly improve its growth and productivity. By
      performing SEM and TEM, we observed that after adding GSH into K. vulgare
      monoculture, cells became about 4-6 folds elongated, and formed intracytoplasmic
      membranes (ICM). To explore the molecular mechanism and provide insights into the
      investigation of the synergic pattern of the co-culture system, we conducted a
      comparative iTRAQ-2-D-LC-MS/MS-based proteomic analysis of K. vulgare grown under
      reduced glutathione. Principal component analysis of proteomic data showed that
      after the addition of glutathione, proteins for thiamin/thiamin pyrophosphate
      (TPP) transport, glutathione transport and the maintenance of membrane integrity,
      together with several membrane-bound dehydrogenases had significant up
      regulation. Besides, several proteins participating in the pentose phosphate
      pathway and tricarboxylic acid cycle were also up-regulated. Additionally,
      proteins combating intracellular reactive oxygen species were also up-regulated,
      which similarly occurred in K. vulgare when the co-cultured B. megaterium cells
      lysed from our former research results. This study reveals the demand for
      transmembrane transport of substrates, especially thiamin, and the demand for
      antioxidant protection of K. vulgare.

PMID- 22384165
TI  - Estimating the impact of newly arrived foreign-born persons on tuberculosis in
      the United States.
AB  - BACKGROUND: Among approximately 163.5 million foreign-born persons admitted to
      the United States annually, only 500,000 immigrants and refugees are required to
      undergo overseas tuberculosis (TB) screening. It is unclear what extent of the
      unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in
      the United States. METHODOLOGY/PRINCIPAL FINDINGS: We defined foreign-born
      persons within 1 year after arrival in the United States as "newly arrived", and
      utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease
      Control and Prevention, and World Health Organization to estimate the incidence
      of TB among newly arrived foreign-born persons in the United States. During 2001
      through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB
      incident cases, were estimated to occur among 20,989,738 person-years for the
      1,479,542,654 newly arrived foreign-born persons in the United States. Of the
      11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and
      refugees, 36.6% (4,211) among students/exchange visitors and temporary workers,
      13.8% (1,589) among tourists and business travelers, and 7.3% (834) among
      Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival
      departure record). The top 3 newly arrived foreign-born populations with the
      largest estimated TB incident cases per 100,000 admissions were immigrants and
      refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence
      rate of >=100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95%
      confidence interval [CI], 228.3 to 243.3), students/exchange visitors and
      temporary workers from high-incidence countries (60.9 cases/100,000 admissions,
      95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence
      countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000
      population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8).
      CONCLUSIONS/SIGNIFICANCE: Newly arrived nonimmigrant visitors contribute
      substantially to the burden of foreign-born TB in the United States. To achieve
      the goals of TB elimination, direct investment in global TB control and
      strategies to target nonimmigrant visitors should be considered.

PMID- 22384166
TI  - Epstein-Barr virus stimulates torque teno virus replication: a possible
      relationship to multiple sclerosis.
AB  - Viral infections have been implicated in the pathogenesis of multiple sclerosis.
      Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate
      and torque teno virus (TTV) has also been discussed in this context.
      Nevertheless, mechanistic aspects remain unresolved. We report viral replication,
      as measured by genome amplification, as well as quantitative PCR of two TTV-HD14
      isolates isolated from multiple sclerosis brain in a series of EBV-positive and 
      negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results
      demonstrate the replication of both transfected TTV genomes up to day 21 post
      transfection in all the evaluated cell lines. Quantitative amplification
      indicates statistically significant enhanced TTV replication in the EBV-positive
      cell lines, including the EBV-converted BJAB line, in comparison to the EBV
      negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV
      infections in the replication of TTV. The present study provides information on a
      possible interaction of EBV and TTV in the etiology and progression of multiple
      sclerosis.

PMID- 22384167
TI  - NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in
      chondrosarcoma following treatment with 5-Aza-2-deoxycitabine.
AB  - BACKGROUND: Chondrosarcoma has no proven systemic option in the metastatic
      setting. The development of a non-cross-resistant strategy, such as cellular
      immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1
      and PRAME are members of the Cancer Testis Antigen (CTA) family that have been
      identified as promising targets for T cell therapy. LAGE-1 is a cancer testis
      antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope
      with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5
      Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the
      feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME
      specific T cells using 5-Aza-dC to induce antigen expression. METHODS: We used 11
      flash frozen tumors from the University of Washington tumor bank to test for the
      expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors.
      Using four chondrosarcoma cell lines we tested the expression of these CTA's with
      and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME
      specific effectors that we generated from sarcoma patients, we evaluated the
      ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in
      vitro both with and without 5-Aza-dC treatment. RESULTS: A minority (36%) of
      chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our
      reference value and none expressed PRAME at that level. However, in all four of
      the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be
      induced following treatment with 5-Aza-dC including in cell lines where
      expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and
      PRAME specific CD8+ effector T cells were able to specifically recognize and lyse
      A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.
      CONCLUSION: These data suggest that adoptive immunotherapy in combination with 5
      Aza-dC may be a potential strategy to treat unresectable or metastatic
      chondrosarcoma patients where no proven systemic therapies exist.

PMID- 22384169
TI  - Using PCR-based detection and genotyping to trace Streptococcus salivarius
      meningitis outbreak strain to oral flora of radiology physician assistant.
AB  - We recently investigated three cases of bacterial meningitis that were reported
      from a midwestern radiology clinic where facemasks were not worn during spinal
      injection of contrast agent during myelography procedures. Using pulsed field gel
      electrophoresis we linked a case strain of S. salivarius to an oral specimen of a
      radiology physician assistant (RPA). We also used a real-time PCR assay to detect
      S. salivarius DNA within a culture-negative cerebrospinal fluid (CSF) specimen.
      Here we extend this investigation through using a nested PCR/sequencing strategy
      to link the culture-negative CSF specimen to the case strain. We also provide
      validation of the real-time PCR assay used, demonstrating that it is not solely
      specific for Streptococcus salivarius, but is also highly sensitive for detection
      of the closely related oral species Streptococcus vestibularis. Through using
      multilocus sequence typing and 16S rDNA sequencing we further strengthen the link
      between the CSF case isolate and the RPA carriage isolate. We also demonstrate
      that the newly characterized strains from this study are distinct from previously
      characterized S. salivarius strains associated with carriage and meningitis.

PMID- 22384168
TI  - Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and
      implication for NF-Kappab activation.
AB  - Epstein-Barr virus (EBV) is associated with several types of cancers including
      Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent
      membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator
      of the transcription factor NF-kappaB, a property that is essential for EBV
      transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence
      variations and induction of higher NF-kappaB activation levels compared to the
      prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated
      cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to
      analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated
      NF-kappaB activation potential. We found that a number of variants mediate higher
      NF-kappaB activation levels when compared to B95-8 LMP1 and mapped three single
      polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was
      present in all LMP1 isolated in this study and its effect was variant dependent,
      suggesting that it was modulated by other polymorphisms. The two polymorphisms
      I124V and F144I were present in distinct phylogenetic groups and were linked with
      other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two
      sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of
      increased NF-kappaB activation in vitro, were not associated with EBV-associated
      HL in the SHCS. Taken together these results highlighted the importance of single
      polymorphisms for the modulation of LMP1 signaling activity and demonstrated that
      several groups of LMP1 variants, through distinct mutational paths, mediated
      enhanced NF-kappaB activation levels compared to B95-8 LMP1.

PMID- 22384170
TI  - Ascl2 knockdown results in tumor growth arrest by miRNA-302b-related inhibition
      of colon cancer progenitor cells.
AB  - BACKGROUND: Achaete scute-like 2 (Ascl2), a basic helix-loop-helix (bHLH)
      transcription factor, controls the fate of intestinal stem cells. However, the
      role of Ascl2 in colon cancer progenitor cells remains unknown. The cell line HT
      29 (47.5-95% of CD133(+) population) and LS174T (0.45% of CD133(+) population)
      were chosen for functional evaluation of Ascl2 in colon cancer progenitor cells
      after gene knockdown by RNA interference. METHODOLOGY/PRINCIPAL FINDINGS:
      Immunohistochemistry demonstrated that Ascl2 was significantly increased in
      colorectal adenocarcinomas. Downregulation of Ascl2 using RNA interference in
      cultured colonic adenocarcinoma HT-29 and LS174T cells reduced cellular
      proliferation, colony-forming ability, invasion and migration in vitro, and
      resulted in the growth arrest of tumor xenografts in vivo. The Ascl2 protein
      level in CD133(+) HT-29 cells was significantly higher than in CD133(-) HT-29
      cells. Ascl2 blockade via shRNA interference in HT-29 cells (shRNA-Ascl2/HT-29
      cells) resulted in 26.2% of cells staining CD133(+) compared with 54.7% in
      control shRNA-Ctr/HT-29 cells. The levels of 'stemness' associated genes, such as
      CD133, Sox2, Oct4, Lgr5, Bmi1, and C-myc, were significantly decreased in shRNA
      Ascl2/HT-29 and shRNA-Ascl2/LS174T cells in vitro as well as in the corresponding
      tumor xenograft (CD133 was not performed in shRNA-Ascl2/LS174T cells). The shRNA
      Ascl2/HT-29 cells had inhibited abilities to form tumorspheres compared with
      control. The microRNA (miRNAs) microarrays, identified 26 up-regulated miRNAs and
      58 down-regulated miRNAs in shRNA-Ascl2/HT-29 cells. Expression levels of let-7b,
      miRNA-124, miRNA-125b, miRNA-17, miRNA-20a and miRNA-302b, involved in the
      regulation of 'stemness', were quantified with qPCR, which confirmed their
      identities. Restoration of miRNA-302b, via its mimic, led to the restoration of
      shRNA-Ascl2/HT-29 'stemness' characteristics, including tumorsphere formation and
      'stemness' associated genes levels, and the recovery of cellular behaviors,
      including colony-forming ability, invasion and migration in vitro.
      CONCLUSIONS/SIGNIFICANCE: Ascl2 may be a potential target for the inhibition of
      colon cancer progenitor cells, and functions through a miR-302b-related
      mechanism.

PMID- 22384171
TI  - The Max b-HLH-LZ can transduce into cells and inhibit c-Myc transcriptional
      activities.
AB  - The inhibition of the functions of c-Myc (endogenous and oncogenic) was recently
      shown to provide a spectacular therapeutic index in cancer mouse models, with
      complete tumor regression and minimal side-effects in normal tissues. This was
      achieved by the systemic and conditional expression of omomyc, the cDNA of a
      designed mutant of the b-HLH-LZ of c-Myc named Omomyc. The overall mode of action
      of Omomyc consists in the sequestration of Max and the concomitant competition of
      the Omomyc/Max complex with the endogenous c-Myc/Max heterodimer. This leads to
      the inhibition of the transactivation of Myc target genes involved in
      proliferation and metabolism. While this body of work has provided extraordinary
      insights to guide the future development of new cancer therapies that target c
      Myc, Omomyc itself is not a therapeutic agent. In this context, we sought to
      exploit the use of a b-HLH-LZ to inhibit c-Myc in a cancer cell line in a more
      direct fashion. We demonstrate that the b-HLH-LZ domain of Max (Max*) behaves as
      a bona fide protein transduction domain (PTD) that can efficiently transduce
      across cellular membrane via through endocytosis and translocate to the nucleus.
      In addition, we show that the treatment of HeLa cells with Max* leads to a
      reduction of metabolism and proliferation rate. Accordingly, we observe a
      decrease of the population of HeLa cells in S phase, an accumulation in G1/G0 and
      the induction of apoptosis. In agreement with these phenotypic changes, we show
      by q-RT-PCR that the treatment of HeLa cells with Max* leads to the activation of
      the transcription c-Myc repressed genes as well as the repression of the
      expression of c-Myc activated genes. In addition to the novel discovery that the
      Max b-HLH-LZ is a PTD, our findings open up new avenues and strategies for the
      direct inhibition of c-Myc with b-HLH-LZ analogs.

PMID- 22384172
TI  - Characterization of synaptically connected nuclei in a potential sensorimotor
      feedback pathway in the zebra finch song system.
AB  - Birdsong is a learned behavior that is controlled by a group of identified
      nuclei, known collectively as the song system. The cortical nucleus HVC (used as
      a proper name) is a focal point of many investigations as it is necessary for
      song production, song learning, and receives selective auditory information. HVC
      receives input from several sources including the cortical area MMAN (medial
      magnocellular nucleus of the nidopallium). The MMAN to HVC connection is
      particularly interesting as it provides potential sensorimotor feedback to HVC.
      To begin to understand the role of this connection, we investigated the
      physiological relation between MMAN and HVC activity with simultaneous multiunit
      extracellular recordings from these two nuclei in urethane anesthetized zebra
      finches. As previously reported, we found similar timing in spontaneous bursts of
      activity in MMAN and HVC. Like HVC, MMAN responds to auditory playback of the
      bird's own song (BOS), but had little response to reversed BOS or conspecific
      song. Stimulation of MMAN resulted in evoked activity in HVC, indicating
      functional excitation from MMAN to HVC. However, inactivation of MMAN resulted in
      no consistent change in auditory responses in HVC. Taken together, these results
      indicate that MMAN provides functional excitatory input to HVC but does not
      provide significant auditory input to HVC in anesthetized animals. We hypothesize
      that MMAN may play a role in motor reinforcement or coordination, or may provide
      modulatory input to the song system about the internal state of the animal as it
      receives input from the hypothalamus.

PMID- 22384173
TI  - Biophysical characterization and membrane interaction of the two fusion loops of
      glycoprotein B from herpes simplex type I virus.
AB  - The molecular mechanism of entry of herpesviruses requires a multicomponent
      fusion system. Cell invasion by Herpes simplex virus (HSV) requires four virally
      encoded glycoproteins: namely gD, gB and gH/gL. The role of gB has remained
      elusive until recently when the crystal structure of HSV-1 gB became available
      and the fusion potential of gB was clearly demonstrated. Although much
      information on gB structure/function relationship has been gathered in recent
      years, the elucidation of the nature of the fine interactions between gB fusion
      loops and the membrane bilayer may help to understand the precise molecular
      mechanism behind herpesvirus-host cell membrane fusion. Here, we report the first
      biophysical study on the two fusion peptides of gB, with a particular focus on
      the effects determined by both peptides on lipid bilayers of various
      compositions. The two fusion loops constitute a structural subdomain wherein key
      hydrophobic amino acids form a ridge that is supported on both sides by charged
      residues. When used together the two fusion loops have the ability to
      significantly destabilize the target membrane bilayer, notwithstanding their low
      bilayer penetration when used separately. These data support the model of gB
      fusion loops insertion into cholesterol enriched membranes.

PMID- 22384174
TI  - Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among
      South Indian Women.
AB  - Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic
      disorder in which hyperinsulinemia and peripheral insulin resistance are central
      features. Given the physiological overlap between PCOS and type-2 diabetes
      (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number
      of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory
      results. Our study is first of its kind to investigate the association pattern of
      CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women.
      250 PCOS cases and 299 controls from Southern India were recruited for this
      study. Allele and genotype frequencies of the SNPs were determined and compared
      between the cases and controls. Results show significant association of UCSNP-44
      genotype CC with PCOS (p = 0.007) with highly significant odds ratio when
      compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61) as well as TT (OR =
      1.94, p = 0.016, 95% CI = 1.13-3.34). While the haplotype carrying the SNP-44 and
      SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR =
      2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221)
      seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results
      support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene
      in the manifestation of PCOS.

PMID- 22384175
TI  - Discovering dysfunction of multiple microRNAs cooperation in disease by a
      conserved microRNA co-expression network.
AB  - MicroRNAs, a new class of key regulators of gene expression, have been shown to
      be involved in diverse biological processes and linked to many human diseases. To
      elucidate miRNA function from a global perspective, we constructed a conserved
      miRNA co-expression network by integrating multiple human and mouse miRNA
      expression data. We found that these conserved co-expressed miRNA pairs tend to
      reside in close genomic proximity, belong to common families, share common
      transcription factors, and regulate common biological processes by targeting
      common components of those processes based on miRNA targets and miRNA
      knockout/transfection expression data, suggesting their strong functional
      associations. We also identified several co-expressed miRNA sub-networks. Our
      analysis reveals that many miRNAs in the same sub-network are associated with the
      same diseases. By mapping known disease miRNAs to the network, we identified
      three cancer-related miRNA sub-networks. Functional analyses based on targets and
      miRNA knockout/transfection data consistently show that these sub-networks are
      significantly involved in cancer-related biological processes, such as apoptosis
      and cell cycle. Our results imply that multiple co-expressed miRNAs can
      cooperatively regulate a given biological process by targeting common components
      of that process, and the pathogenesis of disease may be associated with the
      abnormality of multiple functionally cooperative miRNAs rather than individual
      miRNAs. In addition, many of these co-expression relationships provide strong
      evidence for the involvement of new miRNAs in important biological processes,
      such as apoptosis, differentiation and cell cycle, indicating their potential
      disease links.

PMID- 22384176
TI  - Optimal use of conservation and accessibility filters in microRNA target
      prediction.
AB  - It is generally accepted that filtering microRNA (miRNA) target predictions by
      conservation or by accessibility can reduce the false discovery rate. However,
      these two strategies are usually not exploited in a combined and flexible manner.
      Here, we introduce PACCMIT, a flexible method that filters miRNA binding sites by
      their conservation, accessibility, or both. The improvement in performance
      obtained with each of these three filters is demonstrated on the prediction of
      targets for both i) highly and ii) weakly conserved miRNAs, i.e., in two
      scenarios in which the miRNA-target interactions are subjected to different
      evolutionary pressures. We show that in the first scenario conservation is a
      better filter than accessibility (as both sensitivity and precision are higher
      among the top predictions) and that the combined filter improves performance of
      PACCMIT even further. In the second scenario, on the other hand, the
      accessibility filter performs better than both the conservation and combined
      filters, suggesting that the site conservation is not equally effective in
      rejecting false positive predictions for all miRNAs. Regarding the quality of the
      ranking criterion proposed by Robins and Press and used in PACCMIT, it is shown
      that top ranking interactions correspond to more downregulated proteins than do
      the lower ranking interactions. Comparison with several other target prediction
      algorithms shows that the ranking of predictions provided by PACCMIT is at least
      as good as the ranking generated by other conservation-based methods and
      considerably better than the energy-based ranking used in other accessibility
      based methods.

PMID- 22384177
TI  - Monkeys monitor human goals in a nonmatch-to-goal interactive task.
AB  - We designed a new task, called nonmatch-to-goal, to study the ability of macaque
      monkeys to interact with humans in a rule-guided paradigm. In this task the
      monkeys were required to choose one of two targets, from a list of three. For
      each choice, they were required to switch from their choice on the previous trial
      to a different one. In a subset of trials the monkeys observed a human partner
      performing the task. When the human concluded his turn, the monkeys were required
      to switch to a new goal discarding the human's previous goal. We found that
      monkeys were very skillful in monitoring goals, not only of their own choice by
      also those of their human partner. They showed also a surprising ability to
      coordinate their actions, taking turns with the human partner, starting and
      stopping their own turn following the decision of the human partner in the task.

PMID- 22384178
TI  - Markov dynamics as a zooming lens for multiscale community detection: non clique
      like communities and the field-of-view limit.
AB  - In recent years, there has been a surge of interest in community detection
      algorithms for complex networks. A variety of computational heuristics, some with
      a long history, have been proposed for the identification of communities or,
      alternatively, of good graph partitions. In most cases, the algorithms maximize a
      particular objective function, thereby finding the 'right' split into
      communities. Although a thorough comparison of algorithms is still lacking, there
      has been an effort to design benchmarks, i.e., random graph models with known
      community structure against which algorithms can be evaluated. However, popular
      community detection methods and benchmarks normally assume an implicit notion of
      community based on clique-like subgraphs, a form of community structure that is
      not always characteristic of real networks. Specifically, networks that emerge
      from geometric constraints can have natural non clique-like substructures with
      large effective diameters, which can be interpreted as long-range communities. In
      this work, we show that long-range communities escape detection by popular
      methods, which are blinded by a restricted 'field-of-view' limit, an intrinsic
      upper scale on the communities they can detect. The field-of-view limit means
      that long-range communities tend to be overpartitioned. We show how by adopting a
      dynamical perspective towards community detection [1], [2], in which the
      evolution of a Markov process on the graph is used as a zooming lens over the
      structure of the network at all scales, one can detect both clique- or non clique
      like communities without imposing an upper scale to the detection. Consequently,
      the performance of algorithms on inherently low-diameter, clique-like benchmarks
      may not always be indicative of equally good results in real networks with local,
      sparser connectivity. We illustrate our ideas with constructive examples and
      through the analysis of real-world networks from imaging, protein structures and
      the power grid, where a multiscale structure of non clique-like communities is
      revealed.

PMID- 22384179
TI  - Waist circumference adjusted for body mass index and intra-abdominal fat mass.
AB  - BACKGROUND: The association between waist circumference (WC) and mortality is
      particularly strong and direct when adjusted for body mass index (BMI). One
      conceivable explanation for this association is that WC adjusted for BMI is a
      better predictor of the presumably most harmful intra-abdominal fat mass (IAFM)
      than WC alone. We studied the prediction of abdominal subcutaneous fat mass
      (ASFM) and IAFM by WC alone and by addition of BMI as an explanatory factor.
      METHODOLOGY/PRINCIPAL FINDINGS: WC, BMI and magnetic resonance imaging data from
      742 men and women who participated in clinical studies in Canada and Finland were
      pooled. Total adjusted squared multiple correlation coefficients (R(2)) of ASFM
      and IAFM were calculated from multiple linear regression models with WC and BMI
      as explanatory variables. Mean BMI and WC of the participants in the pooled
      sample were 30 kg/m(2) and 102 cm, respectively. WC explained 29% of the variance
      in ASFM and 51% of the variance in IAFM. Addition of BMI to WC added 28% to the
      variance explained in ASFM, but only 1% to the variance explained in IAFM.
      Results in subgroups stratified by study center, sex, age, obesity level and type
      2 diabetes status were not systematically different. CONCLUSION/SIGNIFICANCE: The
      prediction of IAFM by WC is not improved by addition of BMI.

PMID- 22384180
TI  - Arsenic trioxide exerts antimyeloma effects by inhibiting activity in the
      cytoplasmic substrates of histone deacetylase 6.
AB  - Arsenic trioxide (As(2)O(3)) has shown remarkable efficacy for the treatment of
      multiple myeloma (MM). Histone deacetylases (HDAC) play an important role in the
      control of gene expression, and their dysregulation has been linked to myeloma.
      Especially, HDAC6, a unique cytoplasmic member of class II, which mainly
      functions as alpha-tubulin deacetylase and Hsp90 deacetylase, has become a target
      for drug development to treat cancer due to its major contribution in oncogenic
      cell transformation. However, the mechanisms of action for As(2)O(3) have not yet
      been defined. In this study, we investigated the effect of As(2)O(3) on
      proliferation and apoptosis in human myeloma cell line and primary myeloma cells,
      and then we studied that As(2)O(3) exerts antimyeloma effects by inhibiting
      activity in the alpha-tubulin and Hsp90 through western blot analysis and
      immunoprecipitation. We found that As(2)O(3) acts directly on MM cells at
      relatively low concentrations of 0.5~2.5 uM, which effects survival and apoptosis
      of MM cells. However, As(2)O(3) inhibited HDAC activity at the relatively high
      concentration and dose-dependent manner (great than 4 uM). Subsequently, we found
      that As(2)O(3) treatment in a dose- and time-dependent fashion markedly increased
      the level of acetylated alpha-tubulin and acetylated Hsp90, and inhibited the
      chaperone association with IKKalpha activities and increased degradation of
      IKKalpha. Importantly, the loss of IKKalpha-associated Hsp90 occurred prior to
      any detectable loss in the levels of IKKalpha, indicating a novel pathway by
      which As(2)O(3) down-regulates HDAC6 to destabilize IKKalpha protein via Hsp90
      chaperone function. Furthermore, we observed the effect of As(2)O(3) on TNF-alpha
      induced NF-kappaB signaling pathway was to significantly reduced phosphorylation
      of Ser-536 on NF-kappaB p65. Therefore, our studies provide an important insight
      into the molecular mechanism of anti-myeloma activity of As(2)O(3) in HDAC6-Hsp90
      IKKalpha-NFkappaB signaling axis and the rationale for As(2)O(3) can be extended
      readily using all the HDAC associated diseases.

PMID- 22384181
TI  - NCAM180 regulates Ric8A membrane localization and potentiates beta-adrenergic
      response.
AB  - Cooperation between receptors allows integrated intracellular signaling leading
      to appropriate physiological responses. The Neural Cell Adhesion Molecule (NCAM)
      has three main isoforms of 120, 140 and 180 kDa, with adhesive and signaling
      properties, but their respective functions remains to be fully identified. Here
      we show that the human NCAM180 intracellular domain is a novel interactor of the
      human guanosine exchange factor (GEF) Ric8A using the yeast two hybrid system and
      immunoprecipitation. Furthermore, NCAM, Ric8A and G(alphas) form a tripartite
      complex. Colocalization experiments by confocal microscopy revealed that human
      NCAM180 specifically induces the recruitment of Ric8A to the membrane. In
      addition, using an in vitro recombinant system, and in vivo by comparing NCAM
      knock-out mouse brain to NCAM heterozygous and wild type brains, we show that
      NCAM expression dose dependently regulates Ric8A redistribution in detergent
      resistent membrane microdomains (DRM). Previous studies have demonstrated
      essential roles for Ric8 in G(alpha) protein activity at G protein coupled
      receptors (GPCR), during neurotransmitter release and for asymmetric cell
      division. We observed that inhibition of Ric8A by siRNA or its overexpression,
      decreases or increases respectively, cAMP production following beta-adrenergic
      receptor stimulation. Furthermore, in human HEK293T recombinant cells, NCAM180
      potentiates the G(alphas) coupled beta-adrenergic receptor response, in a Ric8A
      dependent manner, whereas NCAM120 or NCAM140 do not. Finally, in mouse
      hippocampal neurons expressing endogenously NCAM, NCAM is required for the
      agonist isoproterenol to induce cAMP production, and this requirement depends on
      Ric8A. These data illustrate a functional crosstalk between a GPCR and an IgCAM
      in the nervous system.

PMID- 22384182
TI  - Structural characterisation of Tpx from Yersinia pseudotuberculosis reveals
      insights into the binding of salicylidene acylhydrazide compounds.
AB  - Thiol peroxidase, Tpx, has been shown to be a target protein of the salicylidene
      acylhydrazide class of antivirulence compounds. In this study we present the
      crystal structures of Tpx from Y. pseudotuberculosis (ypTpx) in the oxidised and
      reduced states, together with the structure of the C61S mutant. The structures
      solved are consistent with previously solved atypical 2-Cys thiol peroxidases,
      including that for "forced" reduced states using the C61S mutant. In addition, by
      investigating the solution structure of ypTpx using small angle X-ray scattering
      (SAXS), we have confirmed that reduced state ypTpx in solution is a homodimer.
      The solution structure also reveals flexibility around the dimer interface.
      Notably, the conformational changes observed between the redox states at the
      catalytic triad and at the dimer interface have implications for substrate and
      inhibitor binding. The structural data were used to model the binding of two
      salicylidene acylhydrazide compounds to the oxidised structure of ypTpx. Overall,
      the study provides insights into the binding of the salicylidene acylhydrazides
      to ypTpx, aiding our long-term strategy to understand the mode of action of this
      class of compounds.

PMID- 22384183
TI  - Improving the MVA vaccine potential by deleting the viral gene coding for the IL
      18 binding protein.
AB  - BACKGROUND: Modified Vaccinia Ankara (MVA) is an attenuated strain of Vaccinia
      virus (VACV) currently employed in many clinical trials against HIV/AIDS and
      other diseases. MVA still retains genes involved in host immune response evasion,
      enabling its optimization by removing some of them. The aim of this study was to
      evaluate cellular immune responses (CIR) induced by an IL-18 binding protein gene
      (C12L) deleted vector (MVADeltaC12L). METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and
      C57BL/6 mice were immunized with different doses of MVADeltaC12L or MVA wild type
      (MVAwt), then CIR to VACV epitopes in immunogenic proteins were evaluated in
      spleen and draining lymph nodes at acute and memory phases (7 and 40 days post
      immunization respectively). Compared with parental MVAwt, MVADeltaC12L
      immunization induced a significant increase of two to three-fold in CD8(+) and
      CD4(+) T-cell responses to different VACV epitopes, with increased percentage of
      anti-VACV cytotoxic CD8(+) T-cells (CD107a/b(+)) during the acute phase of the
      response. Importantly, the immunogenicity enhancement was also observed after
      MVADeltaC12L inoculation with different viral doses and by distinct routes
      (systemic and mucosal). Potentiation of MVA's CIR was also observed during the
      memory phase, in correlation with a higher protection against an intranasal
      challenge with VACV WR. Of note, we could also show a significant increase in the
      CIR against HIV antigens such as Env, Gag, Pol and Nef from different subtypes
      expressed from two recombinants of MVADeltaC12L during heterologous DNA prime/MVA
      boost vaccination regimens. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the
      relevance of IL-18 bp contribution in the immune response evasion during MVA
      infection. Our findings clearly show that the deletion of the viral IL-18 bp gene
      is an effective approach to increase MVA vaccine efficacy, as immunogenicity
      improvements were observed against vector antigens and more importantly to HIV
      antigens.

PMID- 22384184
TI  - Effect of the citrus lycopene beta-cyclase transgene on carotenoid metabolism in
      transgenic tomato fruits.
AB  - Lycopene beta-cyclase (LYCB) is the key enzyme for the synthesis of beta
      carotene, a valuable component of the human diet. In this study, tomato
      constitutively express Lycb-1 was engineered. The beta-carotene level of
      transformant increased 4.1 fold, and the total carotenoid content increased by
      30% in the fruits. In the transgenic line, the downstream alpha-branch metabolic
      fluxes were repressed during the three developmental stages while alpha-carotene
      content increased in the ripe stage. Microarray analysis in the ripe stage
      revealed that the constitutive expression of Lycb-1 affected a number of pathways
      including the synthesis of fatty acids, flavonoids and phenylpropanoids, the
      degradation of limonene and pinene, starch and sucrose metabolism and
      photosynthesis. This study provided insight into the regulatory effect of Lycb-1
      gene on plant carotenoid metabolism and fruit transcriptome.

PMID- 22384185
TI  - Skeletal muscle PGC-1alpha is required for maintaining an acute LPS-induced
      TNFalpha response.
AB  - Many lifestyle-related diseases are associated with low-grade inflammation and
      peroxisome proliferator activated receptor gamma coactivator (PGC)-1alpha has
      been suggested to be protective against low-grade inflammation. However, whether
      these anti-inflammatory properties affect acute inflammation is not known. The
      aim of the present study was therefore to investigate the role of muscle PGC
      1alpha in acute inflammation. Quadriceps muscles were removed from 10-week old
      whole body PGC-1alpha knockout (KO), muscle specific PGC-1alpha KO (MKO) and
      muscle-specific PGC-1alpha overexpression mice (TG), 2 hours after an
      intraperitoneal injection of either 0.8 ug LPS/g body weight or saline. Basal
      TNFalpha mRNA content was lower in skeletal muscle of whole body PGC-1alpha KO
      mice and in accordance TG mice showed increased TNFalpha mRNA and protein level
      relative to WT, indicating a possible PGC-1alpha mediated regulation of TNFalpha.
      Basal p65 phosphorylation was increased in TG mice possibly explaining the
      elevated TNFalpha expression in these mice. Systemically, TG mice had reduced
      basal plasma TNFalpha levels compared with WT suggesting a protective effect
      against systemic low-grade inflammation in these animals. While TG mice reached
      similar TNFalpha levels as WT and showed more marked induction in plasma TNFalpha
      than WT after LPS injection, MKO PGC-1alpha mice had a reduced plasma TNFalpha
      and skeletal muscle TNFalpha mRNA response to LPS. In conclusion, the present
      findings suggest that PGC-1alpha enhances basal TNFalpha expression in skeletal
      muscle and indicate that PGC-1alpha does not exert anti-inflammatory effects
      during acute inflammation. Lack of skeletal muscle PGC-1alpha seems however to
      impair the acute TNFalpha response, which may reflect a phenotype more
      susceptible to infections as also observed in type 2 diabetes patients.

PMID- 22384186
TI  - Dual role of respiratory syncytial virus glycoprotein fragment as a mucosal
      immunogen and chemotactic adjuvant.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory
      tract disease in infancy and early childhood. Despite its importance as a
      pathogen, there is no licensed vaccine to prevent RSV infection. The G
      glycoprotein of RSV, a major attachment protein, is a potentially important
      target for protective antiviral immune responses and has been shown to exhibit
      chemotactic activity through CX3C mimicry. Here, we show that sublingual or
      intranasal immunization of a purified G protein fragment of amino acids from 131
      to 230, designated Gcf, induces strong serum IgG and mucosal IgA responses.
      Interestingly, these antibody responses could be elicited by Gcf even in the
      absence of any adjuvant, indicating a novel self-adjuvanting property of our
      vaccine candidate. Gcf exhibited potent chemotactic activity in in vitro cell
      migration assay and cysteine residues are necessary for chemotactic activity and
      self-adjuvanticity of Gcf in vivo. Mucosal immunization with Gcf also provides
      protection against RSV challenge without any significant lung eosinophilia or
      vaccine-induced weight loss. Together, our data demonstrate that mucosal
      administration of Gcf vaccine elicits beneficial protective immunity and
      represents a promising vaccine regimen preventing RSV infection.

PMID- 22384187
TI  - Rock art at the pleistocene/holocene boundary in Eastern South America.
AB  - BACKGROUND: Most investigations regarding the first americans have primarily
      focused on four themes: when the New World was settled by humans; where they came
      from; how many migrations or colonization pulses from elsewhere were involved in
      the process; and what kinds of subsistence patterns and material culture they
      developed during the first millennia of colonization. Little is known, however,
      about the symbolic world of the first humans who settled the New World, because
      artistic manifestations either as rock-art, ornaments, and portable art objects
      dated to the Pleistocene/Holocene transition are exceedingly rare in the
      Americas. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a pecked anthropomorphic
      figure engraved in the bedrock of Lapa do Santo, an archaeological site located
      in Central Brazil. The horizontal projection of the radiocarbon ages obtained at
      the north profile suggests a minimum age of 9,370 +/- 40 BP, (cal BP 10,700 to
      10,500) for the petroglyph that is further supported by optically stimulated
      luminescence (OSL) dates from sediment in the same stratigraphic unit, located
      between two ages from 11.7 +/- 0.8 ka BP to 9.9 +/- 0.7 ka BP. CONCLUSIONS: These
      data allow us to suggest that the anthropomorphic figure is the oldest reliably
      dated figurative petroglyph ever found in the New World, indicating that cultural
      variability during the Pleistocene/Holocene boundary in South America was not
      restricted to stone tools and subsistence, but also encompassed the symbolic
      dimension.

PMID- 22384188
TI  - Primitive duplicate Hox clusters in the European eel's genome.
AB  - The enigmatic life cycle and elongated body of the European eel (Anguilla
      anguilla L., 1758) have long motivated scientific enquiry. Recently, eel research
      has gained in urgency, as the population has dwindled to the point of critical
      endangerment. We have assembled a draft genome in order to facilitate advances in
      all provinces of eel biology. Here, we use the genome to investigate the eel's
      complement of the Hox developmental transcription factors. We show that unlike
      any other teleost fish, the eel retains fully populated, duplicate Hox clusters,
      which originated at the teleost-specific genome duplication. Using mRNA
      sequencing and in situ hybridizations, we demonstrate that all copies are
      expressed in early embryos. Theories of vertebrate evolution predict that the
      retention of functional, duplicate Hox genes can give rise to additional
      developmental complexity, which is not immediately apparent in the adult.
      However, the key morphological innovation elsewhere in the eel's life history
      coincides with the evolutionary origin of its Hox repertoire.

PMID- 22384189
TI  - Discordance between liver biopsy and Fibroscan(r) in assessing liver fibrosis in
      chronic hepatitis b: risk factors and influence of necroinflammation.
AB  - BACKGROUND: Few studies have investigated predictors of discordance between liver
      biopsy (LB) and liver stiffness measurement (LSM) using FibroScan(r). We assessed
      predictors of discordance between LB and LSM in chronic hepatitis B (CHB) and
      investigated the effects of necroinflammatory activity. METHODS: In total, 150
      patients (107 men, 43 women) were prospectively enrolled. Only LSM with >= 10
      valid measurements was considered reliable. Liver fibrosis was evaluated using
      the Laennec system. LB specimens <15 mm in length were considered ineligible.
      Reference cutoff LSM values to determine discordance were calculated from our
      cohort (6.0 kPa for >= F2, 7.5 kPa for >= F3, and 9.4 kPa for F4). RESULTS: A
      discordance, defined as a discordance of at least two stages between LB and LSM,
      was identified in 21 (14.0%) patients. In multivariate analyses, fibrosis stages
      F3-4 and F4 showed independent negative associations with discordance (P = 0.002;
      hazard ratio [HR], 0.073; 95% confidence interval [CI], 0.014-0.390 for F3-4 and
      P = 0.014; HR, 0.067; 95% CI, 0.008-0.574 for F4). LSM values were not
      significantly different between maximal activity grades 1-2 and 3-4 in F1 and F2
      fibrosis stages, whereas LSM values were significantly higher in maximal activity
      grade 3-4 than 1-2 in F3 and F4 fibrosis stage (median 8.6 vs. 11.3 kPa in F3, P
      = 0.049; median 11.9 vs. 19.2 kPa in F4, P = 0.009). CONCLUSION: Advanced
      fibrosis stage (F3-4) or cirrhosis (F4) showed a negative correlation with
      discordance between LB and LSM in patients with CHB, and maximal activity grade 3
      4 significantly influenced LSM values in F3 and F4.

PMID- 22384190
TI  - Impacts of parasites in early life: contrasting effects on juvenile growth for
      different family members.
AB  - Parasitism experienced early in ontogeny can have a major impact on host growth,
      development and future fitness, but whether siblings are affected equally by
      parasitism is poorly understood. In birds, hatching asynchrony induced by
      hormonal or behavioural mechanisms largely under parental control might
      predispose young to respond to infection in different ways. Here we show that
      parasites can have different consequences for offspring depending on their
      position in the family hierarchy. We experimentally treated European Shag
      (Phalacrocorax aristoteli) nestlings with the broad-spectrum anti-parasite drug
      ivermectin and compared their growth rates with nestlings from control broods.
      Average growth rates measured over the period of linear growth (10 days to 30
      days of age) and survival did not differ for nestlings from treated and control
      broods. However, when considering individuals within broods, parasite treatment
      reversed the patterns of growth for individual family members: last-hatched
      nestlings grew significantly slower than their siblings in control nests but grew
      faster in treated nests. This was at the expense of their earlier-hatched brood
      mates, who showed an overall growth rate reduction relative to last-hatched
      nestlings in treated nests. These results highlight the importance of exploring
      individual variation in the costs of infection and suggest that parasites could
      be a key factor modulating within-family dynamics, sibling competition and
      developmental trajectories from an early age.

PMID- 22384191
TI  - Barcoding human physical activity to assess chronic pain conditions.
AB  - BACKGROUND: Modern theories define chronic pain as a multidimensional experience 
      the result of complex interplay between physiological and psychological factors
      with significant impact on patients' physical, emotional and social functioning.
      The development of reliable assessment tools capable of capturing the
      multidimensional impact of chronic pain has challenged the medical community for
      decades. A number of validated tools are currently used in clinical practice
      however they all rely on self-reporting and are therefore inherently subjective.
      In this study we show that a comprehensive analysis of physical activity (PA)
      under real life conditions may capture behavioral aspects that may reflect
      physical and emotional functioning. METHODOLOGY: PA was monitored during five
      consecutive days in 60 chronic pain patients and 15 pain-free healthy subjects.
      To analyze the various aspects of pain-related activity behaviors we defined the
      concept of PA 'barcoding'. The main idea was to combine different features of PA
      (type, intensity, duration) to define various PA states. The temporal sequence of
      different states was visualized as a 'barcode' which indicated that significant
      information about daily activity can be contained in the amount and variety of PA
      states, and in the temporal structure of sequence. This information was
      quantified using complementary measures such as structural complexity metrics
      (information and sample entropy, Lempel-Ziv complexity), time spent in PA states,
      and two composite scores, which integrate all measures. The reliability of these
      measures to characterize chronic pain conditions was assessed by comparing groups
      of subjects with clinically different pain intensity. CONCLUSION: The defined
      measures of PA showed good discriminative features. The results suggest that
      significant information about pain-related functional limitations is captured by
      the structural complexity of PA barcodes, which decreases when the intensity of
      pain increases. We conclude that a comprehensive analysis of daily-life PA can
      provide an objective appraisal of the intensity of pain.

PMID- 22384192
TI  - FoxO1 gain of function in the pancreas causes glucose intolerance, polycystic
      pancreas, and islet hypervascularization.
AB  - Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the
      pancreas causes diabetes. FoxO1 is a downstream transcription factor of
      insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency
      restored beta cell mass and rescued diabetes in IRS2 knockout mice. However, it
      is still unclear whether FoxO1 dysregulation in the pancreas could be the cause
      of diabetes. To test this hypothesis, we generated transgenic mice overexpressing
      constitutively active FoxO1 specifically in the pancreas (TG). TG mice had
      impaired glucose tolerance and some of them indeed developed diabetes due to the
      reduction of beta cell mass, which is associated with decreased Pdx1 and MafA in
      beta cells. We also observed increased proliferation of pancreatic duct
      epithelial cells in TG mice and some mice developed a polycystic pancreas as they
      aged. Furthermore, TG mice exhibited islet hypervascularities due to increased
      VEGF-A expression in beta cells. We found FoxO1 binds to the VEGF-A promoter and
      regulates VEGF-A transcription in beta cells. We propose that dysregulation of
      FoxO1 activity in the pancreas could account for the development of diabetes and
      pancreatic cysts.

PMID- 22384193
TI  - Food chain transport of nanoparticles affects behaviour and fat metabolism in
      fish.
AB  - Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical
      advances over the bulk material. The use of nanoparticles in cosmetics,
      detergents, food and other commercial products is rapidly increasing despite
      little knowledge of their effect on organism metabolism. We show here that
      commercially manufactured polystyrene nanoparticles, transported through an
      aquatic food chain from algae, through zooplankton to fish, affect lipid
      metabolism and behaviour of the top consumer. At least three independent
      metabolic parameters differed between control and test fish: the weight loss, the
      triglycerides?cholesterol ratio in blood serum, and the distribution of
      cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles
      bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from
      properly utilising their fat reserves if absorbed through ingestion. In addition
      to the metabolic effects, we show that consumption of nanoparticle-containing
      zooplankton affects the feeding behaviour of the fish. The time it took the fish
      to consume 95% of the food presented to them was more than doubled for
      nanoparticle-exposed compared to control fish. Since many nano-sized products
      will, through the sewage system, end up in freshwater and marine habitats, our
      study provides a potential bioassay for testing new nano-sized material before
      manufacturing. In conclusion, our study shows that from knowledge of the
      molecular composition of the protein corona around nanoparticles it is possible
      to make a testable molecular hypothesis and bioassay of the potential biological
      risks of a defined nanoparticle at the organism and ecosystem level.

PMID- 22384194
TI  - Mercury in Nelson's Sparrow subspecies at breeding sites.
AB  - BACKGROUND: Mercury is a persistent, biomagnifying contaminant that can cause
      negative effects on ecosystems. Marshes are often areas of relatively high
      mercury methylation and bioaccumulation. Nelson's Sparrows (Ammodramus nelsoni)
      use marsh habitats year-round and have been documented to exhibit tissue mercury
      concentrations that exceed negative effects thresholds. We sought to further
      characterize the potential risk of Nelson's Sparrows to mercury exposure by
      sampling individuals from sites within the range of each of its subspecies.
      METHODOLOGY/PRINCIPAL FINDINGS: From 2009 to 2011, we captured adult Nelson's
      Sparrows at sites within the breeding range of each subspecies (A. n. nelsoni:
      Grand Forks and Upham, North Dakota; A. n. alterus: Moosonee, Ontario; and A. n.
      subvirgatus: Grand Manan Island, New Brunswick) and sampled breast feathers, the
      first primary feather (P1), and blood for total mercury analysis. Mean blood
      mercury in nelsoni individuals captured near Grand Forks ranged from 0.84 +/-
      0.37 to 1.65 +/- 1.02 SD ppm among years, between 2.0 and 4.9 times as high as
      concentrations at the other sites (P<0.01). Breast feather mercury did not vary
      among sites within a given sampling year (site means ranged from 0.98 +/- 0.69 to
      2.71 +/- 2.93 ppm). Mean P1 mercury in alterus (2.96 +/- 1.84 ppm fw) was
      significantly lower than in any other sampled population (5.25 +/- 2.24-6.77 +/-
      3.51 ppm; P <= 0.03). CONCLUSIONS/SIGNIFICANCE: Our study further characterized
      mercury in Nelson's Sparrows near Grand Forks; we documented localized and
      potentially harmful mercury concentrations, indicating that this area may
      represent a biological mercury hotspot. This finding warrants further research to
      determine if wildlife populations of conservation or recreational interest in
      this area may be experiencing negative effects due to mercury exposure. We
      present preliminary conclusions about the risk of each sampled population to
      mercury exposure.

PMID- 22384195
TI  - Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric
      ischemia/reperfusion injury.
AB  - Several innate and adaptive immune cell types participate in ischemia/reperfusion
      induced tissue injury. Amongst them, platelets have received little attention as
      contributors in the process of tissue damage after ischemia reperfusion (I/R)
      injury. It is currently unknown whether platelets participate through the
      immunologically important molecules including, CD40 and when activated, CD154
      (CD40L), in the pathogenesis of I/R injury. We hypothesized that constitutive
      expression of CD40 and activation-induced expression of CD154 on platelets
      mediate local mesenteric and remote lung tissue damage after I/R injury. Wild
      type (WT; C57BL/6J), CD40 and CD154 deficient mice underwent mesenteric ischemia
      for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to
      mesenteric I/R injury displayed both local intestinal and remote lung damage. In
      contrast, there was significantly less intestinal damage and no remote lung
      injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet
      depleted WT mice transfused with platelets from CD40 or CD154 deficient mice
      failed to reconstitute remote lung damage. In contrast, when CD40 or CD154
      deficient mice were transfused with WT platelets lung tissue damage was re
      established. Together, these findings suggest that multiple mechanisms are
      involved in local and remote tissue injury and also identify platelet-expressed
      CD40 and/or CD154 as mediators of remote tissue damage.

PMID- 22384196
TI  - Integrin-specific mechanoresponses to compression and extension probed by
      cylindrical flat-ended AFM tips in lung cells.
AB  - Cells from lung and other tissues are subjected to forces of opposing directions
      that are largely transmitted through integrin-mediated adhesions. How cells
      respond to force bidirectionality remains ill defined. To address this question,
      we nanofabricated flat-ended cylindrical Atomic Force Microscopy (AFM) tips with
      ~1 um(2) cross-section area. Tips were uncoated or coated with either integrin
      specific (RGD) or non-specific (RGE/BSA) molecules, brought into contact with
      lung epithelial cells or fibroblasts for 30 s to form focal adhesion precursors,
      and used to probe cell resistance to deformation in compression and extension. We
      found that cell resistance to compression was globally higher than to extension
      regardless of the tip coating. In contrast, both tip-cell adhesion strength and
      resistance to compression and extension were the highest when probed at integrin
      specific adhesions. These integrin-specific mechanoresponses required an intact
      actin cytoskeleton, and were dependent on tyrosine phosphatases and Ca(2+)
      signaling. Cell asymmetric mechanoresponse to compression and extension remained
      after 5 minutes of tip-cell adhesion, revealing that asymmetric resistance to
      force directionality is an intrinsic property of lung cells, as in most soft
      tissues. Our findings provide new insights on how lung cells probe the
      mechanochemical properties of the microenvironment, an important process for
      migration, repair and tissue homeostasis.

PMID- 22384197
TI  - JunD/AP-1-mediated gene expression promotes lymphocyte growth dependent on
      interleukin-7 signal transduction.
AB  - Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the
      potential for promoting immune reconstitution. This feature makes IL-7 an ideal
      candidate for therapeutic development. As with other cytokines, signaling through
      the IL-7 receptor induces the JAK/STAT pathway. However, the broad scope of IL-7
      regulatory targets likely necessitates the use of other signaling components
      whose identities remain poorly defined. To this end, we used an IL-7 dependent T
      cell line to examine how expression of the glycolytic enzyme, Hexokinase II
      (HXKII) was regulated by IL-7 in a STAT5-independent manner. Our studies revealed
      that IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in
      turn, drove the expression of JunD, a component of the Activating Protein 1 (AP
      1) transcription factors. Gel shifts showed that the AP-1 complex induced by IL-7
      contained JunD but not c-Fos or c-Jun. Inhibition of JNK/JunD blocked glucose
      uptake and HXKII gene expression, indicating that this pathway was responsible
      for promoting HXKII expression. Because others had shown that JunD was a negative
      regulator of cell growth, we performed a bioinformatics analysis to uncover
      possible JunD-regulated gene targets. Our search revealed that JunD could control
      the expression of proteins involved in signal transduction, cell survival and
      metabolism. One of these growth promoters was the oncogene, Pim-1. Pim-1 is an IL
      7-induced protein that was inhibited when the activities of JNK or JunD were
      blocked, showing that in IL-7 dependent T-cells JunD can promote positive signals
      transduced through Pim-1. This was confirmed when the IL-7-induced proliferation
      of CD8 T-cells was impaired upon JunD inhibition. These results show that
      engagement of the IL-7 receptor drives a signal that is more complex than the
      JAK/STAT pathway, activating JNK and JunD to induce rapid growth stimulation
      through the expression of metabolic and signaling factors like HXKII and Pim-1.

PMID- 22384198
TI  - 17beta-Estradiol is required for the sexually dimorphic effects of repeated binge
      pattern alcohol exposure on the HPA axis during adolescence.
AB  - Alcohol consumption during adolescence has long-term sexually dimorphic effects
      on anxiety behavior and mood disorders. We have previously shown that repeated
      binge-pattern alcohol exposure increased the expression of two critical central
      regulators of stress and anxiety, corticotrophin-releasing hormone (CRH) and
      arginine vasopressin (AVP), in adolescent male rats. By contrast, there was no
      effect of alcohol on these same genes in adolescent females. Therefore, we tested
      the hypothesis that 17beta-estradiol (E(2)), the predominant sex steroid hormone
      in females, prevents alcohol-induced changes in CRH and AVP gene expression in
      the paraventricular nucleus (PVN) of the hypothalamus. To test this hypothesis,
      postnatal day (PND) 26 females were ovariectomized and given E(2) replacement or
      cholesterol as a control. Next, they were given an alcohol exposure paradigm of
      1) saline alone, 2) acute (single dose) or 3) a repeated binge-pattern. Our
      results showed that acute and repeated binge-pattern alcohol treatment increased
      plasma ACTH and CORT levels in both E(2)- and Ch-treated groups, however
      habituation to repeated binge-pattern alcohol exposure was evident only in E(2)
      treated animals. Further, repeated binge-pattern alcohol exposure significantly
      decreased CRH and AVP mRNA in Ch-, but not E(2)-treated animals, which was
      consistent with our previous observations in gonad intact females. We further
      tested the effects of E(2) and alcohol treatment on the activity of the wild type
      CRH promoter in a PVN-derived neuronal cell line. Alcohol increased CRH promoter
      activity in these cells and concomitant treatment with E(2) completely abolished
      the effect. Together our data suggest that E(2) regulates the reactivity of the
      HPA axis to a repeated stressor through modulation of the habituation response
      and further serves to maintain normal steady state mRNA levels of CRH and AVP in
      the PVN in response to a repeated alcohol stressor.

PMID- 22384199
TI  - Hemokinin-1 gene expression is upregulated in microglia activated by
      lipopolysaccharide through NF-kappaB and p38 MAPK signaling pathways.
AB  - The mammalian tachykinins, substance P (SP) and hemokinin-1 (HK-1), are widely
      distributed throughout the nervous system and/or peripheral organs, and function
      as neurotransmitters or chemical modulators by activating their cognate receptor
      NK(1). The TAC1 gene encoding SP is highly expressed in the nervous system, while
      the TAC4 gene encoding HK-1 is uniformly expressed throughout the body, including
      a variety of peripheral immune cells. Since TAC4 mRNA is also expressed in
      microglia, the resident immune cells in the central nervous system, HK-1 may be
      involved in the inflammatory processes mediated by these cells. In the present
      study, we found that TAC4, rather than TAC1, was the predominant tachykinin gene
      expressed in primary cultured microglia. TAC4 mRNA expression was upregulated in
      the microglia upon their activation by lipopolysaccharide, a well-characterized
      Toll-like receptor 4 agonist, while TAC1 mRNA expression was downregulated.
      Furthermore, both nuclear factor-kappaB and p38 mitogen-activated protein kinase
      intracellular signaling pathways were required for the upregulation of TAC4 mRNA
      expression, but not for the downregulation of TAC1 mRNA expression. These
      findings suggest that HK-1, rather than SP, plays dominant roles in the
      pathological conditions associated with microglial activation, such as
      neurodegenerative and neuroinflammatory disorders.

PMID- 22384200
TI  - A possible contribution of altered cathepsin B expression to the development of
      skin sclerosis and vasculopathy in systemic sclerosis.
AB  - Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic
      processes and extracellular matrix remodeling. While matrix metalloproteinases
      are shown to be implicated in tissue fibrosis and vasculopathy associated with
      systemic sclerosis (SSc), the role of cathepsins in this disease has not been
      well studied. The aim of this study is to evaluate the roles of CTSB in SSc.
      Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55
      SSc patients and 19 normal controls. Since the deficiency of transcription factor
      Fli1 in endothelial cells is potentially associated with the development of SSc
      vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in
      Fli1(+/-) and wild type mice as well as in SSc and control subjects. The effects
      of Fli1 gene silencing and transforming growth factor-beta (TGF-beta) on CTSB
      expression were determined by real-time PCR in human dermal microvascular
      endothelial cells (HDMECs) and dermal fibroblasts, respectively. Serum pro-CTSB
      levels were significantly higher in limited cutaneous SSc (lcSSc) and late-stage
      diffuse cutaneous SSc (dcSSc) patients than in healthy controls. In dcSSc,
      patients with increased serum pro-CTSB levels showed a significantly higher
      frequency of digital ulcers than those with normal levels. CTSB expression in
      dermal blood vessels was increased in Fli1(+/-) mice compared with wild type mice
      and in SSc patients compared with healthy controls. Consistently, Fli1 gene
      silencing increased CTSB expression in HDMECs. In cultured dermal fibroblasts
      from early dcSSc, CTSB expression was decreased compared with normal fibroblasts
      and significantly reversed by TGF-beta1 antisense oligonucleotide. In conclusion,
      up-regulation of endothelial CTSB due to Fli1 deficiency may contribute to the
      development of SSc vasculopathy, especially digital ulcers, while reduced
      expression of CTSB in lesional dermal fibroblasts is likely to be associated with
      skin sclerosis in early dcSSc.

PMID- 22384201
TI  - Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary
      Aspergillosis infection.
AB  - The recognition of pathogen-derived structures by C-type lectins and the
      chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in
      determining the host immune response to fungi. The present study was designed to
      investigate whether the presence of single nucleotide polymorphisms (SNPs) within
      DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing
      Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a
      hybrid functional/tagging approach and genotyped in 182 haematological patients,
      fifty-seven of them diagnosed with proven or probable IPA according to the 2008
      EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin
      1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G),
      DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a
      significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR =
      4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR =
      2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also
      a significantly increased frequency of galactomannan positivity among patients
      carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype.
      In addition, healthy individuals with this latter genotype showed a significantly
      decreased level of Dectin-1 mRNA expression compared to C-allele carriers,
      suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the
      levels of Dectin-1 and, consequently, the level of susceptibility to IPA
      infection. SNP-SNP interaction (epistasis) analysis revealed significant
      interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes,
      with synergistic genetic effects. Although these results need to be further
      validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2
      and CCR2 genetic variants influence the risk of IPA infection and might be useful
      in developing a risk-adapted prophylaxis.

PMID- 22384202
TI  - Contribution of transcription factor binding site motif variants to condition
      specific gene expression patterns in budding yeast.
AB  - It is now experimentally well known that variant sequences of a cis transcription
      factor binding site motif can contribute to differential regulation of genes. We
      characterize the relationship between motif variants and gene expression by
      analyzing expression microarray data and binding site predictions. To accomplish
      this, we statistically detect motif variants with effects that differ among
      environments. Such environmental specificity may be due to either affinity
      differences between variants or, more likely, differential interactions of TFs
      bound to these variants with cofactors, and with differential presence of
      cofactors across environments. We examine conservation of functional variants
      across four Saccharomyces species, and find that about a third of transcription
      factors have target genes that are differentially expressed in a condition
      specific manner that is correlated with the nucleotide at variant motif
      positions. We find good correspondence between our results and some cases in the
      experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing
      consensus in the literature indicates that motif variants may often be
      functionally distinct, that this may be observed in genomic data, and that
      variants play an important role in condition-specific gene regulation.

PMID- 22384203
TI  - MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and
      Argentina: lack of association or epistasis with IL12B polymorphisms.
AB  - The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important
      role in the recruitment of monocytes to M. tuberculosis infection sites, and
      previous studies have reported that genetic variants in MCP1 are associated with
      differential susceptibility to pulmonary tuberculosis (PTB). We examined eight
      MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control
      design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases
      and 271 controls from The Gambia, 295 cases and 179 controls from the U.S.
      (African-Americans), and an additional set of 237 cases and 144 controls of
      European ancestry from the U.S. and Argentina. Two locus interactions were also
      examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene
      implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611
      (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for
      association. One interaction between rs2857656 and IL12B SNP rs2288831 was
      observed among Africans but the effect was in the opposite direction in Guineans
      (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate
      that the effect of genetic variation within MCP1 is not clear cut and additional
      studies will be needed to elucidate its role in TB susceptibility.

PMID- 22384204
TI  - Mammalian genes preferentially co-retained in radiation hybrid panels tend to
      avoid coexpression.
AB  - Coexpression has been frequently used to explore modules of functionally related
      genes in eukaryotic genomes. However, we found that genetically interacting
      mammalian genes identified through radiation hybrid (RH) genotypes tend not to be
      coexpressed across tissues. This pattern remained unchanged after controlling for
      potential confounding factors, including chromosomal linkage, chromosomal
      distance, and gene duplication. Because >99.9% of the genetically interacting
      genes were identified according to the higher co-retention frequencies, our
      observation implies that coexpression is not necessarily an indication of the
      need for the co-presence of two genes in the genome, which is a prerequisite for
      cofunctionality of their coding proteins in the cell. Therefore, coexpression
      information must be applied cautiously to the exploration of the functional
      relatedness of genes in a genome.

PMID- 22384205
TI  - A comparison of administrative and physiologic predictive models in determining
      risk adjusted mortality rates in critically ill patients.
AB  - BACKGROUND: Hospitals are increasingly compared based on clinical outcomes
      adjusted for severity of illness. Multiple methods exist to adjust for
      differences between patients. The challenge for consumers of this information,
      both the public and healthcare providers, is interpreting differences in risk
      adjustment models particularly when models differ in their use of administrative
      and physiologic data. We set to examine how administrative and physiologic models
      compare to each when applied to critically ill patients. METHODS: We
      prospectively abstracted variables for a physiologic and administrative model of
      mortality from two intensive care units in the United States. Predicted mortality
      was compared through the Pearsons Product coefficient and Bland-Altman analysis.
      A subgroup of patients admitted directly from the emergency department was
      analyzed to remove potential confounding changes in condition prior to ICU
      admission. RESULTS: We included 556 patients from two academic medical centers in
      this analysis. The administrative model and physiologic models predicted
      mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6%
      (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r(2) for these models was
      0.297. The Bland-Atlman plot suggests that at low predicted mortality there was
      good agreement; however, as mortality increased the models diverged. Similar
      results were found when analyzing a subgroup of patients admitted directly from
      the emergency department. When comparing the two hospitals, there was a
      statistical difference when using the administrative model but not the
      physiologic model. Unexplained mortality, defined as those patients who died who
      had a predicted mortality less than 10%, was a rare event by either model.
      CONCLUSIONS: In conclusion, while it has been shown that administrative models
      provide estimates of mortality that are similar to physiologic models in non
      critically ill patients with pneumonia, our results suggest this finding can not
      be applied globally to patients admitted to intensive care units. As patients and
      providers increasingly use publicly reported information in making health care
      decisions and referrals, it is critical that the provided information be
      understood. Our results suggest that severity of illness may influence the
      mortality index in administrative models. We suggest that when interpreting
      "report cards" or metrics, health care providers determine how the risk
      adjustment was made and compares to other risk adjustment models.

PMID- 22384206
TI  - Global transcriptome profiling of the pine shoot beetle, Tomicus yunnanensis
      (Coleoptera: Scolytinae).
AB  - BACKGROUND: The pine shoot beetle Tomicus yunnanensis (Coleoptera: Scolytinae) is
      an economically important pest of Pinus yunnanensis in southwestern China.
      Developed resistance to insecticides due to chemical pesticides being used for a
      long time is a factor involved in its serious damage, which poses a challenge for
      management. In addition, highly efficient adaptation to divergent environmental
      ecologies results in this pest posing great potential threat to pine forests.
      However, the molecular mechanisms remain unknown as only limited nucleotide
      sequence data for this species is available. METHODOLOGY/PRINCIPAL FINDINGS: In
      this study, we applied next generation sequencing (Illumina sequencing) to
      sequence the adult transcriptome of T. yunnanensis. A total of 51,822,230 reads
      were obtained. They were assembled into 140,702 scaffolds, and 60,031 unigenes.
      The unigenes were further functionally annotated with gene descriptions, Gene
      Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of
      Genes and Genome (KEGG). In total, 80,932 unigenes were classified into GO,
      13,599 unigenes were assigned to COG, and 33,875 unigenes were found in KO
      categories. A biochemical pathway database containing 219 predicted pathways was
      also created based on the annotations. In depth analysis of the data revealed a
      large number of genes related to insecticides resistance and heat shock protein
      genes associated with environmental stress. CONCLUSIONS/SIGNIFICANCE: The results
      facilitate the investigations of molecular resistance mechanisms to insecticides
      and environmental stress. This study lays the foundation for future functional
      genomics studies of important biological questions of this pest.

PMID- 22384207
TI  - Brain and spinal cord interaction: protective effects of exercise prior to spinal
      cord injury.
AB  - We have investigated the effects of a spinal cord injury on the brain and spinal
      cord, and whether exercise provided before the injury could organize a protective
      reaction across the neuroaxis. Animals were exposed to 21 days of voluntary
      exercise, followed by a full spinal transection (T7-T9) and sacrificed two days
      later. Here we show that the effects of spinal cord injury go beyond the spinal
      cord itself and influence the molecular substrates of synaptic plasticity and
      learning in the brain. The injury reduced BDNF levels in the hippocampus in
      conjunction with the activated forms of p-synapsin I, p-CREB and p-CaMK II, while
      exercise prior to injury prevented these reductions. Similar effects of the
      injury were observed in the lumbar enlargement region of the spinal cord, where
      exercise prevented the reductions in BDNF, and p-CREB. Furthermore, the response
      of the hippocampus to the spinal lesion appeared to be coordinated to that of the
      spinal cord, as evidenced by corresponding injury-related changes in BDNF levels
      in the brain and spinal cord. These results provide an indication for the
      increased vulnerability of brain centers after spinal cord injury. These findings
      also imply that the level of chronic activity prior to a spinal cord injury could
      determine the level of sensory-motor and cognitive recovery following the injury.
      In particular, exercise prior to the injury onset appears to foster protective
      mechanisms in the brain and spinal cord.

PMID- 22384208
TI  - Analysis of the peptidoglycan hydrolase complement of Lactobacillus casei and
      characterization of the major gamma-D-glutamyl-L-lysyl-endopeptidase.
AB  - Peptidoglycan (PG) is the major component of Gram positive bacteria cell wall and
      is essential for bacterial integrity and shape. Bacteria synthesize PG hydrolases
      (PGHs) which are able to cleave bonds in their own PG and play major roles in PG
      remodelling required for bacterial growth and division. Our aim was to identify
      the main PGHs in Lactobacillus casei BL23, a lactic acid bacterium with probiotic
      properties.The PGH complement was first identified in silico by amino acid
      sequence similarity searches of the BL23 genome sequence. Thirteen PGHs were
      detected with different predicted hydrolytic specificities. Transcription of the
      genes was confirmed by RT-PCR. A proteomic analysis combining the use of SDS-PAGE
      and LC-MS/MS revealed the main seven PGHs synthesized during growth of L. casei
      BL23. Among these PGHs, LCABL_02770 (renamed Lc-p75) was identified as the major
      one. This protein is the homolog of p75 (Msp1) major secreted protein of
      Lactobacillus rhamnosus GG, which was shown to promote survival and growth of
      intestinal epithelial cells. We identified its hydrolytic specificity on PG and
      showed that it is a gamma-D-glutamyl-L-lysyl-endopeptidase. It has a marked
      specificity towards PG tetrapeptide chains versus tripeptide chains and for
      oligomers rather than monomers. Immunofluorescence experiments demonstrated that
      Lc-p75 localizes at cell septa in agreement with its role in daughter cell
      separation. It is also secreted under an active form as detected in zymogram.
      Comparison of the muropeptide profiles of wild type and Lc-p75-negative mutant
      revealed a decrease of the amount of disaccharide-dipeptide in the mutant PG in
      agreement with Lc-p75 activity. As a conclusion, Lc-p75 is the major L. casei
      BL23 PGH with endopeptidase specificity and a key role in daughter cell
      separation. Further studies will aim at investigating the role of Lc-p75 in the
      anti-inflammatory potential of L. casei BL23.

PMID- 22384209
TI  - The TAL effector PthA4 interacts with nuclear factors involved in RNA-dependent
      processes including a HMG protein that selectively binds poly(U) RNA.
AB  - Plant pathogenic bacteria utilize an array of effector proteins to cause disease.
      Among them, transcriptional activator-like (TAL) effectors are unusual in the
      sense that they modulate transcription in the host. Although target genes and DNA
      specificity of TAL effectors have been elucidated, how TAL proteins control host
      transcription is poorly understood. Previously, we showed that the Xanthomonas
      citri TAL effectors, PthAs 2 and 3, preferentially targeted a citrus protein
      complex associated with transcription control and DNA repair. To extend our
      knowledge on the mode of action of PthAs, we have identified new protein targets
      of the PthA4 variant, required to elicit canker on citrus. Here we show that all
      the PthA4-interacting proteins are DNA and/or RNA-binding factors implicated in
      chromatin remodeling and repair, gene regulation and mRNA
      stabilization/modification. The majority of these proteins, including a
      structural maintenance of chromosomes protein (CsSMC), a translin-associated
      factor X (CsTRAX), a VirE2-interacting protein (CsVIP2), a high mobility group
      (CsHMG) and two poly(A)-binding proteins (CsPABP1 and 2), interacted with each
      other, suggesting that they assemble into a multiprotein complex. CsHMG was shown
      to bind DNA and to interact with the invariable leucine-rich repeat region of
      PthAs. Surprisingly, both CsHMG and PthA4 interacted with PABP1 and 2 and showed
      selective binding to poly(U) RNA, a property that is novel among HMGs and TAL
      effectors. Given that homologs of CsHMG, CsPABP1, CsPABP2, CsSMC and CsTRAX in
      other organisms assemble into protein complexes to regulate mRNA stability and
      translation, we suggest a novel role of TAL effectors in mRNA processing and
      translational control.

PMID- 22384210
TI  - Combined chromatin and expression analysis reveals specific regulatory mechanisms
      within cytokine genes in the macrophage early immune response.
AB  - Macrophages play a critical role in innate immunity, and the expression of early
      response genes orchestrate much of the initial response of the immune system.
      Macrophages undergo extensive transcriptional reprogramming in response to
      inflammatory stimuli such as Lipopolysaccharide (LPS).To identify gene
      transcription regulation patterns involved in early innate immune responses, we
      used two genome-wide approaches--gene expression profiling and chromatin
      immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2
      hrs LPS stimulation on early gene expression and its relation to chromatin
      remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase
      II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional
      initiation. Our results indicate novel and alternative gene regulatory mechanisms
      for certain proinflammatory genes. We identified two groups of up-regulated
      inflammatory genes with respect to chromatin modification and promoter features.
      One group, including highly up-regulated genes such as tumor necrosis factor
      (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The
      second group, containing inflammatory mediators (interleukins and CCL
      chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their
      annotated promoters, which were low in CpG content but did contain TATA boxes.
      Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS
      condition. However, within these, an unpacking/expansion of already existing H3Ac
      peaks was observed upon LPS stimulation. In contrast, a significant proportion of
      S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data
      indicated a large portion of previously unannotated TSSs, particularly in LPS
      stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap
      annotated promoters. The regulation of the inflammatory response appears to occur
      in a very specific manner at the chromatin level for specific genes and this
      study highlights the level of fine-tuning that occurs in the immune response.

PMID- 22384211
TI  - Behavioral impact of unisensory and multisensory audio-tactile events: pros and
      cons for interlimb coordination in juggling.
AB  - Recent behavioral neuroscience research revealed that elementary reactive
      behavior can be improved in the case of cross-modal sensory interactions thanks
      to underlying multisensory integration mechanisms. Can this benefit be
      generalized to an ongoing coordination of movements under severe physical
      constraints? We choose a juggling task to examine this question. A central issue
      well-known in juggling lies in establishing and maintaining a specific temporal
      coordination among balls, hands, eyes and posture. Here, we tested whether
      providing additional timing information about the balls and hands motions by
      using external sound and tactile periodic stimulations, the later presented at
      the wrists, improved the behavior of jugglers. One specific combination of
      auditory and tactile metronome led to a decrease of the spatiotemporal
      variability of the juggler's performance: a simple sound associated to left and
      right tactile cues presented antiphase to each other, which corresponded to the
      temporal pattern of hands movement in the juggling task. A contrario, no
      improvements were obtained in the case of other auditory and tactile
      combinations. We even found a degraded performance when tactile events were
      presented alone. The nervous system thus appears able to integrate in efficient
      way environmental information brought by different sensory modalities, but only
      if the information specified matches specific features of the coordination
      pattern. We discuss the possible implications of these results for the
      understanding of the neuronal integration process implied in audio-tactile
      interaction in the context of complex voluntary movement, and considering the
      well-known gating effect of movement on vibrotactile perception.

PMID- 22384212
TI  - Pivotal role of inosine triphosphate pyrophosphatase in maintaining genome
      stability and the prevention of apoptosis in human cells.
AB  - Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA
      replication and the suppression of mutagenesis and carcinogenesis. ITPases are
      nucleoside triphosphate pyrophosphatases that clean the precursor pools of the
      non-canonical triphosphates of inosine and xanthine. The precise role of the
      human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is
      clinically important because a widespread polymorphism, 94C>A, leads to null
      ITPase activity in erythrocytes and is associated with an adverse reaction to
      thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using
      the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a
      substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes
      HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage
      and cytotoxicity observed in ITPA knockdown cells are rescued by an
      overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that
      ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our
      studies reveal the significance of ITPA in preventing base analog-induced
      apoptosis, DNA damage and mutagenesis in human cells. This implies that
      individuals with defective ITPase are predisposed to genome damage by impurities
      in nucleotide pools, which is drastically augmented by therapy with purine
      analogs. They are also at an elevated risk for degenerative diseases and cancer.

PMID- 22384213
TI  - Genetic variability in beta-defensins is not associated with susceptibility to
      Staphylococcus aureus bacteremia.
AB  - INTRODUCTION: Human beta-defensins are key components of human innate immunity to
      a variety of pathogens, including Staphylococcus aureus. The aim of the present
      study was to investigate a potential association between gene variations in DEFB1
      and DEFB103/DEFB4 and the development of S. aureus bacteremia (SAB) employing a
      case-control design. METHODS: Cases were unique patients with documented SAB,
      identified with the National S. aureus Bacteremia Register, a comprehensive
      dataset of all episodes of community associated-SABs (CA-SAB) occurring in
      children (<=20 yrs) in Denmark from 1990 to 2006. Controls were age-matched
      healthy individuals with no history of SAB. DNA obtained from cases and controls
      using the Danish Newborn Screening Biobank were genotyped for functional
      polymorphisms of DEFB1 by Sanger sequencing and copy number variation of the
      DEFB103 and DEFB4 genes using Pyrosequencing-based Paralogue Ratio Test (P-PRT).
      RESULTS: 193 ethnic Danish SAB cases with 382 age-matched controls were used for
      this study. S. aureus isolates represented a variety of bacterial (i.e.,
      different spa types) types similar to SAB isolates in general. DEFB1 minor allele
      frequencies of rs11362 (cases vs. controls 0.47/0.44), rs1800972 (0.21/0.24), and
      rs1799946 (0.32/0.33) were not significantly different in cases compared with
      controls. Also, DEFB4/DEFB103 gene copy numbers (means 4.83/4.92) were not
      significantly different in cases compared with controls. CONCLUSIONS: Using a
      large, unique cohort of pediatric CA-SAB, we found no significant association
      between DEFB1 genetic variation or DEFB4/DEFB103 gene copy number and
      susceptibility for SAB.

PMID- 22384214
TI  - Mutation of pescadillo disrupts oligodendrocyte formation in zebrafish.
AB  - BACKGROUND: In vertebrates, the myelin sheath is essential for efficient
      propagation of action potentials along the axon shaft. Oligodendrocytes are the
      cells of the central nervous system that create myelin sheaths. During
      embryogenesis, ventral neural tube precursors give rise to oligodendrocyte
      progenitor cells, which divide and migrate throughout the central nervous system.
      This study aimed to investigate mechanisms that regulate oligodendrocyte
      progenitor cell formation. METHODOLOGY/PRINCIPAL FINDINGS: By conducting a
      mutagenesis screen in transgenic zebrafish, we identified a mutation, designated
      vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells
      in the dorsal spinal cord. We subsequently determined that vu166 is an allele of
      pescadillo, a gene known to play a role in ribosome biogenesis and cell
      proliferation. We found that pescadillo function is required for both the proper
      number of oligodendrocyte progenitors to form, by regulating cell cycle
      progression, and for normal levels of myelin gene expression.
      CONCLUSIONS/SIGNIFICANCE: Our data provide evidence that neural precursors
      require pes function to progress through the cell cycle and produce
      oligodendrocyte progenitor cells and for oligodendrocyte differentiation.

PMID- 22384215
TI  - Disentangling the intertwined genetic bases of root and shoot growth in
      Arabidopsis.
AB  - Root growth and architecture are major components of plant nutrient and water use
      efficiencies and these traits are the matter of extensive genetic analysis in
      several crop species. Because root growth relies on exported assimilate from the
      shoot, and changes in assimilate supply are known to alter root architecture, we
      hypothesized (i) that the genetic bases of root growth could be intertwined with
      the genetic bases of shoot growth and (ii) that the link could be either
      positive, with alleles favouring shoot growth also favouring root growth, or
      negative, because of competition for assimilates. We tested these hypotheses
      using a quantitative genetics approach in the model species Arabidopsis thaliana
      and the Bay-0 * Shahdara recombinant inbred lines population. In accordance with
      our hypothesis, root and shoot growth traits were strongly correlated and most
      root growth quantitative trait loci (QTLs) colocalized with shoot growth QTLs
      with positive alleles originating from either the same or the opposite parent. In
      order to identify regions that could be responsible for root growth independently
      of the shoot, we generated new variables either based on root to shoot ratios,
      residuals of root to shoot correlations or coordinates of principal component
      analysis. These variables showed high heritability allowing genetic analysis.
      They essentially all yielded similar results pointing towards two regions
      involved in the root--shoot balance. Using Heterogeneous Inbred Families (a kind
      of near-isogenic lines), we validated part of the QTLs present in these two
      regions for different traits. Our study thus highlights the difficulty of
      disentangling intertwined genetic bases of root and shoot growth and shows that
      this difficulty can be overcome by using simple statistical tools.

PMID- 22384216
TI  - Phenotypic plasticity influences the size, shape and dynamics of the geographic
      distribution of an invasive plant.
AB  - Phenotypic plasticity has long been suspected to allow invasive species to expand
      their geographic range across large-scale environmental gradients. We tested this
      possibility in Australia using a continental scale survey of the invasive tree
      Parkinsonia aculeata (Fabaceae) in twenty-three sites distributed across four
      climate regions and three habitat types. Using tree-level responses, we detected
      a trade-off between seed mass and seed number across the moisture gradient.
      Individual trees plastically and reversibly produced many small seeds at dry
      sites or years, and few big seeds at wet sites and years. Bigger seeds were
      positively correlated with higher seed and seedling survival rates. The trade
      off, the relation between seed mass, seed and seedling survival, and other
      fitness components of the plant life-cycle were integrated within a matrix
      population model. The model confirms that the plastic response resulted in
      average fitness benefits across the life-cycle. Plasticity resulted in average
      fitness being positively maintained at the wet and dry range margins where
      extinction risks would otherwise have been high ("Jack-of-all-Trades" strategy
      JT), and fitness being maximized at the species range centre where extinction
      risks were already low ("Master-of-Some" strategy MS). The resulting hybrid "Jack
      and-Master" strategy (JM) broadened the geographic range and amplified average
      fitness in the range centre. Our study provides the first empirical evidence for
      a JM species. It also confirms mechanistically the importance of phenotypic
      plasticity in determining the size, the shape and the dynamic of a species
      distribution. The JM allows rapid and reversible phenotypic responses to new or
      changing moisture conditions at different scales, providing the species with
      definite advantages over genetic adaptation when invading diverse and variable
      environments. Furthermore, natural selection pressure acting on phenotypic
      plasticity is predicted to result in maintenance of the JT and strengthening of
      the MS, further enhancing the species invasiveness in its range centre.

PMID- 22384217
TI  - Longitudinal tracking of human fetal cells labeled with super paramagnetic iron
      oxide nanoparticles in the brain of mice with motor neuron disease.
AB  - Stem Cell (SC) therapy is one of the most promising approaches for the treatment
      of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron
      Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells
      (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine
      model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we
      found that: 1) the main physical parameters of SPIOn were maintained over time;
      2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258
      labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle,
      proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs
      rapidly spread to the whole ventricular system, but did not migrate into the
      brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both
      wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not
      influence mice survival.

PMID- 22384218
TI  - Acute kidney injury biomarkers for patients in a coronary care unit: a
      prospective cohort study.
AB  - BACKGROUND: Renal dysfunction is an established predictor of all-cause mortality
      in intensive care units. This study analyzed the outcomes of coronary care unit
      (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI),
      including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL
      18) and cystatin C (CysC) on the first day of CCU admission.
      METHODOLOGY/PRINCIPAL FINDINGS: Serum and urinary samples collected from 150
      patients in the coronary care unit of a tertiary care university hospital between
      September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective
      demographic, clinical and laboratory data were evaluated as predictors of
      survival in this patient group. The most common cause of CCU admission was acute
      myocardial infarction (80%). According to Acute Kidney Injury Network criteria,
      28.7% (43/150) of CCU patients had AKI of varying severity. Cumulative survival
      rates at 6-month follow-up following hospital discharge differed significantly
      (p<0.05) between patients with AKI versus those without AKI. For predicting AKI,
      serum CysC displayed an excellent areas under the receiver operating
      characteristic curve (AUROC) (0.895 +/- 0.031, p < 0.001). The overall 180-day
      survival rate was 88.7% (133/150). Multiple Cox logistic regression hazard
      analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and
      Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were
      independent risk factors for 6-month mortality. In terms of 6-month mortality,
      urinary NGAL had the best discriminatory power, the best Youden index, and the
      highest overall correctness of prediction. CONCLUSIONS: Our data showed that
      serum CysC has the best discriminative power for predicting AKI in CCU patients.
      However, urinary NGAL and serum IL-18 are associated with short-term mortality in
      these critically ill patients.

PMID- 22384219
TI  - Macrophage sub-populations and the lipoxin A4 receptor implicate active
      inflammation during equine tendon repair.
AB  - Macrophages (Mphi) orchestrate inflammatory and reparatory processes in injured
      connective tissues but their role during different phases of tendon healing is
      not known. We investigated the contribution of different Mphi subsets in an
      equine model of naturally occurring tendon injury. Post mortem tissues were
      harvested from normal (uninjured), sub-acute (3-6 weeks post injury) and
      chronically injured (>3 months post injury) superficial digital flexor tendons.
      To determine if inflammation was present in injured tendons, Mphi sub-populations
      were quantified based on surface antigen expression of CD172a (pan Mphi),
      CD14(high)CD206(low) (pro-inflammatory M1Mphi), and CD206(high) (anti
      inflammatory M2Mphi) to assess potential polarised phenotypes. In addition, the
      Lipoxin A(4) receptor (FPR2/ALX) was used as marker for resolving inflammation.
      Normal tendons were negative for both Mphi and FPR2/ALX. In contrast, M1Mphi
      predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mphi
      polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by
      tenocytes was significantly upregulated in sub-acute but not chronic injury.
      Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in
      sub-acute and chronic injuries in contrast to low level expression in normal
      tendons. The combination of reduced FPR2/ALX expression and persistence of the
      M2Mphi phenotype in chronic injury suggests a potential mechanism for incomplete
      resolution of inflammation after tendon injury. To investigate the effect of pro
      inflammatory mediators on lipoxin A(4) (LXA(4)) production and FPR2/ALX
      expression in vitro, normal tendon explants were stimulated with interleukin-1
      beta and prostaglandin E(2). Stimulation with either mediator induced LXA(4)
      release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken
      together, our data suggests that although tenocytes are capable of mounting a
      protective mechanism to counteract inflammatory stimuli, this appears to be of
      insufficient duration and magnitude in natural tendon injury, which may
      potentiate chronic inflammation and fibrotic repair, as indicated by the presence
      of M2Mphi.

PMID- 22384220
TI  - How stress alters memory in 'smart' snails.
AB  - Cognitive ability varies within species, but whether this variation alters the
      manner in which memory formation is affected by environmental stress is unclear.
      The great pond snail, Lymnaea stagnalis, is commonly used as model species in
      studies of learning and memory. The majority of those studies used a single
      laboratory strain (i.e. the Dutch strain) originating from a wild population in
      the Netherlands. However, our recent work has identified natural populations that
      demonstrate significantly enhanced long-term memory (LTM) formation relative to
      the Dutch strain following operant conditioning of aerial respiratory behaviour.
      Here we assess how two populations with enhanced memory formation (i.e. 'smart'
      snails), one from Canada (Trans Canada 1: TC1) and one from the U.K. (Chilton
      Moor: CM) respond to ecologically relevant stressors. In control conditions the
      Dutch strain forms memory lasting 1-3 h following a single 0.5 h training session
      in our standard calcium pond water (80 mg/l [Ca(2+)]), whereas the TC1 and CM
      populations formed LTM lasting 5+ days following this training regime. Exposure
      to low environmental calcium pond water (20 mg/l [Ca(2+)]), which blocks LTM in
      the Dutch strain, reduced LTM retention to 24 h in the TC1 and CM populations.
      Crowding (20 snails in 100 ml) immediately prior to training blocks LTM in the
      Dutch strain, and also did so in TC1 and CM populations. Therefore, snails with
      enhanced cognitive ability respond to these ecologically relevant stressors in a
      similar manner to the Dutch strain, but are more robust at forming LTM in a low
      calcium environment. Despite the two populations (CM and TC1) originating from
      different continents, LTM formation was indistinguishable in both control and
      stressed conditions. This indicates that the underlying mechanisms controlling
      cognitive differences among populations may be highly conserved in L. stagnalis.

PMID- 22384221
TI  - Characterization of genome-wide association-identified variants for atrial
      fibrillation in African Americans.
AB  - BACKGROUND: Despite a greater burden of risk factors, atrial fibrillation (AF) is
      less common among African Americans than European-descent populations. Genome
      wide association studies (GWAS) for AF in European-descent populations have
      identified three predominant genomic regions associated with increased risk
      (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African
      American is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We studied 73 African
      Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American
      controls, with no history of AF including after cardiac surgery. Tests of
      association were performed for 148 SNPs across the three regions associated with
      AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the
      strongest associations in African Americans were both different from the index
      SNPs identified in European-descent populations and independent from the index
      European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds
      ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25
      rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1,
      95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among
      cases (23.6%) and controls (23.8%). Accordingly, the probability of having two
      copies of the European derived chromosomes at each region did not differ between
      cases and controls. CONCLUSIONS/SIGNIFICANCE: Variable European admixture at
      known AF loci does not explain decreased AF susceptibility in African Americans.
      These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for
      African Americans, although the index SNPs differ from those identified in
      European-descent populations.

PMID- 22384222
TI  - Historical legacies in world amphibian diversity revealed by the turnover and
      nestedness components of Beta diversity.
AB  - Historic processes are expected to influence present diversity patterns in
      combination with contemporary environmental factors. We hypothesise that the
      joint use of beta diversity partitioning methods and a threshold-based approach
      may help reveal the effect of large-scale historic processes on present
      biodiversity. We partitioned intra-regional beta diversity into its turnover
      (differences in composition caused by species replacements) and nestedness
      resultant (differences in species composition caused by species losses)
      components. We used piecewise regressions to show that, for amphibian beta
      diversity, two different world regions can be distinguished. Below parallel 37,
      beta diversity is dominated by turnover, while above parallel 37, beta diversity
      is dominated by nestedness. Notably, these regions are revealed when the
      piecewise regression method is applied to the relationship between latitude and
      the difference between the Last Glacial Maximum (LGM) and the present temperature
      but not when present energy-water factors are analysed. When this threshold
      effect of historic climatic change is partialled out, current energy-water
      variables become more relevant to the nestedness-resultant dissimilarity
      patterns, while mountainous areas are associated with higher spatial turnover.
      This result suggests that nested patterns are caused by species losses that are
      determined by physiological constraints, whereas turnover is associated with
      speciation and/or Pleistocene refugia. Thus, the new threshold-based view may
      help reveal the role of historic factors in shaping present amphibian beta
      diversity patterns.

PMID- 22384223
TI  - In vivo diagnostic imaging using micro-CT: sequential and comparative evaluation
      of rodent models for hepatic/brain ischemia and stroke.
AB  - BACKGROUND: There is an increasing need for animal disease models for
      pathophysiological research and efficient drug screening. However, one of the
      technical barriers to the effective use of the models is the difficulty of non
      invasive and sequential monitoring of the same animals. Micro-CT is a powerful
      tool for serial diagnostic imaging of animal models. However, soft tissue
      contrast resolution, particularly in the brain, is insufficient for detailed
      analysis, unlike the current applications of CT in the clinical arena. We address
      the soft tissue contrast resolution issue in this report. METHODOLOGY: We
      performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral
      infarction and hepatic ischemia. Pathological changes in each lesion were
      quantified for two weeks by measuring the lesion volume or the ratio of high
      attenuation area (%HAA), indicative of increased vascular permeability. We also
      compared brain images of stroke rats and ischemic mice acquired with micro-CT to
      those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to
      confirm the diagnosis by CECT. PRINCIPAL FINDINGS: In the models of cerebral
      infarction, vascular permeability was increased from three days through one week
      after surgical initiation, which was also confirmed by Evans blue dye leakage.
      Measurement of volume and %HAA of the liver lesions demonstrated differences in
      the recovery process between mice with distinct genetic backgrounds. Comparison
      of CT and MR images acquired from the same stroke rats or ischemic mice indicated
      that accuracy of volumetric measurement, as well as spatial and contrast
      resolutions of CT images, was comparable to that obtained with MRI. The imaging
      results were also consistent with the histological data. CONCLUSIONS: This study
      demonstrates that the CECT scanning method is useful in rodents for both
      quantitative and qualitative evaluations of pathologic lesions in tissues/organs
      including the brain, and is also suitable for longitudinal observation of the
      same animals.

PMID- 22384224
TI  - Active site mutations change the cleavage specificity of neprilysin.
AB  - Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent
      endopeptidase family is a membrane bound peptidase capable of cleaving a variety
      of physiological peptides. We have generated a series of neprilysin variants
      containing mutations at either one of two active site residues, Phe(563) and
      Ser(546). Among the mutants studied in detail we observed changes in their
      activity towards leucine(5)-enkephalin, insulin B chain, and amyloid beta(1-40).
      For example, NEP(F563I) displayed an increase in preference towards cleaving
      leucine(5)-enkephalin relative to insulin B chain, while mutant NEP(S546E) was
      less discriminating than neprilysin. Mutants NEP(F563L) and NEP(S546E) exhibit
      different cleavage site preferences than neprilysin with insulin B chain and
      amyloid beta(1-40) as substrates. These data indicate that it is possible to
      alter the cleavage site specificity of neprilysin opening the way for the
      development of substrate specific or substrate exclusive forms of the enzyme with
      enhanced therapeutic potential.

PMID- 22384225
TI  - Cytokine signaling in splenic leukocytes from vaccinated and non-vaccinated
      chickens after intravenous infection with Salmonella enteritidis.
AB  - In order to design a new Salmonella enterica vaccine, one needs to understand how
      naive and immune chickens interact differently when exposed to S. enterica. In
      this study we therefore determined the immune response of vaccinated and non
      vaccinated chickens after intravenous infection with Salmonella enterica serovar
      Enteritidis (S. Enteritidis). Using flow cytometry we showed that 4 days post
      infection (DPI), counts of CD4 and B-lymphocytes did not change, CD8 and
      gammadelta T-lymphocytes decreased and macrophages and heterophils increased in
      the spleen. When vaccinated and non-vaccinated chickens were compared, only
      macrophages and heterophils were found in significantly higher counts in the
      spleens of the non-vaccinated chickens. The non-vaccinated chickens also
      expressed higher anti-LPS antibodies than the vaccinated chickens. The expression
      of interleukin (IL)1beta, IL6, IL8, IL18, LITAF, IFNgamma and iNOS did not
      exhibit any clear pattern in the cells sorted from the spleens of vaccinated or
      non-vaccinated chickens. Only IL17 and IL22 showed a differential expression in
      the CD4 T-lymphocytes of the vaccinated and non-vaccinated chickens at 4 DPI,
      both being expressed at a higher level in the non-vaccinated chickens. Due to a
      similar IFNgamma expression in the CD4 T-lymphocytes in both the vaccinated and
      non-vaccinated chickens, and a variable IL17 expression oscillating around
      IFNgamma expression levels, the IL17?IFNgamma ratio in CD4 T-lymphocytes was
      found to be central for the outcome of the immune response. When IL17 was
      expressed at higher levels than IFNgamma in the non-vaccinated chickens, the Th17
      immune response with a higher macrophage and heterophil infiltration in the
      spleen dominated. However, when the expression of IL17 was lower than that of
      IFNgamma as in the vaccinated chickens, the Th1 response with a higher resistance
      to S. Enteritidis infection dominated.

PMID- 22384226
TI  - Characterization of Pax2 expression in the goldfish optic nerve head during
      retina regeneration.
AB  - The Pax2 transcription factor plays a crucial role in axon-guidance and astrocyte
      differentiation in the optic nerve head (ONH) during vertebrate visual system
      development. However, little is known about its function during regeneration. The
      fish visual system is in continuous growth and can regenerate. Muller cells and
      astrocytes of the retina and ONH play an important role in these processes. We
      demonstrate that pax2a in goldfish is highly conserved and at least two pax2a
      transcripts are expressed in the optic nerve. Moreover, we show two different
      astrocyte populations in goldfish: Pax2(+) astrocytes located in the ONH and
      S100(+) astrocytes distributed throughout the retina and the ONH. After
      peripheral growth zone (PGZ) cryolesion, both Pax2(+) and S100(+) astrocytes have
      different responses. At 7 days after injury the number of Pax2(+) cells is
      reduced and coincides with the absence of young axons. In contrast, there is an
      increase of S100(+) astrocytes in the retina surrounding the ONH and S100(+)
      processes in the ONH. At 15 days post injury, the PGZ starts to regenerate and
      the number of S100(+) astrocytes increases in this region. Moreover, the
      regenerating axons reach the ONH and the pax2a gene expression levels and the
      number of Pax2(+) cells increase. At the same time, S100(+)/GFAP(+)/GS(+)
      astrocytes located in the posterior ONH react strongly. In the course of the
      regeneration, Muller cell vitreal processes surrounding the ONH are primarily
      disorganized and later increase in number. During the whole regenerative process
      we detect a source of Pax2(+)/PCNA(+) astrocytes surrounding the posterior ONH.
      We demonstrate that pax2a expression and the Pax2(+) astrocyte population in the
      ONH are modified during the PGZ regeneration, suggesting that they could play an
      important role in this process.

PMID- 22384227
TI  - The complete mitochondrial genomes of six heterodont bivalves (Tellinoidea and
      Solenoidea): variable gene arrangements and phylogenetic implications.
AB  - BACKGROUND: Taxonomy and phylogeny of subclass Heterodonta including Tellinoidea
      are long-debated issues and a complete agreement has not been reached yet.
      Mitochondrial (mt) genomes have been proved to be a powerful tool in resolving
      phylogenetic relationship. However, to date, only ten complete mitochondrial
      genomes of Heterodonta, which is by far the most diverse major group of Bivalvia,
      have been determined. In this paper, we newly sequenced the complete mt genomes
      of six species belonging to Heterodonta in order to resolve some problematical
      relationships among this subclass. PRINCIPAL FINDINGS: The complete mt genomes of
      six species vary in size from 16,352 bp to 18,182. Hairpin-like secondary
      structures are found in the largest non-coding regions of six freshly sequenced
      mt genomes, five of which contain tandem repeats. It is noteworthy that two
      species belonging to the same genus show different gene arrangements with three
      translocations. The phylogenetic analysis of Heterodonta indicates that
      Sinonovacula constricta, distant from the Solecurtidae belonging to Tellinoidea,
      is as a sister group with Solen grandis of family Solenidae. Besides, all five
      species of Tellinoidea cluster together, while Sanguinolaria diphos has closer
      relationship with Solecurtus divaricatus, Moerella iridescens and Semele scaba
      rather than with Sanguinolaria olivacea. CONCLUSIONS/SIGNIFICANCE: By comparative
      study of gene order rearrangements and phylogenetic relationships of the five
      species belonging to Tellinoidea, our results support that comparisons of mt gene
      order rearrangements, to some extent, are a useful tool for phylogenetic studies.
      Based on phylogenetic analyses of multiple protein-coding genes, we prefer
      classifying the genus Sinonovacula within the superfamily Solenoidea and not the
      superfamily Tellinoidea. Besides, both gene order and sequence data agree that
      Sanguinolaria (Psammobiidae) is not monophyletic. Nevertheless, more studies
      based on more mt genomes via combination of gene order and phylogenetic analysis
      are needed to further understand the phylogenetic relationships in subclass
      Heterodonta.

PMID- 22384228
TI  - Gene expression analyses of subchondral bone in early experimental osteoarthritis
      by microarray.
AB  - Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage
      and bone. A better understanding of the early molecular changes in subchondral
      bone may help elucidate the pathogenesis of OA. We used microarray technology to
      investigate the time course of molecular changes in the subchondral bone in the
      early stages of experimental osteoarthritis in a rat model. We identified 2,234
      differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4
      weeks post-surgery. Further analyses of the dysregulated genes indicated that the
      events underlying subchondral bone remodeling occurred sequentially and in a time
      dependent manner at the gene expression level. Some of the identified
      dysregulated genes that were identified have suspected roles in bone development
      or remodeling; these genes include Alp, Igf1, Tgf beta1, Postn, Mmp3, Tnfsf11,
      Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were
      confirmed by real-time PCR, and the results indicated that our microarray data
      accurately reflected gene expression patterns characteristic of early OA. To
      validate the results of our microarray analysis at the protein level,
      immunohistochemistry staining was used to investigate the expression of Mmp3 and
      Aspn protein in tissue sections. These analyses indicate that Mmp3 protein
      expression completely matched the results of both the microarray and real-time
      PCR analyses; however, Aspn protein expression was not observed to differ at any
      time. In summary, our study demonstrated a simple method of separation of
      subchondral bone sample from the knee joint of rat, which can effectively avoid
      bone RNA degradation. These findings also revealed the gene expression profiles
      of subchondral bone in the rat OA model at multiple time points post-surgery and
      identified important DE genes with known or suspected roles in bone development
      or remodeling. These genes may be novel diagnostic markers or therapeutic targets
      for OA.

PMID- 22384229
TI  - How can selection of biologically inspired features improve the performance of a
      robust object recognition model?
AB  - Humans can effectively and swiftly recognize objects in complex natural scenes.
      This outstanding ability has motivated many computational object recognition
      models. Most of these models try to emulate the behavior of this remarkable
      system. The human visual system hierarchically recognizes objects in several
      processing stages. Along these stages a set of features with increasing
      complexity is extracted by different parts of visual system. Elementary features
      like bars and edges are processed in earlier levels of visual pathway and as far
      as one goes upper in this pathway more complex features will be spotted. It is an
      important interrogation in the field of visual processing to see which features
      of an object are selected and represented by the visual cortex. To address this
      issue, we extended a hierarchical model, which is motivated by biology, for
      different object recognition tasks. In this model, a set of object parts, named
      patches, extracted in the intermediate stages. These object parts are used for
      training procedure in the model and have an important role in object recognition.
      These patches are selected indiscriminately from different positions of an image
      and this can lead to the extraction of non-discriminating patches which
      eventually may reduce the performance. In the proposed model we used an
      evolutionary algorithm approach to select a set of informative patches. Our
      reported results indicate that these patches are more informative than usual
      random patches. We demonstrate the strength of the proposed model on a range of
      object recognition tasks. The proposed model outperforms the original model in
      diverse object recognition tasks. It can be seen from the experiments that
      selected features are generally particular parts of target images. Our results
      suggest that selected features which are parts of target objects provide an
      efficient set for robust object recognition.

PMID- 22384230
TI  - Comparison of tobacco control scenarios: quantifying estimates of long-term
      health impact using the DYNAMO-HIA modeling tool.
AB  - BACKGROUND: There are several types of tobacco control interventions/policies
      which can change future smoking exposure. The most basic intervention types are
      1) smoking cessation interventions 2) preventing smoking initiation and 3)
      implementation of a nationwide policy affecting quitters and starters
      simultaneously. The possibility for dynamic quantification of such different
      interventions is key for comparing the timing and size of their effects. METHODS
      AND RESULTS: We developed a software tool, DYNAMO-HIA, which allows for a
      quantitative comparison of the health impact of different policy scenarios. We
      illustrate the outcomes of the tool for the three typical types of tobacco
      control interventions if these were applied in the Netherlands. The tool was used
      to model the effects of different types of smoking interventions on future
      smoking prevalence and on health outcomes, comparing these three scenarios with
      the business-as-usual scenario. The necessary data input was obtained from the
      DYNAMO-HIA database which was assembled as part of this project. All smoking
      interventions will be effective in the long run. The population-wide strategy
      will be most effective in both the short and long term. The smoking cessation
      scenario will be second-most effective in the short run, though in the long run
      the smoking initiation scenario will become almost as effective. Interventions
      aimed at preventing the initiation of smoking need a long time horizon to become
      manifest in terms of health effects. The outcomes strongly depend on the groups
      targeted by the intervention. CONCLUSION: We calculated how much more effective
      the population-wide strategy is, in both the short and long term, compared to
      quit smoking interventions and measures aimed at preventing the initiation of
      smoking. By allowing a great variety of user-specified choices, the DYNAMO-HIA
      tool is a powerful instrument by which the consequences of different tobacco
      control policies and interventions can be assessed.

PMID- 22384231
TI  - Access to reliable information about long-term prognosis influences clinical
      opinion on use of lifesaving intervention.
AB  - BACKGROUND: Decompressive craniectomy has been traditionally used as a lifesaving
      rescue treatment in severe traumatic brain injury (TBI). This study assessed
      whether objective information on long-term prognosis would influence healthcare
      workers' opinion about using decompressive craniectomy as a lifesaving procedure
      for patients with severe TBI. METHOD: A two-part structured interview was used to
      assess the participants' opinion to perform decompressive craniectomy for three
      patients who had very severe TBI. Their opinion was assessed before and after
      knowing the predicted and observed risks of an unfavourable long-term
      neurological outcome in various scenarios. RESULTS: Five hundred healthcare
      workers with a wide variety of clinical backgrounds participated. The
      participants were significantly more likely to recommend decompressive
      craniectomy for their patients than for themselves (mean difference in visual
      analogue scale [VAS] -1.5, 95% confidence interval -1.3 to -1.6), especially when
      the next of kin of the patients requested intervention. Patients' preferences
      were more similar to patients who had advance directives. The participants'
      preferences to perform the procedure for themselves and their patients both
      significantly reduced after knowing the predicted risks of unfavourable outcomes,
      and the changes in attitude were consistent across different specialties, amount
      of experience in caring for similar patients, religious backgrounds, and
      positions in the specialty of the participants. CONCLUSIONS: Access to objective
      information on risk of an unfavourable long-term outcome influenced healthcare
      workers' decision to recommend decompressive craniectomy, considered as a
      lifesaving procedure, for patients with very severe TBI.

PMID- 22384232
TI  - Spleen tyrosine kinase regulates AP-1 dependent transcriptional response to
      minimally oxidized LDL.
AB  - Oxidative modification of low-density lipoprotein (LDL) turns it into an
      endogenous ligand recognized by pattern-recognition receptors. We have
      demonstrated that minimally oxidized LDL (mmLDL) binds to CD14 and mediates
      TLR4/MD-2-dependent responses in macrophages, many of which are MyD88
      independent. We have also demonstrated that the mmLDL activation leads to
      recruitment of spleen tyrosine kinase (Syk) to TLR4 and TLR4 and Syk
      phosphorylation. In this study, we produced a macrophage-specific Syk knockout
      mouse and used primary Syk(-/-) macrophages in our studies. We demonstrated that
      Syk mediated phosphorylation of ERK1/2 and JNK, which in turn phosphorylated c
      Fos and c-Jun, respectively, as assessed by an in vitro kinase assay. c-Jun
      phosphorylation was also mediated by IKKepsilon. c-Jun and c-Fos bound to
      consensus DNA sites and thereby completed an AP-1 transcriptional complex and
      induced expression of CXCL2 and IL-6. These results suggest that Syk plays a key
      role in TLR4-mediated macrophage responses to host-generated ligands, like mmLDL,
      with subsequent activation of an AP-1 transcription program.

PMID- 22384233
TI  - FTY720 suppresses liver tumor metastasis by reducing the population of
      circulating endothelial progenitor cells.
AB  - BACKGROUND: Surgical procedures such as liver resection and liver transplantation
      are the first-line treatments for hepatocellular carcinoma (HCC) patients.
      However, the high incidence of tumor recurrence and metastasis after liver
      surgery remains a major problem. Recent studies have shown that hepatic ischemia
      reperfusion (I/R) injury and endothelial progenitor cells (EPCs) contribute to
      tumor growth and metastasis. We aim to investigate the mechanism of FTY720, which
      was originally applied as an immunomodulator, on suppression of liver tumor
      metastasis after liver resection and partial hepatic I/R injury.
      METHODOLOGY/PRINCIPAL FINDINGS: An orthotopic liver tumor model in Buffalo rat
      was established using the hepatocellular carcinoma cell line McA-RH7777. Two
      weeks after orthotopic liver tumor implantation, the rats underwent liver
      resection for tumor-bearing lobe and partial hepatic I/R injury. FTY720 (2 mg/kg)
      was administered through the inferior caval vein before and after I/R injury.
      Blood samples were taken at days 0, 1, 3, 7, 14, 21 and 28 for detection of
      circulating EPCs (CD133+CD34+). Our results showed that intrahepatic and lung
      metastases were significantly inhibited together with less tumor angiogenesis by
      FTY720 treatment. The number of circulating EPCs was also significantly decreased
      by FTY720 treatment from day 7 to day 28. Hepatic gene expressions of CXCL10,
      VEGF, CXCR3, CXCR4 induced by hepatic I/R injury were down-regulated in the
      treatment group. CONCLUSIONS/SIGNIFICANCE: FTY720 suppressed liver tumor
      metastasis after liver resection marred by hepatic I/R injury in a rat liver
      tumor model by attenuating hepatic I/R injury and reducing circulating EPCs.

PMID- 22384234
TI  - Spores of Clostridium difficile clinical isolates display a diverse germination
      response to bile salts.
AB  - Clostridium difficile spores play a pivotal role in the transmission of
      infectious diarrhoea, but in order to cause disease spores must complete
      germination and return to vegetative cell growth. While the mechanisms of spore
      germination are well understood in Bacillus, knowledge of C. difficile
      germination remains limited. Previous studies have shown that bile salts and
      amino acids play an important role in regulating the germination response of C.
      difficile spores. Taurocholate, in combination with glycine, can stimulate
      germination, whereas chenodeoxycholate has been shown to inhibit spore
      germination in a C. difficile clinical isolate. Our recent studies of C.
      difficile sporulation characteristics have since pointed to substantial diversity
      among different clinical isolates. Consequently, in this study we investigated
      how the germination characteristics of different C. difficile isolates vary in
      response to bile salts. By analysing 29 isolates, including 16 belonging to the
      BI/NAP1/027 type, we show that considerable diversity exists in both the rate and
      extent of C. difficile germination in response to rich medium containing both
      taurocholate and glycine. Strikingly, we also show that although a potent
      inhibitor of germination for some isolates, chenodeoxycholate does not inhibit
      the germination, or outgrowth, of all C. difficile strains. Finally, we provide
      evidence that components of rich media may induce the germination of C. difficile
      spores, even in the absence of taurocholate. Taken together, these data suggest
      that the mechanisms of C. difficile spore germination in response to bile salts
      are complex and require further study. Furthermore, we stress the importance of
      studying multiple isolates in the future when analysing the nutrients or
      chemicals that either stimulate or inhibit C. difficile spore germination.

PMID- 22384235
TI  - Allelic origin of protease-sensitive and protease-resistant prion protein
      isoforms in Gerstmann-Straussler-Scheinker disease with the P102L mutation.
AB  - Gerstmann-Straussler-Scheinker (GSS) disease is a dominantly inherited prion
      disease associated with point mutations in the Prion Protein gene. The most
      frequent mutation associated with GSS involves a proline-to-leucine substitution
      at residue 102 of the prion protein, and is characterized by marked variability
      at clinical, pathological and molecular levels. Previous investigations of GSS
      P102L have shown that disease-associated pathological prion protein, or PrP(Sc),
      consists of two main conformers, which under exogenous proteolysis generates a
      core fragment of 21 kDa and an internal fragment of 8 kDa. Both conformers are
      detected in subjects with spongiform degeneration, whereas only the 8 kDa
      fragment is recovered in cases lacking spongiosis. Several studies have reported
      an exclusive derivation of protease-resistant PrP(Sc) isoforms from the mutated
      allele; however, more recently, the propagation of protease-resistant wild-type
      PrP(Sc) has been described. Here we analyze the molecular and pathological
      phenotype of six GSS P102L cases characterized by the presence of 21 and 8 kDa
      PrP fragments and two subjects with only the 8 kDa PrP fragment. Using sensitive
      protein separation techniques and Western blots with antibodies differentially
      recognizing wild-type and mutant PrP we observed a range of PrP(Sc) allelic
      conformers, either resistant or sensitive to protease treatment in all
      investigated subjects. Additionally, tissue deposition of protease-sensitive wild
      type PrP(Sc) molecules was seen by conventional PrP immunohistochemistry and
      paraffin-embedded tissue blot. Our findings enlarge the spectrum of
      conformational allelic PrP(Sc) quasispecies propagating in GSS P102L thus
      providing a molecular support to the spectrum of disease phenotypes, and, in
      addition, impact the diagnostic role of PrP immunohistochemistry in prion
      diseases.

PMID- 22384236
TI  - Diagnosis of Parkinson's disease based on disease-specific autoantibody profiles
      in human sera.
AB  - Parkinson's disease (PD), hallmarked by a variety of motor disorders and
      neurological decline, is the second most common neurodegenerative disease
      worldwide. Currently, no diagnostic test exists to identify sufferers, and
      physicians must rely on a combination of subjective physical and neurological
      assessments to make a diagnosis. The discovery of definitive blood-borne
      biomarkers would be a major step towards early and reliable diagnosis. Despite
      attention devoted to this search, such biomarkers have remained elusive. In the
      present study, we used human protein microarrays to reveal serum autoantibodies
      that are differentially expressed among PD and control subjects. The diagnostic
      significance of each of these autoantibodies was evaluated, resulting in the
      selection of 10 autoantibody biomarkers that can effectively differentiate PD
      sera from control sera with a sensitivity of 93.1% and specificity of 100%. PD
      sera were also distinguishable from sera obtained from Alzheimer's disease,
      breast cancer, and multiple sclerosis patients with accuracies of 86.0%, 96.6%,
      and 100%, respectively. Results demonstrate that serum autoantibodies can be used
      as highly specific and accurate biomarkers for PD diagnosis throughout the course
      of the disease.

PMID- 22384237
TI  - IP3 3-kinase opposes NGF driven neurite outgrowth.
AB  - The inositol (1,4,5) trisphosphate 3-kinases comprise a family of enzymes (A, B,
      and C) that phosphorylate the calcium mobilising molecule inositol (1,4,5)
      trisphosphate (IP(3)) to generate inositol (1,3,4,5) tetrakisphosphate. This
      molecule can function as a second messenger, but its roles are not completely
      understood. The A isoform of inositol (1,4,5) trisphosphate 3-kinase localises to
      filamentous actin within dendritic spines in the hippocampus and is implicated in
      the regulation of spine morphology and long term potentiation, however the
      mechanisms through which it signals in neuronal cells are not completely
      understood. We have used NGF driven neurite outgrowth from PC12 cells as a
      platform to examine the impact of signaling via inositol (1,4,5) trisphosphate 3
      kinase activity in a neuronal cell. We have found that the catalytic activity of
      the enzyme opposes neurite outgrowth, whilst pharmacological inhibition of
      inositol (1,4,5) trisphosphate 3-kinase leads to a significant increase in
      neurite outgrowth, and we show that the reduction in neurite outgrowth in
      response to inositol (1,4,5) trisphosphate 3-kinase activity correlates with
      reduced ERK activity as determined by western blotting using phosphorylation
      specific antibodies. Our findings suggest a novel neuronal signaling pathway
      linking metabolism of IP(3) to signaling via ERK.

PMID- 22384238
TI  - Contribution of various carbon sources toward isoprene biosynthesis in poplar
      leaves mediated by altered atmospheric CO2 concentrations.
AB  - Biogenically released isoprene plays important roles in both tropospheric
      photochemistry and plant metabolism. We performed a (13)CO(2)-labeling study
      using proton-transfer-reaction mass spectrometry (PTR-MS) to examine the kinetics
      of recently assimilated photosynthate into isoprene emitted from poplar (Populus
      * canescens) trees grown and measured at different atmospheric CO(2)
      concentrations. This is the first study to explicitly consider the effects of
      altered atmospheric CO(2) concentration on carbon partitioning to isoprene
      biosynthesis. We studied changes in the proportion of labeled carbon as a
      function of time in two mass fragments, M41(+), which represents, in part,
      substrate derived from pyruvate, and M69(+), which represents the whole unlabeled
      isoprene molecule. We observed a trend of slower (13)C incorporation into
      isoprene carbon derived from pyruvate, consistent with the previously
      hypothesized origin of chloroplastic pyruvate from cytosolic phosphenolpyruvate
      (PEP). Trees grown under sub-ambient CO(2) (190 ppmv) had rates of isoprene
      emission and rates of labeling of M41(+) and M69(+) that were nearly twice those
      observed in trees grown under elevated CO(2) (590 ppmv). However, they also
      demonstrated the lowest proportion of completely labeled isoprene molecules.
      These results suggest that under reduced atmospheric CO(2) availability, more
      carbon from stored/older carbon sources is involved in isoprene biosynthesis, and
      this carbon most likely enters the isoprene biosynthesis pathway through the
      pyruvate substrate. We offer direct evidence that extra-chloroplastic rather than
      chloroplastic carbon sources are mobilized to increase the availability of
      pyruvate required to up-regulate the isoprene biosynthesis pathway when trees are
      grown under sub-ambient CO(2).

PMID- 22384239
TI  - pcaGoPromoter--an R package for biological and regulatory interpretation of
      principal components in genome-wide gene expression data.
AB  - Analyzing data obtained from genome-wide gene expression experiments is
      challenging due to the quantity of variables, the need for multivariate analyses,
      and the demands of managing large amounts of data. Here we present the R package
      pcaGoPromoter, which facilitates the interpretation of genome-wide expression
      data and overcomes the aforementioned problems. In the first step, principal
      component analysis (PCA) is applied to survey any differences between experiments
      and possible groupings. The next step is the interpretation of the principal
      components with respect to both biological function and regulation by predicted
      transcription factor binding sites. The robustness of the results is evaluated
      using cross-validation, and illustrative plots of PCA scores and gene ontology
      terms are available. pcaGoPromoter works with any platform that uses gene symbols
      or Entrez IDs as probe identifiers. In addition, support for several popular
      Affymetrix GeneChip platforms is provided. To illustrate the features of the
      pcaGoPromoter package a serum stimulation experiment was performed and the genome
      wide gene expression in the resulting samples was profiled using the Affymetrix
      Human Genome U133 Plus 2.0 chip. Array data were analyzed using pcaGoPromoter
      package tools, resulting in a clear separation of the experiments into three
      groups: controls, serum only and serum with inhibitor. Functional annotation of
      the axes in the PCA score plot showed the expected serum-promoted biological
      processes, e.g., cell cycle progression and the predicted involvement of expected
      transcription factors, including E2F. In addition, unexpected results, e.g.,
      cholesterol synthesis in serum-depleted cells and NF-kappaB activation in
      inhibitor treated cells, were noted. In summary, the pcaGoPromoter R package
      provides a collection of tools for analyzing gene expression data. These tools
      give an overview of the input data via PCA, functional interpretation by gene
      ontology terms (biological processes), and an indication of the involvement of
      possible transcription factors.

PMID- 22384240
TI  - Intentional weight loss and dose reductions of anti-diabetic medications--a
      retrospective cohort study.
AB  - BACKGROUND AND AIM: Intentional weight loss, primarily by improving insulin
      resistance, is known to decrease the need for anti-diabetic medications. In this
      study, we assess the magnitude of weight loss that resulted in dose reductions or
      discontinuation of anti-diabetic medications in overweight or obese patients with
      type 2 diabetes (DM) undergoing weight loss treatment. METHODS: Case records of
      50 overweight or obese patients with DM who successfully decreased dosage or
      discontinued diabetes medications after losing weight via attendance at two
      University-based, outpatient weight management centers were analyzed. Follow-up
      visits, weight reduction interventions, and decisions for dose reductions or
      discontinuation of medications were individualized to patient needs by the
      treating physician. RESULTS: Mean starting BMI was 35 kg/m(2), mean age 53.4
      years, and 58% were male. All 50 used at least one anti-diabetic medication (30
      metformin, 39 sulfonylureas, 31 insulin, 21 sitagliptin) to manage blood sugar.
      Mean duration of follow-up was 30.2 months. Mean weight loss was 10.8 +/- 4.1 kgs
      (11.1% of initial body weight +/- 4.7%). 22/50 patients (44%) discontinued anti
      diabetes medications (14 sulfonylureas [36%], 7 insulin [23%], 4 sitagliptin
      [19%]). The mean percentage weight loss achieved at the point of successful
      discontinuation of medication was 11.2% +/- 3.5% (14% for sulphonylureas, 11% for
      insulin, and 7.1% for sitagliptin). Mean percentage weight loss of 5.6% +/- 2.8%
      (5.1% for sulphonylureas, 4.3% for insulin, and 7.1% for sitagliptin) was
      required for initial dose reduction. For every 5% weight loss, predicted dose
      reductions were sulphonylureas, 39%; insulin, 42%; and any anti-diabetic
      medications, 49%. CONCLUSION: Among overweight or obese patients with type 2
      diabetes, intentional weight loss of 7-14% was typically required for full
      discontinuation of at least one anti-diabetic medication. Discontinuation of
      insulin was achieved at a mean weight reduction of 11% of initial body weight.

PMID- 22384241
TI  - Ligand mobility modulates immunological synapse formation and T cell activation.
AB  - T cell receptor (TCR) engagement induces clustering and recruitment to the plasma
      membrane of many signaling molecules, including the protein tyrosine kinase zeta
      chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing
      leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in
      formation of the immunological synapse (IS), a dynamic protein array that
      modulates T cell activation. The current study investigates the effects of
      apparent long-range ligand mobility on T cell signaling activity and IS
      formation. We formed stimulatory lipid bilayers on glass surfaces from binary
      lipid mixtures with varied composition, and characterized these surfaces with
      respect to diffusion coefficient and fluid connectivity. Stimulatory ligands
      coupled to these surfaces with similar density and orientation showed differences
      in their ability to activate T cells. On less mobile membranes, central
      supramolecular activation cluster (cSMAC) formation was delayed and the overall
      accumulation of CD3zeta at the IS was reduced. Analysis of signaling microcluster
      (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer
      trajectories as a function of increased ligand mobility, whereas movement of
      SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was
      observed on all surfaces, but cell spreading and subsequent cytoskeletal
      contraction were more pronounced on mobile membranes. Finally, increased tyrosine
      phosphorylation and persistent elevation of intracellular Ca(2+) were observed in
      cells stimulated on fluid membranes. These results point to ligand mobility as an
      important parameter in modulating T cell responses.

PMID- 22384242
TI  - Mouse background strain profoundly influences Paneth cell function and intestinal
      microbial composition.
AB  - BACKGROUND: Increasing evidence supports the central role of Paneth cells in
      maintaining intestinal host-microbial homeostasis. However, the direct impact of
      host genotype on Paneth cell function remains unclear. Here, we characterize key
      differences in Paneth cell function and intestinal microbial composition in two
      widely utilized, genetically distinct mouse strains (C57BL/6 and 129/SvEv). In
      doing so, we demonstrate critical influences of host genotype on Paneth cell
      activity and the enteric microbiota. METHODOLOGY AND PRINCIPAL FINDINGS: Paneth
      cell numbers were determined by flow cytometry. Antimicrobial peptide (AMP)
      expression was evaluated using quantitative reverse-transcriptase polymerase
      chain reaction (qRT-PCR), acid urea-polyacrylamide gel electrophoresis, and mass
      spectrometry. Effects of mouse background on microbial composition were assessed
      by reciprocal colonization of germ-free mice from both background strains,
      followed by compositional analysis of resultant gut bacterial communities using
      terminal restriction fragment length polymorphism analysis and 16 S qPCR. Our
      results revealed that 129/SvEv mice possessed fewer Paneth cells and a divergent
      AMP profile relative to C57BL/6 counterparts. Novel 129/SvEv a-defensin peptides
      were identified, including Defa2/18v, Defa11, Defa16, and Defa18. Host genotype
      profoundly affected the global profile of the intestinal microbiota, while both
      source and host factors were found to influence specific bacterial groups.
      Interestingly, ileal alpha-defensins from 129/SvEv mice displayed attenuated
      antimicrobial activity against pro-inflammatory E. coli strains, a bacterial
      species found to be expanded in these animals. CONCLUSIONS AND SIGNIFICANCE: This
      work establishes the important impact of host genotype on Paneth cell function
      and the composition of the intestinal microbiota. It further identifies specific
      AMP and microbial alterations in two commonly used inbred mouse strains that have
      varying susceptibilities to a variety of disorders, ranging from obesity to
      intestinal inflammation. This will be critical for future studies utilizing these
      murine backgrounds to study the effects of Paneth cells and the intestinal
      microbiota on host health and disease.

PMID- 22384243
TI  - ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT,
      PDE4B, and DRD2.
AB  - ZNF804a was identified by a genome-wide association study (GWAS) in which a
      single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide
      statistical significance for association with a combined diagnosis of
      schizophrenia (SZ) and bipolar disorder. Although the molecular function of
      ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type
      zinc-finger domain and suggests ZNF804a plays a role in DNA binding and
      transcription. Here, we confirm that ZNF804a directly contributes to
      transcriptional control by regulating the expression of several SZ associated
      genes and directly interacts with chromatin proximal to the promoter regions of
      PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using
      immunochemistry we establish that ZNF804a is localized to the nucleus of rat
      neural progenitor cells in culture and in vivo. We demonstrate that expression of
      ZNF804a results in a significant increase in transcript levels of PRSS16 and
      COMT, relative to GFP transfected controls, and a statistically significant
      decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using
      chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and
      endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and
      COMT, suggesting a direct upregulation of transcription by ZNF804a on the
      expression of these genes. These results are the first to confirm that ZNF804a
      regulates transcription levels of four SZ associated genes, and binds to
      chromatin proximal to promoters of two SZ genes. These results suggest a model
      where ZNF804a may modulate a transcriptional network of SZ associated genes.

PMID- 22384244
TI  - Patterns and perceptions of climate change in a biodiversity conservation
      hotspot.
AB  - Quantifying local people's perceptions to climate change, and their assessments
      of which changes matter, is fundamental to addressing the dual challenge of land
      conservation and poverty alleviation in densely populated tropical regions To
      develop appropriate policies and responses, it will be important not only to
      anticipate the nature of expected changes, but also how they are perceived,
      interpreted and adapted to by local residents. The Albertine Rift region in East
      Africa is one of the world's most threatened biodiversity hotspots due to dense
      smallholder agriculture, high levels of land and resource pressures, and habitat
      loss and conversion. Results of three separate household surveys conducted in the
      vicinity of Kibale National Park during the late 2000s indicate that farmers are
      concerned with variable precipitation. Many survey respondents reported that
      conditions are drier and rainfall timing is becoming less predictable. Analysis
      of daily rainfall data for the climate normal period 1981 to 2010 indicates that
      total rainfall both within and across seasons has not changed significantly,
      although the timing and transitions of seasons has been highly variable. Results
      of rainfall data analysis also indicate significant changes in the intra-seasonal
      rainfall distribution, including longer dry periods within rainy seasons, which
      may contribute to the perceived decrease in rainfall and can compromise food
      security. Our results highlight the need for fine-scale climate information to
      assist agro-ecological communities in developing effective adaptive management.

PMID- 22384245
TI  - A prognostic gene expression profile that predicts circulating tumor cell
      presence in breast cancer patients.
AB  - The detection of circulating tumor cells (CTCs) in the peripheral blood and
      microarray gene expression profiling of the primary tumor are two promising new
      technologies able to provide valuable prognostic data for patients with breast
      cancer. Meta-analyses of several established prognostic breast cancer gene
      expression profiles in large patient cohorts have demonstrated that despite
      sharing few genes, their delineation of patients into "good prognosis" or "poor
      prognosis" are frequently very highly correlated, and combining prognostic
      profiles does not increase prognostic power. In the current study, we aimed to
      develop a novel profile which provided independent prognostic data by building a
      signature predictive of CTC status rather than outcome. Microarray gene
      expression data from an initial training cohort of 72 breast cancer patients for
      which CTC status had been determined in a previous study using a multimarker QPCR
      based assay was used to develop a CTC-predictive profile. The generated profile
      was validated in two independent datasets of 49 and 123 patients and confirmed to
      be both predictive of CTC status, and independently prognostic. Importantly, the
      "CTC profile" also provided prognostic information independent of the well
      established and powerful '70-gene' prognostic breast cancer signature. This
      profile therefore has the potential to not only add prognostic information to
      currently-available microarray tests but in some circumstances even replace blood
      based prognostic CTC tests at time of diagnosis for those patients already
      undergoing testing by multigene assays.

PMID- 22384247
TI  - Lower conditioning leisure-time physical activity in young adults born preterm at
      very low birth weight.
AB  - BACKGROUND: Adults born preterm at very low birth weight (VLBW, <1500 g) have
      elevated levels of risk factors for cardiovascular diseases and type 2 diabetes.
      Preliminary observations suggest that this could partly be explained by lower
      rates of physical activity. The aim of this study was to assess physical activity
      in healthy young adults born preterm at very low birth weight compared with term
      born controls. METHODOLOGY/PRINCIPAL FINDINGS: We studied 94 unimpaired young
      adults, aged 21-29 years, born at VLBW and 101 age-, sex-, and birth hospital
      matched term-born controls from one regional center in Southern Finland. The
      participants completed a validated 30-item 12-month physical activity
      questionnaire and the NEO-Personality Inventory based on the Big Five taxonomy,
      the most commonly used classification of personality traits. Yearly frequency,
      total time, total volume and energy expenditure of conditioning and non
      conditioning leisure-time physical activity (LTPA) and commuting physical
      activity were compared between VLBW and term-born subjects. A subset of
      participants underwent dual-energy x-ray absorptiometry for body composition
      measurement. Data were analyzed by multiple linear regression. Compared with
      controls, VLBW participants had lower frequency [-38.5% (95% CI; -58.9, -7.7)],
      total time [-47.4% (95% CI; -71.2, -4.1)], total volume [-44.3% (95% CI; -65.8, 
      9.2)] and energy expenditure [-55.9% (95% CI; -78.6, -9.4)] of conditioning LTPA
      when adjusted for age, sex, body mass index, smoking, parental education and
      personality traits. Adjusting for lean body mass instead of body mass index
      attenuated the difference. There were no differences in non-conditioning LTPA or
      commuting physical activity. CONCLUSIONS/SIGNIFICANCE: Compared with term-born
      controls, unimpaired VLBW adults undertake less frequent LTPA with lower total
      time and volume of exercise resulting in lower energy expenditure. Differences in
      personality that exist between the VLBW and term-born groups do not seem to
      explain this association.

PMID- 22384248
TI  - Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma
      pneumoniae in allergic lungs.
AB  - Surfactant protein-A (SP-A) has well-established functions in reducing bacterial
      and viral infections but its role in chronic lung diseases such as asthma is
      unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic
      asthmatics and is thought to contribute to exacerbations of asthma. Our lab has
      previously reported that during Mp infection of non-allergic airways, SP-A aides
      in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated
      response and, in allergic mice, SP-A regulates eosinophilic infiltration and
      inflammation of the airway. In the current study, we used an in vivo model with
      wild type (WT) and SP-A(-/-) allergic mice challenged with the model antigen
      ovalbumin (Ova) that were concurrently infected with Mp (Ova+Mp) to test the
      hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP
      A could protect allergic airways from injury due to release of eosinophil
      inflammatory products. SP-A deficient mice exhibit significant increases in
      inflammatory cells, mucus production and lung damage during concurrent allergic
      airway disease and infection (Ova+Mp) as compared to the WT mice of the same
      treatment group. In contrast, SP-A deficient mice have significantly decreased Mp
      burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase
      (EPO), which has been implicated in pathogen killing and also in epithelial
      dysfunction due to oxidative damage of resident lung proteins, is enhanced in
      samples from allergic/infected SP-A(-/-) mice as compared to WT mice. In vitro
      experiments using purified eosinophils and human SP-A suggest that SP-A limits
      the release of EPO from Mp-stimulated eosinophils thereby reducing their killing
      capacity. These findings are the first to demonstrate that although SP-A
      interferes with eosinophil-mediated biologic clearance of Mp by mediating the
      interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by
      limiting inflammation and damage.

PMID- 22384246
TI  - Conditionally immortalized mouse embryonic fibroblasts retain proliferative
      activity without compromising multipotent differentiation potential.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells which reside in many tissues
      and can give rise to multiple lineages including bone, cartilage and adipose.
      Although MSCs have attracted significant attention for basic and translational
      research, primary MSCs have limited life span in culture which hampers MSCs'
      broader applications. Here, we investigate if mouse mesenchymal progenitors can
      be conditionally immortalized with SV40 large T antigen and maintain long-term
      cell proliferation without compromising their multipotency. Using the system
      which expresses SV40 large T antigen flanked with Cre/loxP sites, we demonstrate
      that mouse embryonic fibroblasts (MEFs) can be efficiently immortalized by SV40
      large T antigen. The conditionally immortalized MEFs (iMEFs) exhibit an enhanced
      proliferative activity and maintain long-term cell proliferation, which can be
      reversed by Cre recombinase. The iMEFs express most MSC markers and retain
      multipotency as they can differentiate into osteogenic, chondrogenic and
      adipogenic lineages under appropriate differentiation conditions in vitro and in
      vivo. The removal of SV40 large T reduces the differentiation potential of iMEFs
      possibly due to the decreased progenitor expansion. Furthermore, the iMEFs are
      apparently not tumorigenic when they are subcutaneously injected into athymic
      nude mice. Thus, the conditionally immortalized iMEFs not only maintain long-term
      cell proliferation but also retain the ability to differentiate into multiple
      lineages. Our results suggest that the reversible immortalization strategy using
      SV40 large T antigen may be an efficient and safe approach to establishing long
      term cell culture of primary mesenchymal progenitors for basic and translational
      research, as well as for potential clinical applications.

PMID- 22384249
TI  - Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated
      by nutritional factors in obese human subjects.
AB  - BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue.
      These inflammatory cells affect adipocytes not only by classical cytokines but
      also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release
      the wnt5a inhibitor sFRP5. This protective effect, however, was found to be
      diminished in obesity. The aim of the present study was to examine (1) whether
      obese human subjects exhibit increased serum concentrations of wnt5a and (2)
      whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be
      influenced by caloric restriction. METHODOLOGY: 23 obese human subjects (BMI 44.1
      +/- 1.1 kg/m(2)) and 12 age- and sex-matched lean controls (BMI 22.3 +/- 0.4
      kg/m(2)) were included in the study. Obese subjects were treated with a very low
      calorie diet (approximately 800 kcal/d) for 12 weeks. Body composition was
      assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and
      the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were
      measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further
      determined on protein level by immunohistology. PRINCIPAL FINDINGS: Pro
      inflammatory wnt5a was not measurable in any serum sample of lean control
      subjects. In patients with obesity, however, wnt5a became significantly
      detectable consistent with low grade inflammation in such subjects. Caloric
      restriction resulted in a weight loss from 131.9 +/- 4.0 to 112.3 +/- 3.2 kg in
      the obese patients group. This was accompanied by a significant decrease of HOMA
      IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity.
      Interestingly, these metabolic improvements were associated with a significant
      increase in serum concentrations of the anti-inflammatory factor and wnt5a
      inhibitor sFRP5. CONCLUSIONS/SIGNIFICANCE: Obesity is associated with elevated
      serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric
      restriction beneficially affects serum concentrations of anti-inflammatory sFRP5
      in such subjects. These findings suggest a novel regulatory system in low grade
      inflammation in obesity, which can be influenced by nutritional therapy.

PMID- 22384250
TI  - Protein phosphatase magnesium dependent 1A (PPM1A) plays a role in the
      differentiation and survival processes of nerve cells.
AB  - The serine/threonine phosphatase type 2C (PPM1A) has a broad range of substrates,
      and its role in regulating stress response is well established. We have
      investigated the involvement of PPM1A in the survival and differentiation
      processes of PC6-3 cells, a subclone of the PC12 cell line. This cell line can
      differentiate into neuron like cells upon exposure to nerve growth factor (NGF).
      Overexpression of PPM1A in naive PC6-3 cells caused cell cycle arrest at the G2/M
      phase followed by apoptosis. Interestingly, PPM1A overexpression did not affect
      fully differentiated cells. Using PPM1A overexpressing cells and PPM1A knockdown
      cells, we show that this phosphatase affects NGF signaling in PC6-3 cells and is
      engaged in neurite outgrowth. In addition, the ablation of PPM1A interferes with
      NGF-induced growth arrest during differentiation of PC6-3 cells.

PMID- 22384251
TI  - Using support vector machines with multiple indices of diffusion for automated
      classification of mild cognitive impairment.
AB  - Few studies have looked at the potential of using diffusion tensor imaging (DTI)
      in conjunction with machine learning algorithms in order to automate the
      classification of healthy older subjects and subjects with mild cognitive
      impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI
      subjects in order to derive values for multiple indices of diffusion within the
      white matter voxels of each subject. DTI measures were then used together with
      support vector machines (SVMs) to classify control and MCI subjects. Greater than
      90% sensitivity and specificity was achieved using this method, demonstrating the
      potential of a joint DTI and SVM pipeline for fast, objective classification of
      healthy older and MCI subjects. Such tools may be useful for large scale drug
      trials in Alzheimer's disease where the early identification of subjects with MCI
      is critical.

PMID- 22384252
TI  - [11C]flumazenil binding is increased in a dose-dependent manner with tiagabine
      induced elevations in GABA levels.
AB  - Evidence indicates that synchronization of cortical activity at gamma-band
      frequencies, mediated through GABA-A receptors, is important for
      perceptual/cognitive processes. To study GABA signaling in vivo, we recently used
      a novel positron emission tomography (PET) paradigm measuring the change in
      binding of the benzodiazepine (BDZ) site radiotracer [(11)C]flumazenil associated
      with increases in extracellular GABA induced via GABA membrane transporter (GAT1)
      blockade with tiagabine. GAT1 blockade resulted in significant increases in
      [(11)C]flumazenil binding potential (BPND) over baseline in the major functional
      domains of the cortex, consistent with preclinical studies showing that increased
      GABA levels enhance the affinity of GABA-A receptors for BDZ ligands. In the
      current study we sought to replicate our previous results and to further validate
      this approach by demonstrating that the magnitude of increase in
      [(11)C]flumazenil binding observed with PET is directly correlated with tiagabine
      dose. [(11)C]flumazenil distribution volume (VT) was measured in 18 healthy
      volunteers before and after GAT1 blockade with tiagabine. Two dose groups were
      studied (n = 9 per group; Group I: tiagabine 0.15 mg/kg; Group II: tiagabine 0.25
      mg/kg). GAT1 blockade resulted in increases in mean (+/- SD) [(11)C]flumazenil VT
      in Group II in association cortices (6.8 +/- 0.8 mL g-1 vs. 7.3 +/- 0.4 mL g-1;p
      = 0.03), sensory cortices (6.7 +/- 0.8 mL g-1 vs. 7.3 +/- 0.5 mL g-1;p = 0.02)
      and limbic regions (5.2 +/- 0.6 mL g-1 vs. 5.7 +/- 0.3 mL g-1;p = 0.03). No
      change was observed at the low dose (Group I). Increased orbital frontal cortex
      binding of [(11)C]flumazenil in Group II correlated with the ability to entrain
      cortical networks (r = 0.67, p = 0.05) measured via EEG during a cognitive
      control task. These data provide a replication of our previous study
      demonstrating the ability to measure in vivo, with PET, acute shifts in
      extracellular GABA.

PMID- 22384253
TI  - Glutamate induces the elongation of early dendritic protrusions via mGluRs in
      wild type mice, but not in fragile X mice.
AB  - Fragile X syndrome (FXS), the most common inherited from of autism and mental
      impairment, is caused by transcriptional silencing of the Fmr1 gene, resulting in
      the loss of the RNA-binding protein FMRP. Dendritic spines of cortical pyramidal
      neurons in affected individuals are abnormally immature and in Fmr1 knockout (KO)
      mice they are also abnormally unstable. This could result in defects in
      synaptogenesis, because spine dynamics are critical for synapse formation. We
      have previously shown that the earliest dendritic protrusions, which are highly
      dynamic and might serve an exploratory role to reach out for axons, elongate in
      response to glutamate. Here, we tested the hypothesis that this process is
      mediated by metabotropic glutamate receptors (mGluRs) and that it is defective in
      Fmr1 KO mice. Using time-lapse imaging with two-photon microscopy in acute brain
      slices from early postnatal mice, we find that early dendritic protrusions in
      layer 2/3 neurons become longer in response to application of glutamate or DHPG,
      a Group 1 mGluR agonist. Blockade of mGluR5 signaling, which reverses some adult
      phenotypes of KO mice, prevented the glutamate-mediated elongation of early
      protrusions. In contrast, dendritic protrusions from KO mice failed to respond to
      glutamate. Thus, absence of FMRP may impair the ability of cortical pyramidal
      neurons to respond to glutamate released from nearby pre-synaptic terminals,
      which may be a critical step to initiate synaptogenesis and stabilize spines.

PMID- 22384254
TI  - HIF-1 and c-Src mediate increased glucose uptake induced by endothelin-1 and
      connexin43 in astrocytes.
AB  - In previous work we showed that endothelin-1 (ET-1) increases the rate of glucose
      uptake in astrocytes, an important aspect of brain function since glucose taken
      up by astrocytes is used to supply the neurons with metabolic substrates. In the
      present work we sought to identify the signalling pathway responsible for this
      process in primary culture of rat astrocytes. Our results show that ET-1 promoted
      an increase in the transcription factor hypoxia-inducible factor-1alpha (HIF
      1alpha) in astrocytes, as shown in other cell types. Furthermore, HIF-1alpha
      siRNA experiments revealed that HIF-1alpha participates in the effects of ET-1 on
      glucose uptake and on the expression of GLUT-1, GLUT-3, type I and type II
      hexokinase. We previously reported that these effects of ET-1 are mediated by
      connexin43 (Cx43), the major gap junction protein in astrocytes. Indeed, our
      results show that silencing Cx43 increased HIF-1alpha and reduced the effect of
      ET-1 on HIF-1alpha, indicating that the effect of ET-1 on HIF-1alpha is mediated
      by Cx43. The activity of oncogenes such as c-Src can up-regulate HIF-1alpha.
      Since Cx43 interacts with c-Src, we investigated the participation of c-Src in
      this pathway. Interestingly, both the treatment with ET-1 and with Cx43-siRNA
      increased c-Src activity. In addition, when c-Src activity was inhibited neither
      ET-1 nor silencing Cx43 were able to up-regulate HIF-1alpha. In conclusion, our
      results suggest that ET-1 by down-regulating Cx43 activates c-Src, which in turn
      increases HIF-1alpha leading to the up-regulation of the machinery required to
      take up glucose in astrocytes. Cx43 expression can be reduced in response not
      only to ET-1 but also to various physiological and pathological stimuli. This
      study contributes to the identification of the signalling pathway evoked after
      Cx43 down-regulation that results in increased glucose uptake in astrocytes.
      Interestingly, this is the first evidence linking Cx43 to HIF-1, which is a
      master regulator of glucose metabolism.

PMID- 22384255
TI  - Cooperation of p300 and PCAF in the control of microRNA 200c/141 transcription
      and epithelial characteristics.
AB  - Epithelial to mesenchymal transition (EMT) not only occurs during embryonic
      development and in response to injury, but is an important element in cancer
      progression. EMT and its reverse process, mesenchymal to epithelial transition
      (MET) is controlled by a network of transcriptional regulators and can be
      influenced by posttranscriptional and posttranslational modifications. EMT/MET
      involves many effectors that can activate and repress these transitions, often
      yielding a spectrum of cell phenotypes. Recent studies have shown that the miR
      200 family and the transcriptional suppressor ZEB1 are important contributors to
      EMT. Our previous data showed that forced expression of SPRR2a was a powerful
      inducer of EMT and supports the findings by others that SPRR gene members are
      highly upregulated during epithelial remodeling in a variety of organs. Here,
      using SPRR2a cells, we characterize the role of acetyltransferases on the
      microRNA-200c/141 promoter and their effect on the epithelial/mesenchymal status
      of the cells. We show that the deacetylase inhibitor TSA as well as P300 and PCAF
      can cause a shift towards epithelial characteristics in HUCCT-1-SPRR2a cells. We
      demonstrate that both P300 and PCAF act as cofactors for ZEB1, forming a
      P300/PCAF/ZEB1 complex on the miR200c/141 promoter. This binding results in
      lysine acetylation of ZEB1 and a release of ZEB1 suppression on miR-200c/141
      transcription. Furthermore, disruption of P300 and PCAF interactions dramatically
      down regulates miR-200c/141 promoter activity, indicating a PCAF/P300 cooperative
      function in regulating the transcriptional suppressor/activator role of ZEB1.
      These data demonstrate a novel mechanism of miRNA regulation in mediating cell
      phenotype.

PMID- 22384256
TI  - Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular
      mechanisms of action of a novel BCR-JAK2 tyrosine-kinase.
AB  - Chromosomal translocations in tumors frequently produce fusion genes coding for
      chimeric proteins with a key role in oncogenesis. Recent reports described a BCR
      JAK2 fusion gene in fatal chronic and acute myeloid leukemia, but the functional
      behavior of the chimeric protein remains uncharacterized. We used fluorescence in
      situ hybridization and reverse transcription polymerase chain reaction (RT-PCR)
      assays to describe a BCR-JAK2 fusion gene from a patient with acute lymphoblastic
      leukemia. The patient has been in complete remission for six years following
      treatment and autologous transplantation, and minimal residual disease was
      monitored by real-time RT-PCR. BCR-JAK2 codes for a protein containing the BCR
      oligomerization domain fused to the JAK2 tyrosine-kinase domain. In vitro
      analysis of transfected cells showed that BCR-JAK2 is located in the cytoplasm.
      Transduction of hematopoietic Ba/F3 cells with retroviral vectors carrying BCR
      JAK2 induced IL-3-independent cell growth, constitutive activation of the
      chimeric protein as well as STAT5 phosphorylation and translocation to the
      nuclei, where Bcl-xL gene expression was elicited. Primary mouse progenitor cells
      transduced with BCR-JAK2 also showed increased proliferation and survival.
      Treatment with the JAK2 inhibitor TG101209 abrogated BCR-JAK2 and STAT5
      phosphorylation, decreased Bcl-xL expression and triggered apoptosis of
      transformed Ba/F3 cells. Therefore, BCR-JAK2 is a novel tyrosine-kinase with
      transforming activity. It deregulates growth factor-dependent proliferation and
      cell survival, which can be abrogated by the TG101209 inhibitor. Moreover,
      transformed Ba/F3 cells developed tumors when injected subcutaneously into nude
      mice, thus proving the tumorigenic capacity of BCR-JAK2 in vivo. Together these
      findings suggest that adult and pediatric patients with BCR-ABL-negative leukemia
      and JAK2 overexpression may benefit from targeted therapies.

PMID- 22384257
TI  - EGFR kinase promotes acquisition of stem cell-like properties: a potential
      therapeutic target in head and neck squamous cell carcinoma stem cells.
AB  - Members of the EGFR/ErbB family of tyrosine kinases are found to be highly
      expressed and deregulated in many cancers, including head and neck squamous cell
      carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play
      key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance.
      Recently, these characteristics have been linked to a small subpopulation of
      cells classified as cancer stem cells (CSCs) which are believed to be responsible
      for tumor initiation and maintenance. In this study, we investigated the possible
      role of EGFR as a regulator of "stemness" in HNSCC cells. Activation of EGFR by
      the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC
      cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4,
      NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased
      tumorsphere formation, a characteristic ability of cancer stem cells. Conversely,
      treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in
      decreased expression of the aforementioned genes, and loss of tumorsphere-forming
      ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture
      derived from a fresh HNSCC tumor, confirming our findings for the cell lines.
      Additionally, we found that these putative cancer stem cells, when treated with
      Gefitinib, possessed a lower capacity to invade and became more sensitive to
      cisplatin-induced death in vitro. These results suggest that EGFR plays critical
      roles in the survival, maintenance, and function of cancer stem cells. Drugs that
      target EGFR, perhaps administered in combination with conventional chemotherapy,
      might be an effective treatment for HNSCC.

PMID- 22384258
TI  - Acceptability of early infant male circumcision as an HIV prevention intervention
      in Zimbabwe: a qualitative perspective.
AB  - BACKGROUND: Early infant male circumcision (EIMC) is simpler, safer and more cost
      effective than adult circumcision. In sub-Saharan Africa, there are concerns
      about acceptability of EIMC which could affect uptake. In 2009 a quantitative
      survey of 2,746 rural Zimbabweans (aged 18-44) indicated that 60% of women and
      58% of men would be willing to have their newborn son circumcised. Willingness
      was associated with knowledge of HIV and male circumcision. This qualitative
      study was conducted to better understand this issue. METHODS: In 2010, 24 group
      discussions were held across Zimbabwe with participants from seven ethnic groups.
      Additionally, key informant interviews were held with private paediatricians who
      offer EIMC (n = 2) plus one traditional leader. Discussions were audio-recorded,
      transcribed, translated into English (where necessary), coded using NVivo 8 and
      analysed using grounded theory principles. RESULTS: Knowledge of the procedure
      was poor. Despite this, acceptability of EIMC was high among parents from most
      ethnic groups. Discussions suggested that fathers would make the ultimate
      decision regarding EIMC although mothers and extended family can have (often
      covert) influence. Participants' concerns centred on: safety, motive behind free
      service provision plus handling and disposal of the discarded foreskin. Older men
      from the dominant traditionally circumcising population strongly opposed EIMC,
      arguing that it separates circumcision from adolescent initiation, as well as
      allowing women (mothers) to nurse the wound, considered taboo. CONCLUSIONS: EIMC
      is likely to be an acceptable HIV prevention intervention for most populations in
      Zimbabwe, if barriers to uptake are appropriately addressed and fathers are
      specifically targeted by the programme.

PMID- 22384260
TI  - Revisiting gender differences in somatic symptoms of depression: much ado about
      nothing?
AB  - BACKGROUND: Women have a higher prevalence of Major Depressive Disorder (MDD) and
      report more severe depressive symptoms than men. Several studies have suggested
      that gender differences in depression may occur because women report higher
      levels of somatic symptoms than men. Those studies, however, have not controlled
      or matched for non-somatic symptoms. The objective of this study was to examine
      if women report relatively more somatic symptoms than men matched on
      cognitive/affective symptoms. METHODS: Male and female patients receiving
      treatment for MDD in outpatient psychiatric clinics in New Jersey and
      Pennsylvania, USA were matched on Beck Depression Inventory-II (BDI-II)
      cognitive/affective symptom scores. Male and female BDI-II somatic symptom scores
      were compared using independent samples 2-tailed t-tests. RESULTS: Of 472 male
      and 1,026 female patients, there were 470 male patients (mean age = 40.1 years,
      SD = 15.1) and 470 female patients (mean age = 43.1 years, SD = 17.2)
      successfully matched on BDI-II cognitive/affective symptom scores. Somatic
      symptoms accounted for 35% of total BDI-II scores for male patients versus 38%
      for matched female patients. Female patients had somatic symptom scores on
      average 1.3 points higher than males (p<.001), equivalent to 4% of the total BDI
      II scores of female patients. Only 5% of male patients and 7% of female patients
      scored 2 or higher on all BDI-II somatic symptom items. CONCLUSIONS: Gender
      differences in somatic scores were very small. Thus, differences in the
      experience and reporting of somatic symptoms would not likely explain gender
      differences in depression rates and symptom severity.

PMID- 22384259
TI  - Mechanisms of loss of functions of human angiogenin variants implicated in
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: Mutations in the coding region of angiogenin (ANG) gene have been
      found in patients suffering from Amyotrophic Lateral Sclerosis (ALS).
      Neurodegeneration results from the loss of angiogenic ability of ANG (protein
      coded by ANG). In this work, we performed extensive molecular dynamics (MD)
      simulations of wild-type ANG and disease associated ANG variants to elucidate the
      mechanism behind the loss of ribonucleolytic activity and nuclear translocation
      activity, functions needed for angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: MD
      simulations were carried out to study the structural and dynamic differences in
      the catalytic site and nuclear localization signal residues between WT-ANG (Wild
      type ANG) and six mutants. Variants K17I, S28N, P112L and V113I have confirmed
      association with ALS, while T195C and A238G single nucleotide polymorphisms
      (SNPs) encoding L35P and K60E mutants respectively, have not been associated with
      ALS. Our results show that loss of ribonucleolytic activity in K17I is caused by
      conformational switching of the catalytic residue His114 by 99 degrees . The loss
      of nuclear translocation activity of S28N and P112L is caused by changes in the
      folding of the residues (31)RRR(33) that result in the reduction in solvent
      accessible surface area (SASA). Consequently, we predict that V113I will exhibit
      loss of angiogenic properties by loss of nuclear translocation activity and L35P
      by loss of both ribonucleolytic activity and nuclear translocation activity. No
      functional loss was inferred for K60E. The MD simulation results were supported
      by hydrogen bond interaction analyses and molecular docking studies.
      CONCLUSIONS/SIGNIFICANCE: Conformational switching of catalytic residue His114
      seems to be the mechanism causing loss of ribonucleolytic activity and reduction
      in SASA of nuclear localization signal residues (31)RRR(33) results in loss of
      nuclear translocation activity in ANG mutants. Therefore, we predict that L35P
      mutant, would exhibit loss of angiogenic functions, and hence would correlate
      with ALS while K60E would not show any loss.

PMID- 22384261
TI  - Kruppel-like factor 4 regulates intestinal epithelial cell morphology and
      polarity.
AB  - Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a
      vital role in regulating cell lineage differentiation during development and
      maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is
      predominantly expressed in the differentiated epithelial cells. It has been
      identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice
      demonstrated a decrease in number of goblet cells in the colon, and conditional
      ablation of KLF4 from the intestinal epithelium led to altered epithelial
      homeostasis. However, the role of KLF4 in differentiated intestinal cells and
      colon cancer cells, as well as the mechanism by which it regulates homeostasis
      and represses tumorigenesis in the intestine is not well understood. In our
      study, KLF4 was partially depleted in the differentiated intestinal epithelial
      cells by a tamoxifen-inducible Cre recombinase. We found a significant increase
      in the number of goblet cells in the KLF4-deleted small intestine, suggesting
      that KLF4 is not only required for goblet cell differentiation, but also required
      for maintaining goblet cell numbers through its function in inhibiting cell
      proliferation. The number and position of Paneth cells also changed. This is
      consistent with the KLF4 knockout study using villin-Cre [1]. Through
      immunohistochemistry (IHC) staining and statistical analysis, we found that a
      stem cell and/or tuft cell marker, DCAMKL1, and a proliferation marker, Ki67, are
      affected by KLF4 depletion, while an enteroendocrine cell marker, neurotensin
      (NT), was not affected. In addition, we found KLF4 depletion altered the
      morphology and polarity of the intestinal epithelial cells. Using a three
      dimensional (3D) intestinal epithelial cyst formation assay, we found that KLF4
      is essential for cell polarity and crypt-cyst formation in human colon cancer
      cells. These findings suggest that, as a tumor suppressor in colorectal cancer,
      KLF4 affects intestinal epithelial cell morphology by regulating proliferation,
      differentiation and polarity of the cells.

PMID- 22384262
TI  - Sample preparation and liquid chromatography-tandem mass spectrometry for
      multiple steroids in mammalian and avian circulation.
AB  - Blood samples from wild mammals and birds are often limited in volume, allowing
      researchers to quantify only one or two steroids from a single sample by
      immunoassays. In addition, wildlife serum or plasma samples are often lipemic,
      necessitating stringent sample preparation. Here, we validated sample preparation
      for simultaneous liquid chromatography--tandem mass spectrometry (LC-MS/MS)
      quantitation of cortisol, corticosterone, 11-deoxycortisol,
      dehydroepiandrosterone (DHEA), 17beta-estradiol, progesterone, 17alpha
      hydroxyprogesterone and testosterone from diverse mammalian (7 species) and avian
      (5 species) samples. Using 100 uL of serum or plasma, we quantified (signal-to
      noise (S/N) ratio >= 10) 4-7 steroids depending on the species and sample,
      without derivatization. Steroids were extracted from serum or plasma using
      automated solid-phase extraction where samples were loaded onto C18 columns,
      washed with water and hexane, and then eluted with ethyl acetate. Quantitation by
      LC-MS/MS was done in positive ion, multiple reaction-monitoring (MRM) mode with
      an atmospheric pressure chemical ionization (APCI) source and heated nebulizer
      (500 degrees C). Deuterated steroids served as internal standards and run time
      was 15 minutes. Extraction recoveries were 87-101% for the 8 analytes, and all
      intra- and inter-run CVs were <= 8.25%. This quantitation method yields good
      recoveries with variable lipid-content samples, avoids antibody cross-reactivity
      issues, and delivers results for multiple steroids. Thus, this method can enrich
      datasets by providing simultaneous quantitation of multiple steroids, and allow
      researchers to reimagine the hypotheses that could be tested with their volume
      limited, lipemic, wildlife samples.

PMID- 22384263
TI  - Stability, entrapment and variant formation of Salmonella genomic island 1.
AB  - BACKGROUND: The Salmonella genomic island 1 (SGI1) is a 42.4 kb integrative
      mobilizable element containing several antibiotic resistance determinants
      embedded in a complex integron segment In104. The numerous SGI1 variants
      identified so far, differ mainly in this segment and the explanations of their
      emergence were mostly based on comparative structure analyses. Here we provide
      experimental studies on the stability, entrapment and variant formation of this
      peculiar gene cluster originally found in S. Typhimurium. METHODOLOGY/PRINCIPAL
      FINDINGS: Segregation and conjugation tests and various molecular techniques were
      used to detect the emerging SGI1 variants in Salmonella populations of 17
      Salmonella enterica serovar Typhimurium DT104 isolates from Hungary. The SGI1s in
      these isolates proved to be fully competent in excision, conjugal transfer by the
      IncA/C helper plasmid R55, and integration into the E. coli chromosome. A trap
      vector has been constructed and successfully applied to capture the island on a
      plasmid. Monitoring of segregation of SGI1 indicated high stability of the
      island. SGI1-free segregants did not accumulate during long-term propagation, but
      several SGI1 variants could be obtained. Most of them appeared to be identical to
      SGI1-B and SGI1-C, but two new variants caused by deletions via a short-homology
      dependent recombination process have also been detected. We have also noticed
      that the presence of the conjugation helper plasmid increased the formation of
      these deletion variants considerably. CONCLUSIONS/SIGNIFICANCE: Despite that
      excision of SGI1 from the chromosome was proven in SGI1(+)Salmonella populations,
      its complete loss could not be observed. On the other hand, we demonstrated that
      several variants, among them two newly identified ones, arose with detectable
      frequencies in these populations in a short timescale and their formation was
      promoted by the helper plasmid. This reflects that IncA/C helper plasmids are not
      only involved in the horizontal spreading of SGI1, but may also contribute to its
      evolution.

PMID- 22384264
TI  - Differential splicing alters subcellular localization of the alpha but not beta
      isoform of the MIER1 transcriptional regulator in breast cancer cells.
AB  - MIER1 was originally identified in a screen for novel fibroblast growth factor
      activated early response genes. The mier1 gene gives rise to multiple transcripts
      encoding protein isoforms that differ in their amino (N-) and carboxy (C-)
      termini. Much of the work to date has focused on the two C-terminal variants,
      MIER1alpha and beta, both of which have been shown to function as transcriptional
      repressors. Our previous work revealed a dramatic shift in MIER1alpha subcellular
      localization from nuclear in normal breast tissue to cytoplasmic in invasive
      breast carcinoma, suggesting that loss of nuclear MIER1alpha may play a role in
      breast cancer development. In the present study, we investigated whether
      alternative splicing to include a cassette exon and produce an N-terminal variant
      of MIER1alpha affects its subcellular localization in MCF7 breast carcinoma
      cells. We demonstrate that this cassette exon, exon 3A, encodes a consensus
      leucine-rich nuclear export signal (NES). Inclusion of this exon in MIER1alpha to
      produce the MIER1-3Aalpha isoform altered its subcellular distribution in MCF7
      cells from 81% nuclear to 2% nuclear and this change in localization was
      abrogated by mutation of critical leucines within the NES. Treatment with
      leptomycin B (LMB), an inhibitor of the nuclear export receptor CRM1, resulted in
      a significant increase in the percentage of cells with nuclear MIER1-3Aalpha,
      from 4% to 53%, demonstrating that cytoplasmic localization of this isoform was
      due to CRM1-dependent nuclear export. Inclusion of exon 3A in MIER1beta to
      produce the N-terminal variant MIER1-3Abeta however had little effect on the
      nuclear targeting of this isoform. Our results demonstrate that alternative
      splicing to include exon 3A specifically affects the localization pattern of the
      alpha isoform.

PMID- 22384265
TI  - Resting-state quantitative electroencephalography reveals increased
      neurophysiologic connectivity in depression.
AB  - Symptoms of Major Depressive Disorder (MDD) are hypothesized to arise from
      dysfunction in brain networks linking the limbic system and cortical regions.
      Alterations in brain functional cortical connectivity in resting-state networks
      have been detected with functional imaging techniques, but neurophysiologic
      connectivity measures have not been systematically examined. We used weighted
      network analysis to examine resting state functional connectivity as measured by
      quantitative electroencephalographic (qEEG) coherence in 121 unmedicated subjects
      with MDD and 37 healthy controls. Subjects with MDD had significantly higher
      overall coherence as compared to controls in the delta (0.5-4 Hz), theta (4-8
      Hz), alpha (8-12 Hz), and beta (12-20 Hz) frequency bands. The frontopolar region
      contained the greatest number of "hub nodes" (surface recording locations) with
      high connectivity. MDD subjects expressed higher theta and alpha coherence
      primarily in longer distance connections between frontopolar and temporal or
      parietooccipital regions, and higher beta coherence primarily in connections
      within and between electrodes overlying the dorsolateral prefrontal cortical
      (DLPFC) or temporal regions. Nearest centroid analysis indicated that MDD
      subjects were best characterized by six alpha band connections primarily
      involving the prefrontal region. The present findings indicate a loss of
      selectivity in resting functional connectivity in MDD. The overall greater
      coherence observed in depressed subjects establishes a new context for the
      interpretation of previous studies showing differences in frontal alpha power and
      synchrony between subjects with MDD and normal controls. These results can inform
      the development of qEEG state and trait biomarkers for MDD.

PMID- 22384266
TI  - Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted aspartic
      protease.
AB  - BACKGROUND: Candida albicans, a commensal organism, is a part of the normal flora
      of healthy individuals. However, once the host immunity is compromised, C.
      albicans opportunistically causes recurrent superficial or fatal systemic
      candidiasis. Secreted aspartic proteases (Sap), encoded by 10 types of SAP genes,
      have been suggested to contribute to various virulence processes. Thus, it is
      important to elucidate their biochemical properties for better understanding of
      the molecular mechanisms that how Sap isozymes damage host tissues.
      METHODOLOGY/PRINCIPAL FINDINGS: The SAP7 gene was cloned from C. albicans SC5314
      and heterogeneously produced by Pichia pastoris. Measurement of Sap7 proteolytic
      activity using the FRETS-25Ala library showed that Sap7 was a pepstatin A
      insensitive protease. To understand why Sap7 was insensitive to pepstatin A,
      alanine substitution mutants of Sap7 were constructed. We found that M242A and
      T467A mutants had normal proteolytic activity and sensitivity to pepstatin A.
      M242 and T467 were located in close proximity to the entrance to an active site,
      and alanine substitution at these positions widened the entrance. Our results
      suggest that this alteration might allow increased accessibility of pepstatin A
      to the active site. This inference was supported by the observation that the
      T467A mutant has stronger proteolytic activity than the wild type.
      CONCLUSIONS/SIGNIFICANCE: We found that Sap7 was a pepstatin A-insensitive
      protease, and that M242 and T467 restricted the accessibility of pepstatin A to
      the active site. This finding will lead to the development of a novel protease
      inhibitor beyond pepstatin A. Such a novel inhibitor will be an important
      research tool as well as pharmaceutical agent for patients suffering from
      candidiasis.

PMID- 22384267
TI  - Anti-idiotypic antibody specific to GAD65 autoantibody prevents type 1 diabetes
      in the NOD mouse.
AB  - Overt autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab)
      are a characteristic in patients with Type 1 diabetes (T1D). Anti-idiotypic
      antibodies (anti-Id) directed to GAD65Ab effectively prevent the binding of GAD65
      to GAD65Ab in healthy individuals. Levels of GAD65Ab-specific anti-Id are
      significantly lower in patients with T1D, leading to overt GAD65Ab in these
      patients. To determine the possible protective role of GAD65Ab-specific anti-Id
      in T1D pathogenesis, we developed the monoclonal anti-Id MAb 8E6G4 specifically
      targeting human monoclonal GAD65Ab b96.11. MAb 8E6G4 was demonstrated as a
      specific anti-Id directed to the antigen binding site of b96.11. MAb 8E6G4
      recognized human antibodies in sera from healthy individuals, T2D patients, and
      T1D patients as established by ELISA. We confirmed these MAb 8E6G4-bound human
      antibodies to contain GAD65Ab by testing the eluted antibodies for binding to
      GAD65 in radioligand binding assays. These findings confirm that GAD65Ab are
      present in sera of individuals, who test GAD65Ab-negative in conventional
      detection assays. To test our hypothesis that GAD65Ab-specific anti-Id have an
      immune modulatory role in T1D, we injected young Non Obese Diabetic (NOD) mice
      with MAb 8E6G4. The animals were carefully monitored for development of T1D for
      40 weeks. Infiltration of pancreatic islets by mononuclear cells (insulitis) was
      determined to establish the extent of an autoimmune attack on the pancreatic
      islets. Administration of MAb 8E6G4 significantly reduced the cumulative
      incidence rate of T1D and delayed the time of onset. Insulitis was significantly
      less severe in animals that received MAb 8E6G4 as compared to control animals.
      These results support our hypothesis that anti-Id specific to GAD65Ab have a
      protective role in T1D.

PMID- 22384268
TI  - Structure based design and synthesis of peptide inhibitor of human LOX-12: in
      vitro and in vivo analysis of a novel therapeutic agent for breast cancer.
AB  - Human breast cancer cell proliferation involves a complex interaction between
      growth factors, steroid hormones and peptide hormones. The interaction of growth
      factors, such as epidermal growth factor (EGF), with their receptors on breast
      cancer cells can lead to the hydrolysis of phospholipids and release of fatty
      acid such as arachidonic acid, which can be further metabolized by cyclooxygenase
      (COX) and lipoxygenase (LOX) pathways to produce prostaglandins. The high
      concentration of prostaglandins has been associated with chronic inflammatory
      diseases and several types of human cancers. This is due to the over expression
      COX, LOX and other inflammatory enzymes. Ten peptides were designed and
      synthesized by solid phase peptide synthesis and analyzed in vitro for enzyme
      inhibition. Out of these peptides, YWCS had shown significant inhibitory effects.
      The dissociation constant (K(D)) was determined by surface plasmon resonance
      (SPR) analysis and was found to be 3.39 * 10(-8) M and 8.6 * 10(-8) M for YWCS
      and baicalein (positive control), respectively. The kinetic constant Ki was 72.45
      * 10(-7) M as determined by kinetic assay. The peptide significantly reduced the
      cell viability of estrogen positive MCF-7 and estrogen negative MDA-MB-231 cell
      line with the half maximal concentration (IC(50)) of 75 uM and 400 uM,
      respectively. The peptide also induced 49.8% and 20.8% apoptosis in breast cancer
      cells MCF-7 and MDA-MB-231, respectively. The YWCS was also found to be least
      hemolytic at a concentration of 358 uM. In vivo studies had shown that the
      peptide significantly inhibits tumor growth in mice (p<0.017). This peptide can
      be used as a lead compound and complement for ongoing efforts to develop
      differentiation therapies for breast cancer.

PMID- 22384269
TI  - Sigma E regulators control hemolytic activity and virulence in a shrimp
      pathogenic Vibrio harveyi.
AB  - Members of the genus Vibrio are important marine and aquaculture pathogens.
      Hemolytic activity has been identified as a virulence factor in many pathogenic
      vibrios including V. cholerae, V. parahaemolyticus, V. alginolyticus, V. harveyi
      and V. vulnificus. We have used transposon mutagenesis to identify genes involved
      in the hemolytic activity of shrimp-pathogenic V. harveyi strain PSU3316. Out of
      1,764 mutants screened, five mutants showed reduced hemolytic activity on sheep
      blood agar and exhibited virulence attenuation in shrimp (Litopenaeus vannamei).
      Mutants were identified by comparing transposon junction sequences to a draft of
      assembly of the PSU3316 genome. Surprisingly none of the disrupted open reading
      frames or gene neighborhoods contained genes annotated as hemolysins. The gene
      encoding RseB, a negative regulator of the sigma factor (sigma(E)), was
      interrupted in 2 out of 5 transposon mutants, in addition, the transcription
      factor CytR, a threonine synthetase, and an efflux-associated cytoplasmic protein
      were also identified. Knockout mutations introduced into the rpoE operon at the
      rseB gene exhibited low hemolytic activity in sheep blood agar, and were 3-to 7
      fold attenuated for colonization in shrimp. Comparison of whole cell extracted
      proteins in the rseB mutant (PSU4030) to the wild-type by 2-D gel electrophoresis
      revealed 6 differentially expressed proteins, including two down-regulated porins
      (OmpC-like and OmpN) and an upregulated protease (DegQ) which have been
      associated with sigma(E) in other organisms. Our study is the first report
      linking hemolytic activity to the sigma(E) regulators in pathogenic Vibrio
      species and suggests expression of this virulence-linked phenotype is governed by
      multiple regulatory pathways within the V. harveyi.

PMID- 22384270
TI  - High post-capture survival for sharks, rays and chimaeras discarded in the main
      shark fishery of Australia?
AB  - Most sharks, rays and chimaeras (chondrichthyans) taken in commercial fisheries
      are discarded (i.e. returned to the ocean either dead or alive). Quantifying the
      post-capture survival (PCS) of discarded species is therefore essential for the
      improved management and conservation of this group. For all chondrichthyans taken
      in the main shark fishery of Australia, we quantified the immediate PCS of
      individuals reaching the deck of commercial shark gillnet fishing vessels and
      applied a risk-based method to semi-quantitatively determine delayed and total
      PCS. Estimates of immediate, delayed and total PCS were consistent, being very
      high for the most commonly discarded species (Port Jackson shark, Australian
      swellshark, and spikey dogfish) and low for the most important commercial species
      (gummy and school sharks). Increasing gillnet soak time or water temperature
      significantly decreased PCS. Chondrichthyans with bottom-dwelling habits had the
      highest PCS whereas those with pelagic habits had the lowest PCS. The risk-based
      approach can be easily implemented as a standard practice of on-board observing
      programs, providing a convenient first-step assessment of the PCS of all species
      taken in commercial fisheries.

PMID- 22384271
TI  - Analysis of precore/core covariances associated with viral kinetics and genotypes
      in hepatitis B e antigen-positive chronic hepatitis B patients.
AB  - Hepatitis B virus (HBV) is one of the most common DNA viruses that can cause
      aggressive hepatitis, cirrhosis and hepatocellular carcinoma. Although many
      people are persistently infected with HBV, the kinetics in serum levels of viral
      loads and the host immune responses vary from person to person. HBV precore/core
      open reading frame (ORF) encoding proteins, hepatitis B e antigen (HBeAg) and
      core antigen (HBcAg), are two indicators of active viral replication. The aim of
      this study was to discover a variety of amino acid covariances in responses to
      viral kinetics, seroconversion and genotypes during the course of HBV infection.
      A one year follow-up study was conducted with a total number of 1,694 clones from
      23 HBeAg-positive chronic hepatitis B patients. Serum alanine aminotransferase,
      HBV DNA and HBeAg levels were measured monthly as criteria for clustering
      patients into several different subgroups. Monthly derived multiple precore/core
      ORFs were directly sequenced and translated into amino acid sequences. For each
      subgroup, time-dependent covariances were identified from their time-varying
      sequences over the entire follow-up period. The fluctuating, wavering, HBeAg
      nonseroconversion and genotype C subgroups showed greater degrees of covariances
      than the stationary, declining, HBeAg-seroconversion and genotype B. Referring to
      literature, mutation hotspots within our identified covariances were associated
      with the infection process. Remarkably, hotspots were predominant in genotype C.
      Moreover, covariances were also identified at early stage (spanning from baseline
      to a peak of serum HBV DNA) in order to determine the intersections with
      aforementioned time-dependent covariances. Preserved covariances, namely
      representative covariances, of each subgroup are visually presented using a tree
      based structure. Our results suggested that identified covariances were strongly
      associated with viral kinetics, seroconversion and genotypes. Moreover,
      representative covariances may benefit clinicians to prescribe a suitable
      treatment for patients even if they have no obvious symptoms at the early stage
      of HBV infection.

PMID- 22384272
TI  - Expression of high-affinity IgE receptor on human peripheral blood dendritic
      cells in children.
AB  - BACKGROUND: In a mouse model of viral induced atopic disease, expression of
      FcepsilonRI on dendritic cells is critical. While adult human conventional (cDC)
      and plasmacytoid (pDC) dendritic cells have been shown to express FcepsilonRI, it
      is not known if this receptor is expressed in childhood and how its expression is
      governed by IgE. METHODS: Following informed consent of subjects (n = 27, aged 12
      188 months), peripheral blood was stained for surface expression of CD19, ILT7,
      CD1c, IgE, FcepsilonRI and analyzed by flow cytometry (cDC: CD19(-) ILT7(-)
      CD1c(+); pDC: CD19(-) ILT7(+) CD1c(-)). Total and specific serum IgE levels to
      food and inhalant allergens were determined by ImmunoCAP, and the relationship
      between FcepsilonRI expression on dendritic cells and sensitization, free IgE,
      cell bound IgE, and age was determined. RESULTS: Independent of sensitization
      status, FcepsilonRI expression was noted on cDC and pDC as early as 12 months of
      age. Serum IgE level correlated with expression of FcepsilonRI on cDC, but not
      pDC. Based on the concentration of IgE, a complex relationship was found between
      surface bound IgE and expression of FcepsilonRI on cDC. pDC exhibited a linear
      relationship of FcepsilonRI expression and bound IgE that was consistent through
      all IgE concentrations. CONCLUSIONS: In children, FcepsilonRI expression on cDC
      and pDC is modulated differently by serum and cell bound IgE. IgE governance of
      FcepsilonRI expression on cDC depends upon a complex relationship. Further
      studies are needed to determine the functional roles of FcepsilonRI on cDC and
      pDC.

PMID- 22384273
TI  - gamma-Aminobutyric acid transporter 2 mediates the hepatic uptake of
      guanidinoacetate, the creatine biosynthetic precursor, in rats.
AB  - Guanidinoacetic acid (GAA) is the biosynthetic precursor of creatine which is
      involved in storage and transmission of phosphate-bound energy. Hepatocytes
      readily convert GAA to creatine, raising the possibility that the active uptake
      of GAA by hepatocytes is a regulatory factor. The purpose of this study is to
      investigate and identify the transporter responsible for GAA uptake by
      hepatocytes. The characteristics of [(14)C]GAA uptake by hepatocytes were
      elucidated using the in vivo liver uptake method, freshly isolated rat
      hepatocytes, an expression system of Xenopus laevis oocytes, gene knockdown, and
      an immunohistochemical technique. In vivo injection of [(14)C]GAA into the rat
      femoral vein and portal vein results in the rapid uptake of [(14)C]GAA by the
      liver. The uptake was markedly inhibited by gamma-aminobutyric acid (GABA) and
      nipecotinic acid, an inhibitor of GABA transporters (GATs). The characteristics
      of Na(+)- and Cl(-)-dependent [(14)C]GAA uptake by freshly isolated rat
      hepatocytes were consistent with those of GAT2. The Km value of the GAA uptake
      (134 uM) was close to that of GAT2-mediated GAA transport (78.9 uM). GABA caused
      a marked inhibition with an IC(50) value of 8.81 uM. The [(14)C]GAA uptake
      exhibited a significant reduction corresponding to the reduction in GAT2 protein
      expression. GAT2 was localized on the sinusoidal membrane of the hepatocytes
      predominantly in the periportal region. This distribution pattern was consistent
      with that of the creatine biosynthetic enzyme, S
      adenosylmethionine:guanidinoacetate N-methyltransferase. GAT2 makes a major
      contribution to the sinusoidal GAA uptake by periportal hepatocytes, thus
      regulating creatine biosynthesis in the liver.

PMID- 22384274
TI  - Motion and flexibility in human cytochrome p450 aromatase.
AB  - The crystal structures of human placental aromatase in complex with the substrate
      androstenedione and exemestane have revealed an androgen-specific active site and
      the structural basis for higher order organization. However, X-ray structures do
      not provide accounts of movements due to short-range fluctuations, ligand binding
      and protein-protein association. In this work, we conduct normal mode analysis
      (NMA) revealing the intrinsic fluctuations of aromatase, deduce the internal
      modes in membrane-free and membrane-integrated monomers as well as the
      intermolecular modes in oligomers, and propose a quaternary organization for the
      endoplasmic reticulum (ER) membrane integration. Dynamics of the crystallographic
      oligomers from NMA is found to be in agreement with the isotropic thermal factors
      from the X-ray analysis. Calculations of the root mean square fluctuations of the
      C-alpha atoms from their equilibrium positions confirm that the rigid-core
      structure of aromatase is intrinsic regardless of the changes in steroid binding
      interactions, and that aromatase self-association does not deteriorate the
      rigidity of the catalytic cleft. Furthermore, NMA on membrane-integrated
      aromatase shows that the internal modes in all likelihood contribute to breathing
      of the active site access channel. The collective intermolecular hinge bending
      and twisting modes provide the flexibility in the quaternary association
      necessary for membrane integration of the aromatase oligomers. Taken together,
      fluctuations of the active site, the access channel, and the heme-proximal
      cavity, and a dynamic quaternary organization could all be essential components
      of the functional aromatase in its role as an ER membrane-embedded steroidogenic
      enzyme.

PMID- 22384275
TI  - Interaction between hydrogenase maturation factors HypA and HypB is required for
      [NiFe]-hydrogenase maturation.
AB  - The active site of [NiFe]-hydrogenase contains nickel and iron coordinated by
      cysteine residues, cyanide and carbon monoxide. Metal chaperone proteins HypA and
      HypB are required for the nickel insertion step of [NiFe]-hydrogenase maturation.
      How HypA and HypB work together to deliver nickel to the catalytic core remains
      elusive. Here we demonstrated that HypA and HypB from Archaeoglobus fulgidus form
      1:1 heterodimer in solution and HypA does not interact with HypB dimer preloaded
      with GMPPNP and Ni. Based on the crystal structure of A. fulgidus HypB, mutants
      were designed to map the HypA binding site on HypB. Our results showed that two
      conserved residues, Tyr-4 and Leu-6, of A. fulgidus HypB are required for the
      interaction with HypA. Consistent with this observation, we demonstrated that the
      corresponding residues, Leu-78 and Val-80, located at the N-terminus of the
      GTPase domain of Escherichia coli HypB were required for HypA/HypB interaction.
      We further showed that L78A and V80A mutants of HypB failed to reactivate
      hydrogenase in an E. coli DeltahypB strain. Our results suggest that the
      formation of the HypA/HypB complex is essential to the maturation process of
      hydrogenase. The HypA binding site is in proximity to the metal binding site of
      HypB, suggesting that the HypA/HypB interaction may facilitate nickel transfer
      between the two proteins.

PMID- 22384276
TI  - Preventing phosphorylation of sterol regulatory element-binding protein 1a by MAP
      kinases protects mice from fatty liver and visceral obesity.
AB  - The transcription factor sterol regulatory element binding protein (SREBP)-1a
      plays a pivotal role in lipid metabolism. Using the SREBP-1a expressing human
      hepatoma cell line HepG2 we have shown previously that human SREBP-1a is
      phosphorylated at serine 117 by ERK-mitogen-activated protein kinases (MAPK).
      Using a combination of cell biology and protein chemistry approach we show that
      SREBP-1a is also target of other MAPK-families, i.e. c-JUN N-terminal protein
      kinases (JNK) or p38 stress activated MAP kinases. Serine 117 is also the major
      phosphorylation site in SREBP-1a for JNK. In contrast to that the major
      phosphorylation sites of p38 MAPK family are serine 63 and threonine 426.
      Functional analyses reveal that phosphorylation of SREBP-1a does not alter
      protein/DNA interaction. The identified phosphorylation sites are specific for
      both kinase families also in cellular context. To provide direct evidence that
      phosphorylation of SREBP-1a is a regulatory principle of biological and clinical
      relevance, we generated transgenic mice expressing mature transcriptionally
      active N-terminal domain of human SREBP-1a variant lacking all identified
      phosphorylaton sites designed as alb-SREBP-1aDeltaP and wild type SREBP-1a
      designed as alb-SREBP-1a liver specific under control of the albumin promoter and
      a liver specific enhancer. In contrast to alb-SREBP-1a mice the phosphorylation
      deficient mice develop no enlarged fatty livers under normocaloric conditions.
      Phenotypical examination reveales a massive accumulation of adipose tissue in alb
      SREBP-1a but not in the phosphorylation deficient alb-SREBP-1aDeltaP mice.
      Moreover, preventing phosphorylation of SREBP-1a protects mice also from
      dyslipidemia. In conclusion, phosphorylation of SREBP-1a by ERK, JNK and p38 MAPK
      families resembles a biological principle and plays a significant role, in vivo.

PMID- 22384277
TI  - No evidence for pre-copulatory sexual selection on sperm length in a passerine
      bird.
AB  - There is growing evidence that post-copulatory sexual selection, mediated by
      sperm competition, influences the evolution of sperm phenotypes. Evidence for pre
      copulatory sexual selection effects on sperm traits, on the other hand, is rather
      scarce. A recent paper on the pied flycatcher, Ficedula hypoleuca, reported
      phenotypic associations between sperm length and two sexually selected male
      traits, i.e. plumage colour and arrival date, thus invoking pre-copulatory sexual
      selection for longer sperm. We were unable to replicate these associations with a
      larger data set from the same and two additional study populations; sperm length
      was not significantly related to either male plumage colour or arrival date.
      Furthermore, there was no significant difference in sperm length between
      populations despite marked differences in male plumage colour. We also found some
      evidence against the previously held assumption of longer sperm being
      qualitatively superior; longer sperm swam at the same speed as shorter sperm, but
      were less able to maintain speed over time. We argue that both empirical evidence
      and theoretical considerations suggest that the evolution of sperm morphology is
      not primarily associated with pre-copulatory sexual selection on male secondary
      sexual traits in this or other passerine bird species. The relatively large
      between-male variation in sperm length in this species is probably due to relaxed
      post-copulatory sexual selection.

PMID- 22384278
TI  - Biogeographical survey identifies consistent alternative physiological optima and
      a minor role for environmental drivers in maintaining a polymorphism.
AB  - The contribution of adaptive mechanisms in maintaining genetic polymorphisms is
      still debated in many systems. To understand the contribution of selective
      factors in maintaining polymorphism, we investigated large-scale (>1000 km)
      geographic variation in morph frequencies and fitness-related physiological
      traits in the damselfly Nehalennia irene. As fitness-related physiological
      traits, we investigated investment in immune function (phenoloxidase activity),
      energy storage and fecundity (abdomen protein and lipid content), and flight
      muscles (thorax protein content). In the first part of the study, our aim was to
      identify selective agents maintaining the large-scale spatial variation in morph
      frequencies. Morph frequencies varied considerably among populations, but, in
      contrast to expectation, in a geographically unstructured way. Furthermore,
      frequencies co-varied only weakly with the numerous investigated ecological
      parameters. This suggests that spatial frequency patterns are driven by
      stochastic processes, or alternatively, are consequence of highly variable and
      currently unidentified ecological conditions. In line with this, the investigated
      ecological parameters did not affect the fitness-related physiological traits
      differently in both morphs. In the second part of the study, we aimed at
      identifying trade-offs between fitness-related physiological traits that may
      contribute to the local maintenance of both colour morphs by defining alternative
      phenotypic optima, and test the spatial consistency of such trade-off patterns.
      The female morph with higher levels of phenoloxidase activity had a lower thorax
      protein content, and vice versa, suggesting a trade-off between investments in
      immune function and in flight muscles. This physiological trade-off was
      consistent across the geographical scale studied and supports widespread
      correlational selection, possibly driven by male harassment, favouring
      alternative trait combinations in both female morphs.

PMID- 22384279
TI  - Serotonin antagonism improves platelet inhibition in clopidogrel low-responders
      after coronary stent placement: an in vitro pilot study.
AB  - Increased residual platelet reactivity remains a burden for coronary artery
      disease (CAD) patients who received a coronary stent and do not respond
      sufficiently to treatment with acetylsalicylic acid and clopidogrel. We
      hypothesized that serotonin antagonism reduces high on-treatment platelet
      reactivity. Whole blood impedance aggregometry was performed with arachidonic
      acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 uM) in addition to
      different concentrations of serotonin (1-100 uM) in whole blood from 42 CAD
      patients after coronary stent placement and 10 healthy subjects. Serotonin
      increased aggregation dose-dependently in CAD patients who responded to
      clopidogrel treatment: After activation with ADP, aggregation increased from 33.7
      +/- 1.3% to 40.9 +/- 2.0% in the presence of 50 uM serotonin (p<0.05) and to 48.2
      +/- 2.0% with 100 uM serotonin (p<0.001). The platelet serotonin receptor
      antagonist ketanserin decreased ADP-induced aggregation significantly in
      clopidogrel low-responders (from 59.9 +/- 3.1% to 37.4 +/- 3.5, p<0.01), but not
      in clopidogrel responders. These results were confirmed with light transmission
      aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence
      increased residual platelet reactivity in patients who respond to clopidogrel
      after coronary stent placement. In clopidogrel low-responders, serotonin receptor
      antagonism improved platelet inhibition, almost reaching responder levels. This
      may justify further investigation of triple antiplatelet therapy with anti
      serotonergic agents.

PMID- 22384280
TI  - Synapsin II is involved in the molecular pathway of lithium treatment in bipolar
      disorder.
AB  - Bipolar disorder (BD) is a debilitating psychiatric condition with a prevalence
      of 1-2% in the general population that is characterized by severe episodic shifts
      in mood ranging from depressive to manic episodes. One of the most common
      treatments is lithium (Li), with successful response in 30-60% of patients.
      Synapsin II (SYN2) is a neuronal phosphoprotein that we have previously
      identified as a possible candidate gene for the etiology of BD and/or response to
      Li treatment in a genome-wide linkage study focusing on BD patients characterized
      for excellent response to Li prophylaxis. In the present study we investigated
      the role of this gene in BD, particularly as it pertains to Li treatment. We
      investigated the effect of lithium treatment on the expression of SYN2 in
      lymphoblastoid cell lines from patients characterized as excellent Li-responders,
      non-responders, as well as non-psychiatric controls. Finally, we sought to
      determine if Li has a cell-type-specific effect on gene expression in neuronal
      derived cell lines. In both in vitro models, we found SYN2 to be modulated by the
      presence of Li. By focusing on Li-responsive BD we have identified a potential
      mechanism for Li response in some patients.

PMID- 22384281
TI  - Signatures of selection in the genomes of commercial and non-commercial chicken
      breeds.
AB  - Identifying genomics regions that are affected by selection is important to
      understand the domestication and selection history of the domesticated chicken,
      as well as understanding molecular pathways underlying phenotypic traits and
      breeding goals. While whole-genome approaches, either high-density SNP chips or
      massively parallel sequencing, have been successfully applied to identify
      evidence for selective sweeps in chicken, it has been difficult to distinguish
      patterns of selection and stochastic and breed specific effects. Here we present
      a study to identify selective sweeps in a large number of chicken breeds (67 in
      total) using a high-density (58 K) SNP chip. We analyzed commercial chickens
      representing all major breeding goals. In addition, we analyzed non-commercial
      chicken diversity for almost all recognized traditional Dutch breeds and a
      selection of representative breeds from China. Based on their shared history or
      breeding goal we in silico grouped the breeds into 14 breed groups. We identified
      396 chromosomal regions that show suggestive evidence of selection in at least
      one breed group with 26 of these regions showing strong evidence of selection. Of
      these 26 regions, 13 were previously described and 13 yield new candidate genes
      for performance traits in chicken. Our approach demonstrates the strength of
      including many different populations with similar, and breed groups with
      different selection histories to reduce stochastic effects based on single
      populations.

PMID- 22384282
TI  - Deep-sequencing protocols influence the results obtained in small-RNA sequencing.
AB  - Second-generation sequencing is a powerful method for identifying and quantifying
      small-RNA components of cells. However, little attention has been paid to the
      effects of the choice of sequencing platform and library preparation protocol on
      the results obtained. We present a thorough comparison of small-RNA sequencing
      libraries generated from the same embryonic stem cell lines, using different
      sequencing platforms, which represent the three major second-generation
      sequencing technologies, and protocols. We have analysed and compared the
      expression of microRNAs, as well as populations of small RNAs derived from
      repetitive elements. Despite the fact that different libraries display a good
      correlation between sequencing platforms, qualitative and quantitative variations
      in the results were found, depending on the protocol used. Thus, when comparing
      libraries from different biological samples, it is strongly recommended to use
      the same sequencing platform and protocol in order to ensure the biological
      relevance of the comparisons.

PMID- 22384283
TI  - Repeated training with augmentative vibrotactile feedback increases object
      manipulation performance.
AB  - Most users of prosthetic hands must rely on visual feedback alone, which requires
      visual attention and cognitive resources. Providing haptic feedback of variables
      relevant to manipulation, such as contact force, may thus improve the usability
      of prosthetic hands for tasks of daily living. Vibrotactile stimulation was
      explored as a feedback modality in ten unimpaired participants across eight
      sessions in a two-week period. Participants used their right index finger to
      perform a virtual object manipulation task with both visual and augmentative
      vibrotactile feedback related to force. Through repeated training, participants
      were able to learn to use the vibrotactile feedback to significantly improve
      object manipulation. Removal of vibrotactile feedback in session 8 significantly
      reduced task performance. These results suggest that vibrotactile feedback paired
      with training may enhance the manipulation ability of prosthetic hand users
      without the need for more invasive strategies.

PMID- 22384284
TI  - Dairy Consumption, Blood Pressure, and Risk of Hypertension: An Evidence-Based
      Review of Recent Literature.
AB  - Hypertension is a major risk factor for development of stroke, coronary heart
      disease, heart failure, and end-stage renal disease. In a systematic review of
      the evidence published from 2004 to 2009, the 2010 Dietary Guidelines Advisory
      Committee (DGAC) concluded there was moderate evidence of an inverse relationship
      between the intake of milk and milk products (dairy) and blood pressure. This
      review synthesizes results from studies published over the past year on the
      relationship between dairy intake, blood pressure, and hypertension risk. The
      influence of dairy micronutrients including calcium, vitamin D, potassium, and
      phosphorous on blood pressure and incident hypertension is examined. Emerging
      research on bioactive dairy peptides is also reviewed. Lastly, recent evidence on
      effects of dairy fat content on blood pressure and hypertension risk, and the
      impact of inclusion of low-fat dairy in dietary patterns is also investigated.

PMID- 22384285
TI  - The Relationship between Smoking and Depression Post-Acute Coronary Syndrome.
AB  - The purpose of the current paper is to review research on the relationship
      between smoking cessation and depressed mood post-Acute Coronary Syndrome
      (Myocardial infarction or unstable angina; ACS). Emerging evidence regarding the
      effect of anhedonia-a specific subcomponent of mood disturbance characterized by
      reduced pleasure-on post-ACS outcomes is also discussed. There is strong evidence
      that depression prospectively predicts post-ACS relapse to smoking. Weaker
      evidence suggests that smoking at the time of ACS is related to post-ACS
      depression. Bupropion is a particularly promising treatment for this population
      because of its smoking cessation and anti-depressant effects. Future research
      should focus on the relative risk of using nicotine replacement therapies post
      ACS, the efficacy of bupropion for smoking cessation and depression reduction in
      post-ACS patients, the role of anhedonia in post-ACS smoking cessation, and the
      development and testing of integrated behavioral treatments (smoking cessation
      plus interventions targeting mood management) for ACS patients.

PMID- 22384286
TI  - Mortality associated with cardiovascular diseases in three hospitals of Lome
      city.
AB  - The aims of present study were; to determine the mortality rate related to
      cardiovascular diseases and the causes of those deaths in local hospitals. We
      conducted a cross sectional study carried out from January 2005 to June 2006, in
      three hospitals of Lome. All deaths registered in the departments of cardiology
      and neurology from cardiovascular diseases were taken into account. The number of
      patients who died from cardiovascular diseases was 200 on 2386 admitted patients
      (11.86%). The average age was 54.4 +/- 15.6 years (range: 18-102).
      Cerebrovascular stroke was the most represented disease (56.9%), followed by
      heart failure (35.7%), and cardiac arrhythmias (15.9%). Hospital mortality due to
      cardiovascular afflictions was high in Lome-city due to the deficient
      organization of the cardiovascular resuscitation units. Better organization, more
      equipment for cardiovascular care units and better public health efforts
      surrounding control of cardiovascular risk factors could go a long way towards
      the reduction of this high mortality rate of cardiovascular diseases in our
      hospitals.

PMID- 22384287
TI  - Mesenteric dermoid cyst in a child.
AB  - If a pediatric abdominal mass is not organomegaly or colonic stool, narrowing the
      diagnostic possibilities may be difficult, especially in resource-poor areas
      where ancillary tests and treatment options may be limited. A 2-year-old girl was
      brought to the rural Kintampo Municipal Hospital in Ghana with a freely moveable,
      non-tender abdominal mass. A huge mesenteric dermoid cyst was surgically removed.
      Mesenteric cysts are rare intra-abdominal lesions, most commonly occurring in
      children <10 years old. Making a preoperative diagnosis is difficult. Dermoid
      cysts (mature cystic teratoma) rarely occur in the mesentery. Poverty, family
      circumstances and the rural location led to general physicians doing surgery. As
      in this case, due to economic, social and transportation issues common throughout
      Africa, children with abdominal masses may need at least initial surgery in
      hospitals without dedicated pediatric surgery or even a trained surgeon.

PMID- 22384288
TI  - [Congenital syphilis revealed by a spontaneous fracture].

PMID- 22384289
TI  - [Hydatid cysts of the liver ruptured into the biliary tracts: report of 120
      cases].

PMID- 22384290
TI  - [Splenic metastasis from colonic adenocarcinoma - about a case and literature
      review].

PMID- 22384291
TI  - [Depression and level of burden among family caregivers of demented patients in
      Tunisia].

PMID- 22384292
TI  - Malaria complicated by gangrene: a case presentation and review.
AB  - Symmetrical peripheral gangrene (SPG) is an extremely rare complication of
      malaria. It occurs acutely and progresses rapidly to cause irreversible necrosis
      of tissue following which debridement or amputation is inevitable. We present a
      case of malaria complicated by SPG. A 54-year old male developed SPG two days
      after he was diagnosed with severe malaria and treated with intravenous quinine.
      Despite intervention quad-amputation was necessary as the gangrene had involved
      all four limbs. SPG secondary to malaria is caused by obstruction of arterioles
      following sequestration of parasite infected erythrocytes. This is extremely
      rare, hence almost never anticipated during management of malaria patients.
      Furthermore due to its rapid progression, it is almost always detected at an
      advanced irreversible stage. Physicians managing malaria should therefore be
      vigilant, and look out for SPG, as its prognosis is dependent on correct and
      timely intervention.

PMID- 22384293
TI  - Risk factors for non-communicable diseases in rural Uganda: a pilot surveillance
      project among diabetes patients at a referral hospital clinic.
AB  - INTRODUCTION: Despite an increasing recognition of non- communicable diseases
      (NCDs) in sub-Saharan Africa, there is lack of well established surveillance
      systems for these diseases. In an effort to understand burden of NCDs in low
      resource settings, the African Field Epidemiology Network launched a pilot
      project in 2009 to routinely capture patient data in the diabetes clinic of
      Mbarara Regional Referral Hospital. The objective of this study was to determine
      the prevalence and, the gender- and age- specific distributions of common NCD
      risk factors among diabetic patients attending a referral hospital in rural
      Uganda. METHODS: A relational Access database was designed to collect information
      on NCD risk factors. These included smoking, alcohol use, family history of
      diabetes, hypertension and body mass index. Univariate analyses were done and
      differences in proportions tested using chi-square P-values in STATA version
      10.0. RESULTS: A total of 1,383 patient records were analyzed, with 61% being
      female and mean age of 39.6 years (SD 15.8). About 24% had a family history of
      diabetes. Smoking and alcohol use were more prevalent among males (16.6% vs.
      8.3%; p<0.0001) and (30.7 vs. 13%; p<0.0001) respectively. Overweight, obesity
      and hypertension were more prevalent in women (18.6% vs. 9.7%, 8.6% vs. 2.6%;
      p<0.0001, and 40.3% vs. 33%, p=0.018) respectively. CONCLUSION: This pilot
      project shows that use of hospital-based data is a valuable initial step in
      setting up surveillance systems for NCDs in Uganda. Risk factors for NCDs were
      both age and gender-specific and predominantly related to lifestyle. This
      suggests the need to design gender-sensitive prevention interventions that target
      lifestyle modification in this setting.

PMID- 22384295
TI  - [An exceptional tumor of the finger: the solitary fibrous tumor].

PMID- 22384294
TI  - Microbial keratitis in Gujarat, Western India: findings from 200 cases.
AB  - INTRODUCTION: The objective of this study was to study the epidemiological
      characteristics and the microbiological profile of patients suspected with
      microbial keratitis in Gujarat. METHODS: Corneal scraping was collected from 200
      consecutive cases of suspected microbial keratitis and was subjected to direct
      examination and culture. RESULTS: Of the 200 ulcers 55% were culture positive,
      26.5% were bacterial ulcers of which 47% were due to Staphylococcus spp. Pure
      fungal growth was seen in 22% while 6% were mixed ulcers. Fusarium spp. (30%) was
      the most common fungus followed by Aspergillus spp. (21%). Only one case of
      Acanthamoeba keratitis was encountered. Patients were mainly from rural areas
      (61.5%) with male preponderance (61.5%). Corneal injury was seen in 78.5% cases
      of which 53% had injury with vegetative matter. Prior treatment was seen in 58%
      of which 5% had been treated by village healers. Nineteen patients (9.5%) also
      used some kind of traditional topical treatment. Increased incidence was seen
      from August to December. Five case of fugal ulcers lead to perforation of which
      three were due to Fusarium spp. whereas perforation was seen in only two cases of
      bacterial ulcers due to Pseudomonas aeruginosa. CONCLUSION: Staphylococcus and
      Fusarium spp. were the most common etiological agents in our region. Predominant
      outdoor agricultural activity is the principal causative factor for corneal
      injury. Corneal ulcers complicated due to treatment by village healers are
      another important concern. The information regarding regional etiology will help
      empirical management as many eye clinics do not have microbiological facilities.

PMID- 22384296
TI  - [Transanal evisceration of the small intestine in a child secondary to blunt
      trauma to the abdomen: report of a case].

PMID- 22384297
TI  - [A rectovaginal fistula within the scope of a Currarino syndrome].

PMID- 22384298
TI  - Diagnostic evaluation of primary cervical adenopathies in a developing country.
AB  - INTRODUCTION: To review the pathology of lymph node biopsies removed from
      patients with primary cervical lymphadenopathy. METHODS: A 20 (1987-2006) year
      retrospective study of all patients who had lymph node biopsy; in the Department
      of Pathology and Haematology, University of Benin Teaching Hospital, Benin City,
      Nigeria. RESULTS: Of 357 lymph node biopsies accessioned, 68 (19.0%) cases were
      in children. Granulomatous diseases constituted 128 (35.9%) cases. Tuberculosis
      (Tb) was the single commonest cause of cervical lymphadenopathy constituting 125
      (35.0%) cases and also the commonest cause of cervical lymphadenopathy below the
      age of 45 years. Tuberculosis (TB) lymphadenopathy occurred predominantly in male
      children and young female adults. TB lymphadenopathy was rare above the age of 45
      years. Neoplastic diseases constituted 173 (48.5%) cases. Of these, lymphoma
      predominated comprising 93 (26.1%) cases. These included 37 (10.4%) and 56
      (15.7%) cases of Hodgkin?s lymphoma and non Hodgkin?s lymphoma respectively.
      Hodgkin?s lymphoma occurred most commonly in young male adults. Metastatic
      tumours constituted 80 (22.4%) cases and was the predominant cause of cervical
      lymphadenopathy above the age of 45 years. Non specific reactive lymphadenitis
      constituted 56 (15.7%) cases. CONCLUSION: Chronic lymphadenopathy in our
      environment has a high incidence of tuberculosis. We recommend urgent lymph node
      biopsy in significantly enlarged nodes not responding to treatment.

PMID- 22384299
TI  - Contraception awareness and practice among antenatal attendees in Uyo, Nigeria.
AB  - INTRODUCTION: Contraception is major component of reproductive health. The study
      aims to document the awareness of contraception and its use in Uyo, South-south
      Nigeria and provide useful information for future intervention strategies.
      METHODS: A cross-sectional study using pretested questionnaires among antenatal
      attendees in a tertiary and a secondary health facility in Uyo. RESULTS: A total
      of 550 women took part in the study. Majority of respondents (92.4%) were aware
      of contraception while 52.6% had ever used any form of contraception. The condom
      (60.3%) and the pill (49.9%) were the most common forms of contraception that the
      women had heard of, mostly from the doctor (36.9%), radio (33.8%) and nurse
      (28.5%). The condom (46.7%), withdrawal method (14.1%) and the pills (13.3%) were
      the most commonly used forms of contraception. Majority of the women (70.5%)
      planned to use contraception in the future and this intention was significantly
      related to the woman's educational status (p<0.05) but not to religion or
      occupation. Fear of side effects, uncertainty about its need, partner objection
      and previous side effects were the common reasons given for unwillingness to use
      contraception in the future. CONCLUSION: Our study has shown that while there is
      good contraceptive awareness in Uyo, Nigeria, this is not matched by commensurate
      contraceptive prevalence but prospects for improvement exist. There's need to
      tackle known obstacles to contraceptive uptake. Also targeted campaigns and every
      available opportunity should be used to provide reproductive counseling to women
      especially on contraception.

PMID- 22384300
TI  - Epidemiological characteristics of pandemic influenza A (H1N1-2009) in Zhanjiang,
      China.
AB  - BACKGROUND: A novel influenza A virus strain (H1N1-2009) spread first in Mexico
      and the United Stated in late April 2009, leading to the first influenza pandemic
      of the 21(st) century. The objective of this study was to determine the
      epidemiological and virological characteristics of the pandemic influenza A (H1N1
      2009) in Zhanjiang, China. METHODS: The case and outbreak reports of influenza
      like illness (ILI) were collected from the Chinese information system of disease
      control and prevention and the influenza surveillance system of Zhanjiang city.
      Real-time RT-PCR was conducted, and epidemic and virological characteristics of
      the virus were analyzed using descriptive epidemiological methods and Chi-square
      trend tests. RESULTS: A total of 276 reported cases were confirmed from July 16,
      2009 to June 30, 2010. The attack rate of outbreak was from 1.1% to 6.0%. The
      disease peak occurred in December 2009, after which the outbreak subsided
      gradually. The last case was confirmed in April 2010. CONCLUSION: The main
      population struck by the H1N1-2009 virus was young adults, youths and children.
      The outbreaks most frequently occurred in schools, and most cases were acquired
      locally.

PMID- 22384301
TI  - Health worker migration and universal health care in Sub-Saharan Africa.
AB  - There is a more and more emerging consensus claiming universal access to health
      care in order to achieve the desired Millennium Development Goals related to
      health in Africa. Unfortunately, the debate of the universal coverage has
      focussed so far mainly on financial affordability, while it is also a human
      resource matter. Many countries in sub-Saharan Africa are experiencing severe
      shortages of skilled health care workers. There are several causes, the
      importance of which varies by country, but one of the most significant factors is
      brain drain. In those countries, scarcity of doctors increases the distance
      between a doctor and patients, and bridging that increased distance implies
      costs, both time and money. Adequate number of qualified health personnel is then
      vital to increase coverage and improve the quality of care. In as much as access
      to health services is also determined by access to qualified health workers, any
      reflection on the universal health coverage has to also consider the inequities
      in qualified health personnel distribution throughout the world.

PMID- 22384302
TI  - A rare cause of proximal intestinal obstruction in adults - annular pancreas: a
      case report.
AB  - Annular pancreas is a rare congenital anomaly characterized by the presence of
      ectopic pancreatic tissue surrounding the descending part of the duodenum. It is
      one of the few congenital anomalies of the gastrointestinal tract which can
      produce symptoms late in life. In adults, the factors initiating symptoms are
      recurrent pancreatitis, duodenal stenosis at the site of the annulus, or duodenal
      or gastric ulceration. We report a new case involving a 24-year-old woman
      hospitalised for epigastric pain, nausea and vomiting. Radiological examination
      was consisted with an annular pancreas. At operation a complete obstruction of
      the second part of the duodenum was found, caused by an annular pancreas, no
      other congenital anomaly of the intra-abdominal organs was noted. A
      gastroenterostomy was performed.

PMID- 22384303
TI  - Intussusception caused by an inverted Meckel's diverticulum: a rare cause of
      small bowel obstruction in adults.
AB  - Adult intussusception due to Meckel's diverticulum is an uncommon cause of
      intestinal obstruction. However, the surgeon should still be suspicious of this
      condition since the non specific symptoms and the rarity of it make a
      preoperative diagnosis uncertain. Considering the secondary nature of adult
      intussusception and the necessity of early surgical intervention to avoid
      morbidity and mortality, we report one case of intussusception due to Meckel's
      diverticulum in an adult. A 22-year-old patient was admitted to our hospital with
      vomiting and abdominal pain. The abdomen was hard with tenderness. We diagnosed
      an acute small bowel obstruction and performed emergency surgery. The intra
      operative findings were distention of the small bowel and intussusception of
      ileus due to an inverted Meckel's diverticulum located 70 cm from the ileocecal
      valve. 30 cm ischemic loop was identified. A segmental small bowel resection and
      hand-sewn anastomosis was performed. Histopathology distinguished Meckel's
      diverticulum measuring 5 cm x 3.5 cm x 1 cm and no signs of malignancy.

PMID- 22384304
TI  - [The hydatid cyst of the spermatic cord: an exceptional localization].

PMID- 22384305
TI  - [Quality of certificates of assault and battery on adults in Dakar and Diourbel,
      Senegal].

PMID- 22384306
TI  - [Neonatal hypertrophic cardiomyopathy of difficult etiologic diagnosis].

PMID- 22384307
TI  - [Glanzmann's thrombasthenia and pregnancy: report of a case and literature
      review].

PMID- 22384308
TI  - Exercise Training Prevents Coronary Endothelial Dysfunction in Type 2 Diabetic
      Mice.
AB  - Type 2 diabetes (T2D) is a leading risk factor for cardiovascular diseases
      including atherosclerosis and coronary heart disease. Exercise training (ET) is
      thought to have a beneficial effect on these disorders, but the basis for this
      effect is not fully understood. Because endothelial dysfunction plays a key role
      in the pathological events leading to cardiovascular complications in T2D, we
      hypothesized that the effects of ET will be evidenced by improvements in coronary
      endothelial function. To test this hypothesis, we assessed the effects of ET on
      vascular function of diabetic (db/db, Lepr(db)) mice by evaluating endothelial
      function of isolated coronary arterioles of wild-type (WT) and db/db mice
      with/without ET. Although dilation of vessels to the endothelial-independent
      vasodilator, sodium nitroprusside was not different between db/db and WT,
      dilation to the endothelial-dependent agonist, acetylcholine (ACh), was impaired
      in db/db compared to WT mice. Vasodilation to ACh was restored in db/db with ET
      and insulin sensitivity was improved in the db/db after ET. Exercise did not
      change body weight of db/db, but superoxide dismutase (SOD1 and SOD2) and
      phosphorylated- eNOS protein (Ser1177) expression in heart tissue was up
      regulated whereas tumor necrosis factor-alpha (TNF-alpha) protein level was
      decreased by ET. Serum level of interleukin-6 (IL-6) was higher in db/db mice but
      ET decreased IL-6. This suggests that ET may improve endothelial function by
      increasing nitric oxide bioavailability as well as decreasing chronic
      inflammation. We suggest this connection may be the basis for the benefit of ET
      in T2D.

PMID- 22384309
TI  - A Still-face Paradigm for Young Children: 21/2 Year-olds' Reactions to Maternal
      Unavailability during the Still-face.
AB  - This study evaluated similarities and differences in 21/2 year-old children's
      reactions to maternal unavailability during a brief still-face episode and
      subsequent resumption of social interaction during a reunion episode. Seventy
      mothers and children were videotaped in the Toddler Still-Face paradigm (T-SF),
      an age appropriate adaptation of the Face-to-Face Still-Face paradigm. Similar to
      their younger counterparts, 21/2 year-olds displayed the traditional "still-face
      effect," including an increase in negative affect, gaze aversion, and a wide
      array of behaviors indicative of proximity seeking to the mother, solicitation of
      her attention, and avoidance and a "reunion effect," characterized by a carryover
      of negative affect and avoidance behavior (e.g., moving away from the mother)
      from the still-face episode to the reunion play episode. However, differences in
      toddlers' behaviors during the still-face and reunion episodes were also
      observed, which highlight age-related changes in the toddlers' ability to cope
      with the stress of maternal unavailability during the still-face during the third
      year of life. Contrary to reports for younger infants, few gender differences
      were found in toddlers' reactions to the still-face. The findings support the
      hypothesis that the toddlers are attempting to make meaning out of an unexpected
      and senseless event.

PMID- 22384310
TI  - Diamine Ligands in Copper-Catalyzed Reactions.
AB  - The utility of copper-mediated cross-coupling reactions has been significantly
      increased by the development of mild reaction conditions and the ability to
      employ catalytic amounts of copper. The use of diamine-based ligands has been
      important in these advances and in this review we discuss these systems,
      including the choice of reaction conditions and applications in the synthesis of
      pharmaceuticals, natural products and designed materials.

PMID- 22384311
TI  - Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with
      Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases.
AB  - We report our studies on the use of two catalyst systems, based on the ligands
      BrettPhos (1) and RuPhos (2), which provide the widest scope for Pd-catalyzed C-N
      cross-coupling reactions to date. Often low catalyst loadings and short reaction
      times can be used with functionalized aryl and heteroaryl coupling partners. The
      reactions are highly robust and can be set up and performed without the use of a
      glovebox. These catalysts should find wide application in the synthesis of
      complex molecules including pharmaceuticals, natural products and functional
      materials.

PMID- 22384313
TI  - GSA Launches G3: Genes | Genomes | Genetics.

PMID- 22384312
TI  - Src inhibitors in the treatment of metastatic bone disease: rationale and
      clinical data.
AB  - Src is a nonreceptor tyrosine kinase essential for the activation of osteoclasts,
      the cells that degrade bone. Src also regulates normal cell functions, cancer
      cell growth and metastasis to organs, including bone where tumor cells induce
      bone destruction by osteoclasts. Src inhibitors prevent bone destruction and
      tumor cell growth in animal models of metastatic bone disease, and some are being
      investigated in clinical trials, particularly in patients with prostate cancer,
      which has high bone metastatic potential. Here, we review how Src regulates
      osteoclast formation, activation and survival and the results of preclinical and
      clinical trials of Src inhibitors, which show some promise in inhibiting the
      effects of tumor cells on the skeleton.

PMID- 22384315
TI  - Variability of Gene Expression After Polyhaploidization in Wheat (Triticum
      aestivum L.).
AB  - Interspecific hybridization has a much greater effect than chromosome doubling on
      gene expression; however, the associations between homeologous gene expression
      changes and polyhaploidization had rarely been addressed. In this study, cDNA
      single strand conformation polymorphism analysis was applied to measure the
      expression of 30 homeologous transcripts in naturally occurring haploid (ABD, 2n
      = 21) and its polyploid maternal parent Yumai 21A (AABBDD, 2n = 42) in wheat.
      Only one gene (TC251989) showed preferentially silenced homoeoalleles in
      haploids. Further analyses of 24 single-copy genes known to be silenced in the
      root and/or leaf also found no evidence of homeologous silencing in 1-month-old
      haploids and two ESTs (BF484100 and BF473379) exhibit different expression
      patterns between 4-month-old haploids and hexaploids. Global analysis of the gene
      expression patterns using the Affymetrix GeneChip showed that of the 55,052 genes
      probed, only about 0.11% in the shoots and 0.25% in the roots were activated by
      polyhaploidization. The results demonstrate that activation and silencing of
      homoeoalleles were not widespread in haploid seedlings.

PMID- 22384314
TI  - The Awesome Power of Yeast Evolutionary Genetics: New Genome Sequences and Strain
      Resources for the Saccharomyces sensu stricto Genus.
AB  - High-quality, well-annotated genome sequences and standardized laboratory strains
      fuel experimental and evolutionary research. We present improved genome sequences
      of three species of Saccharomyces sensu stricto yeasts: S. bayanus var. uvarum
      (CBS 7001), S. kudriavzevii (IFO 1802(T) and ZP 591), and S. mikatae (IFO
      1815(T)), and describe their comparison to the genomes of S. cerevisiae and S.
      paradoxus. The new sequences, derived by assembling millions of short DNA
      sequence reads together with previously published Sanger shotgun reads, have
      vastly greater long-range continuity and far fewer gaps than the previously
      available genome sequences. New gene predictions defined a set of 5261 protein
      coding orthologs across the five most commonly studied Saccharomyces yeasts,
      enabling a re-examination of the tempo and mode of yeast gene evolution and
      improved inferences of species-specific gains and losses. To facilitate
      experimental investigations, we generated genetically marked, stable haploid
      strains for all three of these Saccharomyces species. These nearly complete
      genome sequences and the collection of genetically marked strains provide a
      valuable toolset for comparative studies of gene function, metabolism, and
      evolution, and render Saccharomyces sensu stricto the most experimentally
      tractable model genus. These resources are freely available and accessible
      through www.SaccharomycesSensuStricto.org.

PMID- 22384316
TI  - Inferring haplotypes of copy number variations from high-throughput data with
      uncertainty.
AB  - Accurate information on haplotypes and diplotypes (haplotype pairs) is required
      for population-genetic analyses; however, microarrays do not provide data on a
      haplotype or diplotype at a copy number variation (CNV) locus; they only provide
      data on the total number of copies over a diplotype or an unphased sequence
      genotype (e.g., AAB, unlike AB of single nucleotide polymorphism). Moreover, such
      copy numbers or genotypes are often incorrectly determined when microarray signal
      intensities derived from different copy numbers or genotypes are not clearly
      separated due to noise. Here we report an algorithm to infer CNV haplotypes and
      individuals' diplotypes at multiple loci from noisy microarray data, utilizing
      the probability that a signal intensity may be derived from different underlying
      copy numbers or genotypes. Performing simulation studies based on known
      diplotypes and an error model obtained from real microarray data, we demonstrate
      that this probabilistic approach succeeds in accurate inference (error rate: 1
      2%) from noisy data, whereas previous deterministic approaches failed (error
      rate: 12-18%). Applying this algorithm to real microarray data, we estimated
      haplotype frequencies and diplotypes in 1486 CNV regions for 100 individuals. Our
      algorithm will facilitate accurate population-genetic analyses and powerful
      disease association studies of CNVs.

PMID- 22384318
TI  - An Improved Method for Estimating Chromosomal Line Origin in QTL Analysis of
      Crosses Between Outbred Lines.
AB  - Estimating the line origin of chromosomal sections from marker genotypes is a
      vital step in quantitative trait loci analyses of outbred line crosses. The
      original, and most commonly used, algorithm can only handle moderate numbers of
      partially informative markers. The advent of high-density genotyping with SNP
      chips motivates a new method because the generic sets of markers on SNP chips
      typically result in long stretches of partially informative markers. We validated
      a new method for inferring line origin, triM (tracing inheritance with Markov
      models), with simulated data. A realistic pattern of marker information was
      achieved by replicating the linkage disequilibrium from an existing chicken
      intercross. There were approximately 1500 SNP markers and 800 F(2) individuals.
      The performance of triM was compared to GridQTL, which uses a variant of the
      original algorithm but modified for larger datasets. triM estimated the line
      origin with an average error of 2%, was 10% more accurate than GridQTL,
      considerably faster, and better at inferring positions of recombination. GridQTL
      could not analyze all simulated replicates and did not estimate line origin for
      around a third of individuals at many positions. The study shows that triM has
      computational benefits and improved estimation over available algorithms and is
      valuable for analyzing the large datasets that will be standard in future.

PMID- 22384317
TI  - Identification of yeast genes involved in k homeostasis: loss of membrane traffic
      genes affects k uptake.
AB  - Using the homozygous diploid Saccharomyces deletion collection, we searched for
      strains with defects in K(+) homeostasis. We identified 156 (of 4653 total)
      strains unable to grow in the presence of hygromycin B, a phenotype previously
      shown to be indicative of ion defects. The most abundant group was that with
      deletions of genes known to encode membrane traffic regulators. Nearly 80% of
      these membrane traffic defective strains showed defects in uptake of the K(+)
      homolog, (86)Rb(+). Since Trk1, a plasma membrane protein localized to lipid
      microdomains, is the major K(+) influx transporter, we examined the subcellular
      localization and Triton-X 100 insolubility of Trk1 in 29 of the traffic mutants.
      However, few of these showed defects in the steady state levels of Trk1, the
      localization of Trk1 to the plasma membrane, or the localization of Trk1 to lipid
      microdomains, and most defects were mild compared to wild-type. Three inositol
      kinase mutants were also identified, and in contrast, loss of these genes
      negatively affected Trk1 protein levels. In summary, this work reveals a nexus
      between K(+) homeostasis and membrane traffic, which does not involve traffic of
      the major influx transporter, Trk1.

PMID- 22384319
TI  - Fine Mapping of a QTL for Fertility on BTA7 and Its Association With a CNV in the
      Israeli Holsteins.
AB  - A quantitative trait locus (QTL) affecting female fertility, scored as the
      inverse of the number of inseminations to conception, on Bos taurus chromosome 7
      was detected by a daughter design analysis of the Israeli Holstein population (P
      < 0.0003). Sires of five of the 10 families analyzed were heterozygous for the
      QTL. The 95% confidence interval of the QTL spans 27 cM from the centromere.
      Seven hundred and four SNP markers on the Illumina BovineSNP50 BeadChip within
      the QTL confidence interval were tested for concordance. A single SNP, NGS-58779,
      was heterozygous for all the five QTL heterozygous patriarchs, and homozygous for
      the remaining five QTL homozygous sires. A significant effect on fertility was
      associated with this marker in the sample of 900 sires genotyped (P < 10(-6)).
      Haplotype phase was the same for four of the five segregating sires. Thus
      concordance was obtained in nine of the ten families. We identified a common
      haplotype region associated with the rare and economically favorable allele of
      the SNP, spanning 270 kbp on BTA7 upstream to 4.72 Mbp. Eleven genes found in the
      common haplotype region should be considered as positional candidates for the
      identification of the causative quantitative trait nucleotide. Copy number
      variation was found in one of these genes, KIAA1683. Four gene variants were
      identified, but only the number of copies of a specific variant (V(1)) was
      significantly associated with breeding values of sires for fertility.

PMID- 22384320
TI  - Identification of epigenetic regulators of a transcriptionally silenced transgene
      in maize.
AB  - Transcriptional gene silencing is a gene regulatory mechanism essential to all
      organisms. Many transcriptional regulatory mechanisms are associated with
      epigenetic modifications such as changes in chromatin structure, acetylation and
      methylation of core histone proteins, and DNA methylation within regulatory
      regions of endogenous genes and transgenes. Although several maize mutants have
      been identified from prior forward genetic screens for epigenetic transcriptional
      silencing, these screens have been far from saturated. Herein, the
      transcriptionally silent b1 genomic transgene (BTG-silent), a stable,
      epigenetically silenced transgene in Zea mays (maize), is demonstrated to be an
      effective phenotype for a forward genetic screen. When the transgene is
      reactivated, a dark purple plant phenotype is evident because the B1
      transcription factor activates anthocyanin biosynthesis, making loss of silencing
      mutants easy to identify. Using BTG-silent, ten new putative mutants were
      identified and named transgene reactivated1 through 11 (tgr1-6 and tgr8-11).
      Three of these mutants have been examined in more detail, and molecular and
      genetic assays demonstrated that these mutants have both distinct and overlapping
      phenotypes with previously identified maize mutants that relieve epigenetic
      transcriptional silencing. Linkage analysis suggests that tgr2 and tgr3 do not
      correspond to a mutation at previously identified maize loci resulting from other
      forward genetic screens, while tgr1 shows linkage to a characterized gene. These
      results suggest that the mutants are a valuable resource for future studies
      because some of the mutants are likely to reveal genes that encode products
      required for epigenetic gene regulation in maize but are not currently
      represented by sequenced mutations.

PMID- 22384321
TI  - Organization and evolution of subtelomeric satellite repeats in the potato
      genome.
AB  - Subtelomeric domains immediately adjacent to telomeres represent one of the most
      dynamic and rapidly evolving regions in eukaryotic genomes. A common feature
      associated with subtelomeric regions in different eukaryotes is the presence of
      long arrays of tandemly repeated satellite sequences. However, studies on
      molecular organization and evolution of subtelomeric repeats are rare. We
      isolated two subtelomeric repeats, CL14 and CL34, from potato (Solanum
      tuberosum). The CL14 and CL34 repeats are organized as independent long arrays,
      up to 1-3 Mb, of 182 bp and 339 bp monomers, respectively. The CL14 and CL34
      repeat arrays are directly connected with the telomeric repeats at some
      chromosomal ends. The CL14 repeat was detected at the subtelomeric regions among
      highly diverged Solanum species, including tomato (Solanum lycopersicum). In
      contrast, CL34 was only found in potato and its closely related species.
      Interestingly, the CL34 repeat array was always proximal to the telomeres when
      both CL14 and CL34 were found at the same chromosomal end. In addition, the CL34
      repeat family showed more sequence variability among monomers compared with the
      CL14 repeat family. We conclude that the CL34 repeat family emerged recently from
      the subtelomeric regions of potato chromosomes and is rapidly evolving. These
      results provide further evidence that subtelomeric domains are among the most
      dynamic regions in eukaryotic genomes.

PMID- 22384322
TI  - Translational Genomics in Legumes Allowed Placing In Silico 5460 Unigenes on the
      Pea Functional Map and Identified Candidate Genes in Pisum sativum L.
AB  - To identify genes involved in phenotypic traits, translational genomics from
      highly characterized model plants to poorly characterized crop plants provides a
      valuable source of markers to saturate a zone of interest as well as functionally
      characterized candidate genes. In this paper, an integrated view of the pea
      genetic map was developed. A series of gene markers were mapped and their best
      reciprocal homologs were identified on M. truncatula, L. japonicus, soybean, and
      poplar pseudomolecules. Based on the syntenic relationships uncovered between pea
      and M. truncatula, 5460 pea Unigenes were tentatively placed on the consensus
      map. A new bioinformatics tool,
      http://www.thelegumeportal.net/pea_mtr_translational_toolkit, was developed that
      allows, for any gene sequence, to search its putative position on the pea
      consensus map and hence to search for candidate genes among neighboring Unigenes.
      As an example, a promising candidate gene for the hypernodulation mutation nod3
      in pea was proposed based on the map position of the likely homolog of Pub1, a M.
      truncatula gene involved in nodulation regulation. A broader view of pea genome
      evolution was obtained by revealing syntenic relationships between pea and
      sequenced genomes. Blocks of synteny were identified which gave new insights into
      the evolution of chromosome structure in Papillionoids and Eudicots. The power of
      the translational genomics approach was underlined.

PMID- 22384323
TI  - A QTL Study for Regions Contributing to Arabidopsis thaliana Root Skewing on
      Tilted Surfaces.
AB  - Plant root systems must grow in a manner that is dictated by endogenous genetic
      pathways, yet sensitive to environmental input. This allows them to provide the
      plant with water and nutrients while navigating a heterogeneous soil environment
      filled with obstacles, toxins, and pests. Gravity and touch, which constitute
      important cues for roots growing in soil, have been shown to modulate root
      architecture by altering growth patterns. This is illustrated by Arabidopsis
      thaliana roots growing on tilted hard agar surfaces. Under these conditions, the
      roots are exposed to both gravity and touch stimulation. Consequently, they tend
      to skew their growth away from the vertical and wave along the surface. This
      complex growth behavior is believed to help roots avoid obstacles in nature.
      Interestingly, A. thaliana accessions display distinct growth patterns under
      these conditions, suggesting the possibility of using this variation as a tool to
      identify the molecular mechanisms that modulate root behavior in response to
      their mechanical environment. We have used the Cvi/Ler recombinant inbred line
      population to identify quantitative trait loci that contribute to root skewing on
      tilted hard agar surfaces. A combination of fine mapping for one of these QTL and
      microarray analysis of expression differences between Cvi and Ler root tips
      identifies a region on chromosome 2 as contributing to root skewing on tilted
      surfaces, potentially by modulating cell wall composition.

PMID- 22384324
TI  - Fluorescence in situ hybridization-based karyotyping of soybean translocation
      lines.
AB  - Soybean (Glycine max [L.] Merr.) is a major crop species and, therefore, a major
      target of genomic and genetic research. However, in contrast to other plant
      species, relatively few chromosomal aberrations have been identified and
      characterized in soybean. This is due in part to the difficulty of cytogenetic
      analysis of its small, morphologically homogeneous chromosomes. The recent
      development of a fluorescence in situ hybridization -based karyotyping system for
      soybean has enabled our characterization of most of the chromosomal translocation
      lines identified to date. Utilizing genetic data from existing translocation
      studies in soybean, we identified the chromosomes and approximate breakpoints
      involved in five translocation lines.

PMID- 22384325
TI  - Quantitative genetics of genomic imprinting: a comparison of simple variance
      derivations, the effects of inbreeding, and response to selection.
AB  - The level of expression of an imprinted gene is dependent on the sex of the
      parent from which it was inherited. As a result, reciprocal heterozygotes in a
      population may have different mean phenotypes for quantitative traits. Using
      standard quantitative genetic methods for deriving breeding values, population
      variances, and covariances between relatives, we demonstrate that although these
      approaches are equivalent under Mendelian expression, this equivalence is lost
      when genomic imprinting is acting. Imprinting introduces both parent-of-origin
      dependent and generation-dependent effects that result in differences in the way
      additive and dominance effects are defined for the various approaches. Further,
      imprinting creates a covariance between additive and dominance terms absent under
      Mendelian expression, but the expression for this covariance cannot be derived
      using a number of the standard approaches for defining additive and dominance
      terms. Inbreeding also generates such a covariance, and we demonstrate that a
      modified method for partitioning variances can easily accommodate both inbreeding
      and imprinting. As with inbreeding, the concept of breeding values has no useful
      meaning for an imprinted trait. Finally, we derive the expression for the
      response to selection under imprinting, and conclude that the response to
      selection for an imprinted trait cannot be predicted from the breeder's equation,
      even when there is no dominance.

PMID- 22384326
TI  - A Screen for Germination Mutants in Saccharomyces cerevisiae.
AB  - Spore germination in Saccharomyces cerevisiae is a process in which a quiescent
      cell begins to divide. During germination, the cell undergoes dramatic changes in
      cell wall and membrane composition, as well as in gene expression. To understand
      germination in greater detail, we screened the S. cerevisiae deletion set for
      germination mutants. Our results identified two genes, TRF4 and ERG6, that are
      required for normal germination on solid media. TRF4 is a member of the TRAMP
      complex that, together with the exosome, degrades RNA polymerase II transcripts.
      ERG6 encodes a key step in ergosterol biosynthesis. Taken together, these results
      demonstrate the complex nature of germination and two genes important in the
      process.

PMID- 22384327
TI  - Genetic Variation in the Chemical Components of Eucalyptus globulus Wood.
AB  - Despite the ecological and economic importance of lignin and other wood chemical
      components, there are few studies of the natural genetic variation that exists
      within plant species and its adaptive significance. We used models developed from
      near infra-red spectroscopy to study natural genetic variation in lignin content
      and monomer composition (syringyl-to-guaiacyl ratio [S/G]) as well as cellulose
      and extractives content, using a 16-year-old field trial of an Australian tree
      species, Eucalyptus globulus. We sampled 2163 progenies of 467 native trees from
      throughout the native geographic range of the species. The narrow-sense
      heritability of wood chemical traits (0.25-0.44) was higher than that of growth
      (0.15), but less than wood density (0.51). All wood chemical traits exhibited
      significant broad-scale genetic differentiation (Q(ST) = 0.34-0.43) across the
      species range. This differentiation exceeded that detected with putatively
      neutral microsatellite markers (F(ST) = 0.09), arguing that diversifying
      selection has shaped population differentiation in wood chemistry. There were
      significant genetic correlations among these wood chemical traits at the
      population and additive genetic levels. However, population differentiation in
      the S/G ratio of lignin in particular was positively correlated with latitude
      (R(2) = 76%), which may be driven by either adaptation to climate or associated
      biotic factors.

PMID- 22384328
TI  - polo Is Identified as a Suppressor of bubR1 Nondisjunction in a Deficiency Screen
      of the Third Chromosome in Drosophila melanogaster.
AB  - We have previously characterized an EMS-induced allele of the bubR1 gene
      (bubR1(D1326N)) that separates the two functions of BubR1, causing meiotic
      nondisjunction but retaining spindle assembly checkpoint activity during somatic
      cell division in Drosophila melanogaster. Using this allele, we demonstrate that
      bubR1 meiotic nondisjunction is dosage sensitive, occurs for both exchange and
      nonexchange homologous chromosomes, and is associated with decreased maintenance
      of sister chromatid cohesion and of the synaptonemal complex during prophase I
      progression. We took advantage of these features to perform a genetic screen
      designed to identify third chromosome deficiencies having a dominant effect on
      bubR1(D1326N)/bubR1(rev1) meiotic phenotypes. We tested 65 deficiencies covering
      60% of the third chromosome euchromatin. Among them, we characterized 24
      deficiencies having a dominant effect on bubR1(D1326N)/bubR1(rev1) meiotic
      phenotypes that we classified in two groups: (1) suppressor of nondisjunction and
      (2) enhancer of nondisjunction. Among these 24 deficiencies, our results show
      that deficiencies uncovering the polo locus act as suppressor of bubR1
      nondisjunction by delaying meiotic prophase I progression and restoring chiasmata
      formation as observed by the loading of the condensin subunit SMC2. Furthermore,
      we identified two deficiencies inducing a lethal phenotype during embryonic
      development and thus affecting BubR1 kinase activity in somatic cells and one
      deficiency causing female sterility. Overall, our genetic screening strategy
      proved to be highly sensitive for the identification of modifiers of BubR1 kinase
      activity in both meiosis and mitosis.

PMID- 22384329
TI  - Stacks: building and genotyping Loci de novo from short-read sequences.
AB  - Advances in sequencing technology provide special opportunities for genotyping
      individuals with speed and thrift, but the lack of software to automate the
      calling of tens of thousands of genotypes over hundreds of individuals has
      hindered progress. Stacks is a software system that uses short-read sequence data
      to identify and genotype loci in a set of individuals either de novo or by
      comparison to a reference genome. From reduced representation Illumina sequence
      data, such as RAD-tags, Stacks can recover thousands of single nucleotide
      polymorphism (SNP) markers useful for the genetic analysis of crosses or
      populations. Stacks can generate markers for ultra-dense genetic linkage maps,
      facilitate the examination of population phylogeography, and help in reference
      genome assembly. We report here the algorithms implemented in Stacks and
      demonstrate their efficacy by constructing loci from simulated RAD-tags taken
      from the stickleback reference genome and by recapitulating and improving a
      genetic map of the zebrafish, Danio rerio.

PMID- 22384330
TI  - High-Resolution Genotyping of Wild Barley Introgression Lines and Fine-Mapping of
      the Threshability Locus thresh-1 Using the Illumina GoldenGate Assay.
AB  - Genetically well-characterized mapping populations are a key tool for rapid and
      precise localization of quantitative trait loci (QTL) and subsequent
      identification of the underlying genes. In this study, a set of 73 introgression
      lines (S42ILs) originating from a cross between the spring barley cultivar
      Scarlett (Hordeum vulgare ssp. vulgare) and the wild barley accession ISR42-8 (H.
      v. ssp. spontaneum) was subjected to high-resolution genotyping with an Illumina
      1536-SNP array. The array enabled a precise localization of the wild barley
      introgressions in the elite barley background. Based on 636 informative SNPs, the
      S42IL set represents 87.3% of the wild barley genome, where each line contains on
      average 3.3% of the donor genome. Furthermore, segregating high-resolution
      mapping populations (S42IL-HRs) were developed for 70 S42ILs in order to
      facilitate QTL fine-mapping and cloning. As a case study, we used the developed
      genetic resources to rapidly identify and fine-map the novel locus thresh-1 on
      chromosome 1H that controls grain threshability. Here, the recessive wild barley
      allele confers a difficult to thresh phenotype, suggesting that thresh-1 played
      an important role during barley domestication. Using a S42IL-HR population,
      thresh-1 was fine-mapped within a 4.3cM interval that was predicted to contain
      candidate genes involved in regulation of plant cell wall composition. The set of
      wild barley introgression lines and derived high-resolution populations are ideal
      tools to speed up the process of mapping and further dissecting QTL, which
      ultimately clears the way for isolating the genes behind QTL effects.

PMID- 22384331
TI  - Genome-wide analysis to identify pathways affecting telomere-initiated senescence
      in budding yeast.
AB  - In telomerase-deficient yeast cells, like equivalent mammalian cells, telomeres
      shorten over many generations until a period of senescence/crisis is reached.
      After this, a small fraction of cells can escape senescence, principally using
      recombination-dependent mechanisms. To investigate the pathways that affect entry
      into and recovery from telomere-driven senescence, we combined a gene deletion
      disrupting telomerase (est1Delta) with the systematic yeast deletion collection
      and measured senescence characteristics in high-throughput assays. As expected,
      the vast majority of gene deletions showed no strong effects on entry into/exit
      from senescence. However, around 200 gene deletions behaving similarly to a
      rad52Deltaest1Delta archetype (rad52Delta affects homologous recombination)
      accelerated entry into senescence, and such cells often could not recover growth.
      A smaller number of strains similar to a rif1Deltaest1Delta archetype (rif1Delta
      affects proteins that bind telomeres) accelerated entry into senescence but also
      accelerated recovery from senescence. Our genome-wide analysis identifies genes
      that affect entry into and/or exit from telomere-initiated senescence and will be
      of interest to those studying telomere biology, replicative senescence, cancer,
      and ageing. Our dataset is complementary to other high-throughput studies
      relevant to telomere biology, genetic stability, and DNA damage responses.

PMID- 22384332
TI  - Mixed model association mapping for fusarium head blight resistance in tunisian
      derived durum wheat populations.
AB  - Sources of resistance to Fusarium head blight (FHB) in wheat are mostly
      restricted to Chinese hexaploid genotypes. The effort to incorporate the
      resistance from hexaploid wheat or wild relatives to cultivated durum wheat
      (Triticum turgidum L. var. durum Desf.) have not been successful in providing
      resistance to the level of the donor parents. In this study, we used 171
      BC(1)F(6) and 169 BC(1)F(7) lines derived from crossing of four Tunisian
      tetraploid sources of resistance (Tun7, Tun18, Tun34, Tun36) with durum cultivars
      'Ben,' 'Maier,' 'Lebsock,' and 'Mountrail' for association studies. The Tun18 and
      Tun7 FHB resistances were found to be comparable to the best hexaploid wheat
      sources. A new significant QTL for FHB resistance was identified on the long arm
      of chromosome 5B (Qfhs.ndsu-5BL) with both association and classical QTL mapping
      analysis. Linkage disequilibrium (LD) blocks extending up to 40 cM were evident
      in these populations. The linear mixed model considering the structure (Q or P)
      and the kinship matrix (K(T)) estimated by restricted maximum likelihood (REML)
      was identified as the best for association studies in a mixture of wheat
      populations from a breeding program. The results of association mapping analysis
      also demonstrated a region on the short arm of chromosome 3B as potentially
      linked to FHB resistance. This region is in proximity of major FHB resistance
      gene fhb1 reported in hexaploid wheat. A possibility of having susceptibility or
      suppressor of resistance gene(s) on durum wheat chromosome 2A was further
      confirmed in this material, explaining the problem in developing resistant
      genotypes without counter selection against this region.

PMID- 22384333
TI  - A global perspective of the genetic basis for carbonyl stress resistance.
AB  - The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark
      of cellular aging and other diseases, yet the detailed cellular effects of this
      universal phenomena are poorly understood. An understanding of the global effects
      of CS will provide insight into disease mechanisms and can guide the development
      of therapeutics and lifestyle changes to ameliorate their effects. To identify
      cellular functions important for the response to carbonyl stress, multiple genome
      wide genetic screens were performed using two known inducers of CS. We found that
      different cellular functions were required for resistance to stress induced by
      methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance
      of macromolecule catabolism processes for resistance to MG, confirming and
      extending known mechanisms of MG toxicity, including modification of DNA, RNA,
      and proteins. Combining our results with related studies that examined the
      effects of ROS allowed a comprehensive view of the diverse range of cellular
      functions affected by both oxidative and carbonyl stress. To understand how these
      diverse cellular functions interact, we performed a quantitative epistasis
      analysis by creating multimutant strains from those individual genes required for
      glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent
      genetic interactions. In summary, using multiple genome-wide approaches provides
      an effective approach to dissect the poorly understood effects of glyoxal in
      vivo. These data, observations, and comprehensive dataset provide 1) a
      comprehensive view of carbonyl stress, 2) a resource for future studies in other
      cell types, and 3) a demonstration of how inexpensive cell-based assays can
      identify complex gene-environment toxicities.

PMID- 22384334
TI  - Integrating Rare-Variant Testing, Function Prediction, and Gene Network in
      Composite Resequencing-Based Genome-Wide Association Studies (CR-GWAS).
AB  - High-density array-based genome-wide association studies (GWAS) are complemented
      by exome sequencing and whole-genome resequencing-based association studies. Here
      we present a composite resequencing-based genome-wide association study (CR-GWAS)
      strategy that systematically exploits collective biological information and
      analytical tools for a robust analysis. We showcased the utility of this strategy
      by using Arabidopsis (Arabidopsis thaliana) resequencing data. Bioinformatic
      predictions of biological function alteration at each locus were integrated into
      the process of association testing of both common and rare variants for complex
      traits with a suite of statistics. Significant signals were then filtered with a
      priori candidate loci generated from genome database and gene network models to
      obtain a posteriori candidate loci. A probabilistic gene network (AraNet) that
      interrogates network neighborhoods of genes was then used to expand the filtering
      power to examine the significant testing signals. Using this strategy, we
      confirmed the known true positives and identified several new promising
      associations. Promising genes (AP1, FCA, FRI, FLC, FLM, SPL5, FY, and DCL2) were
      shown to control for flowering time through either common variants or rare
      variants within a diverse set of Arabidopsis accessions. Although many of these
      candidate genes were cloned earlier with mutational studies, identifying their
      allele variation contribution to overall phenotypic variation among diverse
      natural accessions is critical. Our rare allele testing established a greater
      number of connections than previous analyses in which this issue was not
      addressed. More importantly, our results demonstrated the potential of
      integrating various biological, statistical, and bioinformatic tools into complex
      trait dissection.

PMID- 22384335
TI  - G3, GENETICS, and the GSA: Two Journals, One Mission.

PMID- 22384337
TI  - Variable transposition of eight maize activator (ac) elements located on the
      short arm of chromosome 1.
AB  - Eight Activator (Ac) transposable elements mapped to the maize chromosome arm 1S
      were assessed for Ac transposition rates. For each of the Ac stocks, plants
      homozygous for the single Ac element and the Ds reporter r1-sc:m3 on chromosome
      10 were crossed as females by a homozygous r1-sc:m3 tester color-converted W22
      line. The resulting ears produced mostly coarsely spotted kernels and a low
      frequency of either near-colorless fine-spotted kernels or nonspotted kernels.
      The relative frequency of these two types of near-colorless kernels differed
      among the eight Ac stocks. The extent to which increased Ac dosage results in
      nonspotted kernels may be Ac-specific. Although all of the Ac elements are in
      near-isogenic inbred W22 lines, they varied to a large extent in their
      transposition frequency. These differences might possibly result from structural
      differences among the Ac elements. Because one pair of Ac elements derived from
      Ac33 on chromosome arm 5S differed about 13-fold in transposition frequency and a
      second pair of Ac elements derived from Ac12 on chromosome arm 1S differed about
      3-fold in transposition frequency, this is not a likely explanation for all eight
      Ac elements. The data presented here support the notion that the differences in
      transposition frequency of the eight Ac elements may be a reflection of
      variability in Ac transcription or accessibility of the transposase to the Ac
      element, resulting from differences in the chromatin environments wherein the Ac
      elements are located. This is the first report of variability in transposition
      rates among different Ac donor lines.

PMID- 22384336
TI  - Chemical and Synthetic Genetic Array Analysis Identifies Genes that Suppress
      Xylose Utilization and Fermentation in Saccharomyces cerevisiae.
AB  - Though highly efficient at fermenting hexose sugars, Saccharomyces cerevisiae has
      limited ability to ferment five-carbon sugars. As a significant portion of sugars
      found in cellulosic biomass is the five-carbon sugar xylose, S. cerevisiae must
      be engineered to metabolize pentose sugars, commonly by the addition of exogenous
      genes from xylose fermenting fungi. However, these recombinant strains grow
      poorly on xylose and require further improvement through rational engineering or
      evolutionary adaptation. To identify unknown genes that contribute to improved
      xylose fermentation in these recombinant S. cerevisiae, we performed genome-wide
      synthetic interaction screens to identify deletion mutants that impact xylose
      utilization of strains expressing the xylose isomerase gene XYLA from Piromyces
      sp. E2 alone or with an additional copy of the endogenous xylulokinase gene XKS1.
      We also screened the deletion mutant array to identify mutants whose growth is
      affected by xylose. Our genetic network reveals that more than 80 nonessential
      genes from a diverse range of cellular processes impact xylose utilization.
      Surprisingly, we identified four genes, ALP1, ISC1, RPL20B, and BUD21, that when
      individually deleted improved xylose utilization of both S. cerevisiae S288C and
      CEN.PK strains. We further characterized BUD21 deletion mutant cells in batch
      fermentations and found that they produce ethanol even the absence of exogenous
      XYLA. We have demonstrated that the ability of laboratory strains of S.
      cerevisiae to utilize xylose as a sole carbon source is suppressed, which implies
      that S. cerevisiae may not require the addition of exogenous genes for efficient
      xylose fermentation.

PMID- 22384338
TI  - Deciphering the molecular basis of wine yeast fermentation traits using a
      combined genetic and genomic approach.
AB  - The genetic basis of the phenotypic diversity of yeast is still poorly
      understood. Wine yeast strains have specific abilities to grow and ferment under
      stressful conditions compared with other strains, but the genetic basis
      underlying these traits is unknown. Understanding how sequence variation
      influences such phenotypes is a major challenge to address adaptation mechanisms
      of wine yeast. We aimed to identify the genetic basis of fermentation traits and
      gain insight into their relationships with variations in gene expression among
      yeast strains. We combined fermentation trait QTL mapping and expression
      profiling of fermenting cells in a segregating population from a cross between a
      wine yeast derivative and a laboratory strain. We report the identification of
      QTL for various fermentation traits (fermentation rates, nitrogen utilization,
      metabolites production) as well as expression QTL (eQTL). We found that many
      transcripts mapped to several eQTL hotspots and that two of them overlapped with
      QTL for fermentation traits. A QTL controlling the maximal fermentation rate and
      nitrogen utilization overlapping with an eQTL hotspot was dissected. We
      functionally demonstrated that an allele of the ABZ1 gene, localized in the
      hotspot and involved in p-aminobenzoate biosynthesis, controls the fermentation
      rate through modulation of nitrogen utilization. Our data suggest that the
      laboratory strain harbors a defective ABZ1 allele, which triggers strong
      metabolic and physiological alterations responsible for the generation of the
      eQTL hotspot. They also suggest that a number of gene expression differences
      result from some alleles that trigger major physiological disturbances.

PMID- 22384339
TI  - Identification and Precise Mapping of Resistant QTLs of Cercospora Leaf Spot
      Resistance in Sugar Beet (Beta vulgaris L.).
AB  - The complex inheritance of resistance to Cercospora leaf spot (CLS), the most
      severe fungal foliar disease in sugar beet, was investigated by means of
      quantitative trait loci (QTL) analysis. Over a three year period, recombinant
      inbred lines (RILs) of sugar beet (Beta vulgaris L.), generated through a cross
      between lines resistant ('NK-310mm-O') and susceptible ('NK-184mm-O') to CLS,
      were field-tested for their resistance to the pathogen. Composite interval
      mapping (CIM) showed four QTL involved in CLS resistance to be consistently
      detected. Two resistant QTL (qcr1 on chromosome III, qcr4 on chromosome IX)
      bearing 'NK-310mm-O' derived alleles promoted resistance. Across 11
      investigations, the qcr1 and qcr4 QTL explained approximately 10% and over 20%,
      respectively, of the variance in the resistance index. Two further QTL (qcr2 on
      chromosome IV, qcr3 on chromosome VI) bearing 'NK-184mm-O' derived alleles each
      explained about 10% of the variance. To identify the monogenic effect of the
      resistance, two QTL derived from 'NK-310mm-O' against the genetic background of
      'NK-184mm-O', using molecular markers. The qcr1 and qcr4 were precisely mapped as
      single QTL, using progenies BC(5)F(1) and BC(2)F(1), respectively. The qcr1 that
      was located near e11m36-8 had CLS disease severity indices (DSI) about 15% lower
      than plants homozygous for the 'NK-184mm-O' genotype. As with qcr1, heterozygosis
      of the qcr4 that was located near e17m47-81 reduced DSI by about 45% compared to
      homozygosis. These two resistant QTL might be of particular value in marker
      assisted selection (MAS) programs in CLS resistance progression.

PMID- 22384340
TI  - Identification of an active new mutator transposable element in maize.
AB  - Robertson's Mutator (Mu) system has been used in large scale mutagenesis in
      maize, exploiting its high mutation frequency, controllability, preferential
      insertion in genes, and independence of donor location. Eight Mutator elements
      have been fully characterized (Mu1, Mu2 /Mu1.7, Mu3, Mu4, Mu5, Mu6/7, Mu8, MuDR),
      and three are defined by TIR (Mu10, Mu11 and Mu12). The genome sequencing
      revealed a complex family of Mu-like-elements (MULEs) in the B73 genome. In this
      article, we report the identification of a new Mu element, named Mu13. Mu13
      showed typical Mu characteristics by having a ~220 bp TIR, creating a 9 bp target
      site duplication upon insertion, yet the internal sequence is completely
      different from previously identified Mu elements. Mu13 is not present in the B73
      genome or a Zea mays subsp. parviglumis accession, but in W22 and several inbreds
      that found the Robertson's Mutator line. Analysis of mutants isolated from the
      UniformMu mutagenic population indicated that the Mu13 element is active in
      transposition. Two novel insertions were found in expressed genes. To test other
      unknown Mu elements, we selected six new Mu elements from the B73 genome.
      Southern analysis indicated that most of these elements were present in the
      UniformMu lines. From these results, we conclude that Mu13 is a new and active Mu
      element that significantly contributed to the mutagenesis in the UniformMu
      population. The Robertson's Mutator line may harbor other unknown active Mu
      elements.

PMID- 22384341
TI  - Rediscovery by Whole Genome Sequencing: Classical Mutations and Genome
      Polymorphisms in Neurospora crassa.
AB  - Classical forward genetics has been foundational to modern biology, and has been
      the paradigm for characterizing the role of genes in shaping phenotypes for
      decades. In recent years, reverse genetics has been used to identify the
      functions of genes, via the intentional introduction of variation and subsequent
      evaluation in physiological, molecular, and even population contexts. These
      approaches are complementary and whole genome analysis serves as a bridge between
      the two. We report in this article the whole genome sequencing of eighteen
      classical mutant strains of Neurospora crassa and the putative identification of
      the mutations associated with corresponding mutant phenotypes. Although some
      strains carry multiple unique nonsynonymous, nonsense, or frameshift mutations,
      the combined power of limiting the scope of the search based on genetic markers
      and of using a comparative analysis among the eighteen genomes provides strong
      support for the association between mutation and phenotype. For ten of the
      mutants, the mutant phenotype is recapitulated in classical or gene deletion
      mutants in Neurospora or other filamentous fungi. From thirteen to 137 nonsense
      mutations are present in each strain and indel sizes are shown to be highly
      skewed in gene coding sequence. Significant additional genetic variation was
      found in the eighteen mutant strains, and this variability defines multiple
      alleles of many genes. These alleles may be useful in further genetic and
      molecular analysis of known and yet-to-be-discovered functions and they invite
      new interpretations of molecular and genetic interactions in classical mutant
      strains.

PMID- 22384342
TI  - A synthetic human kinase can control cell cycle progression in budding yeast.
AB  - The DDK kinase complex, composed of Cdc7 and Dbf4, is required for S-phase
      progression. The two component proteins show different degrees of sequence
      conservation between human and yeast. Here, we determine that Saccharomyces
      cerevisiae bearing human CDC7 and DBF4 grows comparably to cells with yeast DDK
      under standard growth conditions. HsDrf1 (a second human Dbf4-like protein) does
      not support growth, suggesting that HsDbf4 is the true ortholog of ScDbf4. Both
      human subunits are required to complement yeast cdc7Delta or dbf4Delta due to the
      inability of human Cdc7 or Dbf4 to interact with the corresponding yeast protein.
      Flow cytometry indicates normal cell cycle progression for yeast containing human
      DDK. However, yeast containing human DDK is sensitive to long-term exposure to
      hydroxyurea and fails to sporulate, suggesting that human DDK substitutes for
      some, but not all, of yeast DDK's functions. We mapped the region of Cdc7
      required for species-specific function of DDK to the C-terminus of Cdc7 by
      substituting the yeast C-terminal 55 amino acid residues in place of the
      equivalent human residues. The resulting hybrid protein supported growth of a
      cdc7Delta strain only in the presence of ScDBF4. The strain supported by the
      hybrid CDC7 was not sensitive to HU and formed tetrads. Together, our data
      indicate that DDK's targeting of its essential substrate is conserved between
      species, whereas the interactions within DDK are species specific.

PMID- 22384343
TI  - Replication stress-induced chromosome breakage is correlated with replication
      fork progression and is preceded by single-stranded DNA formation.
AB  - Chromosome breakage as a result of replication stress has been hypothesized to be
      the direct consequence of defective replication fork progression, or "collapsed"
      replication forks. However, direct and genome-wide evidence that collapsed
      replication forks give rise to chromosome breakage is still lacking. Previously
      we showed that a yeast replication checkpoint mutant mec1-1, after transient
      exposure to replication impediment imposed by hydroxyurea (HU), failed to
      complete DNA replication, accumulated single-stranded DNA (ssDNA) at the
      replication forks, and fragmented its chromosomes. In this study, by following
      replication fork progression genome-wide via ssDNA detection and by direct
      mapping of chromosome breakage after HU exposure, we have tested the hypothesis
      that the chromosome breakage in mec1 cells occurs at collapsed replication forks.
      We demonstrate that sites of chromosome breakage indeed correlate with
      replication fork locations. Moreover, ssDNA can be detected prior to chromosome
      breakage, suggesting that ssDNA accumulation is the common precursor to double
      strand breaks at collapsed replication forks.

PMID- 22384344
TI  - QTL Controlling Masculinization of Ear Tips in a Maize (Zea mays L.)
      Intraspecific Cross.
AB  - Maize is unique among cereal grasses because of its monoecious flowering habit.
      Male flowers are normally restricted to the tassel that terminates the primary
      shoot, whereas female flowers occur as ears at the terminal nodes of lateral
      branches. We observed Ki14, a tropical maize inbred that produces an ear tipped
      by a staminate (male) spike under certain environmental conditions, such as long
      daylengths. Recombinant inbred lines derived from the cross between temperate
      line B97, which was never observed to produce a staminate ear tip, and Ki14
      segregated for the trait under long daylengths. Some progeny lines that had even
      longer staminate tips than Ki14 were male fertile. We mapped three QTL
      controlling staminate ear tip using a two-part (binomial plus normal) model. A
      major QTL on chromosome 3 had a large effect on penetrance of the trait (whether
      a line would produce staminate ear tips or not) as well as its severity (the
      length of the staminate tip). This QTL seems to be linked to, but at a distinct
      position from, a previously mapped QTL controlling the proportion of staminate
      florets in ears in progeny from crosses between maize and teosinte. Two
      additional QTL affecting staminate ear tip severity overlapped with QTL
      controlling photoperiod response previously mapped in this population. Alleles
      conferring photoperiod sensitivity for delayed flowering at these QTL seem to
      enhance the production of staminate ear tips under long daylengths.

PMID- 22384345
TI  - Multiple Quantitative Trait Loci Influence the Shape of a Male-Specific Genital
      Structure in Drosophila melanogaster.
AB  - The observation that male genitalia diverge more rapidly than other morphological
      traits during evolution is taxonomically widespread and likely due to some form
      of sexual selection. One way to elucidate the evolutionary forces acting on these
      traits is to detail the genetic architecture of variation both within and between
      species, a program of research that is considerably more tractable in a model
      system. Drosophila melanogaster and its sibling species, D. simulans, D.
      mauritiana, and D. sechellia, are morphologically distinguishable only by the
      shape of the posterior lobe, a male-specific elaboration of the genital arch. We
      extend earlier studies identifying quantitative trait loci (QTL) responsible for
      lobe divergence across species and report the first genetic dissection of lobe
      shape variation within a species. Using an advanced intercross mapping design, we
      identify three autosomal QTL contributing to the difference in lobe shape between
      a pair of D. melanogaster inbred lines. The QTL each contribute 4.6-10.7% to
      shape variation, and two show a significant epistatic interaction. Interestingly,
      these intraspecific QTL map to the same locations as interspecific lobe QTL,
      implying some shared genetic control of the trait within and between species. As
      a first step toward a mechanistic understanding of natural lobe shape variation,
      we find an association between our QTL data and a set of genes that show sex
      biased expression in the developing genital imaginal disc (the precursor of the
      adult genitalia). These genes are good candidates to harbor naturally segregating
      polymorphisms contributing to posterior lobe shape.

PMID- 22384347
TI  - SAD-3, a Putative Helicase Required for Meiotic Silencing by Unpaired DNA,
      Interacts with Other Components of the Silencing Machinery.
AB  - In Neurospora crassa, genes lacking a pairing partner during meiosis are
      suppressed by a process known as meiotic silencing by unpaired DNA (MSUD). To
      identify novel MSUD components, we have developed a high-throughput reverse
      genetic screen for use with the N. crassa knockout library. Here we describe the
      screening method and the characterization of a gene (sad-3) subsequently
      discovered. SAD-3 is a putative helicase required for MSUD and sexual spore
      production. It exists in a complex with other known MSUD proteins in the
      perinuclear region, a center for meiotic silencing activity. Orthologs of SAD-3
      include Schizosaccharomyces pombe Hrr1, a helicase required for RNAi-induced
      heterochromatin formation. Both SAD-3 and Hrr1 interact with an RNA-directed RNA
      polymerase and an Argonaute, suggesting that certain aspects of silencing complex
      formation may be conserved between the two fungal species.

PMID- 22384346
TI  - Genome-wide Fitness Profiles Reveal a Requirement for Autophagy During Yeast
      Fermentation.
AB  - The ability of cells to respond to environmental changes and adapt their
      metabolism enables cell survival under stressful conditions. The budding yeast
      Saccharomyces cerevisiae (S. cerevisiae) is particularly well adapted to the
      harsh conditions of anaerobic wine fermentation. However, S. cerevisiae gene
      function has not been previously systematically interrogated under conditions of
      industrial fermentation. We performed a genome-wide study of essential and
      nonessential S. cerevisiae gene requirements during grape juice fermentation to
      identify deletion strains that are either depleted or enriched within the viable
      fermentative population. Genes that function in autophagy and ubiquitin
      proteasome degradation are required for optimal survival during fermentation,
      whereas genes that function in ribosome assembly and peroxisome biogenesis impair
      fitness during fermentation. We also uncover fermentation phenotypes for 139
      uncharacterized genes with no previously known cellular function. We demonstrate
      that autophagy is induced early in wine fermentation in a nitrogen-replete
      environment, suggesting that autophagy may be triggered by other forms of stress
      that arise during fermentation. These results provide insights into the complex
      fermentation process and suggest possible means for improvement of industrial
      fermentation strains.

PMID- 22384348
TI  - Generation of highly homogeneous strains of zebrafish through full sib-pair
      mating.
AB  - Genetically homogeneous populations, such as inbred strains, are powerful
      experimental tools that are ideally suited for studying immunology, cancer, and
      genetics of complex traits. The zebrafish, Danio rerio, has been underutilized in
      these research areas because homogeneous strains of experimental fish have not
      been available in tractable condition. Here, we attempted to inbreed two
      zebrafish wild-type strains, Tubingen and India, through full sib-pair mating.
      Although the inbred Tubingen strain failed to thrive and was lost after 13
      generations, an inbred India strain (IM) has been maintained successfully. The IM
      strain has endured 16 generations of inbreeding and has maintained a healthy
      condition. Two additional strains, IM12m and IM14m, were established as closed
      colonies from the branches of the IM strain. Genotype analyses using genetic
      markers revealed a dramatic decrease in polymorphisms (62% dropped to 5%) in both
      IM (generation 14) and the two closed colonies. This indicates a high level of
      homogeneity in these strains. Furthermore, scale transplantations between
      individuals within each strain were successful. These data suggest that extremely
      homogeneous zebrafish strains have been established, thereby creating a valuable
      resource for practical application.

PMID- 22384349
TI  - Polymorphism and Divergence in Two Willow Species, Salix viminalis L. and Salix
      schwerinii E. Wolf.
AB  - We investigated species divergence, present and past gene flow, levels of
      nucleotide polymorphism, and linkage disequilibrium in two willows from the plant
      genus Salix. Salix belongs together with Populus to the Salicaceae family;
      however, most population genetic studies of Salicaceae have been performed in
      Populus, the model genus in forest biology. Here we present a study on two
      closely related willow species Salix viminalis and S. schwerinii, in which we
      have resequenced 33 and 32 nuclear gene segments representing parts of 18 nuclear
      loci in 24 individuals for each species. We used coalescent simulations and
      estimated the split time to around 600,000 years ago and found that there is
      currently limited gene flow between the species. Mean intronic nucleotide
      diversity across gene segments was slightly higher in S. schwerinii (pi(i) =
      0.00849) than in S. viminalis (pi(i) = 0.00655). Compared with other angiosperm
      trees, the two willows harbor intermediate levels of silent polymorphisms. The
      decay of linkage disequilibrium was slower in S. viminalis compared with S.
      schwerinii, and we speculate that this is due to different demographic histories
      as S. viminalis has been partly domesticated in Europe.

PMID- 22384351
TI  - Amino Acid Substitutions in the Caenorhabditis elegans RNA Polymerase II Large
      Subunit AMA-1/RPB-1 that Result in alpha-Amanitin Resistance and/or Reduced
      Function.
AB  - Mutations in the Caenorhabditis elegans RNA polymerase II AMA-1/RPB-1 subunit
      that cause alpha-amanitin resistance and/or developmental defects were isolated
      previously. We identified 12 of these mutations and mapped them onto the
      Saccharomyces cerevisiae RPB1 structure to provide insight into AMA-1 regions
      that are essential for development in a multicellular organism.

PMID- 22384350
TI  - Sequence Analysis of the Segmental Duplication Responsible for Paris Sex-Ratio
      Drive in Drosophila simulans.
AB  - Sex-ratio distorters are X-linked selfish genetic elements that facilitate their
      own transmission by subverting Mendelian segregation at the expense of the Y
      chromosome. Naturally occurring cases of sex-linked distorters have been reported
      in a variety of organisms, including several species of Drosophila; they trigger
      genetic conflict over the sex ratio, which is an important evolutionary force.
      However, with a few exceptions, the causal loci are unknown. Here, we molecularly
      characterize the segmental duplication involved in the Paris sex-ratio system
      that is still evolving in natural populations of Drosophila simulans. This 37.5
      kb tandem duplication spans six genes, from the second intron of the Trf2 gene
      (TATA box binding protein-related factor 2) to the first intron of the org-1 gene
      (optomotor-blind-related-gene-1). Sequence analysis showed that the duplication
      arose through the production of an exact copy on the template chromosome itself.
      We estimated this event to be less than 500 years old. We also detected specific
      signatures of the duplication mechanism; these support the Duplication-Dependent
      Strand Annealing model. The region at the junction between the two duplicated
      segments contains several copies of an active transposable element, Hosim1,
      alternating with 687 bp repeats that are noncoding but transcribed. The almost
      complete sequence identity between copies made it impossible to complete the
      sequencing and assembly of this region. These results form the basis for the
      functional dissection of Paris sex-ratio drive and will be valuable for future
      studies designed to better understand the dynamics and the evolutionary
      significance of sex chromosome drive.

PMID- 22384352
TI  - Double-Strand Break Repair and Holliday Junction Processing Are Required for
      Chromosome Processing in Stationary-Phase Escherichia coli Cells.
AB  - As nutrients are depleted and cell division ceases in batch cultures of bacteria,
      active processes are required to ensure that each cell has a complete copy of its
      genome. How chromosome number is manipulated and maintained in nondividing
      bacterial cells is not fully understood. Using flow cytometric analysis of cells
      from different growth phases, we show that the Holliday junction-processing
      enzymes RuvABC and RecG, as well as RecBCD, the enzyme complex that initiates DNA
      double-strand break repair, are required to establish the normal distribution of
      fluorescent peaks, which is commonly accepted to reflect the distribution of
      chromosome numbers. Our results reveal that these proteins are required for the
      proper processing of chromosomes in stationary phase.

PMID- 22384353
TI  - Partitioning transcript variation in Drosophila: abundance, isoforms, and
      alleles.
AB  - Multilevel analysis of transcription is facilitated by a new array design that
      includes modules for assessment of differential expression, isoform usage, and
      allelic imbalance in Drosophila. The ~2.5 million feature chip incorporates a
      large number of controls, and it contains 18,769 3' expression probe sets and
      61,919 exon probe sets with probe sequences from Drosophila melanogaster and
      60,118 SNP probe sets focused on Drosophila simulans. An experiment in D.
      simulans identified genes differentially expressed between males and females (34%
      in the 3' expression module; 32% in the exon module). These proportions are
      consistent with previous reports, and there was good agreement (kappa = 0.63)
      between the modules. Alternative isoform usage between the sexes was identified
      for 164 genes. The SNP module was verified with resequencing data. Concordance
      between resequencing and the chip design was greater than 99%. The design also
      proved apt in separating alleles based upon hybridization intensity. Concordance
      between the highest hybridization signals and the expected alleles in the
      genotype was greater than 96%. Intriguingly, allelic imbalance was detected for
      37% of 6579 probe sets examined that contained heterozygous SNP loci. The large
      number of probes and multiple probe sets per gene in the 3' expression and exon
      modules allows the array to be used in D. melanogaster and in closely related
      species. The SNP module can be used for allele specific expression and genotyping
      of D. simulans.

PMID- 22384354
TI  - QTL Mapping and Candidate Gene Analysis of Telomere Length Control Factors in
      Maize (Zea mays L.).
AB  - Telomere length is a quantitative trait important for many cellular functions.
      Failure to regulate telomere length contributes to genomic instability, cellular
      senescence, cancer, and apoptosis in humans, but the functional significance of
      telomere regulation in plants is much less well understood. To gain a better
      understanding of telomere biology in plants, we used quantitative trait locus
      (QTL) mapping to identify genetic elements that control telomere length variation
      in maize (Zea mays L.). For this purpose, we measured the median and mean
      telomere lengths from 178 recombinant inbred lines of the IBM mapping population
      and found multiple regions that collectively accounted for 33-38% of the
      variation in telomere length. Two-way analysis of variance revealed interaction
      between the quantitative trait loci at genetic bin positions 2.09 and 5.04.
      Candidate genes within these and other significant QTL intervals, along with
      select genes known a priori to regulate telomere length, were tested for
      correlations between expression levels and telomere length in the IBM population
      and diverse inbred lines by quantitative real-time PCR. A slight but significant
      positive correlation between expression levels and telomere length was observed
      for many of the candidate genes, but Ibp2 was a notable exception, showing
      instead a negative correlation. A rad51-like protein (TEL-MD_5.04) was strongly
      supported as a candidate gene by several lines of evidence. Our results highlight
      the value of QTL mapping plus candidate gene expression analysis in a genetically
      diverse model system for telomere research.

PMID- 22384355
TI  - The SPRED1 Variants Repository for Legius Syndrome.
AB  - Legius syndrome (LS) is an autosomal dominant disorder caused by germline loss-of
      function mutations in the sprouty-related, EVH1 domain containing 1 (SPRED1)
      gene. The phenotype of LS is multiple cafe au lait macules (CALM) with other
      commonly reported manifestations, including intertriginous freckling, lipomas,
      macrocephaly, and learning disabilities including ADHD and developmental delays.
      Since the earliest signs of LS and neurofibromatosis type 1 (NF1) syndrome are
      pigmentary findings, the two are indistinguishable and individuals with LS may
      meet the National Institutes of Health diagnostic criteria for NF1 syndrome.
      However, individuals are not known to have an increased risk for developing
      tumors (compared with NF1 patients). It is therefore important to fully
      characterize the phenotype differences between NF1 and LS because the prognoses
      of these two disorders differ greatly. We have developed a mutation database that
      characterizes the known variants in the SPRED1 gene in an effort to facilitate
      this process for testing and interpreting results. This database is free to the
      public and will be updated quarterly.

PMID- 22384356
TI  - Genotype imputation with thousands of genomes.
AB  - Genotype imputation is a statistical technique that is often used to increase the
      power and resolution of genetic association studies. Imputation methods work by
      using haplotype patterns in a reference panel to predict unobserved genotypes in
      a study dataset, and a number of approaches have been proposed for choosing
      subsets of reference haplotypes that will maximize accuracy in a given study
      population. These panel selection strategies become harder to apply and interpret
      as sequencing efforts like the 1000 Genomes Project produce larger and more
      diverse reference sets, which led us to develop an alternative framework. Our
      approach is built around a new approximation that uses local sequence similarity
      to choose a custom reference panel for each study haplotype in each region of the
      genome. This approximation makes it computationally efficient to use all
      available reference haplotypes, which allows us to bypass the panel selection
      step and to improve accuracy at low-frequency variants by capturing unexpected
      allele sharing among populations. Using data from HapMap 3, we show that our
      framework produces accurate results in a wide range of human populations. We also
      use data from the Malaria Genetic Epidemiology Network (MalariaGEN) to provide
      recommendations for imputation-based studies in Africa. We demonstrate that our
      approximation improves efficiency in large, sequence-based reference panels, and
      we discuss general computational strategies for modern reference datasets. Genome
      wide association studies will soon be able to harness the power of thousands of
      reference genomes, and our work provides a practical way for investigators to use
      this rich information. New methodology from this study is implemented in the
      IMPUTE2 software package.

PMID- 22384357
TI  - Modulation of the activity of a polycomb-group response element in Drosophila by
      a mutation in the transcriptional activator woc.
AB  - Polycomb group response elements (PRE) are cis-regulatory elements that bind
      Polycomb group proteins. We are studying a 181-bp PRE from the
      Drosophilaengrailed gene. This PRE causes pairing-sensitive silencing of mini
      white in transgenes. Here we show that the 181-bp PRE also represses mini-white
      expression in flies with only one copy of the transgene. To isolate mutations
      that alter the activity of the 181-bp PRE, we screened for dominant suppressors
      of PRE-mediated mini-white repression. Dominant suppressors of mini-white
      repression were rare; we recovered only nine mutations out of 68,274 progeny
      screened. Two of the nine mutations isolated are due to the same single amino
      acid change in the transcriptional activator Woc (without children). Reversion
      experiments show that these are dominant gain-of-function mutations in woc. We
      suggest that Woc can interfere with the activity of the PRE. Our data have
      implications for how Polycomb group proteins act to either partially repress or
      completely silence their target genes.

PMID- 22384358
TI  - Detecting and Removing Ascertainment Bias in Microsatellites from the HGDP-CEPH
      Panel.
AB  - Although ascertainment bias in single nucleotide polymorphisms is a well-known
      problem, it is generally accepted that microsatellites have mutation rates too
      high for bias to be a concern. Here, we analyze in detail the large set of
      microsatellites typed for the Human Genetic Diversity Panel (HGDP)-CEPH panel. We
      develop a novel framework based on rarefaction to compare heterozygosity across
      markers with different mutation rates. We find that, whereas di- and tri
      nucleotides show similar patterns of within- and between-population
      heterozygosity, tetra-nucleotides are inconsistent with the other two motifs. In
      addition, di- and tri-nucleotides are consistent with 16 unbiased tetra
      nucleotide markers, whereas the HPGP-CEPH tetra-nucleotides are significantly
      different. This discrepancy is due to the HGDP-CEPH tetra-nucleotides being too
      homogeneous across Eurasia, even after their slower mutation rate is taken into
      account by rarefying the other markers. The most likely explanation for this
      pattern is ascertainment bias. We strongly advocate the exclusion of tetra
      nucleotides from future population genetics analysis of this dataset, and we
      argue that other microsatellite datasets should be investigated for the presence
      of bias using the approach outlined in this article.

PMID- 22384359
TI  - Miniature- and Multiple-Eyespot Loci in Chlamydomonas reinhardtii Define New
      Modulators of Eyespot Photoreception and Assembly.
AB  - The photosensory eyespot of the green alga Chlamydomonas reinhardtii is a model
      system for the study of organelle biogenesis and placement. Eyespot assembly and
      positioning are governed by several genetic loci that have been identified in
      forward genetic screens for phototaxis-defective mutants. These include the
      previously described miniature-eyespot mutant min1, the multiple-eyespot mutant
      mlt1, the eyeless mutants eye2 and eye3, and two previously uncharacterized
      eyespot mutants, min2 and mlt2. In this study, effects of miniature- and multiple
      eyespot mutations and their combinations on the localization and expression
      levels of the rhodopsin photoreceptor channelrhodopsin-1 (ChR1) and the
      localization of the eyespot-assembly proteins EYE2 and EYE3 were examined. min2
      mutants assemble a properly organized, albeit nonfunctional, eyespot that is
      slightly smaller than wild-type; however, combination of the min2 and mlt1
      mutations resulted in drastic reduction of photoreceptor levels. Both stationary
      phase mlt1 and mlt2 cells have supernumerary, mislocalized eyespots that exhibit
      partial or total dissociation of the eyespot layers. In these mutant strains,
      photoreceptor patches in the plasma membrane were never associated with pigment
      granule arrays in the chloroplast stroma unless EYE2 was present in the
      intervening envelope. The data suggest that MIN2 is required for the
      photoreceptive ability of the eyespot and that MLT2 plays a major role in
      regulating eyespot number, placement, and integrity.

PMID- 22384360
TI  - Genetic Background and Allorecognition Phenotype in Hydractinia
      symbiolongicarpus.
AB  - The Hydractinia allorecognition complex (ARC) was initially identified as a
      single chromosomal interval using inbred and congenic lines. The production of
      defined lines necessarily homogenizes genetic background and thus may be expected
      to obscure the effects of unlinked allorecognition loci should they exist. Here,
      we report the results of crosses in which inbred lines were out-crossed to wild
      type animals in an attempt to identify dominant, codominant, or incompletely
      dominant modifiers of allorecognition. A claim for the existence of modifiers
      unlinked to ARC was rejected for three different genetic backgrounds. Estimates
      of the genetic map distance of ARC in two wild-type haplotypes differed markedly
      from one another and from that measured in congenic lines. These results suggest
      that additional allodeterminants exist in the Hydractinia ARC.

PMID- 22384361
TI  - Genome-wide association analysis of ischemic stroke in young adults.
AB  - Ischemic stroke (IS) is among the leading causes of death in Western countries.
      There is a significant genetic component to IS susceptibility, especially among
      young adults. To date, research to identify genetic loci predisposing to stroke
      has met only with limited success. We performed a genome-wide association (GWA)
      analysis of early-onset IS to identify potential stroke susceptibility loci. The
      GWA analysis was conducted by genotyping 1 million SNPs in a biracial population
      of 889 IS cases and 927 controls, ages 15-49 years. Genotypes were imputed using
      the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic
      regression models adjusting for age, recruitment stages, and population structure
      were used to determine the association of IS with individual SNPs. Although no
      single SNP reached genome-wide significance (P < 5 * 10(-8)), we identified two
      SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 * 10(-7)) and rs1986743
      (in ARL6IP6; P = 2.7 * 10(-7)), strongly associated with early-onset stroke.
      These data suggest that a novel locus on human chromosome 2q23.3 may be
      associated with IS susceptibility among young adults.

PMID- 22384362
TI  - Genome-Scale Analysis of Programmed DNA Elimination Sites in Tetrahymena
      thermophila.
AB  - Genetically programmed DNA rearrangements can regulate mRNA expression at an
      individual locus or, for some organisms, on a genome-wide scale. Ciliates rely on
      a remarkable process of whole-genome remodeling by DNA elimination to
      differentiate an expressed macronucleus (MAC) from a copy of the germline
      micronucleus (MIC) in each cycle of sexual reproduction. Here we describe results
      from the first high-throughput sequencing effort to investigate ciliate genome
      restructuring, comparing Sanger long-read sequences from a Tetrahymena
      thermophila MIC genome library to the MAC genome assembly. With almost 25%
      coverage of the unique-sequence MAC genome by MIC genome sequence reads, we
      created a resource for positional analysis of MIC-specific DNA removal that
      pinpoints MAC genome sites of DNA elimination at nucleotide resolution. The
      widespread distribution of internal eliminated sequences (IES) in promoter
      regions and introns suggests that MAC genome restructuring is essential not only
      for what it removes (for example, active transposons) but also for what it
      creates (for example, splicing-competent introns). Consistent with the
      heterogeneous boundaries and epigenetically modulated efficiency of individual
      IES deletions studied to date, we find that IES sites are dramatically under
      represented in the ~25% of the MAC genome encoding exons. As an exception to this
      general rule, we discovered a previously unknown class of small (<500 bp) IES
      with precise elimination boundaries that can contribute the 3' exon of an mRNA
      expressed during genome restructuring, providing a new mechanism for expanding
      mRNA complexity in a developmentally regulated manner.

PMID- 22384363
TI  - High-Resolution SNP/CGH Microarrays Reveal the Accumulation of Loss of
      Heterozygosity in Commonly Used Candida albicans Strains.
AB  - Phenotypic diversity can arise rapidly through loss of heterozygosity (LOH) or by
      the acquisition of copy number variations (CNV) spanning whole chromosomes or
      shorter contiguous chromosome segments. In Candida albicans, a heterozygous
      diploid yeast pathogen with no known meiotic cycle, homozygosis and aneuploidy
      alter clinical characteristics, including drug resistance. Here, we developed a
      high-resolution microarray that simultaneously detects ~39,000 single nucleotide
      polymorphism (SNP) alleles and ~20,000 copy number variation loci across the C.
      albicans genome. An important feature of the array analysis is a computational
      pipeline that determines SNP allele ratios based upon chromosome copy number.
      Using the array and analysis tools, we constructed a haplotype map (hapmap) of
      strain SC5314 to assign SNP alleles to specific homologs, and we used it to
      follow the acquisition of loss of heterozygosity (LOH) and copy number changes in
      a series of derived laboratory strains. This high-resolution SNP/CGH microarray
      and the associated hapmap facilitated the phasing of alleles in lab strains and
      revealed detrimental genome changes that arose frequently during molecular
      manipulations of laboratory strains. Furthermore, it provided a useful tool for
      rapid, high-resolution, and cost-effective characterization of changes in allele
      diversity as well as changes in chromosome copy number in new C. albicans
      isolates.

PMID- 22384364
TI  - Transposon-Mediated Transgenesis in the Short-Lived African Killifish
      Nothobranchius furzeri, a Vertebrate Model for Aging.
AB  - The African killifish Nothobranchius furzeri is the shortest-lived vertebrate
      that can be bred in captivity. N. furzeri comprises several wild-derived strains
      with striking differences in longevity ranging from 3 to 9 months, which makes it
      a powerful vertebrate model for aging research. The short life cycle of N.
      furzeri should also facilitate studies on adult traits that are specific to
      vertebrates. Although progress has been made to generate a genetic linkage map
      and to start sequencing the genome of N. furzeri, tools to genetically manipulate
      this species of fish have not yet been developed. Here, we report the first
      establishment of transgenesis in N. furzeri. We use the Tol2 transposase system
      to generate transgenic N. furzeri that express green fluorescent protein driven
      by the Xenopus cytoskeletal actin promoter or the zebrafish heat-shock protein 70
      promoter. We successfully generate stable transgenic lines of N. furzeri with
      germline transmission of integrated transgene. The development of transgenesis in
      N. furzeri provides a powerful tool to investigate the mechanisms underlying
      aging and longevity in a short-lived vertebrate model. Transgenesis in this fish
      will also facilitate the study of other phenotypes, including adult tissue
      regeneration and cognitive behavior.

PMID- 22384365
TI  - Genome evolution in the eremothecium clade of the Saccharomyces complex revealed
      by comparative genomics.
AB  - We used comparative genomics to elucidate the genome evolution within the pre
      whole-genome duplication genus Eremothecium. To this end, we sequenced and
      assembled the complete genome of Eremothecium cymbalariae, a filamentous
      ascomycete representing the Eremothecium type strain. Genome annotation indicated
      4712 gene models and 143 tRNAs. We compared the E. cymbalariae genome with that
      of its relative, the riboflavin overproducer Ashbya (Eremothecium) gossypii, and
      the reconstructed yeast ancestor. Decisive changes in the Eremothecium lineage
      leading to the evolution of the A. gossypii genome include the reduction from
      eight to seven chromosomes, the downsizing of the genome by removal of 10% or 900
      kb of DNA, mostly in intergenic regions, the loss of a TY3-Gypsy-type
      transposable element, the re-arrangement of mating-type loci, and a massive
      increase of its GC content. Key species-specific events are the loss of MNN1
      family of mannosyltransferases required to add the terminal fourth and fifth
      alpha-1,3-linked mannose residue to O-linked glycans and genes of the Ehrlich
      pathway in E. cymbalariae and the loss of ZMM-family of meiosis-specific proteins
      and acquisition of riboflavin overproduction in A. gossypii. This reveals that
      within the Saccharomyces complex genome, evolution is not only based on genome
      duplication with subsequent gene deletions and chromosomal rearrangements but
      also on fungi associated with specific environments (e.g. involving fungal-insect
      interactions as in Eremothecium), which have encountered challenges that may be
      reflected both in genome streamlining and their biosynthetic potential.

PMID- 22384366
TI  - Genome-Wide Analysis of Nascent Transcription in Saccharomyces cerevisiae.
AB  - The assessment of transcriptional regulation requires a genome-wide survey of
      active RNA polymerases. Thus, we combined the nuclear run-on assay, which labels
      and captures nascent transcripts, with high-throughput DNA sequencing to examine
      transcriptional activity in exponentially growing Saccharomyces cerevisiae.
      Sequence read data from these nuclear run-on libraries revealed that
      transcriptional regulation in yeast occurs not only at the level of RNA
      polymerase recruitment to promoters but also at postrecruitment steps. Nascent
      synthesis signals are strongly enriched at TSS throughout the yeast genome,
      particularly at histone loci. Nascent transcripts reveal antisense transcription
      for more than 300 genes, with the read data providing support for the activity of
      distinct promoters driving transcription in opposite directions rather than
      bidirectional transcription from single promoters. By monitoring total RNA in
      parallel, we found that transcriptional activity accounts for 80% of the variance
      in transcript abundance. We computed RNA stabilities from nascent and steady
      state transcripts for each gene and found that the most stable and unstable
      transcripts encode proteins whose functional roles are consistent with these
      stabilities. We also surveyed transcriptional activity after heat shock and found
      that most, but not all, heat shock-inducible genes increase their abundance by
      increasing their RNA synthesis. In summary, this study provides a genome-wide
      view of RNA polymerase activity in yeast, identifies regulatory steps in the
      synthesis of transcripts, and analyzes transcript stabilities.

PMID- 22384367
TI  - Unexpected Diversity of Chloroplast Noncoding RNAs as Revealed by Deep Sequencing
      of the Arabidopsis Transcriptome.
AB  - Noncoding RNAs (ncRNA) are widely expressed in both prokaryotes and eukaryotes.
      Eukaryotic ncRNAs are commonly micro- and small-interfering RNAs (18-25 nt)
      involved in posttranscriptional gene silencing, whereas prokaryotic ncRNAs vary
      in size and are involved in various aspects of gene regulation. Given the
      prokaryotic origin of organelles, the presence of ncRNAs might be expected;
      however, the full spectrum of organellar ncRNAs has not been determined
      systematically. Here, strand-specific RNA-Seq analysis was used to identify 107
      candidate ncRNAs from Arabidopsis thaliana chloroplasts, primarily encoded
      opposite protein-coding and tRNA genes. Forty-eight ncRNAs were shown to
      accumulate by RNA gel blot as discrete transcripts in wild-type (WT) plants
      and/or the pnp1-1 mutant, which lacks the chloroplast ribonuclease polynucleotide
      phosphorylase (cpPNPase). Ninety-eight percent of the ncRNAs detected by RNA gel
      blot had different transcript patterns between WT and pnp1-1, suggesting cpPNPase
      has a significant role in chloroplast ncRNA biogenesis and accumulation. Analysis
      of materials deficient for other major chloroplast ribonucleases, RNase R, RNase
      E, and RNase J, showed differential effects on ncRNA accumulation and/or form,
      suggesting specificity in RNase-ncRNA interactions. 5' end mapping demonstrates
      that some ncRNAs are transcribed from dedicated promoters, whereas others result
      from transcriptional read-through. Finally, correlations between accumulation of
      some ncRNAs and the symmetrically transcribed sense RNA are consistent with a
      role in RNA stability. Overall, our data suggest that this extensive population
      of ncRNAs has the potential to underpin a previously underappreciated regulatory
      mode in the chloroplast.

PMID- 22384368
TI  - An Evaluation of Arabidopsis thaliana Hybrid Traits and Their Genetic Control.
AB  - Heterosis is an important phenomenon in agriculture. However, heterosis often
      greatly varies among hybrids and among traits. To investigate heterosis across a
      large number of traits and numerous genotypes, we evaluated 12 life history
      traits on parents and hybrids derived from five Arabidopsis thaliana ecotypes
      (Col, Ler-0, Cvi, Ws, and C24) by using a complete diallel analysis containing 20
      hybrids. Parental contributions to heterosis were hybrid and trait specific with
      a few reciprocal differences. Most notably, C24 generated hybrids with flowering
      time, biomass, and reproductive traits that often exceeded high-parent values.
      However, reproductive traits of C24 and Col hybrids and flowering time traits of
      C24 and Ler hybrids had no heterosis. We investigated whether allelic variation
      at flowering time genes FRIGIDA (FRI) and FLOWERING LOCUS C (FLC) could explain
      the genotype- and trait-specific contribution of C24 to hybrid traits. We
      evaluated both Col and Ler lines introgressed with various FRI and FLC alleles
      and hybrids between these lines and C24. Hybrids with functional FLC differed
      from hybrids with nonfunctional FLC for 21 of the 24 hybrid-trait combinations.
      In most crosses, heterosis was fully or partially explained by FRI and FLC. Our
      results describe the genetic diversity for heterosis within a sample of A.
      thaliana ecotypes and show that FRI and FLC are major factors that contribute to
      heterosis in a genotype and trait specific fashion.

PMID- 22384369
TI  - Major families of multiresistant plasmids from geographically and
      epidemiologically diverse staphylococci.
AB  - Staphylococci are increasingly aggressive human pathogens suggesting that active
      evolution is spreading novel virulence and resistance phenotypes. Large
      staphylococcal plasmids commonly carry antibiotic resistances and virulence loci,
      but relatively few have been completely sequenced. We determined the plasmid
      content of 280 staphylococci isolated in diverse geographical regions from the
      1940s to the 2000s and found that 79% of strains carried at least one large
      plasmid >20 kb and that 75% of these large plasmids were 20-30 kb. Using
      restriction fragment length polymorphism (RFLP) analysis, we grouped 43% of all
      large plasmids into three major families, showing remarkably conserved
      intercontinental spread of multiresistant staphylococcal plasmids over seven
      decades. In total, we sequenced 93 complete and 57 partial staphylococcal
      plasmids ranging in size from 1.3 kb to 64.9 kb, tripling the number of complete
      sequences for staphylococcal plasmids >20 kb in the NCBI RefSeq database. These
      plasmids typically carried multiple antimicrobial and metal resistances and
      virulence genes, transposases and recombinases. Remarkably, plasmids within each
      of the three main families were >98% identical, apart from insertions and
      deletions, despite being isolated from strains decades apart and on different
      continents. This suggests enormous selective pressure has optimized the content
      of certain plasmids despite their large size and complex organization.

PMID- 22384370
TI  - Physical Mapping in a Triplicated Genome: Mapping the Downy Mildew Resistance
      Locus Pp523 in Brassica oleracea L.
AB  - We describe the construction of a BAC contig and identification of a minimal
      tiling path that encompass the dominant and monogenically inherited downy mildew
      resistance locus Pp523 of Brassica oleracea L. The selection of BAC clones for
      construction of the physical map was carried out by screening gridded BAC
      libraries with DNA overgo probes derived from both genetically mapped DNA markers
      flanking the locus of interest and BAC-end sequences that align to Arabidopsis
      thaliana sequences within the previously identified syntenic region. The selected
      BAC clones consistently mapped to three different genomic regions of B. oleracea.
      Although 83 BAC clones were accurately mapped within a ~4.6 cM region surrounding
      the downy mildew resistance locus Pp523, a subset of 33 BAC clones mapped to
      another region on chromosome C8 that was ~60 cM away from the resistance gene,
      and a subset of 63 BAC clones mapped to chromosome C5. These results reflect the
      triplication of the Brassica genomes since their divergence from a common
      ancestor shared with A. thaliana, and they are consonant with recent analyses of
      the C genome of Brassica napus. The assembly of a minimal tiling path constituted
      by 13 (BoT01) BAC clones that span the Pp523 locus sets the stage for map-based
      cloning of this resistance gene.

PMID- 22384371
TI  - Transcription factor binding site redundancy in embryonic enhancers of the
      Drosophila bithorax complex.
AB  - The molecular control of gene expression in development is mediated through the
      activity of embryonic enhancer cis-regulatory modules. This activity is
      determined by the combination of repressor and activator transcription factors
      that bind at specific DNA sequences in the enhancer. A proposed mechanism to
      ensure a high fidelity of transcriptional output is functional redundancy between
      closely spaced binding sites within an enhancer. Here I show that at the bithorax
      complex in Drosophila there is selective redundancy for both repressor and
      activator factor binding sites in vivo. The absence of compensatory binding sites
      is responsible for two rare gain-of-function mutations in the complex.

PMID- 22384372
TI  - A Genetic Screen for Dominant Enhancers of the Cell-Cycle Regulator alpha
      Endosulfine Identifies Matrimony as a Strong Functional Interactor in Drosophila.
AB  - The coordination of cell-cycle events with developmental processes is essential
      for the reproductive success of organisms. In Drosophila melanogaster, meiosis is
      tightly coupled to oocyte development, and early embryos undergo specialized S-M
      mitoses that are supported by maternal products. We previously showed that the
      small phosphoprotein alpha-endosulfine (Endos) is required for normal oocyte
      meiotic maturation and early embryonic mitoses in Drosophila. In this study, we
      performed a genetic screen for dominant enhancers of endos(00003) and identified
      several genomic regions that, when deleted, lead to impaired fertility of
      endos(00003)/+ heterozygous females. We uncovered matrimony (mtrm), which encodes
      a Polo kinase inhibitor, as a strong dominant enhancer of endos. mtrm(126) +/+
      endos(00003) females are sterile because of defects in early embryonic mitoses,
      and this phenotype is reverted by removal of one copy of polo. These results
      provide compelling genetic evidence that excessive Polo activity underlies the
      strong functional interaction between endos(00003) and mtrm(126). Moreover, we
      show that endos is required for the increased expression of Mtrm in mature
      oocytes, which is presumably loaded into early embryos. These data are consistent
      with the model that maternal endos antagonizes Polo function in the early embryo
      to ensure normal mitoses through its effects on Mtrm expression during late
      oogenesis. Finally, we also identified genomic deletions that lead to loss of
      viability of endos(00003)/+ heterozygotes, consistent with recently published
      studies showing that endos is required zygotically to regulate the cell cycle
      during development.

PMID- 22384373
TI  - A Geographically Diverse Collection of Schizosaccharomyces pombe Isolates Shows
      Limited Phenotypic Variation but Extensive Karyotypic Diversity.
AB  - The fission yeast Schizosaccharomyces pombe has been widely used to study
      eukaryotic cell biology, but almost all of this work has used derivatives of a
      single strain. We have studied 81 independent natural isolates and 3 designated
      laboratory strains of Schizosaccharomyces pombe. Schizosaccharomyces pombe varies
      significantly in size but shows only limited variation in proliferation in
      different environments compared with Saccharomyces cerevisiae. Nucleotide
      diversity, pi, at a near neutral site, the central core of the centromere of
      chromosome II is approximately 0.7%. Approximately 20% of the isolates showed
      karyotypic rearrangements as detected by pulsed field gel electrophoresis and
      filter hybridization analysis. One translocation, found in 6 different isolates,
      including the type strain, has a geographically widespread distribution and a
      unique haplotype and may be a marker of an incipient speciation event. All of the
      other translocations are unique. Exploitation of this karyotypic diversity may
      cast new light on both the biology of telomeres and centromeres and on isolating
      mechanisms in single-celled eukaryotes.

PMID- 22384374
TI  - Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence
      from Humans, Mice, and Fruit Flies.
AB  - Alcohol use disorders are influenced by many interacting genetic and
      environmental factors. Highlighting this complexity is the observation that large
      genome-wide association experiments have implicated many genes with weak
      statistical support. Experimental model systems, cell culture and animal, have
      identified many genes and pathways involved in ethanol response, but their
      applicability to the development of alcohol use disorders in humans is
      undetermined. To overcome the limitations of any single experimental system, the
      analytical strategy used here was to identify genes that exert common phenotypic
      effects across multiple experimental systems. Specifically, we (1) performed a
      mouse linkage analysis to identify quantitative trait loci that influence ethanol
      induced ataxia; (2) performed a human genetic association analysis of the mouse
      identified loci against ethanol-induced body sway, a phenotype that is not only
      comparable to the mouse ethanol-ataxia phenotype but is also a genetically
      influenced endophenotype of alcohol use disorders; (3) performed behavioral
      genetic experiments in Drosophila showing that fly homologs of GPC5, the member
      of the glypican gene family implicated by both the human and mouse genetic
      analyses, influence the fly's response to ethanol; and (4) discovered data from
      the literature demonstrating that the genetically implicated gene's expression is
      not only temporally and spatially consistent with involvement in ethanol-induced
      behaviors but is also modulated by ethanol. The convergence of these data
      provides strong support to the hypothesis that GPC5 is involved in cellular and
      organismal ethanol response and the etiology of alcohol use disorders in humans.

PMID- 22384375
TI  - A Novel Retrotransposon Inserted in the Dominant Vrn-B1 Allele Confers Spring
      Growth Habit in Tetraploid Wheat (Triticum turgidum L.).
AB  - Vernalization genes determine winter/spring growth habit in temperate cereals and
      play important roles in plant development and environmental adaptation. In wheat
      (Triticum L. sp.), it was previously shown that allelic variation in the
      vernalization gene VRN1 was due to deletions or insertions either in the promoter
      or in the first intron. Here, we report a novel Vrn-B1 allele that has a
      retrotransposon in its promoter conferring spring growth habit. The VRN-B1 gene
      was mapped in a doubled haploid population that segregated for winter-spring
      growth habit but was derived from two spring tetraploid wheat genotypes, the
      durum wheat (T. turgidum subsp. durum) variety 'Lebsock' and T. turgidum subsp.
      carthlicum accession PI 94749. Genetic analysis revealed that Lebsock carried the
      dominant Vrn-A1 and recessive vrn-B1 alleles, whereas PI 94749 had the recessive
      vrn-A1 and dominant Vrn-B1 alleles. The Vrn-A1 allele in Lebsock was the same as
      the Vrn-A1c allele previously reported in hexaploid wheat. No differences existed
      between the vrn-B1 and Vrn-B1 alleles, except that a 5463-bp insertion was
      detected in the 5'-UTR region of the Vrn-B1 allele. This insertion was a novel
      retrotransposon (designated as retrotrans_VRN), which was flanked by a 5-bp
      target site duplication and contained primer binding site and polypurine tract
      motifs, a 325-bp long terminal repeat, and an open reading frame encoding 1231
      amino acids. The insertion of retrotrans_VRN resulted in expression of Vrn-B1
      without vernalization. Retrotrans_VRN is prevalent among T. turgidum subsp.
      carthlicum accessions, less prevalent among T. turgidum subsp. dicoccum
      accessions, and rarely found in other tetraploid wheat subspecies.

PMID- 22384376
TI  - Specific Cooperation Between Imp-alpha2 and Imp-beta/Ketel in Spindle Assembly
      During Drosophila Early Nuclear Divisions.
AB  - The multifunctional factors Imp-alpha and Imp-beta are involved in nuclear
      protein import, mitotic spindle dynamics, and nuclear membrane formation.
      Furthermore, each of the three members of the Imp-alpha family exerts distinct
      tasks during development. In Drosophila melanogaster, the imp-alpha2 gene is
      critical during oogenesis for ring canal assembly; specific mutations, which
      allow oogenesis to proceed normally, were found to block early embryonic mitosis.
      Here, we show that imp-alpha2 and imp-beta genetically interact during early
      embryonic development, and we characterize the pattern of defects affecting
      mitosis in embryos laid by heterozygous imp-alpha2(D14) and imp-beta(KetRE34)
      females. Embryonic development is arrested in these embryos but is unaffected in
      combinations between imp-beta(KetRE34) and null mutations in imp-alpha1 or imp
      alpha3. Furthermore, the imp-alpha2(D14)/imp-beta(KetRE34) interaction could only
      be rescued by an imp-alpha2 transgene, albeit not imp-alpha1 or imp-alpha3,
      showing the exclusive imp-alpha2 function with imp-beta. Use of transgenes
      carrying modifications in the major Imp-alpha2 domains showed the critical
      requirement of the nuclear localization signal binding (NLSB) site in this
      process. In the mutant embryos, we found metaphase-arrested mitoses made of
      enlarged spindles, suggesting an unrestrained activity of factors promoting
      spindle assembly. In accordance with this, we found that Imp-beta(KetRE34) and
      Imp-beta(KetD) bind a high level of RanGTP/GDP, and a deletion decreasing RanGTP
      level suppresses the imp-beta(KetRE34) phenotype. These data suggest that a fine
      balance among Imp-alpha2, Imp-beta, RanGTP, and the NLS cargos is critical for
      mitotic progression during early embryonic development.

PMID- 22384377
TI  - Whole-Genome Sequencing to Identify Mutants and Polymorphisms in Chlamydomonas
      reinhardtii.
AB  - Whole-genome sequencing (WGS) provides a new platform for the identification of
      mutations that produce a mutant phenotype. We used Illumina sequencing to
      identify the mutational profile of three Chlamydomonas reinhardtii mutant
      strains. The three strains have more than 38,000 changes from the reference
      genome. NG6 is aflagellate and maps to 269 kb with only one nonsynonymous change;
      the V(12)E mutation falls in the FLA8 gene. Evidence that NG6 is a fla8 allele
      comes from swimming revertants that are either true or pseudorevertants. NG30 is
      aflagellate and maps to 458 kb that has six nonsynonomous changes. Evidence that
      NG30 has a causative nonsense allele in IFT80 comes from rescue of the
      nonswimming phenotype with a fragment bearing only this gene. This gene has been
      implicated in Jeune asphyxiating thoracic dystrophy. Electron microscopy of ift80
      1 (NG30) shows a novel basal body phenotype. A bar or cap is observed over the
      distal end of the transition zone, which may be an intermediate in preparing the
      basal body for flagellar assembly. In the acetate-requiring mutant ac17, we
      failed to find a nonsynonymous change in the 676 kb mapped region, which is
      incompletely assembled. In these strains, 43% of the changes occur on two of the
      17 chromosomes. The excess on chromosome 6 surrounds the mating-type locus, which
      has numerous rearrangements and suppressed recombination, and the changes extend
      beyond the mating-type locus. Unexpectedly, chromosome 16 shows an unexplained
      excess of single nucleotide polymorphisms and indels. Overall, WGS in combination
      with limited mapping allows fast and accurate identification of point mutations
      in Chlamydomonas.

PMID- 22384378
TI  - Genetic analysis of fibroblast growth factor signaling in the Drosophila eye.
AB  - The development of eyes in Drosophila involves intricate epithelial
      reorganization events for accurate positioning of cells and proper formation and
      organization of ommatidial clusters. We demonstrate that Branchless (Bnl), the
      fibroblast growth factor ligand, regulates restructuring events in the eye disc
      primordium from as early as the emergence of clusters from a morphogenetic front
      to the cellular movements during pupal eye development. Breathless (Btl)
      functions as the fibroblast growth factor receptor to mediate Bnl signal, and
      together they regulate expression of DE-cadherin, Crumbs, and Actin. In addition,
      in the eye Bnl regulates the temporal onset and extent of retinal basal glial
      cell migration by activating Btl in the glia. We hypothesized that the Bnl
      functions in the eye are Hedgehog dependent and represent novel aspects of Bnl
      signaling not explored previously.

PMID- 22384379
TI  - Natural Genetic Variation for Growth and Development Revealed by High-Throughput
      Phenotyping in Arabidopsis thaliana.
AB  - Leaf growth and development determines a plant's capacity for photosynthesis and
      carbon fixation. These morphological traits are the integration of genetic and
      environmental factors through time. Yet fine dissection of the developmental
      genetic basis of leaf expansion throughout a growing season is difficult, due to
      the complexity of the trait and the need for real time measurement. In this
      study, we developed a time-lapse image analysis approach, which traces leaf
      expansion under seasonal light variation. Three growth traits, rosette leaf area,
      circular area, and their ratio as compactness, were measured and normalized on a
      linear timescale to control for developmental heterogeneity. We found high
      heritability for all growth traits that changed over time. Our study highlights a
      cost-effective, high-throughput phenotyping approach that facilitates the
      dissection of genetic basis of plant shoot growth and development under dynamic
      environmental conditions.

PMID- 22384380
TI  - Linkage and Physical Mapping of Sex Region on LG23 of Nile Tilapia (Oreochromis
      niloticus).
AB  - Evidence supports that sex determination (SD) in tilapia is controlled by major
      genetic factors that may interact with minor genetic as well as environmental
      factors, thus implying that SD should be analyzed as a quantitative trait.
      Quantitative trait loci (QTL) for SD in Oreochromis niloticus were previously
      detected on linkage groups (LG) 1 and 23. Twenty-one short single repeats (SSR)
      of >12 TGs and one single nucleotide polymorphism were identified using the
      unpublished tilapia genome sequence on LG23. All markers showed two segregating
      alleles in a mapping family that was obtained by a cross between O. niloticus
      male (XY) and sex-reversed female (DeltaXY) yielding 29 females (XX) and 61 males
      (XY and YY). Interval mapping analysis mapped the QTL peak between SSR markers
      ARO172 and ARO177 with a maximum F value of 78.7 (P < 7.6 * 10(-14)). Twelve
      adjacent markers found in this region were homozygous in females and either
      homozygous for the alternative allele or heterozygous in males. This segment was
      defined as the sex region (SR). The SR encompasses 1.5 Mbp on a single tilapia
      scaffold (no. 101) harboring 51 annotated genes. Among 10 candidate genes for SD
      that were tested for gene expression, anti-Mullerian hormone (Amh), which is
      located in the center of the SR, showed the highest overexpression in male vs.
      female embryos at 3 to 7 days postfertilization.

PMID- 22384381
TI  - A high-density simple sequence repeat and single nucleotide polymorphism genetic
      map of the tetraploid cotton genome.
AB  - Genetic linkage maps play fundamental roles in understanding genome structure,
      explaining genome formation events during evolution, and discovering the genetic
      bases of important traits. A high-density cotton (Gossypium spp.) genetic map was
      developed using representative sets of simple sequence repeat (SSR) and the first
      public set of single nucleotide polymorphism (SNP) markers to genotype 186
      recombinant inbred lines (RILs) derived from an interspecific cross between
      Gossypium hirsutum L. (TM-1) and G. barbadense L. (3-79). The genetic map
      comprised 2072 loci (1825 SSRs and 247 SNPs) and covered 3380 centiMorgan (cM) of
      the cotton genome (AD) with an average marker interval of 1.63 cM. The
      allotetraploid cotton genome produced equivalent recombination frequencies in its
      two subgenomes (At and Dt). Of the 2072 loci, 1138 (54.9%) were mapped to 13 At
      subgenome chromosomes, covering 1726.8 cM (51.1%), and 934 (45.1%) mapped to 13
      Dt-subgenome chromosomes, covering 1653.1 cM (48.9%). The genetically smallest
      homeologous chromosome pair was Chr. 04 (A04) and 22 (D04), and the largest was
      Chr. 05 (A05) and 19 (D05). Duplicate loci between and within homeologous
      chromosomes were identified that facilitate investigations of chromosome
      translocations. The map augments evidence of reciprocal rearrangement between
      ancestral forms of Chr. 02 and 03 versus segmental homeologs 14 and 17 as
      centromeric regions show homeologous between Chr. 02 (A02) and 17 (D02), as well
      as between Chr. 03 (A03) and 14 (D03). This research represents an important
      foundation for studies on polyploid cottons, including germplasm
      characterization, gene discovery, and genome sequence assembly.

PMID- 22384382
TI  - Genetic analysis in Drosophila reveals a role for the mitochondrial protein p32
      in synaptic transmission.
AB  - Mitochondria located within neuronal presynaptic terminals have been shown to
      play important roles in the release of chemical neurotransmitters. In the present
      study, a genetic screen for synaptic transmission mutants of Drosophila has
      identified the first mutation in a Drosophila homolog of the mitochondrial
      protein P32. Although P32 is highly conserved and has been studied extensively,
      its physiological role in mitochondria remains unknown and it has not previously
      been implicated in neural function. The Drosophila P32 mutant, referred to as
      dp32(EC1), exhibited a temperature-sensitive (TS) paralytic behavioral phenotype.
      Moreover, electrophysiological analysis at adult neuromuscular synapses revealed
      a TS reduction in the amplitude of excitatory postsynaptic currents (EPSC) and
      indicated that dP32 functions in neurotransmitter release. These studies are the
      first to address P32 function in Drosophila and expand our knowledge of
      mitochondrial proteins contributing to synaptic transmission.

PMID- 22384383
TI  - Genome-wide survey of large rare copy number variants in Alzheimer's disease
      among Caribbean hispanics.
AB  - Recently genome-wide association studies have identified significant association
      between Alzheimer's disease (AD) and variations in CLU, PICALM, BIN1, CR1,
      MS4A4/MS4A6E, CD2AP, CD33, EPHA1, and ABCA7. However, the pathogenic variants in
      these loci have not yet been found. We conducted a genome-wide scan for large
      copy number variation (CNV) in a dataset of Caribbean Hispanic origin (554
      controls and 559 AD cases that were previously investigated in a SNP-based genome
      wide association study using Illumina HumanHap 650Y platform). We ran four CNV
      calling algorithms to obtain high-confidence calls for large CNVs (>100 kb) that
      were detected by at least two algorithms. Global burden analyses did not reveal
      significant differences between cases and controls in CNV rate, distribution of
      deletions or duplications, total or average CNV size; or number of genes affected
      by CNVs. However, we observed a nominal association between AD and a ~470 kb
      duplication on chromosome 15q11.2 (P = 0.037). This duplication, encompassing up
      to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1, and WHAMML1) was present in 10
      cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes
      was further confirmed by quantitative PCR. The current study did not detect CNVs
      that affect novel AD loci identified by recent genome-wide association studies.
      However, because the array technology used in our study has limitations in
      detecting small CNVs, future studies must carefully assess novel AD genes for the
      presence of disease-related CNVs.

PMID- 22384384
TI  - Drosophila Reporter Vectors Compatible with PhiC31 Integrase Transgenesis
      Techniques and Their Use to Generate New Notch Reporter Fly Lines.
AB  - Complex spatial and temporal regulation of gene activity is fundamental to
      development and homeostasis. The ability to decipher the DNA sequences that
      accurately coordinate gene expression is, therefore, of primary importance. One
      way to assess the functions of DNA elements entails their fusion to fluorescent
      reporter genes. This powerful approach makes it possible to visualize their
      regulatory capabilities when reintroduced into the developing animal. Transgenic
      studies in Drosophila have recently advanced with the introduction of site
      specific, PhiC31 integrase-mediated approaches. However, most existing Drosophila
      reporter vectors are not compatible with this new approach and have become
      obsolete. Here we describe a new series of fluorescent reporter vectors optimized
      for use with PhiC31 transgenesis. By using these vectors to generate a set of
      Notch reporter fly lines, we demonstrate their efficacy in reporting the function
      of gene regulatory elements.

PMID- 22384385
TI  - Genetic Diversity and Genomic Plasticity of Cryptococcus neoformans AD Hybrid
      Strains.
AB  - Natural hybridization between two strains, varieties, or species is a common
      phenomenon in both plants and animals. Although hybridization may skew
      established gene pools, it generates population diversity efficiently and
      sometimes results in the emergence of newly adapted genotypes. Cryptococcus
      neoformans, which causes the most frequent opportunistic fungal infection in
      immunocompromised hosts, has three serotypes: A, D, and AD. Serotype-specific
      multilocus sequence typing and serotype-specific comparative genome hybridization
      were applied to investigate the genetic variability and genomic organization of
      C. neoformans serotype AD isolates. We confirm that C. neoformans serotype AD
      isolates are hybrids of serotype A and D strains. Compared with haploid strains,
      most AD hybrid isolates exhibit unique multilocus sequence typing genotypes,
      suggesting that multiple independent hybridization events punctuated the origin
      and evolutionary trajectory of AD hybrids. The MATa alleles from both haploid and
      AD hybrid isolates group closely to form a cluster or subcluster in both the
      serotype A and D populations. The rare and unique distribution of MATa alleles
      may restrict sexual reproduction between isolates of opposite mating types. The
      genetic diversity of the serotype D population, including haploid strains and
      serotype D genomes of the AD hybrid, is significantly greater than that of
      serotype A, and there are signatures of recombination within the serotype D
      population. Given that MATa isolates are relatively rare, both opposite-sex and
      same-sex mating may contribute to genetic recombination of serotype D in nature.
      Extensive chromosome loss was observed in AD hybrid isolates, which results in
      loss of heterozygosity in the otherwise-heterozygous AD hybrid genome. Most AD
      hybrid isolates exhibit hybrid vigor and are resistant to the antifungal drug
      FK506. In addition, the C. neoformans AD hybrid genome is highly dynamic, with
      continuous chromosome loss, which may be a facile route for pathogen evolution
      through which genotypic and phenotypic variation is generated.

PMID- 22384386
TI  - The C57BL/6J Mouse Strain Background Modifies the Effect of a Mutation in Bcl2l2.
AB  - Bcl2l2 encodes BCL-W, an antiapoptotic member of the BCL-2 family of proteins.
      Intercross of Bcl2l2 +/- mice on a mixed C57BL/6J, 129S5 background produces
      Bcl2l2 -/- animals with the expected frequency. In contrast, intercross of Bcl2l2
      +/- mice on a congenic C57BL/6J background produces relatively few live-born
      Bcl2l2 -/- animals. Genetic modifiers alter the effect of a mutation. C57BL/6J
      mice (Mus musculus) have a mutant allele of nicotinamide nucleotide
      transhydrogenase (Nnt) that can act as a modifier. Loss of NNT decreases the
      concentration of reduced nicotinamide adenine dinucleotide phosphate within the
      mitochondrial matrix. Nicotinamide adenine dinucleotide phosphate is a cofactor
      for glutathione reductase, which regenerates reduced glutathione, an important
      antioxidant. Thus, loss of NNT activity is associated with increased
      mitochondrial oxidative damage and cellular stress. To determine whether loss of
      Bcl2l2 -/- mice on the C57BL/6J background was mediated by the Nnt mutation, we
      outcrossed Bcl2l2 congenic C57BL/6J (Nnt -/-) mice with the closely related
      C57BL/6JEiJ (Nnt +/+) strain to produce Bcl2l2 +/- ; Nnt +/+ and Bcl2l2 +/- ; Nnt
      -/- animals. Intercross of Bcl2l2 +/- ; Nnt +/+ mice produced Bcl2l2 -/- with the
      expected frequency, whereas intercross of Bcl2l2 +/- ; Nnt -/- animals did not.
      This finding indicates the C57BL/6J strain background, and possibly the Nnt
      mutation, modifies the Bcl2l2 mutant phenotype. This and previous reports
      highlight the importance of knowing the genetic composition of mouse strains used
      in research studies as well as the accurate reporting of mouse strains in the
      scientific literature.

PMID- 22384387
TI  - Strain Variation in the Transcriptome of the Dengue Fever Vector, Aedes aegypti.
AB  - Studies of transcriptome dynamics provide a basis for understanding functional
      elements of the genome and the complexity of gene regulation. The dengue vector
      mosquito, Aedes aegypti, exhibits great adaptability to diverse ecological
      conditions, is phenotypically polymorphic, and shows variation in vectorial
      capacity to arboviruses. Previous genome sequencing showed richness in repetitive
      DNA and transposable elements that can contribute to genome plasticity.
      Population genetic studies revealed a varying degree of worldwide genetic
      polymorphism. However, the extent of functional genetic polymorphism across
      strains is unknown. The transcriptomes of three Ae. aegypti strains, Chetumal
      (CTM), Rexville D-Puerto Rico (Rex-D) and Liverpool (LVP), were compared. CTM is
      more susceptible than Rex- D to infection by dengue virus serotype 2. A total of
      4188 transcripts exhibit either no or small variation (<2-fold) among sugar-fed
      samples of the three strains and between sugar- and blood-fed samples within each
      strain, corresponding most likely to genes encoding products necessary for vital
      functions. Transcripts enriched in blood-fed mosquitoes encode proteins
      associated with catalytic activities, molecular transport, metabolism of lipids,
      carbohydrates and amino acids, and functions related to blood digestion and the
      progression of the gonotropic cycle. Significant qualitative and quantitative
      differences were found in individual transcripts among strains including
      differential representation of paralogous gene products. The majority of immunity
      associated transcripts decreased in accumulation after a bloodmeal and the
      results are discussed in relation to the different susceptibility of CTM and Rex
      D mosquitoes to DENV2 infection.

PMID- 22384388
TI  - Chromosome y regulates survival following murine coxsackievirus b3 infection.
AB  - Coxsackievirus B3 (CVB3) contributes to the development of myocarditis, an
      inflammatory heart disease that predominates in males, and infection is a cause
      of unexpected death in young individuals. Although gonadal hormones contribute
      significantly to sex differences, sex chromosomes may also influence disease.
      Increasing evidence indicates that Chromosome Y (ChrY) genetic variants can
      impact biological functions unrelated to sexual differentiation. Using C57BL/6J
      (B6)-ChrY consomic mice, we show that genetic variation in ChrY has a direct
      effect on the survival of CVB3-infected animals. This effect is not due to
      potential Sry-mediated differences in prenatal testosterone exposure or to
      differences in adult testosterone levels. Furthermore, we show that ChrY
      polymorphism influences the percentage of natural killer T cells in B6-ChrY
      consomic strains but does not underlie CVB3-induced mortality. These data
      underscore the importance of investigating not only the hormonal regulation but
      also ChrY genetic regulation of cardiovascular disease and other male-dominant,
      sexually dimorphic diseases and phenotypes.

PMID- 22384389
TI  - Use of Cumulative Poisson Probability Distribution as an Estimator of the
      Recombination Rate in an Expanding Population: Example of the Macaca fascicularis
      Major Histocompatibility Complex.
AB  - We describe a method to estimate the rate of recombination per generation from
      the genotypes of a large individual sample of an expanding population, for which
      the founding event is dated. The approach is illustrated with an application to
      estimating the major histocompatibility complex (MHC) recombination rate in the
      Mauritian macaque population. We genotyped 750 macaques by means of 17
      microsatellites across the MHC region and reconstructed the seven most frequent
      haplotypes assumed to represent the founding haplotypes (H(rec(0))) as well as
      the 31% recombinant haplotypes (H(rec(h))) resulting from a variable number "h"
      of recombinations between the founding haplotypes. The relative frequencies of
      the various classes of haplotypes (H(rec(0)) and H(rec(h))) follow a Poisson
      distribution. By using a maximum likelihood method, we calculated the mean of the
      Poisson distribution that best fits the data. By dividing this mean by the number
      of generations (50-100) from the date of the population founding, we deduced that
      rate of recombination in the MHC is approximately 0.004 to 0.008 in the Mauritian
      macaque population. When the founding date of the population is precisely known,
      our method presents a useful alternative to the coalescent method.

PMID- 22384390
TI  - Many Saccharomyces cerevisiae Cell Wall Protein Encoding Genes Are Coregulated by
      Mss11, but Cellular Adhesion Phenotypes Appear Only Flo Protein Dependent.
AB  - The outer cell wall of the yeast Saccharomyces cerevisiae serves as the interface
      with the surrounding environment and directly affects cell-cell and cell-surface
      interactions. Many of these interactions are facilitated by specific adhesins
      that belong to the Flo protein family. Flo mannoproteins have been implicated in
      phenotypes such as flocculation, substrate adhesion, biofilm formation, and
      pseudohyphal growth. Genetic data strongly suggest that individual Flo proteins
      are responsible for many specific cellular adhesion phenotypes. However, it
      remains unclear whether such phenotypes are determined solely by the nature of
      the expressed FLO genes or rather as the result of a combination of FLO gene
      expression and other cell wall properties and cell wall proteins. Mss11 has been
      shown to be a central element of FLO1 and FLO11 gene regulation and acts together
      with the cAMP-PKA-dependent transcription factor Flo8. Here we use genome-wide
      transcription analysis to identify genes that are directly or indirectly
      regulated by Mss11. Interestingly, many of these genes encode cell wall
      mannoproteins, in particular, members of the TIR and DAN families. To examine
      whether these genes play a role in the adhesion properties associated with Mss11
      expression, we assessed deletion mutants of these genes in wild-type and
      flo11Delta genetic backgrounds. This analysis shows that only FLO genes, in
      particular FLO1/10/11, appear to significantly impact on such phenotypes. Thus
      adhesion-related phenotypes are primarily dependent on the balance of FLO gene
      expression.

PMID- 22384391
TI  - Multiplex Chromosomal Exome Sequencing Accelerates Identification of ENU-Induced
      Mutations in the Mouse.
AB  - Forward genetic screens in Mus musculus have proved powerfully informative by
      revealing unsuspected mechanisms governing basic biological processes. This
      approach uses potent chemical mutagens, such as N-ethyl-N-nitrosourea (ENU), to
      randomly induce mutations in mice, which are then bred and phenotypically
      screened to identify lines that disrupt a specific biological process of
      interest. Although identifying a mutation using the rich resources of mouse
      genetics is straightforward, it is unfortunately neither fast nor cheap. Here we
      show that detecting newly induced causal variants in a forward genetic screen can
      be accelerated dramatically using a methodology that combines multiplex
      chromosome-specific exome capture, next-generation sequencing, rapid mapping,
      sequence annotation, and variation filtering. The key innovation of our method is
      multiplex capture and sequence that allows the simultaneous survey of both
      mutant, parental, and background strains in a single experiment. By comparing
      variants identified in mutant offspring with those found in dbSNP, the
      unmutagenized background strains, and parental lines, induced causative mutations
      can be distinguished immediately from preexisting variation or experimental
      artifact. Here we demonstrate this approach to find the causative mutations
      induced in four novel ENU lines identified from a recent ENU screen. In all four
      cases, after applying our method, we found six or fewer putative mutations (and
      sometimes only a single one). Determining the causative variant was then easily
      achieved through standard segregation approaches. We have developed this process
      into a community resource that will speed up individual labs' ability to identify
      the genetic lesion in mutant mouse lines; all of our reagents and software tools
      are open source and available to the broader scientific community.

PMID- 22384392
TI  - Facilitating discovery: the role of society journals in collaborative science.

PMID- 22384393
TI  - Ten years of the collaborative cross.
AB  - The February 2012 issues of GENETICS and G3: Genes, Genomes, Genetics present a
      collection of articles reporting recent advances from the international
      Collaborative Cross (CC) project. The goal of the CC project is to develop a new
      resource that will enhance quantitative trait locus (QTL) and systems genetic
      analyses in mice. The CC consists of hundreds of independently bred, octo
      parental recombinant inbred lines (Figure 1). The work reported in these issues
      represents progress toward completion of the CC, proof-of-principle experiments
      using incipient inbred CC mice, and new research areas and complementary
      resources facilitated by the CC project.

PMID- 22384394
TI  - Genetic analysis of hematological parameters in incipient lines of the
      collaborative cross.
AB  - Hematological parameters, including red and white blood cell counts and
      hemoglobin concentration, are widely used clinical indicators of health and
      disease. These traits are tightly regulated in healthy individuals and are under
      genetic control. Mutations in key genes that affect hematological parameters have
      important phenotypic consequences, including multiple variants that affect
      susceptibility to malarial disease. However, most variation in hematological
      traits is continuous and is presumably influenced by multiple loci and variants
      with small phenotypic effects. We used a newly developed mouse resource
      population, the Collaborative Cross (CC), to identify genetic determinants of
      hematological parameters. We surveyed the eight founder strains of the CC and
      performed a mapping study using 131 incipient lines of the CC. Genome scans
      identified quantitative trait loci for several hematological parameters,
      including mean red cell volume (Chr 7 and Chr 14), white blood cell count (Chr
      18), percent neutrophils/lymphocytes (Chr 11), and monocyte number (Chr 1). We
      used evolutionary principles and unique bioinformatics resources to reduce the
      size of candidate intervals and to view functional variation in the context of
      phylogeny. Many quantitative trait loci regions could be narrowed sufficiently to
      identify a small number of promising candidate genes. This approach not only
      expands our knowledge about hematological traits but also demonstrates the unique
      ability of the CC to elucidate the genetic architecture of complex traits.

PMID- 22384395
TI  - Genome-wide association mapping of quantitative traits in outbred mice.
AB  - Recent developments in high-density genotyping and statistical analysis methods
      that have enabled genome-wide association studies in humans can also be applied
      to outbred mouse populations. Increased recombination in outbred populations is
      expected to provide greater mapping resolution than traditional inbred line
      crosses, improving prospects for identifying the causal genes. We carried out
      genome-wide association mapping by using 288 mice from a commercially available
      outbred stock; NMRI mice were genotyped with a high-density single-nucleotide
      polymorphism array to map loci influencing high-density lipoprotein cholesterol,
      systolic blood pressure, triglyceride levels, glucose, and urinary albumin-to
      creatinine ratios. We found significant associations (P < 10(-5)) with high
      density lipoprotein cholesterol and identified Apoa2 and Scarb1, both of which
      have been previously reported, as candidate genes for these associations.
      Additional suggestive associations (P < 10(-3)) identified in this study were
      also concordant with published quantitative trait loci, suggesting that we are
      sampling from a limited pool of genetic diversity that has already been well
      characterized. These findings dampen our enthusiasm for currently available
      commercial outbred stocks as genetic mapping resources and highlight the need for
      new outbred populations with greater genetic diversity. Despite the lack of novel
      associations in the NMRI population, our analysis strategy illustrates the
      utility of methods that could be applied to genome-wide association studies in
      humans.

PMID- 22384396
TI  - HTreeQA: Using Semi-Perfect Phylogeny Trees in Quantitative Trait Loci Study on
      Genotype Data.
AB  - With the advances in high-throughput genotyping technology, the study of
      quantitative trait loci (QTL) has emerged as a promising tool to understand the
      genetic basis of complex traits. Methodology development for the study of QTL
      recently has attracted significant research attention. Local phylogeny-based
      methods have been demonstrated to be powerful tools for uncovering significant
      associations between phenotypes and single-nucleotide polymorphism markers.
      However, most existing methods are designed for homozygous genotypes, and a
      separate haplotype reconstruction step is often needed to resolve heterozygous
      genotypes. This approach has limited power to detect nonadditive genetic effects
      and imposes an extensive computational burden. In this article, we propose a new
      method, HTreeQA, that uses a tristate semi-perfect phylogeny tree to approximate
      the perfect phylogeny used in existing methods. The semi-perfect phylogeny trees
      are used as high-level markers for association study. HTreeQA uses the genotype
      data as direct input without phasing. HTreeQA can handle complex local population
      structures. It is suitable for QTL mapping on any mouse populations, including
      the incipient Collaborative Cross lines. Applied HTreeQA, significant QTLs are
      found for two phenotypes of the PreCC lines, white head spot and running distance
      at day 5/6. These findings are consistent with known genes and QTL discovered in
      independent studies. Simulation studies under three different genetic models show
      that HTreeQA can detect a wider range of genetic effects and is more efficient
      than existing phylogeny-based approaches. We also provide rigorous theoretical
      analysis to show that HTreeQA has a lower error rate than alternative methods.

PMID- 22384397
TI  - Accelerating the inbreeding of multi-parental recombinant inbred lines generated
      by sibling matings.
AB  - Inbred model organisms are powerful tools for genetic studies because they
      provide reproducible genomes for use in mapping and genetic manipulation.
      Generating inbred lines via sibling matings, however, is a costly undertaking
      that requires many successive generations of breeding, during which time many
      lines fail. We evaluated several approaches for accelerating inbreeding,
      including the systematic use of back-crosses and marker-assisted breeder
      selection, which we contrasted with randomized sib-matings. Using simulations, we
      explored several alternative breeder-selection methods and monitored the gain and
      loss of genetic diversity, measured by the number of recombination-induced
      founder intervals, as a function of generation. For each approach we simulated
      100,000 independent lines to estimate distributions of generations to achieve
      full-fixation as well as to achieve a mean heterozygosity level equal to 20
      generations of randomized sib-mating. Our analyses suggest that the number of
      generations to fully inbred status can be substantially reduced with minimal
      impact on genetic diversity through combinations of parental backcrossing and
      marker-assisted inbreeding. Although simulations do not consider all confounding
      factors underlying the inbreeding process, such as a loss of fecundity, our
      models suggest many viable alternatives for accelerating the inbreeding process.

PMID- 22384398
TI  - Haplotype probabilities in advanced intercross populations.
AB  - Advanced intercross populations, in which multiple inbred strains are mated at
      random for many generations, have the advantage of greater precision of genetic
      mapping because of the accumulation of recombination events across the multiple
      generations. Related designs include heterogeneous stock and the diversity
      outcross population. In this article, I derive the two-locus haplotype
      probabilities on the autosome and X chromosome with these designs. These
      haplotype probabilities provide the key quantities for developing hidden Markov
      models for the treatment of missing genotype information. I further derive the
      map expansion in these populations, which is the frequency of recombination
      breakpoints on a random chromosome.

PMID- 22384399
TI  - Transcriptome atlases of mouse brain reveals differential expression across brain
      regions and genetic backgrounds.
AB  - Mouse models play a crucial role in the study of human behavioral traits and
      diseases. Variation of gene expression in brain may play a critical role in
      behavioral phenotypes, and thus it is of great importance to understand
      regulation of transcription in mouse brain. In this study, we analyzed the role
      of two important factors influencing steady-state transcriptional variation in
      mouse brain. First we considered the effect of assessing whole brain vs. discrete
      regions of the brain. Second, we investigated the genetic basis of strain effects
      on gene expression. We examined the transcriptome of three brain regions using
      Affymetrix expression arrays: whole brain, forebrain, and hindbrain in adult mice
      from two common inbred strains (C57BL/6J vs. NOD/ShiLtJ) with eight replicates
      for each brain region and strain combination. We observed significant differences
      between the transcriptomes of forebrain and hindbrain. In contrast, the
      transcriptomes of whole brain and forebrain were very similar. Using 4.3 million
      single-nucleotide polymorphisms identified through whole-genome sequencing of
      C57BL/6J and NOD/ShiLtJ strains, we investigated the relationship between strain
      effect in gene expression and DNA sequence similarity. We found that cis
      regulatory effects play an important role in gene expression differences between
      strains and that the cis-regulatory elements are more often located in 5' and/or
      3' transcript boundaries, with no apparent preference on either 5' or 3' ends.

PMID- 22384400
TI  - Expression quantitative trait Loci for extreme host response to influenza a in
      pre-collaborative cross mice.
AB  - Outbreaks of influenza occur on a yearly basis, causing a wide range of symptoms
      across the human population. Although evidence exists that the host response to
      influenza infection is influenced by genetic differences in the host, this has
      not been studied in a system with genetic diversity mirroring that of the human
      population. Here we used mice from 44 influenza-infected pre-Collaborative Cross
      lines determined to have extreme phenotypes with regard to the host response to
      influenza A virus infection. Global transcriptome profiling identified 2671
      transcripts that were significantly differentially expressed between mice that
      showed a severe ("high") and mild ("low") response to infection. Expression
      quantitative trait loci mapping was performed on those transcripts that were
      differentially expressed because of differences in host response phenotype to
      identify putative regulatory regions potentially controlling their expression.
      Twenty-one significant expression quantitative trait loci were identified, which
      allowed direct examination of genes associated with regulation of host response
      to infection. To perform initial validation of our findings, quantitative
      polymerase chain reaction was performed in the infected founder strains, and we
      were able to confirm or partially confirm more than 70% of those tested. In
      addition, we explored putative causal and reactive (downstream) relationships
      between the significantly regulated genes and others in the high or low response
      groups using structural equation modeling. By using systems approaches and a
      genetically diverse population, we were able to develop a novel framework for
      identifying the underlying biological subnetworks under host genetic control
      during influenza virus infection.

PMID- 22384401
TI  - A Resource of Quantitative Functional Annotation for Homo sapiens Genes.
AB  - The body of human genomic and proteomic evidence continues to grow at ever
      increasing rates, while annotation efforts struggle to keep pace. A surprisingly
      small fraction of human genes have clear, documented associations with specific
      functions, and new functions continue to be found for characterized genes. Here
      we assembled an integrated collection of diverse genomic and proteomic data for
      21,341 human genes and make quantitative associations of each to 4333 Gene
      Ontology terms. We combined guilt-by-profiling and guilt-by-association
      approaches to exploit features unique to the data types. Performance was
      evaluated by cross-validation, prospective validation, and by manual evaluation
      with the biological literature. Functional-linkage networks were also
      constructed, and their utility was demonstrated by identifying candidate genes
      related to a glioma FLN using a seed network from genome-wide association
      studies. Our annotations are presented-alongside existing validated annotations
      in a publicly accessible and searchable web interface.

PMID- 22384402
TI  - Extent With Modification: Leg Patterning in the Beetle Tribolium castaneum and
      the Evolution of Serial Homologs.
AB  - Serial homologs are similar structures that develop at different positions within
      a body plan. These structures share some, but not all, aspects of developmental
      patterning, and their evolution is thought to be constrained by shared,
      pleiotropic gene functions. Here we describe the functions of 17 developmental
      genes during metamorphic development of the legs in the red flour beetle,
      Tribolium castaneum. This study provides informative comparisons between
      appendage development in Drosophila melanogaster and T. castaneum, between
      embryonic and adult development in T. castaneum, and between the development of
      serially homologous appendages. The leg gap genes Distal-less and dachshund are
      conserved in function. Notch signaling, the zinc-finger transcription factors
      related to odd-skipped, and bric-a-brac have conserved functions in promoting
      joint development. homothorax knockdown alters the identity of proximal leg
      segments but does not reduce growth. Lim1 is required for intermediate leg
      development but not distal tarsus and pretarsus development as in D.
      melanogaster. Development of the tarsus requires decapentaplegic, rotund,
      spineless, abrupt, and bric-a-brac and the EGF ligand encoded by Keren.
      Metathoracic legs of T. castaneum have four tarsomeres, whereas other legs have
      five. Patterns of gene activity in the tarsus suggest that patterning in the
      middle of the tarsal region, not the proximal- or distal-most areas, is
      responsible for this difference in segment number. Through comparisons with other
      recent studies of T. castaneum appendage development, we test hypotheses for the
      modularity or interdependence of development during evolution of serial homologs.

PMID- 22384403
TI  - A Whole-Chromosome Analysis of Meiotic Recombination in Drosophila melanogaster.
AB  - Although traditional genetic assays have characterized the pattern of crossing
      over across the genome in Drosophila melanogaster, these assays could not
      precisely define the location of crossovers. Even less is known about the
      frequency and distribution of noncrossover gene conversion events. To assess the
      specific number and positions of both meiotic gene conversion and crossover
      events, we sequenced the genomes of male progeny from females heterozygous for
      93,538 X chromosomal single-nucleotide and InDel polymorphisms. From the analysis
      of the 30 F1 hemizygous X chromosomes, we detected 15 crossover and 5
      noncrossover gene conversion events. Taking into account the nonuniform
      distribution of polymorphism along the chromosome arm, we estimate that most
      oocytes experience 1 crossover event and 1.6 gene conversion events per X
      chromosome pair per meiosis. An extrapolation to the entire genome would predict
      approximately 5 crossover events and 8.6 conversion events per meiosis. Mean gene
      conversion tract lengths were estimated to be 476 base pairs, yielding a per
      nucleotide conversion rate of 0.86 * 10(-5) per meiosis. Both of these values are
      consistent with estimates of conversion frequency and tract length obtained from
      studies of rosy, the only gene for which gene conversion has been studied
      extensively in Drosophila. Motif-enrichment analysis revealed a GTGGAAA motif
      that was enriched near crossovers but not near gene conversions. The low
      complexity and frequent occurrence of this motif may in part explain why, in
      contrast to mammalian systems, no meiotic crossover hotspots have been found in
      Drosophila.

PMID- 22384404
TI  - Whole-Genome Sequencing of Sordaria macrospora Mutants Identifies Developmental
      Genes.
AB  - The study of mutants to elucidate gene functions has a long and successful
      history; however, to discover causative mutations in mutants that were generated
      by random mutagenesis often takes years of laboratory work and requires
      previously generated genetic and/or physical markers, or resources like DNA
      libraries for complementation. Here, we present an alternative method to identify
      defective genes in developmental mutants of the filamentous fungus Sordaria
      macrospora through Illumina/Solexa whole-genome sequencing. We sequenced pooled
      DNA from progeny of crosses of three mutants and the wild type and were able to
      pinpoint the causative mutations in the mutant strains through bioinformatics
      analysis. One mutant is a spore color mutant, and the mutated gene encodes a
      melanin biosynthesis enzyme. The causative mutation is a G to A change in the
      first base of an intron, leading to a splice defect. The second mutant carries an
      allelic mutation in the pro41 gene encoding a protein essential for sexual
      development. In the mutant, we detected a complex pattern of
      deletion/rearrangements at the pro41 locus. In the third mutant, a point mutation
      in the stop codon of a transcription factor-encoding gene leads to the production
      of immature fruiting bodies. For all mutants, transformation with a wild type
      copy of the affected gene restored the wild-type phenotype. Our data demonstrate
      that whole-genome sequencing of mutant strains is a rapid method to identify
      developmental genes in an organism that can be genetically crossed and where a
      reference genome sequence is available, even without prior mapping information.

PMID- 22384405
TI  - Narrowing Down the Mapping of Plant Sex-Determination Regions Using New Y
      Chromosome-Specific Markers and Heavy-Ion Beam Irradiation-Induced Y-Deletion
      Mutants in Silene latifolia.
AB  - Silene latifolia is a well-studied model system for plant XY sex determination.
      Three maleness factors are thought to function on the Y chromosome, gynoecium
      suppression factor (GSF), stamen-promoting factor (SPF), and male fertility
      factor (MFF), and their deletions result in hermaphrodites, anther defects, and
      pollen defects, respectively. Although a framework map of the Y chromosome
      exists, the sex determination genes have not been identified, and no markers
      close enough to potentially be used for BAC library screening are yet available.
      The analysis of Y deletion mutants by Y-chromosome-specific STS markers is an
      efficient way to isolate sex determination regions, but more Y-specific STS
      markers are needed to accelerate the exploration of sex determination factors.
      Herein, we report a marker design method that uses simple sequence repeats, which
      is especially effective on the Y chromosome of S. latifolia because it contains
      many simple sequence repeats. Six new Y-chromosome-specific STS markers were
      obtained, SmicSy1-6. These were used to detect relatively small Y deletion sites
      in heavy-ion beam irradiation-induced mutants. The mapping of male sex
      determination regions was narrowed down by using more markers and smaller-sized Y
      deletion mutants. One new marker, SmicSy6, is a proximal marker to SPF and, thus,
      a second index for SPF. The region including SPF is thought to be located between
      two SPF proximal markers. The flower phenotype correlates with the deletion size
      of SPF using SPF proximal markers. These findings represent new progress in
      isolating the sex determination factor, which has been studied for more than 50
      years.

PMID- 22384406
TI  - Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype.
AB  - Basal cell carcinomas (BCCs) are the most common cancers in the United States.
      The histologic appearance distinguishes several subtypes, each of which can have
      a different biologic behavior. In this study, global miRNA expression was
      quantified by high-throughput sequencing in nodular BCCs, a subtype that is slow
      growing, and infiltrative BCCs, aggressive tumors that extend through the dermis
      and invade structures such as cutaneous nerves. Principal components analysis
      correctly classified seven of eight infiltrative tumors on the basis of miRNA
      expression. The remaining tumor, on pathology review, contained a mixture of
      nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely
      reflecting broader histopathologic diversity in this class, but trended toward
      forming a group separate from infiltrative BCCs. Quantitative polymerase chain
      reaction assays were developed for six of the miRNAs that showed significant
      differences between the BCC subtypes, and five of these six were validated in a
      replication set of four infiltrative and three nodular tumors. The expression
      level of miR-183, a miRNA that inhibits invasion and metastasis in several types
      of malignancies, was consistently lower in infiltrative than nodular tumors and
      could be one element underlying the difference in invasiveness. These results
      represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene
      expression may be involved in tumor pathogenesis and particularly in determining
      the aggressiveness of these malignancies.

PMID- 22384407
TI  - Physical and Linkage Maps for Drosophila serrata, a Model Species for Studies of
      Clinal Adaptation and Sexual Selection.
AB  - Drosophila serrata is a member of the montium group, which contains more than 98
      species and until recently was considered a subgroup within the melanogaster
      group. This Drosophila species is an emerging model system for evolutionary
      quantitative genetics and has been used in studies of species borders, clinal
      variation and sexual selection. Despite the importance of D. serrata as a model
      for evolutionary research, our poor understanding of its genome remains a
      significant limitation. Here, we provide a first-generation gene-based linkage
      map and a physical map for this species. Consistent with previous studies of
      other drosophilids we observed strong conservation of genes within chromosome
      arms homologous with D. melanogaster but major differences in within-arm synteny.
      These resources will be a useful complement to ongoing genome sequencing efforts
      and QTL mapping studies in this species.

PMID- 22384409
TI  - Evolution of a large, conserved, and syntenic gene family in insects.
AB  - The Osiris gene family, first described in Drosophila melanogaster, is clustered
      in the genomes of all Drosophila species sequenced to date. In D. melanogaster,
      it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient
      locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one
      of the largest syntenic blocks in the Drosophila group. By examining the genome
      sequences of other insects in a wide range of taxonomic orders, we show here that
      the gene family is well-conserved and syntenic not only in the diptera but across
      the holometabolous and hemimetabolous insects. Osiris gene homologs have also
      been found in the expressed sequence tag sequences of various other insects but
      are absent from all groups that are not insects, including crustacea and
      arachnids. It is clear that the gene family evolved by gene duplication and
      neofunctionalization very soon after the divergence of the insects from other
      arthropods but before the divergence of the insects from one another and that the
      sequences and synteny have been maintained by selection ever since.

PMID- 22384408
TI  - Pichia sorbitophila, an Interspecies Yeast Hybrid, Reveals Early Steps of Genome
      Resolution After Polyploidization.
AB  - Polyploidization is an important process in the evolution of eukaryotic genomes,
      but ensuing molecular mechanisms remain to be clarified. Autopolyploidization or
      whole-genome duplication events frequently are resolved in resulting lineages by
      the loss of single genes from most duplicated pairs, causing transient gene
      dosage imbalance and accelerating speciation through meiotic infertility.
      Allopolyploidization or formation of interspecies hybrids raises the problem of
      genetic incompatibility (Bateson-Dobzhansky-Muller effect) and may be resolved by
      the accumulation of mutational changes in resulting lineages. In this article, we
      show that an osmotolerant yeast species, Pichia sorbitophila, recently isolated
      in a concentrated sorbitol solution in industry, illustrates this last situation.
      Its genome is a mosaic of homologous and homeologous chromosomes, or parts
      thereof, that corresponds to a recently formed hybrid in the process of
      evolution. The respective parental contributions to this genome were
      characterized using existing variations in GC content. The genomic changes that
      occurred during the short period since hybrid formation were identified (e.g.,
      loss of heterozygosity, unilateral loss of rDNA, reciprocal exchange) and
      distinguished from those undergone by the two parental genomes after separation
      from their common ancestor (i.e., NUMT (NUclear sequences of MiTochondrial
      origin) insertions, gene acquisitions, gene location movements, reciprocal
      translocation). We found that the physiological characteristics of this new yeast
      species are determined by specific but unequal contributions of its two parents,
      one of which could be identified as very closely related to an extant Pichia
      farinosa strain.

PMID- 22384410
TI  - Small GTPases and formins in mammalian oocyte maturation: cytoskeletal
      organizers.
AB  - The maturation process of mammalian oocytes accompanies an extensive
      rearrangement of the cytoskeleton and associated proteins. As this process
      requires a delicate interplay between the cytoskeleton and its regulators, it is
      often targeted by various external and internal adversaries that affect the
      congression and/or segregation of chromosomes. Asymmetric cell division in
      oocytes also requires specific regulators of the cytoskeleton, including formin-2
      and small GTPases. Recent literature providing clues regarding how actin
      filaments and microtubules interact during spindle migration in mouse oocytes are
      highlighted in this review.

PMID- 22384411
TI  - Genetic association study of a single nucleotide polymorphism of kallikrein
      related peptidase 2 with male infertility.
AB  - OBJECTIVE: To investigate a kallikrein-related peptidase 2 (KLK2) single
      nucleotide polymorphism (SNP) in relation to male infertility because of its role
      in semen processing. We investigated the genetic association of the KLK2+255G>A
      genotype with male infertility. METHODS: We genotyped the SNP site located in
      intron 1 (+255G>A, rs2664155) of KLK2 from 218 men with male infertility (cases)
      and 220 fertile males (controls). Pyrosequencing analysis was performed for the
      genotyping. RESULTS: The SNP of the KLK2 gene had a statistically significant
      association with male infertility (p<0.05). The odds ratio for the minor allele
      (+255A) in the pooled sample was 0.47 (95% confidence intervals, 0.26-0.85) for
      rs2664155. CONCLUSION: The relationship of KLK2 SNP to male infertility is
      statistically significant, especially within the non-azoospermia group. Further
      study is needed to understand the mechanisms associated with male infertility.

PMID- 22384412
TI  - Integrity of human sperm DNA assessed by the neutral comet assay and its
      relationship to semen parameters and clinical outcomes for the IVF-ET program.
AB  - OBJECTIVE: To explore potential relationships between sperm DNA integrity and
      both semen parameters and clinical outcomes. METHODS: Semen analysis of 498
      samples was performed according to the 2010 criteria of the World Health
      Organization. The sperm DNA fragmentation Index (DFI) of the semen samples was
      assessed using a neutral comet assay. RESULTS: Sperm DFI showed a significant
      correlation with semen parameters, including the patient's age, sperm viability,
      motility, morphology, and number of leukocytes (p<0.05). The sperm DFI values for
      asthenozoospermic (15.2%), oligoteratozoospermic (18.3%), asthenoteratozoospermic
      (17.5%), and oligoasthenoteratozoospermic semen samples (21.3%) were
      significantly higher than that observed in normozoospermic semen samples (10.5%,
      p<0.05). A sperm DFI value of 14% was used as a threshold of sperm DFI in
      assessing whether DNA was highly damaged. In 114 IVF-ET cycles, the fertilization
      rate of the sperm DFI <14% group (70 cycles, 61.7%) was significantly higher than
      that observed for the >=14% group (44 cycles, 55.3%), but there was no difference
      in the other clinical outcomes between the two groups. In the >=14% group, the
      pregnancy rates of the ICSI cycles (40.0%) and half-ICSI (44.0%) were higher than
      conventional IVF cycles (30.7%), but the difference was not statistically
      significant. CONCLUSION: Along with the conventional semen analysis, the sperm
      DFI assessed using the comet assay was shown to improve the quality of the semen
      evaluation. To evaluate the precise effect of ICSI on pregnancy rates in the
      patients who demonstrate high sperm DFI values, further study is necessary.

PMID- 22384413
TI  - Expression of peroxiredoxin I regulated by gonadotropins in the rat ovary.
AB  - OBJECTIVE: Peroxiredoxins (Prxs) play an important role in regulating cellular
      differentiation and proliferation in several types of mammalian cells. This
      report examined the expression of Prx isotype I in the rat ovary after hormone
      treatment. METHODS: Immature rats were injected with 10 IU of pregnant mare's
      serum gonadotropin (PMSG) to induce the growth of multiple preovulatory follicles
      and 10 IU of human chorionic gonadotropin (hCG) to induce ovulation. Immature
      rats were also treated with diethylstilbestrol (DES), an estrogen analogue, to
      induce the growth of multiple immature follicles. Northern blot analysis was
      performed to detect gene expression. Cell-type specific localization of Prx I
      mRNA were detected by in situ hybridization analysis. RESULTS: During follicle
      development, ovarian Prx I gene expression was detected in 3-day-old rats and had
      increased in 21-day-old rats. The levels of Prx I mRNA slightly declined one to
      two days following treatment with DES. A gradual increase in Prx I gene
      expression was observed in ovaries obtained from PMSG-treated immature rats.
      Furthermore, hCG treatment of PMSG-primed rats resulted in a gradual stimulation
      of Prx I mRNA levels by 24 hours (2.1-fold increase) following treatment, which
      remained high until 72 hours following treatment. In situ hybridization analysis
      revealed the expression of the Prx I gene in the granulosa cells of PMSG-primed
      ovaries and in the corpora lutea of ovaries stimulated with hCG for 72 hours.
      CONCLUSION: These results demonstrate the gonadotropin and granulosa cell
      specific stimulation of Prx I gene expression, suggesting its role as a local
      regulator of follicle development.

PMID- 22384414
TI  - Effects of various combinations of cryoprotectants and cooling speed on the
      survival and further development of mouse oocytes after vitrification.
AB  - OBJECTIVE: The objectives of this study were to analyze efficacy of immature and
      mature mouse oocytes after vitrification and warming by applying various
      combinations of cryoprotectants (CPAs) and/or super-rapid cooling using slush
      nitrogen (SN(2)). METHODS: Four-week old ICR female mice were superovulated for
      GV- and MII-stage oocytes. Experimental groups were divided into two groups.
      Ethylene glycol (EG) only group: pre-equilibrated with 1.5 M EG for 2.5 minutes
      and then equilibrated with 5.5 M EG and 1.0 M sucrose for 20 seconds.
      EG+dimethylsulfoxide (DMSO) group: pre-equilibrated with 1.3 M EG+1.1 M DMSO for
      2.5 minutes and equilibrated with 2.7 M EG+2.1 M DMSO+0.5 M sucrose for 20
      seconds. The oocytes were loaded onto grids and plunged into SN(2) or liquid
      nitrogen (LN(2)). Stored oocytes were warmed by a five-step method, and then
      their survival, maturation, cleavage, and developmental rates were observed.
      RESULTS: The EG only and EG+DMSO groups showed no significant difference in
      survival of immature oocytes vitrified after warming. However, maturation and
      cleavage rates after conventional insemination were greater in the EG only group
      than in the EG+DMSO group. In mature oocytes, survival, cleavage, and blastocyst
      formation rates after warming showed no significant difference when EG only or
      EG+DMSO was applied. Furthermore, cleavage and blastocyst formation rates of MII
      oocytes vitrified using SN(2) were increased in both the EG only and EG+DMSO
      groups. CONCLUSION: A combination of CPAs in oocyte cryopreservation could be
      formulated according to the oocyte stage. In addition, SN(2) may improve the
      efficiency of vitrification by reducing cryoinjury.

PMID- 22384415
TI  - Does blastomere biopsy in preimplantation genetic diagnosis affect early serum
      beta-hCG levels?
AB  - OBJECTIVE: To determine whether the serum beta-human chorionic gonadotropin (hCG)
      profile following preimplantation genetic diagnosis (PGD) is lower than that of
      intracytoplasmic sperm injection (ICSI) cycles. METHODS: A total of 129 PGD
      cycles and 1,161 age-matched ICSI cycles, which resulted in pregnancy (serum beta
      hCG>=5 mIU/mL) on post-ovulation day (POD) 12 were included. We compared the mean
      serum beta-hCG levels on POD 12, 14, 21, and 28, doubling time of serum hCG, and
      created a cut-off value for predicting a singleton pregnancy in each group.
      RESULTS: The mean serum beta-hCG concentration of the PGD group was significantly
      lower than that of the control group on POD 12, 14, and 21. The doubling time of
      serum beta-hCG at each time interval showed no significant difference. The cut
      off-value of serum beta-hCG for predicting a single viable pregnancy was 32.5
      mIU/mL on POD 12 and 113.5 mIU/mL on POD 14 for the PGD group, which was lower
      than that for the control group. CONCLUSION: Blastomere biopsy may decrease the
      beta-hCG-producing activity of the trophoblasts, especially in early pregnancy.
      Setting a lower cut-off value of serum beta-hCG for predicting pregnancy outcomes
      in PGD may be needed.

PMID- 22384416
TI  - Comparison of follitropin beta administered by a pen device with follitropin beta
      administered by a conventional syringe in patients undergoing IVF-ET.
AB  - OBJECTIVE: To compare the effectiveness and convenience of a pen device for the
      self-administration of follitropin beta with a conventional syringe delivering
      follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist
      long protocol was used for controlled ovarian stimulation (COS) in all subjects.
      A total of 100 patients were randomized into the pen device group or the
      conventional syringe group on the first day of COS. Local tolerance reactions
      were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On
      the day of hCG injection, patients were asked to rate their overall pain and
      convenience experienced with self-injection on a visual anlaogue scale (VAS).
      RESULTS: There were no differences in patients' characteristics between the two
      groups. The duration of COS was significantly shorter in the pen device group
      than in the conventional syringe group. Patients included in the pen device group
      needed a significantly smaller amount of follitropin beta. However, no
      differences between the two groups were found in IVF results and pregnancy
      outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours
      after the injection was significantly lower in the pen device group. VAS scores
      indicated that injections using the pen device were significantly less painful
      and more convenient. CONCLUSION: The pen device for self-administration of
      follitropin beta is less painful, safer and more convenient for the patients, and
      can be more effective because of the shorter duration and smaller dose of
      follitropin beta when compared with the conventional syringe.

PMID- 22384417
TI  - Endometrial histology and predictable clinical factors for endometrial disease in
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: This study was aimed to investigate endometrial histology and to find
      predictable clinical factors for endometrial disease (hyperplasia or cancer) in
      women with polycystic ovary syndrome (PCOS). METHODS: We investigated the
      endometrial histology and analyzed the relationship between endometrial histology
      and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2
      hours postprandial glucose and insulin, insulin resistance, body mass index,
      endometrial thickness, menstrual status from 117 women with PCOS. Statistical
      analysis was performed with chi square and t-test, p-value<0.05 was considered as
      statistically significant. And receiver operating characteristic curve was used
      to find predictable clinical factors for endometrial disease and to decide the
      cuff off values. RESULTS: In 117 women with PCOS, endometrial histologic profiles
      are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia
      in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with
      endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia
      without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%),
      6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were
      significantly related with endometrial disease, p=0.013 and p=0.001,
      respectively. At the cut off level of 25.5 years in age, sensitivity and
      specificity predicting for endometrial disease were 70.4% and 55.6%, respectively
      (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity
      and specificity were 77.8% and 56.7%, respectively (p=0.000). CONCLUSION: In
      women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4%
      and 1.7%. The age and endometrial thickness may be used as clinical determining
      factors for endometrial biopsy.

PMID- 22384418
TI  - Predictive value of sperm motility characteristics assessed by computer-assisted
      sperm analysis in intrauterine insemination with superovulation in couples with
      unexplained infertility.
AB  - OBJECTIVE: To determine whether characteristics of sperm motility obtained by
      computer-assisted sperm analysis (CASA) could predict pregnancy after
      intrauterine insemination (IUI) in couples with unexplained infertility. METHODS:
      Three hundred eighty-three cycles of intrauterine insemination with
      superovulation were retrospectively analyzed. Semen analysis was performed with
      CASA before and after swim-up and the parameters were compared between pregnant
      and non-pregnant women. RESULTS: The pregnancy rate per cycle was 14.1%. Pregnant
      and non-pregnant women were comparable in terms of age, infertility duration, the
      number of dominant follicles. While sperm concentration, motility, and parameters
      such as average path velocity (VAP) and percentage rapid (RAPID) before semen
      preparation were significantly different between the pregnancy and non-pregnancy
      groups, there were no differences in sperm parameters when comparing the two
      groups after preparation. Using a receiver operating characteristic curve to
      measure sensitivity and specificity, the optimal threshold value for the
      predictors of pregnancy was revealed to be a concentration of >=111*10(6)/mL, a
      motility of >=51.4%, and RAPID >=30.1% before preparation for IUI. CONCLUSION:
      Sperm parameters including concentration, motility, and RAPID before sperm
      preparation could have predictive value for pregnancy outcome after intrauterine
      insemination with superovulation in couples with unexplained infertility, and
      would be helpful when counseling patients before they make the decision to
      proceed with IVF/ICSI-ET.

PMID- 22384419
TI  - Comparison of elective single cleavage-embryo transfer to elective single
      blastocyst-embryo transfer in human IVF-ET.
AB  - OBJECTIVE: This study was carried out to compare the clinical outcome of elective
      single cleavage-embryo transfer (eSCET) to that of elective single blastocyst
      embryo transfer (eSBET) in human IVF-ET. METHODS: This study was a retrospective
      study which analyzed for 614 women who visited the Daegu Maria Clinic from August
      2008 to December 2009. All were under 37 years old and had more than 8 mm of
      endometrial thickness on the day of hCG administration and at least one good
      quality embryo on day 3. The eSCETs were performed on day 3 (n=450) and the
      eSBETs were conducted on day 5 (n=164). RESULTS: The numbers of retrieved
      oocytes, fertilized oocytes, and day 3 good quality embryos were significantly
      lower in the eSCET group (12.1+/-6.0, 8.2+/-4.6, and 4.2+/-3.1, respectively)
      compared to the eSBET group (16.7+/-7.2, 12.1+/-5.0, and 8.5+/-4.5, respectively;
      p<0.001). However, the clinical pregnancy, implantation, on-going pregnancy, and
      live birth rates of the eSCET group (46.7, 46.9, 40.0, and 36.7%, respectively)
      were not statistically different from those of the eSBET group (51.2, 51.8, 45.1,
      and 43.9%, respectively; p=0.318, 0.278, 0.254, and 0.103, respectively).
      CONCLUSION: These results suggested that elective single embryo transfer should
      be performed regardless of the developmental stage to women less than 37 years
      old who had more than 8 mm of endometrial thickness on the hCG administration day
      and at least one good quality embryo on day 3 in order to reduce the twin
      pregnancy rate without reducing the whole pregnancy rate.

PMID- 22384420
TI  - Functions of PIWI proteins in spermatogenesis.
AB  - Recently, a significant understanding of the molecular mechanisms regulating
      spermatogenesis has been achieved utilizing small RNA molecules (small RNAs),
      including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi
      interacting RNAs (piRNAs) which emerged as important regulators of gene
      expression at the post-transcriptional or translation level. piRNAs are only
      present in pachytene spermatocytes and round spermatids, whereas miRNAs are
      expressed abundantly in male germ cells throughout spermatogenesis. This review
      is aimed at providing a glimpse of piRNAs and their interacting family proteins
      such as PIWIL1, PIWIL2, and PIWIL4 in spermatogenesis.

PMID- 22384421
TI  - Changes in gene expression associated with oocyte meiosis after Obox4 RNAi.
AB  - OBJECTIVE: Previously, we found that oocyte specific homeobox (Obox) 4 plays
      significant role in completion of meiosis specifically at meiosis I-meiosis II
      (MI-MII) transition. The purpose of this study was to determine the mechanism of
      action of Obox4 in oocyte maturation by evaluating downstream signal networking.
      METHODS: The Obox4 dsRNA was prepared by in vitro transcription and microinjected
      into the cytoplasm of germinal vesicle oocytes followed by in vitro maturation in
      the presence or absence of 0.2 mM 3-isobutyl-1-metyl-xanthine. Total RNA was
      extracted from 200 oocytes of each group using a PicoPure RNA isolation kit then
      amplified two-rounds. The probe hybridization and data analysis were used by
      Affymetrix GeneChip(r) Mouse Genome 430 2.0 array and GenPlex 3.0 (ISTECH, Korea)
      software, respectively. RESULTS: Total 424 genes were up (n=80) and down (n=344)
      regulated after Obox4 RNA interference (RNAi). Genes mainly related to metabolic
      pathways and mitogen-activated protein kinase (MAPK) signaling pathway was
      changed. Among the protein kinase C (PKC) isoforms, PKC-alpha, beta, gamma were
      down-regulated and especially the MAPK signaling pathway PKC-gamma was
      dramatically decreased by Obox4 RNAi. In the cell cycle pathway, we evaluated the
      expression of genes involved in regulation of chromosome separation, and found
      that these genes were down-regulated. It may cause the aberrant chromosome
      segregation during MI-MII transition. CONCLUSION: From the results of this study,
      it is concluded that Obox4 is important upstream regulator of the PKC and
      anaphase-promoting complex action for maintaining intact germinal vesicle.

PMID- 22384422
TI  - Effects of early prepubertal exposure to bisphenol A on the onset of puberty,
      ovarian weights, and estrous cycle in female mice.
AB  - OBJECTIVE: Bisphenol A (BPA) is a chemical used extensively to manufacture
      plastics and epoxy resin liners for food and beverage cans. BPA, with properties
      similar to estrogen, has endocrine-disrupting effects. In the present study, we
      examined the effects of early prepubertal BPA exposure on the onset of puberty
      and reproductive parameters such as estrous cycle and reproductive organ weights
      in female mice. METHODS: Female mice were injected subcutaneously at postnatal
      day (PND) 8 with BPA (0.1, 1, 10, 100 mg/kg) in sesame oil or with sesame oil
      alone. Body weight was measured from PND 10 to 70. Vaginal opening and estrous
      cycle were monitored from PND 20 to 29. Animals were sacrificed at PND 25, 30,
      and 70, and the ovary and uterus weights were measured. RESULTS: Early
      prepubertal exposure to BPA (10 and 100 mg/kg) significantly decreased body
      weight from PND 18 to 30. BPA treated mice at testing dose levels showed early
      opening of the vagina compared to the control group. The number of estrous cycle
      and days of estrus were significantly decreased in high dose (100 mg/kg) BPA
      treated mice. The ovary weight at PND 25 and 30 was significantly decreased in
      all BPA treatment groups. CONCLUSION: Early prepubertal exposure to BPA
      accelerated the onset of puberty but decreased reproductive parameters in female
      mice.

PMID- 22384423
TI  - Sperm nuclear DNA fragmentation and chromatin structure in one-day-old ejaculated
      sperm.
AB  - OBJECTIVE: To evaluate sperm nuclear DNA fragmentation and chromatin structure
      after 18 hours'incubation at room temperature. METHODS: Twenty-eight male
      partners who participating IVF treatment were prospectively included in this
      study. Ejaculated sperm count and motility were assessed. The sperm was then
      immediately processed by the conventional swim-up method. After utilization of
      some of the sample for routine clinical use, the remainder of each of the samples
      was divided into two aliquots. One aliquot was immediately assessed for sperm
      nuclear DNA fragmentation (TUNEL assay) and chromatin structure (toluidine blue
      [TB] staining). The other aliquot was incubated at room temperature for 18 hours
      and then assessed by two methods. Only dark-TB sperms were considered as having
      abnormal chromatin structure. Data before and after extended incubation were
      compared using a paired Student's t-test. RESULTS: Before and after extended
      culture, nuclear DNA fragmentation assessed by TUNEL was 4.9+/-4.7% and 7.0+/
      6.4%, respectively (p=0.008). The proportion of abnormal chromatin structure
      (dark-TB sperm) was 8.2+/-5.6% and 10.3+/-6.5% (p<0.001), before and after
      incubation, respectively. CONCLUSION: After 18 hours' incubation at room
      temperature, sperm nuclear DNA and chromatin structure were significantly
      affected. The IVF practitioner should bear this information in mind when
      performing delayed insemination, especially for in vitro maturation cycles.

PMID- 22384424
TI  - Effect of artificial shrinkage on clinical outcome in fresh blastocyst transfer
      cycles.
AB  - OBJECTIVE: This study aimed to determine the safety and clinical effect of
      artificial shrinkage (AS) in terms of assisted hatching of fresh blastocysts.
      Also, we evaluated the correlation between patient age and the effect of AS on
      clinical outcome. METHODS: Two AS methods, using a 29-gauge needle and laser
      pulse, were compared. Seventy-three blastocysts were shrunk using a 29-gauge
      needle and the same number of other blastocysts were shrunk by a laser pulse. We
      evaluated the shrunken blastocysts hourly and considered them viable if they re
      expanded >70%. Blastocyst transfer cycles (n=134) were divided into two groups: a
      control group consisted of the cycles whose intact embryos were transferred
      (n=100), while the AS group consisted of the cycles whose embryos were replaced
      following AS (n=34). The implantation and pregnancy rates of the control group
      and AS group were compared (p<0.05). RESULTS: The re-expansion rates of the 29
      gauge needle and laser pulse AS groups were similar (56 [76.7%] vs. 62 [84.9%],
      respectively). All of the remaining shrunken blastocysts were re-expanded within
      2 hours. There was no degeneration of shrunken blastocysts. The total and
      clinical pregnancy rate of the AS group (23 [67.6%]; 20 [58.8%], respectively)
      was significantly higher than that of the control group (47 [47.0%]; 39 [39.0%],
      respectively). In the older patient group, there was no difference in the
      clinical outcomes between the AS and control groups. CONCLUSION: These results
      suggest that AS of blastocoele cavity, followed by the transfer, would be a
      useful approach to improve the clinical outcome in cycles in which fresh
      blastocyst stage embryos are transferred.

PMID- 22384425
TI  - Age specific serum anti-Mullerian hormone levels in 1,298 Korean women with
      regular menstruation.
AB  - OBJECTIVE: To determine the age specific serum anti-Mullerian hormone (AMH)
      reference values in Korean women with regular menstruation. METHODS: Between May,
      2010 and January, 2011, the serum AMH levels were evaluated in a total of 1,298
      women who have regular menstrual cycles aged between 20 and 50 years. Women were
      classified into 6 categories by age: 20-31 years, 32-34 years, 35-37 years, 38-40
      years, 41-43 years, above 43 years. Measurement of serum AMH was measured by
      commercial enzyme-linked immunoassay. RESULTS: The serum AMH levels correlated
      negatively with age. The median AMH level of each age group was 4.20 ng/mL, 3.70
      ng/mL, 2.60 ng/mL, 1.50 ng/mL, 1.30 ng/mL, and 0.60 ng/mL, respectively. The AMH
      values in the lower 5th percentile of each age group were 1.19 ng/mL, 0.60 ng/mL,
      0.42 ng/mL, 0.27 ng/mL, 0.14 ng/mL, and 0.10 ng/mL, respectively. CONCLUSION:
      This study determined reference values of serum AMH in Korean women with regular
      menstruation. These values can be applied to clinical evaluation and treatment of
      infertile women.

PMID- 22384426
TI  - Pioglitazone treatment decreases follicular fluid levels of tumor necrosis factor
      alpha and interleukin-6 in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the effects of pioglitazone on controlled ovarian
      stimulation (COS), IVF outcomes, and follicular fluid (FF) cytokine
      concentrations in patients with polycystic ovary syndrome (PCOS). METHODS: Eighty
      six infertile patients with PCOS resistant to clomiphene citrate were randomized
      to receive pioglitazone (30 mg/day) or placebo on the starting day of oral
      contraceptive (OC) pretreatment, followed by an IVF protocol using a GnRH
      antagonist. Pioglitazone or placebo was administered once daily from the starting
      day of OC to the day of hCG injection. RESULTS: Total dose and days of
      recombinant follicle-stimulating hormone administered, and the numbers of
      retrieved and mature oocytes, were significantly lower in the pioglitazone group
      than in the control group. FF tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) concentrations at oocyte retrieval were also significantly
      lower in the pioglitazone group. The clinical pregnancy rate was higher and the
      incidence of severe ovarian hyperstimulation syndrome was lower in the
      pioglitazone group, but the differences were not statistically significant.
      CONCLUSION: Pioglitazone reduces FF TNF-alpha and IL-6 levels, and may improve
      ovarian response to COS in patients with PCOS.

PMID- 22384427
TI  - Adverse pregnancy outcomes with assisted reproductive technology in non-obese
      women with polycystic ovary syndrome: a case-control study.
AB  - OBJECTIVE: To investigate adverse pregnancy outcomes in non-obese women with
      polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups.
      METHODS: Women with PCOS who underwent assisted reproductive technology (ART)
      from August, 2003 to December, 2007, were considered. A total of 336 women with
      PCOS were included in the study group and 1,003 infertile women who had tubal
      factor as an indication for ART were collected as controls. They were divided
      into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal
      factor group, and obese tubal factor group, with obesity defined by a body mass
      index over 25 kg/m(2), and reviewed focusing on the basal characteristics, ART
      outcomes, and adverse pregnancy outcomes. RESULTS: There was no difference among
      the groups' the clinical pregnancy rate or live birth rate. Regarding adverse
      pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence
      of preterm delivery and pregnancy induced hypertension were not different among
      the four groups. The incidence of small for gestational age infant was higher in
      the PCOS groups than the tubal factor groups (p<0.02). On the other hand, the
      morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese
      PCOS group but was in the obese groups. And in the obese PCOS group, the newborns
      were heavier than in the other groups (p<0.02). CONCLUSION: Non-obese PCOS
      presents many differences compared with obese PCOS, not only in the IVF
      parameters but also in the morbidity of adverse pregnancy outcomes, especially in
      GDM and fetal macrosomia.

PMID- 22384428
TI  - Laparoscopic management of early primary peritoneal pregnancy: a case report.
AB  - Peritoneal pregnancy is an implantation in the peritoneal cavity exclusive of
      tubal, ovarian, or intra-ligamentary implantations. This is a rare obstetric
      complication with high maternal mortality and even higher perinatal mortality,
      and secondary type was most common. Risk factors for peritoneal pregnancy are
      previous history of extrauterine pregnancy or tubal surgery pelvic post
      inflammatory status or presence of an intra-uterine device. As it is a life
      threatening condition, expectant management carries a risk of sudden life
      threatening intra-abdominal bleeding and a generally poor fetal prognosis. So,
      when it is recognized, immediate termination of pregnancy is usually recommended.
      Early diagnosis of peritoneal pregnancy is difficult, but is important by their
      life threatening progress course to patients. Recently, we experienced primary
      peritoneal pregnancy which meets both the original and modified criteria. In this
      paper, we reported the case of early diagnosed and successfully treated
      peritoneal pregnancy despite of their diagnosis was incidentally.

PMID- 22384429
TI  - A large advanced seminoma in an older woman with androgen insensitivity syndrome.
AB  - A 58-year-old woman who presented with inguinal hernia for the first time was
      diagnosed as seminoma and complete androgen insensitivity syndrome (CAIS). The
      patient received a late diagnosis, and therefore she could not take a proper
      management. CAIS is a rare X-linked recessive disease with an XY karyotype that
      is caused by androgen receptor defects. It usually present with primary
      amenorrhea or inguinal hernia. The risk of malignant transformation of
      undescended testis increases with age, thus gonadectomy should be performed after
      puberty. We present a case of large advanced seminoma in a woman with CAIS who
      was neglected and diagnosed lately.

PMID- 22384430
TI  - Role of endometrial immune cells in implantation.
AB  - Implantation of an embryo occurs during the mid-secretory phase of the menstrual
      cycle, known as the "implantation window." During this implantation period, there
      are significant morphologic and functional changes in the endometrium, which is
      followed by decidualization. Many immune cells, such as dendritic and natural
      killer (NK) cells, increase in number in this period and early pregnancy. Recent
      works have revealed that antigen-presenting cells (APCs) and NK cells are
      involved in vascular remodeling of spiral arteries in the decidua and lack of
      APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role
      in the induction of immune tolerance during pregnancy. A balance between
      effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and
      regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment
      and maintenance of pregnancy. The highly complicated endocrine-immune network
      works in decidualization of the endometrium and at the fetomaternal interface. We
      will discuss the role of immune cells in the implantation period and during early
      pregnancy.

PMID- 22384431
TI  - An update of preimplantation genetic diagnosis in gene diseases, chromosomal
      translocation, and aneuploidy screening.
AB  - Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of
      gene diseases and chromosomal abnormalities. Much improvement has been achieved
      in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase
      diagnostic accuracy and reduce allele dropout. It is cost-effective and currently
      plays an important role. Whole genome amplification permits subsequent individual
      detection of multiple gene loci and screening all 23 pairs of chromosomes. For
      PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is
      traditionally used, but with technical difficulty. Array comparative genomic
      hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may
      replace FISH. Single nucleotide polymorphisms array with haplotyping can further
      distinguish between normal chromosomes and balanced translocation. PGD may
      shorten time to conceive and reduce miscarriage for patients with chromosomal
      translocation. PGD has a potential value for mitochondrial diseases.
      Preimplantation genetic haplotyping has been applied for unknown mutation sites
      of single gene disease. Preimplantation genetic screening (PGS) using limited
      FISH probes in the cleavage-stage embryo did not increase live birth rates for
      patients with advanced maternal age, unexplained recurrent abortions, and
      repeated implantation failure. Polar body and blastocyst biopsy may circumvent
      the problem of mosaicism. PGS using blastocyst biopsy and array CGH is
      encouraging and merit further studies. Cryopreservation of biopsied blastocysts
      instead of fresh transfer permits sufficient time for transportation and genetic
      analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome
      and possible suboptimal endometrium.

PMID- 22384432
TI  - Expression of SDF-1alpha and leptin, and their effect on expression of angiogenic
      factors in mouse ovaries.
AB  - OBJECTIVE: Ovarian angiogenesis plays an important role in folliculogenesis.
      However, little is known about the expression of angiogenic factors during
      follicular development according to female age. Stromal cell derived factor
      1alpha (SDF-1alpha) plays a role in granulosa cell survival and embryo quality as
      an angiogenic chemokine. Leptin is also involved in folliculogenesis and
      angiogenesis. This study examined expression of SDF-1alpha and leptin, and their
      effects on the expression of angiogenic factors in the ovary during follicular
      development according to female age. METHODS: Ovaries were collected from C57BL
      mice of two age groups (6-9 weeks and 24-26 weeks) at 6, 12, 24, and 48 hours
      after 5 IU pregnant mare's serum gonadotropin (PMSG) injection. The expression of
      ovarian SDF-1alpha and leptin mRNA was evaluated by RT-PCR. In the organ culture
      experiment, the ovaries were cultured in transwell permeable supports with
      Waymouth's medium treated with various doses of SDF-1alpha (50-200 ng/mL) or
      leptin (0.01-1 ug/mL) for 7 days. Then, mRNA expression of vascular endothelial
      growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and visfatin were
      examined in the cultured ovaries. RESULTS: Expression of SDF-1alpha and leptin in
      the ovary was significantly lower in the aged mouse group compared to the young
      mouse group (p<0.05). Expression of these two factors increased with follicular
      development after PMSG administration. SDF-1alpha treatment stimulated visfatin
      expression in a dose-dependent manner, while leptin treatment significantly
      increased eNOS expression. CONCLUSION: These results suggest that decrease of
      ovarian SDF-1alpha and leptin expression may be associated with aging-related
      reduction of ovarian function. SDF-1alpha and leptin may play a role in
      follicular development by regulating the expression of angiogenic factors in
      mouse ovaries.

PMID- 22384433
TI  - Efficacy of testicular sperm chromatin condensation assay using aniline blue
      eosin staining in the IVF-ET cycle.
AB  - OBJECTIVE: This study was performed to evaluate testicular sperm chromatin
      condensation using aniline blue-eosin (AB-E) staining and its effects on IVF-ET.
      METHODS: Chromatin condensation was analyzed using AB-E staining in 27 cases of
      testicular sperm extraction. There were 19 cases of obstructive azoospermia (OA)
      and 8 cases of non-obstructive azoospermia (NOA) in IVF-ET. Mature sperm heads
      were stained red-pink whereas immature sperm heads were stained dark blue. The
      percentage of sperm chromatin condensation was calculated from the ratio of the
      number of red-pink sperm to the total number of sperm analyzed. RESULTS: The
      overall percentages of chromatin condensation in OA and NOA were 31.1+/-11.2% and
      26.3+/-14.4%, respectively. The fertilization rate was significant higher in OA
      than NOA (p<0.05); however, the rates of good embryos and clinical pregnancy did
      not show statistical differences. In OA and NOA, statistical differences were not
      observed in the rate of chromatin condensation, fertilization, good embryos, and
      clinical pregnancy between the pregnant group and non-pregnant group. CONCLUSION:
      Chromatin condensation is less stable than OA and showed a low fertilization rate
      in NOA. While there were no significant differences in chromatin condensation
      results between NOA and OA, we propose that a pattern of decreased chromatin
      condensation in NOA is one of the factors of low fertilization results requiring
      further study.

PMID- 22384434
TI  - Efficiency of laser-assisted intracytoplasmic sperm injection in a human assisted
      reproductive techniques program.
AB  - OBJECTIVE: Laser-assisted intracytoplasmic sperm injection (LA-ICSI), also known
      as micro-opening or thinning of the zona pellucida (ZP) prior to ICSI, may help
      to reduce mechanical damage to the oocyte during the procedure. The aim of the
      present study was to evaluate and analyze the efficacy of our institutional LA
      ICSI program, which features laser-assisted ZP thinning prior to ICSI, in
      comparison with conventional ICSI (C-ICSI), performed on patients with different
      clinical characteristics. METHODS: Patients undergoing a total of 212 ICSI cycles
      were randomly divided into an LA-ICSI group (106 cycles) and a conventional ICSI
      group (106 cycles). To reduce tissue damage, we thinned the ZP by approximately
      70%, using a laser, before ICSI. Patients thus treated formed the LA-ICSI group.
      Comparisons included the morphological quality of transferred embryos, blastocyst
      development of the remaining embryos, and clinical pregnancy, in terms of ICSI
      method and patient characteristics. RESULTS: Fertilization, development of
      remaining embryos, and pregnancy rate were significantly higher in the LA-ICSI
      group compared with the C-ICSI group. Fertilization, embryonic development, and
      the pregnancy rate were all improved in younger patients (<38 years of age) and
      in those who underwent a low number of IVF-ET attempts (<3 trials). In addition,
      the pregnancy rate was increased in older patients. CONCLUSION: LA-ICSI may be
      useful in improving the chance of pregnancy in all ICSI patients.

PMID- 22384435
TI  - Serum anti-Mullerian hormone levels as a predictor of the ovarian response and
      IVF outcomes.
AB  - OBJECTIVE: The aim of this study was to investigate whether anti-Mullerian
      hormone (AMH) levels could be predict ovarian poor/hyper response and IVF cycle
      outcome. METHODS: Between May 2010 and January 2011, serum AMH levels were
      evaluated with retrospective analysis. Three hundred seventy infertile women
      undergoing 461 IVF cycles between the ages of 20 and 42 were studied. We defined
      the poor response as the number of oocytes retrieved was equal or less than 3,
      and the hyper response as more than 25 oocytes retrieved. Serum AMH was measured
      by commercial enzyme-linked immunoassay. RESULTS: The number of oocytes retrieved
      was more correlated with the serum AMH level (r=0.781, p<0.01) than serum FSH (r=
      0.412, p<0.01). The cut-off value of serum AMH levels for poor response was 1.05
      ng/mL (receiver operating characteristic [ROC] curves/area under the curve [AUC],
      ROC(AUC)=0.85, sensitivity 74%, specificity 87%). Hyper response cut-off value
      was 3.55 ng/mL (ROC(AUC)=0.91, sensitivity 94%, specificity 81%). When the study
      group was divided according to the serum AMH levels (low: <1.05 ng/mL, middle:
      1.05 ng/mL - 3.55 ng/mL, high: >3.55 ng/mL), the groups showed no statistical
      differences in mature oocyte rates (71.6% vs. 76.5% vs. 74.8%) or fertilization
      rates (76.9% vs. 76.6% vs. 73.8%), but showed significant differences in clinical
      pregnancy rates (21.7% vs. 24.1% vs. 40.8%, p=0.017). CONCLUSION: The serum AMH
      level can be used to predict the number of oocytes retrieved in patients,
      distinguishing poor and high responders.

PMID- 22384436
TI  - Comparison of mild ovarian stimulation with conventional ovarian stimulation in
      poor responders.
AB  - OBJECTIVE: To compare the IVF outcomes of mild ovarian stimulation with
      conventional ovarian stimulation in poor responders. METHODS: From 2004 to 2009,
      389 IVF cycles in 285 women showed poor responses (defined as either a basal FSH
      level >=12 mIU/mL, or the number of retrieved oocytes <=3, or serum E(2) level on
      hCG day <500 pg/mL) were analyzed, retrospectively. In total, 119 cycles with
      mild ovarian stimulation (m-IVF) and 270 cycles with conventional ovarian
      stimulation (c-IVF) were included. Both groups were divided based on their age,
      into groups over and under 37 years old. RESULTS: The m-IVF group was lower than
      the c-IVF group in the duration of stimulation, total doses of gonadotropins
      used, serum E(2) level on hCG day, the number of retrieved oocytes, and the
      number of mature oocytes. However, there was no significant difference in the
      number of good embryos, the number of transferred embryos, the cancellation rate,
      or the clinical pregnancy rate. In the m-IVF group over 37 years old, the
      clinical pregnancy rate and live birth rate were higher when compared with the c
      IVF group, but this result was not statistically significant. CONCLUSION: In poor
      responder groups, mild ovarian stimulation is more cost effective and patient
      friendly than conventional IVF. Therefore, we suggest that mild ovarian
      stimulation could be considered for poor responders over 37 years old.

PMID- 22384437
TI  - Significance of the serum CA-125 level in intrauterine insemination cycles.
AB  - OBJECTIVE: There are limited data regarding the significance of elevated serum CA
      125 level during IUI cycles, even though it is used widely during the initial
      evaluation of infertile patients. The aim of this study was to investigate the
      prognostic value of serum CA-125 levels during IUI cycles. METHODS: Among the
      patients with controlled ovarian stimulation and IUI cycles at Seoul National
      University Hospital from Jan 2005 through Dec 2009, 92 cases with no identified
      endometriotic lesion, ovarian tumor, salpingeal lesion, or uterine myoma were
      selected. To compare the clinical characteristics between the pregnancy group and
      the non-pregnancy group, the Mann-Whitney U test and Fisher's exact test were
      used. RESULTS: The overall pregnancy rate was 18.5% (17/92). The pregnancy group
      showed a higher number of follicles 16 mm in diameter (p=0.036), endometrial
      thickness (p<0.001), ampules of gonadotropin (p=0.009), and higher body mass
      index (p=0.022) than the non-pregnancy group. No significant difference was
      observed in the serum CA-125 level or the proportion of patients with CA-125
      exceeding 17 IU/mL between the two groups. CONCLUSION: The prognostic value of
      serum CA-125 level among infertile patients with IUI cycles is considered
      limited.

PMID- 22384438
TI  - The role of methylenetetrahydrofolate reductase C677T polymorphism on the
      peripheral blood natural killer cell proportion in women with unexplained
      recurrent miscarriages.
AB  - OBJECTIVE: To examine the association between methylenetetrahydrofolate reductase
      (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained
      recurrent miscarriages (RM) and to investigate the association between MTHFR
      genotype variants and alloimmune activation, proportion of peripheral blood
      natural killer (pbNK) cells. METHODS: A total of 39 patients with a history of
      two or more unexplained miscarriages were recruited to this study. The controls
      were women who had a live birth without a history of RM (n=50). The proportion of
      pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the
      incidence of the MTHFR variant of the RM and control groups were compared. The
      proportion of pbNK cells was compared to the MTHFR variants in the RM group.
      RESULTS: No differences were found between the two groups' mean plasma
      homocysteine levels (7.6+/-1.5 umol/L vs. 7.1+/-2.1 umol/L) or incidence of the
      MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%).
      In the RM group, individuals with the TT variant (7.7+/-1.1 umol/L) had higher
      homocysteine levels than those with the CC and CT variants (7.4+/-1.9 umol/L and
      7.4+/-1.2 umol/L) and those with the CT variant (19.2+/-8.1%) had a higher
      proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants
      (17.7+/-6.6% and 17.9+/-7. 0%), but the results of both comparisons were
      statistically insignificant. CONCLUSION: These preliminary results show no
      difference in plasma homocysteine levels between the RM and control groups or
      among MTHFR genotype variants in the RM group, which may suggest that the plasma
      homocysteine level is difficult to use as a predictive marker of RM in the Korean
      population. A study of a larger number of patients is needed.

PMID- 22384439
TI  - Pulmonary and retroperitoneal benign metastasizing leiomyoma.
AB  - Benign metastasizing leiomyoma (BML) is a rare disease, which usually occurs in
      women with a history of a prior hysterectomy or myomectomy for benign uterine
      leiomyoma, and has the potential to metastasize to distant sites, such as the
      lung, lymph nodes, muscular tissue, heart, or retroperitoneum. These lesions are
      slow-growing, asymptomatic, and usually found incidentally. The prognosis of BML
      is also excellent. However, there has been debate on the origin and the correct
      classification of BML, and there are no guidelines for the treatment of BML. We
      report here on a rare case of BML in both the retroperitoneal cavity and lung in
      a 48-year-old woman with a history of hysterectomy due to histologically benign
      uterine leiomyoma. The patient underwent retroperitoneal mass excision and
      bilateral salpingo-oophorectomy, and then wedge biopsy of two pulmonary nodules
      was performed additionally 9 days later. Until now, there has been no sign of
      recurrence and the patient remains asymptomatic. To our knowledge, pulmonary BML
      is rare and the co-existence of the retroperitoneal metastases after previous
      hysterectomy is even rarer.

PMID- 22384440
TI  - Hormonal regulation of uterine chemokines and immune cells.
AB  - The ultimate function of the endometrium is to allow the implantation of a
      blastocyst and to support pregnancy. Cycles of tissue remodeling ensure that the
      endometrium is in a receptive state during the putative 'implantation window',
      the few days of each menstrual cycle when an appropriately developed blastocyst
      may be available to implant in the uterus. A successful pregnancy requires strict
      temporal regulation of maternal immune function to accommodate a semi-allogeneic
      embryo. To preparing immunological tolerance at the onset of implantation, tight
      temporal regulations are required between the immune and endocrine networks. This
      review will discuss about the action of steroid hormones on the human endometrium
      and particularly their role in regulating the inflammatory processes associated
      with endometrial receptivity.

PMID- 22384441
TI  - Application of two different synthetic sequential media for the human IVF-ET
      program: a prospective, randomized, and comparative study.
AB  - OBJECTIVE: Since IVF program was first established, various types of media and
      culture systems have been developed either in-house or commercially. The aim of
      this study was to compare the efficacy of in-house Maria Research Center (MRC)
      media to that of commercially available Sydney IVF media in human day 3 embryo
      transfer cycles. METHODS: Three hundred sixty nine couples were included in this
      prospective, randomized, and comparative study. All couples undergoing IVF
      treatment at the Maria Fertility Hospital were randomly assigned to either Sydney
      IVF (n=178) or MRC (n=191) media. RESULTS: No difference was observed between the
      MRC media and Sydney IVF media groups with respect to fertilization rate (74.4%
      vs. 75.5%). The clinical pregnancy and implantation rates of MRC media (47.1% and
      20.0%, respectively) were also similar to those of Sydney IVF media (44.4% and
      19.4%, respectively). However, the proportion of embryos with good quality on day
      3 was significantly higher in the MRC media group than the Sydney IVF media group
      (50.2% vs. 43.2%) (p<0.05). CONCLUSION: MRC media were as effective as Sydney IVF
      media for sustaining embryo development and pregnancy rates. The present study
      implies that MRC media can be a suitable alternative to commercially available
      media for human IVF-ET program.

PMID- 22384442
TI  - Expression of interferon regulatory factor-1 in the mouse cumulus-oocyte complex
      is negatively related with oocyte maturation.
AB  - OBJECTIVE: We found previously that interferon regulatory factor (Irf)-1 is a
      germinal vesicle (GV)-selective gene that highly expressed in GV as compared to
      metaphase II oocytes. To our knowledge, the function of Irf-1 in oocytes has yet
      to be examined. The present study was conducted to determine the relationship
      between retinoic acid (RA) and RA-mediated expression of Irf-1 and the mouse
      oocyte maturation. METHODS: Immature cumulus-oocyte-complexes (COCs) were
      collected from 17-day-old female mice and cultured in vitro for 16 hours in the
      presence of varying concentrations of RA (0-10 uM). Rate of oocyte maturation and
      activation was measured. Gene expression was measured by quantitative real-time
      reverse transcription-polymerase chain reaction (RT-PCR) and cytokine secretion
      in the medium was measured by Bio-Plex analysis. Apoptosis was analyzed by
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
      RESULTS: The rates of oocyte maturation to metaphase II and oocyte activation
      increased significantly with RA treatment (10 nM-1 uM). With 100 nM RA treatment,
      lowest level of Irf-1 mRNA and cumulus cell's apoptosis was found. Among 23
      cytokines measured by Bio-Plex system, the substantial changes in secretion of
      tumor necrosis factor-alpha, macrophage inflammatory protein-1beta, eotaxin and
      interleukin-12 (p40) from COCs in response to RA were detected. CONCLUSION: We
      concluded that the maturation of oocytes and Irf-1 expression are negatively
      correlated, and RA enhances the developmental competence of mouse immature
      oocytes in vitro by suppressing apoptosis of cumulus cells. Using a mouse model,
      results of the present study provide insights into improved culture conditions
      for in vitro oocyte maturation and relevant cytokine production and secretion in
      assisted reproductive technology.

PMID- 22384443
TI  - In vitro development and gene expression of frozen-thawed 8-cell stage mouse
      embryos following slow freezing or vitrification.
AB  - OBJECTIVE: This study was performed to compare the efficiency of slow freezing
      and vitrification based on survival, development to blastocysts, and cell numbers
      of blastocysts. Changes in embryonic gene expression in fresh and frozen-thawed
      embryos were also examined. METHODS: Eight-cell stage embryos were collected from
      superovulated female BDF1 mice. The collected embryos were randomly divided into
      three groups. One group was maintained as fresh controls (n=42), one was frozen
      by slow freezing (n=43), and one was cooled by vitrification (n=43). After
      thawing or cooling, survival rates, development to blastocyst, and cell numbers
      and inner cell mass (ICM) cell numbers of blastocysts were compared with those of
      the control group. The expressions of eight genes (Rbm3, Birc5, Sod1, Sod2,
      Cirbp, Caspase3, Trp53, Hsp70.1) were examined by real time-quantitative
      polymerase chain reaction in the fresh and frozen-thawed embryos. RESULTS: There
      were no significant differences in the slow freezing and vitrification groups'
      survival rate after thawing (88.4% vs. 88.4%), development to blastocyst (100%
      vs. 97.4%), cell numbers (107.0+/-21.0 vs. 115.0+/-19.7), or ICM cell numbers of
      blastocysts (11.3+/-5.2 vs. 11.1+/-3.7). Cell numbers of blastocysts were
      significantly (p<0.05) lower in the frozen-thawed embryos than the fresh embryos.
      There were no significant differences in the slow freezing and the vitrification
      groups' expressions of the eight genes. The expressions of CirbP and Hsp70.1 were
      higher in the frozen-thawed embryos than in the fresh embryos but there were no
      significant differences. CONCLUSION: These results suggest that there were no
      significant differences between embryos that underwent slow freezing and
      vitrification.

PMID- 22384444
TI  - Lower growth factor expression in follicular fluid undergone in-vitro
      fertilization.
AB  - OBJECTIVE: This study was performed to identify whether growth and
      differentiation factor-9 (GDF-9) and transforming growth factor-beta1 (TGF-beta1)
      expressions would be lower in the follicular fluid (FF) of those over age 35 who
      underwent IVF than under age 35. METHODS: A total of 24 IVF cycles (20 patients)
      were included in this study. All of patients were stimulated for IVF by the GnRH
      short protocol and divided into two groups for analysis, according to their age:
      <35 group (14 cycles, 11 patients) vs. >=35 group (10 cycles, 9 patients). The
      expression levels of GDF-9 and TGF-beta1 were determined by western blotting and
      quantitative enzyme-linked immunosorbent assay. RESULTS: The numbers of retrieved
      oocytes and metaphase II oocytes were significantly lower in the >=35 group.
      Lower expression of GDF-9 and TGF-beta1 by western blotting in the >=35 group
      were observed as well. The mean GDF-9 and TGF-beta1 levels by enzyme-linked
      immunosorbent assay were lower in the >=35 group. The values were 6,850.5+/-928.4
      ng/L vs. 3,333.3+/-1,089.2 ng/L of GDF-9 (p<0.05) and 3,844.1+/-571.1 ng/L vs.
      2,187.7+/-754.0 ng/L of TGF-beta1 (p<0.05). A negative correlation between GDF-9
      and age was observed (r=-0.546, p=0.006). CONCLUSION: GDF-9 and TGF-beta1
      production from stimulated ovaries during IVF appears to decrease with age.

PMID- 22384445
TI  - Subretinal transplantation of putative retinal pigment epithelial cells derived
      from human embryonic stem cells in rat retinal degeneration model.
AB  - OBJECTIVE: To differentiate the human embryonic stem cells (hESCs) into the
      retinal pigment epithelium (RPE) in the defined culture condition and determine
      its therapeutic potential for the treatment of retinal degenerative diseases.
      METHODS: The embryoid bodies were formed from hESCs and attached on the matrigel
      coated culture dishes. The neural structures consisting neural precursors were
      selected and expanded to form rosette structures. The mechanically isolated
      neural rosettes were differentiated into pigmented cells in the media comprised
      of N2 and B27. Expression profiles of markers related to RPE development were
      analyzed by reverse transcription-polymerase chain reaction and immunostaining.
      Dissociated putative RPE cells (10(5) cells/5 uL) were transplanted into the
      subretinal space of rat retinal degeneration model induced by intravenous sodium
      iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after
      transplantation, and immnohistochemistry study was performed to verify the
      survival of the transplanted cells. RESULTS: The putative RPE cells derived from
      hESC showed characteristics of the human RPE cells morphologically and expressed
      molecular markers and associated with RPE fate. Grafted RPE cells were found to
      survive in the subretinal space up to 4 weeks after transplantation, and the
      expression of RPE markers was confirmed with immunohistochemistry. CONCLUSION:
      Transplanted RPE cells derived from hESC in the defined culture condition
      successfully survived and migrated within subretinal space of rat retinal
      degeneration model. These results support the feasibility of the hESC derived RPE
      cells for cell-based therapies for retinal degenerative disease.

PMID- 22384446
TI  - Serum anti-Mullerian hormone is a better predictor of ovarian response than FSH
      and age in IVF patients with endometriosis.
AB  - OBJECTIVE: To evaluate the ability of serum anti-Mullerian hormone (AMH), FSH,
      and age to clinically predict ovarian response to controlled ovarian
      hyperstimulation (COH) in IVF patients with endometriosis. METHODS: We evaluated
      91 COH cycles, including 43 cycles with endometriosis (group I) and 48 cycles
      with male factor infertility (group II) from January to December, 2010. Patients
      were classified into study groups based on their surgical history of
      endometriosis-group Ia (without surgical history, n=16), group Ib (with a
      surgical history, n=27). RESULTS: The mean age was not significantly different
      between group I and group II. However, AMH and FSH were significantly different
      between group I and group II (1.9+/-1.9 ng/mL vs. 4.1+/-2.9 ng/mL, p<0.01; 13.1+/
      7.2 mIU/mL vs. 8.6+/-3.3 mIU/mL, p<0.01). Furthermore, the number of retrieved
      oocytes and the number of matured oocytes were significantly lower in group I
      than in group II. In group II, AMH and FSH as well as age were significant
      predictors of retrieved oocytes on univariate analysis. Only the serum AMH level
      was a significant predictor of poor ovarian response in women with endometriosis.
      CONCLUSION: Serum AMH may be a better predictor of the ovarian response of COH in
      patients with endometriosis than basal FSH or age. AMH level can be considered a
      useful clinical predictor of poor ovarian response in endometriosis patients.

PMID- 22384447
TI  - GnRH antagonist multiple dose protocol with oral contraceptive pill pretreatment
      in poor responders undergoing IVF/ICSI.
AB  - OBJECTIVE: To investigate the effectiveness of GnRH antagonist multiple-dose
      protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders
      undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment
      and GnRH agonist low-dose long protocol (LP). METHODS: A total of 120 poor
      responders were randomized into three groups according to controlled ovarian
      stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1),
      GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low
      dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were
      pretreated with OCP for 21days in the cycle preceding COS, and ovarian
      stimulation using recombinant human FSH (rhFSH) was started 5 days after
      discontinuation of OCP. RESULTS: There were no differences in patients'
      characteristics among three groups. Total dose and days of rhFSH used for COS
      were significantly higher in group 3 than in group 1 or 2. The numbers of mature
      oocytes, fertilized oocytes and grade I, II embryos were significantly lower in
      group 2 than in group 1 or 3. There were no significant differences in the
      clinical pregnancy rate and implantation rate among three groups. CONCLUSION:
      GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH
      agonist low-dose LP in poor responders and can benefit the poor responders by
      reducing the amount and duration of FSH required for follicular maturation.

PMID- 22384448
TI  - Oocyte maturity in repeated ovarian stimulation.
AB  - OBJECTIVE: During stimulated IVF cycles, up to 15% of oocytes are recovered as
      immature. The purpose of this study was to investigate the trend of oocyte
      maturity in repeated ovarian stimulation for IVF. METHODS: One hundred forty
      eight patients were selected who underwent two consecutive IVF cycles using same
      stimulation protocol during 2008 to 2010. Ovarian stimulation was performed with
      FSH and human menopausal gonadotropin and flexible GnRH antagonist protocol in
      both cycles. Oocyte maturity was assessed according to presence of germinal
      vesicle (GV) and the first polar body. Immature oocyte was defined as GV stage or
      metaphase I oocyte (GV breakdown with no visible polar body) and cultured up to
      48 hours. If matured, they were fertilized with ICSI. RESULTS: Percentages of
      immature oocytes were 30.8% and 32.9% (p=0.466) and IVM rates of immature oocytes
      were 36.2% and 25.7% (p=0.077), respectively. A significant correlation was noted
      between percentage of immature oocytes in the two cycles (R=0.178, p=0.03). Women
      with >40% immaturity in both cycles (n=21) showed lower fertilization rate of in
      vivo matured oocytes (56.4% vs. 72.0%, p=0.005) and lower pregnancy rate (19.0%
      vs. 27.1%, p=0.454) after the second cycle when compared with women with <40%
      immaturity (n=70). In both groups, female age, number of total retrieved oocyte
      and embryos transferred were similar. CONCLUSION: In repeated ovarian stimulation
      cycles for IVF, the immature oocyte tended to be retrieved repetitively in
      consecutive IVF cycles.

PMID- 22384449
TI  - Duplication of intrachromosomal insertion segments 4q32->q35 confirmed by
      comparative genomic hybridization and fluorescent in situ hybridization.
AB  - A 35-year-old man with infertility was referred for chromosomal analysis. In
      routine cytogenetic analysis, the patient was seen to have additional material of
      unknown origin on the terminal region of the short arm of chromosome 4. To
      determine the origin of the unknown material, we carried out high-resolution
      banding, comparative genomic hybridization (CGH), and FISH. CGH showed a gain of
      signal on the region of 4q32->q35. FISH using whole chromosome painting and
      subtelomeric region probes for chromosome 4 confirmed the aberrant chromosome as
      an intrachromosomal insertion duplication of 4q32->q35. Duplication often leads
      to some phenotypic abnormalities; however, our patient showed an almost normal
      phenotype except for congenital dysfunction in spermatogenesis.

PMID- 22384450
TI  - Fidaxomicin, a new treatment for Clostridium difficile infections.
AB  - Clostridium difficile is currently the most important cause of infectious
      diarrhea in the United States. Fidaxomicin, a macrolide antibiotic, was recently
      approved for treatment of C. difficile infections (CDIs). In vitro studies
      demonstrate that fidaxomicin has a narrow spectrum of activity against C.
      difficile with minimal effect on the gut flora. Clinical trials indicate that
      fidaxomicin is as effective as vancomycin for treatment of CDI with fewer
      recurrences. Additionally, fidaxomicin has minimal systemic absorption with few
      adverse side effects. Thus, fidaxomicin is an attractive new alternative for
      treatment of CDI.

PMID- 22384451
TI  - Vemurafenib: the road to personalized medicine in melanoma.
AB  - Advanced melanoma has a poor prognosis due to its resistance to traditional
      chemotherapeutics, leading to the search for alternative treatment approaches.
      With the finding that approximately 50% of melanomas harbor an activating
      mutation in the serine/threonine-protein kinase B-raf gene (BRAF), inhibition of
      mutated B-raf represented an attractive and innovative focus for the development
      of novel targeted therapy potentially benefiting a large proportion of melanoma
      patients. Impressive response rates with an overall survival benefit in addition
      to minimal treatment-related toxicity in phase I-III clinical studies led to the
      FDA's approval of vemurafenib for patients with locally advanced/unresectable or
      metastatic BRAFV600E-mutated malignant melanoma in August 2011. While the
      majority of patients with BRAF-mutated disease show favorable treatment responses
      shortly after initiation of vemurafenib therapy, the median progression-free
      survival is 6 months, making the search for resistance mechanisms a high
      priority. While vemurafenib represents an excellent model for successful targeted
      anticancer therapy, long-term safety data are needed and rational combination
      with other agents will be critical to prevent or circumvent the development of
      resistance.

PMID- 22384452
TI  - New formulations of fentanyl for acute pain management.
AB  - Intravenous fentanyl citrate has stood the test of time as a valuable formulation
      for pain management. The desirable physicochemical properties of fentanyl have
      allowed the development of several alternative formulations for delivery using
      less invasive routes, for example, transmucosal (intranasal, oral buccal and oral
      sublingual) and transdermal. These new formulations have been applied to clinical
      settings in which rapid onset of analgesia is desired, using convenient but
      noninvasive methods. Recent commercialization of various formulations has been
      driven largely by the needs of cancer patients, for whom severe but self-limiting
      "breakthrough" pain is less suitably treated by parenteral or oral routes of
      opioid administration. However, these formulations are also used for acute
      analgesia in prehospital and in-hospital emergency department care, and for
      pediatric acute pain management. Finally, they are increasingly used by patients
      with chronic pain of nonmalignant origin, although there is considerable debate
      about their merit in this group. We searched the databases MEDLINE, PubMed,
      EMBASE, CINAHL and Cochrane up to October 2011, using search terms "fentanyl AND
      nasal; intranasal; transmucosal; buccal; sublingual; oral; inhaled; inhalation;
      transdermal". The characteristics of several formulations of fentanyl are
      reviewed, detailing their pharmacokinetics, pharmacodynamics and clinical
      experience with their use for acute pain management.

PMID- 22384453
TI  - Current and future treatment of pulmonary hypertension.
AB  - Pulmonary hypertension is a disorder characterized by an increase in mean
      pulmonary arterial pressure (mPAP > 25 mmHg), which is responsible for the
      transport of blood from the heart to the lungs. Increased pressure leads to
      decreased flow of blood through the lungs and decreased oxygen deliverance
      throughout the body. The disorder causes right ventricular hypertrophy and can
      quickly lead to death, especially with the severe forms of pulmonary
      hypertension. Symptoms include fatigue, shortness of breath, dizziness and
      peripheral edema in the lower extremities. Symptoms are usually delayed in
      appearance and progress slowly, which leads to a late diagnosis and often a poor
      prognosis. Despite large advances in the last 10 years, there is still about a
      15% annual mortality for diagnosed patients. Despite the number of medications
      available, there are still no cures for this fatal disease. Current therapies
      include endothelin receptor antagonists, prostacyclin agonists and cGMP-specific
      3',5'-cyclic phosphodiesterase (PDE5) inhibitors or combinations. Recent
      strategies have shown promise in animal models to prevent the onset of pulmonary
      hypertension when it is induced. However, few of them show a sustained benefit in
      clinical trials. Strategies for the cure of this debilitating disease should be
      the focus of future research.

PMID- 22384454
TI  - Fecal lactoferrin as a noninvasive biomarker in inflammatory bowel diseases.
AB  - The diagnosis and management of inflammatory bowel diseases (IBD), i.e., Crohn's
      disease and ulcerative colitis, still present a number of challenges. The fecal
      biomarker lactoferrin has been shown to be useful in the diagnosis and management
      of these diseases. This review includes a discussion of the current literature on
      lactoferrin as a biomarker of intestinal disease, detection of disease activity
      in IBD, comparison of lactoferrin to endoscopy and histology, lactoferrin
      measurement in pediatric IBD and lactoferrin as a biomarker for monitoring
      medical treatment in IBD.

PMID- 22384455
TI  - Report from the 29th World Congress of Endourology and SWL (November 30-December
      3, 2011 - Kyoto, Japan).
AB  - Kyoto is a city of surprises: from the most beautiful castles and temples known
      far and wide across the world, to the humblest temples, as beautiful as those
      appearing in all tourist guides, just hidden away in small lanes among busy
      traffic of bicycles and pedestrians shopping in markets or attending to their
      daily business. Add the innumerable tourists busily exploring the city's
      attractions, although this was not the reason for visiting Kyoto, which was the
      site of this year's World Congress of Endourology and SWL. Nevertheless, maybe as
      a compensation, the meeting was held in Kokusaikaikan, literally the
      International Conference Centre, which is a modern facility in the city
      outskirts, actually adjoining the Takaragaike park, with a beautiful lake and the
      mountains, brightly led by the trees' red leaves, just visible through the main
      hall windows.

PMID- 22384456
TI  - Avanafil for the treatment of erectile dysfunction.
AB  - Erectile dysfunction is a prevalent condition afflicting millions of men
      worldwide and can have disastrous effects on a couple's quality of life. With the
      understanding of the physiology of erections and the discovery of cGMP-specific
      3',5'-cyclic phosphodiesterase (PDE5) inhibitors, therapy for erectile
      dysfunction was revolutionized, and this class of medication became the first
      line treatment option for this widespread condition. Despite the ease of use,
      efficacy and tolerability of the available PDE5 inhibitors, many men discontinue
      their use, usually related to lack of efficacy or development of adverse events.
      As such, research into the development of other medications within this drug
      class is extensive. Avanafil is a novel PDE5 inhibitor with favorable
      pharmacokinetic and pharmacodynamic profiles with good tolerability and limited
      adverse events. It was recently approved and launched in Korea, and is currently
      under review by the U.S. Food and Drug Administration. Its efficacy and purported
      role in the treatment for erectile dysfunction are reviewed here.

PMID- 22384457
TI  - Dutasteride/tamsulosin fixed-dose combination for the treatment of benign
      prostatic enlargement.
AB  - Fixed-dose dutasteride/tamsulosin is a combination therapy for lower urinary
      tract symptoms secondary to benign prostatic enlargement (LUTS/BPE), which is
      composed of two active ingredients, tamsulosin and dutasteride. Tamsulosin is an
      alpha-adrenoceptor blocker that is relatively selective for the alpha(1A)
      adrenoceptor subtype within the prostatic smooth muscles. The inhibition of
      alpha(1A)-adrenoceptors results in smooth muscle relaxation. Dutasteride is an
      inhibitor of 5alpha-reductase, an enzyme that is responsible for the conversion
      of testosterone to its active form dihydrotestosterone. This occurs in the
      prostate, liver and skin. 5alpha-Reductase results in the shrinkage of the
      prostatic epithelium and reduction in the size of the prostate. No clinical
      studies have been performed on the fixed-dose dutasteride/tamsulosin combination,
      although several clinical trials have been conducted on the combination therapy
      of 5alpha-reductase and alpha-adrenoceptor blockers for LUTS/BPE. The CombAT
      study is a multicenter, randomized, double-blind trial in men with a clinical
      diagnosis of LUTS/BPE that is comparing tamsulosin or dutasteride as a
      monotherapy to tamsulosin and dutasteride as combination therapy (as separate
      tablets). The combination therapy was associated with significant improvements in
      the symptom score compared to tamsulosin or dutasteride as monotherapy. It is
      therefore logical to combine the two medications into one tablet.

PMID- 22384458
TI  - Mirabegron for the treatment of overactive bladder.
AB  - Overactive bladder (OAB) syndrome is defined as urinary urgency, usually
      accompanied by frequency and nocturia, with or without urge urinary incontinence,
      in the absence of urinary tract infection or other obvious pathology. Mirabegron
      (YM-178, Betanis(r)) is a novel, once-daily, orally active, first-in-class
      selective beta(3)-adrenoceptor agonist that improves symptoms associated with OAB
      by enhancing storage function and relaxing the urinary bladder. Mirabegron has
      been approved in Japan for the indication of urgency, urinary frequency and urge
      urinary incontinence associated with OAB, and was recently submitted for approval
      to U.S. and European authorities for the same indication. In phase III clinical
      trials performed in Europe, the U.S. and Australia, mirabegron at doses of 50 or
      100 mg for 12 weeks significantly decreased the mean number of incontinence
      episodes and micturition episodes per 24 hours, and was safe and well tolerated.
      Mirabegron may be an alternative in patients with OAB who are poor responders to
      antimuscarinic agents or intolerant of their adverse effects.

PMID- 22384459
TI  - The year's new drugs & biologics, 2011.
AB  - 2011 was a good year in many respects for the pharmaceutical industry, especially
      regarding the approval and launch of several important new products. The FDA
      reported a record high rate of approvals during FY2011 (October 1, 2010-September
      30, 2011), reflecting the agency's commitment to maintaining "a state-of-the-art
      drug approval process that brings important drugs to market quickly and
      efficiently" (1). While not all of the new drugs and biologics listed in FDA's
      fiscal year summary meet the criteria for inclusion in this article, most of them
      do, and hence are reviewed in the following pages. Also covered in this year's
      expanded article are new approvals and new launches in other global markets, line
      extensions and other developments of interest to the industry: generic drug
      approvals, product withdrawals and discontinuations, new developments in the area
      of orphan drugs and diseases, and more.

PMID- 22384460
TI  - A report from the American Heart Association Scientific Sessions 2011 (November
      12-16, 2011, Orlando, Florida, USA).
AB  - Diet and lifestyle have a direct impact on cardiovascular health and may help
      improve the condition in many patients suffering from or at risk for cardiac
      diseases, and remote and in-person behavioral interventions were shown to prompt
      weight loss in obese individuals (Appel, L.J., Late-Breaking Clinical Trial
      presentation), thus helping reduce the cardiovascular risk. In that regard, and
      as an example, kiwifruit was noted to lower 24-hour blood pressure (Svendsen, M.
      et al., Abst 16175), whereas alcoholic beverages (at least red wine and vodka)
      were reported to improve the cardiovascular risk by increasing collateral
      perfusion and, in the case of red wine, to enhance antioxidant cardioprotection
      (Chu, L.M. et al., Abst 16380), drug therapy is required for treating a vast
      array of medical conditions affecting the heart and vessels, as well as many
      cardiovascular risk factors very common in the general population. These issues
      were widely discussed in the context of new findings with improved therapies
      tested in clinical or preclinical studies during AHA's scientific sessions in
      Orlando, as summarized in the following report.

PMID- 22384462
TI  - [Not Available].

PMID- 22384461
TI  - [Not Available].

PMID- 22384463
TI  - Guidelines for controlled trials of drugs in migraine: third edition. A guide for
      investigators.

PMID- 22384464
TI  - [Malaria mosquito resistant against insecticides].

PMID- 22384465
TI  - Christian Gerhard Leopold: fascinating history of a productive obstetrician
      gynecologist.

PMID- 22384466
TI  - [Diagnostics and treatment of spontaneous nasal CSF leak in patients with
      metabolic syndrome].

PMID- 22384467
TI  - Keeping patients in care:  a critical component in controlling HIV.

PMID- 22384468
TI  - Documenting mental health for disability claims.

PMID- 22384469
TI  - A practical new approach to medication adherence in HIV.

PMID- 22384470
TI  - Eradicating stigma through bilingual and multicultural education.

PMID- 22384471
TI  - Refeeding syndrome:  an old problem with new challenges.

PMID- 22384472
TI  - Should longterm stable patients have biannual monitoring?

PMID- 22384473
TI  - Treatment.  Kidney transplants available for HIV-positive.

PMID- 22384474
TI  - Research.  Health classes must remove focus on tests to improve safe sex habits.

PMID- 22384475
TI  - Research. HIV, syphilis rates quickly rising among New York City MSM.

PMID- 22384476
TI  - African immigrants and sex.

PMID- 22384477
TI  - HIV-positive children not receiving adequate treatment.

PMID- 22384478
TI  - Prisons. Inmate's privacy rights not violated by presence of COs.

PMID- 22384479
TI  - SSI.  Court affirmed denial of benefits to man with HIV, anxiety.

PMID- 22384480
TI  - Insurance. Benefits correctly terminated for man no longer disabled.

PMID- 22384481
TI  - Crimnal.  Court affirms conviction for HIV-positive man who bit officer.

PMID- 22384482
TI  - [Concerning the    public/private dichotomy: the family and women in three French
      authors of the    early 19th century].

PMID- 22384483
TI  - Making links across the lifespan in neurology.

PMID- 22384484
TI  - Growing up with cerebral palsy: contemporary challenges of healthcare transition.
AB  - Cerebral palsy is traditionally known as a major cause of chronic disability in
      childhood. With advances in neonatal care and improved survival, the majority of
      adolescents with cerebral palsy require ongoing services into adulthood. This
      paper highlights some of the challenges in their transition from pediatric to
      adult healthcare and proposes key elements to ensure a smooth transition process.

PMID- 22384485
TI  - Kudos to our reviewers (along with a few suggestions).

PMID- 22384486
TI  - Untangling the vascular web from Alzheimer disease and oxidative stress.

PMID- 22384487
TI  - Biomarkers of oxidative stress in vascular dementia patients.
AB  - OBJECTIVE: Little is known about the role of oxidative stress in the pathogenesis
      of vascular dementia (VaD). The aim of this study was to investigate the
      biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine
      (8-OHdG), 8-isoprostaglandin F(2a) (8-isoPGF(2a)) and nitrotyrosine (NT) levels,
      in a group of well characterized VaD patients and in two control groups of
      Vascular Not Demented (VaND) patients and health y subjects. METHODS: Ninety-six
      subjects from the Tianjin municipality in China were recruited. Forty-six
      patients were in the VaD group, 24 patients with VaND and 26 persons with no
      signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8
      isoPGF(2a) was performed using enzyme-linked immunosorbent assay (ELISA), and
      urinary NT levels were measured by chemiluminescence detection. RESULTS:
      Significantly higher urinary 8-OHdG levels were detected in VaD patients compared
      to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF(2a)
      levels were significantly lower in VaD patients compared with two control groups.
      For NT levels, no statistically significant differences were observed among the
      three groups. CONCLUSION: Increased urinary 8-OHdG level was a potential marker
      of oxidative stress in VaD patients. Furthermore, it is also important to take
      into account potential confounders in order to improve the identification of
      changes in the status of oxidative stress as related to VaD.

PMID- 22384488
TI  - In this issue of Recent Patents on CNS Drug Discovery, focus is laid upon the
      potential development of new therapeutic drugs for neurological and affective
      disorders through targeting the endocannabinoid system. Introduction.

PMID- 22384489
TI  - [National Days of Laboratory Medicine in Russia--2011. Scientific and Practical
      Conference "Providing Access to Modern Clinical Laboratory Research--Analytical
      Capabilities, Clinical Needs, and Organizational and Economic Conditions".
      Abstracts. October 4-6, 2011, Moscow].

PMID- 22384490
TI  - Inflammatory demyelinating brain lesions heralding primary CNS lymphoma.
AB  - Brain biopsy plays a crucial role in the exploration of suspect white matter
      lesions in the differential diagnosis of primary central nervous system lymphoma
      (PCNSL) and inflammatory demyelination. We present the case of a previously
      healthy, immunocompetent woman, aged fifty-nine, who developed a histologically
      confirmed demyelinating white matter lesion months prior to the manifestation of
      a PCNSL. Similar cases of "sentinel lesions" preceding a PCNSL have been
      reported. In a literature review, we compared the diagnostic features that may be
      useful to differentiate a PCNSL from inflammatory demyelinating disease in older
      age. We conclude that the occurrence of large, contrast-enhancing cerebral
      lesions in older patients with a relapsing-remitting disease course and steroid
      resistant vision disorders should lead to the consideration of a PCNSL.

PMID- 22384491
TI  - Brain-machine interfaces for motor control: a guide for neuroscience clinicians.
AB  - With the growing interdependence between medicine and technology, the prospect of
      connecting machines to the human brain is rapidly being realized. The field of
      neuroprosthetics is transitioning from the proof of concept stage to the
      development of advanced clinical treatments. In one area of brain-machine
      interfaces (BMIs) related to the motor system, also termed 'motor
      neuroprosthetics', research successes with implanted microelectrodes in animals
      have demonstrated immense potential for restoring motor deficits. Early human
      trials have also begun, with some success but also highlighting several technical
      challenges. Here we review the concepts and anatomy underlying motor BMI designs,
      review their early use in clinical applications, and offer a framework to
      evaluate these technologies in order to predict their eventual clinical utility.
      Ultimately, we hope to help neuroscience clinicians understand and participate in
      this burgeoning field.

PMID- 22384492
TI  - Psychological interventions for headache in children and adolescents.
AB  - Headache in children and adolescents represents a number of complex and
      multifaceted pain syndromes that can benefit from psychological intervention.
      There is good evidence for the efficacy of cognitive behavioral therapy,
      relaxation training, and biofeedback. The choice of intervention is influenced by
      patients' age, sex, family and cultural background, as well as the nature of
      stressors and comorbid psychiatric symptoms. Management must always be family
      centered. Psychological treatments are essential elements of the
      multidisciplinary, biopsychosocial management of primary headache disorders,
      particularly for those with frequent or chronic headache, a high level of
      headache-related disability, medication overuse, or comorbid psychiatric
      symptoms. Future studies of efficacy and effectiveness of psychological treatment
      should use the International Headache Society's definition and classification of
      headache disorders, and stratify results by headache type, associated conditions,
      and treatment modality.

PMID- 22384493
TI  - A Canadian paradox: Tommy Douglas and eugenics.
AB  - Tommy Douglas is an icon of Canadian 20th Century political history and is
      considered by many as the "Father" of Medicare, a key component of our national
      identity. Throughout his career, he was associated at both the provincial and
      federal levels with progressive causes concerning disadvantaged populations. In
      his sociology Master's thesis written in the early 1930's, Douglas endorsed
      eugenic oriented solutions such as segregation and sterilization to address what
      was perceived to be an endemic and biologically determined problem. At first
      glance, this endorsement of eugenics appears to be paradoxical, but careful
      analysis revealed that this paradox has multiple roots in religion, political
      belief, historical exposure and our own desire to view our collective history in
      a favourable light.

PMID- 22384494
TI  - Essential role of excessive tryptophan and its neurometabolites in fatigue.
AB  - PURPOSE: Serotonin, a neurotransmitter synthesized from tryptophan, has been
      proposed to play a key role in central fatigue. In this study, we examined
      whether tryptophan itself and/or its two metabolites, kyneurenic acid (KYNA) and
      quinolinic acid (QUIN), are involved in central fatigue. MATERIALS AND METHODS:
      Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase
      analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a
      Morris water maze test. Microdialysis was used to collect samples for measurement
      of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic
      acid (5-HIAA) and to infuse test agents. To examine the kinetics of release,
      synaptosomes in the striatum were prepared in vitro to measure intra- and
      extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA. RESULTS: The
      concentration of tryptophan secreted into the extracellular space of the striatum
      was higher during fatigue only, and quickly returned to basal levels with
      recovery from fatigue. Running time to exhaustion was reduced by activation of
      tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a
      higher extracellular level of striatum tryptophan than SDR. Impaired memory
      performance in a water maze task after tryptophan treatment was attributable to
      high levels of KYNA and QUIN in the hippocampus acting synergistically on N
      methyl-D-aspartic acid receptors. When branched-chain amino acids were
      administered, tryptophan transport to the extracellular space of the striatum was
      drastically inhibited. CONCLUSION: Our findings demonstrate that the increase in
      fatigue which occurs because of excessively elevated brain tryptophan can be
      further amplified by the use of synthetic KYNA and QUIN.

PMID- 22384495
TI  - Predictors of survival in a Huntington's disease population from southern Italy.
AB  - BACKGROUND: The primary aim of the present study was to determine the survival
      rates and identify predictors of disease duration in a cohort of Huntington's
      disease (HD) patients from Southern Italy. METHODS: All medical records of HD
      patients followed between 1977 and 2008 at the Department of Neurological
      Sciences of Federico II University in Naples were retrospectively reviewed and
      135 patients were enrolled in the analysis. At the time of data collection, 41
      patients were deceased (19 males and 22 females) with a mean +/- SD age at death
      of 56.6 +/- 14.9 years (range 18-83). RESULTS: The median survival time was 20
      years (95% CI: 18.3-21.7). Cox regression analysis showed that the number of CAG
      in the expanded allele (HR 1.09 for 1 point triplet increase, p=0.002) and age of
      onset (HR 1.05 for 1 point year increase, p=0.002) were independent and
      significant predictors of lower survival rates. CONCLUSIONS: We believe that
      these findings are important for a better understanding of the natural history of
      the disease and may be relevant in designing future therapeutic trials.

PMID- 22384496
TI  - Dopamine alters tactile perception in Parkinson's disease.
AB  - BACKGROUND: Abnormal somatosensory processing may contribute to motor impairments
      observed in Parkinson's disease (PD). Dopaminergic medications have been shown to
      alter somatosensory processing such that tactile perception is improved. In PD,
      it remains unclear whether the temporal sequencing of tactile stimuli is altered
      and if dopaminergic medications alter this perception. METHODS: Somatosensory
      tactile perception was investigated using temporal order judgment in patients
      with Parkinson's disease on and off dopaminergic medications and in aged-matched
      healthy controls. Measures of temporal order judgment were acquired using
      computer controlled stimulation to digits 2 and 3 on the right hand and subjects
      were required to determine which stimuli occurred first. Two experimental tasks
      were compared, temporal order judgment without and with synchronization whereby
      digits 2 and 3 were vibrated synchronously in advance of the temporal order
      judgment sequence of stimuli. RESULTS: Temporal order judgment in PD patients of
      and on medications were similar to controls. Temporal order judgment preceded by
      synchronous vibration impaired tactical acuity in controls and in PD patients off
      medications to similar degrees, but this perceptual impairment by synchronous
      vibration was not present in PD patients on medications. CONCLUSIONS: These
      findings suggest that dopamine in PD reduces cortico-cortical connectivity with
      SI and this leads to changes in tactical sensitivity.

PMID- 22384497
TI  - Cytokine gene polymorphisms and Parkinson's disease: a meta-analysis.
AB  - BACKGROUND: Cytokines, which are involved in immunological responses, play and
      important role in the development and progression of Parkinson's disease (PD).
      The functional polymorphisms identified in cytokine genes are thought to
      influence PD risk. However the findings of studies investigating the association
      between cytokine gene polymorphisms and PD risk are still controversial.
      Therefore, we conducted a meta-analysis, in order to investigate the potential
      associations between cytokine gene polymorphisms and PD. METHODS: Studies of PD
      and cytokine polymorphisms were identified by searches of PubMed and PDGene.
      Pooled analyses were performed to assess the association between cytokine gene
      polymorphisms and PD. RESULTS: Our results indicated a positive association of
      TNFalpha -1031 CC genotype in overall analysis(CC vs. TT: OR=3.146; 95%CI: 1.631
      6.070, p=0.008; CC vs. CT+TT: OR=3.187: 95%CI: 1.657-6.128,p=0.008), and an Asian
      subgroup, C variant(OR=1.328; 95%CI: 1.053-1.675, p=0.034) also conveyed an
      increased PD risk as well as CC genotype ( CC vs. TT: OR=3.207; 95%CI: 1.614
      6.373, p=0.004; CC vs. CT+TT: OR=3.238; 95%CI: 1.636-6.410, p=0.004). A decreased
      risk for PD was associated with IL-6-174C allele (OR=0.761; 95%CI: 0.641-0.903,
      p=0.008) and IL-1RA VNTR 2 allele(OR=0.641; 95%CI: 0.456-0.826 p=0.004). For the
      polymorphisms of IL-1beta C[-511]T, IL-1alpha C[-889]T , TNFalpha G[-308]A, and
      IL-10 G[-1082]A no significant association was found between the gene
      polymorphisms and PD risk. CONCLUSIONS: Our meta-analysis suggested that gene
      polymorphisms of TNFalpha -1031, IL-6-174 and IL-1RA VNTR may be associated with
      PD risk. However, more large well-designed studies will be necessary to validate
      our findings.

PMID- 22384498
TI  - Serum CRP concentrations and severity of ischemic stroke subtypes.
AB  - OBJECTIVE: The aim of this retrospective study was to investigate if elevated C
      reactive protein (CRP) was related to the stroke severity, and to analyze its
      different distribution in stroke subtypes. METHODS: 316 patients with acute
      ischemic stroke (AIS) were enrolled and had CRP determinations; they were
      dichotomized as<7 or >=7mg/L according to the previous report. 128 patients with
      transient ischemic attack who also had CRP measurements were selected as
      controls. A possible level-risk relationship between elevated CRP and NIHSS,
      which considered relatively severe illness as a value>=8, was studied within the
      AIS group. RESULTS: CRP was elevated in 21% of the AIS compared to 4% in the
      control group (p = 0.000). Within the AIS group, patients with CRP levels >=7mg/L
      had a significantly increased risk of severe stroke (OR 3.33, 95% CI 1.84-6.00, p
      =0.00). In subtype stroke, the highest rate of elevated CRP and NIHSS were in
      those with cardioembolic stroke (CE) using TOAST classification, total anterior
      circulation infarction (TACI) of OCSP classification and large volume infarction
      (LVI) of Adams classification; the odds ratio(OR) between elevated CRP and NIHSS
      was 6.14 (95% CI 1.43-26.44) in CE, 1.714 (95% CI 1.30-2.26) in TACI, 2.32 (95%
      CI 1.08-4.99) in LVI, and the p value were all below 0.05. CONCLUSION: Elevated
      CRP level can reflect the severity of AIS, which was association with stroke
      subtype.

PMID- 22384499
TI  - Sex differences in adult cerebral venous sinus thrombosis: a 10-year experience.
AB  - BACKGROUND: Sex differences in the risk factors, presentation and outcome of
      cerebral venous sinus thrombosis (CVST) are poorly defined, despite a discrepant
      prevalence between males and females. The proportion of patients on hormonal
      therapy who develop CVST varies widely. We describe the clinical features, risk
      factors and outcome by sex and by hormone-related risk factors among a large
      cohort of patients. METHODS: We reviewed records of 108 consecutive patients with
      CVST at a tertiary hospital in Calgary between 1999 and 2009. Descriptive
      statistics were used for between group comparisons (men, women with hormone
      related risk factors and women without hormone-related risk factors). RESULTS:
      Females made up 62% of patients, half of whom were on systemic hormonal therapy.
      Men and women without hormonal risk factors were older at onset. Oral
      contraceptive use was the major risk factor in women (45%) while concurrent
      mastoiditis was the most common predisposing factor in men (27%). Complications
      were frequent and overall mortality was 6%. Persisting deficits at discharge were
      more common in men (54% vs. 35% and 32%, p=0.036). There was a trend for women
      with hormone-related risk factors to have less residual focal neurologic deficit
      than the other groups (5% vs. 15% and 17%, p=0.051). CONCLUSIONS: There are
      differences between sexes in the presentation, risk factors and outcome of
      patients with CVST.

PMID- 22384500
TI  - Ethical challenges with awake craniotomy for tumor.
AB  - BACKGROUND: Awake brain surgery is useful for the treatment of a number of
      conditions such as epilepsy and brain tumor, as well as in functional
      neurosurgery. Several studies have been published regarding clinical results and
      outcomes of patients who have undergone awake craniotomy but few have dealt with
      related ethical issues. OBJECTIVE: The authors undertake to explore broadly the
      ethical issues surrounding awake brain surgery for tumor resection to encourage
      further consideration and discussion. METHODS: Based on a review of the
      literature related to awake craniotomy and in part from the personal experience
      of the senior author, we conducted an assessment of the ethical issues associated
      with awake brain tumor surgery. RESULTS: The major ethical issues identified
      relate to: (1) lack of data; (2) utilization; (3) conflict of interest; (4)
      informed consent; (5) surgical innovation; and (6) surgical training. CONCLUSION:
      The authors respectfully suggest that the selection of patients for awake
      craniotomy needs to be monitored according to more consistent, objective
      standards in order to avoid conflicts of interest and potential harm to patients.

PMID- 22384501
TI  - Improving the neurological exam skills of medical students.
AB  - OBJECTIVE: Determine if distributed practice of of neurological exam (NE) skills
      in first year medical school produces sustained improvements in the skills of
      second year students. METHODS: A prospective, controlled, non-blinded study
      conducted at McGill University (class size = 180 students). Expanded teaching of
      muscle stretch reflexes was provided to first year medical students. A structured
      examination of muscle stretch reflexes (max score = 100) was administered in
      second year medical school after a required two week rotation in Neurology.
      Results for class A (received the intervention in first year) were compared to
      the results for the preceding class B (had not received the intervention).
      RESULTS: 77 of 177 (44%) eligible in class A and 69 of 166 (42%) eligible
      students in class B participated. Results were analyzed separately for each of
      the two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention)
      and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for
      class A and 83.8 (11.7) for class B for the second examiner. Results were
      statistically significant (Mann-Whitney test z = 5.27, p<0.0001 first examiner
      and z = 2.67, p<0.0038 second examiner). CONCLUSIONS: Distributed practice of
      muscle stretch reflexes during first year medical school results in improved
      performance by second year medical students after their mandatory clinical
      rotation in neurology, even when examined up to 14 months after the intervention.
      This finding has implications for the teaching of the NE.

PMID- 22384502
TI  - Epilepsy and crossed cerebellar diaschisis with persistent cerebellar syndrome.

PMID- 22384503
TI  - Corticotroph pituitary stone.

PMID- 22384504
TI  - CYP7B1 mutations in French-Canadian hereditary spastic paraplegia subjects.

PMID- 22384505
TI  - Rosette-forming glioneuronal tumour of the 4th ventricle in a NF1 patient.

PMID- 22384506
TI  - Slow alpha variant: a report of a 3 for 1 ratio subharmonic.

PMID- 22384507
TI  - Transient radiographic early enhancement after radiotherapy for meningioma.

PMID- 22384508
TI  - Enhancing acute ischemic stroke interpretation with online aspects training.

PMID- 22384509
TI  - Repeated systemic thrombolysis after early recurrent stroke: always hazardous?

PMID- 22384510
TI  - Intracranial non-occlusive thrombus and multiple strokes in giant cell arteritis.

PMID- 22384511
TI  - Plaque-type blue nevus with meningeal melanocytomas.

PMID- 22384512
TI  - Fatal cerebellar hemorrhage following Australian brown snake envenomation.

PMID- 22384513
TI  - TACH leukodystrophy: locus refinement to chromosome 10q22.3-23.1.

PMID- 22384514
TI  - Biochemia Medica indexed in Medline.
AB  - Biochemia Medica has been approved for inclusion in PubMed/Medline bibliographic
      database, from the first issue published in 2011 year. We believe that this
      outstanding achievement comes as acknowledgment for many past efforts and some
      recent developments of the journal Editorial Board, such as recent launch of a
      new web page, online manuscript submission system and the implementation of the
      revised policy on the Statement of Conflict of Interest. We will continue our
      committed work to maintain the timeliness of publication, publication ethics and
      research integrity, and further improve the quality of content as well as the
      quality of the editorial work and production of the Journal. We sincerely hope
      that inclusion of our Journal in PubMed will enable us to increase its
      international visibility and the number of high-quality submissions.

PMID- 22384515
TI  - Biomedical research platforms and their influence on article submissions and
      journal rankings: an update.
AB  - After being indexed in 2006 in EMBASE/Excerpta Medica and Scopus, and later in
      Science Citation Index Expanded and Journal Citation Reports/ Science Edition
      citation databases, Biochemia Medica launched a new web page and online
      manuscript submission system in 2010, and celebrated its first Impact Factor in
      the same year. Now, starting from the end of the 2011, the journal will also be
      indexed in PubMed/Medline, and this will contribute to increase the journal's
      exposure and accessibility worldwide. This is an important breakthrough, which is
      expected to further increase the popularity of the journal, as well as the
      submission rate and citations. Although several tools are currently available as
      Web resources to retrieve scientific articles, whose functioning and basic
      criteria are thought to be rather similar, the functionality, coverage, notoriety
      and prominence may differ widely. The recent indexing of Biochemia Medica in
      PubMed/Medline has thereby given us the opportunity to provide a timely update on
      biomedical research platforms, their relationship with article submissions and
      journal rankings.

PMID- 22384516
TI  - Practical recommendations for statistical analysis and data presentation in
      Biochemia Medica journal.
AB  - The aim of this article is to highlight practical recommendations based on our
      experience as reviewers and journal editors and refer to some most common
      mistakes in manuscripts submitted to Biochemia Medica. One of the most important
      parts of the article is the Abstract. Authors quite often forget that Abstract is
      sometimes the first (and only) part of the article read by the readers. The
      article Abstract must therefore be comprehensive and provide key results of your
      work. Problematic part of the article, also often neglected by authors is the
      subheading Statistical analysis, within Materials and methods, where authors must
      explain which statistical tests were used in their data analysis and the
      rationale for using those tests. They also need to make sure that all tests used
      are listed under Statistical analysis section, as well as that all tests listed
      are indeed used in the study. When writing Results section there are several key
      points to keep in mind, such as: are results presented with adequate precision
      and accurately; is descriptive analysis appropriate; is the measure of confidence
      provided for all estimates; if necessary and applicable, are correct statistical
      tests used for analysis; is P value provided for all tests, etc. Especially
      important is not to make any conclusions on the causal relationship unless the
      study is an experiment or clinical trial. We believe that the use of the proposed
      checklist might increase the quality of the submitted work and speed up the peer
      review and publication process for published articles.

PMID- 22384517
TI  - Free DNA--new potential analyte in clinical laboratory diagnostics?
AB  - The existence of cell free DNA in the human circulatory system has been known
      since the 1950s, however, intensive research in this area has been conducted for
      the last ten years. This review paper brings a short overview of the existing
      literature concerning the cell free DNA research in various clinical fields and
      pathological states and considers the application possibilities of this new
      analyte in clinical laboratory diagnostics. At the moment, cell free DNA is most
      widely used for the purpose of non-invasive prenatal diagnosis of fetal sex or
      fetal RhD status. The recent discovery of epigenetic changes in placental/fetal
      DNA and the detection of fetal/placental-specific RNAs have made it possible to
      use this technology in all pregnancies irrespective of the gender of the fetus.
      With the application of new techniques such as next generation sequencing,
      digital PCR and mass spectrometry, it is now possible to detect very small
      amounts of specific DNA in the presence of excess of other nonspecific nucleic
      acids. Second most probable application is in oncology, where detection and
      monitoring of tumors is now possible by the detection of tumor-derived nucleic
      acids. Third promising field for near future implementation of this analyte is
      transplantation medicine, where free DNA level could serve as a marker of
      transplant rejection. Before any further utilization of this new biomarker, pre
      analytical and analytical aspects of free DNA analysis remain to be standardized.
      In the field of noninvasive prenatal diagnosis, important ethical, legal and
      social questions remain to be discussed.

PMID- 22384518
TI  - The role of CRP and inflammation in the pathogenesis of age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is a complex, degenerative and progressive
      disease involving the multiple genetic and environmental factors that can result
      in severe visual loss. The etiology of AMD is not well understood. Many theories
      exist and feature mechanisms of oxidative stress, atherosclerotic-like changes,
      genetic predisposition and inflammation. The most recent clinical studies
      appointed to a great role of inflammation and C-reactive protein (CRP) in the
      pathogenesis of AMD. There is a large body of evidence indicating the association
      of CRP with endothelial dysfunction, oxidative stress and production of reactive
      oxygen species (ROS), as well as with lipid status disorder in AMD patients.
      According to recent studies, CRP is definitely not only the inflammatory marker
      but also a mediator of development of the vascular disorders in the retinal
      circulation. The results obtained from the present studies may help our
      understanding the pathogenesis of the retinal vascular disease associated with
      high levels of CRP.

PMID- 22384519
TI  - Inflammation and haemostasis.
AB  - Inflammation and haemostasis are interrelated pathophysiologic processes that
      considerably affect each other. In this bidirectional relationship, inflammation
      leads to activation of the haemostatic system that in turn also considerably
      influences inflammatory activity. Such, the haemostatic system acts in concert
      with the inflammatory cascade creating an inflammation-haemostasis cycle in which
      each activated process promotes the other and the two systems function in a
      positive feedback loop. The extensive crosstalk between immune and haemostatic
      systems occurs at level of all components of the haemostatic system including
      vascular endothelial cells, platelets, plasma coagulation cascade, physiologic
      anticoagulants and fibrinolytic activity. During inflammatory response,
      inflammatory mediators, in particular proinflammatory cytokines, play a central
      role in the effects on haemostatic system by triggering its disturbance in a
      number of mechanisms including endothelial cell dysfunction, increased platelet
      reactivity, activation of the plasma coagulation cascade, impaired function of
      physiologic anticoagulants and suppressed fibrinolytic activity. The two examples
      of pathophysiologic processes in which the tight interdependent relationship
      between inflammation and haemostasis considerably contribute to the pathogenesis
      and/or progression of disease are systemic inflammatory response to infection or
      sepsis and acute arterial thrombosis as a consequence of ruptured atherosclerotic
      plaque. Close links between inflammation and haemostasis help explain the
      prothrombotic tendency in these two clinical conditions in which inflammation
      shifts the haemostatic activity towards procoagulant state by the ability of
      proinflammatory mediators to activate coagulation system and to inhibit
      anticoagulant and fibrinolytic activities. This review summarizes the current
      knowledge of the complex interactions in the bidirectional relationship between
      inflammation and haemostasis.

PMID- 22384520
TI  - Uric acid as one of the important factors in multifactorial disorders--facts and
      controversies.
AB  - With considering serum concentration of the uric acid in humans we are observing
      hyperuricemia and possible gout development. Many epidemiological studies have
      shown the relationship between the uric acid and different disorders such are
      obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians
      and investigators recognized serum uric acid concentration as very important
      diagnostic and prognostic factor of many multifactorial disorders. This review
      presented few clinical conditions which are not directly related to uric acid,
      but the concentrations of uric acid might have a great impact in observing,
      monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a
      marker of oxidative stress. Production of the uric acid includes enzyme xanthine
      oxidase which is involved in producing of radical-oxigen species (ROS). As by
      products ROS have a significant role in the increased vascular oxidative stress
      and might be involved in atherogenesis. Uric acid may inhibit endothelial
      function by inhibition of nitric oxide-function under conditions of oxidative
      stress. Down regulation of nitric oxide and induction of endothelial dysfunction
      might also be involved in pathogenesis of hypertension. The most important and
      well evidenced is possible predictive role of uric acid in predicting short-term
      outcome (mortality) in acute myocardial infarction (AMI) patients and stroke.
      Nephrolithiasis of uric acid origin is significantly more common among patients
      with the metabolic syndrome and obesity. On contrary to this, uric acid also acts
      is an "antioxidant", a free radical scavenger and a chelator of transitional
      metal ions which are converted to poorly reactive forms.

PMID- 22384521
TI  - Association between 11beta-hydroxysteroid dehydrogenase type 1 gene polymorphisms
      and metabolic syndrome in Bosnian population.
AB  - INTRODUCTION: The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      catalyzes the conversion of the hormonally inactive cortisone to active cortisol,
      thus facilitating glucocorticoid receptor activation in target tissues. Increased
      expression of 11beta-HSD1 in adipose tissue has been associated with obesity and
      insulin resistance. In this study, we investigated the association of two 11beta
      HSD1 gene (HSD11B1) polymorphisms with the metabolic syndrome (MetS) and its
      characteristics in the Bosnian population. MATERIALS AND METHODS: The study
      included 86 participants: 43 patients diagnosed with MetS and 43 healthy
      controls. Subjects were genotyped for two HSD11B1 gene polymorphisms: rs846910: G
      > A and rs45487298: insA, by the high resolution melting curve analysis. Genotype
      distribution and an influence of genotypes on clinical and biochemical parameters
      were assessed. RESULTS: There was no significant difference in the mutated allele
      frequencies for the two HSD11B1 gene polymorphisms between MetS patients and
      controls. In MetS patients, no significant associations between disease
      associated traits and rs45487298: insA were found. Regarding rs846910: G >
      Avariant, heterozygous patients (G/A) had significantly lower systolic (P =
      0.017) and diastolic blood pressure (P = 0.015), lower HOMA-IR index (P = 0.011)
      and higher LDL-cholesterol levels (P = 0.049), compared to the wild-type
      homozygotes. In the control group, rs45487298: insA polymorphism was associated
      with lower fasting plasma insulin levels (P = 0.041), lower homeostasis model
      assessment insulin resistance (HOMA-IR) index (P = 0.041) and lower diastolic
      blood pressure (P = 0.048). Significant differences between rs846910: G > A
      genotypes in controls were not detected. Haplotype analysis confirmed the
      association of rs45487298: insA with markers of insulin resistance in the control
      subjects. CONCLUSIONS: Our results indicate that a common rs45487298: insA
      polymorphism in HSD1181 gene may have a protective effect against insulin
      resistance.

PMID- 22384522
TI  - Validation of a laboratory and hospital information system in a medical
      laboratory accredited according to ISO 15189.
AB  - INTRODUCTION: The aim of the study was to present a protocol for laboratory
      information system (LIS) and hospital information system (HIS) validation at the
      Institute of Clinical Chemistry and Laboratory Medicine of the Merkur University
      Hospital, Zagreb, Croatia. MATERIALS AND METHODS: Validity of data traceability
      was checked by entering all test requests for virtual patient into HIS/LIS and
      printing corresponding barcoded labels that provided laboratory analyzers with
      the information on requested tests. The original printouts of the test results
      from laboratory analyzer(s) were compared with the data obtained from LIS and
      entered into the provided template. Transfer of data from LIS to HIS was examined
      by requesting all tests in HIS and creating real data in a finding generated in
      LIS. Data obtained from LIS and HIS were entered into a corresponding template.
      The main outcome measure was the accuracy of transfer obtained from laboratory
      analyzers and results transferred from LIS and HIS expressed as percentage (%).
      RESULTS: The accuracy of data transfer from laboratory analyzers to LIS was 99.5%
      and of that from LIS to HIS 100%. CONCLUSION: We presented our established
      validation protocol for laboratory information system and demonstrated that a
      system meets its intended purpose.

PMID- 22384523
TI  - Nonalcoholic fatty liver disease associated with impairment of kidney function in
      nondiabetes population.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with the
      increased burden of kidney. However, there is still no large population study to
      explore the potential relationship between NAFLD and mild kidney function damage
      (MKFD) after adjusted for confounding factors. This study is to test the
      hypothesis that NAFLD is associated with MKFD under controlling the effects of
      confounding factors. MATERIALS AND METHODS: Levels of serum fasting glucose,
      creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate
      aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and
      physical examination were performed to explore the potential association of NAFLD
      with kidney function. RESULTS: NAFLD was associated with impairment of kidney
      function. Multivariate-adjusted odds ratio illustrated that, compared to subjects
      with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or
      without adjusted for blood glucose and other covariates (P = 0.041). Further
      results from multi-interaction analysis demonstrated that the underlying
      mechanisms linked NAFLD with impaired kidney function may be that they share
      common risk factors and similar pathological processes. CONCLUSIONS: The most
      striking finding of this study is that NAFLD is negatively associated with kidney
      function, in nondiabetic population. NAFLD and MKFD may share similar risk
      factors and/or pathological processes.

PMID- 22384524
TI  - Reproducibility, accuracy and concordance of Accutrend Plus for measuring
      circulating lipid concentration in adults.
AB  - INTRODUCTION: The determination of lipid biomarkers by capillary sampling may be
      useful in the screening, diagnosis and/or personal management of hyperlipidemia
      and cardiovascular risk. It remains unclear whether the use of the Accutrend Plus
      system is appropriate. This study aimed to assess its reproducibility, accuracy
      and concordance for blood lipid profiling in adults. MATERIALS AND METHODS:
      Fasting capillary total cholesterol (TC) and triglyceride (TG) concentration on
      Accutrend Plus were compared with their venous analogues obtained by a laboratory
      reference method in sixty-one adults (27 men and 34 women, aged 33.0 years).
      Supplementary capillary sampling was performed at two consecutive days taking
      into account macro-nutrient intake. RESULTS: The day-to-day reproducibility of
      the Accutrend Plus system proved to be high for TC (ICC = 0.85, P < 0.001), but
      moderate for TG (ICC = 0.68, P < 0.001). Strong correlations (r > or = 0.80, P <
      0.001) with the reference method were found for TC and TG. Mean difference
      (limits of agreement) were: 0.26 mmol/L (-0.95, 1.47) for TC, and -0.16 mmol/L (
      1.29, 0.98) for TG. The concordance for subject classification according to the
      National Cholesterol Education Program (NCEP) guidelines was significant (P <
      0.001), with substantial agreement for TC (K(w) = 0.67), and moderate agreement
      for TG (K(w) = 0.50). CONCLUSIONS: Day-to-day reproducibility of the Accutrend
      Plus device for TC and TG is not optimal and lacks accuracy when compared to the
      reference laboratory method. The concordance between both methods for classifying
      subjects according to the NCEP is inadequate. Accutrend Plus device should not be
      interchangeably used as a substitution for the standard laboratory methods in the
      diagnosis of hyperlipidemia.

PMID- 22384525
TI  - Relationship between serum interleukin-1beta levels and acute phase response
      proteins in patients with familial Mediterranean fever.
AB  - INTRODUCTION: The aim of this study was to investigate whether serum levels of
      interleukin-1beta (IL-1beta) has any possible correlation on inflammatory
      parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)
      and fibrinogen concentration in patients with familial Mediterranean fever (FMF)
      patients during attack-free period. MATERIALS AND METHODS: The serum levels of IL
      1beta, as an indicator of cytokines status, and the acute phase response
      proteins, CRP, ESR and fibrinogen levels were evaluated in 35 attack-free
      patients with FMF and 25 healthy volunteers. RESULTS: Serum IL-1beta levels were
      significantly higher in patients with FMF than control subjects (P = 0.018).
      There was no statistically significant difference in the serum levels of ESR, CRP
      and fibrinogen between two groups (P = 0.181, P = 0.816, P = 0.686,
      respectively). There was a significant correlation between IL-1beta and CRP (r =
      0.513, P = 0.002) values of FMF group. CONCLUSIONS: In conclusion, our results
      confirm the presence of increased IL-1beta levels in FMF patients during attack
      free period. Serum IL-1beta values seems to correlate with CRP levels. The
      elevation of IL-1beta levels may be important in monitoring subclinical
      inflammation of attack free period in FMF patients.

PMID- 22384526
TI  - Investigation of ABCA1 C69T polymorphism in patients with type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Non insulin dependent diabetes mellitus is the most common type of
      diabetes. Genetic factors, lipid profiles, hypertension are potential risk
      factors for diabetes mellitus. Adenosine binding cassette transporter proteins 1
      (ABCA1) plays a role in cholesterol metabolism, especially high density
      lipoprotein (HDL-cholesterol). There are multiple mechanisms by which HDL
      cholesterol can be atheroprotective, it is clear that the relative activity of
      ABCA1 plays a major role. We aimed to investigate association of ABCA1 C69T gene
      polymorphism with lipid levels in Turkish type 2 diabetic patients. MATERIALS AND
      METHODS: After isolation of DNA by ethanol precipitation we determined ABCA1 gene
      polymorphism by using polimerase chain reaction--restriction fragment lenght
      polymorphism (PCR-RFLP) method in 107 type 2 diabetic patients and 50 healthy
      controls. RESULTS: We have observed that the frequency of TT genotype is
      significantly higher in healthy controls compared to patients (14% vs. 3%; P =
      0.008). Also frequency of T allele was higher in controls than in patients (34%
      vs. 21%; P = 0.020; OR (95% CI) = 0.52 (0.30-0.88)). There was no association of
      lipid levels and ABCA1 C69T polymorphism subgroups. CONCLUSION: We have found
      significantly higher frequency of both T allele and genotype in control group
      when compared to patients that made us think that T allele may be a protective
      factor against diabetes mellitus. But, we could not find a relationship between
      genotypes and lipid concentrations in our two groups. Larger studies will help us
      to understand the relationship between ABCA1 C69T genotype and lipid parameters
      in diabetes mellitus.

PMID- 22384527
TI  - Evaluation of the Steelex M600H coagulometer prothrombin time-international
      normalized ratio assay with Steelex test reagents.
AB  - INTRODUCTION: The aim of the present study was to validate prothrombin time (PT)
      international normalized ratio (INR) results obtained using Steelex test reagents
      and a Steelex coagulometer (Steelex Scientific Instrument Company, Beijing,
      China), in comparison with use of a well-established standard test employing
      Pacific Hemostasis reagents (Fisher Diagnostics, Middletown, VA, USA) and Teco
      Coatron A4 coagulometer (Teco Medical Instruments GmbH, Neufahrn, Germany).
      MATERIALS AND METHODS: Between- and within-day coefficients of variation (CVs) of
      both assays were calculated using control samples provided by the test
      manufacturers. Samples from 90 subjects were collected and INR values were
      determined in a double-blind parallel manner employing both systems. RESULTS: The
      within-day coefficients of variation (CVs) in INR estimates ranged from 2.6% (INR
      = 1.12) to 3.1% (INR = 2.51) for the Steelex system and from 2.1% (INR = 1.09) to
      1.8% (INR = 2.8) for the Pacific test; the between-day values ran from 3.4% (INR
      = 1.16) to 7.9% (INR = 2.64) and from 3.3% (INR = 1.1) to 2.3% (INR = 2.7),
      respectively. Passing-Bablok fit of the of the Steelex and Pacific methods
      yielded the equation: Steelex INR = 0.85 (0.79-0.91) x Pacific INR + 0.12 (-0.02
      0.21), whereas the CUSUM linearity P value was < 0.01. The mean bias as
      determined by the Bland-Altman test was -0.156 (-0.912-0.600). CONCLUSION: The
      results obtained using Steelex reagents and the M600H coagulometer are not
      equivalent to those obtained using Pacific Hemostasis reagents and a Teco Coatron
      A4 coagulometer, at least in the therapeutic range.

PMID- 22384528
TI  - Non-commutability of results of highly sensitive troponin I and T immunoassays.
AB  - INTRODUCTION: The measurement of cardiospecific troponins is pivotal in the
      diagnostic and prognostic approach of patients with suspected acute myocardial
      infarction (AMI). However, no information is available on the commutability of
      results between the novel highly-sensitive (HS) troponin T (TnT) and I (TnI)
      immunoassays. MATERIALS AND METHODS: The study population consisted in 47
      consecutive patients presenting at the emergency department (ED) of the Academic
      Hospital of Parma with suspected AMI. TnI was measured with the novel prototype
      Beckman Coulter HS-AccuTnI immunoassay on Access 2, whereas TnT was measured with
      the Roche HS-TnT immunoassay on Cobas. RESULTS: Eight out of the 47 patients
      (17%) were finally diagnosed as having an AMI. The overall correlation between
      TnT and TnI for total patient group was acceptable (r = 0.944; P < 0.01).
      Nevertheless, when the analysis of data was carried out in separate groups
      according to the final diagnosis of AMI, two different equation results were
      obtained, i.e., HS-TnT = HS-AccuTnI x 0.349 + 20 (r = 0.823; P < 0.01) in non-AMI
      patients, and HS-TnT = HS-AccuTnI x 0.134 + 67 (r = 0.972; P < 0.01) in those
      with AMI. CONCLUSIONS: This study suggests the existence of two biological
      relationships between Tnl and TnT in plasma, depending on the source of release
      from the myocardium. Moreover, the non-commutability of data between HS-TnT and
      HS-AccuTnI jeopardizes the clinical decision making, makes it impossible to
      calculate the delta or reference change value using the two biomarkers and to
      finally establish a reliable kinetics of troponin release from the injured
      myocardium.

PMID- 22384529
TI  - Platelet satellitism in a trauma patient.
AB  - Platelet satellitism (PS) is a rare phenomenon observed in blood smears obtained
      from blood anticoagulated with EDTA. It is characterised by platelet rosetting
      around polymorphonuclear neutrophils and in rare cases around other blood cells.
      PS is a rare cause of pseudothrombocytopenia. References about the phenomenon of
      PS in medical literature are few. In this report we describe a case of PS
      fortunately noticed in one trauma patient. Furthermore, we discuss the possible
      pathophysiological mechanisms of PS proposed in the literature. To our knowledge
      this is the first case of PS reported in Croatia.

PMID- 22384530
TI  - [Glucose, body mass index and pre-neoplastic lesions in the cervix].
AB  - BACKGROUND: The obesity and abnormal blood glucose level has been associated with
      cervical cancer development; however, few studies have been performed about this
      relation. OBJECTIVE: Evaluate the blood glucose levels and body mass index (BMI)
      in women with human papilloma virus infection (HPV-I) and cervical
      intraepithelial neoplasia (CIN-I). PATIENTS AND METHOD: Transversal study of 44
      women diagnosed with HPV-I and CIN-I from September to December 2010 in Dysplasia
      Clinic of Regional Hospital of Guzman City, Federal entity of Jalisco, Mexico.
      The diagnoses were carried by biopsy of cervix, glucose test results were
      evaluated by spectrophotometry and determinate the BMI. RESULTS: The 18% (n=8) of
      women were without injury, 41% (n=18), with HPV-I and 41% (n=18) CIN-I. High
      blood glucose was observed in GIN-I versus without injury in the cervix (p =
      0.05), the correlation was OR = 2.6 (95% CI: 1.090-6.52). The young women (19-35
      years) were 17% high glucose, 28% normal glucose and 55% low glucose. In group of
      the medium age (35-65 years) 23% showed high glucose, 50% normal and 27% low. The
      BMI was not relation with diagnosis, although in the age (young versus age median
      p=0.001). CONCLUSION: These results support the proposal about the high levels of
      glucose in plasma and obesity could be risk cofactors in the development of
      preneoplasic lesion of cervix.

PMID- 22384531
TI  - [Cytogenetic diagnosis of first trimester spontaneous abortion].
AB  - BACKGROUND: About 15% of all pregnancies end in abortion. In approximately 60% of
      all losses are chromosomal abnormalities as a cause of pregnancy loss. OBJECTIVE:
      To determine the importance of cytogenetic study in patients with spontaneous
      abortion. MATERIALS AND METHODS: A series of cases of women diagnosed with
      spontaneous abortion less than 12 weeks and cytogenetic studies. Two groups, one
      group of women with normal cytogenetics and group 2 patients with abnormal
      cytogenetic result. 44 patients were excluded by cytogenetic study failed.
      RESULTS: We included 164 women, 55 and 65 for groups 1 and 2, respectively. In 44
      cases the material was not suitable for performing karyotype. Of the 120 cases
      included, had abnormal karyotypes in 65 cases (54%), of which 34 cases (52.3%)
      were trisomy, 16 cases (24.6%) to polyploidy and 9 cases (13.8%) a monosomy. In
      addition, we found six cases (8.7%) with recurrent pregnancy loss. The maternal
      age limit increased incidence of chromosomal abnormalities occurred in the group
      of 31 and 35 years with 20 cases (30%). Of trisomies, the 16 were the
      mostfrequent with 11 cases (32.3%). CONCLUSIONS: The finding of 54% of
      chromosomal abnormalities in spontaneous abortion products demonstrates the
      importance of cytogenetic study, regardless of patient age and number of previous
      pregnancy losses.

PMID- 22384532
TI  - [Consensus for the prevention of cervical cancer in Mexico].
AB  - Cervical cancer remains a serious public health problem in the world; that is why
      the Mexican Federation of Schools of Obstetrics and Gynecology convened the
      elaboration of a consensus that is devoted this number of Ginecologia y
      Obstetricia de Mexico. In recent years has strengthened perceptions (public and
      private) in the need for preventive strategies in the medium and long terms. The
      development of effective vaccines against the human papilloma virus and the
      application of new methods of detection from viral DNA (completely automated for
      personal application) allow some degree of optimism. It is proposed a consensus
      with general recommendations in two consecutive stages: (a) primary prevention
      consisting of education for the prevention of cervical cancer and universal
      immunization and (b) secondary prevention by early detection of infections or
      injuries that could favor carcinogenesis. The consensus reviewed characteristics
      of available vaccines in detail and proposes strategies for implementation in
      Mexican population. Also, check out main methods of early detection of infection
      (or predisposing lesions) and suggests public and private strategies for
      implementation. Consensus places particular emphasis on early immunization for
      female population and correct use of methods for detection of infections or
      injuries that might cause cervical cancer.

PMID- 22384533
TI  - [Consensus for the prevention of cervical cancer in Mexico. The burden of
      cervical cancer and infection by human papilloma virus in Mexico and
      internationally].

PMID- 22384534
TI  - [Primary prevention of cervical cancer].

PMID- 22384535
TI  - [Benefits and risks of vaccination against human papilloma virus].

PMID- 22384536
TI  - [Secondary prevention (screening) of cervical cancer].

PMID- 22384537
TI  - [Conclusions of the consensus for the prevention of cervical cancer in Mexico].

PMID- 22384538
TI  - Implementing ORNAC's strategic plan will require the involvement of all of
      Canada's perioperative registered nurses.

PMID- 22384539
TI  - A descriptive study exploring the principles of asepsis techniques among
      perioperative personnel during surgery.
AB  - BACKGROUND: Perioperative nurses are expected to demonstrate strict adherence
      with asepsis principles to prevent surgical site infections (SSIs) as breaching
      of these principles poses a serious risk of infection to surgical patients.
      METHODS: A descriptive survey was conducted with a convenience sample of 87
      perioperative personnel to describe self-reported compliance with the principles
      of asepsis during surgery. PURPOSE: The purpose of this study was to examine the
      practices of perioperative scrub personnel with surgical asepsis. RESULTS: A
      sizable percentage of participants indicated that they never or rarely observe
      breaches in the sterile field during surgery with regards to open suction drain
      systems (46.6%; n = 41), closed suction drain systems (46.6%; n = 41), suture
      material (39.7%; n = 35), use of surgical instruments (37.5%; n = 33), and
      prosthetic implants (56.8%; n = 50). Perioperative scrub RNs were less likely to
      wear shoe covers during surgical procedures than ORTs (M = 3.42 and 4.17; mdn =
      3.00 and 5.00 respectively; p = .026). CONCLUSIONS: The findings showed areas of
      compliance and noncompliance with the principles of asepsis. Given that the role
      of the perioperative nurse is paramount in maintaining surgical integrity, and
      enhancing positive patient outcomes, strict adherence to surgical asepsis is
      vital to prevent SSIs and other complications.

PMID- 22384540
TI  - [Progress and debates of polycystic ovary syndrome treated by integrative
      medicine].

PMID- 22384541
TI  - [Regulation and control of wenshen yangxue granule combined with clomifene
      citrate on INH-ACT-FS system in patients with follicular maldevelopment
      infertility].
AB  - OBJECTIVE: To observe the clinical curative effect of Wenshen Yangxue Granule
      (WSYXG) combined with clomifene citrate (CC) in treating follicular
      maldevelopment (FM) infertility, and to explore its possible action channels.
      METHODS: Ninety patients with FM of Shen-deficiency blood stasis syndrome were
      randomly assigned to 3 groups, i.e., the Chinese medicine group (CMG, treated
      with WXYXG), the Western medicine group (WMG, treated with CC), and the
      combination group of Chinese medicine and Western medicine (CG, treated with both
      WSYXG and CC), 30 cases in each group. Three menstrual cycles were totally
      observed. Serum levels of luteinizing hormone (LH), follicle stimulating hormone
      (FSH), estradiol (E2 ), inhibin B (INHB), activin A (ACTA), and follistatin (FS)
      were tested before and after treatment, and the ovulation was monitored and their
      basic body temperature measured. RESULTS: There was no statistical difference in
      clinical efficacy among the three groups (P> 0.05). Better effects on the Chinese
      medicine syndrome efficacy, the ovulation rate, and the endometrium thickness on
      the ovulation day were shown in CMG and CG than in WMG, showing statistical
      difference (P < 0.05). The E2 level increased on the third day of the first
      menstrual cycle in CG when compared with before treatment. On the 10th day of the
      1st menstrual cycle, the INHB and FS increased and the ACTA decreased, showing
      statistical difference (P < 0.05). On the 10th day of the 3rd menstrual cycle the
      serum LH level decreased more obviously in CG than in WMG, showing statistical
      difference (P < 0.05). On the 3rd day of the 3rd menstrual cycle in CG, the INHB
      was negatively correlated with FSH (r = -0.492,P < 0.01), and INHB on the 10th
      day was positively correlated with E2 and FS (r = 0.682, 0.772, P < 0.01), and
      negatively correlated with ACTA on the 10th day (r = -0.635, P < 0.01).
      CONCLUSION: WSYXG combined with CC could improve Chinese medicine syndrome,
      regulate the expressions of FM patients' ovary local factors INHB, ACTA and FS,
      improve the condition of ovary functions, and control the follicle development.

PMID- 22384542
TI  - [Clinical observation of erhuang powder's promoting the wound healing of cervical
      columnar epithelium ectopy after physiotherapy].
AB  - OBJECTIVE: To observe the clinical effects of Erhuang Powder (EHP) in promoting
      the wound healing of cervical columnar epithelium ectopy after physiotherapy.
      METHODS: Sixty-four patients with moderate and severe cervical columnar
      epithelium ectopy accompanied with contact bleeding were assigned to the
      treatment group (34 cases) and the control group (30 cases) according to table of
      random digit. Physiotherapy of the cervix was given to all patients. EHP was
      externally applied to the affected site of patients in the treatment group once
      every 3 days. Five times consisted as one therapeutic course, totally for 2
      courses. The therapeutic effects, the wound healing time, the vaginal fluid
      quantity, the vaginal fluid discharge time, the wound infection, and adverse
      reaction were observed in the two groups. RESULTS: The healing rate of the
      treatment group was 85.29% (29/34), higher than that of the control group (50%,
      15/30) after 8 weeks of treatment, showing statistical difference (P < 0.1). The
      average wound healing time of the treatment group (3.2 - 0.8 weeks) was shorter
      than that of the control group (5.3 +/- 0.9 weeks), showing statistical
      difference (P < 0.5). The vaginal fluid quantity and the vaginal fluid discharge
      time in the treatment group were superior to those in the control group, showing
      statistical difference (P < 0.5, P < 0.1). Increased vaginal secretion
      accompanied with foreign odor or infection occurred in 2 patients of the control
      group. No adverse reaction or infection occurred in the treatment group.
      CONCLUSIONS: Local application of EHP could promote the wound healing of cervical
      columnar epithelium ectopy after physiotherapy. It could improve its healing
      rate. Therefore, it was one ideal and reliable method, and worthy of clinical
      spreading.

PMID- 22384543
TI  - [Clinical effects of shen-nourishing and menstruation-regulating method combined
      with triptorelin acetate injection on patient with luteinized unruptured follicle
      syndrome].
AB  - OBJECTIVE: To study the clinical effects of Shen-nourishing and menstruation
      regulating method (SNMRM) combined with Triptorelin Acetate Injection (TAI) on
      patients with luteinized unruptured follicle syndrome (LUFS). METHODS: Sixty-two
      LUFS patients were randomly assigned to the treatment group and the control
      group. TAI was given to patients in the control group while SNMRM + TAI was given
      to those in the treatment group. The ovulation rate and the pregnancy rate were
      observed in the two groups. RESULTS: The ovulation rate in the treatment group
      was higher than that in the control group, but without significant difference
      (85.53% versus 79.07%, P > 0.05). The pregnancy rate was significantly higher in
      the treatment group than in the control group (56.25% vs 30.00%, P < 0.05).
      CONCLUSION: Treatment of LUFS by SNMRM + TAI could improve the ovulation rate and
      the pregnancy rate, indicating that LUFS patients' ovary functions could be
      improved by using different menstruation regulating methods during different
      follicular development phases.

PMID- 22384544
TI  - [Effects of xuezhikang at different doses on patients suffering from acute
      coronary syndrome after percutaneous coronary intervention].
AB  - OBJECTIVE: To study the effects Xuezhikang (XZK) at different doses on
      inflammatory factors and blood lipids of patients suffering from acute coronary
      syndrome (ACS) after percutaneous coronary intervention (PCI) and to discuss
      their safety. METHODS: Eighty ACS in patients receiving selective PCI treatment
      were randomly assigned to two groups, 40 cases in the normal dose group and 40
      cases in the large dose XZK group. Besides routine therapy, all patients took XZK
      at the daily dose of 1.2 and 0. 6 g, twice daily. They started XZK from the very
      day of PCI operation. The therapeutic course for all was more than 8 weeks. The
      levels of high sensitivity C reactive protein (hs-CRP) and matrix
      metalloproteinase-9 (MMP-9) were detected in the two groups 1 week, 4 and 8 weeks
      after operation. The levels of TC, TG, HDL-C, LDL-C, changes of liver and renal
      functions were observed. The correlation between blood lipids and inflammatory
      factors were analyzed. The adverse reaction was recorded. RESULTS: Compared with
      before medication, the serum levels of hs-CRP and MMP-9 decreased in the two
      groups 1 week, 4 and 8 weeks after operation, with statistical difference shown
      in the levels at the 8th week (P < 0.05). The decrease was more obvious in the
      large dose XZK group (P < 0.05). The LDL-C level obviously decreased in the two
      groups 4 and 8 weeks after operation (P < 0.05). The decrease was more obvious in
      the large dose XZK group at the 8th week (P < 0.05). The levels of hs-CRP and MMP
      9 were positively correlated with the decrease degree of LDL-C in the large dose
      XZK group at the 8th week (r = 0.828, 0.922, P < 0.05). There was no significant
      difference in the occurrence of adverse reaction, hepatic or renal functions
      between the two groups. CONCLUSIONS: XZK could lower the serum levels of hs-CRP,
      MMP-9, and LDL-C. More obvious effects were obtained in the large dose XZK group.
      The decrease degree of inflammatory factors was correlated with the decrease
      extent of blood lipids.

PMID- 22384545
TI  - [The prevention of denhong injection on contrast-induced renal impairment after
      percutaneous coronary intervention].
AB  - OBJECTIVE: To investigate the prevention of Danhong Injection (DHI) on contrast
      induced renal impairment after percutaneous coronary intervention (PCI). METHODS:
      Eighty patients receiving PCI were randomly assigned to the control group and the
      treatment group, 40 in each. All patients used loperamide injection as the
      contrast media, and received routine medicines such as enteric coated aspirin and
      Betaloc, as well as routine rehydration therapy. As for patients in the treatment
      group, 20 mL DHI was intravenously dripped by adding in 250 mL 0.9% sodium
      chloride injection from 2 -3 days before PCI to 3 days after PCI, once daily. The
      levels of serum creatinine (SCr), cystatin C (CysC), urine micro-albumin (mAlb),
      and beta2-microglobulin (beta2-MG) were measured before PCI, and 24, 48, 72 h
      after PCI. The occurrence of radio contrast-induced nephropathy (RCIN) of the two
      groups was observed. RESULTS: The serum SCr and CysC levels of the two groups
      reached the peak 24 h after PCI (P < 0.05, P < 0.01). But they respectively
      restored to the pre-PCI levels at 48 and 72 h after PCI in the treatment group.
      In the control group the serum SCr level basically restored to the pre-PCI level
      at 72 h after PCI. The urinary mAlb and beta2-MG levels of the two groups reached
      the peak at 24 and 48 h after PCI (P < 0.05, P < 0.01), and basically restored to
      the pre-PCI level at 72 h after PCI. But they did not restore in the control
      group (P < 0.05). Seven patients suffered from RCIN in the two groups, of them 5
      (12.5%) in the control group and 2 (5.0%) in the treatment group, with no
      statistical difference (P > 0.05). CONCLUSIONS: DHI could effectively prevent
      contrast-induced renal impairment and shorten the recovery time of renal
      impairment. It was worth further studies.

PMID- 22384546
TI  - [Effect of naoxintong capsule on the vascular endothelial function and the
      infarct size of patients with acute myocardial infarction].
AB  - OBJECTIVE: To observe the effect of Naoxintong Capsule (NC) on the vascular
      endothelial function and the infarct size of patients with acute myocardial
      infarction (AMI). METHODS: One hundred and four patients with AMI were randomly
      assigned to the NC group (Group A, 36 cases), the Tongguan Capsule group (Group
      B, 32 cases), and the conventional Western medicine group (Group C, 36 cases).
      The conventional Western medicine was given to the three groups. NC was
      additionally given to Group A, and Tongguan Capsule was additionally given to
      Group B. The therapeutic course for all was 4 weeks. The plasma nitric oxide
      (NO), endothelin (ET), von Willebrand factor (vWF) were detected in the 3 groups
      before and after treatment. The inner diameter of brachial artery was examined by
      ultrasonograph. The flow-mediated dilation (FMD) and the nitroglycerin-mediated
      dilation (NMD) were calculated. The ECG QRS integral and the infarct size were
      assessed. RESULTS: There was no significant difference in the vascular
      endothelial function, ECG QRS integral, or the infarct size among the three
      groups before treatment (P > 0.05). Compared with before treatment, NO and NMD
      obviously increased after treatment in Group A and Group B, while the vWF and the
      infarct size obviously decreased in Group A, all showing statistical difference
      (P < 0.05). Compared with those in Group C, the NO, FMD, NMD significantly
      increased and ET obviously decreased in Group A and B after treatment (P < 0.05).
      The ECG QRS integral and the infarct size also decreased, with statistically
      significant differences in Group A (P < 0.05). Better effects on improving NO,
      NMD, and vWF were obtained in Group A than in Group B (P < 0.05). CONCLUSION: NC
      could reduce the infarct size of AMI patients possibly through improving the
      vascular endothelial function.

PMID- 22384547
TI  - [Plasma metabonomic studies on the stable phase chronic obstructive pulmonary
      disease patients of Fei-qi deficiency syndrome and the Chinese materia medica
      intervention].
AB  - OBJECTIVE: By using the metabonomics method, to study the plasma metabonomics of
      the stable phase chronic obstructive pulmonary disease (COPD) patients of Fei-qi
      deficiency syndrome (FQDS), and of Chinese materia medica (CMM) intervention,
      thus exploring possibly existent biomarkers. METHODS: Forty stable phase COPD
      patients of FQDS were recruited as Group A. Liuwei Buqi Capsule (LWBQC) was given
      to them as intervention. A healthy control group (Group B, 37 cases) was set up.
      The pulmonary function test was performed on patients in Group B and Group A
      before and after intervention. The plasma metabolites were detected using high
      performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Statistical
      data were analyzed using principal component analysis (PCA) and partial least
      squares (PLS). The original spectrum and data of plasma metabonomics were
      compared between the two groups. The whole spectrum amino acid metabonomics tests
      were performed in the two groups. RESULTS: Compared with Group B, the pulmonary
      function significantly decreased before intervention in Group A (P < 0.05). The
      pulmonary function was more mildly improved after 30 days' treatment than before
      treatment, but still lower than it in Group B (P < 0.05). The metabolic spectrum
      before treatment in Group A was significantly different from Group B, but showing
      regressive trend to Group B after treatment. Fifteen possible disease markers
      were found in COPD patients of FQDS. Results of the whole spectrum of amino acid
      metabolomics showed different features. CONCLUSIONS: The changes of metabolic
      spectrum and amino acids could be found in the stable phase COPD patients of FQDS
      using plasma metabonomics, and potential markers could be detected. The
      intervention of the stable phase COPD patients of FQDS by Chinese medicine could
      brought positive changes in the metabolic profiling and amino acid metabolism.

PMID- 22384548
TI  - [Study on the correlation between stroke of qi deficiency syndrome and the
      neurological impairment degree and its long-term prognosis].
AB  - OBJECTIVE: To explore the correlation between stroke of qi deficiency syndrome
      (QDS) and the neurological impairment degree, and to study its correlation
      between QDS and its long-term prognosis. METHODS: Recruited were 706 stroke
      patients with complete clinical information including diagnostic scale scoring of
      elements such as wind, fire, phlegm, blood stasis, qi deficiency, and yin
      deficiency, scoring of The National Institutes of Health Stroke Scale (NIHSS)
      within 72 h from attack, on the 7th, 14th, 28th, and 90th day after attack, and
      Barthel index (BI) scoring on the 90th day. They were assigned to the QDS group
      (330 cases) and the non-QDS group (376 cases). The NIHSS scores at different time
      points were compared between the two groups using analysis of variance of
      repeated measure data. The correlation between each syndrome element and the long
      term prognosis of stroke was studied using Logistic regression analysis. RESULTS:
      Higher NIHSS score was found in patients of QDS than those of non-QDS at each
      time point (P < 0.01). Statistical difference existed in NIHSS score between the
      two groups at each time point (P < 0.01, P < 0.05). Besides, NIHSS score
      decreased gradually as time went by. The occurrence frequencies of blood stasis
      syndrome and phlegm syndrome were higher at each time point. On the 90th day
      after attack, 427 patients with BI > or = 95 (accounting for 60%) had favorable
      prognosis, while 279 with BI < 95 (accounting for 40%) had unfavorable prognosis.
      QDS at each time point was negatively correlated with the 90th-day BI, with the B
      value being -0.496, -0.714, -0.867, -0.567, and -0.764, respectively.
      CONCLUSIONS: Stroke patients of QDS had more severe neurological impairment than
      those of non-QDS. Stroke patients of acute-stage QDS was closely correlated with
      unfavorable prognosis on the 90th day after attack. Early actively invigorating
      healthy qi plays an important role in improving the long-term prognosis of stroke
      patients.

PMID- 22384549
TI  - [Study on the quantization diagnostic method for immunoglobulin A nephropathy of
      qi-yin deficiency syndrome].
AB  - OBJECTIVE: To study the method for establishing a quantization diagnostic
      standard for immunoglobulin A (IgA) nephropathy of qi-yin deficiency syndrome
      (QYDS). METHODS: 1,016 patients with primary IgA nephropathy were recruited in
      this study. They were randomly assigned to the training sample group (344 cases
      of QYDS and 456 cases of non-QYDS) and the testing sample group (77 cases of QYDS
      and 139 cases of non-QYDS) using SPSS software. On the basis of epidemiological
      survey, the typing standards for QYDS and common clinical symptoms were taken as
      candidate correlated factors. The correlated factors were selected using binary
      Logistic stepwise regression. The correlated factors were scored using
      conditional probability conversion method. The threshold value of the
      quantization diagnostics was determined using maximum likelihood method. The
      receiver operating characteristic (ROC) curve was drawn to calculate the area
      under curve (AUC), sensitivity, specificity, and accuracy rating. The
      retrospective and prospective tests were performed on the established
      quantization diagnostic standard for QYDS. RESULTS: The quantization diagnosis
      threshold value of IgA nephropathy of QYDS was 12 points. The sensitivity,
      specificity, and accuracy rating of the quantization diagnostic standard were
      75.3%, 68.0%, and 71.1% in the retrospective test, as well as 60.4%, 84.4%, and
      69.0% in the prospective tests. The AUC was 0.80 and 0.78 respectively.
      CONCLUSIONS: It was a feasible method to set up a quantization diagnostic
      standard for IgA nephropathy of QYDS by taking the occurrence frequency of
      symptoms. But this method failed to cover the strength information of symptoms.

PMID- 22384550
TI  - [Clinical and pathological study of weiyan serial recipes in the treatment of
      gastric precancerous lesions].
AB  - OBJECTIVE: To study the therapeutic effect of Weiyan serial recipes (WYSR) in
      treatment of chronic atrophic gastritis (CAG) accompanied with intestinal
      metaplasia (IM) and/or dysplasia (Dys) and to explore its molecular mechanisms
      for reversing the gastric precancerous lesions. METHODS: One hundred and fifty
      patients with confirmed diagnosis of CAG accompanied with IM and/or mild Dys were
      randomly assigned to the treatment group (120 cases) and the control group (30
      cases). Patients in the treatment group were respectively treated with WYSR I-IV
      according to Chinese medicine syndrome typing as incoordination of Gan and Wei
      syndrome (32 cases), deficiency of Pi and Wei syndrome (35 cases), insufficient
      Wei-yin syndrome (28 cases), and stasis stagnation in Wei-channel syndrome (25
      cases). Patients in the control group orally took Weifuchun Pill. The therapeutic
      course for all was 3 months, and totally 2 courses. The clinical effects, changes
      under the gastroscope, the pathological changes, and expressions of gastric
      mucosal hypoxia-inducible factor-1alpha(HIF-1alpha), vascular endothelial growth
      factor (VEGF) protein were compared between the two groups before and after
      treatment. RESULTS: The total effective rate of the treatment group was 86.7% and
      the total effective rate of the gastroscopic changes was 78.3%, which was higher
      than those of the control group (56.7% and 40.0%), showing significant difference
      (P < 0.01, P < 0.05). The total effective rate of clinical symptoms and that of
      the pathological changes were higher in the treatment group than in the control
      group with statistical significance shown (P < 0.05). There was no statistical
      difference in the expressions of HIF-1alpha and VEGF protein of the control group
      between before and after treatment (P > 0.05). Compared with before treatment,
      the post-treatment expressions of HIF-1alpha and VEGF protein both obviously
      decreased in the treatment group (P < 0.01), and were lower than those in the
      control group (P < 0.05). CONCLUSIONS: WYSR showed better effects on treating
      gastric precancerous lesions. It could significantly improve the atrophy, IM, and
      Dys, and promote the reversal of gastric precancerous lesions. Its mechanisms
      might possibly be correlated with inhibiting the over-expressions of HIF-1alpha
      and VEGF protein.

PMID- 22384551
TI  - [Controlling effect of bushen huatan compound on the insulin signal conducting
      molecule inside ovaries in polycystic ovary syndrome model rats].
AB  - OBJECTIVE: To study the effects of Bushen Huatan Compound (BHC) on the glycolipid
      metabolism and the expressions of the insulin signal conducting molecules inside
      ovaries in polycystic ovary syndrome (PCOS) model rats. METHODS: Female Wistar
      rats were subcutaneously injected with 2.5 mg/kg testosterone propionate (Their
      female offspring were randomly divided into the medication group and the model
      group, 10 in each.) or neutral tea oil of the same dose (Ten female offspring was
      taken as the control group.) on the 16th day of pregnancy, once daily, for 3
      successive days. BHC was given to rats in the medication group by gastrogavage,
      while equal volume of distilled water was given to rats in the model group and
      the control group by gastrogavage, both once daily for 20 successive days. The
      body weight and ovary weight were weighed to calculate the ratio of wet fat
      weight/body weight. The blood glucose levels were detected at 0, 0.5, 1, and 2 h
      using oral glucose tolerance test (OGTT). The serum concentrations of high
      density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting blood glucose
      (FBG), and insulin were detected to calculate homeostasis model assessment of
      insulin resistance (HOMA-IR). The expressions of protein kinase B (AKT2),
      glycogen synthase kinase-3beta (GSK3beta), glucose transporter-4 (GLUT4),
      extracellular signal regulated kinase-1 (ERK1) protein, P-AKT2, P-GSK3beta, and P
      ERK1 in ovaries were detected using Western blot. RESULTS: Compared with the
      control group, the ratio of wet fat weight/ body weight, the blood glucose levels
      at 0.5 and 2 h in OGTT, and HOMA-IR all obviously increased, and the HDL-C level
      obviously decreased in the model group (P < 0.05). Compared with the model group,
      the ratio of wet fat weight/body weight and the blood glucose levels at 2 h in
      OGTT obviously decreased, and the HDL-C level obviously increased in the
      medication group (P < 0.05). The expressions of AKT2, P-AKT2, GSK3beta, P
      GSK3beta, GLUT4, and ERK1 in the ovary tissue were obviously lower in the model
      group than in the control group (P < 0.05). The expressions of GSK3beta, P
      GSK3beta, and GLUT4 were more obviously enhanced in the medication group than in
      the model group (P < 0.05). CONCLUSIONS: Insulin resistance and glucolipid
      metabolism dysfunction existed in female PCOS rats. Besides, abnormal insulin
      signaling pathway existed in the ovary tissue. BHC could remarkably ameliorate
      the IR degree and glucolipid metabolism functions, and might be correlated with
      regulating the protein expressions of insulin signal conducting molecules.

PMID- 22384552
TI  - [Study on estrogen receptors alpha and beta in the hippocampus of premenstrual
      syndrome model rats of gan-qi depression syndrome].
AB  - OBJECTIVE: To study the distribution pattern, the protein expressions, and
      changes of functional activities of estrogen receptor (ER) alpha and beta in the
      hippocampus of premenstrual syndrome (PMS) rats of Gan-qi depression syndrome
      (GDS), and to find out corresponding effect targets of Jingqianshu Granule (JG),
      thus providing clues for exploring the pathogenesis of PMS of GDS and the
      mechanisms of JG. METHODS: SD rats were randomly divided into three groups, i.
      e., the normal group, the model group, and the medication group, 7 in each.
      Resident intruder stress was used to establish the model in the model group and
      the medication group. JG was given to rats in the medication group at the dose of
      10 mL/kg by gastrogavage while modeling. Equal volume of sterilized water was
      given to rats in the model group and the normal group, once daily, for 5
      successive days. Then the location, protein levels, and ligand-binding capacities
      of ERalpha and ERbeta in the hippocampus of rats in three groups were detected
      using immunohistochemical assay, Western blot, and dextran-active carbon binding
      assay. RESULTS: There was no difference in the distribution pattern of ERalpha
      and ERbeta in the hippocampus of the three groups. In aspects of protein levels
      and estrogen-binding capacities of ERalpha and ERbeta in the hippocampus, CA1 and
      CA3 regions, they increased more obviously in the model group than in the normal
      group (P < 0.05), while they decreased more significantly in the medication group
      than in the model group (P < 0.05). CONCLUSION: Higher estrogen levels and
      enhanced expressions and activities of ERalpha and ERbeta in the hippocampus
      might be important mechanisms for PMS of GDS, which might also be the effect
      targets for JG.

PMID- 22384553
TI  - [Proteomic study of total protein of Pinellia pedatisecta Schott effect on human
      ovarian cancer SKOV3 cells].
AB  - OBJECTIVE: To study the proteomics of Pinellia pedatisecta Schott total protein
      on human ovarian cancer SKOV3 cells. METHODS: SKOV3 cells were in vitro cultured.
      The growth inhibition of SKOV3 cells in the logarithmic phase with different
      concentrations of Pinellia pedatisecta Schott (0, 0.05, 0.10, 0.20, 0.30, 0.40,
      and 0.50 mg/mL) at different time points (24, 48, 72, and 96 h) was analyzed by
      CCK-8 colorimetry. The total protein was extracted after adding 0.296 mg/mL
      Pinellia pedatisecta Schott protein for 48 h. The protein with differential
      expressions was screened out using two-dimensional gel electrophoresis (2-DE) and
      matrix-assisted laser desorption ionization time of flight mass spectrometry
      (MALDI-TOF-MS). RESULTS: The protein of Pinellia pedatisecta Schott (at 0.10 -
      0.50 mg/mL) could significantly inhibit the growth of SKOV3 cells in a time- and
      dose-dependent manner (P < 0.05, P < 0.01). After analyzed by 2-DE and MALDI-TOF
      MS, 43 differential protein dots were successfully identified (21 up-regulated
      and 22 down-regulated), including alpha-enolase 1, eukaryotic initiation factor
      3alpha, cyclophilin B, and so on. CONCLUSIONS: Protein of Pinellia pedatisecta
      Schott could significantly inhibit the growth of SKOV3 cells, and lead to the
      proteomics changes of SKOV3 cell strain. They might be correlated with its anti
      tumor mechanisms.

PMID- 22384554
TI  - [Intervention of rukangyin on the lymphangiogenesis in breast cancer metastasis
      nude spontaneous mouse model].
AB  - OBJECTIVE: To observe the effects of rukangyin (RKY) on the lymphangiogenesis and
      lymph node metastasis of breast cancer transplantation tumor mice, thus exploring
      its anti-tumor metastasis mechanisms. METHODS: Human breast cancer cell line MDA
      MB-435S were in situ implanted into the mammary fat pad of 30 female nude mice to
      establish breast cancer transplantation tumor spontaneous metastasis model. They
      were randomly divided into six groups, i.e., the model control group, the 5-FU
      control group, the small, medium, large dose RKY groups, and the medium dose RKY
      +5-FU group, 5 in each. Normal saline was given to mice in the model control
      group at the daily dose of 0.4 mL/kg by gastrogavage. 5-FU was given to mice in
      the 5-FU control group at the daily dose of 30 mg/kg by peritoneal injection. RKY
      was given to mice in the small, medium, large dose RKY groups at the daily dose
      of 18, 45, and 90 g/kg by gastrogavage. 5-FU 30 mg/kg (by peritoneal injection) +
      RKY 45 g/( kg x d) (by gastrogavage) was given to mice in the medium dose RKY +5
      FU group. All medication was carried out once daily for 6 successive weeks. The
      tumor volume, the tumor inhibition ratio, and the inhibition ratio of axillary
      lymph node metastasis were detected after medication. The lymphatic microvessel
      density (LMVD) and expressions of vascular endothelial growth factor-C (VEGF-C)
      and vascular endothelial growth factor receptor-3 (VEGFR-3) of the breast cancer
      tissues were detected using immunohistochemical assay. RESULTS: Compared with the
      model control group, the tumor volume was markedly reduced in the small, medium,
      large dose RKY groups, and the medium dose RKY +5-FU group, the expressions of
      VEGF-C and VEGFR-3 were significantly down-regulated and LMVD were obviously
      lowered, showing statistical difference (P < 0.05, P < 0.01). The inhibition
      rates of tumor and axillary lymph node metastasis were highest and the LMVD was
      the lowest in the medium dose RKY +5-FU group, showing statistical difference
      when compared with other medication groups (P < 0.05, P < 0.01). CONCLUSION: RKY
      might inhibit the lymph node metastasis of breast cancer possibly through
      intervening the expressions of VEGF-C and VEGFR-3, and suppressing
      lymphangiogenesis.

PMID- 22384555
TI  - [Effects of zuogui pill on the gene expressions of Type- II collagen and
      proteoglycan during the differentiation of mesenchymal stem cells towards
      chondrocytes].
AB  - OBJECTIVE: To study the effects of zuogui pill (ZP) contained serum on the gene
      expressions of type-II collagen and proteoglycan during the differentiation of
      mesenchymal stem cells (MSCs) towards chondrocytes. METHODS: MSCs isolated from
      rat bone marrow were in vitro induced differentiation towards chondrocytes and
      stimulated with high- (57 g/kg), middle- (28.5 g/kg), and low-dose (9.5 g/kg) ZP
      contained serums and serum of blank rats. The proliferation of MSCs was analyzed
      by CCK-8 method. The 3rd-passage MSCs were divided into the blank control group
      (by adding serum of the blank group rats), the induction control group (by adding
      the induction fluid and serum of the blank group rats), and the ZP contained
      serum group (by adding the induction fluid and middle-dose ZP contained serum).
      The expressions of type-II collagen and proteoglycan were determined using
      reverse transcriptase PCR, Real-time PCR, and immunohistochemistry. RESULTS:
      Compared with the blank control group, the proliferation of MSCs could be
      promoted by ZP contained serum at different doses (P < 0.05), with the most
      obvious effect shown in the middle-dose ZP contained serum group (P < 0.05). The
      mRNA and protein expressions of type-II collagen could be identified in the
      induction control group and the ZP contained serum group on the 21st day of the
      induction. Of them, the mRNA expression of type-II collagen in ZP contained serum
      groups was obviously higher than that of the induction control group. Results of
      Real-time PCR showed that on the 21st day of the induction, the mRNA expression
      quantitation of proteoglycan in ZP contained serum groups was about 16-fold and 3
      fold of the levels on the 7th day and the 14th day (P < 0.05), obviously higher
      than those of the induction control group (P < 0.05). CONCLUSION: ZP contained
      serum could induce MSCs proliferation, the gene expressions of type- II collagen
      and proteoglycan, which might be one of its molecular bases for protecting the
      cartilage.

PMID- 22384556
TI  - [Effects of licorice on p53 mRNA stability and expression during the
      proliferation of intestinal crypt stem cells].
AB  - OBJECTIVE: To study the effects of licorice on the proliferation of intestinal
      crypt stem cell line IEC-6 and the expression of p53. METHODS: Induced by
      difluoro-methylornithine (DFMO), polyamine-depleted IEC-6 cells under growth
      inhibition were used as the pathological cell model in this study. Cells were
      divided into four groups, i. e., the control group, the DFMO-treated group, the
      high dose licorice group, and the low dose licorice group. The control group
      consisted of IEC-6 cells cultured in normal condition. The other three groups
      were all treated with 5 mmol/L DFMO. The high dose and low dose licorice groups
      were supplemented with 40 and 80 microg/mL licorice granule respectively. All the
      groups were cultured for 6 successive days. The cell number and viability were
      determined using flow cytometry. The level of p53 protein was detected by Western
      blot. The p53 mRNA levels and stability were detected using fluorescent
      quantitative Real-time PCR. RESULTS: Compared with the control group, the cell
      growth of the DFMO group was obviously inhibited on the 4th day (P < 0.05). The
      cell number increased more obviously in the low dose licorice and the high dose
      licorice groups in a dose-dependent way on the 6th day when compared with the
      DFMO group (P < 0.05). When compared with the control group, significantly
      elevated expression levels of p53 protein and mRNA in cells of the DFMO group
      were detected after 6-day treatment (P < 0.05). When compared with the DFMO
      group, the expression levels of p53 protein and mRNA were significantly down
      regulated in the low dose licorice and the high dose licorice groups (P < 0.05).
      The degradation of p53 mRNA was the fastest in the control group, while the
      degradation speed of cells in the DFMO group was the slowest. CONCLUSION: One of
      mechanisms for protective and healing effects of licorice on the intestinal
      mucosa was possibly through down-regulating the stability of p53 mRNA, lowering
      the expression of p53, thus promoting the proliferation of the intestinal crypt
      stem cells.

PMID- 22384557
TI  - [Study of flavanoids extracted from onion on the blood-brain barrier permeation
      and neuroprotective effects].
AB  - OBJECTIVE: To study the flavanoids extracted from onion on the blood-brain
      barrier (BBB) permeation, and their effects on primary cultured neuron cell
      proliferation and apoptosis of SD rats using ethanol reflux method. METHODS: The
      brain microvascular endothelial cells (BMVECs) were first successfully primary
      cultured. Then rats BMVECs and astrocytes (ACs) were co-cultured to establish the
      in vitro BBB model. The flavanoids were extracted from onion using ethanol reflux
      method. The model was verified by transmission electron microscopy (TEM) and
      trans-epithelial electric resistance (TEER). The flavanoids permeability was
      tested using high performance liquid chromatography (HPLC). Meanwhile, rat neuron
      cells were cultured and exposed to H2O2 and flavanoids. Their effects on the cell
      proliferation and apoptosis were observed using MTT assay. The injury of neuron
      DNA was analyzed using single-cell gel electrophoresis (SCGE) and
      immunofluorescent assay. RESULTS: The in vitro BBB model was successfully
      established by TEM and TEER. Results of HPLC proved flavanoids extracts could
      effectively permeate the BBB with the permeability of 60.58%. The extractive at
      10 - 20 microg/mL showed obvious inhibition on the apoptosis of neuron cells
      induced by H2O2, and attenuated the injury of neuron DNA. CONCLUSIONS: The
      flavanoids extracted from onion ethanol reflux method could effectively penetrate
      the BBB. They also showed obvious inhibition on the H2O2 induced neuron cell
      apoptosis and DNA injury.

PMID- 22384558
TI  - [Effects of compound danshen dripping pill on the structure and functions of
      sternohyoid muscle in metabolic syndrome rats].
AB  - OBJECTIVE: To study the effects of Compound Danshen Dripping Pill (CDDP) on the
      structure and functions of sternohyoid muscle in metabolic syndrome (MS) rats,
      and to study whether it has therapeutic effects on obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: Twenty-one healthy male SD rats were randomly
      divided into three groups, i.e., the normal control group (n = 6), the MS group
      (n = 8), and the CDDP group (n = 7). Rats in the normal control group were
      routinely fed. High lipid forage was given to rats in the rest two groups. Nine
      weeks later, CDDP (at the dose of 375 mg/kg) was additionally given to rats in
      the CDDP group by gastrogavage, and then rats in the CDDP group and the MS group
      were fed with the same high lipid forage for 12 successive weeks. The content of
      malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) in the
      sternohyoid muscle were detected in the three groups. The capillary density,
      capillary-to-fiber ratio (C/F), the section area of type I muscle fiber were
      detected using myosin-ATPase histochemical assay. The contractile changes of
      isometric stemohyoid muscles were determined under electric stimulation by
      different frequencies. RESULTS: The contents of MDA were obviously lower in the
      CDDP group than in the MS group, while the activities of SOD, the capillary
      density, C/F, the section area of type I muscle fiber, the tension of stemohyoid
      muscle at 10 -60 Hz, and the 1-5 min tension percentages of the stemohyoid muscle
      were higher in the CDDP group than in the MS group (P < 0.05, P < 0.01).
      CONCLUSION: CDDP could improve oxidative stress induced intramuscularly
      microcirculation disturbance and changes of muscular fiber structures of the
      upper airway muscles, and elevate their contractile functions, thus possibly
      contributing to favorable effects on OSAHS.

PMID- 22384559
TI  - [Langohuangping granule down-regulated monocyte chemoattractant protein-1 via
      suppressing nuclear factor kappa B signaling pathway in BXSB lupus nephritis
      mice].
AB  - OBJECTIVE: To study whether Langchuangping granule (LG) could exert its renal
      protection by down-regulating monocyte chemoattractant protein-1 (MCP-1) via
      suppressing nuclear factor kappa B (NF-kappaB) signaling pathway in BXSB lupus
      nephritis (LN) mice. Methods Eighteen male 11-week-old BXSB LN mice were randomly
      divided into three groups, i.e., the model group, the hormone group, and the
      Chinese medicine group, 6 in each. They were administered by gastrogavage with
      normal saline, methylprednisolone, and LG, respectively. Another six C57BL/6 male
      mice of the same age was taken as the normal control group, which was
      administered with normal saline by gastrogavage. All mice were treated once
      daily, for 4 successive weeks. The 24-h urine protein was determined. The mRNA
      and protein expressions of MCP-1 in the renal tissue were detected using RT-PCR
      and Western blot. The expression of NF-kappaB p65 in the renal tissue was
      detected using immunohistochemical assay. Activity index (AI) of the renal tissue
      was counted using PAS stain. The content of ds-DNA antibody was detected using
      ELISA. The correlations of the aforesaid indices were analyzed. RESULTS: The 24-h
      urine protein level, serum ds-DNA antibody content, protein and mRNA expressions
      of MCP-1, NF-kappaB p65 expression level, and AI count were obviously higher in
      the model group than in the normal control group (P < 0.01). The aforesaid
      indices all obviously decreased after medication in the Chinese medicine group
      and the hormone group (P < 0.05). MCP-1 protein expression level was positively
      correlated with MCP-1 mRNA, NF-kappaB p65, AI, 24-h urine protein, and ds-DNA
      antibody of all LN mice (r= 0.984, 0.936, 0.887, 0.698, 0.679, all P < 0.01).
      CONCLUSIONS: LG possibly played renal protection by down-regulating NF-kappaB
      mediated MCP-1 expression levels. MCP-1 played important roles in the occurrence
      and development of LN, being one of ideal targets for LN treatment.

PMID- 22384560
TI  - [Effect of growth hormone combined with Radix Dipsaci on the body growth and the
      bone metabolism of hypophysectomized rats].
AB  - OBJECTIVE: To study the effect of growth hormone (GH) combined with Radix Dipsaci
      on the body growth and the bone mineral content (BMC) of hypophysectomized rats.
      METHODS: The GH deficiency rats model was established using the hypophysectomized
      operation through the skull and the throat. Qualified rats were divided into the
      sham-operation group (n = 15), the negative control group (n = 13), the GH
      intervention group (n = 13), and the GH combined with Radix Dipsaci group(n =
      12). GH (0.25 mg/kg) was subcutaneously injected from the cervical part in the GH
      intervention group and the GH combined with Radix Dipsaci group at the same time,
      while equal volume of normal saline was injected to the rest groups. 0.7 mL/100
      kg Radix Dipsaci was given by gastrogavage to the GH combined with Radix Dipsaci
      group at the same time, while equal volume of normal saline was given by
      gastrogave to the rest groups. The body weight, the tail length, and the body
      length were measured during the intervention period. Blood was withdrawn after 14
      day intervention. The femoral bone and the tibial bone were taken out. The levels
      of GH, insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), and
      osteocalcin (OC) were measured. The width of the tibial epiphyseal plate was
      measured. The bilateral femur bone mineral density (BMD) and BMC were measured
      using the dual energy X-ray absorptiometry. RESULTS: The body weight, the body
      length, the length of the femoral bone, the length of the tibial bone, the width
      of the epiphyseal plate, the levels of the GH, IGF-1, ALP, and OC increased in
      the GH intervention group and the GH combined with Radix Dipsaci group after 2
      week intervention, showing statistical difference when compared with the model
      group (P < 0.01). But there was no statistical difference in the tail length
      though it also increased (P > 0.05). There was insignificant difference in the
      aforesaid indices between the two groups (P > 0.05). Compared with the model
      group, the BMD of the GH combined with Radix Dipsaci group increased with
      statistical difference (P < 0.01). Compared with the model group, the BMC of the
      GH intervention group and the GH combined with Radix Dipsaci group increased with
      statistical difference (P < 0.01). It was highest in the GH combined with Radix
      Dipsaci group (P < 0.01). CONCLUSIONS: GH combined with Radix Dipsaci showed
      unobvious effect on promoting the growth. But it could elevate BMD and BMC, and
      improve the bone metabolism.

PMID- 22384561
TI  - [The establishment of research inherit mode of famous academic thoughts].
AB  - To study and summarize the academic thoughts of famous Chinese medicine doctors
      is the main pathway of developing Chinese medicine theories. It is of important
      significance in enriching and developing the Chinese medicine theories by
      combining traditional and modern research methods, merging multiple disciples to
      study the research inherit mode of famous academic thoughts. The major study
      links include: (1) To refine scientific hypotheses from huge amount of clinical
      case records; (2) To find the literature sources; (3) To embody the practice
      significance of the innovative theories by clinical studies; (4) To reveal the
      scientific connotation of Chinese medicine theories by experimental studies. We
      hope to reach the goal of innovating and developing Chinese medicine theories on
      the basis of inheritance by integrating clinical case records, tracing the
      literature sources, clinical and experimental studies.

PMID- 22384562
TI  - [Computer-assisted anatomical evaluation of the nasal sinuses in infants].
AB  - OBJECTIVE: To analyze the anatomical and developmental characteristics of nasal
      sinuses in infants; and provide potential evidence for the diagnosis and
      treatment of sinusitis in infants. METHOD: Coronal CT scans for 36 infants (72
      sides) were studied with the imaging station. Reference data were identified on
      these images using imaging station. The gasification conditions of the sinuses
      were identified and measured. RESULT: 100% of the frontal sinuses were absent,
      while 100% of the maxillary sinuses were developed. The mean of the transverse
      and vertical diameters for the left side of the maxillary sinuses was (8.69 +/-
      3.75) mm and (9.37 +/- 2.36) mm, respectively. While those for the right side
      were (8.95 +/- 2.79) mm and (9.06 +/- 2.66) mm, respectively. All of the anterior
      and posterior ethmoid sinuses were developed. The mean transverse and vertical
      diameters for the left side of the anterior ethmoid sinus were (3.63 +/- 1.17) mm
      and (8.21 +/- 2.72) mm, respectively. While those mean for its right side were
      (3.48 +/- 1.32) and (8.28 +/- 2.62) mm, respectively. The mean transverse and
      vertical diameters for the left side of the posterior ethmoid sinus were (4.09 +/
      1.13) mm and (6.61 +/- 1.36) mm, respectively. While those for the right side
      were (4.01 +/- 1.28) mm and (6.63 +/- 1.97) mm, respectively. 30.6% (22 sides) of
      the sphenoid sinuses were developed, while 69.4% (50 sides) were not. CONCLUSION:
      The nasal sinuses in infants have already developed. The development of the
      maxillary and ethmoid sinuses was clear and definite. The pneumatization of the
      sphenoid sinus was defined in some babies, however, the pneumatization of the
      frontal sinus was not defined in all babies.

PMID- 22384563
TI  - [Study for the histopathologic change of ethmoid bone in patients with chronic
      rhinosinusitis and its correlation factors].
AB  - OBJECTIVE: To investigate the histopathologic changes of ethmoid bone and its
      correlation with clinical types of chronic rhinosinusitis (CRS). METHOD: All
      ethmoid bones and mucosa from 180 patients with CRS after endoscopic sinus
      surgery were collected for histopathologic detection with HE staining. The number
      and the rate of cases were counted according to different histopathologic types.
      To analyze the correlation between ethmoid bones and clinical types of CRS,
      mucosal pathologic change, the CT-scanning types of sinusitis, the course of
      disease as well as operational history. RESULT: The ethmoid bone of all patients
      had varying degrees of histopathologic changes. There were 5 cases (2.78%) in
      stage I, 38 cases (21.11%) in stage II, 71 cases (39.44%) in stage III, and 66
      cases (36.67%) in stage NIV. The histopathologic changes of ethmoid bone varied
      in different clinical types. In type I, there were 5 cases (8.33%) in stage I, 33
      cases (55.00%) in stage II, 15 cases (25.00%) in stage III, and 7 cases (11.67%)
      in stage NV. In type I, there were 5 cases (8.33%) in stage II, 37 cases (61.67%)
      in stage mI, and 18 cases (30.00%) in stage NV. In type III, there were 19 cases
      (31.67%) in stage III, and 41 cases (68.33%) in stage NV. All histopathologic
      changes of ethmoid bone were statistically correlated (P < 0.01) with clinical
      types of CRS, pathologic mucosal change, the CT-scanning types of sinusitis, the
      course of disease as well as operational history. CONCLUSION: Almost all patients
      with CRS manifest different-degrees of histopathologic changes, which are
      correlated with the clinical types of CRS, pathologic mucosal change, the CT
      scanning types, the course of disease as well as operational history.

PMID- 22384564
TI  - [A cohort investigation of the allergen and pathogenesis in the patients with
      allergic rhinitis from three hospital of Guangdong Province].
AB  - OBJECTIVE: To study the pathogenesis of the patients with allergic rhinitis
      diagnosed by Skin Prick Test (SPT), especially about the epidemiologic data of
      the involved allergens. METHOD: The data was collected from 958 patients referred
      to the listed three allergy center and subsequently diagnosed as allergic
      rhinitis by SPT. RESULT: The intermittent mild type was more prevalent in male
      patients (40.5%); comparably the intermittent moderate type in female patients
      (70.0%); in the infant patients the moderate-severe type dominated (73.7%). The
      positive results of SPT comprised mainly of Dermatophagoides pteronyssinus (Der.
      p, 98.3%), Dermatophagoides farinae(Der. f, 96.8%), and Blomia tropicalis (Blot,
      73.8%). Only 1.7% of the patients was allergic to single allergen, in contrary
      ,the majority of patients were allergic to multiple allergens. The positive rate
      to Der. p and Der. f was reversely increasing with age of the patients; and
      contrarily the number of positive allergens was increasing along with the age of
      the patients. The allergy to outdoor allergen was less common, and the positive
      rate in skin prick test was lower than the previously reported rate in North
      China ,such as timothy (3.9%), birch (2.7%), ragweed (2.0%), and mugwort (1.2%).
      CONCLUSION: Dust Mite is the predominant allergen for patients with allergic
      rhinitis in Guangdong province; and the positive rate to outdoor allergen is
      lower than that in North China.

PMID- 22384565
TI  - [Effect of nasal septal suture versus nasal packing after septoplasty].
AB  - OBJECTIVE: Patients undergone septoplasty, which is one of the most common
      procedures, always feel very painful after surgery because of routine nasal
      packing. The objective of this study was to evaluate the effect of septal suture
      technique without nasal packing after septoplasty. METHOD: Eighty patients who
      had undergone septoplasty were included in this study. The patients were
      allocated into tow groups: packing group, mercel was used for nasal packing after
      septoplasty and inferior turbinate coblation; suturing group, septal suture and
      inferior turbinate coblation were performed after septoplasty without nasal
      packing. Postoperative signs and symptoms(visual analogue scale,VAS) were
      compared between the two groups. RESULT: The patients of packing group
      experienced significantly more postoperative nasal pain, headache, dysphagia,
      sleep disturbance and bleeding after surgery (P < 0.01). No difference of
      epiphora was found between the two groups. More pain and bleeding were
      experienced during the pack removal(packing group), compared to that during the
      clearance of nasal cavity (suturing group ). One patient with postoperative
      septal hematoma was found in the packing group. CONCLUSION: Nasal septum suture
      combined with inferior turbinate coblation might be a significantly more
      comfortable, reliable alternative to nasal packing. Nasal packing is not the
      necessary application for septoplasty.

PMID- 22384566
TI  - [Analysis of the clinical and pathological characteristics of sinonasal
      neoplasms].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      sinonasal neoplasms. METHOD: A cohort of 333 patients with sinonasal neoplasm,
      which were confirmed by surgical pathology, were enrolled in this study. The
      clinicopathological characteristics, in terms of age, sex, location, and disease
      constituent ratio were retrospectively reviewed. RESULT: (1) In this series of
      patients, there were 200 males and 133 females, aged from 2 to 84 years, with a
      median of 54 years. The benign to malignant ratio was 1.1:1. As for their
      origination, 144 tumors arose from the nasal cavity, while, 191 tumors derived
      from sinus, including 90 from maxillary sinus, 31 from frontal sinus, 46 from
      ethmoid sinus, and 24 from sphenoidal sinus. (2) Disease constituent ratio
      decreased in order of epithelial tissue, soft tissue, lymphohematopoietic tissue,
      bone and cartilaginous tissue, ectopic intracranial tumors. The five most
      frequent malignant tumors were squamous carcinoma, lymphoma, adenoid cystic
      carcinoma, malignant melanoma and esthesioneuroblastoma, while, benign tumors
      ranked in the top five were papilloma, fibroma, osteoma, angioma and ectopic
      intracranial tumors,respectively. (3) Of 200 cases arising from epithelium, 118
      were benign, 82 were malignant, and the benign to malignant ratio was 1.4:1. Of
      68 cases from soft tissue, 37 were benign and 31 were malignant tumors (ratio,
      1.2:1). Among the 22 cases from bone and cartilaginous tissue, 17 were benign and
      5 were malignant (ratio, 3.4:1). With respect to the 29 cases from
      lymphohematopoietic tissue, the majority of tumors were malignant (28 cases),
      with only one benign case. In addition, ectopic intracranial tumors were also
      observed. Besides the above all, 12 cases of other types were found in this work.
      CONCLUSION: Neoplasms from different parts of nasal cavity and paranasal sinus
      have specific clinical characteristics. The pathological types of these tumors
      may be highly diverged. The diagnosis and differential diagnosis depend mainly on
      pathological examination. Comprehensive treatment, which employs surgery in
      combination with other modalities, is the main strategy for these tumors.

PMID- 22384568
TI  - [Radiological research of maxillary sinus development of children and adolescent
      without sinusitis in Kunming of Yunnan].
AB  - OBJECTIVE: To investigate the maxillary sinus development and provide data for
      sinus surgery on children. METHOD: Two thousand two hundred and thirty-eight
      children were randomly selected among those who underwent skull and nasal sinus
      CT scanning because of certain symptoms and signs. Patients were divided into
      eighteen age cohorts based on their age at the time of the scan. Anterior
      posterior, transverse diameters and vertical height of the maxillary sinus were
      measured and statistically analyzed. RESULT: The maxillary sinus volume was
      enlarging even in adult, hut the growth of maxillary sinus was relatively stable
      in adolescent. The difference of transverse and anterior-posterior diameters of
      maxillary sinus had no statistical significance between female and male (P >
      0.05), while there was statistically significant difference in the vertical
      height of maxillary sinus (P < 0.05). CONCLUSION: The results will aid the
      physicians when correlating the clinical and radiographic findings of pediatric
      patients who are being evaluated for sinus disease and potential surgical
      intervention.

PMID- 22384567
TI  - [Study on the relationship between SNP of CD14 gene and allergic rhinitis in
      Xinjiang Uygurs and Hans].
AB  - OBJECTIVE: This study aimed to investigate the relationship between CD14 gene
      rs2569192(C/G), rs3138078 (--1359G/T) and allergic rhinitis (AR) in Xinjiang
      Uygur and Han populations as well as to determine characteristics of
      polymorphisms. METHOD: A total of 300 AR and 300 healthy controls subjects were
      included. The frequencies of genotypes and alleles were detected as well as the
      levels of tIgE in different genotypes were compared. RESULT: (1) The distribution
      of genotypes or alleles of CD14 gene rs2569192 (C/G), rs3138078 (--1359G/T) had
      no differences between the Xinjiang Uygurs and Hans (P > 0.05). The highest
      frequency of alleles was C, G. (2) The frequencies of genotypes and alleles were
      not different between the AR and control group in Uygur and Han (P > 0.05). The
      frequencies of genotypes and alleles of rs2569192 were different between the
      Uygur AR and Han AR group (P < 0.05). (3) The distribution of genotype
      frequencies and allele of rs 2569192 in the Xinjiang Uygur and Han population
      were quite different from Chinese Beijing Han populations, Japanese, European and
      African (P < 0.05). (4) The serum total IgE level in AR group was higher than
      that in healthy control group (P < 0.05). CONCLUSION: (1) rs2569192 (C/G),
      rs3138078 (--1359G/T) polymorphisms were not different between the Chinese
      Xinjiang Uygur and Han population. The major allele were both C and G. rs2569192
      of CD14 in Xinjiang populations was different from that in the other populations.
      (2) No relationship between rs2569192, rs3138078 and AR was found. (3) The serum
      total IgE level in AR group was higher than that in healthy control group. No
      relationship between CD14 two SNP and serum total IgE level was found.

PMID- 22384569
TI  - [Clinical analysis of 111 patients with non-invasive fungal rhino-sinusitis].
AB  - OBJECTIVE: To analyze the clinical characteristics, diagnosis and treatment
      course and clinical effect of non-invasive fungal rhino-sinusitis, and to
      investigate the diagnostic and treating methods and factors affecting the
      clinical outcome. METHOD: A retrospective study was conducted on 111 patients who
      were diagnosed with noninvasive fungal rhino-sinusitis from 2005 to 2009 in our
      department. Clinical symptoms, endoscopic and CT examinations, surgical methods,
      surgical outcomes and the treatment of the recurrent cases were reviewed. RESULT:
      Eighty-six cases were reassured of the non-invasive fungal rhino-sinusitis by
      means of clinical symptoms, endoscopic and CT examinations. All the patients who
      underwent functional endoscopic sinus surgery showed satisfying clinical effect
      and no complications occurred. During the follow-up, recurrence was found in 12
      cases 1 to 5 years postoperatively, and 7 were cured after medication and
      debridement under endoscope in outpatient department while the clinical outcome
      of the other 5 was unsatisfactory. CONCLUSION: Non-invasive fungal rhino
      sinusitis is distinctive in endoscopic and CT examination which is different from
      common chronic rhino-sinusitis, and endoscopic sinus surgery is an effective
      treatment for the disease. Radical debridement and successful drainage of the
      nasal sinus is the key factor affecting the effect of the treatment and clinical
      outcome.

PMID- 22384570
TI  - [Preliminary clinical investigation of coblation-assisted functional endoscopic
      sinus surgery for chronic sinusitis and nasal polyps].
AB  - OBJECTIVE: To explore the clinical efficacy of coblation-assisted FESS (CAFESS)
      by observing the patients intraoperatively and postoperatively. METHOD: Thirty
      patients with chronic sinusitis or/and with nasal polyps were selected. The
      subjective symptoms and objective changes were observed 6 to 9 months after
      CAFESS. RESULT: The sense of nasal congestion, headache and face pain, purulent
      rhinorrhea, postnasal drip, and other symptoms were relieved. The scores of SNOT
      20 reduced from preoperative (22.53 +/- 6.26) to (7.80 +/- 3.63) 6 months
      postoperatively, and the difference was statistically significant (t = 16.741, P
      < 0.05). The scores of Lund-Kennedy decreased from (4.30 +/- 1.15) preoperatively
      to (1.17 +/- 0.83) 6 months postoperatively, and the difference was statistically
      significant (t = 19.947, P < 0.05). The observation under endoscope illustrated
      that epithelization commenced at 6w postoperatively and completed until 12 week
      after CAFESS. CONCLUSION: CAFESS is a new technique for treatment of chronic
      sinusitis and nasal polyps, and postoperative clinical results were satisfactory.
      It's a good method for the treatment of chronic sinusitis and nasal polyps.

PMID- 22384571
TI  - [Expression of transcription factors T-bet and GATA-3 and relationship to the
      numbers of eosinophils in rat model of allergic rhinitis].
AB  - OBJECTIVE: To explore the expression of T-bet/GATA-3 in nasal mucosa tissue of
      allergic rhinitis rat and to investigate the association between the expression
      of T-bet/GATA-3 and the eosinophil count. METHOD: Twenty SD rats were randomly
      divided into a control group and an allergic rhinitis group. The allergic
      rhinitis rat model was induced with ovalbumin. The total eosinophils were counted
      in the nasal mucosa. The concentrations of IL-4, IL-5 and IFN-gamma in nasal
      lavage fluid were measured by ELISA. The mRNA and protein expressions of IL-4, IL
      5, IFN-gamma, T-bet and GATA-3 in the nasal mucosa were detected by RT-PCR and
      Western blot respectively. RESULT: The main inflammatory cells were eosinophils
      in the nasal mucosa of allergic rhinitis rats. The level of IL-4, IL-5 and IFN
      gamma in control group was significantly higher than that in allergic rhinitis
      group (P < 0.01). The mRNA and protein expression of IFN-gamma and T-bet in
      allergic rhinitis group was significantly higher than that in control group (P <
      0.01). While the mRNA and protein expression of IL-4, IL-5 and GATA-3 in control
      group was significantly higher than that in allergic rhinitis group (P < 0.01).
      The ratio of protein expression of T-bet and GATA-3 was negatively correlated
      with the eosinophil count, IL-4 and IL-5, but positively with the concentrations
      of IFN-gamma. CONCLUSION: The imbalance of transcription factor GATA-3 and T-bet
      has a close correlation with the eosinophil count, and may play a key role in the
      formation of allergic rhinitis.

PMID- 22384572
TI  - [Effects of litter and mineral nitrogen input on soil organic carbon
      decomposition in subtropical mixed forest in Dinghu Mountain, South China].
AB  - In July-December 2010, a complete factor-controlled experiment was conducted to
      study the effects of litter and mineral nitrogen addition on soil organic matter
      decomposition (soil respiration) at the depths of 0-10 cm and 20-30 cm in Dinghu
      Mountain National Reserve. Coniferous needle litter and broadleaved litter were
      added, respectively, and 70 g N x m(-2) x yr(-1) of NH4 NO3 was applied to
      simulate soil nitrogen saturation whereas soil mineral nitrogen was removed by
      ion-exchange membrane to simulate the decreased nitrogen absorption by root. The
      addition of both needle litter and broadleaved litter increased the respiration
      rate of soil-litter system significantly from July to November, but this effect
      disappeared in December. Both mineral nitrogen application and soil mineral
      nitrogen removal increased the soil-litter respiration significantly. These
      results suggest that litter decomposed completely in a short period therefor had
      limited effects on soil organic matter decomposition and accumulation, and thus,
      foliar litters could be not the major source of soil organic matter, whereas soil
      mineral nitrogen removal could obviously promote the soil organic matter
      decomposition in the system.

PMID- 22384573
TI  - [Characteristics of foliar delta13C values of common shrub species in various
      microhabitats with different karst rocky desertification degrees].
AB  - By measuring the foliar delta13C values of 5 common shrub species (Rhamnus
      davurica, Pyracantha fortuneana, Rubus biflorus, Zanthoxylum planispinum, and
      Viburnum utile) growing in various microhabitats in Wangjiazhai catchment, a
      typical karst desertification area in Guizhou Province, this paper studied the
      spatial heterogeneity of plant water use at niche scale and the response of the
      heterogeneity to different karst rocky desertification degrees. The foliar
      delta13C values of the shrub species in the microhabitats followed the order of
      stony surface > stony gully > stony crevice > soil surface, and those of the
      majority of the species were more negative in the microhabitat soil surface than
      in the others. The foliar delta13C values decreased in the sequence of V. utile >
      R. biflorus > Z. planispinum > P. fortuneana > R. davurica, and the mean foliar
      delta13C value of the shrubs and that of typical species in various microhabitats
      all increased with increasing karst rocky desertification degree, differed
      significantly among different microhabitats. It was suggested that with the
      increasing degree of karst rocky desertification, the structure and functions of
      karst habitats were impaired, microhabitats differentiated gradually, and drought
      degree increased.

PMID- 22384574
TI  - [Responses of Pinus sylvestris var. mongolica radial growth to climate warming in
      Great Xing' an Mountins: a case study in Mangui].
AB  - Based on the theory and methodology of dendrochronology, the tree ring width
      chronology of Pinus sylvestris var. mongolica in Mangui of Great Xing' an
      Mountains was developed, and the relationships between the standardized tree ring
      width chronology and local climate factors (temperature and precipitation) as
      well as the effects of climate factors on the P. sylvestris var. mongolica radial
      growth were analyzed. In this region, the mean monthly temperature in April
      August of current year was the main factor limiting the radial growth, and the
      increasing mean monthly temperature from April to August had negative effects to
      the radial growth. The simulation of the variations of the radial growth by the
      mean monthly temperature change in April-August showed that the radial growth of
      P. sylvestris var. mongolica would present a declining trend accompanied with the
      warmer and drier regional climate condition.

PMID- 22384575
TI  - [Complexity and its integrative effects of the time lags of environment factors
      affecting Larix gmelinii stem sap flow].
AB  - Based on the one-year (2005) observations with a frequency of half hour on the
      stem sap flow of Larix gmelinii plantation trees planted in 1969 and the related
      environmental factors air humidity (RH), air temperature (T(air)), photosynthetic
      components active radiation (PAR), soil temperature (T(soil)), and soil moisture
      (TDR), principal analysis (PCA) and correction analysis were made on the time lag
      effect of the stem flow in different seasons (26 days of each season) and in a
      year via dislocation analysis, with the complexity and its integrative effects of
      the time lags of environment factors affecting the stem sap flow approached. The
      results showed that in different seasons and for different environmental factors,
      the time lag effect varied obviously. In general, the time lag of PAR was 0.5-1
      hour ahead of sap flow, that of T(air) and RH was 0-2 hours ahead of or behind
      the sap flow, and the time lags of T(soil) and TDR were much longer or sometimes
      undetectable. Because of the complexity of the time lags, no evident improvements
      were observed in the linear correlations (R2, slope, and intercept) when the time
      lags based on short-term (20 days) data were used to correct the time lags based
      on whole year data. However, obvious improvements were found in the standardized
      and non-standardized correlation coefficients in stepwise multiple regressions,
      i.e., the time lag corrections could improve the effects of RH, but decreased the
      effects of PAR, T(air), and T(soil). PCA could be used to simplify the
      complexity. The first and the second principal components could stand for over
      75% information of all the environmental factors in different seasons and in
      whole year. The time lags of both the first and the second principal components
      were 1-1.5 hours in advance of the sap flow, except in winter (no time lag
      effect).

PMID- 22384576
TI  - [Effects of eutrophic nitrogen nutrition on carbon balance capacity of
      Liquidambar formosana seedlings under low light].
AB  - To investigate the effects of atmospheric nitrogen deposition on the seedlings
      regeneration of Liquidambar formosana, a greenhouse experiment was conducted, in
      which, the low light- and nitrogen supplies were controlled similar to those in
      typical L. formosana secondary forests, with the effects of different light- and
      nitrogen supply on the L. formosana seedlings survival, leaf functional traits,
      biomass allocation, and gas exchange studied. The whole plant light compensation
      point (LCP(whoIe-plant)) of the seedlings was estimated with a whole plant carbon
      balance model, and then compared with the understory photosynthetic active
      radiance (PAR) of the typical secondary forests. Under 3.0% and 6.0% of full
      sunlight, eutrophic nitrogen supply led to a decrease of seedlings survival
      (shade tolerance) and specific leaf area (SLA), but had no obvious effects on the
      seedlings biomass allocation. At eutrophic nitrogen supply, light intensity had
      significant effects on the leaf area based maximum assimilation rate, whereas
      increasing nitrogen supply under low light induced the increase of leaf mass
      based dark respiration rate. Both light intensity and nitrogen supply had
      significant effects on the mass based leaf respiration rate, and the interaction
      of light and nitrogen had significant effects on the mass based stem respiration
      rate. Increasing nitrogen supply increased the LCP(wholeplant), under 3.0%, 6.0%,
      and 12.0% of full sunlight, but decreased the LCP(whoIe-plant) under 25.0% of
      full sunlight. The decrease of the seedlings shade tolerance induced by the
      increasing nitrogen supply under low light was correlated with the variations of
      the seedlings carbon balance capacity. Under the background of elevated
      atmospheric nitrogen deposition, the maintenance of L. formosana populations in
      China would more depend on disturbances and gap regeneration, and the population
      dynamics would be deeply affected.

PMID- 22384577
TI  - [Regeneration characteristics of woody plant seedlings in typical secondary
      forests in Qinling Mountains].
AB  - By using sampling plot method, an investigation was conducted on the regeneration
      characteristics of woody plant seedlings in five kinds of typical secondary
      forests (Pinus tabulaeformis, Quercus valiena var. acuteserrata, Betula albo
      sinensis, Picea asperata, and Pinus armandii) in Qinling Mountains. There was an
      obvious species differentiation of woody plant seedlings and saplings in the
      forests. Except for Q. valiena var. acuteserrata and P. armandii forests, the
      similarity coefficient of the seedlings and saplings species in the forests was
      lower. The seedlings and saplings quantity, species richness index, Simpson
      dominance index, and evenness index were higher in P. tabulaeformis and Q.
      valiena var. acuteserrata forests, the lowest in B. albo-sinensis forest, and
      basically the same in P. asperata and P. armandii forests. The percentages of the
      seedlings and saplings in the five forests had significant differences (P <
      0.05). Except in B. albo-sinensis forest where the percentage of the saplings was
      higher, the percentage of the seedlings in the other stands was larger, and in
      the order of P. asperata forest > P. tabulaeformis forest > Q. valiena var.
      acuteserrata forest > P. armandii forest, respectively. The sprouting percentage
      of the seedlings in different forests had significant difference (P < 0.05), and
      was in the sequence of P. armandii forest > P. asperata forest > B. albo-sinensis
      forest > Q. valiena var. acuteserrata forest > P. tabulaeformis forest. In Q.
      valiena var. acuteserrata and P. tabulaeformis forests, the percentage of tree
      seedlings was the highest, occupying 68% and 51.4% of the total number of woody
      seedlings, respectively, and their communities were in the medium succession
      period, with a stronger persistent regeneration capability; in P. asperata and P.
      armandii forests, the percentage of tree seedlings was 40% and 15%, respectively,
      and their communities were in the late succession period, with a rather poor
      regeneration capability; while in B. albo-sinensis forest, the seedlings were
      difficult to develop into saplings, and thus, its continuous persistent
      regeneration capability was lack.

PMID- 22384578
TI  - [Effects of fertilization on arbuscular mycorrhizal fungi in Elymus nutans
      roots].
AB  - By using traditional staining and DNA cloning and sequencing techniques, this
      paper studied the effects of fertilization on the arbuscular mycorrhizal (AM)
      colonization and AM fungal community in Elymus nutans roots across an 8-year
      nitrogen (N) and phosphorus (P) fertilization gradient. With the increasing level
      of fertilization, the AM colonization and arbuscular colonization per unit root
      length reduced from 67.5% to 7.3% and from 5.2% to 0.1%, respectively. A total of
      24 AM fungal phylotypes were detected in E. nutans roots, whilst the mean AM
      fungal richness reduced from 6 to 2.6 across the fertilization gradient.
      Different fertilization had significant effects on the AM fungal community
      composition, and there existed significant correlations between the AM fungal
      community composition and the soil available P and root N contents. The
      availability of N and P increased gradually across the fertilization gradient,
      and had significant negative correlations with both AM colonization and AM fungal
      richness. It was suggested that high level fertilization would reduce the
      activity of AM symbionts, and result in the large loss of AM fungal biodiversity.

PMID- 22384579
TI  - [Interspecific allelopathic effect of different organs' aqueous extracts of
      Betula platyphylla and Larix olgensis on their seed germination and seedling
      growth].
AB  - In this paper, the Betula platyphylla root-, branch-, and foliage aqueous
      extracts and Larix olgensis root-, branch-, foliage-, and bark aqueous extracts
      over a range of concentrations 5.0, 12.5, 25.0, 50.0, and 100.0 mg x mL(-1) were
      used to study their interspecific allelopathic effect on the seed germination and
      seedling growth of the two tree species. All the L. olgensis organs' extracts,
      except its root extracts at concentration 5.0 mg x mL(-1), had inhibition effect
      on B. platyphylla seed germination rate, which was 54%, 58%, 59%, and 66% under
      the effects of L. olgensis foliage-, branch-, bark-, and root extracts,
      respectively, as compared with the control. With increasing concentration, the
      inhibition effect of L. olgensis root- and branch extracts increased while that
      of L. olgensis foliage- and bark extracts decreased. The L. olgensis organs'
      extracts, especially the foliage extracts at concentration 100.0 mg x mL(-1), had
      strong inhibition effect on B. platyphylla seed radicle- and hypocotyl length
      growth, with a decrement of 38% and 55% (P < 0.05), respectively. L. olgensis
      branch- and foliage extracts promoted, but root- and bark extracts inhibited B.
      platyphylla seedling growth and biomass production. B. platyphylla organs'
      extracts promoted L. olgensis seed germination, root- and branch extracts
      promoted hypocotyl length growth, but foliage extracts at 50.0 and 100.0 mg x mL(
      1) decreased the hypocotyl length growth by 27% and 28% (P < 0.05), respectively.
      B. platyphylla organs' extracts mainly promoted L. olgensis seedling growth, with
      the height- and collar diameter growth and biomass accumulation at B. platyphylla
      foliage extracts concentration 5.0 mg x mL(-1) increased by 54%, 60%, and 100% (P
      < 0.05), respectively. Our results suggested that there existed obvious
      allelopathic effect between B. platyphylla and L. olgensis, and thus, mixed
      planting B. platyphylla and L. olgensis could have promotion effects on the
      growth of the two tree species.

PMID- 22384580
TI  - [Changes of plant community biomass and soil nutrients during the vegetation
      succession on abandoned cultivated land in desert steppe region].
AB  - By the method of substituting temporal serial with spatial serial, and taking
      five abandoned cultivated lands with different ages (1, 4, 9, 12, and 20 years)
      in desert steppe region as test objects, this paper studied the change
      characteristics of plant community biomass and soil nutrients during vegetation
      succession. With the increasing abandoned years, the plant community aboveground
      biomass on the abandoned lands increased after an initial decrease, whereas the
      total nitrogen, total phosphorus, organic carbon contents, and carbon density in
      0-60 cm soil layer increased first, decreased then, and increased again, with the
      maximum values of soil total nitrogen and phosphorus contents appeared on the
      abandoned lands with the ages 4 and 20 years. During vegetation succession, the
      effects of soil total nitrogen and organic carbon on plant community biomass were
      greater than those of soil total phosphorus and soil bulk density.

PMID- 22384581
TI  - [Effects of exogenous abscisic acid (ABA) on the photosynthesis and chlorophyll
      fluorescence parameters of Tripterygium wilfordii seedlings exposed to low
      temperature].
AB  - Taking one year-old Tripterygium wilfordii cutting seedlings as test materials,
      this paper studied the effects of foliar spraying 0, 5, 10, 15, 20, and 25 mg x
      L(-1) of abscisic acid (ABA) on the leaf photosynthesis and chlorophyll
      fluorescence characteristics of the seedlings under low temperature stress.
      Spraying 20 mg x L(-1) of ABA increased the cold- resistance of the seedlings
      significantly, manifesting in the slowing down of the decrease amplitudes of leaf
      net photosynthetic rate (P(n)), transpiration rate (T(r)), stomatal conductance
      (g(s)), and intercellular CO2 concentration (C(i)) and the increase of
      photosynthetic capacity. After 6 days exposure to low temperature, the initial
      fluorescence (F(o)) decreased with increasing concentration of applied ABA, the
      maximum fluorescence (F(m)) and maximal photochemical yield (F(v)/F(m))
      increased, the actual photochemical efficiency of system II (phi(PSII)) and
      photochemical quenching coefficient (q(P)) increased after an initial decrease,
      and the non-photochemical quenching coefficient (q(N)) showed a 'decreasing
      increasing-decreasing' trend. The P(n), g(s), q(P), F(m), and F(v)/F(m) reached
      their peak values at 20 mg x L(-1) of ABA. In all treatments, with the increase
      of photosynthetically active radiation (PAR), the relative electron transport
      rate (rETR) increased first and decreased then, reached the peak when the PAR was
      395 micromol x m(-2) x s(-1), and the peak value of the rETR in treatments 25 and
      20 mg x L(-1) of ABA was 17.1% and 5.2% higher than that of the control,
      respectively. The light response curves of the psi(PSII) decreased with
      increasing PAR, whereas those of q(N) performed in adverse.

PMID- 22384582
TI  - [Effects of foliar spraying methyl jasmonate on leaf chlorophyll fluorescence
      characteristics of flue-cured tobacco seedlings under drought and re-watering].
AB  - Taking the flue-cured tobacco variety of "Longjiang 911" from Heilongjiang
      Province of Northeast China as test material, a pot experiment was conducted to
      study the effects of foliar spraying different concentration methyl jasmonate
      (MeJA) on the seedlings leaf chlorophyll content and chlorophyll fluorescence
      characteristics during the transplantation stage under drought and re-watering.
      Under drought condition, the leaf chlorophyll content, maximum fluorescence
      (F(m)), potential activities of PSII (F(v)/F(o)), maximum photochemical
      efficiency (F(v)/F(m)), actual photochemical efficiency (psi(PSII)), apparent
      electron transport rate (ETR), and photochemical quenching (q(P)) decreased, but
      the minimal fluorescence (F(o)) and non-photochemical quenching (q(N)) increased.
      Foliar spraying 0.2 and 0.5 mmol x L(-1) of MeJA had obvious positive effects in
      mitigating the decrease of F(v)/F(m), F(v)/F(o), phi(PSII), ETR, and q(P) and the
      increase of q(N) under drought stress, while spraying 1.0 mmol x L(-1) of MeJA
      had lesser effects. After re-watering, all the leaf chlorophyll fluorescence
      indices had obvious recovery, and spraying MeJA made the indices more close to
      the original levels before drought. It was suggested that foliar spraying MeJA
      could alleviate the degradation of chlorophyll and play definite role in
      protecting the PSII under drought stress, decrease the damage of drought stress
      on the seedlings, promote the rapid MeJA recovery of chlorophyll fluorescence
      parameters after re-watering, and thus, ensure the regrowth of flue-cured tobacco
      seedlings.

PMID- 22384583
TI  - [Soil nutrient distribution and its relations with topography in Huangshui River
      drainage basin].
AB  - By using GIS and geostatistic techniques, this paper studied the spatial
      distribution patterns of soil nutrients and their relationships with topographic
      factors in Huangshui River drainage basin, a water source of Danjiangkou
      Reservoir. In the study area, the soil total nitrogen, total phosphorus, and
      organic matter varied spatially at medium level, with the variation coefficients
      being 51%, 66%, and 85%, respectively, whereas the soil available phosphorus
      displayed a strong spatial variation, with the variation coefficient reached
      161%. The soil total nitrogen and organic matter exhibited a spatially positive
      autocorrelation, while the soil total and available phosphorus presented a
      spatially weak autocorrelation. Altitude was one of the main topographic factors
      affecting the spatial distribution patterns of the soil nutrients, having
      significant effects on the spatial distribution of total nitrogen, total
      phosphorus, and organic matter. Slope and profile curvature also had significant
      effects on the spatial distribution of the soil total nitrogen and organic
      matter. Based on these, the regression prediction models of topographic factors
      and soil nutrient spatial distribution were established, and the digital mappings
      of the soil nutrients were made, which provided data support for the precise
      management of soil resources in the study area.

PMID- 22384584
TI  - [Evaluation of soil quality under different land use types in Naban River
      watershed, Yunnan Province of Southwest China].
AB  - Eighty-six topsoil (0-20 cm) samples were collected from 8 land use types
      (natural forest land, maize field, tea garden, paddy field, rubber plantation,
      flax field, banana plantation, and sugarcane field) in the Naban River Watershed
      National Nature Reserve and its surrounding areas, and the soil physical and
      chemical properties were analyzed, aimed to study the effects of land use type on
      the soil quality by the method of soil quality index (SQI). Comparing with
      natural forest land, all the cultivated lands had somewhat decreased soil organic
      matter content and higher soil bulk density, and the soil bulk density was
      significantly higher in tea garden, paddy field, rubber plantation, and banana
      plantation. In cultivated lands, fertilization and reclamation made the soil
      available potassium and phosphorus contents maintained at a higher level,
      probably due to the input of mineral potassium and phosphorus and the
      decomposition of soil organic matter. The SQI of the 8 land use types was in the
      order of flax field (0.595) > natural forest land (0.532) > maize field (0.516) >
      banana plantation (0.485) tea garden (0.480) sugarcane field (0.463) > paddy
      field (0.416) > rubber plantation (0.362). The soils in higher altitude
      production demonstration areas (1614 +/-115 m) had significant higher SQI,
      compared to the soils in lower altitude buffer areas (908 +/- 98 m) and junction
      areas (926 +/- 131 m). Among the 8 land use types, the rubber plantation in lower
      altitude areas had the lowest SQI, due to the lower soil organic matter and
      available potassium and phosphorus contents and the highest soil bulk density.
      Application of organic manure or intercropping with leguminous plants could be an
      available practice to improve the soil quality of the rubber plantation.

PMID- 22384585
TI  - [Changes of China agricultural climate resources under the background of climate
      change: IX. Spatiotemporal change characteristics of China agricultural climate
      resources].
AB  - Based on the 1961-2007 ground surface meteorological data from 558 meteorological
      stations in China, this paper analyzed the differences of agricultural climate
      resources in China different regions, and compared the change characteristics of
      the agricultural climate resources in 1961-1980 (period I) and 1981-2007 (period
      II), taking the year 1981 as the time node. As compared with period I, the mean
      annual temperature in China in period II increased by 0.6 degrees C, and the > or
      = 0 degrees C active accumulated temperature in the growth periods of
      chimonophilous crops and the > or = 10 degrees C active accumulated temperature
      in the growth periods of thermophilic crops increased averagely by 123.3 degrees
      C x d and 125.9 degrees C x d, respectively. In 1961-2007, the mean annual
      temperature increased most in Northeast China, and the > or = 10 degrees C active
      accumulated temperature in the growth periods of thermophilic crops increased
      most in South China. The whole year sunshine hours and the sunshine hours in the
      growth periods of chimonophilous crops and of thermophilic crops in period II
      decreased by 125.7 h, 32.2 h, and 53.6 h, respectively, compared with those in
      period I. In 1961-2007, the annual sunshine hours decreased most in the middle
      and lower reaches of Yangtze River, while the sunshine hours in the growth
      periods of chimonophilous crops and of thermophilic crops decreased most in North
      China and South China, respectively. In the whole year and in the growth periods
      of chimonophilous and thermophilic crops, both the precipitation and the
      reference crop evapotranspiration in this country all showed a decreasing trend,
      with the largest decrement in the precipitation in the whole year and in the
      growth periods of chimonophilous and thermophilic crops in North China, the
      largest decrement in the reference crop evapotranspiration in the whole year and
      in the growth periods of thermophilic crops in the middle and lower reaches of
      Yangtze River, and the largest decrement in the reference crop evapotranspiration
      in the growth periods of chimonophilous crops in Northwest China. In 1961-2007,
      the climate in China in the whole year and in the growth periods of thermophilic
      crops showed an overall tendency of warm and dry, and the climate in the growth
      periods of thermophilic crops became warm and dry in Southwest China, North
      China, and Northeast China, but warm and wet in the middle and lower reaches of
      Yangtze River, Northwest China, and South China, whereas the climate in the
      growth periods of chimonophilous crops became warm and dry in North China, but
      became warm and wet in Northwest China.

PMID- 22384586
TI  - [Climatic potential productivity of winter wheat and summer maize in Huanghuaihai
      Plain in 2011-2050].
AB  - Based on the daily data under B2 climate scenario (2011-2050) and baseline
      climate condition (1961-1990) extracted from the regional climate model PRECIS,
      and by using the Agro-Ecological Zone (AEZ) model, a prediction was conducted on
      the possible spatiotemporal changes of the climatic potential productivity of the
      two crops in the Huanghuaihai Plain in 2011-2050. Under baseline climate
      condition, the climatic potential productivities of winter wheat and summer maize
      presented a regional differentiation, i.e., higher in southeast and lower in
      northwest regions, and higher along coast and lower in inland at the same
      latitudes, and fluctuated within the ranges of 3893-11000 kg x hm(-2) and 5908
      12000 kg x hm(-2), respectively. Under B2 climate scenario, the climatic
      potential productivity of winter wheat and summer maize would have a greater
      inter-annual change, due to the different matching degrees of light, temperature
      and water during the growth periods of the crops. The climatic potential
      productivity of winter wheat in 2011-2030 and summer maize in 2021-2040 would
      have an obvious increase, with great potential for development. Under the
      conditions of maintaining the present production, the climatic potential
      productivity of winter wheat in 2011-2050 would present an overall regional
      differentiation of reverse change in southeast and northwest regions and the same
      change in coastal and inland areas, whereas the climatic potential productivity
      of summer maize in 2011-2050 would have little regional differentiation.

PMID- 22384587
TI  - [Carbon sequestration effects of rice straw return in double season paddy field
      in Southern China].
AB  - In a long-term site-specific experiment with rice straw return (RSR) and in a
      short-term experiment with different RSR modes, this paper studied the effects of
      RSR on the soil organic carbon (SOC) sequestration, methane emission, and net
      carbon sink in a double season paddy field. RSR increased the SOC content, and
      the annual increasing rate of soil carbon sink in plow layer (0-15 cm) under long
      term RSR was 0.07 t C x hm(-2) x a(-1). With the increasing amount of RSR, the
      apparent SOC transformation rate decreased. RSR promoted the methane emission
      from the paddy field significantly, and the methane emission flux in treatment
      RSR plus NPK during early- and late rice growth seasons increased by 75.0% and
      251.5% (P < 0.01), respectively, compared with that in treatment NPK. The methane
      emission increased with the increasing amount of RSR. Under the similar tillage
      mode and rice yield, the rice straw returned had the similar apparent methane
      transformation rate. Considering the soil carbon sequestration and the net carbon
      sink after methane emission in the paddy field comprehensively, treatment RSR
      plus NPK had significant negative effect on the carbon sink which was basically
      approached to the bio-fixation of carbon by rice and increased by 158.3%, as
      compared with treatment NPK. Among different RSR modes, rice straw mulching plus
      no tillage decreased soil methane emission significantly, with the net carbon
      sink decreased by 50.9% as compared with the treatment high stubble plus tillage,
      and benefited the high and stable yielding of rice.

PMID- 22384588
TI  - [Effects of irrigation amount and frequency on soil water distribution and water
      use efficiency in a cotton field under mulched drip irrigation].
AB  - A 2-year (2009 and 2010) field experiment was carried out to investigate the
      effects of irrigation amount (300, 375, and 450 mm) and irrigation frequency
      (once every 3-, 7-, and 10 days) on the soil water distribution and cotton water
      use efficiency (WUE) under mulched drip irrigation in North Xinjiang. When the
      irrigation amount was 375 mm, irrigation once every 3 days induced a higher water
      content in surface soil (0-20 cm) in the whole growth season of cotton but made
      the deeper (below 40 cm) soil not moistened enough. Irrigation once every 10 days
      benefited the irrigation water penetrated downward or sideways and made the
      deeper soil have a higher water content; however, this drip irrigation did not
      replenish water in time, and made the surface soil water content lower. Overall,
      drip irrigation once every 7 days benefited the uniform distribution of
      irrigation water in soil profile. Under the same irrigation frequencies, the
      larger the irrigation amount, the higher the soil water content. The cotton water
      consumption in all treatments had the similar pattern, i. e., lower at seedling
      stage (averagely < 1.7 mm x d(-1)), increased gradually since squaring stage and
      reached the maximum at full bloom stage (about 8.7 mm x d(-1)), and decreased at
      onen-boll staue (about 1.0 mm x d(-1). Under the natural condition, the total
      cotton water consumption had close correlation with irrigation amount but poor
      correlation with irrigation frequency, and the cotton WUE decreased significantly
      with increasing irrigation amount. When the irrigation amount was 300 mm, the WUE
      was higher but the yield production decreased markedly, whereas excessive
      irrigation (450 mm) had no significant yield-increasing effect but wasted water.
      It was suggested that irrigation with an amount of 375 mm and a frequency of once
      every 7- or 10 days could be an appropriate drip irrigation mode for the local
      cotton field under natural condition.

PMID- 22384589
TI  - [Characteristics of nitrogen and phosphorus runoff losses from croplands with
      different planting patterns in a riverine plain area of Zhejiang Province, East
      China].
AB  - By the method of site-specific observation, and selecting 27 field plots with 7
      planting patterns in Shaoxing county of Zhejiang Province as test objects, this
      paper studied the characteristics of nitrogen (N) and phosphorous (P) runoff
      losses, loads, and their affecting factors in the croplands with different
      planting patterns in riverine plain area of the Province under natural rainfall.
      The mean annual runoff loads of total P, dissolved P, and particulate P from the
      field plots were 4.75, 0.74 and 4.01 kg x hm(-2), respectively, and the load of
      particulate P was much higher than that of dissolved P. The mean annual runoff
      loads of total N, dissolved total N, dissolved organic N, NH4(+)-N, and NO3(-)-N
      were 21.87, 17.19, 0.61, 3.63 and 12.95 kg x hm(-2), respectively, and the load
      of different fractions of dissolved total N was in the sequence of NO3(-)-N >
      NH4(+)-N > dissolved organic N. As for the field plots with different planting
      patterns, the runoff loads of total N, dissolved total N, dissolved organic N,
      and NO3(-)-N were in the sequence of fallow land < nursery land < single late
      rice field < double rice field < rape (or wheat)-single late rice field < wheat
      early rice-late rice field < vegetable field, while those of total P and
      particulate P were in the sequence of fallow land < nursery land < single late
      rice field and double rice field < wheat-early rice-late rice field < rape
      (wheat)-single late rice field < vegetable field. No significant difference was
      observed in the load of water-dissolved P among the test plots with different
      planting patterns. The runoff losses of N and P mainly occurred in crop growth
      period, and the proportions of N and P losses in the growth period increased with
      increasing multiple crop index. The runoff losses of total N, dissolved N, and
      NO3(-)-N were mainly related to the application rate of N fertilizer, and soil
      NO3(-)-N content also had obvious effects on the runoff losses of total N and
      dissolved N. The runoff loss of dissolved organic N was related not only to N
      application rate, but also to soil total N and organic carbon. The runoff loss of
      NH4(+)-N was mainly related to soil available NH4(+)-N, but not related to N
      application rate. The runoff losses of total P and particulate P were related to
      both P application rate and soil available P, while the runoff loss of water
      dissolved P was less related to P application rate but had relations to soil
      total P and available P.

PMID- 22384590
TI  - [Effects of returning maize straw into field on the Zn forms and their
      availability in a calcareous soil].
AB  - Maize straws were put into nylon mash bags and buried in a calcareous soil to
      study the effects of returning maize straw into field on the calcareous soil Zn
      forms and their availability. Compared with Zn fertilization, returning maize
      straw into field had little contribution to the soil total Zn content. Both Zn
      fertilization and straw returning increased the soil DTPA-Zn content
      significantly, and the increment was larger under Zn fertilization. As compared
      to that in low Zn concentration straw, the Zn released from high Zn concentration
      straw after returned into soil was more easily transformed into soil DTPA-Zn,
      with the transformation rate reached 49.0%. The transformation rate of soil DTPA
      Zn had a trend of decreasing first and increasing then after straw returned into
      soil, but had little change under Zn fertilization. The soil exchangeable Zn (Ex
      Zn), carbonate bound Zn (Carb-Zn), manganese oxide bound Zn (OxMn-Zn), tightly
      organic bound Zn (Sbo-Zn), and mineral Zn (Min-Zn) contents had no significant
      differences among the treatments, but the soil weakly organic bound Zn (Wbo-Zn)
      content was significantly higher under Zn fertilization, compared with the
      treatments control and straw addition alone. It was considered that the Zn in
      maize straw could be easily transformed into soil DTPA-Zn, though the Zn
      concentration in straw was rather low. Therefore, Zn fertilization combined with
      returning maize straw into filed could be an effective way to improve the Zn
      supply capacity of calcareous soil.

PMID- 22384591
TI  - [Effects of different planting modes on soil nitrogen transformation and related
      enzyme activities].
AB  - A 2-year field experiment was conducted to study the dynamics of soil nitrogen
      content and urease, proteinase, and nitrate reductase activities in a
      wheat/maize/soybean relay strip intercropping system under effects of five
      planting modes, i.e., wheat-soybean (A1), wheat-sweet potato (A2), maize (A3),
      wheat/maize/soybean (A4), and wheat/maize/sweet potato (A5). Among the five
      planting modes, A4 increased the soil total nitrogen content and urease and
      protease activities at flowering (or spinning) and maturing stages, and the total
      nitrogen content and urease and protease activities were relay strip
      intercropping > single cropping, soybean > sweet potato, and fringe row > central
      row. A4 decreased the NO3(-)-N and NH4(+)-N contents of wheat and maize soil, and
      the nitrate reductase activity of wheat soil. The nitrate reductase activity of
      maize soil was higher in single cropping than in relay strip intercropping at
      jointing stage but was in adverse at maize spinning and maturiting stages, and
      the nitrate reductase activity of soybean soil was higher than that of sweet
      potato soil. At the branching stage of soybean, the soil NO3(-)-N and NH4(+)-N
      contents and nitrate reductase activity were higher in single cropping than in
      relay strip intercropping; whereas at flowering and maturing stages, the soil
      NO3(-)-N and NH4(+)-N contents and nitrate reductase activity were in the
      sequences of strip intercropping > single cropping, soybean > sweet potato, and
      center row > fringe row.

PMID- 22384592
TI  - [Translocation and transformation characteristics of fertilizer nitrogen in paddy
      soil: a study with simulated soil column].
AB  - Aimed to understand the translocation and transformation characteristics of
      applied fertilizer nitrogen in paddy soil, a simulated soil column experiment was
      conducted in laboratory to study the variations of soil mineral nitrogen along
      the profile under the application of 360 mg x kg(-1) (3 folds of conventional
      application rate) of urea- and ammonium sulfate nitrogen. In the experimental
      period, the soil NH4(+)-N and NO3(-)-N contents in the control (no fertilization)
      had less change, and no significant differences among different soil layers.
      Applying urea- and ammonium sulfate nitrogen resulted in a significant increase
      of soil NH4(+)-N and NO3(-)-N in 0-50 mm layer, being 186.0-2882.1 mg x kg(-1)
      and 268.7-351.5 mg x kg(-1), and 4.8-242 times and 5.7-316 times of those in CK,
      respectively. However, the NH4(+)-N and NO3(-)-N contents below 50 mm soil depth
      were similar to those in CK, indicating that the translocation and transformation
      of applied fertilizer nitrogen mainly occurred in 0-50 mm soil layer. The
      translocation of fertilizer nitrogen mostly occurred in the first 14 days after
      fertilization. In the whole experimental period, the NH4(+)-N and NO3(-)-N
      contents in each soil layer under the application of ammonium sulfate were 0.7
      2.0 times of those under the application of urea, and the nitrification rate was
      0.9-1.4 times of that, suggesting the higher transformation rate of applied
      ammonium sulfate in paddy soil, as compared with applied urea.

PMID- 22384593
TI  - [Effects of nitrogen fertilization rate and planting density on cotton biomass
      and nitrogen accumulation in extremely early mature cotton region of Northeast
      China].
AB  - Taking two cotton cultivars Liaomian 19 and NuCOTN 33B with different growth
      periods as test materials, a field experiment was conducted to study the effects
      of different nitrogen fertilization rates (0, 240 and 480 kg N x hm(-2)) and
      different planting densities (75000, 97500 and 120000 plants x hm(-2)) on the
      cotton biomass, nitrogen accumulation, and accumulative nitrogen utilization in
      the planting region of extremely early mature cotton in Northeast China. The
      dynamics of cotton biomass and nitrogen accumulation of the two cultivars with
      their growth process followed Logistic model. Both nitrogen fertilization rate
      and planting density had significant effects on the cotton nitrogen accumulation
      dynamics and the cotton yield and quality. In all treatments, the beginning time
      of rapid accumulation of nitrogen was about 13 d earlier than that of biomass. In
      treatment plant density 97500 plants x hm(-2) and nitrogen fertilization rate 240
      kg x hm(-2), the eigenvalues of the dynamic accumulation models of nitrogen and
      biomass for the two cultivars were most harmonious, lint yield was the highest,
      fiber quality was the best, and accumulative nitrogen utilization efficiency was
      the highest. In the study region, the earlier beginning time of rapid
      accumulation of nitrogen and biomass and their higher accumulation rates were
      benefit to the formation of higher cotton yield.

PMID- 22384594
TI  - [Effects of exogenous spermidine on lipid peroxidation and membrane proton pump
      activity of cucumber seedling leaves under high temperature stress].
AB  - Taking a relatively heat-resistant cucumber (Cucumis sativus) cultivar 'Jinchun
      No. 4' as test material, a sand culture experiment was conducted in growth
      chamber to investigate the effects of foliar spraying spermidine (Spd) on the
      lipid peroxidation, membrane proton pump activity, and corresponding gene
      expression of cucumber seedling leaves under high temperature stress. Compared
      with the control, foliar spraying Spd increased the plant height, stem diameter,
      dry and fresh mass, and leaf area significantly, and inhibited the increase of
      leaf relative conductivity, malondialdehyde (MDA) content, and lipoxygenase (LOX)
      activity effectively. Foliar spraying Spd also helped to the increase of leaf
      plasma membrane- and tonoplast H(+)-ATPase activity, but no significant
      difference was observed in the gene expression levels. These results suggested
      that exogenous Spd could significantly decrease the leaf lipid peroxidation and
      increase the proton pump activity, and thus, stabilize the leaf membrane
      structure and function, alleviate the damage induced by high temperature stress,
      and enhance the heat tolerance of cucumber seedlings.

PMID- 22384595
TI  - [Carbon source utilization characteristics of microbial communities in a
      petroleum-contaminated soil in Daqing Oil Field, Northeast China].
AB  - By using Biolog technique, this paper studied the carbon source utilization
      characteristics of microbial communities in different layers (0-10 cm, 10-20 cm,
      and 20-30 cm) of a petroleum-contaminated soil near an oil well having exploited
      for 36 years in Daqing Oil Field. Petroleum contamination enhanced the metabolic
      activity of the soil microbial communities obviously. In the three layers of the
      petroleum-contaminated soil, the metabolic activity of the microbes was higher
      than that of the control, and there existed significant differences between
      different layers of the petroleum-contaminated soil. The carbon source metabolic
      capacity of the microbes in different layers of the petroleum-contaminated soil
      was in the order of 20-30 cm > 10-20 cm > 0-10 cm. Petroleum contamination made
      the kinds of soil carbon source and the metabolic diversity of soil microbes
      increased, being more obvious in 10-20 cm and 20-30 cm soil layers but less
      change in 0-10 cm soil layer. In the contaminated soil, the majority of the
      carbon sources utilized by the microbes in 10-20 cm soil layer were carbohydrates
      instead of the carboxylic acids in non-contaminated soil, whereas the majority of
      the carbon substrates utilized in 20-30 cm soil layer were carboxylic acids. All
      the results suggested that petroleum-contaminated soil had its unique microbial
      community structure and peculiar microbial carbon source utilization
      characteristics.

PMID- 22384596
TI  - [Effects of plant hedgerow on population dynamics of wheat aphid and its natural
      enemies].
AB  - This paper studied the effects of planting different kinds of plant hedgerow
      (Amorpha fruticosa, Vetiveria zizanioides, Eulaliopsis binata, and Medicago
      sativa) on the population dynamics of wheat aphid and its natural enemies in the
      hillside wheat fields in Ziyang City of Sichuan Province, Southwest China. On the
      20 degrees hillside, A. fruticosa hedgerow inhibited the occurrence of wheat
      aphid in the wheat field significantly, and the parasitoid densities were equal
      to or significantly lower than those in the wheat field with V. zizanioides
      hedgerow. On the 12 degrees hillside, M. sativa and E. binata hedgerows delayed
      the peak time of wheat aphid occurrence, and E. binata hedgerow suppressed the
      wheat aphid population density significantly. In the wheat field with M. sativa
      hedgerow, the parasitoid densities were significantly higher than those with no
      hedgerow. An equal or significantly higher ladybird density was observed in the
      field with M. sativa hedgerow. The olfactory responses showed that E. binata
      volatiles had repellent effect on both Sitobion avenae and Rhopalosiphum padi,
      but attracted a spider species of oxyopidae. M. sativa volatiles attracted S.
      avenae, whereas neither M. sativa nor E. binata volatiles caused obvious behavior
      response of ladybird adults. Therefore, planting A. fruticosa and E. binata as
      the hedgerows in hillside wheat fields could not only prevent the soil erosion
      from seasonal rainfall, but also benefit the control of pest insects.

PMID- 22384597
TI  - [Ecosystem health assessment of economic zone on the west side of Taiwan Strait,
      China].
AB  - Based on the standards of regional ecosystem health, including vigor,
      organizational structure, resilience, ecological function, and public health, and
      in considering of anthropogenic pressure and response countermeasures, an index
      system for the ecosystem health assessment of the economic zone on the west side
      of the Taiwan Strait (Haixi Zone) was built, and, aiming at the characteristics
      of nature and humanity of regional ecosystem health, the weights of the indices
      were given by analytic hierarchy process and mean square difference method. Fuzzy
      comprehensive assessment was utilized to establish the ecosystem health
      assessment model of Haixi Zone. The assessment showed that in 2008, the ecosystem
      health state of Haixi Zone was superior, and the anthropogenic pressure was
      relatively gentle. Overall, the regional ecosystem health status was good, but
      had spatial difference. Owing to the restriction of response countermeasures such
      as fixed assets investment and education expenditure. The regional ecosystem
      health status of Longyan, Quanzhou, Wenzhou, Chaozhou and Jieyang was worse than
      the health state of these cities in 2008. The overall ecosystem health status of
      the Zone in 2000 and 2008 was better than that in 1992, and the main driving
      factors were mainly economic vigor, organizational structure, human health,
      population pressure, and investment. However, the overall ecosystem health status
      of Haixi Zone in 2008 was worse than that in 2000, due to the expansion of built
      up land, the decrease in natural landscape, and the enhancement of human
      disturbances.

PMID- 22384598
TI  - [Spatial patterns of eco-environmental vulnerability in Daqing City].
AB  - This paper established an index system for the assessment of eco-environmental
      vulnerability in Daqing City, from the aspects of sensitivity and response
      capability, and aiming at the major disturbances from crude oil exploitation and
      production activities. The improved entropy method was adopted to evaluate the
      weights of the indices, and the spatial patterns of eco-environment vulnerability
      in the City were analyzed, according to the model functions. In 2009, the more
      sensitive areas of the eco-environment in the City were mainly concentrated in
      the intensive regions of crude oil exploitation, processing, and petrochemical
      industry, and the ecological problems such as land salinization were the
      secondary causes for this higher sensitivity. The overall response capability of
      the eco-environment to unfavorable disturbances was relatively high, which
      reduced the eco-environment vulnerability to some extent. There was a great
      spatial difference in the eco-environment vulnerability in the City. The
      vulnerability was comparatively higher in the districts of Honggang, Sartu and
      Longfeng, with the degree being 0.80, 0.71 and 0.68, but lower in Ranghulu and
      Datong, with the degree of 0.20 and 0.04, respectively.

PMID- 22384599
TI  - [Distribution and composition of organochlorine pesticides in farmland top soils
      of Anhui Province].
AB  - By using ultrasonic method and GC/ECD, this paper analyzed the distribution and
      composition of 8 kinds of organochlorine pesticides (alpha-HCH, beta-HCH, gamma
      HCH, delta-HCH, op'-DDE, pp'-DDD, alpha-endosulfan, and chlorothalonil) in
      farmland top soils (0-20 cm) in 19 districts of Anhui Province, East China. The
      total concentration of the pesticides in the top soils ranged from 0 to 23.75
      microg x kg(-1), among which, pp'-DDD and gamma-HCH were the major pollutants,
      with the mean concentration being 13.83 and 13.49 microg x kg(-1), respectively.
      As compared with the analyses in 1990, the present mean concentration of HCH had
      an obvious decreasing trend, but was still higher than that in the top soils in
      other regions of China and in other countries. The mean concentrations of OCPs,
      HCHs and pp'-DDD in the test top soils were 48.58, 28.64 and 13.83 microg x kg(
      1), respectively, not surpassed the first grade level (< 50 microg x kg(-1)) of
      the China National Soil Environmental Quality Standards (GB 15618-1995),
      suggesting that the farmland top soils in these districts of Anhui Province were
      less polluted.

PMID- 22384600
TI  - [Biosorption of crystal violet and malachite green by Rhodotorula graminis Y-5].
AB  - With a shaker, this paper studied the characteristics of the biosorption of
      crystal violet and malachite green by Rhodotorula graminis Y-5 under different
      adsorption time, initial pH, and temperature, as well as the desorption and
      recycling use of the dyes. The biosorption of crystal violet and malachite green
      by R. graminis Y-5 had the peaks (93.8% and 87.7%, respectively) at pH 7.0, dye
      concentration 50 mg x L(-1), 150 r x min(-1), 30 degrees C, and lasting 10 hours.
      After desorption, the biosorption rate of crystal violet and malachite green by
      R. graminis was 85.5% and 78.5%, respectively, indicating that the biosorption of
      crystal violet and malachite green was reversible, and the recycling use of the
      dyes by R. graminis was quite good, i. e., the dyes were renewable and could be
      recycled. Biosorption could be the mechanism of the decolorization of the dyes.
      The dyes were mostly adsorbed on the R. graminis surface -OH. The adsorption
      process was fast, efficient, and reversible, suggesting that R. graminis had a
      high potential for waste water treatment.

PMID- 22384601
TI  - [Induce of laccase from Trametes gallica and its degradation on neutral dyes and
      organophosphorus pesticides].
AB  - The characteristics of the induction of laccase in Trametes gallica under
      different initial cultural pH, incubation time by different inducers were
      discussed, as well as the effects of temperature, pH and time on laccase
      degradation of six dyes and four organophosphors. The results showed that RB
      bright blue, ABTS and o-toluidine affected the production of laccase at different
      levels, and ABTS was the best inductive agent in our test conditions, whose
      optimal initial pH and incubation time were 4.0 and 13 days, respectively. The
      appropriate reaction temperature of the laccase produced was 38 degrees C, and it
      got a good stability, for it could retain 78.6% of the enzyme activity after 20
      min holding at 40 degrees C. Mediated by ABTS, the optimal temperature for
      laccase to degrade the six types of neutral dyes could be divided into two cases,
      that was 30 degrees C (neutral black, neutral bordeaux, neutral pink, methyl
      orange) and 60 degrees C (neutral dark yellow, cresol red), the optimal pH were
      6.0 (neutral black), 2.0 (neutral bordeaux, neutral pink) and 4.0 (methyl orange,
      neutral dark yellow, cresol red), respectively, while the optimal times
      separately were 6 h (methyl orange, neutral dark yellow, cresol red), 12 h
      (neutral pink) and 24 h (neutral bordeaux). And using the same inductive agent,
      the best temperature for laccase to degrade dimethoate, chlorpyrifos, trichlorfon
      and parathion-pyridazine was 25 degrees C, the suitable time was 9 h, and the
      optimal pH was 10.0 for dimethoate, chlorpyrifos and parathion-pyridazine, and
      8.0 for trichlorfon.

PMID- 22384602
TI  - [Location selection for Shenyang urban parks based on GIS and multi-objective
      location allocation model].
AB  - Based on geographic information system (GIS) technology and multi-objective
      location-allocation (LA) model, and in considering of four relatively independent
      objective factors (population density level, air pollution level, urban heat
      island effect level, and urban land use pattern), an optimized location selection
      for the urban parks within the Third Ring of Shenyang was conducted, and the
      selection results were compared with the spatial distribution of existing parks,
      aimed to evaluate the rationality of the spatial distribution of urban green
      spaces. In the location selection of urban green spaces in the study area, the
      factor air pollution was most important, and, compared with single objective
      factor, the weighted analysis results of multi-objective factors could provide
      optimized spatial location selection of new urban green spaces. The combination
      of GIS technology with LA model would be a new approach for the spatial
      optimizing of urban green spaces.

PMID- 22384603
TI  - [Drought-resistance evaluation of marigold cultivars based on multiple statistics
      analysis].
AB  - By the methods of principal component analysis, subordinate function, and cluster
      analysis, a comprehensive evaluation was conducted on the drought-resistance of
      16 physiological indices of nine marigold cultivars. Under drought stress, the 16
      physiological indices had different responses, among which, free proline (Pro),
      H2O2, and ascorbate peroxidase (APX) showed the greatest sensitivity. There
      existed significant correlations in the drought-resistance coefficients of parts
      of the physiological indices. Four principal factors presented 88.6% of the
      information of the 16 indices, and the cultivars 'Janie' and 'Gate gold',
      'Bonanzn', 'Janie', and 'Chokdee' had the strongest drought-resistance for the 4
      principal factors, respectively. The comprehensive evaluation value of the
      drought-resistance of the 9 cultivars was in the order of 'Janie' > 'Gate gold' >
      'Bonanza' > 'Chokdee' > 'Giant' > 'Great hero' > 'Little hero' > 'Durango' >
      'Discovery'. The 9 cultivars could be clustered into 3 groups, and 'Gate gold',
      'Janie', 'Bonanza' and 'Chokdee' belonged to the drought-resistance group.

PMID- 22384604
TI  - [Effects of macro-jellyfish abundance dynamics on fishery resource structure in
      the Yangtze River estuary and its adjacent waters].
AB  - Based on the bottom trawl survey data in May 2007 and May and June 2008, this
      paper analyzed the effects of the abundance dynamics of macro-jellyfish on the
      species composition, distribution, and abundance of fishery resource in the
      Yangtze River estuary and its adjacent waters. From May 2007 to June 2008, the
      average catch per haul and the top catch per haul of macro-jellyfish increased,
      up to 222.2 kg x h(-1) and 1800 kg x h(-1) in June 2008, respectively. The macro
      jellyfish were mainly distributed in the areas around 50 m isobath, and not
      beyond 100 m isobath where was the joint front of the coastal waters of East
      China Sea, Yangtze River runoff, and Taiwan Warm Current. The main distribution
      area of macro-jellyfish in June migrated northward, as compared with that in May,
      and the highest catches of macro-jellyfish in May 2007 and May 2008 were found in
      the same sampling station (122.5 degrees E, 28.5 degrees N). In the sampling
      stations with higher abundance of macro-jellyfish, the fishery abundance was low,
      and the fishery species also changed greatly, mainly composed by small-sized
      species (Trachurus japonicus, Harpadon nehereus, and Acropoma japonicum) and
      pelagic species (Psenopsis anomala, Octopus variabilis) and Trichiurus japonicus,
      and P. anomala accounted for 23.7% of the total catch in June 2008. Larimichthys
      polyactis also occupied higher proportion of the total catch in sampling stations
      with higher macro-jellyfish abundance, but the demersal species Lophius litulon
      was not found, and a few crustaceans were collected. This study showed that macro
      jellyfish had definite negative effects on the fishery community structure and
      abundance in the Yangtze River estuary fishery ecosystem, and further, changed
      the energy flow patterns of the ecosystem through cascading trophic interactions.
      Therefore, macro-jellyfish was strongly suggested to be an independent ecological
      group when the corresponding fishery management measures were considered.

PMID- 22384605
TI  - [Macrobenthos community structure and its relations with environmental factors in
      Taihu River basin].
AB  - An investigation was conducted on the macrobenthos at 37 sampling sites in the
      Taihu River basin in August 2009 and May 2010. A total of 69 macrobenthos species
      were collected, of which, 15 species (21.7% of the total) were oligochaetas, 16
      species (23.2%) were mollusks, 5 species (7.2%) were crustaceans, 27 species
      (39.1%) were aquatic insects, and 6 species (8.7%) were polychaetes. Based on the
      species composition and relative abundance, and by using two-way indicators
      species analysis (TWINSPAN) and detrended correspondence analysis (DCA), the 37
      sampling sites were divided into four groups. In the first group, polychaetes and
      mollusks such as Nephthys sp. and Corbicula fluminea were the indicator species;
      in the second group, polychaetes and mollusks such as Grandidierella aihuensis
      and Semisulcospira libertina were the indicator species; in the third and fourth
      groups, the indicator species were the annelids such as Limnodrilus hoffmeisteri
      and the Tubifex tubifex and chironomidae larvae, respectively. The canonical
      correspondence analysis (CCA) indicated that water conductivity and total
      nitrogen were the main environmental factors affecting the distribution of
      macrobenthos, and the factors water depth, diaphaneity, COD(Cr), ammonium
      nitrogen, nitrate nitrogen, and chlorophyll a also had definite effects.

PMID- 22384606
TI  - [Effects of water temperature and edible algal density on the population dynamics
      and sexual reproduction of Moina irrasa].
AB  - This paper studied the population dynamics and sexual reproduction of Moina
      irrasa at different water temperature and edible algal density. The population
      density of M. irrasa was obviously higher at high than at medium and low
      densities of edible algae, with the maximum at high edible algal density and 20
      degrees C. At the same temperatures, the average number of the offsprings first
      produced by per female M. irrasa declined with decreasing edible algal density,
      and the maximum value appeared at 25 degrees C and at high edible algal density.
      The male offsprings produced were obviously higher at high than at medium and low
      edible algal densities. There was a significant correlation between the male
      density and the population density of M. irrasa. The number of ephippia produced
      by M. irrasa declined with decreasing edible algal density, and was higher at 25
      degrees C than at other temperatures. Edible algal density had larger effects on
      the population dynamics and sexual reproduction of M. irrasa, as compared with
      temperature.

PMID- 22384607
TI  - [Potential errors in measuring tree transpiration based on thermal dissipation
      method].
AB  - Transpiration is a major component of vegetation evapotranspiration, and a core
      in the study of plant water physiological ecology. Its measurement methods
      attracted extensive attention, among which, thermal dissipation is considered as
      an optimal method for measuring tree transpiration. Numerous studies showed that
      thermal dissipation method was relatively accurate in measuring individual tree
      transpiration and stand-scale water consumption. However, there exist potential
      errors between the true value and the measurements during measurement process. In
      this paper, the potential errors of thermal dissipation method in measuring sap
      flux density and of the temperature difference determination from single tree to
      stand-scale were reviewed, and the research prospects on the potential errors of
      thermal dissipation method in China were discussed. The corresponding solutions
      were also proposed.

PMID- 22384608
TI  - [Sexual difference of insect phototactic behavior and related affecting factors].
AB  - Flight-to-light is one of the major behaviors of nocturnal insects. Previous
      studies have demonstrated that many nocturnal insect species have noticeable
      sexual difference in the behavior of flight-to-light, and many factors may
      contribute to this kind of difference. This paper reviewed the sexual difference
      of insect phototactic behavior in terms of the difference in flying distance and
      height between female and male adults due to their different flying capability,
      the distinct difference in the response to light resource due to the different
      structure of compound eyes between female and male adults, and the difference in
      the sensitivity to the light source and other environmental factors between
      female and male adults. The applied aspects and future research directions of the
      sexual difference of nocturnal insect phototactic behavior were also discussed.

PMID- 22384609
TI  - [Ecosystem services evaluation based on geographic information system and remote
      sensing technology: a review].
AB  - Ecosystem services evaluation is a hot topic in current ecosystem management, and
      has a close link with human beings welfare. This paper summarized the research
      progress on the evaluation of ecosystem services based on geographic information
      system (GIS) and remote sensing (RS) technology, which could be reduced to the
      following three characters, i. e., ecological economics theory is widely applied
      as a key method in quantifying ecosystem services, GIS and RS technology play a
      key role in multi-source data acquisition, spatiotemporal analysis, and
      integrated platform, and ecosystem mechanism model becomes a powerful tool for
      understanding the relationships between natural phenomena and human activities.
      Aiming at the present research status and its inadequacies, this paper put
      forward an "Assembly Line" framework, which was a distributed one with scalable
      characteristics, and discussed the future development trend of the integration
      research on ecosystem services evaluation based on GIS and RS technologies.

PMID- 22384610
TI  - [Effects of drought stress on the biomass distribution and photosynthetic
      characteristics of cluster mulberry].
AB  - One-year-old Morus alba seedlings were cultivated in pots containing soil with
      different water contents to study the biomass, chlorophyll fluorescence
      parameters, net photosynthesis rate, stomatal conductance, transpiration rate and
      water use efficiency of the seedlings in response to diverse water stress. The
      results showed that the aboveground biomass and total biomass decreased with
      increasing water stress. However, more photosynthetic products were transferred
      to the roots in relation to the aboveground parts to make the root-shoot ratio
      increase. The fluorescence parameters, such as F(o), F(v) and F(v)/F(m), and
      stomatal conductance, transpiration rate and water use efficiency decreased with
      increasing water stress.

PMID- 22384611
TI  - [Effects of wheat planted adjacent to rape on the major pests and their natural
      enemies in wheat field].
AB  - Based on the dynamic analysis of insect community structure characteristics, an
      investigation was conducted on the composition, abundance, and stability of wheat
      aphids and their major natural enemies in the wheat field adjacent to rape field
      in Handan City, Hebei Province in 2008-2009. The wheat and rape fields had the
      similar composition of insect communities. The main pests were aphids, their
      predatory natural enemies included ladybirds, green lacewings, spiders, and hover
      flies, and their parasitic natural enemies were wasps. In 2008-2009, the
      composition of insect communities in the wheat and rape fields had definite
      changes, but the common features were the lowest abundance of aphids and the
      highest abundance of predatory and parasitic natural enemies in wheat field
      adjacent to rape field. The insect community, aphid sub-community, and predatory
      natural enemy' s sub-community had a high stability in the wheat field adjacent
      to rape field and a low stability far from the rape field, suggesting that
      planting wheat adjacent to rape could effectively protect and make use of the
      natural enemies and promote their control ability on wheat aphids in wheat field.

PMID- 22384612
TI  - "Internal coasting" for prevention of ovarian hyperstimulation syndrome (OHSS) in
      IVF/ICSI.
AB  - OBJECTIVES: To prevent OHSS by interruption of the early stage of stimulation
      ("internal coasting"). DESIGN: Prospective, randomized study MATERIAL AND
      METHODS: 139 women who had unsuccessfully undergone standard long protocol ICSI
      procedure, complicated by OHSS of moderate or severe degree. The women were
      randomized to two groups--68 undergoing stimulation in which, after 2 days of 225
      IU hMG there were 2 days without hMG, and then, for the remainder of the
      stimulation period, 150 IU hMG. The control group (71 women) received standard
      doses of hMG, as in the first ICSI cycle. The main outcome measures was the
      prevalence and severity of OHSS, implantation and pregnancy rates. RESULTS: There
      were 39 cases of OHSS of moderate (32) and severe (7) degree in the control group
      and 7 (moderate) cases in the investigated group (p = 0.05). No differences were
      found in the implantation rate and pregnancy rate, the mean number of oocytes
      fertilized, fertilization rate and the mean number of embryos transferred.
      CONCLUSION: Stimulation with internal coasting is safe for women at a high risk
      of OHSS. It does not negatively influence fertilization, implantation or
      pregnancy rates.

PMID- 22384613
TI  - Prevalence of diastasis recti abdominis in the population of young multiparous
      adults in Turkey.
AB  - OBJECTIVES: To determine the prevalence and factors associated with diastasis
      recti abdominis (DRA) MATERIAL AND METHODS: Between January 2011 and May 2011, we
      examined 95 patients, aged between 19-24, for the presence of DRA during an
      ultrasonographic exploration in Mus Obstetrics and Gynecology Hospital, Mus,
      Turkey DRA was graded by the number of fingerbreadths between the medial edges of
      the bellies of the rectus abdominis muscle, 3-4 cm above the umbilicus. The
      exclusion criteria included urogynecologic problems since childhood, excessive
      protrusion of the vagina due to loss of support, pregnancy obesity less than 6
      months postpartum. The relationship between DRA and parity previous abdominal
      surgery pelvic relaxation as well as type of parity was assessed. RESULTS:
      Positive correlation was found between parity and DRA (r = 0.77; p < 0.001).
      Although there was no significant difference between DRA and the type of delivery
      among primiparous patients (p = 0.556), DRA increased significantly in the second
      cesarean section patients (p = 0.004). In this trial, cystocele and rectocele
      were established in 57% and 43% of patients with DRA, while descensus uteri was
      present in 10 (52%) patients. CONCLUSIONS: Increased parity and recurrent
      abdominal surgery seem to increase the risk of DRA. However; the importance of
      DRA in the young women remains unknown.

PMID- 22384614
TI  - [Changes in calprotectin concentration--inflammation marker in serum of women
      with gynecological cancer].
AB  - OBJECTIVES: Malignant tumors of the ovary and uterus remain to be a diagnostic
      and therapeutic problem in Poland, mainly due to the lack of effective diagnosis
      of their early stages. There is a relation between an impaired immune system,
      especially the process of inflammation and the pathogenesis of these tumors. The
      aim of the study was to assess the concentration of calprotectin--a inflammation
      marker in the serum of women with ovarian or uterine cancer. MATERIAL AND
      METHODS: The study group included 96 women, aged 21 to 72 (mean age: 46.7 +/-
      13.6 years) with the diagnosed and histologically confirmed ovarian or uterine
      tumor The control group consisted of 30 women aged 24-60 (mean age 45.6 +/- 8.9
      years), showing no pathological disorders or any inflammations of the
      reproductive system. The concentration of calprotectin was evaluated with the use
      of the immunoenzymatic method ELISA using the Calprotectin ELISA (serum) kit by
      DRG Instruments (Germany). RESULTS: In serum of women with tumors the
      calprotectin level was significantly higher comparing to the control group (p <
      0.0001). The highest calprotectin levels in women with ovarian cancer (mean +/-
      SD: 231.84 +/- 13.74 ng/ ml) and uterine cancer (mean +/- SD: 166.23 +/- 13.36
      ng/ml) were observed and were significantly higher comparing to women with
      ovarian serous adenomas (mean +/- SD: 72.60 +/- 9.75 ng/ml) and fibroids of the
      uterus (mean +/- SD: 72.31 +/- 9.19 ng/ml) (p < 0.0001). CONCLUSIONS: In women
      with ovarian and uterine cancer a significant increase in the concentration of
      calprotectin was observed, suggesting an inflammatory process that accompanies
      cancer. These changes are especially pronounced in women with cancer which
      probably indicates autocrine production of the protein by cancer cells.
      Estimation of the parameter examined in the serum may improve differential
      diagnosis of malignant and benign ovarian and uterine cancers, however it
      requires further investigation.

PMID- 22384615
TI  - [Maternal body mass index and gestational weight gain and their association with
      perinatal outcome in women with gestational diabetes].
AB  - OBJECTIVES: Maternal overweight and obesity constitute the most important factors
      causing perinatal complications. The purpose of the study was to analyze
      obstetrical results in overweight/obese pregnant women with gestational diabetes
      in relation to Institute of Health recommendations concerning gestational weight
      gain and assessment of the role of prepregnancy BMI in prediction of macrosomia,
      pregnancy induced hypertension and cesarean deliveries. MATERIAL AND METHODS:
      Retrospective analysis of 209 overweight and obese pregnant women with
      gestational diabetes divided into 4 subgroups according to The National Institute
      of Health (USA) recommendations. The following data were included in the
      analysis: gestational week in which GDM was diagnosed; HbA1c level in the first
      and third trimester just before delivery; incidence of pregnancy induced
      hypertension; incidence of cesarean deliveries; incidence of macrosomia. The
      following data of II, III, IV subgroups were compared to these found in I
      subgroup which was classified as the control group. Selected obstetric parameters
      were also compared between subgroups II, III, IV RESULTS: The selected parameters
      of subgroups II, III, IV were not significantly different from these of subgroup
      I. Pregnancy induced hypertension was diagnosed more frequently among subgroup II
      in comparison to subgroup III. Using ROC curves analysis, the role of pre
      pregnancy BMI was found in the prognosis of: birth weight greater than 4300 g,
      pregnancy induced hypertension, cesarean delivery CONCLUSIONS: 1. The application
      of the National Institute of Health recommendations on gestational weight gain is
      limited in case of overweight or obese pregnant women with gestational diabetes
      mellitus. 2. Excessive weight gain during pregnancy according to National Health
      Institute recommendations may increase the risk of developing pregnancy induced
      hypertension in comparison to a pregnant women with weight gain less than
      recommended, but greater than zero. 3. Increased prepregnancy BMI has a role in
      prediction of birth weight greater than 4300 g, pregnancy induced hypertension,
      cesarean delivery

PMID- 22384616
TI  - [Maternal hyperoxygenation test in prediction of fetal lung hypoplasia-
      preliminary report].
AB  - OBJECTIVES: The aim of our study was to present the detailed execution and
      interpretation of the hyperoxygenation test in the fetus. MATERIAL AND METHODS:
      This was a retrospective investigation of fetuses examined in The Department for
      Diagnosis and Prophylaxis of Congenital Malformations (Polish Mothers Memorial
      Hospital Institute and Medical University in Lodz) between January 2006 and
      December 2009, in whom in addition to the routine echocardiographic examination
      the hyperoxygenation test was performed. Indications for such an extended
      evaluation were suspected fetal malformations and pulmonary hypoplasia. Changes
      in the fetal pulmonary circulation before and after maternal exposure to
      hyperoxygenated air together with the newborn follow-up were analyzed. RESULTS:
      Clinical outcome was available for 42 of 52 cases: 16 patients died (including 11
      cases with negative hyperoxygenation test), whereas 24 patients were discharged
      home (including 17 cases with positive hyperoxygenation test). The probability of
      survival for fetuses with the positive test was significantly higher than for
      fetuses with the negative one (p = 0.016, Fischer's exact test). CONCLUSIONS:
      Based on changes evoked in the fetal pulmonary circulation, the hyperoxygenation
      test seems helpful in predicting impaired fetal lung development Functional
      assessment of the fetal pulmonary circulation may be useful in predicting fetal
      lung hypoplasia and respiratory failure in the neonate.

PMID- 22384617
TI  - Dietary antioxidant levels in hyperemesis gravidarum: a case control study.
AB  - OBJECTIVES: Dietary antioxidant intake decreases the risk of many diseases.
      Hyperemesis gravidarum (HG) is the most common eating disorder during pregnancy
      Therefore, the authors conducted this prospective and case control study to
      evaluate dietary antioxidant levels of women with HG and compare with healthy
      pregnant women. MATERIAL AND METHODS: This prospective case control study was
      conducted at a government hospital in the southeastern region of Turkey from
      February 2010 to May 2010. A total of 100 pregnant women were included into the
      study Dietary antioxidant levels (DAL) were measured according to the new 92-item
      antioxidant nutrient questionnaire developed by Satia et al. 50 women with HG and
      50 healthy pregnant women were evaluated. Statistical analyses were carried out
      with statistical packages for SPSS 15.0 for Windows (SPSS Inc., Chicago, IL,
      USA). RESULTS: There were no statistically significant differences between the
      groups regarding the age of the patients, gestational age, educational status,
      body height and weight (p > .05). Vitamin E, E equivalent, vitamin C, carotene
      and vitamin A levels were significantly lower in women with HG (p < .05). The
      results of logistic regression method for these variables including odds ratio
      (95 % CI) were as follows: 10.07 (1.52-66.51), 7.37 (2.66-20.41), 4.26 (2.66
      20.41), 3.66 (2.38-5.63) and 2.75 (1.56-4.85), respectively CONCLUSION: According
      to this study, vitamin E, E equivalent, vitamin C, carotene and vitamin A levels
      of women may play a role in the pathogenesis of HG. Therefore, diet
      recommendations should be given by clinicians before pregnancy

PMID- 22384618
TI  - Prediction of mild and severe preeclampsia with blood pressure measurements in
      first and second trimester of pregnancy.
AB  - OBJECTIVES: The study was designed to determine the accuracy of using systolic
      (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), and
      increase of blood pressure (BP) to predict Preeclampsia (PE). MATERIALS AND
      METHODS: We examined 300 normotensive and 100 PE pregnancies divided in two
      subgroups: mild (n = 67) and severe (n = 33) PE. The patients had a BP check in
      first and second trimester (SBFP DBP and MAP). RESULTS: We found out significant
      difference between the groups, but what is more important is that the difference
      in BP values (especially diastolic and MAP) existed before the pathological
      increase of the BP above the normal values. This was happening most often after
      31 wg (at 92.5%) and less often after 26 wg (at 7.5%) at the pregnancies with
      mild PE while at the pregnancies with severe PE, 18,2% had increased tension
      after 21 wg; 24% in the period of 26-30 wg and 57.58% after 31 wg. CONCLUSION:
      Based on the results we could conclude that when BP is measured in the first or
      second trimester of pregnancy the MAP is a better predictor for PE than SBP and
      DBPR.

PMID- 22384619
TI  - [Sacral nerve stimulation in the treatment of the lower urinary tract function
      disorders].
AB  - Functional disorders of the female lower urinary tract like urge incontinence,
      idiopathic urinary retention and symptoms of urgency-frequency occasionally do
      not respond properly to classical behavioral and pharmacological therapy
      Therefore, additional alternative therapies are needed to alleviate these
      bothersome symptoms. Sacral neuromodulation (SNS) utilize mild electrical pulses
      which activate or suppress neural reflexes responsible for voiding by stimulating
      the sacral nerves that innervate the bladder, external urethral sphincter and
      pelvic floor muscles. The exact mechanism of SNS action is not yet fully
      understood but it is assumed that it influences the neuroaxis at different levels
      of the central nervous system and restores the balance between inhibitory and
      activatory control over the voiding reflex. There is numerous evidence on the
      success of SNS not only in the treatment of refractory urge incontinence in adult
      and children but also in idiopathic urinary retention and symptoms of urgency
      frequency

PMID- 22384620
TI  - Polypectomy followed by adjuvant chemotherapy in a patient with sarcoma
      botryoides of the uterine cervix--case report and review of the literature.
AB  - BACKGROUND: Embryonal rhabdomyosarcoma in a form of a polyp of the uterine cervix
      occurs mainly in young women in their second decade of life. The characteristic
      microscopic features are: the submucosal cambium layer and the presence of
      rhabdomyoblasts in the stroma. So far the treatment has not been well defined and
      ranges from conservative to radical surgery CASE: The presented case is a 22-year
      old woman with cervical polyp. Polypectomy with D&C was performed in 2005 and the
      microscopic examination revealed rhabdomyosarcoma botryoides. Detailed
      examination diagnosed stage 1a of the disease. The patient received 6 cycles of
      chemotherapy (Vincristine and Actinomycin). CONCLUSION: Conservative treatment
      may be considered in young women with favorable prognostic factors who wish to
      preserve their fertility Polypectomy followed by chemotherapy is a possible
      option for such patients.

PMID- 22384621
TI  - [Low bone mass in a 17-year-old girl in the course of yolk sac tumor treatment-
      case report].
AB  - The aim of the paper was to present symptoms and results of biochemical and
      densitometric examination in a 17-year-old girl. The girl had yolk sac tumor at
      the age of 12, in course of which she developed secondary osteoporosis.

PMID- 22384622
TI  - Heterotopic pregnancy in the absence of risk factors--diagnostics difficulties.
AB  - Heterotopic pregnancy (HP) is a rare entity occurring in 1:30000 pregnancies but
      its incidence raises as a result of assisted reproductive techniques (ART) to
      1:100-1:500. The aim of this report was to present a rare case of simultaneous
      intrauterine and extrauterine tubal pregnancy in a natural conception cycle. The
      ectopic pregnancy was not diagnosed in the first trimester scan and at 14 and 16
      weeks of gestation led to severe hemoperitoneum and two exploratory laparotomies.
      Diagnostic problems were discussed and literature was reviewed.

PMID- 22384623
TI  - [The statement of Polish Gynecological Society Experts on the etiology and
      treatment of recurrent vulvovaginal candidiasis].
AB  - Vulvovaginal infection is the most common cause of gynecological problems in
      sexually active women. Knowledge about pharmacological properties of drugs used
      in treatment recurrent vulvovaginal candidiasis allows for tailoring therapy to
      each patient. Fluconazole is modern and up to date option for treatment of
      recurrent vulvovaginal candidiasis. Short- and long-term therapeutic efficacy of
      fluconazole was confirmed in numerous high reliability clinical trials. Good
      tolerance, high effectiveness and high level of patient's acceptance gives the
      specialist powerful and efficient tool for management of recurrent Candida
      infections.

PMID- 22384624
TI  - [Body mass changes during pregnancy and concentration of insulin and neuropeptide
      Y in women with regard to the BMI].
AB  - INTRODUCTION: Obesity poses a serious problem to human population as it increases
      the risk of diabetes, hypertension, metabolic syndrome. In pregnancy obesity
      increases the frequency of its complications. AIM: The main aim of the study was
      to estimate the increase of body mass and insulin and neuropeptide Y
      concentrations in pregnant women. MATERIAL AND METHODS: The changes of body mass
      and BMI in women before pregnancy and before delivery and the concentrations of
      insulin and neuropeptide Y in blood were estimated. RESULTS: The increase of body
      mass and BMI during the pregnancy period was higher in the group with high body
      mass and I stage obesity and increase of insulin concentration depended on
      increase of the body mass. Higher concentration of NPY was found in the group of
      women with normal body mass and obese if compared to stages II and III of obesity
      No correlation between insulin increase and concentration of NPY was found.
      CONCLUSIONS: In most pregnant women body mass gain is excessive and leads to
      obesity of different stages. Insulin concentration increases as BMI increases.
      Neuropeptide Y concentration in the obese women group was lower than in the
      normal weight group.

PMID- 22384625
TI  - [Antibiotic resistance of Gardnerella vaginalis isolated from cases of bacterial
      vaginosis].
AB  - INTRODUCTION: Gardnerella vaginalis is one of the dominant etiological factors
      related to bacterial vaginosis. Literature offers a growing number of reports
      revealing there appear Gardnerella vaginalis strains increasingly resistant to
      metronidazole. OBJECTIVES: The aim of this study was to determine the
      susceptibility of Gardnerella vaginalis strains isolated from women with
      bacterial vaginosis to metronidazole, clindamycin and amoxicillin/clavulanic
      acid. MATERIAL AND METHODS: The investigation was performed on collection of 67
      Gardnerella vaginalis strains isolated from the group of 604 women participating
      in the study Antibiotic sensitivity of strains was verified by E-test method
      (BioMerieux). Interpretation of results was performed in accordance with EUCAST
      criteria. RESULTS: All tested strains, apart from one, were sensitive to
      clindamycin and amoxicillin/clavulanic acid. The results of susceptibility test
      to metronidazole indicated that 68.7% (46 out of 67 strains) were resistant to
      this antibiotic, while all of them were sensitive to both clindamycin and
      amoxicillin/clavulanic acid. CONCLUSIONS: Near future may bring the need to
      change the treatment regimen of bacterial vaginosis.

PMID- 22384626
TI  - Assessment of physician-patient trust in the obstetrics and gynecology
      departments in Poland and Greece.
AB  - AIM: To evaluate patient trust in their physicians of the obstetrics and
      gynecology departments. MATERIAL AND METHODS: We used the Trust in Physician
      Scale comprising 11-items. Data were collected from 150 women hospitalized in the
      obstetrics and gynecology departments in Poland and 109 in Greece. RESULTS: Of
      the surveyed, 25.3% from Poland and 47.4% from Greece did not doubt their
      doctors' proper care. Almost 90% of the respondents from Poland and 58.8% from
      Greece agreed with the statement "I trust my doctor very much, that is why I
      always comply with his/her advice". More than 68% of the patients from Poland and
      56.9% from Greece were convinced that "if my physician tells me something, this
      has to be the truth": Almost 77% of patients from Poland and 43.1% from Greece
      declared trust in their physicians therapy. Eighty-four percent of women from
      Poland and 49.55% from Greece were convinced that their doctor is a true expert
      in the treatment of their diseases. Nearly 97% of the patients from Poland and
      35.8% from Greece did not declare fear of their physician not keeping the
      professional secret. CONCLUSIONS: The Trust in Physician Scale is an appropriate
      tool for assessing levels of patient trust in their gynecologist. Patients
      reported a relatively high degree of trust in their gynecologists. Women from
      Greece more often than from Poland did not trust their physicians, and declared
      that doctors did not do all for their care.

PMID- 22384627
TI  - [Usefulness of osteopontin (OPN) determinations in ovarian cancer patients who
      underwent first-line chemotherapy].
AB  - INTRODUCTION: Currently CA 125 is a marker of choice for monitoring ovarian
      cancer Nonetheless, scientists are still searching for new markers, which could
      provide additional information for the evaluation of treatment, especially in
      patients with normal CA 125 levels, despite the progression of the disease.
      According to the latest reports, OPN can be a potential new marker: AIM:
      Estimation of usefulness of OPN determinations in the monitoring of ovarian
      cancer patients. MATERIAL AND METHODS: The study included 54 ovarian cancer
      patients, undergoing chemotherapy Markers were measured before, during and after
      treatment. The dynamics of the change of OPN levels was shown on line graphs,
      using Microsoft Excel programme. Statistical analysis was performed by Kaplan
      Meier method and log-rank test. RESULTS: 44% of patients from the study group
      were found to have low CA 125 levels. In these cases only the increase of OPN
      concentration indicated recurrence of the disease. In 43% of patients the high
      initial CA 125 and OPN levels decreased during chemotherapy and complete
      regression was stated in these patients. Nevertheless, in 13/17 patients a
      repeated increase of OPN concentration signalling the recurrence, earlier than CA
      125 and clinical recurrence manifestation, was observed. In 13% of patients high
      initial levels of markers did not decrease during chemotherapy which correlated
      with the progression of the disease. Our study showed that only the CA 125 levels
      had a significant influence (p=0.00063) on the disease-free survival time.
      CONCLUSIONS: Our data suggest a potential usefulness of the OPN determinations in
      estimating ovarian cancer recurrence. Nonetheless, there was no correlation
      between the initial OPN concentration and the disease-free survival time.

PMID- 22384628
TI  - Differences in the effects of beta2- and beta3-adrenoceptor agonists on
      spontaneous contractions of human nonpregnant myometrium.
AB  - OBJECTIVE: This study aimed to compare the relaxant properties of BRL 37344 with
      p2-adrenoceptors agonist ritodrine on the contractility of human nonpregnant
      myometrium. MATERIAL AND METHODS: The activity of myometrial strips mounted in an
      organ bath was recorded under isometric conditions using force transducers with
      digital output. Contractility before and after cumulative additions of both
      uterorelaxants and with preincubation with beta-adrenoceptor antagonists
      bupranolol, propranolol, and butoxamine were studied. RESULTS: Both BRL 37344
      (10(-10)-10(-4) mol/L) and ritodrine (10(-10)-10(-5) mol/L) decreased the area
      under curve, or AUC, value (log/C50 -6.45 +/- 0.18 and -8.71 +/- 0.35,
      respectively), and the degree of inhibition of spontaneous contractile activity
      was similar (< 30%). However BRL 37344 decreased the mean frequency of
      contractions, whereas ritodrine decreased the mean amplitude of contractions. The
      inhibition of contractions by BRL 37,344 was partially antagonized by bupranolol
      and propranolol, but not with butoxamine. The inhibition by ritodrine was
      counteracted by all these antagonists. CONCLUSIONS: The effects of BRL37344 and
      ritodrine on human nonpregnant myometrium are quantitatively similar in respect
      to the inhibition of spontaneous contractility yet are also distinct due to their
      substantially different influences on contraction parameters. Our data indicate
      that beta3-adrenoceptor activation is not the sole effect of BRL 37,344 on this
      tissue.

PMID- 22384629
TI  - Importance of CYP1A1 polymorphism and its transcriptional regulation in ovarian
      and endometrial cancer.
AB  - Human cytochrome P450 1A 1 is one of the most important enzymes participating in
      human carcinogenesis because it metabolites several procarcinogens to active
      carcinogenic metabolites. Additionally enzymes of CYP450 family play an important
      role in estrogenes catabolization (17-beta-estradiol and estron) to intermediate
      products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that
      catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of
      these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage
      leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract
      tissues could induce chemical carcinogenesis initiating cancer development.
      Recent studies also confirmed the role of CYP1A1 in the development of ovarian
      and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic
      variants influencing the CYP1A 1 activity could be responsible for different
      interindividual susceptibility to genital cancers in women.

PMID- 22384630
TI  - [Isolated fallopian tube torsion in a teenager--a case report].
AB  - Adnexal torsion belongs to the group of urgent cases in gynecology Early
      diagnosis and management can prevent the loss of an ovary and the Fallopian tube.
      The case of the 14.5-year-old girl was described by the authors. The symptoms
      were moderate and caused diagnostics problems. During clinical assessment current
      literature knowledge, differentiation and treatment of the adnexa were taken into
      account.

PMID- 22384631
TI  - Glassy cell carcinoma of the cervix--a case report with review of the literature.
AB  - BACKGROUND: Glassy cell carcinoma of the uterine cervix is a rare neoplasm, first
      described by Gluksman and Cherry in 1956. It is a poorly differentiated
      adenosquamous carcinoma, comprising about 1-2% of all cervical cancers. CASE
      PRESENTATION: We report a case of glassy cell carcinoma of the uterine cervix in
      67-year-old female, nullipara, diagnosed two months after symptom onset, in IV-B
      stage of the disease according to the FIGO classification scale. Cervical smear
      test obtained three years previously was normal She was offered a palliative
      antihemorrhagic radiotherapy of the pelvis and palliative chemotherapy with
      paclitaxel-carboplatin combination. The patient died within six months of
      diagnosis. CONCLUSIONS: We present a case of a rare carcinoma of the uterine
      cervix with quick progression and poor outcome.

PMID- 22384632
TI  - [Rupture of a splenic artery aneurysm in full term pregnancy--case report].
AB  - A case of a primigravida with hypovolemic shock symptoms and acute intrauterine
      fetal hypoxia was described. Emergency caesarean section, during which a
      hemorrhage to the peritoneal cavity caused by an unrecognized splenic artery
      aneurysm rupture was diagnosed, was immediately performed.

PMID- 22384633
TI  - [The statement of Polish Gynecological Society Experts on the importance of good
      hydration for the prevention of diseases in women of reproductive age].

PMID- 22384634
TI  - Clinical and histopathological factors in patients with cervical cancer allowing
      to identify candidates for less radical surgery.
AB  - OBJECTIVE: To determine clinical and histopathological factors in patients with
      cervical cancer tumors smaller than 2 cm in order to identify those who could be
      operated less extensively with preservation of reproductive organs and lower
      morbidity. MATERIAL AND METHODS: We retrospectively reviewed the records of
      patients with cervical cancer and a maximum tumor of 2cm in diameter who were
      qualified for primary surgery in the years 2001-2007 at the Department of
      Gynecologic Oncology Cancer Center in Warsaw. RESULTS: From the group of 110
      operated patients, 96 were included into the study Within the analyzed group the
      infiltration of the parametrium was found in 4 women (4.2%). All of them had
      squamous cell cancer; stage IB, grade G3. One patient had a tumor 1.5 cm in
      diameter and 3 patients had tumors up to 2 cm in diameter. The involvement of
      lymph nodes was observed in 3 patients with squamous cell carcinoma: in one case
      the tumor was intermediate grade (G2) and in two cases low grade (G3). The lymph
      nodes were involved only in patients with tumors greater than 0.5 cm. The lymph
      vascular space invasion was found in 14 patients (14.7%): in 12 with squamous
      cell cancer and in 2 with adenocarcinoma. The diameter of the tumor was 0.5-1 cm
      in 4 women, 1-1.4 cm in 3 women and 1.5-2 cm in the majority (7 women accounted
      for 29% of all patients in that group). No infiltration of the blood vessels
      could be seen in all 30 women with tumors smaller than 0.5 cm. We found a
      statistically significant relationship between the size of the tumor and the
      incidence of lymph vascular space invasion (p=0.024). CONCLUSION: In selective
      cases fertility organ preserving surgery is possible and safe. In the group of
      patients with tumor less than 5 mm in diameter no parametrium involvement or
      lymph metastases were observed. In such situation cervical conisation can be
      justified. In well-differentiated (G1) tumors less than 2 cm in diameter less
      radical surgical procedures can also be performed because no treatment failure
      has been observed.

PMID- 22384635
TI  - Expression of genes encoding for enzymes associated with O-GlcNAcylation in
      endometrial carcinomas: clinicopathologic correlations.
AB  - OBJECTIVES: O-GlcNAcylation is an abundant modification of cellular proteins
      which consist of single N-acetylglucosamine residues attached by O-linkage to
      serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of
      malignant cancer cells. The aim of the present study was to determine the
      relationship between the expression of genes encoding O-GlcNAc cycling enzymes
      (OGT and MGEAS) and clinicopathological parameters of endometrial carcinomas.
      MATERIALS AND METHODS: The mRNA expression levels of O-GlcNAc cycling enzymes in
      series of 76 samples of endometrial carcinoma were studied by real time RT-PCR
      method. RESULTS: The OGT and MGEA5 mRNA expression was significantly higher in
      tumors of higher histological grade than in well-differentiated tumors.
      Statistically significant association was found between OGT and MGEA5 mRNA
      expression and depth of myometrial invasion. Both OGT and MGEA5 expression
      profiles showed no significant association with the clinical stage of endometrial
      cancer. CONCLUSION: O-GlcNAcylation may be an important regulatory modification
      involved in endometrial cancer pathogenesis but the actual significance of this
      modification for endometrial cancer progression needs to be investigated further.

PMID- 22384636
TI  - [Fertility sparing surgical treatment of malignant ovarian tumors in the
      reproductive age group of women].
AB  - OBJECTIVE: The purpose of study is to present the pregnancies and deliveries
      after fertility sparing surgery for ovarian malignancies. MATERIAL AND METHODS:
      Medical records of outpatient and hospital treatment of patients who underwent
      primary fertility sparing surgery for ovarian malignancy were analyzed.
      Additionally we analyzed the course of pregnancy and delivery and evaluated the
      condition of neonates after delivery and during childhood with special attention
      to birth defects and malignances. RESULTS: After fertility sparing surgery for
      malignant lesions of the ovaries performed in 7 women in reproductive age, we
      noted 13 pregnancies successfully terminated with live birth and 1 case of
      ectopic pregnancy The observation period was 7-22 years. CONCLUSIONS: The problem
      of pregnancy after fertility sparing surgery for ovarian malignancy requires many
      years of observation of both the mothers and the newborns. There is a need to
      establish a nationwide register of pregnancies after fertility sparing operations
      for malignant ovarian tumors and to monitor the condition of babies delivered by
      women treated for that reason.

PMID- 22384637
TI  - Comparison of the risk factors for adverse perinatal outcomes in adolescent age
      pregnancies and advanced age pregnancies.
AB  - OBJECTIVES: To evaluate clinical outcomes of pregnancies in adolescent, advanced
      and reproductive women maternal age. MATERIALS AND METHODS: A total of 187
      pregnant women were included into the study 51 (27.27%) were adolescent
      pregnancies, mean age 17.7 +/- 3.3 years (range, 14-18 years), 40 (21.29%)
      advanced maternal age pregnancies, mean age 41.4 +/- 2.6 years (range, 39-50
      years) and 96 (51.33%), healthy controls, mean age 28.8 +/- 4.3 years (range, 19
      37 years). The majority of the adolescent pregnant women were nulliparous, while
      all of the advanced age pregnant women were multiparous (mean gravidity 4.5 +/-
      2.4; range, 6-12). Mean gravidity of the control group was 3.6 +/- 1.7 (range, 1
      12). RESULTS: There was statistically significant difference among the groups
      regarding demographic characteristics. According to the Bonferroni method, there
      was statistically significant difference among the three groups. Adverse fetal
      features were statistically different among the groups and the odd ratios were
      higher in the advanced maternal age group. The odds ratios (95% CI) for lower
      Apgar scores (Apgar score 1 and 5) and low birth weight in adolescent maternal
      age and advanced maternal age group were as follows: 1.88 (1.27-2.78) vs. 2.46
      (1.55-3.85), 2.17 (1.18-4.00) vs. 4.79 (3.02-6.69) and 1.39 (1.14-1.68) vs. 3.06
      (1.59-5.88), respectively Gestational age at birth showed minimal risk for
      adolescent age group but no risk was noted in the advanced age group.
      CONCLUSIONS: The present study showed that pregnancies in adolescent maternal
      age, advanced maternal age and reproductive maternal age are different from each
      other in terms of clinical characteristics. According to this study advanced
      maternal age pregnancies are more risky and more likely to have adverse fetal
      outcome.

PMID- 22384638
TI  - [Doppler blood flow velocimetry in the umbilical artery in uncomplicated
      pregnancy].
AB  - OBJECTIVE: To determine the resistance index (RI) and pulsatility (PI) in the
      umbilical artery (UA) in prediction of abnormal fetal heart rate during labor and
      poor fetal outcome in term pregnancy. MATERIAL AND METHODS: The study included
      148 patients at term in uncomplicated pregnancy Daily evaluation of blood flow in
      the UA was performed and PI and RI were calculated. The last value before
      delivery was taken for the analysis. In turn predictive value of Doppler
      parameters has been determined in the prediction of abnormal FHR during labor and
      abnormal newborn condition. Evaluation included fetal CTG parameters and newborn
      status based on the V.Apgar scale and acid-base equilibrium in the umbilical cord
      blood. Then selected parameters, characterizing pregnancy and the newborn status,
      with abnormal Doppler results were compared. The prognostic value of Doppler
      indices was assessed for selected parameters determining the course of pregnancy
      and abnormal fetal heart rate. RESULTS: A poor predictive value of UA PI and RI
      in the prediction of abnormal fetal heart rate during labor and poor fetal
      outcome was found. The RI in the UA presented the highest predictive value.
      CONCLUSION: RI in the UA shows higher predictive value than PI in the detection
      of abnormal fetal outcome and abnormal fetal heart rate in uncomplicated
      pregnancy at term. However, PI as well as RI in the UA have a low predictive
      value for the analyzed parameters.

PMID- 22384639
TI  - Skin hypersensitivity reactions to transdermal therapeutic systems--still an
      important clinical problem.
AB  - Transdermal therapeutic systems (TTS) belong to the widely used methods of drug
      administration, which allow rate-controlled drug delivery and avoidance of first
      pass metabolism in the liver Beside scopolamine, nitroglycerin (glyceryl
      trinitrate), nicotine, clonidine and fentanyl, also transdermal delivery of sex
      steroids for hormone replacement therapy and contraception is a well-known and
      popular method in daily clinical practice. It is estimated that approximately 20%
      of patients using transdermal estradiol may complain of adverse cutaneous side
      effects. Most of those reactions are mild or moderate, usually limited to the
      area of drug application. However, prolonged use may increase the chance of
      developing sensitization. The purpose of this review is to provide up-to date
      information on the spectrum of cutaneous reactions caused by TTS and the
      characteristics of potential contact allergens, including sex hormones. Proper
      management and prophylactic measures were also included.

PMID- 22384640
TI  - [Surgical treatment in ovarian cancer prevention in carriers of the BRCA1/BRCA2
      mutation].
AB  - Ovarian cancer remains to be a real challenge in spite of considerable progress
      in many areas of modern medicine. The use of genetic testing for detecting
      mutations of the BRCA genes has been offering clinical scrutiny between mutated
      versions of the BRCA genes and higher risk of both breast and ovarian cancer A
      population survey is a method of choice to find out more efficient screening
      management in order to identify cancer patients who further will be treated
      effectively early A review of literature on surgical PBSO (prophylactic bilateral
      salpingooophorectomy) in the BRCA genes mutations carriers with focus on
      preventive results against morbidity of ovarian cancer has been presented in the
      article.

PMID- 22384641
TI  - [Pregnancy and delivery in a patient with non-Hodgkin lymphoma--a case report].
AB  - INTRODUCTION: Neoplasmatic diseases during pregnancy are relatively rare, with
      the incidence of approximately 1/1000 pregnancies. The symptoms of neoplasmatic
      processes are unspecific and often mirror physiological changes during pregnancy
      Chemotherapy is the main therapeutic management of non-Hodgkin lymphomas. The
      strategy of the treatment and its influence on the course of pregnancy remain
      controversial. AIM: The aim of this study was to present the case of a pregnant
      woman with non-Hodgkin lymphoma. CASE REPORT: We described the case of a 27-year
      old pregnant nullipara with anemia, breathlessness, cough and general weakness
      with diagnosed diffused large B-cell lymphoma. During pregnancy the patient
      received six cycles of CHOP chemotherapy without any serious complications. On 37
      week of gestation the caesarean section was performed. CONCLUSIONS: Coexisting
      non-Hodgkin lymphomas and pregnancy are seldom the case and the treatment
      requires complex chemotherapy.

PMID- 22384642
TI  - [Symptomatic vertebral hemangioma related to pregnancy. A case report].
AB  - Hemangioma is the most common primary tumor of the spine. Pregnancy is a risk
      factor increasing the possibility of disclosure or exacerbation of symptoms of
      spinal hemangioma. This paper presents a case of 32-year-old woman with
      hemangioma of Th6 vertebrae, which was revealed by paresis of the lower limbs and
      sphincters dysfunction at 34 weeks gestation. Pregnancy has ended with a cesarean
      section. Then posterolateral thoracotomy and removal of hemangioma were
      performed. Spinal cord was decompressed and stabilization of the spine with metal
      implants was carried out. Histological examination discovered cavernous
      hemangioma weaving. The patient is followed up in the outpatient clinic. Despite
      the improvement of neurological status--enhancement of the sensory function and
      development of bladder and rectal sphincter automatism--she did not regain the
      ability to walk alone.

PMID- 22384643
TI  - [Penile cancer--case report and literature review].
AB  - Penile cancer occurs quite seldom, mostly in men around 60 years of age. However
      penile squamous cell carcinoma is also observed in younger men. Etiology remains
      unclear but we can recognize some risk factors such as poor hygiene for example.
      The authors report a case of a patient who refused treatment in early stages of
      the disease and was treated only after disease progression. Applied surgical
      treatment, unfortunately proved to be insufficient and the patient was
      transferred to complete therapy at the oncology department. This case inspired us
      to recall the basic diagnostic and therapeutic methods used at the time of
      diagnosis of the penile tumor

PMID- 22384644
TI  - [Expert panel recommendations Polish Gynecological Society for preparations
      Femibion Natal 1, Femibion Natal 2 and Femibion Vita Ferr].

PMID- 22384645
TI  - [Recommendations of the Polish Gynecological Society Expert Committee regarding
      application of progesterone in obstetrics and gynecology].

PMID- 22384646
TI  - Microcirculation patterns in indocyanine green angiography and the results of
      plaque therapy in choroidal melanoma.
AB  - PURPOSE: To determine the effect of radioactive plaque therapy on blood vessel
      behaviour in choroidal melanomas using indocyanine green (ICG) angiography.
      MATERIAL AND METHODS: Fifty-five patients with choroidal melanoma were studied.
      Ruthenium-106 plaques were used in 30 eyes, in 11 the "sandwich method"
      (Ruthenium-106 plaque with transpupillary thermotherapy), was applied and 14
      tumours were treated with Iodine-125. In all cases ICG angiography was performed
      prior to treatment and 12 months after, and at different time afterwards.
      Baseline tumour microcirculation patterns (MCPs) were studied prior to treatment
      and post-treatment blood vessels changes were evaluated. Total follow-up period
      ranged from 14-22 months (mean: 16 months). RESULTS: Pre-treatment ICG
      angiography revealed complex MCPs, combining parallel with cross-linking, arcs
      with branching, loops and networks patterns in 23 (41.8%) and non-complex MCPs,
      including straight, parallel without cross-linking and arcs without branching
      patterns in 32 (58.2%) melanomas. Twelve months after treatment, 38 tumours
      (69.1%) showed a significant changes in their MCPs. The mean ultrasonographic
      regression rate in tumours with complex MCPs was 57.4% as opposed to 36.2% in the
      group with non-complex MCPs (p = 0.01). No statistically significant correlation
      in the height regression rate was found among the various methods of therapy,
      however a significant difference between the type of therapy and MCPs changes was
      observed (p < 0.001). Melanomas treated with Ruthenium-106 and TTT demonstrated
      slight or no MCPs changes, while tumours treated with Ruthenium-106 and Iodine
      125 plaques alone showed a significant MCPs changes (p < 0.001). The statistical
      analysis showed the correlation between the type of baseline MCPs and the degree
      of their changes after treatment (p < 0.001). Tumours with networks, loops, arcs
      with branching and parallel with crossing showed an increased regression as
      compared to other MCPs. Twelve patients whose tumours contained complex MCPs
      developed metastatic disease. CONCLUSIONS: This study suggests that the response
      of choroidal melanoma to irradiation is related to MCPs as identified by ICG
      angiography; the presence of complex MCPs is associated with a high regression
      rate after plaque therapy and a high risk of development of systemic metastatic
      disease.

PMID- 22384647
TI  - Evaluation of surgically induced astigmatism after coaxial phacoemulsification
      through 1.8 mm microincision and standard phacoemulsification through 2.75 mm
      incision.
AB  - Improvements in technology connected with cataract surgery have made it possible
      to decrease significantly the size of corneal incision created during
      phacoemulsification. Recently, coaxial phacoemulsification through a 1.8 mm
      microincision (C-MICS) has been introduced. This technique is perceived as the
      next step in development of phacoemulsification. PURPOSE: To compare surgically
      induced astigmatism (SIA) after coaxial 1.8 mm microincision cataract surgery (C
      MICS) and standard phacoemulsification through 2.75 mm incision, calculated with
      three mathematical methods. MATERIAL AND METHODS: A consecutive, prospective
      series of 55 eyes of 55 patients who underwent uneventful C-MICS with foldable
      IOL implantation using 1.8 mm temporal clear corneal incision were included in
      group 1. Reference group (group 2) included 55 eyes of 55 patients who underwent
      uneventful phacoemulsification through 2.75 mm temporal clear corneal incision
      with a foldable IOL implantation. SIA was calculated using three methods.
      RESULTS: All patients had uneventful surgery and were examined before the surgery
      and one month postoperatively. There was a significant postoperative increase in
      corrected distance visual acuity in both groups (p < 0.01), and the visual
      outcomes in both groups were similar (p > 0.05). In vector analysis, mean SIA was
      0.42 +/- 0.30 in group 1 and 0.77 +/- 0.55 in group 2. In vector decomposition,
      the mean SIA (C90) in group 1 was 0.24 +/- 0.29 and 0.49 +/- 0.54 in group 2 (p <
      0.05). In Naeser's polar values method, deltaKP-0 was -0.06 +/- 0.43 in group 1
      and -0.21 +/- 0.84 in group 2 (p > 0.05). CONCLUSIONS: 1.8 mm coaxial MICS
      induces a significantly smaller value of SIA than standard 2.75 mm
      phacoemulsification.

PMID- 22384648
TI  - [Endonasal microscopic surgery of the lacrimal duct stenosis--long-term results].
AB  - AIM: The value of a complex endonasal microsurgical treatment of lacrimal duct
      stenosis. MATERIAL AND METHODS: in a group of 418 patients we performed 455
      dacryocystorhinostomy (DCR) including 37 bilaterally. They were 263 females
      (62.9%) and 155 males (37.1%). Age ranged from 1.5 to 87, mean age 54.3 years.
      Performance: general anaesthesia with controlled hypothension, semi sitting
      position of patient and adjustable headrest, operating microscope (300 mm lens).
      Operative procedure: septum mobilization and anterior ethmoidectomy,
      dacryocystorhinostomy (DCR). RESULTS: satisfactory results were obtained in 436
      of cases (95.8%), 19 no change (4.2%). Only 18 cases received a prosthesis. There
      were only 2 complications (0.2) not serious. CONCLUSION: endonasal microscopic
      dacryocystorhinostomy preserves intact bony support and frame of lacrimal ducts
      and the nasal function of the lacrimal pump. It allows simultaneous management of
      the concomitant sino-nasal pathology as well as shorter operation times, lower
      complication rates and reduced patient morbidity.

PMID- 22384649
TI  - [Fundus autofluorescence in eyes with dry and wet form of age-related macular
      degeneration (AMD)--clinical implications].
AB  - PURPOSE: To evaluate retinal pigment epithelium (FIPE) and photoreceptors layer
      integrity in different stages of AMO based on fundus autofluorescence imaging and
      to correlate autofluorescence images with visual acuity. MATERIAL AND METHODS:
      322 eyes of 200 patients with different forms and stages of AMD were studied.
      Mean age was 70 years (49-91 years). Apart from complete ophthalmologic
      examination patients were examined every 6 months by using a confocal scanning
      ophthalmoscope HRA2. Follow-up period ranged trom 1 to 40 months (mean--18
      months). RESULTS: In 116 eyes with early AMO punctuate changes in
      autofluorescence images were observed while in 22 eyes (16%) no distinct changes
      were present. In 52 eyes (62%) with wet AMD normal or near normal
      autotluorescence signal was present and 34 eyes (38%) with wet AMO had changes in
      autofluorescence signal corresponding with choroidal neovascularisation (WV)
      area. In the group of eyes with autofluorescence changes in the CNV area median
      BCVA was 0.1 and in the group without autofluorescence changes within the CNV
      area--0.4. All eyes with disciform scar were characterized by uneven
      autofluorescence signal decrease in scar area with increased signal in surroundig
      area. Eyes with geographic atrophy (GA) had lack of autofluorescence signal
      corresponding to RPE atrophy and in 40 cases (95%) increase autofluorescence
      signal junctional to GA was noted. CONCLUSIONS: Fundus autofluorescence images of
      the AMO eyes varies greatly. Decrease of autofluorescence signal correlates with
      visual acuity decrease.

PMID- 22384650
TI  - [Surgical management of suprachoroidal haemorrhages induced by cataract surgery-
      case series].
AB  - PURPOSE: Suprachoroidal hemorrhage (SCH) is a rare complication occurring during
      surgery (early SCH) or 3-5 days after operation as a delayed suprachoroidal
      hemorrhage. It occurs more often in patients who have complicated cataract
      surgery with vitreous loss or lens dislocation. The purpose of this study was to
      present surgical treatment of 7 patients with suprachoroidal hemorrhage due to
      cataract surgery. MATERIAL AND METHODS: Mean age of patients was 72,4 years old.
      There were 3 female and 4 male. Six patients were operated using
      phacoemulsification, one patient- using ECCE. In 3 cases the vitreous loss and
      lens dislocation occurred during operation. RESULTS: Suprachoroidal drainage was
      performed in 4 patients. In 3 patients suprachoroidal drainage was followed by
      vitrectomy. In this group in 2 patients injection of silicone oil was done.
      Anterior infusion line was used in all cases. Drainage sclerotomies were created
      in the quadrants of the involved SCH, confirmed by ultrasonography. In all
      treated patients reattachment of the choroid was obtained. The visual acuity
      improved significantly (final v. a. was between 0. 02 and 0. 5). CONCLUSIONS:
      According to our observation, the implementation of the suprachoroidal drainage
      combined with vitrectomy might improve the prognosis and facilitate the
      achievement of functional vision.

PMID- 22384651
TI  - [Level of selected antibacterial tear proteins in children with diabetes type 1].
AB  - PURPOSE: Antibacterial immunity in diabetes is impaired, which increases the risk
      of general and local infections. The aim of the study was to evaluate non
      specific local antibacterial immunity based on lactoferrin and lysozyme
      concentration in tears in children with diabetes type 1. MATERIAL AND METHODS:
      Children at the age of 10-18 years old were studied. Group 1. consisted of
      children without diabetes, group 2. included patients with new onset of diabetes
      and group 3. consisted of children with decade-long diabetes. Among all patients
      tears were collected from inferior coniunctival fornix with hematocrit glass
      capillaries in purpose to measure lactoferrin and lysozyme concentration. ELISA
      method was used in laboratory testing. RESULTS: Level of lactoferrin did not
      differ significantly among all groups. Concentration of lysozyme was
      statistically lower in group with decade-long diabetes (group 3.) compared to
      patients without diabetes. Mild correlation between lactoferrin and lysozyme
      levels was seen in individual patients in whole group of probands together.
      CONCLUSIONS: Diabetes type 1 in children is associated with significant changes
      in concentration of tear proteins, which contribute to antibacterial immunity.

PMID- 22384652
TI  - [Age-related macular degeneration (AMD)--primary results "Bus-Tour'2011" action].
AB  - PURPOSE: The aim of article is to sum up "Bus-Tour'2011" action concerning age
      related macular degeneration (AMD). MATERIAL AND METHODS: Between March 29 to May
      28.2011 in 10 polish cities 7292 persons were examined. The ophthalmological
      examination were done in special bus with diagnostic equipment (Bausch & Lomb
      owner). RESULTS: In almost 19% (1355 persons), changes in eye fundus as age
      related macular degeneration were found. Additionally in 324 persons (4,4%),
      ophthalmologists found some high suspicious AMD changes. CONCLUSIONS: Knowledge
      about AMD in polish population is very poor.

PMID- 22384653
TI  - Application of autologous cultivated corneal epithelium for corneal limbal stem
      cell insufficiency--short-term results.
AB  - PURPOSE: To present results of ocular surface reconstruction with application of
      cultured corneal epithelium in limbal stem cell insufficiency. MATERIAL AND
      METHODS: 25 patients suffered from limbal insufficiency in one eye after a
      chemical or thermal burn. Their healthy eyes were the source of limbal epithelium
      for corneal epithelial culture. Limbal cells from a 2 mm2 biopsy were seeded on
      amniotic membrane. Cultures were carried out in standard conditions in
      supplemented DMEM in presence of 3T3 fibroblasts. After superficial keratectomy
      the amniotic carriers with epithelial cells were transplanted on denuded corneas.
      The presence of corneal vascularization, epithelial regularity and visual acuity
      were evaluated. RESULTS: Postoperative follow-up ranged from 3 up to 9 months,
      average 4.9 +/- 1.1 months. 3 months after the surgery 72.0% of the eyes showed
      stable epithelium with slight corneal haze caused by the amnion. In 60.0% of the
      eyes there was no recurrent conjunctival neovascularization. 28.0% of the eyes
      remained cloudy due to stromal revascularization. In 2 eyes total conjunctival
      pannus developed again. Visual acuity ranged from counting fingers to 0.6.
      CONCLUSION: Transplantation of cultured epithelium is a promising method in
      treatment of limbal stem cell insufficiency giving satisfactory restoration of
      corneal epithelium.

PMID- 22384655
TI  - [Persistent fetal vasculature syndrome--clinical image and diagnostic
      difficulties].
AB  - PURPOSE: The aim of this review is to present cases of clinically differentiated
      picture of persistent fetal vasculature syndrome--PFVS (also called persistent
      hyperplastic primary vitreous body--PHPVB) observed in group of infants and
      children. MATERIAL AND METHODS: Case records of four children with characteristic
      changes of posterior form of persistent fetal vasculature syndrome, which were
      observed on fundus of the eyes, were analyzed retrospectively. Routine
      ophthalmological examination, genetic, cytogenetic and laboratory tests towards
      coexisting bacterial, viral and parasitic diseases and congenital anomaly of the
      eye or chorioretinal neoplastic changes of neonatal period were performed.
      Ophthalmological changes were archived using Ret-Cam II apparatus (Clarity
      Medical Systems). Measurement of the axial diameter of the eyes and exclusion
      coexisting ocular disease by ultrasonography (A-scan US i B-scan US and color
      Doppler ultrasonography--CDU), were performed. RESULTS: Different clinical image
      of posterior form of persistent hyperplastic primary vitreous body was observe in
      ophthalmological examination. Changes such as fibrovascular tissue connecting
      optic disc (n. II) with ora serrata of the retina coexisting with retinoschisis,
      retrolental mass or persistent hyaloid artery were observed. Additionally
      concomitant features in pathological eyes were: iris hypoplasia, corectopia,
      microphthalmia, congenital cataract, secondary glaucoma, degeneration or
      retinoschisis and intrvitreous haemorrhage. Strabismus, nystagmus and heart
      disease in the form of persistent fetal circulation were associated with
      ophthalmological changes. Inflammatory and genetically determined diseases were
      excluded in differential diagnosis. CONCLUSIONS: The diagnosis of persistent
      hyperplastic primary vitreous body (PHPVB) was confirmed by characteristic
      clinical symptoms and results of the additional research. Suggestion of
      recognition of this syndrome (PHPVB) as well as persistent fetal vasculature
      syndrome (PFVS) should be implemented diagnostics towards other optic and
      systemic development defects.

PMID- 22384654
TI  - Chorioretinitis in infants.
AB  - PURPOSE: The aim of this review is to present cases of chorioretinitis in infants
      caused by viral and parasitic infections. MATERIAL AND METHODS: Four infants with
      viral chorioretinitis were identified in a routine ophthalmological examination.
      Laboratory tests towards bacterial, viral and parasitic diseases were performed.
      RESULTS: Toxoplasmosis, rubella, and CMV infections were diagnosed in clinical
      and laboratory tests. After a wide spectrum of therapy a total remission of
      inflammatory process in all the discussed children was observed. CONCLUSIONS:
      Posterior uveitis is an ocular complication which can be connected with viral or
      parasitic infections in postnatal period. Prematurity, normal delivery,
      intrauterine transmission, breast feeding, comorbid diseases might be associated
      with chorioretinitis in infants.

PMID- 22384656
TI  - [Congenital pit of the optic nerve head with maculopathy--a case report].
AB  - The aim of the article is to present the case of a fifty years old man suffering
      from congenital pit of the optic head with remission confirmed by OCT
      examination. The diagnosis was established after indirect ophtalmoscopy and OCT.
      Congenital pit of the head is a rare anomaly caused by the mutation of a PAX 2
      gene. Location of the pathology and its symptoms cause difficulties in diagnosis
      and may indicate central serous choroidoretinopathy or glaucoma. Modern and non
      invasive techniques show a two-layer structure at the edge of corpus vitreum and
      retina. Confirmation of congenital pit of the optic head has a prognostic value
      with other diseases of retina, such as hole of macula. Only 25% of cases have
      symptoms of remission without treatment. The rest require further monitoring and
      various methods of treatment, including vitrectomy.

PMID- 22384657
TI  - [Choroidal melanoma treatment by endoresection].
AB  - PURPOSE: To report choroidal melanoma treatment by endoresection. MATERIAL AND
      METHODS: A retrospective review of a series of 2 patients with choroidal melanoma
      that did not meet the criteria for brachytherapy. Both patients were treated by
      tumor endoresection supported by brachytherapy. Outcome measures included
      preoperative and postoperative visual acuity at 1, 3, 6 months. Preoperative
      evaluation included tumor measurements in ultrasound. Systemic evaluation (liver
      function test, chest x ray, abdominal ultrasound), was carried out to monitor
      possible metastases in the observation period. RESULTS: The two operated patients
      were followed-up for 6 months. Visual acuity deteriorated from 5/16 (0.51 logMAR)
      preoperatively to 5/25 (0.7 logMAR) postoperatively in patient 1, and improved
      from 3/50 (1.22 logMAR) do 5/25 (0.7 logMAR) in patient 2. This corresponded to
      deterioration by 0.19 logMAR and improvement by 0.52 logMAR respectively. Neither
      tumor recurrence nor metastases were detected in the follow-up period.
      CONCLUSIONS: Endoresection is a treatment option, alternative to enucleation,
      that can conserve the eye It sometimes can be performed in eyes that are not
      eligible for trans-scleral resection. Further larger studies are needed to
      establish the efficacy of this still controversial surgery.

PMID- 22384658
TI  - Bilateral spontaneous dislocation of IOLs within the capsular bag to the anterior
      chamber in a retinitis pigmentosa patient.
AB  - PURPOSE: The aim of the paper is to present a case of 82 year old man suffering
      from retinitis pigmentosa, who over the period of 10 years developed partial,
      bilateral spontaneous dislocation of IOLs within the capsular bag to the anterior
      chamber. MATERIAL AND METHODS: Complexes of IOLs in the capsular bags with severe
      capsule contraction were removed and AC IOLs were implanted in both eyes.
      RESULTS: Vision improved significantly in both eyes. CONCLUSIONS: Reported
      complications can be related to coexisting retinitis pigmentosa in described
      patient.

PMID- 22384659
TI  - Emerging therapies for the treatment of wet age-related macular degeneration-
      VEGF Trap-Eye.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      industrialized world. The most severe form of this disease is exudative AMD. It
      accounts for 10% of cases of AMD and is responsible for approximately 90% cases
      of severe vision loss due to AMD. Anti-vascular endothelial growth factor (VEGF)
      therapy changed the standard-of-care for this blinding disease. This article
      presents one promising new drug for the treatment of exudative AMD--VEGF Trap
      Eye.

PMID- 22384660
TI  - [Neuroadaptation and quality of vision].
AB  - PURPOSE: The aim of this article is to introduce and elaborate upon
      neuroadaptation and quality of vision in the available literature. MATERIAL AND
      METHODS: The information contents in the article comes from several studies in
      literature performed on groups of patients with different forms of aberrations
      and neuroadaptation problems. Visual quality and satisfaction in the most of them
      were very poor. RESULTS: After surgical treatment--corneal or intraocular, most
      of patients were highly satisfied. Photorefractive keratectomy and/or lens
      surgery using diffractive multifocal lenses gave decrease optical ocular
      aberrations and improve quality of vision and life. CONCLUSIONS: Based on current
      literature decrease of ocular aberrations gives better neuroadaptation and in
      consequence improves quality of vision and life. To establish these data, further
      studies on representative group of patients are necessary.

PMID- 22384661
TI  - [Molecular investigation of enteroaggregative, shiga toxin-producing E. coli
      O104:H4 isolated in Poland during the recent international outbreak-
      characteristic of epidemic clone].
AB  - Since early May 2011 a large food-borne outbreak caused by E. coli O104:H4
      affected Germany then spread over 13 European countries, U.S.A. and Canada. The
      outbreak strain was found to possess an unusual combination of enteroaggregative
      E. coli pathotype with StxII. In this report we described the molecular
      investigation of epidemic clone in Poland during the international outbreak. We
      confirmed three cases of E. coli O104:H4 infections. The molecular
      characteristics of the Polish E. coli O104:H4 isolates including virulence
      profile, antimicrobial resistance, PFGE and plasmids profiles were corresponded
      with Germany outbreak strains.

PMID- 22384663
TI  - [Analysis of the genetic background and mechanisms of dissemination of resistance
      to tetracycline of the Polish population of Campylobacter strains isolated in
      Poland in years 2007-2008].
AB  - In Poland, constant rise of number of Campylobacter strains resistant to
      tetracycline is observed in Poland. Analysis of the resistant strains showed
      their strong diversity, including both the different levels of resistance to this
      drug, large differences in the sequence of the resistant gene tetO, and diverse
      phylogenetic origin. The study also confirmed the important role of horizontal
      spread of resistance which, in the event of such a large diversity of resistant
      strains, can cause further very rapid escalation of resistance of Campylobacter
      to tetracycline.

PMID- 22384662
TI  - [Evaluation of usefulness of the enzyme-linked immunosorbent assay (ELISA) for
      the detection of antibodies to lipopolysaccharides of VTEC strains in patients
      suspected for Escherichia coli O104:H4 infection in Poland].
AB  - The aim of the study was to investigate the presence of antibodies to
      lipopolysaccharides obtained by modified Boivin's method from E. coli serotype
      O104:H4 and O26, O103, O111, O121, O145, O157 in sera of 7 patients with acute
      diarrhea, suspected in clinical investigation for infection caused by E. coli
      O104:H4. Additionally, to determine the cut-off levels, the 75 sera from blood
      donors were tested. The high level of antibodies to LPS E. coli O104 was
      diagnosed in three patients from family outbreak caused by E. coli serotype
      O104:H4. In one of those patients, 7-years boy with HUS, we observed also a
      significant decrease of level of IgA, IgG and IgM antibodies in serum sample
      obtained in chronic phase of the disease. Furthermore, we showed that two others
      patients with clinical evidence of VTEC infection, not connected with this family
      outbreak, had a high level of antibodies to E. coli of other serotypes: one to
      O157 and one to O103. We did not observe presence of antibodies to LPS from E.
      coli O26, O111, O121 i O145 in the sera of tested patients. In conclusion, we
      confirmed that ELISA based on lipopolysaccharides obtained from different
      serotypes of E. coli may be helpful in laboratory diagnosis of infection caused
      by VTEC in humans.

PMID- 22384664
TI  - [Comparison and evaluation of the Binax EIA and Biotest EIA urinary antigen kits
      for detection of Legionella pneumophila antigen in urine samples].
AB  - The Binax and the Biotest urinary antigen kits for detection of L. pneumophila
      antigen were compared by testing of selected 67 urine samples obtained from EWGLI
      as reference samples in External Quality Assessment Scheme. Thirty nine were
      positive with the Binax kit (100% of sensitivity), and 33 were positive with the
      Biotest (84.6% of sensitivity). The test specificities were 100% for the both
      kits. It was concluded that the Binax kit was more suitable for the routine
      diagnosis of Legionella infections than the Biotest kit.

PMID- 22384665
TI  - [Evaluation of molecular biology reagents used in plcR-tergeted RSI-PCR assay for
      B. anthracis identification and their influence on time necessary for obtaining
      results].
AB  - Fast and reliable identification of B. anthracis is crucial for a successful
      therapy of persons exposed to anthrax spores. Use of molecular biology techniques
      significantly reduces time necessary for obtaining results. However, the
      molecular identification is hampered by the high genetic similarity of the B.
      cereus group bacteria. A lot of published B. antharcis identification approaches
      turned out to be non-specific. Nevertheless, theplcR-targeted RSI-PCR assay
      described in 2007 is still regarded as highly specific for anthrax
      identification. In this paper possibility of significant reduction of time
      necessary for obtaining results by the use of modern, "fast" polymerases and
      restriction enzymes will be presented. The use of a such reagents enable to
      reduce time of the plcR-targeted RSI-PCR assay to about two hours.

PMID- 22384666
TI  - [Assessment of essential oils activity used in liquid or volatile phase against
      biofilm cultures of Staphylococcus aureus and Candida albicans. The
      methodological study].
AB  - Biofilm formation is a significant factor in chronic infections with fungal and
      bacterial pathogens. Due to the high drug resistance of biofilm populations and
      the frequent failures of chemotherapy i such infections, it seems necessary to
      take recourse to unconventional treatment methods involving e.g. the use of some
      phytocompounds such as essential oils or their components. In order to evaluate
      the effect of their action on the microbial biomass a variety of techniques are
      used. However, there is still a need to develop new tests or modifications of
      these known, for the biofilm viability assessment. They should be adapted to the
      physico-chemical nature of the tested compounds and should decrease the risk
      ofbiofilm damage during staining procedure. We described a test assessing the
      effect of essential oils on bacterial and fungal biofilm formed on the membrane
      of cell culture inserts. The proposed model provides a minimal violation of the
      biofilm integrity during the test. It allows easily explore the activity of
      essential oil volatile fraction and is useful in determination of the kinetics of
      their action. Using this test it is also easy to examine the relationship between
      antimicrobial activity and the cytotoxic effect, known as the biocompatibility
      index (BI, biocompatibility index). Moreover, it allows qualitative and
      quantitative analysis of metabolic products, released into the growth medium from
      biofilm's cells. In successively repeated experiments high reproducibility of
      results has been obtained, thus the developed methodology seems to be useful in
      our future studies in this field.

PMID- 22384667
TI  - [Pathogens isolated from patients with community-acquired lower respiratory tract
      infections].
AB  - The aim of the study was to assess the prevalence and antimicrobial
      susceptibility of pathogens in patients hospitalized in Clinic of Pneumology and
      Alergology University Clinical Hospital No 1 in Lodz in 2006-2008 period, due to
      community-acquired lower respiratory tract infections. In this samples of sputum,
      bronchoaspirate and BAL's were evaluated. The most frequent pathogens isolated
      from all examinated patients were Gram-negative rods. This bacteria were
      susceptible in most to imipenem (91%), ceftazydym (71%), amikacin (67%),
      ciprofloxacin (63%) and to amoxicillin with clavulanic acid only in 18%. This
      study show high prevalence of Gram-negative rods in patients hospitalized due to
      community-acquired lower respiratory tract infections.

PMID- 22384668
TI  - [Effect of storage conditions of clinical materials on virological tests results
      by RT-PCR].
AB  - Obtaining a reliable laboratory test result depends on many factors, among which
      preanalitical factors play a significant role. The aim of this study was to
      determine the effect of temperature, storage time of samples and number of
      freezing and thawing cycles on the results of tests carried out by RT-PCR. The
      study was conducted in a model of measles virus (RNA). The results revealed that:
      (1) Samples of clinical material (serum, cerebrospinal fluid, urine) for testing
      by RT-PCR can be stored for at least 5 days at room temperature or refrigerated
      and at least 7 days when frozen, (2) Freezing and thawing three times, samples of
      clinical material does not affect the outcome of the presence of viral RNA, (3)
      Isolated viral RNA is stable at freezer temperature and can be subjected to at
      least 20 freeze-thaw cycles without affecting the results.

PMID- 22384669
TI  - [Toll-like receptors expression on Burkitt lymphoma cells].
AB  - Toll like receptors (TLRs) are an important component of the immune response.
      They are link between innate and adaptative response. Lymphocytes B express most
      of the toll-like receptors and they may respond to a broad spectrum of PAMP.
      Lymphocytes B are one of the major lymphocyte populations in secondary lymphoid
      tissues, where they represent up to 50% of cells population. These cells are an
      important element of the defense, largely by using the mechanisms associated with
      innate response. On the other hand, lymphocytes B are the site of EBV latency, so
      Burkitt lymphoma cells can may be a convenient model to study the mechanisms
      associated with EBV infection. The aim of study was to determine the expression
      of TLRs at the m-RNA level of in Burkitt lymphoma cells treated with ligands for
      selected TLRs. P3HR, Raji and Namalwa cells were stimulated with Pam3 (10
      microg/ml), PolyI:C (25 microg/ml), LPS (10 microg/ml) and measles virus (MeV,
      moi 0.02). Unstimulated cells and cells treated with PMA (0.5 microg/ml) served
      as negative and positive controls. After incubation, from stimulated and
      unstimulated cells mRNA was extracted, RT-PCR reaction was performed and
      electrophoretic separation was made. The intensity (INT) of bands were determined
      using the tools for quantitative analysis. In order to analyze the expression of
      TLR genes, INT values for TLR2, TLR3 and TLR4 in tested cell lines are expressed
      as %, assuming an average level of GAPDH expression as 100%. The 25% of INT for
      negative control was accepted as a change in expression level. It was found that
      the expression of Toll-like receptors in Burkitt lymphoma cells is diverse both
      in terms of cell type and the type of stimulation.

PMID- 22384670
TI  - [Network activity of "interneurons" and large cells of amygdala in active and
      passive rabbits].
AB  - By plotting cross-correlation histograms differences were found in interaction of
      conjectural small "interneurons" and large principal cells of the central and
      basal amygdalar nuclei in negative emotional situations. The network activity of
      "nterneurons" was higher than in principal cells. "Interneurons" more frequently
      had excitatory and inhibitory input or output connections with neighbouring
      cells, latency of their connections with other cells was smaller than in
      principal neurons. Interaction of "interneurons" and principal cells differed in
      animals with active and passive behavioural strategy in negative emotional
      situations. As compared to active animals, in passive rabbits inhibitory
      connections to "interneurons" from other cells occurred more frequently,
      excitatory or inhibitory connections from "interneurons" to principal cells
      appeared more rare.

PMID- 22384671
TI  - [Physiological analysis of various types of osmotic diuresis].
AB  - Efficacy of drugs reduced proximal reabsorption was compared in experiments with
      female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced
      after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold,
      exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal
      values of Na+ excretion were observed during Na2SO4 and exenatide administration
      (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion
      was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs.
      7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3
      micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were
      additive after combined administration of maximal doses of exenatide and PEG
      which suggests a different mechanism of action of solutes filtrated (PEG) to the
      proximal nephron segment and generated due to Na+/HW-exchange inhibition
      (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action
      and selectivity of ion excretion).

PMID- 22384672
TI  - [The role of histamine in regulation of spontaneous electrical activity of the
      rat ureter and bordering to bladder area].
AB  - The nature of the influence of histamine on the slow wave and spike spontaneous
      activity of both perirenal and peribladder bordering areas of the bladder zone
      has been studied. It is shown that under these conditions of activated renal
      section of the organ, in the distal part, the decrease in frequency of the slow
      waves occurred. The histamine effect also contributes to improvement of the
      conduction of the excitation wave propagating to the bladder, which destroys the
      coordination of spike activity of the latter with slow waves of ureteral
      bordering zone.

PMID- 22384673
TI  - [Analgesic effect of corticotropin-releasing factor administered into midbrain
      periaqueductal grey matter].
AB  - Corticotropin-releasing factor (CRF) participates in development of stress
      induced analgesia. Midbrain periaqueductal grey matter (MPAG) is one of crucial
      structures of the brain antinociceptive system. The aim of the study was to
      investigate effects of the CRF administration into the MPAG on pain sensitivity
      in alert rats and contribution of opioid mechanisms to these CRF-induced effects.
      Somatic pain sensitivity was tested by tail flick response latency following
      thermal stimuli. The opioid antagonist naltrexone administered systemically or
      centrally into the MPAG was used to study involvement ofopioid mechanisms in the
      CRF-induced effects. The CRF administration (0.7 microg/rat) into the MPAG caused
      analgesic effect. The CRF-induced analgesic effects were eliminated by systemic
      as well as central naltrexone pretreatment. Effect of central naltrexone on the
      CRF-induced analgesia manifested itself faster as compared with effect of
      systemic naltrexone. The data obtained suggest that one of central mechanisms of
      the CRF-induced analgesic effect on somatic pain sensitivity in alert rats may be
      mediated by the MPAG neurons and provided by involvement of opioid mechanisms.

PMID- 22384674
TI  - [Responses of neurons of the solitary tract nucleus to noxious colorectal
      distension in rats].
AB  - In experiments on anaesthetized rats, the neuronal mechanisms underlying
      processing of the nociceptive information from the colon within the nucleus of
      the solitary tract were studied. In addition, the role of nitric oxide in these
      processes was estimated. Analysis of changes in c-fos expression revealed that
      nociceptive colorectal distension (CRD) resulted in activation of neurons mainly
      in the medial, commissural, parvicellular and dorsomedial subnuclei of the
      solitary tract nucleus. Non-noxious CRD evoked in these subdivisions weak phasic
      excitatory neuronal responses. Under noxious CRD, neurons with phasic (58%) and
      tonic (42%) responses were revealed. The phasic neuron responses were
      significantly enhanced in comparison with non-noxious CRD. Inhibition of the
      neuronal NO-syntheses resulted in significant decrease of neuron responses to
      noxious CRD and the number of cells with tonic reactions. Therefore, neurons with
      tonic responses may be directly related to NO-depended processing ofnociceptive
      information from colon.

PMID- 22384675
TI  - [Dependence of organism stability on chronic stress from thyroid status].
AB  - In experiences on 108 male rats, the effect of acute (immobilization during 3
      hrs) and chronic (immobilization for 3 hrs during 5 days) stresses on the
      organism general stability was studied as evaluated with changes of body weight,
      adrenal glands, spleen, thymus relative mass, gastric mucosa state, animals
      physical endurance. Chronic stress evoked more obvious decreasing of spleen and
      thymus relative mass than the acute one, as well as lesion of gastric mucosa
      accompanied with decrease of the rat resistance to physical loading. Thyroid
      function suppression by merkazolil (1.2 mg/100 g body weight during 14 days)
      promotes further the reduction of the organism stability in acute and,
      especially, in chronic stress, while physiological doses of thyroid hormones (5.0
      8.0 mcg of thyroxin on kg of body weight during 28 days), on the contrary,
      increased it in both stress conditions. Existence of the organism stability
      dependence on thyroid status both in acute and chronic stress proves
      iodothyronine's important role in the organism antistress-system.

PMID- 22384676
TI  - [Effect of volatile excretions induced with thymus-dependent antigen in female
      mice on the behavioural responses of males].
AB  - It was found that thymus-dependent antigen sheep red blood cells in the optimal
      immunogenic dose (1 x 10(8) cells/mouse) induced in female mice of CBA and B6
      strain secretion of attractive urinary volatile components (VCs), and in the
      supraoptimal dose (1 x 10(9) cells/mouse)--aversive VCs for intact males CBA
      strain. In a direct comparison of the properties ofVCs-immunized mice of CBA and
      B6, a modification of the effect of constitutive chemosignalling: disturbance of
      ability of females VCs to attract allogeneic males, was observed. The role of
      thymus-dependent antigen dose and sex of animals in the mechanism of generation
      of antigen-induced chemosignals is discussed.

PMID- 22384677
TI  - [Blood flow in the brain and liver of chicken in embryonal and early
      postembryonal periods].
AB  - In chicken Leghorn, blood flow volume speed (BF, laser-Doppler flowmetry) in the
      brain hemispheres and in liver was measured on days 10, 14, and 19 of
      embryogenesis and on day 4 after hatching (in experiments on late embryos and
      chickens, urethane narcosis was used). It was revealed, that initial BF in
      investigated organs was 2-fold lower than earlier measured in skeletal muscles.
      In the liver, low BF remained at all periods, but it grew 5-fold greater after
      hatching. In the brain hemispheres, the BF during this period grows gradually
      reaching 4-fold size in chickens. It was shown that blood stream increase in the
      brain was accompanied by uniform increase in anatomic lumen of internal carotid
      artery; thus settlement sizes of linear speed of blood flow and wall shear stress
      remain in it at the same level. Lumen extension of celiac artery during the
      observation period lags behind increases in a blood stream of in it that leads to
      increase in it of the named parameters.

PMID- 22384678
TI  - [Pavlov Department of Physiology: 120 years of scientific research].

PMID- 22384679
TI  - [Investigation of causes of the conflict between taxonomy and molecular phylogeny
      of trypanosomatids by the example of Leptomonas nabiculae podlipaev, 1987].
AB  - Results of study of Leptomonas nabiculae using various molecular markers and
      different material (cultures D2 et Nfm2) contradicted each other and taxonomic
      position of this species. We investigated morphology of the cells in these
      cultures as well as in hapantotype of L. nabiculae and those of L. peterhoffi and
      L. occidentalis that had been described from the same host species. We also
      reconstructed 18S rRNA gene phylogeny using sequences from both cultures. The D2
      culture according to its morphology and phylogenetic position revealed to be a
      Crithidia that had accompanied L. nabiculae in a mixed infection. We named it
      Crithidia dedva. The cells in the hapantotypes of the three Leptomonas species
      and those of the Nfm2 culture represent a single species that is a Herpetomonas
      (H. nabiculae) judging by morphology and molecular phylogeny. We also showed that
      the sequence of 18S rRNA gene that had been formerly determined represents a
      chimaera. This had resulted in the wrong position of this species on the
      phylogenetic tree that had contradicted results of the analysis of 5s rRNA gene.

PMID- 22384680
TI  - [The influence of the degree of infestation with trematode parthenites on the
      structure of penial glands in the mollusks Littorina saxatilis of different age].
AB  - Histological and confocal microscopy studies of the structure of penial glands in
      the Littorina saxatilis males were carried out. The examined mollusks belong to
      two age groups and were at different stages of spontaneous infection with a
      trematode from the pygmaeus species group (Microphallus piriformes). Based on
      comparative analysis of microscopic sections of copulative organs in infested and
      non-infested mollusks, data on the modifications in histological structure
      ofpenial glands were obtained. From these data we can suggest that the
      infestation have an influence on all parts of the gland. Decrease of secret
      production and reduction of muscular capsule (down to its disappearance) were
      observed. We suppose that changes in the penial glands structure prevent their
      normal functioning. In the mollusks infested on reaching the sexual maturity,
      gradual reduction of distal part of reproductive system was observed, while in
      the mollusks infested before the sexual maturity, development of ancillary part
      of reproductive system was blocked.

PMID- 22384681
TI  - [The nature of the germinal mass (gonad) in trematode parthenites (Trematoda)].
AB  - Dynamics of reproduction of the Notocotylus imbricatus (Notocotylidae),
      Echinostom caproni (Echinostomatidae), Sphaeridiotrema globulus and Psilotrema
      tuberculata (Psilostomatidae) rediae was examined. Forming of germinal mass in
      trematodes is considered and discussed on the base of literary and original data.

PMID- 22384682
TI  - [Spatial organization of musculature in the Himasthla elongata cercaria
      (Trematoda: Echinostomatidae)].
AB  - Somatic muscles (body-wall and "parenchyma" musculature), muscles of suckers,
      alimentary tract and excretory bladder of Himasthla elongata cercaria were
      investigated using fluorescent phalloidin labelling and confocal microscopy. The
      arrangement of body-wall muscles differs between the certain parts of cercarial
      body and appears to be the most complicated in the collar district. Among the
      body-wall musculature, we described U-shaped muscles, which have never been found
      previously in trematodes. Muscles of oral and ventral suckers are grouped into 6
      7 independent layers. In some of those layers, they are arranged bilaterally,
      which contradicts the tradition to consider the sucker as radially symmetric.

PMID- 22384683
TI  - [PCR identification of DNA of hosts of the taiga tick nymphs (Ixodes persulcatus:
      Ixodinae) in St. Petersburg and its suburbs].
AB  - PCR identification of host DNA in unfed females and males of taiga tick Ixodes
      persulcatus was performed. Amplification of each sample was done using primers
      species-specific by 12S rDNA mitochondrial gene. Four species of small mammals
      (Apodemus uralensis, Clethrionomys glareolus, Microtus arvalis, and Sorex
      araneus) and two passeriform bird species (Fringilla coelebs and Parus major)
      were analysed. For one third of tick samples, hosts of previous stages were
      established using this method. In five cases, feeding on more than one host
      species was detected.

PMID- 22384684
TI  - [Ways of the fleas (Siphonaptera) fauna formation in the Caucasus].
AB  - Fleas fauna of the Caucasus is considered, possible ways of its formation are
      discussed. Caucasian fleas belong to 155 species and 40 genera; 23 species are
      endemics. Hypothesis on Western Palearctic and Eastern Palearctic sources of the
      Caucasian fleas' fauna formation are proposed.

PMID- 22384685
TI  - [Evolutionary ontogenetic aspects of pathogenetics of chronic human diseases].
AB  - This article is a review of scientific publications, in which issues of
      pathogenetics of multifactorial diseases (MFDs) are considered from the viewpoint
      of evolution and ontogeny. Concepts explaining significance of evolutionary
      processes in the formation of genetic architecture of human chronic diseases
      ("thrifty" genomes and phenotypes, "drifting genes," decanalization) are
      analyzed. The roles of natural selection and genetic drift in the formation of
      hereditary diversity of genes for susceptibility to MFDs are considered. The
      modern concept of disease ontogeny (somatic mosaicism, loss ofheterozygosity,
      paradominant inheritance, epigenetic variability) is discussed. It is
      demonstrated that the evolutionary and ontogenetic approaches to analysis of
      genimuc and other "-omic" data are essential for understanding the biology of
      diseases.

PMID- 22384686
TI  - [Interacting insulators from the Drosophila melanogaster bithorax complex can
      form independent expression domains].
AB  - Regulatory region of three bithorax complex genes, Ultrabithorax (Ubx), abdominal
      A (abd-A), and Abdominal-B (Abd-B) can be divided into nine iab domains, capable
      of directing expression of one of the genes in certain abdominal parasegment of
      Drosophila. In the Abd-B regulatory region, three insulators were identified,
      including Fab-7 and Fab-8, which flanked the iab-7domain, and Mcp, which
      separated the Abd-B and abd-A regulatory regions. It was suggested that boundary
      insulators formed a barrier between active and repressed chromatin. In the
      present study, using the yellow and white reporter genes and different
      combinations of known insulators, Mcp, Fab-7, and Fab-8, it was demonstrated that
      only specific interaction of two insulators was capable of isolation of active
      and repressed chromatin, i.e., the formation of independent expression domains.

PMID- 22384687
TI  - ["Quorum sensing" regulation of lux gene expression and the structure of lux
      operon in marine bacteria Alivibrio logei].
AB  - A group of luminescent strains of marine bacteria Alivibrio logei has been
      isolated (basins of the Okhotsk, White and Bering Seas). Strains A. logei were
      shown to be psycrophiic bacteria with an optimal growth temperature of
      approximately 15 degrees C. Biolumiscent characteristics of strains were studied,
      and the expression of lux genes was shown to be regulated by the "quorum sensing"
      system. The A. logei lux operon was cloned in Escherichia coli cells and the
      structure of this operon and its nucleotide sequence were determined. The
      structure of A. logei lux operon differs markedly from that in the closely
      related species of luminescent marine bacteria A. fischeri. In the structure of
      the A. logei lux operon, the the luxI gene is absent in front of luxC, and a
      fragment containing luxR2-luxI genes is located immediately after luxG gene.
      Luminescent psycrophiic marine bacteria of A. logei are assumed to be widely
      distributed in cold waters of northern seas.

PMID- 22384688
TI  - [New allele of the COCHLEATA gene in pea Pisum sativum L].
AB  - Analysis with the polymerase chain reaction showed that the Khlorofill-4 pea
      Pisum sativum chlorophyll-deficient mutant with reduced stipules has an altered
      structure of the COCHLEATA (COCH) gene, carrying a new mutant COCH allele. The
      phenotype of the mutant was described in comparison with another form having
      reduced stipules (stipules reduced) and the control. Leaves of the coch mutant
      are smaller and have other proportions than in the control; stipules are absent
      from leaves of the first nodes and are narrow, bandlike, or spoonlike at later
      ontogenetic stages. It was concluded that the cell number in the stipule
      epidermis is reduced in the st and coch mutants compared to the wild type.

PMID- 22384689
TI  - [Molecular genetic characteristics of the Wx-B1e allele from common wheat and
      applicability of the DNA markers for its identification].
AB  - Molecular genetic characterization of the Wx-B1e allele identified by the authors
      of the study in the common wheat cultivar Korotyshka was performed. The 804-bp Wx
      B1e fragment was cloned and sequenced. Comparison of the sequence obtained with
      that for the wild-type allele of common wheat (Wx-B1a) demonstrated that Wx-B1e
      carried the 34-bp insertion, 8-bp deletion, and 23 nucleotide substitutions.
      BLAST analysis revealed the highest homology with the nucleotide sequences of Wx
      genes from Triticum spelta and Triticum durum. The amplification variants of four
      Wx-B1 molecular markers, applied worldwide for testing the collections for
      different Wx allelic variants, are demonstrated.

PMID- 22384690
TI  - Transformation of LRP gene into Brassica napus mediated by Agrobacterium
      tumefaciens to enhance lysine content in seeds.
AB  - Lysine rich protein (LRP) gene derived from the seed of Psophocarpus
      tetragonolobus was transformed into Brassica napus, employing cotyledon petiole
      as explants and by using the Agrobacterium tumefaciens strain LBA4404.
      Transformation efficiency was found to be closely related with phytohormone
      concentration, infection incubation, and co-cultured time. A medium containing 4
      mg/l 6-benzyladenine (6-BA) and 0.3 mg/l naphthalene acetic acid (NAA) was used
      for plant regeneration. With infection incubation of A. tumefaciens (OD600 = 0.4)
      for 20 min and co-culture of infected cotyledon petiole for 3 days, the highest
      transformation efficiency of 8.5% was obtained. To confirm LRP gene expression,
      PCR and Southern blot analysis were performed on leaf-isolated DNA from
      regenerated plants resistant to kanamycin. All transgenic plants of the
      generation T0 formed fertile seeds, which were sowed for the inheritance study of
      generational T1 and amino acid analysis. It was found that the lysine content of
      seeds from T1 generation increased by 16.7% compared with non-transgenic lines.

PMID- 22384691
TI  - [Microsatellite analysis of two captive populations of sable (Martes zibellina
      L.)].
AB  - The high value of sable (Martes zibellina L.) fur and stable demand for it over
      the centuries have led to suboptimal hunting patterns and, as a result,
      considerable fluctuations in the sizes of natural populations of this species. To
      maintain the traditional export of sable fur, efforts towards commercial
      domestication of sable have been made in Russia. The first farm population of
      sable consisted of animal from eight natural populations in 1929. After the
      problems related to breeding in captivity were solved, directional selection
      began. Eighty years of breeding have resulted in sable herds with homogeneous
      quantitative characters. Prospects for further breeding depend on the current
      level of genetic diversity in the captive populations of sables formed during the
      first stages of domestication. The sable populations of the Pushkinsky and
      Saltykovsky fur farms located in Moscow oblast, which were the objects of this
      study, are the progenitors of the existing captive populations. The first
      estimation of genetic variation of this species by means of a panel of
      microsatellite markers was developed for this study. Two captive sable
      populations were analyzed using ten microsatellite loci; a total of 75 alleles
      were found in both populations. Population-specific alleles were identified (6
      and 13 in the Pushkinsky and Saltykovsky populations, respectively). The
      populations studied were found to be differentiated with respect to four
      microsatellite loci.

PMID- 22384692
TI  - [Advanced approaches to studying the population diversity of marine fishes: new
      opportunities for fisheries control and management].
AB  - Recent conceptual and technological advances now enable fisheries geneticists to
      detect and monitor the dynamics and distribution of marine fish populations more
      effectively than ever before. Information on the extent of genetically-based
      divergence among populations, so-called "population diversity", is crucial in the
      quest to manage exploited living resources sustainably since it endows
      evolutionary potential in the face of environmental change. The generally limited
      dialogue between scientists, fisheries managers and policy makers, however,
      continues to constrain integration of population genetic data into tangible
      policy applications. Largely drawing on the approach and outputs from a European
      research project, FishPopTrace, we provide an example how the uncovering of
      marine fish population diversity enables players from genetics, forensics,
      management and the policy realm to generate a framework tackling key policy-led
      questions relating to illegal fishing and traceability. We focus on the use of
      single-nucleotide polymorphisms (SNPs) in European populations of cod, herring,
      hake and common sole, and explore how forensics together with a range of
      analytical approaches, and combined with improved communication of research
      results to stakeholders, can be used to secure sufficiently robust, tractable and
      targeted data for effective engagement between science and policy. The
      essentially binary nature of SNPs, together with generally elevated signals of
      population discrimination by SNPs under selection, allowed assignment of fish to
      populations from more areas and with higher certainty than previously possible,
      reaching standards suitable for use in a court of law. We argue that the use of
      such tools in enforcement and deterrence, together with the greater integration
      of population genetic principles and methods into fisheries management, provide
      tractable elements in the arsenal of tools to achieve sustainable exploitation
      and conservation of depleted marine fish stocks.

PMID- 22384693
TI  - [Population genetic structure of northern Dolly Varden char Salvelinus malma
      malma in Asia and North America].
AB  - The level of genetic differentiation of northern Dolly Varden char Salvelinus
      malma malma from Asia and North America was evaluated using the data on mtDNA
      variation (regions ND1/ND2, ND5/ND6, and Cytb/D loop) obtained by means of PCR
      RFLP analysis. For S. m. malma, the mean values of haplotype and nucleotide
      diversity were 0.5261 +/- 0.00388 and 0.001558, respectively. The mean estimate
      of the population nucleotide divergence constituted 0.055%. It was demonstrated
      that S. m. malma on the most part of the species range examined (drainages of the
      Beaufort Sea, Chukotka Sea, Bering Sea, and the Sea of Okhotsk) was characterized
      by the population genetic structure with the low level of genetic differentiation
      and divergence. At the same time, populations from the Pacific Ocean Gulf of
      Alaska demonstrated marked genetic differentiation, supported by the high
      pairwise phi(ST) values (from 0.4198 to 0.5211) and nucleotide divergence
      estimates (mean divergence, 0.129%), from Asian and North American populations.
      Nested analysis of molecular variance (AMOVA) showed that most of the mtDNA
      variation in S. m. malma fell in the intrapopulation component (72.5%). At the
      same time, the differences between the populations (21.1%) and between the
      regions (6.4%) made lower contribution to the total variation.

PMID- 22384694
TI  - [Polymorphism of immunogenetic and biochemical markers in Siberian (Tobol-Irtysh)
      Tatars].
AB  - The polymorphism of immunogenetic and biochemical markers has been studied in
      nine populations of five ethnic-geographic groups of Siberian (Tobol-Irtysh)
      Tatars. Data on the frequency distributions of 33 alleles and 6 haplotypes of 14
      loci (ABO, RHD, RHC, RHE, P, KEL, HP, C'3, TF, GLO1, ESD, ACP, PGD, and PGM1) in
      sample of 354 subjects have been obtained. Comparison with other ethnic groups
      has shown that the gene pool of Tobol-Irtysh Tatars contains an ancient
      autochthonic genetic stratum similar to that found in the neighboring Ob' Ugrian
      population. Genetic relationships of various strengths with Central Asian Turks
      and the ethnic groups of the Volga region have been found, which apparently
      reflect different stages of the ethnogenesis of the Tobol-Irtysh Tatars.

PMID- 22384695
TI  - [Cluster size polymorphism of active human ribosomal genes and simulation of the
      conditions of its stability through generations].
AB  - Based on selective silver nitrate staining of active ribosomal gene (AcRG)
      clusters in nucleolus organizer regions (NORs) of human metaphase chromosomes, a
      technique was developed earlier to estimate the AcRG dosage in individual genomes
      as a sum of arbitrary units (0-3) ascribed to the silver precipitate (AgNOR) on
      ten NORs. The AcRG dosage was considered to be an additive quantitative trait
      determined by five polymorphic autosomal loci (with for allelic forms for each
      locus). A database was created to contain the data on AcRG cluster variants for
      more than 1000 individual human genomes. In this study, the population
      frequencies of AcRG cluster variants were determined. The results agreed with the
      hypothesis that stabilizing selection acts at the zygotic and/or early
      embryogenetic stage to restrain the AcRG genomic dosage (copy number) within a
      range from 14.9 to 23.7 arbitrary units (the cell is unviable when the trait is
      beyond this range). The average zygotic losses due to selection were estimated at
      9.1-9.9% for a real population. A computer model where the AcRG dosage of a
      progeny results from a random combination of the AgNORs of the five acrocentric
      chromosome pairs of the parents was developed and used to simulate the formation
      of a certain AcRG genomic dosage through generations in a human panmictic
      population with nonoverlapping generations. A combination of stabilizing
      selection by total AcRG copy number and a certain spontaneous mutation rate (the
      probability of changes in the cluster size of a NOR as a result of unequal
      crossingover in meiotic prophase) was shown to be a sufficient condition for the
      restrain of equilibrium population frequencies of AgNOR size variants in a human
      panmictic population. Using the model, the most probable spontaneous mutation
      frequency was predicted to be (2.1-2.3) x 10(-2) per NOR per generation for human
      AgNORs. The predicted frequency was within the 95% confidence interval of the
      experimental rate, which was determined by studying the inheritance of AgNOR
      variants in real families.

PMID- 22384696
TI  - [Evolutionary trends in the prokaryotic community and prokaryotic community-phage
      systems].
AB  - The Evolutionary Constructor software has been used for computer simulation of
      the life and evolution of communities of unicellular haploid organisms
      (prokaryotic cells). Opposite trends of the community evolution (simplification
      and complication of the genome) have been studied. It has been demonstrated that
      species with reduced genomes tend to replace genetically and metabolically rich
      species under highly favorable environmental conditions. Under unfavorable
      conditions, the opposite tendency is observed. It has also been shown that
      introduction of phages capable of killing the cells into the system may radically
      change the current evolutionary trend.

PMID- 22384697
TI  - [CYP2E1 gene polymorphism and ovarian cancer risk in the Yakut population].
AB  - The CYP2E1 gene polymorphism has been studied in Yakut women with ovarian cancer
      and without cancer. The two groups have been found to substantially differ in the
      frequency of the CYP2E1* 1D allele (with a 96-bp insertion in the promoter region
      of the gene): it is more frequent in healthy women (16.3 versus 7.4%, P = 0.007).

PMID- 22384699
TI  - [Mechanism of a splenic injury development in the case of the one-step course of
      the traumatic process].
AB  - Taken together, the results of analysis of the major types of deformation of
      elastic objects (compression, stretching, shear) and of combined injuries to the
      spleen and its ligamentous apparatus were used to construct a table for
      differential diagnostics of the mechanisms governing the factors responsible for
      different types of the injury. Special emphasis is laid on the site of injurious
      action and its direction with respect to the one-step development of the
      traumatic process.

PMID- 22384698
TI  - [Characteristics of stab wounds inflicted by knives with the gear-sharpened
      blade].
AB  - The authors present the results of an experimental study designed to estimate the
      damage to biological and non-biological objects inflicted by the knife blades
      having the gear-type sharpening. It was shown that a knife with such sharpening
      leaves edges of the damage of characteristic shape and outline. The results of
      the study testify to the expediency of further studies on the damaging action of
      knives considered in the present paper.

PMID- 22384700
TI  - [Characteristics of the injuries to diaphyses of the long tubular bones in case
      of skew bending].
AB  - The present experimental study was designed to elucidate specific morphological
      features emerging from the destruction of diaphyses of long tubular bones
      undergoing a combined strain/stress impact. It is concluded that the species
      specific signs of the injuries to the long tubular bones can be used for the
      purpose of their differential diagnosis from other types of injuries.

PMID- 22384701
TI  - [The application of the immunohistological method for the detection of ABO
      antigens in cellular elements].
AB  - This paper was designed to illustrate the advantages of immunohistological
      methods over those traditionally employed in this country for the study of
      material evidence. A method for the identification of ABO antigens in cellular
      elements based on the use of Diagnostic BioSystems-Universal HPP kits is
      described. The reaction is specific and as sensitive as the immunofluorescent
      techniques. The stained preparations can be stored during a long period without
      the loss of their properties. The authors recommend to use the method being
      considered in forensic medical (specifically, in forensic cytological) practice.

PMID- 22384702
TI  - [A new algorithm for the establishment of blood relationship based on the
      application of the dermatoglyphic technique].
AB  - An original classification of dermatoglyphic features is proposed taking into
      consideration their inter-relations in conjunction with the new principles of
      comparative studies. A new and improved algorithm for the establishment of blood
      relationship has been developed based on the application of the dermatoglyphic
      technique. The method is recommended for the use in forensic medical expertise
      for the purpose of estimation of the probability of paternity, maternity, and
      substitution of children. Moreover, it may find application for the indirect (via
      establishment of blood relationship) identification of personality of an unknown
      subject.

PMID- 22384703
TI  - [Lethal poisoning with the death-cap mushrooms].
AB  - We have analysed morphological manifestations in five cases of lethal poisoning
      with the Death Cap toxin and compared the relevant clinical and laboratory
      findings with those in 15 survived subjects. It was shown based on the results of
      autopsy that poisoning was associated with hepatopathy, extensive hepatic
      necrosis, and nephropathy. Elevated blood bilirubin levels in conjunction with
      lowered prothrombin and fibrin concentrations appear to be the main causative
      factors responsible for the unfavourable prognosis of this intoxication.

PMID- 22384704
TI  - [Tissue distribution of tetramethylthiuram disulfide in warm-blooded animals].
AB  - The objective of the present work was to study the distribution of
      tetramethylthiuram disulfide (TMTD) in the body of warm-blooded animals as
      exemplified by white rats. TMTD was administered intragastrically and detected in
      the unaltered form in other internal organs. It was found to accumulate in the
      largest amounts in the gastric contents, kidneys, and urine.

PMID- 22384705
TI  - [The influence of an air ionizer on the air ionic composition].
AB  - The air ionic composition in a classroom was determined during the operation of a
      Neo Tec XJ-2100 ionizer (Germany). The amount of ions in the air was measured
      before and after the switch-on of the ionizer. It was shown to vary depending on
      the mode of operation of the device and differ from the recommended normal
      values. The necessity of checking up the work of air ionizers both in living
      quarters and at workplaces is discussed with the application of air ion counters
      making it possible to carry out monitoring of the air ionic composition and
      estimate its compliance with the sanitary and hygienic norms.

PMID- 22384706
TI  - [The data on statistical surveillance of recording forensic medical expertises of
      the harm to human health collected by the Bureau of Forensic Medical Expertise
      (BFME) in Central Health Department of the Moscow region].
AB  - This publication deals with the analysis of application of the "Medical criteria
      for the harm to human health" put into force on September 16, 2008, as
      exemplified by the work of the Bureau of forensic medical expertise (BFME),
      Central Health Department of the Moscow region, during the period from 2007 and
      2010. The data were borrowed from the materials of departmental statistical
      reporting (F.42) on forensic medical examinations of the harm to human health
      carried out during the period between 2007 and 2010. In addition, the statistical
      report of BFME on the application of the medical criteria in 2010 was used. The
      number of forensic medical expertises for the estimation of the degree of harm to
      human health was shown to decrease by 9% but remain 3% higher than the average
      across the country. The number of expertises of severe harm to the health
      increased by 15% as in the whole of the country with the concomitant 20%
      reduction in the number expertises of mild and moderate harm. These trends are
      unrelated ether to the changes in the frequency of crimes leading to the serious
      harm to the health or to the number of subjects convicted of such crimes. It was
      found that p.p. 6.1.1 - 6.1.30 of the "Medical criteria" that list life
      threatening injuries are most frequently (in 58% of the cases) used to document
      facts of severe harm to the health. The same is true of p.p. 6.11. - 6.11.11
      listing the injuries responsible for the persistent loss of occupational capacity
      (by at least one third). The frequency of application of concrete paragraphs of
      the (Medical criteria, is determined within each group. The largest number of
      expert errors (3.2%) were committed while estimating serious harm to the health
      based on the paragraphs listing the injuries responsible for the persistent loss
      of occupational capacity (by at least one third). The minimal number of such
      errors (1%) were committed while estimating serious harm to the health from life
      threatening injuries.

PMID- 22384707
TI  - [The methodological basis of expert assessment of unfavourable outcomes of the
      stomatological treatment in the framework of civil law proceedings].
AB  - The authors discuss peculiarities of the performance of forensic medical
      expertise in the cases of unfavourable outcomes of the stomatological treatment.
      The methodological basis of expert assessment has been created to be applied in
      situations related to the unfavourable outcomes of dental care.

PMID- 22384708
TI  - [Marks on the human and animal skin after contact with an electrical discharge
      device].
AB  - Skin injuries in a subject affected by the current generated in an electrical
      discharge device are described. The macroscopic and microscopic picture of the
      injuries inflicted with the use of a similar device in experimental animals is
      presented.

PMID- 22384709
TI  - [The use of modern high-intensity radiation sources for the discovery and
      identification of the traces in the biological and molecular-genetic expertise].

PMID- 22384710
TI  - [On the state of the budgetary funding of government forensic medical expert
      institutions in the Russian Federation].
AB  - The data on the budgetary funding of state-owned forensic medical bureaus in the
      Russian Federation for the period from 2005 to 2008 were collected and analysed.
      The results of the overall estimation and parameters characterizing the level of
      funding of these expert facilities are presented. Selected state forensic medical
      bureaus have been ranked based on the level of their financial support.

PMID- 22384711
TI  - [The modern concepts of placental pathology and its role in perinatal mortality
      in the context of forensic medical practice].
AB  - The modern concepts of placental pathology are considered and analysed in the
      context of forensic medical practice. The most promising approaches to the
      application of fundamental knowledge of placental pathology (including
      morphometric methods) for the purpose of forensic medical expertise are
      discussed.

PMID- 22384712
TI  - [Professor Ivan Fedorovich Vensovich--an enigma of forensic medicine].

PMID- 22384713
TI  - [Adaptive response of blood lymphocytes as a marker of hemopoiesis status in
      exposed persons].
AB  - An obvious correlation between the type of reaction manifested by peripheral
      blood lymphocytes to low dose irradiation in vitro (adaptive potential), the RBM
      cell composition (during the period of the major exposure), and the peripheral
      blood cell composition (at a late time period coincident with the studies of
      induced radioresistance) has been found in the Techa riverside residents in the
      later periods after the onset of a long-term low-dose rate radiation exposure (55
      60 years later) within a range of individual red bone marrow doses from 0.01 to
      1.79 Gy. The nature of these dependences observed in chronically exposed
      individuals differs from that revealed in the controls. It can be suggested based
      on the results of the study that the capacity for the adaptive response shown by
      peripheral blood lymphocytes donated by exposed persons in the remote period
      after exposure can be regarded as a biological marker of the functional state of
      the hemopoietic stem cell pool.

PMID- 22384714
TI  - [DNA-signaling pathway mediating development of a radiation-induced bystander
      effect in human cells].
AB  - Low doses of ionizing radiation induce the adaptive effect (AE) development in
      human cells which is followed by a number of cell responses. These responses can
      be transmitted from irradiated cells to non-irradiated ones (bystander effect,
      BE). The major role in radiation-induced BE is played by an oxidative stress (OS)
      and a DNA-signaling pathway, in which extracellular DNA fragments (ecDNA) are the
      factors of stress-signalization. We propose the following sequence of events in
      this signaling system: irradiation-OS-DNA modification-apoptosis of irradiated
      cells-ecDNA-signal acceptance by non-irradiated cells-OS-DNA modification, etc.
      We observed a radiation-induced BE which is accompanied by DNA-signaling pathway
      in differentiated and undifferentiated human cells forming monolayer or
      suspension cultures. Here we discuss several aspects of the radiation-induced BE
      mechanism and its persistence possibilities.

PMID- 22384715
TI  - [Oxazole derivatives as compounds modifying radiation effects in the body of
      mice].
AB  - A new class of substances exhibiting radioprotective and radiosensitizing effects
      depending on the concentration of the substance has been found. The
      radioprotective effect is probably due to the resonant absorption of radiation
      energy and its transformation into low-energy forms, as well as reactions with
      water radiolysis products. We studied the effects of 2,5-difeniloxazole and di[2
      (5-feniloxazolil)]benzene in various concentrations in conjunction with
      irradiation on the growth of melanoma B-16 in mice and the average time of their
      lives. When using individual doses of irradiation and doses of preparations, we
      observed an increase in the average lifetime of mice and a reduced tumor size.
      These data allow us to conclude about the possibility of using these substances
      in the radiotherapy of tumors.

PMID- 22384716
TI  - [Immediate and delayed effects of low doses of beta-radiation in mammalian cells
      in culture].
AB  - We have carried out the comparative examination into the efficacy of induction of
      NO and superoxide anion by incorporated and unincorporated sources of ionizing
      radiation in endotheliocytes (line ECV 304) and carcinoma cells (line HeLa G63)
      expressing various forms of NO-synthases. The increased intracellular nitric
      oxide levels were observed after exposure of the cells to beta-particles of 3H
      thymidine and 3H2O, as well as to gamma-rays of 137Cs in HeLa G63 cells
      expressing the inducible forms of NO-synthases. A higher incidence of the
      intracellular NO level was observed after exposure to beta-particles of 3H2O than
      to beta-particles of 3H-thymidine or gamma-rays of 137Cs even though 3H-thymidine
      and gamma-rays elicited more chromosomal damages. Modification of the
      intracellular superoxide level was shown to have a similar dynamics of the
      changes in time for the both cellular lines. Shortly after irradiation, the
      intracellular superoxide level was lower than in non-irradiated cells, and then
      it became higher than the control level. The increased intracellular superoxide
      and NO levels were observed after exposure of the cells to beta-particles of 3H
      thymidine and 3H2O, as well as to gamma-rays of 137Cs in the progeny of
      irradiated cells. Modification of the intracellular superoxide level was
      accompanied by decondensation of the cellular chromatin. A higher intracellular
      free radical level in the progeny of irradiated cells along with decondensation
      of cellular chromatin, as well as the absence of correlation between a radiation
      induced structural damage of chromosomes and intracellular free radical level
      allow us to speculate in favor of the participation of epigenetic inheritance
      mechanisms.

PMID- 22384717
TI  - [X-ray irradiation stimulates the mitochondrial-dependent generation of reactive
      oxygen and nitrogen species in K562 leukemia cells].
AB  - The dynamics of radiation-induced oxidative and nitrative stress, the source of
      oxygen and nitrogen reactive species in cancer cell line K562 and the role of
      mitochondria in these processes have been studied. The study was performed using
      K562 leukemia cell cultures. Intracellular concentration of reactive oxygen
      species (ROS), nitrogen oxide, and the mitochondrial potential were analyzed
      after 15, 30 min, 1, 4, 8, 12, 24, and 48 h after irradiation by X-rays at a dose
      of 4 and 12 Gy. Radiation-induced generation of ROS in K562 cells has two time
      peaks, the first peak was recorded after 30 min and the second 24 h after
      exposure to X-rays. Mitochondria are responsible for the increase of the ROS
      concentration in the period of 12-48 h after irradiation. The increase in ROS
      concentrations is accompanied by the increase of the mitochondrial potential. The
      intracellular concentration of nitric oxide begins to grow 8 h after exposure.
      The increase in the mitochondria-dependent ROS production is accompanied by the
      increase in the intracellular concentration of nitric oxide.

PMID- 22384718
TI  - [Functioning of the antioxidant system in epithelial cells of small intestine
      under the influence of ionizing radiation of low dose rate].
AB  - The investigations of the functional state of the antioxidant system in
      epithelial cells from rat small intestine in dynamics after X-ray irradiation
      (0.1; 0.5 and 1.0 Gy) at a low absorbed dose rate (55 mGy/min) were performed.
      The obtained results point out the ambiguity of the antioxidant system reaction
      to the activation of oxidative processes at different doses of irradiation. The
      multidirectional changes of these antioxidant enzymatic activities whose
      functioning is characterized by the early post-irradiation recovery depending on
      the value of the absorbed dose were observed. The sensitivity of superoxide
      dismutase, glutathione transferase and glutathione peroxidase in mitochondria of
      epithelial cells to the irradiation exposure in the investigated range of
      absorbed doses was shown.

PMID- 22384719
TI  - [Lipids of neocortex after X-ray irradiation of the rat head at a dose of 200
      Gy].
AB  - X-ray irradiation at a dose of 200 Gy with local exposure of the rat head induced
      the change of the lipid content in the neocortex tissue. The amount of
      phosphatidylinositol was decreased, the amount of free fatty acids, diglycerols,
      sphingomyelin was increased, and the amount of cholesterol had a growth trend in
      2 h after X-ray exposition. The results testify in favor of participation of
      phosphatidylinositol- and sphingomyelin-relating signal systems and cholesterol
      in early stages of the cerebral radiation syndrome. We suggest that the change of
      the lipid content in early periods after the effect of a super-high dose of X-ray
      irradiation indicates the lipid dependence in the elimination of motion damages
      and the restoration of the functions of nerve cells. Effects on the lipid
      metabolism in the nerve tissue are promising for correcting the cerebral
      radiation syndrome.

PMID- 22384720
TI  - [Experimental study of the effect of detoxification with enterosorbents on the
      function of irradiated myocardium].
AB  - Increase in intoxication products, such as medium size peptides, indole and
      myoglobin, in urine was observed in Wistar rats after exposure of their chest to
      gamma-radiation at a dose of 6 Gy (dose rate 4 Gy/min). The rats exhibited
      moderate ischemic ECG. Administration of enterosorbents, such as Smekta and Clay
      of Kaluga deposit, to the irradiated rats resulted in the decrease of the
      toxicant content in the animals and the recovery of the cardiac function on the
      28th day. These sorbents had practically a similar efficacy.

PMID- 22384721
TI  - [Evaluation of effects of gamma-irradiation at low doses on repair and meiotic
      recombination mutants of Drosophila melanogaster].
AB  - A comparative study of the effects of gene mutations mus209, mus309, mei-41 and
      rad54 of Drosophila melanogaster on the sensitivity to low-level exposure of
      different duration was carried out. Taken into account was the survival rate at
      different stages of ontogeny, female fecundity, the frequency of dominant lethal
      mutations (DLM) and the DNA damage. mei-41 and rad-54 mutants were most sensitive
      to the action of low dose radiation (80 mGy) in terms of survival and DLM.
      However, at the level of DNA damage, an increased radiosensitivity is observed
      only at larger doses of low intensity irradiation. Based on these observations,
      we can conclude about the importance of repair and its genes in the formation of
      the effect of low level doses of ionizing radiation in Drosophila.

PMID- 22384722
TI  - [Case-control study of lung cancer and combined home and work radon exposure in
      the town of Lermontov].
AB  - Relation between the risk of lung cancer and combined home and work indoor radon
      exposure was studied on the example of the population of Lermontov town
      (Stavropol Region, Russia). The town is situated in the former uranium mining
      area. Case (121 lung cancer cases) and control (196 individuals free of lung
      cancer diagnosis) groups of the study included both ex-miners and individuals
      that were not involved in the uranium industry. Home and work radon exposures
      were estimated using archive data as well as contemporary indoor measurements.
      The results of our study support the conclusion about the effect of radon
      exposure on the lung cancer morbidity.

PMID- 22384723
TI  - [Application of laser interference microscopy (LIM) for investigating the
      features of UV(B)-irradiated mouse peritoneal macrophages].
AB  - The plasma membrane dose-dependent damage of UV(B)-irradiated mouse peritoneal
      macrophages was investigated using laser interference microscopy (LIM). LIM is a
      method which allows one to estimate morphological and functional parameters of a
      cell without dyeing or introduction of other substances which can affect the cell
      condition. This makes it possible to reduce and accelerate the procedure of
      counting the damaged cells as compared with the methods using different dyes. The
      value of optical path difference (OPD)--a variable proportional to the object
      thickness and the difference in the refractive indices of the object and the
      surrounding medium was used for estimation of the cell damage. Also compared was
      usability of LIM and microfluorimetry assay in investigations of the UV(B)
      irradiated macrophage plasma membrane.

PMID- 22384724
TI  - [New data for proving the presence of significant effects of electromagnetic
      exposure (to autoimmune changes in rats)].
AB  - The study using statistical analysis methods and the generalized logarithmic
      parameter describing the change in the condition of biological systems represents
      additional substantiations and proofs of the presence of the expressed
      amplification of the immune reaction in experimental animals after a long
      exposure to EMF RF non-thermal intensity with a power density of 500 microW/cm2.
      A substantial growth of titers of antibodies to the brain tissue on the 14th day
      and to a number of other antigens on the 7th and 14th days after irradiation is
      shown with high reliability of 99.9%. It is shown that EMF RF exposure to non
      thermal intensity within 30 day causes transition of an organism to an active
      adaptation described by an amplified strengthening of intensity of the regulation
      systems of the organism.

PMID- 22384725
TI  - [Application of the ferrocin containing waste of wine-making for reduction of
      137Cs tansit from forage to laboratory animal organisms and cow milk].
AB  - Addition to rat ration of ferrocin containing wastes of wine-making formed during
      the process of wine demetalization in the amount of 0.2 g per animal per day
      reduces the 137Cs content in organs and tissues in 1.5-7 times. Addition of the
      above-mentioned substance to the ration of milk cows in the amount of 10-16 g per
      day reduces the radionuclide content in milk 1.5-2 times in two weeks and more
      than 3 times in four weeks.

PMID- 22384726
TI  - [Melatonin as a universal stabilizing factor of mental activity].
AB  - Pineal hormone melatonin stabilizes mental activity of man and animals due to its
      somnogenic, anxiolytic, antidepressant and nootropic properties. Melatonin
      effects are based on the synchronization of biological rhythms via the influence
      on the cerebral structures which control biological rhythms and emotions and
      normalize endocrine and immune state.

PMID- 22384727
TI  - [Neural mechanisms of memory: synaptic and genomic hypotheses].
AB  - Memorizing of new facts and events means that entering signals produce definite
      changes within the brain. According to the commonly accepted hypothesis, traces
      of memory are stored through modifications in the strength of synaptic
      connections, resulting in formations of new patterns of neural activity. This
      synaptic hypothesis of memory determines the main direction of experimental
      studies in the field. It is shown in this review that the synaptic hypothesis can
      hardly explain the mechanism of long-term (often life-long) memory storage as
      well as memory resistance to both uncontrolled synaptic activity (epileptic
      seizures) and various adverse effects on the brain (anesthesia, injury,
      concussion, etc.). Arguments for an alternative hypothesis are given that long
      term memory is mainly formed at the intraneural level through modifications of
      DNA molecules and associated proteins. This genomic hypothesis allows for a new
      approach to understanding the etiology ofAlzheimer's disease, whose initial
      symptom is solely memory impairment.

PMID- 22384729
TI  - [Neurophysiological model of cognitive space].
AB  - The aim of the study was to find out how EEG rhythmical patterns change with
      gradual changes of a degree of verbal and spatial thinking involved in the
      process of task solving. The obtained data allowed us to draw two principally new
      conclusions. 1. During performance of mixed tasks the spatial and verbal thinking
      do not mix, and their rhythmical signs are both present with their basic
      properties preserved. A mixed rhythmical pattern is thus a superposition of a
      spatial and a verbal pattern. 2. It is possible to introduce a "distance" between
      mental conditions as a measure of difference in the corresponding EEG power
      spectra. With such distances calculated, multidimensional scaling methods may be
      used to represent cognitive states as points on a plane. Cognitive states form
      constellations with shapes reasonably reflecting psychological properties of
      cognitive tasks. The results suggest the existence of a "cognitive space", whose
      structure may be revealed by objective electrophysiological methods.

PMID- 22384728
TI  - [Induced cortical electrical activity during different time-spans between warning
      and target stimuli].
AB  - A certain alpha-band EEG dynamics was revealed in healthy adults (n = 16) at the
      interval between a warning and a target stimulus in a simple visuospatial task
      (subjects were instructed to locate a specific letter in the table of letters).
      Two series of experiment--either with a 2-sec or a 9-sec inter-stimulus interval
      were conducted, each consisting of 60 trials. In both series, we observed an
      induced desynchronization of low alpha (8-10 Hz) at the first second after the
      warning stimulus and its desynchronization just before the target stimulus. In
      series with a 9-sec inter-stimulus interval at the 4-6 s of it we observed an
      alpha-band synchronization, especially distinct in high alpha (10.5-13 Hz). This
      synchronization gradually reduced towards the end of the inter-stimulus interval.
      We consider the above changes in alpha-band spectral power during the inter
      stimulus interval to be induced by "inner impulsations" caused by an internal
      representation (set) of the stimuli time-sequence. Changes in the level of
      cognitive control during the inter-stimulus interval cause increases and
      decreases in fronto-thalamic system activity, which are manifested in changes of
      alpha-band spectral power. Analysis of theta-band dynamics suggests that cortico
      hippocampal system doesn't participate in this process.

PMID- 22384730
TI  - [Features of perception of length of segments under conditions of ponzo and
      Muller-Lyer illusions in schizophrenia].
AB  - In order to better appreciate the neurophysiologic mechanisms of perception of
      length under conditions of geometrical visual illusions, we studied sensitivity
      of mentally healthy subjects and schizophrenic patients to Ponzo and Muller-Lyer
      illusion. Patients with schizophrenia estimated length of segments of Muller-Lyer
      figure less precisely. Accuracy of perception of length of segments in Ponzo
      figure was ambiguously connected with the duration of the disease. Persons
      suffering from schizophrenia for a short time were less inclined to Ponzo
      illusion than mentally healthy subjects. On the contrary, patients who suffered
      from schizophrenia for a long time were more sensitive to this illusion. Ponzo
      illusion can be used as a marker of schizophrenia which is found out during the
      specific period of development of the disease. High sensitivity of patients with
      schizophrenia to Muller-Lyer and Ponzo illusions supports a hypothesis about the
      role of the global analysis of an image during processing of its low-frequency
      component in formation of the illusions under study.

PMID- 22384731
TI  - [Topographic characteristics of cortex activity in delta-, alpha2-, and gamma2-
      frequency bands related to social creativity].
AB  - Social creativity-related topographic changes of the delta, alpha2, and gamma2
      power were studied using 19-channel EEG. Originality and fluency indices of
      social thinking were evaluated on basis of specially developed 'divergent' task
      solution that stimulated different interpretations of social scenes; complex
      visual stimuli (architectural building) were used as control task. 'Divergent'
      task performing was characterized by both the greater power of the delta and
      alpha2 rhythms mostly in the right hemisphere and widespread increase in the
      gamma2 power as compared with the control task. Positive correlations between
      delta and gamma2 rhythms in baseline condition were revealed in the fronto
      parietal cortex, and this relationship between low- and high-frequency
      oscillations while 'divergent' task performing was found in the right posterior
      cortex. Special topographic patterns of delta and gamma2 activity as predictors
      of social creativity were obtained using multiple regression analysis. These
      patterns can be interpreted as EEG correlates of a summation of endogenous and
      exogenous components of social thinking.

PMID- 22384732
TI  - [EEG correlates of aggression and anxiety in a social interaction model].
AB  - Aggressiveness- and anxiety-related behavioral and oscillatory patterns were
      investigated in 49 18-30 year old subjects during virtual social interactions.
      The subjects were presented with pictures of "angry", "happy", and "neutral"
      faces and had to choose one out of three options: "attack", "avoid", or "make
      friends". Sources of cortical EEG were localized with sLORETA software. Subjects
      with high aggressiveness chose attack more frequently and this behavior was
      accompanied by a stronger induced delta and theta synchronization in the right
      orbitofrontal cortex. In subjects with high anxiety, delta and theta responses
      were stronger induced in the right temporal cortex during their more frequent
      avoidance behavior. Thus, both in anxious and in aggressive subjects, typical
      behavior was accompanied by increased induced low-frequency synchronization whose
      localization implies that it is associated with motivational and emotional
      processes.

PMID- 22384733
TI  - Network effects of glutamate on neuronal activity in the medial septum/diagonal
      band complex in vitro.
AB  - Inter-neuronal interactions within the medial septum/diagonal band complex (MSDB)
      are of great interest as this region is believed to be the hippocampal theta
      rhythm pacemaker. However, the role of glutamatergic system in functioning of the
      septal cells is yet unclear. Here, we demonstrate for the first time the effects
      of glutamate in physiological concentration (1 microM) on the MSDB neuronal
      spontaneous and evoked activities in vitro. These effects (activation of 70% and
      inhibition of 30% of responsive neurons) differed in pacemaker and non-pacemaker
      cells. Pacemaker cells were always activated under glutamate, whereas non
      pacemaker neurons could be either activated or inhibited. Indeed, in the burst
      pacemakers, glutamate increased the frequency of rhythmic activity. In a total
      MSDB neuron population, in 30% of neurons glutamate applications modified
      responses to the electrical stimulation by unifying the temporal parameters of
      neuron responses. Along with the increase in the theta-burst frequency, this
      indicates that the glutamatergic system is involved in the process ofintraseptal
      synchronization. Obtained data shed light on the role ofglutamatergic system in
      septal neuron interactions and broaden our understanding of theta oscillation
      mechanisms in the septo-hippocampal system.

PMID- 22384734
TI  - [Impairments of conditioned behavior in adult rats induced by interleukine-1beta
      treatment in early postnatal ontogenesis].
AB  - Impairments of cognitive functions in children and adolescents are often
      consequences ofperinatal pathology (natal injuries, ischemia, hypoxia, infection
      and allergic diseases), which are accompanied by enhanced production
      ofproinflammatory cytokine interleukine-1beta. In this work it was shown that
      treatment with interleukine-1beta during the third week of life impaired active
      and passive avoidance conditioning in adult rats at the age of 60-70 days.

PMID- 22384735
TI  - [Selection of mice for high level of extrapolation capacity with cobcommitant low
      anxiety level].
AB  - The behavior scores were assessed in mice selected simultaneously for high
      percentage of correct extrapolation task solutions and for low anxiety during
      test performance. Extrapolation test requires that the hungry animal searches for
      the food bait which disappeared from the view moving in the direction of food
      bait movement. In the 4th selection generation no significant changes occurred in
      the percentage of correct task solutions neither in comparison to control
      unselected population, nor against 50% chance level. Although the proportion of
      mice in selected strain which performed with 80-100% of correct solutions
      increased and in F4 was higher in comparison to controls (approaching
      significance). The proportion of "0" solution (when mouse made no choice) and of
      "refusals" of performance (anxiety indices in this test) were lower in selected
      line and the proportion of refusals in F4 was significantly lower than in
      controls. Elevated plus maze, closed plus maze and inescapable slippery funnel
      tests demonstrated significantly lower anxiety in mice of selected strain. These
      data demonstrate much more complex genetic basis for the capacity for
      extrapolation (lack of response to selection) in comparison with that of anxiety
      traits in mice (changes in the response to selection).

PMID- 22384736
TI  - [Functional organization and structure of the serotonergic neuronal network of
      terrestrial snail].
AB  - The extension of knowledge how the brain works requires permanent improvement of
      methods of recording of neuronal activity and increase in the number of neurons
      recorded simultaneously to better understand the collective work of neuronal
      networks and assemblies. Conventional methods allow simultaneous intracellular
      recording up to 2-5 neurons and their membrane potentials, currents or
      monosynaptic connections or observation of spiking of neuronal groups with
      subsequent discrimination of individual spikes with loss of details of the
      dynamics of membrane potential. We recorded activity of a compact group of
      serotonergic neurons (up to 56 simultaneously) in the ganglion of a terrestrial
      mollusk using the method of optical recording of membrane potential that allowed
      to record individual action potentials in details with action potential
      parameters and to reveal morphology of the neurons rcorded. We demonstrated clear
      clustering in the group in relation with the dynamics of action potentials and
      phasic or tonic components in the neuronal responses to external
      electrophysiological and tactile stimuli. Also, we showed that identified neuron
      Pd2 could induce activation of a significant number of neurons in the group
      whereas neuron Pd4 did not induce any activation. However, its activation is
      delayed with regard to activation of the reacting group of neurons. Our data
      strongly support the concept of possible delegation of the integrative function
      by the network to a single neuron.

PMID- 22384737
TI  - [Coherence and phase analysis of theta-oscillations in the septohippocampal
      system during seizures].
AB  - Interrelations of the hippocampus and medial septal area (MSA) in the theta band
      (4-8 Hz) were studied during seizures produced by electrical kindling in waking
      guinea pigs. Field activity (EEG) was analyzed using the wavelet transform. A
      decrease in coherence of theta-oscillations in the hippocampus and MSA was
      observed during seizures. Phase analysis showed that in the beginning of kindling
      the MSA led in phase, but after formation of the pathological focus, MSA lagged
      the hippocampus. The data may contribute to understanding mechanisms of temporal
      lobe epilepsy.

PMID- 22384738
TI  - Building connections on the care continuum.

PMID- 22384739
TI  - Mobile health is in the regulatory crosshairs.

PMID- 22384740
TI  - User unfriendly.

PMID- 22384741
TI  - Scrambling I.T. to address drug shortages.

PMID- 22384743
TI  - Putting social networks on trial.

PMID- 22384742
TI  - Nurses rounding up I.T. to improve safety.

PMID- 22384744
TI  - Information governance: the essential accountability wrapper.

PMID- 22384745
TI  - EHR game changer makes I.T. fit the clinician.

PMID- 22384746
TI  - Safety engineer. Interview by Elizabeth Gardner.

PMID- 22384747
TI  - Regarding the confusion between the population concept and Mayr's "population
      thinking".
AB  - Ernst Mayr said that one of Darwin's greatest contributions was to show scholars
      the way to population thinking, and to help them discard a mindset of typological
      thinking. Population thinking rejects a focus on a central representative type,
      and emphasizes the variation among individuals. However, Mayr's choice of terms
      has led to confusion, particularly among biologists who study natural
      populations. Both population thinking and the concept of a biological population
      were inspired by Darwin, and from Darwin the chain for both concepts runs through
      Francis Galton who introduced the statistical usage of "population" that appears
      in Mayr's population thinking. It was Galton's "population" that was modified by
      geneticists and biometricians in the early 20th century to refer to an
      interbreeding and evolving community of organisms. Under this meaning, a
      population is a biological entity and so paradoxically population thinking, which
      emphasizes variation at the expense of dwelling on entities, is usually not about
      populations. Mayr did not address the potential for misunderstanding but for him
      the important part of the population concept was that the organisms within a
      population were variable, and so he probably thought there should not be
      confusion between population thinking and the concept of a population.

PMID- 22384748
TI  - Central nervous system and computation.
AB  - Computational systems are useful in neuroscience in many ways. For instance, they
      may be used to construct maps of brain structure and activation, or to describe
      brain processes mathematically. Furthermore, they inspired a powerful theory of
      brain function, in which the brain is viewed as a system characterized by
      intrinsic computational activities or as a "computational information processor.
      "Although many neuroscientists believe that neural systems really perform
      computations, some are more cautious about computationalism or reject it. Thus,
      does the brain really compute? Answering this question requires getting clear on
      a definition of computation that is able to draw a line between physical systems
      that compute and systems that do not, so that we can discern on which side of the
      line the brain (or parts of it) could fall. In order to shed some light on the
      role of computational processes in brain function, available neurobiological data
      will be summarized from the standpoint of a recently proposed taxonomy of notions
      of computation, with the aim of identifying which brain processes can be
      considered computational. The emerging picture shows the brain as a very peculiar
      system, in which genuine computational features act in concert with
      noncomputational dynamical processes, leading to continuous self-organization and
      remodeling under the action of external stimuli from the environment and from the
      rest of the organism.

PMID- 22384749
TI  - Multiple sclerosis is not a disease of the immune system.
AB  - Multiple sclerosis is a complex neurodegenerative disease, thought to arise
      through autoimmunity against antigens of the central nervous system. The
      autoimmunity hypothesis fails to explain why genetic and environmental risk
      factors linked to the disease in one population tend to be unimportant in other
      populations. Despite great advances in documenting the cell and molecular
      mechanisms underlying MS pathophysiology, the autoimmunity framework has also
      been unable to develop a comprehensive explanation of the etiology of the
      disease. I propose a new framework for understanding MS as a dysfunction of the
      metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses
      during acute-phase inflammatory response triggered by a pathogen, trauma, or
      stress, starting a feedback loop of increased oxidative stress, inflammatory
      response, and proliferation of cytoxic foam cells that cross the blood brain
      barrier and both catabolize myelin and prevent remyelination. Understanding MS as
      a chronic metabolic disorder illuminates four aspects of disease onset and
      progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental
      and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests
      new avenues for treatment.

PMID- 22384750
TI  - Prescribing opioids safely in patients with an opiate allergy.

PMID- 22384751
TI  - What is behind this postpartum puzzler? PUPP.

PMID- 22384752
TI  - HIV/AIDS: improved outcomes, less disparity.

PMID- 22384753
TI  - Battling influenza: universal vaccination is the primary weapon.

PMID- 22384754
TI  - Clostridium difficile: a new look at an old but increasingly deadly infection.

PMID- 22384755
TI  - An internal hernia causes abdominal pain and small bowel obstruction.

PMID- 22384756
TI  - C-reactive protein: a clinically useful biomarker in renal cell carcinoma.

PMID- 22384757
TI  - The characteristics of clinically active older physician assistants.
AB  - OBJECTIVE: To prepare for future health workforce requirements, planners need an
      understanding of the clinical activity of physician assistants (PAs) and their
      career trajectory. We compared the characteristics of clinically active older PAs
      to younger PAs. METHOD: PAs were identified from all respondents aged 60 years or
      older at the time they participated in the annual census of the AAPA from 2005
      through 2009. The most recent year of census participation was selected for
      analysis. This cadre of older PAs was compared with PAs younger than 60 years.
      Variables included age, gender, year of PA graduation, duration of being a PA,
      and clinical activity by self-identified work location and specialty. RESULT: A
      total of 48,692 PAs participated in at least one census from 2005 through 2009.
      Approximately 5% (2,340) met the age criteria and were clinically active.
      Clinically active older PAs reported working a mean of 39 hours per week and were
      employed in a rural setting more often than their younger counterparts. Nearly
      one-half of older respondents reported their specialty to be primary care.
      CONCLUSION: Although the career span of a PA is only vaguely understood, a small
      but significant portion of clinicians appear to remain in the workforce into
      their seventh decade. They distinguish themselves by working proportionally more
      in primary care and nonurban areas than younger PAs. Older PAs may represent an
      American trend by remaining employed longer than historically observed. Gaps in
      the understanding of role behavior of PAs could be improved with longitudinal
      databases.

PMID- 22384758
TI  - State-of-the-art interventions in acute large-vessel ischemic stroke.

PMID- 22384759
TI  - Hypoparathyroidism. Meniere disease.

PMID- 22384760
TI  - A different kind of headache in a patient with migraines.

PMID- 22384761
TI  - Chromosomal microarray testing.

PMID- 22384762
TI  - Expiration date.

PMID- 22384763
TI  - Raynaud phenomenon.

PMID- 22384764
TI  - Development of early graphomotor skills in children with neurodevelopmental
      risks.
AB  - Drawing as an early form of a child's graphomotor skill is used as an element in
      the assessment of visual-motor coordination. Development of artistic expression
      is a precursor of the later development of writing that requires a high degree of
      coordination and precision. Children with perinatal impairment of the central
      nervous system and prematurely born children belong to a group of children with
      neurodevelopmental risk. Some of the possible results of this type of difficulty
      can be mild forms of motor disabilities. A retrospective study was conducted by
      archive review of children under the age of 3 hospitalized at University
      Department of Rheumatology, Physical Medicine and Rehabilitation, Sestre
      milosrdnice University Hospital Center. The aim was to determine the incidence
      ofgraphomotor difficulties in children with perinatal impairments of the central
      nervous system and prematurely born children. The study included 50 children aged
      12-36 months. The results showed 72% of the tested children to have drawings
      within the limits expected for their age, 13 children showed graphic abilities
      below the expectations for their age, while one child did not show functional use
      of pen. Literature indicates a common learning disability and difficulties with
      attention and fine motor skills in preschool and particularly in schoolchildren
      born with neurodevelopmental risk. This study therefore suggests that, despite
      good initial compensation in the early development ofgraphomotor skills, it is
      necessary to maintain follow-up procedures in order to prevent later difficulties
      in the development of graphomotor and writing skills.

PMID- 22384765
TI  - Transcranial Doppler monitoring of middle cerebral artery during verbal
      stimulation in aphasic patients.
AB  - Hemodynamic changes can be noninvasively real-time monitored in stroke patients
      by means of transcranial Doppler sonography (TCD). The aim of this pilot study
      was to assess hemodynamic changes in both middle cerebral arteries (MCA) in
      aphasic stroke patients by means of TCD during verbal stimulation. Eight aphasic
      patients with stroke in the territory of the left MCA were tested by modified
      Boston Diagnostic Aphasia Examination (BDAE) within 3 days of stroke onset. Both
      MCA were monitored simultaneously by means of TCD with 2 MHz probes. Basic MCA
      mean blood flow velocity (MBFV) values were assessed and monitored during verbal
      stimulation. Verbal stimulation was performed with 30 photos of objects for daily
      usage, arranged by function. The same test was performed in 16 right-handed
      healthy controls. In stroke patients, the mean MBFV were 56 cm/s in the left MCA
      and 56 cm/s in the right MCA. A mean 30% increase was observed in the left MCA
      and 22% in the right MCA. In healthy controls, a mean 21.7% increase was observed
      in the left MCA and 18% in the right MCA. A trend toward higher percentage of
      MBFV increase was observed in the left MCA during verbal stimulations in aphasic
      patients as compared to control subjects.

PMID- 22384766
TI  - Iodine intake and epidemiological characteristics of thyroid cancer: comparison
      between inland and littoral Croatia.
AB  - The aim of the study was to determine epidemiological characteristics of thyroid
      cancer in Dalmatia and Slavonia, to analyze regional differences in its
      incidence, and to determine whether iodine intake had an impact on the incidence.
      This epidemiological study was based on data published by the Croatian National
      Cancer Registry (CNCR) in the Croatian Health Service Yearbook and CNCR Bulletin.
      Data on 651 thyroid cancer patients operated on in Dalmatian hospitals between
      1997 and 2006 were analyzed. Control group consisted of thyroid cancer patients
      operated on in Slavonia (N = 498). Incidence rates recorded in Dalmatia were
      compared with those in Slavonia. Iodine intake was measured in elementary
      schoolchildren in the Split-Dalmatia and Osijek-Baranya Counties. Iodine
      excretion levels were measured in 131 children. In the 10-year period, the mean
      age-standardized incidence rate (ASR) of thyroid cancer was 9.32 per 100,000
      inhabitants in Dalmatia and 6.02 in Slavonia. The difference was statistically
      significant (P < 0.001). Incidence rates (World ASR, European ASR, crude
      incidence rate and research rates) showed an increase and were significantly
      higher in Dalmatia than in Slavonia. Patient sex structure showed the disease to
      be 4 times more common in women than in men. In Dalmatia sample, women accounted
      for 81.4% of all patients and papillary cancer accounted for 80.03% of all
      thyroid cancers. Median age of new patients was 50 in Dalmatia and 48 in
      Slavonia. Papillary cancer accounted for 63.7% of all patients in Slavonia.
      Follicular thyroid cancer accounted for 20.9% of patients in Slavonia and 12.4%
      in Dalmatia. Epidemiological characteristics of thyroid cancer in Dalmatia were
      found to be consistent with the characteristics of this cancer in iodine
      sufficient areas: papillary carcinoma was the most common type and the papillary
      to follicular ratio was 6.4:1. Follicular cancer accounted for 12.4% of the total
      number of patients. In Slavonia, the papillary form predominated, the papillary
      to follicular ratio was 3:1, and follicular cancer accounted for 20.88% of all
      patients. Median urinary iodine excretion in elementary schoolchildren was 23.6
      microg/dL in the Split-Dalmatia County and 28.1 microg/dL in the Osijek-Baranya
      County. The difference was not statistically significant (P < 0.050). In
      conclusion, the average iodine intake levels in Dalmatia and Slavonia were not
      the cause of the high thyroid cancer incidence in the 1997-2006 period. Improved
      thyroid cancer diagnosis may be one of the causes of the increased thyroid cancer
      incidence in Dalmatia.

PMID- 22384767
TI  - Post-stroke fatigue.
AB  - Post-stroke fatigue is still a relatively unexplored, often neglected condition.
      The fatigue often manifests as physical and mental lack of energy, and many
      patients mention fatigue as one of the most difficult sequels to which they have
      to adjust. Our aim was to assess the fatigue in 35 three-month post-stroke
      patients and its relation to personal and stroke-related factors, and to compare
      them with 35 age- and sex-matched healthy control subjects. The main outcome
      measures for the fatigue were Fatigue Severity Scale (FSS) and Multidimensional
      Fatigue Inventory (MFI-20). Barthel index was used for functional status
      assessment, while anxiety and depressive symptoms were evaluated using Hospital
      Anxiety and Depression Scale (HADS). Study results showed fatigue to be frequent
      (45%) and often severe. Post-stroke patients showed higher values of general
      fatigue dimensions, physical fatigue and reduced activity. The number of subjects
      reporting fatigue problems on the FSS and MFI-20 scales was significantly greater
      in the stroke group (16/35; 45%) than in the control group (4/35; 11%; chi2 =
      12.5; P < 0.001). Considering associations between fatigue and Barthel index
      score, age, sex, HADS-A (anxiety) and HADS-D (depression) scores, statistically
      significant associations were recorded between fatigue and anxiety (P = 0.01) and
      depression symptoms (P = 0.02). Global fatigue showed positive correlation with
      Barthel index score too (P = 0.01). Multivariate analysis showed that anxiety and
      depression symptoms could predict post-stroke fatigue (adjusted R2 = 0.556; P <
      0.05). Clinical trials and follow-up studies to find an effective treatment for
      patients with post-stroke fatigue are warranted.

PMID- 22384768
TI  - Human soluble TREM-1: lung and serum levels in patients with bacterial ventilator
      associated pneumonia.
AB  - Human soluble triggering receptor expressed on myeloid cells (sTREM-1) is a
      glycoprotein of the immunoglobulin superfamily. In normal lung tissue, sTREM-1 is
      selectively expressed in lung alveolar macrophages specialized for pathogen
      clearance and is up-regulated in the presence of bacteria and fungi. The aim of
      this study was to assess sTREM-1 levels in serum and lungs of patients with
      ventilator associated pneumonia (VAP) and to evaluate its potential diagnostic
      role. The study cohort included 31 patients meeting the criteria for VAP,
      including clinical, microbiological, radiological and laboratory findings in
      patients on mechanical ventilation for more than 48 hours and with Clinical
      Pulmonary Infection Score (CPIS) > 6. Serum and lung levels of sTREM-1 were
      obtained and tested for differences. The samples were analyzed using ELISA
      technique and the values were expressed in pg/mL. The samples for lung sTREM-1
      were obtained from direct bronchial lavage fluid and serum samples from
      peripheral blood. Differences were tested by Mann Whitney U test with P < 0.05
      considered significant. In patients with bacterial VAP, a statistically
      significant difference was found between serum and lung sTREM-1 levels (P <
      0.05), with very high levels of sTREM-1 recorded in lung samples (mean value 1565
      pg/mL). There was no statistically significant difference in pulmonary sTREM-1
      level between the polymicrobial and monomicrobial VAP groups. In conclusion,
      sTREM-1 is present in a high concentration in the lungs of patients with
      bacterial VAP. sTREM-1 levels can help in making the diagnosis of bacterial
      pneumonia as a standalone marker.

PMID- 22384769
TI  - Muscle weakness and other late complications of diabetic polyneuropathy.
AB  - Diabetic polyneuropathy is a progressive and irreversible disease, which leads to
      disability, changes in functioning in daily activities, and frequent falls and
      injuries in diabetes patients. It is one of the major reasons for the occurrence
      of foot ulceration and amputation of lower extremities. The aim of the study was
      to assess the relationship between muscle weakness and other complications of
      diabetic polyneuropathy. The study included 71 patients with
      electrophysiologically confirmed diabetic polyneuropathy. Through programmed
      questionnaires, our methodology encompassed examination of demographic, history
      (duration of diabetes), clinical (neuropathic score and examination) and
      functional characteristics (muscle strength, foot deformity, joint mobility).
      Muscle weakness was assessed using a semi-quantitative score. For the purpose of
      analysis, patients were divided into two groups: MS 1 (muscle strength)--patients
      with muscle strength score 0 (normal muscle strength) and 1 (moderate muscle
      strength), and MS 2--patients with score 2 (severe weakness) and 3 (complete loss
      of strength). MS 1 group consisted of 44 patients and MS 2 group of 27 patients.
      Significant differences were found in the duration of diabetes between groups MS
      1 and MS 2. The Neuropathy Disability Score was higher in group MS 2 (P = 0.001).
      Heel stand testing differed statistically significantly between MS 1 and MS 2
      groups (P < 0.001). High arch was observed in 80% of MS 2 patients. Duration of
      diabetes of more than 10 years and muscle weakness were found to be the factors
      influencing the degree of severe diabetic neuropathy.

PMID- 22384770
TI  - Efficiency of radiofrequency assisted uvulopalatopharyngoplasty in the treatment
      of snoring.
AB  - Snoring is an acoustic phenomenon, which is a consequence of vibrations of the
      soft tissue caused by partial obstruction of the upper breathing pathway while
      sleeping. It is estimated that 20% of men and 5% of women between 30 and 35 years
      of age snore and this rate increases to 50% of men and 30% of women over 60 years
      of age. The aim of this study was to evaluate the efficiency of radiofrequency
      assisted uvulopalatopharyngoplasty in the treatment of snoring by comparing
      snoring index and other polysomnography values before and after surgical
      treatment. The study included 22 patients (men 87% and women 13%), mean age 43.09
      +/-9.6 (range, 28-67) years, treated for obstructive sleep apnea syndrome at
      University Department of ENT and Head and Neck Surgery, Sestre milosrdnice
      University Hospital Center, Zagreb, during a 2-year period. Snoring was evaluated
      by preoperative and postoperative polysomnography at Department of
      Psychophysiology, Vrapce Psychiatric Hospital, Zagreb. Results were analyzed
      using Wilcoxon test. Postoperative reduction of snoring was statistically
      significant (P = 0.00052). Snoring index was decreased in 83% of patients,
      yielding a mean reduction of 83%. In 50% of patients, reduction of snoring index
      was over 95%. These results confirm the high efficiency of the procedure in the
      treatment of patients suffering from snoring.

PMID- 22384771
TI  - Risk factors for gross motor dysfunction of lower limbs in children.
AB  - The aim of this study was to identify risk factors for neurological development
      in children aged 1 to 3 years with a mild paraparesis form of motor development
      of lower extremities. Identification and follow-up of the neurorisk factors is
      important for early detection of neurodevelopmental deviations as well as for
      initiating early therapeutic treatments, which can improve the processes of brain
      plasticity and lead to recovery of the damaged function. Analysis of risk factors
      in children with paraparesis form of development revealed complicated pregnancy
      such as maternal diseases, fetal growth retardation or placental immaturity in
      48% of these children; 26% of children were born before or after the term, and
      34% had complications during delivery such as cesarean section or breech birth.
      In the present study, 80% of children with motor disabilities of lower
      extremities had Apgar index 10, 8% Apgar index 9, and only 12% had Apgar index
      lower than 8. Only 10% of 50 study children had normal ultrasound results,
      whereas cranial ultrasound abnormalities such as periventricular hemorrhage and
      intraventricular hemorrhage were recorded in 62% of the children.

PMID- 22384772
TI  - Management of patients with transient ischemic attack (TIA) at Sestre milosrdnice
      University Hospital Center.
AB  - Improved outcomes were observed in transient ischemic attack (TIA) patients after
      implementation of recommendations for stroke management and after multiple
      interventions such as public campaigns focused on raising awareness of stroke and
      reorganization of health services. The aim of this study was to describe
      reorganization of in-hospital services to improve the management of patients
      suspected of having TIA or stroke, and to validate these measures with patient
      outcomes. Data on 5219 patients examined between January 1 and December 31, 2008
      at emergency neurology outpatient department were analyzed. Patients were
      referred by general practitioners, emergency physicians, or were brought by
      relatives without being previously seen by health services staff. The emergency
      services department is intended to improve care for TIA patients, providing a
      short standardized clinical assessment followed by initiation of a comprehensive
      stroke prevention program. Demographic data, risk factors, stroke type, previous
      TIA history, ABCD2 scores and admission rates were analyzed. A total of 1057
      patients suspected of having stroke or TIA were examined. There were 447 patients
      with ischemic stroke (mean age 73 +/- 11 years, 196 males) and 99 patients with
      TIA (mean age 67 +/- 14 years, 55 males). Parenchymal hemorrhage was diagnosed in
      56 and subarachnoid hemorrhage in 49 patients, while 406 patients had nonspecific
      symptoms or other systemic or neurologic diseases. TIA preceded stroke in 29
      (6.5%) patients and 197 (44%) patients were examined for worsening of stroke
      symptoms (133 within 24 hours, 47 within 48 hours, and 17 within 7 days). The
      mean ABCD2 score was 2.95. In all examined patients, a comprehensive stroke
      prevention program was started; 427/447 (95%) strokes and 31/99 (31%) TIAs were
      hospitalized at neurology department. Four (4%) TIA patients developed stroke and
      were hospitalized, three of them after 2 days (ABCD2 score 3.4 and 5) and one
      after 7 days (ABCD2 score 5). Preventive measures resulted in a low number of
      strokes after TIA (< 7%), but a relatively high percentage (44%) of stroke
      patients ignored initial symptoms and sought medical attention after persistence
      or worsening of the symptoms.

PMID- 22384773
TI  - Minimal hepatic encephalopathy in patients with decompensated liver cirrhosis.
AB  - Minimal hepatic encephalopathy (mHE) is characterized by some minimal unspecific
      alterations of cerebral functions that can only be detected by neuropsychological
      or neurophysiological diagnostic tests, which dysfunctions nevertheless interfere
      with the patient's daily living. Early recognition of these impairments may
      prevent the progression or delay the development of the disease to overt hepatic
      encephalopathy. The aim of this study was to diagnose mHE in patients with
      decompensated liver cirrhosis. The study was conducted in 60 patients aged 40-65,
      divided into two groups: experimental group and control group. Patients in the
      experimental group were divided into Child-Pugh groups A, B or C: 53% were
      classified as Child-Pugh B and 47% as Child-Pugh C. Patients were tested using
      three neuropsychological tests: Mini Mental Score for quick assessment of
      cognitive status and two tests specific for mHE changes, Trail Making Test - Part
      A (TMT-A) and Symbol Digit Test (SDT). Electroencephalography (EEG) was performed
      in all patients. Limits for completing the test were set by using the formula
      X(control group) + 2 SD for TMT-A and X(control group) - 2 SD for SDT. All the
      three tests disclosed statistically significantly different results between the
      two groups. All patients with cirrhosis had some changes in EEG. Study results
      showed 80% of cirrhosis patients to have signs of mHE. The Child-Pugh score
      influenced performance on the neuropsychological tests. SDT more readily
      identified patients with mHE. Our findings pointed to the frequency of mHE and
      the importance of early diagnosis in the prevention of mHE progression to overt
      hepatic encephalopathy.

PMID- 22384774
TI  - Transurethral incision/resection of the prostate (TUIP/TURP) in operative
      treatment of repeated bladder outlet obstruction early after kidney
      transplantation.
AB  - The aim of the study was to assess the incidence and etiology of repeated bladder
      outlet obstruction (BOO) after kidney transplantation and to analyze the results
      of transurethral incision of the prostate/transurethral resection of the prostate
      (TUIP/TURP) in the early period after kidney transplantation. The study included
      24 male patients having undergone renal transplantation and early transurethral
      surgery for BOO in our institution between 2005 and 2011. TUIP or TURP was
      performed depending on the etiology of BOO. The indications for transurethral
      surgery were repeated urinary retention despite therapeutic attempts with alpha
      receptor antagonists, or repeated residual urine with renal transplant
      dysfunction and/or consequent urinary tract infection. Preoperative assessment
      included past medical history, clinical examination, PSA, volume of residual
      urine estimated with ultrasound, and urinary culture. Among 345 male patients
      having undergone renal transplantation, repeated BOO was noted in 24 patients.
      TUIP was performed in 19 and TURP in five patients. The mean age of our patients
      was 52 (range, 33-73) years and the mean time on dialysis 7.43 years (range, 4
      months to 25 years). The procedure was performed on the mean of day 16 (range, 14
      29) after transplantation and urethral catheter was removed on the mean of day
      3.3 (range, 2-9) after the procedure. The etiology of BOO was bladder neck
      contracture in nine and benign prostatic hyperplasia in 15 patients. In all
      patients, surgical procedures were performed without any complication.
      Restoration of urinary bladder function was complete in all patients. In
      conclusion, early transurethral treatment of repeated BOO is a safe procedure
      with excellent results following renal transplantation.

PMID- 22384775
TI  - Fifty-five years (1955-2010) of the Coagulation Section at Laboratory of
      Hematology, Sestre milosrdnice University Hospital, and its founder, hematologist
      Ljubomir Popovic.
AB  - The Coagulation Section at Laboratory of Hematology, Sestre milosrdnice
      University Hospital, Zagreb, was founded in 1955 by Ljubomir Popovic,
      hematologist and assistant at School of Medicine, University of Zagreb, in
      cooperation with hard-working laboratory technicians. Apart from papers on
      hematologic neoplasms, plasmacytoma and lymphoma, Ljubomir Popovic published a
      number of papers in the field of anticoagulant therapy with heparin and oral
      anticoagulants, some of which are also in use today. After Ljubomir Popovic left
      the Hospital in 1964, the Laboratory was run by Professor Nedjeljko Milic, head
      of the newly founded Division of Hematology. In 1968, the management of the
      Laboratory of Hematology was taken over by Biserka Raic, MS, medical biochemist,
      until her retirement in 2007. Great development in morphological and cytometric
      studies of blood and blood cells has been paralleled by continuous progress and
      almost dominating activities in the diagnosis of hemostasis disorders. In the
      1970s, Marko Koprcina, hematologist, and Biserka Raic introduced the then latest
      tests in practice at all Hospital departments. In that golden age of the
      Coagulation Section, M. Koprcina, B. Raic and their associates transferred their
      knowledge to all colleagues in the Hospital. Through that collaboration, high
      standards in the diagnosis of hemostasis disorders were achieved, from which the
      currently high level of clinical knowledge about coagulation disorders and their
      treatment has derived, making Sestre milosrdnice University Hospital one of the
      leading hospitals in this field in the country. By describing development of the
      Coagulation Section and the life of its founder Ljubomir Popovic, the authors
      tried to provide an answer to the following question: can today's clinicians
      still have a deciding role in laboratory development, considering that
      assessments of different phenomena are always initiated by an interested
      clinician who is trying to interpret and understand the nature of the disorder?
      This means that the clinician's place may still be in the laboratory, or else, it
      will become clear that the laboratory, as well as knowledge in general, has
      undergone such an expansion that the clinician is no longer able to run it by
      himself. It is our belief that the answer will assert itself through the survey
      of the history of the Coagulation Section at Laboratory of Hematology, Division
      of Hematology, and the lives of its founders and beneficiaries.

PMID- 22384776
TI  - Differential diagnosis of the scalp hair folliculitis.
AB  - Scalp hair folliculitis is a relatively common condition in dermatological
      practice and a major diagnostic and therapeutic challenge due to the lack of
      exact guidelines. Generally, inflammatory diseases of the pilosebaceous follicle
      of the scalp most often manifest as folliculitis. There are numerous infective
      agents that may cause folliculitis, including bacteria, viruses and fungi, as
      well as many noninfective causes. Several noninfectious diseases may present as
      scalp hair folliculitis, such as folliculitis decalvans capillitii,
      perifolliculitis capitis abscendens et suffodiens, erosive pustular dermatitis,
      lichen planopilaris, eosinophilic pustular folliculitis, etc. The classification
      of folliculitis is both confusing and controversial. There are many different
      forms of folliculitis and several classifications. According to the considerable
      variability of histologic findings, there are three groups of folliculitis:
      infectious folliculitis, noninfectious folliculitis and perifolliculitis. The
      diagnosis of folliculitis occasionally requires histologic confirmation and
      cannot be based solely on clinical appearance of scalp lesions. This article
      summarizes prominent variants of inflammatory diseases of the scalp hair follicle
      with differential diagnosis and appertaining histological features.

PMID- 22384777
TI  - Renal replacement therapies after abdominal aortic aneurysm repair--a review.
AB  - The objective of this review is to assess the incidence of postoperative acute
      renal failure that necessitates the application of hemofiltration and to
      determine the factors that influence the outcome in patients undergoing surgical
      repair of abdominal aortic aneurysm. In addition, the review aims to assess the
      outcomes of postoperative early hemofiltration as compared to late intensive
      hemofiltration. Different forms of renal replacement therapies for use in
      abdominal aortic aneurysm surgery patients are discussed. Electronic literature
      searches were performed using Pubmed, Medline, Embase, Sumsearch, Cinahil, The
      Cochrane Central Register of Controlled Trials and Excerpta Medica. The search
      identified 419 potentially eligible studies, of which 119 were excluded based on
      the title and abstract. Of the remaining 300 studies, full articles were
      collected and re-evaluated. Forty-five articles satisfied our inclusion criteria,
      of which only 12 were of the IA Level of evidence. The search results indicated
      that the underlying disease, its severity and stage, the etiology of acute renal
      failure, clinical and hemodynamic status of the patient, the resources available,
      and different costs of therapy might all influence the choice of the renal
      replacement therapy strategy. However, clear guidelines on renal replacement
      therapy duration are still lacking. Moreover, it is not known whether in acute
      renal failure patients undergoing abdominal aortic aneurysm surgery, renal
      replacement therapy modalities can eliminate significant amounts of clinically
      relevant inflammatory mediators. This review gives current information available
      in the literature on the possible mechanisms underlying acute renal failure and
      recent developments in continuous renal replacement treatment modalities.

PMID- 22384778
TI  - Undifferentiated carcinoma of the epididymis.
AB  - Epididymal tumors are uncommon and usually benign, with only 25% of them being
      malignant. Undifferentiated epididymal carcinoma in particular is extremely rare.
      We report on a 54-year-old male patient presented with right testicular pain and
      scrotal mass for the last 6 months. Laboratory investigations were unremarkable
      but epididymal biopsy result was epididymal undifferentiated carcinoma. Inguinal
      radical orchidectomy was performed and pathological examination of the surgical
      specimen confirmed the presence of undifferentiated carcinoma. Then, adjuvant
      chemoradiotherapy (four cycles of cisplatin-etoposide chemotherapy and
      radiotherapy) was administered. After four months, lung metastases were detected
      and three doses ifosfamide-Adriamycin chemotherapy were given, but the patient
      died due to the disease progression. Reports of epididymal undifferentiated
      carcinoma are extremely rare and the present report emphasizes the need of
      including epididymal undifferentiated carcinoma in the differential diagnosis of
      an epididymal mass.

PMID- 22384779
TI  - From recurrent peripheral facial palsy to multiple sclerosis.
AB  - Peripheral facial palsy is a clinical entity, which may be presented as the first
      symptom of multiple sclerosis (MS). Although MS is mostly a multifocal chronic
      inflammation of the central nervous system, peripheral nervous system can also be
      involved. Isolated cranial nerve palsies are rare and occur in 1.6% of MS
      patients. In this report, a case is presented of a 35-year-old woman who
      developed isolated seventh nerve palsy that was misdiagnosed as Bell's palsy.
      Despite recurrent peripheral facial palsy, positive cerebrospinal fluid finding
      and magnetic resonance imaging, the diagnosis of MS could only be confirmed when
      the patient developed other neurologic symptoms and when the criteria for
      dissemination in space were satisfied. In clinical presentation, the patient had
      only cranial nerve involvement, with complete recovery.

PMID- 22384780
TI  - Multiple intraplacental hematomas--Kline's hemorrhage.
AB  - A rare clinical case of intraplacental intervillous hemorrhage (Kline's
      hemorrhage) is presented. After delivery of a premature newborn (810 g/35 cm) in
      27th week of uncomplicated pregnancy, peripartum observation of the premature
      placenta (270 g, 16 x 16 x 1.8) suggested multiple intraplacental cavernae with
      semifluid blood and fresh coagula and fresh marginal (partial) placental
      abruption. The possible etiologic causes of recent microembolism include
      thrombophilia, microangiopathy diseases, antiphospholipid syndrome, disseminated
      intravascular coagulopathy and severe preeclampsia.

PMID- 22384781
TI  - Chronic, long-lasting, and untreated gout with concomitant dilated cardiomyopathy
      and exceptionally vast anasarca: case report.
AB  - Gout is the most common type of inflammatory arthritis in man caused by
      deposition of urate crystals into the joints as the result of elevated serum
      urate levels. A case of a 59-year-old patient with untreated, long-lasting gout
      and clinical manifestation of decompensated global dilated cardiomyopathy is
      presented. Examination revealed generalized pitting edema extending from both
      lower extremities to the sacrum, abdominal, and thoracic wall, with scrotal
      swelling and upper extremity involvement, an exceptionally vast generalized
      edema, i.e. anasarca. Proximal and distal interphalangeal joints of the hands and
      feet were swollen and deformed, with marked yellow tophi nodules. Laboratory
      studies revealed high serum uric acid concentration (546 micromol/L), decreased
      creatinine clearance (0.8 mL/s) and albumin concentration (27.4 g/L), as well as
      increased total urine protein mass (0.35 g/24 h). X-rays of the affected feet and
      fists showed punched-out lesions of the subchondral bone with overhanging bony
      margins in the first metatarsophalangeal, proximal, and distal interphalangeal
      joints of both hands. The extreme clinical presentation resolved upon intravenous
      administration of diuretics and pleurocentesis, followed by oral medications
      including furosemide, angiotensin-converting enzyme inhibitor, spironolactone and
      digoxin. Since serum urate level has been identified as an independent risk
      factor for the development of ischemic heart and chronic kidney disease,
      regulation of urate concentration is necessary, especially in patients diagnosed
      with gout.

PMID- 22384782
TI  - Penile metastases of prostate cancer.
AB  - Prostatic adenocarcinoma metastasizing to the penis is rare. A case of prostatic
      adenocarcinoma with metastases to the glans penis is presented. In this case,
      penile metastases developed nine years after the diagnosis of prostate cancer
      with regional lymph node metastasis.

PMID- 22384783
TI  - Mesencephalic form of meningoencephalitis in a patient with HLA-B51 Behcet's
      disease: case report.
AB  - This case report is a detailed description of the clinical, laboratory, imaging
      and therapeutic characteristics of the sixth patient with neuro-Behcet's disease
      reported by Bulgarian authors. The diagnosis was made in accordance with the
      international diagnostic criteria for Behcet's disease and was verified by skin
      biopsy. Therapeutic response was followed up by clinical and magnetic resonance
      imaging data for 6 months. Discussed are differences in the classical Behcet's
      disease presentation and other neuro-Behcet's disease cases found in Bulgaria.
      The current case supports the wide clinical heterogeneity of the disorder and the
      variety of therapeutic options.

PMID- 22384784
TI  - In vitro-to-in vivo predictions of drug-drug interactions involving multiple
      reversible inhibitors.
AB  - INTRODUCTION: Predictions of drug-drug interactions (DDIs) are commonly performed
      for single inhibitors, but interactions involving multiple inhibitors also
      frequently occur. Predictions of such interactions involving stereoisomer pairs,
      parent/metabolite combinations and simultaneously administered multiple
      inhibitors are increasing in importance. This review provides the framework for
      predicting inhibitory DDIs of multiple inhibitors with any combination of
      reversible inhibition mechanism. AREAS COVERED: The review provides an overview
      of the reliability of the in vitro determined reversible inhibition mechanism.
      Furthermore, the article provides a method to predict DDIs for multiple
      reversible inhibitors that allows substituting the inhibition constant (K(i))
      with an inhibitor affinity (IC(50)) value determined at S << K(M). EXPERT
      OPINION: A better understanding and the prediction methods of DDIs, resulting
      from multiple inhibitors, are important. The inhibition mechanism of a reversible
      inhibitor is often equivocal across studies and unreliable. Determination of the
      K(i) requires the assignment of reversible inhibition mechanism but in vitro-to
      in vivo prediction of DDI risk can be achieved for multiple inhibitors from
      estimates of the inhibitor affinity (IC(50)) only, regardless of the inhibition
      mechanism.

PMID- 22384785
TI  - Heterobimetallic chalcogenidometallate strands: synthesis, structure, magnetism,
      and conductivity.
AB  - Two salts with one-dimensional, SiS(2)-type telluridostannate chain anions
      {[MSnTe(4)](2-)}(n), Rb(2)[HgSnTe(4)] (2) and (NMe(4))(2)[MnSnTe(4)] (3), were
      prepared by the reactions of [SnTe](4-) anions with Hg(2+) or Mn(2+) ions in
      solution. We present the crystal structures of 2 and 3, as well as the magnetic
      properties of the previously reported Cs(+) analogue Cs(2)[MnSnTe(4)] (1).

PMID- 22384786
TI  - Atomic force microscopy in viscous ionic liquids.
AB  - Extracting quantitative information from amplitude-modulation atomic force
      microscopy (AM-AFM) in viscous ionic liquids is difficult because existing theory
      requires knowledge of the cantilever natural frequency, which cannot be measured
      in the absence of a resonance peak. We present a new model that describes
      cantilever dynamics in an overdamped medium (Q < 0.5) and derive the theory
      necessary to extract the stiffness and damping in highly viscous liquids. The
      proposed methodology is used to measure the solvation layers of an ionic liquid
      at a gold electrode.

PMID- 22384788
TI  - All-solid-state, semiconductor-sensitized nanoporous solar cells.
AB  - Despite the rapid increase in solar cell manufacturing capacity (~50 GW(p) in
      2011), maintaining this continued expansion will require resolving some major
      fabrication issues. Crystalline Si, the most common type of cell, requires a
      large energy input in the manufacturing process, which results in an energy
      payback time of years. CdTe/CdS thin film cells, which have captured around 10%
      of the global market, may not be sustainable for very large-scale use because of
      limited Te availability. Thus, research in this field is emphasizing cells that
      are energy efficient and inexpensive and use readily available materials. The
      extremely thin absorber (ETA) cell, the subject of this Account, is one of these
      new generation cells. Since the active light absorber in an ETA cell is no more
      than tens of nanometers thick, the direct recombination of photogenerated
      electrons and holes in the absorber should not compete as much with charge
      removal in the form of photocurrent as in thicker absorber materials. As a
      result, researchers expect that poorer quality semiconductors can be used in an
      ETA cell, which would expand the choice of semiconductors over those currently in
      use. We first describe the ETA cell, comparing and contrasting it to the dye
      sensitized cell (DSC) from which it developed and describing its potential
      advantages and disadvantages. We then explain the mechanism(s) of operation of
      the ETA cell, which remain controversial: different ETA cells most likely operate
      by different mechanisms, particularly in their photovoltage generation. We then
      present a general description of how we prepare ETA cells in our laboratory,
      emphasizing solution methods to form the various layers and solution treatments
      of these layers to minimize manufacturing costs. This is followed by a more
      specific discussion of the various layers and treatments used to make and
      complete a cell with emphasis on solution treatments that are important in
      optimizing cell performance and explaining the possible modes of action of each
      of these treatments. Finally, we show how ETA cells have improved over the years,
      their present efficiencies, our expectations for the future, and the challenges
      that we foresee to fulfill these expectations.

PMID- 22384789
TI  - Pharmacophore mapping and in silico screening to identify new potent leads for
      A(2A) adenosine receptor as antagonists.
AB  - A(2A) adenosine receptor (AR) antagonists play an important role in
      neurodegenerative diseases like Parkinson's disease. A 3D-QSAR study of A(2A) AR
      antagonists, was taken up to design best pharmacophore model. The pharmacophoric
      features (ADHRR) containing a hydrogen bond acceptor (A), a hydrogen bond donor
      (D), a hydrophobic group (H) and two aromatic rings (R), is projected as the best
      predictive pharmacophore model. The QSAR model was further treated as a template
      for in silico search of databases to identify new scaffolds. The binding patterns
      of the leads with A(2A) AR are analysed using docking studies and novel potent
      ligands of A(2A) AR are projected.

PMID- 22384790
TI  - Laser CO2 versus radiotherapy in treatment of keloid scars.
AB  - Keloids and hypertrophic scars are quite common diseases that can occur after any
      kind of wound and skin inflammation in predisposed individuals. Despite their
      benign nature, they can be aesthetically disabling and they are often accompanied
      by unpleasant symptoms such pain, burning and itching. Several approaches have
      been tried but most of them with poor results. Ablative fractional CO(2) laser
      seems to be an encouraging approach in treatment of keloids and hypertrophic
      scars, not only for its efficacy, but also for its low harmfulness. Radiotherapy
      following surgical excision is commonly used to treat these scars, but an
      increased incidence of different kinds of cancer from radiation has been
      demonstrated in several cases. Compared to radiotherapy, the use of CO(2) laser
      after surgical excision of keloids has shown great results with no recurrence and
      without the risk of carcinogenesis.

PMID- 22384791
TI  - Three-dimensional representation of the human cochlea using micro-computed
      tomography data: presenting an anatomical model for further numerical
      calculations.
AB  - CONCLUSION: We present a complete geometric model of the human cochlea, including
      the segmentation and reconstruction of the fluid-filled chambers scala tympani
      and scala vestibuli, the lamina spiralis ossea and the vibrating structure
      (cochlear partition). OBJECTIVE: Future fluid-structure coupled simulations
      require a reliable geometric model of the cochlea. The aim of this study was to
      present an anatomical model of the human cochlea, which can be used for further
      numerical calculations. METHODS: Using high resolution micro-computed tomography
      (uCT), we obtained images of a cut human temporal bone with a spatial resolution
      of 5.9 um. Images were manually segmented to obtain the three-dimensional
      reconstruction of the cochlea. RESULTS: Due to the high resolution of the uCT
      data, a detailed examination of the geometry of the twisted cochlear partition
      near the oval and the round window as well as the precise illustration of the
      helicotrema was possible. After reconstruction of the lamina spiralis ossea, the
      cochlear partition and the curved geometry of the scala vestibuli and the scala
      tympani were presented. The obtained data sets were exported as standard
      lithography (stl) files. These files represented a complete framework for future
      numerical simulations of mechanical (acoustic) wave propagation on the cochlear
      partition in the form of mathematical mechanical cochlea models. Additional
      quantitative information concerning heights, lengths and volumes of the scalae
      was found and compared with previous results.

PMID- 22384792
TI  - Identification of domains in protein structures from the analysis of
      intramolecular interactions.
AB  - The subdivision of protein structures into smaller and independent structural
      domains has a fundamental importance in understanding protein evolution and
      function and in the development of protein classification methods as well as in
      the interpretation of experimental data. Due to the rapid growth in the number of
      solved protein structures, the need for devising new accurate algorithmic methods
      has become more and more urgent. In this paper, we propose a new computational
      approach that is based on the concept of domain as a compact and independent
      folding unit and on the analysis of the residue-residue energy interactions
      obtainable through classical all-atom force field calculations. In particular,
      starting from the analysis of the nonbonded interaction energy matrix associated
      with a protein, our method filters out and selects only those specific subsets of
      interactions that define possible independent folding nuclei within a complex
      protein structure. This allows grouping different protein fragments into energy
      clusters that are found to correspond to structural domains. The strategy has
      been tested using proper benchmark data sets, and the results have shown that the
      new approach is fast and reliable in determining the number of domains in a
      totally ab initio manner and without making use of any training set or knowledge
      of the systems in exam. Moreover, our method, identifying the most relevant
      residues for the stabilization of each domain, may complement the results given
      by other classification techniques and may provide useful information to design
      and guide new experiments.

PMID- 22384793
TI  - Minnesota Multiphasic Personality Inventory-2 revised form Symptom Validity Scale
      Revised (MMPI-2-RF FBS-r; also known as Fake Bad Scale): psychometric
      characteristics in a nonlitigation neuropsychological setting.
AB  - This study examined fundamental psychometric characteristics of the Symptom
      Validity Scale-Revised (FBS-r) in a nonforensic sample of 303 neuropsychological
      referrals. FBS-r had a reliability (internal consistency) of .747 and two higher
      order factoral dimensions (Somatic Complaints and Optimism/Virtue). FBS-r had a
      discordant factor structure: Optimism/Virtue (7 items) was negatively related to
      Somatic Complaints (21 items) and undercut FBS-r measurement consistency
      (reliability). FBS-r scores, which purportedly reflect symptom exaggeration, are
      affected by as much as 23 T-score points on test items that are negatively
      related to symptom reporting. These data suggest that the FBS-r produces
      ambiguous scores reflecting two underlying dimensions that warrant additional
      research.

PMID- 22384795
TI  - Recolonization of group B Streptococcus (GBS) in women with prior GBS genital
      colonization in pregnancy.
AB  - OBJECTIVE: The purpose of the study is to evaluate the incidence of women with
      prior GBS genital colonization who have recolonization in subsequent pregnancies.
      METHODS: This is a retrospective, cohort study of patients with a prior GBS
      genital colonization in pregnancy and a subsequent pregnancy with a recorded GBS
      culture result, from January 2000 through June 2007. Documentation of GBS status
      was through GBS culture performed between 35 to 37 weeks gestation. Exclusion
      criteria included pregnancies with unknown GBS status, patients with GBS
      bacteriuria, women with a previous neonate with GBS disease and GBS finding prior
      to 35 weeks. Data was analyzed using SPSS 15.0. The sample proportion of subjects
      with GBS genital colonization and its confidence interval were computed to
      estimate the incidence rate. Logistic regression was performed to assess
      potential determinants of GBS colonization. Regression coefficients, odds ratios
      and associated confidence intervals, and p-values were reported, with significant
      results reported. RESULTS: There were 371 pregnancies that met the test criteria.
      There were 151 subsequent pregnancies with GBS genital colonization and 220
      without GBS recolonization. The incidence of GBS recolonization on patients with
      prior GBS genital colonization was 40.7% (95% confidence interval 35.7-45.69%).
      The incidence rate for the sample was significantly larger than 30% (p < .001),
      which is the estimated incidence rate for all pregnant women who are GBS carriers
      regardless of prior history. CONCLUSION: These results suggest that patients with
      a history of GBS are at a significantly higher risk of GBS recolonization in
      subsequent pregnancies.

PMID- 22384794
TI  - Molecular mechanisms of metabolic reprogramming in proliferating cells:
      implications for T-cell-mediated immunity.
AB  - To engage in proliferation, cells need to increase their biomass and replicate
      their genome. This process presents a substantial bioenergetic challenge:
      proliferating cells must increase ATP production and acquire or synthesize raw
      materials, including lipids, proteins and nucleic acids. To do so, proliferating
      cells actively reprogramme their intracellular metabolism from catabolic
      mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis and other anabolic
      pathways. This metabolic reprogramming, which directs nutrient uptake and
      metabolism during cell activation and proliferation, is under the control of
      specific signal transduction pathways. The underlying molecular mechanisms of
      cell metabolism reprogramming and their relevance to physiology and disease are
      currently under intense study. Several reports have uncovered the mechanisms of
      metabolic reprogramming that drive high rates of cell proliferation in cancer.
      Some recent studies have elucidated the physiological role of metabolic
      reprogramming during T-cell activation, differentiation and trafficking, which
      are potentially relevant to inflammatory disorders. This review describes the
      impact of metabolic reprogramming on the pathogenesis of cancer and the
      physiology of T-cell-mediated immune responses, with an emphasis on the
      phosphatidyl inositol 3-kinase-serine/threonine kinase-mammalian target of
      rapamycin pathway and the recently discovered metabolic processes regulated by
      nuclear factor-kappaB. These discoveries will hopefully translate into a better
      understanding of the role of metabolic reprogramming as a key regulator of T-cell
      mediated immune responses and offer novel, immune-based therapeutic approaches.

PMID- 22384796
TI  - Barriers to the utilization of thrombolysis for acute ischaemic stroke.
AB  - WHAT IS KNOWN AND OBJECTIVE: Thrombolysis is currently the only evidence-based
      pharmacological treatment available for acute ischaemic stroke (AIS); however,
      its current utilization is suboptimal (administered to <3% of AIS patients). The
      aim of this article was to identify the potential barriers to the use of
      thrombolysis via a review of the available literature. METHODS: Medline, Embase,
      International Pharmaceutical Abstracts and Google Scholar were searched to
      identify relevant original articles, review papers and other literature published
      in the period 1995-2011. RESULTS AND DISCUSSION: Several barriers to the
      utilization of thrombolysis in stroke have been identified in the literature and
      can be broadly classified as 'preadmission' barriers and 'post-admission'
      barriers. Preadmission barriers include patient and paramedic-related factors
      leading to late patient presentation for treatment (i.e. outside the therapeutic
      time window for the administration of thrombolysis). Post-admission barriers
      include in-hospital factors, such as suboptimal triage of stroke patients and
      inefficient in-hospital acute stroke care systems, a lack of appropriate
      infrastructure and expertise to administer thrombolysis, physician uncertainty in
      prescribing thrombolysis and difficulty in obtaining informed consent for
      thrombolysis. Suggested strategies to overcome these barriers include public
      awareness campaigns, prehospital triage by paramedics, hospital bypass protocols
      and prenotification systems, urgent stroke-unit admission, on-call
      multidisciplinary acute stroke teams, urgent neuroimaging protocols, telestroke
      interventions and risk-assessment tools to aid physicians when considering
      thrombolysis. Additionally, greater pharmacists' engagement is warranted to help
      identify the people at risk of stroke and support preventative strategies, and
      provide the public with information regarding the recognition of stroke, as well
      as facilitate the access and use of thrombolysis. WHAT IS NEW AND CONCLUSION: The
      most effective interventions appear to be those comprising several strategies and
      those that target more than one barrier simultaneously. Therefore, optimal
      utilization of thrombolysis requires a systematic, integrated multidisciplinary
      approach across the continuum of acute care.

PMID- 22384797
TI  - Neonatal cyanosis due to a new (G)gamma-globin variant causing low oxygen
      affinity: Hb F-Sarajevo [(G)gamma102(G4)Asn->Thr, AAC>ACC].
AB  - A baby girl, born at term, presented with severe cyanosis and received oxygen
      supplementation. Consecutive arterial blood gas analysis showed a pronounced
      right shift of the saturation curve, suggesting the presence of a hemoglobin (Hb)
      variant. A new (G)gamma-globin variant was detected, namely HBG2:c.308G, which we
      have named Hb F-Sarajevo, the city from where the baby's parents originate. This
      A to C transversion exists in cis to the common (A)gamma(T) and the resulting
      mutant Hb molecule exhibits very low oxygen affinity and cooperativity. Its
      analogue in the beta-globin gene is Hb Kansas [beta102(G4)Asn->Thr, AAC>ACC].

PMID- 22384798
TI  - Dimethylformamide improves the in vitro characteristics of thawed stallion
      spermatozoa reducing sublethal damage.
AB  - A total of 42 ejaculates were used in the experiment; six ejaculates per
      stallion, obtained from seven Pure Spanish stallions (PRE), were split and frozen
      in freezing media with different concentrations and combinations of
      cryoprotectant (CPA): (i) Caceres (skim milk based extender) containing 2.5%
      glycerol (2.5GL), (ii) Caceres containing 1.5% glycerol and 1.5%
      dimethylformamide (1.5%GL-1.5%DMFA), (iii) Caceres extender supplemented with
      1.5% glycerol and 2.5% dimethylformamide (1.5%GL-2.5%DMFA) and (iv) Caceres
      extender supplemented with 4% dimethylformamide (4%DMFA). After at least 4 weeks
      of storage in liquid nitrogen (LN), straws were thawed and semen analysed by
      computer-assisted sperm analysis and flow cytometry (membrane lipid architecture
      (Merocyanine 540), integrity and sublethal damage (YoPro-1) and mitochondrial
      membrane potential (JC-1)). After thawing, better results were observed in
      samples frozen in 4%DMFA or in combinations of 1.5%GL-2.5%DMFA, in fact total
      motility increased by 16% in the 4%DMFA group compared to 2.5%GL (P < 0.05).
      Also, there was an increment in the percentage of progressive motile sperm in the
      1.5%GL-2.5%DMFA group (9.8% 2.5GL vs 19% in the 1.5%GL-2.5%DMFA group p < 0.05);
      also, samples frozen in the 4%DMFA group had more intact (YoPro-1 negative) sperm
      post-thawing, 29.3% in 2.5%GL vs 36.7% in 4%DMFA group (p < 0.05). Membrane lipid
      architecture was not affected by any of the cryoprotectants tested, while samples
      frozen in 4%DFMA had a lower percentage of mitochondria with lower membrane
      potential. It is concluded that DMFA improves the outcome of cryopreservation of
      stallion spermatozoa mainly reducing sublethal cryodamage.

PMID- 22384799
TI  - Association of automated data collection and data completeness with outcomes of
      intensive care. A new customised model for outcome prediction.
AB  - BACKGROUND: The Finnish Intensive Care Consortium coordinates a national
      intensive care benchmarking programme. Clinical information systems (CISs) that
      collect data automatically are widely used. The aim of this study was to explore
      whether the severity of illness-adjusted hospital mortality of Finnish intensive
      care unit (ICU) patients has changed in recent years and whether the changes
      reflect genuine improvements in the quality of care or are explained by changes
      in measuring severity of illness. METHODS: We retrospectively analysed data
      collected prospectively to the database of the Consortium. During the years 2001
      2008, there were 116,065 admissions to the participating ICUs. We excluded
      readmissions, cardiac surgery patients, patients under 18 years of age and those
      discharged from an ICU to another hospital's ICU. The study population comprised
      85,547 patients. The Simplified Acute Physiology Score II (SAPS II) was used to
      measure severity of illness and to calculate standardised mortality ratios (SMRs,
      the number of observed deaths divided by the number of expected deaths). RESULTS:
      The overall hospital mortality rate was 18.4%. The SAPS II-based SMRs were 0.74
      in 2001-2004 and 0.64 in 2005-2008. The severity of illness-adjusted odds of
      death were 24% lower in 2005-2008 than in 2001-2004. One fifth of this
      computational difference could be explained by differences in data completeness
      and the automation of data collection with a CIS. CONCLUSION: The use of a CIS
      and improving data completeness do decrease severity-adjusted mortality rates.
      However, this explains only one fifth of the improvement in measured outcomes of
      intensive care in Finland.

PMID- 22384800
TI  - Neuropilin-2 expression in cancer.
AB  - AIMS: Neuropilin-2 is a coreceptor for vascular endothelial growth factor family
      members. Blockade of neuropilin-2 is able to suppress lymphogenous metastasis in
      preclinical models. The aim of this study was to validate a protocol for the
      evaluation of neuropilin-2 protein expression in situ, by comparison with in-situ
      hybridization, western blotting, and mRNA expression levels. METHODS AND RESULTS:
      Immunohistochemistry was performed on normal human tissues, and whole sections
      for 79 primary non-small-cell lung carcinomas, 65 primary breast carcinomas, 79
      primary colorectal cancers, and 52 metastases. Neuropilin-2 expression was
      observed in lymphatic and blood vessels from all normal and malignant tissues
      examined. In addition, 32% of primary non-small-cell lung carcinomas, 15% of
      primary breast carcinomas and 22% of primary colorectal cancers showed tumour
      cell expression. Fifty-five primary and nine secondary malignant melanomas were
      also examined for neuropilin-2 expression by in-situ hybridization. All showed
      vascular expression, and 85% of primary malignant melanomas showed tumour cell
      expression. CONCLUSIONS: In the majority of lung, breast and colorectal cancers,
      the effects of anti-neuropilin-2 are likely to be restricted to the vasculature.
      These results will assist in pharmacokinetic evaluations, tolerability
      assessments and the choice of setting to evaluate the activity of anti-neuropilin
      2 therapies.

PMID- 22384801
TI  - Is there a positive relationship between molar incisor hypomineralisations and
      the presence of dental caries?
AB  - OBJECTIVE: This epidemiological study aimed to compare the caries experience in
      10-year-olds with and without molar incisor hypomineralisation (MIH). METHODS:
      About 693 children from an ongoing birth cohort study (GINIplus10) were examined
      for caries lesions to determine the DMF index. Furthermore, enamel
      hypomineralisation (EH) was scored on all permanent teeth/surfaces, according to
      the criteria of the European Academy of Paediatric Dentistry. Children with EH
      were categorised into those with a minimum of one EH in the permanent dentition
      (MIH/1), with EH on at least one-first permanent molar (MIH/1A), on at least one
      first permanent molar and permanent incisor (MIH/1B), and on other permanent
      teeth (MIH/1C). RESULTS: The mean caries experience was 0.4 (SD 0.9) DMFT.
      Existence of MIH/1, MIH/1A, MIH/1B, and MIH/1C was determined in 36.5%, 14.7%,
      9.4%, and 21.8% of all children. The corresponding DMFT values were the
      following: no MIH: 0.3 (SD 0.8); MIH/1: 0.5 (SD 0.9); MIH/1A: 0.5 (SD 0.9);
      MIH/1B: 0.4 (SD 0.9); and MIH/1C: 0.4 (SD 0.9) DMFT. No significant differences
      were found between all groups. CONCLUSIONS: There was no relationship between the
      presence of EH/MIH and caries in 10-year-olds. A ratio of one EH-associated
      defect to two caries lesions indicates that both conditions are prevalent and
      influence the oral health status of 10-year-old children from Munich, Germany.

PMID- 22384802
TI  - Determination of the lithium binding site in inositol monophosphatase, the
      putative target for lithium therapy, by magic-angle-spinning solid-state NMR.
AB  - Inositol monophosphatase (IMPase) catalyzes the hydrolysis of inositol
      monophosphate to inorganic phosphate and inositol. For this catalytic process to
      occur, Mg(2+) cations must exist in the active site. According to the inositol
      depletion hypothesis, IMPase activity is assumed to be higher than normal in
      patients suffering from bipolar disorder. Treatment with Li(+), an inhibitor of
      IMPase, reduces its activity, but the mechanism by which lithium exerts its
      therapeutic effects is still at a stage of conjecture. The  Escherichia coli 
      SuhB gene product possesses IMPase activity, which is also strongly inhibited by
      Li(+). It has significant sequence similarity to human IMPase and has most of its
      key active-site residues. Here we show that by using (7)Li magic-angle-spinning
      solid-state NMR spectroscopy, including {(13)C}(7)Li dipolar recoupling
      experiments, the bound form of lithium in the active site of wild-type  E. coli 
      SuhB can be unambiguously detected, and on the basis of our data and other
      biochemical data, lithium binds to site II, coupled to aspartate residues 84, 87,
      and 212.

PMID- 22384803
TI  - A critical appraisal of motivational interviewing within the field of alcohol
      misuse.
AB  - A critical appraisal of the evidence that supports efficacy of the brief
      intervention, motivational interviewing (MI), within the field of alcohol misuse,
      was made. In order to undertake this appraisal the author will focus on a review
      of the concept of MI prior to considering the efficacy for MI within the specific
      field of alcohol misuse.

PMID- 22384804
TI  - Pulmonary embolism secondary to metastatic renal cell carcinoma.

PMID- 22384805
TI  - Enzymes to die for: exploiting nucleotide metabolizing enzymes for cancer gene
      therapy.
AB  - Suicide gene therapy is an attractive strategy to selectively destroy cancer
      cells while minimizing unnecessary toxicity to normal cells. Since this idea was
      first introduced more than two decades ago, numerous studies have been conducted
      and significant developments have been made to further its application for
      mainstream cancer therapy. Major limitations of the suicide gene therapy strategy
      that have hindered its clinical application include inefficient directed delivery
      to cancer cells and the poor prodrug activation capacity of suicide enzymes. This
      review is focused on efforts that have been and are currently being pursued to
      improve the activity of individual suicide enzymes towards their respective
      prodrugs with particular attention to the application of nucleotide metabolizing
      enzymes in suicide cancer gene therapy. A number of protein engineering
      strategies have been employed and our discussion here will center on the use of
      mutagenesis approaches to create and evaluate nucleotide metabolizing enzymes
      with enhanced prodrug activation capacity and increased thermostability. Several
      of these studies have yielded clinically important enzyme variants that are
      relevant for cancer gene therapy applications because their utilization can serve
      to maximize cancer cell killing while minimizing the prodrug dose, thereby
      limiting undesirable side effects.

PMID- 22384806
TI  - Biodistribution and safety assessment of bladder cancer specific recombinant
      oncolytic adenovirus in subcutaneous xenografts tumor model in nude mice.
AB  - BACKGROUND: The previous works about safety evaluation for constructed bladder
      tissue specific adenovirus are poorly documented. Thus, we investigated the
      biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad
      PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing
      meaningful information prior to embarking on human clinical trials. MATERIALS AND
      METHOD: Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA
      AR were constructed with bladder tissue specific UroplakinII(UPII) promoter to
      induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was
      inserted at upstream of promoter to enhance the function of promoter. Based on
      the cytopathic and anti-tumor effect of bladder cancer, these CRADs were
      intratumorally injected into subcutaneous xenografts tumor in nude mice. We then
      determined the toxicity through general health and behavioral assessment, hepatic
      and hematological toxicity evaluation, macroscopic and microscopic postmortem
      analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR
      and Western blot. Virus replication and distribution were examined with APU-LUC
      administration and Luciferase Assay. RESULTS: General assessment and body weight
      of the animals did not reveal any alteration in general behavior. The
      hematological alterations of groups which were injected with 5x10(8) pfu or
      higher dose (5x10(9) pfu) of APU-E1A and APU-E1A-AR showed no difference in
      comparison with PBS group, and only slight increased transaminases in contrast to
      PBS group at 5x10(9) pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene
      did not disseminate to organs outside of xenograft tumor. Virus replication was
      not detected in other organs beside tumor according to Luciferase Assay.
      CONCLUSIONS: Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A
      appear safe with 5x10(7) pfu and 5x10(8) pfu intratumorally injection in mice,
      without any discernable effects on general health and behavior.

PMID- 22384807
TI  - Can medical education in poor rural areas be cost-effective and sustainable: the
      case of the Ateneo de Zamboanga University School of Medicine.
AB  - INTRODUCTION: This study examined the hypothesis that a medical school in a low
      resource setting, based on volunteer faculty, can be sustainable and associated
      with improvement in medical workforce and population health outcomes. METHODS:
      Using a retrospective case study approach, this study described the formation of
      the Ateneo de Zamboanga University School of Medicine (ADZU SOM) in Zamboanga
      province, Mindanao, Philippines. The principal outcome measures were the number
      of graduated students practicing as physicians in the Philippines, the number of
      local municipalities with doctors, and changes in the provincial infant mortality
      rate since the School's inception. RESULTS: Since the first 15 graduates in 1999,
      by 2011 more than 160 students had successfully graduated with over 80%
      practicing in the local underserved regions. This compares with a national
      average of 68% of Philippine medical graduates practicing overseas. There has
      been a 55% increase (n=20 to 31) in the number of municipalities in Zamboanga
      with a doctor. Since the ADZU SOM's inception in 1994, the infant mortality rate
      in the region has decreased by approximately 90%, compared with a national change
      of approximately 50% in the same time period. The School has only three employees
      because all teachers continue to work as volunteer clinicians from the local
      health services. CONCLUSIONS: These results can encourage governments and
      communities around the world to consider adopting a socially accountable approach
      to medical education as a cost-effective strategy to improve medical workforce in
      underserved areas.

PMID- 22384808
TI  - Examining variations in health within rural Canada.
AB  - INTRODUCTION: Differences in health between urban and rural areas of Canada are
      well documented. Canadian rural communities are remarkably heterogeneous in terms
      of social, economic, and geographic characteristics. There is reason to believe
      that there is also considerable heterogeneity in health within rural Canada but
      existing literature has not given this adequate consideration. This article
      describes heterogeneity in health along the urban-rural continuum, both between
      and within categories of rural areas. Factors that may explain observed
      variations are then examined. METHODS: The study population included all adult
      (>18 years) respondents on the Canadian Community Health Survey Cycle 1.1, linked
      to census subdivision-level data from the corresponding Canadian Census. Study
      areas were classified according to Metropolitan Influenced Zones (MIZ), which
      group rural areas based on their degree of connectivity with nearby urban areas.
      Dichotomized Health Utilities Index (HUI) scores were the outcome variable.
      Random-intercept logistic regression models investigated the associations of HUI
      with individual and area characteristics. To describe between-area variation in
      health, the proportion of the total variation accounted for by the area random
      effect (the intra-class correlation coefficient [ICC]) was estimated. To aid
      interpretation of the magnitude of the effect of area relative to other variables
      in the models, the ICC was also expressed as a median odds ratio (MOR), or the
      median amount by which the probability of disability will change for an
      individual who moves from one area to another. RESULTS: On a descriptive level,
      poorer health was observed in more remote rural areas, but the size of estimated
      effects for categories of rural areas was generally small compared with effects
      of other individual and area variables, and with the degree of heterogeneity
      between areas. The composition of rural areas is important in order to understand
      patterns in health. Individual income, education, and employment, and area
      characteristics such as Francophone or Aboriginal populations, and migration
      patterns help explain the gradient in health by MIZ, but considerable
      heterogeneity in health within categories of MIZ remains. In models stratified by
      MIZ, significant between-area heterogeneity was observed in all models, with MORs
      ranging from 1.18 to 1.53. CONCLUSION: It was observed that heterogeneity in
      health among rural areas is substantial, and generally larger than the effect of
      rurality, itself, on health. More attention is needed to understand the
      characteristics of Canada's heterogeneous rural communities, and the different
      processes by which disparities in health emerge and persist. The findings suggest
      that a focus on rurality alone, emphasizing urban versus rural disparities, or
      even continuum-based approaches like MIZ, may be less informative than finding
      ways to classify and examine different types of rural areas according to factors
      relevant to health.

PMID- 22384809
TI  - Dermatofibromas treated with pulsed dye laser: Clinical and dermoscopic outcomes.
AB  - Dermatofibroma (DF), a common benign skin tumour, sometimes requires treatment
      either because of cosmetic concern or for associated symptoms. However, no
      effective treatment with optimal cosmetic outcomes has been reported. An
      effective and safe therapeutic option could be treatment with pulsed dye laser
      (PDL). Twenty-two DFs in 15 patients were treated with PDL at 595-nm wavelength,
      using a spot size of 7 mm, a pulse duration of 2 ms and a fluence of 11 J/cm(2)
      with 2 or 3 stacked pulses. Clinical and dermoscopic photographs were taken
      before and after therapy. Global clinical improvement was higher than 50% in 12
      lesions. Patient satisfaction assessment showed 73% of patients as satisfied or
      very satisfied. All lesions showed changes from the previous dermoscopic pattern.
      We consider that PDL could be a safe, palliative treatment as it is well accepted
      by patients and has a better cosmetic outcome than surgical excision.

PMID- 22384810
TI  - Silencing of the integrin-linked kinase gene induces the apoptosis in ovarian
      carcinoma.
AB  - CONTEXT: Integrin-linked kinase (ILK), a multidomain focal adhesion protein
      serine/threonine kinase, plays an essential role in ovarian carcinoma. There are
      reports that the expression and activity of ILK are increased in ovarian cancer.
      OBJECTIVE: To test the hypothesis that ILK pathway mediates the apoptosis of
      ovarian carcinoma SKOV3 cell influencing the cell survival, we performed these
      studies. MATERIALS AND METHODS: We applied lentivirus transfection, 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), apoptotic proteins
      expressions assay, and Hoechst to study our hypothesis. RESULTS: We found that
      silencing of the ILK increases the cell cytotoxic, growth inhibition, and
      apoptosis. Moreover, after blocking the activation of ILK with ILK shRNA, up
      regulation of pro-apoptotic bax expression and down-regulation of the anti
      apoptotic bcl-2 expression were found in ovarian cancer SKOV3 cell line. These
      were associated with an increasing cleaved caspase-3 activity and chromatin
      condensation of cell nuclear. Furthermore, the expressions of fas and fas ligand
      (fasL), belonging to the tumor necrosis factor family and controlling the cell
      apoptosis, were also enhanced. CONCLUSIONS: Thus, these findings indicate that
      both the intrinsic pathway and the extrinsic death receptor pathway are involved
      in the process that silencing of the ILK gene induces the apoptosis in ovarian
      carcinoma SKOV3 cell.

PMID- 22384811
TI  - AFM imaging of milk casein micelles: evidence for structural rearrangement upon
      acidification.
AB  - Milk casein micelles are natural association colloids that we all encounter in
      everyday life, yet we still lack an accurate description of their internal
      structure and the interactions that stabilize it. In this letter, we provide for
      the first time detailed images of intact casein micelles as obtained through
      atomic force microscopy under liquid conditions close to physiological. The
      micelles appear as heterogeneous raspberry-like particles, which is consistent
      with a hierarchical/spongelike structure made of connected 10-40 nm dense casein
      regions. Upon in situ acidification to pH 5, the micelles decrease in size and
      lose their surface heterogeneities, indicating that this structure is highly
      sensitive to variations in mineral content and caseins net charge.

PMID- 22384812
TI  - JNK Activation by Up-Regulation of iNOS on Cholesterol Accumulation Limits
      Neurogenesis and Induces Region-Specific DNA Damage Responses in the
      Subventricular Zone of NPC Mice.
AB  - Abstract Aims: We explore the region-specific impact of nitric oxide (NO) on
      adult neural stem cell (aNSC) niches with regard to neurogenesis and NSC damage
      and investigate the underlying mechanisms in Niemann-Pick disease type C (NPC)
      mice. Results: Among the two anatomical stem-cell niches of the brain,
      subventricular zone (SVZ)-derived aNSCs enhanced c-Jun N-terminal kinase (JNK)
      activity because of excessive NO production by the cholesterol accumulation.
      Activated JNK interacts with gammaH2AX, a marker for DNA damage; however, almost
      none of the aNSCs in the dentate gyrus (DG) showed either JNK signaling
      activation or abundant DNA damage. SVZ-derived aNSCs were protected from DNA
      damage by the treatment of Nomega-nitro-L-arginine methyl ester (L-NAME), a NO
      synthase (NOS) inhibitor, both in vitro and in vivo. We also observed that
      U18666A, an inducer of cholesterol accumulation, increased inducible NOS
      expression, JNK activation, and DNA damage in the wild type (WT)-aNSCs.
      Interestingly, we found that endogenous cholesterol efflux transporters and their
      regulator were less activated in the SVZ than in the DG, in both WT and NPC mice.
      This result explains the high vulnerability of SVZ-derived aNSCs to the
      cholesterol imbalance as observed in NPC mice. Innovation and Conclusion: In this
      study, we demonstrated that the SVZ-derived aNSCs might be major targets of NPC.
      Significantly, aNSCs showed different responses depending on their anatomical
      origins due to dissimilarities in their cholesterol transporting system and NO
      dependent JNK activation. These findings can contribute to the understanding of
      the region-specific nature of the two SVZ and DG neurogenic niches. Antioxid.
      Redox Signal. 00, 000-000.

PMID- 22384815
TI  - Effects of sleep position on time course in remission of positional vertigo in
      patients with benign paroxysmal positional vertigo.
AB  - CONCLUSION: The findings suggest that it is easy for otoconial debris dislodged
      from the utricle to fall into the posterior semicircular canal (PSCC) or the
      horizontal semicircular canal (HSCC) of the undermost ear during sleep, but not
      to exit from the uppermost ear in patients with benign paroxysmal positional
      vertigo (BPPV). OBJECTIVE: The aims of the present study were two-fold. (1) To
      examine the association between the preferred side of head-lying during sleep and
      the side of the affected ear in patients with both posterior canal BPPV (P-BPPV)
      and horizontal canal BPPV (H-BPPV). (2) To see whether that position affects the
      time course in remission of their positional vertigo. METHODS: One hundred and
      sixteen patients with P-BPPV and 40 patients with H-BPPV who showed a habitual
      preference for right or left side sleeping position were included in this study.
      RESULTS: The side of the affected ear was significantly associated with the head
      lying side during sleep in patients with P-BPPV and was closely but not
      significantly associated with it in patients with H-BPPV. However, the head-lying
      side during sleep did not affect the remission rate of their positional vertigo.

PMID- 22384816
TI  - Limitations of the fetal anatomic survey via ultrasound in the obese obstetrical
      population.
AB  - OBJECTIVE: To evaluate limitations of the fetal anatomic survey in obese women.
      METHODS: Retrospective cohort study of obese gravidas with singleton gestations
      who had at least one, sonographic fetal evaluation at >= 14 weeks between January
      2009 and March 2011. The impact of pre-pregnancy body mass index (BMI), placental
      location, prior cesarean scar and sonographer experience on ability to achieve an
      adequate ultrasound was evaluated using multilevel modeling. Ability to visualize
      specific fetal parts by BMI class and gestational age was also evaluated.
      RESULTS: There were 245 obese women (42% with class III obesity). Senior faculty
      (>20 years experience) were more likely to achieve adequate visualization
      (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.15-9.25) compared
      with junior faculty. Among women with BMI > 40.0, odds of inadequate views of the
      face and spine were 10.0 (95% CI 1.31-76.0) and 5.17 (95% CI 0.65-40.8), when
      compared with women with a BMI = 30-34.9. Odds for inadequate views of sex (OR
      3.83; 95% CI 0.86-17.1) and extremities (OR 4.37; 95% CI 0.99-19.4) were
      similarly increased with a BMI >= 40. The optimal gestational age for a complete
      anatomic survey was 22-24 weeks (93% completion rate), with an OR of 41.3 (95% CI
      7.89-215.8), compared with a survey at 14-16 weeks. CONCLUSIONS: Attending
      sonographer experience is associated with improved visualization of fetal anatomy
      among obese gravidas. Face, spine, sex and extremity views are particularly
      difficult in the highest BMI category.

PMID- 22384817
TI  - Compound heterozygosity for Hb S [beta6(A3)Glu->Val] and Hb Kenya (Agamma81Leu
      beta86Ala) in a Ugandan woman.
AB  - Hb Kenya is a hemoglobin (Hb) tetramer composed of two normal alpha- and two non
      alpha-globin chains. The latter are the product of a fusion gene in which the 5'
      end is (A)gamma and the 3' end is beta. The crossover point is between codon 81
      of the (A)gamma gene and codon 86 of the beta gene. Like the other non alpha
      genes, the hybrid protein product ((A)gamma81Leu-beta86Ala) has 146 amino acids.
      The purpose of this report is to highlight the laboratory findings of Hb Kenya
      and to emphasize the pitfalls in misdiagnosis, particularly when associated with
      another variant such as Hb S [beta6(A3)Glu->Val].

PMID- 22384818
TI  - Symmetric halogen bonding is preferred in solution.
AB  - Halogen bonding is a recently rediscovered secondary interaction that shows
      potential to become a complementary molecular tool to hydrogen bonding in
      rational drug design and in material sciences. Whereas hydrogen bond symmetry has
      been the subject of systematic studies for decades, the understanding of the
      analogous three-center halogen bonds is yet in its infancy. The isotopic
      perturbation of equilibrium (IPE) technique with (13)C NMR detection was applied
      to regioselectively deuterated pyridine complexes to investigate the symmetry of
      [N-I-N](+) and [N-Br-N](+) halogen bonding in solution. Preference for a
      symmetric arrangement was observed for both a freely adjustable and for a
      conformationally restricted [N-X-N](+) model system, as also confirmed by
      computation on the DFT level. A closely attached counterion is shown to be
      compatible with the preferred symmetric arrangement. The experimental
      observations and computational predictions reveal a high energetic gain upon
      formation of symmetric, three-center four-electron halogen bonding. Whereas
      hydrogen bonds are generally asymmetric in solution and symmetric in the
      crystalline state, the analogous bromine and iodine centered halogen bonds prefer
      symmetric arrangement in solution.

PMID- 22384819
TI  - The Telephone Interview for Cognitive Status (Modified): relation with a
      comprehensive neuropsychological assessment.
AB  - The modified Telephone Interview for Cognitive Status (TICS-m) is a widely used
      screening instrument for (Alzheimer's) dementia. Psychometric evaluation of the
      TICS-m is limited. This study examined the relation between the TICS-m and a
      comprehensive neuropsychological assessment in older persons (n = 243) without
      cognitive deficits. The TICS-m total score correlated with multiple cognitive
      domains (range r = .22-.49). Factor analysis of the TICS-m items yielded four
      interpretable factors: "verbal memory," "orientation/mental tracking,"
      "language/reasoning," and "attention/working memory," which also showed (modest)
      correlations with the neuropsychological assessment (r = .02-.48). The TICS-m
      appears to reflect a "general cognitive ability" rather than, for example, memory
      functioning alone.

PMID- 22384821
TI  - Pharmacometabonomic investigation of dynamic metabolic phenotypes associated with
      variability in response to galactosamine hepatotoxicity.
AB  - Galactosamine (galN) is widely used as an in vivo model of acute liver injury. We
      have applied an integrative approach, combining histopathology, clinical
      chemistry, cytokine analysis, and nuclear magnetic resonance (NMR) spectroscopic
      metabolic profiling of biofluids and tissues, to study variability in response to
      galactosamine following successive dosing. On re-challenge with galN, primary non
      responders displayed galN-induced hepatotoxicity (induced response), whereas
      primary responders exhibited a less marked response (adaptive response). A
      systems-level metabonomic approach enabled simultaneous characterization of the
      xenobiotic and endogenous metabolic perturbations associated with the different
      response phenotypes. Elevated serum cytokines were identified and correlated with
      hepatic metabolic profiles to further investigate the inflammatory response to
      galN. The presence of urinary N-acetylglucosamine (glcNAc) correlated with
      toxicological outcome and reflected the dynamic shift from a resistant to a
      sensitive phenotype (induced response). In addition, the urinary level of glcNAc
      and hepatic level of UDP-N-acetylhexosamines reflected an adaptive response to
      galN. The unique observation of galN-pyrazines and altered gut microbial
      metabolites in fecal profiles of non-responders suggested that gut microfloral
      metabolism was associated with toxic outcome. Pharmacometabonomic modeling of
      predose urinary and fecal NMR spectroscopic profiles revealed a diverse panel of
      metabolites that classified the dynamic shift between a resistant and sensitive
      phenotype. This integrative pharmacometabonomic approach has been demonstrated
      for a model toxin; however, it is equally applicable to xenobiotic interventions
      that are associated with wide variation in efficacy or toxicity and, in
      particular, for prediction of susceptibility to toxicity.

PMID- 22384820
TI  - Facile (triazolyl)methylation of MACOS-derived benzofused sultams utilizing ROMP
      derived OTP reagents.
AB  - A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates
      (OTP(n)) have been successfully utilized for the preparation of a 106-member
      library of triazole containing benzothiaoxazepine-1,1-dioxides. This report
      demonstrates the utilization of a suite of soluble OTP(n) reagents for facile
      (triazolyl)methylation of 10 MACOS-derived sultam scaffolds in purification-free
      process for parallel synthesis of small molecule collections for HTS.

PMID- 22384822
TI  - Supervising nursing students administering medication: a perspective from
      registered nurses.
AB  - AIMS: To explore the attitudes, experiences and opinions of registered nurses
      regarding supervision of undergraduate nursing students while administering
      medication in the healthcare setting. BACKGROUND: Medication errors present a
      considerable risk to safety in the healthcare setting. By virtue of their role in
      the administration of medication, registered nurses are considered as major
      contributors to this problem. Undergraduate nursing students administer
      medication in the clinical setting, but little attention has been paid to the
      implications for patient safety. DESIGN: This research was conducted using
      exploratory qualitative methodology. METHODS: Focus group interviews were
      conducted with 13 registered nurses. The participants were asked to describe
      their experiences and opinions regarding the supervision of undergraduate nursing
      students. Data were analysed using the framework approach. RESULTS: Three main
      themes from this work are presented in this paper: 'standard of supervision', 'a
      beneficial experience' and 'preparation'. CONCLUSIONS: The participants regarded
      supervision as an important process in fostering student learning and ensuring
      safety. Preparation on the part of the healthcare facility, students and the
      university were essential to maximise the benefits for all concerned. Relevance
      to clinical practice.  The ability to administer medication safely is an
      important skill for all registered nurses. Nursing students need the opportunity
      to develop these skills as part of their undergraduate educational programme.
      Registered nurses must supervise students in a rigorous and supportive manner to
      enhance learning and to promote quality care.

PMID- 22384823
TI  - High nuclear poly-(ADP-ribose)-polymerase expression is prognostic of improved
      survival in pancreatic cancer.
AB  - AIMS: Poly-(ADP-ribose)-polymerases (PARPs) act as post-translational modifiers
      of proteins that are mainly involved in the DNA repair machinery, and have
      recently been shown to be predictive of pathologically complete remission after
      chemotherapy in breast cancer. In the pancreas, PARP expression has so far only
      been studied in inflammatory conditions. Therefore, in this study, we
      investigated the relevance of PARP in pancreatic cancer. METHODS AND RESULTS:
      Cytoplasmic and nuclear PARP expression was assessed by immunohistochemistry in a
      population-based cohort of 178 adenocarcinomas of the pancreas and correlated
      with clinicopathological parameters. We found that low-level nuclear expression
      of PARP is associated with a poor prognosis (median survival 9.6 versus 14.5
      months, P = 0.004). CONCLUSIONS: Our analysis shows that nuclear PARP is an
      independent prognostic marker with respect to standard clinicopathological
      parameters. These results suggest that PARP should be further explored as a
      predictive factor with respect to conventional chemotherapy and concepts of PARP
      inhibitor therapy in pancreatic cancer.

PMID- 22384824
TI  - Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin
      in psoriatic skin lesions.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown
      aetiology, and an active form of vitamin D(3) (1alpha,25-dihydroxyvitamin D(3))
      and its analogues (VD3As) are widely used topical reagents for psoriasis
      treatment. Besides their well-known calcium homeostasis functions, VD3As have
      been shown to have various immune-modulating effects including the induction of
      thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2
      inflammation, in mouse models, but not yet in human psoriasis. VD3As also have
      been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of
      innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions;
      however, its role in this disease seems as yet inconclusive. OBJECTIVES: To
      clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the
      modulation of expression patterns of related cytokines in human psoriatic
      lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A
      treatment were subjected to immunohistochemical staining and quantitative reverse
      transcription-polymerase chain reaction analyses to measure the expression levels
      of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and
      activation-related chemokine and CCR4 expression were observed in VD3A+ skin
      samples than in VD3A- samples. In contrast, significantly lower levels of
      interleukin (IL)-12/23 p40, IL-1alpha, IL-1beta and tumour necrosis factor (TNF)
      alpha expression were observed in the VD3A+ samples than in the VD3A- samples.
      Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical
      VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression
      of IL-12/23 p40, IL-1alpha, IL-1beta and TNF-alpha, thereby ameliorating
      psoriatic plaques.

PMID- 22384825
TI  - Ethical professional practice: exploring the issues for health services to rural
      Aboriginal communities.
AB  - CONTEXT: This article provides a first person account of the experience of
      professional ethics for a psychologist who has worked in several Aboriginal
      communities in Alberta, Canada. ISSUES: These small rural communities tend to
      have few services and health services are typically provided by multidisciplinary
      health teams. Team members are predominantly community members, creating an
      embedded service environment that highlights the need for integrity in
      relationships. As the psychologist travelling to these communities I require
      sensitivity to cultural considerations, multiple party responsibilities, and
      community pressure on service delivery. LESSONS LEARNED: In these settings, in
      consideration of the principle of respect for the dignity of persons, there is
      enhanced need for non-discrimination, particularly as most community members are
      vulnerable persons. Also, the context of small community clinics highlights
      issues of privacy and confidentiality. Responsible caring in these kinds of
      general practice also raise ongoing questions about competence and the need for
      daily risk-benefit analysis. Finally, responsibility to society is also an
      overarching consideration given the conditions of Canadian Aboriginal
      communities.

PMID- 22384826
TI  - Swallowing function in Parkinson's patients following Zona Incerta deep brain
      stimulation.
AB  - OBJECTIVE: The purpose of the present study was to examine whether there was a
      negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on
      pharyngeal swallowing function in Parkinson's patients (PD). There are no former
      reports including swallowing and cZI DBS. METHODS: Eight patients (aged 49-71
      years; median 62) were evaluated pre- and post-operatively, at 6 and 12 months
      after DBS surgery. Evaluation tools were fiberoptic endoscopic evaluation of
      swallowing examinations and patients' self-assessments of their swallowing
      function including a visual analog scale and quality-of-life-related questions.
      The swallowing protocol included Rosenbek's Penetration-Aspiration Scale,
      Secretion Severity Scale and parameters for preswallow spillage, pharyngeal
      residue, and pharyngeal clearance. RESULTS: There was no clear-cut effect of
      neurostimulation post-operatively at 6 and 12 months on any of the swallowing
      parameters except for the preswallow spillage that was slightly worsened in the
      stimulation on condition 12 months post-operatively. The answers to the self
      assessment questions did not vary significantly. CONCLUSIONS: The effect of the
      stimulation on the swallowing function varied among individuals, but the overall
      outcome was that cZI DBS did not seem to have a negative influence on swallowing
      function in the eight patients studied.

PMID- 22384828
TI  - Fooled by local robustness.
AB  - One would have expected the considerable public debate created by Nassim Taleb's
      two best selling books on uncertainty, Fooled by Randomness and The Black Swan,
      to inspire greater caution to the fundamental difficulties posed by severe
      uncertainty. Yet, methodologies exhibiting an incautious approach to uncertainty
      have been proposed recently in a range of publications. So, the objective of this
      short note is to call attention to a prime example of an incautious approach to
      severe uncertainty that is manifested in the proposition to use the concept
      radius of stability as a measure of robustness against severe uncertainty. The
      central proposition of this approach, which is exemplified in info-gap decision
      theory, is this: use a simple radius of stability model to analyze and manage a
      severe uncertainty that is characterized by a vast uncertainty space, a poor
      point estimate, and a likelihood-free quantification of uncertainty. This short
      discussion serves then as a reminder that the generic radius of stability model
      is a model of local robustness. It is, therefore, utterly unsuitable for the
      treatment of severe uncertainty when the latter is characterized by a poor
      estimate of the parameter of interest, a vast uncertainty space, and a likelihood
      free quantification of uncertainty.

PMID- 22384827
TI  - The nature of innate and adaptive interleukin-17A responses in sham or bacterial
      inoculation.
AB  - Streptococcus pyogenes is the causative agent of numerous diseases ranging from
      benign infections (pharyngitis and impetigo) to severe infections associated with
      high mortality (necrotizing fasciitis and bacterial sepsis). As with other
      bacterial infections, there is considerable interest in characterizing the
      contribution of interleukin-17A (IL-17A) responses to protective immunity. We
      here show significant il17a up-regulation by quantitative real-time PCR in
      secondary lymphoid organs, correlating with increased protein levels in the serum
      within a short time of S. pyogenes infection. However, our data offer an
      important caveat to studies of IL-17A responsiveness following antigen
      inoculation, because enhanced levels of IL-17A were also detected in the serum of
      sham-infected mice, indicating that inoculation trauma alone can stimulate the
      production of this cytokine. This highlights the potency and speed of innate IL
      17A immune responses after inoculation and the importance of proper and
      appropriate controls in comparative analysis of immune responses observed during
      microbial infection.

PMID- 22384829
TI  - GSK3beta regulates gluconeogenic gene expression through HNF4alpha and FOXO1.
AB  - Hepatic gluconeogenesis is important for the maintenance of blood glucose
      homeostasis under fasting condition. Hepatocyte nuclear factor 4alpha (HNF4alpha)
      and FOXO1 transcription factors have implicated in this process through
      transcriptional regulation of glucose-6-phosphatase (G6Pase) and
      phosphoenolpyruvate carboxykinase (PEPCK), which are rate-limiting enzymes in
      gluconeogenesis. In this study, we demonstrate that glycogen synthase kinase
      3beta (GSK3beta) regulates the expression of gluconeogenic genes through
      HNF4alpha and FOXO1. Silencing of GSK3beta leads to reduction in the expression
      of gluconeogenic genes, including G6Pase, PEPCK, and peroxisome proliferator
      activated receptor gamma coactivator-1alpha. We show that GSK3beta directly binds
      to both HNF4alpha and FOXO1. Inhibition of GSK3 by SB-216763 abolishes HNF4alpha
      mediated activation of G6Pase promoter. We also found that overexpression of
      GSK3beta potentiates G6Pase promoter activation by FOXO1 in a manner dependent on
      its kinase activity. Treatment of SB-216763 diminishes FOXO1-mediated activation
      of G6Pase promoter. Taken together, these results reveal a previously
      unrecognized mechanism for the regulation of gluconeogenic gene expression.

PMID- 22384831
TI  - An evaluation of team and individual formularies to support independent
      prescribing in mental health care.
AB  - Mental health nurses have been entitled to train to become independent
      prescribers since May 2006; although the number of trained nurse prescribers
      seems to have increased steadily, a significant number of them have not actually
      undertaken prescribing roles on completion of their training or have limited
      their practice to supplementary prescribing. In order to support existing
      independent prescribers and to assist those nurses who have trained but are yet
      to prescribe independently, a mental health trust has piloted the use of
      individual and team formularies. An evaluation of this project indicated that
      formularies were well received by existing independent prescribers and were seen
      as a helpful instrument to support newly qualified and supplementary prescribers
      in their bid to become independent. Formularies can clarify and formalize each
      prescriber's area of competence, thus setting clear boundaries, reducing
      uncertainty and enhancing prescribers' confidence and willingness to take on this
      new role. Formularies may also be used to enhance communication with service
      users and further develop shared decision making. Effective procedures need to be
      in place to ensure formularies are up to date and reflect local practice.

PMID- 22384830
TI  - Vitrification with DAP 213 and cryotop of ex situ and in situ feline cumulus
      oocyte complexes.
AB  - This study was undertaken to compare cryotolerance, in terms of viability and
      resumption of meiosis after warming and culture (24 and 48 h), of ex situ
      (isolated) and in situ (enclosed in the ovarian tissue) feline cumulus-oocyte
      complexes (COCs) vitrified with DAP 213 (2 m DMSO, 1 m acetamide, 3 m propylene
      glycol) in cryotubes or Cryotop method. Ovaries were harvested from 49 pubertal
      queens. Of each pair of ovaries, one was dissected to release COCs randomly
      divided into three groups: fresh COCs (control), ex situ COCs vitrified with DAP
      213 and Cryotop. The cortex of the other ovary was sectioned into small fragments
      (approximately 1.5 mm(3)) and randomly assigned to be vitrified by DAP 213 or
      Cryotop. After warming, ex situ and in situ (retrieved form vitrified ovarian
      tissue) COCs were matured in vitro. Viability of oocytes was highly preserved
      after warming and culture in all treatments. Proportions of oocytes surrounded by
      complete layers of viable cumulus cells were remarkably decreased (p < 0.00001)
      in both vitrification procedures compared to fresh oocytes. Resumption of meiosis
      occurred in all treatments. After 24 h of culture, results were similar in ex
      situ and in situ vitrified oocytes regardless of the vitrification protocol used
      (range 29-40%), albeit lower (p < 0.05) than those of fresh oocytes (65.8%).
      After 48 h of culture, ex situ oocytes vitrified with Cryotop achieved the rates
      of meiosis resumption similar to fresh oocytes (53.8% vs 67.5%; p > 0.05) and ex
      situ and in situ oocytes vitrified with DAP 213 showed similar rates of
      resumption of meiosis. These findings demonstrated that DAP 213 and Cryotop
      preserve the viability of ex situ and in situ oocytes, but cumulus cells are
      highly susceptible to vitrification. However, the capability to resume meiosis
      evidences that feline immature oocytes vitrified as isolated or enclosed in the
      ovarian cortex have comparable cryotolerance.

PMID- 22384832
TI  - Comparison and analysis of theoretical models for diffusion-controlled
      dissolution.
AB  - Dissolution models require, at their core, an accurate diffusion model. The
      accuracy of the model for diffusion-dominated dissolution is particularly
      important with the trend toward micro- and nanoscale drug particles. Often such
      models are based on the concept of a "diffusion layer." Here a framework is
      developed for diffusion-dominated dissolution models, and we discuss the
      inadequacy of classical models that are based on an unphysical constant diffusion
      layer thickness assumption, or do not correctly modify dissolution rate due to
      "confinement effects": (1) the increase in bulk concentration from confinement of
      the dissolution process, (2) the modification of the flux model (the Sherwood
      number) by confinement. We derive the exact mathematical solution for a spherical
      particle in a confined fluid with impermeable boundaries. Using this solution, we
      analyze the accuracy of a time-dependent "infinite domain model" (IDM) and "quasi
      steady-state model" (QSM), both formally derived for infinite domains but which
      can be applied in approximate fashion to confined dissolution with proper
      adjustment of a concentration parameter. We show that dissolution rate is
      sensitive to the degree of confinement or, equivalently, to the total
      concentration C(tot). The most practical model, the QSM, is shown to be very
      accurate for most applications and, consequently, can be used with confidence in
      design-level dissolution models so long as confinement is accurately treated. The
      QSM predicts the ratio of diffusion layer thickness to particle radius (the
      Sherwood number) as a constant plus a correction that depends on the degree of
      confinement. The QSM also predicts that the time required for complete saturation
      or dissolution in diffusion-controlled dissolution experiments is singular (i.e.,
      infinite) when total concentration equals the solubility. Using the QSM, we show
      that measured differences in dissolution rate in a diffusion-controlled
      dissolution experiment are a result of differences in the degree of confinement
      on the increase in bulk concentration independent of container geometry and
      polydisperse vs single particle dissolution. We conclude that the constant
      diffusion-layer thickness assumption is incorrect in principle and should be
      replaced by the QSM with accurate treatment of confinement in models of diffusion
      controlled dissolution.

PMID- 22384833
TI  - Recovery of the horizontal vestibulo-ocular reflex in motorized head impulse test
      is common after vestibular loss.
AB  - CONCLUSION: Decreased horizontal vestibulo-ocular reflex (VOR) gain measured with
      the motorized head impulse rotator usually recovers at least partially within a
      few months after sudden unilateral vestibular loss. In addition to traditional
      evaluation of nystagmus, head impulse test responses provide valuable information
      on the severity and recovery of vestibular loss. OBJECTIVES: To quantify recovery
      of vestibular function with the motorized head impulse test in patients with
      acute unilateral peripheral vestibular loss, and to compare these results with
      other signs and symptoms. METHODS: We recorded prospectively the horizontal VOR
      with the motorized head impulse rotator in 30 patients with sudden unilateral
      vestibular deficit on average 3 days after the onset (early). Twenty patients
      were measured sequentially on average 3 months later (late). We calculated VOR
      gain and asymmetry (mean +/- standard deviation). RESULTS: The early ipsilesional
      gain of 0.49 +/- 0.21 improved highly significantly to the late gain of 0.79 +/-
      0.23 (p = 0.0000). The respective asymmetry improved highly significantly from 32
      +/- 18% to 12 +/- 14% (p = 0.0002). Gain or asymmetry recovered at least
      partially in 80% of the patients. The late high symptom score correlated with low
      gain (p = 0.043) and high asymmetry (p = 0.018).

PMID- 22384835
TI  - Frailty and dementia: common but complex comorbidities.

PMID- 22384836
TI  - Iridium-catalyzed C-H borylation-based synthesis of natural indolequinones.
AB  - An iridium-catalyzed C-H borylation provides the key step in a short synthesis of
      two indolequinone natural products. This regioselective C-H functionalization
      strategy delivers 7-borylindoles that undergo facile oxidation-hydrolysis to 7
      hydroxyindoles and subsequent oxidation to the desired indolequinones, thereby
      demonstrating a powerful application of the iridium-catalyzed C-H borylation
      reaction. A significant result has arisen from the iridium-catalyzed borylation
      of N-diethylhydrosilyl-6-methoxyindole; even in the presence of a substituent at
      C6, the N-hydrosilyl group still directs borylation exclusively into the more
      sterically hindered C7 position in preference to C2.

PMID- 22384837
TI  - Continuous glucose monitoring and insulin pump therapy for diabetes in pregnancy.
AB  - Continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin
      infusion (CSII) systems, or insulin pumps, offer great promise for improved
      glycemic control during pregnancy. Combined, these two devices could potentially
      constitute an artificial pancreas, where real-time blood glucose readings are
      relayed to an insulin pump that uses a personalized algorithm to decide how much
      insulin is needed by the patient's body. However, the promise of these two
      systems have not yet been proven individually or in combination in controlled
      clinical trials to improve pregnancy outcomes. Such trials are urgently needed
      before the widespread use of these devices in pregnancy can be justified.

PMID- 22384838
TI  - Nondeletional Hb Queens Park [alpha32(B13)Met->Lys]/Hb H (beta4) disease.
AB  - A rare nondeletional alpha-thalassemia-2 (alpha-thal-2) allele was identified in
      a Thai boy with Hb H (beta4) disease. The proband has alpha-thal-1 (- -(SEA)
      type) together with a non productive Hb Queens Park (HBA1:c.98T>A)
      [alpha32(B13)Met->Lys] alpha1-globin variant. No abnormal hemoglobin (Hb)
      fraction was detected by high performance liquid chromatography (HPLC). The
      clinical effect of this mutation in the proband was comparable to that of
      deletional alpha-thal-2 present in Hb H disease.

PMID- 22384839
TI  - The role of bacterial vaginosis and trichomonas in HIV transmission across the
      female genital tract.
AB  - Bacterial vaginosis (BV) and Trichomonas vaginalis (TV) infections are both very
      common and are associated with increased risk of sexual transmission of HIV.
      There are several mechanisms by which BV and TV could affect susceptibility
      including inducing pro-inflammatory cytokines and disrupting mucosal barrier
      function. This review highlights recent advances in our understanding of how
      these genital conditions lead to an increased risk of HIV infection in women.

PMID- 22384840
TI  - Modulation of HIV transmission by Neisseria gonorrhoeae: molecular and
      immunological aspects.
AB  - Neisseria gonorrhoeae (GC), a major cause of pelvic inflammatory disease, can
      facilitate HIV transmission. In response to GC infection, genital epithelial
      cells can produce cytokines, chemokines and defensins to modulate HIV infection
      and infectivity. GC can also induce the production of cytokines and chemokines in
      monocytes and modulate T cell activation. In vivo, an increase in the number of
      endocervical CD4+ T cells has been found in GC-infected women. Additionally, GC
      appears to modulate HIV-specific immune responses in HIV-exposed sex workers.
      Interestingly, in vitro, GC exhibits HIV enhancing or inhibitory effects
      depending on the HIV target cells. This review summarizes molecular and
      immunological aspects of the modulation of HIV infection and transmission by GC.
      Future studies using a multi-cellular system or in animal models will offer
      insight into the mechanisms by which GC increases HIV transmission.

PMID- 22384843
TI  - Microbial interaction of periodontopathic bacterium Porphyromonas gingivalis and
      HIV-possible causal link of periodontal diseases to AIDS progression-.
AB  - A wide variety of infections, including bacteria, viruses, fungi and protozoa
      occur in the immunocompromised condition associated with human immunodeficiency
      virus type 1 (HIV-1) infection and acquired immunodeficiency syndrome (AIDS).
      Although these opportunistic infections are believed to arise as an effect of the
      immunodeficiency, these microbes sometimes promote the disease progression of HIV
      1 infection by enhancing viral replication or modulating host immune responses.
      Here we review the experimental and clinical evidence supporting such causal
      relationships associated with periodontogenic bacteria. Periodontal disease,
      caused by subgingival infection with oral anaerobic bacteria, typically
      Porphyromonas gingivalis (P. gingivalis) belonging to the phylum Bacteroidetes,
      is found worldwide and is one of the most prevalent microbial diseases of
      mankind. Emerging evidence implicates the involvement of P. gingivalis infection
      in the progression of HIV-1 infection. We demonstrate that P. gingivalis can
      induce HIV-1 reactivation via chromatin modification, and that the bacterial
      metabolite butyric acid produced in anaerobic conditions is responsible for this
      effect. These findings suggest that periodontal diseases could act as a risk
      factor for HIV-1 reactivation in infected individuals and might contribute to
      AIDS progression. Furthermore, it would imply that prevention and early treatment
      of periodontitis involving P. gingivalis infection could effectively block
      further clinical progression of AIDS.

PMID- 22384844
TI  - The anemia prevalence and the association between complete blood count analysis
      and renal function parameters in HIV-1-infected patients.
AB  - OBJECTIVES: To determine the anemia prevalence and the correlation between
      complete blood count (CBC) analysis and renal function parameters in HIV-1
      infected population. METHODS: It was a single-center study set in Warsaw (Poland)
      over a 3-year period. The study was performed in 214 adult HIV-1- infected
      patients (180 males and 34 females, aged from 20 to 69 years old, mean age 39.55
      years, 130 on combined antiretroviral therapy, cART). Glomerular filtration rate
      (GFR) was estimated using the re-expressed Modification of Diet in Renal Disease
      (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      formulas. In statistical analyses U Mann-Whitney and Spearman correlation test as
      logistic regression analysis was used. RESULTS: 25.2% of studied patients were
      anemic. In all of them, estimated GFR (eGFR) was positively correlated with red
      blood cells (RBC) and platelet (PLT) count, and negatively correlated with mean
      corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC).
      All these correlations were statistically significant (p < 0.001) and independent
      of gender and used type of eGFR formula. In logistic regression analysis, lower
      eGFR strongly predicted lower RBC and PLT levels (p < 0.0001; OR 0.08, 95%CI:
      0.03, 0.22 and OR 0.99, 95%CI: 0.987, 0.993, respectively). CONCLUSIONS: Our
      findings suggest a strong association between CBC and renal function in ARV
      treated HIV-infected patients who fulfilled the criteria of anemia. Consequently,
      eGFR in all HIV-infected subjects with anemia, especially on treatment with
      nephrotoxic drugs and concomitant thrombocytopenia, should be monitored more
      frequently then standardly recommended every 3-6 months.

PMID- 22384841
TI  - Potential mechanisms for increased HIV-1 transmission across the endocervical
      epithelium during C. trachomatis infection.
AB  - Among the now pandemic sexually transmitted infections (STIs), Chlamydia
      trachomatis (C. trachomatis) is the predominant bacterial pathogen and human
      immunodeficiency virus type 1 (HIV-1) is the most lethal of the viral pathogens.
      The female genital tract is the primary site for heterosexual transmission of
      both C. trachomatis and HIV-1. Infection with C. trachomatis, and with a variety
      of other STIs, increases the risk for transmission of HIV-1, although the
      mechanisms for this finding remain unclear. We have used in vitro modeling to
      assess the mechanisms by which infection with genital C. trachomatis serovars
      might increase the transmission of HIV-1 across the female genital tract. C.
      trachomatis infection of an immortalized endocervical epithelial cell line (A2EN)
      increases the cell surface expression of the HIV-1 alternative primary receptor,
      galactosyl ceramide (GalCer), and of the HIV-1 co-receptors, CXCR4 and CCR5. C.
      trachomatis infection also increases the binding of HIV-1 to A2EN cells, and,
      subsequently, increases levels of virus in co-cultures of HIV-exposed A2EN and
      susceptible MT4-R5 T cells. Finally, in vivo endocervical cell sampling reveals a
      dramatic increase in the number of CD4+, CXCR4 and/or CCR5 positive T cell
      targets in the endocervix of C. trachomatis positive women when compared to those
      who are C. trachomatis negative. This combination of in vitro and in vivo results
      suggests several mechanisms for increased transmission of HIV-1 across the
      endocervices of C. trachomatis-infected women.

PMID- 22384842
TI  - Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV
      1: new insights and interventions.
AB  - Over the last thirty years, epidemiologic and molecular studies indicate a strong
      and synergist relationship between the dual epidemics of herpes simplex type 2
      (HSV-2) and HIV-1 infection. While prospective studies show that HSV-2 infection
      increases the risk for HIV-1 acquisition by 2- to 3-fold, HSV-2 suppression with
      standard prophylactic doses of HSV-2 therapy did not prevent HIV-1 acquisition.
      Reconciling these discrepancies requires understanding recent HSV-2 pathogenesis
      research, which indicates HSV-2 infection is not a latent infection with
      infrequent recurrence but a near constant state of reactivation and viral
      shedding which is not completely suppressed by standard antivirals. Because
      current antivirals do not prevent or fully suppress HSV-2 replication, priorities
      are HSV-2 vaccine development and antivirals that reach high concentrations in
      the genital mucosa and suppress the persistent genital inflammation associated
      with genital herpes reactivation in order to reduce the increased susceptibility
      to HIV-1 infection associated with HSV-2. HIV-1 and HSV-2 synergy is also seen
      among co-infected individuals who exhibit higher HIV-1 viral load compared to HSV
      2 uninfected individuals. Standard HSV-2 therapy modestly lowers HIV-1 viral load
      and is associated with slower HIV-1 disease progression. A promising area of
      research is higher doses of HSV-2 suppressive therapy achieving a greater
      reduction in plasma HIV-1 RNA, which could translate to greater reductions in HIV
      1 disease progression and infectiousness. However, many questions remain to be
      answered including potential effectiveness and cost-effectiveness of higher dose
      HSV-2 suppressive therapy. Mathematical models of HSV-2 and HIV-1 at a population
      level would be useful tools to estimate the potential impact and cost
      effectiveness of higher dose HSV-2 suppressive therapy.

PMID- 22384845
TI  - Risk factors for pneumococcal nasopharyngeal colonization before and after
      pneumococcal conjugate vaccination in persons with HIV: brief report.
AB  - HIV-infected individuals have excess rates of invasive pneumococcal disease. We
      investigated risk factors for nasopharyngeal pneumococcal colonization at
      baseline and after 9 months in 96 HIV patients immunized twice with 7- valent
      pneumococcal conjugate vaccine +/-1mg CPG 7909. In total, 22 patients (23%) were
      colonized, 11 at baseline only, four at both baseline and 9 months, and seven at
      9 months only. Compared to non-colonized patients, more colonized patients were
      smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization,
      antiretroviral treatment and the CPG adjuvant had no impact on colonization.
      These results suggest preventive strategies in addition to pneumococcal
      immunization.

PMID- 22384846
TI  - Online coupling of digital microfluidic devices with mass spectrometry detection
      using an eductor with electrospray ionization.
AB  - MS detection coupled with digital microfluidic (DMF) devices has most commonly
      been demonstrated in an offline manner using matrix assisted laser desorption
      ionization. In this work, an eductor is demonstrated which facilitated online
      coupling of DMF with electrospray ionization MS detection. The eductor consisted
      of a transfer capillary, a standard ESI needle, and a tapered gas nozzle. As a
      pulse of N(2) was applied to the nozzle, a pressure differential was induced at
      the outlet of the ESI needle that pulled droplets from the DMF, past the ESI
      needle, and into the flow of gas exiting the nozzle, allowing detection by MS.
      Operating position, ionization potential, and N(2) pressure were optimized, with
      the optimum ionization potential and N(2) pressure found to be 3206 V and 80 psi,
      respectively. Online MS detection was demonstrated from both open and closed DMF
      devices using 2.5 MUL and 630 nL aqueous droplets, respectively. Relative
      quantitation by DMF-MS was demonstrated by mixing droplets of caffeine with
      droplets of theophylline on an open DMF device and comparing the peak area ratio
      obtained to an on-chip generated calibration curve. This eductor-based method for
      transferring droplets has the potential for rapid, versatile, and high-throughput
      microfluidic analyses.

PMID- 22384849
TI  - Socialisation of new graduate nurses to practising nurses.
AB  - AIMS: The aim of this study was to explore the socialisation experiences of new
      graduate baccalaureate nurses to practising nurses. BACKGROUND: How nurses
      contend with the stress of their professional role has been of interest to both
      researchers and healthcare administrators over the past 30 years. Work stress of
      clinical nurses comes mainly from organisational and professional factors.
      However, few studies have explored the professional and organisational
      socialisation experiences of new graduate nurses. DESIGN: A qualitative
      descriptive approach was adopted. METHODS: Participants were graduates of a
      baccalaureate nursing programme and employed full time at four medical centres in
      Taiwan, their first full-time work experience. Data were collected through semi
      structured, open-ended, in-depth interviews, which were transcribed verbatim and
      analysed by content analysis. Three themes were identified: overwhelming chaos,
      learning by doing and being an insider. RESULTS: Although the professional
      socialisation process was hard for the new graduate nurses, they needed much time
      to increase their knowledge and clinical skills to fulfil clinical needs.
      However, the hardest work was the organisational socialisation process, which
      involved fitting into the bureaucratic system, such as maintaining interpersonal
      relationships with colleagues and familiarising themselves with the ward rules
      and culture. Neophyte nurse participants were also frustrated by the conflict
      between professional and organisational values. CONCLUSIONS: The study findings
      show that the transition from new graduate nurse to practising nurse was
      stressful for these participants, particularly due to the clash between the
      professional value of patient-oriented nursing care and the organisational value
      of task-oriented nursing. RELEVANCE TO CLINICAL PRACTICE: Senior clinical nurses
      can consider this study's descriptions of new graduate nurses' experiences to
      help them become insiders and provide quality care.

PMID- 22384850
TI  - Drug trapping and delivery for Alzheimer's diagnosis.
AB  - In this investigation, a new design based on a PANDA ring resonator as an optical
      trapping tool for tangle protein, molecular motor storage, and delivery is
      proposed. The optical vortices are generated and the trapping mechanism is
      controlled in the same way as the conventional optical tweezers. The trapping
      force is produced by a combination of the gradient field and scattering photons.
      The required molecular volume is trapped and moved dynamically within the
      molecular network. The tangle protein and molecular motor can be transported and
      delivered to the required destinations for Alzheimer's diagnosis by molecular
      buffer and bus network.

PMID- 22384851
TI  - Immobilization of paraoxonase onto chitosan and its characterization.
AB  - Paraoxonase was covalently immobilized onto a glutaraldehyde containing amino
      group functionalized chitosan surface by chemical immobilization at pH 8.0. The
      amount of covalently bound hPON1 was found to be 32 mg/10 chitosan beads. The
      properties of immobilized enzyme were investigated and compared to those of free
      enzyme. The effects of various parameters such as pH, temperature, heat, and
      storage stability on immobilized enzyme were investigated. Kinetic parameters of
      the immobilized enzyme were also evaluated. Thermal and storage stability
      experiments were carried out. It was observed that the immobilized enzyme had
      longer storage stability and retained 50 % of its initial activity during 26
      days.

PMID- 22384852
TI  - Characteristics of peripheral nerve regeneration following a second nerve injury
      and repair.
AB  - During the process of peripheral nerve regeneration, a single neuron can
      regenerate and maintain more than one collateral in a regenerative distal stump.
      Furthermore, some of the new shoots can mature gradually through remyelination
      and grow into the remote target organ to play a physiological function. Our study
      found that when neonatal nerve fibers are subjected to a second injury, the
      regenerative distal stump can regenerate and maintain more than one collateral in
      the second regenerative distal stump. The neonatal nerve contributed to the
      functional recovery of the nerve, but the restoration of nerve function was not
      complete.

PMID- 22384853
TI  - Implanted electro-acupuncture electric stimulation improves outcome of stem
      cells' transplantation in spinal cord injury.
AB  - Spinal cord injury (SCI) is one of the most serious disorders in clinics, and the
      high disability rate and functional deficits are common issues in patients.
      Transplantation of bone-marrow-derived mesenchymal stromal cells (BMSCs) into the
      injured spinal cord is emerging as a novel method in the therapeutics of SCI;
      however, its application is limited by the poor survival rate of the transplanted
      cells and low differentiation rate into neurons. Our laboratory recently reported
      that electrical stimulation (ES) dramatically improves the survival rate of
      transplanted BMSCs and increases spinal cord functions in animals with spinal
      cord injury. In this paper, we asked whether implanted electro-acupuncture (iEA)
      can advance the beneficial effects from the ES treatment in animals with spinal
      cord injury. We showed that BMSCs transplantation alone resulted in significant
      functional recovery in animals. Interestingly, iEA with BMSCs treatment induced a
      significantly higher functional improvement in locomotor functions and SSEP
      compared to the BMSCs treatment alone. Additionally, we used molecular biology
      techniques and showed that BMSCs transplantation with iEA treatment significantly
      increased the number of surviving BMSCs compared to the BMSCs alone group. In
      conclusion, our experiment showed that the approach of coupling iEA electric
      stimulation and BMSCs transplantation remarkably promotes functional improvements
      in animals with spinal cord injury and holds promising potential to treat spinal
      cord injury in humans.

PMID- 22384854
TI  - Executive function outcomes of children with traumatic brain injury sustained
      before three years.
AB  - Traumatic brain injury (TBI) is a common cause of disability in childhood. While
      the outcomes of TBI sustained in school years has been heavily researched, very
      little is known about the impact of TBI in infants and young children. The aim of
      this study was to investigate the impact of TBI on executive function (EF) in
      children who sustained a TBI before 3 years of age. A group of 55 children, 19
      with a mild TBI, 16 children with a moderate-severe TBI, and 20 uninjured
      comparison children participated. The EF of children aged 3 to 6 years were
      compared using child-based measures of attentional control and information
      processing. Parents completed questionnaires rating their child's EF. Severity
      groups differed on the child-based EF measure of attentional control with
      children with TBI performing below the control group. There were no significant
      group differences for information processing or parent-rated EF. It appears that
      children who sustain a TBI before the age of 3 years display impairments in some
      areas of attentional control 3-4 years postinjury. The findings fit with the
      existing EF literature for older children.

PMID- 22384855
TI  - Understanding the process of patient satisfaction with nurse-led chronic disease
      management in general practice.
AB  - AIMS:   To investigate the process of patient satisfaction with nurse-led chronic
      disease management in Australian general practice. BACKGROUND:   Nurses working
      in the primary care context of general practice, referred to as practice nurses,
      are expanding their role in chronic disease management; this is relatively new to
      Australia. Therefore, determining patient satisfaction with this trend is
      pragmatically and ethically important. However, the concept of patient
      satisfaction is not well understood particularly in relation to care provided by
      practice nurses. DESIGN:   A grounded theory study underpinned by a relativist
      ontological position and a relativist epistemology. METHODS:   Grounded theory
      was used to develop a theory from data collected through in-depth interviews with
      38 participants between November 2007-April 2009. Participants were drawn from a
      larger project that trialled a practice nurse-led, collaborative model of chronic
      disease management in three Australian general practices. Theoretical sampling,
      data collection, and analysis were conducted concurrently consistent with
      grounded theory methods. RESULTS:   Patients undergo a cyclical process of
      Navigating Care involving three stages, Determining Care Needs, Forming
      Relationship, and Having Confidence. The latter two processes are inter-related
      and a feedback loop from them informs subsequent cycles of Determining Care
      Needs. If any of these steps fails to develop adequately, patients are likely to
      opt out of nurse-led care. CONCLUSION:   Navigating Care explains how and why
      time, communication, continuity, and trust in general practitioners and nurses
      are important to patient satisfaction. It can be used in identifying suitable
      patients for practice nurse-led care and to inform the practice and organization
      of practice nurse-led care to enhance patient satisfaction.

PMID- 22384856
TI  - Core dysfunction in schizophrenia: electrophysiology trait biomarkers.
AB  - OBJECTIVE: Core symptoms of schizophrenia, particularly in the cognitive domain
      are hypothesized to be due to an abnormality in neural connectivity. Biomarkers
      of connectivity may therefore be a promising tool in exploring the aetiology of
      schizophrenia. We used electrophysiological methods to demonstrate abnormal
      visual information processing during in patients performing a simple cognitive
      task. METHOD: Electrophysiological recordings were acquired from 20 chronically
      ill, medicated patients diagnosed with either schizophrenia or schizo-affective
      disorder and 20 healthy volunteers while they conducted a working memory (WM)
      task. RESULTS: The patient group had significantly lower accuracy on the WM task
      and a trend for slower responses. An early visual evoked response potential was
      reduced in patients. Analysis of the electroencephalographic oscillations showed
      a decreased phase-locking factor (in the theta, beta and gamma bands) and signal
      power (theta frequency band). The beta and gamma oscillatory abnormalities were
      confined to two sets of correlated fronto and occipital electrodes. CONCLUSION:
      The findings of event-related potential and oscillatory abnormalities in patients
      with schizophrenia confirm the sensitivity of early visual information processing
      measurements for identification of schizophrenia phenotype. The fronto-occipital
      distribution of the oscillatory abnormalities replicates our findings from a
      schizotypal sample and implicates a possible top-down dysfunction as a
      vulnerability trait.

PMID- 22384857
TI  - The negotiation of the sick role: general practitioners' classification of
      patients with medically unexplained symptoms.
AB  - In encounters between general practitioners (GPs) and patients with medically
      unexplained symptoms (MUS), the negotiation of the sick role is a social process.
      In this process, GPs not only use traditional biomedical diagnostic tools but
      also rely on their own opinions and evaluations of a patient's particular
      circumstances in deciding whether that patient is legitimately sick. The doctor
      is thus a gatekeeper of legitimacy. This article presents results from a
      qualitative interview study conducted in Denmark with GPs concerning their
      approach to patients with MUS. We employ a symbolic interaction approach that
      pays special attention to the external validation of the sick role, making GPs'
      accounts of such patients particularly relevant. One of the article's main
      findings is that GPs' criteria for judging the legitimacy of claims by those
      patients that present with MUS are influenced by the extent to which GPs are able
      to constitute these patients as people with social problems and problematic
      personality traits.

PMID- 22384858
TI  - The tumour suppressor p53 is frequently nonfunctional in Sezary syndrome.
AB  - BACKGROUND: Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group
      with Sezary syndrome (SS) as one of the most aggressive variants. Recently, we
      identified a loss of E2A as a recurrent event in SS, which enhanced proliferation
      via upregulation of the proto-oncogene MYC. MYC-induced transformation usually
      requires deleterious alterations of key apoptotic genes including p53; however,
      p53 functionality and mutation status in SS are unclear. OBJECTIVES: We
      investigated functionality of p53 signalling by pharmacological treatment with
      the MDM2 antagonist nutlin-3, which might result in p53 activation. Furthermore,
      we analysed the TP53 mutation status in CTCL cell lines and highly purified
      tumour cells from patients with SS by mRNA and DNA sequencing. METHODS: We
      analysed the apoptosis induction due to nutlin-3 treatment in various SS cell
      lines and primary patient samples by annexin V/propidium iodide staining.
      Induction of p53 target genes was analysed by immunoblotting, and TP53 was
      sequenced at the mRNA and DNA level. RESULTS: We identified various TP53
      mutations and an impaired p53 signalling in the vast majority of the investigated
      cell lines and primary SS cells. CONCLUSIONS: In accordance with the importance
      of MYC deregulation in SS, p53 signalling is frequently nonfunctional in SS.
      However, although most likely ineffective as exclusive treatment in SS, it
      remains possible that pharmacological p53 activation could be beneficial in
      combination with other approaches including classical chemotherapeutics.

PMID- 22384860
TI  - Daily inhalation rate and time-activity/location pattern in Japanese preschool
      children.
AB  - Lack of data on daily inhalation rate and activity of children has been an issue
      in health risk assessment of air pollutants. This study aimed to obtain the daily
      inhalation rate and intensity and frequency of physical activity in relation to
      the environment in Japanese preschool children. Children aged four-six years (n=
      138) in the suburbs of Tokyo participated in this study, which involved three
      days' continuous monitoring of physical activity using a tri-axial accelerometer
      and parent's completion of a time/location diary during daily life. The estimated
      three-day mean daily inhalation rate (body temperature, pressure, saturated with
      water vapor) was 9.9 +/- 1.6 m(3) /day (0.52 +/- 0.09 m(3) /kg/day). The current
      daily inhalation rate value of 0.580 m(3) /kg/day proposed for use in health risk
      assessment in Japan is confirmed to be valid to calculate central value of
      inhaled dose of air pollutants in five- to six-year-old children. However, the
      95th percentile daily inhalation rate of 0.83 m(3) /kg/day based on measurement
      for five-year-old children is recommended to be used to provide an upper bound
      estimate of exposure that ensure the protection of all five- to six-year-old
      children from the health risk of air pollutants. Children spent the majority of
      their time in sedentary and light level of physical activity (LPA) when indoors,
      while 85% of their time when outdoors was spent in LPA and moderate-to-vigorous
      physical activity. The results suggest the need to consider variability of minute
      respiratory ventilation rate according to the environment for more refined short
      term health risk assessment.

PMID- 22384859
TI  - Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in
      humanized BLT NSG mice.
AB  - Dengue is a mosquito-borne viral disease of humans, and animal models that
      recapitulate human immune responses or dengue pathogenesis are needed to
      understand the pathogenesis of the disease. We recently described an animal model
      for dengue virus (DENV) infection using humanized NOD-scid IL2rgamma(null)  mice
      (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further
      improve this model by co-transplantation of human fetal thymus and liver tissues
      into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the
      sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell
      engrafted NSG mice. Furthermore, B cells generated during the acute phase and in
      memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM
      antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice
      secreted interferon-gamma in response to overlapping DENV peptide pools and HLA
      A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune
      responses to DENV vaccines and the effects of previous immunity on subsequent
      DENV infections.

PMID- 22384861
TI  - Atropisomers of hindered triarylisocyanurates: structure, conformation,
      stereodynamics, and absolute configuration.
AB  - The syn and anti diastereoisomers of some 1,3,5-triarylisocyanurate derivatives
      were isolated and their configuration assigned by NOE experiments and by X-ray
      diffraction. The kinetics of the syn/anti interconversion were determined, and
      the experimental activation energies matched satisfactorily the values predicted
      by DFT computations. Low-temperature NMR spectra were employed to determine the
      rotation barrier of N-bonded unhindered aryl substituents: these barriers, too,
      are satisfactorily reproduced by DFT computations. In the case of racemic
      diastereoisomers, the two expected enantiomers (atropisomers) were isolated by
      enantioselective HPLC and the absolute configuration established by DFT
      simulation of the electronic and vibrational circular dichroism spectra.

PMID- 22384862
TI  - How effective is high-support community-based step-down housing for women in
      secure mental health care? A quasi-experimental pilot study.
AB  - In the past decade UK government policy has been to develop alternative care for
      women detained in secure psychiatric hospital. This study evaluated the relative
      benefits of community-based step-down housing. Comparisons were made between
      female patients in community step-down housing and a control group in secure
      hospital who were on the waiting list for the houses. For each woman in the
      sample, a range of assessments was conducted on three separate occasions over a
      12-month period. We noted a gradual improvement over time in women in both
      settings. However, by the final assessment psychological well-being and security
      needs were significantly better in the community group (P < 0.05). Although risks
      for violence and social functioning were also somewhat better in this group
      throughout the study, no statistically significant differences between the groups
      were found in these areas at any assessment time. This study has generated
      evidence in support of the further development of high-support step-down
      community housing for women in secure psychiatric care. This initiative may
      provide greater personal freedom and enhanced relational security for the women
      concerned while also facilitating improvements in their psychological well-being,
      with no increased risk to the women themselves or to the wider community.

PMID- 22384863
TI  - Factors influencing patients with stage 5 chronic kidney disease to opt for
      conservative management: a practitioner research study.
AB  - AIMS AND OBJECTIVES: This study explored decision-making experiences of patients
      with stage 5 chronic kidney disease when opting for conservative management of
      their renal failure. BACKGROUND: Dialysis is an invasive treatment, and for some
      older patients, there is an associated treatment burden of dialysis-related
      symptoms. An alternative choice is conservative management, but little is known
      about those who make this decision and how they are supported through the
      process. DESIGN: Qualitative practitioner research study. METHOD: Data were
      generated from nine patients' naturally occurring clinic consultations with a
      renal clinical nurse specialist between May 2010 - July 2010. Interviews were
      transcribed verbatim and findings fed back at three multi-disciplinary meetings
      to check for relevance and resonance. Common themes were identified and codes
      applied. RESULTS: Patients reported age and having to travel three times a week
      to hospital for dialysis as reasons not to opt for treatment. Others felt well
      without dialysis not wanting to upset the 'status quo' or to burden loved ones.
      Most felt equipped to make the decision following explanation and discussion with
      the clinical nurse specialist in the renal clinic. CONCLUSIONS: Patients opting
      for conservative management give numerous reasons for this including old age,
      travel limitations, feeling well without dialysis and not wanting to be a burden,
      but appear content with their decision. One-to-one discussions with the clinical
      nurse specialist appear helpful during the decision-making process presenting an
      opportunity for advancing nursing roles in the chronic kidney disease service.
      RELEVANCE TO CLINICAL PRACTICE: Understanding patients' reasons for refusing
      dialysis assists in supporting until death. There is an opportunity for
      developing nursing practice to meet the multi-faceted needs of this group.

PMID- 22384864
TI  - Women's perceptions and experiences of group cognitive behaviour therapy and
      other group interventions for postnatal depression: a qualitative synthesis.
AB  - AIM: This paper is a report of a systematic review that aimed to synthesize
      qualitative evidence relating to women's perceptions and experiences of group
      cognitive behaviour therapy and other group interventions for postnatal
      depression. BACKGROUND: Postnatal depression may occur in women following
      childbirth, resulting in a range of distressing symptoms such as sadness,
      fatigue, and feelings of inability to look after their baby. Women tend to prefer
      psychological interventions. However, access to individual psychological therapy
      is limited by cost, waiting times, and availability of therapists. DATA SOURCES:
      A comprehensive literature search was conducted in 17 major psychological,
      medical, health-related and health economics electronic bibliographic databases.
      DESIGN: A qualitative evidence synthesis was conducted using thematic synthesis.
      REVIEW METHODS: Databases were searched from 1966-January 2008. A total of 116
      full papers were screened against the inclusion criteria. Included papers were
      quality assessed. The original review protocol was restricted to evidence on
      group cognitive behaviour therapy. However, due to the paucity of evidence, the
      inclusion criteria were broadened to include other group interventions. A
      thematic synthesis was undertaken of the data extracted from the included papers.
      RESULTS: Six studies were included. Specific benefits were that treatment enabled
      women to develop better relationships with their baby and understand postnatal
      depression. Negative aspects of treatment included difficulties in applying
      cognitive behavioural techniques, and unfavourable social comparisons with other
      group members. CONCLUSIONS: Women have contrasting perceptions and experiences of
      group treatment. This suggests that greater attention should be focused on
      identifying those most likely to benefit from these treatments in a group
      environment.

PMID- 22384865
TI  - Measuring glucose exposure and variability using continuous glucose monitoring in
      normal and abnormal glucose metabolism in pregnancy.
AB  - In pregnancy complicated by diabetes periods of hyperglycemia lead to accelerated
      fetal growth, resulting in a large for gestational age (LGA), or macrosomic,
      infant. Consequently, our aim was to measure the average volatility or
      variability in glucose control in women with and without diabetes in pregnancy.
      METHODS: Continuous glucose monitoring (CGM) was employed in 82 pregnant study
      subjects to collect and record unbiased self-monitored glucose values. We
      obtained results from 51 women with normal glucose tolerance in pregnancy (NGTP),
      25 gestational diabetes (GDM) and 6 women with pregestational diabetes (PreGD)
      between 18 and 45 (32 +/- 6) years of age. RESULTS: Significant differences (p <
      0.001) were found in glucose exposure between NGT and all but PreGD; whereas the
      percent of time in hypoglycemia was significantly (p < 0.0001) higher in all
      pregnancy groups when compared to the nonpregnant sample. We conclude that CGM
      confirmed that diurnal glucose patterns differ throughout the day by 20% when
      pregnant and nonpregnant states are compared. Indeed, maintenance of a narrow
      range in pregnancy is characteristic in women without diabetes, and CGM
      throughout pregnancy is critical, if mimicking normal glucose patterns is to be
      achieved.

PMID- 22384920
TI  - From a single whole exome read to notions of clinical screening: primary ciliary
      dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal
      recessive, causing early respiratory disease and later subfertility. Whole exome
      sequencing may enable efficient analysis for locus heterogeneous disorders such
      as PCD. We whole-exome-sequenced one consanguineous Saudi Arabian with clinically
      diagnosed PCD and normal laterality, to attempt ab initio molecular diagnosis. We
      reviewed 13 known PCD genes and potentially autozygous regions (extended
      homozygosity) for homozygous exon deletions, non-dbSNP codon, splice-site base
      variants or small indels. Homozygous non-dbSNP changes were also reviewed exome
      wide. One single molecular read representing RSPH9 p.Lys268del was observed, with
      no wild-type reads, and a notable deficiency of mapped reads at this location.
      Among all observations, RSPH9 was the strongest candidate for causality.
      Searching unmapped reads revealed seven more mutant reads. Direct assay for
      p.Lys268del (MboII digest) confirmed homozygosity in the affected individual,
      then confirmed homozygosity in three siblings with bronchiectasis. Our finding in
      southwest Saudi Arabia indicates that p.Lys268del, previously observed in two
      Bedouin families (Israel, UAE), is geographically widespread in the Arabian
      Peninsula. Analogous with cystic fibrosis CFTR p.Phe508del, screening for RSPH9
      p.Lys268del (which lacks sentinel dextrocardia) in those at risk would help in
      early diagnosis, tailored clinical management, genetic counselling and primary
      prevention.

PMID- 22384921
TI  - Identification of three novel Hb F variants: Hb F-Hayward [Ggamma1(NA1)Gly->Asp,
      GGT>GAT], Hb F-Chori-I [AgammaT16(A13)Gly->Asp, GGC>GAC] and Hb F-Chori-II
      [AgammaI29(B11)Gly->Glu, GGA>GAA].
AB  - Three new gamma-globin chain mutations were identified in four newborn samples
      referred to the Hemoglobinopathy Reference Laboratory at the Children's Hospital
      & Research Center Oakland, Oakland, CA, USA, for diagnostic testing. The variants
      were characterized by sequencing of amplified gamma-globin genes. These three
      novel variants have been named Hb F-Hayward [(G)gamma1(NA1)Gly->Asp, GGT>GAT], Hb
      F-Chori-I [(A)gamma(T)16(A13)Gly->Asp, GGC>GAC] and Hb F-Chori-II
      [(A)gamma(I)29(B11)Gly->Glu, GGA>GAA], respectively. No functional studies could
      be performed.

PMID- 22384922
TI  - Enhancement of amorphous celecoxib stability by mixing it with octaacetylmaltose:
      the molecular dynamics study.
AB  - In this paper, we present a novel way of stabilization of amorphous celecoxib
      (CEL) against recrystallization by preparing binary amorphous celecoxib
      octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As
      far as we know this is the first application of carbohydrate derivatives with
      acetate groups to enhance the stability of an amorphous drug. We found that CEL
      in the amorphous mixture with acMAL is characterized by a much better solubility
      than pure CEL. We report very promising results of the long-term measurements of
      stability of the CEL-acMAL binary amorphous system with small amount of
      stabilizer during its storage at room temperature. Moreover, we examined the
      effect of adding acMAL on molecular dynamics of CEL in the wide temperature range
      in both the supercooled liquid and glassy states. We found that the molecular
      mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much
      more limited than that in the case of pure CEL, which correlates with the better
      stability of the amorphous binary system. By dielectric measurements and
      theoretical calculations within the framework of density functional theory (DFT),
      we studied the role of acMAL in enhancing the stability of amorphous CEL in
      mixtures and postulated which interactions between CEL and acMAL molecules can be
      responsible for preventing devitrification.

PMID- 22384923
TI  - On the risk management and risk governance of petroleum operations in the Barents
      Sea area.
AB  - In this article, we discuss issues of risk management and risk governance with
      respect to petroleum operations in the Barents Sea area. We will focus on the
      decision problems related to whether or not to open the Barents Sea for petroleum
      activities in special vulnerable areas. We will explore to what extent the
      International Risk Governance Council risk governance framework provides valuable
      insights for and assistance to the decisionmaker and other stakeholders
      (including the industry and NGOs). The study covers issues related to risk
      assessment and appraisal, risk acceptance and tolerability, the use of the
      precautionary principle, risk perception, stakeholder involvement, risk
      communication, and risk management. The overall aim of the article is to point to
      areas where the risk governance could have been and can be improved for these and
      similar decision problems.

PMID- 22384924
TI  - Direct fitness of group living mammals varies with breeding strategy, climate and
      fitness estimates.
AB  - 1. Understanding how variation in fitness relates to variation in group living
      remains critical to determine whether this major aspect of social behaviour is
      currently adaptive. 2. Available evidence in social mammals aimed to examine this
      issue remains controversial. Studies show positive (i.e. potentially adaptive),
      neutral or even negative fitness effects of group living. 3. Attempts to explain
      this variation rely on intrinsic and extrinsic factors to social groups. Thus,
      relatively more positive fitness effects are predicted in singularly breeding as
      opposed to plural breeding species. Fitness effects of sociality in turn may
      depend on ecological conditions (i.e. extrinsic factors) that influence
      associated benefits and costs. 4. We used meta-analytic tools to review how
      breeding strategy or ecological conditions influence the effect size associated
      with direct fitness-sociality relationships reported in the mammalian literature.
      Additionally, we determined how taxonomic affiliation of species studied,
      different fitness and sociality measures used, and major climatic conditions of
      study sites explained any variation in direct fitness effect size. 5. We found
      group living had modest, yet positive effects on direct fitness. This generally
      adaptive scenario was contingent not only upon breeding strategy and climate of
      study sites, but also on fitness measures examined. Thus, positive and
      significant effects characterized singular as opposed to plural breeding
      strategies. 6. We found more positive fitness effects on studies conducted in
      tropical as opposed to temperate or arid climates. More positive and significant
      effects were noted on studies that relied on group fecundity, male fecundity and
      offspring survival as measures of fitness. 7. To conclude, direct fitness
      consequences of mammalian group living are driven by interspecific differences in
      breeding strategy and climate conditions. Other factors not examined in this
      study, namely individual variation in direct and indirect fitness benefits and
      potential interactions between social and ecological conditions, may be important
      and require further studies.

PMID- 22384925
TI  - Comparison of post-tonsillectomy pain with two different types of bipolar
      forceps: low temperature quantum molecular resonance device versus high
      temperature conventional electrocautery.
AB  - CONCLUSION: The low temperature device did not show any advantages over the
      conventional high temperature electrocautery in terms of the postoperative pain,
      operation time, and complications in pediatric tonsillectomy. OBJECTIVE: To
      compare post-tonsillectomy pain following the use of two different instruments
      with the same bipolar forceps techniques: low temperature quantum molecular
      resonance (QMR) device versus conventional high temperature electrocautery.
      METHODS: Pediatric patients admitted from July 2008 through January 2009 were
      included. The participants underwent bilateral tonsillectomy; one side by the QMR
      device and the other by the bipolar electrocautery. The sides for each instrument
      were counterbalanced by the order of presentation. The postoperative pain was
      measured using the faces pain rating scale. RESULTS: In all, 33 patients with a
      mean age of 7.6 years were enrolled. The postoperative pain, operation time, and
      complications in 33 sides dissected by the electrocautery and 33 sides by the QMR
      device were compared. The average operation times with each device were not
      statistically different. The mean ratings of the perception of pain related to
      each instrument were not different on operation day and postoperative day 1, day
      4, and day 7 (p = 0.133, 0.057, 0.625, and 1.0, respectively). There was no
      postoperative complication in any of the patients.

PMID- 22384926
TI  - Dye-loaded porous nanocapsules immobilized in a permeable polyvinyl alcohol
      matrix: a versatile optical sensor platform.
AB  - In this work we report on a versatile sensor platform based on encapsulated
      indicator dyes. Dyes are entrapped in hollow nanocapsules with nanometer-thin
      walls of controlled porosity. The porous nanocapsules retain molecules larger
      than the pore size but provide ultrafast access to their interior for molecules
      and ions smaller than the pore size. Dye-loaded nanocapsules are immobilized in a
      polyvinyl alcohol (PVA) matrix with high solvent permeability and rapid analyte
      diffusion. This approach provides robust sensing films with fast response and
      extended lifetime. To demonstrate the performance characteristics of such films,
      pH-sensitive indicator dyes were entrapped in vesicle-templated nanocapsules
      prepared by copolymerization of tert-butyl methacrylate, butyl methacrylate, and
      ethylene glycol dimethacrylate. As pH sensitive dyes, Nile blue A, bromophenol
      blue, and acid fuchsin were tested. Time-resolved absorbance measurements showed
      that the rate of the color change is controlled by the rate of diffusion of
      protons in the hydrogel. The pH-induced color change in a ~400 MUm thick film is
      complete within 40 and 60 s. The porous nanocapsule loaded films showed excellent
      stability and reproducibility in long-term monitoring experiments.
      Compartmentalization of the indicator dyes within the nanocapsules increased
      their stability. The matrix caused a shift in the position of the color change of
      the dye compared to that in an aqueous buffer solution. The
      encapsulation/immobilization protocol described in this account is expected to be
      broadly applicable to a variety of indicator dyes in optical sensor applications.

PMID- 22384927
TI  - LKB1 controls the pluripotent state of human embryonic stem cells.
AB  - Human embryonic stem cells maintained on human amniotic epithelial cells
      (hESCs(hAEC)) are better preserved in an undifferentiated state and express
      pluripotency genes Oct4, Nanog, and Sox2 at higher levels compared with growth on
      mitotically inactivated mouse embryonic fibroblasts (hESCs(MEF)). Here we report
      that this correlates with the absence of the tumor suppressor and metabolic
      balancer gene, LKB1 expression in hESCs(hAEC). RNA interference knockdown of LKB1
      in hESCs(MEF) resulted in upregulation of pluripotency marker genes of Oct4 and
      Nanog, while downregulation of differentiation markers (Runx1, AFP, GATA,
      Brachyury, Sox17 and Nestin). As in somatic cells, LKB1 controls p21/WAF1
      expression by promoter binding in hESCs(MEF). Our results suggested that the
      absence of LKB1-mediated signaling is an important determinant of feeder cell
      mediated support of hESC renewal.

PMID- 22384928
TI  - Feeder-free and serum-free production of hepatocytes, cholangiocytes, and their
      proliferating progenitors from human pluripotent stem cells: application to liver
      specific functional and cytotoxic assays.
AB  - We have established a serum- and feeder-free culture system for the efficient
      differentiation of multifunctional hepatocytes from human embryonic stem (ES)
      cells and three entirely different induced pluripotent stem (iPS) cells
      (including vector/transgene-free iPS cells generated using Sendai virus vector)
      without cell sorting and gene manipulation. The differentiation-inducing protocol
      consisted of a first stage; endoderm induction, second stage; hepatic initiation,
      and third stage; hepatic maturation. At the end of differentiation culture,
      hepatocytes induced from human pluripotent stem cells expressed hepatocyte
      specific proteins, such as alpha-fetoprotein, albumin, alpha1 antitrypsin and
      cytochrome P450 (CYP3A4), at similar or higher levels compared with three control
      human hepatocyte or hepatic cell lines. These human iPS/ES cell-derived
      hepatocytes also showed mature hepatocyte functions: indocyanine green dye uptake
      (~ 30%), storage of glycogen (>80%) and metabolic activity of CYP3A4.
      Furthermore, they produced a highly sensitive hepatotoxicity assay system for D
      galactosamine as determined by the extracellular release of hepatocyte-specific
      enzymes. Hepatoprotective prostaglandin E1 attenuated this toxicity.
      Interestingly, bile duct-specific enzymes were also detected after drug
      treatment, suggesting the presence of bile-duct epithelial cells (cholangiocytes)
      in our culture system. Electron microscopic studies confirmed the existence of
      cholangiocytes, and an immunostaining study proved the presence of bipotential
      hepatoblasts with high potential for proliferation. Differentiated cells were
      transferrable onto new dishes, on which small-sized proliferating cells with
      hepatocyte markers emerged and expanded. Thus, our differentiation culture system
      provides mature functional hepatocytes, cholangiocytes, and their progenitors
      with proliferative potential from a wide variety of human pluripotent stem cells.

PMID- 22384929
TI  - Enucleated ovine oocyte supports human somatic cells reprogramming back to the
      embryonic stage.
AB  - Increased possibility of universality of ooplasmic reprogramming factors resulted
      in a parallel increased interest to use interspecies somatic cell nuclear
      transfer (iSCNT) to address basic questions of developmental biology and to
      improve the feasibility of cell therapy. In this study, the interactions between
      human somatic cells and ovine oocytes were investigated. Nuclear remodeling
      events were first observed 3 h post-iSCNT as nuclear swelling, chromosome
      condensation, and spindle formation. A time-dependent decrease in maturation
      promoting activity of inactivated reconstructs coincided with increased
      aberrations in chromosome and spindle organization of the newly developed
      embryos. The sequence and duration of nuclear remodeling events were irrespective
      of donor cell type used. Although the majority of the reconstituted embryos
      arrested before embryonic genome activation (8-16-cell) stage, less than 5% of
      them could progress beyond transcription-requiring developmental stage and formed
      blastocyst-like structures with distinct inner cell mass and trophectoderm at
      days 7 and 8 post-SCNT. Importantly, real-time assessment of three
      developmentally important genes (Oct4, Sox2, and Nanog) indicated their
      upregulation in iSCNT blastocysts. Blastocyst-derived outgrowths had alkaline
      phosphatase activity that was lost upon passage. Collectively, this study
      introduced ovine oocyte as a credible cytoplast for remodeling and reprogramming
      of human somatic cells back to the embryonic stage and provided a platform for
      further studies to unravel possible differences exist between reprogramming
      ability of oocytes of different mammalian species.

PMID- 22384930
TI  - MicroRNA-193 pro-proliferation effects for bone mesenchymal stem cells after low
      level laser irradiation treatment through inhibitor of growth family, member 5.
AB  - The enhanced proliferation of mesenchymal stem cells (MSCs) can be helpful for
      the clinical translation of cell therapy. Low-level laser irradiation (LLLI) has
      been demonstrated as regulating MSC proliferation. MicroRNAs (miRNAs) are
      involved in various pathophysiologic processes in stem cells, but the role of
      miRNAs in the LLLI-based promotion of MSC proliferation remains unclear. We found
      that the proliferation level and cell cycle-associated genes in MSCs were
      increased after LLLI treatment in a time-dependent manner. Microarray assays
      revealed subsets of miRNAs to be differentially regulated, and these dynamic
      changes were confirmed by quantitative real-time polymerase chain reaction (qRT
      PCR) after LLLI. miR-193 was the most highly up-regulated miRNA, and the change
      in it was related with the proliferation level. Gain-loss function experiments
      demonstrated that miR-193 could regulate the proliferation of MSCs, including
      human's and rat's, but could not affect the apoptosis and differentiation level.
      Blockade of miR-193 repressed the MSC proliferation induced by LLLI. By qRT-PCR,
      we found that miR-193, in particular, regulated cyclin-dependent kinase 2 (CDK2)
      expression. Bioinformatic analyses and luciferase reporter assays revealed that
      inhibitor of growth family, member 5 (ING5) could be the best target of miR-193
      to functionally regulate proliferation and CDK2 activity, and the mRNA and
      protein level of ING5 was regulated by miR-193. Furthermore, the ING5 inhibited
      by small interfering RNA (siRNA) could up-regulate the proliferation of MSCs and
      the expression of CDK2. Taken together, these results strongly suggest that miR
      193 plays a critical part in MSC proliferation in response to LLLI stimulation,
      which is potentially amenable to therapeutic manipulation for clinical
      application.

PMID- 22384931
TI  - Creating the socially marginalised youth smoker: the role of tobacco control.
AB  - We discuss how the tobacco control discourse on youth smoking in Canada appears
      to be producing and constituting socially marginalised smokers. We analyse
      material from a study on social inequalities in Canadian youth smoking.
      Individual interviews were conducted in 2007 and 2008 with tobacco control
      practitioners specialising in youth smoking prevention in British Columbia and
      Quebec. We found that the discourse on youth smoking is creating a set of
      divisive practices, separating youths who have a capacity for self-control from
      those who do not, youths who are able to make responsible decisions from those
      who are not - with these distinctions often framed as a function of social class.
      Youths who smoke were not described simply as persons who smoke cigarettes but as
      individuals who, through their economic and social marginalisation, are
      biologically fated and behaviourally inclined to be smokers. This 'smokers' risk'
      discourse obscures the social structural conditions under which people smoke and
      reproduces the biological and behavioural reductionism of biomedicine. The
      collision of risk and class in the discourse on poor youth who smoke may not only
      be doubly burdening but may intensify social inequalities in youth smoking by
      forming subcultures of resistance and risk-taking.

PMID- 22384932
TI  - Individual neuropsychological profiles at age 51/2 years in children born preterm
      in relation to medical risk factors.
AB  - Follow-up studies of preterm children have reported a range of cognitive
      deficits, particularly in executive functions, visuospatial abilities, and
      learning. However, few researchers have adopted a person-oriented approach,
      exploring individual neuropsychological profiles. The aim of this study was to
      identify typical neuropsychological profiles among preterm children and control
      children, respectively. A second aim was to investigate if neuropsychological
      profiles at age 51/2 might be associated with perinatal medical risk factors. As
      part of the longitudinal Stockholm Neonatal Project, NEPSY for 4- to 7-year-old
      children ( Korkman, 1990 ), WPPSI-R, and Movement ABC were administered at age
      51/2 years to 145 preterm (mean gestational age 28 weeks) and 117 control
      children born at term. For the present study, the NEPSY results of each child
      were transformed into summary z scores for each of 5 neuropsychological domains:
      attention, memory, sensory-motor, verbal, and visuospatial functions.
      Subsequently, Ward's cluster analysis was performed for the preterm and control
      groups separately, identifying 5 neuropsychological profiles in both groups
      explaining around 56% and 57% of the variance, respectively. Overall, preterm
      children had lower neuropsychological results but also more diverging profiles
      compared to controls. The variability in outcome could not be sufficiently
      explained by birth weight, gestational age, or medical risks. The results suggest
      that prematurity interacts dynamically with genetic, medical, and environmental
      factors in neuropsychological development.

PMID- 22384933
TI  - Chiropractic or osteopathic manipulation for children in the United States: an
      analysis of data from the 2007 National Health Interview Survey.
AB  - OBJECTIVES: The aim of this study was to describe use of chiropractic and/or
      osteopathic manipulation by children in the United States along with the specific
      health conditions for which they sought care. METHODS: The study was a secondary
      data analysis of the National Health Interview Survey 2007, Child Alternative
      Medicine file as well as the Child Core Sample. National population estimates
      were generated for reported use of chiropractic or osteopathic manipulation
      (C/OM) by children for specific health conditions. Odds ratios (OR) and 95%
      confidence intervals (CI) were generated from binary logistic regression models
      that assessed the likelihood that children of specific characteristics would use
      this therapy. RESULTS: National estimates indicated that 2.3 million children
      (2.3%) in the United States had used C/OM in 2007. C/OM was the most common
      complementary and alternative medicine procedure. Children aged 12-18 years were
      more likely to have seen these providers than were younger age groups (OR=3.4
      [95% CI, 2.1-5.5]). Homeopathy (1.2%), massage (1.0), and naturopathy (0.3%) were
      the next most common procedures. The most common complaints were back and neck
      pain. Other conditions for which children were seen included other
      musculoskeletal conditions, sinusitis, allergies, and nonmigraine headaches.
      Racial categories did not differ significantly regarding use of manipulation, but
      those children with both mother and father in the household were more likely to
      have used this form of care (OR=1.7 [95% CI, 1.1-2.6]). CONCLUSIONS: C/OM is
      primarily used for back and neck pain, which is increasing in prevalence in
      children. Teens are more likely to use it than are younger children.

PMID- 22384934
TI  - Real-life experience of managing vulval erosive lichen planus: a case-based
      review and U.K. multicentre case note audit.
AB  - BACKGROUND: There is a lack of published evidence for treatment and outcome
      measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a
      multicentre case note review to examine real-life management of ELPV comparing
      current U.K. practice against an agreed audit standard. METHODS: Criteria for
      standards of care for which to evaluate current service provision were set
      following communication with experts from the British Society for the Study of
      Vulval Disease. Participants from 10 U.K. centres included nine dermatologists
      and one gynaecologist who run specialist vulval clinics. Standards examined the
      documentation of disease severity/impact measures, the use of diagnostic
      biopsies, treatments used and assessment of treatment response. RESULTS: Audit
      data were collected from 172 patients. Documentation of symptoms/clinical
      findings was excellent (99%, 170/172). A schematic diagram was present in the
      notes of 87% (150/172). Patient-related disease impact measures including
      Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172)
      were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135)
      showed histological features consistent with erosive lichen planus. Squamous cell
      carcinoma developed in four patients (two vulval, two oral) and vulval
      intraepithelial neoplasia in two further patients. Recommended first-line
      treatment with a very potent topical steroid was used in 75% (129/172) with
      improvement in 66% (85/129). Significant variation in second-line therapy was
      seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of
      standardized guidance for treating ELPV and the need for vulval-specific
      outcomes. This audit should act as a framework towards improving ELPV management
      and to plan future research in this area.

PMID- 22384935
TI  - Predicting regioselectivity in nucleophilic aromatic substitution.
AB  - We have investigated practical and computationally efficient methods for the
      quantitative prediction of regioisomer distribution in kinetically controlled
      nucleophilic aromatic substitution reactions. One of the methods is based on
      calculating the relative stabilities of the isomeric sigma-complex intermediates
      using DFT. We show that predictions from this method can be used quantitatively
      both for anionic nucleophiles with F(-) as leaving group, as well as for neutral
      nucleophiles with HF as leaving group. The sigma-complex approach failed when the
      leaving group was Cl/HCl or Br/HBr, both for anionic and neutral nucleophiles,
      because of difficulties in finding relevant sigma-complex structures. An approach
      where we assumed a concerted substitution step and used such transition state
      structures gave quantitatively useful results. Our results are consistent with
      other theoretical works, where a stable sigma-complex has been identified in some
      cases, whereas others have been indicated to proceed via a concerted substitution
      step.

PMID- 22384936
TI  - Cost analysis of robot-assisted laparoscopic versus hand-assisted laparoscopic
      partial nephrectomy.
AB  - PURPOSE: To perform a cost comparison of three approaches to partial nephrectomy
      (PN): Open (OPN), hand-assisted laparoscopic (HALPN), and robot-assisted (RAPN).
      PATIENTS AND METHODS: We retrospectively evaluated cost and clinical data from
      patients undergoing OPN, HALPN, and RAPN from 2007 to 2010 (n=89). Baseline
      demographic data, patient comorbidities, R.E.N.A.L. nephrometry score, and
      perioperative outcomes were assessed. Costs and subcosts from the operating room
      (OR) and hospital were evaluated using nonparametric statistical analyses.
      RESULTS: Patient demographics and tumor characteristics were similar between
      HALPN and RAPN, while OPN patients had more comorbidities and more difficult-to
      resect tumors. Thus, HALPN and RAPN were directly compared, while OPNs were
      excluded from the analysis. No difference was found in overall costs between
      HALPN and RAPN ($13,560 vs $13,439, P=0.29). OR costs were higher for RAPN ($7276
      vs $5708, P=0.0001) because of the higher robotic capital and reusable equipment
      costs that outweighed higher disposable costs in the HALPN group. OR time-related
      costs were similar between groups. RAPN patients had a shorter length of stay
      (LOS), which decreased postoperative hospital costs ($4371 vs $5984, P=0.002).
      CONCLUSIONS: No difference in overall cost was found between RAPN and HALPN.
      Robot allocation, OR equipment use, and LOS are important determinants of total
      cost. Further study regarding recovery and quality of life may reveal added
      benefits to minimally invasive approaches and increase use of nephron-sparing
      surgery.

PMID- 22384937
TI  - Involvement of Ca2+ and ATP in enhanced gene delivery by bubble liposomes and
      ultrasound exposure.
AB  - Recently, we reported the accelerated gene transfection efficiency of laminin
      derived AG73-peptide-labeled polyethylene glycol-modified liposomes (AG73-PEG
      liposomes) and cell penetrating TAT-peptide labeled PEG liposomes using PEG
      modified liposomes, which trap echo-contrast gas, "Bubble liposomes" (BLs), and
      ultrasound (US) exposure. BLs and US exposure were reported to enhance the
      endosomal escape of AG73-PEG liposomes, thereby leading to increased gene
      expression. However, the mechanism behind the effect of BLs and US exposure on
      endosomes is not well understood. US exposure was reported to induce an influx of
      calcium ions (Ca2+) by enhancing permeability of the cell membrane. Therefore, we
      examined the effect of Ca2+ on the endosomal escape and transfection efficiency
      of AG73-PEG liposomes, which were previously enhanced by BLs and US exposure. For
      cells treated with EGTA, the endosomal escape and gene expression of AG73-PEG
      liposomes were not enhanced by BLs and US exposure. Similarly, transfection
      efficiency of the AG73-PEG liposomes in ATP-depleted cells was not enhanced. Our
      results suggest that Ca2+ and ATP are necessary for the enhanced endosomal escape
      and gene expression of AG73-PEG liposomes by BLs and US exposure. These findings
      may contribute to the development of useful techniques to improve endosomal
      escape and achieve efficient gene transfection.

PMID- 22384938
TI  - Vertical and horizontal photobiont transmission within populations of a lichen
      symbiosis.
AB  - Lichens are widespread symbioses and play important roles in many terrestrial
      ecosystems. The genetic structure of lichens is the result of the association
      between fungal and algal populations constituting the lichen thallus. Using eight
      fungus- and seven alga-specific highly variable microsatellite markers on within
      population spatial genetic data from 62 replicate populations across Europe,
      North America, Asia and Africa, we investigated the contributions of vertical and
      horizontal transmission of the photobiont to the genetic structure of the
      epiphytic lichen Lobaria pulmonaria. Based on pairwise comparisons of multilocus
      genotypes defined separately for the mycobiont and for the photobiont, we
      inferred the transmission mode of the photobiont and the relative contribution of
      somatic mutation and recombination. After constraining the analysis of one
      symbiont to pairs of individuals with genetically identical symbiotic partners,
      we found that 77% of fungal and 70% of algal pairs were represented by clones.
      Thus, the predominant dispersal mode was by means of symbiotic vegetative
      propagules (vertical transmission), which dispersed fungal and algal clones co
      dependently over a short distance, thus shaping the spatial genetic structure up
      to distances of 20m. Evidence for somatic mutation generating genetic diversity
      was found in both symbionts, accounting for 30% of pairwise comparisons in the
      alga and 15% in the fungus. While the alga did not show statistically significant
      evidence of recombination, recombination accounted for 7.7% of fungal pairs with
      identical algae. This implies that, even in a mostly vegetatively reproducing
      species, horizontal transmission plays a role in shaping the symbiotic
      association, as shown in many coral and other symbioses in nature.

PMID- 22384939
TI  - Phosphoenolpyruvate phosphotransferase system regulates detection and processing
      of the quorum sensing signal autoinducer-2.
AB  - Autoinducer-2 (AI-2) a signal produced by a range of phylogenetically distant
      microorganisms, enables inter-species cell-cell communication and regulates many
      bacterial phenotypes. Certain bacteria can interfere with AI-2-regulated
      behaviours of neighbouring species by internalizing AI-2 using the Lsr transport
      system (encoded by the lsr operon). AI-2 imported by the Lsr is phosphorylated by
      the LsrK kinase and AI-2-phosphate is the inducer of the lsr operon. Here we show
      that in Escherichia coli the phosphoenolpyruvate phosphotransferase system (PTS)
      is required for Lsr activation and is essential for AI-2 internalization.
      Although the phosphorylation state of Enzyme I of PTS is important for this
      regulation, LsrK is necessary for the phosphorylation of AI-2, indicating that AI
      2 is not phosphorylated by PTS. Our results suggest that AI-2 internalization is
      initiated by a PTS-dependent mechanism, which provides sufficient intracellular
      AI-2 to relieve repression of the lsr operon and, thus induce depletion of AI-2
      from the extracellular environment. The fact that AI-2 internalization is not
      only controlled by the community-dependent accumulation of AI-2, but also depends
      on the phosphorylation state of PTS suggests that E. coli can integrate
      information on the availability of substrates with external communal information
      to control quorum sensing and its interference.

PMID- 22384940
TI  - Trends and morbidity associated with oxytocin use in labour in nulliparas at
      term.
AB  - AIM: To determine the trends in oxytocin use at a population level within New
      South Wales and to assess the maternal and neonatal morbidities associated with
      the use of oxytocin. METHODS: Trends in oxytocin use were assessed for women in
      NSW who were nulliparas at term with a singleton, cephalic fetus between 1998 and
      2008. Maternal and neonatal morbidities were assessed in 2007-2008 using linked
      hospital and birth data with regression analysis. Oxytocin was also assessed by
      indication for use being either induction or augmentation of labour. RESULTS: The
      overall use of oxytocin increased from 10,291 (36.5%) of births in 1998 to 14,440
      (45.4%) of births in 2008 (P < 0.0001) with the increase entirely because of the
      increased use for induction of labour. The use of oxytocin was associated with an
      increase in regional analgesia (65 to 22%), instrumental delivery (21 to 18%) and
      caesarean section (29 to 14%) as compared to women who did not receive oxytocin
      in labour. Oxytocin was also associated with an increase in severe maternal
      adjusted odds ratios ((aOR) 1.48, 95% CI 1.30-1.68) and neonatal morbidity (aOR
      1.29, 95% CI 1.17-1.41). This increase in morbidity was maintained when both
      augmentation and induction were assessed separately. CONCLUSION: Oxytocin has an
      important role in the management of labour. However, its use should be carefully
      monitored with standardised treatment regimes to minimise maternal and neonatal
      morbidity.

PMID- 22384941
TI  - International survey on gestational diabetes.
AB  - OBJECTIVE: There is a lack of consensus among guidelines for screening, diagnosis
      and management of gestational diabetes (GDM). The purpose of this project was to
      determine current practices around GDM amongst members of the Medical Women's
      International Association (MWIA). METHODS: The MWIA with the Division of
      Endocrinology and Metabolism, University of Ottawa, developed an online survey
      using "Survey Monkey" and distributed it to its members. RESULTS: A total of 125
      members completed the survey. Universal screening was recommended by 83% and most
      followed published guidelines. The 50 g glucose challenge test (GCT) was used for
      screening by 23% of participants while 25% recommended fasting blood glucose.
      There was also variability in how to proceed following a positive screening test.
      Almost 65 % recommended one of the glucose tolerance tests (50 g OGTT 26.7 % vs.
      75 g OGTT 25.6% vs. 100 g OGTT 12.2%), while 18.8% recommended starting treatment
      and 16.7% used other diagnostic measures. Insulin was the most recommended
      treatment (75%) if diet/lifestyle failed. CONCLUSIONS: Our survey highlights the
      international variability that exists in the screening, diagnosis, and management
      of women with GDM. These differences impact on true prevalence rates and may
      underestimate the costs of this disease. The recommendation to move to a single
      internationally accepted diagnostic algorithm may be hampered by the variation in
      current practice globally.

PMID- 22384943
TI  - Effects of weather variability and air pollutants on emergency admissions for
      cardiovascular and cerebrovascular diseases.
AB  - We examined the effect of ambient temperature, air pressure and air pollutants on
      daily emergency admissions by identifying the cause of admission for each type of
      stroke and cardiovascular disease using generalized linear Poisson regression
      models allowing for overdispersion, and controlling for seasonal and inter-annual
      variations, days of the week and public holidays, levels of influenza and
      respiratory syncytial viruses. Every 1 degrees C decrease in mean temperature was
      associated with an increase in the daily number of emergency admissions by 7.83%
      (95% CI 2.06-13.25) for acute coronary syndrome (ACS) and heart failure, by
      35.57% (95% CI 15.59-59.02) for intracerebral haemorrhage (ICH) and by 11.71%
      (95% CI 4.1-19.89) for cerebral infarction. An increase of emergency admissions
      due to ICH (3.25% (95% CI 0.94-5.51)), heart failure (3.56% (95% CI 1.09-5.96))
      was observed at every 1 hPa decrease in air pressure from the previous days. We
      found stronger detrimental effect of cold on stroke than cardiovascular disease.

PMID- 22384944
TI  - Endoscopic dacryocystorhinostomy without silicone stent.
AB  - CONCLUSION: In nasolacrimal duct (NLD) obstruction patients that undergo
      endoscopic dacryocystorhinostomy (DCR), creation of a patent rhinostomy with
      adequate epithelialization can be accomplished without a stent. However, in
      common canalicular obstruction patients, a silicone stent seems to have a
      beneficial role and to bear more favorable results. OBJECTIVES: The aim of this
      study was to evaluate the surgical outcome of endoscopic DCR without the use of a
      silicone stent. METHODS: In all, 36 patients (41 eyes) who underwent endoscopic
      DCR were enrolled in this study. The patients were classified into a DCR with
      silicone stent group and a DCR without silicone stent group. Then each of the
      groups was subdivided into common canalicular obstruction group and NLD
      obstruction group. Surgical outcomes were evaluated by postoperative symptom
      improvement and patency of the rhinostomy under nasal endoscopic exam. RESULTS:
      The epiphora was improved in 84.2% of the silicone stent group and 81.8% of the
      non-silicone stent group. Categorized by the level of obstruction, in common
      canalicular obstruction, the success rate was 84.5% (11/13) in the silicone stent
      group and 57.1% (4/7) in the no stent group. In NLD obstruction, the success rate
      was 83.0% (5/6) in the silicone stent group and 93.3% (14/15) in the no stent
      group.

PMID- 22384945
TI  - The mediating effects of perceived parental teasing on relations of body mass
      index to depression and self-perception of physical appearance and global self
      worth in children.
AB  - AIM: To report a correlational study of the relation of body mass index to
      children's perceptions of physical appearance and global self-worth and
      depression, as mediated by their perceptions of parental teasing. BACKGROUND: The
      relation between depression and self-perception in children with obesity has been
      reported. Recently, parental factors were found to be related to childhood
      obesity. Little is known about the effects of perceived parental teasing on
      depression and self-perception in children. DESIGN: A descriptive correlational
      research design was used. METHODS: Data were collected from 455 children in the
      fifth and sixth grades in four provinces of South Korea using self-report
      questionnaires for measuring self-perception of physical appearance and global
      self-worth, depression and perceived parental teasing between October-December in
      2009. The children's weight and height information from school health records was
      used. Multiple regression analysis and the Sobel test were used to identify the
      mediating effect of perceived parental teasing. RESULTS: Among the children, 20%
      were overweight or obese. Although children with obesity did not differ in the
      level of depression from their normal weight counterparts, they demonstrated
      lower perceived physical appearance and higher perceived parental teasing. The
      mediating effects of perceived parental teasing were found for the relations
      between body mass index and self-perception of physical appearance and global
      self-worth, and body mass index and depression, respectively. CONCLUSION: Obese
      children at risk of parental teasing should be identified to prevent their
      psychological problems. A well-designed intervention study is necessary to
      examine the effects of psycho-emotional interventions for obese children.

PMID- 22384946
TI  - Multiobjective prioritization methodology and decision support system for
      evaluating inventory enhancement strategies for disrupted interdependent sectors.
AB  - Disruptions in the production of commodities and services resulting from
      disasters influence the vital functions of infrastructure and economic sectors
      within a region. The interdependencies inherent among these sectors trigger the
      faster propagation of disaster consequences that are often associated with a
      wider range of inoperability and amplified losses. This article evaluates the
      impact of inventory-enhanced policies for disrupted interdependent sectors to
      improve the disaster preparedness capability of dynamic inoperability input
      output models (DIIM). In this article, we develop the dynamic cross
      prioritization plot (DCPP)--a prioritization methodology capable of identifying
      and dynamically updating the critical sectors based on preference assignments to
      different objectives. The DCPP integrates the risk assessment metrics (e.g.,
      economic loss and inoperability), which are independently analyzed in the DIIM.
      We develop a computer-based DCPP tool to determine the priority for inventory
      enhancement with user preference and resource availability as new dimensions. A
      baseline inventory case for the state of Virginia revealed a high concentration
      of (i) manufacturing sectors under the inoperability objective and (ii) service
      sectors under the economic loss objective. Simulation of enhanced inventory
      policies for selected critical manufacturing sectors has reduced the recovery
      period by approximately four days and the expected total economic loss by $33
      million. Although the article focuses on enhancing inventory levels in
      manufacturing sectors, complementary analysis is recommended to manage the
      resilience of the service sectors. The flexibility of the proposed DCPP as a
      decision support tool can also be extended to accommodate analysis in other
      regions and disaster scenarios.

PMID- 22384947
TI  - Island pedicle flaps for medial canthus repair.
AB  - BACKGROUND: The medial canthus is a frequent site for skin cancer and
      reconstruction after Mohs surgery can prove to be challenging. In the literature
      various reconstruction methods are recommended for these cases. Flap
      reconstructions are mostly transposition flaps from the glabella, skin with
      different properties from that in the canthal region, hence mostly requiring
      correction in a second stage. OBJECTIVES: To ascertain the utility of a different
      reconstruction method, applying island pedicle flaps for medial canthal lesions
      and obviating the necessity for second-stage corrections. METHODS: A review was
      undertaken of the medical records and photographs of patients who had a pedicle
      island flap reconstruction for medial canthal defects after Mohs surgery. There
      were four different possibilities: a pedicle island flap from the cheek, the back
      of the nose or the glabella or a combination of these flaps. RESULTS: Sixteen
      patients were reconstructed by pedicle island flaps for defects of the medial
      canthal area. A follow-up for all patients after 1 year indicated that all
      patients showed good to excellent results. No cases of web deformation and
      ectropion were found. CONCLUSIONS: This flap is not mentioned in textbooks in
      reference to the reconstruction of canthal lesions and its value for this
      particular location is probably underestimated.

PMID- 22384948
TI  - Protocols and participatory democracy in a 'North-South' product development
      partnership.
AB  - Global product development partnerships (PDPs) for new health technologies have
      become an increasingly important part of the science and development landscape
      over the past two decades. Polarised positions are adopted by those scrutinising
      the power and governance of these public-private formations; on the one hand,
      they are seen as successful social technology innovations, on the other as
      regressive and imperialistic regimes of neo-colonialism. Answering recent calls
      for research to examine the actors, governance, context and dynamics of PDPs,
      this article presents a sociological case study of one particular partnership,
      the Microbicides Development Programme (MDP). Interviews were conducted with a
      cross-section of programme staff in the UK and Zambia, and discourses analysed
      through a Foucauldian lens of governmentality. This article suggests that two
      tools of government were central to MDP's cohesiveness: institutional discourses
      of participatory democracy and capacity building and scientific protocols.
      Through these material-semiotic tools, the scientific community, junior
      operational researchers and the funder were successfully enrolled into the
      programme and governed by a central body based in the UK. This article draws on
      Nikolas Rose's work to discuss these socio-scientific discourses as technologies
      of government, and provides a non-dualistic account of power and governance in a
      North-South PDP.

PMID- 22384949
TI  - Psychiatric nursing as 'different' care: experience of Iranian mental health
      nurses in inpatient psychiatric wards.
AB  - Patients with mental illness require unique and specific care. The purpose of
      this study was to explore the experiences of nurses, who provide such care for
      mentally ill people, within the context of Iranian culture. This hermeneutic
      phenomenological study was carried out in a university-affiliated hospital in an
      urban area of Iran. We interviewed 10 mental health nurses to capture in detail
      their experiences in psychiatric units, and the approach developed by Diekelmann
      et al. was employed to analyse the data. Four themes and five sub-themes were
      identified: 'being engaged with patients' (sub-themes: 'struggle for
      monitor/control', 'safety/security concerns', 'supporting physiological and
      emotional needs'), 'being competent', 'altruistic care' and 'facing difficulties
      and challenges' (sub-themes: 'socio-cultural' and 'organizational challenges').
      The results provide valuable insights and greater understanding of the
      professional experiences of psychiatric nurses in Iran, and indicate the need for
      a stable and responsible organizational structure for those nurses who are
      expected to manage patient care in psychiatric wards.

PMID- 22384950
TI  - Detection of anti-Lepore Hb P-Nilotic by multiplex ligation-dependent probe
      amplification.
AB  - Anti-Lepore hemoglobins (Hbs) are rare betadelta fusion variants that arise from
      non homologous crossover during meiosis. We describe the application of multiplex
      ligation-dependent probe amplification (MLPA) to test for a suspected anti-Lepore
      Hb in an individual with an ambiguous Hb variant detected on routine screening by
      electrophoresis and high performance liquid chromatography (HPLC). The results of
      MLPA revealed duplication of beta and delta gene segments consistent with an anti
      Lepore betadelta fusion gene. Resolution of the hybrid gene by DNA sequencing
      identified the variant as Hb P-Nilotic (beta31-delta50) HBB/HBD hybrid; HBB
      through 22; HBD from 50 (NG_000007.3:g.63290_70702dup). Multiples ligation
      dependent probe amplification allows for rapid detection of hybrid globin
      variants caused by duplications in the beta-globin gene locus.

PMID- 22384951
TI  - Evaluation of pediatric percutaneous nephrolithotomy experience of an adult
      trained surgeon.
AB  - PURPOSE: The aim of our study is to evaluate the pediatric percutaneous
      nephrolithomy (PCNL) learning curve of a surgeon. PATIENTS AND METHODS: The cases
      of the first 70 pediatric patients with renal stone disease who underwent PCNL by
      a surgeon who had performed 120 PCNLs on adults at our clinic were analyzed
      retrospectively. The patients were divided into two groups depending on their
      date of surgery (n=35), and the localization of the stone, stone burden, access
      numbers on the kidney, stone-free rates, blood transfusion in the perioperative
      postoperative period, duration of hospitalization, and complications were
      recorded. RESULTS: The mean of patients in group 1 was 11.45 +/- 3.93 (2-16)
      years, while the same value for group 2 was 8.42 +/- 4.21 (1-16) years (P<0.005).
      There was no statistically significant difference between the two groups
      regarding stone surface area (group 1: 332.57 +/- 192.46 [100-700] mm(2); group
      2: 322.85 +/- 165.20 [150-900] mm(2)), number of access, stone localization,
      duration of hospitalization, duration of surgery, blood replacement, and Double-J
      implantation (P>0.005). While the stone-free rate was 82.85% for group 1, it was
      100% for group 2 (P>0.005). CONCLUSIONS: Pediatric PCNL can be performed safely
      after 120 adult PCNL procedures, although this number varies from one surgeon to
      another. After the first 35 pediatric PCNL experiences, PCNL can safely be
      performed even on very young children, and higher stone-free rates can be
      obtained.

PMID- 22384952
TI  - Rapid discrimination and characterization of vanilla bean extracts by attenuated
      total reflection infrared spectroscopy and selected ion flow tube mass
      spectrometry.
AB  - Vanilla beans have been shown to contain over 200 compounds, which can vary in
      concentration depending on the region where the beans are harvested. Several
      compounds including vanillin, p-hydroxybenzaldehyde, guaiacol, and anise alcohol
      have been found to be important for the aroma profile of vanilla. Our objective
      was to evaluate the performance of selected ion flow tube mass spectrometry (SIFT
      MS) and Fourier-transform infrared (FTIR) spectroscopy for rapid discrimination
      and characterization of vanilla bean extracts. Vanilla extracts were obtained
      from different countries including Uganda, Indonesia, Papua New Guinea,
      Madagascar, and India. Multivariate data analysis (soft independent modeling of
      class analogy, SIMCA) was utilized to determine the clustering patterns between
      samples. Both methods provided differentiation between samples for all vanilla
      bean extracts. FTIR differentiated on the basis of functional groups, whereas the
      SIFT-MS method provided more specific information about the chemical basis of the
      differentiation. SIMCA's discriminating power showed that the most important
      compounds responsible for the differentiation between samples by SIFT-MS were
      vanillin, anise alcohol, 4-methylguaiacol, p
      hydroxybenzaldehyde/trimethylpyrazine, p-cresol/anisole, guaiacol, isovaleric
      acid, and acetic acid. ATR-IR spectroscopy analysis showed that the
      classification of samples was related to major bands at 1523, 1573, 1516, 1292,
      1774, 1670, 1608, and 1431 cm(-1) , associated with vanillin and vanillin
      derivatives.

PMID- 22384953
TI  - Purification of a novel pepsin inhibitor from Coriolus versicolor and its
      biochemical properties.
AB  - A novel pepsin inhibitor was isolated from Coriolus versicolor. The purification
      was carried out by a 2-step ultrafiltration followed by DEAE-52 and Mono Q ion
      exchange chromatography. SDS-PAGE and gel filtration chromatography analysis
      showed that the isolated inhibitor was a 22.3 kDa protein with a single subunit.
      Heat stability of this inhibitor was estimated and only 7% of its inhibitory
      activity lost after treatment at 98  degrees C. The inhibitor was more specific
      against pepsin than several other proteases. The dissociation constant (K(i)) and
      concentration required for 50% pepsin inhibition (IC50) were 5.84 * 10(-5) M and
      26.26 MUg/mL, respectively. Apparent decrease of alpha-helix and increase of
      random coil were observed in the circular dichroism spectra of pepsin when an
      equimolar amount of the inhibitor was added. The inhibition mechanism of this
      inhibitor differs from the reported aspartic protease inhibitors, according to
      the secondary structure and the kinetic studies of this inhibitor.

PMID- 22384954
TI  - Black rice bran as an ingredient in noodles: chemical and functional evaluation.
AB  - This study examined the feasibility of using black rice bran (BRB) as an
      ingredient of noodles and evaluated the effect of BRB incorporation in noodles in
      terms of chemical and functional attributes. Noodles were prepared with BRB as an
      ingredient at different levels (2%, 5%, 10%, and 15%). Addition of BRB (5%, 10%,
      and 15%) significantly decreased the cohesiveness of noodles in texture
      evaluation. Noodles with different levels of BRB were functionally evaluated and
      content of polyphenolics, flavonoids, and anthocyanins were improved compared to
      the control. Additionally, antioxidant activity of BRB noodles was increased
      compared to the control. BRB can be an excellent ingredient to increase the
      nutritional value and antioxidant properties of noodles.

PMID- 22384955
TI  - Physical and chemical stability of tagatose powder.
AB  - Tagatose is a reduced-calorie monosaccharide that displays prebiotic properties.
      Water can interact with powdered tagatose to varying extents, depending upon the
      storage environment. Adsorbed water can impact the stability of tagatose,
      altering its functionality and usability as an ingredient. The objective of this
      study was to evaluate the physical and chemical stability of bulk tagatose powder
      as a function of relative humidity (RH) and temperature. Powdered tagatose was
      stored in desiccators at 20, 30, and 40  degrees C and 33% to 85% RH. Moisture
      contents (MC), physical characteristics, tagatose degradation profiles, and
      browning kinetics were monitored for 12 mo. The critical RH associated with
      deliquescence (RH0) was approximately 85% at 20  degrees C. MC values below RH0
      were all less than 2% (wb). The MC at 85% RH ranged from 55% to 80% (wb),
      increasing as temperature decreased. At 33% RH and 20  degrees C tagatose
      remained a free flowing powder. As either temperature or RH increased, varying
      degrees of physical caking occurred. At 85% RH, tagatose deliquesced at all
      temperatures. Browning occurred in all samples at 40  degrees C. Despite physical
      caking and browning, measurable tagatose degradation was only observed in the
      deliquesced sample at 85% RH and 40  degrees C, where 20% loss occurred in 6 mo.
      Although extreme RHs and temperatures are required for tagatose degradation to
      occur, intermediate RHs and temperatures promote physical caking and
      deliquescence, which create handling problems during product formulation. The
      exposure of tagatose to elevated relative humidities and temperatures should be
      avoided to maintain its physical and chemical quality.

PMID- 22384956
TI  - Effects of L-ascorbic acid on physicochemical characteristics of wheat starch.
AB  - The main objective of this study was to determine the effects of l-ascorbic acid,
      as a permitted additive in bakery products, on characteristics of wheat starch.
      Suspensions of wheat starch (30%, w/w) in water containing 140 mg/kg ascorbic
      acid before and after gelatinization were prepared and studied using different
      techniques. The results of scanning electron microscopy showed that some spots
      appeared on the surface of the starch granules as a result of the addition of
      ascorbic acid. However, no changes in the starch crystalline pattern and its
      degree of crystallinity were observed by X-ray diffraction technique. For
      ungelatinized samples, no difference in the pasting properties of the samples was
      determined by the rapid visco analyzer, whereas for the gelatinized samples, peak
      and final viscosities decreased for the samples contained ascorbic acid.
      Determination of the intrinsic viscosities of the samples showed that addition of
      ascorbic acid to the gelatinized samples reduced the intrinsic viscosity. In
      general, it was found that ascorbic acid had some degradation effects on wheat
      starch molecules particularly after gelatinization.

PMID- 22384957
TI  - Assessment of the validity of maturity metrics for predicting the volatile
      composition of Concord grape juice.
AB  - Total soluble solids (TSS) are typically used as the sole metric for maturity of
      Concord grapes. However, the reliability of TSS in predicting the aroma
      composition of finished juice for grapes sourced from multiple sites has not been
      investigated. This study sought to determine the validity of TSS in predicting
      the aroma composition of the juice while also investigating other potentially
      useful indicators, including pH, titratable acidity (TA), and TSS:TA ratio.
      Grapes were harvested from 9 sites in the Lake Erie Concord Grape Belt and
      stratified from north to south and east to west. The key aroma compounds methyl
      anthranilate ("grapey") and trans-2-hexenal ("herbaceous") were quantified along
      with several other odorants. It was observed that while TSS was a robust
      predictor of monomeric anthocyanin content across sites, it was a poor predictor
      of aroma compounds in the finished juice. Conversely, pH, TA, and TSS:TA ratio
      were all significantly correlated with methyl anthranilate and trans-2-hexenal
      concentrations (P < 0.05) in samples equal to or exceeding 15 Brix, the industry
      minimum for grape maturity. These results indicate that parameters related to
      acidity are better predictors of aroma composition than TSS, which may aid in
      efforts to minimize herbaceous off-aromas and optimize the aroma composition of
      the finished juice.

PMID- 22384958
TI  - Effect of the type of oil on the evolution of volatile compounds of taralli
      during storage.
AB  - Baking process leads to a huge quantity of newly formed volatile compounds, which
      play a major role in developing the flavor of the final product. The aim of this
      work was to investigate on the evolution of the volatile profile of taralli as a
      function of both the kind of oil used in the dough and the storage time. The
      volatile compounds from the taralli were extracted by headspace solid-phase
      microextraction and analyzed by gas-chromatography/mass spectrometry (GC/MS).
      Forty-four volatile compounds were identified in taralli, most of which produced
      by thermically induced reactions occurring during baking process, such as
      volatiles deriving from Maillard reaction and/or sugar degradation and lipid
      oxidation. The results obtained demonstrated the essential role played by the
      type of oil on the formation and on the release of volatile compounds. The
      volatile compounds significantly increased during storage and their individual
      levels were in most cases significantly lower in taralli made with extra virgin
      olive oil than in those made with refined oils. Finally, the taralli made with
      extra virgin olive oil, compared with those prepared with other vegetable oils,
      showed to be more resistant to oxidation, probably due to the presence of natural
      antioxidants.

PMID- 22384959
TI  - Effect of cocoa butter structure on oil migration.
AB  - Oil migration from a high oil content filling into adjacent chocolate causes
      changes in product quality. The objective of this study was to quantify the oil
      migration from a cream filling system into cocoa butter, which provided a model
      for the behavior of chocolate-enrobed confectionery products with a soft, creamy
      center. Magnetic resonance imaging (MRI) was used to monitor spatial and temporal
      changes of liquid lipid content. A multislice spin echo pulse sequence was used
      to acquire images with a 7.8 ms echo time and a 200 ms repetition time using a
      1.03 T Aspect Imaging MRI spectrometer. Samples were prepared as a 2-layer model
      system of cocoa butter and model cream filling. Three methods were used to
      prepare the cocoa butter: static, seeded, and sheared. Samples were stored at 25 
      degrees C for a time frame of 56 d. The rate of oil migration was quantified by a
      kinetic expression based on the linear dependence of oil uptake by cocoa butter
      and the square root of the time. Samples showed distinctly different rates of oil
      migration, as evidenced by quantitative differences in the kinetic rate constant.
      Practical Application:  This work will be helpful to elucidate the influence of
      crystallization process and structural properties such as crystal nanostructure
      and crystal habit on the migration of oil through a crystalline fat matrix.

PMID- 22384962
TI  - Effect of amino acids on red pigments and citrinin production in Monascus ruber.
AB  - Amino acids were used as sole nitrogen sources to examine their effects on the
      production of water-soluble red pigments and citrinin by Monascus ruber ATCC
      96218 cultivated on chemically defined media. In general, when glycine, tyrosine,
      arginine, serine, or histidine were used as sole nitrogen sources, they favored
      the production of red pigments, and restricted the synthesis of the mycotoxin. In
      contrast, the production of citrinin was enhanced in media supplemented with
      either glutamate, alanine, or proline. Histidine was found to be the most
      valuable amino acid as it resulted in the highest production of red pigments and
      almost completely eliminated the formation of mycotoxin.

PMID- 22384963
TI  - Temporal variation of microbiological and chemical quality of noncarbonated
      bottled drinking water sold in Sri Lanka.
AB  - Use of bottled water in Sri Lanka has increased over the last decade, while new
      brands of bottled water are often introduced to the market. However, the
      manufacturers' adherence to bottled water regulations is questionable, raising
      concerns regarding the quality of bottled water. The objective of the current
      study was to investigate the microbiological and chemical quality of bottled
      water in Sri Lanka. Thirty bottled water brands were sampled and their chemical
      and microbiological parameters were analyzed. Microbiological analysis was
      carried out within 1 to 3, 3 to 6, 6 to 9, and 9 to 12 mo after the date of
      manufacture. The results indicated that 63% of brands tested exceeded the levels
      permitted by the Sri Lanka Standards Institution (SLSI) for presumptive total
      coliforms (TC) (<10 cfu per 100 mL) whereas 97% brands exceeded the World Health
      Organization (WHO) permitted level. Thirty percent of brands exceeded the limit
      for presumptive fecal coliforms (FC) (0 cfu per 100 mL in accordance with WHO
      permitted levels, SLSI and the Sri Lanka Health Ministry requirement). Eighty
      percent of brands showed higher heterotrophic plate counts (HPC) which exceeded
      the WHO guidelines for bottled drinking water. Throughout their shelf life, the
      counts of TC, FC, and HPC bacteria decreased. Bacteria identified were Klebsiella
      pneumoniae ssp. pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, and
      Pasteurella haemolytica, the most frequently being P. aeruginosa. The dominant
      fungi identified were Aspergillus sp. and Penicillium sp. Inorganic chemical
      parameters were within permitted levels for all brands except for initial content
      of ammonia. The results of this study show the need for the bottling industry to
      be monitored closely by relevant authorities, in order to provide safe bottled
      drinking water to consumers in Sri Lanka.

PMID- 22384964
TI  - Cold plasma reduction of Salmonella and Escherichia coli O157:H7 on almonds using
      ambient pressure gases.
AB  - Contamination of raw nuts, including almonds, is a food safety concern. Cold
      plasma is a novel antimicrobial intervention that can eliminate foodborne
      pathogens. The objective of this work was to evaluate the efficacy of rapid cold
      plasma treatments in eliminating Salmonella and Escherichia coli O157:H7 from dry
      almonds. Three isolates of Salmonella (S. Anatum F4317, S. Stanley H0558, and S.
      Enteritidis PT30) and 3 isolates of E. coli O157:H7 (C9490, ATCC 35150, and ATCC
      43894) were separately grown and spot-inoculated (10 MUL) onto whole almonds and
      allowed to dry for 10 min. Inoculated almonds were treated with a cold plasma
      jet, with treatment variables evaluated in a factorial design for each isolate:
      time, distance, and feed gas. Treatment time was 0 s (control), 10 s, or 20 s.
      Distance from the emitter was 2, 4, or 6 cm. Feed gas was dry air or nitrogen.
      After treatment, the almonds were sampled using swabs. Survivors were enumerated
      on tryptic soy agar (TSA) plates. Cold plasma significantly reduced both
      pathogens on almonds. The greatest reduction observed was 1.34 log cfu/mL
      reduction of E. coli O157:H7 C9490 after 20 s treatment at 6 cm spacing. The
      interaction of treatment time with distance from plasma emitter head was complex,
      and isolate-dependent. Longer duration of treatment did not always result in
      enhanced reductions. In general, nitrogen as a feed gas resulted in a reduced
      antimicrobial efficacy compared to dry air. These results indicate that short
      pulses of atmospheric pressure cold plasma can significantly reduce Salmonella
      and E. coli O157:H7 on almonds.

PMID- 22384965
TI  - Effect of mannoproteins on the growth, gastrointestinal viability, and adherence
      to Caco-2 cells of lactic acid bacteria.
AB  - Yeast cell wall (YCW) preparations and yeast mannoprotein extracts have been
      effective against some enteropathogenic bacteria as Campylobacter jejuni,
      Escherichia coli, and Salmonella, and they can affect the population of
      beneficial lactic acid bacteria (LAB). In this work, we studied the effect of a
      mannoprotein extract on five strains of LAB. This extract was metabolised by the
      bacteria, enhancing their survival in simulated gastrointestinal juice, and
      increasing the adherence of Lactobacillus plantarum, L. salivarius, and
      Enterococcus faecium to Caco-2 cells. Yeast mannoproteins are promising naturally
      occurring compounds that could be used to enhance LAB intestinal populations and
      control pathogens.

PMID- 22384966
TI  - Determination of absolute threshold and just noticeable difference in the sensory
      perception of pungency.
AB  - Absolute threshold and just noticeable difference (JND) were determined for the
      perception of pungency using chili pepper in aqueous solutions. Absolute
      threshold and JND were determined using 2 alternative forced-choice sensory tests
      tests. High-performance liquid chromatography technique was used to determine
      capsaicinoids concentration in samples used for sensory analysis. Sensory
      absolute threshold was 0.050 mg capsaicinoids/kg sample. Five JND values were
      determined using 5 reference solutions with different capsaicinoids
      concentration. JND values changed proportionally as capsaicinoids concentration
      of the reference sample solutions changed. Weber fraction remained stable for the
      first 4 reference capsaicinoid solutions (0.05, 0.11, 0.13, and 0.17 mg/kg) but
      changed when the most concentrated reference capsaicinoids solution was used
      (0.23 mg/kg). Quantification limit for instrumental analysis was 1.512 mg/kg
      capsaicinoids. Sensory methods employed in this study proved to be more sensitive
      than instrumental methods. Practical Application: A better understanding of the
      process involved in the sensory perception of pungency is currently required
      because "hot" foods are becoming more popular in western cuisine. Absolute
      thresholds and differential thresholds are useful tools in the formulation and
      development of new food products. These parameters may help in defining how much
      chili pepper is required in a formulated product to ensure a perceptible level of
      pungency, as well as in deciding how much more chili pepper is required in a
      product to produce a perceptible increase in its pungency.

PMID- 22384967
TI  - Mechanisms for sensing fat in food in the mouth: Presented at the Symposium "The
      Taste for Fat: New Discoveries on the Role of Fat in Sensory Perception,
      Metabolism, Sensory Pleasure and Beyond" held at the Institute of Food
      Technologists 2011 Annual Meeting, New Orleans, LA, USA., June 12, 2011.
AB  - The brain areas that represent taste including the primary taste cortex and the
      orbitofrontal cortex also provide a representation of oral texture. Fat texture
      is represented by neurons independently of viscosity: some neurons respond to fat
      independently of viscosity, and other neurons encode viscosity. The neurons that
      respond to fat also respond to silicone and paraffin oil, indicating that the
      sensing is texture-specific not chemo-specific. This fat sensing is not related
      to free fatty acids such as linoleic acid, and a few other neurons that respond
      to free fatty acids typically do not respond to fat in the mouth. Complementary
      human functional neuroimaging studies show that the pleasantness of food texture
      is represented in the orbitofrontal cortex. These findings have implications for
      the design of foods that mimic the pleasant texture of fat in the mouth but have
      low energy content, and thus for the prevention and treatment of obesity.

PMID- 22384968
TI  - Genetic influences on oral fat perception and preference: Presented at the
      symposium "The Taste for Fat: New Discoveries on the Role of Fat in Sensory
      Perception, Metabolism, Sensory Pleasure and Beyond" held at the Institute of
      Food Technologists 2011 Annual Meeting, New Orleans, LA, June 12, 2011.
AB  - Research suggests that dietary fat is perceived not only by texture, but also by
      taste. However, the receptors for chemosensory response to fat have not been
      identified. We report on 2 genes,TAS2R38 and CD36, that may play a role in fat
      perception and preference in humans. TAS2R38 is a taste receptor for bitter
      thiourea compounds, including 6-n-propylthiouracil (PROP) and phenylthiocarbamide
      (PTC). Nontasters of these compounds tend to be poor at discriminating fat in
      foods, even though they prefer higher fat versions of these foods. CD36, a fatty
      acid translocase expressed on multiple cell types including taste cells, plays a
      critical role in fat preferences in animals. In studies conducted in our
      laboratory with African-American adults, we identified a variant in the CD36
      gene, rs1761667, that predicts oral responses to fat. Individuals who have the
      A/A genotype at this site tend to find Italian salad dressings creamier than
      those who have other genotypes at this site. In addition, A/A individuals report
      higher preferences for added fats, oils, and spreads (for example margarine).
      Assuming these data are confirmed in other populations, screening for CD36
      genotype may provide helpful information to food companies for developing fat
      modified products.

PMID- 22384969
TI  - Are free fatty acids effective taste stimuli in humans? Presented at the
      symposium "The Taste for Fat: New Discoveries on the Role of Fat in Sensory
      Perception, Metabolism, Sensory Pleasure and Beyond" held at the iNstitute of
      Food Technologists 2011 Annual Meeting, New Orleans, LA, June 12, 2011.
AB  - The popularity of low- and reduced-fat foods has increased as consumers seek to
      decrease their energy consumption. Fat replacers may be used in fat-reduced
      products to maintain their sensory properties. However, these ingredients have
      been largely formulated to replicate nongustatory properties of fats to foods and
      have only achieved moderate success. There is increasing evidence that fats also
      activate the taste system and uniquely evoke responses that may influence product
      acceptance. Work supporting a taste component of fat has prompted questions about
      whether fat constitutes an additional "primary" or "basic" taste quality. This
      review briefly summarizes this evidence, focusing on human studies, when
      possible. Effective stimuli, possible receptors, and physiological changes due to
      oral fat exposure are discussed. Some studies suggest that there are fatty acid
      tasters and nontasters and if verified could have implications for targeted
      product development.

PMID- 22384970
TI  - Ethics in publishing: what are some of the concerns?

PMID- 22384971
TI  - The taste for fat: new discoveries on the role of fat in sensory perception,
      metabolism, sensory pleasure, and beyond.

PMID- 22384972
TI  - Neuropsychological impairments on the NEPSY-II among children with FASD.
AB  - BACKGROUND: We examined the pattern of neuropsychological impairments of children
      with FASD (compared to controls) on NEPSY-II measures of attention and executive
      functioning, language, memory, visuospatial processing, and social perception.
      METHODS: Participants included 32 children with FASD and 30 typically developing
      control children, ranging in age from 6 to 16 years. Children were tested on the
      following subtests of the NEPSY-II: Attention and Executive Functioning (animal
      sorting, auditory attention/response set, and inhibition), Language
      (comprehension of instructions and speeded naming), Memory (memory for
      names/delayed memory for names), Visual-Spatial Processing (arrows), and Social
      Perception (theory of mind). Groups were compared using MANOVA. RESULTS: Children
      with FASD were impaired relative to controls on the following subtests: animal
      sorting, response set, inhibition (naming and switching conditions),
      comprehension of instructions, speeded naming, and memory for names total and
      delayed, but group differences were not significant on auditory attention,
      inhibition (inhibition condition), arrows, and theory of mind. Among the FASD
      group, IQ scores were not correlated with performance on the NEPSY-II subtests,
      and there were no significant differences between those with and without comorbid
      ADHD. CONCLUSIONS: The NEPSY-II is an effective and useful tool for measuring a
      variety of neuropsychological impairments among children with FASD. Children with
      FASD displayed a pattern of results with impairments (relative to controls) on
      measures of executive functioning (set shifting, concept formation, and
      inhibition), language, and memory, and relative strengths on measures of basic
      attention, visual spatial processing, and social perception.

PMID- 22384973
TI  - One-year clinical outcome of a randomized trial of polymer-free paclitaxel
      eluting stents versus biodegradable polymer-based rapamycin-eluting stents in
      patients with coronary heart disease.
AB  - BACKGROUND:  More widespread use of drug-eluting stents (DES) to treat coronary
      heart disease (CHD) has recently generated more attention to thrombosis, which
      was relative to the polymer. Polymer-free and biodegradable polymer-based stents
      are more frequently studied, but their efficacy on preventing detrimental
      clinical events is unclear. METHODS AND RESULTS: To assess whether polymer-free
      paclitaxel-eluting stent (YINYI stent) was noninferior or equivalent to
      biodegradable polymer-based rapamycin-eluting stents (EXCEL stent) in preventing
      detrimental clinical cardiovascular events, a total of 167 consecutive CHD
      patients requiring DES implantation were randomly divided into the YINYI group (n
      = 82) and the EXCEL group (n = 85). The primary end-point was major adverse
      cardiac events (MACE). The secondary end-points included stent thrombosis events,
      all-cause mortality, and rehospitalization. The study was designed to test the
      noninferiority or equivalence of the YINYI stent compared with the EXCEL stent
      with respect to one-year MACE according to a noninferiority or equivalence margin
      of 0.1. One-year MACE was 6.10% in the YINYI group versus 5.88% in the EXCEL
      group. The lower limit of the one-sided 95% confidence interval was -0.0582 (P =
      0.002 from the test for noninferiority). The 95% confidence interval for the
      equivalence test was [-0.0698, 0.0742] (P1 =0.004 and P2 =0.007 from 2 times the
      1-sided test for equivalence). There was no statistically significant difference
      in thrombosis events, all-cause death, and rehospitalization (all P > 0.05).
      CONCLUSIONS: In this small randomized trial, polymer-free paclitaxel-eluting
      stents appear to be noninferior or equivalent to biodegradable polymer-based
      rapamycin-eluting stents.

PMID- 22384974
TI  - The healing and spiritual properties of music therapy at a cancer care center.
AB  - BACKGROUND: This article explores the theme of spirituality, health, and well
      being, in relation to an emerging body of research on the impact of music therapy
      in cancer care. The focus of this article is a music therapy service established
      as part of a residential 5-day retreat program at a cancer care center. AIMS: The
      aim of the study was to explore the experiences of patients with cancer with one
      off group music therapy at a cancer care center. Central emphasis is given to
      exploring a range of themes relating to the healing and spiritual properties of
      music therapy group work. METHODS: This is a qualitative study, following a
      modified grounded-theory approach. Twenty-three (23) in-depth tape-recorded
      telephone interviews were conducted with people who had taken part in the music
      therapy sessions. RESULTS: The results focus on those findings relevant to
      notions of spirituality and healing, drawing on four overarching spirituality
      themes of transcendence, connectedness, search for meaning, and faith and hope.
      CONCLUSIONS: The authors consider the applicability of broader schemas that
      attempt to define and explore the role and significance of spirituality.

PMID- 22384975
TI  - Biological applications of dendrimers.

PMID- 22384976
TI  - The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and
      accumulation of ceramides in Candida albicans.
AB  - The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal
      glucosylceramides and induces apoptosis in Candida albicans. To further unravel
      the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a
      library of 2868 heterozygous C. albicans deletion mutants and identified 30
      RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes
      was involved in cell wall integrity and hyphal growth/septin ring formation.
      Consistent with these genetic data, we demonstrated that RsAFP2 interacts with
      the cell wall of C. albicans, which also contains glucosylceramides, and
      activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces
      mislocalization of septins and blocks the yeast-to-hypha transition in C.
      albicans. Increased ceramide levels have previously been shown to result in
      apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans
      membranes were analysed following RsAFP2 treatment and, as expected, increased
      accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans
      cells was detected. This is the first report on the interaction of a plant
      defensin with glucosylceramides in the fungal cell wall, causing cell wall
      stress, and on the effects of a defensin on septin localization and ceramide
      accumulation.

PMID- 22384977
TI  - Sensitive detection of proteins using assembled cascade fluorescent DNA nanotags
      based on rolling circle amplification.
AB  - A novel cascade fluorescence signal amplification strategy based on the rolling
      circle amplification (RCA)-aided assembly of fluorescent DNA nanotags as
      fluorescent labels and multiplex binding of the biotin-streptavidin system was
      proposed for detection of protein target at ultralow concentration. In the
      strategy, fluorescent DNA nanotags are prepared relying on intercalating dye
      arrays assembled on nanostructured DNA templates by intercalation between base
      pairs. The RCA product containing tandem-repeat sequences could serve as an
      excellent template for periodic assembly of fluorescent DNA nanotags, which were
      presented per protein recognition event to numerous fluorescent DNA nanotags for
      assay readout. Both the RCA and the multiplex binding system showed remarkable
      amplification efficiency, very little nonspecific adsorption, and low background
      signal. Using human IgG as a model protein, the designed strategy was
      successfully demonstrated for the ultrasensitive detection of protein target. The
      results revealed that the strategy exhibited a dynamic response to human IgG over
      a three-decade concentration range from 1.0 pM to 1.0 fM with a limit of
      detection as low as 0.9 fM. By comparison with the assay of multiple labeling
      antibodies with the dye/DNA conjugate, the limit of detection was improved by 4
      orders. The designed signal amplification strategy would hold great promise as a
      powerful tool to be applied for the ultrasensitive detection of target protein in
      immunoassay.

PMID- 22384978
TI  - Genome divergence during evolutionary diversification as revealed in replicate
      lake-stream stickleback population pairs.
AB  - Evolutionary diversification is often initiated by adaptive divergence between
      populations occupying ecologically distinct environments while still exchanging
      genes. The genetic foundations of this divergence process are largely unknown and
      are here explored through genome scans in multiple independent lake-stream
      population pairs of threespine stickleback. We find that across the pairs,
      overall genomic divergence is associated with the magnitude of divergence in
      phenotypes known to be under divergent selection. Along this same axis of
      increasing diversification, genomic divergence becomes increasingly biased
      towards the centre of chromosomes as opposed to the peripheries. We explain this
      pattern by within-chromosome variation in the physical extent of hitchhiking, as
      recombination is greatly reduced in chromosome centres. Correcting for this
      effect suggests that a great number of genes distributed widely across the genome
      are involved in the divergence into lake vs. stream habitats. Analyzing
      additional allopatric population pairs, however, reveals that strong divergence
      in some genomic regions has been driven by selection unrelated to lake-stream
      ecology. Our study highlights a major contribution of large-scale variation in
      recombination rate to generating heterogeneous genomic divergence and indicates
      that elucidating the genetic basis of adaptive divergence might be more
      challenging than currently recognized.

PMID- 22384979
TI  - Albuminuria independently predicts cardiovascular and all-cause mortality in a
      middle-aged and elderly Chinese population.
AB  - AIM: To investigate the relationship between albuminuria and mortality in a
      middle-aged-to-elderly Chinese population. METHODS: A total of 2,344 individuals
      aged over 40 in the same district were interviewed and followed up for 4 years.
      Information on survival or cause of death was recorded. A total of 2,181
      participants with detailed information were finally recruited. Baseline overnight
      urine samples were obtained to measure urinary albumin and creatinine. The
      urinary albumin excretion rate was expressed as albumin-to-creatinine ratio
      (ACR). Participants were divided into three groups, according to their ACR:
      normoalbuminuria (ACR < 30 mg/g), microalbuminuria (>= 30 - < 300 mg/g ACR) and
      macroalbuminuria (ACR >= 300 mg/g). The Cox proportional hazard model was used to
      analyze the relationships between albuminuria and cardiovascular and all-cause
      mortalities. RESULTS: Seventy-seven deaths with known causes were registered. The
      prevalences of microalbuminuria and macroalbuminuria at baseline were 8.3% and
      1.6%, respectively. Cardiovascular mortalities in the normoalbuminuria,
      microalbuminuria and macroalbuminuria groups were 2.4, 11.0, and 36.8/1,000
      person years (pyrs) respectively, and all-cause mortalities were 6.9, 20.6, and
      58.8/1,000 pyrs. After adjusting for confounding factors, the relative risks (RR)
      of cardiovascular mortality were 2.72 (95% CI, 1.06-4.20) in the microalbuminuria
      group, and 4.87 (95% CI, 2.46-9.45) in the macroalbuminuria group. Adjusted RRs
      for all-cause mortality were 2.01 (95% CI, 0.96-4.77) and 3.76 (95% CI, 1.52
      7.15) in the two groups, respectively. CONCLUSION: Albuminuria is a useful
      predictor of cardiovascular mortality and all-cause mortality in the general
      population.

PMID- 22384980
TI  - Pregnancy-associated plasma protein A (PAPP-A) and soluble receptor for advanced
      glycation end products (sRAGE)--intra- and inter-individual variability in
      chronic hemodialysis patients.
AB  - BACKGROUND: Dialysis patients are at high risk of cardiovascular complications.
      Pregnancy-associated plasma protein A (PAPP-A) as well as sRAGE (soluble receptor
      for advanced glycation end products) are new biomarkers related to cardiovascular
      disease. The aim of our study was to describe their intra- and inter-individual
      variability. METHODS: The studied group consisted of 21 chronic hemodialysis
      patients. PAPP-A, sRAGE and selected routine parameters were measured monthly
      during a 1-year prospective study. RESULTS: Our results show high intra
      individual variability of both PAPP-A and sRAGE. Both PAPP-A and sRAGE were
      closely linked to serum transferrin levels. Additionally, sRAGE was significantly
      associated with leukocyte count and haemoglobin. CONCLUSION: Our study
      demonstrates high intra-individual variability of PAPP-A and sRAGE in stable
      clinical status. This finding could be helpful for further evaluation of the
      significance of PAPP-A and sRAGE in chronic kidney disease.

PMID- 22384981
TI  - Do perceived high performance work systems influence the relationship between
      emotional labour, burnout and intention to leave? A study of Australian nurses.
AB  - AIMS: The purpose of this article was to explore the relationships between
      perceived high performance work systems, emotional labour, burnout and intention
      to leave among nurses in Australia. BACKGROUND: Previous studies show that
      emotional labour and burnout are associated with an increase in intention to
      leave of nurses. There is evidence that high performance work systems are in
      association with a decrease in turnover. There are no previous studies that
      examine the relationship between high performance work systems and emotional
      labour. DESIGN: A cross-sectional, correlational survey. METHODS: The study was
      conducted in Australia in 2008 with 183 nurses. Three hypotheses were tested with
      validated measures of emotional labour, burnout, intention to leave, and
      perceived high performance work systems. Principal component analysis was used to
      examine the structure of the measures. The mediation hypothesis was tested using
      Baron and Kenny's procedure and the moderation hypothesis was tested using
      hierarchical regression and the product-term. RESULTS: Emotional labour is
      positively associated with both burnout and intention to leave. Burnout mediates
      the relationship between emotional labour and intention to leave. Perceived high
      performance work systems negatively moderates the relationship between emotional
      labour and burnout. Perceived high performance work systems not only reduces the
      strength of the negative effect of emotional labour on burnout but also has a
      unique negative effect on intention to leave. CONCLUSION: Ensuring effective
      human resource management practice through the implementation of high performance
      work systems may reduce the burnout associated with emotional labour. This may
      assist healthcare organizations to reduce nurse turnover.

PMID- 22384982
TI  - Reasoning heuristics across the psychosis continuum: the contribution of
      hypersalient evidence-hypothesis matches.
AB  - INTRODUCTION: Hypersalience of evidence-hypothesis matches has recently been
      proposed as the cognitive mechanism responsible for the cognitive biases which,
      in turn, may contribute to the formation and maintenance of delusions. However,
      the construct lacks empirical support. The current paper investigates the
      possibility that individuals with delusions are hypersalient to evidence
      hypothesis matches using a series of cognitive tasks designed to elicit the
      representativeness and availability reasoning heuristics. It was hypothesised
      that hypersalience of evidence-hypothesis matches may increase a person's
      propensity to rely on judgements of representativeness (i.e., when the
      probability of an outcome is based on its similarity with its parent population)
      and availability (i.e., estimates of frequency based on the ease with which
      relevant events come to mind). METHODS: A total of 75 participants (25 diagnosed
      with schizophrenia with a history of delusions; 25 nonclinical delusion-prone; 25
      nondelusion-prone controls) completed four heuristics tasks based on the original
      Tversky and Kahnemann experiments. These included two representativeness tasks
      ("coin-toss" random sequence task; "lawyer-engineer" base-rates task) and two
      availability tasks ("famous-names" and "letter-frequency" tasks). RESULTS: The
      results across these four heuristics tasks showed that participants with
      schizophrenia were more susceptible than nonclinical groups to both the
      representativeness and availability reasoning heuristics. CONCLUSIONS: These
      results suggest that delusional ideation is linked to a hypersalience of evidence
      hypothesis matches. The theoretical implications of this cognitive mechanism on
      the formation and maintenance of delusions are discussed.

PMID- 22384983
TI  - Adjunctive usage of a non-comedogenic moisturizer with adapalene gel 0.1%
      improves local tolerance: a randomized, investigator-blinded, split-face study in
      healthy Asian subjects.
AB  - BACKGROUND: Adapalene gel 0.1% is an efficacious treatment for acne vulgaris in
      Asians. It is generally well tolerated, but may still cause cutaneous side
      effects among patients with sensitive skin. OBJECTIVE: To assess the ability of a
      moisturizing lotion (Cetaphil(r)) in improving the local tolerance of adapalene.
      METHODS: In this 4-week, randomized, investigator-blinded, split-face study among
      30 healthy volunteers of Chinese origin, adapalene gel was applied once daily to
      the whole face and the moisturizing lotion was applied once daily to only one
      side of the face according to the randomization scheme. RESULTS: At each study
      visit, both investigators and subjects reported better tolerance on the side of
      moisturizing lotion + adapalene gel than the side of adapalene gel only, with
      significant differences reported by the subjects during the first 2 weeks (p =
      0.039 and 0.013, respectively). Global worst score, defined as the average of
      worst scores for erythema, desquamation, dryness, stinging/burning and pruritus,
      was significantly lower for the side of moisturizing lotion + adapalene gel than
      for the side of adapalene gel alone (0.43 +/- 0.34 vs. 0.59 +/- 0.44, p = 0.032).
      CONCLUSION: The adjunctive usage of an effective moisturizer improves local
      tolerance of adapalene gel and may contribute to better adherence.

PMID- 22384984
TI  - Term stillbirth in older women.
AB  - Increasing numbers of women are choosing to delay pregnancy. Pregnancy in older
      women is associated with increased risks, of which stillbirth is one of the most
      devastating. This retrospective cohort study reviewed the obstetric outcomes in
      women aged 40 and above over an 11-year period to determine whether maternal age
      is an independent risk factor for term stillbirth. The study shows that advanced
      maternal age is an independent risk factor for term stillbirth (odds ratio 2.42,
      95% confidence interval 1.04-5.62).

PMID- 22384985
TI  - Erythrolic acids A-E, meroterpenoids from a marine-derived Erythrobacter sp.
AB  - Erythrolic acids A-E (1-5) are five unusual meroterpenoids isolated from the
      bacterium Erythrobacter sp. derived from a marine sediment sample collected in
      Galveston, TX. The structures were elucidated by means of detailed spectroscopic
      analysis and chemical derivatization. The erythrolic acids contain a 4
      hydroxybenzoic acid appended with a modified terpene side chain. The side-chain
      modifications include oxidation of a terminal methyl substituent and in the case
      of 1-4 addition of a two-carbon unit to give terpene side chains of unusual
      length: C22 for 1 and 2, C17 for 3, and C12 for 4. The relative and absolute
      configurations of the meroterpenoids were determined by coupling constant, NOE,
      and Mosher's analysis. In vitro cytotoxicity toward a number of nonsmall cell
      lung cancer (NSCLC) cell lines revealed only modest activity for erythrolic acid
      D (4) (2.5 MUM against HCC44). The discovery of these unusual diterpenes, along
      with the previously reported erythrazoles, demonstrates the natural product
      potential of a previously unstudied group of bacteria for drug discovery. The
      unusual nature of the terpene side chain, we believe, involves an oxidation of a
      terminal methyl group to a carboxylic acid and subsequent Claisen condensation
      with acetyl-CoA.

PMID- 22384986
TI  - Treatment options for active removal of renal stones.
AB  - This study provides an update on the technological aspects of the methods for
      active removal of renal stones. Currently, extracorporeal shock wave lithotripsy
      (ESWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are the
      available options. Findings are based upon recent literature from the PubMed
      database and the European Association of Urology (EAU) guidelines. ESWL remains
      the option of choice for stones with diameter <= 20 mm due to its low invasive
      character, whereas PCNL is the standard for stones with diameter > 20 mm because
      of its high stone-free rates. Although ESWL treatment has become more patient
      friendly, its efficacy has not improved. On the other hand, URS has gained
      renewed interest due to new technological developments and improved treatment
      methods.

PMID- 22384987
TI  - Spatial and temporal variation in evacuee risk perception throughout the
      evacuation and return-entry process.
AB  - Developing effective evacuation and return-entry plans requires understanding the
      spatial and temporal dimensions of risk perception experienced by evacuees
      throughout a disaster event. Using data gathered from the 2008 Cedar Rapids, Iowa
      Flood, this article explores how risk perception and location influence evacuee
      behavior during the evacuation and return-entry process. Three themes are
      discussed: (1) the spatial and temporal characteristics of risk perception
      throughout the evacuation and return-entry process, (2) the relationship between
      risk perception and household compliance with return-entry orders, and (3) the
      role social influences have on the timing of the return by households. The
      results indicate that geographic location and spatial variation of risk
      influenced household risk perception and compliance with return-entry plans. In
      addition, sociodemographic characteristics influenced the timing and
      characteristics of the return groups. The findings of this study advance
      knowledge of evacuee behavior throughout a disaster and can inform strategies
      used by emergency managers throughout the evacuation and return-entry process.

PMID- 22384988
TI  - Prolonged elevation of serum granulysin in drug-induced hypersensitivity
      syndrome.

PMID- 22384989
TI  - Legitimising and rationalising in talk about satisfaction with formal healthcare
      among bereaved family members.
AB  - While there is a fair amount of knowledge regarding substantive features of end
      of life care that family members desire and appreciate, we lack full
      understanding of the process whereby family members formulate care evaluations.
      In this article we draw on an analysis of interview data from 24 bereaved family
      members to explicate how they interpret their experiences and formulate
      evaluations of end of life care services. Most participants wove between
      expressing and legitimising dissatisfaction, and qualifying or diffusing it. This
      occurred through processes of comparisons against prior care experiences and
      expectations, personalising (drawing on personal situations and knowledge),
      collectivising (drawing on conversations with and observations of others) and
      attempting to understand causes for their negative care experiences and to
      attribute responsibility. The findings suggest that dissatisfaction might be
      diffused even where care is experienced negatively, primarily through the
      acknowledgement of mitigating circumstances. To a lesser extent, some
      participants attributed responsibility to the 'system' (policy and decision
      makers) and individual staff members. The findings are discussed in relation to
      the theoretical understanding of satisfaction and evaluation processes and how
      satisfaction data might inform improvements to care quality.

PMID- 22384991
TI  - Tropical neurology.

PMID- 22384990
TI  - Native intact mass determination of antibodies conjugated with monomethyl
      Auristatin E and F at interchain cysteine residues.
AB  - We present here a method for the rapid determination of the intact mass of
      noncovalently associated antibody heavy chains (HC) and light chains (LC) which
      result from the attachment of drug conjugates to interchain cysteine residues. By
      analyzing the antibody-drug conjugate (ADC) using native desalting conditions, we
      maintain the intact bivalent structure of the ADC, which ordinarily would
      decompose as a consequence of denaturing chromatographic conditions typically
      used for liquid chromatographic-mass spectrometric (LC-MS) analysis. The mass of
      the desalted ADC is subsequently determined using standard desolvation and
      ionization conditions. Methods presented previously in the literature for
      analyzing interchain cysteinyl-linked ADCs are either not amenable to online mass
      spectrometry or result in the denaturing dissociation of conjugated HC and LC
      during chromatographic separation and subsequent mass measurement. We have
      avoided this outcome with our method and have successfully and routinely obtained
      intact mass measurement of IgG1 mAbs conjugated with maleimidocaproyl-monomethyl
      Auristatin F (mcMMAF) and valine-citrulline-monomethyl Auristatin E (vcMMAE) at
      interchain cysteine residues. Our results thus represent the first reported
      direct measurement of the intact mass of an ADC conjugated at interchain cysteine
      residues.

PMID- 22384992
TI  - Tuberculosis infections of the central nervous system.
AB  - The causative agent of Tuberculosis meningitis is Mycobacterium tuberculosis,
      which is the bacteria that causes pulmonary tuberculosis. Proliferating into the
      central nervous system occurs from other sites of infection within the body.
      Brain damage can result from the infection that may lead to abnormal behavior,
      mental impairments, motor type paralysis, and seizures. Tuberculosis infections
      of the central nervous system are a serious and often fatal disease predominantly
      impacting young children, and is thought to be the most devastating form of the
      disease. Isoniazid is the only first line bactericidal agent that easily crosses
      the blood-brain barrier and achieves concentrations in cerebrospinal fluid
      similar to those in serum. Rifampicin, ethambutol, and streptomycin all penetrate
      into the cerebrospinal fluid poorly, and even in the setting of meningeal
      inflammation. As much as one-third of the current world's population may be
      infected with tuberculosis. Tuberculosis infection of the central nervous system
      is a serious type of extrapulmonary proliferation of this disease . In developing
      countries, it has high predominance in children. Pathological manifestations of
      cerebral tuberculosis occur, of which the most common is tuberculous meningitis,
      followed by tuberculoma, tuberculous abscess, cerebral miliary tuberculosis,
      tuberculous encephalopathy, tuberculous encephalitis, and tuberculous arteritis.
      Brain abscesses of Mycobacterium tuberculosis can induce seizures and coma
      leading to death and complicated due to multiorgan failure. Rapid diagnosis and
      early intervention is vital for successful outcome for patients. Further studies
      are required to understand the proliferation of tuberculosis meningitis in
      addition to the elucidation of new therapeutic drugs for the successful clinical
      treatment of this deadly disease.

PMID- 22384993
TI  - Impact of skill mix variations on patient outcomes following implementation of
      nursing hours per patient day staffing: a retrospective study.
AB  - AIMS: This article is a report of a study of the association between skill mix
      and 14 nursing-sensitive outcomes following implementation of the nursing hours
      per patient day staffing method in Western Australian public hospitals in 2002,
      which determined nursing hours by ward category but not skill mix. BACKGROUND:
      Findings from previous studies indicate that higher nurse staffing levels and a
      richer skill mix are associated with improved patient outcomes. Measuring skill
      mix at a hospital level for specific staffing methods and associated nursing
      sensitive patient outcomes are important in providing staffing for optimal
      patient care. DESIGN: The research design for the larger study was
      retrospectively analysing patient and staffing administrative data from three
      adult tertiary hospitals in metropolitan Perth over 4 years. METHODS: A subset of
      data was used to determine the impact of skill mix on nursing-sensitive outcomes
      following implementation of the staffing method. All patient records (N=103,330)
      and nurse staffing records (N=73,770) from nursing hours per patient day wards
      from October 2002-June 2004 following implementation were included. RESULTS:
      Increases in Registered Nurse hours were associated with important decreases in
      eight nursing-sensitive outcomes at hospital level and increases in three nursing
      sensitive outcomes. The lowest skill mix saw the greatest reduction in nursing
      sensitive outcome rates. CONCLUSIONS: The skill mix of nurses providing care
      could impact patient outcomes and is an important consideration in strategies to
      improve nurse staffing. Levels of hospital nurse staffing and skill mix are
      important organizational characteristics when predicting patient outcomes.

PMID- 22384997
TI  - A rationale for a clinical supervision database for mental health nursing in the
      UK.
AB  - Clinical supervision (CS) is regarded as a valuable resource for mental health
      nursing. While there is considerable anecdotal reports of its implementation
      throughout the UK, these attempts are not without difficulty. A common tension
      reported in the literature relates to its provision being more akin to managerial
      supervision within a line-management hierarchy which jars with its original
      intention and spirit. This paper will provide a discussion on the implementation
      of CS in mental health nursing in the UK, beginning with its suggested importance
      for the discipline. Following on from this, the rationale for a CS database and
      description of one NHS Board's attempts at developing a resource, initially
      focusing on clinical supervisors of psychological therapies, will be presented.

PMID- 22384998
TI  - Developmental incompetence to stand trial in juvenile courts.
AB  - Juveniles' competency to participate in delinquency proceedings has received
      increased attention in recent years. Developmental incompetence, whereby
      juveniles' incompetency is based upon their immaturity, as opposed to a mental
      disorder or developmental disability, is an evolving and important aspect of this
      area of law. The following paper reviews theories used to support the notion of
      developmental incompetence, as well as the extant empirical research on
      juveniles' competency-related abilities. Using a LexisNexis search, statutory and
      case laws pertaining to juvenile competency were identified across the 50 states
      and the District of Columbia. Only six states clearly allow developmental
      incompetence, whereas 17 have laws that do not include developmental immaturity
      as an acceptable basis of incompetence in juvenile courts. Developmental
      incompetence is likely to affect a relatively small proportion of juvenile cases,
      but has important implications for juvenile forensic practice. Recommendations
      are offered for forensic practitioners conducting this type of evaluation.

PMID- 22384999
TI  - Trial-to-trial correlation between thalamic sensory response and global EEG
      activity.
AB  - Thalamic gating of sensory inputs to the cortex varies with behavioral
      conditions, such as sleep-wake cycles, or with different stages of anesthesia.
      Behavioral conditions in turn are accompanied by stereotypic spectral content of
      the EEG. In the rodent somatosensory system, the receptive field size of the
      ventral posteromedial thalamic nucleus (VPM) shrinks when anesthesia is deepened.
      Here we examined whether evoked thalamic responses are correlated with global EEG
      activity on a fine time scale of a few seconds. Trial-by-trial analysis of
      responses of VPM cells to whisker stimulation in lightly anesthetized rats
      indicated that increased EEG power in the delta band (1-4 Hz) was accompanied by
      a small, but highly significant, reduction in spontaneous and evoked thalamic
      firing. The opposite effect was found for the gamma EEG band (30-50 Hz). These
      significant correlations were not accompanied by an apparent change in the size
      of the receptive fields and were not EEG phase-related. The correlation between
      EEG and firing rate was observed only in neurons that responded to multiple
      whiskers and was higher for the non-principal whiskers. Importantly, the
      contributions of the two EEG bands to the modulation of VPM responses were to a
      large extent independent of each other. Our findings suggest that information
      conveyed by different whiskers can be rapidly modulated according to the global
      brain activity.

PMID- 22385000
TI  - New Zealand kanuka honey has high levels of methylglyoxal and antimicrobial
      activity.

PMID- 22385001
TI  - Relative risk perception for terrorism: implications for preparedness and risk
      communication.
AB  - Terrorism presents a significant risk that is often approached at public policy,
      infrastructure, or emergency management level. Public perceptions of the
      likelihood of terrorist events, and how this may relate to individual
      preparedness, are not always extensively examined. The tendency to think that
      negative events are less likely to happen to oneself than to the average person
      is known as optimism bias. Optimism bias is relevant to perceptions of terrorism,
      because it is thought to be related to a reduction in precaution use. Using an
      online survey of 164 participants, this study aimed to determine whether Sydney
      residents thought they had a lower likelihood of experiencing terrorist events
      than other Australians. Significant optimism bias was observed for witnessing
      terrorist events, but not for personally experiencing terrorist events. In
      addition, Sydney residents tended to think that terrorist attacks were more
      likely to occur in Sydney than another major Australian city in the next five
      years. At the same time, household and workplace preparedness for terrorism was
      quite low, as was awareness of emergency strategies in the central business
      district. Perceptions of high likelihood of terrorism happening in one's own
      city, yet low preparedness present a challenge for risk communication and
      emergency management strategies. The diversity of possible terrorist targets, and
      the simple plans that can moderate the effects of a disaster may need to be
      emphasized in future anti-terrorism initiatives.

PMID- 22385002
TI  - Subarachnoid hemorrhage in a case of segmental arterial mediolysis with
      coexisting intracranial and intraabdominal aneurysms.
AB  - The authors report the rare case of a 58-year-old man with segmental arterial
      mediolysis (SAM) with associated intracranial and intraabdominal aneurysms, who
      suffered subarachnoid hemorrhage (SAH) due to rupture of an intracranial
      aneurysm. This disease primarily involves the intraabdominal arterial system,
      resulting in intraabdominal and retroperitoneal hemorrhage in most cases. The
      patient presented with severe headache and vomiting. The CT scans of the head
      revealed SAH. Cerebral angiography revealed 3 aneurysms: 1 in the right distal
      anterior cerebral artery (ACA), 1 in the distal portion of the A(1) segment of
      the right ACA, and 1 in the left vertebral artery. The patient had a history of
      multiple intraabdominal aneurysms involving the splenic, gastroepiploic,
      gastroduodenal, and bilateral renal arteries. He underwent a right frontotemporal
      craniotomy and fibrin coating of the dissecting aneurysm in the distal portion of
      the A(1) segment of the right ACA, which was the cause of the hemorrhage. Follow
      up revealed no significant changes in the residual intracranial and
      intraabdominal aneurysms. An SAH due to SAM with associated multiple
      intraabdominal aneurysms is extremely rare. The authors describe their particular
      case and review the literature pertaining to SAM with associated intracranial and
      intraabdominal aneurysms.

PMID- 22385003
TI  - Glioblastoma resection.

PMID- 22385004
TI  - Glioblastoma resection.

PMID- 22385005
TI  - The effect of targeted agents on outcomes in patients with brain metastases from
      renal cell carcinoma treated with Gamma Knife surgery.
AB  - OBJECT: Gamma Knife surgery (GKS) has been reported as an effective modality for
      treating brain metastases from renal cell carcinoma (RCC). The authors aimed to
      determine if targeted agents such as tyrosine kinase inhibitors, mammalian target
      of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC
      after GKS. METHODS: Between 1999 and 2010, 61 patients with brain metastases from
      RCC were treated with GKS. A median dose of 20 Gy (range 13-24 Gy) was prescribed
      to the margin of each metastasis. Kaplan-Meier analysis was used to determine
      local control, distant failure, and overall survival rates. Cox proportional
      hazard regression was performed to determine the association between disease
      related factors and survival. RESULTS: Overall survival at 1, 2, and 3 years was
      38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years
      was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3
      years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died
      of neurological disease. The median survival for patients receiving targeted
      agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not
      receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was
      93% versus 60% for patients receiving and those not receiving targeted agents,
      respectively (p = 0.01). Multivariate analysis showed that the use of targeted
      agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for
      improved survival. Two patients experienced post-GKS hemorrhage within the
      treated volume. CONCLUSIONS: Targeted agents appear to improve local control and
      overall survival in patients treated with GKS for metastastic RCC.

PMID- 22385006
TI  - Permanent anosmia and ageusia after resection of a left temporoinsular low-grade
      glioma: anatomofunctional considerations.
AB  - Five percent of the general population has olfactory or gustatory disorders,
      although most do not complain about it. However, in some cases, these symptoms
      can be disabling and may affect quality of life. Anosmia was reported as a
      possible complication following head injury and neurosurgical procedures,
      particularly after the resection of tumors located in the anterior fossa and the
      treatment of aneurysms in the anterior circulation. Nonetheless, in all of these
      situations, olfactory dysfunction could be explained by damage to the peripheral
      olfactory system.   Here, the authors report a case of complete anosmia
      associated with ageusia following awake resection of a low-grade glioma involving
      the left temporoinsular region, with no recovery during a follow-up of 3 years.
      The frontal lobe was not retracted, and the olfactory tract was not visualized
      during surgery; therefore, postoperative anosmia and ageusia are likely explained
      by damage to the cortex and central pathways responsible for these senses. The
      authors suggest that the patient might have had a subclinical right hemianosmia
      before surgery, which is a common condition. After resection of the central
      structures critical for smell and taste processing in the left hemisphere, the
      patient could have finally had bilateral and complete olfactory and gustatory
      loss.   This is the first known report of permanent anosmia and ageusia following
      glioma surgery. Because these symptoms might have been underestimated, more
      attention should be devoted to olfaction and taste, especially with regard to
      possible subclinical preoperative deficit.

PMID- 22385007
TI  - Glioblastoma resection.

PMID- 22385008
TI  - Formation of rectangular packing and one-dimensional lines of C60 on 11
      phenoxyundecanethiol self-assembled monolayers on Au(111).
AB  - The behavior of C(60) molecules deposited onto 11-phenoxyundecanethiol (phenoxy)
      self-assembled monolayers (SAMs) is studied using ultrahigh vacuum scanning
      tunneling microscopy (UHV-STM) and spectroscopy. We observe that after thermally
      annealing between 350 and 400 K in vacuum a combination of hexagonally close
      packed islands, rectangularly packed islands, and isolated single lines of C(60)
      is observed when the C(60) is initially deposited on an unannealed phenoxy SAM.
      However, only rectangularly packed islands are found when they are deposited on a
      preannealed phenoxy SAM. We determine the rectangular packing to have a (2?3 * 4)
      rectangular unit cell with respect to the underlying Au(111) substrate. This type
      of C(60) structure has not been observed previously for multicomponent self
      assemblies on a surface. We discuss the possible causes for the formation of this
      structure as well as the differences between starting on an unannealed SAM and an
      annealed one. This study demonstrates the capability of functionalized
      alkanethiol SAMs to control the growth and structure of C(60) islands during
      annealing depending on the structural changes of the SAM itself; by preannealing
      the SAM, the motion of the C(60) can be confined and unique structures resulting
      from interactions between the SAM molecules and C(60) can be produced.

PMID- 22385009
TI  - Nonsense beta-thalassemia mutation at codon 37 (TGG>TGA), detected for the first
      time in three Turkish cases.
AB  - Thalassemias are genetically heterogeneous group of disorders with reduced or
      absent production of globin. beta-Thalassemia major can be caused by homozygosity
      or compound heterozygosity for beta-globin gene mutation. Here we report, for the
      first time in Turkey, three cases who carry the nonsense beta-thalassemia (beta
      thal) mutation at codon 37 (TGG>TGA; Trp->Stop) causing premature stop codon.

PMID- 22385010
TI  - Bayesian influence measures for joint models for longitudinal and survival data.
AB  - This article develops a variety of influence measures for carrying out
      perturbation (or sensitivity) analysis to joint models of longitudinal and
      survival data (JMLS) in Bayesian analysis. A perturbation model is introduced to
      characterize individual and global perturbations to the three components of a
      Bayesian model, including the data points, the prior distribution, and the
      sampling distribution. Local influence measures are proposed to quantify the
      degree of these perturbations to the JMLS. The proposed methods allow the
      detection of outliers or influential observations and the assessment of the
      sensitivity of inferences to various unverifiable assumptions on the Bayesian
      analysis of JMLS. Simulation studies and a real data set are used to highlight
      the broad spectrum of applications for our Bayesian influence methods.

PMID- 22385011
TI  - Respiratory viral infections during the first 28 days after transplantation in
      pediatric hematopoietic stem cell transplant recipients.
AB  - Respiratory viruses (RVs) are a known cause of morbidity and mortality after
      hematopoietic stem cell transplantation (HSCT). In this retrospective study, we
      focused on the first 28 d after transplantation in pediatric HSCT recipients and
      showed that a multiplex PCR assay significantly increased RV detection compared
      with a viral culture method. Among 176 pediatric HSCT recipients, 84 with
      respiratory symptoms within one yr after HSCT were tested by viral culture or
      multiplex PCR. Within 28 d after HSCT, nine patients were infected with RVs; the
      incidence of a first episode of RV infection within 28 d after HSCT was 5.1%.
      Eight patients recovered without complications. However, one patient died of
      adenovirus (AdV) pneumonia with pulmonary hemorrhage; the mortality rate of RV
      infection within 28 d after HSCT was 0.57%. In the nine patients with RV
      infection, five different types of RV were identified, either alone or with
      another RV. These were corona virus (CoV), rhinovirus (RhV) and respiratory
      syncytial virus combined with CoV; AdV combined with RhV; and parainfluenza
      virus. Viral culture detected only one case of RV infection, while multiplex PCR
      detected eight, suggesting that screening of respiratory infections using
      multiplex PCR is better than the conventional culture method.

PMID- 22385012
TI  - A critical review of the literature on NLD as a developmental disorder.
AB  - The extant research on nonverbal learning disability (NLD) was analyzed in this
      review. Studies were defined for use in the review as those that appeared in a
      peer-reviewed journal and included participants characterized as having NLD. Each
      study also needed to provide a statistical analysis of dependent variables. An a
      priori system was used to evaluate the quality of the research. Of the 88
      publications found, 32 met criteria for inclusion in the review, with 6 meeting
      full criteria as strong studies. The diagnostic criteria used and the research
      findings are briefly discussed, as are proposed guidelines for future research.

PMID- 22385013
TI  - Defining dosing pattern characteristics of successful tapers following methadone
      maintenance treatment: results from a population-based retrospective cohort
      study.
AB  - AIMS: To identify dose-tapering strategies associated with sustained success
      following methadone maintenance treatment (MMT). DESIGN: Population-based
      retrospective cohort study. SETTING: Linked administrative medication
      dispensation data from British Columbia, Canada. PARTICIPANTS: From 25 545
      completed MMT episodes, 14 602 of which initiated a taper, 4183 individuals
      (accounting for 4917 MMT episodes) from 1996 to 2006 met study inclusion
      criteria. MEASUREMENTS: The primary outcome was sustained successful taper,
      defined as a daily dose <=5 mg per day in the final week of the treatment episode
      and no treatment re-entry, opioid-related hospitalization or mortality within 18
      months following episode completion. FINDINGS: The overall rate of sustained
      success was 13% among episodes meeting inclusion criteria (646 of 4917), 4.4%
      (646 of 14 602) among all episodes initiating a taper and 2.5% (646 of 25 545)
      among all completed episodes in the data set. The results of our multivariate
      logistic regression analyses suggested that longer tapers had substantially
      higher odds of success [12-52 weeks versus <12 weeks: odds ratio (OR): 3.58; 95%
      confidence interval (CI): 2.76-4.65; >52 weeks versus <12 weeks: OR: 6.68; 95%
      CI: 5.13-8.70], regardless of how early in the treatment episode the taper was
      initiated, and a more gradual, stepped tapering schedule, with dose decreases
      scheduled in only 25-50% of the weeks of the taper, provided the highest odds of
      sustained success (versus <25%: OR: 1.61; 95% CI: 1.22-2.14). CONCLUSIONS: The
      majority of patients attempting to taper from methadone maintenance treatment
      will not succeed. Success is enhanced by gradual dose reductions interspersed
      with periods of stabilization. These results can inform the development of a more
      refined guideline for future clinical practice.

PMID- 22385014
TI  - Diagnostic accuracy of focused assessment with sonography for trauma (FAST)
      examinations performed by emergency medical technicians.
AB  - OBJECTIVE: We aimed to assess the diagnostic accuracy of focused assessment with
      sonography for trauma (FAST) examinations when used by emergency medical
      technicians (EMTs) to detect the presence of free abdominal fluid. METHODS: Six
      level 1 EMTs (similar to intermediate EMTs in the United States) who worked at a
      tertiary emergency department in Korea underwent an educational program
      consisting of two one-hour didactic lectures that included the principles of
      ultrasonography, the anatomy of the abdomen, and two hours of hands-on practice.
      After this educational session, the EMTs performed FAST examinations on a
      convenience sample of patients from July 1 to October 5, 2009. These patients
      also received an abdominal computed tomography (CT) scan regardless of their
      chief complaints. The CT findings served as the definitive standard and were
      interpreted routinely and independently by emergency radiologists who were
      blinded to the study protocol. In addition, the EMTs were blinded to the CT
      findings. A positive CT finding was defined as the presence of free fluid, as
      interpreted by the radiologist. The sensitivity, specificity, predictive values,
      and their 95% confidence intervals (CIs) were calculated. Informed consent was
      obtained from all participating patients. RESULTS: Among the 1,060 eligible
      patients with abdominal CT scans, 403 patients were asked to participate in the
      study, and 240 patients agreed. Of these 240 patients, 80 (33.3%) had results
      showing the presence of free fluid. Fourteen patients had a significant amount of
      peritoneal cavity fluid, 15 had a moderate amount of peritoneal cavity fluid, and
      51 had a minimal amount of peritoneal cavity fluid. Compared with the CT
      findings, the diagnostic performance of the FAST examination had a sensitivity of
      61.3% (95% CI, 50.3%-71.2%), specificity of 96.3% (95% CI, 92.1%-98.3%), positive
      predictive value of 89.1% (95% CI, 77.0%-95.4%), and negative predictive value of
      83.2% (95% CI, 76.9%-88.2%). For a significant or moderate amount of peritoneal
      cavity fluid, the sensitivity was considerably higher (86.2%). CONCLUSION: EMTs
      in Korea showed a high diagnostic performance that was comparable to that of
      surgeons and physicians when detecting peritoneal cavity free fluid in a Korean
      emergency department setting. The validity of FAST examinations in prehospital
      care situations should be investigated further.

PMID- 22385015
TI  - Synthesis of imidazo[4,5-c]pyrazoles via copper-catalyzed amidine cyclization.
AB  - A new synthetic approach to 4-substituted imidazo[4,5-c]pyrazoles is proposed on
      the basis of the N'-(4-halopyrazol-5-yl)amidine cyclization under the conditions
      of copper-catalyzed cross-coupling reactions. Using 5-aminopyrazoles and copper
      catalysts as starting materials, the method is inexpensive and convenient and
      allows a wide range of substituents at all positions of the imidazo[4,5
      c]pyrazole nucleus.

PMID- 22385016
TI  - DLQI and CDLQI scores should not be combined.

PMID- 22385017
TI  - Miltefosine: a novel treatment option for mast cell-mediated diseases.
AB  - Mast cell-mediated diseases such as urticaria, mastocytosis and atopic dermatitis
      are common, disabling and hard to treat. Recently, the lipid raft modulator
      miltefosine has been shown to inhibit mast cell activation in vitro and in vivo.
      Moreover, three randomized and placebo-controlled trials have assessed the
      effects of miltefosine in mast cell-driven conditions. Here, we review the
      experimental and clinical evidence in support of miltefosine as a novel treatment
      option for mast cell-mediated diseases and we discuss the most imminent questions
      and issues that need to be addressed by future research and clinical trials.

PMID- 22385018
TI  - Free radicals identification from the complex EPR signals by applying higher
      order statistics.
AB  - EPR spin-trapping technique, using spin-trap DEPMPO, has been shown to be capable
      of simultaneous detection of multiple free radical species which are generated in
      the same system. However, such approach proved to be unsuitable due to the
      complexity of the obtained composite EPR signal of the spin-adducts. Although
      rather unique, each individual spin-adduct signal is composed of at least eight
      EPR peaks, thus many of them could be overlapped, making the signal separation
      process almost impossible to accomplish by using ordinary chemometrics methods
      such as fast independent component analysis (FastICA), factor analysis (FA), or
      parallel factor analysis (PARAFAC). We have proposed a new approach which
      involves cumulative usage of two different statistical techniques. Applied
      algorithms are based on the second order statistics, second order blind
      identification with the robust orthogonalization algorithm (SOBI-RO), and the
      constrained independent component analysis (CICA).

PMID- 22385019
TI  - Clinical comparison of ICD detection algorithms that include rapid-VT zones.
AB  - INTRODUCTION: The safe use of antitachycardia pacing (ATP) to terminate rapid
      ventricular tachycardias (VTs) (cycle length 240-320 ms) is predicated on the
      ability of implantable cardioverter defibrillators (ICDs) to distinguish rapid VT
      from ventricular fibrillation (VF). We set out to compare the time to device
      charging following the induction of VF of various ICD multizone detection
      algorithms for rapid VT/VF discrimination. METHODS AND RESULTS: Data on the time
      to device charging following the induction of VF at the time to device
      implantation were collected on 62 consecutive patients in a nonrandomized
      prospective cohort fashion. Multizone programming for the Boston Scientific,
      Medtronic, and St. Jude Medical devices was based on prior clinically validated
      data. Sixty-two subjects were studied (Boston Scientific = 16, Medtronic = 27,
      St. Jude Medical = 19) and 124 tests for VF detection were performed (Boston
      Scientific = 32, Medtronic = 54, St. Jude Medical = 38). Mean time to charging
      was significantly prolonged in the Boston Scientific group as was the percentage
      of tests where charge initiation occurred >5 seconds from VF-induction: 4.24,
      3.99, and 3.00 seconds and 19%, 4%, and 0% for the Boston Scientific, Medtronic,
      and St. Jude Medical groups, respectively, P < 0.05. ATP was the first therapy
      administered in 9.4% of tests in the Boston Scientific group. CONCLUSION: The
      Boston Scientific multizone VT/VF discrimination algorithm results in a prolonged
      time to VF detection, and consequently, prolonged time to appropriate initiation
      of device charging. Further studies are needed to determine whether prolonged
      detection times lead to clinically significant events.

PMID- 22385020
TI  - Post-natal growth in the rat pineal gland: a stereological study.
AB  - The purpose was to observe the changes in a rat pineal gland using stereological
      techniques during lactation and post-weaning periods. Thirty Wistar albino rats
      were studied during different post-natal periods using light microscopy. Pineal
      gland volume was estimated using the Cavalieri Method. Additionally, the total
      number of pinealocytes was estimated using the optical fractionator technique.
      Pineal gland volume displayed statistically significant changes between lactation
      and after weaning periods. A significant increase in pineal gland volume was
      observed from post-natal day 10 to post-natal day 90. The numerical density of
      pinealocytes became stabilized during lactation and decreased rapidly after
      weaning. However, the total number of pinealocytes continuously increased during
      post-natal life of all rats in the study. However, this increment was not
      statistically significant when comparing the lactation and after weaning periods.
      The increase in post-natal pineal gland volume may depend on increment of
      immunoreactive fibres, capsule thickness or new synaptic bodies.

PMID- 22385021
TI  - Maternal mood and neuroendocrine programming: effects of time of exposure and
      sex.
AB  - Adverse exposures that influence growth in prenatal and early postnatal periods
      are considered to influence vulnerability to chronic diseases via their effects
      on the neuroendocrine system. In humans, the assessment of the underlying
      mechanisms has been restricted. The present study aimed to investigate the
      effects of adverse early-life exposures, specifically maternal mood, on
      hypothlamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS) and
      parasympathetic nervous system (PNS) responses to an acute physiological
      stressor. In addition, we conducted a preliminary examination into whether these
      effects varied by time of exposure and sex. One hundred and thity-nine
      individuals (mean age 15.12 years) were recruited from the ALSPAC (Avon
      Longitudinal Study of Parents and Children) birth cohort. Participants underwent
      the CO(2) stress test and indices of the PNS, SNS and HPA axis were measured. Pre
      existing data on demographic and psychosocial factors of the mothers during
      pregnancy (18 and 32 weeks) and postnatally (8 weeks and 8 months) were
      extracted, as were participants' clinical and demographic data at birth.
      Increases in both pre- and postnatal anxiety and depression were associated with
      greater SNS reactivity to the stressor and slower recovery, as well as blunted
      HPA axis responses. Programming effects on the SNS appeared to be restricted to
      male offspring only. No consistent relationships were evident for any of the
      measures of pre-stress function. We have found preliminary evidence that both pre
      and postnatal maternal anxiety and depression have sustained programming effects
      on the SNS and HPA axis. Effects on the SNS were restricted to male offspring.

PMID- 22385022
TI  - The patient's view of quality in psychiatric outpatient care.
AB  - The influence of demographic characteristics on patients' ratings of the quality
      of psychiatric outpatient care has been given little attention in research. The
      aim of the present study is to elucidate the quality of psychiatric care among
      outpatients and investigate demographic and clinical factors associated with the
      way in which this quality is perceived. A sample of 1340 outpatients from 15
      general adult psychiatric clinics in Sweden completed the quality in psychiatric
      care-out-patient (QPC-OP), with a response rate of 71%. The patients' highest
      ratings were for Encounter; the lowest were for discharge. Most notably, quality
      of care was rated higher by women, older people, those with a partner, those with
      a lower educational level and those who were gainfully employed. In regard to
      visits to the clinic, higher quality of care was associated with shorter waiting
      time, better information and fewer professions encounters. Older people and those
      gainfully employed reported better mental health. Thus the QPC-OP was associated
      with both demographic and clinical factors. In particular, 'wanting to come back
      to the clinic' was the single strongest predictor of quality.

PMID- 22385023
TI  - Is the diurnal profile of salivary cortisol concentration a useful marker for
      measuring reported stress in acupuncture research? A randomized controlled pilot
      study.
AB  - OBJECTIVES: This pilot study on the use of traditional Chinese acupuncture (TCA)
      to treat chronic stress explored the use of the diurnal salivary cortisol profile
      as a potential outcome measure. DESIGN AND METHODS: Adult volunteers (n=18) with
      high self-reported stress levels, ascertained by screening with the Perceived
      Stress Scale 14, were randomized into three groups. Group 1 received weekly
      sessions of TCA for 5 weeks; Group 2 received attention only weekly (practitioner
      present and subject supine) for 5 weeks, and group 3 acted as a waiting-list
      control. A diurnal cortisol profile was constructed for each individual at nine
      data points: two at baseline, five during the intervention, and two
      postintervention. A salivary cortisol sample was taken at four time points (on
      waking, 30 minutes, 3 hours, and 12 hours after waking). OUTCOME MEASURES:
      Salivary cortisol concentrations were measured using a high-sensitivity salivary
      cortisol enzyme immunoassay. RESULTS: The cortisol awakening response showed an
      average increase during the intervention for both TCA and attention groups,
      indicating that for these two groups the cortisol response had normalized and
      they were in a lower state of stress. These trends did not reach statistical
      significance due to individual variation and the small number of study
      participants. The control group showed an overall decrease in the average morning
      increase over the same period. No significant difference in the day decline in
      cortisol was found between groups at any point in the study. CONCLUSIONS: This
      pilot study suggests that TCA could reduce stress and increase the morning rise
      of the cortisol profile; however, this was not distinguishable from the effect of
      attention only. Further work with a larger sample is necessary to provide a
      definitive answer regarding whether this could be sustained with more TCA
      treatments. The morning cortisol increase could be a useful outcome measure for
      monitoring the effects of treatment on perceived stress.

PMID- 22385024
TI  - Monotonic Bayesian semiparametric benchmark dose analysis.
AB  - Quantitative risk assessment proceeds by first estimating a dose-response model
      and then inverting this model to estimate the dose that corresponds to some
      prespecified level of response. The parametric form of the dose-response model
      often plays a large role in determining this dose. Consequently, the choice of
      the proper model is a major source of uncertainty when estimating such endpoints.
      While methods exist that attempt to incorporate the uncertainty by forming an
      estimate based upon all models considered, such methods may fail when the true
      model is on the edge of the space of models considered and cannot be formed from
      a weighted sum of constituent models. We propose a semiparametric model for dose
      response data as well as deriving a dose estimate associated with a particular
      response. In this model formulation, the only restriction on the model form is
      that it is monotonic. We use this model to estimate the dose-response curve from
      a long-term cancer bioassay, as well as compare this to methods currently used to
      account for model uncertainty. A small simulation study is conducted showing that
      the method is superior to model averaging when estimating exposure that arises
      from a quantal-linear dose-response mechanism, and is similar to these methods
      when investigating nonlinear dose-response patterns.

PMID- 22385025
TI  - Dyspnea in palliative care: expanding the role of corticosteroids.
AB  - Dyspnea is one of the most common symptoms in advanced cancer patients at the end
      of their life. It is often multifactorial with diverse malignant, nonmalignant,
      and cancer treatment related etiologies. Oxygen, opiates, and anxiolytics are
      commonly administered. Here a complex case of progressive dyspnea and its
      treatments in a patient with advanced pancreatic cancer is described, and its
      multiple potential contributing causes are identified and clinical responses
      evaluated. Literature review is conducted on pulmonary drug toxicity and tumor
      lymphangitic spread, and the role of corticosteroids in relieving dyspnea in the
      palliative care setting.

PMID- 22385027
TI  - Man in the mirror: research considerations for the care and appearance of men's
      skin.

PMID- 22385026
TI  - Guidelines for the psychosocial and bereavement support of family caregivers of
      palliative care patients.
AB  - BACKGROUND: Support for family caregivers, including bereavement follow-up, is a
      core function of palliative care. Many caregivers acknowledge positive aspects
      associated with the role; however a considerable proportion will experience poor
      psychological, social, financial, spiritual, and physical well-being and some
      will suffer from complicated grief. Many family caregivers have unmet needs and
      would like more information, preparation, and support to assist them in the
      caregiving role. There is a shortage of evidence-based strategies to guide health
      professionals in providing optimal support while the caregiver is providing care
      and after the patient's death. PURPOSE: To develop clinical practice guidelines
      for the psychosocial and bereavement support of family caregivers of palliative
      care patients. METHODS: (1) Literature review; (2) focus groups and structured
      interviews with key stakeholders within Australia; (3) national and international
      expert opinion to further develop and refine the guidelines using a modified
      Delphi process; and (4) endorsement of the guidelines from key palliative care,
      caregiver, and bereavement organizations (national and international). RESULTS:
      The guidelines were developed for multidisciplinary health care professionals and
      clinical services commonly involved in caring for adult patients receiving
      palliative care in a variety of care sites throughout Australia. These consensus
      based guidelines have been endorsed key Australian and international
      organizations. CONCLUSIONS: The guidelines may prove valuable for the
      international palliative care community and for generalist health care providers
      who occasionally care for palliative care patients. Research is recommended to
      explore the uptake, implementation, and effectiveness of the guidelines.

PMID- 22385028
TI  - Overview and trends in male grooming.
AB  - The use of cosmetics and medical cosmetic procedures by men has been widely
      ignored in dermatological research in the past, but it is finding increasing
      attention. As men are changing their habits and increasingly tend to use cosmetic
      products, the dermatologist will be asked for expert advice regarding efficacy
      and safety of cosmetics for male skin. For this service, dermatologists need to
      be aware of anatomical and physiological differences between male and female
      skin, about specific environmental stress factors affecting male skin, about
      cosmetic practices and product use especially regarding shaving, and about the
      counselling needs in men relating to protective cosmetic use.

PMID- 22385029
TI  - Insights into shaving and its impact on skin.
AB  - Male grooming has its roots in antiquity. Control and styling of facial hair has
      invariably required the development and use of metal instrumentation. Once crude
      and unreliable, it has latterly become sophisticated and subject to intense
      research and development at the highest scientific level. This paper describes
      how male grooming is being impacted by improvements in fundamental understanding
      of male skin. Skin issues associated with poor hair removal approaches are
      common, but are often overlooked or their aetiology misunderstood by patients and
      physicians. By incorporating advanced scientific measurement and imaging
      technology into clinical testing, insights are being gained into both the common
      concerns which men express and optimal solutions for these concerns. Specific
      aspects such as the study of nicks and cuts and the identification and release of
      trapped hairs are discussed. Finally, details are presented on how the individual
      elements of technologically advanced razors play a role in managing the skin and
      hair, highlighting further the complexity of the shaving process.

PMID- 22385030
TI  - Male skin and ingredients relevant to male skin care.
AB  - Male skin care needs are heavily influenced by the need to remove facial hair on
      a regular basis. Facial skin issues associated with poor hair removal approaches
      are common and include razor burn and irritation. This paper evaluates current
      research on shaving technology and how careful ingredient selection can
      contribute to male skin health. The importance of maintaining hair softness
      during the shave and restoring facial hydration post-shave is discussed. Data are
      presented on how post-shave moisturizers containing glycerine and emollients can
      create an environment for improved barrier function which can be further improved
      by incorporating specific ingredients such as niacinamide.

PMID- 22385031
TI  - Skin characteristics of Chinese men and their beard removal habits.
AB  - BACKGROUND: Grooming habits of men in China have some marked differences from
      those in other areas in the world, with a high percentage of men resorting to
      shaving with an electric razor. This is influenced by multiple factors, such as a
      lower facial hair growth density concentrated in a small area around the mouth.
      Further, there is limited knowledge and misconceptions around the alleged
      negative skin effects of blade shaving. OBJECTIVES: To compare skin in the shaved
      area with that of the rest of the face, and to compare the impact of shaving with
      a modern three-blade razor vs. electric shaving. METHODS: Pilot clinical studies
      including 50 and 40 healthy Chinese men, respectively. RESULTS: Skin in the
      shaved area is different from the rest of the face, with a higher temperature,
      lower hydration and diminished skin barrier function. Regular shaving with a
      modern multiblade razor was not statistically different from dry shaving in terms
      of impact on barrier function. CONCLUSIONS: Shaving with a modern multiblade
      razor could even deliver certain skin benefits in the area of facial oil control
      and reducing skin flakes.

PMID- 22385032
TI  - Clinical studies of sweat rate reduction by an over-the-counter soft-solid
      antiperspirant and comparison with a prescription antiperspirant product in male
      panelists.
AB  - BACKGROUND: Individuals with axillary hyperhidrosis have much higher than average
      sweat rates and are often prescribed anhydrous aluminum chloride (AlCl(3))
      solutions. Topical application of these solutions can be irritating to the skin,
      resulting in poor compliance and lower than desired efficacy. OBJECTIVE:
      Demonstrate the efficacy of an over the counter "clinical strength" soft-solid
      antiperspirant using a night time application regimen and compare to a
      prescription aluminum chloride (6.5%) antiperspirant using male panelists.
      METHODS: Gravimetric hot room efficacy testing (100 F and 35% Humidity) was
      performed comparing an over the counter soft-solid antiperspirant to placebo in a
      single test. Two separate gravimetric tests were placed comparing a prescription
      aluminum chloride (6.5%) antiperspirant to the same soft solid product using an
      intent to treat model. Skin irritation was assessed daily by a trained grader.
      RESULTS: Placebo testing resulted in 85% of panelists having a reduction in
      sweating rate greater than 50%. Comparison testing showed the over the counter
      soft solid reduced sweat rate by an average of 34% better than the prescription
      product while resulting significantly less skin irritation. CONCLUSIONS: Over the
      counter "clinical strength" soft-solid antiperspirants can be considered as an
      alternative treatment to aluminum chloride antiperspirants for the treatment of
      heavy sweating.

PMID- 22385034
TI  - Fifteen-Year Follow-Up Results of Presurgical Orthopedics Followed by Primary
      Correction for Unilateral Cleft Lip Nose in Program SEHATI in Indonesia.
AB  - Objective : To assess long-term effects of nasal correction in infancy on nasal
      form and growth in patients with unilateral cleft lip, alveolus, and palate
      (UCLP). Design : Retrospective longitudinal study. Patients : Seventeen patients
      with complete UCLP treated in Program SEHATI in Harapan Kita Children and
      Maternity Hospital, Indonesia, and followed for approximately 15 years were
      enrolled. Interventions : Subjects received presurgical orthopedics using a
      Hotz's plate and simultaneous primary lip and nose repair in which the lower
      lateral cartilage was repositioned through a reverse-U incision. Main Outcome
      Measures : Preoperative and postoperative nasal forms, including the nostril
      height and width ratio, the ratio of the height of the top of the alar groove,
      and the ratio of nostril surface areas were analyzed using color photos taken
      serially. One-way analysis of variance was used for statistical analyses. Results
      : The nostril height and width ratio and the height of the alar groove were
      significantly improved postoperatively and maintained for 15 years. The mean
      ratio of nostril surface areas was 1.01 +/- 0.12 fifteen years postoperatively,
      and there was no significant difference from the ratio 1 year postoperatively.
      The major persistent deformities were septal deviation and a small skin web on
      the nostril rim. Conclusions : Our primary cleft lip nose correction has provided
      an acceptable nose form and absence of disturbance of the nasal growth in
      patients with UCLP. However, the repositioning of the nasal cartilage at infancy
      might not eliminate the need for secondary correction after puberty.

PMID- 22385033
TI  - Quantitative Epstein-Barr virus shedding and its correlation with the risk of
      post-transplant lymphoproliferative disorder.
AB  - We postulated that quantitative monitoring of Epstein-Barr virus (EBV) shedding
      after transplantation could distinguish EBV-associated illnesses and predict
      clinical outcome. EBV DNA was measured in solid organ (SOT) and hematopoietic
      cell transplants (HCT) using our own real-time TaqMan EBV PCR. The proportion of
      patients who had EBV DNAemia post-transplant was significantly lower in HCT vs.
      SOT (p < 0.001). Over a 7.5-yr period, post-transplant lymphoproliferative
      disorder (PTLD) occurred in 66 (5.8%) of 1131 patients who met adequate
      monitoring criteria. SOT recipients developed PTLD significantly later than HCT
      recipients (median, 2.8 yr vs. 121 d; p < 0.001). PTLD was documented in 53 (14%)
      of 376 patients who had EBV in >=1 whole blood sample vs. 13 (2%) of 755 patients
      who had at least three EBV-negative blood samples and were never positive. PTLD
      risk in viremic patients increased with the peak quantity of EBV DNAemia (p <
      0.001). PTLD occurred in 37/333 (11%) of patients with peak blood levels 10(3) 
      10(5) copies/mL vs. 16/43 (37%) of patients with levels >10(5) (p < 0.001). EBV
      PCR was predictive in 29 (78%) of 37 patients tested within three wk prior to
      tissue diagnosis of PTLD, and thus, we conclude that EBV PCR with careful
      attention paid to changes in EBV DNAemia could lead to earlier diagnosis and
      treatment of PTLD.

PMID- 22385037
TI  - Forced convection during feedback approach curve measurements in scanning
      electrochemical microscopy: maximal displacement velocity with a microdisk.
AB  - In scanning electrochemical microscopy (SECM), an approach curve performed in
      feedback mode involves the downward displacement of a microelectrode toward a
      substrate while applying a bias to detect dissolved electroactive species at a
      diffusion-limited rate. The resulting measured current is said to be at steady
      state. In order to reduce the required measurement time, the approach velocity
      can be increased. In this paper, we investigate experimentally and theoretically
      the combination of diffusion and convection processes related to a moving
      microdisk electrode during feedback approaches. Transient modeling and numerical
      simulations with moving boundaries are performed, and the results are compared to
      the experimental approach curves obtained in aqueous solution. The geometry and
      misalignment of the microelectrode influence the experimental approach curves
      recorded at high approach velocities. The effects are discussed through the
      decomposition of the current into transient diffusional, radial convectional, and
      axial convectional contributions. Finally a ready-to-use expression is provided
      to rapidly evaluate the maximal approach velocity for steady state measurements
      as a function of the microelectrode geometry and the physical properties of the
      media. This expression holds for the more restrictive case of negative feedback
      as well as other modes, such as SECM approach curves performed at substrates
      displaying first order kinetics.

PMID- 22385035
TI  - Genetic influences on developmental smoking trajectories.
AB  - AIMS: To investigate the relative contribution of genetic and environmental
      factors on smoking trajectory membership and to test whether individual smoking
      trajectories represent phenotypical thresholds of increasing genetic risk along a
      common genetic liability dimension. DESIGN: Prospective study of a birth cohort
      of female like-sex twin pairs. SETTING: Participants completed diagnostic
      interview surveys four times from adolescence (average age 16) to young adulthood
      (average age 25). PARTICIPANTS: Female twins who had smoked >=100 cigarettes life
      time (n = 1466 regular smokers). MEASUREMENTS: Number of cigarettes smoked per
      day during the heaviest period of smoking (two waves) or during the past 12
      months (two waves). FINDINGS: A four-trajectory class solution provided the best
      fit to cigarette consumption data and was characterized by low (n = 564, 38.47%),
      moderate (n = 366, 24.97%) and high-level smokers (n = 197, 13.44%), and smokers
      who increased their smoking from adolescence to young adulthood (n =339, 23.12%).
      The best genetic model fit was a three-category model that comprised the low, a
      combined increasing + moderate and high trajectories. This trajectory
      categorization was heritable (72.7%), with no evidence for significant
      contribution from shared environmental factors. CONCLUSIONS: The way in which
      smoking patterns develop in adolescence has a high level of heritability.

PMID- 22385038
TI  - Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds:
      results of a randomized controlled trial.
AB  - BACKGROUND: The development of antibiotic resistance by microorganisms is an
      increasing problem in medicine. In chronic wounds, bacterial colonization is
      associated with impaired healing. Cold atmospheric plasma is an innovative
      promising tool to deal with these problems. OBJECTIVES: The 5-min argon plasma
      treatment has already demonstrated efficacy in reducing bacterial numbers in
      chronic infected wounds in vivo. In this study we investigated a 2-min plasma
      treatment with the same device and the next-generation device, to assess safety
      and reduction in bacterial load, regardless of the kind of bacteria and their
      resistance level in chronic wounds. METHODS: Twenty-four patients with chronic
      infected wounds were treated in a prospective randomized controlled phase II
      study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter
      alpha device, 10 with MicroPlaSter beta device (next-generation device) in
      addition to standard wound care. The patient acted as his/her own control.
      Bacterial species were detected by standard bacterial swabs and bacterial load by
      semiquantitative count on nitrocellulose filters. The plasma settings were the
      same as in the previous phase II study in which wounds were exposed for 5 min to
      argon plasma. RESULTS: Analysis of 70 treatments in 14 patients with the
      MicroPlaSter alpha device revealed a significant (40%, P<0.016) reduction in
      bacterial load in plasma-treated wounds, regardless of the species of bacteria.
      Analysis of 137 treatments in 10 patients with the MicroPlaSter beta device
      showed a highly significant reduction (23.5%, P<0.008) in bacterial load. No side
      effects occurred and the treatment was well tolerated. CONCLUSIONS: A 2-min
      treatment with either of two cold atmospheric argon plasma devices is a safe,
      painless and effective technique to decrease the bacterial load in chronic
      wounds.

PMID- 22385039
TI  - Specific profiles of neurocognitive and reading functions in a sample of 42
      Italian boys with Duchenne Muscular Dystrophy.
AB  - A group of 42 Italian boys with Duchenne Muscular Dystrophy was compared with a
      control group of 10 boys with Spinal Muscular Atrophy and Osteogenesis Imperfecta
      on tests assessing general intellectual ability, language, neuropsychological
      functions, and reading skills with the aim of describing a comprehensive profile
      of the various functions and investigating their interrelationships. The
      influence of general intellectual level on performance was analyzed. Further,
      correlations between various neuropsychological measures and language
      performances were computed for the group with Duchenne Muscular Dystrophy, as
      well as the correlations between reading scores and other cognitive and
      linguistic measures. A general lowering in VIQ, PIQ, and FSIQ scores was found to
      characterize the group with Duchenne Muscular Dystrophy. Expressive language
      skills were within the normal range, while syntactic and grammatical
      comprehension were significantly impaired. The presence of below-average reading
      performances was further confirmed. However, unlike previous studies on irregular
      orthographies, the present results show that (a) the mild reading difficulties
      found in the sample essentially concern speed rather than accuracy; (b) they
      concern word rather than nonword reading; (c) lower reading performances are
      related to lower scores in general IQ; (d) no correlations emerge with
      phonological abilities, verbal short-term memory, or working memory, but rather
      with long-term memory and lexical skills. This may suggest that language-specific
      effects modulate the cognitive expressions of Duchenne Muscular Dystrophy and
      raises the possibility that the dysfunctions underlying the reading difficulties
      observed in affected readers of regular orthographies involve different
      neurocognitive systems than the cortico-cerebellar circuits usually invoked.

PMID- 22385040
TI  - Dermatogeriatrics: a case for developing a new dermatology subspecialty.

PMID- 22385041
TI  - Blocking the pulmonary vein to left atrium conduction in addition to the entrance
      block enhances clinical efficacy in atrial fibrillation ablation.
AB  - BACKGROUND: The unidirectional pulmonary vein (PV) to left atrium (LA) conduction
      after achieving PV entrance block has not been evaluated. METHODS:
      Circumferential PV isolation was performed in 573 consecutive patients with
      atrial fibrillation (AF). The unidirectional PV to LA conduction and its
      influence on clinical outcomes were evaluated. RESULTS: A total of 341
      ipsilateral PVs (29.7%) with spontaneous activities (SAs) were documented in 231
      patients (40.3%). The unidirectional PV to LA conduction was confirmed in 11
      ipsilateral PVs (3.2%) of 11 patients (4.8%). Patients were classified to three
      groups: Group A (had unidirectional PV to LA conduction during SAs), Group B
      (with SAs but without PV to LA conduction), and Group C (without SAs). During a
      30-minute observation, the reconnection incidence was higher in Group A (45.4%)
      than in Group B (13.9%, P = 0.042) and Group C (11.5%, P = 0.018). The
      reconnection time was shorter in Group A (10.8 +/- 9.8 minutes) than that in
      Group B (20.7 +/- 8.0 minutes, P = 0.037) and Group C (21.2 +/- 8.2 minutes, P =
      0.022). All 11 PVs were successfully isolated and bidirectional block was
      achieved. CONCLUSION: Unidirectional entrance block with SAs in PVs may not be a
      good indication of complete PV isolation. Bidirectional block of the PV-LA
      junction can reduce the acute PV reconnection and may reduce the chronic AF
      recurrence in patients undergoing circumferential PV isolation.

PMID- 22385042
TI  - Histamine H4 receptor ligands and their potential therapeutic applications: an
      update.
AB  - INTRODUCTION: Several studies underlined the critical role of histamine H4
      receptor (H4R) in inflammation, thus H4 modulators have been suggested as
      promising drug candidates in inflammatory diseases. First H4 ligands typically
      have indole or amino-pyrimidine scaffolds. During the last few years, however,
      serious efforts have been made to identify novel H4 chemotypes with improved
      pharmacodynamic and pharmacokinetic properties. AREAS COVERED: Areas covered in
      this review include an overview on H4 ligands published in scientific papers, as
      well as in patent applications between 2009 and 2011. Recently discovered
      scaffolds possessing significant H4 activity were analyzed and their therapeutic
      potential was reviewed. EXPERT OPINION: Recent results from the scientific
      literature and novel patent applications reinforce the major role of H4R in
      inflammatory diseases such as pruritus, asthma, inflammatory pain and allergic
      rhinitis. Novel studies suggest further indications of H4 modulators in cancer,
      neuropathic pain, vestibular disorders and type 2 diabetes. The number of active
      H4 chemotypes was increased significantly. The first H4 antagonist entered to
      clinics and the results from a proof-of-concept Phase II clinical study is
      expected to be disclosed soon.

PMID- 22385043
TI  - RANTES-mediated control of excitatory amino acid release in mouse spinal cord.
AB  - The impact of Regulated upon Activation Normal T cells Expressed and Secreted
      (RANTES) on the release of pre-loaded [3H]D-aspartate ([3H]D-ASP) from mouse
      spinal cord synaptosomes was investigated. RANTES (0.01-1 nM) failed to affect
      the spontaneous release, but facilitated the 15 mM K+-evoked overflow of [3H]D
      ASP. Incubation of synaptosomes with antibodies raised against the chemokine
      receptor (CCR)1 and CCR5 proteins prevented RANTES-induced facilitation of
      glutamate exocytosis, whereas anti-CCR3 antibody was inefficacious. Accordingly,
      BX513 and D-Ala-peptide T-amide (DAPTA) CCR1 and CCR5 antagonists, respectively,
      prevented RANTES-induced effect, whereas the CCR3 antagonist SB 328437 was
      inactive. To compare these findings to previous results, we quantified the
      effects of CCR antagonists on the RANTES-induced modifications of the spontaneous
      and the K+-evoked [3H]D-ASP release in the mouse cortex. Here, CCR1 and CCR5, but
      not CCR3, antagonists prevented the RANTES-mediated [3H]D-ASP release, whereas
      RANTES-induced inhibition of the 12 mM K+-evoked [3H]D-ASP exocytosis was also
      antagonized by SB 328437. Facilitation of glutamate exocytosis in spinal cord
      relied on PLC-dependent mobilization of Ca2+ from IP3-sensitive stores; adenylyl
      cyclase was not involved. CCR1, CCR3 and CCR5 receptor proteins were present in
      spinal cord synaptosomal and gliosomal lysates, although RANTES-induced changes
      to glutamate release could not be observed in gliosomes. Our results confirm the
      role of RANTES as modulator of glutamate transmission.

PMID- 22385044
TI  - Ayurvedic gender differences revisited.

PMID- 22385045
TI  - Effect of a Japanese energy healing method known as Johrei on viability and
      proliferation of cultured cancer cells in vitro.
AB  - OBJECTIVES: The objective was to explore the effect of a Japanese energy healing
      method known as Johrei on the viability and proliferation of cultured human
      cancer cells in vitro. DESIGN: A randomly selected 96-well plate or a culture
      dish of various types of human cancer cell lines in culture were exposed to
      Johrei treatment. For comparison purpose, an equal number of untreated or
      volunteer-treated cultures were chosen as the control group. Johrei treatment was
      repeatedly performed at appropriate time intervals over the course of the
      experiments. Cell viability was examined by a colorimetric assay with a Cell
      Counting kit. Morphological changes were analyzed by phase-contrast and time
      lapse microscopy. Cell proliferation and early and late stages of cell death were
      also determined with the use of a bromodeoxyuridine (BrdU) cell proliferation
      assay kit and an Annexin V-FLUOS Staining kit, respectively. OUTCOME MEASURES:
      Quantitative data were presented as means+/-standard deviation. The outcome
      measures were the differences in viable cell numbers that remained under healing
      practice versus control conditions, and the statistical significance of
      differences in their mean values was assessed. RESULTS: The viability loss of
      cultured human cancer cells in the Johrei group was significantly higher than
      that of either of the control groups, despite the fact that the responsiveness to
      Johrei varied with different cancer cell types. The proliferation rate of gastric
      cancer cells exposed to Johrei treatments for 72 hours was more significantly
      decreased compared with that of the untreated cells, whereas the extent of dying
      and/or dead cells in the Johrei group was more profound than that of the
      untreated cells. CONCLUSIONS: These results provide evidence that Johrei
      treatment induces the viability loss of various cancer cells in vitro, mainly due
      to the increased cell death and the decreased proliferation.

PMID- 22385046
TI  - Some implications of the reported effects of Johrei on the viability and
      proliferation of cultured cancer cells in vitro.

PMID- 22385047
TI  - Preliminary evidence hints at a protective role for boron in urolithiasis.

PMID- 22385048
TI  - Turmeric (Curcuma longa L.) volatile oil inhibits key enzymes linked to type 2
      diabetes.
AB  - Anti-diabetic capacity of Curcuma longa volatile oil in terms of its ability to
      inhibit glucosidase activities was evaluated. Turmeric volatile oils inhibited
      glucosidase enzymes more effectively than the reference standard drug acarbose.
      Drying of rhizomes was found to enhance alpha-glucosidase (IC50 = 1.32-0.38
      MUg/ml) and alpha-amylase (IC50 = 64.7-34.3 MUg/ml) inhibitory capacities of
      volatile oils. Ar-Turmerone, the major volatile component in the rhizome also
      showed potent alpha-glucosidase (IC50 = 0.28 MUg) and alpha-amylase (IC50 = 24.5
      MUg) inhibition.

PMID- 22385049
TI  - Comparable outcomes between unrelated and related donors after reduced-intensity
      conditioning allogeneic hematopoietic stem cell transplantation in patients with
      high-risk multiple myeloma.
AB  - The purpose of this study was to assess the results of allogeneic stem cell
      transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from
      matched related donors (MRD) and unrelated donors (URD) in 40 patients with high
      risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23
      patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients
      (98%) received one or more autologous transplantation. The median follow-up was
      22 months (1-49). None of our patient experienced a graft rejection. The
      cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs.
      (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no
      different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM
      probabilities were lower in the unrelated group 12% vs. 22% in the related group
      (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation
      overall and progression-free survivals, 59% and 42%, respectively compared to
      patients with related donor transplantation, 66% and 44% (P = 0.241). In
      conclusion, these results suggest that URD in MM is feasible. The small number of
      patients with URD emphasizes the need to delineate indications and perform
      prospective protocols.

PMID- 22385050
TI  - The relationship between compulsive exercise and emotion regulation in
      adolescents.
AB  - OBJECTIVE: Compulsive exercise is suggested to be a strategy to regulate
      emotions. This suggestion has never been studied in adolescents. Therefore, this
      study examined the cross-sectional association between emotion regulation and
      compulsive exercise attitudes in adolescents. DESIGN: A cross-sectional design
      was employed for this study. METHOD: A sample of 1,630 adolescent boys and girls
      completed self-report measures of compulsive exercise, emotion regulation, and
      disordered eating attitudes, as part of ongoing research into exercise and eating
      attitudes in adolescents. RESULTS: Compulsive exercise was significantly
      associated with emotion regulation, after controlling for disordered eating
      attitudes. Among boys, compulsive exercise was associated with internal
      functional, internal dysfunctional, and external functional emotion regulation
      strategies. In girls, internal functional and internal dysfunctional emotion
      regulation strategies predicted compulsive exercise. CONCLUSIONS: Adolescents'
      compulsivity towards exercise is positively associated with different emotion
      regulation strategies. More work is needed to identify whether emotion regulation
      strategies longitudinally predict compulsive exercise.

PMID- 22385051
TI  - On "black swans" and "perfect storms": risk analysis and management when
      statistics are not enough.
AB  - Two images, "black swans" and "perfect storms," have struck the public's
      imagination and are used--at times indiscriminately--to describe the unthinkable
      or the extremely unlikely. These metaphors have been used as excuses to wait for
      an accident to happen before taking risk management measures, both in industry
      and government. These two images represent two distinct types of uncertainties
      (epistemic and aleatory). Existing statistics are often insufficient to support
      risk management because the sample may be too small and the system may have
      changed. Rationality as defined by the von Neumann axioms leads to a combination
      of both types of uncertainties into a single probability measure--Bayesian
      probability--and accounts only for risk aversion. Yet, the decisionmaker may also
      want to be ambiguity averse. This article presents an engineering risk analysis
      perspective on the problem, using all available information in support of
      proactive risk management decisions and considering both types of uncertainty.
      These measures involve monitoring of signals, precursors, and near-misses, as
      well as reinforcement of the system and a thoughtful response strategy. It also
      involves careful examination of organizational factors such as the incentive
      system, which shape human performance and affect the risk of errors. In all
      cases, including rare events, risk quantification does not allow "prediction" of
      accidents and catastrophes. Instead, it is meant to support effective risk
      management rather than simply reacting to the latest events and headlines.

PMID- 22385052
TI  - Moderate Red Wine Drinking Does Not Help Cut Women's Breast Cancer Risk.

PMID- 22385055
TI  - New Pharmacological Approaches in Infants with Hypoxic-Ischemic Encephalopathy.
AB  - New knowledge of the pathophysiology and evolution of hypoxic-ischemic brain
      injuries has made feasible interventions to improve clinical outcomes for
      newborns surviving birth asphyxia. Brain injury following hypoxic-ischemic insult
      is a complex process evolving over hours to days, which provides a unique window
      of opportunity for neuroprotective treatment interventions. The specific
      pathologic processes preceding the onset of irreversible cerebral injury appear
      to be a combination of several mechanisms that are variable according to the
      severity and duration of the insult and to biochemical modifications in the
      brain. Advances in neuroimaging, brain monitoring techniques, and tissue
      biomarkers have improved the ability to diagnose, monitor, and care for newborn
      infants with neonatal encephalopathy, as well as to predict their outcome. The
      role of oxidative stress in newborn morbidity with respect to the higher risk of
      free radical damage in these babies is growing. However, challenges remain in
      early identification of infants at risk for neonatal encephalopathy,
      determination of timing and extent of hypoxic-ischemic brain injury, as well as
      optimal management and treatment duration. Potential neuroprotective strategies
      targeting different pathways leading to neuronal cell death in response to
      hypoxic-ischemic insult have been investigated: hypothermia, erythropoietin,
      iminobiotin, deferioxamine, magnesium, allopurinol, xenon, melatonin and statins.
      Hypothermia is currently the only recognized beneficial therapy. However, many
      infants still develop significant adverse outcomes. It is becoming evident that
      the association of moderate hypothermia with neuroprotective drugs may enhance
      the outcome. By virtue of their pleiotropic effects without toxic effects,
      melatonin and statins may act at different levels of the multiple mechanisms
      responsible for the progression of the neurodegenerative process and represent
      promising neuroprotectants, alone or as additional adjunctive therapy, for
      reducing brain injury and its long-term sequelae in infants. More clinical
      studies are needed to clarify the role of these potential neuroprotective drugs.

PMID- 22385059
TI  - Pharmacokinetics of Aminoglycosides in the Newborn.
AB  - Aminoglycosides have played a major role in antimicrobial therapy since their
      discovery in the 1940s. Their bactericidal efficacy in gram-negative infections,
      synergism with beta-lactam antibiotics, limited bacterial resistance, and low
      cost have given these agents a firm place in antimicrobial treatment. After
      penicillins, aminoglycosides are the most commonly used drugs in the neonatal
      intensive care unit. While the pharmacodynamic action on the bacterial target is
      obviously the same in neonates as compared to children and adults, dramatic
      differences exist in terms of pharmacokinetics. Renal function is the most
      important determinant in respect to the elimination of aminoglycosides and,
      depending on the age and development of the newborn infant, dramatic changes in
      renal clearing capacity have been documented. The incorporation of this knowledge
      about the developing kidney has, very recently, resulted in a revised
      aminoglycoside dosing guideline for use in newborn infants. This article will
      therefore address the rationale behind this new dosing regimen and also explain
      why this has resulted in clinically important changes in how to perform
      therapeutic drug monitoring of aminoglycosides in neonates to ensure safe and
      effective use of these frequently used medicines in this vulnerable population.

PMID- 22385062
TI  - Vitamin A in Prevention of Bronchopulmonary Dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) remains one of the most serious challenges in
      the care of the very preterm infants, affecting approximately one-quarter of
      infants born <1500g birth weight and 30% <1000g. Oxygen toxicity may contribute
      to its pathogenesis. Vitamin A concentrations are lower in BPD infants which may
      result in a reduction of the antioxidant protection. It has been found to up
      regulate genes necessary for fetal lung growth and increase surfactant production
      in animal models and is also involved in the modulation of immunological and
      inflammatory responses by regulation of cytokine production. Retinoic acid plays
      a key role in lung development improving alveolar septation. Evidence exists that
      vitamin A supplementation for very low birth weight (VLBW) infants, beyond that
      routinely given in multivitamin preparations, is associated with a reduction in
      death or BPD. So, parenteral administration of vitamin A to the newborn is one of
      the current recommended preventive therapies for BPD (number needed to treat 12;
      95% CI:6-94; The information on long-term neurodevelopmental status suggests no
      evidence of either benefit or harm. Estimates for cerebral palsy range from a
      number needed to treat of 11 to a number needed to harm of 33. Nowadays, is seems
      that administration of antenatal vitamin A to the mother in late pregnancy
      associated with neonatal supplementation can better prevent the development of
      BPD in areas of endemic vitamin A deficiency. The benefits, in terms of vitamin A
      status, safety and acceptability of delivering vitamin A in an intravenous
      emulsion compared with repeat intramuscular injections, the association of
      vitamin A prenatal and postnatal, as well as the effectiveness and safety of
      administered high dose vitamin A in ELBW infants waits evaluation and should be
      assessed in further trials.

PMID- 22385063
TI  - Pharmacokinetics of Drugs in Neonates: Pattern Recognition Beyond Compound
      Specific Observations.
AB  - Although the principles of drug disposition also apply in neonates, their
      specific characteristics warrant focussed assessment. Children display maturation
      in drug disposition, but this is most prominent in the first year of life.
      Besides maturational aspects of drug absorption and distribution, maturation
      mainly relates to (renal) elimination and (hepatic) metabolic clearance. Renal
      elimination clearance in early life is low and almost completely depends on
      glomerular filtration. Despite the overall low clearance, interindividual
      variability is already extensive and can be predicted by covariates like
      postmenstrual age, postnatal age, co-administration of a non-selective cyclo
      oxygenase inhibitor, growth restriction or peripartal asphyxia. These findings
      are illustrated by observations on amikacin and vancomycin. Variation in
      phenotypic metabolic clearance is based on constitutional, environmental and
      genetic characteristics. In early life, it mainly reflects ontogeny, but other
      covariates may also become relevant. Almost all phase I and phase II metabolic
      processes display ontogeny in a iso-enzyme specific pattern. The impact of
      covariates like postmenstrual age, postnatal age, disease state characteristics
      and polymorphisms are illustrated based or 'probe' drugs (paracetamol, tramadol,
      propofol) administered as part of their medical treatment in critically ill
      neonates. The description of a compound specific pattern is beyond compound
      specific relevance. The maturational patterns described and the extent of the
      impact of covariates can subsequently be applied to predict in vivo time
      concentration profiles for compounds that undergo similar routes of elimination.
      Through improved predictability, such maturational models can serve to improve
      both the clinical care and feasibility and safety of clinical studies in
      neonates.

PMID- 22385064
TI  - Connecting breeding and wintering habitats of migratory piscivorous birds:
      implications for tracking contaminants (Hg) using multiple stable isotopes.
AB  - Contaminant concentrations in migratory species are complicated by differential
      accumulation and elimination among geographically separated biomes. Double
      crested cormorants ( Phalacrocorax auritus ) are used as monitors of Hg in North
      America; however, migration from northern breeding colonies to southern marine,
      freshwater, and aquaculture systems exposes individuals to spatiotemporal
      variations in contaminant uptake. We used stable isotopes (delta(34)S,
      delta(13)C, delta(15)N, delta(2)H) in primary feathers and a combined Bayesian
      assignment and isotopic threshold model to identify feather origins and the
      potential winter use of aquaculture (delta(34)S < 100/00, delta(13)C > -140/00),
      freshwater (delta(34)S < 100/00, delta(13)C < -200/00), and marine habitats
      (delta(34)S > 100/00). This approach allowed us to contrast body burden Hg
      derived from the breeding and wintering grounds, as well as from marine and
      freshwater habitats. We found feathers grown on Lake Winnipeg had greater Hg
      concentrations (mean = 4.26 +/- 1.47 MUg/g fresh weight; n = 20) than winter
      grown feathers (3.19 +/- 1.64 MUg/g; n = 19), but Hg in winter-grown feathers was
      not related to any specific habitat. Isotopic assays of tissues of migratory
      birds allowed the source and degree of contaminant exposure to be identified
      throughout the annual cycle.

PMID- 22385065
TI  - Frontalis-based island pedicle flaps for the single-stage repair of large defects
      of the forehead and frontal scalp.
AB  - BACKGROUND: Medium- to large-sized surgical defects of the forehead and frontal
      scalp provide a challenge for the reconstructive surgeon. OBJECTIVES: To
      highlight the utility of a frontalis-based island pedicle flap (FIPF) for the
      single-stage, aesthetic reconstruction of such defects. METHODS: The design and
      detailed surgical technique required for a FIPF are described. RESULTS: The long
      term results are illustrated. CONCLUSIONS: FIPFs, despite significant tissue
      dissection, are readily performed under local anaesthesia and are well tolerated
      by patients. The FIPF adds to the dermatological surgeon's armamentarium in the
      reconstruction of large defects of the central forehead and frontal scalp.

PMID- 22385066
TI  - Use of a 'microecological technique' to study crime incidents around methadone
      maintenance treatment centers.
AB  - AIMS: Concern about crime is a significant barrier to the establishment of
      methadone treatment centers (MTCs). Methadone maintenance reduces crime among
      those treated, but the relationship between MTCs and neighborhood crime is
      unknown. We evaluated crime around MTCs. SETTING: Baltimore City, MD, USA.
      PARTICIPANTS: We evaluated crime around 13 MTCs and three types of control
      locations: 13 convenience stores (stores), 13 residential points and 10 general
      medical hospitals. MEASURES: We collected reports of Part 1 crimes from 1 January
      1999 to 31 December 2001 from the Baltimore City Police Department. DESIGN:
      Crimes and residential point locations were mapped electronically by street
      address (geocoded), and MTCs, hospitals and stores were mapped by visiting the
      sites with a global positioning satellite (GPS) locator. Concentric circular
      'buffers' were drawn at 25-m intervals up to 300 m around each site. We used
      Poisson regression to assess the relationship between crime counts (incidents per
      unit area) and distance from the site. FINDINGS: There was no significant
      geographic relationship between crime counts and MTCs or hospitals. A significant
      negative relationship (parameter estimate -0.3127, P < 0.04) existed around
      stores in the daytime (7 am-7 pm), indicating higher crime counts closer to the
      stores. We found a significant positive relationship around residential points
      during daytime (0.5180, P < 0.0001) and at night (0.3303, P < 0.0001), indicating
      higher crime counts further away. CONCLUSIONS: Methadone treatment centers, in
      contrast to convenience stores, are not associated geographically with crime.

PMID- 22385067
TI  - Acute overdose of enteric-coated valproic acid and olanzapine: unusual
      presentation and delayed toxicity.

PMID- 22385068
TI  - Scalable imprinting of shape-specific polymeric nanocarriers using a release
      layer of switchable water solubility.
AB  - There is increasing interest in fabricating shape-specific polymeric nano- and
      microparticles for efficient delivery of drugs and imaging agents. The size and
      shape of these particles could significantly influence their transport properties
      and play an important role in in vivo biodistribution, targeting, and cellular
      uptake. Nanoimprint lithography methods, such as jet-and-flash imprint
      lithography (J-FIL), provide versatile top-down processes to fabricate shape
      specific, biocompatible nanoscale hydrogels that can deliver therapeutic and
      diagnostic molecules in response to disease-specific cues. However, the key
      challenges in top-down fabrication of such nanocarriers are scalable imprinting
      with biological and biocompatible materials, ease of particle-surface
      modification using both aqueous and organic chemistry as well as simple yet
      biocompatible harvesting. Here we report that a biopolymer-based sacrificial
      release layer in combination with improved nanocarrier-material formulation can
      address these challenges. The sacrificial layer improves scalability and ease of
      imprint-surface modification due to its switchable solubility through simple ion
      exchange between monovalent and divalent cations. This process enables large
      scale bionanoimprinting and efficient, one-step harvesting of hydrogel
      nanoparticles in both water- and organic-based imprint solutions.

PMID- 22385070
TI  - High-efficiency electrochemical hydrogen evolution based on surface autocatalytic
      effect of ultrathin 3C-SiC nanocrystals.
AB  - Good understanding of the reaction mechanism in the electrochemical reduction of
      water to hydrogen is crucial to renewable energy technologies. Although previous
      studies have revealed that the surface properties of materials affect the
      catalytic reactivity, the effects of a catalytic surface on the hydrogen
      evolution reaction (HER) on the molecular level are still not well understood.
      Contrary to general belief, water molecules do not adsorb onto the surfaces of 3C
      SiC nanocrystals (NCs), but rather spontaneously dissociate via a surface
      autocatalytic process forming a complex consisting of -H and -OH fragments. In
      this study, we show that ultrathin 3C-SiC NCs possess superior electrocatalytic
      activity in the HER. This arises from the large reduction in the activation
      barrier on the NC surface enabling efficient dissociation of H(2)O molecules.
      Furthermore, the ultrathin 3C-SiC NCs show enhanced HER activity in
      photoelectrochemical cells and are very promising to the water splitting based on
      the synergistic electrocatalytic and photoelectrochemical actions. This study
      provides a molecular-level understanding of the HER mechanism and reveals that
      NCs with surface autocatalytic effects can be used to split water with high
      efficiency thereby enabling renewable and economical production of hydrogen.

PMID- 22385071
TI  - The gap that makes us desperate: paths from language to mental health.
AB  - Although past research provided some clues about the relation of language use
      with mental health, the mediatory functions of personality variables in this
      relationship have been ignored. This research examined the mediatory role of self
      concept clarity in the relationship between language use perceived by individuals
      and mental health indicators including anxiety, depression, and alexithymia.
      Based on the theoretical framework suggested by Simsek (2010), two studies sought
      to test two alternative structural equation models in data from university
      students in the first study (n = 250) and data from other groups in the second
      study (n = 331). The first model assumed that the relationship of language use
      with anxiety, depression, and alexithymia was mediated by self-concept clarity.
      The second model tested the mediatory role of both anxiety and self-concept
      clarity in this relationship. The results of the first study showed that the
      second model fitted better to the data than the first. Consistent with the first
      study, the results of the second study confirmed that the second model produced
      better goodness of fit statistics than the first model.

PMID- 22385072
TI  - Alternating pacemaker AV delays: the long and short of it.

PMID- 22385073
TI  - Combination of fractional erbium-glass laser and topical therapy in melasma
      resistant to triple-combination cream.
AB  - BACKGROUND: Melasma is a common melanosis often difficult to treat. OBJECTIVE:
      The aim of this paper was to report on the safety and efficacy of non-ablative
      fractional photothermolysis combined with the use of triple-combination cream
      (TCC) on a large population with melasma resistant (i.e., with no complete/near
      complete clearing) to TCC alone. METHODS: Seventy-six patients with resistant
      melasma underwent a combined treatment protocol. The protocol consisted of a TCC
      (hydroquinone 4%, retinoic acid 0.03%, hydrocortisone butyrate 0.1%) applied
      daily for 10 days followed by four laser treatments performed in 3-week intervals
      with a fractional 1540-nm erbium-glass laser. During these intervals, and for 3
      months after the last laser session, TCC was also applied daily following a
      "pulse-therapy" scheme. Improvement was assessed by the melasma-area-and-severity
      index (MASI) score. RESULTS: At 1 month, marked (>75%) and moderate (51-75%)
      clearing of melasma were observed in 46 of 76 (67.1%) and 12 of 76 (21%) cases,
      respectively. At 6 months, we noticed a marked improvement in 16 of 76 (21.1%)
      and no improvement in 33 of 76 (43.4%) patients. CONCLUSION: Our study proposes
      the combination of NFP/TCC as a useful therapy for patients with melasma
      resistant to TCC alone, but it shows that its long-term efficacy is limited.

PMID- 22385074
TI  - Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal
      cell carcinoma in the face: a prospective randomized controlled study.
AB  - BACKGROUND: Imiquimod 5% cream can reduce or clear superficial and small nodular
      basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs
      micrographic surgery (MMS) to decrease defect size. OBJECTIVES: To study if a
      pretreatment with imiquimod 5% cream decreases defect size after MMS. In
      addition, to study the effect on the number of Mohs stages and reconstruction
      time. METHODS: Seventy patients aged >18 years with a primary nodular BCC in the
      face were included. The imiquimod group used imiquimod 5% cream for 4 weeks,
      before MMS. The control group was treated with MMS only. Tumour and defect sizes
      were measured. We noted the number of Mohs stages, reconstruction time and side
      effects. RESULTS: The median percentage increase in area from tumour size at
      baseline to the post-MMS defect for the imiquimod group was significantly less
      compared with the control group, 50% vs. 147% (P < 0.001). A tendency towards
      fewer Mohs stages in the imiquimod group was observed and the reconstruction time
      was significantly shorter in this group (P = 0.01). CONCLUSIONS: Imiquimod 5%
      cream as pretreatment of MMS significantly reduced the tumour size in primary
      nodular BCC and reduced the surgical defect size. Further research is necessary
      to investigate cost-effectiveness.

PMID- 22385075
TI  - Polymorphisms in genes involved in inflammatory pathways in patients with sudden
      sensorineural hearing loss.
AB  - Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL)
      remains unclear, the pathologically increased permeability of blood vessels,
      elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the
      involvement of inflammation. Because SSNHL is considered a multifactorial
      disease, possibly caused by interactions between genetic factors and
      environmental factors, the authors investigated the associations of polymorphisms
      of inflammatory mediator genes with susceptibility to SSNHL. The authors compared
      72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age
      59.2 years; range 40-79) who participated in the National Institute for Longevity
      Sciences Longitudinal Study of Aging. Multiple logistic regression was used to
      obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL
      6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFalpha C - 863A, TNFRSF1B G593A, VEGF
      C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and
      any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the
      risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence
      interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094)
      in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3
      (adjusted for age, gender, and a history of hypertension, diabetes, or
      dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI,
      1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035
      2.692) in model 3. The remaining seven polymorphisms failed to show any
      associations with the risk of SSNHL. These data need to be confirmed on larger
      series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated
      with a risk of SSNHL. Because permeability of blood vessels in the inner ear is
      frequently increased in patients with SSNHL, inflammation of the inner ear might
      be involved.

PMID- 22385076
TI  - Molecular photovoltaic system based on fullerenes and carotenoids co-assembled in
      lipid/alkanethiol hybrid bilayers.
AB  - A hybrid molecular photovoltaic system, based on fullerene C(60) and lutein (a
      natural photosynthetic carotenoid pigment) that are assembled in a
      phospholipid/alkanethiol bilayer matrix, is described here. The assembly and
      photoconversion behaviors of such a system were studied by UV-vis spectroscopy,
      cyclic voltammetry, impedance spectroscopy, photoelectrochemical action
      spectroscopy, and photocurrent generation. While lutein itself is inefficient in
      generating photocurrent, it can strongly modulate photocurrents produced by
      fullerenes when coassembled in the lipid bilayer matrix presumably via
      photoinduced electron transfer. Our results thus provide a successful example of
      combining both synthetic and natural photoactive components in building molecular
      photovoltaic systems.

PMID- 22385077
TI  - CD133 as a target for colon cancer.
AB  - INTRODUCTION: Recent evidence based on cancer stem cell (CSC) models, is boosting
      the progress of translational research and providing relevant clinical
      implications in many tumour types, including colorectal cancer. The current
      failure of standard therapies is attributed to a small fraction of the primary
      cell population with stem-like characteristics, such as self-renewal and
      differentiation. Identification of CSCs is based on two different criteria of
      selection: stemness-selective conditions and direct isolation based on putative
      stem cell markers expression. CD133, a transmembrane glycoprotein, was associated
      with tumor-initiating cells derived from several histological variants of tumors,
      including colon. AREAS COVERED: In this review the current understandings about
      CD133 as putative marker of tumour-initiating cells in colorectal cancer (CRC) is
      described. The focus of the discussion is on the need for additional markers to
      better identify the cell population able to recapitulate the parental tumor in
      immunocompromised mice. EXPERT OPINION: Identification and characterization of
      CSCs represents a relevant issue to define innovative therapeutic approaches,
      overcoming the emergence of cancer cell clones capable of evading standard
      therapy.

PMID- 22385078
TI  - Effects of traditional Japanese massage therapy on various symptoms in patients
      with Parkinson's disease: a case-series study.
AB  - OBJECTIVES: Massage therapy is one of the most commonly used complementary
      therapies for patients with Parkinson's disease (PD). The aim of this preliminary
      study was to evaluate the effects of traditional Japanese massage therapy on
      various symptoms of patients with PD. DESIGN: The study design was a case series
      study. SETTING: The study was conducted at the Center for Integrative Medicine,
      Tsukuba University of Technology, Japan. SUBJECTS: The subjects were 10 patients
      with idiopathic PD (mean age, 69.6+/-7.7 years; range, 55-85 years) who presented
      for consultation with a neurologist between February and April 2009 and who
      desired massage therapy in conjunction with standard pharmaceutical treatment.
      INTERVENTION: The intervention comprised a 30-minute session of traditional
      Japanese massage in conjunction with standard conventional medication. OUTCOME
      MEASURES: The outcome measures were as follows: Gait speed in the 20-m walk test
      (10-m walk and return) for gait disturbance, angular range of shoulder joint
      motion for frozen shoulder, and a visual analogue scale (VAS) for assessing the
      severity of each of various symptoms (hypophonia, shoulder stiffness, muscle
      pain, heaviness or lassitude of a body part, and fatigue), as determined before
      and after the massage session. RESULTS: (1) Patients with gait disturbance showed
      improved gait speed, (2) those with frozen shoulder showed improved range of
      motion of the shoulder joint, and (3) VAS scores for assessing the severity of
      other subjective symptoms were improved. CONCLUSIONS: These results suggest that
      traditional Japanese massage therapy used in combination with medication is
      effective for alleviating various symptoms in patients with PD and may contribute
      to enhancing their health-related quality of life. Larger studies with a control
      group are required to verify these findings.

PMID- 22385079
TI  - Experimental finding on the electromagnetic information transfer of specific
      molecular signals mediated through the aqueous system on two human cellular
      models.
AB  - BACKGROUND: Recently the authors reported the experimental evidence of the
      developing concept of Electro Magnetic Information Transfer (EMIT) of specific
      molecular signals directly and continuously on target cell picking up the
      molecular signals from the source chemical effector. This was in agreement with
      the pioneering work of Jaques Benveniste suggesting that the electronic
      transmission of the 4-phorbol-12-myristate-13-acetate (PMA) signals could be
      transferred to target neutrophils by an oscillator when coupled to two
      electromagnetic coils demonstrating the same biologic activity and so mimicking
      the biologic function of the original chemical active molecule. The present work
      is the further development of recent research designed to verify the hypotheses
      that water could record and replay the EMIT from biologic active chemical
      molecules. METHODS: Retinoic acid, a well-known chemical differentiating agent,
      was placed at room temperature in the input coil connected to an oscillator (VEGA
      select 719), while culture medium for human neuroblastoma cell (LAN-5) and NT2/D1
      stem teratocarcinoma human cells was placed into the output coil and exposed to
      signals for 1 hour. At the end the oscillator was switched off and LAN-5
      neuroblastoma and NT2/D1 stem teratocarcinoma cells were seeded, respectively,
      into the medium conditioned as reported into an incubator under controlled
      conditions. After 5 days of incubations, cells were examined by different
      strategies such as morphological and biochemical parameters. RESULTS: It was
      demonstrated that the electromagnetic signals coming from the retinoic acid
      molecule could be recorded and stored by the aqueous system of the cell culture
      medium. Cells seeded in the electronically conditioned medium received physical
      information generating a statistically significant decrease in metabolic activity
      and changes in phenotypical structure with protrusion typical of differentiated
      neuronal cells. CONCLUSIONS: These experimental results provide some evidence
      that water could be tuned in a resonant manner by the EMIT procedure
      appropriately carried through a carrier frequency provided by the oscillator in a
      manner that seems related to the chemical structure of the source molecule as, in
      this case, retinoic acid.

PMID- 22385080
TI  - Fabrication of glyconanoparticle microarrays.
AB  - We report a new type of microarray, based on glyconanoparticles (GNPs), to study
      glycan-lectin interactions. GNPs, synthesized by conjugating carbohydrate ligands
      on silica nanoparticles, were printed on a photoactive surface followed by
      covalent immobilization by light activation. The GNP microarrays could be probed
      by lectins labeled with fluorescein as well as fluorescein-doped silica
      nanoparticles (FSNPs). Results showed that FSNP as the label enhanced the signals
      for the higher affinity ligands than the lower ones.

PMID- 22385081
TI  - Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 (TIMPs -1
      and -2) in fibroblasts are early indicators of oral sub-mucous fibrosis and
      ageing.
AB  - Oral submucous fibrosis (OSMF) is associated with paan chewing, altered collagen
      metabolism, inflammation and the upregulation of numerous cytokines. OSMF
      fibroblasts accumulate senescent cells at an increased rate because of increased
      reactive oxygen species production and DNA double-strand breaks (DDBs), generated
      intrinsically by damaged mitochondria. This results in a reduced replicative
      lifespan. However, it is still unclear which other changes are intrinsic to the
      fibroblasts and associated with OSMF rather than the paan chewing habit or the
      OSMF environment. Both the oral epithelium and the mesenchyme have elevated
      levels of TGF-beta(1) in OSMF in vivo. However, in cultured fibroblasts, secreted
      levels of TGF-beta(1,) other cytokines and the matrix metalloproteinases 1 and 2
      showed no association with OSMF. In contrast, the tissue inhibitors of
      metalloproteinases, TIMP-1 and TIMP-2, were increased in 10/11 OSMF fibroblast
      cultures relative to normal and non-diseased paan user controls. OSMF fibroblast
      collagen levels were normal. TIMP levels correlated with replicative lifespan of
      the cultures but not with the presence of senescent cells, as senescent cell
      depletion in OSMF fibroblast cultures did not result in a reduction in either
      TIMP-1 or TIMP-2. However, the introduction of unrepairable DDBs into normal oral
      fibroblasts by ionizing radiation increased TIMP-1 and TIMP-2 secretion by two
      fold and seven-fold, respectively, within 5 days, replicating early senescence
      and the elevation seen in OSMF cultures. Therefore, increased fibroblast TIMP-1/2
      levels could be early disease-specific markers of OSMF onset, DDBs and ageing and
      may have clinical significance, as OSMF can be reversed in its early stages.

PMID- 22385082
TI  - Asymptomatic spinal dural arteriovenous fistulas: pathomechanical considerations.
AB  - OBJECT: Spinal dural arteriovenous fistulas (SDAVFs) consist of a shunt with
      converging feeding vessels arising from radiculomeningeal arteries and draining
      retrogradely via a radicular vein into the perimedullary veins, thereby causing
      progressive myelopathy due to venous hypertension in the spinal cord. The purpose
      of this study was to evaluate the hypothesis that the obstruction of radicular
      venous outlets could be an additional factor inducing symptomatic venous
      hypertension due to a decreased outflow in SDAVFs. METHODS: The authors compared
      the clinical and imaging findings in patients with asymptomatic SDAVFs identified
      incidentally at the upper thoracic region with the findings in symptomatic
      patients who harbored SDAVFs at the same level. RESULTS: All symptomatic patients
      presented with medullary dysfunction. The mean age of patients with asymptomatic
      SDAVF was 51.5 years, approximately 10 years younger than the patients with
      symptomatic SDAVF (64.1 years old). Despite the existence of dilated
      perimedullary vessels in the dorsal side of the spinal cord in all patients, the
      spinal cord edema seen in symptomatic patients was not detected on the MR images
      obtained in patients with asymptomatic SDAVF. The spinal angiograms of the
      asymptomatic patients distinctively demonstrated early radicular venous outflow
      from affected perimedullary veins to the extradural venous plexus as a potential
      alternate route for the venous hypertension to be released. CONCLUSIONS:
      Obstruction of the radicular venous outflow could be an important factor in
      inducing spinal congestive edema due to venous hypertension, as well as
      subsequent clinical symptoms of SDAVFs.

PMID- 22385083
TI  - Basilar artery thrombosis after reduction of cervical spondyloptosis: a
      cautionary report.
AB  - Traumatic cervical spondyloptosis is a rare clinical entity typically associated
      with complete neurological deficit. The inherent mechanics of this fracture
      dislocation pattern contorts the vertebral arteries in such a way that it may
      result in dissection or compromised flow through those vessels. Thus, intimal
      injury or thrombus from stasis of flow may result. Reduction of the
      spondyloptosis restores flow to the vertebral arteries, but it also may mobilize
      thrombus or propagate an intimal dissection within the previously contorted
      vessel.   The authors review their experience in the care of a 43-year-old man
      who sustained C4-5 spondyloptosis while riding an all-terrain vehicle. On
      arrival, the patient demonstrated no motor function below C-4 but had sensation
      to the nipple line (American Spinal Injury Association Spinal Cord Injury
      Classification B). The patient's cranial nerve examination was unremarkable.
      Computed tomography of the cervical spine demonstrated complete spondyloptosis at
      C4-5. The patient was immediately placed in cervical traction and taken to the
      operating room for open reduction of the fracture dislocation, decompression of
      the spinal cord, and stabilization with an interbody graft and cervical plate.
      Preoperative cervical traction was successful in only partial reduction of the
      fracture dislocation. Open reduction was achieved with exposure of the C-4 and C
      5 bodies and sequential distraction. After anatomical alignment was achieved, an
      interbody graft was placed and a cervical plate secured. A subsequent decline in
      the patient's level of consciousness prompted CT of the head, which showed
      evidence of a basilar artery thrombosis. A CT angiographic study demonstrated
      patency of the vertebral arteries, but a mid-basilar artery thrombosis. The
      patient progressed to brain death 24 hours after reduction of the fracture
      dislocation.   The degree of contortion of the vertebral arteries in cervical
      spondyloptosis in the upper cervical spine may result in stasis of flow with
      subsequent formation of thrombus or intimal injury. After anatomical reduction,
      restoration of flow within the vertebral arteries may mobilize the thrombus or
      propagate an intimal dissection and result in subsequent embolic events.
      Endovascular evaluation may be warranted immediately after anatomical reduction
      of a high cervical spondyloptosis for evaluation of the vertebral arteries and
      possible thrombus dissolution or retrieval.

PMID- 22385084
TI  - Nitrous oxide myelopathy posing as spinal cord injury.
AB  - The authors describe a patient who presented with acute tetraparesis and a
      proposed acute traumatic spinal cord injury that was the result of nitrous oxide
      myelopathy. This 19-year-old man sustained a traumatic fall off a 6-ft high wall.
      His examination was consistent with a central cord syndrome with the addition of
      dorsal column impairment. Cervical MRI demonstrated an isolated dorsal column
      signal that was suggestive of a nontraumatic etiology. The patient's symptoms
      resolved entirely over the course of 48 hours.   Nitrous oxide abuse is
      increasing in prevalence. Its toxic side effects can mask vitamin B12 and folate
      deficiency and central cord syndrome. The patient's history and radiographic
      presentation are key to establishing a diagnosis.

PMID- 22385085
TI  - Total motion generated in the unstable thoracolumbar spine during management of
      the typical trauma patient: a comparison of methods in a cadaver model.
AB  - OBJECT: The proper prehospital and inpatient management of patients with unstable
      spinal injuries is critical for prevention of secondary neurological compromise.
      The authors sought to analyze the amount of motion generated in the unstable
      thoracolumbar spine during various maneuvers and transfers that a trauma patient
      would typically be subjected to prior to definitive fixation. METHODS: Five fresh
      cadavers with surgically created unstable L-1 burst fractures were tested. The
      amount of angular motion between the T-12 and L-2 vertebral segments was measured
      using a 3D electromagnetic motion analysis device. A complete sequence of
      maneuvers and transfers was then performed that a patient would be expected to go
      through from the time of injury until surgical fixation. These maneuvers and
      transfers included spine board placement and removal, bed transfers, lateral
      therapy, and turning the patient prone onto the operating table. During each of
      these, the authors performed what they believed to be the most commonly used
      versus the best techniques for preventing undesirable motion at the injury level.
      RESULTS: When placing a spine board there was more motion in all 3 planes with
      the log-roll technique, and this difference reached statistical significance for
      axial rotation (p = 0.018) and lateral bending (p = 0.003). Using logrolling for
      spine board removal resulted in increased motion again, and this was
      statistically significant for flexion-extension (p = 0.014). During the bed
      transfer and lateral therapy, the log-roll technique resulted in more motion in
      all 3 planes (p <= 0.05). When turning the cadavers prone for surgery there was
      statistically more angular motion in each plane for manually turning the patient
      versus the Jackson table turn (p <= 0.01). The total motion was decreased by
      almost 50% in each plane when using an alternative to the log-roll techniques
      during the complete sequence (p <= 0.007). CONCLUSIONS: Although it is unknown
      how much motion in the unstable spine is necessary to cause secondary
      neurological injury, the accepted tenet is to minimize motion as much as
      possible. This study has demonstrated the angular motion incurred by the unstable
      thoracolumbar spine as experienced by the typical trauma patient from the field
      to positioning in the operating room using the best and most commonly used
      techniques. As previously reported, using the log-roll technique consistently
      results in unwanted motion at the injured spinal segment.

PMID- 22385086
TI  - Differences in pelvic parameters among Mexican, Caucasian, and Asian populations.
AB  - OBJECT: The aim of this study was to describe the pelvic parameters in a sample
      of healthy Mexican volunteers and to compare them with previously reported data
      for Caucasian and Asian populations. METHODS: This was a transversal study that
      included a sample population of healthy Mexican volunteers. Age, sex, and lateral
      radiographs of the lumbosacral region with the individual standing to obtain the
      pelvic parameters of pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI),
      and lumbar lordosis (LL) were recorded in each volunteer. The data were compared
      with those previously published for Caucasian and Asian individuals. RESULTS: In
      total, 202 Mexican individuals (81 men and 121 women; mean age 46.5 years, range
      18-85 years) were included. There were statistically significant differences
      between the Mexican and Caucasian control group with respect to PT (11.9 degrees 
      vs 15.78 degrees , respectively) and PI (51.91 degrees  vs 56.68 degrees ,
      respectively). Comparison with the Asian population showed statistically
      significant differences in relation to the Mexican group in terms of the PT (11.5
      degrees  vs 15.78 degrees ), PI (47.8 degrees  vs 56.68 degrees ), and SS (36.3
      degrees  vs 40.89 degrees ). The mean LL was 60.17 degrees  for the Mexican
      group, 52.3 degrees  for the Asian group, and 61.3 degrees  for the Caucasian
      group. A significant difference in LL was found between the Mexican and Asian
      populations (p < 0.0001). CONCLUSIONS: A comparison of the values for pelvic
      parameters and lumbar lordosis across the different population samples revealed
      statistically significant differences, which can be attributed to the ethnic
      origin of the individuals.

PMID- 22385087
TI  - Roots and wings.

PMID- 22385088
TI  - Fidelity of after-school program implementation targeting adolescent youth:
      identifying successful curricular and programmatic characteristics.
AB  - BACKGROUND: This study consisted of a formative evaluation of an after-school
      health education program designed for adolescent females, entitled Girls on
      Track. Evidence-based after-school programs have potential to supplement the
      traditional school day, encourage social and emotional skill development, improve
      the quality of student health, and contribute to a healthier school environment.
      Implementing comprehensive programs outside of the classroom, however, is
      challenging and gaps exist in the literature regarding implementation fidelity.
      METHODS: The national program was in a cohort of adolescent females from 11 Girls
      on Track locations in fall 2008 and 10 locations in spring 2009. Mixed-method
      analyses evaluated fidelity of lesson implementation, described curricular and
      programmatic characteristics associated with implementation fidelity, and
      assessed coach perceptions toward program quality and feasibility. RESULTS:
      Specific lesson characteristics associated with higher rates of implementation
      fidelity and favorable coach perceptions toward program feasibility included
      improved lesson clarity, more time to process health topics, teaching and
      learning objectives that were well aligned with lesson activities, incorporation
      of alternative activities for less-motivated participants, and provision of
      resources on key health topics for coaches. CONCLUSION: Girls on Track is
      currently being implemented across the United States and Canada, reaching over
      5000 adolescent females annually. Identifying and incorporating specific
      curricular and programmatic characteristics associated with high levels of
      implementation fidelity can enhance the quality and benefits of after-school
      programs.

PMID- 22385089
TI  - The effects of acculturation on healthy lifestyle characteristics among Hispanic
      fourth-grade children in Texas public schools, 2004-2005.
AB  - BACKGROUND: Childhood obesity is a national epidemic that disproportionately
      affects Hispanic children. Evidence suggests that increased acculturation among
      this population adversely affects diet and other healthy lifestyle
      characteristics, leading to higher rates of overweight and obesity. Healthy
      lifestyle characteristics must be understood in order to prevent or decrease
      overweight and obesity among Hispanic children. METHODS: Using the School
      Physical Activity and Nutrition (SPAN) study, we examined cross-sectional data on
      healthy lifestyle characteristics collected in Texas public schools from Hispanic
      fourth-grade children in 2004-2005. We calculated adjusted odds ratios and
      associated confidence intervals using multivariate logistic regression analyses
      to analyze the association between acculturation and healthy lifestyle
      characteristics among Spanish-speaking Hispanic children compared to English
      speaking Hispanic children. RESULTS: Spanish-speaking Hispanic boys consumed more
      milk and fruit than English-speaking Hispanic boys (milk: adjusted odds ratio
      [AOR]: 1.7, p = .02; fruit: AOR: 2.5, p = .0001). The likelihood that Spanish
      speaking Hispanic boys and girls did not know that there is a relationship
      between overweight and health problems were 2 times greater (boys: AOR: 1.7, p =
      .03; girls: AOR: 2.2, p = .006) than their English-speaking Hispanic
      counterparts. Likelihood of weight loss attempts was greater among Spanish
      speaking Hispanic boys than English-speaking Hispanic boys (AOR: 1.9, p = .04).
      CONCLUSIONS: Results are mixed. Lower levels of acculturation appear to be
      associated with both positive and negative healthy lifestyle characteristics,
      depending on sex. These findings have important implications for school health
      policies and programs and should be distributed to school administrators.

PMID- 22385090
TI  - An analysis of community use policies in Missouri school districts.
AB  - BACKGROUND: Joint use or community use policies are state-, district-, or school
      level policies that allow for shared use of space or facilities between a school
      and a city or private organization. For this study, we (1) created an inventory
      of community use policies within Missouri school districts; (2) analyzed the
      policies for content, and (3) identified district characteristics that predict
      the presence of a community use policy. METHODS: A coding tool was developed to
      assess the content of collected policies. Descriptors of 515 districts was
      gathered from the Missouri Department of Elementary and Secondary Education
      website. The policies were collected via district website or phone/e-mail contact
      and coded. Frequency of variables and a logistic regression to predict district
      presence of policy were computed. RESULTS: Of the 515 districts in Missouri, 375
      had a community use policy. Most (216) came from a policy template from the
      Missouri School Boards' Association or Missouri Consultants for Education (115).
      Only 42 districts had unique community use policies. Large or medium-sized
      districts were more likely to have a policy than small districts. Districts with
      higher percentage of students qualifying for free/reduced lunch were less likely
      to have a policy. CONCLUSION: Making changes to the 2 main resource templates
      have the potential to improve many district community use policies. Future
      efforts should focus on increasing policies and implementation in low resource
      and small districts. More research is needed on implementation and evaluation of
      community use policies.

PMID- 22385091
TI  - Return to play guidelines cannot solve the football-related concussion problem.
AB  - BACKGROUND: High school football players are the single largest cohort of
      athletes playing tackle football, and account for the majority of sport-related
      concussions. Return to play guidelines (RTPs) have emerged as the preferred
      approach for addressing the problem of sport-related concussion in youth
      athletes. METHODS: This article reviews evidence of the risks and effects of
      football-related concussion and subconcussive brain trauma, as well as the
      effectiveness of RTPs as a preventative measure. Literature review utilized
      PubMed and Google Scholar, using combinations of the search terms
      "football,""sports,""concussion,""Chronic Traumatic
      Encephalopathy,""athlete,""youth," and "pediatric." Literature review emphasized
      medical journals and primary neuroscientific research on sport-related concussion
      and concussion recovery, particularly in youth athletes. RESULTS: Sport-related
      concussion is a significant problem among student athletes. Student athletes are
      more vulnerable to concussion, and at risk of neurocognitive deficits lasting a
      year or more, with serious effects on academic and athletic performance. RTPs do
      little to address the problem of sport-related concussion or the chronic damage
      caused by subconcussive brain trauma. CONCLUSIONS: Emphasizing RTPs as the
      solution to the concussion problem in tackle football risks neglecting genuine
      reforms that would prevent concussions. More effective concussion prevention is
      needed. Eliminating tackling from school football for youth under 16 is
      recommended to reduce concussions. Additional modifications to football are
      recommended to enhance safety and reduce brain trauma at all levels of play.

PMID- 22385092
TI  - A conceptual model for training after-school program staffers to promote physical
      activity and nutrition.
AB  - BACKGROUND: After-school programs (ASPs, 3 pm to 6 pm) have been called upon to
      increase the amount of daily physical activity children accumulate and improve
      the nutritional quality of the snacks served. To this end, state and national
      physical activity and nutrition (PAaN) policies have been proposed. Frontline
      staff who directly interact with children on a daily basis are charged with the
      responsibility to meet policy goals. Without appropriate skills, staffers'
      ability to achieve such goals is limited. The gap between policies and
      improvements in PAaN must be bridged through professional development training.
      This article describes the development of an ASP staff professional development
      training program. METHODS: A systematic review was performed to identify relevant
      theoretical perspectives, empirical evidence, and recommended best practices
      relating to promoting PAaN of children. RESULTS: A comprehensive professional
      development framework was developed that incorporated the key elements identified
      from the review. These elements were distilled into 5 primary categories and
      conceptually referred to as the 5 Ms: mission-clearly defined policy/standards
      for PAaN; motivate-providing choices, developmentally appropriate activities,
      feedback, and encouragement; manage-structuring and managing the environment for
      safety, routines, and discipline; monitor-ongoing evaluation of PAaN; and
      maximize-incorporating all former Ms. CONCLUSIONS: The application of this
      training framework should lead to improved implementation and eventual
      achievement of policy goals for PAaN in ASPs. These competencies need to be
      developed in all ASPs if widespread improvements in PAaN within the ASP setting
      are to be realized.

PMID- 22385093
TI  - Boundin': responding to life challenges with resilience.

PMID- 22385095
TI  - Risk factors for surgical site infection after gastric surgery: a multicentre
      case-control study.
AB  - BACKGROUND: Surgical site infection (SSI) is a potentially morbid and costly
      complication of surgery. We conducted a multicentre case-control study to
      determine the risk factors for SSI in patients undergoing gastric surgery and to
      establish strategies to reduce the risk of SSI. METHODS: Between January 2007 and
      December 2008, 121 patients who developed an SSI after gastric surgery were
      matched with controls who had undergone surgery on the dates closest to those of
      the cases, at 13 centres in Korea. RESULTS: The results of multivariate analyses
      showed that the independent risk factors for SSI after gastric surgery were older
      age (p = 0.016), higher body mass index (BMI) (p = 0.033), male gender (p =
      0.047), and longer duration of prophylactic antibiotic use (p < 0.001).
      CONCLUSION: Older age, higher BMI, male gender, and longer duration of
      prophylactic antibiotic use were independently associated with significant
      increases in the risk of SSI. Additional prospective randomized studies are
      required to confirm these results.

PMID- 22385096
TI  - The relevance of patch testing in peristomal dermatitis.
AB  - BACKGROUND: Skin disorders are a common problem for ostomates, resulting in more
      than a third of visits to a stoma nurse. Irritant reactions, particularly
      irritant contact dermatitis, are the most frequently seen, accounting for > 50%
      of problems in some studies. OBJECTIVES: To report our experience in patch
      testing for peristomal dermatitis. METHODS: All patients were identified from our
      database of the skin-stoma clinic. Patch testing to various chemicals was
      performed and results analysed. RESULTS: From a total of 850 stoma patients in
      the combined clinic, 149 patients were patch tested. Only seven patients (4.7%)
      had positive reactions of current, proven relevance, none of which was related to
      constituents of the stoma appliances themselves. Most of the relevant allergens
      were preservatives and fragrances. CONCLUSIONS: The symptoms and clinical
      appearances of allergic contact dermatitis and irritant contact dermatitis are
      similar in the occluded peristomal environment and are therefore difficult to
      distinguish on clinical grounds alone. Allergy is a relatively infrequent cause
      of peristomal dermatitis despite the continual exposure of skin to the components
      of cleansers, medicaments, other accessories and the stoma bag systems
      themselves.

PMID- 22385098
TI  - The power of habits: unhealthy snacking behaviour is primarily predicted by habit
      strength.
AB  - OBJECTIVE: Although increasing evidence shows the importance of habits in
      explaining health behaviour, many studies still rely solely on predictors that
      emphasize the role of conscious intentions. The present study was designed to
      test the importance of habit strength in explaining unhealthy snacking behaviour
      in a large representative community sample (N= 1,103). To test our hypothesis
      that habits are crucial when explaining unhealthy snacking behaviour, their role
      was compared to the 'Power of Food', a related construct that addresses
      sensitivity to food cues in the environment. Moreover, the relation between Power
      of Food and unhealthy snacking habits was assessed. DESIGN AND METHODS: A
      prospective design was used to determine the impact of habits in relation to
      intention, Power of Food and a number of demographic variables. One month after
      filling out the questionnaire, including measures of habit strength and Power of
      Food, participants reported their unhealthy snacking behaviour by means of a 7
      day snack diary. RESULTS: Results showed that habit strength was the most
      important predictor, outperforming all other variables in explaining unhealthy
      snack intake. CONCLUSIONS: The findings demonstrate that snacking habits provide
      a unique contribution in explaining unhealthy snacking behaviour, stressing the
      importance of addressing habit strength in further research and interventions
      concerning unhealthy snacking behaviour.

PMID- 22385099
TI  - Inhibition of cytotoxicity by the Nhe cytotoxin of Bacillus cereus through the
      interaction of dodecyl maltoside with the NheB component.
AB  - Nhe ('nonhaemolytic enterotoxin') is a three-component cytotoxin implicated in
      the pathogenesis of diarrhoea by Bacillus cereus. Nhe forms pores in pure lipid
      bilayers, but the function of the individual components (NheA, NheB and NheC)
      remains unclear. NheB and NheC are structural homologues of ClyA, a pore-forming
      cytotoxin of Escherichia coli. The non-ionic detergent dodecyl maltoside (DDM)
      has been shown to inhibit haemolysis of ClyA. We used DDM as a probe to examine
      the response of the Nhe proteins to DDM micelles. At its critical micellar
      concentration (0.2 mM), DDM inhibited propidium uptake by the native Nhe complex
      in Vero and HT29 cell suspensions. Pre-incubation of NheC with DDM did not
      inhibit cytotoxicity. NheB exhibited marked changes in 1-anilinonaphthalene-8
      sulphonic acid (ANS) fluorescence after pre-exposure to DDM. Pre-incubation of
      NheB with DDM resulted in large molecular weight complexes as detected by size
      exclusion chromatography and diffusion through sized dialysis membranes and
      prevented binding of NheB to Vero cell monolayers. These data support a model in
      which conformational changes and oligomerization of NheB are prerequisite events
      in the process of pore formation.

PMID- 22385097
TI  - Methylome of fetal and maternal monocytes and macrophages at the feto-maternal
      interface.
AB  - PROBLEM: Decidual macrophages (dMphi) of the mother and placental macrophages
      (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto
      maternal interface. This study was conducted to compare the DNA methylome of
      maternal and fetal monocytes, dMphi, and HC and thereby to determine the
      immunobiological importance of DNA methylation in pregnancy. METHOD OF STUDY:
      Paired samples were obtained from normal pregnant women at term not in labor and
      their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated
      from the peripheral blood of mothers and fetal cord blood, respectively. dMphi
      and HC were obtained from the decidua of fetal membranes and placentas,
      respectively. DNA methylation profiling was performed using the Illumina Infinium
      Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were
      performed for validation experiments. RESULTS: (i) Significant differences in DNA
      methylation were found in each comparison (MMo versus FMo, 65 loci; dMphi versus
      HC, 266 loci; MMo versus dMphi, 199 loci; FMo versus HC, 1030 loci). (ii) Many of
      the immune response-related genes were hypermethylated in fetal cells (FMo and
      HC) compared to maternal cells (MMo and dMphi). (iii) Genes encoding markers of
      classical macrophage activation were hypermethylated, and genes encoding
      alternative macrophage activation were hypomethylated in dMphi and HC compared to
      MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B
      were significantly lower in dMphi than in HC. (v) 5-azacytidine treatment
      increased expression of INCA1 in dMphi. CONCLUSIONS: The findings herein indicate
      that DNA methylation patterns change during monocyte-macrophage differentiation
      at the feto-maternal interface. It is also suggested that DNA methylation is an
      important component of the biological machinery conferring an anti-inflammatory
      phenotype to macrophages at the feto-maternal interface.

PMID- 22385100
TI  - Molecular characterization of dissolved organic matter in glacial ice: coupling
      natural abundance 1H NMR and fluorescence spectroscopy.
AB  - Glaciers and ice sheets are the second largest freshwater reservoir in the global
      hydrologic cycle, and the onset of global climate warming has necessitated an
      assessment of their contributions to sea-level rise and the potential release of
      nutrients to nearby aquatic environments. In particular, the release of dissolved
      organic matter (DOM) from glacier melt could stimulate microbial activity in both
      glacial ecosystems and adjacent watersheds, but this would largely depend on the
      composition of the material released. Using fluorescence and (1)H NMR
      spectroscopy, we characterize DOM at its natural abundance in unaltered samples
      from a number of glaciers that differ in geographic location, thermal regime, and
      sample depth. Parallel factor analysis (PARAFAC) modeling of DOM fluorophores
      identifies components in the ice that are predominantly proteinaceous in
      character, while (1)H NMR spectroscopy reveals a mixture of small molecules that
      likely originate from native microbes. Spectrofluorescence also reveals a
      terrestrial contribution that was below the detection limits of NMR; however,
      (1)H nuclei from levoglucosan was identified in Arctic glacier ice samples. This
      study suggests that the bulk of the DOM from these glaciers is a mixture of
      biologically labile molecules derived from microbes.

PMID- 22385103
TI  - Direct observation of inhomogeneous solid electrolyte interphase on MnO anode
      with atomic force microscopy and spectroscopy.
AB  - Solid electrolyte interphase (SEI) is an in situ formed thin coating on lithium
      ion battery (LIB) electrodes. The mechanical property of SEI largely defines the
      cycling performance and the safety of LIBs but has been rarely investigated.
      Here, we report quantitatively the Young's modulus of SEI films on MnO anodes.
      The inhomogeneity of SEI film in morphology, structure, and mechanical properties
      provides new insights to the evolution of SEI on electrodes. Furthermore, the
      quantitative methodology established in this study opens a new approach to direct
      investigation of SEI properties in various electrode materials systems.

PMID- 22385102
TI  - Combination peel with incorporated fractional prickle coral calcium for the
      treatment of keratosis pilaris: a pilot study.
AB  - BACKGROUND: Keratosis pilaris (KP) is a common condition of follicular plugging
      with variable erythema. There is a lack of reliable response to the treatment of
      KP. OBJECTIVE: We evaluated the effect and safety of combination peel with
      fractional prickle coral calcium (FCRTM) in the treatment of KP. MATERIALS AND
      METHODS: Sixteen Korean patients were treated with FCRTM on both upper arms for
      five sessions at 2-week intervals. Clinical evaluations, mexameter measurements,
      and assessment of patients' satisfaction and adverse events were performed at
      baseline and every visit. RESULTS: After treatments, statistically significant
      improvements in the baseline KP were observed in erythema and melanin index of
      mexameter on treated upper arms. Both the physicians' and patients' assessments
      correlate with the results of mexameter scores. CONCLUSION: Our results suggest
      FCRTM should be considered as an effective and safe treatment option for the
      patients with KP.

PMID- 22385104
TI  - Altered expression of melanocortin-1 receptor (MC1R) in a yellow-coloured wild
      raccoon dog (Nyctereutes procyonoides).
AB  - BACKGROUND: The melanocortin 1 receptor (MC1R) gene plays a key role in
      determining coat colour in mammals by controlling the proportion of eumelanin and
      pheomelanin granules. Wild raccoon dogs have a mixed coat colour, with black to
      brown and grey hairs. HYPOTHESIS/OBJECTIVES: The study was performed to identify
      the cause of the variant yellow coat colour in a wild raccoon dog. ANIMALS: A
      wild raccoon dog that showed coat colour change to yellow and four wild-type
      raccoon dogs that showed normal coat colour were included. METHODS: To identify
      the cause of the variant yellow coat colour, we examined the sequence of the MC1R
      gene and its expression at the mRNA and protein levels. RESULTS: The coding
      region of the MC1R gene of this raccoon dog comprised 954 bp, the same as for
      wild-type raccoon dogs and domestic dogs. By comparing the gene with that in the
      wild-type raccoon dog, a 2 bp deletion was detected in the 5'-untranslated
      region, positioned 152 bp upstream of the start codon. However, there was no
      significant difference in the mRNA expression level. The yellow raccoon dog
      revealed a significantly decreased MC1R protein level compared with the wild-type
      raccoon dogs, indicating an increase in pheomelanin synthesis. CONCLUSIONS AND
      CLINICAL IMPORTANCE: These results suggest that the variant coat colour in the
      yellow raccoon dog was associated with decreased MC1R function.

PMID- 22385105
TI  - Racial differences in the association between gestational diabetes mellitus and
      risk of type 2 diabetes.
AB  - BACKGROUND: It is recognized that a history of gestational diabetes mellitus
      (GDM) predicts incident type 2 diabetes in women. However, it is unclear if there
      is a racial disparity between the association of GDM and type 2 diabetes.
      METHODS: We studied 1,142 women with a history of GDM and 18,856 women without a
      history of GDM aged 13-50 years with their first record of pregnancy in Louisiana
      State University Hospital-Based Longitudinal Study database between 1990 and
      2009. History of GDM was used to predict incident type 2 diabetes. RESULTS:
      During a mean follow-up of 8.6 years, 1,394 women developed type 2 diabetes. The
      multivariable adjusted hazard ratio (HR) of type 2 diabetes was 6.52 (95%
      confidence interval [CI] 5.73-7.43) among women with GDM compared to women
      without GDM. Stratification by age, race, and body mass index (BMI) gave similar
      results. Compared with African American and white women without a history of GDM,
      the relative risk for type 2 diabetes was higher in African American women than
      in white women with a history of GDM. Compared with non-GDM women compartments,
      GDM women after delivery for <1, 1.0-3.9, 4.0-5.9, 6.0-7.9, 8-9.9, and >=10.0
      years had 4.00, 5.44, 4.26, 3.16, 4.49, and 4.17 times higher risk of having type
      2 diabetes, respectively. CONCLUSIONS: A history of GDM is a strong predictor of
      subsequent type 2 diabetes among Louisiana women, especially among African
      American women.

PMID- 22385106
TI  - Resemblance and investment in children.
AB  - According to evolutionary explanations men hardly ever are absolutely certain
      about their biological fatherhood therefore they must seek various sources of
      information to subjectively establish whether they are the genetic fathers of the
      children they raise. Apicella and Marlowe (2004) showed that fathers who
      perceived greater similarity between their children and themselves were willing
      to invest more resources (e.g., time, money, care) in their offspring presumably
      because the perceived resemblance indicated to the fathers their genetic
      relatedness with their children. The present study extended the design of
      Apicella and Marlowe's original study and included both fathers and mothers as
      participants. Parents were recruited by a female confederate at the airport and
      at the railway station in Wroclaw (Poland). Multiple regression analyses showed
      that perceived resemblance predicted parental investment in the child for both
      men and women. The fact that mothers' declarations of investment in their
      children also depended on the perceived resemblance factor is not consistent with
      evolutionary formulations delineated by Apicella and Marlowe (2004; 2007). Future
      studies must resolve the issue of whether the resemblance-investment relation in
      fathers results from men relaying on child's resemblance to themselves as an
      indicator of their own biological paternity, or whether it results from the more
      parsimonious phenomenon that people in general are attracted more to other people
      who are similar to them. 

PMID- 22385107
TI  - "Crocodile"--new dangerous designer drug of abuse from the East.

PMID- 22385108
TI  - On local search for bi-objective knapsack problems.
AB  - In this article, a local search approach is proposed for three variants of the bi
      objective binary knapsack problem, with the aim of maximizing the total profit
      and minimizing the total weight. First, an experimental study on a given
      structural property of connectedness of the efficient set is conducted. Based on
      this property, a local search algorithm is proposed and its performance is
      compared to exact algorithms in terms of runtime and quality metrics. The
      experimental results indicate that this simple local search algorithm is able to
      find a representative set of optimal solutions in most of the cases, and in much
      less time than exact algorithms.

PMID- 22385109
TI  - The C-terminal extension of chloroplast 2-Cys peroxiredoxin is critical for
      interaction with ATP.
AB  - 2-Cys peroxiredoxins (2-Cys Prxs) are ubiquitous enzymes that have been
      implicated in peroxide-mediated signaling of markedly different processes, such
      as cancer and photosynthesis. A highly conserved C-terminal extension of
      eukaryotic homologues modulates both the overoxidation of cysteines and the
      formation of oligomers. Here, we reveal that the plant counterpart regulates the
      self-polymerization of 2-Cys Prx triggered by ATP and Mg(2+). This feature is of
      particular importance under oxidative stress because the interaction of ATP with
      2-Cys Prx rapidly integrates nonredox chemistry of signaling pathways into a
      network hub governed by multiple redox transformations at cysteine residues.

PMID- 22385110
TI  - Body composition, bone mineral density and fractures in late postmenopausal women
      with polycystic ovary syndrome - a long-term follow-up study.
AB  - OBJECTIVE: Hyperandrogenism is one of the characteristic features of the
      polycystic ovary syndrome (PCOS). Androgens are important for bone mass. Studies
      on bone mineral density (BMD) and fractures in postmenopausal women with PCOS are
      lacking. The aim of this study was to investigate whether postmenopausal women
      with PCOS differ from controls regarding body composition, BMD and prevalence of
      fractures, and to compare women with PCOS with controls regarding correlations
      between total BMD and sex hormones. DESIGN: A prospective 21-year follow-up
      study. Anthropometry, hormonal measurements and questionnaires were performed in
      1987 and in 2008. Fractures were X-ray-verified. BMD measurements were taken in
      1992, using single-photon absorptiometry (SPA), and in 2008, using dual-energy X
      ray absorptiometry (DXA), to also enable measurements of body composition.
      PATIENTS: Twenty-five women with PCOS (Rotterdam criteria), aged 61-78 years, and
      68 randomly allocated age-matched controls. MEASUREMENTS: Body composition, BMD,
      fractures and sex steroids. RESULTS: At follow-up, the postmenopausal women with
      PCOS maintained a higher free androgen index (FAI), but had similar body fat,
      lean mass and BMD compared with controls. The hip circumference increased only in
      women with PCOS (P < 0.01), during follow-up. The fracture incidence was similar
      to that of controls (56% vs 41%, ns). In the controls, total BMD was positively
      correlated with oestradiol (R = 0.322, P < 0.01) and FAI (R = 0.307, P < 0.05)
      and negatively correlated with SHBG (R = -0.429, P < 0.001), but not in the women
      with PCOS. CONCLUSIONS: Postmenopausal women with PCOS with persistently higher
      FAI had similar muscle mass, BMD and fracture incidence as controls during this
      long-term follow-up.

PMID- 22385111
TI  - Inappropriate ICD shocks caused by T-wave oversensing due to acute alcohol
      intoxication.
AB  - T-wave oversensing can be a serious problem that often results in inappropriate
      device therapy. We report here a patient with binge alcohol use who received
      multiple, inappropriate ICD shocks due to T-wave oversensing from repolarization
      changes induced by acute alcohol intoxication and no other relevant metabolic
      derangements. Following recovery from his alcohol intoxication a few days later,
      the T-wave amplitude decreased so the device no longer inappropriately sensed or
      delivered therapies. This case represents an uncommon, but reversible, cause of T
      wave oversensing that should be considered before more aggressive measures are
      taken to correct the abnormality.

PMID- 22385112
TI  - Repertoire of gluten peptides active in celiac disease patients: perspectives for
      translational therapeutic applications.
AB  - Celiac disease is a common and lifelong food intolerance, affecting approximately
      1% of the population. Because of a mechanism not completely understood, the
      ingestion of wheat gluten, and of homologue proteins of barley and rye, induces
      in genetically predisposed individuals pronounced inflammatory reactions mainly
      at the site of small intestine. Gluten, the triggering factor, is a complex
      protein mixture highly resistant to the gastrointestinal enzymatic proteolysis,
      and this results in the presence of large, and potentially immunogenic, peptides
      at the intestinal mucosa surface. During the last decade, several studies have
      defined gluten peptides able to stimulate adaptive T cells, of either CD4 or CD8
      phenotype, and to activate innate (non T) immune cells. This review examines the
      complete repertoire of gluten peptides recognized by celiac T cells and discusses
      the several translational implications that the identification of these epitopes
      opens.

PMID- 22385113
TI  - Cancer cachexia: molecular targets and pathways for diagnosis and drug
      intervention.
AB  - Cancer cachexia is a highly debilitating paraneoplastic disease observed in more
      than 50% of patients with advanced cancers and directly contributes to 20% of
      cancer deaths. Skeletal muscle wasting is a prominent feature of the disease and
      is believed to result from the loss of balance between protein synthesis and
      degradation. Quality of life and prognosis are severely compromised in patients
      with cancer cachexia. Despite current knowledge on the mediators involved in
      cancer cachexia, treatment targeting a single molecule has rendered limited
      effectiveness. This article aims to review the mediators of cancer cachexia and
      interventions attempted in the literature and discuss the common pathways leading
      to protein loss that these mediators modulate during cachexia. We believe that by
      targeting downstream effectors that are common in these pathways, a better
      therapeutic approach to reverse muscle wasting and maintain muscle function
      during cancer cachexia will be achieved.

PMID- 22385114
TI  - Glycerolipid acyltransferases in triglyceride metabolism and energy homeostasis
      potential as drug targets.
AB  - Glycerolipid acyltransfereases play important roles in physiological and
      pathophysiological processes of triglyceride (TAG) metabolism and energy balance.
      Glycerol-3-phosphate acyltransferases (GPATs) are key enzymes in the triglyceride
      biosynthetic pathway. In addition to the mitochondrial GPAT1 that was first
      cloned and studied, novel microsomal enzyme isoforms have been discovered in
      recent years. The potential function of one of the GPATs, GPAT4, was studied in
      GPAT4 deficient mice that suggested its role in TAG synthesis in multiple
      tissues. Monoacylglycerol and diacylglycerol acyltransferases (MGAT2 and DGAT1)
      are important enzymes involved in intestinal triglyceride absorption, and studies
      in recent years from knockout mice have revealed their important role in whole
      body energy metabolism through changes in intestinal TAG absorption kinetics.
      Both MGAT2 and DGAT1 mice are resistant to dietinduced obesity and have improved
      insulin sensitivity and hepatic TAG accumulation. These data suggest that these
      enzymes are intimately involved in TAG metabolism and whole body energy
      homeostasis and that inhibition of these enzymes may provide therapeutic benefits
      for metabolic disorders such as obesity, metabolic syndrome, and type 2 diabetes.

PMID- 22385115
TI  - Evaluation of specific immune responses to BoNT/A and tetanus toxoid in patients
      undergoing treatment for neurologic disorders.
AB  - Botulinum neurotoxins (BoNTs) are used in the treatment of many neurological
      disorders. The primary structure of BoNTs shows a high degree of homology with
      the tetanus neurotoxin, the toxoid of which is used as a vaccine. Because of the
      potential cross-reactivity between these toxins, we investigated the effects of
      Botulinum neurotoxin A (BoNT/A) and tetanus toxoid on peripheral blood
      mononuclear cells (PBMC) and the corresponding serum antibody levels, in twenty
      patients who had been treated with BoNT/A. We observed very low PBMC
      immunostimulation by BoNT/A at the tested dose (15 units/ml), as demonstrated by
      the low lymphocyte proliferation, and the absence of detectable antibodies cross
      reacting with tetanus. However, exposure of PBMC from tetanus-sensitized patients
      to both neurotoxins showed that BoNT/A exerted a co stimulatory effect on tetanus
      stimulated cells. Interestingly, in flow cytometry analysis, BoNT/A seemed to
      also alter the ratio of naive (CD45RA) : memory/effector (CD45RO) T lymphocyte
      subsets, in favour of CD45RO. These preliminary data give a new insight on the
      potential immune crossreactivity between the two antigens. In view of the wide
      use of both neurotoxins, these immunotoxic effects merit a more detailed
      investigation.

PMID- 22385116
TI  - The role of bacterial lipopolysaccharides as immune modulator in vaccine and drug
      development.
AB  - Bacterial lipopolysaccharide (LPS, endotoxin) is the major constituent of the
      outer membrane of Gram-negative bacteria. LPS can cause a variety of immune- and
      cellular disorders that lead to lethal effects and clinical manifestations of
      infectious diseases. Several molecular and cellular in vitro techniques, besides
      synthesis of analogous molecules of the LPS active region, have provided insight
      in the molecular mechanisms of LPS bioactivity in cellular systems. These
      advances have facilitated the application of diverse LPS-based molecules in
      relevant areas such as vaccine technology, allergen immunotherapy, treatment of
      immune-related diseases/disorders, LPS-related inflammatory processes and sepsis.
      The purpose of this review is to examine the progress in the generation of new
      LPS-based molecules and their therapeutic potential.

PMID- 22385117
TI  - Subclinical hypothyroidism and cognitive dysfunction in the elderly.
AB  - While overt hypothyroidism is associated with reversible dementia in the elderly,
      the relationship of subclinical hypothyroidism with cognition remains a
      controversial issue. Our aim was to investigate the correlation between
      subclinical hypothyroidism and cognition in the elderly, with particular
      reference to long term memory and selective attention. We selected 337
      outpatients (177 men and 160 women), mean age 74.3 years, excluding the subjects
      with thyroid dysfunction and those treated with drugs influencing thyroid
      function. The score of Mini Mental State Examination (MMSE) was significantly
      lower in the group of patients with subclinical hypothyroidism than in euthyroid
      subjects (p<0.03). It was observed that patients with subclinical hypothyroidism
      had a probability about 2 times greater (RR = 2.028, p<0.05) of developing
      cognitive impairment. Prose Memory Test (PMT) score resulted significantly lower
      in subjects with subclinical hypothyroidism (p<0.04). Considering the Matrix Test
      (MT) score, the performance was slightly reduced in subclinical hypothyroidism
      (NS). Furthermore, TSH was negatively correlated with MMSE (p<0.04), PMT (p<0.05)
      and MT score (NS). No correlation was found between FT4 and FT3 and MMSE, PMT and
      MT score. In the elderly, subclinical hypothyroidism is associated with cognitive
      impairment, and its impact on specific aspects of cognition (long term memory and
      selective attention) is less evident.

PMID- 22385119
TI  - Homeobox C5 expression is associated with the progression of 4-nitroquinoline 1
      oxide-induced rat tongue carcinogenesis.
AB  - BACKGROUND: Aberrant expression of homeobox genes (HOX), normally required for
      the differentiation of a particular tissue, has been reported in several types of
      cancer, but poorly addressed in oral squamous cell carcinoma (OSCC). The present
      study investigated the expression of HOXC5 in OSCC and identified molecular
      biomarker whose expression is associated with the multistep oral carcinogenesis.
      METHODS: The expression of HOXC5, proliferation cell nuclear antigen (PCNA), and
      Bcl-2 was examined by RT-PCR and Western blot analysis and confirmed by
      immunohistochemistry and transferase-mediated dUTP nick end-labeling (TUNEL)
      assay in a 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis
      model. RESULTS: Homeobox genes C5 was overexpressed in SCC tissues, but not in
      normal tissues by RT-PCR and Western blot analysis. Along with the progress of
      multistep carcinogenesis, the levels of HOXC5 expression of mRNA and protein
      significantly increased during the dysplasia (moderate to severe dysplasia) when
      compared with normal and hyperplasia. The levels of PCNA and Bcl-2 were
      sequentially increased from hyperplasia to dysplasia and SCC. By
      immunohistochemistry, HOXC5 expression was significantly increased in dysplasia,
      whereas PCNA expression was gradually increased during tongue carcinogenesis.
      TUNEL-positive cells were increased until dysplasia, but reduced in SCC.
      CONCLUSIONS: These results indicate that overexpression of HOXC5 is correlated
      with oral carcinogenesis and strongly contributed to the development of OSCC.
      HOXC5 may be a useful biomarker and has an emerging therapeutic target of OSCC.

PMID- 22385118
TI  - Effectiveness of gonadotropin administration for spermatogenesis induction in
      hypogonadotropic hypogonadism: a possible role of androgen receptor CAG repeat
      polymorphism and therapeutic measures.
AB  - Prepuberal-onset (PRHH) and postpuberal-onset (PSHH) Hypogonadotropic Hypogondism
      (HH) refer to a heterogeneous group of patients, showing a broad spectrum of
      clinical signs and symptoms of androgen deficiency in consideration of the
      different possible aetiologies and the age at onset. These patients, though,
      required Gonadotropin treatment (GnTh) by means of administration of both the
      beta Human Chorionic Gonodadotropin (beta HCG) and the Follicle Stimulating
      Hormone (FSH) to obtain mature sperms in the ejaculate aiming to reach fertility
      levels. However, the response to GnTh is always unpredictable concerning either
      the effectiveness or the duration of the therapy. Consequently, different studies
      have been carried out to identify clinical (i.e. cryptorchidism, gynecomastia,
      testis size, etc) and biochemical markers [serum Testosterone (T) and Inhibin B
      (IB)] that can be useful to predict the effectiveness of GnTh. Given that the
      actions of T, even those directed at inducing and maintaining spermatogenesis,
      are mediated by its interaction with the Androgen Receptor (AR), we measured the
      AR CAG repeat polymorphism in men with HH, in order to examine whether the CAG
      polymorphism extensions could co-regulate the GnTh effectiveness. Twenty-three HH
      subjects were subdivided according to the age at onset (pre- and postpubertal)
      and treated with the same scheme and doses of GnTh, extending the period of
      treatment up to 30 months. Thirty-five healthy and fertile men served as a
      control group (CG). Twelve HH subjects (3 PRHH and 9 PSHH), who reached complete
      spermatogenesis within 12 months, showed the length of AR CAG repeat number [20
      (19-23) = median (interquartile range 25th - 75th percentile)] not statistically
      different from our CG [20 (19-22)], while CAG repeat number [23 (20-25)] of 11 HH
      patients (9 PRHH and 2 PSHH) who obtained mature sperms in their ejaculate beyond
      a year to within 30 months, was significantly higher. Our results suggest that
      the length of AR CAG repeat polymorphism might affect the response to GnTh in men
      suffering from HH, in particular in those patients with prepubertal-onset
      hypogonadism.

PMID- 22385120
TI  - Cocaine esterase-cocaine binding process and the free energy profiles by
      molecular dynamics and potential of mean force simulations.
AB  - The combined molecular dynamics (MD) and potential of mean force (PMF)
      simulations have been performed to determine the free energy profiles for the
      binding process of (-)-cocaine interacting with wild-type cocaine esterase (CocE)
      and its mutants (T172R/G173Q and L119A/L169K/G173Q). According to the MD
      simulations, the general protein-(-)-cocaine binding mode is not affected by the
      mutations; e.g.. the benzoyl group of (-)-cocaine is always bound in a subsite
      composed of aromatic residues W151, W166, F261, and F408 and hydrophobic residue
      L407, while the carbonyl oxygen on the benzoyl group of (-)-cocaine is hydrogen
      bonded with the oxyanion-hole residues Y44 and Y118. According to the PMF
      calculated free energy profiles for the binding process, the binding free
      energies for (-)-cocaine with the wild-type, T172R/G173Q, and L119A/L169K/G173Q
      CocEs are predicted to be -6.4, -6.2, and -5.0 kcal/mol, respectively. The
      computational predictions are supported by experimental kinetic data, as the
      calculated binding free energies are in good agreement with the experimentally
      derived binding free energies, i.e., -7.2, -6.7, and -4.8 kcal/mol for the wild
      type, T172R/G173Q, and L119A/L169K/G173Q, respectively. The reasonable agreement
      between the computational and experimental data suggests that the PMF simulations
      may be used as a valuable tool in new CocE mutant design that aims to decrease
      the Michaelis-Menten constant of the enzyme for (-)-cocaine.

PMID- 22385121
TI  - Treatment of scabies: Comparison of permethrin 5% versus ivermectin.
AB  - Scabies is an ectoparasitic, highly contagious skin disease caused by a mite
      called Sarcoptes scabiei. The insecticides ivermectin and permethrin are commonly
      used for treatment of scabies. This study aimed at comparing the efficacy of oral
      ivermectin with topical permethrin in treating scabies. Two hundred and forty-two
      patients with scabies attending the dermatology outpatient department of Sina
      Hospital, Tabriz University of Medical Sciences were admitted. Patients were
      divided into two groups randomly. The first group and their family contacts
      received 5% permethrin cream and the other received oral ivermectin. Treatment
      was evaluated at intervals of 2 and 4 weeks. A single dose of ivermectin provided
      a cure rate of 85.9% at a 2-week interval, which increased to 100% after crossing
      over to the permethrin group at a 4-week interval. Twice application of
      permethrin with a 1-week interval was effective in 92.5% of patients, which
      increased to 94.2% after crossing over to the ivermectin group at a 4-week
      interval. Permethrin-treated patients recovered earlier. Twice application of
      permethrin with a 1-week interval is superior to a single dose of ivermectin. The
      temporal dissociation in clinical response suggests that ivermectin may not be
      effective against all the stages in the life cycle of the parasite.

PMID- 22385122
TI  - Air-water partitioning of 222Rn and its dependence on water temperature and
      salinity.
AB  - Radon is useful as a tracer of certain geophysical processes in marine and
      aquatic environments. Recent applications include detection of groundwater
      discharges into surface waters and assessment of air/sea gas piston velocities.
      Much of the research performed in the past decade has relied on continuous
      measurements made in the field using a radon stripping unit connected to a radon
      in-air detection system. This approach assumes that chemical equilibrium is
      attained between the water and gas phases and that the resulting air activity can
      be multiplied by a partition coefficient to obtain the corresponding radon-in
      water activity. We report here the results of a series of laboratory experiments
      that describes the dependence of the partition coefficient upon both water
      temperature and salinity. Our results show that the temperature dependence for
      freshwater closely matches results that were previously available. The salinity
      effect, however, has largely been ignored and our results show that this can
      result in an overestimation of radon concentrations, especially in cooler, more
      saline waters. Related overestimates in typical situations range between 10
      (warmer less saline waters) and 20% (cooler, more saline waters).

PMID- 22385123
TI  - Skin involvement in Down syndrome transient abnormal myelopoiesis.

PMID- 22385124
TI  - Nonmelanoma skin cancer treatment training varies across different medical
      specialists.
AB  - BACKGROUND: Physicians from various specialties treat patients with nonmelanoma
      skin cancer (NMSC). The isolation of specialties from each other may result in
      different approaches to skin cancer training. PURPOSE: Our purpose was to
      determine the type and amount of NMSC surgical training that is received during
      dermatology, general surgery, internal medicine, otolaryngology, and plastic
      surgery residencies. METHODS: E-mail contact information for residency program
      directors of all accredited programs in each specialty was compiled through the
      American Medical Association's online residency database. A total of 920
      residency program directors were emailed surveys concerning the training of
      residents in the treatment of NMSC. RESULTS: Forty-two of 920 surveys were
      returned. All surveyed specialty groups, except internal medicine, had training
      in NMSC treatment including simple excision, split thickness skin grafts, and
      tissue rearrangement. A majority of the dermatology and plastic surgery programs
      instruct their residents in Mohs micrographic surgery and full thickness skin
      grafts. Electrodessication and curettage was most often instructed in
      dermatology, general surgery, and plastic surgery programs. CONCLUSION: Greater
      consistency in NMSC treatment training may be beneficial. Because different
      approaches may be best suited to particular clinical situations, NMSC treatment
      training should include adequate exposure to all NMSC treatment techniques.

PMID- 22385125
TI  - A waterborne outbreak with a single clone of Campylobacter jejuni in the Danish
      town of Koge in May 2010.
AB  - BACKGROUND: In Denmark, large-scale waterborne outbreaks are rare. This report
      describes the investigation of an outbreak that occurred in the town of Koge in
      May 2010. METHODS: The epidemiological investigation consisted of hypothesis
      generating telephone interviews, followed by a cohort study among approximately
      20,000 residents using an online questionnaire. Odds ratios were calculated for
      exposures including the number of glasses of tap water consumed. Geographical
      spreading was assessed using a geographical information system. The
      microbiological investigation included cultures of stool samples and flagellin
      typing. In the environmental investigation, water samples were tested for
      Escherichia coli and coliform counts and for DNA of Campylobacter, Enterococcus,
      and Bacteroides. During the outbreak investigation a water boiling order was
      enforced, as tap water was considered a potential source. RESULTS: Of 45 patients
      with laboratory confirmed Campylobacter infection in the municipality of Koge in
      May, 43 lived in the area covered by the central water supply. Of 61 patients
      with laboratory confirmed Campylobacter jejuni by 8 June, 50 shared a common
      flagellin gene type--flaA type 36 (82%). The epidemic curve from the cohort study
      showed a wave of diarrhoea onset from 14 to 20 May (n = 176). Among these
      patients, the development of diarrhoea was associated with drinking tap water
      with a dose-response pattern (linear increase by 2 glasses: odds ratio 1.40, 95%
      confidence interval 1.16-1.70). No bacterial DNA was found in water samples.
      CONCLUSIONS: These findings indicated a point source contamination of tap water
      with a single clone of C. jejuni which likely occurred on 12-13 May. The water
      boiling order was lifted on 18 June.

PMID- 22385126
TI  - A bioinformatics approach to preterm birth.
AB  - A vast body of literature has suggested genetic programming of preterm birth.
      However, there is a complete lack of an organized analysis and stratification of
      genetic variants that may indeed be involved in the pathogenesis of preterm
      birth. We developed a novel bioinformatics approach to identify the nominal
      genetic variants associated with preterm birth. We used semantic data mining to
      extract all published articles related to preterm birth. Genes identified from
      public databases and archives of expression arrays were aggregated with genes
      curated from the literature. Pathway analysis was used to impute genes from
      pathways identified in the curations. The curated articles and collected genetic
      information are available in a web-based tool, the database for preterm birth
      (dbPTB) that forms a unique resource for investigators interested in preterm
      birth.

PMID- 22385127
TI  - Light-induced retinal degeneration is prevented by zinc, a component in the age
      related eye disease study formulation.
AB  - Mineral supplements are often included in multivitamin preparations because of
      their beneficial effects on metabolism. In this study, we used an animal model of
      light-induced retinal degeneration to test for photoreceptor cell protection by
      the essential trace element zinc. Rats were treated with various doses of zinc
      oxide and then exposed to intense visible light for as long as 8 h. Zinc
      treatment effectively prevented retinal light damage as determined by rhodopsin
      and retinal DNA recovery, histology and electrophoretic analysis of DNA damage
      and oxidized retinal proteins. Zinc oxide was particularly effective when given
      before light exposure and at doses two- to four-fold higher than recommended by
      the age-related eye disease study group. Treated rats exhibited higher serum and
      retinal pigment epithelial zinc levels and an altered retinal gene expression
      profile. Using an Ingenuity database, 512 genes with known functional annotations
      were found to be responsive to zinc supplementation, with 45% of these falling
      into a network related to cellular growth, proliferation, cell cycle and death.
      Although these data suggest an integrated and extensive regulatory response, zinc
      induced changes in gene expression also appear to enhance antioxidative capacity
      in retina and reduce oxidative damage arising from intense light exposure.

PMID- 22385128
TI  - Relationship of sex hormones and nocturia in lower urinary tract symptoms induced
      by benign prostatic hyperplasia.
AB  - OBJECTIVE: The study sought to clarify the relationship between sex hormone
      levels and lower urinary tract symptoms (LUTS) in patients with benign prostate
      hyperplasia. METHODS: Between 2007 and 2010, serum total testosterone (TT), free
      testosterone, and estradiol were prospectively measured in patients who were
      transferred to our university hospital. The 924 subjects were divided into two
      groups. Group I (n = 646) were treated with an alpha blocker only and group II (n
      = 278) were treated with an alpha blocker + a 5-alpha reductase inhibitor over 3
      months before their visit. Clinical conditions were assessed by digital rectal
      examination, prostate-specific antigen, International Prostate Symptom Score
      (IPSS), transrectal ultrasonography and maximum urinary flow rate and postvoid
      residual urine. RESULTS: The mean age was 69.65 +/- 6.56 years. The total IPSS
      and subscore (storage symptom) was significantly associated with age (p < 0.001/p
      < 0.05) and the TT level (p < 0.05/p < 0.05). TT level was significantly
      decreased in patients with >= 4 episodes of nocturia. The TT level was
      significantly related to the presence of severe LUTS (p < 0.05). CONCLUSIONS:
      Endogenous testosterone may have a beneficial effect on lower urinary tract
      function and that a high frequency of nocturia may induce testosterone
      deficiency.

PMID- 22385129
TI  - Low castes have poor access to visceral leishmaniasis treatment in Bihar, India.
AB  - OBJECTIVES: Bihar, the poorest state in India, concentrates most of the visceral
      leishmaniasis (VL) cases in the country. A large proportion of the poor rural
      communities where VL is endemic are marginalized by their socio-economic status,
      intrinsically related to the caste system. In this study, we evaluated whether
      people from low socio-economic strata had difficulties accessing VL treatment in
      Bihar. As a secondary outcome, we evaluated whether people delaying their VL
      treatment had poorer clinical indicators at admission. METHODS: Data on 2187
      patients with VL treated by Medecins Sans Frontieres (MSF) in Vaishali district
      from July 2007 to December 2008 were analysed. Patients who reported having onset
      of symptoms >=8 weeks before admission were defined as 'late presenters'.
      Logistic regression models were used to evaluate whether low castes had higher
      risk to be 'late presenters' compared to the rest of castes and whether 'late
      presenters' had poorer indicators at admission (i.e. haemoglobin level, spleen
      size). RESULTS: After adjusting for age, gender and distance to VL treatment
      facility, Mushars (the lowest caste in Bihar) had twice the odds to be 'late
      presenters' compared to the rest of castes (OR 2.05, 95% CI: 1.24-2.38). Subjects
      that had VL symptoms for >=8 weeks had a larger spleen and lower haemoglobin
      level than those that were treated earlier. CONCLUSION: Low castes have poor
      access to VL treatment in Bihar, and late presenters have poorer clinical
      indicators at admission. These findings have implications at individual and
      community levels and should stimulate targeted VL control programmes to ensure
      that marginalized communities in Bihar are properly treated.

PMID- 22385130
TI  - Constructing and responding to low-risk drinking guidelines: conceptualisation,
      evidence and reception.

PMID- 22385132
TI  - Low voltage, hysteresis free, and high mobility transistors from all-inorganic
      colloidal nanocrystals.
AB  - High-mobility solution-processed all-inorganic solid state nanocrystal (NC)
      transistors with low operation voltage and near-zero hysteresis are demonstrated
      using high-capacitance ZrO(x) and hydroxyl-free Cytop gate dielectric materials.
      The use of inorganic capping ligands (In(2)Se(4)(2-) and S(2-)) allowed us to
      achieve high electron mobility in the arrays of solution-processed CdSe
      nanocrystals. We also studied the hysteresis behavior and switching speed of NC
      based field effect devices. Collectively, these analyses helped to understand the
      charge transport and trapping mechanisms in all-inorganic NCs arrays. Finally, we
      have examined the rapid thermal annealing as an approach toward high-performance
      solution-processed NCs-based devices and demonstrated transistor operation with
      mobility above 30 cm(2)/(V s) without compromising low operation voltage and
      hysteresis.

PMID- 22385131
TI  - Vitamin d deficiency in postmenopausal breast cancer survivors.
AB  - PURPOSE: Breast cancer survivors (BCS) taking aromatase inhibitors (AIs) are at
      an increased risk for decreased bone density and fractures. Given the role
      vitamin D plays in bone metabolism, we examined the prevalence of and risk
      factors for vitamin D deficiency in a study of postmenopausal BCS on AIs.
      METHODS: We collected data on 391 postmenopausal women with stage I-III breast
      cancer on AI therapy. Vitamin D levels were measured by radioimmunoassay from
      patients' sera; deficiency was defined as a level < 30 ng/mL. Multivariate models
      were created to assess risk factors for deficiency. RESULTS: The median vitamin D
      level was 35 ng/mL (range 6.78-93.15), and 35% of women were vitamin D deficient.
      When adjusting for age and vitamin D supplementation, minority participants were
      more likely to be vitamin D deficient than white women, (adjusted odds ratio
      [AOR] 2.18, 95% confidence interval [CI]1.22-3.89, p=0.009). Both overweight (AOR
      3.05, 95% CI 1.72-5.41, p<0.001) and obese participants (AOR 3.21, 95% CI 1.79
      5.78, p<0.001) had higher deficiency rates than did normal weight participants.
      CONCLUSIONS: Hypovitaminosis D is common in BCS, and those who are nonwhite or
      overweight are at a higher risk of deficiency despite taking vitamin D
      supplements.

PMID- 22385133
TI  - Effects of a meal rich in 1,3-diacylglycerol on postprandial cardiovascular risk
      factors and the glucose-dependent insulinotropic polypeptide in subjects with
      high fasting triacylglycerol concentrations.
AB  - It was previously reported that compared to triacylglycerol (TAG) oil,
      diacylglycerol (DAG) oil improves postprandial lipid response. However, the
      effects of DAG oil on postprandial hyperglycemia and incretin response have not
      yet been determined. In this study, the effects of DAG oil on both postprandial
      hyperlipidemia and hyperglycemia and the response to the glucose-dependent
      insulinotropic polypeptide (GIP) were studied. This randomized, double-blind,
      crossover study analyzed data for 41 individuals with high fasting
      triacylglycerol concentrations. The subjects ingested test meals (30.3 g of
      protein, 18.6 g of fat, and 50.1 g of carbohydrate) containing 10 g of DAG oil
      (DAG meal) or TAG oil (TAG meal) after fasting for at least 12 h. Blood samples
      were collected prior to and 0.5, 2, 3, 4, and 6 h after ingestion of the test
      meal. Postprandial TAG concentrations were significantly lower after the DAG meal
      compared with the TAG meal. Postprandial TAG, insulin, and GIP concentrations
      were significantly lower after the DAG meal compared with the TAG meal in 26
      subjects with fasting serum TAG levels between 1.36 and 2.83 mmol/L. DAG-oil
      based meals, as a replacement for TAG oil, may provide cardiovascular benefits in
      high-risk individuals by limiting lipid and insulin excursions.

PMID- 22385134
TI  - Borg: an auto-adaptive many-objective evolutionary computing framework.
AB  - This study introduces the Borg multi-objective evolutionary algorithm (MOEA) for
      many-objective, multimodal optimization. The Borg MOEA combines epsilon
      dominance, a measure of convergence speed named epsilon-progress, randomized
      restarts, and auto-adaptive multioperator recombination into a unified
      optimization framework. A comparative study on 33 instances of 18 test problems
      from the DTLZ, WFG, and CEC 2009 test suites demonstrates Borg meets or exceeds
      six state of the art MOEAs on the majority of the tested problems. The
      performance for each test problem is evaluated using a 1,000 point Latin
      hypercube sampling of each algorithm's feasible parameterization space. The
      statistical performance of every sampled MOEA parameterization is evaluated using
      50 replicate random seed trials. The Borg MOEA is not a single algorithm; instead
      it represents a class of algorithms whose operators are adaptively selected based
      on the problem. The adaptive discovery of key operators is of particular
      importance for benchmarking how variation operators enhance search for complex
      many-objective problems.

PMID- 22385135
TI  - The effect of ursodeoxycholic acid on oxidative stress level and DNase activity
      in rat liver after bile duct ligation.
AB  - Accumulation of hydrophobic bile acids (BAs) during cholestasis plays an
      important role in apoptosis initiation as well as oxidative stress increase in
      liver cells. Ursodeoxycholic acid (UDCA) acts as a protector in BA-induced cell
      injury.The aim of the study was to evaluate the effect of UDCA on oxidative
      stress level and DNase I and II activity caused by liver injury in bile duct
      ligation (BDL) rats.Wistar rats were divided in four groups: group 1, control
      (sham-operated); group 2, sham-operated and injected with UDCA (30 mg/kg); group
      3,animals with BDL; and group 4,UDCA-treatedcholestatic rats. Animals were
      sacrificed after 9 days. Malondialdehyde (MDA; lipid peroxidation end-product)
      level and protein-molecule oxidative modification (carbonyl group content)
      significantly increased in BDL rat liver. Catalase (CAT) activity in liver tissue
      was found to be decreased in BDL rats. In addition, xanthine oxidase (XO)
      activity, which is thought to be one of the key enzymes producing reactive oxygen
      species, was found to be increased in the cholestatic group. The apoptotic effect
      in cholestasis was probably triggered by the increased activation of DNase I and
      II. The protective effect of UDCA on liver tissue damage in BDL rats, in
      comparison to cholestatic liver, were 1) decrease of MDA levels, 2) increased CAT
      activity, 3) reduced XO activity, and 4) effect on terminal apoptotic reaction,
      shown as a decrease in DNase I and II activity.Therefore, UDCA may be useful in
      the preservation of liver function in cholestasis treatment.

PMID- 22385136
TI  - Impact of the FTO gene variation on fat oxidation and its potential influence on
      body weight in women with polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder where
      insulin resistance might be involved in the development of endocrine and
      metabolic abnormalities. It has recently been shown that the FTO gene modifies
      weight, fat mass and insulin sensitivity in women with PCOS, where its role might
      be larger than in other phenotypes. OBJECTIVE: The aim of this study was to
      estimate the effect of a variation of the FTO gene on carbohydrate and lipid
      oxidation in PCOS women. PATIENTS: The study group consisted of 65 women with
      PCOS and 28 healthy, normally menstruating women. MEASUREMENTS: Clinical
      examination, anthropometric measurements, euglycaemic hyperinsulinaemic clamp and
      measurements of serum sex hormones were performed. Carbohydrate and lipid
      oxidation were evaluated with indirect calorimetry in the baseline state and
      during last 30 min of the clamp. The FTO rs9939609 polymorphism was genotyped
      using the restriction fragment length polymorphism method. RESULTS: There were no
      differences in carbohydrate and lipid oxidation between PCOS and control women.
      In the PCOS group, TT homozygotes had higher baseline fat oxidation in comparison
      with carriers of the A allele (P = 0.018), which was not found in the control
      group. We did not observe the effect of the FTO gene variation on insulin
      stimulated lipid oxidation and neither on the baseline nor on the insulin
      stimulated carbohydrate oxidation. CONCLUSION: Our data show that this FTO gene
      variation might influence the baseline lipid oxidation in PCOS patients. This
      might potentially be one of the mechanisms explaining the impact of the FTO gene
      on body weight in PCOS.

PMID- 22385137
TI  - Synthesis and anti-HIV activities of suramin conjugates of 3'-fluoro- 2',3'
      dideoxythymidine and 3'-azido-2',3'-dideoxythymidine.
AB  - Conjugates between suramin, a polyanionic naphthalene sulfonate derivative, and
      nucleoside reverse transcriptase inhibitors (NRTIs), 3'-azido-2',3'
      dideoxythymidine (AZT) and 3'-fluoro-2',3'-dideoxythymidine (FLT), were designed
      to create an antiretroviral with multiple mechanisms of action that could be
      developed as an anti-HIV topical microbicide candidate. The anti-HIV activity of
      these conjugates was compared with that of suramin and the corresponding physical
      mixtures of suramin and nucleosides. The conjugates were synthesized as sulfonate
      esters by reaction of suramin with the nucleoside analogs in the presence of
      phosphorus pentoxide, and were tested against X4 and R5 labadapted strains of HIV
      1. Suramin conjugates of AZT (EC50= 19.4 MUg/ml) and FLT (EC50= 23.6 MUg/ml)
      demonstrated improved anti-HIV activity against X4 strain of virus by 2.5 and 2
      fold, respectively, when compared with suramin. The physical mixtures of suramin
      with nucleosides significantly improved anti-HIV activity of suramin against X4
      strain by more than 55 fold.

PMID- 22385138
TI  - Laterality of basic auditory perception.
AB  - Laterality (left-right ear differences) of auditory processing was assessed using
      basic auditory skills: (1) gap detection, (2) frequency discrimination, and (3)
      intensity discrimination. Stimuli included tones (500, 1000, and 4000 Hz) and
      wide-band noise presented monaurally to each ear of typical adult listeners. The
      hypothesis tested was that processing of tonal stimuli would be enhanced by left
      ear (LE) stimulation and noise by right ear (RE) presentations. To investigate
      the limits of laterality by (1) spectral width, a narrow-band noise (NBN) of 450
      Hz bandwidth was evaluated using intensity discrimination, and (2) stimulus
      duration, 200, 500, and 1000 ms duration tones were evaluated using frequency
      discrimination. A left ear advantage (LEA) was demonstrated with tonal stimuli in
      all experiments, but an expected REA for noise stimuli was not found. The NBN
      stimulus demonstrated no LEA and was characterised as a noise. No change in
      laterality was found with changes in stimulus durations. The LEA for tonal
      stimuli is felt to be due to more direct connections between the left ear and the
      right auditory cortex, which has been shown to be primary for spectral analysis
      and tonal processing. The lack of a REA for noise stimuli is unexplained. Sex
      differences in laterality for noise stimuli were noted but were not statistically
      significant. This study did establish a subtle but clear pattern of LEA for
      processing of tonal stimuli.

PMID- 22385139
TI  - Lateral preference and schizotypy revisited: comparison of handedness measurement
      and classification methods.
AB  - A sample of 256 undergraduate students was administered five schizotypy scales
      and a lateral preference questionnaire consisting of 41 handedness items, in
      order to examine the effect of different approaches to the measurement and
      classification of handedness on the relationship between schizotypy and lateral
      preference. The extended handedness questionnaire included the 12 items of
      Annett's handedness questionnaire, the 10 items of Oldfield's (1971) Edinburgh
      Handedness Inventory, the 19 items of the lateral preference questionnaire used
      by Kelley and Coursey (1992a), and additional items from Steenhuis and Bryden's
      (1989) 32-item Waterloo Handedness Inventory, allowing the examination and
      comparison of a variety of handedness classification schemes and the computation
      of several continuous measures of handedness, and comparison of their
      relationships to schizotypy. Different approaches to the measurement and
      classification of handedness yielded somewhat different findings concerning the
      relationship to schizotypy, which also varied depending on gender and the
      schizotypy measure involved. Among males, higher schizotypy scores were
      associated with more dextral lateral preference, whereas among females higher
      schizotypy was associated with mixed right-handedness.

PMID- 22385140
TI  - Hand clasping, arm folding, and handedness: relationships and strengths of
      preference.
AB  - We investigated via a survey the relationship between hand clasping, arm folding,
      and handedness. We aimed to provide new data on degree of preference for each of
      these lateralities. We also examined the relative importance of thumb position
      versus interdigitisation of the fingers in determining one's comfort in a hand
      clasping position. We explored this in the context of the fact that sensory
      acuity is greater for the thumb than other fingers, suggesting that preference
      for how the fingers are intermeshed may be more influenced by thumb than finger
      position. Lastly we performed an exploratory analysis to determine if self
      reported menstrual phase-known to influence turning bias-also influences hand
      clasping, arm folding or the strength of one's handedness. Our study suggests
      that lateral preferences for hand clasping, arm folding, and handedness are
      independent. However, the degrees of lateral preference for hand clasping and arm
      folding are correlated. Our exploration of the relative importance of thumbs
      versus fingers to hand clasping revealed some trends that were not statistically
      significant, but worth future exploration. Our data on menstrual phase showed a
      reduced strength of preference for arm folding in mid-luteal females versus non
      mid-luteal females.

PMID- 22385141
TI  - Touching base: The effect of participant and stimulus modulation factors on a
      haptic line bisection task.
AB  - Acquiring information about our environment through touch is vital in everyday
      life. Yet very little literature exists about factors that may influence haptic
      or tactile processing. Recent neuroimaging studies have reported haptic
      laterality effects that parallel those reported in the visual literature. With
      the use of a haptic variant of the classical line bisection task, the present
      study aimed to determine the presence of laterality effects on a behavioural
      level. Specifically, three handedness groups including strong dextrals, strong
      sinistrals, and-the to-date largely neglected group of-mixed-handers were
      examined in their ability to accurately bisect stimuli constructed from
      corrugated board strips of various lengths. Stimulus factors known to play a role
      in visuospatial perception including stimulus location, the hand used for
      bisection, and direction of exploration were systematically varied through pseudo
      randomisation. Similar to the visual domain, stimulus location and length as well
      as participants' handedness and the hand used for bisection exerted a significant
      influence on participants' estimate of the centre of haptically explored stimuli.
      However, these effects differed qualitatively from those described for the visual
      domain, and the factor direction of exploration did not exert any significant
      effect. This indicates that laterality effects reported on a neural level are
      sufficiently pronounced to result in measurable behavioural effects. The results,
      first, add to laterality effects reported for the visual and auditory domain,
      second, are in line with supramodal spatial processing and third, provide
      additional evidence to a conceptualisation of pseudoneglect and neglect as signs
      of hemispheric attentional asymmetries.

PMID- 22385142
TI  - Sex and hemispheric differences in facial invariants extraction.
AB  - This present study investigates sex differences in hemispheric cooperation during
      a facial identity matching task. The method used was a divided visual field
      paradigm in which the probe face was neutral or expressive and the target face
      was always neutral. Probe and target faces were presented both unilaterally and
      sequentially. A total of 28 right-handed women and 32 right-handed men
      participated in this study. The results confirm the women's advantage in face
      recognition and reveal symmetrical interhemispheric cooperation in women only. In
      men, processing time was faster when the probe face appeared in the left visual
      field-and encoded by the right hemisphere-and the target in the right visual
      field-projected to the left hemisphere-compared to the reverse direction.
      Interestingly, the data also show that women were not influenced by the
      expression of the probe face when matching identity, whereas men were always
      faster when the probe face was neutral, like the target, than when it was
      expressive. These results are discussed in light of Bruce and Young's (1986)
      model, and in terms of view-dependent and view-independent processes.

PMID- 22385143
TI  - Familial sinistrality and handedness in patients with first episode
      schizophrenia: the EUFEST study.
AB  - The population with schizophrenia is characterised by a leftward shift in
      handedness-sinistrality. However, findings are inconsistent in chronic patients,
      and familial sinistrality (FS), defined as the presence of left-handed close
      relatives, might contribute to the discrepancies. Therefore the aim of this study
      was to investigate the strength of manual lateralisation in patients with first
      episode schizophrenia, taking into account familial sinistrality. The Edinburgh
      Inventory (EI) allowed us to categorise 179 patients from the EUFEST study and
      189 controls presenting "strong handedness" (SH: EI absolute value between ?81?
      and ?100?) or "weak-handedness" (WH: EI value between -80 and +80). The nominal
      logistic regression did not show an FS effect, but a nearly significant
      interaction between illness and FS (p =.07). There were fewer participants
      without FS presenting SH among patients (99/151: 65.6%) than among controls
      (134/164: 81.7%, p =.001). In contrast, the number of participants with FS
      presenting SH was similar between controls (68%) and patients (75%, p =.57). The
      presence of left-handed relatives (FS + ) tended to reduce manual lateralisation,
      but only in controls. This supports the notion that reduced manual lateralisation
      in schizophrenia is related to the illness rather than to familial left
      handedness.

PMID- 22385146
TI  - Addendum to: Coagulase-negative Staphylococcus bacteraemia accounts for one third
      of Staphylococcus bacteraemia in a French university hospital.

PMID- 22385144
TI  - Individual differences in reading skill and language lateralisation: a cluster
      analysis.
AB  - Individual differences in reading and cerebral lateralisation were investigated
      in 200 college students who completed reading assessments and divided visual
      field word recognition tasks, and received a structural MRI scan. Prior studies
      on this data set indicated that little variance in brain-behaviour correlations
      could be attributed to the effects of sex and handedness variables (Chiarello,
      Welcome, Halderman, & Leonard, 2009; Chiarello, Welcome, Halderman, Towler, et
      al., 2009; Welcome et al., 2009). Here a more bottom-up approach to behavioural
      classification (cluster analysis) was used to explore individual differences that
      need not depend on a priori decisions about relevant subgroups. The cluster
      solution identified four subgroups of college age readers with differing reading
      skill and visual field lateralisation profiles. These findings generalised to
      measures that were not included in the cluster analysis. Poorer reading skill was
      associated with somewhat reduced VF asymmetry, while average readers demonstrated
      exaggerated RVF/left hemisphere advantages. Skilled readers had either reduced
      asymmetries, or asymmetries that varied by task. The clusters did not differ by
      sex or handedness, suggesting that there are identifiable sources of variance
      among individuals that are not captured by these standard participant variables.
      All clusters had typical leftward asymmetry of the planum temporale. However, the
      size of areas in the posterior corpus callosum distinguished the two subgroups
      with high reading skill. A total of 17 participants, identified as multivariate
      outliers, had unusual behavioural profiles and differed from the remainder of the
      sample in not having significant leftward asymmetry of the planum temporale. A
      less buffered type of neurodevelopment that is more open to the effects of random
      genetic and environmental influences may characterise such individuals.

PMID- 22385147
TI  - White sponge nevus treated with chlorhexidine.

PMID- 22385148
TI  - Chemical genetics and its potential in cardiac stem cell therapy.
AB  - Over the last decade or so, intensive research in cardiac stem cell biology has
      led to significant discoveries towards a potential therapy for cardiovascular
      disease; the main cause of morbidity and mortality in humans. The major goal
      within the field of cardiovascular regenerative medicine is to replace lost or
      damaged cardiac muscle and coronaries following ischaemic disease. At present, de
      novo cardiomyocytes can be generated either in vitro, for cell transplantation or
      disease modelling using directed differentiation of embryonic stem cells or
      induced pluripotent stem cells, or in vivo via direct reprogramming of resident
      adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or
      progenitor cells. A major bottleneck with all of these approaches is the low
      efficiency of cardiomyocyte differentiation alongside their relative functional
      immaturity. Chemical genetics, and the application of phenotypic screening with
      small molecule libraries, represent a means to enhance understanding of the
      molecular pathways controlling cardiovascular cell differentiation and, moreover,
      offer the potential for discovery of new drugs to invoke heart repair and
      regeneration. Here, we review the potential of chemical genetics in cardiac stem
      cell therapy, highlighting not only the major contributions to the field so far,
      but also the future challenges.

PMID- 22385149
TI  - Home injuries in Italy: patterns of injury and the most exposed people.
AB  - Home injuries are a significant public health problem in developed and developing
      countries. To support future policies for reducing their occurrence and
      controlling their consequences, this study investigated the home injuries
      situation in Italy in 1999, using a nation-representative sample. The weighted
      correspondence analysis showed four different patterns of injury and seven
      profiles of the people most exposed to them. As results of this study falls were
      followed by bumps and cuts requiring specialist assistance then burns. Women were
      the most exposed to burn and fall risks and men to the risk of cuts and bumps.
      Among the elderly and children, falls and bumps leading to fractures, wounds or
      other consequences were frequent. The risks were highest for people with a lower
      level of education. Bumps and cuts were prevalent among unmarried and with the
      highest education level subjects. These injury risks were higher for young males.
      Cuts in adults doing do-it-yourself jobs had the worst consequences, while
      domestic work cuts generally did not need medical treatment. Burns occurred
      almost exclusively in the kitchen (90%) and did not need specialist assistance.
      Because home injuries are largely preventable, an efficient public health policy
      could promote and disseminate home safety culture.

PMID- 22385150
TI  - In situ TEM investigation of congruent phase transition and structural evolution
      of nanostructured silicon/carbon anode for lithium ion batteries.
AB  - It is well-known that upon lithiation, both crystalline and amorphous Si
      transform to an armorphous Li(x)Si phase, which subsequently crystallizes to a
      (Li, Si) crystalline compound, either Li(15)Si(4) or Li(22)Si(5). Presently, the
      detailed atomistic mechanism of this phase transformation and the degradation
      process in nanostructured Si are not fully understood. Here, we report the phase
      transformation characteristic and microstructural evolution of a specially
      designed amorphous silicon (a-Si) coated carbon nanofiber (CNF) composite during
      the charge/discharge process using in situ transmission electron microscopy and
      density function theory molecular dynamic calculation. We found the
      crystallization of Li(15)Si(4) from amorphous Li(x)Si is a spontaneous, congruent
      phase transition process without phase separation or large-scale atomic motion,
      which is drastically different from what is expected from a classic nucleation
      and growth process. The a-Si layer is strongly bonded to the CNF and no
      spallation or cracking is observed during the early stages of cyclic
      charge/discharge. Reversible volume expansion/contraction upon charge/discharge
      is fully accommodated along the radial direction. However, with progressive
      cycling, damage in the form of surface roughness was gradually accumulated on the
      coating layer, which is believed to be the mechanism for the eventual capacity
      fade of the composite anode during long-term charge/discharge cycling.

PMID- 22385151
TI  - Comment on vitamins D and E supplementation.

PMID- 22385152
TI  - Water use for Shale-gas production in Texas, U.S.
AB  - Shale-gas production using hydraulic fracturing of mostly horizontal wells has
      led to considerable controversy over water-resource and environmental impacts.
      The study objective was to quantify net water use for shale-gas production using
      data from Texas, which is the dominant producer of shale gas in the U.S. with a
      focus on three major plays: the Barnett Shale (~15,000 wells, mid-2011), Texas
      Haynesville Shale (390 wells), and Eagle Ford Shale (1040 wells). Past water use
      was estimated from well-completion data, and future water use was extrapolated
      from past water use constrained by shale-gas resources. Cumulative water use in
      the Barnett totaled 145 Mm(3) (2000-mid-2011). Annual water use represents ~9% of
      water use in Dallas (population 1.3 million). Water use in younger (2008-mid
      2011) plays, although less (6.5 Mm(3) Texas-Haynesville, 18 Mm(3) Eagle Ford), is
      increasing rapidly. Water use for shale gas is <1% of statewide water
      withdrawals; however, local impacts vary with water availability and competing
      demands. Projections of cumulative net water use during the next 50 years in all
      shale plays total ~4350 Mm(3), peaking at 145 Mm(3) in the mid-2020s and
      decreasing to 23 Mm(3) in 2060. Current freshwater use may shift to brackish
      water to reduce competition with other users.

PMID- 22385153
TI  - Prevalence and associated psychosocial factors of increased hand hygiene practice
      during the influenza A/H1N1 pandemic: findings and prevention implications from a
      national survey in Taiwan.
AB  - OBJECTIVE: To investigate increased hand hygiene practice in response to the
      pandemic influenza A/H1N1 (pH1N1) and its associated psychosocial factors in the
      Taiwanese general population. METHODS: A national telephone survey using random
      digit dialing was conducted on October 28-30, 2009 in Taiwan, resulting in a
      final sample of 1079 participants aged 15 or older. RESULTS: Seventy-seven per
      cent reported that they increased hand hygiene practice during the pH1N1
      epidemic. Multivariate logistic regression analysis showed that increased hand
      hygiene practice was associated with health beliefs that pH1N1 was more
      transmissible than avian influenza (OR = 1.42); that pH1N1 was slightly more
      severe in Taiwan compared with other countries (OR = 1.59); that handwashing was
      very effective in preventing pH1N1 (OR = 3.12), and that handwashing after
      contact with possibly pH1N1-contaminated objects/surfaces was not very difficult
      (OR = 2.14) or not difficult at all (OR = 2.49). CONCLUSIONS: These findings
      suggest that future campaigns to promote preventive health behaviour in the
      public should consider communicating evidence-based information concerning the
      effectiveness of the recommended preventive behaviour, comparing the emerging
      epidemic with prior local outbreaks, and not overplaying the seriousness of the
      disease with fear tactics.

PMID- 22385154
TI  - Variation in surgical site infection monitoring and reporting by state.
AB  - OBJECTIVE: Surgical site infections (SSIs) are common, costly, and often
      preventable. There are no national requirements for measuring or reporting
      hospital SSI rates and state-level monitoring occurs with little coordination
      between states. We designed a study to describe the current status of SSI
      reporting in the United States. METHODS: We reviewed SSI monitoring and reporting
      legislation in all 50 states in September 2010. Data collected included whether
      SSI monitoring and reporting legislation exists, if public reporting is required,
      how the data are accessible, and for which procedures SSI data are reported.
      RESULTS: Twenty-one (42%) states have legislation for SSI monitoring and
      reporting. All 21 of these states require public release of findings. Of the
      states with legislation, eight (38%) currently have SSI data available publicly.
      A range of two to seven procedures were reported for SSI measurement by
      individual states. Eighteen (86%) states use state agency websites to make their
      data publicly available. CONCLUSION: There is wide variation in state monitoring
      and reporting of SSI rates. Standardized reporting may be needed so that
      consumers can make informed health choices based on quality metrics.

PMID- 22385155
TI  - Pregnancy after percutaneous epididymal sperm aspiration in an 81-year-old man
      with obstructive azoospermia.
AB  - There has been observed a trend to delay childbearing, reflecting couple's desire
      to have children at older ages. Maternal age is a well-known factor that
      influences the achievement of a pregnancy. In contrast, there are few studies
      examining the effect of paternal age on the outcomes of assisted reproductive
      technologies (ART), and results are conflicting. Our patient was vasectomised at
      the age of 60 years, and his wife was 38 years old. A total of four metaphase II
      oocytes were inseminated 4 h later (day 0) by intracytoplasmic sperm injection
      using spermatozoa from percutaneous epididymal sperm aspiration. On day 2, the
      three resulting embryos were transferred (two had four cells, and one had two
      cells). Two healthy infants were born at the 37th gestational week by caesarean
      section. Although the effect of paternal age on ART outcomes and results are
      conflicting, this case report contributes to point out that advanced age of the
      man has probably lesser negative influence in the reproductive function.

PMID- 22385156
TI  - Physiological ecology of desert biocrust moss following 10 years exposure to
      elevated CO2: evidence for enhanced photosynthetic thermotolerance.
AB  - In arid regions, biomes particularly responsive to climate change, mosses play an
      important biogeochemical role as key components of biocrusts. Using the biocrust
      moss Syntrichia caninervis collected from the Nevada Desert Free Air CO2
      Enrichment Facility, we examined the physiological effects of 10 years of
      exposure to elevated CO2, and the effect of high temperature events on the
      photosynthetic performance of moss grown in CO2-enriched air. Moss exposed to
      elevated CO2 exhibited a 46% decrease in chlorophyll, a 20% increase in carbon
      and no difference in either nitrogen content or photosynthetic performance.
      However, when subjected to high temperatures (35-40 degrees C), mosses from the
      elevated CO2 environment showed higher photosynthetic performance and photosystem
      II (PSII) efficiency compared to those grown in ambient conditions, potentially
      reflective of a shift in nitrogen allocation to components that offer a higher
      resistance of PSII to heat stress. This result suggests that mosses may respond
      to climate change in markedly different ways than vascular plants, and observed
      CO2-induced photosynthetic thermotolerance in S. caninervis will likely have
      consequences for future desert biogeochemistry.

PMID- 22385157
TI  - The perceived health risks of cannabis use in an Australian household survey.
AB  - INTRODUCTION AND AIMS: Perceived risks of cannabis use have rarely been
      researched in Australia. This paper reports on the beliefs about the adverse
      effects of cannabis use on health, social well-being, driving, mental health and
      changes in cannabis over time. DESIGN AND METHODS: Survey of 918 Australian
      adults was conducted as part of a quarterly omnibus self-report survey of an
      established panel. RESULTS: Respondents believed that cannabis use can cause
      health and social problems, can adversely affect a person's ability to drive a
      car, can be addictive, and can lead to use of other illicit drugs. They were
      uncertain as to whether cannabis can cause schizophrenia and depression, and
      whether cannabis had become more potent over time. IMPLICATIONS: Prevention
      efforts should focus on educating the Australian people about the nature of
      cannabis-related harms.

PMID- 22385158
TI  - Long-term consumption of aspartame and brain antioxidant defense status.
AB  - The present study investigated the effect of long-term intake of aspartame, a
      widely used artificial sweetener, on antioxidant defense status in the rat brain.
      Male Wistar rats weighing 150-175 g were randomly divided into three groups as
      follows: The first group was given aspartame at a dose of 500 mg/kg body weight
      (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w.,
      respectively, in a total volume of 3 mL of water; and the control rats received 3
      mL of distilled water. Oral intubations were done in the morning, daily for 180
      days. The concentration of reduced glutathione (GSH) and the activity of
      glutathione reductase (GR) were significantly reduced in the brain of rats that
      had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a
      significant reduction in GSH concentration was observed in the 500-mg/kg b.w.
      aspartame-treated group. Histopathological examination revealed mild vascular
      congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results
      of this experiment indicate that long-term consumption of aspartame leads to an
      imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the
      mechanism involving the glutathione-dependent system.

PMID- 22385160
TI  - High-yield transfer printing of metal-insulator-metal nanodiodes.
AB  - Nanoscale metal-insulator-metal (MIM) diodes represent important devices in the
      fields of electronic circuits, detectors, communication, and energy, as their
      cutoff frequencies may extend into the "gap" between the electronic microwave
      range and the optical long-wave infrared regime. In this paper, we present a
      nanotransfer printing method, which allows the efficient and simultaneous
      fabrication of large-scale arrays of MIM nanodiode stacks, thus offering the
      possibility of low-cost mass production. In previous work, we have demonstrated
      the successful transfer and electrical characterization of macroscopic
      structures. Here, we demonstrate for the first time the fabrication of several
      millions of nanoscale diodes with a single transfer-printing step using a
      temperature-enhanced process. The electrical characterization of individual MIM
      nanodiodes was performed using a conductive atomic force microscope (AFM) setup.
      Our analysis shows that the tunneling current is the dominant conduction
      mechanism, and the electrical measurement data agree well with experimental data
      on previously fabricated microscale diodes and numerical simulations.

PMID- 22385159
TI  - Structural basis for calcium and phosphatidylserine regulation of phospholipase C
      delta1.
AB  - Many membrane-associated enzymes, including those of the phospholipase C (PLC)
      superfamily, are regulated by specific interactions with lipids. Previously, we
      have shown that the C2 domain of PLC delta1 is required for phosphatidylserine
      (PS)-dependent enzyme activation and that activation requires the presence of
      Ca(2+). To identify the site of interaction and the role of Ca(2+) in the
      activation mechanism, we mutagenized three highly conserved Ca(2+) binding
      residues (Asp-653, Asp-706, and Asp-708) to Gly in the C2 domain of PLC delta1.
      The PS-dependent Ca(2+) binding affinities of the mutant enzymes D653G, D706G,
      and D708G were reduced by 1 order of magnitude, and the maximal level of Ca(2+)
      binding was reduced to half of that of the native enzyme. The level of Ca(2+)
      dependent PS binding was also reduced in the mutant enzymes. Under basal
      conditions, the Ca(2+) dependence and the maximal level of hydrolysis of
      phosphatidylinositol 4,5-bisphosphate were not altered in the mutants. However,
      the Ca(2+)-dependent PS stimulation was severely defective. PS reduces the K(m)
      of the native enzyme almost 20-fold, but far less for the mutants. Replacing Asp
      653, Asp-706, and Asp-708 simultaneously with glycine in the C2 domain of PLC
      delta1 leads to a complete and selective loss of the stimulation and binding by
      PS. These results show that D653, D706, and D708 are required for Ca(2+) binding
      in the C2 domain and demonstrate a mechanism by which C2 domains can mediate
      regulation of enzyme activity by specific lipid ligands.

PMID- 22385161
TI  - Screening, identification, and potential interaction of active compounds from
      Eucommia ulmodies leaves binding with bovine serum albumin.
AB  - The aqueous extract of  Eucommia ulmoides  leaves has been commonly known as Du
      zhong tea as a functional health food for the treatment of hypertension,
      hypercholesterolemia, and fatty liver. This study developed a centrifugal
      ultrafiltration-high-performance liquid chromatography (HPLC) method for
      screening and identification of bioactive compounds in  E. ulmoides  leaves
      binding with bovine serum albumin (BSA). Six active compounds were screened,
      isolated, and elucidated by their ultraviolet (UV), electrospray ionization-mass
      spectrometry (ESI-MS), and nuclear magnetic resonance (NMR) data as geniposidic
      acid (1), caffeic acid (2), chlorogenic acid (3), quercetin-3-O-sambubioside (4),
      rutin (5), and isoquercitrin (6). The interaction between active compounds and
      BSA was investigated in the absence and presence of other compounds by quenching
      the intrinsic BSA fluorescence. The results indicated that the structures
      significantly affected the binding process. The values of binding constants for
      compounds 2-6 were in the range of 10(5)-10(6) mol L(-1), while geniposidic acid
      (1) hardly quenching the BSA intrinsic fluorescence. However, the quenching
      process of geniposidic acid was easily affected in the presence of other active
      compounds. The formation of the geniposidic acid-phenylpropanoid (flavonoid)
      complex could increase the binding affinity of geniposidic acid with BSA;
      however, the increased steric hindrance of the complex may make phenylpropanoid
      or flavonoid dissociate from BSA and then decrease their affinities.

PMID- 22385163
TI  - Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology.
AB  - The lactic acid bacteria (LAB) are essential for food fermentations and their
      impact on gut physiology and health is under active exploration. In addition to
      their well-studied fermentation metabolism, many species belonging to this
      heterogeneous group are genetically equipped for respiration metabolism. In LAB,
      respiration is activated by exogenous heme, and for some species, heme and
      menaquinone. Respiration metabolism increases growth yield and improves fitness.
      In this review, we aim to present the basics of respiration metabolism in LAB,
      its genetic requirements, and the dramatic physiological changes it engenders. We
      address the question of how LAB acquired the genetic equipment for respiration.
      We present at length how respiration can be used advantageously in an industrial
      setting, both in the context of food-related technologies and in novel potential
      applications.

PMID- 22385162
TI  - Predictors of atrio-ventricular conduction disease, long-term outcomes in
      patients with myotonic dystrophy types I and II.
AB  - BACKGROUND: Patients with myotonic dystrophy (DM) have an annual mortality of
      approximately 3.5%, one-third of which is sudden cardiac death. The predictors of
      cardiac conduction disease in these patients are incompletely defined. METHODS: A
      single-center cohort study included 211 patients with DM type 1 (DM1) and 25 DM
      type 2 (DM2). A severe electrocardiogram (ECG) abnormality was defined as a PR
      interval of >=240 ms or QRS duration of >=120 ms. RESULTS: A severe ECG
      abnormality was found in 24% of DM1 patients and 17% of DM2 patients. Among DM1
      patients, those with a severe ECG abnormality were older (41.6 +/- 14.6 vs 35.4
      +/- 12.6 years) and more likely to have hypertension (13.2% vs 4.2%, P = 0.038),
      heart failure (4.4% vs 0%, P = 0.056), atrial arrhythmias (6.6% vs 0.7%, P <
      0.001), a higher number of trinucleotide repeats (689 +/- 451 vs 474 +/- 322, P =
      0.01), and a family history of sudden cardiac death (26.7% vs 5.6%, P < 0.001) or
      pacemaker implantation (20% vs 0.7%, P < 0.001). Pacemakers or defibrillators
      were implanted in 14% of all patients, including 65% of patients with severe ECG
      abnormalities. During 57 +/- 46 months, 13 patients died (1.16% per year),
      including three patients who died suddenly, two of whom had normally functioning
      pacemakers. CONCLUSION: In DM1, atrio-ventricular conduction disease is
      associated with increasing age, concomitant cardiovascular disease, nucleotide
      repeat length, and family history. The systematic identification of conduction
      disease and aggressive use of prophylactic pacemakers is associated with low rate
      of sudden cardiac death.

PMID- 22385164
TI  - Alternatives to those artificial FD&C food colorants.
AB  - Replacement of artificial food dyes with natural colorants is a current marketing
      trend, notwithstanding the fact that neither the United States nor the European
      Union (EU) has defined natural with respect to food colors. Consumer groups have
      concerns over the safety of synthetic colorants, and in addition, many of the
      naturally derived colorants provide health benefits. Food scientists frequently
      have the assignment of replacing artificial colorants with natural alternatives.
      This can be challenging, as naturally derived colorants are usually less stable,
      and all desired hues might, in fact, not be obtainable. In this review, the
      chemical and physical properties, limitations, and more suitable applications for
      those colorants that are legally available as substitutes for the synthetic
      colorants are summarized. Issues and challenges for certain foods are discussed,
      and in addition, colorants that may be available in the future are briefly
      described.

PMID- 22385165
TI  - Food safety and organic meats.
AB  - The organic meat industry in the United States has grown substantially in the
      past decade in response to consumer demand for nonconventionally produced
      products. Consumers are often not aware that the United States Department of
      Agriculture (USDA) organic standards are based only on the methods used for
      production and processing of the product and not on the product's safety. Food
      safety hazards associated with organic meats remain unclear because of the
      limited research conducted to determine the safety of organic meat from farm-to
      fork. The objective of this review is to provide an overview of the published
      results on the microbiological safety of organic meats. In addition,
      antimicrobial resistance of microbes in organic food animal production is
      addressed. Determining the food safety risks associated with organic meat
      production requires systematic longitudinal studies that quantify the risks of
      microbial and nonmicrobial hazards from farm-to-fork.

PMID- 22385166
TI  - Functional replacements for gluten.
AB  - Celiac disease (CD) is an immune-mediated disease triggered in genetically
      susceptible individuals by ingested gluten from wheat, rye, barley, and other
      closely related cereal grains. Currently, the only therapy able to normalize the
      clinical and histological manifestation of the disease is a strict and life-long
      gluten-free (GF) diet. The replacement of gluten presents a significant
      technological challenge, as it is an essential structure-building protein, which
      is necessary for formulating high-quality baked goods. The objective of this
      paper is to review some basics about CD, its current prevalence, and the recent
      advances in the preparation of high-quality GF breads using GF flours, starches,
      hydrocolloids, gums, and novel functional ingredients and technologies.

PMID- 22385167
TI  - New interventions against human norovirus: progress, opportunities, and
      challenges.
AB  - Human norovirus (HuNoV) is the leading causative agent of foodborne disease
      outbreaks worldwide. HuNoV is highly stable, contagious, and only a few virus
      particles can cause illness. However, HuNoV is difficult to study because of the
      lack of an efficient in vitro cell culture system or a small animal model. To
      date, there is very limited information available about the biology of HuNoV,
      with most data coming from the study of surrogates, such as HuNoV virus-like
      particle (VLP), murine norovirus (MNV), and feline calicivirus (FCV). High-risk
      foods for HuNoV contamination include seafood, fresh produce, and ready-to-eat
      foods. Currently, there is no effective measure to control HuNoV outbreaks; thus,
      development of food-processing technologies to inactivate HuNoV in these high
      risk foods is urgently needed. Although a VLP-based vaccine induces humoral,
      mucosal, and cellular immunities in animals and currently is in human clinical
      trials, development of other new vaccine candidates, such as live vectored
      vaccines, should be considered. Recent evidence suggests that blockage of virus
      receptor interaction may be a promising antiviral target. To enhance our
      capability to combat this important agent, there is an urgent need to develop
      multidisciplinary, multi-institutional integrated research and to implement food
      virology education and extension programs nationwide.

PMID- 22385168
TI  - Novel natural food antimicrobials.
AB  - Naturally occurring antimicrobial compounds could be applied as food
      preservatives to protect food quality and extend the shelf life of foods and
      beverages. These compounds are naturally produced and isolated from various
      sources, including plants, animals and microorganisms, in which they constitute
      part of host defense systems. Many naturally occurring compounds, such as nisin,
      plant essential oils, and natamycin, have been widely studied and are reported to
      be effective in their potential role as antimicrobial agents against spoilage and
      pathogenic microorganisms. Although some of these natural antimicrobials are
      commercially available and applied in food processing, their efficacy, consumer
      acceptance and regulation are not well defined. This manuscript reviews natural
      antimicrobial compounds with reference to their applications in food when applied
      individually or in combination with other hurdles. It also reviews the mechanism
      of action of selected natural antimicrobials, factors affecting their
      antimicrobial activities, and future prospects for use of natural antimicrobials
      in the food industry.

PMID- 22385169
TI  - The structure of the casein micelle of milk and its changes during processing.
AB  - The majority of the protein in cow's milk is contained in the particles known as
      casein micelles. This review describes the main structural features of these
      particles and the different models that have been used to define the interior
      structures. The reactions of the micelles during processing operations are
      described in terms of the structural models.

PMID- 22385170
TI  - Synthesis and study the analgesic effects of new analogues of ketamine on female
      wistar rats.
AB  - Ketamine (2-o-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, CI-581,
      Ketalar, I), a potent derivative of Phencyclidine (1-[1-phenylcyclohexyl]
      piperidine, CAS 956-90-1, PCP, II), and many of its analogues have shown
      anesthetic and analgesic effects. In this research, new derivatives of I, (2-[p
      methoxybenzylamino]-2-[p-methoxyphenyl] cyclohexanone, ket-OCH3, III), (2-[p
      methylbenzylamino]-2-[p-methoxyphenyl] cyclohexanone, ket-CH3, IV) and their
      intermediates (V-VIIII) were synthesized and the acute and chronic pains of III
      and IV were evaluated on rats using tail immersion (as a model of acute thermal
      pain) and formalin (as a model of acute and chronic chemical pain) tests. The
      results werecompared with ketamine and control (saline) groups. The results
      indicated that in tail immersion and formalin tests, these new derivatives (III
      and IV) were usually effective for decreasing pain on rats.

PMID- 22385171
TI  - Novel gastrin receptor-directed contrast agents - potential in brain tumor
      magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) is presently the method of choice for detection
      of brain tumors. However, MRI alone is not conclusive. As the commonly used
      contrast agents do not bind to the cells and are not taken up into the cells,
      they generally do accumulate in regions where the blood-brain-barrier is
      disrupted. While this can be brain tumors (WHO grade II-III and above), it can
      also be inflammations. A cell-directed contrast agent would be a great asset not
      only to avoid unnecessary brain biopsies, but also to achieve sharper tumor
      margins during intraoperative MRI. The gastrin/cholecystockinin receptor found in
      the brain and the intestinal tract is a potential target for a cell-directed
      contrast agent. The receptor has already been found in human glioma cell lines
      and autocrine stimulation has also been demonstrated for the receptor and its
      ligand gastrin. We coupled the correct and a mutant 17-amino-acid gastrin to
      gadolinium -1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (an MRI
      contrast agent) and rhodamine isothiocyanate (a fluorescent dye). Using confocal
      laser scanning microscopy and magnetic resonance relaxometry experiments we found
      cytoplasmic uptake of the correct gastrin conjugate into human U373 glioma cells.
      Surprisingly, the mutant conjugate was also taken up into the cells in a similar
      pattern, albeit to a lesser degree. Both conjugates showed no cytotoxicity. These
      conjugates show potential for future use in magnetic resonance imaging studies of
      brain tumors after systemic or intraoperative local application. The cytoplasm
      specificity of the conjugates also makes it a potential building block for the
      design of future cytoplasmdirected imaging and therapeutic conjugates.

PMID- 22385172
TI  - Synthesis of a fluorescently labeled compound for the detection of arsenic
      induced apoptotic HL60 cells.
AB  - Arsenic compounds have shown medical usefulness since they proved to be effective
      in causing complete remission of acute promyelocytic leukemia. In this work we
      obtained a fluorescently labeled arsenic compound that can be used with current
      fluorescence techniques for basic and applied research, focused on arsenic
      induced apoptosis studies. This compound is an arsanilic acid bearing a
      covalently linked FITC that was chemically synthesized and characterized by
      fluorescence, UV-Vis, mass and FTIR spectrometry. In addition, we assessed its
      apoptotic activity as well as its fluorescent labeling properties in HL60 cell
      line as a leukemia cell model through flow cytometry. We obtained a compound with
      a 1:1 FITC:arsenic ratio and a 595 m/z, confirming its structure by FTIR. This
      compound proved to be useful at inducing apoptosis in the leukemia cell model and
      labeling this apoptotic cell population, in such a way that the highest FITC
      fluorescence correlated with the highest arsenic amount.

PMID- 22385173
TI  - An in silico stereo-electronic comparison of conventional pyridinium oximes and K
      oximes for organophosphate (OP) poisoning.
AB  - A comparative analysis of stereo-electronic properties of five cholinesterase
      reactivators (pralidoxime (2- PAM), trimedoxime, obidoxime, HI-6, and HLo-7) and
      six "K-oximes" was performed to assess their roles in reactivating OP-inhibited
      phosphorylated serine residue of mouse AChE. Quantum mechanical (QM) calculations
      starting from semiempirical to ab initio levels were sequentially performed with
      hierarchical basis sets to obtain the individual optimized geometry and stereo
      electronic properties of the eleven oximes. Next, solvation effects were computed
      on the optimized structures using two different (PCM and COSMO) QM models.
      Results indicate that properties, such as the distance between the bisquarternary
      nitrogen atoms, surface area, molecular volume, and hydrophilicity have important
      roles in the reactivation of OP-inhibited AChE. Electronic attributes, such as
      the molecular electrostatic potentials and orbital energies were also found to be
      important parameters for reactivation. Nucleophilicity of the oxygen atoms at the
      terminal regions, electrophilicity in the central regions of the oximes, and
      location of the molecular orbitals on aromatic rings have significant roles for
      the experimentally observed reactivations in several OP agents inhibited mouse
      AChE. Analysis of solvation free energy indicates high solute polarization and
      dispersion energies of the oximes to be particularly critical for the tabun-
      inhibited mouse AChE, whereas lower values of these properties favor reactivation
      against other OP agents, such as soman, sarin and cyclosarin. Feature mappings of
      our recently reported pharmacophore model were also observed to be consistent
      with the above observed electronic properties. In silico toxicity evaluation on
      these oximes predicts the Koximes to have somewhat higher oral toxicity compared
      to the other bispyridinium oximes.

PMID- 22385174
TI  - Synthesis and preliminary antihyperlipidaemic activities evaluation of
      andrographolide derivatives.
AB  - Recent studies indicated that andrographolide was a potential antihyperlipidaemic
      therapeutic agent. In the paper, the synthesis of a series of andrographolide
      derivatives was described and their antihyperlipidaemic activities were evaluated
      in vivo. As compared with TG, TC, HDL-C and LDL-C concentrations, some of the
      derivatives exhibited better antihyperlipidaemic effects than positive control
      atromide. Therein, compound 6i, which was the most potent compound, could serve
      as a new lead for further development of antihyperlipidaemic agents.

PMID- 22385175
TI  - Synthesis and cytotoxic evaluation of quinazolin-4(3H)-one derivatives bearing
      thiocarbamate, thiourea or N-methyldithiocarbamate side chains.
AB  - We have previously found that the dithiocarbamate derivatives of quinazolin-4(3H)
      one could act as cytotoxic agents against a panel of human tumor cell lines. To
      investigate the contribution of dithiocarbamate moiety to the cytotoxic activity,
      three series of novel quinazolin-4(3H)-one derivatives bearing thiocarbamate,
      thiourea or Nmethyldithiocarbamate side chains were synthesized and tested for
      their cytotoxic activity against human cancer cell lines A549, MCF-7, HeLa, HT29
      and HCT-116 by MTT assay. The results showed that transformation of the
      dithiocarbamate moiety in lead compound I to thiocarbamate or thiourea led to a
      decrease or loss of cytotoxic activity. Some N-alkylated analogs of lead compound
      II preferentially inhibited the proliferation of A549 cells, although their
      potencies were not improved in comparison with the unalkylated counterparts. The
      structure-activity relationship obtained in this research will be beneficial for
      further synthesis and discovery of effective cytotoxic agents.

PMID- 22385176
TI  - 2D Chemometrics analyses of tetrahydroquinoline and ethylenediamine derivatives
      with antimalarial activity.
AB  - Malaria, one of the most widespread and deadly infectious diseases continues to
      kill over 1 million people every year. This scenario is getting even worse as P.
      falciparum develops resistance to existing drugs. Thus, there is an imperative
      need for novel and more effective antimalarials. Farnesyltransferase (PFT)
      appears to be a promising therapeutic target to development of antimalarial drugs
      and many analogs of PFT inhibitors have proved active against P. falciparum. In
      order to shed some light on the structure-activity relationships of 192
      tetrahydroquinoline and ethylenediamine derivatives that are active against
      P.falciparum, exploratory analysis as well as classical and hologram QSAR
      strategies were employed. No global QSAR could be developed for the whole
      dataset, instead local QSAR models were developed for 118 compounds (classical
      QSAR r2=0.78, q2=0.75, r2 pred= 0.77 with 2 PCs; HQSAR r2=0.82, q2=0.72, r2 pred=
      0.79 with 3 PCs) and 74 compounds (r2=0.79, q2=0.74, r2 pred= 0.57 with 2PCs;
      r2=0.86, q2=0.77, r2 pred= 0.75 with 4 PCs) using partial least square (PLS)
      regression. Furthermore, the careful and integrated analysis of contribution maps
      and regression vector suggest that these inhibitors might have dissimilar
      requirements to their biological activity.

PMID- 22385177
TI  - Design, synthesis & biological evaluation of some novel quinazolinone scaffolds.
AB  - In an effort to discover new candidates with improved antimicrobial activities,
      we synthesized and studied invitro antimicrobial activities of various series of
      3-((thiophen-2-yl)-ethyl)-2-(styryl)-quinazolin-4(3H)-one (3a-3g) and N1
      (substituted aryl)-N3-[3-((3,4-dimethoxy phenyl-2-yl)-ethyl)-4(3H)-quinazolone-2
      yl]-acetonyl semicarbazides (7a-7j) with an intent to overcome multiple drug
      resistance to the pathogenic strains and to retain psychological action to
      develop novel class of antibacterial agents. The structure of newly synthesized
      scaffolds has been affirmed on the basis of FTIR, 1H NMR, 13C NMR, mass and
      elemental analysis. All the final scaffolds have been subjected to in vitro
      antimicrobial screening against two Gram (+Ve) bacteria (S. aureus, B. subtilis),
      two Gram (-Ve) bacteria (E. coli, S.typhi) and two fungal strains (C. albicans,
      A. niger) using the broth micro-dilution method.

PMID- 22385178
TI  - Synthesis and in vivo antimalarial evaluation of novel hydroxyethylamine
      derivatives.
AB  - A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S
      )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for
      their in vivo antimalarial activity in mice. Compound 4g presented better
      activity then the reference artesunate in percentage of inhibition of parasitemia
      in treated P. berghei-infected mice and compare to the activity of artesunate in
      the survival of mice 14 days after infection. In addiction, no hemolytic activity
      was found, which supports that inhibition of parasitemia is due to antimalarial
      activity. The compound 4g inhibited the differentiation to schizonts suggesting
      that parasite metabolism is a possible target of 4g. These results indicate that
      this class of compound possesses promising perspectives for the development of
      new antimalarial drugs.

PMID- 22385179
TI  - A pharmacophore model specific to active site of CYP1A2 with a novel molecular
      modeling explorer and CoMFA.
AB  - Comparative molecular field analysis (CoMFA) is a widely used 3D-QSAR method by
      which we can investigate the potential relation between biological activity of
      compounds and their structural features. In this study, a new application of this
      approach is presented by combining the molecular modeling with a new developed
      pharmacophore model specific to CYP1A2 active site. During constructing the
      model, we used the molecular dynamics simulation and molecular docking method to
      select the sensible binding conformations for 17 CYP1A2 substrates based on the
      experimental data. Subsequently, the results obtained via the alignment of
      binding conformations of substrates were projected onto the active- site
      residues, upon which a simple blueprint of active site was produced. It was
      validated by the experimental and computational results that the model did
      exhibit the high degree of rationality and provide useful insights into the
      substrate binding. It is anticipated that our approach can be extended to
      investigate the protein-ligand interactions for many other enzyme-catalyzed
      systems as well.

PMID- 22385180
TI  - Molecular dynamics simulations of CYP2E1.
AB  - CYP2E1, as a member of the cytochrome P450s (CYPs) super-family, is in charge of
      six percent drug metabolism involving a diversity of drugs distinct in structures
      and chemical properties, such as alcohols, monocyclic compounds (e.g.,
      acetaminophen, benzene, p-nitrophenol), bicyclic heterocycles (e.g., coumarin,
      caffeine) and even fatty acids. The aromatic molecules form a vital species
      catalyzed by CYP2E1. To investigate the mechanism of metabolizing a diversity of
      aromatic molecules, five representative aromatic substrates were selected: (1)
      benzene, the non-polar simple ring; (2) aniline, the monocyclic substrate with
      smallest substitution on the phenyl ring; (3) acetaminophen, a large monocyclic
      substrate with highly active reactivity; (4) chlorzoxazone, and (5) theophylline,
      the bicyclic substrates with low or high catalytic activities. They were docked
      into X-ray structure of CYP2E1, after which all-atom molecular dynamics
      simulations of 5 ns were performed on each model. It was found that the active
      site interact with the aromatic substrates mainly through pi-pi stacking,
      supplied by five hydrophobic phenylalanines in the active site. Our simulations
      also illustrated the specific movement of different kinds of aromatic substrates
      in the pocket. Small monocyclic substrates show highly frequent self-rotation and
      limited translation movement. Substrates with single catalytic position are less
      movable in the pocket than substrates with multiple products. All these findings
      are quite useful for understanding the catalytic mechanism of CYP2E1, stimulating
      novel strategies for conducting further mutagenesis studies for specific drug
      design.

PMID- 22385181
TI  - Synthesis and anticancer activity of novel benzimidazole and benzothiazole
      derivatives against HepG2 liver cancer cells.
AB  - Most of cancer chemotherapeutics and chemopreventives exert their effects by
      triggering apoptotic cell death. In this study, novel benzimidazole and
      benzothiazole derivatives have been synthesized to investigate their effects on
      HepG2 liver cancer cell lines after initial screening study. A dose response
      curve was constructed and the most active derivatives were further studied for
      apoptotic analysis. Six active benzimidazole derivatives (8, 9, 10, 12, 13 and
      14) significantly induced apoptosis compared to control group. Two compounds 10
      and 12 induced apoptosis by arresting cells in G1 phase of cell cycle which is
      confirmed by increased expression level of p21. The activity of caspase-3 which
      is well known as one of the key executioners of apoptosis was determined in the
      presence and absence of the tested derivatives. Our results indicated that
      compounds 10 and 12 significantly increased caspase-3 activity compared to
      control group. Moreover, a docked pose of compounds 10 and 12 was obtained bound
      to caspase-3 active site using Molecular Operating Environment module. This study
      demonstrated that benzimidazole derivatives 10 and 12 provoke cytotoxicity and
      induced apoptosis in liver cancer cells HepG2.

PMID- 22385182
TI  - Identification of structural features for 4-methyl-3-(6-[phenyl methylene] amino}
      pyridine-3-yl)-2H chromen-2-one derivatives as clotting factor Xa inhibitors.
AB  - Anticoagulants are used to prevent the formation and extension of blood clots in
      various disorders as prophylactic agents for thrombo-embolic disorders. Designing
      of specific inhibitors against molecular targets that play a pivotal role in the
      coagulation cascade is indispensable. Clotting Factor Xa is one such attractive
      target for the design of new oral anticoagulants because of the unique role
      factor Xa plays in the coagulation cascade as a connection between the extrinsic
      and intrinsic pathways. Application of computational techniques in drug discovery
      process helps in identifying parameters which can lead to achieve better
      pharmacological profile. The docking interactions and QSAR studies performed on
      series of 4-methy-3-(6-[phenyl methylene] amino} pyridine-3-yl)-2H chromen-2-one
      derivatives provide significant insights for designing of better ligands as
      anticoagulants.

PMID- 22385183
TI  - Structure-activity relationships of 2-benzylsulfanylbenzothiazoles: synthesis and
      selective antimycobacterial properties.
AB  - A set of 2-benzylsulfanyl derivatives of benzothiazole was synthesized and
      evaluated for antimicrobial and cytotoxic activities. The biological screening on
      antimicrobial activity against a panel of Gram-positive and Gram-negative
      bacteria, yeasts and fungi identified benzylsulfanyl derivatives of benzothiazole
      as selective inhibitors of mycobacteria. The lead compounds in the set, dinitro
      derivatives exhibited significant activity against sensitive and multidrug
      resistant strains of M. tuberculosis and low cytotoxicity. The QSAR study
      indicated that the antituberculotic activity is connected with LUMO and HOMO
      energies. The lower lipophilicity and the increased size of the molecule
      contribute to antituberculotic activity. Thus, dinitrobenzylsulfanyl derivatives
      of benzothiazole represent promising smallmolecule synthetic antimycobacterials.

PMID- 22385184
TI  - Facile synthesis and biological evaluation of novel symmetrical biphenyls as
      antitumor agents.
AB  - As a continuation to our previous work in developing anticancer agents, eighteen
      symmetrical biphenyl derivatives structurally related to taspine were synthesized
      and evaluated in vitro and in vivo. All the compounds were prepared with varied
      substitutions in the phenyl ring of aniline moiety. The cytotoxicity and
      anticancer activity of biphenyls was evaluated against various human tumor and
      normal cell line. Antiproliferative assays indicated that some of them exhibited
      potent anticancer activity. The potent antiproliferative activity of these
      compounds against ECV304 suggested that these biphenyls could be served as
      antiangiogenic agents. The highly active compound (2) also exhibited potent
      growth inhibition against cancer cell lines in vivo. Our findings demonstrated
      that these symmetrical biphenyl derivatives would be a promising candidate as
      novel anticancer agents.

PMID- 22385185
TI  - Optimization of important early ADME(T) parameters of NADPH oxidase-4 inhibitor
      molecules.
AB  - Through their reactive oxygen species (ROS) producing function, NADPH oxidase
      (NOX) enzymes have been linked to several oxidative stress related diseases. In
      our recently published paper [1] we have already shown the NOX4 inhibitory effect
      of diverse, molecule sub-libraries and their biological importance. We also
      presented our work connected to potential anti-tumour molecules and the
      relationship between their biological activity and physico-chemical properties
      [2]. As an extension of these studies further physico-chemical and biological
      investigation has been carried out on a molecule group included NOX4 inhibitory
      chromanone compounds. Here we describe the optimization of early ADME(T)
      parameters determining lipophilicity, phospholipophilicity and permeability
      linked to structure-activity relationship. We prove that optimal lipo- and
      phospholipophilicty can be also determined in case of NOX4 inhibitors and a
      comparison will be made between the chemically similar isochromanone and
      chromanone molecular libraries. It will be also shown how to predict the effect
      of different substituents on permeability, lipo- and phospholipophilicity and
      also the biological differences between anti-tumour molecules and NOX4 inhibitors
      according to their penetration ability.

PMID- 22385186
TI  - Anticancer agents for treatment of tumors in the central nervous system by
      correspondent substituent substitution and elucidation by pattern recognition
      methods.
AB  - Within the United States, primary brain tumors account for 20 to 25 percent of
      all pediatric cancers. Chemotherapy utilizing a nitrosourea, notably semustine
      (MeCCNU) and carmustine (BCNU), has shown significant success in the treatment of
      tumors found in the central nervous system. In silico optimization of molecular
      properties by substituent substitution that is followed by pattern recognition
      analysis is utilized in this study to develop 14 novel anti-cancer drugs for the
      treatment of malignant cancers of the central nervous system. These 14 agents
      exhibit molecular properties that are suitable for penetration through the blood
      brain barrier (BBB). All 14 agents are nitrosoureas having values of Log P
      ranging from 2.188 to 2.942, and having a constant total of 5 oxygens and
      nitrogens with zero violations of the Rule of 5 which indicates favorable
      bioavailability. Value of Log BB (Log [Cbrain/Cblood]) for these agents does not
      vary from - 0.441 (BB value of 0.362). The formula weight of the agents is highly
      correlated to molecular volume (r= 0.9848) and total number of atoms (r= 0.9948),
      but not correlated to number of rotatable bonds (r= 0.1814). Analysis of
      similarity (ANOSIM) indicated that all 14 new constructs are similar to the
      parent compound semustine. The Log P value for all 14 agents predicts favorable
      attributes for penetrating the BBB. Multiple regression analysis established that
      number of atoms, number of rotatable bonds, and molecular volume are strong
      prognosticators for molecular weight of this assemblage of pharmaceuticals. This
      study attests to the efficacy of in silico optimization of molecular substituents
      followed by pattern recognition analysis to develop new drug designs based on a
      successful nitrosourea framework for the treatment of malignant tumors of the
      brain.

PMID- 22385187
TI  - Small molecule hydrazide agents to inhibit growth and proliferation of
      mycobacterium tuberculosis.
AB  - Four novel drug designs for the treatment of Mycobacterium tuberculosis are
      analyzed and shown to prevent the growth and proliferation of this dangerous
      bacteria. All four agents, designated A, B, C, and D, are hydrazide type
      compounds, where D has three hydrazide functional groups. Agents B and C have a
      halogenated aromatic ring substituent, while A contains a pyridine ring.
      Pharmaceutical properties such as Log P, polar surface area, and violations of
      the Rule of 5 are determined for all agents. The Polar surface area for these
      four agents ranged from 55.121 A2 to 165.363 A2 and Log P values for A, B, C, and
      D were determined at -0.916, 0.95, 0.974, and -4.921, respectively. Drug designs
      A, B, and C show zero violations of the Rule of 5, where D exhibits only one
      violation, which are outcomes describing favorable bioavailability. Values of
      polar surface area for A, B, and C affirm an intestinal absorption of greater
      than 60% as well as the potential for crossing the blood brain barrier for
      targeting bacterial meningitis of the central nervous system. Interaction with
      Mycobacterium tuberculosis was monitored over a 14 day interval with agents at
      known concentration. Agents A, B, C, and D elicited more than 60% inhibition of
      bacterial growth by day 14 at concentrations of as little as 30 micrograms/
      milliliter. All agents reduced bacteria survival to less than 60% by day 7 of
      culture. The inhibition of bacterial growth induced by agents A, B, C, and D was
      comparable to that of isoniazid. K-means cluster analysis of descriptors
      determined isoniazid most similar to agents A, B, and C. Other characteristics of
      these small hydrazide compounds render supportive evidence for an efficacious
      clinical application.

PMID- 22385189
TI  - Mean platelet volume in Korean patients with acute ischemic stroke: a gender
      difference.

PMID- 22385188
TI  - Design, synthesis and evaluation of unique 2,4,5-triaryl imidazole derivatives as
      novel potent aspartic protease inhibitors.
AB  - The 2,4,5-triaryl imidazole derivatives (API) were designed, screened and
      characterized kinetically & thermodynamically against Pepsin and their activity
      was also tested on the in silico platform. The docking studies of API with Pepsin
      show that these are novel and unique inhibitors of Aspartic protease. Drug like
      properties of these compounds were validated in silico based on Lipinski's rule
      of Five by calculating ClogP, LogS, H-bond acceptors, H-Bond donors, rotational
      bonds, PSA, PB and BBB values. The Et/Ki and Et/Km values of API show that they
      follow the Michaelis-Menten kinetics. The binding of inhibitors with proteases
      was explained by using Van't Hoff plot and thermodynamic parameters viz. free
      energy (DeltaG), Entropy (DeltaS) and Enthalpy (DeltaH). The Van't Hoff analysis
      showed that the value of Ki decreases with increase in temperature and the
      binding of the inhibitor are entropically driven. API act as new potent aspartic
      protease inhibitors with Ki, for Pepsin, ranges from 3.7 uM to 16.7 uM. Strong
      hydrophobic groups at C-4 & C-5 position in API favor binding of inhibitors with
      Pepsin. Experiments also showed that among C-2 aryl substituted imidazole, a 4
      substitution on aryl ring is preferred and less polar substituent makes the
      molecule more active whereas polar substituents at 2-position on C-2 aryl ring
      makes the molecule less active. The docking studies of API with Pepsin further
      intensify and validate our results.

PMID- 22385190
TI  - Three cases of acute gastroenteritis caused by high-level macrolideresistant
      Campylobacter: drug resistance mechanisms and clinical characteristics.
AB  - We report 3 cases of acute gastroenteritis caused by high-level macrolide
      resistant Campylobacter. The clinical characteristics of patients were studied,
      and the rplD, rplV, and 23S rRNA domain V genes were sequenced to detected
      resistance-related mutations.

PMID- 22385191
TI  - Are high drug loading nanoparticles the next step forward for chemotherapy?

PMID- 22385192
TI  - Challenges posed by the scale-up of nanomedicines.

PMID- 22385194
TI  - Novel resonating nanowire arrays function as highly sensitive biosensors.

PMID- 22385195
TI  - Nanostructures for sensors and analytical systems.
AB  - Professor Harold Craighead attended the University of Maryland (MD, USA) where he
      received his Bachelor of Science Degree in Physics. He moved to Cornell
      University (NY, USA) for his PhD in Physics, which he completed in 1980. He
      subsequently worked as a member of technical staff in the Device Physics Research
      Department at Bell Laboratories (NJ, USA) until 1984 when he joined Bellcore to
      form and manage the Quantum Structures research group. Professor Craighead
      returned to Cornell University as a Professor in the School of Applied and
      Engineering Physics. He became the Director of the National Nanofabrication
      Facility at Cornell and remained in this post until 1995. Professor Craighead was
      also the Director of the School of Applied and Engineering Physics and the
      founding Director of the Nanobiotechnology Center. In 2001, he was appointed the
      Interim Dean of the College of Engineering. He was awarded the Charles W Lake Jr
      Professorship of Engineering at Cornell University. Professor Craighead was
      elected to the National Academy of Engineering in 2007 and has authored over 340
      papers and book chapters, as well as 51 issued patents.

PMID- 22385196
TI  - Kindling translational cancer nanotechnology research.

PMID- 22385197
TI  - Chemotherapy targeting by DNA capture in viral protein particles.
AB  - AIM: This study tests the hypothesis that DNA intercalation and electrophilic
      interactions can be exploited to noncovalently assemble doxorubicin in a viral
      protein nanoparticle designed to target and penetrate tumor cells through ligand
      directed delivery. We further test whether this new paradigm of doxorubicin
      targeting shows therapeutic efficacy and safety in vitro and in vivo. MATERIALS &
      METHODS: We tested serum stability, tumor targeting and therapeutic efficacy in
      vitro and in vivo using biochemical, microscopy and cytotoxicity assays. RESULTS:
      Self-assembly formed approximately 10-nm diameter serum-stable nanoparticles that
      can target and ablate HER2+ tumors at >10* lower dose compared with untargeted
      doxorubicin, while sparing the heart after intravenous delivery. The targeted
      nanoparticle tested here allows doxorubicin potency to remain unaltered during
      assembly, transport and release into target cells,while avoiding peripheral
      tissue damage and enabling lower, and thus safer, drug dose for tumor killing.
      CONCLUSION: This nanoparticle may be an improved alternative to chemical
      conjugates and signal-blocking antibodies for tumor-targeted treatment.

PMID- 22385198
TI  - Novel dual-control poly(N-isopropylacrylamide-co-chlorophyllin) nanogels for
      improving drug release.
AB  - AIM: How to overcome insufficient drug release is an important issue in the drug
      delivery system. MATERIALS & METHODS: Here, a novel temperature and UV dual
      control poly(N-isopropylacrylamide [PNIPAM]-co-chlorophyllin) nanogel was
      prepared via the surfactant-free emulsion polymerization. RESULTS: The
      introduction of hydrophilic chlorophyllin to the PNIPAM chain backbone led to a
      narrow size of poly[NIPAM-co-CHLN nanogel (D ~180 nm) confirmed by atomic force
      microscopy and transmission electron microscopy. This nanogel had a lower
      critical solution temperature (~35 degrees C), observed by dynamic laser light
      scattering. After the phase transition, the size under UV light (50 nm) was much
      smaller than that induced by temperature (90 nm). The inhomogeneous collapse was
      attributed to the temperature-gradient generated from the gel surface to the core
      with a surrounding dense PNIPAM layer. The obstacles that strongly inhibited 5
      fluorouracil release was successfully overcome by light irradiation via a large
      drug diffusion coefficient. CONCLUSION: Consequently, the novel dual functional
      nanogel is potent for improving the drug-release profile.

PMID- 22385199
TI  - Tapping the potential of quantum dots for personalized oncology: current status
      and future perspectives.
AB  - Cancer is one of the most serious health threats worldwide. Personalized oncology
      holds potential for future cancer care in clinical practice, where each patient
      could be delivered individualized medicine on the basis of key biological
      features of an individual tumor. One of the most urgent problems is to develop
      novel approaches that incorporate the increasing molecular information into the
      understanding of cancer biological behaviors for personalized oncology. Quantum
      dots are a heterogeneous class of engineered fluorescent nanoparticles with
      unique optical and chemical properties, which make them promising platforms for
      biomedical applications. With the unique optical properties, the utilization of
      quantum dot-based nanotechnology has been expanded into a wide variety of
      attractive biomedical applications for cancer diagnosis, monitoring,
      pathogenesis, treatment, molecular pathology and heterogeneity in combination
      with cancer biomarkers. Here, we focus on the clinical application of quantum dot
      based nanotechnology in personalized oncology, covering topics on individualized
      cancer diagnosis and treatment by in vitro and in vivo molecular imaging
      technologies, and in-depth understanding of the biological behaviors of tumors
      from a nanotechnology perspective. In addition, the major challenges in
      translating quantum dot-based nanotechnology into clinical application and
      promising future directions in personalized oncology are also discussed.

PMID- 22385200
TI  - Advances in molecular imaging: targeted optical contrast agents for cancer
      diagnostics.
AB  - Over the last three decades, our understanding of the molecular changes
      associated with cancer development and progression has advanced greatly. This has
      led to new cancer therapeutics targeted against specific molecular pathways; such
      therapies show great promise to reduce mortality, in part by enabling physicians
      to tailor therapy for patients based on a molecular profile of their tumor.
      Unfortunately, the tools for definitive cancer diagnosis - light microscopic
      examination of biopsied tissue stained with nonspecific dyes - remain focused on
      the analysis of tissue ex vivo. There is an important need for new clinical tools
      to support the molecular diagnosis of cancer. Optical molecular imaging is
      emerging as a technique to help meet this need. Targeted, optically active
      contrast agents can specifically label extra- and intracellular biomarkers of
      cancer. Optical images can be acquired in real time with high spatial resolution
      to image-specific molecular targets, while still providing morphologic context.
      This article reviews recent advances in optical molecular imaging, highlighting
      the advances in technology required to improve early cancer detection, guide
      selection of targeted therapy and rapidly evaluate therapeutic efficacy.

PMID- 22385201
TI  - Nanoparticles for cancer therapy using magnetic forces.
AB  - The term 'nanomedicine' refers to the use of nanotechnology in the treatment,
      diagnosis and monitoring of diseases. Magnetic drug targeting is a particularly
      promising application in this field. The goal of the carrier systems involved is
      to achieve active enrichment of effective substances in diseased tissue. Numerous
      nanosystems can be used as carriers, but magnetic iron oxide nanoparticles are
      particularly important. On the one hand, the particles serve as carriers for the
      active substance, while on the other hand they can also be visualized using
      conventional imaging techniques and can therefore be used for 'theranostic'
      purposes. They can also be used in hyperthermia, another important pillar of
      nanomedicine. Both procedures are intended to lead to specific forms of
      treatment, which is of medical and economic relevance in view of the increasing
      numbers of cancer patients worldwide. This study offers a brief overview of
      current developments in medical applications for magnetic nanoparticles in cancer
      therapy.

PMID- 22385204
TI  - In Vivo modulation of the innate response to pneumovirus by type-I and -III
      interferon-induced Bos taurus Mx1.
AB  - The respiratory syncytial virus (RSV) is a major pathogen of the human species.
      This pneumovirus is a prominent cause of airway morbidity in children and
      maintains an excessive hospitalization rate despite decades of research. As
      involvement of a genetic vulnerability is a possibility supported by recent data,
      we addressed the question of whether the Mx gene products, the typical target of
      which consists in single-stranded negative-polarity RNA viruses, could alter the
      course of pneumovirus-associated disease in vivo. Wild-type and Bos taurus Mx1
      expressing transgenic FVB/J mice were inoculated with the mouse counterpart and
      closest phylogenetic relative of RSV, pneumonia virus of mice. Survival data and
      follow-up of body weight, histological scores, lung virus spread, and lung viral
      load unequivocally showed that the viral infection was severely repressed in Mx
      transgenic mice, thus suggesting that pneumoviruses belong to the antiviral
      spectrum of mammalian Mx GTPases. Elucidating the underlying mechanisms at the
      molecular level could reveal critical information for the development of new anti
      RSV molecules.

PMID- 22385203
TI  - Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human
      bronchial epithelial cells compromised by cigarette smoke in vitro.
AB  - BACKGROUND AND PURPOSE: Mucociliary malfunction occurs in chronic obstructive
      pulmonary disease (COPD) and compromised functions of ciliated bronchial
      epithelial cells may contribute to this. Cigarette smoke, a major risk factor for
      COPD, impairs ciliary beat frequency (CBF). cAMP augments CBF. This in vitro
      study addressed, in differentiated, primary human bronchial epithelial cells,
      whether roflumilast N-oxide, a PDE4 inhibitor, (i) augments CBF; (ii) prevents
      the reduction in CBF induced by cigarette smoke extract (CSE); and (iii) protects
      against the loss of the ciliated phenotype following long-term CSE exposure.
      EXPERIMENTAL APPROACH: Air-liquid interface cultured human bronchial epithelial
      cells were incubated with roflumilast N-oxide and exposed to CSE. CBF was
      assessed by digital high speed video microscopy (DHSV). Ciliated cells were
      characterized by beta-tubulin IV staining and analyses of Foxj1 and Dnai2 mRNA
      and protein (real-time quantitative PCR, Western blotting). KEY RESULTS:
      Roflumilast N-oxide concentration-dependently triggered a rapid and persistent
      increase in CBF and reversed the decrease in CBF following CSE. Long-term
      incubation of bronchial epithelial cells with CSE resulted in a loss in ciliated
      cells associated with reduced expression of the ciliated cell markers Foxj1 and
      Dnai2. The PDE4 inhibitor prevented this loss in the ciliated cell phenotype and
      the compromised Foxj1 and Dnai2 expression. The enhanced release of IL-13
      following CSE, a cytokine that diminishes the proportion of ciliated cells and in
      parallel, reduces Foxj1 and Dnai2, was reversed by roflumilast N-oxide.
      CONCLUSION AND IMPLICATIONS: Roflumilast N-oxide protected differentiated human
      bronchial epithelial cells from reduced CBF and loss of ciliated cells following
      CSE.

PMID- 22385205
TI  - Influenza virus interferon-inducing particle efficiency is reversed in avian and
      mammalian cells, and enhanced in cells co-infected with defective-interfering
      particles.
AB  - Naturally selected variants of influenza virus encoding truncated NS1 proteins
      were tested in chickens as candidate live-attenuated influenza vaccines. Their
      effectiveness correlated with the amount of interferon (IFN) induced in chicken
      cells. Effective variants induced large amounts of IFN and contained
      subpopulations with high ratios of defective-interfering particles:IFN-inducing
      particles (DIP:IFP). Ineffective variants induced less IFN and contained lower
      ratios of DIP:IFP. Unexpectedly, there was a reversal of phenotypes in mammalian
      cells. Variants that induced low amounts of IFN and had low DIP:IFP ratios in
      chicken cells were excellent IFN inducers with high DIP:IFP ratios in mammalian
      cells, and vice versa. The high DIP:IFP ratios and computer-simulated dynamics of
      infection suggested that DIP, as an individual particle, did not function as an
      IFP. The higher efficiency of IFPs in the presence of DIPs was attributed to
      reduced amounts of newly synthesized viral polymerase known to result from out
      competition by defective-interfering RNAs, and the subsequent failure of that
      polymerase to turn-off cellular mRNA transcription-including IFN-mRNA.

PMID- 22385206
TI  - Effect of photodynamic therapy on inflammatory acne using 3% liposomal 5
      aminolevulinic acid emulsion and intense-pulsed light: A pilot study.

PMID- 22385207
TI  - Five-year change of periodontal diseases in the Study of Health in Pomerania
      (SHIP).
AB  - AIM: To assess the extent of remission and progression of periodontal diseases
      among adults in a Northeast German Region. MATERIALS AND METHODS: The Study of
      Health in Pomerania (SHIP) is a population-based cohort study with baseline
      examinations conducted in 1997-2001 and 5-year-follow-up in 2002-2006. The study
      comprised 2558 subjects aged 20-81 years. Periodontal status was assessed by
      probing depth (PD) and attachment level (AL), measured at four surfaces per
      tooth, half-mouth. An event was defined as AL progression or remission of >=3 mm
      on >=2 sites. RESULTS: Average change in mean AL (mean PD) was 0.10 mm (-0.05 mm)
      during follow-up, equalling 0.02 mm/year (-0.01 mm/year). Adjusted for gender and
      follow-up time, change in mean AL was significantly higher in 20-29- and 60-69
      year-old patients compared with 50-59-year-old patients (p < 0.05). 6.5 (7.5)
      events of progression (remission) in AL per 100 person-years were observed. In
      multivariate models, risk factors for progression comprised current smoking,
      middle or low education, being single or divorced and diabetes (p < 0.05).
      Enhanced progressive attachment loss seen in 20-29- and 60-81-year-old patients
      was explained through unfavourable risk factors distributions. CONCLUSIONS:
      Periodontal progression was moderate. Periodontal prophylaxis and motivation to
      reduce risk factors should especially be addressed to patients having
      unfavourable risk factor distributions.

PMID- 22385208
TI  - On the structural origin of the catalytic properties of inherently strained
      ultrasmall decahedral gold nanoparticles.
AB  - A new mechanism for reactivity of multiply twinned gold nanoparticles resulting
      from their inherently strained structure provides a further explanation of the
      surprising catalytic activity of small gold nanoparticles. Atomic defect
      structural studies of surface strains and quantitative analysis of atomic column
      displacements in the decahedral structure observed by aberration corrected
      transmission electron microscopy reveal an average expansion of surface nearest
      neighbor distances of 5.6%, with many strained by more than 10%. Density
      functional theory calculations of the resulting modified gold d-band states
      predict significantly enhanced activity for carbon monoxide oxidation. The new
      insights have important implications for the applications of nanoparticles in
      chemical process technology, including for heterogeneous catalysis.

PMID- 22385209
TI  - Electrostatic effects of mutations of Ras glutamine 61 measured using vibrational
      spectroscopy of a thiocyanate probe.
AB  - Mutations of human oncoprotein p21(Ras) (hereafter Ras) at glutamine 61 are known
      to slow the rate of guanosine triphosphate (GTP) hydrolysis and transform healthy
      cells into malignant cells. It has been hypothesized that this glutamine plays a
      role in the intrinsic mechanism of GTP hydrolysis by interacting with an active
      site water molecule that electrostatically stabilizes the formation of the
      charged transition state at the gamma-phosphate during hydrolysis. We have tested
      the interactions between amino acids at this position and water by measuring
      changes in the electrostatic field experienced by a nitrile probe positioned near
      Ras Q61 using vibrational Stark effect (VSE) spectroscopy. We mutated this
      glutamine to every amino acid except cysteine and proline and then incubated
      these mutants with a Ral guanine nucleotide dissociation stimulator (Ral)
      containing the I18C mutation that was chemically labeled with a thiocyanate
      vibrational spectroscopic probe. The formation of the docked Ras Q61X-labeled Ral
      complex was confirmed by measurement of the dissociation constant of the
      interaction. We measured the absorption energy of this nitrile to determine any
      differences in electrostatic environment in the immediate vicinity of the
      thiocyanate probe between wild type and mutants of Ras. For each Ras Q61X mutant,
      we correlate the change in electrostatic field at position 61 with the solvent
      accessible surface area of polar components of the mutant side chain determined
      from a Boltzmann-weighted ensemble of structures, as well as the residue's
      hydration potential. These results support the hypothesis that the role of Ras
      Q61 is to stabilize water in or near the active site during GTP hydrolysis. The
      substantial effect that nonpolar side chains of Ras Q61X have on the absorption
      energy of the thiocyanate must be investigated with further experiments.

PMID- 22385210
TI  - Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse
      treatment.
AB  - INTRODUCTION AND AIMS: Cigarette smoking occurs frequently among individuals with
      methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested
      that the common co-abuse of MA and cigarettes represents a pharmacologically
      meaningful pattern. METHODS: The present study is a secondary analysis of a
      randomised, placebo-controlled trial of bupropion treatment for MA dependence
      (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach
      assessed the efficacy of bupropion for reducing MA use separately among smokers
      and non-smokers. Among smokers, relations between cigarettes smoked and MA use
      were assessed. RESULTS: Smoking status did not affect treatment responsiveness in
      either the bupropion condition or the placebo condition. In the placebo
      condition, increased cigarette use was associated with an increased probability
      of MA use during the same time period. This effect was not observed in the
      bupropion condition. DISCUSSION AND CONCLUSIONS: Initial smoking status did not
      impact treatment outcomes. Among smokers, results suggest that bupropion may
      dissociate cigarette and MA use. The effect was modest and a precise
      pharmacological mechanism remains elusive. Cholinergic systems may be relevant
      for MA use outcomes. Future studies should continue to assess the role of smoking
      in MA treatment outcomes.

PMID- 22385211
TI  - Enzymatic conversion of epsilon-hexachlorocyclohexane and a
      heptachlorocyclohexane isomer, two neglected components of technical
      hexachlorocyclohexane.
AB  - alpha-, beta, gamma-, and delta-Hexachlorocyclohexane (HCH), the four major
      isomers of technical HCH, are susceptible to biotic transformations, whereby only
      alpha- and gamma-HCH undergo complete mineralization. Nevertheless, LinA and LinB
      catalyzing HCl elimination and hydrolytic dehalogenations, respectively, as
      initial steps in the mineralization also convert beta- and delta-HCH to a variety
      of mainly hydroxylated metabolites. In this study, we describe the isolation of
      two minor components of technical HCH, epsilon-HCH, and heptachlorocyclohexane
      (HeCH), and we present data on enzymatic transformations of both compounds by two
      dehydrochlorinases (LinA1 and LinA2) and a haloalkane dehalogenase (LinB) from
      Sphingobium indicum B90A. In contrast to reactions with alpha-, gamma-, and delta
      HCH, both LinA enzymes converted epsilon-HCH to a mixture of 1,2,4-, 1,2,3-, and
      1,3,5-trichlorobenzenes without the accumulation of pentachlorocyclohexene as
      intermediate. Furthermore, both LinA enzymes were able to convert HeCH to a
      mixture of 1,2,3,4- and 1,2,3,5-tetrachlorobenzene. LinB hydroxylated epsilon-HCH
      to pentachlorocyclohexanol and tetrachlorocyclohexane-1,4-diol, whereas
      hexachlorocyclohexanol was the sole product when HeCH was incubated with LinB.
      The data clearly indicate that various metabolites are formed from minor
      components of technical HCH mixtures. Such metabolites will contribute to the
      overall toxic potential of HCH contaminations and may constitute serious, yet
      unknown environmental risks and must not be neglected in proper risk assessments.

PMID- 22385212
TI  - Leishmania strains causing self-healing cutaneous leishmaniasis have greater
      susceptibility towards oxidative stress.
AB  - The survival of Leishmania parasites within macrophages is influenced by
      generation of free radicals. To establish whether generation of free radicals
      influenced chemotherapeutic response, promastigotes from isolates causing self
      healing or delayed/non-self-healing cutaneous leishmaniasis (CL) or visceral
      leishmaniasis (VL) were evaluated for their susceptibility to nitric oxide (NO),
      antimony and miltefosine. In a self-healing CL strain of Leishmania major
      (5ASKH), susceptibility to NO and antimony was higher than other species.
      Likewise, a Leishmania amazonensis strain, M2269, showed greater susceptibility
      to NO and antimony than other species but no such correlation was observed with
      miltefosine. Additionally, 5ASKH and M2269 showed poorer free radical scavenging
      capacity as also their thiol levels were lower than species causing VL.
      Collectively, our study suggests that self-healing isolates tend to be more
      susceptible to oxidative stress.

PMID- 22385213
TI  - Automated Retinal Imaging System (ARIS) compared with ETDRS protocol color
      stereoscopic retinal photography to assess level of diabetic retinopathy.
AB  - BACKGROUND: Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard
      field color stereoscopic retinal photography (ETDRS photos) has been a gold
      standard for determining diabetic retinopathy (DR) severity. The Automated
      Retinal Imaging System (ARISTM, model 110, Visual Pathways, Inc., Prescott, AZ)
      acquires seven-sequential color stereoscopic digital images (ARIS images) by a
      semiautomated technician-run process generally corresponding to ETDRS photos. We
      assessed the correlation between a single semiautomated ARIS imaging session
      without any re-imaging and ETDRS photos performed by a certified photographer for
      the determination of DR severity. METHODS: Two independent masked readers graded
      mydriatic ARIS images and ETDRS photos. A third masked retinal specialist
      adjudicated discrepancies. Correlation between the two modalities was compared
      using weighted-kappa statistics. RESULTS: We evaluated 211 eyes of 106 patients
      with varying levels of DR. Partially ungradable images were present in 3.4% of
      ETDRS photos versus 31.8% of ARIS images. Exact agreement and agreement within
      one level between ETDRS photos and ARIS images using only completely gradable
      image sets occurred in 69% (kappa=0.81) and 90% of cases, respectively. Exact
      agreement for clinically significant macular edema was 92.1% (kappa=0.59). There
      was 100% agreement for eyes with high-risk proliferative DR. Within one level of
      DR severity, 100% agreement occurred for the following: questionable
      nonproliferative DR (NPDR), moderate NPDR, and severe NPDR. CONCLUSIONS: Results
      suggest that semiautomated ARIS images compare favorably with ETDRS photos when
      full image sets can be obtained; however, partially ungradable image sets
      occurred almost 10 times more frequently with ARIS images than with ETDRS photos.
      In the two-thirds of cases where ARIS images can be utilized, ARIS can obtain
      retinal images comparable to ETDRS photos while requiring less highly trained
      personnel than generally needed for standard ETDRS photos.

PMID- 22385214
TI  - Gold nanoparticle-enhanced and size-dependent generation of reactive oxygen
      species from protoporphyrin IX.
AB  - Photosensitizer, protoporphyrin IX (PpIX), was conjugated with Au nanoparticles
      (Au NPs) of 19, 66, and 106 nm diameter to study the size-dependent enhancement
      of reactive oxygen species (ROS) formation enabled by Au NPs. The ROS enhancement
      ratio is determined to be 1:2.56:4.72 in order of increasing Au NP size, in
      general agreement with theoretically calculated field enhancement to the fourth
      power. The convergence of the experimental and simulated results suggests that Au
      NP-enhanced and size-dependent ROS formation can be attributed directly to the
      localized electromagnetic field as a result of surface plasmonic resonance of Au
      NPs under light irradiation. In vitro study on the ROS formation enabled by PpIX
      conjugated Au NPs in human breast cancer cells (MDA-MB-231) revealed the similar
      size-dependent enhancement of intracellular ROS formation, while the enhancement
      greatly depended on cellular uptake of Au NPs. Cellular photodynamic therapy
      revealed that cell destruction significantly increased in the presence of Au NPs.
      Compared to the untreated control (0% destruction), 22.6% cell destruction was
      seen in the PpIX alone group and more than 50% cell destruction was obtained for
      all PpIX-conjugated Au NPs. The 66 nm Au NPs yielded the highest cell
      destruction, consistent with the highest cellular uptake and highest ROS
      formation. Clearly, the complex cellular environment, size-dependent cellular
      uptake of Au NPs, and ROS generations are vital contributors to the overall
      cellular PDT efficacy.

PMID- 22385216
TI  - Production of bacillomycin- and macrolactin-type antibiotics by Bacillus
      amyloliquefaciens NJN-6 for suppressing soilborne plant pathogens.
AB  - Bacillus amyloliquefaciens  strains have been used as biocontrol agents for the
      suppression of several soilborne plant pathogens. A clearer understanding of the
      antagonistic mechanisms of action of these bacteria will facilitate their use in
      the control of plant diseases. Antagonistic substances were isolated from the
      fermentation broth of  B. amyloliquefaciens  strain NJN-6 cultures. These
      compounds were preconcentrated using an XAD-16 column and were purified using
      reversed-phase high-performance liquid chromatography (RP-HPLC). Fractions were
      collected from the column and were analyzed, and two homologues of bacillomycin D
      [molecular weights of 1030 Da (C14) and 1044 Da (C15)] and three homologues of
      members of the macrolactin family, macrolactin A, 7-O-malonyl macrolactin A, and
      7-O-succinyl macrolactin A (molecular weights of 402, 487, and 502 Da,
      respectively) were identified using HPLC/electrospray ionization mass
      spectrometry (ESI-MS) analysis. An antagonistic assay showed that bacillomycin D
      and macrolactin exhibited significant antagonistic effects against  Fusarium
      oxysporum  and  Ralstonia solanacearum , respectively. A reliable method for the
      isolation and purification of bacillomycin D and macrolactin from bacterial broth
      cultures was developed. These data will help elucidate the mechanisms that  B.
      amyloliquefaciens  NJN-6 uses for the biocontrol of soilborne plant pathogens.

PMID- 22385215
TI  - Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but
      not lactate correlates positively with Ca2+ signalling in cultured mouse
      glutamatergic neurons.
AB  - We have previously investigated the relative roles of extracellular glucose and
      lactate as fuels for glutamatergic neurons during synaptic activity. The
      conclusion from these studies was that cultured glutamatergic neurons utilize
      glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic
      activity and that lactate alone is not able to support neurotransmitter glutamate
      homoeostasis. Subsequently, a model was proposed to explain these results at the
      cellular level. In brief, the intermittent rises in intracellular Ca2+ during
      activation cause influx of Ca2+ into the mitochondrial matrix thus activating the
      tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of
      the MASH (malate-aspartate shuttle), which in turn will result in anaerobic
      glycolysis and lactate production rather than lactate utilization. In the present
      work, we have investigated the effect of an ionomycin-induced increase in
      intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy
      metabolism employing 13C-labelled glucose and lactate and subsequent mass
      spectrometric analysis of labelling in glutamate, alanine and lactate. The
      results demonstrate that glucose utilization is positively correlated with
      intracellular Ca2+ whereas lactate utilization is not. This result lends further
      support for a significant role of glucose in neuronal bioenergetics and that Ca2+
      signalling may control the switch between glucose and lactate utilization during
      synaptic activity. Based on the results, we propose a compartmentalized CiMASH
      (Ca2+-induced limitation of the MASH) model that includes intracellular
      compartmentation of glucose and lactate metabolism. We define pre- and post
      synaptic compartments metabolizing glucose and glucose plus lactate respectively
      in which the latter displays a positive correlation between oxidative metabolism
      of glucose and Ca2+ signalling.

PMID- 22385217
TI  - Adsorption of sulfite oxidase on self-assembled monolayers from molecular
      dynamics simulations.
AB  - Sulfite oxidase (SO) is an enzyme catalyzing the terminal step of the metabolism
      of sulfur-containing amino acids that is essential for almost all living
      organisms. The catalytic activity of SO in vertebrates strongly depends on the
      efficiency of the intramolecular electron transfer (IET) between the catalytic
      Moco domain and the cytochrome b5 (cyt b5) domain. The IET process is assumed to
      be mediated by large domain motions of the cyt b5 domains within the enzyme.
      Thus, the interaction of SO with charged surfaces may affect the mobility of the
      cyt b5 domain required for IET and consequently hinder SO activation. In this
      study, we present a molecular dynamics approach to investigating the ionic
      strength dependence of the initial surface adsorption of SO in two different
      conformations-the crystallographic structure and the model structure for an
      activated SO-onto mixed amino- and hydroxyl-terminated SAMs. The results show for
      both conformations at low ionic strengths a strong adsorption of the cyt b5 units
      onto the SAM, which inhibits the domain motion event required for IET. Under
      higher ion concentrations, however, the interaction with the surface is weakened
      by the negatively charged ions acting as a buffer and competing in adsorption
      with the cathodic cyt b5 domains. This competition prevents the immobilization of
      the cytochrome b5 units onto the surface, allowing the intramolecular domain
      motions favoring IET. Our predictions support the interpretation of recent
      experimental spectroelectrochemical studies on SO.

PMID- 22385218
TI  - Effects of oxidative stress on amyloid precursor protein processing in rat and
      human platelets.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative illness affecting
      the elderly and is characterized by beta-amyloid (Abeta) deposition in the brain
      (plaques) and in microvessels (Abeta-angiopathy). The reasons for Abeta
      deposition are not clear, but an impaired clearance of Abeta at the blood-brain
      barrier may be implicated and oxidative stress possibly plays a major role in
      this process. Platelets are of particular interest, because they contain high
      levels of the amyloid precursor protein (APP) and in AD an abnormal expression of
      platelets APP fragments was found. The aim of the present study was to
      investigate (1) if oxidative stress induced by hydrogen peroxide (H(2)O(2))
      affects APP expression in rat and human platelets and (2) to compare the APP
      changes with platelets of AD patients. In rat platelets, all three fragments of
      APP (130-110-106 kilo Dalton, kDa) were found. H(2)O(2) (10 mM, 20 minutes)
      significantly reduced all three fragments in rat platelets, did not affect CD62P
      staining and slightly increased the size of actin as seen in the Western blot.
      The effect was not seen at 1 mM H(2)O(2) and was counteracted by glutathione.
      Immunohistochemistry for CD62P, CD61, APP and Annexin-V was used to verify the
      changes at the cellular level. In platelets of young volunteers (age = 33 +/- 4
      years), 10 mM H(2)O(2) markedly reduced the smaller APP 110 and 106 kDa fragments
      after 20 minutes. Our data show that platelets of AD patients (age = 80 +/- 1
      years) had a significant reduced 130 kDa fragment compared to controls (age = 70
      +/- 2 years). In summary, oxidative stress may account for a dysfunctional
      processing of APP in rat and human control platelets and possibly in AD patients.

PMID- 22385219
TI  - Inhibition of platelet aggregation by prostaglandin E1 (PGE1) in diabetic
      patients during therapy with clopidogrel and aspirin.
AB  - Diabetes mellitus (DM) is associated with increased platelet activation and
      reduced platelet inhibition by clopidogrel. Prostaglandin E1 (PGE1) stimulates
      adenyl cyclase activity in platelets and increases cyclic AMP concentrations,
      which inhibit Ca(2+)release and platelet aggregation induced by P2Y1 receptor
      activation. PGE1 is included in the VerifyNow P2Y12 assay to suppress P2Y1
      induced platelet aggregation. We hypothesized that diabetes mellitus may be
      associated with altered response to PGE1 in subjects treated with clopidogrel.
      Subjects with established coronary artery disease who were taking clopidogrel 75
      mg daily and aspirin for >14 days were enrolled (n = 96). Diabetic (n = 34) were
      compared with non-diabetic subjects (n = 62). VerifyNow P2Y12 assay and light
      transmittance aggregometry (LTA) were performed using ADP as agonist with and
      without addition of PGE1. Genomic DNA was genotyped for common cytochrome P450
      (CYP) 2C19 variants using Taqman assays. Residual on-treatment platelet
      aggregation induced by 20 uM ADP was not significantly different between subjects
      with and without DM. Addition of 22 nM and 88 nM PGE1 to 20 uM ADP resulted in a
      significant reduction of maximal platelet aggregation (MPA). Residual LTA
      platelet aggregation with PGE1 and VerifyNow P2Y12 platelet reactivity were
      significantly higher in subjects with DM than those without DM and in carriers of
      CYP 2C19*2 polymorphism. We conclude that an impaired inhibitory response to PGE1
      may contribute to the high platelet reactivity phenotype in subjects with DM
      treated with clopidogrel. Addition of PGE1 to ADP agonist platelet assays may
      identify subjects with blunted inhibitory response to prostaglandins and result
      in a higher proportion of subjects with DM being classified as non-responders.

PMID- 22385220
TI  - Successful treatment of right-sided native valve methicillin-resistant
      Staphylococcus aureus endocarditis and septicaemia with teicoplanin and
      rifampicin: a case report.
AB  - Vancomycin is the drug of choice in the treatment of methicillin-resistant
      Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical
      complications like renal failure alters vancomycin pharmacokinetics, leading to
      drug accumulation and toxicity. This highlights the need to identify an effective
      substitute for treating MRSA infections when vancomycin cannot be used. We report
      the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis
      with septicaemia and a right upper lobe cavity caused by MRSA. The patient also
      presented with renal failure, which precluded the use of vancomycin for
      treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and
      the infection was successfully treated. This case report provides evidence of the
      effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia
      in situations where the use of vancomycin is contraindicated.

PMID- 22385221
TI  - Metal-cation-based anion exchange membranes.
AB  - Here we present the first metal-cation-based anion exchange membranes (AEMs),
      which were synthesized by copolymerization and cross-linking of a norbornene
      monomer functionalized with a water-soluble bis(terpyridine)ruthenium(II) complex
      and dicyclopentadiene. Each ruthenium complex has two associated counteranions,
      unlike most ammonium- and phosphonium-based membranes with single cation-anion
      pairs. The resulting AEMs show anion conductivities and mechanical properties
      comparable to those of traditional quaternary-ammonium-based AEMs as well as good
      alkaline stability and methanol tolerance. These results suggest that metal
      cation-based polymers hold promise as a new class of materials for anion
      conducting applications.

PMID- 22385222
TI  - Commentary: earlobe keloids: classification by gross morphology determines proper
      surgical approach.

PMID- 22385223
TI  - Commentary: are all fractional resurfacing devices equal with regard to induction
      of fibrosis?

PMID- 22385224
TI  - Commentary: electromagnetic radiation and wound healing.

PMID- 22385225
TI  - Blunt needles (microcannulae) for infiltrating local anesthetics.

PMID- 22385226
TI  - RE: micropunch technique.

PMID- 22385227
TI  - Treatment of metophyma with the carbon dioxide laser.

PMID- 22385228
TI  - Diagnostic pacing maneuvers for supraventricular tachycardias: part 2.
AB  - The approach to supraventricular tachycardia (SVT) diagnosis can be complex
      because it involves synthesizing baseline electrophysiologic features, features
      of the SVT, and the response(s) to pacing maneuvers. In this two-part review, we
      will mainly explore the latter while recognizing that neither of the former can
      be ignored, for they provide the context in which diagnostic pacing maneuvers
      must be correctly chosen and interpreted. Part 1 involved a detailed
      consideration of ventricular overdrive pacing, since this pacing maneuver
      provides the diagnosis in the majority of cases. In Part 2, other diagnostic
      pacing maneuvers that might be helpful when ventricular overdrive pacing is not
      diagnostic or appropriate, including attempts to reset SVT with single atrial or
      ventricular beats, para-Hisian pacing, apex versus base pacing, and atrial
      overdrive pacing, are discussed, as are some specific diagnostic SVT challenges
      encountered in the electrophysiology lab. There is considerable literature on
      this topic, and this review is by no means meant to be all-encompassing. Rather,
      we hope to clearly explain and illustrate the physiology, strengths, and
      weaknesses of what we consider to be the most important and commonly employed
      diagnostic pacing maneuvers, that is, those that trainees in cardiac
      electrophysiology should be well familiar with at a minimum.

PMID- 22385229
TI  - Renal Fanconi syndrome as a cause of chronic kidney disease in patients with
      monoclonal gammopathy of undetermined significance: partially reversed renal
      function by high-dose dexamethasone with bortezomib.

PMID- 22385230
TI  - Viruses and type 1 diabetes: ignorance acquires a better vocabulary.
AB  - The hypothesis that a virus might in some way be involved in the causation of
      type 1 diabetes has a long history, but decades of research have failed to
      resolve the issue beyond reasonable doubt. Viruses could potentially play a
      primary role in the pathogenesis of type 1 diabetes by initiating autoimmunity, a
      secondary role by promoting established immune responses, or a tertiary role by
      precipitating the onset of hyperglycaemia. There is currently little evidence to
      suggest that viruses play a primary role in the causation of type 1 diabetes, let
      alone a necessary or sufficient role. Secondary or tertiary roles remain
      possible, but have yet to be confirmed in prospective studies.

PMID- 22385231
TI  - Immunology in the clinic review series: focus on type 1 diabetes and viruses: the
      role of viruses in type 1 diabetes: a difficult dilemma.
AB  - Convincing evidence now indicates that viruses are associated with type 1
      diabetes (T1D) development and progression. Human enteroviruses (HEV) have
      emerged as prime suspects, based on detection frequencies around clinical onset
      in patients and their ability to rapidly hyperglycaemia trigger in the non-obese
      diabetic (NOD) mouse. Whether or not HEV can truly cause islet autoimmunity or,
      rather, act by accelerating ongoing insulitis remains a matter of debate. In view
      of the disease's globally rising incidence it is hypothesized that improved
      hygiene standards may reduce the immune system's ability to appropriately respond
      to viral infections. Arguments in favour of and against viral infections as major
      aetiological factors in T1D will be discussed in conjunction with potential
      pathological scenarios. More profound insights into the intricate relationship
      between viruses and their autoimmunity-prone host may lead ultimately to
      opportunities for early intervention through immune modulation or vaccination.

PMID- 22385232
TI  - Immunology in the clinic review series; focus on type 1 diabetes and viruses: the
      enterovirus link to type 1 diabetes: critical review of human studies.
AB  - The hypothesis that under some circumstances enteroviral infections can lead to
      type 1 diabetes (T1D) was proposed several decades ago, based initially on
      evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA
      has been detected more frequently in serum of patients than in control subjects,
      but such studies are susceptible to selection bias and reverse causality. Here,
      we review critically recent evidence from human studies, focusing on longitudinal
      studies with potential to demonstrate temporal association. Among seven
      longitudinal birth cohort studies, the evidence that enterovirus infections
      predict islet autoimmunity is quite inconsistent in our interpretation, due
      partially, perhaps, to heterogeneity in study design and a limited number of
      subjects studied. An association between enterovirus and rapid progression from
      autoimmunity to T1D was reported by one longitudinal study, but although
      consistent with evidence from animal models, this novel observation awaits
      replication. It is possible that a potential association with initiation and/or
      progression of islet autoimmunity can be ascribed to a subgroup of the many
      enterovirus serotypes, but this has still not been investigated properly. There
      is a need for larger studies with frequent sample intervals and collection of
      specimens of sufficient quality and quantity for detailed characterization of
      enterovirus. More research into the molecular epidemiology of enteroviruses and
      enterovirus immunity in human populations is also warranted. Ultimately, this
      knowledge may be used to devise strategies to reduce the risk of T1D in humans.

PMID- 22385233
TI  - Immunology in the clinic review series; focus on type 1 diabetes and viruses: how
      viral infections modulate beta cell function.
AB  - Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease
      characterized by the autoimmune destruction of insulin-producing pancreatic islet
      beta cells in genetically susceptible individuals. Epidemiological evidence has
      also documented the constant rise in the incidence of T1DM worldwide, with viral
      infections representing one of the candidate environmental risk factors
      identified by several independent studies. In fact, epidemiological data showed
      that T1DM incidence increases after epidemics due to enteroviruses and that
      enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time
      of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that
      viruses can infect pancreatic beta cells with consequent effects ranging from
      functional damage to cell death.

PMID- 22385234
TI  - Immunology in the clinic review series; focus on type 1 diabetes and viruses: the
      innate immune response to enteroviruses and its possible role in regulating type
      1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a
      misdirected T cell response to the pancreatic beta cell. In recent years, there
      has been a growing interest in the innate immune system as a regulator of disease
      development. Genome-wide association studies have identified diabetes-associated
      polymorphisms in genes encoding proteins with functions related to the innate
      immune response. Moreover, enteroviruses, known to activate a strong innate
      immune response, have been implicated in the disease pathogenesis. In this
      review, we discuss the innate immune response elicited by enteroviruses and how
      this response may regulate T1D development.

PMID- 22385235
TI  - Immunology in the clinic review series; focus on type 1 diabetes and viruses:
      enterovirus, thymus and type 1 diabetes pathogenesis.
AB  - Thymus dysfunction, especially immune suppression, is frequently associated with
      various virus infections. Whether viruses may disturb the thymus function and
      play a role in the pathogenesis of autoimmune diseases is an open issue.
      Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested
      as potential inducers or aggravating factors of type 1 diabetes (T1D)
      pathogenesis in genetically predisposed individuals. Several pathogenic
      mechanisms of enterovirus-induced T1D have been suggested. One of these
      mechanisms is the impairment of central self-tolerance due to viral infections.
      Coxsackievirus-B4 is able to infect murine thymus in vitro and in vivo and to
      infect human thymus in vitro. Thymic epithelial cells and thymocytes are targets
      of infection with this virus, and several abnormalities, especially disturbance
      of maturation/differentiation processes, were observed. Altogether, these data
      suggest that CV-B infection of thymus may be involved in the pathogenesis of T1D.
      Further investigations are needed to explore this hypothesis.

PMID- 22385236
TI  - Immunology in the clinic review series; focus on type 1 diabetes and viruses:
      role of antibodies enhancing the infection with Coxsackievirus-B in the
      pathogenesis of type 1 diabetes.
AB  - Type 1 diabetes results from an interaction between genetic and environmental
      factors. Coxsackieviruses B (CV-B) are major environmental candidates, as
      suggested by epidemiological and experimental studies. The mechanisms leading to
      the disease involve interactions between the virus, host target tissue (pancreas)
      and the immune system. The infection of target cells with viruses can be
      prevented by antibodies. Conversely, the infection can be enhanced by antibodies.
      The antibody-dependent enhancement (ADE) of infection has been described with
      various viruses, especially Picornaviruses. In mice infected with CV-B3 this
      phenomenon resulted in an extended inflammatory reaction and myocarditis. In the
      human system non-neutralizing antibodies can increase the infection of monocytes
      with CV-B4 and stimulate the production of interferon (IFN)-alpha by these cells
      in vitro. CV-B4/immunoglobulin (Ig)G immune complexes interacted with a specific
      viral receptor [Coxsackievirus and adenovirus receptor (CAR)] and with IgG Fc
      fraction receptors (FcgammaRII and FcgammaRIII) at the surface of monocytes. The
      virus-antibody complexes are internalized (CAR) and receptors for the Fc of IgG
      (FcgammaRII and FcgammaRIII). Such antibodies have been detected in patients with
      type 1 diabetes and they could be responsible for the presence of enteroviral RNA
      and IFN-alpha in peripheral blood mononuclear cells (PBMC) of these individuals.
      The target of enhancing antibodies has been identified as the VP4 protein, which
      allowed the detection of these antibodies by enzyme-linked immunosorbent assay
      (ELISA). It cannot be excluded that antibodies enhancing the infection with CV-B
      may play a role in the pathogenesis of type 1 diabetes, induced or aggravated by
      these viruses. They can cause a viral escape from the immune response and may
      participate in the spreading of viruses to beta cells. Whether enhancing
      antibodies raised against VP4 can play a role in iterative homologous and/or
      heterologous CV-B infections and in the persistence of viruses within the host
      deserves further study.

PMID- 22385237
TI  - Cell death pathways and autophagy in the central nervous system and its
      involvement in neurodegeneration, immunity and central nervous system infection:
      to die or not to die--that is the question.
AB  - Death rules our lives. In this short paper, we summarize new insights into
      molecular mechanisms of neurodegeneration. Here we review the most important
      processes of cell death: apoptosis and oncosis. We focus on autophagy, which is
      pivotal for neuronal homeostasis, in the context of neurodegeneration, infection
      and immunity. Its dysfunction has been linked to several neurodegenerative
      diseases such as Parkinson's, Huntington's and Alzheimer's diseases. Our
      understanding is still incomplete, but may highlight attractive new avenues for
      the development of treatment strategies to combat neurodegenerative diseases.

PMID- 22385238
TI  - Classification of primary immunodeficiency diseases by the International Union of
      Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiency 2011.

PMID- 22385239
TI  - Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies
      are associated with different immunoregulatory milieu in newly diagnosed type 1
      diabetes patients.
AB  - Several studies correlated genetic background and pancreatic islet-cell
      autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but
      there are no data evaluating the relationship among these markers with serum
      cytokines, regulatory T cells and beta cell function. This characterization has a
      potential importance with regard to T1AD patients' stratification and follow-up
      in therapeutic prevention. In this study we showed that peripheral sera cytokines
      [interleukin (IL)-12, IL-6, II-1beta, tumour necrosis factor (TNF)-alpha, IL-10]
      and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in
      newly diagnosed T1AD patients when compared to healthy controls (P < 0.001).
      Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0.80; P
      = 0.000), IL-8 and TNF-alpha (r = 0.60; P = 0.000); IL-8 and IL-12 (r = 0.57; P =
      0.001) and TNF-alpha and IL-12 (r = 0.93; P = 0.000). Glutamic acid decarboxylase
      65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = 
      0.45; P = 0.011) and CCL2 (r = -0.65; P = 0.000), while IA-2A showed a negative
      correlation with IL-10 (r = -0.38; P = 0.027). Human leucocyte antigen (HLA) DR3,
      DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with
      pancreatic islet cell antibodies or cytokines studied. In summary, our results
      revealed that T1AD have a proinflammatory cytokine profile compared to healthy
      controls and that IA-2A sera titres seem to be associated with a more
      inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of
      these data in the pre-T1AD phase could help to explain the mechanistic of the
      well-known role of IA-2A as a more specific marker of beta-cell damage than GADA
      during the natural history of T1AD.

PMID- 22385240
TI  - Excessive CD4+ T cells co-expressing interleukin-17 and interferon-gamma in
      patients with Behcet's disease.
AB  - Excessive T helper type 1 (Th1) cell activity has been reported in Behcet's
      disease (BD). Recently, association of Th17 cells with certain autoimmune
      diseases was reported, and we thus investigated circulating Th17 cells in BD.
      CD4(+) CD45RO(-)  (naive) T cells were cultured with Th0-, Th1-, Th2- and Th17
      related cytokines and antibodies, and their mRNA was studied by real-time
      polymerase chain reaction (PCR). When naive CD4(+)  T cells were cultured with
      Th1- and Th17-related cytokines, interferon (IFN)-gamma mRNA and interleukin (IL)
      17 mRNA were up-regulated, respectively, in BD patients. Naive CD4(+)  T cells
      cultured in a Th17 cell-inducing condition expressed IL-23 receptor (IL-23R) mRNA
      excessively. IL-17 mRNA expression was induced only when naive CD4(+) T cells
      were cultured in the presence of IL-23. CD4(+)  T cells cultured with Th17
      cytokines expressed excessive RAR-related orphan receptor C (RORC) mRNA. Using
      intracellular cytokine staining, we found that CD45RO(+) (memory) CD4(+)  T cells
      producing IL-17 and IFN-gamma simultaneously were increased significantly. Memory
      CD4(+)  T cells producing IFN-gamma but not IL-17 decreased profoundly in BD
      patients. CD4(+)  T cells producing IL-17 and IFN-gamma simultaneously were found
      in BD skin lesions. Collectively, we found excessive CD4(+)  T cells producing IL
      17 and IFN-gamma (Th1/Th17) cells in patients with BD, and possible involvement
      of IL-23/IL-23R pathway for the appearance of excessive Th1/Th17 cells.

PMID- 22385241
TI  - Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis
      patients?
AB  - Plasma exchange is used increasingly as an individual therapeutic decision for
      treating of severe, steroid-resistant relapses of multiple sclerosis (MS).
      However, given that its mechanism of action in this CD4(+)  T cell-mediated
      autoimmune disease remains unknown, it is not yet considered as a routine therapy
      for this prevalent neuroimmune disorder. In this regard, we hypothesized that
      plasma exchange, by depleting the body of inflammatory mediators that acts as
      providers of co-stimulatory signals for the adaptive immune system, provides the
      immune system with an exceptional break for de-novo recognition of autoantigens
      in a tolerogenic manner. This may lead to an increase in the frequency and
      function of myelin-specific regulatory T cells. For evaluating this we suggest
      some in vitro and in vivo studies to analyse the effects of varied dilutions of
      normal and MS plasmas on the induction of regulatory T cells or on the function
      of isolated and purified regulatory T cells. Clarifying the effects of
      therapeutic plasma exchange on regulatory T cells as the major controllers of
      autoimmune responses may provide us with strong evidence to use this procedure as
      a disease-modifying treatment in remission phase for reducing the rate and
      severity of future attacks, in addition to more trustworthy therapy in severe
      relapses of MS.

PMID- 22385242
TI  - Combination of nifedipine and subtherapeutic dose of cyclosporin additively
      suppresses mononuclear cells activation of patients with rheumatoid arthritis and
      normal individuals via Ca(2+) -calcineurin-nuclear factor of activated T cells
      pathway.
AB  - Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of
      rheumatoid arthritis (RA). However, the potential implication of calcium channel
      blocker in RA remained unknown. We hypothesized that nifedipine, an L-type
      calcium channel blocker, combined with a calcineurin inhibitor, could suppress T
      cell activation via targeting different level of the Ca(2+)  signalling pathway.
      The percentage of activated T cells and the apoptotic rate of mononuclear cells
      (MNCs) was measured by flow cytometry. The MNC viability, cytokine production,
      cytosolic Ca(2+)  level and activity of the nuclear factor of activated T cells
      (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT
      regulated gene expression, including interleukin (IL)-2, interferon (IFN)-gamma
      and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by
      real-time polymerase chain reaction (PCR). We found that the percentage of
      activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA
      patients. High doses of nifedipine (50 uM) increased MNCs apoptosis, inhibited T
      cell activation and decreased T helper type 2 (Th1) (IFN-gamma)/Th2 (IL-10)
      cytokine production in both groups. The Ca(2+)  influx was lower in anti-CD3 +
      anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed
      by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of
      cyclosporin, 1 uM nifedipine suppressed the percentage of activated T cells in
      both groups. Moreover, this combination suppressed more IFN-gamma secretion and
      NFAT-regulated gene (GM-CSF and IFN-gamma) expression in RA-MNCs than normal MNCs
      via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+)
      channel blockers and subtherapeutic doses of cyclosporin act additively to
      suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition
      of T cell activity. We propose that this combination may become a potential
      treatment of RA.

PMID- 22385243
TI  - Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards
      CD28 engagement.
AB  - Human lamina propria T lymphocytes (LPT) possess functional properties profoundly
      different from those of peripheral blood T lymphocytes (PBT). While they are
      characterized by a low proliferative response to T cell receptor (TCR)/CD3
      stimulation in vitro their responsiveness to activation through the 'co
      stimulatory' CD2-receptor is enhanced when compared to PBT. In this study, we
      demonstrate that engagement of another co-stimulatory receptor on both LPT and
      PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly
      activates the former but not the latter through a PI3-kinase dependent signalling
      pathway leading to the production of inflammatory cytokines such as interleukin
      (IL)-2, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and
      granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition to the
      high sensitivity of LPT to CD2 stimulation, this finding supports the notion that
      'non-specific/innate' mechanisms to activate T lymphocytes play a predominant
      role vis-a-vis'TCR driven/adaptive' responses in the intestinal mucosa.
      Furthermore, it suggests that results from preclinical tests for therapeutic
      antibodies performed with human blood derived T cells are probably insufficient
      to predict reactivities of tissue-resident immune cells, which--given their
      quantitative predominance--may critically determine the in-vivo response to such
      compounds.

PMID- 22385244
TI  - Transglutaminase 2 expression is enhanced synergistically by interferon-gamma and
      tumour necrosis factor-alpha in human small intestine.
AB  - Transglutaminase 2 (TG2) is expressed ubiquitously, has multiple physiological
      functions and has also been associated with inflammatory diseases,
      neurodegenerative disorders, autoimmunity and cancer. In particular, TG2 is
      expressed in small intestine mucosa where it is up-regulated in active coeliac
      disease (CD). The aim of this work was to investigate the induction of TG2
      expression by proinflammatory cytokines [interleukin (IL)-1, IL-6, tumour
      necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-15] and the signalling
      pathways involved, in human epithelial and monocytic cells and in intestinal
      tissue from controls and untreated CD patients. Here we report that IFN-gamma was
      the most potent inducer of TG2 expression in the small intestinal mucosa and in
      four [Caco-2, HT-29, Calu-6 and human acute monocytic leukaemia cell line (THP
      1)] of five cell lines tested. The combination of TNF-alpha and IFN-gamma
      produced a strong synergistic effect. The use of selective inhibitors of
      signalling pathways revealed that induction of TG2 by IFN-gamma was mediated by
      phosphoinositide 3-kinase (PI3K), while c-Jun N-terminal kinase (JNK) and p38
      mitogen-activated protein kinase (MAPK) were required for TNF-alpha activation.
      Quantitative polymerase chain reaction (PCR), flow cytometry and Western blot
      analysis showed that TG2 expression was blocked completely when stimulation by
      either TNF-alpha or IFN-gamma was performed in the presence of nuclear factor
      (NF)-kappaB inhibitors (sulphasalazine and BAY-117082). TG2 was up-regulated
      substantially by TNF-alpha and IFN-gamma in intestinal mucosa in untreated CD
      compared with controls. This study shows that IFN-gamma, a dominant cytokine in
      intestinal mucosa in active CD, is the most potent inducer of TG2, and synergism
      with TNF-alpha may contribute to exacerbate the pathogenic mechanism of CD.
      Selective inhibition of signalling pathways may be of therapeutic benefit.

PMID- 22385245
TI  - In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in
      human neutrophils.
AB  - In order to address neutrophil activation during inflammation we assessed the
      expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo
      extravasation. Extravasated neutrophils were collected from 11 healthy study
      subjects by a skin chamber technique and compared to neutrophils in peripheral
      blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase
      chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent
      assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following
      extravasation, demonstrated by both gene array and qPCR. Western blot
      demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This
      was confirmed further in neutrophils by flow cytometry and iEM that also
      demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by
      N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral
      neutrophils with IL-1 resulted in transcription of NFkappaB and a number of
      downstream chemokines and the corresponding chemokines were also induced
      following in-vivo extravasation. The present results demonstrate that IL-1R1 is
      induced following extravasation and exists on the neutrophil surface, as well as
      in a mobile intracellular pool. Furthermore, neutrophils express functional IL
      1R1 as demonstrated by the induction of chemokines following IL-1 stimulation.
      The results indicate a potential role for IL-1 in the activation of neutrophils
      at inflammatory sites.

PMID- 22385246
TI  - Mechanical stress-activated immune response genes via Sirtuin 1 expression in
      human periodontal ligament cells.
AB  - Recently, Sirtuin 1 (SIRT1) has been implicated in the molecular control of
      ageing and immune response. Although the remodelling of periodontal ligament
      (PDL) in response to mechanical stress (MS) is mediated by several host factors,
      including cytokines and chemokines, the transmission of mechanical stimuli into
      specific cellular activity is still not understood fully. This study aimed to
      investigate the effects of MS, particularly cyclic strain, on immune response
      genes, as well as SIRT1 and its signal transduction pathways, in human PDL cells.
      MS up-regulated the expression of SIRT1 and immune response genes encoding
      cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta],
      chemokines [IL-8, monocyte cheoattractant protein (CCL)-20], defensins [human
      beta-defensin (hBD)-2, hBD-3] and Toll-like receptors (TLR-2 and TLR-4) in a
      force- and time-dependent manner. The SIRT1 inducers resveratrol and
      isonicotinamide attenuated MS-induced cytokine and chemokine expression, but
      enhanced the expression of defensins and TLRs. Blockade of SIRT1 activity by the
      SIRT1 inhibitors sirtinol and nicotinamide and down-regulation of SIRT1
      expression by SIRT1 siRNA reduced the stimulatory effects of MS on defensins and
      TLRs, but increased its effects on cytokines and chemokines. MS induced
      activation of protein kinase B (Akt), protein kinase C (PKC), nuclear factor (NF)
      kappaB and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK). Treatment with the anti
      oxidants N-acetylcysteine and glutathione inhibited MS-induced reactive oxygen
      species production and expression of cytokines, chemokines, defensins and TLRs.
      These results suggest that MS activates human PDL cells to express immune/defence
      genes encoding cytokines, chemokines, defensins and TLRs via a SIRT1 pathway.

PMID- 22385247
TI  - Sevoflurane reduces severity of acute lung injury possibly by impairing formation
      of alveolar oedema.
AB  - Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various
      degrees of water and proteins. Physiologically, sodium enters through apical
      sodium channels (ENaC) and is extruded basolaterally by a sodium-potassium
      adenosine-triphosphatase pump (Na(+) /K(+) -ATPase). Water follows to maintain
      iso-osmolar conditions and to keep alveoli dry. We postulated that the volatile
      anaesthetic sevoflurane would impact oedema resolution positively in an in-vitro
      and in-vivo model of ALI. Alveolar epithelial type II cells (AECII) and mixed
      alveolar epithelial cells (mAEC) were stimulated with 20 ug/ml lipopolysaccharide
      (LPS) and co-exposed to sevoflurane for 8 h. In-vitro active sodium transport via
      ENaC and Na(+) /K(+) -ATPase was determined, assessing (22) sodium and (86)
      rubidium influx, respectively. Intratracheally applied LPS (150 ug) was used for
      the ALI in rats under sevoflurane or propofol anaesthesia (8 h). Oxygenation
      index (PaO(2) /FiO(2) ) was calculated and lung oedema assessed determining lung
      wet/dry ratio. In AECII LPS decreased activity of ENaC and Na(+) /K(+) -ATPase by
      17.4% +/- 13.3% standard deviation and 16.2% +/- 13.1%, respectively. These
      effects were reversible in the presence of sevoflurane. Significant better
      oxygenation was observed with an increase of PaO(2) /FiO(2)  from 189 +/- 142
      mmHg to 454 +/- 25 mmHg after 8 h in the sevoflurane/LPS compared to the
      propofol/LPS group. The wet/dry ratio in sevoflurane/LPS was reduced by 21.6% +/-
      2.3% in comparison to propofol/LPS-treated animals. Sevoflurane has a stimulating
      effect on ENaC and Na(+) /K(+) -ATPase in vitro in LPS-injured AECII. In-vivo
      experiments, however, give strong evidence that sevoflurane does not affect water
      reabsorption and oedema resolution, but possibly oedema formation.

PMID- 22385248
TI  - Immunoglobulin G subclass levels and antibody responses to the 2009 influenza A
      (H1N1) monovalent vaccine among human immunodeficiency virus (HIV)-infected and
      HIV-uninfected adults.
AB  - Immunoglobulin (Ig)G levels are important for antibody vaccine responses and IgG
      subclass deficiencies have been associated with severe 2009 influenza A (H1N1)
      infections. Studies have demonstrated variations in immune responses to the H1N1
      vaccine, but the aetiology of this is unknown. We determined the associations
      between pre-vaccination overall and influenza-specific IgG subclass levels and
      2009 H1N1-specific antibody responses post-vaccination (robust versus poor at day
      28) stratified by human immunodeficiency virus (HIV) status. Logistic regression
      models were utilized to evaluate whether pre-vaccination IgG subclass levels were
      associated with the antibody response generated post-vaccination. We evaluated 48
      participants as part of a clinical study who were stratified by robust versus
      poor post-vaccination immune responses. Participants had a median age of 35
      years; 92% were male and 44% were Caucasian. HIV-infected adults had a median CD4
      count of 669 cells/mm(3) , and 79% were receiving highly active anti-retroviral
      therapy. HIV-infected participants were more likely to have IgG2 deficiency (<240
      mg/dl) than HIV-uninfected individuals (62% versus 4%, P < 0.001). No association
      of pre-vaccination IgG subclass levels (total or influenza-specific) and the
      antibody response generated by HIN1 vaccination in either group was found. In
      summary, pre-vaccination IgG subclass levels did not correlate with the ability
      to develop robust antibody responses to the 2009 influenza A (H1N1) monovalent
      vaccine. IgG2 deficiencies were common among HIV-infected individuals but did not
      correlate with poor influenza vaccine responses. Further investigations into the
      aetiology of disparate vaccine responses are needed.

PMID- 22385249
TI  - Control of Mycobacterium tuberculosis growth by activated natural killer cells.
AB  - We characterized the underlying mechanisms by which glutathione (GSH)-enhanced
      natural killer (NK) cells inhibit the growth of Mycobacterium tuberculosis (M.
      tb) inside human monocytes. We observed that in healthy individuals, treatment of
      NK cells with N-acetyl cysteine (NAC), a GSH prodrug in conjunction with
      cytokines such as interleukin (IL)-2 + IL-12, resulted in enhanced expression of
      NK cytotoxic ligands (FasL and CD40L) with concomitant stasis in the
      intracellular growth of M. tb. Neutralization of FasL and CD40L in IL-2 + IL-12 +
      NAC-treated NK cells resulted in abrogation in the growth inhibition of M. tb
      inside monocytes. Importantly, we observed that the levels of GSH are decreased
      significantly in NK cells derived from individuals with HIV infection compared to
      healthy subjects, and this decrease correlated with a several-fold increase in
      the growth of M. tb inside monocytes. This study describes a novel innate defence
      mechanism adopted by NK cells to control M. tb infection.

PMID- 22385251
TI  - How should we manage multiple skin ulcers associated with calciphylaxis?

PMID- 22385250
TI  - Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular
      traps formation leading to a more efficient bacterial clearance in mice.
AB  - Tolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a
      primary contact with LPS results in a minimal response when a second exposure
      with the same stimulus occurs. However, active important defence mechanisms are
      mounted during the tolerant state. Our aim was to assess the contribution of
      polymorphonuclear neutrophils (PMN) in the clearance of bacterial infection in a
      mouse model of tolerance to LPS. After tolerance was developed, we investigated
      in vivo different mechanisms of bacterial clearance. The elimination of a locally
      induced polymicrobial challenge was more efficient in tolerant mice both in the
      presence or absence of local macrophages. This was related to a higher number of
      PMN migrating to the infectious site as a result of an increased number of PMN
      from the marginal pool with higher chemotactic capacity, not because of
      differences in their phagocytic activity or reactive species production. In vivo,
      neutrophils extracellular trap (NET) destruction by nuclease treatment abolished
      the observed increased clearance in tolerant but not in control mice. In line
      with this finding, in vitro NETs formation was higher in PMN from tolerant
      animals. These results indicate that the higher chemotactic response from an
      increased PMN marginal pool and the NETs enhanced forming capacity are the main
      mechanisms mediating bacterial clearance in tolerant mice. To sum up, far from
      being a lack of response, tolerance to LPS causes PMN priming effects which
      favour distant and local anti-infectious responses.

PMID- 22385252
TI  - Permanent dysphagia in familial amyloid polyneuropathy (ATTRVal30Met).
AB  - Gastrointestinal symptoms are frequent in familial amyloid polyneuropathy, mainly
      resulting from autonomic nervous system involvement. Dysphagia is one of the
      possible symptoms, although rarely severe or sudden. We describe a case of a
      sudden onset and severe dysphagia, a rare form of presentation, in a patient
      whose polyneuropathy was still beeing investigated and turned out to be
      ATTRVal30Met-polyneuropathy.

PMID- 22385253
TI  - Effects of the oncogenic V(664)E mutation on membrane insertion, structure, and
      sequence-dependent interactions of the Neu transmembrane domain in micelles and
      model membranes: an integrated biophysical and simulation study.
AB  - Receptor tyrosine kinases bind ligands such as cytokines, hormones, and growth
      factors and regulate key cellular processes, including cell division. They are
      also implicated in the development of many types of cancer. One such example is
      the Neu receptor tyrosine kinase found in rats (homologous to the human ErbB2
      protein), which can undergo a valine to glutamic acid (V(664)E) mutation at the
      center of its alpha-helical transmembrane domain. This substitution results in
      receptor activation and oncogenesis. The molecular basis of this dramatic change
      in behavior upon introduction of the V(664)E mutation has been difficult to pin
      down, with conflicting results reported in the literature. Here we report the
      first quantitative, thermodynamic analysis of dimerization and biophysical
      characterization of the rat Neu transmembrane domain and several mutants in a
      range of chemical environments. These data have allowed us to identify the
      effects of the V(664)E mutation in the isolated TM domain with respect to protein
      protein and protein-lipid interactions, membrane insertion, and secondary
      structure. We also report the results from a 100 ns atomistic molecular dynamics
      simulation of the Neu transmembrane domain in a model membrane bilayer
      (dipalmitoylphosphatidylcholine). The results from simulation and experiment are
      in close agreement and suggest that, in the model systems investigated, the
      V(664)E mutation leads to a weakening of the TM dimer and a change in sequence
      dependent interactions. These results are contrary to recent results obtained in
      mammalian membranes, and the implications of this are discussed.

PMID- 22385254
TI  - Nanoscale E-cadherin ligand patterns show threshold size for cellular adhesion
      and adherence junction formation.
AB  - The role of ligand spatial distribution on the formation of cadherin mediated
      cell-cell contacts is studied utilizing nanopatterns of E-cadherin ligands.
      Protein patches ranging in size from 100 to 800 nm prepared by colloidal
      lithography critically influence adhesion, spreading, and formation of adherence
      junctions in epithelial cells. Cells at 100 nm patterns show poor adhesion, while
      larger pattern sizes show good adhesion, significant spreading, and defined
      cortical actin. We estimate a threshold of 0.03 MUm(2) for epithelial cellular
      attachment via E-Cadherin.

PMID- 22385255
TI  - Extrapolation of an empirical elbow muscle co-activation relationship to a novel
      task set: implications for predictions of individual muscle demands.
AB  - Biomechanical optimisation models applying efficiency-based objective functions
      often underestimate antagonist contributions. Previous work has quantified an
      empirical co-activation relationship in the elbow musculature, demonstrating that
      implementing this relationship as a constraint in an elbow muscle force
      prediction model improves muscle force predictions. The current study evaluated
      this modified model by extrapolating the co-activation relationship to 36 novel
      isometric unilateral, right-handed exertions, including those requiring greater
      intensity of effort and performed in different postures. Surface electromyography
      was recorded from the elbow flexors and extensors. Novel extrapolative co
      activation relationships were developed and used as constraints in a muscle force
      prediction model. Model predictions using both constraints were compared with
      empirical biophysical data. Predictions by the modified model were more
      consistent with biophysical data than those by the original model for the novel
      exertions. Novel co-activation relationships did not further enhance predictions
      when compared with the previous relationship, suggesting that extrapolation of
      the previous relationship is feasible. 

PMID- 22385256
TI  - A genetic variant in 3'-untranslated region of cyclooxygenases-2 gene is
      associated with risk of gastric cancer in a Chinese population.
AB  - Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis,
      including inflammation, apoptosis inhibition, immune response suppression, tumor
      cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers,
      including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase
      2 (PTGS2) gene. We hypothesized that potentially functional polymorphisms in
      PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we
      conducted a case-control study with 1681 gastric cancer cases and 1916 control
      subjects in a Chinese population to evaluate the association between a
      polymorphism in 3'-untranslated region of PTGS2, rs5275, and the risk of gastric
      cancer. Logistic regression analysis revealed that variant allele (C) of rs5275
      was significantly associated with an increased risk of gastric cancer (per allele
      odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29, p = 0.030).
      This association was more prominent in females (per allele OR = 1.42, 95% CI =
      1.11-1.81, p = 0.005) and nonsmokers (per allele OR = 1.35, 95% CI = 1.14-1.59, p
      = 0.001). Interestingly, we detected a negative interaction between rs5275 and
      smoking on the gastric cancer risk (p = 0.007). Our findings indicate that PTGS2
      rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility.

PMID- 22385257
TI  - Mechanisms and kinetics for the thermal decomposition of 2-azido-N,N
      dimethylethanamine (DMAZ).
AB  - To gain insight into the mechanisms and kinetics of 2-azido-N,N
      dimethylethanamine's (DMAZ's) thermal decomposition postulated reaction paths
      were simulated with ab initio and density functional theory quantum chemistry
      models. Four reaction types were modeled: (i) spin-allowed and spin-forbidden
      paths involving N-N(2) bond fission and nitrene formation, (ii) HN(3) elimination
      with the formation of (dimethylamino)ethylene, (iii) N-N(2) bond fission with the
      formation of molecules with three- or four-membered heterocyclic rings, and (iv)
      simple scission of C-H, C-N, and C-C bonds. The geometries of stationary points
      of the reactions were obtained with a MPWB1K/6-31+G(d,p) model. To locate and
      model the geometries of minimum energy intersystem crossing points for triplet
      nitrene formation and isomerization, unrestricted broken spin symmetry
      calculations were performed. Employed to model an analogous path for methyl
      azide's decomposition, this approach was found to yield results similar to those
      obtained with a CASSCF(10,8)/aug-cc-pVDZ model. Of the four reaction types
      studied, N-N(2) bond fissions with singlet or triplet nitrene formation were
      found to have the lowest barriers. Barriers for paths to cyclic products were
      found to be 2-4 kcal/mol higher. Kinetic rate expressions for individual paths
      were derived from the quantum chemistry results, and spin-allowed nitrene
      formation was found to be dominant at all temperatures and pressures examined.
      The expression 2.69 * 10(9) (s(-1))T(1.405) exp(-39.0 (kcal/mol)/RT), which was
      derived from QCISD(T)/6-31++G(3df,2p)//MPWB1K/6-31+G(d,p) results, was found to
      be representative of this reaction's gas-phase rate. Adjusted on the basis of
      results from self-consistent reaction field models to account for solvation by n
      dodecane, the expression became 1.11 * 10(9) (s(-1))T(1.480) exp(-37.6
      (kcal/mol)/RT). Utilizing this result and others derived in the study, a model of
      the decomposition of n-dodecane-solvated DMAZ was constructed, and it generated
      simulations that well-reproduce previously published measured data for the
      process.

PMID- 22385258
TI  - Ab initio thermodynamics examination of sulfur species present on Rh, Ni, and
      binary Rh-Ni surfaces under steam reforming reaction conditions.
AB  - The stable form of adsorbed sulfur species and their coverage were investigated
      on Rh, Ni, and Rh-Ni binary metal surfaces using density functional theory
      calculations and the ab initio thermodynamics framework. S adsorption, SO(x) (x =
      1-4) adsorption, and metal sulfide formation were examined on Rh(111) and Ni(111)
      pure metals. Both Rh and Ni metals showed a preference for S surface adsorption
      rather than SO(x) adsorption under steam reforming conditions. The transition
      temperature from a clean surface (<(1)/(9) ML) to S adsorption was identified on
      Rh(111), Ni(111), Rh(1)Ni(2)(111), and Rh(2)Ni(1)(111) metals at various
      P(H(2))/P(H(2)S) ratios. Bimetallic Rh-Ni metals transition to a clean surface at
      lower temperatures than does the pure Rh metal. Whereas Rh is covered with
      (1)/(3) ML of sulfur under the reforming conditions of 4-100 ppm S and 800 
      degrees C, Rh(1)Ni(2) is covered with (1)/(9) ML of sulfur at the lower end of
      this range (4-33 ppm S). The possibility of sulfate formation on Rh catalysts was
      examined by considering higher oxygen pressures, a Rh(221) stepped surface, and
      the interface between a Rh(4) cluster and CeO(2)(111) surface. SO(x) surface
      species are stable only at high oxygen pressure or low temperatures outside those
      relevant to the steam reforming of hydrocarbons.

PMID- 22385259
TI  - The assessment of preschool children's participation: internal consistency and
      construct validity.
AB  - Participation in activities provides the means for young children to learn, play,
      develop skills, and develop a sense of personal identity. The Assessment of
      Preschool Children's Participation (APCP) is a newly developed measure to capture
      the participation of children aged 2 to 5 years and 11 months in the areas of
      play, skill development, active physical recreation, and social activities. Data
      from a clinical trial involving 120 children with cerebral palsy indicated that
      the APCP has moderate to very good internal consistency. The measure
      distinguishes between children below or above 4 years of age across levels of the
      Gross Motor Classification System, and between income levels below or above the
      median regional income range. The APCP, with a focus on preschool children, has
      potential use for assessment and identification of activity areas in which the
      child is participating and areas in which participation may be restricted.

PMID- 22385260
TI  - Regenerative therapy of infrabony defects with or without systemic doxycycline. A
      randomized placebo-controlled trial.
AB  - AIM: Comparison of regenerative therapy of infrabony defects with and without
      administration of postsurgical systemic doxycycline (DOXY). METHODS: In each of
      61 patients one infrabony defect was treated with enamel matrix derivative (EMD),
      EMD plus filler or membrane at two centres. By random assignment patients
      received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery.
      Prior to and 6 months after surgery probing pocket depths (PPD) and vertical
      attachment level (PAL-V) were obtained. RESULTS: Fifty-four patients (DOXY: 27;
      PLAC: 27) were re-examined after 6 months and had been treated exclusively with
      EMD. Seven to 8 days after surgery 81% of defects in both groups showed complete
      flap closure. In both groups significant (p < 0.001) PPD reduction (DOXY: 3.87 +/
      1.44 mm; PLAC: 3.67 +/- 1.30 mm) and PAL-V gain (DOXY: 3.11 +/- 1.50 mm; PLAC:
      3.32 +/- 1.83 mm) were observed. However, the differences failed to be
      statistically significant (PPD: 0.20; p = 0.588; PAL-V: 0.21; p = 0.657).
      CONCLUSIONS: Two hundred milligram systemic DOXY administered for 7 days after
      therapy of infrabony defects with EMD failed to result in better PPD reduction
      and PAL-V gain compared with PLAC which may be due to low power (50%) and, thus,
      random chance.

PMID- 22385261
TI  - Highly active Pt3Pb and core-shell Pt3Pb-Pt electrocatalysts for formic acid
      oxidation.
AB  - Formic acid is a promising chemical fuel for fuel cell applications. However, due
      to the dominance of the indirect reaction pathway and strong poisoning effects,
      the development of direct formic acid fuel cells has been impeded by the low
      activity of existing electrocatalysts at desirable operating voltage. We report
      the first synthesis of Pt(3)Pb nanocrystals through solution phase synthesis and
      show they are highly efficient formic acid oxidation electrocatalysts. The
      activity can be further improved by manipulating the Pt(3)Pb-Pt core-shell
      structure. Combined experimental and theoretical studies suggest that the high
      activity from Pt(3)Pb and the Pt-Pb core-shell nanocrystals results from the
      elimination of CO poisoning and decreased barriers for the dehydrogenation steps.
      Therefore, the Pt(3)Pb and Pt-Pb core-shell nanocrystals can improve the
      performance of direct formic acid fuel cells at desired operating voltage to
      enable their practical application.

PMID- 22385262
TI  - The Nedd4-like ubiquitin E3 ligases target angiomotin/p130 to ubiquitin-dependent
      degradation.
AB  - AMOT (angiomotin) is a membrane-associated protein that is expressed in ECs
      (endothelial cells) and controls migration, TJ (tight junction) formation, cell
      polarity and angiogenesis. Recent studies have revealed that AMOT and two AMOT
      like proteins, AMOTL1 and AMOTL2, play critical roles in the Hippo pathway by
      regulating the subcellular localization of the co-activators YAP (Yes-associated
      protein) and TAZ (transcriptional co-activator with PDZ-binding motif). However,
      it has been unclear how AMOT is regulated. In the present study, we report that
      AMOT undergoes proteasomal degradation. We identify three members of Nedd4
      (neural-precursor-cell-expressed developmentally down-regulated)-like ubiquitin
      E3 ligases, Nedd4, Nedd4-2 and Itch, as the ubiquitin E3 ligases for the long
      isoform of AMOT, AMOT/p130. We demonstrate that Nedd4, Nedd4-2 and Itch mediate
      poly-ubiquitination of AMOT/p130 in vivo. Overexpression of Nedd4, Nedd4-2 or
      Itch leads to AMOT/p130 proteasomal degradation. Knockdown of Nedd4, Nedd4-2 and
      Itch causes an accumulation of steady-state level of AMOT/p130. We also show that
      three L/P-PXY motifs of AMOT/p130 and the WW domains of Nedd4 mediate their
      interaction. Furthermore, Nedd4-like ubiquitin E3 ligases might compete with YAP
      for the binding to AMOT/p130, and subsequently targeting AMOT/p130 for ubiquitin
      dependent degradation. Together, these observations reveal a novel post
      translational regulatory mechanism of AMOT/p130.

PMID- 22385263
TI  - Rhinosinusitis and mold as risk factors for asthma symptoms in occupants of a
      water-damaged building.
AB  - Mold exposure in damp buildings is associated with both nasal symptoms and asthma
      development, but the progression of building-related (BR) rhinosinusitis symptoms
      to asthma is unstudied. We examined the risk of developing BR-asthma symptoms in
      relation to prior BR-rhinosinusitis symptoms and microbial exposure among
      occupants of a damp building. We conducted four cross-sectional health and
      environmental surveys among occupants of a 20-story water-damaged office
      building. We defined BR-rhinosinusitis symptom (N=131) and comparison (N=361)
      groups from participants' first questionnaire responses. We compared the odds for
      the development of BR-asthma symptoms between these two groups over the
      subsequent surveys, using logistic regression models adjusted for demographics,
      smoking, building tenure, and first-survey exposures to fungi, endotoxin, and
      ergosterol. The BR-rhinosinusitis symptom group had higher odds for developing BR
      asthma symptoms [odds ratio (OR)=2.2; 95% confidence interval (CI)=1.3-3.6] in
      any subsequent survey compared to those without BR-rhinosinusitis symptoms. The
      BR-rhinosinusitis symptom group with higher fungal exposure within the building
      had an OR of 7.4 (95% CI=2.8-19.9) for developing BR-asthma symptoms, compared to
      the lower fungal exposure group without BR-rhinosinusitis symptoms. Our findings
      suggest that rhinosinusitis associated with occupancy of water-damaged buildings
      may be a sentinel for increased risk for asthma onset in such buildings.
      PRACTICAL IMPLICATIONS: Exposure to mold is associated with the development of
      asthma in damp building occupants, and rhinitis is known to be a risk factor for
      asthma. However, there is little information about the degree of risk for the
      progression of rhinosinusitis to asthma owing to mold exposures in damp
      buildings. Our study of damp building occupants demonstrates that building
      related (BR) rhinosinusitis symptoms were a risk factor for the development of BR
      asthma symptoms and that exposure to mold (fungi) or other dampness-related
      agents augments risk for the development of BR asthma symptoms among those with
      BR rhinosinusitis symptoms. Our findings suggest that occurrence of BR upper
      respiratory illness in water-damaged buildings may presage future endemic asthma.

PMID- 22385264
TI  - Role of hydroxyl radicals and mechanism of Escherichia coli inactivation on
      Ag/AgBr/TiO2 nanotube array electrode under visible light irradiation.
AB  - A ternary Ag/AgBr/TiO(2) nanotube array electrode with enhanced visible-light
      activity was synthesized by a two-step approach including electrochemical process
      of anodization and an in situ photoassisted deposition strategy. The dramatically
      enhanced photoelectrocatalytic activity of the composite electrode was evaluated
      via the inactivation of Escherichia coli under visible light irradiation
      (lambda>420 nm), whose performance of complete sterilization was much superior to
      other reference photocatalysts. PL, ESR, and radicals trapping studies revealed
      hydroxyl radicals were involved as the main active oxygen species in the
      photoelectrocatalytic reaction. The process of the damage of the cell wall and
      the cell membrane was directly observed by ESEM, TEM, and FTIR, as well as
      further confirmed by determination of potassium ion leakage from the killed
      bacteria. The present results pointed to oxidative attack from the exterior to
      the interior of the Escherichia coli by OH(*), O(2)(*-), holes and Br(0), causing
      the cell to die as the primary mechanism of photoelectrocatalytic inactivation.

PMID- 22385265
TI  - Socio-economic disadvantage at the area level poses few direct barriers to
      smoking cessation for Australian smokers: findings from the International Tobacco
      Control Australian cohort survey.
AB  - INTRODUCTION: Area-level indicators of socio-economic variation are frequently
      included in models of individual health outcomes. Area disadvantage is linearly
      related to smoking prevalence, but its relation to cessation outcomes is less
      well understood. AIMS: To explore the relationship between area-level
      disadvantage and prospective data on smoking cessation. DESIGN AND METHODS: The
      Australian cohort of the International Tobacco Control Four-Country Survey (N =
      3503) was used to prospectively examine the contribution of area-level socio
      economic disadvantage to predicting three important smoking-cessation outcomes:
      making a quit attempt, achieving 1 month abstinence and achieving 6 month
      abstinence from smoking, while controlling for individual-level socio-economic
      indicators and other individual-level covariates related to smoking cessation.
      RESULTS: Only two independent associations were observed between socio-economic
      disadvantage and cessation outcomes. Area-level disadvantage was related to 1
      month abstinence in a non-linear fashion, and the individual experience of
      smoking-induced deprivation was associated with a lower likelihood of making quit
      attempts. DISCUSSION: Despite the documented higher prevalence of smoking among
      the more disadvantaged and in more disadvantaged areas, socio-economic
      disadvantage was not consistently related to making quit attempts, nor to medium
      term success. Nevertheless, indirect effects of disadvantage, like its impact on
      psychological distress, cannot be ruled out, and considering smokers' individual
      psychosocial circumstances is likely to aid cessation efforts. CONCLUSION: Socio
      economic disadvantage, particularly at the area level, poses few direct barriers
      to smoking cessation.

PMID- 22385266
TI  - The butter flavorant, diacetyl, forms a covalent adduct with 2-deoxyguanosine,
      uncoils DNA, and leads to cell death.
AB  - Diacetyl (DA), a natural butter flavorant, is a causative agent for the lung
      disease obliterative bronchiolitis. Mutagenic properties of 1,2-dicarbonyls have
      previously been empirically linked to their possible interaction with DNA
      nucleobases. This study for the first time identifies chemically the adduct of DA
      with 2-deoxyguanosine. Selective reactivity of DA with 5'-TTTGTTTTT-3' over 5'
      TTTTTTTTT-3' indicated its propensity to modify specifically the guanosine
      residue. Treatment of plasmid DNA, pBR322, with DA induced changes in
      electrophoretic mobility that are typical of ternary structure disruption. Such
      DNA nucleobase interaction of DA translated into increased apoptosis in DA
      treated SH-SY5Y cells in a dose-dependent manner (IC(50) = 0.114 +/- 0.0421 mM).
      The traditional carbonyl scavengers metformin, 2-thiobarbituric acid, and d
      penicillamine protected cells from DA toxicity in proportion to their rates of
      reaction with DA, with d-penicillamine causing a maximal increase in the IC(50)
      to 5.23 +/- 0.0992 mM when co-incubated with DA.

PMID- 22385267
TI  - Perioperative management of the morbidly obese adolescent with heart failure
      undergoing bariatric surgery.
AB  - The incidence and prevalence of adolescent obesity and adolescent heart failure
      are increasing, and anesthesiologists increasingly will encounter patients with
      both conditions. A greater understanding of the physiologic challenges of
      adolescent heart failure as they relate to the perioperative stressors of
      anesthesia and bariatric surgery is necessary to successfully manage the
      perioperative risks faced by this growing subpopulation. Here, we present a
      representative case of a morbidly obese adolescent with heart failure who
      underwent a laparoscopic bariatric operation and review the limited available
      literature on perioperative management in this age group. Specifically, we review
      evidence and offer recommendations related to preoperative evaluation, venous
      thromboembolism prophylaxis, positioning, induction, airway management,
      monitoring, anesthetic maintenance, ventilator management, and adverse effects of
      the pneumoperitoneum, rhabdomyolysis, and postoperative care.

PMID- 22385268
TI  - Regulation of a quorum sensing system by stationary phase sigma factor RpoS and
      their co-regulation of target genes  in Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is the causative agent of a fatal disease, melioidosis.
      However, the mechanisms of pathogenesis and genes involved in its virulence are
      not understood. In the current study, whether stationary phase and stress
      response sigma factor RpoS and BpsI-mediated quorum sensing (QS) system co
      regulate its target genes was investigated. Positive regulation of RpoS on bpsI
      expression and autoinducer production in stationary phase, but not on fliC and
      ppk expression, was observed. In contrast, expression of rpoS was not affected by
      deletion of bpsI. The present results also indicate that production of
      extracellular protease and siderophore, two QS-controlled exo products, is
      regulated via RpoS supporting the previously known inhibitory role of QS on those
      two factors. Proteomic analysis revealed that expression of 74 protein spots
      representing 60 genes is controlled by QS. Of those, 45 genes are co-regulated by
      both RpoS and QS, and regulation of genes involved in transcription and
      translation is favored by QS. Taken together, our findings indicate major target
      genes expression in stationary phase that is influenced by hierarchical control
      of RpoS over QS. We propose that this regulation may play an important role in
      the pathogenicity of B. pseudomallei.

PMID- 22385269
TI  - Type I cryoglobulinemia in multiple myeloma, a rare entity: analysis of clinical
      and biological characteristics of seven cases and review of the literature.
AB  - The type I cryoglobulins (CGs) account for 10-15% of all cryoglobulins and are
      found in patients with hematological disorders. We here describe the largest
      series of seven cases of type I cryoglobulinemia associated with multiple myeloma
      (MM) and provide a detailed review of the literature associated with this
      disorder, with the aim of improving the future diagnosis and therapeutic
      management of this rare disease. Six of the cases in our series were men aged 28
      69 years, and most of the subject patients had an immunoglobulin G (IgG)
      monoclonal component and stage I indolent MM that manifested as cryoglobulin
      related symptoms. The patients were all karyotypically normal. Clinical
      manifestations in this group were: skin lesions (five cases, 71.4%),
      rheumatologic failure (four cases, 57.1%), neurological abnormalities (two cases,
      28.6%), mixed cutaneous/rheumatologic/renal defects (one case, 14.3%) and one
      case in which the cryoglobulinemia was asymptomatic. Two patients experienced
      acute renal failure but underwent a full recovery following treatment for MM. We
      conclude from our analysis that treatment approaches for severe type I
      cryoglobulinemia should involve plasmapheresis at the onset to achieve a rapid
      control of the CG-related symptoms, and that specific MM treatments should be
      introduced also at an early stage to avoid cryoglobulinemia relapse. In this
      context, bortezomib and lenalidomide are potentially the most effective
      therapeutic agents.

PMID- 22385270
TI  - Diagnostic value of the serum galactomannan assay for invasive aspergillosis: it
      is less useful in non-haematological patients.
AB  - BACKGROUND: The serum galactomannan assay (GMA) has been widely used for the
      diagnosis of invasive aspergillosis (IA). GMA is mainly used in patients with
      haematological malignancies or in those who have undergone haematopoietic stem
      cell transplantation (HSCT). However, there are few data from non-haematological
      patients. We evaluated whether GMA is useful for the diagnosis of IA in non
      haematological patients. METHODS: Patients who were subjected to serum GMA
      testing from January 2007 to December 2009 were evaluated retrospectively.
      Patients with haematological diseases or who underwent HSCT were excluded from
      our analysis. According to the criteria of the European Organization for Research
      and Treatment of Cancer/Mycoses Study Group revised in 2008, the patients were
      categorized as proven, probable, possible, or non-IA. Proven and probable cases
      were defined as IA in this study. RESULTS: Out of 778 patients, 13 (1.6%) had
      proven (n =9) or probable (n =4) IA. The sensitivity of the GMA was 23.1% (95%
      confidence interval (CI) 6.1-54.0%) and the specificity was 76.1% (95% CI 72.9
      79.0%). The positive predictive value was 1.6% (95% CI 0.4-5.0%) and the negative
      predictive value was 98.3% (95% CI 96.8-99.1%). The likelihood ratios of a
      positive and negative test were 0.96 (95% CI 0.35-2.62) and 1.01 (95% CI 0.75
      1.36), respectively. CONCLUSIONS: In this study, the sensitivity of the GMA for
      the diagnosis of IA was very low in non-haematological patients. Although the GMA
      test is considered useful for the diagnosis of IA in haematological patients, it
      had low diagnostic value for IA in non-haematological patients.

PMID- 22385271
TI  - Autophagy in hypoxia-ischemia induced brain injury.
AB  - Autophagy is an endogenous tightly regulated process responsible for the
      degradation of damaged and dysfunctional cellular organelles and protein
      aggregates. Emerging data indicate a strong and complex interaction among
      autophagy, apoptosis and necrosis. We studied these interactions in a neonatal
      model of hypoxia-ischemia (HI). Autophagy was assessed by evaluating the
      expression of the two autophagy proteins beclin 1 and LC3, and by "in vivo"
      autophagic vesicles formation and clearance using monodansylcadaverine (MDC).
      Both autophagy and apoptosis pathways were increased in the same neurons at short
      times after HI. Neuroprotective drugs also increased autophagy. Interestingly,
      pharmacological inhibition of autophagy switched cell death phenotypes from
      apoptosis to necrosis. Rapamycin, that enhances autophagy by inhibition of mTOR
      and previously shown to be neuroprotective in our animal model of HI when
      administered before the ischemic insult, was used to study the potential
      interaction between autophagy and survival pathways. Rapamycin, besides inducing
      autophagy, also increased Akt and CREB (cAMP response element-binding protein)
      phosphorylation in the same cells. The pharmacological inhibition of the
      phosphatidylinositol 3-kinase (PI3K)/Akt axis reduced the neuroprotective effect
      of rapamycin without affecting autophagy. Conversely, pharmacological inhibition
      of autophagy reduced the neuroprotective effect of rapamycin without affecting
      Akt phosphorylation. Both treatments, however, caused a rapid switch towards
      necrotic cell death. Thus, autophagy can be part of an integrated pro-survival
      signalling which includes the PI3K-Akt- mTOR axis and its activation seems be
      crucial for pharmacological and ischemic preconditioning.

PMID- 22385272
TI  - Chemical composition and antibacterial activity of the essential oil from Mentha
      requienii Bentham.
AB  - The chemical composition of essential oil obtained by hydrodistillation of the
      fresh aerial parts of Mentha requienii Bentham (Lamiaceae) collected on the
      Gennargentu Mountains (Sardinia, Italy) has been investigated by gas
      chromatography and gas chromatography-mass spectrometry. The main constituents
      that resulted were pulegone (78%), menthone (0.5%), isomenthone (18%),
      isopulegone (1.3%) and limonene (1.76%). In vitro antifungal activity is
      evaluated in order to identify new means that could be helpful in the prevention
      of contamination in indoor environments.

PMID- 22385273
TI  - Influence of an immunopotentiator Polyoxidonium on cytokine profile and antibody
      production in children vaccinated with Priorix.
AB  - 60 children aged 1-2 years old (32 boys and 28 girls) were vaccinated with
      Priorix. Vaccinated children included healthy control (19 children, group 1), and
      children with immunological disturbances such as episodes of respiratory
      infection. From the latter group, 20 children did not receive (group 2), and 21
      children received 0.15 mg/kg of Polyoxidonium simultaneously with the vaccine
      (group 3).On days 7 and 30 after vaccination, CD-markers on lymphocytes and
      concentration of specific antibodies, as well as levels of 11 cytokines in serum
      were evaluated by flow cytometry, ELISA, and multiplex techniques respectively.
      It was found that injection of Polyoxidonium skewed T helper differentiation to
      Th2 type. Antibody responses were significantly higher in children with
      preferable Th2 responses. Children from group 3 possessed higher titers of
      specific IgG-antibodies. Our study shows that Polyoxidonium could smooth out the
      immune reaction on vaccination. It is important for children with some
      immunological disturbances.

PMID- 22385274
TI  - Stereoselective C-glycosylation reactions with arylzinc reagents.
AB  - A general, transition-metal-free, highly stereoselective cross-coupling reaction
      between glycosyl bromides and various arylzinc reagents leading to beta-arylated
      glycosides is reported. The stereoselectivity of the reaction is explained by
      invoking anchimeric assistance via a bicyclic intermediate. Stereochemical probes
      confirm the participation of the 2-pivaloyloxy group. Finally, this new method
      was applied to a short and efficient stereoselective synthesis of Dapagliflozin
      and Canagliflozin.

PMID- 22385276
TI  - Green synthesis of gold-chitosan nanocomposites for caffeic acid sensing.
AB  - In this work, colloidal gold nanoparticles (AuNPs) stabilized into a chitosan
      matrix were prepared using a green route. The synthesis was carried out by
      reducing Au(III) to Au(0) in an aqueous solution of chitosan and different
      organic acids (i.e., acetic, malonic, or oxalic acid). We have demonstrated that
      by varying the nature of the acid it is possible to tune the reduction rate of
      the gold precursor (HAuCl(4)) and to modify the morphology of the resulting metal
      nanoparticles. The use of chitosan, a biocompatible and biodegradable polymer
      with a large number of amino and hydroxyl functional groups, enables the
      simultaneous synthesis and surface modification of AuNPs in one pot. Because of
      the excellent film-forming capability of this polymer, AuNPs-chitosan solutions
      were used to obtain hybrid nanocomposite films that combine highly conductive
      AuNPs with a large number of organic functional groups. Herein, Au-chitosan
      nanocomposites are successfully proposed as sensitive and selective
      electrochemical sensors for the determination of caffeic acid, an antioxidant
      that has recently attracted much attention because of its benefits to human
      health. A linear response was obtained over a wide range of concentration from
      5.00 * 10(-8) M to 2.00 * 10(-3) M, and the limit of detection (LOD) was
      estimated to be 2.50 * 10(-8) M. Moreover, further analyses have demonstrated
      that a high selectivity toward caffeic acid can be achieved without interference
      from catechin or ascorbic acid (flavonoid and nonphenolic antioxidants,
      respectively). This novel synthesis approach and the high performances of Au
      chitosan hybrid materials in the determination of caffeic acid open up new routes
      in the design of highly efficient sensors, which are of great interest for the
      analysis of complex matrices such as wine, soft drinks, and fruit beverages.

PMID- 22385275
TI  - Catalytic mechanism of aromatic prenylation by NphB.
AB  - NphB is an aromatic prenyltransferase that catalyzes the attachment of a 10
      carbon geranyl group to aromatic substrates. Importantly, NphB exhibits a rich
      substrate selectivity and product regioselectivity. A systematic computational
      study has been conducted in order to address several question associated with
      NphB-catalyzed geranylation. The reaction mechanism of the prenylation step has
      been characterized as a S(N)1 type dissociative mechanism with a weakly stable
      carbocation intermediate. A novel pi-chamber composed of Tyr121, Tyr216, and 1,6
      DHN is found to be important in stabilizing the carbocation. The observed
      difference in the rates of product formation from 5- and 2-prenylation arises
      from the differing orientations of the aromatic substrate in the resting state. 4
      Prenylation shares the same resting state with 5-prenylation, but the lower free
      energy barrier for carbocation formation makes the latter reaction more facile.
      The high free energy barrier associated with 7-prenylation is caused by the
      unfavorable orientation of 1,6-DHN in active site pocket, along with the
      difficulty of proton elimination after the prenylation step. A water-mediated
      proton transfer facilitates the loss of hydrogen at the prenylation site to form
      the final prenylated product. Interestingly, the same crystallographically
      observed water molecule has been found to be responsible for proton loss in all
      three experimentally identified products. After proton transfer, the relaxation
      of the final product from a sp(3) carbon center to a sp(2) center triggers a
      "spring-loaded" product release mechanism which pushes the final product out of
      the binding pocket toward the edge of the active site. The hydrogen bond
      interactions between the two hydroxyl groups of the aromatic product and the side
      chains of Ser214 and Tyr288 help to "steer" the movement of the product. In
      addition, mutagenesis studies identify these same two side chains as being
      responsible for the observed regioselectivity, particularly 2-prenylation. These
      observations provide valuable insights into NphB chemistry, offering an
      opportunity to better engineer the active site and to control the reactivity in
      order to obtain high yields of the desired product(s). Furthermore, the S(N)1
      reaction mechanism observed for NphB differs from the prenylation reaction found
      in, for example, the farnesyltransferase, which proceeds via an S(N)2-like
      reaction pathway. The spring-loaded release mechanism highlighted herein also
      offers novel insights into how enzymes facilitate product release.

PMID- 22385277
TI  - Live-cell visualization of transmembrane protein oligomerization and membrane
      fusion using two-fragment haptoEGFP methodology.
AB  - Protein interactions play key roles throughout all subcellular compartments. In
      the present paper, we report the visualization of protein interactions throughout
      living mammalian cells using two oligomerizing MV (measles virus) transmembrane
      glycoproteins, the H (haemagglutinin) and the F (fusion) glycoproteins, which
      mediate MV entry into permissive cells. BiFC (bimolecular fluorescence
      complementation) has been used to examine the dimerization of these viral
      glycoproteins. The H glycoprotein is a type II membrane-receptor-binding
      homodimeric glycoprotein and the F glycoprotein is a type I disulfide-linked
      membrane glycoprotein which homotrimerizes. Together they co-operate to allow the
      enveloped virus to enter a cell by fusing the viral and cellular membranes. We
      generated a pair of chimaeric H glycoproteins linked to complementary fragments
      of EGFP (enhanced green fluorescent protein)--haptoEGFPs--which, on association,
      generate fluorescence. Homodimerization of H glycoproteins specifically drives
      this association, leading to the generation of a fluorescent signal in the ER
      (endoplasmic reticulum), the Golgi and at the plasma membrane. Similarly, the
      generation of a pair of corresponding F glycoprotein-haptoEGFP chimaeras also
      produced a comparable fluorescent signal. Co-expression of H and F glycoprotein
      chimaeras linked to complementary haptoEGFPs led to the formation of fluorescent
      fusion complexes at the cell surface which retained their biological activity as
      evidenced by cell-to-cell fusion.

PMID- 22385278
TI  - Alignment of small organic solutes in a nematic solvent: the effect of
      electrostatic interactions.
AB  - The origin of the alignment with respect to the director observed for solutes in
      a nematic host remains unclear, and various mechanisms ranging from steric
      repulsions to dispersive or electrostatic interactions have been invoked. Here we
      present atomistic molecular dynamics (MD) computer simulations of rigid solutes
      of small dimensions dissolved in a nematic liquid crystal solvent, 4-n-pentyl
      4'cyanobiphenyl (5CB), that aim to quantitatively predict the orientational
      order. We have validated the results comparing the dipolar couplings obtained by
      atomistic simulation with their experimental NMR counterparts. To help assess the
      separate effect of the various types of anisotropic interactions on the
      orientational order of solutes, we have modeled solute molecules with their
      partial atomic charges present or absent (switching them to zero), finding that,
      at least for the cases studied, the alignment mechanism is largely dominated by
      steric and van der Waals dispersive forces rather than Coulomb ones. We have
      compared the anisotropic aligning potential with the predictions of the Maier
      Saupe and surface tensor models and discussed their performance.

PMID- 22385279
TI  - Mechanistic and kinetic study of CF3CH?CH2 + OH reaction.
AB  - The potential energy surfaces of the CF(3)CH?CH(2) + OH reaction have been
      investigated at the BMC-CCSD level based on the geometric parameters optimized at
      the MP2/6-311++G(d,p) level. Various possible H (or F)-abstraction and
      addition/elimination pathways are considered. Temperature- and pressure-dependent
      rate constants have been determined using Rice-Ramsperger-Kassel-Marcus theory
      with tunneling correction. It is shown that IM1 (CF(3)CHCH(2)OH) and IM2
      (CF(3)CHOHCH(2)) formed by collisional stabilization are major products at 100
      Torr pressure of Ar and in the temperature range of T < 700 K (at P = 700 Torr
      with N(2) as bath gas, T <= 900 K), whereas CH(2)?CHOH and CF(3) produced by the
      addition/elimination pathway are the dominant end products at 700-2000 K. The
      production of CF(3)CHCH and CF(3)CCH(2) produced by hydrogen abstractions become
      important at T >= 2000 K. The calculated results are in good agreement with
      available experimental data. The present theoretical study is helpful for the
      understanding the characteristics of the reaction of CF(3)CH?CH(2) + OH.

PMID- 22385280
TI  - Self-report function and disability: a comparison between women with and without
      urgency urinary incontinence.
AB  - PURPOSE: To compare self-reported function and disability between women with
      urgency urinary incontinence (UUI) and healthy controls. METHOD: Self-reported
      function and disability were evaluated using the Late Life Function and
      Disability Instrument (LLFDI) in 66 women with UUI (mean age 61.9 +/- 5.6) and 66
      age-matched control women without UUI in a cross-sectional study. The function
      component evaluates difficulty in performing physical activities in upper and
      lower extremities and the disability component evaluates limitations in life
      activities and frequency in taking part in life tasks. Body Mass Index (BMI),
      self-report incontinence quality of life questionnaire (I-QoL) and Visual Analog
      Scale (VAS) that indicate the degree to which the bladder problems limited the
      subject's daily life activity were also evaluated. RESULTS: The LLFDI scores in
      overall function, basic and advanced lower limb function, were significantly
      lower in women with UUI compared with continent women, while the upper extremity
      function and disability components were not. There was significant negative
      correlation between BMI and function scores in women with UUI. CONCLUSION: Our
      results support the assumptions that the women with UUI are likely to show poorer
      lower extremity physical functioning and that disability is a multifactorial
      combination of behavioral, psychological and environmental factors, and not
      functional limitations per se.

PMID- 22385281
TI  - Extending signaling pathways with protein-interaction networks. Application to
      apoptosis.
AB  - Cells exploit signaling pathways during responses to environmental changes, and
      these processes are often modulated during disease. Particularly, relevant human
      pathologies such as cancer or viral infections require downregulating apoptosis
      signaling pathways to progress. As a result, the identification of proteins
      responsible for these changes is essential for the diagnostics and development of
      therapeutics. Transferring functional annotation within protein interaction
      networks has proven useful to identify such proteins, although this is not a
      trivial task. Here, we used different scoring methods to transfer annotation from
      53 well-studied members of the human apoptosis pathways (as known by 2005) to
      their protein interactors. All scoring methods produced significant predictions
      (compared to a random negative model), but its number was too large to be useful.
      Thus, we made a final prediction using specific combinations of scoring methods
      and compared it to the proteins related to apoptosis signaling pathways during
      the last 5 years. We propose 273 candidate proteins that may be relevant in
      apoptosis signaling pathways. Although some of them have known functions
      consistent with their proposed apoptotsis involvement, the majority have not been
      annotated yet, leaving room for further experimental studies. We provide our
      predictions at http://sbi.imim.es/web/Apoptosis.php.

PMID- 22385282
TI  - Poly-L-lysine functionalized large pore cubic mesostructured silica nanoparticles
      as biocompatible carriers for gene delivery.
AB  - Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-L
      lysine (PLL) were designed as a new carrier material for gene delivery
      applications. The synthesized LP-MSNs are 100-200 nm in diameter and are composed
      of cage-like pores organized in a cubic mesostructure. The size of the cavities
      is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto
      the silica surface through covalent immobilization was confirmed by X-ray
      photoelectron spectroscopy, solid-state (13)C magic-angle spinning nuclear
      magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis.
      As a result of the particle modification with PLL, a significant increase of the
      nanoparticle binding capacity for oligo-DNAs was observed compared to the native
      unmodified silica particles. Consequently, PLL-functionalized nanoparticles
      exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela
      cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior
      as gene carriers compared to amino-functionalized nanoparticles and the native
      nanoparticles. The system was tested to deliver functional siRNA against
      minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells.
      Here, the functionalized particles demonstrated great potential for efficient
      gene transfer into cancer cells as a decrease of the cellular viability of the
      osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica
      nanoparticles also exhibit a high biocompatibility, with low cytotoxicity
      observed up to 100 MUg/mL.

PMID- 22385283
TI  - Biostimulation of indigenous microbial communities for anaerobic transformation
      of pentachlorophenol in paddy soils of southern China.
AB  - This study explored biostimulation mechanisms with an electron donor and a
      shuttle for accelerating pentachlorophenol (PCP) transformation in iron-rich
      soils. The results indicated that indigenous microbial communities are important
      for PCP transformation in soils. Biostimulation of indigenous microbial
      communities by the addition of lactate and anthraquinone-2,6-disulfonate (AQDS)
      led to the enhanced rates of PCP dechlorination by the dechlorinating- and iron
      reducing bacteria in soils. The electrochemical studies using cyclic
      voltammograms and microbial current measurements confirmed the high reduction
      potential and the large amount of electrons generated under biostimulation
      conditions, which were responsible for the higher rates of PCP transformation.
      After biostimulation treatments by the additions of lactate and/or AQDS during
      PCP dechlorination processes, microbial community analysis by the terminal
      restriction fragment length polymorphism (T-RFLP) method showed the abundance
      terminal restricted fragments (T-RFs), an indicator of bacterial abundance, which
      represents the dechlorinating- and iron-reducing bacteria, suggesting their
      critical roles in PCP dechlorination in soils.

PMID- 22385284
TI  - Children's health and its association with indoor environments in Danish homes
      and daycare centres - methods.
AB  - The principle objective of the Danish research program 'Indoor Environment and
      Children's Health' (IECH) was to explore associations between various exposures
      that children experience in their indoor environments (specifically their homes
      and daycare centers) and their well-being and health. The targeted health
      endpoints were allergy, asthma, and certain respiratory symptoms. The study was
      designed with two stages. In the first stage, a questionnaire survey was
      distributed to more than 17,000 families with children between the ages of 1 and
      5. The questionnaire focused on the children's health and the environments within
      the homes they inhabited and daycare facilities they attended. More than 11,000
      questionnaires were returned. In the second stage, a subsample of 500 children
      was selected for more detailed studies, including an extensive set of
      measurements in their homes and daycare centers and a clinical examination; all
      clinical examinations were carried out by the same physician. In this study, the
      methods used for data collection within the IECH research program are presented
      and discussed. Furthermore, initial findings are presented regarding descriptors
      of the study population and selected characteristics of the children's dwellings
      and daycare centers. PRACTICAL IMPLICATIONS: This study outlines methods that
      might be followed by future investigators conducting large-scale field studies of
      potential connections between various indoor environmental factors and selected
      health endpoints. Of particular note are (i) the two-stage design - a broad
      questionnaire-based survey followed by a more intensive set of measurements among
      a subset of participants who have been selected based on their responses to the
      questionnaire; (ii) the case-base approach utilized in the stage 2 in contrast to
      the more commonly used case-control approach; (iii) the inclusion of the
      children's daycare environment when conducting intensive sampling to more fully
      capture the children's total indoor exposure; and (iv) all clinical examinations
      conducted by the same physician. We recognize that future investigators are
      unlikely to fully duplicate the methods outlined in this study, but we hope that
      it provides a useful starting point in terms of factors that might be considered
      when designing such a study.

PMID- 22385285
TI  - Innovated application of mechanical activation to separate lead from scrap
      cathode ray tube funnel glass.
AB  - The disposal of scrap cathode ray tube (CRT) funnel glass has become a global
      environmental problem due to the rapid shrinkage of new CRT monitor demand, which
      greatly reduces the reuse for remanufacturing. To detoxificate CRT funnel glass
      by lead recovery with traditional metallurgical methods, mechanical activation by
      ball milling was introduced to pretreat the funnel glass. As a result,
      substantial physicochemical changes have been observed after mechanical
      activation including chemical breakage and defects formation in glass inner
      structure. These changes contribute to the easy dissolution of the activated
      sample in solution. High yield of 92.5% of lead from activated CRT funnel glass
      by diluted nitric acid leaching and successful formation of lead sulfide by
      sulfur sulfidization in water have also been achieved. All the results indicate
      that the application of mechanical activation on recovering lead from CRT funnel
      glass is efficient and promising, which is also probably appropriate to
      detoxificate any other kind of leaded glass.

PMID- 22385286
TI  - Stable isotope probing of bacterial community structure and gene expression in
      the rhizosphere of Arabidopsis thaliana.
AB  - The rhizosphere is an active compartment where plant and microorganisms establish
      a molecular dialogue. In this study, we analysed the impact of Arabidopsis
      thaliana on bacterial community structure and the expression of certain
      beneficial genes using DNA- and mRNA-SIP in the rhizosphere of plantlets grown
      under (13)CO(2) for 13, 21 and 27 days. DNA- and rRNA-SIP revealed changes in
      bacterial communities inhabiting the rhizosphere soil that were probably related
      to modification of root exudates, while root-colonizing populations were
      maintained over time suggesting their metabolic versatility and adaptation. The
      impact of the plant via root exudates on the expression of the noncoding RNAs
      rsmZ, acdS gene encoding 1-aminocyclopropane-1-carboxylate deaminase and nosZ
      gene encoding nitrous oxide reductase, in the root-adhering soil and on the roots
      of A. thaliana was determined using mRNA-SIP. Results showed that these genes
      were present and expressed by bacteria inhabiting roots and by those that derive
      nutrients from the breakdown of organic matter in soils or from root exudates.
      The expression of rsmZ under natural conditions indicates the importance of
      noncoding RNAs in bacterial adaptation to their ecological niches.

PMID- 22385287
TI  - Controlled conjugated backbone twisting for an increased open-circuit voltage
      while having a high short-circuit current in poly(hexylthiophene) derivatives.
AB  - Conjugated polymers with nearly planar backbones have been the most commonly
      investigated materials for organic-based electronic devices. More twisted polymer
      backbones have been shown to achieve larger open-circuit voltages in solar cells,
      though with decreased short-circuit current densities. We systematically impose
      twists within a family of poly(hexylthiophene)s and examine their influence on
      the performance of polymer:fullerene bulk heterojunction (BHJ) solar cells. A
      simple chemical modification concerning the number and placement of alkyl side
      chains along the conjugated backbone is used to control the degree of backbone
      twisting. Density functional theory calculations were carried out on a series of
      oligothiophene structures to provide insights on how the sterically induced
      twisting influences the geometric, electronic, and optical properties. Grazing
      incidence X-ray scattering measurements were performed to investigate how the
      thin-film packing structure was affected. The open-circuit voltage and charge
      transfer state energy of the polymer:fullerene BHJ solar cells increased
      substantially with the degree of twist induced within the conjugated backbone-
      due to an increase in the polymer ionization potential--while the short-circuit
      current decreased as a result of a larger optical gap and lower hole mobility. A
      controlled, moderate degree of twist along the poly(3,4-dihexyl-2,2':5',2''
      terthiophene) (PDHTT) conjugated backbone led to a 19% enhancement in the open
      circuit voltage (0.735 V) vs poly(3-hexylthiophene)-based devices, while similar
      short-circuit current densities, fill factors, and hole-carrier mobilities were
      maintained. These factors resulted in a power conversion efficiency of 4.2% for a
      PDHTT:[6,6]-phenyl-C(71)-butyric acid methyl ester (PC(71)BM) blend solar cell
      without thermal annealing. This simple approach reveals a molecular design avenue
      to increase open-circuit voltage while retaining the short-circuit current.

PMID- 22385288
TI  - Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary
      adenoma, and papillary thyroid carcinoma.
AB  - BACKGROUND: Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic
      pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid
      occurred concurrently in a patient. A genetic mutation was hypothesized. Possible
      previously described genetic mutations were explored. METHODS: Clinical
      assessments, laboratory data, images of tumors, histopathology, and
      immunohistochemistry of excised tissues documented the three neoplasms. Clinical
      assessment of the patient, family history, and a review of the literature sought
      a familial basis for the disorders. RESULTS: The methods confirmed the presence
      of three endocrine neoplasms. Each neoplasm was surgically excised and
      histologically verified. Surgical and (131)I treatments reduced the papillary
      carcinoma, but eventually this tumor progressed to a lethal degree. History,
      including that of nine siblings, uncovered no familial neoplasms. No similar case
      was found in the literature, but possible associations with germline mutations
      were considered. CONCLUSIONS: The concurrent development of pheochromocytomas,
      pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be
      unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas,
      strongly suggest a de novo germline mutation in a gene not previously associated
      with multiple endocrine neoplasia syndromes.

PMID- 22385289
TI  - Graves' orbitopathy results in profound changes in tear composition: a study of
      plasminogen activator inhibitor-1 and seven cytokines.
AB  - BACKGROUND: Secretion of cytokines and expression of cytokine receptors have been
      reported in the orbital connective tissue in Graves' orbitopathy (GO). Lacrimal
      glands are putative autoimmune targets, and changes in tear film and ocular
      surface have also been described. Our aim was to characterize the cytokine
      profile of tears in patients with Graves' disease (GD) with and without
      orbitopathy. METHODS: Tear samples were collected from 54 eyes of GO patients
      (age 43.4+/-15.2 years), 18 eyes of GD patients (age 46.8+/-11.7 years), and 24
      control eyes (age 38.6+/-13.8 years). Patients underwent ophthalmological
      examination including Clinical Activity Score (CAS). The level of interleukin
      (IL)-1beta, IL-6, IL-13, IL-17A, IL-18, tumor necrosis factor (TNF)-alpha, and
      RANTES (regulated upon activation, normal T-cell expressed, and secreted) as well
      as plasminogen activator inhibitor-1 (PAI-1) were measured by multiplex bead
      array and release values were calculated. RESULTS: The release of IL-1beta, IL-6,
      IL-13, IL-17A, IL-18, TNF-alpha, and RANTES were significantly higher in GO
      patients compared to controls (p<0.05). There was a 2.5-fold increase of IL-6
      release. No significant differences were found in cytokine release between the GO
      and GD groups. In the GO group, significant positive correlation was found
      between CAS and the release of IL-6 and PAI-1 into tears (r=0.27, p<0.05 and
      r=0.24, p<0.05, respectively). PAI-1 release was significantly higher in GO than
      in GD patients and was increased in both the GD and GO groups compared to
      controls. CONCLUSIONS: Impaired cytokine balance has been observed in tears of GO
      patients. Secretion of IL-6 into tears might be a useful indicator of disease
      activity in GO.

PMID- 22385290
TI  - Thyroid lobe ablation with radioactive iodine as an alternative to completion
      thyroidectomy after hemithyroidectomy in patients with follicular thyroid
      carcinoma: long-term follow-up.
AB  - BACKGROUND: Radioactive iodine lobe ablation (RAI-L-ABL) is a possible
      alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma
      (FTC), but no long-term outcome data are available after lobe ablation. We
      analyzed the long-term outcome of lobe ablation in a series of patients with FTC.
      METHODS: This was a retrospective study of patients who were treated with lobe
      ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe
      ablation with (131)I (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%)
      had initial total thyroidectomy (T-Tx). The main outcomes analyzed were (131)I
      uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid
      stimulating hormone (TSH), long-term disease-specific mortality, and disease-free
      survival. RESULTS: After lobe ablation, radioiodine uptake was significantly
      lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T
      Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37
      (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx
      group, and in 25 of 29 (86.2%) patients in the T-Tx group (p<0.01). With median
      follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and
      53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one
      death in the T-Tx group. No other RAI-L-ABL patients had detectable disease,
      whereas patients in the C-Tx group and two patients in the T-Tx group had
      detectable disease (p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL
      were found in 87.5% of the RAI-L-ABL group (n=28), 86.3% of the C-Tx group
      (n=57), and 77.8% of the T-Tx group (n=21). Tg was detectable in 40.6% of the RAI
      L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p<0.05, between
      groups). CONCLUSIONS: RAI-L-ABL, C-Tx, and T-Tx are equally effective in
      achieving serum TSH concentrations of >25 mIU/L and preparing patients for
      conventional (131)I treatment and whole body scanning with similar long-term
      outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common
      after RAI-L-ABL.

PMID- 22385291
TI  - Insights into early brain development.

PMID- 22385292
TI  - Assessment of the human faecal microbiota: II. Reproducibility and associations
      of 16S rRNA pyrosequences.
AB  - BACKGROUND: We conducted a pilot study of reproducibility and associations of
      microbial diversity and composition in faecal microbial DNA. METHODS AND RESULTS:
      Participants (25 men and 26 women, aged 17-65 years) provided questionnaire data
      and multiple samples of one stool collected with two Polymedco and two Sarstedt
      devices preloaded with RNAlater. 16S rRNA genes in each faecal DNA aliquot were
      amplified, sequenced (Roche/454 Life Sciences) and assigned to taxa. Devices were
      compared for ease of use and reproducibility [intraclass correlation coefficient
      (ICC)] between duplicate aliquots on diversity and taxonomic assignment.
      Associations were tested by linear regression. Both collection devices were easy
      to use. Both alpha diversity (Shannon index) and beta diversity (UniFrac) were
      higher between than within duplicates (P <= 10(-8) ) and did not differ
      significantly by device (P >= 0.62). Reproducibility was good (ICC>=0.77) for
      alpha diversity and taxonomic assignment to the most abundant phyla, Firmicutes
      and Bacteroidetes (71.5% and 25.0% of sequences, respectively), but
      reproducibility was low (ICC<=0.48) for less abundant taxa. Alpha diversity was
      lower with nonantibiotic prescription medication (P = 0.02), with younger age (P
      = 0.03) and marginally with higher body mass index (P = 0.08). CONCLUSIONS: With
      sampling from various parts of a stool, both devices provided good
      reproducibility on overall microbial diversity and classification for the major
      phyla, but not for minor phyla. Implementation of these methods should provide
      insights into how broad microbial parameters, but not necessarily rare microbes,
      affect risk of various conditions.

PMID- 22385293
TI  - Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage
      renal disease in patients with diabetic nephropathy.
AB  - AIMS:   Diabetic nephropathy (DN) is the major cause for end-stage renal disease
      (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present.
      Results from published studies on the relationship between angiotensin-converting
      enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN
      patients are still conflicting. This meta-analysis was performed to evaluate the
      association between ACE I/D gene polymorphism and ESRD risk in DN patients.
      METHODS:   Association studies were identified from the databases of PubMed,
      Embase and Cochrane Library on 1 October 2011, and eligible investigations were
      identified and synthesized using the meta-analysis method. Results were expressed
      using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI)
      were also calculated. RESULTS:   Twelve studies reporting the relation between
      ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In
      overall populations, there was a notable association between D allele or DD
      genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11-1.56, P = 0.002; DD:
      OR = 1.67, 95% CI: 1.25-2.21, P = 0.0004). In the sub-group analysis according to
      ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In
      Caucasians, the association of DD genotype with ESRD risk was observed, but the D
      allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD
      risk in patients with DN due to diabetes mellitus type 2, but the association was
      not found for patients with DN due to diabetes mellitus type-1. CONCLUSIONS:  
      Our results indicate that D allele or DD homozygous is associated with the ESRD
      susceptibility in DN patients. However, more investigations are required to
      further this association.

PMID- 22385294
TI  - Gender-specific association of methylenetetrahydrofolate reductase gene
      polymorphisms with sporadic amyotrophic lateral sclerosis.
AB  - Studies have revealed that elevated homocysteine levels can cause damage to motor
      neurons through multiple neurotoxic mechanisms, thus leading to the pathogenesis
      of amyotrophic lateral sclerosis (ALS). One way by which homocysteine levels are
      increased in the body is the consequence of methylenetetrahydrofolate reductase
      (MTHFR) gene polymorphisms. Therefore, to address this question, we studied the
      MTHFR C677T and A1298C polymorphisms in 437 sporadic ALS (SALS) and 439 healthy
      controls to learn whether they were associated with SALS. The overall SALS were
      not associated with MTHFR C677T and A1298C polymorphisms (chi(2)=1.378; p=0.502;
      chi(2)=1.304; p=0.521, respectively). However, when we stratified results in
      terms of gender, we found that the MTHFR C677T polymorphism (chi(2)=6.376;
      p=0.041), T677T genotype (chi(2)=5.508; p=0.019; odds ratio [OR]=2.561; 95%
      confidence interval [CI]=1.142-5.744), C677C/A1298A (chi(2)=5.216; p=0.022;
      OR=0.424, 95% CI=0.199-0.900), and T677T/A1298A (chi(2)=6.639; p=0.010; OR=2.900;
      95% CI=1.252-6.717) compound genotypes were associated with SALS in female
      patients only. Moreover, stratification of SALS according to the onset of disease
      indicated that there was no association between MTHFR C677T (chi(2)=1.565;
      p=0.457; A1298C chi(2)=3.461; p=0.177) polymorphisms and overall spinal onset
      SALS. Further stratification analysis according to gender revealed that there was
      a remarkable association between MTHFR C677T (chi(2)=9.728, p=0.008), T677T
      genotype (chi(2)=7.820; p=0.005; OR=3.126; 95% CI=1.361-7.178) and T allele
      (chi(2)=5.000; p=0.025; OR=1.711; 95% CI=1.067-2.745), and T677T/A1298A compound
      genotype (chi(2)=9.108; p=0.003; OR=3.540; 95% CI=1.494-8.387) and spinal onset
      female SALS only. Likewise, there was also association between MTHFR A1298C
      polymorphism (chi(2)=5.946; p=0.051) and the C1298C genotype (chi(2)=5.282;
      p=0.022; OR=2.524; 95% CI=1.125-5.658), and the C677T/C1298C compound genotype
      (chi(2)=7.155; p=0.007; OR=1.045; 95% CI=0.983-1.112) and bulbar onset SALS only
      in women. In conclusion, the evidence we provide here clearly shows that MTHFR
      C677T and A1298C polymorphisms are genetic risk factors for SALS in women in a
      gender-specific manner whether they are of spinal or bulbar onset.

PMID- 22385296
TI  - Galactosylated nanostructured lipid carriers for delivery of 5-FU to
      hepatocellular carcinoma.
AB  - The aim of the present study was to design a targeted delivery system of 5
      fluorouracil (5-FU) for hepatocellular carcinoma (HCC). Lactobionic acid (LB) was
      conjugated to stearyl amine (SA) by a chemical reaction. The nanostructured lipid
      carriers (NLCs), containing LB conjugate, lecithin, glyceryl monostearate, oil
      [oleic acid (OA) or Labrafac 5 or 10%], and 5-FU, were dissolved in
      alcohol/acetone, the oil phase was added to the aqueous phase containing Tween 80
      or Solutol((r)) HS15 (0.25 or 0.5%), and NLCs were prepared by an emulsification
      solvent diffusion method. Physical properties and drug release were studied in
      NLCs. The thiazolyl blue tetrazolium bromide assay was used to study the
      cytotoxicity of NLCs on HepG(2) cells, and the cellular uptake of NLCs was
      determined by flow cytometry. Fourier transform infrared spectroscopy and (1)H
      NMR spectra confirmed the successful conjugation of LB and SA. The optimized NLCs
      consisted of 0.5% Solutol HS15 and 10% OA oil. The particle size of these
      nanoparticles was 139.2 nm, with a zeta potential of -18 mV, loading efficiency
      of 34.2%, release efficiency after 2 hours of the release test was 72.6%, and
      crystallinity was 0.63%. The galactosylated NLCs of 5-FU were cytotoxic on the
      HepG(2) cell line in a half concentration of 5-FU and seems promising in reducing
      5-FU dose in HCC.

PMID- 22385295
TI  - Proteolytic regulation of the mitochondrial cAMP-dependent protein kinase.
AB  - The mitochondrial cAMP-dependent protein kinase (PKA) is activatable in a cAMP
      independent fashion. The regulatory (R) subunits of the PKA holoenzyme
      (R(2)C(2)), but not the catalytic (C) subunits, suffer proteolysis upon exposure
      of bovine heart mitochondria to digitonin, Ca(2+), and a myriad of electron
      transport inhibitors. Selective loss of both the RI- and RII-type subunits was
      demonstrated via Western blot analysis, and activation of the C subunit was
      revealed by phosphorylation of a validated PKA peptide substrate. Selective
      proteolysis transpires in a calpain-dependent fashion as demonstrated by exposure
      of the R and C subunits of PKA to calpain and by attenuation of R and C subunit
      proteolysis in the presence of calpain inhibitor I. By contrast, exposure of
      mitochondria to cAMP fails to promote R subunit degradation, although it does
      result in enhanced C subunit catalytic activity. Treatment of mitochondria with
      electron transport chain inhibitors rotenone, antimycin A, sodium azide, and
      oligomycin, as well as an uncoupler of oxidative phosphorylation, also elicits
      enhanced C subunit activity. These results are consistent with the notion that
      signals, originating from cAMP-independent sources, elicit enhanced mitochondrial
      PKA activity.

PMID- 22385297
TI  - Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic
      subjects: marker or maker of the diabetic phenotype?
AB  - The diabetic phenotype is complex, requiring elucidation of key initiating
      defects. Recent research has shown that diabetic myotubes express a primary
      reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also
      been shown both in insulin resistant offspring of T2D patients and exercising T2D
      patients in vivo. This review will discuss the latest advances in the
      understanding of the molecular mechanisms regulating the TCA cycle with focus on
      possible underlying mechanism which could explain the impaired TCA flux in
      insulin resistant human skeletal muscle in type 2 diabetes. A reduced TCA is both
      a marker and a maker of the diabetic phenotype.

PMID- 22385298
TI  - Reply to "Vitamin D supplementation did not prevent influenza-like illness as
      diagnosed retrospectively by questionnaires in subjects participating in
      randomized clinical trials".

PMID- 22385299
TI  - Synthesis of fused indazole ring systems and application to nigeglanine
      hydrobromide.
AB  - The single-step synthesis of fused tricyclic pyridazino[1,2-a]indazolium ring
      systems is described. Structural details revealed by crystallography explain the
      unexpected reactivity. The method is applied to the gram scale synthesis of
      nigeglanine hydrobromide.

PMID- 22385301
TI  - Computer simulations of nucleation of nanoparticle superclusters from solution.
AB  - This paper presents simulation studies of nanoparticle supercluster (NPSC)
      nucleation from a temperature quenched system. The nanoparticles are represented
      as 5 nm, spherical gold nanoparticles ligated with alkane thiols. The pair
      potential accounts for the van der Waals interaction between the metallic cores
      and ligand-ligand and ligand-solvent interactions. Phenomena well-known for
      molecular systems are observed including a prenucleation induction period,
      fluctuating prenucleation clusters that predominately add monomers one at a time,
      a critical nucleus size, and growth of NPSCs from solution in the presence of an
      equilibrium supernatant, all consistent with classical nucleation theory.
      However, only the largest prenucleating clusters are dense, and the cluster size
      can occasionally range greater than the critical size in the prenucleation regime
      until a cluster with low enough energy occurs, then nucleation ensues. Late in
      the nucleation process, the clusters display a crystalline structure that is a
      random mix of face-centered cubic (fcc) and hexagonal close-packed (hcp) lattices
      and indistinguishable from a randomized icosahedra structure.

PMID- 22385300
TI  - A clinicopathological study of malignant odontogenic tumours.
AB  - AIMS: Malignant odontogenic tumours (MOTs) are rare neoplasms occurring primarily
      within the jaw. The objective of this study was to determine the incidence,
      demographics and clinicopathological features of the MOTs from two institutions.
      METHODS AND RESULTS: The records of the Department of Oral Pathology, Faculty of
      Dentistry, Chulalongkorn University, Bangkok, Thailand and the Department of
      Oncology and Diagnostic Sciences, Dental School, University of Maryland,
      Baltimore, USA were searched from 1991 to 2010; we identified 17 cases of
      previously diagnosed MOTs. All cases were reviewed independently of the previous
      diagnosis by two blinded oral pathologists and reclassified based on the 2005
      World Health Organization classification of head and neck tumours. In this study
      we describe in detail these 17 cases which presented with an average age of 50.29
      years and a male to female ratio of 2.4:1. These cases included five ameloblastic
      carcinomas, four atypical ameloblastomas, three primary intraosseous squamous
      cell carcinomas, three intraosseous mucoepidermoid carcinomas and two clear cell
      odontogenic carcinomas. All cases were treated by surgical resection and one
      patient with ameloblastic carcinoma received postoperative radiotherapy.
      CONCLUSIONS: Malignant odontogenic tumours are considered rare central
      odontogenic lesions. Awareness of their existence, rapid diagnosis and successful
      treatment using surgery, radiation and/or chemotherapy is critical to patient
      survival.

PMID- 22385302
TI  - Rapid inactivation of biological species in the air using atmospheric pressure
      nonthermal plasma.
AB  - Here, nonthermal plasma generated by a dielectric barrier discharge (DBD) system
      was applied to inactivating aerosolized Bacillus subtilis cells and Pseudomonas
      fluorescens as well as indoor and outdoor bioaerosols. The culturability,
      viability, and diversity losses of the microorganisms in air samples treated by
      the plasma for 0.06-0.12 s were studied using culturing, DNA stain as well as
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      methods. In addition, the viable fraction of bacterial aerosols with and without
      the plasma treatment was also quantified using qPCR coupled with ethidium
      monoazide (EMA). It was shown that less than 2% of B. subtilis aerosols survived
      the plasma treatment of 0.12 s, while none of the P. fluorescens aerosols
      survived. Viability tests, EMA-qPCR results, and Scanning Electron Microscopy
      (SEM) images demonstrated that both bacterial species suffered significant
      viability loss, membrane, and DNA damages. Exposure of environmental bacterial
      and fungal aerosols to the plasma for 0.06 s also resulted in their significant
      inactivations, more than 95% for bacteria and 85-98% for fungal species. PCR-DGGE
      analysis showed that plasma exposure of 0.06 s resulted in culturable bacterial
      aerosol diversity loss for both environments, especially pronounced for indoor
      environment. The results here demonstrate that nonthermal plasma exposure could
      offer a highly efficient air decontamination technology.

PMID- 22385303
TI  - Personal cooling with phase change materials to improve thermal comfort from a
      heat wave perspective.
AB  - The impact of heat waves arising from climate change on human health is predicted
      to be profound. It is important to be prepared with various preventive measures
      for such impacts on society. The objective of this study was to investigate
      whether personal cooling with phase change materials (PCM) could improve thermal
      comfort in simulated office work at 34 degrees C. Cooling vests with PCM were
      measured on a thermal manikin before studies on human subjects. Eight male
      subjects participated in the study in a climatic chamber (T(a) = 34 degrees C, RH
      = 60%, and nu(a) = 0.4 m/s). Results showed that the cooling effect on the
      manikin torso was 29.1 W/m(2) in the isothermal condition. The results on the
      manikin using a constant heating power mode reflect directly the local cooling
      effect on subjects. The results on the subjects showed that the torso skin
      temperature decreased by about 2-3 degrees C and remained at 33.3 degrees C. Both
      whole body and torso thermal sensations were improved. The findings indicate that
      the personal cooling with PCM can be used as an option to improve thermal comfort
      for office workers without air conditioning and may be used for vulnerable
      groups, such as elderly people, when confronted with heat waves. PRACTICAL
      IMPLICATIONS: Wearable personal cooling integrated with phase change materials
      has the advantage of cooling human body's micro-environment in contrast to
      stationary personalized cooling and entire room or building cooling, thus
      providing greater mobility and helping to save energy. In places where air
      conditioning is not usually used, this personal cooling method can be used as a
      preventive measure when confronted with heat waves for office workers, vulnerable
      populations such as the elderly and disabled people, people with chronic
      diseases, and for use at home.

PMID- 22385304
TI  - Biologically relevant lyotropic liquid crystalline phases in mixtures of n-octyl
      beta-D-glucoside and water. Determination of the phase diagram by fluorescence
      spectroscopy.
AB  - When mixed with water, n-octyl beta-D-glucoside forms self-assembled
      nanostructures, several of which are liquid crystalline and all of which depend
      on the water/glucoside ratio and temperature. For practical use of these phases,
      a detailed understanding of the conditions under which they exist (i.e., the
      isobaric phase diagram) is required. We use the fluorescence of the dye molecule
      prodan as a new approach to probe the phases formed in these mixtures. The prodan
      fluorescence signal depends on the polarity of its environment and thus the
      phase(s) in which the dye exists. Visual inspection of the total fluorescence
      signal can qualitatively determine the phases present, including coexisting
      phases. Temperature-induced phase changes are also detected from variations
      observed in the prodan fluorescence spectrum. The sensitivity of this new
      technique allows the single- and multiple-phase regions to be mapped carefully
      for the first time.

PMID- 22385305
TI  - Separation of soybean isoflavone aglycone homologues by ionic liquid-based
      extraction.
AB  - The separation of a compound of interest from its structurally similar homologues
      is an important and challenging problem in producing high-purity natural
      products, such as the separation of genistein from other soybean isoflavone
      aglycone (SIA) homologues. The present work provided a novel method for
      separating genistein from its structurally similar homologues by ionic liquid
      (IL)-based liquid-liquid extraction using hydrophobic IL-water or hydrophilic
      IL/water-ethyl acetate biphasic systems. Factors that influence the distribution
      equilibrium of SIAs, including the structure and concentration of IL, pH value of
      the aqueous phase, and temperature, were investigated. Adequate distribution
      coefficients and selectivities over 7.0 were achieved with hydrophilic IL/water
      ethyl acetate biphasic system. Through a laboratory-scale simulation of
      fractional extraction process containing four extraction stages and four
      scrubbing stages, genistein was separated from the SIA homologues with a purity
      of 95.3% and a recovery >90%.

PMID- 22385306
TI  - Accurate thermochemistry of hydrocarbon radicals via an extended generalized bond
      separation reaction scheme.
AB  - Detailed knowledge of hydrocarbon radical thermochemistry is critical for
      understanding diverse chemical phenomena, ranging from combustion processes to
      organic reaction mechanisms. Unfortunately, experimental thermochemical data for
      many radical species tend to have large errors or are lacking entirely. Here we
      develop procedures for deriving high-quality thermochemical data for hydrocarbon
      radicals by extending Wheeler et al.'s "generalized bond separation reaction"
      (GBSR) scheme (J. Am. Chem. Soc., 2009, 131, 2547). Moreover, we show that the
      existing definition of hyperhomodesmotic reactions is flawed. This is because
      transformation reactions, in which one molecule each from the predefined sets of
      products and reactants can be converted to a different product and reactant
      molecule, are currently allowed. This problem is corrected via a refined
      definition of hyperhomodesmotic reactions in which there are equal numbers of
      carbon-carbon bond types inclusive of carbon hybridization and number of
      hydrogens attached. Ab initio and density functional theory (DFT) computations
      using the expanded GBSRs are applied to a newly derived test set of 27
      hydrocarbon radicals (HCR27). Greatly reduced errors in computed reaction
      enthalpies are seen for hyperhomodesmotic and other highly balanced reactions
      classes, which benefit from increased matching of hybridization and bonding
      requirements. The best performing DFT methods for hyperhomodesmotic reactions,
      M06-2X and B97-dDsC, give average deviations from benchmark computations of only
      0.31 and 0.44 (+/-0.90 and +/-1.56 at the 95% confidence level) kcal/mol,
      respectively, over the test set. By exploiting the high degree of error
      cancellation provided by hyperhomodesmotic reactions, accurate thermochemical
      data for hydrocarbon radicals (e.g., enthalpies of formation) can be computed
      using relatively inexpensive computational methods.

PMID- 22385307
TI  - An alternative approach for augmenting the anterior maxilla using autogenous free
      gingival bone graft for implant retained prosthesis.
AB  - Abstract   Numerous factors may refrain surgeons from placing implants in the
      anterior maxilla in order to avoid suboptimal restorative outcomes. This paper
      describes a technique of an autogenous free gingival- bone block graft, which
      allows bone and gingival augmentation and a primary seal to be achieved
      simultaneously. Additionally, it describes a technique for achieving primary soft
      tissue closure of maxillary extraction sockets using a rotated pedicle palatal
      connective tissue flap.

PMID- 22385308
TI  - Attachment representations and response to video-feedback intervention for
      professional caregivers.
AB  - Interventions to improve caregiving may have different effects for persons with
      autonomous or nonautonomous attachment representations. The current study used
      the Adult Attachment Interview to investigate attachment representations of
      professional caregivers who participated in an intervention to improve
      interaction with children and adults with serious intellectual and visual
      disabilities. Caregivers (N = 51) completed a video-feedback interaction program.
      Twice during a baseline period and three times during the intervention period,
      each caregiver was videotaped during a standard situation with their client. Of
      the caregivers, 28 were classified as autonomous, 12 as dismissing, and 11 as
      preoccupied. Unresolved loss or trauma (n = 7) was not included in the analyses.
      Generally, interaction quality improved from baseline to intervention period as
      indicated by confirmation of signals, responsiveness to signals, and affective
      mutuality. Caregivers with dismissing classifications continued to show less
      confirmation of clients' signals. Caregivers with dismissing or preoccupied
      classifications improved their responsiveness to the level of caregivers with
      autonomous classifications. Attachment representations may modify in some ways
      the impact of interventions to improve caregiving.

PMID- 22385309
TI  - Maternal sensitivity to infants in various settings predicts harsh discipline in
      toddlerhood.
AB  - In a longitudinal study with 73 mothers and their second-born child, stability
      and main-level differences between measures of maternal sensitivity across
      settings and over time were examined. Furthermore, the predictability of harsh
      discipline by these different maternal sensitivity measures was studied. Maternal
      sensitivity was assessed at three and six months during bathing, free play on
      mother's lap and the baseline and reunion episode of the Still Face Paradigm
      (SFP; Tronick, Als, Adamson, Wise, & Brazelton,  1978 ). Harsh discipline was
      observed during three home visits in the second year of life. Results showed a
      single underlying factor for all maternal sensitivity settings at both time
      points and significant stability over time. Harsh discipline was predicted by
      maternal sensitivity at three months, which was fully mediated by maternal
      sensitivity at six months. Early failure to respond appropriately to infant
      signals is an important indicator of risk for future harsh parenting.

PMID- 22385310
TI  - The reporting of maltreatment experiences during the Adult Attachment Interview
      in a sample of pregnant adolescents.
AB  - This present student examines maltreatment experiences reported by 55 high-risk
      pregnant adolescents in response to a slightly adapted version of the Adult
      Attachment Interview (AAI; George, Kaplan, & Main,  1996 ). Previous research has
      suggested that the rates of unresolved states of mind regarding trauma in
      response to the AAI may be underestimated due to the lack of direct questions and
      associated probes regarding physical, sexual, and emotional abuse. We address
      this concern by including behaviorally phrased questions and probes regarding
      maltreatment experiences into the original format of the AAI and examine the
      concordance between reports of maltreatment experiences in response to the AAI
      and the Childhood Trauma Questionnaire (CTQ). Maltreatment experiences in
      response to the AAI were evaluated using the Maltreatment Classification Scale
      developed by Barnett, Manly, and Cicchetti (1993). We also examine the
      association between unresolved states of mind and dissociation using the
      Adolescent Dissociative Experience Scale. Results revealed a significant
      concordance between reports of maltreatment in response to the AAI and CTQ
      measures. Reports of maltreatment were prevalent in this sample: across the AAI
      and CTQ measures, 96% of pregnant adolescents reported some form of emotional
      abuse, 84% physical abuse, 59% sexual abuse, and 88% reported neglect. Sexual
      abuse history uniquely predicted unresolved status in response to the AAI. Self
      reports of dissociation were significantly associated with unresolved states of
      mind. Results suggest that the inclusion of behaviorally focused questions and
      probes regarding maltreatment in the AAI protocol can further contribute to the
      clinical and theoretical value of this tool.

PMID- 22385311
TI  - Dissociation and the Adult Attachment Interview in artists and performing
      artists.
AB  - Attachment patterns were investigated in a group of professional and pre
      professional artists (n = 51). Given the high level of absorption/imagination
      required of artists, this study examined normative and pathological dissociation
      (PD) and considered links with Adult Attachment Interview responses, with
      particular attention to the AAI classification Unresolved (U) for past loss or
      trauma. Results indicated: (1) artists had elevated mean scores for
      absorption/imagination, (2) all but one artist had adverse trauma or loss
      experiences, (3) 17 (36%) met criteria for PD and 9 (53%) of those in the PD
      range had a classification of Unresolved (U) on the Adult Attachment Interview
      (AAI), (4) U was associated with PD, but not normative dissociation
      (absorption/imagination), (5) even with a primary U classification many
      individuals had an alternate secure/autonomous classification, and (6) 88% of the
      artists were classified as secure/autonomous in a three-way analysis on the AAI,
      but in a four-way analysis 27.5% were classified as U. Although 36% presented
      with PD, the majority of artists studied were stable, coherent and autonomous.

PMID- 22385312
TI  - The family drawings of at-risk children: concurrent relations with contact with
      incarcerated parents, caregiver behavior, and stress.
AB  - The current study examined children's attachment representations as assessed with
      their family drawings in relation to contact with an incarcerated or estranged
      parent, caregiver behavior, and family stress in a high-risk sample of children
      (N = 44, M (age) = 8.14), 55% of whom had incarcerated parents. Greater phone,
      mail, and physical contact with an incarcerated parent was associated with more
      role reversal in children's family drawings. Additional results show that child
      reports of more hostile caregiver behavior were associated with greater overall
      insecurity in their family drawings; child and caregiver reports of stress were
      associated with increased global pathology and bizarreness/dissociation in
      children's family drawings. Given the lack of research on concurrent familial
      based correlates of ratings made of children's family drawings, these results
      provide additional insights into children's representations of attachment
      relationships in early middle childhood. Further, the results regarding contact
      with incarcerated parents have implications for researchers and clinicians
      working with families impacted by parental incarceration.

PMID- 22385313
TI  - The mother and the motherland: their internal representations among immigrant and
      non-immigrant adolescents.
AB  - This paper studies associations between internal representations that adolescents
      hold for their mothers and internal representations of the country they belong
      to, and the extent to which such internal representations impact on psychological
      adjustment. Two studies were conducted: the first with 328 Russian adolescents in
      Russia, and the second with 178 Jewish adolescent immigrants from Russia in
      Israel. In both samples, representations of the mother as caring were
      significantly related to the adolescents' positive attitudes towards their
      country of living. In addition, the adolescents' positive attitudes towards
      country of living were significantly related to their psychological adjustment,
      over and above internal representations of mother. Findings suggest the
      importance of theories of internal representations for understanding the dynamics
      of the adolescents' attachment to social objects and their psychological
      adjustment.

PMID- 22385314
TI  - HLA alloimmunization against platelet transfusions: pathophysiology,
      significance, prevention and management.
AB  - Approximately five decades ago, alloimmunization to human leukocyte antigens
      (HLA) and platelet refractoriness were recognized as potentially serious
      complications of platelet transfusions. The mechanisms that result in stimulating
      immunity against blood products are still incompletely understood but are related
      to both the composition of the donor product transfused and the immune status of
      the recipient. Based on murine studies of platelet immunity, platelets are
      inherently immunogenic and there are at least two independent levels of
      immunoregulation against platelet transfusions. The first level resides within
      the recipient and is related to antigen processing/presentation events and CD8+ T
      cell-mediated immunosuppression. The second level relates to the donor product
      and includes donor antigen presenting cells (APC) levels as well as age-induced
      changes in donor APC and/or platelets. Implementation of pre-storage
      leukoreduction of cellular blood components led to a marked reduction in platelet
      alloimmunization and its dreaded complication, platelet refractoriness. Platelet
      refractoriness is usually managed by transfusion of matched platelets, selected
      according to one of the many published methods. It is unclear which of these
      methods is superior, and given the difficulty of obtaining a perfectly matched
      product, perhaps the most logical approach is to use a combination of selection
      strategies. This review discusses the various aspects of platelet
      alloimmunization and the clinical consequences that may result. It highlights how
      animal studies have shed light on the immune mechanisms responsible for
      allogeneic platelet immunity and immunomodulation and reviews relevant literature
      on clinical and laboratory manifestations of immune platelet refractoriness.

PMID- 22385316
TI  - Drug delivery in multiple indication (multipurpose) prevention technologies:
      systems to prevent HIV-1 transmission and unintended pregnancies or HSV-2
      transmission.
AB  - INTRODUCTION: The development of multiple indication (multipurpose) prevention
      technologies (MIPTs) is driven by overlapping relationships in the area of female
      reproductive health. AREAS COVERED: In this review, the basis for MIPTs is
      detailed. The current state of the field for the use of drug delivery in novel
      MIPTs is covered. Of particular interest is the application of intravaginal rings
      (IVRs) for the delivery of two drugs simultaneously, to prevent one STI and
      pregnancy, or two STIs. IVRs are currently available commercially for
      contraception and have been developed for release of microbicides to prevent
      sexual transmission of HIV-1. Novel IVRs capable of releasing relatively large
      amounts of drugs such as tenofovir are discussed, along with those that contain
      independent delivery elements, such as pods, that can be used to release drugs at
      independent rates. The vaginal administration of macromolecules (antibodies and
      vaccines) is also reviewed in the context of MIPTs. EXPERT OPINION: The field of
      MIPTs remains one of potential. There is yet to be a proven microbicide effective
      at preventing sexual transmission of HIV-1. Development of MIPTs in the near term
      will proceed under the assumption that one or more antiretroviral (ARV) drugs
      will eventually be proven successful. IVRs have already demonstrated success in
      the area of contraception. Prevention of sexual transmission of HIV-1 and herpes
      simplex virus-2 (HSV-2) (or suppression of recurrence) remains an attractive MIPT
      target. In the long term, development of MIPTs will require validation of
      surrogate end points, particularly for prevention of HIV-1 transmission.

PMID- 22385317
TI  - Comparative microbial ecology study of the sediments and the water column of the
      Rio Tinto, an extreme acidic environment.
AB  - Due to its highly metalliferous waters and low pH, the Rio Tinto has shown its
      potential for modelling both acid mine drainage systems and biohydrometallurgical
      operations. Most geomicrobiological studies of these systems have focused on the
      oxic water column. A sequence-based approach in combination with in situ
      detection techniques enabled us to examine the composition and structure of the
      microbial communities associated with the suboxic and anoxic sediments along the
      river course and to compare them with the planktonic communities inhabiting the
      water column. The results obtained with the different approaches were consistent
      and revealed some major patterns: higher cell density and higher richness (75 vs.
      48 operational taxonomic units) in the sediments than in the water column. The
      microbial communities were related but the river sediments appear to be enriched
      in certain populations, some of which have not previously been reported in the
      Rio Tinto basin. The differences detected between sampling stations along the
      river correlate with certain environmental parameters (e.g. iron concentration
      gradient). The biological and geochemical data show the importance of the
      sediments as representing a phase of particular high diversity, probably related
      to key metabolic processes within both the iron and the sulfur cycles.

PMID- 22385318
TI  - Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ
      1 expression at mRNA and protein levels in ductal carcinoma of the breast.
AB  - AIMS: DJ-1 is a molecule secreted into serum by some breast cancer cells.
      However, little is known about the clinical significance of the DJ-1 expression.
      METHODS AND RESULTS: Expression of DJ-1 protein was examined by
      immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ
      hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas
      in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast
      cancer cells were examined for their secretion of DJ-1 using immunoblot analysis.
      By immunohistochemistry DJ-1 protein expression was lower than adjacent non
      cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs,
      even although all 314 carcinomas retained expression of DJ-1 mRNA, which was
      higher than that in adjacent non-cancerous epithelium in 220 cases (70%).
      Patients with IDC whose cancer cells showed low expression of DJ-1 protein had
      significantly shorter disease-free survival (P = 0.0152) and overall survival (P
      = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231
      cells, which secreted DJ-1, showed low expression of DJ-1 protein. CONCLUSIONS:
      Low expression of DJ-1 protein with high expression of its mRNA, which may
      reflect a secretory expression pattern, is predictive of poor outcome in patients
      with IDC.

PMID- 22385319
TI  - Alkaline extracellular reduction: isolation and characterization of an
      alkaliphilic and halotolerant bacterium, Bacillus pseudofirmus MC02.
AB  - AIMS: To isolate an alkaliphilic bacterium and to investigate its ability of
      extracellular reduction. METHODS AND RESULTS: An alkaliphilic and halotolerant
      humus-reducing anaerobe, Bacillus pseudofirmus MC02, was successfully isolated
      from a pH 10.0 microbial fuel cell. To examine its ability of extracellular
      reduction, AQDS (anthraquinone-2, 6-disulfonae), humic acids (HA) and Fe(III)
      oxides were chosen as representative electron acceptors. All the experiments were
      conducted in a pH 9.5 carbonate buffer. The results are as follows: (i) Sucrose,
      lactate, glucose and glycerol were the favourable electron donors for AQDS
      reduction by the strain MC02; (ii) The strain had the ability of reducing HA in
      the presence of sucrose; (iii) It could effectively reduce Fe(III) oxides coupled
      with sucrose fermentation when AQDS was added as electron shuttle and its Fe(III)
      reducing capacity ranked as: lepidocrocite (gamma-FeOOH) > goethite (alpha-FeOOH)
      > haematite(alpha-Fe(2) O(3) ); (iv) The strain could decolourize azo dye Orange
      I. CONCLUSIONS: Bacillus pseudofirmus MC02 was capable of extracellular reduction
      in AQDS, HA and Fe(III) oxides, and it can be used for decolourizing azo dye
      (Orange I) in alkaline conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This is
      the first report of an alkaliphlic strain of B. pseudofirmus capable of
      extracellular reduction in AQDS, HA, Fe(III) oxides and decolourization of Orange
      I. This study could provide valuable information on alkaline biotransformation in
      the printing and dyeing wastewater and saline-alkali soil.

PMID- 22385320
TI  - Analysis of antimicrobial resistance genes detected in multiple-drug-resistant
      Escherichia coli isolates from broiler chicken carcasses.
AB  - Multi-drug-resistant (MDR) bacteria in food animals are a potential problem in
      both animal and human health. In this study, MDR commensal Escherichia coli
      isolates from poultry were examined. Thirty-two E. coli isolates from broiler
      carcass rinses were selected based on their resistance to aminoglycosides, beta
      lactams, chloramphenicols, tetracyclines, and sulfonamide antimicrobials.
      Microarray analysis for the presence of antimicrobial resistance and plasmid
      genes identified aminoglycoside [aac(6), aac(3), aadA, aph, strA, and strB], beta
      lactam (bla(AmpC), bla(TEM), bla(CMY), and bla(PSE-1)), chloramphenicol (cat,
      flo, and cmlA), sulfamethoxazole (sulI and sulII), tetracycline [tet(A), tet(C),
      tet(D), and tetR], and trimethoprim (dfrA) resistance genes. IncA/C plasmid core
      genes were detected in 27 isolates, while IncHI1 plasmid genes were detected in
      one isolate, indicating the likely presence of these plasmids. PCR assays for 18
      plasmid replicon types often associated with MDR in Enterobacteriaceae also
      detected one or more replicon types in all 32 isolates. Class I integrons were
      investigated by PCR amplification of the integrase I gene, intI1, and the
      cassette region flanked by conserved sequences. Twenty-five isolates were
      positive for the intI1 gene, and class I integrons ranging in size from ~1,000 to
      3,300 bp were identified in 19 of them. The presence of class I integrons, IncA/C
      plasmid genes, and MDR-associated plasmid replicons in the isolates indicates the
      importance of these genetic elements in the accumulation and potential spread of
      antimicrobial resistance genes in the microbial community associated with
      poultry.

PMID- 22385321
TI  - Decreased serum linezolid concentrations in two patients receiving linezolid and
      rifampicin due to bone infections.
AB  - Methicillin-resistant Staphylococcus is a common cause of orthopaedic implant
      infections. In such cases, rifampicin is the antibiotic of choice, but it should
      not be administered alone to avoid the selection of resistant mutants. Linezolid
      has activity against resistant staphylococci and a high oral bioavailability;
      therefore, it could be a good option for combining with rifampicin. We describe 2
      patients admitted to our hospital due to orthopaedic implant infections, who
      received combination therapy with linezolid and rifampicin. In both cases, the
      trough serum concentration of linezolid during rifampicin treatment was below the
      minimum inhibitory concentration required to inhibit the growth of 90% of
      organisms (MIC(90)) for staphylococci, but increased after rifampicin withdrawal.
      This finding suggests an interaction between rifampicin and linezolid, and a
      possible explanation is discussed.

PMID- 22385322
TI  - Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the
      treatment of climacteric complaints: a systematic review.
AB  - OBJECTIVE: The systematic review examines whether Cimicifuga racemosa (CR),
      Hypericum perforatum (HP), Agnus castus, vitamins and minerals, either as
      monotherapy or in combination, have an evidence-based impact on vasomotor,
      genital and psychological climacteric complaints. DATA SOURCES AND METHODS OF
      STUDY SELECTION: We searched in the databases EMBASE, OVID and PubMed using the
      keywords "vasomotor symptoms, hot flashes, vaginal atrophy, psychological
      problems, endometrium, sleep, concentration, cognition in combination with
      vitamins, multivitamins, minerals, multiminerals, black cohosh, Cimicifuga, Agnus
      castus, chasteberry, chaste tree, monk's pepper and menopause" for randomized
      controlled trials (RCT). Relevant studies were reviewed by four independent
      reviewers qualitatively. RESULTS: Most of the studies with a comparison of CR vs.
      placebo do not show an evidence-based significant effect of CR on climacteric
      symptoms. The combination of CR and HP shows an improvement of climacteric
      complaints in comparison to placebo. In some RCTs, there was no significant
      difference between CR and hormone-replacement therapy. The combination of HP and
      Agnus castus showed no significant difference in the treatment of climacteric
      complaints. CONCLUSION: CR monotherapy as well as HP and Agnus castus showed no
      better effect than placebo. The combination of CR with HP demonstrated a positive
      effect on climacteric complaints.

PMID- 22385323
TI  - Concentration of free vascular endothelial growth factor and its soluble
      receptor, sFlt-1 in the maternal and fetal circulations of normal term
      pregnancies at high and low altitudes.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is regulated by hypoxia that
      is essential for placental development. It is antagonized by a soluble form of
      its receptor (sFlt-1). The purpose of this study was to measure these factors in
      the maternal and the cord bloods, at low and high altitude. METHODS: Samples were
      collected from full term births normal pregnant women. Free (unbound) VEGF and
      sFlt-1 levels were measured in plasma samples from cord and maternal blood for
      each subject by enzyme-linked immunosorbent assay (ELISA) using commercially
      available kits from R&D systems, UK (Cat # DVE00 and Cat # SVR100B,
      respectively). RESULTS: At high altitude, the average maternal free VEGF in pg/ml
      was significantly (p < 0.001) lower than that of the cord level (71.30 +/- 282.14
      and 431.35 +/- 424.31, respectively). On the other hand, the average maternal
      sFlt-1 was significantly (p < 0.001) higher than that of the cord level (8205.41
      +/- 6244.72 and 1811.74 + 3469.30, respectively). At low altitude, the average
      maternal free VEGF was significantly lower than that of the cord level (0.47 +/-
      0.89 and 483.44 +/- 457.31, respectively, p < 0.001). On the other hand, the
      average maternal sFlt-1 was significantly higher than that of the cord level
      (9267.82 +/- 6345.68 and 958.66 +/- 1359.92, respectively, p < 0.001). There were
      no significant differences by altitude. CONCLUSION: Secretion of sFlt-1 appears
      to be polarized, in that concentrations are higher in the maternal compartment
      than on the fetal side at both high and low altitudes. This may be a normal
      physiological phenomenon to permit angiogenesis in the placenta and fetus while
      protecting the mother. Chronic exposure to hypobaric hypoxia at high altitude
      does not affect these distributions.

PMID- 22385324
TI  - An early investigation of ytterbium nanocolloids for selective and quantitative
      "multicolor" spectral CT imaging.
AB  - We report a novel molecular imaging agent based on ytterbium designed for use
      with spectral "multicolor" computed tomography (CT). Spectral CT or multicolored
      CT provides all of the benefits of traditional CT, such as rapid tomographic X
      ray imaging, but in addition, it simultaneously discriminates metal-rich contrast
      agents based on the element's unique X-ray K-edge energy signature. Our synthetic
      approach involved the use of organically soluble Yb(III) complex to produce
      nanocolloids of Yb of noncrystalline nature incorporating a high density of Yb
      (>500K/nanoparticle) into a stable metal particle. The resultant particles are
      constrained to vasculature (~200 nm) and are highly selective for binding fibrin
      in the ruptured atherosclerotic plaque. Nanoparticles exhibited excellent signal
      sensitivity, and the spectral CT technique uniquely discriminates the K-edge
      signal (60 keV) of Yb from calcium (bones). Bioelimination and preliminary
      biodistribution reflected the overall safety and defined clearance of these
      particles in a rodent model.

PMID- 22385325
TI  - Charge-transfer properties of lateral triphenylamine-dithienophosphole diads.
AB  - Installation of an exocyclic triphenylamine group at the phosphorus center
      provides access to dithienophosphole materials with lateral charge-transfer (CT)
      ability. The degree of CT can be significantly manipulated not only via oxidation
      of the P-center but also surprisingly by alkylation of the 2,6-position of the
      scaffold.

PMID- 22385328
TI  - Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted
      DNA delivery system.
AB  - The main objective of this study was to evaluate macrophage-targeted alginate
      nanoparticles as a noncondensing gene delivery system for potential anti
      inflammatory therapy. An external gelation method was employed to form plasmid
      DNA-encapsulated alginate nanoparticles. The nanoparticle surface was modified
      with a peptide sequence containing tuftsin (TKPR), and transfection efficiency
      was determined in J774A.1 macrophages. The effect of transfected mIL-10 in
      blocking expression of tumor necrosis factor-alpha (TNF-alpha) was evaluated in
      lipopolysaccharide (LPS)-stimulated cells. Scrambled peptide- and tuftsin
      modified cross-linked alginate nanoparticles efficiently encapsulated plasmid DNA
      and protected against DNase I degradation. The transgene expression efficiencies,
      measured using GFP and mIL-10 expressing plasmid DNA, were highest with tuftsin
      modified nanoparticles. Levels of TNF-alpha were significantly lower (p < 0.0001)
      in LPS-stimulated cells that were transfected with mIL-10 using alginate
      nanoparticles. The results of the study show that noncondensing alginate
      nanoparticles can efficiently deliver plasmid DNA, leading to sustained in vitro
      gene expression in macrophages.

PMID- 22385329
TI  - Plasmoelectronics: coupling plasmonic excitation with electron flow.
AB  - Explorations of the coupling of light and charge via localized surface plasmons
      have led to the discovery that plasmonic excitation can influence macroscopic
      flows of charge and, conversely, that charging events can change the plasmonic
      excitation. We discuss recent theory and experiments in the emerging field of
      plasmoelectronics, with particular emphasis on the application of these materials
      to challenges in nanotechnology, energy use, and sensing.

PMID- 22385330
TI  - Faster fermentation of cooked carrot cell clusters compared to cell wall
      fragments in vitro by porcine feces.
AB  - Plant cell walls are the major structural component of fruits and vegetables,
      which break down to cell wall particles during ingestion (oral mastication) or
      food processing. The major health-promoting effect of cell walls occurs when they
      reach the colon and are fermented by the gut microbiota. In this study, the
      fermentation kinetics of carrot cell wall particle dispersions with different
      particle size and microstructure were investigated in vitro using porcine feces.
      The cumulative gas production and short-chain fatty acids (SCFAs) produced were
      measured at time intervals up to 48 h. The results show that larger cell clusters
      with an average particle size (d(0.5)) of 298 and 137 MUm were more rapidly
      fermented and produced more SCFAs and gas than smaller single cells (75 MUm) or
      cell fragments (50 MUm), particularly between 8 and 20 h. Confocal microscopy
      suggests that the junctions between cells provides an environment that promotes
      bacterial growth, outweighing the greater specific surface area of smaller
      particles as a driver for more rapid fermentation. The study demonstrates that it
      may be possible, by controlling the size of cell wall particles, to design plant
      based foods for fiber delivery and promotion of colon fermentation to maximize
      the potential for human health.

PMID- 22385331
TI  - Managing research evidence to inform action: influencing HIV policy to protect
      marginalised populations in Pakistan.
AB  - Abstract   Our aim was to demonstrate that an understanding of the process of how
      research may (or may not) influence policy and practice is crucial to leverage
      research findings and bring about evidence-informed policy and its
      implementation. We describe a process of research design and execution, based on
      theories of the relationship between evidence and public policy-making, which
      sought to improve the uptake of evidence into the HIV policy-making process in
      Pakistan. We designed and implemented specific strategies in research methods,
      management and dissemination to increase the policy influence by recommendations
      from a multi-disciplinary research project. Research to policy is complex, rarely
      linear and causal attribution is problematic. Nonetheless, we believe that, in
      part, some of the current changes in HIV policy and practice in Pakistan may be
      due to the managed process of research influence. We offer four key
      recommendations for those concerned with improving the chances of seeing their
      research incorporated into policy and practice - these are (1) involve
      stakeholders in research management; (2) set realistic expectations of research
      impact; (3) invest in long-term research-policy-maker relationships; and (4)
      build capacity of end users to use research to demand policy change.

PMID- 22385332
TI  - Salicylimine-based fluorescent chemosensor for aluminum ions and application to
      bioimaging.
AB  - In this study, an assay to quantify the presence of aluminum ions using a
      salicylimine-based receptor was developed utilizing turn-on fluorescence
      enhancement. Upon treatment with aluminum ions, the fluorescence of the sensor
      was enhanced at 510 nm due to formation of a 1:1 complex between the chemosensor
      and the aluminum ions at room temperature. As the concentration of Al(3+) was
      increased, the fluorescence gradually increased. Other metal ions, such as Na(+),
      Ag(+), K(+), Ca(2+), Mg(2+), Hg(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+),
      Cd(2+), Pb(2+), Cr(3+), Fe(3+), and In(3+), had no such significant effect on the
      fluorescence. In addition, we show that the probe could be used to map
      intracellular Al(3+) distribution in live cells by confocal microscopy.

PMID- 22385333
TI  - A self-developed and constructed robot for minimally invasive cochlear
      implantation.
AB  - CONCLUSION: A robot built specifically for stereotactic cochlear implantation
      provides equal or better accuracy levels together with a better integration into
      a clinical environment, when compared with existing approaches based on
      industrial robots. OBJECTIVES: To evaluate the technical accuracy of a robotic
      system developed specifically for lateral skull base surgery in an experimental
      set-up reflecting the intended clinical application. The invasiveness of cochlear
      electrode implantation procedures may be reduced by replacing the traditional
      mastoidectomy with a small tunnel slightly larger in diameter than the electrode
      itself. METHODS: The end-to-end accuracy of the robot system and associated image
      guided procedure was evaluated on 15 temporal bones of whole head cadaver
      specimens. The main components of the procedure were as follows: reference screw
      placement, cone beam CT scan, computer-aided planning, pair-point matching of the
      surgical plan, robotic drilling of the direct access tunnel, and postoperative
      cone beam CT scan for accuracy assessment. RESULTS: The mean accuracy at the
      target point (round window) was 0.56 +/- 0.41 mm with an angular misalignment of
      0.88 +/- 0.40 degrees . The procedural time for the registration process through
      the completion of the drilling procedure was 25 +/- 11 min. The robot was fully
      operational in a clinical environment.

PMID- 22385334
TI  - PIM1 kinase as a target for cancer therapy.
AB  - INTRODUCTION: Inhibition of protein kinases has become a standard of modern
      clinical oncology. PIM1 belongs to a novel class of serine/threonine kinases with
      distinct molecular and biochemical features regulating various oncogenic
      pathways, for example hypoxia response, cell cycle progression and apoptosis
      resistance. PIM1 is overexpressed in human cancer diseases and has been
      associated with metastasis and overall treatment response; in experimental
      models, inhibition of PIM1 suppressed cell proliferation and migration, induced
      apoptotic cell death and synergized with other chemotherapeutic agents. AREAS
      COVERED: A PubMed literature search was performed to review the currently
      available data on PIM1 expression, regulation and targets; its implication in
      different types of cancer and its impact on prognosis are described. We present
      ATP-competitive PIM1 inhibitors and the state of the art of PIM1 inhibitor
      design. Finally, we highlight the development of the unusual class of highly
      selective and potent organometallic PIM1 inhibitors. EXPERT OPINION: As PIM1
      possesses oncogenic functions and is overexpressed in various kinds of cancer
      diseases, its inhibition provides a new option in cancer therapy. Based on the
      ability of highly selective organometallic PIM1 inhibitors, promising in vivo
      applicability is expected.

PMID- 22385335
TI  - HLA-DRB1*08:48, a novel allele identified in a Brazilian donor.
AB  - The new allele presents a point mutation at codon 67.1 (ATC->CTC) resulting in a
      conservative change from isoleucine to leucine.

PMID- 22385336
TI  - Stimulus-responsive supramolecular pKa tuning of cucurbit[7]uril encapsulated
      coumarin 6 dye.
AB  - This article reports an efficient host-assisted guest protonation mechanism in
      coumarin 6 (C6) dye, upon its interaction with cucurbit[7]uril (CB7) macrocycle.
      C6 uptakes the CB7 macrocycle both in 1:1 and 2:1 (CB7/C6) stoichiometries, which
      brings out a large upward pK(a) shift (from ~0.8 to 6), and facilitates the
      protonation of C6 at normal pH conditions, having significant photochemical
      implications. Controlled dissociation of the assemblies has been achieved through
      their response to stimuli like temperature change or metal ions. By this
      approach, a specific form of the guest can be activated and could provide a
      simple stimulus for the controlled drug/dye delivery. Furthermore, the host
      assisted guest protonation improves the stability and aqueous solubility of C6
      and is a promising candidate for aqueous-based supramolecular dye laser system.
      Such simple protocol leading to photoswitchable systems having aqueous solubility
      and biocompatibility can in principle be evolved into a general strategy to
      deliver and operate potential functional molecular components under various
      trigger control.

PMID- 22385337
TI  - Ammonia transformations and abundance of ammonia oxidizers in a clay soil
      underlying a manure pond.
AB  - Unlined manure ponds are constructed on clay soil worldwide to manage farm waste.
      Seepage of ammonia-rich liquor into underlying soil layers contributes to
      groundwater contamination by nitrate. To identify the possible processes that
      lead to the production of nitrate from ammonia in this oxygen-limited
      environment, we studied the diversity and abundance of ammonia-transforming
      microorganisms under an unlined manure pond. The numbers of ammonia-oxidizing
      bacteria and anammox bacteria were most abundant in the top of the soil profile
      and decreased significantly with depth (0.5 m), correlating with soil pore-water
      ammonia concentrations and soil ammonia concentrations, respectively. On the
      other hand, the numbers of ammonia-oxidizing archaea were relatively constant
      throughout the soil profile (10(7) amoA copies per g(soil)). Nitrite-oxidizing
      bacteria were detected mainly in the top 0.2 m. The results suggest that nitrate
      accumulation in the vadose zone under the manure pond could be the result of
      complete aerobic nitrification (ammonia oxidation to nitrate) and could exist as
      a byproduct of anammox activity. While the majority of the nitrogen was removed
      within the 0.5-m soil section, possibly by combined anammox and heterotrophic
      denitrification, a fraction of the produced nitrate leached into the groundwater.

PMID- 22385339
TI  - Evaluation of colloid milium by in vivo reflectance confocal microscopy.

PMID- 22385338
TI  - Differences in systemic oxidative stress based on race and the metabolic
      syndrome: the Morehouse and Emory Team up to Eliminate Health Disparities (META
      Health) study.
AB  - BACKGROUND: Classification schema such as metabolic syndrome may underestimate
      cardiovascular disease (CVD) risk in African Americans, despite a higher burden
      of CVD in African Americans. Oxidative stress results from an imbalance of
      prooxidants and antioxidants and leads to endothelial dysfunction that promotes
      vascular inflammation and atherosclerosis. Aminothiol markers of oxidative stress
      are associated with CVD risk factors and metabolic syndrome; however, little is
      known about racial differences in levels of oxidative stress. We sought to
      investigate whether oxidative stress would be higher in African Americans
      compared to whites independently of traditional risk factor burden. METHODS: We
      assessed oxidative stress in a biracial, community-based cohort. In 620 subjects
      (59% female, 52% African American) in the Morehouse and Emory Team up to
      Eliminate Health Disparities (META-Health) study, we measured plasma levels of
      glutathione, an intracellular antioxidant, and its redox potential as a ratio of
      reduced and oxidized glutathione (E(h) glutathione). RESULTS: African Americans
      had lower glutathione levels (P<0.001) compared to whites. There was a trend
      toward more oxidized E(h) glutathione (P = 0.07) in African Americans; however,
      this did not reach statistical significance. After adjustment for demographics
      and CVD risk factors, African-American race remained a significant correlate of
      lower glutathione levels (P<0.001) and a more oxidized E(h) glutathione (P =
      0.04). After further adjustment for high-sensitivity C-reactive protein (hsCRP),
      glutathione remained significantly lower in African Americans (P = 0.001).
      African Americans with or without metabolic syndrome had lower glutathione levels
      compared to whites with or without metabolic syndrome, respectively (both P <=
      0.001), and African Americans without metabolic syndrome had a more oxidized E(h)
      glutathione compared to whites without metabolic syndrome (P = 0.003).
      CONCLUSIONS: African Americans have higher levels of oxidative stress than
      whites, even after adjustment for differences in CVD risk factors and
      inflammation. Racial differences in oxidative stress may play a key role in
      understanding observed racial disparities in CVD.

PMID- 22385340
TI  - Equation of state of a model methane clathrate cage.
AB  - We investigate the behavior of a model methane clathrate cage under high
      hydrostatic pressures. The methane clathrate cage consists of 20 water molecules
      forming 12 pentagonal faces, with a methane molecule positioned at the cage
      center. The clathrate compound is located inside a fullerene-type arrangement of
      180 He atoms to simulate an isotropic pressure. Different pressures are simulated
      by decreasing the radius of the He array. The minimal energy of the total system
      for each configuration is calculated by using density functional theory. The
      variation of the energy with the volume of the imprisoned clathrate cage leads to
      the proposal of a (cold) equation of state in the pressure range [0,60] GPa. The
      elastic parameters of the state equation are found in agreement with equivalent
      quantities measured on clathrates in their sI conformation. Special attention is
      given to the distribution of the confined atoms and the eventual symmetry lost
      from the clathrate cage with the pressure, as the clathrate cage constitutes a
      basic structural unit of the crystal. Finally, the strengths and limitations of
      the model are discussed.

PMID- 22385341
TI  - Mycobacterium tuberculosis Rv0652 stimulates production of tumour necrosis factor
      and monocytes chemoattractant protein-1 in macrophages through the Toll-like
      receptor 4 pathway.
AB  - Mycobacterial proteins interact with host macrophages and modulate their
      functions and cytokine gene expression profile. The protein Rv0652 is abundant in
      culture filtrates of Mycobacterium tuberculosis K-strain, which belongs to the
      Beijing family, compared with levels in the H37Rv and CDC1551 strains. Rv0652
      induces strong antibody responses in patients with active tuberculosis. We
      investigated pro-inflammatory cytokine production induced by Rv0652 in murine
      macrophages and the roles of signalling pathways. In RAW264.7 cells and bone
      marrow-derived macrophages, recombinant Rv0652 induced predominantly tumour
      necrosis factor (TNF) and monocyte chemoattractant protein (MCP)-1 production,
      which was dependent on mitogen-activated protein kinases and nuclear factor
      kappaB. Specific signalling pathway inhibitors revealed that the extracellular
      signal-regulated kinase 1/2 (ERK1/2), p38 and phosphatidylinositol 3-kinase
      (PI3K) pathways were essential for Rv0652-induced TNF production, whereas the
      ERK1/2 and PI3K pathways, but not the p38 pathway, were critical for MCP-1
      production in macrophages. Rv0652-stimulated TNF and MCP-1 secretion by
      macrophages occurred in a Toll-like receptor 4-dependent and MyD88-dependent
      manner. In addition, Rv0652 significantly up-regulated the expression of the
      mannose receptor, CD80, CD86 and MHC class II molecules. These results suggest
      that Rv0652 can induce a protective immunity against M. tuberculosis through the
      macrophage activation.

PMID- 22385343
TI  - Gel formation driven by tunable hydrophobic domain: design of acrylamide
      macromonomer with oligo hydrophobic segment.
AB  - Nowadays, biomaterials with amphiphilic properties are undergoing remarkable
      development. Here, we present one such development, in which we prepared
      amphiphilic graft copolymers, with a main chain composed of hydroxyethyl
      acrylamide (HEAA), to introduce hydrophilicity, and a side chain composed of
      poly(trimethylene carbonate) (PTMC) to introduce tunable hydrophobicity. These
      macromonomers were created with a novel molecular design, which introduced a ring
      opening polymerization by the hydroxyl end group of HEAA in the presence of 1,8
      diazabicyclo[5.4.0]undec-7-ene, and were analyzed by (1)H NMR and gel permeation
      chromatography. The amphiphilic graft copolymers were shown to form a hydrogel,
      the swelling ratio of which was greatly influenced by the number of trimethylene
      carbonate units. These copolymers also exhibited the Tyndall phenomenon in
      aqueous solution; they aggregated spontaneously due to hydrogen bonding and
      hydrophobic interactions, and a sodium 8-anilino-1-naphthalenesulfonate (ANS)
      fluorescence probe was introduced into the hydrophobic domain. The solution
      property of ANS in the polymer solution was analyzed by fluorescence measurement
      and (1)H NMR. The maximum fluorescence wavelength of ANS shifted to shorter
      wavelengths as the degree of polymerization of the hydrophobic PTMC, the
      composition of the macromonomer, and the concentration of the copolymer
      increased. The resulting copolymer formed a polymer micelle structure due to the
      tunable hydrophobic domain formation in selected solvents. Therefore, these
      amphiphilic graft copolymers containing a PTMC segment are excellent candidates
      for use as hydrophobic drug delivery carriers.

PMID- 22385344
TI  - Risk factors of abnormal carbohydrate metabolism after pregnancy complicated by
      gestational diabetes mellitus.
AB  - OBJECTIVE: In gestational diabetes mellitus (GDM) abnormal glucose metabolism
      normalizes soon after delivery. However, the history of GDM predisposes to
      carbohydrate intolerance in the future. The aim of the study was to explore risk
      factors and to evaluate risk of glucose intolerance and diabetes mellitus in
      women with a history of GDM. METHODS: 155 patients entered this case-control
      study. Participants fulfilled the inclusion criteria: a history of GDM, perinatal
      care in the study center. Medical and family history and laboratory findings were
      analyzed. Oral glucose tolerance test (OGTT) was performed. RESULTS: 18.1% of
      patients presented impaired fasting glucose during the study, 20% presented
      impaired glucose tolerance and 23.2% presented diabetes mellitus. Gestational age
      at diagnosis of GDM, the results of OGTT during pregnancy, serum HbA1c
      concentration at 2nd and 3rd trimester, serum fructosamine concentration,
      symptoms of diabetic fetopathy in the neonate, the need for insulin therapy after
      delivery, maternal age at diagnosis of GDM and maternal body mass index before
      pregnancy were the significant risk factors of impaired glucose tolerance or
      diabetes in the future. CONCLUSION: GDM increases the risk of diabetes mellitus.
      Several risk factors of impaired carbohydrate metabolism can be distinguished in
      patients with a history of GDM.

PMID- 22385345
TI  - Comparison of two commercially available ELISA antibody test kits for detection
      of human antibodies against Coxiella burnetii.
AB  - BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii. The disease is
      emerging in many parts of the world, likely in part due to increased awareness
      and the availability of better diagnostic tests. The clinical diagnosis of Q
      fever is difficult, and most confirmed cases rely on serology. METHODS: This
      study compared the sensitivity, specificity, and performance of 2 commercial
      enzyme-linked immunosorbent assay (ELISA) kits, with a commercial
      microimmunofluorescence antibody test (IFA) used as reference. RESULTS: One of
      the ELISA kits showed a higher sensitivity and a lower cross-reactivity than the
      other kit. Likewise, the same kit was superior when comparing the area under the
      receiver operating characteristic curves. CONCLUSIONS: The results support the
      continued use of IFA as a primary serological test for Q fever; for large numbers
      of samples, an ELISA kit can be used as a screening tool, if followed by a
      confirmatory IFA test.

PMID- 22385346
TI  - [4 + 4] photodimerization of azaanthracenes in both solution and solid phase
      controlled by cation-pi interactions.
AB  - Regio- and stereoselective [4 + 4] photodimerization reactions of 1- and 2
      azaanthracenes were performed in both methanol solution and solid phases to give
      anti-HT dimers in high yields. In these reactions, intermolecular cation-pi
      interactions between the pyridinium cation and the benzene ring play a key role
      in preorientation prior to the photodimerization reactions.

PMID- 22385348
TI  - Factor XIII Val34Leu mutation accelerates the development of fibrosis in patients
      with chronic hepatitis B and C.
AB  - AIM:   There is considerable variation in liver fibrosis stage and progression to
      cirrhosis among patients with chronic hepatitis B (CHB) or C (CHC). Coagulation
      pathway activity due to genetic variations could influence the rate of fibrosis.
      We investigated thrombotic risk factors and their association with the extent and
      progression of fibrosis in CHB or CHC patients. METHODS:   In total, 194 patients
      with CHB (n = 88) or CHC (n = 106) were included. Data on demographic and
      laboratory findings were collected. Liver biopsies were evaluated according to
      the Ishak classification system. Fibrosis progression rate (FPR), defined as
      ratio of fibrosis score to duration of infection, was determined for 131
      patients. Prevalence of factor V Leiden, prothrombin G20210A, plasminogen
      activator inhibitor type-1 (PAI-1) 4G/5G and factor XIIIA Val34Leu mutations was
      evaluated. RESULTS:   Heterozygosity for factor V Leiden, prothrombin G20210A,
      PAI-1 4G/5G and factor XIIIA Val34Leu mutations was present in 3.1%, 2.1%, 49%
      and 28% of the patients, respectively. Factor XIII Val34Leu mutation was a risk
      for enhanced FPR (odds ratio 4.7; P = 0.01). In patients with both factor XIII
      Val34Leu and PAI-1 4G/5G mutations the risk of an accelerated FPR was further
      increased (odds ratio 5.0; P = 0.02). Mutations of the other thrombotic genes
      were not significantly associated with fibrosis stage and FPR. CONCLUSION:   Our
      data show that factor XIII Val34Leu mutation alone or in combination with PAI-1
      4G/5G mutation is a risk factor for an increased rate of liver fibrosis
      development in patients with CHB or CHC.

PMID- 22385349
TI  - Premature birth and diseases in premature infants: common genetic background?
AB  - It has been proposed that during human evolution, development of obligate
      bipedalism, narrow birth canal cross-sectional area and the large brain have
      forced an adjustment in duration of pregnancy (scaling of gestational age;
      Plunkett 2011). Children compared to other mammals are born with proportionally
      small brains (compared to adult brains), suggesting shortening of pregnancy
      duration during recent evolution. Prevalence of both obstructed delivery and
      premature birth is still exceptionally high. In near term infants, functional
      maturity and viability is high, and gene variants predisposing to respiratory
      distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment
      practices during the new era of medicine allowed survival of also very preterm
      infants (gestation <32 weeks). Genetic factors may play a major role in
      predisposing these infants to common pulmonary (bronchopulmonary dysplasia [BPD];
      RDS) and intracerebral (intraventricular hemorrhage [IVH], cerebral palsy [CP])
      diseases. Fetal genes also influence the susceptibility to preterm labor and
      premature birth. Specific genes associating with diseases in preterm infants may
      also contribute to the susceptibility to preterm birth. Understanding and
      applying the knowledge of genetic interactions in normal and abnormal perinatal
      neonatal development requires large, well-structured population cohorts, studies
      involving the whole genome and international interdisciplinary collaboration.

PMID- 22385350
TI  - Experience with the Vibrant Soundbridge RW-Coupler for round window Vibroplasty
      with tympanosclerosis.
AB  - Abstract   Usage of the Vibrant Soundbridge (VSB) with round window (RW)-Coupler
      placement at the RW has been shown to successfully treat mixed hearing loss.
      Coupling between the VSB's floating mass transducer (FMT) and the RW membrane is
      difficult in the case of sclerosis in the RW and drilling down the bony lip until
      the RW membrane can be seen completely can possibly induce a perilymphatic
      fistula. A 68-year-old woman who had bilateral mixed hearing loss with sclerosis
      in the RW due to tympanosclerosis underwent a RW-Vibroplasty with a RW-Coupler.
      Speech discrimination scores in quiet and noise and functional gain with the VSB
      with RW-Coupler were better than those using a conventional hearing aid. The
      results of the present case have shown the feasibility of implanting a VSB with
      RW-Coupler in patients with mixed hearing loss due to tympanosclerosis.

PMID- 22385353
TI  - Purification and characterization of alpha-galactosidase from white chickpea
      (Cicer arietinum).
AB  - Glycosylated alpha-galactosidase (melibiase) has been purified from white
      chickpea ( Cicer arietinum ) to 340-fold with a specific activity of 61 units/mg.
      Cicer alpha-galactosidase showed a M(r) of 45 kDa on SDS-PAGE and by MALDI-TOF.
      The optimum pH and temperature with pNPGal were 4.5 and 50  degrees C,
      respectively. The K(m) for hydrolysis of pNPGal was 0.70 mM. Besides hydrolyzing
      the pNPGal, Cicer alpha-galactosidase also hydrolyzed natural substrates such as
      melibiose, raffinose, and stachyose very effectively; hence, it can be exploited
      commercially for improving the nutritional value of soy milk. Galactose was found
      to be a competitive inhibitor. The property of this enzyme to cleave the terminal
      galactose residues can be utilized for converting the group B erythrocytes to
      group O erythrocytes.

PMID- 22385354
TI  - Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal
      carcinoma.
AB  - AIMS: To investigate the aberrant expression of N-cadherin in nasopharyngeal
      carcinoma (NPC) and its prognostic significance. METHODS AND RESULTS:
      Immunohistochemical staining for N-cadherin protein was performed on tissue
      microarray (TMA) from 122 NPC patients. Cytoplasmic N-cadherin was observed in
      42.6% and nuclear N-cadherin in 45.1% of NPC tissues. High expression of
      cytoplasmic and nuclear N-cadherin was associated with a majority of the
      clinicopathological variables, including lymph node metastasis, distant
      metastasis and clinical stage. Cytoplasmic N-cadherin was associated positively
      with nuclear N-cadherin expression (P = 0.000). In univariate analysis,
      cytoplasmic N-cadherin showed no significant impact on patient prognosis. In
      contrast, the overall survival was significantly shorter in patients with high
      nuclear N-cadherin than those with low levels of staining (P = 0.002). A high
      expression of nuclear N-cadherin predicted poorer survival in patients with late
      stage disease (P = 0.033), but not those with early tumour stage. In addition,
      multivariate analysis showed nuclear N-cadherin to bean independent prognostic
      marker for NPC patients (P = 0.024). CONCLUSIONS: Nuclear N-cadherin expression
      may represent a valuable prognostic marker in NPC patients, especially those with
      late stage disease.

PMID- 22385355
TI  - Formation of unimer nanoparticles by controlling the self-association of
      hydrophobically modified poly(amino acid)s.
AB  - Amphiphilic block or graft copolymers have been demonstrated to form a variety of
      self-assembled nano/microstructures in selective solvents. In this study, the
      self-association behavior of biodegradable graft copolymers composed of
      poly(gamma-glutamic acid) (gamma-PGA) as the hydrophilic segment and L
      phenylalanine (Phe) as the hydrophobic segment in aqueous solution was
      investigated. The association behavior and unimer nanoparticle formation of these
      gamma-PGA-graft-Phe (gamma-PGA-Phe) copolymers in aqueous solution were
      characterized with a focus on the effect of the Phe grafting degree on the intra-
      and interpolymer association of gamma-PGA-Phe. The particle size and number of
      polymer aggregates (N(agg)) in one particle of the gamma-PGA-Phe depended on the
      Phe grafting degree. The size of gamma-PGA-Phe with 12, 27, 35, or 42% Phe
      grafting (gamma-PGA-Phe-12, -27, -35, or -42) was about 8-14 nm and the N(agg)
      was about 1, supporting the presence of a unimolecular graft copolymer in PBS.
      The pyrene fluorescence data indicated that gamma-PGA-Phe-35 and -42 have
      hydrophobic domains formed by the intrapolymer association of Phe attached to
      gamma-PGA. These results suggest that the Phe grafting degree is critical to the
      association behavior of gamma-PGA-Phe and that gamma-PGA-Phe-35 and -42 could
      form unimer nanoparticles. Moreover, when gamma-PGA-Phe-42 dissolved in DMSO was
      added to various concentrations of NaCl solution, the particle size and N(agg)
      could be easily controlled by changing the NaCl concentration during the
      formation of the particles. These results suggest that biodegradable gamma-PGA
      Phe is useful for the fabrication of very small nanoparticles. It is expected
      that gamma-PGA-Phe nanoparticles, including unimer particles, will have great
      potential as multifunctional carriers for pharmaceutical and biomedical
      applications, such as drug and vaccine delivery systems.

PMID- 22385356
TI  - Desflurane-induced and ischaemic postconditioning against myocardial infarction
      are mediated by Pim-1 kinase.
AB  - BACKGROUND: Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST)
      against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt.
      Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to
      enhance cardiomyocyte survival. We tested the hypothesis that both APOST and
      IPOST are mediated by Pim-1 kinase. METHODS: Pentobarbital-anaesthetized male
      C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h
      reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor
      II (10 MUg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 MUl/g
      intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar
      concentration desflurane was administered for 18 min alone or in combination with
      Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s
      ischaemia/reperfusion, and animals received either IPOST alone or in combination
      with Pim-1 kinase inhibitor II. Infarct size was determined with
      triphenyltetrazolium chloride and area at risk with Evans blue. Protein
      expression of Pim-1 kinase, Bad, phospho-Bad(Ser112)  and B-cell lymphoma 2 was
      determined using Western immunoblotting analysis. RESULTS: Infarct size in
      control animals (CON) was 46 +/- 3%. Dimethylsulfoxide (47 +/- 3%) and Pim-1
      kinase inhibitor II (44 +/- 5%) did not significantly reduce infarct size.
      Desflurane (16 +/- 2%*; *P < 0.05 vs. CON) and IPOST (21 +/- 2%*) significantly
      reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished
      desflurane-induced postconditioning (46 +/- 4%) and IPOST (44 +/- 5%). Western
      blot analysis revealed that only desflurane enhances phosphorylation of Bad at
      serine 112 that was abrogated by Pim-1 kinase inhibitor II. CONCLUSION: These
      data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning
      and IPOST in mice.

PMID- 22385357
TI  - Structural diversity in coordination self-assembled networks of a multimodal
      ligand azacalix[4]pyrazine.
AB  - We report herein the synthesis of a new heteracalixaromatic compound,
      tetramethylazacalix[4]pyrazine (TAPz), and its coordination self-assemblies with
      metal and metal cluster centers. Structural characterization of TAPz has shown
      that its conformation is fluxional in solution but exhibits a dominant 1,3
      alternate configuration in the crystalline solid state, wherein its convergent
      chelating coordination sites are orthogonal to the 120 degrees -angled bridging
      sites, thus forming a unique multimodal ligand. Compound TAPz reacting with
      silver, zinc metal centers, and Cu(x)I(x) cluster centers leads to the
      construction of diverse coordination network structures in 1-5 including
      honeycomb, Kagome, alpha-quartz, and cavity-involved two-dimensional layers. The
      structural diversity of these network structures is conducted by different
      combination modes between the chelation bonding sites of TAPz and metal or metal
      cluster centers. This system may afford deeper insight on the fantastic use of
      macrocyclic compounds on the designed synthesis of coordination network
      structures through the proper arrangement of their coordination sites.

PMID- 22385359
TI  - Silicon nanopillars for field-enhanced surface spectroscopy.
AB  - Silicon nanowire and nanopillar structures have drawn increased attention in
      recent years due in part to their unique optical properties. Herein, electron
      beam lithography combined with reactive-ion etching is used to reproducibly
      create individual silicon nanopillars of various sizes, shapes, and heights.
      Finite difference time domain analysis predicts local field intensity
      enhancements in the vicinity of appropriately sized and coaxially illuminated
      silicon nanopillars of approximately 2 orders of magnitude. While this level of
      enhancement is modest when compared to plasmonic systems, the unique advantage of
      the silicon nanopillar resonators is that they enhance optical fields in
      substantially larger volumes. By analyzing experimentally measured strength of
      the silicon Raman phonon line (500 cm(-1)), it was determined that nanopillars
      produced local field enhancements that are consistent with these predictions.
      Additionally, we demonstrate that a thin layer of Zn phthalocyanine on the
      nanopillar surface with a total amount of <30 attomoles produced prominent Raman
      spectra, yielding enhancement factors (EFs) better than 2 orders of magnitude.
      Finally, silicon nanopillars of cylindrical and elliptical shapes were labeled
      with different fluorophors and evaluated for their surface-enhanced fluorescence
      (SEF) capability. The EFs derived from analysis of the acquired fluorescence
      microscopy images indicate that silicon nanopillar structures can provide
      enhancements comparable or even stronger than those typically achieved using
      plasmonic SEF structures without the limitations of the metal-based substrates,
      such as fluorescence quenching and an insufficiently large probe volume. It is
      anticipated that dense arrays of silicon nanopillars will enable SEF assays with
      extremely high sensitivity, while a broader impact of the reported phenomena is
      anticipated in photovoltaics, subwavelength light focusing, and fundamental
      nanophotonics.

PMID- 22385361
TI  - Psychrophilic yeasts from worldwide glacial habitats: diversity, adaptation
      strategies and biotechnological potential.
AB  - Glacial habitats (cryosphere) include some of the largest unexplored and extreme
      biospheres on Earth. These habitats harbor a wide diversity of psychrophilic
      prokaryotic and eukaryotic microorganisms. These highly specialized
      microorganisms have developed adaptation strategies to overcome the direct and
      indirect life-endangering influence of low temperatures. For many years
      Antarctica has been the geographic area preferred by microbiologists for studying
      the diversity of psychrophilic microorganisms (including yeasts). However, there
      have been an increasing number of studies on psychrophilic yeasts sharing the non
      Antarctic cryosphere. The present paper provides an overview of the distribution
      and adaptation strategies of psychrophilic yeasts worldwide. Attention is also
      focused on their biotechnological potential, especially on their exploitation as
      a source of cold-active enzymes and for bioremediation purposes.

PMID- 22385362
TI  - Cavity closure dynamics of peracetylated beta-cyclodextrins in supercritical
      carbon dioxide.
AB  - Structural properties of peracetylated beta-cyclodextrin in supercritical carbon
      dioxide were investigated by means of molecular dynamics simulations. The study
      indicated a strong reduction of the cavity accessibility to guest molecules,
      compared to native beta-cyclodextrin in water. Indeed, the cavity is self-closed
      during the largest part of the simulation, which agrees well with suggestions
      made on the basis on high-pressure NMR experiments. Self-closure happens because
      one glucose unit undergoes a main conformational change (from chair to skew) that
      brings one of the acetyl groups in the wide rim of the cyclodextrin to the cavity
      interior. This arrangement turns out to be quite favorable, persisting for
      several nanoseconds. In addition to the wide rim self-closure, a narrow rim self
      closure may also occur, though it is less likely and exhibits short duration (<1
      ns). Therefore, the number of solvent molecules reaching the cavity interior is
      much smaller than that found in the case of native beta-cyclodextrin in water
      after correction to account for different molar densities. These findings support
      the weak tendency of the macromolecule to form host-guest complexes in this
      nonconventional medium, as reported by some experiments. Finally, Lewis acid/base
      interactions between the acetyl carbonyl groups and the solvent CO(2) molecules
      were analyzed through ab initio calculations that revealed the existence of a
      quite favorable four-member ring structure not yet reported. The ensemble of
      these results can contribute to establish general thermodynamic principles
      controlling the formation of inclusion complexes in supercritical CO(2), where
      the hydrophilicity/hydrophobicity balance is not applicable.

PMID- 22385360
TI  - Mutations in LPAR6/P2RY5 and LIPH are associated with woolly hair and/or
      hypotrichosis.
AB  - BACKGROUND: Woolly hair (WH) belongs to a family of disorders characterized by
      hair shaft anomalies that clinically presents with tightly curled hair, which can
      be divided into syndromic and non-syndromic forms of WH. We have recently
      identified mutations in both LPAR6/P2RY5 and LIPH that are associated with
      autosomal recessive woolly hair (ARWH). OBJECTIVE: To study the underlying
      genetic causes of autosomal woolly hair in Pakistani population. METHODS: We
      studied 10 Pakistani families with ARWH for mutations in LPAR6/P2RY5 and LIPH and
      then performed haplotype analysis to confirm their segregation in the families.
      RESULTS: We identified five mutations in LPAR6/P2RY5, among which three were
      recurrent and two were novel in eight Pakistani families. We then showed that two
      of the mutations in LPAR6/P2RY5 are founder mutations in Pakistani families.
      Moreover, we identified two recurrent mutations in the LIPH gene in two Pakistani
      families. CONCLUSION: Our study extends the spectrum of mutations in LPAR6/P2RY5
      gene and underscores those mutations in LPAR6/P2RY5 and LIPH result in similar
      phenotypes.

PMID- 22385363
TI  - A survey of opinions on emergency contraception in young women in Southern Italy.
AB  - OBJECTIVE: To assess opinions and attitudes towards the use of hormonal emergency
      contraception (HEC) in a sample of young women in Puglia, Italy. METHODS: A self
      administered standardised anonymous questionnaire was administered to female
      school-leavers who were attending a preparatory course at the University of Bari.
      RESULTS: Seven hundred and fifty-four women, with an average age of 19.5 years,
      completed the questionnaire. Sixteen percent of respondents had used HEC and 3%
      had used it more than once. The reasons given for resorting to HEC were: rupture
      of the condom (57%), the lack of thought about the risk of an undesired pregnancy
      (25%), and the unavailability of contraceptives at the time of coitus (18%).
      CONCLUSIONS: The opinions expressed by the interviewees in our survey do not
      suggest that the use of HEC would increase the risks linked to sexual behaviour.
      In Italy, over-the-counter availability of HEC should be implemented in parallel
      with the improvement of sex education programmes aimed at the young.

PMID- 22385364
TI  - Neurocognitive performance in drug-dependent males and females with posttraumatic
      stress disorder symptoms.
AB  - Sex differences in neurobiological mechanisms of substance dependence are well
      documented but studies of sex differences in associated neurocognitive deficits
      have produced inconsistent results. Posttraumatic stress disorder (PTSD) is
      comorbid with substance dependence and frequently affects neurocognition. Thus,
      we investigated the effects of sex and PTSD symptoms on sustained attention and
      inhibition abilities among 126 female and 297 male substance-dependent
      individuals (SDIs) using the Immediate Memory Test (IMT). Females with
      significant PTSD (PTSD+) symptoms demonstrated significantly impaired IMT
      performance relative to other participants. These results represent progress in
      efforts to delineate sex-specific risk factors for neurocognitive deficits among
      SDIs.

PMID- 22385365
TI  - Restricted photochemistry in the molecular solid state: structural changes on
      photoexcitation of Cu(I) phenanthroline metal-to-ligand charge transfer (MLCT)
      complexes by time-resolved diffraction.
AB  - The excited-state structure of [Cu(I)[(1,10-phenanthroline-N,N')
      bis(triphenylphosphine)] cations in their crystalline [BF(4)] salt has been
      determined at both 180 and 90 K by single-pulse time-resolved synchrotron
      experiments with the modified polychromatic Laue method. The two independent
      molecules in the crystal show distortions on MLCT excitation that differ in
      magnitude and direction, a difference attributed to a pronounced difference in
      the molecular environment of the two complexes. As the excited states differ, the
      decay of the emission is biexponential with two strongly different lifetimes, the
      longer lifetime, assigned to the more restricted molecule, becoming more
      prevalent as the temperature increases. Standard deviations in the current Laue
      study are very much lower than those achieved in a previous monochromatic study
      of a Cu(I) 2,9-dimethylphenanthroline substituted complex (  J. Am. Chem. Soc.   
      2009  ,   131  ,   6566  ), but the magnitudes of the shifts on excitation are
      similar, indicating that lattice restrictions dominate over the steric effect of
      the methyl substitution. Above all, the study illustrates emphatically that
      molecules in solids have physical properties different from those of isolated
      molecules and that their properties depend on the specific molecular environment.
      This conclusion is relevant for the understanding of the properties of molecular
      solid-state devices, which are increasingly used in current technology.

PMID- 22385369
TI  - Editors' comments.

PMID- 22385366
TI  - Immunological effects and tolerability of a new fast updosed immunologically
      enhanced subcutaneous immunotherapy formulation with optimized allergen/adjuvant
      ratio.
AB  - BACKGROUND: Subcutaneous immunotherapy (SCIT) traditionally includes an updosing
      phase injecting increasing doses of allergen over a period of several weeks,
      followed by a maintenance phase. To establish shorter and more convenient
      updosing schedules, a fast updosed immunologically enhanced SCIT formulation has
      been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio.
      METHODS: In a randomized, controlled, parallel-group trial, patients with grass
      pollen induced rhinoconjunctivitis with/without asthma were treated with an
      immunologically enhanced SCIT formulation (AVANZ, ALK, Denmark). The trial
      included updosing with five injections (300, 600, 3000, 6000 and 15,000 SQ+)
      injected either in weekly interval (Group 1) or in 3-4 days interval (Group 2)
      followed by two maintenance injections (15,000 SQ+), approximately 10 weeks
      treatment. The immunological effects (primary endpoint) and tolerability
      (secondary endpoint) of the updosing schedules were evaluated. RESULTS: Four
      hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an
      immunological response with statistically significant increases in levels of IgE
      blocking factor, IgG(4) and IgE (P < 0.001), was induced from baseline to end of
      trial. Most frequently reported adverse events were local injection site
      reactions such as injection site swellings (Group 1: 30% of patients, Group 2:
      41% of patients). Other frequently reported adverse events included systemic
      reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to
      moderate allergic rhinitis and urticaria. CONCLUSIONS: Fast updosed
      immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced
      significant immunological effects and had an acceptable safety profile. Clinical
      efficacy will be investigated in future clinical trials.

PMID- 22385370
TI  - Genotypic and phenotypic characterization of Staphylococcus epidermidis causing
      chronic relapsing prosthetic joint infections.
AB  - Twenty-one isolates of Staphylococcus epidermidis from 9 patients with persistent
      prosthetic joint infections were analysed by pulsed-field gel electrophoresis and
      antibiotic susceptibility assays. In 7 of these cases, the S. epidermidis isolate
      was different from that of the initial episode. In 1 further case, the
      superinfection was polyclonal. Recurrence, i.e., renewed isolation of a clone
      identical to that of an initial episode, occurred in 3 cases, 1 of which was in
      the absence of superinfection. A high degree of antibiotic resistance was
      demonstrated, including methicillin in 17 of 21 strains. In conclusion, a
      frequent occurrence of superinfection and a high degree of resistance make
      management of these infections complex.

PMID- 22385371
TI  - Ultralow fouling polyacrylamide on gold surfaces via surface-initiated atom
      transfer radical polymerization.
AB  - In this work, polyacrylamide is investigated as an ultralow fouling surface
      coating to highly resist protein adsorption, cell adhesion, and bacterial
      attachment. Polyacrylamide was grafted on gold surfaces via surface-initiated
      atom transfer radical polymerization (ATRP). Protein adsorption from a wide range
      of biological media, including single protein solutions of fibrinogen, bovine
      serum albumin, and lysozyme, dilute and undiluted human blood serum, and dilute
      and undiluted human blood plasma, was studied by surface plasmon resonance (SPR).
      Dependence of the protein resistance on polyacrylamide film thickness was
      examined. With the optimal film thickness, the adsorption amount of all three
      single proteins on polyacrylamide-grafted surfaces was <3 pg/mm(2), close to the
      detection limit of SPR. The average nonspecific adsorptions from 10% plasma, 10%
      serum, 100% plasma, and 100% serum onto the polyacrylamide-grafted surfaces were
      5, 6.5, 17, and 28 pg/mm(2), respectively, comparable (if not better) than the
      adsorption levels on poly(ethylene glycol) (PEG) and zwitterionic
      poly(sulfobetaine methacrylate) surfaces, the best antifouling materials known to
      date. The polyacrylamide-grafted surfaces were also shown strongly resistant to
      adhesion from bovine aortic endothelial cells and two bacterial species, Gram
      positive  Staphylococcus epidermidis  ( S. epidermidis ) and Gram-negative 
      Pseudomonas aeruginosa  ( P. aeruginosa ). Strong hydrogen bond with water is
      considered the key attribute for the ultralow fouling properties of
      polyacrylamide. This is the first work to graft gold surfaces with polyacrylamide
      brushes via ATRP to achieve ultralow fouling surfaces, demonstrating that
      polyacrylamide is a promising alternative to traditional PEG-based antifouling
      materials.

PMID- 22385373
TI  - Cognitive reserve, age, and their relation to attentional and executive
      functions.
AB  - The main objective of this research was to establish the relation between age,
      cognitive reserve (CR), and attentional and executive functions. One hundred and
      sixty healthy participants aged 20 to 65 years old completed a wide battery of
      frontal-lobe tasks using classical tests that assess planning and control of
      movement, problem solving, and inhibition of automatic response, visuomotor
      tracking, focused and sustained attention, shifting, spontaneity and reasoning.
      The total sum of the score in premorbid IQ (by means of the Weschsler Adult
      Intelligence Scale Vocabulary subtest), educational level, and type of profession
      was used as a proxy of CR. Subjects were divided into groups of low or high CR.
      Multiple linear and logistic analyses revealed that age is a predictor of the 20Q
      Test, Terman Merril's Picture task, Similarities, Digit Span (backward), Trail
      Making Tests, Porteus Maze Trace, the "A" Letter Cancellation Test, and
      reciprocal inhibition. CR is a predictor of the Controlled Oral Word Association
      Test, Trail-Making Tests A and B, Digit Span (forward), and Similarities. In
      conclusion, a higher CR score is associated with better performance in almost all
      tests employed. But it has a significant contribution to performance on verbal
      fluency, behavioral spontaneity, reasoning, divided and complex attention, and
      working memory functions, which are mainly related to the dorsolateral prefrontal
      area.

PMID- 22385374
TI  - Assessing cognition in schizophrenia: a comparison of clinician and computerized
      test administration.
AB  - Cognitive impairment is recognized as an important determinant of outcome in
      schizophrenia, but mental health services generally have little capacity to
      provide detailed neuropsychological assessments. Computerized testing would
      overcome this difficulty, provided that such testing was equivalent to testing by
      a clinician. Given that negative symptoms can include impaired motivation and
      attention, it is also important to know whether computerized testing is valid in
      people with more severe negative symptoms. Our study was designed to compare
      clinician-administered and computerized testing of two domains commonly impaired
      in schizophrenia, verbal memory and verbal fluency. We also evaluated the effect
      of negative symptoms on performance on computerized cognitive tests.   Sixty-two
      participants with schizophrenia completed clinician-administered and computerized
      verbal memory and verbal fluency tasks. The Positive and Negative Syndrome Scale
      assessed negative symptom severity. The study found no difference in cognitive
      performance associated with the method of test administration. This finding held
      regardless of the severity of negative symptoms. We found that computerized
      cognitive testing was equivalent to clinician-delivered testing in assessing
      verbal memory and verbal fluency. This finding was not affected by the presence
      of negative symptoms. Our results support the use of computerized cognitive
      testing for people with schizophrenia.

PMID- 22385375
TI  - Cognitive reserve as a protective factor in older HIV-positive patients at risk
      for cognitive decline.
AB  - The present study examined the impact of cognitive reserve in maintaining intact
      neuropsychological (NP) function among older HIV-positive individuals, a uniquely
      at-risk subgroup. Participants included 129 individuals classified by HIV
      serostatus, age group, and NP impairment. A three-way analysis of variance
      (ANOVA) followed by a series of within-group ANOVA and multiple regression
      analyses were conducted to investigate the pattern of cognitive reserve (vs.
      other protective) influence among groups with varying risks of NP impairment.
      Results indicated a significant age * HIV status interaction, with older HIV
      positive individuals demonstrating higher cognitive reserve than subgroups with
      less risk for NP compromise (younger age and/or HIV-negative). Results
      demonstrated higher cognitive reserve specific to NP-intact older HIV-positive
      individuals. Within this group, the interaction of younger age and higher
      cognitive reserve independently contributed to cognitive status when controlling
      for psychiatric, immunological, and psychosocial protective mechanisms,
      suggesting the importance of cognitive reserve beyond other protective mechanisms
      in maintaining optimal NP functioning in those individuals most at risk.
      Alongside younger age, factors contributing to cognitive reserve (i.e., education
      and estimated premorbid intelligence) may provide substantial benefit for older
      HIV-positive adults who are at high risk for NP compromise.

PMID- 22385376
TI  - The use of psychometrists in clinical neuropsychology: history, current status,
      and future directions.
AB  - In recent years, the National Academy of Neuropsychology and other professional
      neuropsychological organizations have published a number of articles and position
      papers regarding the use, education, and training of psychometrists
      ("technicians"). Although these documents provide guidelines for the suggested
      qualifications and training procedures of psychometrists, none make any mention
      of the need for a standardized credentialing process, which is commonly required
      of technicians in similar fields, especially in medical settings. Given the
      recent changes in current procedural Terminology codes used to bill for
      neuropsychological services and the interpretation of legislation disallowing the
      use of psychometrists in New York, the need for a standard credential for
      psychometrists is apparent. This article will review the history and current use
      of psychometrists in clinical neuropsychology and highlight the need and
      rationale for the credentialing of psychometrists.

PMID- 22385377
TI  - The assessment of premorbid intellectual ability following right-hemisphere
      stroke: reliability of a lexical decision task.
AB  - Comparing current with estimated premorbid performance helps identify acquired
      cognitive deficits after brain injury. Tests of reading pronunciation, often used
      to measure premorbid ability, are inappropriate for stroke patients with motor
      speech problems. The Spot-the-Word Test (STWT), a measure of lexical decision,
      offers an alternative approach for estimating premorbid capacity in those with
      speech problems. However, little is known about the STWT's reliability. In the
      present study, a consecutive sample of right-hemisphere stroke (RHS) patients (n
      = 56) completed the STWT at 4 and 16 weeks poststroke. A control group,
      individually matched to the patients for age and initial STWT score, also
      completed the STWT on two occasions. More than 80% of patients had STWT scores at
      retest within 2 scaled score points of their initial score, suggesting that the
      STWT is a reliable measure for most individuals with RHS. However, RHS patients
      had significantly greater score change than controls. Limits of agreement
      analysis revealed that approximately 1 in 7 patients obtained abnormally large
      STWT score improvements at retest. It is concluded that although the STWT is a
      useful assessment tool for stroke clinicians, this instrument may significantly
      underestimate premorbid level of ability in approximately 14% of stroke patients.

PMID- 22385378
TI  - Evidence of carry-over in memory test batteries using RBANS and screening
      measures.
AB  - When testing memory and cognitive abilities, clinicians often administer
      batteries including multiple tests with similar content. Care must be taken so
      that such similarities do not unduly impact test performance. This brief report
      reviews findings from our own clinic, where administration of the Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS) in tandem with
      other screening instruments has led to apparent carry-over at an overall rate of
      more than one third of cases. Specific combinations of RBANS plus three other
      instruments are reported, along with cautions and caveats for appropriate
      interpretation.

PMID- 22385379
TI  - Attention, motivation, and reading coherence failure: a neuropsychological
      perspective.
AB  - Reading coherence, defined as the ability to create appropriate, meaningful
      connections between the elements within a specific text itself and between
      elements within a text and the reader's prior knowledge, is one of the key
      processes involved in reading comprehension. This article describes reading
      coherence within the context of a neuropsychological model combining recent
      research in motivation, attention, and working memory. Specifically, a unique
      neuropsychologically identifiable form of reading coherence failure arising from
      the attentional and motivational deficiencies, based in altered frontoventral
      striatal reward circuits associated with noradrenaline (NA) circuitry, consistent
      with the delay-aversion model (dual-pathway model) of Sonuga-Barke ( 2003 ) is
      postulated. This article provides a model for this subset of reading disorders of
      which etiology is based on the executive support processes for reading and not in
      the mechanics of actual reading such as decoding and phonetics.

PMID- 22385380
TI  - A pilot study of the sensitivity and specificity analysis of the standard-Spanish
      version of the Culture-Fair Assessment of Neurocognitive Abilities and the Examen
      Cognoscitivo Mini-Mental in the Dominican Republic.
AB  - This pilot study purports to address the need for culturally validated, evidence
      based assessments and to serve as a springboard for future culturally sensitive
      research. This study was conducted in the Dominican Republic. It entailed
      counterbalanced administration of a standard Spanish translation of the Culture
      Fair Assessment of Neurocognitive Abilities (S-S CANA) and the standard Spanish
      translation of the Mini-Mental State Examination (Examen Cognoscitivo Mini
      Mental; ECM-M). The sample was composed of 30 Spanish-speaking Dominican adults
      who met the inclusion criteria for the normative and clinical groups. In an
      effort to initiate the validation process for the S-S CANA, as well as norm it to
      the given population, the efficacy of the S-S CANA in determining neuropathology
      was then compared to that of the ECM-M. Analyses of variance and covariance and t
      tests were conducted, and a receiver-operating characteristic curve was computed.
      Results indicated significantly greater sensitivity and specificity of the S-S
      CANA relative to the ECM-M.

PMID- 22385381
TI  - Improving test interpretation for detecting executive dysfunction in adults and
      older adults: prevalence of low scores on the test of verbal conceptualization
      and fluency.
AB  - Knowing the prevalence of low scores on a battery of executive-functioning tests
      supplements clinical interpretation and can reduce the likelihood of
      misdiagnosing deficits in executive functioning. The purpose of this study is to
      examine the base rates of low scores on the Test of Verbal Conceptualization and
      Fluency (TVCF; Reynolds & Horton, 2006 ) in healthy adults (n = 332; M (age) =
      33.0 years, SD = 10.5, range = 20-59) and older adults (n = 138; M (age) = 74.9
      years, SD = 7.8, range = 60-89) from the TVCF standardization sample. The TVCF
      consists of four tests of executive functioning (i.e., Category Fluency, Letter
      Naming, Classification, and Trails C) that provide five age-adjusted T-scores.
      The prevalence of low scores was examined in the total sample and was stratified
      by educational level. When the five T-scores were considered simultaneously,
      having one or more scores that were 1 standard deviation (SD) below the mean was
      found in 28% of healthy adults and 38% of older adults. Education-based
      differences were also present with more lenient cutoff scores (e.g., 1 SD) but
      not with more conservative cutoffs. Consistent with the existing literature on
      other test batteries, at least one low subtest score on the TVCF is common in
      healthy adults and older adults.

PMID- 22385382
TI  - Atypical sensory alien hand syndrome: a case study.
AB  - Alien hand syndrome is a term used to describe a variety of rare conditions in
      which uncontrolled behavior or feelings of strangeness are felt in one extremity,
      most commonly the left hand. Etiology usually involves infarct of the right
      anterior or posterior cerebral arteries or cortical-basal degeneration. The
      medical and neuropsychological data of an elderly female who suffered a left
      middle cerebral artery stroke with resulting right-sided alien hand sign is
      presented. Neuropsychological assessment revealed declines in visual- and
      perceptual-based abilities and right-sided motor and sensory abilities consistent
      with the affected areas indicated on neuroimaging. This case demonstrates the
      utility of neuropsychological assessment in patients with unusual sensory/motor
      presentations.

PMID- 22385384
TI  - Differential intestinal M-cell gene expression response to gut commensals.
AB  - Different rates of bacterial translocation across the gut mucosa have been
      reported but few studies have examined translocation of commensals at the level
      of the gut epithelial microfold (M) cell. We used an in vitro M-cell model to
      quantify translocation and determine the transcriptional response of M cells to
      various commensal bacteria. The transport kinetics and gene expression profile of
      M cells in response to different bacterial strains, namely Lactobacillus
      salivarius, Escherichia coli and Bacteroides fragilis, was assessed. Bacterial
      strains translocated across M cells with different efficiencies; E. coli and B.
      fragilis translocated with equal efficiency whereas L. salivarius translocated
      with less efficiency. Microarray analysis of the M cell response showed both
      common and differential gene expression changes between the bacterial strains. In
      the presence of bacteria, but not control beads, up-regulated genes were mainly
      involved in transcription regulation whereas pro-inflammatory and stress response
      genes were primarily up-regulated by E. coli and B. fragilis, but not L.
      salivarius nor beads. Translocation of bacteria and M-cell gene expression
      responses were confirmed in murine M cells following bacterial challenge in vivo.
      These results demonstrate that M cells have the ability to discriminate between
      different commensal bacteria and modify subsequent immune responses.

PMID- 22385385
TI  - Nickel-catalyzed cross-coupling of chromene acetals and boronic acids.
AB  - A modular and highly efficient protocol for the synthesis of 2-aryl- and
      heteroaryl-2H-chromenes is described. Under base-free conditions, readily
      accessible 2-ethoxy-2H-chromenes undergo C(sp(3))-O activation and C(sp(3))-C
      bond formation in the presence of an inexpensive nickel catalyst and boronic
      acids. This new strategy enables broad access to 2-substituted-2H-chromenes and
      has been applied to the late-stage incorporation of complex molecules, including
      the pharmaceuticals loratidine and indomethacin methyl ester.

PMID- 22385386
TI  - Airflow and temperature distribution inside the maxillary sinus: a computational
      fluid dynamics simulation.
AB  - CONCLUSION: The airflow velocity and flux in maxillary sinuses were much lower
      than those in the nasal cavity, and the temperature in maxillary sinuses was much
      higher than the temperature in the middle meatus. With the increase of maximum
      diameter of the ostium, the above indices changed little. OBJECTIVES: The purpose
      of the paper was to investigate, first, the flow and temperature distribution
      inside normal maxillary sinus in inspiration, and second, flow and temperature
      alteration with the increase of maximum ostium diameter. METHODS: Three
      dimensional models with nasal cavities and bilateral maxillary sinuses were
      constructed for computational fluid dynamics analysis. Virtual surgeries were
      implemented for the maxillary ostium, the maximum diameters of which were 8, 10,
      12, and 15 mm, respectively. The finite volume method was used for numerical
      simulation. The indices of velocity, pressure, vector, and temperature were
      processed and compared between models. RESULTS: The airflow velocity in maxillary
      sinuses (average velocity 0.062 m/s) was much lower than that in the middle
      meatus (average velocity 3.26 m/s). With the increase of ostium diameter, airflow
      characteristics distributed in the maxillary sinuses changed little. The normal
      temperature in the maxillary sinus remained almost constant at 34 degrees C and
      changed little with the increase of ostium diameter.

PMID- 22385387
TI  - Formation of coffee stains on porous surfaces.
AB  - During the drying of drops of nanoparticle suspensions, segregation can occur by
      internal fluid flows toward the contact line, if the contact line is pinned. This
      leads to a characteristic ring deposit or coffee stain. On solid substrates
      coffee staining can be eliminated through the use of solvent mixtures that
      promote Marangoni flows to oppose these drying-induced flows. Here it is shown
      that a suspension, optimized to eliminate the formation of coffee stains on a
      range of solid surfaces, shows coffee staining on a number of porous surfaces.
      This behavior is shown to be consistent with a mechanism of fluid removal through
      capillary flow (draining) of the solvent into the porous substrate, combined with
      filtration of the particles by the small pore size, in addition to the flow from
      solvent evaporation. The extent of capillary driven coffee staining is a function
      of substrate pore size: if the pore size is small, capillary flow is slow,
      reducing the observed coffee staining. However, if the pore size is too large,
      the nanoparticles are absorbed into the material along with the draining solute
      and no deposition of particles is observed.

PMID- 22385388
TI  - Re-audit of revised method for assessing the mitotic component of histological
      grade in needle core biopsies of invasive carcinoma of the breast.

PMID- 22385389
TI  - Three useful dimensions for domain applicability in QSAR models using random
      forest.
AB  - One popular metric for estimating the accuracy of prospective quantitative
      structure-activity relationship (QSAR) predictions is based on the similarity of
      the compound being predicted to compounds in the training set from which the QSAR
      model was built. More recent work in the field has indicated that other
      parameters might be equally or more important than similarity. Here we make use
      of two additional parameters: the variation of prediction among random forest
      trees (less variation among trees indicates more accurate prediction) and the
      prediction itself (certain ranges of activity are intrinsically easier to predict
      than others). The accuracy of prediction for a QSAR model, as measured by the
      root-mean-square error, can be estimated by cross-validation on the training set
      at the time of model-building and stored as a three-dimensional array of bins.
      This is an obvious extension of the one-dimensional array of bins we previously
      proposed for similarity to the training set [Sheridan et al. J. Chem. Inf.
      Comput. Sci.2004, 44, 1912-1928]. We show that using these three parameters
      simultaneously adds much more discrimination in prediction accuracy than any
      single parameter. This approach can be applied to any QSAR method that produces
      an ensemble of models. We also show that the root-mean-square errors produced by
      cross-validation are predictive of root-mean-square errors of compounds tested
      after the model was built.

PMID- 22385390
TI  - Cervical dilation as a predictor of pregnancy outcome following emergency
      cerclage.
AB  - OBJECTIVE: To determine whether cervical dilation at the time of physical
      examination indicated cerclage placement can predicts latency and gestational age
      at delivery. METHODS: A retrospective cohort study of all women who underwent
      physical examination indicated cerclage placement from 1996 to 2011 at Duke
      University Hospital (DUH) was performed. Physical examination indicated cerclage
      was defined as cerclage placement after 16 weeks in women with a cervical length
      of less than 2.5 cm and/or cervical dilation greater than or equal to 1 cm at
      time of procedure. Subjects were divided into two groups depending on cervical
      dilation at time of procedure (2 cm, <2 cm) for comparison. A multivariate linear
      regression model for the outcome gestational age of delivery was constructed,
      controlling for confounding variables. RESULTS: A total of 110 women with
      complete data were available for analysis. Median gestational age at cerclage
      placement was similar between the two groups (20.3 vs. 20.3 weeks, p = 0.8).
      Women with cervical dilatation >= 2 cm dilation delivered at an earlier median
      gestational age than women with cervical dilation <2 cm (27.0 vs. 35.6 weeks, p <
      0.001). Cervical dilation at the time of cerclage placement independently
      predicted gestational age at delivery while controlling for use of intracervical
      Foley balloon catheter for membrane reduction, cerclage suture type, history of
      prior preterm birth, race, insurance status, and tobacco use. CONCLUSIONS: Women
      who receive a rescue cerclage are more likely to deliver at an earlier
      gestational age when cervical dilation is >= 2 cm at the time of procedure.

PMID- 22385391
TI  - Toward single-DNA electrochemical biosensing by graphene nanowalls.
AB  - Graphene oxide nanowalls with extremely sharp edges and preferred vertical
      orientation were deposited on a graphite electrode by using electrophoretic
      deposition in an Mg(2+)-GO electrolyte. Using differential pulse voltammetry
      (DPV), reduced graphene nanowalls (RGNWs) were applied for the first time, in
      developing an ultra-high-resolution electrochemical biosensor for detection of
      the four bases of DNA (G, A, T, and C) by monitoring the oxidation signals of the
      individual nucleotide bases. The extremely enhanced electrochemical reactivity of
      the four free bases of DNA, single-stranded DNA, and double-stranded DNA (dsDNA)
      at the surface of the RGNW electrode was compared to electrochemical performances
      of reduced graphene nanosheet (RGNS), graphite, and glassy carbon electrodes. By
      increasing the number of DPVs up to 100 scans, the RGNW electrode exhibited an
      excellent stability with only 15% variation in the oxidation signals, while for
      the RGNS electrode no detectable signals relating to T and C of 0.1 MUM dsDNA
      were observed. The linear dynamic detection range of the RGNW electrode for dsDNA
      was checked in the wide range of 0.1 fM to 10 mM, while for the RGNS electrode,
      it was from 2.0 pM to <10 mM. The lower limits of dsDNA detection of the RGNW and
      RGNS electrodes were estimated as 9.4 zM (~5 dsDNA/mL) and 5.4 fM, respectively.
      The RGNWs were efficient in label-free detection of single nucleotide
      polymorphisms of 20 zM oligonucleotides (~10 DNA/mL) having a specific sequence.
      Therefore, the RGNWs can effectively contribute to the development of ultra-high
      sensitive electrochemical biosensors with single-DNA resolutions.

PMID- 22385392
TI  - Post-operative pain treatment in Denmark from 2000 to 2009: a nationwide
      sequential survey on organizational aspects.
AB  - BACKGROUND: In Denmark, the first acute pain service (APS) was introduced in
      1993. An important objective became to facilitate implementation of accelerated
      post-operative rehabilitation programmes (ACC) in selected procedures in
      abdominal, gynaecological and orthopaedic surgery. Therefore, it is of
      considerable interest to study the association between the developments of post
      operative pain management and the ACC by sequential analyses from 2000 to 2009.
      METHODS: In 2000, 2003, 2006 and 2009, a questionnaire was mailed to all Danish
      anaesthesiology departments. The headings of the questionnaire were demographics
      of responder departments, resources allocated to pain management methods, quality
      assessment methods, research activities and implementation of ACC. RESULTS: The
      responder rates varied between 80% and 94% (mean 88%) representing a mean number
      of anaesthetics of 340.000 per year. The number of APSs in the study period
      varied in university hospitals between 52% and 71% (P = 0.01), regional hospitals
      between 8% and 40% (P < 0.01), and local hospitals between 0% and 47% (P < 0.01).
      The prevalences of departments actively engaged in ACC were 40% in 2000, 54% in
      2003, 73% in 2006 and 80% in 2009 (P < 0.01). CONCLUSIONS: The study, spanning
      nearly a decade, illustrates that following an increase in number of APSs from
      2000 to 2006, followed by a significant decline, a steadily increasing number of
      departments implemented ACC.

PMID- 22385393
TI  - For the sequence YKGQ, the turn and extended conformational forms are separated
      by small barriers and the turn propensity persists even at high temperatures:
      implications for protein folding.
AB  - The folding of the sequence (21)DTVKLMYKGQPMTFR(35) from staphylococcal nuclease
      into a beta-hairpin, nucleated by the turn region YKGQP, is known to be an early
      folding event. With YKGQ being the shortest sequence for a beta-turn model and in
      view of its importance to the folding of staphylococcal nuclease, we investigated
      the thermodynamics of turn formation at a range of temperatures from 280 to 380
      K, with a regular interval of 10 K. Eleven independent molecular dynamics
      simulations (under NPT conditions) were performed using the GROMACS package of
      programs and the OPLS-AA/L all-atom force field, each for a time period of 1 MUs.
      Turn formation is supported by enthalpy at lower temperatures, while entropy
      supports it at higher temperatures. There are modest free energy barriers between
      turn and extended conformational ensembles. The turn propensity persists even at
      elevated temperatures. The role of proline in driving the turn formation has been
      re-examined, and it is inferred that the absence of proline does not affect turn
      propensity.

PMID- 22385394
TI  - Cytomegalovirus disease and infection in lung transplant recipients in the
      setting of planned indefinite valganciclovir prophylaxis.
AB  - BACKGROUND: The optimal method of both predicting and preventing cytomegalovirus
      (CMV) disease in lung transplant recipients remains unclear. In particular, the
      most appropriate duration of CMV prophylaxis post transplant is unresolved. We
      report herein our experience with a planned indefinite regimen of valganciclovir
      prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage
      (BAL) fluid. METHODS: We performed a single-center observational study with both
      prospective and retrospective components. The included patients (n = 128)
      received a planned regimen of indefinite valganciclovir prophylaxis post
      transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time
      polymerase chain reaction assay for detection of CMV in BAL was prospectively
      performed over a 1-year period. Clinical data were reviewed retrospectively;
      median follow-up was 24.8 months (range 1-93 months). RESULTS: Sixty-five
      patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or
      permanently, with a primary cause of mild leukopenia. Six cases of CMV disease
      were identified (4.7%), with no significant difference between those who were on
      continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However,
      those who discontinued prophylaxis showed an increased incidence of laboratory
      detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did
      not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3%
      other serotypes; P = ns). Three patients (2.3%) developed valganciclovir
      resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly
      more sensitive than shell vial culture. However, BAL CMV viral load was not
      predictive of subsequent disease development. CONCLUSIONS: Extended
      valganciclovir prophylaxis for all lung transplant recipients led to a low
      incidence of CMV disease and resistance. In such low-incidence populations,
      routine quantitation of CMV in BAL did not confer significant clinical benefit
      over non-quantitative methods in prediction of CMV disease onset.

PMID- 22385395
TI  - Association of angiotensin-converting enzyme insertion/deletion gene polymorphism
      with idiopathic nephrotic syndrome susceptibility in children: an updated meta
      analysis.

PMID- 22385396
TI  - Sida rhomboidea.Roxb aqueous extract down-regulates in vivo expression of
      vascular cell adhesion molecules in atherogenic rats and inhibits in vitro
      macrophage differentiation and foam cell formation.
AB  - The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract
      in ameliorating experimental atherosclerosis using in vitro and in vivo
      experimental models. Atherogenic (ATH) diet fed rats recorded significant
      increment in the serum total cholesterol (TC), triglycerides (TG), low-density
      lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL),
      markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along
      with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an
      increased susceptibility of LDL isolated from ATH rats to undergo copper mediated
      oxidation. These set of changes were minimized by simultaneous co-supplementation
      of SR extract to ATH diet fed rats. Histopathology of aorta and
      immunolocalization studies recorded pronounced atheromatous plaque formation,
      vascular calcification, significant elastin derangements and higher expression of
      macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and
      p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of
      atheromatous plaque formation, calcium deposition, distortion/defragmentation of
      elastin and accumulation of macrophages along with lowered expression of VCAM-1
      and P-selectin compared to ATH rats. Further, monocyte to macrophage
      differentiation and in vitro foam cell formation were significantly attenuated in
      presence of SR extract. In conclusion, SR extract has the potency of controlling
      experimental atherosclerosis and can be used as promising herbal supplement in
      combating atherosclerosis.

PMID- 22385397
TI  - Has the procedure of choice for chronic pilonidal sinus disease finally been
      found?

PMID- 22385400
TI  - Thermal rearrangements of 1-ethynyl-2-methylcyclopropane: a computational study.
AB  - In this research, a comprehensive theoretical investigation of the thermal
      rearrangements of 1-ethynyl-2-methylcyclopropane is carried out employing density
      functional theory (DFT), with the B3LYP functional, and high-level ab initio
      methods, such as the complete active space self-consistent field (CASSCF),
      multireference second-order Moller-Plesset perturbation theory (MRMP2), and
      coupled-cluster singles and doubles with perturbative triples [CCSD(T)]. In all
      computations Pople's polarized triple-zeta split valence basis set, 6-311G(d,p),
      is utilized. The potential energy surface (PES) for the relevant system is
      explored to provide a theoretical account of the experiments by Hopf, Ellis and
      Frey, Huntsman et al., and Berson. The computational results herein on the target
      system show that the thermal aromatization reaction does not proceed via
      conversion of 1,2,5-hexatriene (2) to 1,3,5-hexatriene (10a) as proposed by Hopf.
      Indeed, the reaction proceeds via conversion of 5 and 6 to bicyclo[3.1.0]hexene
      (9) as suggested by Huntsman et al.

PMID- 22385398
TI  - Differences in prescription rates and odds ratios of antidepressant drugs in
      relation to individual hormonal contraceptives: a nationwide population-based
      study with age-specific analyses.
AB  - OBJECTIVES: To examine, among young women, the association of individual hormonal
      contraceptives, within two broad groupings, with antidepressant therapy. METHODS:
      In a nationwide register-based study, we examined the prescription rates of
      antidepressant drugs in relation to individual combined hormonal and progestin
      only contraceptives among Swedish women aged 16-31 years (N = 917,993). Drug data
      were obtained from the Swedish Prescribed Drug Register for the period 1 July
      2005-30 June 2008. Data on the total population of women aged 16-31 in 2008 were
      obtained from the Total Population Register of Statistics Sweden. The proportion
      of women using both hormonal contraception and antidepressants, and odds ratios
      (ORs) for antidepressant use for hormonal contraceptive users versus non-users,
      were calculated, the latter by logistic regression, for each formulation.
      RESULTS: The highest antidepressant OR in all age groups, particularly in the 16
      19 years age group, related to medroxyprogesterone-only, followed by etonogestrel
      only, levonorgestrel-only and ethinylestradiol/norelgestromin formulations. Oral
      contraceptives containing ethinylestradiol combined with lynestrenol or
      drospirenone had considerably higher ORs than other pills. ORs significantly
      lower than 1 were observed when ethinylestradiol was combined with
      norethisterone, levonorgestrel or desogestrel. CONCLUSION: The association
      between use of hormonal contraceptives and antidepressant drugs varies
      considerably within both the combined hormonal contraceptive and the progestin
      only groups.

PMID- 22385401
TI  - Modelling bacterial transmission in human allergen-specific IgE sensitization.
AB  - AIMS: The impact of bacterial transmission from mother to child on human allergy
      development is poorly understood. The aim of the present work was therefore to
      use a temporal collected dataset of 117 mothers and their children to model the
      potential effect of mother-to-child bacterial transmission on allergy (IgE)
      sensitization. METHODS AND RESULTS: We have recently shown a negative IgE
      correlation to high Escherichia coli levels until the age of 1 year, with a shift
      to positive correlation to high Bacteroides fragilis levels at the age of 2. In
      the present work, we used the previous published data to model the persistence
      and interaction effects of E. coli and B. fragilis with respect to IgE
      sensitization. Temporal modelling was made by first defining a stochastic model
      for sensitization state based on Markov chains and regression tree analyses.
      Subsequent simulations were used to determine the impact of mother-to-infant
      bacterial transmission. The regression tree analyses showed that E. coli
      colonization within 4 days was negatively correlated to sensitization, while lack
      of E. coli colonization at day 4 combined with B. fragilis colonization after 4
      months was positively correlated. With Markov chain analyses, we found that E.
      coli was highly persistent in infants until the age of 4 months, while the
      persistence of B. fragilis increased with age. CONCLUSIONS: Simulations showed
      that the mother's bacterial composition correlated significantly to the child's
      IgE sensitization state at the age of 2 years. High E. coli and low B. fragilis
      levels in the mother were negatively correlated, while low E. coli and high B.
      fragilis were positively correlated to IgE. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Our results support that allergy could partly be communicable, being transferred
      from mother to infant through the gut microbiota.

PMID- 22385402
TI  - Psoriasis and physical activity: a review.
AB  - Psoriasis is a common, chronic inflammatory skin disease that can cause
      significant discomfort and impairment to quality of life. Recent research
      indicates that individuals with moderate-to-severe psoriasis are likely at
      greater risk for chronic cardiometabolic co-morbidities such as cardiovascular
      disease, type 2 diabetes, obesity and metabolic syndrome. Physical activity can
      be an effective primary and adjunctive treatment for these maladies in other
      populations. Unfortunately, only a limited number of studies have examined
      physical activity in psoriasis, which are limited by poor design and lack of
      validated physical activity assessment methodologies. A variety of data suggest
      shared physiologic pathways between physical activity, psoriasis, and psoriasis
      cardiometabolic co-morbidities. Increased adiposity, inflammation, oxidative
      stress, adhesion molecules and lipids are physiologically linked to psoriasis,
      the risk of psoriasis cardiometabolic co-morbidities, and low levels of physical
      activity. In addition, epigenetic pathways are involved in psoriasis and could be
      influenced by physical activity. The physical and psychosocial impairments common
      in psoriasis may make it difficult to participate in regular physical activity,
      and future studies should aim to determine if physical activity interventions
      improve functioning and reduce co-morbidities in psoriasis.

PMID- 22385403
TI  - Biologic rheumatoid arthritis therapies: do we need more comparative
      effectiveness data?
AB  - Rheumatoid arthritis (RA) affects an estimated 1.3 million Americans and is a
      complex inflammatory disease associated with synovitis and joint destruction. The
      development of biologic disease-modifying anti-rheumatic drugs (DMARDs) that
      target specific mediators of inflammation has led to several highly successful
      therapies for the treatment of RA. The imperfect efficacy of biologic DMARDs has
      resulted in the absence of clear guidelines on how biologic DMARDs should be used
      in the clinic to optimize treatment of RA patients. This makes it imperative that
      better data be available to physicians and RA patients about the comparative
      effectiveness of different biologic DMARDs. Prior to 2008, there were no
      randomized trials comparing biologic DMARDs for the treatment of RA. Since then,
      there have been published studies that directly compared biologic DMARDs for the
      treatment of RA, and several studies that estimated the relative efficacy of
      different biologic DMARDs by comparing published results of studies that included
      treatment of RA patients with biologic DMARDs who had previously experienced an
      inadequate response to methotrexate or tumor necrosis factor (TNF) antagonists.
      There are two recent studies that directly compared biologic DMARDs with optimal
      combinations of oral DMARDs and these are important because there are significant
      differences in costs and side effects between oral and biologic DMARDs. Among the
      studies that directly compared biologic DMARDs, it has been reported that RA
      patients who fail a TNF antagonist have a higher response rate (based on disease
      activity score [DAS28] measurements) to treatment with rituximab as compared with
      another TNF antagonist. In addition, in the ATTEST trial, the investigators found
      that, for RA patients with an inadequate response to methotrexate, treatment with
      abatacept versus infliximab resulted in response rates that were roughly equal.
      There are also several head-to-head studies of biologic DMARDs that are currently
      enrolling or about to enroll RA subjects. Pharmaceutical companies have taken
      more interest in comparative effectiveness studies, in part due to the emphasis
      that has been placed on this type of research by the US federal government and
      associated organizations including the Patient-Centered Outcomes Research
      Institute (PCORI). Therefore, while there is currently a relative lack of
      comparative effectiveness research to inform clinical decisions about biologic
      DMARDs for RA patients, it appears likely that there will be wider availability
      of such data in the near future.

PMID- 22385404
TI  - Targeting the epidermal growth factor receptor in solid tumor malignancies.
AB  - The epidermal growth factor receptor (EGFR) is over-expressed, as well as
      mutated, in many types of cancers. In particular, the EGFR variant type III
      mutant (EGFRvIII) has attracted much attention as it is frequently and
      exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have been
      proposed as valid targets in many cancer therapy settings. Different strategies
      have been developed in order to either inhibit EGFR/EGFRvIII activity or to
      ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors
      include monoclonal antibodies (mAbs) that bind to the extracellular part of EGFR,
      blocking the binding sites for the EGFR ligands, and intracellular tyrosine
      kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase
      domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been
      used in different settings to deliver lethal agents to the EGFR/EGFRvIII-positive
      cells; among these are radio-labelled mAbs and immunotoxins. This article reviews
      the current status and efficacy of EGFR/EGFRvIII-targeted therapies.

PMID- 22385405
TI  - Hyaluronic acid for the treatment of osteoarthritis in all joints except the
      knee: what is the current evidence?
AB  - BACKGROUND: The use of intra-articular hyaluronic acid (HA) is a well known
      treatment in patients with knee osteoarthritis (OA). In other joints, less
      evidence is available about the efficacy of treatment with intra-articular HA. HA
      is also used intra-articularly in the metatarsophalangeal-1 joint, the ankle, the
      hip, the sacroiliac joint, the facet joints, the carpometacarpal-1 joint, the
      shoulder and the temporo-mandibular joint. In this systematic review we include
      all prospective studies about the effects of intra-articular HA in the above
      mentioned joints. Its use in the knee joint, however, will be discussed in a
      separate article in this journal. METHODS: A systematic review was conducted
      using databases including MEDLINE, Cochrane Database of Systematic Reviews,
      Cochrane Clinical Trial Register, and EMBASE. RESULTS: After performing a solid
      systematic review using a rigid methodology and trying to pool the outcomes of
      different studies, we noticed that, compared with baseline, there is statistical
      evidence for a positive effect of intra-articular HA. However, there is limited
      evidence HA is superior to placebo and no evidence that intra-articular HA is
      better than corticosteroids or other conservative therapies. CONCLUSION: Our
      recommendation for future research is that one should focus on adequately powered
      randomized trials comparing HA treatment with other types of intra-articular or
      conservative treatment. We think it is useless to further perform and publish
      (large) non-comparative prospective studies about the use of HA in the treatment
      of problems caused by OA. It is well perceived that HA exerts positive effects in
      the treatment of OA, but up to now there is no (strong) evidence available that
      HA is superior to other treatments of OA such as corticosteroids, physiotherapy
      or other conservative measures.

PMID- 22385406
TI  - How much are biosimilars used in southern Italy?: a retrospective analysis of
      epoetin utilization in the local health unit of Messina in the years 2010-2011.
AB  - BACKGROUND: Epoetins are one of the three biologics for which biosimilars are
      available in Italy. So far, there is a lack of Italian national/regional
      longitudinal data about epoetin use. OBJECTIVE: The aim of this study was to
      evaluate the prescribing pattern of epoetins (reference products and biosimilars)
      in a Local Health Unit (LHU) of Southern Italy in recent years. METHODS: A
      retrospective drug utilization study was conducted during the period 1 January
      2010 - 31 May 2011. The data source was the dispensing database of the Messina
      LHU, which contains anonymized data about dispensed drugs (including epoetins)
      that are prescribed by specialists to the residents in the catchment area.
      Indication of use and prescribed dosage of epoetins were derived by the
      therapeutic plans filled in by specialists and linked to drug dispensing records.
      Prevalence of epoetin use in the province of Messina (653 810 inhabitants) in
      2010 was calculated. Furthermore, frequency analyses by sex, age, indication of
      use of epoetin users, as well as measurement of volume of use (defined daily dose
      [DDD]/1000/day) and expenditure of epoetins in 2010 were also performed. Analysis
      of the switching pattern between different reference products and biosimilar
      epoetins was performed. RESULTS: Overall, 4288 patients were treated with
      epoetins during the study period (mean age  +/- SD: 74.2 +/- 13.7; females: 52%).
      Darbepoetin alpha and reference product epoetin alpha accounted overall for 79.8%
      of epoetin users, while biosimilars of epoetin alpha accounted for 0.9%. Among
      1247 epoetin users for whom the therapeutic plan was revised, 1065 (85.4%) were
      treated because of anemia due to chronic kidney disease and 158 (12.6%) because
      of chemotherapy-induced anemia. In 2010, prevalence of epoetin use was 5.5 (95%
      CI 5.3, 5.7) per 1000 inhabitants in the province of Messina. The volume of use
      and related expenditure for epoetins was 3.58 DDD/1000 inhabitants/day and Euro 5
      572 457 (about Euro 8.50 per capita/day) in 2010. Switching between different
      epoetins was very frequent (21.8% of users) but switching from reference products
      to biosimilars was very rare. CONCLUSIONS: Epoetins are frequently dispensed to
      residents in the province of Messina, mainly for the treatment of chronic kidney
      disease-related anemia, with a relevant impact on the pharmaceutical expenditure
      covered by the National Health System. Use of biosimilar products is very low in
      both naive patients and in those who switch from other reference product
      epoetins.

PMID- 22385407
TI  - DTaP(5)-IPV-Hib Vaccine (Pediacel): profile report.

PMID- 22385408
TI  - Clinical relevance of botulinum toxin immunogenicity.
AB  - Botulinum toxin type A is a 150 kD protein produced by Clostridium botulinum,
      which exists in a complex with up to six additional proteins. The ability of
      botulinum toxin to inhibit acetylcholine release at the neuromuscular junction
      has been exploited for use in medical conditions characterized by muscle
      hyperactivity. As such, botulinum toxin is widely recommended by international
      treatment guidelines for movement disorders and it has a plethora of other
      clinical and cosmetic indications. The chronic nature of these conditions
      requires repeated injections of botulinum toxin, usually every few months.
      Multiple injections can lead to secondary treatment failure in some patients that
      may be associated with the production of neutralizing antibodies directed
      specifically against the neurotoxin. However, the presence of such antibodies
      does not always render patients non-responsive. The reported prevalence of
      immunoresistance varies greatly, depending on factors such as study design and
      treated indication. This review presents what is currently known about the
      immunogenicity of botulinum toxin and how this impacts upon patient non-response
      to treatment. The complexing proteins may act as adjuvants and stimulate the
      immune response. Their role and that of neutralizing and non-neutralizing
      antibodies in the response to botulinum toxin is discussed, together with an
      assessment of current neutralizing antibody measurement techniques. Botulinum
      toxin preparations with different compositions and excipients have been
      developed. The major commercially available preparations of botulinum toxin are
      Botox (onabotulinumtoxin A; Allergan, Inc., Ireland), Dysport (abobotulinumtoxin
      A; Ipsen Ltd, UK), and Xeomin (incobotulinumtoxin A; botulinum toxin type A [150
      kD], free from complexing proteins; NT 201; Merz Pharmaceuticals GmbH, Germany).
      The new preparations of botulinum toxin aim to minimize the risk of
      immunoresistance in patients being treated for chronic clinical conditions.

PMID- 22385409
TI  - Expression of bone morphogenetic protein 2, 4, 5, and 7 correlates with
      histological activity of otosclerotic foci.
AB  - CONCLUSION: This study is the first to establish that bone morphogenetic protein
      5 (BMP5) plays a role in the pathogenesis of otosclerosis. These results confirm
      that elevated expression levels of BMPs, members of the transforming growth
      factor (TGF)-beta superfamily, contribute to the pathologically increased bone
      turnover in early, active stages of otosclerosis. OBJECTIVES: Otosclerosis is a
      complex bone remodeling disorder of the otic capsule, which might be
      characterized by increased expression of different types of BMPs. TGF-beta and
      BMP are both members of the TGF-beta superfamily and play a critical role in bone
      resorption and new bone formation. It has been suggested that BMP and its
      receptors may be involved in the pathologically increased bone turnover observed
      in otosclerosis. METHODS: Fifty-one otosclerotic and 16 non-otosclerotic
      ankylotic stapes footplates were histologically analyzed: conventional
      hematoxylin-eosin staining and BMP2, 4, 5, and 7specific immunofluorescent assays
      were performed. Cortical bone fragments (n = 35) and incus specimens (n = 6) were
      used as negative controls. RESULTS: Active otosclerosis (n = 39) was
      characterized by increased expression of BMP2, 4, 5, and 7. Inactive cases of
      otosclerosis (n = 12) were characterized by negative immunoreaction for BMPs. Non
      otosclerotic stapes specimens (n = 16) and negative controls (n = 41) showed
      negligible BMP expression. The BMP expression pattern showed a strong correlation
      with the histological activity of otosclerosis.

PMID- 22385410
TI  - Diffuse pleural mesothelioma with epithelioid and angiosarcomatous components--a
      hitherto undescribed pattern of differentiation.

PMID- 22385411
TI  - Current antenatal management of monoamniotic twins: a survey of maternal-fetal
      medicine specialists.
AB  - OBJECTIVE: To assess current management of monoamniotic (MA) twins by US maternal
      fetal medicine providers. METHODS: We conducted a mailed survey to members of the
      Society for Maternal-Fetal Medicine regarding fetal surveillance practices and
      preferred gestational age (GA) for elective delivery with respect to MA twins.
      RESULTS: Responses from 837 (43%) were received with most (83.9%) recommending
      elective admission for inpatient monitoring, 53.5% favoring 26-28 weeks as
      earliest GA for admission and 75% performing intermittent fetal monitoring (of
      these 81% monitored 2-3 times/day). Respondents in practice less than 10 years
      were less likely to use outpatient management (p < 0.05). Median GA for elective
      delivery was 34 weeks but was higher for those who favored outpatient management,
      admitted >28 weeks, and were private practitioners (p < 0.05). CONCLUSIONS:
      Despite a paucity of evidence, most practitioners admit MA to perform daily
      intermittent fetal monitoring and deliver at 34 weeks. Antenatal management
      protocols may also influence timing of delivery. Due to their rarity, a national
      registry may be a better tool to analyze the outcomes of these pregnancies.

PMID- 22385413
TI  - Dynamic behavior of water droplets on solid surfaces with pillar-type
      nanostructures.
AB  - In the present study, we investigated the static and dynamic behavior of water
      droplets on solid surfaces featuring pillar-type nanostructures by using
      molecular dynamics simulations. We carried out the computation in two stages. As
      a result of the first computational stage, an initial water cube reached an
      equilibrium state at which the water droplet showed different shapes depending on
      the height and the lateral and gap dimensions of the pillars. In the second
      computational stage, we applied a constant body force to the static water droplet
      obtained from the first computational stage and evaluated the dynamic behavior of
      the water droplet as it slid along the pillar-type surface. The dynamic behavior
      of the water droplet, which could be classified into three different groups,
      depended on the static state of the water droplet, the pillar characteristics
      (e.g., height and the lateral and gap dimensions of the pillars), and the
      magnitude of the applied body force. We obtained the advancing and receding
      contact angles and the corresponding contact angle hysteresis of the water
      droplets, which helped classify the water droplets into the three different
      groups.

PMID- 22385412
TI  - Identification and characterization of a GDSL lipase-like protein that catalyzes
      the ester-forming reaction for pyrethrin biosynthesis in Tanacetum
      cinerariifolium- a new target for plant protection.
AB  - Although natural insecticides pyrethrins produced by Tanacetum cinerariifolium
      are used worldwide to control insect pest species, little information is known of
      their biosynthesis. From the buds of T. cinerariifolium, we have purified a
      protein that is able to transfer the chrysanthemoyl group from the coenzyme A
      (CoA) thioester to pyrethrolone to produce pyrethrin I and have isolated cDNAs
      that encode the enzyme. To our surprise, the active principle was not a member of
      a known acyltransferase family but a member of the GDSL lipase family. The
      recombinant enzyme (TcGLIP) was expressed in Escherichia coli and displayed the
      acyltransferase reaction with high substrate specificity, recognized the absolute
      configurations of three asymmetric carbons and also showed esterase activity. A
      S40A mutation in the Block I domain reduced both acyltransferase and esterase
      activities, which suggested an important role of this serine residue in these two
      activities. The signal peptide directed the localization of TcGLIP::enhanced
      green fluorescent protein (EGFP) fusion, as well as EGFP, to the extracellular
      space. High TcGLIP gene expression was observed in the leaves of mature plants
      and seedlings as well as in buds and flowers, a finding that was consistent with
      the pyrethrin I content in these parts. Expression was enhanced in response to
      wounding, which suggested that the enzyme plays a key role in the defense
      mechanism of T. cinerariifolium.

PMID- 22385414
TI  - Parsimonious prediction of Wechsler Memory Scale, Fourth Edition scores:
      immediate and delayed memory indexes.
AB  - Research on previous versions of the Wechsler Memory Scale (WMS) found that index
      scores could be predicted using a parsimonious selection of subtests (e.g.,
      Axelrod & Woodard, 2000). The release of the Fourth Edition (WMS-IV) requires a
      reassessment of these predictive formulas as well as the use of indices from the
      California Verbal Learning Test-II (CVLT-II). Complete WMS-IV and CVLT-II data
      were obtained from 295 individuals. Six regression models were fit using WMS-IV
      subtest scaled scores-Logical Memory (LM), Visual Reproduction (VR), and Verbal
      Paired Associates (VPA)-and CVLT-II substituted scores to predict Immediate
      Memory Index (IMI) and Delayed Memory Index (DMI) scores. All three predictions
      of IMI significantly correlated with the complete IMI (r = .92 to .97). Likewise,
      predicted DMI scores significantly correlated with complete DMI (r = .92 to .97).
      Statistical preference was indicated for the models using LM, VR, and VPA, in
      which 97% and 96% of the cases fell within two standard errors of measurement
      (SEMs) of full index scores, respectively. The present findings demonstrate that
      the IMI and DMI can be reliably estimated using two or three subtests from the
      WMS-IV, with preference for using three. In addition, evidence suggests little to
      no improvement in predictive accuracy with the inclusion of CVLT-II indices.

PMID- 22385415
TI  - Diclofenac-tramadol vs. diclofenac-acetaminophen combinations for pain relief
      after caesarean section.
AB  - BACKGROUND: We compared the analgesic efficacy of diclofenac-acetaminophen
      combination with diclofenac-tramadol combination to optimize multimodal post
      operative analgesia in women undergoing caesarean section. METHODS: In this
      randomized, double-blind, parallel-group controlled trial, 204 women undergoing
      caesarean section under spinal anaesthesia with bupivacaine received rectal
      suppository diclofenac 100 mg (8 hourly till 24 h) plus either intravenous
      acetaminophen (1 g 6 hourly) or tramadol (75 mg 6 hourly) post-operatively. The
      primary outcome measure was the summed pain intensities during the entire
      observation period, calculated as the sum of time-weighted pain intensity scores
      as an area under the curve (AUC). Secondary outcome was the use of rescue
      analgesic, administered if the patient's numeric rating scale (NRS) scores >=  4.
      RESULTS: The overall pain score for the entire observation period measured as AUC
      was significantly lower in the diclofenac-tramadol group. However, diclofenac
      tramadol combination produced Bonferroni-corrected statistically significant
      lower NRS pain scores only on movement at 24 h. Rescue analgesic consumption was
      comparable between the groups (13% vs. 12%, P = 0.872). Overall, the pain scores
      were low in both of the groups across various time intervals (median NRS scores 0
      2 for pain both at rest and on movement), indicating satisfactory pain control in
      both groups. Side effects were few and comparable, except nausea (significantly
      more in tramadol group than acetaminophen group, 15% vs. 2%, P = 0.001).
      CONCLUSION: Both diclofenac-tramadol and diclofenac-acetaminophen combinations
      can achieve satisfactory post-operative pain control in women undergoing
      caesarean section. The diclofenac-tramadol combination was overall more
      efficacious but associated with higher incidence of post-operative nausea.

PMID- 22385417
TI  - Analyzing protein-protein interaction networks.
AB  - The advent of the "omics" era in biology research has brought new challenges and
      requires the development of novel strategies to answer previously intractable
      questions. Molecular interaction networks provide a framework to visualize
      cellular processes, but their complexity often makes their interpretation an
      overwhelming task. The inherently artificial nature of interaction detection
      methods and the incompleteness of currently available interaction maps call for a
      careful and well-informed utilization of this valuable data. In this tutorial, we
      aim to give an overview of the key aspects that any researcher needs to consider
      when working with molecular interaction data sets and we outline an example for
      interactome analysis. Using the molecular interaction database IntAct, the
      software platform Cytoscape, and its plugins BiNGO and clusterMaker, and taking
      as a starting point a list of proteins identified in a mass spectrometry-based
      proteomics experiment, we show how to build, visualize, and analyze a protein
      protein interaction network.

PMID- 22385416
TI  - Understanding the complexity of gammadelta T-cell subsets in mouse and human.
AB  - gammadelta T cells are increasingly recognized as having important functional
      roles in a range of disease scenarios such as infection, allergy, autoimmunity
      and cancer. With this has come realization that gammadelta cells are not a
      homogeneous population of cells with a single physiological role. Instead, ever
      increasing complexity in both phenotype and function is being ascribed to
      gammadelta cell subsets from various tissues and locations, and in both mouse and
      human. Here, we review this complexity by describing how diverse gammadelta cell
      subsets are generated in the murine thymus, and how these events relate to
      subsequent gammadelta subset function in the periphery. We then review the two
      major gammadelta cell populations in human, highlighting the several similarities
      of Vdelta1(+)  cells to certain murine gammadelta subsets, and describing the
      remarkable functional plasticity of human Vdelta2(+)  cells. A better
      understanding of this spectrum of gammadelta cell phenotypes should facilitate
      more targeted approaches to utilise their tremendous functional potential in the
      clinic.

PMID- 22385420
TI  - Recovery: past progress and future challenges.

PMID- 22385418
TI  - Controlled oxygen reperfusion protects the lung against early ischemia
      reperfusion injury in cardiopulmonary bypasses by downregulating high mobility
      group box 1.
AB  - Restricting oxygen delivery during the reperfusion phase of cardiopulmonary
      bypass (CPB) protects the heart, but effects on lung ischemia reperfusion (IR) in
      CPB are unknown. We examined whether extracellular high mobility group box 1
      (HMGB1) mediated inflammation during early lung IR injury in CPB. Fourteen
      healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic
      arrest, followed by 90 minutes reperfusion. Following surgery, the animals were
      randomized into control (n = 7) or test (n = 7) groups. Control animals received
      a constant level of 80% FiO(2) during the entire procedure, and the test group
      received a gradual increase in FiO(2) during the first 25 minutes of reperfusion.
      In the test group, the FiO(2) was initiated at 40% and increased by 10% every 5
      minutes, to 80%. Histology, lung injury variables, HMGB1 expression, and
      inflammatory responses were assessed at baseline (T1) and at 25 minutes (T2) and
      90 minutes (T3) after starting reperfusion. Treatment with controlled oxygen
      significantly suppressed lung pathologies, lung injury variables, and
      inflammatory responses (all P < .001). After lung IR injury, HMGB1 mRNA and
      protein expressions were significantly decreased in the controlled oxygen group
      (all P < .001). Controlled oxygen reperfusion is protective in the early stages
      of lung IR injury in a canine CPB model, and this protection is linked to HMGB1
      downregulation.

PMID- 22385421
TI  - Recovery in Australia: marshalling strengths and living values.
AB  - Clear national policy now exists in Australia regarding recovery. Personal
      accounts of recovery often include reference to meaning, purpose and issues
      regarding identity. Personal strengths and expression of personal values are
      closely related to the development of meaning, purpose and a stable sense of
      self, resulting in a sense of wellbeing. These constructs fall under the research
      umbrella of positive psychology. By combining aspects of the recovery policy with
      evidence from the science of positive psychology there are increasing attempts to
      include strengths and values work with mental health staff and consumers. This
      paper describes how the collaborative recovery model (CRM) with its emphasis on
      strengths and values, draws on the emerging evidence based on positive
      psychology. CRM has now been implemented in non-government community services in
      each mainland state of Australia. Implementation issues of the CRM as one example
      of recovery-orientated service provision are then described. Potential barriers
      and facilitators of growth-based approaches such as CRM moving to government
      clinical services is then discussed. Recent national reviews of recovery
      measurement instruments are also summarized. Specific recommendations are then
      provided to further national implementation of recovery-orientated service
      provision in Australia.

PMID- 22385422
TI  - Recovery in Austria: mental health trialogue.
AB  - The active involvement of service users and relatives and friends is essential
      for the development of recovery-orientated mental health practice and research.
      However, accepting each other as equally entitled experts is still a challenge.
      In trialogue groups users, carers and friends and mental health workers meet
      regularly in an open forum that is located on 'neutral terrain' - outside any
      therapeutic, familial or institutional context - with the aim of discussing the
      experiences and consequences of mental health problems and ways forward.
      Trialogues offer new possibilities for gaining knowledge and insights and
      developing new ways of communicating beyond role stereotypes. They also function
      as the basis and starting point for trialogic activities on different levels,
      e.g. serving on quality control boards or teaching in trialogic teams, and
      different topics, e.g. a task force on stigma busting or a work group on trauma
      and psychosis. In German-speaking countries well over a hundred trialogue groups
      are regularly attended by altogether about 5,000 people. International interest
      and experiences are growing fast. Trialogues facilitate a discrete and
      independent form of acquisition and production of knowledge and drive relevant
      changes in forms of communication as well as in structures.

PMID- 22385423
TI  - Recovery in Canada: toward social equality.
AB  - This article reviews evolution of the recovery paradigm in Canadian mental
      health. We first trace the origins and development of the recovery concept
      through the literature, followed by an examination of how the recovery concept
      has been implemented in national and provincial mental health policy since
      publication of the 2006 Kirby Commission Report. Based on consultations with
      Canadian policymakers, and an examination of available policy documents, we
      explore how the dual theme of 'recovery' and 'well-being', adopted by the Mental
      Health Commission of Canada in its 2009 strategy: Toward Recovery and Well-being 
      A Framework For a Mental Health Strategy has subsequently played out in mental
      health policymaking at the provincial level. Findings reveal mixed support for
      recovery as a guiding principle for mental health reform in Canada. While
      policies in some provinces reflect widespread support for recovery, and strong
      identification with the aspirations of the consumer movement; other provinces
      have shifted to population-based, wellness paradigms that privilege evidence
      based services and professional expertise. The recognition of social equality for
      people who experience mental illness emerges as an important value in Canadian
      mental health policy, cutting across the conceptual divide between recovery and
      well-being.

PMID- 22385424
TI  - Recovery in England: transforming statutory services?
AB  - English mental health policy has explicitly supported a focus on recovery since
      2001. More recently, this has been elaborated through policy support for social
      inclusion, employment and well-being. We review several drivers for this
      political orientation, including a refocusing of the role of health services as a
      whole from treating illnesses to helping people to make the most of their lives,
      the shift to greater power for the individual, reflected in personal social care
      and personal health budgets, and the evidence informing clinical guidelines
      issued by the National Institute for Health and Clinical Excellence (NICE). A
      disjunction remains between policy and practice, with organizational policies
      espousing a recovery orientation and teams re-branding as 'recovery and support'
      teams, whilst pursuing clinical practices which prioritize symptomatic treatment
      rather than recovery support. The next phase of development in English statutory
      mental health services is therefore bridging this gap, through organizational
      transformation in mental health services towards a focus on recovery. We describe
      two funded initiatives to support this process of organizational transformation.
      The first (ImROC) is a national initiative to develop a pro-recovery
      organizational climate. The second (REFOCUS) is a multi-site cluster randomized
      controlled trial (ISRCTN02507940) investigating a team-level pro-recovery
      intervention.

PMID- 22385425
TI  - Recovery in Hong Kong: service user participation in mental health services.
AB  - This article provides an overview of mental health services (MHS) and the
      application of the recovery concept in Hong Kong, focusing on user participation.
      It presents stakeholders' views of the recovery movement in a round-table
      discussion format, demonstrating agreement that user participation merits more
      public and official attention. Some of the present difficulties with the movement
      are also reviewed. Social identity theory (SIT) is then analysed as a potentially
      useful framework for theorizing how service users' identities change as they
      become service providers. The paper then provides an overview of the current
      financial and political position of MHS, and identifies signs that the recovery
      approach is becoming accepted. It also addresses the cultural meanings of the
      concept, and sets out examples of its implementation in the health and social
      welfare sectors. Lastly, it summarizes the challenges facing service providers
      and users and concludes that as the recovery movement is still in its infancy in
      Hong Kong, more coordinated efforts are needed to establish the organizational
      support and policy framework, so that sustainable and evidence-based service
      provision can be achieved.

PMID- 22385426
TI  - Recovery in Israel: a legislative recovery response to the needs-rights paradox.
AB  - This paper uses the framework of the applied social science needs/rights antinomy
      to describe the efforts of Israel's mental health system in transforming a
      hospital-based orientation to services for individuals with a severe mental
      illness, to a community-based recovery orientation. On the one hand, a rationale
      for the provision of services to individuals with a severe mental illness that
      stresses these individuals' needs can justify the allocation of society's limited
      resources by referring to an objectively determinable set of psychiatric needs.
      However, this rationale may establish an inherent asymmetry between the adequate
      help provider and deficient help user. On the other hand, a rationale for
      providing psychiatric rehabilitation services that stresses the fundamental
      symmetry between the help provider and the help user is empowering, thus
      consistent with the recovery approach. However, this rationale does not provide a
      mechanism for negotiating the vague boundary between mental health and mental
      illness. Israel's mental health system has operationalized a policy that
      emphasizes rights as well as needs by legislating for a comprehensive set of
      rehabilitation services that individuals meeting the eligibility criteria may
      receive. This paper discusses this approach's achievements, challenges and
      implications for future policy, research, and practice.

PMID- 22385427
TI  - Recovery in New Zealand: an evolving concept?
AB  - Recovery was first officially promoted in New Zealand in 1998 and it became a key
      concept in mental health service development. Since the mid 2000s however,
      recovery has been on the wane in New Zealand, but the fundamental concepts within
      the term live on in two more recently adopted terms: whanau ora and well-being.
      He Korowai Oranga (Maori Health Strategy) defines whanau ora as families being
      supported to achieve health and well-being. The extended family is recognized as
      a source of strength, identity, security and support. Whanau ora is underpinned
      by Te Whare Tapa Wha, a well-being model that focuses on health being a balance
      between Taha Wairua (spiritual health), Taha Tinana (physical health), Taha
      Hinengaro (psychological health) and Taha Whanau (family health). New Zealanders
      are also using the term well-being, not just for the whole population but for
      people diagnosed with mental illness. The advantages of placing recovery into the
      larger well-being agenda are reduced discrimination and segregation of people
      with a diagnosis into a distinct population group, reduced association with
      medical and deficits approaches that can counter the recovery approach, and
      bypassing the dilution of the recovery approach that has occurred in traditional
      services.

PMID- 22385428
TI  - Recovery in Scotland: beyond service development.
AB  - Over the last ten years there has been significant activity related to the
      promotion and support of recovery in Scotland, much of it linked to the work of
      the Scottish Recovery Network. A range of government policies have consistently
      identified recovery as a guiding principle of both service design and mental
      health improvement efforts. New learning has been developed and shared, workforce
      competencies reviewed and training developed, and a range of national initiatives
      put in place. In Scotland, as elsewhere, these efforts have tended to focus
      primarily on ensuring that mental health services offer environments and
      practices that support personal recovery. While service improvement is crucial, a
      wider challenge is ensuring that opportunities and support for self-directed
      recovery are enhanced outside statutory services. Providing examples, this paper
      will look at the development of recovery in Scotland - including the work of the
      Scottish Recovery Network - and consider the potential for building on progress
      made by rebalancing efforts to support personal recovery, highlighting the
      importance of public attitudes and community-based learning approaches. We will
      also touch on the role of identity in personal recovery and consider cultural
      issues related to the promotion of recovery in Scotland.

PMID- 22385429
TI  - Recovery in the USA: from politics to peer support.
AB  - Efforts to transform the mental health service delivery system to a more consumer
      driven and recovery-orientated approach has its roots in a somewhat radical anti
      psychiatry and civil-rights movement dating back to the 1970s. This grass-roots
      effort gained momentum and credibility with Harding's landmark study published in
      1988 followed by the work of Anthony et al. from Boston University in beginning
      to define the term 'recovery'. In 1998 the Office of the US Surgeon General
      issued its first report on mental health, and this critical view of the
      shortcomings of the existing service system set the stage for the 2003
      President's New Freedom Commission and its recommendations for recovery
      orientated systems transformation. The recovery movement has evolved from a more
      radical view in the early days, to participatory involvement in systems, to
      returning to alternative models of care that are more independent. Now as more
      peer specialists work in systems, there is an increased emphasis on non-medical
      alternatives and the cycle continues. Regardless, recovery, self-determination,
      choice, etc. are always at the centre. This paper notes the interesting cycles of
      recovery-orientation and how they spin around the values/tenets of the movement's
      early roots.

PMID- 22385430
TI  - Airborne enteric micro-organisms and ammonia levels in diaper-changing rooms in
      kindergartens.
AB  - AIMS:   We evaluated risks associated with diaper changing in Finnish
      kindergartens where children were using either modern disposable paper or
      reusable cloth diapers. METHODS AND RESULTS:   We determined enteric micro
      organisms and ammonia in diaper-changing rooms in four kindergartens in autumn
      and winter in the ambient air. No coliphages were detected in the air. The
      numbers of faecal coliforms and enterococci in air were typically low regardless
      of whether the children used either paper or cloth diapers. Ammonia
      concentrations increased over the background level because of diaper changing.
      CONCLUSIONS:   The numbers of bacteria or coliphages are not expected to pose any
      high air hygiene risks, and increased ammonia air concentrations are unlikely to
      impair the health of staff or children when diapers are changed in modern
      kindergartens. However, increased ammonia gas concentrations indicate that some
      other diaper-related gas-phase emissions should be studied to understand better
      diaper-related health risks. SIGNIFICANCE AND IMPACT OF THE STUDY:   Modern
      reusable cloth baby diapers and the modern paper baby diapers used in this study
      are equally safe with respect to risks from airborne virus, bacteria or ammonia.

PMID- 22385431
TI  - Myositis due to the microsporidian Anncaliia (Brachiola) algerae in a lung
      transplant recipient.
AB  - Microsporidia are obligate intracellular parasites, more closely related to fungi
      than protozoa on molecular phylogenetic analysis, and are known to be a rare
      cause of opportunistic infection in immune compromised patients including human
      immunodeficiency virus-positive patients and solid organ transplant recipients.
      We report the first case to our knowledge of microsporidial myositis in a lung
      transplant recipient. He was 49 years old and had received a lung transplant in
      2000 for cystic fibrosis. He presented in 2009 with fevers, chronic diarrhea,
      myalgia, and pancytopenia, and developed progressive weakness and neurological
      symptoms before his death 35 days after hospital admission. Multiple
      investigations, including stool culture, rectal biopsy, colonoscopy,
      cerebrospinal fluid examination, bone marrow biopsy, lung biopsy, and
      bronchoalveolar lavage, failed to reveal a definite cause for the patient's
      deterioration. The diagnosis of microsporidial infection was made on post-mortem
      light microscopic examination of tissue sections of the tongue and deltoid
      muscle. Light microscopy diagnosed a microsporidial myositis, confirmed by
      transmission electron microscopy, which suggested that the organism was Brachiola
      species. The identity of the organism was confirmed by polymerase chain reaction
      as Brachiola algerae (recently renamed Anncaliia algerae). The case highlights
      the need to consider protozoal organisms in the differential diagnosis of myalgia
      and multisystemic infections in immune compromised patients.

PMID- 22385432
TI  - Factors influencing survival according to elapsed time in peritoneal dialysis
      patients.
AB  - The survival of patients undergoing peritoneal dialysis (PD) has improved over
      the past decade, but their mortality rate remains high. The aim of the current
      study was to identify correctable and uncorrectable factors influencing survival
      according to the elapsed time in patients undergoing PD. We retrospectively
      analyzed data from medical records of 118 patients who had undergone PD for >6
      months. We analyzed laboratory findings at three time points (point of PD
      initiation, 6-month point of PD and 3-month point prior to death or last follow
      up) during PD treatment and prescribed medications taken for >50% of the follow
      up period. Three-year survival group was younger, had lower prevalence rates of
      ischemic heart disease (p = 0.024) and heart failure (HF) (8.5% vs. 34.6%, p =
      0.003), higher serum albumin levels (albumin 2) at the 6-month point of PD, and
      higher serum albumin (albumin3) and creatinine (creatinine3) levels at the 3
      month point prior to death or last follow-up than nonsurvival group. Patients
      without underlying HF, patients treated with angiotensin-converting enzyme
      inhibitors or angiotensin II receptor blockers during the last 6 months (p =
      0.0042), and those having creatinine 3 >9.5 mg/dL (p = 0.0029), and albumin 2 (p
      = 0.0209) and albumin 3 >3.5 g/dL (p = 0.0003) showed significantly higher
      survival curves. HF and albumin 3 were found to be independent factors for 3-year
      survival and long-term survival, respectively, by the multivariate Cox regression
      model. In conclusion, HF was useful information for predicting 3-year survival,
      and low serum albumin levels according to elapsed time should be corrected for
      survival of PD patients.

PMID- 22385433
TI  - Lung function and skin prick test in wheat flour mill workers in Southwestern
      Iran.

PMID- 22385435
TI  - Comparative active-site mutation study of human and Caenorhabditis elegans
      thymidine kinase 1.
AB  - The first step for the intracellular retention of several anticancer or antiviral
      nucleoside analogues is the addition of a phosphate group catalysed by a
      deoxyribonucleoside kinase such as thymidine kinase 1 (TK1). Recently, human TK1
      (HuTK1) has been crystallized and characterized using different ligands. To
      improve our understanding of TK1 substrate specificity, we performed a detailed,
      mutation-based comparative structure-function study of the active sites of two
      thymidine kinases: HuTK1 and Caenorhabditis elegans TK1 (CeTK1). Specifically,
      mutations were introduced into the hydrophobic pocket surrounding the substrate
      base. In CeTK1, some of these mutations led to increased activity with
      deoxycytidine and deoxyguanosine, two unusual substrates for TK1-like kinases. In
      HuTK1, mutation of T163 to S resulted in a kinase with a 140-fold lower K(m) for
      the antiviral nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) compared with
      the natural substrate thymidine. The crystal structure of the T163S-mutated HuTK1
      reveals a less ordered conformation of the ligand thymidine triphosphate compared
      with the wild-type structure but the cause of the changed specificity towards AZT
      is not obvious. Based on its highly increased AZT activity relative to thymidine
      activity this TK1 mutant could be suitable for suicide gene therapy.

PMID- 22385436
TI  - Therapy for metastatic melanoma: the past, present, and future.
AB  - Metastatic melanoma is the most aggressive form of skin cancer with a median
      overall survival of less than one year. Advancements in our understanding of how
      melanoma evades the immune system as well as the recognition that melanoma is a
      molecularly heterogeneous disease have led to major improvements in the treatment
      of patients with metastatic melanoma. In 2011, the US Food and Drug
      Administration (FDA) approved two novel therapies for advanced melanoma: a BRAF
      inhibitor, vemurafenib, and an immune stimulatory agent, ipilimumab. The success
      of these agents has injected excitement and hope into patients and clinicians
      and, while these therapies have their limitations, they will likely provide
      excellent building blocks for the next generation of therapies. In this review we
      will discuss the advantages and limitations of the two new approved agents,
      current clinical trials designed to overcome these limitations, and future
      clinical trials that we feel hold the most promise.

PMID- 22385437
TI  - Percutaneous radiofrequency denervation in patients with contraindications for
      total hip arthroplasty.
AB  - Multiple comorbidities sometimes represent a contraindication for total hip
      arthroplasty (THA). Major symptoms of patients with hip pain include groin,
      thigh, and trochanteric pain. Groin and thigh pain arise from sensory branches of
      the obturator nerve, whereas trochanteric pain arises from sensory branches of
      the femoral nerve. Between January 2009 and October 2010, eighteen patients with
      chronic hip pain with several contraindications for THA were selected for a
      prospective study. Predenervation diagnosis was osteoarthritis in 16 patients and
      prolonged postoperative hip pain in 2 (1 THA, 1 Girdlestone). Hip joint pain was
      treated by percutaneous radiofrequency lesioning of the sensory branches of the
      obturator and femoral nerves. Six-month follow-up data revealed a statistically
      significant decrease in visual analog scale (VAS) scores and Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) scores, and a statistically
      significant increase of Harris Hip Score. Before radiofrequency and at 6-month
      follow-up, mean VAS scores were 9.52 (range, 7-10; standard deviation [SD], 0.79)
      and 6.35 (range, 3-10; SD, 2.17), respectively; mean Harris Hip Scores were 28.64
      (range, 19-41; SD, 6.98) and 43.88 (range, 23-71; SD, 16.38), respectively; and
      mean WOMAC scores were 75.70 (range, 92-59; SD, 9.70) and 63.70 (range, 78-44;
      SD, 11.37), respectively. All values were statistically significant (P<.05) for
      Student's t test and Wilcoxon signed-rank test. Eight patients reported >=50%
      pain relief at 6-month follow-up. No side effects were reported. Use of this
      technique for hip pain control is controversial. In our experience, percutaneous
      radiofrequency lesioning of the sensory branches of the nerves innervating the
      hip joint can be an option for patients with intractable hip joint pain.

PMID- 22385438
TI  - Cancellous impaction bone grafting of acetabular defects in complex primary and
      revision total hip arthroplasty.
AB  - The reconstruction of major acetabular bone defects during revision, conversion,
      and primary total hip arthroplasties (THAs) is challenging. We reviewed a
      consecutive series of 168 THAs (108 revisions, 8 conversions, and 52 primary
      THAs) performed by 1 surgeon (S.B.G.) between 1997 and 2008 using impaction bone
      grafting for acetabular reconstruction. Autograft, cancellous allograft croutons,
      and demineralized bone matrix were used to fill bone defects as needed. The
      acetabular bone deficiency was classified according to the American Academy of
      Orthopaedic Surgeons: type I, segmental deficiency with significant rim defect;
      type II, cavitary defects medially or posteriorly; type III, combined cavitary
      and segmental deficiency; type IV, pelvic discontinuity; and type V, arthrodesis.
      According to this method, 56 hips had type I, 31 hips had type II, 48 hips had
      type III, and 27 hips had type IV deficiencies. Of the 168 patients, 19
      subsequently died of causes unrelated to the THA, and 11 were lost to follow-up.
      All patients had at least 2 years of follow-up. Average Harris Hip Score improved
      from 45.5+/-17.9 preoperatively to 81.1+/-16.5 postoperatively (P<.05) for
      revision THAs, from 40.0+/-11.3 preoperatively to 85.0+/-12.8 postoperatively
      (P<.05) for conversion THAs, and from 42.3+/-14.9 preoperatively to 85.0+/-12.0
      postoperatively (P<.05) for primary THAs. All impaction grafted bone (allograft,
      autograft, or a combination) incorporated radiographically, thus restoring bone
      stock. Complications included 1 early infection, which was managed successfully
      with debridement and liner exchange, and 2 late infections that were managed
      successfully with staged revision. Two revisions required subsequent re-revision
      for late loosening. Two hip dislocations occurred, 1 of which required surgical
      treatment to place a constrained liner.

PMID- 22385439
TI  - 15-year comparison of cementless total hip arthroplasty with anatomical or high
      cup placement for Crowe I to III hip dysplasia.
AB  - This study compared radiological and clinical results of Mallory-Head (Biomet,
      Warsaw, Indiana) cementless total hip arthroplasty (THA) by anatomical (AP group)
      or high cup placement (HP group) for Crowe I to III developmental dysplasia of
      the hip. Of the 68 hips studied, 43 hips were available for 15.3-year follow-up.
      Ten cups were placed at anatomical center with bulk bone grafting, and 33 cups
      were at high hip center without bulk bone grafting. No acetabular or femoral
      components showed loosening in either group. One standard polyethylene liner in a
      highly placed cup was revised due to excessive wear after 11 years. The average
      rate of polyethylene wear was 0.128 mm/year in the AP group and 0.148 mm/year in
      the HP group (except for the revision case). The extent of grafted bone coverage
      was 34.6% in the AP group. Hip center height was 24.5 mm from the inter-teardrop
      line in the HP group. The center of the hip horizontal location in the AP group
      (24.5 mm) and HP group (26.4 mm) was significantly shorter than in normal hips
      (35.6 mm). Postoperative center-edge angle was 11 degrees  (except grafted bone)
      in the AP group and 25 degrees  in the HP group. Mean Harris Hip Score in the AP
      group improved from 38 points preoperatively to 82 points postoperatively and in
      the HP group improved from 40 points preoperatively to 88 points postoperatively.
      Survivorship was 100% in the AP group and 97% in the HP group. Our results
      indicate that moderate high cup placement without bulk bone grafting at a
      horizontal locus more medial than that of a normal hip is an alternative durable
      solution.

PMID- 22385440
TI  - Hemodynamically unstable pelvic fracture management by advanced trauma life
      support guidelines results in high mortality.
AB  - The purpose of this study was to examine the acute outcomes and mortality rates
      of an Advanced Trauma Life Support guideline approach for managing
      hemodynamically unstable pelvic ring injuries. We retrospectively reviewed the
      acute outcomes of 48 consecutive patients with hemodynamically unstable pelvic
      fractures. Patients underwent treatment via the advanced trauma life support
      protocol, with primary angiography based on trauma surgeon preference. Mean
      patient age was 51.2 years, with a mean injury severity score of 43.2+/-14.3.
      Mean systolic blood pressure was 74.8+/-16.1 mm Hg at presentation. Patients
      received an average of 7.0+/-6.6 units of red blood cells and 4.2+/-2.3 units of
      fresh frozen plasma in the first 6 hours. Fourteen patients underwent emergent
      angiography, and 12 patients were treated with embolization. Mean time to
      angiography was 3 hours and 55 minutes (range, 2-19 hours). Twenty patients died
      during hospitalization, with an overall mortality rate of 41.7%; 13 (27.1%) of
      them died within 24 hours. Advanced Trauma Life Support guidelines with
      angiography are not adequate for the management of hemodynamically unstable
      pelvic ring injuries and result in unacceptably high mortality rates compared
      with more specific approaches using transfusion protocols and interventions, such
      as pelvic packing.

PMID- 22385441
TI  - Rotating-hinge total knee for revision total knee arthroplasty.
AB  - Rotating-hinge knee implants are used for revision total knee arthroplasty in
      patients with severe ligament instability and bone loss. This study evaluated the
      outcomes of a series of rotating-hinge knees. Thirty-one NexGen Rotating Hinge
      Knees (Zimmer, Warsaw, Indiana) were implanted in 29 patients (2 bilateral), with
      an average age of 72.8 years. Indications for surgery were aseptic loosening
      (n=23), septic loosenings (n=4), tibiofemoral instability (n=3), and wear (n=1).
      The Hospital for Special Surgery Knee Score and the Knee Society Roentgenographic
      Evaluation System were used. Statistical and cumulative survival rate analyses
      were performed. Average follow-up was 60.3 months (range, 32-100 months). The
      Hospital for Special Surgery Knee Score results indicated statistically
      significant improvement; the total score increased from 65.5 preoperatively to
      88.4 postoperatively. Average range of motion increased from 90.9 degrees 
      preoperatively to 114.4 degrees  postoperatively. Radiographs showed no
      periprosthetic bone fractures or implant ruptures. Radiolucent lines were found
      in 20 of 26 patients and were progressive in 2 (both revised). Complications
      occurred in 10 patients. The rigidity of the hinge may be associated with a risk
      of aseptic loosening due to the increased stress transfer to the bone from the
      prosthesis through the locked hinge. Rotating-hinge knee implants provided
      acceptable mid-term outcomes for revision knee surgery with ligamentous
      instability. They are not at higher risk for early loosening unless short tibial
      stems are used. The high percentage of failures is more related to the complex
      surgery and to the status of the patients than to the hinged mechanism.

PMID- 22385442
TI  - Xenograft scaffold full-wrap reinforcement of Krackow achilles tendon repair.
AB  - Standard 4-strand repair of Achilles tendon tears is effective, but additional
      strength may be desirable in patients who are compromised or those with
      reruptures. Use of a xenograft scaffold has not been investigated biomechanically
      in Achilles tendon repair. This study compared stiffness, gap formation, and
      ultimate load to failure with Krackow repair vs Krackow repair augmented with
      xenograft scaffold in 6 matched pairs of fresh-frozen human lower extremities.
      The Achilles tendon was transected 4 cm above the calcaneal insertion. Specimens
      were randomized to receive standard Krackow repair or Krackow repair augmented
      with a porcine xenograft scaffold. The graft was wrapped around the repaired
      tendon, sutured to itself with 2-0 FiberWire (Arthrex, Naples, Florida), and
      attached to the tendon distally and proximally and then medially and laterally.
      Specimens were loaded for 200 cycles between 5 and 30 N. Load to 5-mm gapping and
      load to ultimate failure were measured. Xenograft scaffold augmentation of
      standard Krakow Achilles tendon repair was significantly stronger and stiffer
      than standard Krackow repair in a biomechanical model immediately after repair
      (39.0+/-8.8 vs 24.4+/-4.6 N/mm; P=.01). The augmented repair group had
      significantly higher load to ultimate failure than did the Krackow group (862.7+/
      174.0 vs 479.5+/-65.5 N; P<.01). Biological factors remain to be investigated,
      but this augmentation method could provide additional strength in patients who
      are compromised or those with reruptures.

PMID- 22385443
TI  - In vivo testing of knee stability after rotating-hinge total knee arthroplasty: a
      comparison of 2 knee systems.
AB  - Rotating-hinge knee prostheses are used for reconstruction in cases of severe
      articular compromise and major bone loss. Biomechanical studies revealed that
      rotating-hinge designs with long and cylindrical pegs are more stable than
      devices with short and more tapered ones. Twenty-five patients underwent clinical
      examination using ultrasound, radiographs, and 3 different rating systems to
      examine the in vivo stability and functional outcome of 2 rotating-hinge knee
      systems. Overall, the study revealed that a stable reconstruction could be
      achieved with both tested devices, with good functional outcome. The results for
      medial and lateral lift-off during flexion and extension in ultrasonography were
      comparable, whereas the measured distraction of the Limb Preservation System
      (LPS/M.B.T.; DePuy, Warsaw, Indiana) was lower compared with the S-ROM Noiles
      prostheses (DePuy). The implant, the new formed capsule, and the remaining soft
      tissues have to maintain joint stability. Soft tissue reconstruction, especially
      the medial gastrocnemius flap, and the newly formed periprosthetic scar seems to
      prevent distraction of several millimeters. In addition, determining the lift-off
      with ultrasonography showed that the shape of the peg does not influence
      implant's stability against lateral directed forces.

PMID- 22385444
TI  - Patelloplasty versus traditional total knee arthroplasty for osteoarthritis.
AB  - The purpose of this study was to compare the clinical effects of patelloplasty
      and traditional patellar management in total knee arthroplasty (TKA) for
      osteoarthritis. A total of 152 patients with osteoarthritis treated with TKA
      between January 2004 and December 2005 were retrospectively studied. The patients
      were randomly divided into 2 groups: the patelloplasty group (group A; n=76) and
      the traditional treatment group (group B; n=76). Knee Society Score (KSS), Feller
      patellar score, Lonner patellar score, patient satisfaction, joint range of
      motion (ROM), and incidence of postoperative anterior knee pain were compared
      between the groups. Mean follow-up was 55 months (range, 48-71 months) for 132
      patients, including 68 patients in group A and 64 in group B. Significant
      differences were found in KSS functional score, Feller patellar score, Lonner
      patellar score, and patient satisfaction, but no significant differences were
      found in ROM and total KSS score between the groups postoperatively. Group A
      obtained higher KSS scores and patient satisfaction than group B, with no
      significant difference in postoperative anterior knee pain. Postoperative
      radiographs revealed a significant difference in patellofemoral congruence
      between the groups. Patelloplasty relieves pain, enhances patient satisfaction,
      and improves function better than traditional patellar management in TKA with
      patellar nonresurfacing.

PMID- 22385445
TI  - Peripheral nerve injuries following gunshot fracture of the humerus.
AB  - Current best evidence supports observation for peripheral nerve palsies following
      a fracture of the humerus unless associated with an open fracture. However, the
      indications for nerve exploration with humerus gunshot fractures are unclear. All
      patients aged 18 to 89 years who were treated for a gunshot fracture of the
      humerus at an academic trauma center between 2004 and 2008 were retrospectively
      reviewed. Patient demographics, fracture characteristics, fracture healing, nerve
      injury, and intraoperative findings were examined. Twelve patients were
      identified, of which 6 had nerve palsies at presentation. Three patients had an
      isolated single nerve palsy, and all recovered spontaneously within 90 days with
      observation. The other 3 patients had a concomitant brachial artery laceration,
      and all required a secondary nerve procedure, including 1 primary nerve repair
      for a near complete transection and 2 re-explorations with neurolysis due to lack
      of spontaneous recovery by 90 days. Nerve palsies are common after gunshot
      fractures of the humerus, but nerve transections are uncommon. We observed 1
      nerve transection in 12 cases. However, in all 3 cases with a brachial artery
      injury, a nerve injury required surgical intervention. Subsequently, we recommend
      continued observation of isolated nerve palsies associated with gunshot fractures
      of the humerus. However, consider early nerve exploration of palsies when
      associated with a concomitant vascular injury.

PMID- 22385446
TI  - Outcomes of elderly patients with proximal femoral fractures according to
      positive criteria for surgical treatment.
AB  - Proximal femoral fractures in elderly patients are a serious problem in the aging
      society. Recently, surgical indications have changed due to advancements in
      medical technology. The purpose of this study was to investigate the outcome of
      elderly patients with displaced proximal hip fractures according to our positive
      criteria for surgical treatment. Exclusion criteria included (1) terminal-stage
      malignancy; (2) a combination of an inability to walk, a severe mental disorder,
      and caregiver refusal of surgery; and (3) nonapproval of the anesthesiologist for
      surgery. The study group comprised 666 elderly patients. They were categorized
      into surgically and nonsurgically treated groups, and their treatment outcomes
      were retrospectively analyzed. The majority of patients were treated surgically
      (97.0% vs 3.0%). One-year survival rate was higher among surgically treated
      patients (82.2%-91.8%) than non-surgically treated patients (55%). The major
      cause of death in nonsurgically treated patients was deterioration of
      comorbidities (66.7%), whereas this was the cause of death in 18.9% of surgically
      treated patients. One-year survival rates were worse in both groups with a lower
      American Society of Anesthesiologists grade. The 1-year survival rate of our
      patients suggests that our surgical criteria offer a reasonable outcome in
      surgically and nonsurgically treated patients. American Society of
      Anesthesiologists grade and preexisting comorbidities were strongly correlated
      with patient outcome.

PMID- 22385447
TI  - Treatment of complicated tibial plateau fractures with dual plating via a 2
      incision technique.
AB  - The operative treatment of complicated bicondylar fractures of the tibial plateau
      remains a challenge to most surgeons. This retrospective study was designed to
      evaluate the clinical and radiological outcomes of dual plating via a 2-incision
      technique for the repair of complicated bicondylar tibial plateau fractures. A
      series of consecutive patients with bicondylar tibial plateau fractures treated
      by open reduction and internal fixation with a double buttress plate or a
      combination of locking plate and buttress plate via a 2-incision technique
      between March 2004 and March 2008 were retrospectively analyzed. Radiological and
      clinical results and complications of the 2 different fixation methods were
      compared. Seventy-nine patients matching the criteria of this study were followed
      up for at least 24 months. All of the fractures healed, with 3 cases of deep
      infection, 7 cases of secondary loss of reduction, 3 cases of secondary loss of
      alignment, and 10 cases of knee instability. At 24-month follow-up, mean Hospital
      for Special Surgery scores were 77.8+/-9.4 and 79.0+/-7.9 in the double buttress
      plate group and combination group, respectively. No significant differences in
      clinical or radiographic outcomes were found between the 2 groups, except that
      the combination group needed less bone graft. Dual plating with 2 incisions
      provided good exposition for the reduction and fixation of complicated bicondylar
      tibial plateau fractures. Using a combination of locking plate and buttress plate
      reduced the amount of bone graft compared with the double buttress plate
      technique.

PMID- 22385448
TI  - Prospective outcomes of arthroscopic treatment of dorsal wrist ganglia.
AB  - The purpose of this study was to assess the results of arthroscopic resection of
      dorsal wrist ganglia. Between November 2002 and September 2007, all patients with
      dorsal wrist ganglia underwent arthroscopic resection in our institution. Average
      follow-up was 39.2 months (range, 24-71 months). Fifty-two patients (40 women and
      12 men; mean age, 29.8 years) were treated with our operative technique. Symptoms
      at presentation were unpleasant appearance in 15 patients (28.8 %), pain in 30
      (57.6%), and unpleasant appearance and pain in 7 (13.5%). The ganglion cyst site
      was in front of the midcarpal joint in 41 patients (78.8%), in front of the
      radiocarpal joint in 6 patients (11.5%), and in front of the radiocarpal and
      midcarpal joints in 5 patients (9.6%). Our surgical technique resulted in a
      significant improvement in flexion, extension, and grip strength (P<=.005). In
      patients with painful ganglia, treatment also had a significant effect. Nine
      (17.3%) recurrences were observed. Mean time off work was 14 days, but 19
      patients returned to work immediately. According to the results of this study, we
      recommend the use of arthroscopy as the primary treatment method for dorsal wrist
      ganglion excision.

PMID- 22385449
TI  - Comparison of phenol and argon beam coagulation as adjuvant therapies in the
      treatment of stage 2 and 3 benign-aggressive bone tumors.
AB  - Argon beam photocoagulation has gained popularity as an adjuvant therapy for the
      treatment of giant cell tumors of bone and other stage 2 or 3 benign-aggressive
      bone tumors. Although argon beam photocoagulation has been considered a safe and
      reasonable adjuvant treatment with acceptable recurrence rates, it has never been
      directly compared with the commonly described phenol as adjuvant. The purpose of
      this study was to determine whether argon beam photocoagulation is as effective
      as phenol in preventing recurrence without affecting functional outcome as an
      adjuvant to surgical curettage. We retrospectively reviewed 93 consecutive
      patients with a minimum 10-month follow-up between 1992 and 2007 who were treated
      with curettage and either phenol or argon beam photocoagulation. Functional
      outcomes and complications were recorded. Overall, 16 (17.2%) of 93 patients who
      were initially treated with 1 of the adjuvants had pathologically confirmed
      recurrences. No additional recurrences were noted after retreatment, leading to
      an overall recurrence rate of 17.1% with phenol and 14.8% with argon beam
      photocoagulation (P=.726). While avoiding the toxic effects of phenol, argon beam
      photocoagulation provides for statistically equivalent recurrence rates,
      functional outcomes, and complication rates in the treatment of benign-aggressive
      bone tumors.

PMID- 22385450
TI  - Chondrosarcomas revisited.
AB  - Chondrosarcomas are malignant bone tumors with pure hyaline cartilage
      differentiation; myxoid changes, calcification, or ossification may be present.
      Several subtypes of chondrosarcomas exist. Behavior patterns vary, ranging from
      slow-growing nonmetastasizing lesions to aggressive metastasizing sarcomas.
      Symptoms are usually mild, with duration ranging from several months to years,
      and usually consist of persistent, dull, aching pain or palpable masses.
      Radiographic findings include bone expansion with cortical thickening,
      radiolucent areas with variably distributed punctate or ring-like matrix
      calcifications, cortical erosion or destruction, endosteal scalloping, and scant
      or absent periosteal reaction; extension into the soft tissue may be present.
      Histological differential diagnosis from benign cartilaginous lesions can be
      achieved by increased cellularity, enlarged plump nuclei, binucleated cells,
      hyperchromatic nuclear pleomorphism, and permeation of cortical or medullary
      bone. Atypia is usually mild to moderate; necrosis and mitoses can be seen,
      particularly in high-grade lesions. Adequate surgery is the mainstay of
      treatment. High-grade and pelvic chondrosarcomas are best managed with wide
      resection. Because of the low metastatic potential and low local recurrence rate
      noted with intralesional surgery, low-grade chondrosarcomas can be treated with
      curettage (with or without treatment of the defect cavity) with a local adjuvant,
      such as phenol or cryotherapy. Adjuvant chemotherapy may be considered for
      mesenchymal and dedifferentiated chondrosarcomas. Radiation therapy can be
      considered after incomplete resection or if resection is not feasible or would
      cause unacceptable morbidity.

PMID- 22385451
TI  - Clinical and functional outcomes of tibial intercalary allografts after tumor
      resection.
AB  - Reconstruction after intercalary resection of the tibia is demanding due to
      subcutaneous location, poor vascularity of the tibia, and high infection rate.
      The purpose of this study was to evaluate the survivorship, complications, and
      functional outcome of intercalary tibial allograft reconstructions following
      tumor resections. Intercalary tibia segmental allografts were implanted in 26
      consecutive patients after segmental resections. Patients were followed for an
      average of 6 years. Allograft survival was determined with the Kaplan-Meier
      method. Patient function was evaluated with the Musculoskeletal Tumor Society
      (MSTS) scoring system. Survivorship was 84% (95% confidence interval [CI], 98%
      70%) at 5 years and 79% (95% CI, 63%-95%) at 10 years. Allografts were removed in
      5 patients due to 3 infections and 2 local recurrences. Two patients showed
      diaphyseal nonunion, and 3 patients underwent an incomplete fracture; no
      allografts were removed in these patients. Average MSTS functional score was 29
      points (range, 27-30 points). Despite the incidence of complications, this
      analysis showed an acceptable survivor-ship with excellent functional scores. The
      use of intercalary allograft has a place in the reconstruction of a segmental
      defect created by the resection of a tumor in the diaphyseal or metaphyseal
      portion of the tibia.

PMID- 22385452
TI  - Allograft arthrodesis of the knee for giant cell tumors.
AB  - Giant cell tumors of bone are aggressive benign tumors. Wide resection is
      reserved for a small subset of patients with biologically more aggressive,
      recurrent, and extensive tumors. For patients with giant cell tumors who are
      young or middle-aged adults with normal life expectancies and high levels of
      activity, arthrodesis is an option for reconstruction after resection. We
      retrospectively studied 40 patients (mean age, 33.1 years) with Campanacci grade
      III giant cell tumors around the knee (12 distal femoral and 28 proximal tibial)
      that were treated with wide resection and allograft arthrodesis using compression
      plating between January 1998 and January 2008. At an average follow-up of 4.3
      years (range, 2-10 years), no patient had local recurrence, malignant
      transformation, or pulmonary or distant metastases. The grafts united proximally
      and distally in 35 (87.5%) patients. Average limb-length shortening was 2 cm
      (range, 1.5-5 cm). No patient needed a lengthening procedure. Functional outcomes
      according to the Musculoskeletal Tumor Society measure were successful, with an
      average score of 26.3 points (range, 22-30 points). Wide resection with allograft
      arthrodesis of the knee is a treatment option in young, active patients with
      Campanacci grade III giant cell tumors around the knee. Wide resection and
      reconstruction with knee allograft arthrodesis for giant cell tumors can achieve
      excellent control of disease, high fusion rates, acceptable functional results,
      and low complication rates.

PMID- 22385453
TI  - Segmental anterior decompression and fusion for multilevel ossification of the
      posterior longitudinal ligament.
AB  - The purpose of this study was to evaluate the outcome of segmental anterior
      decompression and fusion for multilevel ossification of the posterior
      longitudinal ligament. Data were collected from 23 patients with multilevel
      ossification of the posterior longitudinal ligament. Average operative time and
      blood loss were 121 minutes and 201.6 mL, respectively. The Nurick score
      significantly decreased from 2.7+/-0.9 preoperatively to 1.8+/-0.9 at last follow
      up (P<.01). The preoperative Japanese Orthopaedic Association score was 8.2,
      which significantly increased to 13.8 points at last follow-up (P<.01), with an
      improvement rate of 64.5%. The operation also significantly increased cervical
      lordosis (P<.01) from 7.7 degrees  preoperatively to 13.3 degrees 
      postoperatively. The fusion rate was 95.7% at 6 months postoperatively, and 100%
      at 12 months postoperatively. The loss of cervical lordosis and height of fusion
      segments were 1.2 degrees  and 0.9 mm at last follow-up, respectively. No
      hardware complications occurred. Cerebrospinal fluid leakage occurred in 2
      patients, and hematoma occurred in 1 patient who needed an emergency operation.
      Segmental anterior decompression and fusion was generally effective and safe in
      the treatment of multilevel ossification of the posterior longitudinal ligament
      if indications were well controlled.

PMID- 22385454
TI  - Detection of Mycobacterium tuberculosis DNA in the sclerotic spinal wall.
AB  - Recent studies have shown that the major spinal lesion in spinal tuberculosis is
      predominantly sclerotic and accounts for >70% of the lesion. In this type of
      sclerosis, apart from spinal reactive hyperplasia and increased bone density, the
      most severe lesion is the formation of a hard outer osteoid shell (the sclerotic
      wall) around the cheese-like substances and granulated tissues. In the current
      study, polymerase chain reaction detection of Mycobacterium tuberculosis in the
      sclerotic wall was performed. Surgical specimens were obtained from 18 patients
      with spinal tuberculosis with peripheral sclerotic wall (as shown by computed
      tomography) and included the sclerotic wall, subnormal bone tissue outside the
      sclerotic wall, and iliac bone tissue (control). The IS986 gene in the samples
      was amplified by polymerase chain reaction followed by DNA sequencing. The
      obtained sequences were then compared with the published sequences in GenBank
      using DNATools version 5.1 software (International Centre for Genetic Engineering
      and Biotechnology, Trieste, Italy). The polymerase chain reaction results showed
      that 16 specimens from the sclerotic spinal wall, 3 from the subnormal bone, and
      0 from the controls were positive for M tuberculosis, indicating a statistically
      significant difference (P<.05). These results indicated that M tuberculosis was
      present in the spinal sclerotic wall. Combined with our previous studies, we
      conclude that the sclerotic wall should be considered a lesion in patients with
      spinal tuberculosis.

PMID- 22385455
TI  - Review of medicolegal cases for cauda equina syndrome: what factors lead to an
      adverse outcome for the provider?
AB  - Cauda equina syndrome is 1 of a few true surgical emergencies involving the
      lumbar spine. Although treatment within 48 hours has been found to correlate with
      improved outcomes, recovery of bowel and bladder control does not always occur,
      and loss of these functions can be distressing to patients. An understanding of
      factors affecting the legal outcome can aid the clinician in determining risk
      management for medicolegal cases of cauda equina syndrome. This study is a
      retrospective analysis of medicolegal cases involving cauda equina syndrome. The
      LexisNexis Academic legal search database was used to obtain medicolegal cases of
      cauda equina syndrome to determine risk factors for adverse decisions for the
      provider. Outcomes data on trial verdicts were collected, as were associated
      penalties. Case data were also compiled on age, sex, initial presentation site,
      initial diagnosis, whether a rectal examination was performed, time to
      consultation with a specialist, time to completion of advanced imaging study,
      time to surgery, and neurosurgical vs orthopedic consultation. Based on our study
      of court cases involving cauda equina syndrome, a positive association was found
      between time to surgery >48 hours and an adverse decision (P<.05). The actual
      degree of functional loss did not appear to affect the verdicts. Because 26.7% of
      the cases involved an initial presentation that included loss of bowel or bladder
      control, this study emphasizes the importance of cautioning all patients with
      spinal complaints of the potential risk for cauda equina syndrome.

PMID- 22385456
TI  - Orthopedic specialty hospitals: centers of excellence or greed machines?
AB  - Orthopedic specialty hospitals have recently been the subject of debate. They are
      patient-centered, physician-friendly health care alternatives that take advantage
      of the economic efficiencies of specialization. Medically, they provide a higher
      quality of care and increase patient and physician satisfaction. Economically,
      they are more efficient and profitable than general hospitals. They also
      positively affect society through the taxes they pay and the beneficial aspects
      of the competition they provide to general hospitals. Their ability to provide a
      disruptive innovation to the existing hospital industry will lead to lower costs
      and greater access to health care. However, critics say that physician ownership
      presents potential conflicts of interest and leads to overuse of medical care.
      Some general hospitals are suffering as a result of unfair specialty hospital
      practices, and a few drastic medical complications have occurred at specialty
      hospitals. Specialty hospitals have been scrutinized for increasing the
      inequality of health care and continue to be a target of government regulations.
      In this article, the pros and cons are examined, and the Emory Orthopaedics and
      Spine Hospital is analyzed as an example. Orthopedic specialty hospitals provide
      excellent care and are great assets to society. Competition between specialty and
      general hospitals has provided added value to patients and taxpayers. However,
      physicians must take more responsibility in their appropriate and ethical
      leadership. It is critical to recognize financial conflicts of interest, disclose
      ownership, and act ethically. Patient care cannot be compromised. With thoughtful
      and efficient leadership, specialty hospitals can be an integral part of
      improving health care in the long term.

PMID- 22385457
TI  - Rotational acetabular osteotomy for habitual hip dislocation with posterior
      acetabular wall deficiency in patients with Down syndrome.
AB  - Hip dislocation associated with Down syndrome is relatively rare. Hip dislocation
      can progress to severe subluxation or habitual dislocation if the initial therapy
      is improperly performed. However, definitive treatment guidelines for
      conservative and surgical therapy for hip dislocation in patients with Down
      syndrome have not been established. This article describes a case of a 12-year
      old girl with Down syndrome with nontraumatic habitual hip dislocation. Her hip
      joint was associated with acetabular dysplasia and hypoplasia of the posterior
      acetabular wall. Although conservative therapy was initially performed, no
      effects were observed. Rotational acetabular osteotomy and capsular plication
      were performed to reconstruct the posterior acetabular wall. No postoperative
      redislocation occurred, and the treatment effects were favorably sustained for 2
      years. In Down syndrome, few cases of developmental dysplasia and hypoplasia of
      the posterior acetabular wall have been reported. In previous reports, these
      morphological abnormalities were rarely taken into consideration when determining
      the treatment strategy, and to our knowledge, no other reports demonstrate
      therapy involving rotational acetabular osteotomy for hip dislocation complicated
      with Down syndrome. Whether the acetabulum had posterior wall deficiency was
      thought to be important for conservative and surgical therapies in hip
      dislocation in patients with Down syndrome. Rotational acetabular osteotomy could
      be an effective surgical procedure for reconstruction of the acetabulum by
      posterolateral rotation of the osteotomized acetabulum.

PMID- 22385458
TI  - Arthroscopic partial meniscectomy of a posteriorly flipped superior leaflet in a
      horizontal medial meniscus tear using a posterior transseptal portal.
AB  - This article describes a case of an arthroscopic partial meniscectomy of a
      posteriorly flipped superior leaflet in a horizontal medial meniscus tear using
      the posterior transseptal portal. An arthroscopic partial meniscectomy for bucket
      handle or flap tears in medial or lateral compartments using ordinary portals is
      a relatively common procedure in irreparable cases. However, the posterior
      compartment of the knee is not readily accessible through ordinary arthroscopic
      portals. Therefore, it has been considered a blind spot. Through the posterior
      transseptal portal, surgeons can achieve excellent arthroscopic visualization of
      the posterior compartment and easily perform arthroscopic procedures of the
      posterior compartment of the knee. A 48-year-old woman presented with a 1-year
      history of pain in the medial aspect of the right knee joint. Preoperative
      magnetic resonance imaging revealed a thinning of the medial meniscus posterior
      horn in coronal images and a sharp-edged triangle arising from the medial
      meniscus posterior horn between the medial femoral condyle and medial meniscus
      posterior horn on sagittal images (flipped-over sign). During the arthroscopic
      procedure, we found that the flipped leaflet was displaced posteriorly and was
      not mobile between the medial femoral condyle and medial meniscus posterior horn.
      Partial meniscectomy for a posteriorly displaced fragment can be performed
      successfully using the posterior transseptal portal. The posterior transseptal
      portal is useful for an arthroscopic partial meniscectomy of a posteriorly
      flipped leaflet in the posterior compartment of the knee.

PMID- 22385459
TI  - Ulnar fracture with late radial head dislocation: delayed Monteggia fracture.
AB  - Monteggia fractures are rare but commonly discussed lesions, with increasing
      complications due to late diagnosis. This article describes a case of a Monteggia
      fracture with delayed dislocation of the radial head. Previous radiographs of a 2
      year 8-month-old boy show complete fracture of the distal ulna, with no radial
      head dislocation. The radial head remained well positioned after 4 weeks. Seven
      years later, he sustained another arm injury. He was diagnosed with a hematoma
      but was later believed to have nursemaid's elbow. He presented to our institution
      5 weeks after the injury, and the radial head was found to be chronically
      dislocated, indicating a displacement occurring sometime during the past 7 years.
      After failing conservative treatment, the patient underwent surgical repair. The
      annular ligament was reconstructed using a harvested triceps fascia band, and an
      ulnar osteotomy was performed. A review of the literature found few reports of
      delayed Monteggia fractures, which accounted the delayed dislocations to ulnar
      angulation. However, our patient showed minimal ulnar angular deformity. We
      propose that the initial fracture disrupted the annular ligament and the radial
      head spontaneously relocated prior to being seen, which put the radial head at
      risk for later dislocation. We present an alternative hypothesis of dislocation
      after fracture healing and report the longest known period of delay between
      fracture and dislocation.

PMID- 22385460
TI  - Use of the F-Tool for the removal of a bent intramedullary femoral nail with a
      sagittal plane deformity.
AB  - Locked intramedullary nailing is the current standard of treatment for femoral
      shaft fractures and has low complication rates. Bent femoral intramedullary nails
      resulting from secondary trauma are rare and technically challenging. This
      article describes a case of a 36-year-old man who presented with a bent femoral
      intramedullary nail following a motorcross accident. The patient had a previous
      femoral shaft fracture treated with an intramedullary nail. Previous reports
      outlined methods to remove bent femoral nails through the fracture site and
      proximally; however, this article describes a novel technique combining the use
      of a Midas Rex MR7 high-speed burr (Medtronic, Minneapolis, Minnesota) and the F
      Tool (Synthes, West Chester, Pennsylvania) to facilitate nail extraction.The
      patient was placed in the lateral decubitus position. After limited exposure at
      the fracture site, the intramedullary nail was weakened at the apex of the
      deformity with a Midas Rex MR7 high-speed burr. We then used the F-Tool to
      straighten the nail to facilitate removal through the original proximal insertion
      site. The F-Tool allows forces to be concentrated at the apex of the deformity
      and minimizes soft tissue damage. Additional advantages of our technique include
      limited exposure and the ability to remove the nail in 1 piece.

PMID- 22385461
TI  - Clavicle nonunion in a 10-year-old boy.
AB  - Posttraumatic clavicle nonunion is rare, particularly in children. Four cases of
      clavicle fracture nonunion in patients aged 10 years and younger have been
      reported. A variety of techniques have been used to treat pediatric clavicle
      nonunions. A 10-year-old boy presented to our institution after a fall,
      sustaining a right closed midshaft clavicle fracture. No other injuries occurred,
      and neurovascular examination of the right upper extremity was normal. The
      fracture was initially treated with a sling for >4 months, and the fracture
      progressed to a hypertrophic nonunion. Serial radiographs failed to demonstrate
      progression to union. The patient continued to have pain with activity 4 months
      after his injury. Clavicle pseudarthrosis was considered; however, radiographs
      did not have the characteristic appearance of this condition. This fracture
      nonunion was treated with internal fixation and united with no complication. The
      patient was back to full activities of daily living 6 months postoperatively. He
      reported no tenderness at the fracture site or along the hardware. The treating
      surgeon (A.M.S.) prefers to remove hardware in young children, but the family
      declined removal. Pediatric posttraumatic nonunion of the clavicle is rare but
      can be safely treated with plate fixation, with excellent results.

PMID- 22385462
TI  - Avascular necrosis of the hamate treated with capitohamate and lunatohamate
      intercarpal fusion.
AB  - This article describes a case of a 58-year-old man with no significant underlying
      disease who had chronic pain due to osteonecrosis of the hamate. Following
      physical examination, imaging, and laboratory findings, he underwent surgical
      exploration via a limited dorsal approach. The hamate bone did not have a normal
      anatomical appearance or structure. It was marble-like in appearance, soft,
      friable, and lacking physiologic contour and bone strength. We removed the dorsal
      aspect of the hamate piecemeal. The articular surfaces of the adjacent carpal
      bones (capitate and lunate) were excised, and the lesion was packed with iliac
      autograft. Three months postoperatively, fusion of the remaining hamate and the
      adjacent capitate and lunate carpal bones was evident, and the patient reported
      mild wrist pain, moderate grip strength improvement, and mild improvement of
      wrist range of motion and stiffness. Currently, no standard treatment algorithm
      exists for patients with avascular necrosis of the hamate. However, delayed
      diagnosis of this clinical entity can be debilitating. A high index of clinical
      suspicion and an early course of treatment offers considerable benefits to
      patients with osteonecrosis of the hamate.

PMID- 22385463
TI  - Soft tissue tumor recurrence after intramedullary stabilization of impending
      pathologic fractures.
AB  - This article describes the cases of 3 patients who were treated for impending
      pathologic fractures with intramedullary stabilization who developed soft tissue
      tumor recurrence along the surgical tract site postoperatively, with confirmed
      histologic diagnoses consistent with each of their prior-known metastatic
      primaries. This sequela of treatment can lead to additional surgical procedures,
      longer recovery, and a delay in further systemic treatment, which negatively
      affects patient outcomes and survival. This can occur despite the use of adjuvant
      radiation therapy to the surgical site. Between June 2008 and July 2010, our
      institution surgically treated 71 pathologic (or impending) fractures, of which
      52 were femoral nails and 19 were humeral nails. Three of these patients
      sustained soft tumor tissue recurrence along the surgical tract. Due to the
      unfavorable long-term prognoses for patients with metastatic disease, these
      surgeries are palliative and not curative in nature. The purpose of this article
      is to draw attention to this sequala and heighten awareness for physicians who
      treat inpending or pathologic fractures. It is difficult to make strong
      recommendations based on a series of 3 patients, but some general principles can
      be used. We recommend copious intraoperative irrigation of the wound sites and
      consideration for routine surveillance with physical examination and prompt
      imaging and biopsy if any suspicion for local soft tissue recurrence arises. Our
      approach includes fine-needle aspiration of suspicious lesions followed by
      resection. The plastic surgery team is consulted pre- or intraoperatively if the
      resection defect cannot be closed primarily. The patient is also referred back to
      a medical oncologist for consideration of systemic chemotherapy because soft
      tissue tumor recurrence is a sign of progressive disease.

PMID- 22385464
TI  - Giant cell tumor expanded into the thoracic cavity with spinal involvement.
AB  - This article describes a case of a giant cell tumor that expanded into the
      thoracic cavity and through the spinal canal into the vertebrae. A 36-year-old
      man presented with a 6-month history of back pain and dyspnea. Plain chest
      radiographs showed a huge mass accompanied by right pleural effusion. The mass
      involved the 12th thoracic spine, and the spinal cord was severely compressed.
      The tumor was resected with a 2-stage procedure. As a first stage to separate the
      tumor from the anterior vital structures under direct vision, thoracic surgeons
      performed a right thoracotomy with chest wall reconstruction from the 8th to 11th
      ribs. The right lung and inferior vena cava were gently retracted, and the tumor
      was carefully detached from these structures. We were not able to separate the
      tumor from the right diaphragm due to severe invasion; therefore, we performed
      partial resection of the right diaphragm with the tumor. After excision of the
      anterior part of the tumor, the thoracic wall was reconstructed with the right
      eighth rib and Marlex mesh. When the patient's general condition improved 2 weeks
      later, spondylectomy by posterior approach was performed. We achieved excision of
      a giant cell tumor that had expanded into the thoracic cavity and through the
      spinal canal into the vertebrae. The patient had achieved full rehabilitation
      with no neurological or respiratory abnormalities at 7 years postoperatively.

PMID- 22385465
TI  - Brace treatment resulting in overcorrection of adolescent idiopathic scoliosis.
AB  - Brace treatment for idiopathic scoliosis in skeletally immature children is the
      only effective nonoperative modality for the control of curve progression. The
      Charleston bending brace is a custom-molded spinal orthosis that holds the
      patient in a completely corrected or overcorrected position while worn at night.
      A 9-year-old girl presented with 10 degrees  right upper thoracic and 7 degrees 
      left lower thoracic curves and was Risser sign 0. Nighttime treatment with a
      Charleston bending brace was initiated when the left lower thoracic curve
      progressed to 19 degrees . After 27 months of nighttime brace wear, the lower
      thoracic curve was 21 degrees  to the right. Further investigation, including
      magnetic resonance imaging of the spine, failed to diagnose an identifiable
      explanation for this atypical occurrence. Conservative treatment may improve
      radiographic and cosmetic appearance. Overcorrection of the curve, although not
      likely, is possible when part-time or nighttime bracing is implemented as a means
      of conservative management.

PMID- 22385466
TI  - Adolescent femoroacetabular impingement from malunion of the anteroinferior iliac
      spine apophysis treated with arthroscopic spinoplasty.
AB  - This article describes a case of an acute anterior inferior iliac spine
      apophyseal avulsion fracture in an adolescent athlete progressing to secondary
      symptomatic femoroacetabular impingement from an inferiorly displaced malunion
      and its arthroscopic management. A 13-year-old boy with an acute minimally
      displaced avulsion fracture of the anterior inferior iliac spine apophysis had
      initial symptomatic improvement with conservative treatment and a 3-month symptom
      free period but then developed flexion-induced deep anterior groin pain and
      mechanical symptoms. Radiographs confirmed an inferiorly displaced malunion of
      the ipsilateral anterior inferior iliac spine apophysis in addition to acetabular
      retroversion and cam deformity. Surgical treatment, including arthroscopic
      spinoplasty, was performed. Despite some nonrestrictive heterotopic ossification,
      the patient had a successful clinical outcome at 18 months, with return to
      football, and a nonarthritic hip score of 98. Although anterior inferior iliac
      spine avulsion fractures have historically been considered relatively self
      limiting injuries, their malunion may be a previously missed cause of unrelenting
      or bimodal pain from secondary femoroacetabular impingement with possible
      degenerative consequences in young athletic patients. Anterior inferior iliac
      spine avulsion fractures may merit a lower degree of tolerance for displacement
      in the acute setting and a higher degree of clinical and radiographic scrutiny
      with surgical intervention, possibly in the form of arthroscopic spinoplasty in
      the more chronic one.

PMID- 22385467
TI  - The effect of growth hormone on sleep-related cardio-respiratory control in
      Prader-Willi syndrome.
AB  - AIM: To evaluate the effects of growth hormone (GH) treatment on control of
      breathing, heart rate and blood pressure during sleep in Prader-Willi Syndrome
      (PWS). STUDY DESIGN: In a prospective clinical case series study, sixteen
      consecutive PWS patients (median age 16 months at enrolment) were followed-up 6
      months (2-32 months) after commencing GH treatment. We compared heart rate (HR),
      Pulse Transit Time (PTT; an index of blood pressure, BP) and ventilatory
      responses to standard chemostimuli (4% CO(2) and 100% O(2)) during quiet sleep
      prior to and after commencing GH treatment. RESULTS: Growth hormone treatment
      increased arterial oxygenation during sleep but did not significantly improve
      breathing stability (apnoea-hypopnoea index remained unchanged). GH treatment did
      not alter ventilatory, HR and PTT chemoreceptor-mediated responsiveness (p = 0.23
      0.97) but did significantly improve the coupling between and HR and PTT,
      indicating that HR and BP rose (or fell) in parallel after but not before GH
      therapy (p = 0.01). CONCLUSION: Growth hormone treatment improves arterial
      oxygenation and cardiovascular function during sleep; these changes are not owing
      to improved (stronger) chemoreflex-mediated autonomic drive.

PMID- 22385468
TI  - Development of a portfolio of learning for postgraduate family medicine training
      in South Africa: a Delphi study.
AB  - BACKGROUND: Within the 52 health districts in South Africa, the family physician
      is seen as the clinical leader within a multi-professional district health team.
      Family physicians must be competent to meet 90% of the health needs of the
      communities in their districts. The eight university departments of Family
      Medicine have identified five unit standards, broken down into 85 training
      outcomes, for postgraduate training. The family medicine registrar must prove at
      the end of training that all the required training outcomes have been attained.
      District health managers must be assured that the family physician is competent
      to deliver the expected service. The Colleges of Medicine of South Africa (CMSA)
      require a portfolio to be submitted as part of the uniform assessment of all
      registrars applying to write the national fellowship examinations. This study
      aimed to achieve a consensus on the contents and principles of the first national
      portfolio for use in family medicine training in South Africa. METHODS: A
      workshop held at the WONCA Africa Regional Conference in 2009 explored the
      purpose and broad contents of the portfolio. The 85 training outcomes, ideas from
      the WONCA workshop, the literature, and existing portfolios in the various
      universities were used to develop a questionnaire that was tested for content
      validity by a panel of 31 experts in family medicine in South Africa, via the
      Delphi technique in four rounds. Eighty five content items (national learning
      outcomes) and 27 principles were tested. Consensus was defined as 70% agreement.
      For those items that the panel thought should be included, they were also asked
      how to provide evidence for the specific item in the portfolio, and how to assess
      that evidence. RESULTS: Consensus was reached on 61 of the 85 national learning
      outcomes. The panel recommended that 50 be assessed by the portfolio and 11
      should not be. No consensus could be reached on the remaining 24 outcomes and
      these were also omitted from the portfolio. The panel recommended that various
      types of evidence be included in the portfolio. The panel supported 26 of the 27
      principles, but could not reach consensus on whether the portfolio should reflect
      on the relationship between the supervisor and registrar. CONCLUSION: A portfolio
      was developed and distributed to the eight departments of Family Medicine in
      South Africa, and the CMSA, to be further tested in implementation.

PMID- 22385469
TI  - An abietane diterpenoid is a potent activator of systemic acquired resistance.
AB  - Abietane diterpenoids are major constituents of conifer resins that have
      important industrial and medicinal applications. However, their function in
      plants is poorly understood. Here we show that dehydroabietinal (DA), an abietane
      diterpenoid, is an activator of systemic acquired resistance (SAR), which is an
      inducible defense mechanism that is activated in the distal, non-colonized,
      organs of a plant that has experienced a local foliar infection. DA was purified
      as a SAR-activating factor from vascular sap of Arabidopsis thaliana leaves
      treated with a SAR-inducing microbe. Locally applied DA is translocated through
      the plant and systemically induces the accumulation of salicylic acid (SA), an
      important activator of defense, thus leading to enhanced resistance against
      subsequent infections. The NPR1 (NON-EXPRESSOR OF PR GENES1), FMO1 (FLAVIN
      DEPENDENT MONOOXYGENASE1) and DIR1 (DEFECTIVE IN INDUCED RESISTANCE1) genes,
      which are critical for biologically induced SAR, are also required for the DA
      induced SAR, which is further enhanced by azelaic acid, a defense priming
      molecule. In response to the biological induction of SAR, DA in vascular sap is
      redistributed into a SAR-inducing 'signaling DA' pool that is associated with a
      trypsin-sensitive high molecular weight fraction, a finding that suggests that DA
      orchestrated SAR involves a vascular sap protein(s).

PMID- 22385470
TI  - Red blood cell transfusion during septic shock in the ICU.
AB  - BACKGROUND: Transfusion of red blood cells (RBCs) remains controversial in
      patients with septic shock, but current practice is unknown. Our aim was to
      evaluate RBC transfusion practice in septic shock in the intensive care unit
      (ICU), and patient characteristics and outcome associated with RBC transfusion.
      METHODS: Prospective cohort study of all adult patients with septic shock (n =
      164) in six general ICUs during a 3-month period. Characteristics, other
      treatments, monitoring and outcome were compared in RBC-transfused and -non
      transfused patients. RESULTS: Ninety-nine patients (95% confidence interval 87
      111) received a median 900 ml (interquartile range 490-1405) of RBC during septic
      shock in ICU. Among transfused patients, there were more females [49/99 (49%) vs.
      22/65 (34%), P = 0.048] and surgical patients [39/99 (39%) vs. 14/65 (22%), P =
      0.02] than among patients not transfused. Also, admission simplified acute
      physiology score II was higher and minimal haemoglobin levels (days 1-3) were
      lower in transfused patients compared with those not transfused. In contrast,
      age, markers of shock and severity organ failure assessment score on day 1 and 90
      day mortality did not differ between RBC-transfused and -non-transfused patients.
      CONCLUSIONS: Most patients with septic shock received RBCs during shock, and
      these patients had higher disease severity and lower haemoglobin levels than
      those not transfused. In spite of this, mortality did not differ between groups
      neither in the unadjusted or adjusted analyses. However, neither the design nor
      the sample size allows us to make inferences about treatment effects, which
      underlines the need for large randomised, clinical trials on transfusion in
      septic shock.

PMID- 22385471
TI  - Review article: the iron overload syndromes.
AB  - BACKGROUND: Iron overload syndromes encompass a wide range of hereditary and
      acquired conditions. Major developments in the field of genetics and the
      discovery of hepcidin as a central regulator of iron homeostasis have greatly
      increased our understanding of the pathophysiology of iron overload syndromes.
      AIM: To review advances in iron regulation and iron overload syndrome with
      special emphasis on hereditary haemochromatosis, the prototype iron overload
      syndrome. METHODS: A PubMed search using words such as 'iron overload',
      'hemochromatosis', 'HFE', 'Non-HFE', 'secondary iron overload' was undertaken.
      RESULTS: Iron overload is associated with significant morbidity and mortality.
      Sensitive diagnostic tests and effective therapy are widely available and can
      prevent complications associated with iron accumulation in end- organs.
      Therapeutic phlebotomy remains the cornerstone of therapy for removal of excess
      body iron, but novel therapeutic agents including oral iron chelators have been
      developed for iron overload associated with anaemia. CONCLUSIONS: Iron overload
      disorders are common. Inexpensive screening tests as well as confirmatory
      diagnostic tests are widely available. Increased awareness of the causes and
      importance of early diagnosis and knowledge of the appropriate use of genetic
      testing are encouraged. The availability of novel treatments should increase
      therapeutic options for patients with iron overload disorders.

PMID- 22385473
TI  - Enhanced asymmetric induction for the copolymerization of CO2 and cyclohexene
      oxide with unsymmetric enantiopure salenCo(III) complexes: synthesis of
      crystalline CO2-based polycarbonate.
AB  - Enantiopure metal-complex catalyzed asymmetric alternating copolymerization of
      CO(2) and meso-epoxides is a powerful synthetic strategy for preparing optically
      active polycarbonates with main-chain chirality. The previous studies regarding
      chiral zinc catalysts provided amorphous polycarbonates with moderate
      enantioselectivity, and thus, developing highly stereoregular catalysts for this
      enantioselective polymerization is highly desirable. Herein, we report the
      synthesis of highly isotactic poly(cyclohexene carbonate)s from meso-cyclohexene
      oxide using dissymmetrical enantiopure salenCo(III) complexes in conjunction with
      bis(triphenylphosphine)iminium chloride (PPNCl) as catalyst. The presence of a
      chiral induction agent such as (S)-propylene oxide or (S)-2-methyltetrahydrofuran
      significantly improved the enantioselectivity regarding (S,S)-salenCo(III)
      catalyst systems. Up to 98:2 of RR:SS was observed in the resultant
      polycarbonates obtained from the catalyst system based on (S,S)-salenCo(III)
      complex 4d bearing an adamantyl group on the phenolate ortho position, in the
      presence of (S)-2-methyltetrahydrofuran. Primary ONIOM (DFT:UFF) calculations,
      which were performed to investigate the effect of the competitive coordination of
      (S)-induction agent versus cyclohexene oxide to Co(III) center on
      enantioselectivity, suggest that the (S)-C-O bond in cyclohexene oxide is more
      favorable for cleavage, due to the interaction between oxygen atom of (S)
      induction agent and (S)-C-H of the coordinated cyclohexene oxide. The highly
      isotactic poly(cyclohexene carbonate) is a typical semicrystalline polymer,
      possessing a melting point of 216  degrees C and a decomposition temperature of
      310  degrees C.

PMID- 22385472
TI  - Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on
      enhanced postprandial gastric accommodation and emptying: randomized controlled
      study evaluation by real-time ultrasonography.
AB  - BACKGROUND: Improvement in subjective symptoms has been reported in functional
      dyspepsia (FD) patients administered with acotiamide. Improvement was confirmed
      in meal-related symptoms, such as postprandial fullness, upper abdominal
      bloating, and early satiety. We examined the mechanism underlying the effects of
      acotiamide on gastric accommodation reflex (GAR) and gastroduodenal motility in
      FD patients. METHODS: Thirty-four FD patients (mean age, 40.4 years) were
      examined ultrasonographically before and after 14-18 days of acotiamide (100 mg
      t.i.d.) or placebo administration. To assess GAR, expansion rate in cross
      sectional area of the proximal stomach was measured after every 100-mL ingestion,
      using a straw, of up to 400 mL of a liquid meal (consomme soup, 13.1 kcal; 400
      mL) in a supine position. Next, we measured gastric emptying rate (GER), motility
      index (MI, antral contractions), and reflux index (RI, duodenogastric reflux) to
      assess gastroduodenal motility. Patients also completed a survey based on the
      seven-point Likert scale both before and after drug administration. KEY RESULTS:
      Of the 37 cases, 19 and 18 were administered with acotiamide and placebo A
      respectively, significant difference was observed in GAR between the acotiamide
      and placebo groups (21.7%vs 4.4%) after 400 mL ingestion. GER significantly
      accelerated after treatment in the acotiamide group (P = 0.012), no significant
      differences were observed in MI and RI between the two groups. Improvement rates
      were 35.3 and 11.8% for the acotiamide and placebo groups. CONCLUSIONS &
      INFERENCES: Acotiamide significantly enhances GAR and GER in FD patients.
      Acotiamide may have therapeutic potential for FD patients.

PMID- 22385474
TI  - Functional investigation of a schizophrenia GWAS signal at the CDC42 gene.
AB  - OBJECTIVES: SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was
      associated with schizophrenia in a recent genome-wide association study (GWAS).
      Reduced expression of CDC42 in schizophrenia has previously been reported. Our
      objective was to test whether the associated SNP affected CDC42 expression.
      METHODS: Two available SNP * gene expression datasets were accessed to test the
      effect of rs2473277 on CDC42 expression: (i) the mRNA by SNP Browser, which
      presents results of a genome-wide linkage study of gene expression, and (ii) the
      Genevar HapMap expression dataset. rs2473277 is in strong linkage disequilibrium
      (LD) with the SNP rs2473307 (r(2) =0.96), which is predicted to affect
      transcription factor binding. rs2473307 was directly tested for allelic effects
      on gene expression using a gene reporter assay in a human neuronal cell line.
      RESULTS: In both datasets, the schizophrenia risk allele at rs2473277 was
      associated with a reduction in CDC42 mRNA levels. In the reporter gene assay the
      risk allele at rs2473307 similarly reduced gene expression. CONCLUSIONS: We found
      evidence that rs2473307, in strong LD with the schizophrenia associated SNP
      rs2473277, is a functional variant at CDC42 that may increase risk for
      schizophrenia by reducing expression of CDC42.

PMID- 22385475
TI  - Structural analysis, enzymatic characterization, and catalytic mechanisms of beta
      galactosidase from Bacillus circulans sp. alkalophilus.
AB  - Crystal structures of native and alpha-D-galactose-bound Bacillus circulans sp.
      alkalophilus beta-galactosidase (Bca-beta-gal) were determined at 2.40 and 2.25 A
      resolutions, respectively. Bca-beta-gal is a member of family 42 of glycoside
      hydrolases, and forms a 460 kDa hexameric structure in crystal. The protein
      consists of three domains, of which the catalytic domain has an (alpha/beta)(8)
      barrel structure with a cluster of sulfur-rich residues inside the beta-barrel.
      The shape of the active site is clearly more open compared to the only homologous
      structure available in the Protein Data Bank. This is due to the number of large
      differences in the loops that connect the C-terminal ends of the beta-strands to
      the N-terminal ends of the alpha-helices within the (alpha/beta)(8) barrel. The
      complex structure shows that galactose binds to the active site as an alpha
      anomer and induces clear conformational changes in the active site. The
      implications of alpha-D-galactose binding with respect to the catalytic mechanism
      are discussed. In addition, we suggest that beta-galactosidases mainly utilize a
      reverse hydrolysis mechanism for synthesis of galacto-oligosaccharides.

PMID- 22385477
TI  - Effect of medicinal and aromatic plants on rumen fermentation, protozoa
      population and methanogenesis in vitro.
AB  - The potential of tannins from 21 medicinal and aromatic plant leaves as
      antimethanogenic additives in ruminant feeds was investigated. The effect of
      tannin from these leaves on rumen fermentation parameters, protozoa population
      and methanogenesis was studied by incubating the samples [200 mg dry matter (DM)]
      without and with polyethylene glycol (PEG)-6000 (400 mg DM) as a tannin binder
      during 24-h incubation in the in vitro Hohenheim gas method. Based on the methane
      percentage estimated in the total gas produced, methane production in millilitre
      was calculated [methane volume (ml) = methane % * total gas produced (ml) in 24
      h]. In the samples, crude protein and neutral detergent fibre (g/kg DM) ranged
      from 113 to 172 and from 352 to 444 respectively. The total phenol (TP; g/kg DM)
      content was highest in Terminalia chebula (274) followed by Hemigraphis colorata
      (71) and Sapindus laurifolia (51) respectively. In the remaining samples, it was
      <43 g/kg DM. Activity of tannins, as represented by the increase in gas volume on
      addition of PEG, ranged from 0 to 133%, with the highest being recorded in T.
      chebula. The per cent increase in methane on PEG addition was 0 for Ammi majus,
      Aristolochia indica, Cascabela thevetia, Ipomea nil and Lantana camara,
      illustrating that tannins present in these samples had no effect on methane
      concentration. The PEG addition increased the total protozoa count by >50% in A.
      indica and C. thevetica. One of the important findings of our study was that of
      the 21 samples screened, Entodinia population increased in 12 with PEG as
      compared to 7 where Holotricha increased, indicating higher susceptibility of
      Entodinia to tannin. There was no increase in the protozoa population with PEG
      when incubating Cardiospermum halicacabum, Clerodendrum inerme, Dioscorea
      floribunda, Nerium oleander and Selastras paniculatus, which strongly suggested
      that methane suppression recorded in these samples was not because of a
      defaunating effect of their tannins per se. The fermentation pattern reflected
      increased total volatile fatty acid (TVFA) concentration from 0 to 28.3% with PEG
      addition among the leaves. Our results confirmed further observations that
      methanogenesis in vitro is not essentially related to density of protozoa
      population. Secondly, medicinal and aromatic plants such as C. inerme, Gymnema
      sylvestre and Sapindus laurifolia containing tannins appear to have a potential
      to suppress in vitro methanogenesis.

PMID- 22385476
TI  - Structure-activity relationships in human Toll-like receptor 2-specific monoacyl
      lipopeptides.
AB  - Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)
      (2RS)-propyl]-R-cysteinyl-S-serine (PAM(2)CS) compounds are potential vaccine
      adjuvants. We had previously determined that at least one acyl group of optimal
      length (C(16)) and an appropriately orientated ester carbonyl group is essential
      for TLR2-agonistic activity. We now show that these structurally simpler
      analogues display agonistic activities with human, but not murine, TLR2. SAR
      studies on the monoacyl derivatives show that the optimal acyl chain length is
      C(16), and aryl substituents are not tolerated. A variety of alkyl and acyl
      substituents on the cysteine amine were examined. All N-alkyl derivatives were
      inactive. In contradistinction, short-chain N-acyl analogues were found to be
      highly active, with a clear dependence on the chain length. A cysteine N-acetyl
      analogue was found to be the most potent (EC(50): 1 nM), followed by the N
      butyryl analogue. The N-acetyl analogue is human TLR2-specific, with its potency
      comparable to that of PAM(2)CS.

PMID- 22385478
TI  - Testicular torsion: a 15-year single-centre clinical and histological analysis.
AB  - AIM: This study reviewed the demographic, epidemiological and clinical factors of
      boys seen at a single centre who underwent surgical exploration for testicular
      torsion. METHODS: Retrospective single-centre review of boys with testicular
      torsion between 1996 and 2011 was made. RESULTS: Testicular torsion (right n =
      43, left n = 60, bilateral n = 1) was identified in 104 boys between 0 and 18
      years. Ten newborns presented with 11 intrauterine torsions. Nine torsions
      presented in undescended inguinal testes (one intrauterine). In 94 boys with
      descended testes, presentation included pain (76%), scrotal swelling (65%) and
      abdominal symptoms (22%). Ultrasonography was performed in 85 patients with false
      negative results in 4 (4.7%). Orchiectomy was performed during initial
      exploration in 41, with significantly higher rates of orchiectomies in patients
      with late (>6 h) versus patients with early referrals (<6 h) (56% vs. 9.1%).
      Histological evaluation was carried out in 68 testes, with 43 resected testes
      demonstrating haemorrhagic necrosis. In 25 biopsied testes, histology revealed
      acute parenchymal bleeding (n = 14), onset of parenchymal infarction (n = 8),
      orchitis (n = 1) and normal tissue (n = 2). Eighty-two patients were followed up
      with pathological findings in four patients: testicular atrophies requiring
      orchiectomy (n = 2), testicular autolysis (n = 1) and small testicular vein
      thrombosis (n = 1). CONCLUSION: Chances of testicular salvage after torsion are
      higher if patients present early. The majority of patients presenting late (>6 h)
      require orchiectomy owing to testicular necrosis.

PMID- 22385479
TI  - Partial ligation of the transposed parotid duct at the level of the parotid gland
      for excessive salivary secretions.
AB  - OBJECTIVE: To determine the outcome and effect of a partial ligation of the
      transposed parotid duct at the level of the parotid gland in four dogs with
      excessive salivation and ocular irritation. METHODS: Four dogs were previously
      diagnosed with absolute keratoconjunctivitis sicca. After a parotid duct
      transposition (PDT) surgery, these dogs experienced excessive saliva production
      and abundant salivary precipitates, which resulted in epiphora, moist dermatitis,
      blepharospasm, and keratitis. In an effort to decrease saliva production, a
      partial ligation of the transposed duct at the level of the parotid gland was
      performed. Two or three accessory branches to the primary parotid duct were
      ligated at the level of the salivary gland. RESULTS: The four cases were three
      Yorkshire terriers and a Chihuahua. The average age of the four patients was 2.5
      years. Partial ligation of accessory branches of the parotid duct at the level of
      the parotid gland after a PDT in this study demonstrated improved ocular comfort,
      decreased salivary precipitates, and adequate Schirmer tear test results without
      marked epiphora in three of the four animals. The male Yorkshire had epiphora
      after the initial partial ligations of two accessory branches were placed at the
      level of the parotid gland. To correct the excessive salivary flow, two
      additional ligatures were placed at a later date, which resolved the epiphora.
      CONCLUSION: Partial ligation of the parotid duct at the level of the parotid
      gland proved to be an effective technique in moderating the salivation in these
      four patients with excessive salivary secretions after PDT.

PMID- 22385480
TI  - Microwave- and nitronium ion-enabled rapid and direct production of highly
      conductive low-oxygen graphene.
AB  - Currently the preferred method for large-scale production of solution-processable
      graphene is via a nonconductive graphene oxide (GO) pathway, which uncontrollably
      cuts sheets into small pieces and/or introduces nanometer-sized holes in the
      basal plane. These structural changes significantly decrease some of graphene's
      remarkable electrical and mechanical properties. Here, we report an unprecedented
      fast and scalable approach to avoid these problems and directly produce large,
      highly conductive graphene sheets. This approach intentionally excludes KMnO(4)
      from Hummers' methods and exploits aromatic oxidation by nitronium ions combined
      with the unique properties of microwave heating. This combination promotes rapid
      and simultaneous oxidation of multiple non-neighboring carbon atoms across an
      entire graphene sheet, thereby producing only a minimum concentration of oxygen
      moieties sufficient to enable the separation of graphene sheets. Thus, separated
      graphene sheets, which are referred to as microwave-enabled low-oxygen graphene,
      are thermally stable and highly conductive without requiring further reduction.
      Even in the absence of polymeric or surfactant stabilizers, concentrated
      dispersions of graphene with clean and well-separated graphene sheets can be
      obtained in both aqueous and organic solvents. This rapid and scalable approach
      produces high-quality graphene sheets of low oxygen content, enabling a broad
      spectrum of applications via low-cost solution processing.

PMID- 22385481
TI  - Surgeon and pathologist: an indissoluble marriage.

PMID- 22385482
TI  - Understanding substrate selectivity of human UDP-glucuronosyltransferases through
      QSAR modeling and analysis of homologous enzymes.
AB  - The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation
      reaction which is a major metabolic and detoxification pathway in humans.
      Understanding the mechanisms for substrate recognition by UGT assumes great
      importance in an attempt to predict its contribution to xenobiotic/drug
      disposition in vivo. Spurred on by this interest, 2D/3D-quantitative structure
      activity relationships and pharmacophore models have been established in the
      absence of a complete mammalian UGT crystal structure. This review discusses the
      recent progress in modeling human UGT substrates including those with multiple
      sites of glucuronidation. A better understanding of UGT active site contributing
      to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e.
      plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is
      also highlighted, as these enzymes share a common catalytic mechanism and/or
      overlapping substrate selectivity.

PMID- 22385483
TI  - Is corneal thickness an independent risk factor for glaucoma?

PMID- 22385484
TI  - Cataract surgery outcomes for right vs. left eyes.

PMID- 22385485
TI  - Macular hole surgery.

PMID- 22385486
TI  - Intravitreal triamcinolone in Coats' disease.

PMID- 22385487
TI  - Strabismus surgery hemostasis.

PMID- 22385488
TI  - Optic disc measurements.

PMID- 22385491
TI  - Disc drusen.

PMID- 22385492
TI  - Povidone-iodine and ophthalmia neonatorum.

PMID- 22385494
TI  - Trends in Canadian ophthalmology research.

PMID- 22385495
TI  - Accommodative esotropia.

PMID- 22385496
TI  - Resident OKAP performance.

PMID- 22385498
TI  - Synthesis and evaluation of a set of para-substituted 4-phenylpiperidines and 4
      phenylpiperazines as monoamine oxidase (MAO) inhibitors.
AB  - A series of para-substituted 4-phenylpiperidines/piperazines have been
      synthesized and their affinity to recombinant rat cerebral cortex monoamine
      oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole
      moment increased the affinity to MAO A, whereas groups with high dipole moment
      yielded compounds with no or weak affinity. In contrast, the properties affecting
      MAO B affinity were the polarity and bulk of the para-substituent, with large
      hydrophobic substituents producing compounds with high MAO B affinity. In
      addition, these compounds were tested in freely moving rats and the effect on the
      post-mortem neurochemistry was measured. A linear correlation was demonstrated
      between the affinity for MAO A, but not MAO B, and the levels of 3,4
      dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum.

PMID- 22385499
TI  - Active training and driving-specific feedback improve older drivers' visual
      search prior to lane changes.
AB  - BACKGROUND: Driving retraining classes may offer an opportunity to attenuate some
      effects of aging that may alter driving skills. Unfortunately, there is evidence
      that classroom programs (driving refresher courses) do not improve the driving
      performance of older drivers. The aim of the current study was to evaluate if
      simulator training sessions with video-based feedback can modify visual search
      behaviors of older drivers while changing lanes in urban driving. METHODS: In
      order to evaluate the effectiveness of the video-based feedback training, 10
      older drivers who received a driving refresher course and feedback about their
      driving performance were tested with an on-road standardized evaluation before
      and after participating to a simulator training program (Feedback group). Their
      results were compared to a Control group (12 older drivers) who received the same
      refresher course and in-simulator active practice as the Feedback group without
      receiving driving-specific feedback. RESULTS: After attending the training
      program, the Control group showed no increase in the frequency of the visual
      inspection of three regions of interests (rear view and left side mirrors, and
      blind spot). In contrast, for the Feedback group, combining active training and
      driving-specific feedbacks increased the frequency of blind spot inspection by
      100% (32.3 to 64.9% of verification before changing lanes). CONCLUSIONS: These
      results suggest that simulator training combined with driving-specific feedbacks
      helped older drivers to improve their visual inspection strategies, and that in
      simulator training transferred positively to on-road driving. In order to be
      effective, it is claimed that driving programs should include active practice
      sessions with driving-specific feedbacks. Simulators offer a unique environment
      for developing such programs adapted to older drivers' needs.

PMID- 22385501
TI  - The cost of policy simplification in conservation incentive programs.
AB  - Incentive payments to private landowners provide a common strategy to conserve
      biodiversity and enhance the supply of goods and services from ecosystems. To
      deliver cost-effective improvements in biodiversity, payment schemes must trade
      off inefficiencies that result from over-simplified policies with the
      administrative burden of implementing more complex incentive designs. We examine
      the effectiveness of different payment schemes using field parameterized,
      ecological economic models of extensive grazing farms. We focus on profit
      maximising farm management plans and use bird species as a policy-relevant
      indicator of biodiversity. Common policy simplifications result in a 49-100% loss
      in biodiversity benefits depending on the conservation target chosen. Failure to
      differentiate prices for conservation improvements in space is particularly
      problematic. Additional implementation costs that accompany more complicated
      policies are worth bearing even when these constitute a substantial proportion
      (70% or more) of the payments that would otherwise have been given to farmers.

PMID- 22385500
TI  - Current status and future directions in the management of chronic hepatitis C.
AB  - Hepatitis C virus (HCV) is endemic worldwide, and it causes cirrhosis and other
      complications that often lead to death; nevertheless, our knowledge of the
      disease and its mechanisms is limited. HCV is most common in underdeveloped
      nations, including many in Africa and Asia. The virus is usually transmitted by
      parenteral routes, but sexual, perinatal, and other types of transfer have been
      known to occur. Approximately 80% of individuals who contract hepatitis C develop
      a chronic infection, and very few are able to spontaneously clear the virus.
      Because hepatitis C is asymptomatic in the majority of patients, the presence of
      HCV RNA in the serum is the best diagnostic tool. Although serious complications
      from hepatitis C may not occur for 20 years, 1/5 of chronic patients eventually
      develop life - threatening cirrhosis. More research is needed on the different
      therapy options for the disease, and many factors, most importantly the genotype
      of the virus, must be taken into account before beginning any treatment. As there
      is no vaccine against HCV at present, the most effective and recommended therapy
      is pegylated-interferon-alpha-2a plus ribavirin. While interferon is marginally
      effective as a monotherapy, both adding the moiety and combining it with
      ribavirin have been shown to dramatically increase its potency. While there are
      numerous alternative and complementary medicines available for patients with
      hepatitis C, their efficacy is questionable. Currently, research is being done to
      investigate other possible treatments for hepatitis C, and progress is being made
      to develop a vaccine against HCV, despite the many challenges the virus presents.
      Until such a vaccination is available, prevention and control methods are
      important in containing and impeding the spread of the virus and mitigating its
      deleterious effects on the health of people and communities worldwide.

PMID- 22385502
TI  - Safety of nasal continuous positive airway pressure during nurse-led, single
      clinician neonatal transfers.

PMID- 22385503
TI  - Inhibition of neuronal nitric oxide synthase and soluble guanylate cyclase
      prevents depression-like behaviour in rats exposed to chronic unpredictable mild
      stress.
AB  - Depression is the most common psychiatric disorder. It is well established that
      endogenous nitric oxide (NO) contributes to chronic unpredictable mild stress
      (CUMS)-induced depression. The aim of this study was to investigate brain-derived
      neurotropic factor (BDNF) expression in CUMS-induced depression-like behaviour in
      rats. Rats were exposed to CUMS for 5 weeks. A specific and selective nNOS
      inhibitor, 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg/day, i.p.), and a
      specific soluble guanylate cyclase (sGC) inhibitor, 1H-(1,2,4)oxadiazolo(4,3
      a)quinoxalin-1-one (ODQ; 10 mg/kg/day, i.p.), were administered during CUMS. The
      forced swimming test (FST) was used to assess despair and sucrose consumption,
      and sucrose preference test was used to assess anhedonia that are the main
      symptoms of the depression. We show that both 3-Br-7-NI and ODQ administration
      during CUMS suppressed CUMS-induced, depression-like behavioural changes,
      including reduced sucrose preference, body-weight and locomotor activity as well
      as increased immobility time in the FST. CUMS also significantly decreased BDNF
      protein levels in the CA1 and CA3 regions of the hippocampus, which was reversed
      by 3-Br-7-NI and ODQ administration. Our findings suggest a novel role for nNOS
      and sGC-cGMP in the development of the CUMS model of depression.

PMID- 22385504
TI  - Formation of mixed organic layers by stepwise electrochemical reduction of
      diazonium compounds.
AB  - This work describes the formation of a mixed organic layer covalently attached to
      a carbon electrode. The strategy adopted is based on two successive
      electrochemical reductions of diazonium salts. First, bithiophene phenyl (BTB)
      diazonium salt is reduced using host/guest complexation in a water/cyclodextrin
      (beta-CD) solution. The resulting layer consists of grafted BTB oligomers and
      cyclodextrin that can be removed from the surface. The electrochemical response
      of several outer-sphere redox probes on such BTB/CD electrodes is close to that
      of a diode, thanks to the easily p-dopable oligo(BTB) moieties. When CD is
      removed from the surface, pinholes are created and this diode like behavior is
      lost. Following this, nitrophenyl (NP) diazonium is reduced to graft a second
      component. Electrochemical study shows that upon grafting NP insulating moieties,
      the diode-like behavior of the layer is restored which demonstrates that NP is
      grafted predominately in the empty spaces generated by beta-CD desorption. As a
      result, a mixed BTB/NP organic layer covalently attached to a carbon electrode is
      obtained using a stepwise electrochemical reduction of two diazonium compounds.

PMID- 22385505
TI  - Efavirenz dose reduction in HIV-infected patients.

PMID- 22385506
TI  - Finding and removing highly connected individuals using suboptimal vaccines.
AB  - BACKGROUND: Social networks are often highly skewed, meaning that the vast
      majority of the population has only few contacts whereas a small minority has a
      large number of contacts. These highly connected individuals may play an
      important role in case of an infectious disease outbreak. METHODS: We propose a
      novel strategy of finding and immunizing highly connected individuals and
      evaluate this strategy by computer simulations, using a stochastic, individual
      and network-based simulation approach. A small random sample of the population is
      asked to list their acquaintances, and those who are mentioned most frequently
      are offered vaccination. This intervention is combined with case isolation and
      contact tracing. RESULTS: Asking only 10% of the population for 10 acquaintances
      each and vaccinating the most frequently named people strongly diminishes the
      magnitude of an outbreak which would otherwise have exhausted the available
      isolation units and gone out of control. It is extremely important to immunize
      all identified highly connected individuals. Omitting a few of them because of
      unsuccessful vaccination jeopardizes the overall success, unless non-immunized
      individuals are taken under surveillance. CONCLUSIONS: The strategy proposed in
      this paper is particularly successful because it attacks the very point from
      which the transmission network draws its strength: the highly connected
      individuals. Current preparedness and containment plans for smallpox and other
      infectious diseases may benefit from such knowledge.

PMID- 22385507
TI  - Effect of phosphodiesterase 7 (PDE7) inhibitors in experimental autoimmune
      encephalomyelitis mice. Discovery of a new chemically diverse family of
      compounds.
AB  - Phosphodiesterase (PDE) 7 is involved in proinflammatory processes, being widely
      expressed both on lymphocytes and on certain brain regions. Specific inhibitors
      of PDE7 have been recently reported as potential new drugs for the treatment of
      neurological disorders because of their ability to increase intracellular levels
      of cAMP and thus to modulate the inflammatory process, as a neuroprotective well
      established strategy. Multiple sclerosis is an unmet disease in which pathologies
      on the immune system, T-cells, and specific neural cells are involved
      simultaneously. Therefore, PDE7 inhibitors able to interfere with all these
      targets may represent an innovative therapy for this pathology. Here, we report a
      new chemically diverse family of heterocyclic PDE7 inhibitors, discovered and
      optimized by using molecular modeling studies, able to increase cAMP levels in
      cells, decrease inflammatory activation on primary neural cultures, and also
      attenuate the clinical symptoms in the experimental autoimmune encephalomyelitis
      (EAE) mouse model. These results led us to propose the use of PDE7 inhibitors as
      innovative therapeutic agents for the treatment of multiple sclerosis.

PMID- 22385508
TI  - EDITORIAL: Molecularly targeted treatments for colorectal cancer: advances and
      limitations.

PMID- 22385509
TI  - Synthetic lethality-based therapeutics: perspectives for applications in
      colorectal cancer.
AB  - Over the past two decades, progresses in colorectal cancer treatment have
      significantly improved patient survival and quality of life. However,
      unresectable metastatic colorectal cancer remains virtually incurable, making the
      search for new effective therapeutics mandatory. An important limitation to the
      development of new agents has been the difficulty to exploit mutated tumor
      suppressors or "undruggable" oncogenes as a target. Recently, evidence that
      mutations in tumor suppressors, such as BRCA1/2, make cancer cells highly
      susceptible to inhibitors of a compensatory DNA repair pathway [poly-(ADP-ribose)
      polymerase 1 (PARP1)] has broadened the range of possible therapeutic targets by
      extending it to gene products that are in a "synthetic lethal" relationship with
      oncogenes and tumor suppressors. Inhibition of such targets blocks specific
      buffer-mechanisms that are required for survival in the presence of defined
      oncogenic mutations, but not in their absence. As a consequence, selective
      elimination of mutation-bearing cells results. This approach has led to identify
      compounds that are highly active in the presence of different types of mutated
      tumor suppressors and oncogenes, including DNA repair genes, RAS, and Myc. In
      addition, ongoing studies promise to identify new mechanisms which, when
      pharmacologically interfered with, will selectively eradicate mutated cancer
      cells. Here, we revise and discuss these new aspects of cancer biology and
      highlight their potential applications in colorectal cancer treatment.

PMID- 22385510
TI  - Role of angiogenesis inhibitors in colorectal cancer: sensitive and insensitive
      tumors.
AB  - Angiogenesis is a key factor in the carcinogenesis process. In oncological
      practice, angiogenesis inhibition, mainly through the blockade of the VEGF family
      and its receptors, has been robustly demonstrated to produce clinical benefits
      and, in specific disease subsets such as colorectal cancer, to extend the overall
      survival of treated patients. VEGF is a multifunctional growth factor that
      mediates its functions through cognate receptors on endothelial cells and it has
      been discovered for its capability to induce macromolecule hyperpermeability in
      veins and venules. Several approaches have been taken to target angiogenesis in
      cancer: drugs that target one or more soluble ligands of the VEGF family, drugs
      that selectively inhibit one or more receptors of the VEGF receptor family, and
      drugs that inhibit VEGF receptor(s) among other, non VEGF-related targets. At
      present, two compounds have shown significant clinical activity, bevacizumab,
      Avastin(r) and aflibercept, Zaltrap(r), and only one of these (bevacizumab) has
      so far been registered for use in clinical practice. In the present review, we
      explore and summarize the main features of the angiogenetic process, concerning
      in particular a common and potentially lethal disease as colorectal cancer. We
      overview the molecular pathways that characterize angiogenesis, focusing on VEGF
      family, the current applications and limitations of its blockade in oncology, and
      the hypothetical future perspectives of anti-angiogenic therapy.

PMID- 22385511
TI  - A multi-scale approach to colorectal cancer: from a biochemical- interaction
      signaling-network level, to multi-cellular dynamics of malignant transformation.
      Interplay with mutations and onco-protein inhibitor drugs.
AB  - This review article is part of a special Current Cancer Drug Targets issue
      devoted to colorectal cancer and molecularly targeted treatments. In our paper we
      made an attempt to connect more basic aspects with preclinical, pharmacological /
      therapeutic and clinical aspects. Reconstruction of a Molecular Interaction Map
      (MIM) comprising an important part of the G0 - G1 - S cell cycle transition, was
      a major component of our review. Such a MIM serves also as a convenient /
      organized database of a large set of important molecular events. The frequency of
      mutated / altered signaling-proteins indicates the importance of this signaling
      network region. We have considered problems at different scale levels. Our MIM
      works at a biochemical-interaction level. We have also touched the multi-cellular
      dynamics of normal and aberrant colon crypts. Until recently, dynamic simulations
      at a biochemical or multi-cellular scale level were considered as a sort of
      esoteric approach. We tried to convince the reader, also on the basis of a
      rapidly growing literature, mostly published in high quality journals, that
      suspicion towards simulations should dissipate, as the limitations and advantages
      of their application are better appreciated, opening the door to their permanent
      adoption in everyday research. What is really required is a more
      interdisciplinary mentality and an interdisciplinary approach. The prize is a
      level of understanding going beyond mere intuition.

PMID- 22385512
TI  - Patient-tailored treatments with anti-EGFR monoclonal antibodies in advanced
      colorectal cancer: KRAS and beyond.
AB  - Personalized medicine emphasizes the practice of considering individual patient
      characteristics as opposed to that centered on standards derived from
      epidemiological studies which, by definition, do not take into account the
      variability of individuals within a given population. When applied to oncology,
      personalized medicine is an even more complex concept because it extends the
      variability beyond the individual patient to the individual tumor. Indeed, the
      great genotypic and phenotypic variability (both in primary and metastatic sites
      of cancer) the development of targeted therapies, and the growing availability of
      biological assays complicate the scenario of personalized medicine in the
      oncological field. In this paper we review the results of anti-epidermal growth
      factor receptor (EGFR) monoclonal antibody (mAb) therapy in metastatic colorectal
      cancer (mCRC) in the context of tumor biology, delineating the future prospects
      of patient-tailored medicine in this area. In particular, we deal with EGFR
      inhibition by Cetuximab, a chimeric mouse human IgG1 mAb, and panitumumab, a
      fully human IgG2 mAb. We discuss the clinical impact of anti-EGFR mAbs on wild
      type (WT) KRAS mCRC, also taking into account the feasibility of novel multi
      marker approaches to treatment decision-making, aimed at increasing the
      predictive power of pre-therapy biomarkers. Experimental topics and fields of
      ongoing research, such as targeting microRNAs (miRNAs) with novel anticancer
      drugs and epigenetics in CRC are also addressed.

PMID- 22385513
TI  - DNA damage response pathways and cell cycle checkpoints in colorectal cancer:
      current concepts and future perspectives for targeted treatment.
AB  - Although several drugs have been designed in the last few years to target
      specific key pathways and functions in colorectal cancer (CRC), the backbone of
      CRC treatment is still made up of compounds which rely on DNA damage to
      accomplish their role. DNA damage response (DDR) and checkpoint pathways are
      intertwined signaling networks that arrest cell cycle, recognize and repair
      genetic mistakes which arise during DNA replication and transcription, as well as
      through the exposure to chemical and physical agents that interact with nucleic
      acids. The good but highly variable activity of DNA damaging agents in the
      treatment of CRC suggests that intrinsic alterations in DDR pathways and cell
      cycle checkpoints may contribute differentially to the way cancer cells react to
      DNA damage. In the present review, our aim is to depict the recent advances in
      understanding the molecular basis of the activity of DNA damaging agents used for
      the treatment of CRC. We focus on the known and potential drug targets that are
      part of these complex and intertwined pathways. We describe the potential role of
      the checkpoints in CRC, and how their pharmacological manipulation could lead to
      chemopotentiation or synergism with currently used drugs. Novel therapeutic
      agents playing a role in DDR and checkpoint inhibition are assessed. We discuss
      the possible rationale for combining PARP inhibition with DNA damaging agents,
      and we address the link between DDR and EGFR pathways in CRC.

PMID- 22385514
TI  - Second-generation tyrosine kinase inhibitors as first-line treatment strategy in
      newly diagnosed chronic phase chronic myeloid leukemia patients.
AB  - Recent results of phase II trials which used dasatinib or nilotinib as single
      agent, or phase III trials comparing second-generation tyrosine kinase inhibitors
      to imatinib, showed greater potency of these two inhibitors in newly diagnosed
      chronic myeloid leukemia (CML) patients in chronic phase (CP). In the present
      review we detail and summarize clinical results of both agents as first-line
      therapeutic strategy, and also discuss on critical points emerged from the last
      follow-up of trials comparing new generation tyrosine kinase inhibitors with
      imatinib. In terms of safety, dasatinib and nilotinib have shown favorable
      toxicity profile, with peculiar and distinct pattern of adverse events. Based on
      these results, USA FDA approved both drugs as first-line treatment in newly
      diagnosed CML: now several therapeutic strategies are available to treat patients
      at onset of disease. Longer follow-up is however needed to prove the advantages
      of faster and deeper responses in terms of disease progression compared to
      imatinib.

PMID- 22385515
TI  - Structural comparison of the interaction of tubulin with various ligands
      affecting microtubule dynamics.
AB  - Microtubules (MTs), which are highly dynamic assemblies of the protein tubulin,
      play important and diverse roles in eukaryotic cells. MT dynamics are regulated
      during the cell cycle by interacting with a large number of endogenous cellular
      regulators. In addition, many anti-tumour drugs and natural ligands that interact
      directly with tubulin are able to either stabilise or destabilise MTs and to
      disrupt the normal dynamics. Herein, we compare the structures of tubulin when
      complexed with different ligands in order to analyse: (i) various binding-sites
      of the protein and different positions of ligands within the microtubule (ii) the
      diverse effect on the microtubule dynamics. The structures and data given are
      essential for understanding tubulin-ligand interactions and their influence on
      the regulation of the microtubule system.

PMID- 22385517
TI  - Human polyomaviruses identification by logic mining techniques.
AB  - BACKGROUND: Differences in genomic sequences are crucial for the classification
      of viruses into different species. In this work, viral DNA sequences belonging to
      the human polyomaviruses BKPyV, JCPyV, KIPyV, WUPyV, and MCPyV are analyzed using
      a logic data mining method in order to identify the nucleotides which are able to
      distinguish the five different human polyomaviruses. RESULTS: The approach
      presented in this work is successful as it discovers several logic rules that
      effectively characterize the different five studied polyomaviruses. The
      individuated logic rules are able to separate precisely one viral type from the
      other and to assign an unknown DNA sequence to one of the five analyzed
      polyomaviruses. CONCLUSIONS: The data mining analysis is performed by considering
      the complete sequences of the viruses and the sequences of the different gene
      regions separately, obtaining in both cases extremely high correct recognition
      rates.

PMID- 22385518
TI  - Pikaia gracilens Walcott, a stem-group chordate from the Middle Cambrian of
      British Columbia.
AB  - The Middle Cambrian Pikaia gracilens (Walcott) has an iconic position as a
      Cambrian chordate, but until now no detailed description has been available. Here
      on the basis of the 114 available specimens we review its anatomy, confirm its
      place in the chordates and explore with varying degrees of confidence its
      relationships to both extant and extinct chordates and other deuterostomes. The
      body of Pikaia is fusiform, laterally compressed and possesses about 100
      myomeres. The head is small, bilobed and bears two narrow tentacles. There is no
      evidence for eyes. Apart from a thin dorsal fin (without finrays) and a series of
      at least nine bilaterally arranged appendages with possible pharyngeal pores at
      the anterior end, there are no other external features. In addition to the
      musculature the internal anatomy includes an alimentary canal, the anterior of
      which forms a prominent lenticular unit that is almost invariably preserved in
      positive relief. The cavity is interpreted as pharyngeal, implying that the mouth
      itself was almost terminal. The posterior extension of the gut is unclear
      although the anus appears to have been terminal. The most prominent internal
      structure is a reflectively preserved unit, possibly hollow, termed here the
      dorsal organ. Although formerly interpreted as a notochord its position and size
      make this less likely. Its original function remains uncertain, but it could have
      formed a storage organ. Ventral to the dorsal organ a narrower strand of tissue
      is interpreted as representing the nerve chord and notochord. In addition to
      these structures, there is also evidence for a vascular system, including a
      ventral blood vessel. The position of Pikaia in the chordates is largely based on
      the presence of sigmoidal myomeres, and the more tentative identification of a
      notochord. In many other respects, Pikaia differs from the expected nature of
      primitive chordates, especially as revealed in amphioxus and the Cambrian record
      (including Cathaymyrus, Haikouichthys, Metaspriggina, Myllokunmingia, and
      Zhongxiniscus). Whilst the possibility that Pikaia is simply convergent on the
      chordates cannot be dismissed, we prefer to build a scenario that regards Pikaia
      as the most stem-ward of the chordates with links to the phylogenetically
      controversial yunnanozoans. This hypothesis has implications for the evolution of
      the myomeres, notochord and gills. Finally, the wealth of material of Pikaia
      indicates that, although by definition there must be some sort of taphonomic
      imprint, the consistency of preservational details allows a reliable
      reconstruction of the anatomy and does not significantly erode phylogenetically
      relevant characters.

PMID- 22385519
TI  - Diabetes, coeliac disease, multiple sclerosis and chronic arthritis in first
      degree relatives of patients with juvenile idiopathic arthritis.
AB  - AIM: To evaluate the occurrence of autoimmune diseases in first-degree relatives
      of children with juvenile idiopathic arthritis (JIA) and to compare the figures
      with published population data. MATERIALS AND METHODS: Families of the 362
      children with recently diagnosed JIA admitted to Rheumatism Foundation Hospital,
      Finland, from 1996 to 2001 were contacted by questionnaires regarding autoimmune
      diseases in family members. Data were collected on type 1 diabetes, coeliac
      disease, multiple sclerosis and chronic arthritis, consisting mainly of JIA,
      rheumatoid arthritis, spondyloarthropathy or psoriatic arthritis. RESULTS: In
      all, 21.4% of the 355 families with a patient with JIA had members with type 1
      diabetes, coeliac disease, multiple sclerosis or chronic arthritis. Thirty-three
      mothers and 23 fathers had type 1 diabetes, coeliac disease, multiple sclerosis
      or chronic arthritis in 15.2% (95% CI 11.6-19.4) of the families, and 23 mothers
      and 15 fathers had chronic arthritis in 10.7% (95% CI 7.7-14.5) of the families.
      When compared with available research data, the prevalences of rheumatoid
      arthritis, spondyloarthropathy, psoriatic arthritis, paediatric type 1 diabetes
      and JIA (in siblings) were increased in JIA families. Coeliac disease was as
      prevalent as in the population. CONCLUSION: Autoimmune diseases cluster in
      families with a child with JIA.

PMID- 22385520
TI  - Electrochemical solid-state phase transformations of silver nanoparticles.
AB  - Adenosine triphosphate (ATP)-capped silver nanoparticles (ATP-Ag NPs) were
      synthesized by reduction of AgNO(3) with borohydride in water with ATP as a
      capping ligand. The NPs obtained were characterized using transmission electron
      microscopy (TEM), UV-vis absorption spectroscopy, X-ray diffraction, and energy
      dispersive X-ray analysis. A typical preparation produced ATP-Ag NPs with
      diameters of 4.5 +/- 1.1 nm containing ~2800 Ag atoms and capped with 250 ATP
      capping ligands. The negatively charged ATP caps allow NP incorporation into
      layer-by-layer (LbL) films with poly(diallyldimethylammonium) chloride at thiol
      modified Au electrode surfaces. Cyclic voltammetry in a single-layer LbL film of
      NPs showed a chemically reversible oxidation of Ag NPs to silver halide NPs in
      aqueous halide solutions and to Ag(2)O NPs in aqueous hydroxide solutions. TEM
      confirmed that this takes place via a redox-driven solid-state phase
      transformation. The charge for these nontopotactic phase transformations
      corresponded to a one-electron redox process per Ag atom in the NP, indicating
      complete oxidation and reduction of all Ag atoms in each NP during the
      electrochemical phase transformation.

PMID- 22385521
TI  - The incommensurately modulated structures of the perovskites NaCeMnWO6 and
      NaPrMnWO6.
AB  - The structures of the doubly ordered perovskites NaCeMnWO(6) and NaPrMnWO(6),
      with rock salt ordering of the Mn(2+) and W(6+)B-site cations and layered
      ordering of the Na(+) and (Ce(3+)/Pr(3+)) A-site cations, have been studied by
      transmission electron microscopy, electron diffraction, neutron and synchrotron X
      ray powder diffraction. Both compounds possess incommensurately modulated crystal
      structures. In NaCeMnWO(6) the modulation vector (with reference to the ideal
      ABX(3) perovskite subcell) is q ~ 0.067a* (~58.7 A) and in NaPrMnWO(6)q ~ 0.046a*
      (~85.3 A). In both compounds the superstructures are primarily the two
      dimensional chessboard type, although some crystals of NaCeMnWO(6) were found
      with one-dimensional stripes. In some crystals of NaPrMnWO(6) there is a
      coexistence of chessboards and stripes. Modeling of neutron diffraction data
      shows that octahedral tilting plays an important role in the structural
      modulation.

PMID- 22385522
TI  - Allelic expression analysis of the osteoarthritis susceptibility locus that maps
      to MICAL3.
AB  - BACKGROUND: A genome-wide association scan with subsequent replication study that
      involved over 67,000 individuals of European ancestry has produced evidence of
      association of single nucleotide polymorphism rs2277831 to primary osteoarthritis
      (OA) with a P-value of 2.9 * 10(-5). rs2277831, an A/G transition, is located in
      an intron of MICAL3. This gene is located on chromosome 22q11.21 and the
      association signal encompasses two additional genes, BCL2L13 and BID. It is
      becoming increasingly apparent that many common complex traits are mediated by
      cis-acting regulatory polymorphisms that influence, in a tissue-specific manner,
      gene expression or transcript stability. METHODS: We used total and allelic
      expression analysis to assess whether the OA association to rs2277831 is mediated
      by an influence on MICAL3, BCL2L13 or BID expression. Using RNA extracted from
      joint tissues of 60 patients who had undergone elective joint replacement
      surgery, we assessed whether rs2277831 correlated with allelic expression of
      either of the three genes by: 1) measuring the expression of each gene by
      quantitative PCR and then stratifying the data by genotype at rs2277831 and 2)
      accurately discriminating and quantifying the mRNA synthesised from the alleles
      of OA patients using allelic-quantitative PCR. RESULTS: We found no evidence for
      a correlation between gene expression and genotype at rs2277831, with P-values of
      0.09 for BCL2L13, 0.07 for BID and 0.33 for MICAL3. In the allelic expression
      analysis we observed several examples of significant (p < 0.05) allelic
      imbalances, with an allelic expression ratio of 2.82 observed in BCL2L13 (P =
      0.004), 2.09 at BID (P = 0.001) and the most extreme case being at MICAL3, with
      an allelic expression ratio of 5.47 (P = 0.001). However, there was no
      correlation observed between the pattern of allelic expression and the genotype
      at rs2277831. CONCLUSIONS: In the tissues that we have studied, our data do not
      support our hypothesis that the association between rs2277831 and OA is due to
      the effect this SNP has on MICAL3, BCL2L13 or BID gene expression. Instead, our
      data point towards other functional effects accounting for the OA associated
      signal.

PMID- 22385523
TI  - Identification of tumor epithelium and stroma in tissue microarrays using texture
      analysis.
AB  - BACKGROUND: The aim of the study was to assess whether texture analysis is
      feasible for automated identification of epithelium and stroma in digitized tumor
      tissue microarrays (TMAs). Texture analysis based on local binary patterns (LBP)
      has previously been used successfully in applications such as face recognition
      and industrial machine vision. TMAs with tissue samples from 643 patients with
      colorectal cancer were digitized using a whole slide scanner and areas
      representing epithelium and stroma were annotated in the images. Well-defined
      images of epithelium (n = 41) and stroma (n = 39) were used for training a
      support vector machine (SVM) classifier with LBP texture features and a contrast
      measure C (LBP/C) as input. We optimized the classifier on a validation set (n =
      576) and then assessed its performance on an independent test set of images (n =
      720). Finally, the performance of the LBP/C classifier was evaluated against
      classifiers based on Haralick texture features and Gabor filtered images.
      RESULTS: The proposed approach using LPB/C texture features was able to correctly
      differentiate epithelium from stroma according to texture: the agreement between
      the classifier and the human observer was 97 per cent (kappa value = 0.934, P <
      0.0001) and the accuracy (area under the ROC curve) of the LBP/C classifier was
      0.995 (CI95% 0.991-0.998). The accuracy of the corresponding classifiers based on
      Haralick features and Gabor-filter images were 0.976 and 0.981 respectively.
      CONCLUSIONS: The method illustrates the capability of automated segmentation of
      epithelial and stromal tissue in TMAs based on texture features and an SVM
      classifier. Applications include tissue specific assessment of gene and protein
      expression, as well as computerized analysis of the tumor microenvironment.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4123422336534537.

PMID- 22385524
TI  - The balance of feelings: vestibular modulation of bodily sensations.
AB  - The vestibular system processes information about head movement and orientation.
      No unimodal vestibular cortex has been identified in the mammalian brain. Rather,
      vestibular inputs are combined with many other sensory signals in the cortex.
      This arrangement suggests that vestibular input could influence processing in
      other sensory modalities. Here we show that vestibular stimulation differentially
      modulates two submodalities of the somatosensory system, increasing sensitivity
      to tactile input, and independently reducing sensitivity to nociceptive input.
      These modulations of touch and pain can clearly be distinguished from supramodal
      attentional effects of vestibular stimulation, because they are bilateral and
      operate in different directions. Outside the artificial conditions of laboratory
      stimulation, the vestibular system codes movements of the head, indicating a new
      relation between the body and the external world. We suggest the vestibular
      system participates in a form of sensory signal management, changing the balance
      between the various sensory systems as the relation between the body and the
      external environment changes. This sensory rebalancing may be a crucial element
      in the brain's capacity to reorient towards novel or salient features in the
      environment.

PMID- 22385525
TI  - Node positive melanoma--a positive note?

PMID- 22385526
TI  - The role of sentinel lymph node biopsy in patients with thick melanoma. A single
      centre experience.
AB  - AIMS: To evaluate the role, if any, of sentinel lymph node mapping (SLNM) with
      biopsy (SLNB) in patients with thick cutaneous melanoma. METHODS: Consecutive
      patients with thick (Breslow >=4 mm) cutaneous melanoma, undergoing SLNB were
      identified from a departmental database comprising 550 patients in total from
      2000 to 2010. Factors examined included demographic data, histological subtype,
      site and depth of lesion, percentage of positive SLNs, regional recurrence in the
      setting of a negative SLNB result (false-negative rate), complications, further
      lymphadenectomy, and follow-up (disease free and overall survival), where
      available. RESULTS: Sixty-four eligible patients (37 men, 27 women) underwent
      primary excision and SLNM. Median patient age was 59 years (range 8-82 years).
      Mean Breslow depth was 7 mm (range 4-19 mm). Thirty melanomas were located on the
      limbs, 19 on the head and neck and 15 on the trunk. Twenty-three (35%) were
      ulcerated. Of the 57 patients who had a sentinel node identified, 18 (31%) had
      metastatic melanoma identified. The mean survival time for patients with a
      negative SLN was 79 months versus 18 months for those with a positive node.
      Patients with a negative SLN have a 5 year disease free survival of 79% versus
      11% (p < 0.001) and an overall 5 year survival rate of 85% versus 32% when
      compared to node positive patients. CONCLUSIONS: The status of the SLN is
      predictive of disease recurrence and overall survival in patients with a thick
      primary cutaneous melanoma. This modality should be employed, where applicable,
      in this cohort of patients.

PMID- 22385527
TI  - Evaluation of post operative shoulder tip pain in low pressure versus standard
      pressure pneumoperitoneum during laparoscopic cholecystectomy.
AB  - INTRODUCTION: Insufflation of carbon dioxide during laparoscopic cholecystectomy
      leads to postoperative shoulder tip pain. The origin of shoulder pain is commonly
      assumed to be due to overstretching of the diaphragmatic muscle fibres owing to a
      high carbon dioxide pressure. AIMS: To study the frequency and intensity of post
      operative shoulder tip pain in laparoscopic cholecystectomy and compare low and
      standard pressure pneumoperitoneum during laparoscopic cholecystectomy with
      respect to post operative shoulder tip pain. METHODS: Patients admitted in the
      department of surgery for elective cholecystectomy were enrolled in the study.
      The patients were randomly allocated to two groups (group A and group B). In
      group A (n = 50), low pressure pneumoperitoneum (8 mm Hg) and in group B (n =
      50), standard pressure pneumoperitoneum (14 mm Hg) was generated during
      laparoscopic cholecystectomy. Postoperative shoulder tip pain was assessed at 4,
      8 and 24 h after operation by the Visual Analogue Scale of Pain. RESULTS: 14
      patients (28%) in group B complained of post operative shoulder tip pain as
      compared to only 5 patients (10%) in group A. The mean intensity of post
      operative shoulder tip pain assessed by visual analogue scoring scale at 4, 8 and
      24 h was less in group A as compared to group B, although statistical
      significance was seen only at 4 h. Analgesic requirements and the mean length of
      post operative stay in the hospital were also less in group A as compared to
      group B. CONCLUSION: Low pressure laparoscopic cholecystectomy (LPLC)
      significantly decreases the frequency and intensity of postoperative shoulder tip
      pain. LPLC decreases the demand for postoperative analgesics, decreases
      postoperative hospital stay and hence improves the quality of life in the early
      stage of postoperative rehabilitation.

PMID- 22385528
TI  - The role of pre-operative assessment and ringfencing of services in the control
      of methicillin resistant Staphlococcus aureus infection in orthopaedic patients.
AB  - BACKGROUND: MRSA is a major economic and health issue internationally and as such
      is of particular importance in the appropriate management of orthopaedic
      patients. Bone, joint and implant infection can lead to unfavourable outcomes
      with a long protracted in hospital stay inevitable. The cost for the patient, the
      hospital and society are substantial. MATERIALS AND METHODS: This study was a
      review of a prospectively maintained database from our unit over three time
      points from 2005 to 2007. At each time point a new infection control measure was
      implemented in an effort to reduce MRSA infections. Total rates of MRSA infection
      and colonisation in all orthopaedic patients were recorded, before and after
      separation of trauma and elective services, and after the introduction of a
      screening pre assessment clinic. RESULTS: 12259 orthopaedic patients were
      reviewed over the three years. The mean age of MRSA infected patients was 71. A
      higher proportion of female patients were infected than male patients. The mean
      length of stay for infected patients was 23.4 days. The rate of infection dropped
      from 0.49% in 2005 to 0.24%in 2007. After the introduction of these measures
      there was a substantial reduction in organ space and deep tissue infections.
      CONCLUSION: The separation of emergency and elective orthopaedic services coupled
      with effective pre-operative screening has resulted in a significant reduction in
      MRSA infection despite an ever increasing prevalance.

PMID- 22385529
TI  - Imaging the spine for tumour and trauma--a national audit of practice in Irish
      hospitals.
AB  - BACKGROUND AND PURPOSE: The provision of appropriate spinal imaging in cases of
      acute injury as a consequence of trauma or tumour is becoming ever more
      challenging. This study assessed the use of multimodal radiological
      investigations in the management of spinal cord compression as a result of trauma
      and metastatic cancer in all major Irish hospitals. METHODS: We conducted a
      questionnaire of thirty four hospitals in an effort to assess the provision of
      these services to patients with possible spinal cord compromise. In all public
      hospitals the Emergency Department and/or the Orthopaedic Registrars were
      contacted and asked a series of questions relating to spinal clearance, spinal
      clearance protocols, CT and MRI scanning facilities and on site orthopaedic
      services. RESULTS: All centres participated in the study. 67.64% of centres
      routinely used a protocol in spinal clearance. In 87% of hospitals the Emergency
      department were responsible for clearing the spine. 85.3% of hospitals had CT
      availability during normal working hours (9-5) dropping to 47% availability after
      hours. MRI was available in 50% of hospitals, with surprisingly just two centres
      providing out of hours MRI imaging services. CONCLUSION: The provision of
      radiological services in the management of suspected spinal injuries in Irish
      hospitals is inadequate in comparison to international best practice. This is
      most marked in relation to CT and MRI.

PMID- 22385530
TI  - Assessment of calf volume in Congenital Talipes Equinovarus by computer analysed
      digital photography.
AB  - The development of evidence-based approaches to the Congenital Talipes
      Equinovarus (CTEV) is impaired by the diversity of assessment techniques
      available, many of which have not been validated. Highly objective evaluation
      techniques that reflect the deformity and permit comparison between studies may
      lack the necessary link to functional features that are paramount to the patient,
      namely pain and mobility. Calf wasting is an acknowledged but little investigated
      component of the pathology. The rapid evolution of digital photography and
      computerised analytical techniques has yielded an opportunity to explore their
      role in the assessment of this common paediatric Orthopaedic pathology. This
      study presents the use of a cost-effective digital photographic assessment
      technique of maximal calf circumference and calf volume. These indices reflect
      the muscular development in the calf and therefore have significance in the
      functional assessment of CTEV and may represent an index of severity.
      Subjectivity has been limited by computerisation of the analysis process. The
      technique could easily be adapted to other volumetric analyses.

PMID- 22385531
TI  - Perioperative multimodal optimisation in patients undergoing surgery for
      fractured neck of femur.
AB  - INTRODUCTION: Enhanced Recovery after Surgery protocols are associated with
      reduced length of stay and morbidity in patients undergoing major surgery. The
      aim of this audit was to assess the impact of a multimodal optimisation protocol
      in patients admitted with fractured neck of femur. PATIENTS AND METHODS: A
      multimodal optimisation protocol was introduced for the care of patients with
      proximal femoral fractures. The short-term effects of the optimised perioperative
      care programme was assessed and compared with the conventional perioperative care
      before the intervention. RESULTS: A total of 232 patients were included in this
      audit, 117 optimised care and 115 conventional care. Patients were similar with
      regards to age, gender, domicile, mental status and the type of operation. The
      optimised group suffered from fewer post-operative complications (36 out of 117
      vs 48 out of 115, P = 0.04, Chi square test). There was no significant difference
      between two groups with regards to the length of hospital stay and 30-day
      mortality. CONCLUSION: Multimodal optimisation may be associated with a decline
      in post-operative morbidity in patients with proximal hip fracture. It does not
      have any significant impact on the length of hospital stay and 30-day mortality.

PMID- 22385532
TI  - Combined laparoscopic anterior resection and right hemicolectomy for synchronous
      colorectal tumours: how to retrieve both specimens at the same time through a
      transverse incision.

PMID- 22385533
TI  - Nanotechnological and biotechnological strategies for drug delivery.

PMID- 22385534
TI  - Disease-responsive drug delivery: the next generation of smart delivery devices.
AB  - With the advent of highly potent and cytotoxic drugs, it is increasingly critical
      that they be targeted and released only in cells of diseased tissues, while
      sparing physiologically normal neighbors. Simple ligand-based targeting of drug
      carriers, although promising, cannot always provide the required specificity to
      achieve this since often normal cells also express significant levels of the
      targeted receptors. Therefore, stimuli-responsive delivery systems are being
      explored to allow drug release from nano- and microcarriers and implantable
      devices, primarily in the presence of physiological or disease-specific
      pathophysiological signals. Designing smart biomaterials that respond to
      temperature or pH changes, protein and ligand binding, disease-specific
      degradation, e.g. enzymatic cleavage, has become an integral part of this
      approach. These strategies are used in combination with nano- and microparticle
      systems to improve delivery efficiency through several routes of administration,
      and with injectable or implantable systems for long term controlled release. This
      review focuses on recent developments in stimuli-responsive systems, their
      physicochemical properties, release profiles, efficacy, safety and
      biocompatibility, as well as future perspectives.

PMID- 22385535
TI  - Can a formally zwitterionic rhodium(I) complex emulate the charge density of a
      cationic rhodium(I) complex? A combined synchrotron X-ray and theoretical charge
      density study.
AB  - The molecular electron densities of structurally related cationic ([(kappa(2)-3
      P(i)Pr(2)-2-NMe(2)-indene)Rh(COD)](CF(3)SO(3)), [1c](CF(3)SO(3))) and formally
      zwitterionic ([(kappa(2)-3-P(i)Pr(2)-2-NMe(2)-indenide)Rh(COD)], 1z) complexes
      were accurately determined using synchrotron bright-source X-ray radiation at 30
      K followed by multipolar refinement (COD = eta(4)-1,5-cyclooctadiene). The
      densities were also obtained from density functional theory calculations with a
      large, locally dense basis set. A 28-electron ([Ar]3d(10)) core of the Rh atom
      was modeled by an effective core potential to obtain a density that was then
      augmented with relativistic cores according to the Keith-Frisch approximation.
      Calculations were performed at the experimental geometry and after vacuum-phase
      geometry optimization starting from the experimental geometry. Experimental and
      calculated geometries and electron-density distributions show that the electron
      density and electronic structure in the region of the Rh center are not
      significantly altered by protonation of the aromatic ring and that formal removal
      of CF(3)SO(3)H from [1c](CF(3)SO(3)) affords a complex 1z possessing substantial
      zwitterionic character (with a charge separation of ca. 0.9 electronic charge)
      featuring a negatively charged aromatic indenide framework. Further, the
      molecular electrostatic potentials of 1c and 1z exhibit similar topography around
      the metal, despite being drastically different in the vicinity of the indene or
      indenide portion of the cation (1c) and zwitterion (1z), respectively.
      Collectively, these observations obtained from high-level experimental and
      theoretical electron-density analysis confirm, for the first time, that
      appropriately designed zwitterionic complexes can effectively emulate the charge
      distribution found within ubiquitous cationic platinum-group metal catalyst
      complexes, in keeping with recent catalytic investigations.

PMID- 22385536
TI  - Variation between seated and standing/walking postures among male and female call
      centre operators.
AB  - BACKGROUND: The dose and time-pattern of sitting has been suggested in public
      health research to be an important determinant of risk for developing a number of
      diseases, including cardiovascular disorders and diabetes. The aim of the present
      study was to assess the time-pattern of seated and standing/walking postures
      amongst male and female call centre operators, on the basis of whole-shift
      posture recordings, analysed and described by a number of novel variables
      describing posture variation. METHODS: Seated vs. standing/walking was recorded
      using dichotomous inclinometers throughout an entire work shift for 43 male and
      97 female call centre operators at 16 call centres. Data were analysed using an
      extensive set of variables describing occurrence of and switches between seated
      and standing/walking, posture similarity across the day, and compliance with
      standard recommendations for computer work. RESULTS: The majority of the
      operators, both male and female, spent more than 80% of the shift in a seated
      posture with an average of 10.4 switches/hour between seated and standing/walking
      or vice versa. Females spent, on average, 11% of the day in periods of sustained
      sitting longer than 1 hour; males 4.6% (p = 0.013). Only 38% and 11% of the
      operators complied with standard recommendations of getting an uninterrupted
      break from seated posture of at least 5 or 10 minutes, respectively, within each
      hour of work. Two thirds of all investigated variables showed coefficients of
      variation between subjects above 0.5. Since work tasks and contractual break
      schedules were observed to be essentially similar across operators and across
      days, this indicates that sedentary behaviours differed substantially between
      individuals. CONCLUSIONS: The extensive occurrence of uninterrupted seated work
      indicates that efforts should be made at call centres - and probably in other
      settings in the office sector - to introduce more physical variation in terms of
      standing/walking periods during the work day. We suggest the metrics used in this
      study for quantifying variation in sedentary behaviour to be of interest even for
      other dichotomous exposures relevant to occupational and public health, for
      instance physical activity/inactivity.

PMID- 22385537
TI  - Identifying biological landmarks using a novel cell measuring image analysis
      tool: Cell-o-Tape.
AB  - BACKGROUND: The ability to quantify the geometry of plant organs at the cellular
      scale can provide novel insights into their structural organization. Hitherto
      manual methods of measurement provide only very low throughput and subjective
      solutions, and often quantitative measurements are neglected in favour of a
      simple cell count. RESULTS: We present a tool to count and measure individual
      neighbouring cells along a defined file in confocal laser scanning microscope
      images. The tool allows the user to extract this generic information in a
      flexible and intuitive manner, and builds on the raw data to detect a significant
      change in cell length along the file. This facility can be used, for example, to
      provide an estimate of the position of transition into the elongation zone of an
      Arabidopsis root, traditionally a location sensitive to the subjectivity of the
      experimenter. CONCLUSIONS: Cell-o-tape is shown to locate cell walls with a high
      degree of accuracy and estimate the location of the transition feature point in
      good agreement with human experts. The tool is an open source ImageJ/Fiji macro
      and is available online.

PMID- 22385539
TI  - Alternative approaches to cervical cancer screening for developing countries.
AB  - Cervical cancer remains the most common cancer among women living in developing
      countries, largely because of the failure either to initiate or sustain effective
      cervical-cancer screening programmes. This potentially preventable and curable
      cancer continues to cause high mortality among relatively young women residing in
      low-resource countries. Cytology as a screening test, linked with a robust
      healthcare infrastructure, has significantly affected cervical cancer prevention
      in countries that have had sufficient resources to establish and sustain well
      conducted programmes. The failure to establish such programmes has stimulated a
      large body of research into alternative screening tests and approaches to
      cervical-cancer prevention. Two of the most recent research methods have been
      visual inspection with acetic acid and molecular testing for high-risk types of
      human papillomavirus deoxyribonucleic acid. Visual inspection with acetic acid
      has shown a great deal of promise in cross-sectional studies; however, in
      randomised-controlled trials, it has been shown to be significantly less
      effective in reducing cervical cancer or its precursors. The development of point
      of-care human papillomavirus or other highly sensitive tests for the prevention
      of cervical cancer is imperative. It has also been clearly shown that linking
      testing or screening to treatment (so-called 'screen and treat') without the
      intervention of colposcopy or the need for sophisticated laboratories may
      potentially prevent cervical cancer in large numbers of women.

PMID- 22385540
TI  - Medications that lower low-density lipoprotein (LDL) cholesterol and non-high
      density lipoprotein (non-HDL) cholesterol.

PMID- 22385538
TI  - Photoswitchable nanoparticles for triggered tissue penetration and drug delivery.
AB  - We report a novel nanoparticulate drug delivery system that undergoes reversible
      volume change from 150 to 40 nm upon phototriggering with UV light. The volume
      change of these monodisperse nanoparticles comprising spiropyran, which undergoes
      reversible photoisomerization, and PEGylated lipid enables repetitive dosing from
      a single administration and enhances tissue penetration. The photoswitching
      allows particles to fluoresce and release drugs inside cells when illuminated
      with UV light. The mechanism of the light-induced size switching and triggered
      release is studied. These particles provide spatiotemporal control of drug
      release and enhanced tissue penetration, useful properties in many disease states
      including cancer.

PMID- 22385541
TI  - The use of lipopheresis in the practice of clinical lipidology.

PMID- 22385542
TI  - Polish Lipid Association--a strong response to the problem of lipid disorders in
      Poland and Central and Eastern Europe.

PMID- 22385543
TI  - Genotype-phenotype correlation related to lipid profile in beta-thalassemia major
      and intermedia in southern Iran.
AB  - BACKGROUND: Beta-thalassemia is commonly associated with lipid abnormalities. The
      aim of this study was to search for links between these lipid alterations and
      different types of beta-thalassemia mutations. METHODS: The study, conducted from
      2009 to 2010, included 100 patients with thalassemia major (TM) and 100 with
      thalassemia intermedia (TI). The control group was selected from 100 age- and sex
      matched healthy individuals with normal hematologic indices. Serum lipid
      profiles, including total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG),
      were determined and their relationship with different covariates, including
      different beta-globin gene mutations, was analyzed. RESULTS: Patients with TI had
      significantly lower values for TC, LDL-C, HDL-C, and LDL-C/HDL-C ratio compared
      with TM patients and controls (P < .001). TG was greater in TM compared with TI
      patients (P = .001) and healthy individuals (P = .007). Hemoglobin was positively
      associated with TC (P < .001), LDL-C (P = .004), and HDL-C (P = .01) in TM
      patients. Splenectomy correlated with greater TC (P = .006) and LDL-C (P = .01)
      in TI patients, but only with greater LDL-C in TM patients (P = .02). The average
      amounts of TC and LDL-C were lower in persons with the beta(0)/beta(0) mutation
      compared with the beta(+)/beta(+) group. CONCLUSION: Lower amounts of TG, TC, LDL
      C, and HDL-C were seen in TI patients compared with TM patients and healthy
      individuals. The severity of the genotype (ie, beta(0) type mutations compared
      with beta(+) type mutations) affected the degree of reduction in serum lipids.

PMID- 22385545
TI  - A systematic review on evidence of the effectiveness and safety of a wax-matrix
      niacin formulation.
AB  - Niacin is a uniquely efficacious therapy in the treatment of dyslipidemia because
      of its broad spectrum of beneficial effects on every aspect of the lipid profile
      and because it has been shown to reduce both total mortality and coronary death.
      However, niacin therapy is hindered by its side-effect profile, which appears to
      be dependent on its formulation with immediate-release niacin, associated with a
      greater incidence of flushing, and sustained-release niacin, associated with
      greater liver function test (LFT) abnormalities and hepatotoxicity. One such
      sustained-release niacin nutritional supplement formulation, Endur-acin
      (Endurance Products Company, Tigard, OR), claims to have clinical evidence to
      support its use in the treatment of dyslipidemias, which prompted us to
      systematically review the literature. We identified four published papers in
      which the authors reported the results of two separate clinical trials and one
      pharmacokinetic study that fulfilled the inclusion criteria and were included in
      this review. Endur-acin significantly reduced total cholesterol, low-density
      lipoprotein cholesterol, and total cholesterol/high-density lipoprotein
      cholesterol ratio with mean reductions up to 19%, 26%, and 20%, respectively, at
      a dose of 2000 mg/day. Less-impressive benefits were also seen with high-density
      lipoprotein cholesterol (+10%) and serum triglycerides (-23%). Mean LFT
      elevations of up to 1.6-fold were seen at the 2000 mg per day dose, however, not
      exceeding three times the upper limit of normal, with abnormal results occurring
      at similar frequency in placebo and one patient experiencing marked
      gastrointestinal symptoms and a hepatitis-like syndrome with reversible elevated
      LFT. Short-term randomized controlled trials suggest Endur-acin is effective in
      modifying serum lipids, although study limitations prevent a comprehensive
      evaluation of safety.

PMID- 22385544
TI  - Difference between calculated and direct-measured low-density lipoprotein
      cholesterol in subjects with diabetes mellitus or taking lipid-lowering
      medications.
AB  - OBJECTIVE: We evaluated factors that caused differences between calculated low
      density lipoprotein cholesterol (C-LDL-C) and direct-measured LDL-C (D-LDL-C) and
      compared them in subjects with diabetes mellitus (DM) or taking lipid-lowering
      medications. METHODS: 21,452 subjects (9,177 women, 12,275 men; 8.1% with DM and
      8.5% on lipid-lowering medications) were included in the analysis. Participants
      were classified into 3 groups, i.e., group 1: the subjects without DM and not on
      lipid-modifying drugs (n = 18,287), group 2: without DM and on lipid-modifying
      drugs (n = 1,423), and group 3: with DM (n = 1,742). LDL-C concentrations were
      either directly measured by a homogenous method or calculated by Friedewald
      formula. RESULTS: There was a significant correlation between C-LDL-C and D-LDL-C
      (r = 0.966, P < .001). The absolute values of the differences between two LDL-C
      values were 7.0 +/- 6.2 mg/dl and 6.6 +/- 7.3% (6.6 +/- 5.9 mg/dl and 6.0 +/-
      6.5%, 8.8 +/- 6.7 mg/dl and 9.1 +/- 9.7%, and 10.1 +/- 7.3 mg/dl and 10.7 +/-
      10.1% in group 1, 2, and 3 respectively, P < .001). The subjects with the
      absolute value of the differences of LDL-C >=10% was 20.2% (17.3%, 31.3%, and
      41.1% in group 1, 2, and 3 respectively, P < .001). In the multiple logistic
      regression analysis, high triglyceride (>=150 mg/dl), low high-density
      lipoprotein cholesterol (HDL-C) (<40 mg/dl), male gender, obesity (body mass
      index >=25 kg/m(2)), DM and taking lipid-lowering drugs were significant
      associated with high LDL-differences (the absolute value of the differences >=10%
      or >=10 mg/dl). CONCLUSION: D-LDL-C was generally higher by 5 mg/dl or 5% than C
      LDL-C. The differences C-LDL-C and D-LDL-C were higher in subjects with DM and on
      lipid-lowering medications. Male gender, high triglyceride, low HDL-C, and
      obesity were also associated with the greater differences between C-LDL-C and D
      LDL-C.

PMID- 22385546
TI  - Lipid levels in obese and nonobese subjects as predictors of fasting and postload
      glucose metabolism.
AB  - BACKGROUND: Dyslipidemia in the overweight/obese patient often is associated with
      impaired glucose metabolism. The authors of large clinical trials in different
      ethnic groups highlighted the correlation between glycemia and lipid profile,
      although the effect of abdominal adiposity was not explored. OBJECTIVE: To
      evaluate the relationship of visceral adiposity and lipid profile with fasting
      (FPG) and postload glucose (2hPG) in subjects without known diabetes (DM2).
      METHODS: A total of 3030 subjects were divided in three groups: obese subjects
      (OB; n = 490), nonobese subjects with an increased waist circumference (NOB/W+; n
      = 500), and nonobese subjects without an increased waist circumference (NOB/W-; n
      = 2040). We performed a linear regression analysis among lipid fractions and
      fasting and 2hPG in the three groups, with or without diagnosis of DM2 after
      2hPG. RESULTS: Our data confirmed the significant association (P < .01) of high
      triglycerides and low high-density lipoprotein cholesterol (HDL-C) with fasting
      and 2hPG in all three groups such as for non-HDL cholesterol, whereas total
      cholesterol (TC) showed a significant correlation only with fasting glucose in OB
      and NOB/W+ subjects (P < .01). The analysis with or without DM2 demonstrated no
      difference in the statistical significance, although a better correlation in
      subjects without DM2 was observed. In addition, for each quartile of TC a
      significant trend (P < .01) in prevalence of fasting hyperglycemia in obese and
      in NOB/W+ patients was observed. CONCLUSION: This study suggests that
      triglycerides and HDL-C, together with non-HDL cholesterol, are associated with
      impaired fasting and 2hPG and that high total cholesterol levels are associated
      with abnormalities of fasting glucose metabolism only in patients with elevated
      waist circumference.

PMID- 22385547
TI  - Pregnancy during adolescence has lasting adverse effects on blood lipids: a 10
      year longitudinal study of black and white females.
AB  - BACKGROUND: Primiparity has been associated with 3 to 4 mg/dL lower high-density
      lipoprotein cholesterol concentrations in black and white adult women that
      persist several years after delivery. OBJECTIVE: To examine the lasting effects
      of adolescent pregnancy on blood lipids, an early risk factor for future
      cardiometabolic diseases. DESIGN: The National Heart Lung and Blood Institute's
      Growth and Health Study is a multicenter prospective cohort that measured fasting
      blood lipids for 1013 (513 black, 500 white) participants at baseline (1987-1988)
      ages 9-10, and again at follow-up (1996-1997) ages 18-19. METHODS: Change in
      fasting plasma total cholesterol, triglycerides, low-density lipoprotein
      cholesterol, and high-density lipoprotein cholesterol, defined as the difference
      between baseline and follow-up measurements, was compared among 186 (145 black,
      41 white) primi- or multiparas, 106 (55 black, 51 white) nulliparous, gravidas
      versus 721 (313 black, 408 white) nulligravidas. Fully adjusted multiple linear
      regression models estimated blood lipid changes among these pregnancy groups
      adjusted for race, age at menarche, baseline lipids, physical inactivity, body
      mass index, and family sociodemographics. RESULTS: In the 10-year study period,
      adolescent paras compared with nulligravidas had greater decrements in high
      density lipoprotein cholesterol (mg/dL; fully adjusted mean [95% confidence
      interval] group differences in black -4.3 [-6.7, -2.0]; P < .001 and white: -4.5
      [-8.2, -0.7]; P = .016) and greater increments in fasting triglycerides (mg/dL;
      adjusted mean [95% confidence interval] group differences in black: 10.4 [3.9,
      16.8]; P < .001, and white: 11.6 [-3.6, 26.8]; P = .167). CONCLUSION: Adolescent
      pregnancy contributes to pro-atherogenic lipid profiles that persist after
      delivery. Further research is needed to assess whether adolescent pregnancy has
      implications for future cardiovascular disease risk in young women.

PMID- 22385548
TI  - A multicenter study of nutraceutical drinks for cholesterol (evaluating
      effectiveness and tolerability).
AB  - BACKGROUND: We hypothesized that a nutraceutical formulation containing small
      amounts of bioactive constituents that exert cholesterol-lowering effects by
      different mechanisms may exhibit synergistic efficacy with a clean tolerability
      profile. The purpose of this study was to evaluate nutraceutical fruit-flavored
      drinks with and without red yeast rice (RYR) for effects on low-density
      lipoprotein (LDL) and total cholesterol. METHODS: In double-blinded fashion, 79
      subjects were randomized to one of three fruit-flavored drinks, ie, a placebo,
      and two active drinks containing niacin, phytosterol esters, L-carnitine, vitamin
      C, and Co-Q-10, one with and without RYR, twice daily. Primary end points were
      LDL and total cholesterol percent reductions from baseline. Secondary end points
      were high-density lipoprotein and C-reactive protein percent change from
      baseline. Physician contact and laboratory work were obtained at baseline, 4
      weeks, and 8 weeks of subject participation. RESULTS: A total of 59 subjects
      completed the study. The placebo group and the group receiving the nutraceuticals
      without RYR showed no change in primary or secondary end points. The
      nutraceutical drink with RYR reduced total cholesterol at week 4 by 13% (-35
      mg/dL) and week 8 by 14% (-46 mg/dL). LDL cholesterol decreased 17.1% at 4 weeks
      (-28 mg/dL) and 17.8% at week 8 (-30 mg/dL). In the effective drink arm
      containing nutraceuticals and RYR there were no biochemical or subjective
      intolerance, with the exception of one subject who experienced headache.
      CONCLUSIONS: A nutraceutical drink with RYR can be a safe and effective natural
      alternative to pharmacologic therapies for people intolerant to or refusing
      statins but still in need of achieving and maintaining a healthy and low
      cholesterol level.

PMID- 22385549
TI  - Relationship between serum uric acid and metabolic syndrome: an analysis by
      structural equation modeling.
AB  - OBJECTIVE: To investigate the nature of the relationships between uric acid and
      metabolic syndrome (MetS) components. METHODS: Body mass index, waist
      circumference, serum uric acid, fasting glucose, lipid profiles, and blood
      pressure were measured in 13,811 subjects aged between 18 and 85 years of age.
      Two structural equation models (SEMs) were used to test a hypothesis regarding
      the linking roles of uric acid in the occurrence of MetS components in male and
      female separately. RESULTS: The findings of the SEM demonstrated that increased
      uric acid level was associated with fasting glucose (beta = 0.221, P < .001),
      blood pressure (beta = 0.158, P < .001), and lipid profiles (beta = 0.391, P <
      .001) in women. Increased uric acid level was associated with decreased fasting
      glucose (beta = -0.071, P < .001) and increased lipid profiles (beta = 0.352, P <
      .001) in men. The association was stronger between uric acid and lipid profiles
      than those between uric acid and other MetS components. CONCLUSION: By using SEM,
      we were able to confirm the intimate relationships between uric acid and MetS
      components, particularly in women. The associations between uric acid and MetS
      components were gender specific, and the nature of such association requires
      further exploration.

PMID- 22385550
TI  - Elevation of fasting morning glucose relative to hemoglobin A1c in normoglycemic
      patients treated with niacin and with statins.
AB  - BACKGROUND: Niacin increases fasting glucose levels, and statins modestly
      increase the rate of new-onset diabetes. The clinical importance and mechanisms
      of these effects are not fully explored. OBJECTIVE: On the basis of anecdotal
      observations, we hypothesized that elevated morning fasting glucose may be
      accompanied by relatively normal hemoglobin A1c (HbA1c) in patients treated with
      niacin and other lipid-modifying drugs. We conducted a retrospective cohort
      analysis to test this hypothesis. METHODS: The Duke Lipid Clinic database (1994
      2007) was screened for simultaneous determinations of fasting morning glucose and
      HbA1c, yielding 1483 data pairs among 554 subjects. Subjects with diabetes, by
      clinical diagnosis, medication, or any HbA1c >=6.5%, or nondiabetes were analyzed
      separately. Repeated-measures linear regression featured glucose as dependent
      variable and included terms for HbA1c, drug(s), and their interaction. RESULTS:
      Regression lines for glucose on HbA1c had altered slopes in the presence of
      niacin and/or statin use in normoglycemic subjects. The corresponding interaction
      terms (drug and HbA1c) were significant (niacin P = .026, statin P = .013).
      Fibrate use had no effect (interaction P = .49). When modeled together, niacin
      and statin effects were independent. Regression curves in diabetic patients were
      not affected by lipid medications. CONCLUSION: Elevated fasting glucose may be
      accompanied by relatively normal HbA1c in niacin- and statin-treated patients.
      HbA1c reflects average daily glucose levels and is likely a better measure of the
      glycemic effect of lipid medications. Because our data were retrospective,
      confirmation from randomized trials is needed.

PMID- 22385551
TI  - The relationship between subclinical atherosclerosis, non-high-density
      lipoprotein cholesterol, exercise, and diet among male participants of the PACC
      Project.
AB  - BACKGROUND: Non-high-density lipoprotein (HDL) cholesterol is recommended as a
      secondary lipid goal treated initially with lifestyle modification. However, the
      relationship between non-HDL and subclinical atherosclerosis is unknown. We
      examined the independent relationships between coronary artery calcium (CAC),
      lipids including non-HDL, exercise, and diet among healthy male participants of
      the Prospective Army Coronary Calcium (PACC) Project. METHODS: Male participants
      from the PACC Project (n = 1637, mean age 42.8 years; no history of coronary
      heart disease) were studied. We used validated surveys to measure dietary quality
      and habitual physical exercise. Fasting lipid concentrations and other
      cardiovascular risk variables were measured. Subclinical atherosclerosis was
      detected with the use of electron beam computed tomography for CAC. Factors
      independently associated with the presence of any detectable CAC (CAC score > 0),
      including standard CV risk variables, non-HDL, exercise, and diet, were evaluated
      with the use of logistic regression. RESULTS: The mean Framingham risk score was
      4.6 +/- 2.6%; CAC was present in 22.4%. Fasting lipid concentrations showed mean
      LDL-C 128 +/- 32 mg/dL, HDL-C 50 +/- 13 mg/dL, TG-C 130 +/- 86 mg/dL, and non-HDL
      C 154 +/- 37 mg/dL. Men with CAC had significantly greater levels of LDL-C (135
      vs 127 mg/dL), TG (148 vs 124 mg/dL), and non-HDL-C (164 vs 151 mg/dL) and less
      habitual physical activity (P = 0.006). There were nonsignificant trends between
      prevalent CAC, greater amounts of dietary fat intake, and lower HDL-C. In
      successive multivariable logistic regression models for the dependent variable
      CAC, only non-HDL-C (odds ratio [OR] 1.012 per mg/dL; 95% CI 1.002-1.023; P =
      .019) and age (OR 1.119 per year; 95% CI 1.063-1.178; P < .001) were
      independently associated with the presence of CAC, and exercise (OR 0.808; 95% CI
      0.703-0.928; P = 0.003) was associated with the absence of CAC. CONCLUSIONS: Non
      HDL-C and exercise are independently predictive of the presence of subclinical
      CAC among healthy lower-risk middle-aged men.

PMID- 22385552
TI  - Changes in prescription patterns before and after reporting of the Ezetimibe and
      Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial
      (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol
      reduction.
AB  - BACKGROUND: Recent trends suggest a decreased use of ezetimibe/simvastatin
      combination and coadministered ezetimibe plus statin therapies. OBJECTIVE: This
      analysis evaluated changes in prescription patterns for ezetimibe/simvastatin,
      ezetimibe plus statins, and statin therapies and expected effects on low-density
      lipoprotein cholesterol (LDL-C) lowering during 2007 to 2008. METHODS:
      Prescription pattern changes were assessed by the use of patient-level data from
      the IMS Health Longitudinal Rx database during two time periods, July 14, 2007 to
      January 13, 2008 (n = 8,813,674) and January 14, 2008 to July 13, 2008 (n =
      9,131,030), 6 months before and after reporting of the results of The Ezetimibe
      and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial
      (ENHANCE) trial on January 14, 2008. Expected LDL-C reductions were estimated
      using data from previous controlled clinical trials. RESULTS: During 6 months
      post-ENHANCE, greater proportions of patients were switched from
      ezetimibe/simvastatin and ezetimibe plus statins to other lipid-lowering
      therapies by health care providers than 6 months pre-ENHANCE (21.1% vs 6.0% and
      46.9% vs 38.5%, differences: -15.06% [95% confidence interval -15.14%, -14.97%]
      and -8.43% [95% confidence interval -8.70%, -8.17%], respectively). Greater
      proportions of these patients switched to statin monotherapy in the later than
      earlier period. Prescription patterns were similar for statins during both time
      periods, although fewer patients switched to ezetimibe/simvastatin and ezetimibe
      plus statin therapies post-ENHANCE. In both time periods, greater proportions of
      patients on ezetimibe/simvastatin and ezetimibe plus statins switched to less
      than-equivalent LDL-C lowering efficacy doses of statins than those on statin
      therapy. On the basis of previous clinical data for these therapies, smaller LDL
      C reductions would be expected in patients who switched from
      ezetimibe/simvastatin and ezetimibe plus statins to statins, despite a trend
      toward switching to greater statin doses in the later time period. CONCLUSIONS:
      More patients switched from ezetimibe/simvastatin and ezetimibe plus statin to
      statin monotherapy 6 months after the reporting of the ENHANCE trial, the
      majority of which were prescribed less potent, LDL-C-lowering therapies. On the
      basis of the known LDL-C lowering efficacies for these therapies, such changes
      would be expected to increase LDL-C levels in these patients and may reduce the
      proportion of patients who achieve guideline-recommended LDL-C goals.

PMID- 22385553
TI  - Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels
      and in improving symptoms in a patient with refractory angina secondary to
      accelerated coronary artery disease.
AB  - Coronary artery disease remains a significant cause of morbidity and mortality in
      the Western world. High plasma Lp(a) concentrations are related to the risk of
      cardiovascular disease, but Lp(a) is rarely assayed and treated. We present the
      case of a 50-year-old gentleman with refractory angina, whose coronary disease
      continued to progress despite optimal medical and surgical therapy. We show that
      the aggressive reduction of Lp(a) successfully ameliorated the progression of
      coronary stenosis and provides effective and durable relief of symptoms.

PMID- 22385554
TI  - The effect of a complementary e-learning course on implementation of a quality
      improvement project regarding care for elderly patients: a stepped wedge trial.
AB  - BACKGROUND: Delirium occurs frequently in elderly hospitalised patients and is
      associated with higher mortality, increased length of hospital stay, functional
      decline, and admission to long-term care. Healthcare professionals frequently do
      not recognise delirium, indicating that education can play an important role in
      improving delirium care for hospitalised elderly. Previous studies have indicated
      that e-learning can provide an effective way of educating healthcare
      professionals and improving quality of care, though results are inconsistent.
      METHODS AND DESIGN: This stepped wedge cluster randomised trial will assess the
      effects of a complementary delirium e-learning course on the implementation of
      quality improvement initiative, which aims to enhance the recognition and
      management of delirium in elderly patients. The trial will be conducted in 18
      Dutch hospitals and last 11 months. Measurements will be taken in all
      participating wards using monthly record reviews, in order to monitor delivered
      care. These measurements will include the percentage of elderly patients who were
      screened for the risk of developing delirium, use of the Delirium Observation
      Screening scale, use of nursing or medical interventions, and the percentage of
      elderly patients who were diagnosed with delirium. Data regarding the e-learning
      course will be gathered as well. These data will include user characteristics,
      information regarding use of the course, delirium knowledge before and after
      using the course, and the attitude and intentions of nurses concerning delirium
      care. SETTING: The study will be conducted in internal medicine and surgical
      wards of eighteen hospitals that are at the beginning stages of implementing the
      Frail Elderly Project in the Netherlands. DISCUSSION: Better recognition of
      elderly patients at risk for delirium and subsequent care is expected from the
      introduction of an e-learning course for nurses that is complementary to an
      existing quality improvement project. This trial has the potential to demonstrate
      that e-learning can be a vital part of the implementation process, especially for
      quality improvement projects aimed at complex health issues such as delirium. The
      study will contribute to a growing body of knowledge concerning e-learning and
      the effects it can have on knowledge as well as delivered care. TRIAL
      REGISTRATION: Netherlands Trial Register (NTR): NTR2885.

PMID- 22385556
TI  - Overexpression of Arabidopsis and rice stress genes' inducible transcription
      factor confers drought and salinity tolerance to rice.
AB  - Rice yield is greatly affected by environmental stresses such as drought and
      salinity. In response to the challenge of producing rice plants tolerant to these
      stresses, we introduced cDNA encoding the transcription factors DREB1A and DREB1B
      under the control of the stress inducible rd29 promoter. Two different indica
      rice cultivars were used, BR29, an improved commercially cultivated variety from
      Bangladesh and IR68899B, an IRRI bred maintainer line for hybrid rice.
      Agrobacterium mediated transformation of BR29 was done independently with DREB1A
      isolated from rice and Arabidopsis and DREB1B isolated from rice, whereas
      biolistic transformation was done with rice- DREB1B in the case of IR68899B.
      Initial genetic integration was confirmed by PCR and Southern blot analysis.
      Salinity tolerance was assayed in very young seedlings. Drought stress tests were
      found to be more reliable when they were carried out at the pre-flowering booting
      stage. RNA gel blot analysis as well as quantitative PCR analysis was performed
      to estimate the transcription level under stressed and unstressed conditions.
      Agronomic performance studies were done with stressed and unstressed plants to
      compare the yield losses due to dehydration and salt loading stresses. Noticeably
      enhanced tolerance to dehydration was observed in the plants transformed with
      DREB1A isolated from Arabidopsis while DREB1B was found to be more effective for
      salt tolerance.

PMID- 22385555
TI  - Dunno if you've any plans for the future: medical student indirect questioning in
      simulated oncology interviews.
AB  - BACKGROUND: This exploratory study investigated the motives of medical students
      (N = 63) for using indirect questions of the type I don't know if [you have
      already heard about chemotherapies], I don't know how [you are], or I don't know
      what [you do for a living] in simulated patient interviews during a communication
      skills course. METHODS: I don't know questions (IDK-Qs) were observed during the
      initial evaluation of students' communication skills; they were systematically
      identified through video screening and subjected to a qualitative content and
      discourse analysis considering their context, their content, their intent and
      their effect on the simulated patients. To evaluate the specificity of medical
      students' IDK-Qs, the data were compared with a data set of oncologists (N = 31)
      conducting simulated patient interviews in the context of a Communication Skills
      Training (CST). RESULTS: During the interviews, 41.3% of the students asked 1-6
      IDK-Qs. The IDK-Qs were attributed to three content categories: medical/treatment
      questions (N = 24); lifestyle/psychosocial questions (N = 18); and "inviting
      questions" questions (N = 11). Most of the IDK-Qs had an exploratory function
      (46/53), with simulated patients providing detailed responses or asking for more
      information (36/53). IDK-Qs were rare in the oncologist sample compared to the
      student sample (5 vs. 53 occurrences). CONCLUSIONS: IDK-Qs showed a question
      design difference between medical students and oncologists in simulated patient
      interviews. Among other reasons for this difference, the possible function of IDK
      Qs as a protective linguistic strategy and marker for psychological discomfort is
      discussed.

PMID- 22385557
TI  - Cyanido-bridged Fe(III)-Mn(III) heterobimetallic materials built from Mn(III)
      Schiff base complexes and di- or tri-cyanido Fe(III) precursors.
AB  - The reaction of [Fe(III)L(CN)(3)](-) (L being bpca = bis(2
      pyridylcarbonyl)amidate, pcq = 8-(pyridine-2-carboxamido)quinoline) or
      [Fe(III)(bpb)(CN)(2)](-) (bpb = 1,2-bis(pyridine-2-carboxamido)benzenate) ferric
      complexes with Mn(III) salen type complexes afforded seven new bimetallic cyanido
      bridged Mn(III)-Fe(III) systems: [Fe(pcq)(CN)(3)Mn(saltmen)(CH(3)OH)].CH(3)OH
      (1), [Fe(bpca)(CN)(3)Mn(3-MeO-salen)(OH(2))].CH(3)OH.H(2)O (2),
      [Fe(bpca)(CN)(3)Mn(salpen)] (3), [Fe(bpca)(CN)(3)Mn(saltmen)] (4),
      [Fe(bpca)(CN)(3)Mn(5-Me-saltmen)].2CHCl(3) (5), [Fe(pcq)(CN)(3)Mn(5-Me
      saltmen)].2CH(3)OH.0.75H(2)O (6), and [Fe(bpb)(CN)(2)Mn(saltmen)].2CH(3)OH (7)
      (with saltmen(2-) = N,N'-(1,1,2,2-tetramethylethylene)bis(salicylideneiminato)
      dianion, salpen(2-) = N,N'-propylenebis(salicylideneiminato) dianion, salen(2-) =
      N,N'-ethylenebis(salicylideneiminato) dianion). Single crystal X-ray diffraction
      studies were carried out for all these compounds indicating that compounds 1 and
      2 are discrete dinuclear [Fe(III)-CN-Mn(III)] complexes while systems 3-7 are
      heterometallic chains with {-NC-Fe(III)-CN-Mn(III)} repeating units. These chains
      are connected through pi-pi and short contact interactions to form extended
      supramolecular networks. Investigation of the magnetic properties revealed the
      occurrence of antiferromagnetic Mn(III)...Fe(III) interactions in 1-4 while
      ferromagnetic Mn(III)...Fe(III) interactions were detected in 5-7. The nature of
      these Mn(III)...Fe(III) magnetic interactions mediated by a CN bridge appeared to
      be dependent on the Schiff base substituent. The packing is also strongly
      affected by the nature of the substituent and the presence of solvent molecules,
      resulting in additional antiferromagnetic interdinuclear/interchain interactions.
      Thus the crystal packing and the supramolecular interactions induce different
      magnetic properties for these systems. The dinuclear complexes 1 and 2, which
      possess a paramagnetic S(T) = 3/2 ground state, interact antiferromagnetically in
      their crystal packing. At high temperature, the complexes 3-7 exhibit a one
      dimensional magnetic behavior, but at low temperature their magnetic properties
      are modulated by the supramolecular arrangement: a three-dimensional
      antiferromagnetic order with a metamagnetic behavior is observed for 3, 4, and 7,
      and Single-Chain Magnet properties are detected for 5 and 6.

PMID- 22385559
TI  - The next decade: how it might unfold.

PMID- 22385560
TI  - Integrative medicine in 2021: an imagined retrospective.

PMID- 22385558
TI  - Left atrial primary B cell lymphoma presenting with mitral regurgitation.
AB  - Primary cardiac lymphoma (PCL) is an extremely rare diagnosis. We present a case
      of a 38-year-old immunocompetent female who presented with dyspnea on exertion
      and chest pain and the echocardiography revealed a mass in the left atrium (LA)
      causing moderate mitral regurgitation and mimicking a left atrial myxoma. The
      patient was managed with excision of the mass and mitral valve replacement
      followed by chemotherapy. The histopathology revealed B-cell non-Hodgkin lymphoma
      (NHL) with tumor cells showing immunoreactivity with CD20 and negative for
      CD45RO.

PMID- 22385561
TI  - Survey of integrative medicine centers released.

PMID- 22385562
TI  - Social values, social wellness: can we know what works?

PMID- 22385563
TI  - A mind-body technique for symptoms related to fibromyalgia and chronic fatigue.
AB  - CONTEXT: A novel mind-body approach (amygdala retraining) is hypothesized to
      improve symptoms related to fibromyalgia and chronic fatigue. OBJECTIVE: To
      examine the use of a mind-body approach for improving symptoms related to
      fibromyalgia and chronic fatigue. DESIGN: This was a single-blind, randomized
      controlled trial. SETTING: The study was conducted in a tertiary-care
      fibromyalgia and chronic fatigue clinic. PATIENTS: Patients with fibromyalgia,
      chronic fatigue, or both were included. INTERVENTIONS: Patients were randomly
      assigned to receive amygdala retraining along with standard care or standard care
      alone. Standard care involved attending a 1.5-day multidisciplinary program. The
      amygdala retraining group received an additional 2.5-hour training course in
      which the key tools and techniques adapted from an existing program were taught
      to the patient. A home-study video course and associated text were provided to
      supplement the on-site program. Both groups received telephone calls twice a
      month to answer questions related to technique and to provide support. MAIN
      OUTCOME MEASURES: Validated self-report questionnaires related to general health,
      well-being, and symptoms, including Short Form-36, Measure Yourself Medical
      Outcome Profile, Multidimensional Fatigue Inventory, Epworth Sleepiness Scale,
      and Fibromyalgia Impact Questionnaire. RESULTS: Of the 44 patients randomly
      assigned who completed baseline assessments, 21 patients completed the study (14
      in the standard care group and 7 in the study group). Median age was 48 years
      (range, 27-56 years), and female subjects comprised 91% of the group. Analyses
      demonstrated statistically significant improvements in scores for physical
      health, energy, pain, symptom distress, and fatigue in patients who received the
      amygdala retraining compared with standard care.

PMID- 22385564
TI  - Acupuncture and heart rate variability: a systems level approach to understanding
      mechanism.
AB  - Recent research has elucidated several different mechanisms for acupuncture.
      However, the interrelationship between these mechanisms and how acupuncture
      affects complex physiological systems is still not understood. Heart rate
      Variability (HRV), the beat-to-beat fluctuations in the rhythm of the heart,
      results from the regulation of the heart by the autonomic nervous system (ANS).
      Low HRV is associated with increased risk of all-cause mortality and is a marker
      for a wide range of diseases. Coherent HRV patterns are associated with increased
      synchronization between the two branches of the ANS, and when sustained for long
      periods of time result in increased synchronization and entrainment between
      multiple body systems. There is strong evidence from randomized placebo
      controlled trials that acupuncture modulates HRV. This may represent a
      mechanistic pathway for global physiological regulation, which is congruent with
      East Asian medical theory. The ability of acupuncture to improve HRV could be
      used as a tool in acupuncture research and practice to monitor treatment
      effectiveness and the impact on quality of life.

PMID- 22385565
TI  - Randomized expectancy-enhanced placebo-controlled trial of the impact of Quantum
      BioEnergetic distant healing and paranormal belief on mood disturbance: a pilot
      study.
AB  - CONTEXT: Previous research has demonstrated the effects of ostensible subtle
      energy on physical systems and subjective experience. However, one subtle energy
      technique that has been neglected, despite anecdotal support for its efficacy, is
      Quantum BioEnergetics (QBE). Furthermore, the influence of paranormal belief and
      experience (either real belief/experience or suggested belief/experience) on
      subtle energy effects remains unclear. OBJECTIVE: The aim of the present study
      was to investigate experimentally the effects of distant QBE healing, and
      paranormal belief/experience, on mood. DESIGN: A randomized expectancy-enhanced
      placebo-controlled design was used. SETTING: Data were collected at the QBE
      Centre, Melbourne. PARTICIPANTS: Participants were students from Deakin
      University and from the general public. METHODS: Snowball sampling (ie, word-of
      mouth) and convenience sampling using a ballot box placed in the university
      library. OUTCOME MEASURES: Profile of Mood States-Short Form was used to quantify
      positive and negative mood states. RESULTS: The QBE condition was associated with
      (1) significantly less Tension-Anxiety compared with the placebo and control
      condition; and (2) significantly less Anger-Hostility and Total Mood Disturbance
      compared with the control condition (but not the placebo condition). Furthermore,
      there was an interaction of condition and paranormal belief/experience with
      regard to Depression-Dejection, with believers assigned to the placebo condition
      scoring lowest on this Mood variable. CONCLUSION: Findings suggest that the use
      of QBE by an experienced practitioner reduces mood disturbance. In addition, the
      placebo condition may have evoked suggestibility effects in believers, which
      would mean that they may be more likely than nonbelievers to believe that they
      were receiving healing, thus resulting in lower Depression-Dejection scores.

PMID- 22385567
TI  - Longitudinal impact of yoga on chemotherapy-related cognitive impairment and
      quality of life in women with early stage breast cancer: a case series.
AB  - PURPOSE: Adjuvant chemotherapy for women with breast cancer has significantly
      improved the cure rate; however, it has been associated with chemotherapy-related
      cognitive impact (CRCI). The literature provides preliminary support for the
      feasibility and efficacy of yoga interventions for the general cancer population,
      however, controlled trials are scarce and no studies have examined the effect of
      yoga on cognition for women with breast cancer during chemotherapy. This case
      series aims to identify the impact of yoga on measures of cognition, functional
      outcomes, and quality of life (QOL) for breast cancer survivors (BCS). METHODS:
      Four women with a diagnosis of early-stage breast cancer prior to chemotherapy
      treatment were administered the following physiologic measures at baseline, 6,
      and 12 weeks during chemotherapy, and at one and three months after the
      conclusion of the study: Functional Reach test (balance) and Sit and Reach test
      (flexibility), and QOL, POMS (Mood) and FACT-B (QOL), at baseline. Primary
      outcomes of cognition were measured with the Perceived Cognition Questionnaire
      (PCQ) and CogState, a computerized measurement of cognition. Women attended an
      Iyengar-inspired yoga program twice a week for 12 weeks. Qualitative
      questionnaires were administered after the completion of the study to determine
      perceived benefits and challenges of the yoga program. RESULTS: Four women with
      Stage II breast cancer ranged in age from 44-65 years. CogState computerized
      testing showed changes in varying domains of cognition through treatment and
      follow-up. Improved balance, flexibility, and QOL were also noted over time. No
      adverse events were observed. Analysis of qualitative data revealed the yoga
      classes were helpful and subjects continued the practice elements of yoga
      including relaxation, breathing, and stretching. The most challenging aspect of
      the study was physical limitations due to various medical complications and
      included fatigue, decreased range of motion, and pain. CONCLUSION: This case
      series suggests that yoga may impact various aspects of cognition during and
      after chemotherapy administration as noted through quantitative measures. Women
      describe yoga as improving various domains of QOL through the treatment
      trajectory. This mind-body intervention may stave off CRCI; however, further
      investigation is needed for additional randomized controlled trials on the
      effects of yoga on cognition for women with breast cancer undergoing adjuvant
      chemotherapy treatment.

PMID- 22385570
TI  - Allosteric regulation: guest editor's introduction.

PMID- 22385569
TI  - Teaching anatomy to chiropractic students: experiences from Macquarie University,
      Sydney.

PMID- 22385566
TI  - How might yoga help depression? A neurobiological perspective.

PMID- 22385571
TI  - Nanowired drug delivery to enhance neuroprotection in spinal cord injury.
AB  - Spinal cord injury (SCI) is a serious clinical situation for which no suitable
      drug therapy exists. SCI often results in paraplegia or quadriplegia and, apart
      from the personal trauma leads to huge costs to society for rehabilitation or day
      to-day life support. Sensory motor dysfunction following SCI is mainly a
      consequence of the slowly progressing cord pathology after primary injury that
      worsens over tine. Thus, almost all sensory and motor nerve control and pathways
      passing through spinal cord and reflexes are compromised in SCI patients. As a
      result their peripheral nervous system, autonomic nervous function and central
      nervous system regulations are adversely affected. Experiments carried out in our
      laboratory show that various therapeutic agents, if given within 10 to 30 minutes
      after primary SCI could correct morphological changes to a certain extent. In
      these rat models of SCI reduction in cord pathology, e.g., bloodspinal cord
      barrier (BSCB) breakdown, edema formation and cell injury by the neuroprotective
      agents that also limited sensory motor dysfunction and improved functional
      behavior. However, these drugs if given beyond 30 minutes after SCI showed a
      markedly reduced neuroprotective efficacy. Thus, new strategies are needed to
      enhance neuroprotection in SCI to prevent structural and functional changes over
      longer periods of time. To that end our laboratory has initiated a series of
      investigations in which nanowired delivery of various neurotherapeutic agents are
      applied after different time periods of SCI, that resulted in a much better
      outcome than with the parent compounds under identical conditions. The superior
      neuroprotective activity of nanowired compound delivery could be due to a reduced
      metabolism of active compounds in the central nervous system (CNS) or by
      sustained release of the drug for longer times. In addition, nanowired drugs may
      penetrate the CNS faster and could reach widespread areas once entering the
      spinal cord. Thus, nanowired drug delivery to treat SCI may have potential
      therapeutic value. These aspects of nanowired drug delivery to enhance
      neuroprotection in SCI are discussed in this review based on our own
      investigations.

PMID- 22385572
TI  - Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic
      cancer.
AB  - INTRODUCTION: To evaluate efficacy and secondary resectability in patients with
      locally advanced pancreatic cancer (LAPC) treated with neoadjuvant
      chemoradiotherapy (CRT). PATIENTS AND METHODS: A total of 215 patients with
      locally advanced pancreatic cancer were treated with chemoradiation at a single
      institution. Radiotherapy was delivered with a median dose of 52.2 Gy in single
      fractions of 1.8 Gy. Chemotherapy was applied concomitantly as gemcitabine (GEM)
      at a dose of 300 mg/m2 weekly, followed by adjuvant cycles of full-dose GEM (1000
      mg/m2). After neoadjuvant CRT restaging was done to evaluate secondary
      resectability. Overall and disease-free survival were calculated and prognostic
      factors were estimated. RESULTS: After CRT a total of 26% of all patients with
      primary unresectable LAPC were chosen to undergo secondary resection. Tumour free
      resection margins could be achieved in 39.2% (R0-resection), R1-resections were
      seen in 41.2%, residual macroscopic tumour in 11.8% (R2) and in 7.8% resection
      were classified as Rx. Patients with complete resection after CRT showed a
      significantly increased median overall survival (OS) with 22.1 compared to 11.9
      months in non-resected patients. Median OS and disease-free survival (DFS) of all
      patients were 12.3 and 8.1 months respectively. In most cases the first site of
      disease progression was systemic with hepatic (52%) and peritoneal (36%)
      metastases. DISCUSSION: A high percentage of patients with locally advanced
      pancreatic cancer can undergo secondary resection after gemcitabine-based
      chemoradiation and has a relative long-term prognosis after complete resection.

PMID- 22385574
TI  - Comparative study on liposome targeting to tumor endothelium.

PMID- 22385573
TI  - Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of
      bone marrow mesenchymal stromal cells.
AB  - INTRODUCTION: The capacity of bone marrow mesenchymal stromal cells (BMSCs) to be
      induced into chondrocytes has drawn much attention for cell-based cartilage
      repair. BMSCs represent a small proportion of cells of the bone marrow stromal
      compartment and, thus, culture expansion is a necessity for therapeutic use.
      However, there is no consensus on how BMSCs should be isolated nor expanded to
      maximize their chondrogenic potential. During embryonic development pluripotent
      stem cells differentiate into chondrocytes and form cartilage in a hypoxic
      microenvironment. METHODS: Freshly harvested human BMSCs were isolated and
      expanded from the aspirates of six donors, under either hypoxic conditions (3%
      O2) or normoxic conditions (21% O2). A colony-forming unit fibroblastic (Cfu-f)
      assay was used to determine the number of cell colonies developed from each
      donor. BMSCs at passage 2 (P2) were characterized by flow cytometry for the
      phenotypic expression of cell surface markers on mesenchymal stem cells. BMSCs at
      P2 were subsequently cultured in vitro as three-dimensional cell pellets in a
      defined serum-free chondrogenic medium under normoxic and hypoxic conditions.
      Chondrogenic differentiation of the BMSCs was characterized by biochemical and
      histological methods and by quantitative gene-expression analysis. RESULTS: After
      14 days of culture, the number of BMSC colonies developed under hypoxia was
      generally higher (8% to 38% depending on donor) than under normoxia. BMSCs were
      positive for the cell surface markers CD13, CD29, CD44, CD73, CD90, CD105 and
      CD151, and negative for CD34. Regardless of the oxygen tension during pellet
      culture, hypoxia-expanded BMSC pellets underwent a more robust chondrogenesis
      than normoxia-expanded BMSC pellets after three weeks of culture, as judged by
      increased glycosaminoglycan synthesis and Safranin O staining, along with
      increased mRNA expression of aggrecan, collagen II and Sox9. Hypoxic conditions
      enhanced the mRNA expression of hypoxia inducible factor-2 alpha (HIF-2alpha) but
      suppressed the mRNA expression of collagen X in BMSC pellet cultures regardless
      of the oxygen tension during BMSC isolation and propagation. CONCLUSIONS: Taken
      together, our data demonstrate that isolation and expansion of BMSCs under
      hypoxic conditions augments the chondrogenic potential of BMSCs. This suggests
      that hypoxia-mediated isolation and expansion of BMSCs may improve clinical
      applications of BMSCs for cartilage repair.

PMID- 22385575
TI  - A novel ENG mutation causing impaired co-translational processing of endoglin
      associated with hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant
      vascular dysplasia caused by mutations in mainly the endoglin gene (ENG) or
      activin-like kinase receptor 1 (ALK1) gene (ACVRL1). We investigated the
      molecular basis of HHT in a Japanese patient, and identified a novel missense
      mutation in ENG (c.38T>A, p.Leu13Gln) located in the signal peptide's hydrophobic
      core, but not in ACVRL1. In experiments in COS-1 cells, the Leu13Gln (L13Q)
      mutant endoglin appeared to be expressed as a precursor form, probably due to
      impaired protein processing. Flow cytometry analyses of the COS-1 cells
      transiently expressing recombinant endoglins revealed that the wild-type endoglin
      was detected on the cell surface, but the L13Q mutant was not. We also analyzed
      expression patterns of the recombinant endoglins by immunofluorescent staining,
      and found that the wild-type co-localized with the endoplasmic reticulum (ER),
      but the L13Q mutant did not. These results implied that the L13Q mutant endoglin
      fails to insert into the ER, probably due to destruction of the hydrophobic core
      structure in the signal peptide to be recognized by signal recognition particles.
      Thus, the Leu13 in the signal peptide of endoglin might be essential for correct
      protein processing through the ER and cell-surface expression. Taken together,
      the novel c.38T>A mutation in ENG would impair co-translational processing of the
      endoglin, and could be responsible for HHT in this patient.

PMID- 22385576
TI  - Mechanistic roles for calcium and vitamin D in the regulation of body weight.
AB  - Low intakes of calcium and inadequate vitamin D status often cluster with higher
      prevalence rates of obesity. Consequently, there has been much interest in the
      mechanisms by which calcium and vitamin D could regulate body weight and
      adiposity. This review has focused on randomized controlled trials (RCTs) that
      have manipulated these nutrients and studied pathways of energy balance. Overall,
      there is consistent evidence that calcium and vitamin D increase whole body fat
      oxidation after single and multiple meals, and that calcium promotes a modest
      energy loss through increased faecal fat excretion. The evidence is equivocal for
      a greater diet-induced thermogenesis, increased lipolysis, suppression of key
      lipogenic enzymes, decreased hunger ratings or reduced energy/macronutrient
      intake. Emerging evidence suggests a potential improvement in insulin sensitivity
      following vitamin D that would impinge on food intake and substrate oxidation.
      However, the very few RCTs on supplemental vitamin D and energy balance have not
      explored postprandial avenues of the hormone's actions. Future efforts in this
      area need to define the threshold intake of these nutrients that would maximize
      metabolic and gastrointestinal outcomes. Such studies would provide a platform
      for endorsing the non-skeletal role of calcium and vitamin D in human
      pathophysiology.

PMID- 22385577
TI  - A retrospective analysis of amputation rates in diabetic patients: can lower
      extremity amputations be further prevented?
AB  - BACKGROUND: Lower extremity amputations are costly and debilitating complications
      in patients with diabetes mellitus (DM). Our aim was to investigate changes in
      the amputation rate in patients with DM at the Karolinska University Hospital in
      Solna (KS) following the introduction of consensus guidelines for treatment and
      prevention of diabetic foot complications, and to identify risk groups of lower
      extremity amputations that should be targeted for preventive treatment. METHODS:
      150 diabetic and 191 nondiabetic patients were amputated at KS between 2000 and
      2006; of these 102 diabetic and 99 nondiabetic patients belonged to the catchment
      area of KS. 21 diabetic patients who belonged to KS catchment area were amputated
      at Danderyd University Hospital. All patients' case reports were searched for
      diagnoses of diabetes, vascular disorders, kidney disorders, and ulcer infections
      of the foot. RESULTS: There was a 60% reduction in the rate of amputations
      performed above the ankle in patients with DM during the study period. Patients
      with DM who underwent amputations were more commonly affected by foot infections
      and kidney disorders compared to the nondiabetic control group. Women with DM
      were 10 years older than the men when amputated, whereas men with DM underwent
      more multiple amputations and had more foot infections compared to the women. 88%
      of all diabetes-related amputations were preceded by foot ulcers. Only 30% of the
      patients had been referred to the multidisciplinary foot team prior to the
      decision of amputation. CONCLUSIONS: These findings indicate a reduced rate of
      major amputations in diabetic patients, which suggests an implementation of the
      consensus guidelines of foot care. We also propose further reduced amputation
      rates if patients with an increased risk of future amputation (i.e. male sex,
      kidney disease) are identified and offered preventive treatment early.

PMID- 22385578
TI  - Robot-assisted pancreatoduodenectomy with preservation of the vascular supply for
      autologous islet cell isolation and transplantation: a case report.
AB  - INTRODUCTION: For patients with chronic pancreatitis presenting with medically
      intractable abdominal pain, surgical intervention may be the only treatment
      option. However, extensive pancreatic resections are typically performed open and
      are associated with a substantial amount of postoperative pain, wound
      complications and long recovery time. Minimally invasive surgery offers an avenue
      to improve results; however, current limitations of laparoscopic surgery render
      its application in the setting of chronic pancreatitis technically demanding.
      Additionally, pancreatic resections are associated with a high incidence of
      diabetes. Transplantation of islets isolated from the resected pancreas portion
      offers a way to prevent post-surgical diabetes; however, preservation of the
      vascular supply during pancreatic resection, which determines islet cell
      viability, is technically difficult using current laparoscopic approaches. With
      recent advances in the surgical field, robotic surgery now provides a means to
      overcome these obstacles to achieve the end goals of pain relief and preserved
      endocrine function. We present the first report of a novel, minimally invasive
      robotic approach for resection of the pancreatic head that preserves vascular
      supply and enables the isolation of a high yield of viable islets for
      transplantation. CASE PRESENTATION: A 35-year old Caucasian woman presented with
      intractable chronic abdominal pain secondary to chronic pancreatitis, with a
      stricture of her main pancreatic duct at the level of the ampulla of Vater and
      distal dilatation. She was offered a robotic-assisted pylorus-preserving
      pancreatoduodenectomy and subsequent islet transplantation, to both provide pain
      relief and preserve insulin-secretory reserves. CONCLUSION: We present a novel,
      minimally invasive robotic approach for resection of the pancreatic head with
      complete preservation of the vascular supply, minimal warm ischemia time (less
      than three minutes) and excellent islet recovery (134,727 islet equivalent). Our
      patient is currently pain-free with normal glycemic control. Robot-assisted
      pylorus-preserving pancreatoduodenectomy and autologous islet transplantation can
      be safely performed and has the potential to minimize operative traumas as well
      as to partially preserve endocrine function. Results from this case report
      suggest that this dual procedure should be considered as a treatment option for
      patients with chronic pancreatitis at earlier stages of the disease, before
      irreversible islet loss occurs.

PMID- 22385579
TI  - Quantitative polymerase chain reaction using infrared heating on a microfluidic
      chip.
AB  - The IR-mediated polymerase chain reaction (IR-PCR) in microdevices is an
      established technique for rapid amplification of nucleic acids. In this report,
      we have expanded the applicability of the IR-PCR to quantitative determination of
      starting copy number by integrating fluorescence detection during the
      amplification process. Placing the microfluidic device between an IR long-pass
      filter and a hot mirror reduced the background to a level that enabled
      fluorescence measurements to be made throughout the thermal cycling process. The
      average fluorescence intensity during the extension step showed the expected
      trend of an exponential increase followed by a plateau phase in successive
      cycles. PUC19 templates at different starting copy numbers were amplified, and
      the threshold cycle showed an increase for decreasing amounts of starting DNA.
      The amplification efficiency was 80%, and the gel separation indicated no
      detectable nonspecific product. A melting curve was generated using IR heating,
      and this indicated a melting temperature of 85  degrees C for the 304 bp
      amplicon, which compared well to the melting temperature obtained using a
      conventional PCR system. This methodology will be applicable in other types of IR
      mediated amplification systems, such as isothermal amplification, and in highly
      integrated systems that combine pre- and post-PCR processes.

PMID- 22385580
TI  - Localization of natriuretic peptides in the cardiac pacemaker of Atlantic salmon
      (Salmo salar L.).
AB  - This study describes the location of the primary pacemaker at the sino-atrial
      (SA) junction and the localization of salmon cardiac peptide (sCP) and
      ventricular natriuretic peptide (VNP) in Atlantic salmon (Salmo salar L.). The
      pacemaker tissue appeared lightly stained and composed of: (1) wavy nerve bundles
      with oval elongated wavy appearing nuclei with pointed ends, (2) ganglion cells
      (12-22 MUm) with granular cytoplasm and (3) wide muscle fibers with large nuclei
      (modified cardiomyocytes) clearly distinguishing them from the other myocardial
      cells. Pacemaker tissue was further evaluated using immunohistochemical staining.
      Immunoreactivity of natriuretic peptides (sCP and VNP) antisera showed specific
      staining in pacemaker ganglion cells in addition to the cardiomyocytes. Positive
      staining with anti-CD3E antisera in the pacemaker ganglion cells is a novel
      finding in teleosts and is consistent with observations in mammals. In
      conclusion, the Atlantic salmon pacemaker was shown to be located at the SA node
      and to harbor sCP and VNP peptides, suggesting a possible neuromodulatory and/or
      neurotransmitter role for these cardiac hormones within the teleost heart.

PMID- 22385581
TI  - [Right hydropneumothorax due to enteral feeding. Nasogastric tube inside airway].

PMID- 22385582
TI  - [Primary cardiac tumours: clinical presentation and prognosis in the elderly].

PMID- 22385583
TI  - [Influence of dementia in functional recovery of hip fracture in elderly
      population].

PMID- 22385584
TI  - [Importance of neuroimaging in the diagnoses of Creutzfeldt-Jakob disease].

PMID- 22385585
TI  - [Neutrophilic dermatosis of the hands].

PMID- 22385586
TI  - [Effectiveness of an educational intervention on hypertension directed at elderly
      hypertensive patients].
AB  - INTRODUCTION: Hypertension is the most prevalent cardiovascular risk factor among
      people over the age 60. The aim of this study is to assess the effectiveness of
      an educational intervention tool, and its reliability. MATERIAL AND METHODS:
      Experimental study, prospective, randomised, parallel-group in a sample of 120
      patients, 62 in the intervention group and 58 in the control group. The
      intervention group received a written and oral educational program on
      hypertension and cardiovascular risk; the control group did not receive any
      intervention. RESULTS: At the end of the intervention there was an increase in
      the percentage of correct responses, with statistically significant differences
      compared to the control group, as regards knowledge of hypertension, risk factors
      associated with the risks of having high blood pressure and control medication.
      CONCLUSION: The implementation of an educational intervention on hypertension and
      cardiovascular risk associated with the same care activity is capable of
      increasing the level of knowledge by elderly hypertensive patients admitted to
      hospital.

PMID- 22385587
TI  - [Results of integrating pharmaceutical care in an Acute Geriatric Unit].
AB  - OBJECTIVE: To evaluate whether the integration of pharmaceutical care in an acute
      geriatric unit can promote the detection of potentially inappropriate drug
      prescriptions (PIP) and adverse drug events (ADE), and if this can improve
      patient and caregiver information at hospital discharge. METHOD: Descriptive
      prospective study in older patients admitted for acute care in the Geriatric
      Department of a university hospital. On admission, a pharmacist recorded a
      comprehensive drug history from the patient, caregiver and other available
      sources, and reviewed preadmission treatments in order to detect adverse drug
      events (using the 3(rd) Granada consensus criteria) and potentially inappropriate
      prescriptions (using STOPP-START criteria). At hospital discharge, the pharmacist
      informed patients and caregivers about the treatment and gave them computer
      generated written information for all drugs prescribed. RESULTS: In a 9 month
      period 189 patients (84.7% of all admissions) were included in the pharmaceutical
      care program (71.9% women, mean age 87.2+/-5.5 years). After analysing 1523
      prescriptions (mean drugs/patient 8.1+/-3.3), 356 (23.4%) potentially
      inappropriate prescriptions and 580 (38.1%) adverse drug events were detected
      (1.9 PIP and 3.2 ADE per patient). Almost three-quarters (74.2%) of the patients
      had at least one PIP: STOPP (48.9%) and START (26.9%). The most frequent adverse
      drug event was an untreated health problem. The pharmacist offered verbal and
      written information to 74.7% of the discharged patients. CONCLUSION: Adding
      pharmaceutical care to the multidisciplinary activity of an acute geriatric care
      unit enables a great number of potentially inappropriate prescriptions and
      adverse drug events to be detected, and increases patient and caregiver
      information at hospital discharge.

PMID- 22385588
TI  - [Systemic lupus erythematosus in the elderly].
AB  - Late-onset systemic lupus erythematosus (SLE) usually appears in patients older
      than 65 years and has clinical features different from the classical form
      observed in younger patients. In the elderly, SLE represents 10-20% of all SLE
      cases, shows a different and less aggressive clinical evolution and the first
      manifestations are non-specific. A significantly higher incidence of late-onset
      SLE in males, and the fact that postmenopausal women have a more benign disease,
      suggests that the estrogenic status may influence the activity of the disease.
      Owing to the insidious onset and the non-specific clinical manifestations on
      presentation, there is commonly a delayed diagnosis of late-onset SLE.
      Furthermore, the presence of comorbidities and concomitant therapies in elderly
      patients may limit the therapeutic options for SLE. The treatment of choice of
      joint symptoms and serositis includes non-steroidal anti-inflammatory drugs and
      low-dose steroids for short periods. In addition to the need for adopting a
      multidisciplinary approach, it is fundamental to obtain information about the
      functional, cognitive and social status of these patients in order to make
      appropriate healthcare decisions.

PMID- 22385589
TI  - European consumers and health claims: attitudes, understanding and purchasing
      behaviour.
AB  - Health claims on food products are often used as a means to highlight
      scientifically proven health benefits associated with consuming those foods. But
      do consumers understand and trust health claims? This paper provides an overview
      of recent research on consumers and health claims including attitudes,
      understanding and purchasing behaviour. A majority of studies investigated
      selective product-claim combinations, with ambiguous findings apart from
      consumers' self-reported generic interest in health claims. There are clear
      indications that consumer responses differ substantially according to the nature
      of carrier product, the type of health claim, functional ingredient used or a
      combination of these components. Health claims tend to be perceived more
      positively when linked to a product with an overall positive health image,
      whereas some studies demonstrate higher perceived credibility of products with
      general health claims (e.g. omega-3 and brain development) compared to disease
      risk reduction claims (e.g. bioactive peptides to reduce risk of heart disease),
      others report the opposite. Inconsistent evidence also exists on the correlation
      between having a positive attitude towards products with health claims and
      purchase intentions. Familiarity with the functional ingredient and/or its
      claimed health effect seems to result in a more favourable evaluation. Better
      nutritional knowledge, however, does not automatically lead to a positive
      attitude towards products carrying health messages. Legislation in the European
      Union requires that the claim is understood by the average consumer. As most
      studies on consumers' understanding of health claims are based on subjective
      understanding, this remains an area for more investigation.

PMID- 22385590
TI  - Radiologic case study. Talar neck fracture with tibiotalar and posterior subtalar
      dislocation.

PMID- 22385591
TI  - Treatment of lateral epicondylitis through digital blunt adhesiolysis.

PMID- 22385592
TI  - Pyogenic cervical spondylitis caused by Pasteurella haemolytica attributed to
      excessive contact with dogs.

PMID- 22385594
TI  - Expandable prostheses for the leg in children.

PMID- 22385595
TI  - Tension suture fixation using 2 washers for proximal humeral fractures.
AB  - The surgical treatment for proximal humeral fractures is challenging, especially
      in patients with osteoporosis. Locking plates and intramedullary nails have been
      widely used with satisfactory results, but previously reported complications have
      not been substantially reduced. Several authors have emphasized the importance of
      maintaining soft tissues around the proximal humerus with respect to limiting
      displacement and maintaining stability. To prevent postoperative complications,
      such as fixation failure and malunion, several supplementary suture techniques
      using nonabsorabable sutures that allow for the incorporation of the rotator cuff
      as a fixation point have been described.

PMID- 22385596
TI  - Musculoskeletal tumors.

PMID- 22385597
TI  - Epidemiology of meniscal injury associated with ACL tears in young athletes.
AB  - The epidemiologic characteristics of concomitant meniscal tears that occur at the
      time of anterior cruciate ligament (ACL) injury have been variably reported. The
      purpose of this study was to assess the epidemiology of meniscal tears that occur
      in the ACL-injured knee of a young, athletic population at a single institution.
      We were unable to find a difference in meniscal tear incidence based on sex,
      mechanism of injury, sport, or time to surgery. In addition, we found that the
      cumulative incidence of isolated medial meniscal tears was significantly higher
      than the cumulative incidence of isolated lateral meniscal tears. Our prospective
      study design and ability to identify and follow all patients in our study
      population make this a unique study.

PMID- 22385598
TI  - Management of postoperative ileus.
AB  - Postoperative ileus, a temporary cessation in bowel motility, is a common and
      significant complication of major surgery. Consequences of postoperative ileus
      include increased patient discomfort, delayed time to adequate nutrition,
      prolonged length of stay, and increased cost to the patient and healthcare
      system. The traditional, multi-modal approach to the resolution of postoperative
      ileus includes opioid minimization, early ambulation, and early feeding. Newer
      medications, such as methlynaltrexone and alvimopan (which are peripherally
      acting mu opioid receptor antagonists), have become available and have proven
      beneficial for use with postoperative ileus.

PMID- 22385599
TI  - Pearls and pitfalls of single-bundle transtibial posterior cruciate ligament
      reconstruction.
AB  - Posterior cruciate ligament (PCL) injuries are rare, but they often require
      reconstruction, especially in the setting of combined ligamentous knee injury.
      Single-bundle transtibial PCL reconstruction is 1 technique for restoring this
      important ligament. However, this procedure is technically demanding, and
      complications can occur if poor techniques are used. This article analyzes the
      potential pitfalls of this procedure and presents the pearls that may ease the
      technical demands and reduce the risk of avoidable complications.

PMID- 22385600
TI  - Vacuum-assisted minimally invasive biopsy of soft-tissue tumors.

PMID- 22385601
TI  - Relationship between deep vein thrombosis and pulmonary embolism following THA
      and TKA.
AB  - Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty
      (TKA) are at risk for venous thromboembolisms, including deep vein thrombosis and
      pulmonary embolism. Most deep vein thromboses are asymptomatic, but they can lead
      to long-term morbidity to the same extent as symptomatic events. The risk of
      complications of venous thromboembolisms depends on the location of thrombi;
      potential long-term complications include recurrent venous thromboembolism,
      postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Risk
      of recurrence persists for several years after the initial event. Approximately
      20% of recurrent events are pulmonary embolisms, and approximately half of those
      are fatal. The causal relationship between deep vein thrombosis and pulmonary
      embolism remains controversial. Some consider them distinct clinical entities,
      while others have found asymptomatic distal deep vein thrombosis to be associated
      with elevated risk of developing pulmonary embolism. Unique coagulation factors
      may be associated with orthopedic surgery patients that differentiate them from
      patients undergoing other types of surgery. Symptomatic and asymptomatic deep
      vein thrombosis can lead to the development of recurrent venous thromboembolism,
      pulmonary embolism, postthrombotic syndrome, and chronic thromboembolic pulmonary
      hypertension, all of which are associated with reduced quality of life and
      increased health care expenditures. Thromboprophylaxis is therefore important in
      patients undergoing THA or TKA. However, traditional anticoagulants are not
      ideal, particularly for long-term use. Orthopedic surgeons should be aware of the
      causes and potential sequelae of venous thromboembolism and of the new
      thromboprophylactic agents that can help prevent it.

PMID- 22385603
TI  - Lipid-anchored drugs for delivery into subcellular compartments.
AB  - Bioavailability is a quantitative measure of the capacity of a drug to reach
      systemic circulation. However, if a drug target is localized in a subcellular
      organelle, then the drug may not be able to reach it and the effect of the drug
      will not be attained. Although most drug targets are localized within
      intracellular compartments, specific targeting of drugs at the subcellular level
      is not well established. Membrane proteins, lipids, nutrients and some pathogens
      are internalized into the cell to be targeted to distinct subcellular
      compartments via membrane trafficking. Recent advances have identified novel
      methods of subcellular drug targeting, involving the use of conjugation to
      ligands of cell surface receptors or to lipid anchors. In this review, we focus
      on the importance of subcellular targeting of drugs, in particular, the mechanism
      of lipid-anchoring as a novel strategy and its potential application for the
      treatment of several diseases.

PMID- 22385604
TI  - Evaluation of the biocompatibility of a coating material for an implantable
      bladder volume sensor.
AB  - As the applications for implantable medical devices have increased, the need for
      biocompatible packaging materials has become important. Recently, we reported an
      implantable sensor for real-time monitoring of the changes in bladder volume,
      which necessitated finding a safe coating material for use in bladder tissue. At
      present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS)
      and parylene-C are used in biomedical devices or as coating materials, owing to
      their excellent safety in various medical fields. However, few studies have
      assessed their safety in bladder tissue, therefore, we evaluated the
      biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials
      turned out to be safe in in vitro tests of live/dead staining and cell viability.
      In vivo tests with hematoxylin and eosin and immunofluorescence staining with
      MAC387 showed no persistent inflammation. Therefore, we consider that the three
      materials are biocompatible in bladder tissue. Despite this safety, however, PEG
      has biodegradable characteristics and thus is not suitable for use as packaging.
      We suggest that PDMS and parylene-C can be used as safe coating materials for the
      implantable bladder volume sensor reported previously.

PMID- 22385605
TI  - Comparison of Gd-Bz-TTDA, Gd-EOB-DTPA, and Gd-BOPTA for dynamic MR imaging of the
      liver in rat models.
AB  - To evaluate the competitive potential of a new lipophilic paramagnetic complex,
      Gd-Bz-TTDA [4-benzyl-3,6,10-tri (carboxymethyl)-3,6,10-triazado-decanedioic acid]
      compared with two other commercially available MR hepatobiliary contrast agents,
      gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB-DTPA), dynamic MR
      imaging studies were performed on normal and hepatocellular carcinoma (HCC) rat
      models using a 1.5-Tesla MR scanner. The results indicate that normal rats that
      were injected with 0.1 mmol/kg Gd-Bz-TTDA showed significantly more intense and
      persistent liver enhancement than those that were injected with the same dose of
      Gd-EOB-DTPA or Gd-BOPTA. All of these agents showed similar enhancement patterns
      in the implanted HCC. The liver-lesion contrast-to-noise ratios were higher and
      more persistent in rats that were injected with Gd-Bz-TTDA. These results
      indicate that Gd-Bz-TTDA is comparable with the commercially available
      hepatobiliary agents, Gd-EOB-DTPA and Gd-BOPTA, and can result in more intense
      and prolonged liver enhancement while still providing better liver-lesion
      discrimination. These results warrant further large-scale studies.

PMID- 22385606
TI  - Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and
      oral cancer.
AB  - Isocitrate dehydrogenase (IDH) encodes a nicotinamide adenine dinucleotide
      phosphate+-dependent enzyme for oxidative decarboxylation of isocitrate and has
      an essential role in the tricarboxylic acid cycle. Mutations of IDH1 and IDH2
      have been identified in patients with glioma, leukemia, and other cancers.
      However, the incidence of IDH mutations in acute myeloid leukemia in Taiwan is
      much lower than that reported in Western countries. The reason for the difference
      is unknown and its clinical implications remain unclear. Acute lymphoblastic
      leukemia (ALL) is a heterogenous hematopoietic malignancy. Oral squamous cell
      carcinoma (OSCC) results from chronic carcinogen exposures and is highly
      prevalent in trucking workers, especially in southern Taiwan. Subtypes of both
      diseases require specific treatments, and molecular markers for developing
      tailored treatments are limited. High-resolution melting (HRM) analysis is now a
      widely used methodology for rapid, accurate, and low-cost mutation scanning. In
      this study, 90 adults with OSC and 31 children with ALL were scanned by HRM
      analysis for IDH1 and IDH2 mutation hot spots. In ALL, the allele frequency was
      3.23% in both IDH1 and IDH2. In OSCC, the allele frequency was 2.22% in IDH2. A
      synonymous mutation over pG313 (c.939A > G) of IDH2 was found in both pediatric
      ALL and adult OSCC. Therefore, we concluded that mutations of IDH are uncommon in
      ALL and OSCC and are apparently not a major consideration when selecting
      treatment modalities.

PMID- 22385607
TI  - Overexpression of annexin 1 in the development and differentiation of urothelial
      carcinoma.
AB  - This study investigates the expression of annexin 1 in urothelial carcinoma (UC)
      and its relation with clinicopathologic factors, and evaluates its potential
      clinical significance. Annexin 1 expression was analyzed by immunohistochemical
      staining with manual tissue microarrays and Western blot in UC.
      Immunohistochemical analysis of UC in tissue microarrays showed that annexin 1
      protein was 76.5% (150/196) positive, which was markedly increased compared with
      that in the normal urothelium 20.8% (5/24) (p < 0.01). In addition, the positive
      expression rate of annexin 1 was higher in the high-grade UC (81.7%; 143/175)
      than in the low-grade UC (33.3%; 7/21). Western blot revealed that the expression
      of annexin 1 was low in low-grade UC, and markedly increased in high-grade UC. In
      conclusion, annexin 1 overexpression is observed in UC, which suggests it may be
      associated with tumorigenesis and its expression correlates with the
      differentiation of UC.

PMID- 22385608
TI  - Severity of fatty liver on ultrasound correlates with metabolic and
      cardiovascular risk.
AB  - Non-alcoholic fatty liver disease is associated with an increased risk of
      metabolic and cardiovascular diseases. Whether the severity of fatty liver on
      ultrasound correlates with metabolic or cardiovascular risk remains unclear. A
      total of 1000 people receiving health examinations were enrolled, and 126 were
      excluded due to the presence of HBsAg, anti-HCV, known hepatic disorders or
      alcohol use (>140 g/wk). Significant fatty liver consisted of moderate and severe
      fatty liver on ultrasound. The definition of central obesity was modified to a
      waist circumference of >90 cm in men and >80 cm in women. Framingham risk score
      was used to estimate the risk of cardiovascular disease. A total of 874 subjects
      (485 women and 388 men with a mean age of 52.07 +/- 11.68 years) were included in
      the final analysis. By using logistic regression analyses stratified by gender,
      the odds ratio for the prevalence of diabetes mellitus, metabolic syndrome and
      risk of cardiovascular disease increased with increasing fatty liver status in
      both genders (p <= 0.001). The difference was not only present between
      individuals with fatty liver vs. non-fatty liver but also between the mild fatty
      liver and significant fatty liver groups (p < 0.05). In conclusion, the severity
      of fatty liver on ultrasound could be useful for the risk stratification of
      metabolic syndrome, diabetes mellitus and cardiovascular disease in clinical
      practice.

PMID- 22385609
TI  - Adenoma malignum of the uterine cervix: Clinicopathologic analysis of 18 cases.
AB  - The aim of this study was to evaluate the clinical and pathologic features of a
      rare tumor (adenoma malignum, AM). We retrospectively analyzed the medical
      records of 18 patients diagnosed with AM at a single institute between March 1992
      and November 2009. The median age of the patients was 45.8 years (range 29-76
      years) and the mean follow-up period was 49.2 months (range 4-168 months). A
      preoperative cytologic diagnosis (Papanicolaou smear) of AM was made in 22.2%
      (4/18) of the cases. Ten (55.6%) of the 18 patients were misdiagnosed with other
      benign diseases and underwent hysterectomies, which confirmed AM. Sixteen
      patients with AM were in the early stage (IB1, 11/18; IB2, 5/18) and the other
      two patients were in the advanced stage. Fourteen of 18 patients (77.8%) had pure
      AM alone. Adjuvant therapy was administered to eight of the patients (44.4%) with
      AM. The recurrence rate was zero, but the disease progressed in two of the
      patients (11.1%), who died of the disease. The 5-year survival rate was 88.8%. A
      cytological diagnosis of AM based on a Papanicolaou smear is rarely made; a deep
      biopsy (cone biopsy or endocervical curettage) is necessary to diagnose this rare
      tumor preoperatively when there is any clinical suspicion of AM.

PMID- 22385610
TI  - Relationship between red cell distribution width and echocardiographic parameters
      in patients with diastolic heart failure.
AB  - Red cell distribution width (RDW) was found to be a prognostic marker in heart
      failure patients. The aim of the study was to investigate the relationship
      between RDW and echocardiographic parameters in diastolic heart failure (DHF).
      Seventy-one consecutive DHF patients (26 men) and 50 controls (21 men) were
      included in the study. All of the study population underwent echocardiographic
      evaluation, and blood samples were obtained. RDW and N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) values were significantly higher, whereas there
      was an increasing trend for high-sensitivity C-reactive protein levels in DHF
      patients than those in controls (p<0.001, p<0.001, and p=0.064, respectively).
      All of the echocardiographic parameters evaluating diastolic function were more
      deteriorated in the DHF group. Patients who had an RDW value greater than the
      cutoff point also had higher NT-proBNP levels, an elevated ratio of mitral peak
      velocity of early diastolic filling to early diastolic mitral annular velocity,
      and increased estimated pulmonary capillary wedge pressures by tissue Doppler
      parameters, but lower creatinine clearance (p<0.05 for all). According to the
      cutoff values calculated using receiver operating characteristic analysis,
      RDW>13.6% and NT-proBNP>125pg/mL have high diagnostic accuracy for predicting
      DHF. RDW values were increased in the DHF population. Our results suggest that
      the high RDW levels in patients with DHF may be related to increased
      neurohormonal activity, impaired renal functions, and elevated filling pressure,
      but not to increased inflammation.

PMID- 22385611
TI  - Therapy-related acute lymphoblastic leukemia with t(4;11)(q21;q23) masqueraded as
      marrow lymphocytosis in a patient with breast cancer.
AB  - Therapy-related acute leukemia develops in patients after chemotherapy and/or
      radiotherapy for a prior cancer, and most cases are acute myeloid leukemia with a
      much lower frequency of acute lymphoblastic leukemia (ALL). One unique feature of
      these therapy-related ALL (t-ALL) is an increased incidence of chromosome band
      11q23 aberrations as compared with de novo ALL. In adult female patients, breast
      cancer is the most common primary cancer. Herein, we report the case of a 49-year
      old Taiwanese lady who developed t-ALL with t(4;11)(q21;q23) 16 months after
      cyclophosphamide, epirubicin, and 5-fluorouracil chemotherapy for her breast
      cancer. The unusual feature is that the t-ALL was heralded 4 months ago by marrow
      lymphocytosis comprising atypical small lymphocytes with condensed chromatin
      mimicking a B-cell chronic lymphoproliferative disorder. Retrospective studies
      using additional antibodies for immunophenotyping and PCR-based clonality study
      for immunoglobulin gene rearrangement showed that these atypical small
      lymphocytes shared similar features with the leukemic blasts at the frank
      leukemic stage. Our results suggest that these atypical small lymphocytes are
      lymphoblasts in disguise and that the clinicopathological correlations with
      ancillary pathological studies are important to reach a definitive diagnosis of
      such an unusual case.

PMID- 22385612
TI  - Antibiotic-treated Streptococcus sanguinis intracranial mycotic aneurysm.
AB  - We report the case of a woman 33 years of age with infective endocarditis-related
      intracranial mycotic aneurysm (IMA) caused by a Streptococcus sanguinis
      infection. The clinical diagnosis was confirmed by the findings of magnetic
      resonance imaging, magnetic resonance angiographic (MRA) studies,
      echocardiographic studies, and a positive blood culture result. She underwent
      antimicrobial treatment only (ceftriaxone intravenously for 8 weeks and
      penicillin V orally for 6 weeks). The regression and disappearance of IMA were
      demonstrated by a series of MRA follow-up studies.

PMID- 22385613
TI  - An unusual slow-growing malignant orbital solitary fibrous tumor.

PMID- 22385614
TI  - Free energy calculations on snake venom metalloproteinase BaP1.
AB  - BaP1 is a snake venom metalloproteinase from the venom of Bothrops asper, showing
      high structural homology with the catalytic domain of human adamalysins and
      matrix metalloproteinases. It induces the release of cytokines, like interleukin
      1 and tumor necrosis factor alpha. Recently, the high-resolution crystal
      structure of BaP1 with a bound inhibitor became available, representing an
      interesting model concerning inhibitor design for medicinally important
      metalloproteinases such as tumor necrosis factor alpha-converting enzyme and
      MMP13. We here use computational modeling to gain a better understanding about
      the binding properties of various ligands to BaP1, with a focus on computing
      ligand binding free energies. The obtained results should be of general
      significance for future research on medicinally important metalloproteinases. We
      have investigated the binding of the original inhibitor in detail and calculated
      its binding strength using MMP/GBSA free energy calculations. Additionally, the
      binding strengths of alternative ligands have been computed, and two of them are
      predicted and experimentally verified to strongly inhibit the enzyme. A
      suggestion for chemical modifications of BaP1 inhibitors could be made to guide
      future synthesis efforts. Furthermore, a contribution to the proteolytic reaction
      mechanism of metzincins is given. The pK value of the catalytically active
      glutamic acid residue 143 has been found to be significantly raised when compared
      with a free glutamate side chain. Calculations on other matrix metalloproteinases
      confirmed that this is not confined to BaP1, but seems to be a common feature of
      metzincins.

PMID- 22385615
TI  - Actin-dependent activation of serum response factor in T cells by the viral
      oncoprotein tip.
AB  - Serum response factor (SRF) acts as a multifunctional transcription factor
      regulated by mutually exclusive interactions with ternary complex factors (TCFs)
      or myocardin-related transcription factors (MRTFs). Binding of Rho- and actin
      regulated MRTF:SRF complexes to target gene promoters requires an SRF-binding
      site only, whereas MAPK-regulated TCF:SRF complexes in addition rely on flanking
      sequences present in the serum response element (SRE). Here, we report on the
      activation of an SRE luciferase reporter by Tip, the viral oncoprotein
      essentially contributing to human T-cell transformation by Herpesvirus saimiri.
      SRE activation in Tip-expressing Jurkat T cells could not be attributed to
      triggering of the MAPK pathway. Therefore, we further analyzed the contribution
      of MRTF complexes. Indeed, Tip also activated a reporter construct responsive to
      MRTF:SRF. Activation of this reporter was abrogated by overexpression of a
      dominant negative mutant of the MRTF-family member MAL. Moreover, enrichment of
      monomeric actin suppressed the Tip-induced reporter activity. Further upstream,
      the Rho-family GTPase Rac, was found to be required for MRTF:SRF reporter
      activation by Tip. Initiation of this pathway was strictly dependent on Tip's
      ability to interact with Lck and on the activity of this Src-family kinase.
      Independent of Tip, T-cell stimulation orchestrates Src-family kinase, MAPK and
      actin pathways to induce SRF. These findings establish actin-regulated
      transcription in human T cells and suggest its role in viral oncogenesis.

PMID- 22385616
TI  - Adrenal insufficiency following bariatric surgery.
AB  - A 35-year-old woman with morbid obesity and amenorrhoea underwent a bilo
      pancreatic diversion (BPD). Surgery was successful with good weight loss,
      restoration of menstruation and almost immediately she conceived for the first
      time. She was commenced on routine vitamin supplements after surgery but failed
      to attend follow-up clinic. Five years later, she presented with limb girdle
      pains, lethargy, night blindness, skin pigmentation, amenorrhoea and dizziness.
      She had stopped taking supplements prescribed after the surgery. Investigations
      showed severe vitamin A and D deficiency along with iron and calcium deficiency.
      Her cholesterol was low at 3.5 mmol L-1. Despite aggressive vitamin replacement,
      she continued to complain of lethargy and dizziness. Subsequently, three short
      adrenocorticotropic hormone-stimulation tests were suboptimal (basal cortisol:
      196, 185 and 223 nmol L-1; 30 min cortisol: 421, 453 and 435 nmol L-1). She was
      subsequently commenced on adrenal replacement and her symptoms resolved and she
      conceived. We describe for the first time in the literature the unexpected
      finding of adrenal insufficiency following a BPD.

PMID- 22385617
TI  - High gene flow and outcrossing within populations of two cryptic fungal pathogens
      on a native and non-native host in Cameroon.
AB  - In this study, we determined the genetic diversity of 126 isolates representing
      both Lasiodiplodia theobromae and Lasiodiplodia pseudotheobromae, collected from
      Theobroma cacao and Terminalia spp. in Cameroon, using simple sequence repeat
      (SSR) markers. SSR alleles showed clear genetic distinction between L. theobromae
      and L. pseudotheobromae, supporting their earlier separation as sister species.
      Both L. theobromae and L. pseudotheobromae populations from Cameroon had high
      levels of gene diversity, moderate degrees of genotypic diversity, and high
      levels of gene flow between isolates from T. cacao and Terminalia spp. There was
      no evidence for geographic substructure in these populations across the region
      studied, and the SSR alleles were randomly associated in both species, suggesting
      outcrossing. The significant levels of aggressiveness, evolutionary potential
      represented by high levels of diversity, outcrossing and gene flow between
      geographically and host defined populations, identify these fungi as high-risk
      pathogens for their native and non-native hosts in Cameroon.

PMID- 22385618
TI  - A molecular approach to explore the extent of the threatened fungus Hypocreopsis
      rhododendri within wood.
AB  - Hypocreopsis rhododendri is a rare fungus that grows on woody stems in
      hyperoceanic climax scrub on the west coasts of Britain, Ireland, and France.
      Knowledge of the distribution and abundance of the fungus is based entirely on
      sporocarp records; it does not account for any occurrence as vegetative mycelia.
      To address this issue, a H. rhododendri-specific polymerase chain reaction (PCR)
      was developed and used to assay Corylus avellana (hazel) stems for the presence
      of H. rhododendri mycelia. The primers ITSHrF and ITSHrR were designed within the
      internal transcribed spacer 2 region, and their specificity to H. rhododendri was
      established by their failure to amplify DNA extracted from 14 other Hypocreaceae
      species. The sensitivity of the assay was demonstrated by amplifying DNA
      extracted from 4 mg C. avellana wood spiked with 0.0013 % H. rhododendri
      mycelium. Samples of wood and bark were then taken from around and directly
      underneath 11 H. rhododendri sporocarps and assayed for the presence of H.
      rhododendri. PCR products were obtained from a third of the surface bark samples,
      but only one faint product was obtained from 70 samples taken from beneath the
      outer bark. The results support the view that H. rhododendri does not form
      mycelia within stems. We suggest that H. rhododendri is not a saprotrophic
      fungus, but instead appears to be a parasitic on the wood decay fungus
      Hymenochaete corrugata, with which it always occurs. Evidence that tissue of H.
      corrugata is present within the sporocarps of H. rhododendri is discussed.

PMID- 22385619
TI  - Differential expression of the putative Kex2 processed and secreted aspartic
      proteinase gene family of Cryphonectria parasitica.
AB  - Kex2-silenced strains of Cryphonectria parasitica, the ascomycete causal agent of
      chestnut blight, show a significant reduction in virulence, reduced sexual and
      asexual sporulation and reductions in mating and fertility. Due to this and the
      known involvement of Kex2 in the processing of important proproteins in other
      systems, we searched the whole C. parasitica genome for putative Kex2 substrates.
      Out of 1299 open reading frames (ORFs) predicted to be secreted, 222 ORFs were
      identified as potential Kex2 substrates by this screen. Within the putative
      substrates we identified cell wall modifying proteins, putative proteinases,
      lipases, esterases, and oxidoreductases. This in silico screen also uncovered a
      family of nine secreted aspartic proteinases (SAPs) of C. parasitica. Northern
      blot analyses of this gene family showed differential expression when exposed to
      chestnut wood and Cryphonectria hypovirus 1 (CHV1). Due to the reduction in
      fungal virulence known to be caused upon hypoviral infection of C. parasitica,
      the differential gene expression observed, and the known involvement of SAPs in
      virulence in other systems, we conducted deletion analyses of four of these
      proteinases, representing different expression patterns. Deletion of each of the
      four SAPs did not affect growth rates, sporulation or virulence, suggesting that
      none of the considered SAPs is essential for the full development or virulence of
      C. parasitica under the conditions tested.

PMID- 22385620
TI  - Germling fusion via conidial anastomosis tubes in the grey mould Botrytis cinerea
      requires NADPH oxidase activity.
AB  - In many filamentous ascomycete species, the early steps of colony development
      include fusion between germinating vegetative spores (conidial germlings). Often
      these fusion events are mediated by specialized hyphal structures, so-called
      conidial anastomosis tubes (CATs). Here, we show that germling fusion in the grey
      mould Botrytis cinerea is mediated by hyphal structures possessing the typical
      features of CATs. Formation of these structures is delayed when spores are
      germinating on complex media compared to growth on poor substrates. Fusion
      frequency is also influenced by the growth conditions of the precultures from
      which spores were obtained. During germination on hydrophobic plant surfaces,
      which induce pathogenic development, CAT formation is significantly suppressed.
      Screening of existing B. cinerea gene knockout mutants identified strains lacking
      the NADPH oxidase BcNoxA or the potential Nox regulator BcNoxR as fusion
      deficient, suggesting a potential role of reactive oxygen species (ROS)
      signalling in CAT formation and fusion.

PMID- 22385621
TI  - Frequent circumarctic and rare transequatorial dispersals in the lichenised
      agaric genus Lichenomphalia (Hygrophoraceae, Basidiomycota).
AB  - Species of the genus Lichenomphalia are mostly restricted to arctic-alpine
      environments with the exception of Lichenomphalia umbellifera which is also
      common in northern forests. Although Lichenomphalia species inhabit vast regions
      in several continents, no information is available on their genetic variation
      across geographic regions and the underlying population-phylogenetic patterns. We
      collected samples from arctic and subarctic regions, as well as from newly
      discovered subantarctic localities for the genus. Phylogenetic, nonparametric
      permutation methods, and coalescent analyses were used to assess phylogeny and
      population divergence and to estimate the extent and direction of gene flow among
      distinct geographic populations. All known species formed monophyletic groups,
      supporting their morphology-based delimitation. In addition, we found two
      subantarctic phylogenetic species (Lichenomphalia sp. and Lichenomphalia aff.
      umbellifera), of which the latter formed a well-supported sister group to L.
      umbellifera. We found no significant genetic differentiation among conspecific
      North American and Eurasian populations in Lichenomphalia. We detected high
      intercontinental gene flow within the northern polar region, suggesting rapid
      (re)colonisation of suitable habitats in response to climatic fluctuations and
      preventing pronounced genetic differentiation. On the other hand, our
      phylogenetic analyses suggest that dispersal between northern circumpolar and
      subantarctic areas likely happened very rarely and led to the establishment and
      subsequent divergence of lineages. Due to limited sampling in the Southern
      Hemisphere, it is currently uncertain whether the northern lineages occur in
      Gondwanan regions. On the other hand, our results strongly suggest that the
      southern lineages do not occur in the circumpolar north. Although rare
      transequatorial dispersal and subsequent isolation may explain the emergence of
      at least two subantarctic phylogenetic species lineages in Lichenomphalia, more
      samples from the Southern Hemisphere are needed to better understand the
      phylogeographic history of the genus.

PMID- 22385622
TI  - Patterns of fungal diversity in New Zealand Nothofagus forests.
AB  - The development of protocols for the conservation of fungi requires knowledge of
      the factors controlling their distribution, diversity, and community composition.
      Here we compare patterns of variation in fungal communities across New Zealand's
      Nothofagus forests, reportedly the most myco-diverse in New Zealand and hence
      potentially key to effective conservation of fungi in New Zealand. Diversity of
      leaf endophytic fungi, as assessed by culturing on agar plates, is assessed for
      three Nothofagus sp. growing in mixed stands from four sites. Host species was
      found to have a greater influence on fungal community assemblage than site. The
      leaf endophyte communities associated with Nothofagus solandri and Nothofagus
      fusca (both Nothofagus subgenus Fuscopora), were more similar to each other than
      either were to the community associated with Nothofagus menziesii (Nothofagus
      subgenus Lophozonia). The broad taxonomic groups isolated, identified on the
      basis of internal transcribed spacer (ITS) sequences, were similar to those found
      in similar studies from other parts of the world, and from an earlier study on
      the endophyte diversity in four podocarp species from New Zealand, but there were
      few matches at species level. Average levels of endophyte species diversity
      associated with single Nothofagus species and single podocarp species were
      similar, despite historical literature and collection data recording more than
      twice as many fungal species on average from the Nothofagus species. The
      significance of these findings to fungal conservation is discussed.

PMID- 22385623
TI  - Effect of salicylic acid on Fusarium graminearum, the major causal agent of
      fusarium head blight in wheat.
AB  - Salicylic acid (SA) is one of the key signal molecules in regulating plant
      resistance to diverse pathogens. In Arabidopsis thaliana, it is predominantly
      associated with resistance against biotrophic and hemibiotrophic pathogens, and
      triggering systemic acquired resistance. In contrast, the effect of SA on the
      defence efficiency of wheat against fusarium head blight (FHB) and its causal
      agent, Fusarium graminearum, is still poorly understood. Here we show that the F.
      graminearum mycelial growth and conidia germination were significantly inhibited,
      and eventually halted in the presence of increasing concentration of SA in both
      liquid and solid media. Addition of SA also significantly reduced the production
      of the mycotoxin deoxynivalenol (DON). However the inhibitory effect of SA
      required acidic growth conditions to be observed while basic conditions allowed
      F. graminearum to use SA as a carbon source. High performance liquid
      chromatography (HPLC) analysis confirmed the capacity of F. graminearum to
      metabolize SA. To better understand the effect of SA on F. graminearum mycelial
      growth, we have compared the expression profiles of SA-treated and untreated F.
      graminearum liquid cultures after 8 and 24 h of treatment, using an F.
      graminearum custom-commercial microarray. The microarray analysis suggested that
      F. graminearum can metabolize SA through either the catechol or gentisate
      pathways that are present in some fungal species. Inoculation of F. graminearum
      conidia in a SA-containing solution has led to reduced FHB symptoms in the very
      susceptible Triticum aestivum cv. Roblin. In contrast, no inhibition was observed
      when SA and conidia were inoculated sequentially. The expression patterns for the
      wheat PR1, NPR1, Pdf1.2, and PR4 genes, a group of indicator genes for the
      defence response, suggested that SA-induced resistance contributed little to the
      reduction of symptoms in our assay conditions. Our results demonstrate that,
      although F. graminearum has the capacity to metabolize SA, SA has a significant
      and direct impact on F. graminearum through a reduction in efficiency of
      germination and growth at higher concentrations.

PMID- 22385624
TI  - Both mating types in the heterothallic fungus Ophiostoma quercus contain MAT1-1
      and MAT1-2 genes.
AB  - In heterothallic Ascomycota, two opposite but distinct mating types control all
      sexual processes. Using mating crosses, mating types were assigned to ten
      isolates of the heterothallic fungal species Ophiostoma quercus. Primers were
      subsequently designed to target the MAT1-1-1, MAT1-1-3 (of the mating type 1
      idiomorph), and MAT1-2-1 (of the mating type 2 idiomorph) genes in these
      isolates. Results showed that all isolates contained the full gene sequence for
      the MAT1-2-1 gene. In addition, fragments of the MAT1-1-1 and MAT1-1-3 genes were
      sequenced from all isolates. These results were unexpected, as each isolate from
      a heterothallic species would typically contain only one of the two possible MAT
      idiomorphs.

PMID- 22385625
TI  - Culture of Metarhizium robertsii on salicylic-acid supplemented medium induces
      increased conidial thermotolerance.
AB  - Salicylic acid (SA), a cell-signaling metabolite in plants, is involved in
      resistance of plants to pathogens and environmental stresses; however, there is
      little information available on the responses of fungi to SA. Conidia of
      Metarhizium robertsii (ARSEF 2575) (Hypocreales: Clavicipitaceae) were produced
      on potato dextrose agar medium plus yeast extract (PDAY) supplemented with 1, 2,
      4, or 8 mM SA (pH adjusted to 6.9) and incubated under constant-dark conditions.
      Then the tolerance of conidia against wet heat (45  degrees C, 3 h) and UV-B
      radiation (7.0 kJ m(-2)) was tested. For comparison, conidia were also produced
      on minimal medium (MM) that contained no carbon source (carbon starvation), a
      condition known to induce elevated conidial tolerance to heat and UV-B radiation
      in M. robertsii. The heat tolerance of conidia produced on PDAY containing 1, 2,
      or 4 mM SA were two-fold higher than that of conidia produced on PDAY alone;
      which is the same level of thermotolerance induced by growth on MM. Conidia
      produced on PDAY with 8 mM SA, however, did not exhibit increased heat tolerance.
      Growth on PDAY + SA did not increase conidial UV-B tolerance at any of the SA
      concentrations tested. The conidial yields of M. robertsii produced on PDAY with
      all levels of SA were somewhat reduced in comparison to the yield on PDAY alone.
      Nevertheless, conidial yields on PDAY + SA were 20-40 times greater than that
      obtained on MM alone. In conclusion, M. robertsii conidia produced on PDAY medium
      containing low concentrations of SA demonstrated increased tolerance to heat, but
      not to UV-B radiation. In comparison to PDAY alone, SA-amended PDAY afforded
      somewhat reduced conidial yields; however, in a mass-production situation, yield
      reductions would be offset by the fact that the conidia obtained would have
      relatively high heat tolerance.

PMID- 22385626
TI  - Expression of novel beta-glucanase Cel12A from Stachybotrys atra in bacterial and
      fungal hosts.
AB  - beta-glucanase Cel12A from Stachybotrys atra has been cloned and expressed in
      Aspergillus niger. The purified enzyme showed high activity of beta-1,3-1,4-mixed
      glucans, was also active on carboxymethylcellulose (CMC), while it did not
      hydrolyze crystalline cellulose or beta-1,3 glucans as laminarin. Cel12A showed a
      marked substrate preference for beta-1,3-1,4 glucans, showing maximum activity on
      barley beta-glucans (27.69 U mg(-1)) while the activity on CMC was much lower
      (0.51 U mg(-1)). Analysis by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE), isoelectric focussing (IEF), and zymography showed
      the recombinant enzyme has apparent molecular weight of 24 kDa and a pI of 8.2.
      Optimal temperature and pH for enzyme activity were 50 degrees C and pH 6.5. Thin
      layer chromatography analysis showed that major hydrolysis products from barley
      beta-glucan and lichean were 3-O-beta-cellotriosyl-D-glucose and 3-O-beta
      cellobiosyl-D-glucose, while glucose and cellobiose were released in smaller
      amounts. The amino acid sequence deduced from cel12A revealed that it is a single
      domain enzyme belonging to the GH12 family, a family that contains several
      endoglucanases with substrate preference for beta-1,3-1,4 glucans. We believe
      that S. atra Cel12A should be considered as a lichenase-like or nontypical
      endoglucanase.

PMID- 22385627
TI  - Phylogeography of the cosmopolitan fungus Aspergillus flavus: is everything
      everywhere?
AB  - Aspergillus flavus is one of the most common fungal eukaryotes on the planet. It
      is notorious for production of aflatoxins, for causing aspergillosis in humans
      and animals, and as an opportunistic pathogen of animals and plants. Its role in
      marine habitats is unclear. Until now, little phylogeographic structure has been
      detected for the species, except at very local scales, and it appears to fit the
      classic dictum of microbial biogeography: Everything is everywhere. Here we use
      genetic relationships among isolates to determine phylogeographic structure,
      mating types, and differences in preferences for: marine vs. terrestrial
      habitats, various substrates, and clinical vs. nonclinical environments.
      Phylogenetic relationships among isolates were estimated using amplified fragment
      length polymorphisms (AFLPs) and mating types were determined for a worldwide
      sample of A. flavus isolates from diverse substrates and geographic locations.
      All isolates composed a single population, with no significant differentiation of
      marine vs. terrestrial isolates, clinical vs. environmental isolates, or
      association with substrate or geographic origin. There was evidence for local
      dominance of a single clade, probably clonal in origin and short-lived. The
      proportion of mating types was 1:1, supporting the hypothesis of recombination in
      natural populations. However, a high proportion of clinical isolates were MAT1-1
      (85%), suggesting that a gene linked to the MAT1-1 idiomorph could play a role in
      pathogenicity. This study suggests that a more appropriate description of the
      phylogeography of A. flavus is 'everything is everywhere, but not all the time.'

PMID- 22385628
TI  - Successful treatment of systemic capillary leak syndrome with intravenous
      immunoglobulins.

PMID- 22385629
TI  - Antigen-specific effector CD8 T cells regulate allergic responses via IFN-gamma
      and dendritic cell function.
AB  - BACKGROUND: Previous studies have shown that CD8 T cells can both prevent and
      cause allergic responses. However, the underlying mechanisms remain to be
      elucidated. OBJECTIVE: We aim to investigate the potential of CD8 T cells with
      different IFN-gamma expressions to modulate the elicitation of allergic
      inflammation following ovalbumin (OVA) challenge and investigate the underlying
      mechanisms. METHODS: To study the role of IFN-gamma in the effect of CD8 T cells,
      effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-gamma(-/-)OT-I
      mice were transferred to OVA-sensitized mice the day before 3 challenges with
      OVA. The effect on lung dendritic cells (DCs) exerted by CD8 T cells was studied
      with ex vivo culture of sorted DCs from treatment mice with CD4 T cells. RESULTS:
      Effector OT-I, but not IFN-gamma(-/-)OT-I CD8 T cells, attenuated eosinophilia
      and mucus secretion in the lungs of sensitized mice in an antigen-specific
      manner. Effector IFN-gamma(-/-)OT-I CD8 T cells displayed a Tc2-/Tc17-biased
      phenotype with weaker cytotoxicity and were able to both induce and exacerbate
      eosinophilia as well as neutrophilia. OT-I CD8 T cells increased the ability of
      lung CD11b(+)CD103(-) DCs to both prime the differentiation of naive OVA-specific
      CD4 T cells toward a T(H)1 phenotype and enhance IFN-gamma production by antigen
      experienced lung CD4 T cells. CONCLUSION: Effector CD8 T cells attenuate
      pulmonary inflammation and alter the ability of DCs within the allergic lung to
      polarize T cells to a T(H)1 phenotype during a T(H)2 response. In the absence of
      IFN-gamma, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate
      inflammation.

PMID- 22385630
TI  - Age-related differences in clinical outcomes for acute asthma in the United
      States, 2006-2008.
AB  - BACKGROUND: Little is known about the effect of age on acute asthma outcomes.
      OBJECTIVE: We sought to investigate age-related differences in the emergency
      department (ED) presentation and clinical outcomes for patients with acute
      asthma. METHODS: We analyzed the 2006-2008 Nationwide Emergency Department
      Sample, the largest, all-payer, US ED and inpatient database. ED visits for acute
      asthma were identified with a principal diagnosis of International Classification
      of Disease, ninth revision, Clinical Modification code 493.xx. Patients were
      divided into 3 age groups: children (<18 years), younger adults (18-54 years),
      and older adults (>=55 years). The outcome measures were in-hospital all-cause
      mortality, near-fatal asthma-related events (noninvasive or mechanical
      ventilation), hospital charges, admission rates, and hospital length of stay.
      RESULTS: There were an estimated 1,813,000 visits annually for acute asthma from
      approximately 4,700 EDs. The estimated overall annual number of in-hospital
      asthma-related deaths was 1,144 (0.06%); 101 died in the ED, and 1,043 died as
      inpatients. By age group, there were 37 asthma-related deaths per year in
      children, 204 in younger adults, and 903 in older adults. Compared with younger
      adults, older adults had higher mortality, had higher rates of near-fatal asthma
      related events, had higher hospital charges, were more likely to be hospitalized,
      and had a longer hospital length of stay (P < .001 for all). After adjusting for
      comorbidities, older asthmatic patients had a 5-fold increased risk of overall
      mortality (adjusted odds ratio, 5.2; 95% CI, 4.0-6.9), compared with younger
      adults. CONCLUSIONS: Older adults with acute asthma have a substantial burden of
      morbidity and mortality. With the US population aging, there is an urgent need
      for targeted interventions for this high-risk population.

PMID- 22385631
TI  - An update on the role of human dendritic cells in patients with atopic
      dermatitis.
AB  - Dendritic cells (DCs) are without a doubt important key skin cells that connect
      information from the environment with the innate and adaptive immune system.
      Their function is decisive for the initiation and inhibition of immune responses,
      and therefore they play a central role for both the healthy and diseased states
      of the skin. The type, maturation stage, and function of DCs, as well as the
      micromilieu in which they are located and their contact with cellular partners in
      the surrounding area, are important cofactors that direct maintenance of immune
      homeostasis or breakout of inflammatory reactions in patients with chronic
      inflammatory skin diseases, such as atopic dermatitis. Thus better knowledge
      about the exact proinflammatory and anti-inflammatory properties of DCs in
      patients with atopic dermatitis and the disease-specific roles of DC subtypes
      would allow us to target these important immune cells with versatile functions
      for therapeutic purpose.

PMID- 22385632
TI  - Increasing the accuracy of peanut allergy diagnosis by using Ara h 2.
AB  - BACKGROUND: Measurement of whole peanut-specific IgE (sIgE) is often used to
      confirm sensitization but does not reliably predict allergy. Ara h 2 is the
      dominant peanut allergen detected in 90% to 100% of patients with peanut allergy
      and could help improve diagnosis. OBJECTIVES: We sought to determine whether Ara
      h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore
      circumvent the need for an oral food challenge (OFC). METHODS: Infants from the
      population-based HealthNuts study underwent skin prick tests to determine peanut
      sensitization and subsequently underwent a peanut OFC to confirm allergy status.
      In a stratified random sample of 200 infants (100 with peanut allergy and 100
      with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified
      by using fluorescence enzyme immunoassay. RESULTS: By using the previously
      published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a
      corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study
      cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is
      60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut
      allergy compared with only 26% correctly identified by using whole peanut sIgE.
      We report that when using a combined approach of plasma sIgE testing for whole
      peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of
      OFCs required is reduced by almost two thirds. CONCLUSION: Ara h 2 plasma sIgE
      test levels provide higher diagnostic accuracy than whole peanut plasma sIgE
      levels and could be considered a new diagnostic tool to distinguish peanut
      allergy from peanut tolerance, which might reduce the need for an OFC.

PMID- 22385633
TI  - Pediatric severe asthma is characterized by eosinophilia and remodeling without
      T(H)2 cytokines.
AB  - BACKGROUND: The pathology of pediatric severe therapy-resistant asthma (STRA) is
      little understood. OBJECTIVES: We hypothesized that STRA in children is
      characterized by airway eosinophilia and mast cell inflammation and is driven by
      the T(H)2 cytokines IL-4, IL-5, and IL-13. METHODS: Sixty-nine children (mean
      age, 11.8 years; interquartile range, 5.6-17.3 years; patients with STRA, n = 53;
      control subjects, n = 16) underwent fiberoptic bronchoscopy, bronchoalveolar
      lavage (BAL), and endobronchial biopsy. Airway inflammation, remodeling, and BAL
      fluid and biopsy specimen T(H)2 cytokines were quantified. Children with STRA
      also underwent symptom assessment (Asthma Control Test), spirometry, exhaled
      nitric oxide and induced sputum evaluation. RESULTS: Children with STRA had
      significantly increased BAL fluid and biopsy specimen eosinophil counts compared
      with those found in control subjects (BAL fluid, P < .001; biopsy specimen, P <
      .01); within the STRA group, there was marked between-patient variability in
      eosinophilia. Submucosal mast cell, neutrophil, and lymphocyte counts were
      similar in both groups. Reticular basement membrane thickness and airway smooth
      muscle were increased in patients with STRA compared with those found in control
      subjects (P < .0001 and P < .001, respectively). There was no increase in BAL
      fluid IL-4, IL-5, or IL-13 levels in patients with STRA compared with control
      subjects, and these cytokines were rarely detected in induced sputum. Biopsy IL
      5(+) and IL-13(+) cell counts were also not higher in patients with STRA compared
      with those seen in control subjects. The subgroup (n = 15) of children with STRA
      with detectable BAL fluid T(H)2 cytokines had significantly lower lung function
      than those with undetectable BAL fluid T(H)2 cytokines. CONCLUSIONS: STRA in
      children was characterized by remodeling and variable airway eosinophil counts.
      However, unlike in adults, there was no neutrophilia, and despite the wide range
      in eosinophil counts, the T(H)2 mediators that are thought to drive allergic
      asthma were mostly absent.

PMID- 22385634
TI  - House dust bioactivities predict skin prick test reactivity for children with
      high risk of allergy.
AB  - BACKGROUND: Although evidence suggests that ambient exposures to endotoxin and
      other immunostimulants during early life influence allergic risk, efforts to
      understand this host-environment relationship have been hampered by a paucity of
      relevant assays. OBJECTIVES: These investigations determined whether parameters
      of house dust extract (HDE) bioactivity were predictive of allergen skin prick
      test (SPT) reactivity for infants at high risk of allergy participating in the
      Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: We
      conducted a nested case-control study, selecting 99 CCAAPS children who had
      positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects
      with negative SPT results. HDEs were prepared from dust samples collected from
      the subjects' homes at age 1 year. Murine splenocytes and bone marrow-derived
      dendritic cells were incubated with HDEs, and supernatant cytokine concentrations
      were determined by means of ELISA. Alternatively, bone marrow-derived dendritic
      cells were preincubated with HDEs, and then LPS-induced IL-6 responses were
      assessed. HDE endotoxin levels were determined by using the limulus amebocyte
      lysate assay. RESULTS: HDEs derived from the homes of children with positive
      (cases) and negative (control subjects) SPT results had similar bioactivities.
      However, when cases were considered in isolation, HDEs with higher levels of
      bioactivity were significantly associated with children who had lower numbers of
      positive SPT results. Analogous statistical analyses did not identify any
      association between HDE endotoxin levels and the aeroallergen sensitization
      profiles of children included in this study. CONCLUSION: HDE immunostimulatory
      activities predicted the aeroallergen sensitization status of CCAAPS subjects
      better than HDE endotoxin levels. These results provide the first published
      evidence that HDE bioassays have clinical relevance in predicting atopic risk.

PMID- 22385635
TI  - Langerhans cells are critical in epicutaneous sensitization with protein antigen
      via thymic stromal lymphopoietin receptor signaling.
AB  - BACKGROUND: The clarification of cutaneous dendritic cell subset and the role of
      thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with
      protein antigens, as in the development of atopic dermatitis, is a crucial issue.
      OBJECTIVES: Because TSLP is highly expressed in the vicinity of Langerhans cells
      (LCs), we sought to clarify our hypothesis that LCs play an essential role in
      epicutaneous sensitization with protein antigens through TSLP signaling. METHODS:
      By using Langerin-diphtheria toxin receptor knock-in mice and human Langerin
      diphtheria toxin A transgenic mice, we prepared mice deficient in LCs. We also
      prepared mice deficient in TSLP receptors in LCs by using TSLP receptor-deficient
      mice with bone marrow chimeric technique. We applied these mice to an ovalbumin
      (OVA)-induced epicutaneous sensitization model. RESULTS: Upon the epicutaneous
      application of OVA, conditional LC depletion attenuated the development of
      clinical manifestations as well as serum OVA-specific IgE increase, OVA-specific
      T-cell proliferation, and IL-4 mRNA expression in the draining lymph nodes.
      Consistently, even in the steady state, permanent LC depletion resulted in
      decreased serum IgE levels, suggesting that LCs mediate the T(H)2 local
      environment. In addition, mice deficient in TSLP receptors on LCs abrogated the
      induction of OVA-specific IgE levels upon epicutaneous OVA sensitization.
      CONCLUSION: LCs initiate epicutaneous sensitization with protein antigens and
      induce T(H)2-type immune responses via TSLP signaling.

PMID- 22385637
TI  - [Conclusions and recommendations. SESPAS Report 2012].

PMID- 22385636
TI  - [The future of the National Health System and its bedrock, primary care. SESPAS
      Report, 2012].

PMID- 22385638
TI  - [The Catalan Primary Care Forum: a contribution to the health debate].

PMID- 22385639
TI  - [Antimicrobial resistance and virulence: a beneficial relationship for the
      microbial world?].
AB  - While bacterial virulence has experienced a long host/pathogen-dependent
      evolutionary process, antimicrobial resistance has had a very different, shorting
      and changing evolution due to the biological pressure caused by the introduction
      of the antimicrobials in human medicine. This strong pressure has forced the
      microorganisms to adapt to these changing conditions, continuously acquiring or
      developing new resistance mechanisms, causing major changes in cellular functions
      and finally influencing the virulence and bacterial fitness. Multiple factors may
      mediate in the relationship between virulence and resistance. The genes often
      involved in both phenomena have the same transport and dispersion mediums.
      Islands, integrons, transposons and other genetic elements could also facilitate
      the combined selection of virulence and resistance genes. The increase in
      resistance can affect virulence in different ways, mainly depending on the
      bacterial species, the environment, and the mechanism of resistance. This review
      presents the different phenomena in which the genetic mechanism that provides an
      advantage over the antimicrobials directly affects the virulence and fitness,
      such as changes in the structure of the cellular wall, efflux pumps, porins or
      two-component regulatory systems. The co-selection of virulence and antimicrobial
      resistance factors and the relative ease of bacteria to develop compensatory
      mutations can favour, particularly in environments with high antibiotic pressure,
      the emergence of prevalent clones. These can be virulent and with few treatment
      options, and could be a major health problem in the near future.

PMID- 22385640
TI  - The Brugada syndrome mutation A39V does not affect surface expression of neuronal
      rat Cav1.2 channels.
AB  - BACKGROUND: A loss of function of the L-type calcium channel, Cav1.2, results in
      a cardiac specific disease known as Brugada syndrome. Although many Brugada
      syndrome channelopathies reduce channel function, one point mutation in the N
      terminus of Cav1.2 (A39V) has been shown to elicit disease a phenotype because of
      a loss of surface trafficking of the channel. This lack of cell membrane
      expression could not be rescued by the trafficking chaperone Cavbeta. FINDINGS:
      We report that despite the striking loss of trafficking described previously in
      the cardiac Cav1.2 channel, the A39V mutation while in the background of the
      brain isoform traffics and functions normally. We detected no differences in
      biophysical properties between wild type Cav1.2 and A39V-Cav1.2 in the presence
      of either a cardiac (Cavbeta2b), or a neuronal beta subunit (Cavbeta1b). In
      addition, the A39V-Cav1.2 mutant showed a normal Cavbeta2b mediated increase in
      surface expression in tsA-201 cells. CONCLUSIONS: The Brugada syndrome mutation
      A39V when introduced into rat brain Cav1.2 does not trigger the loss-of
      trafficking phenotype seen in a previous study on the human heart isoform of the
      channel.

PMID- 22385641
TI  - Commercially available interactive video games in burn rehabilitation:
      therapeutic potential.
AB  - Commercially available interactive video games (IVG) like the Nintendo WiiTM (NW)
      and PlayStationTMII Eye Toy (PE) are increasingly used in the rehabilitation of
      patients with burn. Such games have gained popularity in burn rehabilitation
      because they encourage range of motion (ROM) while distracting from pain.
      However, IVGs were not originally designed for rehabilitation purposes but rather
      for entertainment and may lack specificity for achieving rehabilitative goals.
      Objectively evaluating the specific demands of IVGs in relation to common burn
      therapy goals will determine their true therapeutic benefit and guide their use
      in burn rehabilitation. Upper extremity (UE) motion of 24 normal children was
      measured using 3D motion analysis during play with the two types of IVGs most
      commonly described for use after burn: NW and PE. Data was analyzed using t-tests
      and One-way Analysis of Variance. Active range of motion for shoulder flexion and
      abduction during play with both PE and NW was within functional range, thus
      supporting the idea that IVGs offer activities with therapeutic potential to
      improve ROM. PE resulted in higher demands and longer duration of UE motion than
      NW, and therefore may be the preferred tool when UE ROM or muscular endurance are
      the goals of rehabilitation. When choosing a suitable IVG for application in
      rehabilitation, the user's impairment together with the therapeutic attributes of
      the IVG should be considered to optimize outcome.

PMID- 22385642
TI  - Quality evaluation of meshed split-thickness skin grafts stored at 4 degrees C in
      isotonic solutions and nutrient media by cell cultures.
AB  - OBJECTIVE: Excess split-skin autografts harvested and meshed during burn surgery
      are often stored at 4 degrees C temporarily for later use. The quality of the
      stored skin is critical to clinical outcome and needs to be assured. METHODS:
      Meshed split-thickness skin graft (mSSG) stored in saline, Hartmann's solution
      and two cell culture media, Dulbecco's Modified Eagle Medium (DMEM) and DMEM/Ham
      F12 (DMEM/F12, 3:1 mixture) were analyzed by trypan blue staining, cell culture
      and microbiological testing through a 28-day time course for cell viability and
      microbial contamination. RESULTS: mSSG samples in all groups showed a progressive
      decrease of cell viability and colony forming efficiency through the time course
      of storage at 4 degrees C. Cell culture media were better than saline and
      Hartmann's solution in maintaining the viability and growth capability of skin
      cells. The viability observed by trypan blue staining did not truly reflect the
      cell growth capacity after storage. mSSG in saline and Hartman's solution
      retained minimal keratinocyte growth potency after 7 days. mSSG in cell culture
      media had significant loss of keratinocyte colony growth potency after 7 days and
      minimal keratinocyte growth after 14 days. Dermal fibroblasts of all groups were
      less tolerant than keratinocytes to the storage. Microbial contaminations were
      common in mSSG harvested from burn surgery. CONCLUSIONS: Culture media instead of
      saline or Hartman's solution should be used for temporary storage of mSSG at 4
      degrees C. The stored mSSS should be used within seven days to have sufficient
      viable number and cell growth efficiency. After then, the efficacy of stored mSSG
      as a source of living cells for wound closure could be full of uncertainty due to
      significant decrease of keratinocyte colony forming efficiency. Precaution should
      be taken during skin harvest and storage to minimize the risk of sample
      contamination. Inclusion of antimicrobial agents in storage solution and
      microbiological testing are advisable to ensure the quality and clinical outcome.

PMID- 22385643
TI  - Selectivity of a bromelain based enzymatic debridement agent: a porcine study.
AB  - BACKGROUND: Debridement of the burn eschar is a cornerstone of burn wound care.
      Rapid enzymatic debridement with a bromelain-based agent (Debriding Gel Dressing
      DGD) has recently been investigated. The current study was designed to further
      investigate the selectivity of DGD to burned eschar in a larger number and more
      varied types of wounds. METHODS: A systematic animal experiment was conducted to
      determine the effects of DGD on normal, non-injured skin, burns, exposed dermis
      of donor sites, and skin punch biopsy wells. Partial thickness dermal burns and
      partial thickness skin graft donor sites were created on a pig and treated with a
      4-h application of DGD or its control hydrating vehicle that does not have any
      activity except hydration. Punch biopsy samples were taken before and after
      treatment and microscopically assessed for evidence of tissue viability and its
      respective components thickness. RESULTS: Rapid dissolution of the burn eschar
      was noted in all DGD but not vehicle treated burns. There was no apparent damage
      to the underlying sub eschar dermis, donor sites, normal skin or punch biopsy
      wells after exposure to DGD. While the thickness of the treated tissues slightly
      increased due to edema, the increase in dermal thickness was similar after
      treatment with DGD or its vehicle. The increase in the cross section surface area
      of the treated punch biopsy wells was similar after treatment with DGD and its
      control vehicle. CONCLUSIONS: Exposure of the burn eschar to DGD results in its
      rapid dissolution. Exposure of normal skin or non-burned dermis to DGD has no
      effects demonstrating its selectivity to eschar.

PMID- 22385644
TI  - The role of self-determination theory and motivational interviewing in behavioral
      nutrition, physical activity, and health: an introduction to the IJBNPA special
      series.

PMID- 22385645
TI  - Bioenergetics at extreme temperature: Thermus thermophilus ba(3)- and caa(3)-type
      cytochrome c oxidases.
AB  - Seven years into the completion of the genome sequencing projects of the
      thermophilic bacterium Thermus thermophilus strains HB8 and HB27, many questions
      remain on its bioenergetic mechanisms. A key fact that is occasionally overlooked
      is that oxygen has a very limited solubility in water at high temperatures. The
      HB8 strain is a facultative anaerobe whereas its relative HB27 is strictly
      aerobic. This has been attributed to the absence of nitrate respiration genes
      from the HB27 genome that are carried on a mobilizable but highly-unstable
      plasmid. In T. thermophilus, the nitrate respiration complements the primary
      aerobic respiration. It is widely known that many organisms encode multiple
      biochemically-redundant components of the respiratory complexes. In this
      minireview, the presence of the two cytochrome c oxidases (CcO) in T.
      thermophilus, the ba(3)- and caa(3)-types, is outlined along with functional
      considerations. We argue for the distinct evolutionary histories of these two CcO
      including their respective genetic and molecular organizations, with the caa(3)
      oxidase subunits having been initially 'fused'. Coupled with sequence analysis,
      the ba(3)-oxidase crystal structure has provided evolutionary and functional
      information; for example, its subunit I is more closely related to archaeal
      sequences than bacterial and the substrate-enzyme interaction is hydrophobic as
      the elevated growth temperature weakens the electrostatic interactions common in
      mesophiles. Discussion on the role of cofactors in intra- and intermolecular
      electron transfer and proton pumping mechanism is also included.

PMID- 22385646
TI  - Resistance training, visceral obesity and inflammatory response: a review of the
      evidence.
AB  - Intra-abdominal obesity is an important risk factor for low-grade inflammation,
      which is associated with increased risk for diabetes mellitus and cardiovascular
      disease. For the most part, recommendations to treat or prevent overweight and
      obesity via physical activity have focused on aerobic endurance training as it is
      clear that aerobic training is associated with much greater energy expenditure
      during the exercise session than resistance training. However, due to the
      metabolic consequences of reduced muscle mass, it is understood that normal
      ageing and/or decreased physical activity may lead to a higher prevalence of
      metabolic disorders. Whether resistance training alters visceral fat and the
      levels of several pro-inflammatory cytokines produced in adipose tissue has not
      been addressed in earlier reviews. Because evidence suggests that resistance
      training may promote a negative energy balance and may change body fat
      distribution, it is possible that an increase in muscle mass after resistance
      training may be a key mediator leading to a better metabolic control. Considering
      the benefits of resistance training on visceral fat and inflammatory response, an
      important question is: how much resistance training is needed to confer such
      benefits? Therefore, the purpose of this review was to address the importance of
      resistance training on abdominal obesity, visceral fat and inflammatory response.

PMID- 22385647
TI  - Transmission dynamics and risk factors for pandemic H1N1-related illness:
      outbreak investigation in a rural community of British Columbia, Canada.
AB  - OBJECTIVE: To characterize the first-wave epidemiologic features of influenza
      like illness (ILI) associated with the novel pandemic A/H1N1 [A(H1N1)pdm09]
      virus. METHODS: We used generalized linear mixed models (GLMM) to assess risk
      factors and non-parametric and/or parametric distributions to estimate attack
      rates, secondary attack rates (SAR), duration of illness, and serial interval
      during a laboratory-confirmed community outbreak of A(H1N1)pdm09 clustered around
      on-reserve residents and households of an elementary school in rural British
      Columbia, Canada, in late April/early May 2009. ILI details were collected as
      part of outbreak investigation by community telephone survey in early June 2009.
      RESULTS: Overall, 92/408 (23%) of participants developed ILI and 36/408 (9%)
      experienced medically attended ILI (MAILI). The overall SAR in households was
      22%: highest among participants 1-4 years of age (yoa) (50%) followed by < 1 yoa
      (38%), 5-8 yoa (20%), 10-19 yoa (13%), 20-49 yoa (20%), and 50-64 yoa (0%). The
      median serial interval was estimated at 3.5 days (95% CI: 2.1-5.1). In
      multivariable GLMM analysis, having a chronic condition (OR: 2.58; 95% CI: 1.1
      6.04), younger age [1-8 yoa: OR: 4.63; 95% CI: 2.25-9.52; 9-19 yoa: OR: 1.95; 95%
      CI: 0.97-3.9 (referent: >= 20 yoa)] and receipt of 2008-2009 influenza vaccine
      (OR: 2.68; 95% CI: 1.37-5.25) were associated with increased risk of ILI. Median
      duration of illness was 9 days, longer among those with chronic conditions (21
      days). Median time to seeking care after developing illness was 4.5 days. On
      reserve participants had higher chronic conditions, household density, ILI,
      MAILI, and SAR. CONCLUSIONS: During a community outbreak of A(H1N1)pdm09-related
      illness, we identified substantial clinical ILI attack rates exceeding 20% with
      secondary household attack rates as high as 50% in young children. The serial
      interval was short suggesting a narrow period to prevent transmission.

PMID- 22385648
TI  - Where PI3K/Akt meets Smads: the crosstalk determines human embryonic stem cell
      fate.
AB  - Coordinated interactions between signaling networks govern the balance of cell
      fate decisions in human embryonic stem cells. In this issue, Singh et al. (2012)
      report that PI3K/Akt signaling switches Activin/Smad activity between pro-self
      renewal and prodifferentiation by regulating ERK and GSK3beta/beta-catenin
      signaling.

PMID- 22385649
TI  - Special stem cells for bone.
AB  - Mesenchymal stem cells (MSCs) are multipotential in vitro, but their endogenous
      properties are poorly defined. In this issue of Cell Stem Cell, Park et al.
      (2012) report that an MSC-like, osteolineage-directed Mx1+ population generates
      new osteoblasts at sites of bone damage, suggesting its potential for skeletal
      repair and regeneration.

PMID- 22385650
TI  - iPSCs to the rescue in Alzheimer's research.
AB  - A crucial limitation to our understanding of Alzheimer's disease has been the
      inability to test hypotheses on live, patient-specific neurons. A recent study in
      Nature by Israel et al. (2012) reports that iPSC-derived neurons from AD patients
      recapitulate multiple aspects of disease pathology.

PMID- 22385651
TI  - The long, the short, and the micro: a polyA tale of Pax3 in satellite cells.
AB  - The use of alternative polyadenylation sites is emerging as an important
      regulator of gene expression. In this issue of Cell Stem Cell, Boutet et al.
      (2012) report that alternative 3'UTRs of the Pax3 transcript restrict its
      expression to axial satellite cells through miR-mediated targeting of one of the
      isoforms.

PMID- 22385652
TI  - Egg sharing for research: a successful outcome for patients and researchers.

PMID- 22385653
TI  - Harnessing the mesenchymal stem cell secretome for the treatment of
      cardiovascular disease.
AB  - The broad repertoire of secreted trophic and immunomodulatory cytokines produced
      by mesenchymal stem cells (MSCs), generally referred to as the MSC secretome, has
      considerable potential for the treatment of cardiovascular disease. However,
      harnessing this MSC secretome for meaningful therapeutic outcomes is challenging
      due to the limited control of cytokine production following their
      transplantation. This review outlines the current understanding of the MSC
      secretome as a therapeutic for treatment of ischemic heart disease. We discuss
      ongoing investigative directions aimed at improving cellular activity and
      characterizing the secretome and its regulation in greater detail. Finally, we
      provide insights on and perspectives for future development of the MSC secretome
      as a therapeutic tool.

PMID- 22385654
TI  - Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone
      maintenance and regeneration.
AB  - Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered
      clinical application despite little definition of their function in residence.
      Here, we report genetic pulse-chase experiments that define osteoblastic cells as
      short-lived and nonreplicative, requiring replenishment from bone-marrow-derived,
      Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress
      and migrate to sites of injury, supplying new osteoblasts during fracture
      healing. Single cell transplantation yielded progeny that both preserve
      progenitor function and differentiate into osteoblasts, producing new bone. They
      are capable of local and systemic translocation and serial transplantation. While
      these cells meet current definitions of MSCs in vitro, they are osteolineage
      restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived
      MSCs may be a heterogeneous population with the Mx1(+) population, representing a
      highly dynamic and stress responsive stem/progenitor cell population of fate
      restricted potential that feeds the high cell replacement demands of the adult
      skeleton.

PMID- 22385655
TI  - Hematopoietic stem cell subtypes expand differentially during development and
      display distinct lymphopoietic programs.
AB  - Adult hematopoietic stem cells (HSCs) with serially transplantable activity
      comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid
      cells; the other appears selectively lymphoid deficient. We now show that both of
      these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the
      rarer, lymphoid-deficient HSCs immediately gaining an increased representation in
      the fetal bone marrow, suggesting that the marrow niche plays a key role in
      regulating their ensuing preferential amplification. Clonal analysis of HSC
      expansion posttransplant showed that both subtypes display an extensive but
      variable self-renewal activity with occasional interconversion. Clonal analysis
      of their differentiation programs demonstrated functional and molecular as well
      as quantitative HSC subtype-specific differences in the lymphoid progenitors they
      generate but an indistinguishable production of multipotent and myeloid
      restricted progenitors. These findings establish a level of heterogeneity in HSC
      differentiation and expansion control that may have relevance to stem cell
      populations in other hierarchically organized tissues.

PMID- 22385656
TI  - Functional antagonism between Sall4 and Plzf defines germline progenitors.
AB  - Transcription factors required for formation of embryonic tissues often maintain
      their expression in adult stem cell populations, but whether their function
      remains equivalent is not clear. Here we demonstrate critical and distinct roles
      for Sall4 in development of embryonic germ cells and differentiation of postnatal
      spermatogonial progenitor cells (SPCs). In differentiating SPCs, Sall4 levels
      transiently increase and Sall4 physically interacts with Plzf, a transcription
      factor exclusively required for adult stem cell maintenance. Mechanistically,
      Sall4 sequesters Plzf to noncognate chromatin domains to induce expression of
      Kit, a target of Plzf-mediated repression required for differentiation. Plzf in
      turn antagonizes Sall4 function by displacing Sall4 from cognate chromatin to
      induce Sall1 expression. Taken together, these data suggest that transcription
      factors required for embryonic tissue development postnatally take on distinct
      roles through interaction with opposing factors, which hence define properties of
      the adult stem cell compartment.

PMID- 22385657
TI  - Genetic regulators of a pluripotent adult stem cell system in planarians
      identified by RNAi and clonal analysis.
AB  - Pluripotency is a central, well-studied feature of embryonic development, but the
      role of pluripotent cell regulation in somatic tissue regeneration remains poorly
      understood. In planarians, regeneration of entire animals from tissue fragments
      is promoted by the activity of adult pluripotent stem cells (cNeoblasts). We
      utilized transcriptional profiling to identify planarian genes expressed in adult
      proliferating, regenerative cells (neoblasts). We also developed quantitative
      clonal analysis methods for expansion and differentiation of cNeoblast
      descendants that, together with RNAi, revealed gene roles in stem cell biology.
      Genes encoding two zinc finger proteins, Vasa, a LIM domain protein, Sox and Jun
      like transcription factors, two candidate RNA-binding proteins, a Setd8-like
      protein, and PRC2 (Polycomb) were required for proliferative expansion and/or
      differentiation of cNeoblast-derived clones. These findings suggest that
      planarian stem cells utilize molecular mechanisms found in germ cells and other
      pluripotent cell types and identify genetic regulators of the planarian stem cell
      system.

PMID- 22385658
TI  - Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated
      switch that controls the balance between self-renewal and differentiation.
AB  - A general mechanism for how intracellular signaling pathways in human pluripotent
      cells are coordinated and how they maintain self-renewal remain to be elucidated.
      In this report, we describe a signaling mechanism where PI3K/Akt activity
      maintains self-renewal by restraining prodifferentiation signaling through
      suppression of the Raf/Mek/Erk and canonical Wnt signaling pathways. When active,
      PI3K/Akt establishes conditions where Activin A/Smad2,3 performs a pro-self
      renewal function by activating target genes, including Nanog. When PI3K/Akt
      signaling is low, Wnt effectors are activated and function in conjunction with
      Smad2,3 to promote differentiation. The switch in Smad2,3 activity after
      inactivation of PI3K/Akt requires the activation of canonical Wnt signaling by
      Erk, which targets Gsk3beta. In sum, we define a signaling framework that
      converges on Smad2,3 and determines its ability to regulate the balance between
      alternative cell states. This signaling paradigm has far-reaching implications
      for cell fate decisions during early embryonic development.

PMID- 22385659
TI  - Alternative polyadenylation mediates microRNA regulation of muscle stem cell
      function.
AB  - Pax3, a key myogenic regulator, is transiently expressed during activation of
      adult muscle stem cells, or satellite cells (SCs), and is also expressed in a
      subset of quiescent SCs (QSCs), but only in specific muscles. The mechanisms
      regulating these variations in expression are not well understood. Here we show
      that Pax3 levels are regulated by miR-206, a miRNA with a previously demonstrated
      role in myogenic differentiation. In most QSCs and activated SCs, miR-206
      expression suppresses Pax3 expression. Paradoxically, QSCs that express high
      levels of Pax3 also express high levels of miR-206. In these QSCs, Pax3
      transcripts are subject to alternative polyadenylation, resulting in transcripts
      with shorter 3' untranslated regions (3'UTRs) that render them resistant to
      regulation by miR-206. Similar alternate polyadenylation of the Pax3 transcript
      also occurs in myogenic progenitors during development. Our findings may reflect
      a general role of alternative polyadenylation in circumventing miRNA-mediated
      regulation of stem cell function.

PMID- 22385660
TI  - Low incidence of DNA sequence variation in human induced pluripotent stem cells
      generated by nonintegrating plasmid expression.
AB  - The utility of induced pluripotent stem cells (iPSCs) as models to study diseases
      and as sources for cell therapy depends on the integrity of their genomes.
      Despite recent publications of DNA sequence variations in the iPSCs, the true
      scope of such changes for the entire genome is not clear. Here we report the
      whole-genome sequencing of three human iPSC lines derived from two cell types of
      an adult donor by episomal vectors. The vector sequence was undetectable in the
      deeply sequenced iPSC lines. We identified 1,058-1,808 heterozygous single
      nucleotide variants (SNVs), but no copy-number variants, in each iPSC line. Six
      to twelve of these SNVs were within coding regions in each iPSC line, but ~50% of
      them are synonymous changes and the remaining are not selectively enriched for
      known genes associated with cancers. Our data thus suggest that episome-mediated
      reprogramming is not inherently mutagenic during integration-free iPSC induction.

PMID- 22385662
TI  - Quintuplets: a rare event following clomiphene citrate therapy.

PMID- 22385663
TI  - Informed (but independent) choice.

PMID- 22385661
TI  - Emotion regulation and impulsivity in young adults.
AB  - Past research has linked both emotion regulation and impulsivity with the
      development and maintenance of addictions. However, no research has investigated
      the relationship between emotion regulation and impulsivity within young adults.
      In the present study, we analyzed 194 young adults (27.8% female; 21.3 +/- 3.32
      years old; 91.8% single; 85.1% Caucasian), grouping them as low, average, or high
      emotionally dysregulated, and compared self-reported impulsivity, impulsive
      behaviors (such as alcohol and substance use and gambling) and cognitive
      impulsivity. We hypothesized that those with high levels of emotion dysregulation
      would score higher on self-reported and cognitive impulsivity, and report more
      impulsive behaviors. Analysis indicated that compared to low, the high emotion
      dysregulation group scored significantly higher on two self-report measures of
      impulsivity, harm avoidance, and cognitive reasoning. No significant differences
      were found between groups in impulsive behaviors and cognitive impulsivity.
      Overall, this study highlights the relationship between emotion dysregulation and
      impulsivity, suggesting that emotion regulation may be an important factor to
      consider when assessing individuals at a higher risk for developing an addiction.

PMID- 22385664
TI  - Group prenatal care versus individual prenatal care: a systematic review and meta
      analyses.
AB  - OBJECTIVE: To compare the effects of group prenatal care (GPC) and individual
      prenatal care (IPC) on perinatal health outcomes, including our primary outcomes
      of preterm birth (PTB < 37 weeks) and low birth weight (< 2500 g). DATA SOURCES:
      We searched Medline, Embase, CINAHL, and the references of selected articles.
      STUDY SELECTION: Two reviewers independently performed each step of the
      systematic review. Of the 4178 non-duplicate titles and abstracts identified, 77
      were selected for full-text review. An additional eight full-text articles were
      selected from reference lists. Overall, 85 full-text articles were reviewed.
      Studies included assessed maternal or infant health outcomes. DATA EXTRACTION AND
      DATA SYNTHESIS: Two reviewers independently extracted data from eligible full
      text articles. Statistical analyses were completed using Review Manager, version
      5.0 (Copenhagen: The Nordic Cochrane Centre, Cochrane Collaboration, 2011),
      whereby dichotomous variables and continuous outcomes were analyzed using
      relative risk and mean difference, respectively. The random effects model was
      employed to pool data. Where available, adjusted data were used to assess the
      independent effect of GPC. Eight studies of mostly low quality (three randomized
      controlled trials and five cohort studies) were included, involving 3242 women,
      most at high risk. Women randomized to GPC had lower rates of PTB (RR 0.71; 95%
      CI 0.52 to 0.96), no difference in rates of LBW (RR 0.91; 95% CI 0.65 to 1.27) or
      IUGR (RR 0.85; 95% CI 0.61 to 1.19), fewer Caesarean sections (RR 0.80; 95% CI
      0.67 to 0.93), and slightly higher rates of breastfeeding (RR 1.08; 95% CI 1.02
      to 1.14). CONCLUSION: Studies comparing GPC with IPC are mostly of low quality
      and in high-risk groups, although two randomized studies, one a secondary
      analysis, showed improvement in some outcomes, including rates of PTB in women
      participating in GPC. In order to determine generalizability, more high-quality
      studies of GPC are needed.

PMID- 22385665
TI  - Choice of antibiotic for group B streptococcus in women in labour based on
      antibiotic sensitivity testing.
AB  - OBJECTIVE: To determine whether pregnant women testing positive for Group B
      Streptococcus (GBS) are receiving appropriate antibiotic prophylaxis in labour
      based on sensitivity testing. METHODS: We performed a retrospective chart review
      of all women who delivered at our institution from January 1 to December 31,
      2008. We identified all GBS-positive women, and then abstracted data regarding
      demographic characteristics, method of GBS detection (recto-vaginal or urine
      culture), prevalence, and antibiotic use. The main outcome measure was the
      proportion of GBS-positive women who were managed appropriately. RESULTS: During
      the study period 628 (22%) of 2878 women were identified as having GBS-positive
      cultures. Sensitivity testing was available for 481 of the recto-vaginal
      cultures. All were sensitive to penicillin. The rates of resistance for recto
      vaginal culture were 22% for erythromycin, 19% for clindamycin, and 18% for both.
      Four hundred eighty-one women (93%) were treated with penicillin, 30 (6%) with
      clindamycin, three with cefazolin, and two with vancomycin. One hundred nine
      women (17%) who were GBS-positive did not receive antibiotics. Forty-four women
      (9%) did not receive appropriate antibiotic prophylaxis based on sensitivity
      testing. CONCLUSION: Most GBS-positive women at our institution received an
      appropriate antibiotic during labour based on sensitivity testing. Our population
      reflects the Canadian GBS-positivity rate, which is similar to those observed in
      published studies from other populations. Future work should focus on developing
      strategies that re-emphasize GBS testing and treatment guidelines for prenatal
      care providers and on systems to ensure GBS-positive women are given the
      appropriate antibiotics during labour.

PMID- 22385666
TI  - Impact of the creation of a specialized clinic for prenatal blood sampling and
      follow-up care in pregnant women.
AB  - OBJECTIVE: To evaluate (1) the effect on gestational diabetes mellitus (GDM)
      screening rates of having a specialized clinic for pregnant women offering blood
      sampling and screening for GDM, and (2) the impact on perinatal outcomes of
      having early GDM screening and follow-up provided by the specialized clinic.
      METHODS: We performed a retrospective cohort study, based on electronic health
      records. We compared data from women who delivered during a period when the Blood
      Sampling in Pregnancy (BSP) clinic was operating (2008-2009; n = 2780) to a time
      period before the clinic was established (2006-2007; n = 2591). During the 2008
      2009 period, we compared data from women who had GDM screening in the first
      trimester with women who had screening during the second trimester and with women
      who were not screened. RESULTS: Following the creation of the BSP clinic, overall
      GDM screening rates reached 72.4% in 2008-2009, compared with 48.9% in 2006-2007
      (P < 0.001) and GDM screening was more likely to be performed in the first
      trimester (36.7% vs. 0.4%; P < 0.001). During the period when the BSP clinic was
      operating (2008-2009), women who had GDM screening in the first trimester had
      lower rates of Caesarean section (15.7% vs. 22.1%; P < 0.001) and neonatal
      complications (bradycardia: 3.6% vs. 6.8%; P = 0.003; respiratory distress: 9.6%
      vs. 13.2%; P = 0.02; and admission to NICU: 15.4% vs. 26.8%; P < 0.001) than
      women who did not perform GDM screening. CONCLUSION: In our population, creation
      of a clinic offering specialized care to pregnant women improved GDM screening
      rates. With the support of the BSP clinic, women who had early GDM screening were
      less likely to undergo Caesarean section and their offspring had fewer perinatal
      complications.

PMID- 22385667
TI  - A Canadian urban early pregnancy assessment clinic: a review of the first year of
      operation.
AB  - OBJECTIVE: To review the services provided by an early pregnancy assessment
      clinic (EPAC) in Vancouver, British Columbia, and to assess the characteristics
      of the women accessing their services and their satisfaction with the care
      provided. METHODS: The EPAC at BC Women's Hospital and Health Centre was opened
      in September 2007 to offer assessment of early pregnancy complications and
      management of early pregnancy loss. We conducted a review of the records of all
      patients who accessed the clinic in its first year of operation to review the
      origin of referrals, patient assessments, diagnoses, treatment, complications,
      and follow-up. Additionally, we distributed satisfaction surveys to patients.
      RESULTS: A total of 411 patients were referred to the EPAC in its first year of
      operation. Most referrals were from family physicians (38%), and the primary
      reason for referral was most commonly cramping and/or spotting (57%). The mean
      wait time for patients to be seen was 2.02 working days, and the majority of
      women (91%) were given a diagnosis at their first clinic visit. After assessment,
      48% of women had manual vacuum aspiration or dilatation and curettage arranged,
      21% had expectant management, and 17% required no treatment, because of complete
      miscarriage. While 94% of patients with non-viable pregnancies were treated at
      EPAC, 6% were referred to other health care agencies. In the satisfaction surveys
      completed, comments about the EPAC were largely positive and primarily focused on
      the emotional support and level of care received. CONCLUSION: In its first year
      of operation, the EPAC was well used and provided efficient and compassionate
      care. Patients reported high satisfaction with the quality of care received from
      staff, and showed particular appreciation for the emotional care received.

PMID- 22385668
TI  - Oocyte cryopreservation in Canada: a survey of Canadian ART clinics.
AB  - OBJECTIVE: To determine the status of oocyte cryopreservation in Canadian
      assisted reproductive technology (ART) clinics. METHODS: An online survey was
      sent to the medical directors of all Canadian ART clinics between December 2010
      and February 2011. The survey included questions about the availability of, the
      indications for, and the elements of consent for oocyte cryopreservation. Clinics
      were also asked whether they offered social egg freezing. RESULTS: Twenty of the
      28 Canadian ART clinics (71.4%) participated in this survey, and 16 (80%) of
      those clinics offered oocyte cryopreservation. Forty-five percent of the clinics
      offered elective oocyte cryopreservation (social egg freezing) for healthy women
      seeking to prolong fertility. Although most clinics counselled patients that
      oocyte cryopreservation is experimental, most clinics (87.5%) did not perform the
      procedure under a protocol approved by a research ethics board. The majority of
      clinics included most of the essential elements of informed consent during their
      counselling process. Most clinics that offered social egg freezing performed the
      procedure for women up to the age of 42, although some clinics did not offer the
      procedure for women under the age of 35 (28.6%) or over the age of 38 (42.9%).
      CONCLUSION: More than one half of Canadian ART clinics are offering oocyte
      cryopreservation, although not all clinics offer social egg freezing for healthy
      women to prolong fertility. Most clinics described the technique as experimental,
      and the majority included most of the elements of informed consent in their
      counselling process.

PMID- 22385669
TI  - A national survey of endoscopic practice among gynaecologists in Canada.
AB  - OBJECTIVE: To assess the current status of endoscopic gynaecological surgery in
      Canada, as well as the attitudes, perceptions, and educational preferences
      regarding endoscopy among Canadian obstetrician-gynaecologists. METHODS: An
      electronic online survey was sent to 630 obstetrician-gynaecologists in Canada
      through the Society of Obstetricians and Gynaecologists of Canada electronic
      mailing list. Survey respondents were asked about demographic variables, level of
      training and current practice of endoscopic procedures, reasons for and barriers
      to performing endoscopy, and interest in continuing surgical education in
      laparoscopy and hysteroscopy. RESULTS: A total of 178 responses (28.3%) were
      collected and 152 (85.4%) analyzed. The majority of respondents were general
      obstetrician-gynaecologists (78.0%). More gynaecologic surgeons performed
      abdominal (92.7%) and vaginal hysterectomies (89.7%) than laparoscopic (68.4%)
      and robotic hysterectomies (2.2%). Even though 93.2% of respondents selected the
      endoscopic approach as the preferred approach to surgery for their patients,
      38.7% of respondents did not feel that they had adequate training during
      residency to perform endoscopy. Lack of operating room resources and lack of time
      and opportunity for further training were frequently selected as major barriers
      to performing endoscopy. Participants identified weekend continuing medical
      education courses and trained endoscopic surgeon outreach as preferred methods of
      acquiring endoscopic skills. CONCLUSION: This survey provides a contemporary
      assessment of the current endoscopic practice patterns of Canadian obstetrician
      gynaecologists, and it helps to identify some potentially modifiable factors
      hindering the practice of endoscopy and some possible solutions to overcoming
      these barriers.

PMID- 22385670
TI  - Can online learning adequately prepare medical students to undertake a first
      female pelvic examination?
AB  - OBJECTIVE: To determine whether a novel web-based learning module could
      adequately prepare first-year undergraduate medical students to skilfully perform
      their first female pelvic examination. METHODS: First-year Queen's University
      medical students without prior training or experience in female pelvic
      examination were recruited for this study. After viewing key segments of the
      learning module, students were evaluated while performing a pelvic examination on
      a female volunteer using a standardized assessment checklist (total score = 30
      points). Descriptive and comparative statistics were generated. RESULTS: Forty
      five students participated with a mean age of 24 years (range 20 to 40). The mean
      score (+/-SD) on the assessment checklist was 23.9 +/- 3.6 points, (range 17 to
      30). All study participants received a passing grade of >= 50% (15/30 points),
      and 53.3% (24/45) received an honours grade of >= 80% (24/30 points). Of the
      participants, 88.9% (40/45) agreed that they were well prepared for their first
      female pelvic examination after viewing the training video. Mean scores were
      similar for male students (23.9, n = 22) and female students (23.8, n = 23) (P =
      0.90, t test). Mean scores were not higher in those who watched key segments of
      the learning module more than once. CONCLUSION: This learning module viewed
      immediately prior to a simulated clinic session afforded first-year medical
      students the necessary knowledge and skills to perform a first female pelvic
      examination. This was accomplished with as little as one viewing, and could lead
      to savings in organizational costs and instruction time for medical school
      curricula.

PMID- 22385671
TI  - Information-sharing to promote informed choice in prenatal screening in the
      spirit of the SOGC clinical practice guideline: a proposal for an alternative
      model.
AB  - The 2011 SOGC clinical practice guideline "Prenatal Screening for Fetal
      Aneuploidy in Singleton Pregnancies" recommends that clinicians offer prenatal
      screening to all pregnant women and provide counselling in a non-directive
      manner. Non-directive counselling is intended to facilitate autonomous decision
      making and remove the clinician's views regarding a particular course of action.
      However, recent research in genetic counselling raises concerns that non
      directive counselling is neither possible nor desirable, and that it may not be
      the best way to facilitate informed choice. We propose an alternative model of
      information-sharing specific to prenatal screening that combines attributes of
      the models of informative decision-making and shared decision-making. Our
      proposed model is intended to provide clinicians with a strategy to communicate
      information about prenatal screening in a way that facilitates a shared
      deliberative process and autonomous decision-making. Our proposed model may
      better prepare a pregnant woman to make an informed choice about participating in
      prenatal screening on the basis of her consideration of the medical information
      provided by her clinician and her particular circumstances and values.

PMID- 22385672
TI  - Genetic considerations for a woman's annual gynaecological examination.
AB  - OBJECTIVE: To provide the physician with an overview of common genetic conditions
      that should be considered during a women's annual gynaecological assessment to
      determine the patient's risk or to initiate specific testing or referral to
      another subspecialty service, depending on personal or family history. OPTIONS:
      This genetic information can be used for patient education and possible disease
      and/or mutation screening or diagnosis. OUTCOMES: The use of this genetic
      information may allow improved risk-benefit assessment and management at the
      annual gynaecological examination. EVIDENCE: Studies published in English up to
      and including May 2010 were retrieved through searches of PubMed and the Cochrane
      Library, using appropriate controlled vocabulary (gynaecological diagnosis,
      genetic inheritance) and key words (genetic risk, genetic mutation, inheritance,
      family history, uterus, ovary, endometrial, vagina, colon, gastric, renal,
      breast, cardiac, thrombophilia, diabetes, epilepsy, leiomyomata uteri). Other
      literature sources were identified through searching the web sites of health
      technology assessment and health technology assessment-related agencies, clinical
      practice guideline collections, clinical trial registries, and national and
      international medical specialty societies. VALUES: The levels of evidence are not
      adequate for evidence-based recommendations to be made. BENEFITS, HARMS, AND
      COSTS: This committee opinion will enhance the use of new genetic knowledge and
      its application to the annual gynaecological care of women. Risk management and
      diagnostic opportunities for genetic gynaecological conditions will be improved.
      A more complete understanding of genetic conditions may increase anxiety and
      psychological stress for women and their families. SPONSORS: Society of
      Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS: The levels of
      evidence are not adequate for evidence-based recommendations to be made.

PMID- 22385673
TI  - Management of varicella infection (chickenpox) in pregnancy.
AB  - OBJECTIVE: To review the existing data regarding varicella zoster virus infection
      (chickenpox) in pregnancy, interventions to reduce maternal complications and
      fetal infection, and antepartum and peripartum management. METHODS: The maternal
      and fetal outcomes in varicella zoster infection were reviewed, as well as the
      benefit of the different treatment modalities in altering maternal and fetal
      sequelae. EVIDENCE: Medline was searched for articles and clinical guidelines
      published in English between January 1970 and November 2010. VALUES: The quality
      of evidence was rated using the criteria described in the Report of the Canadian
      Task Force on Preventive Health Care. Recommendations for practice were ranked
      according to the method described in that report (Table). RECOMMENDATIONS: 1.
      Varicella immunization is recommended for all non-immune women as part of pre
      pregnancy and postpartum care. (II-3B) 2. Varicella vaccination should not be
      administered in pregnancy. However, termination of pregnancy should not be
      advised because of inadvertent vaccination during pregnancy. (II-3D) 3. The
      antenatal varicella immunity status of all pregnant women should be documented by
      history of previous infection, varicella vaccination, or varicella zoster
      immunoglobulin G serology. (III-C) 4. All non-immune pregnant women should be
      informed of the risk of varicella infection to themselves and their fetuses. They
      should be instructed to seek medical help following any contact with a person who
      may have been contagious. (II-3B) 5. In the case of a possible exposure to
      varicella in a pregnant woman with unknown immune status, serum testing should be
      performed. If the serum results are negative or unavailable within 96 hours from
      exposure, varicella zoster immunoglobulin should be administered. (III-C) 6.
      Women who develop varicella infection in pregnancy need to be made aware of the
      potential adverse maternal and fetal sequelae, the risk of transmission to the
      fetus, and the options available for prenatal diagnosis. (II-3C) 7. Detailed
      ultrasound and appropriate follow-up is recommended for all women who develop
      varicella in pregnancy to screen for fetal consequences of infection. (III-B) 8.
      Women with significant (e.g., pneumonitis) varicella infection in pregnancy
      should be treated with oral antiviral agents (e.g., acyclovir 800 mg 5 times
      daily). In cases of progression to varicella pneumonitis, maternal admission to
      hospital should be seriously considered. Intravenous acyclovir can be considered
      for severe complications in pregnancy (oral forms have poor bioavailability). The
      dose is usually 10 to 15 mg/kg of BW or 500 mg/m2 IV every 8 h for 5 to 10 days
      for varicella pneumonitis, and it should be started within 24 to 72 h of the
      onset of rash. (III-C) 9. Neonatal health care providers should be informed of
      peripartum varicella exposure in order to optimize early neonatal care with
      varicella zoster immunoglobulin and immunization. (III-C) Varicella zoster
      immunoglobulin should be administered to neonates whenever the onset of maternal
      disease is between 5 days before and 2 days after delivery. (III-C).

PMID- 22385674
TI  - Design, synthesis, in vitro antimicrobial and anticancer activity of novel
      methylenebis-isoxazolo[4,5-b]azepines derivatives.
AB  - A series of novel methylene bis-isoxazolo[4,5-b]azepines have been synthesized by
      reaction of 3,5-dimethyl-4-nitroisoxazole 6 with an appropriate methylene bis
      chalcones 7 to obtain various Michael adducts 8a-i, which on treatment with
      SnCl(2)-MeOH underwent reductive cyclization to afford the title compounds 9a-i.
      Structure of these compounds were established on the basis of IR, (1)H NMR, (13)C
      NMR and mass spectral data. The title compounds 9a-i were evaluated for their in
      vitro antimicrobial and anticancer activities. Compounds 9h and 9i exhibited
      potent antimicrobial and anticancer activities as that of standard drugs.

PMID- 22385675
TI  - Novel molecular combination deriving from natural aminoacids and polyphenols:
      Design, synthesis and free-radical scavenging activities.
AB  - Following the recent output of scientific publications in the matter of synergic
      activity between different antioxidants, we have undertaken the present study
      with the aim to synthesize new molecules with radical-scavengers activity based
      on the conjugation of bioactive portions (i.e. phenols, cysteine, methionine or
      tyrosine), characterized by different structures and mechanisms of action, to
      promote the simultaneous quenching of different radical species in the site of
      the oxidative damage. In this context, derivatives of phenolic acid, aminoacids
      and dopamine have been also prepared. The newly synthesized compounds were
      evaluated in vitro applying specific and complementary antioxidant test such as
      DPPH assay and ORAC test. As emerged from the evaluation, prerequisites for the
      activity of the synthesized molecules were: i) the maintenance of at least two
      hydroxylic groups on the aromatic moiety of phenolic portion, ii) the presence of
      a spacer between the aromatic moiety and the carbonilic group.

PMID- 22385676
TI  - Self-determination theory: its application to health behavior and complementarity
      with motivational interviewing.
AB  - Mounting evidence implicates health behaviors (e.g., nutrition, physical
      activity, tobacco abstinence) in various health outcomes. As the science of
      behavior change has emerged, increasing emphasis has been placed on the use of
      theory in developing and testing interventions. Self-determination theory (SDT)-a
      theoretical perspective-and motivational interviewing (MI)-a set of clinical
      techniques-have both been used in health behavior intervention contexts. Although
      developed for somewhat different purposes and in relatively different domains,
      there is a good deal of conceptual overlap between SDT and MI. Accordingly, SDT
      may offer the theoretical backing that historically has been missing from MI, and
      MI may offer SDT some specific direction with respect to particular clinical
      techniques that have not been fully borne out within the confines of health
      related applications of SDT. Research is needed to empirically test the overlap
      and distinctions between SDT and MI and to determine the extent to which these
      two perspectives can be combined or co-exist as somewhat distinct approaches.

PMID- 22385677
TI  - Clinical significance of SOX9 in human non-small cell lung cancer progression and
      overall patient survival.
AB  - BACKGROUND: Sex determining region Y (SRY)-related high mobility groupbox 9
      (SOX9) is an important transcription factor required for development, which
      regulates the expression of target genes in the associated pathway. The aim of
      this study was to describe the expression of SOX9 in human non-small cell lung
      cancer (NSCLC) and to investigate the association between SOX9 expression and
      progression of NSCLC. METHODS: SOX9 protein and mRNA expression in normal human
      pneumonocytes, lung cancer cell lines, and eight pairs of matched lung cancer
      tissues and their adjacent normal lung tissues were detected by Western blotting
      and real-time reverse transcription-polymerase chain reaction (RT-PCR).
      Immunohistochemistry was used to determine SOX9 protein expression in 142 cases
      of histologically characterized NSCLC. Statistical analyses were applied to test
      for prognostic and diagnostic associations. RESULTS: SOX9 in lung cancer cell
      lines was upregulated at both mRNA and protein levels, and SOX9 mRNA and protein
      were also elevated in NSCLC tissues compared with levels in corresponding
      adjacent non-cancerous lung tissues. Immunohistochemical analysis demonstrated a
      high expression of SOX9 in 74/142 (52.1%) paraffin-embedded archival lung cancer
      biopsies. Statistical analysis indicated that upregulation of SOX9 was
      significantly correlated with the histological stage of NSCLC (P=0.017) and that
      patients with a high SOX9 level exhibited a shorter survival time (P<0.001).
      Multivariate analysis illustrated that SOX9 upregulation might be an independent
      prognostic indicator for the survival of patients with NSCLC. CONCLUSIONS: This
      work shows that SOX9 may serve as a novel and prognostic marker for NSCLC, and
      play a role during the development and progression of the disease.

PMID- 22385678
TI  - A bacterial reporter panel for the detection and classification of antibiotic
      substances.
AB  - The ever-growing use of pharmaceutical compounds, including antibacterial
      substances, poses a substantial pollution load on the environment. Such compounds
      can compromise water quality, contaminate soils, livestock and crops, enhance
      resistance of microorganisms to antibiotic substances, and hamper human health.
      We report the construction of a novel panel of genetically engineered Escherichia
      coli reporter strains for the detection and classification of antibiotic
      substances. Each of these strains harbours a plasmid that carries a fusion of a
      selected gene promoter to bioluminescence (luxCDABE) reporter genes and an
      alternative tryptophan auxotrophy-based non-antibiotic selection system. The
      bioreporter panel was tested for sensitivity and responsiveness to diverse
      antibiotic substances by monitoring bioluminescence as a function of time and of
      antibiotic concentrations. All of the tested antibiotics were detected by the
      panel, which displayed different response patterns for each substance. These
      unique responses were analysed by several algorithms that enabled clustering the
      compounds according to their functional properties, and allowed the
      classification of unknown antibiotic substances with a high degree of accuracy
      and confidence.

PMID- 22385679
TI  - Voxelwise meta-analysis of gray matter anomalies in Alzheimer's disease and mild
      cognitive impairment using anatomic likelihood estimation.
AB  - BACKGROUND: Many voxel-based morphometry studies in Alzheimer's disease (AD) and
      mild cognitive impairment (MCI) yielded not entirely consistent results. We
      conducted meta-analyses of gray matter anomalies to identify robust
      neuroanatomical changes between them. METHODS: A systematic review of voxel-based
      morphometry studies of patients with AD and MCI relative to healthy comparison
      subjects in PubMed, Embase databases from January 1995 to 29 April, 2011 was
      conducted. The anatomical distribution of the coordinates of gray matter
      differences was meta-analyzed using anatomical likelihood estimation (ALE).
      Separate maps of gray matter changes were constructed, and subtraction meta
      analysis between AD and MCI was also performed. RESULTS: Thirty-five AD studies
      and twenty-four MCI studies were included in the meta-analysis. Extensive gray
      matter deficits were present in the medial temporal lobe (including entorhinal
      cortex, hippocampus, parahippocampus, amygdala and uncus), thalamus, temporal,
      parietal, frontal and cingulate and insular cortices in AD. In MCI, gray matter
      reductions were identified in the medial temporal lobe (including entorhinal
      cortex, hippocampus, parahippocampus, amygdala and uncus), temporal, thalamus,
      and cingulate cortex. Subtraction meta-analysis found more severe gray matter
      deficit mainly in the left medial lobe (including parahippocampus, amygdala and
      hippocampus). CONCLUSIONS: Our meta-analysis identified similar distributions of
      neuroanatomical changes in AD and MCI, which are consistent with the hierarchical
      model of neuropathological alterations of neurofibrillary tangles in AD and MCI.
      Subtraction analysis provided evidence that the left MTL may be a neuroanatomical
      marker to evaluate disease progression from MCI to AD.

PMID- 22385680
TI  - Thiamine and Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common form of neurodegeneration in
      the elderly population. PD is clinically characterized by tremors, rigidity,
      slowness of movement and postural imbalance. A significant association has been
      demonstrated between PD and low levels of thiamine in the serum, which suggests
      that elevated thiamine levels might provide protection against PD. Genetic
      studies have helped identify a number of factors that link thiamine to PD
      pathology, including the DJ-1 gene, excitatory amino acid transporters (EAATs),
      the alpha-ketoglutarate dehydrogenase complex (KGDHC), coenzyme Q10 (CoQ10 or
      ubiquinone), lipoamide dehydrogenase (LAD), chromosome 7, transcription factor
      p53, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), and poly(ADP
      ribose) polymerase-1 gene (PARP-1). Thiamine has also been implicated in PD
      through its effects on L-type voltage-sensitive calcium channels (L-VSCC), matrix
      metalloproteinases (MMPs), prostaglandins (PGs), cyclooxygenase-2 (COX-2),
      reactive oxygen species (ROS), and nitric oxide synthase (NOS). Recent studies
      highlight a possible relationship between thiamine and PD. Genetic studies
      provide opportunities to determine which proteins may link thiamine to PD
      pathology. Thiamine can also act through a number of non-genomic mechanisms that
      include protein expression, oxidative stress, inflammation, and cellular
      metabolism. Further studies are needed to determine the benefits of using
      thiamine as a treatment for PD.

PMID- 22385681
TI  - Chronic fatigue syndrome: treatment without a cause.

PMID- 22385682
TI  - Why celebrate Joseph Lister?

PMID- 22385683
TI  - Effectiveness of internet-based cognitive behavioural treatment for adolescents
      with chronic fatigue syndrome (FITNET): a randomised controlled trial.
AB  - BACKGROUND: Chronic fatigue syndrome is characterised by persistent fatigue and
      severe disability. Cognitive behavioural therapy seems to be a promising
      treatment, but its availability is restricted. We developed Fatigue In Teenagers
      on the interNET (FITNET), the first dedicated internet-based therapeutic program
      for adolescents with this disorder, and compared its effectiveness with that of
      usual care. METHODS: Adolescents aged 12-18 years with chronic fatigue syndrome
      were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment
      centre in the Netherlands by use of a computer-generated blocked randomisation
      allocation schedule. The study was open label. Primary outcomes were school
      attendance, fatigue severity, and physical functioning, and were assessed at 6
      months with computerised questionnaires. Analysis was by intention to treat.
      Thereafter, all patients were offered FITNET if needed. This trial is registered,
      number ISRCTN59878666. FINDINGS: 68 of 135 adolescents were assigned to FITNET
      and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was
      significantly more effective than was usual care for all dichotomised primary
      outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk
      4.8, 95% CI 2.7-8.9; p<0.0001), absence of severe fatigue (57 [85%] vs 17 [27%],
      3.2, 2.1-4.9; p<0.0001), and normal physical functioning (52 [78%] vs 13 [20%],
      3.8, 2.3-6.3; p<0.0001). No serious adverse events were reported. INTERPRETATION:
      FITNET offers a readily accessible and highly effective treatment for adolescents
      with chronic fatigue syndrome. The results of this study justify implementation
      on a broader scale. FUNDING: Netherlands Organisation for Health Research and
      Development.

PMID- 22385684
TI  - [Skin manifestations of new targeted treatments].
AB  - Many cutaneous adverse events have been identified with recently developed
      targeted treatments. Some of them are common and specific, like paradoxical
      psoriasiform eruptions with anti-TNFalpha, papulopustular eruptions and
      paronychias with EGFR inhibitors and peculiar hand-foot skin reactions with
      multitargeted kinase inhibitors sorefenib and sunitinib. Patients treated with
      these recently available biologics need a careful monitoring.

PMID- 22385685
TI  - [Hereditary colorectal cancer].

PMID- 22385686
TI  - Negative life events, emotions and psychological difficulties as determinants of
      salivary cortisol in Belgian primary school children.
AB  - PURPOSE: This paper describes whether children's life events, emotions and
      psychological difficulties are related to their salivary cortisol patterns and
      whether this is different between sexes. METHODS: In 385 children (5-10 years
      old) participating in the ChiBS study, salivary cortisol samples were collected
      when waking up, 30 min and 60 min after wake up and in the evening on two
      consecutive weekdays. Moreover, data on children's life events, emotions and
      difficulties were collected. Statistical analysis was done separately for boys
      and girls by multilevel growth curve modelling with adjustments for age, body
      mass index, socio-economic status and wake up time. RESULTS: In boys and girls
      with more negative life events during the last three months, the diurnal cortisol
      slope was steeper (more decline). Boys with higher self-reported happiness showed
      lower overall, morning and evening cortisol levels. In contrast, the diurnal
      slope was steeper (more decline) in boys with emotional problems due to higher
      morning values. In girls, peer problems were associated with lower overall and
      morning cortisol levels. CONCLUSIONS: Children's salivary cortisol patterns were
      related to some negative life events, emotions and difficulties, although
      differently in boys and girls. As such, sex-differences in HPA functioning are
      already present in young children. Most findings support the upregulation of the
      cortisol response to stress, although lower morning values were found in the
      presence of peer problems in girls. Future studies should focus on sex
      differences, positive emotions and the diurnal cortisol slope.

PMID- 22385687
TI  - Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute
      lymphoblastic leukemia and healthy controls.
AB  - Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most
      common type. Since survival significantly improves over time, treatment-related
      side effects become increasingly important. Glucocorticoids play an important
      role in the treatment of ALL, but they may suppress the hypothalamic-pituitary
      adrenal (HPA) axis. The duration of HPA axis suppression is not yet well defined.
      The present study aimed at assessing the function of the HPA axis by determining
      the cortisol awakening response (CAR) and the dexamethasone (DEX) suppression
      test in children that were treated for childhood ALL, compared to a healthy age
      and sex matched reference group. In addition, questionnaires regarding sleep,
      fatigue, depression and quality of life were completed by the children and their
      parents. Fourty-three survivors who finished their treatment for childhood ALL 37
      (interquartile range 22-75) months before and 57 healthy controls were included.
      No differences in CAR were observed between ALL survivors and the reference
      group, but survivors of ALL had higher morning cortisol levels and an increased
      cortisol suppression in response to oral dexamethasone. Higher cortisol levels in
      childhood ALL survivors were associated with more fatigue and poorer quality of
      life. We conclude that the experience of a stressful life event in the past may
      have caused a long-term dysregulation of the HPA axis in childhood ALL survivors,
      as reflected in an increased cortisol production and an enhanced negative
      feedback mechanism.

PMID- 22385688
TI  - The rewarming benefit of anterior torso heat pad application in mildly
      hypothermic conscious adult trauma patients remains inconclusive.
AB  - The rewarming benefit of anterior torso heat pad application in mildly
      hypothermic conscious adult trauma patients remains inconclusive in this
      randomized comparative clinical trial. There was no between-group rewarming gain
      in ear canal temperature when an anterior torso chemical heat pad was compared
      with blankets. Patient awareness, and favorable perception of, being administered
      the active intervention (heat pad) could explain the significant improvement in
      patient-rated cold discomfort discerned with the heat pad. In the context of
      marginal demonstrated benefit, it would have been informative to ascertain
      adverse effects related to the heat pad, including burn injury to the chest wall.

PMID- 22385689
TI  - Flapless CAD/CAM-guided surgery for staged transition from failing dentition to
      complete arch implant rehabilitation: a 3-year clinical report.
AB  - The transition of patients from failing dentition to complete arch implant
      rehabilitation often requires that the patient be rendered edentulous and has to
      wear a complete removable dental prosthesis for varying periods of time. This is
      objectionable to many patients. A staged treatment approach allows a fixed
      interim restoration, patient comfort, and prosthodontic control throughout the
      rehabilitation process. CAD/CAM-guided flapless implant surgery has the advantage
      of prosthetically driven implant placement and minimal postoperative sequelae. A
      patient with a failing dentition was treated with this combined protocol and was
      followed up for 3 years after loading. Implant and prosthesis survival rates were
      100%, with no technical complications encountered up to the last recall. The
      purpose of this clinical report is to describe a combination of CAD/CAM-guided
      flapless surgery and a staged treatment approach, thereby giving the patient a
      tooth-supported or implant-supported fixed interim prosthesis during the entire
      rehabilitation process. The various surgical, laboratory, and prosthetic stages
      are illustrated for the complete arch prosthetic rehabilitation, and the 3-year
      follow-up outcome is reported.

PMID- 22385690
TI  - Radiographic detection and characteristic patterns of residual excess cement
      associated with cement-retained implant restorations: a clinical report.
AB  - Residual excess cement (REC) is a common complication of cement-retained
      prostheses and has been linked to periimplant disease. Removal of the cement
      residue may result in resolution of the issue if addressed early in the disease
      process. However, this is dependent upon the ability to locate and adequately
      remove the foreign material. This series of patient scenarios describes the
      ability to detect REC by using dental radiography. Characteristics related to
      cements and flow patterns specific to implants are addressed.

PMID- 22385691
TI  - Complex mandibular rehabilitation of a self-inflicted gunshot wound: a clinical
      report.
AB  - This report describes the surgical and prosthodontic rehabilitation of a patient
      traumatized by a self-inflicted gunshot wound to the mandible which required
      rehabilitation with a free fibula microvascular graft, single stage dental
      implant placement, and rehabilitation with CAD/CAM and laser assembled prosthetic
      components.

PMID- 22385692
TI  - The use of slow heating and slow cooling regimens to strengthen porcelain fused
      to zirconia.
AB  - STATEMENT OF PROBLEM: Porcelain fused to zirconia prostheses are widely used.
      However, porcelain chipping, spalling, fracture, and delamination are common
      clinical problems. Residual stresses of thermal origin have received attention,
      but clear data and firing guidelines remain absent. PURPOSE: The purpose of this
      study was to measure the influence of heating and cooling protocols on the
      strength of porcelain fused to zirconia. MATERIAL AND METHODS: A modified 4-point
      flexural testing technique was used to measure strength, and porcelain buttons
      were bonded to the beam between the 2 central loading points. Beams (n=54) were
      made of a tetragonal polycrystalline zirconium dioxide that was partially
      stabilized with an yttria core and a feldspathic dental porcelain. Three
      different heating rates and 3 different cooling regimens were used during firing.
      Two-way analysis of variance (ANOVA) was used to evaluate the 2 main effects of
      the heating and cooling regimens and their interaction with the delamination
      force (alpha=.05). The Tukey multiple comparisons test was used to identify
      differences among heating or cooling regimens. RESULTS: During loading, the
      porcelain buttons separated from the zirconia beams because of delamination
      within the porcelain, which was close to the porcelain to zirconia interface.
      ANOVA revealed that the effects of the cooling regimen and heating rate had
      statistically significant effects on failure load (P<.05). The effect of the
      cooling regimen was greater than that of the heating regimen. CONCLUSIONS: Slow
      cooling and slow heating regimens should be used when firing porcelain to
      zirconia. Cooling regimens were found to be more influential than heating rates.
      Failure was localized to the porcelain adjacent to the porcelain-zirconia
      interface, not to the interface itself, indicating that the residual stresses of
      thermal origin within the porcelain dominated. The preparation of zirconia with
      50 MUm aluminum oxide at a pressure of 0.34 MPa was sufficient to prevent
      interfacial failure.

PMID- 22385693
TI  - Survival and complications of zirconia-based fixed dental prostheses: a
      systematic review.
AB  - STATEMENT OF PROBLEM: Evidence is limited on the efficacy of zirconia-based fixed
      dental prostheses. PURPOSE: The purpose of this systemic review was to assess
      zirconia-based FDPs in terms of survival and complications. MATERIAL AND METHODS:
      Searches performed in PubMed databases were enriched by hand searches to identify
      suitable publications. The keywords used were: "zirconia" and "fixed dental
      prosthesis," "zirconia" and "crown," "zirconia" and "fixed partial denture" and
      "humans," "zirconia" and "crown" and "humans," "crown" and "all-ceramics," and
      "fixed partial denture" and "all-ceramics". Titles and abstracts were read to
      identify literature that fulfilled the inclusion criteria. Only peer reviewed
      clinical studies published in the English language from January 1999 through June
      2011 were included. RESULTS: Twelve clinical studies based on zirconia, framework
      design, and porcelain veneering technique met the inclusion criteria. Of the
      studies identified, 1 was a randomized clinical study with 3-year follow-up
      results; the others were cohort prospective studies. Clinical complications
      included chipping of veneering porcelain, abutment failure, and framework
      fracture. One study investigated pressed ceramics as the veneering material and
      found no chipping of veneering porcelain after 3 years. CONCLUSIONS: Short term
      clinical data suggest that zirconia-based fixed dental prostheses may serve as an
      alternative to metal ceramic fixed dental prostheses in the anterior and
      posterior dentition.

PMID- 22385694
TI  - Matching repeatability and interdevice agreement of 2 intraoral
      spectrophotometers.
AB  - STATEMENT OF PROBLEM: The visual determination of tooth color with standard shade
      guides is a subjective method of color communication, depending on variables such
      as the light source, the operator, and the tooth. The assessment of tooth color
      may be improved by the use of special devices such as colorimeters or
      spectrophotometers. However, the repeatability and the interdevice agreement of
      these devices have not been thoroughly investigated. PURPOSE: The purpose of this
      study was to evaluate the effect of different illuminants (natural daylight,
      dental unit lamp, and daylight lamp) on the matching repeatability of 2 intraoral
      spectrophotometers (Easyshade and SpectroShade). MATERIAL AND METHODS: The
      maxillary right central incisor and canine and the mandibular left central
      incisor of each of 10 dental students were measured by a single operator using
      both devices. The color of each tooth was assessed 3 times with each device under
      each of the 3 different illuminants (natural daylight, a dental unit lamp, and a
      daylight lamp). The device readings were expressed in Vitapan 3D-Master shade
      codes. Statistical analysis was performed and the level of agreement was assessed
      with the Spearman Correlation Coefficient. RESULTS: A particularly high to
      moderate level of agreement among the readings made under natural daylight, a
      dental unit lamp, and a daylight lamp was observed for both devices (P<.01),
      suggesting that their matching repeatability was not completely satisfactory for
      clinical practice. A moderate and a moderate to high level of agreement was found
      among Easyshade readings when the 3 different illuminants were used. The level of
      agreement for the respective SpectroShade readings was particularly high to high
      (P<.001). A particularly low level of agreement was found among the respective
      Easyshade and SpectroShade readings performed under any of the illuminants tested
      (P<.05), suggesting poor interdevice reliability. CONCLUSIONS: The matching
      repeatability of both devices under natural daylight, a dental unit lamp, and a
      daylight lamp was not completely satisfactory for clinical practice. The effects
      of different illuminants seem to be more pronounced for Spectroshade than for
      Easyshade. The interdevice agreement between the 2 devices tested was poor,
      suggesting that the 2 devices were not compatible.

PMID- 22385695
TI  - Supplementing retention through crown/preparation modification: an in vitro
      study.
AB  - STATEMENT OF PROBLEM: The best treatment for a crown that has come loose but has
      appropriate marginal fit and form is not clear. PURPOSE: This study was designed
      to determine whether the retention of such crowns can be increased without
      remaking the crown or by extensively modifying the tooth preparation. MATERIAL
      AND METHODS: Ninety cast metal complete crowns, divided into 9 groups of 10, were
      fabricated to be slightly loose in their internal adaptation to metal dies with
      an optimal tooth preparation. Horizontal grooves were formed around the
      circumference of the internal crown surface and the external surface of the metal
      die, the control being the unaltered crown and die. The crowns were cemented with
      resin-modified glass ionomer cement and then subjected to a tensile force until
      they were dislodged. The data were subjected to a 2-way ANOVA to determine the
      significance of the differences between crowns and dies, and 2 t tests were then
      used to compare each crown/die combination to the control (alpha=.05). RESULTS:
      The mean retention was significantly higher when 1 horizontal groove was placed
      inside the crowns (P<.001) and was even higher when 2 grooves were placed inside
      the crowns (P<.001). Placing 1 or 2 grooves in the metal die or in both the crown
      and die was not significantly more retentive than placing grooves only in the
      crown. CONCLUSIONS: Placing 1 or 2 horizontal circumferential grooves into the
      internal surface increased the retention of metal complete crowns made for
      optimal tooth preparations. Grooves placed into the crown were as effective as or
      more effective than grooves placed into the tooth / die.

PMID- 22385697
TI  - Radio frequency identification (RFID) of dentures in long-term care facilities.
AB  - STATEMENT OF PROBLEM: The difficulty of identifying the ownership of lost
      dentures when found is a common and expensive problem in long term care
      facilities (LTCFs) and hospitals. PURPOSE: The purpose of this study was to
      evaluate the reliability of using radiofrequency identification (RFID) in the
      identification of dentures for LTCF residents after 3 and 6 months. MATERIAL AND
      METHODS: Thirty-eight residents of 2 LTCFs in Switzerland agreed to participate
      after providing informed consent. The tag was programmed with the family and
      first names of the participants and then inserted in the dentures. After
      placement of the tag, the information was read. A second and third assessment to
      review the functioning of the tag occurred at 3 and 6 months, and defective tags
      (if present) were reported and replaced. The data were analyzed with descriptive
      statistics. RESULTS: At the 3-month assessment of 34 residents (63 tags) 1 tag
      was unreadable and 62 tags (98.2%) were operational. At 6 months, the tags of 27
      of the enrolled residents (50 tags) were available for review. No examined tag
      was defective at this time period. CONCLUSIONS: Within the limits of this study
      (number of patients, 6-month time span) RFID appears to be a reliable method of
      tracking and identifying dentures, with only 1 of 65 devices being unreadable at
      3 months and 100% of 50 initially placed tags being readable at the end of the
      trial.

PMID- 22385696
TI  - Wear of matrix overdenture attachments after one to eight years of clinical use.
AB  - STATEMENT OF PROBLEM: Matrices of unsplinted attachment systems are generally
      reported to be the weak component of implant overdentures, often requiring
      frequent maintenance. Clinical wear results in reduced retention of the
      prosthesis, requiring activation or renewal of the matrix to restore the initial
      level of retention. PURPOSE: The purpose of this retrospective study was to
      measure the wear of the matrix of a ball attachment after various periods of
      clinical wear. MATERIAL AND METHODS: Seventy specimens of 3 groups of matrices of
      ball attachments that had been in use for mean periods of 12.3 months (1Y group,
      n=26), 39.0 months (3Y group, n=28) and 95.6 months (8Y group, n=16) were
      retrieved from 35 patients (2 specimens per patient) and measured on a coordinate
      measuring machine equipped with a touch trigger probe. Ten unused matrices were
      used as controls (CTRL group). The external and internal matrix diameters and
      deviations from circularity were measured. For the various time periods, the
      decreases in matrix thickness were calculated and compared with controls. Kruskal
      Wallis 1-way ANOVA by ranks, followed by the Mann-Whitney post hoc tests, were
      conducted to test for differences in median values among groups (alpha =.05).
      RESULTS: For the internal upper diameter of the matrices tested, the Kruskal
      Wallis and Mann-Whitney tests revealed significant differences for the 3 groups
      compared to the controls. For group 1Y, a significant difference (P<.001) of the
      internal upper diameter was found compared to the CTRL group. Compared to the
      controls, the nonparametric analyses for groups 3Y and 8Y showed significant
      differences for the internal upper diameter (P<.001) and deviations from
      circularity (P<.001). For groups 1Y, 3Y and 8Y, matrix thickness losses were 07,
      47 and 70 MUm, respectively. CONCLUSIONS: Within the limitations of this study,
      it was observed that one year of clinical wear had limited effect on the ball
      attachment matrices. Three to 8 years of clinical use resulted in a significant
      decrease of matrix thickness, especially at the tip of the retentive lamellae.

PMID- 22385699
TI  - Denture marker using a two-dimensional bar code.

PMID- 22385701
TI  - When it comes to drug discovery not all Gram-negative bacterial biodefence
      pathogens are created equal: Burkholderia pseudomallei is different.

PMID- 22385702
TI  - Motivational Interviewing: moving from why to how with autonomy support.
AB  - Motivational Interviewing (MI), a counseling style initially used to treat
      addictions, increasingly has been used in health care and public health settings.
      This manuscript provides an overview of MI, including its theoretical origins and
      core clinical strategies. We also address similarities and differences with Self
      Determination Theory. MI has been defined as person-centered method of guiding to
      elicit and strengthen personal motivation for change. Core clinical strategies
      include, e.g., reflective listening and eliciting change talk. MI encourages
      individuals to work through their ambivalence about behavior change and to
      explore discrepancy between their current behavior and broader life goals and
      values. A key challenge for MI practitioners is deciding when and how to
      transition from building motivation to the goal setting and planning phases of
      counseling. To address this, we present a new three-phase model that provides a
      framework for moving from WHY to HOW; from building motivation to more action
      oriented counseling, within a patient centered framework.

PMID- 22385704
TI  - A plea for clarity.

PMID- 22385703
TI  - Using respiratory motion to guide planning target volume margins for external
      beam partial breast irradiation.

PMID- 22385705
TI  - Our pledge to achieve safety.

PMID- 22385706
TI  - We forget at our peril the lessons built into the alpha/beta model.

PMID- 22385708
TI  - On the parameters of the linear-quadratic model: in regard to the editorial by
      Glatstein.

PMID- 22385710
TI  - In regard to "Dose escalation in the radiation therapy of prostate cancer" (Int J
      Radiat Oncol Biol Phys 2011;80:1289-1291).

PMID- 22385711
TI  - Pelvic nodal radiotherapy in patients with unfavorable intermediate and high-risk
      prostate cancer: evidence, rationale, and future directions: in regard to
      Morikawa and Roach III (Int J Radiat Oncol Biol Phys 2011 May 1;80:6-16).

PMID- 22385713
TI  - Hypoxia, androgen deprivation and systemic metastases in prostate cancer (in
      response to "Antivascular effects of neoadjuvant androgen deprivation for
      prostate cancer: an in vivo human study using susceptibility and relaxitivity
      dynamic MRI": in regard to Alonzi R et al. (Int J Radiat Oncol Biol Phys
      2011;80(3):721-727).

PMID- 22385714
TI  - Treatment trends and outcomes of small-cell carcinoma of the bladder: in regard
      to Koay et al. (Int J Radiat Oncol Biol Phys 2011 Oct 20).

PMID- 22385715
TI  - Randomized clinical trial of weekly vs. triweekly cisplatin-based chemotherapy
      concurrent with radiotherapy in the treatment of locally advanced cervical
      cancer: in regard to Sang-Young Ryu et al. (Int J Radiat Oncol Biol Phys
      2011;81:e577-e581).

PMID- 22385716
TI  - Randomized clinical trial of weekly versus triweekly cisplatin-based chemotherapy
      concurrent with radiotherapy in treatment of locally advanced cervical cancer: in
      regard to Ryu et al. (Int J Radiat Oncol Biol Phys 2011;81:e577-e581).

PMID- 22385718
TI  - Increased risk of ischemic stroke in young nasopharyngeal carcinoma patients. in
      regard to Lee et al. (Int J Radiat Oncol Biol Phys 2011;81:e833-e838).

PMID- 22385719
TI  - Does sacrificing the deep lobe of parotid gland prevent marginal miss? In regard
      to Chen et al. (Int J Radiat Oncol Biol Phys 2011;80:1423-1429).

PMID- 22385721
TI  - In regard to "ACR appropriateness criteria of recurrent head-and-neck cancer
      after prior definitive radiation." (Int J Radiat Oncol Biol Phys 2011;80:1292
      1298).

PMID- 22385722
TI  - Fractionated stereotactic radiosurgery for reirradiation of head-and-neck cancer:
      in regard to Unger et al. (Int J Radiat Oncol Biol Phys 2010;77:1411-1419).

PMID- 22385724
TI  - Stereotactic radiosurgery for vestibular schwannomas: in regard to Kapoor et al.
      (Int J Radiat Oncol Biol Phys 2011;81:647-653).

PMID- 22385726
TI  - In Reply to Dr. Cashmore and colleagues: Lowering whole-body radiation doses in
      pediatric intensity - modulated radiotherapy through the use of unflattened
      photon beams: Cashmore J et al. (Int J Radiat Oncol Biol Phys 2011;80:1220-1227).

PMID- 22385727
TI  - In reply to Furweger et al. (Int J Radiat Oncol Biol Phys DOI:
      10.1016/j.ijrobp.2009.11.030).

PMID- 22385728
TI  - Health status of red mullets from polluted areas of the Spanish Mediterranean
      coast, with special reference to Portman (SE Spain).
AB  - A suite of general physiological indicators and hepatic biomarker responses were
      determined in red mullet (Mullus barbatus) from priority pollution areas of W
      Mediterranean Sea, including the highly metal polluted area of Portman
      (Cartagena, SE Spain). Concentrations of metals and persistent organic pollutants
      in fish muscle tissue and sediment samples were also analysed. Our results showed
      that fish from Portman accumulated the highest concentrations of mercury, lead
      and arsenic and also of some polycyclic aromatic hydrocarbons and polychlorinated
      biphenyls congeners. In addition, they had significantly lower condition factor,
      muscle lipid content and gonadosomatic index, as well as the lowest levels of DNA
      integrity and the highest ethoxyresorufin-O-deethylase (EROD) activity in liver
      of the areas investigated. Contaminant body burden in fish only partly
      corresponded to chemical characteristics of the sediments in the areas in which
      they were collected. Our findings indicate that red mullets from Portman had
      suboptimal health status that warrant further study.

PMID- 22385729
TI  - The obesity paradox--a scientific artifact?

PMID- 22385730
TI  - Anorexia nervosa patients display a deficit in membrane long chain poly
      unsaturated fatty acids.
AB  - BACKGROUND & AIMS: The energy deficit in anorexia nervosa (AN) results from a low
      energy and fat intake. Data from the literature are at odds about a deficiency in
      essential fatty acids (EFA), linoleic (LA) and alpha-linolenic (ALA) acid. The
      aim of the present study was to determine RBC phospholipid FA composition in AN
      patients, and to relate this FA profile to fat mass and BMI. We postulated that
      there should not be a deficit in EFA, because AN patients are in negative energy
      balance, and a significant supply of EFA arises from the lipolysis of AT
      triglycerides. METHODS: Twenty-two AN women (14.2 +/- 2.0 kg/m2 BMI) had a DEXA
      body composition analysis, and an analysis of FA composition in the phospholipids
      of red blood cell membranes by capillary gas chromatography. The control group
      was made of 25 healthy women. RESULTS: There was no EFA deficiency in RBC, i.e.
      no decrease in LA and ALA, and no rise in C20:3 n-9. However, long chain poly
      unsaturated FA (LC-PUFA), mainly those of the n-3 family were significantly
      reduced. A negative correlation was found between fat mass and ALA, with a
      critical fat mass close to 5 kg, under which ALA was dramatically increased.
      CONCLUSION: AN patients display a complex membrane FA profile without traits of
      EFA deficiency but with a deficiency in LC-PUFA. We propose that adipose tissue
      is an endogenous source of FA able to compensate for the reduced food intake in
      EFA, but unable to provide enough LC-PUFA.

PMID- 22385731
TI  - The ratio of energy expenditure to nitrogen loss in diverse patient groups--a
      systematic review.
AB  - BACKGROUND & AIMS: The ratio of energy expenditure to nitrogen loss respectively
      of energy to nitrogen provision (E/N) is considered a valuable tool in the
      creation of an enteral or parenteral formulation. Specific E/N ratios for
      parenteral nutrition (PN) have not yet been clearly defined. To determine the
      range of energy expenditure, nitrogen (protein) losses, and E/N ratios for
      various patient groups, we performed a systematic review of the literature.
      METHODS: Medline 1950-2011 was searched for all studies on patients or healthy
      controls reporting energy expenditure and nitrogen loss at the same time.
      RESULTS: We identified 53 studies with 91 cohorts which comprised 1107 subjects.
      Mean TEE +/- standard deviation (SD) was 31.2 +/- 7.2 kcal/kg BW/day in patients
      (n = 881) and 35.6 +/- 4.3 kcal/kg BW/day in healthy controls (n = 266). Mean
      total protein loss (TPL) was 1.50 +/- 0.57 g/kg BW/day in patients and 0.94 +/-
      0.24 g/kg BW/day in healthy controls. A non-linear significant correlation was
      found between TPL and the E/N ratio. CONCLUSION: The E/N ratio is not a constant
      value but decreases continuously with increasing protein loss. These variations
      should be considered in the nutritional support of patients.

PMID- 22385732
TI  - Validation of smoking-related virtual environments for cue exposure therapy.
AB  - Craving is considered one of the main factors responsible for relapse after
      smoking cessation. Cue exposure therapy (CET) consists of controlled and repeated
      exposure to drug-related stimuli in order to extinguish associated responses. The
      main objective of this study was to assess the validity of 7 virtual reality
      environments for producing craving in smokers that can be used within the CET
      paradigm. Forty-six smokers and 44 never-smokers were exposed to 7 complex
      virtual environments with smoking-related cues that reproduce typical situations
      in which people smoke, and to a neutral virtual environment without smoking cues.
      Self-reported subjective craving and psychophysiological measures were recorded
      during the exposure. All virtual environments with smoking-related cues were able
      to generate subjective craving in smokers, while no increase was observed for the
      neutral environment. The most sensitive psychophysiological variable to craving
      increases was heart rate. The findings provide evidence of the utility of virtual
      reality for simulating real situations capable of eliciting craving. We also
      discuss how CET for smoking cessation can be improved through these virtual
      tools.

PMID- 22385733
TI  - Incidence and risk factors for non-fatal overdose among a cohort of recently
      incarcerated illicit drug users.
AB  - BACKGROUND: Release from prison is associated with a markedly increased risk of
      both fatal and non-fatal drug overdose, yet the risk factors for overdose in
      recently released prisoners are poorly understood. The aim of this study was to
      identify risk and protective factors for non-fatal overdose (NFOD) among a cohort
      of illicit drug users in Vancouver, Canada, according to recent incarceration.
      METHODS: Prospective cohort of 2515 community-recruited illicit drug users in
      Vancouver, Canada, followed from 1996 to 2010. We examined factors associated
      with NFOD in the past six months separately among those who did and did not also
      report incarceration in the last six months. RESULTS: One third of participants
      (n=829, 33.0%) reported at least one recent NFOD. Among those recently
      incarcerated, risk factors independently and positively associated with NFOD
      included daily use of heroin, benzodiazepines, cocaine or methamphetamine, binge
      drug use, public injecting and previous NFOD. Older age, methadone maintenance
      treatment and HIV seropositivity were protective against NFOD. A similar set of
      risk factors was identified among those who had not been incarcerated recently.
      CONCLUSIONS: Among this cohort, and irrespective of recent incarceration, NFOD
      was associated with a range of modifiable risk factors including more frequent
      and riskier patterns of drug use. Not all ex-prisoners are at equal risk of
      overdose and there remains an urgent need to develop and implement evidence-based
      preventive interventions, targeting those with modifiable risk factors in this
      high risk group.

PMID- 22385735
TI  - The use and risk of portable electronic devices while cycling among different age
      groups.
AB  - INTRODUCTION: In the Netherlands, a survey was set up to monitor the extent of
      the use of portable, electronic devices while cycling amongst different age
      groups of cyclists and to estimate the possible consequences for safety. METHOD:
      The main research questions concerned age differences in the self-reported use of
      electronic devices while cycling, self-reported crash involvement and risk, and
      self-reported compensatory behaviour. Teen cyclists (12-17 years) and young adult
      cyclists (18-34 years) were more frequent users, and also more indiscriminate
      users of portable devices while cycling than middle-aged and older adult cyclists
      (35-49 years; 50+ years). RESULTS: After statistical correction for influences on
      crash risk of urbanization level, weekly time spent cycling, and cycling in more
      demanding traffic situations, the odds of being involved in a bicycle crash were
      estimated to be higher for teen cyclists and young adult cyclists who used
      electronic devices on every trip compared to same age groups cyclists who never
      used these devices. For middle-aged and older adult cyclists, the use of portable
      electronic devices was not a significant predictor of bicycle crashes, but
      frequency of cycling in demanding traffic situations was. Possible implications
      for education or legal measures are discussed. IMPACT ON INDUSTRY: Results may
      inform researchers, policy makers, and cyclists themselves. Educational campaigns
      may use risk information to warn young cyclists about risk of device use while
      cycling.

PMID- 22385734
TI  - Differential roles of thought suppression and dispositional mindfulness in
      posttraumatic stress symptoms and craving.
AB  - Exposure to traumatic events often results in severe distress which may elicit
      self-medication behaviors. Yet, some individuals exposed to trauma do not develop
      post-traumatic stress symptoms and comorbid addictive impulses. In the wake of
      traumatic events, psychological processes like thought suppression and
      mindfulness may modulate post-traumatic stress and craving for substances. We
      examined the differential roles of mindfulness and suppression in comorbid post
      traumatic stress and craving among a sample of 125 persons with extensive trauma
      histories and psychiatric symptoms in residential treatment for substance
      dependence. Results indicated that thought suppression, rather than extent of
      trauma history, significantly predicted post-traumatic stress symptom severity
      while dispositional mindfulness significantly predicted both post-traumatic
      stress symptoms and craving. In multiple regression models, mindfulness and
      thought suppression combined explained nearly half of the variance in post
      traumatic stress symptoms and one-quarter of the variance in substance craving.
      Moreover, multivariate path analysis indicated that prior traumatic experience
      was associated with greater thought suppression, which in turn was correlated
      with increased post-traumatic stress symptoms and drug craving, whereas
      dispositional mindfulness was associated with decreased suppression, post
      traumatic stress, and craving. The maladaptive strategy of thought suppression
      appears to be linked with adverse psychological consequences of traumatic life
      events. In contrast, dispositional mindfulness appears to be a protective factor
      that buffers individuals from experiencing more severe post-traumatic stress
      symptoms and craving.

PMID- 22385736
TI  - Measuring safety climate in elderly homes.
AB  - INTRODUCTION: Provision of a valid and reliable safety climate dimension brings
      enormous benefits to the elderly home sector. The aim of the present study was to
      make use of the safety climate instrument developed by OSHC to measure the safety
      perceptions of employees in elderly homes such that the factor structure of the
      safety climate dimensions of elderly homes could be explored. METHOD: In 2010,
      surveys by mustering on site method were administered in 27 elderly homes that
      had participated in the "Hong Kong Safe and Healthy Residential Care Home
      Accreditation Scheme" organized by the Occupational Safety and Health Council.
      RESULTS: Six hundred and fifty-one surveys were returned with a response rate of
      54.3%. To examine the factor structure of safety climate dimensions in our study,
      an exploratory factor analysis (EFA) using principal components analysis method
      was conducted to identify the underlying factors. The results of the modified
      seven-factor's safety climate structure extracted from 35 items better reflected
      the safety climate dimensions of elderly homes. The Cronbach alpha range for this
      study (0.655 to 0.851) indicated good internal consistency among the seven-factor
      structure. Responses from managerial level, supervisory and professional level,
      and front-line staff were analyzed to come up with the suggestion on effective
      ways of improving the safety culture of elderly homes. The overall results showed
      that managers generally gave positive responses in the factors evaluated, such as
      "management commitment and concern to safety," "perception of work risks and some
      contributory influences," "safety communication and awareness," and "safe working
      attitude and participation." Supervisors / professionals, and frontline level
      staff on the other hand, have less positive responses. The result of the lowest
      score in the factors - "perception of safety rules and procedures" underlined the
      importance of the relevance and practicability of safety rules and procedures.
      CONCLUSION: The modified OSHC safety climate tool provided better evidence of
      structural validity and reliability for use by elderly homes' decision makers as
      an indicator of employee perception of safety in their institution. IMPACT ON
      INDUSTRY: The findings and suggestions in the study provide useful information
      for the management, supervisors/professionals and frontline level staff to
      cultivate the safety culture in the elderly home sector. Most important, elderly
      homes can use the modified safety climate scale to identify problem areas in
      their safety culture and safety management practices and then target these for
      intervention.

PMID- 22385737
TI  - Adult-supervised practice driving for adolescent learners: The current state and
      directions for interventions.
AB  - INTRODUCTION: The aim of this study was to quantify and identify correlates to
      the amount of parent-supervised behind-the-wheel practice hours by novice teen
      drivers. METHODS: A national survey of 945 parents of recently licensed teen
      drivers was conducted. Multivariate logistic regression was used to identify
      factors related to the number of practice hours completed. RESULTS: Sixty-one
      percent of parents reported practicing 50 or more hours with their teen. Two
      parent involvement was associated with more practice hours, though use of a
      professional driving instructor was not. Parents of teens licensed in states
      mandating 50 or more hours of practice driving were more likely to report at
      least 50 practice hours than those in states mandating 20-40 hours or in states
      without mandates. IMPACT ON INDUSTRY: The findings underscore the integral role
      of parents in the learning to drive process and provide further support for GDL
      requirements for practice hours.

PMID- 22385738
TI  - National evaluation of the effect of graduated driver licensing laws on teenager
      fatality and injury crashes.
AB  - PROBLEM: Automobile crashes remain a prominent cause of death and injury for
      teenagers in the United States. While it is generally agreed that graduated
      drivers licensing (GDL) influences crash rates, it is unclear which components
      have the strongest effect on any specific types of crashes. METHOD: We analyze
      the relative effect of different stages of GDL on teenage fatal and injury crash
      risk via a negative binomial generalized linear model with random state effects.
      Overall, nighttime, and crashes with multiple teenage passengers are considered.
      RESULTS: The strongest effects are seen by 16-year-olds, for which a strict
      permit stage is associated with a 58% reduction in fatal crash risk over a
      lenient permit stage. Similar reductions are seen for injury crashes. The
      intermediate stage, involving nighttime and passenger restrictions, is associated
      with a 44% reduction in fatalities but has relatively little effect on injury
      crashes. The strongest effects are generally seen for passenger crashes, followed
      by nighttime, and then overall crashes. IMPACT ON INDUSTRY: This study identifies
      stronger relationships between GDL and crash risk than has previously been
      discovered and captures the relative effects of permit and intermediate licensing
      restrictions, two high-level components of GDL which differ in intent and
      implementation.

PMID- 22385739
TI  - Reducing impaired driving through the identification of Repeat Target Vehicles: A
      case study.
AB  - INTRODUCTION: One of the most persistent groups of impaired drivers that are
      seemingly unaffected by social pressure, moral appeals, and the fear of arrest is
      that of the repeat impaired driver. This smaller group accounts for a
      disproportionate number of all impaired driving trips, often with high blood
      alcohol contents. New approaches are needed to identify and deal with the repeat
      impaired driver. METHOD: We propose a method based on the discovery that almost
      10% of all impaired driving calls for service involve repeat vehicles. Using the
      number of times a vehicle appears in our data, the average time to repeat, and
      the personality characteristics of the repeat impaired driver, we are able to
      create a comprehensive and predictive description of a Repeat Target Vehicle
      (RTV). CONCLUSIONS: Our method provides an opportunity to explore new and
      innovative crime reduction strategies that were never before possible.

PMID- 22385740
TI  - On-board safety monitoring systems for driving: review, knowledge gaps, and
      framework.
AB  - INTRODUCTION: Fatal highway incidents remain the leading type of fatal work
      related event, carrying tremendous personal, social, and economic costs. While
      employers with a fixed worksite can observe and interact directly with workers in
      an effort to promote safety and reduce risk, employers with workers who operate a
      motor vehicle as part of their job have fewer options. New technologies such as
      on-board safety monitoring systems offer the potential to further improve safety.
      These technologies allow vehicle owners to collect safety-specific information
      related to a driver's on-the-road behavior and performance. While many such
      devices are being developed and implemented in both commercial fleets and private
      vehicles, the scientific examination of these devices has lagged by comparison.
      METHOD: In the current paper, we: (a) describe the general features and
      functionality of current generations of on-board monitoring devices and how they
      might impact various driver behaviors; (b) review the current state of scientific
      knowledge specific to on-board devices; (c) discuss knowledge gaps and potential
      areas for future research, borrowing from the related domain of computer-based
      electronic performance monitoring (EPM); and (d) propose a framework that can be
      used to explore some of the human-system interactions pertaining to monitoring
      systems. IMPACT ON INDUSTRY: Motor vehicle crashes can carry tremendous costs for
      employers, in terms of injury, disability, and loss of potentially productive
      work years. New technologies can offer tremendous benefits in terms of promoting
      safer on-the-road behaviors.

PMID- 22385741
TI  - The influence of rear turn-signal characteristics on crash risk.
AB  - INTRODUCTION: The relationship between the relative risk of a rear-end collision
      during a turn, merge, or lane change maneuver and the characteristics of the rear
      turn-signal configuration was examined using crash data from seven states in the
      United States. METHOD: Rear turn-signal characteristics-including color, optics,
      separation, and light source-were identified for 55 vehicle models and used in a
      logistic regression analysis to model the odds of a rear-end collision.
      Additional variables including driver demographics (gender, age), vehicle age,
      and light condition were also modeled. Risk was assessed using a contrast group
      of striking vehicles in similar collisions. RESULTS: The results suggest that the
      odds of being the struck vehicle were 3% to 28% lower among vehicles equipped
      with amber versus red turn signals. Although the analysis suggests that there may
      be a safety benefit associated with amber rear turn signals, it is unclear
      whether turn-signal color alone is responsible. IMPACT ON INDUSTRY: The results
      suggest that aspects of a vehicle's rear signal characteristics may influence
      crash risk.

PMID- 22385742
TI  - Occupational injury in America: An analysis of risk factors using data from the
      General Social Survey (GSS).
AB  - INTRODUCTION: Although much is known about the distribution of occupational
      injury in terms of various job and employment factors, considerably less is known
      about other possible risk factors, particularly those involving psychosocial and
      organizational factors. These factors have not been emphasized in most injury
      surveillance systems or large scale, population based surveys. METHOD: In this
      study, data from the 2002 General Social Survey (GSS) and NIOSH Quality of Work
      Life (QWL) module were used to examine the risk of occupational injury in terms
      of socio-demographic factors, employment characteristics, and organizational
      factors. RESULTS: The most informative results were obtained from Poisson
      regression analyses, which identified race, occupational category, and work
      family interference as risk factors, and safety climate and organizational
      effectiveness as protective factors for occupational injury. These results
      provide guidance for targeting interventions and protective measures to curtail
      occupational injury in the United States.

PMID- 22385743
TI  - Traffic environment and demographic factors affecting impaired driving and
      crashes.
AB  - INTRODUCTION: Data availability has forced researchers to examine separately the
      role of alcohol among drivers who crashed and drivers who did not crash. Such a
      separation fails to account fully for the transition from impaired driving to an
      alcohol-related crash. METHOD: In this study, we analyzed recent data to
      investigate how traffic-related environments, conditions, and drivers'
      demographics shape the likelihood of a driver being either involved in a crash
      (alcohol impaired or not) or not involved in a crash (alcohol impaired or not).
      Our data, from a recent case-control study, included a comprehensive sampling of
      the drivers in nonfatal crashes and a matched set of comparison drivers in two
      U.S. locations. Multinomial logistic regression was applied to investigate the
      likelihood that a driver would crash or would not crash, either with a blood
      alcohol concentration (BAC)=.00 or with a BAC>=.05. CONCLUSIONS: To our
      knowledge, this study is the first to examine how different driver
      characteristics and environmental factors simultaneously contribute to alcohol
      use by crash-involved and non-crash-involved drivers. This effort calls attention
      to the need for research on the simultaneous roles played by all the factors that
      may contribute to motor vehicle crashes.

PMID- 22385745
TI  - "The Driver Behaviour Questionnaire as a predictor of accidents: A meta-analysis"
      Comments.

PMID- 22385751
TI  - Promoting physical activity: development and testing of self-determination theory
      based interventions.
AB  - A growing number of studies have pulled from Deci and Ryan's Self-Determination
      Theory to design interventions targeting health behavior change. More recently,
      researchers have begun using SDT to promote the adoption and maintenance of an
      active lifestyle. In this review, we aim to highlight how researchers and
      practitioners can draw from the SDT framework to develop, implement, and evaluate
      intervention efforts centered on increasing physical activity levels in different
      contexts and different populations. In the present paper, the rationale for using
      SDT to foster physical activity engagement is briefly reviewed before particular
      attention is given to three recent randomized controlled trials, the Canadian
      Physical Activity Counseling (PAC) Trial, the Empower trial from the UK, and the
      Portuguese PESO (Promotion of Health and Exercise in Obesity) trial, each of
      which focused on promoting physical activity behavior. The SDT-based intervention
      components, procedures, and participants are highlighted, and the key findings
      that have emanated from these three trials are presented. Lastly, we outline some
      of the limitations of the work conducted to date in this area and we acknowledge
      the challenges that arise when attempting to design, deliver, and test SDT
      grounded interventions in the context of physical activity promotion.

PMID- 22385752
TI  - Bacterial communities are sensitive indicators of contaminant stress.
AB  - With many environments worldwide experiencing at least some degree of
      anthropogenic modification, there is great urgency to identify sensitive
      indicators of ecosystem stress. Estuarine organisms are particularly vulnerable
      to anthropogenic contaminants. This study presents bacterial communities as
      sensitive indicators of contaminant stress. Sediments were collected from
      multiple sites within inner and outer zones of three heavily modified and three
      relatively unmodified estuaries. Bacterial communities were censused using
      Automated Ribosomal Intergenic Spacer Analysis and analysed for a suite of metal
      and PAH contaminants. Shifts in both bacterial community composition and
      diversity showed strong associations with sediment contaminant concentrations,
      particularly with metals. Importantly, these changes are discernable from
      environmental variation inherent to highly complex estuarine environments.
      Moreover, variation in bacterial communities within sites was limited. This
      allowed for differences between sites, zones and estuaries to be explained by
      variables of interest such as contaminants that vary between, but not within
      individual sites.

PMID- 22385753
TI  - Trends in marine debris along the U.S. Pacific Coast and Hawai'i 1998-2007.
AB  - We assessed amounts, composition, and trends of marine debris for the U.S.
      Pacific Coast and Hawai'i using National Marine Debris Monitoring Program data.
      Hawai'i had the highest debris loads; the North Pacific Coast region had the
      lowest debris loads. The Southern California Bight region had the highest land
      based debris loads. Debris loads decreased over time for all source categories in
      all regions except for land-based and general-source loads in the North Pacific
      Coast region, which were unchanged. General-source debris comprised 30-40% of the
      items in all regions. Larger local populations were associated with higher land
      based debris loads across regions; the effect declined at higher population
      levels. Upwelling affected deposition of ocean-based and general-source debris
      loads but not land-based loads along the Pacific Coast. LNSO decreased debris
      loads for both land-based and ocean-based debris but not general-source debris in
      Hawai'i, a more complex climate-ocean effect than had previously been found.

PMID- 22385754
TI  - Impact of air gun noise on the behaviour of marine fish and squid.
AB  - In this study various species of captive marine fish and one species of squid
      were exposed to the noise from a single air gun. Six trials were conducted off
      the coast of Western Australia with each trial using a different noise exposure
      regime. Noise levels received by the animals ranged between 120 and 184 dB re 1
      MUPa(2).s (SEL). Behavioural observations of the fish and squid were made before,
      during and after air gun noise exposure. Results indicate that as air gun noise
      levels increase, fish respond by moving to the bottom of the water column and
      swimming faster in more tightly cohesive groups. Significant increases in alarm
      responses were observed in fish and squid to air gun noise exceeding 147-151 dB
      re 1 MUPa SEL. An increase in the occurrence of alarm responses was also observed
      as noise level increased.

PMID- 22385756
TI  - Usefulness of beta-blocker therapy and outcomes in patients with pulmonary
      arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a disorder in which pulmonary arterial
      remodeling and vasoconstriction progressively lead to right heart failure (HF),
      exercise intolerance, and high mortality. Beta-blockers have been shown to
      decrease mortality in left-sided HF, but their efficacy in isolated right HF
      associated with PAH is uncertain. Patients with PAH may have cardiac co
      morbidities for which beta-blocker therapy is indicated, and the relative risk
      benefit of this therapy remains to be proved. This is a prospective cohort study
      of 94 consecutive patients with PAH divided into 2 groups with and without beta
      blocker use at baseline. Rate of all-cause mortality, PAH-related
      hospitalization, change in 6-minute walk test, right ventricular structure and
      function measured by echocardiography, and hemodynamics measured by right heart
      catheterization were determined between subjects with and without beta-blocker
      use. Beta-blocker use was common (28%) in this cohort. After a median follow-up
      of 20 months, changes in pulmonary hemodynamics and right ventricular size and
      function were similar between groups. There were no statistically significant
      differences in adverse events including PAH-related hospitalization or all-cause
      mortality (p = 0.19), presence of right HF by last visit (p = 0.75), or change in
      last 6-minute walk distance (p = 0.92). In conclusion, beta-blocker use is not
      uncommon in a select group of patients with PAH and cardiac co-morbidities and
      did not appear to exert detrimental effects in clinical, functional, and
      hemodynamic outcomes. Further randomized data are needed to evaluate the
      potential benefits and risks of beta-blocker use in patients with PAH.

PMID- 22385757
TI  - [Health agenda of the Mexican Institute of Social Security (1944-2010)].

PMID- 22385758
TI  - [Effect of photocoagulation on center point thickness in diabetic macular edema].
AB  - BACKGROUND: Photocoagulation is the standard treatment for clinically significant
      macular edema (CSME). This procedure is effective in reducing macular thickening,
      but it has been reported that initially it does not improve the thickness at the
      area of best visual function (center point of the fovea). We undertook this study
      to compare the effect of focal photocoagulation on center point thickness (CPT)
      and macular volume 3 weeks after treatment in Mexican diabetic patients with
      CSME, with and without center point involvement. METHODS: We carried out an
      observational, retrospective, longitudinal, analytical, open study. Type 2
      diabetic patients undergoing focal photocoagulation for CSME at a general
      hospital in Mexico City were evaluated. Mean CPT and macular volume were compared
      before and 3 weeks after photocoagulation (paired t test) in the sample and in
      eyes with (group 1) and without (group 2) baseline center point involvement.
      Absolute and percent CPT and macular volume changes were identified. RESULTS:
      Fifty-nine eyes (mean age 59.6 years) were studied. CPT mean increased from 193
      to 197 MUm (p = 0.3), statistically in group 2 (168.8 to 178.5 MUm, p <0.001).
      Macular volume mean changed from 7.8 to 7.6 mm(3) (p <0.001). CPT increased 3.9
      MUm (3%) in the sample, whereas macular volume decreased 0.26 mm(3) (3.1%).
      Correlation between changes was 0.089. CONCLUSIONS: Although macular volume
      decreased statistically 3 weeks after photocoagulation, CPT did not and increased
      statistically in eyes without baseline center point involvement, which was
      unnoticed in the sample effect. These changes should not be overlooked because
      dealing with them could improve the early results of treatment.

PMID- 22385759
TI  - [Breast cancer screening: have there been any changes during the last decade? A
      study in a Spanish unit].
AB  - BACKGROUND: Breast screening programs in Spain cover almost 100% of population.
      The objective of the present study was to analyze if there have been any changes
      during the last decade in our breast screening unit (Unidad de Prevencion del
      Cancer de Mama de Castellon) that can also be extrapolated to other breast
      screening units. METHODS: We conducted a retrospective and descriptive analysis
      reviewing patients seen in our breast screening unit between January 1, 2000 and
      December 31, 2009. Patients with a final diagnosis of carcinoma, year of
      diagnosis, age, histological type, infiltration, surgical procedure and tumor
      extension were analyzed. RESULTS: A total of 311 breast cancers were diagnosed
      among 90,010 women who were seen at our breast screening unit. Mean age of the
      patients was 56 years. A progressive increase of the target population was seen
      (24,004 persons in 2000 and 31,950 in 2009). Histological type, percentage of
      infiltrative tumors and lymph node involvement did not show significant
      differences by year. Differences were observed for tumor size (pT category of TNM
      classification) and breast conservation surgery. CONCLUSIONS: Tumor stage in
      cancers diagnosed in breast screening units progressively decreased when the
      program was being implemented. There is a maximum level among which tumor
      characteristics remain constant. Changes in screening programs can modify these
      characteristics.

PMID- 22385760
TI  - [Experience in the management of the severe form of human influenza A H1N1
      pneumonia in an intensive care unit].
AB  - BACKGROUND: At the beginning of the second trimester of 2009 there was an
      influenza A (H1N1) outbreak. The aim of this study is to describe the clinical
      presentation and mortality of the severe form of pneumonia in patients with human
      influenza A H1N1. METHODS: We conducted a retrospective review of all files of
      confirmed and suspected patients with severe human influenza A (H1N1) pneumonia.
      RESULTS: We studied 26 patients admitted to the ICU from April 1 to December 31,
      2009, among which 16 were males (61.54%) and 10 females (38.46%) with an average
      age of 52.26 +/- 15.48 years. The time of onset of symptoms to admission to the
      ICU was 6.3 +/- 3.19 days. The most frequent symptoms and signs were salmonated
      sputum (47%), chills (45%), dry cough (44%) and myalgia (42%). The mortality rate
      was 19.23%. The treatment was based on antiviral therapy, modulating inflammation
      and ventilatory techniques to optimize oxygenation. There was an association
      between combined therapy based on methylprednisolone, activated protein C and
      statins with a better survival (p = 0.05). CONCLUSIONS: Pneumonia virus of human
      influenza A (H1N1) is associated with high morbidity and mortality. According to
      our results, it is recommended to make an early diagnosis and to initiate a
      treatment regimen based on treatment bundles designed to optimize oxygenation,
      reduce viral load and modulate inflammation.

PMID- 22385761
TI  - [Solitary fibrous tumor. Clinic and pathological study of 16 cases].
AB  - BACKGROUND: Solitary fibrous tumor (SFT) is a localized fibrous mesothelioma and
      was originally described as a benign pleural lesion. It is a mesenchymatous
      lesion that has been found in different structures and tissues of the human
      organism. It originates from a stromal fibroblastic cell positive to CD4. We
      undertook this study to determine the clinical and histopathological
      characteristics of SFT found from January 1, 2002--January 31, 2010 in a
      concentrated third-level general hospital in Mexico City. METHODS: We present 16
      resected cases of different localizations: three pleural, three mediastinal,
      three lung, two oral cavity, one nasopharyngeal, one in the lateral aspect of the
      neck, one kidney, one paratesticular and another in the crural region. All were
      studied with hematoxylin and immunoperoxidase. RESULTS: There was similar
      affection in both genders. Mean age was 51 years (range: 43-81 years). Two
      pleural cases presented recurrence and one had hypoglycemia but none demonstrated
      metastases. No deaths were registered during a mean follow-up of 18 months.
      Histological pattern corresponded to a fusocellular growth that coincided with
      hemangiopericytoid zones in five cases and sarcomatoid in four. These cases were
      considered as mixed. All were positive to vimentin. CONCLUSIONS: Definitive
      diagnosis must be made by immunoperoxidase. Immediate treatment is surgical
      resection; relapses.

PMID- 22385762
TI  - [Diabetes in Mexico. CARMELA study].
AB  - BACKGROUND: Diabetes has demonstrated an epidemic behavior in Mexico, which is
      among the top countries with the highest number of patients with diabetes. The
      objective of this study was to estimate the prevalence of type 2 diabetes in
      Mexico City and its relation with some cardiovascular risk factors. METHODS: A
      cross-sectional study was conducted. A total of 1,772 adults of both genders,
      aged 25 to 64 years, were randomly selected. Type 2 diabetes and impaired fasting
      glucose prevalence were estimated as well as its relation with some
      cardiovascular risk factors such as hypertension, dyslipidemia, obesity,
      abdominal obesity and the common carotid artery intima-media thickness. RESULTS:
      The prevalence of type 2 diabetes was 9.7% in women and 8.0% in men. An age
      effect was evident. The proportion of patients who were unaware of having
      diabetes was 26%. The main risk factors related to diabetes were age, abdominal
      obesity, hypertension, low high-density cholesterol lipoproteins (HDL-c) and
      hypertriglyceridemia. Metabolic control was low. CONCLUSIONS: Prevalence of type
      2 diabetes in Mexico is high and is a major health problem. Its close relation
      with cardiovascular risk factors demand health policies aimed to diminish risk
      factors related to its occurrence.

PMID- 22385763
TI  - [Homocysteine after a methionine load in healthy subjects with adequate B-vitamin
      status].
AB  - BACKGROUND: Plasma homocysteine (Hcy) determination at 6-8 h after an oral
      methionine load (OML) allows for identification of some, but not all, individuals
      at risk to develop cardiovascular disease. It is probable that in some cases the
      Hcy increases occur later, or it elevates between normal ranges but in a
      sustained manner. However, the entire Hcy response curve has not been described.
      We undertook this study to determine Hcy concentrations from baseline to 24- and
      48-h after an OML in non-B-vitamin deficient adult subjects with other risk
      factors for high levels of Hcy such as smoking and overweight. METHODS: In a
      cross-over, clinical design, Hcy concentrations were determined at 2-h intervals
      throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6
      (VB6) concentrations were measured by high-performance liquid chromatography
      (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay
      (RIA). Statistical analysis included delta values and areas under the curve.
      Student t-test and repeated measurement analyses were conducted to control for
      confounders. RESULTS: Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12
      status were included. The maximum Hcy concentration occurred 8 h after the load
      and returned to baseline concentrations after 24 h. All subjects presented Hcy
      after the load within normal ranges, but smoking and overweight synergistically
      influenced the response to the challenge, producing a sustained elevation after
      the dose. CONCLUSIONS: Hcy concentrations after an OML remained above baseline
      for at least 24 h. Smoking and overweight affected the response to the methionine
      challenge.

PMID- 22385764
TI  - [Psychosocial adjustment in colorectal cancer patients undergoing chemotherapy or
      chemoradiotherapy].
AB  - BACKGROUND: Psychosocial adaptation is a measurement that represents the
      patient's adjustment to those changes involved in their illness. We undertook
      this study to search for individual characteristics and clinical aspects
      associated with successful psychosocial adjustment in patients with colorectal
      cancer (CRC) undergoing (CT) chemotherapy or chemoradiotherapy (CRT). METHODS:
      Seventy-five patients with CRC treated with CT or CRT in a cancer center were
      included. Psychosocial Adjustment to Illness Scale Self-Reporting (PAIS-SR)
      questionnaire was used as a measurement of psychosocial adjustment. RESULTS:
      Psychosocial adaptation was successful in 18 patients (24%) and unsuccessful in
      57 patients (76%). Young patients, married patients and males showed lower
      psychosocial adaptation to disease. This is associated with the decrease in
      sexual relations, economic resources and psychological symptoms. Patients
      complained that they were unsatisfied due to the lack of disease and treatment
      information offered by the heath care team. CONCLUSIONS: In the process of
      adaptation, clinical features such as tumor location and treatment scheme are
      considered basic, as well as age, education, marital status. Areas such as
      sexuality, interpersonal and family relationships, economic status and emotional
      state of patients affected by the disease and treatments provide a deep
      complexity in the study of the psychosocial adaptation process in patients with
      CRC.

PMID- 22385765
TI  - [Comparative study of the cost/effectiveness of surgical wash with various
      antiseptics].
AB  - BACKGROUND: "Surgical scrub" of the hands and arms is a fundamental procedure for
      reducing infection risk. We undertook this study in order to compare different
      antiseptics and their microbicidal effects, costs and times of the procedures.
      METHODS: Thirty students followed the surgical scrub procedure using benzalkonium
      chloride. Seven days later the students used povidone-iodine and, 7 days after
      that, they used chlorhexidine/alcohol. After the surgical scrub, cultures were
      obtained from the palms of their hands and from their nail beds. The students
      wore sterile gloves, which were removed 30 min later to obtain new cultures from
      the same sites. The cost of the products was calculated in Mexican pesos and the
      time of each procedure was measured in minutes. RESULTS: There was a
      statistically significant difference in the number of colony-forming units
      (CFUs). The number of CFUs was lower in the groups of students who used
      chlorhexidine/alcohol and povidone-iodine as compared to the benzalkonium
      chloride group. There was no difference between chlorhexidine/alcohol and
      povidone-iodine. Costs were higher for povidone-iodine and benzalkonium chloride
      compared to chlorhexidine/alcohol. Procedure times were similar with povidone
      iodine and benzalkonium chloride but the time was reduced approximately five
      times when using chlorhexidine/alcohol. CONCLUSIONS: It is a proven fact that the
      lack of surgical scrub favors wound infections, longer hospital stays and
      increased costs. Therefore, further studies are needed to determine the best
      antiseptic according to cost/benefit. Chlorhexidine/alcohol proved to be the
      superior antiseptic in terms of cost/benefit compared to povidone-iodine and
      benzalkonium chloride.

PMID- 22385766
TI  - [Resistance to thyroid hormone and Hashimoto's thyroiditis].
AB  - BACKGROUND: Resistance to thyroid hormone (RTH) is a rare condition characterized
      by elevation of thyroid stimulating hormone (TSH) and thyroid hormones (TH). Its
      association with Hashimoto's thyroiditis was described in 1993 and occurs in 1 of
      1.3 million births. CLINICAL CASE: We present a female patient with a family
      history of hypothyroidism. The patient's condition began in 2008 with symptoms of
      hyperthyroidism, elevated triiodothyronine (T3), thyroxine (T4) and TSH levels.
      Thyroid scan showed hypermetabolic activity and she was positive for anti
      peroxidase antibodies (anti-TPO). After administration of thiamazole, TSH
      increased. In 2009 she was diagnosed with clinical hypothyroidism, high levels of
      TSH, and normal T3 and T4 levels. Levothyroxine was prescribed but TSH increased
      and she presented clinical signs of hyperthyroidism. Patient abandoned treatment
      after 1 month. Her symptoms fluctuated among hyperthyroidism, euthyroidism and
      hypothyroidism. In 2010 she presented tachycardia, weight loss, and high T3, T4
      and TSH levels. Thyrotropin-secreting adenoma (TSHoma) was suspected and ruled
      out by magnetic resonance imaging (MRI). Thyrotropin releasing hormone (TRH) test
      was performed. TSH increased and the alpha-subunit of pituitary hormones retained
      low levels. CONCLUSIONS: RTH diagnosis requires exclusion of a TSHoma because
      both present a similar pattern according to thyroid tests. The association
      between Hashimoto's thyroiditis and RTH is not well known. This pathological
      condition has a mutated TRbeta gene in 75% of the cases.

PMID- 22385767
TI  - [Peritoneal metastases of medulloblastoma due to placement of
      ventriculoperitoneal shunt in an adult patient].
AB  - BACKGROUND: Medulloblastoma is a highly aggressive tumor of the posterior fossa.
      It is more common in children and has a very low incidence in adults. This tumor
      may cause endocranial hypertension, which requires placement of a
      ventriculoperitoneal shunt after surgical resection. It is possible, however,
      that neoplastic cells found in the cerebral spinal fluid can migrate through the
      shunt and implant themselves into the peritoneal cavity, producing multiple
      metastases that create great difficulty in treatment and offer a poor prognosis.
      This event is extraordinarily rare, which explains the few published cases and
      the lack of guidelines for treatment. CLINICAL CASE: We present a 26-year-old
      male with a history of medulloblastoma of the cerebellum that was treated by
      complete tumor resection, radiotherapy and placement of a ventriculoperitoneal
      shunt. Two years later the patient demonstrated severe abdominal pain caused by
      the presence of multiple irresectable tumors in the abdomen and pelvis. A
      percutaneous biopsy documented metastatic medulloblastoma and the patient was
      treated with neoadjuvant chemotherapy based on schemes used for pediatric
      patients. There was a significant reduction in tumor activity that later allowed
      complete tumor resection. CONCLUSIONS: In adult patients, peritoneal metastases
      from medulloblastoma are an unusual event. With this surgical and clinical case,
      we can suggest new guidelines for diagnosis and treatment to obtain satisfactory
      results.

PMID- 22385768
TI  - [Bezoar after ingestion of metallic foreign bodies].
AB  - BACKGROUND: Ingestion of foreign bodies represents a common feature in
      psychiatric patients and prisoners. Bezoar is a conglomeration of partially or
      undigested foreign material in the gastrointestinal tract. These are classified
      into several types according to the materials which they are composed of, the
      least frequent being metals. There are few cases reported in the literature.
      CLINICAL CASE: We report a case of a patient with a pathological history of
      mental disorder. The patient complained of abdominal pain 24 h prior, and there
      were no other symptoms. Physical examination revealed pain in the upper quadrant
      without peritoneal irritation. Laboratory tests were normal and plain x-ray of
      the abdomen showed several metallic foreign bodies, some sharp, >5 cm in length
      and with intestinal prolongation. Surgical intervention was performed several
      hours later: gastrotomy to remove the gastric bezoar that was composed of several
      screws, nails, scrap metal, lighters, clothespins, radio antennas and one coin.
      Four metallic foreign bodies were found in the small bowel after reviewing the
      abdominal cavity, so enterotomy was also performed to remove them. Postoperative
      course was uneventful. CONCLUSIONS: Surgical treatment must be considered in
      cases of multiple, large, sharp objects or complications. An exhaustive study of
      the case is essential to avoid delay in treatment and potential complications.

PMID- 22385769
TI  - [Robot-assisted laparoscopic radical cystoprostatectomy and construction of
      totally intraabdominal orthotopic bladder with ileal segment. Initial experience
      in Mexico].
AB  - BACKGROUND: Bladder and surrounding tissue resection followed by creation of a
      continent urinary reservoir is the gold standard treatment for invasive bladder
      cancer. In recent years, the da Vinci robot has played a major role in this
      procedure. Our objective was to describe our surgical technique, a robot-assisted
      laparoscopic radical cystoprostatectomy and totally intrabdominal ortothopic
      ileal neobladder construction (Studer). CLINIC CASE: We present the case of a 79
      year-old male patient with a diagnosis of transitional cell bladder carcinoma.
      The patient underwent radical cystoprostatectomy with urinary diversion. The
      procedure was performed with the use of the da Vinci Surgical System (Intuitive
      Surgical, Sunnyvale, CA). Total operative time was 7 h, and the estimated blood
      loss was 500 ml. There were no intra- or postoperative complications, and the
      patient's hospitalization was 7 days. At early follow-up, oncological and
      functional results were favorable. CONCLUSIONS: Robot-assisted cystoprostatectomy
      and urinary diversion are feasible techniques, although their role in management
      of infiltrative bladder cancer is not well defined.

PMID- 22385770
TI  - [Massive transfusion and trauma patient management: pathophysiological approach
      to treatment].
AB  - Bleeding that requires massive blood transfusion is one of the main causes of
      cardiac arrest and death in the operating room. Its mortality varies widely
      between 15 and 54%, and it is strongly related to multiple factors such as
      acidosis, hypothermia and hypocoagulation. We undertook this study to describe
      the mechanisms that perpetuate bleeding during massive hemorrhage and the
      particular issues under the different clinical conditions of controlled and
      uncontrolled tissue damage. Laboratory tests for coagulation status diagnosis as
      well as treatment guidelines for usage of different fluid replacement solutions
      and hemoderivatives are described. A well-established response plan is needed by
      the surgical team and the blood bank in order to quickly facilitate blood
      products to the patient. Measures to avoid hypothermia and availability of rapid
      infusion systems are also necessary.

PMID- 22385771
TI  - [Rectal cancer: diagnosis, screening and treatment].
AB  - Rectal cancer is one of the primary malignant neoplasms  occurring in Mexican
      patients of reproductive age. Unfortunately, randomized studies in rectal cancer
      do not exist as they do with well-recognized colon cancer. We must individualize
      the epidemiology, risk factors, diagnostic approach, staging and treatment
      because management is different in rectal cancers affecting the mid- and lower
      third of the rectum than in the upper third and in colon cancers. Histological
      staging is the primary prognostic factor. TNM staging (tumor, node, and
      metastasis) is used internationally by the American Joint Committee on Cancer
      (AJCC). Staging is done with the assistance of endorectal ultrasound, which is
      best used in early-stage cancer; however, there are certain disadvantages in
      detecting node involvement. Magnetic resonance, on the other hand, allows for the
      evaluation of stenotic tumors and node involvement. Once the correct diagnosis
      and staging have been made, the next step is correct treatment. Neoadjuvant
      treatment has demonstrated to be better than adjuvant treatment. Abdominoperineal
      resection is rarely practiced currently, with sphincter preservation being the
      preferred procedure. Laparoscopic approach has conferred the advantages of the
      approach itself when performed by experts in the procedure but there is
      insufficient evidence to make it the "gold standard." Rectal cancer is a complex
      pathology that must be considered totally different from colon cancer for
      diagnosis and treatment. The patient must be staged completely and appropriately
      for individualizing correct treatment. More long-term studies are needed for
      optimizing treatment modalities.

PMID- 22385772
TI  - Cytomegalovirus infection in early childhood may be protective against
      glioblastoma multiforme, while later infection is a risk factor.
AB  - Glioblastoma multiforme is the most common and most aggressive type of primary
      brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all
      intracranial tumors. Recently, evidence for a viral cause has been postulated,
      possibly cytomegalovirus (CMV). In one report, 80% of patients with newly
      diagnosed glioblastoma multiforme had detectable cytomegalovirus DNA in their
      peripheral blood, while sero-positive normal donors and other surgical patients
      did not exhibit detectable virus. However, another study reported that five
      glioblastoma patients showed no circulating CMV detected either with RT-PCR or
      blood culture. But CMV could still be a factor in the genesis of glioblastoma
      multiforme, if age at infection is taken into account, since the incidence of
      both glioblastoma multiforme and CMV infection are inversely related to
      socioeconomic status. CMV infection in early childhood, more common in lower
      socioeconomic groups, may be protective against glioblastoma multiforme, whereas
      CMV infection in later childhood or adulthood may be a risk factor for
      glioblastoma. If so, glioblastoma multiforme occurrence would resemble paralytic
      polio, where low socioeconomic status, poor hygiene and early infection are
      protective.

PMID- 22385773
TI  - Index metacarpal fracture after tightrope suspension following trapeziectomy:
      case report.
AB  - Trapeziectomy, by itself or combined with ligament reconstruction/interposition
      arthroplasty, is commonly performed for advanced trapezial-metacarpal arthritis.
      Several methods and materials, both autogenous and artificial, are commonly used
      for ligament reconstruction and interposition arthroplasty. Harvesting autologous
      tendons adds to operative time and could increase potential surgical
      complications. Using an artificial material would, in theory, avoid some of these
      problems. However, this approach is not without its problems. We present a case
      of index metacarpal fracture after using the Arthrex Mini TightRope (Arthrex,
      Naples, FL) suture button fixation of the thumb and index metacarpals after
      complete trapeziectomy.

PMID- 22385774
TI  - Staged external fixation for chronic fracture-dislocation of the proximal
      interphalangeal joint: outcomes of patients with a minimum 2-year follow-up.
AB  - PURPOSE: To introduce a new surgical strategy for chronic fracture-dislocations
      of the proximal interphalangeal (PIP) joint with 2-staged external fixation. We
      also assessed the results of this method in all of our patients with at least 2
      years of follow-up. METHODS: We used the procedure in 6 cases. For the first
      step, we applied mini external fixators for 1 week before surgery to apply
      traction to the PIP joint with sufficient force to stretch the dislocated joint
      components. The second procedure was surgical release of the PIP joint and an
      attempt at percutaneous reduction and fixation. This was not possible in 4 cases,
      and we performed an open reduction and corrective osteotomy. Postoperative early
      rehabilitation was achieved under controlled movement using an external fixator
      that allowed PIP joint flexion and extension. RESULTS: At long-term follow-up
      (mean, 3.5 y), the range of movement of PIP joints had increased by 76 degrees ,
      and that of distal interphalangeal joints by 35 degrees . Osteochondral
      remodeling likely occurred not only while the joint was protected with the
      dynamic external fixator during a 12-week period (range, 8-14 wk), but also after
      removal. CONCLUSIONS: Preoperative traction softens the PIP joint, facilitating
      both surgery and rehabilitation. Postoperative early exercise with controlled
      movement, while maintaining concentric reduction with the external fixator, may
      accelerate osteochondral repair of the injured PIP joint.

PMID- 22385775
TI  - Scaphoid excision and midcarpal arthrodesis: the effect of triquetral excision--a
      biomechanical study.
AB  - PURPOSE: To evaluate the biomechanical alterations that occur after traditional
      scaphoid excision and midcarpal arthrodesis with and without excision of the
      triquetrum. The hypothesis of this study was that removal of the triquetrum
      increases the radiolunate contact pressure. METHODS: We cyclically moved 10 fresh
      cadaver wrists using a wrist joint motion simulator while measuring the contact
      pressures between the proximal carpal row and the distal radius and ulna using a
      dynamic pressure sensor. We acquired data in the intact wrist, after a midcarpal
      arthrodesis with the scaphoid excised, and then again with the triquetrum
      removed, which is also known as a capitolunate arthrodesis. RESULTS: The peak
      pressures in the radiolunate fossa significantly increased with either of the
      midcarpal arthrodeses compared with the intact wrist during each of the 3 dynamic
      wrist motions. In comparing the 2 midcarpal arthrodeses, the peak pressure in the
      ulnocarpal fossa significantly decreased after the triquetrum was removed during
      wrist radioulnar deviation and in the static ulnarly deviated position. After
      arthrodesis, we could identify no differences during any motion or static wrist
      position in the peak radiolunate pressures with or without the triquetrum.
      CONCLUSIONS: We found that scaphoid excision and 4-corner arthrodesis shifts
      loads to the radiolunate joint. Isolated capitolunate arthrodesis with excision
      of the scaphoid and triquetrum further alters carpal kinematics and loading
      patterns. CLINICAL RELEVANCE: These findings raise concern about routine excision
      of the triquetrum when performing a midcarpal arthrodesis.

PMID- 22385776
TI  - Immobilization in supination versus neutral following surgical treatment of
      Galeazzi fracture-dislocations in adults: case series.
AB  - PURPOSE: The goal of this study was to investigate whether immobilization in
      supination is necessary to prevent recurrent distal radioulnar joint (DRUJ)
      instability in patients older than 18 years with a Galeazzi fracture-dislocation
      and a stable DRUJ following open reduction and internal fixation of the radius.
      METHODS: We performed a retrospective chart review of 10 consecutive patients who
      were immobilized in either supination or a neutral position following surgical
      treatment of a Galeazzi fracture-dislocation in which the DRUJ was noted to be
      stable immediately after fixation of the radius. Group 1 consisted of 5 patients
      who were immobilized in supination for a period of 4 weeks, and group 2 consisted
      of 5 patients who were immobilized in neutral for 2 weeks, followed by functional
      bracing. RESULTS: Patients were followed up for an average of 68 months (range,
      26-124 mo) after surgery. No significant difference was noted between the 2
      groups with respect to age, medical comorbidities (no noteworthy medical
      comorbidities in either group), or hand dominance. None of the patients in either
      group demonstrated DRUJ instability during the follow-up period or required any
      additional surgery. At the latest follow-up, patients in the 2 groups had
      comparable forearm motion. CONCLUSIONS: The results of the current study suggest
      that following open reduction and internal fixation of the radius in patients
      with Galeazzi fracture-dislocations and with stable DRUJs, immobilization in
      supination for 4 weeks does not have an advantage over immobilization in neutral
      for a shorter period.

PMID- 22385778
TI  - Additional considerations in complex regional pain syndrome.

PMID- 22385779
TI  - The epidemiology of bovine spongiform encephalopathy in the Republic of Ireland
      before and after the reinforced feed ban.
AB  - Bovine spongiform encephalopathy (BSE) is a prion disease spread by the inclusion
      in cattle feed of meat and bone meal made from cattle infected with the BSE
      agent. In the Republic of Ireland, a reinforced feed ban on mammalian meat and
      bone meal (MMBM) was introduced on 17th October 1996 to stop further infection of
      cattle. Between then and July 2010, 44 cases of BSE from 40 herds have been born,
      termed "born after the reinforced ban" or "BARB" cases. The objectives of this
      project were: (a) to describe the epidemiology of these BARB cases, (b) to
      determine area-level risk factors for BSE herds and how they related to the stage
      of the BSE epidemic, and (c) to evaluate whether the spatial pattern of BSE cases
      was non-random and had changed over time. The BSE epidemic was divided into three
      phases: cases born prior to 1991, born 1991-October 1996 and BARB cases. To
      determine the area level risk factors for BSE herds, a case-control study was
      conducted for each phase of the epidemic. We selected four control herds for each
      herd with one or more BSE cases. A grid of hexagons of 10 km diameter was created
      covering the territory of the Republic of Ireland and BSE herds and control herds
      were assigned to a hexagon. The numbers of cattle herds, dairy herds, piggeries
      and poultry holdings within the hexagons containing these case and control herds
      were enumerated. To evaluate the spatial pattern of BSE cases, standardised
      mortality ratios were calculated for each hexagon, and Oden's Ipop was used to
      investigate clustering. The descriptive analysis showed "feeding of concentrates"
      as the only common factor to all BARB cases for which information existed. The
      case-control study identified being a dairy herd as a risk factor during the pre
      1991 phase of the BSE epidemic. Dairy herd type, a large proportion of local
      herds which were dairy and large numbers of piggeries and poultry holdings
      locally were also risk factors during the 1991-1996 phase. For the post-October
      1996 phase (BARBs), dairy herd type and large numbers of other herds locally were
      risk factors. The spatial pattern of BSE cases changed over the three phases of
      the epidemic and was non-random, with evidence of clustering. The evidence
      supports the hypothesis that BARB cases do not arise spontaneously but rather are
      caused by the same food-borne infectious route as other BSE cases.

PMID- 22385780
TI  - Factors associated with failure in breeding soundness examination of Western USA
      rams.
AB  - Breeding-soundness examination (BSE) and eradication of Brucella ovis infection
      in rams are critical components of flock-health programs. The aims of this
      retrospective, cross-sectional study were to describe the results of BSE in a
      large sample of rams in the Western USA and to determine the association between
      BSE outcome and the semen collection method (penis manually extended vs. retained
      in the preputial cavity), ram body-condition score (BCS), the presence of
      ulcerative posthitis, and the size of the flock of origin. We evaluated the first
      BSE in a given year for rams from Colorado, Wyoming, and Utah, USA, from 2000
      through 2007. Breeding-soundness examination consisted of physical examination,
      scrotal circumference and BCS measurement, semen collection by
      electroejaculation, and microscopic examination of semen motility, morphology,
      and leukocyte concentration. We assigned a reason for failure to each failed BSE
      and used multivariable logistic and Poisson regressions to measure associations
      between ram and flock variables and the risk or reason for failure on BSE. A non
      random, owner-selected subset of rams was tested for antibodies to B. ovis by
      serum indirect ELISA (iELISA). The Rogan-Gladen corrected B. ovis seroprevalence
      was measured. Of the 14,667 BSEs performed on 11,804 rams, 29.0% were classified
      as "failed;" the most common reason for failure was substandard semen parameters
      (43.8%). Breeding-soundness examinations were more likely to have been
      categorized as failure for inflammatory causes when performed on rams from medium
      sized flocks (OR 1.6; 95% CI 1.1, 2.3) and large flocks (OR 1.4; 95% CI 1.0, 1.9)
      (P=0.02), suggesting that larger flocks are at higher risk of contagious
      diseases. The adjusted seroprevalence of B. ovis antibodies among tested rams in
      this study was 10.0%. Of 233 rams seropositive to B. ovis, 125 (53.6%) were
      subclinical, a finding that supports the importance of this test in ram BSE. We
      found that emaciation in rams was associated with an increased risk of BSE
      failure from substandard semen parameters (P<0.001), but ulcerative posthitis and
      the semen collection method were not (P=0.09 and 0.34, respectively). However,
      collection of semen with the penis retained in the preputial cavity resulted in
      greater odds of leukospermia relative to semen collection with the penis extended
      (OR 4.1; 95% CI 2.9, 5.9; P<0.001), presumably from contamination of the semen
      sample with preputial leukocytes. For ram BSE, therefore, semen collection with
      the penis manually extended from the sheath is recommended to limit leukocyte
      contamination of the sample.

PMID- 22385781
TI  - Phosphate binder use and mortality among hemodialysis patients in the Dialysis
      Outcomes and Practice Patterns Study (DOPPS): evaluation of possible confounding
      by nutritional status.
AB  - BACKGROUND: Poor nutritional status and both hyper- and hypophosphatemia are
      associated with increased mortality in maintenance hemodialysis (HD) patients. We
      assessed associations of phosphate binder prescription with survival and
      indicators of nutritional status in maintenance HD patients. STUDY DESIGN:
      Prospective cohort study (DOPPS [Dialysis Outcomes and Practice Patterns Study]),
      1996-2008. SETTING & PARTICIPANTS: 23,898 maintenance HD patients at 923
      facilities in 12 countries. PREDICTORS: Patient-level phosphate binder
      prescription and case-mix-adjusted facility percentage of phosphate binder
      prescription using an instrumental-variable analysis. OUTCOME: All-cause
      mortality. RESULTS: Overall, 88% of patients were prescribed phosphate binders.
      Distributions of age, comorbid conditions, and other characteristics showed small
      differences between facilities with higher and lower percentages of phosphate
      binder prescription. Patient-level phosphate binder prescription was associated
      strongly at baseline with indicators of better nutrition, ie, higher values for
      serum creatinine, albumin, normalized protein catabolic rate, and body mass index
      and absence of cachectic appearance. Overall, patients prescribed phosphate
      binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for
      serum phosphorus level and other covariates; further adjustment for nutritional
      indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However,
      this inverse association was observed for only patients with serum phosphorus
      levels >=3.5 mg/dL. In the instrumental-variable analysis, case-mix-adjusted
      facility percentage of phosphate binder prescription (range, 23%-100%) was
      associated positively with better nutritional status and inversely with mortality
      (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment
      for nutritional indicators reduced this association to an HR of 0.95 (95% CI,
      0.92-0.99). LIMITATIONS: Results were based on phosphate binder prescription;
      phosphate binder and nutritional data were cross-sectional; dietary restriction
      was not assessed; observational design limits causal inference due to possible
      residual confounding. CONCLUSIONS: Longer survival and better nutritional status
      were observed for maintenance HD patients prescribed phosphate binders and in
      facilities with a greater percentage of phosphate binder prescription.
      Understanding the mechanisms for explaining this effect and ruling out possible
      residual confounding require additional research.

PMID- 22385782
TI  - Motivational dynamics of eating regulation: a self-determination theory
      perspective.
AB  - Within Western society, many people have difficulties adequately regulating their
      eating behaviors and weight. Although the literature on eating regulation is
      vast, little attention has been given to motivational dynamics involved in eating
      regulation. Grounded in Self-Determination Theory (SDT), the present contribution
      aims to provide a motivational perspective on eating regulation. The role of
      satisfaction and thwarting of the basic psychological needs for autonomy,
      competence, and relatedness is introduced as a mechanism to (a) explain the
      etiology of body image concerns and disordered eating and (b) understand the
      optimal regulation of ongoing eating behavior for healthy weight maintenance. An
      overview of empirical studies on these two research lines is provided. In a final
      section, the potential relevance and value of SDT in relation to prevailing
      theoretical models in the domain of eating regulation is discussed. Although
      research on SDT in the domain of eating regulation is still in its early stages
      and more research is clearly needed, this review suggests that the SDT represents
      a promising framework to more thoroughly study and understand the motivational
      processes involved in eating regulation and associated problems.

PMID- 22385783
TI  - Minimizing inappropriate medications in older populations: a 10-step conceptual
      framework.
AB  - The increasing burden of harm resulting from the use of multiple drugs in older
      patient populations represents a major health problem in developed countries.
      Approximately 1 in 4 older patients admitted to hospitals are prescribed at least
      1 inappropriate medication, and up to 20% of all inpatient deaths are
      attributable to potentially preventable adverse drug reactions. To minimize this
      drug-related iatrogenesis, we propose a quality use of medicine framework that
      comprises 10 sequential steps: 1) ascertain all current medications; 2) identify
      patients at high risk of or experiencing adverse drug reactions; 3) estimate life
      expectancy in high-risk patients; 4) define overall care goals in the context of
      life expectancy; 5) define and confirm current indications for ongoing treatment;
      6) determine the time until benefit for disease-modifying medications; 7)
      estimate the magnitude of benefit versus harm in relation to each medication; 8)
      review the relative utility of different drugs; 9) identify drugs that may be
      discontinued; and 10) implement and monitor a drug minimization plan with ongoing
      reappraisal of drug utility and patient adherence by a single nominated
      clinician. The framework aims to reduce drug use in older patients to the minimum
      number of essential drugs, and its utility is demonstrated in reference to a
      hypothetic case study. Further studies are warranted in validating this framework
      as a means for assisting clinicians to make more appropriate prescribing
      decisions in at-risk older patients.

PMID- 22385784
TI  - Amiodarone-associated optic neuropathy: a critical review.
AB  - Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use
      is limited by serious toxicities, including optic neuropathy. Current reports of
      amiodarone-associated optic neuropathy identified from the Food and Drug
      Administration's Adverse Event Reporting System and published case reports were
      reviewed. A total of 296 reports were identified: 214 from the Adverse Event
      Reporting System, 59 from published case reports, and 23 from adverse events
      reports for patients enrolled in clinical trials. Mean duration of amiodarone
      therapy before vision loss was 9 months (range 1-84 months). Insidious onset of
      amiodarone-associated optic neuropathy (44%) was the most common presentation,
      and nearly one third were asymptomatic. Optic disk edema was present in 85% of
      cases. Following drug cessation, 58% had improved visual acuity, 21% were
      unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200)
      was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance
      of patients during the tenure of amiodarone administration is warranted.

PMID- 22385786
TI  - Clinical neuropathology practice news 2-2012: BRAF V600E testing.
AB  - Activating mutations of the serine threonine kinase v-RAF murine sarcoma viral
      oncogene homologue B1 (BRAF), most commonly of the V600E type, are found in a
      wide range of human neoplasms including primary and secondary brain tumors.
      Therapeutic BRAF inhibitors have shown clinically meaningful activity,
      particularly in metastatic BRAF V600E mutated melanoma including patients with
      brain metastases. Therefore, in current neuropathological practice BRAF testing
      is of clinical importance in tissue samples of melanoma brain metastases in order
      to identify cases amenable to therapy with BRAF inhibitors. BRAF mutation testing
      may also add additional information for differential diagnosis of primary brain
      tumors in selected situations, e.g., for differentiation of anaplastic
      pleomorphic xanthoastrocytoma (BRAF V600E mutation in 65%) from glioblastoma
      (BRAF V600E mutation in < 5%). The BRAF mutation status can be tested with DNA
      based methods and immunohistochemistry using a V600E mutation-specific antibody.
      In summary, at this point BRAF V600E testing is clinically indicated in
      relatively few cases of the daily clinical neuropathology practice, but has
      important predictive implications for patients with melanoma brain metastases.
      Depending on the results of additional clinical studies, determination of BRAF
      mutation status may become clinically relevant also for primary brain tumors such
      as glioblastoma in the future.

PMID- 22385787
TI  - Pathologic diversity of glioneuronal tumor with neuropil-like islands: a
      histological and immunohistochemical study with a special reference to isocitrate
      dehydrogenase 1 (IDH1) in 5 cases.
AB  - Glioneuronal tumor with neuropil-like islands (GTNI) is featured by "neuropil
      like islands (NIs)" within dominating astroglial components. Isocitrate
      dehydrogenase (IDH) mutations, particularly IDH1 R132H (G395A), are found in WHO
      Grade II and III diffuse gliomas as well as secondary, but not primary,
      glioblastomas. We reviewed 5 cases of GTNI, and assessed histology and
      immunohistochemistry with various antibodies, including those for IDH1 R132H, as
      well as direct DNA sequencing for IDH1 G395A. NIs were variable in morphology,
      and constantly synaptophysin-positive and glial fibrillary acidic protein
      negative. The glioma components were primary glioblastoma in 2 cases, anaplastic
      astrocytoma in 1 and anaplastic oligoastrocytoma in 2. The IDH1 R132H was
      expressed in the 2 cases with oligoastrocytoma: In 1, NIs and the astrocytoma
      like area as well as the oligodendroglioma-like area were positive. In the other,
      only the oligodendrogliomalike area was positive. The mutation analysis performed
      on the latter case with DNA separately sampled from the oligodendroglioma- like
      area and the astrocytoma-like area detected IDH1 G395A in both areas. We have
      shown diverse pathologic aspects of GTNI. Also, we have shown that the expression
      of IDH1 R132H in GTNI is largely concordant with that in diffuse gliomas, and
      that it can be dependent on each histologic component although the mutant IDH1
      gene is ubiquitously present within the tumor.

PMID- 22385788
TI  - Bilateral non-contiguous atypical papillary glioneuronal tumor: case report.
AB  - Papillary glioneuronal tumor (PGNT) was first described as a distinct clinic
      pathological entity by Komori et al. in 1998. Since then it has been included as
      a mixed neuronal-glial tumor in the revised WHO (2007) classification of central
      nervous system tumors. On brain imaging, it appears as a demarcated, solid to
      cystic, contrast-enhancing mass usually located in the temporal lobe.
      Histologically, it is considered a biphasic tumor characterized by small cuboidal
      GFAP-positive astrocytes around hyalinised blood vessels and synaptophysin
      positive interpapillary collections of neurocytes, large neurons and intermediate
      sized "ganglioid cells". Although they are generally regarded as benign WHO Grade
      I tumors, recent reports have described more pathologically aggressive features.
      To date, these reports have all been single lesions.

PMID- 22385789
TI  - Non-necrotizing autoimmune myopathy with pipestem type capillaries - a light and
      electron microscopic study.
AB  - We report on 7 cases of a nonnecrotizing type of autoimmune myopathy found in
      suspected connective tissue disease and related disorders. In muscle biopsy,
      these cases showed myopathic alterations characterized by irregular outlines of
      muscle fibers in cross and longitudinal section nearly or totally lacking
      inflammatory cell infiltrations or macrophages and no necroses of myofibers. They
      revealed deposition of immunoglobulins and of collagen IV antibodies attached to
      fiber surface. The number of capillaries per myofiber was enlarged. Capillaries
      of pipestem type with thickened wall were found at the electron microscopic
      level. This type of myopathy was seen especially in subacute cases presenting
      with muscle pain, weakness and increased unspecific inflammatory laboratory
      parameters. No evidence for polymyositis, dermatomyositis or inclusion body
      myositis could be found. In all cases, steroid therapy was of striking benefit.

PMID- 22385790
TI  - Neuropathology and general autopsy findings in nondemented aged subjects.
AB  - A retrospective study of the essential general pathology and neuropathological
      features in 100 nondemented individuals aged 65 years or older (mean 81.23 +/-
      5.47 y) was performed using semiquantitative methods. 91% of the patients had a
      history of hypertension, 31% malignancies, 24% COPD, 18% myocardial infarction,
      and 4% stroke. Major causes of death were cardiovascular decompensation,
      pneumonia, acute myocardial infarction, and malignancies. General autopsy
      revealed severe systemic and coronary atherosclerosis in 86 and 90%,
      respectively, renal angioangiolosclerosis in 82%, acute or recurrent myocardial
      infarction in 65%, and other diseases. Neuropathology showed average brain weight
      of 1,163 +/- 113 g, mild to moderate brain atrophy, absent to mild
      atherosclerosis of large cerebral arteries in 46%, mild, moderate and severe one
      in 31, 17, and 6%, respectively. There were considerable discrepancies in the
      severity between generalized/ aortic and intracranial atherosclerosis, only less
      than one-third being comparable. Negative Khachaturian criteria and CERAD Stage 0
      were observed in 83 and 86%, respectively, only 13% with CERAD Stage A, and 1%
      Stage B. Braak neuritic stages ranged from 0 to II (53%), II - III (29%) to III -
      IV (18%), none scoring Grade V or VI. The average Braak score was 2.3 +/- 0.8.
      Vascular pathologies were common; CAA was absent in 61%, mild or moderate in 36%
      and severe in 3%. Mild to severe lacunar state in basal ganglia and/or white
      matter was seen in 73%, hippocampal sclerosis in 3 cases, while only 9% were free
      of cerebrovascular lesions. Lewy bodies were observed in 5 brains involving
      substantia nigra (n = 3), cerebral cortex (n = 1) and medulla oblongata (n = 1),
      1 case representing incidental Lewy body disease. tau pathology in brainstem was
      observed in 60 cases (60%). Mixed cerebral pathologies (cerebrovascular lesions
      and moderate neuritic Braak stages) were observed in 6 cases (mean age 89.6 y).
      The importance of mixed pathologies in nondemented elderly, being less frequent
      than in other studies, remains to be elucidated.

PMID- 22385791
TI  - Incongruous differential immunoexpression of the MGMT protein in a double adenoma
      of the pituitary with homogeneous nonmethylated MGMT promoter genotype.

PMID- 22385792
TI  - Granular cell tumor of the trigeminal nerve.

PMID- 22385794
TI  - Effect of high hydrostatic pressure on the color and texture parameters of
      refrigerated Caiman (Caiman crocodilus yacare) tail meat.
AB  - The effect of applying high hydrostatic pressure (HHP) on the instrumental
      parameters of color and texture and sensory characteristics of alligator meat
      were evaluated. Samples of alligator tail meat were sliced, vacuum-packed,
      pressurized and distributed into four groups: control, treated with 200 MPa/10
      min, 300 MPa/10 min and 400 MPa/10 min, then stored at 4 degrees C+/-1 degrees C
      for 45 days. Instrumental color, texture profile and a sensory profiling using
      quantitative descriptive analysis were carried out on the 1st, 15th, 30th and
      45th days of storage. HHP was shown to affect the color and texture of the
      product, and the sensory descriptors (p<0.05). The results suggest that high
      pressure is a promising technology for the processing of alligator meat,
      especially low pressures (200 MPa) which can have positive effects on the quality
      of the product.

PMID- 22385795
TI  - Dosimetric predictors of chest wall pain after lung stereotactic body
      radiotherapy.
AB  - PURPOSE: To identify risk factors for the development of chest wall (CW) pain
      after thoracic stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A
      registry of patients with lung lesions treated with lung SBRT was explored to
      identify patients treated with 54 Gy in three fractions or 50 Gy in five
      fractions. One hundred and forty-six lesions in 140 patients were identified;
      complete electronic treatment plans were available on 86 CWs. The CW was
      contoured as a 3 cm outward expansion from the involved lung. Univariate and
      multivariate analyses were used to correlate patient, tumor, and dosimetric
      factors to the development of CW toxicity. RESULTS: CW pain occurred in 22
      patients (15.7%). The Kaplan-Meier estimated risk of CW pain at 2 years was 20.1%
      (95% C.I., 13.2-28.8%). On univariate analysis of patient factors, elevated BMI
      (p=0.026) and connective tissue disease (p=0.036) correlated with CW pain. The
      percent of CW receiving 30, 35, or 40 Gy was most predictive of CW pain on
      multivariate analysis using logistic regression, while V40 alone was predictive
      using Cox regression. A V30 threshold of 0.7% and V40 threshold of 0.19% was
      correlated with a 15% risk of CW pain. CONCLUSIONS: We have described patient and
      dosimetric parameters that correlate with CW pain after lung SBRT. The risk of CW
      pain may be mitigated by attempting to reduce the relative proportion of CW
      receiving 30-40 Gy during treatment planning.

PMID- 22385796
TI  - TGFbeta1 SNPs and radio-induced toxicity in prostate cancer patients.
AB  - BACKGROUND AND PURPOSE: We have performed a case-control study in 413 prostate
      cancer patients to test for association between TGFbeta1 and the development of
      late normal-tissue toxicity among prostate cancer patients treated with three
      dimensional conformational radiotherapy (3D-CRT) MATERIALS AND METHODS: Late
      gastrointestinal and genitourinary toxicities were assessed for at least two
      years after radiotherapy in 413 patients according to CTCAEvs3 scores. Codominant
      genotypic tests and haplotypic analyses were undertaken to evaluate the
      correlation between TGFbeta1 SNPs rs1800469, rs1800470 and rs1800472 and radio
      induced toxicity. RESULTS: Neither the SNPs nor the haplotypes were found to be
      associated with the risk of late toxicity. CONCLUSIONS: We were able to exclude
      up to a 2-fold increase in the risk of developing late gastrointestinal and
      genitourinary radio-induced toxicity due to the TGFbeta1 SNPs rs1800469 and
      rs1800470, as well as the two most frequent TGFbeta1 haplotypes.

PMID- 22385797
TI  - Effect of smoking on oxygen delivery and outcome in patients treated with
      radiotherapy for head and neck squamous cell carcinoma--a prospective study.
AB  - BACKGROUND: Head and neck cancer patients with high hemoglobin respond better to
      irradiation compared to patients with low hemoglobin possibly due to hypoxia
      induced radioresistance. The hemoglobin level is, however, a crude indicator of
      the amount of oxygen available to the tissue and may be influenced by a number of
      factors, smoking being of potential importance. The aim of the present study was
      to examine the effect of smoking on available oxygen to tumors and the effect on
      outcome in head and neck cancer patients treated with radiotherapy in a
      prospective study. MATERIALS AND METHODS: A total of 232 consecutive patients
      with squamous cell carcinoma of the larynx, pharynx and oral cavity completed
      questionnaires on smoking habits prior to treatment. Venous blood samples were
      collected before and/or during treatment to determine the hemoglobin and
      carboxyhemoglobin level. Patients were treated with primary curative radiotherapy
      62-68 Gy, 2 Gy/fx, 5 fx/week. RESULTS: All but 12 patients had a history of
      smoking, 35 were long term quitters, 23 recent quitters, 54 moderate smokers and
      108 heavy smokers (>1 pack/day). There was no relationship between total
      hemoglobin and carboxyhemoglobin, but effective hemoglobin and carboxyhemoglobin
      were linearly correlated. The amount of carboxyhemoglobin increased with
      increasing smoking status. Actuarial 5-year univariate analysis showed that heavy
      smokers had a significantly reduced probability of loco-regional control (44% vs.
      65%, p = 0.001), disease-specific (56% vs. 77%, p = 0.003) and overall survival
      (39% vs. 66%, p = 0.0004) compared to non-smoking patients. Multivariate analyses
      showed that patients characterized as non-smokers, with low T and N
      classifications and high hemoglobin level had the best outcome measurements. A
      rise in carboxyhemoglobin significantly decreased the probability of loco
      regional control and each additional pack year increased the risk of death.
      Smokers and former smokers develop secondary cancers. CONCLUSION: The study
      showed a significant negative impact of smoking during radiotherapy for head and
      neck cancer and the risk of death was increased with each additional pack year of
      smoking. The effect on loco-regional control could be explained by a rise in
      carboxyhemoglobin level in smokers, e.g. a reduced oxygen supply to tumors. The
      data strongly advocate that smoking should be avoided in order to improve the
      therapeutic efficacy of radiotherapy and development of other smoking-related
      diseases and/or secondary cancers.

PMID- 22385798
TI  - "Whole brain radiotherapy: are parotid glands organs at risk?".

PMID- 22385799
TI  - [Haemophilia A and intracranial bleedings in infants].
AB  - BACKGROUND AND PURPOSE: Haemophilia is a well-known X-linked recessive bleeding
      disorder related to a deficiency of factor VIII. The aim of the paper is to point
      out the role of an early diagnosis in cases of intracranial bleeding, especially
      in neonates and to highlight the bad prognosis. METHODS: Three patients were
      included in the study from our prospective data. All had severe factor VIII
      deficiency (less than 1%). RESULTS: The first of them was a newborn without
      familial history of haemophilia which presented with hypotonia and seizures after
      a delivery with vacuum. CT showed a subdural haematoma and MRI multiple ischemic
      lesions. Two months later, he died from a new intracranial haemorrhagic episode
      resistent to infusion of factor VIII related to development of an anti-factor
      VIII antiboby. The second neonate had no familial history more and experienced
      hypothermia and areactive mydriasis because of an acute subdural haematoma. He
      died eight days later of ischemic lesions in spite of a craniotomy. The third was
      a 5-month-old boy with a familial history. Physical examination revealed
      lethargy, seizure and a recent cranial perimeter increase. He underwent a
      craniotomy with a good result. CONCLUSION: The authors stress the need for
      immediate factor VIII infusion and appropriate neurosurgical work-up. The rapid
      medical management is mandatory if morbidity and mortality are to be minimized.

PMID- 22385801
TI  - Epidemiology of pediatric primary tumors of the nervous system: a retrospective
      study of 633 cases from a single Moroccan institution.
AB  - BACKGROUND AND PURPOSE: There are several reports regarding the epidemiology of
      pediatric brain tumors. However, little is known about the profile of pediatric
      brain tumors in Africa especially in Morocco in particular. The authors report
      the results of epidemiological analysis of a retrospective review of childhood
      primary brain tumors in a single institution. METHODS: A retrospective review of
      all cases of primary brain from 1 month to 15 years diagnosed at the Department
      of Pathology of the Hospital of Specialities of Rabat between January 1991 and
      December 2009 was performed. RESULTS: Six hundred and thirty-three primary tumors
      of the central nervous system were reviewed with a mean of 33.31 cases per year.
      According to the gender, 55% of the tumors occurred in males and 45% in females.
      The mean age was 8.36 years. Of all the tumors, 47% were situated in the
      supratentorial compartment, 48% in the infratentorial compartment, and 5% in
      spinal cord. In the infratentorial compartment, 82% of tumors are located in the
      cerebellum, 15% in the fourth ventricle, 2% in the brain stem and 1% in the
      cerebellar pontine angle. In the supratentorial compartment, two third of the
      tumors were located in the cerebral hemispheres and the sellar region. Thus 39%
      of tumors are located in the cerebral hemispheres followed by the
      sellar/suprasellar region (30%), lateral and third ventricles (11%), pineal
      region (8%), meninges (5%), choroid plexus (4%), and optic chiasma/tracts (3%).
      The most common types of tumors diagnosed were pilocytic astrocytoma and
      medulloblastoma together accounting for nearly half of the cases (46%) (23.1% and
      22.9% respectively), followed by craniopharyngiomas (9%), ependymomas grade II
      (6.5%), glioblastomas (6%), astrocytomas grade II (4.4%), ependymomas grade III
      (3.9%). The other tumors represent 22.6%. CONCLUSION: We think that our results
      reflect fairly well the incidence of tumors of the nervous system in children due
      to the fact that this study was performed through many years in a single
      institution with a homogeneous neuropathological approach.

PMID- 22385802
TI  - Analysis of olive allergens.
AB  - Olive pollen is one of the most important causes of seasonal respiratory allergy
      in Mediterranean countries, where this tree is intensely cultivated. Besides
      this, some cases of contact dermatitis and food allergy to the olive fruit and
      olive oil have been also described. Several scientific studies dealing with olive
      allergens has been reported, being the information available about them
      constantly increasing. Up to date, twelve allergens have been identified in olive
      pollen while just one allergen has been identified in olive fruit. This review
      article describes considerations about allergen extraction and production, also
      describing the different methodologies employed in the physicochemical and
      immunological characterization of olive allergens. Finally, a revision of the
      most relevant studies in the analysis of both olive pollen and olive fruit
      allergens is carried out.

PMID- 22385803
TI  - A Bayesian approach for application to method validation and measurement
      uncertainty.
AB  - The aim of this paper is to apply a new technique for the validation of
      quantitative analytical procedures based on Bayesian simulation and accuracy
      profile. Also, an original strategy for estimating measurement uncertainty by the
      same approach has been developed. The performance of our proposal was confirmed
      by application to analytical and bio-analytical methods. Compared to the
      classical strategy, the new approach has a more holistic character. It means that
      it is no longer necessary to know the various individual steps into which the
      analytical method can be broken down since this latter is taken as a whole.
      Furthermore, the Bayesian accuracy profile procedure allows to control the risk
      associated with the future use of the analytical method.

PMID- 22385804
TI  - A novel in-line NIR spectroscopy application for the monitoring of tablet film
      coating in an industrial scale process.
AB  - Film coating of tablets is a multivariate pharmaceutical unit operation. In this
      study an innovative in-line Fourier-Transform Near-Infrared Spectroscopy (FT
      NIRS) application is described which enables real-time monitoring of a full
      industrial scale pan coating process of heart-shaped tablets. The tablets were
      coated with a thin hydroxypropyl methylcellulose (HPMC) film of up to approx. 28
      MUm on the tablet face as determined by SEM, corresponding to a weight gain of
      2.26%. For a better understanding of the aqueous coating process the NIR probe
      was positioned inside the rotating tablet bed. Five full scale experimental runs
      have been performed to evaluate the impact of process variables such as pan
      rotation, exhaust air temperature, spray rate and pan load and elaborate robust
      and selective quantitative calibration models for the real-time determination of
      both coating growth and tablet moisture content. Principal Component (PC) score
      plots allowed each coating step, namely preheating, spraying and drying to be
      distinguished and the dominating factors and their spectral effects to be
      identified (e.g. temperature, moisture, coating growth, change of tablet bed
      density, and core/coat interactions). The distinct separation of HPMC coating
      growth and tablet moisture in different PCs enabled a real-time in-line
      monitoring of both attributes. A PLS calibration model based on Karl Fischer
      reference values allowed the tablet moisture trajectory to be determined
      throughout the entire coating process. A 1-latent variable iPLS weight gain
      calibration model with calibration samples from process stages dominated by the
      coating growth (i.e. >= 30% of the theoretically applied amount of coating) was
      sufficiently selective and accurate to predict the progress of the thin HPMC
      coating layer. At-line NIR Chemical Imaging (NIR-CI) in combination with PLS
      Discriminant Analysis (PLSDA) verified the HPMC coating growth and physical
      changes at the core/coat interface during the initial stages of the coating
      process. In addition, inter- and intra-tablet coating variability throughout the
      process could be assessed. These results clearly demonstrate that in-line NIRS
      and at-line NIR-CI can be applied as complimentary PAT tools to monitor a
      challenging pan coating process.

PMID- 22385805
TI  - High performance liquid chromatography for the simultaneous analysis of
      penicillin residues in beef and milk using ion-paired extraction and binary water
      acetonitrile mixture.
AB  - An ion-paired extraction (IPE) has been developed for the analysis of penicillin
      antibiotics (penicillin G, oxacillin and cloxacillin) in beef and milk samples
      using tetrabutylammonium bromide (TBABr) as ion-pairing agent and binary water
      acetonitrile as extractant. The factors affecting the IPE efficiency were
      optimized including solution pH, volume of acetonitrile (ACN), concentration of
      TBABr and electrolyte salt (NH(4))(2)SO(4). The optimum IPE conditions were 10
      mmol L(-1) phosphate buffer pH 8, 2 mL of ACN, 6 mmol L(-1) of TBABr and 2.5 mL
      of saturated ammonium sulfate. Under the HPLC condition: an XbridgeTM C18
      reversed-phase column, isocratic elution of 5 mmol L(-1) phosphate buffer (pH
      6.6) and acetonitrile (75:25, v/v) and a flow rate of 1 mL min(-1), with UV
      detection at 215 nm, the separation of three penicillins was achieved within 10
      min. Under the selected optimum conditions, the enhancement of 21-53 folds
      compared to that without preconcentration and limits of detection (LODs) of 1-2
      ng mL(-1) were obtained. Good reproducibility was achieved with RSD<2% for
      retention time and <5% for slope of calibration curves. The average recoveries
      higher than 85% were obtained. The proposed IPE-HPLC method has shown to be high
      efficient preconcentration and analysis method for penicillin residues in beef
      and milk with LOD lower than the maximum residue limits.

PMID- 22385806
TI  - The solvatochromic effects of side chain substitution on the binding interaction
      of novel tricarbocyanine dyes with human serum albumin.
AB  - The effects of solvatochromism on protein-ligand interactions have been studied
      by absorbance and near-infrared laser induced fluorescence (NIR-LIF)
      spectroscopy. The utility of three novel classes of cyanine dyes designed for
      this purpose illustrates that the affinity interactions of ligands at the
      hydrophobic binding pockets of Human Serum Albumin (HSA) are not only dependent
      on the overall hydrophobic characteristics of the molecules but are highly
      influenced by the size of the ligands as well. Whereas changes to the chromophore
      moiety exhibited slight to moderate changes to the hydrophobic nature of these
      molecules, substitution at the alkyl indolium side chain has enabled us to vary
      the binding affinity towards serum albumin. Substitution at the indolium side
      chain among an ethyl to butyl group results in improved binding characteristics
      and an almost three-fold increase in affinity constant. In addition, replacement
      of the ethyl side chain with a phenylpropyl group also yielded unique
      solvotachromic patterns such as increased hydrophobicity and subsequent
      biocompatibility with the HSA binding regions. Ligand interaction was however
      inhibited by steric hindrance associated with the bulky phenyl ring system thus
      affecting the increased binding that could be realized from the improved
      hydrophobic nature of the molecules. This characteristic change in binding
      affinity is of potential interest to developing a methodology which reveals
      information on the hydrophobic character and steric specificity of the binding
      cavities.

PMID- 22385807
TI  - Internal standardization combined with dilute-and-shoot preparation of distilled
      alcoholic beverages for Cu determination by high-resolution continuum source
      flame atomic absorption spectrometry.
AB  - Internal standardization (IS) and dilute-and-shoot preparation of distilled
      alcoholic beverages were evaluated for the direct determination of Cu by high
      resolution continuum source flame atomic absorption spectrometry. Among Bi, In,
      Sn and Te evaluated as internal standards, Bi and Te furnished best results.
      Calibration curves were built up by plotting A(Cu)/A(Bi) and A(Cu)/A(Te)versus Cu
      concentration (0.05-4.0 mg L(-1)) and linear correlation coefficients were 0.9994
      and 0.9990, respectively. Contents of Cu in 22 commercial distilled beverages
      analyzed by the proposed method varied in the 0.029-3.608 mg L(-1) interval.
      These results were in agreement (paired t-test) at 95% confidence level with
      those obtained by line source FAAS using standard addition calibration.
      Recoveries improved from 77-83% (without IS) to 99-101% (with IS) intervals. The
      relative standard deviation (n=12) was 0.8-3.7% (IS-Bi), 0.4-4.4% (IS-Te), and
      0.5-9.1% (without IS) and the limit of detection was ca. 5 MUg L(-1) using Bi or
      Te.

PMID- 22385808
TI  - Development and optimization of a novel conductometric bi-enzyme biosensor for L
      arginine determination.
AB  - A highly sensitive conductometric biosensor for l-arginine determination was
      developed by exploiting the unique biorecognition capacities of two enzymes of
      urea cycle - arginase (E.C. 3.5.3.1) and urease (E.C. 3.5.1.5). The enzymes were
      co-immobilized in a single bioselective membrane on the working sensor, while a
      lysine rich bovine serum albumin (BSA) membrane was immobilized on the reference
      sensor, allowing differential measurements. The optimum percentage ratio of
      arginase and urease within the bioselective membrane was determined when the
      biosensor sensitivity to l-arginine and urea was optimum. Analytical
      characteristics of the conductometric biosensor for l-arginine determination were
      compared for two types of enzyme immobilization (cross-linking with
      glutaraldehyde (GA) and entrapment in the polymeric membrane). The optimum
      features in terms of the sensitivity, the linear range, and the detection limit
      (4.2 MUS/mM, 0.01-4mM, and 5.0 * 10(-7)M, respectively) were found for l-arginine
      biosensor based on enzyme cross-linking with GA. A quantitative determination of
      l-arginine in the real sample (a drinkable solution "Arginine Veyron") gave a
      satisfactory result compared to the data provided by the producer (a relative
      error was 4.6%). The developed biosensor showed high operational and storage
      stability.

PMID- 22385809
TI  - A label-free aptasensor for the sensitive and specific detection of cocaine using
      supramolecular aptamer fragments/target complex by electrochemical impedance
      spectroscopy.
AB  - A simple and label-free aptasensor for sensitive and specific detection of
      cocaine was developed by measuring the change in electrochemical impedance
      spectra (EIS), based on the formation of a supramolecular aptamer
      fragments/substrate complex. An anticocaine aptamer was divided into two
      fragments, Cx and Cy. Three different sensing interfaces, called Au/Cx5S/MCE,
      Au/Cy3S/MCE and Au/Cy5S/MCE, were fabricated by immobilizing Cx or Cy on a gold
      electrode through modifying their 5' or 3' end with a thiolated group followed by
      the treatment with mercaptoethanol (MCE). The formation of the corresponding
      supramolecular aptamer fragments/cocaine complex was investigated via monitoring
      electrochemical impedance spectra in the presence of [Fe(CN)(6)](3-/4-). The
      interfacial electron transfer resistance (R(et)) was found to depend strongly on
      the cocaine concentration. Since the supramolecular aptamer fragments/cocaine
      complex was formed on the electrode surface, the sensing interface strongly
      affected the sensitivity of the aptasensor. Au/Cx5S/MCE was shown to have good
      sensitivity within a cocaine detection range of 0.1-20 MUM. Moreover, MCE was
      shown to improve the sensitivity of the aptasensor greatly. Even without the help
      of amplification or labeling, cocaine concentrations as low as 100 nM could be
      easily detected by the impedimetric aptasensor developed. The specificity and
      regeneration of the cocaine aptasensor were also investigated and satisfactory
      results were obtained. The developed aptasensor was successfully applied to
      detect the cocaine in biological fluids.

PMID- 22385810
TI  - Multiplexed detection of tumor markers with multicolor quantum dots based on
      fluorescence polarization immunoassay.
AB  - A multicolor quantum dot (QD)-based nanosensor for multiplex detection of two
      tumor markers in a homogeneous format based on fluorescence polarization
      immunoassay was proposed. QDs520 and QDs620 were labeled alpha-fetoprotein(alpha
      AFP) and carcinoembryonic antigen (CEA), respectively. After separated and
      purified by ultrafiltration, they were used in fluorescence polarization
      immunoassay for the simultaneous detection of human serum alpha-fetoprotein and
      carcinoembryonic antigen. Under the optimal conditions, the multi-analyte
      immunosensor had a wide linear range (from 0.5 ng mL(-1) to 500 ng mL(-1)) for
      both two tumor markers and good correlation (0.996 for alpha-AFP and 0.993 for
      CEA). The detection limits (LOD) were 0.36 ng mL(-1) for CEA and 0.28 ng mL(-1)
      for alpha-AFP (S/N=3). The carcinoembryonic antigen and fetoprotein in clinical
      serum samples were simultaneously detected. The results from 28 serum samples had
      a good agreement with enzyme-linked immunosorbent assay (ELISA). The relative
      standard deviation and the recovery suggested that the precision and the accuracy
      of this analytical method were satisfactory. This strategy with high sensitivity,
      good specificity, easy procedures and short analysis time shows great promise for
      clinical diagnoses and basic discovery. The application of QDs with longer
      fluorescence lifetime and small fluorescence polarization can be used for the
      determination of high molecular-weight substances which cannot be analyzed using
      dye fluorescence polarization immunoassay.

PMID- 22385811
TI  - A simple laser ablation ICPMS method for the determination of trace metals in a
      resin gel.
AB  - Trace metal analysis of DGT gels using laser ablation inductively coupled plasma
      (LA-ICP-MS) has traditionally been carried out by ablating single spots along a
      line to provide high resolution data on trace metal distributions on a resin gel.
      This work compares the performance of two different LA-ICPMS systems, one at
      Lancaster University, UK and another at VUB, Belgium, in terms of instrument
      sensitivity and limit of detection in the analysis of trace metals (Co, Ni, Cu,
      Zn, Cd, and Pb) bound by a DGT resin gel using SPR-IDA resin. No defocusing of
      the laser beam was necessary to prevent burning through the resin gel and the
      internal standardization became very simple by using (13)C, naturally present in
      the resin-gel, instead of impregnating a back-up layer with (115)In. Furthermore,
      this work also explores the option of analysing the spatial distribution of resin
      bound trace metals by means of ablating a continuous line between two points and
      considers the advantages of using this approach. The work found that the LODs
      assessed on blank samples for Cu and Pb are similar for both LA-ICPMS systems,
      while for Co, Ni and Zn they are lower for the one at VUB and for Cd for the
      other one at Lancaster. The work found that the laser ablation systems at the two
      laboratories allowed more precise control over laser power and spot size than
      previously reported. For the line scan, the optimum scan parameters were
      determined as: scan speed of 50 MUm s(-1), output energy of 40% and repetition
      rate of 30 Hz. An acquisition time of 25 ms, resulted in a much lower resolution
      (10 MUm) compared to the spot ablation (a crater size of 100 MUm and also some
      space between craters) and a better sensitivity. The LODs using the line scan
      were found to be lower than those obtained by the spot ablation. However, for
      some of the metals the difference is rather small. This work suggests that the
      time and gas consumption achieved by using the line scan is about 30% lower than
      for the traditional spot scan.

PMID- 22385812
TI  - Near-infrared spectrometric determination of dipyrone in closed ampoules.
AB  - The present paper proposes an analytical method for fast near-infrared (NIR)
      determination of dipyrone in injectable formulations with a nominal content of
      50.0%mv(-1) without violation of the ampoule. For this purpose, two multivariate
      calibration methods are evaluated, namely Partial-Least-Squares (PLS) and
      Multiple Linear Regression (MLR) with variable selection by the Successive
      Projections Algorithm (SPA). The resulting models comprised four latent variables
      (PLS) and five spectral variables (MLR-SPA). Appropriate predictions were
      obtained in both cases, with RMSEP values of 0.39 (PLS) and 0.35%mv(-1) (MLR-SPA)
      and correlation coefficients of 0.9970 (PLS) and 0.9975 (MLR-SPA) for a
      calibration range of 40-60%mv(-1). No systematic error was observed and no
      significant differences were found between the predicted and reference values,
      according to a paired t-test at 95% confidence level.

PMID- 22385813
TI  - Knowledge mobilisation in healthcare: a critical review of health sector and
      generic management literature.
AB  - The health policy domain has displayed increasing interest in questions of
      knowledge management and knowledge mobilisation within healthcare organisations.
      We analyse here the findings of a critical review of generic management and
      health-related literatures, covering the period 2000-2008. Using 29 pre-selected
      journals, supplemented by a search of selected electronic databases, we map
      twelve substantive domains classified into four broad groups: taxonomic and
      philosophical (e.g. different types of knowledge); theoretical discourse (e.g.
      critical organisational studies); disciplinary fields (e.g. organisational
      learning and Information Systems/Information Technology); and organisational
      processes and structures (e.g. organisational form). We explore cross-overs and
      gaps between these traditionally separate literature streams. We found that
      health sector literature has absorbed some generic concepts, notably Communities
      of Practice, but has not yet deployed the performance-oriented perspective of the
      Resource Based View (RBV) of the Firm. The generic literature uses healthcare
      sites to develop critical analyses of power and control in knowledge management,
      rooted in neo-Marxist/labour process and Foucauldian approaches. The review
      generates three theoretically grounded statements to inform future enquiry, by:
      (a) importing the RBV stream; (b) developing the critical organisational studies
      perspective further; and (c) exploring the theoretical argument that networks and
      other alternative organisational forms facilitate knowledge sharing.

PMID- 22385814
TI  - Addiction, agency, and the politics of self-control: doing harm reduction in a
      heroin users' group.
AB  - Our 2007-2009 ethnography describes and analyses the practice of harm reduction
      in a heroin users' group in the midwestern United States. While dominant
      addiction interventions conceptualize the addict as powerless - either through
      moral or physical weakness - this group contested such "commonsense," treating
      illicit drug use as one of many ways that modern individuals attempt to "fill the
      void." Insisting on the destigmatization of addiction and the normalization of
      illicit drug use, the group helped its members work on incremental steps toward
      self-management. Although "Connection Points" had very limited resources to
      improve the lives of its members, our work suggests that the users' group did
      much to restore self-respect, rational subjectivity, and autonomy to a group
      historically represented as incapable of reason and self-control. As the users
      cohered as a community, they developed a critique of the oppressions suffered by
      "junkies," discussed their rights and entitlements, and even planned the
      occasional political action. Engaging with literature on the cultural
      construction of agency and responsibility, we consider, but ultimately
      complicate, the conceptualization of needle exchange as a "neoliberal" form of
      population management. Within the context of the United States' War on Drugs, the
      group's work on destigmatization, health education, and the practice of
      incremental control showed the potential for reassertions of social citizenship
      within highly marginal spaces.

PMID- 22385815
TI  - Spatial modeling of households' knowledge about arsenic pollution in Bangladesh.
AB  - Arsenic in drinking water is an important public health issue in Bangladesh,
      which is affected by households' knowledge about arsenic threats from their
      drinking water. In this study, spatial statistical models were used to
      investigate the determinants and spatial dependence of households' knowledge
      about arsenic risk. The binary join matrix/binary contiguity matrix and inverse
      distance spatial weight matrix techniques are used to capture spatial dependence
      in the data. This analysis extends the spatial model by allowing spatial
      dependence to vary across divisions and regions. A positive spatial correlation
      was found in households' knowledge across neighboring districts at district,
      divisional and regional levels, but the strength of this spatial correlation
      varies considerably by spatial weight. Literacy rate, daily wage rate of
      agricultural labor, arsenic status, and percentage of red mark tube well usage in
      districts were found to contribute positively and significantly to households'
      knowledge. These findings have policy implications both at regional and national
      levels in mitigating the present arsenic crisis and to ensure arsenic-free water
      in Bangladesh.

PMID- 22385816
TI  - Mortality differences between the foreign-born and locally-born population in
      France (2004-2007).
AB  - In contrast to the situation in many European countries, the mortality of
      immigrants in France has been little studied. The main reasons for the lack of
      studies are based on ethical and ideological considerations. The objective of
      this study is to explore mortality by country of birth in Metropolitan (i.e.
      'mainland') France. Complete mortality data were used to study the relative risks
      of mortality of the foreign- and locally-born populations by gender, age and
      cause of death for the period 2004-2007 in Metropolitan France. Analyses were
      conducted by countries of birth grouped into geographic areas and by the Human
      Development Index (HDI). The differentials in mortality between foreign-born and
      locally-born populations were not homogeneous. The figures varied by age (higher
      foreign-born mortality for the young; lower mortality for migrants aged 15-64
      years), gender (female migrants more frequently had higher relative mortality
      than men migrants), country of birth (Eastern European-born migrants had higher
      mortality, while those born in Morocco, Central Asia, 'other Asian countries' and
      America had lower mortality) and cause of death (migrant mortality was higher
      overall for deaths caused by infectious diseases and diabetes, and lower for
      violent death and neoplasm). Moreover, mortality relative risks for male, violent
      deaths and cancer were positively associated with country-of-birth HDI, while
      female mortality and infectious disease mortality were negatively associated with
      country-of-birth HDI. Some important caveats have to be considered because the
      study did not control for individuals socioeconomic position in France, or length
      of residence in the host country. A strong healthy migrant effect was suggested
      and its intensity varies with age and gender (which may reflect different reasons
      for migration). For some specific causes of death, a lifestyle effect seems to
      explain mortality differentials. The associations between HDI and mortality show
      that mortality trends are partly related to the educational, sanitary and
      economic conditions of the country of birth. Further studies would enrich the
      differential analysis of mortality by country of birth by contributing additional
      detailed data on socioeconomic and living conditions in the host country as well
      as in the country of origin.

PMID- 22385817
TI  - Graphic warning labels on plain cigarette packs: will they make a difference to
      adolescents?
AB  - Graphic warning labels and plain cigarette packaging are two initiatives
      developed to increase quit behaviour among smokers. Although a little is known
      about how adolescents interpret graphic warning labels, very few studies have
      examined how plain cigarette packaging would affect adolescents' perceptions of
      cigarette smoking and smoking behaviour. We explored how teens interpret and
      respond to graphic warning labels and the plain packaging of cigarettes, to
      assess the potential these strategies may offer in deterring smoking initiation.
      Twelve focus group interviews with a sample of 80 14-16 year old students from a
      diverse range of schools in Auckland, New Zealand were undertaken between June
      and August 2009. Textual analysis revealed that graphic warning labels may
      influence adolescents by reiterating a negative image of smokers. Graphic warning
      on a plain cigarette pack increased the attention paid to graphic warning labels
      and the overall perceptions of harm caused by cigarette smoking, and reduced the
      social appeal of cigarette smoking. This research offers evidence on how
      adolescents are appraising and interpreting graphic warning labels, and explores
      how dominant appraisals may affect the role graphic warning labels play in
      preventing smoking. Not only would plain cigarette packaging enhance the salience
      and impact of graphic warning labels, but it would potentially bolster the
      overall message that cigarette smoking is harmful. In the context of a
      comprehensive tobacco control programme, graphic warning labels on plain
      cigarette packaging present an explicit message about the risks (to health and
      image) associated with cigarette smoking.

PMID- 22385818
TI  - Motivation, self-determination, and long-term weight control.
AB  - This article explores the topics of motivation and self-regulation in the context
      of weight management and related behaviors. We focus on the role of a qualitative
      approach to address motivation--not only considering the level but also type of
      motivation--in weight control and related behaviors. We critically discuss the
      operationalization of motivation in current weight control programs, present a
      complementary approach to understanding motivation based on self-determination
      theory, and review empirical findings from weight control studies that have used
      self-determination theory measures and assessed their association with weight
      outcomes. Weight loss studies which used Motivational Interviewing (MI) are also
      reviewed, considering MI's focus on enhancing internal motivation. We hypothesize
      that current weight control interventions may have been less successful with
      weight maintenance in part due to their relative disregard of qualitative
      dimensions of motivation, such as level of perceived autonomy, often resulting in
      a motivational disconnect between weight loss and weight-related behaviors. We
      suggest that if individuals fully endorse weight loss-related behavioral goals
      and feel not just competent but also autonomous about reaching them, as suggested
      by self-determination theory, their efforts are more likely to result in long
      lasting behavior change.

PMID- 22385819
TI  - Primary translocation of aberrant left subclavian artery for children with
      symptomatic vascular ring.
AB  - BACKGROUND: The standard operation for vascular ring with right aortic arch and
      aberrant left subclavian artery is ligamentum arteriosum division. A new surgical
      approach with primary translocation of the aberrant left subclavian artery to the
      left carotid artery, removal of the Kommerell diverticulum, and division of the
      ligamentum through left thoracotomy was recently applied. This study assessed the
      early outcomes of this approach. METHODS: This is a retrospective review of all
      patients having an operation for right aortic arch with aberrant left subclavian
      artery and the Kommerell diverticulum between January 2001 and April 2011 at a
      single institution. RESULTS: Eight patients had a division of the ligamentum and
      10 had a primary translocation of an aberrant left subclavian artery with
      diverticulum removal and ligamentum division. The median operative age and weight
      for each surgical technique group were, respectively, 2.2 and 1.8 years (p =
      0.56) and 10.7 and 12.6 kg (p = 0.30). All patients were symptomatic
      preoperatively. No deaths occurred. One patient from each group had chylous
      effusion that was medically treated. The median hospital stay for each group was
      4 and 5 days (p = 0.45). During the median follow-up of 47 months, 3 patients in
      the division of ligamentum group required albuterol aerosol or oral
      antiinflammatory medication for respiratory symptoms. All patients in the primary
      translocation group remained asymptomatic and required no medication (p = 0.069).
      CONCLUSIONS: Primary translocation of aberrant left subclavian artery with
      removal of the diverticulum and division of the ligamentum had excellent early
      outcomes and can potentially eliminate residual symptoms and late complications.

PMID- 22385800
TI  - [French brain tumor database: general results on 40,000 cases, main current
      applications and future prospects].
AB  - BACKGROUND AND PURPOSE: This work aimed at prospectively record all primary
      central nervous system tumor (PCNST) cases in France, for which histological
      diagnosis was available. The objectives were to (i) create a national database
      and network to perform epidemiological studies, (ii) implement clinical and basic
      research protocols, and (iii) harmonize the health care of patients affected by
      PCNST. METHODS: The methodology is based on a multidisciplinary national network
      already established by the French Brain Tumor DataBase (FBTDB) (Recensement
      national histologique des tumeurs primitives du systeme nerveux central
      [RnhTPSNC]), and the active participation of the Scientific Societies involved in
      neuro-oncology in France. RESULTS: From 2004 to 2009, 43,929 cases of newly
      diagnosed and histologically confirmed PCNST have been recorded. Histological
      diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%),
      tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and
      others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor
      resections were performed in 78% cases, while biopsies accounted for 22%. Median
      age at diagnosis, sex, percentage of resections and number of cryopreserved
      tumors were detailed for each histology, according to the WHO classification.
      DISCUSSION/CONCLUSION: Many current applications and perspectives for the FBTDB
      are illustrated in the discussion. To our knowledge, this work is the first
      database in Europe, dedicated to PCNST, including clinical, surgical and
      histological data (with also cryopreservation of the specimens), and which may
      have major epidemiological, clinical and research implications.

PMID- 22385820
TI  - Adult-derived Index for Mortality Prediction After Cardiac Transplantation
      (IMPACT) risk score predicts short-term mortality after pediatric heart
      transplantation.
AB  - BACKGROUND: We have previously derived and validated the Index for Mortality
      Prediction After Cardiac Transplantation (IMPACT), which predicts short-term
      mortality after adult orthotopic heart transplantation (OHT). This study
      evaluated the predictive accuracy of the IMPACT score in pediatric OHT. METHODS:
      The United Network for Organ Sharing registry was used to identify pediatric (<
      18 years) OHT patients from 2000 to 2008. The IMPACT score was calculated for
      each patient. The association of IMPACT score with 1-year mortality was evaluated
      with univariate and multivariable logistic regression analysis. The correlation
      coefficient between predicted and actual 1-year mortality was determined for each
      IMPACT score. Kaplan-Meier survival estimates were calculated and stratified by
      IMPACT score. RESULTS: We identified 2,518 eligible pediatric OHT patients (1,128
      girls [44.8%]). Mean IMPACT score was 10.3 +/- 6.3 (range, 0 to 38). A total of
      297 patients (11.8%) died within the first year after OHT. Each point increase in
      the IMPACT score increased the odds of 1-year mortality by 13% (odds ratio, 1.13;
      95% confidence interval, 1.11 to 1.15; p < 0.001). The correlation coefficient
      between predicted and actual 1-year mortality was 0.93 (p < 0.001). One-year
      survival by disjoint categories of the IMPACT score was 0 to 4 (96.7%), 5 to 9
      (92.9%), 10 to 14 (87.6%), 15 to 19 (81.3%), and 20 or more (64.2%; p < 0.001).
      CONCLUSIONS: In this large-cohort analysis, the IMPACT score accurately predicted
      mortality following pediatric OHT. The IMPACT score could therefore be useful to
      providers for organ allocation and prognostication in this patient population.

PMID- 22385821
TI  - Hypothermia severely effects performance of nitinol-based endovascular grafts in
      vitro.
AB  - BACKGROUND: Nitinol is an alloy that serves as the base for numerous medical
      devices, including the GORE TAG Thoracic Endoprosthesis (W.L. Gore & Associates,
      Flagstaff, AZ) thoracic aortic graft device. Given the increasing use of
      therapeutic hypothermia used during the placement these devices and in post
      cardiac arrest situations, we sought to understand the impact of hypothermia on
      this device. METHODS: Five 34-mm TAG devices were deployed in a temperature
      controlled chamber at 20 degrees C, 25 degrees C, 30 degrees C, 35 degrees , and
      37 degrees C (25 total devices). A halographic measurement device was used to
      measure radial expansive force and normalized to the force at 37 degrees C. Three
      34-mm TAG devices were similarly deployed in a temperature-controlled water bath
      at each of the above temperatures. A laser micrometer was utilized to measure
      deployed diameter. RESULTS: A statistically significant decrease in expansive
      force at 20 degrees C, 25 degrees C, and 30 degrees C of 65%, 46%, and 6%,
      respectively, was noted. A statistically significant decrease in radial diameter
      at 20 degrees C and 25 degrees C of 17% and 11%, respectively, was noted.
      Although a 9% difference was noted at 30 degrees C, it was not significant.
      CONCLUSIONS: The nitinol-based TAG device shows marked decreases in radial
      expansive force and deployed diameter at temperatures at or below 30 degrees C.
      Surgeons should be aware of the potential implications of placing nitinol-based
      endoprostheses in hypothermic conditions. In addition, all health care providers
      should be aware of the changes that occur in nitinol-based endoprostheses during
      therapeutic hypothermia.

PMID- 22385822
TI  - Human lung cancer cells grown on acellular rat lung matrix create perfusable
      tumor nodules.
AB  - BACKGROUND: Extracellular matrix allows lung cancer to form its shape and grow.
      Recent studies on organ reengineering for orthotopic transplantation have
      provided a new avenue for isolating purified native matrix to use for growing
      cells. Whether human lung cancer cells grown in a decellularized rat lung matrix
      would create perfusable human lung cancer nodules was tested. METHODS: Rat lungs
      were harvested and native cells were removed using sodium dodecyl sulfate and
      Triton X-100 in a decellularization chamber to create a decellularized rat lung
      matrix. Human A549, H460, or H1299 lung cancer cells were placed into the
      decellularized rat lung matrix and grown in a customized bioreactor with
      perfusion of oxygenated media for 7 to 14 days. RESULTS: Decellularized rat lung
      matrix showed preservation of matrix architecture devoid of all rat cells. All
      three human lung cancer cell lines grown in the bioreactor developed tumor
      nodules with intact vasculature. Moreover, the lung cancer cells developed a
      pattern of growth similar to the original human lung cancer. CONCLUSIONS:
      Overall, this study shows that human lung cancer cells form perfusable tumor
      nodules in a customized bioreactor on a decellularized rat lung matrix created by
      a customized decellularization chamber. The lung cancer cells grown in the matrix
      had features similar to the original human lung cancer. This ex vivo model can be
      used potentially to gain a deeper understanding of the biologic processes
      involved in human lung cancer.

PMID- 22385823
TI  - A platform for evaluating sperm RNA biomarkers: dysplasia of the fibrous sheath-
      testing the concept.
AB  - OBJECTIVE: To investigate the potential use of correlative microarray-based
      transcript pairs as candidate markers for male fertility using dysplasia of the
      fibrous sheath (DFS) as an affected model. It is widely recognized that
      microarray technology may be limited by cost and that the quality of the
      transcript remains relatively unknown. To address these issues, we analyzed the
      stable transcript pairs by qPCR with a systematic primer design process. DESIGN:
      Experimental study. SETTING: University. PATIENT(S): Men with proven fertility
      and men with a diagnosis of DFS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Primer sequences for six genes of interest were designed using Oligo7 and
      Primer3Plus. Primer specificity was initially assessed in silico by searching the
      ENSEMBL, University of California Santa Cruz, and National Center for
      Biotechnology Information databases for nontarget complementary sequences
      throughout the genome. The ability of transcript pairs to classify samples from
      males of proven fertility away from DFS was assessed. RESULT(S): In conjunction
      with identifying four new stable transcript pairs, comparison of the DFS qPCR
      C(t) correlation coefficients revealed the disruption of four stable fertile
      sample transcript pairs. This suite of transcript pairs resolves DFS.
      CONCLUSION(S): The results show that with effectively designed primers, qPCR may
      provide an affordable molecular assay to assess male fertility status.

PMID- 22385824
TI  - A validation study of the Keyboard Personal Computer Style instrument (K-PeCS)
      for use with children.
AB  - This study examines a potential instrument for measurement of typing postures of
      children. This paper describes inter-rater, test-retest reliability and
      concurrent validity of the Keyboard Personal Computer Style instrument (K-PeCS),
      an observational measurement of postures and movements during keyboarding, for
      use with children. Two trained raters independently rated videos of 24 children
      (aged 7-10 years). Six children returned one week later for identifying test
      retest reliability. Concurrent validity was assessed by comparing ratings
      obtained using the K-PECS to scores from a 3D motion analysis system. Inter-rater
      reliability was moderate to high for 12 out of 16 items (Kappa: 0.46 to 1.00;
      correlation coefficients: 0.77-0.95) and test-retest reliability varied across
      items (Kappa: 0.25 to 0.67; correlation coefficients: r = 0.20 to r = 0.95).
      Concurrent validity compared favourably across arm pathlength, wrist extension
      and ulnar deviation. In light of the limitations of other tools the K-PeCS offers
      a fairly affordable, reliable and valid instrument to address the gap for
      measurement of typing styles of children, despite the shortcomings of some items.
      However further research is required to refine the instrument for use in
      evaluating typing among children.

PMID- 22385825
TI  - Rhinophyma and non-melanoma skin cancer: an update.

PMID- 22385826
TI  - Maternal serum proteome changes between the first and third trimester of
      pregnancy in rural southern Nepal.
AB  - Characterization of normal changes in the serum proteome during pregnancy may
      enhance understanding of maternal physiology and lead to the development of new
      gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two
      dimensional difference in-gel electrophoresis (DIGE) was used to assess changes
      in relative protein abundance between paired serum samples collected in the first
      and third trimesters. One-hundred and forty-five of over 700 protein spots in
      DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in
      abundance across trimesters. Additional filtering using a Bonferroni correction
      reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric
      analysis detected 38 proteins associated with gestational age, cytoskeletal
      remodeling, blood pressure regulation, lipid and nutrient transport, and
      inflammation. One new protein, pregnancy-specific beta-glycoprotein 4 was
      detected. A follow-up isotope tagging for relative and absolute quantitation
      (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of
      which 11 exhibited significant (p < 0.05) differences between trimesters. Four of
      these proteins: gelsolin, complement C1r subcomponent, alpha-1-acid glycoprotein,
      and alpha-1B-glycoprotein also changed in the DIGE analysis. Although not
      previously associated with normal pregnancy, gelsolin decreased in abundance by
      the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in
      abundance of proteins in serum that are associated with syncytiotrophoblasts
      (gelsolin, pregnancy-specific beta-1 glycoprotein 1 and beta-2-glycoprotein I)
      probably reflect dynamics of a placental proteome shed into maternal circulation
      during pregnancy. Measurement of changes in the maternal serum proteome, when
      linked with birth outcomes, may yield biomarkers for tracking reproductive health
      in resource poor settings in future studies.

PMID- 22385827
TI  - Protein recognition of hetero-/homoleptic ruthenium(II) tris(bipyridine)s for
      alpha-chymotrypsin and cytochrome c.
AB  - We examined the relationship between the structures of hetero-/homoleptic
      ruthenium(II) tris(bipyridine) metal complexes (Ru(II)(bpy)(3)) and their binding
      properties for alpha-chymotrypsin (ChT) and cytochrome c (cyt c). Heteroleptic
      compound 1a binds to both ChT and cyt c in 1:1 ratio, whereas homoleptic 2 forms
      1:2 protein complex with ChT but 1:1 complex with cyt c. These results suggest
      that the structure of the recognition cavity in Ru(II)(bpy)(3) can be designed
      for shape complementarity to the targeted proteins. In addition, Ru(II)(bpy)(3)
      complexes were found to be potent inhibitors of cyt c reduction and to permeate
      A549 cells.

PMID- 22385828
TI  - Toward systematic integration between self-determination theory and motivational
      interviewing as examples of top-down and bottom-up intervention development:
      autonomy or volition as a fundamental theoretical principle.
AB  - Clinical interventions can be developed through two distinct pathways. In the
      first, which we call top-down, a well-articulated theory drives the development
      of the intervention, whereas in the case of a bottom-up approach, clinical
      experience, more so than a dedicated theoretical perspective, drives the
      intervention. Using this dialectic, this paper discusses Self-Determination
      Theory (SDT) 12 and Motivational Interviewing (MI) 3 as prototypical examples of
      a top-down and bottom-up approaches, respectively. We sketch the different
      starting points, foci and developmental processes of SDT and MI, but equally note
      the complementary character and the potential for systematic integration between
      both approaches. Nevertheless, for a deeper integration to take place, we contend
      that MI researchers might want to embrace autonomy as a fundamental basic process
      underlying therapeutic change and we discuss the advantages of doing so.

PMID- 22385829
TI  - "Doctor, I have a long, sausage-shaped lump in my abdomen".

PMID- 22385830
TI  - Utility of the estimated glucose disposal rate as a marker of microvascular
      complications in young adults with type 1 diabetes.
AB  - In 61 young adults with type 1 diabetes mellitus, the estimated glucose disposal
      rate (eGDR), a validated marker for insulin resistance, correlated positively
      with the prevalence of microvascular complications. In the absence of an
      established vascular risk calculator specific to diabetes, the eGDR may present a
      useful clinical tool in the assessment of complication risk in type 1 diabetes.

PMID- 22385831
TI  - Exercise training in high-risk ethnic populations with type 2 diabetes: a
      systematic review of clinical trials.
AB  - BACKGROUND: To review clinical trials that have prescribed exercise training in
      high-risk, ethnic populations with type 2 diabetes mellitus (T2DM) and delineate
      areas for future research. METHOD: A systematic review using computerized
      databases was performed. RESULTS: The systematic review located nine trials,
      including four uncontrolled trials, and five randomized controlled trials (RCTs)
      that included 521 participants. Cohorts studied included African, Indian,
      Polynesian, Hispanic, Arabian, and Chinese peoples and interventions included
      aerobic training, resistance training or a combination thereof. Several trials
      documented improvements in HbA1c, insulin action, body composition, blood lipids
      and systolic and diastolic blood pressure. In general, a longer duration and
      greater frequency of training resulted in greater adaptation. Studies
      demonstrating no effect were generally limited by an inadequate intervention.
      There was evidence of differential training responses between Caucasians and non
      Caucasians in two studies drawing such comparisons. CONCLUSIONS: Robust RCTs
      prescribing appropriate, targeted interventions and investigating relevant
      outcomes may be required to stimulate greater advocacy for exercise as a
      therapeutic adjunct for diabetes management in these populations. Investigations
      should be extended to other high-risk populations, particularly indigenous
      peoples who suffer an extreme burden of T2DM. Translation of research into
      clinical application should remain the overall objective.

PMID- 22385832
TI  - The excessive use of inhaled corticosteroids in chronic obstructive pulmonary
      disease.
AB  - Despite the fact that the recommendations of the main clinical guidelines have
      restricted the indications for inhaled corticosteroids in chronic obstructive
      pulmonary disease (COPD), currently more than 80% of patients are receiving this
      treatment in Spain, mostly with high doses. A detailed review of the literature
      does not justify the use of these high doses, a position that agrees with the
      recommendations of the FDA. A re-evaluation of their safety, the consistency of
      the data on their efficacy showing similar results with moderate doses and a
      better patient selection require the use of this treatment in COPD patients to be
      reconsidered.

PMID- 22385834
TI  - MFG-E8 activates proliferation of vascular smooth muscle cells via integrin
      signaling.
AB  - An accumulation of milk fat globule EGF-8 protein (MFG-E8) occurs within the
      context of arterial wall inflammatory remodeling during aging, hypertension,
      diabetes mellitus, or atherosclerosis. MFG-E8 induces VSMC invasion, but whether
      it affects VSMC proliferation, a salient feature of arterial inflammation, is
      unknown. Here, we show that in the rat arterial wall in vivo, PCNA and Ki67,
      markers of cell cycle activation, increase with age between 8 and 30 months. In
      fresh and early passage VSMC isolated from old aortae, an increase in CDK4 and
      PCNA, an increase in the acceleration of cell cycle S and G2 phases, decrease in
      the G1/G0 phase, and an increase in PDGF and its receptors confer elevated
      proliferative capacity, compared to young VSMC. Increased coexpression and
      physical interaction of MFG-E8 and integrin alphavbeta5 occur with aging in both
      the rat aortic wall in vivo and in VSMC in vitro. In young VSMC in vitro, MFG-E8
      added exogenously, or overexpressed endogenously, triggers phosphorylation of
      ERK1/2, augmented levels of PCNA and CDK4, increased BrdU incorporation, and
      promotes proliferation, via alphavbeta5 integrins. MFG-E8 silencing, or its
      receptor inhibition, or the blockade of ERK1/2 phosphorylation in these cells
      reduces PCNA and CDK4 levels and decelerates the cell cycle S phase, conferring a
      reduction in proliferative capacity. Collectively, these results indicate that
      MFG-E8 in a dose-dependent manner coordinates the expression of cell cycle
      molecules and facilitates VSMC proliferation via integrin/ERK1/2 signaling. Thus,
      an increase in MFG-E8 signaling is a mechanism of the age-associated increase in
      aortic VSMC proliferation.

PMID- 22385835
TI  - Neuroendocrine signalling: natural variations on a Ca2+ theme.
AB  - This special issue on Ca(2+) signalling in neuroendocrine cells is an opportunity
      to assess, through a range of first-class review articles, the complex world of
      endocrine signalling, a complexity that is probably best captured by calling it
      "diversity in unity". The unity comes from the fact that all the endocrine cells
      are excitable cells, able to generate action potentials and are using Ca(2+) as
      an essential informational molecule, coupling cell stimulation with the
      activation of secretion, through the exocytotic process. The 'diversity' element,
      illustrated by almost all the reviews, stems from the modalities employed to
      achieve the increase in cytosolic Ca(2+) signal, the balance between the
      participation of Ca(2+) entry through the plasma membrane voltage-operated Ca(2+)
      channels and the release of Ca(2+) from intracellular Ca(2+) stores, and the
      cross-talk between the Ca(2+) and cyclic AMP signalling pathways.

PMID- 22385833
TI  - Maternal antioxidants prevent beta-cell apoptosis and promote formation of dual
      hormone-expressing endocrine cells in male offspring following fetal and neonatal
      nicotine exposure.
AB  - BACKGROUND: Fetal and neonatal nicotine exposure causes beta-cell oxidative
      stress and apoptosis in neonates, leading to adult-onset dysglycemia. The aim of
      the present study was to determine whether an antioxidant intervention could
      prevent nicotine-induced beta-cell loss. METHODS: Nulliparous female Wistar rats
      received daily subcutaneous injections of either saline or nicotine bitartrate
      (1.0 mg/kg per day) for 2 weeks prior to mating until weaning. Nicotine-exposed
      dams received either normal chow or diet containing antioxidants (1000 IU/kg
      vitamin E, 0.25% w/w coenzyme Q10, and 0.1% w/w alpha-lipoic acid) during mating,
      pregnancy, and lactation; saline-exposed dams received normal chow. Pancreatic
      tissue was collected from male offspring at 3 weeks of age to measure beta-cell
      fraction, apoptosis, proliferation, and the presence of cells coexpressing
      insulin and glucagon. RESULTS: The birth weight of offspring born to nicotine
      exposed dams was significantly reduced in those receiving dietary antioxidants
      compared with those fed normal chow. Most interestingly, the antioxidant
      intervention to nicotine-exposed dams prevented the beta-cell loss and apoptosis
      observed in nicotine-exposed male offspring whose mothers did not receive
      antioxidants. Male pups born to nicotine-treated mothers receiving antioxidants
      also had a tendency for increased beta-cell proliferation and a significant
      increase in islets containing insulin/glucagon bihormonal cells compared with the
      other two treatment groups. CONCLUSION: The present study demonstrates that
      exposure to maternal antioxidants protects developing beta-cells from the
      damaging effects of nicotine, thus preserving beta-cell mass.

PMID- 22385836
TI  - Interactions between intracellular free Ca2+ and cyclic AMP in neuroendocrine
      cells.
AB  - Calcium ions and cyclic adenosine monophosphate (cAMP) are virtually ubiquitous
      intracellular signaling molecules in mammalian cells. This paper will focus on
      the cross-talk between Ca(2+) and cAMP mobilizing signaling pathways and
      summarize the underlying molecular mechanisms. Subsequently, workings of
      adenohypophyseal corticotrope cells will be reviewed to highlight the
      physiological relevance of a Ca(2+) cAMP interactions in neuroendocrinology.

PMID- 22385837
TI  - FTIR and SEM analysis of CO2 laser irradiated human enamel.
AB  - OBJECTIVES: Considering the enamel chemical structure, especially carbonate band,
      which has a major role in the caries prevention, the objective of the present
      study was to assess the chemical alterations on the enamel irradiated with CO(2)
      laser by means of FTIR spectroscopy and SEM analysis. DESIGN: The enamel surfaces
      were analysed on a spectrometer for acquisition of the absorption spectrum
      relative to the chemical composition of the control sample. The irradiation was
      conducted with a 10.6-MUm CO(2) laser (0.55W, 660W/cm(2)). The carbonate
      absorption band at 1600-1291cm(-1) as well as the water absorption band at 3793
      2652cm(-1) was measured in each sample after the irradiation. The water band was
      measured again 24-h after the irradiation. The band area of each chemical
      compound was delimited, the background was subtracted, and the area under each
      band was integrated. Each area was normalized by the phosphate band (1190-702cm(
      1)). RESULTS: There was a statistically significant decrease (p<0.05) in the
      water content after irradiation (control: 0.184+/-0.04; irradiated: 0.078+/
      0.026), which increased again after rehydration (0.145+/-0.038). The
      carbonate/phosphate ratio was measured initially (0.112+/-0.029) and its
      reduction after irradiation indicated the carbonate loss (0.088+/-0.014)
      (p<0.05). CONCLUSION: The 10.6-MUm CO(2) laser irradiation diminishes the
      carbonate and water contents in the enamel after irradiation.

PMID- 22385838
TI  - Immunohistochemical analysis of FoxP3+ cells in periapical granulomas and
      radicular cysts.
AB  - OBJECTIVES: To compare the number of FoxP3(+) cells between periapical granulomas
      (PGs) and radicular cysts (RCs), and to correlate this number with the intensity
      of the inflammatory infiltrate in these lesions and with epithelial thickness of
      RCs. STUDY DESIGN: Thirty PGs and 30 RCs were submitted to immunohistochemical
      analysis using an anti-FoxP3 polyclonal antibody. FoxP3(+) cells were counted
      under a light microscope (*400 magnification) in five fields and the mean value
      was calculated for each specimen. Statistical tests were used to evaluate
      differences in the number of FoxP3(+) cells according to type of lesion (PG vs.
      RC), intensity of the inflammatory infiltrate (grade I/II vs. grade III), and
      epithelial thickness of RCs (atrophic vs. hyperplastic). RESULTS: FoxP3(+) cells
      were detected in most PGs (93.3%) and RCs (93.3%). The median number of FoxP3(+)
      cells was 2.40 in PGs and 1.00 in RCs, with this difference being statistically
      significant (P=0.005). No significant differences in the number of FoxP3(+) cells
      were observed in terms of the intensity of the inflammatory infiltrate (P=0.465)
      or epithelial thickness of RCs (P=0.737). CONCLUSIONS: The present results
      suggest a greater participation of regulatory T cells in the modulation of the
      inflammatory response in PGs. In addition, the presence of a less effective
      regulatory environment in RCs, together with the high levels of inflammatory
      mediators as reported in the literature, may contribute to the greater growth
      potential of these lesions.

PMID- 22385839
TI  - Self-determination theory in health care and its relations to motivational
      interviewing: a few comments.
AB  - The papers of this special issue have the dual focus of reviewing research,
      especially clinical trials, testing self-determination theory (SDT) and of
      discussing the relations between SDT and motivational interviewing (MI). Notably,
      trials are reviewed that examined interventions either for behaviors such as
      physical activity and smoking cessation, or for outcomes such as weight loss.
      Although interventions were based on and intended to test the SDT health-behavior
      change model, authors also pointed out that they drew techniques from MI in
      developing the interventions. The current paper refers to these studies and also
      clarifies the meaning of autonomy, which is central to SDT and has been shown to
      be important for effective change. We clarify that the dimension of autonomy
      versus control is conceptually orthogonal to the dimension of independence versus
      dependence, and we emphasize that autonomy or volition, not independence, is the
      important antecedent of effective change. Finally, we point out that SDT and MI
      have had much in common for each has emphasized autonomy. However, a recent MI
      article seems to have changed MI's emphasis from autonomy to change talk as the
      key ingredient for change. We suggest that change talk is likely to be an element
      of effective change only to the degree that the change talk is autonomously
      enacted and that practitioners facilitate change talk in an autonomy supportive
      way.

PMID- 22385840
TI  - The livelihoods of Haitian health-care providers after the january 2010
      earthquake: a pilot study of the economic and quality-of-life impact of emergency
      relief.
AB  - INTRODUCTION: An effective international response to a disaster requires
      cooperation and coordination with the existing infrastructure. In some cases,
      however, international relief efforts can compete with the local work force and
      affect the balance of health-care systems already in place. This study seeks to
      evaluate the impact of the international humanitarian response to the 12 January
      2010 earthquake on Haitian health-care providers (HHP). METHODS: Fifty-nine HHPs
      were surveyed in August of 2010 using a modified World Health Organization
      Quality of Life-Brief questionnaire (WHOQoL-B) that included questions on
      respondents' workload before the earthquake, immediately after, and presently.
      The study population consisted of physicians, nurses, and technicians at public
      hospitals, non-governmental organization (NGO) clinics, and private offices in
      Port-au-Prince, Haiti. RESULTS: Following the earthquake, public hospital and NGO
      providers reported a significant increase in their workload (15 of 17 and 22 of
      26 respondents, respectively). Conversely, 12 of 16 private providers reported a
      significant decrease in workload (p < 0.0001). Although all groups reported
      working a similar number of hours prior to the earthquake (average 40 h/week),
      they reported working significantly different amounts following the earthquake.
      Public hospital and NGO providers averaged more than 50 h/week, and private
      providers averaged just over 33 h/week of employment (p < 0.001).Health-care
      providers working at public hospitals and NGOs, however, had significantly lower
      scores on the WHOQoL-B when answering questions about their environment (p <
      0.001), and in open-ended responses often commented about the lack of potable
      water and poor access to toilets. Providers from all groups expressed
      dissatisfaction with the scope and quality of care provided at public hospitals
      and NGO clinics, as well as disappointment with the reduction in patient volume
      at private practices. CONCLUSIONS: The emergency medical response to the January
      2010 earthquake in Haiti had the unintended consequence of poorly distributing
      work among HHPs. To create a robust health-care system in the long term while
      meeting short-term needs, humanitarian responses should seek to better integrate
      existing systems and involve local providers in the design and implementation of
      an emergency program.

PMID- 22385841
TI  - A synthetic amino acid substitution of Tyr10 in Abeta peptide sequence yields a
      dominant negative variant in amyloidogenesis.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in elderly people,
      and age is the major nongenetic risk factor for sporadic AD. A hallmark of AD is
      the accumulation of amyloid in the brain, which is composed mainly of the amyloid
      beta-peptide (Abeta) in the form of oligomers and fibrils. However, how aging
      induces Abeta aggregation is not yet fully determined. Some residues in the Abeta
      sequence seem to promote Abeta-induced toxicity in association with age-dependent
      risk factors for AD, such as (i) increased GM1 brain membrane content, (ii)
      altered lipid domain in brain membrane, (iii) oxidative stress. However, the role
      of Abeta sequence in promoting aggregation following interaction with the plasma
      membrane is not yet demonstrated. As Tyr10 is implicated in the induction of
      oxidative stress and stabilization of Abeta aggregation, we substituted Tyr 10
      with a synthetic amino acid that abolishes Abeta-induced oxidative stress and
      shows an accelerated interaction with GM1. This variant peptide shows impaired
      aggregation properties and increased affinity for GM1. It has a dominant negative
      effect on amyloidogenesis in vitro, in cellulo, and in isolated synaptosomes. The
      present study shed new light in the understanding of Abeta-membrane interactions
      in Abeta-induced neurotoxicity. It demonstrates the relevance of Abeta sequence
      in (i) Abeta-membrane interaction, underlining the role of age-dependent enhanced
      GM1 content in promoting Abeta aggregation, (ii) Abeta aggregation, and (iii)
      Abeta-induced oxidative stress. Our results open the way for the design of
      peptides aimed to inhibit Abeta aggregation and neurotoxicity.

PMID- 22385842
TI  - Antibody-functionalized fluid-permeable surfaces for rolling cell capture at high
      flow rates.
AB  - Adhesion-based cell capture on surfaces in microfluidic devices forms the basis
      of numerous biomedical diagnostics and in vitro assays. However, the performance
      of these platforms is partly limited by interfacial phenomena that occur at low
      Reynolds numbers. In contrast, cell homing to porous vasculature is highly
      effective in vivo during inflammation, stem cell trafficking, and cancer
      metastasis. Here, we show that a porous, fluid-permeable surface functionalized
      with cell-specific antibodies promotes efficient and selective cell capture in
      vitro. This architecture is advantageous due to enhanced transport as streamlines
      are diverted toward the surface. Moreover, specific cell-surface interactions are
      promoted due to reduced shear, allowing gentle cell rolling and arrest. Together,
      these synergistic effects enable highly effective cell capture at flow rates more
      than an order of magnitude larger than those provided by existing devices with
      solid surfaces.

PMID- 22385843
TI  - The mechanics of FtsZ fibers.
AB  - Inhibition of the Fts family of proteins causes the growth of long filamentous
      cells, indicating that they play some role in cell division. FtsZ polymerizes
      into protofilaments and assembles into the Z-ring at the future site of the
      septum of cell division. We analyze the rigidity of GTP-bound FtsZ protofilaments
      by using cryoelectron microscopy to sample their bending fluctuations. We find
      that the FtsZ-GTP filament rigidity is kappa=4.7+/-1.0*10(-27) Nm(2), with a
      corresponding thermal persistence length of l(p)=1.15+/-0.25MUm, much higher than
      previous estimates. In conjunction with other model studies, our new higher
      estimate for FtsZ rigidity suggests that contraction of the Z-ring may generate
      sufficient force to facilitate cell division. The good agreement between the
      measured mode amplitudes and that predicted by equipartition of energy supports
      our use of a simple mechanical model for FtsZ fibers. The study also provides
      evidence that the fibers have no intrinsic global or local curvatures, such as
      might be caused by partial hydrolysis of the GTP.

PMID- 22385844
TI  - Analysis of molecular movement reveals latticelike obstructions to diffusion in
      heart muscle cells.
AB  - Intracellular diffusion in muscle cells is known to be restricted. Although
      characteristics and localization of these restrictions is yet to be elucidated,
      it has been established that ischemia-reperfusion injury reduces the overall
      diffusion restriction. Here we apply an extended version of raster image
      correlation spectroscopy to determine directional anisotropy and coefficients of
      diffusion in rat cardiomyocytes. Our experimental results indicate that diffusion
      of a smaller molecule (1127 MW fluorescently labeled ATTO633-ATP) is restricted
      more than that of a larger one (10,000 MW Alexa647-dextran), when comparing
      diffusion in cardiomyocytes to that in solution. We attempt to provide a
      resolution to this counterintuitive result by applying a quantitative stochastic
      model of diffusion. Modeling results suggest the presence of periodic
      intracellular barriers situated ~1 MUm apart having very low permeabilities and a
      small effect of molecular crowding in volumes between the barriers. Such
      intracellular structuring could restrict diffusion of molecules of energy
      metabolism, reactive oxygen species, and apoptotic signals, enacting a
      significant role in normally functioning cardiomyocytes as well as in
      pathological conditions of the heart.

PMID- 22385845
TI  - Computational modeling of axonal microtubule bundles under tension.
AB  - Microtubule bundles cross-linked by tau protein serve a variety of neurological
      functions including maintaining mechanical integrity of the axon, promoting
      axonal growth, and facilitating cargo transport. It has been observed that axonal
      damage in traumatic brain injury leads to bundle disorientation, loss of axonal
      viability, and cognitive impairment. This study investigates the initial
      mechanical response of axonal microtubule bundles under uniaxial tension using a
      discrete bead-spring representation. Mechanisms of failure due to traumatic
      stretch loading and their impact on the mechanical response and stability are
      also characterized. This study indicates that cross-linked axonal microtubule
      bundles in tension display stiffening behavior similar to a power-law
      relationship from nonaffine network deformations. Stretching of cross-links and
      microtubule bending were the primary deformation modes at low stresses.
      Microtubule stretch was negligible up to tensile stresses of ~1 MPa. Bundle
      failure occurred by failure of cross-links leading to pull-out of microtubules
      and loss of bundle integrity. This may explain the elongation, undulation, and
      delayed elasticity of axons following traumatic stretch loading. More extensively
      cross-linked bundles withstood higher tensile stresses before failing. The bundle
      mechanical behavior uncovered by these computational techniques should guide
      future experiments on stretch-injured axons.

PMID- 22385846
TI  - Local motion analysis reveals impact of the dynamic cytoskeleton on intracellular
      subdiffusion.
AB  - Intracellular transport is a complex interplay of ballistic transport along
      filaments and of diffusive motion, reliably delivering material and allowing for
      cell differentiation, migration, and proliferation. The diffusive regime,
      including subdiffusive, Brownian, and superdiffusive motion, is of particular
      interest for inferring information about the dynamics of the cytoskeleton
      morphology during intracellular transport. The influence of dynamic cytoskeletal
      states on intracellular transport are investigated in Dictyostelium discoideum
      cells by single particle tracking of fluorescent nanoparticles, to relate
      quantitative motion parameters and intracellular processes before and after
      cytoskeletal disruption. A local mean-square displacement (MSD) analysis
      separates ballistic motion phases, which we exclude here, from diffusive
      nanoparticle motion. In this study, we focus on intracellular subdiffusion and
      elucidate lag-time dependence, with particular focus on the impact of
      cytoskeleton compartments like microtubules and actin filaments. This method
      proves useful for binary motion state distributions. Experimental results are
      compared to simulations of a data-driven Langevin model with finite velocity
      correlations that captures essential statistical features of the local MSD
      algorithm. Specifically, the values of the mean MSD exponent and effective
      diffusion coefficients can be traced back to negative correlations of the
      motion's increments. We clearly identify both microtubules and actin filaments as
      the cause for intracellular subdiffusion and show that actin-microtubule cross
      talk exerts viscosifying effects at timescales larger than 0.2 s. Our findings
      might give insights into material transport and information exchange in living
      cells, which might facilitate gaining control over cell functions.

PMID- 22385847
TI  - Inactivation of Saccharomyces cerevisiae sulfate transporter Sul2p: use it and
      lose it.
AB  - Saccharomyces cerevisiae SO(4)(=) transport is regulated over a wide dynamic
      range. Sulfur starvation causes ~10,000-fold increase in the (35)SO(4)(=) influx
      mediated by transporters Sul1p and Sul2p; >80% of the influx is via Sul2p. Adding
      methionine to S-starved cells causes a 50-fold decline (t(1/2) ~5 min) in SUL1
      and SUL2 mRNA but a slower decline (t(1/2) ~1 h) in transport. In contrast,
      SO(4)(=) addition does not affect mRNA but causes a rapid (t(1/2) = 2-4 min)
      decrease in transport. In met3Delta cells (unable to metabolize SO(4)(=)),
      addition of SO(4)(=) to S-starved cells causes inactivation of (35)SO(4)(=)
      influx over times in which cellular SO(4)(=) contents are nearly constant. The
      relationship between cellular SO(4)(=) and transport inactivation shows that
      cellular SO(4)(=) is not the signal for Sul2p inactivation. Instead, the
      transport inactivation rate has the same dependence on extracellular SO(4)(=) as
      (35)SO(4)(=) influx, indicating that Sul2p exhibits use-dependent inactivation;
      the transport process itself increases the probability of Sul2p inactivation and
      degradation. In addition, there is a transient efflux of SO(4)(=) shortly after
      adding >0.02 mM SO(4)(=) to S-starved met3Delta cells. This transient efflux
      provides further protection against excessive SO(4)(=) influx and may represent
      an alternate transport mode of Sul2p.

PMID- 22385848
TI  - Visualizing the analogy between competitive adsorption and colloid stability to
      restore lung surfactant function.
AB  - We investigated a model of acute respiratory distress syndrome in which the serum
      protein albumin adsorbs to an air-liquid interface and prevents the
      thermodynamically preferable adsorption of the clinical lung surfactant Survanta
      by inducing steric and electrostatic energy barriers analogous to those that
      prevent colloidal aggregation. Chitosan and polyethylene glycol (PEG), two
      polymers that traditionally have been used to aggregate colloids, both allow
      Survanta to quantitatively displace albumin from the interface, but through two
      distinct mechanisms. Direct visualization with confocal microscopy shows that the
      polycation chitosan coadsorbs to interfacial layers of both Survanta and albumin,
      and also colocalizes with the anionic domains of Survanta at the air-liquid
      interface, consistent with it eliminating the electrostatic repulsion by
      neutralizing the surface charges on albumin and Survanta. In contrast, the PEG
      distribution does not change during the displacement of albumin by Survanta,
      consistent with PEG inducing a depletion attraction sufficient to overcome the
      repulsive energy barrier toward adsorption.

PMID- 22385849
TI  - NMR determination of protein partitioning into membrane domains with different
      curvatures and application to the influenza M2 peptide.
AB  - The M2 protein of the influenza A virus acts both as a drug-sensitive proton
      channel and mediates virus budding through membrane scission. The segment
      responsible for causing membrane curvature is an amphipathic helix in the
      cytoplasmic domain of the protein. Here, we use (31)P and (13)C solid-state NMR
      to examine M2-induced membrane curvature. M2(22-46), which includes only the
      transmembrane (TM) helix, and M2(21-61), which contains an additional amphipathic
      helix, are studied. (31)P chemical shift lineshapes indicate that M2(21-61)
      causes a high-curvature isotropic phase to both cholesterol-rich virus-mimetic
      membranes and 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayers, whereas M2(22
      46) has minimal effect. The lamellar and isotropic domains have distinct (31)P
      isotropic chemical shifts, indicating perturbation of the lipid headgroup
      conformation by the amphipathic helix. (31)P- and (13)C-detected (1)H T(2)
      relaxation and two-dimensional peptide-lipid correlation spectra show that M2(21
      61) preferentially binds to the high-curvature domain. (31)P linewidths indicate
      that the isotropic vesicles induced by M2(21-61) are 10-35 nm in diameter, and
      the virus-mimetic vesicles are smaller than the 1,2-dimyristoyl-sn-glycero-3
      phosphocholine vesicles. A strong correlation is found between high membrane
      curvature and weak drug-binding ability of the TM helix. Thus, the M2 amphipathic
      helix causes membrane curvature, which in turn perturbs the TM helix
      conformation, abolishing drug binding. These NMR experiments are applicable to
      other curvature-inducing membrane proteins such as fusion proteins and
      antimicrobial peptides.

PMID- 22385850
TI  - Determination of membrane-insertion free energies by molecular dynamics
      simulations.
AB  - The accurate prediction of membrane-insertion probability for arbitrary protein
      sequences is a critical challenge to identifying membrane proteins and
      determining their folded structures. Although algorithms based on sequence
      statistics have had moderate success, a complete understanding of the energetic
      factors that drive the insertion of membrane proteins is essential to thoroughly
      meeting this challenge. In the last few years, numerous attempts to define a free
      energy scale for amino-acid insertion have been made, yet disagreement between
      most experimental and theoretical scales persists. However, for a recently
      resolved water-to-bilayer scale, it is found that molecular dynamics simulations
      that carefully mimic the conditions of the experiment can reproduce experimental
      free energies, even when using the same force field as previous computational
      studies that were cited as evidence of this disagreement. Therefore, it is
      suggested that experimental and simulation-based scales can both be accurate and
      that discrepancies stem from disparities in the microscopic processes being
      considered rather than methodological errors. Furthermore, these disparities make
      the development of a single universally applicable membrane-insertion free energy
      scale difficult.

PMID- 22385851
TI  - Single-molecule analysis of the microtubule cross-linking protein MAP65-1 reveals
      a molecular mechanism for contact-angle-dependent microtubule bundling.
AB  - Bundling of microtubules (MTs) is critical for the formation of complex MT
      arrays. In land plants, the interphase cortical MTs form bundles specifically
      following shallow-angle encounters between them. To investigate how cells select
      particular MT contact angles for bundling, we used an in vitro reconstitution
      approach consisting of dynamic MTs and the MT-cross-linking protein MAP65-1. We
      found that MAP65-1 binds to MTs as monomers and inherently targets antiparallel
      MTs for bundling. Dwell-time analysis showed that the affinity of MAP65-1 for
      antiparallel overlapping MTs is about three times higher than its affinity for
      single MTs and parallel overlapping MTs. We also found that purified MAP65-1
      exclusively selects shallow-angle MT encounters for bundling, indicating that
      this activity is an intrinsic property of MAP65-1. Reconstitution experiments
      with mutant MAP65-1 proteins with different numbers of spectrin repeats within
      the N-terminal rod domain showed that the length of the rod domain is a major
      determinant of the range of MT bundling angles. The length of the rod domain also
      determined the distance between MTs within a bundle. Together, our data show that
      the rod domain of MAP65-1 acts both as a spacer and as a structural element that
      specifies the MT encounter angles that are conducive for bundling.

PMID- 22385852
TI  - Minimalist model for force-dependent DNA replication.
AB  - In experiments using optical or magnetic tweezers, investigators have monitored
      the rate at which polymerase enzymes catalyze DNA replication when the template
      strand is subjected to a stretching force. For T7, Klenow, and Sequenase
      polymerases, the replication rate increases modestly at low tension and then
      decreases markedly at higher tension. Molecular-dynamics (MD) simulations using x
      ray structure data for the open and closed complexes of the Taq enzyme with DNA
      revealed that the dependence of replication rate on tension could be accounted
      for in terms of the induced enthalpy changes for the two DNA segments adjacent to
      the site of the added nucleotide. Here, we present a simple, minimalist two
      segment local model (M2L) derived from some striking features seen in the MD
      simulations. The model predicts the tension dependence of the replication rate
      using only structural data and a critical tension, f(*), without recourse to MD
      simulations. At f(*), the outermost DNA segment undergoes a large angular
      reorientation in the open conformation of the enzyme. We give a generic plot for
      the M2L model, apply it to family A and B polymerases and HIV reverse
      transcriptase, and discuss factors that may govern the f(*) flip parameter.

PMID- 22385853
TI  - RNA and its ionic cloud: solution scattering experiments and atomically detailed
      simulations.
AB  - RNA molecules play critical roles in many cellular processes. Traditionally
      viewed as genetic messengers, RNA molecules were recently discovered to have
      diverse functions related to gene regulation and expression. RNA also has great
      potential as a therapeutic and a tool for further investigation of gene
      regulation. Metal ions are an integral part of RNA structure and should be
      considered in any experimental or theoretical study of RNA. Here, we report a
      multidisciplinary approach that combines anomalous small-angle x-ray scattering
      and molecular-dynamics (MD) simulations with explicit solvent and ions around
      RNA. From experiment and simulation results, we find excellent agreement in the
      number and distribution of excess monovalent and divalent ions around a short RNA
      duplex. Although similar agreement can be obtained from a continuum description
      of the solvent and mobile ions (by solving the Poisson-Boltzmann equation and
      accounting for finite ion size), the use of MD is easily extended to flexible RNA
      systems with thermal fluctuations. Therefore, we also model a short RNA
      pseudoknot and find good agreement between the MD results and the experimentally
      derived solution structures. Surprisingly, both deviate from crystal structure
      predictions. These favorable comparisons of experiment and simulations encourage
      work on RNA in all-atom dynamic models.

PMID- 22385854
TI  - The ionic atmosphere around A-RNA: Poisson-Boltzmann and molecular dynamics
      simulations.
AB  - The distributions of different cations around A-RNA are computed by Poisson
      Boltzmann (PB) equation and replica exchange molecular dynamics (MD). Both the
      nonlinear PB and size-modified PB theories are considered. The number of ions
      bound to A-RNA, which can be measured experimentally, is well reproduced in all
      methods. On the other hand, the radial ion distribution profiles show differences
      between MD and PB. We showed that PB results are sensitive to ion size and
      functional form of the solvent dielectric region but not the solvent dielectric
      boundary definition. Size-modified PB agrees with replica exchange molecular
      dynamics much better than nonlinear PB when the ion sizes are chosen from
      atomistic simulations. The distribution of ions 14 A away from the RNA central
      axis are reasonably well reproduced by size-modified PB for all ion types with a
      uniform solvent dielectric model and a sharp dielectric boundary between solvent
      and RNA. However, this model does not agree with MD for shorter distances from
      the A-RNA. A distance-dependent solvent dielectric function proposed by another
      research group improves the agreement for sodium and strontium ions, even for
      shorter distances from the A-RNA. However, Mg(2+) distributions are still at
      significant variances for shorter distances.

PMID- 22385855
TI  - Using DNA as a fiducial marker to study SMC complex interactions with the atomic
      force microscope.
AB  - Atomic force microscopy can potentially provide information on protein volumes,
      shapes, and interactions but is susceptible to variable tip-induced artifacts. In
      this study, we present an atomic force microscopy approach that can measure
      volumes of nonglobular polypeptides such as structural maintenance of chromosomes
      (SMC) proteins, and use it to study the interactions that occur within and
      between SMC complexes. Together with the protein of interest, we coadsorb a DNA
      molecule and use it as a fiducial marker to account for tip-induced artifacts
      that affect both protein and DNA, allowing normalization of protein volumes from
      images taken on different days and with different tips. This approach
      significantly reduced the error associated with volume analysis, and allowed
      determination of the oligomeric states and architecture of the Bacillus subtilis
      SMC complex, formed by the SMC protein, and by the smaller ScpA and ScpB
      subunits. This work reveals that SMC and ScpB are dimers and that ScpA is a
      stable monomer. Moreover, whereas ScpA binds directly to SMC, ScpB only binds to
      SMC in the presence of ScpA. Notably, the presence of both ScpA and ScpB favored
      the formation of higher-order structures of SMC complexes, suggesting a role for
      these subunits in the organization of SMC oligomers.

PMID- 22385856
TI  - Unwrapping of nucleosomal DNA ends: a multiscale molecular dynamics study.
AB  - To permit access to DNA-binding proteins involved in the control and expression
      of the genome, the nucleosome undergoes structural remodeling including
      unwrapping of nucleosomal DNA segments from the nucleosome core. Here we examine
      the mechanism of DNA dissociation from the nucleosome using microsecond timescale
      coarse-grained molecular dynamics simulations. The simulations exhibit short
      lived, reversible DNA detachments from the nucleosome and long-lived DNA
      detachments not reversible on the timescale of the simulation. During the short
      lived DNA detachments, 9 bp dissociate at one extremity of the nucleosome core
      and the H3 tail occupies the space freed by the detached DNA. The long-lived DNA
      detachments are characterized by structural rearrangements of the H3 tail
      including the formation of a turn-like structure at the base of the tail that
      sterically impedes the rewrapping of DNA on the nucleosome surface. Removal of
      the H3 tails causes the long-lived detachments to disappear. The physical
      consistency of the CG long-lived open state was verified by mapping a CG
      structure representative of this state back to atomic resolution and performing
      molecular dynamics as well as by comparing conformation-dependent free energies.
      Our results suggest that the H3 tail may stabilize the nucleosome in the open
      state during the initial stages of the nucleosome remodeling process.

PMID- 22385857
TI  - Protein folding is mechanistically robust.
AB  - Markov state models (MSMs) have proven to be useful tools in simulating large and
      slowly-relaxing biological systems like proteins. MSMs model proteins through
      dynamics on a discrete-state energy landscape, allowing molecules to effectively
      sample large regions of phase space. In this work, we use aspects of MSMs to ask:
      is protein folding mechanistically robust? We first provide a definition of
      mechanism in the context of Markovian models, and we later use perturbation
      theory and the concept of parametric sloppiness to show that parts of the MSM
      eigenspectrum are resistant to perturbation. We introduce a new, to our
      knowledge, Bayesian metric by which eigenspectrum robustness can be evaluated,
      and we discuss the implications of mechanistic robustness and possible new
      applications of MSMs to understanding biophysical phenomena.

PMID- 22385858
TI  - Biological channeling of a reactive intermediate in the bifunctional enzyme
      DmpFG.
AB  - It has been hypothesized that the bifunctional enzyme DmpFG channels its
      intermediate, acetaldehyde, from one active site to the next using a buried
      intermolecular channel identified in the crystal structure. This channel appears
      to switch between an open and a closed conformation depending on whether the
      coenzyme NAD(+) is present or absent. Here, we applied molecular dynamics and
      metadynamics to investigate channeling within DmpFG in both the presence and
      absence of NAD(+). We found that substrate channeling within this enzyme is
      energetically feasible in the presence of NAD(+) but was less likely in its
      absence. Tyr-291, a proposed control point at the channel's entry, does not
      appear to function as a molecular gate. Instead, it is thought to orientate the
      substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may
      function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at
      the channel's exit appear to have an important role in controlling the entry of
      acetaldehyde into the DmpF active site.

PMID- 22385859
TI  - Exploring the energy landscapes of protein folding simulations with Bayesian
      computation.
AB  - Nested sampling is a Bayesian sampling technique developed to explore probability
      distributions localized in an exponentially small area of the parameter space.
      The algorithm provides both posterior samples and an estimate of the evidence
      (marginal likelihood) of the model. The nested sampling algorithm also provides
      an efficient way to calculate free energies and the expectation value of
      thermodynamic observables at any temperature, through a simple post processing of
      the output. Previous applications of the algorithm have yielded large efficiency
      gains over other sampling techniques, including parallel tempering. In this
      article, we describe a parallel implementation of the nested sampling algorithm
      and its application to the problem of protein folding in a Go-like force field of
      empirical potentials that were designed to stabilize secondary structure elements
      in room-temperature simulations. We demonstrate the method by conducting folding
      simulations on a number of small proteins that are commonly used for testing
      protein-folding procedures. A topological analysis of the posterior samples is
      performed to produce energy landscape charts, which give a high-level description
      of the potential energy surface for the protein folding simulations. These charts
      provide qualitative insights into both the folding process and the nature of the
      model and force field used.

PMID- 22385860
TI  - An atomistic view on human hemoglobin carbon monoxide migration processes.
AB  - A significant amount of work has been devoted to obtaining a detailed atomistic
      knowledge of the human hemoglobin mechanism. Despite this impressive research, to
      date, the ligand diffusion processes remain unclear and controversial. Using
      recently developed computational techniques, PELE, we are capable of addressing
      the ligand migration processes. First, the methodology was tested on myoglobin's
      CO migration, and the results were compared with the wealth of theoretical and
      experimental studies. Then, we explored both hemoglobin tense and relaxed states
      and identified the differences between the alpha-and beta-subunits. Our results
      indicate that the proximal site, equivalent to the Xe1 cavity in myoglobin, is
      never visited. Furthermore, strategically positioned residues alter the diffusion
      processes within hemoglobin's subunits and suggest that multiple pathways exist,
      especially diversified in the alpha-globins. A significant dependency of the
      ligand dynamics on the tertiary structure is also observed.

PMID- 22385861
TI  - A desolvation model for trifluoroethanol-induced aggregation of enhanced green
      fluorescent protein.
AB  - Studies of amyloid disease-associated proteins in aqueous solutions containing
      2,2,2-trifluoroethanol (TFE) have shown that the formation of structural
      intermediates is often correlated with enhanced protein aggregation. Here,
      enhanced green fluorescent protein (EGFP) is used as a model protein system to
      investigate the causal relationship between TFE-induced structural transitions
      and aggregation. Using circular dichroism spectroscopy, light scattering
      measurements, and transmission electron microscopy imaging, we demonstrate that
      population of a partially alpha-helical, monomeric intermediate is roughly
      correlated with the growth of beta-sheet-rich, flexible fibrils for acid
      denatured EGFP. By fitting our circular dichroism data to a model in which TFE
      water mixtures are assumed to be ideal solutions, we show that increasing
      entropic costs of protein solvation in TFE-water mixtures may both cause the
      population of the intermediate state and increase aggregate production. Tertiary
      structure and electrostatic repulsion also impede aggregation. We conclude that
      initiation of EGFP aggregation in TFE likely involves overcoming of multiple
      protective factors, rather than stabilization of aggregation-prone structural
      elements.

PMID- 22385862
TI  - Effects of Hofmeister ions on the alpha-helical structure of proteins.
AB  - The molecular conformation of proteins is sensitive to the nature of the aqueous
      environment. In particular, the presence of ions can stabilize or destabilize
      (denature) protein secondary structure. The underlying mechanisms of these
      actions are still not fully understood. Here, we combine circular dichroism (CD),
      single-molecule Forster resonance energy transfer, and atomistic computer
      simulations to elucidate salt-specific effects on the structure of three peptides
      with large alpha-helical propensity. CD indicates a complex ion-specific
      destabilization of the alpha-helix that can be rationalized by using a single
      salt-free computer simulation in combination with the recently introduced scheme
      of ion-partitioning between nonpolar and polar peptide surfaces. Simulations
      including salt provide a molecular underpinning of this partitioning concept.
      Furthermore, our single-molecule Forster resonance energy transfer measurements
      reveal highly compressed peptide conformations in molar concentrations of
      NaClO(4) in contrast to strong swelling in the presence of GdmCl. The compacted
      states observed in the presence of NaClO(4) originate from a tight ion-backbone
      network that leads to a highly heterogeneous secondary structure distribution and
      an overall lower alpha-helical content that would be estimated from CD. Thus,
      NaClO(4) denatures by inducing a molten globule-like structure that seems
      completely off-pathway between a fully folded helix and a coil state.

PMID- 22385863
TI  - A delicate interplay of structure, dynamics, and thermodynamics for function: a
      high pressure NMR study of outer surface protein A.
AB  - Outer surface protein A (OspA) is a crucial protein in the infection of Borrelia
      burgdorferi causing Lyme disease. We studied conformational fluctuations of OspA
      with high-pressure (15)N/(1)H two-dimensional NMR along with high-pressure
      fluorescence spectroscopy. We found evidence within folded, native OspA for rapid
      local fluctuations of the polypeptide backbone in the nonglobular single layer
      beta-sheet connecting the N- and C-terminal domains with tau << ms, which may
      give the two domains certain independence in mobility and thermodynamic
      stability. Furthermore, we found that folded, native OspA is in equilibrium (tau
      >> ms) with a minor conformer I, which is almost fully disordered and hydrated
      for the entire C-terminal part of the polypeptide chain from beta8 to the C
      terminus. Conformer I is characterized with DeltaG(0) = 32 +/- 9 kJ/mol and
      DeltaV(0) = -140 +/- 40 mL/mol, populating only ~0.001% at 40 degrees C at 0.1
      MPa, pH 5.9. Because in the folded conformer the receptor binding epitope of OspA
      is buried in the C-terminal domain, its transition into conformer I under in vivo
      conditions may be critical for the infection of B. burgdorferi. The formation and
      stability of the peculiar conformer I are apparently supported by a large packing
      defect or cavity located in the C-terminal domain.

PMID- 22385864
TI  - Multi-wavelength anomalous diffraction using medium-angle X-ray solution
      scattering (MADMAX).
AB  - Proteins are dynamic molecules whose function in virtually all biological
      processes requires conformational motion. Direct experimental probes of protein
      structure in solution are needed to characterize these motions. Anomalous
      scattering from proteins in solution has the potential to act as a precise
      molecular ruler to determine the positions of specific chemical groups or atoms
      within proteins under conditions in which structural changes can take place free
      from the constraints of crystal contacts. In solution, anomalous diffraction has
      two components: a set of cross-terms that depend on the relative location of the
      anomalous centers and the rest of the protein, and a set of pure anomalous terms
      that depend on the distances between the anomalous centers. The cross-terms are
      demonstrated here to be observable and to provide direct information about the
      distance between the anomalous center and the center of mass of the protein. The
      second set of terms appears immeasurably small in the context of current
      experimental capabilities. Here, we outline the theory underlying anomalous
      scattering from proteins in solution, predict the anomalous differences expected
      on the basis of atomic coordinate sets, and demonstrate the measurement of
      anomalous differences at the iron edge for solutions of myoglobin and hemoglobin.

PMID- 22385865
TI  - Excitation spectra and brightness optimization of two-photon excited probes.
AB  - Two-photon probe excitation data are commonly presented as absorption cross
      section or molecular brightness (the detected fluorescence rate per molecule). We
      report two-photon molecular brightness spectra for a diverse set of organic and
      genetically encoded probes with an automated spectroscopic system based on
      fluorescence correlation spectroscopy. The two-photon action cross section can be
      extracted from molecular brightness measurements at low excitation intensities,
      while peak molecular brightness (the maximum molecular brightness with increasing
      excitation intensity) is measured at higher intensities at which probe
      photophysical effects become significant. The spectral shape of these two
      parameters was similar across all dye families tested. Peak molecular brightness
      spectra, which can be obtained rapidly and with reduced experimental complexity,
      can thus serve as a first-order approximation to cross-section spectra in
      determining optimal wavelengths for two-photon excitation, while providing
      additional information pertaining to probe photostability. The data shown should
      assist in probe choice and experimental design for multiphoton microscopy
      studies. Further, we show that, by the addition of a passive pulse splitter,
      nonlinear bleaching can be reduced--resulting in an enhancement of the
      fluorescence signal in fluorescence correlation spectroscopy by a factor of two.
      This increase in fluorescence signal, together with the observed resemblance of
      action cross section and peak brightness spectra, suggests higher-order
      photobleaching pathways for two-photon excitation.

PMID- 22385866
TI  - How slow is the transbilayer diffusion (flip-flop) of cholesterol?

PMID- 22385868
TI  - Imaging protein structure in water at 2.7 nm resolution by transmission electron
      microscopy.
AB  - We demonstrate an in situ transmission electron microscopy technique for imaging
      proteins in liquid water at room temperature. Liquid samples are loaded into a
      microfabricated environmental cell that isolates the sample from the vacuum with
      thin silicon nitride windows. We show that electron micrographs of acrosomal
      bundles in water are similar to bundles imaged in ice, and we determined the
      resolution to be at least 2.7 nm at doses of ~35 e/A(2). The resolution was
      limited by the thickness of the window and radiation damage. Surprisingly, we
      observed a smaller fall-off in the intensity of reflections in room-temperature
      water than in 98 K ice. Thus, our technique extends imaging of unstained and
      unlabeled macromolecular assemblies in water from the resolution of the light
      microscope to the nanometer resolution of the electron microscope. Our results
      suggest that real-time imaging of protein dynamics is conceptually feasible.

PMID- 22385869
TI  - Exploitation of a turbot (Scophthalmus maximus L.) immune-related expressed
      sequence tag (EST) database for microsatellite screening and validation.
AB  - In this study, we identified and characterized 160 microsatellite loci from an
      expressed sequence tag (EST) database generated from immune-related organs of
      turbot (Scophthalmus maximus). A final set of 83 new polymorphic microsatellites
      were validated after the analysis of 40 individuals of Atlantic origin including
      both wild and farmed individuals. The allele number and the expected
      heterozygosity ranged from 2 to 18 and from 0.021 to 0.951, respectively.
      Evidences of null alleles at moderate-high frequencies were detected at six loci
      using population data. None of the analysed loci showed deviations from Mendelian
      segregation after the analysis of five full-sib families including approximately
      92 individuals/family. The markers are used to consolidate the turbot genetic
      map, and because they are mostly EST-derived, they will be very useful for
      comparative genomic studies within flatfishes and with model fish species. Using
      an in silico approach, we detected significant homologies of microsatellite
      sequences with the EST databases of the flatfish species with highest genomic
      resources (Senegalese sole, Atlantic halibut, bastard halibut) in 31% of these
      turbot markers. The conservation of these microsatellites within
      Pleuronectiformes will pave the way for anchoring genetic maps of different
      species and identifying genomic regions related to productive traits.

PMID- 22385870
TI  - The need for improved neutropenia risk assessment in DLBCL patients receiving R
      CHOP-21: findings from clinical practice.
AB  - Febrile neutropenia (FN) risk-assessment and granulocyte-colony stimulating
      factor (G-CSF) prophylaxis use in clinical practice was evaluated in patients
      with diffuse large B-cell lymphoma receiving R-CHOP-21. More G-CSF primary
      prophylaxis was used in patients assessed as high FN risk, but R-CHOP-21 was
      associated with substantial myelotoxicity in both high- and low-risk groups. In a
      multivariate analysis, older age, poor performance status, lower baseline
      hemoglobin, and lack of G-CSF prophylaxis were significantly associated with
      occurrence of FN in any cycle. Results highlight the need for improved FN risk
      assessment and thorough guideline adherence to further reduce FN and better
      support chemotherapy delivery.

PMID- 22385871
TI  - Concurrent splenic diffuse red pulp small B-cell lymphoma and benign clonal
      proliferation of T-cell large granular lymphocytes.

PMID- 22385872
TI  - Meeting in the middle: motivational interviewing and self-determination theory.

PMID- 22385873
TI  - Gait differs between unilateral and bilateral knee osteoarthritis.
AB  - OBJECTIVES: To compare walking biomechanics in the most painful leg, and symmetry
      in biomechanics between legs, in individuals with (1) unilateral pain and
      structural osteoarthritis (OA), (2) unilateral pain, but bilateral structural OA,
      and (3) bilateral pain and structural OA and in (4) an asymptomatic control
      group. DESIGN: Cohort study. SETTING: Laboratory based. PARTICIPANTS:
      Participants with symptomatic and/or radiographic medial tibiofemoral OA in one
      or both knees (n=91), and asymptomatic control participants (n=31).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The peak knee adduction
      moment, peak knee flexion moment, knee varus-valgus angle, peak knee flexion
      angle, toe-out, and trunk lean were computed from 3-dimensional analysis of
      walking at a self-selected speed. RESULTS: After controlling for walking speed,
      greater trunk lean toward the more painful knee and reduced flexion in the more
      painful knee were observed in all OA groups compared with the control group.
      Between-knee asymmetries indicating greater varus angle and a lower external
      flexion moment in the painful knee were present in those with unilateral pain and
      either unilateral or bilateral structural OA. Knee biomechanics were symmetrical
      in those with bilateral pain and structural OA and in the pain free control
      group. CONCLUSIONS: The presence of pain unilaterally appears to be associated
      with asymmetries in knee biomechanics. Contrary to this, bilateral pain is
      associated with symmetry. This suggests that the symptomatic status of both knees
      should be considered when contemplating unilateral or bilateral biomechanical
      interventions for medial knee OA.

PMID- 22385874
TI  - The physiological significance and potential clinical applications of ghrelin.
AB  - Ghrelin, a natural ligand for the growth hormone (GH)-secretagogue receptor (GHS
      R), is now known to play a role in a number of different physiological processes.
      For example, ghrelin increases GH secretion, feeding, and body weight when
      administered centrally or peripherally. These unique effects of ghrelin should be
      invaluable for the development of novel treatments and disease diagnostic
      techniques. Clinical trials have already been performed to assess the utility of
      ghrelin for the treatment of several disorders including anorexia, cachexia, and
      GH-related disorders. This review summarizes the recent advances in this area of
      research.

PMID- 22385875
TI  - Chloride: the queen of electrolytes?
AB  - BACKGROUND: Channelopathies, defined as diseases that are caused by mutations in
      genes encoding ion channels, are associated with a wide variety of symptoms and
      have been documented extensively over the past decade. In contrast, despite the
      important role of chloride in serum, textbooks in general do not allocate
      chapters exclusively on hypochloremia or hyperchloremia and information on
      chloride other than channelopathies is scattered in the literature. STUDY DESIGN:
      To systematically review the function of chloride in man, data for this review
      include searches of MEDLINE, PubMed, and references from relevant articles
      including the search terms "chloride," "HCl," "chloride channel" "acid-base,"
      "acidosis," "alkalosis," "anion gap" "strong anion gap" "Stewart," "base excess"
      and "lactate." In addition, internal medicine, critical care, nephrology and
      gastroenterology textbooks were evaluated on topics pertaining the assessment and
      management of acid-base disorders, including reference lists from journals or
      textbooks. CONCLUSION: Chloride is, after sodium, the most abundant electrolyte
      in serum, with a key role in the regulation of body fluids, electrolyte balance,
      the preservation of electrical neutrality, acid-base status and it is an
      essential component for the assessment of many pathological conditions. When
      assessing serum electrolytes, abnormal chloride levels alone usually signify a
      more serious underlying metabolic disorder, such as metabolic acidosis or
      alkalosis. Chloride is an important component of diagnostic tests in a wide array
      of clinical situations. In these cases, chloride can be tested in sweat, serum,
      urine and feces. Abnormalities in chloride channel expression and function in
      many organs can cause a range of disorders.

PMID- 22385876
TI  - Lupus: novel therapies in clinical development.
AB  - There have been significant advancements in understanding the immunopathogenesis
      of systemic lupus erythematosus. However, the developments in therapeutics have
      been rather slow. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been
      approved for the treatment of this disease after more than 50 years. Numerous
      biological agents are being developed which target the B cells, T cells, and
      various cytokines. Among anti-B cell therapy, drugs target CD20+ cells
      (ocrelizumab, SBI-087), CD22+ cells (epratuzumab) ?or the receptors of tumor
      necrosis factor (TNF) superfamily (atacicept, LY2127399, A-623). Monoclonal
      antibodies targeting interferon alpha (IFN-alpha) and gamma (IFN-gamma) and
      interleukins (IL-6, 10) are being investigated for SLE. Novel targets include
      toll like receptors, phosphodiesterases, CD40 ligand and retinoid receptors. This
      review discusses various drugs which are in different phases of clinical trials
      and hold promise for patients suffering from this chronic debilitating disease.

PMID- 22385877
TI  - Sleep disorders in morbid obesity.
AB  - The increasing prevalence of obesity has lead to an increase in the prevalence of
      sleep disordered breathing in the general population. The disproportionate
      structural characteristics of the pharyngeal airway and the diminished neural
      regulation of the pharyngeal dilating muscles during sleep predispose the obese
      patients to pharyngeal airway collapsibility. A subgroup of obese apneic patients
      is unable to compensate for the added load of obesity on the respiratory system,
      with resultant daytime hypercapnia. Weight loss using dietary modification and
      life style changes is the safest approach to reducing the severity of sleep
      apnea, but its efficacy is limited on the long run. Although it has inherent
      risks, bariatric surgery provides the most immediate result in alleviating sleep
      apnea. Obesity has been linked also to narcolepsy. The loss of neuropeptides co
      localized in hypocretin neurons is suggested as the potential mechanism. Poor
      sleep quality, which leads to overall sleep loss and excessive daytime sleepiness
      has also become a frequent complaint in this population. Identifying abnormal
      nocturnal eating is critically important for patient care. Both sleep related
      eating disorder and night eating syndrome are treatable and represent potentially
      reversible forms of obesity.

PMID- 22385878
TI  - Optimal drug therapy after aspirin-induced upper gastrointestinal bleeding.
AB  - Upper gastrointestinal bleeding is a common adverse effect of chronic aspirin
      treatment. Traditionally, most physicians might tend to discontinue aspirin
      therapy after related gastrointestinal bleeding. However, recent studies have
      shown that continuation of aspirin is beneficial because of a decrease of
      cardiovascular complications and only a relatively small increase of recurrent
      peptic ulcer bleeding when combined with a proton pump inhibitor. There might be
      individual cases where the burden of recurrent gastrointestinal complications
      outweighs the risk of vascular events. In these cases the physician needs to
      carefully consider other precipitating factors for the recurrent gastrointestinal
      symptoms. At the moment, alternative antiplatelet therapy does not lead to lower
      gastrointestinal risks. In the near future, therapies with a more favorable
      profile might emerge.

PMID- 22385879
TI  - Venous thromboembolism prophylaxis of acutely ill hospitalized medical patients.
      Are we over-treating our patients?
AB  - Venous thromboembolism (VTE) is prevalent and is associated with dire
      consequences. Many VTE events are related to medical hospitalization, and some of
      these events are avoidable when appropriate measures are taken. Despite the
      current knowledge of the prevalence and burden of this disease, many internists
      are reluctant to prescribe pharmacological prophylaxis to "at-risk" medical
      inpatients. The purpose of this review is to analyze the reasons for deferring
      such treatment, in view of the facts as presented in the medical literature. We
      believe that while the literature supports further emphasis on education and
      support systems, Internists are deficient of validated tools to decide upon their
      patient's true risk of clinically overt disease.

PMID- 22385880
TI  - Venous thromboembolism prophylaxis of acutely ill hospitalized medical patients.
      Are we under-treating our patients?
AB  - Venous thromboembolism (VTE) is frequent in patients hospitalized in Internal
      Medicine wards. It carries a considerable morbidity and mortality.
      Recommendations for use of anticoagulation are graded 1A in leading evidence
      based consensus guidelines. Implementation of these guidelines is suboptimal.
      Lack of awareness seems to be an important factor for the low implementation rate
      of thromboprophylaxis in Internal Medicine wards, but other factors may be
      equally important: some clinicians find the data favoring thromboprophylaxis
      unconvincing or believe that pharmacological prevention is too risky for the
      average medical inpatient. The following review will show that although there is
      a dispute about the clinical importance of some manifestations of thromboembolic
      disease, anticoagulation significantly reduces the risk for clinically relevant
      VTE. The bleeding risk in most patients is low and does not outweigh the benefit
      of treatment. Pharmacological or mechanical thromboprophylaxis is cost-effective
      when administered to at-risk patients. Better awareness and judicious use of risk
      assessment models should help the attending physician to balance the risk of VTE
      against the potential bleeding risk.

PMID- 22385881
TI  - Prognostic value of low and high ankle-brachial index in hospitalized medical
      patients.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is frequently underdiagnosed in the
      clinical practice, leading to a lack of opportunity to detect subjects at a high
      risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI)
      represents a noninvasive, objective tool to diagnose PAD and to predict adverse
      outcome. METHODS: ABI was determined by means of Doppler velocimetry, in 707
      patients, aged 50 years or older, consecutively hospitalized in an internal
      medicine ward, who were followed-up for at least 12 months in order to assess all
      cause and CV mortality. RESULTS: Symptomatic PAD affected 8% of the population
      while the prevalence of PAD, defined as ABI <0.90, was 29%; high ABI (>1.40) was
      found in 8% of the patients. After a mean follow-up period of 1.6 years, both low
      and high ABI were independently associated with CV mortality with a hazard ratio
      of 1.99 (p=0.016) for low and 2.13 (p=0.04) for high ABI, compared with normal
      ABI (0.90-1.40). High ABI also independently predicted all-cause mortality with a
      hazard ratio of 1.77 (p=0.04). DISCUSSION: ABI measurement reveals a large number
      of individuals with asymptomatic PAD among those hospitalized in an internal
      medicine department. An increased mortality was observed in patients with both
      low and high ABI. Hospital admission for any reason may serve as an opportunity
      to detect PAD and start appropriate preventive actions.

PMID- 22385882
TI  - KCNJ11 gene E23K variant and therapeutic response to sulfonylureas.
AB  - AIMS: Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive
      potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for
      sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in
      genetic association studies. The aim of the present pharmacogenetic study was to
      examine the effect of sulfonylurea treatment on glycemic control in relationship
      to KCNJ11 E23K variant. PATIENTS AND METHODS: One hundred and one patients with
      type 2 diabetes who failed to achieve HbA1c<7% on previous metformin monotherapy
      were included to the study. Sulfonylurea drug was given in addition to metformin.
      The main outcome of the study was reduction in HbA1c level (DeltaHbA1c) after 6
      month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR
      with melting curve analysis. RESULTS: After 6-month treatment, KCNJ11 K-allele
      carriers had higher decrease in HbA1c compared with EE homozygotes in the
      dominant genetic model (1.04+/-0.10 vs. 0.79+/-0.12%, p=0.036). In the log
      additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01-0.32,
      p=0.038) per each K-allele was observed. The relationship of treatment response
      with KCNJ11 genotype was also significant in the biggest subgroup of patients
      treated with gliclazide (n=55). CONCLUSIONS: Carriers of the KCNJ11 K-allele have
      better therapeutic response to gliclazide. This observation might help to
      identify patients who will have the highest benefit from sulfonylurea treatment.

PMID- 22385883
TI  - Seasonal variations of systemic lupus erythematosus flares in southern France.
AB  - OBJECTIVE: Exposure to sunlight is one of the environmental factors involved in
      the pathogenesis of systemic lupus erythematosus. We investigated whether there
      is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus
      flares in southern France. METHODS: We retrospectively reviewed clinical and
      biological data from all SLE patients hospitalized for a flare of the disease
      during a two year period in our centre and collected corresponding meteorological
      data from the official website of MeteoFrance. RESULTS: Forty one patients, mean
      age 36.7 +/- 13.8 years, were included. Twenty-six patients (63.4%) had kidney
      biopsy performed, showing in all cases proliferative nephritis, associated with
      membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall
      lupus flares with 39% of flares occurred in Spring. Among patients without any
      cutaneous involvement, this seasonal pattern was still observed (p=0.024).
      Patients under antimalarials presented flares significantly later in the sunny
      season than those without (respectively median in July versus May, p=0.044).
      There were strong positive correlations between occurrence of lupus flares and
      maximum temperature increase (rho=0.87, p<0.001), minimum temperature increase
      (rho=0.87, p<0.001), and duration of sunshine increase (rho=0.78, p=0.003). These
      correlations were also observed in patients with renal flares. CONCLUSION: We
      confirmed a seasonal pattern for lupus flares among patients living in Southern
      France, with most flares in spring, in correlation with an increase in
      temperature and duration of sunshine. A similar seasonal pattern was observed in
      patients with no cutaneous involvement and with visceral involvement.

PMID- 22385884
TI  - Infectious complications of chemotherapy in clinically aggressive mature B and T
      cell lymphomas.
AB  - BACKGROUND: Scientific literature on infectious complications of chemotherapy in
      lymphomas is often based on retrospective studies or clinical trials performed
      with selected patients. This population may not be representative of the routine
      clinical practice. We aimed to analyse the incidence and type of infections
      associated to standard chemotherapy in clinically aggressive mature B and T cell
      lymphomas (AMBTL) and to detect baseline variables predictive of the risk of
      infection in a cohort of unselected patients. METHODS: A prospective
      observational study of all the patients treated with first line chemotherapy for
      AMBTL in our Lymphoma Unit, in the setting of a community based teaching
      hospital, was performed. The statistical methods were univariate and multivariate
      analyses. RESULTS: 183 infectious episodes were registered in 97 (49%) of the 198
      patients. Seventy-nine of them (43%) were associated to febrile neutropenia (27%
      of the patients). Microbiological documentation was obtained in 46% and only
      clinical documentation in 15%; 39% were classified as fever of unknown origin.
      Gram negative bacilli were the predominant aetiology. There were several
      variables related to risk of infection, but in multivariate analysis only a poor
      initial performance status was predictive of the risk of febrile neutropenia and
      infection during the first line chemotherapy. CONCLUSIONS: In our cohort of AMBTL
      patients treated with first line chemotherapy, more than half of the relevant
      infections occurred without febrile neutropenia. A poor performance status was
      the only independent variable associated with the risk of febrile neutropenia or
      infection in the course of first line chemotherapy.

PMID- 22385886
TI  - Can we consider the right hepatic lobe size/albumin ratio a noninvasive predictor
      of oesophageal varices in hepatitis C virus-related liver cirrhotic Egyptian
      patients?
AB  - BACKGROUND: The current guidelines recommend the screening of all cirrhotic
      patients by endoscopy, but repeated endoscopic examinations are unpleasant for
      patients and have a high cost impact and burden on endoscopic units. The aim of
      this study is to evaluate the optimal liver lobe size/albumin ratio and to
      compare this ratio with spleen size, platelet count and platelet count/spleen
      diameter ratio as potential noninvasive predictors of oesophageal varices in
      hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients. METHODS:
      This prospective study included one hundred patients with HCV-related liver
      cirrhosis. All studied subjects underwent a detailed clinical examination,
      biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound.
      The platelet count/spleen diameter ratio and the right liver lobe/albumin
      concentration ratio for all patients were calculated. RESULTS: The 4 predictors
      demonstrated a high statistically significant correlation with the presence and
      grade of oesophageal varices (P values<0.001). The platelet count/spleen diameter
      ratio had the highest accuracy, followed by the right liver lobe/albumin
      concentration ratio, spleen size and then platelet count. CONCLUSION: The use of
      the studied noninvasive predictors, especially the platelet count/spleen diameter
      ratio and the right liver lobe/albumin concentration ratio, can help physicians
      by restricting the use of endoscopic screening only to patients presenting a high
      probability of oesophageal varices. This is especially useful in clinical
      settings where resources are limited and endoscopic facilities are not present in
      all areas. Such is the case in Egypt, where there is a large number of patients
      who require oesophageal screening for oesophageal varices.

PMID- 22385885
TI  - The effects of low-dose fluvastatin and valsartan combination on arterial
      function: a randomized clinical trial.
AB  - BACKGROUND: Ageing progressively diminishes arterial functions, even in the
      absence of traditional risk factors. Our aim was to explore whether age-related
      arterial changes in middle-aged males could be reversed using short-term, low
      dose fluvastatin/valsartan combination intervention. METHODS: Forty apparently
      healthy, middle-aged males (43.3 +/- 5.8 years) were recruited in a double-blind,
      randomised intervention. Individuals received either 10mg fluvastatin/20mg
      valsartan daily or placebo over 30 days. The brachial artery flow mediated
      dilation (FMD), pulse wave velocity (PWV) and common carotid artery beta
      stiffness were assessed at baseline and after 30 days, and again 5-10 months
      after therapy discontinuation. RESULTS: Arterial function variables significantly
      improved after 30 days of intervention; FMD improved by 167.7% (P<0.001), PWV by
      10.9% (P<0.05) and beta-stiffness by 18.8% (P<0.01), whereas no changes were
      obtained in the placebo group. The favourable outcomes in the intervention group
      were accompanied by a significant decrease of high sensitivity-C reactive protein
      levels (1.8-fold; P<0.05). In contrast, lipids and blood pressure remained
      unchanged. Surprisingly, the beneficial arterial effects were still present to a
      substantial degree 7 months after completing intervention (remaining % of initial
      improvement: FMD 82.1%, PWV 69.5% and beta-stiffness 68.5%), but declined
      substantially after 10 months. CONCLUSION: Our results indicate that age-related
      arterial changes, at least in middle-aged males, can be reversed. Short-term
      treatment with a low-dose fluvastatin/valsartan combination resulted in a large
      and long lasting improvement of arterial function.

PMID- 22385887
TI  - High prevalence of polymorphism and low activity of thiopurine methyltransferase
      in patients with inflammatory bowel disease.
AB  - BACKGROUND: Gene polymorphism of thiopurine methyltransferase (TPMT) correlates
      with decreased enzyme activity which determines a significant risk of adverse
      effect reactions (ADR) in patients treated with thiopurines. The aim of this
      study was to investigate TPMT genotype and phenotype status in patients with
      inflammatory bowel diseases (IBD). METHODS: Fifty-one consecutive out-patients
      with IBD were genotyped for the following allelic variants: rs1800462 (referred
      as TPMT 2 allele), rs1800460 (referred as TPMT 3B allele), and 1142345 (referred
      as TPMT 3C allele). Red blood cell TPMT activity was measured using a competitive
      micro-well immunoassay for the semi-quantitative determination of TPMT activity
      in red blood cells (RBC) by means of a 6-MP substrate. RESULTS: Polymorphism of
      TPMT was found in 5 out of 51 patients (10%; 95% CI 2%-18%), three heterozygous
      and two homozygous carriers. Six patients (11.8%; 95% CI 2.4%-19.5%) displayed
      very low, 12 (23.5%; 95% CI 11.4%-34.5%) intermediate, and 33 (64.7%; 95% CI 52%
      78%) normal/high TPMT activity. There were no differences between TPMT genotype
      and phenotype groups according to age, type of disease, smoking, and chronic
      medications. A 71% (95% CI 61%-81%; kappa=0.45) concordance rate was found
      between genotype and phenotype status. Six out of 27 (22%) current or past users
      of azathioprine developed ADR, with three (50%) displaying TPMT genotype and/or
      phenotype alterations. CONCLUSION: Compared to the general population, IBD
      patients may have significantly higher prevalence of TPMT polymorphism and, even
      more, low activity. Phenotypic more than genotypic TPMT analysis could be useful
      to better manage IBD therapy with thiopurines.

PMID- 22385888
TI  - Mortality in Cushing's syndrome: a systematic review and meta-analysis.
AB  - CONTEXT: Data on mortality associated with Cushing's disease (CD) and Cushing's
      syndrome (CS) are scarce. OBJECTIVE: To perform a systematic review and meta
      analysis of mortality studies in patients with CD and CS secondary to a benign
      adrenal adenoma. DATA SOURCES: A search was performed in seven electronic
      databases. Sixty-six articles were retrieved for analysis and 7 included in the
      final study. The main outcome measure was standardized mortality ratio (SMR).
      STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Studies reporting
      SMR for patients diagnosed with CD and/or CS. Outcomes were stratified by subtype
      of Cushing's syndrome. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were
      appraised by two authors and were synthesized using a weighted estimate based on
      the standard error of the SMR. RESULTS: The weighted mean of SMR for patients
      with CD was 1.84 (95% confidence interval (CI): 1.28-2.65). CD patients with
      persistent disease after initial surgery had a SMR of 3.73 (95% CI: 2.31-6.01),
      whereas mortality of CD patients with initial remission did not differ
      significantly from the general population (SMR: 1.23 (95% CI: 0.51-2.97)). SMR
      for patients with a benign adrenal adenoma was 1.90 (95% CI: 0.93-3.91). Age, sex
      and observation time did not significantly impact mortality. CONCLUSIONS: CD as
      opposed to CS due to a benign adrenal adenoma is associated with an excess
      mortality, which is attributed to patients in whom initial surgical cure is not
      obtained. This underlines the importance of a rigorous and early follow-up of
      newly operated patients with CD.

PMID- 22385889
TI  - Hematocrit, urea and gender: the Hematocrit, Urea and GEnder formula for
      prognosing progressive renal failure in diabetic nephropathy.
AB  - OBJECTIVE: Diabetic nephropathy is a common cause of end stage renal disease.
      Notwithstanding, wide inter-individual variations in the speed of progression of
      diabetic nephropathy are frequent. We have used the score of the HUGE formula to
      predict progression of kidney disease in a group of diabetic nephropathy
      patients. DESIGN AND METHODS: The sample consisted of 84 type 2 diabetic
      patients. At treatment entry, the mean age was 62.1 +/- 12.5 years and 59.5% were
      male. Blood pressure was measured at office at each visit. Serum creatinine,
      urea, hematocrit and 24h proteinuria were analyzed every 6 months. HUGE score was
      calculated from gender, urea and hematocrit. RESULTS: Mean HUGE score was 0.99 +/
      3.88. Using as cut off point 1.5, those patients who had a score equal or higher
      (n=31) showed a bigger increase in serum creatinine after one year (41.8 +/-
      62.1%) than those subjects with score<1.5 (n=53) (18.7 +/- 38.6%, p=0.041). 5
      patients with low HUGE score reached end stage renal failure (9.4%) and 10
      patients in the high HUGE score group (32.3, p=0.008). When logistic regression
      analysis was performed only a HUGE score higher than 1.5 (p=0.003) and
      proteinuria higher than 2g/day (p=0.041) were independently associated to CRF
      progression (creatinine increment>25%). CONCLUSIONS: In diabetic nephropathy
      patients the HUGE equation may be useful to detect the subjects prone to
      progressive renal failure. Wider samples will be needed to confirm this finding
      and, most important, its applicability to other kinds of nephropathy.

PMID- 22385890
TI  - The role of radix hedysari polysaccharide on the human umbilical vein endothelial
      cells (HUVECs) induced by high glucose.
AB  - BACKGROUND: Diabetes mellitus can cause a wide variety of vascular complications
      and it is one of the major risk factors for cardiovascular diseases (CVD). High
      glucose can induce vascular endothelial cell apoptosis. In this study, we
      investigated the effect of radix hedysari polysaccharide (HPS) on the depression
      of apoptosis of human umbilical vein endothelial cells (HUVECs) induced by high
      glucose. METHODS: HUVECs were treated with media containing 30 mM glucose in the
      presence or absence of vitamin C or HPS. The level of intracellular reactive
      oxygen species (ROS) and apoptosis of HUVECs was measured with flow cytometry.
      Expression of c-Jun NH(2)-terminal kinase (JNK) and caspase-3 were testified by
      real-time quantitative RT-PCR and immunofluorescence. RESULTS: High glucose was
      capable of eliciting the overexpression of JNK during the treatment procedure.
      Moreover, we found that the caspase-3 became overexpressed in apoptosis induced
      by high glucose; HPS could inhibit apoptosis under high glucose and suppress the
      generation of ROS and the overexpression of JNK and caspase-3. The effect of HPS
      on ROS quenching, inhibition of JNK and caspase-3 overexpression at the
      concentration of 100 MUg/ml was similar to that of vitamin C at the concentration
      of 100 MUM. CONCLUSION: The findings of the present study may suggest that HPS
      play a protection role on HUVECs against apoptosis induced by high glucose.

PMID- 22385891
TI  - Limitations of gammaglutamyl transaminase as an indicator of biliary obstruction.

PMID- 22385892
TI  - Gammaglutamyl transaminase in biliary obstruction.

PMID- 22385893
TI  - Clinical trial data provides hope for attenuation of mucosal injury in coeliac
      disease.

PMID- 22385894
TI  - Pseudo-myelofibrosis: a new clinical entity.

PMID- 22385895
TI  - Did Lind perform a clinical trial of scurvy in 1747?

PMID- 22385897
TI  - Low dose or high dose of proton pump inhibitor for ulcer bleeding?

PMID- 22385898
TI  - Opportunities and challenges for community health centers in meeting women's
      health care needs.

PMID- 22385899
TI  - Pregnancy is a screening test for later life cardiovascular disease: now what?
      Research recommendations.

PMID- 22385900
TI  - National trends in health insurance coverage of pregnant and reproductive-age
      women, 2000 to 2009.
AB  - PURPOSE: Health insurance facilitates financial access to health services,
      including prenatal and preconception care. This study characterized changes in
      health insurance coverage among reproductive-age women in the United States from
      2000 to 2009. METHODS: Data from female respondents (ages 18-49) to the National
      Health Interview Surveys, 2000 to 2009 (n = 207,968), including those pregnant
      when surveyed (n = 3,204), were used in a repeated cross-sectional design.
      Changes over time were estimated using longitudinal regression models. MAIN
      FINDINGS: Of the reproductive-age women in this study, 25% were uninsured at some
      point in the prior year. Ten percent of pregnant women reported currently being
      uninsured, and 27% and 58% reported Medicaid coverage or private health
      insurance, respectively. Among women who were not pregnant, 19% were currently
      uninsured, 8% had Medicaid, and 68% had private coverage. From 2000 to 2009, an
      increasing percentage of reproductive-age women reported having gone without
      health insurance in the past year. Controlling for sociodemographic and health
      variables, the chances that a reproductive-age woman had been uninsured increased
      by approximately 1.5% annually (p < .001), and did not differ between pregnant
      women and those who were not pregnant. The odds that an insured pregnant woman
      had Medicaid coverage increased 7% per year over the study period (p < .001),
      whereas the odds of private coverage decreased. CONCLUSION: Reproductive-age
      women are increasingly at risk of being uninsured, which raises concerns about
      access to prenatal and preconception care. Among pregnant women, access to
      private health insurance has decreased, and state Medicaid programs have covered
      a growing percentage of women. Health reform will likely impact future trends.

PMID- 22385901
TI  - Offenders who are mothers with and without experience in prostitution:
      differences in historical trauma, current stressors, and physical and mental
      health differences.
AB  - BACKGROUND: Women offenders are a growing population in the criminal justice
      system; most are mothers. A subset of these women have a history of prostitution.
      Despite more recent research identifying the needs of women offenders who are
      mothers, those with and without experience in prostitution are still generally
      represented in the literature as a homogenous group. METHODS: This study examined
      the differences between mothers who indicated that they had engaged in
      prostitution with those who had not. The data were from a survey of offending
      mothers in a Midwestern city and was based on 889 respondents. Approximately 20%
      of the women indicated that they had engaged in prostitution at some point in
      their lives. FINDINGS: Mothers with histories of prostitution reported more
      exposure to violence, witnessing crime, living in areas with high drug activity,
      and having a higher rate of physical and mental health problems. CONCLUSIONS:
      Health care professionals who interact with mothers in the criminal justice
      system who have histories of prostitution should be careful to assess for a
      history of trauma and its psychological consequences. Along with increased health
      care needs, interventions are needed to help these women obtain basic needs such
      as stable housing outside of high crime and high drug-use areas and to receive
      targeted psychological services that respond to the unique trauma suffered by
      this subpopulation of offenders.

PMID- 22385902
TI  - The role of epidemiology in improving the evidence base in injury prevention and
      trauma care.

PMID- 22385903
TI  - Can handheld micropower impulse radar technology be used to detect pneumothorax?
      Initial experience in a European trauma centre.
AB  - BACKGROUND: Pneumothoraces are a common injury pattern in emergency medicine.
      Rapid and safe identification can reduce morbidity and mortality. A new handheld,
      battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland,
      OH, USA), using micropower impulse radar (MIR) technology, has recently been
      introduced in Europe for the rapid and reliable detection of PTX. However, this
      technology has not yet been tested in trauma patients. This is the first quality
      control evaluation to report on emergency room performance of a new device used
      in the trauma setting. MATERIAL AND METHODS: This study was performed at a Level
      I trauma centre in Switzerland. All patients with thoracic trauma and undergoing
      chest X-ray and CT-scan were eligible for the study. Readings were performed
      before the chest X-ray and CT scan. The patients had eight lung fields tested
      (four on each side). All readings with the Pneumoscan were performed by two
      junior residents in our department who had previously received an instructional
      tutorial of 15min. The qualitative MIR results were blinded, and stored on the
      device. We then compared the results of the MIR to those of the clinical
      examination, chest X-ray and CT-scan. RESULTS: 50 patients were included, with a
      mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT;
      six of these were detected by Pneumoscan, leading to an overall sensitivity of
      85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found
      during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7
      71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX
      was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7
      99.9)%. DISCUSSION: The Pneumoscan is an easy to use handheld technology with
      reliable results. In this series, the sensitivity to detect a PTX by the
      Pneumoscan was higher than by clinical examination and chest X-ray. Further
      studies with higher case numbers and a prospective study design are needed to
      confirm our findings.

PMID- 22385904
TI  - Biosynthesis of rhodiocyanosides in Lotus japonicus: rhodiocyanoside A is
      synthesized from (Z)-2-methylbutanaloxime via 2-methyl-2-butenenitrile.
AB  - Lotus japonicus contains the two cyanogenic glucosides, linamarin and
      lotaustralin, and the non cyanogenic hydroxynitriles, rhodiocyanoside A and D,
      with rhodiocyanoside A as the major rhodiocyanoside. Rhodiocyanosides are
      structurally related to cyanogenic glucosides but are not cyanogenic. In vitro
      administration of intermediates of the lotaustralin pathway to microsomes
      prepared from selected L. japonicus accessions identified 2-methyl-2
      butenenitrile as an intermediate in the rhodiocyanoside biosynthetic pathway. In
      vitro inhibitory studies with carbon monoxide and tetcyclacis indicate that the
      conversion of (Z)-2-methylbutanal oxime to 2-methyl-2-butenenitrile is catalyzed
      by cytochrome P450(s). Carbon monoxide inhibited cyanogenic glucosides as well as
      rhodiocyanosides synthesis, but inhibition of the latter pathway was much
      stronger. These results demonstrate that the cyanogenic glucoside and
      rhodiocyanosides pathways share CYP79Ds to obtain (Z)-2-methylbutanaloxime from l
      isoleucine, whereas the subsequent conversions are catalyzed by different P450s.
      The aglycon of rhodiocyanoside A forms the cyclic product 3-methyl-2(5H)
      furanone. Furanones are known to possess antimicrobial properties indicating that
      rhodiocyanoside A may have evolved to serve as a phytoanticipin that following
      beta-glucosidase activation and cyclization of the aglycone formed, give rise to
      a potent defense compound.

PMID- 22385905
TI  - Migrant's access to immunization in Mediterranean Countries.
AB  - Countries bordering the Mediterranean are part of a major migration system. The
      aim of this study is to assess the main access barriers to immunization of mobile
      populations in the region and propose an action based framework to decrease
      health access inequalities. A survey on formal and informal barriers to
      immunization among mobile communities was conducted among public health officials
      formally appointed as focal points of the EpiSouth Network by 26 Mediterranean
      countries. Twenty-two completed the questionnaire. Thirteen countries reported at
      least one vaccine preventable disease (VPD) outbreak occurring among mobile
      populations since 2006 even though their legal entitlement to immunization is
      mostly equivalent to the general population's. Informal barriers, particularly
      lack of information and lack of trust in authorities, and disaggregation of data
      collection are the major issues still to be addressed. Mediterranean countries
      need to fill the gap in immunization coverage among pockets of susceptible
      individuals in order to prevent VPD outbreaks. Having for the most part ensured
      free entitlement, introducing more migrant friendly approaches, increasing
      information availability among mobile communities, building trust in public
      health services and disaggregating data collection to monitor and evaluate
      service performance among mobile groups are key aspects to address in the region.

PMID- 22385906
TI  - A demographic survey of unwanted horses in Ireland 2005-2010.
AB  - BACKGROUND: The Irish Horse Industry expanded during the Celtic Tiger boom years,
      then contracted in the current economic recession. High value horses were
      traditionally controlled through sale at public auction, private sales and sales
      to dealers; these are now also being reduced by decreases in production (> 40%),
      and increases in retirement, re-homing, euthanasia and disposal through Category
      2 plants and abattoirs. The absence or banning of horse abattoirs has been shown
      to have very significant welfare social and economic consequences in the USA.
      This study described the currently available data on the demographics of unwanted
      horses in Ireland from 2005 to 2010. RESULTS: The majority of horses euthanised
      by practicing veterinarians are destroyed on medical grounds but the number
      euthanised at the request of welfare groups and the state, as well as welfare
      related calls and the number of horses involved in these calls and subsequent
      visits is increasing reflecting the increasing involvement of the veterinary
      profession in equine welfare. Welfare groups have limited resources and do not
      have a tradition of recording data, but they too have reported increasing calls,
      visits and numbers of horses per visit. Welfare groups provide significant
      service to equine welfare and the community. Local Authorities report similar
      trends. Over 300 horses were found dead or required immediate or subsequent
      euthanasia following welfare group and local authority visits in 2010, which is
      of national concern. The majority of local authority interfaces with unwanted
      horses are with urban (60%) rather than rural (40%) horses. Mortality figures are
      poor indicators of non-fatal neglect. More horses were admitted into the care of
      local authorities than welfare groups, reflecting significant state and taxpayer
      investment in the control of low value horses. Category 2 plants and abattoirs
      represent a significant state investment in licensing and control in the national
      interest. Abattoirs provide an increasingly important and essential service for
      the disposal of unwanted horses. Despite the increase in unwanted horses, Ireland
      is a minority contributor to the EU slaughter total. CONCLUSIONS: There is a need
      for annual demographic data compilation and review of the numbers of unwanted
      horses and ponies within the horse industry to assist policy makers and
      legislators.

PMID- 22385907
TI  - Fluoroquinolone-resistant extraintestinal Escherichia coli clinical isolates
      representing the O15:K52:H1 clonal group from humans and dogs in Australia.
AB  - Antimicrobial-resistant extraintestinal pathogenic Escherichia coli (ExPEC)
      impact both human and veterinary medicine. One ExPEC clonal group that has become
      increasingly multidrug-resistant is serotype O15:K52:H1. Accordingly, we sought
      O15:K52:H1 strains among fluoroquinolone-resistant (FQ(r)) E. coli clinical
      isolates from humans (n=582) and dogs (n=120) in Australia. The phylogenetic
      group D isolates (267/702; 38%) were screened for O15:K52:H1-specific single
      nucleotide polymorphisms (SNPs) in fumC and the O15 rfb variant. The 34 so
      identified O15:K52:H1 isolates (33 human, 1 canine) underwent antimicrobial
      susceptibility profiling, virulence genotyping, and macrorestriction profiling.
      Although susceptibility profiles varied, the 34 isolates were closely related by
      pulsed-field gel electrophoresis and exhibited typical O15:K52:H1-associated
      virulence profiles (complete pap operon, F16 papA allele, papG allele II, iha,
      fimH, sat, fyuA, iutA, kpsMII, ompT). The canine isolate closely resembled human
      isolates. Thus, O15:K52:H1 strains contribute to the FQ(r) ExPEC population in
      Australia and may potentially be transferred between humans and dogs.

PMID- 22385908
TI  - Blocking effect of twin boundaries on partial dislocation emission from void
      surfaces.
AB  - Recent discovery that nanoscale twin boundaries can be introduced in ultrafine
      grained metals to improve strength and ductility has renewed interest in the
      mechanical behavior and deformation mechanisms of these nanostructured materials.
      By controlling twin boundary spacing, the effect of twin boundaries on void
      growth is investigated by using atomistic simulation method. The strength is
      significantly enhanced due to the discontinuous slip system associated with these
      coherent interfaces. Atomic-scale mechanisms underlying void growth, as well as
      the interaction between twin boundaries and the void, are revealed in details.

PMID- 22385909
TI  - Investigating the ecology and evolution of cryptic marine nematode species
      through quantitative real-time PCR of the ribosomal ITS region.
AB  - The presence of morphologically similar but genetically distinct species has
      impacted biogeographical and ecological paradigms. In marine sediments, free
      living nematodes form one of the most abundant and diverse faunal groups.
      Inferring the importance of nematode diversity for ecosystem functioning requires
      species-level identification, which is hampered by the lack of easily observable
      diagnostic characters and the presence of cryptic species. New techniques are
      urgently needed to adequately study the ecology and evolution of cryptic species.
      The aim of the present study was to evaluate the potential of a quantitative real
      time PCR (qPCR) assay using the internal transcribed spacer (ITS) region of the
      ribosomal DNA to detect and quantify cryptic species of the R. (P.) marina
      complex. All primer pairs proved to be highly specific, and each primer pair was
      able to detect a single juvenile in a pool of 100 nematodes. C(t)  values were
      significantly different between developmental stages for all species except for
      PmIII. Despite differences between developmental stages, a strong correlation was
      observed between the amount of extracted DNA and the number of nematodes present.
      Relative and absolute quantification estimates were comparable and resulted in
      strong positive correlations between the qPCR estimate and the actual number of
      nematodes present in the samples. The qPCR assay developed here provides the
      ability to quickly identify and quantify cryptic nematode species and will
      facilitate their study in laboratory and field settings.

PMID- 22385911
TI  - Factors influencing Ghanaian midwifery students' willingness to work in rural
      areas: a computerized survey.
AB  - BACKGROUND: Lack of midwives in rural and remote areas of Ghana is a national
      concern as the country attempts to reach targets set by Millennium Development
      Goals to reduce maternal and child mortality by 2015. OBJECTIVES: To understand
      factors influencing third-year Ghanaian midwifery students' willingness to work
      in rural areas. SETTING: Two of the largest midwifery schools in Ghana.
      PARTICIPANTS: Third-year midwifery students (n=238) about to graduate and enter
      the workforce. METHODS: Based on focus group discussions with midwifery students,
      we refined a computerized survey to assess students' preferences for rural
      posting after graduation. We then administered this survey to midwifery students
      in Ghana. We used Pearson's chi-squared to compare the top reasons for choosing
      job location between those students likely and not likely to work in a rural
      area. Logistic regression models were used to calculate the odds ratios. RESULTS:
      An opportunity to gain additional education was the most important factor for the
      midwifery students in deciding where they would eventually work (72%). Poor
      quality of clinical facilities (26%), poor quality of education for children
      (19%), and lack of social amenities (17%) were major deterrents to working in
      rural communities. For student midwives willing to work in rural areas the top
      reasons cited included to serve humanity (74%), and increased opportunities to
      gain clinical experience (62%). More experiences overall with rural communities
      resulted in greater odds of being willing to work in a rural area. Being born in
      a rural area (OR: 1.95, 95% CI: 0.736, 5.16) and living in a rural area after age
      5 for one-year or more (OR: 1.52, CI: 0.857, 2.70). An exception to this was
      midwifery students who performed health work for six weeks or more in a rural
      area during training. These students were found to have 0.83 lower odds of
      willingness to work in a rural area (95% CI: 0.449, 1.55). CONCLUSION: By better
      understanding the motivating factors for rural healthcare workers, specific
      policy interventions can be established to improve the distribution of midwives
      thereby decreasing the burden of maternal and infant mortality.

PMID- 22385910
TI  - A high affinity, antidote-controllable prothrombin and thrombin-binding RNA
      aptamer inhibits thrombin generation and thrombin activity.
AB  - BACKGROUND: The conversion of prothrombin to thrombin is one of two non
      duplicated enzymatic reactions during coagulation. Thrombin has long been
      considered an optimal anticoagulant target because it plays a crucial role in
      fibrin clot formation by catalyzing the cleavage of fibrinogen, upstream
      coagulation cofactors and platelet receptors. Although a number of anti-thrombin
      therapeutics exist, it is challenging to use them clinically due to their
      propensity to induce bleeding. Previously, we isolated a modified RNA aptamer
      (R9D-14) that binds prothrombin with high affinity and is a potent anticoagulant
      in vitro. OBJECTIVES: We sought to explore the structure of R9D-14 and elucidate
      its anticoagulant mechanism(s). In addition to designing an optimized aptamer
      (RNA(R9D-14T)), we also explored whether complementary antidote oligonucleotides
      can rapidly modulate the optimized aptamer's anticoagulant activity. METHODS AND
      RESULTS: RNA(R9D-14T) binds prothrombin and thrombin pro/exosite I with high
      affinity and inhibits both thrombin generation and thrombin exosite I-mediated
      activity (i.e. fibrin clot formation, feedback activity and platelet activation).
      RNA(R9D-14T) significantly prolongs the aPTT, PT and TCT clotting assays, and is
      a more potent inhibitor than the thrombin exosite I DNA aptamer ARC-183.
      Moreover, a complementary oligonucleotide antidote can rapidly (< 2 min) and
      durably (>2 h) reverse RNA(R9D-14T) anticoagulation in vitro. CONCLUSIONS:
      Powerful anticoagulation, in conjunction with antidote reversibility, suggests
      that RNA(R9D-14T) may be ideal for clinical anticoagulation in settings that
      require rapid and robust anticoagulation, such as cardiopulmonary bypass, deep
      vein thrombosis, stroke or percutaneous coronary intervention.

PMID- 22385912
TI  - Medication communication between nurses and patients during nursing handovers on
      medical wards: a critical ethnographic study.
AB  - BACKGROUND: Communication is central to safe medication management. Handover is a
      routine communication forum where nurses provide details about how patients'
      medications are managed. Previous studies have investigated handover processes as
      general communication forums without specific focus on medication information
      exchange. The effects of social, environmental and organisational contexts on
      handover communication and medication safety have not been explored. OBJECTIVES:
      To examine dominant and submissive forms of communication and power relations
      surrounding medication communication among nurses, and between nurses and
      patients during handover. DESIGN: A critical ethnographic approach was utilised
      to unpack the social and power struggles embedded in handover practices.
      SETTINGS: The study was conducted in two medical wards of a metropolitan teaching
      hospital in Melbourne, Australia from January to November 2010. PARTICIPANTS: All
      registered nurses employed in the medical wards during the study time were
      eligible for participation. Patients were eligible if they were able to
      communicate with nurses about how their medications were managed. In total, 76
      nurses and 27 patients were recruited for the study after giving written consent
      for participation. METHODS: Participant observations, field interviews, video
      recordings and video reflexive focus groups were conducted. Fairclough's critical
      discourse analytic framework guided data analysis. RESULTS: Nurse coordinators'
      group handovers in private spaces prioritised organisational and biomedical
      discourses, with little emphasis on evaluating the effectiveness of medication
      treatment. The ward spatial structure provided an added complexity to how staff
      allocation occurred. Handovers involving patients in the public spaces at the
      bedside facilitated a partnership model in medication communication. Nurses
      exercised discretion during bedside handovers by discussing sensitive information
      away from the bedside. Handovers across different wards during patient transfers
      caused communication breakdowns because information was not exchanged between
      bedside nurses. CONCLUSIONS: Nurse coordinators need to relinquish organisational
      control of the handover practice and appreciate the contribution of bedside
      nurses to patient information exchange. Bedside nurses need to be provided with
      opportunities to raise questions during the group handover. Designated meeting
      spaces need to be provided to reduce interruptions to the group handover process.

PMID- 22385913
TI  - Effectiveness of non-pharmacological interventions for the prevention of
      bloodstream infections in infants admitted to a neonatal intensive care unit: A
      systematic review.
AB  - BACKGROUND: Bloodstream infections are associated with increased morbidity and
      mortality in very low birth weight infants admitted to neonatal intensive care
      units. OBJECTIVE: To evaluate the available evidence for the effectiveness of non
      pharmacological bloodstream infection-preventive measures in infants admitted to
      a neonatal intensive care unit. DESIGN: A systematic review of randomized,
      controlled trials, controlled clinical trials, interrupted time series and
      pretest-posttest studies. DATA SOURCES: PubMed, CINAHL, Web-of-Science, Cochrane
      Central Register of Controlled Trials, and Embase were searched. REVIEW METHODS:
      The systematic review was carried out according to the guidelines of the Center
      for Reviews and Dissemination. The methodological quality of the individual
      studies was evaluated with the quantitative evaluation form of McMaster
      University. The review included randomized, controlled trials, controlled
      clinical trials, interrupted time series, and pre-posttest studies published from
      January 1990 to January 2011. Quantitative pooling of the results was not
      feasible due to the high heterogeneity of the interventions, methods and outcome
      measures. Instead, we present the studies in tabular form and provide a narrative
      account of the study characteristics and results. RESULTS: Fifteen studies out of
      288 generated hits were selected and categorized as research on: hand hygiene
      (5), intravenous (IV) bundles (4), closed IV sets/patches/filters (4),
      surveillance (1), and percutaneously inserted central catheter teams (1). IV
      bundles including proper insertion and proper maintenance showed to be the most
      effective intervention for preventing bloodstream infection in infants; in three
      out of four studies on IV bundles, a statistically significant reduction of
      bloodstream infections was mentioned. CONCLUSIONS: Although the methodological
      quality of most studies was not very robust, we conclude that IV bundles may
      decrease bloodstream infections in infants. However, differences in IV bundle
      components and in practices limited the underpinning evidence. There is limited
      evidence that the introduction of a percutaneously inserted central catheter team
      results in bloodstream infection reduction. Hand hygiene promotion increases hand
      hygiene among healthcare workers, but there is inconclusive evidence that this
      intervention subsequently leads to a bloodstream infection reduction in infants.
      Future studies must be well designed, with standardized outcome measures.

PMID- 22385914
TI  - From 'conductor' to 'second fiddle': older adult care recipients' perspectives on
      transitions in family caring at hospital admission.
AB  - BACKGROUND: Family carers provide strong support for many older adults, often
      enabling older adults to remain at home. Little is known about the care
      recipients' perspectives of the role and contributions of family carers,
      particularly when hospital admissions occur as part of end of life care. AIM:
      This paper explores the meanings of family caring for care recipients by drawing
      on older adults' perspectives about the impact of hospital admission on
      established family caring relationships. DESIGN: Exploratory semi-structured
      qualitative interviews. Key findings reported in this paper emerged from within
      the inductive research design. SETTING: Interviews were conducted in older
      adults' place of residence in northwest England between June 2009 and July 2010.
      PARTICIPANTS: Participants were 27 older adults living with heart failure (n=13)
      or lung cancer (n=14), aged 69-89 years (mean 79 +/- 4.3 years) and considered by
      their health professionals to be in their last year of life. In 12 of the
      interviews, a family carer was also present and made contributions. FINDINGS: For
      community-dwelling older adults, family carers are conceptualised as
      'conductors'; making strong contributions to maintaining the rhythm of good care
      throughout the illness trajectory. Following older adults' hospital admission,
      family carers find themselves in the role of 'second fiddle', their ability to
      work with the individual and to make or influence decisions vastly reduced.
      Despite this, carers continue to invest considerable effort in maintaining
      continuity in the carer relationship to maximise the individual's wellbeing by
      identifying needs, filling gaps in provision and advocating on patients' behalf.
      Family carers act flexibly to provide continuity, support and take responsibility
      for older adults' wellbeing across settings. CONCLUSIONS: Nurses and family
      carers working together, and greater appreciation of the contribution and role of
      family carers by health professionals may contribute to improving the quality and
      continuity of care for older adults.

PMID- 22385915
TI  - Introduction: towards predicting outcome of radiotherapy-at last.

PMID- 22385916
TI  - Genome-wide association studies and prediction of normal tissue toxicity.

PMID- 22385917
TI  - Predictive factors for local recurrence in breast cancer.
AB  - Risk factors for local recurrence in breast cancer after breast conserving
      therapy (BCT) differ from those for local recurrence after mastectomy. To better
      guide optimal treatment of individual patients, it is desirable to identify
      patients at high risk for local recurrence. Several clinical and histopathologic
      factors, such as young age and presence of ductal carcinoma in situ, are known to
      be predictors for local recurrence after BCT. After mastectomy, lymph node status
      and tumor size are dominant risk factors for local recurrence. The results of
      recent expression profiling studies have explained differences in prognosis and
      risk for local recurrence and also explained response to different therapies
      (adjuvant systemic therapy and radiotherapy). Because of the variation in
      different subtypes of breast cancer and the difference in amount of tumor burden
      remaining after surgery, finding robust predictive profiles is complex. In this
      review, we describe the predictive and prognostic factors for local recurrence
      after mastectomy and BCT and also describe the role of radiosensitivity in local
      recurrence.

PMID- 22385918
TI  - Predicting recurrence after radiotherapy in head and neck cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide. Radiotherapy is a mainstay of treatment, either alone for early stage
      tumors or combined with chemotherapy for late stage tumors. An overall 5-year
      survival rate of around 50% for HNSCC demonstrates that treatment is often
      unsuccessful. Prediction of outcome is, therefore, aimed at sparing patients from
      ineffective and toxic treatments on the one hand, and indicating more successful
      treatment modalities on the other. Both functional and genetic assays have been
      developed to predict intrinsic radiosensitivity, hypoxia, and repopulation rate.
      Few, however, have shown consistent correlations with outcome across multiple
      studies. Messenger RNA and microRNA profiling show promise for predicting
      hypoxia, whereas epidermal growth factor receptor expression combined with other
      measures of tumor differentiation grade shows promise for predicting repopulation
      rate. Intrinsic radiosensitivity assays have not proven useful to date, although
      development of repair protein foci assays indicates promise from preclinical
      studies. Assays for cancer stem cell content have shown promise in several
      clinical studies. In addition, 2 assays showing robustness as predictors for
      outcome in HNSCC are human papilloma virus status and epidermal growth factor
      receptor expression. Neither these nor stem cell assays, however, can as yet
      reliably indicate alternative and better treatments for poor prognosis patients.
      It would be of great value to have assays that predict the benefit for an
      individual from combining new molecularly targeted agents with radiotherapy to
      increase response, in particular those that exploit tumor mutations to provide
      tumor specificity. Predictive assays are being developed for detecting defects in
      repair pathways for single- and double-strand DNA breaks, which should allow
      selection of drugs targeting the appropriate backup pathway, thus exploiting the
      concept of synthetic lethality. This is one of the most promising areas for
      prediction, both currently and in the future.

PMID- 22385919
TI  - Hypoxia gene expression signatures as prognostic and predictive markers in head
      and neck radiotherapy.
AB  - Reliable methods for identification of hypoxia in radiotherapy-treated tumors
      have been a desirable aim in radiation oncology for decades. Hypoxia is a common
      feature of the microenvironment in solid tumors, and it is associated with
      increased aggressiveness, reduced therapeutic response, and a poorer clinical
      outcome. In head and neck squamous cell carcinomas, the negative effect of
      hypoxia on radiotherapeutic response can be counteracted and minimized by
      applying hypoxic modification to radiotherapy, which favors the clinical outcome
      after treatment. However, not all tumors are hypoxic, hence not all patients
      benefit from the addition of hypoxic modification. Therefore, predictive and
      clinically applicable methods for pretherapeutic hypoxic evaluation and
      categorization are needed. Hypoxia gene expression signatures are a developing
      strategy to approach this obstacle. This method has evolved along with the
      development of complementary DNA microarray analysis and classifies tumors in
      accordance to the expression of specific hypoxia-responsive genes in the tumor
      biopsy. Thus, tumors are classified and categorized in terms of the biological
      behavior to hypoxic conditions in the microenvironment. Until now, most of the
      developed hypoxia signatures have only been evaluated in terms of their
      prognostic impact; however, recently, a predictive impact for hypoxic
      modification of radiotherapy was verified. Here, we provide an overview of the
      hypoxic issue in radiotherapy and present the most promising hypoxia gene
      expression signatures developed to date.

PMID- 22385920
TI  - Human papillomavirus as a marker of the natural history and response to therapy
      of head and neck squamous cell carcinoma.
AB  - There has been a gradual change in the demographics of head and neck carcinoma.
      Although relatively uncommon, the incidence of oropharyngeal carcinoma has been
      increasing despite declining tobacco consumption and contrary to a diminishing
      incidence of cancers at other head and neck sites. It is now clear that the
      incidence of human papillomavirus (HPV)-associated oropharyngeal cancers is
      rising, likely as a consequence of changing life styles and sexual behaviors.
      Many studies have contributed to understanding the characteristics of HPV-related
      oropharyngeal carcinoma, which usually presents as nonkeratinizing squamous cell
      carcinoma of low to intermediate T-category and affects middle-aged white men,
      having higher socioeconomic status and no or brief history of tobacco
      consumption. The diagnosis of this distinct neoplastic entity can be firmly
      established by a combination of p16 immunohistochemical and in situ hybridization
      assays. Compared with the traditional smoking-associated head and neck squamous
      cell carcinoma, HPV-related oropharyngeal carcinoma has a favorable natural
      history and responds better to treatment. Consequently, patients with this cancer
      have better long-term survival than those with HPV-unrelated head and neck
      squamous cell carcinoma (eg, 5-year overall survival rate of >80% versus ~40% for
      patients with stage III-IV tumors), and hence they are more likely to experience
      chronic therapy-induced morbidity. Therefore, changes in evaluation, staging, and
      treatment are needed for this patient group. However, attempts to change the
      treatment for HPV-associated oropharyngeal carcinoma should take place in a
      closely monitored clinical trial setting. In this article, we summarize the
      epidemiology, diagnosis, and clinical behavior of HPV-associated oropharyngeal
      carcinoma, with emphasis on prognostic and biomarker discovery aspects, and
      discuss briefly the current thoughts on changing the treatment paradigms aimed at
      reducing morbidity while preserving the high tumor control probability through
      well-coordinated prospective trials.

PMID- 22385921
TI  - Biological predictors of cervical cancer response to radiation therapy.
AB  - The addition of cisplatin-based chemotherapy to standard radiation therapy
      reduces the risk of recurrence and disease-related death rates from locally
      advanced cervical cancers by as much as 50%. However, the absolute gains are
      relatively small for patients with early tumors, many of whom would have been
      cured with radiation alone, and recurrence rates are still high for patients who
      have very large or advanced-stage tumors. As a result, there is a pressing need
      for more accurate predictors of radiocurability. A variety of types of biomarkers
      have been shown to correlate with cervical cancer response to radiation therapy.
      These include traditional clinical and morphologic predictors, non-molecular
      biomarkers, including hypoxia and fluorodeoxyglucose-positron emission tomography
      (FDG-PET) avidity, as well as molecular biomarkers, which include single-gene
      markers or array-based multigene predictors. Multi-gene predictors of response
      remain immature in cervical cancer, but studies thus far have paved the way for
      future studies to validate these findings. Methods will need to be standardized
      and markers will need to be validated on homogeneous patient populations and
      treatment approaches before they can become useful tools for clinical decision
      making. In addition, new biomarkers will be of major value only if they add to
      the predictive value of traditional clinical and morphologic predictors.
      Ultimately, the most useful biomarkers will identify patients who will benefit
      from specific molecularly targeted agents in addition to radiation therapy or
      perhaps identify patient who are at low risk for recurrence, for whom the dose of
      radiation or chemotherapy can be reduced.

PMID- 22385922
TI  - Cancer stem cells as a predictive factor in radiotherapy.
AB  - Cancer stem cell research is one of the most thriving and competitive areas in
      oncology research because it has the potential to dramatically affect clinical
      outcomes. Led by progress in hematology, cancer stem cell research has now
      provided evidence to play an important role for solid cancers as well. Because
      radiotherapy is only second to surgery in terms of its curative potency, it is
      very important for radiation oncologists to learn whether progress in cancer stem
      cell biology can enable them to exploit this knowledge to help cure more patients
      suffering from cancer. The present article gives an overview about the challenges
      of the cancer stem cell concept and highlights some important phenomena that are
      under intense investigation, such as phenotypic plasticity of stemness and impact
      and dynamics of microenvironmental niches. We discuss the potential and
      limitations of current experimental and theragnostic tools and end up with an
      agenda for future research as outlook for translational possibilities in the
      clinic.

PMID- 22385923
TI  - Prediction in rectal cancer.
AB  - The treatment of rectal cancer largely depends on disease stage at diagnosis,
      based on which patients can be classified as low, intermediate, or high risk.
      Prognostic and predictive markers, specific to each risk category, can be applied
      for optimal risk classification and subsequent treatment allocation. These
      markers are either histopathological, determined with imaging, or have a
      biomolecular background. This review provides an overview of the current status
      of treatment options and the use of prognostic and predictive markers in each
      risk category. An effort was made to identify those markers that are currently
      lacking in, but have the potential to improve, the clinical decision process by
      discussing the data from recent studies aimed at the development of new
      prognostic and predictive markers. At this moment, none of the markers studied
      has been proven to be of significant, independent value, justifying
      implementation in daily clinical practice. However, recent developments in
      imaging techniques and biomolecular research do show great potential.

PMID- 22385924
TI  - Characteristics of a population-wide sample of smokers recruited proactively for
      the ESCAPE trial.
AB  - OBJECTIVES: To describe the characteristics of a sample of smokers recruited
      proactively into a smoking cessation trial, and to compare these characteristics
      with the wider population using data from the General Household Survey (GHS) and
      National Statistics Omnibus Survey. STUDY DESIGN: Sample recruited for a
      randomized controlled trial. METHODS: Between August 2007 and October 2008, 123
      general practices mailed questionnaires to smokers in the U.K. identified from
      computer records. Smokers willing to participate in a trial of personalized
      computer-tailored feedback returned the questionnaires to the research team. The
      characteristics of the sample were compared with the wider population using data
      from the GHS and National Statistics Omnibus Survey, and Index of Material
      Deprivation scores. RESULTS: A response rate of 11.4% (n = 6697) was achieved.
      The sample was demographically similar to the population sample, with an even
      distribution of participants from areas of both high and low deprivation. The
      sample was more dependent than the GHS sample, but less dependent than clinic
      samples. Distribution by motivation and readiness to quit was similar to
      population estimates. CONCLUSIONS: Public health strategies targeting the entire
      population of smokers are needed to counter the low recruitment rates resulting
      from the traditional reactive methods of recruitment to smoking cessation
      studies. Using computerized records to identify and contact patients who are
      smokers is a simple method of recruiting a larger, more representative sample of
      smokers.

PMID- 22385925
TI  - ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non
      small cell lung cancer with leptomeningeal carcinomatosis.
AB  - Anaplastic lymphoma kinase (ALK) inhibitor has shown dramatic efficacy in non
      small cell lung cancer (NSCLC) patients harboring ALK rearrangements in phase I
      trial. Herein we report two cases of NSCLC patients with leptomeningeal
      carcinomatosis (LM), treated with ALK inhibitor under emergent use of
      investigational new drug combined with intrathecal methotrexate treatment.
      Progression free survival was 10 months and 6 months, respectively, and little
      additional toxicities were observed. These results suggest that ALK inhibitor
      might be safely administered even in patients or those with metastases in central
      nervous system.

PMID- 22385926
TI  - Applying Best-Worst scaling methodology to establish delivery preferences of a
      symptom supportive care intervention in patients with lung cancer.
AB  - BACKGROUND: Delivering a non-pharmacological symptom management intervention in
      patients with lung cancer is often challenging due to difficulties with
      recruitment, high attrition rates, high symptom burden, and other methodological
      problems. The aim of the present study was to elicit quantitative estimates of
      utility (benefit) associated with different attribute levels (delivery options)
      of a symptom management intervention in lung cancer patients. METHODS: An
      application of Best-Worst scaling methodology was used. Effects (attributes)
      tested included the location of the intervention (home or hospital), type of
      trainer (health professional or trained volunteer), caregiver involvement or not,
      and intervention delivered individually or in groups of patients. Participants
      were asked to evaluate and compare their preferences (utilities) towards the
      different attribute levels within scenarios and select the pair of attribute
      levels that they consider to be furthest apart. RESULTS: Eighty-seven patients
      with lung cancer participated. The most important preferences for an intervention
      included the location (being delivered at home) and delivered by a health care
      professional. The least important preference was the involvement of a caregiver.
      Gender had an effect on preferences, with females being less inclined than men to
      prefer to receive an intervention in the home than the hospital and less inclined
      than men to have no other patients present. Furthermore, older participants and
      those in advanced stages of their disease were less inclined to have no other
      patients present compared to younger participants and those with earlier stages
      of disease, respectively. CONCLUSION: Considering patient preferences is an
      important step in developing feasible, patient-centred, appropriate and
      methodologically rigorous interventions and this study provided indications of
      such patient preferences.

PMID- 22385927
TI  - Segmental bioimpedance for measuring amlodipine-induced pedal edema: a placebo
      controlled study.
AB  - BACKGROUND: The development of antihypertensives requires efficient and accurate
      tools for identifying pedal edema. Methodologies used to gauge the potential of
      an agent to induce pedal edema in short-term (<4-week) clinical trials have not
      been reported in the literature. OBJECTIVE: The purpose of this study was to
      identify a robust and practical method for measuring drug-induced pedal edema for
      use in the clinical development of antihypertensives. The efficacy of segmental
      bioimpedance in the detection of increased pedal edema was compared with that of
      clinical pitting assessment, ankle circumference, and water displacement
      volumetry. METHODS: The study population consisted of male and female healthy
      subjects and patients with stage 1 or 2 hypertension who were otherwise healthy.
      Participants were randomly assigned to receive amlodipine 10 mg or placebo once
      daily in this 6-week, double-blind, parallel-group study. Amlodipine was used as
      a means of inducing ankle edema, and not for the treatment of hypertension.
      Patients with hypertension were required to undergo a washout of antihypertensive
      therapies. Edema was evaluated using segmental bioimpedance at 10 kHz, clinical
      pitting assessment, ankle circumference, and water displacement at weeks 2, 4,
      and 6. The ANOVA model used included treatment and baseline values as covariates,
      with treatment pairs compared via t tests derived from the model. RESULTS: A
      total of 47 individuals were randomized (49% male; 29 [62%] with hypertension;
      mean [SD] age, 59 [5.9] years; baseline body mass index, 28.6 kg/m(2) [2.8];
      blood pressure 146.6 [10.7]/93.5 [6.5] and 139.3 [8.3]/89.5 [4.5] in individuals
      with and without hypertension, respectively; amlodipine 10 mg, n = 24; placebo, n
      = 23). At weeks 2, 4, and 6, statistically significant treatment differences in
      changes from baseline were detected using water displacement (mean [90% CI]
      treatment differences, +39.0 g [+17.9 to +60.1], +61.9 g [+36.1 to +87.6], and
      +72.2 g [+42.3 to +102.1], respectively; all, P <= 0.001), ankle circumference
      (+4.74 mm [+2.38 to +7.11; P < 0.001], +2.92 mm [+0.33 to +5.49; P = 0.032], and
      +5.16 mm [+2.21 to +8.11; P = 0.002]), and bioimpedance (-11.7 Omega [-18.1 to 
      5.4], -18.3 Omega [-26.2 to -10.4], and -20.9 Omega [-29.7 to -12.0]; all,
      P<=0.001), but no significant differences were detected using clinical assessment
      of pitting. CONCLUSION: In this population of healthy subjects and patients with
      hypertension, segmental bioimpedance was comparable to water displacement and
      ankle circumference and outperformed clinical assessment of pitting for the
      detection of ankle edema, supporting the use of segmental bioimpedance as a drug
      development tool to objectively quantify amlodipine-induced pedal edema.

PMID- 22385928
TI  - Efficacy of a commercial dentifrice containing 2% strontium chloride and 5%
      potassium nitrate for dentin hypersensitivity: a 3-day clinical study in adults
      in China.
AB  - BACKGROUND: Studies of dentifrices containing strontium chloride or potassium
      nitrate have documented the clinical efficacy of these formulations for dentin
      hypersensitivity (DH), but few studies have evaluated dentifrices containing both
      active ingredients. OBJECTIVE: The objective of this study was to compare the
      effects on DH of a dentifrice containing 2% strontium chloride and 5% potassium
      nitrate in a silica base (experimental dentifrice) with those of a dentifrice
      containing the same silica base without any active ingredient (control
      dentifrice). METHODS: Male and female patients aged 20 to 65 years with DH were
      eligible to participate in this randomized, double-blind, placebo-controlled
      study in China. Patients were assigned to receive the experimental or control
      dentifrice. At baseline, immediately after topical dentifrice use, and after 3
      days, patients received an oral examination of their hard and soft tissues,
      followed by an evaluation of DH that used the Yeaple Probe to measure tactile
      hypersensitivity and the Schiff Cold Air Scale to measure the perception of pain
      from an air blast stimulus. Adverse events (in particular, discomfort while
      brushing or alteration in taste) in the oral hard or soft tissues were monitored
      throughout the study. RESULTS: A total of 81 patients were enrolled (40 in the
      experimental group; 41 in the control group), of whom 79 (55 women; 24 men)
      completed the study. After topical use, the experimental group had a
      significantly higher mean (SD) tactile hypersensitivity score (19.47 [14.69] vs
      14.27 [5.76]; P = 0.047) and a significantly lower mean air blast
      hypersensitivity score (1.93 [0.51] vs 2.22 [0.60]; P = 0.026) than did the
      control group. After 3 days, the experimental group had a significantly higher
      mean tactile hypersensitivity score (19.87 [14.95] vs 14.51 [6.00]; P = 0.045)
      and a significantly lower air blast hypersensitivity score (1.80 [0.56] and 2.13
      [0.60]; P = 0.014) than the control group. After topical use and after 3 days,
      the experimental group had increases from baseline in tactile scores of 54.04%
      and 56.67%, respectively (both, P = 0.001) and reductions from baseline in air
      blast scores of 18.51% and 24.21% (both, P < 0.001); the control group had
      increases in tactile scores of 21.14% and 21.54% (P = 0.022 and P = 0.007) and
      reductions in air blast scores of 10.24% and 13.41% (P = 0.001 and P < 0.001). No
      adverse events were reported throughout the study. CONCLUSION: In these patients
      with DH in China, the dentifrice containing 2% strontium chloride and 5%
      potassium nitrate was efficacious in reducing DH when used instantly after
      topical dentifrice use and after 3 days of use.

PMID- 22385929
TI  - Plasma proteins take their toll on the joint in osteoarthritis.

PMID- 22385930
TI  - Hollow nitrogen-containing core/shell fibrous carbon nanomaterials as support to
      platinum nanocatalysts and their TEM tomography study.
AB  - Core/shell nanostructured carbon materials with carbon nanofiber (CNF) as the
      core and a nitrogen (N)-doped graphitic layer as the shell were synthesized by
      pyrolysis of CNF/polyaniline (CNF/PANI) composites prepared by in situ
      polymerization of aniline on CNFs. High-resolution transmission electron
      microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared and Raman
      analyses indicated that the PANI shell was carbonized at 900 degrees C. Platinum
      (Pt) nanoparticles were reduced by formic acid with catalyst supports. Compared
      to the untreated CNF/PANI composites, the carbonized composites were proven to be
      better supporting materials for the Pt nanocatalysts and showed superior
      performance as catalyst supports for methanol electrochemical oxidation. The
      current density of methanol oxidation on the catalyst with the core/shell
      nanostructured carbon materials is approximately seven times of that on the
      catalyst with CNF/PANI support. TEM tomography revealed that some Pt
      nanoparticles were embedded in the PANI shells of the CNF/PANI composites, which
      might decrease the electrocatalyst activity. TEM-energy dispersive spectroscopy
      mapping confirmed that the Pt nanoparticles in the inner tube of N-doped hollow
      CNFs could be accessed by the Nafion ionomer electrolyte, contributing to the
      catalytic oxidation of methanol.

PMID- 22385931
TI  - Effect of opioids on CXCL-8 production in healthy cats.
AB  - The aim of this study was to evaluate the effect of opioid exposure on CXC
      chemokine ligand (CXCL)-8 production in cats using whole blood culture. Morphine,
      buprenorphine, fentanyl, and saline control were administered intravenously to
      five cats and whole blood pathogen associated molecular pattern motif-induced
      CXCL-8 production capacity was evaluated. Morphine potentiated CXCL-8 production.
      To further characterize this effect of morphine, morphine was incubated with
      whole blood ex vivo and pathogen associated molecular pattern motif-induced CXCL
      8 production capacity was measured. There was a time and concentration dependent
      effect on CXCL-8 production, suggesting the proinflammatory effect of morphine is
      at least partially mediated by direct stimulatory effects on leukocytes.
      Additional investigation is indicated to assess the implications of the
      immunomodulatory actions of opioids in cats.

PMID- 22385932
TI  - Increased 2-hydroxylation of estrogen is associated with lower body fat and
      increased lean body mass in postmenopausal women.
AB  - Menopause is associated with changes in bone, muscle and fat mass. The importance
      of postmenopausal estrogen metabolism in bone health has been established.
      However, its relationship to body composition in postmenopausal women remains
      undetermined. The objective of this study is to determine the association between
      estrogen metabolism and body composition in postmenopausal women. This is a cross
      sectional study of 97 postmenopausal Caucasian women, 49-80 y.o., >=1 year from
      the last normal menstrual period or those who have had oophorectomy. Inactive [2
      hydroxyestrone (2OHE(1))] and active [16alpha-hydroxyestrone (16alpha-OHE(1))]
      urinary metabolites of estrogen were measured by ELISA. The whole and regional
      body composition was measured by DXA. We have found that both 2OHE(1), and
      2OHE(1)/16alpha-OHE(1) ratio were negatively correlated with % total fat, and %
      truncal fat but positively correlated with % total lean mass. Comparing the fat
      and lean parameters of body composition according to tertiles of 2OHE(1) and
      2OHE(1)/16alphaOHE(1) ratio showed that subjects in the lowest tertiles, had the
      highest % total fat, and % truncal fat and the lowest % total lean mass. Multiple
      regression analysis also showed 2OHE(1) and calcium intake as statistically
      significant predictors of all body composition parameters. In conclusion, in
      postmenopausal women, an increase in the metabolism of estrogen towards the
      inactive metabolites is associated with lower body fat and higher lean mass than
      those with predominance of the metabolism towards the active metabolites.

PMID- 22385933
TI  - A new look at renal dysfunction in the cirrhotic patient.
AB  - Hepatorenal syndrome (HRS) is a pre-renal azotemia-like acute renal failure
      occurring in patients with end-stage cirrhosis. HRS results from arteriolar
      vasodilatation, arteriolar underfilling, and intense renal vasoconstriction. By
      definition, it is not responsive to volume expansion, and the prognosis is
      especially poor even with the use of terlipressin or albumin dialysis or both. It
      may be difficult, on the basis of the current criteria, to clearly differentiate
      HRS from other causes of acute renal failure in cirrhosis. In addition, patients
      with HRS frequently have underlying chronic kidney changes that may not be
      reversible after transplantation. In the previous issue of Critical Care, a group
      of experts proposed a new classification of acute, acute-on-chronic, or chronic
      renal impairment in cirrhosis on the basis of the RIFLE (Risk, Injury, Failure,
      Loss, and End-stage kidney disease) criteria. The group proposed the term
      'hepatorenal disorder' to define patients with advanced cirrhosis and kidney
      dysfunction at an earlier stage, regardless of the mechanisms. As stated by the
      authors, more data are needed to clearly identify, by non-invasive means, those
      with a potential for improvement with liver transplantation and those who can
      undergo a combined liver and kidney transplantation.

PMID- 22385934
TI  - Vascular endothelial growth factor, as compared with placental growth factor, is
      increased in severe sepsis but not in organ failure.

PMID- 22385935
TI  - Heart failure: can you think of a better name?

PMID- 22385936
TI  - What's in a name?

PMID- 22385937
TI  - Cardiorenal rescue study in acute decompensated heart failure: rationale and
      design of CARRESS-HF, for the Heart Failure Clinical Research Network.
AB  - BACKGROUND: Worsening renal function is common among patients hospitalized for
      acute decompensated heart failure (ADHF). When this occurs, subsequent management
      decisions often pit the desire for effective decongestion against concerns about
      further worsening renal function. There are no evidence-based treatments or
      guidelines to assist in these difficult management decisions. Ultrafiltration is
      a potentially attractive alternative to loop diuretics for the management of
      fluid overload in patients with ADHF and worsening renal function. METHODS AND
      RESULTS: The National Heart, Lung, and Blood Institute Heart Failure Clinical
      Research Network designed a clinical trial to determine if ultrafiltration
      results in improved renal function and relief of congestion compared with stepped
      pharmacologic care when assessed 96 hours after randomization in patients with
      ADHF and cardiorenal syndrome. Enrollment began in June 2008. This paper
      describes the rationale and design of the Cardiorenal Rescue Study in Acute
      Decompensated Heart Failure (CARRESS-HF). CONCLUSIONS: Treating the signs and
      symptoms of congestion in ADHF is often complicated by worsening renal function.
      CARRESS-HF compares treatment strategies (ultrafiltration vs stepped
      pharmacologic care) for the management of worsening renal function in patients
      with ADHF. The results of the CARRESS-HF trial are expected to provide
      information and evidence as to the most appropriate approaches for treating this
      challenging patient population.

PMID- 22385939
TI  - Low serum total cholesterol level is a surrogate marker, but not a risk factor,
      for poor outcome in patients hospitalized with acute heart failure: a report from
      the Korean Heart Failure Registry.
AB  - BACKGROUND: Hypercholesterolemia is a major risk factor for incident coronary
      artery disease and the prevalence of heart failure (HF). The causal relationship
      between low total cholesterol (TC) levels and poor clinical outcome in patients
      with acute HF has not been investigated. This study evaluated the effect of
      cholesterol levels on the long-term outcome in patients hospitalized due to acute
      HF. METHODS AND RESULTS: We analyzed a cohort of 2,797 HF patients who were
      eligible for analysis in 3,200 patients of the Korean Heart Failure Registry.
      Patients were stratified into quartiles of TC (Q1 <133, Q2 133-158, Q3 159-190,
      and Q4 >190 mg/dL). Propensity score matching was performed with the patients in
      Q1 and Q4. Patients with lower serum TC had lower blood pressure, lower
      hemoglobin, lower serum sodium, and higher natriuretic peptide levels than
      patients with higher TC levels. Low TC was associated with increased risks for
      death and readmission due to HF; the adjusted hazard ratio (HR) of Q1 compared
      with Q4 was 1.57 (95% confidence interval [CI] 1.30-1.90). However, propensity
      score matching analysis revealed that low cholesterol itself did not affect
      outcome (HR 1.12, 95% CI 0.85-1.48). CONCLUSIONS: Low TC is strongly associated
      with mortality and morbidity in patients with HF. However, low TC seemed to be a
      secondary result of the patient's state rather than an independent risk factor
      for poor outcome.

PMID- 22385938
TI  - New insights into mechanisms of action of carvedilol treatment in chronic heart
      failure patients--a matter of time for contractility.
AB  - BACKGROUND: It is unclear whether improvement in left ventricular (LV) ejection
      fraction (LVEF) following treatment with a combined alpha(1),beta(1),beta(2)
      blockade can be attributed to improvement in LV contractility, to a reduction in
      afterload, and/or to improvements in LV remodeling and chamber size. We aimed to
      examine whether the observed improvement in LVEF following carvedilol treatment
      is due to changes in intrinsic myocardial contractility beyond changes in LV
      chamber size or loading conditions. METHODS AND RESULTS: In 49 consecutive
      patients with chronic heart failure (HF), LVEF <=35%, NYHA functional class II
      IV, on angiotensin-converting enzyme inhibitors but not on beta-blockers, LV
      contractile performance and remodeling were assessed by comprehensive
      echocardiography at baseline and after 3 and 6 months of treatment with
      carvedilol. Carvedilol treatment resulted in significant improvements in LVEF,
      shortening fraction, and velocity of circumferential shortening (VCF(c)). There
      were no significant changes in the mean arterial blood pressure or systemic
      vascular resistance index; but LV end-systolic wall stress (LVESS), effective
      arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end
      systolic dimensions and volumes were significantly reduced. Estimated end
      systolic elastance, VCF(c)-to-LVESS ratio, and pulsatile arterial compliance
      significantly improved after 6 months of treatment with carvedilol. The slope of
      the VCF(c) relationship to LVESS worsened from 0 to 3 months, but significantly
      improved from 3 to 6 months. CONCLUSIONS: Despite an initial transient negative
      inotropic effect from 0 to 3 months, carvedilol treatment was associated with a
      positive inotropic effect with significant improvement in load-independent
      indexes of myocardial contractility beyond what can be attributed to changes in
      LV chamber size and load after 3 months. There were no changes in systemic
      vascular resistance with carvedilol treatment; however, improvement in pulsatile
      arterial compliance and ventriculoarterial coupling suggested enhanced cardiac
      mechanoenergetic performance along with improved systemic arterial compliance.

PMID- 22385940
TI  - Association between prehospital delay and subsequent clinical course in patients
      with/hospitalized for heart failure.
AB  - BACKGROUND: The clinical consequences of prehospital delay in heart failure (HF)
      patients are unknown. This study explores the relationship between prehospital
      delay of HF patients and length of hospital stay, plasma values of brain
      natriuretic peptides (BNP) as well as the association of delay with all-cause
      mortality, readmission for HF, or all-cause readmissions during short- (60 days)
      and long-term (18 months) follow-up. METHODS: Data from 1023 hospitalized HF
      patients mean aged 71 years from the Coordinating study evaluating Outcomes of
      Advising and Counselling in HF study were analyzed. RESULTS: Patients who delayed
      less than 1 day had significantly shorter stay in hospital (10 days vs. 11 days,
      P = 0.033). They also had significantly (P = 0.004) lower median plasma values of
      BNP (377 pg/mL) at discharge compared to patients who delayed >24 hours (492
      pg/mL). Delay was not related to all-cause mortality and/or readmissions for HF.
      CONCLUSION: Although patients with a prehospital delay less than 1 day were more
      symptomatic on admission, they had a shorter hospital stay as well as lower
      plasma values of BNP at discharge. Delay was not associated hospital readmissions
      or mortality after discharge.

PMID- 22385941
TI  - Right ventricular longitudinal strain correlates well with right ventricular
      stroke work index in patients with advanced heart failure referred for heart
      transplantation.
AB  - BACKGROUND: Right ventricular (RV) systolic function has a critical role in
      determining the clinical outcome and success of using left ventricular assist
      devices (LVADs) in patients with refractory heart failure. Tissue Doppler and M
      mode measurements of tricuspid systolic motion (tricuspid S' and tricuspid
      annular plane systolic excursion [TAPSE]) are the most currently used methods for
      the quantification of RV longitudinal function; RV deformation analysis by
      speckle-tracking echocardiography (STE) has recently allowed the analysis of
      global RV longitudinal function. Using cardiac catheterization as the reference
      standard, this study aimed at exploring the correlation between RV longitudinal
      function by STE and RV stroke work index (RVSWI) in patients referred for cardiac
      transplantation. METHODS AND RESULTS: Right-side heart catheterization and
      transthoracic echo Doppler were simultaneously performed in 41 patients referred
      for cardiac transplantation evaluation for advanced systolic heart failure.
      Thermodilution RV stroke volume and invasive pulmonary pressures were used to
      obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging all
      segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall
      segments (free-wall RVLS). Tricuspid S' and TAPSE were also calculated. No
      significant correlations were found for TAPSE or tricuspid S' with RVSWI (r =
      0.14; r = 0.06; respectively). Close negative correlations between global RVLS
      and free-wall RVLS with the RVSWI were found (r = -0.75; r = -0.82; respectively;
      both P < .0001). Furthermore, free-wall RVLS demonstrated the highest diagnostic
      accuracy (area under the receiver operating characteristic (ROC) curve 0.90) and
      good sensitivity and specificity of 92% and 86%, respectively, to predict
      depressed RVSWI using a cutoff value of less than -11.8%. CONCLUSIONS: In a group
      of patients referred for heart transplantation, TAPSE and tricuspid S' did not
      correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by
      STE correlated well with RVSWI, providing a better estimation of RV systolic
      performance.

PMID- 22385942
TI  - Prevalence of, associations with, and prognostic value of tricuspid annular plane
      systolic excursion (TAPSE) among out-patients referred for the evaluation of
      heart failure.
AB  - BACKGROUND: Prevalence, predictors, and prognostic value of right ventricular
      (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE)
      in patients with chronic heart failure (CHF) symptoms with a broad range of left
      ventricular ejection fraction (LVEF) are unknown. METHODS AND RESULTS: Of 1,547
      patients, mean (+/-SD) age was 71 +/- 11 years, 48% were women, median
      (interquartile range [IQR]) TAPSE was 18.5 (14.0-22.7) mm, mean LVEF was 47 +/-
      16%, 47% had LVEF <=45% and 67% were diagnosed with CHF, defined as systolic (S
      HF) if LVEF was <=45% and as heart failure with preserved ejection fraction
      (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR)
      follow-up of 63 (41-75) months, mortality was 34%. In multivariable analysis,
      increasing age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York
      Heart Association functional class, right atrial volume index, and transtricuspid
      pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and
      atrial fibrillation (AF) or COPD were associated with an adverse prognosis.
      Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as
      the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a
      TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT
      proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction.
      CONCLUSIONS: In patients with CHF, low values for TAPSE are common, especially in
      those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of
      outcome.

PMID- 22385943
TI  - Differentiation of cardiac and noncardiac dyspnea using bioelectrical impedance
      vector analysis (BIVA).
AB  - BACKGROUND: There is no gold standard for the differential diagnosis of acute
      dyspnea despite the usefulness of N-terminal pro-B-type natriuretic peptide (NT
      proBNP) and lung ultrasound. No study has evaluated the contribution of
      bioelectrical impedance vector analysis (BIVA) in discriminating between cardiac
      and noncardiac dyspnea. We sought to determine whether a relationship exists
      between ultrasound detection of lung congestion, NT-proBNP, and BIVA in patients
      with acute dyspnea. METHODS AND RESULTS: Eligible patients were between 50 and 95
      years, with an estimated glomerular filtration rate of >=30 mL min(-1) 1.73 m(
      2), who presented to an emergency department with dyspnea. Dyspnea was classified
      by reviewers blinded to BIVA as cardiac or noncardiac based on physical
      examination, electrocardiogram, chest X-ray, NT-proBNP, and B-lines of lung
      congestion on ultrasound. Overall, 315 patients were enrolled (median age 77
      years, 48% male). An adjudicated diagnosis of cardiac dyspnea was established in
      169 (54%). Using BIVA, vector positions below -1 SD of the Z-score of reactance
      were associated with peripheral congestion (chi(2) = 115; P < .001). BIVA
      measures were reasonably accurate in discriminating cardiac and noncardiac
      dyspnea (69% sensitivity, 79% specificity, 80% area under the receiver operating
      characteristic curve). CONCLUSIONS: In patients presenting with acute dyspnea,
      the combination of BIVA and lung ultrasound may provide a rapid noninvasive
      method to determine the cause of dyspnea.

PMID- 22385944
TI  - Beta-blockers and weight change in patients with chronic heart failure.
AB  - BACKGROUND: There is an inverse association between body mass and mortality in
      patients with chronic heart failure (CHF). Beta-blockers have been associated
      with weight gain. We wanted to examine the relation between beta-blocker use and
      weight in a population of patients with CHF. METHODS AND RESULTS: We weighed 276
      patients presenting with CHF (mean age 71.3 +/- 9.5 years, 72.8% male). None were
      taking a beta-blocker at presentation, but all had started by 4 months' follow
      up. The patients were reweighed after 1 year. There was an increase in weight
      (0.9 +/- 7.0 kg; P = .03) and body mass index (0.2 +/- 2.4 kg/m(2); P = .02).
      Patients in New York Heart Association (NYHA) functional class III or IV had no
      significant weight change, whereas those in class I or II had an increase of 1.62
      kg (P < .0001). In patients who had no peripheral edema at baseline or 1 year,
      there was a greater increase in weight (1.3 +/- 6.9 kg; P = .01). CONCLUSIONS:
      Beta-blocker use and intensification of heart failure treatment is associated
      with weight gain in CHF. The increase is greater in those who are nonedematous
      and tends to occur in patients with NYHA functional class I and II symptoms.

PMID- 22385945
TI  - A positive 2-item Patient Health Questionnaire depression screen among
      hospitalized heart failure patients is associated with elevated 12-month
      mortality.
AB  - BACKGROUND: Given the association of depression with poorer cardiac outcomes, an
      American Heart Association Science Advisory has advocated routine screening of
      cardiac patients for depression using the 2-item Patient Health Questionnaire
      (PHQ-2) "at a minimum." However, the prognostic value of the PHQ-2 among HF
      patients is unknown. METHODS AND RESULTS: We screened hospitalized HF patients
      (ejection fraction [EF] <40%) that staff suspected may be depressed with the PHQ
      2, and then determined vital status at up to 12-months follow-up. At baseline,
      PHQ-2 depression screen-positive patients (PHQ-2+; n = 371), compared with PHQ-2
      screen-negative patients (PHQ-2-; n = 100), were younger (65 vs 70 years) and
      more likely to report New York Heart Association (NYHA) functional class III/IV
      than class II symptoms (67% vs. 39%) and lower levels of physical and mental
      health-related quality of life (all P <= .002); they were similar in other
      characteristics (65% male, 26% mean EF). At 12 months, 20% of PHQ-2+ versus 8% of
      PHQ-2- patients had died (P = .007) and PHQ-2 status remained associated with
      both all-cause (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.4-6.7; P =
      .003) and cardiovascular (HR 2.7, 95% CI 1.1-6.6; P = .03) mortality even after
      adjustment for age, gender, EF, NYHA functional class, and a variety of other
      covariates. CONCLUSIONS: Among hospitalized HF patients, a positive PHQ-2
      depression screen is associated with an elevated 12-month mortality risk.

PMID- 22385946
TI  - Depression predicts repeated heart failure hospitalizations.
AB  - OBJECTIVE: Management of depression, if it is independently associated with
      repeated hospitalizations for heart failure (HF), offers promise as a viable and
      cost-effective strategy to improve health outcomes and reduce health care costs
      for HF. The objective of this study was to assess the association between
      depression and the number of HF-related hospitalizations in patients with low-to
      moderate systolic or diastolic dysfunction, after controlling for illness
      severity, socioeconomic factors, physician adherence to evidence-based
      medications, patient adherence to HF drug therapy, and patient adherence to salt
      restrictions. METHODS AND RESULTS: The Heart Failure Adherence and Retention
      Trial (HART) was a randomized behavioral trial to evaluate whether patient self
      management skills coupled with HF education improved patient outcomes. Depression
      was measured at baseline with the Geriatric Depression Scale (GDS). The number of
      hospitalizations was analyzed with a negative binomial regression model that
      included an offset term to account for the differential duration of follow-up for
      individual subjects. The average unadjusted number of hospitalizations per year
      was 0.40 in the depressed group (GDS >=10) and 0.33 in the nondepressed group
      (GDS <10). Depression was a strong predictor (incident rate ratio 1.45; P = .006)
      after adjusting for physician adherence to evidence-based medication use, patient
      adherence to HF drug therapy, patient adherence to salt restriction, illness
      severity, HF severity (6-minute walk <620 feet), and socioeconomic factors.
      CONCLUSIONS: Depression is a strong psychosocial predictor of repeated
      hospitalizations for HF. Compared with nondepressed individuals, those with
      depression were hospitalized for HF 1.45 times more often, even after controlling
      for physician adherence to evidence-based medications and patient adherence to HF
      drug therapy and salt restrictions. This finding suggests that clinicians should
      screen for depression early in the course of HF management.

PMID- 22385947
TI  - Serum glutathione S-transferase P1 1 in prediction of cardiac function.
AB  - BACKGROUND: Glutathione S-transferase P1 1 (GSTP1) belongs to the multigene
      isozyme family involved in cellular response to oxidative stress and apoptosis.
      Our initial retrospective proteomic analysis suggested that GSTP1 is associated
      with heart failure (HF). Although pro-B-type natriuretic peptide (proBNP) serves
      currently as a surrogate diagnostic and prognostic parameter in HF patients, its
      specificity remains uncertain. We hypothesized that GSTP1 might be a useful serum
      marker in the monitoring of HF patients. METHODS AND RESULTS: Serum GSTP1 and
      proBNP were prospectively measured in 193 patients subdivided based on their
      ejection fraction (EF) either in equal-sized quintiles or predefined EF groups
      >52%, 43%-52%, 33%-42%, 23%-32% and <=22%. At a cutoff of >=231 ng/mL, GSTP1
      identified HF patients with EF <=22% with 81% sensitivity and 83% specificity,
      and at a cutoff of >=655 pg/mL, proBNP identified the same patient group with 84%
      sensitivity and 22% specificity. GSTP1 at a >=126 ng/mL cutoff identified EF
      <=42% with 90% sensitivity and 95% specificity, or proBNP at a >=396 pg/mL cutoff
      had 97% sensitivity and 20% specificity. In regression analyses, GSTP1, but not
      proBNP, discriminated between EF <=42% and EF >42% in HF patients. CONCLUSIONS:
      These results suggest that GSTP1 is strongly associated with HF and could serve
      as a sensitive and specific marker to predict the ventricular function in HF
      patients.

PMID- 22385949
TI  - Sudden cardiac death is still a risk for some peripartum cardiomyopathy mothers.

PMID- 22385950
TI  - Estimation of systolic pulmonary pressure and right ventricular systolic
      impairment.

PMID- 22385952
TI  - The unfolding story of a redox chaperone.
AB  - Oxidative stress, especially in combination with heat stress, poses a life
      threatening challenge to many organisms by causing protein misfolding and
      aggregation. In this issue, Reichmann et al. demonstrate how a destabilized
      linker region of the bacterial chaperone Hsp33 prevents aggregation of a
      denatured protein by stabilizing structural elements.

PMID- 22385953
TI  - Greasing the path to BAX/BAK activation.
AB  - BAX/BAK activation leading to mitochondrial outer-membrane permeabilization is a
      key commitment point in apoptosis. Chipuk et al. now identify two sphingolipids
      as specific cofactors for BAX/BAK activation that lower the threshold for
      apoptosis-associated cytochrome c release. Association of mitochondria with other
      cellular membrane compartments is required for BAK/BAX exposure to these
      sphingolipids.

PMID- 22385954
TI  - DNA-damage-induced differentiation in hematopoietic stem cells.
AB  - Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional
      potential. Wang et al. now provide evidence for an HSC-specific differentiation
      checkpoint mediated by the transcription factor BATF, which limits self-renewal
      of HSCs in response to the accumulation of DNA damage.

PMID- 22385955
TI  - Synaptic vesicle distribution by conveyor belt.
AB  - The equal distribution of synaptic vesicles among synapses along the axon is
      critical for robust neurotransmission. Wong et al. show that the continuous
      circulation of synaptic vesicles throughout the axon driven by molecular motors
      ultimately yields this even distribution.

PMID- 22385957
TI  - Single-cell exome sequencing and monoclonal evolution of a JAK2-negative
      myeloproliferative neoplasm.
AB  - Tumor heterogeneity presents a challenge for inferring clonal evolution and
      driver gene identification. Here, we describe a method for analyzing the cancer
      genome at a single-cell nucleotide level. To perform our analyses, we first
      devised and validated a high-throughput whole-genome single-cell sequencing
      method using two lymphoblastoid cell line single cells. We then carried out whole
      exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative
      neoplasm patient. The sequencing data from 58 cells passed our quality control
      criteria, and these data indicated that this neoplasm represented a monoclonal
      evolution. We further identified essential thrombocythemia (ET)-related candidate
      mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression.
      This pilot study allowed the initial characterization of the disease-related
      genetic architecture at the single-cell nucleotide level. Further, we established
      a single-cell sequencing method that opens the way for detailed analyses of a
      variety of tumor types, including those with high genetic complex between
      patients.

PMID- 22385956
TI  - Mechanisms for insulin resistance: common threads and missing links.
AB  - Insulin resistance is a complex metabolic disorder that defies explanation by a
      single etiological pathway. Accumulation of ectopic lipid metabolites, activation
      of the unfolded protein response (UPR) pathway, and innate immune pathways have
      all been implicated in the pathogenesis of insulin resistance. However, these
      pathways are also closely linked to changes in fatty acid uptake, lipogenesis,
      and energy expenditure that can impact ectopic lipid deposition. Ultimately,
      these cellular changes may converge to promote the accumulation of specific lipid
      metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a
      common final pathway leading to impaired insulin signaling and insulin
      resistance.

PMID- 22385958
TI  - Single-cell exome sequencing reveals single-nucleotide mutation characteristics
      of a kidney tumor.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has
      very few mutations that are shared between different patients. To better
      understand the intratumoral genetics underlying mutations of ccRCC, we carried
      out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue.
      Our data indicate that this tumor was unlikely to have resulted from mutations in
      VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor
      did not contain any significant clonal subpopulations and also showed that
      mutations that had different allele frequencies within the population also had
      different mutation spectrums. Analyses of these data allowed us to delineate a
      detailed intratumoral genetic landscape at a single-cell level. Our pilot study
      demonstrates that ccRCC may be more genetically complex than previously thought
      and provides information that can lead to new ways to investigate individual
      tumors, with the aim of developing more effective cellular targeted therapies.

PMID- 22385959
TI  - Dual regulation of miRNA biogenesis generates target specificity in neurotrophin
      induced protein synthesis.
AB  - Control of translation is a fundamental source of regulation in gene expression.
      The induction of protein synthesis by brain-derived neurotrophic factor (BDNF)
      critically contributes to enduring modifications of synaptic function, but how
      BDNF selectively affects only a minority of expressed mRNAs is poorly understood.
      We report that BDNF rapidly elevates Dicer, increasing mature miRNA levels and
      inducing RNA processing bodies in neurons. BDNF also rapidly induces Lin28,
      causing selective loss of Lin28-regulated miRNAs and a corresponding upregulation
      in translation of their target mRNAs. Binding sites for Lin28-regulated miRNAs
      are necessary and sufficient to confer BDNF responsiveness to a transcript. Lin28
      deficiency, or expression of a Lin28-resistant Let-7 precursor miRNA, inhibits
      BDNF translation specificity and BDNF-dependent dendrite arborization. Our data
      establish that specificity in BDNF-regulated translation depends upon a two-part
      posttranscriptional control of miRNA biogenesis that generally enhances mRNA
      repression in association with GW182 while selectively derepressing and
      increasing translation of specific mRNAs.

PMID- 22385960
TI  - Order out of disorder: working cycle of an intrinsically unfolded chaperone.
AB  - The redox-regulated chaperone Hsp33 protects organisms against oxidative stress
      that leads to protein unfolding. Activation of Hsp33 is triggered by the
      oxidative unfolding of its own redox-sensor domain, making Hsp33 a member of a
      recently discovered class of chaperones that require partial unfolding for full
      chaperone activity. Here we address the long-standing question of how chaperones
      recognize client proteins. We show that Hsp33 uses its own intrinsically
      disordered regions to discriminate between unfolded and partially structured
      folding intermediates. Binding to secondary structure elements in client proteins
      stabilizes Hsp33's intrinsically disordered regions, and this stabilization
      appears to mediate Hsp33's high affinity for structured folding intermediates.
      Return to nonstress conditions reduces Hsp33's disulfide bonds, which then
      significantly destabilizes the bound client proteins and in doing so converts
      them into less-structured, folding-competent client proteins of ATP-dependent
      foldases. We propose a model in which energy-independent chaperones use internal
      order-to-disorder transitions to control substrate binding and release.

PMID- 22385961
TI  - Spindle pole bodies exploit the mitotic exit network in metaphase to drive their
      age-dependent segregation.
AB  - Like many asymmetrically dividing cells, budding yeast segregates mitotic spindle
      poles nonrandomly between mother and daughter cells. During metaphase, the
      spindle positioning protein Kar9 accumulates asymmetrically, localizing
      specifically to astral microtubules emanating from the old spindle pole body
      (SPB) and driving its segregation to the bud. Here, we show that the SPB
      component Nud1/centriolin acts through the mitotic exit network (MEN) to specify
      asymmetric SPB inheritance. In the absence of MEN signaling, Kar9 asymmetry is
      unstable and its preference for the old SPB is disrupted. Consistent with this,
      phosphorylation of Kar9 by the MEN kinases Dbf2 and Dbf20 is not required to
      break Kar9 symmetry but is instead required to maintain stable association of
      Kar9 with the old SPB throughout metaphase. We propose that MEN signaling links
      Kar9 regulation to SPB identity through biasing and stabilizing the age
      insensitive, cyclin-B-dependent mechanism of symmetry breaking.

PMID- 22385962
TI  - Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but
      is dispensable for chemotaxis.
AB  - Lamellipodia are sheet-like, leading edge protrusions in firmly adherent cells
      that contain Arp2/3-generated dendritic actin networks. Although lamellipodia are
      widely believed to be critical for directional cell motility, this notion has not
      been rigorously tested. Using fibroblasts derived from Ink4a/Arf-deficient mice,
      we generated a stable line depleted of Arp2/3 complex that lacks lamellipodia.
      This line shows defective random cell motility and relies on a filopodia-based
      protrusion system. Utilizing a microfluidic gradient generation system, we tested
      the role of Arp2/3 complex and lamellipodia in directional cell migration.
      Surprisingly, Arp2/3-depleted cells respond normally to shallow gradients of
      PDGF, indicating that lamellipodia are not required for fibroblast chemotaxis.
      Conversely, these cells cannot respond to a surface-bound gradient of
      extracellular matrix (haptotaxis). Consistent with this finding, cells depleted
      of Arp2/3 fail to globally align focal adhesions, suggesting that one principle
      function of lamellipodia is to organize cell-matrix adhesions in a spatially
      coherent manner.

PMID- 22385963
TI  - Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial
      pathway of apoptosis.
AB  - Mitochondria are functionally and physically associated with heterotypic
      membranes, yet little is known about how these interactions impact mitochondrial
      outer-membrane permeabilization (MOMP) and apoptosis. We observed that
      dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX
      dependent cytochrome c (cyto c) release. Biochemical purification of neutral
      sphingomyelinases that correlated with MOMP sensitization suggested that
      sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and
      enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the
      sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP
      from heavy membrane preparations but failed to influence MOMP in the presence of
      sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid
      products, sphingosine-1-PO(4) and hexadecenal, cooperated specifically with BAK
      and BAX, respectively. Sphingolipid metabolism was also required for cellular
      responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis
      are coordinated through BH3-only proteins and a specific lipid milieu that is
      maintained by heterotypic membrane-mitochondrial interactions.

PMID- 22385964
TI  - A differentiation checkpoint limits hematopoietic stem cell self-renewal in
      response to DNA damage.
AB  - Checkpoints that limit stem cell self-renewal in response to DNA damage can
      contribute to cancer protection but may also promote tissue aging. Molecular
      components that control stem cell responses to DNA damage remain to be
      delineated. Using in vivo RNAi screens, we identified basic leucine zipper
      transcription factor, ATF-like (BATF) as a major component limiting self-renewal
      of hematopoietic stem cells (HSCs) in response to telomere dysfunction and gamma
      irradiation. DNA damage induces BATF in a G-CSF/STAT3-dependent manner resulting
      in lymphoid differentiation of HSCs. BATF deletion improves HSC self-renewal and
      function in response to gamma-irradiation or telomere shortening but results in
      accumulation of DNA damage in HSCs. Analysis of bone marrow from patients with
      myelodysplastic syndrome supports the conclusion that DNA damage-dependent
      induction of BATF is conserved in human HSCs. Together, these results provide
      experimental evidence that a BATF-dependent differentiation checkpoint limits
      self-renewal of HSCs in response to DNA damage.

PMID- 22385965
TI  - Slug and Sox9 cooperatively determine the mammary stem cell state.
AB  - Regulatory networks orchestrated by key transcription factors (TFs) have been
      proposed to play a central role in the determination of stem cell states.
      However, the master transcriptional regulators of adult stem cells are poorly
      understood. We have identified two TFs, Slug and Sox9, that act cooperatively to
      determine the mammary stem cell (MaSC) state. Inhibition of either Slug or Sox9
      blocks MaSC activity in primary mammary epithelial cells. Conversely, transient
      coexpression of exogenous Slug and Sox9 suffices to convert differentiated
      luminal cells into MaSCs with long-term mammary gland-reconstituting ability.
      Slug and Sox9 induce MaSCs by activating distinct autoregulatory gene expression
      programs. We also show that coexpression of Slug and Sox9 promotes the
      tumorigenic and metastasis-seeding abilities of human breast cancer cells and is
      associated with poor patient survival, providing direct evidence that human
      breast cancer stem cells are controlled by key regulators similar to those
      operating in normal murine MaSCs.

PMID- 22385966
TI  - Neuropeptide delivery to synapses by long-range vesicle circulation and sporadic
      capture.
AB  - Neurotransmission requires anterograde axonal transport of dense core vesicles
      (DCVs) containing neuropeptides and active zone components from the soma to nerve
      terminals. However, it is puzzling how one-way traffic could uniformly supply
      sequential release sites called en passant boutons. Here, Drosophila neuropeptide
      containing DCVs are tracked in vivo for minutes with a new method called
      simultaneous photobleaching and imaging (SPAIM). Surprisingly, anterograde DCVs
      typically bypass proximal boutons to accumulate initially in the most distal
      bouton. Then, excess distal DCVs undergo dynactin-dependent retrograde transport
      back through proximal boutons into the axon. Just before re-entering the soma,
      DCVs again reverse for another round of anterograde axonal transport. While
      circulating over long distances, both anterograde and retrograde DCVs are
      captured sporadically in en passant boutons. Therefore, vesicle circulation,
      which includes long-range retrograde transport and inefficient bidirectional
      capture, overcomes the limitations of one-way anterograde transport to uniformly
      supply release sites with DCVs.

PMID- 22385967
TI  - Acute cannabinoids impair working memory through astroglial CB1 receptor
      modulation of hippocampal LTD.
AB  - Impairment of working memory is one of the most important deleterious effects of
      marijuana intoxication in humans, but its underlying mechanisms are presently
      unknown. Here, we demonstrate that the impairment of spatial working memory (SWM)
      and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3
      CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully
      abolished in conditional mutant mice lacking type-1 cannabinoid receptors
      (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in
      glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D
      aspartate receptors (NMDAR) and of synaptic trafficking of glutamate alpha-amino
      3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes
      cannabinoid effects on SWM and LTD induction and expression. We conclude that the
      impairment of working memory by marijuana and cannabinoids is due to the
      activation of astroglial CB(1)R and is associated with astroglia-dependent
      hippocampal LTD in vivo.

PMID- 22385969
TI  - SnapShot: Chromosome confirmation capture.

PMID- 22385968
TI  - Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and
      risk for schizophrenia.
AB  - How extrinsic stimuli and intrinsic factors interact to regulate continuous
      neurogenesis in the postnatal mammalian brain is unknown. Here we show that
      regulation of dendritic development of newborn neurons by Disrupted-in
      Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires
      neurotransmitter GABA-induced, NKCC1-dependent depolarization through a
      convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early
      postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization
      to hyperpolarization is accelerated. Extending the period of GABA-induced
      depolarization or maternal deprivation stress restores DISC1-dependent dendritic
      regulation through mTOR pathway during early-postnatal hippocampal neurogenesis.
      Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for
      schizophrenia in two independent case control studies. Our study uncovers an
      interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia
      susceptibility pathways, in controlling neurogenesis and suggests critical roles
      of developmental tempo and experience in manifesting the impact of susceptibility
      genes on neuronal development and risk for mental disorders.

PMID- 22385970
TI  - Graft dislocation and hypotony after Descemet's stripping automated endothelial
      keratoplasty in patients with previous glaucoma surgery.
AB  - PURPOSE: To determine if patients with prior glaucoma surgery experience higher
      rates of postoperative graft dislocation after Descemet's stripping automated
      endothelial keratoplasty (DSAEK) and to determine if postoperative hypotony may
      be a risk factor in these patients. DESIGN: Retrospective, comparative analysis
      of an interventional case series. PARTICIPANTS: Eight hundred fifty-four eyes (67
      eyes with prior glaucoma surgery and 787 controls) from 582 patients who
      underwent DSAEK at 1 institution between January 2005 and April 2011. METHODS:
      Groups were compared with regard to preoperative, intraoperative, and
      postoperative parameters. Continuous variables were compared using the
      independent samples t test or Mann-Whitney U test. Categorical variables were
      compared using the chi-square test or Fisher exact test. MAIN OUTCOME MEASURES:
      Frequencies of postoperative graft dislocation and postoperative hypotony.
      RESULTS: Study eyes before surgery differed from control eyes with regard to
      corneal thickness (768 vs. 655 MUm; P<0.001) and intraocular pressure (13 vs. 16
      mmHg; P<0.001). Postoperative graft dislocation occurred significantly more
      frequently in study eyes compared with control eyes (9% vs. 2%; P = 0.008). Among
      eyes in which dislocation occurred, postoperative hypotony was present in 5 study
      eyes (83%) and 0 control eyes. CONCLUSIONS: Previous glaucoma surgery was
      associated with a significantly increased rate of graft dislocation compared with
      control eyes. Dislocation was related strongly to postoperative hypotony in eyes
      with prior glaucoma surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 22385971
TI  - Improving the second-eye refractive error in patients undergoing bilateral
      sequential cataract surgery.
AB  - PURPOSE: To assess the refractive error in the second eye to undergo surgery when
      the intraocular lens (IOL) power was modified to correct 50% of the error from
      the first eye when such an error exceeded 0.50 diopter (D). DESIGN: Prospective,
      observational case series. PARTICIPANTS: Two hundred fifty patients with
      bilateral, sequential cataract surgery. METHODS: Two hundred fifty consecutive
      patients who underwent the first-eye cataract operation 1 to 3 months earlier
      were scheduled for cataract surgery in the second eye. When choosing the IOL
      power for the second eye, the calculations were adjusted to correct 50% of the
      first-eye refractive error (FERE). The adjusted second-eye refractive error
      (aSERE) was evaluated 6 to 8 weeks after surgery. It was compared with the FERE,
      with a potential nonadjusted SERE, and with a potential fully adjusted SERE. MAIN
      OUTCOME MEASURES: Postoperative refractive error. RESULTS: The median aSERE was
      significantly lower in the second eye compared with the median FERE in the 47
      cases in which the FERE ranged from -0.50 to -1.00 D (-0.12 vs. -0.66 D), in the
      15 cases in which the FERE exceeded -1.00 D (-0.12 vs. -1.25 D), in the 24 cases
      in which the FERE ranged from 0.50 to 1.00 D (-0.03 vs. 0.65 D), and in the 11
      cases in which the FERE exceeded 1.00 D (-0.29 vs. 1.19 D). The difference was
      statistically significant in all categories (P<0.00001). CONCLUSIONS: In patients
      undergoing bilateral sequential cataract surgery and in cases in which the FERE
      exceeded 0.50 D, the refractive error of the second eye can be improved by
      modifying the IOL power to correct up to 50% of the error from the first eye.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 22385972
TI  - [Non-fortuitous dynamin II mutation-related association: neutropenia and Charcot
      Marie-Tooth disease].
AB  - Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a
      genetically and clinically heterogeneous group of disorders of the peripheral
      nervous system. Mutations in multiple genes are currently known. We report an
      original case of CMT associated with chronic neutropenia in a patient with a
      K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with
      alterated cognitive function. Associated manifestations may guide molecular
      study.

PMID- 22385973
TI  - [Cerebral venous thrombosis during acute herpes simplex menigoradicultis. What is
      the pathophysiological mechanism?].

PMID- 22385974
TI  - [Address from the president, January 13, 2012].

PMID- 22385975
TI  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leucoencephalopathy (CADASIL) revealed by Claude's syndrome.

PMID- 22385976
TI  - PhiSiGns: an online tool to identify signature genes in phages and design PCR
      primers for examining phage diversity.
AB  - BACKGROUND: Phages (viruses that infect bacteria) have gained significant
      attention because of their abundance, diversity and important ecological roles.
      However, the lack of a universal gene shared by all phages presents a challenge
      for phage identification and characterization, especially in environmental
      samples where it is difficult to culture phage-host systems. Homologous conserved
      genes (or "signature genes") present in groups of closely-related phages can be
      used to explore phage diversity and define evolutionary relationships amongst
      these phages. Bioinformatic approaches are needed to identify candidate signature
      genes and design PCR primers to amplify those genes from environmental samples;
      however, there is currently no existing computational tool that biologists can
      use for this purpose. RESULTS: Here we present PhiSiGns, a web-based and
      standalone application that performs a pairwise comparison of each gene present
      in user-selected phage genomes, identifies signature genes, generates alignments
      of these genes, and designs potential PCR primer pairs. PhiSiGns is available at
      (http://www.phantome.org/phisigns/; http://phisigns.sourceforge.net/) with a link
      to the source code. Here we describe the specifications of PhiSiGns and
      demonstrate its application with a case study. CONCLUSIONS: PhiSiGns provides
      phage biologists with a user-friendly tool to identify signature genes and design
      PCR primers to amplify related genes from uncultured phages in environmental
      samples. This bioinformatics tool will facilitate the development of novel
      signature genes for use as molecular markers in studies of phage diversity,
      phylogeny, and evolution.

PMID- 22385977
TI  - No systemic reactions to influenza vaccination in egg-sensitized tertiary-care
      pediatric patients.
AB  - BACKGROUND: There are numerous, disparate guidelines for influenza vaccination in
      egg-allergic patients. We aimed to describe the outcome of selectively applied
      guidelines, based on risk-stratification, to our high risk, egg-allergic,
      tertiary-care pediatric population. METHODS: Egg allergy was confirmed with skin
      testing. The vaccine administered was an adjuvunated 2009 H1N1 influenza A
      vaccine with < 0.165 mcg/ml ovalbumin. Patients with mild egg allergy were to
      receive the vaccination in 1 dose, those with severe egg allergy were to receive
      2 split doses, and patients with exquisite egg allergy or significant co
      morbidities were to be skin tested with the vaccine (prick full strength,
      intradermal 1:100 of final concentration without adjuvant) and had 5 step
      desensitization if the testing was positive, or 1-2 step administration if
      negative. Patients were observed for 60 minutes after the final dose and
      anaphylaxis treatment was available. We report the frequency of allergic
      reactions. RESULTS: Ninety-nine patients were referred and 79 had positive egg
      testing. Asthma was present in 67% and 30% had prior anaphylaxis to egg. We
      vaccinated 77 of 79 patients: 71 without performing vaccine skin testing. Two
      refused vaccination. No patient had a systemic reaction or required treatment.
      Two patients experienced positive testing to the adjuvanated intradermal vaccine,
      but were negative without adjuvant. CONCLUSIONS: Our results suggest that most
      egg-allergic tertiary care pediatric patients can be vaccinated with a low
      ovalbumin content influenza vaccine without prior vaccine testing. Vaccine skin
      testing, if used at all, can be reserved for special circumstances. The squalene
      adjuvant may cause an irritant reaction with intradermal testing.

PMID- 22385978
TI  - A model of developmental evolution: selection, pleiotropy and compensation.
AB  - Development and physiology translate genetic variation into phenotypic variation
      and determine the genotype-phenotype map, such as which gene affects which
      character (pleiotropy). Any genetic change in this mapping reflects a change in
      development. Here, we discuss evidence for variation in pleiotropy and propose
      the selection, pleiotropy and compensation model (SPC) for adaptive evolution. It
      predicts that adaptive change in one character is associated with deleterious
      pleiotropy in others and subsequent selection to compensate for these pleiotropic
      effects. The SPC model provides a unifying perspective for a variety of puzzling
      phenomena, including developmental systems drift and character homogenization.
      The model suggests that most adaptive signatures detected in genome scans could
      be the result of compensatory changes, rather than of progressive character
      adaptations.

PMID- 22385979
TI  - A new approach for rapid and reliable enumeration of circulating endothelial
      cells in patients.
AB  - BACKGROUND: Mature circulating endothelial cells (CECs) are surrogate markers of
      endothelial damage/dysfunction. A lack of standardized assays and consensus on
      CEC phenotype has resulted in a wide variation of reported CEC numbers (4-1300
      per mL). OBJECTIVES: Given the need for a quick, reliable, robust and validated
      CEC assay at an affordable price, we present a novel approach to enumerate CECs
      using a multi-parameter flow cytometric (FCM) method without immunological pre
      enrichment. METHODS: CECs were defined as CD34+, CD45neg, CD146+ and DNA+ events
      based on the immunophenotype of endothelial cells from vein-wall dissections. As
      CECs express high levels of CD34, we based our assay on absolute CD34 counts
      after analyzing all CD34 positive events in a total blood volume of 4 mL needed
      for a precise enumeration of CECs at a frequency of < 1 cell MUL(-1). RESULTS:
      The endothelial origin of CECs was confirmed by morphology, immunohistochemistry
      and gene expression. The new FCM assay was tested in parallel with a validated
      assay (i.e. CellSearch). CEC levels ranged from 4 to 79 CEC mL(-1) in healthy
      individuals and were significantly higher in patients with advanced solid
      malignancies (P = 0.0008) and in patients with hematological malignancies (P <
      0.0001). CONCLUSIONS: This flow cytometric method should be useful as a fast and
      economical assay to enumerate and characterize CECs.

PMID- 22385981
TI  - Ajmaline Test and ESC 2010 clinical practice guidelines on atrial fibrillation.

PMID- 22385983
TI  - Nutritional status, heart failure and minimum basic data set.

PMID- 22385984
TI  - Electrocardiographic abnormalities improve classification of coronary heart
      disease risk in women: Tehran Lipid and Glucose Study.
AB  - OBJECTIVES: To examine the added value of electrocardiogram (ECG) abnormalities
      beyond the Framingham risk score (FRS) in risk stratification for coronary heart
      disease (CHD) in a population of Middle Eastern women. METHODS: The study
      population consisted of 2568 women aged >=30 years, free from CHD symptoms and
      with no major Q or QS wave or complete left-bundle branch block in their baseline
      ECG. ECG abnormalities included ST depression (Minnesota codes 4.1-4.2), or T
      wave items (Minnesota codes 5.1-5.2). Participants were categorized into 3
      groups, according to their FRS. Cox regression analysis was used to estimate the
      hazard ratios (HR) of CHD events for ECG abnormalities among each FRS group. Net
      Reclassification Index (NRI) was used as the measure of predictive ability added
      to the FRS by ECG abnormalities. RESULTS: During 9.3 years, 127 CHD events
      occurred. In the FRS adjusted analysis, the HRs (95%CI) of CHD events were 3.69
      (0.87-15.68), 3.82 (2.01-7.23) and 1.39 (0.47-4.16) for ECG abnormalities in each
      FRS category (i.e. 0-4.9%, 5-19.9 and >=20%, respectively). Addition of ECG
      abnormalities to FRS did not significantly increase the C-statistics (0.838), but
      improved the predictive ability of the FRS by 20.8 (95% CIs 5.0-38.9) using the
      cut point free NRI. CONCLUSION: Among women, only in the intermediate risk group,
      ECG abnormalities were independently associated with increased risk of developing
      CHD. Addition of the ECG abnormalities to the FRS improved the classification of
      coronary heart disease risk, especially in this group.

PMID- 22385985
TI  - Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related
      steatosis.
AB  - OBJECTIVES: HCV and NAFLD are associated with atherosclerosis in general
      population. The prevalence of atherosclerosis in chronic hepatitis C (CHC)
      patients is unknown. We hypothesized that HCV per se and HCV-related steatosis
      could favour atherosclerosis. Thus, in CHC patients we assessed: (a) the
      prevalence of atherosclerosis; (b) the role of HCV, cardio-metabolic risk factors
      and hepatic histology. METHODS: Overall, 803 subjects were enrolled: (A) 326
      patients with liver biopsy-proven treatment naive CHC (175 with and 151 without
      steatosis); (B) 477 age and gender matched controls, including 292 healthy
      subjects without steatosis (B1) and 185 with NAFLD (B2). Carotid atherosclerosis
      (CA), assessed by high-resolution B-mode ultrasonography, was categorized as
      either intima-media thickness (IMT: >1mm) or plaques (>= 1.5mm). RESULTS: CHC
      patients had a higher prevalence of CA than controls (53.7% vs 34.3%; p<0.0001).
      Younger CHC (<50 years) had a higher prevalence of CA than controls (34.0% vs
      16.0%; p<0.04). CHC patients without steatosis had a higher prevalence of CA than
      B1 controls (26.0% vs 14.8%; p<0.02). CHC with steatosis had a higher prevalence
      of CA than NAFLD patients (77.7% vs 57.8%, p<0.0001). Viral load was associated
      with serum CRP and fibrinogen levels; steatosis with metabolic syndrome, HOMA-IR,
      hyperhomocysteinemia and liver fibrosis. Viral load and steatosis were
      independently associated with CA. Diabetes and metabolic syndrome were associated
      with plaques. CONCLUSION: HCV infection is a risk factor for earlier and
      facilitated occurrence of CA via viral load and steatosis which modulate
      atherogenic factors such as inflammation and dysmetabolic milieu.

PMID- 22385986
TI  - CpGPAP: CpG island predictor analysis platform.
AB  - BACKGROUND: Genomic islands play an important role in medical, methylation and
      biological studies. To explore the region, we propose a CpG islands prediction
      analysis platform for genome sequence exploration (CpGPAP). RESULTS: CpGPAP is a
      web-based application that provides a user-friendly interface for predicting CpG
      islands in genome sequences or in user input sequences. The prediction algorithms
      supported in CpGPAP include complementary particle swarm optimization (CPSO), a
      complementary genetic algorithm (CGA) and other methods (CpGPlot, CpGProD and
      CpGIS) found in the literature. The CpGPAP platform is easy to use and has three
      main features (1) selection of the prediction algorithm; (2) graphic
      visualization of results; and (3) application of related tools and dataset
      downloads. These features allow the user to easily view CpG island results and
      download the relevant island data. CpGPAP is freely available at
      http://bio.kuas.edu.tw/CpGPAP/. CONCLUSIONS: The platform's supported algorithms
      (CPSO and CGA) provide a higher sensitivity and a higher correlation coefficient
      when compared to CpGPlot, CpGProD, CpGIS, and CpGcluster over an entire
      chromosome.

PMID- 22385987
TI  - Towards solving enigmas in electrical injury.
AB  - The paper by Park and colleagues in the previous issue of Critical Care
      highlights vascular changes in electrical injury and finds them to be relatively
      long-lasting and significant. This finding is consistent with long-lasting
      disability seen clinically in electrically injured patients. Furthermore, the
      authors report that the changes seen in the shocked part of the body are
      accompanied by similar changes that are measurable in other parts of the body but
      that are not involved with electric current. This latter finding is of
      significant importance. A psychological syndrome - consistent and predictable -
      exists following an electrical injury. The causation is enigmatic. Recent
      psychiatric research indicates the importance of circulating cortisol and brain
      derived neurotrophic factor (BDNF), which causes loss of hippocampal volume, in
      the genesis of depression. This psychiatric research has stimulated a speculative
      theory of the genesis of the psychological effects of electric shock. The paper
      by Park and colleagues is circumstantial support for the possibility that such a
      process is real and available.

PMID- 22385988
TI  - A breeding strategy to harness flavor diversity of Saccharomyces interspecific
      hybrids and minimize hydrogen sulfide production.
AB  - Industrial food-grade yeast strains are selected for traits that enhance their
      application in quality production processes. Wine yeasts are required to survive
      in the harsh environment of fermenting grape must, while at the same time
      contributing to wine quality by producing desirable aromas and flavors. For this
      reason, there are hundreds of wine yeasts available, exhibiting characteristics
      that make them suitable for different fermentation conditions and winemaking
      practices. As wine styles evolve and technical winemaking requirements change,
      however, it becomes necessary to improve existing strains. This becomes a
      laborious and costly process when the targets for improvement involve flavor
      compound production. Here, we demonstrate a new approach harnessing preexisting
      industrial yeast strains that carry desirable flavor phenotypes - low hydrogen
      sulfide (H(2) S) production and high ester production. A low-H(2) S Saccharomyces
      cerevisiae strain previously generated by chemical mutagenesis was hybridized
      independently with two ester-producing natural interspecies hybrids of S.
      cerevisiae and Saccharomyces kudriavzevii. Deficiencies in sporulation frequency
      and spore viability were overcome through use of complementary selectable traits,
      allowing successful isolation of several novel hybrids exhibiting both desired
      traits in a single round of selection.

PMID- 22385989
TI  - Environmental exposures and genitourinary malignancies.

PMID- 22385990
TI  - Bladder cancer risk from occupational and environmental exposures.
AB  - Approximately 50% of bladder cancer incidence in the United States has been
      attributed to known carcinogens, mainly from cigarette smoking. Following the
      identification of this important causative factor, many investigators have
      attempted to identify other major causes of bladder cancer in the environment.
      Genetic and epigenetic alterations related to carcinogenesis in the bladder have
      been linked to environmental and occupational factors unrelated to cigarette
      smoking and may account for a significant portion of bladder cancer cases in non
      smokers. The interaction between genetics and exposures may modulate bladder
      cancer risk and influence the differing incidence, progression, and mortality of
      this disease in different genders and races. Comparative molecular studies are
      underway to measure the relative effects of environment and inheritance to
      account for observed differences in the epidemiology of bladder cancer. The use
      of geospatial tools and population-based data will offer further insight into the
      environmentally-linked causes of bladder cancer.

PMID- 22385991
TI  - Environmental toxicology of testicular cancer.
AB  - OBJECTIVE: Testicular cancer incidence appears to be increasing. In many regions,
      industrialization results in the production of potentially carcinogenic
      environmental toxins. We review the available data linking environmental toxins
      to testicular germ cell tumors (TGCT). METHODS: A PubMed review of the English
      literature was performed to identify studies evaluating the relationship between
      environmental toxins and TGCT. RESULTS: Many environmental toxins have been
      implicated in the development of TGCT, including organochlorines, polychlorinated
      biphenyls, polyvinyl chlorides, phthalates, marijuana, and tobacco. Variable
      levels of evidence exist and significant study design limitations preclude a
      definitive etiologic role for individual environmental toxins. CONCLUSION:
      Environmental toxins may play an important but undetermined role in the
      development of TGCT. Further work is needed to evaluate specific toxins and TGCT
      carcinogenesis.

PMID- 22385992
TI  - Environmental exposures and prostate cancer.
AB  - Many malignancies have been linked to specific environmental exposures. Several
      environmental and occupational factors have been studied for an association to
      prostate cancer (CaP) risk. These include Agent Orange exposure, farming and
      pesticides, sunlight/ultraviolet radiation, as well as trace minerals used in
      tire and battery manufacturing. This manuscript reviews the literature on these
      environmental exposures and CaP.

PMID- 22385993
TI  - Environmental and modifiable risk factors in renal cell carcinoma.
AB  - OBJECTIVES: Prevention of disease requires a firm understanding of the relevant
      environmental and modifiable risk factors. We present a comprehensive review of
      these factors in renal cell carcinoma. MATERIALS AND METHODS: A literature search
      of the PubMed database was performed to identify clinical studies examining the
      relationship between environmental and modifiable factors in the development of
      renal cell carcinoma (terms utilized: kidney cancer; renal cell carcinoma; risk
      factors; environment; obesity; hypertension; trichloroethylene). An emphasis was
      placed on more recent studies. RESULTS: Case control and large cohort studies
      have examined the relationship of numerous environmental and modifiable factors
      and the risk of renal cell carcinoma. Of particular note are dose-dependent
      increases in smokers, the obese, and hypertensive patients. CONCLUSIONS:
      Environmental and modifiable risk factors contribute significantly to the risk of
      sporadic renal cell carcinoma. Emphasis should be placed on smoking cessation and
      hypertension control. Emerging evidence would suggest that dietary intake and
      quality impact renal cell carcinoma risk.

PMID- 22386005
TI  - Cingulum white matter in young women at risk of depression: the effect of family
      history and anhedonia.
AB  - BACKGROUND: Altered white matter microstructure in tracts integral to mood
      regulation networks could underlie vulnerability to major depressive disorder
      (MDD). Guided by functional magnetic resonance studies, we explored whether a
      positive family history of MDD (FH+) and anhedonia (reduced capacity for
      pleasure) were associated with altered white matter microstructure in the
      cingulum bundles and uncinate fasciculi. METHODS: Diffusion tensor magnetic
      resonance imaging data were acquired on 34 healthy female student volunteers
      (mean age 22 years). Exclusion criteria included other current or previous
      psychiatric disorder, current depression, and current psychotropic medication.
      Family history was determined using established criteria. Fiber tractography was
      performed for each individual for a priori tracts of interest and a comparison
      tract. Mean fractional anisotropy (FA), an index of microstructure, was
      calculated for each tract. RESULTS: Tracts were reconstructed in 18 FH+
      individuals and 15 FH- individuals, who did not differ by age or subclinical
      depressive symptoms. FH+ subjects had 3% to 5% lower FA in the right and left
      cingulum bundles than FH- individuals (p = .012, p = .059, respectively). Post
      hoc analysis demonstrated 8% lower FA in the left subgenual cingulate (p = .007).
      Hedonic tone correlated positively with FA in the right and left cingulum bundles
      (r = .342, p = .052; r = .477, p = .005, respectively), and the left subgenual
      cingulum (r = .500, p = .003). CONCLUSIONS: Both family history of MDD and
      subclinical anhedonia are associated with reduced FA in the bilateral cingulum
      bundles, particularly in the left subgenual cingulum. Altered cingulum white
      matter architecture is implicated in the etiology of MDD.

PMID- 22386006
TI  - A single oral dose of fructose induces some features of metabolic syndrome in
      rats: role of oxidative stress.
AB  - BACKGROUND AND AIMS: To determine if a single oral dose of fructose to rats
      reproduces some features of metabolic syndrome observed after chronic
      administration and if so, to investigate its mechanisms. METHODS AND RESULTS:
      Systolic blood pressure was measured in rats before and after oral administration
      of fructose, and in animals pretreated with lipoic acid, methyldopa, losartan or
      streptozotocin. In other rats, glucose, insulin, uric acid, and insulin
      sensitivity index, were determined before and after fructose or lipoic acid plus
      fructose. Glutathione was measured in liver before and after fructose
      administration. In aortic rings from other rats, incubation with mannitol,
      fructose, or fructose plus lipoic acid was evaluated on the relaxation by
      acetylcholine. Fructose produced a moderate increase in blood pressure, which was
      prevented by lipoic acid or streptozotocin. Methyldopa and losartan decreased the
      pressor response minimally. Fructose increased oxidized glutathione, plasma
      glucose, insulin and uric acid, and diminished the insulin sensitivity index, and
      the reduced glutathione. Lipoic acid prevented hyperglycemia and hyperuricemia,
      and improved the insulin sensitivity index. Finally, endothelial dysfunction was
      prevented by lipoic acid. CONCLUSION: A single dose of fructose reproduces some
      of the features of metabolic syndrome, most changes were caused by oxidative
      stress and insulin resistance.

PMID- 22386007
TI  - Drosophila Helical factor is an inducible protein acting as an immune-regulated
      cytokine in S2 cells.
AB  - The innate immunity of Drosophila melanogaster is based on cellular and humoral
      components. Drosophila Helical factor (Hf), is a molecule previously discovered
      using an in silico approach and whose expression is controlled by the immune
      deficiency (Imd) pathway. Here we present evidence demonstrating that Hf is an
      inducible protein constitutively produced by the S2 hemocyte-derived cell line.
      Hf expression is stimulated by bacterial extracts that specifically trigger the
      Imd pathway. In absence of any bacterial challenge, the recombinant form of Hf
      can influence the expression of the antimicrobial peptides (AMPs) defensin but
      not drosomycin. These data suggest that in vitro Hf is an inducible and immune
      regulated factor, with functions comparable to those of secreted vertebrate
      cytokines.

PMID- 22386008
TI  - Heterologous C-terminal signals effectively target fluorescent fusion proteins to
      leaf peroxisomes in diverse plant species.
AB  - Peroxisomes are functionally diverse organelles that are wholly dependent on
      import of nuclear-encoded proteins. The signals that direct proteins into these
      organelles are either found at the C-terminus (type 1 peroxisomal targeting
      signal; PTS1) or N-terminus (type 2 peroxisomal targeting signal; PTS2) of the
      protein. Based on a limited number of tests in heterologous systems, PTS1 signals
      appear to be conserved across species. To further test the generality of this
      conclusion and to establish the extent to which the PTS1 signals can be relied on
      for biotechnological purposes across species, we tested two PTS1 signals for
      their ability to target fluorescent proteins in diverse plant species. Transient
      assays following microprojectile bombardment showed that the six amino acid PTS1
      sequence (RAVARL) from spinach glycolate oxidase effectively targets green
      fluorescent fusion protein to the leaf peroxisomes in all 20 crops tested,
      including four monocots (sugarcane, wheat, corn and onion) and 16 dicots (carrot,
      cucumber, broccoli, tomato, lettuce, turnip, radish, cauliflower, cabbage,
      capsicum, celery, tobacco, petunia, beetroot, eggplant and coriander). Similarly,
      results indicated that the 10 amino acid PTS1 sequence (IHHPRELSRL) from pumpkin
      malate synthase effectively targets red fluorescent fusion protein to the leaf
      peroxisomes in all four crops tested including monocot (sugarcane) and dicot
      (cabbage, celery and pumpkin) species. These signal sequences should be useful
      metabolic engineering tools to direct recombinant proteins to the leaf
      peroxisomes in diverse plant species of biotechnological interest.

PMID- 22386010
TI  - What can be learned from China's health system?

PMID- 22386011
TI  - Drug control in marginalised communities.

PMID- 22386009
TI  - The impact on self-efficacy of different types of follow-up care and disease
      status in patients with rheumatoid arthritis--a randomized trial.
AB  - OBJECTIVE: To explore the impact from different types of outpatient care,
      demographic and disease related variables on self-efficacy beliefs (SE) in
      patients with established rheumatoid arthritis (RA) after completing an
      educational program. METHODS: 287 adult RA outpatients with low disease activity
      and moderate physical disability from two Danish rheumatology clinics were
      randomized for follow-up care. (1) planned rheumatologist's consultations, (2) a
      shared care model without planned consultations, (3) planned nursing
      consultations. The participants' SE were assessed by the Danish versions of the
      rheumatoid arthritis self-efficacy questionnaire (RASE) and the arthritis self
      efficacy scale (ASES). Data were collected at baseline, 3 months and one-year
      follow up and were explored in random intercept models. RESULTS: Following an
      educational programme the nursing group increased or stabilized their SE during
      the first year compared to the medical and the shared care group. SE in the
      shared care group did not differ significantly from the medical group. No
      difference between the groups was seen in disease activity at any time.
      CONCLUSION: Nursing consultations provide opportunities for maintenance of the
      patients' SE after patient education. PRACTICE IMPLICATIONS: Implementation of
      nursing consultations as part of follow-up care in patients with stable RA is
      recommended.

PMID- 22386012
TI  - The Royal College of Physicians of London roars.

PMID- 22386013
TI  - Tobacco control in China: small steps towards a giant leap.

PMID- 22386014
TI  - China's National Mental Health Law: a 26-year work in progress.

PMID- 22386015
TI  - Trends in China's reforms: the Rashomon effect.

PMID- 22386016
TI  - Enter the dragon: a Chinese epidemic of chronic kidney disease?

PMID- 22386017
TI  - A lung cancer molecular prognostic test ready for prime time.

PMID- 22386020
TI  - Wang Yu: protecting China's health.

PMID- 22386021
TI  - Shen Xiaoming: linking evidence to advocacy for health in China.

PMID- 22386022
TI  - Exercise and life expectancy.

PMID- 22386023
TI  - Exercise and life expectancy.

PMID- 22386024
TI  - Exercise and life expectancy.

PMID- 22386025
TI  - Exercise and life expectancy.

PMID- 22386027
TI  - Increased risk of coronary heart disease in female smokers.

PMID- 22386028
TI  - Increased risk of coronary heart disease in female smokers.

PMID- 22386029
TI  - Increased risk of coronary heart disease in female smokers.

PMID- 22386031
TI  - Who will fear the Commission on Global Governance for Health?

PMID- 22386032
TI  - JCVI response on hepatitis B vaccination.

PMID- 22386033
TI  - Challenges and opportunities for HIV/AIDS control in China.

PMID- 22386034
TI  - Trends in access to health services and financial protection in China between
      2003 and 2011: a cross-sectional study.
AB  - BACKGROUND: In the past decade, the Government of China initiated health-care
      reforms to achieve universal access to health care by 2020. We assessed trends in
      health-care access and financial protection between 2003, and 2011, nationwide.
      METHODS: We used data from the 2003, 2008, and 2011 National Health Services
      Survey (NHSS), which used multistage stratified cluster sampling to select 94 of
      2859 counties from China's 31 provinces and municipalities. The 2011 survey was
      done with a subset of the NHSS sampling frame to monitor key indicators after the
      national health-care reforms were announced in 2009. Three sets of indicators
      were chosen to measure trends in access to coverage, health-care activities, and
      financial protection. Data were disaggregated by urban or rural residence and by
      three geographical regions: east, central, and west, and by household income. We
      examined change in equity across and within regions. FINDINGS: The number of
      households interviewed was 57,023 in 2003, 56,456 in 2008, and 18,822 in 2011.
      Response rates were 98.3%, 95.0%, and 95.5%, respectively. The number of
      individuals interviewed was 193,689 in 2003, 177,501 in 2008, and 59,835 in 2011.
      Between 2003 and 2011, insurance coverage increased from 29.7% (57,526 of
      193,689) to 95.7% (57,262 of 59,835, p<0.0001). The average share of inpatient
      costs reimbursed from insurance increased from 14.4 (13.7-15.1) in 2003 to 46.9
      (44.7-49.1) in 2011 (p<0.0001). Hospital delivery rates averaged 95.8% (1219 of
      1272) in 2011. Hospital admissions increased 2.5 times to 8.8% (5288 of 59,835,
      p<0.0001) in 2011 from 3.6% (6981 of 193,689) in 2003. 12.9% of households (2425
      of 18,800) had catastrophic health expenses in 2011. Caesarean section rates
      increased from 19.2% (736 of 3835) to 36.3% (443 of 1221, p<0.0001) between 2003
      and 2011. INTERPRETATION: Remarkable increases in insurance coverage and
      inpatient reimbursement were accompanied by increased use and coverage of health
      care. Important advances have been made in achieving equal access to services and
      insurance coverage across and within regions. However, these increases have not
      been accompanied by reductions in catastrophic health expenses. With the
      achievement of basic health-services coverage, future challenges include stronger
      risk protection, and greater efficiency and quality of care. FUNDING: None.

PMID- 22386035
TI  - Prevalence of chronic kidney disease in China: a cross-sectional survey.
AB  - BACKGROUND: The prevalence of chronic kidney disease is high in developing
      countries. However, no national survey of chronic kidney disease has been done
      incorporating both estimated glomerular filtration rate (eGFR) and albuminuria in
      a developing country with the economic diversity of China. We aimed to measure
      the prevalence of chronic kidney disease in China with such a survey. METHODS: We
      did a cross-sectional survey of a nationally representative sample of Chinese
      adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1.73
      m(2) or the presence of albuminuria. Participants completed a lifestyle and
      medical history questionnaire and had their blood pressure measured, and blood
      and urine samples taken. Serum creatinine was measured and used to estimate
      glomerular filtration rate. Urinary albumin and creatinine were tested to assess
      albuminuria. The crude and adjusted prevalence of indicators of kidney damage
      were calculated and factors associated with the presence of chronic kidney
      disease analysed by logistic regression. FINDINGS: 50,550 people were invited to
      participate, of whom 47,204 agreed. The adjusted prevalence of eGFR less than 60
      mL/min per 1.73 m(2) was 1.7% (95% CI 1.5-1.9) and of albuminuria was 9.4% (8.9
      10.0). The overall prevalence of chronic kidney disease was 10.8% (10.2-11.3);
      therefore the number of patients with chronic kidney disease in China is
      estimated to be about 119.5 million (112.9-125.0 million). In rural areas,
      economic development was independently associated with the presence of
      albuminuria. The prevalence of chronic kidney disease was high in north (16.9%
      [15.1-18.7]) and southwest (18.3% [16.4-20.4]) regions compared with other
      regions. Other factors independently associated with kidney damage were age, sex,
      hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area
      of residence, and economic status. INTERPRETATION: Chronic kidney disease has
      become an important public health problem in China. Special attention should be
      paid to residents in economically improving rural areas and specific geographical
      regions in China. FUNDING: The Ministry of Science and Technology (China); the
      Science and Technology Commission of Shanghai; the National Natural Science
      Foundation of China; the Department of Health, Jiangsu Province; the Sichuan
      Science and Technology Department; the Ministry of Education (China); the
      International Society of Nephrology Research Committee; and the China Health and
      Medical Development Foundation.

PMID- 22386036
TI  - Early appraisal of China's huge and complex health-care reforms.
AB  - China's 3 year, CNY850 billion (US$125 billion) reform plan, launched in 2009,
      marked the first phase towards achieving comprehensive universal health coverage
      by 2020. The government's undertaking of systemic reform and its affirmation of
      its role in financing health care together with priorities for prevention,
      primary care, and redistribution of finance and human resources to poor regions
      are positive developments. Accomplishing nearly universal insurance coverage in
      such a short time is commendable. However, transformation of money and insurance
      coverage into cost-effective services is difficult when delivery of health care
      is hindered by waste, inefficiencies, poor quality of services, and scarcity and
      maldistribution of the qualified workforce. China must reform its incentive
      structures for providers, improve governance of public hospitals, and institute a
      stronger regulatory system, but these changes have been slowed by opposition from
      stakeholders and lack of implementation capacity. The pace of reform should be
      moderated to allow service providers to develop absorptive capacity. Independent,
      outcome-based monitoring and evaluation by a third-party are essential for mid
      course correction of the plans and to make officials and providers accountable.

PMID- 22386037
TI  - Urbanisation and health in China.
AB  - China has seen the largest human migration in history, and the country's rapid
      urbanisation has important consequences for public health. A provincial analysis
      of its urbanisation trends shows shifting and accelerating rural-to-urban
      migration across the country and accompanying rapid increases in city size and
      population. The growing disease burden in urban areas attributable to nutrition
      and lifestyle choices is a major public health challenge, as are troubling
      disparities in health-care access, vaccination coverage, and accidents and
      injuries in China's rural-to-urban migrant population. Urban environmental
      quality, including air and water pollution, contributes to disease both in urban
      and in rural areas, and traffic-related accidents pose a major public health
      threat as the country becomes increasingly motorised. To address the health
      challenges and maximise the benefits that accompany this rapid urbanisation,
      innovative health policies focused on the needs of migrants and research that
      could close knowledge gaps on urban population exposures are needed.

PMID- 22386038
TI  - Emergency medical rescue efforts after a major earthquake: lessons from the 2008
      Wenchuan earthquake.
AB  - Major earthquakes often result in incalculable environmental damage, loss of
      life, and threats to health. Tremendous progress has been made in response to
      many medical challenges resulting from earthquakes. However, emergency medical
      rescue is complicated, and great emphasis should be placed on its organisation to
      achieve the best results. The 2008 Wenchuan earthquake was one of the most
      devastating disasters in the past 10 years and caused more than 370,000
      casualties. The lessons learnt from the medical disaster relief effort and the
      subsequent knowledge gained about the regulation and capabilities of medical and
      military back-up teams should be widely disseminated. In this Review we summarise
      and analyse the emergency medical rescue efforts after the Wenchuan earthquake.
      Establishment of a national disaster medical response system, an active and
      effective commanding system, successful coordination between rescue forces and
      government agencies, effective treatment, a moderate, timely and correct public
      health response, and long-term psychological support are all crucial to reduce
      mortality and morbidity and promote overall effectiveness of rescue efforts after
      a major earthquake.

PMID- 22386039
TI  - Syncope: a rare manifestation of a common condition.

PMID- 22386040
TI  - Remote noninvasive allograft rejection monitoring for heart transplant
      recipients: study protocol for the novel evaluation with home electrocardiogram
      and remote transmission (NEW HEART) study.
AB  - BACKGROUND: Acute allograft rejection is a major cause of early mortality in the
      first year after heart transplantation in adults. Although endomyocardial biopsy
      (EMB) is not a perfect "gold standard" for a correct diagnosis of acute allograft
      rejection, it is considered the best available test and thus, is the current
      standard practice. Unfortunately, EMB is an invasive and costly procedure that is
      not without risk. Recent evidence suggests that acute allograft rejection causes
      delays in ventricular repolarization and thereby increases the cellular action
      potential duration resulting in a longer QT interval on the electrocardiogram
      (ECG). No prospective study to date has investigated whether such increases in
      the QT interval could provide early detection of acute allograft rejection.
      Therefore, in the Novel Evaluation With Home Electrocardiogram And Remote
      Transmission (NEW HEART) study, we plan to investigate the potential benefit of
      daily home QT interval monitoring to predict acute allograft rejection.
      METHODS/DESIGN: The NEW HEART study is a prospective, double-blind, multi-center
      descriptive research study. A sample of 325 adult heart transplant recipients
      will be recruited within six weeks of transplant from three sites in the United
      States. Subjects will receive the HeartViewTM ECG recorder and its companion
      Internet Transmitter, which will transmit the subject's ECG to a Core Laboratory.
      Subjects will be instructed to record and transmit an ECG recording daily for 6
      months. An increase in the QTC interval from the previous day of at least 25 ms
      that persists for 3 consecutive days will be considered abnormal. The number and
      grade of acute allograft rejection episodes, as well as all-cause mortality, will
      be collected for one year following transplant surgery. DISCUSSION: This study
      will provide "real world" prospective data to determine the sensitivity and
      specificity of QTC as an early non invasive marker of cellular rejection in
      transplant recipients during the first post-transplant year. A non-invasive
      indicator of early allograft rejection in heart transplant recipients has the
      potential to limit the number and severity of rejection episodes by reducing the
      time and cost of rejection surveillance and by shortening the time to recognition
      of rejection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01365806.

PMID- 22386041
TI  - The presence of arachnoiditis affects the characteristics of CSF flow in the
      spinal subarachnoid space: a modelling study.
AB  - Syringomyelia is a neurological disorder characterised by high pressure fluid
      filled cysts within the spinal cord. As syringomyelia is associated with
      abnormalities of the central nervous system that obstruct cerebrospinal fluid
      (CSF) flow, it is thought that changes in CSF dynamics play an important role in
      its pathogenesis. Using three-dimensional computational models of the spinal
      subarachnoid space (SAS), this study aims to determine SAS obstructions, such as
      arachnoiditis, change in CSF dynamics in the SAS. The geometry of the SAS was
      reconstructed from a series of MRI images. CSF is modelled as an incompressible
      Newtonian fluid with a dynamic viscosity of 1 mPa s. Three computational models
      simulated CSF flow in either the unobstructed SAS, or with the SAS obstructed by
      a porous region simulating dorsal or circumferential arachnoiditis. The
      permeability of this porous obstruction was varied for the model with dorsal
      arachnoiditis. The results show that arachnoiditis increases flow resistance in
      the SAS and this is accompanied by a modest increase in magnitude and/or shift in
      timing (with respect to the cardiac cycle) of the CSF pressure drop across the
      region of arachnoiditis. This study suggests that syrinx formation may be related
      to a change in temporal CSF pulse pressure dynamics.

PMID- 22386042
TI  - A novel in vitro flow system for changing flow direction on endothelial cells.
AB  - Atherosclerotic plaques localize to regions of flow disturbance, i.e.
      bifurcations, branch points and regions of high curvature. Shear stress in these
      regions can be multi-directional due to complex flow patterns such as time
      varying vortices. However, commonly used in vitro flow models are incapable of
      changing flow orientation to any direction other than the reverse. We have
      developed a novel in vitro flow system to enable changes in flow direction to any
      angle. When cells were pre-aligned in laminar shear, and then rotated 90 degrees
      , cells re-aligned over 24 h. Re-alignment involved actin remodeling by gradual
      rotation of actin stress fibers. This device will enable that analysis of how
      endothelial cells sense changes in flow direction as occur in vivo.

PMID- 22386043
TI  - Association between inhaled nitric oxide treatment and long-term pulmonary
      function in survivors of acute respiratory distress syndrome.
AB  - INTRODUCTION: Assessment of treatments for acute respiratory distress syndrome
      (ARDS) has focused on short-term outcomes (for example, mortality); little
      information exists regarding long-term effects of ARDS treatment. Survivors of
      ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities
      and pulmonary gas exchange impairment. A 2004 prospective randomized placebo
      controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO)
      in patients with non-septic ARDS; the primary endpoint was days alive and off
      assisted breathing. This analysis examined potential effects of iNO or placebo on
      pulmonary function six months post-treatment in ARDS survivors from that original
      study. METHODS: ARDS survivors (N = 92) from a large-scale randomized, placebo
      controlled study evaluating mortality after either 5 ppm iNO or placebo for up to
      28 days were assessed six months post-treatment. Pulmonary function testing
      across seven parameters was conducted. RESULTS: At 6 months post-treatment,
      results indicated significantly better absolute values for iNO versus placebo for
      mean +/- SD total lung capacity (TLC, 5.54 +/- 1.42 vs. 4.81 +/- 1.00; P =
      0.026). There were also significantly better values for mean +/- SD percent
      predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 +/-
      21.21 vs. 69.51 +/- 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 +/-
      19.37 vs. 69.84 +/- 27.40; P = 0.019), c) FEV1/FVC (96.14 +/- 13.79 vs. 87.92 +/-
      19.77; P = 0.033), and d) TLC (93.33 +/- 18.21 vs. 76.10 +/- 21.84; P < 0.001).
      Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced
      expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO
      diffusion. CONCLUSIONS: ARDS patients surviving after treatment with low-dose iNO
      had significantly better values for select pulmonary function tests at six months
      post-treatment than placebo-treated patients. Further trials are warranted to
      determine the effects of iNO on chronic lung function in ARDS survivors, a factor
      in long-term morbidity and quality of life in this population. TRIAL
      REGISTRATION: A Double-blind, Randomized, Placebo-controlled, Dose-response Study
      of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome.
      NCT number: ISRCTN53268296.

PMID- 22386044
TI  - The effects of mouthguards on the athletic ability of professional golfers.
AB  - The purpose of this study was to determine the effect of stabilization splints
      and mouthguards on the athletic ability of professional golfers. For this study,
      eight professional golfers with a mean age of 20.5 were selected. These
      participants performed four trials of 10 driver swings and 10 putts with or
      without a stabilization splint (control group) or mouthguard. For the 4th trial,
      the splints were adjusted using a simple blind test so that the participants were
      unaware of the unilateral molar contact. The drive distance, club head speed,
      initial ball speed, and putting accuracy were compared and analyzed before and
      after the application of equal bilateral molar occlusion. When the bilateral
      molar occlusion was applied using a mouthguard or stabilization splint, the club
      head speed and driving distance in the presence of the oral appliances were
      significantly increased compared with those without the presence of either
      appliance (P < 0.05). Alternatively, the initial ball speed and putting accuracy
      in the presence of these appliances were increased compared with those without
      the presence of an appliance; however, this effect was not statistically
      significant. When the mouthguards or stabilization splints were adjusted to
      result in unilateral molar occlusion, the club head speed and driving distance in
      the presence of the appliances were significantly decreased compared with those
      that were obtained without these appliances (P < 0.05). The initial ball speed
      and the putting accuracy were not affected by the use of the appliances. No
      difference was observed in the effectiveness of the stabilization splint and
      mouthguard when bilateral molar occlusion was performed. The occlusion stability
      that results from stabilization splints and mouthguards is thought to increase
      the club head speed and driving distance in professional golf players.

PMID- 22386045
TI  - ERP correlates of pitch error detection in complex tone and voice auditory
      feedback with missing fundamental.
AB  - Previous studies have shown that the pitch of a sound is perceived in the absence
      of its fundamental frequency (F0), suggesting that a distinct mechanism may
      resolve pitch based on a pattern that exists between harmonic frequencies. The
      present study investigated whether such a mechanism is active during voice pitch
      control. ERPs were recorded in response to +200 cents pitch shifts in the
      auditory feedback of self-vocalizations and complex tones with and without the
      F0. The absence of the fundamental induced no difference in ERP latencies.
      However, a right-hemisphere difference was found in the N1 amplitudes with larger
      responses to complex tones that included the fundamental compared to when it was
      missing. The P1 and N1 latencies were shorter in the left hemisphere, and the N1
      and P2 amplitudes were larger bilaterally for pitch shifts in voice and complex
      tones compared with pure tones. These findings suggest hemispheric differences in
      neural encoding of pitch in sounds with missing fundamental. Data from the
      present study suggest that the right cortical auditory areas, thought to be
      specialized for spectral processing, may utilize different mechanisms to resolve
      pitch in sounds with missing fundamental. The left hemisphere seems to perform
      faster processing to resolve pitch based on the rate of temporal variations in
      complex sounds compared with pure tones. These effects indicate that the
      differential neural processing of pitch in the left and right hemispheres may
      enable the audio-vocal system to detect temporal and spectral variations in the
      auditory feedback for vocal pitch control.

PMID- 22386046
TI  - The effectiveness of sub-group specific manual therapy for low back pain: a
      systematic review.
AB  - BACKGROUND: Manual therapy is frequently used to treat low back pain (LBP), but
      evidence of its effectiveness is limited. One explanation may be sample
      heterogeneity and inadequate sub-grouping of participants in randomized
      controlled trials (RCTs) where manual therapy has not been targeted toward those
      likely to respond. OBJECTIVES: To determine the effectiveness of specific manual
      therapy provided to sub-groups of participants identified as likely to respond to
      manual therapy. DATA SOURCES: A systematic search of electronic databases of
      MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled trials
      (CENTRAL). TRIAL ELIGIBILITY CRITERIA: RCTs on manual therapy for participants
      identified as belonging to a sub-group of LBP likely to respond to manual therapy
      were included. TRIAL APPRAISAL AND SYNTHESIS METHODS: Identified trials were
      assessed for eligibility. Data from included trials were extracted by two authors
      independently. Risk of bias in each trial was assessed using the PEDro scale and
      the overall quality of evidence rated according to the GRADE domains. Treatment
      effect sizes and 95% confidence intervals were calculated for pain and activity.
      RESULTS: Seven RCTs were included in the review. Clinical and statistical
      heterogeneity precluded meta-analysis. Significant treatment effects were found
      favouring sub-group specific manual therapy over a number of comparison
      treatments for pain and activity at short and intermediate follow-up. However,
      the overall GRADE quality of evidence was very low. CONCLUSIONS: This review
      found preliminary evidence supporting the effectiveness of sub-group specific
      manual therapy. Further high quality research on LBP sub-groups is required.

PMID- 22386047
TI  - Fronto-temporo-insula gray matter alterations of first-episode, drug-naive and
      very late-onset panic disorder patients.
AB  - OBJECTIVE: There is no voxel-based morphometry study for first-episode, drug
      naive and very late-onset panic disorder patients. Besides, differences of onset
      age might represent different clinical subgroups. Therefore we designed this
      study to investigate gray matter deficits in this subgroup of patients. METHOD:
      30 patients and 21 normal controls were enrolled into our study. They all
      received 3T magnetic resonance imaging acquisition for the structural imaging of
      brain. All the structural images were processed and analyzed to estimate the
      differences of gray matter volumes between patients and controls. We utilized
      optimized voxel-based morphometry function implemented in the FSL (FMRIB Software
      Library) with the agoraphobia, global brain volume, age, gender and duration of
      illness as covariates. We also performed the voxel-wise linear regression between
      clinical rating scale scores and gray matter volumes of brain to confirm results
      of optimized voxel-based morphometry and significant region for physiopathology
      of very late-onset PD. RESULTS: First-episode, drug-naive and very late-onset
      panic disorder patients had lower gray matter volumes in left orbitofrontal
      cortex, left inferior frontal cortex, left superior temporal gyrus and right
      insula when they were compared to controls (corrected p<0.005, multiple
      comparisons, cluster threshold: 30 voxels). A negative correlation between PDSS
      and GMV was observed in right insula using general linear model voxel-wise
      analysis with age and gender corrected. CONCLUSION: Fronto-temporo-insula gray
      matter deficits might represent the structural pathophysiology of first-episode,
      drug-naive and very late-onset panic disorder.

PMID- 22386048
TI  - Cardio-respiratory coupling in untreated patients with major depression.
AB  - BACKGROUND: Depressive disorders are known to be associated with higher risks of
      cardiovascular diseases. Several studies have reported an imbalance within the
      autonomic nervous system (ANS) as one putative cause. Previous investigations
      showed decreased cardio-respiratory coupling in depressive patients that were
      treated with nortriptyline. We aimed to compare parameters of heart rate
      variability and cardio-respiratory coupling between unmedicated patients
      suffering from major depressive disorder (MDD) and healthy controls in order to
      further understand autonomic dysfunction in the disease. METHODS: We investigated
      eighteen unmedicated patients with major depressive disorder and eighteen matched
      healthy controls. Electrocardiogram and respiratory signals were obtained during
      a twenty minute resting period. Time- and frequency based parameters of HRV,
      respiratory sinus arrhythmia (RSA), approximate entropy of heart rate (ApEn(RR))
      and respiratory rate (ApEn(Resp)) were calculated. Additionally, cross-ApEn
      between RR-intervals and respiration time series was determined, reflecting
      coupling of both signals. RESULTS: Patients showed an increased heart rate and
      LF/HF-ratio. Respiratory sinus arrhythmia (RSA) and ApEn(RR) were reduced in
      patients in comparison to controls. Breathing rate, ApEn(Resp) and cross-ApEn did
      not differ between the two groups. DISCUSSION: Increased heart rate, increased
      LF/HF-ratio, reduced RSA and reduced ApEn(RR) indicate a decrease of cardiac
      vagal modulation in depressive patients. No difference of cardio-respiratory
      coupling was observed. Respiratory parameters and cross-ApEn did not differ
      between both groups, and thus we conclude that diminished vagal modulation is
      mainly limited to cardiac modulation.

PMID- 22386049
TI  - PCLO gene: its role in vulnerability to major depressive disorder.
AB  - BACKGROUND: A recent genome-wide association study on Major Depressive Disorder
      (MDD) identified a specific association with a non-synonymous polymorphism
      (rs2522833) of a gene encoding the presynaptic protein piccolo (PCLO). A high
      percentage of patients who develop MDD have particular temperamental traits, such
      as passivity, pessimism, indecisiveness, and low self-esteem, which are related
      to the subsequent development of depression. The aims of this study were to
      perform a replicate case-control study and to conduct the first association study
      between the rs2522833 polymorphism and depression-related personality traits
      using the Temperament and Character Inventory (TCI) in a healthy subject sample.
      METHODS: A total of 522 MDD patients and 375 healthy volunteers were enrolled in
      the study. Two hundred and forty-six controls agreed to fill out the TCI.
      RESULTS: The results showed that rs2522833 CC homozygotes were more frequent
      among the depressed patients than in the controls (p<0.01). The C allele
      distribution showed a trend in the same direction (p=0.08). Among controls, we
      found that the C allele carriers were associated with personality traits
      increasing vulnerability to depression, including higher Harm Avoidance (HA) and
      lower in Novelty Seeking (NS). In particular, C allele carriers were more fearful
      (HA2) and fatigable (HA4), and less impulsive/more deliberate (NS2) and less
      extravagant/more frugal (NS3). LIMITATIONS: The absence of possible epistatic
      interaction effect. CONCLUSIONS: These results provide further support for the
      involvement of the PCLO gene in MDD and show that this effect may be mediated by
      influencing personality traits that increase the risk of major depression.

PMID- 22386050
TI  - Family history, body mass index, selected dietary factors, menstrual history, and
      risk of moderate to severe acne in adolescents and young adults.
AB  - BACKGROUND: Genetic and environmental components may contribute to acne
      causation. OBJECTIVE: We sought to assess the impact of family history, personal
      habits, dietary factors, and menstrual history on a new diagnosis of moderate to
      severe acne. METHODS: We conducted a case-control study in dermatologic
      outpatient clinics in Italy. Cases (205) were consecutive those receiving a new
      diagnosis of moderate to severe acne. Control subjects (358) were people with no
      or mild acne, coming for a dermatologic consultation other than for acne.
      RESULTS: Moderate to severe acne was strongly associated with a family history of
      acne in first-degree relatives (odds ratio 3.41, 95% confidence interval 2.31
      5.05). The risk was reduced in people with lower body mass index with a more
      pronounced effect in male compared with female individuals. No association with
      smoking emerged. The risk increased with increased milk consumption (odds ratio
      1.78, 95% confidence interval 1.22-2.59) in those consuming more than 3 portions
      per week. The association was more marked for skim than for whole milk.
      Consumption of fish was associated with a protective effect (odds ratio 0.68, 95%
      confidence interval 0.47-0.99). No association emerged between menstrual
      variables and acne risk. LIMITATIONS: Some degree of overmatching may arise from
      choosing dermatologic control subjects and from inclusion of mild acne in the
      control group. CONCLUSIONS: Family history, body mass index, and diet may
      influence the risk of moderate to severe acne. The influence of environmental and
      dietetic factors in acne should be further explored.

PMID- 22386051
TI  - Multicenter clinical trial of a home-use nonablative fractional laser device for
      wrinkle reduction.
AB  - BACKGROUND: Until now, nonablative fractional treatments could only be delivered
      in an office setting by trained professionals. OBJECTIVE: The goal of this work
      was to perform clinical testing of a nonablative fractional laser device designed
      for home-use. METHODS: This multicenter trial consisted of two clinical studies
      with slightly varying treatment protocols in which subjects performed at-home
      treatments of periorbital wrinkles using a handheld nonablative fractional laser.
      Both studies included an active treatment phase (daily treatments) and a
      maintenance phase (twice-weekly treatments). In all, 36 subjects were followed up
      for as long as 5 months after completion of the maintenance phase and 90 subjects
      were followed up until the completion of the maintenance phase. Evaluations
      included in-person investigator assessment, independent blinded review of high
      resolution images using the Fitzpatrick Wrinkle Scale, and subject self
      assessment. RESULTS: All 124 subjects who completed the study were able to use
      the device following written instructions for use. Treatments were well tolerated
      with good protocol compliance. Independent blinded evaluations by a panel of
      physicians showed Fitzpatrick Wrinkle Scale score improvement by one or more
      grades in 90% of subjects at the completion of the active phase and in 79% of
      subjects at the completion of the maintenance phase. The most prevalent side
      effect was transient posttreatment erythema. LIMITATIONS: Lack of a control group
      and single-blinded study groups were limitations. CONCLUSION: Safety testing with
      self-applications by users demonstrated the utility of the device for home use.
      Independent blinded review of clinical images confirmed the device's proficiency
      for improving periorbital wrinkles.

PMID- 22386052
TI  - "Inverted corner" for sleeve gastrectomy.

PMID- 22386053
TI  - Six-year changes in health-related quality of life in gastric bypass patients
      versus obese comparison groups.
AB  - BACKGROUND: Few studies have evaluated the long-term outcomes of bariatric
      surgery patients in relation to obese individuals not participating in weight
      loss interventions. Our objective was to evaluate the 6-year changes in health
      related quality of life (HRQOL) in gastric bypass (GB) patients versus 2 obese
      groups not undergoing surgical weight loss. The study setting was a bariatric
      surgery practice. METHODS: A total of 323 GB patients were compared with 257
      individuals who sought but did not undergo gastric bypass and 272 population
      based obese individuals using weight-specific (impact of weight on quality of
      life-lite) and general (medical outcomes study short-form 36 health survey) HRQOL
      questionnaires at baseline and 2 and 6 years later. RESULTS: At 6 years, compared
      with the controls, the GB group exhibited significant improvements in all domains
      of weight-specific and most domains of general HRQOL (i.e., all physical and some
      mental/psychosocial). The 6-year percentage of excess weight loss correlated
      significantly with improvements in both weight-specific and physical HRQOL. The
      HRQOL scores were fairly stable from 2 to 6 years for the GB group, with small
      decreases in HRQOL corresponding to some weight regain. CONCLUSIONS: GB patients
      demonstrated significant improvements in most aspects of HRQOL at 6 years
      compared with 2 nonsurgical obese groups. Despite some weight regain and small
      decreases in HRQOL from 2 to 6 years postoperatively, the HRQOL was relatively
      stable. These results support the effectiveness of weight loss achieved with
      gastric bypass surgery for improving and maintaining long-term HRQOL.

PMID- 22386054
TI  - Evidence of recombination and positive selection in cetacean papillomaviruses.
AB  - Papillomaviruses (PVs) are small DNA viruses that have been associated with
      increased epithelial proliferation. Over one hundred PV types have been
      identified in humans; however, only three have been identified in bottlenose
      dolphins (Tursiops truncatus) to date. Using rolling circle amplification and
      degenerate PCR, we identified four novel PV genomes of bottlenose dolphins.
      TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was
      identified in normal genital mucosa. Bayesian analysis of the full-length L1
      genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus
      while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the
      E1 gene did not distinguish these genera, implying that these genes may not share
      a common history, consistent with recombination. Recombination analyses
      identified several probable events. Signals of positive selection were found
      mostly in the E1 and E2 genes. Recombination and diversifying selection pressures
      constitute important driving forces of cetacean PV evolution.

PMID- 22386055
TI  - Structural evolution of the P22-like phages: comparison of Sf6 and P22 procapsid
      and virion architectures.
AB  - Coat proteins of tailed, dsDNA phages and in herpesviruses include a conserved
      core similar to the bacteriophage HK97 subunit. This core is often embellished
      with other domains such as the telokin Ig-like domain of phage P22. Eighty-six
      P22-like phages and prophages with sequenced genomes share a similar set of
      virion assembly genes and, based on comparisons of twelve viral assembly proteins
      (structural and assembly/packaging chaperones), these phages are classified into
      three groups (P22-like, Sf6-like, and CUS-3-like). We used cryo-electron
      microscopy and 3D image reconstruction to determine the structures of Sf6
      procapsids and virions (~7A resolution), and the structure of the entire,
      asymmetric Sf6 virion (16-A resolution). The Sf6 coat protein is similar to that
      of P22 yet it has differences in the telokin domain and in its overall quaternary
      organization. Thermal stability and agarose gel experiments show that Sf6 virions
      are slightly less stable than those of P22. Finally, bacterial host outer
      membrane proteins A and C were identified in lipid vesicles that co-purify with
      Sf6 particles, but are not components of the capsid.

PMID- 22386056
TI  - HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase
      interaction and effects on macrophage infection.
AB  - HIV-2 Vpx, a virus-associated accessory protein, is critical for infection of non
      dividing myeloid cells. To understand the function of Vpx ubiquitination,
      interaction with an E3 ubiquitin ligase complex, and ability to overcome an
      inhibition of reverse transcription, we analyzed Vpx lysine mutants for their
      function and replication capability in macrophages. Both Wt Vpx and Vpx TA
      (lysine-less Vpx) localized to the cytoplasm and nucleus in HeLa cells. All HIV-2
      Vpx lysine mutants were functional in virion packaging. However, ubiquitination
      was absent with Vpx TA and Vpx K84A mutants, indicating a lack of ubiquitin on
      positions K68 and K77. Mutants Vpx K68A and K77A were unable to infect
      macrophages due to impaired reverse transcription from loss of interaction with
      the ubiquitin substrate receptor, DCAF1. Even though Vpx K84A lacked
      ubiquitination, it bound DCAF1, and infected macrophages comparable to Wt Vpx.

PMID- 22386057
TI  - Evaluation of highly polar ionic liquid gas chromatographic column for the
      determination of the fatty acids in milk fat.
AB  - The SLB-IL111, a new ionic liquid capillary column for gas chromatography
      available from Supelco Inc., was recently shown to provide enhanced separation of
      unsaturated geometric and positional isomers of fatty acid (FAs) when it was
      compared to cyanopropylsiloxane (CPS) columns currently recommended for the
      analysis of fatty acid methyl esters (FAMEs). A 200 m SLB-IL111 capillary column,
      operated under a combined temperature and eluent flow gradient, was successfully
      used to resolve most of the FAs contained in milk fat in a single 80 min
      chromatographic separation. The selected chromatographic conditions provided a
      balanced, simultaneous separation of short-chain (from 4:0), long-chain
      polyunsaturated fatty acids (PUFAs), and most of the unsaturated FA
      positional/geometric isomers contained in milk fat. Among the monounsaturated
      fatty acids (MUFAs), these conditions separated t11-18:1 and t10-18:1 FAs, the
      two most abundant trans fatty acids (t-FA) contained in most dairy products.
      These t-FAs reportedly have different biological activities. The conjugated
      linoleic acid (CLA) isomers commonly found in dairy products were separated from
      each other, including t7,c9-18:2 from c9,t11-18:2, which eliminated the need for
      their complementary silver ion HPLC analysis. The application of the SLB-IL111
      column provided a complementary elution profile of FAMEs to those obtained by CPS
      columns, allowing for a more comprehensive FA analysis of total milk fat. The
      FAMEs were identified by the use of available reference materials, previously
      synthesized and characterized reference mixtures, and prior separations of the
      milk fat FAMEs by silver ion chromatography based on the number/geometry of
      double bonds.

PMID- 22386058
TI  - Investigation of retention behavior of polychlorinated biphenyl congeners on 18
      different HRGC columns using molecular surface average local ionization energy
      descriptors.
AB  - In this paper, based on the general interaction properties function (GIPF) family
      descriptors computed at the B3LYP/6-31G* level in Gaussian98 software, a
      significant quantitative structure-retention relationship (QSRR) models for the
      high resolution gas chromatographic relative retention time (HRGC-RRT) of all PCB
      congeners on 18 different HRGC capillary columns were constructed by using
      multiple linear regression (MLR) analysis, following the guidelines for
      development and validation of QSRR models. By means of the elimination selection
      stepwise regression algorithms, the molecular surface average local ionization
      energy was selected as one-parameter univariate linear regression to develop a
      QSRR model for prediction of GC-RRT of PCBs on each stationary phase. The
      accuracy of all developed models was confirmed using different types of internal
      and external procedures. A successful interpretation of the complex relationship
      between HRGC-RRTs of PCBs and the chemical structures was achieved by QSRR.

PMID- 22386059
TI  - An improved hollow fiber solvent-stir bar microextraction for the
      preconcentration of anabolic steroids in biological matrix with determination by
      gas chromatography-mass spectrometry.
AB  - In this paper, a convenient and self-assembled hollow fiber solvent-stir bar
      microextraction (HF-SSBME) device was developed, which could stir by itself. In
      the extraction process, the proposed device made the solvent "bar" not floating
      at the sample solution and exposing to air while organic solvents outside hollow
      fiber always wrapped with donor phase solvent, which reduced the vaporization of
      organic solvents. This design could improve the precisions and recoveries of
      experiments. For evaluating the device, seven anabolic steroids (prasterone,
      5alpha-androstane-3alpha, 17beta-diol, methandriol, 19-norandrostenediol,
      androstenediol, methyltestosterone and methandienone) were used as model analytes
      and extraction conditions such as type and volume of organic solvents, agitation
      speed, extraction time, extraction temperature and salt addition were studied in
      detail. Under the optimum conditions (15 MUL toluene, 40  degrees C, stirring at
      750 rpm for 30 min with 1.5 g sodium chloride addition in 20.0 mL donor phase),
      the linear ranges of anabolic steroids were 0.25-200 ng mL(-1) with gas
      chromatography-mass spectrometry. The limits of detection were lower than 0.10 ng
      mL(-1). The recoveries and precisions in spiked urine and hair samples were
      between 73.97-93.56% and 2.18-4.47% (n=5). HF-SSBME method combined the
      intrinsical merits of hollow fiber with the superiority of the proposed self
      stirring device which can be developed to two-phase, three-phase and in situ
      derivatization modes with wide prospect of application. Besides, the pedestal of
      this proposed device can be converted to fix stir bar in stir bar sorptive
      extraction (SBSE) method.

PMID- 22386060
TI  - A systematic review of cross-cultural comparison studies of child, parent, and
      health professional outcomes associated with pediatric medical procedures.
AB  - The purpose of this review was to evaluate systematically all published and
      unpublished research concerning culture and medical procedural pain in children.
      Databases, reference lists, and electronic list servers were searched as data
      sources. Fifteen studies met the inclusion criteria. Most studies (80%) were
      conducted solely in the United States comparing Caucasian American groups to
      other local subculture(s) (ie, African American, Hispanic, or Japanese). The
      studies compared, cross culturally, pediatric pain-related outcomes in children,
      parents and/or health professionals. The medical procedural experiences included
      surgery, immunization, spinal tap, bone marrow aspiration, needle procedures,
      orthopedic, and wound-related injuries. The evidence published to date suggests
      that cultural factors may be associated with children's pain experiences when
      elicited by medical procedural pain, specifically children's pain behavior.
      Nevertheless, research using more sophisticated research methods is needed to
      develop culturally sensitive behavioral pain measures. Measures that include
      physiological pain parameters in addition to other behavioral outcomes may be
      helpful. Culturally comparative research would benefit from the use of
      theoretical frameworks to advance our understanding of the cultural underpinnings
      of child pain development and guide future research. PERSPECTIVE: The current
      evidence supports that children and parents belonging to cultural minority
      groups, and in need of health care, are a vulnerable population. Together,
      researchers and clinicians are encouraged to explore this understudied area, and
      take advantage of sophisticated methods developed by disciplines like cross
      cultural psychology.

PMID- 22386061
TI  - The Journal of Neuroradiology: Future prospects.

PMID- 22386062
TI  - Negative- versus positive-pressure ventilation in intubated patients with acute
      respiratory distress syndrome.
AB  - INTRODUCTION: Recent experimental data suggest that continuous external negative
      pressure ventilation (CENPV) results in better oxygenation and less lung injury
      than continuous positive-pressure ventilation (CPPV). The effects of CENPV on
      patients with acute respiratory distress syndrome (ARDS) remain unknown. METHODS:
      We compared 2 h CENPV in a tankrespirator ("iron lung") with 2 h CPPV. The six
      intubated patients developed ARDS after pulmonary thrombectomy (n = 1),
      aspiration (n = 3), sepsis (n = 1) or both (n = 1). We used a tidal volume of 6
      ml/kg predicted body weight and matched lung volumes at end expiration.
      Haemodynamics were assessed using the pulse contour cardiac output (PiCCO)
      system, and pressure measurements were referenced to atmospheric pressure.
      RESULTS: CENPV resulted in better oxygenation compared to CPPV (median ratio of
      arterial oxygen pressure to fraction of inspired oxygen of 345 mmHg (minimum
      maximum 183 to 438 mmHg) vs 256 mmHg (minimum-maximum 123 to 419 mmHg) (P <
      0.05). Tank pressures were -32.5 cmH2O (minimum-maximum -30 to -43) at end
      inspiration and -15 cmH2O (minimum-maximum -15 to -19 cmH2O) at end expiration.
      NO Inspiratory transpulmonary pressures decreased (P = 0.04) and airway pressures
      were considerably lower at inspiration (-1.5 cmH2O (minimum-maximum -3 to 0
      cmH2O) vs 34.5 cmH2O (minimum-maximum 30 to 47 cmH2O), P = 0.03) and expiration
      (4.5 cmH2O (minimum-maximum 2 to 5) vs 16 cmH2O (minimum-maximum 16 to 23), P
      =0.03). During CENPV, intraabdominal pressures decreased from 20.5 mmHg (12 to 30
      mmHg) to 1 mmHg (minimum-maximum -7 to 5 mmHg) (P = 0.03). Arterial pressures
      decreased by approximately 10 mmHg and central venous pressures by 18 mmHg.
      Intrathoracic blood volume indices and cardiac indices increased at the
      initiation of CENPV by 15% and 20% (P < 0.05), respectively. Heart rate and
      extravascular lung water indices remained unchanged. CONCLUSIONS: CENPV with a
      tank respirator improved gas exchange in patients with ARDS at lower
      transpulmonary, airway and intraabdominal pressures and, at least initially
      improving haemodynamics. Our observations encourage the consideration of further
      studies on the physiological effects and the clinical effectiveness of CENPV in
      patients with ARDS.

PMID- 22386063
TI  - Reversible cerebral vasoconstriction syndrome associated with brain parenchymal
      hemorrhage.
AB  - We described a 7-year-old girl with reversible cerebral vasoconstriction syndrome
      associated with brain parenchymal hemorrhage. She initially presented with high
      fever and pancytopenia, leading to a diagnosis of most severe type aplastic
      anemia. We treated her with cyclosporine, methylprednisolone and anti-thymocyte
      globulin. Thereafter she recurrently complained of a very severe headache called
      as thunderclap, and finally exhibited loss of consciousness. Brain imaging
      revealed massive parenchymal hemorrhage between the left occipital and parietal
      lobes on computed tomography, and diffuse cerebral vasoconstriction on magnetic
      resonance angiography. The cerebral vasoconstriction resolved within two months,
      and thus we diagnosed her as having reversible cerebral vasoconstriction syndrome
      associated with brain parenchymal hemorrhage. This syndrome has been frequently
      reported in adult females, but rarely in children. However, even in children, a
      so called thunderclap headache may become a clue for the diagnosis of reversible
      cerebral vasoconstriction syndrome, especially in cases taking immunosuppressive
      agents. Immediate magnetic resonance angiography is essential to diagnose this
      syndrome, and a prompt application of calcium channel inhibitors should be
      considered to resolve constriction of the vessels and to prevent subsequent brain
      damage.

PMID- 22386064
TI  - The FIGO systems for nomenclature and classification of causes of abnormal
      uterine bleeding in the reproductive years: who needs them?
AB  - In November 2010, the International Federation of Gynecology and Obstetrics
      formally accepted a new classification system for causes of abnormal uterine
      bleeding in the reproductive years. The system, based on the acronym PALM-COEIN
      (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy,
      ovulatory disorders, endometrial causes, iatrogenic, not classified) was
      developed in response to concerns about the design and interpretation of basic
      science and clinical investigation that relates to the problem of abnormal
      uterine bleeding. A system of nomenclature for the description of normal uterine
      bleeding and the various symptoms that comprise abnormal bleeding has also been
      included. This article describes the rationale, the structured methods that
      involved stakeholders worldwide, and the suggested use of the International
      Federation of Gynecology and Obstetrics system for research, education, and
      clinical care. Investigators in the field are encouraged to use the system in the
      design of their abnormal uterine bleeding-related research because it is an
      approach that should improve our understanding and management of this often
      perplexing clinical condition.

PMID- 22386066
TI  - Association of FAS -1377 G>A and FAS -670 A>G functional polymorphisms of FAS
      gene of cell death pathway with recurrent early pregnancy loss risk.
AB  - Apoptosis during the early stages of pregnancy enables the remodeling of the
      uterus for proper placentation. Apoptosis in the maternal activated cytotoxic T
      lymphocytes allows maternal immune tolerance to pregnancy and in glandular and
      stromal cells it helps with trophoblastic endometrial invasion. FAS gene is
      expressed at the maternal-fetal interface and is involved in the regulation of
      immune response and implantation. Altered FAS expression may result in altered
      apoptosis and ultimately affects both immune response and implantation. FAS -1377
      G>A and FAS -670 A>G functional polymorphisms in the promoter region of FAS gene
      modulate its expression at transcriptional level. In a case-control study the
      contribution of FAS -1377 G>A and FAS -670 A>G polymorphisms to the risk of
      recurrent early pregnancy loss (REPL) was evaluated. DNA from 134 cases with a
      history of three or more REPL and 124 healthy controls with successful pregnancy
      outcomes were genotyped through PCR-RFLP. DNA sequencing was used to ascertain
      PCR-RFLP results. The genotype and allele frequencies for FAS -1377 G>A and FAS 
      670 A>G polymorphisms were compared in REPL and controls. FAS -1377 AA and AG
      genotypes were associated with an increased risk of REPL (OR, 3.25; 95%CI, 1.52
      6.98 and OR, 2.62; 95%CI, 1.48-4.64, respectively), whereas FAS -670 genotypes
      conferred no risk. The -1377 AA/-670 GG genotypes combination of FAS
      polymorphisms showed highest risk (OR, 8.15; 95%CI, 2.75-25.81). Genotype
      combinations -1377 GA/-670 AA and -1377 GA/-670 AG were also statistically
      significant, suggestive of their role in REPL risk.

PMID- 22386065
TI  - Hip arthroscopy and hypothermia.
AB  - PURPOSE: To determine the incidence of and factors that contribute to the
      development of hypothermia during hip arthroscopic surgery. METHODS: An analytic
      observational study was carried out in a cohort of 73 consecutive patients. All
      patients underwent hip arthroscopy for the treatment of femoroacetabular
      impingement. The patients' core temperature (esophageal) was measured throughout
      the surgery. Relevant information was collected on the patients (age, gender,
      body mass index, blood pressure) and on the procedure (volume and temperature of
      saline solution, pressure of fluid pump, surgery time, room temperature). The
      corresponding statistical analysis was performed with Stata 10.0 (StataCorp,
      College Station, TX), by use of a repeated-measures generalized estimating
      equations model. RESULTS: The patients' mean age was 33 years, and there were 39
      female and 34 male patients. The mean body mass index was 23.9; systolic blood
      pressure, 97.5 mm Hg; and diastolic blood pressure, 52.2 mm Hg. The incidence of
      hypothermia below 35 degrees C (95 degrees F) was 2.7%. The multivariate
      statistical analysis of the results showed a direct relation between hypothermia
      and surgery time of more than 120 minutes (P < .001). There was an inverse
      relation between core body temperature and surgery time (P < .001), with a drop
      of 0.19 degrees C/h (32.342 degrees F/h). Of the patients, 68.22% had a decrease
      in temperature of more than 0.5 degrees C (32.9 degrees F) until the end of
      surgery. There was also a direct relation between core body temperature and
      saline solution temperature (P < .001), body mass index (P < .01), and diastolic
      blood pressure (P < .03). CONCLUSIONS: The incidence of hypothermia below 35
      degrees C (95 degrees F) in patients who underwent hip arthroscopy for the
      treatment of femoroacetabular impingement is 2.7%. The factors that contribute
      toward the development of hypothermia during hip arthroscopic surgery are
      prolonged surgery time, low body mass index, low blood pressure during the
      procedure, and low temperature of the arthroscopic irrigation fluid.

PMID- 22386067
TI  - Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low
      antiphospholipid antibody levels.
AB  - Our objective was to determine whether there is a relationship between low
      antiphospholipid (aPL) antibody levels and the obstetrical complications of
      antiphospholipid syndrome (APS) and to analyze the impact of conventional APS
      treatment in patients with low aPL levels. To this end, we retrospectively
      reviewed the files of all patients referred to our unit (2003-2010) for
      unexplained pregnancy morbidity, with an aPL test result. We compared patients
      with APS confirmed by Sapporo criteria (Group 1) with patients with APS-like
      obstetrical complications with an aPL titer below the intermediate titer (Group
      2). Overall, 57 patients were included (25 in Group 1; 32 in Group 2).
      Obstetrical events were recurrent spontaneous abortion <10th week of gestation
      (n=9 patients in Group 1; n=13 patients in Group 2), fetal death (n=11 and 16,
      respectively), preeclampsia (n=5 in Group 1; n=6 in Group 2). The total number of
      obstetrical events per patient was very similar before APS treatment (3 [1-8] in
      Group 1; 3 [1-6] in Group 2) and decreased significantly after APS treatment to 0
      [0-2] and 0 [0-2], respectively (p<0.05). The incidence of premature births and
      the characteristics of neonates were similar in the two groups. In this study,
      treatment of patients with low aPL levels and APS-like obstetrical events was
      associated with outcomes similar to those found in otherwise normal women with
      recurrent miscarriage or other adverse events. However, properly designed
      treatment trials would be required to prove the benefit of such treatments.

PMID- 22386068
TI  - Salt intake determines retinal arteriolar structure in treatment resistant
      hypertension independent of blood pressure.
AB  - OBJECTIVE: Patients with treatment resistant hypertension are at increased risk
      of developing cardiovascular end organ damage. The role of sodium in end organ
      damage is gaining interest and an independent association of sodium and
      cardiovascular morbidity and mortality has been described. METHODS: In an
      observational study including 40 patients with treatment resistant hypertension,
      we analysed retinal arteriolar structure in vivo as a determinant of remodelling
      of small resistant vessels (wall/lumen ratio, wall thickness, wall cross section
      area) using scanning laser Doppler flowmetry and automatic full-field perfusion
      imaging analysis. Urinary sodium excretion was determined by 24 h urine sample
      and, in parallel 24 h ambulatory blood pressure was measured. We analysed the
      association of the retinal arterial structure with urinary sodium excretion and
      blood pressure. RESULTS: Wall to lumen ratio, wall thickness and wall cross
      section area were strongly associated with urinary sodium excretion but not with
      24 h blood pressure. In a multiple regression analysis including urinary sodium
      excretion, BMI, age and 24 h blood pressure, urinary sodium excretion emerged as
      the only independent determinant of wall thickness (beta=0.432, p=0.01), and wall
      cross section area (beta=0.439, p=0.008). CONCLUSION: Our results clearly
      demonstrate that salt intake influences the structure of retinal arterioles
      independent of blood pressure in treatment resistant hypertension. Considering
      the morphologic relation of retinal arteriolar and cerebral vascular structure
      these results might prove to have important implications on risk stratification
      in patients with treatment resistant hypertension.

PMID- 22386069
TI  - Assessing the effects of audiovisual semantic congruency on the perception of a
      bistable figure.
AB  - Bistable figures provide a fascinating window through which to explore human
      visual awareness. Here we demonstrate for the first time that the semantic
      context provided by a background auditory soundtrack (the voice of a young or old
      female) can modulate an observer's predominant percept while watching the
      bistable "my wife or my mother-in-law" figure (Experiment 1). The possibility of
      a response-bias account-that participants simply reported the percept that
      happened to be congruent with the soundtrack that they were listening to-was
      excluded in Experiment 2. We further demonstrate that this crossmodal semantic
      effect was additive with the manipulation of participants' visual fixation
      (Experiment 3), while it interacted with participants' voluntary attention
      (Experiment 4). These results indicate that audiovisual semantic congruency
      constrains the visual processing that gives rise to the conscious perception of
      bistable visual figures. Crossmodal semantic context therefore provides an
      important mechanism contributing to the emergence of visual awareness.

PMID- 22386070
TI  - Understanding the phase contrast optics to restore artifact-free microscopy
      images for segmentation.
AB  - Phase contrast, a noninvasive microscopy imaging technique, is widely used to
      capture time-lapse images to monitor the behavior of transparent cells without
      staining or altering them. Due to the optical principle, phase contrast
      microscopy images contain artifacts such as the halo and shade-off that hinder
      image segmentation, a critical step in automated microscopy image analysis.
      Rather than treating phase contrast microscopy images as general natural images
      and applying generic image processing techniques on them, we propose to study the
      optical properties of the phase contrast microscope to model its image formation
      process. The phase contrast imaging system can be approximated by a linear
      imaging model. Based on this model and input image properties, we formulate a
      regularized quadratic cost function to restore artifact-free phase contrast
      images that directly correspond to the specimen's optical path length. With
      artifacts removed, high quality segmentation can be achieved by simply
      thresholding the restored images. The imaging model and restoration method are
      quantitatively evaluated on microscopy image sequences with thousands of cells
      captured over several days. We also demonstrate that accurate restoration lays
      the foundation for high performance in cell detection and tracking.

PMID- 22386071
TI  - The drugs industry and peasant self-defence in a Peruvian cocaine enclave.
AB  - This article gives a detailed account of the cocaine industry and the related
      violence in the Peruvian Upper Huallaga. It is argued that in this cocaine
      producing region violence increased during state-led forced eradication
      operations of the coca plants. Most of the violent incidents were closely related
      to the diminishing cocaine industry, but they were also related to the actions of
      the state security forces. Instead of receiving support from the state's security
      apparatus, the population mobilized its own forces to fight the violence. As will
      be argued, the causes of violence in this cocaine enclave are part of a dynamic
      interaction amongst many factors - an interaction that is influenced by the local
      context, a partial state vacuum, and the social utility and the economic
      advantages of violence. One needs to be aware that motivations of those who
      engage in the violent behaviour can change over time, as underlying power
      structures are influenced by changes in local conditions. The study covers an in
      depth account of events taking place in the Upper Huallaga during the years 2003
      2007. The research material was collected by several ethnographical fieldwork
      methods.

PMID- 22386072
TI  - The use of solar energy for powering a portable autoclave.
AB  - Climate change and the depletion of fossil fuels have forced the developed world
      to look for clean energy alternatives. Solar cooking is developing in Asian and
      African countries blessed with ample sun, but is still at an early stage. A
      portable autoclave was developed in India using this technology. The Prince-40
      Concentrator provided adequate capacity to autoclave culture media and treat
      biomedical waste in a small laboratory set-up, and could save electricity worth
      Rs. 15,000 (188.10 GBP)/year or LPG worth Rs. 37,500 (470.25 GBP)/year. This
      technology would be of immense use in health centres in rural areas with frequent
      power cuts or no power supply.

PMID- 22386073
TI  - S3 - Guidelines on the treatment of psoriasis vulgaris (English version). Update.
AB  - Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The
      incidence of psoriasis in Western industrialized countries ranges from 1.5% to
      2%. Patients afflicted with severe psoriasis vulgaris may experience a
      significant reduction in quality of life. Despite the large variety of treatment
      options available, surveys have shown that patients still do not received optimal
      treatments. To optimize the treatment of psoriasis in Germany, the Deutsche
      Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen
      (BVDD) have initiated a project to develop evidence-based guidelines for the
      management of psoriasis. They were first published in 2006 and updated in 2011.
      The Guidelines focus on induction therapy in cases of mild, moderate and severe
      plaque-type psoriasis in adults including systemic therapy, UV therapy and
      topical therapies. The therapeutic recommendations were developed based on the
      results of a systematic literature search and were finalized during a consensus
      meeting using structured consensus methods (nominal group process).

PMID- 22386074
TI  - A golden anniversary: celebrating successes and establishing a vision for the
      future of the Journal of School Psychology.

PMID- 22386075
TI  - Distinguishing science from pseudoscience in school psychology: science and
      scientific thinking as safeguards against human error.
AB  - Like many domains of professional psychology, school psychology continues to
      struggle with the problem of distinguishing scientific from pseudoscientific and
      otherwise questionable clinical practices. We review evidence for the scientist
      practitioner gap in school psychology and provide a user-friendly primer on
      science and scientific thinking for school psychologists. Specifically, we (a)
      outline basic principles of scientific thinking, (b) delineate widespread
      cognitive errors that can contribute to belief in pseudoscientific practices
      within school psychology and allied professions, (c) provide a list of 10 key
      warning signs of pseudoscience, illustrated by contemporary examples from school
      psychology and allied disciplines, and (d) offer 10 user-friendly prescriptions
      designed to encourage scientific thinking among school psychology practitioners
      and researchers. We argue that scientific thinking, although fallible, is
      ultimately school psychologists' best safeguard against a host of errors in
      thinking.

PMID- 22386076
TI  - Comments on "Distinguishing science from pseudoscience in school psychology:"
      Evidence-based interventions for grandiose bragging.
AB  - The purpose of this article is to provide some perspectives on Lilienfeld,
      Ammirati, and David's (2012) paper on distinguishing science from pseudoscience
      in school psychology. In many respects their work represents an intervention for
      "grandiose bragging," a problem that has occasionally occurred when various non
      evidence-based or discredited interventions receive sensationalized positive
      endorsement for adoption in school psychology practice. In this paper, the
      implications of the Lilienfeld et al. work are discussed within the context of
      the scientist-practitioner gap, scientific thinking and evaluation of scientific
      thinking, and negative results research. The authors have advanced our thinking
      on evidence-based practices in school psychology and education.

PMID- 22386077
TI  - Statistical equating with measures of oral reading fluency.
AB  - Recent research on curriculum-based measurement of oral reading fluency has
      revealed important issues in current passage development procedures, highlighting
      how dissimilar passages are problematic for monitoring student progress. The
      purpose of this paper is to describe statistical equating as an option for
      achieving equivalent scores across non-parallel reading passages. The
      psychometric and design properties of words-correct scores are examined, and the
      requirements of traditional equating methods are discussed. Simulated and
      empirical words-correct scores are used to demonstrate the steps in the equating
      process and the situations in which each method is most appropriate.

PMID- 22386078
TI  - Teacher and observer views on student-teacher relationships: convergence across
      kindergarten and relations with student engagement.
AB  - Most studies regarding the role of teacher-child relationships for children's
      early school adjustment use only teacher ratings of relationship quality. The
      current study examines (a) the agreement between teacher and observer ratings,
      (b) whether similar patterns of relations with behavioral engagement are obtained
      across informants, and (c) which informant matters the most in the prediction of
      engagement. Teacher and observer ratings of teacher-child closeness, conflict,
      and dependency were gathered for a sample of 148 kindergartners and their
      teachers at three measurement occasions. Teacher and observer reports converged
      to a moderate degree but only when considering multiple occasions and ruling out
      occasion-specific variance. Although some relations with behavioral engagement
      were similar, only teacher ratings had unique, added value in this prediction.

PMID- 22386079
TI  - Do girls and boys perceive themselves as equally engaged in school? The results
      of an international study from 12 countries.
AB  - This study examined gender differences in student engagement and academic
      performance in school. Participants included 3420 students (7th, 8th, and 9th
      graders) from Austria, Canada, China, Cyprus, Estonia, Greece, Malta, Portugal,
      Romania, South Korea, the United Kingdom, and the United States. The results
      indicated that, compared to boys, girls reported higher levels of engagement in
      school and were rated higher by their teachers in academic performance. Student
      engagement accounted for gender differences in academic performance, but gender
      did not moderate the associations among student engagement, academic performance,
      or contextual supports. Analysis of multiple-group structural equation modeling
      revealed that perceptions of teacher support and parent support, but not peer
      support, were related indirectly to academic performance through student
      engagement. This partial mediation model was invariant across gender. The
      findings from this study enhance the understanding about the contextual and
      personal factors associated with girls' and boys' academic performance around the
      world.

PMID- 22386080
TI  - Teacher practices as predictors of children's classroom social preference.
AB  - Students who do not get along with their peers are at elevated risk for academic
      disengagement and school failure. Research has predominantly focused on factors
      within such children that contribute to their peer problems. This study considers
      whether teacher practices also predict social preference for children in that
      classroom. Participants were 26 elementary school teachers and 490 students in
      their classrooms followed for one school year. Results suggested that teachers
      who favored the most academically talented students in the fall had classrooms
      where children had lower average social preference in the spring after
      statistical control of children's fall social preference and externalizing
      behavior problems. Teachers who demonstrated emotionally supportive relationships
      with students in the fall had classrooms where children had greater possibility
      of changing their social preference from fall to spring. Although children with
      high externalizing behaviors tended to experience declining social preference
      over the course of the school year, teachers' learner-centered practices
      attenuated this progression. However, teachers' favoring of the most academically
      talented accentuated the negative relation between externalizing behaviors and
      social preference. Implications for school psychology practitioners are
      discussed.

PMID- 22386081
TI  - The effects of Wechsler Intelligence Scale for Children-Fourth Edition cognitive
      abilities on math achievement.
AB  - This study used structural equation modeling to examine the effect of Stratum III
      (i.e., general intelligence) and Stratum II (i.e., Comprehension-Knowledge, Fluid
      Reasoning, Short-Term Memory, Processing Speed, and Visual Processing) factors of
      the Cattell-Horn-Carroll (CHC) cognitive abilities, as operationalized by the
      Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV; Wechsler,
      2003a) subtests, on Quantitative Knowledge, as operationalized by the Wechsler
      Individual Achievement Test, Second Edition (WIAT-II; Wechsler, 2002) subtests.
      Participants came from the WISC-IV/WIAT-II linking sample (n=550). We compared
      models that predicted Quantitative Knowledge using only Stratum III factors, only
      Stratum II factors, and both Stratum III and Stratum II factors. Results
      indicated that the model with only the Stratum III factor predicting Quantitative
      Knowledge best fit the data.

PMID- 22386082
TI  - Teacher- and school-level predictors of teacher efficacy and burnout: identifying
      potential areas for support.
AB  - Although several studies relate low teacher efficacy and high burnout to the
      quality of instruction and students' academic achievement, there has been limited
      research examining factors that predict teacher efficacy and burnout. The current
      study employed a longitudinal, multilevel modeling approach to examine the
      influence of teacher- and school-level factors on the development of both teacher
      efficacy and burnout. Data were collected 3 times across 2 academic years from
      600 teachers at 31 elementary schools. The results indicated that both teacher
      efficacy and burnout increased over time. Teacher preparedness and perceptions of
      teacher affiliation and leadership were significantly associated with both the
      intercept and growth of teacher efficacy and burnout; however, school-level
      factors were generally unrelated to both outcomes. Implications for screenings
      and teacher-targeted interventions are discussed.

PMID- 22386083
TI  - Nitrogen removal in a single-chamber microbial fuel cell with nitrifying biofilm
      enriched at the air cathode.
AB  - Nitrogen removal is needed in microbial fuel cells (MFCs) for the treatment of
      most waste streams. Current designs couple biological denitrification with side
      stream or combined nitrification sustained by upstream or direct aeration, which
      negates some of the energy-saving benefits of MFC technology. To achieve
      simultaneous nitrification and denitrification, without extra energy input for
      aeration, the air cathode of a single-chamber MFC was pre-enriched with a
      nitrifying biofilm. Diethylamine-functionalized polymer (DEA) was used as the Pt
      catalyst binder on the cathode to improve the differential nitrifying biofilm
      establishment. With pre-enriched nitrifying biofilm, MFCs with the DEA binder had
      an ammonia removal efficiency of up to 96.8% and a maximum power density of 900
      +/- 25 mW/m(2), compared to 90.7% and 945 +/- 42 mW/m(2) with a Nafion binder. A
      control with Nafion that lacked nitrifier pre-enrichment removed less ammonia and
      had lower power production (54.5% initially, 750 mW/m(2)). The nitrifying biofilm
      MFCs had lower Coulombic efficiencies (up to 27%) than the control reactor (up to
      36%). The maximum total nitrogen removal efficiency reached 93.9% for MFCs with
      the DEA binder. The DEA binder accelerated nitrifier biofilm enrichment on the
      cathode, and enhanced system stability. These results demonstrated that with
      proper cathode pre-enrichment it is possible to simultaneously remove organics
      and ammonia in a single-chamber MFC without supplemental aeration.

PMID- 22386084
TI  - Continuous-flow solar UVB disinfection reactor for drinking water.
AB  - Access to safe, reliable sources of drinking water is a long-standing problem
      among people in developing countries. Sustainable solutions to these problems
      often involve point-of-use or community-scale water treatment systems that rely
      on locally-available resources and expertise. This philosophy was used in the
      development of a continuous-flow, solar UVB disinfection system. Numerical
      modeling of solar UVB spectral irradiance was used to define temporal variations
      in spectral irradiance at several geographically-distinct locations. The results
      of these simulations indicated that a solar UVB system would benefit from
      incorporation of a device to amplify ambient UVB fluence rate. A compound
      parabolic collector (CPC) was selected for this purpose. Design of the CPC was
      based on numerical simulations that accounted for the shape of the collector and
      reflectance. Based on these simulations, a prototype CPC was constructed using
      materials that would be available and inexpensive in many developing countries. A
      UVB-transparent pipe was positioned in the focal area of the CPC; water was
      pumped through the pipe to allow exposure of waterborne microbes to germicidal
      solar UVB radiation. The system was demonstrated to be effective for inactivation
      of Escherichia coli, and DNA-weighted UV dose was shown to govern reactor
      performance. The design of the reactor is expected to scale linearly, and
      improvements in process performance (relative to results from the prototype) can
      be expected by use of larger CPC geometry, inclusion of better reflective
      materials, and application in areas with greater ambient solar UV spectral
      irradiance than the location of the prototype tests. The system is expected to
      have application for water treatment among communities in (developing) countries
      in near-equatorial and tropical locations. It may also have application for
      disaster relief or military field operations, as well as in water treatment in
      areas of developed countries that receive relatively intense solar UVB radiation.

PMID- 22386085
TI  - Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: operator and
      institutional requirements for transcatheter valve repair and replacement, Part
      1: transcatheter aortic valve replacement.

PMID- 22386086
TI  - Nonintubated needlescopic video-assisted thoracic surgery for management of
      peripheral lung nodules.
AB  - BACKGROUND: Video-assisted thoracic operations are usually performed with 5-mm or
      10-mm instruments under general anesthesia with single-lung ventilation.
      Management of peripheral lung nodules by a needlescopic video-assisted
      thoracoscopic operation, without endotracheal intubation, has rarely been
      attempted. We evaluated the feasibility and safety of this minimally invasive
      technique in managing peripheral lung nodules. METHODS: From August 2009 through
      March 2011, 46 patients with peripheral lung nodules were treated using 3-mm
      needlescopic video-assisted thoracoscopic operations for wedge resection with
      epidural anesthesia and sedation, without endotracheal intubation. RESULTS: A
      definitive diagnosis was obtained in all 46. Extension of the 3-mm incisions was
      required in 8 patients because of primary lung cancer requiring a lobectomy in 3,
      pleural adhesions in 3, and difficulty in identifying or resecting the nodule in
      2. Two patients required conversion to intubated single-lung ventilation because
      of dense adhesions between the lungs and the diaphragm. Operations lasted a mean
      of 69.2 +/- 46.8 minutes. Postoperative side effects occurred in 4 patients,
      including sore throat, headache, and vomiting requiring medication. Operative
      complications developed in 1 patient who had air leaks for more than 3 days
      postoperatively. The mean postoperative chest tube drainage and hospital stay
      were 1.1 days and 2.7 days, respectively. Postoperative neuralgia was noted in 12
      patients (26%). Most patients (74%) were very satisfied or satisfied with the
      resulting scars. CONCLUSIONS: Nonintubated needlescopic video-assisted
      thoracoscopic operations are technically feasible and safe and may be a less
      invasive alternative in the management of selected patients with peripheral
      pulmonary nodules.

PMID- 22386087
TI  - Thoracic surgery in the real world: does surgical specialty affect outcomes in
      patients having general thoracic operations?
AB  - BACKGROUND: Most general thoracic operations in the United States are performed
      by general surgeons. Results obtained by those identified as general surgeons are
      often compared with those identified as thoracic surgeons. METHODS: We
      interrogated the American College of Surgeons National Surgical Quality
      Improvement Project database over a 5-year period to compare outcomes in patients
      who underwent similar operations by surgeons identified as either thoracic
      surgeons or general surgeons. We employed propensity-score matching to minimize
      confounding when estimating the effect of surgeon identity on postoperative
      outcomes. RESULTS: During the study period, thoracic surgeons performed 3,263
      major pulmonary or esophageal operations, and general surgeons performed 15,057
      similar operations. Compared with patients operated on by general surgeons,
      patients operated on by thoracic surgeons had significant excess multivariate
      comorbidities, including insulin-dependent diabetes mellitus, chronic obstructive
      pulmonary disease, concurrent pneumonia, congestive heart failure, previous
      cardiac surgery, dialysis-dependent renal failure, disseminated cancer, prior
      sepsis, and previous operation within 30 days. Likewise, patients in highest risk
      categories had operations performed by thoracic surgeons more commonly than by
      general surgeons. Unadjusted comparisons for mortality and serious morbidity
      showed significantly worse mortality and pulmonary complications in patients
      operated on by thoracic surgeons. However, with propensity matching according to
      surgeon type, thoracic surgeons had significantly fewer serious adverse outcomes
      compared with general surgeons, and this decreased morbidity occurred in a higher
      risk cohort. CONCLUSIONS: Our results show that patients operated on by thoracic
      surgeons have higher acuity compared with patients operated on by general
      surgeons. When patients are matched for comorbidities and serious preoperative
      risk factors, thoracic surgeons have improved outcomes, especially with regard to
      infectious complications and composite morbidity.

PMID- 22386088
TI  - Completion pericardiectomy for recurrent constrictive pericarditis: importance of
      timing of recurrence on late clinical outcome of operation.
AB  - BACKGROUND: Recurrent right-side heart failure after operation for constrictive
      pericarditis (CP) may be caused by incomplete pericardiectomy, recurrent
      constriction due to exuberant scar tissue, or diastolic dysfunction. Because the
      risks and benefits of reoperation are not well defined, we reviewed the outcome
      of completion pericardiectomy. METHODS: From 1993 to December 2010, 41 patients
      underwent redo pericardiectomy. Thirty-eight patients had the initial operation
      elsewhere, and 3 had first pericardiectomy at our clinic. All patients had the
      diagnosis of CP at initial operation. We divided patients into two groups
      according to the interval between the first and second pericardiectomies: group
      A, 1 year or less, n = 20; group B, more than 1 year, n = 21. RESULTS: The mean
      age was 57.6 +/- 12.7 years, and there were 34 males (83%). Twenty-six patients
      (63%) were in New York Heart Association class II, 10 (24%) were in class III,
      and 5 (12%) were in class IV. Etiologies were idiopathic in 20 (49%), prior
      cardiac surgery in 13 (32%), radiation in 6 (15%), and trauma in 2 (5%). There
      was no significant difference in patient characteristics between group A and
      group B. The 30-day and in-hospital mortalities were 7% (n = 3) and 12% (n = 5),
      respectively. Overall 5-year survival was 49%, and was significantly better in
      group A than group B (73% versus 29%, p = 0.032). In multivariate analysis, New
      York Heart Association class III or IV and the interval between operations longer
      than 1 year were significant risk factors for death (p = 0.010 and p = 0.027,
      respectively). CONCLUSIONS: The significant early mortality of repeat
      pericardiectomy emphasizes the importance of complete pericardial resection at
      first operation and accurate diagnosis of recurrent constriction. The poor
      clinical outcome of late (more than 1 year) reoperation suggests that many of
      these patients may have unrecognized diastolic dysfunction or recurrent
      mediastinal scarring as the cause of right-side heart failure rather than
      incomplete initial pericardiectomy.

PMID- 22386089
TI  - A novel tracheobronchial reconstruction for right upper lung carcinoma involving
      the lower trachea: preliminary results.
AB  - BACKGROUND: We developed a novel technique for tracheobronchial reconstruction
      after resection of carcinoma of the right upper lung involving the right main
      bronchus and lower trachea. Preliminary results of the technique are reported.
      METHODS: Between December 2007 and October 2011, 9 patients underwent treatment
      with our new technique. The right upper lobe was resected together with the
      involved right main bronchus and right lateral wall of the lower trachea. Closure
      of the trachea was started at the level of the carina and continued upward,
      leaving an oval opening at the upper end of the tracheal defect, to which the
      bronchus intermedius was reimplanted. The sutured lower trachea became the
      extension of the left main bronchus. RESULTS: The procedure was completed
      successfully in all 9 patients. Two patients underwent partial carinal resection,
      2 underwent replacement of the superior vena cava by interposition graft, 2
      underwent partial resection of the superior vena cava, and 1 underwent partial
      resection of the esophageal wall. There were no perioperative deaths. No major
      complications, including dehiscence, stenosis, and adult respiratory distress
      syndrome, were observed. Arrhythmia occurred in 2 patients, and vocal cord
      paresis and pneumonia occurred in 1 patient. One patient died 31 months after
      operation, and 1 patient was lost to follow-up 28 months after operation, without
      tumor recurrence. The other 7 are alive to date. CONCLUSIONS: Despite this being
      a small series and short follow-up, this tracheobronchial reconstruction shows
      encouraging preliminary results with low mortality and morbidity, and could be an
      alternative to other methods for the treatment of carefully selected patients
      with advanced carcinoma of the right upper lobe.

PMID- 22386090
TI  - Results of long-term follow-up of patients with completely resected non-small
      cell lung cancer.
AB  - BACKGROUND: In patients with completely resected non-small cell lung cancer,
      recurrence-free survival, postrecurrence survival, and metachronous primary lung
      cancer have not been well studied at the same time. METHODS: A total of 315
      patients with non-small cell lung cancer who underwent complete resection between
      2001 and 2005 were examined. Patients were routinely assessed with computed
      tomography of the chest and physical checkups every 4 months for the first 2
      years and every 6 months from the third to the fifth year. After that, they were
      examined annually. RESULTS: The overall 5-year survival was 70%. Of all 315
      patients, 107 had recurrent disease. The median recurrence-free survival was 15.7
      months. Multivariate analysis showed that pathologic stage and pleural invasion
      were associated with decreased recurrence-free survival. The median
      postrecurrence survival was 18.7 months. Multivariate analysis indicated that
      male sex, pleural invasion, extrathoracic recurrence, and supportive care for
      recurrence were associated with decreased postrecurrence survival. The cumulative
      rate of metachronous primary lung cancer at 5 years was 3.7%, and it developed
      even 8 years after the initial operation. CONCLUSIONS: Only pleural invasion of
      the original lung cancer was related to both recurrence-free survival and
      postrecurrence survival. Moreover, postrecurrence survival was related to both
      site and treatment of the initial recurrence. The incidence of metachronous
      primary lung cancer was stable over time after the initial operation.

PMID- 22386091
TI  - Thoracoscopic lobectomy and segmentectomy for infectious lung disease.
AB  - BACKGROUND: The potential benefits of thoracoscopic lobectomy and segmentectomy
      for early stage non-small cell lung cancer have been well documented in the
      literature. However, little is known about the use of these techniques in
      patients requiring resection for infectious or inflammatory lung disease.
      METHODS: Using a prospectively collected database, we performed a retrospective
      review of consecutive operations from July 2004 to June 2010. All patients who
      underwent elective thoracoscopic lobectomy or segmentectomy for focal
      bronchiectasis or cavitary lung disease associated with active pulmonary
      infection were included. RESULTS: In all, 212 resections were performed in 171
      patients. The average age was 59 years (range, 26 to 82 years). Patients were
      predominately white (93%) and female (93%). Indications for surgery included
      recurrent active infection, hemoptysis, or antibiotic intolerance associated with
      focal bronchiectasis (86%), cavitary disease (7%), or both (7%). Operations
      included 126 lobectomies, 73 segmentectomies, 10 lobe plus segmental resections,
      and 3 bilobectomies. Conversion to thoracotomy occurred in 10 patients. The
      operative mortality rate was zero. Complications occurred in 9%, consisting
      largely of prolonged air leak and atrial fibrillation. The mean hospital length
      of stay was 3.7 days. CONCLUSIONS: Thoracoscopic lobectomy and segmentectomy for
      individuals with infectious lung disease can be accomplished safely with minimal
      morbidity and mortality. These techniques may provide the optimal surgical
      approach for patients with focal bronchiectasis or cavitary lung disease
      requiring resection.

PMID- 22386092
TI  - Assembling and maintaining the Photosystem II complex in chloroplasts and
      cyanobacteria.
AB  - Plants, algae and cyanobacteria grow because of their ability to use sunlight to
      extract electrons from water. This vital reaction is catalysed by the Photosystem
      II (PSII) complex, a large multi-subunit pigment-protein complex embedded in the
      thylakoid membrane. Recent results show that assembly of PSII occurs in a step
      wise fashion in defined regions of the membrane system, involves conserved
      auxiliary factors and is closely coupled to chlorophyll biosynthesis. PSII is
      also repaired following damage by light. FtsH proteases play an important role in
      selectively removing damaged proteins from the complex, both in chloroplasts and
      cyanobacteria, whilst undamaged subunits and pigments are recycled. The
      chloroplastic Deg proteases play a supplementary role in PSII repair.

PMID- 22386094
TI  - Part 19: What is a P value?
AB  - This review represents a nontechnical explanation of P values intended for the
      statistical novice.

PMID- 22386095
TI  - Is it really a STEMI or Takotsubo cardiomyopathy?
AB  - The goal of this column is to provide a case that is pertinent to the medical
      transport industry and provides teaching points for crewmembers who are actively
      involved in out-of-hospital transport, whether by air or by other means. In this
      issue, we have the opportunity to examine two similar cases from a single crew
      (nurse/paramedic) that occurred within several months of each other and to
      describe a moderately rare condition that mimics a common diagnosis encountered
      by critical care personnel.

PMID- 22386096
TI  - Tattoo you.

PMID- 22386098
TI  - Voices in our heads: self-inflicted pressure.

PMID- 22386099
TI  - Strategies to reduce US HEMS accidents.

PMID- 22386100
TI  - Bag valve mask failure during HEMS intubated stretcher winch.
AB  - An intubated prehospital trauma patient was undergoing bag valve mask (BVM)
      ventilation during a stretcher winch in an AW 139 helicopter. On approach to
      approximately 50 feet under the rotor disc, the bag valve mask failed, with no
      adverse outcome. External pressure obstructing reinflation from rotor downwash
      was thought to be the cause. We tested two BVMs with differing compliances under
      similar conditions in a manikin model and found the original, more compliant BVM
      failed again. The stiffer, less compliant BVM did not fail. This has led to a
      change in the type of BVM used for helicopter emergency medical services (HEMS)
      in our service.

PMID- 22386101
TI  - Helicopter rescue involving the winching of a physician.
AB  - INTRODUCTION: We sought to study the operational and medical aspects of
      helicopter rescue missions involving the use of a winch. SETTING: A single
      helicopter-based medical service of a pre-alpine region of Switzerland. METHODS:
      We prospectively studied consecutive primary rescue interventions involving
      winching of a physician, from October 1, 1998 to October 1, 2002. Demographic,
      medical and operational aspects as well as outcome at 48 hours were analyzed.
      RESULTS: We included 133 patients. Most (74%) were male, with traumatic injuries
      (77%). The median scene time of the nine severely injured patients (Injury
      Severity Scale [ISS] > 15) was significantly longer compared with the other
      patients (54 vs 37 minutes; P < .05). The main medical procedures performed were
      orotracheal intubation (n = 5), fracture reductions (n = 5), major analgesia with
      sedation (n = 4), and intravenous fluid administration of more than 1,500 mL (n =
      4). Fourteen (10%) patients suffering from minor injuries were triaged by the
      physician and not airlifted to the hospital. All 133 patients were alive at 48
      hours. Sixty-nine (52%) were still hospitalized. No secondary interhospital
      transfer was required. CONCLUSION: Our study provides a better knowledge of
      injury profile, medical aspects, and outcomes of patients rescued necessitating a
      winching procedure.

PMID- 22386102
TI  - K-plan for patient repatriation after mass casualty events abroad.
AB  - In addition to requests for individual aeromedical evacuation (AE), medical
      assistance companies also may respond to mass casualty incidents abroad. The
      purpose of this report was to evaluate the effectiveness of our primary casualty
      plan, based on experience involving a January 2010 bus crash in southern Egypt.
      The main evaluative criterion was time elapsed from the initial call until the
      return of victims to their home country. Three critically injured patients
      underwent an initial AE to Cairo for advanced trauma care. After stabilization,
      they arrived back in their home country 42 hours after the initial call. The
      remaining group of patients arrived 27 hours later, or a total of 69 hours after
      the first call. These findings suggest that the "K-Plan" standardized operating
      process may be effective for rapid and appropriate repatriation of numerous
      victims. Some specific issues, such as efficiently locating a large-capacity
      charter aircraft, require further improvement.

PMID- 22386104
TI  - [Determinants of the intention of post-secondary students to eat at least five
      servings of vegetables and fruit daily].
AB  - BACKGROUND: Vegetable and fruit consumption helps reduce the occurrence of
      overweight, obesity, and other chronic diseases. However, only 50% of young
      adults eat at least five servings of these foods daily. Based on the construct of
      the Theory of planned behaviour of Ajzen (1991) to which other constructs were
      added (descriptive norm, perceived regularity of the behaviour and past
      behaviour), this study aims at identifying the determinants in the intention of
      young adults in postsecondary education institutions to eat at least five
      servings of vegetables and fruit daily during the next three months. METHODS: A
      sample of 385 students in two CEGEP (junior college institutions) in the Quebec
      City area participated in this correlation study on a volunteer basis. While
      attending class, they completed a self-administered questionnaire. RESULTS:
      Hierarchical regression analyses showed that perceived behavioural controls and
      the perceived weight of facilitating factors and barriers to the behaviour,
      explained 75% of the intention variance. Another 4% was explained when the
      perceived regularity of the behaviour, the descriptive norm, and past-behaviour,
      were added to the analysis. Logistic regression analyses show that individuals
      presenting weak/strong intention can be differentiated among themselves as to the
      perception of benefits derived from a daily consumption of vegetables and fruit
      (such as maintaining good health, eating foods that taste good), and as to
      facilitating factors/barriers that assist or inhibit such consumption (possessing
      more information on the nutritional value and taste of vegetables and fruit, or
      disposing of sufficient time to prepare them). CONCLUSION: To our knowledge, this
      is the first study done in Quebec using a recognized theoretical model to
      identify the determinants of the intention to eat at least five servings of
      vegetables and fruit daily in a sample of young adults in postsecondary education
      institutions. The results may be helpful in designing the contents of
      interventions aimed at maintaining and increasing daily consumption of vegetables
      and fruit by young adults.

PMID- 22386105
TI  - The mechanical behavior of PMMA/bone specimens extracted from augmented
      vertebrae: a numerical study of interface properties, PMMA shrinkage and
      trabecular bone damage.
AB  - Recently published compression tests on PMMA/bone specimens extracted after
      vertebral bone augmentation indicated that PMMA/bone composites were not
      reinforced by the trabecular bone at all. In this study, the reasons for this
      unexpected behavior should be investigated by using non-linear micro-FE models.
      Six human vertebral bodies were augmented with either standard or low-modulus
      PMMA cement and scanned with a HR-pQCT system before and after augmentation. Six
      cylindrical PMMA/bone specimens were extracted from the augmented region, scanned
      with a micro-CT system and tested in compression. Four different micro-FE models
      were generated from these images which showed different bone tissue material
      behavior (with/without damage), interface behavior (perfect bonding, frictionless
      contact) and PMMA shrinkage due to polymerization. The non-linear stress-strain
      curves were compared between the different micro-FE models as well as to the
      compression tests of the PMMA/bone specimens. Micro-FE models with contact
      between bone and cement were 20% more compliant compared to those with perfect
      bonding. PMMA shrinkage damaged the trabecular bone already before mechanical
      loading, which further reduced the initial stiffness by 24%. Progressing bone
      damage during compression dominated the non-linear part of the stress-strain
      curves. The micro-FE models including bone damage and PMMA shrinkage were in good
      agreement with the compression tests. The results were similar with both cements.
      In conclusion, the PMMA/bone interface properties as well as the initial bone
      damage due to PMMA polymerization shrinkage clearly affected the stress-strain
      behavior of the composite and explained why trabecular bone did not contribute to
      the stiffness and strength of augmented bone.

PMID- 22386106
TI  - Simulation of lower limb axial arterial length change during locomotion.
AB  - The effect of external forces on axial arterial wall mechanics has conventionally
      been regarded as secondary to hemodynamic influences. However, arteries are
      similar to muscles in terms of the manner in which they traverse joints, and
      their three-dimensional geometrical requirements for joint motion. This study
      considers axial arterial shortening and elongation due to motion of the lower
      extremity during gait, ascending stairs, and sitting-to-standing motion. Arterial
      length change was simulated by means of a graphics based anatomic and kinematic
      model of the lower extremity. This model estimated the axial shortening to be as
      much as 23% for the femoropopliteal arterial region and as much as 21% for the
      iliac artery. A strong correlation was observed between femoropopliteal artery
      shortening and maximum knee flexion angle (r2=0.8) as well as iliac artery
      shortening and maximum hip angle flexion (r2=0.9). This implies a significant
      mechanical influence of locomotion on arterial behavior in addition to
      hemodynamics factors. Vascular tissue has high demands for axial compliance that
      should be considered in the pathology of atherosclerosis and the design of
      vascular implants.

PMID- 22386107
TI  - Injectable calcium phosphate cement for augmentation around cancellous bone
      screws. In vivo biomechanical studies.
AB  - In lower cancellous apparent bone density, it can be difficult to achieve
      adequate screw fixation and hence stable fracture fixation. Different strategies
      have been proposed, one of them is through augmentation using calcium phosphate
      cement in the region at or close to the screw thread itself. To support the
      hypothesis of an improved screw fixation technique by augmentation of the bone
      surrounding the implanted screw, in vivo biomechanical and densitometric studies
      are performed on rabbit specimen where normal and simulated weak bone quality are
      considered. In particular, the evolution of screw stability till 12 weeks
      following the implantation is quantified. A statistical significance in the pull
      out force for augmented versus non-augmented screws was found for the shorter
      time periods tested of <= 5 days whilst the pull out force was found to increase
      with time for both augmented and non-augmented screws during the 12 week course
      of the study. The results of the study demonstrate that the use of an injectable
      calcium phosphate cement which sets in vivo can significantly improve screw pull
      out strength at and after implantation for normal and simulated weak bone
      quality.

PMID- 22386108
TI  - Mercury capture into biogenic amorphous selenium nanospheres produced by mercury
      resistant Shewanella putrefaciens 200.
AB  - Shewanella putrefaciens 200, resistant to high concentration of Hg(II), was
      selected for co-removal of mercury and selenium from aqueous medium. Biogenic
      Hg(0) reduced from Hg(II) by S. putrefaciens 200 was captured into extracellular
      amorphous selenium nanospheres, resulting in the formation of stable HgSe
      nanoparticles. This bacterial reduction could be a new strategy for mercury
      removal from aquatic environments without secondary pollution of mercury
      methylation or Hg(0) volatilization.

PMID- 22386109
TI  - Thiourea leaching gold and silver from the printed circuit boards of waste mobile
      phones.
AB  - The present communication deals with the leaching of gold and silver from the
      printed circuit boards (PCBs) of waste mobile phones using an effective and less
      hazardous system, i.e., a thiourea leaching process as an alternative to the
      conventional and toxic cyanide leaching of gold. The influence of particle size,
      thiourea and Fe(3+) concentrations and temperature on the leaching of gold and
      silver from waste mobile phones was investigated. Gold extraction was found to be
      enhanced in a PCBs particle size of 100 mesh with the solutions containing 24 g/L
      thiourea and Fe(3+) concentration of 0.6% under the room temperature. In this
      case, about 90% of gold and 50% of silver were leached by the reaction of 2h. The
      obtained data will be useful for the development of processes for the recycling
      of gold and silver from the PCBs of waste mobile phones.

PMID- 22386110
TI  - [Somatomorphic syndrome: Proposed concepts and practices].

PMID- 22386111
TI  - [Primary pure squamous cell carcinoma of the gallbladder revealed by an acute
      angiocholitis].

PMID- 22386112
TI  - Transmastoid approach to temporal bone cerebrospinal fluid leaks.
AB  - PURPOSE: The aim of the study was to evaluate various presentations and treatment
      options for spontaneous cerebrospinal fluid (CSF) leakage originating in the
      temporal bone. MATERIALS AND METHODS: Clinical data and imaging results for 18
      ears (15 patients) presenting with spontaneous CSF leakage originating in the
      temporal bone were reviewed. Average follow-up period was 13.5 months. The main
      outcome measure was presence of persistent CSF leak postoperatively. A standard
      postauricular mastoidectomy was performed. RESULTS: Fifteen patients diagnosed
      with spontaneous CSF leakage over an 8-year period including 3 treated for
      bilateral disease were included in the study. The age ranged between 33 and 83
      years. Presenting symptoms included serous otitis media (44%), persistent
      otorrhea after tympanostomy tube placement (28%), and meningitis (28%).
      Preoperative diagnosis was made using imaging studies and was substantiated by
      observation of CSF leakage and dural herniation intraoperatively. Treatment was
      eustachian tube plugging (5%), mastoidectomy with fat obliteration (61%), middle
      fossa approach with extradural (17%), intradural repair (5%), or combined middle
      fossa and transmastoid (TM) approach (11%). Successful treatment was obtained in
      17 of the 18 cases. The last 9 patients in the series underwent TM approach alone
      for repair with no treatment failures. CONCLUSIONS: Repair of defects in tegmen
      mastoideum and posterior fossa can be successfully achieved on an outpatient
      basis without regard to size and multitude of defects via TM approach. This
      approach obviates the need for a craniotomy or lumbar drain.

PMID- 22386113
TI  - [Intravesical protrusion of retropubic osteophyte mimicking an urinary bladder
      tumour].

PMID- 22386114
TI  - [Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU
      guidelines].
AB  - CONTEXT: New data regarding treatment of muscle-invasive and metastatic bladder
      cancer (MiM-BC) has emerged and led to an update of the European Association of
      Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines
      for MiM-BC with a specific focus on treatment. EVIDENCE ACQUISITION: New
      literature published since the last update of the EAU guidelines in 2008 was
      obtained from Medline, the Cochrane Database of Systematic Reviews, and reference
      lists in publications and review articles and comprehensively screened by a group
      of urologists, oncologists, and a radiologist appointed by the EAU Guidelines
      Office. Previous recommendations based on the older literature on this subject
      were also taken into account. Levels of evidence (LEs) and grades of
      recommendations (GRs) were added based on a system modified from the Oxford
      Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS:
      Current data demonstrate that neoadjuvant chemotherapy in conjunction with
      radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC
      remains the basic treatment of choice in localised invasive disease for both
      sexes. An attempt has been made to define the extent of surgery under standard
      conditions in both sexes. An orthotopic bladder substitute should be offered to
      both male and female patients lacking any contraindications, such as no tumour at
      the level of urethral dissection. In contrast to neoadjuvant chemotherapy,
      current advice recommends the use of adjuvant chemotherapy only within clinical
      trials. Multimodality bladder-preserving treatment in localised disease is
      currently regarded only as an alternative in selected, well-informed, and
      compliant patients for whom cystectomy is not considered for medical or personal
      reasons. In metastatic disease, the first-line treatment for patients fit enough
      to sustain cisplatin remains cisplatin-containing combination chemotherapy. With
      the advent of vinflunine, second-line chemotherapy has become available.
      CONCLUSIONS: In the treatment of localised invasive bladder cancer (BCa), the
      standard treatment remains radical surgical removal of the bladder within
      standard limits, including as-yet-unspecified regional lymph nodes. However, the
      addition of neoadjuvant chemotherapy must be considered for certain specific
      patient groups. A new drug for second-line chemotherapy (vinflunine) in
      metastatic disease has been approved and is recommended.

PMID- 22386115
TI  - [EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the
      2011 update].
AB  - CONTEXT AND OBJECTIVE: To present the 2011 European Association of Urology (EAU)
      guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION:
      Literature published between 2004 and 2010 on the diagnosis and treatment of
      NMIBC was systematically reviewed. Previous guidelines were updated, and the
      level of evidence and grade of recommendation were assigned. EVIDENCE SYNTHESIS:
      Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC.
      Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained
      by transurethral resection (TUR) in papillary tumours or by multiple bladder
      biopsies in CIS. In papillary lesions, a complete TUR is essential for the
      patient's prognosis. Where the initial resection is incomplete or where a high
      grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk.
      In papillary tumours, the risks of both recurrence and progression may be
      estimated for individual patients using the scoring system and risk tables. The
      stratification of patients into low-, intermediate-, and high-risk groups
      (separately for recurrence and progression) is pivotal to recommending adjuvant
      treatment. For patients with a low risk of tumour recurrence and progression, one
      immediate instillation of chemotherapy is recommended. Patients with an
      intermediate or high risk of recurrence and an intermediate risk of progression
      should receive one immediate instillation of chemotherapy followed by a minimum
      of 1 yr of bacillus Calmette-Guerin (BCG) intravesical immunotherapy or further
      instillations of chemotherapy. Papillary tumours with a high risk of progression
      and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to
      the highest risk patients, and it is at least recommended in BCG failure
      patients. CONCLUSIONS: These abridged EAU guidelines present updated information
      on the diagnosis and treatment of NMIBC for incorporation into clinical practice.

PMID- 22386116
TI  - In this issue, we present four papers that have been chosen by Tony Herndon on
      prenatal aspects of Paediatric Urology, together with his editorial commentary.
      Introduction.

PMID- 22386117
TI  - Commentary to 'short-term outcome of mild isolated antenatal hydronephrosis
      conservatively managed'.

PMID- 22386118
TI  - Reducing developmental risk for emotional/behavioral problems: a randomized
      controlled trial examining the Tools for Getting Along curriculum.
AB  - Researchers have demonstrated that cognitive-behavioral intervention strategies -
      such as social problem solving - provided in school settings can help ameliorate
      the developmental risk for emotional and behavioral difficulties. In this study,
      we report the results of a randomized controlled trial of Tools for Getting Along
      (TFGA), a social problem-solving universally delivered curriculum designed to
      reduce the developmental risk for serious emotional or behavioral problems among
      upper elementary grade students. We analyzed pre-intervention and post
      intervention teacher-report and student self-report data from 14 schools, 87
      classrooms, and a total of 1296 students using multilevel modeling. Results
      (effect sizes calculated using Hedges' g) indicated that students who were taught
      TFGA had a more positive approach to problem solving (g=.11) and a more rational
      problem-solving style (g=.16). Treated students with relatively poor baseline
      scores benefited from TFGA on (a) problem-solving knowledge (g=1.54); (b) teacher
      rated executive functioning (g=.35 for Behavior Regulation and .32 for
      Metacognition), and proactive aggression (g=.20); and (c) self-reported trait
      anger (g=.17) and anger expression (g=.21). Thus, TFGA may reduce risk for
      emotional and behavioral difficulties by improving students' cognitive and
      emotional self-regulation and increasing their pro-social choices.

PMID- 22386119
TI  - Exploring the associations between coping patterns for everyday stressors and
      mental health in young schoolchildren.
AB  - The purposes of this study were to explore the structure of coping with everyday
      stressors in a young nonclinical population and examine the relationship between
      coping and mental health. A total of 1324 children from 91 second-grade classes
      in 35 schools participated. Mental health was assessed using the parent and
      teacher forms of the Strengths and Difficulties Questionnaire (Goodman, 1997),
      and coping was assessed by the Kidcope (Spirito et al., 1988) self-report
      checklist. Exploratory and confirmatory factor analyses suggested a three-factor
      structure of coping. Latent-variable regression analysis indicated that coping
      categories including both active and emotional strategies were associated with
      fewer mental health problems, whereas withdrawal and oppositional coping
      strategies were associated with greater mental health problems. With some
      important exceptions, the results replicated previous studies of adults and
      adolescents. The need for new, more comprehensive coping assessments is
      highlighted.

PMID- 22386120
TI  - Links between local language competence and peer relations among Swiss and
      immigrant children: the mediating role of social behavior.
AB  - The primary aim of this investigation was to evaluate a model in which children's
      social behaviors, including prosocial behavior, setting limits, and social
      withdrawal, were hypothesized to mediate the links between local language
      competence (LLC) and peer acceptance and victimization. Longitudinal data were
      collected via teacher and peer reports on 541 (286 boys and 255 girls) immigrant
      and Swiss native 5-to-6 year-old kindergarteners. Results showed the immigrant
      children were less fluent in the local language compared to native Swiss
      classmates. Moreover, results from structural equation models, with bootstrap
      tests of indirect effects, indicated that social behaviors mediated the link
      between LLC and the quality of children's peer relationships. Implications of
      these findings for school professionals are discussed, such as the need to help
      immigrant children make a smoother transition to their host communities by
      providing additional language and social supports while children acculturate and
      acclimate to their new surroundings and peer group.

PMID- 22386121
TI  - Validating the Student-Teacher Relationship Scale: testing factor structure and
      measurement invariance across child gender and age in a Dutch sample.
AB  - The Student-Teacher Relationship Scale (STRS) is widely used to examine teachers'
      relationships with young students in terms of closeness, conflict, and
      dependency. This study aimed to verify the dimensional structure of the STRS with
      confirmatory factor analysis, test its measurement invariance across child gender
      and age, improve its measurement of the dependency construct, and extend its age
      range. Teachers completed a slightly adapted STRS for a Dutch sample of 2335
      children aged 3 to 12. Overall, the 3-factor model showed an acceptable fit.
      Results indicated metric invariance across gender and age up to 8years. Scalar
      invariance generally did not hold. Lack of metric invariance at ages 8 to 12
      primarily involved Conflict items, whereas scale differences across gender and
      age primarily involved Closeness items. The adapted Dependency scale showed
      strong invariance and higher internal consistencies than the original scale for
      this Dutch sample. Importantly, the revealed non-invariance for gender and age
      did not influence mean group comparisons.

PMID- 22386122
TI  - Does perceived teacher affective support matter for middle school students in
      mathematics classrooms?
AB  - The purpose of the present study was to explore the importance of perceived
      teacher affective support in relation to sense of belonging, academic enjoyment,
      academic hopelessness, academic self-efficacy, and academic effort in middle
      school mathematics classrooms. A self-report survey was administered to 317
      seventh- and eighth-grade students in 5 public middle schools. Structural
      equation modeling indicated significant associations between perceived teacher
      affective support and middle school students' motivational, emotional, and
      behavioral outcomes. The structural model explained a significant proportion of
      variance in students' sense of belonging (42%), academic enjoyment (43%), self
      efficacy beliefs (43%), academic hopelessness (18%), and academic effort (32%) in
      mathematics classrooms. In addition to providing the basis for a concise new
      measure of perceived teacher affective support, these findings point to the
      importance of students' perceptions of the affective climate within learning
      environments for promoting academic enjoyment, academic self-efficacy, and
      academic effort in mathematics.

PMID- 22386123
TI  - Ethnic incongruence and the student-teacher relationship: the perspective of
      ethnic majority teachers.
AB  - Among 36 ethnic-Dutch school teachers in the Netherlands, the present study
      examined the role of ethnic incongruence in perceived student-teacher
      relationship quality. Teachers rated their relationships with 59 Turkish-Dutch,
      62 Moroccan-Dutch, and 109 ethnic-Dutch students attending grades 4 through 6
      (M(age)=10.81 years, SD=1.05). On average, relationships were less favorable for
      the Moroccan-Dutch students only. However, the effects of ethnic incongruence
      were most pronounced among students with strong perceived
      inattention/hyperactivity and among teachers endorsing lower levels of
      multiculturalism (the view that different cultures deserve equal treatment).
      Results support the notion that ethnically incongruent relationships may be
      perceived as less favorable than ethnically congruent ones due to cultural
      misunderstandings and intergroup bias. Practical implications are discussed.

PMID- 22386124
TI  - Assessing the reliability of Curriculum-Based Measurement: an application of
      Latent Growth Modeling.
AB  - The purpose of this study was to demonstrate the use of Latent Growth Modeling
      (LGM) as a method for estimating reliability of Curriculum-Based Measurement
      (CBM) progress-monitoring data. The LGM approach permits the error associated
      with each measure to differ at each time point, thus providing an alternative
      method for examining of the reliability of CBM reading aloud data over repeated
      measurements. The analysis revealed that the reliability of CBM data was not a
      fixed property of the measure, but it changed with time. The study demonstrates
      the need to consider reliability in new ways with respect to the use of CBM data
      as repeated measures.

PMID- 22386126
TI  - Hyperglycosylated hCG and pregnancy failures.
AB  - Considerable evidence indicates that one third of early pregnancy failures,
      spontaneous abortions and biochemical pregnancies, are due to chromosomal
      abnormalities, and two thirds are due to inappropriate implantation. These
      findings led us to investigate the role of hyperglycosylated hCG, an important
      pregnancy implantation signal, in pregnancy failures. We used urinary hCG
      determinations to evaluate a total of 127 pregnancies on the day of implantation,
      as marked by a positive urinary hCG. These included 81 normal term pregnancies,
      18 spontaneous abortion pregnancies, and 28 biochemical pregnancies. Of the
      normal term pregnancies, the mean+/-standard deviation concentration of
      hyperglycosylated hCG was 5.4+/-4.3 mIU/ml equivalents, and the percentage of
      hyperglycosylated hCG was 88+/-17%. All term pregnancies produced
      hyperglycosylated hCG>51%. Of the 18 cases that spontaneously aborted, both the
      mean hyperglycosylated hCG (1.9+/-2.0 mIU/ml equivalents) and the percentage of
      hyperglycosylated hCG (41+/-33%) were significantly lower than in the normal
      pregnancy group. Only 4/18 spontaneously aborting pregnancies produced more than
      51% hyperglycosylated hCG on the day of implantation. Similarly, of the 28
      biochemical pregnancies, both the mean hyperglycosylated hCG (0.63+/-1.3 mIU/ml
      equivalents) and the percentage of hyperglycosylated hCG (21+/-29%) were
      significantly lower than in the normal pregnancy group. Only 4/28 pregnancies
      produced more than 51% hyperglycosylated hCG. Low hyperglycosylated hCG
      concentrations are associated with pregnancy failure. Whether this association is
      a primary cause of pregnancy failure or is simply a marker for an abnormal
      conceptus requires further investigation.

PMID- 22386125
TI  - Interleukin-18 promoter polymorphisms and risk of idiopathic recurrent pregnancy
      loss in a Tunisian population.
AB  - IL-18 is a pro-inflammatory cytokine that regulates the differentiation and
      effector functions of CD4+ (Th1) and CD8+ (CTL) T cells, which are implicated in
      the pathogenesis of recurrent pregnancy loss (RPL). We investigated the
      association of the IL-18 gene promoter single nucleotide polymorphisms (SNPs) 
      656C/A (rs1946519), -137G/C (rs187238), -119A/C (rs360718), and -105G/A
      (rs360717), by TaqMan assays in analysis in 470 Tunisian women comprising 235 RPL
      cases and 235 multi-parous controls. The association of IL-18 alleles, genotypes,
      and haplotypes with RPL was evaluated by Fisher's exact test and regression
      analysis. The frequency of minor alleles -105G/A (P<0.001) and -656C/A (P<0.001),
      but not -119A/C (P=0.93) or -137G/C (P=0.32), were higher in RPL cases.
      Significant differences were also noted in the genotype distribution of -105G/A
      (P<0.001) and -656C/A (P<0.001) between cases and controls. Four-locus (-656C/A, 
      137G/C, -119A/C, -105G/A) IL-18 haplotype analysis identified AGAA (corrected
      P<0.001), and CGAA (corrected P<0.001) haplotypes to be associated with increased
      RPL risk, after adjusting for age and BMI. These results demonstrate that -105G/A
      and -656C/A IL-18 variants are significantly associated with RPL.

PMID- 22386127
TI  - Serum interleukin-1beta, interleukin-8 and anti-heat shock 60 Chlamydia
      trachomatis antibodies as markers of ectopic pregnancy.
AB  - Anti-Chlamydial trachomatis (anti-CT) responses, particularly anti-heat shock 60
      (Hsp60), antibodies confer a higher risk of ectopic pregnancy. With emerging
      evidence supporting the pivotal role of interleukin-1beta (IL-1beta) and IL-8 in
      the immunopathogenesis of CT-specific tubal obstruction, we determined anti-CT
      Hsp60 antibody reactivity and serum concentrations of IL-1beta and IL-8 in failed
      pregnancies consisting of 30 consecutive ectopic pregnancies and 30 missed
      abortions, with 32 viable intrauterine pregnancies tested as normal controls.
      ELISAs were utilised to measure IgA or IgG anti-CT major outer membrane outer
      protein (MOMP) antibodies, IgG anti-CT Hsp60 antibodies and IL-1beta and IL-8.
      IgG anti-CT Hsp60 antibodies were more prevalent in ectopic pregnancy cases
      (43.3%, 13/30) than in intrauterine pregnancies (16%, 5/32, p=0.016). All 13
      ectopic pregnancy anti-CT Hsp60-positive cases had anti-CT MOMP antibodies. CT
      specific antibodies were more frequent in merged ectopic pregnancy and missed
      abortions cases (35%, 21/60) than in intrauterine pregnancies (16%, p=0.049). The
      median (range) levels of IL-1beta in ectopic pregnancy, missed abortions and
      normal intrauterine pregnancies were 1.74 (0.2-8.7), 1.14 (0.2-16) and 1.22 (0.2
      16.2) pg/ml, respectively (p>0.05, for all). Serum IL-8 levels were comparable
      amongst groups: ectopic pregnancy (median [range]: 25.1 [18.3-1000]); missed
      abortions (32.9 [15.39-1000]); and intrauterine pregnancies (25.11 [18.3-1000]
      pg/ml). Anti-CT antibody-positive ectopic pregnancy had significantly lower IL
      1beta levels (1.29 [0.2-2.93]) pg/ml than sero-negative ectopic pregnancy cases
      (2.09 [1.10-8.70]) pg/ml, (p=0.022), but IL-8 did not differ. Our data
      demonstrate that anti-CT Hsp60 immunity is a predominant feature of ectopic
      pregnancy. We conclude that neither IL-1beta nor IL-8 can be considered markers
      of failed pregnancy, although lower levels of the former cytokine are associated
      with CT-related ectopic pregnancy.

PMID- 22386128
TI  - Liquid chromatography-tandem mass spectrometric assay for the mutated BRAF
      inhibitor vemurafenib in human and mouse plasma.
AB  - A bioanalytical assay for the mutated BRAF inhibitor vemurafenib was developed
      and validated. For the quantitative assay, human plasma samples were pre-treated
      using protein precipitation with water-acetonitrile (1/3, v/v) containing
      sorafenib as internal standard. The extract was directly injected into the
      chromatographic system. This system consisted of a sub-2 MUm particle,
      trifunctional bonded octadecyl silica column with isocratic elution using 0.01%
      (v/v) of formic acid in a mixture of water and methanol. The eluate was
      transferred into the electrospray interface with positive ionization and the
      analyte was detected in the selected reaction monitoring mode of a triple
      quadrupole mass spectrometer. The assay was validated in a 0.1-100 MUg/ml
      calibration range. Within day precisions were 1.6-3.2%, between day precisions
      2.7% and 8.2% and accuracies were between 99% and 106% for the whole calibration
      range. The drug was stable under all relevant conditions. Finally, the assay was
      successfully used to assess drug levels in a pharmacokinetic mouse study.

PMID- 22386129
TI  - The visual P3a in schizophrenia and bipolar disorder: effects of target and
      distractor stimuli on the P300.
AB  - Amplitude reduction of the P300 event-related potential has long been suggested
      as a marker for schizophrenia. However, recent research has shown that this
      reduction in the P300 amplitude is not specific to schizophrenia as it can also
      be observed in related illnesses such as bipolar disorder. Due to this lack of
      specificity the P300 elicited using traditional oddball paradigms may be a less
      valuable endophenotypic marker. The current study employed a cognitively
      demanding three-stimulus oddball paradigm to elicit the P300 to visual target and
      distracting stimuli. Patients with schizophrenia showed amplitude reductions of
      P300 components to targets, distractors and frequent stimuli. The P300 in
      patients with bipolar disorder was not significantly different from either group.
      The pattern of results may further the understanding of the nature of the
      impairment in schizophrenia.

PMID- 22386130
TI  - Effect of Psidium cattleianum leaf extract on enamel demineralisation and dental
      biofilm composition in situ.
AB  - OBJECTIVE: Previous evaluations of Psidium cattleianum leaf extract were not done
      in conditions similar to the oral environment. The aim of this study was to
      evaluate the effect of P. cattleianum leaf extract on enamel demineralisation,
      extracellular polysaccharide formation, and the microbial composition of dental
      biofilms formed in situ. DESIGN: Ten volunteers took part in this crossover
      study. They wore palatal appliances containing 4 enamel blocks for 14 days. Each
      volunteer dripped 20% sucrose 8 times per day on the enamel blocks. Twice a day,
      deionised water (negative control), extract, or a commercial mouthwash (active
      control) was dripped after sucrose application. On the 12th and 13th days of the
      experiment, plaque acidogenicity was measured with a microelectrode, and the pH
      drop was calculated. On the 14th day, biofilms were harvested and total anaerobic
      microorganisms (TM), total streptococci (TS), mutans streptococci (MS), and
      extracellular polysaccharides (EPS) were evaluated. Enamel demineralisation was
      evaluated by the percentage change of surface microhardness (%DeltaSMH) and
      integrated loss of subsurface hardness (DeltaKHN). The researcher was blinded to
      the treatments during data collection. RESULTS: The extract group showed lower
      TM, TS, MS, EPS, %DeltaSMH, and DeltaKHN values than the negative control group.
      There were no differences between the active and negative control groups
      regarding MS and EPS levels. There were no differences in pH drop between the
      extract and active control groups, although they were significantly different
      from the negative control group. For all other parameters, the extract differed
      from the active control group. CONCLUSION: Psidium cattleianum leaf extract
      exhibits a potential anticariogenic effect.

PMID- 22386131
TI  - Determination of parameters for the steric mass action model--a comparison
      between two approaches.
AB  - The application of mechanistic modeling for the optimization of chromatographic
      steps increased recently due to time efficiency of algorithms and rising
      calculation power. In the modeling of ion exchange chromatography steps, the
      sorption processes occurring on adsorbent particle surfaces can be simulated with
      the steric mass action (SMA) model introduced by Brooks and Cramer (1992) [14].
      In this paper, two approaches for the determination of SMA parameters will be
      carried out and discussed concerning their specific experimental effort, quality
      of results, method differences, reasons for uncertainties and consequences for
      SMA parameter determination: Approach I: estimation of SMA parameters based on
      gradient and frontal experiments according to instructions in Brooks and Cramer
      (1992) [14] and Shukla et al. (1998) [16]. Approach II: application of an inverse
      method for parameter estimation, resulting in SMA parameters that induce a best
      fit of chromatographic data to a mechanistic model for column chromatography.
      These approaches for SMA parameter determination were carried out for three
      proteins (ribonuclease A, cytochrome c and lysozyme) at pH 5 and pH 7. The
      results were comparable and the order of parameter values and their relations to
      the chromatographic data similar. Nevertheless, differences in the complexity and
      effort of methods as well as the parameter values themselves were observed. The
      comparison of methods demonstrated that discrepancies depend mainly on model
      sensitivities and additional parameters influencing the calculations. However,
      the discrepancies do not affect predictivity; predictivity is high in both
      approaches. The approach based on an inverse method and the mechanistic model has
      the advantage that not only retention times but also complete elution profiles
      can be predicted. Thus, the inverse method based on a mechanistic model for
      column chromatography is the most comfortable way to establish highly predictive
      SMA parameters lending themselves for the optimization of chromatography steps
      and process control.

PMID- 22386132
TI  - Magnetic resonance imaging of radial sclerosing lesions (radial scars) of the
      breast.
AB  - PURPOSE: To identify magnetic resonance (MR) imaging (MRI) features of radial
      sclerosing lesions (RSLs) of the breast. METHODS AND MATERIALS: The radiologic
      and pathologic records for 4629 consecutive patients undergoing MR examinations
      of the breast were retrospectively reviewed. Patients who received a pathologic
      diagnosis of RSL without atypia or carcinoma at surgical excision were
      identified. The MR images were evaluated according to the BI-RADS-MRI lexicon by
      two experienced breast radiologists. The frequency of morphologic and kinetic
      patterns and of BI-RADS-MRI assessment categories was calculated. RESULTS: Twenty
      nine patients with 29 surgically excised RSL were identified. Nine (31%) RSL were
      MR-occult; the remaining 20 (69%) RSL presented as masses (10/20, 50%),
      architectural distortions (5/20, 25%), non-mass lesions (4/20, 20%), and focus
      (1/20, 5%). Kinetic analysis was performed in 18 RSL: enhancement features were
      benign in 9 (50%) cases, suspicious in 7 (39%) cases and indeterminate in 2 (11%)
      cases. Twelve (41%) MR examinations were assessed as suspicious (BI-RADS-MRI 4
      and 5), and 17 (59%) as negative (BI-RADS-MRI 1) or benign (BI-RADS-MRI 2 and 3).
      CONCLUSION: RSLs are often visualized on MR imaging. Just as in mammography and
      sonography, RSL can have variable morphologic and kinetic features, and not
      infrequently they can mimic invasive carcinoma of the breast.

PMID- 22386133
TI  - Pancreatic neuroendocrine tumor: added value of fusion of T2-weighted imaging and
      high b-value diffusion-weighted imaging for tumor detection.
AB  - OBJECTIVES: To investigate the added value of fusion of high b-value diffusion
      weighted images (DWI) and T2-weighted (T2) MR images for the detection of
      pancreatic neuroendocrine tumors (PNT). METHODS: 18 patients with 18
      histologically proven PNT were included. Two radiologists independently and
      retrospectively reviewed four randomized images sets (T2+T1, DWI, T2+DWI, and
      DWI+T2 fusion). Lesion detection confidence level was assessed using a three
      grade score (no lesion; uncertain lesion and certain lesion); lesion size and
      signal intensity were recorded. Apparent diffusion coefficients (ADC) of tumor
      and adjacent pancreas were measured. RESULTS: Readers 1 and 2 respectively
      detected 14/18 and 16/18 lesions on T2+T1, 13/18 and 12/18 on DWI, 16/18 and
      15/18 on T2+DWI and 17/18 and 16/18 on DWI+T2 fusion. Lesion median size was 16
      mm (range: 7 mm-40 mm), 22% were hyperfunctioning (all insulinomas) and 72% were
      low-grade (Rindi 1). All tumors except one (with cystic component) showed lower
      ADC than adjacent pancreatic parenchyma. Fusion imaging had significantly better
      detection score by both authors (p<0.005) and provided the higher inter-reader
      agreement (kappa 0.7). DWI alone had the worst score for both readers.
      CONCLUSIONS: Fusion images improve the detection of PNT, especially in patients
      with small isointense lesions on conventional MR sequences.

PMID- 22386134
TI  - Differentiation of benign and malignant breast lesions: a comparison between
      automatically generated breast volume scans and handheld ultrasound examinations.
AB  - OBJECTIVE: To assess the diagnostic value of automated breast volume scanning
      (ABVS) or conventional handheld ultrasonography (HHUS) for the differentiation of
      benign and malignant breast lesions. MATERIALS AND METHODS: The study
      prospectively evaluated 239 lesions in 213 women who were scheduled for open
      biopsy. The patients underwent ABVS and conventional HHUS. The sensitivity,
      specificity, accuracy, false positive rate, false negative rate, and positive and
      negative predictive values for HHUS and ABVS images were calculated using
      histopathological examination as the gold standard. Additionally, diagnostic
      accuracy was further evaluated according to the size of the masses. RESULTS:
      Among the 239 breast lesions studied, pathology revealed 85 (35.6%) malignant
      lesions and 154 (64.4%) benign lesions. ABVS was similar to HHUS in terms of
      sensitivity (95.3% vs. 90.6%), specificity (80.5% vs. 82.5%), accuracy (85.8% vs.
      85.3%), positive predictive value (73.0% vs. 74.0%), and negative predictive
      value (93.3% vs. 94.1%). The area under the receiver operating characteristic
      (ROC) curve, which is used to estimate the accuracy of the methods, demonstrated
      only minor differences between HHUS and ABVS (0.928 and 0.948, respectively).
      CONCLUSIONS: The diagnostic accuracy of HHUS and ABVS in differentiating benign
      from malignant breast lesions is almost identical. However, ABVS can offer new
      diagnostic information. ABVS may help to distinguish between real lesions and
      inhomogeneous areas, find small lesions, and demonstrate the presence of
      intraductal lesions. This technique is feasible for clinical applications and is
      a promising new technique in breast imaging.

PMID- 22386135
TI  - A nationwide family study of pulmonary embolism: identification of high risk
      families with increased risk of hospitalized and fatal pulmonary embolism.
AB  - BACKGROUND: Family history is an important risk factor for deep venous
      thrombosis. However, few studies have determined the importance of family history
      of pulmonary embolism (PE). OBJECTIVE: This nationwide study aimed to determine
      the familial risks of fatal and hospitalized PE. METHODS: The Swedish Multi
      Generation Register for subjects aged 0 to 76 years old born since 1932 were
      linked to the Hospital Discharge Register and Cause of Death Register for the
      period 1964-2008. Standardized incidence ratios (SIRs) for first hospitalization
      or death (without previous hospitalization for PE) with a main diagnosis of PE
      were calculated for individuals whose parent or siblings were hospitalized with
      or died from PE, compared to those whose parent or siblings were not affected by
      PE. RESULTS: A total of 20,860 individuals were hospitalized for PE and 862 died
      due to primary fatal PE (without previous hospitalization for PE). The familial
      SIR for individuals with one sibling with hospitalized PE was 2.49 (95% CI 1.62
      3.83). The familial SIR for siblings with two affected probands was 114.29 (95%
      CI 56.57-223.95). The familial SIRs for individuals with a parent or sibling
      hospitalized for PE were significantly increased for fatal PE (1.76; 95% CI 1.38
      2.21) and hospitalized PE (2.13; 95% CI 2.04-2.23). Spouses had low overall
      familial risk for PE (1.09; 95% CI, 1.03-1.14). CONCLUSION: The high familial
      risk in multiplex sibling families suggests the existence of strong genetic risk
      factors for PE. Familial factors and possibly genetic factors are important risk
      factors for primary fatal pulmonary embolism.

PMID- 22386136
TI  - Economic analysis of recombinant activated factor VII versus plasma-derived
      activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia
      registry data from the Czech Republic.
AB  - INTRODUCTION: Several studies suggest that recombinant activated factor VII
      (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex
      concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not
      consider differences between treated patients. This study compared the
      pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds
      in inhibitor patients, taking co-variables into account. METHODS: The HemoRec and
      HemIS registries capture exhaustive bleeding data in inhibitor patients in the
      Czech Republic. For each bleed, patient and bleed characteristics, treatment
      outcomes and bypassing agent use were retrospectively analysed, and direct costs
      of care per bleed calculated. Generalised Linear Model regression methods with
      cluster effect were employed to account for the possibility of several bleedings
      from the same patient. RESULTS: There were 108 and 53 mild to moderate bleeds in
      the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were
      similar in both groups, deeper analyses revealed significant differences in time
      to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within <=
      12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with
      rFVIIa (336,852 [median, 290,696] CZK; ?12,760 [11,011]) than pd-aPCC (522,768
      [341,310] CZK; ?19,802 [12,928]) (P = 0.002). Results were maintained after
      controlling for potential co-variables (bleed nature, time to treatment, target
      joints). CONCLUSIONS: The lower total treatment costs per bleed with rFVIIa than
      pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in
      mild to moderate bleeds. Time to bleed resolution was also significantly shorter
      with rFVIIa. These results were maintained when controlled for potential
      confounders.

PMID- 22386137
TI  - Reduced clot-stability during the first 6 hours after aneurysmal subarachnoid
      haemorrhage--a prospective case-control study.
AB  - INTRODUCTION: Early rebleeding is an important cause of death and disability
      following aneurysmal subarachnoid haemorrhage (SAH). Recent studies have shown
      that 50-90% of the rebleedings occurred within the first 6 hours after the
      primary bleeding. The mechanism leading to rebleeding remains to be established.
      In the present prospective case-control study we hypothesize that patients with
      SAH develop a coagulopathy characterized by reduced clot stability during the
      early period after the initial bleeding. METHODS: Patients with aneurysmal SAH
      was studied with a dynamic clot lysis assay and markers of fibrinolysis and clot
      stabilizers in blood samples taken within and after 6 hours after onset of
      bleeding. Results were compared with blood samples from age and gender matched
      healthy controls. RESULTS: 36 patients were enrolled, 26 patients had blood
      samples collected within 6 hours after the initial bleeding whereas 10 patients
      had blood samples taken later than 6 hours after the initial bleeding. Patients
      demonstrated significantly reduced clot stability during the first 6 hours after
      initial bleeding. Fibrinolytic activity was increased during the first 6 hours
      along with the inhibitors of fibrinolysis whereas the modulators of fibrinolysis
      were reduced or inactivated. CONCLUSION: During the first 6 hours after SAH
      patients exhibit reduced clot-stability. Probably a consequence of activated
      fibrinolysis in combination with reduced or inactivated factor XIII and thrombin
      activable fibrinolysis inhibitor.

PMID- 22386138
TI  - Peptide-induced fluorescence quenching of conjugated polyelectrolyte for label
      free, ultrasensitive and selective assay of protease activity.
AB  - We report here a label-free method for ultrasensitive and selective assay of
      protease activity based on the peptide-induced fluorescence quenching of
      conjugated polyelectrolyte (PPESO(3)). It is very interesting to find that there
      is a critical length of oligo-polyarginine (i.e., Arg(5)) below which 1) the
      quenching efficiency of PPESO(3) is sharply decreased, and more importantly, 2)
      the trypsin-catalyzed hydrolysis is greatly slowed down. This opens good
      opportunities for not only the ultrasensitive assay of trypsin, but the specific
      detection of other proteases if carefully designing an appropriate peptide length
      and the cleavage site. Herein, the enzyme selected as a proof of concept is
      chymotrypsin. Due to the essence that any cleavage of the designed peptide probes
      will result in a notable decrease or even a complete loss of their capability to
      quench the emission of PPESO(3), the limits of detection for trypsin and
      chymotrypsin have been found as low as 0.25 ng/mL (11 pM) and 0.15 ng/mL (6 pM),
      respectively. Both are superior to those of most previous methods by 1-2 orders
      or higher.

PMID- 22386140
TI  - Inferior vena cava resection and reconstruction for retroperitoneal tumor
      excision.
AB  - OBJECTIVE: This study reviews the results of en bloc resection of the inferior
      vena cava (IVC) for malignant tumor excision and reconstruction. METHODS: A
      prospective database was reviewed. IVC resection was categorized as suprarenal,
      perirenal, infrarenal, or extensive (>one segment resected). Repairs were divided
      into primary, patch, or circumferential. Tumor type, perioperative morbidity,
      mortality, and graft patency were recorded. RESULTS: Between 1990 and 2011, 47
      patients (21 women; mean age, 56; range, 35-89 years) underwent IVC resection for
      en bloc tumor excision. Sarcomas were most common (36 [77%]: 30 primary IVC).
      Eleven patients had primary IVC repair, nine patch repair (two autogenous), and
      27 had circumferential replacement with a polytetrafluoroethylene ringed graft.
      Extensive IVC reconstruction in 18 patients included the entire IVC, with renal
      (RV) and hepatic vein reimplantation in eight; suprarenal and perirenal in six
      (seven RVs reimplanted); and infrarenal and perirenal in four (four RVs
      reimplanted). Nine single-segment IVC replacements were infrarenal. Morbidity was
      10.6%: one each with bowel obstruction, chyle leak, renal failure with complete
      recovery (left RV reimplant, right nephrectomy), reoperation for bleeding, and
      IVC graft thrombosis. Morbidity did not differ by type of reconstruction. There
      was no mortality. Follow-up ranged from 1.5 to 216 months (18 years) with a mean
      of 3.5 years. Computed tomography or duplex scans were available in 28 of 47
      patients and in 15 of 27 patients in group 3 at a mean follow-up of 36 and 20
      months, respectively. One IVC graft thrombosis was documented at 10 months after
      chemotherapy/sepsis. Tumor recurrence caused three graft stenoses. Cumulative 5
      year patency in group 3 was 80% (imaging) and 92% (clinical). Lower extremity
      edema was universally avoided. Cumulative 5-year survival for the series was 45%
      +/- 8.5%. Mean long-term survival was 5.8 +/- 0.56 years (range, 4 months-17
      years), with a significant difference between primary or patch (mean, 6.5 years)
      and circumferential or extensive repair (mean, 4.2 years; P < .005). Cumulative
      (47% vs 52%) and mean (3.1 vs 3.6 years; P > .12) survival was similar between
      patients with single-segment and extensive IVC resection and replacement.
      CONCLUSIONS: IVC resection and reconstruction for en bloc tumor excision is safe,
      even when extensive repairs are necessary. Replacement of the IVC with prosthetic
      graft avoids extremity venous complications and likely contributes to quality of
      survival. Survival depends on tumor behavior and degree of IVC involvement, where
      primary and patch repair has a better prognosis than circumferential resection.

PMID- 22386142
TI  - The birth of vascular surgery in Australia.

PMID- 22386141
TI  - Remodeling leads to distinctly more intimal hyperplasia in coronary than in
      infrainguinal vein grafts.
AB  - BACKGROUND: Flow patterns and shear forces in native coronary arteries are more
      protective against neointimal hyperplasia than those in femoral arteries. Yet,
      the caliber mismatch with their target arteries makes coronary artery bypass
      grafts more likely to encounter intimal hyperplasia than their infrainguinal
      counterparts due to the resultant slow flow velocity and decreased wall stress.
      To allow a site-specific, flow-related comparison of remodeling behavior,
      saphenous vein bypass grafts were simultaneously implanted in femoral and
      coronary positions. METHODS: Saphenous vein grafts were concomitantly implanted
      as coronary and femoral bypass grafts using a senescent nonhuman primate model.
      Duplex ultrasound-based blood flow velocity profiles and vein graft and target
      artery dimensions were correlated with dimensional and histomorphologic graft
      remodeling in large, senescent Chacma baboons (n = 8; 28.1 +/- 4.9 kg) during a
      24-week period. RESULTS: At implantation, the cross-sectional quotient (Q(c))
      between target arteries and vein grafts was 0.62 +/- 0.10 for femoral grafts vs
      0.17 +/- 0.06 for coronary grafts, resulting in a dimensional graft-to-artery
      mismatch 3.6 times higher (P < .0001) in coronary grafts. Together with different
      velocity profiles, these site-specific dimensional discrepancies resulted in a
      57.9% +/- 19.4% lower maximum flow velocity (P = .0048), 48.1% +/- 23.6% lower
      maximal cycling wall shear stress (P = .012), and 62.2% +/- 21.2% lower mean
      velocity (P = .007) in coronary grafts. After 24 weeks, the luminal diameter of
      all coronary grafts had contracted by 63%, from an inner diameter of 4.49 +/-
      0.60 to 1.68 +/- 0.63 mm (P < .0001; subintimal diameter: -41.5%; P = .002),
      whereas 57% of the femoral interposition grafts had dilated by 31%, from 4.21 +/-
      0.25 to 5.53 +/- 1.30 mm (P = .020). Neointimal tissue was 2.3 times thicker in
      coronary than in femoral grafts (561 +/- 73 vs 240 +/- 149 MUm; P = .001).
      Overall, the luminal area of coronary grafts was an average of 4.1 times smaller
      than that of femoral grafts. CONCLUSIONS: Although coronary and infrainguinal
      bypass surgery uses saphenous veins as conduits, they undergo significantly
      different remodeling processes in these two anatomic positions.

PMID- 22386143
TI  - Escherichia coli primary aortitis presenting as sequelae of incompletely treated
      urinary tract infection.
AB  - We report a rare case of nonaneurysmal infectious aortitis (IA) with the
      causative microorganism being Escherichia coli. The patient was a 78-year-old man
      who presented with a 3-week history of abdominal pain, fevers, and anorexia after
      treatment for a urinary tract infection. The patient had positive blood cultures
      and a computed tomography scan that had signs of IA. He was treated with
      intravenous antibiotics and extra-anatomic revascularization with excision and
      debridement of the infected aortic segment with a good outcome. IA is an uncommon
      condition with a high mortality rate; however, if diagnosed early, it can be
      successfully treated.

PMID- 22386144
TI  - Comparing the embolic potential of open and closed cell stents during carotid
      angioplasty and stenting.
AB  - OBJECTIVE: We sought to determine the effects of open (O) and closed (C) cell
      stents on the size and number of embolic particles generated during carotid
      artery stenting (CAS) and assess the impact on outcome. METHODS: Embolic debris
      from carotid filters after CAS was analyzed using photomicroscopy and imaging
      software. Patient comorbidities, preoperative cerebrovascular symptoms, stent
      type, and outcomes (perioperative major adverse events) were examined. RESULTS:
      Carotid filters from 173 consecutive CAS procedures (O, 125 and C, 48) were
      reviewed. The mean age was 70.9 +/- 9.2 years; 58% were men. Mean stenosis was
      88.2% +/- 8.1%; 36.6% had neurological symptoms preprocedurally. There was no
      difference in preoperative symptoms between the two groups (O, 38.7% vs C, 31.3%;
      P = not significant [NS]). However, closed cell stent use was associated with
      higher degree of stenosis (O, 87.2% +/- 8.0% vs C, 90.6% +/- 7.8%; P = .01), an
      older age (O, 70.0 +/- 8.6 years vs C, 73.4 +/- 10.2 years; P = .03), and
      peripheral arterial disease (21.1% vs 43.5%; P = .01). A larger mean particle
      size was observed in patients treated with open cell stents compared to closed
      cell stents (O, 416.5 +/- 335.7 MUm vs C, 301.1 +/- 251.3 MUm; P = .03). There
      was no significant difference in the total number of particles (O, 13.8 +/- 21.5
      vs C, 17.6 +/- 19.9; P = NS), periprocedural stroke (P = NS), and major adverse
      events between the two groups (P = NS). CONCLUSIONS: Open cell stents are
      associated with a larger mean particle size compared to closed cell stents. No
      impact on procedural outcomes based on stent type was observed.

PMID- 22386145
TI  - Short-term outcome analysis of radiofrequency ablation using ClosurePlus vs
      ClosureFast catheters in the treatment of incompetent great saphenous vein.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a widely accepted alternative to
      high ligation with proximal stripping of the great saphenous vein (GSV) in the
      treatment of lower extremity venous insufficiency. This study compared short-term
      outcomes of two generations of (VNUS Closure) RFA catheters, ClosurePlus (CP) and
      ClosureFast (CF). METHODS: From February 2005 to April 2009, a total of 667
      consecutive office-based RFA procedures were performed in our institution. CP
      catheters were used in the initial 312 lower extremity cases and CF catheters in
      the 355 cases that followed. The technique used for both catheters were as per
      the manufacturer's recommendations. Postoperative duplex scans were completed to
      document the following endpoints: GSV obliteration; incidence of deep venous
      thrombosis (DVT); superficial venous thrombosis (SVT); and presence of loose or
      floating thrombus proximal to the treated GSV segment. RESULTS: Of the 667 cases,
      98% had available duplex scan studies within 1 week from completion of the
      procedure. Complete obliteration of the GSV on duplex scan studies was noted in
      98% of 343 cases using the CF catheter and 88% of 312 cases using the CP catheter
      (P < .001). No case of DVT was detected in those treated with the CF catheter,
      whereas DVT occurred in 3.5% of cases treated with the CP catheter (P < .001).
      Incidence of SVT was 10% and 15%, respectively, for CF and CP (P < .08). Loose
      thrombus proximal to the GSV was identified in 7% of cases using CF and 6% of
      cases using CP (P = .80). No embolic episodes were observed clinically.
      CONCLUSIONS: CF catheters are superior to CP catheters in terms of GSV
      obliteration and nonincidence of postoperative DVT. The absence of DVT may likely
      be due to the commencement of ablation at 2 cm from the GSV-common femoral vein
      junction.

PMID- 22386146
TI  - A new imaging method for assessment of aortic dissection using four-dimensional
      phase contrast magnetic resonance imaging.
AB  - INTRODUCTION: Medical management of type B aortic dissection can result in
      progressive dilation of the false lumen and poor long-term outcome. Recent
      studies using models of aortic dissection have suggested flow characteristics,
      such as stroke volume, velocity, and helicity, are related to aortic expansion.
      The aim of this study was to assess whether four-dimensional phase-contrast
      magnetic resonance imaging (4D PC-MRI) can accurately visualize and quantify flow
      characteristics in patients with aortic dissection and whether these features are
      related to the rate of aortic expansion. METHODS: Twelve consecutive patients
      with medically treated type B thoracic aortic dissection underwent a three
      dimensional (3D) MRI anatomy scan using a blood pool contrast agent. Two
      dimensional phase contrast MRI data (2D PC-MRI) were acquired in the ascending
      and descending aorta and 4D PC-MRI data were acquired in the entire thoracic
      aorta. The 2D PC-MRI measurements were used to assess the quality of the 4D PC
      MRI velocity data. Stroke volume, velocity, and the direction of flow were
      calculated using 4D PC-MRI and related to the rate of aortic expansion measured
      on contrast-enhanced computed tomography. RESULTS: Comparison of 2D PC-MRI and 4D
      PC-MRI measurements showed good correlation (Pearson R(2) = 0.98; 95% confidence
      interval [CI], 0.9818-0.9953; P < .0001) and no proportional bias (bias = 1.0 mL;
      standard deviation, 4.6). The median aortic growth rate was 6.1 mm/y
      (interquartile range [IQR], 1.1-15.1 mm/y), and this correlated well with the
      growth rate of the false lumen (Spearman rho = 0.62; 95% CI, 0.06-0.89; P =
      .0347). False lumen thrombosis (FLT) was seen in 7 of 12 patients and was not
      associated with reduced aortic expansion rate (FLT present: 11.4 mm/y; IQR, 3.6
      21.4) vs FLT absent: 9.9 mm/y; IQR, 3.4-24.2; Mann-Whitney P = .8763). False
      lumen stroke volume and velocity were associated with more rapid aortic expansion
      (rho = 0.80 [95% CI, 0.39-0.94; P = .0029] and rho = 0.59 [95% CI, 0.09-0.87; P =
      .0480] respectively). The position of the dominant entry tear was associated with
      rapid expansion, which tended to be higher with distal vs proximal entry tears
      (distal, 21.4 mm/y [IQR, 11.4-48.9] vs proximal, 5.5 mm/y [IQR, 3.4-16.6]; Mann
      Whitney P = .096). Helical flow was seen in the false lumen in 8 of 12 patients
      and was related to the rate of aortic expansion (rho = 0.83, P = .0154).
      CONCLUSIONS: 4D PC-MRI can be accurately applied to visualize and quantify flow
      characteristics in patients with aortic dissection. Stroke volume, velocity,
      distal dominant entry tears, and helical flow are related to the rate of aortic
      expansion. This study demonstrates the potential of this new imaging method. A
      larger prospective study is now required to measure flow characteristics and
      determine their predictive value for risk stratification of patients with aortic
      dissection.

PMID- 22386147
TI  - Determination of enrofloxacin by room-temperature phosphorimetry after solid
      phase extraction on an acrylic polymer sorbent.
AB  - A phosphorimetric method was developed to enable the determination of
      enrofloxacin using photochemical derivatization which was used to both improve
      detection limits and to minimize the uncertainty of measurements. Phosphorescence
      was induced on cellulose containing TlNO(3). Absolute limit of detection at the
      ng range and linear analytical response over three orders of magnitude were
      achieved. A metrological study was made to obtain the combined uncertainty value
      and to identify that the precision was mainly affected by the changing of
      substrates when measuring the signal from each replicate. Pharmaceutical
      formulations containing enrofloxacin were successfully analyzed by the method and
      the results were similar to the ones achieved using a HPLC method. A solid phase
      extraction on an acrylic polymer was optimized to separate enrofloxacin from
      interferents such as diclofenac and other components from biological matrices,
      which allowed the successful use of the method in urine analysis.

PMID- 22386149
TI  - ProClusEnsem: predicting membrane protein types by fusing different modes of
      pseudo amino acid composition.
AB  - Knowing the type of an uncharacterized membrane protein often provides a useful
      clue in both basic research and drug discovery. With the explosion of protein
      sequences generated in the post genomic era, determination of membrane protein
      types by experimental methods is expensive and time consuming. It therefore
      becomes important to develop an automated method to find the possible types of
      membrane proteins. In view of this, various computational membrane protein
      prediction methods have been proposed. They extract protein feature vectors, such
      as PseAAC (pseudo amino acid composition) and PsePSSM (pseudo position-specific
      scoring matrix) for representation of protein sequence, and then learn a distance
      metric for the KNN (K nearest neighbor) or NN (nearest neighbor) classifier to
      predicate the final type. Most of the metrics are learned using linear
      dimensionality reduction algorithms like Principle Components Analysis (PCA) and
      Linear Discriminant Analysis (LDA). Such metrics are common to all the proteins
      in the dataset. In fact, they assume that the proteins lie on a uniform
      distribution, which can be captured by the linear dimensionality reduction
      algorithm. We doubt this assumption, and learn local metrics which are optimized
      for local subset of the whole proteins. The learning procedure is iterated with
      the protein clustering. Then a novel ensemble distance metric is given by
      combining the local metrics through Tikhonov regularization. The experimental
      results on a benchmark dataset demonstrate the feasibility and effectiveness of
      the proposed algorithm named ProClusEnsem.

PMID- 22386148
TI  - Comparison of different EEG features in estimation of hypnosis susceptibility
      level.
AB  - Hypnosis has long been known to be associated with heightened control over
      physical processes and researchers put it under consideration because of its
      usage as a therapeutic tool in many medical and psychological problems.
      Determination of hypnosis susceptibility level is important before prescribing
      any hypnotic treatment. In this study different features are introduced to
      classify hypnotizability levels. These features were extracted from
      electroencephalogram (EEG) signals which were recorded from 32 subjects during
      hypnosis suggestion. Based on the obtained result, a method was suggested to
      estimate the hypnosis susceptibility level from hypnosis EEG signals instead of
      using traditional clinical subjective tests.

PMID- 22386150
TI  - Valvular lesions in patients with systemic lupus erythematosus and
      antiphospholipid syndrome: an old disease but a persistent challenge.
AB  - Valvular heart disease is common in systemic lupus erythematosus (SLE) and
      antiphospholipid syndrome. Immunologic insult plays a fundamental role in its
      pathogenesis but data on the role of antiphospholipid antibodies have been
      inconsistent, particularly regarding SLE-associated valvular lesions. Although
      timely diagnosis is essential to prevent progression of valvular lesions,
      treatment remains a challenge because of the lack of large systematic studies.
      This article reviews and summarizes recent information relating to valvular
      damage in these two autoimmune diseases, and highlights some important questions
      that need to be answered.

PMID- 22386151
TI  - From flakes to grooves: a technical shift in antlerworking during the last
      glacial maximum in southwest France.
AB  - The evolution of antlerworking technology in Paleolithic and Mesolithic Europe,
      especially the production of splinters, is usually described as a cumulative
      process. A progressive increase in blank standardization and productivity was
      prompted by the application of a key technical process, the groove and splinter
      technique (GST). The Badegoulian, however, appears as an interruption in this
      continuum. According to the original definition of this post-Solutrean, pre
      Magdalenian archeological culture, one of its distinctive features is the absence
      of the GST and the manufacture of antler blanks by knapping only. However, this
      conception has been recently questioned, leading to an alternative hypothesis
      suggesting that both GST and knapping were used during the Badegoulian. In this
      article, we present new evidence from several sites in southwest France, which
      sheds new light on the issue of Badegoulian antlerworking and the transition with
      the subsequent Lower Magdalenian. Our study is based on two complementary
      methods: the technological analysis of antler assemblages well-dated to the
      Badegoulian (Le Cuzoul de Vers) or to the Lower Magdalenian (La Grotte des
      Scilles, Saint-Germain-la-Riviere), and the direct (14)C dating of specific
      antler artifacts from mixed or problematic contexts (Cap-Blanc, Reverdit and
      Lassac). The results firmly establish that, in southwest France, knapping is the
      only method used for the production of antler splinters during the Badegoulian,
      before ca. 20,500 cal BP (calibrated years before present), and that it is
      rapidly replaced by the GST at the beginning of the Lower Magdalenian, after ca.
      20,500 cal BP. This technical shift is not linked to an influx of new human
      populations, environmental change or the supposed economic advantages of the GST.
      Instead, it must be understood as one of the expressions of a broader
      reconfiguration of the technical world that starts to take shape in the middle of
      the Last Glacial Maximum.

PMID- 22386152
TI  - Phenotypic correlates of male reproductive success in western gorillas.
AB  - Sexual selection is thought to drive the evolution of sexually dimorphic traits
      that increase male reproductive success. Despite a large degree of sexual
      dimorphism among haplorhine primates, phenotypic traits that may influence the
      reproductive success of males are largely unstudied due to long life spans and
      the difficulties in quantifying such traits non-invasively. Here we employ
      digital photogrammetry of body length and crest size, as well as ranking of the
      gluteal muscle size, to test whether these sexually dimorphic traits are
      associated with long-term measures of male reproductive success in western
      gorillas. Among 19 adult male gorillas monitored for up to 12.5 years, we found
      that all three phenotypic traits were positively correlated with the average
      number of mates per male, but only crest size and gluteal muscle size were
      significantly correlated with offspring survival and the annual rate of siring
      offspring that survive to weaning age. We discuss why such sexually dimorphic
      traits might be under ongoing selection in gorillas and other species.

PMID- 22386153
TI  - Estimating the volume of alcohol-based hand rub required for a hand hygiene
      program.
AB  - BACKGROUND: Providing alcohol-based hand rub (ABHR) at the point of care is a key
      success factor in enabling health care providers to achieve optimal hand hygiene
      practices. There are few tools available for health care organizations to assess
      the number of points of care, estimate the number of hand hygiene indications at
      each point of care, and estimate the anticipated volume of ABHR required to
      support a hand hygiene program. METHODS: We developed an assessment tool to
      systematically evaluate the environmental hand hygiene needs in diverse care
      settings across a multisite health care organization. RESULTS: We identified
      1,103 points of care in 34 clinical units, of which only 53% had ABHR at point of
      care. There are an estimated 171,468,240 (95% confidence interval: 146,844,406
      191,871,179) hand hygiene indications per year in our in-patient and emergency
      areas. If 100% compliance with hand hygiene is achieved, 240,056 L of ABHR will
      be required each year. CONCLUSIONS: Our environmental assessment was invaluable
      in estimating the number of hand hygiene indications by unit and the logistical
      and financial requirements to implement a hand hygiene program. Other health care
      organizations may find this a useful framework to estimate their own
      environmental hand hygiene needs.

PMID- 22386154
TI  - Decreasing ventilator-associated pneumonia in the intensive care unit: a
      sustainable comprehensive quality improvement program.
AB  - An intensive care unit implemented an oral care bundle to decrease ventilator
      associated pneumonia (VAP). A retrospective analysis comparing like time periods
      revealed the VAP rate per 1,000 ventilator-days dropped significantly from 10.5
      to 0 (P = .016). The oral care bundle remains in place as of end of May 2011 and
      has proven to be a sustainable method for VAP prevention.

PMID- 22386156
TI  - Radiology's role in enhanced international health care.

PMID- 22386155
TI  - Prevalence of susceptibility to tetanus and diphtheria in health care workers in
      Catalonia.
AB  - A seroprevalence study of tetanus and diphtheria was carried out in a sample of
      537 health care workers in Catalonia. The prevalence of protective antibodies
      against tetanus was 93.9% (95% confidence interval: 91.5-95.7). The prevalence of
      protective antibodies against diphtheria was 46.4% (95% confidence interval: 42.1
      50.7). Tetanus protection should be improved in health care workers born before
      1975. The immune status against diphtheria was poor, with less than half of
      people born before 1975 correctly immunized.

PMID- 22386157
TI  - Society meetings.

PMID- 22386158
TI  - Patient-centered imaging: opportunities and challenges.

PMID- 22386159
TI  - The effects of bad math.

PMID- 22386160
TI  - Writing and being.

PMID- 22386161
TI  - ACR appropriateness criteria((r))acute respiratory illness in immunocompromised
      patients.
AB  - The respiratory system is often affected by complications of immunodeficiency,
      typically manifesting clinically as acute respiratory illness. Ongoing literature
      reviews regarding the appropriateness of imaging in these patients are critical,
      as advanced medical therapies such as stem cell transplantation, chemotherapy,
      and immunosuppressive therapies for autoimmune disease continue to keep high the
      population of immunosuppressed patients in our health care system today. This ACR
      Appropriateness Criteria((r)) topic describes clinical scenarios of acute
      respiratory illness in immunocompromised patients with cough, dyspnea, chest
      pain, and fever; in those with negative, equivocal, or nonspecific findings on
      chest radiography; in those with diffuse or confluent opacities on chest
      radiography; and in those in whom noninfectious disease is suspected. The use of
      chest radiography, chest CT, transthoracic needle biopsy, and nuclear medicine
      imaging are all discussed in the contexts of these clinical scenarios. The ACR
      Appropriateness Criteria are evidence-based guidelines for specific clinical
      conditions that are reviewed every 2 years by a multidisciplinary expert panel.
      The guideline development and review include an extensive analysis of current
      medical literature from peer-reviewed journals and the application of a well
      established consensus methodology (modified Delphi) to rate the appropriateness
      of imaging and treatment procedures by the panel. In those instances in which
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment.

PMID- 22386162
TI  - Web modules on professionalism and ethics.
AB  - Health care disciplines have always held resolutely to a commitment to
      professionalism and high ethical standards. With the present emphasis on public
      accountability, professionalism and ethics are receiving enhanced attention in
      health care education and practice. A challenge for radiologists, radiation
      oncologists, and medical physicists is to define the scope and depth of knowledge
      about professionalism and ethics that are necessary for the practice of the
      disciplines. A further challenge is to develop accessible educational materials
      that encompass this required knowledge. About 2 years ago, the ABR Foundation
      decided to address these challenges through the development of an ethics and
      professionalism curriculum and production of a series of Web-based educational
      modules that follow the curriculum. Six organizations agreed initially to
      contribute financially to construction of the curriculum and modules and were
      later joined by a seventh. The curriculum was developed by the ABR Foundation and
      included in a request for proposals that was widely distributed. Teams of authors
      for each of 10 modules were selected from respondents to the request for
      proposals. As the modules were developed, they were reviewed in 3 successive
      stages, including peer review by members of the ACR Committee on Professionalism
      and the RSNA-ACR Task Force on an Ethics Curriculum. After revisions were
      prepared in response to the reviews, the modules were translated into a format
      compatible with the e-learning platform on which they are mounted. The modules
      are now available to all who wish to study them.

PMID- 22386163
TI  - Business of radiology 101: the state of radiology business practice and health
      care policy curricula at US radiology residency programs.
AB  - PURPOSE: The aim of this study was to assess the prevalence, content, and
      perceptions of curricula focused on radiology business practice and health care
      policy at US radiology residency training programs. METHODS: The desired survey
      population was trainees and faculty members of radiology residency programs in
      the United States. Three anonymous survey instruments were distributed, including
      an e-mail survey to the membership of the ACR RFS, a paper survey to ACR RFS
      delegates attending the 2010 AMCLC, and an e-mail survey to the membership of the
      Association of Program Directors in Radiology (APDR). RESULTS: Response rates for
      the surveys were 12%, 25%, and 21%, respectively. Members of the APDR and RFS
      agreed that understanding and competency in business practice and health care
      policy topics are important to the future careers of residents (total favorable
      sentiment >86% for APDR members and >96% for RFS members). Most survey
      respondents' home institutions offer some form of a noninterpretive curriculum
      (91% of APDR respondents, 74% of RFS respondents), but the breadth of topics
      addressed and educational time devoted to these curricula were quite variable.
      Subjective effectiveness of curricula was infrequently rated as very effective by
      12% of APDR respondents and 6% of RFS respondents. CONCLUSIONS: Despite the
      perceived importance of radiology business practice and health care policy
      education, and residency training requirements in competencies related to these
      subjects that have been in place for more than a decade, curricula addressing
      these items still seem to be in a stage of acceptance and development. Further
      commitment to and innovation within these curricula are requisite in educating
      our future radiologists.

PMID- 22386164
TI  - Effective committees.
AB  - A committee is a group of people officially delegated to perform a function, such
      as investigating, considering, reporting, or acting on a matter. Some committees
      function like task forces and work on specific, time-limited projects. When the
      work is finished, the committees are no longer needed. These committees are
      called ad hoc committees. Other committees are standing committees. They are
      created by the standing orders, rules, by-laws, or regulations of an organization
      and exist and function indefinitely (eg, finance, membership, education,
      nomination). Both types of committees can form subcommittees if the workloads are
      heavy or complex in nature. Committees can be among the most important working
      forces of an organization. They serve as work units of the organization, taking
      work and breaking it into meaningful and manageable chunks. They efficiently
      carry out the work of the organization. Committee work should be a rewarding
      experience for both the members and the organization. Committees represent,
      involve, and serve members, as well as provide an important training ground for
      future leaders of an organization. New or inexperienced members can gain valuable
      insight into an organization and develop confidence by serving on committees.
      There are several key elements of effective committees, including (1) a clear,
      written purpose; (2) an effective committee chair; (3) thoughtfully appointed
      members; and (4) well-run meetings.

PMID- 22386165
TI  - Outbreak of bacterial meningitis among patients undergoing myelography at an
      outpatient radiology clinic.
AB  - PURPOSE: To investigate an outbreak of bacterial meningitis at an outpatient
      radiology clinic (clinic A) and to determine the source and implement measures to
      prevent additional infections. METHODS: A case was defined as bacterial
      meningitis in a patient undergoing myelography at clinic A from October 11 to 25,
      2010. Patients who underwent myelography and other procedures at clinic A during
      that period were interviewed, medical records were reviewed, and infection
      prevention practices were assessed. Case-patient cerebrospinal fluid (CSF)
      specimens, oral specimens from health care personnel (HCP), and opened iohexol
      vials were tested for bacteria. Bacterial isolates were compared using pulsed
      field gel electrophoresis. A culture-negative CSF specimen was tested using a
      real-time polymerase chain reaction assay. RESULTS: Three cases were identified
      among 35 clinic A patients who underwent procedures from October 11 to 25, 2010.
      All case-patients required hospitalization, 2 in an intensive care unit. Case
      patients had myelography performed by the same radiology physician assistant and
      technician on October 25; all patients who underwent myelography on October 25
      were affected. HCP did not wear facemasks and reused single-dose iohexol vials
      for multiple patients. Streptococcus salivarius (a bacteria commonly found in
      oral flora) was detected in the CSF of 2 case-patients (1 by culture, 1 using
      real-time polymerase chain reaction) and in HCP oral specimens; 1 opened iohexol
      vial contained Staphylococcus epidermidis. Pulsed-field gel electrophoresis
      profiles from the case-patient S salivarius and the radiology physician assistant
      were indistinguishable. CONCLUSIONS: Bacterial meningitis likely occurred because
      HCP performing myelography did not wear facemasks; lapses in injection practices
      may have contributed to transmission. Targeted education regarding mask use and
      safe injection practices is needed among radiology HCP.

PMID- 22386167
TI  - Radiation oncology quality: aggressiveness of cancer care near the end of life.
AB  - PURPOSE: Quality in cancer care is an issue that has come to the forefront over
      the past decade. Although the American Society of Clinical Oncology has developed
      extensive quality metrics and goals, such as limiting chemotherapy being provided
      within the last 14 days of a patient's life, there are no similar quality
      metrics, and few data, in the field of radiation oncology. METHODS: In this
      study, morbidity and mortality records from 2008 to 2011 were reviewed for
      patients at Indiana University who received radiation therapy (RT) within 30 days
      of death; 63 patients met those criteria. RESULTS: Analysis showed that 22.2% of
      patients had Karnofsky Performance Status Scale scores >80, whereas 66.7% of
      patients had scores < 60. Just over half of patients (52%) were still on
      treatment at death, and more than half of patients (54%) had completed less than
      half of their original RT plans. Six patients had their final treatments on the
      days of their deaths, and another 43 patients had their last treatments within 10
      days of death. Forty-eight percent of patients received RT for less than one
      fifth of their final month of life and 21% for more than half of their last month
      alive. CONCLUSIONS: These data are valuable in ongoing discussions of RT use at
      the end of life, especially as related to hospice underutilization.

PMID- 22386166
TI  - Do long radiology workdays affect nodule detection in dynamic CT interpretation?
AB  - PURPOSE: A previous study demonstrated decreased diagnostic accuracy for finding
      fractures and decreased ability to focus on skeletal radiographs after a long
      working day. Skeletal radiographic examinations commonly have images that are
      displayed statically. The aim of this study was to investigate whether diagnostic
      accuracy for detecting pulmonary nodules on CT of the chest displayed dynamically
      would be similarly affected by fatigue. METHODS: Twenty-two radiologists and 22
      residents were given 2 tests searching CT chest sequences for a solitary
      pulmonary nodule before and after a day of clinical reading. To measure search
      time, 10 lung CT sequences, each containing 20 consecutive sections and a single
      nodule, were inspected using free search and navigation. To measure diagnostic
      accuracy, 100 CT sequences, each with 20 sections and half with nodules, were
      displayed at preset scrolling speed and duration. Accuracy was measured using
      receiver operating characteristic curve analysis. Visual strain was measured via
      dark vergence, an indicator of the ability to keep the eyes focused on the
      display. RESULTS: Diagnostic accuracy was reduced after a day of clinical reading
      (P = .0246), but search time was not affected (P > .05). After a day of reading,
      dark vergence was significantly larger and more variable (P = .0098), reflecting
      higher levels of visual strain, and subjective ratings of fatigue were also
      higher. CONCLUSIONS: After their usual workday, radiologists experience increased
      fatigue and decreased diagnostic accuracy for detecting pulmonary nodules on CT.
      Effects of fatigue may be mitigated by active interaction with the display.

PMID- 22386168
TI  - An assessment of the feasibility and effectiveness of an e-learning module in
      delivering a curriculum in radiation protection to undergraduate medical
      students.
AB  - PURPOSE: Integrating radiation protection (RP) education in the undergraduate
      medical curriculum is gaining importance and is mandatory in certain
      jurisdictions. An e-learning module for RP was developed at the authors' medical
      school and was integrated into year 4 of the 5-year undergraduate medical
      program. The aim of this study was to investigate its impact on RP knowledge,
      student preferences for various teaching methods, self-assessment of RP
      knowledge, and perceptions of career prospects in radiology. Likert-type 5-point
      scale evaluations and general comments about the RP module and various methods of
      teaching were also obtained. METHODS: An e-learning module in RP was designed and
      presented to year 4 medical undergraduates. All students were required to
      complete premodule and postmodule questionnaires. RESULTS: Eighty-nine percent (n
      = 113) and 99% (n = 126) of the 127 medical students successfully completed and
      returned the premodule and postmodule questionnaires, respectively. After the e
      learning module, students' postmodule RP knowledge had improved significantly.
      Analysis of postmodule RP knowledge suggested that a favorable self-assessment of
      knowledge of RP, perception of career prospects in radiology, and completion of
      the e-learning module with an increased number of sessions were factors
      predictive of improved RP knowledge. Students expressed a preference for didactic
      lectures and clinical attachment for instruction in RP over e-learning.
      CONCLUSIONS: The development of an e-learning module in RP is feasible and
      results in improved knowledge of RP among medical undergraduates. Combining e
      learning and more traditional educational programs such as a clinical radiology
      rotation is likely to improve student experience.

PMID- 22386169
TI  - The implementation of the national breast screening program in the Maltese
      Islands.

PMID- 22386170
TI  - Securing medical radioisotopes from radiologic terrorism: lessons learned for a
      post-9/11 world.

PMID- 22386171
TI  - Establishing a strategic commercial partnership for an outpatient imaging
      center/not staying active clinically as an academic department chair.

PMID- 22386172
TI  - US contributions to international standards for medical electrical equipment.

PMID- 22386173
TI  - Wendell G. Scott.

PMID- 22386174
TI  - Oropharyngeal cancer biology and treatment: insights from messenger RNA sequence
      analysis and transoral robotic surgery.

PMID- 22386175
TI  - Opioid-abusing health care professionals: options for treatment and returning to
      work after treatment.

PMID- 22386176
TI  - Long-term functional and oncologic results of transoral robotic surgery for
      oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVE: To examine the long-term functional and oncologic results in patients
      who underwent transoral robotic surgery (TORS) as primary therapy or as part of
      combined therapy for oropharyngeal squamous cell carcinoma arising in the tonsil
      or base of tongue. PATIENTS AND METHODS: We reviewed a prospective TORS database
      of patients with squamous cell carcinoma arising in the tonsil or base of tongue
      treated between March 2007 and February 2009 to determine oncologic outcomes at
      24 months or more of follow-up. The presenting tumor stage, histopathologic
      factors, surgical margins, and adjuvant treatment extent were evaluated.
      Functional outcomes included gastrostomy tube dependence and tracheostomy
      dependence. Oncologic outcomes included local, regional, and distant control and
      disease-specific and recurrence-free survival. RESULTS: A total of 66 TORS
      patients were followed up for a minimum of 2 years. Most (97.0%; 64 of 66) were
      able to eat orally within 3 weeks after surgery before starting adjuvant therapy.
      Long-term gastrostomy tube use was required in 3 of the 66 (4.5%) and long-term
      tracheotomy in 1 (1.5%). Three-year estimated local control and regional control
      were 97.0% and 94.0%, respectively. Two-year disease-specific survival and
      recurrence-free survival were 95.1% and 92.4%, respectively. CONCLUSION: With
      appropriate adjuvant therapy, TORS achieves excellent functional results for
      patients with oropharyngeal squamous cell carcinoma. Oncologic outcomes are
      equivalent or superior to results of other surgical and nonsurgical treatments.

PMID- 22386177
TI  - Transcriptional profiling by sequencing of oropharyngeal cancer.
AB  - OBJECTIVE: To compare full transcriptome expression levels of matched tumor and
      normal samples from patients with oropharyngeal carcinoma stratified by known
      tumor etiologic factors. PATIENTS AND METHODS: Full transcriptome sequencing was
      analyzed for 10 matched tumor and normal tissue samples from patients with
      previously untreated oropharyngeal carcinoma. Transcriptomes were analyzed using
      massively parallel messenger RNA sequencing and validated using the NanoString
      nCounter system. Global gene expression levels were compared in samples grouped
      by smoking status and human papillomavirus status. This study was completed
      between June 10, 2010, and June 30, 2011. RESULTS: Global gene expression
      analysis indicated tumor tissue from former smokers grouped more closely to the
      never smokers than the current smokers. Pathway analysis revealed alterations in
      the expression of genes involved in the p53 DNA damage-repair pathway, including
      CHEK2 and ATR, which display patterns of increased expression that is associated
      with human papillomavirus-negative current smokers rather than former or never
      smokers. CONCLUSION: These findings support the application of messenger RNA
      sequencing technology as an important clinical tool for more accurately
      stratifying patients based on individual tumor biology with the goal of improving
      our understanding of tumor prognosis and treatment response, ultimately leading
      to individualized patient care strategies.

PMID- 22386178
TI  - Clinical findings and diagnosis in human granulocytic anaplasmosis: a case series
      from Massachusetts.
AB  - OBJECTIVE: To describe clinical findings and the use of a tick-associated
      pathogen panel in a series of patients with human granulocytic anaplasmosis (HGA)
      at a suburban Boston hospital. PATIENTS AND METHODS: Medical records were
      reviewed for inpatients and outpatients at Newton-Wellesley Hospital with a
      positive polymerase chain reaction (PCR) result for Anaplasma phagocytophilum
      during the study period March 1 through November 30, 2009. A PCR panel was used
      to test for tick-borne pathogens. Postal ZIP code data from the patients' areas
      of residence were used to estimate the area of disease transmission. RESULTS:
      Thirty-three cases were confirmed during the 2009 transmission season, and 14 of
      these patients (42%) required hospitalization. Thrombocytopenia and/or leukopenia
      were observed at the time of presentation in 25 of 30 patients (86%) in whom both
      white blood cell and platelet counts were determined, and 28 of 33 patients (85%)
      reported fever. Rash occurred in only 2 of the 33 patients (6%), and 25 (76%)
      reported one or more respiratory or gastrointestinal symptom. Cases were
      geographically distributed diffusely throughout the hospital catchment area, with
      one possible focus of infection identified in Weston, MA. Due to a lack of
      clinical data reporting to the Massachusetts Department of Public Health, only 20
      of 32 HGA cases (63%) fulfilled the case confirmation criteria. CONCLUSION:
      Diagnosis of HGA requires a high suspicion for infection even in endemic areas.
      Use of a tick-associated pathogen panel that includes PCR assays for several
      organisms could improve detection of underrecognized tick-borne diseases in
      endemic areas. Lack of epidemiological follow-up to confirm corroborating
      clinical findings prevents accurate case reporting and assessment of the true HGA
      burden.

PMID- 22386179
TI  - Germline predictors of androgen deprivation therapy response in advanced prostate
      cancer.
AB  - OBJECTIVE: To evaluate whether germline variations in genes involved in sex
      steroid biosynthesis and metabolic pathways predict time to treatment failure for
      patients with advanced prostate cancer undergoing androgen deprivation therapy
      (ADT), because there are few known clinical predictors of response. PATIENTS AND
      METHODS: In a cohort of 304 patients with advanced prostate cancer undergoing
      ADT, we genotyped 746 single-nucleotide polymorphisms (SNPs) from 72 genes from
      germline DNA (680 tagSNPs from 58 genes and 66 candidate SNPs from 20 genes [6
      genes common in both]). Association with the primary end point of time to ADT
      failure was assessed using proportional hazards regression models at the gene
      level (for genes with tagging SNPs) and at the SNP level. False discovery rates
      (FDRs) of 0.10 or less were considered noteworthy to account for multiple
      testing. RESULTS: At the gene level, TRMT11 showed the strongest association with
      time to ADT failure (P<.001; FDR=0.008). Two of 4 TRMT11 tagSNPs were associated
      with time to ADT failure. Median time to ADT failure for rs1268121 (A>G) was 3.05
      years for the AA, 4.27 years for the AG, and 6.22 years for the GG genotypes
      (P=.002), and for rs6900796 (G>A), it was 2.42 years for the GG, 3.52 years for
      the AG, and 4.18 years for the AA genotypes (P<.001). No other gene level or SNP
      level tests had an FDR of 0.10 or less. CONCLUSION: Genetic variation in TRMT11
      was associated with time to ADT failure. Confirmation of these preliminary
      findings in an independent cohort is needed.

PMID- 22386180
TI  - Prognostic value of cardiac troponin T after myocardial infarction: a
      contemporary community experience.
AB  - OBJECTIVE: To evaluate the role of cardiac troponin T (cTnT) in predicting death,
      recurrent ischemic events, and heart failure among community-dwelling persons
      with first myocardial infarction (MI). PATIENTS AND METHODS: Consecutive Olmsted
      County, Minnesota, residents with an incident MI between November 6, 2002, and
      December 31, 2007, were studied (N=1177; mean age, 68 years). Maximal cTnT value
      was measured at a median of 1 day after MI (median, 0.52 ng/mL; interquartile
      range, 0.16-1.75 ng/mL) and evaluated as a prognostic factor using measures of
      absolute risk. RESULTS: During a mean follow-up of 16 months, 276 deaths (23%)
      occurred, 341 patients (29%) experienced a recurrent ischemic event, and 326
      patients (28%) experienced heart failure. A dose-response relationship was
      demonstrated early after MI between cTnT and the adjusted cumulative incidence of
      all outcomes. The multivariate-adjusted absolute risk differences (events per 100
      patients) between the upper and lower cTnT tertiles at 30 days were 5.8 (95%
      confidence interval [CI], 1.4-10.2) for death, 5.2 (95% CI, 0.2-10.3) for
      recurrent ischemic event, and 6.9 (95% CI, 1.4-12.4) for heart failure. These
      differences were either maintained or increased at 2 years. CONCLUSION: In the
      community, cTnT level predicts death and nonfatal cardiac events independently of
      other prognostic factors. The increased risk associated with elevated cTnT level
      appears shortly after MI and persists for at least 2 years.

PMID- 22386181
TI  - Use of methylnaltrexone for the treatment of opioid-induced constipation in
      critical care patients.
AB  - Gastrointestinal dysmotility and constipation are common problems in critical
      care patients. The majority of critical care patients are treated with opioids,
      which inhibit gastrointestinal (GI) motility and lead to adverse outcomes. We
      reasoned that methylnaltrexone (MNTX), a peripheral opioid antagonist approved
      for the treatment of opioid-induced constipation in patients with advanced
      illness receiving palliative care when response to laxative therapy has not been
      sufficient, could improve GI function in critically ill patients. The present
      study included all patients in our intensive care unit who required rescue
      medication for GI stasis during the 10-week period from September 1 to November
      15, 2009. We compared conventional rescue therapy with subcutaneous MNTX. We
      performed a retrospective chart review of the 88 nonsurgical critical care
      patients receiving fentanyl infusions, 15 (17%) of whom met the criteria of
      absence of laxation within 72 hours of intensive care unit admission despite
      treatment with senna and sodium docusate. Eight of these 15 patients subsequently
      received conventional rescue therapy (combination of sodium picosulfate [5 mg]
      and 2 glycerin suppositories [4-g mold]), and 7 patients received MNTX
      (subcutaneous injection, 0.15 mg/kg). Laxation occurred within 24 hours in 6 of
      the 7 MNTX patients (86%) but in none of the 8 patients receiving conventional
      rescue therapy (P=.001). The median difference in time to laxation between the 2
      groups was 3.5 days (P<.001). Although not statistically significant, all 7
      patients treated with MNTX, but only 4 of 8 (50%) who received conventional
      rescue therapy, progressed to full target enteral feeding (P=.08). Intensive care
      unit mortality was 2 of 7 MNTX patients (29%) vs 4 of 8 (50%) in the standard
      therapy group (P=.61). We hypothesize that MNTX may play an important role in
      restoration of bowel function in critically ill patients.

PMID- 22386182
TI  - Buprenorphine maintenance therapy in opioid-addicted health care professionals
      returning to clinical practice: a hidden controversy.
AB  - It remains controversial whether it is safe for recovering health care
      professionals to return to clinical practice after treatment for drug addiction.
      One specific component of reentry that remains particularly contentious is the
      use of pharmacotherapeutics, specifically buprenorphine, as opioid substitution
      therapy for health care professionals who wish to return to clinical work.
      Because health care professionals are typically engaged in safety-sensitive work
      with considerable consequences when errors occur, abstinence-based recovery
      should be recommended until studies demonstrate that it is safe to allow this
      population to practice while undergoing opioid substitution therapy.

PMID- 22386183
TI  - Clinical pearls in neurology.

PMID- 22386184
TI  - 54-year-old man with severe prostatism, palatal mass, and history of
      pancreatitis.

PMID- 22386187
TI  - ST elevation anterior "spiked helmet" sign.

PMID- 22386188
TI  - Dysphagia lusoria.

PMID- 22386185
TI  - Current concepts in laboratory testing to guide antimicrobial therapy.
AB  - Antimicrobial susceptibility testing (AST) is indicated for pathogens
      contributing to an infectious process that warrants antimicrobial therapy if
      susceptibility to antimicrobials cannot be predicted reliably based on knowledge
      of their identity. Such tests are most frequently used when the etiologic agents
      are members of species capable of demonstrating resistance to commonly prescribed
      antibiotics. Some organisms have predictable susceptibility to antimicrobial
      agents (ie, Streptococcus pyogenes to penicillin), and empirical therapy for
      these organisms is typically used. Therefore, AST for such pathogens is seldom
      required or performed. In addition, AST is valuable in evaluating the activity of
      new and experimental compounds and investigating the epidemiology of
      antimicrobial resistant pathogens. Several laboratory methods are available to
      characterize the in vitro susceptibility of bacteria to antimicrobial agents.
      When the nature of the infection is unclear and the culture yields mixed growth
      or usual microbiota (wherein the isolates usually bear little relationship to the
      actual infectious process), AST is usually unnecessary and results may, in fact,
      be dangerously misleading. Phenotypic methods for detection of specific
      antimicrobial resistance mechanisms are increasingly being used to complement AST
      (ie, inducible clindamycin resistance among several gram-positive bacteria) and
      to provide clinicians with preliminary direction for antibiotic selection pending
      results generated from standardized AST (ie, beta-lactamase tests). In addition,
      molecular methods are being developed and incorporated by microbiology
      laboratories into resistance detection algorithms for rapid, sensitive assessment
      of carriage states of epidemiologically and clinically important pathogens, often
      directly from clinical specimens (ie, presence of vancomycin-resistant
      enterococci in fecal specimens).

PMID- 22386189
TI  - Alexander Todd--British Nobel laureate.

PMID- 22386191
TI  - How best to use our tools?

PMID- 22386192
TI  - Re: Vincenzo Pagliarulo, Sergio Bracarda, Mario A. Eisenberger, et al.
      Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol
      2012;61:11-25.

PMID- 22386193
TI  - Concordance of tumor differentiation among brothers with prostate cancer.
AB  - BACKGROUND: Genetic factors seem to be of greater importance in prostate cancer
      than in other forms of cancer. Studies have suggested familial concordance in
      survival, but the extent to which that is due to tumor characteristics is not
      known. OBJECTIVE: We hypothesized that a brother of an index case with prostate
      cancer is at particularly increased risk of prostate cancer with the same tumor
      differentiation as the index case. DESIGN, SETTING AND PARTICIPANTS: We
      identified 21,930 brothers of index cases with prostate cancer in the Prostate
      Cancer Data Base Sweden and followed them up for incidence of prostate cancer.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The relative risk of Gleason score
      specific prostate cancer in the cohort of brothers was estimated by using the
      standardized incidence ratio (SIR) stratified by Gleason score of the index case.
      We estimated 95% confidence intervals (CIs) assuming a Poisson distribution.
      RESULTS AND LIMITATIONS: Among brothers of index cases with Gleason score 8-10
      cancer, the SIR was 2.53 (95% CI, 1.97-3.21) for a Gleason score 2-6 cancer and
      4.00 (95% CI, 2.63-5.82) for a Gleason score 8-10 cancer. SIR for Gleason score 2
      6 cancer among brothers decreased with time since the date of the index cases'
      diagnoses, whereas the risk of Gleason 8-10 cancer increased over time for
      brothers of index cases with Gleason 8-10 cancer (p for trend = 0.009).
      CONCLUSIONS: Brothers of men with high-grade prostate cancer are at particularly
      increased risk of high-grade prostate cancer. Likewise, there is a concordance of
      less malignant prostate cancers within families. These findings may have direct
      clinical relevance for counseling men with a family history of prostate cancer.

PMID- 22386195
TI  - Serum levels of microRNAs miR-371-3: a novel class of serum biomarkers for
      testicular germ cell tumors?

PMID- 22386196
TI  - Treatment of postprostatectomy male urinary incontinence with the transobturator
      retroluminal repositioning sling suspension: 3-year follow-up.
AB  - BACKGROUND: The AdVance male sling (American Medical Systems, Minnetonka, MN,
      USA) has been shown to be an efficacious device in short-term studies for
      postprostatectomy incontinence (PPI), but long-term studies are lacking.
      OBJECTIVE: Examine the intermediate-term outcome with the AdVance sling for PPI
      management. DESIGN, SETTING, AND PARTICIPANTS: A multicentre prospective
      evaluation was conducted on consecutive patients treated for PPI in three
      European tertiary reference centres. INTERVENTION: Patients were implanted with
      the AdVance male sling with no associated surgery. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Measurements included daily pad usage, maximum flow rate
      (Qmax), postvoid residual urine (PVR), the International Consultation on
      Incontinence Questionnaire-Short Form, the Incontinence Quality of Life
      questionnaires, and complications of surgery. Paired Wilcoxon signed rank test
      univariable and multivariable analyses were used. RESULTS AND LIMITATIONS: Follow
      up was available for 156 patients for the majority of parameters. Pad usage was
      significantly decreased compared with baseline at 12 mo and 3 yr (p<0.0001). At
      12 mo, 76.9% of patients could be classified as cured or improved; this
      percentage was maintained at 3 yr (76.8%). Cure rates (58.6% vs 42.3%) and
      improvement rates (23.2% vs 25.0%) were higher in patients with mild or moderate
      incontinence compared with severe incontinence. Univariable analysis showed that
      pretreatment pad usage and severity of incontinence were both significant
      predictors of success (p=0.0355 and p=0.0420, respectively). However, in
      multivariable analysis, only pad usage was an independent predictor of success.
      There were no perioperative or severe postoperative complications. Most
      complications were Dindo grade I. Seven patients required a second treatment for
      stress urinary incontinence. There was no worsening over time. Limitations of
      this study included no comparator group, quality of life questionnaires in only
      two centres, and no 24-h pad test. CONCLUSIONS: The transobturator retroluminal
      repositioning sling suspension is effective and safe in the longer term for
      treating PPI.

PMID- 22386197
TI  - Tension-free vaginal tape and beyond: our challenges and the future of anti
      incontinence therapy.

PMID- 22386199
TI  - A methodology to assess the energetic valorization of bio-based polymers from the
      packaging industry: pyrolysis of reprocessed polylactide.
AB  - The energetic valorization process of bio-based polymers is addressed in this
      study, taking polylactide (PLA) as model. The pyrolysis of virgin and multiple
      injected PLA was simulated by means of multi-rate linear-non-isothermal
      thermogravimetric experiments. A complete methodology, involving control of
      gases, thermal stability and thermal decomposition kinetics was proposed. The
      release of gases was monitored by Evolved Gas Analysis of the fumes of pyrolysis,
      by in-line FT-IR, with the aid of 2D-correlation IR characterization. A novel
      model to establish the thermal stability of PLAs under any linear heating profile
      was proposed. A kinetic strategy was methodically applied to assess the thermal
      decomposition in terms of activation energy and kinetic model. It was found that
      the pyrolysis technologies for virgin PLA could be straightforwardly transferred
      for the valorization of its recyclates.

PMID- 22386198
TI  - Peripheral innate immune challenge exaggerated microglia activation, increased
      the number of inflammatory CNS macrophages, and prolonged social withdrawal in
      socially defeated mice.
AB  - Repeated social defeat (RSD) activates neuroendocrine pathways that have a
      significant influence on immunity and behavior. Previous studies from our lab
      indicate that RSD enhances the inflammatory capacity of CD11b+ cells in the brain
      and promotes anxiety-like behavior in an interleukin (IL)-1 and beta-adrenergic
      receptor-dependent manner. The purpose of this study was to determine the degree
      to which mice subjected to RSD were more responsive to a secondary immune
      challenge. Therefore, RSD or control (HCC) mice were injected with saline or
      lipopolysaccharide (LPS) and activation of brain CD11b+ cells and behavioral
      responses were determined. Peripheral LPS (0.5 mg/kg) injection caused an
      extended sickness response with exaggerated weight loss and prolonged social
      withdrawal in socially defeated mice. LPS injection also amplified mRNA
      expression of IL-1beta, tumor necrosis factor (TNF)-alpha, inducible nitric oxide
      synthase (iNOS), and CD14 in enriched CD11b+ cells isolated from socially
      defeated mice. In addition, IL-1beta mRNA levels in enriched CD11b+ cells
      remained elevated in socially defeated mice 24 h and 72 h after LPS. Moreover,
      microglia and CNS macrophages isolated from socially defeated mice had the
      highest CD14 expression after LPS injection. Both social defeat and LPS injection
      increased the percentage of CD11b+/CD45(high) macrophages in the brain and the
      number of inflammatory macrophages (CD11b+/CD45(high)/CCR2+) was highest in RSD
      LPS mice. Anxiety-like behavior was increased by social defeat, but was not
      exacerbated by the LPS challenge. Nonetheless, reduced locomotor activity and
      increased social withdrawal were still present in socially defeated mice 72 h
      after LPS. Last, LPS-induced microglia activation was most evident in the
      hippocampus of socially defeated mice. Taken together, these findings demonstrate
      that repeated social defeat enhanced the neuroinflammatory response and caused
      prolonged sickness following innate immune challenge.

PMID- 22386200
TI  - Effect of C/N ratio and ammonia-N accumulation in a pilot-scale thermophilic dry
      anaerobic digester.
AB  - The effect of ammonia-N accumulation in a dry anaerobic digestion was studied
      effectively using pilot-scale thermophilic reactor. Two simulations were prepared
      to attain C/N ratio 27 and C/N ratio 32 using bio-degradable feedstocks such as
      food waste, fruit and vegetable waste, green waste and paper waste. Organic
      loading rates and digestate recirculation rates were varied during different time
      intervals and the performance was evaluated using parameters like pH, VFA,
      Alkalinity, ammonia-N and biogas yield. Results showed that the simulation with
      C/N ratio 32 had about 30% less ammonia in digestate as compared to that with C/N
      ratio 27. The system performed well up to organic loading rate (OLR) 7-10
      kgVS/m(3)d and retention time up to 19 days, with surplus energy production of 50
      73%. Moreover, a free ammonia accumulation/inhibition effect was documented and
      methods to overcome the adverse effects were discussed.

PMID- 22386201
TI  - Effect of steam explosion and enzymatic pre-treatments on pulping and bleaching
      of Hesperaloe funifera.
AB  - A non-wood raw material with high potential for pulp and paper applications
      (Hesperaloe funifera) was subjected to a steam explosion pre-treatment, and the
      subsequent effect of this pretreatment on biopulping and biobleaching was
      studied. An increase in the delignification rate, bigger than that reported for
      autohydrolysis and acid hydrolysis pre-treatments, and a reduction in chemical
      consumption were found during kraft pulping of the exploded samples. However,
      biopulping with the laccase-mediator system (LMS) did not lead to a reduction in
      the kappa number in either non-exploded or exploded unbleached pulps. On the
      other hand, the steam explosion pretreatment boosted the advantages of the LMS
      pre-treatment (decrease in kappa number and increase in brightness) favored
      biobleaching, with a 53.1% delignification rate and a final brightness of 67%
      ISO. Finally, the steam explosion pre-treatment also improved the color
      properties of the bleached pulp and reduced the hydrogen peroxide consumption by
      24.6%.

PMID- 22386202
TI  - Torrefied biomasses in a drop tube furnace to evaluate their utility in blast
      furnaces.
AB  - Torrefaction and burning characteristics of bamboo, oil palm, rice husk, bagasse,
      and Madagascar almond were studied and compared with a high-volatile bituminous
      coal using a drop tube furnace to evaluate the potential of biomass consumed in
      blast furnaces. Torrefaction at 250 and 300 degrees C for 1h duration was carried
      out. Analysis using the ash tracer method indicated that the extent of atomic
      carbon reduction in the biomasses was less than that of atomic hydrogen and
      oxygen. Torrefaction also lowered the sulfur content in bamboo and oil palm over
      33%. An examination of the R-factor and burnout of the samples suggests that more
      volatiles were released and a higher burnout was achieved with raw and torrefied
      biomasses at 250 degrees C than at 300 degrees C; however, torrefaction at 300
      degrees C is a feasible operating condition to transform biomass into a solid
      fuel resembling a high-volatile bituminous coal used for blast furnaces.

PMID- 22386203
TI  - Adsorption of nanoparticles at the solid-liquid interface.
AB  - The adsorption of differently charged nanoparticles at liquid-solid interfaces
      was investigated by in situ X-ray reflectivity measurements. The layer formation
      of positively charged maghemite (gamma-Fe(2)O(3)) nanoparticles at the aqueous
      solution-SiO(2) interface was observed while negatively charged gold
      nanoparticles show no adsorption at this interface. Thus, the electrostatic
      interaction between the particles and the charged surface was determined as the
      driving force for the adsorption process. The data analysis shows that a
      logarithmic particle size distribution describes the density profile of the thin
      adsorbed maghemite layer. The size distribution in the nanoparticle solution
      determined by small angle X-ray scattering shows an average particle size which
      is similar to that found for the adsorbed film. The formed magehemite film
      exhibits a rather high stability.

PMID- 22386204
TI  - Interactions between GaO4Al12(OH)24(H2O)12(7+) and cellulosic materials.
AB  - The adsorption qualities of GaO(4)Al(12)(OH)(24)(H(2)O)(12)(7+), a polycation
      with epsilon-Keggin structure, and its stability in contact with anionic
      cellulosic materials, was investigated under different concentration and ionic
      strength conditions. The cellulosic materials employed were two different fully
      bleached fibre materials, carboxyl methyl cellulose (CMC), and a spin-coated
      cellulose model surface. As analytical techniques, pH-measurements,
      potentiometric titrations, ICP-OES, QCM-D, equilibrium calculations and Extended
      X-ray Absorption Fine Structure (EXAFS) were used. The adsorption is substantial
      and the addition of GaO(4)Al(12)(OH)(24)(H(2)O)(12)(7+) to a fibre suspension
      results in a rapid decrease in pH, followed by a small and slow increase in pH.
      This behaviour can be explained as due to a rapid and strong (log beta>2)
      equilibrium adsorption of intact GaO(4)Al(12)(OH)(24)(H(2)O)(12)(7+) ions,
      followed by a slow, and minor, 3-8%, decomposition into different monomers.
      Alternative layer by layer adsorption of this ion, and CMC, on a spin-coated
      cellulose model surface constitutes further evidence for the strong interactions
      between the anionic cellulose materials and GaO(4)Al(12)(OH)(24)(H(2)O)(12)(7+).
      It is shown that the adsorption observed could not be described as due to an
      unspecific Donnan adsorption behaviour, neither of
      GaO(4)Al(12)(OH)(24)(H(2)O)(12)(7+) nor Ga and Al monomers, and specific surface
      complex formation is therefore discussed and applied. The
      (=COO)(7)GaO(4)Al(12)(OH)(24)(H(2)O)(12) species found to explain the pH- and
      metal adsorption data should be considered strictly as a stoichiometric entity.

PMID- 22386205
TI  - Electrochemical characterization of self-assembled monolayers (SAMs) of silanes
      on indium tin oxide (ITO) electrodes--tuning electron transfer behaviour across
      electrode-electrolyte interface.
AB  - In this work, we have systematically investigated the formation and
      characterization of Self-assembled Monolayer (SAM) films of several silanes on
      indium tin oxide (ITO) surfaces. Silane molecules having different domains namely
      substrate binding domain (siloxanes), electron transport region (aliphatic and
      aromatic spacer) and terminal functional groups (-SH, -CH(3) groups) are employed
      for the study in order to tune the electron transfer (ET) behaviour across SAM
      modified electrode-electrolyte interface. Structural characterization of these
      monolayer films is carried out using X-ray photoelectron spectroscopy (XPS)
      studies. Wettability (hydrophilic and hydrophobic nature) of such modified
      electrodes is evaluated using contact angle measurements. ET behaviour of these
      modified electrodes is investigated by electrochemical techniques namely cyclic
      voltammetry (CV) and electrochemical impedance spectroscopy (EIS) using
      K(4)Fe(II)(CN)(6)|K(3)Fe(III)(CN)(6) redox couple as a probe. Disappearance of
      redox peaks in the CV measurements and formation of semicircle having a higher
      charge transfer resistance (R(ct)) values during EIS studies suggest that the
      resultant monolayer films are compact, highly ordered with very low defects and
      posses good blocking property with less pinholes. The heterogeneous ET rate
      constant (k) values are determined from EIS by fitting them to an appropriate
      equivalent circuit model. Based on our results, we comment on tuning the ET
      behaviour across the interface by a proper choice of spacer region.

PMID- 22386206
TI  - NR2C and NR2D subunits of NMDA receptors in frog and turtle retina.
AB  - Glutamate NMDA (N-methyl-D-aspartate) receptors are widely distributed in the
      central nervous system where they are involved in cognitive processes, motor
      control and many other functions. They are also well studied in the retina, which
      may be regarded as a biological model of the nervous system. However, little is
      known about NR2C and NR2D subunits of NMDA receptors, which have some specific
      features as compared to other subunits. Consequently the aim of the present study
      was to investigate their distribution in frog (Rana ridibunda) and turtle (Emys
      orbicularis) retinas which possess mixed and cone types of retina respectively.
      The experiments were performed using an indirect immunofluorescence method. Four
      antibodies directed to NR2C and NR2D subunits of NMDA receptor, as well as three
      antibodies directed to different splice variants of NR1 subunit, which is known
      to be obligatory for proper functioning of the receptor, were applied. All
      antibodies caused well expressed labeling in frog and turtle retinas. The NR2C
      and NR2D subunits were localized in glial Muller cells, while the NR1 subunit had
      both neuronal and glial localization. Our results show that glial NMDA receptors
      differ from neuronal ones in their subunit composition. The functional
      significance of the NMDA receptors and their NR2C and NR2D subunits, in
      particular for the neuron-glia interactions, is discussed.

PMID- 22386207
TI  - [Assessment of multiple morbidity in people of advanced age. An important area of
      integral geriatric assessment].

PMID- 22386208
TI  - New monolithic chromatographic supports for macromolecules immobilization:
      challenges and opportunities.
AB  - This mini-review reports on some recent advances in the field of immobilized
      protein employing both silica and polymer-based monoliths as supports, and their
      application in affinity chromatography and immobilized enzyme reactors (IMERs)
      developments. The major emphasis is put on some interesting challenges and
      opportunities related to the development of new monolithic affinity supports
      based on biofriendly sol-gel inorganic monoliths with entrapped proteins and on
      organic monolithic supports with improved hydrophilicity for IMERs development in
      proteomic studies. The ease of preparation of monoliths and the multitude of
      functionalization techniques, make monoliths interesting for an increasing number
      of biochemical and medical applications.

PMID- 22386209
TI  - Development and validation of non-aqueous capillary electrophoresis methods to
      analyze boronic esters and acids.
AB  - Boronic esters and acids are potential intermediates in the manufacture of many
      active pharmaceutical ingredients (API). Accurate quantitation of the
      intermediate is necessary to assure the stoichiometry of the reaction. The
      analysis of these compounds is challenging due to their labile nature. For
      example, the boronic ester can hydrolyze to the acid during storage, when exposed
      to moisture in the air, during sample preparation and analysis, and thus give
      erroneous ester results. Traditional analytical techniques like gas
      chromatography (GC), normal phase chromatography (NPLC), hydrophilic interaction
      chromatography (HILIC), and reversed phase liquid chromatography (RPLC) have been
      utilized but with noted limitations such as poor peak shape, variation in
      retention times, and evidence of hydrolysis. All of these limitations impact
      accurate quantitation needed for selected situations. For the proprietary boronic
      ester evaluated here, these traditional techniques were insufficient for the
      accurate determination of assay and residual boronic acid. Non-aqueous capillary
      electrophoresis (NACE) is an accurate quantitative technique that can be used to
      analyze boronic esters and their corresponding acids without the limitations
      noted for traditional analytical techniques. The present study describes the
      development of methodology for the determination of the potency of a proprietary
      boronic ester as well as methodology for the determination of residual boronic
      acid in the ester. In addition, nine model boronic ester and acid pairs with a
      range in polarity, based on the electronic properties of the attached side group,
      were tested to evaluate and demonstrate the general applicability of these
      conditions. Under the conditions used for potency, all ten pairs had a resolution
      between the boronic ester and acid of greater than 1.5, acceptable peak shape for
      the boronic ester (tailing factor of less than 2.0), and a run time of less than
      3 min. In addition, this work describes the development of methodology to
      determine residual levels of boronic acids in the corresponding boronic ester.
      Using the ten boronic ester and acid pairs, eight of the ten pairs were shown to
      have acceptable sensitivity (S/N of 10 or better at 0.5%) and spike recoveries
      (within the range of 80-120%). The potential for hydrolysis during analysis was
      also addressed by using a subset of the ten boronic ester and acid pairs and
      spiking water into the diluent. There was no observed conversion of the ester to
      the acid. The lack of hydrolysis during analysis and the high success in
      separating and validating these methods for the boronic ester and acid pairs
      supports the utility of NACE as a technique for the analysis of boronic esters
      and acids.

PMID- 22386210
TI  - HPLC analysis of naturally occurring free D-amino acids in mammals.
AB  - D-amino acids are currently recognized as naturally occurring physiologically
      active substances and biomarkers in mammals. The progress of analytical
      technologies, mostly high resolution chromatographic or electrodriven separation
      methods, has significantly contributed to the advances in D-amino acid research
      in real biological matrices. In this review, we would like to describe the D
      amino acid research, from the discovery of appreciable amounts of free D-amino
      acids in mammals to the current metabolomics study focusing on amino acid
      enantiomers. The liquid phase enantioselective analytical methods utilized for
      the determination of D-amino acids in mammals including human beings will be
      discussed.

PMID- 22386211
TI  - Development and validation of an alpha fetoprotein immunoassay using Gyros
      technology.
AB  - Circulating alpha fetoprotein (AFP) is a diagnostic and prognostic biomarker for
      hepatocellular carcinoma (HCC) with potential utility as a pharmacodynamic
      endpoint in rodent tumor models. This application is limited, however, by low
      sample volumes, highlighting the need for sensitive, sample-sparing biomarker
      assay methods. In order to improve the utility of AFP as an oncology biomarker,
      we developed a method for AFP using the GyrolabTM, an automated microimmunoassay
      platform. Commercially available antibodies were screened to identify optimal
      combinations that were then used in a multi-factorial design of experiments (DOE)
      to optimize reaction conditions. Analytical validation included assessments of
      accuracy and precision (A&P), and dilutional linearity/hook effect, as well as
      reagent and sample stability. The method is reliable, with total error, a measure
      of accuracy and precision, less than 30% for all concentrations tested. AFP
      concentrations were measurable in diseased mice and undetectable in normal mice.
      Therefore, this novel, low volume AFP immunoassay is suitable for pre-clinical
      drug development, where its miniaturized format facilitates serial sampling in
      rodent models of cancer.

PMID- 22386212
TI  - Curve walking is not better than straight walking in estimating ambulation
      related domains after incomplete spinal cord injury.
AB  - OBJECTIVES: To investigate whether a figure-of-8-shaped walking test can estimate
      various domains of walking in subjects with incomplete spinal cord injury (iSCI)
      better than the 10-meter walk test (10MWT), and to explore similarities and
      differences between the 2 tests and between subjects with iSCI and age-matched,
      healthy controls. DESIGN: Case-control study. SETTING: Spinal cord injury center
      of a university hospital. PARTICIPANTS: A convenience sample of subjects with
      iSCI (n=15; mean age, 50y; 40% women; neurologic level from C3 to L5; median time
      since injury, 5mo) was compared with an age-matched control group (47% women).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The figure-of-8 test (FET)
      included 6 conditions to test the subjects' ability to adapt their gait to
      several circumstances. These conditions covered normal and maximal walking speed,
      constrained vision, obstacles, foamed soles, and a dual task. Additionally,
      subjects were tested for lower extremity muscle strength, gait capacity (10MWT)
      and balance, independence, and fear of falling. RESULTS: (1) Preferred straight
      walking speed correlated with the different FET conditions in both groups; (2) if
      normalized to preferred straight-walking speed, FET conditions showed significant
      differences between both groups; (3) if normalized to preferred curve-walking
      speed, these differences seemed to disappear; and (4) the 10MWT appeared superior
      to the different conditions of the FET in estimating various walking-related
      functions. CONCLUSIONS: Subjects with iSCI seem to have difficulties with curve
      walking compared with straight walking. We therefore recommend the implementation
      of curve walking into rehabilitation training programs. However, the FET did not
      provide a better estimate of functional ambulation performance after an iSCI
      compared with the 10MWT.

PMID- 22386213
TI  - Six patient-reported outcome measurement information system short form measures
      have negligible age- or diagnosis-related differential item functioning in
      individuals with disabilities.
AB  - OBJECTIVE: To evaluate the measurement invariance of 6 self-report measures
      selected for an ongoing longitudinal study of individuals with spinal cord
      injury, muscular dystrophy, postpolio syndrome, and multiple sclerosis. DESIGN:
      Participants completed and returned by mail surveys that included the targeted
      self-report measures. Ordinal logistic regressions methods were applied to
      evaluate items for differential item functioning (DIF) by diagnosis and age
      range. SETTING: Community. PARTICIPANTS: Participants (N=2479) who had 1 of the 4
      target diagnoses. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Six short-form
      measures from the Patient-Reported Outcome Measurement Information System
      (PROMIS) were administered to participants to measure fatigue, pain interference,
      satisfaction with social roles, sleep disturbance, sleep-related impairment, and
      depression. RESULTS: One item of 1 measure (fatigue) exhibited DIF by diagnosis
      based on a published standard for meaningful DIF. However, scores corrected for
      this DIF were highly correlated with uncorrected scores (r>.999). No DIF by age
      range was found for any of the measures. CONCLUSIONS: Study findings support the
      use of the selected PROMIS short forms for comparing symptoms and quality of life
      indicators across different diagnoses and age ranges.

PMID- 22386214
TI  - Monostotic Paget's disease involving the calcaneus encountered incidentally on
      bone scintigraphy.
AB  - Isolated involvement of calcaneus with Paget's disease of bone is highly unusual,
      with very few cases reported in the world literature. We present herein a unique
      69-year-old male patient with monostotic Paget's disease of the left calcaneus
      discovered incidentally during a whole body bone scintigraphy. Since most bone
      scans are performed for evaluating osseous metastases, differentiating Paget's
      disease from overlapping metastases may be of significant clinical value. We
      discuss further the importance of whole body bone scan and other imaging
      modalities in establishing the correct diagnoses in such cases.

PMID- 22386215
TI  - The effect of the use of a walkway and the choice of the foot on plantar pressure
      assessment when using pressure platforms.
AB  - BACKGROUND: Plantar pressure assessment is routinely used in a clinical setting
      for diagnosing foot problems and prescribing orthoses or footwear. Despite this,
      the measurement procedures and protocols that might have an effect on the results
      are not standardised. OBJECTIVE: The purpose of this study was to evaluate, if
      variations in the data collection protocol such as the use of a walkway and
      stepping preference influence the measured plantar pressure parameters. METHOD:
      21 participants who were recruited from a convenience sample and consented to
      participate were tested under a number of different conditions through which the
      effect of these variations was tested. A paired T-test was used to determine
      whether a significant difference in the data corresponding to each subject for
      different testing conditions existed. RESULTS: Although there were significant
      differences between the plantar pressure measurement with the choice of the foot,
      there were no significant difference in the majority of plantar pressure
      parameters whilst using or not using the walkway. CONCLUSION: The results suggest
      that in a clinical and research setting extrinsic factors such as stepping
      preference needs to be considered to eliminate the effect of variability in
      plantar pressure data.

PMID- 22386216
TI  - The effect of aging on the hardness of foot sole skin: a preliminary study.
AB  - BACKGROUND: Foot problems are common in older people and altered biomechanical
      parameters under the foot sole has been proposed as a key risk factor for foot
      lesions. Therefore the aim of this study was to investigate the age-related
      differences in the hardness of foot sole skin. METHODS: Twenty-six healthy
      volunteers without foot problems, aged from 26 to 65 years, were examined using
      shore meter. The hardness of the foot sole under the big toe (area 8), 1st
      metatarsal head (area 5), 3rd metatarsal head (area 6), 5th metatarsal head (area
      7), mid foot (area 3, 4) and hind foot (area 1, 2) were measured. The correlation
      between age and hardness of foot sole was examined and comparisons were made
      between two age groups. RESULTS: From the result we observe statistical
      significant (p<0.05; p<0.01; p<0.005) differences in hardness between age groups
      in hind foot, metatarsal heads (1st, 3rd & 5th) and big toe. Strong positive
      correlations between age and hardness of the foot sole were found at the big toe
      (r=0.57; p<0.005), 1st metatarsal head (r=0.567; p<0.00001), 3rd metatarsal head
      (r=0.565; p<0.00001), 5th metatarsal head (r=0.55; p<0.00001), and heel (r=0.59;
      p<0.0001). CONCLUSION: The loss of compliance in the foot sole may be one of the
      factors responsible for the higher incidence of foot problems in aged people.
      Routine foot examination and appropriate therapeutic intervention including the
      use of foot orthoses and optimal hardness of foot wear insole may help to prevent
      the serious foot injuries.

PMID- 22386217
TI  - Identification of a novel PRRT2 mutation in patients with paroxysmal kinesigenic
      dyskinesias and c.649dupC as a mutation hot-spot.

PMID- 22386218
TI  - Psychological correlates in patients with different levels of hypertension.
AB  - The evidence linking essential systemic arterial hypertension (SAH) with
      psychological characteristics remains equivocal. The aims of this study were to
      assess clinical and subclinical distress, psychosocial aspects and psychological
      well-being in treated hypertensive patients and to evaluate the psychosocial
      variables associated with higher levels of blood pressure according to guidelines
      for hypertension management. A consecutive series of 125 hypertensive patients
      were evaluated using both self- and observer-rated reliable measures. Generalized
      anxiety disorder, minor depression, demoralization and alexithymia were the most
      frequent diagnoses. Cluster analysis revealed an association of three distinct
      symptomatological groups such as the Anxiety-Depression, the Alexithymia and the
      Somatization groups, with different levels of hypertension. In particular,
      patients with moderate to severe hypertension were more frequently in the Anxiety
      Depression and the Alexithymia groups, whereas the Somatization cluster has been
      shown to be associated with isolated systolic hypertension. The results provide
      new insight into the psychosocial characteristics among patients with different
      levels of SAH according to recent guidelines of the management of hypertension.
      They also outline the need to monitor the clinical course of hypertensive
      patients characterized by these specific clinical and subclinical psychological
      conditions.

PMID- 22386219
TI  - Motor impairment in children with anxiety disorders.
AB  - This study examined the frequency and degree of motor impairment in referred
      children with anxiety disorders (AnxDs), compared with children with attention
      deficit/hyperactivity disorder (ADHD), children with comorbid AnxDs and ADHD, and
      nonreferred controls. All participants (n=141; 90 males, 51 females; mean age: 10
      years, 1 month; range: 7-13 years) had an IQ greater than 70. Diagnoses of mental
      disorders were established using the Schedule for Affective Disorders and
      Schizophrenia for School-Aged Children (Kiddie-SADS). Motor ability was assessed
      using the Movement Assessment Battery for Children (M-ABC). We found that
      children with AnxDs exhibited significantly higher total impairment scores on the
      M-ABC than controls, but were not significantly different from children with ADHD
      or children with comorbid AnxDs and ADHD. All clinical groups exhibited similar
      profiles of motor impairment. A total of 19 (46%) children with AnxDs scored
      below the 5th percentile on the M-ABC, indicating that motor function is impaired
      in many children with AnxDs to a degree that probably interferes with their
      activities of daily living. These results support the notion that assessment of
      motor function is important in understanding the daily challenges of children
      with AnxDs.

PMID- 22386220
TI  - Symptom overlap in posttraumatic stress disorder and major depression.
AB  - Over the past decade there has been consistent criticism of the diagnostic
      criteria of posttraumatic stress disorder (PTSD) because of its high comorbidity
      with other mental disorders. Part of the problem surrounding PTSD may be related
      to the heterogeneity of its symptoms. In fact, recent research has identified a
      subset of PTSD symptoms, including symptoms of numbing and dysphoria, that may
      explain much of the overlap between PTSD and major depressive disorder (MDD). The
      present study sought to extend prior work by investigating the various subsets of
      PTSD symptoms in individuals from all four diagnostic combinations of PTSD and
      MDD (no MDD-PTSD, MDD-only, PTSD-only, and comorbid MDD-PTSD). Consenting
      participants completed diagnostic interviews and were categorized into the four
      groups. Based on responses to a self-report measure of PTSD symptoms,
      participants with no MDD-PTSD reported the least severe symptoms while the
      participants with comorbid MDD-PTSD reported the most severe symptoms.
      Interesting, participants in the MDD-only and PTSD-only groups consistently
      reported similar scores across all PTSD symptom scales. These findings further
      highlight the problematic diagnostic criteria and comorbidity in PTSD and
      emphasize the need to incorporate transdiagnostic treatment practices that focus
      on the overlapping symptoms, rather than specific diagnostic categories.

PMID- 22386221
TI  - Impact of red blood cells transfusion on ICU-acquired bloodstream infections: a
      case-control study.
AB  - Our study investigated the impact of packed red blood cell (pRBC) transfusion on
      the occurrence of bloodstream infections (BSIs) in patients admitted in a
      multidisciplinary intensive care unit (ICU), further assessing potential
      associations with particular BSI types. A nested matched (1:1) case-control
      design was implemented. Sex, age, admission category, Acute Physiology and
      Chronic Health Evaluation score II (plus Injury Severity Score in trauma
      patients) were used for matching. Controls were selected to have an ICU length of
      stay at least equal to the time to first BSI episode of the corresponding cases.
      Propensity scores for receiving pRBC transfusion were calculated in the entire
      prospective cohort. Of 582consecutive ICU patients, 165 matched case-control
      pairs were formed. In multivariable analysis, pRBC transfusion was independently
      associated with 2-fold probability for BSI (adjusting for matching variables and
      propensity score). There was a significant dose-dependent association of BSI risk
      with regard to the number of pRBC units transfused (odds ratios [OR], 1.73, 2.09,
      2.34 for 1-3, 4-6, and more than 6 pRBC units transfused, respectively, compared
      with nontransfused patients, P values .116, .018, and .015, respectively). In
      subgroup analysis, catheter-related BSIs displayed the strongest association with
      pRBC transfusion (OR = 5.01, P = .014).

PMID- 22386222
TI  - Impact of a multidimensional approach on ventilator-associated pneumonia rates in
      a hospital of Shanghai: findings of the International Nosocomial Infection
      Control Consortium.
AB  - PURPOSE: The aim of this study was to analyze the impact of a multidimensional
      infection control approach on the reduction of ventilator-associated pneumonia
      (VAP) in intensive care units (ICUs) patients of one hospital in China. MATERIALS
      AND METHODS: We conducted a before-after study from January 2005 to July 2009,
      which was divided into baseline (phase 1) and intervention (phase 2) periods.
      During phase 1, active prospective outcome surveillance of VAP was performed by
      applying the definitions of the Centers for Disease Control and
      Prevention/National Health Safety Network, and the methodology of the
      International Nosocomial Infection Control Consortium. During phase 2, the
      multidimensional approach was implemented. Ventilator-associated pneumonia rates
      obtained in phases 1 and 2 were compared in yearly periods. RESULTS: We recorded
      data from 16,429 patients hospitalized in 3 ICUs, for a total of 74,116 ICU bed
      days. The VAP baseline rate was 24.1 per 1000 ventilator-days. During phase 2,
      the VAP rate significantly decreased to 5.7 per 1000 ventilator-days in 2009
      (2009 vs 2005: relative risk, 0.31; 95% confidence interval, 0.16-0.36; P =
      .0001), amounting to a 79% cumulative VAP rate reduction. CONCLUSIONS:
      Implementing a multidimensional infection control intervention for VAP was
      associated with a significant cumulative reduction in the VAP rate in our ICUs.

PMID- 22386223
TI  - Decreased plasma gelsolin is associated with 1-year outcome in patients with
      traumatic brain injury.
AB  - PURPOSE: Decreased plasma gelsolin level has been associated with 1-month
      mortality after traumatic brain injury (TBI). Thus, we investigated the ability
      of gelsolin to predict 1-year mortality and functional outcome in these patients.
      METHODS: One hundred fourteen healthy controls and 114 patients with acute severe
      TBI were included in this study. Plasma gelsolin concentration on admission was
      measured by ELISA. RESULTS: Fifty-five patients (48.2%) had unfavorable outcome
      (Glasgow Outcome Scale score of 1-3) and 38 patients (33.3%) died in 1 year after
      TBI. Upon admission, plasma gelsolin level in patients was substantially lower
      than that in healthy controls. A multivariate analysis selected plasma gelsolin
      level as an independent predictor for 1-year unfavorable outcome and mortality of
      patients. A receiver operating characteristic curve analysis showed plasma
      gelsolin level predicted 1-year unfavorable outcome and mortality statistically
      significantly. The predictive value of the gelsolin concentration was thus
      similar to that of Glasgow Coma Scale (GCS) score. In a combined logistic
      regression model, gelsolin did not statistically significantly improve the area
      under curve of GCS score. CONCLUSIONS: Plasma gelsolin level is a useful,
      complementary tool to predict functional outcome and mortality 1 year after TBI.

PMID- 22386224
TI  - Usefulness of heart-type fatty acid-binding protein in patients with severe
      sepsis.
AB  - PURPOSE: The purpose of the study was to evaluate the value of heart-type fatty
      acid-binding protein (hFABP) as a novel clinical biomarker in patients with
      severe sepsis. METHODS: Serum concentrations of hFABP and traditional cardiac
      biomarkers including cardiac troponin I, creatine kinase-MB, and B-type
      natriuretic peptides levels were measured within 6 hours after admission in 93
      severe septic patients. The value of hFABP for the diagnosis of sepsis-related
      myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was
      evaluated by receiver operating characteristics curve analysis. The prognostic
      value of elevated hFABP was subsequently confirmed by multivariate Cox
      proportional hazards analysis and Kaplan-Meier survival analysis. RESULTS: Heart
      type fatty acid-binding protein was elevated (>= 4.5 ng/mL) in 58 (62.4%)
      patients; patients with elevated hFABP appeared more likely to have SRMD (84.5%
      vs 31.4%, P < .001) and have higher prevalence of 28-day death (37.9% vs 8.6%, P
      = .002). Heart-type fatty acid-binding protein offered superior value over
      conventional biomarkers in both diagnosis of SRMD (area under the curve, 0.767; P
      < .001) and prediction of 28-day death (area under the curve, 0.805; P < .001).
      CONCLUSIONS: Serum hFABP is frequently elevated among patients with severe sepsis
      and appears to be associated with SRMD. Elevated hFABP independently predicts 28
      day mortality in severe sepsis.

PMID- 22386225
TI  - Portable miniaturized extracorporeal membrane oxygenation systems for H1N1
      related severe acute respiratory distress syndrome: a case series.
AB  - BACKGROUND: Technological advances improved the practice of "modern"
      extracorporeal membrane oxygenation (ECMO). In the present report, we describe
      the experience of a referral ECMO center using portable miniaturized ECMO systems
      for H1N1-related severe acute respiratory distress syndrome (ARDS). METHODS: An
      observational study of all patients with H1N1-associated ARDS treated with ECMO
      in Hospital S. Joao (Porto, Portugal) between November 2009 and April 2011 was
      performed. Extracorporeal membrane oxygenation support was established using
      either ELS or Cardiohelp systems (Maquet-Cardiopulmonary-AG, Hirrlingen,
      Germany). RESULTS: Ten adult patients with severe ARDS secondary to H1N1
      infection (Pao(2)/fraction of inspired oxygen, 69 mm Hg [56-84]; Murray score,
      3.5 [3.5-3.8]) were included, and 60% survived to hospital discharge. Five
      patients were uneventfully transferred on ECMO from referring hospitals to our
      center by ambulance. Six patients were treated during the first postpandemic
      influenza season. All patients were treated with oseltamivir, and 1 received in
      addition zanamivir. Four patients received corticosteroids. Nosocomial infection
      was the most common complication (40%). Of the 4 deaths, 2 were caused by
      hemorrhagic shock; 1, by irreversible multiple organ failure; and 1, by
      refractory septic shock. CONCLUSION: In our experience, ECMO support was a
      valuable therapeutic option for H1N1-related severe ARDS. The use of portable
      miniaturized systems allowed urgent rescue of patients from referring hospitals
      and safe interhospital and intrahospital transport during ECMO support.

PMID- 22386226
TI  - A new parameter for the diagnosis of hemorrhagic shock: jugular index.
AB  - PURPOSE: The purpose of this study is to investigate whether there are any
      significant changes in the diameter and the area of the internal jugular vein
      (IJV) during the hemorrhagic shock. MATERIALS AND METHODS: Healthy volunteers
      donating blood were included in the study. Arterial blood pressure, pulse rate,
      anteroposterior (AP) and transverse diameter, and area measurements of the IJV
      during inspiration and expiration were performed on the volunteers before and
      after 450 mL of blood donation. RESULTS: A total of 35 volunteers were enrolled
      in the study. The IJV prehemorrhagic AP diameters during inspiration and
      expiration were 4.9 +/- 2.2 and 7.9 +/- 3.1 mm, and the posthemorrhagic values
      were 2.7 +/- 1.6 and 6.6 +/- 3.1 mm (respectively, P < .001 and P = .007). The
      jugular index-AP was 36% +/- 15% before hemorrhage and 58% +/- 17% after
      hemorrhage (P < .001). The IJV areas during inspiration and expiration were 0.40
      +/- 0.28 and 0.81 +/- 0.51 cm(2) before hemorrhage and were 0.14 +/- 0.15 and
      0.61 +/- 0.47 cm(2) after hemorrhage (for both, P < .001). The jugular index-area
      was found as 47% +/- 18% before hemorrhage and as 73% +/- 18% after hemorrhage (P
      < .001). CONCLUSIONS: We believe that measurement of the IJV and the jugular
      index is a reliable indicator of class 1 hemorrhagic shock. It may be used as a
      part of focused abdominal sonography for trauma in clinical practice.

PMID- 22386227
TI  - Usefulness of cardiac biomarkers to predict cardiac recovery in patients on
      extracorporeal membrane oxygenation support for refractory cardiogenic shock.
AB  - BACKGROUND: No prognostic markers of myocardial recovery in patients with
      refractory cardiogenic shock requiring circulatory support are known, but early
      identification of patients who will not recover might provide an opportunity to
      change the treatment strategy to improve outcome. Because N-terminal fragment of
      the B-type natriuretic peptide, troponin Ic, midregional fragment of the
      proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic
      markers in patients with cardiac failure, we hypothesized that, among patients
      with refractory cardiogenic shock of potentially reversible cause supported with
      extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might
      help identify patients who would recover. METHODS: This was a prospective,
      observational, single-center study in a medical-surgical intensive care unit.
      Among 41 consecutive patients with refractory cardiogenic shock of potentially
      reversible cause receiving ECMO support, 18 recovered and were successfully
      weaned off the machine. Blood N-terminal fragment of the B-type natriuretic
      peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide,
      proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and
      7 post-ECMO. RESULTS: Neither the absolute values of those biomarkers at days 1,
      3, or 7 nor their kinetics during the first week differed between patients weaned
      or not. Areas under the receiver operating characteristic curves (95% confidence
      interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery
      were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and
      0.61 (0.43-0.78), respectively. CONCLUSION: In patients with refractory
      cardiogenic shock of potentially reversible cause receiving ECMO support, early
      measurements of cardiac biomarkers are not useful for identifying those who would
      recover.

PMID- 22386228
TI  - The role of pharmacists and emergency contraception: Are pharmacists' perceptions
      of emergency contraception predictive of their dispensing practices?
AB  - BACKGROUND: Pharmacists can play a critical role in the access to emergency
      contraception (EC). We assessed if knowledge and attitudes were predictive of EC
      dispensing among a statewide sample of Florida pharmacists, who have legal
      authority to refuse to dispense medications. STUDY DESIGN: In 2008, surveys were
      mailed to a random sample of 1264 pharmacists registered with the Florida Board
      of Pharmacy. Data from 272 pharmacists (22% response rate) were analyzed using
      bivariate and multivariate logistic regression. RESULTS: Fifty-six percent of
      respondents incorrectly answered that EC causes birth defects, and 46% replied
      that it causes abortion. Only 22% said that EC can be purchased in advance of
      need. Many felt uncomfortable dispensing to adolescents (61%) and men (58%).
      Knowledge about EC was the most important predictor of dispensing [odds ratio
      (OR)=1.57, 95% confidence interval (CI) 1.22-2.03]. In particular, pharmacists
      who reported that EC does not act as an abortifacient were more likely to
      dispense it (OR=4.64, 95% CI 2.15-10.00). CONCLUSIONS: Correct information about
      EC was the most important predictor of pharmacists' dispensing EC. To expand
      availability of EC, pharmacists will have to become better informed.

PMID- 22386229
TI  - Prostate-specific antigen as a biomarker of condom failure: comparison of three
      laboratory assays and self-reported condom use problems in a randomized trial of
      female condom performance.
AB  - BACKGROUND: Prostate-specific antigen (PSA), a biomarker for semen exposure, may
      provide a more objective measure of condom failure than subject self-reports.
      Methods for measuring PSA vary and their comparability with respect to assessing
      condom performance has not been adequately evaluated. This study compared results
      from three different PSA assays of vaginal samples collected by subjects in a
      randomized clinical trial which compared the performance of female condoms. STUDY
      DESIGN: We selected 30 pairs of pre- and post-coital vaginal samples from
      subjects who reported condom functionality problems or whose original PSA assay
      was positive. Samples were retested using three different PSA assays
      [quantitative enzyme-linked immunoassay (EIA), rocket immune-electrophoresis
      (RIE) and chromatographic immunoassay (CIA)]. We compared the proportion of
      condom uses where the post-coital PSA result indicated semen exposure for each of
      the three assays. RESULTS: Despite varying levels of sensitivity, the results
      from all three assays were remarkably consistent. Self-reported condom failures
      did not correlate well with positive PSA results, suggesting that exclusive
      reliance on either PSA or user self-report may be inadequate for assessing condom
      functionality. CONCLUSION: In combination with user self-report of condom
      failure, PSA testing provides a reliable, objective marker of condom
      functionality. Studies based on PSA testing may improve on conventional
      contraceptive clinical trials by offering a more direct assessment of a condom
      product's ability to prevent semen exposure.

PMID- 22386230
TI  - Emergency contraception: global challenges, new opportunities.

PMID- 22386231
TI  - Conducting high-quality research on the psychological impact of oral
      contraceptive use.

PMID- 22386232
TI  - Characterization of the bacterial archaeal diversity in hydrocarbon-contaminated
      soil.
AB  - A polyphasic approach combining culture-based methods with molecular methods is
      useful to expand knowledge on microbial diversity in contaminated soil. Microbial
      diversity was examined in soil samples from a former industrial site in the
      European Alps (mainly used for aluminum production and heavily contaminated with
      petroleum hydrocarbons) by culture-dependent and culture-independent methods. The
      physiologically active eubacterial community, as revealed by fluorescence-in-situ
      hybridization (FISH), accounted for 6.7% of the total (DAPI-stained) bacterial
      community. 4.4% and 2.0% of the DAPI-stained cells could be attributed to
      culturable, heterotrophic bacteria able to grow at 20 degrees C and 10 degrees C,
      respectively. The majority of culturable bacterial isolates (34/48) belonged to
      the Proteobacteria (with a predominance of Alphaproteobacteria and
      Gammaproteobacteria), while the remaining isolates were affiliated with the
      Actinobacteria, Cytophaga-Flavobacterium-Bacteroides and Firmicutes. A high
      fraction of the culturable, heterotrophic bacterial population was able to
      utilize hydrocarbons. Actinobacteria were the most versatile and efficient
      degraders of diesel oil, n-alkanes, phenol and PAHs. The bacterial 16S rRNA gene
      clone library contained 390 clones that grouped into 68 phylotypes related to the
      Proteobacteria, Bacteroidetes, Actinobacteria and Spirochaetes. The archaeal 16S
      rRNA gene library contained 202 clones and 15 phylotypes belonging to the phylum
      Euryarchaeota; sequences were closely related to those of methanogenic archaea of
      the orders Methanomicrobiales, Methanosarcinales, Methanobacteriales and
      Thermoplasmatales. A number of bacterial and archaeal phylotypes in the clone
      libraries shared high similarities with strains previously described to be
      involved in hydrocarbon biodegradation. Knowledge of the bacterial and archaeal
      diversity in the studied soil is important in order to get a better insight into
      the microbial structure of contaminated environments and to better exploit the
      bioremediation potential by identifying potential hydrocarbon degraders and
      consequently developing appropriate bioremediation strategies.

PMID- 22386233
TI  - Short and long term changes in carbon, nitrogen and acidity in the forest soils
      under oak at the Alice Holt Environmental Change Network site.
AB  - The dynamics of soil properties within a 70 year old oak plot were assessed every
      five years (1994-2009), by depth and by horizon to identify short term changes in
      soil carbon and nitrogen stocks, and acidity. The findings were set within a
      study of long term changes in soil properties in a 180 year chronosequence of oak
      plots from the same forest. Carbon stock increased significantly in the top
      mineral horizon - overall increase was 5 t C ha(-1), at a mean accumulation rate
      of 0.34 t C ha(-1)y(-1), which was mainly due to increase in horizon thickness.
      No increase was seen when soils were sampled by depth. Differences obtained by
      depth or horizon sampling due to changes in horizon thickness over time highlight
      the importance of horizon in the correct evaluation of soil property change in
      small scale sampling programs. This is particularly important in forest soils
      with high litter accumulation and low turnover rates when compared to other land
      uses. Nitrogen stock increases below 10cm soil depth were attributed to insect
      activity, litterfall variation and a change in water table. Findings were
      confirmed in the chronosequence study of oak across the forests; increases in
      soil C stocks of 0.1-0.2 t C ha(-1)y(-1) were calculated across young (~25
      years), mid-rotation (~60 years) and old (120+ years) stands. Soil nitrogen
      increased significantly with canopy age whilst pH increased significantly between
      young-mid rotation stands but decreased between mid rotation and old stands.
      Significant increases in pH were also recorded before 2004 in the ECN 70 year old
      oak plots reflecting overall pollution recovery.

PMID- 22386234
TI  - Biomagnification of organohalogens in Atlantic salmon (Salmo salar) from its main
      prey species in three areas of the Baltic Sea.
AB  - Factors affecting the biomagnification of organohalogens in Baltic salmon from
      sprat, herring and three-spined stickleback were assessed in three feeding areas.
      Second sea-year salmon contained (in fresh weight of whole fish) 79-250ngg(-1)
      polychlorinated biphenyls (SigmaPCB), 0.9-2.7pgg(-1) dibenzo-p-dioxins
      (SigmaPCDD), 8-19pgg(-1) dibenzofurans (SigmaPCDF), 96-246pgg(-1) coplanar PCBs,
      2.4-3.6ngg(-1) polybrominated diphenylethers (SigmaPBDE), and 39-136ngg(-1)
      Sigma(indicator) PCB6. The EU limits for WHO toxic equivalent concentrations in
      fish feed were already exceeded in one-year-old sprat and herring and were
      exceeded many-fold in older age groups. The differences in the biomagnification
      rates of organohalogens in salmon appeared to be related to the feeding area,
      principal prey species, and the fat content and growth rate of the prey species.

PMID- 22386235
TI  - Relationships between body burdens of trace metals (As, Cu, Fe, Hg, Mn, Se, and
      Zn) and the relative body size of small tooth flounder (Pseudorhombus jenynsii).
AB  - Several studies have described strong relationships between body size and the
      accumulation of trace metals in animal tissues. However, few of these studies
      have utilized aging techniques to control for age related effects. We utilized
      relative body size (gy(-1)) of a model flounder species, Pseudorhombus jenynsii,
      in order to control for age related effects on growth and size measurements. We
      investigated links between relative body size, concentrations of trace metals in
      flounder muscle tissue, physico-chemical variables (temperature, salinity, pH,
      and turbidity), and levels of trace metals in the sediment. Flounder were sampled
      using an otter trawl net in the inner areas of eight estuaries that were either
      heavily modified or relatively unmodified by urbanization and industrial
      activity. Our results indicate that this commonly eaten fish is accumulating
      significant levels of some trace metals in their muscle tissue, both in
      relatively unmodified and heavily modified estuaries. Concentrations of Cu, Zn
      and Fe in muscle tissue, as well as temperature, showed a negative relationship
      to the relative body size of flounder. In contrast, Se and Hg in muscle showed a
      positive relationship to relative body size. Observed growth patterns indicate
      that these effects are not driven by age related differences in metabolic
      activity. Instead, our results suggest that differences in food supply or
      toxicological effects may be responsible for the observed relationships between
      relative body size and concentrations of Cu, Zn, and Se in muscle tissues. The
      use of otolith aging and growth measurement techniques represents a novel method
      for assessing the relationships between trace metal accumulation and the relative
      body size of fish in a field environment.

PMID- 22386236
TI  - Evaluation of the national nursing model and four nursing documentation systems
      in Finland--lessons learned and directions for the future.
AB  - OBJECTIVES: To evaluate the feasibility of the national nursing model and
      usability of four widely used nursing documentation systems and to study their
      usefulness in multi-professional collaboration and information exchange. METHODS:
      Qualitative usability study methods were used, including the use of scenario
      walkthroughs, contextual inquiries, thematic interviews and inspection-based
      expert reviews in the users' clinical contexts. RESULTS: The nursing process
      model was shown to be feasible in nursing practice but the national nursing
      classification was considered too detailed, multi-layered and difficult to use
      and understand. The four evaluated nursing documentation systems had many
      usability problems which resulted in them being difficult to use and produced
      extra documentation workload. Generally, electronic nursing documentation
      improves patients' and health professionals' legal protection and makes nursing
      care more transparent; however, the documentation systems did not provide good
      support for multi-professional care and information exchange. CONCLUSIONS:
      Nursing models should comply better with nursing practices and support nurses in
      patient care and interventions. An essential improvement in practice would be the
      use of specific templates that are easy to apply in specific situations with
      homogeneous patient groups. Collaborative care aspects and better utilization of
      information require that the nursing model is designed to support not just
      documentation but also information utilization.

PMID- 22386237
TI  - Compatibility of current DSM-IV and proposed DSM-5 diagnostic criteria for
      cocaine use disorders.
AB  - OBJECTIVES: The present study examined the compatibility of the current DSM-IV
      and proposed DSM-5 diagnostic criteria for cocaine use disorders (CUD) among
      state prison inmates, and evaluated the diagnostic utility of the proposed
      criteria in accounting for DSM-IV "diagnostic orphans" (i.e., individuals who
      meet one or two of the diagnostic criteria for substance dependence yet fail to
      report indications of substance abuse). METHOD: Data were derived from routine
      clinical assessments of adult male inmates (N=6871) recently admitted to the
      Minnesota Department of Corrections state prison system from 2000 to 2003. An
      automated (i.e., computer-prompted) version of the Substance Use Disorder
      Diagnostic Schedule-IV (SUDDS-IV; Hoffmann & Harrison, 1995) was administered to
      all inmates as part of routine assessments. DSM-IV and DSM-5 criteria were coded
      using proposed guidelines. RESULTS: The past 12-month prevalence of DSM-IV CUDs
      was 12.7% (Abuse, 3.8%, Dependence, 8.9%), while 11.0% met past 12-month DSM-5
      criteria for a CUD (Moderate [MCUD], 1.7%; Severe [SCUD], 9.3%). When DSM-5
      criteria were applied, 11.8% of the DSM-IV diagnostic orphans received a MCUD
      diagnosis. The vast majority of those with no diagnosis (99.6%) continued to have
      no diagnosis, and a similar proportion who met dependence criteria (98.4%) met
      SCUD criteria of the proposed DSM-5. Most of the variation in diagnostic
      classifications was accounted for by those with a current abuse diagnosis.
      CONCLUSIONS: The proposed DSM-5 criteria perform similarly to DSM-IV criteria in
      terms of the observed past 12-month CUD prevalence and diagnostic
      classifications. The proposed criteria appear to account for diagnostic orphans
      that may warrant a diagnosis. DSM-IV abuse cases were most affected when DSM-5
      criteria were applied. Additional criteria, beyond those included in the proposed
      DSM-5 changes, concerning use to relieve emotional stress and preoccupation with
      use were frequently endorsed by those with a proposed DSM-5 diagnosis.

PMID- 22386238
TI  - [Drug's administration via feeding tubes: evaluation of practices in an intensive
      care unit of a Tunisian hospital].
AB  - INTRODUCTION: Drugs' administration via feeding tubes is a potential source of
      iatrogenic events for the intensive care patients because of the problem of not
      adapted galenic forms. OBJECTIVES: We analyzed the prescriptions of patients with
      enteral feedings to determine if the galenic forms were compatible with
      administration via feeding tubes. We also observed and analyzed the methods of
      drugs passage by nurses. PATIENTS AND METHODS: We analyzed 30 prescriptions of
      patients with enteral feedings in the intensive care unit of Habib Bourguiba Sfax
      hospital, by a prospective and exhaustive way. We also, observed and evaluated
      the practices of preparation and administration of drugs to these patients via
      feeding tube by nurses. RESULTS: Only 12% of drugs were liquids. Eighty-eight
      percent of the drugs were pulverised and capsule open before administration. The
      galenic form was not in conformity for 20% of drugs because of the prohibition to
      crushing tablet or opening capsule (gastroresistant form was dissolved), or
      because of the administration of a parenteral form (risk of irritation). Among 78
      drugs administered by 10 different nurses, the time between passage of the drug
      and enteral nutrition were not respected for 59% of the observations. The drugs
      were managed in mixture for 90% of the observations. The gloves were not worn in
      80% of observations. No rinsing is made between consecutive administrations and
      before administration. CONCLUSION: This study shows that it is possible to reduce
      risk of administration errors in the intensive care unit and to facilitate the
      administration of drug via feeding tube by prescribing liquid oral form or
      soluble solid oral form. It also shows the need for cooperation with the
      pharmacist in order to adapt the galenic forms and to redact protocol of
      administration.

PMID- 22386239
TI  - Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant
      prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.
AB  - Ixabepilone is an epothilone B analogue with activity in a variety of solid
      malignancies, including prostate cancer. The main dose-limiting toxicity of
      ixabepilone is myelosuppression when administered by using an every 3-week
      schedule. Here we evaluate the activity of a weekly ixabepilone in men with
      metastatic castrate-resistant prostate cancer to minimize hematologic toxicity.
      PURPOSE: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in
      taxane-resistant cancer cell lines. Here we report the activity and toxicity of
      ixabepilone, administered by using a weekly schedule, in men with metastatic
      castrate-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: Patients with
      metastatic CRPC received ixabepilone at 20 mg/m(2) intravenous weekly x 3, in 4
      week cycles. This noncomparative study stratified patients to either a
      chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx)
      chemotherapy arm. The primary endpoint was prostate-specific antigen response by
      using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints
      included radiographic response when using RECIST (Response Evaluation Criteria In
      Solid Tumors). RESULTS: In total, 124 patients were enrolled, of whom, 109 were
      eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in
      this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12
      (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response
      in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax,
      and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6
      (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8
      (20.5%), 12 (25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4
      thrombocytopenia was infrequent and seen in only one patient on the CN and the
      TCx arm. CONCLUSION: Ixabepilone was found to have an acceptable toxicity profile
      when administered by using a weekly schedule with less myelosuppression compared
      with prior studies when using the every 3-week schedule. Single-agent activity
      was observed and met prespecified activity levels for the Tax treated arm.

PMID- 22386240
TI  - Expression of microRNAs in the urine of patients with bladder cancer.
AB  - We quantified the urine sediment and supernatant levels of microRNA (miRNA)
      targets related to epithelial-mesenchymal transition in 51 patients with bladder
      cancer and in 24 controls. We found that patients with bladder cancer had
      depressed levels of the miR-200 family, miR-192, and miR-155 in urinary sediment.
      The urinary level of these miRNAs may be developed as noninvasive markers for
      bladder cancer. BACKGROUND: MicroRNAs (miRNA) have been implicated to play an
      important role in the pathogenesis of a variety of cancers. We studied the levels
      of miRNAs related to epithelial-mesenchymal transition (EMT) in the urine of
      patients with bladder cancer. METHOD: The expression of the miR-200 family, miR
      205, miR-192, miR-155, and miR-146a in the urine sediment and supernatant of 51
      patients with bladder cancer and in 24 controls was determined by real-time
      quantitative polymerase chain reaction. RESULTS: Compared with controls, the
      patients with bladder cancer had a lower expression of the miR-200 family, miR
      192, and miR-155 in the urinary sediment; lower expression of miR-192; and higher
      expression of miR-155 in the urinary supernatant. The expression of the miR-200
      family, miR-205, and miR-192 in the urine sediment significantly correlated with
      urinary expression of EMT markers, including zinc finger E-box-binding homeobox
      1, vimentin, transforming growth factor beta1, and Ras homolog gene family,
      member A. Furthermore, the levels of miR-200c and miR-141 in the urine sediment
      became normalized after surgery. CONCLUSION: We found that the urinary miR-200
      family, miR-155, miR-192, and miR-205 levels are depressed in patients with
      bladder cancer. The level of these miRNA targets in urine has the potential to be
      developed as noninvasive markers for bladder cancer.

PMID- 22386241
TI  - Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl
      piperazine-1-yl)-propyl ester derivatives as new analgesic agents.
AB  - A series of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester
      derivatives were synthesized through discovery strategies for balancing target
      based in vitro screening and phenotypic in vivo screening. All the newly
      synthesized compounds were screened for their analgesic activities and compared
      with standard drug morphine. Among them, compound 44r, a potent analgesic agent
      that has favorable pharmacokinetic properties in rats and most importantly, has a
      wide safety margin. We demonstrated with in vitro and in vivo functional assays
      that its analgesic activity might be through 5-HT(2A) antagonism to some extent.
      Hence, it is concluded that there is ample scope for further study in developing
      compound 44r as a good lead candidate for an analgesic agent.

PMID- 22386242
TI  - N-Caffeoyl serotonin as selective COX-2 inhibitor.
AB  - The inhibitory effects of the synthetic serotonin analogues (1-8) on COX (1 and
      2) were evaluated. Two serotonin derivatives (4 and 8) showed inhibitory effect
      of COX (1 and 2). Especially, 4 exhibited excellent inhibitions on COX-2 with
      extremely high potency (IC(50)=42.5 MUM). The inhibitory activities of cinnamic
      acid derivatives and serotonin were evaluated to clarify whether inhibitory
      activities of compound 4 and 8 are due to cinnamic acid moiety or serotonin
      moiety. Caffeic acid and N-caffeoyl serotonin (4) exhibited selective inhibition
      of COX-2 compared to aspirin. Comparison caffeic acid with 4 suggested that the
      linkage of caffeic acid and serotonin enhance COX-2 inhibition. Comparison of
      structures of caffeic acid and sinapic acid implied that catechol moiety of
      cinnamic acid derivatives is a major contributing factor for selective inhibition
      of COX-2. The selective COX-2 inhibitory activity of compound 4 is significant
      and could be employed as drugs against inflammatory and allergy.

PMID- 22386243
TI  - Discovery of thiadiazole amides as potent, S1P3-sparing agonists of sphingosine-1
      phosphate 1 (S1P1) receptor.
AB  - High-throughput screening of GSK compound collection led to the discovery of a
      novel series of thiadiazole amides as potent and S1P(3)-sparing sphingosine-1
      phosphate 1 (S1P(1)) receptor agonists. Synthesis, structure and activity
      relationship, selectivity, and some developability properties are described.

PMID- 22386244
TI  - Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified
      through virtual screening.
AB  - A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2
      hydroxybenzamide scaffold linker was discovered through virtual screening. The X
      ray structure of hK6 complexed with compound 9b was determined to a resolution of
      1.68A. The tertiary folding of the hK6 complexed with the inhibitor is conserved
      relative to the structure of the apo-protein, whereas the interaction between hK6
      and the inhibitor is consistent with both the SAR and the in silico model used in
      the virtual screening.

PMID- 22386245
TI  - Faculty and administrators: adversaries or collaborative partners?

PMID- 22386246
TI  - Response to integrating simulation into a foundational gerontological nursing
      course.

PMID- 22386248
TI  - Gut feelings about diabetes.
AB  - Studies of patients going into diabetes remission after gastric bypass surgery
      have demonstrated the important role of the gut in glucose control. The
      improvement of type 2 diabetes after gastric bypass surgery occurs via weight
      dependent and weight independent mechanisms. The rapid improvement of glucose
      levels within days after the surgery, in relation to change of meal pattern,
      rapid nutrient transit, enhanced incretin release and improved incretin effect on
      insulin secretion, suggest mechanisms independent of weight loss. Alternatively,
      insulin sensitivity improves over time as a function of weight loss. The role of
      bile acids and microbiome in the metabolic improvement after bariatric surgery
      remains to be determined. While most patients after bariatric surgery experienced
      sustained weight loss and improved metabolism, small scale studies have shown
      weight regain and diabetes relapse, the mechanisms of which remain unknown.

PMID- 22386249
TI  - Effect of excessive methionine on the development of the cranial growth plate in
      newborn rats.
AB  - OBJECTIVE: Methionine is an essential amino acid and pivotal for normal growth
      and development. However, previous animal studies have shown that excessive
      maternal intake of methionine causes growth restrictions, organ damages, and
      abnormal growth of the mandible in newborn animals. However, the effect of
      excessive methionine on the development of the cranial growth plate is unknown.
      This study investigated histological alterations of the cranial growth plate
      induced by high methionine administration in newborn rats. DESIGN: Twenty
      pregnant dams were divided into a control and an experimental group. The controls
      received a diet for rats and the experimental group was fed from the 18th
      gestational day with a special manufactured high methionine diet for rats. The
      high methionine diet was maintained until the end of the lactation phase (day
      20). The offspring of both groups were killed at day 10 or 20 postnatally and
      their spheno-occipital synchondroses were collected for histological analysis.
      RESULTS: The weight of the high-dose methionine treated experimental group was
      considerably reduced in comparison to the control group at day 10 and 20
      postnatally. The cartilaginous area of the growth plate and the height of the
      proliferative zone were markedly reduced at postnatal day 10 in the experimental
      group. CONCLUSIONS: In summary, the diet-induced hypermethioninemia in rat dams
      resulted in growth retardations and histomorphological changes of the spheno
      occipital synchondrosis, an important craniofacial growth centre in newborns.
      This finding may elucidate facial dysmorphoses reported in patients suffering
      from hypermethioninemia.

PMID- 22386250
TI  - Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE(
      /-) mice from the development of atherosclerosis.
AB  - AIM: MIC-1/GDF15 is a member of the TGF-b superfamily, which is thought to have
      pleiotropic roles in stress responses, inflammation, tissue injury and repair,
      energy homeostasis, and malignancy. MIC-1/GDF15 was recently identified as a new
      biomarker for the development of cardiovascular events and the outcome of
      atherosclerotic disease therapy. The aim of our study was to determine if MIC-1
      also directly exerts pro- or antiatherogenic properties during the development of
      atherosclerosis. METHODS AND RESULTS: We investigated the effect of transgenic
      overexpression of MIC-1 in macrophages in the ApoE(-/-) mouse model of
      atherosclerosis. After 6 months of high-fat diet, MIC-1/GDF15 transgenic ApoE(-/
      ) mice had smaller atherosclerotic lesions; however, no differences in lesion
      composition, pro- or anti-inflammatory cytokine production, or serum levels of
      lipids or cytokines were detected. CONCLUSIONS: Our results suggest that MIC-1
      has an overall protective effect on the disease process, but further studies will
      be required to define its mechanism of action.

PMID- 22386251
TI  - Diagnostic value of anteroposterior diameter of fetal renal pelvis during second
      and third trimesters in predicting postnatal surgery among Korean population:
      useful information for antenatal counseling.
AB  - OBJECTIVE: To establish prognostic data regarding fetal hydronephrosis using the
      anteroposterior diameter (APD) and the need for interventional surgery in the
      Korean population. METHODS: A total of 187 children with an APD of >= 4 mm on
      obstetric ultrasound scans at any gestational age were retrospectively reviewed.
      The affected renal units were divided into 2 groups: surgical and nonsurgical.
      The ultrasound findings were compared at 3 gestational ages: second trimester (15
      26 weeks' gestation), early third trimester (27-33 weeks' gestation), and late
      third trimester (34-40 weeks' gestation). RESULTS: The area under the receiver
      operating characteristic curve was 0.770, 0.828, and 0.812 at the second, early
      third, and late third trimesters, respectively. A 100% sensitivity for predicting
      postnatal surgery could be achieved at a cutoff APD of 5 mm during the second
      trimester, 8 mm during the early third trimester, and 10 mm during the late third
      trimester if scheduled antenatal ultrasound scans were performed. A cutoff APD of
      11 mm during the second trimester was of diagnostic value in selecting children
      at risk of postnatal surgery with an odds ratio of 5.13 (95% confidence interval
      1.62-16.25), with relatively high sensitivity and specificity. With a cutoff of
      15 mm during the early third and late third trimesters, the odds ratio was 11.51
      (95% confidence interval 5.05-26.23) and 6.94 (95% confidence interval 3.30
      14.57), respectively. CONCLUSION: Compared with an APD of 10 mm, the most
      commonly used standard cutoff value in predicting postnatal hydronephrosis and
      its outcome, an APD cutoff of 5, 8, and 10 mm during the second, early third, and
      late third trimesters, respectively, is more specific in predicting the need for
      postnatal surgical intervention in the Korean population.

PMID- 22386253
TI  - Bilateral renal cell carcinoma in a child.
AB  - Renal cell carcinoma is a rare renal tumor in the pediatric population with an
      incidence of 0.1-0.3%. We report on the first case of bilateral renal clear cell
      carcinoma that was treated by partial nephrectomies. We performed a complete
      genetic evaluation to exclude a family inheritance and we looked at the deletions
      associated with the possible histologic subtypes of renal cell carcinoma. The
      patient had no evidence of recurrence after 80-month follow-up and her renal
      function remained normal.

PMID- 22386252
TI  - Clinical and pathologic factors of prognostic significance in penile squamous
      cell carcinoma in a North American population.
AB  - OBJECTIVE: To analyze, in a clinicopathologic correlation study, a small
      population of primarily white men with invasive squamous cell carcinoma of the
      penis for potential prognostic predictors. Penile squamous cell carcinoma is an
      uncommon cancer in North America. It has a wide spectrum of clinical behavior and
      an understudied pathogenesis. METHODS: The data from 43 patients with invasive
      squamous cell carcinoma of the penis were studied retrospectively. Extensive
      chart reviews were conducted, glass slides were reviewed, and tissue microarrays
      were constructed for analysis of immunohistochemical stains p16(INK4a), p53, and
      Ki-67. Univariate and multivariate logistic regression analyses were performed to
      elucidate any clinical or pathologic factors that would predict overall survival.
      RESULTS: The mean age at diagnosis was 63 years. Most cases (63%) were invasive
      squamous cell carcinoma, not otherwise specified, and presented as pathologic
      stage T1 or T2 tumors. Of the 43 patients, 23% died of their disease; 53% of the
      cases stained for p16(INK4a). Higher pathologic tumor stage and a lack of
      p16(INK4a) staining were independent predictors of worse overall survival (P =
      .014) and cancer-specific survival (P = .010). CONCLUSION: Our results have shown
      that 53% of the invasive penile squamous cell carcinoma cases in this population
      were associated with human papillomavirus, using p16(INK4a) as a surrogate marker
      of human papillomavirus infection. These patients had a statistically significant
      survival advantage, independent of other prognostic factors.

PMID- 22386254
TI  - Determination of nitrophenols using ultrahigh pressure liquid chromatography and
      a new manual shaking-enhanced, ultrasound-assisted emulsification microextraction
      method based on solidification of a floating organic droplet.
AB  - Nitrophenols are toxic compounds in the wastewater. In the proposed method, a new
      technique using a manual shaking-enhanced, ultrasound-assisted emulsification
      microextraction (MS-USAEME) method based on solidification of a floating organic
      droplet combined with ultrahigh pressure liquid chromatography (UHPLC) has been
      developed for the extraction and determination of nitrophenols in aqueous
      samples. In this method, the low toxicity extraction solvent 1-undecanol was used
      to extract the nitrophenols. After centrifugation, ice bath was used to solidify
      the floating extraction solvent, using microtubes to collect the floated
      extraction solvent and diluting with 30 MUL of dimethyl sulfoxide, then injecting
      into the UHPLC for further analysis. The relative standard deviations (RSD) were
      6-12%, enrichment factors (EFs) were 62-500, the relative recoveries (RR) of this
      method were 80-110% for spiked lake water samples. The detection limits of this
      method were 0.5-3.0 MUg L-1 for spiked lake water and 0.6-3.2 MUg L-1 for spiked
      agriculture water. The further performance of the proposed method was gauged by
      analyzing field samples.

PMID- 22386255
TI  - Simultaneous determination of polycyclic aromatic hydrocarbons and benzene,
      toluene, ethylbenzene and xylene in water samples using a new sampling strategy
      combining different extraction modes and temperatures in a single extraction
      solid-phase microextraction-gas chromatography-mass spectrometry procedure.
AB  - This study proposes a new optimization approach for the simultaneous
      determination of polycyclic aromatic hydrocarbons (PAHs) and benzene, toluene,
      ethylbenzene and xylene isomers (BTEX) from water samples using the solid-phase
      microextraction technique followed by gas chromatography-mass spectrometry (GC
      MS) separation and detection. The objective of the study was to achieve
      compromise extraction conditions, suitable for all semi-volatile and volatile
      compounds, under which the amount extracted is maximized for all analytes. This
      was achieved by careful optimization of the fiber coating, salting-out effect,
      extraction time and temperature and extraction mode (headspace or direct
      immersion). With the optimized fiber coating - PDMS/DVB 65 MUm - the other
      selected factors were optimized using a response surface methodology through
      central composite designs. As expected, the optimized results for each class of
      analytes varied significantly, probably due to the differences in their
      volatility and the equilibrium constants for the analyte/fiber coating. In order
      to overcome this issue, a new optimization approach was proposed based on a
      combination of extraction modes and extraction temperatures in a single
      extraction procedure. The final optimized procedure was: 48 min of extraction in
      direct immersion mode with the sample maintained at 80  degrees C followed by a
      further 32 min of headspace extraction with the sample temperature kept at 10 
      degrees C. The proposed procedure was compared with conventional methods based on
      the use of a single extraction mode and temperature (80 min of headspace
      extraction at 60  degrees C or 80 min of direct immersion extraction at 50 
      degrees C). The newly proposed method was shown to be more attractive as it
      extracted higher amounts of both semi-volatile and volatile compounds in a single
      extraction procedure compared to the conventional approaches. The optimized
      method was validated and excellent results were obtained.

PMID- 22386256
TI  - Hyphenated liquid chromatography-gas chromatography technique: recent evolution
      and applications.
AB  - Liquid chromatography (LC) hyphenated with gas chromatography (GC) was first
      presented in 1979. Since then an intensive study has been carried out to explore
      different types of interfaces both for coupling normal-phase (NP) and reverse
      phase (RP) LC with GC. The present review focuses on the technical progress and
      applications presented in the last decade, and it describes the most used
      interfaces. In fact, more flexible interfaces have been studied to improve the
      use of LC-GC, in particular the use of a programmed temperature vaporizer (PTV)
      injector. An intensive effort has also been devoted to optimizing the coupling of
      reverse-phase LC for analysis of water-based samples. A brief overview of
      comprehensive approaches (LC*GC) is discussed along with perspective for further
      improvement of the technique.

PMID- 22386257
TI  - Prediction of retention times in comprehensive two-dimensional gas chromatography
      using thermodynamic models.
AB  - A method was developed to accurately predict both the primary and secondary
      retention times for a series of alkanes, ketones and alcohols in a flow-modulated
      GC*GC system. This was accomplished through the use of a three-parameter
      thermodynamic model where DeltaH, DeltaS, and DeltaC(p) for an analyte's
      interaction with the stationary phases in both dimensions are known. Coupling
      this thermodynamic model with a time summation calculation it was possible to
      accurately predict both (1)t(r) and (2)t(r) for all analytes. The model was able
      to predict retention times regardless of the temperature ramp used, with an
      average error of only 0.64% for (1)t(r) and an average error of only 2.22% for
      (2)t(r). The model shows promise for the accurate prediction of retention times
      in GC*GC for a wide range of compounds and is able to utilize data collected from
      1D experiments.

PMID- 22386258
TI  - Supercritical fluid chromatographic resolution of water soluble isomeric
      carboxyl/amine terminated peptides facilitated via mobile phase water and ion
      pair formation.
AB  - Both analytical scale and preparative scale packed column supercritical fluid
      chromatography (SFC) have found widespread applicability for chiral separations
      of multiple polar pharmaceutical candidates. However, SFC is rapidly becoming an
      achiral technique. More specifically, ion pair SFC is finding greater utility for
      separation of ionic analytes such as amine salts and organic sulfonates. The key
      to this success is, in part, the incorporation of additives such as
      trifluoroacetic acid and ammonium acetate into the mobile phase in association
      with a wide variety of both bonded silica stationary phases and high purity bare
      silica. Ion pairing SFC coupled with evaporative light scattering detection and
      mass spectrometric detection is presented here for the separation of water
      soluble, uncapped, isomeric peptide pairs that differ in amino acid arrangement.
      The separation is best achieved on either diol-bonded silica or bare silica with
      1-5% (w/w) water as a significant ingredient in the mobile phase. Nitrogenous
      stationary phases such as 2-ethylpyridine, which had been very successful for the
      separation of capped peptides failed to yield the desired separation regardless
      of the mobile phase composition. A HILIC type retention mechanism is postulated
      for the separation of both isomeric uncapped peptide pairs.

PMID- 22386259
TI  - Highly sensitive chiral analysis in capillary electrophoresis with large-volume
      sample stacking with an electroosmotic flow pump.
AB  - To improve the sensitivity in chiral analysis by capillary electrophoresis
      without loss of optical resolution, application of large-volume sample stacking
      with an electroosmotic flow pump (LVSEP) was investigated. Effects of the
      addition of cyclodextrin (CD) into a running solution on the LVSEP
      preconcentration was theoretically studied, where the preconcentration efficiency
      and effective separation length would be slightly increased if the effective
      electrophoretic velocity (v(ep,eff,BGS)) of the analytes was decreased by
      interacting with CD. In LVSEP-CD-modified capillary zone electrophoresis (CDCZE)
      and LVSEP-CD electrokinetic chromatography with reduced v(ep,eff,BGS), up to 1000
      fold sensitivity increases were achieved with almost no loss of resolution. In
      LVSEP-CD-modified micellar electrokinetic chromatography of amino acids with
      increased v(ep,eff,BGS), a 1300-fold sensitivity increase was achieved without
      much loss of resolution, indicating the versatile applicability of LVSEP to many
      separation modes. An enantio-excess (EE) assay was also carried out in LVSEP
      CDCZE, resulting in successful analyses of up to 99.6% EE. Finally, we analyzed
      ibuprofen in urine by desalting with a C18 solid-phase extraction column. As a
      typical result, 250ppb ibuprofen was well concentrated and optically resolved
      with 84.0-86.6% recovery in LVSEP-CDCZE, indicating the applicability of LVSEP to
      real samples containing a large amount of unnecessary background salts.

PMID- 22386260
TI  - Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation
      of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.
AB  - We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are
      potent Pim kinase inhibitors with in vitro antiproliferative activities. In the
      present study, we report the synthesis of new pyrrolocarbazoles substituted at
      the N-10 position. When their ability to inhibit Pim kinase activities were
      evaluated in in vitro assays, we observed that this nitrogen atom can be
      substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when
      we added a fluorescent dansyl group (compound 13), we were able to show that 13
      penetrates the plasma membrane and enters the cytoplasm.

PMID- 22386261
TI  - Photodynamic therapy for choroidal metastasis in 8 cases.
AB  - PURPOSE: To determine the efficacy of photodynamic therapy (PDT) in the treatment
      of choroidal metastasis. DESIGN: Retrospective, interventional case series.
      PARTICIPANTS: Nine tumors in 8 eyes of 8 patients. INTERVENTION: Photodynamic
      therapy using verteporfin at a dose of 6 mg/m(2) body surface area and 689 nm
      diode laser at an intensity of 600 mW/cm(2) for 83 seconds (50 J/cm(2)). MAIN
      OUTCOME MEASURES: Tumor control and best-corrected visual acuity. RESULTS: Nine
      choroidal metastases in 8 eyes were treated with 1 (8 tumors) or 2 (1 tumor)
      sessions of PDT. The mean tumor basal diameter was 7 mm (median, 7 mm [range, 2
      13 mm]), and mean tumor thickness was 2.9 mm (median, 2.9 mm [range, 1.6-4 mm]).
      All 9 tumors were associated with shallow subretinal fluid. After PDT, complete
      control with resolution of subretinal fluid was achieved in 7 tumors (78%), with
      mean tumor thickness reduction of 39% (median, 43% [range, 6%-61%]). Two tumors
      failed to respond to PDT, both requiring plaque radiotherapy. Improvement or
      stabilization of vision was achieved in 7 eyes. Photodynamic therapy-related
      complications included intraretinal hemorrhage in 1 eye. CONCLUSIONS:
      Photodynamic therapy can be an effective alternative for the treatment of
      choroidal metastasis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 22386262
TI  - The incidence of pulmonary embolism (PE) after spinal fusions.
AB  - BACKGROUND: Pulmonary embolism (PE) is a rare but serious event that may occur
      after spinal surgery. OBJECTIVE: To correlate PE incidence after spinal
      arthrodesis with surgical approach, region of spine operated, and primary spinal
      pathology. To identify PE incidence trends in this population. METHODS: The
      Nationwide Inpatient Sample was queried using ICD-9 codes (81.01-81.08) for
      spinal fusion procedures over a 21-year period (1988-2008). Other data points
      included PE occurrence, surgical approach, spinal region, surgical indication,
      and mortality. Multivariate and relational analyses were performed. RESULTS:
      4,505,556 patients were identified and 9530 had PE (incidence=0.2%). PE patients
      had higher odds of combined A/P surgical approaches than posterior approaches
      (OR=1.97; 95% CI=1.66-2.33), and PE incidence was higher in thoracic versus
      cervical or lumbar fusions (OR=2.54; 95% CI=2.14-3.02). PE was more likely with
      vertebral fracture (OR=1.85; 95% CI=1.53-2.23) and SCI with vertebral fracture
      (OR=4.59; 95% CI=3.72-5.70) than without trauma. Between 1988 and 2008, the PE
      incidence remained stable for patients with intervertebral disk degeneration and
      scoliosis, but increased for patients with vertebral fracture, and SCI with
      vertebral fracture. There was greater inpatient mortality with occurrence of a PE
      (OR=12.92; 95% CI=10.55-14.41). CONCLUSION: Although the incidence of PE in
      spinal arthrodesis patients is only 0.2%, there is a higher incidence after
      combined A/P approaches, thoracic procedures, and trauma surgical procedures.
      Despite the overall PE incidence remaining stable since 1988, incidence steadily
      increased among trauma patients. Further research is needed to explain these
      trends, given the context of changing patient populations and improving surgical
      techniques and prophylaxis measures. Greater caution and prophylaxis among trauma
      patients may be warranted.

PMID- 22386263
TI  - Outline of restorative neurology: definition, clinical practice, assessment,
      intervention.
AB  - Rather than focusing on the deficits and lost function caused by upper motor
      neuron lesions or disorders, it is more advantageous to elucidate, in each
      individual, the specific neural functions that remain available, and then, to
      build upon them by designing a treatment protocol to optimize their effectiveness
      and thus improve recovery. The practice of Restorative Neurology is based on
      detailed assessment of the individual patient, the use of neurophysiological
      methods to elucidate and characterize subclinical function and the application of
      interventions that modify neural activity to improve clinical function.

PMID- 22386264
TI  - Longterm remission of more than 5 years in a patient with progressive multifocal
      leucoencephalopathy and sarcoidosis.

PMID- 22386266
TI  - Opening Pandora's Box--the new biology of driver mutations and clonal evolution
      in cancer as revealed by next generation sequencing.
AB  - Recent advances in next generation sequencing have greatly enhanced the scope and
      speed of genomic cancer research. Apart from merely listing identified mutations
      from cancer genomes sequencing, this review will summarize some insights
      specifically focusing on the biology of allele generating cancer driver mutations
      and clonal patterns during tumor evolution. Studies using massively parallel
      sequencing of primary tumor samples and cancer cell lines have identified
      neomorphic alleles and other recurrent mutations in proteins involved in
      chromatin modification and in the regulation of transcription and translation.
      Further studies with deep sequencing of matched primary and metastatic tumors
      have also started to characterize distinct patterns of tumor clonal evolution.
      The development of single cell sequencing is expected to help further elucidate
      tumor clonality and aid the translation of these discoveries into diagnostic and
      therapeutic applications.

PMID- 22386265
TI  - Mechanisms of long range silencing by imprinted macro non-coding RNAs.
AB  - Non-coding (nc) RNA silencing of imprinted genes in extra-embryonic tissues
      provides a good model for understanding an underexamined aspect of gene
      regulation by macro or long ncRNAs, that is their action as long-range cis
      silencers. Numerous long intergenic ncRNAs (lincRNAs) have been recently
      discovered that are thought to regulate gene expression, some of which have been
      associated with disease. The few shown to regulate protein-coding genes are
      suggested to act by targeting repressive or active chromatin marks. Correlative
      evidence also indicates that imprinted macro ncRNAs cause long-range cis
      silencing in placenta by targeting repressive histone modifications to imprinted
      promoters. It is timely, however, to consider alternative explanations consistent
      with the published data, whereby transcription alone could cause gene silencing
      at a distance.

PMID- 22386267
TI  - Analysis of the IL28RA locus as genetic risk factor for multiple sclerosis.
AB  - Recently, we reported an association between a SNP in IL28RA and MS. Here, we
      performed a fine-mapping of the IL28RA locus by genotyping 10 haplotype-tagging
      SNPs in a Basque-Spanish population. In addition, based on shared genetic risk
      loci between autoimmune diseases, a psoriasis-associated SNP located at this
      locus, rs4649203, was genotyped in four independent populations, comprising a
      total of 2582 cases and 2614 controls. We did not find any consistent association
      between IL28RA and MS in these populations, suggesting that, although it may play
      a role in other autoimmune diseases, this gene is unlikely of general relevance
      to MS pathogenesis.

PMID- 22386269
TI  - [Refractory heart failure in a patient treated with bevacizumab].

PMID- 22386268
TI  - B cell maintenance of subcapsular sinus macrophages protects against a fatal
      viral infection independent of adaptive immunity.
AB  - Neutralizing antibodies have been thought to be required for protection against
      acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus
      (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that
      survival upon subcutaneous (s.c.) VSV challenge was independent of neutralizing
      antibody production or cell-mediated adaptive immunity. However, B cells were
      absolutely required to provide lymphotoxin (LT) alpha1beta2, which maintained a
      protective subcapsular sinus (SCS) macrophage phenotype within virus draining
      lymph nodes (LNs). Macrophages within the SCS of B cell-deficient LNs, or of mice
      that lack LTalpha1beta2 selectively in B cells, displayed an aberrant phenotype,
      failed to replicate VSV, and therefore did not produce type I interferons, which
      were required to prevent fatal VSV invasion of intranodal nerves. Thus, although
      B cells are essential for survival during VSV infection, their contribution
      involves the provision of innate differentiation and maintenance signals to
      macrophages, rather than adaptive immune mechanisms.

PMID- 22386270
TI  - [Prolonged mechanical ventilation probability model].
AB  - OBJECTIVE: To design a probability model for prolonged mechanical ventilation
      (PMV) using variables obtained during the first 24 hours of the start of MV.
      DESIGN: An observational, prospective, multicenter cohort study. SCOPE: Thirteen
      Spanish medical-surgical intensive care units. PATIENTS: Adult patients requiring
      mechanical ventilation for more than 24 hours. INTERVENTIONS: None. STUDY
      VARIABLES: APACHE II, SOFA, demographic data, clinical data, reason for
      mechanical ventilation, comorbidity, and functional condition. A multivariate
      risk model was constructed. The model contemplated a dependent variable with
      three possible conditions: 1. Early mortality; 2. Early extubation; and 3. PMV.
      RESULTS: Of the 1661 included patients, 67.9% (n=1127) were men. Age: 62.1+/-16.2
      years. APACHE II: 20.3+/-7.5. Total SOFA: 8.4+/-3.5. The APACHE II and SOFA
      scores were higher in patients ventilated for 7 or more days (p=0.04 and
      p=0.0001, respectively). Noninvasive ventilation failure was related to PMV
      (p=0.005). A multivariate model for the three above exposed outcomes was
      generated. The overall accuracy of the model in the training and validation
      sample was 0.763 (95%IC: 0.729-0.804) and 0.751 (95%IC: 0.672-0.816),
      respectively. The likelihood ratios (LRs) for early extubation, involving a
      cutoff point of 0.65, in the training sample were LR (+): 2.37 (95%CI: 1.77-3.19)
      and LR (-): 0.47 (95%CI: 0.41-0.55). The LRs for the early mortality model, for a
      cutoff point of 0.73, in the training sample, were LR (+): 2.64 (95%CI: 2.01-3.4)
      and LR (-): 0.39 (95%CI: 0.30-0.51). CONCLUSIONS: The proposed model could be a
      helpful tool in decision making. However, because of its moderate accuracy, it
      should be considered as a first approach, and the results should be corroborated
      by further studies involving larger samples and the use of standardized criteria.

PMID- 22386271
TI  - [Severe sepsis and septic shock: everything done, everything to be done].

PMID- 22386272
TI  - Early detection of infant hearing loss in the private health care sector of South
      Africa.
AB  - OBJECTIVE: A national survey of early hearing detection services was undertaken
      to describe the demographics, protocols and performance of early hearing
      detection, referral, follow-up and data management practices in the private
      health care sector of South Africa. METHODS: All private hospitals with obstetric
      units (n=166) in South Africa were surveyed telephonically. This data was
      incorporated with data collected from self-administered questionnaires
      subsequently distributed nationally to audiology private practices providing
      hearing screening at the respective hospitals reporting hearing screening
      services (n=87). Data was analyzed descriptively to yield national percentages
      and frequency distributions and possible statistical associations between
      variables were explored. RESULTS: Newborn hearing screening was available in 53%
      of private health care obstetric units in South Africa of which only 14% provided
      universal screening. Most (81%) of the healthy baby screening programs used only
      otoacoustic emission screening. Auditory brainstem response screening was
      employed by 24% of neonatal intensive care unit screening programs with only 16%
      repeating auditory brainstem response screening during the follow-up screen.
      Consequently 84% of neonatal intensive care unit hearing screening programs will
      not identify auditory neuropathy. A referral rate of less than 5% for diagnostic
      assessments was reported by 80% of universal programs. Follow-up return rates
      were reported to exceed 70% by only 28% of programs. Using multiple methods of
      reminding parents did not significantly increase reported follow-up return rates.
      Data management was mainly paper based with only 10% of programs using an
      electronic database primarily to manage screening data. CONCLUSIONS: A shortage
      of programs and suboptimal and variable protocols for early hearing detection,
      follow-up and data management in existing programs mean the majority of babies
      with hearing loss in the South African private health care sector will not be
      identified early. Newborn hearing screening must be integrated with hospital
      based birthing services, ideally with centralized data management and quality
      control.

PMID- 22386273
TI  - Seizure activity following cochlear implantation: is it the implant?
AB  - OBJECTIVE: Cochlear implantation is a successful method of auditory
      rehabilitation. This procedure has been associated with facial nerve and
      vestibular end-organ stimulation suggesting potential for extra-cochlear
      stimulation. The objectives of this study were to investigate the potential
      relationship between cochlear implantation and seizure activity in the pediatric
      implant population. METHODS: Local Research Ethics Board approval was obtained.
      The Hospital for Sick Children's Cochlear Implant Database from 1998 to 2011 was
      retrospectively reviewed. Based on a multidisciplinary team, patients who
      received a diagnosis of seizure disorder or had been investigated for seizure
      like activity were identified and reviewed. RESULTS: Fifteen children from a
      group of 816 pediatric cochlear implant users were identified as having suspected
      seizure-like activity. Eventually 10 children were found to have seizures based
      on an evaluation by a pediatric neurologist and an electroencephalogram. Of these
      10, only 3 children had new onset of seizures after cochlear implantation and 2
      of these 3 suffered from global developmental delay and other medical
      comorbidities. No definite temporal connection was found between cochlear implant
      use and seizure activity. CONCLUSIONS: Cochlear implantation in the pediatric
      population continues to be a reliable and safe intervention for children. Overall
      the prevalence of post implantation seizure disorders in our population (0.37%)
      is lower than that of the overall population (0.5-1%). The presence of new-onset
      seizure activity following cochlear implantation is unusual and while there are
      theoretic possibilities of how a cochlear implant could be implicated in
      initiating seizures we were unable to find evidence to support this association.

PMID- 22386274
TI  - Clinical outcomes of ventilation tube placement in children with cleft palate.
AB  - OBJECTIVE: The purpose of this study was to investigate the long-term clinical
      outcomes in children with cleft palate. METHODS: One hundred eight patients with
      cleft palate (CP) were investigated. Microscopic observation of the middle ears
      was performed periodically. If chronic otitis media with effusion (OME) was
      diagnosed at 1 year of age or later, ventilation tube (VT) placement was
      performed. The air-filled area of the mastoid air cells was checked on X-rays
      obtained at 1 and 5 years. The data from each measurement were tested
      statistically by the bootstrap method and Wilcoxon's rank-sum test. The clinical
      course from age 6 to the final examination (average 9.42 years) and the language
      development at 5 years were analyzed using data from the medical records of
      individual patients. RESULTS: VT placements were performed at 5 years of age or
      younger in 41 CP patients (82 ears, 38%). About 30% of patients treated by VT
      placement at 5 years of age or younger required myringotomy and/or VT re
      placement at 6 years of age or over. Ninety-five percent of patients who had not
      been treated by VT insertion at 5 years of age or younger showed a favorable
      subsequent clinical course. Patients treated by VT insertion at 5 years of age or
      younger had significantly smaller mastoid air cell areas as measured at 5 years
      of age and also at 1 year of age. No significant difference in language
      development was observed between the CP patients that underwent /did not undergo
      VT placement. CONCLUSIONS: VT placement should be positively undertaken in CP
      children who have small mastoid air cell areas as measured at 1 year of age,
      because an unfavorable prognosis of OME is expected in such patients. It is
      considered that patients treated by VT placement at 5 years of age or younger
      should be carefully followed up for the development of OME even after 6 years of
      age. Thus, measurement of the mastoid air cell area at the age of 1 year is
      useful for determining the therapeutic program.

PMID- 22386275
TI  - Acoustic radiation force impulse imaging predicts postoperative ascites resulting
      from curative hepatic resection for hepatocellular carcinoma.
AB  - BACKGROUND: Measurement of liver stiffness using Virtual Touch Tissue
      Quantification (VTTQ) based on acoustic radiation force impulse imaging reflects
      the degree of hepatic fibrosis and reserve. This prospective study investigated
      how well the VTTQ value predicts the development of postoperative complications
      before curative hepatic resection for hepatocellular carcinoma (HCC). METHODS:
      The study enrolled 50 consecutive patients between February 2009 and October 2010
      whose preoperative VTTQ values were determined before they underwent curative
      hepatic resection for HCC. We assessed the relationship between postoperative
      complications and VTTQ values. RESULTS: The study included 41 (82%) patients with
      chronic hepatitis and 9 (18%) with nonviral cirrhosis. The mean VTTQ value was
      1.60 (m/sec), which correlated with the fibrosis stage (P = .0058). The VTTQ
      value was the only variable correlated with postoperative ascites that did not
      respond to pharmacologic treatment and required invasive management. Univariate
      and subsequent multivariate analyses revealed that the preoperative VTTQ value
      was the only independent risk factor for predicting the development of
      postoperative ascites (cutoff, 1.68 cm/sec; P = .007; odds ratio, 76.481). The
      area under the receiver operating characteristic curve for the diagnosis of
      postoperative ascites using VTTQ values was 0.90, whereas those using the
      aspartate transaminase-to-platelet ratio index and indocyanine green retention
      rate at 15 minutes values were 0.68 and 0.55, respectively. CONCLUSION: These
      data suggest that the VTTQ value is a reliable surrogate marker for predicting
      postoperative ascites before curative hepatic resection for HCC.

PMID- 22386276
TI  - Prognostic significance of tumor deposits in gastric cancer patients who
      underwent radical surgery.
AB  - BACKGROUND: To investigate the prognostic significance of tumor deposits (TDs) in
      gastric cancers patients who underwent radical surgery. METHODS:
      Clinicopathologic and prognostic data from 2998 gastric cancer patients who
      underwent R0 surgery with D2/D3 lymphadenectomy were retrospectively reviewed. A
      TD was defined as discrete foci of tumor found in the perigastric fat or in
      adjacent ligament away from the leading edge of the tumor and showing no evidence
      of residual lymph node tissue, but within the lymph drainage area of the primary
      carcinoma. RESULTS: TDs were detected in 17.8% of patients. TDs were more
      frequently observed in cancers of larger size, of Borrmann type 4, with
      lymphovascular invasion, deeper in depth of invasion, and with extended lymph
      node metastasis. Multivariate analysis confirmed the presence of TDs as 1 of
      independent factors predicting a poorer outcome. When stratified by pN category,
      significant differences in survival were observed between patients with and
      without TDs for those in pN0/pT1-3, pN1/pT3, pN2/pT1-3 and pN3/pT2-3 category,
      but not for those in pT4a and pT4b category. Moreover, for cancers in each pN
      category, the prognosis for patients with TDs in pT1-4a category was similar with
      that of those without TDs in pT4a category, but significantly better than that of
      those with or without TDs in pT4b category. A revised pT category and a revised
      pTNM system were proposed, in which all the cancers with TDs in pT1-4a category
      were incorporated into those without TDs in pT4a category according to the pN
      category. Further analysis revealed the revised pT category and the revised pTNM
      system had better homogeneity, discriminatory ability, and monotonicity of
      gradients than the American Joint Committee on Cancer (AJCC) pT category and the
      AJCC pTNM system, respectively, representing optimum prognostic stratification.
      CONCLUSION: TDs significantly correlated with gastric cancer patients' survival.
      It might be more suitable for TDs to be treated as a form of serosal invasion.
      Consequently, en bloc resection of the primary carcinoma is crucially important,
      and adjuvant chemotherapy should always be considered if TDs have been detected.

PMID- 22386277
TI  - Accuracy of corneal power measurements by a new Scheimpflug camera combined with
      Placido-disk corneal topography for intraocular lens power calculation in
      unoperated eyes.
AB  - PURPOSE: To assess the accuracy of the corneal power measurements with a new
      Scheimpflug camera combined with Placido-disk corneal topography (Sirius)
      (combined Scheimpflug camera-topographer) for intraocular lens (IOL) power
      calculation in unoperated eyes and compare the results with those by a validated
      corneal topographer (Keratron) (validated topographer). SETTING: Private
      practice. DESIGN: Case series. METHODS: Consecutive patients having
      phacoemulsification and in-the-bag IOL implantation were studied. Intraocular
      lens power was calculated using the Hoffer Q, Holladay 1, and SRK/T formulas; the
      axial length, as measured by ultrasound immersion biometry; and 3 corneal power
      measurements: validated topographer simulated keratometry (K); combined
      Scheimpflug camera-topographer simulated K (derived from anterior corneal
      curvature only); combined Scheimpflug camera-topographer mean pupil power
      (derived from anterior and posterior corneal curvatures through ray tracing). The
      prediction error was calculated as the difference between the predicted
      refraction and the refraction measured 1 month postoperatively. RESULTS: When the
      corneal power measurements from the combined Scheimpflug camera-topographer were
      used, the mean absolute error (MAE) ranged between 0.23 diopter (D) +/- 0.24 (SD)
      (simulated K and Hoffer Q formula) and 0.33 +/- 0.23 D (mean pupil power and
      SRK/T formula). There were no statistically significant differences between the
      MAE generated by the simulated Ks of the 2 devices with any of the 3 formulas.
      CONCLUSION: Both corneal power measurements (simulated K and mean pupil power)
      provided by the new combined Scheimpflug camera-topographer were successfully
      entered into third-generation IOL power calculation formulas in unoperated eyes.
      FINANCIAL DISCLOSURE: Dr. Hoffer is the author of the Hoffer Q formula and owns
      the EyeLab, which sells Hoffer Programs. No other author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 22386278
TI  - Successful argon laser photocoagulation of diffuse epithelial ingrowth following
      concomitant persistent pupillary membrane removal and phacoemulsification.
AB  - A 57-year-old woman had concomitant surgery of persistent pupillary membrane
      removal and uneventful phacoemulsification through the same temporal clear
      corneal incision in her left eye. Short axial lengths (right eye, 21.08 mm; left
      eye, 20.39 mm) with shallow angles were noted bilaterally, and other findings
      were not remarkable. The patient experienced angle-closure attacks 3 and 7 months
      postoperatively. At the second angle-closure attack, diffuse epithelial ingrowth
      was observed. The epithelial ingrowth covered the intraocular lens surface in the
      interpupillary area, the iris surface surrounding the pupil, and the temporal
      anterior chamber angle, but did not reach the corneal endothelial incision. After
      observation of iris blanching with laser photocoagulation, argon laser
      photocoagulation was applied to the epithelium covering the iris and angle 7
      times during the following month. The epithelial ingrowth was completely removed
      and did not recur during the 36-month follow-up. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 22386279
TI  - Comparison of force development strategies of spinal manipulation used for
      thoracic pain.
AB  - INTRODUCTION: To date, there is a paucity of comparative analysis of manual
      therapeutic procedures for the treatment of pain in the same spinal region. This
      paper examines the cross correlation of force-time histories across three
      distinct strategies of force production for the same thoracic spine procedure.
      Secondary analysis includes examination of the characteristics that account for
      potential differences. METHODS: A homogeneous sample of 21 male volunteers and
      three clinicians were selected as a convenience sample. The force-time histories
      were recorded using a table mounted force plate (AMTI model number OR6-7-2000,
      London, ON), and cross-correlation analysis was applied by strategy type, for
      analysis between group data. Secondary parameters included: peak force, preload
      force, slope of the thrust, instantaneous loading rate and thrust duration, of
      the total force magnitude. RESULTS: Primary results indicate strong correlations
      among all strategies but with notably different cross-correlation coefficients
      (0.894 <= r <= 0.946) based on individual comparisons. Classical descriptive
      components of the force-time curves (e.g. preload, peak force, slope) for each
      strategy group were examined. Significant differences in the raw data were noted
      on slope and loading rate (adjusted p < 0.01). One strategy of force development
      was significantly different from the others in four of the five characteristics.
      The effects of clinician stature were evaluated by normalizing force to body
      mass. CONCLUSION: Quantitative biomechanical differences in procedures may be
      responsible for differences in outcomes based on the method of treatment
      selected. This data set begins a basis for translational research to assist in
      identifying populations of thoracic spine pain patients for whom one procedure or
      other may be more effective.

PMID- 22386280
TI  - Effects of external pelvic compression on form closure, force closure, and
      neuromotor control of the lumbopelvic spine--a systematic review.
AB  - Optimal lumbopelvic stability is a function of form closure (joint anatomy),
      force closure (additional compressive forces acting across the joints) and
      neuromotor control. Impairment of any of these mechanisms can result in pain,
      instability, altered lumbopelvic kinematics, and changes in muscle strength and
      motor control. External pelvic compression (EPC) has been hypothesised to have an
      effect on force closure and neuromotor control. However, the specific application
      parameters (type, location and force) and hypothesized effects of EPC are
      unclear. Thus, a systematic review was conducted to summarize the in vivo and in
      vitro effects of EPC. Eighteen articles met the eligibility criteria, with
      quality ranging from 33% to 72% based on a modified Downs and Black index. A
      modified van Tulder's rating system was used to ascertain the level of evidence
      synthesised from this review. There is moderate evidence to support the role of
      EPC in decreasing laxity of the sacroiliac joint, changing lumbopelvic
      kinematics, altering selective recruitment of stabilizing musculature, and
      reducing pain. There is limited evidence for effects of EPC on decreasing sacral
      mobility, and affecting strength of muscles surrounding the SIJ, factors which
      require further investigation.

PMID- 22386281
TI  - Radiofrequency thermoablation in locally advanced breast cancer.
AB  - The authors report their experience of 8 cases of breast cancer in six patients,
      treated by radiofrequency thermoablation. Two patients had bilateral breast
      cancer infiltrating the skin. All patients, but one, were alive at two years
      follow-up. The age range was 54-75 years old (median, 71 years old). We observed
      complete regression in one patient, regression with residual scar in two patients
      and partial regression in the remaining three patients. The authors believe that
      radiofrequency, alone or associated with other treatments, is an easy and useful
      alternative for the management of breast cancer, in selected patient who cannot
      undergo surgery or refuse surgical treatment and other treatments.

PMID- 22386282
TI  - Febrile disease in a Bulgarian emigrant with acute renal failure,
      thrombocytopenia, bilateral subconjunctival haemorrhage and hypoxemia.

PMID- 22386283
TI  - Gompertz' survivorship law as an intrinsic principle of aging.
AB  - We defend the hypothesis that life-spanning population survivorship curves, as
      described by Gompertz' law and composed from cross-sectional data (here
      mortality), reflect an intrinsic aging principle active in each subject of that
      population. In other words Gompertz' law reflects aging of a prototypical
      subject, provided minimal (or no) external causes of death (i.e. fatal
      infections, starvation, accidents). Our approach deviates from the traditional
      (exponential) Gompertz' hazard function. For instance, the here formulated
      Gompertz' law accurately describes old-age deceleration of both all-cause
      mortality and the incidence of some ageing-associated cancers, as illustrated for
      the Dutch population. We consider the possibility that the old-age expression and
      progression of cancer and other pathologies becomes suppressed, because of random
      (and exponential) accumulation of damage during life. Gompertz' law may trigger
      new concepts and models describing life-spanning physiological and pathological
      processes of aging. We discuss (and reject) various aging models (e.g. a
      predominant role of individual variations at birth; reliability theory) and point
      to the explanatory potential of network models and systemic regulatory models.

PMID- 22386284
TI  - [Sports purpura].
AB  - Recreational or regular physical and sport activities may be responsible for a
      wide range of cutaneous complications. Among them, "sports purpura" is a peculiar
      symptom that can occur during a large number of sports. "Effort purpura" defines
      any purpura occurring within the context of physical exercise irrespective of its
      cause. Therefore this clinical diagnosis includes various aetiologies. Diagnosis
      of traumatic purpura is often easy if the sport is mentioned in the anamnesis;
      cutaneous exercise - induced vasculitis must be also noted. Purpura can reveal
      systemic diseases or internal haemorrhage, such as spleen rupture, thrombopathies
      or systemic vasculitis, and other effort purpuras must be taken into account,
      including those related to the environment (cold, sun exposure...). Knowledge of
      a physical activity before the occurrence of purpura should be known by
      practitioner to avoid unnecessary and costly explorations in most of the cases.

PMID- 22386285
TI  - [Risk reduction and drug use in detention: study about the detainees of Liancourt
      Penitentiary].
AB  - BACKGROUND: The prison population is drug users. Recent debates around the
      provision of devices to reduce the risks associated with drug use (syringe
      exchange programs and snort kit) lead us to question local practices of the
      prison population. METHOD: An anonymous questionnaire was offered to the prison
      population of the Liancourt penitentiary. The questions addressed the use of
      drugs before and during incarceration, knowledge of HIV and B and C hepatitis
      status, taking an opiate substitution treatment and advice on the implementation
      of syringe exchange programs and snort kit. RESULTS: A percentage of 54.4 of the
      prisoners responded to the questionnaire. An amount of 60.1 % of respondents
      consumed at least one drug before incarceration and 43.6 % of respondents
      consumed at least one drug during their incarceration. Cannabis was the most
      consumed drug before and during incarceration. Barely half of respondents
      reported knowing their HIV and hepatitis B and C status. Over 10 % of respondents
      said they were interesting in establishing needle exchange programs or snort kit.
      DISCUSSION: The prison concentrate drug users and is not a repressive tool of
      efficient risk reduction. The strategies implemented by the medical unit of
      Liancourt prison require adaptations that warrant development of health
      resources. Then, only new tools to reduce risks associated with drug use can be
      established.

PMID- 22386287
TI  - Introduction. Cardiovascular care of the athletic patient.

PMID- 22386286
TI  - A randomized, multicenter, single-blinded trial comparing paclitaxel-coated
      balloon angioplasty with plain balloon angioplasty in drug-eluting stent
      restenosis: the PEPCAD-DES study.
AB  - OBJECTIVES: This study sought to define the impact of paclitaxel-coated balloon
      angioplasty for treatment of drug-eluting stent restenosis compared with uncoated
      balloon angioplasty alone. BACKGROUND: Drug-coated balloon angioplasty is
      associated with favorable results for treatment of bare-metal stent restenosis.
      METHODS: In this prospective, single-blind, multicenter, randomized trial, the
      authors randomly assigned 110 patients with drug-eluting stent restenoses located
      in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated
      balloon angioplasty. Dual antiplatelet therapy was prescribed for 6 months.
      Angiographic follow-up was scheduled at 6 months. The primary endpoint was late
      lumen loss. The secondary clinical endpoint was a composite of cardiac death,
      myocardial infarction attributed to the target vessel, or target lesion
      revascularization. RESULTS: There was no difference in patient baseline
      characteristics or procedural results. Angiographic follow-up rate was 91%.
      Treatment with paclitaxel-coated balloon was superior to balloon angioplasty
      alone with a late loss of 0.43 +/- 0.61 mm versus 1.03 +/- 0.77 mm (p < 0.001),
      respectively. Restenosis rate was significantly reduced from 58.1% to 17.2% (p <
      0.001), and the composite clinical endpoint was significantly reduced from 50.0%
      to 16.7% (p < 0.001), respectively. CONCLUSIONS: Paclitaxel-coated balloon
      angioplasty is superior to balloon angioplasty alone for treatment of drug
      eluting stent restenosis. (PEPCAD DES-Treatment of DES-In-Stent Restenosis With
      SeQuent(r) Please Paclitaxel Eluting PTCA Catheter [PEPCAD-DES]; NCT00998439).

PMID- 22386288
TI  - Exercise-induced cardiac remodeling.
AB  - Early investigations in the late 1890s and early 1900s documented cardiac
      enlargement in athletes with above-normal exercise capacity and no evidence of
      cardiovascular disease. Such findings have been reported for more than a century
      and continue to intrigue scientists and clinicians. It is well recognized that
      repetitive participation in vigorous physical exercise results in significant
      changes in myocardial structure and function. This process, termed exercise
      induced cardiac remodeling (EICR), is characterized by structural cardiac changes
      including left ventricular hypertrophy with sport-specific geometry (eccentric vs
      concentric). Associated alterations in both systolic and diastolic functions are
      emerging as recognized components of EICR. The increasing popularity of
      recreational exercise and competitive athletics has led to a growing number of
      individuals exhibiting these findings in routine clinical practice. This review
      will provide an overview of EICR in athletes.

PMID- 22386289
TI  - Assessment of left ventricular hypertrophy in a trained athlete: differential
      diagnosis of physiologic athlete's heart from pathologic hypertrophy.
AB  - Physiologic LV remodeling in young trained athletes as a consequence of chronic
      training can occasionally mimic certain pathologic conditions associated with
      sudden death, such as HCM. A small but important subset of elite male athletes
      may show a borderline increased LV wall thickness of 13 to 15 mm, which defines a
      gray zone of overlap between the extreme expressions of athlete's heart and a
      mild HCM phenotype. Such diagnostic ambiguity can be resolved by using the
      paradigm of noninvasive parameters including testing with echocardiography (and,
      more recently, with CMR): left atrial and LV chamber dimensions and shape, brief
      periods of deconditioning to alter LV mass, measurement of oxygen consumption and
      diastolic filling, and recognition of familial occurrence of HCM or a pathogenic
      HCM-causing sarcomere mutation. Such distinctions between physiologic/benign
      athlete's heart and HCM, the most common cause of sudden death in the young in
      the United States, can be crucial. The recognition of HCM leads to
      disqualification from intense competitive sports to reduce sudden death risk and,
      when appropriate, permits initiation of therapeutic interventions.

PMID- 22386290
TI  - Evaluation of suspected right ventricular pathology in the athlete.
AB  - Rigorous training remodels the heart of elite endurance athletes to produce the
      phenotype of the "athlete's heart." This remodeling, which advantages cardiac
      performance, creates challenges in the diagnosis of cardiac disorders within this
      population. This is particularly so for right ventricular pathologies because of
      the limited number of studies documenting the impact of training on right
      ventricular remodeling. Although arrhythmogenic right ventricular cardiomyopathy
      is the focus of this review, several other pathologies that may mimic
      arrhythmogenic right ventricular cardiomyopathy, including right ventricular
      outflow tract tachycardia, Wolff-Parkinson-White syndrome, Brugada syndrome,
      pulmonary embolism, cardiac sarcoidosis, myocarditis, and right ventricular
      infarction, are also included. In particular, the electrocardiographic findings
      for each condition are highlighted because this is the most informative and
      easily accessible diagnostic clinical tool.

PMID- 22386291
TI  - Exercise-induced cardiac injury: evidence from novel imaging techniques and
      highly sensitive cardiac troponin assays.
AB  - Prolonged endurance exercise in humans has been associated with an acute
      impairment in diastolic and systolic cardiac function and the release of cardiac
      troponin. In this chapter, we review recent evidence from studies using novel
      echocardiographic parameters and highly sensitive cardiac troponin assays. We
      demonstrate that the mechanics of left and right ventricular functions are
      acutely impaired after completion of prolonged exercise and that this reduction
      in function is likely multifactorial in etiology. However, we highlight that
      exercise-induced cardiac troponin release is not a marker of exercise-induced
      pathology but likely a physiologic response to exercise. Finally, we discuss the
      potential link between prolonged exercise and the increased incidence of cardiac
      pathology in veteran athletes.

PMID- 22386292
TI  - Assessment and management of atherosclerosis in the athletic patient.
AB  - Many patients and physicians correctly associate physical activity with reduced
      cardiovascular morbidity and mortality. Vigorous physical exertion is
      paradoxically associated with a transient increase in the risk of cardiovascular
      events and sudden cardiac death. This review extrapolates data from the general
      population to the management of athletes with symptoms suspicious for coronary
      artery disease or with prior cardiac events. A history to elicit an athlete's
      concerns and symptoms combined with a physical examination should guide the
      decision for preparticipation exercise testing for athletes without prior cardiac
      events. Athletes with established coronary artery disease should receive
      aggressive secondary prevention regimens, with special attention to adverse
      effects that may be unique to this group. There may be benefit in taking time
      away from competitive athletics to allow for stabilization of coronary artery
      disease with cholesterol-lowering therapy and, therefore, reduction of future
      risk. Exercise testing is important for defining risk before the return to
      participation for athletes who have sustained a cardiac event. Many athletes will
      ultimately be able to return to full participation provided they have received
      aggressive therapy and understand the residual risk associated with vigorous
      physical exertion in the setting of coronary artery disease.

PMID- 22386293
TI  - Evaluation and management of arrhythmia in the athletic patient.
AB  - Athletes may present with palpitations, syncope, or arrest resulting in the
      diagnosis of arrhythmia, or screening may result in diagnosis of conditions with
      predisposition to arrhythmia. This chapter focuses on 3 common arrhythmic
      conditions in athletes-atrial fibrillation, premature ventricular contractions
      (PVCs), and the athlete with an implanted device. (1) Atrial fibrillation: most
      studies show that atrial fibrillation is more common in competitive athletes,
      particularly those participating in long-term endurance sports. Postulated
      mechanisms include morphologic changes such as atrial dilatation, autonomic
      changes such as increased vagal tone, or inflammatory changes due to sports
      participation. Treatment options include long-term antiarrhythmic agents, "pill
      in the pocket" medications, or radiofrequency ablation, a highly successful
      procedure in athletes. (2) Premature ventricular contractions: data conflict on
      whether the incidence of PVCs is increased in highly trained individuals. Very
      frequent PVCs in athletes, however, can be a manifestation of underlying heart
      disease, and athletes presenting with PVCs should undergo evaluation. In the
      absence of underlying heart disease, PVCs do not carry a poor prognosis, and US
      guidelines do not recommend restriction from sports. (3) Implanted devices: the
      safety of sports for the athlete with an implanted device is unknown, and current
      guidelines recommend against participation in vigorous competitive sports, based
      on postulated risks including failure to defibrillate and risk of injury. Many
      athletes with defibrillators and pacemakers do participate in sports. Ongoing
      research will better delineate the risks of sports for the athlete with an
      implanted device.

PMID- 22386294
TI  - Aortic root dilatation in athletic population.
AB  - Remodeling of the aortic root may be expected to occur in athletes as a
      consequence of hemodynamic overload associated with exercise training; however,
      there are few data reporting its presence or extent. This review reports the
      current knowledge regarding the prevalence, upper limits, and clinical
      significance of aortic remodeling induced by athletic training. Several
      determinants impact aortic dimension in healthy, nonathletic individuals,
      including height, body size, age, sex, and blood pressure. Of these factors,
      anthropometric variables have the greatest impact. In athletes, the effect of
      exercise training appears to have only a modest additional influence on aortic
      dimension, although previous studies have produced some conflicting results.
      Specifically, data derived from the largest available athletic cohort suggest
      that the most hemodynamically intense endurance disciplines (eg, cycling and
      swimming) are associated with a significant but mild increase in aortic
      dimensions. Power disciplines, instead, (eg, weight lifting, throwing events)
      have only trivial, if any, impact. In contrast, selected data from a different
      athlete population suggest a more significant dimensional aortic remodeling in
      strength-trained individuals. In our experience, the 99th percentile value of
      aortic root diameter corresponds to 40 mm in males and 34 mm in females, which
      can reasonably be considered the upper limits of physiologic aortic root
      remodeling. However, a small proportion of apparently healthy male athletes
      (approximately 1%) show aortic enlargement above the upper limits, in the absence
      of systemic disease (ie, Marfan syndrome). Athletes presenting with aortic
      enlargement may demonstrate a further dimensional increase in midlife leading to
      clinically relevant aortic dilatation. Occasionally, dilation may be severe
      enough to warrant consideration for surgical treatment. Therefore, serial
      clinical and echocardiographic evaluations are recommended in athletes when
      aortic root exceeds the sex-specific thresholds.

PMID- 22386295
TI  - Syncope in the athletic patient.
AB  - Syncope is a common but concerning event in athletic patients. As such, efforts
      must be made to distinguish presyncope from syncope with a critical distinction
      of syncope during exercise and postexercise syncope. Syncope most often occurs
      just after exercise and is usually benign; however, syncope during exercise may
      be a sign of pathologic structural or electrical cardiac issues. Solving this
      diagnostic puzzle mandates a detailed history and examination frequently
      augmented with diagnostic testing and imaging studies. Recommendations for
      treatment and potential restriction from activity also present challenging
      decisions to the health care provider.

PMID- 22386296
TI  - Sudden cardiac death and preparticipation screening: the debate continues-in
      support of electrocardiogram-inclusive preparticipation screening.
AB  - Sudden cardiac death (SCD) is the leading cause of death in young athletes during
      exercise, and there is international agreement among major medical and sporting
      bodies that young athletes should undergo preparticipation cardiovascular
      screening. However, there is currently no universally accepted screening
      protocol, and substantial debate exists about what constitutes the ideal approach
      to preparticipation screening. The primary objective of preparticipation
      screening is the detection of intrinsic structural or electrical cardiovascular
      disorders that predispose an athlete to SCD. Considerable evidence exists
      suggesting that screening athletes with only a history and physical examination
      leaves most athletes with a serious underlying cardiovascular disease undetected
      and, thus, cannot adequately achieve the primary objective of screening.
      Preparticipating cardiovascular screening inclusive of an electrocardiogram (ECG)
      greatly enhances the ability to identify athletes at risk and is the only model
      shown to be cost-effective and may reduce the rate of SCD. The major obstacle to
      ECG screening in the United States is the lack of a physician workforce skilled
      in interpretation of an athlete's ECG. However, recent studies have demonstrated
      a capacity to distinguish physiologic ECG alterations in athletes from findings
      suggestive of underlying pathology that is both feasible and has a low false
      positive rate. Efforts are underway to increase physician education in ECG
      interpretation. After 2 decades debating the proper screening strategy to
      identify athletes at risk, the weight of scientific evidence suggests that a
      screening program inclusive of ECG is the only strategy that merits promotion.

PMID- 22386297
TI  - Preparticipation athletic screening including an electrocardiogram: an unproven
      strategy for prevention of sudden cardiac death in the athlete.
AB  - One of the fundamental principles of evidence-based medicine is that clinical
      practice should be based on evidence derived from sufficiently robust data to
      ensure that the benefits, risks, and costs of an intervention are known. Although
      intuitively appealing, athletic screening programs with routine
      electrocardiograms (ECGs) followed by restriction of at-risk individuals have not
      been demonstrated to be effective in decreasing the inherent risk of athletic
      sudden death. The incremental use of a screening ECG to a history and physical
      examination remains debatable because of insufficient evidence to conclusively
      resolve the issue. Long-term outcomes with a large group of athletes undergoing
      screening and restriction are limited to a small number of observational trials.
      One supports and many do not support ECG screening with athletic restriction of
      at-risk athletes. Although programs and policies to decrease sudden death are
      laudable, they need further evaluation before being implemented on a large-scale
      basis. Currently, athletes are best protected by a strategy of secondary
      prevention with improvements in resuscitation and emergency action plans.

PMID- 22386298
TI  - Cost-effectiveness analysis of pharmacologic treatment of fibromyalgia in Mexico.
AB  - OBJECTIVE: To identify, from the Mexican Public Health System perspective, which
      would be the most cost-effective treatment for patients with Fibromyalgia (FM).
      MATERIAL AND METHODS: A Markov model including three health states, divided by
      pain intensity (absence or presence of mild, moderate or severe pain) and
      considering three-month cycles; costs and effectiveness were estimated for
      amitriptyline (50mg/day), fluoxetine (80 mg/day), duloxetine (120 mg/day),
      gabapentin (900 mg/day), pregabalin (450 mg/day), tramadol/acetaminophen (150
      mg/1300 mg/dia) and amitriptyline/fluoxetine (50mg/80 mg/dia) for the treatment
      of FM. The clinical outcome considered was the annual rate of pain control.
      Probabilities assigned to the model were collected from published literature.
      Direct medical costs for FM treatment were retrieved from the 2006 data of the
      Mexican Institute of Social Security (IMSS) databases and were expressed in 2010
      Mexican Pesos. Probabilistic Sensitivity Analyses were conducted. RESULTS: The
      best pain control rate was obtained with pregabalin (44.8%), followed by
      gabapentin (38.1%) and duloxetine (34.2%). The lowest treatment costs was for
      amitriptyline ($ 9047.01), followed by fluoxetine ($ 10,183.89) and
      amitriptyline/fluoxetine ($ 10,866.01). By comparing pregabalin vs amitriptyline,
      additional annual cost per patient for pain control would be around $ 50.000 and
      $ 75.000 and would result cost-effective in 70% and 80% of all cases.
      CONCLUSIONS: Among all treatment options for FM, pregabalin achieved the highest
      pain control and was cost-effective in 80% of patients of the Mexican Public
      Health System.

PMID- 22386300
TI  - Psychometric properties of the CAST and SDS scales in young adult cannabis users.
AB  - AIM: To assess the validity of two cannabis use severity scales among young
      cannabis users and to evaluate their ability to detect Substance Use Disorders
      (SUD). PARTICIPANTS: 241 volunteers (18-25 years), with a wide spectrum of
      cannabis use in the last 12 months. MEASUREMENTS: The Cannabis Abuse Screening
      Test (CAST) and Severity of Dependence Scale (SDS) were self-administered. The
      Psychiatric Interview for Substance and Mental Disorders (PRISM) was used as gold
      standard for cannabis use disorders according to DSM-IV. Reliability and validity
      were assessed for two different CAST coding algorithms (b-binary and f-full) and
      for the SDS. In addition, the cannabis use diagnostic criteria contained in the
      PRISM were grouped to approximate forthcoming proposed DSM-V criteria to further
      evaluate these scales. FINDINGS: 26.6% (95% CI: 21.0-32.2) of the subjects met
      criteria for cannabis dependence, and 49.0% (95% CI: 42.7-55.3) for cannabis use
      disorders. For both scales internal consistency (Cronbach's alpha>0.71) and test
      retest intraclass correlation coefficients (>0.80) were good. The score 12 in the
      CAST-full discriminated better than others between presence and absence of
      dependence (27.0%; 95% CI: 21.4-32.6) while the score for discrimination of SUD
      was 9 (51.5%; 95% CI: 45.1-57.8). For the SDS the values were 7 (22.0%; 95% CI:
      16.8-27.2) and 3 (64.7%; 95% CI: 58.7-70.8), respectively. According to proposed
      DSM-V criteria, for moderate and severe addiction the values for the CAST-f were
      7 (68.5%; 95% CI: 62.5-74.3) and 12 (27%; 95% CI: 21.3-32.6) and for the SDS, 3
      (65.0%; 95% CI: 58.7-70.8) and 7 (22%; 95% CI: 17.0-34.3), respectively.
      CONCLUSIONS: The CAST and SDS applied to young cannabis users are reliable and
      valid measures to detect cannabis use disorders when compared to both DSM-IV and
      proposed DSM-V criteria.

PMID- 22386299
TI  - [Docetaxel-based systemic chemotherapy in elderly Korean men with castration
      resistant prostate cancer].
AB  - INTRODUCTION: The aim of this study was to determine the efficacy and safety of
      docetaxel-based systemic chemotherapy in elderly patients with castration
      resistant prostate cancer (CRPC). MATERIAL AND METHODS: We retrospectively
      reviewed the clinical records of 36 patients with CRPC who were treated with
      docetaxel-based systemic chemotherapy at a single institution between May 2005
      and April 2010. After screening, 30 patients met the eligibility criteria, and
      were included. Patients were placed into 2 groups: group 1 consisted of 9
      patients aged <70 years, and group 2 consisted of 21 patients aged >=70 years.
      The treatment consisted of prednisolone (5mg) twice daily and docetaxel (75
      mg/m(2)) once every 3 weeks. RESULTS: The median age was 72 years, and the median
      performance status was 0. The median baseline prostate specific antigen (PSA) was
      33.8 ng/mL. The mean number of docetaxel chemotherapy cycles was 5.8. The PSA
      response rate was 48.2%, and the measurable disease response rate was 15.0%, and
      these rates did not differ between the two groups. The median time to PSA
      progression and median overall survival were 6 and 9 months, respectively. Five
      patients experienced grade 3 or higher neutropenia. The drug-related toxicity was
      not different between the two groups. CONCLUSIONS: The response of elderly CRPC
      patients with good performance status to docetaxel-based systemic chemotherapy
      was similar to that of younger patients. Docetaxel-based systemic chemotherapy is
      generally tolerated in elderly patients with good performance status.

PMID- 22386301
TI  - Challenges for modern scientific writing and editorship: have we lost our moral
      compass?

PMID- 22386302
TI  - Break of reciprocity principle due to localized nonlinearities in concrete.
AB  - The effects of localized nonlinearities on the reciprocity principle in the
      context of ultrasounds and nonlinear elasticity are discussed in this paper.
      Experiments will be presented to prove that a localized crack in a concrete beam
      causes a break of reciprocity in the ultrasonic response to a mechanical
      excitation. The link between non-reciprocity and asymmetry in the nonlinear
      response will be demonstrated and discussed as a tool for NonDestructive
      Evaluation.

PMID- 22386303
TI  - The Jack Rabbit chlorine release experiments: implications of dense gas removal
      from a depression and downwind concentrations.
AB  - The Jack Rabbit (JR) field experiment, involving releases of one or two tons of
      pressurized liquefied chlorine and ammonia into a depression, took place in 2010
      at Dugway Proving Ground, Utah, USA. The releases, of duration about 30 s from a
      short pipe at a height of 2m, were directed towards the ground. The dense two
      phase cloud was initially confined in a depression of 2 m depth and 50 m
      diameter. With wind speeds<about 1.5 m s(-1), the cloud stayed in the depression
      for 30-60 min, during which it was slowly detrained and moved downwind. At wind
      speeds>about 1.5 m s(-1), the initial cloud was not well-confined in the
      depression and moved downwind. Formulas suggested by Briggs et al. in 1990 in
      this journal satisfactorily predict the time durations of confinement.
      Sensitivity runs with the SLAB dense gas model show that the effect of a long
      confinement on maximum downwind concentrations is strongest near the depression.
      The model-predicted and observed maximum 20 s chlorine concentrations agree
      within a factor of two most of the time, as long as the release times based on
      Briggs' theory are used.

PMID- 22386304
TI  - Direct electrochemistry and electrocatalysis of hemoglobin immobilized on
      polyacrylamide-P123 film modified glassy carbon electrode.
AB  - A novel organic mesoporous material, polyacrylamide-P123 (PAM-P123) composite
      film, was used to incorporate hemoglobin (Hb) onto the surface of glassy carbon
      (GC) electrode for studying the direct electron transfer of Hb and fabricating a
      sensitive biosensor of H(2)O(2). Compared with inorganic mesoporous material, the
      PAM-P123 composite film has better film-forming property, which is particularly
      useful for preparing modified electrodes on various substrates for voltammetric
      measurements. The cyclic voltammetry of Nafion/Hb/PAM-P123/GC modified electrode
      showed a couple of well-defined and quasi-reversible redox peaks at about 0.317 V
      (vs. SCE) in pH 7.0 phosphate buffer solution. The Nafion/Hb/PAM-P123/GC modified
      electrode showed a fast amperometric response and good stability for the
      detection of hydrogen peroxide. The results indicate that the PAM-P123 film has a
      promising potential in fabricating third-generation electrochemical biosensors.

PMID- 22386305
TI  - Hearing thresholds in children with a congenital CMV infection: a prospective
      study.
AB  - OBJECTIVE: Hearing thresholds in children with a congenital cytomegalovirus
      (cCMV) infection are not always stable. Children can develop late onset hearing
      loss, fluctuations, progression (worsening) and improvement of hearing loss.
      Knowledge about these characteristics is important to understand why long term
      follow up in these children is mandatory. METHODS: We prospectively follow a
      cohort of 154 children with cCMV infection, 68 of which met the inclusion
      criteria of at least 3 hearing evaluations over a period of at least 18 months in
      the absence of other risk factors for hearing loss. In those 68 children we
      evaluated the occurrence of unstable hearing thresholds: late onset hearing loss,
      fluctuations, progression and improvement of hearing loss. RESULTS: Unstable
      hearing thresholds were observed in 29.4% of children with cCMV infection of
      which 19.2% were found in the group of children with ultimately normal hearing
      and in 62.5% of children with sensorineural hearing loss (SNHL) (p=0.0027).
      Fluctuations occurred in 16.2%. Late onset hearing loss occurred in 4.3% of
      children with a normal hearing at birth. In children with SNHL, progression or
      worsening of hearing thresholds occurred in 27.3% and improvement of thresholds
      in 40.9%. Important changes in thresholds only occurred in 13.2% of all children
      and predominantly in children who finally develop SNHL. CONCLUSIONS: Unstable
      hearing thresholds are frequently found in children with cCMV infection and occur
      not only in children who develop hearing losses but also in children who have a
      normal hearing at the last visit. Important changes in hearing thresholds of > 30
      dB are more frequently seen in children who ultimately will develop SNHL.

PMID- 22386306
TI  - [Hepatitis E: molecular virology, epidemiology and pathogenesis].
AB  - Hepatitis E represents a significant proportion of enteric transmitted liver
      diseases and poses a major public health problem, mainly associated with
      epidemics due to contamination of water supplies, especially in developing
      countries. Hepatitis E virus (HEV) is responsible for self-limiting acute liver
      oral-faecal infections. In industrialised countries, acute hepatitis E is
      sporadic, detected in travellers from endemic areas but also in sporadic cases
      with no risk factors. HEV is a non-enveloped virus with a single-stranded RNA
      genome classified into 4 genotypes and a single serotype. Genotypes 1 and 2 only
      infect humans, and are predominant in the developing countries, while 3 and 4 are
      predominant in industrialised countries, and also infect other species of
      mammals, especially pigs, and multiple evidence classifies HEV as a zoonotic
      agent. Some HEV chronic infections have recently been reported in kidney and
      liver transplant patients. The mortality rate of HEV infection is greater than
      hepatitis A. In addition to faecal-oral transmission, parenteral transmission of
      HEV has also been reported. Several vaccines are currently in development. The
      severity of this infection in some groups of patients, especially pregnant women,
      and the occurrence of chronic hepatitis, even with progression to cirrhosis, have
      raised interest in the application of interferon and/or ribavirin therapy.

PMID- 22386307
TI  - Structural characterization of nanoparticles from thermoresponsive poly(N
      isopropylacrylamide)-DNA conjugate.
AB  - Poly(N-isopropylacrylamide) (PNIPAAm) grafted with single-stranded (ss) DNA
      conjugate (PNIPAAm-g-DNA) self-assembles above its lower critical solution
      temperature to form colloidal particles. When the ssDNA within the particle
      hybridizes with its complementary DNA, the particles aggregate above a certain
      threshold of salt concentration with drastically increased turbidity in solution.
      Detailed structural information of the particle was obtained mainly by small
      angle X-ray scattering. The influence of copolymer composition on the morphology
      of particle and non-crosslinking aggregation was examined. The particle consists
      of hydrophobic PNIPAAm core surrounded by hydrophilic DNA strands. The increase
      in DNA fraction brought about a significant decrease in core size, whereas the
      shell thickness little changed and corresponded to the length of DNA. A
      structural model with a sticky potential was applied to the analysis of particle
      aggregate. This analysis provided that the particles aggregate while the coronal
      layers interpenetrate each other. The interaction between the particles was
      quantified in terms of the sticky potential and showed a trend to be influenced
      by the particle size rather than the graft density of DNA strands on the
      particle.

PMID- 22386308
TI  - Production of CaCO3/hyperbranched polyglycidol hybrid films using spray-coating
      technique.
AB  - Biomineralizing organisms employ macromolecules and cellular processing
      strategies in order to produce highly complex composite materials such as nacre.
      Bionic approaches translating this knowledge into viable technical production
      schemes for a large-scale production of biomimetic hybrid materials have met with
      limited success so far. Investigations presented here thus focus on the
      production of CaCO(3)/polymer hybrid coatings that can be applied to huge surface
      areas via reactive spray-coating. Technical requirements for simplicity and cost
      efficiency include a straightforward one-pot synthesis of low molecular weight
      hyperbranched polyglycidols (polyethers of 2,3-epoxy-1-propanol) as a simple
      mimic of biological macromolecules. Polymers functionalized with phosphate
      monoester, sulfate or carboxylate groups provide a means of controlling CaCO(3)
      particle density and morphology in the final coatings. We employ reactive spray
      coating techniques to generate CaCO(3)/hybrid coatings among which vaterite
      composites can be prepared in the presence of sulfate-containing hyperbranched
      polyglycidol. These coatings show high stability and remained unchanged for
      periods longer than 9 months. By employing carboxylate-based hyperbranched
      polyglycidol, it is possible to deposit vaterite-calcite composites, whereas
      phosphate-ester-based hyperbranched polyglycidol leads to calcite composites.
      Nanoindentation was used to study mechanical properties, showing that coatings
      thus obtained are slightly harder than pure calcite.

PMID- 22386309
TI  - Fabrication of one-dimensional Fe3O4/P(GMA-DVB) nanochains by magnetic-field
      induced precipitation polymerization.
AB  - One-dimensional (1D) magnetic Fe(3)O(4)/P(GMA-DVB) peapod-like nanochains have
      been successfully synthesized by magnetic-field-induced precipitation
      polymerization using Fe(3)O(4) as building blocks and P(GMA-DVB) as linker. The
      Fe(3)O(4) microspheres without surface modification can be arranged with the
      direction of the external magnetic field in a line via the dipolar interaction
      between Fe(3)O(4) microspheres and linked permanently via P(GMA-DVB) coating
      during precipitation polymerization. The length of peapod-like nanochains can be
      controlled by magnetic field intensity, and the thickness of polymer shell can be
      tuned by the amount of monomers. Magnetic measurement revealed that these 1D
      peapod-like nanochains showed highly magnetic sensitivity. In the presence of
      magnetic field, 1D magnetic Fe(3)O(4)/P(GMA-DVB) peapod-like nanochains can be
      oriented and aligned along the direction of external magnetic field.

PMID- 22386310
TI  - The medaka zic1/zic4 mutant provides molecular insights into teleost caudal fin
      evolution.
AB  - Teleosts have an asymmetrical caudal fin skeleton formed by the upward bending of
      the caudal-most portion of the body axis, the ural region. This homocercal type
      of caudal fin ensures powerful and complex locomotion and is regarded as one of
      the most important innovations for teleosts during adaptive radiation in an
      aquatic environment. However, the mechanisms that create asymmetric caudal fin
      remain largely unknown. The spontaneous medaka (teleost fish) mutant, Double anal
      fin (Da), exhibits a unique symmetrical caudal skeleton that resembles the
      diphycercal type seen in Polypterus and Coelacanth. We performed a detailed
      analysis of the Da mutant to obtain molecular insight into caudal fin
      morphogenesis. We first demonstrate that a large transposon, inserted into the
      enhancer region of the zic1 and zic4 genes (zic1/zic4) in Da, is associated with
      the mesoderm-specific loss of their transcription. We then show that zic1/zic4
      are strongly expressed in the dorsal part of the ural mesenchyme and thereby
      induce asymmetric caudal fin development in wild-type embryos, whereas their
      expression is lost in Da. Comparative analysis further indicates that the dorsal
      mesoderm expression of zic1/zic4 is conserved in teleosts, highlighting the
      crucial role of zic1/zic4 in caudal fin morphogenesis.

PMID- 22386311
TI  - Enterocyte microvillus-derived vesicles detoxify bacterial products and regulate
      epithelial-microbial interactions.
AB  - The continuous monolayer of intestinal epithelial cells (IECs) lining the gut
      lumen functions as the site of nutrient absorption and as a physical barrier to
      prevent the translocation of microbes and associated toxic compounds into the
      peripheral vasculature. IECs also express host defense proteins such as
      intestinal alkaline phosphatase (IAP), which detoxify bacterial products and
      prevent intestinal inflammation. Our laboratory recently showed that IAP is
      enriched on vesicles that are released from the tips of IEC microvilli and
      accumulate in the intestinal lumen. Here, we show that these native "lumenal
      vesicles" (LVs) (1) contain catalytically active IAP that can dephosphorylate
      lipopolysaccharide (LPS), (2) cluster on the surface of native lumenal bacteria,
      (3) prevent the adherence of enteropathogenic E. coli (EPEC) to epithelial
      monolayers, and (4) limit bacterial population growth. We also find that IECs
      upregulate LV production in response to EPEC and other Gram-negative pathogens.
      Together, these results suggest that microvillar vesicle shedding represents a
      novel mechanism for distributing host defense machinery into the intestinal lumen
      and that microvillus-derived LVs modulate epithelial-microbial interactions.

PMID- 22386312
TI  - Protein synthesis during sleep consolidates cortical plasticity in vivo.
AB  - Sleep consolidates experience-dependent brain plasticity, but the precise
      cellular mechanisms mediating this process are unknown [1]. De novo cortical
      protein synthesis is one possible mechanism. In support of this hypothesis, sleep
      is associated with increased brain protein synthesis [2, 3] and transcription of
      messenger RNAs (mRNAs) involved in protein synthesis regulation [4, 5]. Protein
      synthesis in turn is critical for memory consolidation and persistent forms of
      plasticity in vitro and in vivo [6, 7]. However, it is unknown whether cortical
      protein synthesis in sleep serves similar functions. We investigated the role of
      protein synthesis in the sleep-dependent consolidation of a classic form of
      cortical plasticity in vivo (ocular dominance plasticity, ODP; [8, 9]) in the cat
      visual cortex. We show that intracortical inhibition of mammalian target of
      rapamycin (mTOR)-dependent protein synthesis during sleep abolishes consolidation
      but has no effect on plasticity induced during wakefulness. Sleep also promotes
      phosphorylation of protein synthesis regulators (i.e., 4E-BP1 and eEF2) and the
      translation (but not transcription) of key plasticity related mRNAs (ARC and
      BDNF). These findings show that sleep promotes cortical mRNA translation.
      Interruption of this process has functional consequences, because it abolishes
      the consolidation of experience in the cortex.

PMID- 22386313
TI  - Figure tracking by flies is supported by parallel visual streams.
AB  - Visual figures may be distinguished based on elementary motion or higher-order
      non-Fourier features, and flies track both. The canonical elementary motion
      detector, a compact computation for Fourier motion direction and amplitude, can
      also encode higher-order signals provided elaborate preprocessing. However, the
      way in which a fly tracks a moving figure containing both elementary and higher
      order signals has not been investigated. Using a novel white noise approach, we
      demonstrate that (1) the composite response to an object containing both
      elementary motion (EM) and uncorrelated higher-order figure motion (FM) reflects
      the linear superposition of each component; (2) the EM-driven component is
      velocity-dependent, whereas the FM component is driven by retinal position; (3)
      retinotopic variation in EM and FM responses are different from one another; (4)
      the FM subsystem superimposes saccadic turns upon smooth pursuit; and (5) the two
      systems in combination are necessary and sufficient to predict the full range of
      figure tracking behaviors, including those that generate no EM cues at all. This
      analysis requires an extension of the model that fly motion vision is based on
      simple elementary motion detectors and provides a novel method to characterize
      the subsystems responsible for the pursuit of visual figures.

PMID- 22386314
TI  - Predictive properties of visual adaptation.
AB  - What humans perceive depends in part on what they have previously experienced.
      After repeated exposure to one stimulus, adaptation takes place in the form of a
      negative correlation between the current percept and the last displayed stimuli.
      Previous work has shown that this negative dependence can extend to a few minutes
      in the past, but the precise extent and nature of the dependence in vision is
      still unknown. In two experiments based on orientation judgments, we reveal a
      positive dependence of a visual percept with stimuli presented remotely in the
      past, unexpectedly and in contrast to what is known for the recent past. Previous
      theories of adaptation have postulated that the visual system attempts to
      calibrate itself relative to an ideal norm or to the recent past. We propose
      instead that the remote past is used to estimate the world's statistics and that
      this estimate becomes the reference. According to this new framework, adaptation
      is predictive: the most likely forthcoming percept is the one that helps the
      statistics of the most recent percepts match that of the remote past.

PMID- 22386316
TI  - Mind maps: Enhancing midwifery education.
AB  - Educationalists need to think outside the box to facilitate students to learn key
      information essential for professional practice. The use of mind maps
      incorporated into an assessment strategy and programme is an innovative way of
      facilitating students to understand key information. Mind maps have the potential
      to provide students with a strategy for retaining information, integrating
      critical thinking and problem solving skills. This article reviews the current
      discussion on mind maps and discusses the integration of mind maps into a
      component of an assessment strategy. 

PMID- 22386315
TI  - Pseudopod growth and evolution during cell movement is controlled through
      SCAR/WAVE dephosphorylation.
AB  - BACKGROUND: SCAR/WAVE is a principal regulator of pseudopod growth in crawling
      cells. It exists in a stable pentameric complex, which is regulated at multiple
      levels that are only beginning to be understood. SCAR/WAVE is phosphorylated at
      multiple sites, but how this affects its biological activity is unclear. Here we
      show that dephosphorylation of Dictyostelium SCAR controls normal pseudopod
      dynamics. RESULTS: We demonstrate that the C-terminal acidic domain of most
      Dictyostelium SCAR is basally phosphorylated at four serine residues. A small
      amount of singly phosphorylated SCAR is also found. SCAR phosphorylation site
      mutants cannot replace SCAR's role in the pseudopod cycle, though they rescue
      cell size and growth. Unphosphorylatable SCAR is hyperactive-excessive
      recruitment to the front results in large pseudopods that fail to bifurcate
      because they continually grow forward. Conversely, phosphomimetic SCAR is weakly
      active, causing frequent small, disorganized pseudopods. Even in its regulatory
      complex, SCAR is normally held inactive by an interaction between the
      phosphorylated acidic and basic domains. Loss of basic residues complementary to
      the acidic phosphosites yields a hyperactive protein similar to
      unphosphorylatable SCAR. CONCLUSIONS: Regulated dephosphorylation of a fraction
      of the cellular SCAR pool is a key step in SCAR activation during pseudopod
      growth. Phosphorylation increases autoinhibition of the intact complex.
      Dephosphorylation weakens this interaction and facilitates SCAR activation but
      also destabilizes the protein. We show that SCAR is specifically dephosphorylated
      in pseudopods, increasing activation by Rac and lipids and supporting positive
      feedback of pseudopod growth.

PMID- 22386317
TI  - Incidence of fractures causing hospitalisation in prostate cancer patients:
      results from the population-based PCBaSe Sweden.
AB  - BACKGROUND: Prostate cancer patients have an increased risk of fractures as a
      consequence of skeletal metastases and osteoporosis induced by endocrine
      treatment. Data on incidence of fractures and risks in subgroups of men with
      prostate cancer are sparse. Our aim with this study is to report the risk of
      fractures among men with prostate cancer in a nationwide population-based study.
      PATIENTS AND METHODS: We identified 76,600 Swedish men diagnosed with prostate
      cancer 1997-2006 in the Prostate Cancer Data Base (PCBaSe) Sweden and compared
      the occurrence of fractures requiring hospitalisation with the Swedish male
      population. RESULTS: Only men treated with gonadotropin releasing-hormone (GnRH)
      agonists or orchiectomy had increased incidence and increased relative risk of
      fractures requiring hospitalisation. Men treated with GnRH agonists had 9.8 and
      6.3/1000 person-years higher incidence of any fracture and hip fracture requiring
      hospitalisation than the general population. The corresponding increases in
      incidence for men treated with orchiectomy were 16 and 12/1000 person-years,
      respectively. Men treated with orchiectomy, GnRH agonists, and antiandrogen
      monotherapy, had SIR for hip fracture of 2.0 (95% Confidence Interval 1.8-2.2),
      1.6 (95% CI 1.5-1.8) and 0.9 (95% CI 0.7-1.1), respectively. Men treated with a
      curative intent (radical prostatectomy or radiotherapy) or managed with
      surveillance had no increased risk of fractures. Older men had the highest
      incidence of fractures while younger men had the highest relative risk.
      CONCLUSION: Prostate cancer patients treated with GnRH agonists or orchiectomy
      have significantly increased risk of fractures requiring hospitalisation while
      patients treated with antiandrogen monotherapy had no increase in such fractures.
      In absolute terms the excess risk in men treated with GnRH agonists corresponded
      to almost 10 extra fractures leading to hospitalisation per 1000 patient-years.
      Effects on bone density should be considered for men on long-term endocrine
      treatment. Unwarranted use of orchiectomy and GnRH agonists should be avoided.

PMID- 22386319
TI  - Ocular vestibular-evoked myogenic potentials via bone-conducted vibration in
      children.
AB  - OBJECTIVE: This study utilized bone-conducted vibration (BCV) stimuli for
      eliciting ocular vestibular-evoked myogenic potentials (oVEMPs) to assess the
      vestibulo-ocular reflex (VOR) system in healthy children and adults. METHODS:
      Fifteen healthy children aged 3-14 years and 18 healthy adults aged 24-28 years
      underwent oVEMP testing. Structural factors such as body weight, body height and
      body mass index were measured for each healthy subject. RESULTS: All healthy
      children and adults presented clear oVEMPs, bilaterally. The characteristic
      parameters (latencies and amplitude) of oVEMPs did not significantly differ
      between children and adults. The mean interaural (y-axis) acceleration magnitudes
      for eliciting oVEMPs were 0.37 +/- 0.12 g for children and 0.41 +/- 0.20 g for
      adults, a non-significant difference. As stimulation intensity increased
      stepwise, interaural acceleration magnitude increased correspondingly, leading to
      early nI latency and large nI-pI amplitude of oVEMPs. However, no structural
      factor was statistically correlated with interaural acceleration magnitude.
      CONCLUSION: When children aged >3 years, the simple and quick oVEMP test via BCV
      stimulation can be used for investigating the integrity of the VOR system, with
      the characteristic parameters (latencies and amplitude) unaffected by structural
      factors. SIGNIFICANCE: Establishing the norm of oVEMP is essential for diagnosing
      VOR deficit in children aged >3 years.

PMID- 22386318
TI  - Coding region polyadenylation generates a truncated tRNA synthetase that counters
      translation repression.
AB  - Posttranscriptional regulatory mechanisms superimpose "fine-tuning" control upon
      "on-off" switches characteristic of gene transcription. We have exploited
      computational modeling with experimental validation to resolve an anomalous
      relationship between mRNA expression and protein synthesis. The GAIT (gamma
      interferon-activated inhibitor of translation) complex repressed VEGF-A synthesis
      to a low, constant rate independent of VEGF-A mRNA expression levels. Dynamic
      model simulations predicted an inhibitory GAIT-element-interacting factor to
      account for this relationship and led to the identification of a truncated form
      of glutamyl-prolyl tRNA synthetase (EPRS), a GAIT constituent that mediates
      binding to target transcripts. The truncated protein, EPRS(N1), shields GAIT
      element-bearing transcripts from the inhibitory GAIT complex, thereby dictating a
      "translational trickle" of GAIT target proteins. EPRS(N1) mRNA is generated by
      polyadenylation-directed conversion of a Tyr codon in the EPRS-coding sequence to
      a stop codon (PAY(*)). Genome-wide analysis revealed multiple candidate PAY(*)
      targets, including the authenticated target RRM1, suggesting a general mechanism
      for production of C terminus-truncated regulatory proteins.

PMID- 22386320
TI  - Cost-effectiveness of intraoperative neurophysiological monitoring for spinal
      surgeries: beginning steps.

PMID- 22386321
TI  - Early effect of tacrolimus in improving excitation-contraction coupling in
      myasthenia gravis.
AB  - OBJECTIVES: Tacrolimus (FK506) is a macrolide T-cell immunomodulator used to
      treat myasthenia gravis (MG). Besides immunosuppression, tacrolimus has been
      reported to have the potential to increase muscle strength by enhancing ryanodine
      receptor (RyR) function. However, few attempts have been made to demonstrate the
      early effect of tacrolimus as an RyR enhancer in clinical investigation. METHODS:
      In 20 MG patients, masseteric compound muscle action potential (CMAP) and
      mandibular movement-related potentials (MRPs) were recorded simultaneously after
      stimulating the trigeminal motor nerve with a needle electrode. The excitation
      contraction (E-C) coupling time (ECCT) was calculated by the latency difference
      between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet.
      Serial assessments of % decrement in masseteric repetitive nerve stimulation
      (RNS), ECCT and bite force were performed before and within 4 weeks of tacrolimus
      (3 mg day(-1)) treatment. The median (mean, range) interval of assessment was 2
      (2.4, 1-4) weeks. We also measured serum antibodies against RyR, acetylcholine
      receptor and muscle-specific receptor tyrosine kinase. RESULTS: Bite force
      increased after tacrolimus treatment accompanying clinical improvement assessed
      by Myasthenia Gravis Foundation of America classification, but the bite force
      difference did not reach statistical significance. Wilcoxon matched-pairs signed
      ranks test detected a significant ECCT shortening in 12 patients assessed after 1
      2 weeks of tacrolimus treatment as well as in eight patients assessed after 3-4
      weeks. In contrast, masseteric CMAP and % decrement showed no significant changes
      after short-term tacrolimus treatment. CONCLUSIONS: Tacrolimus induces ECCT
      shortening accompanying clinical improvement despite no improvement in %
      decrement within 2 weeks. SIGNIFICANCE: This early effect of tacrolimus may imply
      a pharmacological enhancement of RyR function to improve E-C coupling in MG.

PMID- 22386322
TI  - HIV associated dementia: role for neurosteroids.
AB  - HIV associated dementia (HAD), is a neuronal complication of HIV infection and
      causes cognitive and motor impairment. The cognitive decline in HAD is due to
      widespread synaptic loss than neuronal loss. The neurotoxicity in HAD is caused
      by activation of NMDA receptors by HIV-proteins but the exact mechanism of the
      synaptic loss is yet to be determined. This article explores a novel
      pathomechanism for the observed synaptic loss. The HIV-proteins augment NMDA
      mediated increase of intracellular Ca(2+) in neurons which activates nNOs for
      Nitric Oxide (NO) synthesis. The NO activates MAPK and phosphorylates Microtubule
      associated protein-2(MAP2) at specific sites causing conformational changes,
      microtubular disassembly and promote MAP2 degradation by the ubiquitin-proteosome
      pathway. Under physiological conditions Ca(2+) signaling increases cholesterol
      transport into mitochondria for steroidogenesis by the CYP11A1. The neurosteroid
      pregnenolone binds to MAP2 and causes inhibition of phosphorylation, increase in
      microtubule assembly and decrease MAP2 degradation. The NO can inhibits CYP11A1
      in a concentration dependent manner and reduces steroidogeneisis. There is a
      upregulation of NO production in HAD from HIV infected microglia and astrocytes
      which cross neuronal membrane and increase intracellular NO. This can cause
      profound inhibition of steroidogenesis in the brain, increase MAP2 degradation
      and synaptic loss in presence of HIV-proteins.

PMID- 22386323
TI  - Profile of biochemical traits influencing tenderness of muscles from the beef
      round.
AB  - The objective of this study was to define the biochemical differences that govern
      tenderness and palatability of economically important muscles from the beef round
      using cuts with known tenderness differences. At 24h postmortem, the longissimus
      dorsi (LD), gracillus (GR), adductor (AD), semimembranosus (SM), sartorius (SAR),
      vastus lateralis (VL), and vastus intermedius (VI) muscles were removed from ten
      market weight beef cattle. Sensory and biochemical characteristics were
      determined in each cut and compared with the LD. The GR, SAR and VI had sensory
      traits similar to the LD while the SM, AD and VL differed. The GR, SAR, AD, and
      SM all had multiple biochemical characteristics similar to the LD, while the VI
      and AD had numerous biochemical differences. While no one biochemical
      characteristic can be used to predict tenderness across all muscles, analysis of
      the biochemical characteristics revealed that in most beef round cuts postmortem
      proteolysis provided a good indication of the tenderization occurring during
      aging.

PMID- 22386324
TI  - The microbiological conditions of carcasses from large game animals in Italy.
AB  - This study investigates the microbiological conditions of large game animal
      carcasses following evisceration. Carcasses of animals (N=291) hunted in the
      Upper Susa Valley (Italian Alps) were analysed for pH, Aerobic Viable Count
      (AVC), Enterobacteriaceae, Yersinia spp., Listeria monocytogenes and Salmonella
      spp. After shooting, evisceration occurred within 60 min in 90.7% of animals and
      sampling within 90 min in 88.3% of animals. Mean pH values (5.97: ruminants;
      5.77: wild boar) were similar to those of regularly slaughtered domestic species.
      AVC values were highest in animals shot in the abdomen. Within species, AVC and
      Enterobacteriaceae values did not differ across different shooting
      evisceration/sampling times. However, these counts exceeded 5 and 2.5 log,
      respectively, in 18% of wild boar and 39% of ruminants; the highest values were
      detected in wild boar. No pathogens were detected in any species. These results
      reveal inadequate hygiene in game meat handling/harvesting, implicating the need
      for improved practices.

PMID- 22386325
TI  - [Management of massive hemoptysis].
AB  - Massive hemoptyses are serious clinical conditions that can quickly jeopardize
      the vital prognosis. The major risk is asphyxiation, due to the bleeding into the
      tracheobronchial tree. The clinician should provide in parallel support for
      diagnosis and treatment, locating the bleeding but also finding its cause. Such
      patients should be cared for by a multidisciplinary team, having quick access to
      an important technical support. The association fiberoptic bronchoscopy-chest CT
      scan seems to be the most effective to locate and identify the cause of the
      bleeding. The development of bronchial artery embolization has revolutionized the
      management of these patients, replacing surgery in many of its indications. The
      latter still keeps a place in the management of these patients. Indeed, it is the
      main etiological treatment, preventing the vast majority of recidivism. It is
      absolutely indicated in the treatment of bleeding from the pulmonary vessels, and
      in case of failure of other techniques. It should be performed whenever possible
      away from the episode of hemoptysis, in order to minimize the operative risk.

PMID- 22386326
TI  - Endemic mycoses: overlooked causes of community acquired pneumonia.
AB  - The endemic mycoses are important but often overlooked causes for community
      acquired pneumonia. Delays in recognition, diagnosis and proper treatment often
      lead to disastrous outcomes. This topic is not usually discussed in reviews and
      guidelines addressing the subject of community acquired pneumonia. In this review
      we discuss the three major endemic mycoses in North America that present as
      community acquired pneumonias; Coccidioidomycosis, Histoplasmosis and
      Blastomycosis. We discuss their epidemiology, clinical presentations, methods of
      diagnosis and current treatment strategies.

PMID- 22386327
TI  - Phylogenetic analysis of the bacterial community in a full scale autothermal
      thermophilic aerobic digester (ATAD) treating mixed domestic wastewater sludge
      for land spread.
AB  - The bacterial community associated with a full scale autothermal thermophilic
      aerobic digester (ATAD) treating sludge, originating from domestic wastewater and
      destined for land spread, was analysed using a number of molecular approaches
      optimised specifically for this high temperature environment. 16S rDNA genes were
      amplified directly from sludge with universally conserved and Bacteria-specific
      rDNA gene primers and a clone library constructed that corresponded to the late
      thermophilic stage (t = 23 h) of the ATAD process. Sequence analyses revealed
      various 16S rDNA gene sequence types reflective of high bacterial community
      diversity. Members of the bacterial community included alpha- and beta
      Proteobacteria, Actinobacteria with High G + C content and Gram-Positive bacteria
      with a prevalence of the Firmicutes (Low G + C) division (class Clostridia and
      Bacillus). Most of the ATAD clones showed affiliation with bacterial species
      previously isolated or detected in other elevated temperature environments, at
      alkaline pH, or in cellulose rich environments. Several phylotypes associated
      with Fe(III)- and Mn(IV)-reducing anaerobes were also detected. The presence of
      anaerobes was of interest in such large scale systems where sub-optimal aeration
      and mixing is often the norm while the presence of large amounts of capnophiles
      suggest the possibility of limited convection and entrapment of CO(2) within the
      sludge matrix during digestion. Comparative analysis with organism identified in
      other ATAD systems revealed significant differences based on optimised
      techniques. The abundance of thermophilic, alkalophilic and cellulose-degrading
      phylotypes suggests that these organisms are responsible for maintaining the
      elevated temperature at the later stages of the ATAD process.

PMID- 22386328
TI  - A comparison of cake properties in traditional and turbulence promoter assisted
      microfiltration of particulate suspensions.
AB  - The use of turbulence promoter can effectively enhance the permeate flux in
      crossflow microfiltration (CFMF) of particulate suspensions. Flux enhancement
      which is generally attributed to the reduction in cake thickness, however, has
      still not been clearly understood. In this study, the effects of turbulence
      promoter on cake properties (thickness, porosity and particle size) were
      investigated during CFMF of calcium carbonate suspension. It indicates that
      turbulence promoter has important effects on cake properties that directly affect
      the cake resistance. The significant reduction in thickness and slight increase
      in porosity are positive to reduce the cake resistance. The remarkable decrease
      in particle size is the negative effect due to the increased specific resistance
      of a cake. As a whole, the overall cake resistance is still diminished by
      turbulence promoter and therefore permeate flux is improved. The theoretical
      calculation of cake resistance shows a good consistence with the experimental
      result. The cake properties in both cases (using a turbulence promoter or not)
      almost exhibit the similar trends under various operating conditions.
      Differently, the use of turbulence promoter can greatly alleviate the effects of
      transmembrane pressure or feed concentration on growth of cake layer and
      intensify the effects of inlet velocity on diminishing the particle deposition.

PMID- 22386329
TI  - Assessment of the formation of inorganic oxidation by-products during the
      electrocatalytic treatment of ammonium from landfill leachates.
AB  - This work investigates the formation of oxidation by-products during the
      electrochemical removal of ammonium using BDD electrodes from wastewaters
      containing chlorides. The influence of the initial chloride concentration has
      been experimentally analyzed first, working with model solutions with variable
      ammonium concentration and second, with municipal landfill leachates. Two
      different levels of chloride concentration were studied, i) low chloride
      concentrations ranging between 0 and 2000 mg/L and, ii) high chloride
      concentrations ranging between 5000 and 20,000 mg/L. Ammonium removal took place
      mainly via indirect oxidation leading to the formation of nitrogen gas and
      nitrate as the main oxidation products; at high chloride concentration the
      formation of nitrogen gas and the rate of ammonium removal were both favored.
      However, chloride was also oxidized during the electrochemical treatment leading
      to the formation of free chlorine responsible of the ammonium oxidation, together
      with undesirable products such as chloramines, chlorate and perchlorate.
      Chloramines appeared during the treatment but they reached a maximum and then
      started decreasing, being totally removed when high chloride concentrations were
      used. With regard to the formation of chlorate and perchlorate once again the
      concentration of chloride exerted a strong influence on the formation kinetics of
      the oxidation by-products and whereas at low chloride concentrations, chlorate
      appeared like an intermediate compound leading to the formation of perchlorate,
      at high chloride concentrations chlorate formation was delayed significantly and
      perchlorate was not detected during the experimental time. Thus this work
      contributes first to the knowledge of the potential hazards of applying the
      electro-oxidation technology as an environmental technology to deal with ammonium
      oxidation under the presence of chloride and second it reports efficient
      conditions that minimize or even avoid the formation of undesirable by-products.

PMID- 22386330
TI  - Catalysis of copper corrosion products on chlorine decay and HAA formation in
      simulated distribution systems.
AB  - This study investigated the effect of copper corrosion products, including
      Cu(II), Cu(2)O, CuO and Cu(2)(OH)(2)CO(3), on chlorine degradation, HAA
      formation, and HAA speciation under controlled experimental conditions. Chlorine
      decay and HAA formation were significantly enhanced in the presence of copper
      with the extent of copper catalysis being affected by the solution pH and the
      concentration of copper corrosion products. Accelerated chlorine decay and
      increased HAA formation were observed at pH 8.6 in the presence of 1.0 mg/L
      Cu(II) compared with that observed at pH 6.6 and pH 7.6. Further investigation of
      chlorine decay in the presence of both Suwannee River NOM and Cu(II) indicated
      that an increased reactivity of NOM with dissolved and/or solid surface
      associated Cu(II), rather than chlorine auto-decomposition, was a primary reason
      for the observed rapid chlorine decay. Copper corrosion solids [Cu(2)O, CuO,
      Cu(2)(OH)(2)CO(3)] exhibited catalytic effects on both chlorine decay and HAA
      formation. Contrary to the results observed when in the absence of copper
      corrosion products, DCAA formation was consistently predominant over other HAA
      species in the presence of copper corrosion products, especially at neutral and
      high pH. This study improves the understanding for water utilities and households
      regarding chlorine residuals and HAA concentrations in distribution systems, in
      particular once the water reaches domestic plumbing where copper is widely used.

PMID- 22386331
TI  - Antiplatelet therapies are associated with hematoma enlargement and increased
      mortality in intracranial hemorrhage.
AB  - OBJECTIVE: Antiplatelet therapy (AT) is increasingly used for treating or
      preventing vascular diseases, especially as a consequence of population aging.
      However, the risks may sometimes outweigh the benefits, mostly in relation to
      intracranial hemorrhage (ICH). Our aim was to determine whether AT is associated
      with hematoma enlargement and increased mortality in ICH. DESIGN: A prospective,
      observational cohort study. SETTING: The Intensive Care Unit (ICU) of Arrixaca
      University Hospital (Murcia, Spain). PATIENTS: We studied 156 patients admitted
      with non-traumatic ICH between January 2006 and August 2008. INTERVENTIONS: None.
      MAIN VARIABLES: Demographic data, medical history and clinical and laboratory
      parameters were recorded, along with hematoma volume upon admission and after
      24h, and mortality. RESULTS: A total of 37 patients (24%) received AT. These
      subjects were older (69 +/- 11 vs. 60 +/- 15 years, p=0.001) and more frequently
      diabetic (38% vs. 15%, p=0.003) than those without AT. We detected no difference
      in hematoma volume upon admission between the two groups, though the volume was
      significantly greater after 24h in the AT group (66.7 [IQR 42-110] vs. 27 [4.4
      64.6]cm(3), p=0.03), irrespective of surgical intervention. Moreover, hematoma
      volume increased by more than a third in AT-users (69% vs. 33%, p=0.002), and AT
      was the only significant predictor of hematoma enlargement. Patients on AT also
      had higher mortality during their ICU stay (78% vs. 45%, p<0.001). In addition,
      of the patients with hematoma enlargement, over one-third had higher overall
      mortality (62.5 vs. 28.8%, p=0.001). Independent risk factors for death were the
      Glasgow Coma Scale score, blood glucose upon admission, and AT. CONCLUSIONS: Our
      results show an association between AT and subsequent hematoma enlargement, as
      well as increased mortality in patients presenting with ICH who were receiving
      AT.

PMID- 22386332
TI  - Renal replacement therapy in the critical patient: treatment variation over time.
AB  - OBJECTIVES: To analyze the evolution of patients subjected to renal replacement
      therapy (RRT), and to determine risk factors associated with mortality and the
      recovery of renal function. DESIGN: A prospective, observational study of
      critically ill patients. SETTING: Clinical-surgical Intensive Care Unit (ICU) of
      Sabadell Hospital (Spain). PATIENTS: Inclusion of all patients treated in our
      Unit due to acute renal failure (ARF) requiring RRT. PRIMARY VARIABLES OF
      INTEREST: We recorded epidemiological data, severity using the APACHE II score,
      days of the technique, ICU mortality, and renal function recovery. The study
      period was divided into 2 parts: part 1 (2000-2004) and part 2 (2005-2009). The 2
      periods were compared using the Student t-test for continuous variables and the
      chi-squared test for categorical variables. Multiple regression analysis was
      performed to determine the risk factors for mortality and recovery of renal
      function. RESULTS: A total of 304 patients were treated. Sepsis was the main
      etiology of ARF (61%), involving principally respiratory and abdominal foci. In
      the second period the convective technique and community-acquired ARF were far
      more prevalent than in the first period. There were fewer days of therapy in the
      second period (19.7 versus 12.3 days; P=.015). Total ICU mortality was 52.3%,
      with a decrease in the last period (61.9% to 45.5%: P=.003). The risk factors
      associated to mortality were creatinine upon admission (odds ratio [OR] 0.77; 95%
      confidence interval [95%CI] 0.61-0.97) and treatment with IHD alone (OR 0.37,
      95%CI 0.16-0.87). Survivors had normal renal function at ICU discharge in 56.7%
      of the cases in the second period, vs in 72.9% in the first period, with more
      patients subjected to IHD in the second period (10.4% versus 26.8%). The factors
      related to the recovery of renal function were creatinine upon admission (OR
      1.98, 95%CI 1.12-3.48), acute renal failure (OR 0.11, 95%CI 0.04-0.34) and
      treatment with continuous techniques (OR 0.18, 95%CI 0.03-0.85). CONCLUSIONS:
      Mortality among critically ill patients subjected to RRT has improved in recent
      years.

PMID- 22386333
TI  - [Conservative methods for diagnosing catheter-associated bacteremia].

PMID- 22386334
TI  - [Flexible bronchoscopy in the critically ill patient. Profitability in times of
      precision].

PMID- 22386335
TI  - H1N1 influenza virus-associated encephalitis: a case report.

PMID- 22386336
TI  - [Thrombolysis in acute ischemic stroke in centers lacking a stroke unit: referral
      to reference center or on-site treatment?].
AB  - OBJECTIVE: To assess the clinical impact of on-site thrombolysis versus referral
      to another hospital in patients with ischemic stroke attended in a hospital
      lacking a stroke unit. DESIGN: Expected value decision analysis and Monte Carlo
      simulation. PATIENTS AND SETTING: Decision analysis based on a cohort study (SIT
      MOST) and a meta-analysis of randomized trials of thrombolysis versus placebo in
      patients with acute ischemic stroke. INTERVENTIONS: On-site thrombolysis (in
      hospitals lacking a stroke unit) versus delayed thrombolysis in a reference
      hospital. MAIN OUTCOMES: Neurological outcome (modified Rankin scale) three
      months after admission according to the delay in the administration of
      thrombolysis. RESULTS: At baseline (initial delay of 135 min, travel time 60
      minutes), on-site treatment was more effective than referral to another hospital
      (number of patients with favorable neurological outcome 45.3% versus 41.3%). In
      patients seen within 45 minutes of the onset of symptoms, for every 10 patients
      transferred there was an additional case with an unfavorable neurological outcome
      that could have been avoided with on-site thrombolysis. In the Monte Carlo
      analysis, biased against on-site treatment by a reduction in effectiveness of
      30%, on-site treatment was superior to patient referral in 77.2% of the cases.
      CONCLUSIONS: The available evidence does not support the recommendations of the
      national stroke strategy or some regional plans that discourage the
      administration of thrombolysis in hospitals without stroke units.

PMID- 22386337
TI  - Relevance of compartmental anatomic guidelines for biopsy of musculoskeletal
      tumors: retrospective review of 363 biopsies over a 6-year period.
AB  - PURPOSE: To retrospectively assess percutaneous core needle biopsies performed by
      radiologists and the association with tumor seeding along the biopsy tract when
      anatomic compartment guidelines are not consistently observed. MATERIALS AND
      METHODS: Retrospective data from computerized patient records and digital images
      from 363 consecutive computed tomography-guided biopsies of the lower extremity
      (thigh and leg) performed by radiologists at a single institution from August
      2002 to August 2008 were analyzed for breaches of biopsy guidelines. RESULTS: Of
      the 363 biopsies, 243 (67%) were of soft tissue lesions and 120 (33%) were of
      bony lesions. There were 188 (52%) malignant and 175 (48%) benign lesions. The
      following biopsy breaches were observed: 13 (3.6%) of anatomic compartment, 42
      (11.6%) of "vital structures," and 82 (68.3%) of needle path for bony tumors.
      Vital structures as defined by the literature included, but were not limited to,
      the following: knee joint capsule, greater trochanteric bursa, rectus femoris and
      vastus intermedius muscles, tibial tubercle, peroneus brevis and peroneus longus
      distal tendons, and neurovascular bundles. No cases of tumor recurrences could be
      attributed to needle seeding along a biopsy tract for any of these biopsy
      guideline breaches. CONCLUSIONS: The concern for needle tract seeding with
      musculoskeletal tumors is more widespread than the evidence supporting it as a
      significant or frequent complication. In this study, breaching anatomic
      compartment, vital structures (other than neurovascular structures), and
      suggested exact needle path guidelines were not associated with needle tract
      seeding in the lower extremity.

PMID- 22386338
TI  - Esophageal rupture diagnosed with bedside ultrasound.
AB  - A 69-year-old man presented to the emergency department with hematemesis,
      hypotension, tachycardia, and hypothermia. The emergency physician performed a
      bedside ultrasound of the chest, heart, and abdomen. The heart was unable to be
      visualized in the parasternal, apical, or subxiphoid windows, and free fluid and
      particulate matter were visualized in the chest and abdomen. The inability to
      visualize the heart in the normal cardiac windows suggested a diagnosis of
      pneumopericardium. Based upon the patient's presenting symptoms and ultrasound
      findings, an esophageal perforation was suspected. Esophageal perforation is a
      medical emergency. Deterioration and death due to sepsis can occur within hours
      of presentation [6]. Although there is a great deal of literature discussing the
      diagnosis of esophageal perforation by chest radiograph, computed tomography
      (CT), and esophagography, there are no articles on the role of ultrasound.
      Esophageal perforation may result in the communication of air between the
      esophagus and pericardium and the leakage of gastric contents into the chest and
      peritoneal cavity. The presence of air in the pericardial sac results in
      nonvisualization of the heart on ultrasound. Fluid in the chest and abdomen may
      be visualized in the posterior upper abdominal windows. Although these ultrasound
      findings alone are not entirely specific for esophageal perforation, when coupled
      with a high index of suspicion due to the patient presentation, ultrasound can be
      one of the most portable, readily available, low-cost, and minimally invasive
      techniques to make the diagnosis of esophageal perforation.

PMID- 22386339
TI  - Simultaneous left anterior descending and right coronary stent thrombosis after
      aspirin withdrawal.
AB  - ST-segment elevation myocardial infarction is usually caused by plaque rupture
      and subsequent thrombosis of a single culprit vessel. In rare occasions,
      simultaneous thrombosis of 2 coronary arteries occurs, which is usually
      associated with a worse prognosis. Although surgery provokes hemodynamic stress,
      leading in some instances to myocardial ischemia due to supply/demand mismatch,
      other factors may also contribute to postoperative myocardial infarction. We
      present a case of postoperative simultaneous left anterior descending and right
      coronary stent thrombosis that followed cessation of long-term aspirin therapy in
      a patient with stable coronary artery disease. This case raises concerns with
      drug-eluting stents due to the higher potential for late stent thrombosis related
      to delayed endothelialization of the stent struts. Physicians should be very
      cautious when deciding to withdraw antiplatelet therapy preoperatively to avoid
      rebound coronary thrombosis.

PMID- 22386340
TI  - Therapy-resistant ventricular tachycardia caused by amiodarone-induced
      thyrotoxicosis: a case report of electrical storm.
AB  - Electrical storm is a challenging diagnosis for the clinician and requires
      detailed evaluation of the patient. Amiodarone is frequently used for the
      cessation of ventricular tachycardia attacks. Within antiarrhythmic effects of
      amiodarone, there are some harmful effects of the recent drug. Thyroid gland
      toxicity is one of the most important adverse effects of amiodarone and is called
      amiodarone-induced thyrotoxicosis. Thyrotoxicosis may alter arrhythmia and lead
      to frequent ventricular tachycardia attacks. Herein, we report a case of
      electrical storm caused by amiodarone-induced thyrotoxicosis.

PMID- 22386341
TI  - The validity of 9 physical tests for full-thickness rotator cuff tears after
      primary anterior shoulder dislocation in ED patients.
AB  - PURPOSE: This study was undertaken to validate the diagnostic values of 9
      different physical tests in emergency department patients with primary anterior
      shoulder dislocation (PASD) to select the best screening test for full-thickness
      rotator cuff tear (FTRCT) after PASD. METHODS: A prospective analysis of 49
      consecutive patients with x-ray-confirmed PASD was performed. All patients were
      followed at an average of 6.9 days (ranged from 4 to 10 days) in the emergency
      department. On the day of follow-up, 9 physical tests (namely, Jobe test,
      external rotation lag sign test, infraspinatus muscle strength test, dropping
      test, drop test, liftoff test, internal rotation lag sign test, belly-press test,
      and belly-off test) followed by shoulder ultrasound scan were performed to detect
      FTRCT. RESULTS: The prevalence of FTRCT after PASD is 37% (95% confidence
      interval [CI], 24%-52%). Fourteen percent of the patients with PASD were
      complicated with isolated supraspinatus tendon tear, whereas 22% were complicated
      with supraspinatus tendon tear combined with subscapularis and/or infraspinatus
      tendon tear. Jobe test has the highest sensitivity among the 9 physical tests
      being evaluated. The sensitivity, specificity, positive predictive value,
      negative predictive value, likelihood ratio for positive test, and likelihood
      ratio for negative test of Jobe test as a screening test for FTRCT after PASD are
      89% (95% CI, 64%-98%), 55% (95% CI, 36%-72%), 53% (95% CI, 35%-71%), 89% (95% CI,
      65%-98%), 1.97 (95% CI, 1.29-2.99), and 0.20 (95% CI, 0.05-0.79), respectively.
      CONCLUSIONS: The prevalence of FTRCT after PASD is 37% (95% CI, 24%-52%). Jobe
      test has the highest sensitivity (89% CI, 64%-98%) among the tests.

PMID- 22386342
TI  - Seminal vesicle cysts causing pelvic pain: importance of computed tomography.
AB  - A seminal vesicle cyst is a rare etiology of pelvic pain. However, its rarity may
      result in oversight or misinterpretation if the radiologist or emergency
      physician is unfamiliar with this entity. Seminal vesicle cysts may cause pelvic
      pain because of mass effect, infection, internal hemorrhage, or urinary and
      bladder obstruction. Because seminal vesicle cysts rarely result in physical
      examination findings or laboratory abnormalities, pelvic computed tomography
      plays a pivotal role in their diagnosis and in evaluating patients with pelvic
      pain. Recognition of the imaging findings of seminal vesicle cysts is necessary
      to allow prompt, accurate diagnosis. Therefore, emergency physicians and
      radiologists interpreting examinations from the emergency department should be
      familiar with these imaging findings because seminal vesicle cysts may be the
      etiology of pelvic pain and the patient may benefit from urologic consultation
      and cyst aspiration or resection. The purposes of this article are to provide
      examples of pelvic pain caused by seminal vesicle cysts, illustrate the key
      imaging findings on computed tomography, and briefly review the literature.

PMID- 22386343
TI  - Two questions for Kounis syndrome: can we use magnetic resonance imaging in the
      diagnosis and does ST elevation correlates with troponin levels?
AB  - Kounis syndrome (KS) is an acute coronary vasospasm after exposure to an allergen
      due to mast cell degranulation and existing mediators. Various drugs, conditions,
      and environmental exposures can cause KS. We presented 2 cases, 1 of whom had
      taken an antiflu drug (containing paracetamol, pseudoephedrine, and
      dextromethorphan). His electrocardiogram (ECG) showed inferior ST elevations (2
      mm) with normal cardiac biomarkers. His cardiac magnetic resonance imaging showed
      hypokinesis and myocardial hibernation on apical septum and on the left
      ventricle. The second patient took a pill of naproxen sodium. The ECG showed 1-mm
      ST elevation in leads DII, V5, and V6. His troponin was markedly elevated. These
      cases showed that there seems to be no correlation with ECG and troponin levels
      in KS. In addition, for patients in whom KS type 1 is expected without troponin
      elevation, noninvasive cardiac magnetic resonance imaging study seems to be
      appropriate for the diagnosis of KS.

PMID- 22386344
TI  - High-velocity gunshot to the head presenting as initial minor head injury: things
      are not what they seem.
AB  - Tangential gunshots to the head are a special type of injury in which the bullet
      or bullet fragments do not penetrate the inner table of the skull. Most of
      patients experiencing this kind of injuries usually have a benign clinical
      presentation. We describe the case of a 22-year-old soldier who had a tangential
      gunshot to the head caused by a high-velocity projectile. Initially, the patient
      was neurologically intact, progressing to profound coma in the next 2 hours. The
      characteristics of the wound and initial neurologic condition led to first
      contact physicians to treat this injury as a case of mild head trauma. This case
      shows us that gunshots to the head caused by high-velocity missiles must be
      treated aggressively like a severe head injury, even when the initial neurologic
      examination is normal.

PMID- 22386345
TI  - Noninvasive Doppler ultrasound cardiac output monitor for the differential
      diagnosis of shock.

PMID- 22386346
TI  - Increased gamma-glutamyl transferase levels predict early mortality in patients
      with acute pulmonary embolism.
AB  - BACKGROUND: Increased gamma-glutamyl transferase (GGT) level is associated with
      increased oxidative stress, all-cause mortality, the development of
      cardiovascular disease, and metabolic syndrome. However, its role in acute
      pulmonary embolism (PE) is unknown. In this study, we aimed to investigate the
      relationship between GGT and early mortality in patients with acute PE. METHODS:
      A total of 127 consecutive patients with confirmed PE were evaluated. The optimal
      cutoff value of GGT to predict early mortality was measured as more than 55 IU/L
      with 94.4% sensitivity and 66.1% specificity. Patients with acute PE were
      categorized prospectively as having no increased (group I) or increased (group
      II) GGT based on a cutoff value. RESULTS: Of these 127 patients, 18 patients
      (14.2%) died during follow-up. Among these 18 patients, 1 (1.4%) patient was in
      group I, and 17 (30.9%) patients were in group II (P < .001). gamma-Glutamyl
      transferase level on admission, presence of shock, heart rate, oxygen saturation,
      right ventricular dilatation/hypokinesia, main pulmonary artery involvement,
      troponin I, alanine aminotransferase, alkaline phosphatase, and creatinine levels
      were found to have prognostic significance in univariate analysis. In the
      multivariate Cox proportional hazards model, GGT level on admission (hazard ratio
      [HR], 1.015; P = .017), presence of shock (HR, 15.124; P = .005), age (HR, 1.107;
      P = .010), and heart rate (HR, 1.101; P = .032) remained associated with an
      increased risk of acute PE-related early mortality after the adjustment of other
      potential confounders. CONCLUSIONS: We have shown that a high GGT level is
      associated with worse hemodynamic parameters, and it seems that GGT helps risk
      stratification in patients with acute PE.

PMID- 22386347
TI  - Status epilepticus after myelography with iohexol (Omnipaque).
AB  - Myelography has been of great use as a diagnostic modality, especially when other
      modalities were not conclusive.However, considering the invasive nature of
      myelography, it should receive the attention of medical personnel for them to be
      aware of its possible complications, especially when newer agents are applied as
      the contrast media. Myelography could lead to some common adverse effects and
      complications, but in this case report, we will present one of the most serious
      and uncommon complications accompanied with myelography using Omnipaque, a
      nonionic second-generation contrast agent. These complications include lower
      extremity myoclonic spasms, tonic seizure leading to status epilepticus,
      rhabdomyolysis, disseminated intravascular coagulation and anaphylactic shock.
      Having the knowledge of possible complications and available solutions,
      particularly fatal ones, could prepare medical staff beforehand for primary and
      secondary preventions.

PMID- 22386348
TI  - Epinephrine, vasopressin, and nitroglycerin improve neurologic outcome in porcine
      asphyxial cardiac arrest.
AB  - AIM: The aim of the present study was to assess whether the combination of
      epinephrine, vasopressin, and nitroglycerin would improve initial resuscitation
      success, 24-hour survival, and neurologic outcome compared with epinephrine alone
      in a swine model of asphyxial cardiac arrest (CA). MATERIALS AND METHODS: This
      prospective randomized experimental study was conducted at a laboratory research
      department. Twenty male Landrace/Large-White pigs 12 to 15 weeks of age were
      investigated. Asphyxial CA was induced by occlusion of the endotracheal tube.
      Pigs remained untreated for 4 minutes before attempting resuscitation by
      unclamping the endotracheal tube, mechanical ventilation, chest compressions, and
      epinephrine (group E) or a combination of epinephrine with vasopressin and
      nitroglycerin (group EVN) administered intravenously. In case of restoration of
      spontaneous circulation, the animals were supported for 30 minutes and then
      observed for 24 hours. RESULTS: Coronary perfusion pressure and mean arterial
      pressure were significantly increased during cardiopulmonary resuscitation in
      group EVN. In both groups, restoration of spontaneous circulation and survival
      rates were comparable (P value, nonsignificant). At 24 hours after CA, neurologic
      deficit score was significantly better in animals treated with the combination
      pharmacotherapy (P < .001). Brain histologic damage score was also higher in
      group EVN compared with group E (P < .001). Total histologic damage score and
      neurologic deficit score showed a statistical significant correlation (P < .001).
      CONCLUSION: In this porcine model of asphyxial CA, the addition of nitroglycerin
      to vasopressin and epinephrine maintained elevated coronary perfusion pressure
      during asphyxia CA and resulted in significantly better neurologic and
      histopathologic outcome in comparison with epinephrine alone.

PMID- 22386349
TI  - The role of multidetector-row computed tomography in diagnosis of left atrial
      aneurysm.

PMID- 22386350
TI  - Comment on "a novel approach to confirming nasogastric tube placement in the ED".

PMID- 22386351
TI  - National representation in the emergency medicine literature: a bibliometric
      analysis of highly cited journals.
AB  - OBJECTIVE: In recent years, significant growth has been seen in the field of
      emergency medicine. However, the national productivity to the field of emergency
      medicine remains unknown. This study aimed to reveal the national contributions
      in the field of emergency medicine. METHODS: Articles published in 13 highly
      cited journals in emergency medicine in 2006 to 2010 were retrieved from PubMed
      and Science Citation Index. The number of total articles, the per-capita numbers,
      impact factors (IFs), and citations were tabulated to assess the contribution of
      different countries. RESULTS: A total number of 9775 articles were published in
      the 13 journals from 2006 to 2010 worldwide. West Europe, North America, and East
      Asia were the most productive regions. High-income countries published 87.9% of
      the total articles. United States published the most number of articles in 2006
      to 2010 (4523/9775, or 46.3%), followed by United Kingdom, Australia, China, and
      Canada. Besides, United States also had the highest total IFs (8729.73) and total
      citations (22,117). When normalized to population size, Australia had the highest
      number of articles per million persons (26.00). Germany had the highest mean IF
      (2.27) and mean citations (6.87). CONCLUSIONS: United States is the most
      productive country in the field of emergency medicine.

PMID- 22386352
TI  - Inequalities in the early treatment of women and men with acute chest pain?
AB  - PURPOSE: The aim of this study was to identify sex differences in the early chain
      of care for patients with chest pain. DESIGN: This is a retrospective study
      performed at 3 centers including all patients admitted to the emergency
      department because of chest pain, during a 3-month period in 2008, in the
      municipality of Goteborg. Chest pain or discomfort in the chest was the only
      inclusion criterion. There were no exclusion criteria. DATA SOURCES: Data were
      retrospectively collected from ambulance and medical records and
      electrocardiogram (ECG), echocardiography, and laboratory databases. MAIN
      FINDINGS: A total of 2588 visits (1248 women and 1340 men) made by 2393 patients
      were included. When adjusting for baseline variables, female sex was
      significantly associated with a prolonged delay time (defined as above median)
      between (a) admission to hospital and admission to a hospital ward (odds ratio
      [OR], 1.59; 95% confidence interval [CI], 1.25-2.03), (b) first physical contact
      and first dose of aspirin (OR, 2.22; 95% CI, 1.30-3.82), and (c) admission to
      hospital and coronary angiography (OR, 2.50; 95% CI, 1.29-5.13). Delay time to
      the first ECG recording did not differ significantly between women and men.
      PRINCIPAL CONCLUSIONS: Among patients hospitalized due to chest pain, when
      adjusting for differences at baseline, female sex was associated with a prolonged
      delay time until admission to a hospital ward, to administration of aspirin, and
      to performing a coronary angiography. There was no difference in delay to the
      first ECG recording.

PMID- 22386353
TI  - Neurologic complaints in young children in the ED: when is cranial computed
      tomography helpful?
AB  - MAIN OBJECTIVE: The objective of this study is to describe the use of emergent
      head computed tomography (CT) in young children and ask in which circumstances
      scans contributed to immediate management. METHODS: We reviewed electronic
      records of children, aged 1 month through 6 years, who received a head CT at a
      large suburban emergency department between February 2008 and February 2009. Age,
      sex, chief complaint, history, physical examination, indication for and results
      of head CT, red flags in history or physical examination, final disposition, and
      number of head CT scans performed to date were recorded. Abnormalities on CT
      scans were classified as significant or incidental, and subsequent interventions
      were documented. RESULTS: Emergent head CTs were performed on 394 children. The
      most common indications were trauma, 65%; seizure, 11%; and headache, 6%.
      Computed tomographic abnormalities were found in 40% (154 children): 32
      significant findings,104 incidental findings, and 22 preexisting abnormalities.
      Four children with significant findings required immediate intervention. They all
      had red flags in both history and physical examination, and 3 of 4 children had
      known preexisting pathology; 1 child had nonaccidental trauma. Only 1 child had a
      significantly abnormal CT with no identifiable red flags; this child was admitted
      for observation and was discharged within 24 hours. Approximately a third of
      children had no readily identifiable red flag for the CT scans that they
      received. Of note, 20% of the young children had received more than 1 head CT
      scan to date, and 6% had between 6 and 20 scans. CONCLUSIONS: Every child in this
      sample who required emergency intervention had red flags on history and physical
      examination. The 35% of CT scans performed in young children without red flags
      did not contribute usefully to their acute management.

PMID- 22386354
TI  - Unusual cause of neck pain: septic arthritis of a cervical facet.
AB  - Neck pain is a common cause for presentation to an emergency department. Most
      causes are benign and often secondary to arthritis or injuries. We present a case
      of septic cervical facet arthritis, a very rare cause of neck pain. The clinical
      presentation of septic cervical facet arthritis includes fever, neck pain that is
      often unilateral that is worse with movement, nerve root symptoms, and radiation
      of pain to the shoulder. Consequences may be severe and include joint destruction
      and infection progression. Symptoms may be indolent, and a high index of
      suspicion is necessary to make this diagnosis.

PMID- 22386355
TI  - ED crowding and the use of nontraditional beds.
AB  - BACKGROUND AND OBJECTIVES: In an effort to compensate for crowding, many
      emergency departments (EDs) evaluate and treat patients in nontraditional
      settings such as gurneys in hallways and conference rooms. The impact of this
      practice on ED evaluation time is unknown. RESEARCH DESIGN AND SUBJECTS: A
      historical cohort of adult ED visits to an academic hospital between August 1,
      2009 and August 1, 2010, was used to evaluate the relationship between ED bed
      assignment (traditional, hallway, or conference room bed) and mean ED evaluation
      time, defined as the time spent in an ED bed before admission or discharge. Chief
      complaints were categorized into the 5 most frequent categories:
      abdominal/genitourinary, joint/muscle, general (fever, malaise), head/neck, and
      other. Multiple linear regression and marginal prediction were used to calculate
      the mean ED evaluation times for each bed type, overall, and by chief complaint
      category. RESULTS: During the study period, 15 073 patient visits met the
      inclusion criteria. After adjustment for patient and ED factors, assignments to
      hallway and conference room beds were associated with increases in a mean ED
      evaluation time of 13.3 minutes (95% confidence interval, 13.2-13.3) and 10.9
      minutes (95% confidence interval, 10.8-10.9), respectively, compared with the
      traditional bed ED evaluation time. This varied by chief complaint category.
      CONCLUSIONS: Use of nontraditional beds is associated with increases in mean ED
      evaluation time; however, these increases are small and may be further minimized
      by restricting the use of nontraditional beds to patients with specific chief
      complaints. Nontraditional beds may have a role in improving ED throughput during
      times of crowding.

PMID- 22386356
TI  - Successful treatment of thyroid crisis accompanied by hypoglycemia, lactic
      acidosis, and multiple organ failure.
AB  - We describe a case of thyroid crisis with hypoglycemia, lactic acidosis, multiple
      organ failure, and disseminated intravascular coagulation--rare but severe
      complications of thyroid crisis. The patient was a 59-year-old Chinese woman who
      presented with evidence of heart failure and atrial fibrillation. Analysis of a
      blood sample yielded astonishing results: her blood glucose was 1.7 mmol/L, and
      lactate greater than 15 mmol/L with the arterial pH as 6.94. Liver enzymes
      (alanine aminotransferase, 1846 U/L; aspartate aminotransferase, 6242 U/L) and
      bilirubin elevated rapidly and dramatically. Prompt treatments such as mechanical
      ventilation, plasma exchange, and continuous venovenous hemofiltration were
      preformed, along with antithyroid medication. The patient finally survived after
      3 weeks of intensive care. We herein discuss the possible mechanisms of these
      metabolic disorders in thyroid crisis and possible therapeutic measures that
      could be used to reduce mortality.

PMID- 22386357
TI  - Anaphylactic shock due to kiwifruit.
AB  - A 44-year-old male patient was admitted to our emergency department (ED) with an
      episode of severe anaphylaxis displaying generalized urticaria and dyspnea 1 hour
      after consuming a kiwifruit. Initially, the patient reported discrete itching of
      his abdominal skin and was in moderate respiratory distress. The patient's wheal
      response and itch were attenuated 30 minutes after emergency treatment with
      intravenous antianaphylaxis drugs. However, he had symptoms of the chest
      distress, dizzy, and dysphoria. His vital signs exacerbated. After sufficient
      antianaphylaxis treatment, the patient's anaphylaxis shock symptoms had not been
      significantly improved. We reviewed the history. The patient had eaten a full
      fresh kiwifruit, so there may be some kiwifruit pulp left in the patient's
      stomach. After self-induced vomiting, the patient's clinical condition gradually
      improved without any changes in dosage of dopamine. After another 10 hours of
      observation and preventive therapy training, the patient was discharged. Cases of
      patients with anaphylactic reaction to kiwifruit and dragon fruit have not been
      reported yet. In the ED, it is easy to overlook the prolonged exposure to
      allergen in patients with oral allergy syndrome. If the patient has consumed much
      food or drugs to cause the allergic reaction, self-induced vomiting or gastric
      lavage to clean allergen may be useful.

PMID- 22386358
TI  - Effect of advanced age and vital signs on admission from an ED observation unit.
AB  - OBJECTIVES: The primary objective was to determine the relationship between
      advanced age and need for admission from an emergency department (ED) observation
      unit. The secondary objective was to determine the relationship between initial
      ED vital signs and admission. METHODS: We conducted a prospective, observational
      cohort study of ED patients placed in an ED-based observation unit. Multivariable
      penalized maximum likelihood logistic regression was used to identify independent
      predictors of need for hospital admission. Age was examined continuously and at a
      cutoff of 65 years or more. Vital signs were examined continuously and at
      commonly accepted cutoffs.We additionally controlled for demographics, comorbid
      conditions, laboratory values, and observation protocol. RESULTS: Three hundred
      patients were enrolled, 12% (n = 35) were 65 years or older, and 11% (n = 33)
      required admission. Admission rates were 2.9% (95% confidence interval [CI],
      0.07%-14.9%) in older adults and 12.1% (95% CI, 8.4%-16.6%) in younger adults. In
      multivariable analysis, age was not associated with admission (odds ratio [OR],
      0.30; 95% CI, 0.05-1.67). Predictors of admission included systolic pressure 180
      mm Hg or greater (OR, 4.19; 95% CI, 1.08-16.30), log Charlson comorbidity score
      (OR, 2.93; 95% CI, 1.57-5.46), and white blood cell count 14,000/mm(3) or greater
      (OR, 11.35; 95% CI, 3.42-37.72). CONCLUSIONS: Among patients placed in an ED
      observation unit, age 65 years or more is not associated with need for admission.
      Older adults can successfully be discharged from these units. Systolic pressure
      180 mm Hg or greater was the only predictive vital sign. In determining
      appropriateness of patients selected for an ED observation unit, advanced age
      should not be an automatic disqualifying criterion.

PMID- 22386359
TI  - The difference in myocardial injuries and mitochondrial damages between asphyxial
      and ventricular fibrillation cardiac arrests.
AB  - INTRODUCTION: Ventricular fibrillation (VF) and asphyxia account for most cardiac
      arrests but differ in cardiac arrest course, neurologic deficit, and myocardial
      damage. In VF resuscitation, cardiac mitochondria were known to be damaged via
      excess generation of reactive oxygen species. This study evaluated the difference
      of cardiac mitochondrial damages between VF and asphyxial cardiac arrests.
      METHODS: In the VF + electrical shock (ES) group, VF was induced and untreated
      for 5 minutes, followed by 1 minute of cardiopulmonary resuscitation (CPR) and 1
      ES of 5 J. Animals were killed immediately after ES. In the asphyxia group,
      cardiac arrest was induced by airway obstruction, and then pulselessness was
      maintained for 5 minutes, followed by 1 minute of CPR. The animals were killed
      immediately after CPR. The histology and ultrastructural changes of myocardium
      and complex activities and respiration of mitochondria were evaluated. The
      mitochondrial permeability transition pore opening was measured based on
      mitochondrial swelling rate. RESULTS: The histopathologic examinations showed
      myocardial necrosis and mitochondrial damage in both cardiac arrests. Instead of
      regional damages of myocardium in the VF + ES group, the myocardial injury in the
      asphyxia group distributed diffusely. The asphyxia group demonstrated more severe
      mitochondrial damage than the VF + ES group, which had a faster mitochondrial
      swelling rate, more decreased cytochrome c oxidase activity, and more impaired
      respiration. CONCLUSIONS: Both VF and asphyxial cardiac arrests caused myocardial
      injuries and mitochondrial damages. Asphyxial cardiac arrest presented more
      diffuse myocardial injuries and more severe mitochondrial damages than VF cardiac
      arrest.

PMID- 22386360
TI  - Pediatric flecainide toxicity from a double dose.
AB  - A 23-month-old boy was brought to the emergency department of an adult and
      pediatric tertiary care center 1 hour after an inadvertent "double dose" of 120
      mg flecainide (9.2 mg/kg). His electrocardiogram revealed sinus rhythm with a
      terminal R wave in aVR greater than 7 mm, a bifascicular block, and prolonged QRS
      and QTc intervals. A dramatic improvement in the bifascicular block and terminal
      R wave occurred after the administration of sodium bicarbonate. He was discharged
      after 36 hours with no complications. This case demonstrates that flecainide can
      cause significant cardiac conduction disturbances in doses much lower than
      previously described. All supratherapeutic ingestions should be assessed in
      hospital.

PMID- 22386361
TI  - Bedside ultrasound of acute adrenal hemorrhage.
AB  - Most complications from traumatic isolated adrenal hemorrhage are thought to be
      minor and do not require specific treatment. However, there are often additional
      intraabdominal organ injuries, such as liver and ipsilateral kidney, associated
      with adrenal injury. It is, therefore, important to identify these injuries as
      early as possible, preferably on initial assessment. We describe a case of a 43
      year-old man who presented to the emergency department after sustaining blunt
      force trauma to the flank during a soccer match and was subsequently diagnosed
      with acute adrenal injury by use of bedside ultrasonography.

PMID- 22386362
TI  - Plasma persistence of 2-aminothiazoline-4-carboxylic acid in rat system
      determined by liquid chromatography tandem mass spectrometry.
AB  - 2-Aminothiazoline-4-carboxylic acid (ATCA) was intravenously injected to rats in
      order to investigate its plasma distribution. ATCA was extracted from plasma
      samples by solid phase extraction (SPE) and molecularly imprinted polymer stir
      bar sorption extraction (MIP-SBSE). Detection and quantification of ATCA were
      achieved by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). It
      was found that the intravenously injected ATCA concentration quickly decreased to
      half within 2.5h in the rat system. However, after 2.5 h, the concentration of
      ATCA in plasma stayed constant at least 5 folds above the endogenous ATCA level
      for more then 48 h. This finding can be used for evaluating ATCA's diagnostic and
      forensic value as a biomarker for cyanide exposure.

PMID- 22386363
TI  - Recovery of active anti TNF-alpha ScFv through matrix-assisted refolding of
      bacterial inclusion bodies using CIM monolithic support.
AB  - Anti TNF-alpha molecules are important as therapeutic agents for many of the
      autoimmune diseases in chronic stage. Here we report the expression and
      purification of a recombinant single chain variable fragment (ScFv) specific to
      TNF-alpha from inclusion bodies. In contrast to the conventional on column
      refolding using the soft gel supports, an efficient methodology using monolithic
      matrix has been employed. Nickel (II) coupled to convective interaction media
      (CIM) support was utilized for this purpose with 6M guanidine hydrochloride
      (GuHCl) as the chaotropic agent. The protein purified after solubilization and
      refolding proved to be biologically active with an IC50 value of 15 MUg. To the
      best of our knowledge, this is the first report showing the application of
      methacrylate based chromatographic supports for matrix-assisted refolding and
      purification of Escherichia coli inclusion bodies. The results are promising to
      elaborate the methodology further to exploit the potential positive features of
      monoliths in protein refolding science.

PMID- 22386364
TI  - Livestock-associated Staphylococcus aureus: origin, evolution and public health
      threat.
AB  - Staphylococcus aureus is a major pathogen responsible for severe nosocomial and
      community-associated infections of humans and infections of economically
      important livestock species. In recent years, studies into livestock-associated
      S. aureus including methicillin-resistant (MRSA) strains have provided new
      information regarding their origin and host adaptation, and their capacity to
      cause zoonotic infections of humans. Furthermore, a potential role for human
      activities such as domestication and industrialisation in the emergence of S.
      aureus clones affecting livestock has been highlighted. Here, I summarise recent
      developments in this emerging field and suggest questions of importance for
      future research efforts.

PMID- 22386365
TI  - Effect of butyrate on aromatase cytochrome P450 levels in HT29, DLD-1 and LoVo
      colon cancer cells.
AB  - Epidemiological studies suggest that colonic production of butyrate and estrogen
      may be involved in human susceptibility to colorectal cancer (CRC). Estrone (E1)
      can be produced by the aromatase pathway during the conversion of androstenedione
      (A) to E1. Therefore, we studied the effect of sodium butyrate (NaBu) on the
      CYP19A1 transcript and protein levels and on the conversion of A to E1 in HT29,
      DLD-1 and LoVo CRC cells. We found that NaBu significantly downregulated CYP19A1
      transcript and protein levels, a phenomenon that was associated with reduced
      conversion of A to E1 in HT29, DLD-1 and LoVo cells. Our studies demonstrated
      that, although butyrate exhibited a protective role in CRC development, this
      compound may reduce aromatase activity and the production of E1 in colon cancer
      cells.

PMID- 22386366
TI  - Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine
      model of cardiomyopathy.
AB  - Doxorubicin (DXR) is one of the most effective antineoplastic agents. However,
      the optimal clinical use of this agent is limited because of marked
      cardiomyopathy and congestive heart failure. Renin angiotensin system (RAS) plays
      an important role in the development of cardiac hypertrophy, reperfusion injury
      and congestive heart failure. Aliskiren (ALK) is a direct inhibitor of renin and
      does not affect other systems involved in cardiovascular regulation. This study
      was designed to explore the possible protective effects of ALK (30 and 100 mg/kg,
      per oral [p.o.] respectively for 42 days) in chronic model of DXR (1.25 mg/kg,
      intraperitoneally (i.p.) sixteen equal cumulative doses) induced cardiomyopathy
      in rats. DXR treatment significantly (P<0.01) increased the activities of serum
      creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiomyocyte caspase-3 and
      catalase (CAT). ALK (100 mg/kg) treatment prevented the animals significantly
      (P<0.01) from rise in the above indices. Furthermore ALK (100 mg/kg)
      significantly restores the DXR-induced decrease in antioxidant defense, reduced
      glutathione (GSH) and superoxide dismutase (SOD). Transmission electron
      microscopic studies showed that DXR caused apoptosis in myocardium, manifested as
      condensation of chromatin network at the margins and rupture of nuclear membrane
      which was well protected by ALK (100 mg/kg) treatment. The present study
      indicates that ALK protected rats from DXR-induced cardiomyopathy.

PMID- 22386367
TI  - Regulation of CD44 expression by tumor necrosis factor-alpha and its potential
      role in breast cancer cell migration.
AB  - CD44 molecule plays critical role in distant malignant metastasis. It is
      expressed in standard form (CD44s) or variant form (CD44v). Tumor necrosis factor
      alpha (TNF-alpha) is highly expressed in the cancer microenvironment. TNF-alpha
      was reported to modulate CD44 expression in several kinds of cancer. However,
      little is known about pathological role of TNF-alpha in breast cancer (BC) cells.
      In the current investigation, we investigated the effect of TNF-alpha on BC cells
      (MCF-7 and MDA-MB-231) viability, CD44 expression, and in vitro migration. We
      found that TNF-alpha down-regulated CD44s expression, up-regulated CD44v3 and
      CD44v6 expression through JNK pathway in MCF-7 cells. In MDA-MB-231 cells, TNF
      alpha up-regulated CD44s, CD44v3 and CD44v6 expression via p38 pathway. These
      data indicate important role of CD44 molecule in BC pathology.

PMID- 22386368
TI  - Synthesis and cytotoxicity evaluation of biaryl-based chalcones and their
      potential in TNFalpha-induced nuclear factor-kappaB activation inhibition.
AB  - A series of biaryl-based chalcones were designed as a combination of the natural
      chalcone and biphenyl moieties, and synthesized by two step chemistry involving
      Knoevenagel reaction and microwave assistant Suzuki coupling. Sulforhodamine B
      (SRB) assay was performed to evaluate the cell viability inhibitory abilities of
      these compounds against five cancer cell lines (A549, CNE2, SW480, MCF-7, and
      HepG2) from different tissues. Their Nuclear Factor-kappaB (NF-kappaB) nuclear
      translocation inhibitory activities were further investigated by High Content
      Analysis (HCA) based assay. Most of the compounds showed moderate to strong
      anticancer and NF-kappaB nuclear translocation inhibition activities and potent
      compounds were found.

PMID- 22386369
TI  - Vorinostat: a potent agent to prevent and treat laser-induced corneal haze.
AB  - PURPOSE: This study investigated the efficacy and safety of vorinostat, a
      deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze
      following photorefractive keratectomy (PRK) in rabbits in vivo and transforming
      growth factor beta 1 (TGFbeta1) -induced corneal fibrosis in vitro. METHODS:
      Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in
      cultured human and rabbit corneal fibroblasts was activated with TGFbeta1.
      Vorinostat (25 MUm) was topically applied once for 5 minutes on rabbit cornea
      immediately after PRK for in vivo studies. Vorinostat (0 to 25 MUm) was given to
      human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies.
      Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined
      vorinostat toxicity, whereas real-time polymerase chain reaction,
      immunocytochemistry, and immunoblotting were used to measure its efficacy.
      RESULTS: Single 5-minute vorinostat (25 MUm) topical application on the cornea
      following PRK significantly reduced corneal haze (P<.008) and fibrotic marker
      proteins (alpha-smooth muscle actin and f-actin; P<.001) without showing redness,
      swelling, or inflammation in rabbit eyes in vivo screened 4 weeks after PRK.
      Vorinostat reduced TGFbeta1-induced fibrosis in human and rabbit corneas in vitro
      in a dose-dependent manner without altering cellular viability, phenotype, or
      proliferation. CONCLUSIONS: Vorinostat is non-cytotoxic and safe for the eye and
      has potential to prevent laser-induced corneal haze in patients undergoing PRK
      for high myopia.

PMID- 22386370
TI  - Comparative evaluation of suture-assisted and fibrin glue-assisted scleral
      fixated intraocular lens implantation.
AB  - PURPOSE: To compare the visual outcomes and complications after suture-assisted
      and fibrin glue-assisted scleral fixated intraocular (IOL) implantation. METHODS:
      Scleral fixated IOL implantation was performed in patients with inadequate
      capsular support. Intraocular lens fixation was achieved using sutures or fibrin
      glue. Main parameters evaluated were visual outcomes and complications. RESULTS:
      Fifty patients were included in the study (n=25 suture, n=25 glue). The most
      common indication for scleral fixated IOL implantation was cataract surgery
      complicated with posterior capsule rupture (29/50 [58%]). No significant
      differences were noted between demographic characteristics, surgical indications,
      and preoperative corrected distance visual acuity (CDVA) in either group
      (P=.680). No intraoperative complications related to IOL fixation were
      encountered in any case. At last follow-up (6 months), CDVA was 20/40 or better
      in 88% and 84% of patients in the suture and glue groups, respectively.
      Postoperative inflammation (48% vs 16%) and glaucoma (40% vs 16%) were seen more
      frequently in eyes with sutures as compared to eyes with glue. Overall, a
      significantly higher number of complications were encountered in eyes with suture
      fixation (14/25 [56%]) compared to eyes with glue fixation (7/25 [28%]) (P=.045).
      CONCLUSIONS: Although visual outcomes were similar at the end of 6 months in eyes
      that underwent suture- and glue-assisted scleral fixated IOL implantation, fibrin
      glue was associated with fewer complications.

PMID- 22386371
TI  - Scheimpflug camera measurement of anterior and posterior corneal curvature in
      eyes with previous radial keratotomy.
AB  - PURPOSE: To compare the anterior and posterior corneal curvature in eyes with
      previous radial keratotomy (RK) to normal unoperated eyes. METHODS: In this
      retrospective observational case series, 29 eyes from 29 consecutive patients
      were analyzed and compared to a control group of 71 unoperated eyes. Corneal
      imaging was obtained by a rotating Scheimpflug camera (Pentacam, Oculus
      Optikgerate GmbH). Anterior and posterior corneal curvature radii were measured
      at the 3-mm zone. RESULTS: The mean anterior and posterior corneal radii were
      9.54 +/- 0.89 and 8.54 +/- 1.01 mm, respectively, both values being significantly
      higher than in the control group (7.81 +/- 0.28 and 6.40 +/- 0.24 mm,
      respectively, P<.0001). The mean anterior-to-posterior corneal curvature ratio
      was 1.12 +/- 0.07, a value significantly lower than in the control group (1.22 +/
      0.03, P<.0001). Mean corneal flattening was more evident in the posterior
      (33.44%) than in the anterior (22.15%) corneal curvature. The mean keratometric
      index, as calculated with the Gullstrand equation for thick lenses, was 1.3319 +/
      0.0026, a value significantly higher than in the control group (1.3281 +/-
      0.0011, P<.0001). Linear regression detected a significant and directly
      proportional relationship between the number of radial incisions and flattening
      of both corneal surfaces (P<.0001). CONCLUSIONS: After RK, both corneal surfaces
      flatten but do not deform in parallel as commonly accepted, as shown by the fact
      that the anterior-to-posterior corneal curvature ratio decreases. This finding
      invalidates the standard keratometric index and thus has relevant implications
      for intraocular lens power calculation in RK eyes.

PMID- 22386372
TI  - AcrySof cachet phakic intraocular lens in myopic patients: visual performance,
      wavefront error, and lens position.
AB  - PURPOSE: To evaluate visual and aberrometric outcomes and position of the AcrySof
      Cachet (Alcon Laboratories Inc) angle-supported phakic intraocular lens (PIOL)
      for correction of myopia in adults. METHODS: This prospective study included 36
      consecutive eyes with moderate to high myopia in which an AcrySof Cachet PIOL was
      implanted to minimize refractive error. Follow-up was up to 1 year. RESULTS: Mean
      manifest spherical equivalent refraction reduced significantly from -14.90 +/-
      0.90 diopters (D) to -0.29 +/- 0.30 D at 1 month and remained stable at 1 year
      (P<.001). Mean uncorrected distance visual acuity was >0.1 logMAR (20/20 Snellen)
      in 56% of patients and >0.3 logMAR (20/25 Snellen) in 100% of patients. Corrected
      distance visual acuity was >0.1 logMAR (20/20 Snellen) in 78% of patients and
      >0.3 logMAR (20/25 Snellen) in 100% of patients. Mean endothelium-PIOL distance
      and mean PIOL-crystalline distance were within recommended values at all
      postoperative evaluations. Statistically significant variations for these
      variables were not observed. Anterior chamber depth, safety center distance, and
      vault center distance showed significant reduction after accommodation (P<.01).
      Anterior chamber depth and safety center distance significantly increased after
      pupil dilation (P<.01). Mean percentage of endothelial cell loss was 4.04% at 1
      year. The root-mean-square of total higher order aberrations and spherical, coma,
      and trefoil aberrations did not change significantly from pre- to
      postoperatively. CONCLUSIONS: The AcrySof Cachet PIOL was effective in the
      correction of moderate to high myopia and provided excellent visual performance
      with no modification of physiologic ocular wavefront error. Adequate distance
      from the cornea and crystalline lens was maintained with no significant change
      during follow-up and under different environmental conditions.

PMID- 22386373
TI  - Effective dose reduction to cardiac structures using protons compared with 3DCRT
      and IMRT in mediastinal Hodgkin lymphoma.
AB  - PURPOSE: We investigated the dosimetric impact of proton therapy (PT) on various
      cardiac subunits in patients with Hodgkin lymphoma (HL). METHODS AND MATERIALS:
      From June 2009 through December 2010, 13 patients were enrolled on an
      institutional review board-approved protocol for consolidative involved-node
      radiotherapy (INRT) for HL. Three separate treatment plans were developed
      prospectively by using three-dimensional conformal radiotherapy (3DCRT),
      intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were
      retrospectively contoured on the 11 patients with intravenous-contrast simulation
      scans, and the doses were calculated for all treatment plans. A Wilcoxon paired
      test was performed to evaluate the statistical significance (p < 0.05) of 3DCRT
      and IMRT compared with PT. RESULTS: The mean heart doses were 21 Gy, 12 Gy, and 8
      Gy (relative biologic effectiveness [RBE]) with 3DCRT, IMRT, and PT,
      respectively. Compared with 3DCRT and IMRT, PT reduced the mean doses to the left
      and right atria; the left and right ventricles; the aortic, mitral, and tricuspid
      valves; and the left anterior descending, left circumflex, and right circumflex
      coronary arteries. CONCLUSIONS: Compared with 3DCRT and IMRT, PT reduced the
      radiation doses to all major cardiac subunits. Limiting the doses to these
      structures should translate into lower rates of cardiac toxicities.

PMID- 22386374
TI  - Onset time of tumor repopulation for cervical cancer: first evidence from
      clinical data.
AB  - PURPOSE: Accelerated tumor repopulation has significant implications in low-dose
      rate (LDR) brachytherapy. Repopulation onset time remains undetermined for
      cervical cancer. The purpose of this study was to determine the onset time of
      accelerated repopulation in cervical cancer, using clinical data. METHODS AND
      MATERIALS: The linear quadratic (LQ) model extended for tumor repopulation was
      used to analyze clinical data and magnetic resonance imaging-based three
      dimensional tumor volumetric regression data from 80 cervical cancer patients who
      received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose
      was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the
      total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups
      according to total dose and treatment time. The tumor control probability (TCP)
      was calculated for each group. The least chi(2) method was used to fit the TCP
      data with two free parameters: onset time (T(k)) of accelerated repopulation and
      number of clonogens (K), while other LQ model parameters were adopted from the
      literature, due to the limited patient data. RESULTS: Among the 11 patient
      groups, TCP varied from 33% to 100% as a function of radiation dose and overall
      treatment time. Higher dose and shorter treatment duration were associated with
      higher TCP. Using the LQ model, we achieved the best fit with onset time T(k) of
      19 days and K of 139, with uncertainty ranges of (11, 22) days for T(k) and (48,
      1822) for K, respectively. CONCLUSION: This is the first report of accelerated
      repopulation onset time in cervical cancer, derived directly from clinical data
      by using the LQ model. Our study verifies the fact that accelerated repopulation
      does exist in cervical cancer and has a relatively short onset time. Dose
      escalation may be required to compensate for the effects of tumor repopulation if
      the radiation therapy course is protracted.

PMID- 22386375
TI  - Locoregional failure in early-stage breast cancer patients treated with radical
      mastectomy and adjuvant systemic therapy: which patients benefit from
      postmastectomy irradiation?
AB  - PURPOSE: To assess the locoregional failure in patients with Stage I-II breast
      cancer treated with radical mastectomy and to evaluate whether a subset of these
      patients might be at sufficiently high risk of locoregional recurrence (LRR) to
      benefit from postmastectomy irradiation (PMRT). METHODS AND MATERIALS: Stage I-II
      breast cancer patients (n = 150) treated with radical mastectomy without adjuvant
      irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported.
      Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional
      hazards methods were used to evaluate potential risk factors. RESULTS: Median
      follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three
      (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy
      alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal
      therapy. Statistically significant factors associated with increased risk of LRR
      were premenopausal status (p = 0.004), estrogen receptor negative cancer (p =
      0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T
      and N stage were not associated with increased risk of regional recurrence. The 5
      year LRR rate for patients with zero or one, two, three, and four risk factors
      was 1%, 10.3%, 24.2%, and 75%, respectively. CONCLUSIONS: A subset of patients
      with early-stage breast cancer is at high risk of LRR, and therefore PMRT might
      be beneficial.

PMID- 22386376
TI  - Volumetric modulation arc radiotherapy with flattening filter-free beams compared
      with static gantry IMRT and 3D conformal radiotherapy for advanced esophageal
      cancer: a feasibility study.
AB  - PURPOSE: A feasibility study was performed to evaluate RapidArc (RA), and the
      potential benefit of flattening filter-free beams, on advanced esophageal cancer
      against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal
      radiotherapy (3D-CRT). METHODS AND MATERIALS: The plans for 3D-CRT and IMRT with
      three to seven and five to seven fixed beams were compared against double
      modulated arcs with avoidance sectors to spare the lungs for 10 patients. All
      plans were optimized for 6-MV photon beams. The RA plans were studied for
      conventional and flattening filter-free (FFF) beams. The objectives for the
      planning target volume were the volume receiving >= 95% or at most 107% of the
      prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at
      risk, the lung volume (minus the planning target volume) receiving >= 5 Gy was
      <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The
      heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The
      spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA
      were assessed to compare the normal and FFF beam characteristics. RESULTS: RA and
      IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT.
      The conformity index was 1.2 +/- 0.1 for RA and IMRT and 1.5 +/- 0.2 for 3D-CRT.
      The mean lung dose was 12.2 +/- 4.5 for IMRT, 11.3 +/- 4.6 for RA, and 10.8 +/-
      4.4 for RA with FFF beams, 18.2 +/- 8.5 for 3D-CRT. The percentage of volume
      receiving >= 20 Gy ranged from 23.6% +/- 9.1% to 21.1% +/- 9.7% for IMRT and RA
      (FFF beams) and 39.2% +/- 17.0% for 3D-CRT. The heart and spine objectives were
      met by all techniques. The monitor units for IMRT and RA were 457 +/- 139, 322 +/
      20, and 387 +/- 40, respectively. RA with FFF beams showed, compared with RA
      with normal beams, a ~20% increase in monitor units per Gray, a 90% increase in
      the average dose rate, and 20% reduction in beam on time (owing to different
      gantry speeds). CONCLUSION: RA demonstrated, compared with conventional IMRT, a
      similar target coverage and some better dose sparing to the organs at risk; the
      advantage against conventional 3D-CRT was more evident. RA with FFF beams
      resulted in minor improvements in plan quality but with the potential for
      additional useful reduction in the treatment time.

PMID- 22386378
TI  - Endogenous opioid release in the human brain reward system induced by acute
      amphetamine administration.
AB  - BACKGROUND: We aimed to demonstrate a pharmacologically stimulated endogenous
      opioid release in the living human brain by evaluating the effects of amphetamine
      administration on [(11)C]carfentanil binding with positron emission tomography
      (PET). METHODS: Twelve healthy male volunteers underwent [(11)C]carfentanil PET
      before and 3 hours after a single oral dose of d-amphetamine (either a "high"
      dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.25 mg total dose or
      approximately .017 mg/kg). Reductions in [(11)C]carfentanil binding from baseline
      to post-amphetamine scans (DeltaBP(ND)) after the "high" and "ultra-low"
      amphetamine doses were assessed in 10 regions of interest. RESULTS:
      [(11)C]carfentanil binding was reduced after the "high" but not the "ultra-low"
      amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior
      cingulate, and insula. CONCLUSIONS: Our findings indicate that oral amphetamine
      administration induces endogenous opioid release in different areas of human
      brain, including basal ganglia, frontal cortex areas, and thalamus. The
      combination of an amphetamine challenge and [(11)C]carfentanil PET is a practical
      and robust method to probe the opioid system in the living human brain.

PMID- 22386377
TI  - Defensive mobilization in specific phobia: fear specificity, negative
      affectivity, and diagnostic prominence.
AB  - BACKGROUND: Understanding of exaggerated responsivity in specific phobia-its
      physiology and neural mediators-has advanced considerably. However, despite
      strong phenotypic evidence that prominence of specific phobia relative to co
      occurring conditions (i.e., principal versus nonprincipal disorder) is associated
      with dramatic differences in subjective distress, there is yet no consideration
      of such comorbidity issues on objective defensive reactivity. METHODS: A
      community sample of specific phobia (n = 74 principal; n = 86 nonprincipal) and
      control (n = 76) participants imagined threatening and neutral events while
      acoustic startle probes were presented and eyeblinks (orbicularis occuli)
      recorded. Changes in heart rate, skin conductance level, and facial expressivity
      were also measured. RESULTS: Principal specific phobia patients far exceeded
      control participants in startle reflex and autonomic reactivity during
      idiographic fear imagery. Distinguishing between single and multiple phobias
      within principal phobia and comparing these with nonprincipal phobia revealed a
      continuum of decreasing defensive mobilization: single patients were strongly
      reactive, multiple patients were intermediate, and nonprincipal patients were
      attenuated-the inverse of measures of pervasive anxiety and dysphoria (i.e.,
      negative affectivity). Further, as more disorders supplanted specific phobia from
      principal disorder, overall defensive mobilization was systematically more
      impaired. CONCLUSIONS: The exaggerated responsivity characteristic of specific
      phobia is limited to those patients for whom circumscribed fear is the most
      impairing condition and coincident with little additional affective
      psychopathology. As specific phobia is superseded in severity by broad and
      chronic negative affectivity, defensive reactivity progressively diminishes.
      Focal fears may still be clinically significant but not reflected in objective
      defensive mobilization.

PMID- 22386379
TI  - Fractionation of phosphorus biowastes: characterisation and environmental risk.
AB  - Phosphorus (P) fertilizer is essential for food production and is a limiting
      factor in crop yields. However, the role of P in the eutrophication of surface
      water has long been recognised. During recent years, the input of P from
      agriculture to surface waters has increased and has been the focus for strategies
      aimed at mitigating diffuse P losses. As not all forms of P have the same
      availability, it is important to know the main forms of phosphorus in biowastes,
      and hence to develop fractionation schemes. The standards, measurements, and
      testing (SMT) procedure for phosphorus fractionation in freshwater sediments,
      developed within the framework of the Standards, Measurements, and Testing
      Program of the European Commission, was applied to 15 biowastes used frequently
      in agriculture, to obtain total P, inorganic and organic P, apatite P, and non
      apatite inorganic P. The Hedley method was applied to determine the water-soluble
      phosphorus (WSP) in all the biowastes. In addition, the aluminium, calcium, and
      iron concentrations were quantified and related to the WSP. The results confirm
      the applicability of the SMT protocol to all kinds of waste usually applied in
      agriculture. The SMT protocol revealed the existence of large amounts of
      inorganic P and non-apatite inorganic P, the most-available forms of P for all
      the biowastes. The comparison of the data for total P (SMT protocol) and WSP
      (Huang protocol) does not show a good linear relationship between these
      parameters. Instead, the relationship between [aluminium+calcium+iron] and WSP is
      a better indication of the availability of P.

PMID- 22386381
TI  - Utility of plasma matrix metalloproteinase-9 as a possible diagnostic marker of
      endoleak post endovascular aneurysm repair.

PMID- 22386382
TI  - Laparoscopic versus open approach for aortobifemoral bypass for severe aorto
      iliac occlusive disease--a multicentre randomised controlled trial.
AB  - OBJECTIVES: To investigate differences between open and laparoscopic
      aortobifemoral bypass surgery for aorto-iliac occlusive disease on postoperative
      morbidity and mortality. DESIGN: A multicentre randomised controlled trial.
      METHODS: Between January 2007 and November 2009, 28 patients with severe aorto
      iliac occlusive disease (TASC II C or D) were randomised between laparoscopic and
      open approach at one community hospital and one university hospital (TASC = Trans
      Atlantic Inter-Society Consensus on the Management of Peripheral Arterial
      Disease). RESULTS: The operation time was longer for the laparoscopic approach
      (mean 4 h 19 min (2 h 00 min to 6 h 20 min) vs. 3 h 30 min (1 h 42 min to 5 h 11
      min); p = 0.101)). Nevertheless, postoperative recovery and in-hospital stay were
      significantly shorter after laparoscopic surgery. Also oral intake could be
      restarted earlier (mean 20 h 34 min (6 h 00 min to 26 h 55 min) vs. 43 h 43 min
      (19 h 40 min to 77 h 30 min); p = 0.00014)) as well as postoperative mobilisation
      (walking) (mean 46 h 15 min (16 h 07 min to 112 h 40 min) vs. mean 94 h 14 min
      (66 h 10 min to 127 h 23 min); p = 0.00016)). Length of hospitalisation was
      shorter (mean 5.5 days (2.5-15) vs. mean 13.0 days (7-45); p = 0.0095)). Visual
      pain scores and visual discomfort scores were both lower after laparoscopic
      surgery. Also return to normal daily activities was achieved earlier. There were
      no major complications in both groups. CONCLUSION: Laparoscopic aortobifemoral
      bypass surgery for aorto-iliac occlusive disease is a safe procedure with a
      significant decrease in postoperative morbidity and in-hospital stay and earlier
      recovery.

PMID- 22386383
TI  - Cost and effectiveness of laser with phlebectomies compared with foam
      sclerotherapy in superficial venous insufficiency. Early results of a randomised
      controlled trial.
AB  - OBJECTIVES: Quantify endovenous laser ablation (EVLA) with concurrent
      phlebectomies and ultrasound-guided foam sclerotherapy (UGFS) in cost and
      effectiveness at 3 weeks and 3 months. DESIGN: Single-centre, prospective,
      randomised controlled trial. PATIENTS: One hundred patients (100 legs), C(2-6),
      age 21-78, M:F 42:58, with primary varicose veins received either EVLA under
      local anaesthetic or UGFS. METHODS: Assessments included duplex, Aberdeen
      varicose vein questionnaire (AVVQ), venous clinical severity score (VCSS), venous
      filling index (VFI), visual analogue 7-day pain score and analgesia requirements.
      Additional treatments with UGFS were performed, if required. Micro-costing, using
      individually timed treatments, was based on consumables, staff pay and overheads.
      RESULTS: Changes in AVVQ, VCSS and VFI values (3 months) did not demonstrate any
      significant difference between groups. At 3 months, the above-knee GSV occlusion
      rate (without co-existing reflux) was not significantly different between the
      groups (74% vs 69%; EVLA vs UGFS; P = .596). Of the 9 haemodynamic failures in
      each group, 7 EVLA patients and 4 UGFS patients had co-existing cross-sectional
      above-knee GSV occlusion at some point. However, UGFS significantly outperformed
      EVLA in cost, treatment duration, pain, analgesia requirements and recovery.
      CONCLUSIONS: UGFS is 3.15 times less expensive than EVLA (L230.24 vs L724.72)
      with comparable effectiveness but 56% (versus 6%) required additional foam
      (ISRCTN:03080206).

PMID- 22386384
TI  - Treatment of aortic arch aneurysms with a modular transfemoral multibranched
      stent graft: initial experience.
AB  - OBJECTIVES: To present initial experience with a new modular transfemoral
      multibranched stent graft for treating aortic arch aneurysms. METHODS: Six
      patients, considered high risk for open surgery, were treated with custom made
      branched stent grafts. All patients had a staged left carotid subclavian bypass
      before the endovascular procedure. Each branched graft had a 12 mm side branch
      for the innominate artery and an 8 mm side branch for the left common carotid
      artery. RESULTS: Four patients out of six had uneventful placement of the
      prostheses, with successful exclusion of their aneurysms. One patient developed a
      type I endoleak that was managed successfully with coiling and gluing of the
      aneurysm sac. In one patient, cannulation of the innominate branch was
      unsuccessful and an extra-anatomic bypass was necessary to perfuse the right
      carotid and vertebral arteries. This patient developed a stroke, while one more
      suffered a right cerebellar infarct. CONCLUSION: We have demonstrated the
      technical feasibility of a modular transfemoral branched stent graft for
      treatment of aortic arch aneurysms. The method is relatively safe based on
      initial experience. More cases and long-term follow up are necessary to evaluate
      the efficacy and safety of this new device.

PMID- 22386385
TI  - Preoperative duplex vein mapping (DVM) reduces costs in patients undergoing
      infrainguinal bypass surgery: results of a prospective randomised study.
AB  - OBJECTIVES: Surgical site infections (SSIs) after bypass procedures provoke major
      costs. The aim of this prospective randomised trial was to assess if preoperative
      duplex vein mapping (DVM) reduces costs generated by SSI. MATERIALS/METHODS:
      Patients undergoing primary infrainguinal bypass were randomised to DVM of the
      ipsilateral greater saphenous vein (group A) or none (group B). Costs were
      calculated by the hospital's accounting department. RESULTS: From December 2009
      to April 2011, 130 patients (65 each group) were enrolled. Both cohorts were
      equal regarding demographics, risk factors and costs for primary bypass surgery,
      respectively. SSIs were classified minor (A: n = 13 vs. B: n = 13, P = n.s.) and
      major (A: n = 1 vs. B: n = 12, P = .0154). Preoperative DVM was the only
      significant factor to prevent major SSI (P = .011). Theatre costs for SSI: A: 537
      ? versus B 6553 ? (P = .16). Recovery room/intensive care unit (ICU) costs for
      SSI: A: 0 ? versus B: 8016 ? (P = .22). Surgical ward costs for SSI: A: 2823 ?
      versus B: 22 386 ? (P = .011). Costs for outpatient visits due to SSI: A: 6265 ?
      versus B: 12 831 ? (P = .67). Total costs of patients without SSI: 8177 ? versus
      major SSI: 10 963 ? (P < .001). CONCLUSION: DVM significantly reduces costs
      generated by re-admission in patients suffering from major SSI.

PMID- 22386386
TI  - Endovascular repair of abdominal aortic aneurysm does not improve early survival
      versus open repair in patients younger than 60 years.
AB  - OBJECTIVES: Multiple randomised trials have demonstrated lower perioperative
      mortality after endovascular aneurysm repair (EVAR) compared to open surgical
      repair for infrarenal abdominal aortic aneurysms (AAAs). However, in these trials
      the mortality advantage for EVAR is being lost within 2 years of repair and the
      patients evaluated are relatively older with no study specifically comparing EVAR
      and open repair for patients younger than 60 years of age. DESIGN: A
      retrospective analysis of prospectively collected data. MATERIALS AND METHODS:
      Patients younger than 60 years of age who underwent EVAR and open surgical repair
      for elective infrarenal AAA were identified from the 2007-09 National Surgical
      Quality Improvement Program (NSQIP) - a prospective database maintained at 237
      centres across the United States. Univariate and multivariate analyses were
      performed. RESULTS: Of the 651 patients, 369 (56.7%) underwent EVAR and 282
      (43.3%) underwent open repair. Thirty-day mortality for EVAR and open repair were
      1.1% and 0.4%, respectively. This was not significantly different on univariate
      (P = 0.22) as well as multivariate (P = 0.69) analysis after controlling for
      other co-morbidities. On multivariate analysis, body mass index, history of
      stroke and bleeding disorder prior to surgery were associated with a higher 30
      day mortality after AAA repair (combined open and EVAR). CONCLUSIONS: These
      contemporary results demonstrate that the 30-day mortality rate after open repair
      is similar to that after EVAR in patients younger than 60 years with infrarenal
      AAA.

PMID- 22386388
TI  - The STOP-BANG questionnaire was a useful tool to identify OSA during
      epidemiological study in Sao Paulo (Brazil).

PMID- 22386387
TI  - A digital program informs low-income caregivers of preschool-age children about
      family meals.
AB  - OBJECTIVE: To evaluate the digital program, Mealtime is Family Time, as a means
      of educating caregivers of preschoolers on the importance of family meals within
      the division of feeding responsibility framework. METHODS: Descriptive design
      using 2 approaches: focus group program review and discussion or self-report
      survey after independent program review in low-income venues. All participants
      completed an inventory of child feeding practices. RESULTS: About 75% of feedback
      survey respondents (n = 147) found the program understandable, easy to read, and
      helpful and expressed interest in child cues of hunger and satiety. Focus group
      findings corroborated program utility and were congruent with need for division
      of feeding responsibility implementation. For example, 39% of respondents
      reported that children must always or often taste mealtime food. CONCLUSIONS AND
      IMPLICATIONS: Education about family meals and child feeding is critical;
      Mealtime is Family Time was well received by this low-income audience. Further
      development to measure practice of the division of feeding responsibility is
      warranted.

PMID- 22386389
TI  - Resident's corner, a new free-access feature in Urology.

PMID- 22386390
TI  - The impact of shock wave lithotripsy on male fertility: a critical analysis of
      existing evidence.
AB  - We review the literature about the impact of shock wave lithotripsy (SWL) on male
      reproduction. Studies investigating the in vitro effect of shock waves on semen
      samples indicate that spermatozoa are vulnerable to SWL. According to animal
      studies, intratesticular bleeding is common, but pregnancy rates are not affected
      by shock waves. In the clinical setting, SWL causes an acute deterioration in
      sperm quality, but semen parameters return to baseline 3 months later. Long-term
      data on male fertility (ie, pregnancy rates) after SWL have yet to be reported
      and the significance of preexisting infertility has not been elucidated to date.

PMID- 22386391
TI  - Reproducibility of electrical sensory testing in lower urinary tract at weekly
      intervals in healthy volunteers and women with non-neurogenic detrusor
      overactivity.
AB  - OBJECTIVE: To evaluate the reproducibility of a standardized technique of current
      perception threshold measurements with square wave and sine wave current, with
      monopolar and bipolar electrodes in a cohort of patients with overactive bladder
      (OAB) and healthy volunteers. METHODS: We enrolled 6 female nulliparous healthy
      volunteers and 11 female patients with OAB. Current perception threshold
      measurements of the bladder were performed using several techniques. The same
      sequence was used for all 3 measurements performed at weekly intervals to assess
      the reproducibility. An intraclass correlation coefficient >0.75 was considered
      as very good reproducibility. RESULTS: All the different stimulation forms were
      well tolerated by all participants and all experienced stimulation at 2.5-Hz and
      95-Hz square wave current. The results with sine wave current showed less uniform
      results. The intraclass correlation showed the greatest reproducibility with
      bipolar stimulation at a current of 95 Hz. Sine wave current at 5 Hz and 250 Hz
      showed low reproducibility. Bipolar stimulation had significantly lower
      thresholds than monopolar stimulation (P < .0001). No significant differences
      were found between the healthy subjects and the patients with OAB for the 4
      settings. CONCLUSION: In the healthy volunteers and patients with OAB, the
      determination of the current perception threshold in the bladder using a
      standardized method is feasible and well tolerated, with both bipolar and
      monopolar stimulation. In our study, square wave current showed strong
      reproducibility at weekly intervals at 2.5 Hz and 95 Hz. However, sinusoid
      current gave weak reproducibility.

PMID- 22386392
TI  - Robotic vs abdominal sacrocolpopexy: 44-month pelvic floor outcomes.
AB  - OBJECTIVE: To evaluate longer-term clinical outcomes after robotic vs abdominal
      sacrocolpopexy for the treatment of advanced pelvic organ prolapse (POP).
      MATERIAL AND METHODS: This was a retrospective cohort assessment of women
      undergoing either robotic or abdominal sacrocolpopexy between March 2006 and
      October 2007. Pelvic floor support was measured using Pelvic Organ Prolapse
      Quantification (POP-Q) examination, and pelvic floor function was assessed via
      validated questionnaires, including the Pelvic Floor Distress Inventory (PFDI
      20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12). RESULTS:
      The analysis included 51 subjects: 23 robotic and 28 abdominal. Mean time since
      surgery was 44.2 +/- 6.4 months. Postoperative POP-Q improved similarly from
      baseline in both the robotic and abdominal groups: C (-8 vs -7), Aa (-2.5 vs 
      2.25), Ap (-2 vs -2) (all P >.05 based on route of surgery). Pelvic floor
      function also improved similarly in both groups: PFDI-20 (61.0 vs 54.7), PFIQ-7
      (19.1 vs 15.7), with high sexual function PISQ-12 (35.1 vs 33.1) (all P >.05
      based on route of surgery). Two mesh exposures occurred in each group for a rate
      of 8% and 7%, respectively. CONCLUSION: Robotic sacrocolpopexy demonstrates
      similar long-term outcomes compared with abdominal sacrocolpopexy. The robotic
      approach offers an effective treatment alternative to abdominal sacrocolpopexy
      for the lasting treatment of advanced POP.

PMID- 22386393
TI  - Head to head comparison of nomograms predicting probability of lymph node
      invasion of prostate cancer in patients undergoing extended pelvic lymph node
      dissection.
AB  - OBJECTIVE: To validate the Briganti nomogram and compare it with 2 current lymph
      node invasion (LNI) nomograms (the Cagiannos nomogram and the updated 2007 Partin
      tables). The Briganti nomogram predicts the probability of LNI in patients
      undergoing extended pelvic lymph node dissection (EPLND) during radical
      prostatectomy for prostate cancer. METHODS: Irrespective of the risk of LNI, 173
      consecutive patients were treated for localized prostate cancer with radical
      laparoscopic prostatectomy and EPLND. The area under the receiver operating
      characteristics curve was used to estimate the predictive accuracy of the
      nomograms, and calibration plots were used for comparisons between the predicted
      and observed probabilities of LNI. RESULTS: The median number of nodes removed
      was 15 (range 10-34). Of the 173 patients, 12 (6.9%) had LNI. The Briganti
      nomogram achieved a receiver operating characteristic curve of 0.88 versus 0.83
      with the Cagiannos nomogram and 0.84 with the 2007 Partin tables. The difference
      in predictive accuracy was not statistically significant (P < .2). The Briganti
      nomogram showed only minor departures from the ideal predictions in the low-risk
      range and the Cagiannos nomogram showed major departures from the ideal
      predictions for the entire risk range. CONCLUSION: The Briganti nomogram provides
      highly accurate predictions of the risk of LNI after EPLND. Its performance
      tended to be increased without being significantly better. The other tools also
      performed reasonably well but underestimate the true risk of LNI. We recommend
      the use of these tools to identify patients at low risk of LNI for whom EPLND can
      be safely spared.

PMID- 22386394
TI  - Pelvic floor electrical stimulation for postprostatectomy urinary incontinence: a
      meta-analysis.
AB  - OBJECTIVE: To evaluate the role of electrical stimulation (ES) in the recovery of
      postprostatectomy urinary incontinence (UI). METHODS: We performed a meta
      analysis of all available randomized controlled trials comparing ES enhanced
      pelvic floor muscle training (PFMT) with PFMT alone for postprostatectomy UI. We
      separated in the analysis the continence rate within 3 months or longer than 6
      months after operation, which stand for the early and late recovery of UI after
      operation, respectively. Relative risk (RR) reductions and their 95% confidence
      intervals (CIs) were calculated for categorical outcomes. RESULTS: Four studies
      randomizing 210 cases were included in the meta-analysis. Three studies enrolling
      186 cases reported the continence rate within 3 months after radical
      prostatectomy. The pooled analysis did not show that ES improved early recovery
      of UI better than did PFMT (RR 1.21; 95% CI = 0.95-1.54, P = .12). All 4 studies
      provided data for 6-12 months after RP; the pooled analysis did not show a
      relative benefit (RR = 1.03; 95% CI = 0.88-1.20, P = .73). CONCLUSION: Based on
      available evidence, ES enhanced PFMT did not improve the return to continence
      more than PFMT in men with postprostatectomy UI.

PMID- 22386395
TI  - Rectal cultures before transrectal ultrasound-guided prostate biopsy reduce post
      prostatic biopsy infection rates.
AB  - OBJECTIVE: To test our hypothesis that a targeted rectal screening protocol
      before transrectal ultrasound (TRUS)-guided biopsy would potentiate streamlined
      prophylaxis, thereby reducing postbiopsy infectious rates while minimizing
      unnecessary broad-spectrum antibiotic use. To this end, we instituted
      preprocedure rectal cultures in an effort to identify fluoroquinolone (FQ)-
      resistant flora using selective media to optimally direct targeted prophylactic
      antibiotic administration. The inexorably increasing prevalence of multidrug
      resistant microorganisms, notably extended spectrum beta lactamase (ESBL)
      producing and FQ-resistant Enterobacteriaceae has increased the post-TRUS
      prostatic biopsy infection rates, including life-threatening sepsis. METHODS: A
      total of 235 rectal swabs were obtained and plated directly onto MacConkey agar
      plates containing 10-MUg/mL ciprofloxacin. Following the screening procedure,
      antimicrobial susceptibility results were used to develop a customized antibiotic
      prophylaxis regimen to be administered before biopsy. Following the biopsy
      procedure, the patients were seen in follow-up within 7 days, and information was
      gathered on potential adverse effects, clinical appointments for infections, and
      potential antibiotics received. RESULTS: Thirty-two-patients (14%) had FQ
      resistant isolates (most Escherichia coli), and 3 (1.3%) were ESBL-producing
      isolates. There were no infectious complications identified in this period,
      (compared with 3 septic complications among 103 biopsies in the 4 months
      preceding the study). CONCLUSION: Rectal cultures obtained before TRUS biopsy,
      using selective media to identify FQ-resistant Enterobacteriaceae, facilitate
      targeted antibiotic prophylaxis, and appear to be highly efficacious in reducing
      infectious complications.

PMID- 22386397
TI  - Editorial comment.

PMID- 22386398
TI  - Clinical significance of routine urinary bacterial culture after transurethral
      surgery: results of a prospective multicenter study.
AB  - OBJECTIVES: The objective of this study was to evaluate the prevalence and the
      clinical outcomes of asymptomatic postoperative bacteriuria after transurethral
      operations, along with the need for postoperative urinalysis. METHODS: A
      prospective study of 456 patients who underwent transurethral resection of the
      prostate (TURP) or transurethral resection of the bladder (TURB) at 2 urological
      centers in France, between January 2008 and March 2009. All patients had urine
      cultures preoperatively, on the day of catheter removal, and at 1 month
      postoperatively. Only patients with symptoms suggesting a urinary tract infection
      were treated. Univariate logistic regression and multiple logistic regression
      were used to estimate the odds ratios and P values. RESULTS: TURP was performed
      in 217 patients, and TURB was performed in 239 patients. A total of 35 patients
      (7.6%) had positive postoperative urine cultures. Only 9 patients (1.9%) were
      treated. Patient age and postoperative catheterization duration were identified
      as risk factors for postoperative bacteriuria (OR = 1; 95% CI = 1.0-1.1; P = .03
      and OR = 3.6; 95% CI = 2.3-5.7; P = .0001, respectively), and preoperative
      bacteriuria was not risk factor for postoperative bacteriuria (OR = 0.9; 95% CI =
      0.3-1.4; P = .8). A total of 45 patients had a positive urinalysis at 1 month,
      and 29 presented an infectious complication during follow-up. A positive
      postoperative urinalysis was not a risk factor either for a positive urinalysis
      at 1 month or for an infectious complication during follow-up (OR = 3.2; 95% CI =
      0.4-22.4, P = .2 and OR = 1.4; 95% CI = 0.4-4.9, P = .5, respectively).
      CONCLUSIONS: Based on our study findings, postoperative bacteriuria is not a risk
      factor for infectious postoperative complications. Therefore, routine
      postoperative urinalysis should be advocated only in symptomatic patients.

PMID- 22386399
TI  - Laparoscopic radical nephrectomy for large renal masses: critical assessment of
      perioperative and oncologic outcomes of stage T2a and T2b tumors.
AB  - OBJECTIVE: To analyze the perioperative and oncologic outcomes of >7 cm renal
      tumors treated with laparoscopic radical nephrectomy (LRN) at a high-volume
      academic center. The indications for LRN have expanded to include larger (>7 cm)
      lesions. METHODS: The Institutional Minimally Invasive Urologic Surgery Database
      (1994 to the present) was reviewed for patients undergoing LRN for >7-cm masses
      (American Joint Committee on Cancer clinical Stage T2N0M0). RESULTS: Of 200
      patients, 138 (69.0%) had tumors >7.0-10 cm and 62 (31.0%) had tumors >10 cm. The
      patients with tumors >10 cm presented more often with symptoms, most often
      hematuria, and more often had high-grade tumors (68% vs 44%, P = .005). Also, a
      greater proportion were papillary renal cell carcinoma (23% vs 14%, P = .09) and
      were more often upstaged (21% vs 9%, P = .02). Of the 200 tumors, 74 (37%) were
      upstaged, 58 (29%) with perinephric extension and 26 (13%) with renal vein
      invasion. Larger tumors had greater blood loss on average (406 vs 288 mL,
      respectively, P = .1) and were converted to open surgery more often (13.8% vs
      2.1%, P = .001). A total of 47 patients (22.3%) experienced a postoperative
      complication. The 5-year recurrence-free survival and cancer-specific survival
      rate was 62.4% and 92.9%, respectively. The significant predictors of recurrence
      free survival in the multivariate model were clear cell histologic type, high
      Fuhrman grade, renal vein invasion, and perinephric extension. Of note, pT2b was
      not a predictor of recurrence. CONCLUSION: LRN can have favorable perioperative
      and oncologic outcomes for large (>7 cm) renal masses, with an open conversion
      rate and complication rate of 5% and 20%, respectively. Clear cell histologic
      features, high-grade tumors, renal vein invasion, and perinephric extension, but
      not tumor size, were poor prognostic indicators in this cohort.

PMID- 22386400
TI  - Editorial comment.

PMID- 22386401
TI  - Comparison of single-surgeon series of transperitoneal laparoendoscopic single
      site surgery and standard laparoscopic adrenalectomy.
AB  - OBJECTIVE: To assess the feasibility, safety, and efficacy of transperitoneal
      laparoendoscopic single-site (LESS) adrenalectomy and determine whether it shows
      any objective advantage compared with standard laparoscopy. METHODS: From August
      2009 to May 2011, 13 transperitoneal LESS adrenalectomies were performed through
      a 2-3-cm skin incision using the TriPort access system. This cohort was compared
      with a contemporary 1:2 matched-pair group of 26 patients undergoing standard
      laparoscopic adrenalectomy by the same urologist. The perioperative outcomes,
      including cosmetic satisfaction scores, were statistically analyzed. RESULTS: The
      2 groups were comparable with respect to patient demographics, estimated blood
      loss, and postoperative hospitalization (P > .05). The LESS procedures had a
      longer mean operative time (148.5 vs 112.9 minutes, P = .032) but a significantly
      lower postoperative visual analog pain scale score (2.3 vs 3.7, P = .001), fewer
      patients requiring analgesics (30.8% vs 73.1%, P = .011), and an earlier
      resumption of oral intake (21.6 vs 26.0 hours, P = .002). The mean length of the
      scar in the LESS group was much smaller (2.3 vs 5.9 cm, P < .0001) with a
      statistically significant greater mean cosmetic satisfaction score (9.5 vs 9.1, P
      = .042). CONCLUSION: The perioperative outcomes of transperitoneal LESS
      adrenalectomy for small adrenal tumors were comparable to those with the standard
      laparoscopic approach. It also provides better postoperative pain control, faster
      recovery of bowel function, and better cosmetic satisfaction than standard
      laparoscopy, albeit with a longer operative time.

PMID- 22386403
TI  - Editorial comment.

PMID- 22386404
TI  - Outcomes of laparoscopic and robotic radical cystectomy in the elderly patients.
AB  - OBJECTIVE: To compare the perioperative outcomes of laparoscopic/robotic radical
      cystectomy (LRRC) for urothelial cancer of bladder (UCB) between elderly (>= 70
      years) and younger (<70 years) patients. MATERIALS AND METHODS: A retrospective
      review of 146 patients who underwent LRRC between 2003 and 2010 at 2 academic
      institutions (Cleveland, Ohio, United States and Toulouse, France) was performed.
      Of these, 74 patients were classified as elderly (>= 70 years) and 72 patients
      were considered younger (<70 years). Perioperative outcomes, final pathology
      results, overall survival (OS), and cancer specific survival (CSS) were compared
      between the 2 groups. RESULTS: Both groups had similar clinical stage at
      diagnosis, American Society of Anesthesiologists score, body mass index, and
      gender distribution. Ileal conduit-type diversion was favored in the older vs
      younger group, 84% vs 36%, respectively. Overall conversion rate to open
      procedures was 4% in both groups. Perioperative complication rate was not
      significantly different between the younger and older patients. Positive margin
      rate was 5% in both groups. The 5-year OS for older and younger patients was 75%
      and 87%, respectively (P = .03), and the 5-year CSS for the 2 groups was 51% and
      54%, respectively (P = .7). CONCLUSION: Laparoscopic/robotic radical cystectomy
      in the elderly does not have worse perioperative complications or pathologic
      outcomes compared with younger patients and therefore can be offered as treatment
      option in select older patients.

PMID- 22386405
TI  - Radical prostatectomy with robot-assisted radical prostatectomy and laparoscopic
      radical prostatectomy under low-dose aspirin does not significantly increase
      blood loss.
AB  - OBJECTIVE: To determine whether maintaining use of low-dose aspirin confers a
      higher risk of bleeding events in patients undergoing laparoscopic or robot
      assisted radical prostatectomy. There is no consensus on maintaining or
      withdrawing aspirin in these patients. METHODS: Consecutive patients undergoing
      laparoscopic and robot-assisted radical prostatectomy between January 2009 and
      December 2010 were included in a prospective cohort study. Among them, 54 aspirin
      treated patients were compared with 569 non-aspirin-treated patients. We
      evaluated the between-group difference in bleeding event: intraoperative blood
      loss >= 700 ml and/or need for transfusion and/or postoperative hemorrhagic
      complication (symptomatic abdominal wall hematomas, major bleeding requiring
      reoperation). Differences in each component of the bleeding event, in hemoglobin
      level changes, and hospital stay length were also evaluated. Patients' data were
      compared using the chi(2) or Fisher exact test for categorical variables and the
      Student t test or Mann-Whitney test for continuous variables. RESULTS: A bleeding
      event occurred in 18 (33.3%) aspirin-treated patients and 176 (32.5%) non-aspirin
      treated patients (P = .66). Median blood loss was similar in the 2 groups
      (aspirin: 450 ml, 50-7100 ml; no aspirin: 450 ml, 100-2800 ml; P = .93). Aspirin
      was not associated with a significant hemoglobin level variation (median
      decrease, 2.9 g/dL with aspirin and 3.2 g/dL without aspirin, P = .23). Median
      hospital length of stay, rates of blood transfusion, and postoperative
      hemorrhagic complications were similar in the 2 groups. CONCLUSION: Laparoscopic
      and robot-assisted radical prostatectomy can be performed safely without
      discontinuing aspirin, as this policy does not increase significantly blood loss,
      blood transfusion requirements, postoperative hemorrhagic complications. or
      hospital length of stay.

PMID- 22386406
TI  - Cavernosal nerve preservation during robot-assisted radical prostatectomy is a
      graded rather than an all-or-none phenomenon: objective demonstration by
      assessment of residual nerve tissue on surgical specimens.
AB  - OBJECTIVE: To demonstrate the existence of different degrees of nerve sparing
      (NS) (graded NS) by comparing the surgeon's intent of NS with the residual nerve
      tissue on prostatectomy specimens. METHODS: We performed a prospective study of
      133 consecutive patients who underwent robot-assisted radical prostatectomy in
      January and February of 2011. The surgeon graded the amount of NS
      intraoperatively independently for either side as follows: 1, no NS; 2, <50% NS;
      3, 50% NS; 4, 75% NS; and 5, >= 95% NS. A pathologist who was unaware of the
      surgeon's score measured the area of residual nerve tissue on the posterolateral
      surface of the prostate. RESULTS: A greater NS score correlated significantly
      with a decreasing area of residual nerve tissue on the prostatectomy specimens (P
      < .001). Overall, the area of residual nerve tissue on the prostatectomy
      specimens was significantly different among the NS groups (P < .001). On specific
      intergroup analysis, significant differences were found in the area of residual
      nerve tissue on the prostatectomy specimens between the greater NS groups: NS
      score 3 versus 4, median 13 mm(2) (interquartile range [IQR] 7-23) versus 3 mm(2)
      (IQR 0-8; P = .01); NS score 4 versus 5, median 3 mm(2) (IQR 0-8) versus 0.5
      mm(2) (IQR 0-2; P = .001). CONCLUSION: Subjective NS classification using the
      surgeon's intraoperative perception correlated significantly with the area of
      residual nerve tissue on the prostatectomy specimens determined by the
      pathologist. It is possible to intentionally tailor the amount of NS performed at
      surgery. This finding demonstrates that NS is a graded rather than an all-or-none
      phenomenon that can even go beyond the traditional concept of complete, partial,
      or no NS.

PMID- 22386407
TI  - Multicenter pathophysiologic investigation of erectile dysfunction in clinic
      outpatients in China.
AB  - OBJECTIVE: To assess the pathophysiologic composition and age structure of
      erectile dysfunction (ED) in men visiting outpatient clinics in China. METHODS:
      We studied 3327 consecutive ED outpatients (median age 39 years) from 2006 to
      2010 in the 5 training hospitals in China. Every patient was independently
      evaluated by an experienced urologist/andrologist using comprehensive diagnostic
      procedures. The simplified International Index of Erectile Function was used to
      assess the severity of ED. RESULTS: Most patients (95.0%) were <60 years old, and
      none were >70 years old. The psychogenic patients were younger and had greater
      percentage than any other patients. Vasculogenic factors were a major etiology of
      organic ED. A significant difference was found in the age distribution between
      the patients with psychogenic ED and those with organic ED (P = .000). Diabetes,
      hypertension, coronary artery disease, and hyperlipidemia played significant
      roles in affecting the severity of ED in a statistical model, including age. The
      International Index of Erectile Function scores decreased with age (rs = -0.199,
      P = .000). Moreover, the percentage of severe and moderate cases increased with
      age (P = .003 and P = .002, respectively). However, the constituent ratio of
      patients sharply declined from 30.3% to 4.5% with age. CONCLUSION: The number of
      men visiting outpatient clinics with psychological ED is greater than the number
      with organic causes in China. The age of the Chinese patients with ED who seek
      medical help is young and this is mainly because of inadequate sex education to
      young men and because most older patients are reluctant to visit the hospital
      just for the loss of erectile function.

PMID- 22386408
TI  - Functional analysis of elective nephron-sparing surgery vs radical nephrectomy
      for renal tumors larger than 4 cm.
AB  - OBJECTIVE: To preserve renal function, nephron sparing surgery (NSS) for renal
      tumors should be performed. Little is known about perioperative morbidity and
      long-term functional outcome of patients after elective NSS compared with radical
      nephrectomy (RN) in renal tumors >4 cm. MATERIALS AND METHODS: Eight-hundred
      twenty-nine patients were treated with either RN (n = 641) or NSS (n = 188) for
      renal tumors >4 cm. After pairing the cohort for age, grading, TNM, size, gender,
      and preoperative renal function and excluding patients with imperative indication
      and metastases, 247 patients remained for functional analysis. Serum creatinine
      (SCr) values were used to estimate glomerular filtration rate (eGFR) via
      Modification of Diet in Renal Disease. Chronic kidney disease (CKD) was defined
      as eGFR <60 mL/min/1.73 m(2) and regression analyses were used to identify
      clinical risk factors for CKD and perioperative complications stratified by the
      Clavien-Dindo score. RESULTS: The Charlson comorbidity index was similar between
      patients undergoing NSS (n = 101) and RN (n = 146) (P = .583). The complication
      rates did not differ significantly between both groups (P = .091). Age (OR 0.94,
      P = .009), ASA score 3+4 (OR 3.55, P = .004), RN (OR 10.75, P < .001), and
      preoperative eGFR (OR 1.06, P < .001) were independent risk factors for
      developing CKD postoperatively, whereas tumor size had no impact (OR 1.01, P =
      .245). Overall survival was comparable between the groups (P = .896). CONCLUSION:
      Although overall survival was similar, patients undergoing RN for renal tumors >4
      cm had a significantly higher risk of developing CKD than patients treated with
      NSS. Complication rate did not differ significantly between both groups, even for
      tumors >7 cm. Our findings support elective NSS for tumors >4 cm, whenever NSS is
      technically feasible for maintaining renal function.

PMID- 22386409
TI  - Editorial comment.

PMID- 22386411
TI  - High rate of pathologic upgrading at nephroureterectomy for upper tract
      urothelial carcinoma.
AB  - OBJECTIVE: To determine the association between endoscopic biopsy grade and the
      final pathologic characteristics at nephroureterectomy for upper tract urothelial
      carcinoma (UTUC). Endoscopic biopsy is an important tool for patients with UTUC
      because the results can influence the management decisions. METHODS: We
      identified 481 patients who had undergone nephroureterectomy for UTUC at the Mayo
      Clinic from 1995 to 2008. Of these patients, 184 underwent endoscopic cup or
      brush biopsy before nephroureterectomy. The biopsy tumor grade was then compared
      with the tumor grade and stage obtained at nephroureterectomy. RESULTS: Of the
      184 patients, 27 (15%) had nondiagnostic biopsy results and 21 (11%) had positive
      biopsy results with no histologic grade. Of the 24 patients with grade 1 tumors
      on biopsy, 23 (96%) had the tumor upgraded on the final pathologic examination:
      16 (67%) to grade 2 and 7 (29%) to grade 3. Similarly, 23 (40%) of 57 grade 2
      tumors on biopsy were upgraded to grade 3 after nephrouretecomy. Only a few
      patients, 7 (4%) of 184, were found to have a lower histologic grade on the final
      pathologic examination. The number of patients with invasive UTUC for endoscopic
      grade 1, 2, and 3 tumors was 9 (38%) of 24, 31 (54%) of 57, and 47 (85%) of 55,
      respectively. CONCLUSION: In the context of patients selected for
      nephroureterectomy, we observed a greater than expected rate of tumor upgrading
      and invasive disease, particularly in those with low-grade tumors at biopsy.
      These findings should be considered when electing to use conservative or
      endoscopic management of low-grade UTUC.

PMID- 22386412
TI  - Influence of urinary tract instrumentation and inflammation on the performance of
      urine markers for the detection of bladder cancer.
AB  - OBJECTIVE: To evaluate the impact of inflammation and sampling on cytology,
      immunocytology, and fluorescence in situ hybridization (FISH) in comparison with
      NMP22 in hematuria patients. The specificity of urine markers for urothelial
      cancer is subject to exogenous factors. There is evidence that nuclear matrix
      protein 22 (NMP22) is influenced by urinary tract infection and instrumented
      urinary sampling (IUS). METHODS: Samples from 1386 patients with histologic work
      up were included. Cytology, immunocytology, FISH, and NMP22-enzyme-linked
      immunosorbent assay were performed. The presence of inflammation was evaluated by
      microscopy. The method of urine sampling was recorded in all cases. Any type of
      urinary tract manipulation was considered as IUS. False-positive results were
      compared with regard to the presence or absence of inflammation and mechanical
      manipulation. RESULTS: In all, 1050 (75.7%) patients had no evidence of
      urothelial cancer. NMP22 results were false positive in 74.3% and 38.4% of
      patients with and without IUS (P < .0001). False-positive test rates of cytology,
      immunocytology, and FISH were not increased after manipulation. Inflammation led
      to a rise in false-positive NMP22 test results (85.3% vs 61.4%, P < .0001). The
      presence of inflammation did not change the rate of false-positive cytology,
      immunocytology, and FISH results. CONCLUSION: This is the first study to
      investigate the impact of inflammation and IUS on cell-based urine markers. In
      contrast to the protein test NMP22, these factors did not impair the performance
      of cell-based tests. Hence, patients with positive cytology, immunocytology, and
      FISH results should undergo diagnostic work-up, even in the case of concomitant
      inflammation or IUS.

PMID- 22386414
TI  - Editorial comment.

PMID- 22386415
TI  - Editorial comment.

PMID- 22386417
TI  - Engagement of integrinbeta1 induces resistance of bladder cancer cells to
      mitomycin-C.
AB  - OBJECTIVE: To identify whether integrinbeta1 subunit is responsible for the
      resistance of bladder cancer cell to the therapeutic drug mitomycin-C (MMC), when
      grown on fibronectin (FN). MATERIALS AND METHODS: The expression of integrinbeta1
      on bladder cancer T24 and 5637 cells was examined by the flow cytometer. The
      adhesion of cells to plates with the absence or presence of FN was determined.
      Analysis of apoptosis induced by MMC was assessed using the flow cytometer in
      combination with an integrinbeta1-blocking antibody or siRNA targeting the coding
      region of integrinbeta1. Western blot was used to study the expression change of
      integrinbeta1 and its downstream molecules. RESULTS: Bladder cancer T24 and 5637
      cells express high level of integrinbeta1 (87.3% +/- 2.3 and 90.1% +/- 1.9,
      respectively). Cellular adhesion to FN was significantly reduced by the blocking
      of integrinbeta1. Blocking or silencing of integrinbeta1 significantly abolished
      the drug resistance of cells grown on FN to MMC (P <.05) and inhibited the
      activation of survival signals phosphoinositide-3 kinase (PI3-K)/Akt. CONCLUSION:
      Integrinbeta1-mediated cellular adhesion to FN confers drug resistance to MMC on
      bladder cancer cells. Knockdown of integrinbeta1 may abolish the drug resistance
      phenotype and sensitize bladder cancer cells to MMC.

PMID- 22386418
TI  - Multiple rechallenges for castration-resistant prostate cancer patients
      responding to first-line docetaxel: assessment of clinical outcomes and
      predictive factors.
AB  - OBJECTIVE: To describe the feasibility and efficacy of multiple sequential
      rechallenges and analyze the predictive factors that may aid in selecting
      patients who are more likely to respond. Several studies have demonstrated the
      feasibility and activity of a single docetaxel rechallenge in patients with
      castration-resistant prostate cancer (CRPC), thus providing an additional
      opportunity for treatment in docetaxel-sensitive CRPC patients in clinical
      practice. MATERIALS AND METHODS: CRPC patients who completed first-line docetaxel
      therapy without disease progression have been offered a docetaxel rechallenge,
      and the responders have undergone further rechallenges until the appearance of
      docetaxel resistance. We assessed their clinical outcomes and evaluated all the
      variables potentially capable of predicting the response to rechallenge by means
      of uni- and multivariate analysis. RESULTS: Forty-six consecutive patients
      underwent 92 rechallenges. The overall biochemical response rate (prostate
      specific antigen [PSA] reduction >50%) was 66%. Median overall survival was 32
      months with a projected 2-year overall survival from the first docetaxel
      administration of 77.5%. Multivariate analysis showed that the time slope-log
      PSA, the time from the previous cycle, and the response to the previous cycle
      were predictive of the response to a rechallenge. CONCLUSION: A docetaxel
      rechallenge may be safely repeated several times in CRPC patients and in selected
      patients could improve disease control. The predictive factors found in our
      analysis may help select the most appropriate strategy in the light of the
      availability of active second-line drugs.

PMID- 22386416
TI  - Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide
      before radical prostatectomy for clinical T3 and T4 prostate cancer: update on
      Southwest Oncology Group Study 9109.
AB  - OBJECTIVE: To update the results with 10-year data of a phase II prospective
      trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide
      followed by radical prostatectomy for locally advanced prostate cancer (SWOG
      9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer
      is uncertain. MATERIALS AND METHODS: Sixty-two patients with clinical stage T3
      and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs
      T4 and by volume of disease (bulky >4 cm and nonbulky <= 4 cm). RESULTS: Fifty
      five of 61 eligible patients completed the trial with radical prostatectomy after
      neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate
      specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of
      >= 7. Among 41 patients last known to be alive, median follow-up is 10.6 years
      (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%)
      or died without progression (8/55, 15%) for a 10-year progression-free survival
      (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median
      survival has not been reached. The 10-year overall survival (OS) estimate is 68%
      (95% CI 56-80). CONCLUSIONS: In this small, prospective phase II study,
      neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by
      radical prostatectomy achieves long-term PFS and OS comparable with alternative
      treatments. This approach is feasible and may be an alternative to a strategy of
      combined radiation and ADT.

PMID- 22386419
TI  - 160-Watt lithium triboride laser vaporization versus transurethral resection of
      prostate: a prospective nonrandomized two-center trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of 160-W lithium triboride laser
      photoselective vaporization of the prostate (PVP) for the surgical treatment of
      benign prostatic hyperplasia compared with transurethral resection of the
      prostate (TURP). METHODS: From July 2010 to January 2011, a prospective
      nonrandomized study was performed. A total of 108 patients (57 underwent PVP and
      51 TURP) were included in the present study. All patients were preoperatively
      assessed by International Prostate Symptom Score, transrectal ultrasonography,
      uroflowmetry, and postvoid residual urine volume measurement. The perioperative
      parameters and complications were recorded. The patients were reassessed at 1, 3,
      and 6 months postoperatively. RESULTS: The mean operative time was 57.4 +/- 17.3
      minutes for TURP and 64.3 +/- 20.5 minutes for PVP (P = .044). A significant
      difference in favor of PVP was achieved for the catheter indwelling time and
      hospital stay time. Bleeding requiring blood transfusion in 8 patients, and
      transurethral resection syndrome was observed in 3 patients in the TURP group.
      Capsule perforation was observed in 5 patients in the TURP group. No severe
      perioperative complications were recorded in the PVP group. Finally, 4 patients
      in the TURP group and 1 patient in the PVP group experienced urethral stricture
      (P = .047). CONCLUSION: The results of the present study have shown that 160-W
      lithium triboride laser vaporization is more favorable in terms of perioperative
      safety and results in a shorter postoperative catheter time and shorter length of
      hospital stay than with TURP.

PMID- 22386420
TI  - Longitudinal changes of benign prostate-specific antigen and [-2]proprostate
      specific antigen in seven years in a community-based sample of men.
AB  - OBJECTIVE: To determine the longitudinal changes of benign prostate-specific
      antigen (BPSA) and [-2]proPSA and how these changes relate to the outcomes. These
      markers have been shown to be predictive of prostate cancer (CaP) and benign
      prostatic hyperplasia treatment; however, little is known about longitudinal
      changes in these markers. METHODS: In 1990, a 25% subsample from a cohort of
      white men aged 40-79 years, who were randomly selected from Olmsted County,
      Minnesota residents, completed a detailed clinical examination. BPSA and [
      2]proPSA were measured from frozen sera. The men were evaluated biennially
      (median follow-up 7 years; range 0-8.8). Mixed-effects regression models were
      used to estimate the longitudinal changes in the BPSA and [-2]proPSA levels
      overall and by outcomes. Spearman correlations were used to compare these changes
      with the baseline levels and the annualized changes in urologic measures.
      RESULTS: The median and 25th and 75th percentiles annualized percent change for [
      2]proPSA and BPSA was 3.7%, 2.5% and 5.2% and 7.3%, 6.8%, and 7.7%, respectively.
      The annualized percent change for both markers correlated with the baseline and
      annualized changes in PSA and prostate volume. The annualized percent change
      increased with increasing age decade for [-2]proPSA but not for BPSA. The rate of
      increase in [-2]proPSA was significantly greater for men who developed enlarged
      prostates (median 3.5%, 25th and 75th percentile 2.6% and 4.4%, respectively) or
      CaP (median 8.1%, 25th and 75th percentile 6.6% and 9.8%, respectively) compared
      with those who did not develop enlarged prostates (median 1.9%, 25th and 75th
      percentile 0.9% and 3.0%, respectively) or CaP (median 3.5%, 25th and 75th
      percentile 2.3% and 4.8%, respectively). CONCLUSION: BPSA and [-2]proPSA levels
      increase over time. The annualized percent change in [-2]proPSA increases with
      age and might be a useful predictor of CaP development.

PMID- 22386421
TI  - Editorial comment.

PMID- 22386422
TI  - Clinical predictors of testicular torsion in children.
AB  - OBJECTIVE: To distinguish the prognostic factors that decrease the probability of
      a negative exploration for "acute scrotum." In some institutes, patients with
      "acute scrotum" undergo immediate exploration after clinical evaluation. Because
      testicular torsion (TT) accounts only for a fraction of these cases, most infants
      can be treated conservatively. METHODS: We performed a retrospective study of all
      patients treated at our institute from January 2008 to December 2009 for the
      diagnosis of "acute scrotum." Differences between groups were calculated using
      the chi-square test or analysis of variance and Mann-Whitney-Wilcoxon test for
      univariate or multivariate analysis, expressed as odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: The data from 138 patients were analyzed.
      The mean age was 9 years, 8 months. Of the 138 patients, 19 (13.8%) had TT. This
      group was compared with the boys without TT at exploration. The patients with TT
      were older on average (11 years, 1 month vs 9 years, 1 month, p = .035). Pain for
      <24 hours (OR 4.2, 95% CI 1.3-13.4), nausea and/or vomiting (OR 21.6, 95% CI 4.9
      93.4), abnormal cremasteric reflex (OR 4.8 95% CI 0.7-35.2), and a high position
      of the testis (OR 18.0 95% CI 1.8-177.1) were associated with an increased
      likelihood of torsion. In the group of boys with >= 2 of these findings present,
      100% had TT at exploration, with 0% false-positive results. CONCLUSION: TT is
      uncommon among the group of boys treated for "acute scrotum." In particular, a
      pain duration <24 hours, nausea or vomiting, a high position of the testis, and
      an abnormal cremasteric reflex had a positive prognostic value for TT. A clinical
      score might help to avoid unnecessary explorations. In the future, we intend to
      test the diagnostic set described combined with ultrasonography.

PMID- 22386423
TI  - Analysis of robotic-assisted laparoscopic pyleloplasty for primary versus
      secondary repair in 119 consecutive cases.
AB  - OBJECTIVE: To analyze the outcomes of our robotic-assisted pyeloplasty series for
      primary ureteropelvic junction obstruction (UPJO) and compare them with our
      series of robotic-assisted pyeloplasty for secondary UPJO. The repair of
      secondary UPJO can pose additional challenges to surgeons. Robotic assistance
      could aid in these repairs. METHODS: Using an institutional review board-approved
      database, we reviewed 119 consecutive patients who had undergone robotic-assisted
      laparoscopic pyeloplasty at our institution during an 8-year period (May 2002 to
      February 2010). Data were collected in a combined retrospective and prospective
      manner. The patients were stratified into primary repair and secondary repair for
      the primary analysis. The patients were also stratified into those with stones
      and those without stones for the secondary analysis. We compared the demographic,
      operative, postoperative, and radiographic outcomes. Student's t test and
      Pearson's chi-square correlation were used for statistical analysis of continuous
      and categorical variables, respectively. RESULTS: Of the original 119 patients,
      data were available for 117. Of the 117 patients, 97 had undergone primary
      pyeloplasty repair and 20 had undergone secondary pyleloplasty repair.
      Radiographic data were available for 84 patients with primary repair and 17
      patients with secondary repair. The radiographic success rate was 96.1% and
      94.1%, respectively. No statistically significant differences were found in the
      patient demographics, operative data, or postoperative or radiographic outcomes
      for the primary analysis. Additionally, no differences were found in the outcomes
      for patients with concomitant stone disease. CONCLUSION: These data represent the
      largest single-center report of its kind. These data strongly suggest that
      robotic-assisted laparoscopic pyeloplasty is a safe and durable option for
      secondary UPJO repair.

PMID- 22386424
TI  - Editorial comment.

PMID- 22386425
TI  - Partial segmental thrombosis of the corpus cavernosum: a case report and a review
      of the literature.
AB  - Partial segmental thrombosis of the corpus cavernosum (PSTCC) is a rare
      urological condition characterized by a painful, firm mass in the proximal part
      of the corpus cavernosum. The underlying pathophysiology of this condition is not
      fully understood. We present a case diagnosed by magnetic resonance imaging with
      complete clinical recovery after conservative treatment and novel associated
      findings, such as excessive alcohol intake. We also review the previous cases of
      PSTCC and propose a two hit model explaining PSTCC's etiology.

PMID- 22386426
TI  - Technique using a percutaneous nephroscope and nephroscopic scissors
      transurethrally for treatment of complicated orthotopic ureterocele in adult
      women.
AB  - OBJECTIVE: To present an endoscopic technique for the decompression of
      complicated orthotopic ureterocele in adult women. METHODS: Five women with
      complicated orthotopic ureterocele were evaluated in the present study. The
      ureterocele was complicated by stones in 2 patients and urinary tract infection
      in 4. An endoscopic technique was used for the treatment of these ureteroceles. A
      26F rigid nephroscope was placed into the bladder. When the ureterocele was seen
      in the bladder, the nephroscopic scissors was advanced through the nephroscopic
      channel to the ureterocele. A puncture was made on the anterior wall of the
      ureterocele using the nephroscopic scissors. Next, a ureteral catheter was
      introduced to puncture the ureterocele. Next, a window approximately 5-10 mm in
      diameter was opened on the wall of the ureterocele using the nephroscopic
      scissors. Finally, a double-J stent and urethral catheter were placed. The stones
      were fragmented using a pneumatic lithotripter. All the patients were evaluated
      with urinalysis, urine culture, ultrasonography, and voiding cystourethrography
      at the third month postoperatively. RESULTS: The mean procedure time was 18.4
      minutes. No complication was observed during the procedure, except for mild
      hematuria. The mean postoperative hospital stay was 19.8 hours. All patients with
      stones were stone free after the procedure. No cases of postoperative urinary
      tract infection developed. None of these patients had de novo reflux or
      obstruction at 3 months postoperatively. CONCLUSION: This technique could be an
      alternative treatment option for decompression of complicated orthotopic
      ureterocele in adult women.

PMID- 22386427
TI  - Open complete intrafascial nerve-sparing retropubic radical prostatectomy:
      technique and initial experience.
AB  - OBJECTIVE: To report our refinement of open intrafascial retropubic radical
      prostatectomy (OIF-RP) and 1-year follow-up results. PATIENTS AND METHODS: OIF-RP
      was performed in 231 cases of clinically localized Prostate cancer in a
      prospective study from January 2007 to December 2009. Inclusion criteria were
      good potency (IIEF-5 score >= 15), Gleason score <= 6, prostate-specific antigen
      (PSA) <= 10, and clinical T1-2 tumors. Endopelvic fascia was not incised, and the
      prostate capsule was freed laterally from surrounding fasciae and dorsally from
      Denonvillier's fascia, keeping all periprostatic fasciae/nerves intact.
      Functional outcomes were followed at 3 and 12 months (3 M and 12 M). Continence
      defined as complete (no pads), grade I (1-2 pads/day) and grade II (>2 pads/day).
      RESULTS: Median age was 63.3 years, body mass index 25.6, and PSA 5.4 ng/mL.
      Median operating time was 65 minutes (range 50-250), blood loss was 150 mL (range
      50-1000), preoperative IIEF-score was 23 (range 15-25). Pathologic stage was pT2
      (91%) and pT3 (9%). Gleason score was <= 6 (73%) and >= 7 (27%). Positive margins
      were 10% (pT2) and 65% (pT3). There were no postoperative
      complications/reinterventions. At 3 M, 60% of patients had full continence, and
      86% had full continence at 12 M (<= 60 years, 64% and 95% after 3 M and 12 M,
      respectively). At 3 M and 12 M, median IIEF-score was 14 (range 0-25) and 19
      (range 0-25), respectively. Baseline IIEF-score was reached by 50% (3 M) and 78%
      (12 M) (P<.001). IIEF-score was inversely correlated to patients' age (<= 60
      years 92%, 60-69 years 77%, >= 70 years 60%). CONCLUSION: OIF-RP follows
      rationales of radical prostatectomy and might be considered for selected
      patients. Preserving all periprostatic fasciae/nerves recuperates early
      continence and maintains potency without affecting oncological outcomes.

PMID- 22386428
TI  - Laparoscopic repair of inguinal cystocele using cystoscopic light test.
AB  - OBJECTIVE: To describe how the cystoscopic light test aids in the repair of
      inguinal bladder herniation. METHODS: After the diagnosis of a bladder herniation
      into the right inguinal canal using intravenous pyelography, laparoscopic repair
      was planned. A cystoscope was manipulated into the defect while turning off the
      laparoscopic light intra-abdominally. The light of the cystoscope could be
      identified through the cystocele, and the neck of the hernia was easily
      recognized. Once the bladder was reduced, the cystoscope was replaced, and
      reduction of the herniation was confirmed. RESULTS: We were able to successfully
      reduce the bladder herniation without recurrence at 24 months of follow-up.
      CONCLUSION: The cystoscopic light test represents a useful tool in the
      recognition of an inguinal bladder herniation, before, during, and after the
      definitive repair of the defect.

PMID- 22386429
TI  - An in vivo evaluation of a novel spiral cut flexible ureteral stent.
AB  - OBJECTIVE: The flow characteristics, ureteral conformance, and histopathologic
      changes of a novel spiral cut flexible ureteral stent (Percuflex Helical, Boston
      Scientific, Boston, MA) were evaluated in vivo in an acute and chronic porcine
      model. MATERIALS AND METHODS: Flow characteristics and ureteral conformance of
      the novel stent were determined in 6 acute and 6 chronic swine models and
      compared with a control ureteral stent (Percuflex Plus, Boston Scientific). The
      flow characteristics were determined in vivo after ligating the renal vessels and
      via a nephrostomy tube delivering a standard rate of 0.9% saline at 35 cm H(2)O.
      Flows in the unobstructed ureter, normal stent, intraluminally obstructed stent,
      extraluminal obstructed stent, and both intraluminally and extraluminally
      obstructed conditions were determined. In the chronic animals, flow was
      determined at day 10, with the stent in place and immediately after stent
      removal. Conformance and hydronephrosis was assessed on pyelograms.
      Histopathologic changes were also evaluated in the chronic animals. RESULTS: The
      acute and chronic flow characteristics in the novel stent were equivalent to the
      control stent. Size and weight of the kidney, degree of hydronephrosis, stent
      migration, and presence of urinary tract infection were also similar between the
      test and control stents. There were no differences seen in histopathologic
      grading or degree of encrustation in either stent. The novel stent appeared to
      conform better to the shape of the ureter in both acute and chronic animals.
      CONCLUSION: The novel helical stent appears to drain as well as a standard stent
      and causes no increased degree of histopathologic changes in the ureter.

PMID- 22386430
TI  - Editorial comment.

PMID- 22386431
TI  - Magnetic compression ostomy as new cystostomy technique in the rat:
      magnacystostomy.
AB  - OBJECTIVE: To report the first creation of magnetic compression cystostomy
      (magnacystostomy) using an easy and simple new technique in rats. Magnetic
      compression anastomoses (magnamosis) have been previously described for
      gastrointestinal, biliary, urinary, and vascular anastomoses. METHODS: Female
      rats were randomized into 2 groups (n = 10 each): a magnetic cystostomy group and
      a formal surgical cystostomy group as the control group. In the magnetic
      cystostomy group, a very small cylindrical magnet was inserted into the bladder.
      The external magnetic ball was placed subcutaneously into the suprapubic region,
      and the 2 magnets were coupled together strongly. On postoperative day 20 in the
      magnetic cystostomy group and day 10 in the surgical cystostomy group, the rats
      were killed, and the cystostomies were evaluated macroscopically,
      histopathologically, and by mechanical burst testing. RESULTS: In the surgical
      cystostomy group, 3 rats died. In the remaining rats, no evidence of
      complications was observed. However, mild adhesion in 1 rat in the magnetic
      cystostomy group and moderate adhesions in all the rats in the surgical
      cystostomy group were observed. No significant difference was found in burst
      pressure between the 2 groups (mean 162 mm Hg in the magnetic cystostomy group [n
      = 6] and 185 mm Hg in the surgical cystostomy [n = 5] group). However, the
      procedure time between the magnetic cystostomy group (7.70 +/- 1.64 minutes) and
      surgical cystostomy group (18.50 +/- 2.01 minutes) was significantly different (P
      < .001). CONCLUSION: Magnacystostomy is easy and safe in the rat model and could
      be useful for some suprapubic cystostomy procedures in humans.

PMID- 22386433
TI  - Re: Park et al.: Effect of the ratio of resected tissue in comparison with the
      prostate transitional zone volume on voiding function improvement after
      transurethral resection of prostate (Urology 2012;79:202-206).

PMID- 22386435
TI  - Re: Kim et al.: Testicular catch up growth: the impact of orchiopexy age (Urology
      2011;78:886-890).

PMID- 22386436
TI  - Re: Yu et al.: Simple, safe, and successful evacuation of severe organized clot
      retention using a catheter connected with wall suction: suction and fishing
      method (Urology 2011;78:1199-1202).

PMID- 22386437
TI  - Re: Shie et al.: Increased cell apoptosis of urothelium mediated by inflammation
      in interstitial cystitis/painful bladder syndrome (Urology 2012;79:484.e7
      484.e13).

PMID- 22386439
TI  - Encrusted cystitis.
AB  - We report a case of a patient who developed encrusted cystitis after
      transurethral resection of the prostate. This rare urological condition is
      characterized by intramucosal calcifications and is commonly preceded by
      urological instrumentation. Urea-splitting bacteria, most commonly
      Corynebacterium urealyticum, are the causative pathogen. Treatment is a
      combination of antibiotics, urine acidification, and endoscopic removal of
      encrustations.

PMID- 22386440
TI  - Left transperitoneal laparoendoscopic single-site radical nephrectomy in the
      presence of a duplicated inferior vena cava with associated complex renal
      vascular anomalies.
AB  - Laparo-endoscopic single-site (LESS) renal surgery is steadily gaining momentum.
      LESS by itself is technically challenging, with a potentially increased
      procedural risk, and the presence of major vascular anomaly may increase the risk
      of intraoperative mishap. Here we present a case of left transperitoneal LESS
      radical nephrectomy that was successfully performed in the presence of double
      inferior vena cava with associated complex renal vascular anomalies. What is more
      important is to bring such an aberrant vascular anatomy to the attention of
      laparoscopic, especially LESS, surgeons.

PMID- 22386441
TI  - Primary extragastrointestinal stromal tumor of the seminal vesicles.
AB  - Primary tumors originating from the seminal vesicles are extremely rare. We
      report a unique, previously unreported primary extragastrointestinal stromal
      tumor (EGIST) of the seminal vesicles in a 40-year-old man.

PMID- 22386442
TI  - Editorial comment.

PMID- 22386444
TI  - Determination of pig sex in meat and meat products using multiplex real time-PCR.
AB  - For specific production lines, European retail companies demand exclusively
      female pork meat. To control the quality of their suppliers the identification
      and a quantitative detection of the animal sex origin of the meat is therefore of
      importance for meat processors. To enable a fast and reliable detection of male
      pig meat, a real time-PCR-system was designed in the present study. This was
      based on the genes AMEL-X and AMEL-Y. The real time-PCR assay allowed the
      detection of male pig meat at a concentration of 1% yielding a detection
      probability of 100% while the detection probability investigating meat samples
      containing 0.1% male pig meat was 44.4%. The analytic sensitivity of this system
      was assessed to be <5 pg DNA per PCR reaction. The assessment of the accuracy of
      the real time-PCR assay to correctly identify sex individuals was investigated
      with 62 pigs including males (n=29) and females (n=33) belonging to different
      breeds/lines. With the newly designed test all analysed animals were correctly
      sexed. No amplification was obtained with cow, goat, sheep, turkey and chicken
      genomic DNA. The presented assay can be used for sex diagnosis, for the detection
      of male pig meat and for meat quality control.

PMID- 22386446
TI  - Ruling out HIV infection when testing for severe combined immunodeficiency and
      other T-cell deficiencies.

PMID- 22386447
TI  - Extreme challenges and advances in archaeal proteomics.
AB  - Archaea display amazing physiological properties that are of interest to
      understand at the molecular level including the ability to thrive at extreme
      environmental conditions, the presence of novel metabolic pathways (e.g.
      methanogenesis, methylaspartate cycle) and the use of eukaryotic-like protein
      machineries for basic cellular functions. Coupling traditional genetic and
      biochemical approaches with advanced technologies, such as genomics and
      proteomics, provides an avenue for scientists to discover new aspects related to
      the molecular physiology of archaea. This review emphasizes the unusual
      properties of archaeal proteomes and how high-throughput and specialized mass
      spectrometry-based proteomic studies have provided insight into the molecular
      properties of archaeal cells.

PMID- 22386448
TI  - Low vitamin D levels are associated with increased rejection and infections after
      lung transplantation.
AB  - BACKGROUND: The prevalence of vitamin D deficiency in lung disease is greater
      than in the general population. Vitamin D deficiency may negatively affect immune
      and lung function. Accordingly, we hypothesized that lung transplant recipients
      with vitamin D deficiency are more susceptible to rejection and infections after
      transplantation. METHODS: Transplant outcomes were reviewed in a retrospective
      cohort of 102 lung transplant recipients who had 25-hydroxyvitamin D [25(OH)D]
      levels drawn during the near-transplant period (100 days pre- or post
      transplant). RESULTS: In the near-transplant period, 80% of recipients were
      25(OH)D-deficient and 20% were not 25(OH)D-deficient. Episodes of acute cellular
      rejection in the deficient group were more frequent than in the non-deficient
      group [mean 1.27 (0.99 to 1.55) vs 0.52 (0.12 to 0.93), p = 0.006]. The rejection
      rate in the deficient group was more than double that of the the non-deficient
      group [IRR 2.43 (1.30 to 4.52), p = 0.005]. Infectious episodes were also more
      frequent in the deficient group than in the non-deficient group [mean 4.01 (3.24
      to 4.79) vs 2.71 (1.47 to 3.96), p = 0.04]. The mortality rate of recipients who
      remained 25(OH)D-deficient 1 year after transplant was almost 5-fold higher than
      in recipients who were not 25(OH)D-deficient [IRR 4.79 (1.06 to 21.63), p =
      0.04]. CONCLUSIONS: Low serum 25(OH)D levels in lung transplant recipients were
      associated with increased incidence of acute rejection and infection. The
      mortality of recipients who remained deficient 1 year post-transplant was higher
      than that of recipients who maintained normal vitamin D levels at 1 year post
      transplant.

PMID- 22386449
TI  - Editorial Commentary: Determining the cost-effectiveness of mechanical
      circulatory support.

PMID- 22386450
TI  - beta-adrenergic agonist infusion during extracorporeal lung perfusion: effects on
      glucose concentration in the perfusion fluid and on lung function.
AB  - BACKGROUND: We recently showed in a pig model of ex vivo lung perfusion (EVLP)
      that lung edema correlates with glucose consumption. We investigated whether
      salbutamol, a beta-adrenergic receptor agonist known to upregulate fluid
      transport in the lung, modulates glucose concentration in the perfusate during
      EVLP. METHODS: Lungs from domestic pigs underwent normothermic EVLP. At the end
      of controlled reperfusion, lungs were ventilated and perfused for 60 minutes,
      then randomized to salbutamol (beta-Agonist) infusion or placebo (Control) for
      180 minutes. Functional parameters were assessed. RESULTS: In the beta-Agonist
      group, glucose concentration decreased over time more than corresponding Control
      values (analysis of variance [ANOVA], p = 0.05). Mean pulmonary artery pressure
      (mPAP) was 16 +/- 1 mm Hg in the beta-Agonist group vs 21 +/- 1 mm Hg in the
      Controls (ANOVA p < 0.05). Baseline mPAP was correlated with the drop of mPAP
      after the beta-agonist infusion (R(2) = 0.856, p < 0.05). Dynamic compliance
      dropped from 51 +/- 10 to 31 +/- 6 ml/cm H(2)O in the beta-Agonist group and from
      60 +/- 4 to 21 +/- 3 ml/cm H(2)O in the Control group (ANOVA, p < 0.05 beta
      agonist vs Control). The Delta partial pressure of oxygen/fraction of inspired
      oxygen was 418 +/- 15 and 393 +/- 12 mm Hg in the beta-Agonist and Control
      groups, respectively (t-test p = 0.106). CONCLUSIONS: Glucose concentration in
      the perfusate was affected by salbutamol. Salbutamol was associated with lower
      pulmonary pressures and better lung mechanics. These data suggest a possible role
      for salbutamol as a pharmacologic adjunct during EVLP before transplantation.

PMID- 22386451
TI  - Association of pre-operative interleukin-6 levels with Interagency Registry for
      Mechanically Assisted Circulatory Support profiles and intensive care unit stay
      in left ventricular assist device patients.
AB  - BACKGROUND: Inflammatory mechanisms are associated with worse prognosis in end
      stage heart failure (ESHF) patients who require left ventricular assist device
      (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory
      Support (INTERMACS) profiles describe patient condition at pre-implant and
      outcome. This study assessed the relationship among inflammation patterns and
      INTERMACS profiles in LVAD recipients. METHOD: Thirty ESHF patients undergoing
      LVAD implantation as bridge to transplant were enrolled. Blood and urine samples
      were collected pre-operatively and serially up to 2 weeks post-operatively for
      assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL
      10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine
      neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function
      was evaluated by the total sequential organ failure assessment (tSOFA) score.
      Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive
      care unit (ICU) length of stay. RESULTS: Fifteen patients had INTERMACS profiles
      1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6
      levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD
      implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group
      A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA
      score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6
      levels. CONCLUSIONS: The INTERMACS profiles reflect the severity of the pre
      operative inflammatory activation and the post-implant inflammatory response,
      affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may
      contribute to poor outcome in patients with severe INTERMACS profile.

PMID- 22386452
TI  - The cross-cultural significance of control and autonomy in parent-adolescent
      relationships.

PMID- 22386454
TI  - Toxicity of the fungicide trifloxystrobin on tadpoles and its effect on fish
      tadpole interaction.
AB  - Contamination of aquatic systems is a major environmental stress that can
      interfere with predator-prey interactions, altering prey or predator behavior
      differentially. We determined toxicity parameters of the fungicide
      trifloxystrobin (TFS) and examined its effects on predation rate, using a fish
      predator (Synbranchus marmoratus) and four anuran tadpole species as prey
      (Rhinella arenarum, Physalaemus santafecinus, Leptodactylus latrans, and
      Elachistocleis bicolor). TFS was not equally toxic to the four tadpole species,
      E. bicolor being the most sensitive species, followed by P. santafecinus, R.
      arenarum, and L. latrans. Predation rates were evaluated using different
      treatments that combined predator and prey exposed or not to this fungicide. TFS
      would alter the outcome of eel-tadpole interaction by reducing prey movements;
      thus, prey detection would decrease and therefore tadpole survival would
      increase. In addition, eels preyed selectively upon non-exposed tadpoles avoiding
      the exposed ones almost all throughout the period evaluated. Predation rate
      differed among prey species; such differences were not due to TFS exposure, but
      to interspecific differences in behavior. The mechanism that would explain TFS
      induced reduction in predation rates remains unclear; however, what is clear is
      that sublethal TFS concentrations have the potential to alter prey behavior,
      thereby indirectly altering predator-prey interactions. In addition, we consider
      that predator-prey relationships are measurable responses of toxicant exposure
      and provide ecological insight into how contaminants modify predator-prey
      interactions.

PMID- 22386453
TI  - A magnetization transfer imaging study of corpus callosum myelination in young
      children with autism.
AB  - BACKGROUND: Several lines of evidence suggest that autism may be associated with
      abnormalities in white matter development. However, inconsistencies remain in the
      literature regarding the nature and extent of these abnormalities, partly because
      of the limited types of measurements that have been used. Here, we used
      magnetization transfer imaging to provide insight into the myelination of the
      corpus callosum in children with autism. METHODS: Magnetization transfer imaging
      scans were obtained in 101 children with autism and 35 typically developing
      children who did not significantly differ with regard to gender or age. The
      midsagittal area of the corpus callosum was manually traced and the magnetization
      transfer ratio (MTR) was calculated for each voxel within the corpus callosum.
      Mean MTR and height and location of the MTR histogram peak were analyzed.
      RESULTS: Mean MTR and MTR histogram peak height and location were significantly
      higher in children with autism than in typically developing children, suggesting
      abnormal myelination of the corpus callosum in autism. CONCLUSIONS: The
      differences in callosal myelination suggested by these results may reflect an
      alteration in the normally well-regulated process of myelination of the brain,
      with broad implications for neuropathology, diagnosis, and treatment of autism.

PMID- 22386455
TI  - The chemical and environmental property space of REACH chemicals.
AB  - The European regulation on chemicals, REACH (Registration, Evaluation,
      Authorisation and Restriction of Chemicals), came into force on 1 June 2007. With
      pre-registration complete in 2008, data for these substances may provide an
      overview of the expected chemical space and its characteristics. In this paper,
      using various in silico computation tools, we evaluate 48782 neutral organic
      compounds from the list to identify hazardous and safe compounds. Two different
      classification schemes (modified Verhaar and ECOSAR) identified between 17% and
      25% of the compounds as expressing only baseline toxicity (narcosis). A smaller
      portion could be identified as reactive (19%) or specifically acting (2.7%),
      while the majority were non-assigned (61%). Overall environmental persistence,
      bioaccumulation and long-range transport potential were evaluated using structure
      activity relationships and a multimedia fugacity-based model. A surprisingly high
      proportion of compounds (20%), mainly aromatic and halogenated, had a very high
      estimated persistence (>195 d). The proportion of compounds with a very high
      estimated bioconcentration or bioaccumulation factor (>5000) was substantially
      less (6.9%). Finally, a list was compiled of those compounds within the
      applicability domain of the models used, meeting both persistence and
      bioaccumulation criteria, and with a long-range transport potential comparable to
      PCB. This list of 68 potential persistent organic pollutants contained many well
      known compounds (all halogenated), but notably also five fluorinated compounds
      that were not included in the EINECS inventory. This study demonstrates the
      usability of in silico tools for identification of potentially environmentally
      hazardous chemicals.

PMID- 22386456
TI  - Estimation of thyroid doses and health risks resulting from the intake of
      radioactive iodine in foods and drinking water by the citizens of Tokyo after the
      Fukushima nuclear accident.
AB  - The release of radioactive materials from the Fukushima nuclear power plant after
      the Great East Japan Earthquake on 11 March 2011 poses health risks. In this
      study, the intake of iodine 131 (I-131) in drinking water and foods (milk, dairy
      products, and vegetables) by citizens of Tokyo was estimated. The effects of
      countermeasures (restrictions on the distribution of foods and the distribution
      of bottled water for infants) on reducing intake were also evaluated. The average
      thyroid equivalent doses without countermeasures from 21 March 2011 were 0.42 mSv
      in adults, 1.49 mSv in children, and 2.08 mSv in infants. Those with
      countermeasures were 0.28, 0.97, and 1.14 mSv respectively, reductions of 33%,
      35%, and 45%. Drinking water contributed more to intake by adults and children
      than foods. The intake of I-131 within the first 2 weeks was more than 80% of the
      estimated intake, owing to its short half-life, indicating that rapid
      countermeasures are important in reducing intake. The average risks of cancer
      incidence and mortality due to I-131 for infants were estimated to be 3*10(-5)
      and 0.2*10(-5), respectively, lower than the annual risks of traffic accidents,
      naturally occurring radioactive material (potassium 40), and environmental
      pollutants such as diesel exhaust particles.

PMID- 22386457
TI  - SMX degradation by ozonation and UV radiation: a kinetic study.
AB  - The rate constants of sulfamethoxazole (SMX) degradation by ozonation and UV(254)
      radiation were investigated under various parameters including influent ozone gas
      concentration, initial SMX concentration, UV light intensity, ionic strength,
      water quality in terms of varying anions (bicarbonate, sulfate and nitrate),
      humic acid (HA) and pH. The results indicated that the removal of SMX by
      ozonation and UV(254) radiation fitted well to a pseudo first-order kinetic model
      and the rate constants were in the range of (0.9-9.8)*10(-3) and (1.7-18.9)*10(
      3) s(-1), respectively. The second-order rate constants of SMX with ozone
      (ko(3)), under varying operational parameters, were also determined and varied in
      the range of (0.60-3.38)+/-0.13*10(5)M(-1) s(-1). In addition, SMX degradation
      through UV pretreatment followed by ozonation in the presence of HA was proved to
      be an effective method which can remove SMX with a low ozone dose. The results
      suggested that ozonation of SMX was more affected by concentration of influent
      ozone gas, alkalinity, and HA, while incident UV light intensity, pH, and HA were
      the dominant factors influencing UV degradation of SMX.

PMID- 22386458
TI  - Photocatalytic removal of organic pollutants in aqueous solution by
      Bi(4)Nb(x)Ta((1-x))O(8)I.
AB  - In this work, Bi(4)Nb(x)Ta((1-x))O(8)I photocatalysts have been synthesized by
      solid state reaction method and characterized by powder X-ray diffraction,
      scanning electron microscope and UV-Vis near infrared diffuse reflectance
      spectroscopy. The photocatalytic activity of these photocatalysts was evaluated
      by the degradation of methyl orange (MO) in aqueous solutions under visible
      light, UV light and solar irradiation. The effects of catalyst dosage, initial pH
      and MO concentration on the removal efficiency were studied, and the
      photocatalytic reaction kinetics of MO degradation as well. The results indicated
      that Bi(4)Nb(x)Ta((1-x))O(8)I exhibited high photocatalytic activity for the
      removal of MO in aqueous solutions. For example, the removal efficiency of MO by
      Bi(4)Nb(0.1)Ta(0.9)O(8)I was as high as 92% within 12 h visible light irradiation
      under the optimal conditions: initial MO concentration of 5-10 mg L(-1), catalyst
      dosage of 6 g L(-1) and natural pH (6-8), the MO molecules could be completely
      degradated by Bi(4)Nb(0.1)Ta(0.9)O(8)I within 40 min under UV light irradiation,
      and the photodegradation efficiency reaches to 60% after 7 h solar irradiation.
      Furthermore, the photocatalytic degradation of Bisphenol A (BPA) was also
      investigated under visible light irradiation. It is found that 99% BPA could be
      mineralized by Bi(4)Nb(0.1)Ta(0.9)O(8)I after 16 h visible light irradiation.
      Through HPLC/MS, BOD, TOC, UV-Vis measurements, we determined possible
      degradation products of MO and BPA. The results indicated that MO was degradated
      into products which are easier to be biodegradable and innocuous treated, and BPA
      could be mineralized completely. Furthermore, the possibility for the
      photosensitization effect in the degradation process of MO under visible light
      irradiation has been excluded.

PMID- 22386459
TI  - Biodegradation of multiple cyanobacterial metabolites in drinking water supplies.
AB  - The fate of multiple cyanobacterial metabolites was assessed in two Australian
      source waters. The saxitoxins were the only metabolites shown to be non
      biodegradable in Myponga Reservoir water, while microcystin-LR (MCLR) and geosmin
      were biodegradable in this water source. Likewise, cylindrospermopsin (CYN) was
      shown to be biodegradable in River Murray water. The order of ease of
      biodegradability followed the trend: MCLR>CYN>geosmin>saxitoxins. Biodegradation
      of the metabolites was affected by temperature and seasonal variations with more
      rapid degradation at 24 degrees C and during autumn compared with 14 degrees C
      and during winter. A microcystin-degrading bacterium was isolated and shown to
      degrade four microcystin variants within 4 h. This bacterium, designated as TT25,
      was shown to be 99% similar to a Sphingopyxis sp. based on a 16S rRNA gene
      fragment. Isolate TT25 was shown to contain a homologue of the mlrA gene; the
      sequence of which was 99% similar to that of a previously reported microcystin
      degrader. Furthermore, isolate TT25 could degrade the microcystins in the
      presence of copper sulphate (0.5 mg L(-1) as Cu(2+)) which is advantageous for
      water authorities dosing such algicides into water bodies to control
      cyanobacterial blooms.

PMID- 22386460
TI  - Relative bioavailability to laying hens of indicator polychlorobiphenyls present
      in soil.
AB  - Transfer of indicator polychlorobiphenyls (PCBs) from soil into hen eggs may
      occur in hens reared outdoor, which ingest significant amounts of soil. This
      transfer depends on the bioavailability of the ingested compounds. The impact of
      soil on the bioavailability of indicator PCBs was assessed by means by a relative
      bioavailability (RBA) trial, in which their deposition in egg yolk and in
      abdominal fat, in response to their ingestion through contaminated-soil and
      through spiked-oil were compared. A sandy soil (709 MUg indicator PCBs kg(-1) dry
      matter) was collected in the vicinity of a former fire involving treated wood.
      Twenty-eight laying hens were individually housed and fed one of the seven
      experimental diets during 14 d. The seven experimental diets were an
      uncontaminated control diet, three diets in which contaminated soil was
      introduced at levels of 3%, 6% and 9% and three diets in which spiked oil was
      introduced to achieve similar levels and profile of contaminants. Yolk, abdominal
      fat and liver were collected at the end of exposure. Indicator PCBs were
      extracted by ASE (Accelerated Solvent Extraction) and analyzed by GC-HMRS. Within
      each ingested matrix, the concentration of indicator PCBs in yolk and in
      abdominal fat linearly increased with the amount of indicator PCB ingested
      (P<0.001). Except for PCB 28, the slopes of the responses to soil and to oil
      could not be differentiated (P>0.1). RBA estimates did not differ from 1 for all
      indicator PCBs except for PCB 28, for which it was 0.58-0.59. Measurements
      performed on liver confirm these conclusions.

PMID- 22386461
TI  - Polyaniline nanofibers: acute toxicity and teratogenic effect on Rhinella
      arenarum embryos.
AB  - The fate and effect of nanomaterials in the environment is of paramount
      importance towards the technological application of the materials. This work
      shows the ecotoxicological potential of polyaniline (PANI) nanofibers in the
      larvae Rhinella arenarum by means of AMPHITOX test. Acute toxicity of PANI
      nanofibers towards embryos of the common South American toad R. arenarum (Anura:
      bufonidae) was evaluated in the premetamorphosis (stage 25) larvae. The exposure
      of R. arenarum larvae to at dose of 150, 250 and 400 mg L(-1) resulted in 100%
      viability within 96 h exposure. The embryos at 2-4 blastomers stage (early life
      stage teratogenic test) revealed that embryos were not killed and no teratogenic
      effects were observed when embryos were incubated with PANI nanofibers (150 and
      250 mg L(-1)), while only a growth retardation of embryos was induced at levels
      of 250 mg PANI nanofibers L(-1). On the other hand, at 400 mg L(-1)
      concentration, a reduction in the body length of larvae and tail malformation was
      observed. This results suggest that a concentration-dependent toxicity is
      operative, typified by phenotypes that had abnormal body axes. The presence of
      PANI nanofibers in gut contents and its excretion by larval stages of R. arenarum
      was confirmed by UV-visible spectroscopy.

PMID- 22386462
TI  - Electrokinetic remediation of organochlorines in soil: enhancement techniques and
      integration with other remediation technologies.
AB  - Electrokinetic remediation has been increasingly used in soils and other matrices
      for numerous contaminants such as inorganic, organic, radionuclides, explosives
      and their mixtures. Several strategies were tested to improve this technology
      effectiveness, namely techniques to solubilize contaminants, control soil pH and
      also couple electrokinetics with other remediation technologies. This review
      focus in the experimental work carried out in organochlorines soil
      electroremediation, aiming to systemize useful information to researchers in this
      field. It is not possible to clearly state what technique is the best, since
      experimental approaches and targeted contaminants are different. Further research
      is needed in the application of some of the reviewed techniques. Also a number of
      technical and environmental issues will require evaluation for full-scale
      application. Removal efficiencies reported in real contaminated soils are much
      lower than the ones obtained with spiked kaolinite, showing the influence of
      other factors like aging of the contamination and adsorption to soil particles,
      resulting in important challenges when transferring technologies into the field.

PMID- 22386463
TI  - In vivo and in vitro metabolism of tobacco-specific nitrosamine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by the freshwater planarian,
      Dugesia japonica.
AB  - Cigarette smoke is a risk factor for human health, and many studies were
      conducted to investigate its adverse effects on humans and other mammals.
      However, since large amounts of cigarette products are produced and consumed, it
      is possible that tobacco chemicals can end up in aquatic environments through
      several routes, thus influencing aquatic organisms. In this study, the presence
      of tobacco-specific nitrosamine (TSNA), 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK), in aquatic environment was demonstrated. Since toxic effects on
      and distribution patterns of tobacco chemicals in aquatic organisms were rarely
      studied, after results of an acute toxicity pretest were obtained, experiment was
      conducted to investigate the bioaccumulation pattern of NNK and distribution
      patterns of its metabolites, mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL), in NNK-treated freshwater planarians, Dugesia japonica. Results from in
      vivo and in vitro studies showed that NNK was readily converted to NNAL through
      the carbonyl reduction in bodies of NNK-treated planarians. Tissue concentrations
      of both chemicals increased in time- and dose-dependent manners. Furthermore, we
      examined the end products of NNK/NNAL alpha-hydroxylation in NNK-treated
      planarians, but only 1-(3-pyridyl)-1,4-butanediol was detected, suggesting that
      NNK metabolism in planarians partially differs from that in mammalian systems.
      This is the first report on NNK metabolism in an aquatic organism and can be used
      as a foundation for developing freshwater planarians as a new in vivo model for
      the study of NNK toxicology in the future.

PMID- 22386464
TI  - Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in
      office dust using high resolution gas chromatography-mass spectrometry.
AB  - The study focused on analysis of polybromobiphenyls (PBBs) and polybromodiphenyl
      ethers (PBDEs) congeners in office dust obtained in Pretoria, South Africa. Of
      the 32 congeners considered for identification, (BB-1, 2, 4, 10, 15, 26, 29, 30,
      31, 38, 49, 80, 103, 153, 155, 209 and BDE-3, 15, 17, 28, 47, 66, 77, 85, 99,
      100, 126, 138, 153, 154, 183, 209) only BB-2, 4, 30, 153, 209 and BDE-47, 66, 85,
      99, 153 and 209 congeners were detected. The sum of PBBs concentration detected
      in office dust ranged from <dl-196 ng g(-1) dry weight (dw) with a median and
      mean of 11.4 and 38.2 ng g(-1), respectively. On the other hand, the sum of PBDEs
      concentration detected ranged from 21.6 to 578.6 ng g(-1)dw with a median and
      mean of 162 and 169 ng g(-1)dw, respectively. A Spearman rank correlation between
      ?(5)PBBs and ?(6)PBDEs (r(s)=0.55, p=0.003), indicated a statistical significant
      positive correlation for the similarity of pollution sources for both compound
      classes. However, no correlation was observed between the number of electronic
      materials and summation of concentrations of PBBs and PBDEs congeners detected.
      Concentrations of PBDEs detected in this study are substantially lower than
      reported in office dust in developed countries.

PMID- 22386465
TI  - Effects of inorganic carbon concentration on carbon formation, nitrate
      utilization, biomass and oil accumulation of Nannochloropsis oculata CS 179.
AB  - This investigation examined the effects of the inorganic carbon concentration (4,
      0.8 and 0 g/L NaHCO(3)) on the carbon formation, nitrate utilization, growth and
      fatty acids compositions of Nannochloropsis oculata. The dissolved inorganic
      carbon (DIC) concentration in the three treatments decreased sharply during the
      first 6 days, and the percentage of dissolved organic carbon (DOC) (% of total
      organic carbon (TOC)) decreased with the depletion of the DIC. The NO(3)(-)
      assimilation of the algae was correlated with the DIC concentration. The algae in
      the highest DIC treatment had the highest specific grow rate (0.0843 d(-1))
      (P<0.0001), and their biomass and fatty acid methyl esters (FAME) productivity
      were 84.00 and 9.69 mg/L/d, respectively (P<0.0001). Contents of C16 and C18
      series (% of FAME) were high and the C16:0 increased with the decrease of C18:1
      during the cultivation. The iodine value (IV) of the algae was low at the low DIC
      media.

PMID- 22386466
TI  - Mesoporous activated carbon from wood sawdust by K2CO3 activation using microwave
      heating.
AB  - Wood sawdust was converted into a high-quality activated carbon (WSAC) via
      microwave-induced K(2)CO(3) activation. The operational variables including
      chemical impregnation ratio, microwave power and irradiation time on the carbon
      yield and adsorption capability were identified. The surface physical
      characteristics of WSAC were examined by pore structural analysis, scanning
      electron microscopy and nitrogen adsorption isotherms. The adsorptive behavior of
      WSAC was quantified using methylene blue as model dye compound. The best
      conditions resulted in activated carbon with a monolayer adsorption capacity of
      423.17 mg/g and carbon yield of 80.75%. The BET surface area, Langmuir surface
      area and total pore volume were corresponded to 1496.05 m(2)/g, 2245.53 m(2)/g
      and 0.864 cm(3)/g, respectively. The findings support the potential to prepare
      high surface area and mesoporous activated carbon from wood sawdust by microwave
      assisted chemical activation.

PMID- 22386467
TI  - Use of dry-milling derived thin stillage for producing eicosapentaenoic acid
      (EPA) by the fungus Pythium irregulare.
AB  - This study was to explore the use of thin stillage, a major byproduct in dry
      milling corn-ethanol plants, for production of eicosapentaenoic acid (EPA) by the
      fungus Pythium irregulare. Thin stillage contains various compounds that were
      ideal for fungal growth. Thin stillage concentration and temperature played
      important roles in fungal growth and EPA production. When 50% thin stillage was
      used in a stepwise temperature shift culture process, the cell density reached 23
      g/L at day 9 with EPA yield and productivity of 243 and 27 mg/L day,
      respectively. The fungal biomass contained 39% lipid, 28% protein, 30%
      carbohydrate, and 3% ash. The fungal culture also generated a nutrient-depleted
      liquid by removing organic compounds in the raw thin stillage. The results
      collectively showed a new use of thin stillage by feeding to the fungus P.
      irregulare for producing omega-3 fatty acids.

PMID- 22386468
TI  - Biorefinery of olive pruning using various processes.
AB  - Biorefinery developed involve separation of olive pruning into two parts: main
      (OPM) (stems>1cm diameter), and residual (OPR) (stems<1cm diameter, and leaves).
      OPM was submitted to hydrothermal treatment, separating: a liquid fraction (HL),
      rich in products of hemicelluloses decomposition, and other solid (HS), rich in
      cellulose and lignin. HS is subject to pulping, resulting: a liquid fraction
      (HPL), rich in lignin, and other solid (HPS), rich in cellulose. Up to 42% of the
      polysaccharides from OPM were recovered in HL as valuable compounds. HPS can be
      used for the bioethanol production by saccharification and fermentation, reaching
      a bioethanol conversion of 90.6% of the theoretical value. In addition, HPS
      obtained paper with lower strength properties than those of paper obtained from
      OPM pulp directly. OPR provided 18.70 MkJ/t heating values, 1094-2234 degrees C
      flame temperature, and 45-53 degrees C dew point temperature, with a cost of the
      unit of heat (3.20 ?/MkJ) much lower than fossil fuels fluids.

PMID- 22386469
TI  - Total solids content drives high solid anaerobic digestion via mass transfer
      limitation.
AB  - The role of the total solids (TS) content on anaerobic digestion was investigated
      in batch reactors. A range of TS contents from 10% to 35% was evaluated, four
      replicates were performed. The total methane production slightly decreased with
      TS concentrations increasing from 10% to 25% TS. Two behaviors were observed at
      30% TS: two replicates had similar performances to that at 25% TS; for the two
      other replicates, the methane production was inhibited as observed at 35% TS.
      This difference suggested that 30% TS content corresponded to a threshold of the
      solids content, above which methanogenesis was strongly inhibited. The Anaerobic
      Digestion Model No. 1 (ADM1) was used to describe the experimental data. The
      effects of hydrolysis step and liquid/gas mass transfer were particularly
      investigated. The simulations showed that mass transfer limitation could explain
      the low methane production at high TS, and that hydrolysis rate constants
      slightly decreased with increasing TS.

PMID- 22386470
TI  - Femoral nerve entrapment after high energy knee trauma.

PMID- 22386472
TI  - Efficacy and safety of the alpha4beta2 neuronal nicotinic receptor agonist ABT
      894 in patients with diabetic peripheral neuropathic pain.
AB  - Preclinical and clinical studies suggest that neuronal nicotinic receptor (NNR)
      agonists may be a novel and effective therapy for numerous painful conditions.
      Analgesic efficacy and safety of the highly selective alpha(4)beta(2) NNR agonist
      ABT-894 was evaluated in 2 separate randomized, double-blind, multicenter,
      placebo-controlled clinical trials in patients with diabetic peripheral
      neuropathic pain (DPNP). Study 1 (280 patients randomized) tested 1, 2, and 4 mg
      ABT-894 twice daily compared with placebo and 60 mg duloxetine once per day over
      8 weeks of treatment. Study 2 (124 patients randomized) tested 6 mg ABT-894 twice
      daily vs placebo for 8 weeks. The primary efficacy outcome measure in both
      studies was the weekly mean of the 24-hour average pain score recorded in each
      patient's diary. In both trials, none of the ABT-894 dose groups showed efficacy
      compared with placebo, whereas duloxetine achieved a statistically significant
      improvement over placebo in Study 1. All dose levels of ABT-894 were well
      tolerated, and no significant safety issues were identified. These results are in
      contrast to the outcome of a previously reported study of DPNP using the less
      selective alpha(4)beta(2) NNR agonist ABT-594, which demonstrated efficacy
      compared with placebo, albeit with significant tolerability limitations. The
      failure of the highly selective alpha(4)beta(2) NNR agonist ABT-894 indicates
      that it may not be possible to define a therapeutic index for this mechanism or
      that selectively targeting alpha(4)beta(2) NNRs may not be a viable approach to
      treating neuropathic pain.

PMID- 22386473
TI  - Demographic and medical parameters in the development of complex regional pain
      syndrome type 1 (CRPS1): prospective study on 596 patients with a fracture.
AB  - Limited data are available on the incidence of complex regional pain syndrome
      type 1 (CRPS1) and on demographic and medical risk factors for the development of
      CRPS1. The objective of this study was to investigate the incidence of CRPS1 in
      patients with a fracture using 3 sets of diagnostic criteria and to evaluate the
      association between demographic/medical factors and the development of CRPS1
      diagnosed with the Harden and Bruehl criteria. A prospective multicenter cohort
      study of 596 patients (ages 18 years and older) with a single fracture of the
      wrist, scaphoid, ankle, or metatarsal V, recruited patients from the emergency
      rooms of 3 Dutch hospitals. Of the 596 participants, 42 (7.0%) were diagnosed
      with CRPS1 according to the Harden and Bruehl criteria, 289 (48.5%) according to
      the International Association for the Study of Pain criteria, and 127 (21.3%)
      according to the criteria of Veldman. An analysis of the medical and demographic
      differences revealed that patients in whom CRPS1 later developed more often had
      intra-articular fractures, fracture dislocations, rheumatoid arthritis, or
      musculoskeletal comorbidities. An ankle fracture, dislocation, and an intra
      articular fracture contributed significantly to the prediction of the development
      of CRPS1. No CRPS1 patients were symptom free at 12 months (T3). At baseline,
      patients with CRPS1 had significantly more pain than patients without CRPS1
      (P<.001). The incidence of the diagnosis of CRPS1 after a single fracture depends
      to a large extent on the diagnostic criteria used. After a fracture, 7% of the
      patients developed CRPS1 and none of the patients were free of symptoms at 1-year
      follow-up.

PMID- 22386471
TI  - Pain, affective symptoms, and cognitive deficits in patients with cerebral
      dopamine dysfunction.
AB  - Converging preclinical, and human epidemiological, neuroimaging, and genetic
      evidence suggests a central role for dopamine neurotransmission in modulating
      pain perception and analgesia. Dysregulation in dopamine signaling may modulate
      the experience of pain both directly, by enhancing or diminishing the propagation
      of nociceptive signals, and indirectly, by influencing affective and cognitive
      processes, which affect the expectation, experience, and interpretation of
      nociceptive signals. Hypersensitivity to pain and high rates of comorbid chronic
      pain are common in disorders linked with deficits in dopamine system function,
      including disorders of mood and affect, substance abuse, and Parkinson disease.
      Hyposensitivity to pain, however, is common in patients with schizophrenia, which
      has been linked with excessive dopamine neurotransmission. Although patients are
      typically affected most by the primary symptoms of their disorders, alterations
      in pain perception may further increase the burden of their illness, compromising
      their quality of life. The present review focuses on this relationship, and
      discusses clinical and potential therapeutic implications for both patients with
      dopamine-related disorders and those with chronic pain syndromes.

PMID- 22386474
TI  - Evidence for analgesic effect in acute pain - 50 years on.

PMID- 22386475
TI  - The effect of changes in lower limb pain on the rate of progression of locomotor
      disability in middle and old age: evidence from the NorStOP cohort with 6-year
      follow-up.
AB  - Locomotor disability (LMD) is common at older ages, and can lead to other
      significant disability and mortality. Prevalent pain has been shown to be
      associated with LMD. This article aimed to assess the association between changes
      in lower limb pain status (ascertained from a manikin) and changes in the level
      of self-reported LMD in a sample of UK adults age >= 50years, over a 6-year
      period (data collected at 3-year intervals). There was an average increase in the
      level of LMD over 6 years. Reports of an onset of lower limb pain were associated
      with a relative increase in LMD, independently of sociodemographic factors and
      the onset of selected comorbid diseases. A dose-response relationship was
      observed between the onset of multiple lower limb joint involvement and more
      frequent or intense pain and larger increases in LMD. Becoming free from lower
      limb pain was associated with a relative decrease in LMD, but did not return LMD
      scores to the level of those who had remained pain-free throughout. This is
      consistent with a cumulative effect on LMD of recurrent episodes of pain. Lower
      limb pain may be a key target for prevention and rehabilitation to reduce years
      lived with disability in later life.

PMID- 22386476
TI  - Ibn Imran's 10th century Treatise on Melancholy.
AB  - Some see current views of mental illness, such as depression, as merely
      contemporary social constructions, with madness seen as a modernist break from
      medieval and ancient concepts. In contrast to these assumptions, here we describe
      one of the earliest texts on melancholia and mania, by Ibn Imran, an Arab
      physician of the 10th century.

PMID- 22386477
TI  - Electrophysiological characteristics in four patients from Brazil with stiff
      person syndrome.
AB  - Stiff person syndrome (SPS) is a rare immune-mediated disorder of the central
      nervous system characterized by muscle rigidity and episodic muscle spasms. The
      diagnosis of SPS is based on electrophysiological studies. We analyzed the
      electrophysiological features in four patients from Brazil who fulfilled the
      clinical criteria for SPS. The most common electrophysiological abnormalities
      were continuous motor unit activity, co-contracting, and the presence of the
      cutaneomuscular reflex. Despite all patients having clinical characteristics of
      SPS during the disease, no patient met all the electrophysiological criteria for
      SPS even after repeat electrophysiological studies. This shows that a diagnosis
      of SPS should not be restricted to patients with all the classic
      electrophysiological changes but should be considered in the presence of one or
      some of those changes.

PMID- 22386478
TI  - Fibrinogen polymorphisms associated with sporadic cerebral hemorrhage in a
      Chinese population.
AB  - Fibrinogen plays an important role in the intrinsic and extrinsic pathways of
      blood coagulation. This study investigated the association between common
      variants in the fibrinogen gene and the risk of developing sporadic cerebral
      hemorrhage (CH). We performed genotyping analyses for three single nucleotide
      polymorphisms (SNP) in the fibrinogen gene in a case-controlled study involving
      195 patients with CH and 116 control participants; both groups were of southern
      Han-Chinese origin. Logistic regression analysis indicated that haplotypes ATA
      (rs1800790+rs1800787+rs6050), AA (rs1800790+rs6050) and TA (rs1800787+rs6050)
      could nearly double the risk of sporadic CH (odds ratio [OR]=1.738, 95%
      confidence interval [CI]: 1.103-2.740, p=0.017; adjusted OR=1.762, 95% CI: 1.042
      2.982, p=0.035), although the three SNP were not associated with sporadic CH when
      analyzed separately. These findings indicate that rs1800790, rs1800787 and rs6050
      polymorphisms may contribute to the etiology of sporadic CH in the Chinese
      population.

PMID- 22386479
TI  - Minimally invasive transforaminal lumbar interbody fusion and spondylolisthesis.
AB  - The purpose of this study was to assess the clinical and radiological outcomes of
      minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) surgery for
      lumbar spondylolisthesis. A prospective analysis was conducted of 23 consecutive
      patients with grade I or grade II lumbar spondylolisthesis who underwent a MI
      TLIF using image guidance between August 2008 and September 2010. The patient
      group comprised 13 males and 10 females (mean age 57 years), 22 of whom underwent
      single level fusion and one patient with a two level fusion. All patients
      underwent postoperative CT scans to assess pedicle screw and cage placement and
      fusion at six months. The Oswestry Disability Index (ODI) scores were recorded
      preoperatively and at the six-month follow-up. We found that 22 of 23 (95.7%)
      patients showed evidence of fusion at six months with a mean improvement of 26.7
      on ODI scores. The mean length of hospital stay was four days. The mean operative
      time was 172 minutes. Anatomical reduction of the spondylolisthesis was complete
      in 16 patients and incomplete in seven. Regarding complications, we observed: one
      of 94 (1.1%) pedicle screws misplaced, which did not require revision
      postoperatively; one of 23 patients (4.3%) with a pulmonary embolism and one of
      23 (4.3%) patients with transient nerve root pain. There were no occurrences of
      infection and no postoperative cerebrospinal fluid leaks. We conclude that MI
      TLIF offers patients a safe and effective surgical option for lumbar
      spondylolisthesis treatment. Furthermore, it may offer patients additional
      advantages in terms of postoperative pain and recovery.

PMID- 22386480
TI  - Endoscopic endonasal management of trigeminal schwannomas extending into the
      infratemporal fossa.
AB  - Extracranial trigeminal schwannomas extending into the infratemporal fossa are
      rare. The traditional surgical approaches to the infratemporal fossa are
      associated with complications, such as facial nerve dysfunction, hearing loss,
      dental malocclusion and cosmetic problems. We report eight patients (four males,
      four females, age range=31-62 years) who were treated between 2004 and 2009 for
      extracranial trigeminal schwannomas extending into the infratemporal fossa.
      Schwannomas were surgically removed using a purely endoscopic endonasal approach.
      The maximum diameters of the tumours ranged from 30 mm to 70 mm and all tumours
      were completely removed. There were no intraoperative or postoperative
      complications in this series. There were no recurrences during the follow-up
      period which ranged from 10 to 74 months (mean=30 months). The purely endoscopic
      endonasal approach may provide a minimally invasive and safe approach to remove
      extracranial trigeminal schwannomas extending into the infratemporal fossa.
      Radical resection was associated with an excellent long-term outcome in this
      series.

PMID- 22386481
TI  - Moving molecular targeted drug therapy towards personalized medicine: issues
      related to clinical trial design.
AB  - With the event of new Molecular targets, clinical trial design requirements to
      perform these trials are changing. This paper discusses some of the
      considerations that need to be taken into account when designing a trial,
      including those trials that assess combinations of targets.

PMID- 22386482
TI  - [A sus-clavicular adenopathy in patient with PIP breast implants].

PMID- 22386483
TI  - Gold nanoparticles/horseradish peroxidase encapsulated polyelectrolyte
      nanocapsule for signal amplification in Listeria monocytogenes detection.
AB  - Bioconjugate nanocapsules were fabricated by using polystyrene sulfonate (PSS) to
      encapsulate gold nanoparticles (AuNPs) bearing adsorbed horseradish peroxidase
      (HRP). The average size of nanocapsule was in a range 150-400 nm. The efficiency
      of the capsules to enhance signals in an immunoassay was demonstrated by using an
      enzyme linked immunosorbent assay (ELISA) to detect the food-borne pathogen 
      Listeria monocytogenes. The antibody adsorbed onto the PSS shell of the
      nanocapsules provided the recognition molecule. For a given quantity of antibody,
      the bioconjugate nanocapsules showed 30 times greater sensitivity and a shorter
      assay time (5 min) when compared to conventional ELISA using an HRP labelled
      antibody. This proof-of-concept encapsulation of HRP through PSS nanocapsules may
      pave the way for alternative signal enhancement strategies where sensitivity is a
      priority.

PMID- 22386484
TI  - Rapid duplex immunoassay for wound biomarkers at the point-of-care.
AB  - In this study we describe a novel method of sampling and quantifying wound
      biomarkers for clinical settings. We believe the chosen format will allow rapid
      assessments of wound healing and provide biomarker evidence-based decision points
      for treatment of the wound at the time of presentation. The wound monitoring
      principle uses a proprietary sample collection tool (a thermally reversible
      hydrogel) to sample and isolate biomarkers within a wound environment without
      further sample extraction/preparation steps. We show how gel samples can be
      analysed in a lateral flow assay format utilising fluorescent microspheres with
      optically discrete emission characteristics and demonstrate quantitative
      detection of two analytes (duplexing) achieved in a single test line. As a model
      assay, the chronic wound biomarkers interleukin 6 (IL6) and tumour necrosis
      factor alpha (TNFalpha) are used. Limits of detection of 48.5 pg/mL and 55.5
      pg/mL respectively in hydrogel samples and 7.15 pg/mL and 10.7 pg/mL respectively
      in plasma are reported. We believe this is the first literature example of
      quantitative detection of multiple analytes within a single test line using
      spectral separation to distinguish the analytes.

PMID- 22386485
TI  - Optical immunosensor using carbon nanotubes coated with a photovoltaic polymer.
AB  - In this work, an on-chip optical immunosensor using an individually assembled
      carbon nanotube (CNT) coated with a photovoltaic polymer has been proposed,
      developed, characterized, and applied for the detection of cardiac biomarkers. An
      individual CNT was self-assembled on a nickel (Ni)-patterned electrode by
      magnetically attracting the residual iron catalyst at one end of the CNT. After
      the CNT self-assembled electrode was prepared, it was coated with a photovoltaic
      polymer to implement a CNT photodetector. Under an incident light, the
      photovoltaic polymer generated electrons that changed the conductivity of the
      CNT. The CNT photodetector was finally insulated with parylene to prevent
      interruptions of charged molecules in a sample solution, such as non-specifically
      bound proteins and various ions. Chemiluminescent immunoassay was directly
      performed on the CNT photodetector for an on-chip detection of cardiac troponin T
      (cTnT) with a detection limit of 12 pg/mL. High sensitivity and reliable
      selectivity have been achieved through the use of on-chip measurement of
      chemiluminescent light by the CNT photodetector. As a result, the developed
      device is envisaged as a new platform for optical immunosensing using the
      individually self-assembled CNT for point-of-care (POC) clinical diagnostics.

PMID- 22386486
TI  - Nanogold probe enhanced Surface Plasmon Resonance immunosensor for improved
      detection of antibiotic residues.
AB  - An exhaustive study is reported on the effect that antibody nanogold probes
      produce on the performance of a Surface Plasmon Resonance (SPR) immunosensor. The
      paper studies the improvement that different nanogold probes prepared at
      different antibody:gold nanoparticle (IgG:AuNP) ratios and AuNP sizes produce on
      the maximum signal and detectability of a simple SPR immunosensor developed to
      analyze fluoroquinolone (FQ) antibiotic residues (SPReeta system). The
      investigation compares the features of sensor enhanced formats using both,
      secondary and primary nanogold probes (anti-IgG and IgG coupled to AuNP, on
      double and single-antibody immunochemical assay steps, respectively), in respect
      to the unenhanced format. For this purpose, a reproducible bioconjugation
      procedure for preparing gold biohybrid nanoparticles has been established,
      involving the formation of a mixed self-assembled monolayer (m-SAM) with
      PEGylated cross-linkers around the AuNP followed by the covalent attachment of
      the antibodies. The procedure allows controlling the IgG:AuNP ratio of the
      nanogold probes on a reproducible manner and the functionalized NPs have been
      found to be stable during assay and storage. Both formats, using secondary and
      primary nanogold probes, are excellent strategies to improve immunosensor
      detectability. Thus, using anti-IgG-AuNP, the detectability could be improved by
      a factor of 14 (LOD 0.07+/-0.01 MUg L(-1) vs. 0.98+/-0.38 MUg L(-1)) reducing at
      the same time the amount of primary antibody used (30,000 vs. 1000 dilution
      factor). Likewise, the format using IgG-AuNP also allows improving detectability
      (LOD 0.11+/-0.01 MUg L(-1)), but reducing the number of needed steps.

PMID- 22386487
TI  - Preparation and application of novel nanocomposites of magnetic-Au nanorod in SPR
      biosensor.
AB  - A novel nanocomposite Fe(3)O(4)-Au nanorod (AuNR) was prepared and used as the
      substrate in the surface plasmon resonance (SPR) biosensor to detect goat IgM.
      Fe(3)O(4)-AuNR nanocomposites were synthesized by a method of seed-mediated
      growth, and further characterized by molecular absorption spectroscopy,
      transmission electronic microscopy (TEM), energy-dispersive spectroscopy (EDS)
      and X-ray photoelectron spectroscopy (XPS). The nanocomposites exhibit both
      magnetic property and exceptional optical property, which are beneficial to the
      antibody immobilization and the sensitivity of detection. The sensing membrane
      can be regenerated easily and the experimental procedure is simplified. Moreover,
      the Au nanorods show two plasmon resonance wavelengths defined as transverse mode
      and longitudinal mode, and the longitudinal plasmon wavelengths are more
      sensitive to the changes in the dielectric properties of the surroundings.
      Fe(3)O(4)-AuNR nanocomposites got a high sensitivity in detection of antibody
      antigen immunoassay. In the optimal conditions, the biosensor based on Fe(3)O(4)
      AuNR nanocomposites exhibits a satisfactory response to goat IgM in the
      concentration range of 0.15-40.00 MUg mL(-1). However, the biosensor without
      Fe(3)O(4)-AuNR nanocomposites shows a response to goat IgM in the concentration
      range of 1.25-40.00 MUg mL(-1). As a result, the sensitivity of the biosensor
      based on Fe(3)O(4)-AuNR nanocomposites is enhanced significantly.

PMID- 22386488
TI  - A "signal-on" electrochemical aptasensor for simultaneous detection of two tumor
      markers.
AB  - In this paper, we report a "signal-on" electrochemical aptasensor for
      simultaneous determination of two tumor markers MUC1 and VEGF(165), by using a
      ferrocene-labeled aptamer-complementary DNA (cDNA) as probe. Since the cDNA
      immobilized on an electrode surface can hybridize with both MUC1 aptamer and
      VEGF(165) aptamer to form a long double strand with ferrocene far away from the
      electrode surface, the probe cannot give electrochemical signal. Nevertheless,
      the presence of the two tumor markers will inhibit the hybridization of cDNA with
      the aptamers, thus the distance between ferrocene and the electrode is changed,
      and a "signal-on" electrochemical method to detect two tumor markers is
      developed. Experimental results show that the electrochemical signal increases
      with the addition of either tumor markers, but the biggest electrochemical signal
      can only be obtained when both tumor markers are present. Therefore, the proposed
      electrochemical aptasensor can not only detect the two markers but also
      distinguish their co-existence. It may also display high selectivity and
      sensitivity towards the detection of the tumor markers, so it might have
      potential clinical application in the future.

PMID- 22386489
TI  - Creating highly dense and uniform protein and DNA microarrays through
      photolithography and plasma modification of glass substrates.
AB  - We demonstrate a method to create high density protein microarrays with excellent
      spot uniformity using photolithography and plasma processing on low cost
      commercially available microscope glass slides. Protein deposition and
      fluorescence signal evaluation on these substrates are performed by standard
      arrayers and scanners. To this end, spots of commercial photoresists (AZ5214, SU8
      and Ormocomp((r))) were defined through lithography on glass substrates followed
      by short SF(6) plasma treatment and selective protein adsorption on these spots
      with respect to glass (spot to background fluorescence signal ratios 30:1 to
      40:1) was demonstrated using model protein binding assays. Among the photoresists
      tested, Ormocomp was selected since it provided the highest protein binding
      capacity. No ageing of Ormocomp/glass substrates in terms of protein binding
      capacity was observed for at least two months. Besides to protein microarrays,
      DNA microarrays were also developed by spotting streptavidin-biotinylated
      oligonucleotide conjugates corresponding to wild- and mutant-type sequences of
      four deleterious BRCA1 gene mutations. For all of the examined mutations, higher
      specific hybridization signals (1.5-4 times) and improved discrimination ratios
      between wild- and mutant-type sequences as well as higher spot uniformity and
      repeatability were demonstrated on Ormocomp/glass substrates with intra- and
      inter-spot CVs of 8.0% and 4.5%, respectively, compared to commercial polystyrene
      (intra- and inter-spot CVs 36% and 18%) and epoxy-coated glass (intra- and inter
      spot CVs 26% and 20%) slides. Thus, the proposed substrates can be readily
      applied to protein and DNA microarrays fabrication and, moreover, the described
      method for selective protein adsorption can be advantageously implemented in
      various analytical microdevices for multi-analyte detection.

PMID- 22386490
TI  - CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac
      troponin I for acute myocardial infarction diagnosis.
AB  - A label-free biosensor for electrical detection of cardiac troponin I (cTnI), a
      highly sensitive and selective biomarker of acute myocardial infarction (AMI), is
      demonstrated using silicon nanowire (SiNW) based field-effect transistors (FETs).
      The FET devices were fabricated by a complementary metal oxide semiconductor
      (CMOS) compatible top-down approach to define the SiNW followed by
      tetramethylammonium hydroxide (TMAH) wet etching. Electrical characterizations of
      the SiNW FET revealed an ambipolar conduction characteristic with an on/off ratio
      of 10(5)-10(6). CTnI monoclonal antibodies were then covalently immobilized on
      the SiNW surfaces. By integrating with a homemade biosensor measurement system,
      the biosensor exhibited rapid and sensitive response to cTnI proteins. The
      current response showed a nature of logarithm relationship against the cTnI
      concentration from 46 ng/mL down to 0.092 ng/mL. Moreover, an anti-interference
      capability of the fabricated biosensor was also assessed. By utilizing the top
      down fabrication method, this work provides an efficient way for the cTnI
      proteins detection with an enormous potential of mass-production, which
      definitely facilitate the practical applications.

PMID- 22386491
TI  - Visual detection of single-base mismatches in DNA using hairpin oligonucleotide
      with double-target DNA binding sequences and gold nanoparticles.
AB  - We describe a hairpin oligonucleotide (HO) with double-target DNA binding
      sequences in the loop and 11-base in the stem for visual detection of single-base
      mismatches (SBM) in DNA with highly specificity. The thiol-modified HO was
      immobilized on gold nanoparticle (Au-NP) surface through a self-assembling
      process. The strategy of detecting SBM depends on the unique molecular
      recognition properties of HO to the perfect-matched DNA and SBM to generate
      different quantities of duplex DNA on the Au-NP surface, which are captured on
      the test zone of lateral flow test strip via the DNA hybridization reaction
      between the duplex DNA and preimmobilized DNA probe. Accumulation of Au-NPs
      produces the characteristic red bands, enabling visual detection of SBM. It was
      found that the ability of HO to differentiate perfect-matched DNA and SBM was
      increased dramatically by incorporating double-target DNA binding sequences in
      the loop of HO. The signal ratio between perfect-matched DNA and SBM was up to
      28, which is much higher than that of conventional HO or molecular beacon. The
      approach was applied to detect the mutation sites, Arg142Cys and Gly529Ile, of
      transglutaminase 1 gene in autosomal recessive congenital ichthyosis. The results
      presented here show that the new HO is a potential molecular recognition probe
      for the future development of nucleic acid-based biosensors and bioassays. The
      approach can be used for point-of-care diagnosis of genetic diseases and
      detecting infectious agents or warning against bio-warfare agents.

PMID- 22386492
TI  - Decreased interferon-alpha production in response to CpG DNA dysregulates
      cytokine responses in patients with multiple sclerosis.
AB  - Type I interferons (IFNs), represented by IFN-alpha and beta, activate immune
      effector cells belonging to the innate and adaptive immune systems. Plasmacytoid
      dendritic cells (pDCs) produce IFN-alpha in response to CpG DNA. We aimed to
      examine the impact of pDC-produced IFN-alpha on the adaptive immune system in
      Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-alpha
      production was significantly decreased in PBMCs from MS patients. Decreased
      levels of IL-12 p70, IFN-gamma, and IL-17 and increased level of IL-10 were found
      in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In
      samples pre-treated with IFN-alpha and IFN-beta, decreased levels of IL-12 p70,
      IFN-gamma, and IL-17 and increased level of IL-10 were detected in PBMCs from MS
      patients. These results suggest that CpG DNA-induced decreased IFN-alpha
      production causes pro-inflammatory cytokine secretion, and either IFN-alpha or
      IFN-beta induces anti-inflammatory cytokine secretion in the adaptive immune
      system in MS.

PMID- 22386493
TI  - Interactions among flavonoids of propolis affect antibacterial activity against
      the honeybee pathogen Paenibacillus larvae.
AB  - Propolis is derived from plant resins, collected by honeybees (Apis mellifera)
      and renown for its antibacterial properties. Here we test the antibacterial
      effects of ethanolic extracts of propolis from different origins on Paenibacillus
      larvae, the bacterial pathogen that causes American Foulbrood, a larval disease
      that can kill the honeybee colony. All tested propolis samples inhibited
      significantly the growth of P. larvae tested in vitro. The extracts showed major
      differences in the content of total flavonoids (ranging from 2.4% to 16.4%) and
      the total polyphenols (ranging between 23.3% and 63.2%). We found that it is not
      only the content of compounds in propolis, which influences the strength of
      antimicrobial effects but there is also a significant interaction effect among
      flavonoids of the propolis extracts. We propose that interaction effects among
      the various chemical compounds in propolis should be taken into account when
      considering the antibacterial effects against honeybee pathogens.

PMID- 22386495
TI  - Distinct models of induced hyperactivity in zebrafish larvae.
AB  - The analysis of behavioural hyperactivity can provide insights into how
      perturbations in normal activity may be linked to the altered function of the
      nervous system and possibly the symptoms of disease. As a small vertebrate
      zebrafish have numerous experimental advantages that are making them a powerful
      model for these types of studies. While the majority of behavioural studies have
      focused on adult zebrafish, it has become apparent that larvae can also display
      complex stereotypical patterns of behaviour. Here we have used three compounds
      (pentylenetetrazole (PTZ), aconitine and 4-aminopyridine) that have different
      neuronal targets (GABA, sodium and potassium channels), to induce distinct
      patterns of hyperactivity in larvae. Our studies have revealed that each compound
      produces a number of distinct concentration-dependent activity patterns. This
      work has shown for the first time that at sub-convulsive concentrations, PTZ can
      reverse the normal behavioural response to alternating periods of light and dark
      in zebrafish larvae. It also appears that both PTZ and 4-aminopyridine produce
      distinct changes in the normal startle response patterns immediately following
      light/dark transitions that may be the result of an elevation in stress/anxiety.
      Aconitine produces a general elevation in activity that eliminates the normal
      response to light and dark. In addition to differences in the patterns of
      behaviour each compound also produces a unique pattern of c-fos (an immediate
      early gene) expression in the brain. While more work is required to make direct
      links between region specific neuronal activity and individual behaviours, these
      models provide a framework with which to study and compare mechanistically
      different types of inducible behaviours.

PMID- 22386494
TI  - Nerve growth factor and brain-derived neurotrophic factor but not granulocyte
      colony-stimulating factor, nimodipine and dizocilpine, require ATP for
      neuroprotective activity after oxygen-glucose deprivation of primary neurons.
AB  - In previous work, we have demonstrated by radiolabeling, mass spectrometry and
      site-directed mutagenesis that nerve growth factor (NGF) as well as brain-derived
      neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are capable of
      ATP-binding and that this binding appears to be essential for their
      neuroprotective activity. In this study, we attempted to shed some light on the
      question whether ATP is a general prerequisite for neuroprotection. Therefore, we
      used the non-ATP-binding granulocyte colony-stimulating factor (GCSF), the
      calcium antagonist nimodipine and the NMDA antagonist dizocilpine to find out
      whether they need ATP for neuroprotection comparable to NGF and BDNF. However,
      ATP was not necessary for the neuroprotective effects of GCSF, nimodipine and
      dizocilpine on primary cultures of rat cortical neurons damaged by oxygen-glucose
      deprivation whereas neuroprotection was demonstrable for NGF and BDNF only when
      ATP was present in the culture medium at a concentration higher than ca.
      0.4nmol/l. In circular dichroism studies ATP caused changes of the secondary
      structure of NGF but not of GCSF. Taken together, we suggest that ATP is not a
      general prerequisite for neuroprotectivity but some growth factors like NGF and
      BDNF can stimulate their receptors only if they have bound ATP.

PMID- 22386496
TI  - Generation and characterization of hD5 and C-terminal Mutant hD(5m) transgenic
      rats.
AB  - Dopamine D1-like receptors play important roles in many brain activities such as
      cognition and emotion. We have generated human hD5 and mutant human hD5 (hD(5m))
      transgenic rats. The C-terminal juxtamembrane domain of mutant hD5 was identical
      to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter
      that led the expression mainly in the cerebral cortex and hippocampus. We have
      used different dopamine receptor agonists to compare the pharmacological profiles
      of the human hD5 and hD(5m) receptors. The results showed that they exhibited
      distinct pharmacological properties. Our results of pharmacological studies
      indicated that the C-terminal of D5 receptor could play important roles in
      agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by
      tetanic stimulation was significantly reduced in both transgenic rats. In
      addition, we found that the overexpression of dopamine hD5 and hD(5m) receptors
      in the rat brain resulted in memory impairments. Interestingly, an atypical D1
      like receptor agonist, SKF83959, could induce anxiety in hD(5m) receptor
      transgenic rats but had no effect on the anxiety-like behavior in D5 receptor
      transgenic and wild-type rats.

PMID- 22386497
TI  - Palliative surgery for skeletal metastases from melanoma in the scaphoid--a
      critical case report appraisal.
AB  - A 46-year-old woman with a history of metastatic malignant melanoma presented
      with what appeared to be a scaphoid nonunion. Biopsy and subsequent scaphoid
      excision confirmed the diagnosis of metastatic melanoma. Her quality of life was
      improved for her remaining 13 months by scaphoid excision. We assessed our
      results in relation to the literature.

PMID- 22386498
TI  - Evaluating keloid recurrence after surgical excision with prospective
      longitudinal scar assessment scales.
AB  - INTRODUCTION: Evaluation tools are used to quantify scar evolution and determine
      treatment effectiveness. In clinical practice, scar assessment scales are less
      costly, tend to cover a greater number of aspects related to scar characteristics
      and can incorporate a patient's opinion in the assessment. However, the scales
      have not yet been used as an evaluation method for the postoperative recurrence
      of keloids. OBJECTIVE: The study aims to evaluate the effectiveness of scar
      rating scales for keloid recurrence after surgical excision. METHODS: Patients (n
      = 25) with keloids on the trunk were treated by surgical resection and
      postoperative beta radiation therapy. On the 3rd, 6th, 9th and 12th postoperative
      months, two specialists classified the lesions qualitatively in recurrent and non
      recurrent cases. Furthermore, in the objective evaluation, the items on the
      Seattle Scar Scale (SSS) and the Stony Brook Scar Evaluation Scale (SBSES) were
      assessed by specialists, and the patients assessed items on the Patient Scar
      Assessment Scale (PSAS) for the pre- and postoperative periods. The scars were
      classified qualitatively as "good" or "poor." RESULTS: Recurrence was observed in
      18 patients (72%), according to the specialists' qualitative assessments. The
      best scores on the SSS and SBSES were given to the non-recurrent (p < 0.001)
      scars. The highest PSAS values were for the scars classified as "poor" (p <
      0.001). There were no differences in the PSAS values for the preoperative period
      and outcomes for the recurrent scars (p = 0.519). The outcomes showed that the
      non-recurrent scars had lower values on the PSAS compared to the recurrent scars
      (p = 0.001) and compared to the preoperative period (p = 0.004). CONCLUSIONS: The
      PSAS, SSS and SBSES scales were effective methods in distinguishing keloid
      postoperative recurrence. It is necessary to establish the recurrence cut-off
      scores for each of the scales according to the treatment used.

PMID- 22386499
TI  - Can we teach moderate intensity activity? Adult perception of moderate intensity
      walking.
AB  - OBJECTIVES: To investigate how people determine the intensity of their physical
      activity, respond to instruction, and their understanding of moderate intensity
      walking. DESIGN: Experimental. METHODS: Forty nine regular walkers had their
      walking speed, heart rate and rate of perceived exertion measured during their
      normal walking behaviour, when instructed to walk at a moderate intensity, and
      after provision of feedback on how to meet moderate intensity walking. RESULTS:
      Although moderate intensity walking was generally perceived as too low to be
      beneficial, walking speed was the best variable matched across all experiments
      for moderate intensity (83.7%, 67.3% and 93.9%), followed by heart rate, with a
      large proportion of participants responding favourably to instruction relating to
      heart rate and speed to meet moderate intensity walking. Rate of perceived
      exertion was a poor reflector of walking intensity. CONCLUSION: Most participants
      naturally selected a walking intensity that elicits moderate intensity and when
      instructed to walk at moderate intensity, the intensity is more vigorous.
      Attempting to match speed and heart rate limits for moderate intensity reduced
      the intensity perceived by participants.

PMID- 22386500
TI  - A forecast-based STDP rule suitable for neuromorphic implementation.
AB  - Artificial neural networks increasingly involve spiking dynamics to permit
      greater computational efficiency. This becomes especially attractive for on-chip
      implementation using dedicated neuromorphic hardware. However, both spiking
      neural networks and neuromorphic hardware have historically found difficulties in
      implementing efficient, effective learning rules. The best-known spiking neural
      network learning paradigm is Spike Timing Dependent Plasticity (STDP) which
      adjusts the strength of a connection in response to the time difference between
      the pre- and post-synaptic spikes. Approaches that relate learning features to
      the membrane potential of the post-synaptic neuron have emerged as possible
      alternatives to the more common STDP rule, with various implementations and
      approximations. Here we use a new type of neuromorphic hardware, SpiNNaker, which
      represents the flexible "neuromimetic" architecture, to demonstrate a new
      approach to this problem. Based on the standard STDP algorithm with modifications
      and approximations, a new rule, called STDP TTS (Time-To-Spike) relates the
      membrane potential with the Long Term Potentiation (LTP) part of the basic STDP
      rule. Meanwhile, we use the standard STDP rule for the Long Term Depression (LTD)
      part of the algorithm. We show that on the basis of the membrane potential it is
      possible to make a statistical prediction of the time needed by the neuron to
      reach the threshold, and therefore the LTP part of the STDP algorithm can be
      triggered when the neuron receives a spike. In our system these approximations
      allow efficient memory access, reducing the overall computational time and the
      memory bandwidth required. The improvements here presented are significant for
      real-time applications such as the ones for which the SpiNNaker system has been
      designed. We present simulation results that show the efficacy of this algorithm
      using one or more input patterns repeated over the whole time of the simulation.
      On-chip results show that the STDP TTS algorithm allows the neural network to
      adapt and detect the incoming pattern with improvements both in the reliability
      of, and the time required for, consistent output. Through the approximations we
      suggest in this paper, we introduce a learning rule that is easy to implement
      both in event-driven simulators and in dedicated hardware, reducing computational
      complexity relative to the standard STDP rule. Such a rule offers a promising
      solution, complementary to standard STDP evaluation algorithms, for real-time
      learning using spiking neural networks in time-critical applications.

PMID- 22386501
TI  - Extraction of temporally correlated features from dynamic vision sensors with
      spike-timing-dependent plasticity.
AB  - A biologically inspired approach to learning temporally correlated patterns from
      a spiking silicon retina is presented. Spikes are generated from the retina in
      response to relative changes in illumination at the pixel level and transmitted
      to a feed-forward spiking neural network. Neurons become sensitive to patterns of
      pixels with correlated activation times, in a fully unsupervised scheme. This is
      achieved using a special form of Spike-Timing-Dependent Plasticity which
      depresses synapses that did not recently contribute to the post-synaptic spike
      activation, regardless of their activation time. Competitive learning is
      implemented with lateral inhibition. When tested with real-life data, the system
      is able to extract complex and overlapping temporally correlated features such as
      car trajectories on a freeway, after only 10 min of traffic learning. Complete
      trajectories can be learned with a 98% detection rate using a second layer, still
      with unsupervised learning, and the system may be used as a car counter. The
      proposed neural network is extremely robust to noise and it can tolerate a high
      degree of synaptic and neuronal variability with little impact on performance.
      Such results show that a simple biologically inspired unsupervised learning
      scheme is capable of generating selectivity to complex meaningful events on the
      basis of relatively little sensory experience.

PMID- 22386502
TI  - The grounding of higher order concepts in action and language: a cognitive
      robotics model.
AB  - In this paper we present a neuro-robotic model that uses artificial neural
      networks for investigating the relations between the development of symbol
      manipulation capabilities and of sensorimotor knowledge in the humanoid robot
      iCub. We describe a cognitive robotics model in which the linguistic input
      provided by the experimenter guides the autonomous organization of the robot's
      knowledge. In this model, sequences of linguistic inputs lead to the development
      of higher-order concepts grounded on basic concepts and actions. In particular,
      we show that higher-order symbolic representations can be indirectly grounded in
      action primitives directly grounded in sensorimotor experiences. The use of
      recurrent neural network also permits the learning of higher-order concepts based
      on temporal sequences of action primitives. Hence, the meaning of a higher-order
      concept is obtained through the combination of basic sensorimotor knowledge. We
      argue that such a hierarchical organization of concepts can be a possible account
      for the acquisition of abstract words in cognitive robots.

PMID- 22386503
TI  - Learning expectation in insects: a recurrent spiking neural model for spatio
      temporal representation.
AB  - Insects are becoming a reference point in Neuroscience for the study of
      biological aspects at the basis of cognitive processes. These animals have much
      simpler brains with respect to higher animals, showing, at the same time,
      impressive capability to adaptively react and take decisions in front of complex
      environmental situations. In this paper we propose a neural model inspired by the
      insect olfactory system, with particular attention to the fruit fly Drosophila
      melanogaster. This architecture is a multilayer spiking network, where each layer
      is inspired by the structures of the insect brain mainly involved in olfactory
      information processing, namely the Mushroom Bodies, the Lateral Horns and the
      Antennal Lobes. In the Antennal Lobes layer olfactory signals lead to a
      competition among sets of neurons, resulting in a pattern which is projected to
      the Mushroom Bodies layer. Here a competitive reaction-diffusion process leads to
      a spontaneous emerging of clusters. The Lateral Horns have been modeled as a
      delayed input-triggered resetting system. Using plastic recurrent connections,
      with the addition of simple learning mechanisms, the structure is able to realize
      a top-down modulation at the input level. This leads to the emergence of an
      attentional loop as well as to the arousal of basic expectation behaviors in case
      of subsequently presented stimuli. Simulation results and analysis on the
      biological plausibility of the architecture are provided and the role of noise in
      the network is reported.

PMID- 22386504
TI  - Asthma outcomes workshop: overview.
AB  - BACKGROUND: Asthma clinical research will highly benefit from standardization of
      major outcomes in terms of definition and assessment methodology. This will
      permit useful comparisons across interventional or observational studies and will
      allow more effective data sharing. OBJECTIVE: National Institutes of Health (NIH)
      institutes and the Agency for Healthcare Research and Quality convened a workshop
      involving 7 expert subcommittees to propose which asthma outcomes should be
      assessed with standardized methodology in future asthma clinical research
      studies. METHODS: Each subcommittee utilized comprehensive literature reviews and
      expert opinion to compile a list of asthma outcomes and classified them as either
      core (required in future studies), supplemental (to be used according to study
      aims and standardized), or emerging (requiring validation and standardization).
      This work was discussed at an NIH-organized workshop in March 2010 and finalized
      in September 2011. RESULTS: Outcomes for study participant characterization, as
      well as for prospective clinical trial intervention and observational studies,
      were proposed for adults and children, and methodologies for outcome collection
      and reporting were determined. Furthermore, the workshop identified areas in
      which new outcomes or instruments for their measurement need to be developed and
      validated. CONCLUSIONS: Standardized outcomes for clinical research in asthma
      have been proposed. Participating NIH institutes and other federal agencies will
      consider these recommendations in future clinical research initiatives in asthma.

PMID- 22386505
TI  - Asthma outcomes: symptoms.
AB  - BACKGROUND: Respiratory symptoms are commonly used to assess the impact of
      patient-centered interventions. OBJECTIVE: At the request of National Institutes
      of Health (NIH) institutes and other federal agencies, an expert group was
      convened to propose which measurements of asthma symptoms should be used as a
      standardized measure in future clinical research studies. METHODS: Asthma symptom
      instruments were classified as daily diaries (prospectively recording symptoms
      between research visits) or retrospective questionnaires (completed at research
      visits). We conducted a systematic search in PubMed and a search for articles
      that cited key studies describing development of instruments. We classified
      outcome instruments as either core (required in future studies), supplemental
      (used according to study aims and standardized), or emerging (requiring
      validation and standardization). This work was discussed at an NIH-organized
      workshop in March 2010 and finalized in September 2011. RESULTS: Four instruments
      (3 daily diaries, 1 for adults and 2 for children; and 1 retrospective
      questionnaire for adults) were identified. Minimal clinically important
      differences have not been established for these instruments, and validation
      studies were only conducted in a limited number of patient populations. Validity
      of existing instruments may not be generalizable across racial-ethnic or other
      subgroups. CONCLUSIONS: An evaluation of symptoms should be a core asthma outcome
      measure in clinical research. However, available instruments have limitations
      that preclude selection of a core instrument. The working group participants
      propose validation studies in diverse populations, comparisons of diaries versus
      retrospective questionnaires, and evaluations of symptom assessment alone versus
      composite scores of asthma control.

PMID- 22386506
TI  - Mediators of asthma outcomes.
AB  - BACKGROUND: Patient adherence, the level of asthma self-management skills,
      exposure to stress, and depression can have considerable influence on a wide
      range of asthma outcomes and thus are considered asthma outcome mediators.
      OBJECTIVE: National Institutes of Health institutes and other federal agencies
      convened an expert group to recommend standardized measures for 7 domains of
      asthma clinical research outcomes measures. Although the review of mediators of
      these outcomes was not within the scope of any specific outcome topic, a brief
      summary is presented so that researchers might consider potential mediators.
      METHODS: We prepared a summary of key mediators of asthma outcomes based on
      expertise and knowledge of the literature. RESULTS: The rationale for including
      measures of adherence, self-management skills, and exposures to stress in asthma
      clinical research is presented, along with a brief review of instruments for
      collecting this information from clinical research participants. CONCLUSIONS:
      Appropriate measurement of adherence, self-management skills, and exposures to
      stress will enhance characterization of study participants and provide
      information about the potential impact these factors can have on mediating the
      effects of treatment interventions.

PMID- 22386507
TI  - Asthma outcomes: composite scores of asthma control.
AB  - BACKGROUND: Current asthma guidelines recommend assessing the level of a
      patient's asthma control. Consequently, there is increasing use of asthma control
      as an outcome measure in clinical research studies. Several composite assessment
      instruments have been developed to measure asthma control. OBJECTIVE: National
      Institutes of Health institutes and federal agencies convened an expert group to
      propose the most appropriate standardized composite score of asthma control
      instruments to be used in future asthma studies. METHODS: We conducted a
      comprehensive search of PubMed using both the National Library of Medicine's
      Medical Subject Headings and key terms to identify studies that attempted to
      develop and/or test composite score instruments for asthma control. We classified
      instruments as core (required in future studies), supplemental (used according to
      study aims and standardized), or emerging (requiring validation and
      standardization). This work was discussed at a National Institutes of Health
      organized workshop convened in March 2010 and finalized in September 2011.
      RESULTS: We identified 17 composite score instruments with published validation
      information; all had comparable content. Eight instruments demonstrated
      responsiveness over time; 3 demonstrated responsiveness to treatment. A minimal
      clinically important difference has been established for 3 instruments. The
      instruments have demographic limitations; some are proprietary, and their use
      could be limited by cost. CONCLUSION: Two asthma composite score instruments are
      sufficiently validated for use in adult populations, but additional research is
      necessary to validate their use in nonwhite populations. Gaps also exist in
      validating instruments for pediatric populations.

PMID- 22386508
TI  - Asthma outcomes: exacerbations.
AB  - BACKGROUND: The goals of asthma treatment include preventing recurrent
      exacerbations. Yet there is no consensus about the terminology for describing or
      defining "exacerbation" or about how to characterize an episode's severity.
      OBJECTIVE: National Institutes of Health institutes and other federal agencies
      convened an expert group to propose how asthma exacerbation should be assessed as
      a standardized asthma outcome in future asthma clinical research studies.
      METHODS: We used comprehensive literature reviews and expert opinion to compile a
      list of asthma exacerbation outcomes and classified them as either core (required
      in future studies), supplemental (used according to study aims and standardized),
      or emerging (requiring validation and standardization). This work was discussed
      at a National Institutes of Health-organized workshop in March 2010 and finalized
      in September 2011. RESULTS: No dominant definition of "exacerbation" was found.
      The most widely used definitions included 3 components, all related to treatment,
      rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific
      emergency department visits or hospitalizations, and (3) use of short-acting beta
      agonists as quick-relief (sometimes referred to as "rescue" or "reliever")
      medications. CONCLUSIONS: The working group participants propose that the
      definition of "asthma exacerbation" be "a worsening of asthma requiring the use
      of systemic corticosteroids to prevent a serious outcome." As core outcomes, they
      propose inclusion and separate reporting of several essential variables of an
      exacerbation. Furthermore, they propose the development of a standardized,
      component-based definition of "exacerbation" with clear thresholds of severity
      for each component.

PMID- 22386509
TI  - Asthma outcomes: healthcare utilization and costs.
AB  - BACKGROUND: Measures of healthcare utilization and indirect impact of asthma
      morbidity are used to assess clinical interventions and estimate cost. OBJECTIVE:
      National Institutes of Health institutes and other federal agencies convened an
      expert group to propose standardized measurement, collection, analysis, and
      reporting of healthcare utilization and cost outcomes in future asthma studies.
      METHODS: We used comprehensive literature reviews and expert opinion to compile a
      list of asthma healthcare utilization outcomes that we classified as core
      (required in future studies), supplemental (used according to study aims and
      standardized), and emerging (requiring validation and standardization). We also
      have identified methodology to assign cost to these outcomes. This work was
      discussed at an National Institutes of Health-organized workshop in March 2010
      and finalized in September 2011. RESULTS: We identified 3 ways to promote
      comparability across clinical trials for measures of healthcare utilization,
      resource use, and cost: (1) specify the study perspective (patient, clinician,
      payer, and society); (2) standardize the measurement period (ideally 12 months);
      and (3) use standard units to measure healthcare utilization and other asthma
      related events. CONCLUSIONS: Large clinical trials and observational studies
      should collect and report detailed information on healthcare utilization,
      intervention resources, and indirect impact of asthma, so that costs can be
      calculated and cost-effectiveness analyses can be conducted across several
      studies. Additional research is needed to develop standard, validated survey
      instruments for collection of provider-reported and participant-reported data
      regarding asthma-related health care.

PMID- 22386510
TI  - Asthma outcomes: pulmonary physiology.
AB  - BACKGROUND: Outcomes of pulmonary physiology have a central place in asthma
      clinical research. OBJECTIVE: At the request of National Institutes of Health
      (NIH) institutes and other federal agencies, an expert group was convened to
      provide recommendations on the use of pulmonary function measures as asthma
      outcomes that should be assessed in a standardized fashion in future asthma
      clinical trials and studies to allow for cross-study comparisons. METHODS: Our
      subcommittee conducted a comprehensive search of PubMed to identify studies that
      focused on the validation of various airway response tests used in asthma
      clinical research. The subcommittee classified the instruments as core (to be
      required in future studies), supplemental (to be used according to study aims and
      in a standardized fashion), or emerging (requiring validation and
      standardization). This work was discussed at an NIH-organized workshop in March
      2010 and finalized in September 2011. RESULTS: A list of pulmonary physiology
      outcomes that applies to both adults and children older than 6 years was created.
      These outcomes were then categorized into core, supplemental, and emerging.
      Spirometric outcomes (FEV(1), forced vital capacity, and FEV(1)/forced vital
      capacity ratio) are proposed as core outcomes for study population
      characterization, for observational studies, and for prospective clinical trials.
      Bronchodilator reversibility and prebronchodilator and postbronchodilator FEV(1)
      also are core outcomes for study population characterization and observational
      studies. CONCLUSIONS: The subcommittee considers pulmonary physiology outcomes of
      central importance in asthma and proposes spirometric outcomes as core outcomes
      for all future NIH-initiated asthma clinical research.

PMID- 22386511
TI  - Asthma outcomes: quality of life.
AB  - BACKGROUND: "Asthma-related quality of life" (QOL) refers to the perceived impact
      that asthma has on the patient's QOL. OBJECTIVE: National Institutes of Health
      institutes and other federal agencies convened an expert group to recommend
      standardized measures of the impact of asthma on QOL for use in future asthma
      clinical research. METHODS: We reviewed published documentation regarding the
      development and psychometric evaluation; clinical research use since 2000; and
      extent to which the content of each existing QOL instrument provides a unique,
      reliable, and valid assessment of the intended construct. We classified
      instruments as core (required in future studies), supplemental (used according to
      the study's aims and standardized), or emerging (requiring validation and
      standardization). This work was discussed at an National Institutes of Health
      organized workshop convened in March 2010 and finalized in September 2011.
      RESULTS: Eleven instruments for adults and 6 for children were identified for
      review. None qualified as core instruments because they predominantly measured
      indicators of asthma control (symptoms and/or functional status); failed to
      provide a distinct, reliable score measuring all key dimensions of the intended
      construct; and/or lacked adequate psychometric data. CONCLUSIONS: In the absence
      of existing instruments that meet the stated criteria, currently available
      instruments are classified as either supplemental or emerging. Research is
      strongly recommended to develop and evaluate instruments that provide a distinct,
      reliable measure of the patient's perception of the impact of asthma on all of
      the key dimensions of QOL, an important outcome that is not captured in other
      outcome measures.

PMID- 22386513
TI  - Organic matter content and particle size modifications in mangrove sediments as
      responses to sea level rise.
AB  - Mangroves sediments contain large reservoirs of organic material (OM) as mangrove
      ecosystems produce large quantities and rapidly burial OM. Sediment accumulation
      rates of approximately 2.0 mm year(-1), based on (210)Pb(ex) dating, were
      estimated at the margin of two well-developed mangrove forest in southern Brazil.
      Regional data point to a relative sea level (RSL) rise of up to ~4.0 mm year(-1).
      This RSL rise in turn, may directly influence the origin and quantity of organic
      matter (OM) deposited along mangrove sediments. Lithostratigraphic changes show
      that sand deposition is replacing the mud (<63 MUm) fraction and OM content is
      decreasing in successively younger sediments. Sediment accumulation in coastal
      areas that are not keeping pace with sea level rise is potentially conducive to
      the observed shifts in particle size and OM content.

PMID- 22386514
TI  - Can intensity-modulated radiotherapy preserve oral health-related quality of life
      of nasopharyngeal carcinoma patients?
AB  - PURPOSE: To investigate the changes in salivary function and oral health-related
      quality of life for patients with nasopharyngeal carcinoma treated by intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 57 patients with
      early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva
      flow was measured, and the Medical Outcomes Study 36-item short form, European
      Organization for Research and Treatment of Cancer Quality of Life questionnaire
      C30, European Organization for Research and Treatment of Cancer Quality of Life
      questionnaire 35-item head-and-neck module, and Oral Health Impact Profile
      questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after
      IMRT. RESULTS: Parotid saliva flow recovered fully after 1 year and maintained.
      Whole saliva flow recovered partially to 40% of baseline. A general trend of
      deterioration in most quality of life scales was observed after IMRT, followed by
      gradual recovery. Persistent oral-related symptoms were found 2 years after
      treatment. CONCLUSION: IMRT for early-stage nasopharyngeal carcinoma could only
      partially preserve the whole salivary function and oral health-related quality of
      life.

PMID- 22386512
TI  - Asthma outcomes: biomarkers.
AB  - BACKGROUND: Measurement of biomarkers has been incorporated within clinical
      research studies of asthma to characterize the population and associate the
      disease with environmental and therapeutic effects. OBJECTIVE: National
      Institutes of Health institutes and federal agencies convened an expert group to
      propose which biomarkers should be assessed as standardized asthma outcomes in
      future clinical research studies. METHODS: We conducted a comprehensive search of
      the literature to identify studies that developed and/or tested asthma
      biomarkers. We identified biomarkers relevant to the underlying disease process
      progression and response to treatment. We classified the biomarkers as either
      core (required in future studies), supplemental (used according to study aims and
      standardized), or emerging (requiring validation and standardization). This work
      was discussed at an National Institutes of Health-organized workshop convened in
      March 2010 and finalized in September 2011. RESULTS: Ten measures were
      identified; only 1, multiallergen screening to define atopy, is recommended as a
      core asthma outcome. Complete blood counts to measure total eosinophils,
      fractional exhaled nitric oxide (Feno), sputum eosinophils, urinary leukotrienes,
      and total and allergen-specific IgE are recommended as supplemental measures.
      Measurement of sputum polymorphonuclear leukocytes and other analytes, cortisol
      measures, airway imaging, breath markers, and system-wide studies (eg, genomics,
      proteomics) are considered as emerging outcome measures. CONCLUSION: The working
      group participants propose the use of multiallergen screening in all asthma
      clinical trials to characterize study populations with respect to atopic status.
      Blood, sputum, and urine specimens should be stored in biobanks, and standard
      procedures should be developed to harmonize sample collection for clinical trial
      biorepositories.

PMID- 22386515
TI  - Improvement of deficits by transplantation of lentiviral vector-modified human
      amniotic mesenchymal cells after cerebral ischemia in rats.
AB  - Amniotic membrane is known to have the ability to transdifferentiate into
      multiple organs and is expected to stimulate a reduced immunologic reaction.
      Human amniotic membrane-derived mesenchymal stem cells (hAMCs) do not express the
      major histocompatibility complex (MHC) class I molecule and may be expected to
      show immunologic tolerance. A good deal of research has explored the clinical
      therapeutic potential of hAMCs. In the present study, we isolated hAMCs and
      transfected them with the brain derived neurotrophic factor (BDNF) gene using
      lentiviral vectors. These cells were then transplanted into the brains of rats
      subjected to a transient middle cerebral artery occlusion (MCAO). The hAMCs
      survived for three weeks in the brains of the ischemic rats, and some of the
      transplanted hAMCs expressed the neuronal marker MAP2 and the neuronal progenitor
      marker Nestin. Furthermore, caspase-3 activity and iNOS expression were decreased
      in the vicinity of the graft and injection site. Importantly, intracerebral
      grafting of EGFP-modified hAMCs and BDNF-transduced hAMCs significantly
      ameliorated behavioral dysfunction in ischemic rats. BDNF-hAMCs ameliorated the
      behavioral dysfunction of rats more rapidly and effectively relative to EGFP-hAMC
      treated rats. Finally, the grafts also reduced the infarct volume. hAMCs survived
      in the brain tissue and improved functional recovery. Because of the lack of
      ethical concerns and the high supply of these cells, hAMCs represent a promising
      clinical treatment for gene delivery similar to stem cell strategies.

PMID- 22386516
TI  - Effects of lesions of the amygdala central nucleus on autoshaped lever pressing.
AB  - Neutral cues paired with rewards often appear to acquire motivational
      significance, as if the incentive motivational value of the reward is transferred
      to the cue. Such cues have been reported to modulate the performance of
      instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned
      reinforcers in the establishment of new learning, and be the targets of approach
      and other cue-directed behaviors. Here we examined the effects of lesions of the
      amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped
      lever-pressing. Insertion of one lever into the experimental chamber was
      reinforced by sucrose delivery, but insertion of another lever was not
      reinforced. Although sucrose delivery was not contingent on lever pressing, both
      CeA- and sham-lesioned rats rapidly came to press the reinforced but not the
      nonreinforced lever. Despite their showing little evidence of impairments in
      autoshaped lever pressing, these same CeA-lesioned rats showed significant
      deficits in the expression of PIT in a subsequent phase of the experiment. The
      lack of impaired autoshaping in CeA-lesioned rats contrasts with effects
      previously reported for conditioned orienting responses (ORs) and for other
      putative measures of incentive learning including PIT and conditioned approach to
      visual cues.

PMID- 22386518
TI  - Virus-like particles and alpha-galactosylceramide form a self-adjuvanting
      composite particle that elicits anti-tumor responses.
AB  - Virus-like particles (VLP) are effective vehicles for delivery of heterologous
      antigen to antigen-presenting cells. However VLP alone are insufficiently
      stimulatory to generate the signals required to facilitate effective priming of
      naive T cells. We show that the VLP derived from rabbit hemorrhagic disease virus
      can bind the galactose-containing adjuvant alpha-galactosylceramide to form a
      composite particle for co-delivery of antigen and adjuvant to the same antigen
      presenting cell. Vaccination with VLP and alpha-galactosylceramide activated
      splenic iNKT cells to produce IFN-gamma and IL-4, led to the generation of
      antigen-specific T cells that protected prophylactically against subcutaneous
      tumor challenge, and was more effective at generating anti-tumor immune responses
      than either component individually. These data demonstrate a novel method for
      immunopotentiating VLP to increase their efficacy in the generation of anti-tumor
      responses via the innate ligand recognition properties of calicivirus-derived
      nanoparticles.

PMID- 22386519
TI  - Structural organization of the nuclear pore permeability barrier.
AB  - The efficiency of gene therapy in non-dividing cells is particularly poor due to
      restricted nuclear delivery rates of exogenously applied macromolecules across
      the nuclear pore complexes (NPCs). Therefore, improved intranuclear delivery of
      transgenes requires an ability to modulate the barrier function of the NPC.
      Despite a large body of experimental evidence accumulated to date, the
      contribution of individual NPC proteins (nucleoporins) to the formation of the
      NPC permeability barrier as well as their structural organization within the NPC
      remains under debate. In the present study, we revisit the view on the spatial
      arrangement of the Phe-Gly rich domains (FG-domains) of a subset of nucleoporins
      known as FG-nucleoporins. They are generally believed to be the key constituents
      of the NPC permeability barrier. Comparison of the binding pattern of a transport
      receptor importin beta fragment, that binds specifically to FG-domains, with the
      binding pattern of wheat germ agglutinin that binds elsewhere in the NPC, reveals
      that FG-domains tend to cluster in the very center of the NPC. Furthermore, a
      controlled sequential release of the barrier-forming nucleoporins results in a
      gradual breakdown of the NPC permeability barrier. The breakdown is initiated by
      a dissociation of Nup62 from the NPC. This is accompanied by an increased passive
      diffusion of small molecules across the NPC. Subsequent dissociation of Nup98 and
      possibly other nucleoporins results in a collapse of the barrier for larger
      molecules. We therefore conclude that FG-nucleoporins do not contribute equally
      to the maintenance of the NPC permeability barrier exclusion limit. This implies
      that a controlled release of nucleoporins that contribute most to the formation
      and maintenance of the NPC barrier can facilitate access of therapeutic
      macromolecules into the nucleus.

PMID- 22386520
TI  - Squamous metaplasia in the cyst epithelium of type 1 congenital pulmonary airway
      malformation after thoracoamniotic shunt placement.
AB  - Thoracoamniotic shunting is the treatment of choice for management of the fetus
      with type 1 congenital pulmonary airway malformation. Thoracoamniotic shunting
      has been performed to reduce life-threatening risks such as fetal hydrops.
      However, caution is needed because of possible complications. Here, we report
      that thoracoamniotic shunting can cause histologic changes in the cyst epithelia.
      In 5 of 8 patients treated prenatally with thoracoamniotic shunting, squamous
      metaplasia in the cyst epithelia was seen; whereas squamous metaplasia was not
      found in 6 patients who were not treated with this procedure. Our results reveal
      that long-term exposure to the intrauterine environment could possibly lead to
      the change in the nature of cyst epithelium and consequent squamous metaplasia.

PMID- 22386521
TI  - Adenomas of the gallbladder. Morphologic features, expression of gastric and
      intestinal mucins, and incidence of high-grade dysplasia/carcinoma in situ and
      invasive carcinoma.
AB  - We report 201 gallbladder adenomas from 91 patients most of whom were adult
      females. Fifty-three (58%) patients had gallstones. In 83 (91%) patients the
      adenomas were single. One gallbladder had 102 adenomas. Histologically, 165 (82%)
      of 201 adenomas were classified as pyloric, 28 (14%) as intestinal, 5 (2.4%) as
      foveolar, and 3 (1.4%) as biliary. Two patients had intestinal-type adenomas
      coexisting with biliary papillomatosis. Twenty-eight percent of pyloric gland
      adenomas contained squamoid morules. Two pyloric gland adenomas were composed
      predominantly of columnar oxyphil cells. High-grade dysplasia/carcinoma in situ
      was identified in 44 (27%) of 165 pyloric gland adenomas and low-grade dysplasia
      in 25 (15%) of 165. However, only 2 (1%) invasive adenocarcinomas, both of
      intestinal type, arose in pyloric gland adenomas. Both patients survived more
      than 5 years. Intestinal-type adenomas were classified as tubular, papillary, and
      tubulopapillary. High-grade dysplasia/carcinoma in situ was recognized in 13
      (46%) of 28 intestinal adenomas. However, only 1 (3.5%) invasive adenocarcinoma
      with biliary phenotype arose in an intestinal-type adenoma. Foveolar adenomas
      showed low-grade dysplasia, and biliary adenomas were composed of columnar cells
      similar to the normal biliary cells of the gallbladder. None of these tumors
      progressed to adenocarcinoma. MUC5AC and MUC6 labeled 44 (95%) of 46 pyloric
      gland adenomas, whereas CDX2 was positive in 14 (78%) of 18 intestinal adenomas
      and MUC2 in 6 (33%) of 18. MUC5AC and MUC6 labeled 2 foveolar adenomas, and 2
      biliary adenomas expressed only CK7. The immunophenotype of gallbladder adenomas
      justifies their classification into pyloric, intestinal, foveolar, and biliary.
      Our results indicate that adenomas of the gallbladder play a minor role in the
      pathway of gallbladder carcinogenesis.

PMID- 22386522
TI  - An alternative technique for transosseous calcaneal pinning in external fixation.
AB  - The authors describe a technique in which two 5.5-mm pins are inserted from the
      posterior aspect of the calcaneus and advanced anteriorly on a slightly
      convergent vector. The 2 points of fixation, with a 5/8 ring, provide a "steering
      wheel" effect allowing for leverage and control of the hindfoot and ankle. The
      construct also allows for offloading of the posterior calcaneus.

PMID- 22386523
TI  - Good practices: the basis for evidence-based medicines.

PMID- 22386525
TI  - Association of depressive symptoms with inflammatory biomarkers among pregnant
      African-American women.
AB  - Depression and inflammation are associated with poorer birth outcomes. African
      American women have higher levels of inflammatory biomarkers, more depressive
      symptoms, and a disparate burden of poorer birth outcomes, but the association
      between depressive symptoms and inflammation within this higher-risk group is
      unknown. We examined this association among African-American women in the second
      trimester of pregnancy and additionally tested whether body mass index (BMI)
      mediates or moderates this relationship. We recruited 187 women from the
      obstetrics clinics of a large urban health system. Depression symptoms were
      measured with the Center for Epidemiological Studies Depression (CES-D) scale and
      inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP],
      interleukin [IL]-6, IL-10, IL-1beta, and tumor necrosis factor-alpha [TNF-alpha])
      with enzyme immunoassays. Multivariate regression models were fitted to determine
      the association between CES-D score and each inflammatory biomarker. CES-D was
      not associated with hs-CRP or TNF-alpha. CES-D was directly associated with IL
      1beta (P=0.03). BMI moderated the relationship between CES-D and IL-6 (P<0.01)
      and IL-10 (P=0.04); in leaner women, depressive symptoms were associated with
      higher IL-6 and IL-10 levels, whereas in heavier women, depressive symptoms were
      associated with lower IL-10 levels. BMI did not mediate the relationship between
      CES-D and inflammation. We conclude that depressive symptoms are associated with
      increased inflammation among pregnant African-American women. Future studies are
      needed to examine if depression, mediated through inflammation, increases the
      risk of adverse pregnancy outcomes in African-American women.

PMID- 22386524
TI  - Review of current and "omics" methods for assessing the toxicity (genotoxicity,
      teratogenicity and nephrotoxicity) of herbal medicines and mushrooms.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The increasing use of traditional herbal
      medicines around the world requires more scientific evidence for their putative
      harmlessness. To this end, a plethora of methods exist, more or less satisfying.
      In this post-genome era, recent reviews are however scarce, not only on the use
      of new "omics" methods (transcriptomics, proteomics, metabonomics) for
      genotoxicity, teratogenicity, and nephrotoxicity assessment, but also on
      conventional ones. METHODS: The present work aims (i) to review conventional
      methods used to assess genotoxicity, teratogenicity and nephrotoxicity of
      medicinal plants and mushrooms; (ii) to report recent progress in the use of
      "omics" technologies in this field; (iii) to underline advantages and limitations
      of promising methods; and lastly (iv) to suggest ways whereby the genotoxicity,
      teratogenicity, and nephrotoxicity assessment of traditional herbal medicines
      could be more predictive. RESULTS: Literature and safety reports show that
      structural alerts, in silico and classical in vitro and in vivo predictive
      methods are often used. The current trend to develop "omics" technologies to
      assess genotoxicity, teratogenicity and nephrotoxicity is promising but most
      often relies on methods that are still not standardized and validated.
      CONCLUSION: Hence, it is critical that toxicologists in industry, regulatory
      agencies and academic institutions develop a consensus, based on rigorous
      methods, about the reliability and interpretation of endpoints. It will also be
      important to regulate the integration of conventional methods for toxicity
      assessments with new "omics" technologies.

PMID- 22386526
TI  - The N-linked carbohydrate moiety of male reproductive tract CD52 (mrt-CD52)
      interferes with the complement system via binding to C1q.
AB  - Antisperm antibody detected in infertile female patients' sera has been shown to
      correlate with reduced fertility. The antibody showed strong complement-dependent
      cytotoxicity as determined by the sperm immobilization test (SIT). CD52 is a
      human glycosylphosphatidylinositol (GPI)-anchored antigen present in lymphocytes
      and male reproductive tracts (mrt), including mature sperm and seminal plasma.
      Recently, purified mrt-CD52 from human seminal plasma has been reported to
      interfere with the classical complement pathway, but not lectin binding or
      alternative pathways of the complement system. The purpose of this study is to
      determine which stage of the classical pathway mrt-CD52 regulates. mrt-CD52 was
      purified from human seminal plasma or intact sperm membrane. Immunoprecipitation
      assay was performed with the reaction of mrt-CD52, human complement and mAb H6
      3C4. Immunoprecipitate was formed by the carbohydrate moiety of mrt-CD52, but not
      by the GPI-anchor peptide. The C1q molecule (29 kDa) was detected in the
      immunoprecipitates by Western blotting analysis probed with anti C1q antibody,
      indicating that the carbohydrate moiety of mrt-CD52 binds to C1q. Also, the
      complement-dependent SIT revealed that purified CD52 inhibited sperm
      immobilization activity by antisperm antibody. These results suggest that mrt
      CD52 protects sperm function from complement attack if antisperm antibody is
      generated in the female reproductive tracts.

PMID- 22386527
TI  - Discovery of novel aminoquinazolin-7-yl 6,7-dihydro-indol-4-ones as potent,
      selective inhibitors of heat shock protein 90.
AB  - A novel class of Hsp90 inhibitors, structurally distinct from previously reported
      scaffolds, was developed from rational design and optimization of a compound
      library screen hit. These aminoquinazoline derivatives, represented by compound
      15 (SNX-6833) or 1-(2-amino-4-methylquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro
      1H-indol-4(5H)-one, selectively bind to Hsp90 and inhibit its cellular activities
      at concentrations as low as single digit nanomolar.

PMID- 22386528
TI  - Iodine-catalyzed condensation of isatin with indoles: a facile synthesis of
      di(indolyl)indolin-2-ones and evaluation of their cytotoxicity.
AB  - Isatin reacts smoothly with indoles in the presence of a catalytic amount of
      molecular iodine under mild conditions to afford a novel class of
      di(indolyl)indolin-2-one derivatives in good yields. These molecules are found to
      possess a promising cytotoxicity against cancer cells only but not on normal
      cells.

PMID- 22386529
TI  - From ApoA1 upregulation to BET family bromodomain inhibition: discovery of I
      BET151.
AB  - The discovery, synthesis and biological evaluation of a novel series of 7
      isoxazoloquinolines is described. Several analogs are shown to increase ApoA1
      expression within the nanomolar range in the human hepatic cell line HepG2.

PMID- 22386530
TI  - Lessons for circuit function from large insects: towards understanding the neural
      basis of motor flexibility.
AB  - Motor behaviors result from information processing that occurs in multiple neural
      networks acting at all levels from the initial selection of the behavior to its
      final generation. A long-standing research interest is how single neural networks
      can help generate different motor behaviors, that is, the origin of motor
      flexibility. Modern experimental techniques allow studying neural network
      activity during the production of multiple motor behaviors. Recent data provide
      strong evidence that the neural networks controlling insect legs are individually
      modified in task-dependent and finely tuned fashions. Understanding the
      mechanistic basis of these neural network modifications will be of particular
      interest in the upcoming years.

PMID- 22386531
TI  - Fanconi's anaemia and unilateral thumb polydactyly--don't miss it.
AB  - Fanconi's anaemia (FA) is a rare, life threatening inherited syndrome. Patients
      usually present late in the first decade of life with aplastic anaemia or acute
      myeloid leukaemia. FA children are also at high risk of solid organ tumours,
      anogenital squamous cancers, and endocrinopathies. These patients can present
      with unilateral radial abnormalities including thumb duplication. Hand surgeons
      can help achieve early diagnosis and improved survival in this group by early
      referral for screening. In a retrospective study of 202 children with radial ray
      anomalies seen over a 20 year period seven children had FA. Of these seven with
      FA, four had bilateral thumb hypoplasia and three had unilateral thumb anomalies-
      two unilateral thumb hypoplasias and one thumb duplication. The three children
      with unilateral anomalies were diagnosed late, presenting with bone marrow
      failure. All three have subsequently died following late bone marrow transplants.
      This study highlights the link between unilateral radial anomalies, including
      thumb duplication and FA and the importance of early genetic referral for
      diagnosis and surveillance.

PMID- 22386532
TI  - [Infantile hypophosphatasia].

PMID- 22386533
TI  - [Henoch-Schoenlein purpura: first manifestation of tuberculosis disease].

PMID- 22386534
TI  - [Mandibular aneurysmal bone cyst].

PMID- 22386535
TI  - [Use of the rapid antigen technique in the diagnosis of Streptococcus pyogenes
      pharyngotonsillitis].
AB  - INTRODUCTION: Streptococcus pyogenes is the most frequent bacterial cause of
      acute tonsillopharyngitis. The validity of the rapid antigen test was analysed
      for its diagnosis in a Paediatric Primary Care setting. The clinical profile with
      better diagnostic yield was also identified. The unnecessary use of antibiotics
      was quantified when the rapid antigen test or only the clinical diagnosis was
      used. The sensitivity of the assay to penicillin, erythromycin and clindamycin
      was also determined. PATIENTS AND METHODS: Cross-sectional study was conducted on
      children between 2 to 14 years with acute tonsillitis and/or pharyngitis seen in
      five Primary Care Centres, from January 2008 to May 2010. After a clinical
      diagnosis, two swabs were taken for pharyngotonsillar smears: the first was used
      for a rapid antigen test, and the second one for a culture and a study of
      antibiotic sensitivity, with its analysis being blind to the rapid test result. A
      total sample of 546 consecutive was envisaged and with consecutive sampling.
      RESULTS: A total 192 patients were included. The prevalence of Streptococcus
      pyogenes was 38.7% (95% CI: 31.4-45.7). Odynophagia and scarlatiniform rash were
      most likely with positive cultures, the Streptococcus pyogenes was sensitive to
      penicillin in 100%, to erythromycin in 97.3% and to clindamycin in 86.3%. The
      specificity of the rapid antigen test was 91.5% and with a Negative Predictive
      Value of 91.5%. About half (49.2%) of those who would have receive antibiotics
      for clinical suspicion would have been treated unnecessarily, with this
      decreasing to at least in 29.5% when using the rapid antigen test. CONCLUSIONS:
      The rapid antigen test can lead to a better use of antibiotics. Its use in
      Paediatric Primary Health Care could be useful when, as when the result is
      negative, there would be no need to confirm by a culture, in those Health Centres
      with difficult access to laboratory.

PMID- 22386536
TI  - Kinematic covariation in pediatric, adult and elderly subjects: is gait control
      influenced by age?
AB  - BACKGROUND: In human walking, kinematics of lower limb segments covary. Our
      objective was to assess the impact of age at different speeds (slow, medium and
      fast) on kinematic segmental covariation in normal subjects. METHODS: Thirty
      subjects ranged into 6 age groups ("5 years", "10 years", "15 years", "20 years"
      and "70 years") were included. We performed a gait analysis on a treadmill at 3
      predetermined speeds: 1 (slow), 3 (medium) and 5 (fast) km h(-1), except for the
      5 years group who was unable to walk at 5 km h(-1). Kinematic segmental
      covariation was computed and represented by a 3D-loop, described by a principal
      component analysis (Borghese's methodology). We studied the percentage of
      variance of each component of the principal component analysis, knowing that the
      percentage of variance of the first and the second components reflected the shape
      of the loop, and that the percentage of variance of the third component was an
      index of its planarity. The effect of age was tested using a one-way analysis of
      variance. FINDINGS: When comparing the age groups at the same speed, we found a
      significant difference in the percentage of variance of the first and the second
      components between the 5 and the 10 years at 3 km h(-1). We also noticed a
      difference in the percentage of variance of the third component at 5 km h(-1)
      between the 10 years and the 15 and 20 years groups. INTERPRETATION: We observed
      that kinematic covariation remains stable throughout adulthood between 15 and 70
      years old at slow, medium and fast speed. In children, a mature percentage of
      variance of the first and the second components is acquired from 10 years old and
      a mature percentage of variance of the third component from 15 years old.

PMID- 22386538
TI  - Patient decision aids in knee replacement surgery.
AB  - Arthroplasty is an effective intervention for symptomatic knee osteoarthritis
      refractory to conservative therapy. However, recent data highlights regional
      variations in service provision unrelated to disease severity and a low, but not
      insignificant, rate of patient dissatisfaction. The variation in knee
      arthroplasty provision is in part also due to the clinical decision-making of
      orthopaedic surgeons. The management of osteoarthritis is an example of a
      preference-sensitive clinical pathway, and possible explanations for poor patient
      satisfaction include unrealistic expectations and poor perception of potential
      benefits and risks. In addition to the individual impact, this represents an
      inefficient use of resources by healthcare providers during a challenging
      economic period. Improved shared-decision making between patients and clinicians
      would potentially address these issues. Patient decision aids provide relevant
      personalized evidence-based information to facilitate the shared decision-making
      process. Orthopaedic surgeons are receptive to the use of patient decision aids
      to support shared decision-making, but there are a number of issues to overcome
      before they are routinely adopted. The number of decision aids and the literature
      supporting their effectiveness is growing rapidly. NHS Direct has launched online
      patient decision support for knee osteoarthritis. The use of patient decision
      aids in clinical practice is gathering pace and may soon become the ethical and
      legal standard. This article provides a narrative review of patient decision aids
      in the context of knee replacement surgery from a UK perspective.

PMID- 22386537
TI  - Superantigen-induced CD4 memory T cell anergy. I. Staphylococcal enterotoxin B
      induces Fyn-mediated negative signaling.
AB  - Memory CD4 T cells must provide robust protection for an organism while still
      maintaining self-tolerance. Superantigens reveal a memory cell-specific
      regulatory pathway, by which signaling through the TCR can lead to clonal
      tolerance (anergy). Here we show that the src kinase Fyn is a critical regulator
      of anergy in murine memory CD4 T cells induced by the bacterial superantigen
      staphylococcal enterotoxin B (SEB). Exposure to SEB results in impaired TCR
      signaling due to failed CD3/ZAP-70 complex formation. Further, signal
      transduction through the TCR remains similarly blocked when anergic memory cells
      are subsequently exposed to agonist peptide antigen. Pharmacological inhibition
      or genetic elimination of Fyn kinase reverses memory cell anergy, resulting in
      SEB-induced cell proliferation. The mechanism underlying impaired TCR signaling
      and subsequent memory cell anergy must involve a Fyn signaling pathway given that
      the suppression of Fyn activity restores CD3/ZAP-70 complex formation and TCR
      proximal signaling.

PMID- 22386539
TI  - [One patient, one mutation and two cardiomyopathies - hypertrophic cardiomyopathy
      and left ventricular noncompaction].

PMID- 22386540
TI  - [Cardio-defibrillator with an additional subcutaneous electrode shock].

PMID- 22386541
TI  - Variations of nursing teamwork by hospital, patient unit, and staff
      characteristics.
AB  - The aim of this cross-sectional study was to examine the relationship among
      hospital, patient units, and staff characteristics and nursing teamwork. Using
      multiple linear regression analysis, we found that nursing role, shift,
      absenteeism, perceived adequacy of staffing, and unit type were significant
      predictors of teamwork.

PMID- 22386542
TI  - Contraception and pregnancy in microbicide trials.
AB  - The distinctive feature of the human immunodeficiency virus (HIV) epidemic in Sub
      Saharan Africa is the burden on women, in particular young women of reproductive
      age. Consequently, most late-phase effectiveness microbicide clinical trials are
      conducted in sub-Saharan Africa where fertility rates are high. Because late
      phase clinical trials are conducted over prolonged periods of time, women
      participating in these trials may fall pregnant during the trial. Their unborn
      babies may be exposed to a drug whose teratogenic potential is unknown if the
      investigational drug is not withdrawn. High pregnancy rates in such trials may
      compromise statistical integrity, as women will be withdrawn from the study drug
      for the duration of the pregnancy. It is therefore imperative for microbicide
      trials to implement effective contraceptive and pregnancy management programmes
      that maintain low pregnancy rates and the safety of unborn babies while not
      compromising the conduct and statistical integrity of the trial.

PMID- 22386544
TI  - Intramedullary fixation of the medial column of the foot with a solid bolt in
      Charcot midfoot arthropathy: a case report.
AB  - Medial column fixation for rocker-bottom deformity in Charcot arthropathy is
      commonly performed. However, implant failure is commonly encountered because of
      uncontrolled weight bearing by the patient. The aim of this case report is to
      describe the use of a large solid bolt for fusion of the medial column of the
      foot in a patient with collapse of the midfoot due to diabetic neuroarthropathy.

PMID- 22386545
TI  - Arthroscopic ulnar nerve decompression in the setting of elbow osteoarthritis.
AB  - PURPOSE: To present the technique and outcomes of arthroscopic ulnar nerve
      decompression at the elbow in a series of patients with associated
      osteoarthritis. METHODS: A retrospective chart review identified all patients
      with symptomatic ulnar compression neuropathy and osteoarthritis at the elbow
      treated with arthroscopic decompression between March 2002 and June 2007.
      Information regarding preoperative symptom severity and function, associated
      arthritis and other disorders of the involved extremity, postoperative symptoms
      and function, complications, and reoperations were reviewed from the medical
      record. All patients were followed up for at least 12 months, and data collection
      included clinical evaluations and survey correspondence. RESULTS: Thirteen
      patients (15 elbows) were available for review. The series consisted of patients
      with an average age of 51 years (range, 20-75 y). All patients had arthroscopic
      ulnar nerve decompression, osteophyte resection, and capsulectomy during the same
      procedure. An average postoperative follow-up of 47 months revealed 7 excellent,
      5 good, 1 fair, and 2 poor results. Three patients had reoperations because of
      persistent or recurrent symptoms. These 3 patients had severe (Dellon
      classification) symptoms including muscular wasting on presentation. CONCLUSIONS:
      This technique appears to be a useful procedure for treatment of cubital tunnel
      syndrome at the time of elbow arthroscopic debridement arthroplasty. Additional
      follow-up and prospective comparative studies are indicated to further evaluate
      this technique. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22386546
TI  - The effect of botulinum neurotoxin-A on blood flow in rats: a potential mechanism
      for treatment of Raynaud phenomenon.
AB  - PURPOSE: Botulinum neurotoxin-A (BoNTA) is used to treat several disorders,
      including Raynaud phenomenon. Recent investigations cite toxin-induced increases
      in blood flow, but no mechanism for BoNTA's actions is proposed. This study
      hypothesized that local application of BoNTA causes arteriolar vasodilation
      through sympathetic blockade and results in increased blood flow. METHODS:
      Microvascular effects of BoNTA were assessed using a rat cremaster preparation.
      Cremaster microvascular diameters were measured in the muscle before and after
      treatment with the muscle paralytic agent gallamine triethiodide. Preparations
      were then treated with one of the following: BoNTA (4, 6, or 10 units), BoNTA
      dilution vehicle, or denatured BoNTA. Arteriolar diameters were measured
      repeatedly over the observation period. Additional preparations were treated with
      either tetrodotoxin or prazosin and rauwolscine before BoNTA to confirm that the
      observed vasodilatory responses were the result of sympathetic neural inhibition.
      RESULTS: The BoNTA application resulted in a significant dose-dependent
      vasodilation (13% to 15%) of observed cremaster arterioles. Control treatments
      did not cause vasodilation. Both tetrodotoxin and prazosin/rauwolscine treatments
      elicited similar vasodilatory effects, with no additional vasodilation elicited
      by BoNTA. Addition of sodium nitroprusside following BoNTA elicited further
      vasodilation. In addition, systemic arterial pressure was unaffected by the local
      administration of BoNTA. CONCLUSIONS: Local application of BoNTA results in
      arteriolar dilation that yields an approximate 69% increase in blood flow,
      without changing systemic arterial pressure. A BoNTA-mediated vasodilation
      through sympathetic blockade is a likely mechanism to explain the increase in
      blood flow reported after treatment with the toxin. CLINICAL RELEVANCE: The
      ability of BoNTA to inhibit sympathetic nervous input reduces vasoconstriction,
      which is the most likely mechanism for improvement seen in Raynaud phenomenon
      patients following BoNTA injection.

PMID- 22386547
TI  - Opening wedge trapezial osteotomy as possible treatment for early
      trapeziometacarpal osteoarthritis: a biomechanical investigation of radial
      subluxation, contact area, and contact pressure.
AB  - PURPOSE: Radial subluxation and cartilage thinning have been associated with
      initiation and accelerated development of osteoarthritis of the
      trapeziometacarpal joint. Few investigators have reported on the benefits of
      opening wedge trapezial osteotomy for altering the contact mechanics of the
      trapeziometacarpal joint as a possible deterrent to the initiation or progression
      of osteoarthritis. We used cadaveric specimens to determine whether opening wedge
      osteotomy of the trapezium was successful in reducing radial subluxation of the
      metacarpal base and to quantify the contact area and pressure on the trapezial
      surface during simulated lateral pinch. METHODS: We used 8 fresh-frozen specimens
      in this study. The flexor pollicis longus, abductor pollicis longus, adductor
      pollicis, abductor pollicis brevis, and flexor pollicis brevis/opponens pollicis
      tendons were each loaded to simulate the thumb in lateral pinch position. We
      measured radial subluxation from anteroposterior radiographs before and after
      placement of a 15 degrees  wedge. We used real-time sensors to analyze contact
      pressure and contact area distribution on the trapezium. RESULTS: Center of force
      in the normal joint under lateral pinch loading was primarily located in the
      dorsal region of the trapezium. After wedge placement, contact pressure increased
      in the ulnar-dorsal region by 76%. Mean contact area increased in the ulnar
      dorsal region from 0.05 to 0.07 cm(2), and in the ulnar-volar region from 0.003
      to 0.024 cm(2). The average reduction in joint subluxation was 64%. CONCLUSIONS:
      The 15 degrees  opening wedge osteotomy of the trapezium reduced radial
      subluxation of the metacarpal on the trapezium and increased contact pressure and
      contact area away from the diseased compartments of the trapezial surface.
      Trapezial osteotomy addresses the 2 preeminent theories about the initiation and
      progression of osteoarthritis. CLINICAL RELEVANCE: By reducing radial subluxation
      and altering contact pressure and contact area, trapezial osteotomy may prove an
      alternative to first metacarpal extension osteotomy or ligament reconstruction in
      early stages of degenerative arthritis of the trapeziometacarpal joint.

PMID- 22386548
TI  - Effects of tension across the tendon repair site on tendon gap and ultimate
      strength.
AB  - PURPOSE: Tendons repaired with varying amounts of tension result in different
      degrees of shortening of the tendon segment within core sutures, which may affect
      tensile strengths. We aimed to investigate the effects of tension across the
      repair site on gap formation forces and ultimate strength. METHODS: Fifty-seven
      porcine flexor tendons were repaired with a 2-strand modified Kessler repair or a
      4-strand cross-lock repair. For each type of repair, the tendons were divided
      into 3 groups: by 0%, 10%, or 20% shortening of tendon segment encompassed within
      core sutures. The repaired tendons had a single load-to-failure test in a
      materials testing machine. The forces required for initial and 2-mm gap formation
      and ultimate failure were recorded and statistically compared for each group.
      RESULTS: With either 2-strand or 4-strand repair, the tendons in the 10% tendon
      segment shortening group withstood significantly higher initial and 2-mm gap
      formation forces than those in the group with no shortening, with average
      increases of 5 to 10 N after 10% shortening. Increasing the tendon-segment
      shortening to 20% produced a slight increase in the initial and 2-mm gap forces
      compared with those with 10% shortening, which was statistically significant only
      in the tendons with the 4-strand repair. The ultimate strengths were not
      significantly different among the tendons with either 2-strand or 4-strand repair
      of any degrees of shortening. CONCLUSIONS: Tensioning the core suture to shorten
      its encompassed tendon segment by 10% substantially increases resistance to
      postoperative gapping. Further tensioning to produce 20% shortening of the tendon
      segment increased the gapping forces by a much smaller amount. This study
      suggests that a slightly tensioned surgical repair, shortening the encompassed
      tendon segment by approximately 10%, is appropriate. CLINICAL RELEVANCE: Slightly
      tensioning core sutures across the tendon repair site, such as adding tension to
      cause 10% tendon-segment shortening, would greatly increase the gap resistance of
      the surgical repair.

PMID- 22386549
TI  - Radiation therapy for infiltrative giant cell tumor of the tendon sheath.
AB  - PURPOSE: Giant cell tumor of the tendon sheath (GCTTS) has a high recurrence
      after excision and can be a management challenge. Although experience with
      radiation therapy for GCTTS is limited, it is purported to control infiltrative
      cases and prevent recurrence. We describe our approach to primary and recurrent
      GCTTS, as well as our identification of infiltrative cases and their treatment
      with radiation therapy. METHODS: We reviewed 58 patients (32 men and 26 women)
      with GCTTS in the hand excised at 1 center between 1998 and 2009. Mean age at the
      time of excision at our center was 50 years. A total of 14 patients who had
      undergone primary excision at other centers were referred to our center with
      recurrent disease. Intraoperatively, we found infiltrative disease in 4 patients
      undergoing primary excision at our center and in 10 of the 14 patients referred
      to our institution with recurrent disease. All infiltrative (4 primary and 10
      recurrent) cases were referred for radiation therapy. RESULTS: Of 14 patients
      with infiltrative tumors, 10 received radiation therapy (3 patients declined and
      1 had a major comorbidity that precluded therapy). Radiation dose was either 35
      Gy in 14 fractions or 48 Gy in 24 fractions. At 3.1 years' follow-up, none of the
      10 patients treated with radiation therapy had recurrence. No long-term
      complications were associated with radiation therapy, and hand function was not
      adversely affected. We identified 4 recurrences, 2 of which were in patients with
      primary tumors without infiltrative features. Of the 4 patients who were referred
      for radiation but did not receive it, 2 patients developed recurrence by 2 years
      after referral. CONCLUSIONS: In cases of infiltrative GCTTS, radiation therapy
      may provide local tumor control with preservation of hand function. Radiation
      therapy may be particularly helpful when further surgery is not a good option.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22386550
TI  - Evaluation of superficial and deep self-inflicted wrist and forearm lacerations.
AB  - PURPOSE: Self-inflicted wrist or forearm laceration is a specific type of injury
      presenting to emergency departments. Many investigators have described wrist
      cutting from a psychiatric viewpoint. We hypothesized that the character of
      patients with deep wounds is different from those with superficial wounds. We
      investigated patients who cut their wrist or forearms as an act of self
      mutilation from the viewpoint of wound severity. METHODS: We reviewed 31 patients
      with self-inflected wrist injuries who were treated in our medical center from
      2004 through 2009. We divided them into 2 groups: deep (15 patients) and
      superficial (16 patients). We investigated differences in age and gender, sites
      of self-cutting, frequency of self-injury attempts, object used for wrist
      cutting, group psychiatric parameters, required wound treatments, and psychiatric
      history and follow-up. RESULTS: Younger patients were more likely to have injured
      themselves severely compared with older patients. Differences in clinical
      findings between deep and superficial injury groups included the following: (1)
      all male patients had deep injuries; (2) patients with superficial wounds were
      more likely to have cut themselves previously; (3) patients in the deep injury
      group tended to injure themselves at multiple sites; (4) patients in the deep
      injury group tended to perform self-cutting with any sharp-edged object at hand;
      (5) 50% of our patients had received no psychiatric care before being seen by us
      for their injury; and (6) one-third discontinued the psychiatric treatment
      prematurely. CONCLUSIONS: There are differences between patients who perform self
      inflicted deep versus superficial wrist cutting. We also found that the ages and
      psychiatric diagnoses of our patients differed from previous reports. This is
      likely because the available literature includes only patients who received
      psychiatric care. We found that 50% of our patients had received no psychiatric
      care, which highlights the importance of hand surgeons treating these patients to
      initiate psychiatric consultation.

PMID- 22386551
TI  - Surgical and nonsurgical treatment of cubital tunnel syndrome in pediatric and
      adolescent patients.
AB  - PURPOSE: Few studies have investigated the presence or treatment of cubital
      tunnel syndrome in pediatric or adolescent patients. We conducted this
      retrospective investigation to quantify success rates of nonsurgical care and to
      assess patient outcomes after surgical intervention. METHODS: We identified 39
      extremities treated for cubital tunnel syndrome between 2000 and 2009 at one
      institution. We documented patient demographic data, precipitating events,
      symptomatology, physical examination findings, and treatment for all patients. We
      assessed patient-rated outcomes with validated measures including the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the visual
      analog scale (VAS). RESULTS: Subjective complaints at the time of presentation
      included 16 extremities with ulnar nerve instability at the elbow, 21 extremities
      with pain at the elbow, and 15 extremities with numbness and tingling in the ring
      and small fingers. Physical examination revealed 33 extremities with a positive
      Tinel sign and 20 extremities with a positive elbow flexion-compression test. In
      the nonsurgical group (9), pretreatment DASH scores averaged 32 and posttreatment
      DASH scores averaged 11. Pretreatment recall VAS pain scores had a median of 7,
      and were similar to posttreatment scores, which had a median of 3. In the
      surgical group (30), DASH scores averaged 46 before surgery and improved to 7 at
      final follow-up. The VAS pain scores improved from a median of 8 before surgery
      to 2 after surgery. A total of 30 patients (from both groups) were treated with a
      trial of nonsurgical care without symptom resolution. CONCLUSIONS: Cubital tunnel
      syndrome in pediatric or adolescent patients is rare. It can be treated
      successfully with surgical intervention. Although nonsurgical treatment is
      unlikely to relieve symptoms in this patient population, a trial of nighttime
      splinting, activity modification, and anti-inflammatory medications remains
      appropriate for most patients. Surgical intervention is effective for symptom
      relief if nonsurgical care fails. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      III.

PMID- 22386552
TI  - Flexor tenosynovial fistulas in the palm.
AB  - PURPOSE: Tenosynovial fistulas in the palm are rare. If conservative treatment is
      unsuccessful, surgical treatment may include excision of the fistula and local
      flap coverage. In this article, I report 15 patients who were surgically treated
      for tenosynovial fistulas in the palm. METHODS: Between 1996 and 2009, I treated
      15 patients for tenosynovial fistulas in the palm. There were 9 women and 6 men,
      with an average age of 42 years (range, 21-63 y). The index finger was involved
      in 5 patients, the long finger in 7, and the ring finger in 3. One patient had a
      fish fin injury, 6 had multiple surgeries for release of stenosing flexor
      tenosynovitis with intraoperative steroid injections, 1 had a pellet gun injury,
      and 7 had lacerations in the distal palm. Four patients had had unsuccessful
      closure of the fistula. All patients presented with a distal palm sinus draining
      clear frothy fluid. There were no signs of infection. Gram stains and cultures
      were negative. Smear and culture for Mycobacterium marinum were negative in the
      patient who had the fish fin injury. I tried conservative treatment in all
      patients for an average of 7 weeks. All patients were treated with excision of
      the sinus tract with partial resection of the A1 pulley and soft tissue coverage
      with a transposition flap. Pathological examination revealed epithelialization
      with nonspecific chronic inflammation. RESULTS: Postoperative follow-up averaged
      59 months (range, 6-148 mo). All fistulas healed. Patients regained full range of
      motion and normal grip and pinch strength. One patient had transient tenderness
      of the scar for 3 months. There were no recurrences. CONCLUSIONS: Tenosynovial
      fistulas may develop after an injury to the flexor tendon sheath or following the
      use of steroids after release of trigger fingers recurring after an initial
      surgical release. Surgical treatment with excision of the fistula and local flap
      coverage yields excellent results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 22386553
TI  - Pharmacologic management of myxomatous mitral valve disease in dogs.
AB  - Myxomatous mitral valve disease (MMVD) causing mitral regurgitation is the most
      important disease of the heart in small animal cardiovascular medicine. Because
      MMVD is an example of a chronic disease that progresses from mild to severe over
      years, treatment strategies change with the stage of the disease. In this review
      the treatment options are compared and contrasted as they are discussed relative
      to the recently published ACVIM consensus statement regarding the treatment of
      MMVD. Results from clinical trials and evidence-based medicine are likely to
      provide significant improvements in the management of MMVD in the coming decades.

PMID- 22386554
TI  - Symptoms in the cancer patient: of importance for their caregivers' quality of
      life and mental health?
AB  - PURPOSE: To examine the level of symptom burden in a sample of cancer patients in
      a curative and palliative phase. In addition to determine a) whether the
      patients' symptom burden and patients' demographic variables, and b) the
      caregivers' demographic variables' impact on the caregivers' quality of life and
      mental health. METHOD: This descriptive, cross-sectional study combines data from
      two samples. The first group consists of caregivers of hospitalized patients with
      cancer in the late palliative phase and the second group is caregivers of
      outpatients with cancer who have pain and/or use of analgesics. RESULTS: The main
      result showed that the symptom burden was close to equal when we compared the
      cancer patients in the palliative and the curative phase respectively. The whole
      sample of patients seemed extremely tired because they scored high on items
      capturing fatigue or weakness. They also had problems with pain and constipation.
      For patients having trouble sleeping, the caregivers' reported higher level of
      depression, whilst caregivers' gender had impact on the caregivers' anxiety. The
      younger the patients the more the impact on caregivers' QOL mental health.
      CONCLUSION: In this study no significant differences were revealed when comparing
      symptom burden among cancer patients in different stages of the disease.
      Caregivers reported more depression when patients had trouble sleeping and more
      declined mental quality of life when patients were younger. Female caregivers
      reported more anxiety than male caregivers.

PMID- 22386555
TI  - Injuries complicating musical practice and performance: the hand surgeon's
      approach to the musician-patient.

PMID- 22386556
TI  - The Linburg-Comstock anomaly: incidence in Malaysians and effect on pinch
      strength.
AB  - PURPOSE: To obtain epidemiologic data on the Linburg-Comstock anomaly in Malaysia
      and to study the effect of the anomaly on key pinch strength. METHODS: We
      examined 292 healthy subjects (162 female and 130 male) bilaterally for the
      presence of the Linburg-Comstock anomaly. Each subject's key pinch strength was
      measured bilaterally using a pinch meter. RESULTS: The Linburg-Comstock anomaly
      was present in 101 of the 292 subjects (35%). Sixty-five subjects (22%) had it
      unilaterally, and 36 subjects (6%) had it bilaterally. The anomaly was associated
      with superior key pinch strength. CONCLUSIONS: The study provides epidemiologic
      data of this anomaly in Malaysia and considers its anatomical influence on key
      pinch strength. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

PMID- 22386557
TI  - Use of standard and anatomic-tilt lateral X-rays to determine distal radius volar
      angulation.
AB  - PURPOSE: To determine the reliability of measurements of distal radius volar tilt
      using either standard lateral or anatomic tilt lateral (ATL) radiographs, and to
      compare the mean values obtained using each radiographic method. METHODS: We
      obtained standard and 23 degrees  ATL plain radiographs of the distal radii of 20
      patients with a distal radius fracture treated with a volar locking plate, and of
      20 healthy individuals without a history of fracture of the wrist. Three
      orthopedic surgeons measured volar tilt twice with an interval of 4 weeks. We
      analyzed intraobserver and interobserver reliability and compared intraobserver
      means of volar tilts obtained using standard and ATL radiographs. RESULTS: The
      volar tilts measured using ATL radiographs in patients and healthy controls
      showed moderate to excellent intraobserver and interobserver reliability, whereas
      those determined using standard lateral radiographs showed poor to moderate
      intraobserver and interobserver reliability in patients and controls. However,
      the mean values of volar tilts measured in standard lateral radiographs and in
      ATL radiographs were similar in patients and not significantly different in
      healthy controls. CONCLUSIONS: Volar tilt measurements obtained using anatomic
      tilt lateral radiographs provided moderate to excellent reliability. However, we
      found no statistically significant difference between volar tilts determined
      using ATL and standard lateral radiographs. Accordingly, standard lateral and ATL
      radiographs are interchangeable with respect to volar tilt measurements. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 22386558
TI  - Lateral antebrachial cutaneous neuropathy following the long head of the biceps
      rupture.
AB  - Lateral antebrachial cutaneous neuropathies present as purely sensory lesions,
      manifesting as elbow pain or dysesthetic pain over the lateral forearm.
      Classically, entrapment of the lateral antebrachial cutaneous nerve has been
      documented at the lateral edge of the biceps tendon as it exits the deep fascia
      in the antecubital fossa. We report a case of lateral antebrachial cutaneous
      nerve traction neuritis, rather than entrapment, resulting from a rupture of the
      long head of the biceps. The biceps displaced the nerve laterally, resulting in
      sensory loss and severe allodynia. The patient's symptoms were relieved with
      proximal biceps tenodesis.

PMID- 22386559
TI  - Percutaneous screw and axial Kirschner wire fixation for acute transscaphoid
      perilunate fracture dislocation.
AB  - PURPOSE: In this retrospective, nonrandomized study, we evaluated the clinical
      outcomes of percutaneous screw and K-wire fixation in the treatment of acute
      transscaphoid perilunate fracture dislocation. METHODS: Between 2004 and 2009, we
      studied 24 patients treated by fixation with a 2.0-mm (0.078-in) axial K-wire
      across the capitolunate joint and a percutaneous screw (3.0-mm AO cannulated
      screws were used in 13 patients, and Herbert-Whipple screws were used in 11
      patients) within 7 days of the injury. We performed a comparative radiographic
      assessment of the scapholunate angle, radiolunate angle, capitolunate angle,
      revised carpal height ratio, and gap between the scapholunate joint between the
      injured wrist and the contralateral, healthy wrist. Clinical outcomes were
      evaluated on the basis of range of motion, pain, functional status, and Mayo
      scores. RESULTS: Twenty-three patients (96%) achieved scaphoid union at a mean
      union time of 18 weeks (range, 14-28 wk). Radiographic assessments revealed no
      statistically significant difference between the injured wrist and the
      contralateral, healthy wrist. However, significant differences were noted in the
      mean range of motion during flexion and forearm supination between the injured
      wrist and contralateral healthy wrist. The mean wrist function results were
      encouraging, and the average Mayo score was 83. CONCLUSIONS: A percutaneous
      procedure involving screw fixation for the scaphoid fracture and an axial K-wire
      fixation for intercarpal dislocation is a successful treatment for acute
      transscaphoid perilunate fracture dislocation. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic III.

PMID- 22386560
TI  - Photochemical mechanisms of light-triggered release from nanocarriers.
AB  - Over the last three decades, a handful of photochemical mechanisms have been
      applied to a large number of nanoscale assemblies that encapsulate a payload to
      afford spatio-temporal and remote control over activity of the encapsulated
      payload. Many of these systems are designed with an eye towards biomedical
      applications, as spatio-temporal and remote control of bioactivity would advance
      research and clinical practice. This review covers five underlying photochemical
      mechanisms that govern the activity of the majority of photoresponsive
      nanocarriers: 1. photo driven isomerization and oxidation, 2. surface plasmon
      absorption and photothermal effects, 3. photo driven hydrophobicity changes, 4.
      photo driven polymer backbone fragmentation and 5. photo driven de-crosslinking.
      The ways in which these mechanisms have been incorporated into nanocarriers and
      how they affect release are detailed, as well as the advantages and disadvantages
      of each system.

PMID- 22386561
TI  - Microsystems technologies for drug delivery to the inner ear.
AB  - The inner ear represents one of the most technologically challenging targets for
      local drug delivery, but its clinical significance is rapidly increasing. The
      prevalence of sensorineural hearing loss and other auditory diseases, along with
      balance disorders and tinnitus, has spurred broad efforts to develop therapeutic
      compounds and regenerative approaches to treat these conditions, necessitating
      advances in systems capable of targeted and sustained drug delivery. The delicate
      nature of hearing structures combined with the relative inaccessibility of the
      cochlea by means of conventional delivery routes together necessitate significant
      advancements in both the precision and miniaturization of delivery systems, and
      the nature of the molecular and cellular targets for these therapies suggests
      that multiple compounds may need to be delivered in a time-sequenced fashion over
      an extended duration. Here we address the various approaches being developed for
      inner ear drug delivery, including micropump-based devices, reciprocating
      systems, and cochlear prosthesis-mediated delivery, concluding with an analysis
      of emerging challenges and opportunities for the first generation of technologies
      suitable for human clinical use. These developments represent exciting advances
      that have the potential to repair and regenerate hearing structures in millions
      of patients for whom no currently available medical treatments exist, a situation
      that requires them to function with electronic hearing augmentation devices or to
      live with severely impaired auditory function. These advances also have the
      potential for broader clinical applications that share similar requirements and
      challenges with the inner ear, such as drug delivery to the central nervous
      system.

PMID- 22386562
TI  - Metabolomics-based component profiling of hard and semi-hard natural cheeses with
      gas chromatography/time-of-flight-mass spectrometry, and its application to
      sensory predictive modeling.
AB  - Gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS) was used to
      analyze hydrophilic low molecular weight components, including amino acids, fatty
      acids, amines, organic acids, and saccharides, in cheese, and the sensometric
      application for practical metabolomic studies in the food industry is described.
      Derivatization of target analytes was conducted prior to the GC/TOF-MS analysis.
      Data on 13 cheeses, six Cheddar cheeses, six Gouda cheeses and one Parmigiano
      Reggiano cheese, were analyzed by multivariate analysis. The uniqueness of the
      Parmigiano-Reggiano cheese metabolome was revealed. Principal component analysis
      (PCA) showed no grouping of the Cheddar cheeses and Gouda cheeses according to
      production method or country of origin. The PCA loading plot confirms that many
      amino acids contribute positively to PC1, suggesting that PC1 is closely related
      to degradation of proteins, and that lactic acid contributed positively to PC2,
      whereas glycerol contributed negatively to PC2, suggesting that factors regarding
      degradation of carbohydrates and fats were expressed in PC2. Partial least
      squares (PLS) regression models were constructed to predict the relationship
      between the metabolite profile and two sensory attributes, "Rich flavor" and
      "Sour flavor", which were related to maturation. The compounds that play an
      important role in constructing each sensory prediction model were identified as
      12 amino acids and lactose for "Rich flavor", and 4-aminobutyric acid, ornithine,
      succinic acid, lactic acid, proline and lactose for "Sour flavor". The present
      study revealed that metabolomics-based component profiling, focusing on
      hydrophilic low molecular weight components, was able to predict the sensory
      characteristics related to ripening.

PMID- 22386563
TI  - Lymphatic microvessel density combined with CT used in the diagnosis of
      mediastinal and hilar lymph node metastasis of non-small cell lung cancer.
AB  - BACKGROUND AND AIMS: Lymphatic microvessel density (LMVD) has been demonstrated
      to correlate with tumor metastasis. The purpose of this study is to determine
      whether the criteria combining LMVD with computed tomography (CT) could improve
      the diagnostic accuracy of lymph node (LN) metastasis in non-small cell lung
      cancer (NSCLC). METHODS: Ninety four patients with NSCLC who had chest CT scans
      preoperatively and LMVD tested by immunohistochemistry postoperatively were
      randomized into two groups: the training set (n = 66) and the test set (n = 28).
      Cut-off point of LMVD was selected to separate the LN metastasis-predictive
      positive and negative groups. On the basis of LMVD levels, chest CTs of the
      training set were re-analyzed and hypothetical criteria for LN metastasis
      diagnosis were established. Diagnostic characteristics for LN metastasis were
      tested by using the combined criteria in the test set as compared to those of CT
      alone. RESULTS: There was a significantly positive correlation between LMVD and
      LN metastasis (p <0.01). For sensitivity, specificity, positive predictive value
      (PPV) and negative predictive values (NPV), accuracy was 67, 81, 75, 81 and 79%
      for the combined criteria, respectively. Diagnostic efficacy of the combined
      criteria was significantly higher than that of CT only (p <0.05). CONCLUSIONS:
      Diagnosis of LN metastasis using a combination of LMVD and CT is superior to the
      CT-only diagnosis. In future clinical trials, it is necessary to evaluate the
      efficacy of adjuvant therapy for the selection of patients according to the
      combined criteria.

PMID- 22386564
TI  - Optimization of the aromatase inhibitory activities of pyridylthiazole analogues
      of resveratrol.
AB  - Aromatase is an established target not only for breast cancer chemotherapy, but
      also for breast cancer chemoprevention. The moderate and non-selective aromatase
      inhibitory activity of resveratrol (1) was improved about 100-fold by replacement
      of the ethylenic bridge with a thiadiazole and the phenyl rings with pyridines
      (e.g., compound 3). The aromatase inhibitory activity was enhanced over 6000-fold
      by using a 1,3-thiazole as the central ring and modifying the substituents on the
      'A' ring to target the Met374 residue of aromatase. On the other hand, targeting
      the hydroxyl group of Thr310 by a hydrogen-bond acceptor on the 'B' ring did not
      improve the aromatase inhibitory activity.

PMID- 22386565
TI  - Integrated structure-based activity prediction model of benzothiadiazines on
      various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in
      the discovery of new derivatives.
AB  - This work presents the first structure-based activity prediction model for
      benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and
      4).The model is a comprehensive workflow of structure-based field template
      followed by guided docking. The field template was used as a pre-filter and a
      tool to provide hits in good orientation and position. It was created based on
      detailed molecular interaction field analysis which includes Topomer CoMFA, grid
      independent analysis and Superstar. On the other hand, Guided docking was used as
      a refinement and assessment tool. It was actively directed by two scores: Moldock
      score as an interaction descriptor (r(2)=0.65) and a template similarity score as
      a measure for accurate binding-mode compliance. The docking template was based on
      energy-based pharmacophore analysis. The whole procedure was formulated and
      tweaked for both screening (ROC of AUC=0.91) and activity prediction (r(2) of
      0.8) for the genotype 1a. In order to widen the model scope, linear interaction
      energy was used as a tool for predicting activities of other genotypes based on
      the docked ligand poses while mutation binding energy was used to investigate the
      effect of each amino acid mutation in genotype 4. The model was applied for
      structure-based fragment hopping by screening a library designed by reaction
      enumeration. A top scoring hit was used to generate a focused library such that
      it has lower TPSA than the original class ligands and thus better pharmacokinetic
      properties. After that, experimental validation was carried out by the synthesis
      of this library and its biological evaluation which yielded compounds that
      exhibit EC(50) ranging from 1.86 to 23 MUM.

PMID- 22386566
TI  - Exploring the role of obsessive-compulsive relevant self-worth contingencies in
      obsessive-compulsive disorder patients.
AB  - This article examines whether self-worth contingencies in the personal domains of
      cleanliness, morality, hoarding, certainty, accuracy, religion and respect for
      others have specific associations with obsessive symptoms and cognitions in
      individuals with obsessive-compulsive disorder (OCD). Fifty-seven patients with a
      primary diagnosis of OCD completed the Obsessional Concerns and Self
      Questionnaire (OCSQ), designed to assess the extent to which respondents consider
      OCD content domains relevant to their self-worth, along with a battery of other
      instruments. Results indicate that the OCSQ is more associated with OCD than with
      non-OCD anxiety symptoms, and that it is also associated with comorbid depressive
      symptoms in OCD patients. Moreover, the OCSQ-Order and Cleanliness and Hoarding
      dimensions are associated with their symptom counterparts (i.e., contamination,
      checking, order, hoarding and neutralizing). OCSQ domains were highly associated
      with dysfunctional beliefs about obsessions. However, only the OCSQ scores, but
      not the dysfunctional beliefs, predicted OCD symptoms. These results support
      cognitive conceptualizations implicating self-concept in OCD development, and
      they suggest the need to further analyze the influence of self-worth in OCD
      development and maintenance.

PMID- 22386567
TI  - Serum concentrations of CRP, IL-6, TNF-alpha and cortisol in major depressive
      disorder with melancholic or atypical features.
AB  - The aim of the present study was to explore possible differences between serum C
      reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF
      alpha), and cortisol concentration in patients with major depressive disorder
      (MDD) with melancholic features, and MDD with atypical features. As secondary
      aim, we investigated possible associations with clinical features such as
      suicidal ideation, number of episodes, duration of depression and symptomatology
      severity. We included 55 MDD patients (32 with melancholic features and 23 with
      atypical features) and 18 healthy controls. When compared to healthy controls,
      MDD with melancholic or atypical features showed higher CRP and IL-6, but not TNF
      alpha. Cortisol concentration was higher in MDD with melancholic type, in
      comparison to the atypical type of MDD or controls. A positive correlation was
      found between the severity of depressive symptoms, concentrations of IL-6 and
      cortisol in the MDD group with melancholic features, while a negative correlation
      was observed between IL-6 and CRP in the MDD group with atypical feature. Also,
      in the MDD group with atypical features, there was a correlation between the
      severity of anxiety symptoms based on the Hamilton Rating Scale for Anxiety
      (HARS), concentration of CRP, and the duration of symptoms. In conclusion, we
      observed several differences in serum CRP, IL-6, and cortisol concentrations in
      MDD patients considering clinical features as well.

PMID- 22386568
TI  - Assessing the psychometric properties of the Internet Addiction Test (IAT) in US
      college students.
AB  - Internet addiction is a growing concern; however, both a clear understanding of
      the mechanisms driving problematic behaviors and a gold standard instrument for
      assessing symptoms are lacking. The purpose of this study was to perform a
      psychometric analysis of the most widely used screening instrument, the Young
      Internet Addiction Test (IAT), using a sample of US college students. 215 (70%
      response rate) undergraduate college students were recruited from two US
      universities to complete an online version of the IAT. Using exploratory factor
      analysis, two factors were extracted, "dependent use" and "excessive use" which
      together explained 91% of the total variance. Participants who scored into the
      problematic user category of the IAT scored items on the dependent use scale an
      average of 0.8 +/- 1.5 points higher and items on the excessive use scale an
      average of 1.4 +/- 1.5 points higher than participants who scored in the average
      user category. Results suggest that Internet addiction symptoms may cluster into
      two separate components, dependent and excessive use. Further, the IAT appears to
      be a valid instrument for assessing Internet addiction in US college students.

PMID- 22386569
TI  - Personality profile of adult ADHD: the alternative five factor model.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently
      diagnosed disorders in childhood affecting around 3% to 5% of adults worldwide.
      Most of the studies have been carried out using the Five Factor Model (FFM).
      Given the value and importance of describing adult ADHD in terms of general
      personality structure for a better conceptualization of this disorder, this study
      contributes adding new data on an Alternative Five Factor Model (AFFM) of
      personality. The aim of the present study is twofold: To assess the personality
      profile of adults with ADHD under the AFFM perspective, and to test the
      discriminant validity of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ)
      in differentiating ADHD subjects vs. normal range controls. A sample of 217
      adults (64% male) meeting ADHD diagnosis (DSM-IV) was paired by age and sex with
      434 normal-range controls. Logistic regression analysis showed that high scores
      on Neuroticism-Anxiety, Impulsivity and General Activity, and low on Work
      Activity were the most powerful predictors of being endorsed with an ADHD
      diagnosis. Results may suggest refinements in the personality assessment of ADHD
      as it seems that the ZKPQ provides more specific subscales for the description
      and conceptualization of this disorder.

PMID- 22386570
TI  - Markers of gluten sensitivity in acute mania: a longitudinal study.
AB  - Increased levels of antibodies to gliadin, which is derived from the wheat
      protein gluten, have been reported in schizophrenia and bipolar disorder in cross
      sectional studies. We examined longitudinally the levels of antibody reactivity
      to gliadin in acute mania. The sample included 60 individuals assessed during a
      hospital stay for acute mania, 39 at a 6-month follow-up, and a sample of 143 non
      psychiatric controls. Antibodies to gliadin were measured by enzyme immunoassay.
      The relationship of the antibodies to the clinical course of mania was analyzed
      by the use of regression models. Individuals with mania had significantly
      increased levels of IgG antibodies to gliadin, but not other markers of celiac
      disease, at baseline compared with controls in multivariate analyses. However,
      these levels were not significantly different from those of controls at the six
      month follow-up. Among the individuals with mania, elevated levels at follow-up
      were significantly associated with re-hospitalization in the 6-month follow-up
      period. The monitoring and control of gluten sensitivity may have significant
      effects on the management of individuals hospitalized with acute mania.

PMID- 22386571
TI  - Ecological study of isolation and suicide in Tuscany (Italy).
AB  - The purpose of the study was to investigate the association between suicide and
      demographic and socio-economic measures in Tuscany. Data on standardized rates of
      suicide from 1997 to 2005 in addition to census-derived variables, income and
      abstention were derived from the Mortality register, the 2001 Census, the Tax
      Agency and the Regional Electoral Office databases. Pearson's correlation and
      stepwise multiple regression analyses (unweighted and weighted by population)
      were used to analyze the association between suicide rates and demographic and
      socio-economic measures for the 34 health districts for both males and females.
      The correlation analyses showed that suicide was significantly associated with
      many variables in men, but only with old age in women. The multiple regression
      analyses showed that the best predictors in men were education, single person
      households and isolated houses (only education and single person households in
      the weighted model). For women, the best predictors were the proportion of
      elderly people and income (this was also true for the weighted model, but in the
      opposite order). An ecological correlation between suicide and measures of
      economic deprivation and social fragmentation was found in both men and women.
      Among the best predictors, isolated houses may act as a marker for remoteness and
      isolation on a small scale.

PMID- 22386572
TI  - Case-control association study of 14 variants of CREB1, CREBBP and CREM on
      diagnosis and treatment outcome in major depressive disorder and bipolar
      disorder.
AB  - Some evidence suggests an association between genetic variants within the cyclic
      adenosine monophosphate (cAMP) response element-binding protein (CREB), CREB
      binding protein (CREBBP) and cAMP response element-modulator (CREM) and several
      psychiatric disorders. The present study investigated whether some single
      nucleotide polymorphisms (SNPs) within these genes could be associated with major
      depressive disorder (MDD) and bipolar disorder (BD) and whether they could
      predict clinical outcomes in Korean in-patients treated with antidepressants and
      mood stabilizers, respectively. The sample comprised 145 patients with MDD, 132
      patients with BD and 170 psychiatrically healthy controls. Participants were
      genotyped for 14 SNPs within CREB1, CREBBP and CREM. Baseline and final clinical
      measures, including the Montgomery-Asberg Depression Rating Scale and Young Mania
      Rating Scale for patients with MDD and BD, respectively, were recorded. All p
      values were 2-tailed, and statistical significance was conservatively set at the
      0.006 level in order to reduce the likelihood of false positive results. We
      failed to observe any association of the 14 SNPs genotypes or alleles with
      clinical improvement, response and remission rates as well as final outcomes in
      any of such disorders. Our findings suggest that the 14 SNP under investigation
      in our study do not influence diagnosis and treatment response in patients with
      MDD and BD. However, taking into account the several limitations of our study,
      further research is needed to draw more definitive conclusions.

PMID- 22386573
TI  - High galectin-1 expression correlates with poor prognosis and is involved in
      epithelial ovarian cancer proliferation and invasion.
AB  - PURPOSE: Galectin-1 (Gal-1) is a 14-kDa laminin-binding galectin involved in
      several biological events including regulation of tumour proliferation and
      metastasis. In this study, we investigated the clinical significance of Gal-1
      expression and its functional role in cell proliferation and invasion in
      epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: We evaluated the expression
      of Gal-1 in 52 serous, 11 endometrioid, and 3 mucinous type EOC tumour samples
      from 66 patients by immunohistochemistry. In vitro experiments were performed to
      determine the function of Gal-1 in cell survival, proliferation, and invasion in
      EOC cells using siRNA and anginex, a Gal-1 inhibitor, as well as recombinant Gal
      1 protein. RESULTS: Patients with strong Gal-1 peritumoural staining had poorer
      progression-free survival (PFS) than patients with weak peritumoural staining
      (p=0.03). Inhibition of Gal-1 by siRNA or anginex resulted in the inhibition of
      cell growth and proliferation of HeyA8 and SKOV3ip1 cells. Moreover, the ability
      of cells to migrate was significantly reduced by treatment of cells with Gal-1
      siRNA but was increased by treatment of cells with recombinant Gal-1. When we
      evaluated the interaction between fibroblasts (T HESCs) and cancer cells (A2780
      CP20), we found that MMP-2 expression in cancer cells was affected by Gal-1
      secreted by fibroblast cells, which suggests that Gal-1 in human fibroblasts
      might affect the invasive abilities of tumour cells. CONCLUSION: Our results
      suggest that Gal-1 expression is a potential prognostic factor for PFS and that
      Gal-1 could be a novel treatment target in EOC patients.

PMID- 22386574
TI  - Evaluating the efficacy of statins and ACE-inhibitors in reducing
      gastrointestinal toxicity in patients receiving radiotherapy for pelvic
      malignancies.
AB  - INTRODUCTION: 3-Hydroxy-methylglutaryl coenzyme-a reductase inhibitors (statins)
      improve survival following pelvic irradiation for cancer. Large studies suggest
      that patients with hypertension may have reduced gastrointestinal (GI) toxicity.
      Animal data suggest that statins and ACE inhibitors (ACEi) may protect against
      normal tissue injury. Their efficacy in humans has not been reported.
      AIMS/METHODS: To evaluate the impact of statins and ACEi on normal tissue
      toxicity during radical pelvic radiotherapy. GI symptomatology was recorded
      prospectively before radiotherapy, weekly during treatment and 1 year later using
      the inflammatory bowel disease questionnaire-bowel (IBDQ-B) subset. Cumulative
      acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and
      duration of statin and/or ACEi usage were obtained from General Practitioners.
      RESULTS: Of 308 patients recruited, 237 had evaluable acute drug and toxicity
      data and 164 had data at 1year. Acutely, 38 patients (16%) were taking statins,
      39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking
      statin+ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3
      (non-ACEi users) and 7.0 (non-statin+ACEi users) compared to 4.8 points (statin
      users), 5.0 points (ACEi users) and 4.9 points (statin+ACEi users). Statin use
      (p=0.04) and combined statin+ACEi use (p=0.008) were associated with reduced
      acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users
      maintained higher IBDQ-B scores than non-users in all user subgroups. CONCLUSION:
      Use of statin or statin+ACEi medication during radical pelvic radiotherapy
      significantly reduces acute gastrointestinal symptoms scores and also appears to
      provide longer-term sustained protection.

PMID- 22386575
TI  - Relationship between CHA(2)DS(2)-VASc scores and ischemic stroke/cardiovascular
      events in Japanese patients with paroxysmal atrial fibrillation not receiving
      anticoagulant therapy.
AB  - BACKGROUND AND METHODS: The CHA(2)DS(2)-VASc score has been newly proposed for
      stratifying patients with nonvalvular atrial fibrillation (AF) according to the
      risk of ischemic stroke in the 2010 European Society of Cardiology guideline.
      However, there is little information about its usefulness for predicting long
      term prognosis of cardiovascular events in Japanese patients with paroxysmal AF.
      This study retrospectively included 332 paroxysmal AF patients (224 men, mean age
      65+/-13 years, mean follow-up period 53+/-35 months) without receiving
      anticoagulant therapy between June 1995 and August 2008 who were categorized into
      risk stratification on the basis of CHA(2)DS(2)-VASc score. RESULTS: The
      distribution of CHA(2)DS(2)-VASc scores was 0, 1, 2, 3, 4, 5, 6, and 7 points in
      76 (23%), 60 (18%), 69 (21%), 69 (21%), 28 (8%), 23 (7%), 6 (2%), and 1 (0.3%)
      patients, respectively. The annual rates of symptomatic ischemic stroke were 0%,
      0.60%, 0.95%, 1.96%, 5.45%, 9.06%, and 13.7% when the CHA(2)DS(2)-VASc score was
      0, 1, 2, 3, 4, 5, and >=6 points, respectively (p<0.001) and those of
      cardiovascular events including hospitalization for thromboembolism, heart
      failure and cardiovascular death were 0%, 1.43%, 1.50%, 2.52%, 10.14%, 12.85%,
      and 17.13% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5 and >=6 points,
      respectively (p<0.001). Higher CHA(2)DS(2)-VASc scores were associated with
      greater annual rates of ischemic stroke and cardiovascular events. In a
      multivariate logistic regression analysis adjusted for the potentially
      confounding variables, the CHA(2)DS(2)-VASc score was associated with symptomatic
      ischemic stroke (odds ratio 7.051, 95% confidence interval 3.76-13.22, p<0.001)
      and cardiovascular events (odds ratio 3.448, 95% confidence interval 2.33-5.11,
      p<0.001). CONCLUSION: In Japanese patients with paroxysmal AF, the CHA(2)DS(2)
      VASc score is a useful scheme for risk stratification of ischemic stroke and
      cardiovascular events.

PMID- 22386576
TI  - Iridoid and phenylethanoid glycosides in the New Zealand sun hebes (Veronica;
      Plantaginaceae).
AB  - The sun hebes are a small clade of New Zealand Veronica formerly classified as
      Heliohebe. The water-soluble compounds of Veronica pentasepala, Veronica raoulii
      and Veronica hulkeana were studied and 30 compounds including 15 iridoid
      glucosides, 12 phenylethanoid glycosides, the acetophenone glucoside pungenin,
      the mannitol ester hebitol II and mannitol were isolated. Of these, five were
      previously unknown in the literature: dihydroverminoside and 3,3',4,4'
      tetrahydroxy-alpha-truxillic acid 6-O-catalpyl diester, named heliosepaloside, as
      well as three phenylethanoid glycoside esters heliosides D, E and F, all
      derivatives of aragoside. The esters of cinnamic acid derivatives with iridoid
      and phenylethanoid glycosides and an unusually high concentration of verminoside
      were found to be the most distinctive chemotaxonomic characters of the sun hebes.
      The chemical profiles of the species were compared and used to assess the
      phylogenetic relationships in the group.

PMID- 22386577
TI  - Mass spectrometry imaging of glucosinolates in Arabidopsis flowers and siliques.
AB  - Glucosinolates are multi-functional plant secondary metabolites which play a
      vital role in plant defence and are, as dietary compounds, important to human
      health and livestock well-being. Knowledge of the tissue-specific regulation of
      their biosynthesis and accumulation is essential for plant breeding programs.
      Here, we report that in Arabidopsis thaliana, glucosinolates are accumulated
      differentially in specific cells of reproductive organs. Using matrix-assisted
      laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), distribution
      patterns of three selected compounds, 4-methylsulfinylbutyl (glucoraphanin),
      indol-3-ylmethyl (glucobrassicin), and 4-benzoyloxybutyl glucosinolates, were
      mapped in the tissues of whole flower buds, sepals and siliques. The results show
      that tissue localization patterns of aliphatic glucosinolate glucoraphanin and 4
      benzoyloxybutyl glucosinolate were similar, but indole glucosinolate
      glucobrassicin had different localisation, indicating a possible difference in
      function. The high resolution images obtained by a complementary approach, cryo
      SEM Energy Dispersive X-ray analysis (cryo-SEM-EDX), confirmed increased
      concentration of sulphur in areas with elevated amounts of glucosinolates, and
      allowed identifying the cell types implicated in accumulation of glucosinolates.
      High concentration of sulphur was found in S-cells adjacent to the phloem in
      pedicels and siliques, indicating the presence of glucosinolates. Moreover, both
      MALDI MSI and cryo-SEM-EDX analyses indicated accumulation of glucosinolates in
      cells on the outer surface of the sepals, suggesting that a layer of
      glucosinolate-accumulating epidermal cells protects the whole of the developing
      flower, in addition to the S-cells, which protect the phloem. This research
      demonstrates the high potential of MALDI MSI for understanding the cell-specific
      compartmentation of plant metabolites and its regulation.

PMID- 22386578
TI  - Active regulation of the epidermal calcium profile.
AB  - A distinct calcium profile is strongly implicated in regulating the multi-layered
      structure of the epidermis. However, the mechanisms that govern the regulation of
      this calcium profile are currently unclear. It clearly depends on the relatively
      impermeable barrier of the stratum corneum (passive regulation) but may also
      depend on calcium exchanges between keratinocytes and extracellular fluid (active
      regulation). Using a mathematical model that treats the viable sublayers of
      unwounded human and murine epidermis as porous media and assumes that their
      calcium profiles are passively regulated, we demonstrate that these profiles are
      also actively regulated. To obtain this result, we found that diffusion governs
      extracellular calcium motion in the viable epidermis and hence intracellular
      calcium is the main source of the epidermal calcium profile. Then, by comparison
      with experimental calcium profiles and combination with a hypothesised cell
      velocity distribution in the viable epidermis, we found that the net influx of
      calcium ions into keratinocytes from extracellular fluid may be constant and
      positive throughout the stratum basale and stratum spinosum, and that there is a
      net outflux of these ions in the stratum granulosum. Hence, the calcium exchange
      between keratinocytes and extracellular fluid differs distinctly between the
      stratum granulosum and the underlying sublayers, and these differences actively
      regulate the epidermal calcium profile. Our results also indicate that plasma
      membrane dysfunction may be an early event during keratinocyte disintegration in
      the stratum granulosum.

PMID- 22386579
TI  - Ontogeny of limb force distribution in squirrel monkeys (Saimiri boliviensis):
      insights into the mechanical bases of primate hind limb dominance.
AB  - The distribution of peak vertical forces between the forelimbs and the hind limbs
      is one of the key traits distinguishing primate quadrupedal locomotion from that
      of other mammals. Whereas most mammals generate greater peak vertical forelimb
      forces, primates generate greater peak vertical hind limb forces. At the ultimate
      level, hind limb dominance in limb force distribution is typically interpreted as
      an adaptation to facilitate fine-branch arboreality. However, the proximate
      biomechanical bases for primate limb force distribution remain controversial.
      Three models have been previously proposed. The Center of Mass (COM) Position
      model attributes primates' unique mode of limb loading to differences in the
      position of the whole-body COM relative to the hands and feet. The Active Weight
      Shift model asserts that primates actively redistribute body weight to their hind
      limbs by pitching the trunk up via the activation of hind limb retractor muscles.
      Finally, the Limb Compliance model argues that primates selectively mitigate
      forelimb forces by maintaining a compliant forelimb and a flat shoulder
      trajectory. Here, a detailed dataset of ontogenetic changes in morphology and
      locomotor mechanics in Bolivian squirrel monkeys (Saimiri boliviensis) was
      employed as a model system to evaluate each of these proposed models in turn.
      Over the first 10 months of life, squirrel monkeys transitioned from forelimb
      dominant infants to hind limb dominant juveniles, a change that was precipitated
      by decreases in peak vertical forelimb forces and increases in peak vertical hind
      limb forces. Results provided some support for all three of the models, although
      the COM Position and Active Weight Shift models were most strongly supported by
      the data. Overall, this study suggests that primates may use a variety of
      biomechanical strategies to achieve hind limb dominance in limb force
      distribution.

PMID- 22386580
TI  - Physical activity in midlife and telomere length measured in old age.
AB  - Physical activity has been associated with alterations in telomere length, a
      potential indicator of biological aging, but several inconsistencies exist. Our
      aim was to investigate the associations between physical activity in midlife and
      leukocyte telomere length (LTL) measured in old age in the Helsinki Businessmen
      Study, Finland. At entry, in 1974, 782 men (mean age 47) completed a
      questionnaire about their physical activity and this was collapsed into 3
      categories: low (n=148), moderate (n=398) and high physical activity (n=236, 7 of
      whom had a competitive activity level). After 29-year follow-up in 2003, mean LTL
      and the proportion of short (<5 kB) telomeres were measured from DNA samples of a
      random subcohort of survivors (n=204, mean age 76) using the Southern blot
      technique. Adjusted for age, body mass index (BMI), cholesterol and smoking in
      1974, the moderate physical activity group had longer mean LTL (8.27 kB, SE 0.05)
      than the low (8.10 kB, SE 0.07), or high (8.10 kB, SE 0.05) physical activity
      groups (P=0.03 between groups). Conversely, the proportion of short telomeres was
      lowest in the moderate physical activity group (11.35%, SE 0.25), and higher in
      the high (12.39%, SE 0.29), and the low physical activity (12.21%, SE 0.39)
      groups (P=0.02 between groups). We conclude that the results of this
      observational cohort study give support to the idea that both low and high
      physical activity is in the long-term associated with factors shortening LTL.

PMID- 22386581
TI  - Diet quality and cognition among older adults from the NuAge study.
AB  - BACKGROUND AND OBJECTIVES: A healthy diet may prevent cognitive decline either
      directly, or by decreasing risk of nutrition-related chronic diseases associated
      with cognitive decline. This study examined the relationships between diet
      quality (DQ) and cognition for over 3 years among 1488 older adults (52.6%
      female) from the NuAge study, aged 67 to 84 years at recruitment. METHODS:
      Cognition was assessed at four annual visits using the modified mini-mental
      status examination (3MS); rate of cognitive decline was computed for each
      participant over the 3 years of follow-up using mixed model analyses and the
      individual-specific number of months between 3MS assessments. Dietary data were
      collected at recruitment using a validated 78-item, semi-quantitative food
      frequency questionnaire (FFQ). DQ was characterized as the Canadian Healthy
      Eating Index (C-HEI), a 9-component global DQ index (maximum score=100) computed
      from the FFQ output. Other variables were collected by questionnaire or direct
      measurement. Multivariate analyses were carried out to assess the association of
      DQ controlled for confounders on cognition. RESULTS: Total C-HEI was better in
      females (78.7+/-9.1 vs 75.7+/-9.4, p<.0001) as were C-HEI component subscores.
      Males, the less educated, smokers, those with poor social engagement, symptoms of
      depression, a higher waist:hip ratio and who reported financial insecurity had a
      poor quality diet that could contribute to chronic diseases associated with
      cognition. Along with functional autonomy, most of these variables emerged as
      covariates of baseline 3MS and predictors of cognitive decline. While certain C
      HEI subscores and total C-HEI were positive univariate correlates of 3MS at
      recruitment, total DQ was not associated with cognition in multivariate analyses,
      either at baseline or over 3 years of follow-up. CONCLUSIONS: DQ was not
      independently associated with cognition. However, the study demonstrates
      relationships between diet quality and risk factors for chronic diseases
      associated with cognition. Consequently, older adults might benefit from a
      healthy diet to decrease risk of nutrition-related chronic diseases established
      as risk factors for cognitive decline. Further work in diverse older populations,
      use of dietary data collected earlier in life, finer cognitive measures and
      longer follow-up are necessary to better elucidate relationships between diet
      quality, chronic diseases and cognition.

PMID- 22386582
TI  - Hemodynamic monitoring in the critically ill: spanning the range of kidney
      function.
AB  - Critically ill patients often have deranged hemodynamics. Physical examination,
      central venous pressure, and pulmonary artery occlusion pressure ("wedge") have
      been shown to be unreliable at assessing volume status, volume responsiveness,
      and adequacy of cardiac output in critically ill patients. Thus, invasive and
      noninvasive cardiac output monitoring is a core feature of evaluating and
      managing a hemodynamically unstable patient. In this review, we discuss the
      various techniques and options of cardiac output assessment available to
      clinicians for hemodynamic monitoring in the intensive care unit. Issues related
      to patients with kidney disease, such as timing and location of arterial and
      central venous catheters and the approach to hemodynamics in patients treated by
      long-term dialysis also are discussed.

PMID- 22386583
TI  - How can nurses facilitate patient's transitions from intensive care?: a grounded
      theory of nursing.
AB  - OBJECTIVES: Intensive care patients often experience feelings of powerlessness
      and vulnerability when being transferred from an intensive care unit to a general
      ward. The aim of this study was to develop a grounded theory of nurses care for
      patients in the ICU transitional care process. METHODS: Group interviews,
      individual interviews and participant observations were conducted with nurses in
      two hospitals in Sweden and were analysed using grounded theory. RESULT: The
      substantive theory shows the process of nursing care activities - from the
      contexts of the ICU and the general ward. The main concern was to achieve a
      coordinated, strengthening, person-centered standard of care to facilitate
      patient transitions. The core category "being perceptive and adjustable" was a
      strategy to individualise, that was related to the other categories; "preparing
      for a change" and "promoting the recovery". However, the nurses were forced to
      "balance between patient needs and the caregivers' resources" and consequently
      were compromising their care. CONCLUSIONS: To facilitate an ICU-patient's
      transition, individual care planning is needed. It is also essential that the
      patients are adequately prepared for the change to facilitate the transitional
      care. Knowledge about transitional needs, empowerment and patient-education seems
      to be important issues for facilitating transitions.

PMID- 22386584
TI  - Prevalence, management and clinical challenges associated with acute faecal
      incontinence in the ICU and critical care settings: the FIRST cross-sectional
      descriptive survey.
AB  - OBJECTIVE: To evaluate the prevalence, awareness and management of acute faecal
      incontinence with diarrhoea (AFId) in the Intensive Care Unit. DESIGN: Cross
      sectional descriptive survey design of intensive care units across Germany,
      Italy, Spain and the United Kingdom. RESULTS: 962 questionnaires were completed
      by nurses (60%), physicians (29%) and pharmacists or purchasing personnel (11%).
      The estimated prevalence of AFId ranged from 9 to 37% of patients on the day of
      the survey. The majority of respondents reported a low-moderate awareness of the
      clinical challenges associated with AFId. Patients with AFId commonly had
      compromised skin integrity, which included perineal dermatitis, moisture lesions
      or sacral pressure ulcers. Reducing the risk of cross-infection and protecting
      skin integrity were rated as the most important clinical challenges. 49% had no
      hospital protocol or guideline for AFId management. There was also a low
      awareness of nursing time spent managing AFId; 60% of respondents estimated that
      10-20 minutes are required for managing an AFId episode by 2-3 healthcare staff.
      CONCLUSIONS: AFId in the critical care setting may be an underestimated problem
      which is associated with a high use of nursing time.

PMID- 22386585
TI  - Congenital supravalvular mitral stenosis in 14 cats.
AB  - OBJECTIVES: To describe the clinical features of congenital supravalvular mitral
      stenosis (SVMS) in cats. BACKGROUND: Supravalvular mitral stenosis is an uncommon
      congenital cardiac defect that has not been previously reported in a series of
      cats. ANIMALS: 14 cats with SVMS. METHODS: Medical records, relevant diagnostic
      studies and preserved pathology specimens were reviewed. RESULTS: Cats were
      presented over a wide age range (5 months-10 years; median 3 years); males (n =
      9) and the Siamese breed were over-represented. Presenting complaints included
      respiratory distress (n = 6), hindlimb paralysis due to aortic thromboembolism (n
      = 5) and asymptomatic heart murmur (n = 3). Echocardiographic examination often
      identified pulmonary hypertension (PHT) (n = 7) and concurrent cardiac
      abnormalities (n = 7), especially partial atrioventricular septal defect (PAVSD)
      (n = 4). Status 12 months following diagnosis was known for 9 cats; 8 of these
      had died or were euthanized. CONCLUSIONS: Cats with SVMS are usually presented as
      young adults for respiratory signs attributable to congestive heart failure,
      aortic thromboembolism or incidental murmur identification. Congestive heart
      failure, PHT and concurrent congenital cardiac abnormalities (specifically PAVSD)
      are common. Long-term prognosis for symptomatic cats is poor.

PMID- 22386586
TI  - Interactions between TGFbeta1 and cyclic strain in modulation of myofibroblastic
      differentiation of canine mitral valve interstitial cells in 3D culture.
AB  - OBJECTIVES: The mechanisms of myxomatous valve degeneration (MVD) are poorly
      understood. Transforming growth factor-beta1 (TGFbeta1) induces myofibroblastic
      activation in mitral valve interstitial cells (MVIC) in static 2D culture, but
      the roles of more physiological 3D matrix and cyclic mechanical strain are
      unclear. In this paper, we test the hypothesis that cyclic strain and TGFbeta1
      interact to modify MVIC phenotype in 3D culture. ANIMALS, MATERIALS AND METHODS:
      MVIC were isolated from dogs with and without MVD and cultured for 7 days in type
      1 collagen hydrogels with and without 5 ng/ml TGFbeta1. MVIC with MVD were
      subjected to 15% cyclic equibiaxial strain with static cultures serving as
      controls. Myofibroblastic phenotype was assessed via 3D matrix compaction, cell
      morphology, and expression of myofibroblastic (TGFbeta3, alpha-smooth muscle
      actin - alphaSMA) and fibroblastic (vimentin) markers. RESULTS: Exogenous
      TGFbeta1 increased matrix compaction by canine MVIC with and without MVD, which
      correlated with increased cell spreading and elongation. TGFbeta1 increased
      alphaSMA and TGFbeta3 gene expression, but not vimentin expression, in 15%
      cyclically stretched MVIC. Conversely, 15% cyclic strain significantly increased
      vimentin protein and gene expression, but not alphaSMA or TGFbeta3. 15% cyclic
      strain however was unable to counteract the effects of TGFbeta1 stimulation on
      MVIC. CONCLUSIONS: These results suggest that TGFbeta1 induces myofibroblastic
      differentiation (MVD phenotype) of canine MVIC in 3D culture, while 15% cyclic
      strain promotes a more fibroblastic phenotype. Mechanical and biochemical
      interactions likely regulate MVIC phenotype with dose dependence. 3D culture
      systems can systematically investigate these phenomena and identify their
      underlying molecular mechanisms.

PMID- 22386587
TI  - Pathology of myxomatous mitral valve disease in the dog.
AB  - Mitral valve competence requires complex interplay between structures that
      comprise the mitral apparatus - the mitral annulus, mitral valve leaflets,
      chordae tendineae, papillary muscles, and left atrial and left ventricular
      myocardium. Myxomatous mitral valve degeneration is prevalent in the canine, and
      most adult dogs develop some degree of mitral valve disease as they age,
      highlighting the apparent vulnerability of canine heart valves to injury.
      Myxomatous valvular remodeling is associated with characteristic histopathologic
      features. Changes include expansion of extracellular matrix with
      glycosaminoglycans and proteoglycans; valvular interstitial cell alteration; and
      attenuation or loss of the collagen-laden fibrosa layer. These lead to
      malformation of the mitral apparatus, biomechanical dysfunction, and mitral
      incompetence. Mitral regurgitation is the most common manifestation of myxomatous
      valve disease and in advanced stages, associated volume overload promotes
      progressive valvular regurgitation, left atrial and left ventricular remodeling,
      atrial tears, chordal rupture, and congestive heart failure. Future studies are
      necessary to identify clinical-pathologic correlates that track disease severity
      and progression, detect valve dysfunction, and facilitate risk stratification. It
      remains unresolved whether, or to what extent, the pathobiology of myxomatous
      mitral valve degeneration is the same between breeds of dogs, between canines and
      humans, and how these features are related to aging and genetics.

PMID- 22386588
TI  - Historical review, epidemiology and natural history of degenerative mitral valve
      disease.
AB  - Chronic mitral valve disease due to myxomatous degeneration (MMVD) is the most
      common cardiovascular disease in dogs and has been known to cause congestive
      heart failure for more than 100 years. This article presents an historical
      perspective of the disease and reviews the most updated data on epidemiology and
      natural history of MMVD in dogs.

PMID- 22386590
TI  - Astasia-abasia and psychogenic tremor post-temporal lobectomy.
AB  - Temporal lobectomy can be complicated by somatoform disorders, psychiatric
      illnesses and non-epileptic psychogenic seizures. We report a woman who developed
      astasia-abasia and psychogenic tremor following temporal lobectomy for refractory
      epilepsy. To our knowledge, this type of conversion reaction following temporal
      lobectomy has not been previously reported.

PMID- 22386589
TI  - Structure and functional characterization of the RNA-binding element of the NLRX1
      innate immune modulator.
AB  - Mitochondrial NLRX1 is a member of the family of nucleotide-binding domain and
      leucine-rich-repeat-containing proteins (NLRs) that mediate host innate immunity
      as intracellular surveillance sensors against common molecular patterns of
      invading pathogens. NLRX1 functions in antiviral immunity, but the molecular
      mechanism of its ligand-induced activation is largely unknown. The crystal
      structure of the C-terminal fragment (residues 629-975) of human NLRX1 (cNLRX1)
      at 2.65 A resolution reveals that cNLRX1 consists of an N-terminal helical
      (LRRNT) domain, central leucine-rich repeat modules (LRRM), and a C-terminal
      three-helix bundle (LRRCT). cNLRX1 assembles into a compact hexameric
      architecture that is stabilized by intersubunit and interdomain interactions of
      LRRNT and LRRCT in the trimer and dimer components of the hexamer, respectively.
      Furthermore, we find that cNLRX1 interacts directly with RNA and supports a role
      for NLRX1 in recognition of intracellular viral RNA in antiviral immunity.

PMID- 22386591
TI  - New observations in primary and secondary reading epilepsy: excellent response to
      levetiracetam and early spontaneous remission.
AB  - The response of reading epilepsy to new antiepileptic drugs is not known. Due to
      the rarity of this condition little is known about its natural history. We
      evaluated and treated three patients with primary and secondary reading epilepsy.
      Seizures in all patients were characterized by twitching of the jaw or lips with
      secondarily generalized tonic-clonic seizures if reading continued. One patient
      with primary reading epilepsy became seizure-free with divalproex monotherapy and
      another with levetiracetam monotherapy after failure of lamotrigine. One other
      patient with secondary reading epilepsy became seizure-free with levetiracetam
      add-on therapy. The divalproex-treated patient stopped therapy less than 3 years
      after seizure onset and remained seizure-free with 6 years of follow-up. We
      propose levetiracetam as a first-line treatment for primary and secondary reading
      epilepsy. Spontaneous medication-free remission of primary reading epilepsy may
      occur within 3 years of seizure onset, much earlier than previously reported.

PMID- 22386592
TI  - Estimation of running capacity can likely be removed from questionnaires
      estimating walking impairment in patients with claudication.
AB  - OBJECTIVE: The Estimating Ambulation Capacity by History-Questionnaire (EACH-Q)
      and the Walking Impairment Questionnaire (WIQ) are used to estimate maximal
      walking distance (MWD). The EACH-Q and WIQ included 4 and 14 items respectively,
      among which one item dealing with running capacity. We hypothesised that this
      item was of little interest in patients with claudication. DESIGN: The WIQ and
      EACH-Q were self-completed and corrected before a constant load (3.2 km h(-1);
      10% slope) treadmill tests, maximised to 15 min. PATIENTS: 371 patients (298
      males/73 females, 62.9 +/- 11.2 years). METHODS: The number of errors (duplicate,
      absent or paradoxical answers to one item) and correlation of questionnaire
      scores with MWD on treadmill were calculated, before and after skipping the
      answer to the running item. RESULTS: The proportion of questionnaires with errors
      was 27% with the EACH-Q and 48% with the WIQ. Two-hundred and twenty-one (59.6%)
      and 245 (66%) out of 371 patients reported to be unable to run, for the EACH-Q
      and WIQ, respectively. The rate of errors was reduced by 15% for the EACH-Q (p <
      0.05) when skipping the running item for scoring. The correlation coefficients
      between the MWD and the questionnaire scores were 0.449 and 0.485 for the EACH-Q
      and were 0.571 and 0.572 for the WIQ, before and after skipping the running item,
      respectively. CONCLUSION: Most of our patients reported to be unable to run and
      skipping the running item reduce the rate of errors in self-completing the
      questionnaires without impairing the correlation of questionnaire scores with
      treadmill results. It is likely that the running item could be removed from the
      WIQ and EACH-Q questionnaires.

PMID- 22386593
TI  - PGD for inherited cardiac diseases.
AB  - Preimplantation genetic diagnosis (PGD) has been applied for more than 200
      different inherited conditions, with expanding application to common disorders
      with genetic predisposition. One of the recent indications for PGD has been
      inherited cardiac disease, for which no preclinical diagnosis and preventive
      management may exist and which may lead to premature or sudden death. This paper
      presents the first, as far as is known, cumulative experience of PGD for
      inherited cardiac diseases, including familial hypertrophic and dilated
      cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A
      total of 18 PGD cycles were performed, resulting in transfer in 15 of them, which
      yielded nine unaffected pregnancies and the births of seven disease- or disease
      predisposition-free children. The data open the prospect of PGD for inherited
      cardiac diseases, allowing couples carrying cardiac disease predisposing genes to
      reproduce without much fear of having offspring with these genes, which are at
      risk for premature or sudden death. Preimplantation genetic diagnosis (PGD) is
      currently an established clinical procedure in assisted reproduction and genetic
      practices. Its application has been expanding beyond traditional indications of
      prenatal diagnosis and currently includes common disorders with genetic
      predisposition, such as inherited forms of cancer. This applies also to the
      diseases with no current prospect of treatment, which may manifest despite
      presymptomatic diagnosis and follow up, when PGD may provide the only relief for
      the at-risk couples to reproduce. One of the recent indications for PGD has been
      inherited cardiac disease, for which no preclinical diagnosis and preventive
      management may exist and which may lead to premature or sudden death. We present
      here our first cumulative experience of PGD for inherited cardiac diseases,
      including familial hypertrophic and dilated cardiomyopathy,
      cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD
      cycles for these disorders was performed, resulting in transfer in 15 of them,
      which yielded nine unaffected pregnancies and birth of seven disease- or disease
      predisposition-free children. The data open the prospect of PGD for inherited
      cardiac diseases, allowing couples carrying cardiac disease predisposing genes to
      reproduce without much fear of having offspring with these genes at risk for
      premature or sudden death.

PMID- 22386594
TI  - Comparative incidence of ovarian hyperstimulation syndrome following ovarian
      stimulation with corifollitropin alfa or recombinant FSH.
AB  - Corifollitropin alfa is a novel recombinant gonadotrophin with sustained follicle
      stimulating activity. A single injection can replace seven daily injections of
      recombinant follicle-stimulating hormone (rFSH) during the first week of ovarian
      stimulation. All cases of ovarian hyperstimulation syndrome (OHSS) with
      corifollitropin alfa intervention in a gonadotrophin-releasing hormone antagonist
      protocol have been assessed in three large trials: Engage, Ensure and Trust.
      Overall, 1705 patients received corifollitropin alfa and 5.6% experienced mild,
      moderate or severe OHSS. In the randomized controlled trials, Engage and Ensure,
      the pooled incidence of OHSS with corifollitropin alfa was 6.9% (71/1023
      patients) compared with 6.0% (53/880 patients) in the rFSH group. Adjusted for
      trial, the odds ratio for OHSS was 1.18 (95% CI 0.81-1.71) indicating that the
      risk of OHSS for corifollitropin alfa was similar to that for rFSH. The incidence
      of mild, moderate and severe OHSS was 3.0%, 2.2% and 1.8%, respectively, with
      corifollitropin alfa, with 1.9% requiring hospitalization, and 3.5%, 1.3% and
      1.3%, respectively, in the rFSH arms, with 0.9% requiring hospitalization.
      Despite a higher ovarian response with corifollitropin alfa compared with rFSH
      for the first 7days of ovarian stimulation, the incidence of OHSS was similar.
      Corifollitropin alfa is a new agent used in ovarian stimulation treatment for IVF
      fertilization. One injection of corifollitropin alfa can replace seven injections
      of recombinant FSH (rFSH). In three studies of corifollitropin alfa treatment, we
      assessed all cases of ovarian hyperstimulation syndrome (OHSS), a potentially
      serious complication of ovarian stimulation treatment. Overall, 5.6% of the
      patients (95/1701) experienced OHSS. Two of the trials compared corifollitropin
      alfa versus rFSH. Because OHSS is relatively rare, we pooled the results of these
      trials to give a more reliable estimate of the incidence of OHSS. In the pooled
      analysis, 6.9% (71/1023) of patients receiving corifollitropin alfa had signs or
      symptoms of OHSS, compared with 6.0% in the rFSH group (53/880). The risk of OHSS
      with corifollitropin alfa treatment was similar to the risk of OHSS in patients
      who received rFSH: the incidence of mild, moderate and severe OHSS was 3.0%, 2.2%
      and 1.8%, respectively, in patients in the corifollitropin alfa treatment groups,
      with 1.9% requiring hospitalisation, and 3.5%, 1.3% and 1.3%, respectively, in
      patients in the rFSH treatment groups, with 0.9% requiring hospitalization.
      Although the ovaries respond more to corifollitropin alfa than to rFSH for the
      first 7days of ovarian stimulation, neither treatment regimen was significantly
      more likely to cause OHSS.

PMID- 22386595
TI  - Peritoneal fluid modifies the response of human spermatozoa to follicular fluid.
AB  - The aim of this study was to elucidate the mechanism involved in the acrosome
      reaction (AR) induced by follicular fluid (FF) in spermatozoa previously exposed
      to peritoneal fluid (PF). The influence of progesterone was also investigated.
      Semen samples were from 18 normozoospermic donors. PF samples were from 13 women
      with unexplained infertility and from a woman treated with synthetic progestagen.
      FF samples were collected from six women undergoing IVF/embryo transfer and
      pooled. Motile spermatozoa were capacitated overnight and a kinetic and
      inhibition study on the FF-induced AR was performed. Spermatozoa pretreated with
      PF were challenged with either FF or progesterone. The ability of progesterone-
      and progestagen-supplemented PF to induce AR was analysed. Enzyme-digested PF was
      also tested. Pre-incubation with PF for 60 min completely prevented the FF
      induced AR; spermatozoa treated with PF were unable to respond to FF or
      progesterone and this effect was not reversible. Progesterone- and progestagen
      supplemented PF stimulated the AR relative to controls. Enzyme-digested PF did
      not have an inhibitory capacity. These data strongly suggest that there are one
      or more inhibitory proteins in PF that interact with spermatozoa so as to prevent
      access of progesterone to its receptor and thus inhibit the occurrence of the AR.
      The oviduct, or Fallopian tube, provides a place for spermatozoa and egg
      transport and storage, fertilization and early embryo development. If ovulation
      has not occurred, spermatozoa may reside in the oviduct for several hours or even
      a few days, awaiting oocyte arrival. It is assumed that fluids present in the
      female genital tract may have a role in synchronizing the timing required to
      guarantee the success of fertilization. We previously observed that the
      peritoneal fluid that bathes the peritoneal cavity is a suitable medium for sperm
      survival and we also reported that this fluid could stabilize spermatozoa. In
      this study we show further evidence that the exposure to peritoneal fluid
      modifies the response of spermatozoa to oocyte signals.

PMID- 22386596
TI  - RAGE binds C1q and enhances C1q-mediated phagocytosis.
AB  - RAGE, the multiligand receptor of the immunoglobulin superfamily of cell surface
      molecules, is implicated in innate and adaptive immunity. Complement component
      C1q serves roles in complement activation and antibody-independent opsonization.
      Using soluble forms of RAGE (sRAGE) and RAGE-expressing cells, we determined that
      RAGE is a native C1q globular domain receptor. Direct C1q-sRAGE interaction was
      demonstrated with surface plasmon resonance (SPR), with minimum K(d) 5.6 MUM, and
      stronger binding affinity seen in ELISA-like experiments involving multivalent
      binding. Pull-down experiments suggested formation of a receptor complex of RAGE
      and Mac-1 to further enhance affinity for C1q. C1q induced U937 cell adhesion and
      phagocytosis was inhibited by antibodies to RAGE or Mac-1. These data link C1q
      and RAGE to the recruitment of leukocytes and phagocytosis of C1q-coated
      material.

PMID- 22386597
TI  - Real-time human-robot interaction underlying neurorobotic trust and intent
      recognition.
AB  - In the past three decades, the interest in trust has grown significantly due to
      its important role in our modern society. Everyday social experience involves
      "confidence" among people, which can be interpreted at the neurological level of
      a human brain. Recent studies suggest that oxytocin is a centrally-acting
      neurotransmitter important in the development and alteration of trust. Its
      administration in humans seems to increase trust and reduce fear, in part by
      directly inhibiting the amygdala. However, the cerebral microcircuitry underlying
      this mechanism is still unknown. We propose the first biologically realistic
      model for trust, simulating spiking neurons in the cortex in a real-time human
      robot interaction simulation. At the physiological level, oxytocin cells were
      modeled with triple apical dendrites characteristic of their structure in the
      paraventricular nucleus of the hypothalamus. As trust was established in the
      simulation, this architecture had a direct inhibitory effect on the amygdala
      tonic firing, which resulted in a willingness to exchange an object from the
      trustor (virtual neurorobot) to the trustee (human actor). Our software and
      hardware enhancements allowed the simulation of almost 100,000 neurons in real
      time and the incorporation of a sophisticated Gabor mechanism as a visual filter.
      Our brain was functional and our robotic system was robust in that it trusted or
      distrusted a human actor based on movement imitation.

PMID- 22386598
TI  - Network properties of a computational model of the dorsal raphe nucleus.
AB  - Serotonin (5-HT) plays an important role in regulating mood, cognition and
      behaviour. The midbrain dorsal raphe nucleus (DRN) is one of the primary sources
      of 5-HT. Recent studies show that DRN neuronal activities can encode rewarding
      (e.g., appetitive) and unrewarding (e.g., aversive) behaviours. Experiments have
      also shown that DRN neurons can exhibit heterogeneous spiking behaviours. In this
      work, we build and study a basic spiking neuronal network model of the DRN
      constrained by neuronal properties observed in experiments. We use an efficient
      adaptive quadratic integrate-and-fire neuronal model to capture slow
      afterhyperpolarization current, occasional bursting behaviours in 5-HT neurons,
      and fast spiking activities in the non-5-HT inhibitory neurons. Provided that our
      noisy and heterogeneous spiking neuronal network model adopts a feedforward
      inhibitory network architecture, it is able to replicate the main features of DRN
      neuronal activities recorded in monkeys performing a reward-based memory-guided
      saccade task. The model exhibits theta band oscillation, especially among the non
      5-HT inhibitory neurons during the rewarding outcome of a simulated trial, thus
      forming a model prediction. By varying the inhibitory synaptic strengths and the
      afferent inputs, we find that the network model can oscillate over a range of
      relatively low frequencies, allow co-existence of multiple stable frequencies,
      and spike synchrony can spread from within a local neural subgroup to global. Our
      model suggests plausible network architecture, provides interesting model
      predictions that can be experimentally tested, and offers a sufficiently
      realistic multi-scale model for 5-HT neuromodulation simulations.

PMID- 22386599
TI  - Autonomous Growing Neural Gas for applications with time constraint: optimal
      parameter estimation.
AB  - This paper aims to address the ability of self-organizing neural network models
      to manage real-time applications. Specifically, we introduce fAGNG (fast
      Autonomous Growing Neural Gas), a modified learning algorithm for the incremental
      model Growing Neural Gas (GNG) network. The Growing Neural Gas network with its
      attributes of growth, flexibility, rapid adaptation, and excellent quality of
      representation of the input space makes it a suitable model for real time
      applications. However, under time constraints GNG fails to produce the optimal
      topological map for any input data set. In contrast to existing algorithms, the
      proposed fAGNG algorithm introduces multiple neurons per iteration. The number of
      neurons inserted and input data generated is controlled autonomous and
      dynamically based on a priory or online learnt model. A detailed study of the
      topological preservation and quality of representation depending on the neural
      network parameter selection has been developed to find the best alternatives to
      represent different linear and non-linear input spaces under time restrictions or
      specific quality of representation requirements.

PMID- 22386600
TI  - A meta-cognitive learning algorithm for a Fully Complex-valued Relaxation
      Network.
AB  - This paper presents a meta-cognitive learning algorithm for a single hidden layer
      complex-valued neural network called "Meta-cognitive Fully Complex-valued
      Relaxation Network (McFCRN)". McFCRN has two components: a cognitive component
      and a meta-cognitive component. A Fully Complex-valued Relaxation Network (FCRN)
      with a fully complex-valued Gaussian like activation function (sech) in the
      hidden layer and an exponential activation function in the output layer forms the
      cognitive component. The meta-cognitive component contains a self-regulatory
      learning mechanism which controls the learning ability of FCRN by deciding what
      to-learn, when-to-learn and how-to-learn from a sequence of training data. The
      input parameters of cognitive components are chosen randomly and the output
      parameters are estimated by minimizing a logarithmic error function. The problem
      of explicit minimization of magnitude and phase errors in the logarithmic error
      function is converted to system of linear equations and output parameters of FCRN
      are computed analytically. McFCRN starts with zero hidden neuron and builds the
      number of neurons required to approximate the target function. The meta-cognitive
      component selects the best learning strategy for FCRN to acquire the knowledge
      from training data and also adapts the learning strategies to implement best
      human learning components. Performance studies on a function approximation and
      real-valued classification problems show that proposed McFCRN performs better
      than the existing results reported in the literature.

PMID- 22386601
TI  - The effect of molecular weight, compositions and lectin type on the properties of
      hyperbranched glycopolymers as non-viral gene delivery systems.
AB  - The architectures of gene delivery vectors, in addition to their molecular
      weights and compositions, can play a critical role in DNA condensation and hence
      on their gene expression. In general, branched polymers are superior gene
      delivery vectors as compared to their linear analogs. This study reports the
      efficacy of cationic hyperbranched glycopolymers for DNA condensation and gene
      expression. Hyperbranched glycopolymers of varying molecular weights and
      compositions are synthesized via reversible addition fragmentation chain transfer
      (RAFT) process and are further explored for their gene expression in vitro.
      Galactose-based hyperbranched polymers are compared to glucose-derived
      hyperbranched polymers for their cellular uptake, toxicity and gene expression.
      It is found that molecular weight of hyperbranched polymers, and carbohydrate
      content of copolymers are critical factors in determining the gene expression as
      well as in imparting the specificity to these novel gene delivery vectors. The
      galactose-based hyperbranched glycopolymer of ~30 kDa or lower show improved gene
      expression at varying polymer/plasmid ratios. The incubation of hyperbranched
      polyplexes in the presence of serum protein show the presence of stable particles
      and gene expression of these hyperbranched polyplexes is unaffected in the
      presence of serum proteins. Furthermore, the cellular uptake and gene expression
      are studied in two different cell lines in the presence of lectins. It is found
      that polyplexes-lectin conjugates show enhanced cellular uptake in vitro, however
      their gene expression is cell line and lectin type dependent.

PMID- 22386602
TI  - Psychological effects of Tai Chi Chuan.
AB  - This article reviews the scientific studies which have been carried out at the
      international level on the psychological benefits that Tai Chi Chuan (TCC) brings
      to those who practice it. It analyzes the framework in which the research was
      performed, the real benefits that this activity achieves and their causes. The
      present article brings a new analytical perspective to the reviews carried out to
      date in regard to classifying and analyzing the psychological variables involved
      in the practice of TCC and offers a homogeneous framework within which to develop
      research in this field based on the model proposed by Spirduso et al. (2005).

PMID- 22386603
TI  - ICRP Publication 116. Conversion coefficients for radiological protection
      quantities for external radiation exposures.

PMID- 22386604
TI  - Effect of immediate postoperative physical therapy on length of stay for total
      joint arthroplasty patients.
AB  - The isolated effect of physical therapy (PT) on total joint arthroplasty hospital
      length of stay (LOS) has not been studied. A prospective cohort study was
      conducted on 136 primary total joint arthroplasties (58 hips, 78 knees). The LOS
      was determined by the operative start time until the time of discharge. On
      postoperative day (POD) 0, 60 joints remained in bed, 51 moved to a chair, and 25
      received PT (22 ambulated, 3 moved to a chair). Length of stay differed for
      patients receiving PT on POD 0 (2.8 +/- 0.8 days) compared with POD 1 (3.7 +/-
      1.8 days) (P = .02). There was no difference in PT treatment based on
      nausea/vomiting, pain levels, or discharge location. Isolated PT intervention on
      POD 0 shortened hospital LOS, regardless of the intervention performed.

PMID- 22386605
TI  - Revision total knee arthroplasty: infection should be ruled out in all cases.
AB  - We hypothesized that some aseptic revision total knee arthroplasty failures are
      indeed caused by occult infection. This prospective study recruited 65 patients
      undergoing revision total knee arthroplasty. The mean follow-up period was 19
      months. Collected synovial fluid was analyzed by Ibis T5000 biosensor (Abbott
      Molecular Inc, Ill; a multiplex polymerase chain reaction technology). Cases were
      considered as infected or aseptic based on the surgeon's judgment and Ibis
      findings. Based on Ibis biosensor, 17 aseptic cases were indeed infected that had
      been missed. Of these 17 cases, 2 developed infection after the index revision. A
      considerable number of so-called aseptic failures seem to be occult infections
      that were not adequately investigated and/or miscategorized as aseptic failure.
      We recommend that all patients undergoing revision arthroplasty be investigated
      for periprosthetic joint infection.

PMID- 22386606
TI  - Comparison of total hip and knee arthroplasty cohorts and short-term outcomes
      from a single-center joint registry.
AB  - The purpose of this study was to compare short-term clinical outcomes between
      total hip arthroplasty (THA) and total knee arthroplasty (TKA) patient cohorts,
      adjusting for confounding variables including age, sex, body mass index,
      operative time, length of stay, and preoperative Western Ontario and McMaster
      Universities and 12-Item Short-Form Health Survey. A total of 349 patients who
      met inclusion and exclusion criteria created 2 cohorts: THA, 194, and TKA, 155,
      for statistical analysis via multiple regression and analysis of covariance
      measures. Outcome measures included Western Ontario and McMaster Universities and
      12-Item Short-Form Health Survey data, collected prospectively at baseline and 2
      years of follow-up. The current study showed that baseline characteristics of TKA
      patients have more factors with negative effect on postoperative outcome than
      THA. However, despite controlling for the possible confounding effect of these
      variables, THA patients experienced a significantly better functional outcome
      than TKA patients.

PMID- 22386607
TI  - Temporal-spatial gait adaptations during stair ascent and descent in patients
      with knee osteoarthritis.
AB  - Knee osteoarthritis (OA) accounts for more functional disability of the lower
      extremity than any other disease. We recruited 18 patients with knee OA and 18
      healthy age-, height-, mass-, and gender-matched control subjects to investigate
      the effects knee OA has on select spatial and temporal gait variables during a
      stair climbing task. No group-by-direction interaction was observed; however,
      significant effects did occur for group and direction. Specifically, patients
      with knee OA demonstrated less time in single support, greater time in double
      support, decreased step length, greater step width, less stride length, decreased
      total gait velocity, greater total time in support, and less total time in swing,
      compared with controls. Early-stage knee OA directly influences specific temporal
      and spatial gait characteristics during stair climbing.

PMID- 22386608
TI  - Ipsilateral diaphyseal femur fracture after resection arthroplasty.
AB  - Resection arthroplasty of the hip is most commonly used for recalcitrant
      infections in the setting of prior hemiarthroplasty and total hip arthroplasty.
      Reported complications of this procedure include shortening of the extremity and
      ambulation difficulties requiring assistive devices. We report a case of an
      unusual finding of an ipsilateral femoral shaft fracture after a ground level
      fall 4 months after a resection arthroplasty for a septic hip. A closed reduction
      with internal fixation using an intramedullary nail was performed, and 3 months
      postoperatively, the patient was ambulating with device assistance.

PMID- 22386609
TI  - Total hip arthroplasty in adolescents with severe hip arthropathy and dysplasia
      associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.
AB  - Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare
      disorder. Patients with this syndrome experience early symptomatic arthropathy of
      the hips. We report a case of adolescent siblings with bilateral arthropathy
      associated with CACP syndrome in which total hip arthroplasty was performed as
      treatment of severe associated disability. Postoperative Harris Hip Scores for
      patient 1 were 86 for the right at 18 months and 96 for the left at 12 months.
      Postoperative Harris Hip Score at 6 months for patient 2 was 53; however, he had
      good range of motion and lacked deformity. Based on our limited experience and
      the limited available clinical data, we feel that total hip arthroplasty is a
      reasonable treatment option for adolescents with debilitating hip arthropathy
      associated with CACP syndrome.

PMID- 22386610
TI  - Retrospective evaluation of inpatient celecoxib use after total hip and knee
      arthroplasty at a Veterans Affairs Medical Center.
AB  - A retrospective cohort study (1.5 years) was performed to investigate the
      efficacy of celecoxib vs non-celecoxib use in patient who underwent total knee
      arthroplasty (TKA) and total hip arthroplasty (THA). Study time frame encompassed
      a pre and post period of a local policy decision opening access to short-term
      celecoxib use after TKA/THA. Primary end point was the amount of opioid use
      during their inpatient stay postprocedure. The TKA (n = 81) and THA (n = 60)
      groups were analyzed independently. Both celecoxib groups used significantly less
      opioids during their inpatient stay vs noncelecoxib groups, given in oral
      morphine milligram equivalents (TKA: 203 vs 337 mg, P = .002; THA: 214 vs 336 mg,
      P = .005). Other secondary outcome measures showed that the celecoxib groups also
      reported reduction in pain scores, total as needed (PRN) opioid doses, PRN opioid
      doses per day, average dose of PRN opioids, total PRN opioids, use of intravenous
      opioids, and rehabilitation facility admissions (in the TKA group only). Linear
      regression analysis showed a statistically significant inverse relationship
      between opioid consumption and age. Short-term celecoxib use after TKA/THA may
      lead to a reduction in overall opioid use and improved pain scores; however,
      further studies will be required to validate the results of this study.

PMID- 22386611
TI  - Periprosthetic joint infection: are patients with multiple prosthetic joints at
      risk?
AB  - Patients who present with a periprosthetic joint infection in a single joint may
      have multiple prosthetic joints. The risk of these patients developing a
      subsequent infection in another prosthetic joint is unknown. Our purposes were
      (1) to identify the risk of developing a subsequent infection in another
      prosthetic joint and (2) to describe the time span and organism profile to the
      second prosthetic infection. We retrospectively identified 55 patients with
      periprosthetic joint infection who had another prosthetic joint in place at the
      time of presentation. Of the 55 patients, 11 (20%) developed a periprosthetic
      joint infection in a second joint. The type of organism was the same as the first
      infection in 4 (36%) of 11 patients. The time to developing a second infection
      averaged 2.0 years (range, 0-6.9 years).

PMID- 22386612
TI  - Contribution of dynamic calibration to the measurement accuracy of a pressure
      plate system throughout the stance phase in sound horses.
AB  - The aim of this study was to evaluate the accuracy of the vertical force curve of
      a pressure plate (PP) using dynamic calibration with a force plate (FP) in six
      sound Warmblood horses. The animals were walked and trotted over a combined PP-FP
      system sampling at 250 Hz. Five valid measurements of each forelimb were
      collected. The recalibration factor (RF), the ratio between the calibrated and
      raw PP data, was evaluated in each timeframe throughout the stance phase.
      Following dynamic calibration, the vertical force curve of the PP demonstrated a
      characteristic biphasic pattern at the walk and typical spikes at the beginning
      and end of stance at the trot. Both at walk and trot, the RF was considerably
      higher and more variable in the first 5% of stance (i.e. the impact phase) and
      during the final 20% of stance (i.e. the breakover phase), whereas between these
      phases (i.e. in the support phase), the RF was lower and remained relatively
      constant. These findings were confirmed by plotting the RF as a function of the
      vertical force and the RF in the loading part of the vertical force curve was
      lower than in the unloading part of the curve. Without dynamic calibration with a
      FP, the accuracy of the PP appears suboptimal, especially at the impact and
      breakover phases. However, the accuracy of the PP was relatively high and
      constant during the support phase, and higher loading was not associated with
      increasing deviation. It is therefore essential to optimise PP calibration, as
      this may downsize systematic measuring errors. However, in a clinical setting,
      where a stand-alone PP is used to objectively quantify locomotor symmetry, these
      errors can be readily eliminated by evaluating left:right symmetry ratios.

PMID- 22386613
TI  - Textiloma mimicking a pericardial hydatid cyst: a case report.
AB  - Textiloma is unusual and uncommon diagnosis which is rarely considered. We report
      the case of a 13 year-old patient with Holt-Oram syndrome. He was operated on in
      2006 for ostium secundum atrial septal defect. The postoperative course was
      uneventful until 2010 when the child presented paroxysmal dyspnoea.
      Investigations revealed para-cardiac mass which was thought to be a hydatid cyst,
      but operative findings showed textiloma.

PMID- 22386614
TI  - Cardiac surgery in patients with a history of malignancy: increased complication
      rate but similar mortality.
AB  - BACKGROUND: Little is known about the outcome of cardiac surgery in patients with
      a prior history of malignancy. Our aim was to investigate in our unit the
      population of patients with a known malignancy and compare their outcomes to a
      matched population without malignancy. METHODS: We identified all patients who
      underwent cardiac surgery at the Alfred Hospital between February 2002 and
      December 2009 with malignancy. Cases were matched to 216 controls based on age,
      gender, major medical comorbidities and type of surgery. A univariate analysis
      was performed with Fishers exact test and chi(2) test. RESULTS: 83/4474 patients
      were identified with malignancy. Sixty-four (77%) were male. Mean age of the
      patients with malignancy was 66.7 years, and 67.4 in the control group. 68.7% had
      a solid organ tumour, and 31.3% had a haematological malignancy. There were no
      significant between-group differences in hospital or 30-day mortality. However,
      there were significantly higher rates of transfusion (79.5% vs 49%, p<0.0001),
      reintubation (8.4% vs 0.9%, p=0.0009), pneumonia (14.5% vs 6%, p=0.035),
      septicaemia (8.4% vs 1.9%, p=0.018), arrhythmias (42.2% vs. 33.8%, p=0.047) and
      anticoagulant complications (7.2% vs 0%, p=0.008) in patients with malignancies.
      CONCLUSION: Patients who present for cardiac surgery having had prior treatment
      for cancer are at particular risk for complications. However, these patients can
      be operated upon with acceptable risk. There is no difference in the short term
      mortality. Therefore, for selected patients who are undergoing curative treatment
      for their malignancy, or are in remission, cardiac surgery is not
      contraindicated.

PMID- 22386615
TI  - Internal displacement and health among the Palestinian minority in Israel.
AB  - Long term health impacts of internal displacement (ID) resulting from political
      violence are not well documented or understood. One such case is the ID of
      300,000-420,000 Palestinian citizens of Israel and their descendants during the
      Nakba of 1948 (Palestinian Catastrophe). We aim to document the long term health
      impacts of this ID. We draw on data collected in 2005 from a nationwide random
      sample of 902 individuals aged 30-70. Research participants were interviewed in
      person after being selected through a multistage sampling procedure. About 24% of
      participants reported that either they or their families had been internally
      displaced. Palestinian internally displaced persons (IDPs), that is, those who
      were forcibly displaced and dispossessed from their homes and lands during the
      Nakba and its aftermath, as well as their families and descendants, and who
      reside within the current borders of Israel, had an odds ratio of 1.45 (95% CI =
      1.02-2.07) for poor self-rated health (SRH) compared to non-IDPs after
      controlling for demographic, socioeconomic and psychosocial factors. No
      difference was found between IDPs and non-IDPs in limiting longstanding illness
      following control for confounders. Low socioeconomic position and chronic stress
      were significantly related to ID and to SRH. Our findings suggest adverse long
      term health impacts of the Nakba on the IDPs when compared to non-IDPs. We
      propose that these disparities might stem from IDPs' unhealed post-traumatic
      scars from the Nakba, or from becoming a marginalized minority within their own
      society due to their displacement and loss of collective identity. Given these
      long term health consequences, we conclude that displacement should be addressed
      with health and social policies for IDPs.

PMID- 22386617
TI  - More than culture: structural racism, intersectionality theory, and immigrant
      health.
AB  - Explanations for immigrant health outcomes often invoke culture through the use
      of the concept of acculturation. The over reliance on cultural explanations for
      immigrant health outcomes has been the topic of growing debate, with the critics'
      main concern being that such explanations obscure the impact of structural
      factors on immigrant health disparities. In this paper, we highlight the
      shortcomings of cultural explanations as currently employed in the health
      literature, and argue for a shift from individual culture-based frameworks, to
      perspectives that address how multiple dimensions of inequality intersect to
      impact health outcomes. Based on our review of the literature, we suggest
      specific lines of inquiry regarding immigrants' experiences with day-to-day
      discrimination, as well as on the roles that place and immigration policies play
      in shaping immigrant health outcomes. The paper concludes with suggestions for
      integrating intersectionality theory in future research on immigrant health.

PMID- 22386616
TI  - Neighborhood drug markets: a risk environment for bacterial sexually transmitted
      infections among urban youth.
AB  - We hypothesized that neighborhoods with drug markets, as compared to those
      without, have a greater concentration of infected sex partners, i.e. core
      transmitters, and that in these areas, there is an increased risk environment for
      STIs. This study determined if neighborhood drug markets were associated with a
      high-risk sex partnership and, separately, with a current bacterial STI
      (chlamydia and/or gonorrhea) after controlling for individual demographic and
      sexual risk factors among a household sample of young people in Baltimore City,
      MD. Analyses also tested whether links were independent of neighborhood
      socioeconomic status. Data for this study were collected from a household study,
      systematic social observations and police arrest, public health STI surveillance
      and U.S. census data. Nonlinear multilevel models showed that living in
      neighborhoods with household survey-reported drug markets increased the
      likelihood of having a high-risk sex partnership after controlling for individual
      level demographic factors and illicit drug use and neighborhood socioeconomic
      status. Further, living in neighborhoods with survey-reported drug markets
      increased the likelihood of having a current bacterial STI after controlling for
      individual-level demographic and sexual risk factors and neighborhood
      socioeconomic status. The results suggest that local conditions in neighborhoods
      with drug markets may play an important role in setting-up risk environments for
      high-risk sex partnerships and bacterial STIs. Patterns observed appeared
      dependent on the type of drug market indicator used. Future studies should
      explore how conditions in areas with local drug markets may alter sexual networks
      structures and whether specific types of drug markets are particularly important
      in determining STI risk.

PMID- 22386618
TI  - Stationarity in moment closure and quasi-stationarity of the SIS model.
AB  - Previous epidemiological studies on SIS model have only considered the dynamic
      evolution of the mean value and the variance of the infected individuals. In this
      paper, through cumulant neglection, we use the dynamic equations of all the
      moments of infected individuals to develop a recursive method to compute the
      equilibria manifold of the moment closure ODE's. Specifically, we use the stable
      equilibria of the moment closure ODE's to obtain good approximations of the quasi
      stationary states of the SIS model. This is a crucial step when the quasi
      stationary distribution is highly skewed.

PMID- 22386619
TI  - Fear of crime and psychological and physical abuse associated with ill health in
      a Swedish population aged 65-84 years.
AB  - OBJECTIVES: To assess the association between fear of crime and/or psychological
      and/or physical abuse in relation to self-reported physical and psychological
      health, using a large representative sample of elderly women and men in Sweden.
      STUDY DESIGN: Cross-sectional national survey. METHODS: Data were taken from a
      nationwide representative public health survey (2006). Men and women between the
      ages of 65 and 84 years were selected for the present analyses (4386 men and 4974
      women). The response rate for this age group was 59% for men and 70% for women.
      RESULTS: Psychological and physical abuse against elderly women and men led to
      higher odds ratios for negative health outcomes, independently of socio-economic
      status. Strong correlation was found between psychological abuse and negative
      health outcomes in both men and women, while the correlation was less strong for
      physical abuse, especially among women. The men had high odds ratios for suicidal
      thoughts and even for attempted suicide in connection with physical and
      psychological abuse and fear of crime. CONCLUSIONS: The study provides
      representative results addressing an extensive negative health outcome panorama
      caused by fear of crime and exposure to abuse.

PMID- 22386620
TI  - Persistent regional variation in treatment of hypertension.
AB  - OBJECTIVES: To assess regional variation within England in the proportion of
      people with survey-defined hypertension who were on treatment, and hypothesize if
      this was due to chance or confounding. STUDY DESIGN: Data from three annual,
      cross-sectional health examination surveys, the Health Survey for England.
      METHODS: Nationally representative random samples of the free-living general
      population were visited by an interviewer and a nurse. Blood pressure was
      measured with an automated monitor using a standardized protocol (2005: n = 5321,
      2006: n = 10,213, 2007: n = 4848). Hypertension was defined as systolic blood
      pressure >=140 mmHg, diastolic blood pressure >=90 mmHg, and/or taking prescribed
      medication to lower blood pressure. RESULTS: In London, a higher proportion of
      participants with survey-defined hypertension were on anti-hypertensive
      medication in each separate year's sample compared with the rest of England [2005
      2007 average: 61% men, 66% women in London; 43% men, 55% women in England (P for
      London vs rest of England <0.001 for each sex)]. Regression analysis showed that
      this regional effect [odds ratio (OR) 1.47 95% confidence interval (CI) 1.94
      2.47, P = 0.031] was no longer significant after adjustment for demographic and
      socio-economic factors (OR 1.37, 95% CI 0.94-1.98, P = 0.101), but was
      strengthened (OR 1.69, 95% CI 1.09-2.60, P = 0.018) by including longstanding
      illness, diabetes, cardiovascular disease and health behaviours in the model.
      CONCLUSIONS: The proportion of hypertensive patients on anti-hypertensive
      medication was consistently above the national average in London, and this was
      associated with personal characteristics. Comorbidities increased the effect,
      even after adjustment for personal characteristics. This result may be due to
      greater population mobility in London, with more people having new patient health
      checks. Understanding this variation could enhance treatment nationally and
      internationally.

PMID- 22386621
TI  - Visualizing macromolecular complexes with in situ liquid scanning transmission
      electron microscopy.
AB  - A central focus of biological research is understanding the structure/function
      relationship of macromolecular protein complexes. Yet conventional transmission
      electron microscopy techniques are limited to static observations. Here we
      present the first direct images of purified macromolecular protein complexes
      using in situ liquid scanning transmission electron microscopy. Our results
      establish the capability of this technique for visualizing the interface between
      biology and nanotechnology with high fidelity while also probing the interactions
      of biomolecules within solution. This method represents an important advancement
      towards allowing future high-resolution observations of biological processes and
      conformational dynamics in real-time.

PMID- 22386622
TI  - Sensitivity to chemoradiation predicts development of metastasis in muscle
      invasive bladder cancer patients.
AB  - OBJECTIVES: In bladder-sparing approaches for muscle-invasive bladder cancer
      (MIBC) involving transurethral resection of the bladder tumor (TURBT) and
      chemoradiation, survival outcomes are excellent for patients who achieve tumor
      free state after TURBT and chemoradiation but poor for those with persistent
      disease. Since metastatic disease accounts for most bladder cancer deaths, we
      hypothesized that tumor sensitivity to chemoradiation may reflect metastatic
      potential in MIBC. MATERIALS AND METHODS: From 1997 to 2010, 179 cT2-4aN0M0
      bladder cancer patients underwent TURBT and induction chemoradiation (40 Gy with
      cisplatin 20 mg/d for 5 days * 2). Study subjects were 73 patients who had had
      macroscopic disease after TURBT and were evaluated for tumor sensitivity to the
      induction chemoradiation; of the 73 patients, chemoradiation response was
      evaluated pathologically in partial and radical cystectomy specimens for 8 and 44
      patients, respectively, and clinically for the remaining 21 who did not undergo
      cystectomy. Tumors were defined as chemoradiation-sensitive when they regressed
      to T0 pathologically for the 52 patients undergoing cystectomy or clinically for
      the 21 undergoing no cystectomy; otherwise, they were defined as chemoradiation
      resistant. Primary and secondary endpoints were metastasis-free and cancer
      specific survival, respectively. The association between chemoradiation
      sensitivity and development of metastasis was investigated in MIBC patients.
      RESULTS: Of the 73 patients, 21 (29%: 13 pathologic and 8 clinical T0) had
      chemoradiation-sensitive tumors while 52 (71%) had chemoradiation-resistant
      tumors. Median follow-up was 53 months. Multivariate analysis identified
      chemoradiation resistance as the strongest independent predictor for the
      development of metastasis (hazard ratio (HR) 18.9, P < 0.0001). When stratified
      by chemoradiation sensitivity, 5-year metastasis-free and cancer-specific
      survival rates were 94.7% and 100%, respectively, for patients with
      chemoradiation-sensitive tumors, and 45.7% (P = 0.0005) and 41.0% (P < 0.0001),
      respectively, for patients with chemoradiation-resistant tumors. CONCLUSIONS:
      Chemoradiation sensitivity predicts the development of metastasis in bladder
      cancer. Clinical and translational research results indicate that chemoradiation
      sensitivity is likely to reflect metastatic potential.

PMID- 22386623
TI  - Two decades' experience with a prospective biobank for urologic oncology:
      research, clinical care, and the patients' view.
AB  - OBJECTIVES: Collection of clinical data and associated tissue samples has become
      an essential tool for oncologic research. Since 1990, efforts have been ongoing
      to implement prospective documentation of all oncologic cases in our department
      accompanied by a special aftercare program ensuring regular visits and reliable
      data acquisition. MATERIALS AND METHODS: Our prospective database comprises a
      total of 6,567 cases covering all types of urologic malignancies: prostate
      (40.7%), renal (30.5%), urothelial (21.8%), testicular (5.8%), penile (0.8%), and
      other (0.4%). A specialized full-time documentalist supported by 3 student
      assistants entered 38,135 aftercare visits characterized by approximately 100
      partly disease-specific items. The Institute of Pathology's general collection
      contains more than 6 million paraffin-embedded samples, and since 2005 the
      interdisciplinary Tissue Bank at the National Center for Tumor Diseases in
      Heidelberg has collected about 21,000 cryo-samples. Furthermore, we asked the
      opinion of 158 patients who attended our clinic for cancer surgery using a self
      designed questionnaire. RESULTS: Of 158 patients asked to be included in the
      biobank, from 09/07 through 02/08, none refused. Their additional questionnaire
      had a return rate of 81% (n = 128). Moral obligation for supporting medical
      research was realized by 95%, and circumstantial pressure to participate was not
      a relevant factor for 87%. Whereas only 68% were hoping for personal benefit,
      altruism seemed to be a much stronger motive: 96% believe others could be healed
      because of further medical progress; 93% wanted to be actively informed about
      recommended aftercare visits. Consequently, response rates in the "Heidelberg
      Cancer Maintenance Program" are constantly above 93%. Regarding research, a total
      of 144 scientific inquiries have been answered using our database since 1995.
      Within the last 5 years, 37 manuscripts originated from biobank data: herein,
      molecular markers and risk factors have been correlated with clinical outcome.
      Additionally, TNM-validation studies were conducted. CONCLUSIONS: Prospective
      collection of clinical data and corresponding tissue has become an indispensable
      research tool in oncology. In general, patients do not object tissue banking and
      embrace special aftercare programs.

PMID- 22386624
TI  - How robust is human gait to muscle weakness?
AB  - Humans have a remarkable capacity to perform complex movements requiring agility,
      timing, and strength. Disuse, aging, and disease can lead to a loss of muscle
      strength, which frequently limits the performance of motor tasks. It is unknown,
      however, how much weakness can be tolerated before normal daily activities become
      impaired. This study examines the extent to which lower limb muscles can be
      weakened before normal walking is affected. We developed muscle-driven
      simulations of normal walking and then progressively weakened all major muscle
      groups, one at the time and simultaneously, to evaluate how much weakness could
      be tolerated before execution of normal gait became impossible. We further
      examined the compensations that arose as a result of weakening muscles. Our
      simulations revealed that normal walking is remarkably robust to weakness of some
      muscles but sensitive to weakness of others. Gait appears most robust to weakness
      of hip and knee extensors, which can tolerate weakness well and without a
      substantial increase in muscle stress. In contrast, gait is most sensitive to
      weakness of plantarflexors, hip abductors, and hip flexors. Weakness of
      individual muscles results in increased activation of the weak muscle, and in
      compensatory activation of other muscles. These compensations are generally
      inefficient, and generate unbalanced joint moments that require compensatory
      activation in yet other muscles. As a result, total muscle activation increases
      with weakness as does the cost of walking. By clarifying which muscles are
      critical to maintaining normal gait, our results provide important insights for
      developing therapies to prevent or improve gait pathology.

PMID- 22386625
TI  - Biotransformation of sophoricoside in Fructus sophorae by the fungus
      Schizophyllum commune.
AB  - Biotransformation of sophoricoside in Fructus sophorae was performed with
      Schizophyllum commune. Sophoricoside was firstly metabolized to 4',5,7
      trihydroxyisoflavone (2), and then to 4',7-dihydroxy-5-methoxyisoflavone (3) and
      5,7-dihydroxy-4'-methoxyisoflavone (4) as determined by NMR and MS analyzes. The
      content of compound (2) was increased by more than 30-fold, and compound (3) is a
      new product that showed good cytotoxic activity with an IC(50) of 12.1 nmol/ml
      against MCF-7 cells.

PMID- 22386626
TI  - High concentration powdered activated carbon-membrane bioreactor (PAC-MBR) for
      slightly polluted surface water treatment at low temperature.
AB  - In this study, different concentrations of PAC combined with MBR were carried out
      to treat slightly polluted surface water (SPSW) at low temperature (10 degrees
      C). Effects of PAC on the efficiencies of operation, treatment, and the
      performance of the process were investigated. It was found that the effluent
      quality, performance efficiency, resistance of shock load were all enhanced and
      chemical irreversible membrane fouling was reduced with increasing dosage of PAC
      in MBR. Only when the concentration of PAC which acted as biological carriers was
      high enough (i.g., 50 g/L), nitrification without initial inoculation in the
      filtration tank could start within 19 days and be completed within 35 days at 10
      degrees C. Fifty grams per liter PAC was the optimal dosage in MBR for stable and
      extended operation. Under this condition, mean removal efficiencies of ammonia
      nitrogen (NH(3)-N), dissolved organic carbon (DOC) and UV(254) were 93%, 75%, and
      85%, respectively.

PMID- 22386627
TI  - Aqueous phase hydrogenolysis of glycerol to bio-propylene glycol over Pt-Sn
      catalysts.
AB  - PtSn supported on SiO(2) obtained via surface organometallic chemistry techniques
      catalyzes hydrogenolysis of glycerol to obtain bio-propylene glycol (PG).
      Bimetallic catalysts with Sn contents between 0.1% and 1% wt were carefully
      prepared by selective hydrogenolysis of Sn(n-C(4)H(9))(4) on Pt. TEM, TPR, H(2)
      and CO chemisorptions, and XPS studies have shown that tin selective deposition
      on the metallic phase is obtained. At 200 degrees C under N(2) or H(2) pressure,
      the presence of tin increases drastically: both the selectivity and the activity
      of the glycerol conversion into PG. During 2h batch runs; it could be observed
      that PtSn catalysts with Sn/Pt ratio=0.2 showed the best performance (PG
      selectivity=59% and 83% under N(2) and H(2) pressure respectively). The increase
      in activity and selectivity could be explained by the presence of Sn(+n) species
      "acid Lewis sites" which would facilitate the C-OH adsorption and its subsequent
      C-O cleavage favoring the propylene glycol production.

PMID- 22386628
TI  - Comparison of the effects of five pretreatment methods on enhancing the enzymatic
      digestibility and ethanol production from sweet sorghum bagasse.
AB  - To improve the enzymatic digestibility of sweet sorghum bagasse and bioethanol
      production, five pretreatment methods have been investigated and compared,
      including (1) dilute NaOH solution autoclaving pretreatment, (2) high
      concentration NaOH solution immersing pretreatment, (3) dilute NaOH solution
      autoclaving and H(2)O(2) immersing pretreatment, (4) alkaline peroxide
      pretreatment and (5) autoclaving pretreatment. Among them, the best result was
      obtained when sweet sorghum bagasse was dilute NaOH solution autoclaving and
      H(2)O(2) immersing pretreatment. The highest cellulose hydrolysis yield, total
      sugar yield and ethanol concentration were 74.29%, 90.94 g sugar/100g dry matter
      and 6.12 g/L, respectively, which were 5.88, 9.54 and 19.13 times higher than the
      control. Moreover, the FTIR and SEM analysis illustrated significant molecule and
      surface structure changes of the sweet sorghum bagasse after pretreatments.

PMID- 22386629
TI  - Performance and microbial diversity of microbial fuel cells coupled with
      different cathode types during simultaneous azo dye decolorization and
      electricity generation.
AB  - To study the effect of cathode type on performance and microbial diversity of the
      MFC, aerobic biocathode and air-cathode were incorporated into microbial fuel
      cells (MFCs) which were explored for simultaneous azo dye decolorization and
      electricity generation. The electrochemical impedance spectroscopy (EIS) results
      demonstrated that the catalytic activity of the microorganisms on the biocathode
      surface was comparable with that of the platinum coated on the air-cathode. The
      power density achieved by using biocathode was lower than air-cathode, but the
      biocathode could greatly improve the Congo red decolorization rate. By using the
      biocathode, 96.4% decolorization of Congo red was obtained within 29 h, whereas,
      about 107 h was required to achieve the same decolorization efficiency with the
      air-cathode. 16S rRNA sequencing analysis demonstrated a phylogenetic diversity
      in the communities of the anode biofilm and showed clear differences between the
      anode-attached populations in the MFCs with a different cathode type.

PMID- 22386630
TI  - Conversion of spent mushroom substrate to biofertilizer using a stress-tolerant
      phosphate-solubilizing Pichia farinose FL7.
AB  - To develop high-efficient biofertilizer, an environmental stress-tolerant
      phosphate-solubilizing microorganism (PSM) was isolated from agricultural wastes
      compost, and then applied to spent mushroom substrate (SMS). The isolate FL7 was
      identified as Pichia farinose with resistance against multiple environmental
      stresses, including 5-45 degrees C temperature, 3-10 pH range, 0-23% (w/v) NaCl
      and 0-6M ammonium ion. Under the optimized cultivation condition, 852.8 mg/l
      total organic acids can be produced and pH can be reduced to 3.8 after 60 h,
      meanwhile, the soluble phosphate content reached 816.16 mg/l. The P. farinose was
      used to convert SMS to a phosphate biofertilizer through a semi-solid
      fermentation (SSF) process. After fermentation of 10 days, cell density can be
      increased to 5.6 * 10(8)CFU/g in biomass and pH in this medium can be decreased
      to 4.0. SMS biofertilizer produced by P. farinose significantly improved the
      growth of soybean in pot experiments, demonstrating a tremendous potential in
      agricultural application.

PMID- 22386631
TI  - Genetic resources of extremotolerant fungi: a method for identification of genes
      conferring stress tolerance.
AB  - Fungal species from extreme environments represent an underexploited source of
      stress-resistance genes. These genes have the potential to improve stress
      tolerance of economically important microorganisms and crops. An efficient high
      throughput method for the identification of biotechnologically interesting genes
      of extremotolerant fungi was developed by constructing a cDNA expression library
      in Saccharomyces cerevisiae and screening for gain-of-function transformants
      under stress conditions. The advantages and possible modifications of this method
      are discussed, and its efficiency is demonstrated using the stress-tolerant
      basidiomycetous yeast Rhodotorula mucilaginosa. Twelve R. mucilaginosa genes are
      described that increase halotolerance in S. cerevisiae. These include genes
      encoding a phosphoglucomutase and a phosphomannomutase. All 12 investigated genes
      might be useful for the improvement of halotolerance in genetically modified
      crops or industrial microorganisms.

PMID- 22386632
TI  - A functional 5-HT1A variant and comorbid anxiety.

PMID- 22386633
TI  - Satisfaction with antiepileptic drugs in children and adolescents with newly
      diagnosed and chronic epilepsy.
AB  - PURPOSE: To assess incidence, indicators and outcome of satisfaction with
      antiepileptic drugs in children. METHODS: Multicenter, observational, open,
      prospective survey of children and adolescents with epilepsy with three-month
      follow-up. Included were patients aged 3-17 years with newly diagnosed ("new
      diagnosis") or chronic epilepsy ("old diagnosis") requiring treatment start or
      change. Satisfaction was assessed with the Hedonic Visual Scale or direct
      questions, depending on patient's age. Quality of life of adolescents (QOLIE-48)
      and of caregivers (SF-36) and predictors of (dis)satisfaction were also assessed.
      RESULTS: 293 patients completed the study. Most had generalized idiopathic
      epilepsy, and a disease lasting <12 months. Newly diagnosed patients were 60.8%.
      Patients declaring satisfaction were 70.6% at one month and 75.8% at three
      months. Compared to old diagnosis, new diagnosis carried a higher satisfaction
      rate and improved satisfaction at end of follow-up. Independent predictors of
      dissatisfaction were an old diagnosis, adverse events and SF-36 score. The latter
      remained the only independent predictor of persisting dissatisfaction when
      adjusting for the presence of and the interaction with adverse events.
      CONCLUSIONS: About one-fourth of children and adolescents with epilepsy are
      dissatisfied with treatment. Chronic epilepsy, adverse events, and
      parents/caregivers with poor quality of life predict dissatisfaction.

PMID- 22386634
TI  - Febrile infection-related epilepsy syndrome is not caused by SCN1A mutations.
AB  - Two distinctive epileptic encephalopathies, febrile infection-related epilepsy
      syndrome (FIRES) and Dravet syndrome (DS), present with febrile status
      epilepticus in a normal child followed by refractory focal seizures and cognitive
      decline although there are differentiating features. Abnormalities of the sodium
      channel gene SCN1A are found in 75% of DS patients. We found no SCN1A mutations
      or copy number variants in 10 patients with FIRES. Other genetic etiologies
      deserve consideration.

PMID- 22386635
TI  - Body-specific representations of spatial location.
AB  - The body specificity hypothesis (Casasanto, 2009) posits that the way in which
      people interact with the world affects their mental representation of
      information. For instance, right- versus left-handedness affects the mental
      representation of affective valence, with right-handers categorically associating
      good with rightward areas and bad with leftward areas, and left-handers doing the
      opposite. In two experiments we test whether this hypothesis can: extend to
      spatial memory, be measured in a continuous manner, be predicted by extent of
      handedness, and how the application of such a heuristic might vary as a function
      of informational specificity. Experiment 1 demonstrates systematic and continuous
      spatial location memory biases as a function of associated affective information;
      right-handed individuals misremembered positively- and negatively-valenced
      locations as further right and left, respectively, relative to their original
      locations. Left-handed individuals did the opposite, and in general those with
      stronger right- or left-handedness showed greater spatial memory biases.
      Experiment 2 tested whether participants would show similar effects when studying
      a map with high visual specificity (i.e., zoomed in); they did not. Overall we
      support the hypothesis that handedness affects the coding of affective
      information, and better specify the scope and nature of body-specific effects on
      spatial memory.

PMID- 22386636
TI  - An analytic appraisal of nutrition screening tools supported by original data
      with particular reference to age.
AB  - OBJECTIVE: Controversies exist as to the suitability of various nutrition
      screening tools for various age groups, the incorporation of age and age-related
      criteria into some tools, and the procedures associated with tool selection.
      METHODS: Reviews of the literature and national and local datasets were used to
      identify the types of screening tools available for different age groups, the
      origins of age-related criteria, and the value of tool selection procedures based
      on predicting clinical outcomes. RESULTS: Nutrition screening can be undertaken
      in fetuses, children, and adults over narrow or wide age ranges, for diagnostic
      or prognostic purposes, with or without nutritional interventions. Certain tools
      can establish malnutrition risk without using any nutritional criteria, whereas
      others can do so only with nutritional criteria. The incorporation of age and age
      specific body mass index criteria into adult screening tools can influence the
      prevalence and age distribution of malnutrition, but no justification is usually
      provided for their use. In several circumstances, age alone can predict mortality
      and length of hospital stay much better than screening tools. We identified
      various methodologic problems in nutrition screening tool selection. CONCLUSIONS:
      A comparison of nutrition screening tools designed for different age groups and
      different purposes can be problematic. Age and screening tools incorporating risk
      factors that are non-modifiable or generally weakly modifiable by nutritional
      support (e.g., age, disease severity) may predict outcomes of disease, but they
      are not necessarily suitable for predicting outcomes of nutritional support. To
      contextualize the findings, a framework for screening tool selection is suggested
      that takes into account a matrix of needs.

PMID- 22386637
TI  - Beyond the barriers: racial discrimination and use of complementary and
      alternative medicine among Black Americans.
AB  - This article examines whether self-reported racial discrimination is associated
      with greater use of complementary and alternative medicine (CAM) and assesses
      whether the effects of reported racial discrimination are specific to the setting
      in which the unfair treatment occurred (i.e., medical or nonmedical settings).
      Data were drawn from the National Survey of Midlife Development in the United
      States (MIDUS) of Black adults aged 25 and older at baseline (N=201). Analyses
      account for multiple forms of discrimination: major lifetime discriminatory
      events and everyday discrimination (more commonplace negative occurrences). Using
      logistic and negative binomial regression, results reveal that racial
      discrimination was associated with a higher likelihood of using any type of CAM
      as well as using more modalities of CAM. Also, both discrimination in health care
      and discrimination in nonmedical contexts predicted greater use of CAM. The
      findings underscore the tenet that health care choices, while influenced by
      health status and availability of health care resources, are also shaped by
      perceived barriers. The experience of racial discrimination among Black people is
      associated with greater use of alternative means of health care, as a way to cope
      with the barriers they experience in institutional settings in the United States.

PMID- 22386638
TI  - Connections and consequences in complex systems: insights from a case study of
      the emergence and local impact of crisis resolution and home treatment services.
AB  - In this article the broad contours of a complexity perspective are outlined.
      Complexity ideas are then drawn on to frame an empirical examination of the
      connections running between different levels of organisation in health and social
      care, and to underpin investigation into the intended and unintended local system
      consequences of service development. Data are used from a study conducted in the
      UK's mental health field. Here, macro-level policy has led to the supplementing
      of longstanding community mental health teams by newer, more specialised,
      services. An example includes teams providing crisis resolution and home
      treatment (CRHT) care as an alternative to hospital admission. Using an embedded
      case study design, where 'the case' examined was a new CRHT team set in its
      surrounding organisational environment, ethnographic data (with interviews
      predominating) were generated in a single site in Wales over 18 months from the
      middle of 2007. In a large-scale context favourable to local decision-making, and
      against a background of a partial and disputed evidence base, the move to
      establish the new standalone service was contested. Whilst users valued the work
      of the team, and local practitioners recognised the quality of its contribution,
      powerful effects were also triggered across the locality's horizontal interfaces.
      Participants described parts of the interconnected system being closed to release
      resources, staff gravitating to new crisis services leaving holes elsewhere, and
      the most needy service users being cared for by the least experienced workers.
      Some community mental health team staff described unexpected increases in
      workload, and disputes over eligibility for crisis care with implications for
      system-wide working relations. Detailed data extracts are used to illustrate
      these connections and consequences. Concluding lessons are drawn on the use of
      evidence to inform policy, on the significance of local contexts and system
      interfaces, and on anticipating the unexpected at times of change. 

PMID- 22386639
TI  - Frames and counter-frames giving meaning to dementia: a framing analysis of media
      content.
AB  - Media tend to reinforce the stigmatization of dementia as one of the most dreaded
      diseases in western society, which may have repercussions on the quality of life
      of those with the illness. The persons with dementia, but also those around them
      become imbued with the idea that life comes to an end as soon as the diagnosis is
      pronounced. The aim of this paper is to understand the dominant images related to
      dementia by means of an inductive framing analysis. The sample is composed of
      newspaper articles from six Belgian newspapers (2008-2010) and a convenience
      sample of popular images of the condition in movies, documentaries, literature
      and health care communications. The results demonstrate that the most dominant
      frame postulates that a human being is composed of two distinct parts: a material
      body and an immaterial mind. If this frame is used, the person with dementia ends
      up with no identity, which is in opposition to the Western ideals of personal
      self-fulfilment and individualism. For each dominant frame an alternative counter
      frame is defined. It is concluded that the relative absence of counter-frames
      confirms the negative image of dementia. The inventory might be a help for
      caregivers and other professionals who want to evaluate their communication
      strategy. It is discussed that a more resolute use of counter-frames in
      communication about dementia might mitigate the stigma that surrounds dementia.

PMID- 22386640
TI  - Capsulorhexis rescue after peripheral radial tear-out: quick-pull technique.
AB  - We describe a technique to rescue the continuous curvilinear capsulorhexis (CCC)
      in cases in which complete radial tears make it impossible to use normal traction
      forceps. A circumferential path and rapid movement are applied in the plane of
      the anterior capsule in the direction of the center pupil. This technique was
      used in 50 cases. In 47, the CCC could be completed; in 3, it could not and
      surgery was continued with low-parameter phacoemulsification. No other
      intraoperative complications occurred. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 22386642
TI  - Body mass index and the development of amiodarone-induced thyrotoxicosis in
      adults with congenital heart disease--a cohort study.
AB  - INTRODUCTION: Amiodarone-induced thyrotoxicosis (AIT) is a recognized
      complication of amiodarone treatment with limited management options. Its
      predisposing factors are incompletely defined yet a higher prevalence was
      reported in adults with congenital heart disease (CHD). Therefore we sought to
      determine the incidence and risk factors for AIT in adults with CHD. METHODS: At
      a tertiary care center we followed a historical cohort of amiodarone-treated CHD
      patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with
      last thyroid assessment on amiodarone. Cumulative incidence of AIT was
      calculated. AIT association with nutritional status was hypothesized a priori.
      RESULTS: AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in
      the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO
      initiation compared with the rest of the cohort (mean +/- standard deviation:
      21.9 +/- 2.9 vs. 25.1 +/- 5.0; p<0.001). Patients with BMI<21 were more likely to
      develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence
      of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients
      had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%,
      p=0.059). On multivariate analysis body mass index and goiter remained
      independent predictors of outcome. CONCLUSIONS: BMI<21 at initiation of
      amiodarone therapy and presence of goiter are strong predictors of AIT in this
      population. Its incidence is time dependent. These predictors can be used
      clinically in assessing overall impact of amiodarone therapy in congenital heart
      disease patients.

PMID- 22386641
TI  - Sculpting the hippocampus from within: stress, spines, and CRH.
AB  - Learning and memory processes carried out within the hippocampus are influenced
      by stress in a complex manner, and the mechanisms by which stress modulates the
      physiology of the hippocampus are not fully understood. This review addresses how
      the production and release of the neuropeptide corticotropin-releasing hormone
      (CRH) within the hippocampus during stress influences neuronal structure and
      hippocampal function. CRH functions in the contexts of acute and chronic stresses
      taking place during development, adulthood and aging. Current challenges are to
      uncover how the dynamic actions of CRH integrate with the well-established roles
      of adrenal-derived steroid stress hormones to shape the cognitive functions of
      the hippocampus in response to stress.

PMID- 22386643
TI  - All cut up! The consequences of calpain activation on platelet function.
AB  - The Ca(2+)-activated proteases or calpains, play a crucial role in a spectrum of
      physiological processes such as cytoskeletal remodeling, cellular signaling, cell
      migration, apoptosis, cell survival and platelet activation, by the proteolytic
      cleavage of target proteins. Rather than eliciting protein degradation the
      calpains are responsible for their modification (e.g. activation, inhibition or
      altered sensitivity to intracellular signals) and therefore make a significant
      impact on intracellular signaling. Maintained calpain activation is known to be
      associated with disease development and in platelet calpains are involved in both
      physiological platelet activation as well as pathological platelet hyper
      activation.

PMID- 22386644
TI  - Altered expression of immune-associated genes in first-trimester human decidua of
      pregnancies later complicated with hypertension or foetal growth restriction.
AB  - During pregnancy the maternal immune system has to coordinate uterine spiral
      artery remodelling, trophoblast invasion, and acceptance of the semi-allogenic
      fetus simultaneously. As dysregulation of the immune system is associated with
      adverse pregnancy outcomes, we analysed first-trimester deciduas of pregnancies
      for immune parameters in later complicated pregnancies. Higher IL6 and macrophage
      mRNA expression, and lower ratios of regulatory macrophages were found in first
      trimester deciduas of pregnancies later complicated with pregnancy-induced
      hypertension. Lower Gata3 (Th2) mRNA expression was found in deciduas of
      pregnancies with later foetal growth restriction. Our results suggest that
      adverse pregnancy outcomes are associated with immunological disturbances in
      first-trimester deciduas.

PMID- 22386645
TI  - Compressive sampling with prior information in remotely detected MRI of
      microfluidic devices.
AB  - The design and operation of microfluidic analytical devices depends critically on
      tools to probe microscale chemistry and flow dynamics. Magnetic resonance imaging
      (MRI) seems ideally suited to this task, but its sensitivity is compromised
      because the fluid-containing channels in "lab on a chip" devices occupy only a
      small fraction of the enclosing detector's volume; as a result, the few
      microfluidic applications of NMR have required custom-designed chips harboring
      many detectors at specific points of interest. To overcome this limitation, we
      have developed remotely detected microfluidic MRI, in which an MR image is stored
      in the phase and intensity of each analyte's NMR signal and sensitively detected
      by a single, volume-matched detector at the device outflow, and combined it with
      compressed sensing for rapid image acquisition. Here, we build upon our previous
      work and introduce a method that incorporates our prior knowledge of the
      microfluidic device geometry to further decrease acquisition times. We
      demonstrate its use in multidimensional velocimetric imaging of a microfluidic
      mixer, acquiring microscopically detailed images 128 times faster than is
      possible with conventional sampling. This prior information also informs our
      choice of sampling schedule, resulting in a scheme that is optimized for a
      specific flow geometry. Finally, we test our approach in synthetic data and
      explore potential reconstruction errors as a function of optimization and
      reconstruction parameters.

PMID- 22386646
TI  - W-band PELDOR with 1 kW microwave power: molecular geometry, flexibility and
      exchange coupling.
AB  - A technique that is increasingly being used to determine the structure and
      conformational flexibility of biomacromolecules is Pulsed Electron-Electron
      Double Resonance (PELDOR or DEER), an Electron Paramagnetic Resonance (EPR) based
      technique. At X-band frequencies (9.5 GHz), PELDOR is capable of precisely
      measuring distances in the range of 1.5-8 nm between paramagnetic centres but the
      orientation selectivity is weak. In contrast, working at higher frequencies
      increases the orientation selection but usually at the expense of decreased
      microwave power and PELDOR modulation depth. Here it is shown that a home-built
      high-power pulsed W-band EPR spectrometer (HiPER) with a large instantaneous
      bandwidth enables one to achieve PELDOR data with a high degree of orientation
      selectivity and large modulation depths. We demonstrate a measurement methodology
      that gives a set of PELDOR time traces that yield highly constrained data sets.
      Simulating the resulting time traces provides a deeper insight into the
      conformational flexibility and exchange coupling of three bisnitroxide model
      systems. These measurements provide strong evidence that W-band PELDOR may prove
      to be an accurate and quantitative tool in assessing the relative orientations of
      nitroxide spin labels and to correlate those orientations to the underlying
      biological structure and dynamics.

PMID- 22386647
TI  - Liquid state Dynamic Nuclear Polarization probe with Fabry-Perot resonator at 9.2
      T.
AB  - Recent achievements in liquid state DNP at high magnetic fields showing
      significant enhancements on aqueous solutions have initiated strong interest in
      possible applications of this method to biomolecular research. However, in situ
      DNP of biomolecules at ambient temperatures is a challenging task due to high
      microwave losses leading to excessive sample heating. To avoid such heating the
      sample volume has to be reduced strongly to keep it away from the electric
      component of the microwave field. A helical double resonance structure, used for
      the first demonstrations of the applicability of Overhauser DNP to aqueous
      solutions at high magnetic fields (9.2 T), restricted the sample size to a very
      small volume of 2 nl. Together with a poor spectral resolution this resulted in
      small overall signal amplitude, hampering observations of biomolecules. Here we
      present a new type of the double resonance structure for liquid-state DNP which
      consists of a Fabry-Perot resonator for the microwave excitation and a stripline
      resonator for the NMR detection. This new double resonance structure (260 GHz/400
      MHz) offers a 30-fold increase in aqueous sample volume (80 nl) with respect to
      the helical probe and exhibits improved NMR sensitivity and linewidth.

PMID- 22386648
TI  - Oral thromboprophylaxis following total hip replacement: the issue of compliance.
AB  - INTRODUCTION: Thirty-five to 40 days' thromboprophylaxis is recommended following
      total hip replacement (THR). Low molecular weight heparin (LMWH) injected by a
      health professional ensures good compliance. Compliance with recent oral
      anticoagulants has not been precisely assessed. Oral self-administration, without
      coagulation monitoring tests, may be a worrying issue in the management of what
      is a potentially catastrophic adverse event, without prodromal symptoms alerting
      the patient to the need for regular intake throughout the prescription period.
      HYPOTHESIS: It was hypothesized that compliance with these new oral
      anticoagulants is good over the entire treatment period. PATIENTS AND METHOD: The
      present cohort study prospectively assessed compliance with oral medication (two
      capsules of dabigatran etexilate [Pradaxa((r))] per day in a single dose at a set
      time) following THR. An electronic device continuously monitored the day and time
      of extraction of capsules from the package. All included patients underwent
      clinical and echo-Doppler examination at day 30+/-5 after the start of the study.
      RESULTS: Fifty-six patients were included at their discharge home. Overall
      compliance was 98.1% (3,188/3246 capsules correctly taken), falling off slightly
      over time but never below 97.1%. One patient was diagnosed with symptomatic
      thrombophlebitis 34 days postoperatively, associated with non-compliance at day
      11. End of follow-up echo-Doppler found four cases of asymptomatic distal venous
      thrombosis. There were no hemorrhagic complications. DISCUSSION: The risk of
      thromboembolic complications diminishes over time, while oral anticoagulants have
      a wide therapeutic window and relatively long half-life (15-17 hrs). Efficacy was
      demonstrated, with improved patient comfort and cost-saving. Compliance in the
      present series was satisfactory. This, however, should not mean that patients not
      be appropriately informed, as in the present study, so as to improve compliance.
      LEVEL OF EVIDENCE: Level III, prospective diagnostic.

PMID- 22386649
TI  - [Development and validation of indicators relating to the quality of prevention
      and early management of postpartum haemorrhage (COMPAQ-HPST research project)].
AB  - OBJECTIVES: To develop and validate a set of quality indicators (QIs) relating to
      the prevention and early management of postpartum haemorrhage (PPH) in maternity
      wards. The ultimate aim was to use these QIs for hospital comparison and public
      diffusion of results. MATERIALS AND METHODS: In 2009, COMPAQ-HPST developed a set
      of five QIs from consensus guidelines with the aid of experts and professional
      associations, relating to: i) the prevention of PH (three QIs) and ii) the
      initial management of PPH (two QIs). We also tested a questionnaire about the
      presence of written protocols in maternity wards. RESULTS: Ninety-seven voluntary
      maternity wards were included in the study. All five QIs showed wide variations
      in implementation among hospitals, revealing substantial room for improvement.
      Results of the questionnaire were variable according to the item considered.
      CONCLUSION: We validated five process QIs relating to the prevention and early
      management of PPH. All these five QIs have been transmitted to HAS for nationwide
      generalization. They should allow hospitals to implement quality of care
      improvement in this setting, adapted to their individual and comparative results.

PMID- 22386650
TI  - Ghrelin promotes the differentiation of human embryonic stem cells in infarcted
      cardiac microenvironment.
AB  - Ghrelin is broadly expressed in myocardial tissues, where it exerts different
      functions. It also has been found to have a wide variety of biological functions
      on cell differentiation and tissue development. The aim of this study was to
      investigate the effect of ghrelin on human embryonic stem cell (hESC)
      differentiation in infarcted cardiac microenvironment. The hESCs grown on feeder
      layers expressed several pluripotential markers including alkaline phosphatase
      (AKP). Four weeks after transplantation into rat infarcted hearts, the hESCs and
      their progeny cells survived and formed intracardiac grafts were 54.7% and 19.6%
      respectively in ghrelin- and phosphate-buffered saline (PBS)-treated groups.
      Double immunostaining with anti-human Sox9 and anti-HNA or anti-human fetal liver
      kinase-1 (Flk1) and anti beta-tubulin showed that the human grafts were in
      development. However, double positive stains were only found in the ghrelin
      treated group. In addition, the hESC injection protocol was insufficient to
      restore heart function of the acute myocardial infarction model. Our study,
      therefore, provides a new insight of ghrelin on promoting hESC survival and
      differentiation in rat infarcted cardiac microenvironment. This may give a clue
      for therapy for myocardial infarction by hESCs or progeny cells.

PMID- 22386651
TI  - Somatostatin modulates generation of inspiratory rhythms and determines asphyxia
      survival.
AB  - Breathing and the activity of its generator (the pre-Botzinger complex; pre-BotC)
      are highly regulated functions. Among neuromodulators of breathing, somatostatin
      (SST) is unique: it is synthesized by a subset of glutamatergic pre-BotC neurons,
      but acts as an inhibitory neuromodulator. Moreover, SST regulates breathing both
      in normoxic and in hypoxic conditions. Although it has been implicated in the
      neuromodulation of breathing, neither the locus of SST modulation, nor the
      receptor subtypes involved have been identified. In this study, we aimed to fill
      in these blanks by characterizing the SST-induced regulation of inspiratory
      rhythm generation in vitro and in vivo. We found that both endogenous and
      exogenous SST depress all preBotC-generated rhythms. While SST abolishes sighs,
      it also decreases the frequency and increases the regularity of eupnea and
      gasping. Pharmacological experiments showed that SST modulates inspiratory rhythm
      generation by activating SST receptor type-2, whose mRNA is abundantly expressed
      in the pre-Botzinger complex. In vivo, blockade of SST receptor type-2 reduces
      gasping amplitude and consequently, it precludes auto-resuscitation after
      asphyxia. Based on our findings, we suggest that SST functions as an inhibitory
      neuromodulator released by excitatory respiratory neurons when they become
      overactivated in order to stabilize breathing rhythmicity in normoxic and hypoxic
      conditions.

PMID- 22386652
TI  - Contribution of orodental status to the intensity of orofacial tardive
      dyskinesia: an interdisciplinary and video-based assessment.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a neurological motor complication
      eventually arising in one-third of patients chronically exposed to antipsychotic
      drugs. Some orodental peripheral factors have been reported to influence TD.
      OBJECTIVE: To measure orodental factors such as temporomandibular joint function,
      static occlusal contacts, and denture condition, and attempt correlations with
      orofacial TD intensity. METHODS: In this exploratory cross-sectional pilot study,
      31 subjects between 30 and 75 years of age were divided in two groups displaying
      minimal to mild, or moderate to severe orofacial TD, respectively, and underwent
      a detailed oral, dental, and prosthetic evaluation to capture various aspects of
      oral health compared between the two groups. Blinded video-based TD ratings along
      a validated scale were obtained to compare dentulous and edentulous subjects, and
      contrast TD intensity in complete denture wearers with and without their own
      prostheses. RESULTS: None of the factors examined tightly correlated with
      orofacial TD intensity. However, edentulism was associated with a higher median
      orofacial TD rating compared to the dentulous group (p = 0.001). Further, a
      significant intra-subject difference was observed in the edentulous subjects
      rated with their own complete dentures in place or not (p = 0.028), the dentures
      attenuating the mean orofacial ratings by 21.8 +/- 7.3%. CONCLUSION: Of all
      orodental factors considered, only edentulism and complete denture wearing
      influenced oral TD expression, calling for the close monitoring of the dental
      status in antipsychotic drug-exposed patients to prevent tooth loss. Further
      studies to measure the impact of an adequate prosthodontic rehabilitation in
      edentulous subjects with orofacial TD seem warranted.

PMID- 22386653
TI  - PEDF-derived peptide inhibits corneal angiogenesis by suppressing VEGF
      expression.
AB  - Pigment epithelium-derived factor (PEDF) a glycoprotein that belongs to the
      superfamily of serine protease inhibitors, has been recently shown to be the most
      potent inhibitor of angiogenesis in the mammalian eye. However, which active
      domain of PEDF protein could be involved in its anti-angiogenic properties
      remains unknown. Therefore, in this study, we examined which PEDF-derived
      synthetic peptides could inhibit corneal neovascularization induced by chemical
      cauterization in vivo. Rats treated with topical application of PEDF protein had
      31% less corneal neovascularization at day 7 after the injury than phosphate
      buffered saline (PBS)-treated rats. P5-2 and P5-3 peptides (residues 388-393 and
      394-400 of PEDF protein, respectively) significantly suppressed the corneal
      neovascularization after chemical cauterization at day 7, and its anti-angiogenic
      potential was almost equal to that of full-length PEDF protein. Further, full
      length PEDF protein and P5-3 peptide significantly decreased 8-hydroxy-2'
      deoxyguanosine and vascular endothelial growth factor (VEGF) levels in the
      corneal. Our present study suggests that PEDF-derived synthetic peptide, P5-3
      could inhibit the corneal neovascularization induced by chemical cauterization in
      rats by suppressing VEGF expression via its anti-oxidative properties.

PMID- 22386654
TI  - Effects of polyphenol extract from olive pomace on anoxia-induced endothelial
      dysfunction.
AB  - Anoxia modulates the expression of molecules associated with endothelial
      dysfunction and vascular diseases. Polyphenols have potent antioxidant properties
      due to their ability to modulate genes involved in oxidative tissue damage. In
      this study, we investigated the effect of polyphenol extract from olive pomace
      (PEOP) and its main constituents, Tyrosol and Oleuropein, on endothelial cells
      subjected to anoxia by evaluating the expression of molecules critical for
      endothelial function, proliferation and migration, and the signaling pathway
      involved. EAhy926 human endothelial cells were exposed to anoxic stress in the
      presence or absence of PEOP. Anoxia increased the nitric oxide (NO) level and the
      expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)
      and tumor necrosis factor-alpha (TNFalpha). These effects were prevented by PEOP
      treatment in a dose-dependent manner. Moreover, PEOP prevented the proliferation
      and migration associated with anoxia in EAhy926 cells, down-regulated the levels
      of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type-1 MMP (MT1-MMP) and
      increased tissue MMP inhibitor-1 (TIMP-1) expression. Purified Oleuropein or
      Tyrosol restored to a basal level the anoxia-induced expression of MMP-9 and
      partially of MMP-2. The expression of TNFalpha was reduced by both polyphenols in
      a dose-dependent manner, but more efficiently by Tyrosol. Conversely, Oleuropein
      and Tyrosol had no significant effects on iNOS, COX-2 and TIMP-1 expression when
      used at the concentration found in PEOP. PEOP induced a time-dependent
      phosphorylation of p38 MAPK and ERK1/2 and inhibited anoxia-induced NF-kappaB
      activation. PEOP treatment restores the endothelial functions that are impaired
      by anoxia by regulating the expression of genes involved in proteolysis,
      angiogenesis and inflammation more efficiently than the single purified
      components. Therefore, the combined use of polyphenols, as in PEOP, could
      represent a powerful tool for the treatment and chemoprevention of endothelial
      dysfunction-associated vascular diseases.

PMID- 22386655
TI  - Extracorporeal bypass model of blood circulation for the study of microvascular
      hemodynamics.
AB  - Many studies have been performed to better understand the hemodynamics in
      microvessels, such as arterioles and venules. However, due to the heterogeneous
      features of size, shape, blood-flow velocity, and pulsatility of microvessels,
      conducting a systematic study on these factors has been almost impossible.
      Although in vitro studies have been performed for this purpose, the usefulness of
      in vitro data is limited by the fact that the rheological properties of blood are
      changed as blood is exposed to in vitro environments. The purpose of the present
      study is to investigate the feasibility of a rat extracorporeal bypass model that
      combines in vivo and in vitro models. An arteriovenous shunt loop with a sub
      bypass loop of fluorinated ethylene propylene (FEP) microtube was constructed
      between the jugular vein and femoral artery of a rat. Three pinch valves were
      installed in the main loop. Microscopic images of the blood flow in the FEP tube
      were sequentially captured with a high-speed camera, and the whole velocity field
      information was obtained using a micro-particle image velocimetry technique.
      Experimental results reveal that the velocity fields of the blood flow inside the
      microtube are well measured because the FEP tube is transparent and has nearly
      the same refractive index as water. The flow velocity and the pulsatility index
      of the blood flow in the microtube can be controlled by adjusting the three pinch
      valves installed upstream, midstream, and downstream of the bypass loop. This
      hybrid model that combines in vivo and in vitro models can be useful in studying
      microvascular hemodynamics.

PMID- 22386656
TI  - Craniofacial anomalies amongst births at two hospitals in Nairobi, Kenya.
AB  - The pattern of congenital oral and craniofacial anomalies (CFAs) in the Kenyan
      population remains unknown. The objective of this study was to describe the
      pattern of occurrence of CFAs at two hospitals in Nairobi. A descriptive cross
      sectional study at the Kenyatta National Hospital and Pumwani Maternity Hospital
      was carried out from November 2006 to March 2007. Mothers who delivered at the
      hospitals consented to an interview and physical examination of their babies
      within 48 h of delivery. The anomalies were classified for type and magnitude.
      Data were analysed to determine the association of these anomalies with ages of
      the mothers, gender, weight, birth order, mode of delivery and birth status of
      the babies. During the study period, 7989 babies were born. The CFAs manifested
      in 1.8% of the total births and were more common in female (1.4%) than in male
      (1.0%) live births. 12.8% of stillbirths had CFAs, with lesions manifesting more
      in males (16.7%) than in females (6.9%). The commonest CFA was preauricular sinus
      (4.3/1000) followed by hydrocephalus (1.9/1000) then preauricular tags and cleft
      lip and palate (1.5/1000 and 1.3/1000 total births, respectively).

PMID- 22386657
TI  - Growth inhibitory effects of 3'-nitro-3-phenylamino nor-beta-lapachone against HL
      60: a redox-dependent mechanism.
AB  - In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2
      dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2))
      were investigated and compared with those of its precursor, nor-beta-lapachone
      (nor-beta), with the main goal of proposing a mechanism of antitumor action. The
      results were correlated with those obtained from electrochemical experiments held
      in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the
      presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in
      solution, which provided evidence of a positive interaction with DNA in the case
      of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization
      and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l
      cysteine partially abolished the observed effects related to the QPhNO(2)
      treatment, including those involving apoptosis induction, indicating a partially
      redox-dependent mechanism. These findings point to the potential use of the
      combination of pharmacology and electrochemistry in medicinal chemistry.

PMID- 22386658
TI  - Clinical course of incidental syringomyelia without predisposing pathologies.
AB  - Although the widespread use of MRI has facilitated the diagnosis of subclinical
      syringomyelia, little information has been established regarding its natural
      course. To elucidate the clinical course and treatment strategy of incidental
      syringomyelia without predisposing pathologies, we retrospectively reviewed the
      clinical course of 12 adult patients with incidental syringomyelia. No patients
      had any predisposing pathology, including Chiari malformation or spinal cord
      tumor. Using the medical records and MRI, we analyzed the neurological and
      radiological features of each patient. After a mean of 39.9 months follow-up, no
      patient developed neurological deterioration. Although one patient had
      radiological progression without neurological deterioration, 11 patients (91.7%)
      had no change on MRI. Additionally, all patients experienced a favorable clinical
      course without surgery. These results indicate that, for patients with incidental
      syringomyelia without predisposing pathology, close observation rather than
      surgery can be recommended.

PMID- 22386659
TI  - Prism adaptation alters spatial remapping in healthy individuals: evidence from
      double-step saccades.
AB  - The visual system is able to represent and integrate large amounts of information
      as we move our gaze across a scene. This process, called spatial remapping,
      enables the construction of a stable representation of our visual environment
      despite constantly changing retinal images. Converging evidence implicates the
      parietal lobes in this process, with the right hemisphere having a dominant role.
      Indeed, lesions to the right parietal lobe (e.g., leading to hemispatial neglect)
      frequently result in deficits in spatial remapping. Research has demonstrated
      that recalibrating visual, proprioceptive and motor reference frames using prism
      adaptation ameliorates neglect symptoms and induces neglect-like performance in
      healthy people - one example of the capacity for rapid neural plasticity in
      response to new sensory demands. Because of the influence of prism adaptation on
      parietal functions, the present research investigates whether prism adaptation
      alters spatial remapping in healthy individuals. To this end twenty-eight
      undergraduates completed blocks of a double-step saccade (DSS) task after sham
      adaptation and adaptation to leftward- or rightward-shifting prisms. The results
      were consistent with an impairment in spatial remapping for left visual field
      targets following adaptation to leftward-shifting prisms. These results suggest
      that temporarily realigning spatial representations using sensory-motor
      adaptation alters right-hemisphere remapping processes in healthy individuals.
      The implications for the possible mechanisms of the amelioration of hemispatial
      neglect after prism adaptation are discussed.

PMID- 22386660
TI  - CD133+CD34+ and CD133+CD38+ blood progenitor cells as predictors of platelet
      engraftment in patients undergoing autologous peripheral blood stem cell
      transplantation.
AB  - BACKGROUND: Hematopoietic stem cells (HSC) have been characterized by CD34+
      expression and an adequate dose of CD34+ cells is associated with a complete
      engraftment. CD133 is a more specific marker of HSC. MATERIALS AND METHODS: We
      studied the relationship between graft content of CD34+, CD133+, and CD38+ cells
      and trilineage engraftment after autologous stem cell transplantation in patients
      with different hematological disorders. Blood samples were obtained before and
      after mobilization with recombinant granulocyte-colony stimulating factor (G-CSF,
      16 MUg/kg), from apheresis collections, and after transplantation. RESULTS: Cell
      subsets were quantified by flow cytometry, and the dose of each population
      infused was correlated with success of engraftment. G-CSF induced mobilization of
      CD133+CD38+ cells (12.6-fold) and CD133+CD34+ cells (14.7-fold). A correlation
      was observed between the infused dose of CD133+CD34+ and CD133+CD38+ cells and
      platelet engraftment. CONCLUSION: CD133+CD34+ and CD133+CD38+ cells were
      mobilized with G-CSF and these cell subsets were correlated with platelet
      engraftment.

PMID- 22386661
TI  - Determination of plutonium isotopes in seawater reference materials using isotope
      dilution ICP-MS.
AB  - We analyzed the activities of (239)Pu, (240)Pu, (239+240)Pu, (241)Pu, the ratio
      of number of atoms (atom ratio) for (240)Pu/(239)Pu, and the activity ratio of
      (241)Pu/(239+240)Pu in seawater reference materials, IAEA-443 and IAEA-381, using
      a highly sensitive isotope dilution sector field inductively coupled plasma mass
      spectrometry method. With a mean chemical yield of 65% determined with (242)Pu as
      a tracer, we found that the experimentally established values in IAEA-443 for
      (239)Pu, (240)Pu, (241)Pu and (239+240)Pu activities are almost the same as those
      in IAEA-381. Regarding the (239+240)Pu activity, we provided the most precise and
      accurate result among the twelve laboratories, which participated in the
      interlaboratory comparison. In addition, for the (240)Pu/(239)Pu atom ratio, our
      results for IAEA-381 (0.2315+/-0.0008) and IAEA-443 (0.2325+/-0.0008) are in good
      agreement with the IAEA information value (0.229+/-0.006), but have much smaller
      uncertainty. Since the new seawater reference material, IAEA-443, is commercially
      available, it can be used not only for method validation for seawater plutonium
      isotope ratio and activity analysis, but also for more general use as a plutonium
      isotope standard for mass discrimination correction for other environmental
      samples.

PMID- 22386662
TI  - Water equivalence of some plastic-water phantom materials for clinical proton
      beam dosimetry.
AB  - Plastic-water phantom materials are not exactly water equivalent since they have
      a different elemental composition and different interaction cross sections for
      protons than water. Several studies of the water equivalence of plastic-water
      phantom materials have been reported for photon and electron beams, but none for
      clinical proton beams. In proton beams, the difference between non-elastic
      nuclear interactions in plastic-water phantom materials compared to those in
      water should be considered. In this work, the water equivalence of Plastic
      Water(r) (PW)1, Plastic Water(r) Diagnostic Therapy (PWDT)1 and solid water
      (WT1)2 phantoms was studied for clinical proton energies of 60 MeV and 200 MeV.
      This was done by evaluating the fluence correction factor at equivalent depths;
      first with respect to water and then with respect to graphite by experiment and
      Monte Carlo (MC) simulations using FLUKA. MC simulations showed that the fluence
      correction with respect to water was less than 0.5% up to the entire penetration
      depth of the protons at 60 MeV and less than 1% at 200 MeV up to 20 cm depth for
      PWDT, PW and WT1. With respect to graphite the fluence correction was about 0.5%
      for 60 MeV and about 4% for 200 MeV. The experimental results for modulated and
      un-modulated 60 MeV proton beams showed good agreement with the MC simulated
      fluence correction factors with respect to graphite deviating less than 1% from
      unity for the three plastic-water phantoms.

PMID- 22386663
TI  - Using tracer methods and experimental design approach for examination of
      hydrodynamic conditions in membrane separation modules.
AB  - The possibility of application of fluorescein and radioactive 99mTc as tracers
      for determination of residence time distribution of liquid phase and for
      diagnosing hydrodynamic conditions in apparatuses for membrane separation was
      studied. Two different ultrafiltration systems with diverse arrangement of liquid
      flow: the apparatus with helical flow generated by the movable element (inner
      cylinder) and the tubular module with cross flow filtration, were tested by the
      RTD technique. The tracer studies were supplemented with modelling. The optimal
      conditions enabling to handle the plug flow-like structure in the helical
      apparatus were determined. The minimum of dimensionless variance (vard) was
      obtained at P=0.765 bar, Q(R)=121.88 l/h and Omega=2887.5 rpm. In spite of higher
      linear velocities attained in the tubular cross-flow module, the flow structure
      in the helical apparatus was more similar to the ideal plug flow pattern that was
      demonstrated by higher Peclet numbers and lower values of the dimensionless
      variance. Application of movable part and Couette-Taylor flow in the membrane
      apparatus may balance the advantages coming from high flow rates applied in cross
      flow filtration systems minimising formation of the deposit on the membrane
      surface and reducing membrane fouling.

PMID- 22386664
TI  - Determination of intracellular pH using sensitive, clickable fluorescent probes.
AB  - We synthesized and evaluated a series of acidic fluorescent pH probes exhibiting
      robust pH dependence, high sensitivity and photostability, and excellent cell
      membrane permeability. Titration analyses indicated that probe 3 could increase
      its fluorescence intensity 800-fold between pH 8.0 and 4.1. Additionally, its
      pK(a) value is optimal for intracellular probing of acidic organelles.
      Fluorescent imaging of HepG2 and Hela cells further revealed that probe 3
      demonstrates outstanding capacity for monitoring of intracellular [H(+)] levels.
      The easily accessible terminal alkyne/azido function groups of these probes offer
      the possibility of rapidly constructing sensor molecule libraries using 'click'
      chemistry.

PMID- 22386665
TI  - 3-Phenyl-5-isothiazole carboxamides with potent mGluR1 antagonist activity.
AB  - The disclosed 3-phenyl-5-isothiazole carboxamides are potent allosteric
      antagonists of mGluR1 with generally good selectivity relative to the related
      group 1 receptor mGluR5. Pharmacokinetic properties of a member of this series
      (1R,2R)-N-(3-(4-methoxyphenyl)-4-methylisothiazol-5-yl)-2
      methylcyclopropanecarboxamide (14) are good, showing acceptable plasma and brain
      exposure after oral dosing. Oral administration of isothiazole 14 gave robust
      activity in the formalin model of persistent pain which correlated with CNS
      receptor occupancy.

PMID- 22386666
TI  - Accidental latissimus dorsi flap pedicle avulsion during immediate breast
      reconstruction: salvage by conversion to free flap.
AB  - Pedicle damage is a rare complication of latissimus dorsi (LD) flap breast
      reconstruction. We report a case of accidental avulsion of the vascular pedicle
      of a totally autologous (extended) LD flap during immediate breast reconstruction
      in a patient who had previously undergone contralateral breast reconstruction
      with a pedicled TRAM flap based on the opposite superior epigastric vessels. The
      intra-operative strategy to salvage the avulsed LD flap by conversion to a free
      flap while not compromising the contralateral breast reconstruction is discussed.

PMID- 22386667
TI  - Spontaneous mediastinal hematoma as an initial manifestation of ectopic
      parathyroid cystadenoma.

PMID- 22386668
TI  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with multiple
      synchronous carcinoid tumors.
AB  - The spectrum of pulmonary neuroendocrine cell proliferation ranges from reactive
      hyperplasia to small cell carcinoma and includes diffuse idiopathic pulmonary
      neuroendocrine cell hyperplasia. A case is reported and features of this disease
      are described according to the published evidence. The entity was first included
      in the WHO classification of tumors in 1999 and is considered a preneoplastic
      condition for carcinoid tumors. Patients generally report slowly progressive
      dyspnea and cough, and have airflow obstruction, multiple pulmonary nodules
      and/or radiological signs of air trapping, although asymptomatic cases with
      normal pulmonary function have been described. Histologically, it is
      characterized by neuroendocrine cell proliferation in the airway epithelium, in
      most cases beyond the basal membrane forming tumorlets and carcinoid tumors that
      are frequently multiple. The prognosis is favorable in most cases.

PMID- 22386669
TI  - External validation of the recommendations of the multidisciplinary consensus
      about inhaled therapies.
AB  - The understanding of physicians and the skill of patients in the use of inhalers
      continues to be inadequate. OBJECTIVE: The external validation, by an expert
      panel, of practical clinical recommendations that had been developed in order to
      improve the knowledge and understanding of correct inhaled therapy use. METHODS:
      After a bibliographic review about inhaled therapies, 40 clinical recommendations
      were proposed. A two-round modified Delphi consensus was used to compare the
      opinions of a panel of 59 experts about the recommendations, which were grouped
      into 8 areas: general aspects (4), inhaled drugs (9), pressurized metered-dose
      and spacer inhalers (6), powder inhalers (4), nebulizers (3), devices for
      mechanical ventilation (3), inhalers for children (5) and issues related with
      compliance and education (6). RESULTS: After the first round of the consensus
      panel, 35 of the 40 recommendations analyzed were accepted. At the end of round
      2, agreement was reached in 39 (97.5%). In 8 (20%), the consensus was unanimous
      (100%). Item 14 was deleted from the recommendations as consensus was not
      reached. CONCLUSIONS: The external validation by experts in inhaled therapy found
      a high level of agreement with the clinical recommendations proposed. This
      consensus provides a tool that could contribute to the improved use of inhalers
      in our country in the future.

PMID- 22386670
TI  - Dissemination of pHK01-like incompatibility group IncFII plasmids encoding CTX-M
      14 in Escherichia coli from human and animal sources.
AB  - Few studies have compared CTX-M encoding plasmids identified in different
      ecological sources. This study aimed to analyze and compare the molecular
      epidemiology of plasmids encoding CTX-M-14 among strains from humans and animals.
      The CTX-M-14 encoding plasmids in 160 Escherichia coli isolates from animal
      faecal (14 pigs, 16 chickens, 12 cats, 8 cattle, 5 dogs and 3 rodents), human
      faecal (45 adults and 20 children) and human urine (37 adults) sources in 2002
      2010 were characterized by molecular methods. The replicon types of the CTX-M-14
      encoding plasmids were IncFII (n=61), I1-Igamma (n=24), other F types (n=23), B/O
      (n=10), K (n=6), N (n=3), A/C (n=1), HI1 (n=1), HI2 (n=1) and nontypeable (n=30).
      The genetic environment, ISEcp1 -bla(CTX-M-14) - IS903 was found in 89.7%
      (52/58), 87.7% (57/65) and 86.5% (32/37) of the animal faecal, human faecal and
      human urine isolates, respectively. Subtyping of the 61 IncFII incompatibility
      group plasmids by replicon sequence typing, plasmid PCR-restriction fragment
      length polymorphism and marker genes (yac, malB, eitA/eitC and parB/A) profiles
      showed that 31% (18/58), 30.6% (20/65) and 37.8% (14/37) of the plasmids
      originating from animal faecal, human faecal and human urine isolates,
      respectively, were pHK01-like. These 52 pHK01-like plasmids originated from
      diverse human (20 faecal isolates from 2002, 2007 to 2008, 14 urinary isolates
      from 2004) and animal (all faecal, 1 cattle, 1 chicken, 5 pigs, 9 cats, 1 dog, 1
      rodent from 2008 to 2010) sources. In conclusion, this study highlights the
      importance of the IncFII group, pHK01-like plasmids in the dissemination of CTX-M
      14 among isolates from diverse sources.

PMID- 22386671
TI  - Occurrence of MRSA in air and housing environment of pig barns.
AB  - A high prevalence of MRSA among farm animals, especially pigs, has been observed
      for some time. However, knowledge on transmission routes of MRSA in livestock
      production is still scarce. Therefore, the aim of this study was to determine the
      occurrence of MRSA in pig house air as well as in samples from pigs and their
      housing environment in 27 MRSA positive pig barns of different sizes and
      production types. In 85.2% of all barns MRSA was detected in the animal house
      air. Impingement turned out to be a more sensitive sampling technique than
      filtration. Other environmental samples such as boot swabs or faeces showed
      prevalences of MRSA from 55.6% to 85.2% at sample level. The level of MRSA was
      88.3% for pooled and 82.1% for single nasal swabs, in skin swabs the one was
      87.7%, the others was 78.7%. Spa typing of isolates from air and nasal swabs
      showed predominantly spa types t011 and t034. MRSA prevalences in pigs as well as
      in various environmental samples were significantly higher in fattening farms
      than in breeding farms. This study provides good reference that there could be an
      airborne transmission of MRSA within pig herds indicating a potential
      contamination of the environment of barns.

PMID- 22386672
TI  - In vivo gene expression in Mannheimia haemolytica A1 during a time-course trial
      in the bovine host.
AB  - The objective of this study is to examine the expression of Mannheimia
      haemolytica genes over time during the early stage of infection. In addition,
      gene expression at different sites of infection in the bovine host was examined.
      A time-course experiment was designed to collect pharyngeal swabs and lung
      washings from the same animals over two time points. Six calves were
      experimentally challenged with M. haemolytica A1; pharyngeal swabs were collected
      from all animals 5h post infection. Three calves were euthanized at 6h;
      pharyngeal swabs were collected from the remaining 3 calves at 12h and the calves
      were euthanized. Lung washings were recovered from all animals at necropsy. Total
      RNA was prepared from the pharyngeal swabs and lung washings and primers for
      eight well characterized virulence-associated genes were used in qRT-PCR to
      examine mRNA levels. The expression of key virulence genes such as lktA, gcp and
      tbpB was higher in vivo compared to in vitro with the highest changes observed
      from 6 to 12h. The expression of lktA and gapA increased while expression of
      fbpA, gs60, nmaA and tbpB was found to decreased over time in the 6h period. Gene
      expression profiles in the lungs versus the pharynx also differed, with most
      genes (fbpA, tbpB, nmaA, gs60, lktA and narP) showing higher expressing in lung
      washings. This is the first study to follow gene expression by M. haemolytica in
      the same animal over time during an infection.

PMID- 22386673
TI  - Rapid MALDI-TOF mass spectrometry identification of Leptospira organisms.
AB  - Leptospirosis is a worldwide deadly zoonotic disease. Accurate identification of
      the causative Leptospira spp. spirochetes ascertains the pathogenic status of the
      isolates, identifies potential source of infection and recognises outbreaks.
      Species identification is currently based on technically demanding, time and
      resources consuming serological and molecular methods. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) recently
      emerged as a first-line method for the accurate identification of bacteria, yet
      no data issued for Leptospira spp. We investigated the potential of MALDI-TOF-MS
      for the rapid identification of Leptospira isolates. Starting from a
      10(5)organisms/mL suspension, MALDI-TOF-MS yielded an unique protein profile for
      each one of 19 Leptospira species reference isolates with a 100% reproducibility
      over 12 repeats, allowing to create a Leptopsira database. MALDI-TOF-MS further
      accurately identified 20/21 additional reference isolates representative of
      various serogroups at the species level as Leptospira interrogans (n=12),
      Leptospira kirschneri (n=5), Leptospira borgpetersenii (n=3), Leptospira noguchii
      (n=1) with identification score value of 2-2.5. Furthermore, six clinical
      isolates previously identified by rpoB sequencing, were correctly identified by
      MALDI-TOF-MS as L. interrogans (n=5) and L. borgpetersenii (n=1) with
      identification score value of 2-2.6. Identification was achieved in 40 min
      starting from the Leptospira suspension. MALDI-TOF-MS could complement
      serological and sequencing-based methods for the first line, rapid identification
      of Leptospira isolates in the clinical microbiology laboratory.

PMID- 22386674
TI  - EcPV-2 is transcriptionally active in equine SCC but only rarely detectable in
      swabs and semen from healthy horses.
AB  - Squamous cell carcinomas (SCC) are malignant tumours arising from keratinocytes.
      In horses, there is increasing evidence for Equus caballus papillomavirus type 2
      (EcPV-2) being causally involved in SCC development. However, only little is
      known regarding intralesional transcription of the virus, and sparse information
      on the incidence of EcPV-2 infection in healthy equids is available so far. Using
      RT-PCR, total mRNA from 8 EcPV-2 DNA-positive and 1 EcPV-2 negative SCC/SCC
      precursor lesions was screened for the presence of EcPV-2 E6 and E1 transcripts.
      Using PCR, we tested 193 sample specimens (30 ocular swabs, 94 genital swabs, 54
      semen and 15 milk samples) from a total of 161 apparently healthy horses for the
      presence of EcPV-2 genes E7 and E6 or E2. Positive results were confirmed by
      repeating the PCR reactions, and by amplicon sequencing. E6 mRNA was detectable
      in 8/8 EcPV-2 DNA-positive lesions, whereas only 3/8 scored positive for E1 mRNA.
      EcPV-2 PCR scored positive for DNA from 1/30 ocular swabs, 4/94 genital swabs,
      0/54 semen and 0/15 milk samples, thus resulting in an overall detection rate of
      5/193, i.e. 2.6%. The demonstrated presence of viral mRNA in all EcPV-2 DNA
      positive lesions is suggestive for an active pathogenic role of the virus in SCC
      development. This finding and the low incidence of EcPV-2 DNA in healthy equids
      further strengthen the concept of an aetiologic association of EcPV-2 with equine
      SCC disease.

PMID- 22386675
TI  - An up-date on the differentiation of Brachyspira species from pigs with nox-PCR
      based restriction fragment length polymorphism.
AB  - Different Brachyspira (B.) species colonize the porcine intestinal tract, some of
      which are pathogens of significant clinical and economic importance. In 2002 we
      published a novel molecular method for differentiation of Brachyspira species
      from pigs based on the amplification of the nox-gene and the generation of
      species-specific restriction patterns (nox-RFLP) using the enzymes BfmI and DpnII
      (Rohde et al., 2002). We applied this method for identification in addition to
      biochemical testing in doubtful cases until 2008. Since 2009 we have used it as
      the first line method of identification. The current study documents the results
      of examining 2050 Brachyspira isolates collected from January 2009 to December
      2011. In addition to identifying isolates with previously described patterns,
      four novel restriction fragment length patterns were observed, and isolates with
      these patterns could be assigned to the species B. intermedia and the B.
      innocens/murdochii complex on the basis of their phenotypic properties and by nox
      sequence analysis. In 2007 a potentially new Brachyspira species, "B. suanatina",
      was described in Swedish pigs (Rasback et al., 2007). From the published nox-gene
      sequence it could be expected that this Brachypira species should show a new
      restriction pattern making nox-RFLP a suitable technique for identification of
      "B. suanatina". In this study the new restriction fragment length pattern could
      be demonstrated in one of the strains described by Rasback et al. (AN4859/03).
      Nevertheless, no isolates with this new pattern corresponding to "B. suanatina"
      were identified amongst the 2050 Brachyspira isolates examined from northern
      Germany.

PMID- 22386676
TI  - Cerebral malaria: what is known and what is on research.
AB  - Malaria is still the world's major important parasitic disease and is responsible
      for the death of more people than any other communicable disease except
      tuberculosis. A major change in recent years has been the recognition that severe
      malaria, predominantly caused by Plasmodium falciparum, is a complex multi-system
      disorder presenting with a range of clinical features. Some surviving patients
      have an increased risk of neurological and cognitive deficits, behavioural
      difficulties and epilepsy, making cerebral malaria a leading cause of childhood
      neurodisability in the malaria transmission area. It is unclear how an
      intravascular parasite causes such brain injury. Understanding of these
      mechanisms is important to develop appropriate neuroprotective interventions.
      However, due to the high specificity of P. falciparum to the human host and to
      the fact that clinical studies in human are not always feasible, our knowledge
      about this syndrome mainly comes from autopsy studies which can only give us a
      limited view of this deadly syndrome. Efforts developed by the scientific
      community have shown that development of severe malaria probably results from a
      combination of parasite-specific factors such as adhesion and sequestration to
      the vascular endothelium, the release of bioactive molecules, together with host
      inflammatory responses and metabolic acidosis. Recent studies have shown that
      endothelial cells could play a central role in the onset of the severe malaria.
      Indeed, adhesion of parasitized erythrocytes to these cells could drive their
      activation, which could participate in the trigger of an immune response and
      haemostatic derangements. Moreover, death of endothelial cells could be at the
      origin of the blood-lung/brain barrier breakdown. Despite the efforts to find new
      mechanisms, which explain the physiopathology of severe malaria, research
      progress is slowed down by the lack of experimental models, which reproduce this
      complex multi-system disorder. In absence of a vaccine so far, the rapid
      diagnosis of the disease, an efficient treatment, a correct management and
      nursing care are the only weapons to control mortality due to P. falciparum. It
      is important to note that in the future, the treatment of severe malaria may
      involve adjuvant treatments in addition to a potent antimalarial drug. In the
      present review, we summarize both what is known and practically useful for a
      physician, and the most promising and current topics of research.

PMID- 22386677
TI  - Horses, hormones and habits.

PMID- 22386678
TI  - Impact of non-invasive fetal RhD genotyping on management costs of rhesus-D
      negative patients: results of a French pilot study.
AB  - OBJECTIVES: Fetal rhesus D (RhD) status determination using circulating cell-free
      fetal DNA from maternal plasma or serum is now recognized in Europe as a reliable
      and useful tool. A few countries are presently using this test in their
      management policy of rhesus D negative patients. The objective of this study is
      to evaluate the impact of this test on the costs of managing RhD-negative
      pregnant women, whether or not they are allo-immunized. STUDY DESIGN: A
      prospective follow-up of rhesus D negative women during their pregnancy was
      performed in three French obstetric departments. Non-invasive fetal RhD
      genotyping was performed in the first trimester and pregnancies were followed The
      costs of all procedures (biological tests and medication) associated with patient
      management in relation to their RhD-negative status were calculated according to
      different management options. RESULTS: A comprehensive follow-up, including
      medical and biological monitoring, was obtained for 99 of the 101 patients
      included in the study. Patients were separated into two groups: the "Adverse
      Event" group (AE, n=23) for which a potentially sensitizing event occurred and
      the "No Adverse Event" group (NAE, n=76). Fetal RhD status was accurately
      determined in all cases. The mean cost per patient was estimated at 237? (range:
      115-644) with differences observed depending on the group, notably 331? (range:
      236-644) for the AE group and 208? (range: 115-366) for the NAE group. Various
      cost simulations were performed according to various policies of allo
      immunization antenatal prophylaxis. Variations ranged from +36.2% to +105.3%.
      CONCLUSION: This study demonstrates that fetal RhD genotyping early during
      pregnancy is not an effective cost-reduction strategy whether or not antenatal
      prophylaxis is given. The economic issues could, however, be overcome by the fact
      that there is a major clinical benefit to offering the test systematically to all
      RhD-negative pregnant women while avoiding unnecessary testing and immunoglobulin
      injections.

PMID- 22386679
TI  - Cost-minimisation analysis of endometrial thermal ablation in a day case or
      outpatient setting under different anaesthesia regimens.
AB  - OBJECTIVE: To evaluate the cost difference between a daycase endometrial thermal
      ablation performed under general anaesthesia and an outpatient endometrial
      ablation using local anaesthetic. STUDY DESIGN: Calculations using real reported
      resource use in 20 daycase procedures and 16 outpatient procedures. RESULTS: The
      costs were 1865 euros for daycase procedure versus 1065 euros for outpatient
      procedure. CONCLUSION: The cost of endometrial thermal ablation can be
      considerably minimised by taking the procedure out of the theatre and performing
      it under local anaesthetic instead of general anaesthesia. This setting makes
      endometrial thermal ablation cost-effective.

PMID- 22386680
TI  - [Oriental sore due to Leishmania infantum (L. chagasi)].

PMID- 22386681
TI  - [Family medicine and hospital tutors in regards to changes in specialized
      training].

PMID- 22386682
TI  - Thromboembolic disease: prophylaxis in the elderly?

PMID- 22386683
TI  - Human health risks of Pb and As exposure via consumption of home garden
      vegetables and incidental soil and dust ingestion: a probabilistic screening
      tool.
AB  - The consumption of home grown vegetables may represent a significant exposure
      pathway for arsenic (As) and lead (Pb) relative to direct incidental ingestion of
      soil, thus a probabilistic screening tool for estimating these exposures was
      developed using regression models relating co-located soil and home garden (HG)
      vegetable concentrations of Pb and As established from multiple independent
      studies and 2-dimensional Monte Carlo analyses. For high-quantity consumers of HG
      vegetables (i.e., the upper 95th percentile of consumers in the general
      population), the HG consumption pathway can be as significant as incidental soil
      and dust ingestion for inorganic As and, therefore, should be considered when
      developing generic health-based soil criteria in residential settings. Predicted
      Pb Hazard Quotient (HQ) estimates among young children resulting from HG
      consumption were 4- to 10-fold lower than exposures resulting from direct
      incidental soil and dust ingestion. The difference in soil/dust ingestion rates
      used to characterize young children (the 95th percentile of 202 mg/d) versus a
      lifetime residential receptor (the 95th percentile of 30 mg/d) was a primary
      factor contributing to the relative differences observed between HQ and
      incremental lifetime cancer risk (ILCR) resulting from these two exposure
      pathways for lead Pb and inorganic arsenic As, respectively.

PMID- 22386684
TI  - Segregation of calcium signalling mechanisms in magnocellular neurones and
      terminals.
AB  - Every cell or neuronal type utilizes its own specific organization of its Ca(2+)
      homeostasis depending on its specific function and its physiological needs. The
      magnocellular neurones, with their somata situated in the supraoptic and
      paraventricular nuclei of the hypothalamus and their nerve terminals populating
      the posterior hypophysis (neural lobe) are a typical and classical example of a
      neuroendocrine system, and an important experimental model for attempting to
      understand the characteristics of the neuronal organization of Ca(2+)
      homeostasis. The magnocellular neurones synthesize, in a cell specific manner,
      two neurohormones: arginine-vasopressin (AVP) and oxytocin (OT), which can be
      released, in a strict Ca(2+)-dependent manner, both at the axonal terminals, in
      the neural lobe, and at the somatodendritic level. The two types of neurones show
      also distinct type of bioelectrical activity, associated with specific secretory
      patterns. In these neurones, the Ca(2+) homeostatic pathways such as the
      Na(+)/Ca(2+) exchanger (NCX), the endoplasmic reticulum (ER) Ca(2+) pump, the
      plasmalemmal Ca(2+) pump (PMCA) and the mitochondria are acting in a
      complementary fashion in clearing Ca(2+) loads that follow neuronal stimulation.
      The somatodendritic AVP and OT release closely correlates with intracellular
      Ca(2+) dynamics. More importantly, the ER Ca(2+) stores play a major role in
      Ca(2+) homeostatic mechanism in identified OT neurones. The balance between the
      Ca(2+) homeostatic systems that are in the supraoptic neurones differ from those
      active in the terminals, in which mainly Ca(2+) extrusion through the Ca(2+) pump
      in the plasma membrane and uptake by mitochondria are active. In both AVP and OT
      nerve terminals, no functional ER Ca(2+) stores can be evidenced experimentally.
      We conclude that the physiological significance of the complexity of Ca(2+)
      homeostatic mechanisms in the somatodendritic region of supraoptic neurones and
      their terminals can be multifaceted, attributable, in major part, to their
      specialized electrical activity and Ca(2+)-dependent neurohormone release.

PMID- 22386685
TI  - Commentary on, 'Internal reliability of measures of substance-related cognitive
      bias'.
AB  - A recent paper published in Drug and alcohol dependence (Ataya et al., 2012) is
      the first systematic attempt to establish the internal reliability of measures of
      substance-related attentional bias, and it makes an important and long overdue
      contribution to this topic. The authors reported that the reliability of
      attentional bias indices derived from the visual probe task was very poor, and
      while the attentional bias index from the Stroop was a little better, it fell
      some way short of being acceptable, as alpha>0.70 in only two of six studies in
      which the task was used. In this commentary, we speculate on some of the factors
      that might have contributed to the poor reliability of the tasks, and how task
      reliability might be improved in future studies.

PMID- 22386686
TI  - Alcohol use and abuse among rural Zimbabwean adults: a test of a community-level
      intervention.
AB  - BACKGROUND: Understanding what factors contribute to alcohol abuse in resource
      poor countries is important given its adverse health consequences. Past research
      shows that social peers influence substance abuse, suggesting that the social
      environment may be an effective target for reducing alcohol abuse across a
      population. This study investigates the determinants of alcohol use and abuse in
      rural Zimbabwe and tests a community popular opinion leader (CPOL) community
      based intervention partly directed at reducing alcohol abuse. METHODS: Tests were
      conducted on the impact of the CPOL intervention on alcohol use patterns across
      communities in rural Zimbabwe over three waves from 2003 to 2007, including
      community- and individual-level tests using data based on in-person interviews of
      adult men and women (ages 18-30; N=5543). Data were analyzed using paired-sample
      t-tests, as well as logistic and ordinary least-squares regression with random
      effects. RESULTS: Higher drinking (any use, more frequent use, greater quantity,
      and/or frequent drunkenness) was generally associated with being male, older, not
      married, more highly educated, of Shona ethnicity, away from home frequently,
      employed, having no religious affiliation, or living in areas with a higher crude
      death rate or lower population density. Over the study period, significant
      declines in alcohol use and abuse were found in intervention and control sites at
      relatively equal levels. CONCLUSIONS: Although no support was found for the
      effectiveness of the CPOL study in reducing alcohol abuse, Zimbabwe is similar to
      other countries in the impact of socio-demographic and cultural factors on
      alcohol use and abuse.

PMID- 22386687
TI  - Returning to work after a stroke: a retrospective study at the Physical and
      Rehabilitation Medicine Center La Tour de Gassies.
AB  - OBJECTIVE: To study work re-entry by patients having suffered a stroke at least 3
      years previously. PATIENTS AND METHODS: This was a retrospective survey in which
      a questionnaire was administered to all patients admitted after a first stroke to
      the "La Tour de Gassies" Centre for Physical and Rehabilitation Medicine (CPRM)
      in France between January 2005 and June 2007 and who were in work at the time of
      the incident. RESULTS: Fifty-six of the 72 included patients (78%) completed and
      returned the survey questionnaire. The mean age at the time of the stroke was
      48.3+/-10.1. Eighteen (32.1%) of the 56 patients returned to work after their
      stroke (mean post-stroke time interval: 19.2+/-13.4 months). Negative prognostic
      factors for a return to work were living alone, the presence of severe functional
      impairment and the presence of speech disorders. Positive prognostic factors
      included specific, professional support and early involvement of the occupational
      physician. Patients who resumed driving were more likely to return to work and
      there was a positive correlation between the time to work re-entry and the time
      to resumption of driving. CONCLUSION: Close cooperation between occupational
      health services and CPRM appears to be necessary to speed the return to work by
      stroke patients.

PMID- 22386689
TI  - Heat shock protein 72 inhibits c-Jun N-terminal kinase 3 signaling pathway via
      Akt1 during cerebral ischemia.
AB  - Although recent researches show that Heat Shock Protein 72 (HSP72) plays an
      important role in neuronal survival, little knowledge is known about the precise
      mechanisms during cerebral ischemia/reperfusion (I/R). Our present study
      investigated the neuroprotective mechanisms of HSP72 against ischemic brain
      injury induced by cerebral I/R. Mild heat shock pretreatment was employed to
      induce the overexpression of HSP72 by immersing rats into the water bath at 42
      degrees C for 20 min before cerebral I/R. HSP72 antisense oligodeoxynucleotides
      (ODNs) were used to inhibit HSP72 expression by intracerebroventricular infusion
      once per day for 3 days before cerebral I/R animal model was induced by four
      vessel occlusion for 15 min transient ischemia and then reperfused for various
      time in Sprague-Dawley rats. Immunoprecipitation and immunoblotting were used to
      detect the expression of the related proteins. HE-staining and TUNEL-staining
      were carried out to examine the neuronal death of hippocampal CA1 region. Results
      showed that mild heat shock could increase the phosphorylation of protein kinase
      B (Akt), inhibit the assembly of MLK3-MKK7-JNK3 signaling module, diminish the
      phosphorylation of JNK3 and c-Jun, and decrease the activation of caspase-3.
      Furthermore, mild heat shock could significantly protect neurons against cerebral
      I/R. Whereas, all of the aforementioned effects of mild heat shock were reversed
      by HSP72 antisense ODNs. In summary, our results imply that Akt1 activation is
      involved in the neuroprotection of HSP72 against ischemic brain injury via
      suppressing JNK3 signaling pathway and provide a new experimental foundation for
      stroke therapy.

PMID- 22386690
TI  - The role of omega-3 polyunsaturated fatty acids in reproduction of sheep and
      cattle.
AB  - The positive effects of fat and energy supplementation on improvements in
      reproduction are well documented. However, the specific effects of omega-3
      polyunsaturated fatty acids (n-3) on reproductive success in ruminants have not
      been examined in detail. While the link between n-3 and markers associated with
      reproduction, in particular, prostaglandin F(2alpha) (PGF(2alpha)) and the link
      between PGF(2alpha) and reproductive outcomes are well established, evidence of a
      direct effect of high n-3 diets on measurable reproductive outcomes in ruminants
      is lacking. Therefore, the aim of the current review was to examine the effect of
      n-3 on a number of reproductive markers and measurable outcomes in sheep and
      cattle. There is strong evidence linking consumption of diets high in n-3 with
      reduced circulating peripheral inflammatory markers such as PGF(2alpha).
      Inflammatory eicosanoids including PGF(2alpha), in particular, can significantly
      affect reproduction outcomes such as the onset of oestrus, embryo survival and
      parturition. While there is also evidence linking n-3 supplementation with longer
      time to oestrus and parturition associated with reduced PGF(2alpha), the effects
      of n-3 on other measurable outcomes of reproductive success, such as pregnancy
      rate, embryo survival and intergenerational effects on the health and production
      of offspring are largely unknown. Similarly, the effects of diets high in n-3 or
      n-6 polyunsaturated fatty acids on male fertility are also unknown.

PMID- 22386691
TI  - Lack of association between the CXCL12 rs501120 polymorphism and cardiovascular
      disease in Spanish patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated
      atherosclerosis. CXCL12 is a strong chemotactic signal for lymphocytes. Because
      previous genome-wide association studies demonstrated an association between
      CXCL12 rs501120 and coronary artery disease, in the present study we assessed the
      potential association of this polymorphism with the risk of cardiovascular (CV)
      disease in 1,321 Spanish patients with RA. A subgroup of patients without CV
      events was also studied to determine the presence of subclinical atherosclerosis
      by ultrasonography (brachial flow-mediated endothelium-dependent vasodilatation
      and carotid intima-media wall thickness). However, no significant differences in
      genotypic and allelic frequencies between RA patients with and without CV events
      were observed, as was also the case when values of surrogate markers of
      atherosclerosis were assessed according to CXCL12 rs501120 genotype frequencies.
      In conclusion, our results do not confirm an association of the CXCL12 rs501120
      polymorphism with atherosclerosis or with CV disease in RA.

PMID- 22386692
TI  - Immune responses to self-antigens in asthma patients: clinical and
      immunopathological implications.
AB  - Asthma leads to chronic airway inflammation that shares pathological features of
      chronic rejection after lung transplantation. Due to the significant role of
      autoimmunity in chronic rejection, we hypothesized that immunity to self-antigens
      may also be present in asthma. The goal was to define immune responses to self
      antigens in patients with asthma. Blood and clinical data were collected from 99
      asthmatics and 60 controls. Serum was analyzed for antibodies (Abs) to collagen V
      (ColV) by enzyme-linked immunosorbent assay and correlated with disease severity.
      Asthmatics' sera were tested in a human protein array to determine immune
      responses to other self-antigens. Asthmatics had higher concentrations of Abs to
      ColV (predominantly immunoglobulin G isotype) compared with controls (p < 0.01).
      These Abs correlated with severe asthma (p < 0.01) and corticosteroid use (p =
      0.032). Additionally, Abs to novel self-antigens epidermal group factor receptor
      (EGFr), activin A type 1 receptor, and alpha-catenin were detected in asthmatics.
      We conclude that Abs to self-antigens (ColV, EGFr, activin A type 1 receptor, and
      alpha-catenin) are present in the sera of asthmatics, correlating with clinical
      disease. Epithelial damage from airway inflammation during asthma may result in
      the exposure of cryptic self-antigens or their determinants, resulting in immune
      response to self-antigens, which may contribute to the pathogenesis of asthma.

PMID- 22386693
TI  - FCRL3 gene polymorphisms contribute to the radiographic severity rather than
      susceptibility of rheumatoid arthritis.
AB  - The ethnic heterogeneity and genetic complexity of rheumatoid arthritis (RA) have
      produced inconsistent results in previous genetic association studies concerning
      FCRL3. This study sought to delineate the association between the FCRL3 gene
      polymorphisms and susceptibility to RA and to investigate the effects of the
      polymorphisms on the progression of joint destruction in RA. RA patients (n =
      377) and healthy unrelated controls (n = 298) were recruited. Genotyping of -169
      T>C and -110 G>A in the promoter and 1,381 G>A in the intron was accomplished
      using FRET assays. The distribution of genotypes and haplotypes did not differ
      between RA patients and controls. When we investigated the role of FCRL3
      polymorphisms for the severity of RA, patients with the CC genotype in the -169
      T>C polymorphism had a higher modified Sharp score than other genotype groups (p
      = 0.034) among patients with disease duration >=10 years. The slope of the
      regression line for modified Sharp score over disease duration (10.12/year) was
      significantly steeper in patients with the CC genotype than in the T carriers
      (5.69/year) at the -169 T>C polymorphism (p = 0.003), indicating the faster
      progression of radiologic destruction in the CC genotype. In conclusion,
      polymorphisms of the FCRL3 gene may contribute to the progression of joint
      destruction rather than susceptibility of RA.

PMID- 22386694
TI  - Plasmacytoid dendritic cells and their Toll-like receptor 9 expression
      selectively decrease with age.
AB  - Dendritic cells (DCs) play a crucial role in the initiation of immune responses
      against infectious particles and tumor cells; however, the impact of age,
      anthropometric parameters, and gender on the number and the expression of
      function-associated molecules of human DCs is poorly understood. In this study,
      blood DCs of 50 volunteers (19-84 years old) with no acute or chronic
      inflammatory diseases were examined using 4-color flow cytometry. Increasing age
      was associated with a decrease in blood plasmacytoid, but not myeloid DCs and a
      selective decrease in Toll-like receptor 9 (TLR9) expression by plasmacytoid DCs.
      In contrast, gender and body mass index did not impact the number of DC subsets
      or the expression of function-associated DC molecules. Thus, we demonstrate that
      age has a selective impact on plasmacytoid DCs and their TLR9 expression. This
      may contribute to an increased susceptibility to infections and tumors with
      increasing age.

PMID- 22386695
TI  - MicroRNAs regulate and provide robustness to the myogenic transcriptional
      network.
AB  - The genetics of skeletal muscle lineage commitment are deceptively complicated.
      MyoD overexpression is sufficient to convert fibroblasts into skeletal muscle
      myotubes. In vivo, there are a number of different steps of differentiation that
      require a large network of transcription factors that control differentiation and
      homeostasis of skeletal muscle progenitors. Each transcription factor has been
      shown to have the ability to promote the next factor in the cascade, but the
      mechanisms regulating the transitions remain incomplete. Recently, microRNAs have
      been shown to be important for a large number of developmental and oncogenic
      processes. In this review, we will discuss recent advances in the understanding
      of how microRNA is critical for skeletal muscle development by interacting with
      protein-coding genes that had previously been shown to be important for
      myogenesis.

PMID- 22386697
TI  - Ultraviolet irradiation modulates ABO blood group antigens in human skin in vivo:
      possible implication in skin aging.

PMID- 22386696
TI  - DKK1 is highly expressed in the dermis of vitiligo lesion: is there association
      between DKK1 and vitiligo?

PMID- 22386698
TI  - The influence of renal function on the prognostic value of NT-pro brain
      natriuretic peptide in ST-elevation myocardial infarction.

PMID- 22386699
TI  - Acute effect of sildenafil on central hemodynamics in mechanically ventilated
      patients with WHO group III pulmonary hypertension and right ventricular failure
      necessitating administration of dobutamine.
AB  - BACKGROUND/OBJECTIVES: Sildenafil decreases pulmonary vascular resistance index
      (PVRI), in patients with pulmonary hypertension (PH). We investigated
      sildenafil's effects on central hemodynamics of mechanically ventilated patients
      with WHO group-III PH and RV failure necessitating dobutamine administration.
      METHODS: Prospective non-controlled study involving 12 (9 males, 59 +/- 4 years
      old), patients with the above characteristics. All patients in phase-1 (days 1-2)
      received dobutamine (5 MUg/kg/min IV). During phase-2 (days 3-6), sildenafil was
      started via nasogastric tube (80 mg/day) and dobutamine discontinuation was
      attempted. Patients were designated responders or non-responders based on whether
      dobutamine could be stopped or not. Phase-3 lasted from day 7 to day of weaning
      from mechanical ventilation; or if weaning failed, until day 20 following
      admission (end-of-study). Invasive and echocardiographic parameters were
      repeatedly recorded throughout the study. RESULTS: Significantly changed
      parameters (P<0.025) from baseline to phase-1, -2 and -3 (%change of mean
      ratios), in responders (n=7) included among others PVRI (-40%, -51%, -42%), RV
      stroke work index (RVSWI: 43%, 79%, 41%) and cardiac index (49%, 54%, 48%), which
      also differed significantly from non-responders (N=5). In phases-1 and -3 non
      responders had not significant changes, in phase-2 PVRI (27%) and RVSWI (-22%)
      changed significantly. In contrast to non-responders, all responders were weaned
      from mechanical ventilation until the end-of-study (P<0.025). CONCLUSIONS:
      Sildenafil may improve central hemodynamics and RV function indices in ventilated
      patients with WHO group-III PH and RV failure requiring dobutamine infusion, when
      they respond favorably to the latter. Accordingly, an adequate RV systolic
      reserve may be mandatory for sildenafil to exert its actions.

PMID- 22386700
TI  - Risk of stroke associated with inhaled ipratropium bromide in chronic obstructive
      pulmonary disease: a population-based nested case-control study.
AB  - BACKGROUND: Cardiovascular safety concerns about inhaled ipratropium bromide have
      recently been raised. Nonetheless, the specific stroke risk associated with
      ipratropium use has not been evaluated thoroughly. METHODS: This was a population
      based nested case-control study analyzing data from the National Health Insurance
      Research Database in Taiwan. A cohort of 15,396 newly-diagnosed chronic
      obstructive pulmonary disease (COPD) patients was included between 2001 and 2007,
      in which 1477 cases of incident hospitalization for stroke were identified. Each
      case was individually matched to four randomly-selected controls based on age,
      sex, and cohort entry date. Conditional logistic regressions were used to
      estimate the odds ratio (OR) for risk of stroke-related hospitalization
      associated with ipratropium use. RESULTS: Any use of ipratropium within the 6
      months before the index date was associated with an increased risk of stroke
      compared with nonuse (adjusted OR, 2.02; 95% CI, 1.71 to 2.41). The observed risk
      remained significant regardless of accumulated doses. Additionally, use of
      ipratropium within 30 days before the index date resulted in the greatest risk
      (adjusted OR, 2.97 95% CI, 2.27 to 3.88). Furthermore, an increased risk of
      stroke was found for ipratropium regimens involving concomitant use of inhaled
      short-acting beta(2)-agonists (SABAs; adjusted OR, 2.18; 95% CI, 1.81 to 2.62) or
      theophyllines (adjusted OR, 1.79; 95% CI, 1.42 to 2.26). CONCLUSIONS: Use of
      ipratropium is associated with an increased risk of stroke in COPD patients.
      Clinicians should be alert to that risk when prescribing ipratropium, especially
      for those receiving ipratropium more recently or those with concomitant use of
      SABAs or theophyllines.

PMID- 22386702
TI  - Telmisartan reduces triglyceride levels over other angiotensin II receptor
      blockers: a meta-analysis of randomized head-to-head trials.

PMID- 22386701
TI  - Relationship between myocardial bridges and reduced coronary atherosclerosis in
      patients with angina pectoris.
AB  - BACKGROUND: A myocardial bridge (MB) is a band of myocardium covering a coronary
      artery segment, typically located in the left anterior descending coronary artery
      (LAD). Bridged segments of the coronary artery are isolated from the influence of
      perivascular adipose tissue. The aims of this study were to investigate the
      relationship between MBs and atherosclerosis in bridged LAD segments and to
      evaluate whether perivascular adipose tissue is involved in this relationship.
      METHODS: MBs were identified in the coronary arteries of patients referred for
      diagnostic cardiac CT. The calcium score of MBs of the LAD or, in patients
      without LAD-MBs, of a corresponding LAD segment at the same distance from its
      origin and over the same length was measured. RESULTS: Of 128 patients, 56 (44%)
      had in total 73 MBs. The mean MB length was 22 +/- 14 mm and the median MB
      thickness was 0.8mm (interquartile range 0.3-2.1mm). MBs in the LAD were present
      in 40 patients (31%). The calcium score was 0 in 95% of the LAD segments with MBs
      compared with 52% of the corresponding LAD segments without MBs. The association
      between LAD-MBs and calcium score (OR 0.06, 95% CI 0.01-0.25) was not influenced
      by age and gender, but was attenuated by local perivascular adipose tissue
      thickness (OR 0.35, 95% CI 0.04-2.70). CONCLUSIONS: Coronary artery segments
      covered with an MB have a lower calcium score than segments without an MB. The
      association between MBs and calcium scores was influenced by local perivascular
      adipose tissue thickness.

PMID- 22386703
TI  - Heart rate variability is associated with glycemic status after controlling for
      components of the metabolic syndrome.
AB  - OBJECTIVE: To evaluate the relationship between heart rate variability (HRV) and
      glycemic status after controlling for metabolic syndrome (MetS) in a healthy
      working cohort. BACKGROUND: A growing body of literature suggests that reduced
      HRV, a physiological marker of autonomic nervous system activity, is associated
      with various pathological conditions including glycemic disorders and
      cardiovascular diseases. The extent to which this association is confounded by
      other more traditional markers of cardiovascular risk, such as MetS, is unclear.
      METHODS: We recruited 2441 study participants (age 17-65) employed at three sites
      of an airplane manufacturing plant in southern Germany. All subjects underwent
      medical examination, blood sampling, and 24-hour ambulatory heart rate recording
      while on their normal work routine. Indices of HRV were determined from readings
      made throughout the 24-hour examination period, those during either the day or
      night only as well as a night to day ratio. Pearson correlations and multivariate
      adjusted partial correlation coefficients (PCCs) were calculated. RESULTS:
      Pearson correlations suggested inverse associations between HRV measurements and
      glycemic status (e.g. High frequency r=-0.07, p<0.001; SDNN r=-0.09, p<0.001).
      After multivariate adjustment of all other components of MetS (triglyceride,
      blood pressure, waist circumference, high density lipoproteins), medical and
      demographic variables, these associations persisted (e.g. High frequency PCC=
      0.05, p<0.001; SDNN PCC=-0.06, p<0.001). CONCLUSIONS: We confirm a negative
      correlation between HRV and glycemic status that appeared to be almost linear in
      a large cohort of healthy workers. Importantly, we showed that this association
      was independent of potential confounders, especially all of the MetS components
      and inflammation.

PMID- 22386704
TI  - Severe corrosion after malpositioning of a metallic head over the Morse taper of
      a cementless hip arthroplasty. A case report.
AB  - Morse tapers are frequently used in total hip replacement to achieve precise
      adjustment of lengths and femoral offset. Mechanically, they do not raise any
      specific problems so long as strict positioning requirements are observed and
      elements from different manufacturers are not mixed together. We report a case in
      which the implant induced unexplained pain at 2 years, in relation to a defective
      fit between the metallic head and the Morse taper. Asymmetric partial fit of the
      head onto the taper was detected on control X-ray and was implicated as causing
      metallosis due to excessive release of metal debris from the Morse taper.
      Revision required femoral stem exchange because of the damage to the Morse taper
      as well as replacing the cup with new metal-metal bearings. Evolution was
      favorable at 3 years' follow-up. Most hip replacements include a Morse taper; the
      present clinical case is a reminder that strict positioning rules are to be
      respected, without which corrosion and wear may lead to mechanical failure.

PMID- 22386705
TI  - Inferior paralabral ganglion cyst of the shoulder with labral tear -- a rare
      cause of shoulder pain.
AB  - INTRODUCTION: Paralabral ganglion cysts of the shoulder are rare, and their
      pathogenesis is similar to that of meniscal cysts. The paralabral cysts are most
      frequently reported along the posterior, superior, and anterior aspects of the
      glenohumeral joint and are uncommon inferiorly to the joint. These cysts rarely
      become evident clinically, unless they cause compression of surrounding
      structures, i.e. nerve. PATIENTS AND METHODS: We report a retrospective series of
      five patients with inferior paralabral ganglion cysts of the shoulder without
      compression of the surrounding nerve which were treated during the period from
      March 2007 to December 2009. All these patients presented with only chronic
      shoulder pain as their chief complaint, and preoperative MRI showed the cyst over
      the inferior aspect of a torn glenoid labrum. All patients were treated by
      arthroscopic cystic decompression with labrum repair. All patients were re
      evaluated with MRI performed at an average of 15 months postoperatively. The
      clinical outcome, including the Constant score, was assessed for all patients at
      a median of 16 months postoperatively. RESULTS: All the five patients had
      remission of pain and were satisfied with the shoulder function. The
      postoperative MRI in all patients showed no labral cyst recurrence. The median
      Constant score improved from a preoperative level of 81.5 points to 98.0 points
      at last follow-up. CONCLUSION: This study demonstrates that, in the absence of
      any nerve compression symptoms around the shoulder joint, inferior paralabral
      cysts with labral tear also be considered in the differential diagnosis of
      chronic shoulder pain. Arthroscopic repair of the cyst with repair of the labrum
      can lead to the disappearance of symptoms. Knowledge of this clinical condition
      and its imaging features is critical for a correct diagnosis of this uncommon
      cause of chronic shoulder pain. LEVEL OF EVIDENCE: Level IV. Retrospective
      therapeutic study.

PMID- 22386706
TI  - Genomic and functional characterization of the diverse immunoglobulin domain
      containing protein (DICP) family.
AB  - A heretofore-unrecognized multigene family encoding diverse immunoglobulin (Ig)
      domain-containing proteins (DICPs) was identified in the zebrafish genome. Twenty
      nine distinct loci mapping to three chromosomal regions encode receptor-type
      structures possessing two classes of Ig ectodomains (D1 and D2). The sequence and
      number of Ig domains, transmembrane regions and signaling motifs vary between
      DICPs. Interindividual polymorphism and alternative RNA processing contribute to
      DICP diversity. Molecular models indicate that most D1 domains are of the
      variable (V) type; D2 domains are Ig-like. Sequence differences between D1
      domains are concentrated in hypervariable regions on the front sheet strands of
      the Ig fold. Recombinant DICP Ig domains bind lipids, a property shared by
      mammalian CD300 and TREM family members. These findings suggest that novel
      multigene families encoding diversified immune receptors have arisen in different
      vertebrate lineages and affect parallel patterns of ligand recognition that
      potentially impact species-specific advantages.

PMID- 22386707
TI  - Sniff nasal inspiratory pressure and sleep disordered breathing in childhood
      neuromuscular disorders.
AB  - The ease of sniff nasal inspiratory pressure testing may extend application of
      respiratory muscle assessment to younger and cognitively-impaired children. We
      sought to quantify sniff nasal inspiratory pressure in childhood neuromuscular
      disorders, and to correlate this measure with conventional pulmonary function
      tests and overnight polysomnography. Thirty children (mean 9.7 +/- 3.8 years,
      range 4.3-16.5 years) with diagnosed neuromuscular disorders (Duchenne muscular
      dystrophy, spinal muscular atrophy, Becker muscular dystrophy, congenital
      myopathy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, multi
      minicore disease) underwent assessment. Thirty-seven percent displayed cognitive
      impairment. Those with neuromuscular disorders were then compared with 32
      volunteer age- and gender-matched controls (mean 10.9 +/- 2.9 years, range 6.6
      17.2 years) with normal respiratory function. Twenty-three children with
      neuromuscular disorders also underwent overnight polysomnography. Children with
      neuromuscular disorders demonstrated significantly impaired sniff nasal
      inspiratory pressure, maximal inspiratory pressure, FEV(1) and FVC (p<0.05). A
      positive correlation was identified between daytime sniff nasal inspiratory
      pressure and maximal inspiratory pressure (r=0.58), FEV(1) (r=0.55) and FVC
      (r=0.46), though not with polysomnography variables (respiratory disturbance
      index, nadir SpO(2), peak CO(2)). Moderate prevalence of nocturnal hypoxia was
      observed, and 32% of children demonstrated sleep disordered breathing. Sniff
      nasal inspiratory pressure assessment was well tolerated, representing a
      promising surrogate measure for assessment of respiratory function in childhood
      neuromuscular disorders.

PMID- 22386708
TI  - Sentinel lymph node biopsy in management of early breast cancer: Is it rational
      to omit blue dye injection?

PMID- 22386709
TI  - Intestinal and multivisceral autotransplantation for tumors of the root of the
      mesentery: Long-term follow-up.
AB  - OBJECTIVE: To present the indications, techniques, short- and long-term outcomes
      after visceral exenteration, ex vivo resection, and intestinal/multivisceral
      autotransplantation. PATIENTS AND METHODS: All patients who have undergone this
      procedure at our center were studied. Technique, postoperative complications,
      survival, tumor recurrence, and functional status were recorded. RESULTS: Ten
      patients, 4 children and 6 adults, have undergone these procedures since January
      1999. Seven patients are alive at 13-138 months later, 6 with functioning
      autografts and one after rescue with an allotransplantation. CONCLUSION:
      Intestinal/multivisceral autotransplantation is a potentially valuable option for
      some otherwise unresectable neoplasms of the root of the mesentery.

PMID- 22386710
TI  - Unique moments in time: what patients teach us.

PMID- 22386711
TI  - Spleen-preserving distal pancreatectomy with splenic vessels excision.

PMID- 22386712
TI  - Laryngeal approach to the recurrent laryngeal nerve involved by thyroid cancer at
      the ligament of Berry.
AB  - BACKGROUND: Thyroid cancer often involves the RLN at the ligament of Berry, which
      makes preservation of the nerve difficult. If the portion of RLN is resected,
      finding the peripheral RLN for reconstruction is difficult. Here we describe a
      laryngeal approach performed before dissecting the RLN to overcome these
      problems. METHODS: Between January 2007 and April 2011, 13 patients with
      papillary thyroid carcinoma had unilateral RLN involvement by the cancer at the
      ligament of Berry. Preoperatively, 8 had functioning vocal cords and 5 had
      unilateral paralysis. The laryngeal approach involves dividing the inferior
      pharyngeal constrictor muscle along the lateral edge of the thyroid cartilage and
      identifying the nerve under the muscle or behind the thyroid cartilage. This
      procedure was performed before resecting the tumor in 10 patients (Group 1) and
      after resection in the remaining 3 (Group 2). RESULTS: In Group 1, the RLN could
      be preserved with sharp dissection in 3 with functioning vocal cords
      preoperatively. Postoperatively they restored vocal cord function. The remaining
      7 needed resection of the portion of RLN. RLN reconstruction was easily, since
      the peripheral RLN had already been identified. All patients in Group 2 needed
      resection of the portion of RLN. The peripheral RLN was identified in 2, and ansa
      RLN anastomosis was performed. However, this was not possible in 1 patient.
      CONCLUSION: In patients with thyroid cancer involving the RLN at the ligament of
      Berry, performing the laryngeal approach before dissecting the nerve facilitates
      preservation or reconstruction of the nerve.

PMID- 22386713
TI  - A 5-year review of a trauma-trained hospitalist program for trauma patients: A
      matched cohort study.
AB  - BACKGROUND: Level I trauma centers have requirements on the percentage of trauma
      patients admitted to either a trauma surgeon or surgical subspecialist; however,
      surgical resources are in steady decline. Therefore, a trauma system might better
      utilize its surgical resources if trained hospitalists admitted a larger
      percentage of mild to moderately injured trauma patients. The objective of this
      report is to provide a 5-year evaluation of a trauma medical service (TMED) at
      treating mild to moderately injured trauma patients. METHODS: Adult trauma
      patients consecutively admitted to a Level I trauma center between January 2006
      and December 2010 were analyzed. Patients admitted to trauma surgical services
      were matched 1:1 to those admitted to TMED, via propensity scores. Paired t tests
      examined differences in hospital duration of stay (DOS), and exact conditional
      logistic regression examined differences in the odds of having a delayed
      diagnosis, developing a complication, and dying. RESULTS: Of 1,202 TMED patients,
      494 were matched; matched TMED patients had similar patient outcomes to
      nonmatched TMED patients. There were no differences between study groups in the
      mean hospital DOS, the proportion having a delayed diagnosis, or in the odds of
      dying in the hospital (P > .05 for all). The TMED group had a nominally higher
      complication rate (P = .12) owing to a higher rate of urinary tract infections.
      CONCLUSION: Since its inception, the TMED service has successfully and safely
      treated mild to moderately injured trauma patients, and decreased the dependency
      on trauma surgical services. Trauma centers might utilize declining surgical
      services more efficiently with the addition of trauma medical hospitalists.

PMID- 22386715
TI  - Thyroid function in PMM2-CDG: diagnostic approach and proposed management.
AB  - Glycoproteins are essential in the production, transport, storage and regulation
      of thyroid hormones. Altered glycosylation has a potential impact on thyroid
      function. Abnormal thyroid function tests have been described in patients with
      congenital disorders of glycosylation. We evaluated the reliability of
      biochemical markers and investigated thyroid function in 18 PMM2-CDG patients. We
      propose an expectative therapeutic approach for neonates with thyroid
      abnormalities in CDG.

PMID- 22386716
TI  - L-3-n-butylphthalide improves cognitive deficits in rats with chronic cerebral
      ischemia.
AB  - 3-n-Butylphthalide (NBP) has been shown to have protective effects against
      ischemic stroke. In the present study, we investigated effects of l-3-n
      butylphthalide (l-NBP) on the learning and memory impairment induced by chronic
      cerebral ischemia in rats. Male Wistar rats were administered 20 mg/kg l-NBP by
      gavage daily for 30 days after the bilateral common carotid artery clamping (two
      vessel occlusion, 2-VO). Results showed that daily treatments of 20 mg/kg l-NBP
      significantly attenuated spatial learning deficits in Morris water maze (MWM)
      task. Results of long-term potentiation (LTP) indicated that treatment with 20
      mg/kg l-NBP attenuated the inhibition of LTP in rat model of 2-VO. Moreover, l
      NBP reduced glial fibrillary acidic protein (GFAP)-positive astrocytes induced by
      chronic cerebral ischemia. The present findings demonstrate the protective effect
      of l-NBP on chronic cerebral ischemia-induced hippocampus injury, which supports
      using l-NBP for therapy of cerebral ischemia in the future.

PMID- 22386717
TI  - 1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli
      dihydrodipicolinate synthase.
AB  - Dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway
      that catalyzes the condensation of pyruvate and aspartate semi-aldehyde. A series
      of phenolic ketoacid derivatives that mimic the proposed enzymatic intermediate
      were designed as potential inhibitors of this enzyme and were synthesized from
      simple precursors. The ketoacid derivatives were shown to act as slow and slow
      tight binding inhibitors. Mass spectrometric experiments provided further
      evidence to support the proposed model of inhibition, demonstrating either an
      encounter complex or a condensation product for the slow and slow-tight binding
      inhibitors, respectively.

PMID- 22386718
TI  - Use of computed tomography and silicon endocasts to identify pulmonary veins with
      echocardiography.
AB  - The pulmonary veins were identified from the silicone endocast heart models of 19
      dogs. Although variation in the number of the more peripheral veins on each
      specimen existed, all of the casts had a consistency with regards to the most
      proximal coalescence of the pulmonary veins as they entered the body of the left
      atrium. That is, the confluence of the veins formed three ostia at the atrial
      entry point that consisted of 1) right cranial and right middle pulmonary lobe
      veins; 2) right caudal, accessory, and left caudal pulmonary lobe veins; and 3)
      both the left cranial and left caudal pulmonary lobe veins of the left cranial
      lung lobe. The location of these structures identified by the 3-dimensional
      endocasts were then used to assist in the identification of the pulmonary veins
      using computed tomography of 2 dogs. Slices were made that approximated those
      commonly performed during echocardiographic examination. Understanding which
      pulmonary veins are seen by echocardiography in the different imaging planes will
      permit prospective evaluations of pulmonary vein size and abnormal flow patterns.

PMID- 22386719
TI  - Left ventricular remodeling in preclinical experimental mitral regurgitation of
      dogs.
AB  - Dogs with experimental mitral regurgitation (MR) provide insights into the left
      ventricular remodeling in preclinical MR. The early preclinical left ventricular
      (LV) changes after mitral regurgitation represent progressive dysfunctional
      remodeling, in that no compensatory response returns the functional stroke volume
      (SV) to normal even as total SV increases. The gradual disease progression leads
      to mitral annulus stretch and enlargement of the regurgitant orifice, further
      increasing the regurgitant volume. Remodeling with loss of collagen weave and
      extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the
      cross-sectional area and length of the cardiomyocyte. Isolated ventricular
      cardiomyocytes demonstrate dysfunction based on decreased cell shortening and
      reduced intracellular calcium transients before chamber enlargement or decreases
      in contractility in the whole heart can be clinically appreciated. The genetic
      response to increased end-diastolic pressure is down-regulation of genes
      associated with support of the collagen and ECM and up-regulation of genes
      associated with matrix remodeling. Experiments have not demonstrated any
      beneficial effects on remodeling from treatments that decrease afterload via
      blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase
      inhibition have altered the progression of the LV remodeling and have supported
      cardiomyocyte function. The geometry of the LV during the remodeling provides
      insight into the importance of regional differences in responses to wall stress.

PMID- 22386721
TI  - Hemostatically distinct FFPs equally improve abnormal TEG variables in an in
      vitro dilutional coagulopathy model.
AB  - INTRODUCTION: To improve fresh frozen plasma (FFP) availability, thawed plasma is
      stored at 4 degrees C for up to 5 days and considered equivalent to freshly
      thawed FFP. However, we have shown that hemostatic potential of thawed plasma is
      highly variable between donors and significantly diminished during storage. We
      hypothesized that smaller volumes of plasma with higher hemostatic potential (FFP
      H) would be needed to restore normal thrombelastogram (TEG) values compared to
      plasma with lower hemostatic potential (FFP-L). MATERIALS AND METHODS: A
      dilutional coagulopathy model was established from whole blood by diluting plasma
      with saline to 23%, while cellular components were kept unchanged. Saline was
      gradually replaced with equal volumes of FFPs with distinctive hemostatic
      potentials, which was evaluated by the calibrated automated thrombogram. Clot
      formation in the presence of tissue factor was evaluated by TEG at baseline and
      after addition of increasing concentrations of FFP-H and FFP-L. RESULTS: Blood
      dilution with saline in the presence of tissue factor resulted in abnormal TEGs
      that resemble a pattern observed in severely bleeding trauma patients. All FFPs
      produced similar improvements in TEG variables despite different hemostatic
      potentials. TEG changes were solely dependent on FFP volume and reached the
      normal reference range when plasma concentration increased to 40%. CONCLUSION:
      Plasma dilution and tissue factor in whole blood results in an abnormal TEG with
      a hyperfibrinolytic pattern. A plasma concentration of at least 40% was necessary
      for TEG normalization after dilution with saline. An effect of FFPs' hemostatic
      potential on clot formation could not be detected by TEG in this in vitro model.

PMID- 22386722
TI  - Association of ADIPOQ gene polymorphisms and coronary artery disease risk: a meta
      analysis based on 12 465 subjects.
AB  - INTRODUCTION: Coronary artery disease (CAD) is one of the most common
      cardiovascular diseases and is a major cause of morbidity and mortality
      worldwide. Various researchers have investigated the role of ADIPOQ gene in the
      risk of CAD, yet their results have been inconsistent. METHODS: To evaluate the
      association between ADIPOQ genetic polymorphisms and CAD risk, relevant studies
      published before October 2011 were identified by searching PubMed and EMBASE.
      Studies were selected using previously defined criteria. The strength of the
      relationship between the four single nucleotide polymorphisms (SNPs) of the
      ADIPOQ gene and CAD risk was assessed using odds ratios (ORs). RESULTS: A total
      of 12 465 subjects from 17 case-control studies were identified in the present
      study. Based on the relevant studies, it was determined that the risk of CAD was
      not associated with rs2241766 in any genetic model. Increased risk of CAD was
      associated with rs266729 in allele contrast (1.11, [1.03, 1.20]) and dominant
      genetic model (1.15, 95%CI: [1.05, 1.27]); increased risk of CAD was also
      associated with rs822395 in additive (1.63, 95%CI: [1.19, 2.22]) and recessive
      genetic model (1.71, 95%CI: [1.27, 2.30]). It was further determined that the
      rs1501299 polymorphism reduced the risk of CAD in the additive (0.80, 95%CI:
      [0.67, 0.94]) and recessive genetic model (0.81, 95%CI: [0.68, 0.95]). In the
      stratified analysis, significant associations were found in Asian subjects for
      rs266729 and in Caucasian subjects for rs1501299. CONCLUSION: There is an
      association between ADIPOQ gene polymorphisms and CAD risk. Different SNPs of the
      ADIPOQ gene have different associations with CAD risk, and appear to increase
      risk in individuals of Asian ethnicity while decrease the CAD risk in Caucasians.
      However, the overall strength of association was mild to moderate.

PMID- 22386723
TI  - The dosimetric impact of heterogeneity corrections in high-dose-rate 192Ir
      brachytherapy for cervical cancer: Investigation of both conventional Point-A and
      volume-optimized plans.
AB  - PURPOSE: To evaluate the dosimetric impact of heterogeneity corrections on both
      conventional and volume-optimized high-dose-rate (HDR) 192Ir brachytherapy tandem
      and-ovoid treatment plans. METHODS AND MATERIALS: Both conventional and volume
      optimized treatment plans were retrospectively created using eight unique CT data
      sets. In the volume-optimized plans, the clinical target volume (CTV) and organs
      at-risk (rectum, bladder, and sigmoid) were contoured on the CT data sets by a
      single physician. For each plan, dose calculations representing homogeneous water
      medium were performed using the Task Group (TG-43) formalism and dose
      calculations with heterogeneity corrections were performed using a commercially
      available treatment planning system. RESULTS: For the conventional plans, the
      change in dose between TG-43 and heterogeneity-corrected calculations was
      assessed for the following points: Point-A (left and right) and International
      Commission on Radiation Units and Measurements (ICRU) 38 defined rectum and
      bladder points. It was found that the dose to the ICRU bladder decreased the most
      (-2.2+/-0.9%), whereas ICRU rectum (-1.7+/-0.8%), Point-A right (-1.1+/-0.4%),
      and Point-A left (-1.0+/-0.3%) also showed decreases with heterogeneity-corrected
      calculations. For the volume-optimized plans, the change in dose between TG-43
      and heterogeneity-corrected calculations was assessed for the following dose
      volume histogram parameters: D(90) of the CTV and D(2cc) of the rectum, bladder,
      and sigmoid. It was found that D(90) of the CTV decreased by -1.9+/-0.7% and
      D(2cc) decreased by -2.6+/-1.4%, -1.0+/-0.4%, and -2.0+/-0.6% for the rectum,
      bladder and sigmoid, respectively, with heterogeneity-corrected calculations.
      CONCLUSIONS: Heterogeneity corrections on high-dose rate plans were found to have
      only a small dosimetric impact over TG-43-based dose calculations for both
      conventional Point-A and volume-optimized plans.

PMID- 22386724
TI  - Volume matters: bladder injections of botulinum toxin type A.

PMID- 22386725
TI  - Re: Antonella Giannantoni, Vittorio Bini, Roger Dmochowski, et al. Contemporary
      management of the painful bladder: a systematic review. Eur Urol 2012;61:29-53.

PMID- 22386726
TI  - Comparative evaluation of the resolution of hydronephrosis in children who
      underwent open and robotic-assisted laparoscopic pyeloplasty.
AB  - OBJECTIVES: To assess long-term postoperative ultrasonographic outcomes of
      robotic-assisted laparoscopic pyeloplasty (RALP) and of conventional open
      pyeloplasty (COP) in pediatric patients with ureteropelvic junction obstruction.
      METHODS: Retrospective review of 312 patients who underwent RALP or COP in a
      single institution. Preoperative and postoperative ultrasounds were used to
      determine the grade of hydronephrosis. Postoperative assessment included 3
      ultrasounds at 0-6, 6-12 and >12 months intervals. Patients were matched by age,
      etiology of obstruction, grade of preoperative hydronephrosis and gender for case
      matched analysis. RESULTS: We identified 212 pyeloplasties that met inclusion
      criteria, being 58 RALP and 154 COP. Groups were different in age, gender and
      etiology, but similar in severity of hydronephrosis and follow-up time. At the
      end of follow-up, complete resolution and success rates were 62% and 74% in RALP
      and 45% and 70% in COP, respectively. Matching included 105 patients. Complete
      resolution was higher in RALP (p = 0.004), while median time before improvement
      was lower (12.3 months RALP vs 29.9 months COP). There was no difference in
      success rate at the end of follow-up between the groups. CONCLUSION: RALP shows
      satisfactory long-term outcomes, comparable to COP. In our cohort, patients who
      underwent robotic pyeloplasty showed faster resolution of hydronephrosis on
      ultrasound.

PMID- 22386727
TI  - Effects of prenatal polycyclic aromatic hydrocarbon exposure and environmental
      tobacco smoke on child IQ in a Chinese cohort.
AB  - OBJECTIVE: This study of a birth cohort in the city of Tongliang in Chongqing,
      China, evaluated the relationship between two prenatal exposures (polycyclic
      aromatic hydrocarbons(PAH) and environmental tobacco smoke(ETS)) and child
      intelligence quotient (IQ) as measured by the Wechsler Preschool and Primary
      Scale of Intelligence at age 5 years. A coal-fired power plant was the major
      source of ambient PAH in this city. We tested the hypothesis that, after
      adjusting for potential confounders, prenatal exposure to these pollutants would
      be associated with lower IQ scores at 5 years of age. METHODS: Nonsmoking mothers
      and children were enrolled before delivery. PAH exposure was measured by DNA
      adducts in umbilical cord white blood cells using High-Performance Liquid
      Chromatography-Fluorescence. Estimated exposure to environmental tobacco smoke
      was based on personal interview. At age 5 years, scores for verbal, performance,
      and full scale IQ were obtained. Multiple regression was used to test the main
      effects of adducts and environmental tobacco smoke on IQ and to explore the
      interactions between these exposures on IQ. RESULTS: after adjusting for
      potential confounders, neither DNA adducts nor exposure to environmental tobacco
      smoke had significant main effects on IQ. However, significant interactions
      between adducts and environmental tobacco smoke were observed on full scale
      (p=0.025) and verbal (p=0.029) IQ scores, indicating that the adverse effects of
      prenatal PAH exposure became greater as exposure to environmental tobacco smoke
      increased. The interaction on performance IQ score was not significant (p=0.135).
      CONCLUSION: These results suggest that exposure of pregnant women to emissions of
      PAHs from the coal-burning plant, in combination with prenatal exposure to
      envrionmental tobacco smoke, may have adversely affected cognitive function of
      children at age 5. The polluting coal-fired plant has since been closed by the
      government, with likely important benefits to child health and development.

PMID- 22386728
TI  - In vivo efficacy of the diuretic agent ethacrynic acid against multiple myeloma.
AB  - It was recently confirmed that the diuretic agent ethacrynic acid (EA) inhibits
      Wnt/beta catenin signaling in myeloma. This study investigated the antitumor
      effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was
      significantly reduced and overall survival significantly prolonged in mice
      treated with EA as compared to untreated mice. Interestingly, this effect was
      higher as compared to the effect by lenalidomide, a commonly used drug against
      myeloma. These results reveal a significant in vivo effect by EA against myeloma.

PMID- 22386729
TI  - Seroreactivity to LGL leukemia-specific epitopes in aplastic anemia,
      myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria: results of a
      bone marrow failure consortium study.
AB  - Large granular lymphocyte (LGL) leukemia is characterized by clonal expansion of
      antigen-activated cytotoxic T cells (CTL). Patients frequently exhibit
      seroreactivity against a human T-cell leukemia virus (HTLV) epitope, BA21.
      Aplastic anemia, paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome
      are bone marrow failure diseases that can also be associated with similar
      aberrant CTL activation (LGL-BMF). We identified a BA21 peptide that was
      specifically reactive with LGL leukemia sera and found significantly elevated
      antibody reactivity against the same peptide in LGL-BMF sera. This finding of
      shared seroreactivity in LGL-BMF conditions and LGL leukemia suggests that these
      diseases might share a common pathogenesis.

PMID- 22386730
TI  - Angiogenic activity of classical hematopoietic cytokines.
AB  - Hematopoiesis is regulated by several cytokines with pleiotropic activity.
      Several evidences have clearly demonstrated that these molecules, formerly
      regarded as specific for the hematopoietic system, also affect certain
      endothelial cell functions and that hematopoietic factors clearly influence
      angiogenesis. This review article summarizes the most important literature data
      concerning this inconvertible relationship.

PMID- 22386731
TI  - Long-term remission in a case of acute promyelocytic leukemia patient with marked
      myelofibrosis treated with arsenic trioxide, all-trans retinoic acid and
      consolidation therapy with daunorubicin plus cytarabine.

PMID- 22386732
TI  - The pharmacology of curcumin: is it the degradation products?
AB  - The natural product curcumin has gained considerable attention in recent years
      for its multiple pharmacological activities, but more efforts are needed to
      understand how curcumin can have these pharmacological effects considering its
      low bioavailability. In addition, it is unclear how curcumin exerts inhibitory
      effects against numerous enzymes, especially those that cannot accommodate
      curcumin within recognized binding pockets. By analyzing the similarities between
      the biological activities of curcumin and its degradation products against
      diseases such as Alzheimer's disease and cancer, as well as the preferential
      inhibition of some enzymes by degradation products, it appears that the bioactive
      degradation products may contribute to the pharmacological effects of curcumin.
      This possibility should be given full attention when elucidating the pharmacology
      of this promising natural product for various diseases.

PMID- 22386733
TI  - Absence of evidence for epidermal growth factor receptor and human homolog of the
      Kirsten rat sarcoma-2 virus oncogene mutations in breast cancer.
AB  - AIMS: The epidermal growth factor receptor (EGFR) is an available target of
      effective anti-EGFR therapy for human breast cancer. KRAS, the human homolog of
      the Kirsten rat sarcoma-2 virus oncogene, encodes a main downstream signaling
      molecule in the EGFR pathway. The aim of this study was to assess the presence of
      EGFR and KRAS gene mutations in breast cancer. MATERIALS AND METHODS: EGFR and
      KRAS gene mutations were investigated in formalin-fixed, paraffin-embedded
      tissues from 143 Chinese female patients with breast cancer by means of real-time
      quantitative polymerase chain reaction (RT-PCR). RESULTS: Based on RT-PCR, 2/143
      (1.4%) samples and 1/143 (0.7%) had EGFR and KRAS gene mutations, respectively.
      Overall, none of the cases was identified with mutations of both of these two
      genes. CONCLUSIONS: In this study, both EGFR and KRAS mutations were present
      rarely in this cohort of samples with breast cancer. This suggested that mutation
      analyses for EGFR and KRAS are not useful as screening tests for sensitivity to
      anti-EGFR therapy for breast carcinomas.

PMID- 22386734
TI  - The incidence and relative risk of stroke in patients with schizophrenia: a five
      year follow-up study.
AB  - OBJECTIVE: This study aimed to estimate the incidence and relative risk of stroke
      and post-stroke all-cause mortality in patients with schizophrenia. METHODS: This
      study identified a study population from the National Health Insurance Research
      Database (NHIRD) between 1999 and 2003 that included 80,569 patients with
      schizophrenia and 241,707 age- and sex-matched control participants without
      schizophrenia. The participants were randomly selected from the 23,981,020
      participant NHIRD, which consists of 96% Taiwanese participants. Participants who
      had experienced a stroke between 1999 and 2003 were excluded. Using data from the
      NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and
      patient survival after stroke were calculated for both groups. After adjusting
      for confounding risk factors, a Cox proportional-hazards model was used to
      compare the five-year stroke-free survival rate to the all-cause mortality rate
      across the two cohorts. RESULTS: Over five years, 1380 (1.71%) patients with
      schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting
      for demographic characteristics and comorbid medical conditions, patients with
      schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22;
      P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the
      follow-up period. After adjusting for patient, physician and hospital variables,
      the all-cause mortality hazard ratio for patients with schizophrenia was 1.23
      (95% CI=1.06-1.41; P=0.0052). CONCLUSIONS: During a five-year follow-up, the
      likelihood of developing a stroke and the all-cause mortality rate were greater
      among patients with schizophrenia as compared with the control group.

PMID- 22386735
TI  - Predictors of the accuracy of self assessment of everyday functioning in people
      with schizophrenia.
AB  - Despite multiple lines of evidence suggesting that people with schizophrenia have
      substantial problems in self-reporting everyday functioning and cognitive
      performance, self-report methods are still widely used to assess functioning.
      This study attempted to identify predictors of accuracy in self report, both in
      terms of accurate self-assessment and over-estimation of current functioning. As
      part of the larger Validating Assessments of Everyday Real-World Outcomes
      (VALERO) study, 195 patients with schizophrenia were asked to self report their
      everyday functioning with the Specific Levels of Functioning (SLOF) scale, which
      includes subscales assessing social functioning, everyday activities, and
      vocational functioning. They were also assessed with measures of
      neuropsychological (NP) performance and functional capacity (FC), and were
      assessed for psychiatric symptomatology. In addition, a friend, relative or
      clinician informant was interviewed with the SLOF, and an interviewer with access
      to all information provided by the patient and informant (exclusive of
      performance-based data) generated "best estimate" ratings of actual, everyday
      functioning. Patients significantly (p<.001) overestimated their vocational
      functioning and everyday activities compared to the interviewer judgments. Lower
      levels of NP and FC performance and everyday functioning on the part of patients
      were consistently associated with overestimation of their functioning. Patient
      self-reports were not correlated with any performance-based measures, while
      interviewer judgments were significantly correlated with patients' performance on
      NP and FC measures (p<.005). In regression analyses, adjusting for interviewer
      ratings of functioning, several predictors of the discrepancy between self and
      interviewer judgments emerged. Higher levels of depressive symptoms were
      associated with less overestimation in self-reports (p<.001). Delusions,
      suspiciousness, grandiosity and poor rapport were all significantly (p<.001)
      associated with over-estimation of functioning compared to interviewer judgments.
      Poorer NP and FC performance were also associated with over-estimation of
      everyday functioning, but these results were not statistically significant in
      multivariate regression models. Consistent with previous studies in
      schizophrenia, other neuropsychiatric conditions and non-clinical populations,
      higher levels of depression were associated with increased accuracy in self
      assessment. Similarly, lower scores on performance-based measures and judgments
      of everyday functioning also predicted over-estimation of functioning. Thus, we
      identified bi-directional predictors of mis-estimation of everyday functioning,
      even when poor baseline scores were considered. These data suggest that it may be
      possible to screen patients for their ability to self-report their functioning,
      but that performance-based measures of functioning provide a less biased
      assessment.

PMID- 22386736
TI  - Optimising outcome on thiopurines in inflammatory bowel disease by co
      prescription of allopurinol.
AB  - BACKGROUND AND AIMS: Azathioprine and mercaptopurine remain first line
      immunomodulatory treatments for inflammatory bowel disease. Toxicity and non
      response are significant issues. Co-prescription of allopurinol with reduced-dose
      (25-33%) azathioprine or mercaptopurine may overcome these problems. We present
      the outcome of co-prescription in a large single-centre cohort. METHOD: Patients
      on thiopurine/allopurinol co-prescription were identified. Indication for and
      outcome on combination treatment were established. Blood parameters and
      metabolite results were compared on single agent and combination treatment.
      Toxicity associated with combination treatment was sought. RESULTS: 110 patients
      on combination treatment were identified. Clinical remission was achieved in
      60/79 (76%) of patients in whom the effect of thiopurine could be studied in
      isolation. 20/25 patients with hepatotoxicity tolerated combination treatment and
      normalised their liver function tests. 24/28 patients with atypical side effects
      tolerated co-therapy. 13/20 non-responders responded to combination treatment. In
      patients started on combination treatment as first line therapy, 15/23 achieved
      clinical remission. Thioguanine nucleotides were significantly higher and
      methylated metabolites significantly lower on combination therapy. Mean cell
      volume was higher and total white cell and neutrophil counts lower on combination
      treatment. 13 adverse events occurred, including 6 specific to co-therapy (3
      rash, 2 abnormal liver function tests, 1 dosing error). All were minor and self
      limiting. CONCLUSION: This is the largest published experience of the use of
      allopurinol to optimise outcomes on thiopurine treatment. Combination therapy
      permitted successful treatment of a significant number of patients who would
      otherwise have been labelled as thiopurine failures. A few self-limiting side
      effects were encountered.

PMID- 22386737
TI  - Circulating MicroRNA in inflammatory bowel disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) consist of a group of small noncoding RNAs that
      partially regulate gene expression. We investigated the expression patterns of
      commonly deregulated miRNAs in Crohn's disease (CD) and ulcerative colitis (UC)
      in peripheral blood samples of inflammatory bowel disease patients. PATIENTS AND
      METHODS: This study consisted of 128 CD and 88 UC patients, as well as 162
      healthy controls. The expression patterns of the miRNA species were
      quantitatively assayed using reverse transcription and real-time RT-PCR. Stem
      loop complementary DNAs (cDNAs) were synthesized using looped reverse
      transcription primers specific for each miRNA. RESULTS: MiR-16, miR-23a, miR-29a,
      miR-106a, miR-107, miR-126, miR-191, miR-199a-5p, miR-200c, miR-362-3p and miR
      532-3p were expressed at significantly higher levels in the blood from patients
      with CD compared with the healthy controls. No significant differences were
      observed when the CD patients were classified according to disease location and
      phenotype. In the UC cases three miRNAs (miR-16, miR-21, miR-28-5p, miR-151-5p,
      miR-155 and miR-199a-5p) were significantly increased compared to healthy
      controls. miR-155 was the most highly expressed of the UC-associated miRNA in
      blood samples. CONCLUSIONS: Our results suggest that several miRNAs could
      distinguish CD from UC by real-time PCR. This further highlights the putative
      role of miRNAs as contributors to IBD pathogenesis. They may help develop new non
      invasive biomarkers to distinguish UC and CD.

PMID- 22386738
TI  - The efficacy of intensive granulocyte and monocyte adsorption apheresis in a
      patient with Crohn's disease complicated by extensive subcutaneous aseptic
      neutrophilic abscesses.
AB  - BACKGROUND AND AIMS: Subcutaneous aseptic abscess is one phenotype of
      neutrophilic dermatitis. We were interested to see if a case of steroid
      refractory Crohn's disease (CD) complicated by subcutaneous aseptic neutrophilic
      abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA).
      METHODS: The patient was a 21-year-old male with worsening severe CD while on
      oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and
      multiple painful subcutaneous nodules throughout his body. Skin biopsy showed
      chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed
      oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma.
      Because biologics were feared to increase the risk of bacteraemia as the result
      of germ culture on his pus was not known at the time, we decided to treat this
      case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days
      (daily GMA) were initiated. RESULTS: On admission, his CD activity index (CDAI)
      was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI
      decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at
      2 sessions/week (total 10 sessions). The patient's CDAI fell to <150, and the
      skin lesions re-epithelialized. CONCLUSIONS: In this CD case complicated by
      subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our
      impression is that when biopsy reveals neutrophil infiltrate is a major feature
      of the lesions, GMA should be considered. As GMA appears to have no safety
      concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week
      should be preferred over the routine weekly GMA.

PMID- 22386739
TI  - Cross-sectional study on prevalence of Trypanosoma evansi infection in domestic
      ruminants in an endemic area of the Canary Islands (Spain).
AB  - Trypanosoma evansi is the most widely spread of the pathogenic African
      trypanosomes of animals. The disease (surra) was first diagnosed in the Canary
      Islands in a dromedary camel in 1997; thus, a control plan was implemented
      achieving the eventual eradication of T. evansi from most of the infected areas
      in the Archipelago. However, a little area remains still infected despite the use
      of the same control measures. To evaluate possible reservoirs in the area a
      representative sample of domestic ruminants was examined by serological,
      parasitological and molecular tests. Of a total of 1228 ruminants assessed, 61
      (5%) were serologically positive (7 cattle, 21 goats, 33 sheep), but T. evansi
      could be demonstrated in none of them. According to FreeCalc assessment, cattle
      and goat populations would be free from disease; however, the results from sheep
      are not adequate to conclude that the population would be free from disease. As a
      conclusion, surveillance must be exercised on ruminant farms in the surroundings
      of the infected area in order to evaluate the possible extension of the disease
      and their potential role as reservoirs of T. evansi.

PMID- 22386740
TI  - Case control study to investigate risk factors for bovine neonatal pancytopenia
      (BNP) in young calves in southern Germany.
AB  - A case control study on farm level was conducted at the Clinic for Ruminants, LMU
      Munich, to identify possible risk factors associated with the observed increase
      in numbers of calves showing clinical signs of Bovine Neonatal Pancytopenia (BNP)
      since 2006 in southern Germany. Interviews were conducted between August 2008 and
      June 2010. The characteristics of 56 dairy farms with at least one confirmed case
      of BNP (thrombocytopenia and leukocytopenia and/or typical findings in post
      mortem examination and bone marrow histology) were compared with those of two
      sets of 50 control dairy farms each, with no history of BNP. The first set of 50
      control farms was selected randomly from veterinary practices which had never
      observed a BNP case on the farms they serviced. The second set of 50 control
      farms was matched by the veterinary practices which had provided case farms. Two
      separate analyses were conducted: (1) case farms (n=56) vs. randomly selected
      control farms (n=50) and (2) case farms (n=56) vs. a matched set of control farms
      (n=50). All variables with p<0.2 in the univariable analysis were included in
      stepwise logistic regression models. In the first analysis, only the use of
      PregSure((r)) BVD vaccine was positively associated with BNP with an odds ratio
      of 1292 (95% CI: 114-14707). In the second analysis, conditional logistic
      regression models did not converge, therefore non-conditional logistic regression
      models were conducted. In the non-conditional analysis five variables remained in
      the model, three of which were negatively associated with BNP: the use of vitamin
      E and selenium, the frequent use of mastitis tubes, and the use of stem growth
      regulators in grain production. The use of prophylactic measures (such as control
      of parasites or vaccination of calves against respiratory disease) was positively
      associated with BNP with an odds ratio of 14.3 as well as the use of
      PregSure((r)) BVD vaccine with an odds ratio of 426 (95% CI: 20-9095).

PMID- 22386741
TI  - Fourteen years in resistance.
AB  - Resistance trends have changed greatly over the 14 years (1997-2011) whilst I was
      Director of the UK Antibiotic Resistance Monitoring and Reference Laboratory
      (ARMRL). Meticillin-resistant Staphylococcus aureus (MRSA) first rose, then fell
      with improved infection control, although with the decline of one major clone
      beginning before these improvements. Resistant pneumococci too have declined
      following conjugate vaccine deployment. If the situation against Gram-positive
      pathogens has improved, that against Gram-negatives has worsened, with the spread
      of (i) quinolone- and cephalosporin-resistant Enterobacteriaceae, (ii)
      Acinetobacter with OXA carbapenemases, (iii) Enterobacteriaceae with
      biochemically diverse carbapenemases and (iv) gonococci resistant to
      fluoroquinolones and, latterly, cefixime. Laboratory, clinical and commercial
      aspects have also changed. Susceptibility testing is more standardised, with
      pharmacodynamic breakpoints. Treatments regimens are more driven by guidelines.
      The industry has fewer big profitable companies and more small companies without
      sales income. There is good and bad here. The quality of routine susceptibility
      testing has improved, but its speed has not. Pharmacodynamics adds science, but
      over-optimism has led to poor dose selection in several trials. Guidelines
      discourage poor therapy but concentrate selection onto a diminishing range of
      antibiotics, threatening their utility. Small companies are more nimble, but less
      resilient. Last, more than anything, the world has changed, with the rise of
      India and China, which account for 33% of the world's population and increasingly
      provide sophisticated health care, but also have huge resistance problems. These
      shifts present huge challenges for the future of chemotherapy and for the edifice
      of modern medicine that depends upon it.

PMID- 22386742
TI  - Augmented renal clearance in septic patients and implications for vancomycin
      optimisation.
AB  - The aim of this study was to evaluate the effect of augmented renal clearance
      (ARC) on vancomycin serum concentrations in critically ill patients. This
      prospective, single-centre, observational, cohort study included 93 consecutive,
      critically ill septic patients who started treatment that included vancomycin by
      continuous infusion, admitted over a 2-year period (March 2006 to February 2008).
      ARC was defined as 24-h creatinine clearance (CL(Cr))>130 mL/min/1.73 m(2). Two
      groups were analysed: Group A, 56 patients with a CL(Cr)<=130 mL/min/1.73 m(2);
      and Group B, 37 patients with a CL(Cr)>130 mL/min/1.73 m(2). Vancomycin
      therapeutic levels were assessed on the first 3 days of treatment (D(1), D(2) and
      D(3)). Serum vancomycin levels on D(1), D(2) and D(3), respectively, were 13.1,
      16.6 and 18.6 MUmol/L for Group A and 9.7, 11.7 and 13.8 MUmol/L for Group B
      (P<0.05 per day). The correlation between CL(Cr) and serum vancomycin on D(1) was
      -0.57 (P<0.001). ARC was strongly associated with subtherapeutic vancomycin serum
      concentrations on the first 3 days of treatment.

PMID- 22386743
TI  - Comparative in vitro activity of carbapenems against major Gram-negative
      pathogens: results of Asia-Pacific surveillance from the COMPACT II study.
AB  - Resistance rates amongst Gram-negative pathogens are increasing in the Asia
      Pacific region. The Comparative Activity of Carbapenem Testing (COMPACT) II study
      surveyed the carbapenem susceptibility and minimum inhibitory concentrations
      (MICs) of doripenem, imipenem and meropenem against 1260 major Gram-negative
      pathogens isolated from hospitalised patients at 20 centres in five Asia-Pacific
      countries (New Zealand, the Philippines, Singapore, Thailand and Vietnam) during
      2010. Pseudomonas aeruginosa (n=625), Enterobacteriaceae (n=500), and other Gram
      negative pathogens including Acinetobacter baumannii (n=135) were collected from
      patients with bloodstream infection (32.2%), nosocomial pneumonia including
      ventilator-associated pneumonia (58.1%), and complicated intra-abdominal
      infection (9.7%), with 36.7% being isolated from patients in an Intensive Care
      Unit. As high as 29.8% of P. aeruginosa and 73.0% of A. baumannii isolates were
      not susceptible to at least a carbapenem, whereas the majority of
      Enterobacteriaceae (97.2%) were susceptible to all carbapenems. Respective
      MIC(50)/MIC(90) values (MICs for 50% and 90% of the organisms, respectively) of
      doripenem, imipenem and meropenem were: 0.38/8, 1.5/32 and 0.38/16 mg/L for P.
      aeruginosa; 0.023/0.094, 0.25/0.5 and 0.032/0.094 mg/L for Enterobacteriaceae;
      and 32/64, 32/128 and 32/64 mg/L for A. baumannii. Doripenem and meropenem had
      comparable activity against P. aeruginosa, both being more active than imipenem.
      All carbapenems were highly potent against Enterobacteriaceae, although imipenem
      demonstrated higher MIC values than doripenem and meropenem. The three
      carbapenems showed less activity against A. baumannii. The high prevalence of
      carbapenem resistance amongst important nosocomial pathogens (P. aeruginosa and
      A. baumannii) warrants rigorous infection control measures and appropriate
      antimicrobial use in the Asia-Pacific region.

PMID- 22386744
TI  - Vaccination response following aerobic exercise: can a brisk walk enhance
      antibody response to pneumococcal and influenza vaccinations?
AB  - High intensity acute exercise at the time of vaccination has been shown to
      enhance the subsequent antibody response. This study examines whether an acute
      moderate intensity aerobic intervention prior to vaccination can enhance antibody
      response to pneumonia and half dose influenza vaccination. Sixty young (age
      (SD)=22.0 (6.1) years) and 60 older (age (SD)=57.5 (6.5) years) adults attended
      the laboratory on two separate occasions. At the first session, baseline antibody
      titres were determined, before participants completed either a brisk walk around
      campus at >55% of their age-predicted heart rate maximum, or a resting control
      condition, for 45 min. After the intervention, all participants received a full
      dose pneumococcal vaccination and a half-dose influenza vaccination. Four weeks
      later, participants returned for a follow up blood sample. Multivariate ANOVA
      revealed an increase in total antibody titres against the influenza vaccine
      (F((12,106))=25.76, p<.001, eta(2)=.75) and both the IgM (F((12,106))=17.10,
      p<.001, eta(2)=.66) and IgG (F((12,106))=25.76, p<.001, eta(2)=.75) antibody
      titres against the pneumococcal vaccine. However, there were no significant
      Time*Group interactions (p's all >.15), indicating that a 45 min brisk walk prior
      to vaccination did not affect antibody response to either the influenza or
      pneumonia vaccine. The results suggest that higher intensity exercise is
      necessary to augment antibody response to vaccination.

PMID- 22386745
TI  - Economic evaluation of vaccination programme of 7-valent pneumococcal conjugate
      vaccine to the birth cohort in Japan.
AB  - Aiming to introduce 7-valent pneumococcal conjugate vaccine (PVC-7) into routine
      vaccination schedule, the government of Japan gives a temporary budget to
      encourage municipalities in launching public vaccination programme which started
      on November 26, 2010 and ends on March 31, 2012. This study aims to appraise the
      'value for money' of PCV-7 vaccination programme from the societal perspective
      and the budget impact from the perspective of municipalities, which is
      responsible for providing routine vaccination. We conducted a cost-effectiveness
      analysis with Markov modelling and calculated incremental cost-effectiveness
      ratio (ICER) value of launching such programme with two levels of co-payment,
      Y1000 (US$13) or Y0, and two scenarios of the uptake of vaccine (vaccinated-alone
      or co-vaccinated with other vaccines). We found that when vaccinated-alone, ICERs
      in QALY were Y7,441,000 (US$93,013) or Y9,065,000 (US$113,313), and when co
      vaccinated Y7,441,000 (US$93,013) or Y5,489,000 (US$68,613), without or with
      productivity loss, respectively, regardless of co-payment level of the programme.
      Co-vaccinated programmes had lower ICER than vaccinated-alone programmes due to
      the savings in productivity loss. By adopting WHO's classification that an
      intervention is 'cost-effective' if ICER (in QALY) is between 1 and 3 times of
      GDP as a criterion, PCV-7 vaccination programme in Japan is concluded as "cost
      effective" from the perspective of society. The introduction of either no co
      payment or Y1000 (US$13) co-payment vaccination programme appears to be not
      budget saving for the first 6 years, whereas the level of budget impact are less
      than Y11,000,000 (US$137,500) or Y8,500,000 (US$106,250), respectively, for a
      municipality with 1000 birth cohort in the 1st year and 2nd to 5th year birth
      cohort proportional to the birth cohort population of estimated future
      population.

PMID- 22386746
TI  - A postmarketing evaluation of the safety of Ann Arbor strain live attenuated
      influenza vaccine in children 5 through 17 years of age.
AB  - BACKGROUND: Live attenuated influenza vaccine (LAIV) was licensed in 2003 in the
      United States for use in individuals aged 5-49 years. METHODS: A prospective
      observational postmarketing study was conducted to evaluate the safety of LAIV.
      Rates of medically attended events (MAEs) and serious adverse events (SAEs) in
      eligible children aged 5-17 years receiving LAIV as part of routine care from
      October 2003 to March 2008 were compared with rates in nonrandomized self,
      matched unvaccinated, and matched trivalent inactivated influenza vaccine (TIV)
      vaccinated controls. All MAEs and SAEs through 42 days postvaccination and all
      hospitalizations and deaths through 6 months postvaccination were analyzed.
      Statistical significance was assigned without multiplicity adjustment. RESULTS:
      43,702 LAIV recipients were matched with similar numbers of TIV-vaccinated and
      unvaccinated children. Of approximately 9500 MAE incidence rate comparisons, 204
      were statistically significantly higher and 168 were statistically significantly
      lower in LAIV recipients versus controls. No pattern of MAE rate differences
      suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically
      increased in LAIV recipients. No anaphylaxis events occurred within 3 days
      postvaccination. Rates of SAEs were similar between LAIV and control groups. Two
      SAEs were considered possibly related to LAIV: Bell's palsy and nonspecific
      paroxysmal spell. CONCLUSIONS: Results of this postlicensure evaluation of LAIV
      safety in US children aged 5-17 years are consistent with preapproval clinical
      studies and Vaccine Adverse Event Reporting System reports, both of which
      demonstrated no significant increase in asthma/wheezing events or other adverse
      outcomes among eligible children who received LAIV.

PMID- 22386747
TI  - Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune
      response to unrelated antigens.
AB  - The HIV-1 Tat protein is able to raise a humoral immune response in the absence
      of adjuvant. Here, we investigated whether this property can be transferred to
      unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell
      dependent phenomenon in which a Th2 profile predominates. Then, we showed that
      the determinant governing the property is located in the region 1-57 of Tat and
      that fragment Tat1-57 can make two unrelated model antigens immunogenic in the
      absence of adjuvant. We found a Th2 pattern of immune response for both antigens,
      suggesting that Tat1-57 mediates this response. Next, we showed that, although
      less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the
      adjuvant property to other antigens. We also observed that preservation of
      cysteine 37 is absolutely required for the transfer, suggesting the role of
      disulphide-mediated dimerization in the transfer of the adjuvant property. Our
      observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or
      Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby
      opening up new perspectives in vaccination.

PMID- 22386748
TI  - CD4+ T-cell activation for immunotherapy of malignancies using Ii-Key/MHC class
      II epitope hybrid vaccines.
AB  - Active immunotherapy is becoming a reality in the treatment of malignancies.
      Peptide-based vaccines represent a simple, safe, and economic basis for cancer
      immunotherapeutics development. However, therapeutic efficacy has been
      disappointing. Some of the reasons for this, such as selection of patients with
      advanced disease and ignorance of the delayed activity of many immunotherapeutic
      vaccines, have hampered the entire field of cancer immunotherapy over the last
      decade. Another reason for this may be that most peptide regimens historically
      have focused on activation of CD8+ cytotoxic T lymphocytes, having little or only
      indirect CD4+ T helper (Th) cell activation. We review here evidence for the
      importance of specific CD4+ Th activation in cancer immunotherapy and the use of
      Ii-Key technology to accomplish this. Ii-Key (LRMK), a portion of the MHC class
      II-associated invariant chain (Ii protein), facilitates the direct charging of
      peptide epitopes onto MHC class II molecules. Directly linking Ii-Key to MHC
      class II peptide epitopes greatly enhances their potency in activating CD4+ T
      cells. The Ii-Key hybrid AE37, generated by linking LRMK to the known HER2 MHC
      class II epitope HER2 (aa 776-790), has been shown to generate robust, long
      lasting HER2-specific immune responses both in patients with breast and prostate
      cancer. Interim data from a phase II study of AE37 in breast cancer patients
      suggest a possible improvement in clinical outcome. The Ii-Key hybrid technology
      is compared to other methods for enhancing the potency of peptide immunotherapy
      for cancer.

PMID- 22386749
TI  - Characterization of a new insect cell line that is derived from the neonate
      larvae of Papilio xuthus (Lepidoptera: Papilionidae) and its susceptibility to
      AcNPV.
AB  - The cell line RIRI-PX1 was established from neonate larval tissues of Papilio
      xuthus by performing primary cultures in the modified Grace medium that was
      supplemented with 20% fetal bovine serum (FBS). The cell line primarily consisted
      of spindle-shaped and spherical cells which attached themselves to the flask. The
      population-doubling times (PDTs) at the 50th and 60th passage were 42.5 h and
      42.1 h respectively. The average chromosome numbers of RIRI-PX1 cell line from
      passage 5 to passage 50 ranged from 103 to 199. It was confirmed that RIRI-PX1
      cell line was derived from P. xuthus by comparing the mitochondrial cytochrome c
      oxidase subunit I gene (COI) of RIRI-PX1 cells and P. xuthus eggs. This cell line
      was susceptible to the Autographa californica nucleopolyhedrovirus (AcNPV) and
      produced high yield of polyhedral occlusion bodies (43.9OBs/cell) after 10 days
      of infection by AcNPV. The virus titer of AcNPV infected RIRI-PX1 cells was
      3.25*107 TCID50/ml. We concluded that the RIRI-PX1 cell line is established from
      the neonate larvae tissues successfully and the cells of the cell line are
      sensitive to AcNPV.

PMID- 22386750
TI  - Axillary management in breast cancer: what's new for 2012?
AB  - Sentinel lymph node (SLN) biopsy has become standard care for management of the
      axilla in invasive breast cancer, replacing axillary lymph node dissection (ALND)
      in most subjects, with a progressively diminishing role of ALND. Advances in
      preoperative imaging have also changed the algorithm for axillary management, and
      ultrasound-guided needle biopsy has been shown to triage >50% of subjects with
      node metastases to ALND. However, the past two years have witnessed remarkable
      and practice-changing advances in our knowledge and approach to management of the
      axilla, with availability of high-level evidence that demands reappraisal of
      practice and challenges the role of routine ALND for SLN-positive patients. In
      particular, for the group of patients defined by eligibility criteria in the
      Z0011 trial, it appears that ALND has little or no effect on local recurrence and
      survival, or on the choice of local or systemic therapies. We review the
      available evidence on staging and management of the axilla in breast cancer, and
      outline our interpretation of its implications for clinical practice.

PMID- 22386751
TI  - Allele frequencies of 15 STR loci using AmpF/STR Identifiler kit in the Maldivian
      population.

PMID- 22386752
TI  - Functional outcomes and complications in patients with bladder cancer undergoing
      robotic-assisted radical cystectomy with extracorporeal Indiana pouch continent
      cutaneous urinary diversion.
AB  - OBJECTIVE: To evaluate the functional outcomes and complications for patients
      with bladder cancer undergoing robotic-assisted laparoscopic radical cystectomy
      with Indiana pouch continent cutaneous urinary diversion. METHODS: From February
      2004 to March 2010, 34 patients underwent robotic-assisted laparoscopic radical
      cystectomy with Indiana pouch continent cutaneous urinary diversion
      reconstruction. After surgery, the complications were identified, categorized,
      and graded using an established 5-grade modification of the original Clavien
      grading system, and continence was assessed. Descriptive statistics were used in
      evaluating the outcomes. Fischer's exact test was used in the comparison of early
      and late Clavien grade III complications. RESULTS: Overall, 175 (123 early and 52
      late) complications after surgery were reported in 32 (94%) of 34 patients.
      Within 90 days of surgery, 31 (91%) of 34 patients experienced >= 1 early
      complication. Of 34 patients, 15 (44%) reported >= 1 late complications (>90
      days). Most (85% and 69%, respectively) early and late complications were graded
      as minor (grade II or less). Fewer patients with early complications required an
      additional intervention (grade III) compared with patients with late
      complications (14% vs 31%; P = .116). The most common complication in both
      intervals was infection, reported in 22% and 37% of patients with early and late
      complications, respectively. The continence data for 31 patients at a mean follow
      up of 20.1 months (median 12.0) showed that all but 1 patient (97%) had daytime
      and nighttime continence. CONCLUSION: Patients undergoing robotic-assisted
      laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary
      diversion reconstruction have comparable complication rates and functional
      outcomes compared with patients in the open series.

PMID- 22386753
TI  - Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of
      bladder afferent pathways in spinal cord injured rats.
AB  - OBJECTIVE: To evaluate the role of M2 and M3 muscarinic acetylcholine receptor
      (mAChR) subtypes in the activation of bladder afferent pathways in rats with
      chronic spinal cord injury (SCI). METHODS: Adult female Sprague-Dawley rats were
      spinalized at the T9 level. Continuous cystometry was performed under awake
      conditions 2 or 4 weeks after SCI. The effects of intravesical administration of
      an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine),
      an M2-selective antagonist (methoctramine), and an M3-selective antagonist
      (darifenacin) were examined. After cystometry, the bladder was removed and
      separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression
      in the mucosa was determined using real-time quantitative polymerase chain
      reaction. RESULTS: At 2 and 4 weeks after SCI, intravesical administration of a
      nonselective mAChR agonist (25 MUM oxotremorine-methiodide) increased the area
      under the curve of nonvoiding contractions, although the intercontraction
      interval of voiding contractions and maximal voiding pressure did not change.
      This effect was blocked by atropine and methoctramine (10 MUM) but not by
      darifenacin (50 MUM). However, mAChR antagonists alone (10-50 MUM) had no effect
      on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa
      of SCI rats compared with that in normal rats. CONCLUSION: Our results suggest
      that the M2 mAChR subtype plays an important role in bladder afferent activation
      that enhances detrusor overactivity in SCI rats. However, because mAChR
      antagonists alone did not affect any cystometric parameters, the muscarinic
      mechanism controlling bladder afferent activity might not be involved in the
      emergence of detrusor overactivity in SCI.

PMID- 22386754
TI  - Pyourachus in spina bifida: case report and review.
AB  - Failure of the urachus to close results in a multitude of clinical anomalies.
      Such anomalies have been documented as occurring in association with mechanical
      bladder outlet obstruction. However, no urachal anomalies have been linked
      specifically to spina bifida. Two cases of urachal abscesses were identified in
      adolescent male patients with spina bifida at our institution, both with
      neuropathic bladders and using self-catheterization. The clinical presentations
      differed, with classic involvement of the umbilicus in 1 case. Because of its
      varied presentations, the diagnosis of a urachal anomaly is potentially
      difficult. Urachal anomalies should be considered in the evaluation of pelvic
      masses in this demographic.

PMID- 22386755
TI  - Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as
      urinary biomarkers for bladder cancer detection.
AB  - OBJECTIVE: To investigate whether elevated urinary levels of vascular endothelial
      growth factor (VEGF), carbonic anhydrase 9 (CA9), and angiogenin are associated
      with bladder cancer (BCa). METHODS: This was a case-control study in which voided
      urine samples from 127 patients (63 control subjects and 64 patients with BCa)
      were analyzed. The urinary concentrations of VEGF, CA9, angiogenin, and bladder
      tumor antigen (BTA) were assessed using enzyme-linked immunosorbent assays. We
      used the area under the curve of receiver operating characteristic curves to
      determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine
      samples. Data were also compared with the findings from a commercial enzyme
      linked immunosorbent assay-based BCa detection assay (BTA-Trak). The sensitivity,
      specificity, and positive and negative predictive values were calculated.
      RESULTS: The urinary concentrations of VEGF, CA9, angiogenin, and BTA were
      significantly elevated in those with BCa. VEGF was the most accurate urinary
      biomarker (area under the curve 0.886, 95% confidence interval 0.8301-0.9418).
      Furthermore, multivariate regression analysis highlighted VEGF (odds ratio 5.90,
      95% confidence interval 2.60-13.40, P < .0001) as an independent variable. The
      sensitivity and specificity for VEGF (83% sensitivity and 87% specificity)
      outperformed those for BTA (80% sensitivity and 84% specificity). CONCLUSION:
      VEGF could be a valuable addition to voided urine sample analysis for the
      detection of BCa. Larger, prospective studies are needed to determine the
      clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive
      evaluation of patients with BCa.

PMID- 22386756
TI  - Caliceal-cutaneous fistula after kidney transplantation.
AB  - Urinary fistula is a one of the most common complications after kidney
      transplantation. Conservative treatment with stent and Foley catheter drainage
      may be tried, however in some cases more invasive approach is needed. Caliceal
      fistula is a rare condition and the diagnosis may be missed. Here we present an
      interesting case of caliceal-cutaneous fistula diagnosed by computed tomography
      after living kidney transplantation. After failure of conservative management,
      the patient was successfully treated with partial nephrectomy.

PMID- 22386757
TI  - [Immune reconstitution syndrome in a case of disseminated tuberculosis after
      withdrawal of treatment with adalimumab].

PMID- 22386758
TI  - [Nocardia nova as cause of right sided pectoralis pyomyositis identified by mass
      spectrometry].

PMID- 22386759
TI  - [Impact of delayed discharge for nonmedical reasons in a tertiary hospital
      internal medicine department].
AB  - BACKGROUND: Delayed discharge occurs from a clinical point of view when a patient
      is considered medically fit for discharge but continues occupying a bed due to a
      nonmedical problem. This circumstance overloads the care system, however, its
      real frequency and loss of useful days of hospitalization have not being
      evaluated in Spain up to date. OBJECTIVE: To analyze the frequency of hospital
      delayed discharges due to non-medical reasons in a tertiary hospital Internal
      Medicine Department and to determine the clinical and socio-familial factors
      related to this situation. PATIENTS AND METHODS: An observational and prospective
      study was performed to analyze the characteristics of the patients whose
      discharge was delayed for nonmedical reason over a 12-month period. RESULTS:
      There were 4850 discharges in the Internal Medicine Department, 170 (3.5%) of
      which were delayed because of nonmedical problems. This accounted for a loss of
      1603 useful days of hospitalization for other patients within one year. The
      median delay was 5 days (range: 3-12). Patients with delayed discharges were
      elder and had a higher prevalence of acute cerebrovascular disease as well as
      alcohol or benzodiazepines use related problems. The main causes were the
      overload or inability of the family to care for the patient and the impossibility
      to combine patient care with the family's working life (51.8%), and lack of
      family or social support network (21.8%). CONCLUSIONS: Delayed discharges for
      nonmedical reasons are frequent and mainly motivated by social-familiar problem
      to take charge of the patients after their hospitalization. This accounts for a
      significant overload for the hospitals.

PMID- 22386760
TI  - Oxidative stress-induced autophagy in plants: the role of mitochondria.
AB  - The strictly regulated removal of oxidized structures is a universal stress
      response of eukaryotic cells that targets damaged or toxic components for
      vacuolar or lysosomal degradation. Autophagy stands at the crossroad between cell
      survival and death. It promotes survival by degrading proteins and organelles
      damaged during oxidative stress, but it is also activated as a part of death
      programs, when the damage cannot be overcome. Evidence is accumulating that the
      cellular sites of ROS production and signaling may be primary targets of
      autophagy. Therefore, autophagosomal targeting of mitochondria (mitophagy) is of
      particular importance. Mitophagy is a selective process that can specifically
      target dysfunctional mitochondria, but also mitophagy may play a role in
      controlling the number and quality of mitochondria during stress. Here we review
      the mechanisms of both non-specific autophagy and mitochondrial targeting in
      plants, drawing analogies and emphasizing differences with yeast and mammalian
      systems.

PMID- 22386761
TI  - The other rabies viruses: The emergence and importance of lyssaviruses from bats
      and other vertebrates.
AB  - The recognition that viruses related to rabies virus cause rabies in humans has
      stimulated research into the relationships, geographic distribution and natural
      histories of these viruses. This paper reviews what is known of these fascinating
      viruses and the complexity of prevention and treatment of the disease they cause.

PMID- 22386762
TI  - Accumulation of oocytes: a new strategy for managing low-responder patients.
AB  - Accumulation of oocytes from several ovarian stimulation cycles is currently
      possible using novel vitrification technologies. This strategy could increase the
      inseminated cohort, creating a similar situation to normoresponders. This study
      included 242 low-responder (LR) patients (594 cycles) whose mature oocytes were
      accumulated by vitrification and inseminated simultaneously (LR-Accu-Vit) and 482
      patients (588 cycles) undergoing IVF/embryo transfer with fresh oocytes in each
      stimulation cycle (LR-fresh). Drop-out rate in the LR-fresh group was >75%. The
      embryo-transfer cancellation per patient was significantly lower in the LR-Accu
      Vit group (9.1%) than the LR-fresh group (34.0%). Live-birth rate (LBR)/patient
      was higher in the LR-Accu-Vit group (30.2%) than the LR-fresh group (22.4%).
      Cumulative LBR/patient was statistically higher in the LR-Accu-Vit group (36.4%)
      than the LR-fresh group (23.7%) and a similar outcome was observed among patients
      aged ?40years (LR-Accu-Vit 15.8% versus LR-fresh 7.1%). The LR-Accu-Vit group had
      more cycles with embryo cryopreservation (LR-Accu-Vit 28.9% versus LR-fresh
      8.7%). Accumulation of oocytes by vitrification and simultaneous insemination
      represents a successful alternative for LR patients, yielding comparable success
      rates to those in normoresponders and avoiding adverse effects of a low response.
      The accumulation of oocytes from several ovarian stimulation cycles is currently
      possible with the aid of novel vitrification technologies. This strategy could be
      useful for low-responder patients, contributing to increase the inseminated
      cohort and creating a similar situation as in normal responders. According to the
      results presented herein (higher live-birth rate per patient treated), this
      strategy represents a successful alternative for low-responder patients, yielding
      comparable success rates to those in normal responders and avoiding the adverse
      effects of a low response.

PMID- 22386763
TI  - Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene
      citrate in oxidative metabolism.
AB  - This study investigated the in-vitro antioxidant properties of the ovulation
      induction drug, clomiphene citrate, and assessed whether its effects are
      influenced by the Val16Ala polymorphism in the SOD2 gene, which encodes manganese
      superoxide dismutase enzyme. The investigation involved an in-vitro experimental
      protocol testing the effect of different concentrations of clomiphene citrate on
      antioxidant capacity, reactive oxygen species (ROS) production and peripheral
      blood mononuclear cell (PBMC) culture viability. A total of 58 healthy adult
      women were genotyped for the Val16Ala SOD2 polymorphism, and blood samples were
      collected to perform in-vitro experiments. ROS production and cytotoxicity assays
      were performed on blood and PBMC from carriers of different Val16Ala SOD2
      genotypes. Clomiphene citrate exhibited antioxidant capacity and effects and
      decreased ROS production. The AA genotype displayed a more responsive antioxidant
      effect with clomiphene citrate treatment than other genotypes. AA and AV PBMC
      showed an increase in viability following treatment with 10 MUmol/l clomiphene
      citrate when compared with control groups. The results suggest that clomiphene
      citrate exhibits antioxidant activity similar to that observed with other
      selective oestrogen receptor modulators, and the intensity of the effect appears
      to be SOD2 polymorphism dependent. This study was performed to investigate
      whether clomiphene citrate, a drug broadly used to evaluate reproductive function
      in women, presents antioxidant effects and if these effects could be influenced
      by genetic variation in the women. We found evidence that clomiphene citrate has
      some antioxidant properties similar to those observed with other selective
      oestrogen receptor modulators such as tamoxifen. As the antioxidant enzyme
      manganese superoxide dismutase (SOD2) is considered a key molecule involved in
      female reproductive metabolism, we also tested if a functional SOD2 gene
      polymorphism (Val16Ala) could influence the in-vitro antioxidant clomiphene
      citrate response. Significant differences of the clomiphene citrate antioxidant
      effect on PBMC with different Val16Ala SOD genotypes were observed in this study.
      Based on these results, we could speculate that alterations in SOD2 activity
      caused by the Val16Ala polymorphism can result in differential responses to drugs
      such as clomiphene citrate. In assisted reproduction clinics, clomiphene citrate
      is commonly used to induce ovulation, especially in patients with polycystic
      ovary syndrome. However, some women have clomiphene citrate resistance and either
      ovulation is not triggered by the drug or ovulation is induced but the pregnancy
      still fails. The causes of no effect of clomiphene citrate remain unclear and we
      cannot discard the influence of genetic effects including the Val16Ala SOD2
      polymorphism. Therefore, it is important to perform complementary investigations
      considering the potential pharmacogenetic influence of Val16Ala SOD2 polymorphism
      on the treatment of polycystic ovary syndrome or in ovulation to elucidate this
      question.

PMID- 22386764
TI  - Atomic force microscopy: a powerful tool for studying bacterial swarming
      motility.
AB  - Swarming motility is a fascinating phenomenon by which some bacteria use flagella
      to move over solid surfaces. Understanding the molecular mechanisms underlying
      swarming motility requires studying the factors that induce and control flagella
      expression in swarming cells. Traditionally, flagella are observed by optical or
      electron microscopy, but none of these techniques combine versatility and
      easiness, with quantitative and high-resolution information. We report an atomic
      force microscopy (AFM)-based approach for the fast imaging of bacterial
      phenotypes (cell shape, flagella expression) in swarming motility studies. Cells
      from the gram-positive bacterium Bacillus thuringiensis sv. israelensis were
      inoculated on energy-rich media containing increasing agar concentrations.
      Following swarming assays (2 days), the cell morphology and the amount of
      flagella were directly observed by AFM imaging in air. Consistent with the
      macroscopic swarming behavior, cells harvested from the rim of colonies spreading
      on soft agar were hyperflagellated, elongated and arranged in chains. Increasing
      the agar concentration led to much lower amounts of flagella and to shorter rod
      shaped cells, a finding consistent with the slower swarming motility of the
      cells. Cells taken from colony centers on soft and hard agar surfaces were
      generally non-flagellated, rod-shaped, rarely arranged in chains, and exhibited
      lysis and sporulation. This study shows that AFM imaging can readily discriminate
      between swarming and non-swarming cells, and quantify their morphological
      details, thus offering an important tool to study the dynamics of bacterial
      populations.

PMID- 22386765
TI  - Video-frequency scanning transmission electron microscopy of moving gold
      nanoparticles in liquid.
AB  - Immobilized gold nanoparticles were imaged in a liquid containing water and 50%
      glycerol with scanning transmission electron microscopy (STEM). The specimen was
      enclosed in a liquid compartment formed by two silicon microchips with electron
      transparent windows. A series of images was recorded at video frequency with a
      spatial resolution of 1.5nm. The nanoparticles detached from their support after
      imaging them for several seconds at a magnification of 250,000. Their movement
      was found to be much different than the movement of nanoparticles moving freely
      in liquid as described by Brownian Motion. The direction of motion was not random
      the nanoparticles moved either in a preferred direction, or radially outwards
      from the center of the image. The displacement of the gold nanoparticles over
      time was three orders of magnitude smaller than expected on the basis of Brownian
      Motion. This finding implies that nanoscale objects of flexible structure or
      freely floating, including nanoparticles and biological objects, can be imaged
      with nanoscale resolution, as long as they are in close proximity to a solid
      support structure.

PMID- 22386766
TI  - Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and
      oxidative stress.
AB  - BACKGROUND: Over 6 million people die annually in the world because of cancer.
      Several groups are focused on studying cancer chemoprevention approaches.
      Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and
      chemopreventive. However, it has a dose-dependent effect on cell death, even on
      some cancer cells. OBJECTIVES: Our aim was to investigate this dose-dependent
      effect on human bladder carcinoma ECV304 cells during oxidative stress condition.
      METHODS: For this purpose, ECV304 cells incubated with different Resveratrol
      concentrations were analyzed as for their metabolic rate, membrane permeability,
      DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine
      exposure after oxidative stress. RESULTS: Resveratrol induced cell death at high
      concentrations (>20 MUM), but not at low ones (0.1-20 MUM). Pretreatment with 2.5
      MUM protected the cells from oxidative damage, whereas 50 MUM intensified the
      cell death and significantly increased Bad/Bcl-2 ratio
      (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and
      PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA
      activated ECV304 cells. CONCLUSIONS: Resveratrol at high doses induces cell death
      of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein
      induced by Resveratrol could be mediating this effect. This information about the
      role of Resveratrol on cancer alerts us about its dose-dependent effects and
      could lead the design of future chemoprevention strategies.

PMID- 22386767
TI  - Life satisfaction, loneliness and related factors during female midlife.
AB  - BACKGROUND: Studies assessing life satisfaction and feelings of loneliness in mid
      aged women are scarce. OBJECTIVE: To assess loneliness, life satisfaction and
      related factors in mid-aged Spanish women. METHOD: This was a cross sectional
      study in which 182 women aged 40 to 65 completed the menopause rating scale
      (MRS), the University of California at Los Angeles loneliness scale (UCLA-LS),
      the life satisfaction index A (LSI-A), and a general socio-demographic
      questionnaire containing personal/partner data. Internal consistency of each tool
      was also computed. RESULTS: Median [interquartile range] age of the sample was 51
      [9.0] years. A 55.5% were postmenopausal, 47.3% had increased body mass index
      (BMI) values, 57.7% were abdominally obese, 1.6% had hypertension and 86.3% had a
      stable partner. In addition, 4.9% used hormone therapy and 19.2% psychotropic
      drugs. Multiple linear regression analysis found that higher UCLA-LS scores (more
      loneliness) correlated with MRS psychological scores, partner alcohol abuse,
      living in urban areas, lower LSI-A scores (less life satisfaction) and not having
      a stable partner. Lower LSI-A scores (worse life satisfaction) correlated with
      severe female economical problems, BMI values and UCLA-LS and MRS psychological
      scores. CONCLUSION: Loneliness and life satisfaction in this mid-aged female
      sample was influenced by personal and partner issues which seem to play a much
      more relevant role than biological aspects. More research is warranted in this
      regard.

PMID- 22386768
TI  - Esophageal body motility in people with diabetes: comparison with non-diabetic
      healthy individuals.
AB  - AIMS: The aim of this study was to compare esophageal motor characteristics
      between diabetics and healthy individuals. METHODS: Esophageal manometry was
      performed in 34 type 2 diabetics and 32 healthy individuals. Waves were evaluated
      in the 3 thirds of the esophagus (P1=upper, P2=middle, and P3=distal). RESULTS:
      In diabetics vs. controls, wave distribution was as follows: peristaltic waves,
      83.5 +/- 22.2% vs. 96.3 +/- 4.4%, p<0.002; simultaneous waves, 3.26 +/- 5.8% vs.
      0.53 +/- 1.3%, p<0.01; no transmitted waves, 10.62 +/- 20.7% vs. 2.75 +/- 3.0%,
      p<0.002; and retrograde waves, 2.68 +/- 4.0% vs. 0.31 +/- 1.1%, p<0.03. Wave
      amplitude was similar between groups. Average upstroke (mmHg/s) in diabetics vs.
      non-diabetics was P2, 33.8 +/- 13.9 vs. 40.2 +/- 17.7, p<0.03; and P3, 29.8 +/-
      15.3 vs. 41.3 +/- 14.0, p<0.002. CONCLUSIONS: (1) Simultaneous waves, no
      transmitted waves, and retrograde esophageal waves were significantly more
      frequent in diabetics. (2) Average upstroke was significantly lower within the
      middle and distal esophagus of diabetic individuals. (3) Wave amplitude was
      similar in both groups.

PMID- 22386769
TI  - Relation between diabetes, metformin treatment and the occurrence of malignancies
      in a Belgian primary care setting.
AB  - BACKGROUND: Associations between type 2 diabetic patients and a higher risk of
      developing cancer have been reported worldwide. Recently, a protective effect of
      metformin has been described. AIM: To examine in the Belgian primary care
      population the relation between presence of type 2 diabetes with and without
      metformin treatment and the occurrence of malignancies. DESIGN OF STUDY:
      Retrospective cohort study, based on the Intego database, an ongoing Belgian
      general practice-based morbidity registry, covering 90 general practitioners and
      including about 1.5 million patient-years between 1994 and 2008. METHOD: Cox
      proportional hazard analysis comparing emergence of malignancy in patients with
      and without type 2 diabetes, and among patients with diabetes comparing emergence
      of malignancy in those treated with various antidiabetic drugs. RESULTS:
      Malignancies occurred more in type 2 diabetic patients compared to non-diabetic
      controls (HR=1.84; 95% CI=1.51-2.24), adjusted for age, gender and weight.
      Treatment with both metformin and 'other' antidiabetic agents was related to
      decreased cancer risk (HR=0.24 and 0.22) compared to diet only in men but not in
      women. CONCLUSION: In this Belgian primary care setting, diabetic patients have
      higher cancer prevalences than non-diabetic patients. Moreover, in diabetic men,
      not only metformin but also other antidiabetic agents were associated with lower
      cancer risks.

PMID- 22386770
TI  - The American Journal of Pathology Centennial Project: celebrating 100 years of
      the American Society for Investigative Pathology.

PMID- 22386771
TI  - Population genomics: an investigative tool for epidemics.

PMID- 22386772
TI  - Clinical response to antipsychotic drug treatment: association study of
      polymorphisms in six candidate genes.
AB  - Pharmacogenetic studies have demonstrated significant associations between
      several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and
      antipsychotic drug response. The present study investigates the effect of nine
      polymorphisms in these genes for an association with antipsychotic treatment
      response. 329 Caucasian patients with a non-affective psychotic disorder using
      antipsychotics were included. All patients participated in the longitudinal GROUP
      study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: TaqI_A,
      -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT:
      Val158Met; MTHFR: 677-C/T) using standard protocols. Polymorphisms were based on
      previous studies showing associations with positive symptoms treatment response.
      The Clinical Global Impression - Improvement (CGI-I) scale was used to assess
      improvement in positive psychotic symptoms since the start of current
      antipsychotic treatment. Ordinal regression was used for association analyses.
      Ninety percent of the patients used second generation antipsychotics, with
      olanzapine (28%) and risperidone (29%) being the most prescribed drugs. Ser9Gly
      of the dopamine D3 receptor gene (P value 0.034) and 677-C/T of MTHFR (P value
      0.019) were tested statistically significant. Gly-carriers and T-carriers,
      respectively, showed more clinical improvement on the CGI-I. The other
      polymorphisms did not show a statistically significant association (P
      values>0.10). In conclusion, we replicated two out of nine of the previously
      reported associations between polymorphisms and treatment response. The direction
      and magnitude of the associations presented here in DRD3 (Ser9Gly) and MTHFR (677
      C/T) are in line with previous association studies in Caucasian patients. These
      polymorphisms may be of value for predicting clinical response.

PMID- 22386773
TI  - Equipercentile linking of the Brief Psychiatric Rating Scale and the Clinical
      Global Impression Scale in a catchment area.
AB  - Recent analyses tried to explain the meaning of the Brief Psychiatric Rating
      Scale total score (BPRS) and its percentage change from baseline by
      equipercentile linking with the Clinical Global Impression Scale (CGI). A major
      limitation was that they were conducted in clinical trial populations limiting
      generalisability to 'real-world' patients. We therefore replicated the findings
      in a large sample covering patients admitted to a state hospital with a catchment
      area. BPRS and CGI ratings at admission (n=1772) and at discharge from all
      patients with schizophrenic disorders (ICD-10 F20.0-F20.9) admitted between 2005
      and 2008 were compared using equipercentile linking. Being considered "mildly
      ill" according to the CGI severity score approximately corresponded to a BPRS
      total score of 25, "moderately ill" to a BPRS of 33-35, "markedly ill" to a BPRS
      of 50 and severely ill to a BPRS of 70. To be "minimally improved" according to
      the CGI change score was associated with a mean BPRS reduction of 13%; and "much
      improved" with 50% BPRS reduction. The linking functions were not identical, but
      overall comparable to those in previous randomised trial samples. The suggestion
      that a 50% BPRS reduction from baseline is a clinically meaningful definition of
      response in acutely ill patients was reinforced.

PMID- 22386774
TI  - Photo-corrosion inhibition and photoactivity enhancement with tailored zinc oxide
      thin films.
AB  - The nanocrystalline ZnO, TiO(2) and ZnO/TiO(2) films are deposited onto FTO
      coated glass substrates by using spray pyrolysis technique. The structural,
      morphological, optical and photoelectrochemical properties of the ZnO, TiO(2) and
      ZnO/TiO(2) are investigated by X-ray diffraction, scanning electron microscopy,
      UV-Vis spectroscopy and photoelectrochemical techniques. XRD analysis shows that
      films are polycrystalline and having hexagonal and tetragonal crystal structure
      for pure ZnO and TiO(2). The photocatalytic degradation of methylene blue has
      been investigated with ZnO, TiO(2) and ZnO/TiO(2) photocatalysts. ZnO/TiO(2) thin
      films have proved quite effective mineralization of methylene blue, while pure
      ZnO and TiO(2) do not lead complete mineralization of methylene blue. The
      metabolites produced during degradation are analyzed by HPLC and Fourier
      transforms infrared spectroscopy. The by-products detected during degradation
      have been identified by GCMS technique.

PMID- 22386775
TI  - Photophysics of DNA staining dye Propidium Iodide encapsulated in bio-mimetic
      micelle and genomic fish sperm DNA.
AB  - Photophysical processes in Propidium Iodide (PI), the well known DNA staining
      dye, have been exploited in homogeneous as well as heterogeneous medium by steady
      state and time resolved spectroscopy. The DNA staining dye PI exhibits
      intermolecular proton transfer reaction in aqueous and hydrogen-bonding acceptor
      solvents due to the formation of quinonoid structure which is acidic in nature.
      Time resolved emission spectroscopy also predicts the hydrogen bond donor ability
      of PI. The target dye interacts only with anionic surfactant sodium
      dodecylsulphate but not with cationic surfactant cetyltrimethylammonium bromide
      and neutral surfactant Triton X-100 and this interaction is found to be
      electrostatic in nature. We have further scrutinized the mode of binding of PI
      with fish sperm DNA. The effect of addition of urea, fluorescence quenching
      phenomenon, CD measurements reveal that the probe binds to DNA through
      intercalative style.

PMID- 22386776
TI  - Expansion of T-cells from the cord blood graft as a predictive tool for
      complications and outcome of cord blood transplantation.
AB  - We have previously successfully expanded functional T-cells in vitro from cord
      blood grafts used for clinical transplantation, with the aim of creating donor
      lymphocyte infusions to treat e.g. malignant relapse. Here we show that the T
      cell expansion in addition might work as a prognostic tool for complications
      after transplantation. We used multi-color flow cytometry to correlate in vitro
      phenotypical and functional data from 33 expansions to clinical outcome post
      transplantation. Higher levels of CD69+ activated T-cells in the expansion were
      associated with prolonged survival of the patient. In addition, we found a
      correlation between T-cell expansions containing relatively high levels of
      effector memory T-cells and graft vs. host disease and relapse. Our data suggest
      that expansions of cord blood T-cells from the graft might not only be used as
      donor lymphocyte infusions, but also as in vitro indicators that could give
      essential information on how to manage cord blood transplanted patients.

PMID- 22386777
TI  - The effect of prolonged fasting on levels of growth hormone-binding protein and
      free growth hormone.
AB  - OBJECTIVE: There are limited data on growth hormone-binding protein (GHBP) and
      free GH levels during the physiological challenge of a prolonged fast. Our aim
      was to explore the relationships between GHBP, free GH, total GH and non
      esterified fatty acid (NEFA) levels during overnight and 24-hour fasts in healthy
      young adults. DESIGN: We measured nocturnal levels of GHBP at three time-points
      (22:00, 03:00, 08:00), NEFA every 60 min and ultra-filtered free GH and total GH
      at 15-minute intervals for 10 h (22:00-08:00) during an overnight and a 24-hour
      fast in 7 female and 4 male normal-weight subjects aged 24.8 years (range: 22.8
      26.9) with BMI 22.5 kg/m2 (range: 18-27). RESULTS: Spontaneous free and total GH
      levels were closely related during the overnight and 24-hour fasts (r=0.99,
      p<0.0001 and r=0.99, p<0.0001 respectively). 24 h of fasting led to an increase
      in levels of basal free GH (p=0.03), mean free GH (p=0.04), mean total GH
      (p=0.04) and NEFA (p<0.0001) whilst GHBP levels remained similar (p=0.8).
      Percentage free (over total) GH was similar during the overnight and prolonged
      fasts (p=0.3). There were no associations between levels of NEFA and free
      (r=0.24, p=0.5) or total GH (r=0.20, p=0.6). CONCLUSIONS: A 24-hour fast led to
      parallel increases in free and total GH levels whilst there was no discernable
      change in GHBP levels or the fraction of free GH. This suggests that GHBP plays a
      role in limiting variations of circulating free GH levels. NEFA levels increased
      during the prolonged fast but they were not correlated with free or total GH
      levels.

PMID- 22386778
TI  - Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and
      postsynaptic serotonergic transmission.
AB  - Preclinical and clinical studies suggest that direct and indirect cannabinoid
      agonists, including enhancers of endocannabinoids, engender stress-relieving,
      anxiolytic and antidepressant effects, mediated by central CB(1) receptors
      (CB(1)Rs). The effect of the main pharmacologically active principle in cannabis,
      (-)-trans-Delta(9)-tetrahydrocannabinol (delta-9-THC), on depressive behavior and
      on the serotonin (5-HT) system, which is implicated in the mechanism of action of
      antidepressants, has not been extensively clarified. Here, we showed that
      repeated (5 days), but not single (acute) intraperitoneal (ip) treatment with
      delta-9-THC (1mg/kg) exerts antidepressant-like properties in the rat forced swim
      test (FST). This effect was CB(1)R-dependent because it was blocked by the CB(1)R
      antagonist rimonabant (1mg/kg, ip). Using in vivo electrophysiology, we
      demonstrated that delta-9-THC modulated dorsal raphe (DR) 5-HT neuronal activity
      through a CB(1)R-dependent mechanism. Acute intravenous delta-9-THC
      administration (0.1-1.5mg/kg) elicited a complex response profile, producing
      excitatory, inhibitory and inert responses of 5-HT neurons. Only excitatory
      responses were blocked by rimonabant. Finally, repeated but not single delta-9
      THC administration (1mg/kg, ip) enhanced tonic 5-HT(1A) receptor activity in the
      hippocampus, a postsynaptic event commonly elicited by standard antidepressants.
      These results suggest that delta-9-THC, like other CB(1)R agonists and
      endocannabinoid enhancers, may possess antidepressant properties at low doses,
      and could modulate 5-HT transmission in the DR and hippocampus as standard
      antidepressants such as selective serotonin reuptake inhibitors.

PMID- 22386779
TI  - Ex vivo expansion of limbal stem cells is affected by substrate properties.
AB  - Limbal epithelial stem cells play a key role in the maintenance and regulation of
      the corneal surface. Damage or destruction of these cells results in
      vascularisation and corneal opacity. Subsequent limbal stem cell transplantation
      requires an ex vivo expansion step and preserving cells in an undifferentiated
      state remains vital. In this report we seek to control the phenotype of limbal
      epithelial stem cells by the novel application of compressed collagen substrates.
      We have characterised the mechanical and surface properties of conventional
      collagen gels using shear rheology and scanning electron microscopy. In doing so,
      we provide evidence to show that compressive load can improve the stiffness of
      collagen substrates. In addition Western blotting and immunohistochemistry
      display increased cytokeratin 3 (CK3) protein expression relating to limbal
      epithelial cell differentiation on stiff collagen substrates. Such gels with an
      elastic modulus of 2900 Pa supported a significantly higher number of cells than
      less stiff collagen gels (3 Pa). These findings have substantial influence in the
      development of ocular surface constructs or experimental models particularly in
      the fields of stem cell research, tissue engineering and regenerative medicine.

PMID- 22386780
TI  - On the neural substrates for exploratory dynamics in basal ganglia: a model.
AB  - We present a neural network model of basal ganglia that departs from the
      classical Go/NoGo picture of the function of its key pathways-the direct pathway
      (DP) and the indirect pathway (IP). In classical descriptions of basal ganglia
      function, the DP is known as the Go pathway since it facilitates movement and the
      IP is called the NoGo pathway since it inhibits movement. Between these two
      regimes, in the present model, we posit that there is a third Explore regime,
      which denotes random exploration of the space of actions. The proposed model is
      instantiated in a simple action selection task. Striatal dopamine is assumed to
      switch between DP and IP activation. The IP is modeled as a loop of the
      subthalamic nucleus (STN) and the globus pallidus externa (GPe), capable of
      producing chaotic activity. Simulations reveal that, while the system displays Go
      and NoGo regimes for extreme values of dopamine, at intermediate values of
      dopamine, it exhibits a new Explore regime denoting a random exploration of the
      space of action alternatives. The exploratory dynamics originates from the
      chaotic activity of the STN-GPe loop. When applied to the standard card choice
      experiment used in the imaging studies of Daw, O'Doherty, Dayan, Seymour, and
      Dolan (2006), the model favorably describes the exploratory behavior of human
      subjects.

PMID- 22386781
TI  - Neural networks and the experience and cultivation of mind.
AB  - Hard core neural network research includes development of mathematical models of
      cognitive prediction and optimization aimed at dual use, both as models of what
      we see in brain circuits and behavior, and as useful general-purpose engineering
      technology. The pathway and principles now exist to let us someday replicate
      learning abilities as elevated as what we see in the brain of the mouse-but how
      can this help us today in understanding and maximizing the much greater potential
      of the human mind, as addressed by many schools of thought all over the world for
      centuries? This paper discusses how we might use what we have learned at a lower
      level to better illuminate key phenomena in first person and clinical human
      experience such as Freud's "psychic energy", the role of traumatic experience,
      the interpretation of dreams, creativity, the cultivation of sanity and
      sensitivity, and the biological foundations of language.

PMID- 22386782
TI  - An extended echo state network using Volterra filtering and principal component
      analysis.
AB  - Echo state networks (ESNs) can be interpreted as promoting an encouraging
      compromise between two seemingly conflicting objectives: (i) simplicity of the
      resulting mathematical model and (ii) capability to express a wide range of
      nonlinear dynamics. By imposing fixed weights to the recurrent connections, the
      echo state approach avoids the well-known difficulties faced by recurrent neural
      network training strategies, but still preserves, to a certain extent, the
      potential of the underlying structure due to the existence of feedback loops
      within the dynamical reservoir. Moreover, the overall training process is
      relatively simple, as it amounts essentially to adapting the readout, which
      usually corresponds to a linear combiner. However, the linear nature of the
      output layer may limit the capability of exploring the available information,
      since higher-order statistics of the signals are not taken into account. In this
      work, we present a novel architecture for an ESN in which the linear combiner is
      replaced by a Volterra filter structure. Additionally, the principal component
      analysis technique is used to reduce the number of effective signals transmitted
      to the output layer. This idea not only improves the processing capability of the
      network, but also preserves the simplicity of the training process. The proposed
      architecture is then analyzed in the context of a set of representative
      information extraction problems, more specifically supervised and unsupervised
      channel equalization, and blind separation of convolutive mixtures. The obtained
      results, when compared to those produced by already proposed ESN versions,
      highlight the benefits brought by the novel network proposal and characterize it
      as a promising tool to deal with challenging signal processing tasks.

PMID- 22386783
TI  - Multi-column deep neural network for traffic sign classification.
AB  - We describe the approach that won the final phase of the German traffic sign
      recognition benchmark. Our method is the only one that achieved a better-than
      human recognition rate of 99.46%. We use a fast, fully parameterizable GPU
      implementation of a Deep Neural Network (DNN) that does not require careful
      design of pre-wired feature extractors, which are rather learned in a supervised
      way. Combining various DNNs trained on differently preprocessed data into a Multi
      Column DNN (MCDNN) further boosts recognition performance, making the system
      insensitive also to variations in contrast and illumination.

PMID- 22386784
TI  - Fault-tolerant nonlinear adaptive flight control using sliding mode online
      learning.
AB  - An expanded nonlinear model inversion flight control strategy using sliding mode
      online learning for neural networks is presented. The proposed control strategy
      is implemented for a small unmanned aircraft system (UAS). This class of aircraft
      is very susceptible towards nonlinearities like atmospheric turbulence, model
      uncertainties and of course system failures. Therefore, these systems mark a
      sensible testbed to evaluate fault-tolerant, adaptive flight control strategies.
      Within this work the concept of feedback linearization is combined with feed
      forward neural networks to compensate for inversion errors and other nonlinear
      effects. Backpropagation-based adaption laws of the network weights are used for
      online training. Within these adaption laws the standard gradient descent
      backpropagation algorithm is augmented with the concept of sliding mode control
      (SMC). Implemented as a learning algorithm, this nonlinear control strategy
      treats the neural network as a controlled system and allows a stable, dynamic
      calculation of the learning rates. While considering the system's stability, this
      robust online learning method therefore offers a higher speed of convergence,
      especially in the presence of external disturbances. The SMC-based flight
      controller is tested and compared with the standard gradient descent
      backpropagation algorithm in the presence of system failures.

PMID- 22386785
TI  - Metamodeling and the Critic-based approach to multi-level optimization.
AB  - Large-scale networks with hundreds of thousands of variables and constraints are
      becoming more and more common in logistics, communications, and distribution
      domains. Traditionally, the utility functions defined on such networks are
      optimized using some variation of Linear Programming, such as Mixed Integer
      Programming (MIP). Despite enormous progress both in hardware (multiprocessor
      systems and specialized processors) and software (Gurobi) we are reaching the
      limits of what these tools can handle in real time. Modern logistic problems, for
      example, call for expanding the problem both vertically (from one day up to
      several days) and horizontally (combining separate solution stages into an
      integrated model). The complexity of such integrated models calls for alternative
      methods of solution, such as Approximate Dynamic Programming (ADP), which provide
      a further increase in the performance necessary for the daily operation. In this
      paper, we present the theoretical basis and related experiments for solving the
      multistage decision problems based on the results obtained for shorter periods,
      as building blocks for the models and the solution, via Critic-Model-Action
      cycles, where various types of neural networks are combined with traditional MIP
      models in a unified optimization system. In this system architecture, fast and
      simple feed-forward networks are trained to reasonably initialize more
      complicated recurrent networks, which serve as approximators of the value
      function (Critic). The combination of interrelated neural networks and
      optimization modules allows for multiple queries for the same system, providing
      flexibility and optimizing performance for large-scale real-life problems. A
      MATLAB implementation of our solution procedure for a realistic set of data and
      constraints shows promising results, compared to the iterative MIP approach.

PMID- 22386786
TI  - Orthogonal least squares based complex-valued functional link network.
AB  - Functional link networks are single-layered neural networks that impose
      nonlinearity in the input layer using nonlinear functions of the original input
      variables. In this paper, we present a fully complex-valued functional link
      network (CFLN) with multivariate polynomials as the nonlinear functions. Unlike
      multilayer neural networks, the CFLN is free from local minima problem, and it
      offers very fast learning of parameters because of its linear structure.
      Polynomial based CFLN does not require an activation function which is a major
      concern in the complex-valued neural networks. However, it is important to select
      a smaller subset of polynomial terms (monomials) for faster and better
      performance since the number of all possible monomials may be quite large. Here,
      we use the orthogonal least squares (OLS) method in a constructive fashion
      (starting from lower degree to higher) for the selection of a parsimonious subset
      of monomials. It is argued here that computing CFLN in purely complex domain is
      advantageous than in double-dimensional real domain, in terms of number of
      connection parameters, faster design, and possibly generalization performance.
      Simulation results on a function approximation, wind prediction with real-world
      data, and a nonlinear channel equalization problem exhibit that the OLS based
      CFLN yields very simple structure having favorable performance.

PMID- 22386787
TI  - Hierarchical curiosity loops and active sensing.
AB  - A curious agent acts so as to optimize its learning about itself and its
      environment, without external supervision. We present a model of hierarchical
      curiosity loops for such an autonomous active learning agent, whereby each loop
      selects the optimal action that maximizes the agent's learning of sensory-motor
      correlations. The model is based on rewarding the learner's prediction errors in
      an actor-critic reinforcement learning (RL) paradigm. Hierarchy is achieved by
      utilizing previously learned motor-sensory mapping, which enables the learning of
      other mappings, thus increasing the extent and diversity of knowledge and skills.
      We demonstrate the relevance of this architecture to active sensing using the
      well-studied vibrissae (whiskers) system, where rodents acquire sensory
      information by virtue of repeated whisker movements. We show that hierarchical
      curiosity loops starting from optimally learning the internal models of whisker
      motion and then extending to object localization result in free-air whisking and
      object palpation, respectively.

PMID- 22386788
TI  - Nonlinear dynamics and chaos in fractional-order neural networks.
AB  - Several topics related to the dynamics of fractional-order neural networks of
      Hopfield type are investigated, such as stability and multi-stability
      (coexistence of several different stable states), bifurcations and chaos. The
      stability domain of a steady state is completely characterized with respect to
      some characteristic parameters of the system, in the case of a neural network
      with ring or hub structure. These simplified connectivity structures play an
      important role in characterizing the network's dynamical behavior, allowing us to
      gain insight into the mechanisms underlying the behavior of recurrent networks.
      Based on the stability analysis, we are able to identify the critical values of
      the fractional order for which Hopf bifurcations may occur. Simulation results
      are presented to illustrate the theoretical findings and to show potential routes
      towards the onset of chaotic behavior when the fractional order of the system
      increases.

PMID- 22386789
TI  - Using GNG to improve 3D feature extraction--application to 6DoF egomotion.
AB  - Several recent works deal with 3D data in mobile robotic problems, e.g. mapping
      or egomotion. Data comes from any kind of sensor such as stereo vision systems,
      time of flight cameras or 3D lasers, providing a huge amount of unorganized 3D
      data. In this paper, we describe an efficient method to build complete 3D models
      from a Growing Neural Gas (GNG). The GNG is applied to the 3D raw data and it
      reduces both the subjacent error and the number of points, keeping the topology
      of the 3D data. The GNG output is then used in a 3D feature extraction method. We
      have performed a deep study in which we quantitatively show that the use of GNG
      improves the 3D feature extraction method. We also show that our method can be
      applied to any kind of 3D data. The 3D features obtained are used as input in an
      Iterative Closest Point (ICP)-like method to compute the 6DoF movement performed
      by a mobile robot. A comparison with standard ICP is performed, showing that the
      use of GNG improves the results. Final results of 3D mapping from the egomotion
      calculated are also shown.

PMID- 22386790
TI  - Role of MINOS in mitochondrial membrane architecture and biogenesis.
AB  - Mitochondria possess a complex architecture with two membranes. The inner
      membrane is divided into two domains: the inner boundary membrane, which is
      adjacent to the outer membrane, and membrane invaginations termed cristae. Both
      domains are connected by tubular openings, the crista junctions. Recent studies
      led to the identification of a large protein complex that is crucial for
      establishing inner-membrane architecture. This mitochondrial inner-membrane
      organizing system (MINOS) interacts with protein translocases of the outer
      membrane that are functionally connected to the endoplasmic reticulum (ER)
      mitochondria encounter structure. Here, we propose that MINOS forms a central
      part of an ER-mitochondria organizing network (ERMIONE) that controls
      mitochondrial membrane architecture and biogenesis.

PMID- 22386791
TI  - Uranium removal from water using cellulose triacetate membranes added with
      activated carbon.
AB  - Ultrafiltration removal of uranium from water, with composite activated carbon
      cellulose triacetate membranes (AC-CTA), was investigated. The filtrate was
      provided by uraninite dissolution with pH=6-8. Removal efficiencies were
      calculated measuring solutions' radioactivities. Membranes were mainly
      characterized by microscopy analysis, revealing iron after permeation. Uranyl
      removal was 35+/-7%. Chemical speciation indicates the presence of
      (UO(2))(2)CO(3)(OH)(3)(-), UO(2)CO(3), UO(2)(CO(3))(2)(2-) and Fe(2)O(3)(s) as
      main compounds in the dissolution, suggesting co-adsorption of uranium and iron
      by the AC during filtration, as the leading rejection path.

PMID- 22386792
TI  - Human leukocyte antigen-DQ beta 1 chain (DQB1) gene polymorphisms are associated
      with dilated cardiomyopathy: a systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies reported an association between the human leukocyte
      antigen (HLA)-DQ antigen beta 1 chain (DQB1) alleles and dilated cardiomyopathy
      (DCM). However, the results of those studies have been inconsistent. To clarify
      the association between HLA-DQB1 and DCM, we performed a systematic review and
      meta-analysis of case-control studies. METHODS: Searches were performed using the
      PubMed database, the Excerpta Medica Database (EMBASE), the Cochrane Central
      Register of Controlled Trials database, the Science Citation Index database, the
      China Biology Medicine disc, the China National Knowledge Information database,
      the Wanfang database, and the Chinese Scientific and Technological Journal
      Database (VIP database). The search terms included "dilated cardiomyopathy" and
      "DQB1." Ten case-controlled studies were included in the systematic review to
      assess the association between DCM and the HLA-DQB1*0201, *0302, *0504, *0301,
      and *0602 alleles. RESULTS: In total, 8 studies were included in the meta
      analysis of the HLA-DQB1 *0201 allele. The pooled odds risk (OR) for this allele
      was .47, with a 95% confidence interval (CI) of .28 to .77 (P < .01). With
      respect to the HLA-DQB1 *0504 allele, only 3 studies were included in our meta
      analysis. The pooled OR was .36 (95% CI, .15 to .84; P < .05). Nine, 8, and 7
      studies of the HLA-DQB1 *0301, *0302, and *0602 alleles, respectively, were
      included in our meta-analysis. No statistically significant difference was
      evident in the frequency of these 3 alleles between the DCM and normal control
      groups. CONCLUSION: The HLA-DQB1 *0201 and *0504 alleles may be protective
      against DCM.

PMID- 22386793
TI  - Adsorption of Cu(II), Cd(II) and Ni(II) ions by cross-linked magnetic chitosan-2
      aminopyridine glyoxal Schiff's base.
AB  - The adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solution by cross
      linked magnetic chitosan-2-aminopyridine glyoxal Schiff's base resin (CSAP) was
      studied in a batch adsorption system. Cu(II), Cd(II) and Ni(II) removal is pH
      dependent and the optimum adsorption was observed at pH 5.0. The adsorption was
      fast with estimated initial rate of 2.7, 2.4 and 1.4 mg/(g min) for Cu(2+),
      Cd(2+) and Ni(2+) respectively. The adsorption data could be well interpreted by
      the Langmuir, Freundlich and Temkin model. The maximum adsorption capacities
      obtained from the Langmuir model were 124+/-1, 84+/-2 and 67+/-2 mg g(-1) for
      Cu(2+), Cd(2+) and Ni(2+) respectively. The adsorption process could be described
      by pseudo-second-order kinetic model. Thermodynamic parameters revealed the
      feasibility, spontaneity and exothermic nature of adsorption. The sorbents were
      successfully regenerated using EDTA and HCl solutions.

PMID- 22386794
TI  - Adsorption behaviors of recombinant E-cadherin-IgG Fc fusion protein on
      polystyrene surface.
AB  - Adsorption behaviors of recombinant E-cadherin-IgG Fc (E-cad-Fc) fusion protein
      and mutated E-cad-Fcs on the polystyrene (PS) surface were investigated using a
      27 MHz quartz-crystal microbalance (QCM) and ELISA. The amount of adsorbed E-cad
      Fc on PS surface was increased with an increase of E-cad-Fc concentration as a
      Langmuir-type in a monolayer. Adsorbed E-cad-Fc on PS surface was stable even
      after washing if calcium ions are absent in the washing solution due to the
      calcium ion dependence in the adsorption. E-cadherin homophilic adhesion among E
      cadherins during adsorption of E-cad-Fc was involved. Deglycosylation of the E
      cad in the E-cad-Fc did not affect adsorption of E-cad-Fc on the PS surface
      although deglycosylation of the E-cad in the E-cad-Fc enhanced cell adhesion
      compared with E-cad-Fc.

PMID- 22386795
TI  - Entrapment and release kinetics of furosemide from pegylated nanocarriers.
AB  - This study was designed to test the hypothesis that furosemide (Fur) can be
      entrapped into surfactant free pegylated nanocarriers (NCs) for controlled drug
      release. To test this hypothesis, Fur-loaded NCs were prepared by emulsion
      solvent diffusion method. A 2(3) factorial design was used to optimize the effect
      of three formulation variables [amounts of Fur (X(1)), poly(lactic-co-glycolic
      acid) (X(2)) and poly-epsilon-caprolactone-polyethylene glycol (X(3))] on
      particle mean diameter (Y(1)), polydispersity index (PDI, Y(2)), and percent drug
      encapsulation efficiency (EE%, Y(3)). The NCs were characterized for morphology,
      thermal behavior, optical properties, crystallinity, and drug release kinetics
      using electron microscopy (EM), differential scanning calorimetry (DSC), Fourier
      transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and high
      performance liquid chromatography, respectively. The optimum formula produced
      with 6 mg of Fur, 7 mg of PLGA, and 1mg of PCL-PEG corresponded to 183.26 nm,
      0.26, and 88.29% as Y(1), Y(2) and Y(3) values, respectively. DSC thermograms,
      FTIR spectra and PXRD diffractograms indicated that Fur was encapsulated in its
      polymorphic crystalline form I within the NCs polymeric matrix. This was further
      confirmed by a comparative study between native Fur, Fur nanocrystal and Fur
      loaded NCs using scanning EM, PXRD and drug release kinetics. The release
      kinetics of the optimized formula fit the Higuchi model indicating that the drug
      was released by diffusion in 12h. These results indicate that pegylated Fur
      loaded NCs could be successfully prepared with high EE% and sustained release
      profile intended for the inner ear drug delivery.

PMID- 22386797
TI  - [An interesting experience on the use of information and population data bases].
AB  - INTRODUCTION: In order to support decisions and analyze outcomes, the Spanish
      Health System has shown a great interest in developing data bases and high
      quality information systems. Nevertheless the use of these data bases are
      limited, not very systematized and, some times, their accessibility may be
      difficult. MATERIAL AND METHODS: We describe in this review the experience in
      using the Institute for Clinical Evaluative Science (ICES, Ontario, Canada) as an
      efficient model to improve the usefulness of these data bases. RESULTS: Under
      restrictive conditions of confidentiality and privacy, the ICES has the legal
      capacity to use several population based data bases, for research projects and
      reports. ICES's functional structure (with an administrative and scientific
      level) is an interesting framework since it guarantees its independent and
      economic assessment. DISCUSSION: To date, its scientific production has been high
      in many areas of knowledge and open to those interested, with points of view of
      many health care professionals (including management), for whom the quality of
      research is of the ultimate importance, to be able to access these resources.

PMID- 22386796
TI  - Understanding the complexity of IgE-related phenotypes from childhood to young
      adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.
AB  - Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program
      European Union project, aims to generate novel knowledge on the mechanisms of
      initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will
      be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January
      24, 2011, to review current knowledge on the IgE-related phenotypes and to
      explore how a multidisciplinary effort could result in a new integrative
      translational approach. This article provides a summary of the meeting. It
      develops challenges in IgE-related phenotypes and new clinical and epidemiologic
      approaches to the investigation of allergic phenotypes, including cluster
      analysis, scale-free models, candidate biomarkers, and IgE microarrays; the
      particular case of severe asthma was reviewed. Then novel approaches to the IgE
      associated phenotypes are reviewed from the individual mechanisms to the systems,
      including epigenetics, human in vitro immunology, systems biology, and animal
      models. The last chapter deals with the understanding of the population-based IgE
      associated phenotypes in children and adolescents, including age effect in terms
      of maturation, observed effects of early-life exposures and shift of focus from
      early life to pregnancy, gene-environment interactions, cohort effects, and time
      trends in patients with allergic diseases. This review helps to define phenotypes
      of allergic diseases in MeDALL.

PMID- 22386798
TI  - Is there a requirement for axillary lymph node dissection following
      identification of micro-metastasis or isolated tumour cells at sentinel node
      biopsy for breast cancer?
AB  - INTRODUCTION: Recent decades have seen a significant shift towards conservative
      management of the axilla. Increasingly, immunohistochemical analysis of sentinel
      nodes leads to the detection of small tumour deposits, the significance of which
      remains uncertain. The aims of this study are to examine patients whose sentinel
      lymph nodes are positive for macro-metastasis, micro-metastasis or isolated
      tumour cells (ITCs) and to determine the rate of further nodal disease after
      axillary lymph node dissection (ALND). METHODS: A retrospective analysis of all
      patients undergoing a sentinel lymph node biopsy (SLNB) between January 2007 and
      December 2010 in a tertiary referral breast unit was performed. Patients who
      underwent an axillary lymph node dissection for macro-metastasis, micro
      metastasis or ITCs were identified. Demographics, histological data and the rate
      of further axillary disease were examined. RESULTS: In total, 664 breast cancer
      patients attended the symptomatic breast unit during the study period, 360 of
      whom underwent a SLNB. Seventy patients had a SLNB positive for macro-metastasis.
      All of these patients underwent ALND. A positive SLNB with either micro
      metastasis or ITCs was identified in 58 patients. Only 41 of the 58 patients went
      on to have an ALND, due primarily to variations in surgeons' preferences.
      Nineteen patients with micro-metastasis underwent an ALND. Four patients had
      further axillary disease (21%). Twenty-two patients had ITCs identified, of whom
      only one had further disease (4.5%). No statistically significant difference was
      found between the two groups in terms of tumour size, grade, lymphovascular
      invasion or oestrogen receptor status. CONCLUSION: ALND should be considered in
      patients with micro-metastasis at SLNB. It should rarely be employed in the
      setting of SLNB positive for ITCs.

PMID- 22386799
TI  - Design and rationale of a randomized controlled trial to reduce cardiovascular
      disease risk for patients with bipolar disorder.
AB  - BACKGROUND: Persons with bipolar disorder (BD) experience a disproportionate
      burden of medical comorbidity, notably cardiovascular disease (CVD), contributing
      to decreased function and premature mortality. We describe the design, rationale,
      and baseline findings for the Self-Management Addressing Heart Risk Trial
      (SMAHRT), a randomized controlled effectiveness trial of an intervention (Life
      Goals Collaborative Care; LGCC) designed to reduce CVD risk factors and improve
      physical and mental health outcomes in patients with BD. METHODS: Patients with
      BD and at least one CVD risk factor were recruited from a VA healthcare system
      and randomized to either LGCC or usual care (UC). LGCC participants attended four
      weekly, group-based self-management sessions followed by monthly individual
      contacts supportive of health behavior change and ongoing medical care
      management. In contrast, UC participants received monthly wellness newsletters.
      Physiological and questionnaire assessments measured changes in CVD outcomes and
      quality of life (QOL) over 24 months. RESULTS: Out of the 180 eligible patients,
      134 patients were enrolled (74%) and 118 started the study protocols. At baseline
      (mean age=54, 17% female, 5% African American) participants had a high burden of
      clinical risk with nearly 70% reporting at least three CVD risk factors
      including, smoking (41%) and physical inactivity (57%). Mean mental and physical
      HRQOL scores were 1.5 SD below SF-12 population averages. CONCLUSION: SMAHRT
      participants experienced substantial CVD morbidity and risk factors, poor symptom
      control, and decreased QOL. LGCC is the first integrated intervention for BD
      designed to mitigate suboptimal health outcomes by combining behavioral medicine
      and care management strategies.

PMID- 22386800
TI  - Heavy metals contamination levels at the Coast of Aliaga (Turkey) ship recycling
      zone.
AB  - Aliaga Bay is one of the most important maritime zones of Turkey where shipping
      activity, shipbreaking industry, steel works and petrochemical complexes exist
      together. Concentrations of heavy metals and organic carbon in sediment of the
      Aliaga Bay were investigated to evaluate an environmental risk assessment from
      metals contamination in 2009-2010. Comparison of the metal concentrations with
      average shale and Mediterranean background levels revealed that most of the
      samples from the Aliaga were polluted with Hg, Cd, Pb, Cr, Cu, Zn, Mn and Ni. It
      was found that Hg, Pb, Cu, Zn and Ni levels in Aliaga Bay exceeded the PEL
      values. Sediments, contaminated with Pb, Cr, Cu, Zn and Ni were considered as
      heavily polluted per the SQG.

PMID- 22386801
TI  - Benthic recovery after fish farming cessation: a "beyond-BACI" approach.
AB  - The development of a benthic environment after fish-farming cessation was
      examined. To ascertain whether recovery occurred, several abiotic (granulometry,
      acid-volatile sulfides, total phosphorus and redox potential) and biotic
      (polychaete abundance) variables were monitored using a "beyond-BACI" approach.
      Before the cessation of farming, the geochemical conditions and polychaete
      assemblages differed among the impacted and control sites. After cessation, an
      improvement of the geochemical conditions was achieved. A significant tendency
      toward a recovery of the polychaete assemblage in the impacted area was observed,
      but significant differences still remained compared with the control sites. The
      acid-volatile sulfide level was responsible for these differences. The abundance
      of polychaete families associated with organically enriched sediments diminished
      at the impacted site after cessation, whereas the abundance of some sensitive and
      omnivorous families increased. The "beyond-BACI" approach provided a wider
      framework than other approaches, enabling us to differentiate the natural
      variability from those changes induced by the fish farm and farming cessation.

PMID- 22386802
TI  - Anthropogenic "Litter" and macrophyte detritus in the deep Northern Gulf of
      Mexico.
AB  - A deep-sea trawl survey of the Northern Gulf of Mexico has documented the
      abundance and diversity of human-generated litter and natural detrital plant
      material, from the outer margin of the continental shelf out to the Sigsbee
      abyssal plain. Plastics were the most frequently encountered type of material.
      Litter and debris were encountered more frequently in the eastern than in the
      western GoM. Land-derived plant material was located primarily within the head of
      the Mississippi Canyon, whereas ocean-derived plant material was spread evenly
      throughout the NE GoM. Human discards were principally from ships offshore. Some
      of the material was contained in metal cans that sank to the sea floor, probably
      in order to conform to international agreements that prohibit disposal of toxic
      material and plastics. The Mississippi Canyon was a focal point for litter,
      perhaps due to topography, currents or proximity to shipping lanes.

PMID- 22386803
TI  - Structure and hydrogel formation studies on homologs of a lactoglobulin-derived
      peptide.
AB  - In order to study the impact of the amino acid sequence on the morphology of
      peptide-based nanostructures and their hydrogel formation, we designed a series
      of analogs of a milk-derived octapeptide (OP), mainly using strategic amino acid
      substitutions. Electronic transmission microscopy (TEM) and circular dichroism
      (CD) spectropolarimetry were used to analyze the nanostructures formed, and to
      characterize some structural features of the modified peptides. Further, the
      potential to form hydrogels was investigated for all of the analogous peptides.
      We learned that those able to undergo secondary structure transition to beta
      sheet conformation form strong gels. The results reported highlight some key
      structural properties that explain the self-assembly propensity of Peptide OP.

PMID- 22386804
TI  - Clinical assessments of increased sensory sensitivity in dogs with cranial
      cruciate ligament rupture.
AB  - Dogs with chronic pain have a compromised quality of life. Repeatable and
      accurate sensory assessments form a means by which the hypersensitivity likely to
      reflect chronic pain may be quantified. These assessments can be applied to
      individuals to identify those that may benefit from improved analgesic relief. In
      this study four sensory assessments were evaluated in dogs presenting with a
      naturally occurring chronic painful condition (cranial cruciate ligament rupture,
      CCLR) and were compared with healthy control animals of similar age and weight.
      Inter-digital von Frey filament and thermal sensitivity tests revealed that the
      affected hind limb of dogs with CCLR was significantly more sensitive than the
      opposing limb. Static weight bearing and gait parameter scores were also reduced
      in the affected hind limb compared to the opposing hind limb of dogs with CCLR;
      no such differences were found between the hind limbs of healthy (control) dogs.
      The quantitative sensory tests permitted the differentiation of limbs affected by
      CCLR from healthy limbs. Dogs presenting with CCLR demonstrate objectively
      quantitative sensory sensitivities, which may require additional consideration in
      case management.

PMID- 22386805
TI  - In vitro development and characterization of canine epidermis on a porcine
      acellular dermal matrix.
AB  - The aim of this study was to develop and to characterize a canine skin epidermal
      model able to form a proper epidermis on a porcine acellular dermal matrix
      (PADM). In addition, the role of fibroblasts in skin barrier formation was
      studied by incorporating or omitting canine dermal fibroblasts in the PADM.
      Canine epidermal composites were developed by seeding keratinocytes onto the
      surface of PADM that were previously seeded or non-seeded with dermal
      fibroblasts. After 14 days of culture under air-exposed conditions and in a
      special growth medium, skin composites were histologically processed and
      immunohistochemically characterized to determine the expression of cytokeratins
      and of vimentin and the presence of basement membrane. In all composites,
      keratinocytes underwent differentiation to a multilayer epidermis with 5-7 viable
      cell layers. The stratum basalis, stratum spinosum, stratum granulosum and
      stratum corneum were identified. The expression of cytokeratins was similar to
      that described in healthy canine epidermis. Laminin and collagen IV
      immunostaining revealed a homogeneous layer in the epidermal-dermal junction only
      when the matrix had been seeded by canine dermal fibroblasts. The model may
      become a simple, useful and cost-effective tool to investigate the biology and
      pathology of canine epidermis and could partially replace animal testing in
      several areas of dermatological research.

PMID- 22386806
TI  - Long-term survivors among patients with cancer of unknown primary.
AB  - There is a general conception among oncologists that CUP patients behave poorly
      to treatment and carry a dismal survival. In this paper we are trying to
      elucidate the different groups of CUP patients and to describe in details the
      diagnostic and therapeutic management of the prognostically favorable patients.
      Clinicians should be aware that the favorable CUP cases must be treated according
      to recent guidelines with either specific locoregional and/or systemic therapy
      and that they commonly enjoy a long survival. Survival data of 219 CUP patients
      treated at Ioannina University Hospital from 1995 until 2011 are also presented.

PMID- 22386807
TI  - Cancer education for medical students in developing countries: where do we stand
      and how to improve?
AB  - BACKGROUND: This article is a review of the literature regarding the state of
      oncology education for medical students in developing countries, and possible
      solutions to the problems at hand. METHODS: Ovid MEDLINE, PubMed, ERIC, The
      Cochrane CENTRAL Register of Controlled Trials (CENTRAL) and Google Scholar were
      searched using the terms oncology, undergraduate, cancer, education and teaching.
      RESULTS: The search resulted in 40 relevant articles in total. Ten articles
      showed that there is a lack of adequate knowledge in the scientific, clinical and
      psychological aspects of oncology and palliative care amongst students and
      physicians in developing countries. Eight articles describe the relevance and
      usefulness of summer schools, workshops and trainings. The rest of them discuss
      possible methods of addressing the issue, the most important of which is the
      inclusion of a clinical oncology rotation in the undergraduate syllabus.
      CONCLUSION: Graduated physicians and medical students are a long way from
      reaching the standard knowledge and skills required in oncology. Thus, there is a
      pressing need to reform the undergraduate medical curricula in developing
      countries in order to increase cancer awareness for better graduated future
      physicians.

PMID- 22386808
TI  - Assessment of reduced glutathione: comparison of an optimized fluorometric assay
      with enzymatic recycling method.
AB  - Glutathione is an important tripeptide involved in a variety of cellular
      processes. Thus, precise knowledge of its levels is essential. Glutathione exists
      in two free forms-reduced and oxidized-and a number of methods exist to measure
      its levels. The aim of our work was to optimize a spectrofluorometric assay for
      reduced glutathione based on the reaction between glutathione and o
      phthalaldehyde. We found that a change of excitation wavelength to 340 nm and
      modification of pH to 6.0 enhance sensitivity and specificity of the method
      (intraassay coefficient of variation CV < 3%, interassay CV = 5.1%, recovery = 98
      102%, linearity = 0-1000 MUM GSH, calibration R2 = 1.00). We also anticipated
      possible effect of various amino acids on the fluorescence signal, but no
      interference was found. We compared the optimized fluorometric method with a
      popular enzymatic recycling glutathione assay and found very strong correlation
      of results (r = 0.99, n = 45). We introduce here an optimized fluorometric method
      possessing sufficient sensitivity and specificity that is comparable to the
      enzymatic glutathione assay. Because the fluorometric assay procedure is faster
      and lower in cost, it could be ideal for routine analysis of reduced glutathione
      levels in a large number of samples.

PMID- 22386809
TI  - Subchronic toxicity and mutagenicity/genotoxicity studies of Irvingia gabonensis
      extract (IGOB131).
AB  - African Bush Mango from Irvingia gabonensis is a West African culinary fruit and
      the mucilage from this fruit seed is used to make traditional soups and sauces.
      Extract from the kernel (IGOB131) has been claimed for its health benefits. In
      the present investigations, potential adverse effects, if any, of IGOB131 were
      investigated in dose-response 90-day study and genotoxicity studies. In the
      subchronic study, Sprague Dawley rats (20/sex/group) were gavaged with I.
      gabonensis extract (IGOB131) at dose levels of 0, 100, 1000 and 2500 mg/kg body
      weight (bw)/day for 90-days. No treatment-related changes in clinical signs,
      functional observations, mortality, ophthalmologic observations, body weights,
      body weight gain or feed consumption were noted. Similarly, hematological,
      clinical chemistry, urine analysis parameters, and organ weights did not reveal
      any toxicologically significant treatment-related changes. No treatment-related
      macroscopic and microscopic abnormalities were noted at the end of treatment
      period. The mutagenicity as evaluated by Ames assay, in vitro and in vivo
      chromosomal aberration test and in vivo micronucleus assay did not reveal any
      genotoxicity of IGOB131. The results of subchronic toxicity study suggest the no
      observed-adverse-effect level (NOAEL) for I. gabonensis extract (IGOB131) as >=
      2500 mg/kg bw/day, the highest dose tested.

PMID- 22386810
TI  - Identification of novel mechanisms of silymarin on the carbon tetrachloride
      induced liver fibrosis in mice by nuclear factor-kappaB bioluminescent imaging
      guided transcriptomic analysis.
AB  - In this study, we applied bioluminescent imaging-guided transcriptomic analysis
      to evaluate and identify the therapeutic potentials and novel mechanisms of
      silymarin on carbon tetrachloride (CCl(4))-induced liver fibrosis. Transgenic
      mice, carrying the luciferase genes driven by nuclear factor-kappaB (NF-kappaB),
      were given with CCl(4) and/or silymarin. In vivo NF-kappaB activity was evaluated
      by bioluminescent imaging, liver fibrosis was judged by Sirius red staining and
      immunohistochemistry, and gene expression profiles of silymarin-treated livers
      were analyzed by DNA microarray. CCl(4) enhanced the NF-kappaB-dependent hepatic
      luminescence and induced hepatic fibrosis, while silymarin reduced the CCl(4)
      induced hepatic luminescence and improved CCl(4)-induced liver fibrosis.
      Microarray analysis showed that silymarin altered the transforming growth factor
      beta-mediated pathways, which play pivotal roles in the progression of liver
      fibrosis. Moreover, we newly identified that silymarin downregulated the
      expression levels of cytoskeleton organization genes and mitochondrion electron
      transfer chain genes, such as cytochrome c oxidase Cox6a2, Cox7a1, and Cox8b
      genes. In conclusion, the correlation of NF-kappaB-dependent luminescence and
      liver fibrosis suggested the feasibility of NF-kappaB bioluminescent imaging for
      the evaluation of liver fibrosis progression and therapeutic potentials.
      Moreover, our findings suggested that silymarin might exhibit anti-fibrotic
      effects in vivo via altering the expression of genes involved in cytoskeleton
      organization and mitochondrion electron-transfer chain.

PMID- 22386811
TI  - Comparative study of beta-carotene and microencapsulated beta-carotene:
      evaluation of their genotoxic and antigenotoxic effects.
AB  - beta-Carotene (BC) is one of the natural pigments that is most commonly added to
      food; however, the utilization of BC is limited due to its instability.
      Microencapsulation techniques are commonly used because they can protect the
      microencapsulated material from oxidization. Nevertheless, the properties of the
      encapsulated compounds must be studied. We compared the antigenotoxic potential
      of pure and microencapsulated beta-carotene (mBC) in Wistar rats. Two doses of BC
      or mBC (2.5 or 5.0 mg/kg) were administered by gavage over a period of 14 days.
      The final gavage was followed by an injection of doxorubicin (DXR). After 24h the
      animals were euthanized. The micronucleus test results showed that when both mBC
      and DXR were given, only the higher dose was antigenotoxic. The results of the
      comet assay show that when given in association with DXR, mBC had protective
      effects in the liver. The differences between the results obtained with BC and
      mBC suggest that possibly the carotenoid biodisponibility was modified by the
      process of microencapsulation. In conclusion, mBC does not lose its protective
      properties, but higher doses must be used to observe antigenotoxic effects. This
      is the first time that the genotoxicity and antigenotoxicity of a
      microencapsulated compound was evaluated in vivo.

PMID- 22386812
TI  - Purification and characterization of a nitric oxide inhibitory peptide from
      Ruditapes philippinarum.
AB  - Ruditapes philippinarum (R. philippinarum) were hydrolyzed using 8 proteases to
      produce an anti-inflammatory peptide of the various hydrolysates produced, the
      Alcalase hydrolysate exhibited the highest nitric oxide (NO) inhibitory activity.
      The derived peptide was purified using high performance liquid chromatography
      (HPLC) and NO-inhibitory activity of the purified compound was evaluated. The
      sequence of the NO-inhibitory peptide obtained was composed of 10 amino acid
      residues, Gln-Cys-Gln-Gln-Ala-Val-Gln-Ser-Ala-Val at N-terminal position. In
      addition, we investigated the inhibitory effect of the purified peptide from R.
      philippinarum on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7
      cells. In this analysis the purified peptide from R. philippinarum was shown to
      inhibit LPS-induced NO production in RAW264.7 cells. The present results indicate
      that the purified peptide displayed potent anti-inflammation activity in RAW264.7
      cells.

PMID- 22386813
TI  - Ginsenoside Rb1 inhibits osteoclastogenesis by modulating NF-kappaB and MAPKs
      pathways.
AB  - Ginsenosides (GSS), the main active components of ginseng, have been reported
      possessing anti-osteoporosis activity in ovariectomized rats. However, the active
      ingredient and the mechanisms underlying the anti-osteoporosis activity of GSS
      have not been clearly elucidated. In the present study, we determined the effect
      of ginsenoside Rb1, a major component of ginsenosides, on receptor activator of
      NF-kappaB ligand (RANKL)-induced osteoclast formation. Ginsenoside Rb1 inhibited
      RANKL-induced osteoclast differentiation from Raw264.7 cells without
      cytotoxicity. Ginsenoside Rb1 also inhibited RANKL-induced TNFalpha mRNA
      expression in Raw264.7 cells. Pretreatment with ginsenoside Rb1 significantly
      inhibited RANKL-induced the gene expression of c-Fos and nuclear factor of
      activated T-cells c1 (NFATc1), which are two essential and crucial transcription
      factors for osteoclast formation. Rb1 inhibited RANKL-induced nucleus
      translocation and activation of NF-kappaB, the upstream factor of c-Fos and
      NFATc1. Among the three well known mitogen-activated protein kinases (MAPKs), Rb1
      inhibited RANKL-induced JNK and p38 phosphorylation, but not ERK1/2. Taken
      together, our data suggest that ginsenoside Rb1 is one of the effective
      components of GSS for the anti-osteoporosis activity and can inhibit
      osteoclastogenesis by suppressing RANKL-induced activation of both JNK and p38
      MAPKs and NF-kappaB pathways, and consequently down-regulating the gene
      expression of c-Fos and NFATc1 in osteoclast precursors.

PMID- 22386814
TI  - Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs.
AB  - As a late mediator of inflammation, high mobility group box 1 (HMGB1) protein up
      regulates pro-inflammatory cytokines in several inflammatory diseases. Further,
      high plasma levels of HMGB1 correlate with poor prognosis and increased mortality
      in patients with severe inflammation. Oleanolic acid (OA), a triterpenoid known
      for its anti-inflammatory and anti-cancer properties, is commonly present in
      several medicinal plants but the effects of OA on HMGB1-mediated pro-inflammatory
      responses of human endothelial cells is not well-studied. In this study, we
      investigated this question by monitoring the effect of OA on lipopolysaccharide
      (LPS)-mediated release of HMGB1 and the HMGB1-mediated modulation of inflammatory
      responses in human umbilical vein endothelial cells (HUVECs). OA potently
      inhibited the release of HMGB1 by HUVECs as well as down-regulated HMGB1
      dependent adhesion and migration of the monocytic cell line THP-1 to activated
      HUVECs. OA also down-regulated the cell surface expression of the receptor of
      HMGB1, thereby inhibiting HMGB1-dependent pro-inflammatory responses by
      inhibiting activation of nuclear factor-kappaB (NF-kappaB) and production of
      tumor necrosis factor-alpha (TNF-alpha) by HMGB1. Given these results, OA showed
      anti-inflammatory activities and could be a candidate as a therapeutic agent for
      various inflammatory diseases through the inhibition of the HMGB1 signaling
      pathway.

PMID- 22386815
TI  - Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced
      oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2
      antioxidant genes.
AB  - UV radiation from the sun is a potent environmental risk factor in the
      pathogenesis of skin damage. Much of the skin damage caused by ultraviolet A
      (UVA) irradiation from the sun is associated with oxidative stress. The aim of
      this study was to investigate the protective role of ellagic acid (25-75 MUM), a
      natural antioxidant, against UVA (5-20 J/cm(2))-induced oxidative stress and
      apoptosis in human keratinocyte (HaCaT) cells and to reveal the possible
      mechanisms underlying this protective efficacy. Ellagic acid pre-treatment
      markedly increased HaCaT cell viability and suppressed UVA-induced ROS generation
      and MDA formation. Moreover, ellagic acid pre-treatment prevented UVA-induced DNA
      damage as evaluated by the comet assay. Ellagic acid treatment also significantly
      inhibited the UVA-induced apoptosis of HaCaT cells, as measured by a reduction of
      DNA fragmentation, mitochondria dysfunction, ER stress, caspase-3 activation, and
      Bcl-2/Bax deregulation. Notably, the antioxidant potential of ellagic acid was
      directly correlated with the increased expression of HO-1 and SOD, which was
      followed by the downregulation of Keap1 and the augmented nuclear translocation
      and transcriptional activation of Nrf2 with or without UVA irradiation. Nrf2
      knockdown diminished the protective effects of ellagic acid. Therefore, ellagic
      acid may be useful for the treatment of UVA-induced skin damage.

PMID- 22386816
TI  - A 90-day subchronic toxicological assessment of dioscin, a natural steroid
      saponin, in Sprague-Dawley rats.
AB  - Dioscin is the major active compound in many traditional Chinese medicines
      (TCMs), while safety evaluation of this natural product has not yet been
      investigated. Therefore, the aim of this study was to evaluate the 90-day
      subchronic toxicity of dioscin in rats. The rats were divided into four groups
      and dioscin was administered orally at doses of 0, 75, 150 and 300 mg/kg/day,
      respectively. The toxicity of dioscin was evaluated based on clinical
      observations, ophthalmic examination, body weight, food and water consumption,
      urinalysis, hematology, clinical biochemistry and pathology. The results showed
      that dioscin had no subchronic toxicity in female rats and had slight subchronic
      toxicity in male rats. However, male rats in the 300 mg/kg/day group showed
      slight gastro-intestinal tract distension during the treatment period and
      hemolytic anemia in the hematology assessment. Compared with the control group,
      body weight gain was significantly decreased in male rats. Other significant
      changes were not associated with dioscin in the male and female groups. In
      conclusion, the no-observed-adverse-effect level (NOAEL) and the lowest-observed
      adverse-effect level (LOAEL) of dioscin are estimated to be 300 mg/kg/day for
      female and male rats, respectively. Our work provides useful data for further
      research and new drug exploration of dioscin.

PMID- 22386817
TI  - Effects of chitosan oligosaccharides on drug-metabolizing enzymes in rat liver
      and kidneys.
AB  - To investigate the effect of chitosan oligosaccharides (COS) on drug-metabolizing
      enzymes in rat liver and kidneys, male Spraque-Dawley rats were fed a diet
      containing 1% or 3% COS for 5 weeks. The activities of cytochrome P450 (CYP)
      enzymes, UDP-glucurosyltransferase (UGT) and glutathione S-transferase (GST) in
      the liver and kidneys were determined. Significant decreases in microsomal CYP3A
      catalyzed testosterone 6beta-hydroxylation, CYP2C-catalyzed diclofenac 4
      hydroxylation, and CYP4A-catalyzed lauric acid 12-hydroxylation in the liver of
      rats fed the COS diets were observed compared with those rats fed the control
      diet. Immunoblot analyses of CYP proteins showed the same trend as with enzyme
      activities. Increased glutathione content in liver was found in rats fed the 1%
      COS diet. Increased hepatic NADPH: quinone oxidoreductase 1 (NQO1) activity was
      found in rats fed the COS diets. In kidneys, COS had little or no effect on CYP
      enzyme activities. However, increased GST activity was observed in rats fed the
      COS diets. Moreover, a higher UGT activity was found in rats fed the 1% COS diet.
      Our results indicate that COS may suppress hepatic CYP enzymes and induce phase
      II detoxifying reactions in the liver and kidneys of rats.

PMID- 22386818
TI  - Gastroprotective and toxicological evaluation of the Lithothamnion calcareum
      algae.
AB  - Lithothamnion calcareum is a red alga of the Corallinacea family whose main
      feature is the formation of calcium carbonate precipitate in its cell walls. L.
      calcareum is marketed as a nutritional supplement for calcium and other minerals
      in Brazil and other countries under the pharmaceutical name of Vitality 50+. In
      this study, gastroprotective and pre-clinical toxicity assays were performed on
      this product. Doses of 30, 120 and 480 mg/kg were used in the gastroprotective
      study on Wistar rats. A dose of 2000 mg/kg was used in the preclinical acute
      toxicity study and oral doses of 1000 and 2000 mg/kg were used in the subchronic
      toxicity evaluation. L. calcareum played no significant role in the protection of
      the rats' gastric mucosa, nor did it cause increase in gastric irritation. No
      impact on the acute toxicity test was identified. In the subchronic toxicity
      test, serum levels of albumin, total protein and calcium decreased, and
      creatinine levels increased, suggesting hypercalcemia and possible kidney damage
      associated with liver damage, given that the majority of these parameters were
      irreversible. Thus, this work aims to discuss the relationship of the high
      concentration of calcium in the product with the observed effects.

PMID- 22386819
TI  - Removal of trichloroethylene DNAPL trapped in porous media using nanoscale
      zerovalent iron and bimetallic nanoparticles: direct observation and
      quantification.
AB  - Direct trichloroethylene (TCE) dense non-aqueous phase liquid (DNAPL) removal
      inside pore areas using nanoscale zerovalent iron (NZVI) and bimetallic
      nanoparticles were first investigated in a water-saturated porous glass
      micromodel. Effects of nitrate, aqueous ethanol co-solvent, humic substance, and
      elapsed time on TCE DNAPL removal using NZVI were studied by direct
      visualization. The removal efficiency was then quantified by directly measuring
      the remaining TCE DNAPL blobs area using an image analyzer. As ethanol content of
      co-solvent increased, TCE DNAPL removal by NZVI was also increased implying
      sequential TCE DNAPL removal mechanisms: as dissolved TCE was degraded by NZVI,
      TCE dissolution from TCE blobs would be then facilitated and the TCE blob areas
      would be eventually reduced. The presence of nitrate and humic substance hindered
      the NZVI reactivity for the TCE DNAPL removal. In contrast, the TCE DNAPL removal
      efficiency was enhanced using bimetallic nanoparticles in a short-term reaction
      by generating atomic hydrogen for catalytic hydro-dechlorination. However, all
      TCE DNAPL removal efficiencies reached the same level after long-term reaction
      using both NZVI and bimetallic nanoparticles. Direct TCE DNAPL observation
      clearly implied that TCE blobs existed for long time even though all TCE blobs
      were fully exposed to NZVI and bimetallic nanoparticles.

PMID- 22386820
TI  - Utilization of municipal sewage sludge as additives for the production of eco
      cement.
AB  - The effects of using dried sewage sludge as additive on cement property in the
      process of clinker burning were investigated in this paper. The eco-cement
      samples were prepared by adding 0.50-15.0% of dried sewage sludge to unit raw
      meal, and then the mixtures were burned at 1450  degrees C for 2 h. The results
      indicated that the major components in the eco-cement clinkers were similar to
      those in ordinary Portland cement. Although the C(2)S phase formation increased
      with the increase of sewage sludge content, it was also found that the
      microstructure of the mixture containing 15.0% sewage sludge in raw meal was
      significantly different and that a larger amount of pores were distributed in the
      clinker. Moreover, all the eco-cement pastes had a longer initial setting time
      and final setting time than those of plain cement paste, which increased as the
      sewage sludge content in the raw meal increased. All the eco-cement pastes had
      lower early flexural strengths, which increased as the sewage sludge content
      increased, while the compressive strengths decreased slightly. However, this had
      no significant effect on all the strengths at later stages. Furthermore, the
      leaching concentrations of all the types of eco-cement clinkers met the standard
      of Chinese current regulatory thresholds.

PMID- 22386821
TI  - ORF85 of HearNPV encodes the per os infectivity factor 4 (PIF4) and is essential
      for the formation of the PIF complex.
AB  - ORF85 of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) encodes a homologue
      of the per os infectivity factor 4 (PIF-4) of Autographa californica multiple
      nucleocapsid nucleopolyhedrovirus (AcMNPV). In this paper, the functions of HA85,
      particularly in relation to oral infection and interactions with other PIFs were
      investigated. An ha85-disrupted recombinant HearNPV was generated and resulted in
      a complete loss of oral infectivity. Western blotting and co-immunoprecipitation
      (Co-IP) analyses suggested PIF1, PIF2, and PIF3 assemble into a PIF complex in
      HearNPV ODV. Although Western blotting and Co-IP did not show that HA85 is
      associated with the PIF complex, further analysis revealed the inactivation of
      ha85 led to the disruption of PIF complex. Yeast two hybridization analyses
      revealed that HA85 interacts with P74, PIF1, PIF2 and PIF3. In conclusion, HA85
      is identified as the PIF4 of HearNPV and is proposed to participate in the
      formation of HearNPV PIF complex via associations with other PIFs.

PMID- 22386822
TI  - Structure-function relations in the NTPase domain of the antiviral tRNA ribotoxin
      Escherichia coli PrrC.
AB  - Breakage of tRNA by Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies
      a host antiviral response to phage T4 infection. Expression of EcoPrrC is
      cytocidal in yeast, signifying that PrrC ribotoxicity crosses phylogenetic domain
      boundaries. EcoPrrC consists of an N-terminal NTPase module that resembles ABC
      transporters and a C-terminal nuclease module that is sui generis. PrrC homologs
      are prevalent in many other bacteria. Here we report that Haemophilus influenzae
      PrrC is toxic in E. coli and yeast. To illuminate structure-activity relations,
      we conducted a new round of mutational analysis of EcoPrrC guided by primary
      structure conservation among toxic PrrC homologs. We indentify 17 candidate
      active site residues in the NTPase module that are essential for toxicity in
      yeast when EcoPrrC is expressed at high gene dosage. Their functions could be
      educed by integrating mutational data with the atomic structure of the transition
      state complex of a homologous ABC protein.

PMID- 22386823
TI  - Overview of microbicides for the prevention of human immunodeficiency virus.
AB  - Human immunodeficiency virus (HIV) prevention tools that women can use and
      control are urgently needed. Microbicides are chemical products applied to the
      vagina or rectum to prevent the sexual transmission of HIV. Four classes of
      candidate microbicides have been tested to date: those that (1) enhance the
      natural defences in the vagina to inactivate HIV; (2) inactivate HIV in the
      vagina; (3) prevent HIV from attaching to, and fusing with, the host cells; and
      (4) prevent HIV from replicating in genital tract host cells. Despite numerous
      disappointing efficacy trial results over the past 20 years, substantial progress
      is now being made in microbicide development after the release of the CAPRISA 004
      trial, which provided proof-of-concept that topical antiretroviral microbicides
      can prevent sexual transmission of HIV and herpes simplex type-2 infection.
      Microbicides, which fill an important gap for women-controlled prevention
      methods, have the potential to alter the course of the HIV pandemic.

PMID- 22386824
TI  - Clinical challenges in a patient with dabigatran-induced fatal hemorrhage.
AB  - OBJECTIVE: To report clinical challenges in managing dabigatran-induced bleeding.
      METHODS: A 78-year-old woman came to the hospital with severe coagulopathy,
      respiratory failure, hypotension, and bleeding secondary to dabigatran therapy.
      At admission, creatinine clearance was 15 mL/min; prothrombin time, 147.5
      seconds; activated partial thromboplastin time, >200 seconds; and international
      normalized ratio, 12.42. Medications taken at home included dabigatran, 150 mg
      BID. During the hospitalization, multiple blood product transfusions were given,
      vitamin K and prothrombin complex concentrate were administered, and dialysis was
      initiated in an attempt to achieve hemostasis. Despite multiple interventions,
      coagulopathy persisted (prothrombin time, 70.8 seconds; activated partial
      thromboplastin time, >200 seconds; and international normalized ratio, 6.05),
      with continued bleeding. On hospital day 5, the patient died. CONCLUSIONS:
      According to the Naranjo probability scale, bleeding associated with dabigatran
      revealed a probable relationship. This fatal case illustrates our concern about
      the usefulness of currently recommended anticoagulation laboratory tests and of
      the efficacy of blood transfusion, dialysis, and prothrombin complex concentrate
      in managing life-threatening bleeding secondary to dabigatran. In addition,
      clinicians should be cognizant of the renal recommendations for the newer oral
      anticoagulant agents to prevent potentially catastrophic results.

PMID- 22386825
TI  - Prevalence and progression of peripheral vascular calcification in type 2
      diabetes subjects with preserved kidney function.
AB  - AIMS: To determine predictors of prevalence and progression of peripheral
      vascular calcification (VC) in type 2 diabetes (DM) subjects with preserved
      kidney function. METHODS: Fifty-eight subjects (age 63 +/- 11.6 years) with type
      2 DM and serum creatinine <125 MUmol/l were studied. A CT scan of femoral,
      posterior tibial and dorsalis pedis arteries was carried out at baseline and at
      one year. Serum osteoprotegerin (OPG) and RANKL were measured along with routine
      biochemistry. RESULTS: Seventy-eight percent of patients had baseline VC, 47%
      with femoral VC, 49% with VC at two sites - femoral and foot, and 4% foot VC
      alone. Age, ethnicity, peripheral neuropathy and eGFR were independent predictors
      of baseline VC. Baseline calcification was the most important predictor of VC
      progression and was present in all subjects with progression compared to 35% of
      non-progressors (p < 0.001). Exclusion of demographic factors from models
      revealed neuropathy and serum OPG levels as independent predictors of both;
      baseline VC and progression. CONCLUSIONS: Subjects with type 2 DM and well
      preserved renal function had a high prevalence of VC, which was rapidly
      progressive especially in those with baseline VC. Age, ethnicity, neuropathy,
      smoking and eGFR were predictors of baseline VC and progression.

PMID- 22386826
TI  - Comparison of fasting bioavailability among 100-mg commercial, 100-mg generic,
      and 50-mg chewable generic sildenafil tablets in healthy male Mexican volunteers:
      a single-dose, 3-period, crossover study.
AB  - BACKGROUND: Sildenafil citrate (SIL) was the first oral drug registered in Mexico
      for the treatment of erectile dysfunction. However, succinct pharmacokinetic data
      are available in the Mexican population. OBJECTIVE: The goals of the present work
      were: (1) to design a specific method to quantify SIL plasma levels by using UPLC
      MS/MS; (2) to compare oral SIL bioavailability in Mexican men with
      pharmacokinetic data in other populations; (3) to fulfill local regulatory
      requests; and (4) to describe the relative tolerability of a new 50-mg chewable
      tablet. METHODS: This was a randomized, single-dose, 3-period, 6-sequence
      crossover study in healthy male volunteers. In each period, subjects received
      single oral doses of 100 mg of sildenafil (1 commercial [reference(*)], 1 generic
      [test 1(?)], or 2 chewable generic tablets [test 2(?)]), with a 4-day washout
      period between each dose. Serial blood samples were collected for up to 24 hours.
      SIL was measured in heparinized plasma by using a validated UPLC-MS/MS method.
      Pharmacokinetic parameters included C(max), T(max), AUC(0-24), and AUC(0
      infinity). Bioequivalence was established if 90% CIs for mean test:reference
      ratios of log-transformed C(max) and AUC fell within the range of 0.80 to 1.25.
      Tolerability was assessed on the basis of a clinical interview with the subject
      and monitoring of vital signs. RESULTS: Demographic data showed a homogeneous
      population. Validation of analytical method proved to be linear within the range
      of 1 to 1000 ng/mL, with selectivity, accuracy, and precision. 90% CIs for test
      1:reference ratios were 86.52 to 113.56, 94.75 to 108.84, and 94.97 to 108.82 for
      the logarithm parameters C(max), AUC(0-24), and AUC(0-infinity), respectively.
      The 90% CIs for the test 2:reference ratios were 82.14 to 107.24, 98.26 to
      112.56, and 99.19 to 113.34 for C(max), AUC(0-24), and AUC(0-infinity). Regarding
      relative tolerability, slight cephalea was the most common adverse effect.
      CONCLUSIONS: The developed analytical method was validated in compliance with
      local requirements and was useful for sildenafil measurement. This single-dose
      study under fasting conditions suggests that both test products met the Mexican
      regulatory criteria for assuming bioequivalence in these healthy, male Mexican
      volunteers. The clinical data suggest that the chewable tablets were well
      tolerated by volunteers.

PMID- 22386828
TI  - A retrospective database analysis of neuropathic pain and oral antidiabetic
      medication use and adherence among Texas adults with type 2 diabetes enrolled in
      Medicaid.
AB  - BACKGROUND: Adherence to oral antidiabetic (OAD) medications is essential in
      achieving glycemic control and slowing the progression of diabeties-related
      complications such as neuropathic pain. OAD medication adherence has been
      suboptimal and adding neuropathic pain medications may negatively affect
      adherence. However, little is known about adherence to neuropathic pain
      medications by patients with diabetes and how this may be related to OAD
      medication adherence. OBJECTIVE: The objectives of our study were to: (1)
      describe painful diabetic peripheral neuropathy (PDPN) and OAD medication use,
      (2) determine if PDPN medication adherence differs among individual PDPN
      medications (ie, tricyclic antidepressants, gabapentin, pregabalin, and
      duloxetine); and (3) determine if PDPN medication adherence is related to post
      index OAD medication adherence while controlling for covariates. METHODS: This
      retrospective prescription claims database study included continuously enrolled
      Texas Medicaid beneficiaries who were adult (aged 30-64 years) prescribed OAD
      (pre- and post-index) and PDPN (post-index) medications. Data were extracted from
      June 1, 2003 to October 31, 2009. The main study outcome was post-index OAD
      medication adherence. Primary independent variables included PDPN medication
      adherence and PDPN medication type. Demographic and medication use
      characteristics served as covariates. Adherence was measured both continuously
      and dichotomously (80% cut-off) using medication possession ratio (MPR). RESULTS:
      The sample's (n = 4277) overall mean MPR (SD) for PDPN medications was 75.4%
      (23.9%). Mean MPR differed significantly among individual PDPN medications (P <
      0.0001) and was highest for duloxetine (85.6% [18.2%]) and lowest for pregabalin
      (69.4% [24.9%]). Overall mean MPR (SD) for OAD medications decreased
      significantly (P < 0.0001) from 73.0% (24.3%) in the pre-index period to 64.5%
      (25.6%) in the post-index period. After controlling for covariates, nonadherers
      (ie, MPR <80%) to PDPN medications, compared with adherers (ie, MPR >=80%), were
      significantly less likely to be adherent to OAD medications in the post-index
      period (odds ratio = 0.626; 95% CI, 0.545-0.719). CONCLUSIONS: Overall, these
      data suggest that mean adherence to both PDPN and OAD medications was suboptimal
      (MPR <80%). Patients who were adherent to PDPN medications were more adherent to
      OAD medications in the post-index period, but OAD medication adherence was
      independent of the type of PDPN medication used. OAD adherence decreased from pre
      to post-index (ie, when patients were prescribed PDPN medications), which may
      indicate an opportunity for practitioners to emphasize the importance of OAD
      adherence in reducing the progression to neuropathy.

PMID- 22386830
TI  - Hereditary angioedema therapies in the United States: movement toward an
      international treatment consensus.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare, potentially life-threatening
      autosomal dominant disease characterized by recurrent angioedema attacks that
      affect the skin, gastrointestinal tract, and airway, including the larynx.
      Pharmacologic developments in HAE treatment have culminated in the recent
      introduction of 4 new HAE-specific therapies in the United States. OBJECTIVES: In
      light of these new therapeutic options, this commentary outlines historical US
      HAE therapy choices, discusses the potential effect of the 4 recently approved
      HAE treatments, and considers strategies for optimizing their use in line with
      international treatment recommendations. DISCUSSION: Treatment options for HAE in
      the United States have been limited to attenuated androgens and antifibrinolytic
      agents for long-term prophylaxis and FFP and supportive therapy for the
      management of acute attacks. The 4 new therapies that have recently become
      available (ie, 2 plasma-derived C1 esterase inhibitor (C1-INH) concentrates, the
      kallikrein inhibitor ecallantide, and the bradykinin beta(2)-antagonist
      icatibant) have provided an opportunity to change routine HAE treatment. In 2009,
      despite the availability of 2 of the new treatments (ie, the plasma-derived C1
      INH concentrates), a large survey of US physicians suggested that wide
      variability still existed in the treatment of patients with HAE. Since this
      survey was undertaken, clinical experience with all 4 new treatments has
      increased significantly, and because 3 of these agents (ie, 2 plasma-derived C1
      INH concentrates and icatibant) can be self-administered by trained patients,
      physicians can now provide individualized care that is proven effective and more
      aligned with international guidance.

PMID- 22386829
TI  - Single-pill combination of telmisartan/amlodipine versus amlodipine monotherapy
      in diabetic hypertensive patients: an 8-week randomized, parallel-group, double
      blind trial.
AB  - BACKGROUND: Hypertensive patients with diabetes often require combination therapy
      to achieve a blood pressure (BP) goal, and evidence suggests that time to BP goal
      is crucial to decrease cardiovascular risk. OBJECTIVE: The aim of the study was
      to investigate whether the single-pill combination of telmisartan and amlodipine
      was superior to amlodipine alone as initial antihypertensive therapy in patients
      with diabetes and hypertension. METHODS: An 8-week, randomized, parallel-group,
      double-blind international trial comparing the once-daily single-pill combination
      of telmisartan 80 mg and amlodipine 10 mg (T/A; n = 352) with once-daily
      amlodipine 10 mg (A; n = 354) in patients with type 2 diabetes mellitus and stage
      1 or 2 hypertension (systolic BP [SBP] >150 mm Hg). RESULTS: Patient demographics
      were similar between treatment groups, with an mean (SD) age of 60.5 (10.1)
      years; 51.7% were male, the mean (SD) body mass index was 32.0 (6.1) and the mean
      (SD) duration of hypertension was 8.8 (7.9) years. After 8 weeks (primary end
      point) as well as after 1, 2, and 4 weeks (key secondary end points),
      significantly greater decreases in the in-clinic mean seated trough cuff SBP with
      T/A versus A were achieved (-29.0 mm Hg vs -22.9 mm Hg at 8 weeks; P < 0.0001).
      After 8 weeks, 71.4% versus 53.8% of patients achieved the BP goal (<140/90 mm
      Hg) with T/A versus A, with mean SBPs of 131.9 and 137.9 mm Hg, respectively.
      Similar results were observed in the obese (metabolic syndrome) subpopulation.
      The more stringent goal (<130/80 mm Hg) was achieved by 36.4% and 17.9% patients
      in the T/A and A groups, respectively. The most common adverse events were
      peripheral edema, headache, and dizziness. CONCLUSIONS: In this selected
      population of patients with diabetes and hypertension, T/A provided prompt and
      greater BP decreases compared with A monotherapy, with the majority of patients
      achieving the BP goal (<140/90 mm Hg).

PMID- 22386831
TI  - The APC and PreSAP trials: a post hoc noninferiority analysis using a
      comprehensive new measure for gastrointestinal tract injury in 2 randomized,
      double-blind studies comparing celecoxib and placebo.
AB  - BACKGROUND: Previous gastrointestinal (GI) outcomes of nonsteroidal anti
      inflammatory drug (NSAID) trials have focused on upper GI events, although recent
      evidence suggests NSAID-related lower GI effects are important and clinically
      relevant. OBJECTIVE: We assessed the long-term GI adverse event (AE) profile of
      celecoxib in a nonarthritis population. The aim of this post hoc analysis was to
      determine the incidence of serious GI AEs, using a new Clinically Significant
      Upper and/or Lower GI Events end point. METHODS: Patients from 2 colorectal
      adenoma recurrence studies were included. Patients received celecoxib 200 mg/400
      mg BID, 400 mg once daily, or placebo over 3 years. The analysis measured
      noninferiority, using a prespecified definition of noninferiority. Celecoxib was
      predefined to be noninferior to placebo if the upper limit of the 95% CI for the
      hazard ratio (HR) with celecoxib was <1.25, at any dose, compared with the
      placebo (calculated using the Cox proportional hazards model). RESULTS: A total
      of 3588 patients were included; in the primary analysis, the HR for celecoxib
      (any dose) compared with placebo was 1.22 (95% CI: 0.69-2.18; P = 0.4948). In the
      secondary dose analyses, the HR associated with a 400-mg daily dose, compared
      with placebo, was 1.04 (95% CI: 0.55-1.96; P = 0.9149); for 800 mg/d, the HR was
      1.79 (95% CI: 0.82-3.89; P = 0.1427). In a third covariate analysis, low-dose
      aspirin use (HR = 2.33; 95% CI: 1.33-4.08) and age >=65 years (HR = 1.82; 95% CI,
      1.05-3.15) was suggested to have a statistically significant association with
      increased risk of GI AEs. Study limitations include retrospective evaluation and
      small sample size of patients with GI AEs. CONCLUSIONS: The noninferiority of
      celecoxib to placebo was not established because the HR for the time to the first
      Clinically Significant Upper and/or Lower GI Event was greater than the
      prespecified upper limit of 95% CI for noninferiority. In addition, HRs
      associated with daily doses of 400 or 800 mg celecoxib compared with placebo were
      not significant. However, a significantly increased risk of clinically
      significant upper and/or lower GI events was observed in low-dose aspirin users
      (<=162.5 mg average daily use) and in patients >=65 years of age.

PMID- 22386832
TI  - Benign myoclonic epilepsy in infancy with preceding afebrile generalized tonic
      clonic seizures in Japan.
AB  - Benign myoclonic epilepsy in infancy (BMEI) is the youngest form of idiopathic
      generalized epilepsy, characterized by myoclonic seizures (MS) in the first three
      years of life in otherwise normal infants, and the lack of other seizure types
      except for rare simple febrile seizures. Although afebrile generalized tonic
      clonic seizures (GTCS) have been described to develop later in the clinical
      course of BMEI, mostly during adolescence, an association with GTCS in the early
      stage of BMEI has never been recognized. We herein report seven children who
      satisfied the criteria of BMEI except for the recurrence of GTCS before the onset
      of MS. The age of onset and ictal video-polygraphic features of MS, as well as
      the long-term seizure and developmental outcome in these children were similar to
      those of children with typical BMEI. Furthermore, these GTCS mostly disappeared
      within several months and were replaced by MS. Our study indicates that these
      children may constitute a BMEI subgroup, expanding the spectrum of BMEI.

PMID- 22386833
TI  - Advanced glycation end-products induce injury to pancreatic beta cells through
      oxidative stress.
AB  - AIM: This study evaluated the direct effects of advanced glycation end-products
      (AGEs) on pancreatic beta cells, including cellular viability, generation of
      reactive oxygen species (ROS) and insulin secretion, and also looked for the main
      source of ROS in INS-1 cells and the possible molecular mechanism(s) of cell
      injury by AGEs. METHODS: INS-1 cells were cultured with 100, 200 and 500 mg/L of
      AGEs for specific periods of time. Cell apoptosis was determined by ELISA and
      real-time PCR assays. ROS were detected by DCFH-DA and MitoSOX Red probes with a
      flow cytometer, NADPH oxidase activity was measured by lucigenin
      chemiluminescence and MAPK phosphorylation was measured by Western blot tests.
      RESULTS: Both cell apoptosis and ROS generation increased in AGE-treated cells in
      a dose-dependent way, and both the mitochondrial electron transport chain and
      NADPH oxidase pathway participated in ROS generation, although the role of the
      mitochondrial pathway was earlier and more important. AGEs exerted a toxic effect
      on insulin secretion that could be largely reversed by inhibiting ROS.
      CONCLUSION: AGEs injured INS-1 cells by oxidative stress mainly through the
      mitochondrial pathway, although the JNK and p38 MAPK signaling pathways were also
      key modulators in ROS-mediated beta-cell death.

PMID- 22386834
TI  - A study of the 3-year incidence of diabetic retinopathy in a French diabetic
      population seen at Lariboisiere Hospital, Paris.
AB  - AIM: This study evaluated the incidence of diabetic retinopathy (DR) over a 3
      year period in a French population that was followed by OPHDIAT(r), and assessed
      the clinical and biological risk factors associated with incident retinopathy.
      METHODS: The studied patients were screened for DR during hospitalization for
      their annual diabetes check-up in the endocrinology department by two
      examinations three years apart. DR screening used the OPHDIAT(r) telemedical
      network, and the examination included clinical and biological data. RESULTS: A
      total of 254 patients were studied. At the 3-year follow-up, the incidence was
      14.0%, (CI: 9.5-18.4%). Longer duration of diabetes and the presence of micro- or
      macroalbuminuria were significantly associated with incident retinopathy
      (P<0.05). Other potential risk factors were not statistically significantly
      related to DR progression, and only treatment with insulin showed a trend towards
      significance (P<0.20). CONCLUSION: This study provides the first French data on
      the incidence of DR, which was estimated after a 3-year follow-up at 14.0%.
      Longer duration of time from the onset of diabetes and higher baseline
      albuminuria were the only statistically significant risk factors found for the
      incidence of DR after our 3-year study. Nevertheless, microalbuminuria should be
      more widely used in ophthalmological practice in the assessment of DR, as is
      already the case for both blood pressure and HbA(1c).

PMID- 22386835
TI  - Physical-activity prescription for obesity management in primary care: attitudes
      and practices of GPs in a southern French city.
AB  - AIM: The study documented the attitudes and practices of French general
      practitioners (GPs) regarding the prescription of physical activity (PA) for
      obesity management. METHODS: A cross-sectional survey of all 254GPs with
      practices in a city in the south of France was performed, of which 203 (80%)
      questionnaires were returned. From these, demographic, professional and personal
      data, beliefs, attitudes, training and barriers to prescribing PA were assessed.
      RESULTS: GPs are very much aware of the importance of PA in the management of
      obesity, as 94% reportedly prescribed it frequently ('usually' or 'often').
      However, only a minority recommended PA levels that were consistent with most
      guidelines. Even though most of the GPs (71%) reported a lack of training in
      prescribing PA, only a slight majority (52%) wished to undergo such training.
      Patients' non-compliance was the main obstacle for 63% of the GPs. Also, although
      only 1% of the GPs used software and Internet resources, 62% expressed a desire
      to incorporate these tools in their practices. The personal characteristics of
      GPs also influenced their attitudes and practices, as reflected by the fact that
      overweight or obese GPs favoured psychobehavioural management rather than PA
      (P=0.03). Younger GPs (<45 years) felt less adequately trained than their elders
      (P=0.01) and were more eager for additional training. CONCLUSION: GPs play a
      central role in preventing the pandemic of obesity and other chronic diseases for
      which PA is a cornerstone. However, the need to improve GP practices in
      prescribing PA remains a challenge. Better medical education and the development
      of adequate Web-based tools should also be prioritized.

PMID- 22386836
TI  - After three randomised controlled trials comparing 120-W high-performance-system
      potassium-titanyl-phosphate laser vaporisation to transurethral resection of the
      prostate (TURP), is this procedure finally first-line, outdated, or still not
      surpassing TURP?

PMID- 22386837
TI  - The genetic basis of kidney cancer: implications for management and use of
      targeted therapeutic approaches.

PMID- 22386839
TI  - High-risk prostate cancer: from definition to contemporary management.
AB  - CONTEXT: High-risk prostate cancer (PCa) is a potentially lethal disease. It is
      clinically important to identify patients with high-risk PCa early on because
      they stand to benefit the most from curative therapy. Because of recent advances
      in PCa management, a multimodal approach may be advantageous. OBJECTIVE: Define
      high-risk PCa, and identify the best diagnostic and treatment patterns for
      patients with clinically localized and locally advanced disease. A critical
      analysis of published results following monomodal and/or multimodal therapy for
      high-risk PCa patients was also performed. EVIDENCE ACQUISITION: A review of the
      literature was performed using the Medline, Embase, Scopus, and Web of Science
      databases as well as the Cochrane Database of Systematic Reviews. EVIDENCE
      SYNTHESIS: High-risk PCa accounts for <= 15% of all new diagnoses. Compared with
      patients with low- and intermediate-risk PCa, patients with high-risk PCa are at
      increased risk of treatment failure. Unfortunately, no contemporary randomized
      controlled trials comparing different treatment modalities exist. Evaluation of
      the results published to date shows that no single treatment can be universally
      recommended. Most often, a multimodal approach is warranted to optimize patient
      outcomes. CONCLUSIONS: A significant minority of patients continue to present
      with high-risk PCa, which remains lethal in some cases. Outcomes following
      treatment of men with high-risk tumors have not substantially improved over time.
      However, not all high-risk patients are at the same risk of PCa progression and
      death. At present, a multimodal approach seems the best way to achieve acceptable
      outcomes for high-risk PCa patients.

PMID- 22386840
TI  - Pulmonary rehabilitation following radical chemo-radiation in locally advanced
      non surgical NSCLC: Preliminary evidences.

PMID- 22386841
TI  - Risks of adverse pregnancy outcome in endometriosis.
AB  - Bleeding from endometriotic implants is now an established cause of acute
      hemoperitoneum in pregnancy. However, the adverse impact of pelvic endometriosis
      on uterine function before conception may also interfere with subsequent deep
      placentation, accounting for the increased risk of obstetrical complications,
      including preterm birth and antepartum hemorrhage.

PMID- 22386842
TI  - Anti-ACTL7a antibodies: a cause of infertility.
AB  - OBJECTIVE: To show that antibodies against ACTL7a, a spermatozoon-specific
      protein, may be a cause of immunologic infertility. DESIGN: Determine the
      presence of anti-ACTL7a antibodies in infertile blood, raise antibodies against
      ACTL7a in rabbits, and demonstrate that the in vitro treatment of mouse
      spermatozoa with infertile sera markedly reduces their fertilizing capacity.
      Demonstrate that the active immunization of mice with ACTL7a protein reduces
      fertility. SETTING: National Research Institute for Family Planning, Beijing,
      World Health Organization Collaboration Center of Human Reproduction, China.
      ANIMAL(S): Rabbits, ICR mice. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Mass spectrometry, indirect immunostaining, spermatozoa agglutination test, and
      standard fertility assay. RESULT(S): The fertilizing potential of mouse
      spermatozoa was markedly reduced after in vitro treatment with ACTL7a antibody
      containing serum from a vasectomized man. Active immunization with ACTL7a
      significantly reduced the fertility of mice. Anti-ACTL7a antibodies caused the
      agglutination of mouse and human spermatozoa in vitro. Furthermore, the
      antibodies were detected in the sera of additional vasectomized men.
      CONCLUSION(S): Anti-ACTL7a antibodies may cause infertility in mice because the
      in vitro treatment of mouse spermatozoa with ACTL7a antibody-containing serum
      markedly reduced the fertilizing potential of the spermatozoa. In addition, the
      active immunization of mice with ACTL7a resulted in significant reductions in
      fertility.

PMID- 22386843
TI  - DNA integrity is maintained after freeze-drying of human spermatozoa.
AB  - OBJECTIVE: To evaluate the effects on human spermatozoa of freeze-drying, also
      known as lyophilization, and of cryopreservation in liquid nitrogen. DESIGN:
      Prospective experimental study. SETTING: Reproductive medicine unit and a private
      IVF center. PATIENT(S): Thirty healthy male donors. INTERVENTION(S): Sperm
      samples from 30 donors divided as two aliquots, one to be lyophilized and the
      other to be cryopreserved in liquid nitrogen. MAIN OUTCOME MEASURE(S): Assessment
      of count, motility, morphology, viability, DNA integrity, chromosomal status, and
      birefringence properties of lyophilized and cryopreserved human spermatozoa
      compared with the same parameters in the fresh sample. RESULT(S): Although sperm
      viability and motility were totally compromised after freeze-drying, the sperm
      chromatin structure was not altered in comparison with fresh samples, which
      demonstrated that the procedure did not affect DNA integrity. The sperm-head
      inner protoplasmic structures were also preserved, which was estimated by
      assessing the corresponding birefringence characteristics. After cryopreservation
      with liquid nitrogen, the motility, viability, and DNA integrity of spermatozoa
      were statistically significantly reduced compared with the fresh samples; the
      proportion of sperm cells with abnormal head birefringence increased
      meaningfully. CONCLUSION(S): The process of freeze-drying deeply damages cell
      membranes; however, unlike with liquid nitrogen preservation, it does not affect
      DNA integrity.

PMID- 22386844
TI  - A persistent misperception: assisted reproductive technology can reverse the
      "aged biological clock".
AB  - Delaying motherhood should be a free choice made in full knowledge of all the
      consequences, but modern women have alarming misconceptions about their own
      reproductive systems and the effectiveness of assisted reproductive technologies.
      Doctors and health professionals must begin to discuss fertility preservation
      with their patients and make sure that young women truly understand all their
      options. Preventing age-related infertility is the responsibility not only of
      doctors and medical practitioners but also of society at large. Social, economic,
      and personal pressures are causing women to decide to conceive later in life, yet
      those who choose to delay motherhood are stigmatized as being selfish and
      unconcerned about starting a family. This stigma must be banished, and age
      related infertility should be faced as a medical problem.

PMID- 22386845
TI  - [Prenatal intestinal volvulus: A life-threatening event with good long-term
      outcome].
AB  - BACKGROUND AND AIMS: To describe the outcome of neonates with prenatal intestinal
      volvulus. PATIENTS AND METHODS: All neonates with prenatal intestinal volvulus
      managed in our institution between May 2004 and December 2010 were
      retrospectively studied. All neonates with prenatal or neonatal diagnosis of
      prenatal intestinal volvulus were included. We analyzed age at diagnosis, fetal
      ultrasound (US) scan and magnetic resonance imaging (MRI) findings, clinical
      signs at birth, surgical findings, management, and postoperative outcome.
      RESULTS: Ten neonates with prenatal intestinal volvulus were identified. Prenatal
      US scans or MRI demonstrated evidence of meconium peritonitis in one fetus and
      bowel dilatation in 2 others. The mean gestational age at birth was 36 weeks
      (range, 31-38 weeks) and the mean birth weight was 2811g (range, 2050-3700g). One
      premature neonate developed respiratory distress and required ventilatory support
      at birth. In 7 neonates, clinical examination showed distended abdomen and
      emesis, whereas plain abdominal radiographs showed intestinal obstruction. All
      neonates underwent surgery and all had normal intestinal rotation, except one
      with total intestinal volvulus secondary to malrotation. Other causes of volvulus
      were suspected in 4 neonates: mesenteric defect (n=1), intestinal atresia (n=2)
      and narrow mesentery (n=1). Detorsion of total volvulus, ileostomy, or intestinal
      resection with primary anastomosis was performed in 2, 5, and 3 neonates,
      respectively. One patient with total intestinal volvulus secondary to malrotation
      died, whereas all other neonates survived. In one patient, the postoperative
      course was complicated by intestinal dysmotility of the distal small bowel
      requiring a secondary jejunoileostomy. Stoma closure was subsequently performed
      at 1 year of age with good outcome. One patient developed angiocholitis treated
      successfully with antibiotics. Median time to initiate enteral feeds was 7 days
      (range, 4-16 days) and all patients were subsequently weaned from parenteral
      nutrition. Median duration of parenteral nutrition was 29 days (range, 6-667
      days). None of the patients had cystic fibrosis. Unlike postnatal volvulus, most
      prenatal volvulus occurs without malrotation. Although prenatal volvulus is a
      life-threatening condition, our results suggest that good long-term outcome can
      be achieved in most cases.

PMID- 22386846
TI  - [Progress and disappointments in French neonatal medicine].

PMID- 22386847
TI  - Is the angioimmunoblastic T-Cell lymphoma beneficial to avoid CD4(+) lymphopenia
      and other AIDS manifestations in patients infected with Human Immunodeficiency
      Virus?

PMID- 22386848
TI  - Developing user centred critical care discharge information to support early
      critical illness rehabilitation using the Medical Research Council's complex
      interventions framework.
AB  - OBJECTIVES: This paper reports on an intervention designed during an ongoing two
      phase project aimed at improving early critical illness rehabilitation. It
      focuses specifically on the justification for a newly developed critical care
      discharge information pack: 'User Centred Critical Care Discharge Information
      Pack' (UCCDIP). The intervention is described in detail and the chosen research
      methods are discussed. BACKGROUND: Discharge from critical care to a ward is a
      difficult time for patients and relatives. Research suggests that effective
      information has the potential to reduce relocation stress and optimise recovery.
      METHODS: Using the Medical Research Council framework for the development and
      evaluation of complex interventions, a phase I focus group study and
      collaboration with service users/carers informed the development of a new
      critical care discharge information pack, currently being evaluated in a phase II
      Randomised Controlled Trial. CONCLUSION: UCCDIP acknowledges the patients' need
      to understand what they have been through and the progress they have made. It
      provides for the different information needs of patients and relatives,
      recognising their physical and psychological vulnerability. Through its use of
      reflection and participation, UCCDIP has the potential to optimise support of
      adult patients and their families during early critical illness rehabilitation.

PMID- 22386849
TI  - Acadl-SNP based genotyping assay for long-chain acyl-CoA dehydrogenase deficient
      mice.
AB  - The long-chain acyl-CoA dehydrogenase (LCAD) (Acadl=gene; LCAD=protein) deficient
      mouse model has been important in evaluating the role of mitochondrial fatty acid
      oxidation of long-chain fatty acids in metabolic disorders. The insertion vector
      based gene targeting strategy used to generate this model has made it difficult
      to distinguish homozygous and heterozygous genotypes containing targeted Acadl
      alleles in LCAD-deficient mice. Herein, we describe the design and validation of
      Acadl SNP genotyping methods capable of distinguishing between heterozygous and
      homozygous LCAD-deficient mice. The Acadl SNP genotyping assays are effective at
      allelic discrimination of both C57BL/6 and 129 mouse strain-based Acadl alleles
      under conditions including, both low purity and quantity genomic DNA templates.
      This makes the method practical and provides the necessary tools for genotyping
      the LCAD-deficient mouse model.

PMID- 22386850
TI  - Genetic diversity of community-associated methicillin-resistant Staphylococcus
      aureus isolated from Tenerife Island, Spain.
AB  - With the recent detection of MRSA (methicillin-resistant Staphylococcus aureus)
      infections in patients lacking health care-related risk factors, the term
      community-acquired MRSA (CA-MRSA) has been become widely recognised. Many cases
      of CA-MRSA spreading to the community have been described worldwide. The aim of
      this study was to determine the features of CA-MRSA isolates from Tenerife
      Island. Toward this end, one hundred MRSA isolates were collected from eight
      different health regions, and their molecular features were investigated. This
      study revealed a wide variety of MRSA clones, including an emergent ST: ST1434
      (CC8) and two new spa types, t7575 (ST125) and t7678 (ST22). The PVL genes were
      found in only five isolates belonging to unrelated lineages, ST8, ST30 and ST22,
      which could indicate at least three independent introductions of PVL(+) strains
      to Tenerife. Moreover, we detected that hospital MRSA clones, like EMRSA-15 and
      EMRSA-16, had spread to the community and are now circulating in both
      environments. Therefore, in our study, the CDC's rules were not specific enough
      to distinguish CA-MRSA from HA-MRSA. Thus, we think that the current
      epidemiological information is not enough to discriminate between both MRSAs, and
      it is necessary for prevention guidelines to include the routine determination of
      at least the genetic background, the antimicrobial susceptibility profile, and
      the PVL genes of each MRSA isolate.

PMID- 22386851
TI  - Characterization of cofactor-independent phosphoglycerate mutase isoform-1 (Wb
      iPGM) gene: a drug and diagnostic target from human lymphatic filarial parasite,
      Wuchereria bancrofti.
AB  - The inter-conversion of 3-phosphoglycerate and 2-phosphoglycerate during
      glycolysis and gluconeogenesis in filarial nematodes, is catalyzed by a co-factor
      independent phosphoglycerate mutase (iPGM). The gene encoding iPGM isoform-1 was
      amplified from Wuchereria bancrofti, the major causative agent of human lymphatic
      filariasis. Partial genomic DNA (gDNA) fragment of the gene was also amplified
      from periodic and sub-periodic forms of W. bancrofti and Brugia malayi and
      sequenced. The Wb-iPGM isoform-1 gene encodes an ORF of 515 amino acids and is
      found to share 99.4%, 96.0%, and 64.0% amino acid sequence identity with iPGM of
      B. malayi, Onchocerca volvulus, and Caenorhabditis elegans, respectively. Serine
      and all the other 13 amino acid residues involved in the catalytic function of
      iPGM are highly conserved. Further comparison of iPGM nucleotide and amino acid
      sequences of Wolbachia of B. malayi with Wb-iPGM showed 41% and 54.4% similarity,
      respectively. The analysis of partial genomic and amino acid sequences and
      phylogenetic tree of Wb-iPGM indicated that this gene, apart from being a
      potential drug target, could provide diagnostic, taxonomical, and evolutionary
      markers. This is the first report of the characterization of iPGM gene from W.
      bancrofti.

PMID- 22386852
TI  - Morphometric and molecular characterization of the series Guyanensis (Diptera,
      Psychodidae, Psychodopygus) from the Ecuadorian Amazon Basin with description of
      a new species.
AB  - Several populations of the series Guyanensis (Diptera, Psychodidae,
      Psychodopygus) were collected from the Yasuni National Park in the Ecuadorian
      Amazon region. The specimens comprised the species Psychodopygus geniculatus,
      Psychodopygus luisleoni and Psychodopygus corossoniensis. Within Ps. geniculatus,
      we observed two populations, one with a narrow paramere and relatively short
      genital filaments and the other characterized by a wider coxite and longer
      genital filaments. A multiple approach combining morphology, morphometry and DNA
      sequencing of the ribosomal internal transcribed spacer 2 (ITS2) and the
      mitochondrial cytochrome b gene was carried out. Morphological, morphometric and
      molecular data strongly suggested the presence of two populations within Ps.
      geniculatus. The lack of intermediate forms within these populations supported
      the proposal of two sympatric species. This report describes Psychodopygus
      francoisleponti n. sp.

PMID- 22386853
TI  - pH-dependent entry of chikungunya virus into Aedes albopictus cells.
AB  - BACKGROUND: The chikungunya virus (CHIKV) recently caused explosive outbreaks in
      Indian Ocean islands and India. During these episodes, the virus was mainly
      spread to humans through the bite of the mosquito Aedes albopictus. Concomitantly
      to the description of symptoms of an unexpected severity in infants and elderly
      patients, a viral genome microevolution has been highlighted, in particular
      consisting in the acquisition of an A226V mutation in the gene encoding envelope
      glycoprotein E1, which was later found to confer an increased fitness for A.
      albopictus. We previously decrypted the entry pathway used by CHIKV to infect
      human epithelial cells and showed that these mechanisms are modulated by the E1
      A226V mutation. In this report we investigated the conditions for CHIKV entry
      into mosquito cells and we assessed the consequence of E1 gene mutation on these
      parameters. PRINCIPAL FINDINGS: Our main findings indicate that CHIKV infection
      of A. albopictus cell lines is sensitive to Bafilomycin A1 and chloroquine and to
      membrane cholesterol depletion. The E1-226V mutated LR-OPY1 isolate collected
      during the 2005 outbreak in La Reunion replicated more efficiently than the 37997
      African reference strain in C6/36 cells. Moreover, the LR-OPY1 strain displayed
      greater membrane cholesterol dependence and was more sensitive to inhibition of
      endosomal pH acidification. Finally, using electron microscopy, we imaged CHIKV
      entry into C6/36 cells. CONCLUSIONS: Our data support that CHIKV is endocyted
      into A. albopictus cells and requires membrane cholesterol as well as a low-pH
      environment for entry. These features are modulated in some extent by the A226V
      mutation in the E1 gene of the LR-OPY1 isolate. Altogether, our data provide
      information regarding the pathways used by CHIKV to infect A. albopictus cells.

PMID- 22386854
TI  - Generation of reassortant influenza viruses within the non-industrial poultry
      system.
AB  - We compared the genetic and biologic characteristics of 35 influenza viruses of
      different epidemiological backgrounds in Korea, including H3N2 canine influenza
      virus (CIV). Phylogenetic analysis revealed that chicken adapted H9N2 viruses
      (A/chicken/Korea/96006/96 [CK/Kor/96006-like]) have acquired aquatic avian gene
      segments through reassortment, and these reassorted H9N2 viruses were more
      frequently detected from minor poultry species than from industrial poultry.
      Conversely, gene segments from CK/Kor/96006-like viruses were also detected in
      most of the viruses from domestic ducks. Interestingly, domestic ducks, rather
      than wild aquatic birds, harbored close relatives of all eight gene segments of
      H3N2 CIV, which preferred binding to avian receptors. Therefore, bidirectional
      virus transmission events are assumed to have occurred between land-based poultry
      and aquatic poultry, in particular within the non-industrial poultry system.
      These events have contributed to the generation of a novel reassortant, H3N2 CIV.
      To prevent generating other reassortants capable of interspecies transmission,
      gene movements in the non-industrial poultry systems should be clarified and
      managed.

PMID- 22386855
TI  - Management of frontal sinus fractures.
AB  - The traditional treatment of frontal sinus fractures is undergoing a review by
      many clinicians. This review will undoubtedly contribute to the existing
      controversy surrounding the management of patients with this condition. This
      article seeks to further the review and suggest the authors' perspective on a
      more appropriate approach to the care of patients with frontal sinus injuries.

PMID- 22386856
TI  - Surgical anatomy of the nasal cavity and paranasal sinuses.
AB  - The oral cavity and its bony components (maxilla and mandible), along with the
      nose and its related sinuses, constitute most of the face. Because of their
      proximity, disease in one may affect the other, whereas trauma of the midface
      will involve bones common to the oral cavity, nose, and paranasal sinuses. The
      two serve important life-supporting functions, being the portals for nutrition
      and respiration. The paranasal sinuses are pneumatic cavities lined by mucous
      membrane and communicate directly with the nasal cavity. This article presents a
      brief but relevant view of the surgical anatomy of the nasal cavity and paranasal
      sinuses.

PMID- 22386857
TI  - Interactive effects of temperature and copper on photosystem II photochemistry in
      Chlorella vulgaris.
AB  - In natural aquatic ecosystems, temperature conditions may undergo changes
      depending on the depth of the water column or micro-environmental conditions. In
      this study, copper effect on the photosynthetic performance of Chlorella vulgaris
      was investigated at different temperatures by using chlorophyll a fluorescence
      transients and fluorescence imaging parameters. Copper as a pollutant is known to
      be an inhibitor of photosystem II (PSII) photochemistry; therefore it was
      important to know how the change of temperature may alter this effect. PSII
      photochemistry was investigated when C. vulgaris, affected by different copper
      concentrations, was exposed to 24, 28 and 31  degrees C. Increase of temperature
      induced higher alterating effects to PSII quantum yield, primary photosynthetic
      electron transport from water splitting system and consequently higher decrease
      of total photosynthetic performance if compared to copper effect alone.
      Additional temperature effect to copper inhibition increased energy dissipation
      via non-photochemical pathway. In this study we indicated that, when C. vulgaris
      changes temperature conditions, inhibitory effect of copper also undergoes
      changes. For natural aquatic system we may suppose, when algae are distributed at
      different depths of water column, that toxicity effect will be dependent to the
      temperature conditions of the site.

PMID- 22386858
TI  - Modification of the metabolism and toxicity of styrene and styrene oxide in
      hepatic cytochrome P450 reductase deficient mice and CYP2F2 deficient mice.
AB  - Styrene causes toxicity in both the lung and the liver. The study of the
      relationship of this toxicity to the metabolism of styrene has been aided by the
      use of knockout mice for both bioactivation and detoxification pathways. It has
      been hypothesized that CYP2E1 is primarily responsible for styrene bioactivation
      in mouse liver and CYP2F2 in mouse lung. Two knockout strains were used in the
      current studies. Mice deficient in hepatic cytochrome P450 reductase had much
      less hepatic metabolism of styrene to styrene oxide. Styrene (600 mg/kg, i.p.)
      caused significant hepatotoxicity, as determined by serum sorbitol dehydrogenase
      and glutathione levels, in the wild-type but not in the knockout mice. It caused
      lung toxicity, as determined by protein levels, cell number, and lactate
      dehydrogenase activity in the bronchioalveolar lavage fluid of wild-type mice,
      but this effect was less in the knockout mice. In CYP2F2 knockout mice there was
      only a small decrease in the hepatic metabolism of styrene but a very large
      decrease in pulmonary metabolism. As expected the CYP2F2 knockout and wild-type
      mice were equally susceptible to styrene-induced hepatotoxicity, but the knockout
      mice were less susceptible to styrene-induced pneumotoxicity. Although the
      results are inconsistent with the simple hypothesis that styrene pneumotoxicity
      is due to the bioactivation of styrene to styrene oxide by CYYP2F2, they
      demonstrate the importance of both liver and lung in the metabolism of styrene,
      but additional pharmacokinetic studies are needed to help clarify the
      relationship between target organ metabolism and susceptibility.

PMID- 22386859
TI  - Body mass index and screening for colorectal cancer: gender and attitudinal
      factors.
AB  - BACKGROUND: Overweight/obese women and men are at increased risk for colorectal
      cancer (CRC) incidence and mortality. Research examining body mass index (BMI)
      and CRC screening has had mixed results. A clearer understanding of the extent to
      which high-BMI subgroups are screened for CRC is needed to inform planning for
      CRC screening promotions targeting BMI. METHODS: Data were obtained from a
      random, population-based sample of women and men at average-risk for CRC (aged 50
      75 years) during 2004 (n = 1098). Multiple logistic regression analyses were
      conducted to evaluate whether BMI category was significantly associated with the
      probability of reporting recent CRC screening and with the probability of
      agreeing with statements denoting attitudes/perceptions about CRC and screening.
      Attitudes/perceptions about CRC and screening were evaluated as potential
      mediators and moderators of the association between BMI category and CRC
      screening. RESULTS: After controlling for characteristics associated with CRC
      screening, overweight and obese women were each 40% less likely to have CRC
      screening than women with normal-BMI (OR = 0.6, 95% CI:0.4-0.9 and OR = 0.6, 95%
      CI:0.3-0.9). BMI category was unrelated to screening among men. Obese women (but
      not men) were less aware than normal-BMI women that obesity increased risk for
      CRC (OR = 0.5, 95% CI:0.3-0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3
      0.8). However, findings suggest that attitudes/perceptions about CRC and
      screening did not mediate or moderate the association between BMI category and
      CRC screening. CONCLUSION: Overweight/obese women are at increased risk for CRC
      because of their greater BMI and their propensity not to screen for CRC. Study
      findings suggest that potentially modifiable perceptions, e.g., lack of awareness
      of risk for CRC and less worry about CRC, in this subgroup may not explain the
      relationship between BMI category and reduced screening.

PMID- 22386860
TI  - Gender-specific spatio-temporal patterns of colorectal cancer incidence in
      Navarre, Spain (1990-2005).
AB  - INTRODUCTION: In the last ten to twenty years, a stabilization or decline in
      colorectal cancer (CRC) incidence has been observed in some countries across the
      world but not in Spain. Our objective here is to assess the gender-specific CRC
      spatio-temporal pattern in the health areas of Navarre, a Spanish province,
      during the period 1990-2005. METHODS: For each gender, a model with spatio
      temporal CAR (Conditional Autoregressive) distributions is used for smoothing the
      incidence risks. Smoothing is carried out in two dimensions: space and time,
      allowing for a different time evolution in each health area. An estimated
      incidence trend curve for each health area and the corresponding confidence bands
      are obtained. To analyze the evolution of the geographical patterns of CRC
      incidence risks, maps are also provided. RESULTS: In both genders, CRC shows an
      increasing trend in most of the areas. In the second half of the period 1998-2005
      most of the areas have risks above one although not all statistically
      significant. In general females present equal or lower risks than males in all
      areas during the studied period. CONCLUSIONS: Colorectal cancer incidence risk is
      still increasing in the health areas of Navarre. Promoting healthful lifestyles
      for primary prevention and early detection programs could help to reverse the
      trend in the province.

PMID- 22386861
TI  - Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with
      lifestyle factors in a Chinese population.
AB  - BACKGROUND: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have
      been associated with risks of many cancers, little is known about their etiology
      role in gastric cancer (GC) and the potential interacting role with lifestyle
      factors known to damage DNA. METHODS: A population-based study was conducted in 3
      counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of
      GC in China. We investigated the association of polymorphisms IVS12-6T>C and
      IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene-lifestyle
      interaction. RESULTS: The risk of GC was found to be associated with the IVS12-6C
      allele (CC vs TT, OR=2.34, 95% CI: 1.17-4.71) and IVS10+12A allele (GA or AA vs
      GG, OR=1.55, 95% CI: 1.14-2.21; and GA vs GG, OR=1.51, 95% CI: 1.04-2.17).
      Stratified analysis indicated that an increased risk of GC also was observed in:
      suspected familial subjects carrying the IVS12-6T>C (OR=1.68, 95% CI: 1.27-2.66)
      or IVS10+12G>A (OR=2.57, 95% CI: 1.53-4.10); or younger subjects carrying the
      IVS12-6T>C (OR=2.15, 95% CI: 1.24-3.91) or IVS10+12G>A (OR=2.23, 95% CI: 1.20
      4.33); or male subjects carrying the IVS10+12G>A (OR=1.64; 95% CI: 1.10-2.54).
      Furthermore, the combined IVS12-6CC and IVS10+12AA genotypes also significantly
      increased the risk of GC (OR=2.12, 95% CI: 1.22-3.66). Statistically significant
      interactions were observed between: IVS10+12G>A and drinking, high pickled food
      or fried food intake (OR=2.32; 95% CI: 1.43-3.78, OR=2.55; 95% CI: 1.48-4.21 and
      OR=2.88; 95% CI: 1.70-4.94, respectively); and IVS12-6T>C and high pickled food
      intake or fried food intake (OR=2.65; 95% CI: 1.62-4.47 and OR=2.48; 95% CI: 1.42
      4.13, respectively). CONCLUSION: The IVS10+12G>A and IVS12-6T>C polymorphisms in
      MSH2 gene appear to be associated with risk of GC in this Chinese population.
      Risk for GC, stratified by related genotypes, was further modified by drinking,
      high pickled food or fried food intake. Larger prospective studies are needed to
      confirm these findings.

PMID- 22386862
TI  - Preparation of supported lipid membranes for aquaporin Z incorporation.
AB  - There has been a recent surge of interest to mimic the performance of natural
      cellular membranes by incorporating water channel proteins-aquaporins (AQPs) into
      various ultrathin films for water filtration applications. To make biomimetic
      membranes one of the most crucial steps is preparing a defect-free platform for
      AQPs incorporation on a suitable substrate. In this study two methods were used
      to prepare supported lipid membranes on NF membrane surfaces under a benign pH
      condition of 7.8. One method was direct vesicle fusion on a hydrophilic membrane
      NF-270; the other was vesicle fusion facilitated by hydraulic pressure on a
      modified hydrophilic NF-270 membrane whose surface has been spin-coated with
      positively charged lipids. Experiments revealed that the supported lipid membrane
      without AQPs prepared by the spin coating plus vesicle fusion had a much lower
      defect density than that prepared by vesicle fusion alone. It appears that the
      surface roughness and charge are the main factors determining the quality of the
      supported lipid membrane. Aquaporin Z (AqpZ) proteins were successfully
      incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes and
      its permeability was measured by the stopped-flow experimental procedure.
      However, after the proteoliposomes have been fused onto the modified substrate,
      the AqpZ function in the resultant membrane was not observed and AFM images
      showed distinct aggregations of unfused proteoliposomes or AqpZ proteins on the
      substrate surface. It is speculated that the inhibition of AqpZ function may be
      caused by the low lipid mobility on the NF membrane surface. Further
      investigations to evaluate and optimize the structure-performance relationship
      are required.

PMID- 22386863
TI  - Effects of gelucire content on stability, macrophage interaction and blood
      circulation of nanoparticles engineered from nanoemulsions.
AB  - The main objective of the study is to investigate the efficacy of Gelucire 44/14
      (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle
      (NP) and to assess the effects on key NP properties and functions. NPs from oil
      in-water nanoemulsion precursors were prepared using binary mixtures of CA and
      gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes
      of gelucire-based NPs (128-183 nm) were five times lower than control NPs (made
      without gelucire). All the NPs (with or without gelucire component) did not
      activate macrophages as monitored by reactive oxygen species production. Results
      from differential scanning calorimetry, FT-IR and multimodal light scattering
      measurements demonstrated the involvement of gelucire component in achieving
      homogeneous CA/gelucire particle populations that were stable on storage. The P
      glycoprotein (P-gp) function assay in MES-Dx5 cells showed the potential of
      gelucire-based NPs in inhibiting rhodamine 123 efflux. Similarly, the extent of
      NP uptake by macrophage (RAW 264.7 cell) was dependent on the amount of gelucire
      component (inverse relationship; R(2)=0.996). NPs made with CA/gelucire mixture
      (at 50%, w/w gelucire) were the most effective in blood circulation studies in
      BALB/c mice. Additional studies with paclitaxel-loaded NPs demonstrated that the
      retention of gelucire-based NPs in blood circulation was comparable to NPs coated
      with DSPE-PEG(2000) (p>0.6). The over-all work indicated the potential efficacy
      of gelucire as a safe and biocompatible excipient that can serve multiple
      functions in enhancing the performance of lipid-based NP drug delivery systems.

PMID- 22386864
TI  - Epigenetic patterns in systemic sclerosis and their contribution to attenuated
      CD70 signaling cascades.

PMID- 22386865
TI  - Sublingual administration of Lactobacillus paracasei KW3110 inhibits Th2
      dependent allergic responses via upregulation of PD-L2 on dendritic cells.
AB  - Lactic acid bacteria have potential in immunomodulation therapy, but their
      clinical efficacy and underlying mechanisms are unclear. We aimed to clarify the
      anti-allergic immune responses induced by intragastric and sublingual
      administration of heat-killed Lactobacillus paracasei KW3110 and Lactobacillus
      acidophilus L-92. The KW3110 strain (but not the L-92 strain) enhanced ovalbumin
      (OVA)-induced expression of CCR-7 and PD-L2 in murine dendritic cells (DCs), and
      strongly inhibited IL-5 and IL-13 production in vitro in co-cultures with Th2
      skewed CD4(+) T cells from DO11.10 transgenic mice. Sublingual administration of
      low-dose KW3110 (but not L-92) to OVA-sensitized mice selectively suppressed
      serum IgE production and Th2 cytokine expression in cervical lymph nodes, and
      significantly improved symptoms after OVA provocation in vivo. KW3110 probably
      accelerates DC migration into the regional lymph nodes and inhibits Th2 cytokine
      production through enhanced CCR-7 and PD-L2 expression. Thus, sublingual KW3110
      administration may be effective in reducing allergic inflammation.

PMID- 22386867
TI  - GC-MS and GC-IRD analysis of 2-, 3- and 4-methylmethamphetamine and 2-, 3- and 4
      methylamphetamine.
AB  - 4-Methylmethamphetamine has been detected in samples submitted for analysis in
      several states throughout Australia. Six ring substituted methyl isomers of
      methamphetamine and amphetamine were synthesised and analysed. As the
      regioisomeric 2-, 3- and 4-methylmethamphetamine and 2-, 3- and 4
      methylamphetamine have virtually identical mass spectra, the use of MS is an
      ineffective technique to discriminate between these closely related compounds. We
      set out to determine whether the regioisomers could be differentiated by a
      combination of GC-MS, acetyl derivatisation and GC-IRD. We demonstrate that the
      three isomers of methylmethamphetamine and methylamphetamine can be separated by
      GC, and a combination of acetyl derivatisation and vapour phase IR can identify
      the specific ring substituted compound.

PMID- 22386866
TI  - Different signaling mechanisms regulating IL-6 expression by LPS between gingival
      fibroblasts and mononuclear cells: seeking the common target.
AB  - To reduce connective tissue IL-6 level stimulated by LPS, it is essential to
      control IL-6 expression in both mononuclear cells and fibroblasts. However, it is
      unclear whether the regulatory mechanisms for both cells are similar or not. In
      this study, we found that signaling pathways mediating LPS-stimulated IL-6 in
      mononuclear U937 cells and fibroblasts were different. Furthermore, our studies
      showed that while LPS activated AP-1 and NFkappaB in U937 cells, it only
      activated NFkappaB in fibroblasts. Analysis of nuclear AP-1 subunits showed that
      LPS stimulated c-Fos, Fra-1 and Jun D activities in U937 cells, but not
      fibroblasts. The lack of ERK involvement in LPS-stimulated IL-6 in fibroblasts
      was further supported by the observations that simvastatin, which is known to
      target ERK-AP-1, failed to inhibit LPS-stimulated IL-6 by fibroblasts. Finally,
      we showed that targeting NFkappaB pathway was highly effective in inhibition of
      LPS-stimulated IL-6 in coculture of U937 cells and fibroblasts.

PMID- 22386868
TI  - Enzymology of tRNA modification in the bacterial MnmEG pathway.
AB  - Among all RNAs, tRNA exhibits the largest number and the widest variety of post
      transcriptional modifications. Modifications within the anticodon stem loop,
      mainly at the wobble position and purine-37, collectively contribute to stabilize
      the codon-anticodon pairing, maintain the translational reading frame, facilitate
      the engagement of the ribosomal decoding site and enable translocation of tRNA
      from the A-site to the P-site of the ribosome. Modifications at the wobble
      uridine (U34) of tRNAs reading two degenerate codons ending in purine are complex
      and result from the activity of two multi-enzyme pathways, the IscS-MnmA and
      MnmEG pathways, which independently work on positions 2 and 5 of the U34
      pyrimidine ring, respectively, and from a third pathway, controlled by TrmL
      (YibK), that modifies the 2'-hydroxyl group of the ribose. MnmEG is the only
      common pathway to all the mentioned tRNAs, and involves the GTP- and FAD
      dependent activity of the MnmEG complex and, in some cases, the activity of the
      bifunctional enzyme MnmC. The Escherichia coli MnmEG complex catalyzes the
      incorporation of an aminomethyl group into the C5 atom of U34 using methylene
      tetrahydrofolate and glycine or ammonium as donors. The reaction requires GTP
      hydrolysis, probably to assemble the active site of the enzyme or to carry out
      substrate recognition. Inactivation of the evolutionarily conserved MnmEG pathway
      produces a pleiotropic phenotype in bacteria and mitochondrial dysfunction in
      human cell lines. While the IscS-MnmA pathway and the MnmA-mediated
      thiouridylation reaction are relatively well understood, we have limited
      information on the reactions mediated by the MnmEG, MnmC and TrmL enzymes and on
      the precise role of proteins MnmE and MnmG in the MnmEG complex activity. This
      review summarizes the present state of knowledge on these pathways and what we
      still need to know, with special emphasis on the MnmEG pathway.

PMID- 22386869
TI  - Interaction of Listeria monocytogenes autolysin amidase with glycosaminoglycans
      promotes listerial adhesion to mouse hepatocytes.
AB  - Adherence to the cell surface is a key event during infection of pathogenic
      microorganisms. We have previously reported that autolysin amidase (Ami) of
      Listeria monocytogenes promotes an efficient listerial adherence to mouse
      hepatocytes and requires for listerial pathogenicity. Cell wall anchoring (CWA)
      domain of Ami has been shown to bind lipoteichoic acid on listerial cell wall but
      the binding of Ami to host cell surface molecules remains to be determined. In
      this study, we present evidence here that Ami promotes efficient adherence of L.
      monocytogenes to mouse hepatocytes mediated by glycosaminoglycans (GAGs). The
      adhesion of L. monocytogenes wild type but not Ami-deficient mutant to the
      hepatocytes was dramatically attenuated by 4-nitrophenyl-beta-D-xylopyranoside, a
      specific inhibitor of GAG association to cell surface. Full-length and truncated
      Ami were used to investigate the binding of Ami to GAGs and we found that four
      repeated CWA of Ami is sufficient to bind GAGs on the host cell surface.
      Competitive assay and surface plasmon resonance demonstrated that Ami interacts
      with sulfated GAGs but not non-sulfated GAGs. The results suggest that Ami acts
      as an adhesin of L. monocytogenes to hepatocytes by interaction via its four
      repeated CWA domain and sulfated GAGs.

PMID- 22386870
TI  - Bafibrinase: A non-toxic, non-hemorrhagic, direct-acting fibrinolytic serine
      protease from Bacillus sp. strain AS-S20-I exhibits in vivo anticoagulant
      activity and thrombolytic potency.
AB  - A non-toxic, direct-acting fibrinolytic serine protease (Bafibrinase)
      demonstrating thrombolytic and anticoagulant properties was purified from
      Bacillus sp. strain AS-S20-I. Bafibrinase was monomeric, with a molecular mass of
      32.3 kDa. The peptide mass fingerprinting of Bafibrinase revealed only 8.3%
      sequence coverage, suggesting it was a novel fibrinolytic enzyme. However, two of
      the tryptic digested de novo peptide sequences of Bafibrinase demonstrated good
      similarity with endopeptidases possessing serine in their catalytic triad.
      Further, catalytic activity of Bafibrinase was inhibited by serine protease
      inhibitor reinforcing this is a subtilisin-like serine protease. The apparent
      K(m) and V(max) values of Bafibrinase towards fibrin were determined as 0.24 MUM
      and 2.8 MUmol/min, respectively. It showed a K(m) value of 0.139 mM towards a
      chromogenic substrate for plasmin (D-Val-Leu-Lys-p-Nitroanilide dihydrochloride)
      and optimum activity at physiological conditions (37  degrees C and pH 7.4).
      Based on the cleavage pattern of fibrin and fibrinogen, Bafibrinase may be
      classified as an alpha,beta-fibrinogenase. Bafibrinase could not degrade collagen
      and was non-cytotoxic to HT29 cells or mammalian erythrocytes. Further,
      Bafibrinase at a dose of 2 mg/kg was devoid of toxicity as well as hemorrhagic
      activity on BALB/c mouse model, supporting its suitability for the development of
      a better and safer thrombolytic drug. Bafibrinase was also superior to human
      plasmin in degrading in vitro thrombus. The in vivo anticoagulant nature of
      Bafibrinase is being explored for the treatment and prevention of thrombosis and
      other cardiovascular diseases.

PMID- 22386871
TI  - Novel protein-protein interactions between Entamoeba histolyticad
      phosphoglycerate dehydrogenase and phosphoserine aminotransferase.
AB  - Physical interactions between d-phosphoglycerate dehydrogenase (EhPGDH) and
      phosphoserine aminotransferase (EhPSAT) from an enteric human parasite Entamoeba
      histolytica was observed by pull-down assay, gel filtration chromatography,
      chemical cross-linking, emission anisotropy, molecular docking and molecular
      dynamic simulations. The protein-protein complex had a 1:1 stochiometry with a
      dissociation constant of 3.453 * 10(-7) M. Ionic interactions play a significant
      role in complex formation and stability. Analysis of the energy minimized average
      simulated model of the protein complex show that the nucleotide binding domain of
      EhPGDH specifically interacts with EhPSAT. Denaturation studies suggest that the
      nucleotide binding domain (Nbd) and substrate binding domain (Sbd) of EhPGDH are
      independent folding/unfolding units. Thus the Nbd-EhPGDH was separately cloned
      over-expressed and purified to homogeneity. Fluorescence anisotropy study show
      that the purified Nbd interacts with EhPSAT. Forward enzyme catalyzed reaction
      for the EhPGDH-PSAT complex showed efficient Km values for 3-phosphoglyceric acid
      as compared to only EhPGDH suggesting a possibility of substrate channelling in
      the protein complex.

PMID- 22386872
TI  - Involvement of transient receptor potential vanilloid type 1 channels in the pro
      convulsant effect of anandamide in pentylenetetrazole-induced seizures.
AB  - Anandamide, an endogenous agonist of CB(1) receptors, also activates TRPV1 but at
      a higher concentration. Studies demonstrate the anticonvulsant activity of
      anandamide via CB(1) receptors, while its action through TRPV1 is still
      ambiguous. Thus, the present study investigated the influence of anandamide on
      pentylenetetrazole-induced seizures in mice pretreated with TRPV1 or CB(1)
      receptor antagonists. Acute intracerebroventricular administration of low doses
      of anandamide (10, 20, or 40MUg/mouse) produced anticonvulsant effect, while the
      pro-convulsant effect was evident at high doses (80 or 100MUg/mouse).
      Interestingly, AM251 (2MUg/mouse), a CB(1) antagonist pretreatment blocked the
      anticonvulsant effect, but augmented the pro-convulsant effect. Conversely, in
      the presence of inactive dose of capsazepine (1MUg/mouse), a TRPV1 antagonist,
      anandamide exhibited significant anticonvulsant effect even at high doses with no
      change in its anticonvulsant effect. Moreover, mice treated with capsaicin, a
      TRPV1 agonist (10, or 100MUg/mouse) exhibited pro-convulsant activity that was
      blocked by capsazepine pretreatment. However, capsazepine, per se at doses 10 or
      100MUg/mouse exhibited anticonvulsant effect. Like anandamide, the agents (AM404
      and URB597), which increase its synaptic concentrations produced similar biphasic
      effects. Thus, these results indicate that anandamide exhibits both pro- and
      anticonvulsant activities by activating TRPV1 and CB(1) receptor respectively.

PMID- 22386873
TI  - Clinical characteristics, etiology and long-term outcome of epilepsia partialis
      continua in adult patients in Thailand.
AB  - OBJECTIVE: Epilepsia partialis continua (EPC) is clinically defined as a syndrome
      of continuous focal jerking of a body part. EPC has various etiologies and
      outcomes depending on its cause. Most studies on EPC have been conducted in
      Western countries and no study on the long-term outcome in adult onset epilepsia
      partialis continua has been reported. The aim of this study was to analyze the
      clinical characteristics, etiology, and treatment outcome and measurement to
      identify conditions that are predictive of long-term excellent outcome following
      epilepsia partialis continua in Thailand. METHODS: Our study was characterized by
      a retrospective systematic data collection between 2003 and 2010 that lead to the
      inclusion of a total of 75 patients, with epilepsia partialis continua at
      Songklanagarind Hospital, Thailand. All of the patients received brain CT scans
      or MRIs after diagnosis with EPC. Basic laboratory investigations including blood
      sugar, blood urea nitrogen, creatinine, electrolyte, calcium, liver function, and
      complete blood count tests were performed. Additionally, routine
      electroencephalography were performed and antiepileptic drugs were given to all
      patients. Therapeutic outcomes and the degree of seizure control after discharge
      were determined by the functional status and Seizure Frequency Scoring Systems,
      respectively. KEY FINDING: All of our patients manifested as motor EPC. The mean
      duration of EPC was 6.2 days (range 1-30 days) and the most frequent distribution
      of EPC involved the face and arms (42.7%). Hyperglycemia was the most common
      cause of EPC (34 patients, 45.3%). Fifty-one patients had an excellent outcome
      and 24 patients had a non-excellent outcome. All of the patients with
      hyperglycemia had an excellent outcome and required no antiepileptics in the long
      term. Predictors of excellent outcome in the scoring system for seizure frequency
      were metabolic or hyperglycemia-induced EPC, monotherapy and duration of EPC.
      SIGNIFICANCE: The characteristics of epilepsia partialis continua in this study
      were different from those of EPC in Western countries. Its most common cause was
      hyperglycemia and prognostic factors depended on etiology, number of AEDs, and
      duration of EPC.

PMID- 22386874
TI  - [Descriptive study on the improvement of quality perceived after the introduction
      of a clinical pathway by patients subjected to bariatric surgery].
AB  - OBJECTIVES: To evaluate the level of perceived satisfaction in patients
      undergoing bariatric procedures after implementing a clinical pathway, and to
      analyse factors related to a high degree of satisfaction. MATERIAL AND METHODS: A
      cohort of patients was invited to fulfil, anonymously and voluntarily, a SERVQHOS
      survey the day before hospital discharge. RESULTS: Seventy-one (53 female) out of
      103 patients (70%) responded to the questionnaire. A total of 97.3% of patients
      who completed the survey answered to the questions "as expected" or "above
      expectations". Most (98.6%) of the patients were "very satisfied" or "satisfied"
      with the care received, and 97.2% would recommend the hospital to others.
      Questions better related to overall satisfaction were technology used (P=.008),
      staff appearance (P=.019), the interest of staff to fulfil a promise (P=.002),
      and to solve the problems of the patient (P=.021), information provided by the
      medical staff (P=.039) and waiting time until being seen by the doctor (P=.002).
      In the multivariate study, only the "personalized care" achieved the category of
      a predictive variable (r=0.52). Median hospital stay was 3 days, and 76% of
      patients considered it adequate. The percentage of highest satisfaction was
      significantly lower in female, singles, unemployed, and those with academic
      studies. CONCLUSIONS: Morbid obese patients included in a clinical pathway of
      bariatric surgery had a good perception with the care received.

PMID- 22386875
TI  - [Measuring patient satisfaction and identifying opportunities for improvement in
      the preparation of bariatric surgery patients].
AB  - OBJECTIVE: To evaluate the satisfaction of patients candidates for bariatric
      surgery with the performance of a group training program prior to surgery,
      identifying opportunities for improvement in the program and evaluating
      participants satisfaction following their implementation. METHOD: An "ad hoc"
      designed survey was used, addressed to assess opinions on different aspects of
      the program, overall satisfaction and identification of areas for improvement.
      The survey was administered to two groups of patients: the first after one year
      of implementation of the program to identify suggestions for improvement, and the
      second after one year of the implementation of the improvement. A total of 112
      patients were assessed, 66 in the first pass of the questionnaire and 46 in the
      second. Both groups were homogeneous in demographic variables RESULTS: The main
      improvement detected was expert patients in the preparation of the program. After
      implantation, slight changes in the ratings of the questions were produced, that
      were not significant. Overall satisfaction rose from 9.5 to 9.74 out of 10. The
      other proposals for improvement were to improve audiovisuals and to fit the room
      furniture to the characteristics of the patients. CONCLUSIONS: The very high
      satisfaction levels obtained are usual in studies on hospital satisfaction, our
      results still being above the studies consulted, as well as in levels of
      excellence. This prevents statistically significant differences being found.
      There were no significant differences in the results before and after
      implementation of improvement. Continuous assessment allows new possibilities for
      improvement.

PMID- 22386876
TI  - [Adherence, the Achilles heel of cardiovascular disease].

PMID- 22386878
TI  - Effect of Tie-2 conditional deletion of BDNF on atherosclerosis in the ApoE null
      mutant mouse.
AB  - The reduced expression (haplodeficiency) of the main brain derived neurotrophic
      factor receptor, namely TrkB is associated with reduced atherosclerosis, smooth
      muscle cells accumulation and collagen content in the lesion. These data support
      the concept that brain derived neurotrophic factor of vascular origin may
      contribute to atherosclerosis. However, to date, no experimental approach was
      possible to investigate this issue due to the lethality of brain derived
      neurotrophic factor null mice. To overcome these limitations, we generated a
      mouse model with a conditional deletion of brain derived neurotrophic factor in
      endothelial cells (Tie-2 Cre recombinase) on an atherosclerotic prone background
      (apolipoprotein E knock out) and investigated the effect of conditional brain
      derived neurotrophic factor deficiency on atherosclerosis. Despite brain derived
      neurotrophic factor reduction in the vascular wall, mice with conditional
      deletion of brain derived neurotrophic factor did not develop larger
      atherosclerotic lesion compared to controls. Smooth muscle cell content as well
      as the distribution of total and fibrillar collagen was similar in the
      atherosclerotic lesions from mice with brain derived neurotrophic factor
      conditional deficiency compared to controls. Finally an extended gene expression
      analysis failed to identify pro-atherogenic gene expression patterns among the
      animal with brain derived neurotrophic factor deficiency. In spite of the reduced
      brain derived neurotrophic factor expression, similar atherosclerosis development
      was observed in the brain derived neurotrophic factor conditional deficient mouse
      compared to controls. These pieces of evidence indicate that endothelial derived
      brain derived neurotrophic factor is not a pro-atherogenic factor and would
      rather suggest to investigate the role of other TrkB activators on
      atherosclerosis.

PMID- 22386877
TI  - Loss of c-Met accelerates development of liver fibrosis in response to CCl(4)
      exposure through deregulation of multiple molecular pathways.
AB  - HGF/c-Met signaling plays a pivotal role in hepatocyte survival and tissue
      remodeling during liver regeneration. HGF treatment accelerates resolution of
      fibrosis in experimental animal models. Here, we utilized Met(fl/fl);Alb-Cre(+/-)
      conditional knockout mice and a carbon tetrachloride(CCl(4))-induced liver
      fibrosis model to formally address the role of c-Met signaling in hepatocytes in
      the context of chronic tissue injury. Histological changes during injury (4weeks)
      and healing phase (4weeks) were monitored by immunohistochemistry; expression
      levels of selected key fibrotic molecules were evaluated by western blotting, and
      time-dependent global transcriptomic changes were examined using a microarray
      platform. Loss of hepatocyte c-Met signaling altered hepatic microenvironment and
      aggravated hepatic fibrogenesis. Greater liver damage was associated with
      decreased hepatocyte proliferation, excessive stellate cell activation and rapid
      dystrophic calcification of necrotic areas. Global transcriptome analysis
      revealed a broad impact of c-Met on critical signaling pathways associated with
      fibrosis. Loss of hepatocyte c-Met caused a strong deregulation of chemotactic
      and inflammatory signaling (MCP-1, RANTES, Cxcl10) in addition to modulation of
      genes involved in reorganization of the cytoskeletal network (Actb, Tuba1a,
      Tuba8), intercellular communications and adhesion (Adam8, Icam1, Itgb2), control
      of cell proliferation (Ccng2, Csnk2a, Cdc6, cdk10), DNA damage and stress
      response (Rad9, Rad52, Ercc4, Gsta1 and 2, Jun). Our study demonstrates that
      deletion of c-Met receptor in hepatocytes results in pronounced changes in
      hepatic metabolism and microenvironment, and establishes an essential role for c
      Met in maintaining the structural integrity and adaptive plasticity of the liver
      under adverse conditions.

PMID- 22386879
TI  - How does phasic alerting improve performance in patients with unilateral neglect?
      A systematic analysis of attentional processing capacity and spatial weighting
      mechanisms.
AB  - In visual hemi-neglect, non-spatial deficits such as reduced intrinsic alertness
      can significantly modulate the degree of left visual field inattention. However,
      to date, the precise mechanisms mediating this effect are hardly understood. In
      the present study, we assessed the influence of increased alertness on both
      general attentional capacity (perceptual processing speed) and spatial
      attentional selection processes (spatial distribution of attentional weighting).
      For this purpose, a whole-report paradigm based on Bundesen's 'theory of visual
      attention' (TVA) was combined with a non-spatial, visual alerting cue. Three
      different cue-target stimulus onset asynchronies (SOAs; of 80, 200, and 650 ms),
      allowed us to observe the time course of the alerting-cue effects. A group of six
      patients with visual hemi-neglect was examined and their performance compared
      with six healthy control subjects matched for age, gender, and education. In
      neglect patients, the alerting cue evoked a phasic increase of perceptual
      processing speed. However, this effect was mainly found in the ipsilateral, i.e.
      in the "preserved" hemifield. Importantly, however, patients displayed a fast
      evolving and short-lasting, phasic modulation of spatial attentional weighting,
      with a re-distribution of attentional weights from the pathological rightward
      bias to a normal, more balanced distribution of visual attention. In control
      participants, the cueing effects on perceptual processing speed and spatial
      weighting were generally less pronounced than in neglect patients. Replicating
      results of a prior study, cueing induced a stable, slightly leftward,
      distribution of attentional weights, whilst in the no-cue condition, a temporary
      rightward shift of attentional weights was found. This pattern of effects
      suggests a close interaction between alertness and spatial-attentional weighting
      in the syndrome of visual hemi-neglect. It supports the hypothesis that the
      manifestation of spatial neglect involves at least in part intrinsic alertness
      deficits. It also provides clues to a more detailed account of the mechanisms
      responsible for alleviating neglect in patients following manipulations of the
      alertness level, both in the short (cueing) and in the long term (alertness
      training).

PMID- 22386880
TI  - Attentional control: temporal relationships within the fronto-parietal network.
AB  - Selective attention to particular aspects of incoming sensory information is
      enabled by a network of neural areas that includes frontal cortex, posterior
      parietal cortex, and, in the visual domain, visual sensory regions. Although
      progress has been made in understanding the relative contribution of these
      different regions to the process of visual attentional selection, primarily
      through studies using neuroimaging, rather little is known about the temporal
      relationships between these disparate regions. To examine this, participants
      viewed two rapid serial visual presentation (RSVP) streams of letters positioned
      to the left and right of fixation point. Before each run, attention was directed
      to either the left or the right stream. Occasionally, a digit appeared within the
      attended stream indicating whether attention was to be maintained within the same
      stream ('hold' condition) or to be shifted to the previously ignored stream
      ('shift' condition). By titrating the temporal parameters of the time taken to
      shift attention for each participant using a fine-grained psychophysics paradigm,
      we measured event-related potentials time-locked to the initiation of spatial
      shifts of attention. The results revealed that shifts of attention were evident
      earlier in the response recorded over frontal than over parietal electrodes and,
      importantly, that the early activity over frontal electrodes was associated with
      a successful shift of attention. We conclude that frontal areas are engaged early
      for the purpose of executing an attentional shift, likely triggering a cascade
      through the fronto-parietal network ultimately, resulting in the attentional
      modulation of sensory events in posterior cortices.

PMID- 22386881
TI  - Fatty acids revert the inhibition of respiration caused by the antidiabetic drug
      metformin to facilitate their mitochondrial beta-oxidation.
AB  - While metformin has been widely used to treat type 2 diabetes for the last fifty
      years, its mode of action remains unclear. Hence, we investigated the short-term
      alterations in energy metabolism caused by metformin administration in 3T3-L1
      adipocytes. We found that metformin inhibited mitochondrial respiration, although
      ATP levels remained constant as the decrease in mitochondrial production was
      compensated by an increase in glycolysis. While AMP/ATP ratios were unaffected by
      metformin, phosphorylation of AMPK and its downstream target acetyl-CoA
      carboxylase augmented. The inhibition of respiration provoked a rapid and
      sustained increase in superoxide levels, despite the increase in UCP2 and
      superoxide dismutase activity. The inhibition of respiration was rapidly reversed
      by fatty acids and thus respiration was lower in treated cells in the presence of
      pyruvate and glucose while rates were identical to control cells when palmitate
      was the substrate. We conclude that metformin reversibly inhibits mitochondrial
      respiration, it rapidly activates AMPK without altering the energy charge, and it
      inhibits fatty acid synthesis. Mitochondrial beta-oxidation is facilitated by
      reversing the inhibition of complex I and, presumably, by releasing the
      inhibition of carnitine palmitoyltransferase. This article is part of a Special
      Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22386882
TI  - The coupling mechanism of respiratory complex I - a structural and evolutionary
      perspective.
AB  - Complex I is a key enzyme of the respiratory chain in many organisms. This multi
      protein complex with an intricate evolutionary history originated from the
      unification of prebuilt modules of hydrogenases and transporters. Using recently
      determined crystallographic structures of complex I we reanalyzed evolutionarily
      related complexes that couple oxidoreduction to trans-membrane ion translocation.
      Our analysis points to the previously unnoticed structural homology of the
      electron input module of formate dehydrogenlyases and subunit NuoG of complex I.
      We also show that all related to complex I hydrogenases likely operate via a
      conformation driven mechanism with structural changes generated in the conserved
      coupling site located at the interface of subunits NuoB/D/H. The coupling
      apparently originated once in evolutionary history, together with subunit NuoH
      joining hydrogenase and transport modules. Analysis of quinone oxidoreduction
      properties and the structure of complex I allows us to suggest a fully reversible
      coupling mechanism. Our model predicts that: 1) proton access to the ketone
      groups of the bound quinone is rigorously controlled by the protein, 2) the
      negative electric charge of the anionic ubiquinol head group is a major driving
      force for conformational changes. This article is part of a Special Issue
      entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22386885
TI  - Effect of shock and mixed loading on the performance of SND based sequencing
      batch reactors (SBR) degrading nitrophenols.
AB  - The effect of nitrophenolic shock loads on the performance of three lab scale
      SBRs was studied using a synthetic feed. Nitrophenols were biotransformed by
      Simultaneous heterotrophic Nitrification and aerobic Denitrification (SND) using
      a specially designed single sludge biomass containing Thiosphaera pantotropha.
      Reactors R1, R2 and R3 were fed with 200mg/L concentration of 4-nitrophenol (4
      NP), 2,4-dinitrophenol (2,4-DNP), and 2,4,6-trinitrophenol (2,4,6-TNP) whereas
      reactor R was used as a background control. Three nitrophenolic shock loadings of
      400, 600 and 800 mg/Ld were administrated by increasing the influent
      nitrophenolic concentration while keeping the hydraulic retention time as 48 h.
      The shocks were given continuously for a period of 4 days before switching back
      to normal nitrophenolic loading (200mg/Ld). The reactors were allowed to recover
      to normal performance level before administrating the next nitrophenolic shock
      load. The study showed that a nitrophenolic shock load, as high as 600 mg/Ld was
      completely degraded by the 4-NP & 2,4-DNP bioreactors while almost half degraded
      by the 2,4,6-TNP bioreactor without affecting the reactor's performance
      irreversibly. After resuming the normal nitrophenolic loading, it took almost 8
      10 days for the reactors to recover from the shock effect. The study was further
      extended to evaluate the maximum possible mixed nitrophenolic loading (4-NP:2,4
      DNP:2,4,6-TNP 1:1:1) to which a reactor (R3) containing 2,4,6-TNP acclimated
      single sludge biomass can be exposed without hampering the reactor performance
      irreversibly. The reactor was able to achieve pseudo-steady-state at a mixed
      nitrophenolic loading of 300 mg/Ld with more than 90% removal of all the three
      nitrophenols, but could remove half of the mixed nitrophenolic loading of 600
      mg/Ld.

PMID- 22386884
TI  - Developing environment-specific water quality guidelines for suspended
      particulate matter.
AB  - It is generally well recognised that suspended particulate matter (SPM), from
      nano-scale particles to sand-sized sediments, can cause serious degradation of
      aquatic ecosystems. However, at present there is a poor understanding of the SPM
      conditions that water quality managers should aim to achieve in contrasting
      environments in order to support good ecological status. In this article, we
      analyse long-term SPM data collected from a wide range of reference-condition
      temperate environments in the UK (638 stream/river sites comprising 42 different
      ecosystem-types). One-way analysis of variance reveals that there is a
      statistically significant difference (p < 0.001) between the background SPM
      concentrations observed in contrasting ecosystems that are in reference condition
      (minimal anthropogenic disturbance). One of the 42 ecosystems studied had mean
      background concentrations of SPM in excess of the current European Union (EU)
      water quality guideline, despite being in reference condition. The implications
      of this finding are that the EU's current blanket water quality guideline (25 mg
      L(-1) for all environments) is inappropriate for this specific ecosystem-type
      which will be non-compliant with the guideline regardless of the intensity of
      land-use. The other 41 ecosystems studied had mean concentrations below the
      current EU water quality guideline. However, this does not necessarily mean that
      the guideline is appropriate for these ecosystems, as previous research has
      demonstrated that detrimental impacts can be experienced by some freshwater
      organisms, of all trophic levels, when exposed to concentrations below 25 mg L(
      1). Therefore, it is suggested here that it is likely that some ecosystems,
      particularly those with mean concentrations in the 0.00-5.99 mg L(-1) range,
      require much lower guideline values in order to be effectively protected. We
      propose a model for predicting environment-specific water quality guidelines for
      SPM. In order to develop this model, the 638 reference condition sites were first
      classified into one of five mean background SPM ranges (0.00-5.99, 6.00-11.99,
      12.00-17.99, 18.00-23.99 and >24.00 mg L(-1)). Stepwise Multiple Discriminant
      Analysis (MDA) of these ranges showed that a site's SPM range can be predicted as
      a function of: mean annual air temperature, mean annual precipitation, mean
      altitude of upstream catchment, distance from source, slope to source, channel
      width and depth, the percentage of catchment area comprised of clay, chalk, and
      hard rock solid geology, and the percentage of the catchment area comprised of
      blown sand as the surface (drift) material. The MDA technique, with cross
      validation (Wilks-Lambda 0.358, p 0.000), can predict the correct or the next
      closest SPM range of a site in 90% of cases. This technique can also predict SPM
      range membership in a probabilistic manner, allowing for an estimate of
      uncertainty to be made in the allocation of a site to an environment-specific SPM
      range.

PMID- 22386886
TI  - Fate and transport of elemental copper (Cu0) nanoparticles through saturated
      porous media in the presence of organic materials.
AB  - Column experiments were performed to assess the fate and transport of nanoscale
      elemental copper (Cu(0)) particles in saturated quartz sands. Both effluent
      concentrations and retention profiles were measured over a broad range of
      physicochemical conditions, which included pH, ionic strength, the presence of
      natural organic matter (humic and fulvic acids) and an organic buffer (Trizma).
      At neutral pHs, Cu(0) nanoparticles were positively charged and essentially
      immobile in porous media. The presence of natural organic matter, trizma buffer,
      and high pH decreased the attachment efficiency facilitating elemental copper
      transport through sand columns. Experimental results suggested the presence of
      both favourable and unfavourable nanoparticle interactions causes significant
      deviation from classical colloid filtration theory.

PMID- 22386887
TI  - Relating reverse and forward solute diffusion to membrane fouling in osmotically
      driven membrane processes.
AB  - Osmotically driven membrane processes, such as forward osmosis (FO) and pressure
      retarded osmosis (PRO), are attracting increasing interest in research and
      applications in environment and energy related fields. In this study, we
      systematically investigated the alginate fouling on an osmotic membrane during FO
      operation using four types of draw solutions (NaCl, MgCl(2), CaCl(2) and
      Ca(NO(3))(2)) to elucidate the relationships between reverse (from draw solution
      to feed solution) and forward (from feed solution to draw solution) solute
      diffusion, and membrane fouling. At the same water flux level (achieved by
      adjusting the draw solution concentration), the greatest reverse solute diffusion
      rate was observed for NaCl draw solution, followed by Ca(NO(3))(2) draw solution,
      and then CaCl(2) draw solution and MgCl(2) draw solution, the order of which was
      consistent with that of their solute permeability coefficients. Moreover, the
      reverse solute diffusion of draw solute (especially divalent cation) can change
      the feed solution chemistry and thus enhance membrane fouling by alginate, the
      extent of which is related to the rate of the reverse draw solute diffusion and
      its ability to interact with the foulant. The extent of fouling for the four
      types of draw solution followed an order of Ca(NO(3))(2) > CaCl(2) >> MgCl(2) >
      NaCl. On the other hand, the rate of forward diffusion of feed solute (e.g.,
      Na(+)) was in turn promoted under severe membrane fouling in active layer facing
      draw solution orientation, which may be attributed to the fouling enhanced
      concentration polarization (pore clogging enhanced ICP and cake enhanced
      concentration polarization). The enhanced concentration polarization can lead to
      additional water flux reduction and is an important mechanism governing the water
      flux behavior during FO membrane fouling. Findings have significant implications
      for the draw solution selection and membrane fouling control in osmotically
      driven membrane processes.

PMID- 22386888
TI  - Establishing physico-chemical reference conditions in Mediterranean streams
      according to the European Water Framework Directive.
AB  - Type-specific physico-chemical reference conditions are required for the
      assessment of ecological status in the Water Framework Directive context,
      similarly to the biological and hydro-morphological elements. This directive
      emphasises that natural variability of quality elements in high status (reference
      condition) needs to be quantified. Mediterranean streams often present a marked
      seasonal pattern in hydrological, biological and geochemical processes which
      could affect physico-chemical reference conditions. This study establishes
      general physico-chemical reference conditions (oxygenation, nutrient, salinity
      and acidification conditions) for different Mediterranean stream types. 116
      potential reference sites located in 23 Mediterranean catchments in Spain were
      sampled in spring, summer and autumn in 2003. All sites were subjected to a
      screening method for the selection of reference sites in Mediterranean streams
      (Mediterranean Reference Criteria) and classified using a pre-established stream
      typology that establishes five different stream types (temporary streams,
      evaporite-calcareous at medium altitude, siliceous headwaters, calcareous
      headwaters and large watercourses). Reference conditions (reference value and
      reference threshold equivalents to high-good class boundary) were calculated
      using two different methods according to the availability of reference sites: the
      reference site 75th percentile approach of all reference sites and the 25th
      percentile of the population approach. The majority of the studied potential
      reference sites (76 out of 116) were selected as reference sites. Regarding type
      specific reference conditions, only siliceous headwaters could be considered
      different from the rest of stream types because lower conductivity and pH. All
      reference stream types presented seasonal differences as regards some parameters,
      except for temporary streams due to the high natural variation of this stream
      type. For those parameters which presented seasonal differences in a specific
      stream type, the least restrictive values were proposed as reference conditions.

PMID- 22386889
TI  - Evaluation of a bacterial algal control agent in tank-based experiments.
AB  - A bacterial-based bioremediation product, LakeReliefTM by Novozymes (Waterguru
      LakeRelief, 2011), was tested in a series of experiments between October 2008 and
      March 2009 to evaluate its suitability as a short-term intervention technique to
      reduce algal blooms in the Swan-Canning River system. Results from fibreglass
      tank experiments (1100 L) suggested that the product did not actively attack and
      lyse algal cells. The product decreased NH(4) and NO(x) concentrations in treated
      tanks, both aerated and non-aerated. Product application decreased PO(4)
      concentrations in non-aerated tanks but not in aerated tanks. The product
      appeared to suppress algal growth in non-aerated tanks over short periods
      (several days). Algal growth regularly diminished after product application but
      reappeared shortly afterwards. Aeration had a negative effect on bacterial
      proliferation in the tanks, possibly through alteration of environmental
      conditions (e.g. water mixing). As a consequence of the environmental conditions
      in the tanks being counterproductive to the development of a representative
      microbial composition, several aspects regarding the product's effectiveness
      could not be assessed satisfactorily in the tank experiments. The importance of
      long-term nutrient immobilisation into a well developed food web and the
      subsequent nutrient removal through removal of the top order organisms is
      highlighted.

PMID- 22386890
TI  - Bundles: an opportunity to align incentives for continuing care in Canada?
AB  - Over the past three decades, diagnosis related groups (DRG) have revolutionized
      hospital funding by successfully focusing hospitals attention on the 'production'
      process. However, using DRG for funding acute hospitals does little to create
      incentives outside of the hospital, or coordinate health care across providers
      and settings. With many health care quality and efficiency issues stemming from
      failures at the 'seams' in the system, there is increasing interest in creating
      new 'bundles' of care which includes acute and post-acute care services that
      align economic incentives for care coordination. Analysis of Ontario (Canada)
      datasets demonstrates that linking existing sources of clinical, administrative
      and cost data to create 'bundles' is technically feasible. However, key
      implementation challenges need to be addressed, such as administrative and
      contractual arrangements across multiple provider organizations, pricing and
      relations with physicians. Nonetheless, this analysis of Ontario data
      demonstrates that bundles provide an alternative policy option to DRG's in
      Canada's move toward activity-based funding.

PMID- 22386891
TI  - Long-term results of adjustable gastric banding in a cohort of 186 super-obese
      patients with a BMI>= 50 kg/m2.
AB  - BACKGROUND: There are conflicting results concerning the bariatric effectiveness
      of adjustable gastric banding in super-obese patients with a Body Mass Index
      (BMI) more or equal to 50 kg/m(2). METHOD: A cohort of 186 patients with a BMI
      greater or equal to 50 kg/m(2) who underwent adjustable gastric banding (AGB) at
      the Bichat-Claude-Bernard University Hospital (Paris, France) were prospectively
      entered into a database. The following data were recorded: BMI, percentage of BMI
      loss, percentage of excess weight lost (%EWL), complications, and surgical re
      interventions. Loss of greater than 50% of excess weight was considered a success
      (primary endpoint). A %EWL of less than 25% after one year, or the removal of the
      gastric band was considered a failure. RESULTS: Thirty-five men (18.8%) and 151
      women (81.2%), with a mean age of 38.9 years (range: 16-65) underwent AGB between
      September 1995 and December 2007. The mean BMI was 55.06 kg/m(2) (range: 50
      74.4). Mean follow-up was 112.5 months with a minimum of 28 months and a maximum
      of 172 months. The follow-up rate was maintained at 89% at ten years. The
      technique of AGB was by "peri-gastric dissection" in the first 115 patients
      (61.82%) and by "pars flaccida dissection" in 71 patients (38.17%). The gastric
      band was removed in 87 of 186 patients (46.8%); band ablation was due to a
      complication of the gastric band in 62 of these cases (33.3%), to failure of
      weight loss in 23 cases (12.4%), and to patient request in two cases (1%). The
      major complications requiring re-operation were: chronic dilatation of the
      proximal gastric pouch (27 patients - 14.5%), acute dilatation (21 patients -
      11.3%), intragastric migration of the prosthesis (six patients - 3.2%), reflux
      esophagitis (six patients - 3.2%), infection of the gastric band (one patient -
      0.5%), and Barrett's esophagus (one patient - 0.5%). No statistically significant
      difference was found between the two operative techniques with regard to the
      possibility of preserving the gastric band for ten years. For patients who
      underwent band removal, no further follow-up analysis of patient data after band
      ablation was performed. The results were best at two years after AGB with a
      median BMI of 42.72 kg/m(2), a band removal rate of 8.6% (16 of 186 patients),
      and a failure rate of 16.4% (28 of 170 patients) of those patients who still had
      their band in place. However, at 10 years, the picture was completely reversed
      with a band removal rate of 52.2% (47 of 90 patients), a failure rate of 22%
      (seven of 33 patients) of those who still had their band in place, and a median
      BMI of 43.43 kg/m(2). CONCLUSION: Laparoscopic gastroplasty using the adjustable
      gastric band appeared to be a promising intervention for super-obese patients
      when the results at two years were analyzed - fairly simple to perform, with
      perioperative morbidity and mortality near zero. However, these results do not
      persist in the long-term for super-obese patients. At ten years, only 11% of
      patients (nine of 80) have successful bariatric results (%EWL>50%) and we were
      forced to remove the gastric band in 52.2% of patients (47 of 90) because of
      complications, regardless of the initial operative technique used. Given these
      results, AGB gastroplasty is not a recommended method for super-obese patients
      and we believe that a BMI greater or equal to 50 kg/m(2) is a contra-indication
      for this procedure.

PMID- 22386892
TI  - Lymphomas of the upper GI tract: the role of radiotherapy.
AB  - The most common site of extra-nodal non-Hodgkin's lymphoma (NHL) is the
      gastrointestinal tract, of which the stomach is the most common site. With the
      exception of extra-nodal marginal zone lymphoma of gastric mucosa-associated
      lymphoid tissue (MALT), where excellent long term results can be achieved by
      radiotherapy, the published literature lacks high quality studies evaluating the
      role, optimal dose and technique of such treatment in the management of gastro
      intestinal lymphoma. Non-randomised studies support organ preservation and a role
      for local radiotherapy in gastric lymphoma.

PMID- 22386893
TI  - QST in peripheral nerve injury pain disorders.

PMID- 22386894
TI  - Vanguard research in opioid-induced hyperalgesia - but guard the basics.

PMID- 22386896
TI  - Regulatory T cells in stem cell transplantation: main characters or walk-on
      actors?
AB  - Almost 10 years have passed since the first experiments specifically addressing
      the role of regulatory T cells (Treg) in stem cell transplantation (SCT). It is
      now time to try to dissect what is their actual impact in such a therapeutic
      context. In the present review we will initially remind the preliminary
      experiments exploring the Treg behavior in murine models of SCT, then moving to
      the first studies evaluating their influence on graft versus host disease and
      graft versus leukemia in humans. After focusing on some interesting aspects of
      Treg mechanisms of action after SCT, we will evaluate their activity after donor
      lymphocyte infusion as well as after reduced intensity conditioning and
      autologous SCT. We will conclude by briefly discussing possible therapeutic
      applications of Treg and highlighting biological and clinical issues which
      deserve to be further assessed in the next future.

PMID- 22386895
TI  - More educated emergency department patients are less likely to receive opioids
      for acute pain.
AB  - Inadequate treatment of pain in United States emergency departments (EDs) is
      common, in part because of the limited and idiosyncratic use of opioids by
      emergency providers. This study sought to determine the relationship between
      patient socioeconomic characteristics and the likelihood that they would receive
      opioids during a pain-related ED visit. We conducted a cross-sectional analysis
      of ED data obtained as part of a multicenter study of outcomes after minor motor
      vehicle collision (MVC). Study patients were non-Hispanic white patients between
      the ages of 18 and 65 years who were evaluated and discharged home from 1 of 8
      EDs in 4 states. Socioeconomic characteristics include educational attainment and
      income. Of 690 enrolled patients, the majority had moderate or severe pain (80%).
      Patients with higher education attainment had lower levels of pain, pain
      catastrophizing, perceived life threat, and distress. More educated patients were
      also less likely to receive opioids during their ED visit. Opioids were given to
      54% of patients who did not complete high school vs 10% of patients with post
      college education (chi(2) test P<.001). Differences in the frequency of opioid
      administration between patients with the lowest educational attainment (39%, 95%
      confidence interval 22% to 60%) and highest educational attainment (13%, 95%
      confidence interval 7% to 23%) remained after adjustment for age, sex, income,
      and pain severity (P=.01). In this sample of post-MVC ED patients, more educated
      patients were less likely to receive opioids. Further study is needed to assess
      the generalizability of these findings and to determine the reason for the
      difference.

PMID- 22386897
TI  - An electronic walkway can predict short-term fall risk in nursing home residents
      with dementia.
AB  - OBJECTIVES: To evaluate the feasibility and validity of gait parameters measured
      with an electronic walkway system in predicting short-term fall risk in nursing
      home residents with dementia. METHODS: 57 ambulatory nursing home residents with
      moderate to severe dementia participated in this prospective cohort study. We
      used the GAITRite((r)) 732 walkway system to assess gait parameters. Measurements
      were collected every 3 months over a 15 month period, with each measurement being
      a baseline for the subsequent measurement. Falls were retrieved from incident
      reports. The predictive validity of the GAITRite((r)) parameters was expressed in
      terms of sensitivity and specificity. Logistic regression analysis was conducted
      to examine the association between these parameters and falls occurrence within
      three months. RESULTS: Reduced velocity (OR=1.22; 95% CI 1.04-1.43) and reduced
      mean stride length (OR=1.19; 95% CI 1.03-1.40) were the best significant gait
      predictors of a fall within three months, with a sensitivity of 82% for velocity
      and 86% for mean stride length, and a specificity of 52% for velocity and for
      mean stride length. The test procedure took an average of 5 min per participant.
      Some verbal persuasion or physical cueing was necessary in 142 measurements
      (80.7%). CONCLUSION: Gait parameters as measured with an electronic walkway
      system can be used for the prediction of short-term fall risk in nursing home
      residents with moderate to severe dementia. However some form of persuasion might
      be needed to perform the task. To refine our findings, large prospective studies
      on the predictive validity of gait parameters in this type of population are
      needed.

PMID- 22386898
TI  - Endovascular treatment of tandem occlusions of the anterior cerebral circulation
      with solitaire FR thrombectomy system. Initial experience.
AB  - PURPOSE: The optimal treatment in the acute phase of cervical internal carotid
      occlusion associated with intracranial obstruction is a matter of debate. In this
      study, we report our experience using the Solitaire FR revascularization device
      and synchronous intravenous fibrinolysis. The distal occlusion was treated with
      Solitaire FR before the proximal one in all cases, a technique not reported so
      far in the literature. METHODS: We examined all cases of tandem occlusion treated
      in our institution between November 2009 and November 2010. The proximal
      occlusion was treated using manual thromboaspiration in order to achieve
      intracranial recanalization as rapid as possible. When necessary, stenting was
      performed after the reconstitution of the intracranial vessel. Morphological and
      clinical results were recorded in the immediate post-operative phase and at the
      three-month follow-up. Clinical success was defined as a mRS at 3 months<=2.
      RESULTS: Four male and six female patients were treated (mean age 66 years). The
      cervical carotid was recanalized in all cases and the intracranial vessel
      (TICI>=2b) in eight. Adverse events were recorded in four patients of which three
      were asymptomatic. These included two cases of subarachnoid hemorrhage, one case
      of traumatic dissection, and one case of fatal intra-cerebral hemorrhage seven
      days following the procedure. At the three-month follow-up a mRS<=2 was observed
      in four patients. CONCLUSIONS: The described approach for the treatment of tandem
      occlusions is promising with regard to both morphological and clinical
      assessments and thus may be considered a valid tool in acute stroke.

PMID- 22386899
TI  - Reversion of transcallosal interhemispheric neuronal inhibition on motor cortex
      after contralateral C7 neurotization.

PMID- 22386900
TI  - Cranial polyneuropathy associated with vertebrobasilar dolichoectasia.

PMID- 22386901
TI  - Combined open decompressive laminectomy and vertebroplasty for treatment of
      thoracolumbar fractures retrospective review of 41 cases.
AB  - BACKGROUND: Vertebral compression fractures are common, and can occur
      concomitantly in patients with symptomatic degenerative stenosis. Less commonly,
      complicated vertebral body fractures may involve retropulsion of bone into the
      spinal canal, resulting in stenosis with myelopathy and/or radiculopathy.
      Decompression of the neural elements can lead to destabilization and progressive
      kyphotic deformity. Laminectomy combined with open vertebroplasty provides a way
      to decompress the neural elements and stabilize the anterior columns in patients
      who cannot tolerate extended surgical time or complications associated with
      instrumentation and fusion. The authors describe the combination of decompressive
      laminectomy and open transpedicular vertebroplasty as a means to decompress
      neural elements and simultaneously stabilize the anterior vertebral column.
      METHODS: Forty-one patients with a total of 51 thoracolumbar fractures were
      included in this retrospective case review. A decompressive laminectomy was
      performed first, followed by vertebroplasty using an open transpedicular
      approach. For subjective assessment of outcome, the patients were assessed using
      the Oswestry Low Back Disability Questionnaire and additional questions
      pertaining to the patient's condition. RESULTS: Out of 51 fractures, there were
      15 burst fractures and 36 compression fractures. Fracture levels ranged from T12
      to S1. The average follow-up period was 27 months (range, 0.5-60 months). The
      mean post-operative Oswestry score was 16 (range, 0-39), and all patients except
      for one were subjectively pleased with the results of the procedure and said they
      would recommend it to others. All patients were able to return to all routine
      activities of daily living. CONCLUSIONS: The authors' cases indicate combining
      open decompressive laminectomies with vertebroplasty can be an effective
      treatment for patients with complicated thoracic and lumbar fractures without
      involving bone fusion or spinal instrumentation and with good long-term outcomes.

PMID- 22386902
TI  - Spinal cord infarction associated with subarachnoid hemorrhage.

PMID- 22386903
TI  - Reduced parietal activation in cervical dystonia after parietal TMS interleaved
      with fMRI.
AB  - OBJECTIVE: Clinically normal hand movement with altered cerebral activation
      patterns in cervical dystonia (CD) may imply cerebral adaptation. Since impaired
      sensorimotor integration appears to play a role in dystonia, left superior
      parietal cortex modulation with repetitive transcranial magnetic stimulation
      (TMS) was employed to further challenge adaptation mechanisms reflected by
      changes in cerebral activation. METHODS: Seven CD patients and ten healthy
      controls were scanned on a 3T magnetic resonance imaging (MRI) scanner with 1 Hz
      inhibitory interleaved TMS. They executed and imagined right wrist
      flexion/extension movements. Each task was preceded by a 10-s period with or
      without TMS. RESULTS: The activations of both tasks after TMS in controls showed
      a similar pattern as found in CD without TMS, i.e. activation increases in
      bilateral prefrontal and posterior parietal regions during both tasks and
      decreases in right anterior parietal cortex during imagery (P<0.001). the
      activations of both tasks after TMS in CD were weaker but with a similar trend in
      activation changes. Only in the right angular gyrus, TMS significantly failed to
      induce an activation increase in CD as was seen in the controls (P<0.001).
      CONCLUSION: The similarity between TMS effects on the distribution of cerebral
      activations in controls and the pattern seen in CD may support the concept that
      CD make use of compensatory circuitry enabling clinically normal hand movement.
      The fact that a similar but weaker TMS effect occurred in CD could suggest that
      the capacity of compensation is reduced. Particularly for the right angular
      gyrus, this reduction was statistically significant.

PMID- 22386904
TI  - [Prolonged hospitalization versus home management for women with arrested preterm
      labour: a before-after study].
AB  - OBJECTIVES: To compare gestational age at birth and incidence of preterm birth
      inferior to 37 weeks of gestation (WG) in single pregnancies with either
      prolonged hospitalization, or early home discharge after arrested preterm labour.
      PATIENTS AND METHODS: Management of preterm labour was changed in our public
      academic hospital because no evidence of benefits for prolonged hospitalization
      was found and because adverse effects related to long-term hospitalization were
      described. In this retrospective before-after study, we compare the attitude A
      (December 2006 to April 2008), a prolonged hospitalization until 32 or 34WG, with
      new attitude B (May 2008 to February 2010), an early discharge home if the
      cervical exam was unchanged since admission. RESULTS: A total of 140 patients
      were included: 70 in each group. Initial hospitalization stay was significantly
      shorter in Group B (respectively, 5.4+/-5.4 days and 11.4+/-12.1 days; P<0.05).
      Preterm spontaneous delivery is 14 (20%) in group A and 21 (28.6%) in Group B
      (P>0.05). Gestational ages at birth were 33(5/7) and 33(0/7) WG in groups A and
      B, respectively (P>0.05). If we focus on patients who were discharged home in the
      two groups (women who did not deliver no matter the hospitalization length), the
      gestational age at birth (38(4/7) and 38WG; ns) and the prematurity rate inferior
      to 37WG (17.2% and 22.4%; ns) were statistically similar. DISCUSSION AND
      CONCLUSION: This study suggests that shorter hospitalization does not decrease
      the delivery term, nor does it increase the premature delivery incidence.

PMID- 22386905
TI  - [Freezing effects on the in vitro development of mice preantral follicles].
AB  - OBJECTIVES: Comparison of in vitro development, survival and oocyte maturation
      rates of mice preantral follicles frozen by various methods. MATERIALS AND
      METHODS: Cryopreservation of the germinal cells using the slow freezing method
      for entire ovary (Ova Cong) or isolated preantral follicles (Iso Cong) and
      vitrification in a closed system of isolated preantral follicles (Iso Vitr). Non
      freezing follicles were considered as the control group. The four groups were
      simultaneous cultured for 12 days in a microdrop system. At each day of the
      culture, mean diameter was measured and at the end of the culture, follicular
      survival and mature oocyte rates were compared. RESULTS: Iso Cong and Ova Cong
      follicles achieved a smaller diameter (423.0 +/- 47.1 MUm et 450.3 +/- 15.7 MUm,
      respectively) than control group (680.7 +/- 12.3 MUm) at the 12th day of culture.
      At the end of the culture 6.21 % of Iso Cong follicles, 53.41 % of Ova Cong
      follicles and 83,77 % of Control follicles were alive. Mature oocyte rates were
      similar for the cryopreserved groups, 44.4 % for Iso Cong group and 44.7 % for
      Ova Cong group, but smaller than the Control group with 90 % of mature oocytes.
      Only 1/171 of the Iso Vitr follicles survived to the culture. DISCUSSION AND
      CONCLUSIONS: This study shows that mice's ovarian follicles can grow in vitro
      after cryopreservation but their diameter, survival and oocytes maturation rates
      are smaller than in the control group.

PMID- 22386906
TI  - [Bacteriospermia in Assisted Reproductive Techniques: effects of bacteria on
      spermatozoa and seminal plasma, diagnosis and treatment].
AB  - The presence of bacteria in semen could induce impairment of sperm morphology,
      alteration of sperm function and mechanical or functional obstruction of the
      seminal tract. The term of bacteriospermia does not signify infection.
      Bacteriospermia and male accessory gland infection (MAGI) have indeed to be
      distinguished. They may lead both to male infertility but their diagnosis and
      treatment options differ. This review summarizes effects of bacteria and
      leucocytospermia on sperm parameters and functions. Then, indications, benefits
      and risks of treatment of bacteriospermia and MAGI, in assisted reproductive
      techniques (ART) will be discussed. For bacteria commonly observed in semen, this
      review aims at defining some thresholds above which a treatment is required.
      These thresholds were established according to literature, according to French
      microbiology society and in function of our usual practice. This review should
      help practitioners of reproductive medicine to take care of bacteriospermia in
      semen.

PMID- 22386907
TI  - [Preserving one's oocytes for the future: myth or reality?].

PMID- 22386908
TI  - Lights out! It is time for bed. Warning: obstructive sleep apnea increases risk
      of sudden death in people with epilepsy.

PMID- 22386909
TI  - The inhibition of aldose reductase on mucus production induced by interleukin-13
      in the human bronchial epithelial cells.
AB  - This study investigated whether aldose reductase (AR) inhibition affects
      interleukin (IL)-13-induced mucus production in the human bronchial epithelial
      cell line-16 (HBE16) cells. The HBE16 cells were cultured with AR inhibitors
      (zopolrestat) or were transfected with an AR small interfering (si)RNA.
      Subsequently, the cells were stimulated with 10 ng/ml IL-13 for 2h. The levels of
      mucin (MUC)5AC mRNA and protein were measured by using RT-PCR or ELISA.
      Intracellular reactive oxygen species (ROS) were measured fluorimetrically with
      the CM-H2DCFDA probe. Western blotting was performed to determine the levels of
      AR, phosphorylated signal transducer and activator of transcription 6 (p-STAT6)
      and phosphorylated Janus kinase 2 (p-JAK2). The results show that treatment with
      zopolrestat or transfection with AR siRNA significantly suppressed IL-13
      stimulated MUC5AC mRNA and protein in the HBE16 cells (P<0.05). AR inhibition
      could suppress IL-13-induced ROS generation, the phosphorylation of JAK2/STAT6
      pathway and the activation of nuclear factor (NF)-kappa B, thereby decreasing
      mucus production in vitro (all P<0.05). Therefore, the inhibition of AR could be
      a therapeutic target for mucus hypersecretion in chronic inflammation lung
      disease.

PMID- 22386910
TI  - Anti-Abeta-MAb and dually decorated nanoliposomes: effect of Abeta1-42 peptides
      on interaction with hCMEC/D3 cells.
AB  - Anti-Abeta-MAb (Abeta-MAb)-decorated immunoliposomes (LIP) and dually decorated
      ones (dd-LIP) with OX-26 and Abeta-MAb were constructed. In both cases, the
      biotin-streptavidin ligation method was applied. All LIP types were characterized
      for size distribution, zeta potential, and integrity during incubation with serum
      proteins. Uptake and transcytosis of both LIP types and control vesicles by human
      brain endothelial hCMEC/D3 cells were measured. All LIP types had mean diameters
      below 150-200 nm and low polydispersity. Abeta-MAb-LIP uptake was higher than
      control PEGylated liposomes, while uptake of dd-LIP was similar to that of OX-26
      LIP. Abeta-MAb-LIP and dd-LIP uptake increased significantly when cells were pre
      incubated with Abeta1-42 peptides; OX-26-LIP uptake was not modulated.
      Transcytosis of Abeta-MAb-LIP through monolayers was 2.5 times higher when
      monolayers were pre-incubated with Abeta1-42. Transport of both probes, FITC
      dextran and rhodamine-lipid, was equivalent, indicating that Abeta-MAb-LIP are
      transferred intact through the BBB model. The Abeta peptide-induced increase in
      binding (and transport) is regulated by the membrane receptors for Abeta1-42
      peptides (RAGE), as proven after blocking RAGE by a specific MAb. Abeta1-42
      peptides did not modulate the barrier tightness and integrity, as determined by
      transendothelial resistance and Lucifer Yellow permeability. Additionally,
      hCMEC/D3 cell viability was not affected by Abeta peptides or by Abeta-MAb-LIP.

PMID- 22386911
TI  - Bioadhesive pellets increase local 5-aminosalicylic acid concentration in
      experimental colitis.
AB  - Topical delivery of 5-aminosalicylic acid (5-ASA) to the colonic mucosa is
      important in order to achieve effective drug concentration in the site of
      inflammation and to minimize its systemic availability. 5-ASA loaded pellets were
      prepared by an extrusion/spheronization method. Mucoadhesive biopolymer chitosan
      was incorporated into the pellets, and drug delivery to the colon was controlled
      by the pH-sensitive polymer Eudragit(r) FS. Dissolution profiles of coated
      pellets revealed no drug release at pH 1.2 within 2h and release as intended in
      the simulated distal ileum and colon. In vivo, chitosan-core drug loaded pellets
      (AMCh) showed 2.5-fold higher drug metabolite concentration than after chitosan
      free pellets (AM) administration in the inflamed colonic tissue. Additionally,
      AMCh demonstrated decreased in AUC in colitis group (1507 +/- 400 ng h/ml)
      compared with AM (1907 +/- 122 ng h/ml). In terms of therapeutic efficiency,
      administration of pellets markedly decreased the colon/body weight ratio
      (colitis: 0.0355 +/- 0.0028; AM 0.0092 +/- 0.0033; AMCh 0.0086 +/- 0.0022) and
      myeloperoxidase activity (colitis: 3212 +/- 294 U/g tissue; AM 796 +/- 211 U/g;
      AMCh 552 +/- 319 U/g). Bioadhesive chitosan pellets showed additional beneficial
      properties for colonic 5-ASA delivery in the treatment of inflammatory bowel
      disease by increasing the drug concentration locally.

PMID- 22386912
TI  - Systematic review and case series of neuropsychological functioning after
      epilepsy surgery in children with dysembryoplastic neuroepithelial tumors (DNET).
AB  - RATIONALE: The purposes of this study were to 1) conduct a review of
      neuropsychological (NP) outcomes after epilepsy surgery for DNET and 2) present
      pre/post-surgical NP results from a series of children with DNET. METHODS: First,
      a systematic literature review was conducted with specific inclusion criteria.
      Second, a review of DNET surgical patients seen at two tertiary-care hospitals
      using reliable change methods of NP functioning was conducted. RESULTS: Of 300
      citations retrieved, 7 studies met criteria. Studies reported low average to
      average pre-surgical IQ. Engel Class I outcome was approximately 85%. CASE
      SERIES: Thirteen children completed pre/post-surgical NP assessments. Pre
      surgically, children demonstrated low average to average functioning. Post
      surgically, few patients showed reliable change. One-third of children
      demonstrated psychological improvement. CONCLUSIONS: NP outcome following DNET
      has not been well-described. Children with DNET demonstrate low average to
      average NP functioning pre-surgically, good seizure outcome, and stable NP
      functioning post-surgically.

PMID- 22386913
TI  - Understanding patient perceptions following a psycho-educational intervention for
      psychogenic non-epileptic seizures.
AB  - This study formed part of an evaluation of a brief educational intervention for
      patients with psychogenic non-epileptic seizures (PNES). The sessions provide
      information, seizure control techniques and management planning. The qualitative
      component of the research reported here aimed to provide insight into the
      participants' perceptions following the intervention. Semi-structured interviews
      were conducted with twelve patients. Interviews were tape-recorded, transcribed
      and analyzed, using principles of thematic analysis. Six key themes were
      identified: getting answers; understanding the link with emotions; seeking a
      physiological explanation; doubting the diagnosis; the role of medication; and
      finding a way forward. The findings highlight considerable individual variation
      in response, with evidence of changed perceptions or enhanced understanding in
      some patients while others continued to seek answers or explanations about the
      cause of their seizures. There were no clear links between reported improved
      understanding or acceptance of the diagnosis and a perceived improvement in the
      condition.

PMID- 22386914
TI  - Functional radiographic analysis of thoracic spine extension motion in
      asymptomatic men.
AB  - OBJECTIVE: The purposes of this study were to examine the range of thoracic spine
      extension motion in a group of young, asymptomatic subjects and compare the
      radiologically derived measurements with those obtained using photographic
      analysis, and to examine the relationship between the magnitude of the neutral
      thoracic kyphosis and the range of thoracic spine extension motion. METHODS: In
      14 asymptomatic male subjects (mean age +/- SD, 30.2 +/- 7 years), the thoracic
      kyphosis in standing and full thoracic spine extension was measured from lateral
      thoracic spine radiographs and digital photographs. The difference between the 2
      measurements was used to define the range of thoracic extension motion. RESULTS:
      The range of thoracic extension motion measured radiologically was between 0 and
      26 degrees  (mean +/- SD, 12.0 degrees  +/- 8.9 degrees ), whereas the
      photographic range was between 8 degrees  and 23 degrees  (mean +/- SD, 12.4
      degrees  +/- 4.1 degrees ). There was a significant correlation between the
      photographic and radiographic measurements of extension range (r = 0.69, P <
      .01). Extension range of motion measured radiologically was significantly
      correlated with the magnitude of the thoracic kyphosis (r = 0.71, P < .01).
      CONCLUSION: Functional radiographs of the thoracic spine can be used to measure
      the extension range of motion and define the extreme of range. The range of
      thoracic extension motion may be influenced by the magnitude of the neutral
      kyphosis. This technique may be used in future studies to evaluate the impact of
      spinal disorders on thoracic spine mobility.

PMID- 22386915
TI  - Chiropractic episodes and the co-occurrence of chiropractic and health services
      use among older Medicare beneficiaries.
AB  - OBJECTIVE: The purpose of this study was to define and characterize episodes of
      chiropractic care among older Medicare beneficiaries and to evaluate the extent
      to which chiropractic services were used in tandem with conventional medicine.
      METHODS: Medicare Part B claims histories for 1991 to 2007 were linked to the
      nationally representative survey on Assets and Health Dynamics among the Oldest
      Old baseline interviews (1993-1994) to define episodes of chiropractic sensitive
      care using 4 approaches. Chiropractic and nonchiropractic patterns of service use
      were examined within these episodes of care. Of the 7447 Assets and Health
      Dynamics among the Oldest Old participants, 971 used chiropractic services and
      constituted the analytic sample. RESULTS: There were substantial variations in
      the number and duration of episodes and the type and volume of services used
      across the 4 definitions. Depending on how the episode was constructed, the mean
      number of episodes per chiropractic user ranged from 3.74 to 23.12, the mean
      episode duration ranged from 4.7 to 28.8 days, the mean number of chiropractic
      visits per episode ranged from 0.88 to 2.8, and the percentage of episodes with
      co-occurrent use of chiropractic and nonchiropractic providers ranged from 4.9%
      to 10.9% over the 17-year period. CONCLUSION: Treatment for back-related
      musculoskeletal conditions was sought from a variety of providers, but there was
      little co-occurrent service use or coordinated care across provider types within
      care episodes. Chiropractic treatment dosing patterns in everyday practice were
      much lower than that used in clinical trial protocols designed to establish
      chiropractic efficacy for back-related conditions.

PMID- 22386916
TI  - Evaluation of patient effective dose from sentinel lymph node lymphoscintigraphy
      in breast cancer: a phantom study with SPECT/CT and ICRP-103 recommendations.
AB  - OBJECTIVE: To evaluate the effective dose delivered to patients undergoing
      sentinel lymph node (SLN) lymphoscintigraphy by taking into account both the
      transmission dose using the CT component of a SPECT/CT system and the (99m)Tc
      internal emission dose. MATERIALS AND METHODS: An adult female humanoid phantom
      and a set of thermoluminescent dosimeters were used in dose measurement from the
      CT transmission irradiation. The choice of measurement organs in the humanoid was
      guided by the recommendations described in the International Commission on
      Radiological Protection report number 103 (ICRP-103). The effective doses due to
      (99m)Tc internal emission source were re-calculated from measurement data
      reported in our previous study on the same subject with the use of tissue
      weighting factors of ICRP-103. RESULTS: CT transmission dose is the main
      contribution to the patient total effective dose for both 1-day and 2-day
      lymphoscintigraphy protocols and for different surgical procedures. Patients
      undergoing SLN lymphoscintigraphy receive about the same amount of total
      effective dose of about 3mSv for both 1-day and 2-day protocol, regardless of
      whether the tissues containing radioactivity would be excised at surgery or not.
      CONCLUSION: Although the total effective dose from using SPECT/CT is equivalent
      to the annual natural background radiation of about 3mSv, nuclear medicine
      physicians should be aware of the increase in effective dose for SLN
      lymphoscintigraphy using hybrid imaging technique of SPECT/CT when compared to
      conventional planar (57)Co flood source for transmission scan. Results from the
      current study provide update information in radiation exposure to patients
      undergoing SLN lymphoscintigraphy with the use of SPECT/CT.

PMID- 22386917
TI  - Parallel mechanisms of epigenetic reprogramming in the germline.
AB  - Germ cells possess the extraordinary and unique capacity to give rise to a new
      organism and create an enduring link between all generations. To acquire this
      property, primordial germ cells (PGCs) transit through an unprecedented programme
      of sequential epigenetic events that culminates in an epigenomic basal state that
      is the foundation of totipotency. This process is underpinned by genome-wide DNA
      demethylation, which may occur through several overlapping pathways, including
      conversion to 5-hydroxymethylcytosine. We propose that the epigenetic programme
      in PGCs operates through multiple parallel mechanisms to ensure robustness at the
      level of individual cells while also being flexible through functional redundancy
      to guarantee high fidelity of the process. Gaining a better understanding of the
      molecular mechanisms that direct epigenetic reprogramming in PGCs will enhance
      our ability to manipulate epigenetic memory, cell-fate decisions and applications
      in regenerative medicine.

PMID- 22386920
TI  - Post-nuclear gene delivery events for transgene expression by biocleavable
      polyrotaxanes.
AB  - A quantitative comparison between nuclear DNA release from carriers and their
      transfection activity would be highly useful for improving the effectiveness of
      non-viral gene vectors. We previously reported that, for condensed DNA particles,
      a close relationship exists between the efficiency of DNA release and
      transfection activity, when biocleavable polyrotaxanes (DMAE-SS-PRX), in which
      the cationic density can be easily controlled. In this study, we first
      investigated the efficiencies of DNA release from condensed DNA particles with
      various types of DMAE-SS-PRX. The findings indicate that an optimal cationic
      density in DMAE-SS-PRX exists for DNA release. We then packaged condensed DNA
      particles in a multifunctional envelope-type nano device (MEND), and evaluated
      their transfection activities. The results showed that the transfection activity
      was increased and this increase was, to some extent, dependent on the efficiency
      of the DNA release. However, transfection activity decreased, when the value for
      the efficiency of DNA release was higher than a certain value. An investigation
      of the fate of intranuclear DNA indicated that a very high efficiency of DNA
      release has a positive influence on transcription, however, it would inhibit the
      post-transcription process; nuclear mRNA export, translation and related
      processes. Such information provides a new viewpoint for the development of
      cationic polymer-based vectors.

PMID- 22386918
TI  - In vivo targeting and positron emission tomography imaging of tumor vasculature
      with (66)Ga-labeled nano-graphene.
AB  - The goal of this study was to employ nano-graphene for tumor targeting in an
      animal tumor model, and quantitatively evaluate the pharmacokinetics and tumor
      targeting efficacy through positron emission tomography (PET) imaging using
      (66)Ga as the radiolabel. Nano-graphene oxide (GO) sheets with covalently linked,
      amino group-terminated six-arm branched polyethylene glycol (PEG; 10 kDa) chains
      were conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid, for (66)Ga
      labeling) and TRC105 (an antibody that binds to CD105). Flow cytometry analyses,
      size measurements, and serum stability studies were performed to characterize the
      GO conjugates before in vivo investigations in 4T1 murine breast tumor-bearing
      mice, which were further validated by histology. TRC105-conjugated GO was
      specific for CD105 in cell culture. (66)Ga-NOTA-GO-TRC105 and (66)Ga-NOTA-GO
      exhibited excellent stability in complete mouse serum. In 4T1 tumor-bearing mice,
      these GO conjugates were primarily cleared through the hepatobiliary pathway.
      (66)Ga-NOTA-GO-TRC105 accumulated quickly in the 4T1 tumors and tumor uptake
      remained stable over time (3.8 +/- 0.4, 4.5 +/- 0.4, 5.8 +/- 0.3, and 4.5 +/- 0.4
      %ID/g at 0.5, 3, 7, and 24 h post-injection respectively; n = 4). Blocking
      studies with unconjugated TRC105 confirmed CD105 specificity of (66)Ga-NOTA-GO
      TRC105, which was corroborated by biodistribution and histology studies.
      Furthermore, histological examination revealed that targeting of NOTA-GO-TRC105
      is tumor vasculature CD105 specific with little extravasation. Successful
      demonstration of in vivo tumor targeting with GO, along with the versatile
      chemistry of graphene-based nanomaterials, makes them suitable nanoplatforms for
      future biomedical research such as cancer theranostics.

PMID- 22386921
TI  - The effects of the modulation of the fibronectin-binding capacity of fibrin by
      thrombin on osteoblast differentiation.
AB  - Fibrin is a natural provisional matrix involved in wound healing and is widely
      utilized for tissue regeneration. The biological performance of fibrin is largely
      dependent on its composition and related structures. In this study, we examined
      the effect of thrombin, which is engaged with fibrin, on osteoblast
      differentiation and its mode of action. Fibrin matrices were prepared with
      different concentrations of thrombin, and MC3T3-E1 pre-osteoblasts were cultured
      on the fibrin matrices. Thrombin-promoted fibrin-enhanced osteoblast
      differentiation in a dose-dependent manner, as confirmed by the extent of calcium
      deposition, alkaline phosphatase activity, and the level of Runx2. The synthetic
      activating peptide of protease-activated receptor 1 (PAR1), a prototype receptor
      of thrombin in osteoblast, did not alter the level of Runx2. Instead, the
      thrombin that was engaged with fibrin in a dose-dependent manner increased the
      phosphorylation of integrins beta1 and beta3. The integrin-blocking peptide RGDS
      reduced the thrombin-enhanced Runx2 in the cells grown on fibrin, whereas the non
      functional peptide RGES did not change the level of Runx2. Furthermore, thrombin
      dose-dependently increased the fibronectin-binding of fibrin. The thrombin
      induced integrin phosphorylation and Runx2 expression were also attenuated
      through the use of a blocking peptide to inhibit the binding of fibronectin to
      fibrin. The results in this study provide evidence that thrombin engaged with
      fibrin accelerates osteoblast differentiation via integrins but not PAR1 by
      modulating the fibronectin-binding capacity of fibrin.

PMID- 22386919
TI  - Macrophage polarization: an opportunity for improved outcomes in biomaterials and
      regenerative medicine.
AB  - The host response to biomaterials has been studied for decades. Largely, the
      interaction of host immune cells, macrophages in particular, with implanted
      materials has been considered to be a precursor to granulation tissue formation,
      the classic foreign body reaction, and eventual encapsulation with associated
      negative impacts upon device functionality. However, more recently, it has been
      shown that macrophages, depending upon context dependent polarization profiles,
      are capable of affecting both detrimental and beneficial outcomes in a number of
      disease processes and in tissue remodeling following injury. Herein, the diverse
      roles played by macrophages in these processes are discussed in addition to the
      potential manipulation of macrophage effector mechanisms as a strategy for
      promoting site-appropriate and constructive tissue remodeling as opposed to
      deleterious persistent inflammation and scar tissue formation.

PMID- 22386883
TI  - 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation
      of atrial fibrillation: recommendations for patient selection, procedural
      techniques, patient management and follow-up, definitions, endpoints, and
      research trial design: a report of the Heart Rhythm Society (HRS) Task Force on
      Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership
      with the European Heart Rhythm Association (EHRA), a registered branch of the
      European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society
      (ECAS); and in collaboration with the American College of Cardiology (ACC),
      American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS),
      and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of
      the American College of Cardiology Foundation, the American Heart Association,
      the European Cardiac Arrhythmia Society, the European Heart Rhythm Association,
      the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the
      Heart Rhythm Society.

PMID- 22386922
TI  - Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty.
AB  - Cellular cardiomyoplasty has been limited by poor graft retention after cell
      transplantation. To ensure good retention of the engrafted cells, a microfluidic
      device was used to fabricate spherical porous beads of poly(D,L-lactic-co
      glycolic acid) as a platform for cell delivery. The beads thus obtained had a
      relatively uniform size, a highly porous structure, and a favorably
      interconnected interior architecture, to facilitate the transportation of oxygen
      and nutrients. These porous beads were loaded with human amniotic fluid stem
      cells (hAFSCs) to generate cellularized microscaffolds. Live/dead assay
      demonstrated that most of the cells in the porous constructs were viable. The
      hAFSCs that were grown in beads formed a complex three-dimensional organization
      with well-preserved extracellular matrices (ECM) according to their porous
      structure. Retention of the administered beads was clearly identified at the site
      of engraftment following an experimentally induced myocardial infarction in a rat
      model. The results of echocardiography, magnetic resonance imaging, and
      histological analyses suggest that the transplantation of hAFSC beads into an
      infarcted heart could effectively maintain its gross morphology, prevent
      successive ventricular expansion, and thereby improve the post-infarcted cardiac
      function. Immunofluorescent staining revealed that the microenvironment that was
      provided by the infarcted myocardium might offer cues for the induction of the
      engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results
      demonstrate that the cellularized beads with endogenously secreted ECM were of
      sufficient physical size to be entrapped in the interstitial tissues following
      transplantation, thereby benefiting the infarcted heart.

PMID- 22386923
TI  - Stage for stage comparison of recurrence patterns after definitive
      chemoradiotherapy or surgery for oesophageal carcinoma.
AB  - AIMS: Definitive chemoradiotherapy (dCRT) has been advocated as an alternative
      treatment for oesophageal carcinoma, but received criticism for perceived poorer
      locoregional disease control when compared with surgery. The aim of this study
      was to determine the relative incidence and pattern of oesophageal carcinoma
      recurrence after dCRT and surgery in patients receiving stage-directed therapy
      with curative intent. MATERIALS AND METHODS: In total, 623 consecutive patients
      with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were
      studied. The primary outcome measure was disease-free survival, adjusted for
      baseline differences in gender, age and histological cell type. RESULTS: Three
      hundred and eleven patients deemed unsuitable for surgery on the grounds of
      performance status (n = 137), bulky local disease (n = 121) or personal choice (n
      = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy).
      Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT
      compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more
      common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In
      contrast, distant metastases were more common after surgery than after dCRT
      (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients
      receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage
      related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6
      versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III
      (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710).
      CONCLUSIONS: These findings provide further support for a randomised trial of
      dCRT versus surgery in both oesophageal squamous cell carcinoma and
      adenocarcinoma.

PMID- 22386924
TI  - Diabetes and mucormycosis: a complex interplay.
AB  - Mucormycosis is a life-threatening invasive fungal infection that arises
      particularly in diabetic patients with or without other underlying conditions
      such as haematological malignancies or the need for solid-organ transplantation.
      Rhino-orbito-cerebral involvement is the primary site of mucormycosis, but the
      paucity of signs may be a cause of delayed diagnosis. Thus, any case of
      documented non-bacteriological sinusitis in diabetic patients, even without
      ketoacidosis, should prompt suspicion of a mucormycosis diagnosis. To optimalize
      information for clinicians in charge of diabetic patients, this extensive review
      of the literature was carried out to provide an overview of mucormycosis
      specificities, epidemiology and pathophysiology in the setting of diabetes.

PMID- 22386925
TI  - The use of prophylactic inferior vena cava filters in trauma patients: a
      systematic review.
AB  - INTRODUCTION: Pulmonary embolisms (PE) are an often preventable cause of late
      morbidity and mortality after trauma. Although there is evidence for the use of
      therapeutic inferior vena cava (IVC) filters (defined as IVC filters implanted in
      those with proven deep venous thrombosis [DVT] in order to prevent PE), there is
      not as much evidence to support the use of prophylactic IVC filters. Thus, we
      undertook a systematic review of the literature to assess the following in
      prophylactic IVC filters: efficacy in PE reduction, prevalence of filter-related
      complications and the indications for use. MATERIALS AND METHODS: After screening
      249 studies, 24 studies met inclusion criteria for qualitative synthesis.
      RESULTS: Overall, the literature is supportive of the use of prophylactic IVC
      filters in high-risk poly-trauma patients who may have contraindications to DVT
      prophylaxis. Filter-associated complications are uncommon and, when they do
      occur, tend to be of limited clinical significance. Limited data, mostly in the
      form of case series, supports a reduction in PE and PE-related mortality. There
      has been increasing use of retrievable filters as well as the ability to safely
      retrieve them at longer intervals. CONCLUSION: Despite the addition of a few
      matched-control studies, the literature is still plagued by a lack of high
      quality data, and therefore the true efficacy of prophylactic IVC filters for
      prevention of PE in trauma patients remains unclear. Further studies are required
      to determine the true role of prophylactic IVC filters in trauma patient.

PMID- 22386926
TI  - Physicians' attitudes about referring their type 2 diabetes patients for
      bariatric surgery.
AB  - BACKGROUND: Despite increasing evidence about the beneficial effects of bariatric
      surgery, little is known about physicians' attitudes toward it as a treatment of
      type 2 diabetes. Our objective was to investigate physicians' attitudes about
      referring patients with type 2 diabetes for bariatric surgery. METHODS:
      Physicians were identified from the Pennsylvania Integrated Clinical and
      Administrative Research Database and other databases. Physicians at an academic
      medical center (n = 142) and community-based physicians (n = 197) in the
      Philadelphia area in specialties likely to treat type 2 diabetes were sent a
      survey about their perceptions of the safety and efficacy of bariatric surgery as
      a treatment for obesity and type 2 diabetes. RESULTS: Of the physicians, 93
      returned the survey, for a combined response rate of 27.4%. Respondents reported
      having positive impressions of bariatric surgery as a treatment for obesity and
      type 2 diabetes (79.6% and 67.4%, respectively). Only 20.8% of respondents
      indicated that they would be likely to refer their patients with type 2 diabetes
      with a body mass index of 30-34.9 kg/m(2) to a randomized research trial of
      bariatric surgery. CONCLUSION: In general, physicians who treat patients with
      type 2 diabetes had favorable impressions about bariatric surgery as a treatment
      for obesity and type 2 diabetes. However, only a few were willing to refer their
      patients with type 2 diabetes and a body mass index of 30-34.9 kg/m(2) to
      randomized research trials of bariatric surgery. This reluctance to refer
      patients represents an important barrier to the successful completion of studies
      of the efficacy of bariatric surgery for those with type 2 diabetes and a body
      mass index <35 kg/m(2).

PMID- 22386927
TI  - Challenging the distribution shift: statically-induced direction illusion
      implicates differential processing of object-relative and non-object-relative
      motion.
AB  - The direction illusion is the phenomenal exaggeration of the angle between the
      drift directions, typically, of two superimposed sets of random dots. The
      direction illusion is commonly attributed to mutual inhibition between direction
      selective cell populations (distribution-shift model). A second explanation
      attributes the direction illusion to the differential processing of relative and
      non-relative motion components (differential processing model). Our first
      experiment demonstrates that, as predicted by the differential processing model,
      a static line can invoke a misperception of direction in a single set of dots--a
      phenomenon we refer to as the statically-induced direction illusion. In a second
      experiment, we find that the orientation of a static line can also influence the
      size of the conventional direction illusion. A third experiment eliminates the
      possibility that these results can be explained by the presence of motion
      streaks. While the results of these experiments are in agreement with the
      predictions made by the differential processing model, they pose serious problems
      for the distribution-shift account of shifts in perceived direction.

PMID- 22386928
TI  - Toxic and recovery effects of copper on Caenorhabditiselegans by various food
      borne and water-borne pathways.
AB  - Copper pollutions are typical heavy metal contaminations, and their ability to
      move up food chains urges comprehensive studies on their effects through various
      pathways. Currently, four exposure pathways were prescribed as food-borne (FB),
      water-borne plus clean food (WCB), water-food-borne (WFB) and water-borne (WB).
      Caenorhabditiselegans was chosen as the model organism, and growth statuses,
      feeding abilities, the amounts of four antioxidant enzymes, and corresponding
      recovery effects under non-toxic conditions with food and without food were
      investigated. Based on analysis results, copper concentrations in exposure were
      significantly influenced by the presence of food and its uptake by C.elegans.
      Both exposure and recovery effects depended on exposure concentrations and food
      conditions. For exposure pathways with food, feeding abilities and growth
      statuses were generally WFB<WCB<=FB (p<0.05). The antioxidant activities were up
      regulated in the same order. Meanwhile, the exposure pathway without food (WB)
      caused non-up-regulated antioxidant activities, and had the best growth statuses.
      For recoveries with food, growth statuses, feeding abilities and the inductions
      of the antioxidant enzymes were all WB~WFB<WCB<FB (p<0.05). For recoveries
      without food, the order of growth statuses remained WB>FB>WCB>WFB (p<0.05), while
      the antioxidant activities were all inhibited in a concentration-dependent
      fashion. In conclusion, contaminated food was the primary exposure pathway, and
      various pathways caused different responses of C.elegans.

PMID- 22386929
TI  - Molecular and physiological approaches to understand the ecology of methanol
      degradation during the biofiltration of air streams.
AB  - A 13.4 L biofilter treating an off-gas stream supplemented with methanol under
      two different situations was studied in terms of MeOH removal efficiency,
      microbial ecology and odor removal. During Period 1 (P1) the reactor was packed
      with wood bark chips with no pH control, treating an off-gas resulting from the
      aerobic chamber of a membrane biological reactor treating sewage and located
      outdoor, whereas during Period 2 (P2) a compressed air stream fed with MeOH was
      treated using PVC rings and maintaining pH at neutral values. Both systems
      operated at 96 g MeOH m(-3) h(-1) achieving removal efficiencies of around 90%
      during P1 and 99.9% during P2. The relative activity of biomass developed in both
      systems was assessed using respirometric analysis with samples obtained from both
      biofilms. Higher biomass activity was obtained during P2 (0.25-0.35 kg MeOH kg(
      1) VSS d(-1)) whereas 1.1 kg MeOH kg(-1) VSS d(-1) was obtained in the case of
      P1. The application of molecular and microscopic techniques showed that the
      eukaryotes were predominant during P1, being the yeast Candida boidinii the most
      abundant microorganism. A specific Fluorescence in situ hybridization probe was
      designed for C. boidinii and tested successfully. As a result of the neutral pH,
      a clear predominance of prokaryotes was detected during P2. Interestingly, some
      anaerobic bacteria were detected such as Desulfovibrio, Desulfobacteraceae
      species and also some archaea such as Methanosarcina.

PMID- 22386930
TI  - The development of LTi cells.
AB  - Lymphoid tissue inducer (LTi) cells are programmed by the mammalian fetus to
      induce the development of lymph nodes and Peyer's patches. LTi cells share a pro
      inflammatory profile with Th17 cells, as well as their requirement for the
      transcription factor RORgammat. We discuss here the latest data on the fetal and
      post-natal development of LTi cells, and their relationship with the larger
      family of innate lymphoid cells (ILCs). We suggest that the re-programming of
      RORgammat in a subset of common lymphoid progenitors allowed mammals to develop
      lymphoid organs before birth, whereas other vertebrates only develop such organs
      in response to infection or injury.

PMID- 22386931
TI  - Serum ferritin levels predict incident non-alcoholic fatty liver disease in
      healthy Korean men.
AB  - Little research has been done to examine the temporal relationship between serum
      ferritin and the development of nonalcoholic fatty liver disease. The aim of this
      study was to examine whether serum ferritin levels predict incident fatty liver
      in non-diabetic men. The study cohort comprised 2410 healthy Korean male who were
      aged 30 to 59years old with no evidence of ultrasonographically detectable fatty
      liver (USFL) at baseline. Alcohol intake was assessed with a self-reported
      questionnaire. At each visit, biochemical and anthropometric measurements and
      abdominal ultrasonography were done. Cox proportional hazard models were used to
      calculate the adjusted hazard ratios in separate models for USFL. During 7545.9
      person-years of follow-up, 586 participants developed USFL. The hazard ratio (95%
      confidence interval) for incident USFL comparing the highest quartile of serum
      ferritin level to the lowest quartile was 1.54 (1.21-1.94) after adjusting for
      age, body mass index, smoking, alcohol intake, and exercise. That association
      remained significant after further adjustment for cardiovascular risk factors and
      in time-dependent models. The association between serum ferritin and incident
      USFL was still significant in the non-overweight group or the no current smoker
      group. Serum ferritin level was an independent risk factor of incident fatty
      liver detected by ultrasonography even in non-obese, healthy Korean men.
      Increased serum ferritin levels appear to be an early predictor for incident
      fatty liver.

PMID- 22386932
TI  - Obesity-insulin targeted genes in the 3p26-25 region in human studies and LG/J
      and SM/J mice.
AB  - Identifying metabolic syndrome (MetS) genes is important for novel drug
      development and health care. This study extends the findings on human chromosome
      3p26-25 for an identified obesity-insulin factor QTL, with an LOD score above 3.
      A focused association analysis comprising up to 9578 African American and
      Caucasian subjects from the HyperGEN Network (908 African Americans and 1025
      whites), the Family Heart Study (3035 whites in time 1 and 1943 in time 2), and
      the Framingham Heart Study (1317 in Offspring and 1320 in Generation 3) was
      performed. The homologous mouse region was explored in an F(16) generation of an
      advanced intercross between the LG/J and SM/J inbred strains, in an experiment
      where 1002 animals were fed low-fat (247 males; 254 females) or high-fat (253
      males; 248 females) diets. Association results in humans indicate pleiotropic
      effects for SNPs within or surrounding CNTN4 on obesity, lipids and blood
      pressure traits and for SNPs near IL5RA, TRNT1, CRBN, and LRRN1 on central
      obesity and blood pressure. Linkage analyses of this region in LG/J*SM/J mice
      identify a highly significant pleiotropic QTL peak for insulin and glucose
      levels, as well as response to glucose challenge. The mouse results show that
      insulin and glucose levels interact with high and low fat diets and differential
      gene expression was identified for Crbn and Arl8b. In humans, ARL8B resides
      ~137kbps away from BHLHE40, expression of which shows up-regulation in response
      to insulin treatment. This focused human genetic analysis, incorporating mouse
      research evidenced that 3p26-25 has important genetic contributions to MetS
      components. Several of the candidate genes have functions in the brain. Their
      interaction with MetS and the brain warrants further investigation.

PMID- 22386933
TI  - Morin attenuates blood pressure and oxidative stress in deoxycorticosterone
      acetate-salt hypertensive rats: a biochemical and histopathological evaluation.
AB  - The present study was designed to evaluate the antihypertensive and antioxidant
      effect of morin, a flavonoid against deoxycorticosterone acetate (DOCA)-salt
      induced hypertension in male Wistar rats. Hypertension was induced in
      uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA
      (25mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. The DOCA
      salt hypertensive rats showed significant (P < .05) increase in the systolic and
      diastolic blood pressure, heart rate, water intake and organ weights (kidney,
      heart, aorta and liver). DOCA-salt hypertensive rats also showed significant (P <
      .05) increase in the levels of thiobarbituric acid reactive substances, lipid
      hydroperoxides and conjugated dienes in plasma and tissues (kidney, heart, aorta
      and liver), and significant (P < .05) decrease in the body weight, nitrite and
      nitrate levels in plasma and heart. Furthermore, the activities of enzymic
      antioxidants such as superoxide dismutase, catalase and glutathione peroxidase in
      erythrocyte and tissues and the levels of non-enzymic antioxidants such as
      reduced glutathione, vitamin C and vitamin E in plasma and tissues were
      significantly (P < .05) decreased in DOCA-salt rats. Morin supplementation
      (50mg/kg) daily for six weeks brought back all the above parameters to near
      normal level. The above findings were confirmed by the histopathological
      examination. No significant (P < .05) effect was observed in UNX-rats treated
      with morin (50mg/kg). These results suggest that morin acts as an
      antihypertensive and antioxidant agent against DOCA-salt induced hypertension.

PMID- 22386934
TI  - Atf6alpha-null mice are glucose intolerant due to pancreatic beta-cell failure on
      a high-fat diet but partially resistant to diet-induced insulin resistance.
AB  - Activating transcription factor 6alpha (ATF6alpha) is essential for the
      endoplasmic reticulum (ER) stress response. Since recent studies suggested that
      ER stress is involved in the pathogenesis of type 2 diabetes mellitus, we have
      analyzed Atf6alpha-null (Atf6alpha(-/-)) mice challenged with metabolic overload
      or genetic manipulations. Atf6alpha(-/-) mice were fed a high-fat diet to create
      diet-induced obese (DO) mice, and were subjected to examination of glucose
      homeostasis with biochemical and morphological analysis of the pancreatic beta
      cell and liver tissues. Atf6alpha-null mice were also crossed with genetic models
      of diabetes caused either by insulin resistance (Agouti obese mice) or by
      impaired insulin secretion (Ins2(WT/C96Y) mice). Atf6alpha(-/-) DO mice were less
      glucose tolerant with blunted insulin secretion compared to littermates on a high
      fat diet. Pancreatic insulin content was lower in Atf6alpha(-/-) DO mice with the
      swollen beta-cell ER, a typical feature of cells with ER stress. In the liver of
      Atf6alpha(-/-) DO mice, XBP-1 splicing was increased, suggesting that higher ER
      stress was present. ATF6-deficient mice showed increased mRNA expressions of
      glucose-6-phosphatase and SREBP1c associated with a tendency for a higher degree
      of steatosis in the liver. However, Atf6alpha(-/-) DO mice exhibited higher
      insulin sensitivity with lower serum triglyceride levels. Similar phenotypes were
      observed in ATF6alpha-deficient Agouti mice. In addition, ATF6alpha-deficiency
      accelerated reduction in pancreatic insulin content in Ins2(WT/C96Y) mice. These
      data suggested that ATF6alpha contributes to both prevention and promotion of
      diabetes; it protects beta-cells from ER stress and suppresses hepatosteatosis,
      but plays a role in the development of hyperlipidemia and insulin resistance.

PMID- 22386936
TI  - Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal
      tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level.
AB  - Advanced glycation end products (AGEs) and their receptor (RAGE) axis play a role
      in diabetic nephropathy. Statins have been shown to ameliorate renal function and
      reduce proteinuria in patients with chronic kidney disease. However, the effects
      of statin on AGEs-induced tubular cell damage remain unknown. We examined here
      whether and how pravastatin could block the AGEs-RAGE-elicited tubular cell
      injury in vitro. Gene expression level was evaluated by real-time reverse
      transcription polymerase chain reactions. Reactive oxygen species (ROS)
      generation was measured with dihydroethidium staining. Apoptosis was analyzed in
      an enzyme-linked immunosorbent assay. Asymmetric dimethylarginine (ADMA)
      expression was evaluated by immunostaining. Pravastatin dose-dependently
      inhibited the AGEs-induced up-regulation of RAGE mRNA level, ROS generation and
      apoptosis in human renal proximal tubular cells. Further, AGEs decreased mRNA
      level of dimethylarginine dimethylaminohydrolase-2, an enzyme that mainly
      degrades asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric
      oxide synthase and subsequently increased ADMA generation in tubular cells, both
      of which were also prevented by pravastatin. Geranylgeranyl pyrophosphate (GGPP)
      treatment blocked all of the effects of pravastatin on tubular cells. We found
      that rosuvastatin also significantly blocked the AGEs-induced increase in RAGE
      mRNA level and ROS generation, both of which were prevented by GGPP. Our present
      study suggests that pravastatin could inhibit the AGEs-induced apoptosis and ADMA
      generation in tubular cells by suppressing RAGE expression probably via
      inhibition of GGPP synthesis. Pravastatin may exert beneficial effects on tubular
      damage in diabetic nephropathy by blocking the AGEs-RAGE axis.

PMID- 22386938
TI  - Sulfated oxysterols as candidates for the treatment of nonalcoholic fatty liver
      disease.

PMID- 22386937
TI  - Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice.
AB  - Adipose tissue macrophages are important mediators of inflammation and insulin
      resistance in obesity. IFN-gamma is a central regulator of macrophage function.
      The role of IFN-gamma in regulating systemic inflammation and insulin resistance
      in obesity is unknown. We studied obese IFN-gamma knockout mice to identify the
      role of IFN-gamma in regulating inflammation and insulin sensitivity in obesity.
      IFN-gamma-knockout C57Bl/6 mice and wild-type control litter mates were
      maintained on normal chow or a high fat diet for 13 weeks and then underwent
      insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry,
      intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte
      phenotype and cytokine expression profiles. Adipocyte size was determined from
      whole adipose tissue explants examined under immunofluorescence microscopy. Diet
      induced obesity induced systemic inflammation and insulin resistance, along with
      a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and
      NK cells. Obese IFN-gamma-knockout animals, compared with obese wild-type control
      animals, demonstrate modest improvements in insulin sensitivity, decreased
      adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These
      data suggest a role for IFN-gamma in the regulation of inflammation and glucose
      homeostasis in obesity though multiple potential mechanisms, including effects on
      adipogenesis, cytokine expression, and macrophage phenotype.

PMID- 22386939
TI  - Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats.
AB  - Ovarian hormones modulate the metabolism of adipose cells and present a
      protective effect against hypertension. The aim of this study was to compare the
      effect of estradiol on adiposity markers in spontaneously hypertensive rats.
      Ovariectomized spontaneously hypertensive rats treated with estradiol (5 MUg/100
      g/day), three weeks after ovariectomy, presented decreased blood pressure and
      insulin levels and increased hepatic glycogen content. Periuterine or mesenteric
      adipocytes from treated animals were smaller as compared to vehicle treated
      group, whereas no differences were observed in relation to the number of cells.
      Basal rates of glycerol release were higher only in periuterine adipocytes of
      treated rats. The increment of glycerol release over basal values in response to
      isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated
      periuterine and mesenteric adipocytes, respectively. The estradiol treated group
      was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis
      than the control animals. The lipoprotein lipase activity decreased after
      treatment, only in periuterine adipose tissue. Estradiol administration increased
      basal and insulin-stimulated rates of glucose transport in adipocytes of both
      sites, although the values obtained by periuterine were higher than those
      observed for mesenteric adipocytes. Both adipose tissues from treated animals
      exhibited a decreased expression of the peroxisome proliferator-activated
      receptor-gamma, but an increased expression of peroxisome proliferator-activated
      receptor-alpha in liver. These findings suggest that estrogen administration
      attenuates adiposity markers of spontaneously hypertensive rats as a result of
      the decreased expression levels of peroxisome proliferator-activated receptor
      gamma in adipose tissue and increased expression of peroxisome proliferator
      activated receptor-alpha in liver.

PMID- 22386940
TI  - Identification and characterization of a novel X-linked AVPR2 mutation causing
      partial nephrogenic diabetes insipidus: a case report and review of the
      literature.
AB  - X-linked nephrogenic diabetes insipidus (NDI) is a rare disease characterized by
      a malfunctioning renal response to the antidiuretic hormone arginine vasopressin
      (AVP) due to mutations in the AVPR2 gene. A limited number of mutations in the
      AVPR2 gene resulting in partial phenotype have been described so far. In this
      mini-review the retrospective analysis of 13 known AVPR2 mutations that have been
      previously shown in vitro to partially abolish AVPR2 function is described, along
      with a novel mutation diagnosed in a kindred with partial NDI. In the present
      study, a 14 year old male and his 73 year old maternal grandfather were diagnosed
      with partial NDI based on the clinical phenotype, the water deprivation test and
      the inadequate response to 1-desamino-8-d-arginine vasopressin (DDAVP)
      administration. Sequencing analysis of the AVPR2 gene revealed the novel missense
      mutation p.N317S (g.1417A > G) in both patients. This mutation was re-created by
      site directed mutagenesis in an AVPR2 cDNA expression vector and was functionally
      characterized, in terms of arginine vasopressin (AVP) and DDAVP response. AVPR2
      activity of the p.N317S mutant receptor after the AVP and DDAVP administration,
      as assessed by cAMP production was reduced and impaired when compared to cells
      that expressed the wild type AVPR2 gene. In conclusion, the affected members of
      this family have X-linked NDI with partial resistance to AVP, due to a missense
      mutation in the AVPR2 gene.

PMID- 22386941
TI  - Podocytes and the struggle against glucose toxicity: new targets for treatment?

PMID- 22386942
TI  - Increased action of pulsatile compared to non-pulsatile insulin delivery during a
      meal-like glucose exposure simulated by computerized infusion in healthy humans.
AB  - It has previously been demonstrated that pulsatile insulin has a greater
      hypoglycemic effect than non-pulsatile insulin during euglycemic conditions. The
      aim of the present study was to examine the effect of pulsatile versus non
      pulsatile insulin delivery during a meal-like iv-glucose challenge. Ten healthy
      young subjects were examined on two occasions. A pancreatic-pituitary clamp was
      maintained with somatostatin infusion and replacement of glucagon and growth
      hormone at baseline levels. During the first three hours on both study days,
      insulin was infused in a pulsatile manner. Hereafter glucose and insulin were
      infused by computer-controlled pumps for four hours in a pattern mimicking the
      postprandial glucose and insulin profiles. At one study day, insulin infusion was
      done in a continuous manner, while at the other study day this profile was done
      in a pulsatile pattern. The hypoglycemic effect of insulin was measured as the
      integrated area under the curve of glucose during the four-hour infusion period.
      The mean insulin concentration measured as the integrated area under the curve
      was identical (P > .9). The hypoglycemic effect of insulin was significantly
      augmented by 13% during pulsatile delivery as compared to continuous delivery (P
      = .015). Likewise was the maximal glucose concentration significantly lower at
      the day of the pulsatile profile (9.9 +/- 1.0 vs. 11.4 +/- 2.3 mmol/l, P = .036).
      Pulsatile insulin release plays an important role in the postprandial glucose
      homeostasis. The disturbed insulin pulsatility in type 2 diabetes mellitus may
      contribute to the postprandial hyperglycemia.

PMID- 22386943
TI  - High tea and vegetable consumption is associated with low ADMA generation in
      older healthy subjects.
AB  - Asymmetric dimethylarginine (ADMA) has been recognized as a marker of
      cardiovascular risk. We sought to investigate whether consumption of tea, coffee,
      fruit or vegetables is associated with ADMA. In 148 consecutive apparently
      healthy subjects (104 men and 44 women aged 40 to 70), daily tea, coffee, fruit
      and vegetable consumption was ascertained by questionnaire. Plasma ADMA,
      symmetric dimethylarginine (SDMA), and l-arginine levels were measured by high
      performance liquid chromatography. Median tea and coffee consumption was 2
      cups/d, while vegetable and fruit intake was 152 (120-179)g/d and 120 (108
      134)g/d, respectively. Median plasma ADMA, SDMA and arginine were 0.47 (0.43
      0.53)MUmol/L, 0.59 (0.54-0.66)MUmol/L and 86 (68-101)MUmol/L, respectively. ADMA
      correlated inversely with tea (r = -0.70, P < .0001) and vegetable consumption (r
      = -0.50, P < .0001) even after adjustment for age, sex, body mass index, smoking
      status, and potential dietary and biochemical parameters. No association between
      ADMA and fruit consumption was found. ADMA correlated positively with coffee
      intake (r = 0.37, P < .0001), although these associations were less potent after
      adjustment for dietary factors. Higher tea and vegetable intake is associated
      with lower plasma ADMA levels in healthy middle-aged subjects.

PMID- 22386944
TI  - Kwashiorkor and marasmus are both associated with impaired glucose clearance
      related to pancreatic beta-cell dysfunction.
AB  - Severe malnutrition is a major health problem in developing countries and can
      present as kwashiorkor or marasmus. Kwashiorkor is associated with septicaemia,
      profound metabolic changes including hepatic steatosis, altered protein
      metabolism and increased oxidative stress. Limited data suggest that children
      with kwashiorkor have an impaired glucose tolerance and insulin secretion. Our
      objective was to determine glucose tolerance in children with kwashiorkor
      compared to marasmus and its relation to insulin secretion and sensitivity. Six
      children with kwashiorkor and 8 children with marasmus were studied. We were also
      able to include 3 healthy children for comparison. They received a primed (13
      mg/kg), constant infusion (0.15 mg/kg/min) of [6,6-(2)H(2)]glucose for 4 h with
      serial blood sampling. In addition, an oral glucose tolerance test (OGTT) was
      performed with labeled 10 mg/g [U-(13)C]glucose. Glucose clearance was determined
      using mathematical modeling. Glucose clearance rates during the OGTT were -392
      (range 309) mL/kg in children with kwashiorkor, -156 (426) mL/kg in marasmus and
      279 (345) mL/kg in the control group. Glucose clearance rates correlated with
      plasma albumin concentrations (r=0.67, P=.001). Insulin responses were strongly
      impaired in both kwashiorkor and marasmus. There was no indication of peripheral
      or hepatic insulin resistance in the malnourished groups. We show that glucose
      clearance rates are affected in both children with marasmus as well as
      kwashiorkor, which correlate with plasma albumin concentrations. The disturbed
      glucose clearance in malnutrition is related to an impairment in insulin
      availability.

PMID- 22386945
TI  - Binding of peptides corresponding to the carboxy-terminal region of human-beta
      defensins-1-3 with model membranes investigated by isothermal titration
      calorimetry.
AB  - Human-beta-defensins HBD-1-3 are important components of the innate immune
      system. Synthetic peptides Phd-1-3 with a single disulphide bond, spanning the
      cationic C-terminal region of HBD-1-3, have antimicrobial activity. The
      interaction of Phd-1-3 with model membranes was investigated using isothermal
      titration calorimetry (ITC) and steady-state fluorescence polarization to
      understand the biophysical basis for the mechanism of antimicrobial action.
      Calorimetric titration of POPE:POPG (7:3) vesicles with peptides at 25 degrees C
      and 37 degrees C showed complex profiles with two distinct regions of heat
      changes. The data indicate binding of Phd-1-3 at 37 degrees C to both negative
      and zwitterionic lipid vesicles is exothermic with low enthalpy values (DeltaH~
      1.3 to -2.8kcal/mol) as compared to amphipathic helical antibacterial peptides.
      The adsorption of peptides to negatively charged lipid membranes is modulated by
      electrostatic interactions that are described by surface partition equilibrium
      model using Gouy-Chapman theory. However, this model could not explain the
      isotherms of peptide binding to zwitterionic lipid vesicles. Fluorescence
      polarization of TMA-DPH (1-[4-(trimethylammonio) phenyl]-6-phenyl-1,3,5
      hexatriene) and DPH (1,6-diphenyl-1,3,5-hexatriene) located in the head group and
      acyl chain region respectively, indicates that the peptides interact with
      interfacial region of negatively charged membranes. Based on the results
      obtained, we conclude that adsorption of cationic peptides Phd-1-3 on lipid
      surface do not result in conformational change or pore formation. It is proposed
      that interaction of Phd-1-3 with the negatively charged lipid head group causes
      membrane destabilization, which in turn affects the efficient functioning of
      cytoplasmic membrane proteins in bacteria, resulting in cell death.

PMID- 22386946
TI  - Cavitation-induced radical-chain oxidation of valeric aldehyde.
AB  - The application of high-amplitude ultrasound to liquids triggers cavitation. By
      the collapse of the thereby appearing vacuum cavities, high temperatures can be
      reached in a transient manner. The high temperatures in these hot-spots can lead
      to homolytic scission of chemical bonds. The thereby generated radicals are
      usually utilized in aqueous systems for the degeneration of organic pollutants.
      In this contribution, we demonstrate that the radicals can also be used for
      synthetic purposes: under an oxygen atmosphere, they trigger the oxidation of an
      aldehyde substrate.

PMID- 22386947
TI  - Incidence, risk factors and management of delayed wound dehiscence after
      craniotomy for tumor resection.
AB  - Dehiscence after a wound has healed is a known complication of craniotomy for
      tumor resection. We conducted a retrospective analysis of 64 patients who
      underwent craniotomy for tumor resection followed by radiation or radiosurgery
      between 2006 and 2010. Five patients (7.8%) were identified who showed wound
      dehiscence from two to eight months after the craniotomy wound had healed. Four
      patients had previously undergone additional craniotomies, additional
      radiosurgery or had been treated with the anti-angiogenic factor, bevacizumab.
      These treatments may be risk factors for developing delayed dehiscence and, in
      combination, may potentiate local wound healing problems. Potential mechanisms
      and management strategies are discussed.

PMID- 22386948
TI  - Continuous in vitro cultivation of a recently identified Babesia that infects
      small ruminants in China.
AB  - Babesia sp. Xinjiang was isolated from a splenectomised sheep infested by
      Rhipicephalus sanguineus and Hylomma anatolicum anatolicum, collected from sheep
      and cattle in Xinjiang province. It was considered to be a novel ovine Babesia
      species on the basis of its morphology, pathogenicity, vector tick species and
      alignments of 18S ribosomal RNA (18S rRNA) and internal transcribed spacers (ITS)
      gene sequences. Continuous in vitro cultures of the ovine parasite were
      established using infected sheep blood. In RPMI 1640 medium with 7.5% sheep red
      blood cells (RBCs) maintained in an incubator at 37  degrees C and 5% CO(2), the
      percentage of parasitized erythrocytes (PPE) peaked at 10% in 24- and 6-well
      plates. It increased to 20-50% with the same culture medium but with 2.5% RBC in
      75 cm(2) flasks. Two clonal lines of Babesia sp. Xinjiang were screened using the
      limiting dilution method. Growth characteristics of these lines in vitro were
      measured by a microtiter-based spectrophotometric method and from the PPE. The
      generation time in sheep erythrocytes was between 15.20 h and 16.27 h.
      Furthermore, the host range of parasite was identified with in vitro culture and
      in vivo infection. Erythrocytes of sheep, cattle, sika deer and humans could be
      invaded into by lines in vitro, but the parasites could not propagate in human
      erythrocytes. The parasites could not enter erythrocytes from goats in vitro.
      However, in vivo, only sheep could be infected by lines. Finally, a Babesia sp.
      Xinjiang-like parasite (which shared 99.5% identity with the original strain of
      Babesia sp. Xinjiang) was isolated using this in vitro culture system from 1 of
      19 sheep blood samples collected from western Gansu province, China.

PMID- 22386949
TI  - Clinical negligence in ophthalmology: fifteen years of national health service
      litigation authority data.
AB  - OBJECTIVE: To categorize and understand the reasons behind ophthalmic clinical
      negligence claims in the National Health Service and how such claims can be
      avoided. DESIGN: Retrospective analyses of all ophthalmic clinical negligence
      claims between 1995 and 2009 were carried out. Data were obtained from the
      National Health Service Litigation Authority through the Freedom of Information
      Act. Claims were classified according to ophthalmic subspecialty, mean payment
      per subspecialty, severity, paid-to-closed ratio, and cost. PARTICIPANTS: One
      thousand two hundred fifty-three ophthalmology-related claims occurring from 1995
      through 2009. Of these, 963 claims were closed over the 15-year period. Eighty
      four were excluded because of insufficient case data. INTERVENTION: Retrospective
      analysis of all public sector ophthalmology litigation claims over a 15-year
      period in England. MAIN OUTCOME MEASURES: Subspecialty pertaining to claim, mean
      payment per claim, and severity of outcome of clinical incident. RESULTS: Nine
      hundred sixty-three claims were closed over a 15-year period, of which 67%
      resulted in payment. The total cost of claims was L32.1 million ($50.3 million),
      with a mean payment per claim of L33 300 ($52 300). The specialties with the
      highest mean payment per claim were neuro-ophthalmology and pediatric
      ophthalmology. Cataract subspecialty had the highest number of claims, accounting
      for 34% of all claims. CONCLUSIONS: Overall, the number of litigation claims in
      ophthalmology is low, relative to the high volume of outpatient and surgical
      workload.

PMID- 22386951
TI  - Differential outcome of infection with attenuated Salmonella in MyD88-deficient
      mice is dependent on the route of administration.
AB  - Activation of the innate immune system is a prerequisite for the induction of
      adaptive immunity to both infectious and non-infectious agents. TLRs are key
      components of the innate immune recognition system and detect pathogen-associated
      molecular patterns. Most TLRs utilize the MyD88 adaptor for their signaling
      pathways. In the current study, we investigated innate and adaptive immune
      responses to primary as well as secondary Salmonella infections in MyD88
      deficient (MyD88(-/-)) mice. Using i.p. or oral route of inoculation, we
      demonstrate that MyD88(-/-) mice are hypersusceptible to infection by an
      attenuated, double auxotrophic, mutant of Salmonella enterica serovar Typhimurium
      (S. typhimurium). This is manifested by 2-3 logs higher bacterial loads in target
      organs, delayed recruitment of phagocytic cells, and defective production of
      proinflammatory cytokines in MyD88(-/-) mice. Despite these deficiencies, MyD88(
      /-) mice developed Salmonella-specific memory Th1 responses and produced elevated
      serum levels of anti-Salmonella Abs, not only of Th1-driven (IgG2c, IgG3) but
      also IgG1 and IgG2b isotypes. Curiously, these adaptive responses were
      insufficient to afford full protection against a secondary challenge with a
      virulent strain of S. typhimurium. In comparison with the high degree of
      mortality seen in MyD88(-/-) mice following i.p. inoculation, oral infections led
      to the establishment of a state of long-term persistence, characterized by
      continuous bacterial shedding in animal feces that lasted for more than 6 months,
      but absence from systemic organs. These findings suggest that the absent
      expression of MyD88 affects primarily the innate effector arm of the immune
      system and highlights its critical role in anti-bacterial defense.

PMID- 22386950
TI  - Real-world assessment of physical activity in glaucoma using an accelerometer.
AB  - OBJECTIVE: To determine the association between glaucomatous visual field (VF)
      loss and the amount of physical activity and walking in normal life. DESIGN:
      Prospective, observational study. PARTICIPANTS: Glaucoma suspects without
      significant VF or visual acuity loss (controls) and glaucoma subjects with
      bilateral VF loss between 60 and 80 years of age. METHODS: Participants wore an
      accelerometer over 7 days of normal activity. MAIN OUTCOME MEASURES: Daily
      minutes of moderate or vigorous physical activity (MVPA) was the primary measure.
      Steps per day was a secondary measure. RESULTS: Fifty-eight controls and 83
      glaucoma subjects provided sufficient study days for analysis. Control and
      glaucoma subjects were similar in age, race, gender, employment status, cognitive
      ability, and comorbid illness (P>0.1 for all). Better-eye VF mean deviation (MD)
      averaged 0.0 decibels (dB) in controls and -11.1 dB in glaucoma subjects. The
      median control subject engaged in 16.1 minutes of MVPA daily and walked 5891
      steps/day, as compared with 12.9 minutes of MVPA daily (P = 0.25) and 5004
      steps/day (P = 0.05) for the median glaucoma subject. In multivariate models,
      glaucoma was associated with 21% less MVPA (95% confidence interval [CI], -53% to
      32%; P = 0.37) and 12% fewer steps per day (95% CI, -22% to 9%; P = 0.21) than
      controls, although differences were not statistically significant. There was a
      significant dose response relating VF loss to decreased activity, with each 5 dB
      decrement in the better-eye VF associated with 17% less MVPA (95% CI, -30% to 
      2%; P = 0.03) and 10% fewer steps per day (95% CI, -16% to -5%; P = 0.001).
      Glaucoma subjects in the most severe tertile of VF damage (better-eye VF MD worse
      than -13.5 dB) engaged in 66% less MVPA than controls (95% CI, -82% to -37%; P =
      0.001) and took 31% fewer steps per day (95% CI, -44% to -15%; P = 0.001). Other
      significant predictors of decreased physical activity included older age,
      comorbid illness, depressive symptoms, and higher body mass index. CONCLUSIONS:
      Overall, no significant difference in physical activity was found between
      individuals with and without glaucoma, although substantial reductions in
      physical activity and walking were noted with greater levels of VF loss. Further
      study is needed to characterize better the relationship between glaucoma and
      physical activity. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 22386952
TI  - Evaluation of serum estrogen-DNA adducts as potential biomarkers for breast
      cancer risk.
AB  - This study was conducted to determine whether the ratio of estrogen-DNA adducts
      to their respective metabolites and conjugates in serum differed between women
      with early-onset breast cancer and those with average or high risk of developing
      breast cancer. Serum samples from women at average risk (n=63) or high risk
      (n=80) for breast cancer (using Gail model) and women newly diagnosed with early
      breast cancer (n=79) were analyzed using UPLC-MS/MS. Adduct ratios were
      statistically compared among the three groups, and the Area Under the Receiver
      Operating Characteristic Curve (AUC) was used to identify a diagnostic cut-off
      point. The median adduct ratio in the average-risk group was significantly lower
      than that of both the high-risk group and the breast cancer group (p
      values<0.0001), and provided good discrimination between those at average versus
      high risk of breast cancer (AUC=0.84, 95% CI 0.77-0.90). Sensitivity and
      specificity were maximized at an adduct ratio of 77. For women in the same age
      and BMI group, the odds of being at high risk for breast cancer was 8.03 (95% CI
      3.46-18.7) times higher for those with a ratio of at least 77 compared to those
      with a ratio less than 77. The likelihood of being at high risk for breast cancer
      was significantly increased for those with a high adduct ratio relative to those
      with a low adduct ratio. These findings suggest that estrogen-DNA adducts deserve
      further study as potential biomarkers for risk of developing breast cancer.

PMID- 22386953
TI  - Androgen receptor expression in human thyroid cancer tissues: a potential
      mechanism underlying the gender bias in the incidence of thyroid cancers.
AB  - Gender bias in the incidence of thyroid cancer is well known, however, the
      underlying mechanism is largely unknown. The current study determines variations
      in the molecular characteristics of thyroid cancers between men and women. Normal
      and cancerous thyroid tissues were collected from a total of 125 men and women
      who underwent surgical thyroidectomy. Testosterone levels in serum and thyroid
      cancer tissues were elevated in women while it decreased in men compared to
      respective control groups; whereas, ligand binding activity increased in men and
      decreased in women. Androgen receptor (AR) mRNA expression increased in a
      majority of men while it decreased in a majority of women except those with
      follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson's
      correlation analysis showed a positive correlation of AR mRNA with AR protein,
      CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of
      men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in
      papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma
      (FTA), whereas AR mRNA showed a positive correlation with p53. Our study
      identified for the first time that AR is posttranscriptionally regulated by miR
      124a in thyroid cancer tissues. Further, our in vitro studies with a PTC cell
      line (NPA-87-1) showed miR-124a as the potent inhibitor of AR that impairs cell
      proliferation even in the presence of testosterone. Thus, the current study
      suggests that: (i) the varying pattern of testosterone level and AR status in
      thyroid tissues of men and women may predispose to the gender specific incidence
      of thyroid tumors and (ii) miR-124a plays a significant role in determining the
      AR gene expression pattern and thus, androgen mediated thyroid tumor growth.

PMID- 22386954
TI  - Mesothelin levels in urine are affected by glomerular leakage and tubular
      reabsorption.
AB  - BACKGROUND: Mesothelin is a soluble biomarker of malignant mesothelioma. Levels
      in serum, however, are also influenced by other factors, including age and
      glomerular filtration rate (GFR). The measurement of mesothelin in urine has
      recently gained interest, but the renal handling of this protein has not been
      sufficiently examined. PATIENTS AND METHODS: A total of 75 patients with benign
      kidney disease were prospectively included in the study. Mesothelin levels were
      measured in the serum and in the urine of all the participants by using enzyme
      linked immunosorbent assay. Urinary albumin and alpha 1-microglobulin (A1M)
      levels, which are markers of glomerular leakage and of decreased tubular
      reabsorption, respectively, and the estimated GFR (eGFR) of each participant were
      obtained. All urine analyte levels were standardized (std) against urinary
      creatinine levels. RESULTS: Absolute mesothelin levels in urine (median, 0.58
      nmol/L; interquartile range [IQR], 0.25-1.03 nmol/L) were significantly lower
      than those in serum (median, 1.74 nmol/L; IQR, 1.35-2.43 nmol/L; P < .001).
      Urinary mesothelin(std) levels positively correlated with serum mesothelin (r =
      0.35, P < .01), albumin(std) (r = 0.51, P < .001), and A1M(std) levels (r = 0.71,
      P < .001). Neither age nor eGFR were associated with urinary mesothelin(std)
      levels. Similarly, multiple linear regression analysis indicated that only
      albumin(std) and A1M(std) levels were significantly positively associated with
      the urinary mesothelin(std) levels (adjusted R(2) = 0.49). CONCLUSION: Mesothelin
      levels in urine are affected by impaired glomerular and tubular function, which
      can influence the interpretation of mesothelin measurements and might cause false
      positive results. These effects need to be accounted for to improve the further
      validation and possible clinical use of urinary mesothelin.

PMID- 22386955
TI  - Procalcitonin measurement for detection of serious bacterial infection in febrile
      children: comparison between two automated immunoassays.
AB  - OBJECTIVES: To assess the concordance of procalcitonin values at 3 cut-off ranges
      in a cohort of pediatric samples presenting with fever without source, using two
      different automated immunoassays. DESIGN AND METHODS: 65 frozen samples from
      children presenting with fever without source were thawed, tested on both Kryptor
      and VIDAS systems, and compared using a regression analysis, a Bland-Altman
      difference plot, and analysis of concordance at the clinically relevant cut-off
      points. RESULTS: Kryptor and VIDAS PCT results correlated remarkably well
      (r=0.952), with no significant difference in the frequency distribution over the
      3 cut-off ranges (p=0.1384). The strength of the agreement was good (kappa=0.759)
      with an overall concordance of 84.6%. CONCLUSION: Correlation and concordance of
      PCT values measured by both systems were good. This finding allows clinical
      implementation of both techniques with the same nominal PCT cut-off values for
      detection of serious bacterial infection in children presenting with fever
      without source.

PMID- 22386956
TI  - Pierre Youinou: life contribution to autoimmunity.

PMID- 22386957
TI  - Postoperative infection treatment score for the spine (PITSS): construction and
      validation of a predictive model to define need for single versus multiple
      irrigation and debridement for spinal surgical site infection.
AB  - BACKGROUND CONTEXT: There is very little evidence to guide treatment of patients
      with spinal surgical site infection (SSI) who require irrigation and debridement
      (I&D) in deciding need for single or multiple I&Ds or more complex wound
      management such as vacuum-assisted closure dressing or soft-tissue flaps.
      PURPOSE: The purpose of this study was to build a predictive model that
      stratifies patients with spinal SSI, allowing us to determine which patients will
      need single versus multiple I&D. The model will be validated and will serve as
      evidence to support a scoring system to guide treatment. STUDY DESIGN: A
      consecutive series of 128 patients from a tertiary spine center (collected from
      1999 to 2005) who required I&D for spinal SSI were studied based on data from a
      prospectively collected outcomes database. METHODS: More than 30 variables were
      identified by extensive literature review as possible risk factors for SSI and
      tested as possible predictors of risk for multiple I&D. Logistic regression was
      conducted to assess each variable's predictability by a "bootstrap" statistical
      method. A prediction model was built in which single or multiple I&D was treated
      as the "response" and risk factors as "predictors." Next, a second series of 34
      different patients meeting the same criteria as the first population were
      studied. External validation of the predictive model was performed by applying
      the model to the second data set, and predicted probabilities were generated for
      each patient. Receiver operating characteristic curves were constructed, and the
      area under the curve (AUC) was calculated. RESULTS: Twenty-four of one hundred
      twenty-eight patients with spinal SSI required multiple I&D. Six predictors:
      anatomical location, medical comorbidities, specific microbiology of the SSI, the
      presence of distant site infection (ie, urinary tract infection or bacteremia),
      the presence of instrumentation, and the bone graft type proved to be the most
      reliable predictors of need for multiple I&D. Internal validation of the
      predictive model yielded an AUC of 0.84. External validation analysis yielded AUC
      of 0.70 and 95% confidence interval of 0.51 to 0.89. By setting a probability
      cutoff of .24, the negative predictive value (NPV) for multiple I&D was 0.77 and
      positive predictive value (PPV) was 0.57. A probability cutoff of .53 yielded a
      PPV of 0.85 and NPV of 0.46. CONCLUSIONS: Patients with positive methicillin
      resistant Staphylococcus aureus culture or those with distant site infection such
      as bacteremia were strong predictors of need for multiple I&D. Presence of
      instrumentation, location of surgery in the posterior lumbar spine, and use of
      nonautograft bone graft material predicted multiple I&D. Diabetes also proved to
      be the most significant medical comorbidity for multiple I&D. The validation of
      this predictive model revealed excellent PPV and good NPV with appropriately
      chosen probability cutoff points. This study forms the basis for an evidence
      based classification system, the Postoperative Infection Treatment Score for the
      Spine that stratifies patients who require surgery for SSI, based on specific
      spine, patient, infection, and surgical factors to assess a low, indeterminate,
      and high risk for the need for multiple I&D.

PMID- 22386958
TI  - Accuracy and complications associated with posterior C1 screw fixation
      techniques: a radiographic and clinical assessment.
AB  - BACKGROUND CONTEXT: The variable C1 anatomy can make instrumentation challenging
      and prone to potentially severe complications. New techniques have expanded
      available options. PURPOSE: The aims of this study were to evaluate a large
      series of posterior C1 screws to determine accuracy by computed tomography (CT)
      scan; assess dimensions of "safe bony windows" with CT; and assess perioperative
      complication rate related to errant screw placement. STUDY DESIGN: Retrospective
      review of a single tertiary care spine database to identify patients with C1
      instrumentation between December 2002 and September 2008. PATIENT SAMPLE: The
      sample comprised 176 patients with 344 C1 screws. All 176 patients were assessed
      for perioperative complications related to their C1 screws. Twenty-nine patients
      did not have postoperative CT scans, leaving 147 patients with 286 screws for
      analysis of screw accuracy. OUTCOME MEASURES: The outcome measures consisted of a
      radiographic assessment of accuracy of placement of C1 instrumentation and a
      clinical assessment of perioperative complications related to C1 instrumentation
      focusing on neurologic and vascular injuries. METHODS: Clinical data were
      obtained from the medical record. Radiographic analyses included preoperative and
      postoperative CT scans to quantify the patients' bone and classify accuracy of
      instrumentation. Screws were graded using the following definitions: Type I,
      screw threads completely within the bone; Type II, less than half the diameter of
      the screw violates the surrounding cortex; and Type III, clear violation of
      transverse foramen or spinal canal. RESULTS: One hundred seventy-six patients (97
      males and 79 females) underwent posterior C1 screw (lateral mass [LM] or
      transarticular [TA]) fixation. A total of 344 screws were placed with 216 LM
      screws and 128 TA screws. Twenty-nine patients (58 screws) did not have
      postoperative CT scans and were not included for analysis of radiographic
      accuracy but were included in assessment of complications based on medical
      records. Ninety-six percent of screws (Type I or II) were rated as "safe," and
      86% of screws were rated as being ideal (Type I). Twelve screws (4%) were
      unacceptably placed (Type III). There were no known neurologic or vertebral
      artery injuries. One patient underwent revision surgery for a medially placed
      screw. Mean C1 LM width was 10.5 mm across all patients. Estimated blood loss
      averaged 331 mL. CONCLUSIONS: Our findings demonstrate a low incidence of
      complications associated with posterior screw instrumentation of the C1 LM.

PMID- 22386959
TI  - Effect of coronary bypass and valve structure on outcome in isolated valve
      replacement for aortic stenosis.
AB  - Reports differ regarding the effect of concomitant coronary artery bypass
      grafting (CABG) in patients who undergo aortic valve replacement (AVR) for aortic
      stenosis (AS), and no reports have described the effect of aortic valve structure
      in patients who undergo AVR for AS. A total of 871 patients aged 24 to 94 years
      (mean 70) whose AVR for AS was their first cardiac operation, with or without
      first concomitant CABG, were included. Patients who underwent mitral valve
      procedures were excluded. In comparison with the 443 patients (51%) who did not
      undergo CABG, the 428 (49%) who underwent concomitant CABG were significantly
      older, were more often male, had lower transvalvular peak systolic pressure
      gradients and larger valve areas, had lower frequencies of congenitally malformed
      aortic valves, had lighter valves by weight, had higher frequencies of systemic
      hypertension, and had longer stays in the hospital after AVR. Early and late (to
      10 years) mortality were similar by propensity-adjusted analysis in patients who
      did and did not undergo concomitant CABG. Congenitally unicuspid or bicuspid
      valves occurred in approximately 90% of those aged 21 to 50, in nearly 70% in
      those aged 51 to 70 years, and in just over 30% in those aged 71 to 95 years.
      Unadjusted and adjusted survival was significantly higher in patients with
      unicuspid or bicuspid valves compared to those with tricuspid valves. In
      conclusion, although concomitant CABG had no effect on the adjusted probability
      of survival, the type of aortic valve (unicuspid or bicuspid vs tricuspid)
      significantly affected the unadjusted and adjusted probability of survival.

PMID- 22386960
TI  - Candidatus "Thiodictyon syntrophicum", sp. nov., a new purple sulfur bacterium
      isolated from the chemocline of Lake Cadagno forming aggregates and specific
      associations with Desulfocapsa sp.
AB  - Strain Cad16(T) is a small-celled purple sulfur bacterium (PSB) isolated from the
      chemocline of crenogenic meromictic Lake Cadagno, Switzerland. Long term in situ
      observations showed that Cad16(T) regularly grows in very compact clumps of cells
      in association with bacteria belonging to the genus Desulfocapsa in a cell-to
      cell three dimensional structure. Previously assigned to the genus Lamprocystis,
      Cad16(T), was here reclassified and assigned to the genus Thiodictyon. Based on
      comparative 16S rRNA gene sequences analysis, isolate Cad16(T) was closely
      related to Thiodictyon bacillosum DSM234(T) and Thiodictyon elegans DSM232(T)
      with sequence similarities of 99.2% and 98.9%, respectively. Moreover, matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS) analysis separated Cad16(T) from other PSB genera, Lamprocystis and
      Thiocystis. Major differences in cell morphology (oval-sphere compared to rod
      shaped) and arrangement (no netlike cell aggregates), carotenoid group (presence
      of okenone instead of rhodopinal), chemolithotrophic growth as well as the
      ability to form syntrophic associations with a sulfate-reducing bacteria of the
      genus Desulfocapsa suggested a different species within the genus Thiodictyon.
      This isolate is therefore proposed and described as Candidatus "Thiodictyon
      syntrophicum" sp. nov., a provisionally novel species within the genus
      Thiodictyon.

PMID- 22386961
TI  - Relaxin augments the inflammatory IL6 response in the choriodecidua.
AB  - Intrauterine infection frequently leads to preterm birth (PTB), with the
      pathophysiology involving activation of the innate immune system and its
      associated inflammatory response. The choriodecidua produces relaxin (RLN) and
      elevated levels are associated with preterm premature rupture of the fetal
      membranes. However, it is not increased in bacterially-mediated PTB, but may act
      as an endogenous sterile inflammatory mediator. Elevated systemic RLN levels from
      the corpus luteum are also associated with PTB, but the mechanism is unknown. In
      clinical obstetrics, intrauterine inflammation or infection can coexist with
      elevated RLN. Therefore, in this study, we further characterized the effects of
      RLN alone or together with an inflammatory mediator on the production of IL1B,
      CSF2 (GM-CSF), IL6, IL8 and TNF, from chorionic cytotrophoblasts (CyT), decidual
      fibroblasts (DF) and stromal cells (DSC), using interleukin-1 beta (IL1B) to
      mimic sterile inflammation or lipopolysaccharide (LPS) for bacterial infection.
      Endogenous differences between the cells showed that the CyT expressed more RLN,
      its receptor RXFP1 and the RXFP1 splice variant D. CyT also showed the most
      robust cAMP response to RLN with increased IL6 secreted after 4 h, preceded by
      increased transcription at 1 h, likely due to activation of RXFP1 and cAMP. When
      all cell types were treated with IL1B and RLN, RLN augmented secretion of IL6 and
      IL8 from CyT and DF, but not DSC. Similarly, RLN augmented LPS-induced IL6
      secretion from CyT and DF. Despite the structural similarity between TLR4 and
      RXFP1, blocking TLR4 in CyT had no effect on RLN-induced IL6 secretion,
      suggesting specific activation of RXFP1. Thus, we have shown that in the presence
      of a low level of intrauterine inflammation/infection, elevated RLN could act on
      the CyT and DF to augment the inflammatory response, contributing to the
      pathophysiology of PTB. SUMMARY: RLN augments the inflammatory responses induced
      by IL1B or LPS in chorionic cytotrophoblasts and decidual fibroblasts.

PMID- 22386962
TI  - Placental expression of VEGF family mRNA in adverse pregnancy outcomes.
AB  - INTRODUCTION: The pregnancy complications preeclampsia, gestational hypertension,
      small for gestational age infants (SGA) and pre-term birth (PTB) affect
      approximately 21% of all pregnancies. The Vascular Endothelial Growth Factor
      family (VEGF) is implicated in the pathogenesis of these complications. We aimed
      to evaluate the placental mRNA expression of VEGFA, PGF, FLT1 and KDR in
      pregnancies complicated by preeclampsia, gestational hypertension, SGA infants
      and pre-term birth. METHOD: Placentae were collected at delivery from women with
      pregnancies complicated by preeclampsia (n = 18), gestational hypertension (n =
      15), normotensive SGA infants (n = 13), late spontaneous pre-term birth (n = 10)
      and uncomplicated pregnancy (n = 30). RNA was extracted and VEGFA, PGF, FLT1 and
      KDR expression were quantified using qRT-PCR. Kruskal Wallis test was used to
      compare placental mRNA expression in the adverse pregnancy outcome groups
      compared to uncomplicated term pregnancy. RESULTS: Compared to placental mRNA
      from uncomplicated pregnancies, VEGFA (p = 0.006), PGF (p < 0.001), KDR (p <
      0.001) and FLT1 (p = 0.02) mRNA were reduced in preeclamptic placentae; VEGFA (p
      < 0.001), PGF (p = 0.01) and KDR (p = 0.008) mRNA were reduced in placentae from
      pregnancies complicated by gestational hypertension; VEGFA (p = 0.03) mRNA was
      reduced in normotensive SGA pregnancies; VEGFA (p = 0.008), PGF (p = 0.01), KDR
      (p = 0.04) and FLT1 (p = 0.02) mRNA were reduced in placentae from late PTB.
      CONCLUSION: VEGF family of angiogenic growth factor mRNA expression in the
      placenta is reduced in gestational hypertensive disorders, SGA and in pre-term
      birth.

PMID- 22386963
TI  - WITHDRAWN: Quantitative analysis of solid binary mixtures-Vibrational
      spectroscopy of beta-lactam antibiotics within THz-region.
AB  - This article has been withdrawn at the request of the 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- 22386964
TI  - Morphine administration and abrupt cessation alter the behavioral diurnal
      activity pattern.
AB  - In mammals, there is an underlying mechanism that dictates the organism's
      biological functions and daily activity schedule, known as circadian rhythms,
      which play a major role in maintaining steady metabolism, homeostasis, and
      immunity. Limited research has been done investigating the effects of continuous
      opiate administration on the circadian rhythm activity pattern. A change in
      circadian activity pattern is suggested as an experimental model to demonstrate
      long-term effect of the drug. The objective of this study was to investigate the
      effects of morphine treatment on the long term activity (24 h) of the animal as
      well as the activity after abrupt removal, since prescribed medication containing
      morphine is widely used and abused and its long term effects are not known. Male
      Sprague-Dawley rats were contained in stable conditions with a standard
      light/dark cycle recordings taken before, during and after morphine pellet
      implantation. Cosinor analysis was used to fit a 24-hour curve to the activity
      pattern. Results indicate that morphine pellet administration alters the mesor,
      amplitude, the day-time and night-time activity levels, and demonstrates a
      remarkable change in the maximal circadian rhythm timing during the withdrawal
      period. The question whether morphine changes the circadian rhythm or a change in
      circadian rhythm results in tolerance and withdrawal is discussed.

PMID- 22386965
TI  - Usefulness of ultrasonography for gout.
AB  - Gout is a common arthritis caused by deposition of monosodium urate (MSU)
      crystals within joints secondary to chronic hyperuricemia. Joint damage can occur
      during evolution of the disease. The identification of MSU crystals in synovial
      fluid is the gold standard to diagnose gout. However, the diagnosis is sometimes
      difficult to do, particularly in atypical clinical presentations or when small
      joints are involved. Radiography is often normal at the early stage of gout. MRI
      and CT-scan are costly and availability of these imaging techniques may be
      problematic in clinical practice. Ultrasonography (US) appears useful for
      diagnosis and management of the disease. Several ultrasound features evocating
      gout have been described with different sensitivity and specificity. We reviewed
      the literature for evidence of the ability and usefulness of US for diagnosis of
      early-stage and established gout.

PMID- 22386966
TI  - Cigarette smoking and white matter microstructure in schizophrenia.
AB  - The majority of patients with schizophrenia smoke cigarettes. Both nicotine use
      and schizophrenia have been associated with alterations in brain white matter
      microstructure as measured by diffusion tensor imaging (DTI). The purpose of this
      study was to examine fractional anisotropy (FA) in smoking and non-smoking
      patients with schizophrenia and in healthy volunteers. A total of 43 patients (28
      smoking and 15 non-smoking) with schizophrenia and 40 healthy, non-smoking
      participants underwent DTI. Mean FA was calculated in four global regions of
      interest (ROIs) (whole brain, cerebellum, brainstem, and total cortical) as well
      as in four regional ROIs (frontal, temporal, parietal and occipital lobes). The
      non-smoking patient group had a significantly higher intellectual quotient (IQ)
      compared with the patients who smoked, and our results varied according to
      whether IQ was included as a covariate. Without IQ correction, significant
      between-group effects for FA were found in four ROIs: total brain, total
      cortical, frontal lobe and the occipital lobe. In all cases the FA was lower
      among the smoking patient group, and highest in the control group. Smoking
      patients differed significantly from non-smoking patients in the frontal lobe
      ROI. However, these differences were no longer significant after IQ correction.
      FA differences between non-smoking patients and controls were not significant.
      Among smoking and non-smoking patients with schizophrenia but not healthy
      controls, FA was correlated with IQ. In conclusion, group effects of smoking on
      FA in schizophrenia might be mediated by IQ. Further, low FA in specific brain
      areas may be a neural marker for complex pathophysiology and risk for diverse
      problems such as schizophrenia, low IQ, and nicotine addiction.

PMID- 22386967
TI  - Parental substance abuse and function of the motivation and behavioral inhibition
      systems in drug-naive youth.
AB  - It is hypothesized that the development of substance abuse (SA) may be due to
      imbalance in functions of the motivation-reward and behavioral inhibition systems
      in the brain. This speaks to the search for biological risk factors for SA in
      drug-naive children who also exhibit motivational and inhibitory control
      deficits; however, this type of research is currently lacking. The objective of
      this study was to establish a neurobiological basis for addiction vulnerability
      using functional magnetic resonance imaging (fMRI) in drug-naive youth with
      attention deficit/hyperactivity disorder (ADHD). We hypothesized that children
      with ADHD alone would show higher activity in regions of the motivation-reward
      and behavioral inhibition systems than children with ADHD and a parental history
      of SA. Toward this goal we scanned 20 drug-naive children with ADHD ages 8-13
      while performing an event-related reward task. High (N=10) and low (N=10) risk
      subjects were identified, based on parental history of SA. The effects of
      anticipation, conflict, and reward were assessed with appropriate linear
      contrasts, and between-group differences were assessed using statistical
      parametric mapping. The two groups did not differ on behavioral measures of the
      task. The fMRI results show heightened activation in the brain motivational
      reward system and reduced activation of the inhibitory control system in high
      risk compared to low-risk children. These results suggest that a functional
      mismatch between these two systems may represent one possible biological
      underpinning of SA risk, which is conferred by a parental history of addiction.

PMID- 22386968
TI  - Structural deficits in the emotion circuit and cerebellum are associated with
      depression, anxiety and cognitive dysfunction in methadone maintenance patients:
      a voxel-based morphometric study.
AB  - Heroin users on methadone maintenance treatment (MMT) have elevated rates of co
      morbid depression and are associated with have higher relapse rates for substance
      abuse. Structural abnormalities in MMT patients have been reported, but their
      impact on clinical performance is unknown. We investigated differences in gray
      matter volume (GMV) between 27 MMT patients and 23 healthy controls with voxel
      based morphometry, and we correlated findings in the patients with Beck
      Depression Inventory scores, Beck Anxiety Inventory scores, and diminished
      cognitive functioning. MMT patients exhibited higher emotional deficits than
      healthy subjects. There was significantly smaller GMV in multiple cortices,
      especially in the left inferior frontal gyrus and left cerebellar vermis in the
      MMT group. The smaller GMV in the pre-frontal cortices, left sub-callosal
      cingulate gyrus, left post-central gyrus, left insula, and right cerebellar
      declive correlated with higher depression scores. The smaller GMV in the pre
      frontal cortices, left sub-callosal cingulate gyrus, and left postcentral gyrus
      also correlated with higher anxiety scores, while smaller GMV in the cerebellum
      and bilateral insula was associated with impaired performance on tests of
      executive function. These results reveal that MMT patients have low GMV in brain
      regions that are hypothesized to influence cognition and emotion, and the GMV
      findings might be involved comorbid disorders in the MMT group.

PMID- 22386969
TI  - Adults with attention-deficit/hyperactivity disorder - a diffusion-tensor imaging
      study of the corpus callosum.
AB  - The objective of the present study was to investigate the microstructure and the
      macrostructure of the corpus callosum (CC) in adults with Attention
      Deficit/Hyperactivity Disorder (ADHD) by means of magnetic resonance imaging
      (MRI). Twenty-nine participants with ADHD and 37 controls were included from the
      Norwegian ADHD project in Bergen. We measured the fractional anisotropy (FA)
      values, as well as the size of different subdivisions of the CC, using diffusion
      tensor imaging (DTI) and anatomical MRI. The isthmus/splenium part of the CC in
      the ADHD group showed reduced FA values compared to the control group, whereas
      the size of the CC did not differ across groups. Our findings thus demonstrate a
      divergence between microstructural and macrostructural measures in the CC of
      adults with ADHD. This contrasts with findings in children demonstrating callosal
      abnormalities in both microstructure and macrostructure. Our results may indicate
      that adults with ADHD in part have succeeded in passing by an earlier
      developmental delay of the CC, resulting in a normalization of callosal
      macrostructure into adulthood. However, microstructural differences are still
      present in adults, which may point to an abnormal lateralization in adults with
      ADHD, or could be a sign of a persisting impairment.

PMID- 22386970
TI  - Autobiographical memory in depression: an fMRI study.
AB  - Depression is associated with three distinct alterations in memory functioning:
      mood-congruent recall, over-generality, and intrusive memories. These concern the
      autobiographical memory system, yet no previous studies have examined the neural
      correlates of autobiographical memory function in depression. In the present
      study we used functional magnetic resonance imaging (fMRI) to assess depressed
      and control participants during an autobiographical memory task. In their first
      visit to the laboratory, participants wrote a narrative account of a distressing
      event. Participants were scanned during the second visit while they viewed old
      items from their narrative and new words or phrases in a recognition memory task.
      Activity common to both groups during the successful identification of personal
      emotional memories was observed in regions previously associated with
      autobiographical memory retrieval. Reduced activity in the depressed group was
      observed in three regions of the prefrontal cortex associated with cognitive,
      emotional, and memory inhibition. These results are consistent with a failure by
      depressed individuals to inhibit task-irrelevant information during an
      autobiographical memory task.

PMID- 22386971
TI  - High b-value diffusion-weighted imaging: a sensitive method to reveal white
      matter differences in schizophrenia.
AB  - Over the last 10 years, diffusion-weighted imaging (DWI) has become an important
      tool to investigate white matter (WM) anomalies in schizophrenia. Despite
      technological improvement and the exponential use of this technique,
      discrepancies remain and little is known about optimal parameters to apply for
      diffusion weighting during image acquisition. Specifically, high b-value
      diffusion-weighted imaging known to be more sensitive to slow diffusion is not
      widely used, even though subtle myelin alterations as thought to happen in
      schizophrenia are likely to affect slow-diffusing protons. Schizophrenia patients
      and healthy controls were scanned with a high b-value (4000 s/mm(2)) protocol.
      Apparent diffusion coefficient (ADC) measures turned out to be very sensitive in
      detecting differences between schizophrenia patients and healthy volunteers even
      in a relatively small sample. We speculate that this is related to the
      sensitivity of high b-value imaging to the slow-diffusing compartment believed to
      reflect mainly the intra-axonal and myelin bound water pool. We also compared
      these results to a low b-value imaging experiment performed on the same
      population in the same scanning session. Even though the acquisition protocols
      are not strictly comparable, we noticed important differences in sensitivities in
      the favor of high b-value imaging, warranting further exploration.

PMID- 22386973
TI  - Developmental progress and creatine restoration upon long-term creatine
      supplementation of a patient with arginine:glycine amidinotransferase deficiency.
AB  - BACKGROUND: Arginine:glycineamidinotransferase (AGAT/GATM) deficiency has been
      described in 9 patients across 4 families. Here we describe the clinical outcome
      and response to creatine supplementation in a patient of the second family
      affected with AGAT deficiency-a 9-year-old girl. PATIENT AND METHODS: Delayed
      motor milestones were noticed from 4 months of age and at 14 months moderate
      hypotonia, developmental delay and failure to thrive. Laboratory studies revealed
      low plasma creatine as well as extremely low levels of guanidinoacetic acid in
      urine and plasma. Proton magnetic resonance spectroscopy (MRS) of the brain
      showed absence of creatine. DNA sequence analysis revealed a homozygous mutation
      (c.484+1G>T) in the AGAT/GATM gene. AGAT activity was not detectable in
      lymphoblasts and RNA analysis revealed a truncated mRNA (r.289_484del196) that is
      degraded via Nonsense Mediated Decay. At 16 months, Bayley's Infant Development
      Scale (BIDS) showed functioning at 43% of chronologic age. Oral creatine
      supplementation (up to 800 mg/kg/day) was begun. RESULTS: At age 9 years she
      demonstrated advanced academic performance. Partial recovery of cerebral creatine
      levels was demonstrated on MRS at 25 months of age. Brain MRS at 40 months of age
      revealed a creatine/NAA ratio of about 80% of that in age-matched controls.
      CONCLUSIONS: 8 years post initiation of oral creatine supplementation, patient
      demonstrates superior nonverbal and academic abilities, with average verbal
      skills. We emphasize that early diagnosis combined with early treatment onset of
      AGAT deficiency may lead to improvement of developmental outcome.

PMID- 22386972
TI  - Emphysema in an adult with galactosialidosis linked to a defect in primary
      elastic fiber assembly.
AB  - Galactosialidosis is a lysosomal storage disorder caused by loss of function of
      protective protein cathepsin A, which leads to secondary deficiencies of beta
      galactosidase and neuraminidase-1. Emphysema has not been previously reported as
      a possible complication of this disorder, but we now describe this condition in a
      41-year-old, non-smoking male. Our patient did not display deficiency in alpha-1
      antitrypsin, the most common cause of emphysema in non-smokers, which brings
      about disseminated elastolysis. We therefore hypothesized that loss of cathepsin
      A activity was responsible because of previously published evidence showing it is
      prerequisite for normal elastogenesis. We now present experimental evidence to
      support this theory by demonstrating impaired primary elastogenesis in cultures
      of dermal fibroblasts from our patient. The obtained data further endorse our
      previous finding that functional integrity of the cell surface-targeted molecular
      complex of cathepsin A, neuraminidase-1 and the elastin-binding protein (spliced
      variant of beta-galactosidase) is prerequisite for the normal assembly of elastic
      fibers. Importantly, we also found that elastic fiber production was increased
      after exposure either to losartan, spironolactone, or dexamethasone. Of immediate
      clinical relevance, our data suggest that surviving patients with
      galactosialidosis should have periodic assessment of their pulmonary function. We
      also encourage further experimental exploration of therapeutic potential of the
      afore-mentioned elastogenesis-stimulating drugs for the alleviation of
      pathological processes in galactosialidosis that could be mechanistically linked
      to impaired deposition of elastic fibers.

PMID- 22386974
TI  - Improving the preventive care of asplenic patients.

PMID- 22386975
TI  - CYP24 inhibition preserves 1alpha,25-dihydroxyvitamin D(3) anti-proliferative
      signaling in lung cancer cells.
AB  - Human lung tumors aberrantly express the 1alpha,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3))-catabolizing enzyme, CYP24. We hypothesized that CYP24 reduces
      1,25(OH)(2)D(3)-mediated transcription and allows lung cancer cells to escape its
      growth-inhibitory action. To test this, H292 lung cancer cells and the CYP24
      selective inhibitor CTA091 were utilized. In H292 cells, CTA091 reduces
      1,25(OH)(2)D(3) catabolism, significantly increases 1,25(OH)(2)D(3)-mediated
      growth inhibition, and increases 1,25(OH)(2)D(3) effects on induced and repressed
      genes in gene expression profiling studies. Pathway mapping of repressed genes
      uncovered cell cycle as a predominant 1,25(OH)(2)D(3) target. In H292 cells,
      1,25(OH)(2)D(3) significantly decreases cyclin E2 levels and induces G(0)/G(1)
      arrest. A broader set of cyclins is down-regulated when 1,25(OH)(2)D(3) is
      combined with CTA091, and cell cycle arrest further increases. Effects of CTA091
      on 1,25(OH)(2)D(3) signaling are vitamin D receptor-dependent. These data provide
      evidence that CYP24 limits 1,25(OH)(2)D(3) anti-proliferative signaling in cancer
      cells, and suggest that CTA091 may be beneficial in preserving 1,25(OH)(2)D(3)
      action in lung cancer.

PMID- 22386976
TI  - Bacteriology of infected burn wounds in the burn wards of a teaching hospital in
      Southwest Nigeria.
AB  - BACKGROUND: Burns are characterized by the loss of varying proportions of the
      protective layers of the skin, depression of immune responses, and increased
      wound susceptibility to infection. Wound infection is a major cause of morbidity
      and mortality in burn cases. This study characterizes those factors that
      predispose burn wounds to infection and the bacteriology of the microorganisms in
      our environment. PATIENTS AND METHODS: Prospective study of burns patients that
      were admitted and treated at the Lagos State University Teaching Hospital
      (LASUTH), Ikeja-Lagos, Nigeria between January 1 and May 31, 2010 was carried
      out. Information about the demographics, aetiology/mechanism of burns, interval
      between the time of injury and admission, microbial studies, and antibiotic
      therapy were collected and analyzed. RESULTS: A total of 74 patients consisting
      of 43 males and 31 females were seen. The ages range between one week and 95 +/-
      22.42 years. Wound infections were confirmed in 28 patients (infection rate of
      37.84 per 100 patients). Delayed presentation at LASUTH and length of hospital
      stay were significantly related to the development of wound infection.
      Pseudomonas aeruginosa and Proteus mirabilis were the most common infective
      organisms occurring in 53.6 and 10.7 percentages respectively. The isolated
      organisms were resistant to the beta-lactam antibiotics and mostly sensitive to
      carbapenem and aztreonam preparations. CONCLUSION: Factors predisposing to
      invasive wound infections in our environment were highlighted and suggestions
      made on methods that could reduce the infections and thus reduce morbidity and
      mortality in burns.

PMID- 22386977
TI  - Effect of whole body vibration on leg muscle strength after healed burns: a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of eight weeks whole body vibration
      training program on leg muscle strength (force-producing capacity) in adults
      after healed burns. DESIGN: Randomized controlled trial. SETTING: Faculty of
      Physical Therapy, Cairo University. SUBJECTS: Thirty-one burned patients
      participated in the study and were randomized into whole body vibration group and
      control group. Non-burned healthy adults were assessed similarly to burned
      subjects and served as matched healthy controls. METHODS: The whole body
      vibration group performed an eight weeks vibration program three times a week on
      a vibration platform; the control group received home based physical therapy
      program without vibration training. MAIN MEASURES: Assessment of knee extensors
      and ankle planter flexor strength by isokinetic dynamometer at 150 degrees /s
      were performed at the beginning of the study and at the end of the training
      period for both groups. RESULTS: Subjects with burns more than 36% TBSA produced
      significantly less torque in the quadriceps and calf muscle than non-burned
      healthy subjects. Patients in whole body vibration group showed a significant
      improvement in knee extensor and ankle planter flexor strength as compared with
      those in the control group. Knee extensor strength and percent improvement was
      233.40+/-5.74 (64.93+/-3.03 change score) and 38.54% for the vibration group and
      190.07+/-3.99 (21.66+/-4.41 change score) and 12.86% for the control group, ankle
      plantar flexor strength and percent improvement was 156.27+/-5.95 (54.53+/-6.16
      change score) and 53.70% for the vibration group and 116.13+/-3.24 (14.66+/-2.71
      change score) and 14.52% for the control group. CONCLUSIONS: Participation in
      whole body vibration program resulted in a greater improvement in quadriceps and
      calf muscle strength in adults with healed thermal burn compared to base line
      values; a WBV program is an effective for strength gain in rehabilitation of
      burned patients.

PMID- 22386978
TI  - C-C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3
      yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors.
AB  - A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were
      synthesized via AlCl(3)-mediated C-C bond forming reaction between 2
      chloroquinoline-3-carbonitrile and various indoles. The methodology does not
      require any N-protection of the indoles employed and provided the corresponding
      products in good yields. The molecular structure of a representative compound was
      established unambiguously by single crystal X-ray diffraction and structural
      elaboration of a compound synthesized has been demonstrated. Many of these
      compounds synthesized showed PDE4 inhibitory properties in vitro. A brief
      structure-activity relationship studies within the series along with docking
      results of a representative compound (EC(50) ~0.89 MUM) is presented.

PMID- 22386979
TI  - Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual
      agonists.
AB  - To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a
      series of gamma-lactam prostaglandin E analogs bearing a 16-phenyl omega-chain
      were synthesized and evaluated. Structural hybridization of 1 and 2, followed by
      more detailed chemical modification of the benzoic acid moiety, led us to the
      discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal
      compound in the series. An isomer of this compound, the 2-mercaptothiazole-5
      carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4
      receptor affinities, respectively. Structure activity relationship data from an
      in vitro mouse receptor binding assay are presented. Continued evaluation in an
      in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17,
      optimized for sustained compound release from PLGA microspheres, demonstrated its
      effectiveness in a rat bone fracture-healing model following topical
      administration.

PMID- 22386980
TI  - Mutation of active site residues Asn67 to Ile, Gln92 to Val and Leu204 to Ser in
      human carbonic anhydrase II: influences on the catalytic activity and affinity
      for inhibitors.
AB  - Site-directed mutagenesis has been used to change three amino acid residues
      involved in the binding of inhibitors (Asn67Ile; Gln92Val and Leu204Ser) within
      the active site of human carbonic anhydrase (CA, EC 4.2.1.1) II (hCA II).
      Residues 67, 92 and 204 were changed from hydrophobic to hydrophilic ones, and
      vice versa. The Asn67Ile and Leu204Ser mutants showed similar k(cat)/K(M) values
      compared to the wild type (wt) enzyme, whereas the Gln92Val mutant was around 30%
      less active as a catalyst for CO(2) hydration to bicarbonate compared to the wt
      protein. Affinity for sulfonamides/sulfamates was decreased in all three mutants
      compared to wt hCA II. The effect was stronger for the Asn67Ile mutant (the
      closest residue to the zinc ion), followed by the Gln92Val mutant (residue
      situated in the middle of the active site) and weakest for the Leu204Ser mutant,
      an amino acid situated far away from the catalytic metal ion, at the entrance of
      the cavity. This study shows that small perturbations within the active site
      architecture have influences on the catalytic efficiency but dramatically change
      affinity for inhibitors among the CA enzymes, especially when the mutated amino
      acid residues are nearby the catalytic metal ion.

PMID- 22386981
TI  - Synthesis and P2Y2 receptor agonist activities of uridine 5'-phosphonate
      analogues.
AB  - We explored the influence of modifications of uridine 5'-methylenephosphonate on
      biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a
      series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a
      suitably protected uridine 5'-aldehyde with
      [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a
      Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the
      P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar
      range. Although maximal activities observed with the phosphonate analogues were
      much less than observed with UTP, high concentrations of the phosphonates had no
      effect on the stimulatory effect of UTP. These results suggest that these
      phosphonates bind to an allosteric site of the P2Y(2) receptor.

PMID- 22386982
TI  - Perturbing pro-survival proteins using quinoxaline derivatives: a structure
      activity relationship study.
AB  - In HeLa cells the combinatorial knockdown of Bcl-xL and Mcl-1 is sufficient to
      induce spontaneous apoptosis. Quinoxaline derivatives were screened for the
      induction of Mcl-1 dependent apoptosis using a cell line without functional Bcl
      xL. Quinoxaline urea analog 1 h was able to specifically induce apoptosis in an
      Mcl-1 dependent manner. We demonstrate that even small changes to 1h results in
      dramatic loss of activity. In addition, 1 h and ABT-737 synergistically inhibit
      cell growth and induce apoptosis. Our results also suggest that 1h could have
      therapeutic potential against ABT-737 refractory cancer.

PMID- 22386983
TI  - Synthesis and evaluation of fluorobenzoylated di- and tripeptides as inhibitors
      of cyclooxygenase-2 (COX-2).
AB  - A series of fluorobenzoylated di- and tripeptides as potential leads for the
      development of molecular probes for imaging of COX-2 expression was prepared
      according to standard Fmoc-based solid-phase peptide synthesis. All peptides were
      assessed for their COX-2 inhibitory potency and selectivity profile in a
      fluorescence-based COX binding assay. Within the series of 15 peptides tested,
      cysteine-containing peptides numbered 7, 8, 11 and 12, respectively, were the
      most potent COX-2 inhibitors possessing IC(50) values ranging from 5 to 85 MUM.
      Fluorobenzoylated tripeptides 7 and 8 displayed some COX-2 selectivity (COX-2
      selectivity index 2.1 and 1.6), whereas fluorobenzoylated dipeptides 11 and 12
      were shown not to be COX-2 selective. Fluorbenzoylated tripeptide FB-Phe-Cys-Ser
      OH was further used in molecular modeling docking studies to determine the
      binding mode within the active site of the COX-2 enzyme.

PMID- 22386984
TI  - In silico scaffold evaluation and solid phase approach to identify new gelatinase
      inhibitors.
AB  - Among matrix metalloproteinases (MMPs), gelatinases MMP-2 (gelatinase A) and MMP
      9 (gelatinase B) play a key role in a number of physiological processes such as
      tissue repair and fibrosis. Many evidences point out their involvement in a
      series of pathological events, such as arthritis, multiple sclerosis,
      cardiovascular diseases, inflammatory processes and tumor progression by
      degradation of the extracellular matrix. To date, the identification of non
      specific MMP inhibitors has made difficult the selective targeting of
      gelatinases. In this work we report the identification, design and synthesis of
      new gelatinase inhibitors with appropriate drug-like properties and good profile
      in terms of affinity and selectivity. By a detailed in silico protocol and
      innovative and versatile solid phase approaches, a series of 4-thiazolydinyl-N
      hydroxycarboxyamide derivatives were identified. In particular, compounds 9a and
      10a showed a potent inhibitory activity against gelatinase B and good selectivity
      over the other MMP considered in this study. The identified compounds could
      represent novel potential candidates as therapeutic agents.

PMID- 22386985
TI  - The space of access to primary mental health care: a qualitative case study.
AB  - Guided by theoretical perspectives of relational social science, this paper draws
      on reanalyses of multiple qualitative datasets related to a multi-ethnic,
      economically disadvantaged area in Liverpool, UK, with the aim to advance general
      understanding of access to primary mental health care while using local Somali
      minority as an instrumental focus. The findings generate a novel concept: the
      space of access. The shape and dynamics of the space of access are determined by
      at least four fields of tensions: understandings of area and community; cognitive
      mapping of mental well-being, illness and care; positioning of primary care
      services; and dynamics of resources beyond the 'medical zone' of care. The
      conclusions indicate a need for de-centring and re-connecting the role of medical
      professionals within primary care which itself needs to be transformed by
      endorsement of multiple avenues of access to diverse support and intrepid
      communication among all involved actors.

PMID- 22386986
TI  - Characterization and mass balance of dioxin from a large-scale municipal solid
      waste incinerator in China.
AB  - The input and output samples from existing large-scale municipal solid waste
      incinerator (MSWI) were collected and analyzed for polychlorinated dibenzo-r
      dioxins and dibenzofurans (PCDD/Fs) in this study, aiming to evaluate PCDD/F
      characteristic and the corresponding mass balance through the whole system. The
      grate-type MSWI is equipped with semi-dry scrubber, activated carbon injection,
      and bag filter as air pollutant control devices (APCDs). Results showed that on
      the output side, the stack gas, bottom ash and fly ash presented their mean
      dioxin levels of 0.078 ng I-TEQ/Nm(3), 12.94 ng I-TEQ/kg and 858 ng I-TEQ/kg,
      respectively, and showed large similarities in congener profiles. Instead, on the
      input side, the municipal solid waste (MSW) presented a mean dioxin level of
      15.56 ng I-TEQ/kg and a remarkable difference in congener profiles compared with
      those of the output. The dioxin mass balance demonstrated that the annual dioxin
      input value was around 5.38 g I-TEQ/yr, lower than the total output value (7.62 g
      I-TEQ/yr), signifying a positive dioxin balance of about 2.25 g I-TEQ/yr.

PMID- 22386987
TI  - Influence of regulation on the productivity of waste utilities. What can we learn
      with the Portuguese experience?
AB  - This paper examines the merits and the perverse effects of quality of service
      regulation in the performance of urban waste services when implemented alone and
      compares the performance of different economic regulatory methods. By means of a
      productivity analysis, we investigate the influence of a five-year period of
      regulation on the performance of Portuguese urban waste utilities using an
      unbalanced panel data for the period 2001-2008. Different non-parametric methods
      were applied to estimate the productivity change, all leading to similar
      outcomes. We observed a tendency of productivity decline in the urban waste
      utilities and concluded that in spite of the unequivocal improvements in the
      quality of service induced by sunshine regulation, more should be done as far as
      economic regulation is concerned. We also found that the use of sunshine
      regulation together with low incentive economic regulatory methods is not
      positive, leading to overinvestment rather than to value for money.

PMID- 22386988
TI  - The impact of caring for those with chronic obstructive pulmonary disease (COPD)
      on carers' psychological well-being: a narrative review.
AB  - OBJECTIVE: To identify and summarise studies of the psychological well-being of
      informal carers of people with chronic obstructive pulmonary disease. DESIGN: The
      review included studies if they reported the carers perspective of caregiving -
      studies that focused mostly on the person with chronic obstructive pulmonary
      disease were included only if the carers perspective of the caregiver role could
      be extracted. DATA SOURCES: Electronic searches of MEDLINE, CINAHL, PsychInfo,
      Sociological Abstracts and The Cochrane Library were carried out between December
      2008 and February 2009, with update searches undertaken in June 2011. REVIEW
      METHODS: A narrative approach was adopted to evaluate studies according to their
      contribution and drew together evidence from a range of methodologies, including
      qualitative and quantitative studies. RESULTS: Twenty studies were included in
      this review. Twelve studies focuses only on the caregiver (quantitative studies=7
      and qualitative studies=5) and eight included caregivers and the person with
      chronic obstructive pulmonary disease (quantitative=6 and qualitative=2). Common
      methodological limitations of studies included in this review were a lack of non
      caregiver age-matched comparison groups, focus on the experience of female
      carers, small sample sizes, and failure to follow-up caregivers longitudinally.
      Seven studies provided estimates of the prevalence of psychological distress
      among caregivers but no conclusions could be drawn from the current evidence
      base. The totality of the current evidence-base suggests that many factors are
      related to caregiver psychological distress, but it is not possible to gauge the
      prevalence of this at present. CONCLUSION: Further studies are needed to clarify
      the prevalence of chronic obstructive pulmonary disease caregivers' psychological
      comorbidity and disease specific factors that predict poorer carer health
      outcomes. That work will enable appropriate interventions to be developed and
      evaluated.

PMID- 22386989
TI  - A qualitative study of the work environments of Mexican nurses.
AB  - BACKGROUND: Studies of the nursing work environment are increasingly common in
      developed countries, but few exist in developing countries. Because of resource
      differences between the two contexts, researchers need to clarify what aspects of
      the work environments are similar and different. OBJECTIVES: To study the
      perspectives of Mexican nurses about their work environments to determine
      similarities and differences to results from developed world studies. DESIGN: A
      secondary, directed content analysis of qualitative data from 46 Spanish language
      interviews using workplace-oriented themes. SETTING: Purposively selected Mexican
      states from four regions of the country that reflect the country's socioeconomic
      differences. PARTICIPANTS: Practicing Mexican nurses with at least 1 year of
      clinical experience and currently working in nursing. Participants were recruited
      through convenience and snowball sampling techniques. METHODS: Initial data
      collection occurred in 2006 and 2008 during a broader study about
      professionalization processes that occurred in Mexican nursing between 1980 and
      2005. The secondary, directed content analysis focused on an in-depth exploration
      of a central theme that emerged from the two original studies: the workplace. The
      directed content analysis used themes from the global nursing work environment
      literature to structure the analysis: professional relationships, organizational
      administrative practices, and quality of care and services. RESULTS: The three
      themes from the global literature were relevant for the Mexican context and a new
      one emerged related to hiring practices. By category, the same factors that
      created positive or negative perceptions of the work environment matched findings
      from other international studies conducted in developed countries. The
      descriptors of the category, however, had different conceptual meanings that
      illustrate the health system challenges in Mexico. CONCLUSIONS: Findings from
      this study suggest that studies that seek to measure nursing work environments
      will most likely apply in Mexico and other Latin American or middle-income
      countries. Instruments designed to measure the work environment of nurses in
      these countries may prove relevant in those contexts, but require careful
      adaptation and systematic translations to ensure it.

PMID- 22386990
TI  - CD45-mediated signaling pathway is involved in Rhizoctonia bataticola lectin
      (RBL)-induced proliferation and Th1/Th2 cytokine secretion in human PBMC.
AB  - We earlier reported the mitogenic and immunostimulatory activities of Rhizoctonia
      bataticola lectin (RBL), purified from phytopathogenic fungus R. bataticola in
      human PBMC. The lectin demonstrates specificity towards glycoproteins containing
      complex N-glycans. Since CD45-protein tyrosine phosphatase that abundantly
      expresses N-glycans is important in T-cell signaling, the study aimed to
      investigate the involvement of CD45 in the immunomodulatory activities of RBL.
      Flowcytometry and confocal microscopy studies revealed that RBL exhibited binding
      to PBMC and colocalized with CD45. The binding was comparable in cells expressing
      different CD45 isoforms-RA, -RB and -RO. CD45 blocking antibody reduced the
      binding and proliferation of PBMC induced by RBL. CD45-PTPase inhibitor
      dephostatin inhibited RBL-induced proliferation, expression of CD25 and pZAP-70.
      RBL-induced secretion of Th1/Th2 cytokines were significantly inhibited in
      presence of dephostatin. Also, dephostatin blocked phosphorylation of p38MAPK and
      STAT-5 that was crucial for the biological functions of RBL. The study
      demonstrates the involvement of CD45-mediated signaling in RBL-induced PBMC
      proliferation and Th1/Th2 cytokine secretion through activation of p38MAPK and
      STAT-5.

PMID- 22386992
TI  - L-Tryptophan prevents Escherichia coli biofilm formation and triggers biofilm
      degradation.
AB  - The effect of deletion of trp operon and tna operon on the Escherichia coli
      biofilm formation was investigated in order to elucidate the role of L-tryptophan
      metabolism in biofilm formation. trp operon deletion mutants DeltatrpC, DeltatrpD
      and DeltatrpE deficient in L-tryptophan biosynthesis showed higher biofilm
      formation. In addition, DeltatnaC with increased L-tryptophan degradation
      activity showed higher biofilm formation. On the contrary, DeltatnaA deletion
      mutant which lost L-tryptophan degradation activity showed low biofilm formation.
      From these results, it was suggested that decrease of intracellular L-tryptophan
      level induced biofilm formation and increase of L-tryptophan repressed biofilm
      formation. So the effect of the addition of L-tryptophan to the medium on the E.
      coli biofilm formation was investigated. L-Tryptophan addition at starting
      culture decreased biofilm formation and furthermore L-tryptophan addition after
      16 h culture induced the degradation of preformed biofilm. From the above
      results, it was suggested that maintenance of high intracellular L-tryptophan
      concentration prevents E. coli biofilm formation and elevation of intracellular L
      tryptophan concentration triggers degradation of matured biofilm.

PMID- 22386991
TI  - Identification of a thrombin cleavage site and a short form of ADAMTS-18.
AB  - We previously reported that C-terminal fragment of ADAMTS-18 induces platelet
      fragmentation through ROS release. We have shown that thrombin cleaves ADAMTS-18
      and that a short form of ADAMTS-18 in in vitro translational assay. However, the
      exact thrombin cleavage site and whether a short form ADAMTS-18 presents in vivo
      are not clear. In this study, we first identified that the thrombin cleavage site
      is between Arg775 and Ser776 by thrombin cleavage of ADAMTS-18 peptide following
      mass spectrum assay. We then showed that a short form ADAMTS-18 presents in
      brain, kidney, lung, and testicle from C57BL/6 mouse embryo. Since alternative
      form of ADAMTS-18 could be a mechanism to regulate its activity, we then
      investigated the mechanism involves in the generation of ADAMTS-18 short form.
      However, neither protease inhibitors nor mutations in catalytic domain of ADAMTS
      18 have any significant effect on the generation of ADAMTS-18 short form. Thus,
      our data demonstrate a thrombin cleavage site and confirm a short form of ADAMTS
      18 presents in vivo.

PMID- 22386993
TI  - Biomechanical characterization of a desminopathy in primary human myoblasts.
AB  - Heterozygous mutations of the human desmin gene on chromosome 2q35 cause
      hereditary and sporadic myopathies and cardiomyopathies. The expression of mutant
      desmin brings about partial disruption of the extra sarcomeric desmin
      cytoskeleton and abnormal protein aggregation in the sarcoplasm of striated
      muscle cells. The precise molecular pathways and sequential steps that lead from
      a desmin gene defect to progressive muscle damage are still unclear. We tested
      whether mutant desmin changes the biomechanical properties and the intrinsic
      mechanical stress response of primary cultured myoblasts derived from a patient
      carrying a heterozygous R350P desmin mutation. Compared to wildtype controls,
      undifferentiated mutant desmin myoblasts revealed increased cell death and
      substrate detachment in response to cyclic stretch on flexible membranes.
      Moreover, magnetic tweezer microrheometry of myoblasts using fibronectin-coated
      beads showed increased stiffness of diseased cells. Our findings provide the
      first evidence that altered mechanical properties may contribute to the
      progressive striated muscle pathology in desminopathies. We postulate that the
      expression of mutant desmin leads to increased mechanical stiffness, which
      results in excessive mechanical stress in response to strain and consecutively to
      increased mechanical vulnerability and damage of muscle cells.

PMID- 22386994
TI  - T cells stimulate catabolic gene expression by the stromal cells from giant cell
      tumor of bone.
AB  - The factors that promote the localized bone resorption by giant cell tumor of
      bone (GCT) are not fully understood. We investigated whether T cells could
      contribute to bone resorption by stimulating expression of genes for parathyroid
      hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the
      receptor activator of nuclear-factor kappaB ligand (RANKL). Two cell lines,
      Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells.
      Real-time PCR analyses demonstrated a significant increase of all three genes
      following 48h incubation, and PTHrP and MMP-13 gene expression was also increased
      at 24h. Further, we examined the expression of CD40 ligand (CD40L), a protein
      expressed by activated T cells, and its receptor, CD40, in GCT.
      Immunohistochemistry results revealed expression of the CD40 receptor in both the
      stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues
      showed expression of CD40LG, which was absent in cultured stromal cells, and
      suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells
      with CD40L significantly increased expression of the PTHrP and MMP-13 genes.
      Moreover, we show that inhibition of PTHrP with neutralizing antibodies
      significantly decreased MMP13 expression by the stromal cells compared to IgG
      matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene
      expression. These results suggest that T cells may potentiate the catabolic
      effect of GCT.

PMID- 22386995
TI  - Effect of reactive core mat application on bioavailability of hydrophobic organic
      compounds.
AB  - Sediment remediation techniques to limit the bioavailability of contaminants are
      of special interest due to related acute or chronic toxicities associated with
      sediment contaminants. Bioavailability in aquatic sediments can be particularly
      problematic due to their accessibility to food chain biota, and interactions with
      surface and ground water. The effect of a reactive core mat (RCM) containing
      organoclay on the bioavailability of hydrophobic organic compounds (HOCs) (i.e.,
      PCBs and naphthalene) was studied using oligochaete worms (Lumbriculus
      variegatus). Sediment sampled from the Neponset River (Milton, MA) with 10 ppm
      background PCB contamination was used in the experimental study. The objective of
      this study is to investigate the difference in HOC concentration of worms exposed
      to: a) a grab sample of contaminated sediment (10.4% total organic carbon); and
      b) an initially clean mixture of sand and organic matter (the so-called biouptake
      layer), placed on top of the RCM-capped sediment during consolidation coupled
      solute transport experiments. In addition to the experimental data, the U.S. Army
      Corps of Engineers (USACE) biota-sediment accumulation factor (BSAF) database was
      validated and used to model biouptake of contaminants for certain cases. Results
      indicate that RCM capping reduced the average bioavailability of both PCBs and
      naphthalene by a factor of about 50. In fact, worms exposed to the RCM-protected
      biouptake layer show virtually the same HOC concentrations as those measured in
      the control worm samples.

PMID- 22386996
TI  - Association between dust weather and number of admissions for patients with
      respiratory diseases in spring in Lanzhou.
AB  - Controlling the confounding factors on respiratory hospitalizations such as long
      term trend, meteorological factor, atmospheric pollution, and calendar effect,
      the research is designed to study the effect of sand-dust weather on respiratory
      diseases from 2001 to 2005 in Lanzhou City on the basis of the semi-parametric
      generalized additive model (GAM). The results indicate that there is an
      association between sand-dust weather and the increase in respiratory
      hospitalizations, and with lagging effect. There are gender and age differences
      in the effect of sand-dust weather on health, on male severer than on female (RR
      value being 1.148 for male, while 1.144 for female without statistical
      significance), and much greater on the aged >= 65 years than on < 65 years (RR
      value being 1.266 for >= 65 yr, and 1.119 for < 65 yr).

PMID- 22386997
TI  - [Astigmatism correction with Excimer laser].
AB  - Excimer laser is the best and the more used technique for Astigmatism correction.
      Lasik is generally preferred to PRK and must be the choice for hyperopic and mix
      astigmatisms. Myopic astigmatisms are the easier cases to treat: the length of
      the photoablation is placed on the flat meridian. Hyperopic and mix astigmatisms
      are more difficult to correct because they are more technically demanding and
      because the optical zone of the photoablation must be large. Flying spots lasers
      are the best for these cases. The most important point is to trace the
      photoablation very precisely on the astigmatism axis. The use of eye trackers
      with iris recognition or a preoperative marking of the reference axis avoid
      cyclotorsion or a wrong position of the head. Irregular astigmatism are better
      corrected with topoguided or wavefront guided photoablations.

PMID- 22386998
TI  - Nanotechnologies for the treatment of water, air and soil.

PMID- 22386999
TI  - Electrochemical depassivation for recovering Fe(0) reactivity by Cr(VI) removal
      with a permeable reactive barrier system.
AB  - A new electrochemical permeable reactive barrier (Electro-PRB) system for removal
      of hexavalent chromium [Cr(VI)] using Fe(0) meshes was developed. Electro-PRB was
      found to be effective for electrochemical depassivation of Fe(0) to remove Cr(VI)
      during treatment. During initial treatment, Cr(VI) removal rates decreased with
      time, due to loss of Fe(0) reactivity by mineral fouling. After Fe(0) was
      passivated, electrochemical depassivation was introduced for different
      electrolysis times to recover Fe(0) reactivity. It was found that there was
      approximately 100.4-131.3% initial removal rate recovery, due to the
      electrochemical break down of precipitates on the Fe(0) surfaces. During the
      treatment, the decreasing pH and increasing oxidation-reduction Potential (ORP)
      of the effluent implied the passivation of Fe(0) surfaces. Scanning electron
      microscope analysis of acid-washed, electrochemically depassivated, and
      passivated Fe(0) confirmed the efficiency of Elecro-PRB in the recovery Fe(0)
      reactivity. The results indicate that the Electro-PRB system proposed here is
      capable of recovering the reactivity of Fe(0), which may prolong the operation of
      Cr(VI) removal processes.

PMID- 22387000
TI  - Effect of the cathode material on the removal of nitrates by electrolysis in non
      chloride media.
AB  - In this work, the effect of the cathode material (conductive diamond, stainless
      steel, silicon carbide, graphite or lead) and the current density (150-1400 A m(
      2)) on the removal of nitrates from aqueous solutions is studied by electrolysis
      in non-divided electrochemical cells equipped with conductive diamond anodes,
      using sodium sulphate as the electrolyte. The results show that the cathode
      material very strongly influences both the process performance and the product
      distribution. The main products obtained are gaseous nitrogen (NO, N(2)O and
      NO(2)) and ammonium ions. Nitrate removal follows first order kinetics, which
      indicates that the electrolysis process is controlled by mass transfer.
      Furthermore, the stainless steel and graphite cathodes show a great selectivity
      towards the production of ammonium ions, whereas the silicon carbide cathode
      leads to the highest formation of gaseous nitrogen, which production is promoted
      at low current densities.

PMID- 22387003
TI  - New insights into chronic inflammation-induced immunosuppression.
AB  - Chronic inflammation is a common factor linking various pathologies that differ
      in their etiology and physiology such as cancer, autoimmune diseases, and
      infections. At a certain stage of each of these diseases, while the chronic
      inflammation proceeds, some key players of the immune system become
      immunosuppressed as natural killer (NK) cells and T cells. The suppressive
      environment induced during chronic inflammation is governed by a complex
      processes characterized by the accumulation and activation of immune suppressor
      cells, pro-inflammatory cytokines, chemokines, growth and angiogenic factors, and
      by the activation of several inflammatory signaling pathways mediated
      predominantly by NFkappaB and STAT3 transcription factors. A substantial body of
      evidence supports the notion that the development of a suppressive environment
      during chronic inflammation limits the success of immune-based and conventional
      therapies, skewing the balance in favor of a developing pathology. Thus,
      appropriate, well-designed and fine tuned immune interventions that could resolve
      inflammatory responses and associated immunosuppression could enhance disease
      regression and reinforce successful responses to a given therapy. This review
      describes the interrelationship between chronic inflammation and induced
      immunosuppression, and explains the current evidence linking inflammation and
      pathological processes, as found in cancer. We further highlight potential
      strategies, harnessing the immunosuppressive environment in treating autoimmune
      diseases and facilitating transplantation. In parallel, we emphasize the use of
      modalities to combat chronic inflammation-induced immunosuppression in cancer, to
      enhance the success of immune-based therapies leading to tumor regression. In
      both cases, the urgent necessity of identifying biomarkers for the evaluation of
      host immune status is discussed, with the goal of developing optimal personalized
      treatments.

PMID- 22387001
TI  - Role of RhoA-specific guanine exchange factors in regulation of endomitosis in
      megakaryocytes.
AB  - Polyploidization can precede the development of aneuploidy in cancer.
      Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled
      developmental process critical for efficient platelet production via unknown
      mechanisms. Using primary cells, we demonstrate that the guanine exchange factors
      GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for
      RhoA activation during cytokinesis, must be downregulated for Mk
      polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1
      downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation.
      Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in
      proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which
      polyploidization is prevented in Mks lacking Mkl1, which is mutated in
      megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1
      knockdown alone rescues this ploidy defect. These mechanistic insights enhance
      our understanding of normal versus malignant megakaryocytopoiesis, as well as
      aberrant mitosis in aneuploid cancers.

PMID- 22387002
TI  - Trophoblasts regulate the placental hematopoietic niche through PDGF-B signaling.
AB  - The placenta is a hematopoietic organ that supports hematopoietic stem/progenitor
      cell (HSPC) generation and expansion without promoting differentiation. We
      identified PDGF-B signaling in trophoblasts as a key component of the unique
      placental hematopoietic microenvironment that protects HSPCs from premature
      differentiation. Loss of PDGF-B or its receptor, PDGFRbeta, induced definitive
      erythropoiesis in placental labyrinth vasculature. This was evidenced by
      accumulation of CFU-Es and actively proliferating definitive erythroblasts that
      clustered around central macrophages, highly reminiscent of erythropoiesis in the
      fetal liver. Ectopic erythropoiesis was not due to a requirement of PDGF-B
      signaling in hematopoietic cells but rather in placental trophoblasts, which
      upregulated Epo in the absence of PDGF-B signaling. Furthermore, overexpression
      of hEPO specifically in the trophoblasts in vivo was sufficient to convert the
      placenta into an erythropoietic organ. These data provide genetic evidence of a
      signaling pathway that is required to restrict erythroid differentiation to
      specific anatomical niches during development.

PMID- 22387004
TI  - Arx is required for normal enteroendocrine cell development in mice and humans.
AB  - Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in
      metabolism, digestion, satiety and lipid absorption, yet their development
      remains poorly understood. Here we show that Arx, a homeodomain-containing
      transcription factor, is required for the normal development of mouse and human
      enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3
      (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone
      producing cells. In mice, removal of Arx from the developing endoderm results in
      a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK
      , secretin-producing cell populations and an increase of somatostatin-expressing
      cells. This phenotype is also observed in mice with endocrine-progenitor-specific
      Arx ablation suggesting that Arx is required in the progenitor for
      enteroendocrine cell development. In addition, depletion of human ARX in
      developing human intestinal tissue results in a profound deficit in expression of
      the enteroendocrine cell markers CCK, secretin and glucagon while expression of a
      pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained
      unchanged. Taken together, our findings uncover a novel and conserved role of Arx
      in mammalian endocrine cell development and provide a potential cause for the
      chronic diarrhea seen in both humans and mice carrying Arx mutations.

PMID- 22387006
TI  - Health-related quality of life in patients with lung cancer: validation of the
      Mexican-Spanish version and association with prognosis of the EORTC QLQ-LC13
      questionnaire.
AB  - INTRODUCTION: Lung cancer (LC) is the first cause of cancer-related mortality
      worldwide and health-related quality of life (HRQL) is a fundamental outcome for
      evaluating treatment results. Our objective was to validate the Mexican-Spanish
      versions of the European Organisation for Research and Treatment of Cancer
      (EORTC) Quality-of-Life QLQ-LC13 disease-specific questionnaire module in Mexican
      patients with LC; and to explore the possible prognostic role of HRQL data.
      METHODS: Translation procedures followed EORTC guidelines. Both instruments were
      completed by patients with LC. Tests for reliability and validity were performed.
      A subset of patients was administered HRQL evaluations before and after
      chemotherapy. HRQL was associated with prognosis in chemotherapy-naive patients.
      The protocol was approved by the Institute's Ethics Committee. RESULTS: One
      hundred fifty three patients (mean age, 60.3 years; 84 females and 69 males)
      completed both questionnaires. Compliance rates were high, and the questionnaires
      were well accepted. Nine of 10 multi-item scales of both questionnaires presented
      Cronbach's alpha coefficients > 0.7. Multi-trait scaling analysis demonstrated
      good convergent and discriminant validity. Patients with better Karnofsky or
      Eastern Cooperative Oncology Group (ECOG) performance status reported better
      functional HRQL scores. Different scales in the EORTC QLQ-C30 and EORTC QLQ-LC13
      questionnaires were accurately related with clinical characteristics. Functional
      as well as disease-symptom scales improved after chemotherapy, but treatment side
      effects scales worsened in test-retest analysis. Better role functioning and
      absence of thoracic pain scales were associated with longer overall survival (OS)
      (p = 0.009 and p = 0.035, respectively). CONCLUSION: The Mexican-Spanish versions
      of the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires are reliable and valid for
      HRQL measurement in Mexican patients with LC and can be used in clinical trials.

PMID- 22387005
TI  - Prognostic impact of cancer stem cell-related markers in non-small cell lung
      cancer patients treated with induction chemoradiotherapy.
AB  - The expression of several cancer stem cell (CSC)-related markers has been
      confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to
      clarify the clinical role of CSC-related markers in patients with NSCLC
      undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically
      diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin
      concurrently with thoracic radiation followed by surgery were examined in this
      study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1)
      were examined using immunohistochemical staining in surgically resected
      specimens. Among the 50 patients, 20 patients had no residual tumor cells in the
      resected specimen when examined pathologically; CSC-related marker expressions
      and their correlation to survival were evaluated in the other 30 patients. After
      a median follow-up period of 72 months, the 5-year overall survival rate of the
      patients with CD133-positive or ALDH1-positive specimens was significantly worse
      than that of the patients with both CD133-negative and ALDH1-negative expressions
      (44.9% vs. 90.0%, respectively; P = 0.042). In a multivariate analysis, CD133 and
      ALDH1 negativity (P = 0.047) and cN2-3 single station metastasis (P = 0.03) were
      significant independent prognostic factors for prolonged survival. The
      expressions of CSC-related markers after CRT were significantly correlated with a
      poor prognosis in patients with NSCLC. The development of therapeutic strategies
      including adjuvant therapy that take CSC-related marker positivity into
      consideration is likely to be a key factor in further improvements of the
      prognosis of patients undergoing trimodality therapy.

PMID- 22387007
TI  - Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer:
      mechanism for immune evasion?
AB  - Cytotoxic CD8(+) T-cells mount immune responses to cancer via cytotoxic pathways
      including granzyme B. Cancer cells are also known to develop immune evasion
      mechanisms. We hypothesised that lung cancer cells would over-express the
      granzyme B-inhibitor, proteinase inhibitor-9 (PI-9) and down-regulate granzyme B
      expression by neighbouring CD8(+) T-cells. We investigated PI-9 expression in
      lung cancer cell lines, and primary lung cancer cells obtained at curative lung
      resection from cancer patients with/without chronic obstructive pulmonary disease
      (COPD). Granzyme B and PI-9 expression was also determined in CD8(+) T-cells from
      the cancer and non-cancer areas of resected lung tissue and from bronchoalveolar
      lavage (BAL). We then evaluated the effects of conditioned media from lung cancer
      cell lines on granzyme B expression and the cytotoxic activity of CD8(+) T-cells.
      PI-9 was highly expressed in lung cancer cell lines. Increased PI-9 expression
      was also observed in primary cancer cells vs. epithelial cells from non-cancer
      tissue or bronchial brushing-derived normal primary large airway epithelial
      cells. Expression significantly correlated with cancer stage. Significantly
      reduced granzyme B was noted in CD8(+) T-cells from cancer vs. non-cancer tissue.
      Granzyme B production by CD8(+) T-cells was reduced in the presence of
      conditioned media from lung cancer cell lines. Our data suggest that lung cancer
      cells utilise their increased PI-9 expression to protect from granzyme B-mediated
      cytotoxicity as an immune evasion mechanism, a function that increases with lung
      cancer stage.

PMID- 22387008
TI  - Introducing taxes, subsidies or both: the effects of various food pricing
      strategies in a web-based supermarket randomized trial.
AB  - OBJECTIVE: Fiscal policies may form a solution in improving dietary intake. This
      study aimed to examine the effectiveness of varying taxing and subsiding schemes
      to stimulate healthier food purchases. METHODS: A randomized controlled trial
      with three levels of price reduction on healthy foods (no; 25%; 50%)*three levels
      of price increase on unhealthy foods (5%; 10%; 25%) factorial design was used.
      150 participants were randomized into one of nine conditions and were asked to
      purchase groceries at a web-based supermarket. Data were collected in the
      Netherlands in January-February 2010 and analyzed using analysis of covariance.
      RESULTS: Subjects receiving 50% discount purchased significantly more healthy
      foods than subjects receiving no (mean difference=6.62 items, p<0.01) or 25%
      discount (mean difference=4.87 items, p<0.05). Moreover, these subjects purchased
      more vegetables (mean difference=821 g;p<0.05 compared to no discount). However,
      participants with the highest discount also purchased significantly more
      calories. No significant effects of the price increases on unhealthy foods were
      found. CONCLUSION: Price decreases are effective in stimulating healthy food
      purchases, but the proportion of healthy foods remains unaffected. Price
      increases up to 25% on unhealthier products do not significantly affect food
      purchases. Future studies are important to validate these results in real
      supermarkets and across different countries.

PMID- 22387009
TI  - Improvement of the lipid profile with exercise in obese children: a systematic
      review.
AB  - OBJECTIVE: The objective of this systematic review was to assess the
      effectiveness of different physical exercise interventions on the lipid profile
      (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein
      cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG)) of obese
      children. METHOD: A computerized search was made of seven databases using
      keywords. Effect sizes (ES) and 95% confidence intervals were calculated, and the
      heterogeneity (I(2)) of the studies was estimated using Cochran's Q-statistic
      applied to the effect size means. The studies were grouped according to the
      intervention program-aerobic alone or combined (aerobic fitness, strength, and
      flexibility). RESULTS: Seven studies were selected for review as satisfying the
      inclusion criteria. Six were randomized controlled trials (n=318) and one was a
      controlled clinical trial (groups not randomly assigned) (n=38). The main
      cumulative evidence indicates that the programs based on aerobic exercise alone
      have a moderate (ES=-0.49; I2=87) and a large effect (ES=-0.55; I2=77) on LDL-C
      and TG concentrations, respectively; and the programs based on combined exercise
      have a moderate effect (ES=0.50; I2=0) on HDL-C concentration. CONCLUSIONS: The
      programs based on aerobic exercise (60 min, 3 times/week, <=75% maximum heart
      rate) improve the LDL-C and TG concentrations. Moreover, the programs based on
      combined exercise (>=60 min, >75% maximum heart rate) also improve the HDL-C
      concentration.

PMID- 22387010
TI  - Calcium signaling in closely related protozoan groups (Alveolata): non-parasitic
      ciliates (Paramecium, Tetrahymena) vs. parasitic Apicomplexa (Plasmodium,
      Toxoplasma).
AB  - The importance of Ca2+-signaling for many subcellular processes is well
      established in higher eukaryotes, whereas information about protozoa is
      restricted. Recent genome analyses have stimulated such work also with
      Alveolates, such as ciliates (Paramecium, Tetrahymena) and their pathogenic close
      relatives, the Apicomplexa (Plasmodium, Toxoplasma). Here we compare Ca2+
      signaling in the two closely related groups. Acidic Ca2+ stores have been
      characterized in detail in Apicomplexa, but hardly in ciliates. Two-pore channels
      engaged in Ca2+-release from acidic stores in higher eukaryotes have not been
      stingently characterized in either group. Both groups are endowed with plasma
      membrane- and endoplasmic reticulum-type Ca2+-ATPases (PMCA, SERCA),
      respectively. Only recently was it possible to identify in Paramecium a number of
      homologs of ryanodine and inositol 1,3,4-trisphosphate receptors (RyR, IP3R) and
      to localize them to widely different organelles participating in vesicle
      trafficking. For Apicomplexa, physiological experiments suggest the presence of
      related channels although their identity remains elusive. In Paramecium, IP3Rs
      are constitutively active in the contractile vacuole complex; RyR-related
      channels in alveolar sacs are activated during exocytosis stimulation, whereas in
      the parasites the homologous structure (inner membrane complex) may no longer
      function as a Ca2+ store. Scrutinized comparison of the two closely related
      protozoan phyla may stimulate further work and elucidate adaptation to parasitic
      life. See also "Conclusions" section.

PMID- 22387012
TI  - Mitochondrial regulation of CRAC channel-driven cellular responses.
AB  - One widespread and conserved Ca(2+) entry pathway in eukaryotic cells is the
      store-operated CRAC channel and Ca(2+) entry through these channels activates a
      disparate array of cellular responses. Under physiological conditions,
      mitochondria are important regulators of CRAC channel gating. Through these
      actions, mitochondria help control a range of spatially and temporally distinct
      CRAC channel-driven responses including enzyme activation, secretion,
      intercellular communication through paracrine signals and gene expression.

PMID- 22387011
TI  - Is ryanodine receptor a calcium or magnesium channel? Roles of K+ and Mg2+ during
      Ca2+ release.
AB  - The ryanodine receptor (RyR) is a poorly selective channel that mediates Ca(2+)
      release from intracellular Ca(2+) stores. How RyR's selectivity between the
      physiological cations K(+), Mg(2+), and Ca(2+) affects single-channel Ca(2+)
      current amplitude is examined using a recent model of RyR permeation. It is found
      that K(+) provides the vast majority of the countercurrent (through RyR itself)
      that is needed to prevent the sarcoplasmic reticulum (SR) membrane potential from
      changing and stopping Ca(2+) release. Moreover, intra-pore competition between
      Ca(2+) and Mg(2+) defines single RyR Ca(2+) current amplitude. Since both
      [Mg(2+)] and [Ca(2+)](SR) can change during pathophysiological conditions, the
      RyR unitary Ca(2+) current amplitude during Ca(2+) release may change
      significantly due to this Ca(2+)/Mg(2+) competition. Compared to the classic
      action of Mg(2+) on RyR open probability, these Ca(2+) current amplitude changes
      have as large or larger effects on overall RyR Ca(2+) mobilization. A new aspect
      of RyR divalent versus monovalent selectivity is also identified where this kind
      of selectivity decreases as divalent concentration increases.

PMID- 22387013
TI  - Multicentric carpotarsal osteolysis is caused by mutations clustering in the
      amino-terminal transcriptional activation domain of MAFB.
AB  - Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia
      characterized by aggressive osteolysis, particularly affecting the carpal and
      tarsal bones, and is frequently associated with progressive renal failure. Using
      exome capture and next-generation sequencing in five unrelated simplex cases of
      MCTO, we identified previously unreported missense mutations clustering within a
      51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A
      further six unrelated simplex cases with MCTO were also heterozygous for
      previously unreported mutations within this same region, as were affected members
      of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor
      that negatively regulates RANKL-induced osteoclastogenesis and is essential for
      normal renal development. Identification of this gene paves the way for
      development of novel therapeutic approaches for this crippling disease and
      provides insight into normal bone and kidney development.

PMID- 22387014
TI  - Genetically determined partial complement C4 deficiency states are not
      independent risk factors for SLE in UK and Spanish populations.
AB  - Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease.
      Complete deficiency of complement component C4 confers strong genetic risk for
      SLE. Partial C4 deficiency states have also shown association with SLE, but
      despite much effort over the last 30 years, it has not been established whether
      this association is primarily causal or secondary to long-range linkage
      disequilibrium. The complement C4 locus, located in the major histocompatibility
      complex (MHC) class III region, exhibits copy-number variation (CNV) and C4
      itself exists as two paralogs, C4A and C4B. In order to determine whether partial
      C4 deficiency is an independent genetic risk factor for SLE, we investigated C4
      CNV in the context of HLA-DRB1 and MHC region SNP polymorphism in the largest and
      most comprehensive complement C4 study to date. Specifically, we genotyped 2,207
      subjects of northern and southern European ancestry (1,028 SLE cases and 1,179
      controls) for total C4, C4A, and C4B gene copy numbers, and the loss-of-function
      C4 exon 29 CT indel. We used multiple logistic regression to determine the
      independence of C4 CNV from known SNP and HLA-DRB1 associations. We clearly
      demonstrate that genetically determined partial C4 deficiency states are not
      independent risk factors for SLE in UK and Spanish populations. These results are
      further corroborated by the lack of association shown by the C4A exon 29 CT
      insertion in either cohort. Thus, although complete homozygous deficiency of
      complement C4 is one of the strongest genetic risk factors for SLE, partial C4
      deficiency states do not independently predispose to the disease.

PMID- 22387015
TI  - Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient
      canonical FGF signaling.
AB  - Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone
      formation during embryonic development. Both gain and loss-of-function studies in
      mice have shown that FGFR2 maintains a critical balance between the proliferation
      and differentiation of osteoprogenitor cells. We have identified de novo FGFR2
      mutations in a sporadically occurring perinatal lethal skeletal dysplasia
      characterized by poor mineralization of the calvarium, craniosynostosis,
      dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles,
      osteopenia, and bent long bones. Histological analysis of the long bones revealed
      that the growth plate contained smaller hypertrophic chondrocytes and a thickened
      hypercellular periosteum. Four unrelated affected individuals were found to be
      heterozygous for missense mutations that introduce a polar amino acid into the
      hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell
      based assay, we determined that these mutations selectively reduced plasma
      membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to
      extracellular FGF. All together, these clinical and molecular findings are
      separate from previously characterized FGFR2 disorders and represent a distinct
      skeletal dysplasia.

PMID- 22387016
TI  - Mutations in CTC1, encoding the CTS telomere maintenance complex component 1,
      cause cerebroretinal microangiopathy with calcifications and cysts.
AB  - Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare
      multisystem disorder characterized by extensive intracranial calcifications and
      cysts, leukoencephalopathy, and retinal vascular abnormalities. Additional
      features include poor growth, skeletal and hematological abnormalities, and
      recurrent gastrointestinal bleedings. Autosomal-recessive inheritance has been
      postulated. The pathogenesis of CRMCC is unknown, but its phenotype has key
      similarities with Revesz syndrome, which is caused by mutations in TINF2, a gene
      encoding a member of the telomere protecting shelterin complex. After a whole
      exome sequencing approach in four unrelated individuals with CRMCC, we observed
      four recessively inherited compound heterozygous mutations in CTC1, which encodes
      the CTS telomere maintenance complex component 1. Sanger sequencing revealed
      seven more compound heterozygous mutations in eight more unrelated affected
      individuals. Two individuals who displayed late-onset cerebral findings, a normal
      fundus appearance, and no systemic findings did not have CTC1 mutations, implying
      that systemic findings are an important indication for CTC1 sequencing. Of the 11
      mutations identified, four were missense, one was nonsense, two resulted in in
      frame amino acid deletions, and four were short frameshift-creating deletions.
      All but two affected individuals were compound heterozygous for a missense
      mutation and a frameshift or nonsense mutation. No individuals with two
      frameshift or nonsense mutations were identified, which implies that severe
      disturbance of CTC1 function from both alleles might not be compatible with
      survival. Our preliminary functional experiments did not show evidence of
      severely affected telomere integrity in the affected individuals. Therefore,
      determining the underlying pathomechanisms associated with deficient CTC1
      function will require further studies.

PMID- 22387018
TI  - Molecular interactions between selected sodium salts of bile acids and morphine
      hydrochloride.
AB  - The objective of this study was to understand the prolonged analgesic action of
      morphine hydrochloride observed in the presence of sodium 12
      oxochenodeoxycholanate. Based on literature, this phenomenon may be due to the
      formation of aggregates in the cell between the molecules of bile acids and
      morphine. In addition to the sodium 12-oxochenodeoxycholanate, the present
      investigation also included salts of cholic and 7-oxodeoxycholic acids.
      Saturation transfer difference NMR experiments showed that morphine binds to the
      bile acid molecule close to the aromatic protons H1 and H2 provided that the
      concentration of the bile acid salt approaches the critical micellar
      concentration (CMC). The spin-lattice relaxation times (T(1)) of the affected
      protons decrease significantly in the presence of micellar solutions of the bile
      acid salts, and the most pronounced change in T(1) was observed for sodium 7
      oxodeoxycholate. Diffusion-ordered NMR experiments suggested that morphine
      hydrochloride can interact only with sodium 7-oxochenodeoxycholate. It can be
      supposed that the molecular ratio of sodium 7-oxodeoxycholate and morphine
      hydrochloride in the mixed micelle is 2:1. The CMC values of mixed micelles do
      not differ from the CMC values of the micelle constituents, which suggests that
      the binding of morphine hydrochloride does not perturb the hydrophobic domain of
      the bile acid molecule. In the presence of bile acids, the transfer rate constant
      (k(12)) of morphine hydrochloride from the buffered aqueous solution to
      chloroform (model of the cell membrane) shows a decrease. A significant decrease
      of the k(12) was also observed in the presence of micellar solutions. Kinetic
      measurements indicated that, in addition to micellar interaction between morphine
      hydrochloride and sodium salts of bile acids, a complex may also be formed in
      chloroform via hydrogen bonds formed between the drug and bile acid molecules.

PMID- 22387017
TI  - Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region.
AB  - Age at the onset of motor symptoms in Huntington disease (HD) is determined
      largely by the length of a CAG repeat expansion in HTT but is also influenced by
      other genetic factors. We tested whether common genetic variation near the
      mutation site is associated with differences in the distribution of expanded CAG
      alleles or age at the onset of motor symptoms. To define disease-associated
      single-nucleotide polymorphisms (SNPs), we compared 4p16.3 SNPs in HD subjects
      with population controls in a case:control strategy, which revealed that the
      strongest signals occurred at a great distance from the HD mutation as a result
      of "synthetic association" with SNP alleles that are of low frequency in
      population controls. Detailed analysis delineated a prominent ancestral haplotype
      that accounted for ~50% of HD chromosomes and extended to at least 938 kb on
      about half of these. Together, the seven most abundant haplotypes accounted for
      ~83% of HD chromosomes. Neither the extended shared haplotype nor the individual
      local HTT haplotypes were associated with altered CAG-repeat length distribution
      or residual age at the onset of motor symptoms, arguing against modification of
      these disease features by common cis-regulatory elements. Similarly, the 11 most
      frequent control haplotypes showed no trans-modifier effect on age at the onset
      of motor symptoms. Our results argue against common local regulatory variation as
      a factor influencing HD pathogenesis, suggesting that genetic modifiers be sought
      elsewhere in the genome. They also indicate that genome-wide association analysis
      with a small number of cases can be effective for regional localization of
      genetic defects, even when a founder effect accounts for only a fraction of the
      disorder.

PMID- 22387019
TI  - Improved endothelialization of NiTi alloy by VEGF functionalized nanocoating.
AB  - To improve surface endothelialization of NiTi alloy substrate, a nano-structured
      coating functionalized with vascular endothelial growth factor (VEGF) was
      fabricated via polydopamine (PDOP) as intermediate layer. The successful
      preparation of VEGF conjugated nanocoating was demonstrated by X-ray diffraction
      (XRD), atomic force microscope (AFM), scanning electron microscopy (SEM), and X
      ray photoelectron spectroscopy (XPS), respectively. Inductively coupled plasma
      mass spectrometry (ICP-MS) test showed that the formed nanocoating significantly
      reduced the release of Ni ion from NiTi alloy in simulated body fluid. The
      biological behaviors of endothelial cells adhered to modified NiTi alloy
      substrates, including cell proliferation, cell spreading and production of nitric
      oxide and prostacyclin were investigated in vitro. The results suggest that
      surface functionalization of NiTi alloy substrate with VEGF is beneficial for
      cell growth. The approach presented here affords an alternative for surface
      modification of NiTi implants applied as heart and vascular implant devices.

PMID- 22387020
TI  - Syphilis and prostitution in the socio-medical geographies of Turkey's early
      republican provinces.
AB  - During and after the Ottoman Empire's collapse, Turkey's fledgling public health
      and social services ministry sought to deal with the increasing prevalence of
      syphilis-especially in its rural communities. This article examines the emergence
      of state-led information collection in Turkey during the 1920s and early 1930s
      and the anti-syphilis campaigns that resulted, and thus explores how the state
      created a new medical and moral order surrounding its citizens' sexualities that
      came to focus its gaze upon prostitution. Utilizing information from official
      primary sources, we analyze this transformation as part of a broader process of
      medicalization and state expansion that made syphilis a subject for state
      regulation. Within this context, moral pronouncements regarding the disease,
      traditional medicine, and prostitution and the potential benefits of regulated
      brothels were reframed, represented, and dispersed as directives for public
      health policy. Through this research, we assess how field-based surveys
      contributed ultimately to republican regimes of regulating sex work that still
      persist.

PMID- 22387021
TI  - Letter to the editors: Essentials for an updated epidemiology of laryngeal
      carcinoma.

PMID- 22387022
TI  - Study of the double beta decays of 96Ru and 104Ru.
AB  - In this work we present new improved experimental limits for the partial half
      lives of the double beta processes of (96)Ru and (104)Ru, obtained by means of a
      gamma-ray spectrometry measurement. A disc of metallic Ru of natural isotopic
      abundance was sandwiched between two HPGe-detectors in the 225 m deep underground
      laboratory HADES. After 108 days of measurement, the lower bounds for the partial
      half-lives were up to 6.9*10(19) yr for (96)Ru and 1.9*10(20) yr for (104)Ru.

PMID- 22387023
TI  - Respiratory variation of the extrahepatic bile duct: evaluation with deep
      inspiratory and expiratory MRCP.
AB  - PURPOSE: The purpose of the study was to evaluate the respiratory variation of
      the extrahepatic bile duct in morphology including shape, length and duct
      diameter on the breath-hold magnetic resonance cholangiopancreatography (MRCP)
      obtained during deep inspiration and deep expiration in patients with or without
      biliary diseases. MATERIALS AND METHODS: This study included 102 patients with or
      without biliary diseases. Breath-hold MRCP was obtained twice during the end
      inspiration and the end-expiration. MRCP images were evaluated for the length,
      maximal diameter and "bowing" of the extrahepatic bile duct. RESULTS: In the
      normal group, the mean maximal diameter of the extrahepatic bile duct was
      significantly larger on the end-inspiratory MRCP (8.0 +/- 2.0 mm) than on the end
      expiratory MRCP (7.3 +/- 1.8 mm) (P<.0001), while it was not significantly
      different in the dilated group. In the normal group, 25 (39%) of 65 patients had
      an increase in the mean maximal diameter of more than 1 mm at the end
      inspiration, whereas 4 (11%) of 37 patients in the dilated group had it. The
      bowing of the extrahepatic bile duct on the end-inspiratory MRCP was observed in
      60 (92%) of 65 normal patients, while it was seen in 22 (60%) of 37 patients with
      biliary dilatation (P<.0001). CONCLUSION: Deep inspiratory and expiratory MRCP
      demonstrated the respiratory variations of the extrahepatic bile duct in the
      shape (bowing), length and maximal duct diameter in patients with nondilated bile
      ducts. Awareness of this normal phenomenon will be important for the correct
      interpretation of MRCP in patients with or without biliary diseases.

PMID- 22387024
TI  - A preliminary study of functional abnormalities in aMCI subjects during different
      episodic memory tasks.
AB  - Functional magnetic resonance imaging (fMRI) is an important imaging modality to
      understand the neurodegenerative course of mild cognitive impairment (MCI) and
      early Alzheimer's disease (AD), because the memory dysfunction may occur before
      structural degeneration is obvious. In this research, we investigated the
      functional abnormalities of subjects with amnestic MCI (aMCI) using three
      episodic memory paradigms that are relevant to different memory domains in both
      encoding and recognition phases. Both whole-brain analysis and region-of-interest
      (ROI) analysis of the medial temporal lobes (MTL), which are central to the
      memory formation and retrieval, were used to compare the efficiency of the
      different memory paradigms and the functional difference between aMCI subjects
      and normal control subjects. We also investigated the impact of using different
      functional activation measurements in ROI analysis. This pilot study could
      facilitate the use of fMRI activations in the MTL as a marker for early detection
      and monitoring progression of AD.

PMID- 22387025
TI  - Distinct regulatory mechanisms and functions for p53-activated and p53-repressed
      DNA damage response genes in embryonic stem cells.
AB  - p53 is critical in regulating the differentiation of ES and induced pluripotent
      stem (iPS) cells. Here, we report a whole-genome study of p53-mediated DNA damage
      signaling in mouse ES cells. Systems analyses reveal that binding of p53 at the
      promoter region significantly correlates with gene activation but not with
      repression. Unexpectedly, we identify a regulatory mode for p53-mediated
      repression through interfering with distal enhancer activity. Importantly, many
      ES cell-enriched core transcription factors are p53-repressed genes. Further
      analyses demonstrate that p53-repressed genes are functionally associated with
      ES/iPS cell status while p53-activated genes are linked to differentiation. p53
      activated genes and -repressed genes also display distinguishable features of
      expression levels and epigenetic markers. Upon DNA damage, p53 regulates the self
      renewal and pluripotency of ES cells. Together, these results support a model
      where, in response to DNA damage, p53 affects the status of ES cells through
      activating differentiation-associated genes and repressing ES cell-enriched
      genes.

PMID- 22387026
TI  - Histone H3 lysine 56 methylation regulates DNA replication through its
      interaction with PCNA.
AB  - Histone modifications play important roles in regulating DNA-based biological
      processes. Of the modified sites, histone H3 lysine 56 (H3K56) is unique in that
      it lies within the globular core domain near the entry-exit sites of the
      nucleosomal DNA superhelix and its acetylation state in yeast is a marker for
      newly synthesized histones in transcription, DNA repair, and DNA replication. We
      now report the presence of H3K56 monomethylation (H3K56me1) in mammalian cells
      and find that the histone lysine methytransferase G9a/KMT1C is required for
      H3K56me1 both in vivo and in vitro. We also find that disruption of G9a or H3K56
      impairs DNA replication. Furthermore, H3K56me1 associates with the replication
      processivity factor PCNA primarily in G1 phase of the cell cycle and, directly,
      in vitro. These results find H3K56me1 in mammals and indicate a role for H3K56me1
      as a chromatin docking site for PCNA prior to its function in DNA replication.

PMID- 22387027
TI  - R-loop formation is a distinctive characteristic of unmethylated human CpG island
      promoters.
AB  - CpG islands (CGIs) function as promoters for approximately 60% of human genes.
      Most of these elements remain protected from CpG methylation, a prevalent
      epigenetic modification associated with transcriptional silencing. Here, we
      report that methylation-resistant CGI promoters are characterized by significant
      strand asymmetry in the distribution of guanines and cytosines (GC skew)
      immediately downstream from their transcription start sites. Using innovative
      genomics methodologies, we show that transcription through regions of GC skew
      leads to the formation of long R loop structures. Furthermore, we show that GC
      skew and R loop formation potential is correlated with and predictive of the
      unmethylated state of CGIs. Finally, we provide evidence that R loop formation
      protects from DNMT3B1, the primary de novo DNA methyltransferase in early
      development. Altogether, these results suggest that protection from DNA
      methylation is a built-in characteristic of the DNA sequence of CGI promoters
      that is revealed by the cotranscriptional formation of R loop structures.

PMID- 22387028
TI  - RNA-binding protein HuD controls insulin translation.
AB  - Although expression of the mammalian RNA-binding protein HuD was considered to be
      restricted to neurons, we report that HuD is present in pancreatic beta cells,
      where its levels are controlled by the insulin receptor pathway. We found that
      HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR)
      of preproinsulin (Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA
      levels, but HuD overexpression decreased Ins2 mRNA translation and insulin
      production, and conversely, HuD silencing enhanced Ins2 mRNA translation and
      insulin production. Following treatment with glucose, HuD rapidly dissociated
      from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice
      displayed higher insulin levels in pancreatic islets, while HuD-overexpressing
      mice exhibited lower insulin levels in islets and in plasma. In sum, our results
      identify HuD as a pivotal regulator of insulin translation in pancreatic beta
      cells.

PMID- 22387029
TI  - Intratumoral versus intravenous gene therapy using a transcriptionally targeted
      viral vector in an orthotopic hepatocellular carcinoma rat model.
AB  - PURPOSE: To evaluate the feasibility of intratumoral delivery of adenoviral
      vector carrying a bidirectional two-step transcriptional amplification (TSTA)
      system to amplify transcriptional strength of cancer-specific Survivin promoter
      in a hepatocellular carcinoma model. MATERIALS AND METHODS: MCA-RH7777 cells were
      implanted in rat liver, and tumor formation was confirmed with
      [(18)F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). The
      adenoviral vector studied had Survivin promoter driving a therapeutic gene (tumor
      necrosis factor-alpha-related apoptosis-inducing ligand [TRAIL]) and a reporter
      gene (firefly luciferase [FL]; Ad-pSurvivin-TSTA-TRAIL-FL). Tumor-bearing rats
      were administered Ad-pSurvivin-TSTA-TRAIL-FL intravenously (n = 7) or
      intratumorally (n = 8). For control groups, adenovirus FL under cytomegalovirus
      (CMV) promoter (Ad-pCMV-FL) was administered intravenously (n = 3) or
      intratumorally (n = 3). One day after delivery, bioluminescence imaging was
      performed to evaluate transduction. At 4 and 7 days after delivery, 18F-FDG-PET
      was performed to evaluate therapeutic efficacy. RESULTS: With intravenous
      delivery, Ad-pSurvivin-TSTA-TRAIL-FL showed no measurable liver tumor FL signal
      on day 1 after delivery, but showed better therapeutic efficacy than Ad-pCMV-FL
      on day 7 (PET tumor/liver ratio, 3.5 +/- 0.58 vs 6.0 +/- 0.71; P = .02). With
      intratumoral delivery, Ad-pSurvivin-TSTA-TRAIL-FL showed positive FL signal from
      all tumors and better therapeutic efficacy than Ad-pCMV-FL on day 7 (2.4 +/- 0.50
      vs 5.4 +/- 0.78; P = .01). In addition, intratumoral delivery of Ad-pSurvivin
      TSTA-TRAIL-FL demonstrated significant decrease in tumoral viability compared
      with intravenous delivery (2.4 +/- 0.50 vs 3.5 +/- 0.58; P = .03). CONCLUSIONS:
      Intratumoral delivery of a transcriptionally targeted therapeutic vector for
      amplifying tumor-specific effect demonstrated better transduction efficiency and
      therapeutic efficacy for liver cancer than systemic delivery, and may lead to
      improved therapeutic outcome for future clinical practice.

PMID- 22387030
TI  - Planning ultrasound for percutaneous radiofrequency ablation to treat small (<= 3
      cm) hepatocellular carcinomas detected on computed tomography or magnetic
      resonance imaging: a multicenter prospective study to assess factors affecting
      ultrasound visibility.
AB  - PURPOSE: To assess factors affecting tumor visibility on planning ultrasound (US)
      for percutaneous radiofrequency (RF) ablation to treat small hepatocellular
      carcinomas (HCCs) primarily detected on computed tomography (CT) or magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: Patients referred for planning US
      for percutaneous RF ablation between September 2008 and June 2009 were
      prospectively enrolled from nine institutions in Korea. The first small (<= 3 cm)
      single HCC or new single HCC after treatment was included. The study enrolled 898
      patients (684 men and 214 women, age range 32-86 years). HCCs that were invisible
      on planning US were compared with visible HCCs with respect to tumor size,
      distance between the tumor and the diaphragm, subcapsular location, etiology of
      liver disease, liver cirrhosis, macronodular cirrhosis on US, ascites, Child-Pugh
      class, serum alpha fetoprotein (AFP) level, body mass index (BMI), previous
      treatments for HCC, previous chemoembolization treatments for HCC, institutions,
      and experience of radiologists. RESULTS: Among 898 HCCs, 671 (74.7%) were visible
      on the planning US. In multivariate analysis, tumor size, distance between the
      tumor and the diaphragm, liver cirrhosis, and macronodular cirrhosis were
      statistically significant factors affecting US detection (each P < .05).
      CONCLUSIONS: Smaller tumors, subphrenic location of the tumor, liver cirrhosis,
      and macronodular cirrhosis were independent predictors of invisible tumors on
      planning US.

PMID- 22387031
TI  - Cutis laxa: a review.
AB  - Cutis laxa is a rare disorder of elastic tissue resulting in loose, redundant,
      hypoelastic skin. Both acquired and inherited forms exist, some of which have
      significant systemic manifestations. Here, we review the various forms of cutis
      laxa, with focus on the inherited forms. Recent molecular studies have provided
      many new insights into the causes of cutis laxa and revealed greater genetic
      heterogeneity than previously appreciated.

PMID- 22387032
TI  - The natural history of halo nevi: a retrospective case series.
AB  - BACKGROUND: The time period between onset of depigmentation around the halo nevus
      (HN) to complete resolution of the nevus and halo has not been well studied.
      OBJECTIVE: We sought to better understand the natural history of the HN. METHODS:
      A retrospective chart review of patients with a clinical diagnosis of HN selected
      from a private practice database (1994-2010) was performed. In all, 52 patients
      with 80 HN were identified. The current stage of the HN was determined by a
      follow-up questionnaire and physical examination of 36 patients with 56 HN.
      RESULTS: Seven HN were excised. Of the remaining 49 HN, 51% (25) demonstrated no
      change in the halo or nevus after an average of 4.2 years; 14.3% (7) demonstrated
      partial nevus regression with persistence of the halo after an average of 6.7
      years; 4.1% (2) demonstrated complete involution of the nevus with persistent
      halo depigmentation after an average of 7.7 years; 8.2% (4) demonstrated complete
      nevus involution with some repigmentation of the halo after an average of 11.8
      years; 22.4% (11) demonstrated complete resolution of the nevus with complete
      repigmentation of the halo after an average of 7.8 years. LIMITATION: Some
      subjects were lost to follow-up. The time of initial HN onset was dependent on
      patient recall. CONCLUSION: These results demonstrate that HN typically persist
      for a decade or longer. A subgroup may progress through stages of involution with
      a return to normal-appearing skin, but even these lesions persisted for an
      average of 7.8 years. Education about the prolonged natural history of HN may
      reassure patients and avoid unnecessary excision.

PMID- 22387033
TI  - Multidisciplinary approach to the management of dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is the most common cutaneous
      sarcoma. Tentacle-like extensions of neoplastic cells create a high incidence of
      local recurrence and pose challenges to resection and reconstruction. OBJECTIVE:
      Here we present a multidisciplinary approach to the management of DFSP
      incorporating the expertise of a Mohs micrographic surgeon, surgical oncologist,
      dermatopathologist, and plastic surgeon. METHODS: This was a single-institution,
      retrospective review of a prospectively maintained database of 19 consecutive
      patients who underwent resection and reconstruction of a DFSP from 1998 to 2010.
      All patients underwent Mohs micrographic surgery for mapping of peripheral
      margins (stage I excision), followed by wide local excision for delineation of
      the deep margin (stage II excision). Procedures were performed in consultation
      with a dermatopathologist who confirmed tumor-free margins, and a plastic surgeon
      who performed immediate reconstruction after the wide local excision (stage II
      reconstruction). RESULTS: Nineteen patients were included in this study. The
      average number of Mohs stages required for clearance of peripheral margins was
      2.7 +/- 0.7. The mean time between stage I and II procedures was 16 +/- 11 days.
      The average defect size after the stage II operation was 87.3 cm(2) (range, 9-300
      cm(2)). There were no cases of tumor recurrence. Mean follow-up time was 17
      months (range, 1-53 months). LIMITATIONS: This is a retrospective review of a
      single-institution experience. CONCLUSION: A multidisciplinary approach to the
      management of DFSP optimizes both oncologic and reconstructive outcomes,
      minimizing the risk for local recurrence and limiting the functional and cosmetic
      morbidity associated with surgical resection.

PMID- 22387034
TI  - Deficiency of serum concentration of 25-hydroxyvitamin D in psoriatic patients: a
      case-control study.
AB  - BACKGROUND: Some autoimmune conditions have been associated with reduced vitamin
      D levels, including systemic lupus erythematosus, rheumatoid arthritis, diabetes
      mellitus, and multiple sclerosis. OBJECTIVE: The main objective of this study was
      to analyze the 25-hydroxyvitamin D (OHD) status of patients with psoriasis in
      comparison with control subjects without this disease. METHODS: This case-control
      study included 86 patients (43 with psoriasis and 43 age- and sex-matched control
      subjects) from the outpatient clinic of our hospital dermatology department in
      Granada, Spain. All patients and control subjects were studied during one 4-week
      period to avoid seasonal variations in vitamin D levels. RESULTS: Serum 25-OHD
      levels were significantly lower in psoriatic patients than in control subjects
      even after adjusting for confounding factors in a multivariate analysis (odds
      ratio 2.89, 95% confidence interval 1.02-7.64, P < .03 for vitamin D
      insufficiency). Low 25-OHD levels were negatively associated with C-reactive
      protein (inflammatory activation marker) and body mass index in multiple linear
      regression analysis. Psoriatic patients with body mass index greater than or
      equal to 27 kg/m(2) had a higher risk of 25-OHD insufficiency (sensitivity of
      82.3% and specificity of 51.7%). LIMITATIONS: Further studies with larger numbers
      of patients are required to analyze the pathogenic mechanisms underlying the
      relationship between 25-OHD deficiency and psoriasis. CONCLUSIONS: The 25-OHD
      values are significantly lower in psoriatic patients than in control subjects.
      Low 25-OHD levels are negatively associated with C-reactive protein, an
      inflammatory activation marker, and with obesity. Psoriatic patients with a body
      mass index of 27 or more are likely to have vitamin D insufficiency.

PMID- 22387036
TI  - 4-(dimethylamino)butyric acid@PtNPs as enhancer for solid-state
      electrochemiluminescence aptasensor based on target-induced strand displacement.
AB  - A solid-state electrochemiluminescence (ECL) aptasensor based on target-induced
      aptamer displacement for highly sensitive detection of thrombin was developed
      successfully using 4-(dimethylamino)butyric acid (DMBA)@PtNPs labeling as
      enhancer. Such a special aptasensor included three main parts: ECL substrate, ECL
      intensity amplification and target-induced aptamer displacement. The ECL
      substrate was made by modifying the complex of Pt nanoparticles (PtNPs) and
      tris(2,2-bipyridyl) ruthenium (II) (Ru(bpy)(3)(2+)) (Ru-PtNPs) onto nafion@multi
      walled carbon nanotubes (nafion@MWCNTs) modified electrode surface. A
      complementary thrombin aptamer labeled by DMBA@PtNPs (Aptamer II) acted as the
      ECL intensity amplification. The thrombin aptamer (TBA) was applied to hybridize
      with the labeled complementary thrombin aptamer, yielding a duplex complex of TBA
      Aptamer II on the electrode surface. The introduction of thrombin triggered the
      displacement of Aptamer II from the self-assembled duplex into the solution and
      the association of inert protein thrombin on the electrode surface, decreasing
      the amount of DMBA@PtNPs and increasing the electron transfer resistance of the
      aptasensor and thus resulting large decrease in ECL signal. With the synergistic
      amplification of DMBA and PtNPs to Ru(bpy)(3)(2+) ECL, the aptasensor showed an
      enlarged ECL intensity change before and after the detection of thrombin. As a
      result, the change of ECL intensity has a direct relationship with the logarithm
      of thrombin concentration in the range of 0.001-30 nM. The detection limit of the
      proposed aptasensor is 0.4 pM. Thus, the approach is expected to open new
      opportunities for protein diagnostics in clinical as well as bioanalysis in
      general.

PMID- 22387035
TI  - A consensus approach to wound care in epidermolysis bullosa.
AB  - BACKGROUND: Wound care is the cornerstone of treatment for patients with
      epidermolysis bullosa (EB); however, there are currently no guidelines to help
      practitioners care for these patients. OBJECTIVES: The objective of this study
      was to generate a list of recommendations that will enable practitioners to
      better care for patients with EB. METHODS: An expert panel generated a list of
      recommendations based on the best evidence available. The recommendations were
      translated into a survey, and sent to other EB experts to generate consensus
      using an online-based modified Delphi method. The list was refined and grouped
      into themes and specific recommendations. RESULTS: There were 15 respondents (45%
      response rate), with significant experience in the EB field (>10 years [67%]).
      Respondents included physicians (67%), nurses (17%), and allied health
      professionals (7%). There was more than 85% agreement for all the proposed items.
      These were further refined and grouped into 5 main themes (assessment and
      management of factors that impair healing, patient-centered concerns, local wound
      care, development of an individualized care plan, and organizational support) and
      17 specific recommendations. LIMITATIONS: There is a paucity of scientific
      evidence with most recommendations based on expert opinion. CONCLUSIONS: These
      recommendations will provide practitioners with a framework for caring for these
      patients. Additional scientific research including effectiveness studies for
      everyday practice and expert consensus, may further refine these recommendations.

PMID- 22387037
TI  - Recent trends in antibody based sensors.
AB  - This review details recent advances in the fields of immunosensors and closely
      related immunoassays in the past decade, together with a discussion of possible
      future trends. Immunosensors can be classified by the way in which they transduce
      the signal produced upon the formation of an antibody antigen complex. Recent
      advancements to these methods of detection and transduction are discussed in
      detail, with particular focus on electrochemical, optical, piezoelectric and
      magnetic based sensors. The varying applications of these sensors are also
      discussed. Some of the most significant advances include development of
      immunosensors for the continuous monitoring of analytes, point of care (PoC)
      devices, with lower unit costs, automation, reusability and ease of use.
      Immunosensor technology has advanced at a prolific rate since its conception and
      has grown into a diverse area of ongoing research.

PMID- 22387038
TI  - An aptamer-capture based chromogenic assay for thrombin.
AB  - A simple chromogenic assay for human alpha thrombin is developed through aptamer
      affinity capture and a subsequent enzyme reaction. Thrombin is captured on the
      aptamer-modified magnetic beads, and catalyzes the conversion of chromogenic
      substrates to optically measured products. The measurement of the generated
      products by an absorbance spectrometer allows for the final quantification of
      thrombin. This assay shows high sensitivity by taking advantage of sample
      enrichment and enzyme amplification, and exhibits good specificity by involving
      the selective aptamer binding and the specific enzyme reaction. A concentration
      detection limit of 40 fM can be reached when the tripeptide substrate of tosyl
      Gly-Pro-Arg-p-nitroanilide is used in a 24 h enzyme reaction, and the use of 2h
      enzyme reaction in the assay enables the detection of 400 fM thrombin for a rapid
      analysis. This assay can be applied to detect thrombin in dilute human serum.

PMID- 22387039
TI  - Label-free colorimetric sensor for ultrasensitive detection of heparin based on
      color quenching of gold nanorods by graphene oxide.
AB  - A novel label-free colorimetric strategy was developed for ultrasensitive
      detection of heparin by using the super color quenching capacity of graphene
      oxide (GO). Hexadecyltrimethylammonium bromide (CTAB)-stabilized gold nanorods
      (AuNRs) could easily self-assembly onto the surface of GO through electrostatic
      interaction, resulting in decrease of the surface plasmon resonance (SPR)
      absorption and consequent color quenching change of the AuNRs from deep to light.
      Polycationic protamine was used as a medium for disturbing the electrostatic
      interaction between AuNRs and GO. The AuNRs were prevented from being adsorbed
      onto the surface of GO because of the stronger interaction between protamine and
      GO, showing a native color of the AuNRs. On the contrary, in the presence of
      heparin, which was more easily to combine with protamine, the AuNRs could self
      assembly onto the surface of GO, resulting in the native color disappearing of
      AuNRs. As the concentration of heparin increased, the color of AuNRs would
      gradually fade until almost colorless. The amounts of self-assembly AuNRs were
      proportional to the concentration of heparin, and thereby the changes in the SPR
      absorption and color had been used to monitor heparin levels. Under optimized
      conditions, good linearity was obtained in a range of 0.02-0.28 MUg/mL
      (R=0.9957), and a limit of detection was 5 ng/mL. The simultaneous possession of
      high sensitivity and selectivity, simplicity, rapidity, and visualization enabled
      this sensor to be potentially applicable for ultrasensitive and rapid on-site
      detection toward trace heparin.

PMID- 22387040
TI  - Neuroscience goes on a chip.
AB  - Advances in microelectronics, microfluidics, polymers and microfabrication have
      enabled the creation of disposable lab-on-a-chips (LOCs) as the new tools for
      neuroscience research. The LOCs have been applied for a wide range of
      neurobiology studies, including cellular and molecular biochemical
      experimentations, morphological observations and electrophysiological
      investigations. The integration of miniaturised components leads to analytical
      instrumentations with unprecedented automation, speed of analysis, and
      flexibility. These features make LOCs capable enough to replace their bulky and
      expensive bench-top counterparts. LOCs can be useful for genomic, proteomic,
      epigenomic, peptidomic, connectomic and electrophysiological studies and also as
      effective tools for reductionist neuroscientists. Moreover, they can be applied
      at higher level studies such as developmental neurobiology and behavioural
      investigations. This work provides an in-depth review of LOC platforms for
      neuroscience research. First, we review the essential bench-top neuroscience
      instrumentation as per their functions and features. Next, we present LOC
      counterparts for those bench-top instrumentations. Finally, we offer perspectives
      on persistent challenges and our perception of opportunities based on LOC
      instrumentations in neuroscience research.

PMID- 22387041
TI  - Multi-wall carbon nanotube-polyaniline biosensor based on lectin-carbohydrate
      affinity for ultrasensitive detection of Con A.
AB  - In this paper, a novel method for detecting concanavalin A (Con A) was developed
      based on lectin-carbohydrate biospecific interactions. Multi-wall carbon nanotube
      polyaniline (MWNT-PANI) nanocomposites, synthesized by in situ polymerization,
      were chosen to immobilize d-glucose through the Schiff-base reaction. The
      immobilized D-glucose showed high binding sensitivity and excellent selectivity
      to its target lectin, Con A. Cyclic voltammetry (CV), electrochemical impedance
      spectroscopy (EIS), transmission electron microscopy (TEM) and atomic force
      microscopy (AFM) were applied to characterize the assembly process of the
      modified electrode. Due to the high affinity of Con A for D-glucose and high
      stability of the propounded sensing platform, the fabricated biosensor achieved
      ultrasensitive detection of Con A with good sensitivity, acceptable
      reproducibility and stability. The changes of response current were proportional
      to the Con A concentrations from 3.3 pM to 9.3 nM, with a detection limit of 1.0
      pM. Therefore, the combination of MWNT-PANI nanocomposites and the special
      binding force between lectin and carbohydrate provides an efficient and promising
      platform for the fabrication of bioelectrochemical devices.

PMID- 22387042
TI  - Determining RNA three-dimensional structures using low-resolution data.
AB  - Knowing the 3-D structure of an RNA is fundamental to understand its biological
      function. Nowadays X-ray crystallography and NMR spectroscopy are systematically
      applied to newly discovered RNAs. However, the application of these high
      resolution techniques is not always possible, and thus scientists must turn to
      lower resolution alternatives. Here, we introduce a pipeline to systematically
      generate atomic resolution 3-D structures that are consistent with low-resolution
      data sets. We compare and evaluate the discriminative power of a number of low
      resolution experimental techniques to reproduce the structure of the Escherichia
      coli tRNA(VAL) and P4-P6 domain of the Tetrahymena thermophila group I intron. We
      test single and combinations of the most accessible low-resolution techniques,
      i.e. hydroxyl radical footprinting (OH), methidiumpropyl-EDTA (MPE), multiplexed
      hydroxyl radical cleavage (MOHCA), and small-angle X-ray scattering (SAXS). We
      show that OH-derived constraints are accurate to discriminate structures at the
      atomic level, whereas EDTA-based constraints apply to global shape determination.
      We provide a guide for choosing which experimental techniques or combination of
      thereof is best in which context. The pipeline represents an important step
      towards high-throughput low-resolution RNA structure determination.

PMID- 22387043
TI  - Crystal structure of GAP50, the anchor of the invasion machinery in the inner
      membrane complex of Plasmodium falciparum.
AB  - The glideosome associated protein GAP50 is an essential protein in apicomplexan
      parasites such as Plasmodium, Toxoplasma and Cryptosporidium, several species of
      which are important human pathogens. The 44.6kDa protein is part of a multi
      protein complex known as the invasion machinery or glideosome, which is required
      for cell invasion and substrate gliding motility empowered by an actin-myosin
      motor. GAP50 is anchored through its C-terminal transmembrane helix into the
      inner membrane complex and interacts via a short six residue C-terminal tail with
      other proteins of the invasion machinery in the pellicle of the parasite. In this
      paper we describe the 1.7A resolution crystal structure of the soluble GAP50
      domain from the malaria parasite Plasmodium falciparum. The structure shows an
      alphabetabetaalpha fold with overall similarity to purple acid phosphatases with,
      however, little homology regarding the nature of the residues in the active site
      region of the latter enzyme. While purple acid phosphatases contain a phosphate
      bridged binuclear Fe-site coordinated by seven side chains with the Fe-ions 3.2A
      apart, GAP50 in our crystals contains two cobalt ions each with one protein
      ligand and a distance between the Co(2+) ions of 18A.

PMID- 22387044
TI  - Differential placental expression profile of human Growth Hormone/Chorionic
      Somatomammotropin genes in pregnancies with pre-eclampsia and gestational
      diabetes mellitus.
AB  - The human GH/CSH cluster consisting of one pituitary-expressed (GH1) and four
      placenta-expressed loci has been implicated in maternal metabolic adaptation to
      pregnancy, regulation of intrauterine and postnatal growth. We investigated how
      the mRNA expression profile of placental GH2, CSH1 and CSH2 genes and their
      alternative transcripts correlates with maternal pre-eclampsia (PE) and/or
      gestational diabetes mellitus (GD). The expression of studied genes in PE
      placentas (n=17) compared to controls (n=17) exhibited a trend for reduced
      transcript levels. The alternative transcripts retaining intron 4, GH2-2 and CSH1
      2 showed significantly reduced expression in PE cases without growth restriction
      (P=0.007, P=0.008, respectively). In maternal GD (n=23), a tendency of
      differential expression was detected only for the GH2 gene and in pregnancies
      with large-for-gestational-age newborns. Our results, together with those
      reported by others, are consistent with a pleiotropic effect of placental hGH/CSH
      genes at the maternal-fetal interface relating to the regulation of fetal growth
      and the risk of affected maternal metabolism.

PMID- 22387045
TI  - Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish
      registry of biologics BIOBADASER and a systematic review.
AB  - OBJECTIVE: To evaluate the safety, efficacy, and effectiveness of TNF antagonists
      in patients with sarcoidosis. METHODS: A descriptive study of a case series
      registered in BIOBADASER and a systematic review was performed. The search
      strategy of articles published between 1998 and July 2011 in Medline, Embase, and
      the Cochrane Library included synonyms of sarcoidosis and synonyms of TNF
      antagonists. RESULTS: Seven patients treated with infliximab (IFX) and 1 with
      etanercept (ETN) switched to IFX for inefficacy were registered in BIOBADASER
      2.0. In 3, treatment is still ongoing. Reasons for discontinuation were serious
      adverse events in 2 cases, inefficacy in 2 cases, and complete clinical response
      in 2 cases. Eight serious adverse events were reported. In the selected 69 of
      2262 reports and 1 abstract of the review, 232 patients (89.9%) were treated with
      IFX and 26 (10.0%) were treated with ETN. In 2 randomized clinical trials,
      favorable response of the lung disease was reported with IFX. In other randomized
      clinical trials, no improvement of ocular manifestations was reported with ETN.
      In the cases series, results were diverse. Mean weighted rates of adverse events,
      infections, serious infections, and malignancy were 39.9, 22.1, 5.9, and 1.0 per
      100 patient-years, respectively. CONCLUSIONS: There is insufficient evidence to
      ensure the efficacy of TNF antagonists in sarcoidosis. Nevertheless, IFX may be
      effective in selected manifestations of the disease. Before starting treatment of
      sarcoidosis with IFX, a careful evaluation of the benefit/risk ratio must be
      considered on an individual basis.

PMID- 22387046
TI  - Searching for molecular targets in sarcoma.
AB  - Sarcoma are about 1% of cancers. Within that 1% are widely varied tumors now
      divided into types and subtypes. Sarcoma occur in patients of all ages with
      frequency spread evenly over the human age range. Although the specific cell of
      origin of many sarcoma remains unclear, sarcoma are all tumors of mesenchymal
      origin. The mesenchymal stem cell, a pluripotent cell, which gives rise to varied
      differentiated cells including osteocytes, adipocytes, chondrocytes, muscle
      cells, fibroblasts, neural cells and stromal cells, is the most likely ultimate
      cell of origin for sarcoma. When mesenchymal stem cell genetics go awry and
      malignant transformation occurs sarcoma including osteosarcoma, Ewing's sarcoma,
      chondrosarcoma, rhabdomyosarcoma, synovial sarcoma fibrosarcoma, liposarcoma and
      many others can initiate. Our knowledge of sarcoma genetics is increasing
      rapidly. Two general groups, sarcoma arising from chromosomal translocations and
      sarcoma with very complex genetics, can be identified. Genes that are frequently
      mutated in sarcoma include TP53, NF1, PIK3CA, HDAC1, IDH1 and 2, KDR, KIT and
      MED12. Genes that are frequently amplified in sarcoma include CDK4, YEATS4,
      HMGA2, MDM2, JUN, DNM3, FLT4, MYCN, MAP3K5, GLI1 and the microRNAs miR-214 and
      miR-199a2. Genes that are upregulated in sarcoma include MUC4, CD24, FOXL1,
      ANGPTL2, HIF1alpha, MDK, cMET, TIMP-2, PRL, PCSK1, IGFR-1, TIE1, KDR, TEK, FLT1
      and several microRNAs. While some alterations occur in specific subtypes of
      sarcoma, others cross several sarcoma types. Discovering and developing new
      therapeutic approaches for these relentless diseases is critical. The detailed
      knowledge of sarcoma genetics may allow development of sarcoma subtype-targeted
      therapeutics.

PMID- 22387047
TI  - Antitumor activity of a novel STAT3 inhibitor and redox modulator in non-small
      cell lung cancer cells.
AB  - NSC-743380 is a novel STAT3 inhibitor that suppresses the growth of several NCI
      60 cancer cell lines derived from different tissues and induces regression of
      xenograft tumors in vivo at various doses. To evaluate the antitumor activity of
      NSC-743380 in lung cancer cells, we analyzed the susceptibility of 50 NSCLC cell
      lines to this compound using cell viability assay. About 32% (16 of 50) of these
      cell lines were highly susceptible to this compound, with a 50% inhibitory
      concentration (IC50) of < 1 MUM. In mechanistic studies, the increased numbers of
      apoptotic cells as well as increased PARP cleavage showed that cytotoxic effects
      correlate with apoptosis induction. Treatment with NSC-743380 inhibited
      transcription factor STAT3 activation and induced ROS production in sensitive
      human lung cancer cell lines but not in resistant cells. Blocking ROS generation
      with the antioxidant NDGA dramatically abolished NSC-743380-induced growth
      suppression and apoptosis, but had minimal effect on NSC-743380-induced STAT3
      inhibition, suggesting that STAT3 inhibition is not caused by ROS production.
      Interestingly, knockdown of STAT3 with use of shSTAT3 induced ROS generation and
      suppressed tumor cell growth. Moreover, scavenging ROS induced by STAT3
      inhibition also diminished antitumor activity of STAT3 inhibition. In vivo
      administration of NSC-743380 suppressed tumor growth and p-STAT3 in lung tumors.
      Our results indicate that NSC-743380 is a potent anticancer agent for lung cancer
      and that its apoptotic effects in lung cancer cells are mediated by induction of
      ROS through STAT3 inhibition.

PMID- 22387048
TI  - Clinical predictors of response to treatment in catatonia.
AB  - OBJECTIVE: This study aims at identifying predictors of treatment response to
      lorazepam in catatonia. METHODS: The clinical charts of 107 inpatients, admitted
      over duration of 2 years, with a primary diagnosis of catatonia were examined for
      response to lorazepam trial. Trial was considered as having received 3-6 mg per
      day of lorazepam for at least 3 days. RESULTS: Out of these 107 patients, 99
      received lorazepam and 8 received electroconvulsive therapy as the first line of
      management. There were 32 responders and 67 nonresponders to lorazepam. The
      nonresponders were characterized by rural background (85.1% vs. 62.5%, P=.01),
      longer duration of catatonic symptoms (108.88 vs. 25.12 days, P=.018), mutism
      (63.6% vs. 31.3%, P=.02) and presence of first-rank symptoms like third-person
      auditory discussing-type hallucinations (16.4% vs. 12.0%, P=.03) and made
      phenomena (7.5% vs. 0%, P=.04). The presence of waxy flexibility (12.5% vs. 4.5%,
      P=.03) predicted good response. CONCLUSIONS: This study identifies that longer
      duration of illness, presence of catatonic sign of mutism and certain specific
      phenomena like third-person auditory hallucinations and made phenomena predicted
      poor response to lorazepam in catatonia. This could provide insight into the
      prediction and planning of the appropriate treatment strategies in this
      psychiatric emergency.

PMID- 22387049
TI  - The disturbed blood-brain barrier in human glioblastoma.
AB  - The aim of this article is to describe alterations of the blood-brain barrier
      (BBB) in gliomas. The main clinical problem of human gliomas is the edematous
      swelling and the dramatic increase of intracerebral pressure, also compromising
      healthy areas of the brain. According to our concept, one of the main reasons on
      the cellular level for these clinical problems is the loss or reduction of
      astroglial polarity. Astroglial polarity means the specific accumulation of
      potassium and water channels in the superficial and perivascular astroglial
      endfeet membranes. The most important water channel in the CNS is the astroglial
      water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically
      spectacular way, the so-called orthogonal arrays of particles (OAPs) to be
      observed in freeze-fracture replicas. In brain tumors, but also under conditions
      of trauma or inflammation, these OAPs are redistributed to membrane domains apart
      from endfeet areas. Probably, this dislocation might be due to the degradation of
      the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to
      the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As
      a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised
      directionality of water transport out of the cell, finally to cytotoxic edema.
      This in turn is hypothesized to lead to a breakdown of the BBB characterized by
      disturbed tight junctions, and thus to the development of vasogenic edema.
      However, the mechanism how the loss of polarity is related to the disturbance of
      microvascular tight junctions is completely unknown so far.

PMID- 22387050
TI  - Imatinib resistance due to a novel tri-nucleotide insertion in the SH2/C lobe
      interface of BCR/ABL kinase domain between position K357 and N358.

PMID- 22387051
TI  - Could age modify the effect of genetic variants in IL6 and TNF-alpha genes in
      multiple myeloma?
AB  - Cytokines play a central role in multiple myeloma (MM) pathogenesis thus genetic
      variations within cytokines coding genes could influence MM susceptibility and
      therapy outcome. We investigated the impact of 8 SNPs in these genes in 202 MM
      cases and 235 controls also evaluating their impact on therapy outcome in a
      subset of 91 patients. Despite the overall negative findings, we found a
      significant age-modified effect of IL6 and TNF-alpha SNPs, on MM risk and therapy
      outcome, respectively. Therefore, this observation suggests that genetic
      variation in inflammation-related genes could be an important mediator of the
      complex interplay between ageing and cancer.

PMID- 22387052
TI  - Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: operator and
      institutional requirements for transcatheter valve repair and replacement, part
      1: transcatheter aortic valve replacement.

PMID- 22387053
TI  - Does differential drop-out explain the influence of study design on
      antidepressant response? A meta-analysis.
AB  - BACKGROUND: Response to antidepressants is higher in active comparator relative
      to placebo-controlled clinical trials. Increased patient expectancy in comparator
      trials has been hypothesized to explain this finding, but previous analyses have
      not accounted for the increased drop-out observed in placebo-controlled trials.
      METHODS: A systematic literature review was conducted to identify published
      antidepressant clinical trials reporting data on intent-to-treat (ITT) as well as
      completer patient populations. The influence of participant drop-out on observed
      antidepressant response was investigated by comparing the ITT and completer data
      sets in separate multilevel meta-analyses of antidepressant response in placebo
      controlled and comparator trials. RESULTS: 18 placebo-controlled and 18 active
      comparator studies were available for analysis. Using the intent-to-treat data,
      the odds of responding to medication in comparator trials were 1.9 times the odds
      in placebo-controlled trials (95% CI=1.3-2.7, p=0.001). The same pattern was
      obtained among study completers, in whom the odds of responding to antidepressant
      medication were 1.9 times higher in comparator as opposed to placebo-controlled
      study designs (95% CI=1.2-3.0, p=0.009). LIMITATIONS: Publication bias, the use
      of trial-level summary data, and unreported clinical or demographic differences
      between the ITT and completer patient populations may have influenced the study
      results. CONCLUSIONS: Increased drop-out in placebo-controlled vs. active
      comparator studies of antidepressant medications does not appear to explain the
      difference in response rates between these study types. Rather, increased patient
      expectancy resulting from the certainty of receiving active medication in
      comparator trials may lead to improved response rates.

PMID- 22387054
TI  - The persistence of attachment: complicated grief, threat, and reaction times to
      the deceased's name.
AB  - BACKGROUND: Complicated grief is increasingly recognized as a debilitating
      disorder with significant mental and health consequences. The underlying
      mechanisms of complicated grief remain unclear, however. In the present study, we
      investigated a specific mechanism of complicated grief (CG) derived from
      attachment theory: the accessibility of the deceased's mental representation
      under threat. METHODS: In a matched comparison of complicated (n=26) and
      asymptomatic grievers (n=30), we used an emotional Stroop task following
      subliminal threat or neutral primes to examine the accessibility of mental
      representations of the deceased, current attachment figures, and close others.
      RESULTS: Complicated grievers did not evidence differential accessibility to the
      deceased's mental representation across priming conditions, whereas asymptomatic
      grievers showed reduced accessibility (deactivation) of the deceased's mental
      representation specifically in the threat prime condition. These effects were
      independent of depressive symptoms. Across grievers, attachment anxiety and
      avoidance uniquely predicted accessibility of the deceased's name in the threat
      condition. LIMITATIONS: The limitations of this study are its small sample size
      and reliance on analog attachment threats. CONCLUSIONS: These data support that
      accessibility of the deceased's mental representation in threatening contexts is
      an important component of complicated and asymptomatic grieving and that
      attachment insecurity contributes to a maladaptive reliance on the deceased as an
      attachment figure.

PMID- 22387055
TI  - The Oxford Questionnaire on the Emotional Side-effects of Antidepressants
      (OQuESA): development, validity, reliability and sensitivity to change.
AB  - BACKGROUND: Some patients with major depression report a restricted range of
      emotions that may appear to arise as a side-effect of treatment with
      antidepressants. It is uncertain whether this phenomenon, sometimes called
      emotional blunting, represents residual symptoms of depression or side-effects of
      antidepressant treatment. There is currently no adequate instrument to measure
      this phenomenon. METHODS: A draft questionnaire was developed from patient
      derived qualitative data, refined using cognitive interviewing, and administered
      on three occasions to patients taking antidepressants. Statistical methods
      including factor analysis were used to reduce the size of the draft
      questionnaire, and to assess the performance of the resulting Oxford
      Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA). RESULTS:
      207 patients completed the OQuESA on at least one occasion. Their BDI-II scores
      and self-reported emotional blunting were spread across the possible range. The
      factor analysis resulted in four dimensions: 'not caring', 'emotional
      detachment', 'reduction in positive emotions', and 'general reduction in
      emotions'. The OQuESA appears to be acceptable, valid, and reliable, with
      sensitivity to change. CONCLUSIONS: The OQuESA offers promise as an effective
      self-report measure of the symptoms of emotional blunting in patients with
      depression. It can be used as a clinical tool, to facilitate the identification
      of patients with the syndrome of emotional blunting. It should also be used in
      research studies, to advance our understanding of the nature, causes and
      treatment of this phenomenon.

PMID- 22387056
TI  - Does ragging play a role in medical student depression - cause or effect?
AB  - BACKGROUND: Medical students experience a lot of stress what may contribute to
      symptoms of depression. In this study we set out to look at the environmental
      factors which may be contributing in one medical school in Brazil. METHODS: We
      assessed depressive symptoms using Beck's Depression Inventory in 465 and 267
      medical students in 2001 and 2006 respectively. We explored possible social and
      environmental causes using qualitative data. RESULTS: Nearly 15% scored above the
      cut off for depression in both the samples. Males in the pre-clinical stage in
      2006 showed an increase in depressive symptoms than males in the same cycle in
      2001 (aOR=7.36 [95% CI=0.85-63.5] p=0.07). Qualitative data confirmed that
      factors such as ragging and low social involvement were correlated with
      depressive symptoms in pre-clinical stage males. LIMITATIONS: The sample size was
      small both for quantitative and qualitative aspects of the study. CONCLUSIONS: It
      appears that ragging plays an important role in the genesis of depressive
      symptoms in medical students.

PMID- 22387057
TI  - Clinical and radiological findings in Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS) is a potentially lethal disorder with facial
      dysmorphism, pigmentary skin anomalies, developmental delay and major visceral
      anomalies, such as diaphragmatic hernia, anorectal malformation, and congenital
      heart disease. PKS is causally associated with mosaic tetrasomy of chromosome
      12p. A routine chromosome analysis in peripheral lymphocytes usually fails to
      detect the mosaic state. A prompt diagnosis rests on clinical awareness and a
      subsequent chromosome or molecular analysis in fibroblasts, buccal mucosal cells,
      or bone marrow cells. We report here on three infants with PKS. One infant had
      aortic dilatation, a previously unreported association in PKS. More importantly,
      all infants showed a recognizable, though mild, pattern of skeletal changes
      mainly affecting axial bones, including delayed ossification of the vertebral
      bodies and pubic bones, flared anterior ribs, and broad metaphyses of the long
      bones, particularly of the femora. These skeletal changes should be considered as
      a useful diagnostic sign in PKS. Awareness of the axial skeletal alterations can
      be helpful in prompting clinicians to search for mosaic tetrasomy 12p and perform
      chromosomal analysis in appropriate tissue types.

PMID- 22387058
TI  - Endogenous hyperinsulinaemia and exogenous insulin: a common theme between
      atherosclerosis, increased cancer risk and other morbidities.

PMID- 22387059
TI  - Increased expression of T cell immunoglobulin- and mucin domain-containing
      molecule-3 on natural killer cells in atherogenesis.
AB  - OBJECTIVE: Atherosclerosis (AS) has many features of a chronic inflammatory
      disease in which both adaptive and innate immune cells play roles. Increasing
      evidence has demonstrated the impairment of circulating natural killer (NK) cells
      in atherosclerosis. However, the mechanisms of this impairment remain unclear. We
      previously reported the suppression of NK cell functions by T cell immunoglobulin
      and mucin domain-containing molecule (Tim)-3. Here, we investigated the
      expression of Tim-3 on NK cells and assessed its possible roles in NK loss during
      atherogenesis. METHODS AND RESULTS: Flow cytometry analysis showed increased Tim
      3 expression on peripheral NK cells from patients with AS. This increased
      expression of Tim-3 was significantly related to the levels of serum lipids and
      inflammation markers, C-reactive protein (CRP) and tumor necrosis factor (TNF)
      alpha, which are risk factors for atherogenesis. We detected decreased peripheral
      NK cell number in patients with AS. The NK cell number showed significant inverse
      correlations with Tim-3 expression levels on NK cells and the level of serum TNF
      alpha. Consistently, Tim-3 overexpression reduced NK92 cell number. Blockade of
      Tim-3 protected NK92 cells from TNF-alpha-induced cell death. Similar results
      were obtained with peripheral NK cells from patients with AS. CONCLUSIONS: To the
      best of our knowledge, for the first time, the data from our study provide
      evidence that augmented Tim-3 expression on NK cells plays an important role in
      NK cell loss in atherosclerosis. The augmented Tim-3 expression on NK cells might
      be used as an indicator for disease progression.

PMID- 22387060
TI  - Associations between serum lipoprotein(a) levels and the severity of coronary and
      aortic atherosclerosis.
AB  - To elucidate the associations between Lp(a) levels and coronary and aortic
      atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary
      angiography. Severity of aortic atherosclerosis was represented as plaque scores.
      Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and
      abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels
      increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)),
      21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic
      atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a)
      did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2
      mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal
      plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent
      factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus,
      Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal
      aorta, as well as coronary atherosclerosis.

PMID- 22387061
TI  - Coptisine exert cardioprotective effect through anti-oxidative and inhibition of
      RhoA/Rho kinase pathway on isoproterenol-induced myocardial infarction in rats.
AB  - OBJECTIVE: Because myocardial infarction is a major cause of morbidity and
      mortality worldwide, protecting the heart from the ischemia is the focus of
      intense research. Coptisine is an isoquinoline alkaloid extracted form Coptidis
      Rhizoma. This study aims to elucidate if coptisine is responsible for
      cardioprotection using myocardial infarction (MI) rat models and investigate its
      potential mechanism of action. METHODS: Myocardial infarction was produced in
      rats with 85 mgkg(-1) isoproterenol administered subcutaneously twice at an
      interval of 24 h. The rats were randomized into 7 groups: (I) Normal; (II) ISO;
      (III) ISO+fasudil; (IV) ISO+isosorbide dinitrate (ISDN) and (V-VII) ISO+coptisine
      (25, 50 and 100 mgkg(-1)). Cardiac function and markers of cardiac ischemic were
      assessed after MI. RESULTS: Rats pretreated with coptisine (25, 50 and 100 mgkg(
      1)) for 21 days and received subcutaneously injected with ISO (85 mgkg(-1)) on
      the 20th and 21st day at an interval of 24 h. The results suggested that
      coptisine has strong antioxidant activity, and it can maintain cell membrane
      integrity, ameliorate mitochondrial respiratory dysfunction, reduce myocardial
      cells apoptosis, inhibit RhoA/ROCK expression induced by high-dose isoproterenol
      administration. CONCLUSIONS: Coptisine provided cardioprotection in a model of
      myocardial infarction, and therefore should be considered as a novel adjunctive
      therapy for attenuating myocardial damage.

PMID- 22387062
TI  - Clinical reasoning and patient-centred care in musculoskeletal physiotherapy in
      Portugal--a qualitative study.
AB  - Clinical reasoning has been described as a common process that underpins the
      myriad of tasks in the clinicians' practice. To date clinical reasoning models
      have emerged from research developed in specific and well-developed health care
      and professional cultures, such as those in Australia and the United States, but
      there has been little discussion of their relevance and applicability to other
      cultural settings. The aim of this investigation was to explore clinical
      reasoning processes in a sample of experienced Portuguese musculoskeletal
      physiotherapists. The study focused on clinicians' interaction with their
      patients in order to define and manage clinical problems. Data were collected
      through non-participant observation, semi-structured interviews, memos and field
      notes, and analysed thematically to explore and interpret clinical practice and
      reasoning. Findings highlighted that the clinicians were more likely to carry out
      their reasoning approach as a purely cognitive and clinician centred process.
      Perspectives of clinical reasoning therefore differ between cultures and contexts
      of practice and this has potential implications in the way physiotherapists
      interpret health and illness, their role as clinicians, as well as the patient
      physiotherapist relationship.

PMID- 22387063
TI  - Functional neuroimaging of the 6-OHDA lesion rat model of Parkinson's disease.
AB  - We characterized the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat, a well
      known acute model of Parkinson's disease (PD), with [(18)F]-fluoro-2-deoxy-d
      glucose (FDG) small-animal positron emission tomography (PET), which we compared
      with a drug-induced rotation behavioral test. In the 6-OHDA model, significant
      glucose hypometabolism was present in the primary motor cortex, substantia nigra,
      and pedunculopontine tegmental nucleus on the ipsilateral side. In contrast,
      neuronal activations were observed in the primary somatosensory cortex and
      ventral caudate-putamen area after lesioning. Correlation analysis revealed a
      significant relationship between the behavioral results and the degree of glucose
      metabolism impairment in the primary motor cortex, substantia nigra, and
      pedunculopontine tegmental nucleus. In addition, the pedunculopontine tegmental
      nucleus correlated significantly with the primary somatosensory cortex, the
      ventral caudate-putamen, the substantia nigra, and the primary motor cortex.
      Furthermore, the primary motor cortex also showed significant correlations with
      the substantia nigra. In conclusion, In vivo cerebral mapping of the 6-OHDA
      lesioned rats using [(18)F]-FDG PET showed correspondence at the functional
      levels to the cortico-subcortical network impairment observed in PD patients.

PMID- 22387064
TI  - Interleukin-10 promoter polymorphisms in Chinese patients with Parkinson's
      disease.
AB  - Interleukin-10 (IL-10), an important anti-inflammatory cytokine, may influence
      the risk for the development of onset of sparadic Parkinson's disease (PD) in the
      inflammatory process. In this study, two DNA polymorphisms at IL-10 gene promoter
      (-819 T/C and -592 A/C) were examined in 355 sporadic PD patients and 200 healthy
      controls in Han Chinese Population. For both polymorphisms, no significant
      difference in genotype or allele distribution was found between PD patients and
      the controls. For -819 T/C polymorphisms, there was significant difference in
      genotype distribution between EOPD (EOPD, <50 years of age) patients and each
      healthy-matched control subgroup (P=0.011), as well as between female PD patients
      and each healthy-matched control subgroup (P=0.024), For -592 A/C polymorphisms,
      there were no significant gender- and age-related differences in genotype
      distribution between PD patients and the controls subgroup. Results from our
      study revealed that the IL-10 promoter (-819 and -592) polymorphism is not a risk
      factor of sporadic Parkinson's disease, but the IL-10 promoter -819 polymorphism
      is a risk factor of EOPD and female PD patients in Han Chinese population.

PMID- 22387065
TI  - Social isolation produces anxiety-like behaviors and changes PSD-95 levels in the
      forebrain.
AB  - Isolation rearing induces profound behavioral and neurochemical abnormalities in
      rodents. However there have been many controversies with its anxiogenic-like
      effects using models like elevated-plus maze. In the current study we aimed to
      address this by using one novelty-based anxiety paradigm that has been largely
      overlooked in previous isolation rearing studies. We found that eight-week
      isolation rearing produced potent anxiogenic-like effects in novelty-induced
      hypophagia test in mice. We also demonstrated PSD-95 levels were elevated in the
      hippocampus and amygdala and reduced in the frontal cortex after social
      isolation. This study provides further behavioral and neurochemical evidence to
      support that isolation rearing can produce anxiogenic-like effects in rodents.

PMID- 22387066
TI  - Screening for FMR1 expanded alleles in patients with parkinsonism in mainland
      China.
AB  - Expanded alleles of the fragile X mental retardation 1 (FMR1) gene are generally
      divided into four classes based on the abundance of unstable CGG repeat
      expansions (CGGs) in its 5'-untranslated region. It has recently been reported
      that two of the four classes, premutation (55-200 CGGs) and gray zone (GZ, 40-54
      CGGs) alleles, was potentially associated with parkinsonism. To investigate this
      association in patients in mainland China, a total of 360 Chinese patients with
      parkinsonism and 295 gender and age matched controls were recruited in this
      study. Indeed, no premutation or full mutation alleles (>200 CGGs) was detected
      among all the subjects. A total of 11 patients with parkinsonism were identified
      to have GZ alleles compared with only 1 carrier among the controls (P<0.05).
      Notably, 10 of the 11 GZ alleles carriers with parkinsonism were female, which
      was 6.8% of all 147 female patients compared with none in the control females
      (P<0.05). No significant difference was detected between the male groups of
      patients and controls. Therefore, our results indicate that FMR1 GZ allele is
      potentially associated with parkinsonism in mainland China, and the association
      is only present in the female patients, but not in the male.

PMID- 22387067
TI  - Intranasal delivery of siRNA to the olfactory bulbs of mice via the olfactory
      nerve pathway.
AB  - Adopting RNAi technology for targeted manipulation of gene expression in the
      central nervous system (CNS) will require delivery of RNAi constructs to the CNS
      followed by cellular transfection and induction of the RNAi machinery.
      Significant strides have been made in enhancing RNAi transfection and tailoring
      knockdown toward specific gene targets, however, delivery of the RNAi constructs
      to the CNS remains a significant challenge. One possible solution for targeting
      siRNA to the CNS is intranasal administration, which noninvasively delivers a
      variety of compounds to the CNS. The current study examined delivery of
      fluorescently labeled siRNA from the nasal cavity to the olfactory bulbs via the
      olfactory nerve pathway. siRNA was observed along the length of the olfactory
      nerve bundles, from the olfactory mucosa of the nasal cavity to the anterior
      regions of the olfactory bulbs. In the olfactory mucosa, labeled siRNA was found
      within the olfactory epithelium, Bowman's glands, and associated with blood
      vessels and bundles of olfactory nerves. In the olfactory bulbs, siRNA was
      observed in the olfactory nerve, glomerular and mitral cell layers. These results
      demonstrate a role of the olfactory nerve pathway in targeting siRNA to the
      olfactory bulbs. Additional investigations will be required to assess the
      distribution of intranasal siRNA to additional regions of the brain and explore
      the capacity of the delivered siRNA to silence gene expression in the CNS.

PMID- 22387068
TI  - Interleukin 1 receptor contributes to methamphetamine- and sleep deprivation
      induced hypersomnolence.
AB  - Methamphetamine-induced wakefulness is dependent on monoamine transporter
      blockade. Subsequent to methamphetamine-induced wakefulness, the amount of time
      spent asleep and the depth of sleep are increased relative to baseline sleep. The
      mechanisms that drive methamphetamine-induced hypersomnolence are not fully
      understood. We recently observed that methamphetamine exposure elevates the
      expression of the sleep-promoting cytokine, interleukin-1beta in CD11b-positive
      monocytes within the brain. Here, we sought to determine whether activation of
      the interleukin 1 receptor (IL1R) drives the increase in the depth and amount of
      sleep that occurs subsequent to methamphetamine-induced wakefulness. IL1R
      deficient mice and wild type control mice were subjected to systemic
      methamphetamine (1 and 2mg/kg) and saline treatments. The wake-promoting effect
      of methamphetamine was modestly potentiated by IL1R-deficiency. Additionally, the
      increase in time spent in NREMS subsequent to methamphetamine-induced wakefulness
      in wild type mice was abolished in IL1R-deficient mice. The increase in time
      spent asleep after 3h of behaviorally enforced wakefulness was also abolished in
      IL1R-deficient mice. Increases in EEG slow wave activity triggered by
      methamphetamine and sleep deprivation were of equal magnitude in IL1R-deficient
      and wild type mice. These data demonstrate that IL1R activation contributes to
      hypersomnolence that occurs after sleep loss, whether that sleep loss is
      triggered pharmacologically by methamphetamine or through behavioral sleep
      deprivation.

PMID- 22387069
TI  - SKF 38393 reverses cocaine-conditioned place preference in mice.
AB  - Cocaine is a psychotropic drug with a high potential for abuse due to its
      euphoric effects. Efforts to develop medications for the treatment of cocaine
      dependence have not been clinically successful. Some studies using animal models
      have shown positive effects of dopaminergic agents such as partial agonists of
      the dopamine D1 receptor. Thus, this study aimed to examine the effect of the
      dopamine D1 receptor partial agonist SKF 38393 on cocaine craving. Adult male
      C57BL/6J mice were injected with cocaine for 10 days in a conditioned place
      preference apparatus using a biased procedure and subsequently treated for three
      consecutive days with SKF 38393. The results showed that SKF 38393 was able to
      block the preference of cocaine-conditioned animals for the compartment paired
      with the drug without showing effects on locomotor activity. The results of this
      study suggest that partial activation of D1 dopamine receptors may be necessary
      for the development of pharmacotherapies for cocaine addiction.

PMID- 22387070
TI  - Association of mutations in the glucocerebrosidase gene with Parkinson disease in
      a Korean population.
AB  - Recent studies have shown an association between Parkinson disease (PD) and
      mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA),
      which is deficient in patients with Gaucher disease. In Asian populations, 2
      mutational analysis studies have been performed in all exons of GBA; one study in
      a Japanese population showed the highest odds ratio among all ethnic groups,
      whereas the other study in ethnic Chinese observed a trend of a higher frequency
      of GBA mutation in PD patients without statistical significance. To investigate
      whether there is an association between PD and mutations of GBA in a Korean
      population, we analyzed mutations of GBA and compared mutation frequencies
      between Korean PD patients and a control population. We analyzed mutations in GBA
      by sequencing exons of GBA in 277 Korean PD patients and 291 control subjects.
      All exons of GBA were sequenced in all PD cases and 100 control subjects. Exon 2
      and exons 5-11, where mutations of GBA were found in our PD patients, were
      analyzed in an additional 191 control subjects. Five different pathogenic
      heterozygous GBA mutations, including N188S, P201H, R257Q, S271G, and L444P, were
      identified in 9 PD cases (3.2%), whereas there were no GBA mutations found in
      control subjects (p<0.01, OR 20.6, 95% CI 1.2-356.4). The mean age-at-onset of
      heterozygous GBA variants carriers was younger than that of non-carriers (48.6+/
      11.9 versus 57.9+/-13.5, p<0.05, Mann-Whitney test). Our results suggest that
      heterozygous mutations of GBA represent a risk factor for PD in Koreans.

PMID- 22387071
TI  - A practical model of osteomyelitis-induced bone pain by intra-tibial injection of
      Staphylococcus aureus in rats.
AB  - Osteomyelitis is an acute or chronic inflammatory process of bone accompanied
      with mild to severe pain. Generally, mild to moderate pain induced by
      osteomyelitis can be relieved, yet severe pain cannot. Therefore, a further
      investigation into the mechanism of severe pain induced by osteomyelitis is
      needed. In this study, a traditional rat model of osteomyelitis was induced by
      intra-tibial injection of Staphylococcus aureus. Then, a series of tests
      including bone histology, blood analysis, mechanical allodynia, thermal
      hyperalgesia, and immunohistochemistry were performed. Four days after an intra
      tibial bacterial injection, acute inflammation was observed in the bone marrow,
      which developed into chronic inflammation 12 days after the procedure. The
      results from the blood analysis confirmed the existence of bone inflammation.
      Significant mechanical allodynia and thermal hyperalgesia developed shortly after
      the injection. This osteomyelitis-induced pain behavior was reversed by
      Celecoxib, a selective COX-2 inhibitor. Furthermore, significant increase of both
      microglia and astrocytes was observed in the spinal cord. Our results suggest
      that osteomyelitis-induced rats display pain related behaviors and associated
      neurochemical changes. This study thus provides a novel practical rat model of
      bone inflammation induced pain.

PMID- 22387072
TI  - Calcium-induced changes in calmodulin structural dynamics and thermodynamics.
AB  - The thermodynamics of the interaction between Ca(2+) and calmodulin (CaM) was
      examined using isothermal titration calorimetry (ITC). The chemical denaturation
      of calmodulin was monitored spectroscopically to determine the stability of
      Ca(2+)-free (apo) and Ca(2+)-loaded (holo) CaMs. We explored the conformational
      and structural dynamics of CaM using amide hydrogen-deuterium (H-D) exchange
      coupled with Fourier transform infrared (FT-IR) spectroscopy. The results of H-D
      exchange and FT-IR suggest that CaM activation by Ca(2+) binding involves
      significant conformational changes. The results have also revealed that while the
      overall conformation of holo-CaM is more stable than that of the apo-CaM, some
      part of its alpha-helix structures, most likely the EF-hand domain region, has
      more solvent exposure, thus, has a faster H-D exchange rate than that of the apo
      CaM. The ITC method provides a new strategy for obtaining site-specific Ca(2+)
      binding properties and a better estimation of the cooperativity and
      conformational change contributions of coupled EF-hand proteins.

PMID- 22387074
TI  - Therapeutic targeting of interleukin-6 trans-signaling does not affect the
      outcome of experimental tuberculosis.
AB  - Treatment of autoreactive inflammatory diseases such as rheumatoid arthritis with
      anti-inflammatory drugs is associated with an increased rate of reactivation
      tuberculosis (TB). Interleukin-6 (IL-6) plays a pivotal role in inflammation and
      protection against various infectious diseases. IL-6 signals by two mechanisms
      via the ubiquitous transmembrane protein gp130: 'classic' signaling using the
      membrane-bound IL-6 receptor (IL-6R), which is expressed mainly on hepatocytes
      and some leukocytes, and trans-signaling using soluble IL-6R (sIL-6R). Trans
      signaling by the IL-6/sIL-6R complex is selectively inhibited by natural soluble
      gp130 (sgp130) and by sgp130 designer proteins. As specific blockade of IL-6
      trans-signaling represents a promising approach for the therapy of inflammatory
      diseases, we evaluated the potential risk of interfering with this alternative
      pathway and analyzed the outcome of experimental TB after treatment with an IgG1
      Fc fusion protein of soluble gp130 (sgp130Fc) and in sgp130Fc-overexpressing
      transgenic (sgp130Fc(tg)) mice. In contrast to treatment with anti-tumor necrosis
      factor (TNF) antibodies, administration of sgp130Fc did not interfere with
      protective immune responses after infection with Mycobacterium tuberculosis
      (Mtb). Moreover, Mtb-infected sgp130Fc(tg) mice were capable of controlling
      mycobacterial growth. Our finding that IL-6 trans-signaling plays no role for
      protective immune responses against Mtb supports the superior safety of
      therapeutic targeting of IL-6 trans-signaling compared to anti-TNF treatment.

PMID- 22387073
TI  - Impaired phagocytic capacity driven by downregulation of major phagocytosis
      related cell surface molecules elicits an overall modulatory cytokine profile in
      neutrophils and monocytes from the indeterminate clinical form of Chagas disease.
AB  - The distinct ability of phagocytes to present antigens, produce cytokines and
      provide co-stimulatory signals may contribute to the severity of the outcome of
      Chagas disease. In this paper, we evaluate the phenotypic features of phagocytes
      along with the cytokine signature of circulating T-cells from Chagas disease
      patients with indeterminate (IND) and cardiac (CARD) clinical forms of the
      disease. Our data demonstrated that neutrophils from IND patients displayed an
      impaired ability to produce cytokines. A lower Trypanosoma cruzi phagocytic index
      and higher nitric oxide levels were characteristics of monocytes from IND. The
      impaired phagocytic capacity did not reflect on the levels of anti-T. cruzi IgG,
      but was detectable in the downregulation of Fc-gammaR, TLR and CR1 molecules. The
      monocyte-derived cytokine signature demonstrated that a down-regulated synthesis
      of IL-12 and a modulatory state were evidenced by a positive correlation between
      IL-12 and IL-10 with a lower synthesis of TNF-alpha. The down-regulation of MHC
      II and CD86 in monocytes supports the occurrence of particularities in the APC
      activation-arm in IND, and may be involved in the T-cell pro-inflammatory pattern
      counterbalanced by a potent IL-10 response. Our findings support the hypothesis
      that differential phenotypic features of monocytes from IND may be committed to
      the induction of a distinct immune response related to low morbidity in chronic
      Chagas disease.

PMID- 22387075
TI  - Ability of antibodies specific to the HIV-1 envelope glycoprotein to block the
      fusion inhibitor T20 in a cell-cell fusion assay.
AB  - The anti-HIV peptide T20 is able to inhibit the syncytia formation between CHO-WT
      and HeLa CD4(+)cells. We found that several sera of HIV-infected patients have
      the capacity to block the inhibition of fusion by T20. Suggesting that these sera
      may contain antibody which can block T20 access and prevent membrane fusion, we
      studied the ability of a panel of antibodies directed to different regions of HIV
      1 envelope glycoprotein to block the inhibition of fusion by T20. We found that
      the C1 and V3 loop regions of gp120 and the heptad repeat 1, the immunodominant C
      C region and the Kennedy epitope of gp41 located in the intracytoplasmic tail
      were the target for antibodies capable to block the inhibition of syncytia
      formation by T20. We suggest that these antibodies have the capacity to
      counteract the anti-fusion effect of T20 by preventing its binding to the
      interaction sites. Further studies are needed to determine if some of them
      recognize new T20 interaction sites.

PMID- 22387076
TI  - GTP binds to alpha-crystallin and causes a significant conformational change.
AB  - ATP was previously reported to bind to the chaperone alpha-crystallin resulting
      in a significant effect on the protein's ability to suppress the aggregation of a
      thermally denatured protein. Here, we have investigated the binding of GTP to
      alpha-crystallin. Unlike ATP, binding of GTP to alpha-crystallin did not affect
      its ability to suppress the aggregation of thermally denatured rhodanese. GTP
      binding induced a conformational change on alpha-crystallin, however the degree
      of exposed hydrophobic surfaces, which are believed to be involved in the binding
      of the chaperone to denaturing proteins did not change. Here, we report that GTP
      binds to alpha-crystallin and this results in a decreased stability of the
      chaperone as indicated by urea denaturation.

PMID- 22387077
TI  - Use of near-infrared spectroscopy in combination with monitoring of external
      jugular vein pressure for early detection of cerebral ischemia by unintentional
      superior vena cava obstruction.

PMID- 22387078
TI  - What is the optimal practice of analgesia for post-thoracotomy pain?

PMID- 22387079
TI  - Pump flow changes do not impair sublingual microcirculation during
      cardiopulmonary bypass.
AB  - OBJECTIVE: The flow rate of the cardiopulmonary bypass (CPB) pump used in cardiac
      surgery often undergoes inherent fluctuations ranging from 10% to 20% of its
      theoretic value. However, the effects of such alterations remain unknown. In the
      present study, the authors investigated whether such variations could induce
      changes in the microvascular flow, which is considered a primary indicator of
      poor perfusion. DESIGN: A prospective, observational, clinical study. SETTING: A
      university-affiliated teaching hospital. PARTICIPANTS: Thirty adult patients
      undergoing elective cardiac surgery with CPB. INTERVENTIONS: Analysis of the
      sublingual microcirculation during CPB using a pump flow rate of 80% or 100% of
      the theoretic value. MEASUREMENTS AND MAIN RESULTS: Sidestream dark field (SDF)
      imaging was used to record 2 video clips of the sublingual microcirculation in
      each patient. The videos were recorded at the same site at 80% and 100% of the
      theoretic flow rate. Microvascular analysis displaying the De Backer score, the
      microvascular flow index, the total vessel density, the perfused vessel density,
      and the proportion of perfused vessels was performed. Moreover, the mean arterial
      pressure (MAP), SvO(2), and PaCO(2) were evaluated. No significant changes in the
      measured parameters were noted at the 2 different flow rates. CONCLUSIONS:
      Changes in the CPB pump flow rate within 20% (80%-100%) of its theoretic value do
      not alter the sublingual microcirculation. Thereafter, it is conceivable that
      during perioperative adjustments of the CPB pump rate, blood flow autoregulation
      mechanisms are activated so that limited changes in the pump flow can be
      considered safe not only at the sublingual site but also for the entire
      microcirculation.

PMID- 22387081
TI  - Severe tricuspid valve regurgitation: a case for laminar flow.

PMID- 22387082
TI  - Prognostic power of pre- and postoperative B-type natriuretic peptide levels in
      patients undergoing abdominal aortic surgery.
AB  - OBJECTIVES: The first aim of the present study was to evaluate the pre- and
      postoperative B-type natriuretic peptide (BNP) levels in patients undergoing
      surgery for repair of an infrarenal abdominal aortic aneurysm (AAA) and analyze
      their power as a predictor of in-hospital cardiac events. The second aim was to
      evaluate the association among pre- and postoperative BNP levels, postoperative
      patient complications, and length of hospital stay. DESIGN: Prospective
      observational study. SETTING: A university hospital. PARTICIPANTS: Forty-five
      patients undergoing elective surgery for an abdominal aortic aneurysm.
      INTERVENTIONS: The plasma BNP level was assessed just before surgery and then on
      postoperative day 1. Cardiac troponin I levels were measured postoperatively on
      arrival to the intensive care unit (time 0) and then 12, 48, and 72 hours later.
      MEASUREMENTS AND MAIN RESULTS: The preoperative BNP concentration in patients who
      developed an acute myocardial infarction was 209 (IQR 84-346) pg/mL compared with
      74 (IQR 28-142) pg/mL in those who did not. The difference between groups was
      statistically significant (p = 0.04). The Spearman correlation showed that
      postoperative BNP levels correlated significantly with preoperative BNP levels (r
      = 0.73, p = 0.0001), length of hospital stay (r = 0.35, p = 0.04), and troponin I
      concentration at 0 hour (r = 0.42, p = 0.02), 12 hours (r = 0.51, p = 0.0052),
      and 48 hours (r = 0.40, p = 0.033). In contrast, preoperative BNP levels
      correlated with troponin I at only 12 hours (r = 0.34, p = 0.02). Postoperative
      BNP levels were influenced significantly by transfusions (p = 0.035) and cross
      clamping times (p = 0.038). CONCLUSIONS: The present results confirm the high
      negative predictive value of preoperative BNP levels; and postoperative BNP
      levels showed a better correlation with postoperative troponin levels, blood
      transfusion, and postoperative cardiac events.

PMID- 22387083
TI  - A combined strategy improves the solubility of aggregation-prone single-chain
      variable fragment antibodies.
AB  - Recombinant single-chain variable fragment (scFv) antibodies have wide
      applications in the areas of biotechnology and medicine. However, there is
      currently no universal expression-purification system for generating different
      soluble scFvs. In this study, A15 and E34, two genes coding scFvs against human
      IL-17A, were fused with N-terminal signal peptide sequences pelB or STII, or with
      highly hydrophilic tags Trx, NusA, or MBP, respectively. These constructs were
      expressed in Escherichia coli. We found that the scFvs fused with either NusA or
      MBP showed a higher solubility than fused with signal peptides or Trx. The scFvs
      were aggregated when the NusA or MBP was removed by thrombin. Interestingly, we
      observed a reduction of precipitation when the fusion proteins were expressed in
      Origami B(DE3)pLysS cells but not in BL21(DE3)pLysS. Because cleaving the tags
      resulted in the aggregation of scFvs, several solubility-enhancing additives were
      added in the digestion buffer and only L-arginine (Arg) or Tween20 promoted the
      solubility. After an affinity chromatography, the scFvs were separated from the
      tags with the purity up to 90%. The final yield of scFvs from the scFv-MBP system
      was approximately 8.9 mg/L of culture medium and 1.5 mg/g of wet weight cells,
      which was 1.6-fold higher than the yield from the scFv-NusA system. The obtained
      scFvs exhibited normal binding affinities and activities after endotoxin removal.
      In conclusion, we describe a strategy combining the fusion tags, the Escherichia
      coli with oxidizing bacterial cytoplasm, and the solubility-enhancing additives
      for expressing and purifying the soluble and functional scFvs.

PMID- 22387084
TI  - Does this patient with minor head trauma need neuroimaging?

PMID- 22387085
TI  - Hyperthermia and multiorgan failure after abuse of "bath salts" containing 3,4
      methylenedioxypyrovalerone.
AB  - "Bath salts" are being increasingly used as drugs of abuse. These products have
      been found to contain a variety of compounds, including 3,4
      methylenedioxypyrovalerone (MDPV). We present a case of a 25-year-old man who
      injected bath salts and acutely developed severe agitation, hyperthermia, and
      tachycardia. Despite aggressive early medical management, including dialysis, he
      progressed to multiorgan system failure, although he ultimately recovered after a
      prolonged hospital course. The only chemical substance detected on comprehensive
      toxicologic testing was MDPV, a synthetic cathinone analogue. According to our
      case, MDPV abuse may result in adverse multisystem organ effects, including
      rhabdomyolysis, cardiac injury, hepatic injury, and renal failure. It is unknown
      whether these end-organ effects were due to direct cellular toxicity induced by
      MDPV or a result of the patient's marked agitation and hyperthermia. Acute
      management should focus on the rapid identification of organ injury and
      appropriate supportive care.

PMID- 22387086
TI  - Hydroxocobalamin versus sodium thiosulfate for the treatment of acute cyanide
      toxicity in a swine (Sus scrofa) model.
AB  - STUDY OBJECTIVE: We compare the efficacy of hydroxocobalamin to sodium
      thiosulfate to reverse the depressive effects on mean arterial pressure in a
      swine model of acute cyanide toxicity and gain a better understanding of the
      mechanism of action of the hydroxocobalamin in reversal of the toxicity. METHODS:
      Swine were intubated, anesthetized, and instrumented with central arterial and
      venous lines and a pulmonary artery catheter. Animals (n=36) were randomly
      assigned to one of 3 groups: hydroxocobalamin alone (150 mg/kg), sodium
      thiosulfate alone (413 mg/kg), or hydroxocobalamin (150 mg/kg)+sodium thiosulfate
      (413 mg/kg) and monitored for 60 minutes after the start of antidotal infusion.
      Cyanide was infused until severe hypotension developed, defined as blood pressure
      50% of baseline mean arterial pressure. Repeated-measures ANOVA was used to
      determine statistically significant changes between groups over time. RESULTS:
      Time to hypotension (25, 28, and 33 minutes), cyanide dose at hypotension (4.7,
      5.0, and 5.6 mg/kg), and mean cyanide blood levels (3.2, 3.7, and 3.8 MUg/mL) and
      lactate levels (7, 8.2, 8.3 and mmol/L) were similar. All 12 animals in the
      sodium thiosulfate group died compared with 2 of 12 in the
      hydroxocobalamin/sodium thiosulfate group and 1 of 12 in hydroxocobalamin group.
      No statistically significant differences were detected between the
      hydroxocobalamin and hydroxocobalamin/sodium thiosulfate groups for carbon
      monoxide, mean arterial pressure, cyanide levels, or mortality at 60 minutes.
      Lactate level (2.6 versus 2.1 mmol/L), pH (7.44 versus 7.42), and bicarbonate
      level (25 versus 26 mEq/L) at 60 minutes were also similar between groups.
      CONCLUSION: Sodium thiosulfate failed to reverse cyanide-induced shock in our
      swine model of severe cyanide toxicity. Further, sodium thiosulfate was not found
      to be effective when added to hydroxocobalamin in the treatment of cyanide
      induced shock. Hydroxocobalamin alone was again found to be effective for severe
      cyanide toxicity.

PMID- 22387087
TI  - Does diffusion-weighted imaging predict short-term risk of stroke in emergency
      department patients with transient ischemic attack?
AB  - STUDY OBJECTIVE: The optimal diagnostic evaluation for establishing the risk of
      stroke among patients presenting to the emergency department (ED) with a
      transient ischemic attack has not been determined. The objective of this review
      is to assess the ability of diffusion-weighted magnetic resonance imaging (MRI)
      to predict the short-term risk of stroke. METHODS: MEDLINE, EMBASE, and the
      Cochrane Library were queried to identify studies examining the use of diffusion
      weighted MRI in patients with classically defined transient ischemic attack. The
      primary outcome measure was the rate of stroke at 48 hours. Two reviewers
      determined study eligibility and extracted data. Quality was assessed according
      to published recommendations for the design and reporting of prognostic studies.
      RESULTS: One thousand six hundred ninety-six abstracts were identified and 35
      articles underwent full-text review. Six cohort studies met the inclusion
      criteria but were limited by selection bias and differences in duration and
      completeness of follow-up. Results were not consistent across studies, with 5
      reporting higher rates of stroke among diffusion-weighted MRI-positive patients,
      whereas 1 study reported higher rates in diffusion-weighted MRI-negative
      patients. Among the 4 studies (N=629 patients) reporting 48-hour outcomes, the
      risk of stroke ranged from 0% to 2.9% in patients with negative diffusion
      weighted MRI findings compared with 0% to 9% among those with positive diffusion
      weighted MRI results. CONCLUSION: Studies of variable quality, consistency, and
      precision suggest that diffusion-weighted MRI may identify patients at
      sufficiently low risk to warrant ED discharge and close outpatient follow-up.

PMID- 22387088
TI  - Extremity fracture pain after emergency department reduction and casting:
      predictors of pain after discharge.
AB  - STUDY OBJECTIVE: The aims of this study are to determine the prevalence of
      pediatric extremity fracture pain after emergency department (ED) discharge,
      compare pain severity between fractures requiring simple casting versus sedated
      reduction and casting, and explore predictors of postdischarge pain. METHODS:
      This is a prospective observational study of children aged 4 to younger than 18
      years and presenting to the ED with extremity fracture from May 2010 to February
      2011. The Parents' Postoperative Pain Measure, which scores pain according to 15
      behavior-related questions, was completed 48 to 72 hours after discharge. A score
      greater than or equal to 6 of 15 indicates clinically meaningful pain. Univariate
      tests and multivariable regression analyses were used to compare Parents'
      Postoperative Pain Measure scores between cohorts. RESULTS: Two hundred fifty
      seven patients were enrolled; 202 (79%) had Parents' Postoperative Pain Measure
      scores for analysis. Pain scores greater than or equal to 6 were reported by 37
      of 102 (36%) of the simple casted and 44 of 100 (44%) of the reduced casted
      children. There was no difference in scores between the simple (median 4.0) and
      reduced casted (median 5.0) cohorts (difference 16.7%; 95% confidence interval
      [CI] -3.0% to 40%). In the multivariate analysis, ED narcotic administration was
      associated with 24% higher Parents' Postoperative Pain Measure scores (95% CI
      0.95% to 53.6%). Children receiving ED narcotics had more than 2 times increased
      odds of pain scores greater than or equal to 6 after discharge (95% CI 1.24 to
      5.39). CONCLUSION: Children in both simple casted and reduced casted groups had
      clinically meaningful pain after ED discharge. Identifying these children is
      important to improving pain management and discharge care.

PMID- 22387090
TI  - Chlorantholides A-F, eudesmane-type sesquiterpene lactones from Chloranthus
      elatior.
AB  - Six eudesmane-type sesquiterpene lactones, named chlorantholides A-F, were
      isolated from the ethanol extract of Chloranthus elatior (Chloranthaceae)
      together with 12 known compounds. Their structures were elucidated on the basis
      of extensive spectroscopic analysis, and their absolute configurations were
      studied by the CD exciton chirality method. The structure of a recently reported
      eudesmanolide from Chloranthus anhuiensis: 8beta-hydroxy-1-oxoeudesma-3,7(11)
      dien-12,8-olide, was also revised as 8beta-hydroxy-2-oxoeudesma-3,7(11)-dien-12,8
      olide (chlorantholide D).

PMID- 22387089
TI  - Evidence from the scene: paramedic perspectives on involvement in out-of-hospital
      research.
AB  - STUDY OBJECTIVE: In the context of calls to develop better systems for out-of
      hospital clinical research, we seek to understand paramedics' perceptions of
      involvement in research and the barriers and facilitators to that involvement.
      METHODS: This was a qualitative study using semistructured focus groups with 58
      United Kingdom paramedics and interviews with 30 US firefighter-paramedics. The
      study focused on out-of-hospital research (trials of out-of-hospital treatment
      for stroke), whereby paramedics identified potential study subjects or obtained
      consent and administered study treatment in the field. Data were analyzed with a
      thematic and discourse approach. RESULTS: Three key themes emerged as significant
      facilitators and barriers to paramedic involvement in research: patient benefit,
      professional identity and responsibility, and time. Paramedics showed willingness
      and capacity to engage in research but also some reticence because of the
      perceived sacrifice of autonomy and challenge to their identity. Paramedics work
      in a time-sensitive environment and were concerned that research would increase
      time taken in the field. CONCLUSION: Awareness of these perspectives will help
      with development of out-of-hospital research protocols and potentially facilitate
      greater participation.

PMID- 22387091
TI  - Evidence-based use of statins for primary prevention of cardiovascular disease.
AB  - Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as
      statins, are widely available, inexpensive, and represent a potent therapy for
      treating elevated cholesterol. Current national guidelines put forth by the Adult
      Treatment Panel III recommend statins as part of a comprehensive primary
      prevention strategy for patients with elevated low-density lipoprotein
      cholesterol at increased risk for developing coronary heart disease within 10
      years. Lack of a clear-cut mortality benefit in primary prevention has caused
      some to question the use of statins for patients without known coronary heart
      disease. On review of the literature, we conclude that current data support only
      a modest mortality benefit for statin primary prevention when assessed in the
      short term (<5 years). Of note, statin primary prevention results in a
      significant decrease in cardiovascular morbidity over the short and long term and
      a trend toward increased reduction in mortality over the long term. When
      appraised together, these data provide compelling evidence to support the use of
      statins for primary prevention in patients with risk factors for developing
      coronary heart disease over the next 10 years.

PMID- 22387092
TI  - Serotonin depletion of supramammillary/posterior hypothalamus nuclei produces
      place learning deficiencies and alters the concomitant hippocampal theta activity
      in rats.
AB  - Hippocampal theta activity is important for the acquisition of spatial
      information and is strongly influenced and regulated by extra-hippocampal inputs
      from the synchronising ascending system (SAS), which includes the supramammillary
      nucleus (SUMn) and the posterior hypothalamic nucleus (PHn). Together these
      nuclei play an important role in controlling the frequency encoding of theta
      activity and are innervated by serotonin synapses, which also regulate theta
      activity and learning abilities. The participation of the SUMn in place learning
      and modulation of hippocampal theta activity were recently shown; thus, we
      questioned whether serotonin acting on SUMn/PHn could modulate place learning
      ability and concurrent hippocampal theta activity. The serotonergic terminals of
      the SUMn/PHn in rats were lesioned through 5,7-dihydroxytryptamine (5,7-DHT)
      infusion, and hippocampal theta activity during the Morris water maze test was
      recorded. Rats in the vehicle group learned the task efficiently and showed
      learning-related theta changes in the CA1 and dentate gyrus regions throughout
      the training. The 5-HT-depleted rats were deficient in the Morris water maze task
      and showed theta activity in the CA1 and dentate gyrus that were unrelated to the
      processing of learning. We conclude that serotonin can regulate the hippocampal
      theta activity acting on the SUMn/PHn relay of the SAS and that the influence of
      5-HT in these nuclei is required for the learning-related changes in hippocampal
      theta activity that underlie the successful resolution of the Morris water maze
      task.

PMID- 22387093
TI  - In vitro activity of cepharanthine hydrochloride against clinical wild-type and
      lamivudine-resistant hepatitis B virus isolates.
AB  - Hepatitis B virus (HBV) infection causes major public health problems worldwide.
      The clinical limitation of current antiviral drugs for HBV, such as lamivudine,
      is the emergence of drug-resistant viral strains during prolonged antiviral
      therapy. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound,
      has been reported to possess potent activity against various viruses. The present
      study was performed to evaluate the in vitro activity of CH against clinical wild
      type and lamivudine-resistant HBV isolates in transiently transfected cells. HBV
      DNA was extracted from serum samples collected both before lamivudine therapy and
      at the time of viral breakthrough and was amplified by polymerase chain reaction
      (PCR). The amplicons were cloned into a novel expression vector, pHY106, which
      can initiate the intracellular HBV replication cycle after cell transfection.
      Following transfection of the cloned amplicon into HepG2 cells, a drug
      susceptibility assay was performed. The level of viral antigen, HBeAg, was
      determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time
      PCR (Q-PCR) was used for determining the amount of intracellular HBV DNA. Heat
      stress cognate 70 (Hsc70), a host protein required for HBV replication, was also
      analyzed by reverse transcription PCR (RT-PCR) to explore the possible antiviral
      mechanism of CH. The results showed that CH inhibited replication and HBeAg
      production by either wild-type or lamivudine-resistant HBV clinical isolates in a
      dose-dependent manner. The Hsc70 mRNA was also downregulated significantly. In
      conclusion, CH is active against both wild-type and lamivudine-resistant HBV
      clinical isolates, and its activity may be associated with its inhibition of host
      Hsc70.

PMID- 22387094
TI  - Arctigenin suppresses receptor activator of nuclear factor kappaB ligand (RANKL)
      mediated osteoclast differentiation in bone marrow-derived macrophages.
AB  - Osteoclasts, multinucleated bone-resorbing cells, are closely associated with
      bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are
      derived from hematopoietic precursor cells, and their differentiation is mediated
      by two cytokines, including macrophage colony stimulating factor and receptor
      activator of nuclear factor kappaB ligand (RANKL). Previous studies have shown
      that arctigenin exhibits an anti-inflammatory effect. However, the effect of
      arctigenin on osteoclast differentiation is yet to be elucidated. In this study,
      we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in
      bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated
      bone resorption. Additionally, the expression of typical marker proteins, such as
      NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited.
      Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a
      dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor
      tyrosine-based activation motif-mediated costimulatory signaling molecules,
      including Syk and PLCgamma2, and Gab2. Notably, arctigenin inhibited the
      activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented
      osteoclast differentiation in the calvarial bone of mice following stimulation
      with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast
      differentiation in vitro and in vivo. Therefore, arctigenin may be useful for
      treating rheumatoid arthritis and osteoporosis.

PMID- 22387095
TI  - Afferent drive elicits ongoing pain in a model of advanced osteoarthritis.
AB  - Osteoarthritis (OA) is a chronic condition characterized by pain during joint
      movement. Additionally, patients with advanced disease experience pain at rest
      (ie, ongoing pain) that is generally resistant to nonsteroidal antiinflammatory
      drugs. Injection of monosodium iodoacetate (MIA) into the intraarticular space of
      the rodent knee is a well-established model of OA that elicits weight-bearing
      asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain
      is present in this model is unknown. Additionally, the possible relationship of
      ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint
      osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg).
      However, only rats treated with the highest dose of MIA showed conditioned place
      preference to a context paired with intraarticular lidocaine, indicating relief
      from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed
      to block MIA-induced ongoing pain. Systemic AMG9810, a transient receptor
      potential V1 channel (TRPV1) antagonist, effectively blocked thermal
      hypersensitivity, but failed to block high-dose MIA-induced weight asymmetry or
      ongoing pain. Additionally, systemic or intraarticular HC030031, a TRPA1
      antagonist, failed to block high-dose MIA-induced weight asymmetry or ongoing
      pain. Our studies suggest that a high dose of intraarticular MIA induces ongoing
      pain originating from the site of injury that is dependent on afferent fiber
      activity but apparently independent of TRPV1 or TRPA1 activation. Identification
      of mechanisms driving ongoing pain may enable development of improved treatments
      for patients with severe OA pain and diminish the need for joint replacement
      surgery.

PMID- 22387096
TI  - Changes in regional gray matter volume in women with chronic pelvic pain: a voxel
      based morphometry study.
AB  - Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to
      affect 15%-20% of women in the United States. Endometriosis is often associated
      with CPP, however, other factors, such as preexisting or concomitant changes of
      the central pain system, might contribute to the development of chronic pain. We
      applied voxel-based morphometry to determine whether women with CPP with and
      without endometriosis display changes in brain morphology in regions known to be
      involved in pain processing. Four subgroups of women participated: 17 with
      endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without
      endometriosis, and 23 healthy controls. All patients with endometriosis and/or
      CPP were surgically confirmed. Relative to controls, women with endometriosis
      associated CPP displayed decreased gray matter volume in brain regions involved
      in pain perception, including the left thalamus, left cingulate gyrus, right
      putamen, and right insula. Women with CPP without endometriosis also showed
      decreases in gray matter volume in the left thalamus. Such decreases were not
      observed in patients with endometriosis who had no CPP. We conclude that CPP is
      associated with changes in regional gray matter volume within the central pain
      system. Although endometriosis may be an important risk factor for the
      development of CPP, acting as a cyclic source of peripheral nociceptive input,
      our data support the notion that changes in the central pain system also play an
      important role in the development of chronic pain, regardless of the presence of
      endometriosis.

PMID- 22387097
TI  - Cancer and sphingolipid storage disease therapy using novel synthetic analogs of
      sphingolipids.
AB  - Sphingolipid metabolites have become recognized for their participation in cell
      functions and signaling events that control a wide array of cellular activities.
      Two main sphingolipids, ceramide and sphingosine-1-phosphate, are involved in
      signaling pathways that regulate cell proliferation, apoptosis, motility,
      differentiation, angiogenesis, stress responses, protein synthesis, carbohydrate
      metabolism, and intracellular trafficking. Ceramide and S1P often exert opposing
      effects on cell survival, ceramide being pro-apoptotic and S1P generally
      promoting cell survival. Therefore, the conversion of one of these metabolites to
      the other by sphingolipid enzymes provides a vast network of regulation and
      provides a useful therapeutic target. Here we provide a survey of the current
      knowledge of the roles of sphingolipid metabolites in cancer and in lipid storage
      disease. We review our attempts to interfere with this network of regulation and
      so provide new treatments for a range of diseases. We synthesized novel analogs
      of sphingolipids which inhibit the hydrolysis of ceramide or its conversion to
      more complex sphingolipids. These analogs caused elevation of ceramide levels,
      leading to apoptosis of a variety of cancer cells. Administration of a synthetic
      analog to tumor-bearing mice resulted in reduction and even disappearance of the
      tumors. Therapies for sphingolipid storage diseases, such as Niemann-Pick and
      Gaucher diseases were achieved by two different strategies: inhibition of the
      biosynthesis of the substrate (substrate reduction therapy) and protection of the
      mutated enzyme (chaperone therapy). Sphingolipid metabolism was monitored by the
      use of novel fluorescent sphingolipid analogs. The results described in this
      review indicate that our synthetic analogs could be developed both as anticancer
      drugs and for the treatment of sphingolipid storage diseases.

PMID- 22387098
TI  - Oxidation and formation of oxidation products of beta-carotene at boiling
      temperature.
AB  - beta-Carotene is one of the most important lipid component extensively used in
      food industries as source of pro-vitamin A and colorant. During processing and
      storage beta-carotene is oxidized and degraded to various oxidation compounds.
      Some of these compounds are also the key aroma compounds in certain flowers,
      vegetables and fruits. The methods for analysis and determination of these
      oxidized products formed during food boiling or preparation are key to the
      understanding the chemistry of these compounds. This paper presents a novel
      analytical method incorporating high performance liquid chromatography with diode
      array and mass spectrometric detection for the characterization of oxidation,
      isomerization and oxidation products of beta-carotene in toluene at boiling
      temperature. HPLC and APCI-MS was optimized using oxidized sample and flow
      injection analysis of the standard beta-carotene respectively. beta-Carotene was
      oxidized in the Rancimat at 110 degrees C for 30, 60 and 90 min. The oxidized
      samples were than analyzed by HPLC system at 450 nm and 350 nm as well as
      scanning and single ion monitoring mass spectrometry. A total of ten oxidation
      products and three Z-isomers were reported. Extensive isomerization was observed
      during treatment at the control accelerated conditions. The oxidation products
      include five apo-carotenals, three diepoxides, one mono-epoxide and one short
      chain species. Results show that the method was reproducible, accurate and
      reliable for the separation and identification of oxidation products of beta
      carotene.

PMID- 22387099
TI  - Cribriform-morular variant of papillary thyroid carcinoma: characteristic
      histologic feature of adenomatous polyposis. A case report.
AB  - We report the case of a 24-year-old woman with familial adenomatous polyposis and
      diagnosed with cribriform-morular variant of papillary thyroid carcinoma. Neck
      ultrasound and computed tomography identified multiple nodules in the thyroid
      gland and neck lymph nodes. The cytological analysis was compatible with the
      diagnosis of papillary cancer of the thyroid. Total thyroidectomy with lymph node
      dissection was performed. The histological analysis established the diagnosis of
      cribriform-morular variant of papillary thyroid carcinoma. Despite preoperative
      findings suggesting an aggressive form of thyroid cancer with lymph node
      involvement, the final diagnosis was a variant of papillary thyroid carcinoma
      often associated with familial adenomatous polyposis and known to have a good
      prognosis.

PMID- 22387100
TI  - Towards synthetic microbial consortia for bioprocessing.
AB  - The use of microbial consortia for bioprocessing has been limited by our ability
      to reliably control community composition and function simultaneously. Recent
      advances in synthetic biology have enabled population-level coordination and
      control of ecosystem stability and dynamics. Further, new experimental and
      computational tools for screening and predicting community behavior have also
      been developed. The integration of synthetic biology with metabolic engineering
      at the community level is vital to our ability to apply system-level approaches
      to building and optimizing synthetic consortia for bioprocessing applications.
      This review details new methods, tools and opportunities that together have the
      potential to enable a new paradigm of bioprocessing using synthetic microbial
      consortia.

PMID- 22387101
TI  - The effects of dynamic changes of malonyl ginsenosides on evaluation and quality
      control of Panax ginseng C.A. Meyer.
AB  - To clarify the effects of malonyl ginsenosides (MGR) on evaluation and quality
      control of Panax ginseng, the contents of neutral and malonyl ginsenosides from
      P. ginseng were examined by high-performance liquid chromatography equipped with
      UV-VIS detector (HPLC-UV) during extraction, processing and storage. Several
      solvents, including water, ethanol, methanol, and n-butanol were used in the cold
      soaked extraction (CSE). Among the four extraction solvents, methanol was found
      to be the most efficient. CSE was compared with other extraction methods such as
      Soxhlet extraction (SE), heat reflux extraction (HRE), ultrasonic-assisted
      extraction (UAE), and microwave-assisted extraction (MAE). The content of MGR
      showed significant differences, higher in CSE and UAE; lower in MAE and HRE; no
      MGR could be detected after SE. However, the total contents of neutral and
      malonyl ginsenosides were not different. Meanwhile, white ginseng, stored at 25
      degrees C in air of low humidity, showed a marked decrease in the concentration
      of MGR from 1.19% to 0.63% but with an increase in the neutral ginsenosides from
      1.12% to 1.53% after 0-9-month storage. The results indicated that MGR changed
      dynamically in P. ginseng with different extraction solvents, extraction methods
      and increasing storage time. The total ginsenosides was not only underestimated
      but also determined imprecisely by ignoring malonyl ginsenosides. On the basis of
      our results, we suggest that malonyl ginsenosides should be transformed into the
      corresponding neutral ginsenosides during sample preparation for quality control
      and evaluation of P. ginseng. Then the content of six neutral ginsenosides in
      samples was used as the true level of total ginsenosides. The results reported
      here might provide useful information for accurate evaluation and quality control
      of P. ginseng.

PMID- 22387102
TI  - Microdialysis combined with liquid chromatography-tandem mass spectrometry for
      the determination of levo-tetrahydropalmatine in the rat striatum.
AB  - Levo-tetrahydropalmatine (l-THP), one of the main active alkaloids isolated from
      Rhizoma corydalis, was recently found to elicit profound effects on the
      dopaminergic system in the striatum, which plays an important role in regulating
      nociception. A rapid and sensitive method based on microdialysis combined with
      liquid chromatography-tandem mass spectrometry was developed for the
      determination of l-THP in the rat striatum. Microdialysis probes were
      stereotactically placed in the striatal hemisphere, and l-THP was measured from
      the microdialysates collected using LC-MS/MS. Reverse-phase LC separation was
      accomplished on a DiamonsilTM C18 column (50 mm * 2.1 mm ID, 5MUm) with the
      mobile phase composed of methanol-water (50:50, v/v) at a flow rate of 0.2
      ml/min. The method had a chromatographic total run time of 5 min. Detection was
      performed in electrospray positive mode and quantification was executed in
      selected reaction monitoring mode. The following transitions were monitored: m/z
      356.0->191.9 for l-THP and 256.0->167.1 for the internal standard
      diphenhydramine. The method was sensitive with a lower limit of quantitation
      (LLOQ) of 0.1 ng/ml for l-THP, with good linearity in the range of 0.1-1000 ng/ml
      (r(2)>=0.999). All the validation data, such as accuracy, precision, and inter
      day repeatability were within the required limits. The method was successfully
      applied to pharmacokinetic study of the l-THP in the rat striatum.

PMID- 22387103
TI  - Nano-TiO(2)-flavin adenine dinucleotide film redox processes in contact to
      humidified gas | salt electrolyte.
AB  - Redox processes in nano-TiO(2)-flavin adenine dinucleotide (TiO(2)-FAD) layer-by
      layer assembled films on ITO substrate electrodes are investigated and compared
      in contact to aqueous electrolyte media (for dilute and saturated electrolyte)
      and in contact to solid humidified salt electrolyte (for extreme salt levels and
      different types of salts). Under these unusual conditions an aqueous microphase
      present at the gas | salt | electrode interface allows voltammograms to be
      obtained and redox processes to be analysed. It is demonstrated that the 2
      electron 2-proton reduction of FAD can be used as reporter redox system to
      determine local pH at the electrode | gas | salt interface as pH 15, 12, 7 for
      contacts to K(3)PO(4), K(2)HPO(4), and KH(2)PO(4), respectively. Exposure to
      gases such as carbon dioxide is shown to lead to unexpected changes in surface
      pH. In the future, bio-electrochemical microphase processes under halophilic
      conditions could be useful for air-quality and rapid gas sensing devices.

PMID- 22387104
TI  - Electrochemical detection of natural DNA damage induced by in situ peroxidase
      generated reactive nitrogen species in DNA layer-by-layer films.
AB  - The NO(2)* radical is one kind of reactive nitrogen species and can be generated
      by horseradish peroxidase (HRP)-catalyzed oxidation of nitrite (NO(2)(-)) in the
      presence of hydrogen peroxide (H(2)O(2)) and may cause DNA damage in living
      system. In the present work, {PDDA/DNA}(4) layer-by-layer (LBL) films assembled
      with poly(diallyldimethylammonium chloride) (PDDA) and natural double-stranded
      DNA on electrodes were used to detect DNA damage induced by NO(2)* radicals
      generated from the HRP+H(2)O(2)+NO(2)(-) incubation system using cyclic
      voltammetry with Ru(bpy)(3)(2+) as the electroactive catalyst in solution. HRP
      and DNA were then further assembled into PDDA/DNA/{HRP/DNA}(2) LBL films, and the
      damage of DNA in the films caused by the NO(2)* radicals produced in situ by
      incubation of the films with H(2)O(2)+NO(2)(-) solutions was detected
      electrochemically. When catalase layers were assembled on the surface of
      PDDA/DNA/{HRP/DNA}(2) films, the DNA damage induced by the H(2)O(2)+NO(2)(-)
      system was inhibited since the catalase in the films could effectively decompose
      H(2)O(2), and the NO(2)* radicals could not be generated. This work not only
      provides a foundation for fabricating electrochemical biosensors in detecting
      NO(2)*-induced DNA damage, but also offers an in vitro model to simulate the
      pathway of DNA damage and protection in living process.

PMID- 22387105
TI  - Polypharmacy with common diseases in hospitalized elderly patients.
AB  - BACKGROUND: Elderly persons are exposed to polypharmacy because of multiple
      chronic conditions. Many risk factors for polypharmacy have been identified
      including age, race/ethnicity, sex, educational achievement level, health status,
      and number of chronic diseases. However, drugs prescribed for individual diseases
      have not been analyzed. OBJECTIVE: The objective of this study was to analyze
      each common disease in the elderly with respect to prescribed drugs and
      polypharmacy. METHODS: A 1-year (January through December 2009) cross-sectional
      study was performed in which all drugs given to hospitalized elderly patients
      (age, >65 years) were investigated. Common diseases of the elderly were separated
      into disease groups including hypertension, hyperlipidemia, gastric ulcer,
      previous stroke, reflux esophagitis, diabetes mellitus, malignancy, osteoporosis,
      angina pectoris, congestive heart failure, chronic obstructive pulmonary disease,
      dementia, and depression. RESULTS: Among 1768 elderly patients, the mean (range)
      age of study patients was 78 (65 to 100) years. The mean (SD) number of diseases
      was 7.7 (3.4), and the number of drugs overall was 4.9 (3.6). The number of drugs
      and prevalence of polypharmacy were hypertension, 5.2 (3.9 [51%]);
      hyperlipidemia, 5.6 (3.8 [58%]); gastric ulcer, 5.4 (3.8 [53%]); previous stroke,
      5.8 (3.2 [61%]); reflux esophagitis, 5.6 (3.8 [40%]), diabetes mellitus, 5.6 (3.1
      [54%]); malignancy, 4.1 (3.1 [37%]); osteoporosis, 5.4 (3.4 [45%]); angina
      pectoris, 5.7 (3.6 [42%]); congestive heart failure, 6.1 (4.0 [60%]); chronic
      obstructive pulmonary disease, 5.0 (3.5 [53%]); dementia, 5.1 (3.2 [52%]); and
      depression, 7.0 (4.2 [73%]). CONCLUSIONS: When assessing the risk of
      polypharmacy, physicians should carefully consider the type of any chronic
      disease. Elderly patients with multiple diseases may be subjected to further
      polypharmacy.

PMID- 22387106
TI  - Role of the pharmacist on a general medicine acute care for the elderly unit.
AB  - BACKGROUND: The prevalence of prescription medication use increases with age, and
      older adults are at increased risk of harm from medication use. OBJECTIVE: To
      describe the role of a pharmacist on a General Medicine Acute Care of the Elderly
      (GM-ACE) Unit. METHODS: A job description was prepared, and a clinical pharmacist
      specializing in internal medicine was re-assigned to participate in
      multidisciplinary rounds on the ACE unit twice weekly and to work with a unit
      based pharmacist assigned to multiple units. The clinical pharmacist also
      provided formal education on geriatric pharmacotherapy for other health care
      providers. Interventions were defined as changes in the medical record and
      provision of drug information. Interventions were tracked with an existing form
      and sorted by category. Data on interventions were presented to the pharmacy and
      therapeutics committee routinely. RESULTS: After 3 months, the clinical
      pharmacist accomplished 76 interventions in the areas of agent selection, dose
      optimization, addition of therapy, deletion of therapy, medication
      reconciliation, intravenous to oral conversion, technology improvements, and drug
      information/patient education. CONCLUSION: Expanding the role of the pharmacist
      in a GM-ACE unit has improved the medication use process in a high-risk
      population through improvements in medication overuse, medication underuse,
      dosing, medication reconciliation, patient education, and health care provider
      education.

PMID- 22387109
TI  - Aging affects L-arginine and its metabolites in memory-associated brain
      structures at the tissue and synaptoneurosome levels.
AB  - L-arginine, one of the most metabolically versatile amino acids, can be
      metabolized to form a number of bioactive molecules. The present study
      systematically investigated age-related changes in L-arginine and its metabolites
      in the hippocampus, parahippocampal region, and prefrontal cortex at the tissue
      (crude homogenates) and synaptoneurosome (a subcellular preparation enriched for
      synaptic material) levels. As aging leads to reduced water content in the brain,
      age-related changes in neurochemical levels in tissue homogenates normalized by
      wet tissue weight and protein level were compared. There were significant
      differences in L-arginine, L-citrulline, L-ornithine, agmatine, putrescine,
      spermidine, spermine, and glutamate, but not GABA, in the CA1, CA2/3, and dentate
      gyrus sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal,
      and postrhinal cortices in 24 (aged) and 4 (young) months old rats in a region
      specific manner. The overall pattern of age-related changes in amino acids (L
      arginine, L-citrulline, L-ornithine, glutamate, and GABA) was largely similar
      between homogenates and synaptoneurosomes, whereas the pattern for the amines
      (agmatine, putrescine, spermidine, and spermine) was quite different.
      Furthermore, the pattern of age-related changes in neurochemical levels in tissue
      homogenates normalized by wet tissue weight and protein level was very similar
      for all 9 neurochemicals measured. These findings suggest that there are
      differential effects of aging on L-arginine metabolism at the tissue and
      synaptoneurosome levels and that the way of data normalization (tissue weight vs.
      protein level) has no or very minor effects on 9 neurochemicals measured.

PMID- 22387107
TI  - Sex, glia, and development: interactions in health and disease.
AB  - Microglia and astrocytes are the primary immune cells within the central nervous
      system. Microglia influence processes including neural development, synaptic
      plasticity and cognition; while their activation and production of immune
      molecules can induce stereotyped sickness behaviors or pathologies including
      cognitive dysfunction. Given their role in health and disease, we propose that
      glia may also be a critical link in understanding the etiology of many
      neuropsychiatric disorders that present with a strong sex-bias in their symptoms
      or prevalence. Specifically, males are more likely to be diagnosed with disorders
      that have distinct developmental origins such as autism or schizophrenia. In
      contrast, females are more likely to be diagnosed with disorders that present
      later in life, after the onset of adolescence, such as depression and anxiety
      disorders. In this review we will summarize the evidence suggesting that sex
      differences in the colonization and function of glia within the normal developing
      brain may contribute to distinct windows of vulnerability between males and
      females. We will also highlight the current gaps in our knowledge as well as the
      future directions and considerations of research aimed at understanding the link
      between neuroimmune function and sex differences in mental health disorders.

PMID- 22387108
TI  - c-Jun N-terminal kinase controls a negative loop in the regulation of glial
      fibrillary acidic protein expression by retinoic acid.
AB  - Glial fibrillary acidic protein (GFAP) is a protein widely used as a molecular
      marker for astroglial differentiation and mature astrocytes. We and others have
      shown previously that retinoic acid and specific cytokines induce the expression
      of GFAP in neural precursor cells by activating the phosphatidylinositol-4,5
      bisphosphate-3-kinase (PI3K) phosphorylation pathway. Here, we extend our
      previous work and show that retinoic acid also activates specifically the c-Jun N
      terminal kinase (JNK) phosphorylation pathway, which in turn inhibits GFAP
      expression. Our results suggest the existence of a negative self-regulatory loop
      in the phosphorylation pathways that regulates GFAP expression. This loop is
      constitutively repressed by the PI3K pathway. Our results could be relevant for
      disorders involving sustained GFAP overexpression in precursor cells, such as
      glioblastoma and Alexander disease.

PMID- 22387110
TI  - Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea
      pigs.
AB  - OBJECTIVE: To examine the efficiency of hydrogen-rich saline in the treatment of
      intensive noise-induced cochlear injury. MATERIALS AND METHODS: Forty guinea pigs
      were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich
      saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control),
      and NO TREATMENT (normal control) groups. The HS+NOISE, NS+NOISE, and NOISE ALONE
      groups were exposed to intensive noise (4 h at 115 dB SPL noise of 4000+/-100
      Hz). The auditory brainstem response (ABR) was used to examine the hearing
      threshold in each group. Distortion product otoacoustic emission (DPOAE) was used
      to examine outer hair cell function. We also examined cochlear morphology to
      evaluate inner and outer hair cell trauma induced by noise exposure. Hydrogen
      rich saline was administered twice daily for 6 days (2.5 ml/kg, i.p.) 24 h after
      noise exposure. RESULTS: Baseline ABR thresholds and DPOAE values were normal in
      all groups at the measured frequencies (2, 4, 8, and 16 kHz) before noise
      exposure. The ABR threshold shift was 50-55 dB across the frequencies tested, and
      average DPOAE declined in the NOISE ALONE, NS+NOISE, and HS+NOISE groups 24 h
      after noise exposure. However, the changes in cochlear parameters were different
      between groups. The HS+NOISE group showed a significantly decreased ABR threshold
      value as compared with the NS+NOISE or NOISE ALONE group (P<0.01) on day 7. The
      mean DPOAE recovered to some extent in the three noise exposure groups, but at
      most frequencies the HS+NOISE group showed significantly increased DPOAE on day 7
      as compared with the NS+NOISE group or NOISE ALONE group (P<0.01). Surface Corti
      organ preparations stained with succinate dehydrogenase (SDH) showed that most
      outer hair cells (OHCs) were still dropsical and a few were missing 7 days after
      noise exposure in the NS+NOISE group. Only a few OHCs were slightly dropsical in
      the HS+NOISE group. The numbers of missing hair cells 7 days after noise exposure
      were significantly greater in the NOISE ONLY and NS+NOISE groups than the
      HS+NOISE group (P<0.01). CONCLUSIONS: Hydrogen-rich saline can alleviate
      experimental noise-induced hearing loss in guinea pigs, partially by preventing
      the death of cochlear hair cells after intensive noise exposure.

PMID- 22387111
TI  - Postnatal dendritic development in lumbar motoneurons in mutant superoxide
      dismutase 1 mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by motoneuron (MN) degeneration and muscle paralysis. Cu/Zn
      superoxide dismutase (SOD1) mutant mice develop an ALS-like phenotype similar to
      that seen in human. Recently it has been shown in SOD1 mice that the excitability
      and morphology of spinal MNs are altered at postnatal age, long before overt
      clinical symptoms. In the present study, we examined the morphology of lumbar MNs
      in wild-type (WT) and SOD1(G85R) mice at two postnatal ages (P3-P4 and P8-P9)
      when differences in size and excitability were reported. Detailed morphological
      analysis was performed in MNs intracellularly labeled with Neurobiotin and 3D
      reconstructed using the NeurolucidaTM system. We showed that SOD1 MNs exhibited
      longer terminal segments than in the WT MNs at age P3-P4. This excessive
      elongation was followed by pathological ramification of all individual dendrites
      between P4 and P8. Abnormal bifurcations occurred at the terminal tips, and
      distance between consecutive bifurcations remained stable. Most dendrites of SOD1
      MNs performed in average two successive iterations of bifurcation during this
      short time. Our results suggest that the SOD1 MNs switch from excessive
      elongation to overbranching in a few days at early postnatal life, which might be
      a compensatory reaction to the possible variation of synaptic input.

PMID- 22387113
TI  - A cardiovascular role for fractalkine and its cognate receptor, CX3CR1, in the
      rat nucleus of the solitary tract.
AB  - The nucleus of the solitary tract (NTS), an integral vasomotor region located in
      the hindbrain, is important for cardiovascular homeostasis. Fractalkine (FKN) and
      its cognate receptor, CX3CR1, are constitutively expressed in the normal rat
      brain. The physiological significance of this cytokine and its receptor are not
      well established. In this study, we sought to identify the expression of FKN and
      CX3CR1 in subnuclei of the NTS and to elucidate their functional relevance. Using
      immunohistochemistry, we found expression of FKN and CX3CR1 throughout the entire
      rostro-caudal axis of the NTS in normal adult male Sprague-Dawley rats. When FKN
      was unilaterally microinjected directly into the commissural and sub-postremal,
      but not rostral, NTS, blood pressure and heart rate were significantly decreased
      when compared with saline controls. The FKN-induced depressor and bradycardic
      responses were inhibited by pretreatment with a phosphoinositide 3-kinase
      inhibitor, LY294002. These data suggest that the cytokine, FKN, and its receptor,
      CX3CR1, may modulate cardiovascular responses in the NTS of normal healthy rats
      via the phosphoinositide 3-kinase intracellular signaling pathway.

PMID- 22387112
TI  - Morphology and innervation of the vestibular lagena in pigeons.
AB  - The morphological characteristics of the pigeon lagena were examined using
      histology, scanning electron microscopy, and biotinylated dextran amine (BDA)
      neural tracers. The lagena epithelium was observed to lie partially in a
      parasagittal plane, but was also U-shaped with orthogonal (lateral) directed
      tips. Hair cell planar polarities were oriented away from a central reversal line
      that ran nearly the length of the epithelium. Similar to the vertebrate utricle
      and saccule, three afferent classes were observed based upon their terminal
      innervation pattern, which include calyx, dimorph, and bouton fibers. Calyx and
      dimorph afferents innervated the striola region of the lagena, whereas bouton
      afferents innervated the extrastriola and a small region of the central striola
      known as the type II band. Calyx units had large calyceal terminal structures
      that innervated only type I hair cells. Dimorph afferents innervated both type I
      and II hair cells, with calyx and bouton terminals. Bouton afferents had the
      largest most complex innervation patterns and the greatest terminal areas
      contacting many hair cells.

PMID- 22387114
TI  - Proteomics: The clinical link.

PMID- 22387115
TI  - Identification of olive (Olea europaea) seed and pulp proteins by nLC-MS/MS via
      combinatorial peptide ligand libraries.
AB  - Different types of extraction protocols are described for identifying proteins in
      seed and pulp of olive (Olea europea), by employing both conventional extraction
      methods and capture with ProteoMiner as well as with in house-made combinatorial
      peptide ligand libraries (HM-CPLLs) at pH 7.4 and at pH 2.2. Thanks to the use of
      CPLLs, able to dramatically amplify the signal of low-abundance species, a quite
      large number of compounds has been indeed identified: 61 in the seed (vs. only
      four reported in current literature) and 231 in the pulp (vs. 56 described so
      far), the deepest investigation up to the present of the olive proteome. In the
      seed, it highlights the presence of seed storage proteins, oleosins and histones.
      In the pulp, the allergenic thaumatin-like protein (Ole e 13) was confirmed,
      among the other 231, as the most abundant protein in the olive pulp. The present
      research has also been undertaken with the aim of identifying proteins in olive
      oil and ascertaining the relative contribution of seed and pulp proteins in their
      presence, if any, in oils.

PMID- 22387116
TI  - Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart
      tissue reveals immediate mitochondrial impairment after ionising radiation.
AB  - Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue
      is advancing the field of clinical proteomics. However, quantitative proteome
      analysis of FFPE tissue is hampered by the lack of an efficient labelling method.
      The usage of conventional protein labelling on FFPE tissue has turned out to be
      inefficient. Classical labelling targets lysine residues that are blocked by the
      formalin treatment. The aim of this study was to establish a quantitative
      proteomics analysis of FFPE tissue by combining the label-free approach with
      optimised protein extraction and separation conditions. As a model system we used
      FFPE heart tissue of control and exposed C57BL/6 mice after total body
      irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated
      proteins (p<=0.05) in irradiated hearts 24h after the exposure. The proteomics
      data were further evaluated and validated by bioinformatics and immunoblotting
      investigation. In good agreement with our previous results using fresh-frozen
      tissue, the analysis indicated radiation-induced alterations in three main
      biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism.
      The label-free approach enables the quantitative measurement of radiation-induced
      alterations in FFPE tissue and facilitates retrospective biomarker identification
      using clinical archives.

PMID- 22387117
TI  - Early-life gut microbiota under physiological and pathological conditions: the
      central role of combined meta-omics-based approaches.
AB  - The establishment of gut microbiota immediately after birth is modulated by
      different mechanisms that can be considered specific determinants of temporal and
      spatial variability. Over the last few years, molecular methods have been
      offering a complementary support to the classical microbiology, often
      underpowered by its inability to provide unbiased representation of gut
      microbiota. The advent of high-throughput-omics-based methods has opened new
      avenues in the knowledge of the gut ecosystem by shedding light on its shape and
      modulation. Such methods may unveil taxa distribution, role and density of
      microbial habitants, hence highlighting individual phenotyping (physiological
      traits) and their relationship with gut dysbiosis, inflammation processes,
      metabolic disorders (pathological conditions). Synergic meta-omics or "systems
      biology"-based approaches may concur in providing advanced information on
      microbiota establishment and pathogen control. During early-life stages this
      massive amount of data may provide gut microbiota descriptive and functional
      charts which can be exploited to perform a good practice in childcare and
      pediatrics, thus providing nutraceutical benefits and endorsing healthy
      development and aging. This article is part of a Special Issue entitled:
      Translational Proteomics.

PMID- 22387118
TI  - Network analysis and proteomic identification of vimentin as a key regulator
      associated with invasion and metastasis in human hepatocellular carcinoma cells.
AB  - Poor prognoses have long been associated with the high relapse and metastasis of
      human hepatocellular carcinoma (HCC). To achieve long-term survival, it is
      necessary to identify new HCC biomarkers and investigate their roles in cell
      mobility and invasiveness. Of note, overexpression of vimentin (Vim) was
      significantly correlated with tumor nuclear grade (p=0.01) and the invasive
      potential, indicating that Vim may be a promising candidate in regulating HCC
      metastasis. RNA interference-mediated silencing of Vim (siVim) suppressed the
      invasive and migratory propensity, and matrix metalloproteinase (MMP)-9 activity,
      and elicited morphological changes in poorly differentiated SK-Hep-1 cells.
      Moreover, we performed a comprehensive proteomic analysis to survey global
      protein changes mediated by siVim in SK-Hep-1 cells. Significant changes in
      cytoskeleton protein but not messenger RNA levels encoding these targeted
      proteins were observed. All of the data in the current study and a network
      analysis implied that abolition of Vim may disturb the expression and stability
      of various cytoskeletal proteins through promoting the ubiquitin system,
      resulting in impaired cell adhesion and motility. Collectively, an integrated
      approach represents a modality to explore novel relationships in a proteome
      complex and highlights the functional roles of Vim in HCC metastasis. This
      article is part of a Special Issue entitled: Translational Proteomics.

PMID- 22387119
TI  - The accuracy of measuring glenohumeral motion with a surface humeral cuff.
AB  - Conclusions about normal and pathologic shoulder motion are frequently made from
      studies using skin surface markers, yet accuracy of such sensors representing
      humeral motion is not well known. Nineteen subjects were investigated with flock
      of birds electromagnetic sensors attached to transcortical pins placed into the
      scapula and humerus, and a thermoplastic cuff secured on the arm. Subjects
      completed two repetitions of raising and lowering the arm in the sagittal,
      scapular and coronal planes, as well as shoulder internal and external rotation
      with the elbow at the side and abducted to 90 degrees . Humeral motion was
      recorded simultaneously from surface and bone fixed sensors. The average
      magnitude of error was calculated for the surface and bone fixed measurements
      throughout the range of motion. ANOVA tested for differences across angles of
      elevation, raising and lowering, and differences in body mass index. For all five
      motions tested, the plane of elevation rotation average absolute error ranged
      from 0-2 degrees , while the humeral elevation rotation average error ranged from
      0-4 degrees . The axial rotation average absolute error was much greater, ranging
      from 5 degrees  during elevation motions to approaching 30 degrees  at maximum
      excursion of internal/external rotation motions. Average absolute error was
      greater in subjects with body mass index greater than 25. Surface sensors are an
      accurate way of measuring humeral elevation rotations and plane of elevation
      rotations. Conversely, there is a large amount of average error for axial
      rotations when using a humeral cuff to measure glenohumeral internal/external
      rotation as the primary motion.

PMID- 22387120
TI  - A holistic approach to study the temporal variability in gait.
AB  - Movement variability has become an important field of research and has been
      studied to gain a better understanding of the neuro-muscular control of human
      movements. In addition to studies investigating "amplitude variability" there are
      a growing number of studies assessing the "temporal variability" in movements by
      applying non-linear analysis techniques. One limitation of the studies available
      to date is that they quantify variability features in specific, pre-selected
      biomechanical or physiological variables. In many cases it remains unclear if and
      to what degree these pre-selected variables quantify characteristics of the whole
      body movement. This technical note proposes to combine two analysis techniques
      that have already been applied for gait analysis in order to quantify variability
      features in walking with variables whose significance for the whole movements are
      known. Gait patterns were recorded using a full-body marker set on the subjects
      whose movements were captured with a standard motion tracing system. For each
      time frame the coordinates of all markers were interpreted as a high-dimensional
      "posture vector". A principal component analysis (PCA) conducted on these posture
      vectors identified the main one-dimensional movement components of walking.
      Temporal variability of gait was then quantified by calculating the maximum
      Lyapunov Exponent (LyE) of these main movement components. The effectiveness of
      this approach was demonstrated by determining differences in temporal variability
      between walking in unstable shoes and walking in a normal athletic-type control
      shoe. Several additional conceptual and practical advantages of this combination
      of analysis methods were discussed.

PMID- 22387121
TI  - Evaluation of a robot-assisted testing system for multisegmental spine specimens.
AB  - Mono- and multi-segmental testing methods are required to identify segmental
      motion patterns and evaluate the biomechanical behaviour of the spine. This study
      aimed to evaluate a new testing system for multisegmental specimens using a robot
      combined with an optical motion analysis system. After validation of the robotic
      system for accuracy, two groups of calf specimens (six monosegmental vs. six
      multisegmental) were mounted and the functional unit L3-4 was observed. Using
      rigid body markers, range of motion (ROM), elastic zone (EZ) and neutral zone
      (NZ), as well as stiffness properties of each functional spine unit (FSU) was
      acquired by an optical motion capture system. Finite helical axes (FHA) were
      calculated to analyse segmental movements. Both groups were tested in flexion and
      extension. A pure torque of 7.5 Nm was applied. Statistical analyses were
      performed using the Mann-Whitney U-test. Repeatability of robot positioning was 
      0.001+/-0.018 mm and -0.025+/-0.023 degrees  for translations and rotations,
      respectively. The accuracy of the optical system for the proposed set-up was
      0.001+/-0.034 mm for translations and 0.075+/-0.12 degrees  for rotations. No
      significant differences in mean values and standard deviations of ROM for L3-4
      compared to literature data were found. A robot-based facility for testing
      multisegmental spine units combined with a motion analysis system was proposed
      and the reliability and reproducibility of all system components were evaluated
      and validated. The proposed set-up delivered ROM results for mono- and multi
      segmental testing that agreed with those reported in the literature. Representing
      the FHA via piercing points determined from ROM was the first attempt showing a
      relationship between ROM and FHA, which could facilitate the interpretation of
      spine motion patterns in the future.

PMID- 22387122
TI  - In vitro hemodynamics and valve imaging in passive beating hearts.
AB  - Due to their high complexity, surgical approaches to valve repair may benefit
      from the use of in vitro simulators both for training and for the investigation
      of those measures which can lead to better clinical results. In vitro tests are
      intrinsically more effective when all the anatomical substructures of the
      valvular complexes are preserved. In this work, a mock apparatus able to house an
      entire explanted porcine heart and subject it to pulsatile fluid-dynamic
      conditions was developed, in order to enable the hemodynamic analysis of
      simulated surgical procedures and the imaging of the valvular structures. The
      mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter
      model. The left ventricle of an entire swine heart was dynamically pressurized by
      an external computer-controlled pulse duplicator. The ascending aorta was
      connected to a hydraulic circuit which simulated the input impedance of the
      systemic circulation; a reservoir passively filled the left atrium. Accesses for
      endoscopic imaging were located in the apex of the left ventricle and in the
      aortic root. The experimental pressure and flow tracings were comparable with the
      typical in vivo curves; a mean flow of 3.5+/-0.1l pm and a mean arterial pressure
      of 101+/-2 mmHg was obtained. High-quality echographic and endoscopic video
      recordings demonstrated the system's excellent potential in the observation of
      the cardiac structures dynamics. The proposed mock loop represents a suitable in
      vitro system for the testing of minimally-invasive cardiovascular devices and
      surgical procedures for heart valve repair.

PMID- 22387123
TI  - Optimizing whole-body kinematics to minimize valgus knee loading during
      sidestepping: implications for ACL injury risk.
AB  - The kinematic mechanisms associated with elevated externally applied valgus knee
      moments during non-contact sidestepping and subsequent anterior cruciate ligament
      (ACL) injury risk are not well understood. To address this issue, the residual
      reduction algorithm (RRA) in OpenSim was used to create nine subject-specific,
      full-body (37 degrees of freedom) torque-driven simulations of athletic males
      performing unplanned sidestep (UnSS) sport tasks. The RRA was used again to
      produce an optimized kinematic solution with reduced peak valgus knee torques
      during the weight acceptance phase of stance. Pre-to-post kinematic optimization,
      mean peak valgus knee moments were significantly reduced by 44.2 Nm (p=0.045).
      Nine of a possible 37 upper and lower body kinematic changes in all three planes
      of motion were consistently used during the RRA to decrease peak valgus knee
      moments. The generalized kinematic strategy used by all nine simulations to
      reduce peak valgus knee moments and subsequent ACL injury risk during UnSS was to
      redirect the whole-body center of mass medially, towards the desired direction of
      travel.

PMID- 22387124
TI  - Associations among childhood sexual abuse, language use, and adult sexual
      functioning and satisfaction.
AB  - OBJECTIVES: To better understand the link between childhood sexual abuse (CSA)
      and adult sexual functioning and satisfaction, we examined cognitive differences
      between women with (N=128) and without (NSA, N=99) CSA histories. METHODS: We
      used the Linguistic Inquiry Word Count, a computerized text analysis program, to
      investigate language differences between women with and without CSA histories
      when writing about their daily life (neutral essay) and their beliefs about
      sexuality and their sexual experiences (sexual essay). RESULTS: Compared to NSA
      women, women with CSA histories used fewer first person pronouns in the neutral
      essay but more in the sexual essay, suggesting women with CSA histories have
      greater self-focus when thinking about sexuality. Women who reported CSA used
      more intimacy words and more language consistent with psychological distancing in
      the sexual essay than did NSA women. Use of positive emotion words in the sexual
      essay predicted sexual functioning and satisfaction in both groups. CONCLUSIONS:
      These findings support the view that language use differs in significant ways
      between women with and without sexual abuse histories, and that these differences
      relate to sexual functioning and satisfaction.

PMID- 22387125
TI  - Prognostic features, human papillomavirus status, and epidermal growth factor
      receptor expression in oral squamous cell carcinoma in young adults.
AB  - PURPOSE: There is still debate in literature about the survival outcomes of
      patients who have cancer of the oral cavity when young. Hence the aims were (1)
      to estimate disease-free survival, overall survival, and cause-specific survival
      in patients who developed oral cavity squamous cell carcinoma between 18 and 40
      years of age and (2) to assess the clinicopathologic factors including detection
      of human papillomavirus and epidermal growth factor receptor (EGFR)
      overexpression in primary lesions affecting recurrence. METHODS: This is a
      retrospective case-note review and reevaluation of histopathologic slides of
      patients treated more than 25 years. Descriptive statistics, Cox proportional
      hazard models, and Kaplan-Meier survival curves were used for statistical
      analysis. RESULTS: A total of 62 patients were treated, with mean follow-up of
      11.4 years. Forty-five were oral tongue tumors and 43 had stage I or II disease.
      The 5-year disease-free survival was 73.5%. The 10-year overall survival and
      cause-specific survival rates were 81.8% and 83.4%, respectively. Smoking and
      alcohol intake were not seen as risk factors in this population. Multivariate
      modeling identified only nodal involvement as significantly associated with
      overall survival and only extracapsular spread as significantly associated with
      locoregional recurrence. At 5 years after treatment, the cause-specific survival
      was 100% for patients with low EGFR expression and 81.1% for patients with high
      EGFR expression (hazard ratio for high vs low, 3.1; 95% confidence interval, 0.4
      406.9; P = .46). Human papillomavirus was not detected in all but 2 tumor
      specimens. CONCLUSIONS: Survival outcomes are quite good in young patients with
      oral cancer.

PMID- 22387126
TI  - Characterisation of partial volume effect and region-based correction in small
      animal positron emission tomography (PET) of the rat brain.
AB  - Accurate quantification of PET imaging data is required for a useful
      interpretation of the measured radioactive tracer concentrations. The partial
      volume effect (PVE) describes signal dilution and mixing due to spatial
      resolution and sampling limitations, which introduces bias in quantitative
      results. In the present study we investigated the magnitude of PVE for volumes of
      interest (VOIs) in the rat brain and the effect of positron range. In simulated
      (11)C-raclopride studies we examined the influence of PVE on time activity curves
      in striatal and cerebellar VOIs and binding potential estimation. The performance
      of partial volume correction (PVC) was studied using the region-based geometric
      transfer matrix (GTM) method including the question of whether a spatially
      variant point spread function (PSF) is necessary for PVC of a rat brain close to
      the centre of the field of view. Furthermore, we determined the effect of
      spillover from activity outside the brain. The results confirmed that PVE is
      significant in rat brain PET and showed that positron range is an important
      factor that needs to be included in the PSF. There was considerable bias in time
      activity curves for the simulated (11)C-raclopride studies and significant
      underestimation of binding potential even for very small centred VOIs. Good
      activity recovery was achieved with the GTM PVC using a spatially invariant
      simulated PSF when no activity was present outside the brain. PVC using a simple
      Gaussian fit point spread function was not sufficiently accurate. Spillover from
      regions outside the brain had a significant impact on measured activity
      concentrations and reduced the accuracy of PVC with the GTM method using rat
      brain regions alone, except for the smallest VOI size but at the cost of
      increased noise. Voxel-based partial volume correction methods which inherently
      compensate for spillover from outside the brain might be a more suitable choice.

PMID- 22387127
TI  - On chronic rhinosinusitis and the prevalence of fungal sinus disease: problems of
      diagnostic accuracy and a proposed classification of chronic rhinosinusitis.
AB  - There is considerable controversy in the diagnosis and classification of the type
      of inflammation that is attributed to various forms of chronic rhinosinusitis
      (CRS). Specimens obtained during surgical treatment of CRS have been invaluable
      resources for identifying the underlying inflammatory process. The classification
      of sinus inflammation is based on histopathologic examination of these surgical
      specimens. Accurate identification of the pathology and standardized reporting
      are invaluable for postsurgical treatment options and our understanding of CRS.
      In a large multispecialty referral hospital where multiple surgeons and
      pathologists are involved in clinical practice, the lack of standardization in
      specimen collection, specimen processing, and reporting introduce several
      variables that make it extremely difficult for retrospective analysis. This
      report focuses on consecutive endoscopic sinus surgical procedures performed by 4
      different sinus surgeons over a period of 4 years in a Central Texas
      multispecialty hospital. This is an analysis of the reality of clinical practice
      without intervention. At the core of this analysis are pathology reporting
      practices for fungal sinus disease and the undesirable variables introduced by
      nonstandardized reporting. A practical classification of CRS based on pathology
      is proposed.

PMID- 22387128
TI  - Amino acids: chemistry, functionality and selected non-enzymatic post
      translational modifications.
AB  - The ultimate goal of proteomics is determination of the exact chemical
      composition of protein species, including their complete amino acid sequence and
      the identification of each modified side chain, in every protein in a biological
      sample and their quantification. We are still far from achieving this goal due to
      limitations in analytical methodology and data analysis but also due to the fact
      that we surely have not discovered all amino acid modifications that occur in
      nature. To detect modified side chains and to discover new, still unknown amino
      acid derivatives, an understanding of the chemistry of the reactive groups of
      amino acids is mandatory. This tutorial focuses on the chemistry of the amino
      acid side chains and addresses non-enzymatic modifications. By highlighting some
      exemplary reactions a glimpse of the huge diversity of modified amino acids
      provides the reader with sufficient insight into amino acid chemistry to raise
      the awareness for unexpected side chain modifications. We further introduce the
      reader to a terminology, which enables the comprehensive description of the exact
      chemical composition of a protein species, including its full amino acid sequence
      and all modifications of its amino acid side chains. This Tutorial is part of the
      International Proteomics Tutorial Programme (IPTP number 10).

PMID- 22387129
TI  - Mitochondrial proteome analysis reveals depression of the Ndufs3 subunit and
      activity of complex I in diabetic rat brain.
AB  - Type-1 diabetes resulting from defective insulin secretion and consequent
      hyperglycemia, is associated with "diabetic encephalopathy." This is
      characterized by brain neurophysiological and structural changes resulting in
      impairment of cognitive function. The present proteomic analysis of brain
      mitochondrial proteins from streptozotocin-induced type-1 diabetic rats, shows a
      large decrement of the Ndufs3 protein subunit of complex I, decreased level of
      the mRNA and impaired catalytic activity of the complex in the diabetic rats as
      compared to controls. The severe depression of the expression and enzymatic
      activity of complex I can represent a critical contributing factor to the onset
      of the diabetic encephalopathy in type-1 diabetes.

PMID- 22387130
TI  - An MRM-based workflow for quantifying cardiac mitochondrial protein
      phosphorylation in murine and human tissue.
AB  - The regulation of mitochondrial function is essential for cardiomyocyte
      adaptation to cellular stress. While it has long been understood that
      phosphorylation regulates flux through metabolic pathways, novel phosphorylation
      sites are continually being discovered in all functionally distinct areas of the
      mitochondrial proteome. Extracting biologically meaningful information from these
      phosphorylation sites requires an adaptable, sensitive, specific and robust
      method for their quantification. Here we report a multiple reaction monitoring
      based mass spectrometric workflow for quantifying site-specific phosphorylation
      of mitochondrial proteins. Specifically, chromatographic and mass spectrometric
      conditions for 68 transitions derived from 23 murine and human phosphopeptides,
      and their corresponding unmodified peptides, were optimized. These methods
      enabled the quantification of endogenous phosphopeptides from the outer
      mitochondrial membrane protein VDAC, and the inner membrane proteins ANT and ETC
      complexes I, III and V. The development of this quantitative workflow is a
      pivotal step for advancing our knowledge and understanding of the regulatory
      effects of mitochondrial protein phosphorylation in cardiac physiology and
      pathophysiology. This article is part of a Special Issue entitled: Translational
      Proteomics.

PMID- 22387131
TI  - Keratins in oral cancer: necessity of mass spectrometry for validation of
      antibody based identifications.
AB  - Keratins are intermediate filament family proteins which are predominantly
      expressed in the epithelial cells. Most of the studies which evaluate the status
      of keratins in clinical samples of the oral cavity are based on the
      identification of their presence and localization by immunohistochemistry using
      monoclonal antibodies. It is very well known that many monoclonal/polyclonal
      antibodies show cross-reactivity with the other closely related or non-related
      proteins. This cross-reactivity might be the result of epitope similarity, but it
      is not always necessary. Therefore studies done with only antibody based
      techniques can mislead interpretation unless they are validated with additional
      techniques like mass-spectrometry. In this investigation we have evaluated the
      status of keratin 18 in cancer of buccal mucosa using 1DE, 2DE and western
      blotting with monoclonal antibody to keratin 18. The patterns emerging showed
      aberrant as well as differential expression of K18 in adjacent normal versus
      tumor tissue samples of buccal mucosa. Mass spectrometry analysis of the
      immunodetected spots however revealed that it is keratin 13. Thus this study
      emphasizes the necessity of validation of antibody based findings when dealing
      with proteins of a large family having similarity/homology in amino acid
      sequence.

PMID- 22387132
TI  - Crystal structure of sarcoplasmic reticulum Ca2+-ATPase (SERCA) from bovine
      muscle.
AB  - The SERCA pump, a membrane protein of about 110kDa, transports two Ca(2+) ions
      per ATP hydrolyzed from the cytoplasm to the lumen of the sarcoplasmic reticulum.
      In muscle cells, its ability to remove Ca(2+) from the cytosol induces
      relaxation. The transport mechanism employed by the enzyme from rabbit muscle has
      been extensively studied, and several crystal structures representing different
      conformational states are available. However, no structure of the pump from other
      sources is known. In this paper we describe the crystal structure of the bovine
      enzyme, crystallized in the E1 conformation and determined at 2.9A resolution.
      The overall molecular model is very similar to that of the rabbit enzyme, as
      expected by the high amino acid sequence identity. Nevertheless, the bovine
      enzyme has reduced catalytic activity with respect to the rabbit enzyme. Subtle
      structural modifications, in particular in the region of the long loop that
      protrudes into the SR lumen connecting transmembrane alpha-helices M7 and M8, may
      explain the difference.

PMID- 22387133
TI  - Cofactor biosynthesis through protein post-translational modification.
AB  - Post-translational modifications of amino acids can be used to generate novel
      cofactors capable of chemistries inaccessible to conventional amino acid side
      chains. The biosynthesis of these sites often requires one or more enzyme or
      protein accessory factors, the functions of which are quite diverse and often
      difficult to isolate in cases where multiple enzymes are involved. Herein is
      described the current knowledge of the biosynthesis of urease and nitrile
      hydratase metal centers, pyrroloquinoline quinone, hypusine, and tryptophan
      tryptophylquinone cofactors along with the most recent work elucidating the
      functions of individual accessory factors in these systems. These examples
      showcase the breadth and diversity of this continually expanding field.

PMID- 22387134
TI  - Recent developments in research on water oxidation by photosystem II.
AB  - Photosynthetic water oxidation chemistry at the unique manganese-calcium complex
      of photosystem II (PSII) is of fundamental importance and serves as a paragon in
      the development of efficient synthetic catalysts. A recent crystal structure of
      PSII shows the atoms of the water-oxidizing complex; its Mn4CaO5 core resembles
      inorganic manganese-calcium oxides. Merging of crystallographic and spectroscopic
      information reverses radiation-induced modifications at the Mn-complex in silico
      and facilitates discussion of the O-O bond chemistry. Coordinated proton
      movements are promoted by a water network connecting the Mn4CaO5 core with the
      oxidant, a tyrosine radical and one possibly mobile chloride ion. A basic
      reaction-cycle model predicts an alternating proton and electron removal from the
      catalytic site, which facilitates energetically efficient water oxidation.

PMID- 22387135
TI  - Iron-sulfur cluster sensor-regulators.
AB  - Regulatory proteins that contain an iron-sulfur cluster cofactor constitute a
      group that is growing both in number and importance, with a range of functions
      that include sensing of molecular oxygen, stress response, and iron regulation.
      In all cases, the cluster plays a central role, as a sensory module, in
      controlling the activity of the regulator. In some cases, the cluster is required
      for the protein to attain its regulatory form, while in others the active form
      requires loss or modification of the cluster. In this way, nature has exploited
      the inherent reactivity of iron-sulfur clusters. Here, we focus on recent
      advances that provide new insight into the remarkable chemistries exhibited by
      these regulators, and how they achieve the required levels of sensitivity and
      specificity.

PMID- 22387136
TI  - Anthocyanins from the seed coat of black soybean reduce retinal degeneration
      induced by N-methyl-N-nitrosourea.
AB  - Anthocyanins are known to have antioxidant effects and thus may play an important
      role in preventing various degenerative diseases. In this study, we examined the
      effect of anthocyanins extracted from the seed coat of black soybean on an animal
      model of retinal degeneration (RD), a leading cause of photoreceptor cell death
      resulting in blindness. RD was induced in rats by an intraperitoneal injection of
      N-methyl-N-nitrosourea (MNU) (50mg/kg), a DNA-methylating agent that causes
      photoreceptor damage. Anthocyanins extracted from black soybean seed coat
      (50mg/kg) were daily administered, orally, for 1, 2, and 4 weeks after MNU
      injection. Electroretinographic (ERG) recordings and morphological analyses were
      performed. In control rats with MNU-induced retinal damage, the ERG recordings
      showed a gradual significant time-dependent reduction in both a- and b-wave
      amplitudes compared with those of normal animals. In the MNU-induced RD rats
      given anthocyanins for 4 weeks, ERG responses were significantly increased
      compared with untreated RD rats, more apparently in scotopic stimulation than in
      the photopic condition. However, in the MNU-injected rats given anthocyanins for
      1 and 2 weeks, the increase in ERG responses was not significant.
      Morphologically, the outer nuclear layer, where photoreceptors reside, was well
      preserved in the anthocyanin-treated rat retinas throughout the experimental
      period. In addition, retinal injury, evaluated by immunolabeling with an antibody
      against glial fibrillary acidic protein, was markedly reduced in anthocyanin
      treated retinas. These results demonstrate that anthocyanins extracted from black
      soybean seeds can protect retinal neurons from MNU-induced structural and
      functional damages, suggesting that anthocyanins from black soybean seed coat may
      be used as a useful supplement to modulate RD.

PMID- 22387137
TI  - Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid
      explants following selective retina therapy (SRT): towards slowing the macular
      ageing process.
AB  - The purpose of this study was to investigate release of matrix metalloproteinases
      (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after
      Selective Retina Therapy (SRT) with laser energy levels below and above the
      threshold of RPE cell death. Following exposure to SRT using a prototype pulsed
      Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with
      Bruch's membrane and choroid were cultured in modified Ussing chambers which
      separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE
      monolayer. Threshold energy for RPE cell death and wound healing were determined
      with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were
      quantified within tissue samples and in the culture medium of the apical and
      basal compartments of the Ussing chamber using gelatine zymography. Laser
      energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140
      mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80
      and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a
      transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP
      2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments,
      respectively, without alterations in the apical compartment. Pro-MMP 2 levels
      were also significantly increased in all compartments (p < 0.05). Release of MMP
      9 was not altered. Laser energy below the threshold of RPE cell death did not
      alter the release of MMP 2 or 9. The findings suggest that the release of active
      MMP 2 on the basal side of the RPE during wound healing following SRT may address
      age-related pathological changes of Bruch's membrane with a potential to slow
      degenerative macular ageing processes before irreversible functional loss has
      occurred.

PMID- 22387138
TI  - Assessment of talipes equinovarus treated by Ponseti technique: three-year
      preliminary report.
AB  - BACKGROUND: The Ponseti method has become increasingly popular in the treatment
      of congenital talipes equinovarus (CTEV). Current methods of assessment focus on
      clinical, functional and radiological outcomes which are subjective and often
      difficult to repeat. However, integration of biomechanical evaluation can provide
      objective and quantifiable analysis. This study aims to evaluate the treatment
      outcome of CTEV patients on the basis of long-term clinical, functional and
      biomechanical assessment. METHODS: Following treatment, five children with CTEV
      were reviewed annually for the period 2008-2010. Clinical and functional outcomes
      were graded using parental questionnaires and clinical examination. Biomechanical
      parameters were evaluated using digital foot pressure studies. RESULTS: The study
      group recorded good clinical and functional outcomes. However, biomechanical
      studies have been able to identify subtle abnormalities that would be unapparent
      otherwise on clinical examination. CONCLUSIONS: It is recommended that
      biomechanical assessment be integrated into the overall evaluation of the outcome
      of CTEV after treatment.

PMID- 22387139
TI  - Donor B-type natriuretic peptide predicts early cardiac performance after heart
      transplantation.
AB  - BACKGROUND: Decision processes in heart donation remain difficult and are often
      based on subjective evaluation. We measured B-type natriuretic peptide (BNP) in
      heart donors and analyzed its value as a discriminator for early post-transplant
      cardiac performance. METHODS: Blood samples were prospectively obtained in 94
      brain-dead patients, among whom 56 were scheduled for heart donation. BNP values
      were not available prior to donor selection. BNP of heart donors was related to
      invasively measured cardiac output and hemodynamic parameters, early after
      transplantation. RESULTS: BNP, expressed as median (interquartile range), was 65
      (32 to 149) pg/ml in brain-dead donors scheduled for heart donation. BNP was
      higher (287 pg/ml, range 65 to 457; p = 0.0001) in donors considered ineligible
      for heart donation. In 45 heart recipients, cardiac output (CO) of 5.6 (4.8 to
      6.2) liters/min was measured at Day 12 (10-15). In the univariate analysis,
      recipient CO correlated significantly with donor BNP (r = -0.34, p = 0.025).
      Stepwise multiple regression, including donor variables such as body mass index,
      age, BNP, norepinephrine dose, gender and total ischemic time, identified donor
      BNP and age as the best independent predictors of CO in recipients (p = 0.02 and
      p = 0.005, respectively, R(2) of the model = 0.27). Donor BNP of >160 pg/ml had
      89% accuracy to predict poor cardiac performance in the recipient (cardiac index
      <2.2 liters/min/m(2)). High donor BNP was independently correlated with a longer
      hospital stay. CONCLUSIONS: Donor BNP was found to be related to cardiac
      performance, early after cardiac transplantation. BNP measurement in heart donors
      could become a useful tool in the evaluation of donor hearts.

PMID- 22387140
TI  - Relationship between oxidative stress and clinical-pathological aspects in dogs
      experimentally infected with Rangelia vitalii.
AB  - The aim of this study was to evaluate lipid peroxidation, protein oxidation and
      activity of enzymes that are indicators of oxidative stress in Rangelia vitalii
      infection in dogs. Animals were divided into two groups: negative control (n=5)
      and infected with R. vitalii (n=7). After inoculation, the parasitemia was
      estimated daily by microscopic examination of smears. Lipid peroxidation (TBARS)
      and advanced oxidation protein products (AOPP); and delta-aminolevulinate
      dehydratase (delta-ALA-D), superoxide dismutase (SOD) and catalase (CAT)
      activities in blood were evaluated. The samples were collected at days 10 and 20
      post-inoculation (PI). TBARS and AOPP levels were higher in the infected group in
      both analyzed periods (P<0.01). The delta-ALA-D activity was reduced in blood of
      dogs infected with R. vitalii on days 10 and 20 PI. SOD activity was
      significantly increased (P<0.01) in the blood of dogs infected with R. vitalii at
      days 10 and 20 PI, while CAT activity was significantly increased (P<0.01) only
      at day 20 PI when compared to non-infected animals. A positive correlation was
      observed between the degree of parasitemia and TBARS and AOPP levels and activity
      of antioxidant enzymes. The delta-ALA-D activity was negatively correlated with
      the degree of parasitemia. Based on the increased levels of TBARS, AOPP, SOD and
      CAT activities, and inhibition delta-ALA-D activity, we concluded that dogs
      experimentally infected with R. vitalii develop a state of redox unbalance and
      that these changes might be involved in the pathophysiology of disease.

PMID- 22387141
TI  - Genotypic variations in photosynthetic and physiological adjustment to potassium
      deficiency in cotton (Gossypium hirsutum).
AB  - A hydroponic culture experiment was conducted to determine genotypic variation in
      photosynthetic rate and the associated physiological changes in response to
      potassium (K) deficiency in cotton (Gossypium hirsutum L.) seedlings with
      contrasting two cotton cultivars in K efficiency. The K-efficient Liaomian18
      produced 66.7% more biomass than the K-inefficient NuCOTN99(B) under K
      deficiency, despite their similar biomass under K sufficiency. Compared with
      NuCOTN99(B), Liaomian18 showed 19.4% higher net photosynthetic rate (P(n), per
      unit leaf area) under K deficient solutions and this was associated with higher
      photochemical efficiency and faster export of soluble sugars from the phloem. The
      lower net P(n) of NuCOTN99(B) was attributed to higher capacity for nitrate
      assimilation and lower export of soluble sugars. Furthermore, NuCOTN99(B) showed
      38.4% greater ETR/P(n) than Liaomian18 under K deficiency, indicating that more
      electrons were driven to other sinks. Higher superoxide dismutase (SOD) and lower
      catalase (CAT) and ascorbate peroxidase (APX) activities resulted in higher
      levels of reactive oxygen species (ROS; e.g. O(2)(-)and H(2)O(2)) in NuCOTN99(B)
      relative to Liaomian18. Thus, the K inefficiency of NuCOTN99(B), indicated by
      lower biomass and net P(n) under K deficiency, was associated with excessively
      high nitrogen assimilation, lower export of carbon assimilates, and greater ROS
      accumulation in the leaf.

PMID- 22387142
TI  - Clinical predictors cannot replace biological predictors in HIV-2 infection in a
      community setting in West Africa.
AB  - OBJECTIVE: To identify clinical predictors of mortality in HIV-2-infected
      individuals that may be used in place of CD4 count or plasma viral load (PVL) to
      guide treatment management in resource-limited settings. METHODS: A prospective
      community cohort study of HIV-infected and HIV-negative individuals in a rural
      area of Guinea-Bissau has been ongoing since 1989. In 2003 participants were
      invited for a clinical examination and blood tests. They were followed-up for
      vital status until 2010. Antiretroviral treatment (ART) became available in 2007.
      Cox regression was used to examine the association of clinical measures (World
      Health Organization (WHO) stage, body mass index (BMI), mid-upper arm
      circumference (MUAC), and WHO performance scale) measured in 2003 with subsequent
      mortality. RESULTS: In 2003, 146 HIV-2-infected individuals (68% women; mean age
      56 years) were examined. Over the next 7 years, 44 (30%) died. BMI<18.5kg/m(2)
      was associated with a crude mortality hazard ratio (HR) of 1.9 (95% confidence
      interval (CI) 1.0-3.9, p=0.08); adjusted for age and sex, HR 1.8 (95% CI 0.9-3.8,
      p=0.1). MUAC <230mm in women and <240mm in men was also associated with an
      elevated mortality HR, though statistical evidence was weak (crude HR 2.2, 95% CI
      0.9-5.3, p=0.1). WHO clinical stage and WHO performance scale were not associated
      with mortality (p=0.6 and p=0.2, respectively, for crude associations).
      CONCLUSIONS: Baseline BMI, MUAC, WHO stage, and WHO performance scale were not
      strong or statistically significant predictors of mortality among HIV-2-infected
      individuals. CD4 count and PVL are more reliable tools, when available, for the
      management of HIV-2-infected patients in the community setting.

PMID- 22387143
TI  - Epidemiology, microbiology, and treatment considerations for bacterial pneumonia
      complicating influenza.
AB  - Post-influenza bacterial pneumonia is a major cause of morbidity and mortality
      associated with both seasonal and pandemic influenza virus illness. However,
      despite much interest in influenza and its complications in recent years, good
      clinical trial data to inform clinicians in their assessment of treatment options
      are scant. This paucity of evidence needs to be addressed urgently in order to
      improve guidance on the management of post-influenza bacterial pneumonia. The
      objectives of the current article are to evaluate the emergence of the 2009 H1N1
      influenza pandemic and use this information as background for an in-depth review
      of the epidemiology of bacterial pneumonia complicating influenza, to review the
      bacterial pathogens most likely to be associated with post-influenza bacterial
      pneumonia, and to discuss treatment considerations in these patients. When
      determining optimal management approaches, both antiviral and antibacterial
      agents should be considered, and their selection should be based upon a clear
      understanding of how their mechanisms of action intervene in the pathogenesis of
      post-influenza acute bacterial pneumonia.

PMID- 22387144
TI  - Immunogenicity of a Haemophilus influenzae type b-tetanus conjugate vaccine when
      administered separately or in combined vaccines for primary immunization in two
      consecutive national schedules in Turkey.
AB  - BACKGROUND: In Turkey, the Haemophilus influenzae type b-tetanus toxoid conjugate
      vaccine (Hib) was replaced by the combined diphtheria-tetanus-acellular pertussis
      and inactivated polio vaccine (DTaP-IPV/Hib) in 2008. This shift to the new
      schedule created different cohorts of vaccinated children as a consequence of the
      different schedules used. We evaluated the immunogenicity of the Hib vaccine in
      infants vaccinated with these different schedules. METHODS: Three groups of
      children were evaluated: group 1 comprised 145 infants vaccinated with
      diphtheria, tetanus, and whole cell pertussis (DTwP), oral polio vaccine (OPV),
      and Hib vaccines simultaneously at separate sites; group 2 comprised 204 infants
      vaccinated with the DTaP-IPV/Hib combined vaccine; group 3 comprised 100 infants
      vaccinated with a mixed schedule of DTwP, OPV, and Hib for the first one or two
      doses, followed by DTaP-IPV/Hib vaccine to complete the series. RESULTS: Anti
      polyribosylribitol phosphate (anti-PRP) titers >=0.15MUg/ml were similar in
      groups 1, 2, and 3. However, in group 1, who received all the vaccines at
      separate sites, >= l.0MUg/ml long-lasting antibody titers and anti-PRP geometric
      mean titers were higher (p=0.001). CONCLUSION: This study showed that even one
      dose administered in combination with other vaccines in a primary series
      decreased the level of anti-PRP.

PMID- 22387145
TI  - The impact of pharmacogenetics on radiation therapy outcome in cancer patients. A
      focus on DNA damage response genes.
AB  - More than half of cancer patients are treated by radiation therapy, with a wide
      inter-patient variability in tumour response. Recent advances have been made in
      understanding molecular mechanisms that govern the behaviour of tumour cells and
      tissues exposed to ionizing radiation. Accumulating data suggest an important
      role of DNA damage response genes, including DNA repair (especially double-strand
      breaks), apoptosis and cell-cycle control genes. It has been hypothesized that
      frequent germinal polymorphisms, most often single-nucleotide polymorphisms, in
      DNA damage response genes may impact tumour response and clinical outcome for
      patients receiving a radiotherapy-based treatment. We reviewed literature
      covering the relationships between candidate gene polymorphisms in DNA damage
      response and the efficacy of a radiation-based treatment. Although several
      methodological limitations may preclude a definitive conclusion, single
      nucleotide polymorphisms of several candidate genes such as ERCC- or XRCC-family
      genes seem to be potential predictive biomarkers of radiotherapy efficacy, even
      though not strictly involved in radiotherapy-induced double-strand breaks repair.
      In order to improve the relevance of clinical results, and our interpretation of
      them, we draw a parallel between clinical findings and available preclinical data
      on polymorphism functionality. Clinical findings require validation in larger
      replication studies and open the prospect of future clinical trials.

PMID- 22387146
TI  - Transesophageal and contact ultrasound echographic assessments of pulmonary
      vessels in bilateral lung transplantation.
AB  - BACKGROUND: Intraoperative transesophageal echocardiographic visualization of the
      vascular anastomosis of lung grafts can be difficult. The goal of this
      prospective study was to compare intraoperative transesophageal echocardiography
      and contact ultrasound. METHODS: Vessel imaging and Doppler analysis obtained
      before chest closure by both techniques were compared in 18 bilateral lung
      transplant recipients. RESULTS: Twenty-four arteries in 36 and 45 pulmonary veins
      in 72 were recorded using transesophageal echocardiography versus 34 and 60 by
      contact ultrasound (p = 0.05). Views of the left pulmonary artery (p = 0.04) and
      of the left superior and inferior pulmonary veins (p = 0.04 and p = 0.02,
      respectively) were more often obtained with contact ultrasound. Measurements of
      vessel diameters were similar by both methods except for the left superior vein,
      which was smaller by the transesophageal approach (p = 0.002). In 1 patient,
      inferior venous diameters could not be obtained by either method. Nine arterial
      and 47 venous velocities were recorded by transesophageal echocardiography versus
      21 and 33 by contact ultrasound (p = 0.001). Contact ultrasound produced better
      left pulmonary artery recordings (p = 0.02), whereas transesophageal
      echocardiography was more effective on venous velocities. Left inferior vein
      velocity was twofold higher using transesophageal echocardiography (p < 0.001).
      CONCLUSIONS: These results suggest clinicians should exercise caution when making
      treatment decisions when using transesophageal echocardiography alone.

PMID- 22387147
TI  - Raman microspectroscopy as a non-invasive tool to assess the vitrification
      induced changes of ovine oocyte zona pellucida.
AB  - Cryopreservation-induced modifications of zona pellucida (ZP) have been explored
      to a lesser extent compared to other oocyte compartments. Different methods have
      been applied to identify ZP changes, but most of them are invasive and measure
      only few properties of ZP. Raman microspectroscopy (RMS) is a powerful technique
      for studying the molecular composition of cells but to date few studies have been
      performed on the oocytes using this method. The aim of the present study is to
      investigate the structural modifications of ZP of vitrified/warmed in vitro
      matured ovine oocytes by means of RMS. Cumulus-oocyte complexes were recovered
      from the ovaries of slaughtered adult sheep, matured in vitro and vitrified
      following the Minimum Essential Volume method using cryotops. ZPs of
      vitrified/warmed oocytes (VITRI), were exposed to vitrification solutions but not
      cryopreserved (CPA-exp) and untreated oocytes (CTR) were analyzed by RMS. We
      focused our analysis on the ZP protein and carbohydrate components by analyzing
      the 1230-1300 cm(-1) amide III region and the 1020-1140 cm(-1) spectral range in
      RMS spectra, respectively. The spectral profiles in the ranges of proteins and
      carbohydrates were comparable between CTR and CPA-exp ZPs, whereas VITRI ZPs
      showed a significantly altered protein secondary structure characterized by an
      increase in beta-sheet content and a decrease in the alpha-helix content. A
      significant modification of the carbohydrate components was also observed. This
      study demonstrates that vitrification of ovine oocytes induces biochemical
      changes of ZP related to the secondary structure of proteins and carbohydrate
      residues. Cryoprotectants do not strongly alter the molecular composition of ZP
      which is affected mainly by cooling. Raman technology offers a powerful and non
      invasive tool to assess molecular modifications induced by cryopreservation in
      oocytes.

PMID- 22387148
TI  - PFAA Days III meeting report and highlights.

PMID- 22387150
TI  - An online randomised controlled trial to assess the feasibility, acceptability
      and potential effectiveness of 'Living with Bipolar': a web-based self-management
      intervention for bipolar disorder: trial design and protocol.
AB  - BACKGROUND: Bipolar Disorder (BD) is a common and severe form of mental illness.
      Pharmacotherapy is the main treatment offered, but has limited effectiveness, and
      there is increasing evidence that people with BD respond well to psychological
      interventions. Inequalities in access to face-to-face psychological interventions
      mean many people seek support outside of routine health services. AIM: To assess
      a recovery informed web-based self-management intervention for BD to increase
      access to psychological support. METHOD: A small online randomised controlled
      trial (RCT) will evaluate the feasibility, acceptability and potential
      effectiveness of the intervention compared to treatment as usual (TAU).
      Feasibility and acceptability will be assessed by recruitment, adherence and
      dropout rates, website usage statistics, user satisfaction scales and a series of
      qualitative interviews. Effectiveness will be assessed on a range of outcome
      measures including quality of life, mood symptoms, coping, recovery, and illness
      beliefs. ANALYSIS: Rates of adherence and dropout will be analysed using logistic
      regression models with health, socioeconomic and treatment factors as explanatory
      variables. Changes in quality of life mean scores, contrasting between arms, will
      be assessed using random effects models. An exploratory analysis will be
      performed on the secondary outcomes. Thematic analysis (Braun & Clarke, 2006)
      will be used to analyse the qualitative interviews. DISCUSSION: The benefits,
      challenges and methodological challenges of developing a web-based intervention
      and conducting an RCT online are discussed. CONCLUSION: The results of this trial
      will inform a definitive trial; and the implementation phase will aim to assess
      the potential for use within the NHS.

PMID- 22387149
TI  - CpG methylation recruits sequence specific transcription factors essential for
      tissue specific gene expression.
AB  - CG methylation is an epigenetically inherited chemical modification of DNA found
      in plants and animals. In mammals it is essential for accurate regulation of gene
      expression and normal development. Mammalian genomes are depleted for the CG
      dinucleotide, a result of the chemical deamination of methyl-cytosine in CG
      resulting in TpG. Most CG dinucleotides are methylated, but ~15% are
      unmethylated. Five percent of CGs cluster into ~20,000 regions termed CG islands
      (CGI) which are generally unmethylated. About half of CGIs are associated with
      housekeeping genes. In contrast, the gene body, repeats and transposable elements
      in which CGs are generally methylated. Unraveling the epigenetic machinery
      operating in normal cells is important for understanding the epigenetic
      aberrations that are involved in human diseases including cancer. With the advent
      of high-throughput sequencing technologies, it is possible to identify the CG
      methylation status of all 30million unique CGs in the human genome, and monitor
      differences in distinct cell types during differentiation and development. Here
      we summarize the present understanding of DNA methylation in normal cells and
      discuss recent observations that CG methylation can have an effect on tissue
      specific gene expression. We also discuss how aberrant CG methylation can lead to
      cancer. This article is part of a Special Issue entitled: Chromatin in time and
      space.

PMID- 22387151
TI  - Association of SLC11A1 (NRAMP1) polymorphisms with pulmonary Mycobacterium avium
      complex infection.
AB  - Although genetic variants in SLC11A1 (NRAMP1) have been associated with
      mycobacterial diseases, these findings have not been extensively validated in
      pulmonary Mycobacterium avium complex (MAC) infection. This study investigated
      the genomic structure of SLC11A1 and its association with MAC infection. Nineteen
      polymorphic loci were genotyped in European descendents and the Japanese
      population. Linkage disequilibrium (LD) structures and frequencies of major
      haplotypes differed between these 2 populations. Tag single nucleotide
      polymorphisms (SNPs) were chosen from the data set, and 6 polymorphic sites were
      genotyped in 122 pulmonary MAC cases and 211 controls from Japan. We observed
      that the T allele of rs2279014 in the 3' untranslated region was associated with
      protection from MAC disease when comparing allele frequencies with an odds ratio
      of 0.582 (95% confidence interval 0.379-0.894, p = 0.013). The frequencies of
      haplotypes constructed with the above 6 variants did not differ between cases and
      controls. Allele-specific expression imbalance of SLC11A1 mRNA was evaluated in
      peripheral blood cells from heterozygous individuals, but no difference was
      observed among haplotypes. Although the significance was modest, rs2279014 is in
      strong LD with nearby SNPs and further studies are required for conclusive
      validation.

PMID- 22387152
TI  - Specific antibodies reacting with simian virus 40 capsid protein mimotopes in
      serum samples from healthy blood donors.
AB  - Simian virus 40 (SV40), a small DNA tumor virus, was inadvertently administered
      to human populations with the use of contaminated vaccines. SV40 sequences have
      mainly been detected in healthy individuals and cancer patients using polymerase
      chain reaction techniques. However, some studies have failed to reveal the
      presence of SV40 in human specimens. These conflicting results indicate the need
      for new research to verify whether SV40 is circulating in humans. Mimotopes from
      SV40 structural peptides were tested to investigate for specific reactions to
      human sera antibodies. An indirect enzyme-linked immunosorbent assay with
      synthetic peptides from SV40 viral capsid proteins 1-2-3 (VPs 1-2-3) was set up
      and employed to test 855 serum samples from healthy blood donors. Data from
      immunologic assays indicate that serum antibodies against SV40 VP mimotopes are
      detectable, although with a low titer, in blood donors 18 to 65 years old. The
      overall prevalence of serum samples that reacted with the 2 SV40 VP peptides was
      18%. The strong points for this novel method include the simplicity of its
      approach and the potential to discriminate between SV40-specific antibody
      responses and to draw correlations between responses to the 2 independent SV40
      peptides. These data suggest that SV40, or a yet undetected closely related
      polyomavirus, is circulating in human populations, but with lower prevalence than
      that of the ubiquitous BK and JC human polyomaviruses.

PMID- 22387153
TI  - Changes in immunologic parameters of humoral immunity and adipocytokines in obese
      persons are gender dependent.
AB  - The aim of this study was to investigate several immunologic parameters using of
      immunonephelometry and adipocytokines by the enzyme immunoassay and their changes
      in different states of obesity. Obesity is considered to involve a state of
      chronic low-grade inflammation, with links between adipose cells and the immune
      system. We found significantly higher complement C3 levels in all obese subjects.
      Levels of the complement C4 were significantly higher in obese women, but not in
      men, when compared with the corresponding group of normal weight subjects. The
      increase in C-reactive protein concentrations was significant in both obese and
      morbidly obese women, but only in morbidly obese men. No significant differences
      in tumor necrosis factor-alpha, interleukin-6, interleukin-10, and soluble
      intercellular adhesion molecule-1 were found. sE-selectin levels were higher in
      both overweight and obese women but only in morbidly obese men. We found
      decreased adiponectin concentrations in obese and morbidly obese women.
      Concentrations of leptin were significantly higher only in obese men (p < 0.05),
      whereas in women the increase in leptin levels was significant in overweight,
      obese, and morbidly obese subjects. In conclusion, our results demonstrate
      elevated levels of C3, C-reactive protein, sE-selectin, and leptin in obese women
      and men. In obese women, we also observed increased concentrations of C4 and
      decreased levels of adiponectin.

PMID- 22387154
TI  - Protective role of N-trans-feruloyltyramine against beta-amyloid peptide-induced
      neurotoxicity in rat cultured cortical neurons.
AB  - Enhanced oxidative stress and inflammation play important roles in the
      pathogenesis of Alzheimer's disease (AD). Amyloid beta-peptide (Abeta), a major
      component of amyloid plaques, is considered to have a causal role in the
      development and progress of AD by being the initiator of a pathological cascade
      leading to oxidative stress. The present study investigated the effect of N-trans
      feruloyltyramine (NTF) purified from Polyalthia suberosa, an alkaloid shown to
      protect against oxidative stress and cell death. Pre-treatment of rat primary
      cortical cell cultures with 25-250MUM NTF significantly attenuated 10MUM Abeta(1
      42)-induced neuronal death in a dose-dependent manner. Apoptotic cell death was
      demonstrated morphologically as well as by detection of the presence of activated
      caspase-3 and Bax, levels of which could be reduced by NTF pre-treatment. NTF
      also reduced production of reactive oxygen species induced by Abeta(1-42). These
      findings suggest that the protective effect of NTF against Abeta(1-42)-induced
      neuronal death might be due to its antioxidative property.

PMID- 22387155
TI  - Glutamate-induced free radical formation in rat brain synaptosomes is not
      dependent on intrasynaptosomal mitochondria membrane potential.
AB  - Glutamate induces reactive oxygen species formation (ROS) in neurons. Free
      radicals can potentially be synthesized by NADPH oxidase or mitochondria. The
      primary source of ROS origin has yet to be identified. In addition, pro-oxidant
      action of glutamate receptors on neuronal presynaptic terminals is still not
      characterized. We investigated the influence of glutamate and agonists of its
      ionotropic receptors on ROS formation detected by fluorescent dye DCFDA in rat
      brain synaptosomes. Glutamate in concentration 10 and 100MUM led to an increase
      of probe fluorescence pointing to free radical accumulation. This effect was
      mimicked by 100MUM of NMDA or 100MUM of kainate. Glutamate-induced ROS formation
      was sensitive to NMDA inhibitors MK-801 (10MUM), NO synthase (NOS) inhibitor l
      NAME (100MUM) and NADPH oxidase inhibitors DPI (30MUM) and not affected by
      mitochondrial uncoupler CCCP (10MUM) and mitochondrial toxins rotenone
      (10MUM)+oligomycin (5MUg/ml). We also showed that 100MUM of glutamate leads to a
      decrease of intrasynaptosomal mitochondrial potential monitored by fluorescent
      dye Rhodamine-123. Hence, the depolarization of intrasynaptosomal mitochondria is
      not a primary cause of glutamate-induced ROS formation in neuronal presynaptic
      terminals. Activation of NMDA receptors might be responsible for a certain part
      of glutamate pro-oxidant action. Most likely, sources of glutamate-induced ROS
      formation in neuronal presynaptic terminals are NADPH oxidase and NOS activation.

PMID- 22387156
TI  - Can vibrotactile working memory store multiple items?
AB  - Vibrotactile working memory is increasing in popularity as a model system to test
      theories of working memory. Notably, however, we know little about vibrotactile
      working memory capacity. While most other domains of working memory are able to
      store multiple items (for example, the seven-plus-or-minus-two capacity of verbal
      memory [17]), previous examinations of vibrotactile working memory suggest that
      stored items may suffer from high levels of interference in the form of
      overwriting or representation-based interference [2,4], potentially limiting
      capacity and also limiting our ability to draw comparisons between vibrotactile
      working memory and other forms of working memory. In the present study, we use a
      two-item delayed match-to-sample paradigm to demonstrate that subjects are able
      to store multiple items in vibrotactile working memory, suggesting that
      interference does not catastrophically limit capacity, and strengthening our
      ability to compare vibrotactile working memory to other working memory tasks.

PMID- 22387157
TI  - Action naming in Parkinson's disease patients on/off dopamine.
AB  - Growing evidence supports the notion that the same brain areas involved in
      planning and execution of movements are also involved in verb processing. Recent
      studies have pointed out the existence of verb impairment in patients with
      Parkinson's disease (PD), a neurodegenerative disorder typically characterized by
      motor disturbance related to dopamine deficiency in the nigrostriatal system. The
      aim of this study was to test the influence of dopaminergic treatment in a group
      of non-demented PD patients on the performance of action naming. The action
      pictures belonged to two categories: pictures with high and low degree of motor
      content. A group of 20 PD patients without dementia and 15 controls performed the
      task. PD patients were assessed twice, on and off medication, controls only once.
      A repeated measures ANOVA was carried out on the reaction times. The results
      showed a main effect of group and a significant interaction between group*motor
      content when comparing the three groups. When the comparison was made only on the
      PD groups (on vs. off medication) the interaction group*motor content was also
      significant, indicating that PD patients off medication had longer reaction times
      for pictures with a high degree of motor content compared to PD patients on
      medication. These results suggest a selective deficit in naming pictures
      associated with high motor content in PD patients without dopamine medication.
      This effect could be due to the relations between brain motor areas and verb
      processing associated with dopamine depletion.

PMID- 22387158
TI  - Apelin-13 microinjection into the paraventricular nucleus increased sympathetic
      nerve activity innervating brown adipose tissue in rats.
AB  - The aim of present study is to clarify the role of apelin in regulating energy
      homeostasis in brown adipose tissue (BAT). We examined the central effects of
      apelin-13 on the brain c-fos like immunoreactivity (c-FLI), BAT temperature and
      the activity of the sympathetic nerve activity innervating BAT in rats. In the
      hypothalamus, central infusion into the third cerebral ventricle (i3vt) of apelin
      13 caused induction of c-FLI in the paraventricular nucleus (PVN) compared with
      the controls (PBS-treated) group. In addition, microinjection of apelin-13 into
      the PVN produced significant increases in BAT temperature. Furthermore,
      microinjection of apelin-13 treatment increased BAT sympathetic nerve activity
      compared with controls. We conclude that apelin-13 microinjection into PVN
      increases sympathetic nerve activity innervating BAT.

PMID- 22387159
TI  - In vitro evaluation of intestinal fluoride absorption using different cell
      models.
AB  - The main routes of fluoride (F) exposure are drinking water and certain foods;
      consequently, intestinal absorption is an important stage in the study of F
      exposure. In the present study, different cell models [Caco-2, HT29-MTX and
      various proportions of Caco-2/HT29-MTX)] were used to evaluate intestinal
      transport of F. The influence of cell type, pH, mucus layer, bile salts and food
      matrices on the apparent permeability coefficient (P(app)) was evaluated. The
      results show that a higher proportion of HT29-MTX in the monolayer produces an
      increase in F permeability, although the mucus layer secreted by HT29-MTX
      decreases F transport. The results also show that taurocholic acid, a component
      of bile salts, and acid pH increase F permeability, whereas the presence of a
      food matrix (rice) decreases intestinal transport of F. In all cases, alterations
      in F permeability were closely related with modulation of cell junctions.

PMID- 22387160
TI  - Is the fear of dioxin cancer more harmful than dioxin?
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a proven animal carcinogen.
      Occupational cohorts with the highest exposures imply that there is a small risk
      of all cancers combined, but it is difficult to pinpoint the confounding effect
      of the main chemicals. Studies after major accidents do not unequivocally confirm
      this risk. The risks to populations at the current dioxin levels seem trivial if
      present at all. There is increasing evidence that the aryl hydrocarbon receptor
      (AhR), i.e. the so called "dioxin receptor", is a physiological transcription
      factor exerting important functions in the body. Consequently a certain level of
      AhR activation may be beneficial rather than harmful. This challenges the wisdom
      of excessive regulation of dioxin levels in certain foods and nutrients. This
      could pose indirect nutritional risks, in fact being more harmful than even the
      worst case predictions of the putative cancer risks attributable to dioxins.

PMID- 22387161
TI  - Antiinflammatory, analgesic and antioxidant activities of Cyathula prostrata
      (Linn.) Blume (Amaranthaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cyathula prostrata (Linn) Blume (Amaranthaceae)
      is an annual herb widely used traditionally in the treatment of various
      inflammatory and pain related health disorders in Nigeria. The aim of this study
      is to evaluate the anti-inflammatory, analgesic and antioxidant activities of the
      methanolic extract of Cyathula prostrata (Linn) Blume. MATERIALS AND METHODS: The
      anti-inflammatory (phorbol 12-myristate 13-acetate (PMA)-induced reactive oxygen
      species (ROS), lipopolysaccharide (LPS) induced nitric oxide production in U937
      macrophages, LPS-induced COX-2 expression, carrageenan-induced rat paw oedema,
      arachidonic acid-induced ear oedema and xylene-induced ear oedema), analgesic
      (acetic acid-induced writhing and hot plate tests) and antioxidant activities
      (DPPH [1,1-diphenyl-2-picrylhydrazyl] and lipid peroxidation assays) activities
      of the plant extract were investigated. RESULTS: The methanolic extract of
      Cyathula prostrata did not show inhibitory activity in the in vitro PMA-induced
      reactive oxygen species, LPS-induced nitric oxide production and LPS-induced COX
      2 expression assays. In the in vivo anti-inflammatory assays, the extract (50,
      100 and 200mg/kg) showed a significant (P<0.05) dose-dependent inhibition in the
      carrageenan, arachidonic acid and xylene-induced tests. Cyathula prostrata
      produced a significant (P<0.05, 0.001) dose-dependent inhibition in the acetic
      acid and hot plate analgesic tests respectively. The plant extract did not
      exhibit any antioxidant activity in the DPPH and lipid peroxidation assays.
      CONCLUSION: The results suggest that the methanolic extract of Cyathula prostrata
      possesses anti-inflammatory and analgesic activities and this authenticates the
      use of the plant in the traditional treatment of ailments associated with
      inflammation and pain.

PMID- 22387162
TI  - The dynamics of drug resistance: a mathematical perspective.
AB  - Resistance to chemotherapy is a key impediment to successful cancer treatment
      that has been intensively studied for the last three decades. Several central
      mechanisms have been identified as contributing to the resistance. In the case of
      multidrug resistance (MDR), the cell becomes resistant to a variety of
      structurally and mechanistically unrelated drugs in addition to the drug
      initially administered. Mathematical models of drug resistance have dealt with
      many of the known aspects of this field, such as pharmacologic sanctuary and
      location/diffusion resistance, intrinsic resistance, induced resistance and
      acquired resistance. In addition, there are mathematical models that take into
      account the kinetic/phase resistance, and models that investigate intracellular
      mechanisms based on specific biological functions (such as ABC transporters,
      apoptosis and repair mechanisms). This review covers aspects of MDR that have
      been mathematically studied, and explains how, from a methodological perspective,
      mathematics can be used to study drug resistance. We discuss quantitative
      approaches of mathematical analysis, and demonstrate how mathematics can be used
      in combination with other experimental and clinical tools. We emphasize the
      potential benefits of integrating analytical and mathematical methods into future
      clinical and experimental studies of drug resistance.

PMID- 22387163
TI  - Waiting time and pain during office hysteroscopy.
AB  - STUDY OBJECTIVE: To find a correlation between the waiting time between
      counseling about and performance of office hysteroscopy and the perception of
      pain. DESIGN: Observational study (Canadian Task Force classification II-2).
      SETTING: Academic environment. PATIENTS: Two hundred eighty-four women undergoing
      hysteroscopy. INTERVENTIONS: Diagnostic hysteroscopy with endometrial biopsy.
      MEASUREMENTS AND MAIN RESULTS: Before examination, patients were asked to
      complete 2 forms, the STAI-S (State-Trait Anxiety Inventory, State) and STAI-T
      (State-Trait Anxiety Inventory, Trait) anxiety scales, for evaluation of their
      usual anxiety state and their state of anxiety during the examination. Patients
      were asked to quantify on a visual analog scale the pain felt during the
      examination. A statistically significant positive correlation, even if weak, was
      demonstrated between pain and waiting time (r = 0.45; p < .01) but not with the
      values for the anxiety state (r = 0.06; p = .56) and anxiety trait (r = -0.05; p
      = .66). Pain (>=4) was significantly associated with waiting time (>=60 minutes)
      (odds ratio [OR], 5.21; 95% confidence interval [CI], 1.29-35.50), age (OR, 1.57;
      95% CI, 0.40-5.87) and menopause (OR, 2.81; 95% CI, 1.10-7.40) but not with STAI
      S level (>=34) (OR, 0.87; 95% CI, 0.26-3.12) or STAI-T level (>=34) (OR, 0.65;
      95% CI, 0.19-2.32). CONCLUSION: Office hysteroscopy is associated with a level of
      anxiety that can affect patient tolerability of the procedure. However, factors
      such as reducing waiting time may have a positive effect on patient compliance,
      making hysteroscopy easier and thereby increasing its diagnostic and therapeutic
      potential.

PMID- 22387164
TI  - Opposite and tissue-specific effects of coenzyme Q2 on mPTP opening and ROS
      production between heart and liver mitochondria: role of complex I.
AB  - Coenzyme Q(2) (CoQ(2)) is known to inhibit mitochondrial permeability transition
      pore (mPTP) opening in isolated rat liver mitochondria. In this study, we
      investigated and compared the effects of CoQ(2) on mPTP opening and ROS
      production in isolated rabbit heart and rat liver mitochondria. Mitochondria were
      isolated from New Zealand White rabbit hearts and Wistar rat livers. Oxygen
      consumption, Ca(2+)-induced mPTP opening, ROS production and NADH DUb-reductase
      activity were measured. Rotenone was used to investigate the effect of CoQ(2) on
      respiratory complex I activity. CoQ(2) (23 MUM) reduced the respiratory control
      index by 32% and 57% (p<0.01) in heart and liver mitochondria respectively,
      mainly through an increased oxygen consumption in state 4. CoQ(2) induced a 60%
      (p<0.05) decrease of calcium retention capacity (CRC) in heart mitochondria and
      inversely a 46% (p<0.05) increase in liver mitochondria. In basal condition,
      CoQ(2) induced a 170% (p<0.05) increase of H(2)O(2) production in heart
      mitochondria and 21% (ns) decrease of H(2)O(2) production in liver mitochondria.
      Because rotenone, a complex I inhibitor, increases H(2)O(2) production in heart
      but not in liver mitochondria we investigated the CoQ(2) effect in a dose
      response assay of complex I inhibition by rotenone in both mitochondria. CoQ(2)
      antagonized the effect of rotenone on respiratory complex I activity in liver but
      not in heart mitochondria. CoQ(2) significantly reduced NADH DUb-reductase
      activity in liver (-47%) and heart (-37%) mitochondria. In conclusion, our data
      showed that on the contrary to what was observed in liver mitochondria, CoQ(2)
      favors mPTP opening and ROS production in heart mitochondria through an opposite
      effect on respiratory complex I activity.

PMID- 22387165
TI  - Schizophrenia, neuroimaging and connectomics.
AB  - Schizophrenia is frequently characterized as a disorder of brain connectivity.
      Neuroimaging has played a central role in supporting this view, with nearly two
      decades of research providing abundant evidence of structural and functional
      connectivity abnormalities in the disorder. In recent years, our understanding of
      how schizophrenia affects brain networks has been greatly advanced by attempts to
      map the complete set of inter-regional interactions comprising the brain's
      intricate web of connectivity; i.e., the human connectome. Imaging connectomics
      refers to the use of neuroimaging techniques to generate these maps which,
      combined with the application of graph theoretic methods, has enabled relatively
      comprehensive mapping of brain network connectivity and topology in unprecedented
      detail. Here, we review the application of these techniques to the study of
      schizophrenia, focusing principally on magnetic resonance imaging (MRI) research,
      while drawing attention to key methodological issues in the field. The published
      findings suggest that schizophrenia is associated with a widespread and possibly
      context-independent functional connectivity deficit, upon which are superimposed
      more circumscribed, context-dependent alterations associated with transient
      states of hyper- and/or hypo-connectivity. In some cases, these changes in inter
      regional functional coupling dynamics can be related to measures of intra
      regional dysfunction. Topological disturbances of functional brain networks in
      schizophrenia point to reduced local network connectivity and modular structure,
      as well as increased global integration and network robustness. Some, but not
      all, of these functional abnormalities appear to have an anatomical basis, though
      the relationship between the two is complex. By comprehensively mapping
      connectomic disturbances in patients with schizophrenia across the entire brain,
      this work has provided important insights into the highly distributed character
      of neural abnormalities in the disorder, and the potential functional
      consequences that these disturbances entail.

PMID- 22387166
TI  - Cortical networks for vision and language in dyslexic and normal children of
      variable socio-economic status.
AB  - In dyslexia, anomalous activations have been described in both left temporo
      parietal language cortices and in left ventral visual occipito-temporal cortex.
      However, the reproducibility, task-dependency, and presence of these brain
      anomalies in childhood rather than adulthood remain debated. We probed the large
      scale organization of ventral visual and spoken language areas in dyslexic
      children using minimal target-detection tasks that were performed equally well by
      all groups. In 23 normal and 23 dyslexic 10-year-old children from two different
      socio-economic status (SES) backgrounds, we compared fMRI activity to visually
      presented houses, faces, and written strings, and to spoken sentences in the
      native or in a foreign language. Our results confirm a disorganization of both
      ventral visual and spoken language areas in dyslexic children. Visually, dyslexic
      children showed a normal lateral-to-medial mosaic of preferences, as well as
      normal responses to houses and checkerboards, but a reduced activation to words
      in the visual word form area (VWFA) and to faces in the right fusiform face area
      (FFA). Auditorily, dyslexic children exhibited reduced responses to speech in
      posterior temporal cortex, left insula and supplementary motor area, as well as
      reduced responses to maternal language in subparts of the planum temporale, left
      basal language area and VWFA. By correlating these two findings, we identify
      spoken-language predictors of VWFA activation to written words, which differ for
      dyslexic and normal readers. Similarities in fMRI deficits in both SES groups
      emphasize the existence of a core set of brain activation anomalies in dyslexia,
      regardless of culture, language and SES, without however resolving whether these
      anomalies are a cause or a consequence of impaired reading.

PMID- 22387168
TI  - The anterior left inferior frontal gyrus contributes to semantic unification.
AB  - Semantic unification, the process by which small blocks of semantic information
      are combined into a coherent utterance, has been studied with various types of
      tasks. However, whether the brain activations reported in these studies are
      attributed to semantic unification per se or to other task-induced concomitant
      processes still remains unclear. The neural basis for semantic unification in
      sentence comprehension was examined using event-related potentials (ERP) and
      functional Magnetic Resonance Imaging (fMRI). The semantic unification load was
      manipulated by varying the goodness of fit between a critical word and its
      preceding context (in high cloze, low cloze and violation sentences). The
      sentences were presented in a serial visual presentation mode. The participants
      were asked to perform one of three tasks: semantic congruency judgment (SEM),
      silent reading for comprehension (READ), or font size judgment (FONT), in
      separate sessions. The ERP results showed a similar N400 amplitude modulation by
      the semantic unification load across all of the three tasks. The brain
      activations associated with the semantic unification load were found in the
      anterior left inferior frontal gyrus (aLIFG) in the FONT task and in a widespread
      set of regions in the other two tasks. These results suggest that the aLIFG
      activation reflects a semantic unification, which is different from other brain
      activations that may reflect task-specific strategic processing.

PMID- 22387167
TI  - Evaluating reverse speech as a control task with language-related gamma activity
      on electrocorticography.
AB  - Reverse speech has often been used as a control task in brain-mapping studies of
      language utilizing various non-invasive modalities. The rationale is that reverse
      speech is comparable to forward speech in terms of auditory characteristics,
      while omitting the linguistic components. Thus, it may control for non-language
      auditory functions. This finds some support in fMRI studies indicating that
      reverse speech resulted in less blood-oxygen-level-dependent (BOLD) signal
      intensity in perisylvian regions than forward speech. We attempted to externally
      validate a reverse speech control task using intracranial electrocorticography
      (ECoG) in eight patients with intractable focal epilepsy. We studied adolescent
      and adult patients who underwent extraoperative ECoG prior to resective epilepsy
      surgery. All patients received an auditory language task during ECoG recording.
      Patients were presented 115 audible question stimuli, including 30 reverse speech
      trials. Reverse speech trials more strongly engaged bilateral superior temporal
      sites than did the corresponding forward speech trials. Forward speech trials
      elicited larger gamma-augmentation at frontal lobe sites not attributable to
      sensorimotor function. Other temporal and frontal sites of significant
      augmentation showed no significant difference between reverse and forward speech.
      Thus, we failed to validate reported evidence of weaker activation of temporal
      neocortices during reverse compared to forward speech. Superior temporal lobe
      engagement may indicate increased attention to reverse speech. Reverse speech
      does not appear to be a suitable task for the control of non-language auditory
      functions on ECoG.

PMID- 22387169
TI  - Spectrotemporal processing drives fast access to memory traces for spoken words.
AB  - The Mismatch Negativity (MMN) component of the event-related potentials is
      generated when a detectable spectrotemporal feature of the incoming sound does
      not match the sensory model set up by preceding repeated stimuli. MMN is enhanced
      at frontocentral scalp sites for deviant words when compared to acoustically
      similar deviant pseudowords, suggesting that automatic access to long-term memory
      traces for spoken words contributes to MMN generation. Does spectrotemporal
      feature matching also drive automatic lexical access? To test this, we recorded
      human auditory event-related potentials (ERPs) to disyllabic spoken words and
      pseudowords within a passive oddball paradigm. We first aimed at replicating the
      word-related MMN enhancement effect for Spanish, thereby adding to the available
      cross-linguistic evidence (e.g., Finnish, English). We then probed its resilience
      to spectrotemporal perturbation by inserting short (20 ms) and long (120 ms)
      silent gaps between first and second syllables of deviant and standard stimuli. A
      significantly enhanced, frontocentrally distributed MMN to deviant words was
      found for stimuli with no gap. The long gap yielded no deviant word MMN, showing
      that prior expectations of word form limits in a given language influence
      deviance detection processes. Crucially, the insertion of a short gap suppressed
      deviant word MMN enhancement at frontocentral sites. We propose that
      spectrotemporal point-wise matching constitutes a core mechanism for fast serial
      computations in audition and language, bridging sensory and long-term memory
      systems.

PMID- 22387171
TI  - Longitudinal change detection in diffusion MRI using multivariate statistical
      testing on tensors.
AB  - This paper presents a longitudinal change detection framework for detecting
      relevant modifications in diffusion MRI, with application to neuromyelitis optica
      (NMO) and multiple sclerosis (MS). The core problem is to identify image regions
      that are significantly different between two scans. The proposed method is based
      on multivariate statistical testing which was initially introduced for tensor
      population comparison. We use this method in the context of longitudinal change
      detection by considering several strategies to build sets of tensors
      characterizing the variability of each voxel. These strategies make use of the
      variability existing in the diffusion weighted images (thanks to a bootstrap
      procedure), or in the spatial neighborhood of the considered voxel, or a
      combination of both. Results on synthetic evolutions and on real data are
      presented. Interestingly, experiments on NMO patients highlight the ability of
      the proposed approach to detect changes in the normal-appearing white matter
      (according to conventional MRI) that are related with physical status outcome.
      Experiments on MS patients highlight the ability of the proposed approach to
      detect changes in evolving and non-evolving lesions (according to conventional
      MRI). These findings might open promising prospects for the follow-up of NMO and
      MS pathologies.

PMID- 22387170
TI  - Across-study and within-subject functional connectivity of a right temporo
      parietal junction subregion involved in stimulus-context integration.
AB  - Bidirectional integration between sensory stimuli and contextual framing is
      fundamental to action control. Stimuli may entail context-dependent actions,
      while temporal or spatial characteristics of a stimulus train may establish a
      contextual framework for upcoming stimuli. Here we aimed at identifying core
      areas for stimulus-context integration and delineated their functional
      connectivity (FC) using meta-analytic connectivity modeling (MACM) and analysis
      of resting-state networks. In a multi-study conjunction, consistently increased
      activity under higher demands on stimulus-context integration was predominantly
      found in the right temporo-parietal junction (TPJ), which represented the largest
      cluster of overlap and was thus used as the seed for the FC analyses. The
      conjunction between task-dependent (MACM) and task-free (resting state) FC of the
      right TPJ revealed a shared network comprising bilaterally inferior parietal and
      frontal cortices, anterior insula, premotor cortex, putamen and cerebellum, i.e.,
      a 'ventral' action/attention network. Stronger task-dependent (vs. task-free)
      connectivity was observed with the pre-SMA, dorsal premotor cortex, intraparietal
      sulcus, basal ganglia and primary sensori motor cortex, while stronger resting
      state (vs. task-dependent) connectivity was found with the dorsolateral
      prefrontal and medial parietal cortex. Our data provide strong evidence that the
      right TPJ may represent a key region for the integration of sensory stimuli and
      contextual frames in action control. Task-dependent associations with regions
      related to stimulus processing and motor responses indicate that the right TPJ
      may integrate 'collaterals' of sensory processing and apply (ensuing) contextual
      frames, most likely via modulation of preparatory loops. Given the pattern of
      resting-state connectivity, internal states and goal representations may provide
      the substrates for the contextual integration within the TPJ in the absence of a
      specific task.

PMID- 22387172
TI  - Stimulus repetition probability effects on repetition suppression are position
      invariant for faces.
AB  - It has been shown that the probability of face repetitions influences the
      magnitude of repetition-related response reductions (Summerfield et al., 2008),
      implying that perceptual expectations affect adaptation and repetition
      suppression processes in the human central nervous system. An unresolved question
      is whether probability effects are specific for the retinal position of the
      stimuli or affect stimulus processing globally, throughout the visual field. To
      address this question we tested whether face repetition probability affects fMRI
      adaptation (fMRIa) when the repeated stimuli are presented on the same retinal
      position, overlapping each other or when they are presented in opposite
      hemifields. Subjects were exposed to either two identical (repeated trial, RT) or
      two different (alternating trial, AT) face stimuli. Both types of trials were
      presented either in blocks consisting of 75% (repeated block, RB) or 25%
      (alternating block, AB) of RTs. We found that repetition probability influences
      fMRIa equally for overlapping and nonoverlapping arrangements: the signal
      reduction after RT was more pronounced in RB than in AB for both spatial
      arrangements of stimulus-pairs. This effect was present in bilateral fusiform and
      occipital face areas, as well as in the lateral occipital cortex. Our results
      support the role of stimulus repetition probability in determining fMRIa and
      shows that the effect is invariant to the retinal position of stimuli.

PMID- 22387173
TI  - Quantitative evaluation of white matter tract DTI parameter changes in gliomas
      using nonlinear registration.
AB  - Diffusion tensor imaging (DTI) has been used extensively to investigate white
      matter architecture in the brain. In the context of neurological disease,
      quantification of DTI data sets enables objective characterisation of the
      associated pathological changes. The aim of this study is to propose a method of
      evaluating DTI parameter changes in gliomas in the internal capsule using
      nonlinear registration to delineate the white matter and enable quantitative
      assessment of DTI derived parameters. 20 patients selected pre-operatively with
      probable grade 2 or grade 3 glioma on structural MRI along with ten normal
      volunteers were included in this study. DTI fractional anisotropy (FA) maps were
      used to define a common segmented FA skeleton that was projected back onto the
      original individual FA maps. Objective segment classification as normal or
      abnormal was achieved by comparison to prediction intervals of FA and mean
      diffusivity (MD) defined in normal subjects. The internal capsules of each
      patient were segmented into 10 regions of interest (ROI) with 20 and 16 segments
      across the group having significantly increased or decreased FA and MD values
      respectively. Seven glioma patients had abnormal DTI parameters in the internal
      capsule. We show that the classification of tract segments was consistent with
      disruption, oedema or compression. The results suggest that this method could be
      used to detect changes in eloquent white matter tracts in individual patients.

PMID- 22387175
TI  - Multi-stage segmentation of white matter hyperintensity, cortical and lacunar
      infarcts.
AB  - Cerebral abnormalities such as white matter hyperintensity (WMH), cortical
      infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently
      present in patients with stroke and dementia. Up to date, there are limited
      algorithms available to automatically delineate these cerebral abnormalities
      partially due to their complex appearance in MR images. In this paper, we
      describe an automated multi-stage segmentation approach for labeling the WMH, CI,
      and LI using multi-modal MR images. We first automatically segment brain tissues
      (white matter, gray matter, and CSF) based on the T1-weighted image and then
      identify hyperintense voxels based on the fluid attenuated inversion recovery
      (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2
      weighted, and FLAIR images. The segmentation accuracy is evaluated using a
      community-based sample of 272 old adults. Our results show that the automated
      segmentation of the WMH, CI, and LI is comparable with manual labeling in terms
      of spatial location, volume, and the number of lacunes. Additionally, the WMH
      volume is highly correlated with the visual grading score based on the Age
      Related White Matter Changes (ARWMC) protocol. The evaluations against the manual
      labeling and ARWMC visual grading suggest that our algorithm provides reasonable
      segmentation accuracy for the WMH, CI, and LI.

PMID- 22387174
TI  - Catechol-O-methyltransferase gene variation: impact on amygdala response to
      aversive stimuli.
AB  - The functional catechol-O-methyltransferase (COMT) val158met polymorphism has
      been found to be associated with anxiety disorders and depression as well as with
      neural correlates of emotional processing, with, however, contradictory results.
      Thus, the aim of the present study was to re-evaluate the impact of the COMT
      val158met variant on neural activation correlates of emotional face processing in
      a sample of healthy probands. In 85 healthy subjects genotyped for the COMT
      val158met polymorphism, amygdala responses were assessed by means of fMRI.
      Participants were presented with anger- and fear-relevant faces in a robust
      emotion-processing paradigm. For exploratory reasons, a supplementary whole-brain
      analysis of the allele-dose model and a gender-stratified analysis were
      conducted. The COMT 158val allele showed an allele-dose effect on increased
      predominantly left-sided amygdala activity in response to fearful/angry facial
      stimuli (p(uncorrected)=.00004). This effect was independent from the
      distribution of the frequently studied 5-HTTLPR polymorphism for which a linear
      effect of S-alleles on amygdala responsiveness was replicated. The influence of
      COMT 158val alleles was only discerned in the female subgroup of probands. The
      whole-brain analysis suggested associations of the COMT 158val allele with
      increased activity in areas of the ventral visual stream and the lateral
      prefrontal cortex. The present results provide further support for a-potentially
      female-specific-role of the COMT val158met polymorphism in the genetic and neural
      underpinnings of anxiety- and depression-related intermediate phenotypes and may
      aid in further clarifying the differential role of COMT genotype driven
      dopaminergic tonus in the processing of emotionally salient stimuli.

PMID- 22387176
TI  - PPARdelta prevents radiation-induced proinflammatory responses in microglia via
      transrepression of NF-kappaB and inhibition of the PKCalpha/MEK1/2/ERK1/2/AP-1
      pathway.
AB  - Partial or whole-brain irradiation is often required to treat both primary and
      metastatic brain cancer. Radiation-induced normal tissue injury, including
      progressive cognitive impairment, however, can significantly affect the well
      being of the approximately 200,000 patients who receive these treatments each
      year in the United States. Although the exact mechanisms underlying radiation
      induced late effects remain unclear, oxidative stress and inflammation are
      thought to play a critical role. Microglia are key mediators of
      neuroinflammation. Peroxisomal proliferator-activated receptor (PPAR) delta has
      been shown to be a potent regulator of anti-inflammatory responses. Thus, we
      hypothesized that PPARdelta activation would modulate the radiation-induced
      inflammatory response in microglia. Incubating BV-2 murine microglial cells with
      the PPARdelta agonist L-165041 prevented the radiation-induced increase in: (i)
      intracellular reactive oxygen species generation, (ii) Cox-2 and MCP-1
      expression, and (iii) IL-1beta and TNF-alpha message levels. This occurred, in
      part, through PPARdelta-mediated modulation of stress-activated kinases and
      proinflammatory transcription factors. PPARdelta inhibited NF-kappaB via
      transrepression by physically interacting with the p65 subunit and prevented
      activation of the PKCalpha/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation
      induced increase in intracellular reactive oxygen species generation. These data
      support the hypothesis that PPARdelta activation can modulate radiation-induced
      oxidative stress and inflammatory responses in microglia.

PMID- 22387177
TI  - NRF2 inhibition represses ErbB2 signaling in ovarian carcinoma cells:
      implications for tumor growth retardation and docetaxel sensitivity.
AB  - NF-E2-related factor 2 (NRF2) is a transcription factor that regulates the
      expression of various antioxidant and detoxifying enzymes. Although the benefit
      of NRF2 in cancer prevention is well established, its role in cancer pathobiology
      was recently discovered. In this study, the role of NRF2 in tumor growth and
      docetaxel sensitivity was investigated in ErbB2-overexpressing ovarian carcinoma
      SKOV3 cells. Interfering RNA-mediated stable inhibition of NRF2 in SKOV3 cells
      repressed NRF2 signaling, resulting in cell growth arrest at G(0)/G(1) phase and
      tumor growth retardation in mouse xenografts. Microarray analysis revealed that
      ErbB2 expression is substantially reduced in NRF2-inhibited SKOV3 and this was
      further confirmed by RT-PCR and immunoblot analysis. Repression of ErbB2 led to a
      decrease in phospho-AKT and enhanced p27 protein, reinforcing the effect of NRF2
      knockdown on SKOV3 growth. Furthermore, NRF2 inhibition-mediated ErbB2 repression
      increases the sensitivity of these cells to docetaxel cytotoxicity and apoptosis.
      The linkage between NRF2 and ErbB2 was confirmed in the ErbB2-positive breast
      cancer cell line BT-474: NRF2 knockdown suppressed ErbB2 expression and enhanced
      docetaxel sensitivity. Our results provide insight into the coordinated
      regulation of signaling molecules responding to environmental stress and suggest
      that NRF2 modulation might be a therapeutic strategy to limit tumor growth and
      enhance sensitivity to taxane-based chemotherapy.

PMID- 22387178
TI  - Methionine excess in diet induces acute lethal hepatitis in mice lacking
      cystathionine gamma-lyase, an animal model of cystathioninuria.
AB  - Physiological roles of the transsulfuration pathway have been recognized by its
      contribution to the synthesis of cytoprotective cysteine metabolites, such as
      glutathione, taurine/hypotaurine, and hydrogen sulfide (H(2)S), whereas its roles
      in protecting against methionine toxicity remained to be clarified. This study
      aimed at revealing these roles by analyzing high-methionine diet-fed
      transsulfuration-defective cystathionine gamma-lyase-deficient (Cth(-/-)) mice.
      Wild-type and Cth(-/-) mice were fed a standard diet (1 * Met: 0.44%) or a high
      methionine diet (3 * Met or 6 * Met), and hepatic conditions were monitored by
      serum biochemistry and histology. Metabolome analysis was performed for
      methionine derivatives using capillary electrophoresis- or liquid chromatography
      mass spectrometry and sulfur-detecting gas chromatography. The 6 * Met-fed Cth(-/
      ) (not 1 * Met-fed Cth(-/-) or 6 * Met-fed wild type) mice displayed acute
      hepatitis, which was characterized by markedly elevated levels of serum
      alanine/aspartate aminotransferases and serum/hepatic lipid peroxidation,
      inflammatory cell infiltration, and hepatocyte ballooning; thereafter, they died
      of gastrointestinal bleeding due to coagulation factor deficiency. After 1 week
      on 6 * Met, blood levels of ammonia/homocysteine and hepatic levels of
      methanethiol/3-methylthiopropionate (a methionine transamination
      product/methanethiol precursor) became significantly higher in Cth(-/-) mice than
      in wild-type mice. Although hepatic levels of methionine sulfoxide became higher
      in 6 * Met-fed wild-type mice and Cth(-/-) mice, those of glutathione,
      taurine/hypotaurine, and H(2)S became lower and serum levels of homocysteine
      became much higher in 6 * Met-fed Cth(-/-) mice than in wild-type mice. Thus,
      transsulfuration plays a critical role in the detoxification of excessive
      methionine by circumventing aberrant accumulation of its toxic transamination
      metabolites, including ammonia, methanethiol, and 3-methylthiopropionate, in
      addition to synthesizing cysteine-derived antioxidants to counteract accumulated
      pro-oxidants such as methionine sulfoxide and homocysteine.

PMID- 22387179
TI  - p53 at the crossroads between cancer and neurodegeneration.
AB  - Aging, dementia, and cancer share a critical set of altered cellular functions in
      response to DNA damage, genotoxic stress, and other insults. Recent data suggest
      that the molecular machinery involved in maintaining neural function in
      neurodegenerative disease may be shared with oncogenic pathways. Cancer and
      neurodegenerative diseases may be influenced by common signaling pathways
      regulating the balance of cell survival versus death, a decision often governed
      by checkpoint proteins. This paper focuses on one such protein, p53, which
      represents one of the most extensively studied proteins because of its role in
      cancer prevention and which, furthermore, has been recently shown to be involved
      in aging and Alzheimer disease (AD). The contribution of a conformational change
      in p53 to aging and neurodegenerative processes has yet to be elucidated. In this
      review we discuss the multiple functions of p53 and how these correlate between
      cancer and neurodegeneration, focusing on various factors that may have a role in
      regulating p53 activity. The observation that aging and AD interfere with
      proteins controlling duplication and cell cycle may lead to the speculation that,
      in senescent neurons, aberrations in proteins generally dealing with cell cycle
      control and apoptosis could affect neuronal plasticity and functioning rather
      than cell duplication.

PMID- 22387180
TI  - ATP-dependent potassium channel blockade strengthens microglial neuroprotection
      after hypoxia-ischemia in rats.
AB  - Stroke causes CNS injury associated with strong fast microglial activation as
      part of the inflammatory response. In rat models of stroke, sulphonylurea
      receptor blockade with glibenclamide reduced cerebral edema and infarct volume.
      We postulated that glibenclamide administered during the early stages of stroke
      might foster neuroprotective microglial activity through ATP-sensitive potassium
      (K(ATP)) channel blockade. We found in vitro that BV2 cell line showed
      upregulated expression of K(ATP) channel subunits in response to pro-inflammatory
      signals and that glibenclamide increases the reactive morphology of microglia,
      phagocytic capacity and TNFalpha release. Moreover, glibenclamide administered to
      rats 6, 12 and 24h after transient Middle Cerebral Artery occlusion improved
      neurological outcome and preserved neurons in the lesioned core three days after
      reperfusion. Immunohistochemistry with specific markers to neuron, astroglia,
      microglia and lymphocytes showed that resident amoeboid microglia are the main
      cell population in that necrotic zone. These reactive microglial cells express
      SUR1, SUR2B and Kir6.2 proteins that assemble in functional K(ATP) channels.
      These findings provide that evidence for the key role of K(ATP) channels in the
      control of microglial reactivity are consistent with a microglial effect of
      glibenclamide into the ischemic brain and suggest a neuroprotective role of
      microglia in the early stages of stroke.

PMID- 22387181
TI  - Development of clinical trial protocols involving advanced radiation therapy
      techniques: the European Organisation for Research and Treatment of Cancer
      Radiation Oncology Group approach.
AB  - The European Organisation for Research and Treatment of Cancer (EORTC) Master
      Protocol for phase III radiation therapy (RT) studies was published in 1995 to
      define in a consistent sequence the parameters which must be addressed when
      designing a phase III trial 'from the rationale to the references'. This was
      originally implemented to assist study investigators and writing committees, and
      to increase homogeneity within Radiation Oncology Group (ROG) study protocols.
      However, RT planning, delivery, treatment verification and quality assurance (QA)
      have evolved significantly over the last 15 years and clinical trial protocols
      must reflect these developments. The goal of this update is to describe the
      incorporation of these developments into the EORTC-ROG protocol template.
      Implementation of QA procedures for advanced RT trials is also briefly described
      as these essential elements must also be clearly articulated. This guide may
      assist both investigators participating in current ROG trials and others involved
      in writing an advanced RT trial protocol.

PMID- 22387182
TI  - Successful centralisation of patients with vulvar carcinoma: a population-based
      study in The Netherlands.
AB  - INTRODUCTION: In general, centralisation of care for patients with rare
      malignancies is advised in order to improve outcome with respect to prognosis and
      treatment related morbidity. Therefore, centralisation of women with vulvar
      squamous cell carcinoma (SCC), which is an extremely rare tumour, has been
      advocated by the national guidelines of the Dutch Society of Obstetrics and
      Gynaecology in 2000. The objective of this study was to determine whether this
      advice has been adapted and has led to improved survival. METHODS: All patients
      diagnosed with vulvar malignancies between 1989 and 2008 in the Eastern part of
      the Netherlands were retrieved from the population-based cancer registry held by
      the Comprehensive Cancer Centre, The Netherlands. Patient- and tumour
      characteristics and vital status until January 2011 were retrieved. Data of
      patients diagnosed in two periods (before and after release of the guideline;
      1989-1999 and 2000-2008) were compared. Relative survival rates were calculated
      as a good approximation of cause-specific survival. RESULTS: A total number of
      382 patients with vulvar SCC with invasion > 1mm, who had an indication for groin
      surgery, were included in the analysis. In the first decade 62% (123 of 198
      patients) were treated in a specialised oncology centre, which increased to 93%
      (172 of 184 patients) in the more recent period. Overall, the 5 year relative
      survival improved slightly from 69% (95% confidence interval (CI) 60-77%) to 75%
      (95% CI 65-83%). After adjustment for age and stage, being treated in a
      specialised oncology centre was an independent prognostic factor for survival.
      CONCLUSION: Centralisation of care for vulvar SCC patients has been well adopted
      in the Eastern part of the Netherlands. Being treated in a specialised oncology
      centre was associated with a better survival after adjustment for age and stage.

PMID- 22387183
TI  - PTSD factor structure differences between veterans with and without a PTSD
      diagnosis.
AB  - This study examined differences in posttraumatic stress disorder's (PTSD) factor
      structure between veterans with and without a PTSD diagnosis. An archival dataset
      of 378 trauma-exposed Canadian veterans (mostly men) was used. The sample was
      divided into participants who met DSM-IV criteria for PTSD (n=230) and those who
      did not (n=148), based on a structured diagnostic interview. Confirmatory factor
      analysis was conducted to determine which empirically supported four-factor PTSD
      model best fit the data: (1) King, Leskin, King, and Weathers' (1998) Emotional
      Numbing model of Reexperiencing, Avoidance, Emotional Numbing and Hyperarousal
      factors, or (2) Simms, Watson, and Doebbeling's (2002) Dysphoria model of
      Reexperiencing, Avoidance, Dysphoria, and Hyperarousal factors. Results indicated
      that both models fit slightly better in the No-PTSD group. A series of
      measurement invariance tests demonstrated that the two groups varied on all
      parameters with the exception of factor loadings. The PTSD-group had larger
      intercepts, factor means, and residual error variance, suggesting that these
      participants had greater PTSD severity but more measurement error associated with
      their PTSD ratings. This study contributes to our understanding of how a PTSD
      diagnosis impacts the structure of PTSD symptoms at the latent level.

PMID- 22387184
TI  - Participatory Training Evaluation Method (PATEM) as a collaborative evaluation
      capacity building strategy.
AB  - This article describes Participatory Training Evaluation Method (PATEM) of
      measuring participants' reaction to the training. PATEM provides rich
      information; allows to document evaluation findings; becomes organic part of the
      training that helps participants process their experience individually and as a
      group; makes sense to participants; is an interesting and exciting group
      activity; becomes a part of the learning process; is flexible enough to
      accommodate what are often dynamic and less-than-predictable training contexts;
      and can be used in groups of various sizes. The article includes step-by-step
      instructions on how to use PATEM and illustrative examples of participants'
      feedback.

PMID- 22387185
TI  - Identifying malignant transformations in recurrent low grade gliomas using high
      resolution magic angle spinning spectroscopy.
AB  - OBJECTIVE: The objective of this study was to determine whether metabolic
      parameters derived from ex vivo analysis of tissue samples are predictive of
      biologic characteristics of recurrent low grade gliomas (LGGs). This was achieved
      by exploring the use of multivariate pattern recognition methods to generate
      statistical models of the metabolic characteristics of recurrent LGGs that
      correlate with aggressive biology and poor clinical outcome. METHODS: Statistical
      models were constructed to distinguish between patients with recurrent gliomas
      that had undergone malignant transformation to a higher grade and those that
      remained grade 2. The pattern recognition methods explored in this paper include
      three filter-based feature selection methods (chi-square, gain ratio, and two-way
      conditional probability), a genetic search wrapper-based feature subset selection
      algorithm, and five classification algorithms (linear discriminant analysis,
      logistic regression, functional trees, support vector machines, and decision
      stump logit boost). The accuracy of each pattern recognition framework was
      evaluated using leave-one-out cross-validation and bootstrapping. MATERIALS: The
      population studied included fifty-three patients with recurrent grade 2 gliomas.
      Among these patients, seven had tumors that transformed to grade 4, twenty-four
      had tumors that transformed to grade 3, and twenty-two had tumors that remained
      grade 2. Image-guided tissue samples were obtained from these patients using
      surgical navigation software. Part of each tissue sample was examined by a
      pathologist for histological features and for consistency with the tumor grade
      diagnosis. The other part of the tissue sample was analyzed with ex vivo nuclear
      magnetic resonance (NMR) spectroscopy. RESULTS: Distinguishing between recurrent
      low grade gliomas that transformed to a higher grade and those that remained
      grade 2 was achieved with 96% accuracy, using areas of the ex vivo NMR spectrum
      corresponding to myoinositol, 2-hydroxyglutarate, hypo-taurine, choline,
      glycerophosphocholine, phosphocholine, glutathione, and lipid. Logistic
      regression and decision stump boosting models were able to distinguish between
      recurrent gliomas that transformed to a higher grade and those that did not with
      100% training accuracy (95% confidence interval [93-100%]), 96% leave-one-out
      cross-validation accuracy (95% confidence interval [87-100%]), and 96%
      bootstrapping accuracy (95% confidence interval [95-97%]). Linear discriminant
      analysis, functional trees, and support vector machines were able to achieve
      leave-one-out cross-validation accuracy above 90% and bootstrapping accuracy
      above 85%. The three feature ranking methods were comparable in performance.
      CONCLUSIONS: This study demonstrates the feasibility of using quantitative
      pattern recognition methods for the analysis of metabolic data from brain tissue
      obtained during the surgical resection of gliomas. All pattern recognition
      techniques provided good diagnostic accuracies, though logistic regression and
      decision stump boosting slightly outperform the other classifiers. These methods
      identified biomarkers that can be used to detect malignant transformations in
      individual low grade gliomas, and can lead to a timely change in treatment for
      each patient.

PMID- 22387186
TI  - Identifying a small set of marker genes using minimum expected cost of
      misclassification.
AB  - OBJECTIVES: This paper presents a model independent feature selection approach to
      identify a small subset of marker genes. METHODS AND MATERIAL: An evaluation
      measure, minimum expected cost of misclassification (MEMC), is used to estimate
      the discriminative power of a feature subset without building a model. The MECM
      measure is combined with sequential forward search for feature selection. This
      approach was applied to a breast cancer profiling problem, with the goal of
      identifying a small number of marker genes whose expression can be used to
      predict cancer molecular subtype (p53 gene status). Furthermore, the method was
      also applied to find a small set of single-nucleotide polymorphisms (SNPs) that
      can be used to predict molecular phenotype of a different type, namely alleles
      (genetic variants) of human leukocyte antigen genes that play an important roles
      in autoimmunity. RESULTS: Two marker genes were identified based on p53 status,
      which achieved a p-value of 7.53*10(-5) (vs. 6*10(-4) with 32 genes identified by
      previous research) in survival analysis. Six SNP loci were identified that
      achieved a leave-one-out cross-validation accuracy of 92.8% (vs. 90.6% and 89.5%
      with 18 SNPs selected using chi2 statistics and information gain, respectively).
      CONCLUSION: The MECM-based feature selection approach is capable of identifying a
      smaller subset of market genes with comparable or even better performance than
      that obtained using conventional filter methods.

PMID- 22387187
TI  - Construction of a native promoter-containing transposon vector for the stable
      monitoring of the denitrifying bacterium Pseudomonas stutzeri LYS-86 by
      chromosomal-integrated gfp.
AB  - Green fluorescent protein (GFP) is the most potential useful marker for the in
      situ monitoring of biofilm microbes. The objective of this study was to construct
      and compare the efficacy of transposon vectors containing native and foreign
      promoters in monitoring the denitrifying bacterium Pseudomonas stutzeri LYS-86 by
      chromosomal-integrated gfp. The promoter of nitrite reductase (Pnir) was cloned
      from LYS-86 and utilized to construct the transposon vector pUT/mini-Tn5-km2-Pnir
      gfp. Another transposon vector, pUT/mini-Tn5-km2-Plac-gfp, containing the lactose
      promoter Plac was also constructed. These two transposon vectors and pUT-luxAB
      gfp containing the promoter PpsbA were individually inserted into the chromosome
      of P. stutzeri LYS-86 by conjugation. Three GFP-tagged recombinant strains, LYS
      Plac-gfp, LYS-Pnir-gfp, and LYS-PpsbA-gfp, were selected from the conjugants.
      Green fluorescence was observed only in LYS-Pnir-gfp, suggesting that the native
      promoter Pnir may be more suitable for GFP expression in P. stutzeri than the
      foreign promoters Plac and PpsbA. Indeed, LYS-Pnir-gfp maintained stable GFP
      fluorescence over 16 subcultures without significant changes in the denitrifying
      capacity.

PMID- 22387188
TI  - Occurrence and persistence of organic emerging contaminants and priority
      pollutants in five sewage treatment plants of Spain: two years pilot survey
      monitoring.
AB  - This work summarized all results obtained during almost two-years of a monitoring
      programme carried out in five municipal sewage treatment plants (STPs) located in
      the north, centre and south-east of Spain. The study evaluated the occurrence and
      persistence of a group of 100 organic compounds belonging to several chemical
      groups (pharmaceuticals, personal care products, pesticides and metabolites). The
      average removal efficiencies of the STPs studied varied from 20% (erythromycin)
      to 99% (acetaminophen). In analysed samples, we identified a large number of
      compounds at mean range concentrations between 7-59,495 ng/L and 5-32,720 ng/L
      for influent and effluent samples, respectively. This study also identified 20 of
      the mostly detected and persistent compounds in wastewater effluent, of which
      hydrochlorothiazide, atenolol, gemfibrozil, galaxolide and three metabolites
      (fenofibric acid, 4-AAA and 4-FAA), presented the highest average contribution
      percentages, in relation to the total load of contaminants for the different STPs
      effluent studied.

PMID- 22387189
TI  - Expanding character sampling for the molecular phylogeny of euplotid ciliates
      (Protozoa, Ciliophora) using three markers, with a focus on the family
      Uronychiidae.
AB  - Although euplotida ciliates are widely used as model organisms in multiple fields
      of biology, details of their phylogenetic relationships remain unresolved despite
      a rich history of investigation with small subunit (SSU) rDNA sequences and other
      characters. Here, six genera in Diophrys-like complex and three other euplotid
      genera are sampled for SSU-rDNA, ITS1-5.8S-ITS2 and LSU-rDNA, and their
      phylogenies were inferred with unconstrained and constrained analyses. In
      general, the concatenated analyses infer more reliable, less ambiguous
      phylogenies with higher node support values. The following conclusions can be
      made: (1) four well-supported clades are consistently detected in the family
      Uronychiidae, forming into two subgroups, which challenge the traditional
      arrangement based on morphological similarities; (2) the subfamily Diophryinae is
      paraphyletic; (3) the monophyly of Paradiophrys and the establishment of
      Apodiophrys and Diophryopsis is fully supported by concatenated data; (4)
      Apodiophrys and Paradiophrys form independent lineages, at the subfamily level,
      from other Diophrys-like genera; and (5) the highly specialized Pseudodiophrys
      nests within Diophrys.

PMID- 22387191
TI  - Group reflections on building academic geriatric nursing capacity.

PMID- 22387190
TI  - Medication beliefs and antihypertensive adherence among older adults: a pilot
      study.
AB  - Older adults with hypertension are dependent on medication to control blood
      pressure and reduce risk for cardiovascular disease and renal impairment.
      Unfortunately, adherence to antihypertensive regimens remains low. This pilot
      study examines the relation among medication beliefs, demographic variables, and
      antihypertensive medication adherence in a sample of older adults (median age =
      74 years). Medication beliefs were measured using the Beliefs About Medicines
      Questionnaire (BMQ), and medication adherence was measured by electronic
      monitoring. Among study participants (n = 33), concerns about medications were
      found to be related to poorer antihypertensive adherence. In particular, older
      adults with lower medication adherence were concerned about dependency and long
      term effects from their medications. When controlling for other factors that may
      influence antihypertensive adherence, beliefs about medication necessity were
      related to adherence (odds ratio: 2.027, 95% confidence interval: 1.10-3.75).

PMID- 22387192
TI  - Functional status in older women following gynecological cancer surgery: can
      choice of measure influence evidence for clinical practice?
AB  - Although functional status serves as a major predictor of morbidity, researchers
      and clinicians use different terms and measures, limiting comparisons across
      studies. To demonstrate how differing measures may generate varied findings, we
      compared and contrasted data from the SF-12 Health Survey Physical Component
      Summary Scale (SF-12 PCS) and the Enforced Social Dependency Scale (ESDS). The
      sample consisted of 49 women aged 65 and older recovering from gynecological
      cancer surgery with data collection at baseline (postoperative period) and then
      at 3 and 6 months. Analysis of the relationship between SF-12 PCS and ESDS over
      time using generalized estimating equations (GEE) demonstrated the relationship
      was less than 1.0, signaling less than perfect agreement between measures (beta =
      0.16, P = .002). These findings suggest that that the 2 measures are not
      interchangeable and may produce conflicting evidence. This highlights the
      importance of researchers' and clinicians' careful conceptualization and
      operationalization of functional status before measure selection.

PMID- 22387193
TI  - [Surgery and postoperative radiation therapy in primary retroperitoneal sarcomas:
      experience of the cancer centre Alexis-Vautrin].
AB  - PURPOSE: Surgical resection remains the standard treatment for patients with
      resectable retroperitoneal sarcomas. The aim of this study was to retrospectively
      analyse the outcomes of patients with primary retroperitoneal sarcoma. PATIENTS
      AND METHODS: We analysed data of 50 patients with primary retroperitoneal sarcoma
      who underwent curative-intent resection from 1975 to 2008. External beam
      radiotherapy and chemotherapy were delivered postoperatively. Demographics,
      surgical, pathological variables and chemo/radiation therapy were analysed as
      prognosis factors. RESULTS: There were 22 males and 28 females (mean age 54 +/-
      13 years). Surgery required visceral resections in 30 patients. There were 16
      leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients
      had clear surgical margins. Twenty-eight patients received postoperative external
      beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the
      follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1
      resection group (n=36). Postoperative external beam radiotherapy tends to
      increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05).
      The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years,
      respectively. Although R0 resection (P=0.01), well tumour differentiation
      (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly
      influenced overall survival in univariate analysis, only R0 resection was an
      independent prognostic factor in a multivariate analysis. CONCLUSION: We confirm
      the pre-eminence of radical surgery with negative margins as major prognostic
      factor and the benefit of postoperative radiotherapy.

PMID- 22387194
TI  - [Outcome of cervical carcinoma with locoregional lymph node involvement by FDG
      PET].
AB  - PURPOSE: To assess the outcome of cervical carcinoma with positive nodes on
      fluorodesoxyglucose positon emission tomography scans (FDG-PET). PATIENTS AND
      METHODS: Patients with cervical carcinoma who had pelvic and/or para-aortic lymph
      nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007
      were retrospectively studied. All patients received pelvic (and possibly para
      aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly
      surgery. The first site of relapse was classified as follows: local, nodal
      (pelvic or para-aortic) or metastatic. RESULTS: Forty patients were included the
      study. Median age was 47 years (range: 28-78). Thirty patients had nodal
      involvement limited to pelvic area and ten had a para-aortic involvement. Median
      follow-up was 42.5 months (range: 11-85). There were 22 relapses and 20 deaths:
      20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 %
      confidence interval [CI]: 36-65). First relapse was: metastatic for 33 % (13/40),
      local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis
      has revealed that only staging according to International Federation of
      Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant
      impact on survival. Three-year survival was 58 % (CI: 39-74) and 24 % (CI: 7-57)
      (P=0.009) in patient without and with para-aortic involvement, respectively.
      CONCLUSION: Para-aortic involvement by FDG-PET is a significant prognostic factor
      for overall survival. Local control at primary site remains of paramount
      importance for patient with nodal involvement. Isolated nodal failures are
      scarce.

PMID- 22387195
TI  - Expression pattern, subcellular localization, and functional implications of ODAM
      in ameloblasts, odontoblasts, osteoblasts, and various cancer cells.
AB  - During tooth development and tumorigenesis, the odontogenic ameloblast-associated
      protein (ODAM) is involved in cellular differentiation and matrix protein
      production. However, the precise function of ODAM remains largely unknown. To
      suggest new functional roles of ODAM, we investigated the cellular expression and
      subcellular localization of ODAM in tooth and cancer cells. ODAM was expressed in
      ameloblasts, odontoblasts, and osteoblasts in vivo and in vitro. Furthermore,
      ODAM was localized in both the nucleus and cytoplasm of MMP-20 expressing
      ameloblasts and odontoblasts, but only in the cytoplasm of non-MMP-20 expressing
      osteoblasts. The extracellular secretion of ODAM was not observed in odontoblasts
      and osteoblasts, but was seen in ameloblasts. In addition, ODAM was discovered in
      the nucleus, cytoplasm, and extracellular matrix of various cancer cells. These
      results suggest that the expression pattern and subcellular localization of ODAM
      is highly variable and dependent on cell types and their differentiation states,
      and that functional correlations exist between ODAM and MMP-20. This study
      provides the first evidence for ODAM in multiple cellular compartments of
      differentiating odontogenic and cancer cell lines with important functional
      implications. 

PMID- 22387197
TI  - Glutathione regulates caspase-dependent ceramide production and curcumin-induced
      apoptosis in human leukemic cells.
AB  - Depletion of intracellular glutathione (GSH) is the prime hallmark of the
      progression of apoptosis. Previously, we reported that curcumin induces reactive
      oxygen species (ROS)-mediated depletion of GSH, which leads to caspase-dependent
      and independent apoptosis in mouse fibroblast cells (F. Thayyullathil et al.,
      Free Radic. Biol. Med.45, 1403-1412, 2008). In this study, we investigated the
      antileukemic potential of curcumin in vitro, and we further examined the
      molecular mechanisms of curcumin-induced apoptosis in human leukemic cells.
      Curcumin suppresses the growth of human leukemic cells via ROS-independent GSH
      depletion, which leads to caspase activation, inhibition of sphingomyelin
      synthase (SMS) activity, and induction of ceramide (Cer) generation. Pretreatment
      of leukemic cells with carbobenzoxy-Val-Ala-Asp fluoromethylketone, a universal
      inhibitor of caspases, abrogates the SMS inhibition and Cer generation, and in
      turn prevents curcumin-induced cell death. Curcumin treatment of leukemic cells
      also downregulates the expression of the inhibitor of apoptosis proteins (IAPs),
      phospho-Akt, c-Myc, and cyclin D1. Extracellular supplementation with GSH
      attenuates curcumin-induced depletion of GSH, caspase-dependent inhibition of
      SMS, Cer generation, and downregulation of IAPs, whereas, L-D-buthionine
      sulfoximine, a widely used inhibitor of GSH synthesis, potentiates GSH depletion,
      Cer generation, and apoptosis induced by curcumin. Taken together, our findings
      provide evidence suggesting for the first time that GSH regulates caspase
      dependent inhibition of SMS activity, Cer generation, and apoptosis induced by
      curcumin in human leukemic cells.

PMID- 22387196
TI  - Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S
      nitrosylation.
AB  - The NADPH oxidases (Noxs) are a family of transmembrane oxidoreductases that
      produce superoxide and other reactive oxygen species (ROS). Nox5 was the last of
      the conventional Nox isoforms to be identified and is a calcium-dependent enzyme
      that does not depend on accessory subunits for activation. Recently, Nox5 was
      shown to be expressed in human blood vessels and therefore the goal of this study
      was to determine whether nitric oxide (NO) can modulate Nox5 activity.
      Endogenously produced NO potently inhibited basal and stimulated Nox5 activity
      and this inhibition was reversible with chronic, but not acute, exposure to L
      NAME. Nox5 activity was reduced by NO donors, iNOS, and eNOS and in endothelial
      cells and LPS-stimulated smooth muscle cells in a manner dependent on NO
      concentration. ROS production was diminished by NO in an isolated enzyme activity
      assay replete with surplus calcium and NADPH. There was no evidence for NO
      dependent changes in tyrosine nitration, glutathiolation, or phosphorylation of
      Nox5. In contrast, there was evidence for the increased nitrosylation of Nox5 as
      determined by the biotin-switch assay and mass spectrometry. Four S-nitrosylation
      sites were identified and of these, mutation of C694 dramatically lowered Nox5
      activity, NO sensitivity, and biotin labeling. Furthermore, coexpression of the
      denitrosylation enzymes thioredoxin 1 and GSNO reductase prevented NO-dependent
      inhibition of Nox5. The potency of NO against other Nox enzymes was in the order
      Nox1 >= Nox3 > Nox5 > Nox2, whereas Nox4 was refractory. Collectively, these
      results suggest that endogenously produced NO can directly S-nitrosylate and
      inhibit the activity of Nox5.

PMID- 22387198
TI  - Oxidative damage in human gingival fibroblasts exposed to cigarette smoke.
AB  - Cigarette smoke, a complex mixture of over 7000 chemicals, contains many
      components capable of eliciting oxidative stress, which may induce smoking
      related disorders, including oral cavity diseases. In this study, we investigated
      the effects of whole (mainstream) cigarette smoke on human gingival fibroblasts
      (HGFs). Cells were exposed to various puffs (0.5-12) of whole cigarette smoke and
      oxidative stress was assessed by 2',7'-dichlorofluorescein fluorescence. The
      extent of protein carbonylation was determined by use of 2,4
      dinitrophenylhydrazine with both immunocytochemical and Western immunoblotting
      assays. Cigarette smoke-induced protein carbonylation exhibited a puff-dependent
      increase. The main carbonylated proteins were identified by means of two
      dimensional electrophoresis and MALDI-TOF mass spectrometry (redox proteomics).
      We demonstrated that exposure of HGFs to cigarette smoke decreased cellular
      protein thiols and rapidly depleted intracellular glutathione (GSH), with a
      minimal increase in the intracellular levels of glutathione disulfide and S
      glutathionylated proteins, as well as total glutathione levels. Mass
      spectrometric analyses showed that total GSH consumption is due to the export by
      the cells of GSH-acrolein and GSH-crotonaldehyde adducts. GSH depletion could be
      a mechanism for cigarette smoke-induced cytotoxicity and could be correlated with
      the reduced reparative and regenerative activity of gingival and periodontal
      tissues previously reported in smokers.

PMID- 22387199
TI  - Genetic variation in antioxidant enzymes and lung function.
AB  - Not all cigarette smokers develop chronic obstructive pulmonary disease, and
      discovering susceptibility factors is an important research priority. The
      oxidative burden of smoking may overwhelm antioxidant defenses, and
      vulnerabilities may exist as a result of sequence variants in genes encoding
      antioxidant enzymes. This study explored the association between genetic
      variation in a network of antioxidant enzymes and lung phenotypes. Linear models
      evaluated single-locus marker associations in 2387 European American and African
      American participants in the Health, Aging, and Body Composition Study. After
      corrections were made for multiple comparisons, 15 statistically significant
      associations were identified, all of which were for SNP by smoking interactions.
      The most statistically significant findings were for genes encoding members of
      the isocitrate dehydrogenase gene family (IDH3A, IDH3B, IDH2). For rs6107100
      (IDH3B) the variant genotype was associated with a difference of 6% in the
      FEV(1)/FVC ratio in African American current smokers, but the SNP had little or
      no association with FEV(1)/FVC in former and never smokers (nominal
      p(interaction)=5*10(-6)). A variant of the peroxiredoxin gene (rs9787810, PRDX5)
      was associated with lower percentage predicted FEV(1) and a lower ratio in
      European American current smokers, with little or no association in other smoking
      groups (nominal p(interaction)=0.0001 and 0.0003, respectively). The studied
      genes have not been reported in previous candidate gene association studies, and
      thus the findings suggest novel mechanisms and targets for future research and
      provide evidence for a contribution of sequence variation in genes encoding
      antioxidant enzymes to susceptibility in smokers.

PMID- 22387200
TI  - The glutathionylation of p65 modulates NF-kappaB activity in 15-deoxy-Delta12,14
      prostaglandin J2-treated endothelial cells.
AB  - Protein glutathionylation is a posttranslational modification of cysteine
      residues with glutathione in response to mild oxidative stress. Because 15-deoxy
      Delta12,14-prostaglandin J(2) (15d-PGJ(2)) is an electrophilic prostaglandin that
      can increase glutathione (GSH) levels and augment reactive oxygen species (ROS)
      production, we hypothesized that it induces NF-kappaB-p65 glutathionylation and
      would exert anti-inflammatory effects. Herein, we show that 15d-PGJ(2) suppresses
      the expression of ICAM-1 and NF-kappaB-p65 nuclear translocation. 15d-PGJ(2)
      upregulates the Nrf2-related glutathione synthase gene and thereby increases the
      GSH levels. Consistent with this, Nrf2 siRNA molecules abolish the inhibition of
      p65 nuclear translocation in 15d-PGJ(2)-induced endothelial cells (ECs). ECs
      treated with GSSG show increased thiol modifications of p65 and also a block in
      TNFalpha-induced p65 nuclear translocation and ICAM-1 expression, but not in
      IkappaBalpha degradation. However, the overexpression of glutaredoxin 1 was found
      to be accompanied by a modest increase in NF-kappaB activity. Furthermore, we
      found that multiple cysteine residues in p65 are responsible for
      glutathionylation. 15d-PGJ(2) was observed to induce p65 glutathionylation and is
      suppressed by a GSH synthesis inhibitor, buthionine sulfoximine, by catalase, and
      by Nrf2 siRNA molecules. Our results thus indicate that the GSH/ROS-dependent
      glutathionylation of p65 is likely to be responsible for 15d-PGJ(2)-mediated NF
      kappaB inactivation and for the enhanced inhibitory effects of 15d-PGJ(2) on
      TNFalpha-treated ECs.

PMID- 22387201
TI  - [Schwannoma of the sciatic nerve: a rare cause of non-discal sciatica].

PMID- 22387202
TI  - [Vocal cord paralysis secondary to vincristine].

PMID- 22387203
TI  - [Neurologic paraneoplastic syndrome with anti-CV2/CRMP5 antibodies revealing a
      small cell lung cancer. Effectiveness of the lung cancer treatment].
AB  - INTRODUCTION: Paraneoplastic neurological syndrome associated with anti-CV2/CRMP5
      antibodies are rare. Various clinical manifestations can occur, cerebellar
      ataxia, polyneuropathy, optic neuritis with NORB or uveitis. Small cell lung
      carcinoma is generally responsible. CASE REPORT: We report the case of a 64-year
      old man who developed visual symptoms with papilledema, cerebellar signs,
      polyneuropathy confirmed with a neurophysiological studies. Anti-CV2/CRMP5
      antibodies were present. A small cell lung carcinoma was responsible for this
      paraneoplastic syndrome revealing the cancer. The paraneoplastic syndrome
      improved with radio chemotherapy of the cancer alone. CONCLUSION: A
      paraneoplastic neurological syndrome must be evoked in case of an atypic
      neurological syndrome. This diagnostic can be confirmed by the presence of anti
      neuronal antibodies. In this case, a small cells cancer of the lung must be
      research.

PMID- 22387204
TI  - Figures and institutions of the neurological sciences in Paris from 1800 to 1950.
      Part III: neurology.
AB  - We present a short historical review of the major figures, their administrative
      functions and their works that contributed to make Paris a renowned centre of
      physiology and neurology during the xixth and the first half of the xxth century.
      We purposely chose to focus on the period 1800-1950, as 1800 corresponds to the
      actual beginning of neurosciences, and 1950 marks their exponential rise. Our
      presentation is divided into four chapters, matching the main disciplines which
      have progressed and contributed the most to the knowledge we have of the brain
      sciences: anatomy, physiology, neurology, and psychiatry-psychology. The present
      article is the third of four parts of this review, and deals with neurology. A
      special credit should be given to Jean-Martin Charcot who founded the Salpetriere
      School of neurology and became one of the world's most important neurologists of
      the xixth century. We provide below the biographical sketches of Armand
      Trousseau, Guillaume Benjamin Amand Duchenne, Jean-Martin Charcot, Alfred
      Vulpian, Desire-Magloire Bourneville, Paul Richer, Henri Parinaud, Albert Pitres,
      Jules Joseph Dejerine, Mrs. Augusta Dejerine-Klumpke, Edouard Brissaud, Pierre
      Marie, Georges Edouard Brutus Gilles de la Tourette, Joseph Babinski, Andre
      Thomas, Georges Marinesco, Achille Alexandre Souques, Georges Guillain and
      Charles Foix.

PMID- 22387205
TI  - PP2A holoenzymes negatively and positively regulate cell cycle progression by
      dephosphorylating pocket proteins and multiple CDK substrates.
AB  - Cell cycle progression is negatively regulated by the retinoblastoma family of
      pocket proteins and CDK inhibitors (CKIs). In contrast, CDKs promote progression
      through multiple phases of the cell cycle. One prominent way by which CDKs
      promote cell cycle progression is by inactivation of pocket proteins via
      hyperphosphorylation. Reactivation of pocket proteins to halt cell cycle
      progression requires dephosphorylation of multiple CDK-phosphorylated sites and
      is accomplished by PP2A and PP1 serine/threonine protein phosphatases. The same
      phosphatases are also implicated in dephosphorylation of multiple CDK substrates
      as cells exit mitosis and reenter the G1 phase of the cell cycle. This review is
      primarily focused on the role of PP2A and PP1 in the activation of pocket
      proteins during the cell cycle and in response to signaling cues that trigger
      cell cycle exit. Other functions of PP2A during the cell cycle will be discussed
      in brief, as comprehensive reviews on this topic have been published recently (De
      Wulf et al., 2009; Wurzenberger and Gerlich, 2011).

PMID- 22387206
TI  - A case of del(13)(q14.2)(q31.3) associated with hypothyroidism,
      hypertriglyceridemia, hypercholesterolemia and total ophthalmoplegia.
AB  - 13q deletion syndrome is caused by the absence of a portion of the long arm of
      chromosome 13. This syndrome is a rare condition characterized by a wide range of
      clinical findings. Phenotype varies with the location and size of the deletion.
      We report a female dizygotic twin with a proximal deletion of 13q and failure to
      thrive, hypotonia, and multiple anomalies included pytosis and total
      ophthalmology at right side, strabismus at left, bilateral iris heterochromia and
      telecantus. She had a broad nasal bridge with flat philtrum, micrognathia and
      antevert ear lobes. Her umbilicus had vanished. Her left coxa was dislocated and
      left toes were overlapped. She was also found to have hypertriglyceridemia,
      hypercholesterolemia, and hypothyroidism. Chromosome analysis showed a proximal
      deletion of chromosome 13 [karyotype 46,XX,del(13) (q14.2q31.3)] which was
      confirmed by high-resolution microarray based comparative genomic hybridization.
      The described patient is unique among similar rare cases with different deletion
      breakpoints. It is the first case of 13q14.2q31.3 deletion where the breakpoints
      are clearly defined, indicating the importance of detailed clinical description
      and high-resolution genomic analysis for characterization of rare genetic
      syndromes.

PMID- 22387207
TI  - Cloning, localization and differential expression of the Trypanosoma cruzi TcOGNT
      2 glycosyl transferase.
AB  - The surface of Trypanosoma cruzi is covered by a dense glycocalix which is
      characteristic of each stage of the life cycle. Its composition and complexity
      depend mainly on mucin-like proteins. A remarkable feature of O-glycan
      biosynthesis in trypanosomes is that it initiates with the addition of a GlcNAc
      instead of the GalNAc residue that is commonly used in vertebrate mucins. The
      fact that the interplay between trans-sialidase and mucin is crucial for
      pathogenesis, and both families have stage-specific members is also remarkable.
      Recently the enzyme that transfers the first GlcNAc from UDP-GlcNAc to a serine
      or threonine residue was kinetically characterized. The relevance of this enzyme
      is evidenced by its role as catalyzer of the first step in O-glycosylation. In
      this paper we describe how this gene is expressed differentially along the life
      cycle with a pattern that is very similar to that of trans-sialidases. Its
      localization was determined, showing that the protein predicted to be in the
      Golgi apparatus is also present in reservosomes. Finally our results indicate
      that this enzyme, when overexpressed, enhances T. cruzi infectivity.

PMID- 22387208
TI  - NBP, a zebrafish homolog of human Kank3, is a novel Numb interactor essential for
      epidermal integrity and neurulation.
AB  - Numb is an adaptor protein implicated in diverse basic cellular processes. Using
      the yeast-two hybrid system we isolated a novel Numb interactor in zebrafish
      called NBP which is an ortholog of human renal tumor suppressor Kank. NBP
      interacts with the PTB domain of Numb through a region well conserved among
      vertebrate Kanks containing the NGGY sequence. Similar NBP and Numb morphant
      phenotype such as impaired convergence and extension movements during
      gastrulation, neurulation and epidermis defects and enhanced phenotypic
      aberrations in double morphants suggest that the genes interact genetically. We
      demonstrate that the expression of NBP undergoes quantitative and qualitative
      changes during embryogenesis and that the protein accumulates at the cell
      periphery to sites of cell-cell contact during gastrulation and later in
      development it concentrates at the basal poles of differentiated cells. These
      findings imply a possible role of NBP in establishing and maintaining cell
      adhesion and tissue integrity.

PMID- 22387209
TI  - Retinoic acid signaling and the initiation of mammary gland development.
AB  - Retinoic acid receptors (RARs), which are involved in retinoic acid signal
      transduction, are essential for maintaining the differentiated state of
      epithelial tissues. Mammary glands are skin appendages whose development is
      initiated through continuous cell-cell interactions between the ectoderm and the
      adjacent mesenchyme. Considerable progress has been made in elucidating the
      molecular basis of these interactions in mammary gland formation in mouse
      embryos, including the network of initiating signals comprising Fgfs, Wnts and
      Bmps involved in gland positioning and the transcription factors, Tbx3 and Lef1,
      essential for mammary gland development. Here, we provide evidence that retinoic
      acid signaling may also be involved in mammary gland development. We documented
      the expression of gene-encoding enzymes that produce retinoic acid (Raldh2) and
      enzymes that degrade it (Cyp26a1, Cyp26b1). We also analyzed the expression of
      RAR-beta, a direct transcriptional target of retinoic acid signaling. Raldh2 and
      RAR-beta were expressed in E10-E10.5 mouse embryos in somites adjacent to the
      flank region where mammary buds 2, 3 and 4 develop. These expression patterns
      overlapped with that of Fgf10, which is known to be required for mammary gland
      formation. RAR-beta was also expressed in the mammary mesenchyme in E12 mouse
      embryos; RAR-beta protein was expressed in the mammary epithelium and developing
      fat pad. Retinoic acid levels in organ cultures of E10.5 mouse embryo flanks were
      manipulated by adding either retinoic acid or citral, a retinoic acid synthesis
      inhibitor. Reduced retinoic acid synthesis altered the expression of genes
      involved in retinoic acid homeostasis and also demonstrated that retinoic acid
      signaling is required for Tbx3 expression, whereas high levels of retinoic acid
      signaling inhibited Bmp4 expression and repressed Wnt signaling. The results of
      the experiments using RNAi against Tbx3 and Wnt10b suggested feedback
      interactions that regulate retinoic acid homeostasis in mammary gland-forming
      regions. We produced a molecular model for mammary gland initiation that
      incorporated retinoic acid signaling.

PMID- 22387210
TI  - Growth inhibition and apoptosis by an active component of OK-432, a streptococcal
      agent, via Toll-like receptor 4 in human head and neck cancer cell lines.
AB  - Toll-like receptor 4 (TLR4) plays a significant role in cancer therapy as
      receptors of bacteria-derived immunotherapeutic agents such as OK-432, a
      streptococcal immunotherapeutic agent. In addition, recent reports demonstrated
      that TLRs, including TLR4, are also expressed in cancer cells as well as in
      immunocompetent cells. It is a problem in cancer therapy that the immunoadjuvant
      may activate survival signals such as nuclear factor (NF)-kappaB or mitogen
      activated protein kinases (MAPKs) in cancer cells via TLRs. In the current study,
      we investigated responsiveness of human head and neck cancer cell lines against
      TLR4 ligands, OK-PSA, an active component of OK-432, and a lipopolysaccharide
      (LPS). Stimulation with LPS or OK-PSA resulted in the activation of NF-kappaB in
      these cell lines expressing TLR4 and MD-2 that is a significant coreceptor for
      TLR4 signaling. Interestingly, OK-PSA induced cell-growth inhibition, while LPS
      enhanced the proliferation of the cancer cells. OK-PSA induced NF-kappaB
      activation more slowly than that induced by LPS. In addition, phosphorylation of
      p38 MAPK by OK-PSA was only slight compared with that by LPS. OK-PSA also induced
      apoptosis of the cancer cells mediated by the activation of caspase 1, 3 and 8 in
      a p53-independent manner. These findings strongly suggest that active components
      of OK-432 may elicit anti-cancer effects via enhancing host immunity as well as
      via directly inducing the growth inhibition and apoptosis of head and neck cancer
      cells through TLR4 signal.

PMID- 22387211
TI  - ALG11--a new variable DNA marker for sponge phylogeny: comparison of phylogenetic
      performances with the 18S rDNA and the COI gene.
AB  - Phylogenetic relationships within sponge classes are highly debated. The low
      phylogenetic signal observed with some current molecular data can be attributed
      to the use of few markers, usually slowly-evolving, such as the nuclear rDNA
      genes and the mitochondrial COI gene. In this study, we conducted a
      bioinformatics search for a new molecular marker. We sought a marker that (1) is
      likely to have no paralogs; (2) evolves under a fast evolutionary rate; (3) is
      part of a continuous exonic region; and (4) is flanked by conserved regions. Our
      search suggested the nuclear ALG11 as a potential suitable marker. We next
      demonstrated that this marker can indeed be used for solving phylogenetic
      relationships within sponges. Specifically, we successfully amplified the ALG11
      gene from DNA samples of representatives from all four sponge classes as well as
      from several cnidarian classes. We also amplified the 18S rDNA and the COI gene
      for these species. Finally, we analyzed the phylogenetic performance of ALG11 to
      solve sponge relationships compared to and in combination with the nuclear 18S
      rDNA and the COI mtDNA genes. Interestingly, the ALG11 marker seems to be
      superior to the widely-used COI marker. Our work thus indicates that the ALG11
      marker is a relevant marker which can complement and corroborate the phylogenetic
      inferences observed with nuclear ribosomal genes. This marker is also expected to
      contribute to resolving evolutionary relationships of other apparently slow
      evolving animal phyla, such as cnidarians.

PMID- 22387212
TI  - Neurosurgery in Siberia.
AB  - There is archaeological evidence that the first neurosurgical procedure in what
      is now known as Siberia was performed in 8005 +/- 100 B.C. According to signs of
      bone growth, perhaps more than half of the individuals who received the ancient
      trepanations survived. In Siberia, the first operations on the human brain and
      spinal cord were performed in 1909 at Tomsk University Hospital by the
      outstanding Russian surgeon and professor Vladimir M. Mysh. Professor Mysh
      initially moved from Saint Petersburg to Tomsk and later to Novosibirsk. Nicolay
      N. Burdenko, the founder of Russian neurosurgery and the Moscow Neurosurgical
      Institution, began his medical education at the Tomsk Imperial University. In the
      1950s, Professor Ksenia I. Kharitonova exerted her great influence upon the
      development of neurosurgery in Siberia. Since 1955, and for 30 years thereafter,
      Professor Kharitonova was recognized as a principal leader of Siberian
      neurosurgery. She applied every effort to spread neurosurgical knowledge, and she
      popularized best practices around Siberia and the Far East. Perestroika
      deconstructed and ultimately eliminated the orderly system of neurosurgical
      service in the Soviet Union. From another perspective, the process opened the
      window to the world. Fully equipped centers and clinics with state-of-the-art
      techniques for neuro-oncology, cerebrovascular diseases, neurotrauma, and spinal
      pathology management in Novosibirsk, Barnaul, Kemerovo, and Irkutsk were enabled.

PMID- 22387214
TI  - Architectural organization in E. coli nucleoid.
AB  - In contrast to organized hierarchical structure of eukaryotic chromosome,
      bacterial chromosomes are believed not to have such structures. The genomes of
      bacteria are condensed into a compact structure called the nucleoid. Among many
      architectural, histone-like proteins which associate with the chromosomal DNA is
      HU which is implicated in folding DNA into a compact structure by bending and
      wrapping DNA. Unlike the majority of other histone-like proteins, HU is highly
      conserved in eubacteria and unique in its ability to bind RNA. Furthermore, an HU
      mutation profoundly alters the cellular transcription profile and consequently
      has global effects on physiology and the lifestyle of E. coli. Here we provide a
      short overview of the mechanisms by which the nucleoid is organized into
      different topological domains. We propose that HU is a major player in creating
      domain-specific superhelicities and thus influences the transcription profile
      from the constituent promoters. This article is part of a Special Issue entitled:
      Chromatin in time and space.

PMID- 22387215
TI  - E2A proteins enhance the histone acetyltransferase activity of the
      transcriptional co-activators CBP and p300.
AB  - The E2A gene encodes the E-protein transcription factors E12 and E47 that play
      critical roles in B-lymphopoiesis. A somatic chromosomal translocation detectable
      in 5% of cases of acute lymphoblastic leukemia (ALL) involves E2A and results in
      expression of the oncogenic transcription factor E2A-PBX1. CREB binding protein
      (CBP) and its close paralog p300 are transcriptional co-activators with intrinsic
      histone acetyltransferase (HAT) activity. We and others have shown that direct
      binding of an N-terminal transcriptional activation domain present in E12/E47 and
      E2A-PBX1 to the KIX domain of CBP/p300 contributes to E2A protein function. In
      the current work we show for the first time that the catalytic HAT activity of
      CBP/p300 is increased in the presence of residues 1-483 of E2A (i.e., the portion
      present in E2A-PBX1). The addition of purified, recombinant E2A protein to in
      vitro assays results in a two-fold augmentation of CBP/p300 HAT activity, whereas
      in vivo assays show a ten-fold augmentation of HAT-dependent transcriptional
      induction and a five-fold augmentation of acetylation of reporter plasmid
      associated histone by CBP in response to co-transfected E2A. Our results indicate
      that the HAT-enhancing effect is independent of the well-documented E2A-CBP
      interaction involving the KIX domain and suggest a role for direct, perhaps low
      affinity binding of E2A to a portion of CBP that includes the HAT domain and
      flanking elements. Our findings add to a growing body of literature indicating
      that interactions between CBP/p300 and transcription factors can function in a
      specific manner to modulate HAT catalytic activity.

PMID- 22387213
TI  - To the pore and through the pore: a story of mRNA export kinetics.
AB  - The evolutionary 'decision' to store genetic information away from the place of
      protein synthesis, in a separate compartment, has forced eukaryotic cells to
      establish a system to transport mRNAs from the nucleus to the cytoplasm for
      translation. To ensure export to be fast and efficient, cells have evolved a
      complex molecular interplay that is tightly regulated. Over the last few decades,
      many of the individual players in this process have been described, starting with
      the composition of the nuclear pore complex to proteins that modulate co
      transcriptional events required to prepare an mRNP for export to the cytoplasm.
      How the interplay between all the factors and processes results in the efficient
      and selective export of mRNAs from the nucleus and how the export process itself
      is executed within cells, however, is still not fully understood. Recent advances
      in using proteomic and single molecule microscopy approaches have provided
      important insights into the process and its kinetics. This review summarizes
      these recent advances and how they led to the current view on how cells
      orchestrate the export of mRNAs. This article is part of a Special Issue
      entitled: Nuclear Transport and RNA Processing.

PMID- 22387216
TI  - Behaviour of HPMC compacts investigated using UV-imaging.
AB  - The aim of the study was to visualize the behaviour of the hydroxypropyl
      methylcellulose (HPMC) in a buffer solution using UV imaging. The obtained
      results were related to rheological measurements in order to gain insight into
      critical polymer properties affecting drug release. Two viscosity grades of HPMC,
      15cP and 50 cP, were used. The behaviour of the polymer at the surface of the
      compact was observed by UV-imaging at 214 nm for 90 min in a stagnant buffer
      solution and in presence of flow. Steady shear and oscillatory shear measurements
      were conducted to determine the rheological characteristics. Three distinctive
      phases could be detected by real-time UV-imaging of the HPMC; gel formation due
      to water penetration, further expansion of the gel into solution and finally
      steady conditions, where a critical polymer concentration that can withstand the
      shear forces without eroding was observed. The critical concentration
      corresponded to the rheologically determined gel point, which is the lowest
      concentration where a 3D-network is obtained. Higher viscosity grade HPMC swelled
      more rapidly and lead to a thicker gel layer, which was more resistant towards
      the shear forces due to the applied flow. The results showed that UV imaging is
      suitable for obtaining both qualitative and quantitative information on polymer
      behaviour.

PMID- 22387217
TI  - Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells
      involving inhibition of Stat5 signaling.
AB  - Indirubin is the major active anti-tumor component of a traditional Chinese
      herbal medicine used for treatment of chronic myelogenous leukemia (CML). While
      previous studies indicate that indirubin is a promising therapeutic agent for
      CML, the molecular mechanism of action of indirubin is not fully understood. We
      report here that indirubin derivatives (IRDs) potently inhibit Signal Transducer
      and Activator of Transcription 5 (Stat5) protein in CML cells. Compound E804,
      which is the most potent in this series of IRDs, blocked Stat5 signaling in human
      K562 CML cells, imatinib-resistant human KCL-22 CML cells expressing the T315I
      mutant Bcr-Abl (KCL-22M), and CD34-positive primary CML cells from patients.
      Autophosphorylation of Src family kinases (SFKs) was strongly inhibited in K562
      and KCL-22M cells at 5 MUM E804, and in primary CML cells at 10 MUM E804,
      although higher concentrations partially inhibited autophosphorylation of Bcr
      Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate
      downstream Stat5 signaling. Activation of Stat5 was strongly blocked by E804 in
      CML cells. E804 down-regulated expression of Stat5 target proteins Bcl-x(L) and
      Mcl-1, associated with induction of apoptosis. In sum, our findings identify IRDs
      as potent inhibitors of the SFK/Stat5 signaling pathway downstream of Bcr-Abl,
      leading to apoptosis of K562, KCL-22M and primary CML cells. IRDs represent a
      promising structural class for development of new therapeutics for wild type or
      T315I mutant Bcr-Abl-positive CML patients.

PMID- 22387219
TI  - Influenza virus inactivated by artificial ribonucleases as a prospective killed
      virus vaccine.
AB  - The inactivation of viral particles with agents causing minimal damage to the
      structure of surface epitopes is a well-established approach for the production
      of killed virus vaccines. Here, we describe new agents for the inactivation of
      influenza virus, artificial ribonucleases (aRNases), which are chemical compounds
      capable of cleaving RNA molecules. Several aRNases were identified, exhibiting
      significant virucidal activity against the influenza A virus and causing a
      minimal effect on the affinity of monoclonal antibodies for the inactivated
      virus. Using a murine model of the influenza virus infection, a high protective
      activity of the aRNase-inactivated virus as a vaccine was demonstrated. The
      results of the experiments demonstrate the efficacy of novel chemical agents in
      the preparation of vaccines against influenza and, perhaps, against other
      infections caused by RNA viruses.

PMID- 22387218
TI  - Immunogenicity of a lentiviral-based DNA vaccine driven by the 5'LTR of the
      naturally attenuated caprine arthritis encephalitis virus (CAEV) in mice and
      macaques.
AB  - Increasing the safety and the efficacy of existing HIV vaccines is one of the
      strategies that could help to promote the development of a vaccine for human use.
      We developed a HIV DNA vaccine (Delta4-SHIVKU2) that has been shown to induce
      potent polyfunctional HIV-specific T cell responses following a single dose
      immunization of mice and macaques. Delta4-SHIVKU2 also induced protection when
      immunized macaques were challenged with homologous pathogenic viruses. In the
      present study, our aim was to examine whether a chimeric HIV DNA vaccine (CAL
      Delta4-SHIVKU2) whose genome is driven by the LTR of the goat lentivirus, caprine
      arthritis encephalitis (CAEV) expresses efficiently the vaccine antigens and
      induces potent immune responses in animal models for HIV vaccine. Data of
      radioimmunoprecipitation assays clearly show that this chimeric genome drives
      efficient expression of all HIV antigens in the construct. In addition,
      evaluation of the p24 Gag protein in the supernatant of HEK-293-T cells
      transfected in parallel with Delta4-SHIVKU2 and CAL-Delta4-SHIVKU2 showed no
      difference suggesting that these two LTRs are inducing equally the expression of
      the viral genes. Immunization of mice and macaques using our single dose
      immunization regimen resulted in induction of similar IFN-gamma ELISPOT responses
      in Delta4-SHIVKU2- and CAL-Delta4-SHIVKU2-treated mice. Similar profiles of T
      cell responses were also detected both in mice and macaques when multiparametric
      flow cytometry analyses were performed. Since CAEV LTR is not dependent of Tat to
      drive viral gene expression and is not functional for integration with HIV
      integrase, this new vector increases the safety and efficacy of our vaccine
      vectors and vaccination strategy.

PMID- 22387220
TI  - Economic analysis for evidence-based policy-making on a national immunization
      program: a case of rotavirus vaccine in Thailand.
AB  - Severe diarrhea caused by rotavirus is a health problem worldwide, including
      Thailand. The World Health Organization has recommended incorporating rotavirus
      vaccination into national immunization programs. This policy has been implemented
      in several countries, but not in Thailand where the mortality rate is not high.
      This leads to the question of whether it would be cost-effective to implement
      such a policy. The Thai National Vaccine Committee, through the Immunization
      Practice Subcommittee, has conducted an economic analysis. Their study aimed to
      estimate the costs of rotavirus diarrhea and of a rotavirus vaccination program,
      and the cost-effectiveness of such a program including budget impact analysis.
      The study was designed as an economic evaluation, employing modeling technique in
      both provider and societal perspectives. A birth cohort of Thai children in 2009
      was used in the analysis, with a 5-year time horizon. Costs were composed of cost
      of the illness and the vaccination program. Outcomes were measured in the form of
      lives saved and DALYs averted. Both costs and outcomes were discounted at 3%. The
      study found the discounted number of deaths to be 7.02 and 20.52 for vaccinated
      and unvaccinated cohorts, respectively (13.5 deaths averted). Discounted DALYs
      were 263.33 and 826.57 for vaccinated and unvaccinated cohorts, respectively
      (563.24 DALYs averted). Costs of rotavirus diarrhea in a societal perspective
      were US$6.6 million and US$21.0 million for vaccinated and unvaccinated cohorts,
      respectively. At base case, the costs per additional death averted were US$5.1
      million and US$5.7 for 2-dose and 3-dose vaccines, respectively, in a societal
      perspective. Costs per additional DALYs averted were US$128,063 and US$142,144,
      respectively. In a societal perspective, with a cost-effectiveness threshold at 1
      GDP per capita per DALYs averted, vaccine prices per dose were US$4.98 and
      US$3.32 for 2-dose and 3-dose vaccines, respectively; in a provider perspective,
      they were US$2.90 and US$1.93. One-way and probabilistic sensitivity analyses
      were included. The budget required for vaccine purchase was calculated for all
      scenarios.

PMID- 22387221
TI  - Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal
      trivalent influenza vaccines and A(H1N1)pdm09 vaccines: systematic review and
      meta-analyses.
AB  - Cross-protection by seasonal trivalent influenza vaccines (TIVs) against pandemic
      influenza A H1N1 2009 (now known as A[H1N1]pdm09) infection is controversial; and
      the vaccine effectiveness (VE) of A(H1N1)pdm09 vaccines has important health
      policy implications. Systematic reviews and meta-analyses are needed to assess
      the impacts of both seasonal TIVs and A(H1N1)pdm09 vaccines against
      A(H1N1)pdm09.We did a systematic literature search to identify observational
      and/or interventional studies reporting cross-protection of TIV and A(H1N1)pdm09
      VE from when the pandemic started (2009) until July 2011. The studies fulfilling
      inclusion criteria were meta-analysed. For cross-protection and VE, respectively,
      we stratified by vaccine type, study design and endpoint. Seventeen studies
      (104,781 subjects) and 10 studies (2,906,860 subjects), respectively, reported
      cross-protection of seasonal TIV and VE of A(H1N1)pdm09 vaccines; six studies
      (17,229 subjects) reported on both. Thirteen studies (95,903 subjects) of cross
      protection, eight studies (859,461 subjects) of VE, and five studies (9,643
      subjects) of both were meta-analysed and revealed: (1) cross-protection for
      confirmed illness was 19% (95% confident interval=13-42%) based on 13 case
      control studies with notable heterogeneity. A higher cross-protection of 34% (9
      52%) was found in sensitivity analysis (excluding five studies with moderate/high
      risk of bias). Further exclusion of studies that recruited early in the pandemic
      (when non-recipients of TIV were more likely to have had non-pandemic influenza
      infection that may have been cross-protective) dramatically reduced
      heterogeneity. One RCT reported cross-protection of 38% (19-53%) for confirmed
      illness. One case-control study reported cross-protection of 50% (40-59%) against
      hospitalisation. (2) VE of A(H1N1)pdm09 for confirmed illness was 86% (73-93%)
      based on 11 case-control studies and 79% (22-94%) based on two cohort studies; VE
      against medically-attended ILI was 32% (8-50%) in one cohort study. TIVs provided
      moderate cross-protection against both laboratory-confirmed A(H1N1)pdm09 illness
      (based on eight case-control studies with low risk of bias and one RCT) and also
      hospitalisation. A finding of increased risk from seasonal vaccine was limited to
      cases recruited early in the pandemic. A(H1N1)pdm09 vaccines were highly
      effective against confirmed A(H1N1)pdm09 illness. Although cross-protection was
      less than the direct effect of strain-specific vaccination against A(H1N1)pdm09,
      TIV was generally beneficial before A(H1N1)pdm09 vaccine was available.

PMID- 22387222
TI  - Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen
      specific cytotoxic T cell responses.
AB  - The complement system and Toll-like receptors (TLR) are key innate defense
      systems which might interact synergistically on dendritic cells (DC) to reinforce
      adaptive immunity. In a previous work, we found that the extra domain A from
      fibronectin EDA (an endogenous ligand for TLR4) can favour antigen delivery to DC
      and induce their maturation. Given the potential of anaphylatoxins to cause
      inflammation and activation of myeloid cells, we hypothesized that a fusion
      protein between EDA, and anaphylatoxins C3a, C4a or C5a together with an antigen
      might improve the immunogenicity of the antigen. Naked DNA immunization with a
      construct expressing the fusion protein between C5a, EDA and the cytotoxic T cell
      epitope SIINFEKL from ovalbumin, induced strong antigen specific T cell
      responses. The purified recombinant fusion protein EDA-SIINFEKL-C5a induced
      activation of dendritic cells, the production of proinflammatory
      cytokines/chemokines and stimulated antigen presenting cell migration and NK cell
      activation. As compared to EDA-SIINFEKL, the fusion protein EDA-SIINFEKL-C5a did
      not induce the production of the immunosuppressive molecules IL-10, CCL17, CCL1,
      CXCL12 or XCL1 by DC. Moreover, EDA-SIINFEKL-C5a induced strong specific T cell
      responses in vivo and protected mice against E.G7-OVA tumor growth more
      efficiently than EDA-SIINFEKL or SIINFEKL-C5a recombinant proteins. Our results
      suggest that fusion proteins containing EDA, the anaphylatoxin C5a and the
      antigen may serve as a suitable strategy for the development of anti-tumor or
      anti-viral vaccines.

PMID- 22387223
TI  - An alternate delivery system improves vaccine performance against foot-and-mouth
      disease virus (FMDV).
AB  - Foot-and-mouth disease virus (FMDV) causes vesicular disease of cloven-hoofed
      animals with severe agricultural and economic implications. One of the most
      highly infectious and contagious livestock pathogens known, the disease spreads
      rapidly in naive populations making it critical to have rapidly acting vaccines.
      Needle inoculation of killed virus vaccine is an efficient method of swiftly
      vaccinating large numbers of animals, either in eradication efforts or in
      outbreak situations in disease free countries, although, to be efficient, this
      requires utilizing the same needle with multiple animals. Here we present studies
      using a needle free system for vaccination with killed virus vaccine, FMDV strain
      O1 Manisa, as a rapid and consistent delivery platform. Cattle were vaccinated
      using a commercially available vaccine formulation at the manufacturer's
      recommended dose as well as four and sixteen fold less antigen load per dose.
      Animals were challenged intradermalingually (IDL) with live, virulent virus,
      homologous strain O1 Manisa, at various times following vaccination. All non
      vaccinated control cattle exhibited clinical disease, including fever, viremia
      and lesions, specifically vesicle formation. Cattle vaccinated with the 1/16* and
      1/4* doses using the needle free device were protected when challenged at both 7
      and 28 days after vaccination. These data suggest that effective protection
      against disease can be achieved with 1/16 of the recommended vaccine dose when
      delivered using the needle free, intradermal delivery system, indicating the
      current vaccine stockpile that can be extended by many fold using this system.

PMID- 22387224
TI  - Fyn positively regulates the activation of DAP12 and FcRgamma-mediated
      costimulatory signals by RANKL during osteoclastogenesis.
AB  - Osteoclasts (OCs) are the only bone-resorbing cells and are critically involved
      in various bone-associated diseases, including osteoporosis and rheumatoid
      arthritis. Differentiation of OCs from bone marrow macrophage cells (BMMs) is
      regulated by RANK and the adaptor protein (DAP12/FcRgamma)-mediated costimulatory
      signals. However, it is unknown how RANKL/RANK signal stimulates phosphorylation
      of DAP12/FcRgamma to initiate the costimulatory signals. As reported here, we
      found that OC differentiation and acquisition of bone resorption capacity were
      suppressed in RANKL-stimulated Fyn(-/-) or Fyn-siRNA-transfected BMMs, but could
      be restored by overexpression of Fyn kinase in Fyn(-/-) BMMs. However, the RANKL
      stimulated proliferation of BMMs was unaffected by the absence of Fyn. In
      addition, RANKL-stimulated Fyn(-/-) BMMs no longer exhibited the optimal
      induction of typical OC markers such as NFATc1, c-Fos, c-Src, TRAF6, and
      cathepsin K or costimulatory signals such as the activating phosphorylations of
      Syk, PLCgamma2, and Gab2. These were restored by overexpression of Fyn in Fyn(-/
      ) BMMs. Immunoprecipitation studies also indicated that the adaptor proteins
      DAP12/FcRgamma and Syk interacted with RANK during RANKL stimulation in BMMs in a
      Fyn-dependent manner. Phosphorylation of the DAP12/FcRgamma and the recruitment
      of Syk by DAP12/FcRgamma were suppressed in Fyn(-/-) BMMs. This is the first
      demonstration that Fyn relays the initial RANK/RANKL signal to the ITAM
      containing adaptors DAP12/FcRgamma for OC differentiation.

PMID- 22387225
TI  - STIM1 tyrosine-phosphorylation is required for STIM1-Orai1 association in human
      platelets.
AB  - Stromal interaction molecule 1 (STIM1) is a key element of the store-operated
      Ca(2+) entry mechanism (SOCE). Recently, regulation of STIM1 by glycosylation and
      phosphorylation on serine/threonine or proline residues has been described;
      however other modes of phosphorylation that are important for activating SOCE in
      platelets, such as tyrosine phosphorylation, have been poorly investigated. Here
      we investigate the latency of STIM1 phosphorylation on tyrosine residues during
      the first steps of SOCE activation. Human platelets were stimulated and fixed at
      desired times using rapid kinetic assays instruments, and immunoprecipitation and
      western blotting techniques were then used to investigate the pattern of STIM1
      tyrosine phosphorylation during the first steps of SOCE activation. We have found
      that maximal STIM1 tyrosine phosphorylation occurred 2.5s after stimulation of
      human platelets with thapsigargin (Tg). STIM1 localized in the plasma membrane
      were also phosphorylated in platelets stimulated with Tg. By using chemical
      inhibitors that target different members of the Src family of tyrosine kinases
      (SKFs), two independent signaling pathways involved in STIM1 tyrosine
      phosphorylation during the first steps of SOCE activation were identified. We
      finally conclude that STIM1 tyrosine phosphorylation is a key event for the
      association of STIM1 with plasma membrane Ca(2+) channels such as Orai1, hence it
      is required for conducting SOCE activation.

PMID- 22387226
TI  - Ecklonia cava polyphenol protects the liver against ethanol-induced injury in
      rats.
AB  - BACKGROUND: The development of alcoholic liver disease is a complex process that
      involves both the parenchymal and non-parenchymal cells of the liver. We examined
      the effect of an Ecklonia cava extract on ethanol-induced liver injury. METHODS:
      Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with
      ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been
      incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or
      0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking
      water containing 5% ethanol and were also treated with carbon tetrachloride
      (CCl4) (0.1 ml/kg of body weight). RESULTS: In the cultured hepatocytes, the ECP
      treatment suppressed the ethanol-induced increase in cell death by maintaining
      intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the
      ethanol-induced increases in type I collagen and alpha-smooth muscle actin
      expression by maintaining intracellular levels of reactive oxygen species and
      GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the
      progression of liver fibrosis in rats treated with ethanol and CCl4. ECP
      treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4
      treated rats. ECP treatment fully protected the rats against ethanol- and CCl4
      induced liver injury. GENERAL SIGNIFICANCE: ECP may be a candidate for preventing
      ethanol-induced liver injury.

PMID- 22387227
TI  - Short-term effects of air pollution on respiratory morbidity at Rio de Janeiro-
      PART I: Air pollution assessment.
AB  - Exposure to air pollution has been related with the most varied adverse health
      outcomes. This study aims to assess the impact of air pollution on the emergency
      hospitalization for respiratory disease in Rio de Janeiro, Brazil. The study was
      divided in two parts: Part I specifically addressing the air pollution assessment
      and Part II addressing the health assessment. Accordingly, this Part I aims to:
      i) evaluate the concentrations of PM(10), SO(2) and CO at two sites in Rio de
      Janeiro and compare them; ii) analyse the concentrations observed according to
      the national and international standards; and iii) analyse the air pollutants
      behaviour, namely, annually, seasonally, daily and considering weekdays/weekends
      variations. The pollutant concentrations were measured at two different sites in
      Rio de Janeiro and the analysis was performed for the period between September
      2000 and December 2005. Results showed that PM(10) concentrations in Rio de
      Janeiro exceeded the daily and annual standards imposed by the European Union,
      the Brazilian legislation and WHO guidelines. Regarding SO(2) and CO,
      concentrations were, generally, below both European and Brazilian standards.
      Nevertheless, considering WHO guidelines, SO(2) threshold for daily
      concentrations (20 MUg m(-3)) was exceeded around 150 times. Behaviour assessment
      showed that the influence of traffic is a major factor affecting the air
      pollution in Rio de Janeiro. Considering the results achieved and the proven
      health effects of air pollution, strategies should be defined for its reduction,
      particularly concerning particulate matter, and consequently contribute to the
      protection of public health.

PMID- 22387229
TI  - Delay for the capacity-simplicity dilemma in associative memory attractor
      networks.
AB  - We consider the issue of how a simple network with delayed feedback can exhibit
      complex but desired dynamical behaviors for memory storage and retrieval. We
      discuss the simplicity-capacity dilemma arising from the requirement of both
      large capacity and easy implementation in additive networks. We then propose a
      novel approach based on signal processing delay and show that the interaction of
      delay, feedback and refractoriness in a simple inhibitory network of three
      neurons can generate mathematically trackable coexisting periodic patterns.
      Therefore, a simple and small network with delayed feedback can process a large
      amount of information, and time lag in our biological or artificial neural nets
      is useful for information processing. How the connection topology of a large
      network enhances the network's capacity for memory storage and retrieval remains
      to be an interesting task.

PMID- 22387228
TI  - Effects of 1alpha,25-dihydroxyvitamin D3 on transport and metabolism of adefovir
      dipivoxil and its metabolites in Caco-2 cells.
AB  - Effects of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), natural ligand of the
      VDR, on the fates of adefovir dipivoxil (P-gp substrate) and its metabolites,
      mono(POM)-PMEA and adefovir (MRP4 substrate), were investigated in Caco-2 cells.
      After 1,25(OH)2D3-treatment, higher apical efflux of adefovir was observed after
      a 60 min incubation of adefovir divipoxil. Changes in these washout studies were
      predicted by a catenary model for the Caco-2 monolayer that described a higher
      MRP4 activity with 1,25(OH)2D3 treatment, as confirmed by Western blotting.
      Moreover, 1,25(OH)2D3 treatment (100 nM for 3 days) resulted in increased
      basolateral (B) to apical (A) (B-to-A) transport of adefovir dipivoxil but an
      unchanged A-to-B flux, rendering an elevated efflux ratio (EfR) (from 1.97 to
      3.19). The EfR values in control and 1,25(OH)2D3-treated groups in these
      transport studies were reduced to 1.32 and 1.57, respectively, in the presence of
      verapamil (50 MUM), the P-gp inhibitor. The B-to-A transport of the metabolite,
      adefovir, was increased in 1,25(OH)2D3-treated cells in the presence of
      verapamil, whereas the A-to-B and B-to-A transport of mono(POM)-PMEA remained
      unchanged. But the verapamil and 1,25(OH)2D3 treatments failed to alter rates of
      sequential metabolism of adefovir dipivoxil in cell lysate. The composite data
      established that 1,25(OH)2D3 treatment increased both P-gp and MRP4 transport
      activities without affecting the metabolism of adefovir dipivoxil by esterases.
      Moreover, an asymmetric appearance of metabolites, being higher with apical
      application, was observed. According to the catenary model, the asymmetry is
      suggestive that esterases are predominantly localized on the apical membrane and
      within the cell.

PMID- 22387230
TI  - Combined diazepam and HDAC inhibitor treatment protects against seizures and
      neuronal damage caused by soman exposure.
AB  - The occurrence of status epilepticus (SE) is considered the main cause of brain
      lesions and morphological alterations, such as hippocampal neuron loss, that
      result in chronic epilepsy. Previous work demonstrated the convulsive and
      widespread neuropathological effects of soman, an organophosphorus compound that
      causes SE and severe recurrent seizures as a result of exposure. Seizures begin
      rapidly after exposure, can continue for hours, and contribute to prolonged
      physical incapacitation of the victim. This study attempts to identify
      anticonvulsive and neuroprotective drugs against soman exposure. Male Sprague
      Dawley rats were exposed to 1.0 LD(50) soman. EEGraphical and neuropathological
      (Fluoro-Jade B staining) effects were analyzed at 72 h post-exposure to soman and
      subsequent treatments with diazepam (DZP) alone or in combination with histone
      deacetylase inhibitors, suberoylanilide hydroxamic acid (SAHA) or valproic acid
      (VPA). The extent of brain damage was dependent on the length of SE and not on
      the number of recurrent seizures. DZP treatment alone decreased SE time and
      damage in hippocampus, amygdala, thalamus and cortex, but not in piriform nuclei.
      The combination of DZP and VPA 100 mg/kg showed more anticonvulsive effects,
      decreased SE time, and afforded more neuroprotection in the hippocampus, mainly
      the ventral portion. The combination DZP and SAHA 25 mg/kg was more
      neuroprotective, but not more anticonvulsant than DZP alone. The DZP combination
      with VPA HDAC inhibitor proved to be a good treatment for SE and neuronal damage
      caused by soman exposure.

PMID- 22387231
TI  - Stress management at the ER: regulators of ER stress-induced apoptosis.
AB  - The endoplasmic reticulum (ER) is an elaborate cellular organelle essential for
      cell function and survival. Conditions that interfere with ER function lead to
      the accumulation and aggregation of unfolded proteins which are detected by ER
      transmembrane receptors that initiate the unfolded protein response (UPR) to
      restore normal ER function. If the ER stress is prolonged, or the adaptive
      response fails, apoptotic cell death ensues. Many studies have focused on how
      this failure initiates apoptosis, particularly because ER stress-induced
      apoptosis is implicated in the pathophysiology of several neurodegenerative and
      cardiovascular diseases. In this review we aim to shed light on the proteins that
      are not core components of the UPR signaling pathway but which can influence the
      course of the ER stress response by regulating the switch from the adaptive phase
      to apoptosis.

PMID- 22387233
TI  - Improved biomass saccharification by Trichoderma reesei through heterologous
      expression of lacA gene from Trametes sp. AH28-2.
AB  - The Trametes sp. AH28-2 laccase gene lacA fused to cellobiohydrolase I signal
      peptide coding sequence was heterologously expressed in T. reesei. The lacA cDNA
      was under the control of the Aspergillus nidulans glyceraldehyde-3-phosphate
      dehydrogenase promoter. Native PAGE analysis indicated that two transformants, L8
      and L38, were able to secrete recombinant laccase A, and their laccase activities
      corresponding to ABTS oxidation reached 3.62 IUml(-1) and 1.50 IUml(-1)
      respectively. Most of the characteristics of the recombinant laccase were similar
      to those of the native enzyme. Reducing sugar yields of L8 and L38 obtained from
      saccharification of corn residue by crude enzyme increased by 31.3% and 71.6%
      respectively compared to the host strain. These results indicated that the
      engineering strains developed in this work could be potentially used for laccase
      production and tailoring cellulase properties with laccase proteins through
      genetic manipulation would be a feasible strategy to improve saccharification
      efficiency of biomass by cellulase preparation.

PMID- 22387234
TI  - Hospice decision making: diagnosis makes a difference.
AB  - PURPOSE: This study explored the process of decision making about hospice
      enrollment and identified factors that influence the timing of that decision.
      METHODS: This study employed an exploratory, descriptive, cross-sectional design
      and was conducted using qualitative methods. In-depth in-person semistructured
      interviews were conducted with 36 hospice patients and 55 caregivers after 2
      weeks of hospice care. The study was guided by Janis and Mann's conflict theory
      model (CTM) of decision making. Qualitative data analysis involved a directed
      content analysis using concepts from the CTM. RESULTS: A model of hospice
      enrollment decision making is presented. Concepts from the CTM (appraisal,
      surveying and weighing the alternatives, deliberations, adherence) were used as
      an organizing framework to illustrate the dynamics. Distinct differences were
      found by diagnosis (cancer vs. other chronic illness, e.g., heart and lung
      diseases) during the pre-encounter phase or before the hospice referral but no
      differences emerged during the post-encounter phase. IMPLICATIONS: Differences in
      decision making by diagnosis suggest the need for research about effective means
      for tailored communication in end-of-life decision making by type of illness.
      Recognition that decision making about hospice admission varies is important for
      clinicians who aim to provide person-centered and family-focused care.

PMID- 22387235
TI  - [Management of twin-to-twin transfusion syndrome].
AB  - Twin-to-twin transfusion syndrome (TTTS), also called twin oligoamnios
      polyhydramnios sequence (TOPS) complicates around 15% of monochorionic
      pregnancies irrespective of the mode of conception. It is a hemodynamic, and
      probably hormonal, discordance secondary to imbalanced blood flow through the
      vascular anastomoses aforementioned. During the last 15 years, a lot of progress
      has been made in the understanding, diagnosis and treatment of TTTS.
      Nevertheless, many questions remain unanswered and research is still active in
      this domain. Fetoscopic laser coagulation of placental vessels is the only
      treatment addressing the pathophysiology of the syndrome as proven through a
      randomized controlled study against amnioreduction. This technique has definitely
      improved overall survival as well as the rate of neurologically intact survival
      but it still lacks preoperative prognostic markers.

PMID- 22387232
TI  - Excessive discounting of delayed reinforcers as a trans-disease process
      contributing to addiction and other disease-related vulnerabilities: emerging
      evidence.
AB  - Delay discounting describes the devaluation of a reinforcer as a function of the
      delay until its receipt. Although all people discount delayed reinforcers, one
      consistent finding is that substance-dependent individuals tend to discount
      delayed reinforcers more rapidly than do healthy controls. Moreover, these higher
      than-normal discounting rates have been observed in individuals with other
      behavioral maladies such as pathological gambling, poor health behavior, and
      overeating. This suggests that high rates of delay discounting may be a trans
      disease process (i.e., a process that occurs across a range of disorders, making
      findings from one disorder relevant to other disorders). In this paper, we argue
      that delay discounting is a trans-disease process, undergirded by an imbalance
      between two competing neurobehavioral decision systems. Implications for our
      understanding of, and treatment for, this trans-disease process are discussed.

PMID- 22387236
TI  - Neurotrophin production in brain pericytes during hypoxia: a role of pericytes
      for neuroprotection.
AB  - Neurotrophins are crucial regulators of neuronal survival and death. Evidence
      suggests that cells comprising the neurovascular unit (NVU) cooperatively mediate
      neuronal development, survival and regeneration. The aim of this study was to
      test whether cerebrovascular cells, endothelial cells and pericytes, produce
      neurotrophins and play neuroprotective roles during hypoxic insults. We examined
      the expression of neurotrophins and their receptors in cultured human cerebral
      microvascular endothelial cells and pericytes, astrocytes and the rat neuronal
      cell line PC12. Differentiated PC12 cells expressed TrkA, the NGF receptor, which
      was significantly upregulated by hypoxia at 1% O(2) and regulated neuronal
      survival. Both pericytes and astrocytes expressed three neurotrophins, i.e. NGF,
      BDNF and NT-3, while TrkB and TrkC, specific receptors for BDNF and NT-3, were
      expressed in astrocytes, but not pericytes. In response to hypoxia, among the
      neurotrophins expressed in pericytes and astrocytes only NT-3 expression was
      significantly upregulated in pericytes. Treatment of astrocytes with NT-3
      significantly activated Erk1/2 and increased the expression of NGF both at mRNA
      and protein levels. The MEK1 inhibitor U0126 or siRNA-mediated knockdown of TrkC
      abolished the NT-3-induced upregulation of NGF in astrocytes. Taken together,
      cerebral microvascular pericytes and astrocytes are potent producers of
      neurotrophins in the NVU. In response to hypoxia, pericytes increase NT-3
      production, which induces astrocytes to increase NGF production through the TrkC
      Erk1/2 pathway. The interplay between pericytes and astrocytes through
      neurotrophins in the NVU may play an important role in neuronal survival under
      hypoxic conditions.

PMID- 22387237
TI  - Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several
      unrelated families: long-term follow-up in one kindred.
AB  - Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the
      sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic
      rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate
      wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels,
      hypercalciuria, rickets/osteomalacia, and frequently kidney stones or
      nephrocalcinosis. Similar albeit less severe biochemical changes are also
      observed in heterozygous carriers, which are furthermore indistinguishable from
      those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3
      mutations (exons and introns) in two previously not reported HHRH kindreds, which
      resulted in the identification of three novel mutations. The affected members of
      kindred A were compound heterozygous for two different mutations, c.1046_47del
      and the intronic mutation c.560+23_561-42del, while the index case in kindred B
      was homozygous for the nonsense SLC34A3 mutation c.1764C>G (p.Y588X). The patient
      in kindred C was diagnosed with IH because of bilateral medullary
      nephrocalcinosis, suppressed PTH levels, and hypercalciuria; she was found to
      have a novel heterozygous c.1571_1880del mutation. The HHRH patients in kindred A
      were treated for up to 7years with oral phosphate, which led to reversal of
      hypophosphatemia, hypercalciuria, and prevention or healing of the mild bone
      abnormalities. PTH levels were normal throughout the observation period, while
      1,25(OH)(2) vitamin D levels remained elevated and may thus be helpful for
      assessing treatment efficacy and patient compliance in HHRH.

PMID- 22387239
TI  - [Postprandial hypoglycemia].

PMID- 22387240
TI  - Actin filament tracking in electron tomograms of negatively stained lamellipodia
      using the localized radon transform.
AB  - The aim of this work was to develop a protocol for automated tracking of actin
      filaments in electron tomograms of lamellipodia embedded in negative stain. We
      show that a localized version of the Radon transform for the detection of
      filament directions enables three-dimensional visualizations of filament network
      architecture, facilitating extraction of statistical information including
      orientation profiles. We discuss the requirements for parameter selection set by
      the raw image data in the context of other, similar tracking protocols.

PMID- 22387238
TI  - The role of synovitis in osteoarthritis pathogenesis.
AB  - Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage
      and peri-articular bone, but there is increasing recognition that OA affects all
      of the joint tissues, including the synovium (SM). Under normal physiological
      conditions the synovial lining consists of a thin layer of cells with phenotypic
      features of macrophages and fibroblasts. These cells and the underlying
      vascularized connective tissue stroma form a complex structure that is an
      important source of synovial fluid (SF) components that are essential for normal
      cartilage and joint function. The histological changes observed in the SM in OA
      generally include features indicative of an inflammatory "synovitis";
      specifically they encompass a range of abnormalities, such as synovial lining
      hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and
      fibrosis. The pattern of synovial reaction varies with disease duration and
      associated metabolic and structural changes in other joint tissues. Imaging
      modalities including magnetic resonance (MRI) and ultrasound (US) have proved
      useful in detecting and quantifying synovial abnormalities, but individual
      studies have varied in their methods of evaluation. Despite these differences,
      most studies have concluded that the presence of synovitis in OA is associated
      with more severe pain and joint dysfunction. In addition, synovitis may be
      predictive of faster rates of cartilage loss in certain patient populations.
      Recent studies have provided insights into the pathogenic mechanisms underlying
      the development of synovitis in OA. Available evidence suggests that the
      inflammatory process involves engagement of Toll-like receptors and activation of
      the complement cascade by degradation products of extracellular matrices of
      cartilage and other joint tissues. The ensuing synovial reaction can lead to
      synthesis and release of a wide variety of cytokines and chemokines. Some of
      these inflammatory mediators are detected in joint tissues and SF in OA and have
      catabolic effects on chondrocytes. These inflammatory mediators represent
      potential targets for therapeutic interventions designed to reduce both symptoms
      and structural joint damage in OA. This article is part of a Special Issue
      entitled "Osteoarthritis".

PMID- 22387241
TI  - Integrated pharmacokinetics of major bioactive components in MCAO rats after oral
      administration of Huang-Lian-Jie-Du-Tang.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang (HLJDT, or Oren-gedoku-to
      in Japanese), an important multi-herb remedy in China and other Asia countries,
      has been used clinically to treat cerebral ischemia for decades. MATERIALS AND
      METHODS: According to the previous studies we have reported, an HPLC method was
      developed and validated for determination of berberine, palmatine, baicalin,
      baicalein and geniposide simultaneously in MCAO rat plasma after administration
      of HLJDT aqueous extract. A classified integral pharmacokinetic method was put
      forward after having compared the integrated concentration-time profile with that
      of single component. An AUC based weighting approach was used for integrated
      principle. RESULTS: The results indicated the classified integral pharmacokinetic
      profile of index components from HLJDT could reveal the pharmacokinetic behavior
      of original components, and was corresponding to the holistic pharmacological
      effects of anti-ischemia with HLJDT. CONCLUSIONS: This study was aimed to explore
      an approach that could be applied to integrate the pharmacokinetic behavior of
      different components derived from HLJDT. The integrated pharmacokinetic results
      also provided more information for further understanding of the clinical
      cerebrovascular disease in use of HLJDT.

PMID- 22387242
TI  - Standards of occupational and environmental health nursing.

PMID- 22387245
TI  - Occupational health nursing interventions to reduce third-party liability in
      workplace injuries.
AB  - This article explores general principles of workers' compensation law and the
      ability to sue third parties for employee injuries by using case law and the
      treatise Larson's Workers' Compensation Law. This overview provides occupational
      health nurses with a background on workers' compensation law, who is liable for
      employee injuries, and how recovery from third parties is distributed between the
      employer or insurer and the employee. The author then explores interventions that
      occupational health nurses can implement to reduce employee injury and employer
      costs for providing workers' compensation. The goal of this article is to
      stimulate occupational health nurses' critical-thinking and problem-solving
      skills so they may identify risks and implement cost-effective solutions that
      will prevent injuries to employees.

PMID- 22387246
TI  - Exploring occupational health nursing in South America through Brazilian
      experience.
AB  - Occupational health nursing is a well-established nursing specialty in many
      western and developed nations around the world. However, it is still considered a
      relatively new field in less industrialized countries, including those in South
      America. This article describes occupational health nursing in South America,
      primarily Brazil, with the goal of increasing understanding of the region and
      stimulating new thinking, linkages, and collaboration among occupational health
      nurses from different parts of the world. This article also gives an overview of
      the region, including population demographics, industry and economy, occupational
      risks, regional policies on occupational health, and training and education of
      occupational health and safety professionals. Occupational health nursing will
      continue to grow in South America. By collaborating with occupational health
      educators, researchers, and practitioners from developed countries, occupational
      health nurses in South America will advance the professional specialty.

PMID- 22387247
TI  - Occupational health nursing in the United States.
AB  - This article is a summary of information about occupational health nurses and
      occupational health nursing in the United States. The article provides
      demographic, education, credentialing, role, and other data based on secondary
      analysis of occupational health nurses' responses to the 2008 National Sample
      Survey of Registered Nurses. Current issues affecting the U.S. work force and
      businesses are addressed and high-risk business and industrial sectors are noted.
      Occupational health nurse practice opportunities are highlighted and practice
      areas where occupational health nursing research is currently focused are
      discussed. The article also examines the challenges facing the next generation of
      occupational health nurses.

PMID- 22387249
TI  - Methicillin-Resistant Staphylococcus aureus (MRSA).
AB  - Occupational and environmental health nurses can prevent the spread of MRSA when
      evaluating and treating workers' injuries.

PMID- 22387250
TI  - Clinicians poorly assess health literacy-related readiness for transition to
      adult care in adolescents with inflammatory bowel disease.
AB  - BACKGROUND & AIMS: To prepare for the transition from pediatric to adult-oriented
      health care systems, adolescents must develop the ability to obtain, process, and
      understand basic health information; make appropriate health decisions; and
      interact effectively with health care professionals. However, physicians use
      subjective methods to determine patients' readiness for this transition. We
      investigated health care literacy-related readiness for transition of children
      and adolescents with inflammatory bowel disease (IBD) to identify determinants
      and compare actual levels with clinicians' opinions. METHODS: The study included
      74 pediatric patients with IBD >=10 years old who were recruited from a pediatric
      hospital-based clinic. We evaluated their functional and interactive health
      literacy and recorded clinicians' perceptions of literacy and readiness for
      transition among pediatric patients. Relationships between health literacy
      measures, demographic variables, and clinician perceptions were determined.
      RESULTS: Health literacy-related readiness for transition was observed in 11% of
      the patients analyzed. However, clinicians found 47% of the cohort ready for the
      transition, on the basis of literacy standards. Health literacy-related readiness
      for transition was associated with older age (P < .01), white race (P = .03), and
      low income (P < .02). Agreement was poor between measures-defined and clinician
      defined levels of health literacy-related readiness for transition (P = .18).
      CONCLUSIONS: Clinicians inadequately judge the health literacy-related readiness
      for transition to adult care of pediatric IBD patients. Improved awareness of
      health literacy issues among adolescents with IBD is needed among health care
      providers and health care systems.

PMID- 22387251
TI  - Duodenal metastasis of cervical adenosquamous carcinoma.

PMID- 22387252
TI  - Common features of patients with autoimmune atrophic gastritis.
AB  - BACKGROUND & AIMS: Autoimmune atrophic gastritis (AIG) is characterized by immune
      mediated chronic inflammation of the gastric body and fundus, leading to hypo
      achlorhydria and vitamin B12 deficiency. We analyzed the clinical features of AIG
      and sought to identify factors that might be used in diagnosis. METHODS: We
      collected and analyzed clinical data from 99 consecutive patients (age, 59 +/- 17
      y) who were diagnosed with AIG, based on histologic factors and the presence of
      autoantibodies against gastric parietal cells. RESULTS: Clinical factors that led
      to a diagnosis of AIG included hematologic findings related to vitamin B12
      deficiency (n = 37), incidental histologic evidence in gastric biopsy specimens
      (n = 34), immune disorders (n = 18; 9 were celiac disease), neurologic symptoms
      (n = 6), and a family history of AIG (n = 4). CONCLUSIONS: Based on an analysis
      of 99 consecutive patients with AIG, this disorder is not solely a condition of
      the elderly. Other features to look for in making a diagnosis of AIG include
      vitamin B12 deficiency, histologic factors, and immune disorders.

PMID- 22387253
TI  - Optimal length of anticoagulant therapy in cirrhotic patients with portal vein
      thrombosis.

PMID- 22387254
TI  - Association between volume of endoscopic retrograde cholangiopancreatography at
      an academic medical center and use of pancreatobiliary therapy.
AB  - BACKGROUND & AIMS: Many advances have been made in pancreatobiliary imaging and
      endoscopy techniques. However, little is known about trends in use of endoscopic
      retrograde cholangiopancreatography (ERCP). METHODS: We performed a retrospective
      cohort study that analyzed data from 33,596 ERCPs performed at Indiana University
      Medical Center from 1994 to 2009. Data from all patients were entered into an
      endoscopy database. We compared changes in patient demographics, indications for
      ERCP, and utilization of specific ERCP therapies during this time period.
      RESULTS: The annual volume of ECRP increased steadily from 1175 in 1994 to 2802
      in 2009 (P < .0001). Of all patients, 33.9% had previously undergone an ERCP at a
      different facility; 42.3% of these were unsuccessful. The odds of having
      undergone a failed ERCP at another facility increased slightly each year (odds
      ratio, 1.02; P < .001). Among patients who had a failed ERCP elsewhere, the
      success rate at Indiana University Medical Center was 96.1%. The frequency of
      patients with American Society of Anesthesiologists class >=3 (odds ratio, 1.12;
      P < .001) who received anesthesia-administered sedation increased each year (odds
      ratio, 1.25; P < .001). Most ERCPs were performed for common bile duct stones or
      strictures and suspected sphincter of Oddi dysfunction (77.2%). The most rapid
      increase was among procedures for common bile duct strictures or leaks,
      pancreatic duct stones or strictures, and suspected sphincter of Oddi
      dysfunction. Rates of biliary sphincterotomy did not change (P = .252), but the
      frequency of pancreatic sphincterotomy, common bile duct, or pancreatic duct
      stent placement and pancreatic duct stricture dilation increased during this time
      (P < .001 for each). CONCLUSIONS: At a referral center, ERCP has become
      increasingly complex. From 1994 to 2009, increasing numbers of ERCPs have been
      performed for patients with more comorbidities, higher-grade disease, history of
      failed ERCPs, and on those receiving endotherapy.

PMID- 22387255
TI  - Nonalcoholic fatty liver disease and cardiovascular disease risk.

PMID- 22387256
TI  - A 42-year-old woman with a new diagnosis of sclerosing cholangitis.

PMID- 22387258
TI  - Functional brain mapping of conscious rats during reward anticipation.
AB  - Functional magnetic resonance imaging (fMRI) in humans and non-primates has been
      useful to clarify the brain regions involved in the psychological process such as
      the reward anticipation. However, there is still no report of the fMRI study on
      the reward prediction in rodents. This is mainly because of the problem of
      anesthesia in rodent fMRI. In this study, we first developed awake fMRI method to
      investigate the brain region involved in reward anticipation in rats. After fMRI
      adaptation training, rats received light stimulation 1min before intraperitoneal
      infusion of ethanol solution (4g/kg body weight) in the MRI bore. Five or six
      days after the start of the experiment, the caudate-putamen, anterior insular
      cortex, hippocampus, ventral pallidum, nucleus accumbens and medial preoptic area
      were activated during light presentation. In contrast, no activation was observed
      in the control group. These results indicate the availability of awake fMRI
      method to investigate neural plasticity in the psychological process, learning,
      and memory such as the reward anticipation.

PMID- 22387259
TI  - The extraction of LRP via functional data analysis techniques.
AB  - A new strategy based on functional data analysis (FDA) techniques is proposed to
      extract the lateralized readiness potential (LRP), which treats
      electroencephalographic data as functional data. This FDA-based method combines
      longitudinal information from each trial (time series data) with cross-sectional
      information from all trials at a fixed time point (cross-sectional data). The
      comparison results show that the FDA-based LRP is closer to the assumed true LRP
      and is more robust against a reduction in the number of trials than the
      traditional average-based LRP. Furthermore, the results indicate that the onset
      of an FDA-based LRP is more accurate than that of an average-based LRP under
      several measuring criteria.

PMID- 22387260
TI  - Efficient genetic manipulation of 1321N1 astrocytoma cells using lentiviral gene
      transfer.
AB  - 1321N1 astrocytoma cells are frequently used to analyze stimulus-induced
      intracellular signaling. These experiments require genetic manipulation of the
      cells and several chemical and physical methods have been employed in the past.
      Recently, microporation has been suggested as the best method to transfect 1321N1
      astrocytoma cells. Here, we demonstrate that lentiviral gene transfer into 1321N1
      cells is highly efficient, cheap and non-toxic. In addition, lentiviral gene
      transfer efficiently facilitates stable expression of small hairpin RNAs.
      Finally, lentiviral gene transfer can be used to implant promoter/luciferase
      reporter genes into the chromatin of the cells, allowing promoter studies using
      templates that are embedded into the nucleosomal structure of the chromatin.

PMID- 22387261
TI  - An accurate skull stripping method based on simplex meshes and histogram analysis
      for magnetic resonance images.
AB  - Skull stripping methods are designed to eliminate the non-brain tissue in
      magnetic resonance (MR) brain images. Removal of non-brain tissues is a
      fundamental step in enabling the processing of brain MR images. The aim of this
      study is to develop an automatic accurate skull stripping method based on
      deformable models and histogram analysis. A rough-segmentation step is used to
      find the optimal starting point for the deformation and is based on thresholds
      and morphological operators. Thresholds are computed using comparisons with an
      atlas, and modeling by Gaussians. The deformable model is based on a simplex mesh
      and its deformation is controlled by the image local gray levels and the
      information obtained on the gray level modeling of the rough-segmentation. Our
      Simplex Mesh and Histogram Analysis Skull Stripping (SMHASS) method was tested on
      the following international databases commonly used in scientific articles:
      BrainWeb, Internet Brain Segmentation Repository (IBSR), and Segmentation
      Validation Engine (SVE). A comparison was performed against three of the best
      skull stripping methods previously published: Brain Extraction Tool (BET), Brain
      Surface Extractor (BSE), and Hybrid Watershed Algorithm (HWA). Performance was
      measured using the Jaccard index (J) and Dice coefficient (kappa). Our method
      showed the best performance and differences were statistically significant
      (p<0.05): J=0.904 and kappa=0.950 on BrainWeb; J=0.905 and kappa=0.950 on IBSR;
      J=0.946 and kappa=0.972 on SVE.

PMID- 22387262
TI  - Semi-supervised spike sorting using pattern matching and a scaled Mahalanobis
      distance metric.
AB  - Sorting action potentials (spikes) from tetrode recordings can be time consuming,
      labor intensive, and inconsistent, depending on the methods used and the
      experience of the operator. The techniques presented here were designed to
      address these issues. A feature related to the slope of the spike during
      repolarization is computed. A small subsample of the features obtained from the
      tetrode (ca. 10,000-20,000 events) is clustered using a modified version of k
      means that uses Mahalanobis distance and a scaling factor related to the cluster
      size. The cluster-size-based scaling improves the clustering by increasing the
      separability of close clusters, especially when they are of disparate size. The
      full data set is then classified from the statistics of the clusters. The
      technique yields consistent results for a chosen number of clusters. A MATLAB
      implementation is able to classify more than 5000 spikes per second on a modern
      workstation.

PMID- 22387263
TI  - The contribution of a murine CNS-TB model for the understanding of the host
      pathogen interactions in the formation of granulomas.
AB  - Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB,
      characterized morphologically by brain granulomas and tuberculous meningitis
      (TBM). Experimental strategies for the study of the host-pathogen interaction
      through the analysis of granulomas and its intrinsic molecular mechanisms could
      provide new insights into the neuropathology of TB. To verify whether cerebellar
      mycobacterial infection induces the main features of the disease in human CNS and
      better understand the physiological mechanisms underlying the disease, we
      injected bacillus Calmette-Guerin (BCG) into the mouse cerebellum. BCG-induced
      CNS-TB is characterized by the formation of granulomas and TBM, a build up of
      bacterial loads in these lesions, and microglial recruitment into the lesion
      sites. In addition, there is an enhanced expression of signaling molecules such
      as nuclear factor-kappaB (NF-kappaB) and there is a presence of inducible nitric
      oxide synthase (iNOS) in the lesions and surrounding areas. This murine model of
      cerebellar CNS-TB was characterized by cellular and biochemical immune responses
      typically found in the human disease. This model could expand our knowledge about
      granulomas in TB infection of the cerebellum, and help characterize the
      physiological mechanisms involved with the progression of this serious illness
      that is responsible for killing millions people every year.

PMID- 22387264
TI  - Masson's tumor in the ulnar artery.
AB  - A healthy 30-year-old woman presented to the emergency department with a
      pulsatile right forearm mass and numbness of her fourth and fifth fingers. Duplex
      scan imaging revealed an ulnar artery aneurysm with intramural thrombus. After
      resection, histopathology revealed intravascular papillary endothelial
      hyperplasia, also known as Masson's tumor, a rare but benign vascular neoplasm.
      Local resection of the tumor with vascular reconstruction is curative and
      resulted in resolution of her neurologic symptoms. To our knowledge, this is the
      first reported case of a Masson's tumor occurring in an ulnar artery.

PMID- 22387265
TI  - Risk factors for unfavorable outcome of pulmonary tuberculosis in adults in
      Taipei, Taiwan.
AB  - This study was undertaken to identify factors associated with unfavorable
      outcomes in patients with pulmonary tuberculosis (PTB) in Taipei, Taiwan in 2007
      2008. Taiwanese adults with culture-positive PTB diagnosed in Taipei during the
      study period were included in this retrospective cohort study. Unfavorable
      outcomes were classified as treatment default, death, treatment failure, or
      transfer. Of 1616 eligible patients, 22.6% (365) had unfavorable outcomes, mainly
      death. After controlling for patient sociodemographic factors, clinical findings,
      and underlying disease, independent risk factors for unfavorable outcomes
      included advanced age, unemployment, end-stage renal disease requiring dialysis,
      malignancy, acid-fast bacilius smear-positivity, multidrug-resistant TB, and
      notification from ordinary ward or intensive care unit. In contrast, patients
      receiving directly observed treatment, and with a high school or higher education
      were significantly less likely to have unfavorable outcomes. This study advanced
      our understanding by revealing that a high school or higher education might lower
      the risk of an unfavorable outcome. Our results also confirmed the risk factors
      for unfavorable outcomes shown in previous research. Future TB control programmes
      in Taiwan should target particularly high-risk patients including those who had
      lower educational levels.

PMID- 22387266
TI  - Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells
      through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and
      PKC signaling pathways.
AB  - Advanced cancer is a multifactorial disease which complicates treatment if the
      cancer cells have metastasized calling for the targeting of multiple cellular
      pathways. Gallic acid (GA) is known to possess multiple pharmacological activity
      including antitumor effects. This study investigated the mechanisms for the
      anticancer properties of GA on migration and invasion of human osteosarcoma U-2
      OS cells. The migration and invasion in U-2 OS cells were determined by a Boyden
      chamber transwell assay. The expression levels and activities of MMP-2 and MMP-9
      were measured by Western blotting, real-time PCR and gelatin zymography assays.
      All examined proteins levels from Western blotting indicated that GA decreased
      the protein levels of GRB2, PI3K, AKT/PKB, PKC, p38, ERK1/2, JNK, NF-kappaB p65
      in U-2 OS cells. GA also inhibited the activities of AKT, IKK and PKC by in vitro
      kinase assay. GA suppressed the migration and invasive ability of U-2 OS cells,
      and it decreased MMP-2 and MMP-9 protein and mRNA levels and secreted enzyme
      activities in vitro. These results suggest that potential signaling pathways of
      GA-inhibited migration and invasion in U-2 OS cells may be due to down-regulation
      of PKC, inhibition of mitogen-activated protein kinase (MAPK) and PI3K/AKT,
      resulting in inhibition of MMP-2 and MMP-9 expressions.

PMID- 22387267
TI  - The extract of Chrysanthemum indicum Linne inhibits EBV LMP1-induced NF-kappaB
      activation and the viability of EBV-transformed lymphoblastoid cell lines.
AB  - Epstein-Barr virus (EBV) latent infection transforms B lymphocytes into
      proliferating lymphoblastoid cell lines (LCLs). EBV latent infection membrane
      protein 1 (LMP1) is required for EBV-mediated B lymphocyte transformation, and
      LMP1-induced NF-kappaB activation is essential for LCL survival. To identify a
      novel inhibitor candidate for LMP1-induced NF-kappaB activation, crude ethanol
      extracts of medicinal plants were screened for the potential NF-kappaB inhibitory
      activity. Seventy percent ethanol extract of Chrysanthemum indicum Linne extract
      (CIE) strongly reduced LMP1-induced NF-kappaB activation. In addition, CIE
      inhibited LMP1-induced IKKalpha or IKKbeta activation. Interestingly, CIE
      treatment rapidly reduced LCL viability without exhibiting any adverse effects on
      the viability of human foreskin fibroblasts (HFF), EBV negative Burkitt's
      lymphoma cell lines (BL41) or HeLa cells. Taken together, CIE has potent
      inhibitory effect on EBV LMP1-induced NF-kappaB activation and EBV-transformed
      LCL viability.

PMID- 22387268
TI  - Hypoglycemic and antioxidative effects of hydroxyethyl methylcellulose in mice
      fed with high fat diet.
AB  - The effect of hydroxyethyl methylcellulose (HEMC) with different viscosities on
      the glucose metabolism and antioxidative defense system in high fat-fed mice was
      investigated. The mice were randomly divided into five dietary groups: normal
      control diet (NC), high fat diet (HF), and high fat diet supplemented with high
      viscosity (HF-HV), moderate viscosity (HF-MV), and low viscosity (HF-LV) HEMC
      fibers. After 6 weeks, the HF group showed a marked increase in body weight gain,
      body fat, blood glucose concentration, insulin level, and erythrocyte lipid
      peroxidation rate relative to the NC group. However, supplementation of HEMC in
      the diet suppressed these high fat-induced hyperglycemia and oxidative stress
      through enhancement of the activities of hepatic glucokinase and antioxidant
      enzymes. The hypoglycemic and antioxidative effects increased with increased
      viscosity of the HEMC consumed. These results illustrate that HEMC with high
      viscosity may be useful in the management of high fat diet-induced hyperglycemia
      and oxidative stress.

PMID- 22387269
TI  - Distinct MAPK pathways are involved in IL-23 production in dendritic cells
      cocultured with NK cells in the absence or presence of angiotensin II.
AB  - Accumulated evidence suggests that the crosstalk between dendritic cells (DCs)
      and natural killer (NK) cells enhances each other's capacity, and results in the
      production of a variety of soluble factors. However, little is known about the
      effect of DC-NK crosstalk in interleukin-23 (IL-23) production. In the present
      study we show that DC-NK coculture caused a high expression of IL-23, angiotensin
      II (Ang II) alone moderately increased IL-23 production in DCs, but decreased IL
      23 secretion in the DC-NK coculture system. We found that Ang II does not
      influence DC maturation in DC-NK crosstalk. We next investigated the mitogen
      activated protein kinase (MAPK) pathway in DCs. We found that Ang II increased IL
      23 production through the extracellular signal-related kinase (ERK) pathway. All
      three MAPK members c-Jun N-terminal kinase (JNK), ERK and p38 were involved in IL
      23 production in the DC-NK coculture system. In the presence of Ang II, only the
      JNK pathway seems to play a role in IL-23 production in DCs cocultured with NK.
      These data suggest that distinct MAPK pathways are involved in IL-23 production
      in DCs in response to different stimuli. This work demonstrates for the first
      time that IL-23 is produced in the DC-NK coculture system, and that Ang II is
      involved in DC-NK crosstalk. This data will act as a resource that allows further
      exploitation of role of immune response in atherosclerosis.

PMID- 22387270
TI  - A new effector of lipid metabolism: complement factor properdin.
AB  - BACKGROUND: The complement system is well known for its role in innate immunity
      via the classical, the alternative and the lectin pathways, although recent
      investigations suggest expanding roles in adipose tissue. Properdin stabilizes C3
      convertase following alternative complement activation. Properdin is also present
      in adipose tissue, localized to adipocyte membranes. AIM: We evaluated the
      potential role of properdin in energy metabolism using properdin deficient (PKO)
      mice and cell based assays. RESULTS: PKO mice have a diet-dependent increase in
      weight gain compared to wild-type (WT) littermates on a high fat diet (P<0.05),
      directly related to 51% increase in relative fat mass (PKO: 35.8+/-2.2% body fat
      vs. WT: 23.6+/-2.2%, P<0.01). PKO mice have decreased energy expenditure
      (P<0.01), and altered postprandial lipid clearance (P<0.01). However glucose
      metabolism was unchanged after a glucose tolerance test vs. WT mice. In murine
      3T3-L1 adipocytes, addition of properdin had no effect on C3 or ASP production
      but almost completely inhibited the insulin-mediated stimulation of fatty acid
      uptake and incorporation into TG. Properdin had no effect on basal or insulin
      stimulated glucose transport in either 3T3-L1 adipocytes or L6 rat skeletal
      muscle cells. CONCLUSION: Thus properdin may be added to the growing list of
      complement proteins (C3, adipsin, factor B, ASP (C3adesArg), factor H, C1q and
      C3aR) which influence lipid metabolism, energy storage and insulin resistance,
      and further support the hypothesis of a dual role of complement in adipose
      tissue.

PMID- 22387271
TI  - Delaying orthostatic syncope with mental challenge: a pilot study.
AB  - At orthostatic vasovagal syncope there appears to be a sudden decline of
      sympathetic activity. As mental challenge activates the sympathetic system, we
      hypothesized that doing mental arithmetic in volunteers driven to the end point
      of their cardiovascular stability may delay the onset of orthostatic syncope. We
      investigated this in healthy male subjects. Each subject underwent a head up tilt
      (HUT)+ graded lower body negative pressure (LBNP) up to presyncope session
      (control) to determine the orthostatic tolerance time, OTT (Time from HUT
      commencement to development of presyncopal symptoms/signs). Once the tolerance
      time was known, a randomized crossover protocol was used: either 1) Repeat
      HUT+LBNP to ensure reproducibility of repeated run or 2) HUT+LBNP run but with
      added mental challenge (2 min before the expected presyncope time). Test
      protocols were separated by 2 weeks. Our studies on five male test subjects
      indicate that mental challenge improves orthostatic tolerance significantly.
      Additional mental loading could be a useful countermeasure to alleviate the
      orthostatic responses of persons, particularly in those with histories of
      dizziness on standing up, or to alleviate hypotension that frequently occurs
      during hemodialysis or on return to earth from the spaceflight environment of
      microgravity.

PMID- 22387272
TI  - Salubrinal, an endoplasmic reticulum stress blocker, modulates sleep homeostasis
      and activation of sleep- and wake-regulatory neurons.
AB  - Endoplasmic reticulum (ER) stress has been associated with the regulation of
      sleep and wake. We have previously shown that i.c.v. administration of a specific
      ER stress modulator, Salubrinal (SALUB), which inhibits global protein
      translation by blocking the dephosphorylation of eukaryotic initiation factor
      2alpha (p-eIF2alpha), increased non-rapid eye movement (NREM) sleep. Here we
      report on the relationship between ER stress response and sleep homeostasis by
      measuring the amount and intensity of homeostatic recovery sleep in response to
      the i.c.v. administration of SALUB in adult freely behaving rats. We have also
      tested the hypothesis that SALUB induces sleep by activating sleep-promoting
      neurons and inhibiting wake-promoting neurons in the basal forebrain (BF) and
      hypothalamus by quantifying the effects of SALUB treatment on c-Fos expression in
      those neuronal groups. The present study found that i.c.v. administration of
      SALUB significantly modified the homeostatic sleep response. SALUB administered
      during sleep deprivation increased sleep intensity, indicated by slow-wave
      activity (SWA), during recovery sleep, whereas its administration during recovery
      sleep increased the amount of recovery sleep. We also found that SALUB induced c
      Fos activation of GABAergic neurons in the sleep-promoting rostral median
      preoptic nucleus while simultaneously reducing c-Fos activation of wake-promoting
      lateral hypothalamic orexin-expressing neurons and magnocellular BF cholinergic
      neurons. The current findings suggest that ER stress pathway plays a role in the
      homeostatic control of NREM sleep in response to sleep deprivation and provides a
      mechanistic explanation for the sleep modulation by molecules signaling the need
      for brain protein synthesis.

PMID- 22387274
TI  - Photosynthetic performance, lipid production and biomass composition in response
      to nitrogen limitation in marine microalgae.
AB  - Increasing energy prices demand a renewable, carbon neutral, transport fuel that
      is environmentally and commercially sustainable. The interest in the production
      of microalgae as biofuels is increasing due to their high oil content, rapid
      biomass production and small foot print. In this research, marine microalgae
      Dunaliella tertiolecta (Chlorophyceae) and Thalassiosira pseudonana
      (Bacillariophyceae) were incubated in nitrogen (N)-replete medium, and then
      transferred to N-free medium for 15 and 11 days, respectively. Fluorescence
      induction and relaxation (FIRe) fluorometry and Fourier transform infrared
      spectroscopy (FTIR) were used to monitor the photosynthetic performance, lipid
      production and metabolic responses to changing N availability. Growth rates of D.
      tertiolecta and T. pseudonana were 0.84 +/- 0.16 d(-1) and 1.21 +/- 0.09 d(-),
      respectively in N-replete medium. Upon transfer to N-free medium. The growth
      rates of T. pseudonana declined rapidly, while D. tertiolecta continued to grow
      for 5 days in N-free medium before growth declined slowly. The maximum quantum
      yield of photochemistry (F(v)/F(m)) remained high initially for D. tertiolecta
      but decreased immediately after transfer to N-free media for T. pseudonana. The
      functional absorption cross section for PSII (sigma(PSII)) increased, the time
      constant for Q(A) reoxidation (tau(Qa)) and connectivity factor (p) decreased in
      parallel to the nutritional status of the microalgae. The relative protein and
      lipid content varied in response to N limitation, but carbohydrates did not
      change. Based on FTIR, D. tertiolecta and T. pseudonana produced 20-26% lipid
      when most stressed. The combination of photosynthetic efficiency and biomass
      composition monitoring provided evidence that metabolic strategies to changing
      nutrient status are species-specific.

PMID- 22387273
TI  - Aging profoundly delays functional recovery from gustatory nerve injury.
AB  - The peripheral taste system remains plastic during adulthood. Sectioning the
      chorda tympani (CT) nerve, which sends sensory information from the anterior
      tongue to the central nervous system, causes degeneration of distal fibers and
      target taste buds. However, taste function is restored after about 40 days in
      young adult rodents. We tested whether aging impacts the reappearance of neural
      responses after unilateral CT nerve injury. Taste bud regeneration was minimal at
      day 50-65 after denervation, and most aged animals died before functional
      recovery could be assessed. A subset (n=3/5) of old rats exhibited normal CT
      responses at day 85 postsectioning, suggesting the potential for efficient
      recovery. The aged taste system is fairly resilient to sensory receptor loss and
      major functional changes in normal aging. However, injury to the taste system
      reveals a surprising vulnerability in old rodents. The gustatory system provides
      an excellent model to study mechanisms underlying delayed recovery from
      peripheral nerve injury. Strategies to accelerate recovery and restore normal
      function will be of interest, as the elderly population continues to grow.

PMID- 22387275
TI  - Processing speed and executive functions in cognitive aging: how to disentangle
      their mutual relationship?
AB  - The processing-speedtheory and the prefrontal-executivetheory are competing
      theories of cognitive aging. Here we used a theoretically and methodologically
      driven framework to investigate the relationships among measures classically used
      to assess these two theoretical constructs. Twenty-eight young adults (18-32
      years) and 39 healthy older adults (65-80 years) performed a battery of nine
      neuropsychological and experimental tasks assessing three executive function (EF)
      components: Inhibition, Updating, and Shifting. Rate of information processing
      was evaluated via three different experimental and psychometric tests. Partial
      correlations analyses suggested that 2-Choice Reaction Time (CRT) performance is
      a more pure measure of processing speed than Digit Symbol Substitution Test
      (DSST) performance in the elderly. Hierarchical regression analyses showed that,
      although measures of processing speed and EF components share mutual variance,
      each measure was independently affected by chronological age. The unique adverse
      effect of age was more important for processing speed than for EF. The processing
      speed theory and the prefrontal-executive theory of cognitive aging were shown
      not to be mutually exclusive but share mutual variance. This implies the need to
      control for their mutual relationship before examining their unique potential
      role in the explanation of age-related cognitive declines. Caution has still to
      be taken concerning the tasks used to evaluate these theoretical constructs.

PMID- 22387276
TI  - Effects of exercise intervention on event-related potential and task performance
      indices of attention networks in children with developmental coordination
      disorder.
AB  - The study investigated whether 10-week soccer training can benefit the inhibitory
      control and neuroelectric indices in children with developmental coordination
      disorder (DCD). Fifty-one children were divided into groups of typically
      developing (TD, n=21), DCD-training (n=16), and DCD non-training (n=14)
      individuals using the for Children test, and, before and after training, were
      assessed with the visuospatial attention orienting task with their lower
      extremities, while brain event-related potentials (ERPs) were concurrently
      recorded. The results indicated that, when compared to TD children, children with
      DCD responded significantly more slowly across conditions of the visuospatial
      attention orienting task and showed a deficit of inhibitory control capacity in
      their lower extremities, whereas no group differences were observed for the
      accuracy rate. Neuroelectric data indicated that, before training, P3 amplitude
      was smaller and P3 latency was slower for both DCD groups compared to TD children
      across conditions of the visuospatial attention orienting task; after training,
      the beneficial effects were seen in the strength of inhibitory control and P3
      latency in the DCD-training group. The data suggest that soccer training resulted
      in significant improvements in ERP and task performance indices for the children
      with DCD.

PMID- 22387277
TI  - Orbital and ventromedial prefrontal cortex functioning in Parkinson's disease:
      neuropsychological evidence.
AB  - A recent paper (Zald & Andreotti, 2010) reviewed neuropsychological tasks that
      assess the function of the orbital and ventromedial portions of the prefrontal
      cortex (OMPFC). Neuropathological studies have shown that the function of the
      OMPFC should be preserved in the early stages of Parkinson's disease (PD) but
      becomes affected in the advanced stages of PD. This pattern has also been
      suggested by studies that have shown that dopaminergic drugs impair the
      performance of early PD patients in OMPFC tasks that involve reinforcement
      learning but enhance the performance of advanced PD patients. Based on these
      empirical findings, we reviewed the neuropsychological evidence of OMPFC
      functions in PD patients to test two hypotheses regarding the following: (1)
      OMPFC functions at different stages of PD; (2) different effects of dopaminergic
      drugs on OMPFC functions based on PD stage and task demand. We focused our review
      only on the neuropsychological tasks that were specific and sensitive to the
      functions of the OMPFC and that were adopted at different stages of PD, such as
      reversal learning tasks, the Iowa Gambling Task and the affective Theory of Mind
      task. We found robust empirical evidence that in early PD, OMPFC functions are
      preserved and dopaminergic drugs result in a detrimental effect when the task
      involves reinforcement learning. Further studies are needed to verify the status
      of OMPFC functions in non-demented, advanced PD and to describe the longitudinal
      course of OMPFC functions in this clinical population.

PMID- 22387278
TI  - Nanoemulsion formulation of fisetin improves bioavailability and antitumour
      activity in mice.
AB  - The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown
      antitumour activity but its administration is complicated by its low water
      solubility. Our aim was to incorporate fisetin into a nanoemulsion to improve its
      pharmacokinetics and therapeutic efficacy. Solubility and emulsification tests
      allowed to develop an optimal nanoemulsion composed of Miglyol
      812N/Labrasol/Tween 80/Lipoid E80/water (10%/10%/2.5%/1.2%/76.3%). The
      nanoemulsion had an oil droplet diameter of 153 +/- 2 nm, a negative zeta
      potential (-28.4 +/- 0.6 mV) and a polydispersity index of 0.129. The
      nanoemulsion was stable at 4  degrees C for 30 days, but phase separation
      occurred at 20  degrees C. Pharmacokinetic studies in mice revealed that the
      fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant
      difference in systemic exposure compared to free fisetin. However, when the
      fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in
      fisetin relative bioavailability was noted, compared to free fisetin.
      Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung
      carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free
      fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of
      fisetin and have shown that it could improve its relative bioavailability and
      antitumour activity.

PMID- 22387279
TI  - A mathematical model for pulsatile release: controlled release of rhodamine B
      from UV-crosslinked thermoresponsive thin films.
AB  - A controlled drug delivery system fabricated from a thermoresponsive polymer was
      designed to obtain a pulsatile release profile which was triggered by altering
      the temperature of the dissolution medium. Two stages of release behaviour were
      found: fast release for a swollen state and slow (yet significant and non
      negligible) release for a collapsed state. Six cycles of pulsatile release
      between 4  degrees C and 40  degrees C were obtained. The dosage of drug
      (rhodamine B) released in these cycles could be controlled to deliver
      approximately equal doses by altering the release time in the swollen state.
      However, for the first cycle, the swollen release rate was found to be large, and
      the release time could not be made short enough to prevent a larger dose than
      desired being delivered. A model was developed based on Fick's law which
      describes pulsatile release mathematically for the first time, and diffusion
      coefficients at different temperatures (including temperatures corresponding to
      both the fully swollen and collapsed states) were estimated by fitting the
      experimental data with the theoretical release profile given by this model. The
      effect of temperature on the diffusion coefficient was studied and it was found
      that in the range of the lower critical solution temperature (LCST), the
      diffusion coefficient increased with decreasing temperature. The model predicts
      that the effective lifetime of the system lies in the approximate range of 1-42 h
      (95% of drug released), depending on how long the system was kept at low
      temperature (below the LCST). Therefore this system can be used to obtain a
      controllable pulsatile release profile for small molecule drugs thereby enabling
      optimum therapeutic effects.

PMID- 22387280
TI  - A perivascular system releasing sirolimus prevented intimal hyperplasia in a
      rabbit model in a medium-term study.
AB  - The main complication of aortocoronary reconstruction with vein grafts is
      restenosis in the course of time. The aim was to assess the effect of a
      periadventitial polyester mesh releasing sirolimus on intimal hyperplasia of
      autologous grafts. We implanted v. jugularis ext. into a. carotis communis in
      rabbits. The vein graft was either intact, or was wrapped with a pure polyester
      mesh, or with a sirolimus-releasing mesh. Three and six weeks after surgery, the
      veins were subjected to standard histological staining and the thicknesses of the
      tunica intima, the media and the intima-media complex were measured. Wrapping the
      vein with a mesh releasing sirolimus or with a pure mesh decreased the thickness
      of the intima in comparison with a vein graft by 73 +/- 11% or 73 +/- 8% after 3
      weeks, and by 73 +/- 9% or 59 +/- 12% after 6 weeks, respectively. Sirolimus
      releasing meshes reduced the thickness of the media by 65 +/- 9% and 20 +/- 12%
      after 3 and 6 weeks. The thickness of the intima-media complex in grafts with
      sirolimus-releasing meshes decreased by 60 +/- 6% and 30 +/- 13% in comparison
      with pure PES meshes, after 3 and 6 weeks, respectively. A periadventitial
      polyester mesh releasing sirolimus has the potential to become an effective
      device in preventing vein graft restenosis.

PMID- 22387281
TI  - Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-kappaB in
      arsenite-induced cell transformation.
AB  - After acute exposure of cells to arsenic, reactive oxygen species mediate changes
      in cell behavior, including activation of proliferative signaling. For chronic
      exposure to arsenic, however, the function of reactive oxygen species in cell
      transformation remains poorly understood. Although microRNA-21 (miR-21) has been
      implicated in various aspects of carcinogenesis, its functions and molecular
      mechanisms in carcinogen-induced tumorigenesis are unclear. The purpose of this
      study was to determine if miR-21 is involved in arsenite-induced malignant
      transformation and to characterize the associated signaling pathways. During
      arsenite-induced transformation of human embryo lung fibroblast (HELF) cells, miR
      21 was upregulated, and the extracellular signal-regulated kinase (ERK)/nuclear
      factor-kappaB (NF-kappaB) signal pathway was activated. Moreover, superoxide
      radical dismutase (a scavenger of superoxide) and catalase (a scavenger of
      hydroperoxides) blocked the arsenite-induced effects in HELF cells and mouse
      embryonic fibroblasts. Blockage of ERK by the inhibitor U0126 or inhibition of NF
      kappaB p65 by siRNA or Bay 11-7082 prevented the increases in miR-21 and the
      decreases in Spry1, Pten, and Pdcd4, the target proteins of miR-21, induced by
      arsenite. As determined by a ChIP-qPCR assay, NF-kappaB p65 regulated miR-21
      expression by binding directly to the promoter of miR-21. Further, anti-miR-21
      downregulated miR-21 expression and prevented the arsenite-induced activation of
      ERK via the increase in Spry1, indicating that miR-21 has a feedback effect in
      regulating ERK activation. Overexpression of miR-21 with an miR-21 mimic and
      feedback activation of ERK and NF-kappaB via the decrease in Spry1 promoted the
      malignancy of HELF cells exposed to arsenite, but knockdown of miR-21 with anti
      miR-21 and feedback blockage of ERK and NF-kappaB activation through an increase
      in Spry1 decreased anchorage-independent growth of arsenite-transformed cells.
      Thus, the transformation of HELF cells induced by chronic exposure to arsenite is
      mediated by increased miR-21 expression, which, in turn, is mediated by reactive
      oxygen species activation of the ERK/NF-kappaB pathway.

PMID- 22387282
TI  - Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium.
AB  - Flavonoids are dietary components involved in decreasing oxidative stress in the
      vascular endothelium and thus the risk of endothelial dysfunction. However, their
      very low concentrations in plasma place this role in doubt. Thus, a relationship
      between the effective intracellular concentration of flavonoids and their
      bioactivity needs to be assessed. This study examined the uptake of physiological
      concentrations of cyanidin 3-glucoside, a widespread dietary flavonoid, into
      human vascular endothelial cells. Furthermore, the involvement of the membrane
      transporter bilitranslocase (TC No. 2.A.65.1.1) as the key underlying molecular
      mechanism for membrane transport was investigated by using purified anti-sequence
      antibodies binding at the extracellular domain of the protein. The experimental
      observations were carried out in isolated plasma membrane vesicles and intact
      endothelial cells from human endothelial cells (EA.hy926) and on an ischemia
      reperfusion model in isolated rat hearts. Cyanidin 3-glucoside was transported
      via bilitranslocase into endothelial cells, where it acted as a powerful
      intracellular antioxidant and a cardioprotective agent in the reperfusion phase
      after ischemia. These findings suggest that dietary flavonoids, despite their
      limited oral bioavailability and very low postabsorption plasma concentrations,
      may provide protection against oxidative stress-based cardiovascular diseases.
      Bilitranslocase, by mediating the cellular uptake of some flavonoids, is thus a
      key factor in their protective activity on endothelial function.

PMID- 22387283
TI  - A learning curve for living donor liver transplantation.
AB  - BACKGROUND: The number of living donor liver transplantations performed has
      increased rapidly in many Eastern transplant centres. However, the impact of the
      transplant centres' experience and learning on the transplant outcomes are not
      well established. Aim of the study was to evaluate the learning curve for living
      donor liver transplantation in our centre. METHODS: Data from 156 recipients and
      156 donors who underwent surgery were reviewed. Intraoperative data and
      postoperative outcomes of both donors and recipients were retrospectively
      analysed. Recipients and donors were divided into three groups that consisted of
      52 consecutive cases each. RESULTS: Surgical duration and intraoperative blood
      loss during donor surgery were decreased significantly between the earlier and
      the more recent cases (423+/-39 vs. 400+/-44 min and 959+/-523 vs. 731+/-278 mL,
      respectively; P<0.01). Rates of postoperative complications and functional
      changes were not statistically different amongst the three donor groups.
      Immediate complication rate of the first 52 recipients was higher than those of
      the second and third cohorts. Long-term survival rates of the three recipient
      groups were similar. CONCLUSIONS: The learning curve greatly influenced immediate
      outcomes of recipients during the early transplant period. However, it had little
      influence on donor outcome; long-term outcome improvement of recipients did not
      depend on the accumulation of experience alone.

PMID- 22387284
TI  - Comment to "Prevention of paracentesis-induced circulatory dysfunction in
      cirrhosis: standard vs half albumin doses".

PMID- 22387285
TI  - 'Volcano sign' and endoscopic mucosal resection of a villous adenoma arising from
      the appendix.

PMID- 22387286
TI  - What is the probability of being too old for salvage transplantation after
      hepatocellular carcinoma resection?
AB  - BACKGROUND: The strategy of salvage transplantation for patients with
      hepatocellular carcinoma is based on the premise that tumour recurrence will be
      still transplantable at the time of recurrence. However, patients can not only
      present non-transplantable recurrence but can also be over the age limit accepted
      for transplantation. AIMS: To measure the risk of being too old for salvage
      transplantation of patients resected for hepatocellular carcinoma within Milan
      criteria. METHODS: A Markov simulation model was developed on the basis of
      published literature. RESULTS: The risk of being too old for salvage
      transplantation depends on the time-span between age at hepatic resection and age
      limit, and the expected median waiting-time. Patients resected at an age 2 or 3
      years below the age limit carry a risk of being too old that overcomes the
      probability of receiving transplantation. Salvage strategy can cause harm that
      depends on the tumour characteristics and degree of portal hypertension, becoming
      maximal for patients with multiple tumours, clinical signs of portal hypertension
      and increased bilirubin levels. CONCLUSIONS: The best strategy to adopt should be
      balanced between the risk of being too old and the expected transplant benefit,
      but salvage strategy could be pursued if it did not turn into significant harm in
      comparison to primary transplantation.

PMID- 22387287
TI  - Double endoscopic retrograde ureteral drainage performed with a standard
      gastroscope in a cystectomized patient with a Wallace ureteroilealcutaneous
      anastomosis.

PMID- 22387288
TI  - Long term efficacy of gastric electrical stimulation in intractable nausea and
      vomiting.
AB  - BACKGROUND: Although the efficacy of gastric electrical stimulation has been
      reported in short-term studies, there is a lack of data on the long-term
      improvement of nausea and vomiting by gastric electrical stimulation in patients
      with delayed or normal gastric emptying. METHODS: Thirty-one patients were
      implanted at our centre for medically refractory severe and chronic nausea and/or
      vomiting. Patients were evaluated at baseline, 6 months then 5 years after
      implantation (mean follow-up 80+/-4 months) using a symptomatic and quality of
      life scores. KEY RESULTS: Amongst the 31 patients, 4 were lost to follow-up, 6
      explanted due to lack of improvement, and 1 patient died. Out of the 20 patients
      evaluated over 5 years, the quality of life score showed 27% improvement
      (p<0.01), including nausea (62%; p<0.01), vomiting (111%; p=0.03), satiety (158%;
      p<0.01), bloating (67%; p<0.01) and epigastric pain (43%; p=0.03). Over 5 years,
      15/20 patients reported a 50% improvement with a global satisfaction rated at
      64+/-6%. Therefore, 15/27 patients (56%) were improved by gastric electrical
      stimulation over 5 years in intention to treat. Improvement of nausea 6 months
      after implantation was predictive of 5-year success of gastric electrical
      stimulation (p=0.04). Finally, patients with delayed gastric emptying or with
      normal gastric emptying rate before surgery were similarly improved over 5 years
      (60% versus 50% respectively). CONCLUSION: Gastric electrical stimulation is safe
      and effective in the long term in patients with medically refractory nausea and
      vomiting, with an efficacy over 50% beyond 5 years in intention to treat. Gastric
      emptying measured before implantation did not influence the response rate over 5
      years.

PMID- 22387289
TI  - Molecular phylogeny and biogeography of caecilians from Southeast Asia (Amphibia,
      Gymnophiona, Ichthyophiidae), with special reference to high cryptic species
      diversity in Sundaland.
AB  - We investigated the phylogenetic relationships and estimated the history of
      species diversification and character evolution in two ichthyophiid genera:
      Caudacaecilia and Ichthyophis. We estimated the phylogenetic relationships of 67
      samples from 33 localities in Southeast Asia from 3840-bp sequences of the
      mitochondrial 12S rRNA, 16S rRNA, and cyt b genes using Bayesian inference,
      maximum likelihood, and maximum parsimony methods. The Southeast Asian samples
      formed a well-supported clade differentiated from a South Asian sample. The
      Southeast Asian clade was divided into two subclades, one containing samples from
      South China, Indochina, Malay Peninsula, and Java. The other consisted of samples
      from Borneo and the Philippines. Neither Caudacaecilia nor Ichthyophis was
      monophyletic, nor did samples with or without light stripes lateral to the body
      form clades. We found several distinct sympatric lineages and undescribed
      species, especially from Sundaland.

PMID- 22387290
TI  - Branchial and extra-branchial ammonia excretion in goldfish (Carassius auratus)
      following thermally induced gill remodeling.
AB  - Under cold acclimated conditions, goldfish (Carassius auratus) express an
      interlamellar cell mass (ILCM) which limits diffusive ion loss but may also
      impede branchial ammonia excretion (J(amm)). In the present study, goldfish were
      subjected to a 2-week 5 or 25  degrees C acclimation in order to modulate the
      degree of ILCM gill coverage and determine potential effects on J(amm). 25 
      degrees C-fish displayed gill coverage which was significantly lower than the 5 
      degrees C-fish, though the ILCM was not completely absent in these fish. 5 
      degrees C-fish demonstrated J(amm) values approximately 60% lower than those of
      25  degrees C-fish. The magnitude of anterior (branchial) J(amm) strongly
      correlated with gill coverage (r(2)=0.83), suggesting that the ILCM may impede
      branchial J(amm). Divided chamber experiments demonstrated that relative to the
      25  degrees C-fish, 5  degrees C-fish relied more upon posterior routes of
      excretion. In response to high external ammonia (HEA; 1.5mM NH(4)HCO(3))
      exposures, 25  degrees C-fish displayed ammonia uptake while 5  degrees C-fish
      maintained excretion against HEA, suggesting that the ILCM may act as a barrier
      preventing ammonia uptake. In summary, the ILCM appears to impede branchial
      J(amm), such that 5  degrees C-rely more on extra-branchial routes of excretion.
      We hypothesize that gill remodeling in these fish may be intimately tied to
      physiological adjustments on the whole-body scale.

PMID- 22387291
TI  - DNA polymerase zeta is a major determinant of resistance to platinum-based
      chemotherapeutic agents.
AB  - Oxaliplatin, satraplatin, and picoplatin are cisplatin analogs that interact with
      DNA forming intrastrand and interstrand DNA cross-links (ICLs). Replicative
      bypass of cisplatin DNA adducts requires the cooperative actions of at least
      three translesion DNA synthesis (TLS) polymerases: Poleta, REV1, and Polzeta.
      Because oxaliplatin, satraplatin, and picoplatin contain bulkier chemical groups
      attached to the platinum core compared with cisplatin, we hypothesized that these
      chemical additions may impede replicative bypass by TLS polymerases and reduce
      tolerance to platinum-containing adducts. We examined multiple responses of
      cancer cells to oxaliplatin, satraplatin, or picoplatin treatment under
      conditions where expression of a TLS polymerase was limited. Our studies revealed
      that, although Poleta contributes to the tolerance of cisplatin adducts, it plays
      a lesser role in promoting replication through oxaliplatin, satraplatin, and
      picoplatin adducts. REV1 and Polzeta were necessary for tolerance to all four
      platinum analogs and prevention of hyperactivation of the DNA damage response
      after treatment. In addition, REV1 and Polzeta were important for the resolution
      of DNA double-stranded breaks created during replication-associated repair of
      platinum-containing ICLs. Consistent with ICLs being the predominant cytotoxic
      lesion, depletion of REV1 or Polzeta rendered two different model cell systems
      extremely sensitive to all four drugs, whereas Poleta depletion had little
      effect. Together, our data suggest that REV1 and Polzeta are critical for
      promoting resistance to all four clinically relevant platinum-based drugs by
      promoting both translesion DNA synthesis and DNA repair.

PMID- 22387292
TI  - Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein
      kinase JNK involvement.
AB  - CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM)
      bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK
      activation in CXCL10 production by ASM cells from people with and without asthma.
      Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs
      ERK, p38, and JNK and transcription factor NF-kappaB, or vehicle, and stimulated
      with IL-1beta, TNF-alpha, or IFN-gamma, alone or combined (cytomix). CXCL10 mRNA
      and protein, JNK, NF-kappaB p65 phosphorylation, and Ikappa-Balpha protein
      degradation were assessed using real-time PCR, ELISA, and immunoblotting,
      respectively. Cytomix, IL-1beta, and TNF-alpha induced CXCL10 mRNA expression
      more rapidly in asthmatic than nonasthmatic ASM cells. IL-1beta and/or TNF-alpha
      combined with IFN-gamma synergistically increased asthmatic ASM cell CXCL10
      release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but
      cytomix-induced release was least affected, with only JNK and NF-kappaB
      inhibitors halving it. Notably, JNK phosphorylation was markedly less in
      asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor
      SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect
      CXCL10 mRNA stability or Ikappa-Balpha degradation. Together, the JNK and NF
      kappaB inhibitors completely inhibited their CXCL10 release. We concluded that,
      in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and
      CXCL10 gene expression was more rapid following cytomix stimulation. However, in
      both, JNK activation did not regulate early events leading to NF-kappaB
      activation. Thus JNK and NF-kappaB provide independent therapeutic targets for
      limiting CXCL10 production and mast cell migration to the ASM in asthma.

PMID- 22387293
TI  - Terminal sialic acids are an important determinant of pulmonary endothelial
      barrier integrity.
AB  - The surface of vascular endothelium bears a glycocalyx comprised, in part, of a
      complex mixture of oligosaccharide chains attached to cell-surface proteins and
      membrane lipids. Importantly, understanding of the structure and function of the
      endothelial glycocalyx is poorly understood. Preliminary studies have
      demonstrated structural differences in the glycocalyx of pulmonary artery
      endothelial cells compared with pulmonary microvascular endothelial cells. Herein
      we begin to probe in more detail structural and functional attributes of
      endothelial cell-surface carbohydrates. In this study we focus on the expression
      and function of sialic acids in pulmonary endothelium. We observed that, although
      pulmonary microvascular endothelial cells express similar amounts of total sialic
      acids as pulmonary artery endothelial cells, the nature of the sialic acid
      linkages differs between the two cell types such that pulmonary artery
      endothelial cells express both alpha(2,3)- and alpha(2,6)-linked sialic acids on
      the surface (i.e., surficially), whereas microvascular endothelial cells
      principally express alpha(2,3)-linked sialic acids. To determine whether sialic
      acids play a role in endothelial barrier function, cells were treated with
      neuraminidases to hydrolyze sialic acid moieties. Disruption of cell-cell and
      cell-matrix adhesions was observed following neuraminidase treatment, suggesting
      that terminal sialic acids promote endothelial barrier integrity. When we
      measured transendothelial resistance, differential responses of pulmonary artery
      and microvascular endothelial cells to neuraminidase from Clostridium perfringens
      suggest that the molecular architecture of the sialic acid glycomes differs
      between these two cell types. Collectively our observations reveal critical
      structural and functional differences of terminally linked sialic acids on the
      pulmonary endothelium.

PMID- 22387294
TI  - Kinase-dependent activation of voltage-gated Ca2+ channels by ET-1 in pulmonary
      arterial myocytes during chronic hypoxia.
AB  - Exposure to chronic hypoxia (CH) causes pulmonary hypertension. The
      vasoconstrictor endothelin-1 (ET-1) is thought to play a role in the development
      of hypoxic pulmonary hypertension. In pulmonary arterial smooth muscle cells
      (PASMCs) from chronically hypoxic rats, ET-1 signaling is altered, with the ET-1
      induced change in intracellular calcium concentration (Delta[Ca(2+)](i))
      occurring through activation of voltage-dependent Ca(2+) channels (VDCC) even
      though ET-1-induced depolarization via inhibition of K(+) channels is lost. The
      mechanism underlying this response is unclear. We hypothesized that activation of
      VDCCs by ET-1 following CH might be mediated by protein kinase C (PKC) and/or Rho
      kinase, both of which have been shown to phosphorylate and activate VDCCs. To
      test this hypothesis, we examined the effects of PKC and Rho kinase inhibitors on
      the ET-1-induced Delta[Ca(2+)](i) in PASMCs from rats exposed to CH (10% O(2), 3
      wk) using the Ca(2+)-sensitive dye fura 2-AM and fluorescent microscopy
      techniques. We found that staurosporine and GF109203X, inhibitors of PKC, and Y
      27632 and HA 1077, Rho kinase inhibitors, reduced the ET-1-induced
      Delta[Ca(2+)](i) by >70%. Inhibition of tyrosine kinases (TKs) with genistein or
      tyrphostin A23, or combined inhibition of PKC, TKs, and Rho kinase, reduced the
      Delta[Ca(2+)](i) to a similar extent as inhibition of either PKC or Rho kinase
      alone. The ability of PKC or Rho kinase to activate VDCCs in our cells was
      verified using phorbol 12-myristate 13-acetate and GTP-gamma-S. These results
      suggest that following CH, the ET-1-induced Delta[Ca(2+)](i) in PASMCs occurs via
      Ca(2+) influx through VDCCs mediated primarily by PKC, TKs, and Rho kinase.

PMID- 22387295
TI  - Interplay of macrophages and T cells in the lung vasculature.
AB  - In severe pulmonary arterial hypertension (PAH), vascular lesions are composed of
      phenotypically altered vascular and inflammatory cells that form clusters or
      tumorlets. Because macrophages are found in increased numbers in intravascular
      and perivascular space in human PAH, here we address the question whether
      macrophages play a role in pulmonary vascular remodeling and whether accumulation
      of macrophages in the lung vasculature could be compromised by the immune system.
      We used the mouse macrophage cell line RAW 264.7 because these cells are
      resistant to apoptosis, have high proliferative capacity, and resemble cells in
      the plexiform lesions that tend to pile up instead of maintaining a monolayer.
      Cells were characterized by immunocytochemistry with cell surface markers
      (Lycopersicon Esculentum Lectin, CD117, CD133, FVIII, CD31, VEGFR-2, and S100).
      Activated, but not quiescent, T cells were able to suppress RAW 264.7 cell
      proliferative and migration activity in vitro. The carboxyfluorescein diacetate
      labeled RAW 264.7 cells were injected into the naive Sprague Dawley (SD) rat and
      athymic nude rat. Twelve days later, cells were found in the lung vasculature of
      athymic nude rats that lack functional T cells, contributing to vascular
      remodeling. No labeled RAW 264.7 cells were detected in the lungs of immune
      competent SD rats. Our data demonstrate that T cells can inhibit in vitro
      migration and in vivo accumulation of macrophage-like cells.

PMID- 22387297
TI  - Detection of circulating tumor-associated antigen depends on the domains
      recognized by the monoclonal antibodies used: N-terminal trimmed EpCAM-levels are
      much higher than untrimmed forms.
AB  - The measurement of tumor-associated proteins is of high diagnostic value in the
      follow-up of cancer patients. Most tests ignore that various forms of the protein
      can exist; especially in epithelial cancers and the soluble receptors they
      produce. We choose EpCAM as model-antigen to analyze whether tests recognizing
      different domains of the protein give different results in patients' sera. EpCAM
      reactive autoantibodies are present in the sera of patients with colorectal
      carcinoma, however little is known about the existence and possible relevance of
      circulating soluble EpCAM protein. Most monoclonal EpCAM-antibodies recognize the
      first EGF-like repeat and fail to detect N-terminal trimmed protein. We developed
      a novel ELISA to determine the concentration of serum EpCAM with mAbs recognizing
      the second EGF-like repeat. In 59 healthy controls, EpCAM concentrations ranged
      from 232 to 8893ng/ml (mean 1525ng/ml). Levels of EpCAM in 412 patients with
      adenocarcinoma were somewhat higher with concentrations ranging from 176 to
      36,259ng/ml (mean 1971ng/ml). In direct comparison, the untrimmed protein
      specific ELISA detected lower levels and frequencies as compared to the EGFII
      specific ELISA. Only sera with less than 1MUg/ml circulating EGFII-EpCAM (66% of
      the sera) contained EpCAM-specific IgG antibodies. The absence of IgG antibodies
      in the sera with more than 1MUg/ml circulating EpCAM was not due to immune
      complex formation. Anti-EpCAM IgA and IgM antibodies did not show such a
      correlation. It will be important to assess whether the presence of high levels
      of circulating EGFII-EpCAM is associated with side effects in patients given
      immunotherapy.

PMID- 22387296
TI  - Analysis of IgG subclasses (IgG1 and IgG3) to recombinant SAG2A protein from
      Toxoplasma gondii in sequential serum samples from patients with toxoplasmosis.
AB  - The kinetics of the humoral immune response was evaluated using the recombinant
      SAG2A protein comparatively to soluble Toxoplasma antigen (STAg) by ELISA in
      sequential serum samples of patients with toxoplasmosis up to 12 months of
      illness onset. The follow up of IgM and IgA levels to STAg showed a gradual
      decrease, with the majority of patients (88%) seropositive for IgM up to 12
      months of infection, whereas IgA seropositivity was relatively low (78%) compared
      to IgM (100%) in the first 3 months of infection. The follow up of IgG and IgG1
      antibodies showed a similar increasing profile for both SAG2A and STAg, with
      slightly higher seropositivity for STAg. The kinetics of IgG3 to STAg was similar
      to that of IgG1, contrasting with the kinetics of IgG3 to SAG2A that showed high
      levels up to 6 months of infection, with continuous decreasing over the time.
      Higher IgG3 seropositivity to SAG2A than STAg was also observed in the initial
      phases of infection. A higher IgG3/IgG1 ratio for SAG2A than STAg was detected in
      the first 3 months of infection, with decreasing profile over the time. The
      associations of IgG3/IgG1 ratio>1.0 with positive IgM or IgA antibodies were
      predominantly found in the first 3 months of infection, whereas associations of
      IgG3/IgG1 ratio<1.0 with positive IgM or negative IgA antibodies were mostly
      observed from 3 to 12 months of infection. In conclusion, our results demonstrate
      a differential kinetics of IgG3 antibodies to SAG2A and STAg in patients with
      toxoplasmosis up to 12 months of infection. Also, the IgG3/IgG1 ratio to SAG2A in
      association with classical serological markers of acute phase could be potential
      tools to distinguish early acute from convalescent phases of Toxoplasma gondii
      infection.

PMID- 22387298
TI  - G-CSF-induced myeloid cells stimulated by TLR2 enhance engraftment after
      allogeneic hematopoietic stem cell transplantation.
AB  - A high frequency of G-CSF-mobilized myeloid cells (gMCs) in a donor graft
      accelerates hematopoietic recovery after peripheral blood stem cell
      transplantation (PBSCT). However, because of the limited functional efficacy of
      gMCs, repeated transfusions of gMCs are frequently required. In this study, we
      investigated a strategy to improve the functional capacity of gMCs during
      hematopoietic engraftment after allogeneic transplantation. We found that toll
      like receptor 2 (TLR2) is constitutively expressed on gMCs. Treating gMCs with
      the synthetic TLR2 ligand Pam(3)CSK(4) (PAM) dramatically enhanced IL-10 and TNF
      alpha production. However, PAM treatment does not induce substantial cellular
      maturation. Moreover, PAM treatment significantly improved gMC survival. PAM
      treated gMCs significantly promoted myeloid differentiation of donor
      hematopoietic stem cells (HSCs), resulting in accelerated engraftment after
      allogeneic transplantation. Our data suggest that TLR2-stimulated gMCs may be a
      novel cellular therapeutic for increasing the efficiency of allogeneic
      hematopoietic stem cell transplantation (HSCT) by reducing infectious
      complications associated with delayed engraftment.

PMID- 22387299
TI  - Menstrual cycle-related changes of functional cerebral asymmetries in fine motor
      coordination.
AB  - Fluctuating sex hormone levels during the menstrual cycle have been shown to
      affect functional cerebral asymmetries in cognitive domains. These effects seem
      to result from the neuromodulatory properties of sex hormones and their
      metabolites on interhemispheric processing. The present study was carried out to
      investigate whether functional cerebral asymmetries in fine motor coordination as
      reflected by manual asymmetries are also susceptible to natural sex hormonal
      variations during the menstrual cycle. Sixteen right-handed women with a regular
      menstrual cycle performed a finger tapping paradigm consisting of two conditions
      (simple, sequential) during the low hormone menstrual phase and the high estrogen
      and progesterone luteal phase. To validate the luteal phase, saliva levels of
      free progesterone (P) were analysed using chemiluminescence assays. As expected,
      normally cycling women showed a substantial decrease in manual asymmetries in a
      more demanding sequential tapping condition involving four fingers compared with
      simple (repetitive) finger tapping. This reduction in the degree of dominant
      (right) hand manual asymmetries was evident during the luteal phase. During the
      menstrual phase, however, manual asymmetries were even reversed in direction,
      indicating a slight advantage in favour of the non-dominant (left) hand. These
      findings suggest that functional cerebral asymmetries in fine motor coordination
      are affected by sex hormonal changes during the menstrual cycle, probably via
      hormonal modulations of interhemispheric interaction.

PMID- 22387300
TI  - Gut bacteria profiles of Mus musculus at the phylum and family levels are
      influenced by saturation of dietary fatty acids.
AB  - BACKGROUND: Mammalian gut microbiota have been implicated in a variety of
      functions including the breakdown of ingested nutrients, the regulation of energy
      intake and storage, the control of immune system development and activity, and
      the synthesis of novel chemicals. Previous studies have shown that feeding
      mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce
      the ratio of Bacteroidetes-to-Firmicutes, while feeding hosts a fat-restricted
      diet increases this ratio. However, few studies have investigated the
      differential effects of fatty acid type on gut bacterial profile. METHODS: Over a
      14-week period, Mus musculus were fed a diet rich in omega-3 polyunsaturated
      fatty acids (n-3 PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), or
      saturated fatty acids (SFAs). Fecal pellets were collected before and after the
      treatment period from 12 randomly selected mice (4 per treatment group).
      Bacterial DNA was extracted from the pellets and characterized by analysis of the
      hypervariable V3 region of the 16S rRNA. Nominal logistic regression models were
      used to assess shifts in microbial profile at the phylum and family levels in
      response to diet. RESULTS: A significant decrease in the proportion of phylum
      Bacteroidetes species was observed for mice fed any of the three diets over time.
      However, the SFA-rich diet group showed a significantly greater decrease in
      Bacteroidetes proportion (-28%) than did either the n-3 PUFA group (-10%) or the
      n-6 PUFA group (-12%). At the family level, a significant decrease in proportion
      of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet, and a
      significant decrease in proportion of Lachnospiraceae was observed for mice fed
      the SFA-rich diet. There was no significant effect of diet type on body mass
      change. CONCLUSION: Our results indicate that SFAs have stronger effects than
      PUFAs in shifting gut microbiota profiles toward those typical of obese
      individuals, and that dietary fatty acid saturation influences shifts in gut
      microbiota independently of changes in body mass.

PMID- 22387302
TI  - Characterization of a Tigger1 element from the genome of the American mink
      (Neovison vison).
AB  - Tigger elements belong to the Tc1/Mariner family of DNA transposons which is
      remarkably widespread in nature with homologs present in organisms as diverse as
      fungi, plants and animals. In this report, we present the nucleotide sequence of
      a defragmented Tigger1 element from the genome of the American mink. The element
      is 2,274 bp long, carries 13 bp terminal inverted repeats (TIRs) and contains the
      vestiges of two open reading frames (ORFs), one of which is similar to the
      centromere associated protein CENP B. In addition, we estimate that the genome of
      the American mink contains approximately 1000 Tigger1 elements, but find no
      evidence for the transcription of extant elements in the mink.

PMID- 22387301
TI  - The complete mitochondrial genome of Microtus fortis calamorum (Arvicolinae,
      Rodentia) and its phylogenetic analysis.
AB  - Microtus fortis is a special resource of rodent in China. It is a promising
      experimental animal model for the study on the mechanism of Schistosome japonicum
      resistance. The first complete mitochondrial genome sequence for Microtus fortis
      calamorum, a subspecies of M. fortis (Arvicolinae, Rodentia), was reported in
      this study. The mitochondrial genome sequence of M. f. calamorum (Genbank:
      JF261175) showed a typical vertebrate pattern with 13 protein coding genes, 2
      ribosomal RNAs, 22 transfer RNAs and one major noncoding region (CR region).The
      extended termination associated sequences (ETAS-1 and ETAS-2) and conserved
      sequence block 1 (CSB-1) were found in the CR region. The putative origin of
      replication for the light strand (O(L)) of M. f. calamorum was 35bp long and
      showed high conservation in stem and adjacent sequences, but the difference
      existed in the loop region among three species of genus Microtus. In order to
      investigate the phylogenetic position of M. f. calamorum, the phylogenetic trees
      (Maximum likelihood and Bayesian methods) were constructed based on 12 protein
      coding genes (except for ND6 gene) on H strand from 16 rodent species. M. f.
      calamorum was classified into genus Microtus, Arvcicolinae for the highly
      phylogenetic relationship with Microtus kikuchii (Taiwan vole). Further
      phylogenetic analysis results based on the cytochrome b gene ranged from M. f.
      calamorum to one of the subspecies of M. fortis, which formed a sister group of
      Microtus middendorfii in the genus Microtus.

PMID- 22387303
TI  - Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL; NCL1, Haltia-Santavuori disease)
      is caused by mutations in the CLN1/PPT gene which are associated with an early
      onset INCL phenotype. The most detailed descriptions of INCL have come from
      Finland and a few series have been reported from southern European countries.
      Clinical course and follow-up of six Spanish patients with INCL are reported with
      the aim of assessing the chronological evolution and severity of this disease.
      The age at disease onset ranged from 8 to 15 months. Delayed motor skills were
      the initial symptom when the disease began before 12 months of age, and ataxia
      was the first sign when the disease began later. Cognitive decline, which is
      described between 12 and 18 months of age, occurred from 16 to 20 months of age.
      In our series early stage is characterized by motor impairment, cognitive decline
      and autistic features. Visual failure may appear simultaneously with the
      neurological symptoms, leading quickly to blindness. As reported, psychomotor
      regression appeared between 2 and 3 years of age. Myoclonic jerks occurred after
      24 months of age and epilepsy was the last symptom of the disease. We report two
      novel mutations in a patient without epilepsy to date and describe the features
      of two siblings homozygous for the V181M (c.541G>A) mutation, associated with the
      most severe INCL phenotype. The clinical evolution might be helpful to identify
      patients affected by this rare disease. Early diagnosis is essential in order to
      provide genetic counselling to affected families. Our series may contribute to
      the study of the genotype-phenotype INCL correlation in the Mediterranean
      countries.

PMID- 22387304
TI  - Molecular structure, expression analysis and functional characterization of APRIL
      (TNFSF13) gene in bat (Vespertilio superans Thomas).
AB  - A proliferation-inducing ligand (APRIL) is a novel member of the tumor necrosis
      factor (TNF) superfamily, which is involved in immune regulation. In the present
      study, the full-length cDNA of APRIL (designated bAPRIL) from bat was cloned
      using RT-PCR and its biological activities have been characterized. The open
      reading frame (ORF) of this cDNA consists of 753 bases, encoding a protein of 250
      amino acids. This protein was found to contain a predicted transmembrane domain,
      a putative furin protease cleavage site, and a typical TNF homology domain
      corresponding to other, known APRIL homologs. Real-time quantitative PCR (qPCR)
      analysis indicated that bAPRIL mRNA was predominantly expressed in bat lymphoid
      tissue spleen. The SUMO-bsAPRIL was efficiently expressed in Escherichia coli
      BL21 (DE3) and confirmed by SDS-PAGE and Western blot analysis. Laser scanning
      confocal microscopy analysis showed that bsAPRIL could bind to its receptors on B
      cells. In vitro, MTT assays indicated that bsAPRIL could promote the
      survival/proliferation of mouse splenic B cells grown with anti-mouse IgM. These
      findings indicate that bsAPRIL plays an important role in the survival and
      proliferation of B cells and has functional cross-reactivity among mammalians.
      The present findings may provide valuable information for research into the
      immune system of the bat.

PMID- 22387305
TI  - Microarray expression analysis of genes and pathways involved in growth plate
      cartilage injury responses and bony repair.
AB  - The injured growth plate cartilage is often repaired by a bone bridge which
      causes bone growth deformities. Whilst previous studies have identified
      sequential inflammatory, fibrogenic, osteogenic and bone remodelling responses
      involved in the repair process, the molecular pathways which regulated these
      cellular events remain unknown. In a rat growth plate injury model, tissue from
      the injury site was collected across the time-course of bone bridge formation
      using laser capture microdissection and was subjected to Affymetrix microarray
      gene expression analysis. Real Time PCR and immunohistochemical analyses were
      used to confirm changes in levels of expression of some genes identified in
      microarray. Four major functional groupings of differentially expressed genes
      with known roles in skeletal development were identified across the time-course
      of bone bridge formation, including Wnt signalling (SFRP1, SFRP4, beta-catenin,
      Csnk2a1, Tcf7, Lef1, Fzd1, Fzd2, Wisp1 and Cpz), BMP signalling (BMP-2, BMP-6,
      BMP-7, Chrd, Chrdl2 and Id1), osteoblast differentiation (BMP-2, BMP-6, Chrd,
      Hgn, Spp1, Axin2, beta-catenin, Bglap2) and skeletal development (Chrd, Mmp9, BMP
      1, BMP-6, Spp1, Fgfr1 and Traf6). These studies provide insight into the
      molecular pathways which act cooperatively to regulate bone formation following
      growth plate cartilage injury and highlight potential therapeutic targets to
      limit bone bridge formation.

PMID- 22387306
TI  - Prophylactic pacemaker implantation in familial amyloid polyneuropathy.
AB  - BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomic dominant
      disease with a high rate of conduction disorders and increased risk of sudden
      death. Prophylactic cardiac pacing may be considered in asymptomatic patients
      with FAP. However, the potential benefits are unknown. OBJECTIVE: To document
      conduction disorders in a large series of FAP and the incidence of high-degree
      atrioventricular (AV) block in patients with prophylactic pacemaker (PM).
      METHODS: From January 1999 to January 2010, 262 patients with FAP were
      retrospectively evaluated. Prophylactic PM was implanted in patients with His
      ventricular interval >= 70 ms, His-ventricular interval >55 ms associated with a
      fascicular block, a first-degree AV block, or a Wenckebach anterograde point <=
      100 beats/min. The spontaneous AV conduction was then analyzed by temporarily
      inhibiting the PM. RESULTS: As compared with patients with prophylactic PM (n =
      100) and patients implanted given a class I/IIa indication (n = 18), the patients
      who did not require PM (n = 144) were younger and displayed less severe cardiac
      involvement. Follow-up after prophylactic PM implantation was analyzed in 95 of
      the 100 patients over 45 +/- 35 months, and a high-degree AV block was documented
      in 24 of the 95 patients (25%). The risk of high-degree AV block was higher in
      patients with first-degree AV block or Wenckebach anterograde point <= 100
      beats/min (hazard ratio 3.5; 95% confidence interval 1.2-10) while microvoltage
      on surface electrocardiogram reduced the risk (hazard ratio 0.2; 95% confidence
      interval 0.1-0.7). CONCLUSION: In FAP with conduction disorders, prophylactic PM
      implantation prevented major cardiac events in 25% of the patients over a 45
      month mean follow-up. It is suggested that prophylactic PM implantation prevented
      symptomatic bradycardia in these patients.

PMID- 22387307
TI  - Postoperative wide complex tachycardia: an alternative hypothesis.

PMID- 22387308
TI  - The acoustic expression of stress in a songbird: does corticosterone drive
      isolation-induced modifications of zebra finch calls?
AB  - Animal vocalizations convey multiple pieces of information about the sender. Some
      of them are stable, such as identity or sex, but others are labile like the
      emotional or motivational state. Only a few studies have examined the acoustic
      expression of emotional state in non-human animals and related vocal cues to
      physiological parameters. In this paper, we examined the vocal expression of
      isolation-induced stress in a songbird, the zebra finch (Taeniopygia guttata).
      Although songbirds use acoustic communication extensively, nothing is known to
      date on how they might encode physiological states in their vocalizations. We
      tested the hypothesis that social isolation in zebra finches induces a rise of
      plasma corticosterone that modifies the vocal behavior. We monitored plasma
      corticosterone, as well as call rate and acoustic structure of calls of males in
      response to the playback of female calls of varied saliences (familiar versus
      stranger) in two situations: social isolation and social housing. Social
      isolation induced both a rise in plasma corticosterone, and a range of
      modifications in males' vocal behavior. Isolated birds showed a lower vocal
      activity, an abolition of the difference of response between the two stimuli, and
      evoked calls with longer duration and higher pitch. Because some of these effects
      were mimicked after oral administration of corticosterone in socially housed
      subjects, we conclude that corticosterone could be partly responsible for the
      isolation-related modifications of calls in male zebra finches. To our knowledge,
      this is the first demonstration of the direct implication of glucocorticoids in
      the modulation of the structure of vocal sounds.

PMID- 22387309
TI  - Cdc42 is required for chondrogenesis and interdigital programmed cell death
      during limb development.
AB  - Cdc42, a member of the Rho subfamily of small GTPases, is known to be a regulator
      of multiple cellular functions, including cytoskeletal organization, cell
      migration, proliferation, and apoptosis. However, its tissue-specific roles,
      especially in mammalian limb development, remain unclear. To investigate the
      physiological function of Cdc42 during limb development, we generated limb bud
      mesenchyme-specific inactivated Cdc42 (Cdc42(fl/fl); Prx1-Cre) mice.
      Cdc42(fl/fl); Prx1-Cre mice demonstrated short limbs and body, abnormal
      calcification of the cranium, cleft palate, disruption of the xiphoid process,
      and syndactyly. Severe defects were also found in long bone growth plate
      cartilage, characterized by loss of columnar organization of chondrocytes, and
      thickening and massive accumulation of hypertrophic chondrocytes, resulting in
      delayed endochondral bone formation associated with reduced bone growth. In situ
      hybridization analysis revealed that expressions of Col10 and Mmp13 were reduced
      in non-resorbed hypertrophic cartilage, indicating that deletion of Cdc42
      inhibited their terminal differentiation. Syndactyly in Cdc42(fl/fl); Prx1-Cre
      mice was caused by fusion of metacarpals and a failure of interdigital programmed
      cell death (ID-PCD). Whole mount in situ hybridization analysis of limb buds
      showed that the expression patterns of Sox9 were ectopic, while those of Bmp2,
      Msx1, and Msx2, known to promote apoptosis in the interdigital mesenchyme, were
      down-regulated. These results demonstrate that Cdc42 is essential for
      chondrogenesis and ID-PCD during limb development.

PMID- 22387310
TI  - Structural requirements of bile acid transporters: C-3 and C-7 modifications of
      steroidal hydroxyl groups.
AB  - The apical sodium dependent bile acid transporter (ASBT) and sodium-taurocholate
      cotransporting polypeptide (NTCP) are potential prodrug targets, but the
      structural requirements for these transporters are incompletely defined. The
      objective of this study was to evaluate the effect of C-3 and C-7 substitution on
      bile acid interaction with these bile acid transporters. Nineteen bile acid
      analogs were tested against ASBT and NTCP for binding, as well as translocation.
      Results indicated that ASBT and NTCP accommodated a wide range of substituents
      for binding, but all major C-7 modifications resulted in analogs that did not
      demonstrate active uptake by either ASBT or NTCP. A C-3 modification that was not
      tolerated at C-7 still afforded translocation via ASBT and NTCP, confirming the
      relative unacceptability of C-7 modification. Both ASBT and NTCP demonstrated a
      generally similar binding potency. Results suggest that drug conjugation to the C
      3 hydroxyl group, rather than C-7, has potential to lead to a successful prodrug
      targeting ASBT and NTCP.

PMID- 22387311
TI  - Dimerization of ZIP promotes its transcriptional repressive function and
      biological activity.
AB  - Self-association of a protein to form dimer and oligomer is a general theme in
      biological control mechanism, and is increasingly understood to be an important
      step in many cellular processes, including signaling transduction, protein
      degradation and transcriptional regulation. Previously, we cloned and
      functionally characterized a gene encoded for ZIP (zinc finger and G-patch domain
      containing protein). We showed that ZIP is a novel transcription repressor that
      regulates, through recruitment of the nucleosome remodeling and deacetylase
      (NuRD) complex, a collection of functionally important genes including the
      epidermal growth factor receptor (EGFR) oncogene. The important role ZIP plays in
      controlling cell proliferation and carcinogenesis highlights the need for a
      detailed understanding of the finely mechanisms by which ZIP is regulated. Here,
      we report that ZIP forms homodimers in vitro and in vivo through its C-terminal
      domains. We demonstrated that ZIP dimerization promotes its transcriptional
      repressive activity and is essential for its DNA binding. We showed that enforced
      dimerization of ZIP suppresses EGFR expression, leading to the delay of cell
      cycle progression and the inhibition of breast cancer cell proliferation. Thus,
      our results revealed that dimerization is crucial for is transcriptional
      repressive function and biological activity and provided a finely tuned means for
      the regulation the expression of EGFR oncogene. These may shed new light on the
      EGFR-related breast carcinogenesis and offer a potential new target for breast
      cancer therapy.

PMID- 22387312
TI  - Metabolic energy-independent mechanism of internalization for the cell
      penetrating peptide penetratin.
AB  - Cellular uptake of vector peptides used for internalization of hydrophilic
      molecules into cells is known to follow two different pathways: direct
      translocation of the plasma membrane and internalization by endocytosis followed
      by release into the cytosol. These pathways differ in their energy dependence.
      The first does not need metabolic energy while the second requires metabolic
      energy. Herein we used erythrocytes and plasma membrane vesicles to study
      membrane perturbations induced by the cell penetrating peptide penetratin. The
      results show that cell penetrating peptides are able to be internalized by two
      metabolic energy-independent pathways: direct crossing of the plasma membrane and
      endocytosis-like mechanisms. The last mechanism involves the induction of
      membrane negative curvature resulting in invaginations that mimic the endosomal
      uptake in the absence of ATP. This new mechanism called "physical endocytosis" or
      "self-induced endocytosis" might explain different data concerning the
      independence or dependence on metabolic energy during cellular uptake and reveals
      the autonomous capacity of peptides to induce their internalization.

PMID- 22387314
TI  - Analysis of laser-induced heating in optical neuronal guidance.
AB  - Recently, it has been shown that it is possible to control the growth direction
      of neuronal growth cones by stimulation with weak laser light; an effect dubbed
      optical neuronal guidance. The effect exists for a broad range of laser
      wavelengths, spot sizes, spot intensities, optical intensity profiles and beam
      modulations, but it is unknown which biophysical mechanisms govern it. Based on
      thermodynamic modeling and simulation using published experimental parameters as
      input, we argue that the guidance is linked to heating. Until now, temperature
      effects due to laser-induced heating of the guided neuron have been neglected in
      the optical neuronal guidance literature. The results of our finite-element
      method simulations show the relevance of the temperature field in optical
      guidance experiments and are consistent with published experimental results and
      modeling in the field of optical traps. Furthermore, we propose two experiments
      designed to test this hypotheses experimentally. For one of these experiments, we
      have designed a microfluidic platform, to be made using standard microfabrication
      techniques, for incubation of neurons in temperature gradients on micrometer
      lengthscales.

PMID- 22387313
TI  - N-glycosylation of the mammalian dipeptidyl aminopeptidase-like protein 10
      (DPP10) regulates trafficking and interaction with Kv4 channels.
AB  - The dipeptidyl aminopeptidase-like protein 10 (DPP10) is a type II transmembrane
      protein homologue to the serine protease DPPIV/CD26 but enzymatically inactive.
      In the mammalian brain, DPP10 forms a complex with voltage-gated potassium
      channels of the Kv4 family, regulating their cell surface expression and
      biophysical properties. DPP10 is a glycoprotein containing eight predicted N
      glycosylation sites in the extracellular domain. In this study we investigated
      the role of N-glycosylation on DPP10 trafficking and functional activity. Using
      site-directed mutagenesis (N to Q) we showed that N-glycosylation occured at six
      positions. Glycosylation at these specific residues was necessary for DPP10
      trafficking to the plasma membrane as observed by flow cytometry. The surface
      expression levels of the substitutions N90Q, N119Q, N257Q and N342Q were reduced
      by more than 60%. Hence the interaction with the Kv4.3/KChIP2a channel complex
      was disrupted preventing the hastening effect of wild type DPP10 on current
      kinetics. Interestingly, N257 was crucial for this function and its substitution
      to glutamine completely blocked DPP10 sorting to the cell surface and prevented
      DPP10 dimerization. In summary, we demonstrated that glycosylation was necessary
      for both DPP10 trafficking to the cell surface and functional interaction with
      Kv4 channels.

PMID- 22387315
TI  - Insight into the neuroproteomics effects of the food-contaminant non-dioxin like
      polychlorinated biphenyls.
AB  - Recent studies showed that food-contaminant non-dioxin-like polychlorinated
      biphenyls (NDL-PCBs) congeners (PCB52, PCB138, PCB180) have neurotoxic potential,
      but the cellular and molecular mechanisms underlying neuronal damage are not
      entirely known. The aim of this study was to assess whether in-vitro exposure to
      NDL-PCBs may alter the proteome profile of primary cerebellar neurons in order to
      expand our knowledge on NDL-PCBs neurotoxicity. Comparison of proteome from
      unexposed and exposed rat cerebellar neurons was performed using state-of-the-art
      label-free semi-quantitative mass-spectrometry method. We observed significant
      changes in the abundance of several proteins, that fall into two main classes:
      (i) novel targets for both PCB138 and 180, mediating the dysregulation of CREB
      pathways and ubiquitin-proteasome system; (ii) different congeners-specific
      targets (alpha-actinin-1 for PCB138; microtubule-associated-protein-2 for PCB180)
      that might lead to similar deleterious consequences on neurons cytoskeleton
      organization. Interference of the PCB congeners with synaptic formation was
      supported by the increased expression of pre- and post-synaptic proteins
      quantified by western blot and immunocytochemistry. Expression alteration of
      synaptic markers was confirmed in the cerebellum of rats developmentally exposed
      to these congeners, suggesting an adaptive response to neurodevelopmental
      toxicity on brain structures. As such, our work is expected to lead to new
      insights into the mechanisms of NDL-PCBs neurotoxicity.

PMID- 22387316
TI  - Venomics and antivenomics profiles of North African Cerastes cerastes and C.
      vipera populations reveals a potentially important therapeutic weakness.
AB  - We report the proteomic analysis of the venom of the medically relevant snake,
      Cerastes cerastes, from Morocco, and the immunoreactivity profile of an
      experimental monospecific (CcMo_AV against Moroccan C. cerastes venom) and a
      commercial (Gamma-VIP against Tunisian C. cerastes and M. lebetina venoms)
      F(ab')(2) antivenoms towards geographic variants of C. cerastes and C. vipera
      venoms. The venom of C. cerastes is a low-complexity proteome composed of 25-30
      toxins belonging to 6 protein families, mainly targetting the hemostatic system.
      This toxin arsenal explains the clinical picture observed in C. cerastes
      envenomings. Despite geographic compositional variation, the monospecific CcMo_AV
      and the Gamma-VIP divalent antivenom produced at Institut Pasteur de Tunis,
      showed similar immunocapturing capability towards Moroccan, Tunisian, and
      Egyptian C. cerastes venom proteins. Proteins partially escaping
      immunorecognition were all identified as PLA(2) molecules. Antivenomic analysis
      showed low degree of cross-reactivity of Moroccan CcMo_AV and Tunisian Gamma-VIP
      antivenoms towards C. vipera venom toxins. This study indicates that a more
      complete therapeutic cover could be achieved by including C. vipera venom in the
      formulation of venom immunization mixtures, thereby generating a pan-Cerastes
      antivenom.

PMID- 22387317
TI  - Snake venomics of Macrovipera mauritanica from Morocco, and assessment of the
      para-specific immunoreactivity of an experimental monospecific and a commercial
      antivenoms.
AB  - Proteomic analysis of the venom of the medically relevant snake Macrovipera
      mauritanica from Morocco revealed a complex proteome composed of at least 45
      toxins from 9 protein families targeting the hemostatic system of the prey or
      victim. The toxin profile of Moroccan M. mauritanica displays great similarity,
      but also worth noting departures, with the previously reported venom proteome of
      M. lebetina from Tunisia. Despite fine compositional differences between these
      Macrovipera taxa, their overall venom phenotypes explain the clinical picture
      observed in M. mauritanica and M. lebetina envenomings. However, M. mauritanica
      venom also contains significant amounts of orphan molecules whose presence in the
      venom seems to be difficult to rationalize in the context of a predator-prey arms
      race. The paraspecific immunoreactivity of an experimental monospecific (M.
      mauritanica) antivenom and a commercial bivalent antivenom, anti-C. cerastes and
      anti-M. lebetina, against the venoms of Moroccan M. mauritanica and Tunisian M.
      lebetina, was also investigated through an affinity chromatography-based
      antivenomics approach. Both antivenoms very efficiently immunodepleted homologous
      venom toxins and displayed a high degree of paraspecificity, suggesting the
      clinical utility of the two antivenoms for treating bites of both M. mauritanica
      or M. lebetina.

PMID- 22387318
TI  - Advances in the treatment of relapsed or refractory Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma (HL) is diagnosed in 20,000 men and women annually in North
      America and Europe. Despite treatment advancements for HL resulting in an overall
      survival rate of 80%, patients with advanced stage disease continue to have
      suboptimal outcomes, with relapse rates of 30%-40%. An additional 10%-15% of
      patients present with primary refractory disease. For patients who relapse after
      initial treatment, salvage chemotherapy followed by autologous stem cell
      transplant in those with chemotherapy-sensitive disease is the standard of care.
      Patients who relapse after second-line therapy have a median survival time in the
      range of 6-36 months, and the optimal management of these patients remains
      unclear. Unfortunately, there have been no new agents approved for relapsed HL
      treatment since the 1970s. Consequently, clinical decision making in this
      population is difficult. Recently however, several agents have emerged that have
      shown clinical promise in this poor-risk population. This review discusses the
      management of these patients and also discusses several newer agents showing
      clinical promise in the treatment of HL.

PMID- 22387319
TI  - Combination of texture and color cues in visual segmentation.
AB  - The visual system can use various cues to segment the visual scene into figure
      and background. We studied how human observers combine two of these cues, texture
      and color, in visual segmentation. In our task, the observers identified the
      orientation of an edge that was defined by a texture difference, a color
      difference, or both (cue combination). In a fourth condition, both texture and
      color information were available, but the texture and color edges were not
      spatially aligned (cue conflict). Performance markedly improved when the edges
      were defined by two cues, compared to the single-cue conditions. Observers only
      benefited from the two cues, however, when they were spatially aligned. A simple
      signal-detection model that incorporates interactions between texture and color
      processing accounts for the performance in all conditions. In a second
      experiment, we studied whether the observers are able to ignore a task-irrelevant
      cue in the segmentation task or whether it interferes with performance. Observers
      identified the orientation of an edge defined by one cue and were instructed to
      ignore the other cue. Three types of trial were intermixed: neutral trials, in
      which the second cue was absent; congruent trials, in which the second cue
      signaled the same edge as the target cue; and conflict trials, in which the
      second cue signaled an edge orthogonal to the target cue. Performance improved
      when the second cue was congruent with the target cue. Performance was impaired
      when the second cue was in conflict with the target cue, indicating that
      observers could not discount the second cue. We conclude that texture and color
      are not processed independently in visual segmentation. 

PMID- 22387322
TI  - Urinary corticosterone metabolite responses to capture and handling in two
      closely related species of free-living Fijian frogs.
AB  - Studies of baseline (unstressed) and short-term corticosterone stress responses
      in free-living amphibians can provide crucial information on the physiological
      responses of different populations to environmental change. In this study, we
      compared baseline and urinary corticosterone metabolite responses of free-living
      adult males and females of two closely related Fijian frogs of the Platymantis
      genus (Family: Ceratobatrachidae). Fijian ground frogs (Platymantis vitiana) live
      on the ground while Fijian tree frogs (Platymantis vitiensis) are arboreal. We
      captured free-living frogs and applied our moderate stress protocol (5 min
      handling during urine sampling at hourly intervals), with urinary corticosterone
      metabolite concentrations measured by enzyme-immunoassay. Mean urinary
      corticosterone metabolite concentrations in male and female Fijian ground frogs
      increased from 0 to 2 h and continued to increase to peak concentrations 5-6 h
      after capture. Mean baseline corticosterone concentration was significantly
      different between sexes (higher in males than females) only for Fijian ground
      frogs. There was no significant difference between sexes in the integrated
      corticosterone responses for both species. Mean baseline and urinary
      corticosterone metabolite responses of Fijian tree frogs were lower than those of
      Fijian ground frogs. Corticosterone levels increased for 4-5 h in both species
      and began to decrease again 7 h after initial capture. Corticosterone responses
      were consistently higher for Fijian ground frogs than Fijian tree frogs.
      Individuals in both species showed markedly variable corticosterone responses
      over the 8h duration of the stressor, with some individuals showing low stress
      responses and others showing high stress responses. The magnitude of the
      corrected integrated response of the ground frogs was almost twice that of the
      tree frogs. These differences in baseline and short-term corticosterone stress
      responses between these two species could be a consequence of ecological
      differences including micro-habitat, predator interactions and/or competitive
      interactions with the introduced cane toad (Rhinella marina). Comparisons of
      corticosterone responses between populations and species provide a valuable tool
      for measuring the physiological responses of the amphibians to environmental
      change.

PMID- 22387324
TI  - Photocatalytic degradation of acridine dyes using anatase and rutile TiO2.
AB  - The adsorption and photodegradation of acridine orange (AO) and acriflavine (AF)
      dyes on two mesoporous titania crystalline phases, anatase and rutile, were
      experimentally studied. Anatase and rutile were characterized by nitrogen
      adsorption, electron scanning and transmission microscopy, and X-ray diffraction.
      The adsorption capacity of rutile was higher than that of anatase, while the
      reverse is observed for photodegradation of both dyes. The adsorption of AF on
      both adsorbents was higher than that of AO, which was related with the smaller
      size of AF molecules compared with those of AO, therefore the access of AF to the
      adsorption sites is favored.

PMID- 22387323
TI  - CD4-CD8 differentiation in the thymus: connecting circuits and building memories.
AB  - The proper choice of the CD4-helper or CD8-cytotoxic lineages by developing T
      cells is crucial for the generation of an antigen-responsive and functionally fit
      T cell repertoire. Here we present a brief overview of the transcriptional
      control of this process, with emphasis on two issues. The study of Cd4
      expression, that had previously generated important paradigms for transcriptional
      regulation in eukaryotic cells, now brings new twists to the concept of
      'epigenetic memory'. And connections are emerging between transcriptional
      regulators critical for commitment to either lineage. The present review attempts
      to integrate these findings and discusses the still elusive mechanisms that match
      CD4-CD8 lineage differentiation to MHC specificity.

PMID- 22387320
TI  - Recent developments in myofibroblast biology: paradigms for connective tissue
      remodeling.
AB  - The discovery of the myofibroblast has opened new perspectives for the
      comprehension of the biological mechanisms involved in wound healing and fibrotic
      diseases. In recent years, many advances have been made in understanding
      important aspects of myofibroblast basic biological characteristics. This review
      summarizes such advances in several fields, such as the following: i) force
      production by the myofibroblast and mechanisms of connective tissue remodeling;
      ii) factors controlling the expression of alpha-smooth muscle actin, the most
      used marker of myofibroblastic phenotype and, more important, involved in force
      generation by the myofibroblast; and iii) factors affecting genesis of the
      myofibroblast and its differentiation from precursor cells, in particular
      epigenetic factors, such as DNA methylation, microRNAs, and histone modification.
      We also review the origin and the specific features of the myofibroblast in
      diverse fibrotic lesions, such as systemic sclerosis; kidney, liver, and lung
      fibrosis; and the stromal reaction to certain epithelial tumors. Finally, we
      summarize the emerging strategies for influencing myofibroblast behavior in vitro
      and in vivo, with the ultimate goal of an effective therapeutic approach for
      myofibroblast-dependent diseases.

PMID- 22387325
TI  - Recycling of sugarcane bagasse ash waste in the production of clay bricks.
AB  - This work investigates the recycling of sugarcane bagasse ash waste as a method
      to provide raw material for clay brick bodies, through replacement of natural
      clay by up 20 wt.%. Initially, the waste sample was characterized by its chemical
      composition, X-ray diffraction, differential thermal analysis, particle size,
      morphology and pollution potential. Clay bricks pieces were prepared, and then
      tested, so as to determine their technological properties (e.g., linear
      shrinkage, water absorption, apparent density, and tensile strength). The
      sintered microstructure was evaluated by scanning electron microscopy (SEM). It
      was found that the sugarcane bagasse ash waste is mainly composed by crystalline
      silica particles. The test results indicate that the sugarcane bagasse ash waste
      could be used as a filler in clay bricks, thus enhancing the possibility of its
      reuse in a safe and sustainable way.

PMID- 22387327
TI  - The rhetoric and realities of integrating air quality into the local transport
      planning process in English local authorities.
AB  - Regardless of its intent and purposes, the first decade of the Local Air Quality
      Management (LAQM) framework had little or no effect in reducing traffic-related
      air pollution in the UK. Apart from the impact of increased traffic volumes, the
      major factor attributed to this failure is that of policy disconnect between the
      process of diagnosing air pollution and its management, thereby limiting the
      capability of local authorities to control traffic-related sources of air
      pollution. Integrating air quality management into the Local Transport Plan (LTP)
      process therefore presents opportunities for enabling political will, funding and
      joined-up policy approach to reduce this limitation. However, despite the
      increased access to resources for air quality measures within the LTP process,
      there are local institutional, political and funding constraints which reduce the
      impact of these policy interventions on air quality management. This paper
      illustrate the policy implementation gaps between central government policy
      intentions and the local government process by providing evidence of the
      deprioritisation of air quality management compared to the other shared
      priorities in the LTP process. We draw conclusions on the policy and practice of
      integrating air quality management into transport planning. The evidence thereby
      indicate the need for a policy shift from a solely localised hotspot management
      approach, in which the LAQM framework operates, to a more holistic management of
      vehicular emissions within wider spatial administrative areas.

PMID- 22387326
TI  - Understanding stakeholder participation in research as part of sustainable
      development.
AB  - Participation is often presented as a 'good' thing and a fairer way to represent
      views and opinions outside narrow confines of interest and expertise. However,
      the roots of participatory approaches within research contexts are deep and
      numerous twists and turns demonstrate a confused and possibly confusing
      morphology with significant gaps and weaknesses. In this paper 'via the medium'
      of the POINT (Policy Influence of Indicators) research project we trace elements
      of the recent history of group participation in sustainable development and the
      emergence of focus on four areas, most significantly how participatory methods
      are used. In the absence of strong evidence to contrary we suggest that the issue
      of how participants engage in participation remains a significant weakness for
      the field. In order to counter the apparent gap we suggest that a certain degree
      of structure and process can provide the oeuvre of participatory approaches with
      a higher degree of transparency in the research process and, by focus on the use
      of a method called Triple Task, group participatory events can be encouraged to
      yield greater insights into the workings of groups of all kinds.

PMID- 22387328
TI  - Performance of stormwater detention tanks for urban drainage systems in northern
      Italy.
AB  - The performance of stormwater detention tanks with alternative design
      configurations (insertion in the storm sewer network; volume per impervious
      hectare) and operating conditions (continuous and intermittent emptying rules)
      have been evaluated according to an integrated approach. Various performance
      indices have been adopted to describe the mitigation of the pollution impact to
      the natural environment, the reduction of the management and maintenance charges
      for the urban drainage system, the preservation of the normal purification
      efficiency, and the limitation of the costs at the treatment plant. The US EPA
      Storm Water Management Model has been used to simulate the rainfall-runoff
      process and the pollutant dynamics on theoretical catchments and storm sewer
      networks for an individual event, as well as for a continuous run of events and
      inter event periods of one year recorded at the rain gauge of Cascina Scala
      (Pavia, northern Italy). Also the influence of the main characteristics of the
      urban catchment and the drainage system (area of the catchment and slope of the
      network) on the performance of alternative design and operating solutions has
      been examined. Stormwater detention tanks combined with flow regulators
      demonstrated good performance with respect to environmental pollution:
      satisfactory performance indicators can be obtained with fairly low flow rates of
      flow regulators (0.5-1 L/s per hectare of impervious area) and tank volumes of
      about 35-50 m(3) per impervious hectare. Continuous emptying guaranteed the
      lowest number and duration of overflows, while an intermittent operation
      minimised the volume sent for purification reducing the costs and the risks of
      impairment in the normal treatment efficiency of the plant. Overall, simulation
      outcomes revealed that the performance indexes are scarcely affected by the area
      of the catchment and the slope of the drainage network. The result of this study
      represents a key issue for the implementation of environmental policies in large
      urban areas.

PMID- 22387329
TI  - Decision support for sustainable urban drainage system management: a case study
      of Jijel, Algeria.
AB  - This paper aims to develop a methodology to support the sustainable management of
      Urban Drainage Systems (UDSs) in Algeria. This research is motivated by the
      various difficulties that the National Sanitation Office (ONA) has in managing
      this complex infrastructure. The method mainly consists of two approaches: the
      top-down approach and the bottom-up approach. The former facilitates the
      identification of factors related to a sustainable UDS, the development
      priorities and the criteria available to managers. The latter assesses UDS
      performance using the weighted sum method to aggregate indicators or criteria
      weighted using the Analytical Hierarchy Process (AHP). The method is demonstrated
      through its application to the UDS in the city of Jijel, Algeria.

PMID- 22387330
TI  - Relationship between back muscle endurance and voluntary activation.
AB  - There is some evidence that the Biering-Sorensen endurance test can discriminate
      low back pain sufferers from healthy individuals and can predict future back
      pain. This test relies on the subject's ability to voluntarily drive the back
      muscles. This neural drive, termed voluntary activation (VA) can be measured
      using the twitch interpolation technique. The aim of the current study was to
      investigate the relationship between back muscle endurance and VA. Twenty-one
      healthy volunteers (10 males) participated. Bilateral electromyographic
      recordings were obtained from erector spinae and rectus abdominis. Back extensor
      torque was recorded using a dynamometer. The protocol consisted of measurement of
      VA (using magnetic stimulation of the brain and assessment of the sizes of the
      evoked twitches) and measurement of endurance. There was a linear correlation
      (r(2)=1, P<0.01) between voluntary torque and VA. The mean (SEM) endurance time
      was 174.9 (12.8)s. There was no correlation between endurance and VA at either
      100% MVC (r(2)=0.01, P=0.72) or at 50% MVC (r(2)=0.11, P=0.16). These findings
      indicate that the endurance of the back muscles, as assessed using this widely
      utilised test does not appear to be related to a subject's ability to drive their
      back muscles voluntarily either maximally or submaximally.

PMID- 22387331
TI  - [Kabuki syndrome].
AB  - INTRODUCTION: Kabuki syndrome (OMIM: #147 920) presents as large palpebral
      fissures with eversion of the lateral third of the lower eyelids, depressed nasal
      bridge, arched eyebrows, dysplastic ears and in most cases, with mental
      retardation. Patients have minor and major abnormalities in different systems.
      Its genetic basis is heterogeneous, but recently has been associated with
      mutations in gen MLL2. CASE REPORTS: We present two patients with clinical
      features compatibles with the syndrome, mainly: large palpebral fissures with
      eversion of the lateral third of the lower eyelids, depressed nasal bridge,
      arched eyebrows, flat nose, persistent fingertip pads, cardiopathies and renal
      anomalies. COMMENTARY: The diagnosis of this condition is clinical. The
      characteristics in the cases are compared with the patients reported in the
      literature. The importance of early diagnosis is to provide preventive management
      and an appropriate genetic counseling for the family.

PMID- 22387332
TI  - [Systematic assessment of the paediatrician's performance during simulated
      supraventricular tachycardia].
AB  - INTRODUCTION: The aims of this study are to: a) assess the quality in clinical
      management during a simulated scenario of acute supraventricular tachycardia
      (SVT) by means of a structured task-based checklist and to b) detect pitfalls and
      grey areas where reinforcement in training may be needed. MATERIAL AND METHODS:
      We systematically reviewed SVT simulated scenarios during simulation courses
      between June 2008 and April 2010. Three scenarios were programmed using
      SimBaby(r) simulation system, and included stable SVT (S-SVT), stable progressing
      to unstable SVT (SU-SVT) and unstable SVT (U-SVT). Scenarios were evaluated by
      means of an 18-task checklist based on ILCOR international recommendations.
      RESULTS: A total of 45 scenarios were assessed with the participation of 167
      paediatricians, including 15 S-SVT, 25 SU-SVT and 5 U-SVT scenarios. Out of a
      total of 551 possible tasks, 328 (59.5%) were completed correctly. The mean
      percentage of correct tasks per scenario was 63.4 (16.7) for S-SVT, 47.8 (20.3)
      for SU-ST and 38.6 (31) for U-SVT (p=0.028). There were no significant
      differences between primary care paediatricians and hospital paediatricians. Most
      of the participants correctly identified non-sinus rhythm as SVT. However,
      important pitfalls were observed, including failure to identify haemodynamic
      instability in 20 out of 43 (48%) cases, an incorrect dose of adenosine in 18 out
      of 39 (48%), incorrect adenosine administration in 23 out of 39 (59%), and non
      recognition of indication to emergent cardioversion in 15 out of 31 (48%).
      CONCLUSIONS: Paediatricians are able to diagnose SVT correctly, but need to
      improve their skills in treatment. Systematic analysis of clinical performance in
      a simulated scenario allows the identification of strengths, as well as weak
      points, where reinforcement is needed.

PMID- 22387333
TI  - [Agminated Spitz nevi].

PMID- 22387335
TI  - Development and evaluation of tetrapod-shaped granular artificial bones.
AB  - We have developed a novel form of granular artificial bone "Tetrabones" with a
      homogeneous tetrapod shape and uniform size. Tetrabones are four armed structures
      that accumulate to form the intergranular pores that allow invasion of cells and
      blood vessels. In this study we evaluated the physicochemical characteristics of
      Tetrabones in vitro, and compared their biological and biomechanical properties
      in vivo to those of conventional beta-tricalcium phosphate (beta-TCP) granule
      artificial bone. Both the rupture strength and elastic modulus of Tetrabone
      particles were higher than those of beta-TCP granules in vitro. The connectivity
      of intergranular pores 100, 300, and 400 MUm in size were higher in Tetrabones
      than in the beta-TCP granules. Tetrabones showed similar osteoconductivity and
      biomechanical stiffness to beta-TCP at 2 months after implantation in an in vivo
      study of canine bone defects. These results suggest that Tetrabones may be a good
      bone graft material in bone reconstruction.

PMID- 22387334
TI  - Efficiency and risk factors for CMV transmission in seronegative hematopoietic
      stem cell recipients.
AB  - Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor
      seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation
      (HCT) is surprisingly inefficient, and factors associated with transmission in
      these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R-
      HCT recipients, cumulative incidence curve estimates were used to determine
      posttransplantation rates of CMV and multivariable Cox proportional models to
      assess risk factors associated with transmission. A total of 447 patients from
      1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired
      CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before
      day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day
      100. The donor graft, specifically the total nucleated cell count (adjusted
      hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the
      only factor associated with CMV transmission in multivariable analyses. Notably,
      the source stem cells (marrow versus peripheral blood stem cell [PBSC]),
      screening method, and graft-versus-host disease (GVHD) were not associated with
      transmission. Thus, a highly cellular graft was the only identifiable risk factor
      associated with CMV transmission, suggesting that viral genomic content of the
      donor graft determines transmission efficiency in D+/R- HCT recipients.

PMID- 22387336
TI  - In vitro and in vivo studies on a Mg-Sr binary alloy system developed as a new
      kind of biodegradable metal.
AB  - Magnesium alloys have shown potential as biodegradable metallic materials for
      orthopedic applications due to their degradability, resemblance to cortical bone
      and biocompatible degradation/corrosion products. However, the fast corrosion
      rate and the potential toxicity of their alloying element limit the clinical
      application of Mg alloys. From the viewpoint of both metallurgy and
      biocompatibility, strontium (Sr) was selected to prepare hot rolled Mg-Sr binary
      alloys (with a Sr content ranging from 1 to 4 wt.%) in the present study. The
      optimal Sr content was screened with respect to the mechanical and corrosion
      properties of Mg-Sr binary alloys and the feasibility of the use of Mg-Sr alloys
      as orthopedic biodegradable metals was investigated by in vitro cell experiments
      and intramedullary implantation tests. The mechanical properties and corrosion
      rates of Mg-Sr alloys were dose dependent with respect to the added Sr content.
      The as-rolled Mg-2Sr alloy exhibited the highest strength and slowest corrosion
      rate, suggesting that the optimal Sr content was 2 wt.%. The as-rolled Mg-2Sr
      alloy showed Grade I cytotoxicity and induced higher alkaline phosphatase
      activity than the other alloys. During the 4 weeks implantation period we saw
      gradual degradation of the as-rolled Mg-2Sr alloy within a bone tunnel. Micro
      computer tomography and histological analysis showed an enhanced mineral density
      and thicker cortical bone around the experimental implants. Higher levels of Sr
      were observed in newly formed peri-implant bone compared with the control. In
      summary, this study shows that the optimal content of added Sr is 2 wt.% for
      binary Mg-Sr alloys in the rolled state and that the as-rolled Mg-2Sr alloy in
      vivo produces an acceptable host response.

PMID- 22387337
TI  - Accounting for the solubility-permeability interplay in oral formulation
      development for poor water solubility drugs: the effect of PEG-400 on
      carbamazepine absorption.
AB  - The purpose of this paper was to study the solubility-permeability interplay in
      formulation development for oral administration of poor aqueous solubility drugs.
      The apparent solubility of the lipophilic drug carbamazepine was measured in
      systems containing various levels of the co-solvent PEG-400. The corresponding
      permeability was then measured in the PAMPA assay and in the rat jejunal
      perfusion model. Thermodynamic activity was maintained equivalent in all
      permeability studies (50% saturation). PEG-400 increased carbamazepine solubility
      in a concentration-dependent fashion. Decreased carbamazepine intestinal
      permeability with increased apparent solubility was observed in both PAMPA and
      rat perfusion models. Additionally, we have shown that the intestinal absorption
      of carbamazepine is membrane-controlled, with essentially no effective barrier
      function of the unstirred water layer. A mass transport analysis was employed to
      describe the solubility-permeability interplay. It was shown that the increased
      solubility in the aqueous GI milieu reduced the apparent membrane/aqueous
      partitioning, thereby reducing the driving force for membrane permeability. The
      model enabled excellent quantitative prediction of the effective permeability as
      a function of the solubility. In conclusion, a direct tradeoff between solubility
      increase and permeability decrease has been shown, which has to be accounted for
      when developing oral formulation for lipophilic drugs.

PMID- 22387338
TI  - Alcohol, mortality and cardiovascular events in a 35 year follow-up of a
      nationwide representative cohort of 50,000 Swedish conscripts up to age 55.
AB  - AIMS: To assess the association between drinking patterns and mortality, and
      cardiovascular disease in a large cohort of young- and middle-aged men and to
      assess whether the net balance of harm and protective effect implies protective
      effect or not. METHODS: Information from health examinations, psychological
      assessments and alcohol use background in a nationally representative birth
      cohort of 49,411 male military conscripts aged 18-20 years in 1969/1970, were
      linked to mortality and hospitalization data through 2004. Cox regression
      analyses were conducted and attributable proportions (APs) calculated.
      Confounders (baseline social status, intelligence, personality and smoking) were
      taken into account. RESULTS: Increasing alcohol use was associated with
      increasing mortality (2614 deceased) and with decreasing risk for myocardial
      infarction (MI). The hazard ratio (HR) for mortality was 1.42 [95% confidence
      interval (CI) 1.10-1.82] with a consumption corresponding to 30 g 100%
      ethanol/day or more in multivariate analysis. The risk for non-fatal MI was
      significantly reduced at 60 g 100% ethanol/day (HR 0.37, 95% CI 0.15-0.90), not
      reduced for fatal MI, and non-significantly reduced for total MI. There was a
      marked association between alcohol use at conscription and mortality and
      hospitalization with alcohol-related diagnosis. APs indicate that alcohol caused
      420 deaths, 61 cases of non-fatal stroke and protected from 154 cases on non
      fatal MI. CONCLUSION: Many more deaths were caused by alcohol than cases of non
      fatal MI prevented. From a strict health perspective, we find no support for
      alcohol use in men below 55 years.

PMID- 22387339
TI  - Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma
      lipoprotein fractions.
AB  - Some cross-sectional epidemiological studies have reported positive associations
      of serum concentrations of non-high density lipoprotein cholesterol with serum
      perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). However, the
      strength of the reported associations is inconsistent for exposure-response
      across three orders of magnitude of serum PFOS and/or PFOA concentrations. These
      positive associations are unexpected based on toxicological/mechanistic studies,
      suggesting that the associations may have a biological, rather than a causal,
      basis. This study tested the hypothesis that PFOS and PFOA distribute into serum
      lipoprotein fractions such that increases in serum lipoproteins would result in
      corresponding increases in serum concentrations of PFOS and PFOA. Based on
      observed binding of PFOS and PFOA to isolated beta-lipoproteins in physiological
      saline (96% and 40% bound, respectively) in preliminary experiments using
      ultrafiltration and LC-MS/MS methods, binding to human donor plasma lipoprotein
      fractions was investigated by two density gradient methods. The majority of PFOS
      and PFOA recovered masses were found in lipoprotein-depleted plasma. Plasma
      density gradient fractionation data suggested that maximally 9% of PFOS
      distributes to lipoprotein-containing fractions, yet only 1% or less of PFOA is
      so distributed. These data do not support a strong role for plasma lipoprotein
      fractions in explaining the inconsistent dose-response associations reported in
      cross-sectional epidemiological studies.

PMID- 22387340
TI  - Detection of circulating platelet-monocyte complexes in persons infected with
      human immunodeficiency virus type-1.
AB  - Activated platelets form transient aggregates with monocytes in circulation and
      have a half-life of approximately 30-60 min. These complexes are increased in
      various inflammatory conditions and are an early marker of myocardial infarction.
      HIV-1 infection is associated with chronic inflammation, and increased CD16+
      inflammatory monocytes have been observed in these individuals, probably as a
      result of increased interaction with platelets. However, narrow detection period
      and platelet activation during sample processing pose significant problems in
      detecting platelet-monocyte complexes (PMCs). A method was standardized
      addressing these difficulties, to enumerate PMCs involving CD16+ or CD16-
      monocytes in whole blood using flow cytometry. Blood collected from healthy
      individuals was treated with either collagen (for platelet activation) or LPS
      (for monocyte activation) and subsequently used to study effect of these
      treatments on PMC formation. This method was also validated for the ex vivo
      quantitation of PMCs in blood obtained from persons infected with HIV. The in
      vitro results demonstrated that platelet activation, but not monocyte activation,
      resulted in significant increase in PMC formation. There was a significant
      increase in CD16+ PMCs and platelet activation, in samples obtained from persons
      infected with HIV as compared to those without HIV infection. Furthermore, PMC
      percentages correlated positively with platelet activation. These findings
      improve the ability to detect PMCs and shed light on HIV pathogenesis.

PMID- 22387341
TI  - A multiplex RT-PCR assay for detection and differentiation of avian H3, H5, and
      H9 subtype influenza viruses and Newcastle disease viruses.
AB  - Avian influenza viruses (AIVs) and Newcastle disease viruses (NDVs) co-circulate
      in the poultry population in China. These viruses cause repeated disease
      outbreaks that exhibit similar clinical symptoms and epidemiological patterns. H5
      and H9 influenza viruses are the major pathogens infecting poultry stocks.
      Recently, H3 AIV (one of the main subtypes in waterfowl) has become endemic in
      chickens. A multiplex reverse-transcriptase polymerase chain reaction (mRT-PCR)
      assay was designed for simultaneous detection and differentiation of avian H3,
      H5, H9 subtype AIVs and NDVs. Four primer sets were evaluated, three of which
      specifically targeted the hemagglutinin genes of H3, H5 and H9 AIVs, while the
      other targeted the NDV fusion gene. The sensitivity and specificity of the mRT
      PCR assay was determined. The assay detected the major clades or genotypes of all
      of the reference AIVs and NDVs currently circulating in China. In addition, the
      mRT-PCR results obtained from screening 380 clinical swabs and 12 experimental
      tracheal samples were consistent with those obtained using conventional virus
      isolation methods. The mRT-PCR assay was established successfully for the
      detection and differentiation of avian H3, H5, and H9 subtype AIVs and NDVs. The
      method should, therefore, provide a valuable diagnostic tool for these
      infections.

PMID- 22387342
TI  - High transformation efficiency of Bacillus subtilis with integrative DNA using
      glycine betaine as osmoprotectant.
AB  - Electroporation is an important approach for genetic engineering experiments
      allowing for introduction of foreign DNA in a selected host. Here, we describe
      for the first time the use of glycine betaine as an osmoprotectant for
      electroporation of gram-positive bacteria Bacillus subtilis. High electroporation
      efficiency (up to 5*10(5) cfu/MUg) was obtained using 7.5% glycine betaine. The
      new method improved the transformation efficiency of B. subtilis with linear
      integrative DNA nearly 700-fold compared with existing Bacillus transformation
      techniques.

PMID- 22387343
TI  - Single-cell level analysis of megakaryocyte growth and development.
AB  - Several fundamental questions regarding cell growth and development can be
      answered by recording and analyzing the history of cells and their progeny.
      Herein, long-term and large-field live cell imaging was used to study the process
      of megakaryopoiesis at the single cell level (n = 9300) from human CD34+ cord
      blood (CB) in the presence of thrombopoietin (TPO) or the cytokine cocktail BS1
      with or without nicotinamide (NIC). Comparative analyses revealed that the
      cocktail BS1 increased the mitotic and proplatelet rate of diploid and polyploid
      cells, respectively. Conversely, only NIC treatment increased the endomitotic
      rate of megakaryocytes (MKs) leading to the formation of CB-MKs with ploidy level
      frequently observed with BM-MKs. However, NIC failed to enhance platelet
      production. Rather, a 7- and 31-fold reduction in proplatelet formation was
      observed in tetraploid and octaploid CB-MKs, respectively, and ex vivo platelet
      production output was reduced by half due to a reduction in MK output in NIC
      cultures. Unexpectedly, a significant fraction of di- and polyploid CB-MKs were
      seen to undergo complete proplatelet regression. Though rare (< 0.6%),
      proplatelet reversal led to the formation of regular round cells that could at
      times resume normal development. The cell tracking data was then used to
      investigate the impact of "developmental fate" and ploidy on cell cycling time,
      and to identify potential developmental patterns. These analyses revealed that
      cell fate and ploidy level have major impacts on the cell cycling time of the
      cells, and that four recurrent cell lineage patterns could be identified for
      CD34+ cells undergoing MK differentiation.

PMID- 22387344
TI  - TAK1 promotes BMP4/Smad1 signaling via inhibition of erk MAPK: a new link in the
      FGF/BMP regulatory network.
AB  - FGFs and BMPs act in concert to regulate a wide range of processes in vertebrate
      development. In most cases, FGFs and BMPs have opposing effects, and specific
      developmental outcomes arise out of a balance between the two growth factors. We
      and others have previously demonstrated that signaling pathways activated by FGFs
      and BMPs interact via inhibitory crosstalk. Here we demonstrate a role for the
      BMP effector TGF-beta Activated Kinase 1 (TAK1) in the maintenance of Smad1
      activity in Xenopus embryos, via the inhibition of erk MAPK. Up- or
      downregulation of TAK1 levels produces an inverse alteration in the amount of
      activated erk MAPK. The inhibition of erk MAPK by TAK1 is mediated by p38 and a
      corresponding decrease in phosphorylation of MEK. TAK1 morphant embryos show a
      decrease in the nuclear accumulation of Smad1. Conversely, reduction of erk MAPK
      activity via overexpression of MAP Kinase Phosphatase1 (MKP1) leads to an
      increase in nuclear Smad1. Both TAK1 morphant ectoderm and ectoderm treated with
      FGF show a decrease in the expression of several Smad1-inducible genes. Neural
      specific gene expression is inhibited in isolated ectoderm coexpressing noggin
      and TAK1, suggesting that TAK1 is sufficient to inhibit neural specification.
      Introduction of TAK1 morpholino oligonucleotide expands the expression of
      organizer genes, disrupts formation of the boundary between organizer and non
      organizer mesoderm, and increases the spatial range of MAPK activation in
      response to localized FGF. Our results indicate that inhibitory interactions
      between FGF and BMP4 effector pathways increase the robustness of BMP signaling
      via a feed-forward mechanism.

PMID- 22387345
TI  - An insecticidal protein from Xenorhabdus budapestensis that results in
      prophenoloxidase activation in the wax moth, Galleria mellonella.
AB  - Xenorhabdus budapestensis can produce a variety of proteins that help this
      bacterium and its mutualistic nematode vector kill the host insect. In this
      report, we purified one protein fraction from the intracellular extract of X.
      budapestensis D43, which was designated HIP57. By injection, HIP57 caused
      Galleria mellonella larval bodies to blacken and die with an LD(50) of 206.81
      ng/larva. Analyzes of HIP57 by two-dimensional gel electrophoresis showed that
      this protein was a single spot on the gel with a molecular weight of 57 kDa and a
      pI of ~5. Sequencing and bioinformatic analysis suggested that the HIP57 toxin
      was homologous to GroEL. GroEL has been accepted as molecule chaperon; however,
      our research revealed that HIP57 (GroEL) possesses another novel function as an
      insecticide. A GroEL phylogenetic tree defined the relationship among the related
      species of mutualistic bacteria (Xenorhabdus and Photorhabdus) from the
      entomopathogenic nematodes and the evolution within the family
      Enterobacteriaceae. Thus, GroEL could be a complement to 16S rDNA for studying
      the molecular phylogenies of the family Enterobacteriaceae. Phenoloxidase (PO)
      activity analysis of G. mellonella larvae injected with HIP57 suggested that the
      toxin activates the PO cascade, which provides an extensive defense reaction that
      potentially responsible for G. mellonella larval death.

PMID- 22387346
TI  - Characterization of ion profiles in light-emitting electrochemical cells by
      secondary ion mass spectrometry.
AB  - Ion profiles in polymer light-emitting electrochemical cells are known to
      significantly affect performance and stability, but are not easily measured.
      Here, secondary ion mass spectrometry is used to investigate ion profiles in both
      dynamic and chemically fixed junction devices. Results indicate lower
      reversibility of dynamic junctions and a more significant time delay for ion
      redistribution than previously expected, but confirm the complete immobilization
      of ions in chemically fixed junction devices. When compared with prior studies
      analyzing the electric field profiles in similar devices, these results help to
      elucidate the roles of ion distribution and electrochemical doping in LECs.

PMID- 22387347
TI  - Clostridium difficile infection after allogeneic hematopoietic stem cell
      transplantation: incidence, risk factors, and outcome.
AB  - Clostridium difficile (C. difficile) infection was observed in 13% of recipients
      after hematopoietic stem cell transplantation (HSCT), mainly in the first month
      posttransplantation. Risk factors were cord blood as the source of stem cells,
      acute graft-versus-host disease (GVHD), and total body irradiation (TBI). No
      association was found with an increased risk of mortality. The purpose of this
      study was to evaluate the incidence, risk factors, and outcome of C. difficile
      infection (CDI) after HSCT. We conducted a single-center, retrospective, cohort
      study on all patients who received an allogeneic HSCT from January 2004 to
      December 2007. All patients with diarrhea in the first year after HSCT were
      tested for the presence of C. difficile in stools. Among the 407 assessable
      patients, 53 presented at least 1 CDI in the first year post-HSCT. The total
      incidence rate was 5.6 cases of CDI per 10,000 patient-days. Fifty percent of
      cases were diagnosed in the first month after HSCT, and 95% occurred during the
      first 6 months. Fewer than 5% of patients with CDI had severe diarrhea and severe
      complications were never observed. TBI in the conditioning regimen, cord blood as
      the source of stem cells, and acute graft-versus-host disease (aGVHD) were
      independently associated with CDI. Six patients (11%) had a recurrence of CDI.
      Four patients required second-line treatment with vancomycin. With a median
      follow-up of 22 months, the 2-year overall survival rates were similar between
      patients who presented a CDI and those who did not. CDI was observed in
      approximately 13% of recipients after HSCT, mainly in the first month
      posttransplantation and was associated with CB, aGVHD, and TBI. CDI was not
      associated either with severe complications or with an increased risk of
      mortality in this large cohort of patients.

PMID- 22387348
TI  - A prognostic index for survival among mechanically ventilated hematopoietic cell
      transplant recipients.
AB  - The prognosis of recipients of allogeneic hematopoietic cell transplantation
      (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883
      adults undergoing allogeneic HCT at the University of Minnesota between 1998 and
      2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the
      outcomes of these patients to develop a prognostic index to predict the 100-day
      post-MV overall survival (OS) based on factors present at the time of MV. The 179
      patients were divided at random into a training set (n = 119) and a validation
      set (n = 60). The 100-day postventilation OS was 17% for the total population.
      Multivariate Cox regression on the training set identified creatinine <2 mg/dL
      and platelet count >20 * 10(9)/L as significant predictors of better OS.
      Recursive partitioning classified patients with these good prognostic criteria
      into class A (n = 76); all other patients were classified as class B (n = 103).
      Among class A patients, 100-day OS was 29% in the training set and 30% in the
      validation set. Corresponding OS in class B patients was 5% and 15%,
      respectively. This prognostic index should help guide physicians in counseling
      HCT patients and their families regarding the use of MV and potential outcomes.

PMID- 22387349
TI  - HLA-matched sibling transplantation for severe aplastic anemia: impact of HLA
      DR15 antigen status on engraftment, graft-versus-host disease, and overall
      survival.
AB  - The HLA class II DRB1 antigen DR15 (common alleles *1501, *1502) is an important
      marker in the pathobiology of severe aplastic anemia (SAA). We studied 1204
      recipients of HLA-matched sibling bone marrow transplantation for SAA to
      determine whether HLA DR15 status (as determined by allele-level typing) affected
      hematopoietic recovery, graft-versus-host disease (GVHD), or overall survival
      (OS). In multivariate analysis, secondary graft failure rate at 2 years was lower
      in patients who were HLA DR15+ (hazard ratio = 0.46, P = .01). However,
      neutrophil recovery at day -28, platelet recovery at day -100, acute GVHD,
      chronic GVHD, and overall mortality were independent of DR15 status. The 5-year
      probabilities of OS, after adjusting for age, race, performance score, transplant
      conditioning regimen, and year of transplantation, were 78% and 81% for patients
      who were HLA DR15+ and HLA DR15-, respectively (P = .35). In conclusion, DR15
      status is associated with secondary graft failure after HLA-matched sibling bone
      marrow transplantation for SAA but has no significant impact on survival.

PMID- 22387350
TI  - Acute toxicity of chlorobenzenes in tetrahymena: estimated by microcalorimetry
      and mechanism.
AB  - The toxicity of chlorobenzenes to Tetrahymena growth metabolism was studied by
      microcalorimetry. The growth constant (k), peak time (T) and generation times
      (T(G)) were calculated. IC(50) of chlorobenzenes was obtained through the kinetic
      parameters. The results suggested that the order of toxicity was 1,2,4
      trichlorobenzene>o-dichlorobenzene>p-dichlorobenzene>m
      dichlorobenzene>chlorobenzene. ATR-FTIR spectra revealed that amide groups and
      PO(2)(-) of the phospholipid phospho-diester, both in the hydrophobic end exposed
      to the outer layer, were the easiest to be damaged. The relationship between
      IC(50) and chemicals structure parameters (E(LUMO), E(HOMO), logK(OW), ?Q(R),
      DeltaQ(piR) and DeltaE), indicated that the more chlorine atoms were substituted,
      the greater the toxicity was. Chlorobenzenes have toxicity of non-polar narcosis.
      Their toxicity is proportional to their concentrations at the site of action, and
      caused by membrane perturbation.

PMID- 22387351
TI  - The impact of Triton WR-1339 induced hyperlipidemia on the effects of
      benzo(a)pyrene or guaiacol on alpha- and gamma-tocopherol pools and selected
      markers of pro-/antioxidative balance in rat plasma and erythrocytes.
AB  - The toxicity of carcinogenic benzo(a)pyrene (BaP) can be intensified by the pro
      oxidative effects of metabolic activation. The oxidatively active products can be
      formed during enzymatic biotransformation or in the process of co-oxygenation
      with lipid peroxidation. This study assesses if the acute hyperlipidemia can
      increase pro-oxidative effects of BaP as a factor intensifying processes of lipid
      peroxidation and co-oxygenation. After three days of i.p. administration of BaP
      or guaiacol (equimolar dose 10mg/kg b.w.) without or with the hyperlipidemia
      inducer-Triton WR-1339 to male Wistar rats, the levels of alpha- and gamma
      tocopherol were measured in erythrocytes and plasma together with the level of
      lipid peroxidation as malonyldialdehyde (MDA) concentration. Guaiacol was chosen
      as a reference substance due to its high ability to co-oxygenate. Additionally,
      the activity of superoxide dismutase (Cu,ZnSOD) in erythrocytes and plasma was
      monitored. In normolipaemic groups the significant decrease in erythrocyte alpha
      tocopherol pool and the increase in lipid peroxidation level were observed after
      BaP or guaiacol administration. In hyperlipaemic groups, despite the increase in
      the level of lipid peroxidation, there were no additional effects in tocopherol
      pools compared to the normolipaemic groups which could be attributed to co
      oxygenation. Decrease of alpha-tocopherol in erythrocytes was proportional to the
      reduction in normolipemic subjects when accounting for the migration to
      hyperlipemic plasma. There was no co-oxygenation effect on the activity of
      superoxide dismutase (Cu,ZnSOD) in blood.

PMID- 22387353
TI  - Study on cytotoxicity and structure-activity relationship of HL-7702 cell exposed
      to naphthoquinones.
AB  - The acute cytotoxicities of six naphthoquinone compounds, including Atovaquone,
      Buparvaquone, Menadione, 2-acetoxy-1,4-naphthoquinone and 2-ethoxy-1,4
      naphthoquinone, to HL-7702 cells were determined. The results showed that the
      toxicities of these naphthoquinones were characterized by a steep response
      pattern except for 2-hydroxy-1,4-naphthoquinone. Meanwhile, the cellular injuries
      were unrecoverable. Several molecular descriptors, such as the octanol-water
      partition coefficients (LogP), diameter (Dia) and topological index (TIndx),
      played an important role in the toxicity of naphthoquinones to HL-7702 cell. Our
      results provide a foundation for further investigation using 3D-QSAR and HQSAR to
      evaluate the aquatic ecological risk and the possible mechanisms of toxicity of
      naphthoquinones.

PMID- 22387352
TI  - Alterations in differentially expressed genes by exposure to a mixture of
      carcinogenic polycyclic aromatic hydrocarbons in the liver of Oryzias latipes.
AB  - The effects of a mixture of carcinogenic polycyclic aromatic hydrocarbons (cPAHs)
      on transcriptional responses in the liver of medaka, Oryzias latipes, were
      investigated by identifying differentially expressed genes (DEGs). Five DEGs were
      identified as cytochrome P450 2P1 (CYP450 2P1), malate dehydrogenase, anti
      thrombin III, NADH dehydrogenase subunit 4, and transferrin. These DEGs were
      quantified by real-time polymerase chain reaction. Only CYP450 2P1 mRNA was found
      to be upregulated by exposure to cPAHs mixture, suggesting that CYP450 2P1 mRNA
      can be a potential marker for prediction of the biological effects of a mixture
      of cPAHs on fish.

PMID- 22387354
TI  - Mono-2-ethylhexyl phthalate induced loss of mitochondrial membrane potential and
      activation of Caspase3 in HepG2 cells.
AB  - L02 and HepG2 cells were exposed to mono-(2-ethylhexyl) phthalate (MEHP) at
      concentrations of 6.25-100MUM. After 48h treatment, MEHP decreased HepG2 cell
      viability in a concentration-dependent manner and L02 cell viability in the 50
      and 100MUM groups (p<0.01). Furthermore, at 24 and 48h after treatment, MEHP
      decreased the glutathione levels of HepG2 cells in all treatment groups and in
      the DeltaPsi(m) in L02 and HepG2 cells with MEHP>=25MUM (p<0.05 or p<0.01). At
      24h after treatment, MEHP induced activation of caspase3 in all treated HepG2 and
      L02 cells (p<0.05 or p<0.01) except the 100MUM MEHP treatment group. The increase
      in the Bax to Bcl-2 ratio suggests that Bcl-2 family involved in the control of
      MEHP-induced apoptosis in these two cell types. The data suggest that MEHP could
      induce apoptosis of HepG2 cells through mitochondria- and caspase3-dependent
      pathways.

PMID- 22387355
TI  - Evaluation of spatial and temporal changes in biomarker responses in the common
      carp (Cyprinus carpio L.) for biomonitoring the Meric Delta, Turkey.
AB  - The aim of this study is to examine the activity of several biomarkers in carp,
      Cyprinus carpio L., to determine their response to xenobiotics, such as
      organochlorine pesticides (OCPs), in the Meric Delta. Fish were collected from
      contaminated sites and from areas regarded as relatively less contaminated in
      four sampling periods. Hepatic glutathione S-transferase (GST), carboxylesterase
      (CaE), lactate dehydrogenase, aspartate aminotransferase, and acid phosphatase
      activities were measured as biomarkers in the fish. For all fish, the condition
      factor and hepatosomatic index, were calculated to determine the condition of the
      fish. The results of this study indicated that the mean GST activity showed an
      increase in fish from the Meric-Ergene junction site and a decrease in Enez site
      with respect to fish from Meric site. Furthermore, the study shows that spatial
      and temporal changes of biomarkers such as GST and CaE might be useful for the
      assessment of environmental contamination in the Meric Delta.

PMID- 22387357
TI  - From the editor.

PMID- 22387356
TI  - Capillary electrophoresis and small molecule drug discovery: a perfect match?
AB  - Capillary electrophoresis (CE) is an analytical technique based on the separation
      of the analytes within a capillary owing to their different electrophoretic
      mobilities. It is widely used in pharmaceutical analyses owing to its versatility
      and high separation power. However, its penetration into the drug discovery scene
      has been relatively limited until recent years. Several factors have contributed
      to this low implementation, including the maturity of liquid chromatography, the
      scarcity of experienced CE practitioners, and certain limitations intrinsic to
      the technique. Recently, instrumental improvements and the growing demand for
      analytical information have lead to a continuously expanding range of routine
      electrophoretic applications throughout pharmaceutical discovery and development.
      In this article we review CE fundamentals, review well-established CE
      methodologies in drug discovery of small molecules and discuss trends that, in
      our opinion, might emerge in the coming years.

PMID- 22387358
TI  - Botulinum toxin type B: An effective treatment for alleviating pain associated
      with cervical dystonia.
AB  - Neck pain is reported in 75% is strongly associated with greater disability and
      decreased quality of life. Botulinum toxin type B (BoNT-B; Myobloc?) is a new
      botulinum toxin that has been proven safe and effective in reducing the pain,
      severity, and disability of patients with cervical dystonia. We analyzed a subset
      of efficacy data from two randomized, double blind, placebo-controlled clinical
      trials. The first study consisted of three treatment groups in patients who were
      responders to the type A toxin, including placebo (<FORMULA>n=36</FORMULA>), 5000
      units (U) (<FORMULA>n=36</FORMULA>), 10,000 U (<FORMULA>n=37</FORMULA>). The
      second study consisted of placebo (n=38) and 10,000-U treatment groups
      (<FORMULA>n=39</FORMULA>) in patients not responding to the type A toxin. For
      this analysis, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
      subscale scores for pain and three visual analog scales (Patient Analog Pain,
      Patient Global, and Principal Investigator Global Assessments) were evaluated. A
      dose-response effect was observed in the reduction of pain based on the TWSTRS
      subscale scores. In both studies, mean improvements from baseline to week 4 for
      all patients were significant compared with placebo (<FORMULA>P<0.005</FORMULA>).
      BoNT-B also significantly improved mean values for all VAS assessments. Our
      analysis confirms that BoNT-B significantly reduces the pain associated with
      cervical dystonia and improves patients' overall condition. This clinical benefit
      suggests that BoNT-B may be useful in other pain syndromes involving involuntary
      muscle spasms or contractions.

PMID- 22387359
TI  - Comparison of two different techniques of electrotherapy on myofascial pain.
AB  - This study was designed to compare the effects of Transcutaneus Electrical Nerve
      Stimulation (TENS) and Electrical Muscle Stimulation (EMS) on myofascial trigger
      point (MTrP) of the upper trapezius muscle. A total of 40 patients were randomly
      divided into three groups. All patients had active MTrP in one side of the upper
      trapezius muscles. Group I was treated with TENS and trapezius-stretching
      exercises; Group II was treated with EMS and trapezius-stretching exercises and
      Group III, the control group, had only trapezius-stretching exercises. Subjective
      pain intensity with VAS, range of motion (ROM), and pain threshold (PT) were
      assessed before, immediately after two week treatment and 3 months after
      treatment. Group I had a statistically significant reduction in VAS
      (<FORMULA>P<0.01</FORMULA>), increase in PT and ROM (<FORMULA>p<0.05</FORMULA>)
      at end of the treatment when compared with the control group. Only VAS was
      significantly improved (<FORMULA>p<0.05</FORMULA>) in the Group II patients. At
      the end of the third month, both groups showed highly significant improvement
      (<FORMULA>p<0.01</FORMULA>) in VAS and PT (but not ROM). There was no statistical
      difference in none of parameters between EMS and TENS groups in any time
      (<FORMULA>p>0.05</FORMULA>). In conclusion, TENS seem to be more effective
      immediately after treatment but in long term evaluation there is no significant
      superiority of two electrotherapy techniques on each other.

PMID- 22387360
TI  - Back extensor muscle fatigability in chronic low back pain patients and controls:
      Relationship between electromyogram power spectrum changes and body mass index.
AB  - Back extensor muscle fatigability and its relationship to body mass index (BMI)
      was measured in 12 chronic nonspecific low back pain (CNLBP) patients (7 women
      and 5 men) and 12 healthy age-and gender-matched controls. Subjects performed
      Sorensen back isometric endurance test until exhaustion while EMG spectral mean
      power frequency (MPF) over the lumbar erector spinae muscle and endurance time
      were recorded. The CNLBP patients had significantly shorter endurance time than
      healthy controls. Spectral MPF significantly declined as time of isometric
      contraction progressed. Relative decrease of the MPF per minute (MPF slope) for
      left and right side, and pooled MPF slope was significantly higher in CNLBP
      patients compared with controls. In CNLBP patients the isometric endurance time
      correlated significantly negatively with BMI (<FORMULA>r=-0.71</FORMULA>). In
      controls BMI correlated significantly positively with MPF slopes of left
      (<FORMULA>r=0.68</FORMULA>) and right (<FORMULA>r=0.57</FORMULA>) side, and
      pooled MPF slope (<FORMULA>r=0.62</FORMULA>).

PMID- 22387361
TI  - Development of lumbar extension strength: Effect of pelvic stabilization during
      resistance training.
AB  - The purpose of this studywas to determine the effect of pelvic stabilization
      during resistance training on the development of isometric lumbar extension
      strength (torque output) when testing and training are conducted on a lumbar
      dynamometer. Eighteen healthy volunteers were randomly assigned to one of two
      groups that trained on a lumbar extension dynamometer: One trained with pelvic
      stabilization (n = 9) and the other trained without pelvic stabilization (n = 9).
      Peak isometric lumbar extension torque was measured on the dynamometer at seven
      angles over the full range of lumbar flexion, before and after a twelve-week, one
      time per week dynamic progressive resistance exercise program. Following
      training, peak isometric torque increased for the stabilization and without
      stabilization groups (average increase of 15.8 +/- 11.8% and 20.6 &plusmn ;17.2%,
      respectively; p <= 0.05), while there was no difference in torque production
      between the groups (p > 0.05). This study demonstrates that pelvic stabilization
      is not required during training to develop lumbar extension strength when testing
      and training are conducted on the same machine.

PMID- 22387362
TI  - Nicotine and caffeine intake in complex regional pain syndrome.
AB  - {?it OBJECTIVE: } Nicotine and caffeine are vasoconstrictors. Complex regional
      pain syndrome (CRPS) is defined to involve disproportionate pain and autonomic
      dysfunction [1]. The objectives of this study were to identify the prevalence of
      smoking and caffeine intake in CRPS, to explore the relationship of pain
      intensity with smoking and caffeine consumption, and to explore the relationship
      of pain intensity, anxiety and disability among CRPS patients who smoke, use
      caffeine, or both.  {?it DESIGN: } One hundred eleven patients, with CRPS type I
      or II, from two academic rehabilitation pain clinics were reviewed. Data were
      collected retrospectively by reviewing CRPS patients' self-reported pain level
      using visual analogue scales (VAS), Beck Depression Inventory (BDI), Pain
      Disability Index (PDI), and Pain Anxiety Symptoms Scale (PASS). Status of daily
      smoking and caffeine consumption were also recorded.  {?it RESULTS: } Smoking
      prevalence among CRPS was significant higher than the national average (p <
      0.001). There were no significant relationships between the perceived pain level
      and either daily smoking, daily caffeine intake, or both (p > 0.430). In patients
      with CRPS I higher PASS scores were positively associated with dichotomous use of
      smoking and caffeine (p < 0.05). The PASS scores among patients with CRPS~II were
      not available for analysis.  {?it CONCLUSIONS: } The smoking prevalence was
      higher than the national average among patients with CRPS I and II. Among
      patients with CRPS~I smoking and caffeine consumption were greater in those who
      reported more pain-related anxiety, but did not influence pain intensity. The
      clinical implications of these findings will be discussed.

PMID- 22387363
TI  - Whiplash associated disorders -- subjective complaints vs clinical and objective
      findings. A retrospective study of 866 patients.
AB  - The subjective complaints of 866 WAD (whiplash associated disorders) patients
      were recorded at a follow-up examination some 32 months after the accident. The
      complaints were compared to a number of relatively objective examinations -- X
      ray, CT, MRI, EMG, Bone scan, and clinical assessment. Neck pain and radiating
      pain to the limbs were the major complaints. The big majority of the X-rays
      findings, both primary and late (98%), were found either non-pathological or
      indicating degenerative changes and old fractures. All positive CT and MRI
      findings not related to known degenerative changes and old fractures were
      considered relevant. Bone-scan and clinical findings not related to old injuries
      were considered to be relevant to the WAD. Positive EMG findings were considered
      relevant except for those related with incidental CTS. Comparing the various
      testing modalities, CT and EMG were found positive in 25% and 33% of the tested
      sample (11% and 12% of the whole WAD patients), accordingly. Bone-scan and MRI
      were conducted in a much smaller sample of the patients, and only 33% and 25% (3%
      and 2% of the whole population) were found pathologic, accordingly. Clinically, C
      C (chin-chest touch) and RoM tests identified 75 (9%) and 58 (7%) of the
      pathologic population, accordingly. Excluding degenerative changes and incidental
      CTS, only 25% of the patients had any objective supporting findings.

PMID- 22387364
TI  - Case report and rehabilitative management of a complete musculocutaneous nerve
      injury caused by shoulder dislocation.
AB  - Anterior shoulder dislocation can secondarily cause nerve injury and/or rotator
      cuff tear. An elderly male with a recent shoulder dislocation and multiple
      medical comorbidities was transferred to a rehabilitation inpatient service in
      order to maximize his functional status. Physical exam suggested a brachial
      plexus injury. Electrodiagnostic testing confirmed a complete musculocutaneous
      and a partial axillary nerve lesion. This specific combination of nerve lesions
      is a previously unreported complication of anterior shoulder dislocation.
      Prognosis and treatment are discussed, particularly the use of electrodiagnostic
      findings to tailor rehabilitation program design.

PMID- 22387365
TI  - Fine mapping analysis of a region of 20q13.33 identified five independent
      susceptibility loci for glioma in a Chinese Han population.
AB  - Genome-wide association studies have identified the susceptibility single
      nucleotide polymorphisms (SNPs) of glioma at chromosome 20q13.33, and the
      replication study conducted among Chinese Han population also confirmed the
      susceptibility locus rs6010620 is located in this region. To identify other
      genetic variants in 20q13.33, we genotyped 13 common tagging SNPs and imputed 86
      additional SNPs in a region ~100 kb at 20q13.33 among 1027 controls and 987
      cases. Among 99 SNPs, five independent susceptibility loci (20-62315594 in RTEL1,
      20-62335293 in adenosine diphosphate ribosylation factor-related protein 1,
      rs3761121 in ZGPAT, rs1058319 in SLC2A4RG and rs5019252 in ZBTB46) were
      identified for glioma. Two of the five SNPs (20-62335293, P = 3.09 * 10(-10) and
      rs1058319, P = 1.26 * 10(-11)) satisfied the threshold of genome-wide
      significance (P < 10(-8)). Further stratified analysis revealed that 20-62315594
      was only significantly associated with glioblastoma (GBM) risk [P = 1.71 * 10(-8)
      for trend test, adjusted odds ratio (OR) = 1.99, 95% confidence interval (CI) =
      1.57-2.52]. Other four SNPs were significantly associated with both GBM and
      astrocytoma. The risk of glioma increased with the increase of the number of risk
      alleles (P = 1.94 * 10(-11), for trend test, adjusted OR = 1.43, 95% CI = 1.29
      1.58), and the individuals who carried 7-10 risk alleles had a 2.64-fold
      increased risk of glioma development compared with those who carried 0 risk
      allele (P = 8.71 * 10(-7), adjusted OR = 2.64, 95% CI = 1.79-3.88). Our results
      indicated a complex effect contributing to glioma risk at 20q13.33, which may
      provide a new insight into glioma development. Both variants and genes in this
      region should be considered in future studies designed to investigate the
      biological functions.

PMID- 22387366
TI  - CLIC4 is a tumor suppressor for cutaneous squamous cell cancer.
AB  - Chloride intracellular channel (CLIC) 4 is a member of a redox-regulated,
      metamorphic multifunctional protein family, first characterized as intracellular
      chloride channels. Current knowledge indicates that CLICs participate in
      signaling, cytoskeleton integrity and differentiation functions of multiple
      tissues. In metabolically stressed skin keratinocytes, cytoplasmic CLIC4 is S
      nitrosylated and translocates to the nucleus where it enhances transforming
      growth factor-beta (TGF-beta) signaling by protecting phospho-Smad 2 and 3 from
      dephosphorylation. CLIC4 expression is diminished in multiple human epithelial
      cancers, and the protein is excluded from the nucleus. We now show that CLIC4
      expression is reduced in chemically induced mouse skin papillomas, mouse and
      human squamous carcinomas and squamous cancer cell lines, and the protein is
      excluded from the nucleus. The extent of reduction in CLIC4 coincides with
      progression of squamous tumors from benign to malignant. Inhibiting antioxidant
      defense in tumor cells increases S-nitrosylation and nuclear translocation of
      CLIC4. Adenoviral-mediated reconstitution of nuclear CLIC4 in squamous cancer
      cells enhances TGF-beta-dependent transcriptional activity and inhibits growth.
      Adenoviral targeting of CLIC4 to the nucleus of tumor cells in orthografts
      inhibits tumor growth, whereas elevation of CLIC4 in transgenic epidermis reduces
      de novo chemically induced skin tumor formation. In parallel, overexpression of
      exogenous CLIC4 in squamous tumor orthografts suppresses tumor growth and
      enhances TGF-beta signaling. These results indicate that CLIC4 suppresses the
      growth of squamous cancers, that reduced CLIC4 expression and nuclear residence
      detected in cancer cells is associated with the altered redox state of tumor
      cells and the absence of detectable nuclear CLIC4 in cancers contributes to TGF
      beta resistance and enhances tumor development.

PMID- 22387367
TI  - The G protein beta subunit controls virulence and multiple growth- and
      development-related traits in Verticillium dahliae.
AB  - To gain insight into the role of G protein-mediated signaling in virulence and
      development of the soilborne, wilt causing fungus Verticillium dahliae, the G
      protein beta subunit gene (named as VGB) was disrupted in tomato race 1 strain of
      V. dahliae. A resulting mutant strain, 70DeltaGb15, displayed drastic reduction
      in virulence, increased microsclerotia formation and conidiation, and decreased
      ethylene production compared to the corresponding wild type (wt) strain 70wt-r1.
      Moreover, 70DeltaGb15 exhibited an elongated rather than radial growth pattern on
      agar media. A transformant of 70DeltaGb15 (named as 70DeltaGbPKAC1) that carries
      an extra copy of VdPKAC1, a V. dahliae gene encoding the catalytic subunit of the
      cAMP-dependent protein kinase A, exhibited wt growth pattern and conidiation, was
      unable to form microsclerotia, produced high amounts of ethylene, and exhibited
      virulence between that of 70DeltaGb15 and 70wt-r1 on tomato plants. Phenotypical
      changes observed in 70DeltaGb15 and 70DeltaGbPKAC1 correlated with
      transcriptional changes in several genes involved in signaling (MAP kinase VMK1)
      and development (hydrophobin VDH1 and ACC synthase ACS1) of V. dahliae. Results
      from the present work suggest a linkage between VGB and VdPKAC1 signaling
      pathways in regulating virulence, hormone production and development in V.
      dahliae.

PMID- 22387369
TI  - Design of a long-term antipsychotic in situ forming implant and its release
      control method and mechanism.
AB  - Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics,
      risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide
      co-glycolide)(PLGA) as carrier, were investigated. Significant difference was
      observed in the solution-gel transition mechanism of the two systems: homogeneous
      system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and
      heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was
      dispersed. Fast solvent extractions were found in both systems, but in comparison
      with the high drug release rate from homogeneous system of drug/polymer/NMP, a
      fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was
      not accompanied by a high drug release rate but a rapid solidification of the
      implant, which resulted in a high drug retention, well-controlled initial burst
      and slow release of the drug. In vivo study on beagle dogs showed a more than 3
      week sustained release with limited initial burst. Pharmacologic evaluation on
      optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day
      to 38 day on the MK-801 induced schizophrenic behavior mice model. A long
      sustained-release antipsychotic ISFI of 50% drug loading and controlled burst
      release was achieved, which indicated a good potential in clinic application.

PMID- 22387370
TI  - Passive and iontophoretic transdermal delivery of phenobarbital: Implications in
      paediatric therapy.
AB  - The objective of this investigation was to evaluate phenobarbital transdermal
      delivery for possible use in paediatric care. In vitro experiments were performed
      using intact pig skin and barriers from which the stratum corneum had been
      stripped to different extents to model the less resistant skin of premature
      babies. Cathodal iontophoretic delivery of phenobarbital was superior to anodal
      transport and optimised delivery conditions were achieved by reduction of
      competing co-ion presence in the drug formulation. Phenobarbital transport across
      intact or partially compromised skin was controlled by iontophoresis which was
      more efficient than passive diffusion. Across highly compromised skin, however,
      passive diffusion increased drastically and iontophoretic control was lost.
      Overall, this study demonstrates the feasibility of phenobarbital transdermal
      delivery for paediatric patients.

PMID- 22387368
TI  - Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and
      Parkinson's disease.
AB  - Cognitive dysfunction is one of the most typical characteristics in various
      neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease
      (advanced stage). Although several mechanisms like neuronal apoptosis and
      inflammatory responses have been recognized to be involved in the pathogenesis of
      cognitive dysfunction in these diseases, recent studies on neurodegeneration and
      cognitive dysfunction have demonstrated a significant impact of receptor
      modulation on cognitive changes. The pathological alterations in various
      receptors appear to contribute to cognitive impairment and/or deterioration with
      correlation to diversified mechanisms. This article recapitulates the present
      understandings and concepts underlying the modulation of different receptors in
      human beings and various experimental models of Alzheimer's disease and
      Parkinson's disease as well as a conceptual update on the underlying mechanisms.
      Specific roles of serotonin, adrenaline, acetylcholine, dopamine receptors, and N
      methyl-D-aspartate receptors in Alzheimer's disease and Parkinson's disease will
      be interactively discussed. Complex mechanisms involved in their signaling
      pathways in the cognitive dysfunction associated with the neurodegenerative
      diseases will also be addressed. Substantial evidence has suggested that those
      receptors are crucial neuroregulators contributing to cognitive pathology and
      complicated correlations exist between those receptors and the expression of
      cognitive capacities. The pathological alterations in the receptors would,
      therefore, contribute to cognitive impairments and/or deterioration in
      Alzheimer's disease and Parkinson's disease. Future research may shed light on
      new clues for the treatment of cognitive dysfunction in neurodegenerative
      diseases by targeting specific alterations in these receptors and their signal
      transduction pathways in the frontal-striatal, fronto-striato-thalamic, and
      mesolimbic circuitries.

PMID- 22387371
TI  - Response to the Center for Medicare & Medicaid Services coverage with evidence
      development request for primary prevention implantable cardioverter
      defibrillators: data from the OMNI study.
AB  - BACKGROUND: The Center for Medicare & Medicaid Services expanded coverage for
      primary prevention (PP) implantable cardioverter-defibrillators (ICDs) included a
      request for outcome comparisons between 3 Group B subgroup patients (left
      ventricular ejection fraction [LVEF] 31%-35%, nonischemic dilated cardiomyopathy
      [NDCM] duration of <9 months, and New York Heart Association class IV heart
      failure (HF) treated with cardiac resynchronization therapy/defibrillator
      [CRT/D]) and non-Group B patients (LVEF <=30%, NDCM duration of >=9 months, and
      New York Heart Association class III HF treated with CRT/D) using real-world
      observational studies. OBJECTIVE: To compare outcomes in Center for Medicare &
      Medicaid Services Group B and non-Group B PP ICD patients. METHODS: OMNI was a 4
      year prospective observational study that enrolled 1464 PP ICD patients with a
      mean LVEF of 25%; 72% were men, 78% had class II-IV HF, and 66% had coronary
      disease. A total of 795 (54.3%) received ICDs, and 669 (45.7%) received CRT/Ds.
      Ventricular tachyarrhythmia therapy rates and mortality were compared over 39 +/-
      18.4 months. RESULTS: Twenty-five percent received ventricular tachyarrhythmia
      therapies, and 21.2% died within 4 years. Patient-year therapy rates were not
      significantly different for LVEF of 31%-35% (0.36 per year) vs <=30% (0.51/y) and
      CRT/D for class IV HF (0.21/y) vs class III HF (0.43 per year) but were lower for
      NDCM <9 months (0.3/y) vs >=9 months (0.85/y; P = .02). Four-year mortality was
      similar for LVEF 30%-35% (22.6%) vs <30% (24.4%) and NDCM <9 months (14.2%) vs
      >=9 months (12.3%) but was higher for CRT/D for class IV HF (48.6%) vs class III
      HF (27.4%) (P = .01). CONCLUSION: Patient-year ventricular tachyarrhythmia
      therapy rates did not differ between non-Group B and Group B PP ICD patients,
      though NDCM <9 months was significantly lower. Survival at 4 years was lowest in
      patients with New York Heart Association class IV HF treated with CRT/D and
      similar between all other non-Group B and Group B patients.

PMID- 22387372
TI  - Ryanodine receptor inhibition potentiates the activity of Na channel blockers
      against spontaneous calcium elevations and delayed afterdepolarizations in
      Langendorff-perfused rabbit ventricles.
AB  - BACKGROUND: Na channel blockers are effective in suppressing delayed
      afterdepolarizations (DADs) in isolated Purkinje fibers. However, in isolated
      mouse ventricular myocytes lacking calsequestrin, only those Na channel blockers
      that also inhibit type 2 ryanodine receptor channels were effective against
      spontaneous Ca elevation (SCaE) and DADs. OBJECTIVE: To test the hypothesis that
      combined Na channel and type 2 ryanodine receptor channel blocker ((R)
      propafenone) is more effective than a Na channel blocker (lidocaine) in
      suppressing SCaE and DADs in the intact rabbit ventricles. METHODS: We compared
      (R)-propafenone (3 MUmol/L) with lidocaine (50 MUmol/L) on SCaE and DADs by using
      epicardial optical mapping of intracellular calcium (Ca(i)) and membrane voltage
      in Langendorff-perfused rabbit hearts. SCaE and DADs were induced by rapid pacing
      trains and isoproterenol (0.3 MUmol/L) infusion. One arbitrary unit is equivalent
      to the Ca transient amplitude of paced beats. RESULTS: SCaEs were observed at the
      cessation of rapid pacing in all hearts at baseline. (R)-Propafenone nearly
      completely inhibited DADs and SCaE (0.04 arbitrary units [95% confidence interval
      0.02-0.06] vs 0.23 arbitrary units [95% confidence interval 0.18-0.28] at
      baseline; n = 6 hearts; P <.001). Lidocaine also significantly reduced the SCaE
      but was significantly (P <.05) less effective than (R)-propafenone. Both drugs
      increased the rise time of action potential upstroke and reduced conduction
      velocity to a similar extent, suggesting a significant inhibition of I(Na).
      CONCLUSIONS: Both Na channel blockers significantly reduced tachycardia-induced
      SCaEs in the rabbit ventricles, but (R)-propafenone was significantly more
      effective than lidocaine. These data suggest that type 2 ryanodine receptor
      inhibition potentiates the activity of Na channel blockers against SCaE and DADs
      in the intact hearts.

PMID- 22387374
TI  - Use of calcium channel blockers and Parkinson's disease.
AB  - Experimental evidence and case-control studies suggest that dihydropyridine
      calcium channel blockers (DiCCBs) may protect against Parkinson's disease. The
      authors conducted a historical cohort study in Denmark to investigate the
      association between DiCCB use and risk of Parkinson's disease (1998-2006).
      Individual-level data on filled drug prescriptions, diagnostic information, and
      covariates were linked between nationwide registries. Among DiCCB users, 173
      incident cases of Parkinson's disease were detected during 461,984 person-years
      of follow-up, compared with 5,538 cases during 17,343,641 person-years of follow
      up among nonusers. After adjustment for age, sex, year, propensity score, and use
      of other antihypertensive drugs and statins, DiCCB use was associated with a
      reduced risk of Parkinson's disease (rate ratio (RR) = 0.71, 95% confidence
      interval (CI): 0.60, 0.82). This association was not present in patients who had
      previously used DiCCBs (RR = 1.04, 95% CI: 0.87, 1.24). DiCCB users aged >=65
      years were at lower risk of Parkinson's disease than DiCCB users aged <65 years
      (RR = 0.59, 95% CI: 0.40, 0.85). Among patients with Parkinson's disease, DiCCB
      use was associated with reduced risk of death (adjusted RR = 0.66, 95% CI: 0.47,
      0.91) but not dementia (adjusted RR = 0.97, 95% CI: 0.60, 1.56). In conclusion,
      DiCCB exposure was associated with a reduced risk of incident Parkinson's
      disease, particularly in older patients, and with reduced mortality among
      patients with Parkinson's disease.

PMID- 22387375
TI  - Giving the right tug for migration: cadherins in tissue movements.
AB  - Dynamically regulated cell-cell adhesion is crucial for morphogenesis during
      embryonic development and tumor progression. The cadherins as calcium-dependent
      cell-cell adhesion proteins represent key molecules in these tissue movements.
      How cadherins serve in maintaining tissue cohesion during migration, facilitate
      cell-cell communication and promote signaling will be summarized in this review.

PMID- 22387373
TI  - Charting the travels of copper in eukaryotes from yeast to mammals.
AB  - Throughout evolution, all organisms have harnessed the redox properties of copper
      (Cu) and iron (Fe) as a cofactor or structural determinant of proteins that
      perform critical functions in biology. At its most sobering stance to Earth's
      biome, Cu biochemistry allows photosynthetic organisms to harness solar energy
      and convert it into the organic energy that sustains the existence of all
      nonphotosynthetic life forms. The conversion of organic energy, in the form of
      nutrients that include carbohydrates, amino acids and fatty acids, is
      subsequently released during cellular respiration, itself a Cu-dependent process,
      and stored as ATP that is used to drive a myriad of critical biological processes
      such as enzyme-catalyzed biosynthetic processes, transport of cargo around cells
      and across membranes, and protein degradation. The life-supporting properties of
      Cu incur a significant challenge to cells that must not only exquisitely balance
      intracellular Cu concentrations, but also chaperone this redox-active metal from
      its point of cellular entry to its ultimate destination so as to avert the
      potential for inappropriate biochemical interactions or generation of damaging
      reactive oxidative species (ROS). In this review we chart the travels of Cu from
      the extracellular milieu of fungal and mammalian cells, its path within the
      cytosol as inferred by the proteins and ligands that escort and deliver Cu to
      intracellular organelles and protein targets, and its journey throughout the body
      of mammals. This article is part of a Special Issue entitled: Cell Biology of
      Metals.

PMID- 22387378
TI  - Mechanism of action of therapeutic monoclonal antibodies: promises and pitfalls
      of in vitro and in vivo assays.
AB  - Therapeutic monoclonal antibodies (mAbs) are mostly used in cancer, as anti
      infectious agents and as immunomodulatory drugs, and are amongst the most active
      area of research and development in the pharmaceutical industry. This class of
      drugs comprises unconjugated antibodies or antibody fragments, antibody-drug
      conjugates, radio-immunoconjugates and bispecific/trispecific molecules. A better
      understanding of the mechanism of action of successful mAbs is fundamental for
      the selection of more active and less toxic mAbs of new generation. Furthermore
      reliable screening of new compounds at an early stage of preclinical development,
      for both efficacy and toxicity, should allow the selection of the best molecules
      at an early stage, and improve the rate of success of this class of drugs. Here
      we review the major methods that are employed for testing the activity of
      therapeutic mAbs in vitro and in vivo in small animal models and point out to
      some of the pitfalls in these assays.

PMID- 22387380
TI  - BIN1: a new biomarker to track ARVC?

PMID- 22387379
TI  - Probing the NADH- and Methyl Red-binding site of a FMN-dependent azoreductase
      (AzoA) from Enterococcus faecalis.
AB  - AzoA from Enterococcus faecalis is a member of the polymeric flavin-dependent
      NADH-preferred azoreductase group. Little is known about the binding and
      interaction of NADH and azo dye in the azoreductase group. A synergetic strategy
      based on computational prediction, reverse genetics validation coupled with site
      directed mutagenesis, and reconstruction of mutation network was used to
      investigate the binding and interaction of NADH and a model azo dye, Methyl Red,
      with AzoA. Methyl Red and NADH interacted in a unique binding mode in which the
      benzoic acid moiety of Methyl Red and the nicotinamide ring of NADH were not
      parallel to the flavin isoalloxazine ring, but lay against it at angles of ~45
      degrees  and ~35 degrees , respectively. The adenine ribose moiety of NADH was
      surrounded by loop l2 on chain B and alpha3 on chain A in a typical Rossmann
      fold. There were 12 and 19 amino acid residues that could participate in the
      binding of Methyl Red and NADH, respectively, especially the residues Tyr-129 and
      Asp-184. The functional perturbation effects of 13 residues, including Tyr-129
      and Asp-184, were mapped to reconstruct the mutation network, which confirmed the
      proposed binding modes and also provided insights into the interaction among
      NADH, FMN and Methyl Red.

PMID- 22387381
TI  - Postexercise recovery of the spatial QRS/T angle as a predictor of sudden cardiac
      death.
AB  - BACKGROUND: Postexercise measurement of heart rate (HR) recovery and QT interval
      dynamics provides prognostic information in various patient populations.
      OBJECTIVE: The purpose of this study was to assess whether the measurement of the
      spatial relationship between the depolarization and repolarization wavefronts
      (total cosine R-to-T [TCRT]) during the postexercise recovery phase would yield
      prognostic information. METHODS: The population consisted of 1297 patients (56 +/
      13 years; 67% men) who performed a clinically indicated bicycle stress test. The
      exercise-recovery hysteresis of TCRT was quantified from the 12-lead exercise
      electrocardiogram by measuring the TCRT/HR loop area bounded by the exercise and
      first 3-minute postexercise recovery curves. The HR-corrected TCRT/HR hysteresis
      was calculated by dividing the area with the HR decrement during the first 3
      minutes of recovery. HR recovery was measured at 1 minute postexercise recovery.
      End points were cardiac death and sudden cardiac death. RESULTS: During an
      average follow-up of 45 +/- 12 months, 74 patients died (5.7%); 35 (2.6%) were
      cardiac deaths and 24 (1.9%) were sudden cardiac deaths. Reduced TCRT/HR loop
      area and TCRT/HR hysteresis were associated with cardiac mortality (P <.001).
      After adjustments for clinical variables, including ejection fraction, TCRT/HR
      loop area remained an independent predictor of cardiac death (hazard ratio 5.6;
      95% confidence interval 1.6-19.1; P = .007) and sudden cardiac death (10.7; 95%
      confidence interval 1.4-83.7; P = .024). HR recovery did not remain a significant
      predictor in the multivariate analysis. CONCLUSIONS: Attenuated hysteresis of the
      depolarization and repolarization wavefronts during postexercise recovery is
      associated with an increased risk of cardiac and sudden cardiac death. Analysis
      of repolarization dynamics from exercise electrocardiogram represents a promising
      tool for risk stratification.

PMID- 22387382
TI  - A UV-vis study of the effects of alcohols on formation and stability of
      Mn(por)(O)(OAc) complexes.
AB  - Interactions of three different (acetato) (tetraarylporphyrinato) manganese (III)
      Mn(III)(por) with tetra-n-butylammonium hydrogen monopersulfate (n-Bu(4)NHSO(5)),
      in the presence of excess tetra-n-butylammonium acetate (n-Bu(4)NOAc) and in the
      absence or presence of various alcohols (alcohols=CH(3)OH, C(2)H(5)OH, i
      C(3)H(7)OH, t-C(4)H(9)OH) in CH(2)Cl(2), were monitored by their UV-vis spectral
      changes, under identical conditions, at room temperature. (Acetato)
      (tetrakispentafluorophenylporphyrinato) manganese (III) Mn(III)(tpfpp)(OAc) and
      (acetato) (tetramesitylporphyrinato) manganese (III) Mn(III)(tmp)(OAc) produced
      their corresponding high valent Mn(tpfpp)(O)(OAc) and Mn(tmp)(O)(OAc) both in the
      absence or presence of alcohols. Whereas, (acetato) (tetraphenylporphyrinato)
      manganese (III) Mn(III)(tpp)(OAc) only generated Mn(tpp)(O)(OAc) in the presence
      of less bulky alcohols. In the absence of alcohols or in the presence of t
      C(4)H(9)OH, the UV-vis spectra displayed a very weak sign of formation of
      Mn(tpp)(O)(OAc) complex. It was observed that alcohols generally increased the
      rate of formation of Mn-oxo species in accordance with their acidity or hydrogen
      bonding strength, and enhanced the stability of Mn-oxo complexes, as their size
      increases. Attempts are made to explain these effects. A mechanistic scheme is
      also suggested for the decomposition of HSO(5)(-) to O(2) and HSO(4)(-), through
      the formation and dimerization of Mn-oxo species.

PMID- 22387385
TI  - The 1alpha,25-dihydroxy-vitamin D3 reduces dengue virus infection in human
      myelomonocyte (U937) and hepatic (Huh-7) cell lines and cytokine production in
      the infected monocytes.
AB  - Dengue is the most important mosquito-borne viral infection in humans. Recent
      evidence suggests that vitamin D influences virus replication. In this work, the
      effect of vitamin D treatment on dengue virus infection in human hepatic Huh-7
      cells and on virus infection and cytokine production in the human monocytic U937
      cells was evaluated. Exposure to 1alpha,25-dihydroxy-vitamin D3, resulted in a
      significant reduction in the number of infected cells, in conditions where cell
      viability was not affected. Viral replication in monocytic cells was more
      susceptible to vitamin D3 than replication in the hepatic cells. Moreover,
      vitamin D3 significantly reduced the levels of proinflammatory cytokines (TNF
      alpha, IL-6, IL-12p70 and IL-1beta) produced by infected U937 cells. These
      results suggest that vitamin D3 may represent a potentially useful antiviral
      compound.

PMID- 22387386
TI  - Predicting sustained viral response to hepatitis C using a rapid and simple IL28B
      rs8099917 genotyping assay.
AB  - Recent studies showed that two single nucleotide polymorphisms (SNPs) (rs12979860
      and rs8099917) near the gene IL28B coding for IFNlambda3 were associated with the
      antiviral treatment response of the combination therapy of pegIFN plus RBV. We
      established the use of tetra-primer amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR) for detecting IL28B rs8099917 genotype (T>G)
      in 56 Chinese chronic hepatitis C patients infected with Hepatitis C Virus (HCV)
      genotype 1. The new assay showed 98.2% specificity, and was confirmed by direct
      sequencing. Among the 56 samples, TT genotype and TG genotype accounted for 80.4%
      (45/56) and 19.6% (11/56), respectively. GG genotype was not found. The
      proportion of responders in TT group was higher than that in TG group (68.9% vs.
      27.3%, p=0.029). For HCV clinical decision-making, using the new assay, rs8099917
      genotyping could provide similar information to rs12979860 genotyping due to a
      strong association between the two SNPs in Chinese patients. The assay system in
      this study can be implemented using basic laboratory equipments, making it
      convenient for clinical and research purposes.

PMID- 22387387
TI  - Comparison of enhanced bioluminescence energy transfer donors for protease
      biosensors.
AB  - Bioluminescence energy transfer (BRET) is a powerful tool for the study of
      protein-protein interactions and conformational changes within proteins. We
      directly compared two recently developed variants of Renilla luciferase (RLuc),
      RLuc2 and RLuc8, as BRET donors using an in vitro thrombin assay. The comparison
      was carried out by placing a thrombin-specific cleavage sequence between the
      donor luciferase and a green fluorescent protein (GFP(2)) acceptor. Substitution
      of native RLuc with the RLuc mutants, RLuc2 and 8, in a BRET(2) fusion protein
      increased the light output by a factor of ~10. Substitution of native RLuc with
      either of the RLuc mutants resulted in a decrease in BRET(2) ratio by a factor of
      ~2 when BRET(2) components were separated by the thrombin cleavage sequence.
      BRET(2) ratios changed by factors of 18.8+/-1.2 and 18.2+/-0.4 for GFP(2)-RG
      RLuc2 and GFP(2)-RG-RLuc8 fusion proteins, respectively, on thrombin cleavage
      compared to 28.8+/-0.20 for GFP(2)-RG-RLuc. The detection limits for thrombin
      were 0.23 and 0.26 nM for RLuc2 and RLuc8 BRET(2) systems, respectively, and 15
      pM for GFP(2)-RG-RLuc. However, overall, the mutant BRET systems remain more
      sensitive than FRET and brighter than standard BRET(2).

PMID- 22387388
TI  - Fluorogenic substrates with single fluorophores for nucleic acid-modifying
      enzymes: design principles and new applications.
AB  - Nucleic acid-modifying enzymes are widely used in numerous applications. Many of
      these proteins are also important drug targets. Thus, better assays for the
      evaluation of their activities are always needed and are continuously being
      developed. Recently, I reported on a set of assays for several DNA-modifying
      enzymes (polymerases, endonucleases, and ligase) based on simple, hairpin-type
      oligonucleotide substrates labeled with a single fluorophore (Anal. Biochem. 412
      (2011) 229-236). The present paper reports further studies on the mechanism of
      action of these substrates. It was assumed that the single fluorophore of these
      substrates is substantially quenched by stacking onto the terminal base(s) of the
      duplex, and that any perturbation of that stacking causes an increase in
      fluorescence. Based on this assumption, substrates of the same type for a variety
      of additional enzymes were developed and tested. The new assays described herein
      are for T4 polynucleotide kinase, the DNA repair enzymes uracil-DNA glycosylase
      (UDG) and formamido-pyrimidine-DNA glycosylase (FPG), 3'-5' exonucleases, and
      enzymes with template-independent terminal transferase activity such as Taq
      polymerase. All of these molecules are easy to synthesize, and similar substrates
      for other enzymes can rapidly be designed based on the principles outlined in
      this work.

PMID- 22387389
TI  - On-the-resin N-terminal modification of long synthetic peptides.
AB  - Here we present a highly efficient protocol for on-the-resin coupling of
      fluorescent dyes or other functional groups to the N-termini of synthetic
      peptides prior to cleavage and deprotection. The protocol avoids expensive
      preactivated dyes and instead employs carboxylated dyes activated by large
      amounts of coupling reagents. The protocol was used to label peptides with low
      reactivity such as long hydrophobic peptides and peptides with strong tendencies
      to form sterically shielding structures or aggregates in solution. In all cases,
      the yields far exceeded those from commercially available preactivated compounds.

PMID- 22387390
TI  - Molecular cloning of large alternative transcripts based on comparative
      phylogenetic analysis and exploration of an EST database.
AB  - In animals, a gene may be 50 kb or over and contain multiple alternative
      transcripts with sequences that are not experimentally validated. Under these
      special circumstances, PCR-based cloning may become very difficult. Here a simple
      cloning strategy is described using the mNLRC5 gene as an example. We performed
      comparative phylogenetic analysis between murine and human NLR protein families
      to anchor the translation start codon, searched an EST database with the 3' end
      of the genomic DNA sequence to obtain ESTs from the farthest 3' end of the gene,
      and isolated the full-length CDS of the mNLRC5 of about 6 kb through conventional
      RT-PCR and 3' RACE.

PMID- 22387391
TI  - Duplexed iMALDI for the detection of angiotensin I and angiotensin II.
AB  - An immuno-Matrix Assisted Laser Desorption/Ionization (iMALDI) method has been
      developed using anti-IgG beads to capture anti-AngI and anti-AngII antibodies,
      which are incubated with a ~50MUL plasma sample to which known amounts of stable
      isotope-labeled AngI and AngII have been added. After a short incubation time,
      the beads are washed, placed directly on a MALDI target, and analyzed by mass
      spectrometry (MS) and tandem mass spectrometry (MS/MS). The iMALDI assay
      developed can detect and quantify angiotensin I (AngI) and angiotensin II (AngII)
      in human plasma. This assay has a Limit of Detection (LOD) of ~10amol/MUL (or
      ~13pg/mL AngI and ~11pg/mL AngII), at a S/N of 2:1, using only one-tenth of the
      antibody beads which were incubated with a 50-MUL plasma sample. This LOD is
      within the relevant range of patient samples. Little or no angiotensin generation
      period is required, resulting in a rapid assay. Correlation coefficients for the
      standard curves are >0.99, with a linear range of 4-100fmol/MUL (5-130ng/mL) and
      100-2500amol/MUL (106-2614pg/mL) for AngI and AngII, respectively. This duplexed
      assay can quantify AngI and AngII peptide levels simultaneously, in plasma from
      normotensive and hypertensive patients. The assay can detect changes in the
      levels of these peptides over time, which will allow quantitation of plasma renin
      and ACE activities.

PMID- 22387392
TI  - Inhibition of interleukin-17 promotes differentiation of CD25- cells into stable
      T regulatory cells in patients with autoimmune hepatitis.
AB  - BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) have reduced numbers
      and function of CD4+CD25(high)FOXP3+ T regulatory cells (Tregs). Tregs can be
      generated from CD25- (ngTreg) cells, which suppress the immune response less
      efficiently than Tregs. We investigated whether their differentiation into T
      helper (Th)17 cells, an effector subset that has the same CD4+ progenitors as
      Tregs, accounts for the reduced suppressive functions of ngTregs. We investigated
      whether blocking interleukin (IL)-17 increased the immunosuppressive activity of
      Tregs. METHODS: ngTregs were generated from 36 patients with AIH and 23 healthy
      subjects (controls). During Treg differentiation, expression of IL-17 was
      inhibited by physical removal of IL-17-secreting cells, exposure to recombinant
      transforming growth factor beta or neutralizing antibodies against IL-6 and IL
      1beta (to promote differentiation of ngTregs vs Th17 cells), small inhibitory
      RNAs specific for the Th17 transcription factor RORC, or a combination of all
      these approaches. RESULTS: ngTregs from patients with AIH contained greater
      proportions of IL-17+ and RORC+ cells than Tregs from controls. All approaches to
      inhibit IL-17 increased expression of FOXP3 by ngTregs and their suppressive
      functions. Inhibition of IL-17 led to development of ngTregs that were
      phenotypically stable and did not acquire proinflammatory properties after
      exposure to IL-6 and IL-1beta. CONCLUSIONS: Blocking Th17 allows ngTregs to
      differentiate into functionally stable immune inhibitory cells; this approach
      might be developed for therapy of patients with AIH.

PMID- 22387393
TI  - p28(GANK) prevents degradation of Oct4 and promotes expansion of tumor-initiating
      cells in hepatocarcinogenesis.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is believed to arise from tumor
      initiating cells (T-ICs), although little is known about their stem cell-like
      properties. METHODS: We quantified levels of p28(GANK) (Gankyrin), OV6, and Oct4
      in 130 human HCC samples using immunohistochemistry. Magnetic-activated cell
      sorting was used to isolate OV6+ HCC cells. T-IC properties were evaluated by
      quantitative reverse-transcription polymerase chain reaction, flow cytometry, and
      spheroid formation. We used a coimmunoprecipitation assay to study interactions
      among p28(GANK), Oct4, and WWP2. Tumorigenicity and pulmonary metastasis were
      examined in nonobese diabetic and severe combined immunodeficient mice. RESULTS:
      In HCC samples, high levels of p28(GANK) correlated with expansion of OV6+ tumor
      cells; the combination of high levels of p28(GANK) and OV6 was associated with
      progression of HCC. p28(GANK) was predominantly expressed in liver T-ICs,
      isolated by magnetic sorting, and undifferentiated primary HCC spheroids.
      Increased levels of p28(GANK) in T-ICs increased their percentages in HCC
      samples, expression of stem cell genes, self-renewal potential, chemoresistance
      in vitro, and tumorigenicity and ability to develop into pulmonary metastases in
      mice. Conversely, knockdown of p28(GANK) reduced their T-IC properties. p28(GANK)
      likely activates liver T-ICs by impeding ubiquitination and degradation of the
      transcription factor Oct4 by WWP2. In support of this concept, levels of
      p28(GANK) correlated with those of Oct4 in HCC samples. CONCLUSIONS: p28(GANK)
      activates and maintains liver T-ICs in HCCs by preventing degradation of Oct4.
      Inhibitors of p28(GANK) might therefore be developed to inactivate T-ICs and slow
      tumor progression.

PMID- 22387395
TI  - Deletion of psbJ leads to accumulation of Psb27-Psb28 photosystem II complexes in
      Thermosynechococcus elongatus.
AB  - The life cycle of Photosystem II (PSII) is embedded in a network of proteins that
      guides the complex through biogenesis, damage and repair. Some of these proteins,
      such as Psb27 and Psb28, are involved in cofactor assembly for which they are
      only transiently bound to the preassembled complex. In this work we isolated and
      analyzed PSII from a DeltapsbJ mutant of the thermophilic cyanobacterium
      Thermosynechococcus elongatus. From the four different PSII complexes that could
      be separated the most prominent one revealed a monomeric Psb27-Psb28 PSII complex
      with greatly diminished oxygen-evolving activity. The MALDI-ToF mass spectrometry
      analysis of intact low molecular weight subunits (<10kDa) depicted wild type PSII
      with the absence of PsbJ. Relative quantification of the PsbA1/PsbA3 ratio by LC
      ESI mass spectrometry using (15)N labeled PsbA3-specific peptides indicated the
      complete replacement of PsbA1 by the stress copy PsbA3 in the mutant, even under
      standard growth conditions (50MUmol photons m(-2) s(-1)). This article is part of
      a Special Issue entitled: Photosynthesis Research for Sustainability: from
      Natural to Artificial.

PMID- 22387394
TI  - The nucleotide synthesis enzyme CAD inhibits NOD2 antibacterial function in human
      intestinal epithelial cells.
AB  - BACKGROUND & AIMS: Polymorphisms that reduce the function of nucleotide-binding
      oligomerization domain (NOD)2, a bacterial sensor, have been associated with
      Crohn's disease (CD). No proteins that regulate NOD2 activity have been
      identified as selective pharmacologic targets. We sought to discover regulators
      of NOD2 that might be pharmacologic targets for CD therapies. METHODS: Carbamoyl
      phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) is an enzyme
      required for de novo pyrimidine nucleotide synthesis; it was identified as a NOD2
      interacting protein by immunoprecipitation-coupled mass spectrometry. CAD
      expression was assessed in colon tissues from individuals with and without
      inflammatory bowel disease by immunohistochemistry. The interaction between CAD
      and NOD2 was assessed in human HCT116 intestinal epithelial cells by
      immunoprecipitation, immunoblot, reporter gene, and gentamicin protection assays.
      We also analyzed human cell lines that express variants of NOD2 and the effects
      of RNA interference, overexpression and CAD inhibitors. RESULTS: CAD was
      identified as a NOD2-interacting protein expressed at increased levels in the
      intestinal epithelium of patients with CD compared with controls. Overexpression
      of CAD inhibited NOD2-dependent activation of nuclear factor kappaB and p38
      mitogen-activated protein kinase, as well as intracellular killing of Salmonella.
      Reduction of CAD expression or administration of CAD inhibitors increased NOD2
      dependent signaling and antibacterial functions of NOD2 variants that are and are
      not associated with CD. CONCLUSIONS: The nucleotide synthesis enzyme CAD is a
      negative regulator of NOD2. The antibacterial function of NOD2 variants that have
      been associated with CD increased in response to pharmacologic inhibition of CAD.
      CAD is a potential therapeutic target for CD.

PMID- 22387396
TI  - Refined structure-based simulation of plant light-harvesting complex II: linear
      optical spectra of trimers and aggregates.
AB  - Linear optical spectra of solubilized trimers and small lamellar aggregates of
      the major light-harvesting complex II (LHCII) of higher plants are simulated
      employing excitonic couplings and site energies of chlorophylls (Chls) computed
      on the basis of the two crystal structures by a combined quantum
      chemical/electrostatic approach. A good agreement between simulation and
      experiment is achieved (except for the circular dichroism in the Chl b region),
      if vibronic transitions of Chls are taken into account. Site energies are further
      optimized by refinement fits of optical spectra. The differences between refined
      and directly calculated values are not significant enough to decide, whether the
      crystal structures are closer to trimers or aggregates. Changes in the linear
      dichroism spectrum upon aggregation are related to site energy shifts of Chls
      b601, b607, a603, a610, and a613, and are interpreted in terms of conformational
      changes of violaxanthin and the two luteins involving their ionone rings. Chl
      a610 is the energy sink at 77K in both conformations. An analysis of absorption
      spectra of trimers perpendicular and parallel to the C(3)-axis (van Amerongen et
      al. Biophys. J. 67 (1994) 837-847) shows that only Chl a604 close to neoxanthin
      is significantly reoriented in trimers compared to the crystal structures.
      Whether this pigment is orientated in aggregates as in the crystal structures,
      can presently not be determined faithfully. To finally decide about pigment
      reorientations that could be of relevance for non-photochemical quenching,
      further polarized absorption and fluorescence measurements of aggregates or
      detergent-depleted LHCII would be helpful. This article is part of a Special
      Issue entitled: Photosynthesis Research for Sustainability: from Natural to
      Artificial.

PMID- 22387397
TI  - Luminescence of singlet oxygen in photosystem II complexes isolated from
      cyanobacterium Synechocystis sp. PCC6803 containing monovinyl or divinyl
      chlorophyll a.
AB  - The luminescence spectrum of singlet oxygen produced upon excitation at 674nm in
      the photochemically active photosystem II (PS II) complexes isolated from
      cyanobacterium Synechocystis sp. PCC 6803 containing different types of
      chlorophyll, i.e., monovinyl (wild-type) or divinyl (genetically modified)
      chlorophyll a. The yield of singlet oxygen, estimated using methylene blue as the
      standard, from the divinyl-chlorophyll PS II complex was more than five times
      greater than that from the monovinyl-chlorophyll PS II complex. These results are
      consistent with the observed difference in the sensitivity towards high intensity
      of light between the two cyanobacterial strains. The yield of singlet oxygen
      appeared to increase with the level of triplet chlorophyll, in the divinyl
      chlorophyll PS II complex. This article is part of a Special Issue entitled:
      Photosynthesis Research for Sustainability: from Natural to Artificial.

PMID- 22387399
TI  - Botulinum toxin A in the treatment of spasticity - An open label study.
AB  - PURPOSE: To assess the efficacy of botulinum toxin type A in spasticity in upper
      motor neuron syndromes. METHODS: Twenty-three patients with spasticity resulted
      from stroke-related hemiplegia, transverse myelitis and multiple sclerosis took
      part in the study. Following the history and physical examinations of the
      patients, injections of botulinum toxin-A were applied. The dose ranged from 80
      to 400 mouse unit (MU) depending on the size of the muscle injected. In all
      patients, spasticity, spasms and pain were measured using the Ashworth Scale,
      Spasm Frequency Score, and Visual Analogue Scale prior to the therapy, at the 1st
      week, 1st month and 3rd month of the therapy. RESULTS: In all patients, botulinum
      toxin type A led to a significant decrease in spasticity, spasms and pain after
      the 1st week, 1st and 3 rd months of the treatment when compared to the baseline
      values (p<0.001). No significant side effects or complications were observed.
      CONCLUSION: Our results have demonstrated that botulinum toxin type A is
      effective in the management of patients with spasticity due to stroke-related
      hemiplegia, transverse myelitis and multiple sclerosis, without major adverse
      effects.

PMID- 22387398
TI  - Imaging lysosomal enzyme activity in live cells using self-quenched substrates.
AB  - Endocytosis, the internalization and transport of extracellular cargo, is an
      essential cellular process. The ultimate step in endocytosis is the intracellular
      degradation of extracellular cargo for use by the cell. While live cell imaging
      and single particle tracking have been well-utilized to study the internalization
      and transport of cargo, the final degradation step has required separate
      biochemical assays. We describe the use of self-quenched endocytic cargo to image
      the intracellular transport and degradation of endocytic cargo directly in live
      cells. We first outline the fluorescent labeling and quantification of two common
      endocytic cargos: a protein, bovine serum albumin, and a lipid nanoparticle, low
      density lipoprotein. In vitro measurements confirm that self-quenching is a
      function of the number of fluorophores bound to the protein or particle and that
      recovery of the fluorescent signal occurs in response to enzymatic degradation.
      We then use confocal fluorescence microscopy and flow cytometry to demonstrate
      the use of self-quenched bovine serum albumin with standard fluorescence
      techniques. Using live cell imaging and single particle tracking, we find that
      the degradation of bovine serum albumin occurs in an endo-lysosomal vesicle that
      is positive for LAMP1.

PMID- 22387400
TI  - Body fat percent and fat distribution parameters in rheumatic diseases.
AB  - Alterations in body composition in chronic rhematologic disorders have been
      associated with decreased strength, altered energy metabolism and immunologic
      compromise and may provide a useful indicator of the severity of the disease.
      However, results of anthropometric parameter studies have been equivocal. The
      purpose of this study, was to compare body composition parameters of patients
      with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) with those of
      healthy controls. Mean age, height, weight and body mass index (BMI) of patients
      with RA were not found to be different from those of the controls. BMI, body fat
      percent (BFP) were found to be high in patients with AS, but the differences
      between this two parameters of AS patients and controls were not statistically
      significant. Mean BFP of patients with RA was higher than the control subjects,
      but only the difference between female patients with RA and controls was
      statistically significant. Mean lean body mass (LBM) was slightly lower in male
      and female patients with RA compaired to the healthy controls. LBM of AS patients
      was found to be similar with that of the controls. Upper/lower body fat ratio
      (U/L BFR) and central/peripheral body fat ratio (C/P BFR) were higher in male
      patients with RA, but there were no differences between patients and controls.
      U/L BFR and C/P BFR body fat ratios were higher in AS patients. But, only the
      differences between C/P body fat distribution of AS patients and control subjects
      was statistically significant.  The results obtained from this preliminary report
      show some anthropometric parameters of RA and AS patients can differ from those
      of the healthy controls. Future investigations are needed to determine the
      metabolic alterations causing the changes in body composition.

PMID- 22387401
TI  - The NASS lumbar spine outcome assessment instrument: Large sample assessment and
      sub-scale identification.
AB  - BACKGROUND: Accurately assessing patient-reported pain and functional ability is
      essential to measuring quality of care. PURPOSE: Evaluating the instruments used
      in assessing quality of care is often overlooked. The North American Spine
      Society Lumbar Spine Outcome Assessment (NASS-LS) instrument measures patient
      reported pain and function in a combined scale. We evaluated the original
      instrument and assessed separate pain and function subscales based on a set of
      the items in the original instrument. STUDY DESIGN/SETTING: Data were collected
      from seven spine clinics in the United States participating in the Spinal Surgery
      Consortium for Outcomes Research Project. Consenting patients were enrolled in
      the project and asked to complete the NASS instrument when arriving for a
      surgical consult. PATIENT SAMPLE: Data from 811 lumbar spine patients were used.
      METHODS: Analyses were conducted on the original instrument to determine its
      internal consistency and to determine the structural existence of any underlying
      scales. Internal consistency of the original and new scales were assessed with
      Cronbach's coefficient alpha. RESULTS: The original scale was found to be a
      useful measure of pain and functional ability. Important subscales of pain and
      functional ability were also identified allowing us to report more meaningful
      results. CONCLUSION: The original instrument is useful for assessing low-back
      pain and function as a combined concept. The separate pain and function scales
      may prove useful assessing varying outcome levels and/or different decisions
      about subsequent follow-up care.

PMID- 22387402
TI  - Electrodiagnosis and outcome prediction for persons with upper limb symptoms: A
      pilot study.
AB  - CONTEXT: In the evaluation of patients with upper limb symptoms, electrodiagnosis
      (EDX) provides valuable information regarding neurological disorders such as
      radiculopathies and entrapment neuropathies. What is less clear from the
      literature is whether or not EDX findings contribute to the prediction of
      outcomes. OBJECTIVE: In order to examine the relationship between EDX findings
      and outcomes, this pilot study was conducted. METHODS: Thirty-eight patients with
      neck and upper limb symptoms who underwent EDX testing and standardized data
      collection as part of a previously conducted prospective study were contacted by
      telephone a mean of 30 months after testing to determine their outcomes. Patients
      were classified into three categories according to EDX findings: i) 15 had
      radiculopathies, ii) 13 had normal studies, and iii) 10 had other
      electrodiagnostic findings. Primary outcome variables of interest were the
      interval verbal pain rating scale and a subjective report of symptom improvement.
      RESULTS: None of the patients with radiculopathies or normal studies worsened,
      whereas 30% of persons with other findings on EDX significantly worsened.
      CONCLUSIONS: The findings from this small pilot study raise many questions
      regarding electrodiagnosis and its relationship to outcome. A larger prospective
      study is necessary to fully examine this relatively unexplored but potential use
      for EDX testing.

PMID- 22387403
TI  - Hamstring shortening in healthy adults.
AB  - Hamstring shortening (HS) causes changes in the posture and walking ability in
      spastic children, however, there are no studies defining the abnormalities in
      patellar alignment in individuals with HS.Twenty-five patients with a primary
      complaint of anterior knee pain, having HS detected at physical examination, and
      11 healthy individuals without any HS or knee discomfort as a control group are
      included in this study. Serial x-rays of the spine, pelvis and knee are taken and
      knee x-rays are evaluated for the position of the patella in both groups.In
      patients with Knee Extension Deficit (KED) >= 60 degrees , the Blackburne-Peel
      ratio is lower and the Insall-Salvati ratio is higher than the other groups,
      denoting a cephalic location of the patella (p < 0.05). There are no changes in
      the congruency and sulcus angles between the HS and control groups. Vertebral and
      pelvic changes correlate well with the literature, confirming that significant
      alterations occur after 60 degrees  of KED in adults.The extensor mechanism of
      the knee is affected and patella is located higher than normal in patients with
      severe HS, which may be a cause for knee discomfort. In the light of these
      findings, a routine knee extension deficit examination can be suggested in the
      initial evaluation of knee discomfort.

PMID- 22387404
TI  - The rater reliability of assessments of symptom provocation in patients with low
      back pain.
AB  - The primary purpose of this study was to test the inter-rater reliability of
      assessments by physical therapists using the movement testing protocol from the
      Movement System Balance (MSB) approach developed by Sahrmann for classification
      of low back pain. A second purpose was to determine if attendance at a continuing
      education course improves reliability. A convenience sample of 37 patients with
      low back pain (mean age = 37.2 SD = 13.6, range = 20 - 63) participated. Each
      patient was examined by a pair of examiners. One examiner pair had both attended
      a three day continuing education course and one pair had not. Within each pair of
      examiners, separate examinations of the same subject were done using 16 movement
      tests. The examiners made a decision whether the test provoked symptoms and which
      movement (flexion, extension, or rotation) was the cause. Kappa coefficients and
      proportionate agreement in positive and negative decisions were calculated. A
      paired t-test showed no difference between the agreement of the examiner pairs
      for each movement test based on type of examiner training so the results were
      combined for the rest of the analysis. The range of kappas statistics for the
      movement tests (0.02-0.62) indicated 6 of the 16 tests showed satisfactory
      reliability. The results suggest that that clinicians attending continuing
      education courses or learning these techniques from printed materials or videos
      should apply clinical decisions based on these movement tests judiciously.

PMID- 22387405
TI  - Radiological abnormalities of the lumbosacral spine in young male individuals.
AB  - The purpose of this study was to determine the overall incidence and distribution
      of lumbosacral congenital abnormalities in healthy and active young male
      individuals. The study population consisted of 503 healthy young male candidates
      for sports training. Lumbosacral transitional vertebral (LSTV) abnormalities were
      found in 37 (7.4%) of subjects and were unilateral in 14 (2.8%) subjects
      (lumbarization/sacralization). Lumbar rotoscoliosis (LRS) was present in 14
      (2.8%) subjects and facet asymmetry in one subject. LSTV and LRS together were
      present in 3 subjects. Spina Bifida Occulta (SBO) was present in 107 of 503
      candidates (21.4%). The distribution of SBO throughout vertebra levels was as
      follows: 86 only in S1, 11 in S1+S2, 9 in L5, 1 in L5+S1. SBO and LSTV were
      present together in 8 subjects. SBO and LRS were present together in three
      subjects. 356 (70.4%) subjects had normal lumbosacral radiographs.  Our study
      results support the notion that SBO is a common lumbosacral abnormality
      especially in young male healthy individuals.

PMID- 22387406
TI  - Quantification of the loading characteristics of the upper body and back
      extension strength on a variable angle Roman chair.
AB  - The purpose of this study was to quantify the loading characteristics of the
      upper body during variable angle Roman chair (VARC) exercise and to compare back
      extension strength outputs obtained from a VARC to a criterion measure (lumbar
      dynamometer). For twenty-four healthy volunteers (age, 22.7 +/- 3.2 years), the
      load attributed to the upper body and isometric back extension strength were
      measured twice at six positions over a full range of lumbar flexion on a VARC. In
      addition, isometric back extension strength was measured at seven positions over
      a full range of lumbar flexion on a lumbar dynamometer. Test-retest reliability
      was high for measures of the load attributed to the upper body (r = 0.99) and
      isometric strength (r = 0.96 to 0.97) on the VARC. The load attributed to the
      upper body increased from the most flexed to most extended position, while
      isometric strength increased from the most extended to the most flexed position
      on the VARC. Average VARC and dynamometer strength values were highly correlated
      (r = 0.90), but were lower on the VARC than on the dynamometer (888.4 +/- 249.8 N
      vs. 1050.0 +/- 438.5 N, respectively; p < 0.05).

PMID- 22387407
TI  - The role of therapeutic exercise in treating instability-related lumbar spine
      pain: A systematic review.
AB  - STUDY DESIGN: A systematic review of clinical trials. OBJECTIVE: To determine the
      effectiveness of therapeutic exercise in the treatment of instability-related
      lumbar spine pain. BACKGROUND: Segmental instability of the lumbar spine
      contributes to the overwhelming incidence of back pain and disability. The
      extensive range of exercises proposed to treat segmental instability is
      indicative of the lack of agreement as to the most efficacious management
      approach. METHODS: A search of MEDLINE (1966- April 2002), the Cumulative Index
      of Nursing and Allied Health Literature (CINAHL) (1982- April 2002) databases was
      performed. The searches were restricted to articles that used human subjects and
      were published in English. Key words utilized for searches included, "lumbar
      stability", "segmental instability of the lumbar spine", "spinal stability", "low
      back exercises", and "treatment of lumbar instability". The aforementioned key
      words were combined with "clinical trial" in an attempt to locate studies that
      were primary sources and included original data. RESULTS: The clinical trials
      analyzed varied considerably in the type of therapeutic exercise evaluated.
      However, it has been demonstrated that therapeutic exercise can be beneficial in
      reducing pain and improving function in patients presenting with instability
      related lumbar spine pain. CONCLUSION: Although the reviewed clinical trials have
      demonstrated the effectiveness of therapeutic exercise in ameliorating pain and
      disability, the variations in methodologies of the studies reviewed makes it
      difficult to speculate which specific exercises would be the most beneficial.

PMID- 22387408
TI  - Is seladin-1 really a selective Alzheimer's disease indicator?
AB  - Selective Alzheimer's Disease Indicator-1 (Seladin-1) was originally identified
      by its down-regulation in the brains of Alzheimer's disease (AD) patients. Here,
      we re-examine existing data and present new gene expression data that refutes its
      role as a selective AD indicator. Furthermore, we caution against the use of the
      name "Seladin-1" and instead recommend adoption of the approved nomenclature,
      3beta-hydroxysterol Delta24-reductase (or DHCR24), which describes its catalytic
      function in cholesterol synthesis. Further work is required to determine what
      link, if any, exists between DHCR24 and AD.

PMID- 22387409
TI  - Improvement of semantic categorization through procedural learning in Alzheimer's
      disease.
AB  - This paper studies the procedural learning of semantic categorization in 20
      patients with mild Alzheimer's disease (AD). We investigated if the AD group was
      able to develop semantic skill using a cognitive procedural task, developed in
      our laboratory, by applying a manual and serial reaction time paradigm to
      semantic categorization. The AD group had markedly lower scores than the normal
      group on semantic categorization and had longer reaction times than the control
      subjects. Nevertheless, we observed an improvement of semantic categorization
      reaction times over time with practice, even with new verbal material to
      categorize, in both the AD and control groups. These results support the notion
      that AD patients are able to acquire semantic skill without awareness simply by
      repeated exposure, although their semantic accuracy will not reach normal levels.

PMID- 22387410
TI  - Context-dependent toxicity of amyloid-beta peptides on mouse cerebellar cells.
AB  - Alzheimer's disease (AD) is the major cause of dementia in old people. AD
      pathology is characterized by amyloid-beta (Abeta) deposits in several regions of
      the brain, and links have been hypothesized between Abeta toxicity and apoptosis.
      Cerebellar granule cells (CGCs) have been widely used as in vitro tools for
      molecular studies correlating apoptosis with AD, although the cerebellum is a
      relatively spared area of the brain in vivo. We have used mixed neuronal-glial
      cerebellar cultures (NGCCs) and organotypic cerebellar cultures (OCCs) obtained
      from postnatal mice to assess the toxic effect of the Abeta oligomer 1-40 (Abeta1
      40) after propidium iodide uptake in vitro. Our results demonstrate that NGCCs,
      which are primarily composed of CGCs, are resistant to Abeta1-40 challenge (5-10
      MUM) when cultured in physiological (5 mM) extracellular KCl ([K+]e)
      concentrations, i.e., in a condition in which CGCs undergo full maturation.
      Conversely, when 10 MUM Abeta1-40 is given to NGCCs cultured in elevated (25 mM)
      [K+]e (and thus maintained in an immature state), there is a statistically
      significant increase in cell death. Cell death is by apoptosis, as demonstrated
      by ultrastructural examination. OCCs are resistant to Abeta challenge in any of
      the conditions tested (variation of [K+]e, presence or absence of serum, or
      addition of the neprilysin blocker phosphoramidon). Altogether these observations
      lead us to conclude that cerebellar cells in an organotypic context may be less
      susceptible to damage by Abeta, raising the question whether isolated CGCs are a
      reliable assay in drug discovery studies of AD.

PMID- 22387411
TI  - From anti-Parkinson's drug rasagiline to novel multitarget iron chelators with
      acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective
      properties for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a multifactorial syndrome involving a complex array
      of different, while related, factors in its progression. Accordingly, novel
      approaches that can simultaneously modulate several disease-related targets hold
      great promise for the effective treatment of AD. This review describes the
      development of novel hybrid molecules with multimodal activity, including: i)
      M30, the brain permeable selective monoamine oxidase (MAO)-A and -B inhibitor
      with chelating and neuroprotective activity; ii) HLA20, a brain permeable metal
      chelator with neuroprotective activity; iii) HLA20A, an acetylcholinesterase
      (AChE) inhibitor with site-activated chelating and neuroprotective activity; iv)
      M30D, an AChE and MAO-A and -B inhibitor with site-activated chelating and
      neuroprotective activity; and v) analogs of the neuroprotective aminoacid
      peptide, NAPVSIPQ. HLA20A and M30D act as pro-chelators and can be activated to
      liberate their respective active chelators HLA20 and M30 through pseudo
      inhibition of AChE. We first discuss the knowledge and structure-based strategy
      for the rational design of these novel compounds. Then, we review our recent
      studies on these drug candidates, regarding their wide range in vitro and in vivo
      activities, with emphasis on antioxidant-chelating potency and AchE and MAO-A and
      -B inhibitory activity, as well as neuroprotective/neurorescue effects. Finally,
      we discuss the diverse molecular mechanisms of action of these compounds with
      relevance to AD, including modulation of amyloid-beta and amyloid-beta protein
      precursor expression/processing; induction of cell cycle arrest; inhibition of
      neuronal death markers; and upregulation of neurotrophic factors, as well as
      activation of protein kinase signaling pathways.

PMID- 22387412
TI  - Left main bronchus foreign body masquerading as diaphragmatic hernia in an adult
      patient.
AB  - OBJECTIVE: Foreign body aspiration is quite uncommon in the adults. It can be a
      life-threatening situation and it often requires a high index of suspicion,
      because the diagnosis can be obscure. PRESENTATION OF CASE: We present a case of
      food aspiration by a 31-year old female patient, masquerading as diaphragmatic
      hernia, for the first time in the literature. DISCUSSION: Foreign body aspiration
      may escape diagnosis, especially if there is no recollection of the episode.
      CONCLUSION: The thoracic surgeon may be suspicious of this condition, even if the
      patient history and imaging obscure the clinical picture.

PMID- 22387413
TI  - Liver metastases, a rare cause of portal hypertension and stoma bleeding. Brief
      review of literature.
AB  - INTRODUCTION: Portal hypertension is an unusual complication of liver metastases,
      which is frequently occurring in malignant disease. Portal hypertension may cause
      oesophageal varices and also stoma varices (colostomy and ileostomy). Oesophageal
      varices and bleeding from these varices have been frequently reported in
      literature. Stomal varices have also been reported in literature mostly
      associated with liver cirrhosis. These stomal varices lead to the massive
      bleeding causing morbidity and mortality. Portal hypertension is a pathological
      increase in portal pressure gradient (the difference between pressure in the
      portal and inferior vena cava veins). It is either due to an increase in portal
      blood flow or an increase in vascular resistance or combination of both. In liver
      cirrhosis, the primary factor leading to portal hypertension is increase in
      portal blood flow resistance and later on development of increased portal blood
      flow. It has been postulated that in liver metastasis the increase in portal flow
      resistance occurs at any site within portal venous system as a consequence of
      mechanical architectural disturbance. PRESENTATION OF CASE: We report a case of a
      64 year old gentleman who developed portal hypertension due to secondary
      metastases from colorectal cancer. He subsequently developed bleeding varices in
      his end colostomy. DISCUSSION: We believe that the combination of extensive
      metastases and chemotherapy induced portal hypertension in our patient.
      CONCLUSION: Our case and other literature review highlight that the recurrent
      bleeding stoma associated with colorectal cancer should be investigated for
      portal hypertension.

PMID- 22387414
TI  - A locally aggressive solitary fibrous tumor of the leg: Case report and
      literature review.
AB  - INTRODUCTION: The solitary fibrous tumor (SFT) is a rare soft tissue tumor with a
      substantially benign clinical behavior. However, malignant neoplasms with local
      recurrence or distant metastases have been reported. PRESENTATION OF THE CASE:
      The authors present a case of an aggressive SFT of the leg, in a 55 years old
      Caucasian man. Radiological, histological and molecular findings are reported.
      The differential diagnosis, therapy and outcome of this rare tumor are also
      discussed. DISCUSSION: An extensive review of literature showed SFT's clinical
      behavior as substantially benign, anyway aggressive or malignant neoplasms have
      been described. The potential risk of local recurrence and distant metastasis
      thus suggests wide surgical resection and careful long-term follow-up.
      Differential diagnosis may be quite laborious as SFT can mimic a variety of
      benign and malignant mesenchymal tumors; immunohistochemical analysis for CD34,
      CD99, vimentin and bcl-2 is then mandatory. CONCLUSION: Our clinical experience
      confirmed that SFT may have an aggressive behavior, however, conservative
      surgical treatment may be successful in the long term.

PMID- 22387415
TI  - Right colectomy with simultaneous vascular reconstruction for celiac and superior
      mesenteric arterial occlusion.
AB  - INTRODUCTION: Identification of the primary feeding vessel and its removal with
      corresponding lymphatics is crucial for oncologic bowel resection for colon
      cancer. However, this notion would be challenged if we encountered abnormal
      mesenteric vascular anatomy. We report a case of colon cancer with abnormal
      mesenteric circulation, for whom we performed oncologic colectomy with vascular
      reconstruction. PRESENTATION OF CASE: A 61-year-old man presented with
      obstructing transverse colon cancer. A contrast-enhanced computed tomography (CT)
      scan showed complete occlusion at the root of the superior mesenteric artery
      (SMA) and the celiac artery (CA), with evidently dilated marginal artery (MA). An
      X-ray angiography revealed retrograde arterial blood flow originating from the
      inferior mesenteric artery (IMA) via the MA, the SMA, and to the CA. At
      laparotomy, we found remarkably dilated MA with the mid-transverse colon cancer.
      There were no other communicating vessels between the IMA and the SMA. Right
      colectomy with proper lymph node dissection was completed, following vascular
      anastomosis between the MA to the SMA. His postoperative course was uneventful. A
      postoperative CT angiography showed revascularization of the areas where the SMA
      and the CA supplied. DISCUSSION: In this patient, if the abberant mesenteric
      circulation remained unrecognized at the time of surgery, and the MA were divided
      without vascular reconstruction, severe ischemia and subsequent gangrene of large
      part of the visceral organs would have occurred. CONCLUSION: This case
      illustrates the fundamental importance of assessment for vascular anatomy in
      patients undergoing oncologic abdominal surgery which associates with division of
      major mesenteric arteries.

PMID- 22387424
TI  - Selective phosphodiesterase 3 inhibitor olprinone attenuates meconium-induced
      oxidative lung injury.
AB  - Since inflammation and oxidation play a key role in the pathophysiology of
      neonatal meconium aspiration syndrome, various anti-inflammatory drugs have been
      tested in the treatment. This study evaluated whether the phosphodiesterase (PDE)
      3 inhibitor olprinone can alleviate meconium-induced inflammation and oxidative
      lung injury. Oxygen-ventilated rabbits intratracheally received 4 ml/kg of
      meconium (25 mg/ml) or saline. Thirty minutes after meconium/saline instillation,
      meconium-instilled animals were treated by intravenous olprinone (0.2 mg/kg) or
      were left without treatment. All animals were oxygen-ventilated for an additional
      5 h. A bronchoalveolar lavage (BAL) of the left lungs was performed and
      differential leukocyte count in the sediment was estimated. The right lungs were
      used to determine lung edema by wet/dry weight ratio, as well as to detect
      oxidative damage to the lungs. In the lung tissue homogenate, total antioxidant
      status (TAS) was determined. In isolated lung mitochondria, the thiol group
      content, conjugated dienes, thiobarbituric acid-reactive substances (TBARS),
      dityrosine, lysine-lipid peroxidation products, and activity of cytochrome c
      oxidase (COX) were estimated. To evaluate the effects of meconium instillation
      and olprinone treatment on the systemic level, TBARS and TAS were determined in
      the blood plasma, as well. Meconium instillation increased the relative numbers
      of neutrophils and eosinophils in the BAL fluid, increased edema formation and
      concentrations of oxidation markers, and decreased TAS. Treatment with olprinone
      reduced the numbers of polymorphonuclears in the BAL fluid, decreased the
      formation of most oxidation markers in the lungs, reduced lung edema and
      prevented a decrease in TAS in the lung homogenate compared to non-treated
      animals. In the blood plasma, olprinone decreased TBARS and increased TAS
      compared to the non-treated group. Conclusion, the selective PDE3 inhibitor
      olprinone has shown potent antioxidative and anti-inflammatory effects in the
      meconium-induced oxidative lung injury.

PMID- 22387425
TI  - Phase-dependent locomotor activity in first-stadium nymphs of the desert locust,
      Schistocerca gregaria: effects of parental and progeny rearing density.
AB  - This study examined the effects of parental and progeny rearing density on
      locomotor activity of 1st-stadium nymphs of the desert locust, Schistocerca
      gregaria, using an actograph. Progeny obtained from solitarious (isolated-reared)
      or gregarious (crowd-reared) locusts were reared in isolation or in a group of 30
      nymphs. Crowding after hatching had a slight influence on mean activity shortly
      after the start of measurements, but no clear effect was detected until day 2,
      when maximum activity during the 6-24 h of observation was significantly higher
      than that of the nymphs kept in isolation. On the other hand, the effects of
      parental rearing density on locomotor activity manifested at all ages examined (0
      2 days old). Progeny of gregarious locusts showed consistently higher activity
      than those of solitarious locusts. In newly hatched nymphs, the effect of
      parental rearing density was explained by variation in body size at hatching, one
      of the phase-dependent characteristics. Hatchling body color was also correlated
      with locomotor activity and body weight. Similar levels of locomotor activity
      were exhibited when green, solitarious and black, gregarious nymphs were similar
      in body weight. These results suggested that parental rearing density indirectly
      influences locomotor activity in the progeny shortly after hatching by affecting
      their body size as eggs or hatchlings.

PMID- 22387426
TI  - Application of low-cost algal nitrogen source feeding in fuel ethanol production
      using high gravity sweet potato medium.
AB  - Protein-rich bloom algae biomass was employed as nitrogen source in fuel ethanol
      fermentation using high gravity sweet potato medium containing 210.0 g l(-1)
      glucose. In batch mode, the fermentation could not accomplish even in 120 h
      without any feeding of nitrogen source. While, the feeding of acid-hydrolyzed
      bloom algae powder (AHBAP) notably promoted fermentation process but untreated
      bloom algae powder (UBAP) was less effective than AHBAP. The fermentation times
      were reduced to 96, 72, and 72 h if 5.0, 10.0, and 20.0 g l(-1) AHBAP were added
      into medium, respectively, and the ethanol yields and productivities increased
      with increasing amount of feeding AHBAP. The continuous fermentations were
      performed in a three-stage reactor system. Final concentrations of ethanol up to
      103.2 and 104.3 g l(-1) with 4.4 and 5.3 g l(-1) residual glucose were obtained
      using the previously mentioned medium feeding with 20.0 and 30.0 g l(-1) AHBAP,
      at dilution rate of 0.02 h(-1). Notably, only 78.5 g l(-1) ethanol and 41.6 g l(
      1) residual glucose were obtained in the comparative test without any nitrogen
      source feeding. Amino acids analysis showed that approximately 67% of the protein
      in the algal biomass was hydrolyzed and released into the medium, serving as the
      available nitrogen nutrition for yeast growth and metabolism. Both batch and
      continuous fermentations showed similar fermentation parameters when 20.0 and
      30.0 g l(-1) AHBAP were fed, indicating that the level of available nitrogen in
      the medium should be limited, and an algal nitrogen source feeding amount higher
      than 20.0 g l(-1) did not further improve the fermentation performance.

PMID- 22387427
TI  - The mechanism of photoinhibition in vivo: re-evaluation of the roles of catalase,
      alpha-tocopherol, non-photochemical quenching, and electron transport.
AB  - Photoinhibition of photosystem II (PSII) occurs when the rate of light-induced
      inactivation (photodamage) of PSII exceeds the rate of repair of the photodamaged
      PSII. For the quantitative analysis of the mechanism of photoinhibition of PSII,
      it is essential to monitor the rate of photodamage and the rate of repair
      separately and, also, to examine the respective effects of various perturbations
      on the two processes. This strategy has allowed the re-evaluation of the results
      of previous studies of photoinhibition and has provided insight into the roles of
      factors and mechanisms that protect PSII from photoinhibition, such as catalases
      and peroxidases, which are efficient scavengers of H(2)O(2); alpha-tocopherol,
      which is an efficient scavenger of singlet oxygen; non-photochemical quenching,
      which dissipates excess light energy that has been absorbed by PSII; and the
      cyclic and non-cyclic transport of electrons. Early studies of photoinhibition
      suggested that all of these factors and mechanisms protect PSII against
      photodamage. However, re-evaluation by the strategy mentioned above has indicated
      that, rather than protecting PSII from photodamage, they stimulate protein
      synthesis, with resultant repair of PSII and mitigation of photoinhibition. This
      article is part of a Special Issue entitled: Photosynthesis Research for
      Sustainability: from Natural to Artificial.

PMID- 22387428
TI  - A new training procedure for studying discrimination learning in fish.
AB  - The study of animal cognition and its neurobiological bases often requires the
      adoption of associative learning procedures. Though fish are increasingly being
      used as a model system in behavioral neuroscience, the availability of adequate
      learning protocols can be a limiting factor in this field of research. This study
      describes a novel training procedure to explore visual discrimination in fish.
      Subjects were singly housed in rectangular tanks. At intervals, two stimuli were
      introduced at opposite ends of the tank and food was delivered near the stimulus
      to be reinforced. Time spent near positive stimulus in probe trials was taken as
      a measure of discrimination performance. To validate the method, we replicated
      two published studies that used operant conditioning to investigate the
      mechanisms of numerical discrimination in mosquitofish. Our data indicate a
      complete overlap of the results obtained using the two different methods. The
      pros and cons of the new procedure are discussed in respect of traditional
      associative learning paradigms.

PMID- 22387429
TI  - Wavelet analysis demonstrates no abnormality in contralateral suppression of
      otoacoustic emissions in tinnitus patients.
AB  - The efferent auditory system is thought to play a role in the origin of tinnitus.
      Part of this system can be tested in humans with contralateral suppression of
      otoacoustic emissions. Stimulation of the medial olivocochlear efferent system is
      responsible for this reduction of otoacoustic emissions after contralateral
      acoustic stimulation. Previous research on patients with tinnitus showed
      inconclusive results. With wavelet analysis both time and frequency information
      of the emission can be analysed and compared. Contralateral suppression of
      otoacoustic emissions was therefore measured in tinnitus patients (n = 26) and
      normal subjects (n = 37) and analysed using wavelets. No significant difference
      in suppression was found between the tinnitus patients and the control group.

PMID- 22387430
TI  - The joint association of eating frequency and diet quality with colorectal cancer
      risk in the Health Professionals Follow-up Study.
AB  - The results of most case-control studies have suggested a positive association
      between eating frequency and colorectal cancer risk. Because no prospective
      cohort studies have done so to date, the authors prospectively examined this
      association. In 1992, eating frequency was assessed in a cohort of 34,968 US men
      in the Health Professionals Follow-up Study. Cox proportional hazards regression
      models were used to estimate relative risks and 95% confidence intervals for
      various levels of eating frequency. Effect modifications by overall dietary
      quality (assessed using the Diet Approaches to Stop Hypertension score) and by
      factors that influence insulin resistance were further assessed. Between 1992 and
      2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing
      the highest eating frequency category (5-8 times/day) with the reference category
      (3 times/day), the authors found no evidence of an increased risk of colorectal
      cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26)
      or colon cancer (multivariate relative risk = 0.78, 95% confidence interval:
      0.49, 1.25). There was an implied inverse association with eating frequency among
      participants who had healthier diets (high Diet Approaches to Stop Hypertension
      score; P for interaction = 0.01), especially among men in the high-insulin
      sensitivity group (body mass index (weight (kg)/height (m)(2)) <25, >=2 cups of
      coffee/day, and more physical activity; P for interaction < 0.01, P for trend =
      0.01). There was an implied protective association between increased eating
      frequency of healthy meals and colorectal cancer risk and in men with factors
      associated with higher insulin sensitivity.

PMID- 22387431
TI  - The role of sulfatide lipid domains in the membrane pore-forming activity of
      cobra cardiotoxin.
AB  - Cobra CTX A3, the major cardiotoxin (CTX) from Naja atra, is a cytotoxic, basic
      beta-sheet polypeptide that is known to induce a transient membrane leakage of
      cardiomyocytes through a sulfatide-dependent CTX membrane pore formation and
      internalization mechanism. The molecular specificity of CTX A3-sulfatide
      interaction at atomic levels has also been shown by both nuclear magnetic
      resonance (NMR) and X-ray diffraction techniques to reveal a role of CTX-induced
      sulfatide conformational changes for CTX A3 binding and dimer formation. In this
      study, we investigate the role of sulfatide lipid domains in CTX pore formation
      by various biophysical methods, including fluorescence imaging and atomic force
      microscopy, and suggest an important role of liquid-disordered (ld) and solid
      ordered (so) phase boundary in lipid domains to facilitate the process.
      Fluorescence spectroscopic studies on the kinetics of membrane leakage and CTX
      oligomerization further reveal that, although most CTXs can oligomerize on
      membranes, only a small fraction of CTXs oligomerizations form leakage pores. We
      therefore suggest that CTX binding at the boundary between the so and so/ld phase
      coexistence sulfatide lipid domains could form effective pores to significantly
      enhance the CTX-induced membrane leakage of sulfatide-containing
      phosphatidylcholine vesicles. The model is consistent with our earlier
      observations that CTX may penetrate and lyse the bilayers into small aggregates
      at a lipid/protein molar ratio of about 20 in the ripple P(beta)' phase of
      phosphatidylcholine bilayers and suggest a novel mechanism for the synergistic
      action of cobra secretary phospholipase A2 and CTXs.

PMID- 22387432
TI  - Comparative molecular dynamics simulations of the antimicrobial peptide CM15 in
      model lipid bilayers.
AB  - We report altogether 3-MUs molecular dynamics (MD) simulations of the
      antimicrobial peptide CM15 to systematically investigate its interaction with two
      model lipid bilayers, pure POPC and mixed POPG:POPC (1:2). Starting with either
      an alpha-helical or a random-coil conformation, CM15 is found to insert into both
      bilayers. Peptide-lipid interaction is stronger with the anionic POPG:POPC than
      the zwitterionic POPC, which is largely attributed to the electrostatic
      attraction between CM15 and the negatively charged POPG. Simulations initiated
      with CM15 as a random coil allowed us to study peptide folding at the lipid-water
      interface. Interestingly, CM15 folding appears to be faster in POPC than
      POPG:POPC, which may be explained by a lower activation energy barrier of
      structural rearrangement in the former system. Our data also suggest that
      compared with the random-coil conformation, CM15 in a pre-folded alpha-helix has
      significantly reduced interactions with the lipids, indicating that peptide
      initial structures may bias the simulation results considerably on the 100-ns
      timescale. The implications of this result should be considered when preparing
      and interpreting future AMP simulations.

PMID- 22387433
TI  - Minor structural modifications to alchemix influence mechanism of action and
      pharmacological activity.
AB  - Alchemix is an exemplar of a class of anthraquinone with efficacy against
      multidrug resistant tumours. We have explored further the mechanism of action of
      alchemix and investigated the effect of extending its side arm bearing the
      alkylating functionality with regard to DNA binding and activity against
      multidrug resistant cancer cells. Increasing the distance between the
      intercalating chromophore and the alkylating functionality of ICT2901 (propyl),
      ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation
      sites, more potent topoisomerase II inhibition and generated more apoptotic and
      necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly,
      alchemix, the compound with the shortest distance between its intercalative
      chromophore and alkylating functionality (ethyl), did not conform to this SAR. A
      different toxicity pattern against DNA repair defective CHO cell lines as well as
      arrest of cells in G1 supports a somewhat distinct mode of action by alchemix
      compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated
      greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than
      wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series
      has led to significant changes to the stability of DNA-compound complexes and
      cellular activity. Given that the failure of chemotherapy in the clinic is often
      associated with MDR, the results of both alchemix and ICT2901 represent important
      advances towards improved therapies.

PMID- 22387435
TI  - Letter from the editor.

PMID- 22387436
TI  - An investigation into the factors affecting patient selection of chronic low back
      management methods, with particular reference to non-utilization of the
      complimentary therapies, in the United Kingdom.
AB  - Chronic low back pain (CLBP) is an increasingly common, persistent and costly
      problem. There is evidence to suggest that some sufferers benefit more from
      methods still considered 'complimentary' in the UK, than from the conventional
      management methods, which continue to be offered as standard care under the
      British National Health System (NHS). Despite this evidence, relatively few CLBP
      sufferers in the UK utilize these 'complimentary' therapies. This investigation
      set out to evaluate what factors affect utilization and asks why people do not
      use complimentary therapies (CTs) for CLBP, as this has not been asked before.
      One hundred and fifty subjects completed self-reporting questionnaires, which
      asked about knowledge, health care beliefs and other possible influencing
      factors. The three groups comprised 50 CLBP sufferers using both private and
      National Health Service (NHS) funded outpatient conventional management methods,
      50 CLBP sufferers using private CT management methods, and 50 'healthy' non-user
      subjects. Sixty-four per cent of conventional patients had not used CTs. The most
      significant barriers to the utilization of CTs appeared to be lack of knowledge
      and lower socio-economic group (SEG). Gender may affect selection.

PMID- 22387434
TI  - Low resolution structural characterization of the Hsp70-interacting protein - Hip
      - from Leishmania braziliensis emphasizes its high asymmetry.
AB  - The Hsp70 is an essential molecular chaperone in protein metabolism since it acts
      as a pivot with other molecular chaperone families. Several co-chaperones act as
      regulators of the Hsp70 action cycle, as for instance Hip (Hsp70-interacting
      protein). Hip is a tetratricopeptide repeat protein (TPR) that interacts with the
      ATPase domain in the Hsp70-ADP state, stabilizing it and preventing substrate
      dissociation. Molecular chaperones from protozoans, which can cause some
      neglected diseases, are poorly studied in terms of structure and function. Here,
      we investigated the structural features of Hip from the protozoa Leishmania
      braziliensis (LbHip), one of the causative agents of the leishmaniasis disease.
      LbHip was heterologously expressed and purified in the folded state, as attested
      by circular dichroism and intrinsic fluorescence emission techniques. LbHip forms
      an elongated dimer, as observed by analytical gel filtration chromatography,
      analytical ultracentrifugation and small angle X-ray scattering (SAXS). With the
      SAXS data a low resolution model was reconstructed, which shed light on the
      structure of this protein, emphasizing its elongated shape and suggesting its
      domain organization. We also investigated the chemical-induced unfolding behavior
      of LbHip and two transitions were observed. The first transition was related to
      the unfolding of the TPR domain of each protomer and the second transition of the
      dimer dissociation. Altogether, LbHip presents a similar structure to mammalian
      Hip, despite their low level of conservation, suggesting that this class of
      eukaryotic protein may use a similar mechanism of action.

PMID- 22387437
TI  - Diagnosis of avascular necrosis of the hip in asymptomatic HIV-infected patients:
      Clinical correlation of physical examination with magnetic resonance imaging.
AB  - OBJECTIVE: To determine if physical examination can identify avascular necrosis
      of the hip (AVN) in asymptomatic HIV-infected patients. DESIGN: Prospective,
      blinded population studyResults: Ten of the 176 patients were positive for AVN by
      MRI. Four subjects had unilateral disease and six had bilateral disease. Five
      hips (1.4%) in four patients were indeterminate. We evaluated physical
      examination maneuvers both singly and in combination. Tests done singly generally
      provided a higher degree of specificity (67-92%) but sensitivities were lower (0
      50%) with all p-values >=0.08. Positive predictive values based on physical exam,
      were <17% and negative predictive values were >90% for any single test. Combining
      all tests gave a high sensitivity (88%) and negative predictive value (98%), but
      low specificity (34%) and positive predictive value (6%) with p = 0.10. Only two
      of 16 hips with positive MRI findings showed no abnormalities when all tests were
      combinedConclusions: This study establishes the limited usefulness of a detailed
      physical examination of the hip early in the course of AVN. Patients who test
      negative on physical exam are unlikely to have AVN positive by MRI. Positive
      findings on physical examination of the hip may help identify patients who need
      further evaluation by MRI based on overall clinical suspicion.

PMID- 22387438
TI  - Topiramate for phantom limb pain in an upper limb amputee: A case report.
AB  - OBJECTIVE: To increase the awareness of topiramate as a phantom limb pain
      treatment. SETTING: Outpatient rehabilitation office in an urban academic center.
      PATIENT: 34-year-old white female who suffered a traumatic right upper limb
      amputation. INTERVENTION: Oral topiramate at an initial dosage of 100 milligrams
      per day increased to 200 milligrams per day. RESULTS AND CONCLUSION: After
      failure of multiple medications traditionally used to control phantom pain, the
      patient described significant relief with the use of oral topiramate. The authors
      suggest topiramate as an alternative approach to phantom limb pain treatment.

PMID- 22387439
TI  - Injuries in artistic gymnastic elite adolescent male and female athletes.
AB  - OBJECTIVES: The purpose of this study was to record the incidence of Sport
      Injuries (acute and overuse syndromes) in Greek artistic gymnasts in relation to
      sex, age, event and exercise phase. METHODS: 187 Greek elite artistic gymnastic
      athletes (100 male and 87 female athletes) participating in Greek artistic
      gymnastic championship involving all age-related categories, were observed on a
      weekly basis for a year. The athletes consisted of the pre-national team that was
      chosen to prepare for the next Olympic games. RESULTS: 147 (61.5%)acute injuries
      and 93 (38.5%) overuse syndromes were recorded. The most common anatomical
      location of injury was the ankle (110 cases, 46%), followed by the knee (63
      cases, 26.2%). According to the results, the rate which involved mild injuries
      was 26.8% (64 cases, 34 males, 30 females) moderate injuries was 44% (106 cases,
      59 males, 48 females), major injuries was 29% (70 cases, 38 males, 31 females).
      For the total sport injuries recorded, the injury incidence on the "floor" and
      especially during "landing phase", were statistically significant. CONCLUSIONS:
      Artistic gymnastics predisposes to acute injuries, by its nature, but up to 70%
      are mild and moderate. Special attention needs to be given during "floor
      exercises", especially on landing phase.

PMID- 22387440
TI  - The relationship between lower extremity injury and the hip abductor to extensor
      strength ratio in collegiate athletes.
AB  - OBJECTIVE: To determine the relationship of previous lower extremity injury and
      the measured ratio of hip abduction to extension strength in collegiate athletes.
      DESIGN: Cohort study of college athletes at time of pre-participation screening
      physical. SETTING: An NCAA Division I college. PARTICIPANTS: Two hundred and
      thirty-six college athletes from a NCAA Division I school (162) males and (74)
      females. MAIN OUTCOME MEASURES: The ratio of maximal hip abduction to extension
      strength was calculated, following raw data collection with a specially designed
      dynamometer anchoring station. Injury to the lower extremities, in the past year,
      was recorded via personal interview at the time of screening and verified by
      review of previous injury records. RESULTS: A significant difference in the ratio
      of hip abduction to extension strength was noted on the left lower extremity of
      athletes with reported lower extremity (LE) injury compared to those without
      injury. Upon further review of data, hip extension weakness appears to be the
      likely cause of this difference. CONCLUSION: Athletes with reported lower
      extremity injury demonstrated a significant residual difference in the ratio of
      hip abduction to extension strength. This may be the result of injury related
      muscle weakness, altered muscle firing patterns, central inhibition or unknown
      compensatory strategies which all may be risk factors for recurrent injury.
      Further research is underway to identify the cause/effect relationship of this
      finding. CLINICAL RELEVANCE: This study may advance our understanding of
      potential compensatory strategies about the hip which theoretically may result
      from previous lower extremity injury or injuries which are incompletely
      rehabilitated. Additionally, this study provides some reasoning to support the
      screening of hip strength during the pre-participation physical, as it may be an
      important factor to prevent recurrent injury.

PMID- 22387441
TI  - Criterion validity study of lumbar goniometers BROM II and EDI-320 for range of
      motion of lumbar flexion of low back pain patients.
AB  - PURPOSE: The purpose was to estimate the criterion validity of the Back Range of
      Motion (BROM II) and Electronic Digital Inclinometer (EDI-320) devices. METHODS.
      This study compared the range of motion measurements of low back pain (LBP)
      patients taken with the BROM II and EDI-320 with measurements using the double
      inclinometer (DI) method as the gold standard. Forty subjects with LBP
      volunteered for the study. The subjects were asked to do three forward flexion
      movements. A measurement was taken with each of the three different devices for
      each movement. RESULTS: The BROM II demonstrated good linear relationship
      (Pearson r = 0.78; 95% CI: 0.78-0.94) and the EDI-320 very good linear
      relationship (Pearson r = 0.88; 95% CI: 0.62-0.89) with the gold standard, the
      DI. CONCLUSIONS: The Pearson correlation value indicates good validity of the EDI
      320 in our sample of LBP patients. Although a good correlation was established
      for the BROM II, the significant difference of the mean ROM reported for this
      instrument compared to the gold standard data suggests that the BROM II actually
      measures ROM differently. Our results suggest that the EDI 320 is clinically
      useful in providing objective and valid data for outcome measures in a population
      with LBP. More research is needed on the BROM II before we can make final
      conclusion on its use in clinical settings as an outcome measure.

PMID- 22387442
TI  - Measuring reliability of effort in functional capacity evaluations using digital
      video analysis.
AB  - Functional capacity evaluations (FCE) are utilized to evaluate the physical
      abilities of workers to perform the specific demands of a job. FCEs are being
      used increasingly by insurers, employers, health care providers and attorneys as
      the basis to make decisions regarding workplace supports, vocational
      rehabilitation, disability determination, and litigation. These factors require
      that FCEs must have objectivity, reliability, validity and defensibility. One of
      the key elements in the usefulness of an FCE is a measure of the level of effort
      given by the individual being tested. This study investigated determinants of an
      FCE that identified corresponding level of effort. Thirty-five healthy adults
      participated in a study to investigate whether computerized video movement
      analysis was an effective tool to determine consistency of effort during lifting
      (floor to waist and waist to overhead) and squatting activities of an FCE. Video
      data were examined using computerized analysis of each movement. The association
      between six factors identified from the video analysis and the distinction
      between real and intentionally sub-maximal efforts was analyzed. Terminal
      acceleration, mean velocity, and peak velocity were consistently, significantly
      correlated with consistency of effort in all three FCE activities. Computerized
      analyses of video taped FCE activities can identify factors associated with
      consistency of effort.

PMID- 22387443
TI  - Cardiovascular armamentarium in a patient with bronchopulmonary fistula.

PMID- 22387444
TI  - 'To CT or not to CT? That is the question': outcome surrogates for surveillance
      in childhood cystic fibrosis.

PMID- 22387445
TI  - Combined Haemophilus influenzae respiratory infection and allergic airways
      disease drives chronic infection and features of neutrophilic asthma.
AB  - BACKGROUND: 20-30% of patients with asthma have neutrophilic airway inflammation
      and reduced responsiveness to steroid therapy. They often have chronic airway
      bacterial colonisation and Haemophilus influenzae is one of the most commonly
      isolated bacteria. The relationship between chronic airway colonisation and the
      development of steroid-resistant neutrophilic asthma is unclear. OBJECTIVES: To
      investigate the relationship between H influenzae respiratory infection and
      neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced
      allergic airways disease. METHODS: BALB/c mice were intratracheally infected with
      H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally
      challenged (day 12-15) with OVA. Treatment groups were administered dexamethasone
      intranasally during OVA challenge. Infection, allergic airways disease, steroid
      sensitivity and immune responses were assessed (days 11, 16 and 21). RESULTS: The
      combination of H influenzae infection and allergic airways disease resulted in
      chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31
      days after infection). Neutrophilic allergic airways disease and T helper 17 cell
      development were induced, which did not require active infection. Importantly,
      all features of neutrophilic allergic airways disease were steroid resistant.
      Toll-like receptor 4 expression and activation of phagocytes was reduced, but
      most significantly the influx and/or development of phagocytosing neutrophils and
      macrophages into the airways was inhibited. CONCLUSIONS: The combination of
      infection and allergic airways disease promotes bacterial persistence, leading to
      the development of a phenotype similar to steroid-resistant neutrophilic asthma
      and which may result from dysfunction in innate immune cells. This indicates that
      targeting bacterial infection in steroid-resistant asthma may have therapeutic
      benefit.

PMID- 22387449
TI  - Acid-base balance during social interactions in rainbow trout (Oncorhynchus
      mykiss).
AB  - Socially subordinate rainbow trout (Oncorhynchus mykiss) experience chronic
      stress that impacts upon a variety of physiological functions, including Na(+)
      regulation. Owing to the tight coupling between Na(+) and Cl(-) uptake and,
      respectively, H(+) and HCO(3)(-) loss at the gill, ionoregulatory changes
      associated with social status may affect acid-base regulation. The present study
      assessed the responses of dominant, subordinate and control trout to hypercapnia
      (1% CO(2)) to test this hypothesis. Social status appeared to impact net acid
      excretion (J(net)H(+)) as subordinate individuals failed to increase net acid
      flux in response to hypercapnia. However, blood acid-base status was found to be
      unaffected by social status before or during hypercapnic exposure, indicating
      that subordinate fish were as effective as dominant or control trout in achieving
      compensation for the acid-base disturbance induced by hypercapnic exposure.
      Compensation in all groups involved decreasing Cl(-) uptake in response to
      hypercapnia. The branchial activities of both Na(+),K(+)-ATPase (NKA) and V-type
      H(+)-ATPase were affected by social interactions and/or exposure to hypercapnia.
      Branchial NKA activity was higher but V-ATPase activity was lower in control fish
      than in dominant or subordinate trout. In addition, control and subordinate but
      not dominant trout exposed to 24h of hypercapnia exhibited significantly higher
      branchial V-ATPase activity than fish maintained in normocapnia. Collectively,
      the data suggest that subordinate trout are able to regulate blood pH during a
      respiratory acidosis.

PMID- 22387450
TI  - Urinary corticosterone metabolites and chytridiomycosis disease prevalence in a
      free-living population of male Stony Creek frogs (Litoria wilcoxii).
AB  - The emerging amphibian disease chytridiomycosis, which is caused by the fungal
      pathogen (Batrachochytrium dendrobatidis, Bd), has caused mass mortalities of
      native amphibian populations globally. There have been no previous studies on the
      relationships between stress hormones in free-living amphibians and Bd
      infections. In this study, we measured urinary corticosterone metabolite
      concentrations and Bd infections within free-living populations of male Stony
      Creek frog (Litoria wilcoxii) in Queensland, Australia. Prevalence of Bd
      zoospores from frog skin swabs was quantified using a real-time quantitative PCR
      technique. A urinary corticosterone enzyme-immunoassay (EIA) was validated using
      adrenocorticotropic hormone (ACTH) challenge. Urinary corticosterone
      concentrations of male frogs increased within 1-2 days after ACTH challenge and
      returned to baseline levels within 3 days post-ACTH injection. None of the frogs
      showed any rise in urinary corticosterone after saline injections. Individual
      male frogs showed either low or high baseline corticosterone concentrations. Male
      frogs identified as positive for Bd infection had significantly higher baseline
      urinary corticosterone concentrations in comparison to Bd negative male frogs.
      Urinary corticosterone EIA provides a reliable indication of stress in this frog
      species and this non-invasive physiological tool can be used to further assess
      the dynamics of Bd infections and physiological stress responses in other native
      amphibians.

PMID- 22387451
TI  - Phase II trial of imatinib mesylate in patients with recurrent platinum- and
      taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or
      fallopian tube.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of imatinib mesylate in
      patients with recurrent low-grade serous carcinoma (LGSC) of the ovary,
      peritoneum, or fallopian tube. METHODS: This open-label, single-institution phase
      II trial enrolled patients with platinum-resistant LGSC who had measurable
      disease, had received up to 4 platinum- and/or taxane-containing chemotherapy
      regimens, and had been previously screened for at least one imatinib targeted
      biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-beta, or bcr
      abl). Imatinib (600 mg) was administered daily for one 6-week course and
      continued in the absence of toxicity and disease progression. RESULTS: Thirteen
      patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for
      response. A total of 17 courses were administered (median, 1 course; range, 1-5
      courses). Complete or partial responses were not observed. One patient had stable
      disease for 7.3 months. c-Kit, bcr-abl, or PDGFR-beta were present in 48%, 77%,
      and 100% of patients, respectively. No correlation between best response (stable
      disease) and the presence of imatinib-targeted biomarkers was observed. Adverse
      events included grade 3 skin rash in one patient leading to discontinuation of
      the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients
      leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue
      (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included
      skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed.
      The median progression-free survival time was 1.3 months (95% CI, 1.27, 1.40
      months), and the median overall survival time was 14.9 months (95% CI, 11.0, 18.9
      months). CONCLUSION: Imatinib is well-tolerated but has no activity in patients
      with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian
      tube.

PMID- 22387453
TI  - Enhancement of immune response towards non-lipidized Borrelia burgdorferi
      recombinant OspC antigen by binding onto the surface of metallochelating
      nanoliposomes with entrapped lipophilic derivatives of norAbuMDP.
AB  - Lyme disease caused by spirochete Borrelia burgdorferi sensu lato, is a tick-born
      illness. If the infection is not eliminated by the host immune system and/or
      antibiotics, it may further disseminate and cause severe chronic complications.
      The immune response to Borrelia is mediated by phagocytic cells and by Borrelia
      specific complement-activating antibodies associated with Th1 cell activation. A
      new experimental vaccine was constructed using non-lipidized form of recombinant
      B. burgdorferi s.s. OspC protein was anchored by metallochelating bond onto the
      surface of nanoliposomes containing novel nonpyrogenic lipophilized norAbuMDP
      analogues denoted MT05 and MT06. After i.d. immunization, the experimental
      vaccines surpassed Alum with respect to OspC-specific titers of IgG2a, IgG2b
      isotypes when MT06 was used and IgG3, IgM isotypes when MT05 was used. Both
      adjuvants exerted a high adjuvant effect comparable or better than MDP and proved
      themselves as nonpyrogenic.

PMID- 22387454
TI  - Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age
      related macular degeneration in Finnish population.
AB  - Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid,
      and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk
      factor for age-related macular degeneration (AMD). We, therefore, examined
      associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and
      Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of
      advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and
      ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having
      exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were
      diagnosed by fundus photographs and fluorescein angiography. The control group
      (no signs of AMD in fundus photographs) consisted of 55 men and 111 women.
      Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of
      the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly
      associated (p=0.0471) with AMD status when using a permutation procedure that
      controlled for the number of tested genotypes and genetic models. Odds ratio (OR)
      for the association was 1.699 (95% CI 1.192-2.423). The SNP consists of C/T
      alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%.
      Distribution of proportion of cases/controls between alleles revealed an additive
      genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel
      candidate for AMD genetic risk factor in Finnish population.

PMID- 22387455
TI  - The effects of prepulse inhibition timing on the startle reflex and reaction
      time.
AB  - A loud acoustic stimulus has been shown to provoke a reflexive startle response
      and accelerate simple reaction times. However, an auditory prepulse presented in
      advance of a startling stimulus can reduce the effect of the startling stimulus.
      The current study examined the effect of the timing of the prepulse on startle
      induced reaction times and the startle reflex. The task was to perform a 30
      degrees  arm extension movement in response to a visual "go" stimulus. On
      selected trials, an auditory prepulse (80dB) was presented either 100ms, 500ms or
      1000ms prior to the "go" signal. In addition, an auditory startling stimulus
      (124dB) was presented in conjunction with the "go" signal on some trials. Our
      results indicated that an auditory prepulse presented 100ms, and to a lesser
      extent 500ms, significantly decreased the amplitude of the startle reflex;
      however, the reaction time acceleration associated with the startling acoustic
      stimulus (SAS) was unaffected. The differential effect of the prepulse on the
      startle reflex and reaction time acceleration confirm different neural pathways
      for these effects while the differential effect of the prepulse on the control
      and startle RTs suggest different mechanisms for movement initiation.

PMID- 22387456
TI  - Interferon beta modulates major histocompatibility complex class I (MHC I) and
      CD3-zeta expression in PC12 cells.
AB  - It has been demonstrated that the major histocompatibility complex of class I
      (MHC I) up regulation by exogenous treatment with interferon beta (IFNbeta)
      influences the glial reaction and synaptic elimination process. Therefore, the
      present study aimed to investigate the effects of IFNbeta treatment on the
      expression of MHC I, CD3-zeta (a subunit of MHC I receptor) and synaptic
      formation in PC12 cells, an in vitro model for studying the synaptic
      formation/elimination process. For this purpose, established cultures were
      subjected to IFNbeta (500 and 1000IU/ml) treatment for 5, 10 and 15 days. The
      cells were then fixed and processed for immunocytochemistry with antisera against
      MHC I (OX18), CD3-zeta and synaptophysin. The results were compared with control
      cultures only treated with basal medium. IFNbeta (500IU/ml) modulated the MHC I
      expression in PC12 cells, especially after 10 days of treatment. In this sense,
      IFNbeta induced MHC I as well as CD3-zeta up regulation. It was observed that the
      highest dose caused culture degeneration. Interestingly, differential regulation
      of MHC I was paralleled by enhancement in synaptic network remodeling.
      Altogether, the present data indicate that PC12 cells may be used as an in vitro
      model for studying MHC I modulation and synaptic plasticity. It also reinforced
      the role of IFNbeta on the synaptic elimination process.

PMID- 22387457
TI  - A tetrahedral coordination of Zinc during transmembrane transport by P-type
      Zn(2+)-ATPases.
AB  - Zn(2+) is an essential transition metal required in trace amounts by all living
      organisms. However, metal excess is cytotoxic and leads to cell damage. Cells
      rely on transmembrane transporters, with the assistance of other proteins, to
      establish and maintain Zn(2+) homeostasis. Metal coordination during transport is
      key to specific transport and unidirectional translocation without the backward
      release of free metal. The coordination details of Zn(2+) at the transmembrane
      metal binding site responsible for transport have now been established.
      Escherichia coli ZntA is a well-characterized Zn(2+)-ATPase responsible for
      intracellular Zn(2+) efflux. A truncated form of the protein lacking regulatory
      metal sites and retaining the transport site was constructed. Metrical parameters
      of the metal-ligand coordination geometry for the zinc bound isolated form were
      characterized using x-ray absorption spectroscopy (XAS). Our data support a
      nearest neighbor ligand environment of (O/N)(2)S(2) that is compatible with the
      proposed invariant metal coordinating residues present in the transmembrane
      region. This ligand identification and the calculated bond lengths support a
      tetrahedral coordination geometry for Zn(2+) bound to the TM-MBS of P-type ATPase
      transporters.

PMID- 22387458
TI  - Adaptation to low body temperature influences pulmonary surfactant composition
      thereby increasing fluidity while maintaining appropriately ordered membrane
      structure and surface activity.
AB  - The interfacial surface tension of the lung is regulated by phospholipid-rich
      pulmonary surfactant films. Small changes in temperature affect surfactant
      structure and function in vitro. We compared the compositional, thermodynamic and
      functional properties of surfactant from hibernating and summer-active 13-lined
      ground squirrels (Ictidomys tridecemlineatus) with porcine surfactant to
      understand structure-function relationships in surfactant membranes and films.
      Hibernating squirrels had more surfactant large aggregates with more fluid
      monounsaturated molecular species than summer-active animals. The latter had more
      unsaturated species than porcine surfactant. Cold-adapted surfactant membranes
      displayed gel-to-fluid transitions at lower phase transition temperatures with
      reduced enthalpy. Both hibernating and summer-active squirrel surfactants
      exhibited lower enthalpy than porcine surfactant. LAURDAN fluorescence and DPH
      anisotropy revealed that surfactant bilayers from both groups of squirrels
      possessed similar ordered phase characteristics at low temperatures. While ground
      squirrel surfactants functioned well during dynamic cycling at 3, 25, and 37
      degrees C, porcine surfactant demonstrated poorer activity at 3 degrees C but was
      superior at 37 degrees C. Consequently the surfactant composition of ground
      squirrels confers a greater thermal flexibility relative to homeothermic mammals,
      while retaining tight lipid packing at low body temperatures. This may represent
      the most critical feature contributing to sustained stability of the respiratory
      interface at low lung volumes. Thus, while less effective than porcine surfactant
      at 37 degrees C, summer-active surfactant functions adequately at both 37 degrees
      C and 3 degrees C allowing these animals to enter hibernation. Here further
      compositional alterations occur which improve function at low temperatures by
      maintaining adequate stability at low lung volumes and when temperature increases
      during arousal from hibernation.

PMID- 22387459
TI  - Estimation of the subunit stoichiometry of the membrane-associated daptomycin
      oligomer by FRET.
AB  - Daptomycin is a lipopeptide antibiotic that kills Gram-positive bacteria by
      depolarizing their cell membranes. This antibacterial action of daptomycin is
      correlated with the formation of membrane-associated oligomers. We here examine
      the number of subunits contained in one oligomer using fluorescence resonance
      energy transfer (FRET). The results suggest that the oligomer contains
      approximately 6 to 7 subunits, or possibly twice this number if it spans both
      membrane monolayers.

PMID- 22387460
TI  - Indole prevents Escherichia coli cell division by modulating membrane potential.
AB  - Indole is a bacterial signalling molecule that blocks E. coli cell division at
      concentrations of 3-5 mM. We have shown that indole is a proton ionophore and
      that this activity is key to the inhibition of division. By reducing the
      electrochemical potential across the cytoplasmic membrane of E. coli, indole
      deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a
      prerequisite for division. This is the first example of a natural ionophore
      regulating a key biological process. Our findings have implications for our
      understanding of membrane biology, bacterial cell cycle control and potentially
      for the design of antibiotics that target the cell membrane.

PMID- 22387461
TI  - Novel therapeutic approaches to post-infarction remodelling.
AB  - Adverse cardiac remodelling is a major cause of morbidity and mortality following
      acute myocardial infarction (MI). Mechanical and neurohumoral factors involved in
      structural and molecular post-infarction remodelling were important targets in
      research and treatment for years. More recently, therapeutic strategies that
      address myocardial regeneration and pathophysiological mechanisms of infarct
      wound healing appear to be useful novel tools to prevent progressive ventricular
      dilation, functional deterioration, life-threatening arrhythmia, and heart
      failure. This review provides an overview of future and emerging therapies for
      cardiac wound healing and remodelling after MI.

PMID- 22387462
TI  - Traditional Chinese medicine research in the post-genomic era: good practice,
      priorities, challenges and opportunities.
AB  - BACKGROUND AND AIMS: GP-TCM is the 1st EU-funded Coordination Action consortium
      dedicated to traditional Chinese medicine (TCM) research. This paper aims to
      summarise the objectives, structure and activities of the consortium and
      introduces the position of the consortium regarding good practice, priorities,
      challenges and opportunities in TCM research. Serving as the introductory paper
      for the GP-TCM Journal of Ethnopharmacology special issue, this paper describes
      the roadmap of this special issue and reports how the main outputs of the ten GP
      TCM work packages are integrated, and have led to consortium-wide conclusions.
      MATERIALS AND METHODS: Literature studies, opinion polls and discussions among
      consortium members and stakeholders. RESULTS: By January 2012, through 3 years of
      team building, the GP-TCM consortium had grown into a large collaborative network
      involving ~200 scientists from 24 countries and 107 institutions. Consortium
      members had worked closely to address good practice issues related to various
      aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of
      this Journal of Ethnopharmacology special issue, leading to state-of-the-art
      reports, guidelines and consensus on the application of omics technologies in TCM
      research. In addition, through an online survey open to GP-TCM members and non
      members, we polled opinions on grand priorities, challenges and opportunities in
      TCM research. Based on the poll, although consortium members and non-members had
      diverse opinions on the major challenges in the field, both groups agreed that
      high-quality efficacy/effectiveness and mechanistic studies are grand priorities
      and that the TCM legacy in general and its management of chronic diseases in
      particular represent grand opportunities. Consortium members cast their votes of
      confidence in omics and systems biology approaches to TCM research and believed
      that quality and pharmacovigilance of TCM products are not only grand priorities,
      but also grand challenges. Non-members, however, gave priority to integrative
      medicine, concerned on the impact of regulation of TCM practitioners and
      emphasised intersectoral collaborations in funding TCM research, especially
      clinical trials. CONCLUSIONS: The GP-TCM consortium made great efforts to address
      some fundamental issues in TCM research, including developing guidelines, as well
      as identifying priorities, challenges and opportunities. These consortium
      guidelines and consensus will need dissemination, validation and further
      development through continued interregional, interdisciplinary and intersectoral
      collaborations. To promote this, a new consortium, known as the GP-TCM Research
      Association, is being established to succeed the 3-year fixed term FP7 GP-TCM
      consortium and will be officially launched at the Final GP-TCM Congress in
      Leiden, the Netherlands, in April 2012.

PMID- 22387463
TI  - Detection and imaging of the free radical DNA in cells--site-specific radical
      formation induced by Fenton chemistry and its repair in cellular DNA as seen by
      electron spin resonance, immuno-spin trapping and confocal microscopy.
AB  - Oxidative stress-related damage to the DNA macromolecule produces lesions that
      are implicated in various diseases. To understand damage to DNA, it is important
      to study the free radical reactions causing the damage. Measurement of DNA damage
      has been a matter of debate as most of the available methods measure the end
      product of a sequence of events and provide limited information on the initial
      free radical formation. We report a measurement of free radical damage in DNA
      induced by a Cu(II)-H(2)O(2) oxidizing system using immuno-spin trapping
      supplemented with electron paramagnetic resonance. In this investigation, the
      short-lived radical generated is trapped by the spin trap 5,5-dimethyl-1
      pyrroline N-oxide (DMPO) immediately upon formation. The DMPO adduct formed is
      initially electron paramagnetic resonance active, but is subsequently oxidized to
      the stable nitrone adduct, which can be detected and visualized by immuno-spin
      trapping and has the potential to be further characterized by other analytical
      techniques. The radical was found to be located on the 2'-deoxyadenosine (dAdo)
      moiety of DNA. The nitrone adduct was repaired on a time scale consistent with
      DNA repair. In vivo experiments for the purpose of detecting DMPO-DNA nitrone
      adducts should be conducted over a range of time in order to avoid missing
      adducts due to the repair processes.

PMID- 22387465
TI  - Identification of a region in the N-terminus of Escherichia coli Lon that affects
      ATPase, substrate translocation and proteolytic activity.
AB  - Lon, also known as protease La, is an AAA+ protease machine that contains the
      ATPase and proteolytic domain within each enzyme subunit. Three truncated
      Escherichia coli Lon (ELon) mutants were generated based on a previous limited
      tryptic digestion result and hydrogen-deuterium exchange mass spectrometry
      analyses performed in this study. Using methods developed for characterizing wild
      type (WT) Lon, we compared the ATPase, ATP-dependent protein degradation and ATP
      dependent peptidase activities. With the exception of not degrading a putative
      structured substrate known as CcrM (cell-cycle-regulated DNA methyltransferase),
      the mutant lacking the first 239 residues behaved like WT ELon. Comparing the
      activity data of WT and ELon mutants reveals that the first 239 residues are not
      needed for minimal enzyme catalysis. The mutants lacking the first 252 residues
      or residues 232-252 displayed compromised ATPase, protein degradation and ATP
      dependent peptide translocation abilities but retained WT-like steady-state
      peptidase activity. The binding affinities of WT and Lon mutants were evaluated
      by determining the concentration of lambda N (K(lambdaN)) needed to achieve 50%
      maximal ATPase stimulation. Comparing the K(lambdaN) values reveals that the
      region encompassing 232-252 of ELon could contribute to lambda N binding, but the
      effect is modest. Taken together, results generated from this study reveal that
      the region constituting residues 240-252 of ELon is important for ATPase
      activity, substrate translocation and protein degradation.

PMID- 22387464
TI  - Targeted transcriptional activation of silent oct4 pluripotency gene by combining
      designer TALEs and inhibition of epigenetic modifiers.
AB  - Specific control of gene activity is a valuable tool to study and engineer
      cellular functions. Recent studies uncovered the potential of transcription
      activator-like effector (TALE) proteins that can be tailored to activate user
      defined target genes. It remains however unclear whether and how epigenetic
      modifications interfere with TALE-mediated transcriptional activation. We studied
      the activity of five designer TALEs (dTALEs) targeting the oct4 pluripotency
      gene. In vitro assays showed that the five dTALEs that target distinct sites in
      the oct4 promoter had the expected DNA specificity and comparable affinities to
      their corresponding DNA targets. In contrast to their similar in vitro
      properties, transcriptional activation of oct4 by these distinct dTALEs varied up
      to 25-fold. While dTALEs efficiently upregulated transcription of the active oct4
      promoter in embryonic stem cells (ESCs) they failed to activate the silenced oct4
      promoter in ESC-derived neural stem cells (NSCs), indicating that as for
      endogenous transcription factors also dTALE activity is limited by repressive
      epigenetic mechanisms. We therefore targeted the activity of epigenetic
      modulators and found that chemical inhibition of histone deacetylases by valproic
      acid or DNA methyltransferases by 5-aza-2'-deoxycytidine facilitated dTALE
      mediated activation of the epigenetically silenced oct4 promoter in NSCs.
      Notably, demethylation of the oct4 promoter occurred only if chemical inhibitors
      and dTALEs were applied together but not upon treatment with inhibitors or dTALEs
      only. These results show that dTALEs in combination with chemical manipulation of
      epigenetic modifiers facilitate targeted transcriptional activation of
      epigenetically silenced target genes.

PMID- 22387467
TI  - Solution structure of TT30, a novel complement therapeutic agent, provides
      insight into its joint binding to complement C3b and C3d.
AB  - A novel therapeutic reagent TT30 was designed to be effective in diseases of the
      alternative pathway of complement such as paroxysmal nocturnal hemoglobinuria and
      other diseases. TT30 is constructed from the first four short complement
      regulator (SCR) domains of complement receptor type 2 (CR2) that bind to
      complement C3d, followed by the first five SCR domains of complement factor H
      that bind to complement C3b. In order to assess how TT30 binds to C3d and C3b, we
      determined the TT30 solution structure by a combination of analytical
      ultracentrifugation, X-ray scattering and constrained modeling. The sedimentation
      coefficients and radius of gyration of TT30 were unaffected by citrate or
      phosphate-buffered saline buffers and indicate an elongated monomeric structure
      with a sedimentation coefficient of 3.1 S and a radius of gyration R(G) of 6.9
      nm. Molecular modeling starting from 3000 randomized TT30 conformations showed
      that high-quality X-ray curve fits were obtained with extended SCR arrangements,
      showing that TT30 has a limited degree of inter-SCR flexibility in its solution
      structure. The best-fit TT30 structural models are readily merged with the
      crystal structure of C3b to show that the four CR2 domains extend freely into
      solution when the five complement factor H domains are bound within C3b. We
      reevaluated the solution structure of the CR2-C3d complex that confirmed its
      recent crystal structure. This recent CR2-C3d crystal structure showed that TT30
      is able to interact readily with C3d ligands in many orientations when TT30 is
      bound to C3b.

PMID- 22387466
TI  - Structure of an essential type IV pilus biogenesis protein provides insights into
      pilus and type II secretion systems.
AB  - Type IV pili (T4Ps) are long cell surface filaments, essential for microcolony
      formation, tissue adherence, motility, transformation, and virulence by human
      pathogens. The enteropathogenic Escherichia coli bundle-forming pilus is a
      prototypic T4P assembled and powered by BfpD, a conserved GspE secretion
      superfamily ATPase held by inner-membrane proteins BfpC and BfpE, a GspF-family
      membrane protein. Although the T4P assembly machinery shares similarity with type
      II secretion (T2S) systems, the structural biochemistry of the T4P machine has
      been obscure. Here, we report the crystal structure of the two-domain BfpC
      cytoplasmic region (N-BfpC), responsible for binding to ATPase BfpD and membrane
      protein BfpE. The N-BfpC structure reveals a prominent central cleft between two
      alpha/beta-domains. Despite negligible sequence similarity, N-BfpC resembles
      PilM, a cytoplasmic T4P biogenesis protein. Yet surprisingly, N-BfpC has far
      greater structural similarity to T2S component EpsL, with which it also shares
      virtually no sequence identity. The C-terminus of the cytoplasmic domain, which
      leads to the transmembrane segment not present in the crystal structure, exits N
      BfpC at a positively charged surface that most likely interacts with the inner
      membrane, positioning its central cleft for interactions with other Bfp
      components. Point mutations in surface-exposed N-BfpC residues predicted to be
      critical for interactions among BfpC, BfpE, and BfpD disrupt pilus biogenesis
      without precluding interactions with BfpE and BfpD and without affecting BfpD
      ATPase activity. These results illuminate the relationships between T4P
      biogenesis and T2S systems, imply that subtle changes in component residue
      interactions can have profound effects on function and pathogenesis, and suggest
      that T4P systems may be disrupted by inhibitors that do not preclude component
      assembly.

PMID- 22387468
TI  - N-Terminal domain of Bombyx mori fibroin mediates the assembly of silk in
      response to pH decrease.
AB  - Fibroins serve as the major building blocks of silk fiber. As the major component
      of fibroin, the fibroin heavy chain is a considerably large protein comprising N
      terminal and C-terminal hydrophilic domains and 12 highly repetitive Gly-Ala-rich
      regions flanked by internal hydrophilic blocks. Here, we show the crystal
      structure of the fibroin N-terminal domain (FibNT) at pH 4.7, revealing a
      remarkable double-layered anti-parallel beta-sheet with each layer comprising two
      FibNT molecules entangled together. We also show that FibNT undergoes a pH
      responsive conformational transition from random coil to beta-sheets at around pH
      6.0. Dynamic light scattering demonstrates that FibNT tends to oligomerize as pH
      decreases to 6.0, and electron microscopy reveals micelle-like oligomers. Our
      results are consistent with the micelle assembly model of silk fibroin and, more
      importantly, show that the N-terminal domain in itself has the capacity to form
      micelle-like structures in response to pH decrease. Structural and mutagenesis
      analyses further reveal the important role of conserved acidic residues clustered
      in FibNT, such as Glu56 and Asp100, in preventing premature beta-sheet formation
      at neutral pH. Collectively, we suggest that FibNT functions as a pH-responsive
      self-assembly module that could prevent premature beta-sheet formation at neutral
      pH yet could initiate fibroin assembly as pH decreases along the lumen of the
      posterior silk gland to the anterior silk gland.

PMID- 22387469
TI  - Catalytic versatility and backups in enzyme active sites: the case of serum
      paraoxonase 1.
AB  - The origins of enzyme specificity are well established. However, the molecular
      details underlying the ability of a single active site to promiscuously bind
      different substrates and catalyze different reactions remain largely unknown. To
      better understand the molecular basis of enzyme promiscuity, we studied the
      mammalian serum paraoxonase 1 (PON1) whose native substrates are lipophilic
      lactones. We describe the crystal structures of PON1 at a catalytically relevant
      pH and of its complex with a lactone analogue. The various PON1 structures and
      the analysis of active-site mutants guided the generation of docking models of
      the various substrates and their reaction intermediates. The models suggest that
      promiscuity is driven by coincidental overlaps between the reactive intermediate
      for the native lactonase reaction and the ground and/or intermediate states of
      the promiscuous reactions. This overlap is also enabled by different active-site
      conformations: the lactonase activity utilizes one active-site conformation
      whereas the promiscuous phosphotriesterase activity utilizes another. The
      hydrolysis of phosphotriesters, and of the aromatic lactone dihydrocoumarin, is
      also driven by an alternative catalytic mode that uses only a subset of the
      active-site residues utilized for lactone hydrolysis. Indeed, PON1's active site
      shows a remarkable level of networking and versatility whereby multiple residues
      share the same task and individual active-site residues perform multiple tasks
      (e.g., binding the catalytic calcium and activating the hydrolytic water).
      Overall, the coexistence of multiple conformations and alternative catalytic
      modes within the same active site underlines PON1's promiscuity and evolutionary
      potential.

PMID- 22387470
TI  - Identifying functionally important conformational changes in proteins: activation
      of the yeast alpha-factor receptor Ste2p.
AB  - We have developed a procedure in which disulfide cross-links are used to identify
      regions of proteins that undergo functionally important intramolecular motion.
      The approach was applied to the identification of disulfide bonds that stabilize
      the active state of the yeast alpha-mating pheromone receptor Ste2p, a member of
      the superfamily of G protein-coupled receptors. Cysteine residues were introduced
      at random positions in targeted regions of a starting allele of Ste2p that
      completely lacks cysteines. Libraries of mutated receptors were then screened for
      alleles that exhibit constitutive signaling. Two strongly activated alleles were
      recovered containing cysteine residues in transmembrane (TM) segments 5 and 6.
      Constitutive activity of these alleles was dependent on the presence of both
      introduced cysteines and was sensitive to reducing agent. Cross-linked peptides
      derived from the mutant receptors were detected by immunoblotting. Additional
      sites of cross-linking between TM segments 5 and 6 that did not lead to
      constitutive activation were also identified. These results indicate that
      relative motion of the TM segments 5 and 6 in the extracellular half of the
      membrane is sufficient to activate the receptor and that TM segment 6, but not TM
      segment 5, exhibits rotational mobility that is not associated with receptor
      activation.

PMID- 22387471
TI  - Decision-making under risk: a graph-based network analysis using functional MRI.
AB  - Adaptive behavior requires choosing effectively between options involving risks
      and potential rewards. Existing studies implicate lateral and medial prefrontal
      areas, striatum, insula, amygdala and parietal regions in specific aspects of
      decision-making. However, limited attention is given to how brain networks encode
      economic parameters in patterns of inter-regional interactions. Here, healthy
      participants underwent functional MRI while evaluating "mixed" gambles presenting
      potential gains, losses and associated outcome probabilities. Connectivity graphs
      were constructed from analyses of psychophysiological interactions across a
      comprehensive atlas of brain regions. Expected value correlated positively with
      activity within medial prefrontal and occipital cortices, and modulated effective
      connectivity across a network that extended substantially beyond these nodes.
      Value-sensitive effective connections were found to be arranged as a unitary,
      small world network in which medial and anterior-lateral prefrontal areas
      featured as hubs, characterized by dense connectivity and high shortest-path
      centrality. Further analyses revealed that the observed effective connectivity
      effects were more pertinent to dichotomous gain/loss comparisons than to
      continuous value determination. Factoring expected value into its constituent
      components, potential loss modulated connectivity across a subset of the value
      sensitive network, whereas potential gain and outcome probability were not
      significantly embodied in functional interactions. Regional response non
      linearity was excluded as an artifactual basis to the observed effects, and
      directionality inferences were confirmed by comparison of dynamic causal models.
      Our findings extend current literature demonstrating that the representation of
      value is dependent on distributed processing taking across a widespread network
      which feeds information into a limited set of integrative prefrontal nodes. This
      study also has more general paradigmatic implications for neuroeconomics,
      demonstrating the value of explicit modeling of inter-regional interactions for
      understanding the neural substrates of decisional processes.

PMID- 22387472
TI  - Spontaneous activity in developing sensory circuits: Implications for resting
      state fMRI.
AB  - The immature brain spontaneously expresses unique patterns of electrical activity
      that are believed to contribute to the development of neuronal networks. Certain
      electrographic features of this activity, particularly modulation on an infraslow
      time scale, resemble activity patterns observed in the mature brain at 'rest',
      loosely defined as the absence of an investigator imposed task. However, it is
      not clear whether the immature activity patterns observed at rest are precursors
      of the spontaneous neuronal activity that forms resting state networks in the
      adult. Here, we review recent studies that have explored the generative
      mechanisms of resting state activity during development in the primary sensory
      systems of premature human neonates and neonatal rodents. The remarkable
      hypothesis suggested by this work is that while resting state activity during the
      pre- and possibly near-term period can bear superficial resemblance to adult
      activity it is fundamentally different in terms of function and origin. During
      early development spontaneous thalamocortical activity in primary sensory regions
      is determined largely by transitory generators in the sensory periphery. This is
      in contrast to the adult, where spontaneous activity generated within
      thalamocortex, particularly by cortico-cortical connections, dominates. We
      therefore suggest a conservative interpretation of developmental mapping studies
      which are based on indirect measurement of activity (e.g. fMRI), or on the
      partitioning of EEG frequency using bands derived from adult studies. The
      generative mechanisms for brain activity at early ages are likely different from
      those of adults, and may play very different roles; for example in circuit
      formation as opposed to attention.

PMID- 22387473
TI  - Dynamic and stochastic models of neuroimaging data: a comment on Lohmann et al.
AB  - DCM is a platform for inferring the architecture of dynamical systems, combining
      a user-dependent model specification step with a Bayesian model selection scheme.
      In their critique of the model selection procedure, Lohmann et al confine
      themselves to models generated from the classic bilinear deterministic DCM.
      Although brief reference is made to recent modeling advances, such as stochastic
      DCM and nonlinear DCM, these are negatively cast as guilty of further exploding
      the combinatorial problem that is proposed to plague model selection. Yet this is
      only a problem if a naive approach is adopted towards the model generation
      process. Where the user draws on prior knowledge of the system being modeled and
      the statistical properties of the particular data set, these advances can be
      employed precisely to address the type of concerns Lohmann et al raise in their
      exemplar analysis (Fig. 6). This note provides a putative generative model for
      their data by adding stochastic effects, using independent evidence to increase
      its biological plausibility and challenging the notion that model fit should be
      assessed using simple linear correlations. Rather than encouraging reliance on
      future developments in imaging hardware and data-driven multivariate algorithms,
      informed engagement with causal models of neuronal dynamics allows imaging
      researchers develop detailed theories of brain function across a broad range of
      data sets and cognitive phenomena.

PMID- 22387476
TI  - Floating assembly of diatom Coscinodiscus sp. microshells.
AB  - Diatoms have silica frustules with transparent and delicate micro/nano scale
      structures, two dimensional pore arrays, and large surface areas. Although, the
      diatom cells of Coscinodiscus sp. live underwater, we found that their valves can
      float on water and assemble together. Experiments show that the convex shape and
      the 40 nm sieve pores of the valves allow them to float on water, and that the
      buoyancy and the micro-range attractive forces cause the valves to assemble
      together at the highest point of water. As measured by AFM calibrated glass
      needles fixed in manipulator, the buoyancy force on a single floating valve may
      reach up to 10 MUN in water. Turning the valves over, enlarging the sieve pores,
      reducing the surface tension of water, or vacuum pumping may cause the floating
      valves to sink. After the water has evaporated, the floating valves remained in
      their assembled state and formed a monolayer film. The bonded diatom monolayer
      may be valuable in studies on diatom based optical devices, biosensors, solar
      cells, and batteries, to better use the optical and adsorption properties of
      frustules. The floating assembly phenomenon can also be used as a self-assembly
      method for fabricating monolayer of circular plates.

PMID- 22387475
TI  - Inhibition of endothelial/smooth muscle cell contact loss by the investigational
      angiopoietin-2 antibody MEDI3617.
AB  - A tumor's dependence on angiogenesis for survival and growth has led to the
      advancement of a variety of blood vessel directed anticancer treatment
      strategies. Overexpression of angiopoietin-2 (Ang-2) in tumor vasculature and its
      crucial role in angiogenesis, i.e. the destabilization of endothelial/peri
      endothelial cell interactions, now raises the possibility of additional novel
      anti-angiogenic therapeutics. The present study utilized a co-culture sphere
      model to (i) demonstrate the destabilizing effect of Ang-2 on endothelial/smooth
      muscle cell contact and (ii) evaluate the impact of the investigational Ang-2
      antibody MEDI3617 on endothelial/smooth muscle cell dissociation. Real time
      imaging of spheres showed both exogenous Ang-2 and PMA induced endogenous Ang-2
      secretion resulted in sphere destabilization (loss of endothelial cells from
      smooth muscle cell core). The presence of MEDI3617 inhibited this process. To
      assess the anti-angiogenic potential of MEDI3617 in vivo, nude mice were injected
      intradermally with human renal cell carcinoma cells (Caki-1, Caki-2) and the
      number of blood vessels induced over a 3 day period was scored. MEDI3617 (2, 10,
      20 mg/kg) significantly reduced the initiation of blood vessels for both tumor
      models at all doses investigated. These data indicate that MEDI3617 treatment
      significantly impairs the initiation of angiogenesis by inhibiting the Ang-2
      mediated disruption of endothelial/muscle cell interaction associated with blood
      vessel destabilization and thereby reduces tumor cell induced angiogenesis. The
      results support the notion that targeting the angiopoietin/Tie2 axis may offer
      novel anti-angiogenic strategies for cancer treatment.

PMID- 22387477
TI  - Regulation and spatial organization of PCNA in Trypanosoma brucei.
AB  - As in most eukaryotic cells, replication is regulated by a conserved group of
      proteins in the early-diverged parasite Trypanosoma brucei. Only a few components
      of the replication machinery have been described in this parasite and regulation,
      sub-nuclear localization and timing of replication are not well understood. We
      characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to
      establish a spatial and temporal marker for replication. Interestingly, PCNA
      distribution and regulation is different compared to the closely related
      parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly
      detectable during S phase of the cell cycle but in contrast to T. cruzi they are
      not preferentially located at the nuclear periphery. Furthermore, PCNA seems to
      be degraded when cells enter G2 phase in T. brucei suggesting different modes of
      replication regulation or functions of PCNA in these closely related eukaryotes.

PMID- 22387474
TI  - Neuroimaging in aphasia treatment research: consensus and practical guidelines
      for data analysis.
AB  - Functional magnetic resonance imaging is the most widely used imaging technique
      to study treatment-induced recovery in post-stroke aphasia. The longitudinal
      design of such studies adds to the challenges researchers face when studying
      patient populations with brain damage in cross-sectional settings. The present
      review focuses on issues specifically relevant to neuroimaging data analysis in
      aphasia treatment research identified in discussions among international
      researchers at the Neuroimaging in Aphasia Treatment Research Workshop held at
      Northwestern University (Evanston, Illinois, USA). In particular, we aim to
      provide the reader with a critical review of unique problems related to the pre
      processing, statistical modeling and interpretation of such data sets. Despite
      the fact that data analysis procedures critically depend on specific design
      features of a given study, we aim to discuss and communicate a basic set of
      practical guidelines that should be applicable to a wide range of studies and
      useful as a reference for researchers pursuing this line of research.

PMID- 22387478
TI  - Trehalose as an indicator of desiccation stress in Drosophila melanogaster
      larvae: a potential marker of anhydrobiosis.
AB  - In the current scenario of global climate change, desiccation is considered as
      one of the major environmental stressors for the biota exposed to altered levels
      of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan
      terrestrial insect has been chosen as a humidity-sensitive bioindicator model for
      the present study since its habitat undergoes frequent stochastic and/or
      seasonally aggravated dehydration regimes. We report here for the first time the
      occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to
      desiccation stress under laboratory conditions. Larvae desiccated for ten hours
      at <5% relative humidity could enter anhydrobiosis and could revive upon
      rehydration followed by resumption of active metabolism. As revealed by FTIR and
      HPLC analyzes, our findings strongly indicated the synthesis and accumulation of
      trehalose in the desiccating larvae. Biochemical measurements pointed out the
      desiccation-responsive trehalose metabolic pathway that was found to be
      coordinated in concert with the enzymes trehalose 6-phosphate synthase and
      trehalase. Further, an inhibitor-based experimental approach using
      deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role
      of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose
      trehalose as a potential marker for the assessment of anhydrobiosis in
      Drosophila. The present findings thus add to the growing list of novel
      biochemical markers in specific bioindicator organisms for fulfilling the urgent
      need of environmental biomonitoring of climate change.

PMID- 22387479
TI  - Robust stability analysis of a class of neural networks with discrete time
      delays.
AB  - This paper studies the existence, uniqueness and global asymptotic stability of
      the equilibrium point for the class of neural networks with discrete constant
      time delays under parameter uncertainties. The class of the neural network
      considered in this paper employs the activation functions which are assumed to be
      continuous and slope-bounded but not required to be bounded or differentiable. We
      conduct a stability analysis by exploiting the stability theory of Lyapunov
      functionals and the theory of Homomorphic mapping to derive some easily
      verifiable sufficient conditions for existence, uniqueness and global asymptotic
      stability of the equilibrium point. The conditions obtained mainly establish some
      time-independent relationships between the network parameters of the neural
      network. We make a detailed comparison between our results and the previously
      published corresponding results. This comparison proves that our results are new
      and improve and generalize the results derived in the past literature. We also
      give some illustrative numerical examples to show the effectiveness and
      applicability of our proposed stability results.

PMID- 22387480
TI  - Effect of second language exposure on brain activity for language processing
      among preschoolers.
AB  - We investigated brain activity in 3-5-year-old preschoolers as they listened to
      connected speech stimuli in Japanese (first language), English (second language),
      and Chinese (a rarely exposed, foreign language) using near-infrared
      spectroscopy. Unlike the younger preschoolers who had been exposed to English for
      almost 1 year, brain activity in the bilateral frontal regions of the older
      preschoolers who had been exposed to English for almost 2 years was higher for
      Japanese and English speech stimuli than for Chinese. This tendency seemed to be
      similar to that observed in adults who had learned English for some years. These
      results indicate that exposure to a second language affects brain activity to
      language stimuli among preschoolers.

PMID- 22387482
TI  - In vitro effect of clinical propofol concentrations on red blood cell aggregation
      and deformability.
AB  - This in vitro study investigated time-related effects of propofol at the plasma
      concentrations required for sedation and general anaesthesia, on RBC aggregation,
      deformability, and morphology. Blood containing propofol at plasma concentrations
      of 0, 2 and 4 MUg ml-1 was incubated in a water bath at 37 degrees C for 1, 2, or
      4 hours. RBC elongation indices (EIs) and aggregation indices (AIs), which
      represent RBC deformability and aggregation, respectively, were measured. Also,
      RBC morphological indices (MIs), which represent RBC morphology, were calculated.
      EIs and AIs were similar at propofol concentrations of 0, 2, or 4 MUg ml-1 after
      1, 2, or 4 hours of incubation. MIs at propofol plasma concentrations 0 or 2 MUg
      ml-1 were similar after 1, 2, and 4 hours of incubation, however, MI at a
      propofol concentration of 4 MUg ml-1 after 4 hours of incubation was higher than
      its value after 1 or 2 hours of incubation. No significant difference was
      observed between MIs at propofol plasma concentrations 0, 2, or 4 MUg ml-1 after
      1, 2, and 4 hours of incubation. At clinical doses, propofol has no direct
      effects on RBC deformability, aggregation, or morphology over a 4 hours
      incubation period.

PMID- 22387483
TI  - Prevalence and predictors of slow flow in angiographically normal coronary
      arteries.
AB  - BACKGROUND: One out of 5 patients undergoing coronary angiography has
      angiographically normal coronary arteries (ANCA). Some of them have abnormally
      slow coronary flow (SCF). The prevalence and causes of SCF in these patients are
      not clear. METHODS: We studied 114 consecutive patients with ANCA. Each angiogram
      was independently evaluated by 2 physicians unaware of all other clinical
      features of the case. Coronary flow (CF) was graded using the corrected TIMI
      Frame Count (cTFC) and Coronary Clearance Frame Count (CCFC) methodologies. SCF
      was defined as a cTFC exceeding the reported normal (mean cTFC + 2 SD) in each of
      the three major coronary arteries. The association between SCF and various
      clinical, inflammatory, and metabolic variables was tested using a multivariable
      analysis model. RESULTS: Thirty-nine (34%) patients had SCF. Inter-individual CF
      varied substantially among them (range 10-143 frames/sec, mean: 37 +/- 22
      frames/sec). The intra-individual CF did not vary: CF correlated well in the
      three major epicardial coronary arteries of a given individual (r = 0.7, p =
      0.0001). Multivariable analysis revealed that current smoking was the most
      significant variable related to SCF (odds ratio = 4.7, p = 0.006, CI 95% 1.6
      13.3). The SCF group included significantly more smokers (41% versus 15%, p =
      0.002). CONCLUSIONS: SCF is a common finding (34%) among patients with
      angiographically normal coronary arteries. In these patients, slow flow is a
      systemic phenomenon that involves all three coronary arteries rather than a local
      event and is associated with current smoking.

PMID- 22387484
TI  - The NO-donor FK409 improves mechanical properties of activated neonatal PMN.
AB  - BACKGROUND: Activated polymorphonuclear neutrophils (PMN) play an important role
      in the microcirculation. Nitric oxide (NO) reduces the sequestration of PMN in
      the narrow vessels of various organs and, therefore, may reduce organ injury
      during inflammation. OBJECTIVES: Since PMN of term neonates show various
      functional differences compared to PMN in adults (decreased chemotaxis, decreased
      intracellular killing, decreased adhesion), we studied the influence of the semi
      synthetical NO-donor FK-409 (4-Ethyl-2-hydroxyimino-5-nitro-3-hexenamide) on the
      deformability of IL-8 activated PMN in term neonates and adults. METHODS: A cell
      transit analyzer (CTA) was used to study transit times of individual PMN through
      8 MUm filter pores, neutrophil elastase concentrations were determined by enzyme
      immunoessay and activation of PMN was classified by mircroscopic evaluation.
      RESULTS: The transit times of PMN activated by IL-8 in adults were 9.3 +/- 2.9 s,
      in term neonates 10.7 +/- 3.3 s. FK-409 improved the transit time of activated
      PMN in adults (5.4 +/- 1.6 s) and in term neonates (5.6 +/- 1.1 s). Despite of
      the functional differences of PMN in term neonates and adults, the improvement of
      the transit times by FK-409 was not different between the two groups. The NO
      donor decreased the neutrophil elastase concentrations and the morphological
      signs of activation in neonates and adults. CONCLUSIONS: We conclude that the NO
      donor FK-409 improves the microcirculation by increasing the deformability of IL
      8 activated PMN. NO may reduce in neonates tissue damage by reduced PMN
      sequestration due to decreased PMN rigidity.

PMID- 22387485
TI  - D-A-pi-A featured sensitizers bearing phthalimide and benzotriazole as auxiliary
      acceptor: effect on absorption and charge recombination dynamics in dye
      sensitized solar cells.
AB  - Two organic D-A-pi-A sensitizers LS-2 and WS-5 containing N-octyl substituted
      phthalimide and benzotriazole as auxiliary electron withdrawing units with
      similar dimension and structure architecture were systematically studied,
      focusing on photophysical and electrochemical as well as photovoltaic properties
      in nanocrystalline TiO(2)-based dye-sensitized solar cells (DSSCs).
      Interestingly, with similar five-member benzo-heterocycles, the two auxiliary
      acceptors of phthalimide and benzotriazole play exactly different roles in
      absorption and intramolecular charge transfer: (i) in contrast with WS-5
      delocalized throughout the entire chromophore, the HOMO orbital of LS-2 is mainly
      located at the donor part due to the twist conformation with the existence of two
      carbonyl groups in phthalimide; (ii) the dihedral angles of "D-A" plane and "A
      pi" plane in LS-2 further suggest that the incorporation of phthalimide moiety
      results in curvature of electron delocalization over the whole molecule, in
      agreement with its blue-shifted, relatively narrow absorption spectra and low
      photocurrent density; (iii) in contrast with the beneficial charge transfer of
      benzotriazole in WS-5, the phthalimide unit in LS-2 plays an oppositely negative
      contribution to the charge transfer, that is, blocking intramolecular electron
      transfer (ICT) from donor to acceptor to some extent; and (iv) in electrochemical
      impedance spectroscopy, the incorporated benzotriazole unit enhances electron
      lifetime by 18.6-fold, the phthalimide only increases electron lifetime by 5.0
      fold. Without coadsorption of chenodeoxylic acid (CDCA), the DSSCs based on WS-5
      exhibited a promising maximum conversion efficiency (eta) of 8.38% with
      significant enhancement in all photovoltaic parameters (J(SC) = 15.79 mA cm(-2),
      V(OC) = 791 mV, ff = 0.67). In contrast, with the very similar D-A-pi-A feature
      changing the additional acceptor from benzotriazole to phthalimide unit, the
      photovoltaic efficiency based on LS-2 was only 5.11%, decreased by 39%, with less
      efficient photovoltaic parameters (J(SC) = 10.06 mA cm(-2), V(OC) = 748 mV, ff =
      0.68). Therefore, our results demonstrate that it is essential to choose proper
      subsidiary withdrawing unit in D-A-pi-A sensitizer configuration for DSSCs.

PMID- 22387497
TI  - Identification of a diacylglycerol acyltransferase 2 gene involved in pheromone
      biosynthesis activating neuropeptide stimulated pheromone production in Bombyx
      mori.
AB  - Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triacylglycerol
      biosynthesis. In the present study, a DGAT2 gene from Bombyx mori was
      characterized. Temporal expression profiles indicated that BmDGAT2 steadily
      increased from 96 h before eclosion (-96 h) to an expression peak in the
      pheromone glands (PGs) of new-emerged female (0 h), a key stage for sex pheromone
      production. Spatial expression analysis revealed that the BmDGAT2 transcript was
      most richly expressed in PGs. Decapitation and subsequent methoprene, a juvenile
      hormone (JH) analog, treatment experiments revealed that JH had no influence on
      the expression of BmDGAT2 transcript before emergence, but inhibited the
      expression of BmDGAT2 transcript when administered to newly emerged adults.
      Further RNAi analysis confirmed that the decrease in BmDGAT2 mRNA level caused a
      significant reduction in sex pheromone production. Thus, DGAT2 is a key enzyme
      regulating B. mori sex pheromone synthesis and release.

PMID- 22387498
TI  - Effects of decreased O2 and elevated CO2 on survival, development, and gene
      expression in cowpea bruchids.
AB  - Use of modified atmospheres with depleted O(2) and/or elevated CO(2) is an
      environmentally friendly alternative to currently used fumigants for control of
      stored grain insect pests. In the present study, we examined the impact of
      hypoxia and hypercapnia on cowpea bruchids (Callosobruchus maculatus), a storage
      pest of cowpea and other legumes. Two O(2)/CO(2) combinations were used; (i) 10%
      O(2)+10% CO(2), (ii) 2% O(2)+18% CO(2). In both cases, N(2) was maintained at
      80%, equivalent to normal atmospheric concentration. In ambient atmosphere, the
      rate of O(2) consumption and CO(2) output at different stages (from low to high)
      was: eggs~1st instar<2nd instar~pupae~adults<3rd instar<4th instar. When exposed
      to 10% O(2)+10% CO(2), eggs, larvae and pupae were able to complete development
      and successfully enter the next developmental stage, although developmental time
      and mortality varied at different stages. In contrast, more severe
      hypoxic/hypercapnic treatment, i.e. 2% O(2)+18% CO(2), led to cessation of
      development of all stages. Effects on eggs and adults were most dramatic as they
      could only withstand 2-3 days exposure. Further, eggs at early (4-6h old) and
      later stages (102-104 h old, black-headed) were more susceptible compared to
      those at intermediate stage (52-54 h old). The 3rd and 4th instar larvae were
      least sensitive and could survive up to 20 days treatment. To gain some insight
      into molecular mechanisms underpinning the hypoxic/hypercarpnic response, we
      performed qPCR reactions on selected metabolic genes involved in TCA cycle and in
      protein digestion, as well as genes encoding stress-responsive heat shock
      proteins. Patterns of gene expression and proteolysis suggest that cowpea
      bruchids suppress their metabolic activity and increase stress tolerance when
      challenged by O(2) deprivation. Transcript abundance as well as proteolytic
      activity recovered once normoxic conditions resumed. Taken together, cowpea
      bruchids were found able to cope with hypoxic and hypercapnic stress. This
      ability was particularly strong in the late larval stage.

PMID- 22387499
TI  - Genetic characterization of Trypanosoma brucei circulating in domestic animals of
      the Fontem sleeping sickness of Cameroon.
AB  - To improve our knowledge on the transmission dynamics of trypanosomes,
      Trypanosoma brucei was identified in domestic animals of the Fontem sleeping
      sickness focus of Cameroon and their genetic characterizations were performed
      using seven polymorphic microsatellite markers. About 397 domestic animals
      including 225 pigs, 87 goats, 65 sheep and 20 dogs were sampled. The card
      agglutination test for trypanosomiasis was positive for 254 (63.98%) animals
      while the parasitological examinations (thin blood film and capillary tube
      centrifugation) revealed 86 (21.66%) trypanosome infections. The PCR based method
      revealed 140 (35.26%) infections of trypanosomes of the subgenus Trypanozoon. The
      genetic characterization of these 140 positive samples revealed 89 different
      alleles: 82 in pigs, 72 in goat, 60 in sheep and 48 in dog. Whatever the
      microsatellite marker used, most of positive samples were amplified. However, the
      sensitivity (percentage of samples amplified for each marker) of these markers
      varies significantly between them (chi(2) = 120.32; P < 0.0001). This study
      showed a high level (80.00%) of mixed genotypes as well as a wide range of T.
      brucei genotypes circulating in domestic animals of the Fontem sleeping sickness
      focus of Cameroon. This indicates that several T. brucei genotypes can naturally
      be transmitted simultaneously to tsetse flies during a single blood meal.

PMID- 22387502
TI  - New perspectives in neurotrauma research.

PMID- 22387500
TI  - TF--a novel cell-permeable and selective inhibitor of human protein kinase CK2
      induces apoptosis in the prostate cancer cell line LNCaP.
AB  - BACKGROUND: Abnormally high activity of protein kinase CK2 is linked to various
      diseases including cancer. Therefore, the inhibition of CK2 is a promising
      therapeutic strategy to fight this disease. METHODS: We screened a library of
      synthetic molecules concerning their capacity to inhibit CK2. The activity of CK2
      and their IC50 and Ki values were determined by a capillary electrophoresis
      assay. The effects of the inhibitor in a cell culture model were analyzed by cell
      counting, a viability assay, cytofluorimetry and Western blot. RESULTS: The best
      CK2 inhibitor found in this screen was 6,7-dichloro-1,4-dihydro-8-hydroxy-4-[(4
      methylphenylamino)methylen]dibenzo [b,d]furan-3(2H)-one, which we refer to as
      "TF". TF showed tight binding to CK2 with low IC50 (29 nM) and Ki (15 nM) values.
      TF inhibited only seven out of 61 human kinases tested (>70% inhibition).
      Incubation of LNCaP cells with 50 MUM TF for 48 h decreased the intracellular CK2
      activity by 50%, confirming that the inhibitor is membrane permeable. The
      decrease in activity was correlated with a severe reduction in cell viability.
      The reduction in cell viability is at least partly due to the induction of
      apoptosis. GENERAL SIGNIFICANCE: In many cancers the protein kinase CK2 is
      significantly up-regulated and supports the neoplastic phenotype. New therapeutic
      strategies should be based on diverse reliable inhibitors to reverse the abnormal
      high levels to normal settings.

PMID- 22387503
TI  - The incidence and outcome of severe brain trauma - Design and first results of an
      epidemiological study in an urban area.
AB  - Epidemiological data on the incidence, the prehospital and hospital care and the
      outcome of traumatic brain injury in Germany are scarce. It is therefore
      difficult to estimate the importance of this injury with respect to magnitude as
      well as effectiveness and efficiency of therapeutic concepts. We therefore
      planned a study that was supposed to provide population based epidemiological
      data in the field of severe brain trauma from the site of the accident until
      discharge from hospital.All 90.000 prehospital emergencies that were cared for by
      emergency physicians in Cologne from January 1990 until December 1996 were
      screened for identification of severe brain trauma. Their clinical course was
      reviewed using standard records and patients were included if they had their
      accident within the city of Cologne and fullfilled the final inclusion criteria
      of GCS <= 8 or AISHead >= 3. 650 eligible patients were identified of whom 530
      had complete datasets (follow-up 80 %). Univariate statistical analysis was
      performed for all relevant variables. The main study endpoints were incidence and
      outcome of severe brain trauma.The annual incidence of severe brain trauma in
      Cologne (1 mio. inhabitants) was 93. The average age was 39 years and 71 % of the
      patients were male. The average prehospital GCS was 6.8, the average prehospital
      Trauma Score was 8.3 points. 49 % of the study population suffered from multiple
      injuries. The overall mortality rate was 46,6 %. 60 % of deaths occurred within
      the prehospital setting.The incidence of severe brain trauma in Cologne in this
      study was significantly lower compared to what could be expected from the
      literature. The overall mortality was high, especially the high prehospital death
      rate is striking.

PMID- 22387504
TI  - Quality of Life after traumatic brain injury: A systematic review of the
      literature.
AB  - In modern industrial countries traumatic brain injury (TBI) is a common sequel
      after different kinds of accidents especially amongst young male adults. Apart
      from medical and economic consequences Quality of Life (QoL) after TBI becomes
      increasingly important in outcome assessment. Besides the classical domains of
      QoL (physical, psychological, social) cognitive impairments are playing an
      important role especially for TBI patients. In 1991 the Meran conference set
      important standards and formulated basic guidelines for defining and measuring
      QoL in surgery, but a special index for TBI patients has not yet been developed.
      Instead, QoL research concentrates on physical, medical, psychological and social
      problems only. Based on the existing QoL concept extended by the cognitive aspect
      it was the aim of this review to give an overview about the recent QoL research
      in TBI patients since 1991. Sixteen studies in TBI patients mentioning at least 2
      domains of QoL (physical, psychological, social, cognitive) were published since
      1991. Five of them considered all 4 domains of QoL. All studies except of one
      dealt with psychological and social problems. Only half of the studies considered
      cognitive impairments. Four studies tried to define QoL, but none of them
      included the cognitive component. There was no consensus regarding the definition
      and the choice of measurement instrument for QoL after TBI. This review of 16
      studies considering outcome and QoL after TBI confirms that a homogenous and
      clinically relevant QoL concept for this group of patients is still missing.
      Further research in TBI patients should include all 4 domains of QoL.

PMID- 22387505
TI  - Biochemical changes and gene expression following traumatic brain injury: Role of
      spreading depression.
AB  - The effects of spreading depression-like DC depolarizations on biochemical
      changes and gene expression were examined following trau-matic neocortical
      lesions, as induced by transcranial cold injury. The surrounding of traumatic
      cold lesions was characterized by increased glu-cose and lactate contents,
      without major disturbances of protein synthesis or energy state. A transient pH
      decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline
      values by 3 h. These changes were similar in animals with spontaneous spreading
      depression-like DC shifts (n = 14) and those without spreading depressions (n =
      7), but there was a marked difference in the gene response. In injured animals
      without SD, only a short-lasting response of c-fos, junB, c-jun and MKP-1 mRNAs
      as well as c-Fos protein was bilaterally found in the piri-form cortex, and -
      with ipsilateral dominance - the dentate gyrus and hippocampal CA3/4 fields at 1
      h after lesioning. In injure d animals with spreading depressions, on the
      contrary, a strong elevation was seen in layers II-IV and VI of the injury-remote
      ipsilateral cerebral cortex, which persisted over as long as 6 h. The expression
      of c-fos, junB and MKP-1 mRNAs was closely related to the time interval between
      the last spreading depression and the end of the experiments. Levels were highest
      shortly after transient DC shifts, and decreased thereafter mono-exponentially
      with half-lives of 48, 75 and 58 min for c-fos, junB and MKP-1 mRNAs,
      respectively. Thus, spreading depression is a prominent factor influencing the
      trauma-related gene response, but - in contrast to focal ischemia - it does not
      aggravate the metabolic dysfunction.

PMID- 22387506
TI  - Protein S-100B and neuron specific enolase as early neurobiochemical markers of
      the severity of traumatic brain injury.
AB  - The present study aimed at the predictive value of early release patterns of
      protein S-100B and neuron specific enolase (NSE) in patients with traumatic brain
      injury. We investigated 69 patients who were admitted to the Department of
      Neurosurgery following traumatic brain injury. Both NSE and S-100B serum
      concentrations during the first three days after admission were highly and
      significantly correlated with Glasgow Coma and Coma Remission Scale scores at the
      respective blood sampling times as well as 2 weeks later. Signs of intracranial
      pathology as evaluated by CCT or MRI scans showed no association with NSE or S
      100B release patterns. Our data support the hypothesis that NSE and protein S
      100B are useful and sensitive neurobiochemical markers for the early clinical
      outcome of traumatic brain injury.

PMID- 22387507
TI  - Mechanisms underlying the pathogenesis of urinary bladder instability - new
      perspectives for the treatment of reflex incontinence.
AB  - The urine storage ability of the urinary bladder is markedly impaired following
      inflammation of the urinary bladder and spinal cord injury because of a
      hyperexcitability of micturition reflexes. Using two rat models of inflammation
      induced bladder overactivity and detrusor hyper-reflexia following spinal cord
      injury we investigated changes in the neuronal pathways to the urinary bladder
      which may underlie the development of this instability. Our results suggest that
      among the factors involved in inflammation-induced bladder instability are
      significant changes in the expression of the neuropeptides substance P,
      calcitonin gene-related peptide and galanin at the primary afferent level, as
      well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and
      postganglionic efferent level. In the lumbar and sacral spinal cord nNOS
      immunoreactivity was depleted from dorsal horn neurones in both cystitis and
      spinal cord injured rats and from preganglionic parasympathetic neurones after
      spinal cord injury. Distension of the bladder in chronically spinalized rats
      elicited c-Fos expression in a significantly greater number of neurones
      throughout the lumbar and sacral segments than in rats with an intact neuraxis.
      Thus, under pathological conditions rather complicated changes in the synthesis
      of neuropeptides and nNOS occur at the primary afferent, spinal cord and
      postganglionic efferent level that together control the activity of the urinary
      bladder. Further mechanisms like unmasking of silent synapses and axonal
      sprouting in the spinal cord might further contribute to an increase in activity
      in micturition reflex pathways. Local cooling of the dorsal spinal cord at the
      level L6/S1 with temperatures between 14 and 20  degrees C proved a simple
      technique to control the unstable bladder and restore continence in both
      inflammation-induced detrusor overactivity and detrusor hyperreflexia following
      spinal cord injury. The effects of cooling are probably the result of a blockade
      of synaptic transmission within the dorsal cord which eliminates neuronal
      overactivity. Thus, local spinal cord cooling could offer a new method to treat
      bladder instability and reflex incontinence.

PMID- 22387508
TI  - Molecular plasticity of retinal ganglion cells after partial optic nerve injury.
AB  - In the past few years we established the partial crush of the optic nerve as an
      in vivo model system for the study of signaling pathways involved in molecular
      plasticity after axonal injury. The simplicity of this model at the cellular
      level allows decisive questions to be anwsered whilst functional aspects of
      visual information processing can be studied in parallel. A major advantage of a
      partial optic nerve crush model is the opportunity to directly compare different
      cell populations: (i) the rapidly degenerating retinal ganglion cells (RGC), (ii)
      the axotomized RGC population that eventually dies over the period of the next
      few weeks, (iii) the axotomized RGC population surviving for a long time in the
      retina without an axon and (iv) the surviving RGC population that maintains
      axonal connections to their brain targets. Thus, differential aspects of post
      lesion plasticity can be analyzed. Using this axonal injury model we investigated
      the expression of immediate early genes, glutamate receptors, and other
      differentially expressed genes that we identified with a combined subtractive
      hybridization and suppression polymerase chain reaction (PCR) screen. Moreover,
      we characterized time course of cell death, the astroglia response of the retina
      and optic nerve as well as the topography of anterograde and retrograde axonal
      transport.

PMID- 22387509
TI  - Influence of age-related factors on long-term outcome after traumatic brain
      injury (TBI) in children: A review of recent literature and some preliminary
      findings.
AB  - Cerebral plasticity of the immature brain is often inferred to lead to less
      serious consequences of early traumatic brain injury (TBI) in the pediatric age
      group. This notion is seriously challenged by recent research findings. Data from
      prospective studies point to some children's dif-ficulties in ongoing skill
      acquisition and the possibility of late-emerging deficits. Accordingly,
      preliminary group data of an own ongoing study support the notion of an increased
      risk for pervasive neuropsychological impairment in subjects with severe TBI and
      early age at trauma. The pattern of neuropsychological deficits may depend on the
      developmental level at the time of injury, although effects of hemispheric site
      of lesion were also found to persist in individual cases. Theoretical
      considerations and empirical findings stress the importance of a longitudinal
      developmental perspective for the evaluation of long-term outcome after pediatric
      TBI. ("Verbund Neurotrauma Kiel / Project 4: Evaluation of neurological
      rehabilitation and course of cognitive development in children and adoles-cents
      with secondarily acquired brain damage", funded through the Research Program
      "Gesundheit 2000" of the German government, FKZ 01 KO 9512.).

PMID- 22387510
TI  - Assessment of sensorimotor functions after traumatic brain injury (TBI) in
      childhood - Methodological aspects.
AB  - Various basic qualitative and quantitative methods for the evaluation of
      sensorimotor functions after Traumatic Brain Injury (TBI) are introduced and
      discussed. Methodological aspects are illustrated by a single case follow-up
      study of a child after severe TBI (age 11; 7?12;1 yrs; 6, 8 and 12 month post
      TBI) in comparison to an age-matched healthy control group (N=16). The evaluation
      consisted of neurological investigation, Barthel-Index, Terver Numeric Score for
      Functional Assessment, Rappaport Disability Rating Scale (modified version), a
      coordination-test for children (KTK), a pilot-tested Motor Function Score,
      quantitative evaluation of spatiotemporal gait parameters on a walkway and on a
      treadmill, and the kinematic assessment of hand motor functions. Quantitative
      movement analyses revealed two general types of motor disorder: Slowing of
      movements and compensatory motor strategies. Averaged z-scores showed deficits,
      which were pronounced in fine motor skills (hand movements: 1.86, gait: 1.3).
      During follow-up, a strong improvement rate during the first (-0.48 z-scores) and
      nearly no improvement rate (-0.03 z-scores) during the second time interval was
      seen. Clinical scores and developmental tests were not able to document the whole
      restitutional course, whereas motor tests with special emphasis on functional
      aspects and the quantitative movement assessment seemed to be suitable methods.
      We conclude that a sufficient evaluation of sensorimotor functions after TBI in
      childhood needs an increase in procedural uniformity on onehand and the
      combination of various qualitative and quantitative methods on the other hand. To
      connect both claims, further research is necessary.

PMID- 22387511
TI  - An early onset rehabilitation program for children and adolescents after
      traumatic brain injury (TBI): Methods and first results.
AB  - Survived traumatic brain injuries (TBI) are one of the most serious challenges to
      the patient's future life. Recent literature increasingly questions the long
      believed protective effects of functional cerebral plasticity in children.
      Although TBI in children and adolescents is frequent, they are less frequently
      admitted to rehabilitation centers as in-patients than adults. This emphasizes
      the role of out-patient treatment. The progressing study described here aims to
      achieve a contribution to a comprehensive approach in TBI-rehabilitation for
      youngsters. A two-stage multimethodal program, starting with stimulation in coma
      while the patient is on the intensive care unit, and neuropsychological therapy
      after regaining consciousness is to be evaluated in a controlled, prospective and
      randomized study. After including nearly 50 % of the planned sample (100
      persons), some preliminary results can be mentioned with all applicable caution.
      The effectiveness of the applied therapy can be stated here with respect to the
      posttraumatic development of intellectual abilities in the 6- and 12 months
      follow ups. Moreover, in the control group development of psychopathological
      alterations was found to a considerable degree and also lower ratings in a
      quality of life questionnaire, compared to the experimental group. It is expected
      to prove these differences statistically, after the total sample has been
      included, and thus equal distributions have been achieved in all predictive
      variables.

PMID- 22387512
TI  - Motor rehabilitation after traumatic brain injury and stroke - Advances in
      assessment and therapy.
AB  - A long-term goal in motor rehabilitation is that treatment is not selected on the
      basis of 'schools of thought', but rather, based on knowledge about efficacy and
      effectiveness of specific interventions for specific situations (e.g. functional
      syndromes). Motor dysfunction after stroke or TBI can be caused by many different
      functional syndromes such as paresis, ataxia, deafferentaion, visuo-perceptual
      deficits, or apraxia. Examples are provided showing that theory-based analysis of
      motor behavior makes it possible to describe 'syndrome-specific motor deficits'.
      Its potential implications for motor rehabilitation are that our understanding of
      altered motor behavior as well as specific therapeutic approaches might be
      promoted. A methodological prerequisite for clinical trials in rehabilitation is
      knowledge about test properties of assessment tools in follow-up situations such
      as test-retest reliability and responsiveness to change. Test-retest reliability
      assesses whether a test can produce stable measures with test repetition, while
      sensitivity to change reflects whether a test detects changes that occur over
      time. Exemplifying these considerations, a reliability and validity study of a
      kinematic arm movement analysis is summarized. In terms of new therapeutic
      developments, two examples of clinical therapeutic studies are provided assessing
      the efficacy of specific inter-ventions for specific situations in arm and gait
      rehabilitation: the Arm Ability Training for high functioning hemiparetic stroke
      and TBI patients, and the treadmill training for non-ambulatory hemiparetic
      patients. In addition, a new technical development, a machine-controlled gait
      trainer ist introduced.

PMID- 22387513
TI  - Temporal constraints of perceiving, generating, and integrating information:
      Clinical indications.
AB  - Neuropsychological research on temporal constraints of perception and motor
      performance can add important information to research on human behavior. Without
      considering temporal mechanisms of perceiving, generating, and updating
      information, brain mechanisms can never be fully understood. In this study
      temporal aspects of performance in psychophysical experiments on three different
      temporal levels (around 30 ms, 300 ms, and 3000 ms) were investigated in patients
      with acquired brain lesions and a control group without neurological deficits.
      The patients had acquired focal brain lesions in: anterior (pre-central) regions
      of the left hemisphere (with non-fluent aphasia), posterior (post-central)
      regions of the left hemisphere (with fluent aphasia), the left hemipshere in
      predominantly subcortical regions (without aphasia), or anterior (pre-central) or
      posterior (post-central) regions of the right hemipshere. Perception of temporal
      order (20 to 60 ms) was impaired in patients with left-hemispheric post-central
      lesions; repetitive voluntary action (300 to 500 ms) was affected mostly in
      patients with left hemi-spheric lesions, both pre-central and post-central; and a
      deficit in integrating (2000 ms to 3000 ms) information was most pronounced in
      patients with left and right pre-central lesions. These findings provide insight
      into the associations between different levels of temporal organisation and
      circumscribed regions of the neocortex.

PMID- 22387514
TI  - Reorganization in the primary motor cortex after spinal cord injury - A
      functional Magnetic Resonance (fMRI) study.
AB  - Activation maps in the primary motor cortex (M1) were investigated in three
      patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in
      one patient with an incomplete spinal cord injury at level L1 during right elbow
      (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot
      (3 patients during imagined, 1 patient during executed) movements using
      functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI
      activation maps of patients with complete paraplegia showed a cranial
      displacement of the activation maxima in the contralateral primary motor cortex
      during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements
      were not altered. The patient with an incomplete spinal cord injury revealed no
      displacement of elbow activation maxima. The reorganization is likely to occur on
      the cortical and not on the spinal level.

PMID- 22387515
TI  - Sacral electrical neuromodulation as an alternative treatment option for lower
      urinary tract dysfunction.
AB  - Temporary electrical stimulation using anal or vaginal electrodes and an external
      pulse generator has been a treatment modality for urinary urge incontinence for
      nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical
      stimulation of the sacral spinal nerves using a permanently implanted sacral
      foramen electrode and a battery powered pulse generator for treatment of
      different kinds of lower urinary tract dysfunction, refractory to conservative
      treatment. At our department chronic unilateral electrical stimulation of the S3
      sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in
      43 patients with a mean postoperative follow up of 43,6 months. Lasting
      symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients
      with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary
      retention (85,7 %). Implants offer a sustained therapeutic effect to treatment
      responders, which is not achieved by temporary neuromodulation. Chronic
      neuromodulation should be predominantly considered in patients with urinary
      retention. Furthermore in patients with motor urge incontinence, refusing
      temporary techniques or in those requiring too much effort to achieve a sustained
      clinical effect. Despite high initial costs chronic sacral neuromodulation is an
      economically reasonable treatment option in the long run, when comparing it to
      the more invasive remaining therapeutic alternatives.

PMID- 22387516
TI  - Sacral anterior root stimulation and posterior rhizotomy in spastic neuropathic
      bladder.
AB  - The combination of sacral anterior root stimulation (SARS) and posterior
      rhizotomy is a successful procedure for the restoration of bladder function after
      supraconal spinal cord injury. Today, complete posterior rhizotomy has become
      part of the standard therapy. Conventional SARS leads to simultaneous activation
      of both the detrusor muscle and the external urethral sphincter. We evaluated the
      possibilities of different neurostimulation techniques to overcome stimulation
      induced detrusor-sphincter-dyssynergia and to achieve physiological voiding.
      Selective detrusor activation improves current sacral neurostimulation of the
      bladder, including the ?poststimulus voiding? principle. Selec-tive
      neurostimulation is possible in the following techniques: anodal block, high
      frequency block, depolarizing prepulses, sinusoidal pulses and cryoblock. The
      anodal block technique and cryotechnique are excellent methods for selective
      bladder activation to avoid detrusor-sphinc-ter-dyssynergia and thus improve
      stimulation-induced voiding. Our experience has shown that future modern
      selective bladder neurostimulation systems will be based on either the anodal
      block technique or the cryotechnique.

PMID- 22387517
TI  - Neuronal and behavioral discrimination between upward and downward pulse interval
      modulation in cochlea implanted gerbils.
AB  - Speech coding strategies for cochlear implants commonly use amplitude modulations
      of constant high rate pulses to differentially stimulate separate frequency
      channels in the cochlea. Thereby, time domain information in the fine structure
      of speech sounds, especially on transients, is largely lost. In gerbils with a
      single electrode cochlear implant was explored, whether upward and downward
      interval modulation of pulse trains can carry discriminable information. This
      question was pursued with unit recordings in primary auditory cortex (AI) and
      with behavioral discrimination training in a shuttle box. Units in AI showed
      multiple differences in the dynamic responses to the two directions of interval
      modulation and notably ON-response dominated patterns with increasing intervals
      and OFF-response dominated patterns with decreasing intervals of stimulation. In
      accordance with these neuronal correlates gerbils learned to distinguish the
      directions of interval modulation within 3 days, but only with certain
      specifications.

PMID- 22387518
TI  - Neurotrauma and plasticity a conference of the German BMBF-research initiative.
AB  - A conference was held in Magdeburg, Germany on March 4?6 where experts discussed
      current research in neurotraumatology and neurop-sychological rehabilitation. A
      total of about 60 research projects of a nationwide program project funded by the
      German Ministry of Education and Research (BMBF) were presented in conjunction
      with projects from the BMBF-initiative program ?Neuropathology? of the Otto-v.
      Guericke University of Magdeburg and the Graduate Program in Neuroscience which
      were funded by the German Research Society (DFG) and the State of Sachsen-Anhalt.
      The scientific program ranges from molecular, cell biological, anatomical,
      physiological and behavioral analyses of secondary cell death, regeneration and
      plasticity to clinical outcome studies and epidemiological evaluations. As such,
      the conference provides a broad overview of German neuroscience in the areas of
      neurotrauma, rehabilitation and brain plasticity. The abstracts are part of a
      special issue of Restorative Neurology and Neuroscience on ?Neurotrauma and
      Neuropsychological Rehabilitation? which was published on the occasion of the
      conference.

PMID- 22387519
TI  - Production and immobilization of a novel thermoalkalophilic extracellular amylase
      from bacilli isolate.
AB  - A Thermoalkalophilic amylase was produced from an environmental bacterial
      isolate. The enzyme was then immobilized through its amino groups onto the epoxy
      rings of magnetic poly glycidyl methacrylate [m-poly (GMA)] beads. The free
      enzyme was active within a large pH range, between 7 and 12 and displayed the
      optimum activity at 95 degrees C and pH 10. The immobilization appeared to
      increase the stability of the enzyme as its bound form showed optimum activity at
      105 degrees C and pH 11.0. Kinetic studies demonstrated that immobilized enzyme
      had higher K(m) and lower V(max) values. The activity of the free and bound
      enzyme was determined, at 37 degrees C and pH 10.0 and pH 11.0, respectively, in
      the presence of various organic solvents and detergents (5%, v/v). Results
      obtained indicated that detergents, sodium dodecyl sulfate (SDS) and TritonX-100,
      caused six fold increase and that various organic solvents also increased the
      activity of the amylase.

PMID- 22387521
TI  - Availability, accessibility and promotion of smokeless tobacco in a low-income
      area of Mumbai.
AB  - OBJECTIVE: To examine the role of accessibility, product availability, promotions
      and social norms promotion, factors contributing to the use of smokeless tobacco
      (ST) products in a typical low-income community of Mumbai community using
      Geographic Information System (GIS), observational and interview methodologies
      and to assess implementation of Cigatettes and other Tobacco Products Act (COTPA)
      legislation. RATIONALE: In India, the third largest producer of tobacco in the
      world, smokeless tobacco products are used by men, women and children. New forms
      of highly addictive packaged smokeless tobacco products such as gutkha are
      inexpensive and rates of use are higher in low-income urban communities. These
      products are known to increase rates of oral cancer and to affect reproductive
      health and fetal development. METHODS: The study used a mixed methods approach
      combining ethnographic and GIS mapping, observation and key informant interviews.
      Accessibility was defined as density, clustering and distance of residents and
      schools to tobacco outlets. Observation and interview data with shop owners and
      community residents produced an archive of products, information on shop
      histories and income and normative statements. RESULTS: Spatial analysis showed
      high density of outlets with variations across subcommunities. All residents can
      reach tobacco outlets within 30-100 feet of their homes. Normative statements
      from 55 respondents indicate acceptance of men's, women's and children's use, and
      selling smokeless tobacco is reported to be an important form of income
      generation for some households. Multilevel tobacco control and prevention
      strategies including tobacco education, community norms change, licensing and
      surveillance and alternative income generation strategies are needed to reduce
      accessibility and availability of smokeless tobacco use.

PMID- 22387522
TI  - Short- and long-term morbidity and outcomes after robotic surgery for
      comprehensive endometrial cancer staging.
AB  - OBJECTIVE: Although intra-operative and immediate postoperative complications of
      robotic surgery are relatively low, little is known about long-term morbidity. We
      set out to assess both short- and long-term morbidities after robotic surgery for
      endometrial cancer staging. METHODS: All patients who underwent robotic staging
      for EMCA between 2006 and 2009 from two institutions were identified. Patient
      charts were retrospectively reviewed for surgical complications and postoperative
      morbidities. RESULTS: Five hundred three patients were identified. No differences
      in complication rates were found between 2006-2007 and 2008-2009, even though the
      median BMI increased from 29.9 (range 19-52) to 32 (range 17-70) (p=0.03). 6.4%
      of cases were converted to laparotomy. Median length of stay was one day (range 1
      46). No cystotomies, two enterotomies, one ureteric injury, and five vessel
      injuries occurred (1.6% intra-operative complications). Thirty-eight (7.6%)
      patients developed major postoperative complications, 11 (2.2%) had wound
      infections, and 15 (3%) required a transfusion in the 30-day peri-operative
      period. The total venous thromboembolism (VTE) rate for robotic cases was 1.7%.
      Partial cuff dehiscence managed conservatively occurred in 5 (1%) and complete
      dehiscence requiring closure in 7 (1.4%) patients; Sixty-three (13.4%) patients
      who had robotic staging developed lymphedema, with 40 (8%) requiring physical
      therapy. CONCLUSIONS: This study provides one of the largest cohorts of patients
      with robotic-assisted hysterectomy and lymphadenectomy (in 92.6%) with an
      assessment of morbidity. Our data demonstrates that robotic surgical staging can
      be safely performed with a low risk of short-term complications and lymphedema is
      the most frequent long-term morbidity.

PMID- 22387523
TI  - Random comparison of repeated faecal immunochemical testing at different
      intervals for population-based colorectal cancer screening.
AB  - OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests
      (FITs) requires successive screening rounds for an optimal preventive effect.
      However, data on the influence of the length of the screening interval on
      participation and diagnostic yield are lacking. Repeated FIT screening was
      therefore performed in a population-based trial comparing various repeat
      intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected
      and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration
      >= 50 ng/ml, corresponding to 10 MUg Hb/g faeces) with intervals of 1 (group I),
      2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7%
      in the first screening round and 63.2% in the second. The corresponding
      percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%.
      Triennial screening resulted in a higher participation rate in the second
      screening round compared with annual screening (p=0.04). The overall positivity
      rate in the second screening round was significantly lower compared with the
      first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on
      interval length (p=0.23). Similarly, the overall detection rate of advanced
      neoplasia was significantly lower in the second round compared with the first
      screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not
      depend on interval length (p=0.62). The positive predictive value of the FIT did
      not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total
      number of advanced neoplasia found at repeat FIT screening is not influenced by
      the interval length within a range of 1-3 years. Furthermore, there is a stable
      and acceptably high participation in the second screening round. This implies
      that screening intervals can be tailored to local resources.

PMID- 22387524
TI  - TLR4 stresses the liver.

PMID- 22387525
TI  - The central role of the c-Met pathway in rebuilding the liver.

PMID- 22387526
TI  - Factors affecting outcomes in Crohn's disease over 15 years.

PMID- 22387527
TI  - Direction of the brain--gut pathway in functional gastrointestinal disorders.

PMID- 22387528
TI  - Acute upper gastrointestinal bleeding: identifying low risk patients.

PMID- 22387529
TI  - Insulin resistance and response to telaprevir plus peginterferon alpha and
      ribavirin in treatment-naive patients infected with HCV genotype 1.
AB  - OBJECTIVE: Insulin resistance is a predictor of poor response to
      peginterferon/ribavirin in patients infected with the chronic hepatitis C virus
      (HCV). There are no data on direct-acting antivirals. This exploratory analysis
      assessed the effect of metabolic factors and insulin resistance, measured by
      homoeostatic model assessment (HOMA), on virological response to telaprevir in
      Study C208. DESIGN: Overall, 161 HCV genotype 1-infected, treatment-naive
      patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36
      weeks of peginterferon/ribavirin depending on on-treatment response criteria. The
      prognostic significance of several factors, including HOMA-insulin resistance
      (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24
      weeks after treatment was explored by multiple regression analysis. RESULTS:
      Baseline HOMA-IR data were available for 147 patients; baseline characteristics
      were consistent with the overall population. Baseline HOMA-IR <2, 2-4 and >4 was
      seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any
      time point) nor week 4 viral load decline were significantly influenced by
      baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density
      lipoprotein cholesterol level were predictive of sustained virological response
      (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was
      significantly lower in patients with sustained virological response than in those
      without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05).
      CONCLUSION: In this study, baseline HOMA-IR was not predictive of virological
      response to telaprevir in HCV genotype 1-infected, treatment-naive patients,
      while sustained virological response was associated with improved HOMA-IR. These
      results suggest that metabolic factors and insulin resistance do not have a
      significant effect on telaprevir-based treatment efficacy.

PMID- 22387530
TI  - Nerve activity recordings in routine human intestinal biopsies.
AB  - BACKGROUND: Most direct understanding of enteric nerve (patho)physiology has been
      obtained by electrode and imaging techniques in animal models and human surgical
      samples. Until now, neuronal activity recordings from a more accessible human
      tissue source have remained a true challenge. OBJECTIVES: To record nerve
      activity in human intestinal biopsies using imaging techniques. DESIGN: Submucous
      plexus was isolated from duodenal biopsies. Enteric nerves were functionally and
      morphologically examined using calcium (Ca(2+)) imaging and immunohistochemistry.
      Exogenous application of high-K(+) solution, the nicotinic cholinergic receptor
      agonist (1,1-dimethyl-4-phenylpiperazinium; DMPP) or serotonin (5-HT), and
      electrical stimulation of interganglionic fibre tracts were used to activate the
      neurons, and intracellular Ca(2+) concentrations ([Ca(2+)](i)) were monitored.
      Enteric ganglia were stained with neuronal and glial markers. RESULTS: Using high
      K(+) solution, 146 neurons were identified in 70 ganglia (44 biopsies from 29
      subjects). The exogenous application of DMPP or 5-HT caused a transient
      [Ca(2+)](i) increase, respectively, in 68% and 63% of the neurons identified by
      high-K(+). Electrical stimulation evoked responses in 57% of the neurons; these
      responses were totally or partly suppressed by tetrodotoxin or zero-Ca(2+)
      solution, respectively. Immunohistochemical analysis showed both isolated neurons
      and ganglia interconnected by typical interganglionic fibre bundles. The average
      number of ganglia was 7.7+/-6.0 per biopsy and each ganglion contained on average
      4.5+/-1.2 neurons. CONCLUSION: In this study, for the first time, live recordings
      were performed of nerve activity in intestinal biopsies. This novel approach is
      of key importance to study living neurons in both health and disease and to test
      newly developed compounds in an in-vitro human tissue model.

PMID- 22387531
TI  - Age- and oxidative stress-induced DNA damage in Drosophila intestinal stem cells
      as marked by Gamma-H2AX.
AB  - A decline in stem cell function is considered as a major cause of tissue atrophy,
      organ-system failure, cancer development and aging process. For a better
      understanding of the mechanism underlying age-related decline of stem cell
      function, characterization of aged stem cells is required. DNA damage induces
      epigenetic modifications that are associated with cell dysfunction. In mammals,
      gammaH2AX has been shown as DNA damage marker and an adaptor for recruiting
      chromatin modifying factors. In current study, utilizing a well-accepted
      Drosophila midgut model for stem-cell biology, we demonstrated aging- and
      oxidative stress-related accumulation of gammaH2AvD foci, analogous to mammal
      gammaH2AX, in Drosophila intestinal stem cells (ISCs), and obtained evidence that
      the changes in gammaH2AvD is closely associated with gamma-ray-induced DNA damage
      in ISCs and age-related accumulation of 8-oxo-2'-deoxyguanosine. The significance
      of our study is to document the first direct evidence for the accumulation of age
      related DNA-damage in ISCs, and to show gammaH2AvD as a useful biomarker in
      exploring the molecular mechanisms underlying stem cell aging in the Drosophila
      midgut.

PMID- 22387533
TI  - Phylogeographic relationships among Asian eggplants and new perspectives on
      eggplant domestication.
AB  - The domestication history of eggplant (Solanum melongena L.) has long been
      debated, with studies unable to narrow down where domestication occurred within a
      broad region of tropical Asia. The most commonly hypothesized region is India,
      however China has an equally old written record of eggplant use dating ca. 2000
      years before present. Both regions have a high diversity of landraces and
      populations of putatively wild eggplant: Solanum incanum L. in India and Solanum
      undatum Lam. in SE Asia. An additional complication is that there is taxonomic
      confusion regarding the two candidate progenitors. Here, we synthesize historic,
      morphologic, and molecular data (nrITS sequence and AFLP) to interpret the
      phylogeographic relationships among candidate progenitors and Asian eggplant
      landraces in order to test theories of domestication. A minimum of two
      domestication events is supported: one in India and one in southern China/SE
      Asia. Results also support separate domestication of S. melongena subsp.
      ovigerum, a group of morphologically distinct eggplants found in SE Asia, and
      suggest Asian S. incanum and S. undatum may not be genetically distinct. Routes
      of the spread of eggplant cultivation throughout Asia are proposed, and
      evolutionary relationships among allied species are discussed.

PMID- 22387532
TI  - Chronic intermittent ethanol and withdrawal differentially modulate basolateral
      amygdala AMPA-type glutamate receptor function and trafficking.
AB  - The amygdala plays a critical role in the generation and expression of anxiety
      like behaviors including those expressed following withdrawal (WD) from chronic
      intermittent ethanol (CIE) exposure. In particular, the BLA glutamatergic system
      controls the expression of both innate and pathological anxiety. Recent data
      suggests that CIE and WD may functionally alter this system in a manner that
      closely parallels memory-related phenomena like long-term potentiation (LTP). We
      therefore specifically dissected CIE/WD-induced changes in glutamatergic
      signaling using electrophysiological and biochemical approaches with a particular
      focus on the plasticity-related components of this neurotransmitter system. Our
      results indicate that cortical glutamatergic inputs arriving at BLA principal via
      the external capsule undergo predominantly post-synaptic alterations in AMPA
      receptor function following CIE and WD. Biochemical analysis revealed treatment
      dependent changes in AMPA receptor surface expression and subunit phosphorylation
      that are complemented by changes in total protein levels and/or phosphorylation
      status of several key, plasticity-associated protein kinases such as
      calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C
      (PKC). Together, these data show that CIE- and WD-induced changes in BLA
      glutamatergic function both functionally and biochemically mimic plasticity
      related states. These mechanisms likely contribute to long-term increases in
      anxiety-like behavior following chronic ethanol exposure.

PMID- 22387534
TI  - Development of phylogenetic markers from single-copy nuclear genes for multi
      locus, species level analyses in the mint family (Lamiaceae).
AB  - The use of single copy nuclear markers is of increasing importance in plant
      phylogenetics. The generally higher level of variability compared to chloroplast
      DNA and the ability to use incongruence in a multilocus analysis to determine
      reticulation patterns makes these kinds of sequence based markers especially
      useful for species level investigations. However, the prevalence of gene
      duplication that results from the high frequency of polyploidization events
      during the evolution of higher plants can impede marker development especially
      for groups lacking model organisms. Here, we present the strategy and results of
      marker development for phylogenetic analysis in Micromeria, using publicly
      available DNA sequences and ESTs from related genera from Lamiaceae, subfamily
      Nepetoideae. By eliminating markers with signatures of duplication during four
      steps of marker development, we were able to select 19 primer pairs that resulted
      in orthologous products for all the species studied. This corresponds to 23% of
      the initial 84 primer pairs designed. Using an initial sampling of eight
      individuals, we tested the markers for support of phylogenetic hypotheses related
      to the evolution of Micromeria on the Canary Islands. While some hypotheses were
      supported by all markers, an east west split, with a closer relationship between
      the species of Tenerife and Madeira on one hand and the ones from Gran Canaria
      and the eastern islands on the other is supported by 12 markers but contradicted
      by the remaining seven. This indicates that reticulation and inter-island gene
      flow played a role in the evolution of Micromeria.

PMID- 22387535
TI  - Double-edged sword effect of biochanin to inhibit nuclear factor kappaB:
      suppression of serine/threonine and tyrosine kinases.
AB  - Several protein tyrosine kinase (PTK) inhibitors predominantly isoflavones, such
      as genistein, erbstatin, quercetin, daidzein, present in red clover, cabbage and
      alfalfa, show apoptotic effect against cancer cells. In this study I found that
      biochanin, a methoxy form of genistein, inhibits IL-8-mediated activation of
      nuclear transcription factor kappaB (NF-kappaB) and activator protein 1 (AP-1)
      more potently than genistein as shown in Jurkat T-cell line. Both biochanin and
      genistein potently inhibited activity of Lck and Syk, but biochanin specifically
      inhibited activity of IKK. Biochanin inhibited completely NF-kappaB activation
      induced by PMA, LPS, pervanadate (PV), or H2O2, but only partially that induced
      by TNFalpha. Genistein was unable to inhibit IL-8-induced IKK activity, but it
      blocked PV-induced IKK activity. Biochanin inhibited activation of NF-kappaB by
      TRAF6 completely, but by TRAF2 partially. In silico data suggested that biochanin
      interacted strongly with serine/threonine kinase than genistein, though both
      equally interacted with PTK. The data show that both biochanin and genistein are
      potent inhibitors of PTK, but biochanin is a potent inhibitor of serine/threonine
      kinase too. Formononetin, having hydroxyl methoxy group is less potent to inhibit
      IKK than biochanin. Biochanin inhibits NF-kappaB activation not only by blocking
      the upstream IKK, but also PTK that phosphorylate tyrosine residues of
      IkappaBalpha. Thus, the double-edged sword effect of inhibition of NF-kappaB via
      inhibition of both serine/threonine kinase and PTK by biochanin might show useful
      therapeutic value against activities of cells that lead to tumorigenesis and
      inflammation.

PMID- 22387536
TI  - Kinetic stabilization of microtubule dynamics by indanocine perturbs EB1
      localization, induces defects in cell polarity and inhibits migration of MDA-MB
      231 cells.
AB  - Cell motility is an essential aspect of metastatic spread of cancer. Microtubule
      targeted agents exhibit anti-metastatic properties, the underlying mechanism of
      which remains understudied. In this study, we have investigated the role of
      microtubule dynamics in migration of cancer cells using indanocine, a synthetic
      small molecule inhibitor of tubulin. We found that indanocine, at concentrations
      that did not visibly affect microtubule organization, suppressed dynamic
      instability of microtubules and reduced the rate of migration of highly
      metastatic MDA-MB-231 cells. Indanocine-treated cells were defective in
      lamellipodium formation and could not develop polarized morphology. The kinetic
      stabilization of microtubules was associated with a marked increase in their
      acetylation level and a perturbation in the localization of EB1, a microtubule
      plus end binding protein. Using standard scratch wound healing assay and
      immunofluorescence analysis; we found that microtubule acetylation occurred in
      the direction of migration in vehicle-treated cells, whereas indanocine treatment
      led to a global acetylation of microtubules. The results together suggested that
      selective stabilization of microtubules was perturbed in the presence of
      indanocine that possibly resulted in lack of cell polarization and a concurrent
      reduction in migration of cells. Moreover, microtubule stabilization by
      indanocine affected adhesion turnover and impaired the polarized pattern of
      adhesion sites in cells. Together the results indicated that the regulation of
      microtubule dynamics is required to coordinate cell polarization as well as
      adhesion asymmetry and support the hypothesis that the perturbation of
      microtubule dynamics by tubulin-targeted agents can be exploited to restrict the
      migration of tumor cells.

PMID- 22387537
TI  - Characterization of cancer stem-like cells derived from a side population of a
      human gallbladder carcinoma cell line, SGC-996.
AB  - The cancer stem cell (CSC) hypothesis proposes that CSCs, which can renew
      themselves proliferate infinitely, and escape chemotherapy, become the root of
      recurrence and metastasis. Previous studies have verified that side population
      (SP) cells, characterized by their ability to efflux lipophilic substrate Hoechst
      33342, to share many characteristics of CSCs in multiplying solid tumors. The
      purpose of this study was to sort SP cells from a human gallbladder carcinoma
      cell line, SGC-996 and to preliminarily identify the biological characteristics
      of SP cells from the cell line. Using flow cytometry we effectively sorted SP
      cells from the cell line SGC-996. SP cells not only displayed higher
      proliferative, stronger clonal-generating, more migratory and more invasive
      capacities, but showed stronger resistance. Furthermore, our experiments
      demonstrated that SP cells were more tumorigenic than non-SP counterparts in
      vivo. Real-time PCR analysis and immunocytochemistry showed that the expression
      of ATP-binding cassette subfamily G member 2 (ABCG2) was significantly higher in
      SP cells. Hence, these results collectively suggest that SP cells are
      progenitor/stem-like cells and ABCG2 might be a candidate marker for SP cells in
      human gallbladder cancer.

PMID- 22387538
TI  - Combined treatment with fenretinide and indomethacin induces AIF-mediated, non
      classical cell death in human acute T-cell leukemia Jurkat cells.
AB  - Currently used cytotoxic drugs in cancer therapy have a similar mechanism of
      action and low specificity. Applied simultaneously, they show an additive effect
      with strong side effects. Clinical trials with the use of different agents in
      cancer therapy show that the use of these compounds alone is not very effective
      in fighting cancer. An alternative solution could be to apply a combination of
      these agents, because their combination has a synergistic effect on some cancer
      cells. Therefore, in our investigations we examined the effects of a synthetic
      retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug
      indomethacin on the process of apoptosis in the acute human T-cell leukemia cell
      line Jurkat. We demonstrate that treatment with the combination of the tested
      compounds induces the death of cells, that is peculiar and combines features of
      apoptosis as well as non-apoptotic cell death. In detail we observed, cell
      membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA
      fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF)
      nuclear translocation. Taken together these results indicate, that Jurkat cells
      after treatment with a combination of fenretinide and indomethacin undergo AIF
      mediated programmed cell death.

PMID- 22387539
TI  - Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat
      brain.
AB  - Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be
      implicated in the metabolism of bioactive peptides, including dynorphin 1-8,
      alpha-neoendorphin, beta-neoendorphin and GnRH. Furthermore, the higher levels of
      this peptidase are found in neuroendocrine tissue and testis. In the present
      study, we have evaluated the effect of acute cocaine administration in male rats
      on TOP specific activity and mRNA levels in prosencephalic brain areas related
      with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No
      significant differences on TOP specific activity were detected in the hippocampus
      and frontal cortex of cocaine treated animals compared to control vehicle group.
      However, a significant increase in activity was observed in the ventral striatum
      of cocaine treated-rats. The increase occurred in both, TOP specific activity and
      TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated
      in the processing of many neuropeptides, and previous studies have shown that
      cocaine also alters the gene expression of proenkephalin and prodynorphin in the
      striatum, the present findings suggest that TOP changes in the brain could play
      important role in the balance of neuropeptide level correlated with cocaine
      effects.

PMID- 22387540
TI  - Inhibition of LPS binding to MD-2 co-receptor for suppressing TLR4-mediated
      expression of inflammatory cytokine by 1-dehydro-10-gingerdione from dietary
      ginger.
AB  - Myeloid differentiation protein 2 (MD-2) is a co-receptor of toll-like receptor 4
      (TLR4) for innate immunity. Here, we delineated a new mechanism of 1-dehydro-10
      gingerdione (1D10G), one of pungent isolates from ginger (Zingiber officinale),
      in the suppression of lipopolysaccharide (LPS)-induced gene expression of
      inflammatory cytokines. 1D10G inhibited LPS binding to MD-2 with higher affinity
      than gingerol and shogaol from dietary ginger. Moreover, 1D10G down-regulated
      TLR4-mediated expression of nuclear factor-kappaB (NF-kappaB) or activating
      protein 1 (AP1)-target genes such as tumor necrosis factor alpha (TNF-alpha) and
      interleukin-1beta, as well as those of interferon (IFN) regulatory factor 3
      (IRF3)-target IFN-beta gene and IFN-gamma inducible protein 10 (IP-10) in LPS
      activated macrophages. Taken together, MD-2 is a molecular target in the anti
      inflammatory action of 1D10G.

PMID- 22387541
TI  - Rsf-1 is overexpressed in non-small cell lung cancers and regulates cyclinD1
      expression and ERK activity.
AB  - Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and
      associated with the malignant behavior of cancer cells. However, the expression
      of Rsf-1 in primary lung cancer and its biological roles in non-small cell lung
      cancer (NSCLC) have not been reported. The molecular mechanism of Rsf-1 in cancer
      aggressiveness remains ambiguous. In the present study, we analyzed the
      expression pattern of Rsf-1 in NSCLC tissues and found that Rsf-1 was
      overexpressed at both the mRNA and protein levels. There was a significant
      association between Rsf-1 overexpression and TNM stage (p=0.0220) and poor
      differentiation (p=0.0013). Furthermore, knockdown of Rsf-1 expression in H1299
      and H460 cells with high endogenous Rsf-1 expression resulted in a decrease of
      colony formation ability and inhibition of cell cycle progression. Rsf-1
      knockdown also induced apoptosis in these cell lines. Further analysis showed
      that Rsf-1 knockdown decreased cyclin D1 expression and phospho-ERK levels. In
      conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell
      growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic
      target in lung cancer.

PMID- 22387542
TI  - Rapamycin enhances docetaxel-induced cytotoxicity in a androgen-independent
      prostate cancer xenograft model by survivin downregulation.
AB  - BACKGROUND: Docetaxel is a first-line treatment choice in castration-resistant
      prostate cancer (CRPC). However, the management of CRPC remains an important
      challenge in oncology. There have been many reports on the effects of rapamycin,
      which is an inhibitor of the mammalian target of rapamycin (mTOR), in the
      treatment of carcinogenesis. We assessed the cytotoxic effects of the combination
      treatment of docetaxel and rapamycin in prostate cancer cells. Furthermore, we
      examined the relationship between these treatments and survivin, which is a
      member of the inhibitory apoptosis family. METHODS: Prostate cancer cells were
      cultured and treated with docetaxel and rapamycin. The effects on proliferation
      were evaluated with the MTS assay. In addition, we evaluated the effect on
      proliferation of the combination treatment induced knockdown of survivin
      expression by small interfering RNA transfection and docetaxel. Protein
      expression levels were assayed using western blotting. PC3 cells and xenograft
      growth in nude mice were used to evaluate the in vivo efficacy of docetaxel and
      its combination with rapamycin. RESULTS: In vitro and in vivo, the combination of
      rapamycin with docetaxel resulted in a greater inhibition of proliferation than
      treatment with rapamycin or docetaxel alone. In addition, in vitro and in vivo,
      rapamycin decreased basal surviving levels, and cotreatment with docetaxel
      further decreased these levels. Transfection siRNA against survivin enhanced the
      cytotoxicity of docetaxel in PC3 cells. CONCLUSION: The rapamycin-dependent
      enhancement of the cytotoxic effects of docetaxel was associated with the
      downregulation of survivin expression. Our results suggest that the combination
      of docetaxel and rapamycin is a candidate for the improved treatment of advanced
      prostate cancer.

PMID- 22387543
TI  - IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells,
      B cells and macrophages.
AB  - DNA demethylation has been found to occur at the promoters of a number of
      actively expressed cytokines and is believed to play a critical role in
      transcriptional regulation. While many DNA demethylation studies have focused on
      T cell activation, proliferation and differentiation, changes in DNA methylation
      in other types of immune cells are less well studied. We found that the
      expression of two cytokines (IL-2 and GM-CSF) responded differently to activation
      in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and
      MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level
      and at the promoters of the genes of these cytokines. The expression of several
      potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to
      be associated with immune cell activation.

PMID- 22387544
TI  - Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective
      antagonist inhibits angiogenesis.
AB  - Sphingosine 1-phosphate receptor type 1 (S1P(1)) was shown to be essential for
      vascular maturation during embryonic development and it has been demonstrated
      that substantial crosstalk exists between S1P(1) and other pro-angiogenic growth
      factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor. We developed a novel S1P(1)-selective antagonist, TASP0277308,
      which is structurally unrelated to S1P as well as previously described S1P(1)
      antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular
      responses, including migration and proliferation of human umbilical vein
      endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced
      tube formation in vitro and significantly suppressed tumor cell-induced
      angiogenesis in vivo. These findings revealed that S1P(1) is a critical component
      of VEGF-related angiogenic responses and also provide evidence for the efficacy
      of TASP0277308 for anti-cancer therapies.

PMID- 22387545
TI  - Role of soluble epoxide hydrolase phosphatase activity in the metabolism of
      lysophosphatidic acids.
AB  - The EPXH2 gene encodes for the soluble epoxide hydrolase (sEH), which has two
      distinct enzyme activities: epoxide hydrolase (Cterm-EH) and phosphatase (Nterm
      phos). The Cterm-EH is involved in the metabolism of epoxides from arachidonic
      acid and other unsaturated fatty acids, endogenous chemical mediators that play
      important roles in blood pressure regulation, cell growth, inflammation and pain.
      While recent findings suggested complementary biological roles for Nterm-phos,
      its mode of action is not well understood. Herein, we demonstrate that
      lysophosphatidic acids are excellent substrates for Nterm-phos. We also showed
      that sEH phosphatase activity represents a significant (20-60%) part of LPA
      cellular hydrolysis, especially in the cytosol. This possible role of sEH on LPA
      hydrolysis could explain some of the biology previously associated with the Nterm
      phos. These findings also underline possible cellular mechanisms by which both
      activities of sEH (EH and phosphatase) may have complementary or opposite roles.

PMID- 22387546
TI  - Mediation of glucolipotoxicity in INS-1 rat insulinoma cells by small heterodimer
      partner interacting leucine zipper protein (SMILE).
AB  - Sustained elevations of glucose and free fatty acid concentration have
      deleterious effects on pancreatic beta cell function. One of the hallmarks of
      such glucolipotoxicity is a reduction in insulin gene expression, resulting from
      decreased insulin promoter activity. Sterol regulatory element binding protein-1c
      (SREBP-1c), a lipogenic transcription factor, is related to the development of
      beta cell dysfunction caused by elevated concentrations of glucose and free fatty
      acid. Small heterodimer partner (SHP) interacting leucine zipper protein (SMILE),
      also known as Zhangfei, is a novel protein which interacts with SHP that mediates
      glucotoxicity in INS-1 rat insulinoma cells. Treatment of INS-1 cells with high
      concentrations of glucose and palmitate increased SREBP-1c and SMILE expression,
      and decreased insulin gene expression. Adenovirus-mediated overexpression of
      SREBP-1c in INS-1 cells induced SMILE expression. Moreover, adenovirus-mediated
      overexpression of SMILE (Ad-SMILE) in INS-1 cells impaired glucose-stimulated
      insulin secretion as well as insulin gene expression. Ad-SMILE overexpression
      also inhibited the expression of beta-cell enriched transcription factors
      including pancreatic duodenal homeobox factor-1, beta cell E box transactivator 2
      and RIPE3b1/MafA, in INS-1 cells. Finally, in COS-1 cells, expression of SMILE
      inhibited the insulin promoter activity induced by these same beta-cell enriched
      transcription factors. These results collectively suggest that SMILE plays an
      important role in the development of beta cell dysfunction induced by
      glucolipotoxicity.

PMID- 22387547
TI  - XPD could suppress growth of HepG2.2.15 and down-regulate the expression of
      hepatitis B virus x protein through P53 pathway.
AB  - OBJECTIVES: We investigated the effects of xeroderma pigmentosum D (XPD) on the
      growth of hepatoma cells and the expressions of P21, Bax, Bcl-2 and Hepatitis B
      virus X protein (HBx). In addition, we examined whether XPD affected the
      aforementioned genes via the P53 pathway. METHODS: Human hepatoma cells
      (HepG2.2.15) were transfected with XPD expression vector, followed by incubation
      with Pifithrin-alpha (P53 inhibitor). By using RT-PCR and Western blotting, the
      expression levels of XPD, P53, phospho-P53 (ser-15), P21, Bax, Bcl-2 and HBx were
      detected. The cell cycle and the apoptosis rate were examined with flow
      cytometry, and the cell viability was detected by MTT. RESULTS: Over-expression
      of XPD up-regulated the expressions of P53, phospho-P53 (ser-15), P21 and Bax but
      down-regulated the expressions of Bcl-2 and HBx. XPD inhibited the viability of
      HepG2.2.15 and exacerbated the apoptosis. However, the inhibition of P53 by
      Pifithrin-alpha abolished the above-mentioned effects of XPD. CONCLUSION: XPD
      could suppress growth of hepatoma cells, up-regulate the expressions of P21 and
      Bax, and down-regulate the expressions of Bcl-2 and HBx through the P53 pathway.
      There may be mutual influences among XPD, P53 and HBx that co-regulate
      hepatocarcinogenesis.

PMID- 22387548
TI  - Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes
      to growth inhibition and apoptosis in human bladder cancer T24 cells.
AB  - Ursolic acid (UA) has shown the anti-tumor properties against a number of human
      cancers both in vivo and in vitro, however, its effect in bladder cancer and the
      corresponding mechanisms of action remain largely unknown. Here we found that UA
      dose-dependently induced growth inhibition and apoptosis in human bladder cancer
      T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute
      to the process. Our Western-blot results demonstrated a significant AMPK
      activation after UA treatment in T24 cells. Notably, knockdown of AMPKalpha by
      the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and
      apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect.
      We found the ceramide level was increased after UA treatment in T24 cells, and UA
      induced AMPK activation and T24 cell apoptosis were inhibited by ceramide
      synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell
      permeable short-chain ceramide (C6), suggesting that ceramide might serve as an
      upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c
      Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1)
      signaling to cause survivin down-regulation. Our study suggests that activation
      of AMPK by UA contributes to growth inhibition and apoptosis in human bladder
      cancer cells.

PMID- 22387549
TI  - Signaling through L-selectin mediates enhanced chemotaxis of lymphocyte subsets
      to secondary lymphoid tissue chemokine.
AB  - L-selectin functions as an important adhesion molecule that mediates tethering
      and rolling of lymphocytes by binding to high endothelial venule (HEV)-expressed
      ligands during recirculation. Subsequent lymphocyte arrest and transmigration
      require activation through binding of HEV-decorated homeostatic chemokines such
      as secondary lymphoid tissue chemokine (SLC; CCL21) to its counterreceptor, CCR7.
      Importantly, L-selectin also functions as a signaling molecule. In this study,
      signaling induced by ligation of L-selectin using mAb or endothelial cell
      expressed ligand significantly enhanced the chemotaxis of murine T cells and B
      cells to SLC but not to other homeostatic chemokines. Consistent with the
      expression levels of L-selectin in different lymphocyte subsets, L-selectin
      mediated enhancement of chemotaxis to SLC was observed for all naive lymphocytes
      and effector/memory CD8(+) T cells, whereas only a subpopulation of
      effector/memory CD4(+) T cells responded. During in vivo mesenteric lymph node
      migration assays, the absence of L-selectin on lymphocytes significantly
      attenuated both their ability to migrate out of the HEV and their chemotaxis away
      from the vessel wall. Notably, ligation of L-selectin and/or CCR7 did not result
      in increased CCR7 expression levels, internalization, or re-expression.
      Pharmacologic inhibitor studies showed that L-selectin-mediated enhanced
      chemotaxis to SLC required intact intracellular kinase function. Furthermore,
      treatment of lymphocytes with the spleen tyrosine kinase family inhibitor
      piceatannol reduced their ability to migrate across the HEV in peripheral lymph
      nodes. Therefore, these results suggest that "cross-talk" in the signaling
      pathways initiated by L-selectin and CCR7 provides a novel mechanism for
      functional synergy between these two molecules during lymphocyte migration.

PMID- 22387550
TI  - Spatial alterations between CD4(+) T follicular helper, B, and CD8(+) T cells
      during simian immunodeficiency virus infection: T/B cell homeostasis, activation,
      and potential mechanism for viral escape.
AB  - HIV/SIV infections induce chronic immune activation with remodeling of lymphoid
      architecture and hypergammaglobulinemia, although the mechanisms leading to such
      symptoms remain to be fully elucidated. Moreover, lymph nodes have been
      highlighted as a predilection site for SIV escape in vivo. Following 20 rhesus
      macaques infected with SIVmac239 as they progress from pre-infection to acute and
      chronic infection, we document for the first time, to our knowledge, the local
      dynamics of T follicular helper (T(FH)) cells and B cells in situ. Progression of
      SIV infection was accompanied by increased numbers of well-delineated follicles
      containing germinal centers (GCs) and T(FH) cells with a progressive increase in
      the density of programmed death-1 (PD-1) expression in lymph nodes. The rise in
      PD-1(+) T(FH) cells was followed by a substantial accumulation of Ki67(+) B cells
      within GCs. However, unlike in blood, major increases in the frequency of CD27(+)
      memory B cells were observed in lymph nodes, indicating increased turnover of
      these cells, correlated with increases in total and SIV specific Ab levels. Of
      importance, compared with T cell zones, GCs seemed to exclude CD8(+) T cells
      while harboring increasing numbers of CD4(+) T cells, many of which are positive
      for SIVgag, providing an environment particularly beneficial for virus
      replication and reservoirs. Our data highlight for the first time, to our
      knowledge, important spatial interactions of GC cell subsets during SIV
      infection, the capacity of lymphoid tissues to maintain stable relative levels of
      circulating B cell subsets, and a potential mechanism for viral reservoirs within
      GCs during SIV infection.

PMID- 22387551
TI  - Upregulated protein arginine methyltransferase 1 by IL-4 increases eotaxin-1
      expression in airway epithelial cells and participates in antigen-induced
      pulmonary inflammation in rats.
AB  - Protein arginine methyltransferases (PRMTs), catalyzing methylation of both
      histones and other cellular proteins, have emerged as key regulators of various
      cellular processes. This study aimed to identify key PRMTs involved in Ag-induced
      pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of
      PRMT1 in the IL-4-induced eosinophil infiltration process. E3 rats were i.p.
      sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The
      expressions of PRMT1-6, eotaxin-1, and CCR3 in lungs were screened by real-time
      quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT
      inhibitor) and small interfering RNA-PRMT1 were used to interrupt the function of
      PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI
      rats to observe the effects on inflammatory parameters. The results showed that
      PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and
      significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI
      1 and the knockdown of PRMT1 expression were able to downregulate the expressions
      of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells.
      Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary
      inflammation, reduce IL-4 production and humoral immune response, and abrogate
      eosinophil infiltration into the lungs. In summary, PRMT1 expression is
      upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of
      PRMT1 activity can abrogate IL-4-dependent eotaxin-1 production to influence the
      pulmonary inflammation with eosinophil infiltration. The findings may provide
      experimental evidence that PRMT1 plays an important role in asthma pathogenesis.

PMID- 22387552
TI  - Neutrophilic granulocytes modulate invariant NKT cell function in mice and
      humans.
AB  - Invariant NKT (iNKT) cells are a conserved alphabetaTCR(+) T cell population that
      can swiftly produce large amounts of cytokines, thereby activating other
      leukocytes, including neutrophilic granulocytes (neutrophils). In this study, we
      investigated the reverse relationship, showing that high neutrophil
      concentrations suppress the iNKT cell response in mice and humans. Peripheral
      Valpha14 iNKT cells from spontaneously neutrophilic mice produced reduced
      cytokines in response to the model iNKT cell Ag alpha-galactosyl ceramide and
      expressed lower amounts of the T-box transcription factor 21 and GATA3
      transcription factor than did wild-type controls. This influence was extrinsic,
      as iNKT cell transcription factor expression in mixed chimeric mice depended on
      neutrophil count, not iNKT cell genotype. Transcription factor expression was
      also decreased in primary iNKT cells from the neutrophil-rich bone marrow
      compared with spleen in wild-type mice. In vitro, the function of both mouse and
      human iNKT cells was inhibited by coincubation with neutrophils. This required
      cell-cell contact with live neutrophils. Neutrophilic inflammation in
      experimental peritonitis in mice decreased iNKT cell T-box transcription factor
      21 and GATA3 expression and alpha-galactosyl ceramide-induced cytokine production
      in vivo. This was reverted by blockade of neutrophil mobilization. Similarly,
      iNKT cells from the human peritoneal cavity expressed lower transcription factor
      levels during neutrophilic peritonitis. Our data reveal a novel regulatory axis
      whereby neutrophils reduce iNKT cell responses, which may be important in shaping
      the extent of inflammation.

PMID- 22387553
TI  - Downregulation of inflammatory microRNAs by Ig-like transcript 3 is essential for
      the differentiation of human CD8(+) T suppressor cells.
AB  - We have investigated the mechanism underlying the immunoregulatory function of
      membrane Ig-like transcript 3 (ILT3) and soluble ILT3Fc. microRNA (miRNA)
      expression profile identified genes that were downregulated in ILT3-induced human
      CD8(+) T suppressor cells (Ts) while upregulated in T cells primed in the absence
      of ILT3. We found that miR-21, miR-30b, and miR-155 target the 3'-untranslated
      region of genes whose expression was strongly increased in ILT3Fc-induced Ts,
      such as dual specificity phosphatase 10, B cell CLL/lymphoma 6, and suppressor of
      cytokine signaling 1, respectively. Transfection of miRNA mimics or inhibitors
      and site-specific mutagenesis of their 3'-untranslated region binding sites
      indicated that B cell CLL/lymphoma 6, dual specificity phosphatase 10, and
      suppressor of cytokine signaling 1 are direct targets of miR-30b, miR-21, and miR
      155. Primed CD8(+) T cells transfected with miR-21&30b, miR-21&155, or miR
      21&30b&155 inhibitors displayed suppressor activity when added to autologous CD3
      triggered CD4 T cells. Luciferase reporter assays of miR-21 and miR-155 indicated
      that their transcription is highly dependent on AP-1. Analysis of activated T
      cells showed that ILT3Fc inhibited the translocation to the nucleus of the AP-1
      subunits, FOSB and c-FOS, and the phosphorylation of ZAP70 and phospholipase C
      gamma 1. In conclusion, ILT3Fc inhibits T cell activation and induces the
      generation of Ts targeting multiple inflammatory miRNA pathways.

PMID- 22387554
TI  - Discovery of a novel Toxoplasma gondii conoid-associated protein important for
      parasite resistance to reactive nitrogen intermediates.
AB  - Toxoplasma gondii modifies its host cell to suppress its ability to become
      activated in response to IFN-gamma and TNF-alpha and to develop intracellular
      antimicrobial effectors, including NO. Mechanisms used by T. gondii to modulate
      activation of its infected host cell likely underlie its ability to hijack
      monocytes and dendritic cells during infection to disseminate to the brain and
      CNS where it converts to bradyzoites contained in tissue cysts to establish
      persistent infection. To identify T. gondii genes important for resistance to the
      effects of host cell activation, we developed an in vitro murine macrophage
      infection and activation model to identify parasite insertional mutants that have
      a fitness defect in infected macrophages following activation but normal invasion
      and replication in naive macrophages. We identified 14 independent T. gondii
      insertional mutants out of >8000 screened that share a defect in their ability to
      survive macrophage activation due to macrophage production of reactive nitrogen
      intermediates (RNIs). These mutants have been designated counter-immune mutants.
      We successfully used one of these mutants to identify a T. gondii cytoplasmic and
      conoid-associated protein important for parasite resistance to macrophage RNIs.
      Deletion of the entire gene or just the region encoding the protein in wild-type
      parasites recapitulated the RNI-resistance defect in the counter-immune mutant,
      confirming the role of the protein in resistance to macrophage RNIs.

PMID- 22387555
TI  - Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient
      mice lead to marginally enhanced development of autoimmune encephalomyelitis.
AB  - EBV-induced gene 3 (EBI3)-encoded protein can form heterodimers with IL-27P28 and
      IL-12P35 to form IL-27 and IL-35. IL-27 and IL-35 may influence autoimmunity by
      inhibiting Th17 differentiation and facilitating the inhibitory roles of Foxp3(+)
      regulatory T (Treg) cells, respectively. In this study, we have evaluated the
      development of experimental autoimmune encephalomyelitis (EAE) in EBI3-deficient
      mice that lack both IL-27 and IL-35. We found that myelin oligodendrocyte
      glycoprotein peptide immunization resulted in marginally enhanced EAE development
      in EBI3-deficient C57BL6 and 2D2 TCR-transgenic mice. EBI3 deficiency resulted in
      significantly increased Th17 and Th1 responses in the CNS and increased T cell
      production of IL-2 and IL-17 in the peripheral lymphoid organs. EBI3-deficient
      and -sufficient 2D2 T cells had equal ability in inducing EAE in Rag1(-/-) mice;
      however, more severe disease was induced in EBI3(-/-)Rag1(-/-) mice than in Rag1(
      /-) mice by 2D2 T cells. EBI3-deficient mice had increased numbers of
      CD4(+)Foxp3(+) Treg cells in peripheral lymphoid organs. More strikingly, EBI3
      deficient Treg cells had more potent suppressive functions in vitro and in vivo.
      Thus, our data support an inhibitory role for EBI3 in Th17, Th1, IL-2, and Treg
      responses. Although these observations are consistent with the known functions of
      IL-27, the IL-35 contribution to the suppressive functions of Treg cells is not
      evident in this model. Increased Treg responses in EBI3(-/-) mice may explain why
      the EAE development is only modestly enhanced compared with wild-type mice.

PMID- 22387556
TI  - Actin reorganization is required for the formation of polarized B cell receptor
      signalosomes in response to both soluble and membrane-associated antigens.
AB  - B cells encounter both soluble Ag (sAg) and membrane-associated Ag (mAg) in the
      secondary lymphoid tissue, yet how the physical form of Ag modulates B cell
      activation remains unclear. This study compares actin reorganization and its role
      in BCR signalosome formation in mAg- and sAg-stimulated B cells. Both mAg and sAg
      induce F-actin accumulation and actin polymerization at BCR microclusters and at
      the outer rim of BCR central clusters, but the kinetics and magnitude of F-actin
      accumulation in mAg-stimulated B cells are greater than those in sAg-stimulated B
      cells. Accordingly, the actin regulatory factors, cofilin and gelsolin, are
      recruited to BCR clusters in both mAg- and sAg-stimulated B cells but with
      different kinetics and patterns of cellular redistribution. Inhibition of actin
      reorganization by stabilizing F-actin inhibits BCR clustering and tyrosine
      phosphorylation induced by both forms of Ag. Depolymerization of F-actin leads to
      unpolarized microclustering of BCRs and tyrosine phosphorylation in BCR
      microclusters without mAg and sAg, but with much slower kinetics than those
      induced by Ag. Therefore, actin reorganization, mediated via both polymerization
      and depolymerization, is required for the formation of BCR signalosomes in
      response to both mAg and sAg.

PMID- 22387557
TI  - Escape from CD8(+) T cell responses in Mamu-B*00801(+) macaques differentiates
      progressors from elite controllers.
AB  - A small number of HIV-infected individuals known as elite controllers experience
      low levels of chronic phase viral replication and delayed progression to AIDS.
      Specific HLA class I alleles are associated with elite control, implicating
      CD8(+) T lymphocytes in the establishment of these low levels of viral
      replication. Most HIV-infected individuals that express protective HLA class I
      alleles, however, do not control viral replication. Approximately 50% of Mamu
      B*00801(+) Indian rhesus macaques control SIVmac239 replication in the chronic
      phase in a manner that resembles elite control in humans. We followed both the
      immune response and viral evolution in SIV-infected Mamu-B*00801(+) animals to
      better understand the role of CD8(+) T lymphocytes during the acute phase of
      viral infection, when viral control status is determined. The virus escaped from
      immunodominant Vif and Nef Mamu-B*00801-restricted CD8(+) T lymphocyte responses
      during the critical early weeks of acute infection only in progressor animals
      that did not control viral replication. Thus, early CD8(+) T lymphocyte escape is
      a hallmark of Mamu-B*00801(+) macaques who do not control viral replication. By
      contrast, virus in elite controller macaques showed little evidence of variation
      in epitopes recognized by immunodominant CD8(+) T lymphocytes, implying that
      these cells play a role in viral control.

PMID- 22387558
TI  - Cutting edge: nitrogen bisphosphonate-induced inflammation is dependent upon mast
      cells and IL-1.
AB  - Nitrogen-containing bisphosphonates (NBPs) are taken by millions for bone
      disorders but may cause serious inflammatory reactions. In this study, we used a
      murine peritonitis model to characterize the inflammatory mechanisms of these
      agents. At dosages comparable to those used in humans, injection of NBPs into the
      peritoneum caused recruitment of neutrophils, followed by an influx of monocytes.
      These cellular changes corresponded to an initial increase in IL-1alpha, which
      preceded a rise in multiple other proinflammatory cytokines. IL-1R, IL-1alpha,
      and IL-1beta were required for neutrophil recruitment, whereas other MyD88
      dependent signaling pathways were needed for the monocyte influx. Mice deficient
      in mast cells, but not mice lacking lymphocytes, were resistant to NBP-induced
      inflammation, and reconstitution of these mice with mast cells restored
      sensitivity to NBPs. These results document the critical role of mast cells and
      IL-1 in NBP-mediated inflammatory reactions.

PMID- 22387560
TI  - Reaction-based colorimetric cyanide chemosensors: rapid naked-eye detection and
      high selectivity.
AB  - Taking advantages of both the well-known azobenzene structure and the special
      nucleophilicity of cyanide toward the acceptor moiety, a new ratiometric
      colorimetric chemodosimeter (Azo-1) toward cyanide anion was designed and
      synthesized by using intramolecular charge transfer (ICT) as a signaling
      mechanism. Upon the addition of CN(-) anion, the probe displayed apparent color
      changes from deep red to light yellow, which could be observed by naked eyes.
      With the aid of the UV-vis spectrometer, the detection limit could be as low as
      1.1 MUM. The probe possessed high selectivity for cyanide with respect to other
      common anions. In addition, Azo-1 could serve as practical colorimetric probe for
      "in-the-field" measurements that would not require any additional equipment by
      virtue of "dip-sticks" approach.

PMID- 22387561
TI  - Transient nerve root compression load and duration differentially mediate
      behavioral sensitivity and associated spinal astrocyte activation and mGLuR5
      expression.
AB  - Injury to the cervical nerve roots is a common source of neck pain. Animal models
      of nerve root compression have previously established the role of compression
      magnitude and duration in nerve root-mediated pain and spinal inflammation; yet,
      the response of the spinal glutamatergic system to transient nerve root
      compression and its relationship to compression mechanics have not been studied.
      The glutamate receptor, mGluR5, has a central role in pain, and its expression by
      neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial
      signaling. This study quantified spinal GFAP and mGluR5 expression following
      nerve root compressions of different magnitudes and durations in the rat.
      Compression to the C7 nerve root was applied for a duration that was either above
      (10 min) or below (3 min) the critical duration for mediating afferent discharge
      rates during compression. To also test for the effect of the magnitude of the
      compression load, either a 10 gf or a 60 gf was applied to the nerve root for
      each duration. Mechanical allodynia was assessed, and the C7 spinal cord was
      harvested on day 7 for immunofluorescent analysis. Double labeling was used to
      localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven
      days after injury, 10 min of compression produced significantly greater
      behavioral sensitivity (P<0.001) and spinal GFAP expression (P=0.002) than 3 min
      of compression, regardless of the compression magnitude. Nerve root compression
      at 60 gf produced a significant increase (P<0.001) in spinal mGluR5 for both of
      the durations studied. There was no difference in the distribution of mGluR5
      between astrocytes and neurons following nerve root compression of any type. The
      glutamatergic and glial systems are differentially modulated by the mechanics of
      nerve root compression despite the known contribution of glia to pain through
      glutamatergic signaling.

PMID- 22387565
TI  - PVX-potyvirus synergistic infections differentially alter microRNA accumulation
      in Nicotiana benthamiana.
AB  - In comparison to single infections, co-infection of Nicotiana benthamiana with
      Potato virus X (PVX) and Potato virus Y (PVY) or Plum pox virus (PPV), resulted
      in increased systemic symptoms (synergism in pathology). Previous studies have
      shown that virus infections affected the accumulation of various microRNAs
      (miRNAs) and miRNA target genes. Our studies revealed that double infection by
      PVX and PVY or PPV that produced the most severe symptoms in N. benthamiana
      altered accumulation of miR156, 171, 398, and 168, and/or their target
      transcripts to a greater extent or in a different direction than single
      infections that produced milder symptoms. These findings indicate a differential
      effect on miRNA metabolism of the combined infection by two unrelated plant
      viruses, which may account in part for the severe symptoms caused by
      PVX/potyvirus-associated synergisms.

PMID- 22387566
TI  - The C-terminal region of the hepatitis B virus X protein is required for its
      stimulation of HBV replication in primary mouse hepatocytes.
AB  - Hepatitis B virus (HBV) infection is an important risk factor for hepatocellular
      carcinoma (HCC). The hepatitis B virus X protein (HBx), a multifunctional
      regulatory protein encoded by HBV, is known to be involved in stimulation of
      viral replication by modulating cell cycle status. HBx is required for maximal
      virus replication in plasmid-based replication assays in immortalized human liver
      HepG2 cells and in primary rat hepatocytes. Moreover, the C-terminal region of
      HBx is important for HBV replication in HepG2 cells. However, in normal
      hepatocytes, the region of HBx that is responsible for its effect on cell cycle
      regulation and HBV replication is unclear. We have demonstrated that HBx is
      similarly required for maximal HBV replication in primary mouse hepatocytes and
      that the C-terminus of HBx is essential for its ability to stimulate HBV
      replication by inducing quiescent hepatocytes to exit G0 phase of the cell cycle
      but stall in G1 phase. Our studies establish that primary mouse hepatocytes
      support HBx-dependent HBV replication, and provide further evidence for the
      effect of the C-terminal region of HBx on HBV infection and replication.

PMID- 22387567
TI  - Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment
      of secondary hyperparathyroidism in patients receiving haemodialysis: results of
      the IMPACT SHPT study.
AB  - BACKGROUND: Optimal treatment for secondary hyperparathyroidism (SHPT) has not
      been defined. The IMPACT SHPT (ClinicalTrials.gov identifier: NCT00977080) study
      assessed whether dose-titrated paricalcitol plus supplemental cinacalcet only for
      hypercalcaemia is superior to cinacalcet plus low-dose vitamin D in controlling
      intact parathyroid hormone (iPTH) levels in patients with SHPT on haemodialysis.
      METHODS: In this 28-week, multicentre, open-label Phase 4 study, participants
      were randomly selected to receive paricalcitol or cinacalcet plus low-dose
      vitamin D. Randomization and analyses were stratified by mode of paricalcitol
      administration [intravenous (IV) or oral]. The primary efficacy end point was the
      proportion of subjects who achieved a mean iPTH value of 150-300 pg/mL during
      Weeks 21-28. RESULTS: Of 272 subjects randomized, 268 received one or more dose
      of study drug; 101 in the IV and 110 in the oral stratum with two or more values
      during Weeks 21-28 were included in the primary analysis. In the IV stratum,
      57.7% of subjects in the paricalcitol versus 32.7% in the cinacalcet group (P =
      0.016) achieved the primary end point. In the oral stratum, the corresponding
      proportions of subjects were 54.4% for paricalcitol and 43.4% for cinacalcet (P =
      0.260). Cochran-Mantel-Haenszel analysis, controlling for stratum, revealed
      overall superiority of paricalcitol (56.0%) over cinacalcet (38.2%; P = 0.010) in
      achieving iPTH 150-300 pg/mL during Weeks 21-28. Hypercalcaemia occurred in 4
      (7.7%) and 0 (0%) of paricalcitol-treated subjects in the IV and oral strata,
      respectively. Hypocalcaemia occurred in 46.9% and 54.7% of cinacalcet-treated
      subjects in the IV and oral strata, respectively. CONCLUSION: Paricalcitol versus
      cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low
      incidence of hypercalcaemia.

PMID- 22387568
TI  - Transcription factor regulation by mechanical stress.
AB  - New technologies and interest in cell mechanics are generating exciting new
      discoveries about how material properties and forces affect biological structure
      and function. Mechanical forces are transduced via a variety of mechanisms,
      recently beginning to be revealed, into signals capable of altering cell function
      and structure. Responses to physical stimuli occur at multiple levels, from
      changes in the structures of single proteins to global cascades capable of
      altering cell proliferation and differentiation. This review describes recent
      findings in which physical stimuli were shown to modulate transcription factor
      activity, including that of armadillo/beta-catenin, serum response factor (SRF),
      yes-associated protein (YAP) and nuclear factor kappaB (NF-kappaB).

PMID- 22387569
TI  - Behavioral effects following repeated exposure to hexachloronaphthalene in rats.
AB  - Polychlorinated naphthalenes (PCNs), including hexachloronaphthalene (HxCN), are
      widespread global environmental contaminants. Our experiments were aimed at
      assessing HxCN effects on motor behavior, long-term memory, pain sensitivity,
      magnitude of stress-induced analgesia, auditory function and sensorimotor gating,
      following repeated intragastric administration (28 days) of HxCN at 0.3 and 1.0
      mg/kg body weight. Three weeks after the exposure termination, male Wistar rats
      were subjected to the neurobehavioral tests battery performed in the following
      order: open-field test, passive avoidance test, hot-plate test and acoustic
      startle response test. Repeated administration of HxCN induced disorders of
      motivational processes manifested by: anorectic effect caused by aphagia and
      adipsia; significantly reduced motor activity (hypokinesia); impaired long-term
      memory and acquired passive avoidance reaction; reduced pain threshold and
      shortened duration of anxiety reaction after pain stimulus (sensory neglect).
      Some of these neurobehavioral effects (impaired long-term memory, reduced pain
      threshold and stress-induced analgesia) were observed at 0.3 mgHxCN/kg body
      weight without any signs of overt toxicity. The outcome of our study shows that
      HxCN, like other compounds of the persistent organic pollutants (POPs) group,
      creates a potential risk of behavioral changes in the central nervous system in
      the general population as a result of environmental exposure.

PMID- 22387572
TI  - ACR-26: a novel nicotinic receptor subunit of parasitic nematodes.
AB  - Nematode nicotinic acetylcholine receptors are the targets for many effective
      anthelmintics, including those recently introduced into the market. We have
      identified a novel nicotinic receptor subunit sequence, acr-26, that is expressed
      in all the animal parasitic nematodes we examined from clades III, IV and V, but
      is not present in the genomes of Trichinella spiralis, Caenorhabditis elegans,
      Pristionchus pacificus and Meloidogyne spp. In Ascaris suum, ACR-26 is expressed
      on muscle cells isolated from the head, but not from the mid-body region.
      Sequence comparisons with other vertebrate and nematode subunits suggested that
      ACR-26 may be capable of forming a functional homomeric receptor; when acr-26
      cRNA was injected into Xenopus oocytes along with Xenopus laevis ric-3 cRNA we
      occasionally observed the formation of acetylcholine- and nicotine-sensitive
      channels. The unreliable expression of ACR-26 in vitro may suggest that
      additional subunits or chaperones may be required for efficient formation of the
      functional receptors. ACR-26 may represent a novel target for the development of
      cholinergic anthelmintics specific for animal parasites.

PMID- 22387570
TI  - Epidemiological models of Mycobacterium tuberculosis complex infections.
AB  - The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant
      tuberculosis in the first decade of the 21st century increased the importance of
      epidemiological models for the disease. Due to slow progression of tuberculosis,
      the transmission dynamics and its long-term effects can often be better observed
      and predicted using simulations of epidemiological models. This study provides a
      review of earlier study on modeling different aspects of tuberculosis dynamics.
      The models simulate tuberculosis transmission dynamics, treatment, drug
      resistance, control strategies for increasing compliance to treatment, HIV/TB co
      infection, and patient groups. The models are based on various mathematical
      systems, such as systems of ordinary differential equations, simulation models,
      and Markov Chain Monte Carlo methods. The inferences from the models are
      justified by case studies and statistical analysis of TB patient datasets.

PMID- 22387573
TI  - Targeted next generation sequencing reveals a novel intragenic deletion of the
      TPO gene in a family with intellectual disability.
AB  - BACKGROUNDS AND AIMS: Next generation sequencing (NGS) approaches have
      revolutionized the identification of mutations underlying genetic disorders. This
      technology is particularly useful for the identification of mutations in known
      and new genes for conditions with extensive genetic heterogeneity. In the present
      study we investigated a consanguineous Pakistani family with intellectual
      disability (ID). METHODS: Genotyping was carried out using 250k and 6k SNP
      microarrays in order to perform homozygosity mapping and copy number variation
      (CNV) analysis. Targeted NGS was performed to identify the genetic defect in this
      family. qPCR was performed to validate and confirm the NGS result. RESULTS:
      Homozygosity mapping positioned the causative defect on chromosome 2p25.3-p25.2.
      Subsequent targeted NGS revealed an intragenic deletion of five exons of the gene
      TPO. CONCLUSIONS: NGS is a powerful method to uncover submicroscopic structural
      variations. This result demonstrates that an unbiased screening approach such as
      NGS can help to identify even unexpected disease-causing mutations.

PMID- 22387574
TI  - Does flavor impact function? Potential consequences of polyphenol-protein
      interactions in delivery and bioactivity of flavan-3-ols from foods.
AB  - Astringency is a component of the overall flavor experienced when consuming
      polyphenol rich foods and beverages such as tea, wine, cocoa and select fruits.
      Following consumption, the astringent sensation results from the well documented
      ability of polyphenols to bind to salivary proline rich proteins (PRP) and
      facilitate their precipitation in the oral cavity. In a similar fashion,
      polyphenols are also known to non-specifically bind food and other biological
      proteins. While much is known regarding the polyphenol-protein interactions
      leading to astringency, significantly less information is available regarding the
      impact of these polyphenol-protein interactions with food or other biological
      proteins on relevant physiological outcomes. This paper focuses on the
      interactions between flavan-3-ols, one of the most abundant dietary polyphenol
      forms, with proteins in food, salivary PRP and other physiological proteins. The
      physiological implications of these interactions in food and through the gut will
      be discussed in relation to manipulation of flavan-3-ol bioavailability,
      metabolism and biological activities including inhibition of digestive enzymes in
      the gut.

PMID- 22387575
TI  - Flavor learning in weanling rats and its retention.
AB  - The present study examined whether weanling animals can acquire associative
      memory for reward and retain it several weeks later. Three-week-old Wistar male
      rats were trained in a flavor learning task. Half of the rats received
      unsweetened grape-flavored water on odd-numbered days and sweetened (sucrose)
      cherry-flavored solution on even-numbered days. The remaining rats received
      sweetened grape-flavored solution on odd-numbered days and unsweetened cherry
      flavored water on even-numbered days. During the acquisition session, the liquid
      was presented to each rat for 15 min daily for 6 consecutive days. In the
      following test session, each rat was presented with unsweetened cherry-flavored
      water and grape-flavored water simultaneously for 15 min daily for 4 consecutive
      days. The rats showed significant preferences for the flavor previously
      associated with 2% and 10% sucrose, significant aversion to the flavor associated
      with 30% sucrose, and no particular preference or aversion to the flavor
      associated with 20% sucrose, indicating a hedonic shift from positive to negative
      with an increasing concentration of sucrose. The association learning acquired at
      the age of 3 weeks was retained when re-tested in adulthood at the age of 20
      weeks. In contrast to the conditioned flavor aversion associated with 30%
      sucrose, 20-week-old rats showed a preference for this flavor. In accordance with
      these learning effects, 3-week-old rats preferred 2% sucrose to 30% sucrose, and
      the reverse was true in 20-week-old rats. The reasons for rejection of high
      concentration sucrose by weanling rats are also discussed. The present study
      showed that weanling rats established a conditioned flavor preference or aversion
      depending on the concentration of associated sucrose and retained it in
      adulthood, indicating that feeding experience in the weanling period is important
      in influencing later dietary preferences.

PMID- 22387576
TI  - Meta-regression analysis to indirectly compare prophylaxis with dalteparin or
      enoxaparin in patients at high risk for venous thromboembolic events.
AB  - BACKGROUND: Dalteparin and enoxaparin are recommended as thromboprophylaxis for
      at least 10 days in patients undergoing abdominal surgery (AS) or hospitalized
      patients with acute medical illnesses. Even though both agents have proven
      clinical effectiveness through randomized trials, there have been no head-to-head
      studies. In this evaluation, indirect statistical techniques were used to compare
      safety and efficacy between dalteparin and enoxaparin in these 2 high-risk
      patient populations. METHODS: A literature search was conducted from January 1980
      to November 2010 for randomized trials evaluating dalteparin or enoxaparin
      prophylaxis following AS or in hospitalized patients. Binary outcomes for safety
      and efficacy were statistically pooled using fixed or random effects models in
      cases of significant heterogeneity. In trials where a common control was used
      (eg, unfractionated heparin [UH]), indirect statistical comparisons between
      dalteparin and enoxaparin were performed using meta-regression analysis with
      active drug as the primary independent variable. RESULTS: The meta-analysis in AS
      patients showed that enoxaparin or dalteparin had comparable efficacy to UH in
      terms of venous thromboembolic events (VTEs; relative risk reduction [RR] = 0.87,
      P = .46). The indirect statistical comparison was unable to find significant
      differences between enoxaparin and dalteparin in terms of risk for VTE (P = .84),
      major bleeding (P = .38), heparin-induced thrombocytopenia ([HIT]; P = .084), or
      death (P = .97). In acutely ill medical patients, treatment with enoxaparin or
      dalteparin had a 52% VTE risk reduction compared to placebo (RR = 0.48, P <
      .001). The indirect comparison was also unable to find significant differences
      between enoxaparin and dalteparin in terms of VTEs (P = .15), major bleeds (P =
      .39), HIT (P = .48), and death (P = .41). CONCLUSIONS: The findings suggest
      comparable safety and efficacy between dalteparin and enoxaparin in AS and in
      acutely ill medical patients.

PMID- 22387578
TI  - AssessMent of ProphylAxis for VenouS ThromboembolIsm in hospitalized patients:
      the MASIH study.
AB  - BACKGROUND: Venous thromboembolism (VTE) accounts for several cases of in
      hospital mortality (over 100 000 deaths annually in the West). Despite the
      existence of effective prophylaxis guidelines for at-risk patients, the
      guidelines adherence is missing. METHODS: We evaluated the thromboprophylaxis
      reception and appropriateness based on the eighth edition of the American College
      of Chest Physicians (ACCP) guidelines on VTE prophylaxis, among hospitalized
      patients of a World Health Organization (WHO)-collaborating teaching hospital in
      a 3-month period. RESULTS: From the 904 evaluated cases, 481 entered the study.
      Appropriate decision on whether to prophylaxe or not, was made in 305 (63.40%),
      however, complete appropriateness (considering correct regimen type, dosing, and
      duration) was seen only in 229 patients (47.60%). The ACCP risk for VTE was the
      strongest predictor of thromboprophylaxis prescription (odds ratio [OR]: 2.62,
      95% confidence interval [CI]: 1.35-5.05). CONCLUSIONS: Our thromboprophylaxis
      results were comparable to that of Western countries. Improved thromboprophylaxis
      appropriateness, which requires improving the physicians' thromboprophylaxis
      awareness and knowledge, could reduce the rate of in-hospital VTE and translate
      into better patient care.

PMID- 22387577
TI  - Evaluation of the prothrombin time for measuring rivaroxaban plasma
      concentrations using calibrators and controls: results of a multicenter field
      trial.
AB  - This study evaluated the prothrombin time (PT) assay for the measurement of
      plasma concentrations of rivaroxaban using calibrators and controls. The intra-
      and interlaboratory precision of the measurement was investigated in a field
      trial involving 21 laboratories. Each laboratory was provided with rivaroxaban
      calibrators and control plasma samples containing different concentrations of
      rivaroxaban, and PT reagents. The evaluation was carried out over 2 consecutive
      weeks using centrally provided and local PT reagents. A calibration curve was
      produced each day (for inter-run precision), and day-to-day precision was
      evaluated by testing 3 control plasma samples. A large interlaboratory variation
      (in seconds) was observed with local PT reagents. The results were less variable
      when expressed as rivaroxaban concentrations (ng/mL) or when central PT reagent
      was used (STA Neoplastine CI Plus). The widely available PT assay, in conjunction
      with rivaroxaban calibrators, may be useful for the measurement of peak plasma
      levels of rivaroxaban.

PMID- 22387579
TI  - Impact of mean platelet volume on postinterventional TIMI flow in the acute
      myocardial infarction treated with primary coronary intervention.

PMID- 22387580
TI  - Effect of uremia and hemodialysis on platelet apoptosis.
AB  - The blood platelet proteome of hemodialyzed patients with uremia exhibits
      significant difference in comparison with the blood platelet proteome of healthy
      individuals. This alteration is manifested by the presence of high concentrations
      of low-molecular peptides within the whole range of isoelectric points. Increased
      platelet apoptosis has been put forward as a possible cause of this phenomenon.
      The aim of the present research was to assess whether blood platelet populations
      from hemodialyzed patients with uremia exhibit higher binding capacity of Annexin
      V than control samples from healthy donors. It was found that blood platelets of
      hemodialyzed patients, in the period between dialyses, bound significantly more
      Annexin V with no different incorporation of propidium iodide in comparison with
      platelets of control donors and conservatively treated patients with uremia. The
      results support the hypothesis that the process of hemodialysis may be at least
      partially responsible for triggering blood platelet apoptosis and result in
      increased risk of thrombosis.

PMID- 22387581
TI  - Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of
      antiphospholipid syndrome.
AB  - The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are
      directed at a number of phospholipid-binding proteins: beta2 glycoprotein I
      (beta2GPI), prothrombin, and so on. Antibodies directed at beta2GPI are accepted
      as a classification criterion for APS, while the presence of antiprothrombin
      antibodies is not. In the present article, we investigated the possible role of
      antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a
      cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS
      related diseases. We found aPS/PT to be highly associated with venous thrombosis
      (immunoglobulin G [IgG] aPS/PT odds ratio [OR], 7.44; 95% confidence interval
      [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric
      abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial
      thrombosis. A very high degree of concordance between the concentration of aPS/PT
      and lupus anticoagulant activity was demonstrated. Therefore, we support the
      inclusion of aPS/PT determination as second-level assay to confirm APS
      classification.

PMID- 22387582
TI  - The efficacy and safety of pharmacological prophylaxis of venous thromboembolism
      following elective knee or hip replacement:  systematic review and network meta
      analysis.
AB  - The present systematic review was conducted to assess the efficacy and safety of
      apixaban versus other anticoagulants, for the prevention of venous
      thromboembolism (VTE) following total hip replacement (THR) and total knee
      replacement (TKR) surgery. Electronic databases were interrogated to identify
      relevant randomized controlled trials. A series of direct/indirect comparisons
      and a network meta-analysis were conducted. Indirect comparisons found that the
      odds ratio of "all VTE and all-cause death" were significantly higher for
      dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95%
      confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42).
      Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR,
      0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No
      significant differences were observed in bleeding outcomes between treatments.
      The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated
      similar or improved efficacy and similar safety compared with current therapies
      in this indication.

PMID- 22387583
TI  - PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in
      the intensive care unit.
AB  - BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) may be
      challenging in critically ill patients, as heparin exposures are ubiquitous, and
      thrombocytopenia is common. Unwarranted ordering and incorrect interpretation of
      heparin antibody tests can expose a patient to adverse drug events and imposes a
      significant economic burden on our health care system. METHODS: A prospective,
      observational study was performed over 4 months on all adult patients located in
      5 intensive care units, with a heparin antibody test ordered. RESULTS: A platelet
      factor 4/heparin enzyme-linked immunosorbent assay (ELISA) test was ordered in
      131 patients. In total, 110 patients had a low 4Ts score (0-3), and of these 103
      had a negative ELISA result. In patients with a low 4Ts score, 0 (0%) of 110 had
      an optical density value >1.0. One hundred twenty-nine patients (98%) had another
      possible cause of thrombocytopenia identified. CONCLUSION: In critically ill
      patients, low 4Ts scores indicate a low probability of HIT, and heparin antibody
      testing in these patients is not useful.

PMID- 22387584
TI  - Novel oral anticoagulation in management of venous thromboembolism, atrial
      fibrillation, and acute coronary syndrome.
AB  - Venous thromboembolism (VTE) is a major public health concern since the incidence
      of VTE rises substantially with age. Furthermore, the diagnosis can be elusive
      since patients can present differently, causing delay in diagnosis and initiation
      of treatment and resulting in major morbidity and mortality. In addition to
      accuracy and precision in diagnosis, antithrombotic therapies are the
      cornerstones of VTE management. In traditional paradigm, vitamin K antagonists
      (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in
      management of VTE. Warfarin has been the only available oral anticoagulant
      therapy for several decades. Although warfarin is effective in both treatment and
      prophylaxis against VTE, there are several limitations. Therefore, the novel
      anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran
      etexilate, have apparent advantages over warfarin in terms of clinical efficacy
      and adverse effects. The objective of this review is to describe the background
      and clinical implications of these novel anticoagulants.

PMID- 22387585
TI  - Increase in mean platelet volume in patients with myocardial bridge.
AB  - AIM: Myocardial bridge is associated with atherosclerosis altered in shear stress
      and endothelial dysfunction. Mean platelet volume (MPV), a determinant of
      platelet activation, is shown to be related with atherosclerosis and endothelial
      dysfunction. In this study, we aimed to evaluate platelet function assessed by
      MPV in patients with myocardial bridge. METHODS: Forty-two patients with
      myocardial bridge in the left anterior descending artery (LAD) and 43 age- and
      gender-matched healthy participants were included in the study. Myocardial
      bridging was defined as an intramyocardial systolic compression or milking of a
      segment of an epicardial coronary artery on angiography. For the entire study
      population, MPV was measured using an automatic blood counter. RESULTS: The study
      population consisted of 42 patients with myocardial bridge (52.7 +/- 10.2, 76.2%
      male) and 43 age- and sex-matched healthy control participants (52.1 +/- 10.4,
      74.4% male). Compared to the control group, MPV value was significantly higher in
      patients with myocardial bridge (8.9 +/- 1.24 vs 8.3 +/- 0.78; P = .01). Further,
      there were no significant differences between groups regarding hemoglobin level,
      platelet count, fasting blood glucose, and creatinine levels. CONCLUSIONS: Our
      study findings indicated that myocardial bridge is associated with elevated MPV
      values. Our results might partly explain the increased cardiovascular events in
      patients with myocardial bridge.

PMID- 22387586
TI  - The significance of microthrombosis and fgl2 in no-reflow phenomenon of rats with
      acute myocardial ischemia/reperfusion.
AB  - No-reflow phenomenon due to cardiac microvascular dysfunction or disturbance
      aggravates clinic outcomes of a portion of patients with acute myocardial
      infarction undergoing percutaneous coronary intervention or thrombolytic therapy.
      Our working hypothesis was that cardiac microthrombosis would play an important
      role in the pathogenesis. We investigated that cardiac microthrombi were observed
      by Martius, Scarlet, Blue methocl (MSB) and Masson trichrome staining.
      Furthermore, we investigated the expression of fibrinogen-like protein 2 (fgl2)
      in rats with acute myocardial ischemia/reperfusion (MI/R) and its possible
      pathological and clinical significance. The fgl2 was highly expressed in
      myocardium of rats with acute MI/R and located at cardiac microvascular walls. We
      found that the expression of fgl2 in peripheral mononuclear cells of rats with
      acute MI/R significantly increased correspondingly with its cardiac expression.
      Expression of cardiac fgl2 was correlated with no-reflow size of rats with acute
      MI/R, which was detected and calculated by thioflavin S staining. No-reflow size
      was in line with cardiac diastolic dysfunction of rats with acute MI/R monitored
      by hemodynamics. Thus, microthrombosis is involved in cardiac microvascular
      dysfunction or disturbance of rats with acute MI/R as one cause, and fgl2 may
      emerge as a predictor of the occurrence of no-reflow phenomenon.

PMID- 22387587
TI  - Tolerogenic dendritic cells as a target for the therapy of immune
      thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease in which platelets are
      destroyed by special antiplatelet autoantibodies produced by B cells. Dendritic
      cells (DCs) are professional antigen-presenting cells involved in humoral
      immunity and cellular immunity and among them DCs that induce autoimmune
      tolerance are called tolerogenic DCs (tDCs). As a promising immunotherapeutic
      strategy for ITP, tDCs have received increasing attention. In this review, we
      describe the significant role of DCs in regulating autoimmune balances, introduce
      the manipulation strategies to generate tDCs, summarize recent progress on the
      experimental application of tDCs for ITP therapy, and finally discuss the
      perspectives of tolerogenic vaccination for ITP treatment in the clinic.

PMID- 22387588
TI  - Pathogen recognition receptors in channel catfish: II. Identification, phylogeny
      and expression of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs).
AB  - Vertebrates including teleost fish have evolved an array of pathogen recognition
      receptors (PRRs) for detecting and responding to various pathogen-associated
      molecular patterns (PAMPs), including Toll-like receptors (TLRs), nucleotide
      binding domain, leucine-rich repeat containing receptors (NLRs), and the retinoic
      acid inducible gene I (RIG-I) like receptors (RLRs). As a part of the series of
      studies targeted to characterize catfish PRRs, we described 22 NLR receptors in
      the sister contribution. Here in this study, we focused on cytosolic PRRs
      recognizing nucleotide pathogen-associated molecular patterns (PAMPs) of invading
      viruses, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR
      receptors). Three RLRs with DExD/H domain containing RNA helicases, retinoic acid
      inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and
      laboratory of genetics and physiology 2 (LGP2), were identified from channel
      catfish, Ictalurus punctatus. The catfish RIG-I encodes 937 amino acids that
      contains two CARDs, a DExDc, a HELICc and a RD domains. MDA5 encodes 1005 amino
      acids with all the domains identified for RIG-I. LGP2 encodes 677 amino acids
      that contain other domains but not the CARD domain at the N-terminus.
      Phylogenetic analyses of the three genes of catfish showed close clustering with
      their counterparts from other teleost fish. All the genes were found to be
      constitutively expressed in various tissues of catfish with minor variations.
      Channel catfish ovarian cells when infected with channel catfish virus showed
      significant increase in the transcript abundance of all the three genes. Further,
      RLR genes showed significant increases in expression in the liver tissue
      collected at different time-points after bacterial infection as well. The results
      indicate that the catfish RLRs may play important roles in antiviral and anti
      bacterial immune responses.

PMID- 22387589
TI  - Maternal immunity in fish.
AB  - Both innate and adaptive immune-relevant factors are transferred from mother to
      offspring in fishes. These maternally-transferred factors include IgM, lysozymes,
      lectin, cathelicidin and complement components. Recently, yolk proteins,
      phosvitin and lipovitellin, have been shown to be maternally-transferred factors,
      functioning in the defense of teleost larvae against pathogens. Among these
      factors, the mode of action of complement components and yolk proteins has been
      explored, whereas that of all the other factors remains elusive. At present, the
      transfer mechanisms of maternally-derived immune factors are largely unknown
      although those of IgM and yolk protein transmission from mother to offspring have
      been reported in some fishes. Maternal transfer of immunity is affected by many
      elements, including biological factors, such as age and maturation, and
      environmental conditions experienced by brood fish, such as pathogens and
      nutritional supply. Practically, the manipulation of maternal immunity transfer
      can be used to enhance the survival rate of fish larvae.

PMID- 22387590
TI  - Cloning and functional characterization of rat stimulator of interferon genes
      (STING) regulated by miR-24.
AB  - Stimulator of interferon (IFN) genes (STING), also known as
      MPYS/MITA/ERIS/TMEM173, is a recently discovered adaptor protein that functions
      downstream of RIG-I and upstream of TBK1 and plays an important role in type I
      interferon (IFN) production. Mammalian STINGs have been isolated from human,
      mouse, pig, cattle and chimpanzee. In this study, the rat STING cDNA was cloned
      by degenerate PCR and rapid amplification of 3'-cDNA ends (3'-RACE) strategies.
      The full-length cDNA of rat STING consists of 1615 bp with a 1140-bp open reading
      frame (ORF). The predicted protein is composed of 379 amino acids and contains 2
      putative transmembrane domains. The amino acid similarities between the STING
      from rat and other mammals range from 68% to 82%. Real-time quantitative PCR
      analysis indicated that rat STING mRNA was most abundant in the spleen, pancreas
      and lymph node. Overexpression of rat STING led to upregulation of IFN-beta mRNA
      expression in IEC-6 cells. Rat STING mRNA was up-regulated when IEC-6 cells were
      transfected with poly (I:C). In addition, a miR-24 binding site in the 3'UTR of
      rat STING was identified. We also found that endogenous STING could be regulated
      post-transcriptionally by miR-24 in IEC-6 cells. These results are of importance
      to reveal the biological function of STING in rat animal model.

PMID- 22387591
TI  - Psychiatric illness and behavioural problems in adults with learning disability
      and epilepsy.
AB  - We retrospectively collected data on the rate and type of psychiatric illness and
      behavioural problems on 143 adults with learning disability and epilepsy. 55%
      behavioural problems. 19% verbal aggression and temper tantrums, and 13%
      injurious behaviour. The overall rates of behavioural problems and different
      types of behaviours found in the current study cohort are similar to what was
      found before in learning disabled adults in general, as well as in epileptic and
      non-epileptic learning disabled adults. Psychiatric diagnosis was made in 12.6%
      combined diagnosis of schizophrenia, delusional disorder and schizo-affective
      disorder was most common (5%) diagnosis of depressive episode (3%) bipolar
      affective disorder.

PMID- 22387592
TI  - Speech impairment in a large sample of patients with Parkinson's disease.
AB  - This study classified speech impairment in 200 patients with Parkinson's disease
      (PD) into five levels of overall severity and described the corresponding type
      (voice, articulation, fluency) and extent (rated on a five-point scale) of
      impairment for each level. From two-minute conversational speech samples,
      parameters of voice, fluency and articulation were assessed by two trained
      raters. Voice was found to be the leading deficit, most frequently affected and
      impaired to a greater extent than other features in the initial stages.
      Articulatory and fluency deficits manifested later, articulatory impairment
      matching voice impairment in frequency and extent at the 'Severe' stage. At the
      final stage of 'Profound' impairment, articulation was the most frequently
      impaired feature at the lowest level of performance. This study illustrates the
      prominence of voice and articulatory speech motor control deficits, and draws
      parallels with deficits of motor set and motor set instability in skeletal
      controls of gait and handwriting.

PMID- 22387593
TI  - Decreased volume of the cerebral ventricles on CT images in Gilles de la
      Tourette's syndrome.
AB  - The aim of the present study was to estimate the volume of the ventricular system
      comprising lateral plus third ventricles in patients with Gilles de la Tourette's
      syndrome on computed tomographic (CT) scannings using unbiased stereological
      principles and to compare that volume with a control group. We found a
      significantly reduced ventricular volume in 24 patients with Gilles de la
      Tourette's syndrome (GTS) compared with 28 controls.

PMID- 22387594
TI  - Role of the striatum and the cerebellum in motor skill acquisition.
AB  - Motor skill acquisition was investigated in patients with Parkinson's disease
      (PD) or cerebellar dysfunction using two sensory-guided tracking tasks. The
      subjects had to learn to track a visual target (a square) on a computer screen by
      moving a joystick under two different conditions. In the unreversed task, the
      horizontal target movements were semi-predictable and could be anticipated. In
      the reversed task, the horizontal movements of a pointer which had to be kept
      within the target square were mirror-reversed to the joystick movements. PD
      patients showed intact learning of the semi-predictable task and reduced learning
      of the mirror-reversed task; patients with cerebellar dysfunction showed the
      opposite pattern. These findings are discussed in relation to the differential
      contribution of the cerebellum and the striatum to motor skill acquisition: the
      cerebellum appears to participate in the implementation of anticipatory
      movements, whereas the striatum may be critically involved in types of motor
      learning which require a high degree of internal elaboration.

PMID- 22387595
TI  - Self and body esteem perception in multiple sclerosis.
AB  - Self esteem and body esteem were examined in a group of 35 relapsing-remitting
      multiple sclerosis (MS) patients using the Body Esteem Scale (BES) and the
      Eysenck Self Esteem Scale (ESES) and compared to age and sex matched normal
      controls. There were 23 females and 12 males in the MS patient's group; average
      age 38.9 years (range: 22-52). All participants completed the self-rated BES
      evaluating the following subscales: females - sexual attractiveness, physical
      condition and weight concern; males - physical attractiveness, physical condition
      and upper body strength. In addition all participants were scored, following a
      semi-structured interview, on the ESES. Psychiatric co-morbidity was excluded
      using a semi-structured interview by the consulting psychiatrist. All evaluations
      were carried out during the remitting phase. Statistical analysis, comparing
      patients to healthy controls, demonstrated lowered self-rating of the physical
      condition (males < 0.05, females < 0.001). On the other hand, no significant
      differences were found in the physical (male) or sexual (female)?attractiveness
      subscales. The mean ESES score in the patients group was 23.2 +/- 4.0, slightly
      above the reported average. The controls mean ESES was 28.4 +/- 3.6, (P < 0.05).
      No correlation was found between self and body esteem amongst M.S. patients. This
      study emphasizes impaired perception of body esteem in multiple sclerosis
      patients even in remission. The preservation of physical and sexual
      attractiveness may be related to the non-disfiguring nature of the disease.
      Preservation of self-esteem in MS patients suggests that body-esteem should be
      the focus of supportive treatment.

PMID- 22387596
TI  - Storage of verbal associations is sufficient to activate the left medial temporal
      lobe.
AB  - Neuroimaging studies have shown that memory encoding activates the medial
      temporal lobe (MTL). Many believe that these activations are related to novelty
      but it remains unproven which is critical - novelty detection or the rich
      associative encoding it triggers. We examined MTL activation during verbal
      associative encoding using functional magnetic resonance imaging. First,
      associative encoding activated left posterior MTL more than single word encoding
      even though novelty detection was matched, indicating not only that associative
      encoding activates the MTL particularly strongly, but also that activation does
      not require novelty detection. Moreover, it remains to be convincingly shown that
      novelty detection alone does produce such activation. Second, repetitive
      associative encoding produced less MTL activation than initial associative
      encoding, indicating that priming of associative information reduces MTL
      activation. Third, re-encoding familiar associations in a well-established way
      had a minimal effect on both memory and MTL activation, indicating that MTL
      activation reflects storage of associations, not merely their initial
      representation.

PMID- 22387597
TI  - Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A
      comparison with early and advanced Parkinson's disease.
AB  - Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common
      neuropathological marker, the presence of Lewy bodies in brain stem and basal
      forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the
      neocortex, and, in it's more common form, with Alzheimer-type pathological
      markers, particularly amyloid plaques. Published neuropsychological studies have
      focused on the differential profiles of DLB and Alzheimer's disease (AD).
      However, it is presently unclear whether DLB should be classified as a variant of
      AD or PD. In the present study we compare a healthy age-matched control group
      with three groups of patients, one with DLB, and two with PD. One of the PD
      groups was early in the course (PD-E) and the second, more advanced group (PD-A),
      was matched on severity of cognitive impairment with the DLB group. The results
      show that DLB was associated with a different pattern of neuropsychological
      impairment than the PD-A group, particularly in tests believed to be mediated by
      prefrontal cortical regions.

PMID- 22387600
TI  - Anterior cruciate ligament strain and tensile forces for weight-bearing and non
      weight-bearing exercises: a guide to exercise selection.
AB  - There is a growing body of evidence documenting loads applied to the anterior
      cruciate ligament (ACL) for weight-bearing and non-weight-bearing exercises. ACL
      loading has been quantified by inverse dynamics techniques that measure anterior
      shear force at the tibiofemoral joint (net force primarily restrained by the
      ACL), ACL strain (defined as change in ACL length with respect to original length
      and expressed as a percentage) measured directly in vivo, and ACL tensile force
      estimated through mathematical modeling and computer optimization techniques. A
      review of the biomechanical literature indicates the following: ACL loading is
      generally greater with non-weight-bearing compared to weight-bearing exercises;
      with both types of exercises, the ACL is loaded to a greater extent between 10
      degrees  to 50 degrees  of knee flexion (generally peaking between 10 degrees 
      and 30 degrees ) compared to 50 degrees  to 100 degrees  of knee flexion; and
      loads on the ACL change according to exercise technique (such as trunk position).
      Squatting with excessive forward movement of the knees beyond the toes and with
      the heels off the ground tends to increase ACL loading. Squatting and lunging
      with a forward trunk tilt tend to decrease ACL loading, likely due to increased
      hamstrings activity. During seated knee extension, ACL force decreases when the
      resistance pad is positioned more proximal on the anterior aspect of the lower
      leg, away from the ankle. The evidence reviewed as part of this manuscript
      provides objective data by which to rank exercises based on loading applied to
      the ACL. The biggest challenge in exercise selection post-ACL reconstruction is
      the limited knowledge of the optimal amount of stress that should be applied to
      the ACL graft as it goes through its initial incorporation and eventual
      maturation process. Clinicians may utilize this review as a guide to exercise
      selection and rehabilitation progression for patients post-ACL reconstruction.

PMID- 22387599
TI  - Analysis of serum genome-wide microRNAs for breast cancer detection.
AB  - OBJECTIVE: Among methods for profiling levels of miRNAs, next-generation
      sequencing (NGS) has an effective one for genome-wide profiles, which not only
      can accurately quantify known miRNAs expression, but also discovery novel miRNAs.
      In this paper, we investigated that whether specific miRNAs were co-expressed in
      the serum and tissue of breast cancer (BC) patients as novel biomarkers by SOLiD
      sequencing. METHODS: Different miRNA expression profiles of serum and tissue in
      breast cancer patients and control subjects were obtained by NGS -SOLiD
      sequencing. Real-time PCR was used to selected and validated candidate miRNA
      biomarkers. Novel miRNAs were predicted by computational pipeline, and validated
      by Northern blot analysis. RESULTS: Of genome-wide miRNA analysis using SOLiD
      sequencing, 7 miRNAs were found to be co-upregulated (i.e., miR-103, miR-23a, miR
      29a, miR-222, miR-23b, miR-24 and miR-25). miR-222 was significantly increased in
      the serum of BC patients by further validation(P<0.05), which may be a useful
      biomarker for differentiating BC patients from controls with receiver operating
      characteristic (ROC) curve area 0.67 of (95% CI=0.5649 to 0.7775). A novel miRNA,
      named miR-BS1 was preliminarily identified and validated. Pre-miR-BS1 has a
      characteristic secondary structure. Mature miR-BS1 expression was detected in MCF
      7 and MDA-MB-231 cells. Through gene ontology analysis, predicted target genes of
      miR-BS1, such as FOXO3 and KRAS, were involved in cancer-related signaling
      pathway. CONCLUSIONS: This study presented a connection between serum- and tissue
      based miRNA of breast cancer which suggested that serum-miRNAs may be potential
      biomarkers for BC detection. And next-generation sequencing will provide a robust
      platform for miRNA profilings.

PMID- 22387601
TI  - Ameliorative effect Trichosanthes dioica root against experimentally induced
      arsenic toxicity in male albino rats.
AB  - The present study evaluated the ameliorative potential of hydroalcoholic extract
      of Trichosanthes dioica root (TDA) against arsenic induced toxicity in male
      albino rats. TDA (5 and 10mg/kg) was administered orally to rats for 20
      consecutive days before oral administration of sodium arsenite (10mg/kg) for 8
      days. Then the body weights, organ weights, haematological profiles, serum
      biochemical profile; hepatic and renal antioxidative parameters viz. lipid
      peroxidation, reduced and oxidized glutathione, glutathione-S-transferase,
      glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and
      DNA fragmentation were evaluated. Pretreatment with TDA markedly and
      significantly normalized body weights, organ weights, haematological profiles,
      serum biochemical profile and significantly modulated all the hepatic and renal
      biochemical parameters and reduced DNA fragmentation in arsenic intoxicated rats.
      The present findings conclude that T. dioica root possessed remarkable
      ameliorative effect against arsenic induced organ toxicity in male albino rats
      mediated by alleviation of arsenic induced oxidative stress by multiple
      mechanisms.

PMID- 22387602
TI  - Oxidative and apoptotic effects of lambda-cyhalothrin modulated by piperonyl
      butoxide in the liver of Oreochromis niloticus.
AB  - The aim of this study was to investigate the toxic effects of pyrethroid
      pesticide lambda-cyhalothrin in the presence of piperonyl butoxide as a modulator
      in the liver of juvenile Oreochromis niloticus. LC(50) (96h) value of lambda
      cyhalothrin was determined as 2.901MUg/L for O. niloticus. The fish were exposed
      to 0.48MUg/L (1/6 of the 96-h LC(50)) lambda-cyhalothrin and 10MUg/L piperonyl
      butoxide for 96-h and 15-d. tGSH, GSH, GSSG, Hsp70 and TBARS contents, GPx, GR,
      GST and caspase-3 enzymes activities were determined. Lambda-cyhalothrin caused
      increases in tGSH, GSH, TBARS contents, and GST activity. Piperonyl butoxide
      treatment with lambda-cyhalothrin caused significant increases in tGSH GSH,
      Hsp70, TBARS contents, and GPx and GST activities while caspase-3 activity was
      decreased. The results of the present study revealed that lambda-cyhalothrin
      caused oxidative stress which upregulated GSH and GSH-related enzymes. Piperonyl
      butoxide increased the oxidative stress potential and apoptotic effects of lambda
      cyhalothrin.

PMID- 22387603
TI  - Protective effect of Hypericum perforatum L. on serum and hair trace elements in
      rats 7,12-dimethylbenz[a]anthracene-induced oxidative stress.
AB  - The study was designed to assess the effect of Hypericum perforatum L. (H.P) on
      serum and hair trace elements and mineral levels, oral administration of 7,12
      dimethylbenz[a]anthracene (DMBA) induced oxidative stress in Sprague-Dawley
      female rats. Analysis of the trace element has been carried out using atomic
      absorption spectrophotometer method at end of 60th day. It has been found out
      that the DMBA group contained statistically lower Zn and Cr compared to the
      control group (p<0.01) and (p<0.05), Cu, Mg and Na contained higher than control
      group (p<0.05), (p<0.05) and (p<0.05). In DMBA+H.P group, Zn higher and Na lower
      than DMBA group (p<0.05), (p<0.05), in hair samples Cd, K and Zn contained lower
      DMBA compared to the control group (p<0.05), (p<0.05) and (p<0.05). In group
      DMBA+H.P, Cd was higher than DMBA group and Cr lowered accordance with control
      group (p<0.05). The present study demonstrated significantly positive and
      beneficial effect of H.P on the concentration levels of Zn and Na in serum, also
      on Cd levels in hair between DMBA and DMBA+H.P groups.

PMID- 22387604
TI  - Transcriptome analysis of rosette and folding leaves in Chinese cabbage using
      high-throughput RNA sequencing.
AB  - In this study, we report the first use of RNA-sequencing to gain insight into the
      wide range of transcriptional events that are associated with leafy head
      development in Chinese cabbage. We generated 53.5 million sequence reads (90 bp
      in length) from the rosette and heading leaves. The sequence reads were aligned
      to the recently sequenced Chiifu genome and were analyzed to measure the gene
      expression levels, to detect alternative splicing events and novel transcripts,
      to determine the expression of single nucleotide polymorphisms, and to refine the
      annotated gene structures. The analysis of the global gene expression pattern
      suggests two important concepts, which govern leafy head formation. Firstly, some
      stimuli, such as carbohydrate levels, light intensity and endogenous hormones
      might play a critical role in regulating the leafy head formation. Secondly, the
      regulation of transcription factors, protein kinases and calcium may also be
      involved in this developmental process.

PMID- 22387605
TI  - Visemic processing in audiovisual discrimination of natural speech: a
      simultaneous fMRI-EEG study.
AB  - In a noisy environment, visual perception of articulatory movements improves
      natural speech intelligibility. Parallel to phonemic processing based on auditory
      signal, visemic processing constitutes a counterpart based on "visemes", the
      distinctive visual units of speech. Aiming at investigating the neural substrates
      of visemic processing in a disturbed environment, we carried out a simultaneous
      fMRI-EEG experiment based on discriminating syllabic minimal pairs involving
      three phonological contrasts, each bearing on a single phonetic feature
      characterised by different degrees of visual distinctiveness. The contrasts
      involved either labialisation of the vowels, or place of articulation or voicing
      of the consonants. Audiovisual consonant-vowel syllable pairs were presented
      either with a static facial configuration or with a dynamic display of
      articulatory movements related to speech production. In the sound-disturbed MRI
      environment, the significant improvement of syllabic discrimination achieved in
      the dynamic audiovisual modality, compared to the static audiovisual modality was
      associated with activation of the occipito-temporal cortex (MT+V5) bilaterally,
      and of the left premotor cortex. While the former was activated in response to
      facial movements independently of their relation to speech, the latter was
      specifically activated by phonological discrimination. During fMRI, significant
      evoked potential responses to syllabic discrimination were recorded around 150
      and 250 ms following the onset of the second stimulus of the pairs, whose
      amplitude was greater in the dynamic compared to the static audiovisual modality.
      Our results provide arguments for the involvement of the speech motor cortex in
      phonological discrimination, and suggest a multimodal representation of speech
      units.

PMID- 22387606
TI  - Differences in word recognition between early bilinguals and monolinguals:
      behavioral and ERP evidence.
AB  - We investigated the behavioral and brain responses (ERPs) of bilingual word
      recognition to three fundamental psycholinguistic factors, frequency, morphology,
      and lexicality, in early bilinguals vs. monolinguals. Earlier behavioral studies
      have reported larger frequency effects in bilinguals' nondominant vs. dominant
      language and in some studies also when compared to corresponding monolinguals. In
      ERPs, language processing differences between bilinguals vs. monolinguals have
      typically been found in the N400 component. In the present study, highly
      proficient Finnish-Swedish bilinguals who had acquired both languages during
      childhood were compared to Finnish monolinguals during a visual lexical decision
      task and simultaneous ERP recordings. Behaviorally, we found that the response
      latencies were overall longer in bilinguals than monolinguals, and that the
      effects for all three factors, frequency, morphology, and lexicality were also
      larger in bilinguals even though they had acquired both languages early and were
      highly proficient in them. In line with this, the N400 effects induced by
      frequency, morphology, and lexicality were larger for bilinguals than
      monolinguals. Furthermore, the ERP results also suggest that while most inflected
      Finnish words are decomposed into stem and suffix, only monolinguals have
      encountered high frequency inflected word forms often enough to develop full-form
      representations for them. Larger behavioral and neural effects in bilinguals in
      these factors likely reflect lower amount of exposure to words compared to
      monolinguals, as the language input of bilinguals is divided between two
      languages.

PMID- 22387607
TI  - Event-related potentials elicited in mothers by their own and unfamiliar infants'
      faces with crying and smiling expression.
AB  - Crying by an infant signals an urgent desire for care and protection. Because of
      the special relationship between a mother and her infant and the signal value of
      her crying, it is plausible to suggest that the maternal brain efficiently
      processes crying by infants. In the present study, we examined this hypothesis by
      measuring event-related potentials in mothers while they observed crying or
      smiling by their own or unfamiliar infants embedded within a train of neutral
      expressions. We found that the amplitude of the face-specific N170 component was
      enlarged for crying regardless of familiarity. The P300 component, which reflects
      a later cognitive evaluation stage of stimulus processing, was decomposed into
      functionally distinct components by temporal principal component analysis. The
      amplitude of the third temporal factor, which corresponds to the earliest portion
      of the P300, was larger when a mother observed her own infant crying than for the
      other conditions. Moreover, onset latency of P300 was shortest when mothers
      observed their own infant crying. These results indicate that mothers process
      their own infant's crying more efficiently than smiling by their own infant or
      crying by an unfamiliar infant.

PMID- 22387608
TI  - Hemispheric asymmetries of functional connectivity and grey matter volume in the
      default mode network.
AB  - Resting state networks such as the default mode network have been widely
      reported. Although a plethora of information on its functional relevance has been
      generated, little is known about lateralization or hemisphere asymmetry within
      the DMN. We used high-resolution resting state fMRI and T1 3D data to investigate
      such asymmetries in two groups of healthy subjects, one right-handed and one left
      handed. Independent component analysis and the dual regression approach were
      carried out to identify functional asymmetries, while voxel-based morphometry was
      used to identify structural asymmetries in grey matter volume within the DMN.
      Greater leftward functional connectivity was observed in the posterior cingulate
      gyrus (PCG) for both groups. Leftward functional asymmetry was observed in the
      thalamus and rightward functional asymmetries were observed in the middle frontal
      and middle/superior temporal gyrus in the right-handed group. Rightward
      asymmetries in grey matter volume were observed in the posterior portion of the
      PCG for both groups. The right-handed group exhibited leftward structural
      asymmetries in the anterior portion of the PCG and in the middle frontal and
      posterior portion of the middle temporal gyrus, while rightward asymmetries were
      observed in the posterior portion of the PCG and anterior portions of temporal
      regions. These results suggest that functional connectivity and grey matter
      volume are not equally distributed between hemispheres within the DMN, and that
      functional asymmetries are not always reflected or determined by structural
      asymmetries.

PMID- 22387609
TI  - A novel method for the rapid determination of beta-amyloid toxicity on acute
      hippocampal slices using MTT and LDH assays.
AB  - It is difficult task to measure precisely the toxic effect of beta-amyloid (Abeta
      1-42) peptides and also the protective effect of novel drug candidates against
      Abeta-peptides. The widely used MTT-assay in cell lines or primary cell cultures
      could be insensitive against Abeta-peptides. We describe here an easy and
      relevant method for testing Abeta 1-42 toxicity on acute hippocampal slices
      derived from rat. Brain slice viability in different conditions was measured
      using MTT and LDH assays. The concomitant use of these two assays can give
      detailed and relevant results on the toxic effect of Abeta 1-42 in oxygen-glucose
      deprived (OGD) acute brain slice model. Both assays are capable of quantifying
      tissue viability by measuring optical density (OD). We found that simultaneous
      application of OGD and Abeta 1-42 treatment induced a more intensive decrease in
      hippocampal slice viability than their separate effects. The use of MTT and LDH
      assay for quantifying brain slice viability proved to be an easy ex vivo method
      for investigating Abeta toxicity. Testing brain slices is more relevant in
      Alzheimer's Disease research than using in vitro cell cultures, due to
      maintenance of the three dimensional cellular network, the cell variability and
      intact cell connections.

PMID- 22387616
TI  - Glycosphingolipid synthesis is essential for MDCK cell differentiation.
AB  - Glycosphingolipids (GSLs), which are highly concentrated at the apical membrane
      of polarized epithelial cells, are key components of cell membranes and are
      involved in a large number of processes. Here, we investigated the ability of
      hypertonicity (high salt medium) to induce Madin-Darby Canine Kidney (MDCK) cell
      differentiation and found an increase in GSL synthesis under hypertonic
      conditions. Then, we investigated the role of GSLs in MDCK cell differentiation
      induced by hypertonicity by using two approaches. First, cultured cells were
      depleted of GSLs by exposure to D-threo-1-phenyl-2-decanoylamino-3-morpholino-1
      propanol (D-PDMP). Second, cells were transfected with an siRNA specific to
      glucosylceramide synthase, the key enzyme in GSL synthesis. Exposure of cells to
      both treatments resulted in the impairment of the development of the apical
      membrane domain and the formation of the primary cilium. Enzymatic inhibitions of
      the de novo and the salvage pathway of GSL synthesis were used to determine the
      source of ceramide responsible of the GSL increase involved in the development of
      the apical membrane domain induced by hypertonicity. The results from this study
      show that extracellular hypertonicity induces the development of a differentiated
      apical membrane in MDCK cells by performing a sphingolipid metabolic program that
      includes the formation of a specific pool of GSLs. The results suggest as
      precursor a specific pool of ceramides formed by activation of a Fumonisin B1
      resistant ceramide synthase as a component of the salvage pathway.

PMID- 22387617
TI  - Metabolomics reveals the metabolic map of procainamide in humans and mice.
AB  - Procainamide, a type I antiarrhythmic agent, is used to treat a variety of atrial
      and ventricular dysrhythmias. It was reported that long-term therapy with
      procainamide may cause lupus erythematosus in 25-30% of patients. Interestingly,
      procainamide does not induce lupus erythematosus in mouse models. To explore the
      differences in this side-effect of procainamide between humans and mouse models,
      metabolomic analysis using ultra-performance liquid chromatography coupled with
      electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI
      QTOFMS) was conducted on urine samples from procainamide-treated humans, CYP2D6
      humanized mice, and wild-type mice. Thirteen urinary procainamide metabolites,
      including nine novel metabolites, derived from P450-dependent, FMO-dependent
      oxidations and acylation reactions, were identified and structurally elucidated.
      In vivo metabolism of procainamide in CYP2D6-humanized mice as well as in vitro
      incubations with microsomes and recombinant P450s suggested that human CYP2D6
      plays a major role in procainamide metabolism. Significant differences in N
      acylation and N-oxidation of the drug between humans and mice largely account for
      the interspecies differences in procainamide metabolism. Significant levels of
      the novel N-oxide metabolites produced by FMO1 and FMO3 in humans might be
      associated with the development of procainamide-induced systemic lupus
      erythematosus. Observations based on this metabolomic study offer clues to
      understanding procainamide-induced lupus in humans and the effect of P450s and
      FMOs on procainamide N-oxidation.

PMID- 22387618
TI  - Cannabinoid receptor trafficking in peripheral cells is dynamically regulated by
      a binary biochemical switch.
AB  - The cannabinoid G protein-coupled receptors (GPCRs) CB1 and CB2 are expressed in
      different peripheral cells. Localization of GPCRs in the cell membrane determines
      signaling via G protein pathways. Here we show that unlike in transfected cells,
      CB receptors in cell lines and primary human cells are not internalized upon
      agonist interaction, but move between cytoplasm and cell membranes by ligand
      independent trafficking mechanisms. Even though CB receptors are expressed in
      many cells of peripheral origin they are not always localized in the cell
      membrane and in most cancer cell lines the ratios between CB1 and CB2 receptor
      gene and surface expression vary significantly. In contrast, CB receptor cell
      surface expression in HL60 cells is subject to significant oscillations and CB2
      receptors form oligomers and heterodimers with CB1 receptors, showing
      synchronized surface expression, localization and trafficking. We show that
      hydrogen peroxide and other nonspecific protein tyrosine phosphatase inhibitors
      (TPIs) such as phenylarsine oxide trigger both CB2 receptor internalization and
      externalization, depending on receptor localization. Phorbol ester-mediated
      internalization of CB receptors can be inhibited via this switch. In primary
      human immune cells hydrogen peroxide and other TPIs lead to a robust
      internalization of CB receptors in monocytes and an externalization in T cells.
      This study describes, for the first time, the dynamic nature of CB receptor
      trafficking in the context of a biochemical switch, which may have implications
      for studies on the cell-type specific effects of cannabinoids and our
      understanding of the regulation of CB receptor cell surface expression.

PMID- 22387619
TI  - Hydrogen sulfide stimulates the catalytic activity of a heme-regulated
      phosphodiesterase from Escherichia coli (Ec DOS).
AB  - Ec DOS, a heme-regulated phosphodiesterase from Escherichia coli, is an oxygen
      sensor enzyme composed of a heme-bound O(2) sensor domain at the N-terminus and a
      catalytic domain at the C-terminus. The catalytic activity of Ec DOS is
      substantially enhanced with the formation of a Fe(II) heme-O(2) complex. The
      physiological importance of H(2)S as a fourth signaling gas molecule in addition
      to O(2), CO and NO is an emerging focus of research, since H(2)S participates in
      various physiological functions. In the present study, we showed that catalysis
      by Ec DOS is markedly increased by H(2)S under aerobic conditions. Absorption
      spectral findings suggest that SH(-)-modified heme iron complexes, such as
      Fe(III)-SH(-) and Fe(II)-O(2) complexes, represent the active species for H(2)S
      induced catalysis. We further examined the role of Cys residues in H(2)S-induced
      catalysis using Cys->Ala mutant enzymes. Based on the collective data, we
      speculate that H(2)S-induced catalytic enhancement is facilitated by an admixture
      of Fe(III)-SH(-) and Fe(II)-O(2) complexes formed during catalysis and
      modification of specific Cys residue(s) in the catalytic domain.

PMID- 22387620
TI  - Neural bases of falsification in conditional proposition testing: evidence from
      an fMRI study.
AB  - The ability of testing the validity of a conditional statement is important in
      our everyday life. However, the brain mechanisms underlying this process,
      especially falsification process which is important in daily life, but especially
      crucial to scientific reasoning and research is not as yet completely clear.
      Therefore, in the present study, we used event-related functional magnetic
      resonance imaging (fMRI) to examine the neural bases of the falsification process
      in testing the validity of a conditional statement as used in Wason's (1966)
      selection task. Our fMRI results showed that: (1) compared with the baseline
      condition, both Falsification (by using Modus Ponens, and Modus Tollens) and Non
      Falsification conditions (affirming the consequent, and denying the antecedent)
      activated the left frontal areas (BA44/45, or BA6), and basal ganglia, the areas
      previously found in the rule-guided conditional reasoning operations; the
      parietal area (BA40, BA7) for recruiting cognitive resources to represent and
      maintain the different evidential information in working memory. (2) The left
      middle frontal gyrus (BA9) and cerebellum were shown to be activated in the
      contrast of Falsification condition versus Non-Falsification condition and in the
      contrast of MT versus Non-Falsification condition. These results indicated that
      the left middle frontal gyrus (BA9) might be the key brain region involved in the
      falsification process of conditional statement for which abstracting and
      integrating logical relationships, and inhibiting the distraction of the
      irrelevant information were the essential processes. Moreover, the cerebellum was
      found to be responsible for constructing an internal working model. In addition,
      our brain imaging results might support the dual-process theory of reasoning.

PMID- 22387621
TI  - Polycystic ovary syndrome: Implications of measurement of plasma aldosterone,
      renin activity and progesterone.
AB  - A positive correlation between aldosterone, inflammatory parameters, blood
      pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been
      reported in the early estrogenic phase. The aim of the study was to measure
      plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day
      of the cycle, in women with PCOS and to consider the interrelationships between
      these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24
      years, range 21-28 years) and 53 age- and body mass index-matched healthy
      controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and
      Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in
      PCOS women than controls. Positive correlations were found in PCOS but not in
      controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA,
      (iii) PRA and progesterone. Mean blood pressures were within the normal range but
      significantly higher in PCOS than controls. The increase of plasma aldosterone,
      ARR and blood pressure in PCOS compared with controls is consistent with an
      increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with
      spironolactone could counteract both the hyperandrogenism and reduce future
      cardiovascular risk.

PMID- 22387624
TI  - Surgical access on the superior ophthalmic vein to the cavernous sinus dural
      fistula for embolization.
AB  - BACKGROUND: Direct surgical exposure and cannulation (DSEC) of the superior
      ophthalmic vein (SOV) can be used as an alternative approach for the endovascular
      treatment of cavernous sinus dural fistulas (CSDF) that fail conventional
      endovascular access. The aim of this study was to report the techniques,
      effectiveness and safety of DSEC of the SOV in these cases. METHODS: Between June
      2007 and June 2011, nine CSDF in nine patients who presented with ocular signs
      and symptoms were embolized using DSEC of the SOV when the CSDF could not be
      treated via the transarterial or transfemoral venous route. RESULTS: All nine
      patients were successfully treated by introduction of Onyx in conjunction with
      detachable coils through the catheterized SOV to the affected cavernous sinus. No
      exposure or catheterization of the SOV proved difficult. Symptoms and signs
      resolved completely in all patients after successful occlusion of the CSDF. There
      were no intraoperative complications. All patients underwent follow-up cerebral
      angiography at least 3 months after treatment, and none showed recurrence of the
      fistula. CONCLUSION: DSEC of the SOV for embolization of a CSDF is a good
      alternative treatment when conventional venous routes are inaccessible. Surgical
      access to the SOV is direct and can be performed safely. The use of Onyx in
      conjunction with detachable coils is safe and effective for symptomatic CSDF.

PMID- 22387625
TI  - One-step synthesis of stoichiometric Cu2ZnSnSe4 as counter electrode for dye
      sensitized solar cells.
AB  - Cu(2)ZnSnSe(4) (CZTSe) nanoparticles with diameters of 200-300 nm were
      synthesized by one-step solvothermal method without surfactants or templates. The
      structure, composition and morphology of CZTSe nanoparticles were characterized
      by XRD, XPS, Raman spectrum, EDS, FESEM and TEM. The results indicated that the
      nanoparticles were single phase and nearly stoichiometric composition. CZTSe
      nanoparticles drop-casted onto FTO substrate were used as counter electrode (CE)
      in dye-sensitized solar cells (DSSCs) for the first time, which exhibited Pt-like
      electrocatalytic activity for the reduction of I(3)(-) to I(-) in DSSCs. The J-V
      results demonstrated that the thickness of the film affected the photocurrent
      density and fill factor remarkably, which resulted from the difference of
      electrocatalytic sites and resistance with different thickness films. And a best
      efficiency of 3.85% was obtained by adjusting the film thickness. The work
      presents a new approach for developing low-cost, facile fabrication CZTSe
      nanoparticles, and demonstrates CZTSe can be explored as a low-cost alternative
      for expensive and scare Pt in DSSCs.

PMID- 22387626
TI  - Cerebrospinal fluid Abeta40 and Abeta42: Natural course and clinical usefulness.
AB  - Amyloid beta protein 40 (Abeta40) and 42 (Abeta42), major components of senile
      plaque amyloids, are physiological peptides present in the brain, cerebrospinal
      fluid (CSF) and plasma. The levels of CSF Abeta40 and Abeta42(43) show a U-shaped
      natural course in normal aging. The increase of Abeta42(43) over 60 years of age
      is inhibited in Alzheimer's disease (AD). This specific alteration of CSF
      Abeta42(43) correlates with Abeta deposits in the AD brain providing a biological
      basis for a biomarker of AD. In the GTT2 study, assays of the CSF Abeta ratio
      [(Abeta40/ Abeta42(43)] showed a diagnostic sensitivity (59%) specificity (88%)
      The levels of the Abeta ratio increased from early to late stages of AD.
      Combination assays of CSF tau and Abeta ratio provided further efficient
      diagnostic sensitivity (81%) reliability of the assay may prompt worldwide usage
      of these CSF biomarkers for Alzheimer's patients.

PMID- 22387627
TI  - Foot-and-mouth disease virus causes a decrease in spleen dendritic cells and the
      early release of IFN-alpha in the plasma of mice. Differences between infectious
      and inactivated virus.
AB  - Foot-and-mouth disease (FMD) is a highly contagious and acute viral disease of
      cloven-hoofed animals. From an economical point of view, it is the most important
      disease of livestock worldwide. It is known that the virus interacts with
      dendritic cells, both in the natural host and in mice, but the impact of this
      interaction on the adaptive immune response is controversial. Currently available
      vaccines are based on inactivated forms of the FMD virus. Little is known about
      the differences between infectious and inactivated virus, in terms of dendritic
      cell subsets involved in immune response activation. The present work, which was
      carried out in the murine model, shows that live virus infection induces a
      reduction in splenic dendritic cell subsets. In addition, lymphocyte
      proliferation is inhibited in the early stages of infection associated with IFN
      alpha induction, but is restored to normal values 5 days post-infection when pro
      inflammatory cytokines was produced. In contrast, the inactivated virus increases
      the percentage of plasmacytoid dendritic cells in the spleen and the production
      of IL-10, which triggers the activation of a T regulatory response.

PMID- 22387628
TI  - Developing an implicit measure of disgust propensity and disgust sensitivity:
      examining the role of implicit disgust propensity and sensitivity in obsessive
      compulsive tendencies.
AB  - BACKGROUND AND OBJECTIVES: There is increasing evidence that disgust responding
      occurs at both a primary and secondary level in the form of disgust propensity
      and disgust sensitivity. The unique contributions of anxiety and disgust need to
      be established if disgust is to be implicated in the etiology of anxiety
      disorders such as obsessive-compulsive disorder (OCD). The primary objective of
      the current study was to develop two separate implicit measures of disgust
      propensity and sensitivity and to explicate the role of implicit disgust
      propensity and sensitivity in avoidance behavior and OC tendencies. METHODS: The
      current study (N = 33 undergraduate students) utilized a measure of implicit
      cognition, the Implicit Relational Assessment Procedure (IRAP), to independently
      analyze disgust propensity and disgust sensitivity. In addition, a series of
      behavioral approach tasks (BAT) and questionnaires measuring general disgust,
      obsessive-compulsive (OC) tendencies and general psychopathology were implemented
      to validate the implicit measures. RESULTS: Disgust sensitivity predicted
      avoidance behavior on the BATs independent of disgust propensity and anxiety,
      while disgust propensity did not. Both disgust propensity and sensitivity
      predicted self-reported OC tendencies and individually predicted obsessing and
      washing concerns, respectively. LIMITATIONS: Our findings are based on a non
      clinical student sample and further research is required for generalization to
      OCD. CONCLUSIONS: The implicit measures appeared to be measuring two separate
      constructs and had differential relationships with behavior and OC tendencies.
      Overall, the results support current theories relating to pathological disgust
      and OCD.

PMID- 22387629
TI  - Protection of pigs against genital Chlamydia trachomatis challenge by parenteral
      or mucosal DNA immunization.
AB  - The current study evaluates combined aerosol-vaginal delivery of a MOMP-based
      Chlamydia trachomatis (serovar E) DNA vaccine in a pig genital challenge model.
      Most non-replicating antigens are rather poor mucosal immunogens in comparison to
      replicating antigens. Therefore, a mucosal administered DNA vaccine, which
      actually mimics a live vaccine, could be promising. Protection was promoted by
      plasmids encoding the porcine granulocyte macrophage-colony stimulating factor
      (pcDNA3.1zeo::GM-CSF), the Escherichia coli thermo-labile enterotoxin (LT)
      subunit A (plasmid PJV2004::LTa) and subunit B (plasmid PJV2005::LTb). Mucosal C.
      trachomatis DNA vaccination induced significant protection against genital C.
      trachomatis challenge although the infection could not be eradicated. Intradermal
      immunization was significantly less efficient in protecting experimentally
      infected pigs. Protection was correlated with efficient T cell priming and
      significantly higher serum IgA titers following primo vaccination.

PMID- 22387630
TI  - Preclinical evidence for implementing a prime-boost vaccine strategy for
      tuberculosis.
AB  - In this review, published peer-reviewed preclinical studies using prime-boost
      tuberculosis (TB) vaccine regimens in animal challenge models for tuberculosis
      have been evaluated. These studies have been divided into groups that describe
      prime-boost vaccine combinations that performed better than, equivalent to, or
      worse than the currently used BCG vaccine. Review of the data has revealed
      interesting findings, including that more than half of the published studies
      using BCG as a prime combined with a novel boost vaccine give better efficacy
      than BCG alone and that the greatest reduction in Mycobacterium tuberculosis
      (M.tb.) colonization of animal tissues is provided by viral vectored vaccines
      delivered intranasally. Careful evaluation of these data should assist in
      defining the value of prime-boost regimens for advancement into human TB vaccine
      trials and stimulate the development of criteria for choosing which vaccine
      candidates should be studied further.

PMID- 22387632
TI  - Pathogenesis of lupus-like nephritis through autoimmune antibody produced by
      CD180-negative B lymphocytes in NZBWF1 mouse.
AB  - Toll-like receptors appear to play an important role in the pathogenesis of lupus
      like nephritis in mice. In human and mouse, CD180 is a homologue of TLR4. In SLE
      patients, the number of CD180-negative B cells in peripheral blood changes in
      parallel with disease activity. In the present study using NZBWF1 mice, the
      population of splenic CD180-negative B cells increased with progression of renal
      lesions and aging. These cells produced both anti-dsDNA and histone antibodies;
      the peripheral blood levels of anti-dsDNA antibody increased markedly with aging.
      B cells infiltrating into renal lesions were CD180-negative and produced anti
      dsDNA antibody. Considered together, these findings indicate that CD180-negative
      B cells contribute significantly to development of SLE-like morbidity in NZBWF1
      mice by autoantibody production.

PMID- 22387640
TI  - Gabapentin use in the prevention of succinylcholine-induced fasciculation and
      myalgia.

PMID- 22387641
TI  - Is methicillin-resistant Staphylococcus aureus involved in community acquired
      skin and soft tissue infections? Experience from a tertiary care centre in
      Mumbai.
AB  - BACKGROUND: To improve the empiric antimicrobial therapy of community-acquired
      (CA) skin and soft tissue infections (SSTIs), it is necessary to generate data on
      the current spectrum and susceptibility profile of associated bacteria. CA
      methicillin-resistant Staphylococcus aureus (CA MRSA) is increasingly being
      reported in SSTIs in India and globally. AIMS: The present study was undertaken
      to determine the bacterial profile of CA-SSTIs, to know the contribution of MRSA
      in these infections, to determine inducible clindamycin resistance in S. aureus
      and to compare the resistance patterns of isolates from hospital-acquired (HA)
      SSTIs. MATERIALS AND METHODS: Eight hundred and twenty patients with CA SSTIs
      were prospectively studied. Pus samples were cultured and antimicrobial
      susceptibility pattern determined. Inducible clindamycin resistance was detected
      by D-test. Laboratory records were analyzed retrospectively to generate data on
      HA SSTIs. RESULTS: 619 isolates were recovered in CA-SSTIs, of which S. aureus
      (73%) and Streptococci (12%) were the most common. Pseudomonas aeruginosa (28%)
      and Acinetobacter spp (18%) were the predominant HA-SSTI pathogens.
      Susceptibility of CA S. aureus to antibiotics tested was, penicillin (6%), co
      trimoxazole (20%), ciprofloxacin (37%), cefazolin (100%), erythromycin (84%),
      clindamycin (97%), gentamicin (94%) and fusidic acid (95%). No MRSA was found in
      CA SSTIs whereas 45% of HA S. aureus strains were methicillin-resistant. HA
      strains demonstrated significantly higher resistance as compared to their CA
      counterparts (P<0.001). D test was positive in 22% of CA S. aureus tested.
      CONCLUSIONS: In CA SSTIs, methicillin-susceptible S. aureus is the predominant
      pathogen. Penicillinase-resistant penicillins, clindamycin and erythromycin in
      that order can be used as suitable antimicrobials for empiric therapy. D test
      should be carried out routinely. No CA MRSA was detected in the present series.

PMID- 22387642
TI  - Effect of cardiopulmonary bypass on tissue injury markers and endothelial
      activation during coronary artery bypass graft surgery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is done either using
      cardiopulmonary bypass (CPB) or without using CPB (OPCAB). But, recently, reports
      have shown that CPB is associated with increased postoperative morbidity because
      of the involvement of many systems. AIMS: The aim of this prospective study was
      to evaluate the influence of the technique of surgery on various tissue injury
      markers and the extent of endothelial activation in patients undergoing CABG and
      OPCAB coronary revascularization. SETTINGS AND DESIGN: This study was conducted
      at a tertiary healthcare center during the period May 2008 to December 2009.
      MATERIALS AND METHODS: This was a prospective nonrandomized blinded study. The
      activities of Creatine Phosphokinase (CK) and its isoenzyme CK-MB, Lactate
      dehydrogenase (LDH), levels of cardiac Troponin I, soluble vascular cell adhesion
      molecule-1 (sVCAM-I) and systemic nitric oxide production were assessed.
      STATISTICAL ANALYSIS: All the results were expressed as Mean +/- SD. P value <=
      0.05 was considered significant. The statistical analysis was carried out using
      SPSS Version 11.5-computer software (SPSS Inc., Chicago, IL, USA). RESULTS: The
      surgical trauma had elevated CK, CK-MB and Troponin I in both the groups and
      further elevation was seen in the CABG group in comparison to OPCAB (P<0.001).
      The Troponin I concentrations showed an increase from 0.11 +/- 0.02
      preoperatively to 6.59 +/- 0.59 (ng/ml) at 24 h (P<0.001) compared to the OPCAB
      group. Mean serum levels of sVCAM-1 increased significantly after surgery in both
      the groups (P<0.02). To determine serum nitric oxide (NO) production, NO2- and
      NO3- (stable end products of NO oxidation) were analyzed which also increased
      significantly at 24 h in both the groups. But the increase was not significant at
      48 h in both the groups compared to the preoperative value in our study.
      CONCLUSION: The present study indicates that, despite comparable surgical trauma,
      the OPCAB significantly reduces tissue injury. The overall pattern of endothelial
      activation after OPCAB is significantly lower than that after CABG. This may
      contribute to improved organ function, and improved postoperative recovery.

PMID- 22387643
TI  - An epidemic outbreak of Vibrio Cholerae El Tor 01 serotype ogawa biotype in a
      Lalpur town, Jamnagar, India.
AB  - BACKGROUND: On December 19, 2010, 57 cases of gastroenteritis were reported in
      the community health center of Lalpur town. A rapid response team was sent to
      investigate the outbreak on December 21, 2010. AIM: To identify the source, to
      institute control and prevention measures. MATERIALS AND METHODS: The outbreak
      was confirmed using the previous Integrated Integrated Disease Surveillance
      Project (IDSP) data. Detailed history was taken, line listing of patients and
      house-to-house investigations were done. Environmental investigation and
      laboratory investigation of stool samples were also done. As the study was
      conducted during emergency response to the outbreak and was designed to provide
      information to orient the public health response, ethical approval was not
      required. Remedial measures were implemented. RESULTS: Three hundred and thirty
      cases were reported during December 19, 2010 to January 2, 2011 in Lalpur town of
      Jamnagar district. Nineteen patients were found to be positive for Vibrio
      Cholerae 01 serotype ogawa biotype out of 117 stool samples. The mean age of
      patients was 24.23 +/- 19.01 years. The outbreak had 1.88% attack rate with no
      mortality and 59.1% cases had to be admitted. Investigations revealed that the
      epidemic was waterborne. Ten leakages were found in the pipelines of the affected
      areas of Lalpur town near two riverbanks. CONCLUSION: Among identified gaps,
      delays in the initiation of the investigation of the epidemic and repairing of
      leakages were most important. In India, waterborne epidemics are usual
      occurrences during the year. In this scenario, the village health and sanitation
      committee and water board should follow guidelines, and monitoring of water
      sources, proper sewage disposal and sanitation measures should be undertaken.

PMID- 22387644
TI  - Prophylactic use of gabapentin for prevention of succinylcholine-induced
      fasciculation and myalgia: a randomized, double-blinded, placebo-controlled
      study.
AB  - BACKGROUND: Succinylcholine is used for rapid-sequence induction of anesthesia.
      Fasciculations and myalgia are adverse effects. The pretreatment modalities
      prevent or minimize its adverse effects. AIMS: The present study is designed to
      evaluate the efficacy of gabapentin on the incidence of fasciculation and
      succinylcholine-induced myalgia. SETTINGS AND DESIGN: The study was conducted at
      a tertiary care teaching hospital in a randomized, double-blinded, placebo
      controlled manner. MATERIALS AND METHODS: Patients of both genders undergoing
      laparoscopic cholecystectomy were randomly assigned to two groups. Patients in
      Group I (Gabapentin group) received 600 mg of gabapentin orally 2 h prior to
      surgery and patients in Group II (placebo group) received matching placebo.
      Anesthesia was induced with fentanyl 3 MUg/kg, thiopentone 3-5 mg/kg and
      succinylcholine 1.5 mg/kg. All patients were observed and graded for
      fasciculations by a blinded observer and patients were intubated. Anesthesia was
      maintained with oxygen in air, sevoflurane and intermittent vecuronium bromide.
      After completion of surgery, neuromuscular blockade was reversed. A blinded
      observer recorded myalgia grade at 24 h. Patients were provided patient
      controlled analgesia with fentanyl for postoperative pain relief. STATISTICAL
      ANALYSIS: Demographic data, fasciculation grade, fentanyl consumption, and
      myalgia grade were compared using student t test and test of proportions.
      RESULTS: The study included 76 American Society of Anesthesiologists' Grade I or
      II patients of either gender undergoing laparoscopic cholecystectomy. But only 70
      patients completed the study. Results demonstrated that the prophylactic use of
      gabapentin significantly decreases the incidence and the severity of myalgia
      (20/35 vs. 11/35) (P<0.05) and decreases fentanyl consumption significantly in
      the study group (620+164 MUg vs. 989+238 MUg) (P<0.05) without any effects on the
      incidence and severity of fasciculations. CONCLUSIONS: Prophylactic use of
      gabapentin 600 mg in laparoscopic cholecystectomy decreases the incidence and
      severity of myalgia and fentanyl consumption.

PMID- 22387645
TI  - 5HT3 antagonists for prophylaxis of postoperative nausea and vomiting in breast
      surgery: a meta-analysis.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) are distressing adverse
      events following breast cancer surgery with an incidence of up to 80%. 5HT 3
      antagonists are commonly employed as drugs of first choice for PONV although
      there is no clear evidence favoring one pharmacological approach over another.
      AIMS: The objective of this meta-analysis is to compare the efficacy of 5HT 3
      antagonists against all non-5HT 3 antagonism-based pharmacological approaches as
      a preemptive strategy for PONV in women undergoing breast surgery. DESIGN: Meta
      analysis of Randomized Controlled Trials. MATERIALS AND METHODS: Literature
      search was conducted through PUBMED, reference lists, and Cochrane Central
      Register of Controlled Trials till June 2010 to identify eligible studies. Trials
      comparing 5-HT 3 antagonists with placebo or active controls for prophylaxis
      against PONV in women undergoing breast surgery were included. Two reviewers
      extracted the data independently. Methodological quality of each trial was
      assessed using Jadad score. RESULTS: Nineteen trials were included. All trials
      were of good methodological quality (Jadad score >3). 5HT 3 antagonists were
      found superior to placebo [Odds ratio (OR)=0.18 (0.13-0.26)] or active controls
      [OR=0.65 (0.47-0.91)] in the prevention of PONV. 5HT 3 antagonists were also
      superior to placebo in preventing nausea alone [OR=0.51 (0.34-0.76)], vomiting
      [OR=0.31 (0.20-0.47)] and the use of rescue antiemetics [OR=0.18 (0.11-0.28)]. No
      significant difference was observed in the use of rescue antiemetics as compared
      to active controls [0.59 (0.19 to 1.86)]. CONCLUSION: 5HT 3 antagonists are
      superior to other pharmacological interventions for the prevention of PONV in
      patients undergoing breast surgery under general anesthesia.

PMID- 22387646
TI  - Aliskiren, the first direct renin inhibitor for treatment of hypertension: the
      path of its development.
AB  - Standard treatments available today for treating hypertension is diuretics, beta
      blockers, angiotensin converting enzyme inhibitors (ACEs), angiotensin receptor
      blockers (ARBs), calcium channel blockers, a-blockers, vasodilators, and
      centrally acting drugs. It is difficult to achieve the optimized renin
      angiotensin aldosterone system suppression with currently available
      antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate
      the compensatory feedback mechanism that increases renin release and increase
      plasma renin activity. The first orally active direct renin inhibitors (DRIs)
      were developed in 1980s, including enalkiren, remikiren, and zankiren. However,
      poor absorption from the gastrointestinal tract, less bioavailability (<2%),
      short half life, and low potency hindered the development of these compounds.
      Aliskiren is the first DRI for the treatment of hypertension. Aliskiren is
      designed through a combination of molecular modeling techniques and crystal
      structure elucidation. Aliskiren effectively reduces the blood pressure as a mono
      therapy as well in combination therapy.

PMID- 22387647
TI  - Emergence of viral hemorrhagic fevers: is recent outbreak of Crimean Congo
      Hemorrhagic Fever in India an indication?
AB  - The emerging and re-emerging diseases are posing a great health risk for the last
      few years. One such category of diseases is viral haemorrhagic fevers (VHFs),
      which have emerged in the new territories, worldwide. Crimean Congo Hemorrhagic
      Fever (CCHF) cases, for the first time in India, were reported from Gujarat, in
      January 2011. The emergence of diseases not reported earlier, pose great economic
      and social challenge, burden health system, and create panic reaction.
      Nonetheless, with recent experience in control of epidemic diseases, and advances
      in basic scientific knowledge; the public health community is better prepared for
      these unexpected events. This review provides information to physicians on CCHF
      for managing outbreak, and identifies public health measures to prevent emergence
      and re-emergence of VHFs (including CCHF) in future. The authors suggest that
      though, there are a few challenging and unanswered questions, the public health
      preparedness still remains the key to control emerging and re-emerging diseases.
      The countries where virus activities have been reported need to be prepared
      accordingly.

PMID- 22387648
TI  - Strategies to reduce medication errors in pediatric ambulatory settings.
AB  - Worldwide, a large number of children are prescribed drugs on an outpatient
      basis. Medication errors are fairly common in these settings. Though this matter
      has been well recognized as a cause of concern, limited data is available from
      ambulatory settings. Medication errors can be defined as errors that may occur at
      any step, starting from ordering a medication, to dispensing, administration of
      the drug and the subsequent monitoring. The outcomes of such errors are variable
      and may range between those that are clinically insignificant to a life
      threatening event. The reasons for these medication errors are multi-factorial.
      Children are unable to administer medications to themselves and also require a
      strict weight-based dosing regimen. The risk factors associated with medication
      errors include complex regimens with multiple medications. Overdosing and under
      dosing (10-fold calculation errors), an increased or a decreased frequency of
      dosing or an inappropriate duration of administration of the medication, are
      frequently detected errors. The lack of availability of proper formulations adds
      to the confusion. The low level of literacy among the caregivers can aggravate
      this problem. There is a lack of proper reporting and monitoring mechanisms in
      most ambulatory settings, hence these errors remain unrecognized and often go
      unreported. This article summarizes the current available literature on
      medication errors in ambulatory settings and the possible strategies that can be
      adopted to reduce the burden of these errors in order to improve child care and
      patient safety. Voluntary, anonymous reporting can be introduced in the
      healthcare institutions to determine the incidence of these errors.

PMID- 22387649
TI  - Mesenteric fat necrosis after recent surgery causing bowel obstruction: a case
      report and review of the literature.
AB  - Mesenteric fat necrosis causing bowel obstruction is a rare occurrence with only
      one case reported in humans. It is due to accidental or surgical trauma to the
      adipose tissue with extracellular liberation of fat or enzymatic lysis of fat due
      to the release of lipases resulting in fibrosis. Preoperative imaging may often
      be misleading and fail to identify fat necrosis as the cause of bowel
      obstruction. As surgical intervention is the only suitable treatment option in
      cases of failed conservative treatment, the diagnosis is made postoperatively.
      There is no published advice on the management of mesenteric fat necrosis. We
      recommend safe operating techniques to minimize the risk of developing fat
      necrosis and its potential harmful consequences.

PMID- 22387650
TI  - Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST
      syndrome.
AB  - Clinical involvement of the peripheral nervous system in the calcinosis cutis,
      raynaud's phenomenon, esophageal dismotility, sclerodactyly and telangiectasia
      (CREST) variant of systemic sclerosis occurs infrequently and is characterized by
      axonal degeneration due to necrotizing vasculitis. We report a female patient
      with a known history of CREST syndrome, which developed a slowly progressive,
      distal symmetric demyelinating sensorimotor polyneuropathy (PN), with tremor and
      ataxia as prominent features, compatible with anti-myelin associated glycoprotein
      (MAG) PN. The diagnosis of PN was established by the presence of monoclonal
      immunoglobulin M anti-MAG antibodies (Thin-Layer Chromatography, Western Blot and
      enzyme-linked immunoabsorbent assay). Given the evidence that in CREST activation
      of T-helper cells is observed and that anti-MAG antibodies, despite the fact that
      they are T-cell-independent, may be influenced by an increase in T-helper
      function, the coexistence of these two rare autoimmune disorders in the same
      patient may not be incidental but related to the underlying immunological
      mechanisms involved.

PMID- 22387651
TI  - Paralysis caused by a large carbohydrate meal.

PMID- 22387652
TI  - Falciparum malaria troubling neurosurgeons.

PMID- 22387653
TI  - Development of botanical principles for clinical use in cancer: where are we
      lacking?
AB  - Development of drugs from plant sources (botanicals) for the treatment of cancer
      has not been successful in India, despite a plethora of medicinal plants and an
      equal number of experiments demonstrating anti-cancer activity of plant
      principles in vitro. There are several pitfalls in our approach to botanical drug
      development. Foremost is the lack of industry-academia collaborations in this
      field. Research goals in Indian academic institutions are generally short-term
      and mostly aimed at fulfilling the minimum requirements of a doctoral/MD or
      MPharm thesis. Secondly, quality assurance of herbal formulations is difficult to
      achieve and good manufacturing practices are expensive to implement. This could
      introduce bias during the biological evaluation of botanicals. A systematic
      approach covering a wide range of investigations including but not limited to
      mechanistic studies, potential herb-drug interactions, pharmacokinetics and
      bioavailability could help in the optimization of herbal formulations in the
      preclinical stage of development before they can be considered for clinical
      trials. Government initiatives such as Ayurveda, Unani, Siddha and Homeopathic
      have encouraged research in these areas, but are insufficient to promote focused
      and aggressive evaluation of potential herbs. Particular emphasis should be given
      to clinical pharmacokinetics, drug interactions and clinical trials in specific
      cancers for the evaluation of dosage, safety, efficacy and concomitant use with
      chemotherapy. Only such policies can result in meaningful evaluation of
      botanicals for cancer therapy.

PMID- 22387654
TI  - National list of essential medicines of India: the way forward.
AB  - Essential medicines lists have been shown to improve the quality and cost
      effectiveness of health care delivery when combined with proper procurement
      policies and good prescribing practices. The Ministry of Health, Government of
      India revised the National List of Essential Medicines of India (NLEMI 2011) in
      June 2011, eight years after the last revision. The NLEMI 2011 contains 348
      medicines and was prepared over one and a half years by 87 experts. Though there
      are some positive aspects to the list such as the documentation of a detailed
      description of the revision process, inclusion of many experts from various
      fields in the review committee, well written description of the essential
      medicines concept and others, a critical review of the list reveals areas of
      major and minor concerns. Improper medicine selection like the inclusion of a
      nearly obsolete medicine such as ether, an anesthetic agent; non-inclusion of
      pediatric formulations; spelling errors; and errors in the strengths of
      formulations diminishes the significance of the NLEMI 2011. In its present form,
      the NLEMI 2011 did not align with the Indian Pharmacopoeia, and the National
      Health Programs as well as the National Formulary of India 2010. Formatting
      errors, non-inclusion of an index page, syntax and spelling errors may also
      undermine the usefulness of the NLEMI 2011 as a reference material. An urgent
      revision of the NLEMI 2011 is suggested so as to avert misinforming the wider
      international and local readers.

PMID- 22387655
TI  - Contributions of ancient Indian physicians--implications for modern times.
AB  - Ayurveda traces its origins to contributions of mythological and real physicians
      that lived millennia earlier. In many respects, Western medicine also had similar
      origins and beliefs, however, the introduction of anatomical dissection and
      progressive application of scientific evidence based practices have resulted in
      divergent paths taken by these systems. We examined the lives, careers, and
      contributions made by nine ancient Indian physicians. Ancient texts, translations
      of these texts, books, and biographical works were consulted to obtain relevant
      information, both for Indian traditional medicine as well as for Western
      medicine. Ayurveda has retained principles enunciated by these physicians, with
      minor conceptual advances over the centuries. Western medicine separated from
      ancient Indian medicine several hundred years ago, and remains the foundation of
      modern medicine. Modern medicine is evidence based, and randomized clinical
      trials (RCTs) are the gold standard by which efficacy of treatment is evaluated.
      Ayurvedic medicine has not undergone such critical evaluation to any large
      extent. The few RCTs that have evaluated alternative medical treatment recently
      have shown that such therapy is no better than placebo; however, placebo
      treatment is 30% effective. We suggest that foreign domination, initially by
      Mughals, and later by the British, may have contributed, in part, to this inertia
      and protracted status quo.

PMID- 22387656
TI  - Fluticasone furoate: a new intranasal corticosteroid.
AB  - Intranasal corticosteroids are recommended as one of the first-line therapies for
      the treatment of allergic rhinitis (AR), especially when associated with nasal
      congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced
      affinity glucocorticoid for the treatment of AR approved by the Food and Drug
      Administration in 2007 and recently introduced in India. Fluticasone furoate
      nasal spray is indicated for the treatment of the symptoms of seasonal and
      perennial AR in patients aged two years and older. This review summarizes the
      clinical data on fluticasone furoate nasal spray and discusses its role in the
      management of AR. Important attributes of fluticasone furoate include low
      systemic bioavailability (<0.5%), 24-h symptom relief with once-daily dosing,
      comprehensive coverage of both nasal and ocular symptoms, safety and tolerability
      with daily use, and availability in a side-actuated device that makes medication
      delivery simple and consistent. With these properties, fluticasone furoate nasal
      spray has the potential to enhance patient satisfaction and compliance, thus
      making it a good choice amongst available intranasal steroids.

PMID- 22387657
TI  - Organophosphate mumps--additional mechanism.

PMID- 22387658
TI  - Lessons learnt from evaluation of the orientation program for new surgical
      residents using Objective Structured Clinical Examination-based assessment.

PMID- 22387659
TI  - Methotrexate--controversially yours.

PMID- 22387661
TI  - Reevaluating the role of the medial prefrontal cortex in delay eyeblink
      conditioning.
AB  - It has been proposed that the medial prefrontal cortex (mPFC) is not necessary
      for delay eyeblink conditioning (DEC). Here, we investigated the involvement of
      the mPFC in DEC with a soft or loud tone as the conditioned stimulus (CS) by
      using electrolytic lesions or muscimol inactivation of guinea pig mPFC.
      Interestingly, when a soft tone was used as a CS, electrolytic lesions of the
      mPFC significantly retarded acquisition of the conditioned response (CR), and
      muscimol infusions into mPFC distinctly inhibited the acquisition and expression
      of CR, but had no significant effect on consolidation of well-learned CR. In
      contrast, both electrolytic lesions and muscimol inactivation of mPFC produced no
      significant deficits in the CR when a loud tone was used as the CS, or in the
      unconditioned response (UR) when a soft or loud tone was used as the CS. These
      results demonstrate that the mPFC is essential for the DEC with the soft tone CS
      but not for the DEC with the loud tone CS.

PMID- 22387662
TI  - Brain activity associated with omission of an aversive event reveals the effects
      of fear learning and generalization.
AB  - During fear learning, anticipation of an impending aversive stimulus increases
      defensive behaviors. Interestingly, omission of the aversive stimulus often
      produces another response around the time the event was expected. This omission
      response suggests that the subject detected a mismatch between what was predicted
      and what actually occurred, thereby providing an indirect measure of cognitive
      expectancy. Here, we used functional magnetic resonance imaging to investigate
      whether omission-related brain activity reflects fear expectancy during learning
      and generalization of conditioned fear. During conditioning, a face expressing a
      moderate amount of fear (conditioned stimulus, CS+) signaled delivery of an
      aversive shock unconditioned stimulus (US), whereas the same face with a neutral
      expression was unreinforced. In a subsequent generalization test, subjects were
      presented with faces expressing more or less fear intensity than the CS+.
      Psychophysiological results revealed an increase in the skin conductance response
      (SCR) during learning when the US was omitted. Omission-related SCRs were also
      observed during the generalization test following the offset of high- but not low
      intensity face expressions. Neuroimaging results revealed omission-related neural
      activity during learning in the anterior cingulate cortex, parietal cortex,
      insula, and striatum. These same regions also showed omission-related responses
      during the generalization test following highly expressive fearful faces.
      Finally, regression analysis on omission responses during the generalization test
      revealed correlations in offset-related SCRs and neural activity in the
      dorsomedial prefrontal cortex and posterior parietal cortex. Thus, converging
      psychophysiological and neural activity upon omission of aversive stimulation
      provides a novel metric of US expectancy, even to generalized cues that had no
      prior history of reinforcement.

PMID- 22387663
TI  - Severe cutaneous eruptions on telaprevir.

PMID- 22387665
TI  - Cholesterol uptake and hepatitis C virus entry.

PMID- 22387666
TI  - Patients with cirrhosis admitted to an intensive care unit.

PMID- 22387667
TI  - ABCB4/MDR3 gene mutations and cholangiocarcinomas.

PMID- 22387670
TI  - HCV infection, HOMA index and sustained virological response: the step we need to
      take before moving forward.

PMID- 22387671
TI  - Maternal cadmium exposure induces mt2 and smtB mRNA expression in zebrafish
      (Danio rerio) females and their offspring.
AB  - The present study aimed to identify the effects of maternal cadmium (Cd(2+))
      exposure on the mRNA expression of mt2 (metallothionein-2) and smtB (similar to
      metallothionein-B) in female zebrafish (Danio rerio) and their offspring (F1
      larvae). Zebrafish females were exposed to 0, 8.9, 17.8, and 35.6 MUM Cd(2+) for
      72 h, and their ovaries and F1 larvae were collected to measure their Cd(2+)
      contents and their smtB and mt2 mRNA expression. Cd(2+) contents and the mRNA
      expression of smtB and mt2 in F1 larvae all showed positive correlations with the
      maternal Cd(2+) treatment dose. The mt2 was 1.9- to 3.4-fold higher than smtB in
      F1 larvae. Furthermore, F1 larvae had noticeably enhanced Cd(2+) tolerance after
      maternal Cd(2+) treatment. These results demonstrate that maternal Cd(2+) was
      transferred to larval fish and induced mt2 and smtB mRNA expression to protect
      larva against the impacts of Cd(2+). In female ovaries, mt2 expression showed a
      noticeable increase after exposure to a metal environment, while smtB did not
      show exactly the same effect. The study can only conclude that smtB might have a
      much different role other than just protecting against the impacts of metals.

PMID- 22387672
TI  - NAD(P)H quinone oxidoreductase 1 (NQO1) genetic C609T polymorphism is associated
      with the risk of digestive tract cancer:  a meta-analysis based on 21 case
      control studies.
AB  - The relationships between the NAD(P)H quinone oxidoreductase 1 (NQO1) C609T
      polymorphism and the risk of digestive tract (DT) cancer are controversial.
      Therefore, we performed a meta-analysis to assess the relationships. The
      databases of Medline, Embase, and WanFang (updated to 15 May 2011) were reviewed.
      Odds ratios and 95% confidence intervals were calculated to assess the strength
      of the associations. Overall, 21 individual case-control studies in 20 papers
      with 5340 cases and 5911 controls were included in this meta-analysis. The
      results of combined analyses indicated that the T allele of NQO1 C609T was
      significantly associated with increased risk of DT cancer [odds ratio (95% CI):
      1.58 (1.22-2.07) for TT vs. CC and 1.13 (1.06-1.22) for T carriers vs. C
      carriers]. Subgroup analyses for different types of cancers indicated that the T
      allele was significantly associated with an increased risk of gastric cancer
      [1.19 (1.13-1.47) for T carriers vs. C carriers], but not with esophageal cancer
      [1.05 (0.86-1.27) for T carriers vs. C carriers] and colorectal cancer [1.09
      (0.98-1.21) for T carriers vs. CC]. Subgroup analyses for ethnicities and
      countries indicated that the T allele was associated with risk of DT cancer among
      Europeans [1.52 (1.05-2.19) for TT vs. CC] and Asians [1.52 (1.05-2.19) for TT
      vs. CC], and German, Indian, and Chinese populations but not among English and
      Japanese populations. In addition, subgroup analyses also indicated that the T
      allele was significantly associated with risk of DT cancer in studies with large
      and small sample sizes and in population-based studies, but not in hospital-based
      studies. This meta-analysis suggests that NQO1 C609T is significantly associated
      with risk of DT cancer among both Europeans and Asians, especially gastric
      cancer. Because of the limited number of cases and controls in the subgroup
      analyses, more well-designed studies with a large sample of participants are
      needed to verify our findings.

PMID- 22387673
TI  - Incidence of cancer of unknown primary in Sweden:  analysis by location of
      metastasis.
AB  - Increasing incidences of cancer of unknown primary (CUP) have been observed in
      Sweden previously. However, it is not known how the incidence trends for specific
      locations of metastasis vary. Site-specific data are available on the basis of
      the ninth international classification of diseases. CUP patients were identified
      between 1987 and 2008 from the Swedish Family-Cancer Database. Malignant
      neoplasms of ill-defined sites were diagnosed in 4042 patients, 1976 developed
      metastasis in lymph nodes, 9615 had metastasis in specified organs, and in 8052
      patients, the malignant neoplasm was diagnosed without further specification. Age
      standardized incidence rates for 23 685 patients were analyzed using a direct
      method of standardization. Overall, the incidence of CUP decreased from 6.98 to
      6.00 per 100 000 from 1987 to 2008. The number of patients diagnosed with
      metastasis in specified organs decreased, whereas the number of patients
      diagnosed with CUP without further specification increased from 2.65 to 3.02 per
      100 000. With improvements in diagnostic methods and imaging techniques for
      identification of cancer, the incidences of CUP have been decreasing because
      primary tumors can be specified more often. Computed tomography is typically
      sensitive in detecting lung, kidney, and colorectal cancers, which are known to
      have a genetic link with CUP. Prostate-specific antigen testing is used to detect
      prostate cancer, for which bone is a common metastatic site. Liver metastases are
      common if the primary tumor is located in the colorectum. If the primary tumor is
      found, this cancer site replaces the diagnosis of CUP within the Cancer Register
      and therefore CUP incidence is decreased.

PMID- 22387675
TI  - Single administration of GDNF into the striatum induced protection and repair of
      the nigrostriatal dopaminergic system in the intrastriatal 6-hydroxydopamine
      injection model of hemiparkinsonism.
AB  - PURPOSE: Neurotrophic factor delivery into the brain is a promising approach in
      the treatment of Parkinson's disease. Glial cell line-derived neurotrophic factor
      (GDNF) is one of the most potent neurotrophic factors for dopaminergic neurons.
      Although multiple injections of GDNF into the brain are commonly performed in
      experimental studies, the present study investigates the efficacy of using a
      single injection of GDNF, which may be useful in elinically applying this
      treatment. METHODS: Unilateral 6-hydroxydoparnine (6-OHDA) administration into
      the striatum was perforrned in Sprague-Dawley rats to create a partial lesion of
      the nigrostriatal DA system. These parkinsonian model rats received a single
      injection of human recombinant GDNF into the same portion of the striatum either
      24 h before or 4 weeks after 6-OHDA treatrnent. RESULTS: GDNF injected into the
      striatum before 6-OHDA administration potently protected the dopaminergic system,
      as shown by the numbers of mesencephalic dopaminergie neuron cell bodies and
      dopaminergic nerve terminal densities in the striatum. Dopaminergic neuron cell
      bodies and fiber densities were also significantly restored when GDNF was given
      after 6-OHDA administration, although the degree of restoration was lower than in
      the protective experiment. ODNF administration ameliorated apomorphine-induced
      rotational behavior in animals receiving it either before or after 6-OHDA
      treatment. However, the degree of improvement was less prominent when GDNF was
      iniected after 6-OHDA. CONCLUSION: Intracerebral GDNF adininistration exerts both
      protective and regenerative effects on the nigrostriatal dopaminergic system, a
      finding which may have implications for the development of new treatment
      strategies for Parkinson's disease.

PMID- 22387674
TI  - Signaling pathways mediating the neuroprotective effects of sex steroids and
      SERMs in Parkinson's disease.
AB  - Studies with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model
      of Parkinson's disease have shown the ability of 17beta-estradiol to protect the
      nigrostriatal dopaminergic system. This paper reviews the signaling pathways
      mediating the neuroprotective effect of 17beta-estradiol against MPTP-induced
      toxicity. The mechanisms of 17beta-estradiol action implicate activation of
      signaling pathways such as the phosphatidylinositol-3 kinase/Akt and the mitogen
      activated protein kinase pathways. 17beta-estradiol signaling is complex and
      integrates multiple interactions with signaling molecules that act to potentiate
      a protective effect. 17beta-estradiol signaling is mediated via estrogen
      receptors, including GPER1, but others receptors, such as the IGF-1 receptor, are
      implicated in the neuroprotective effect. Glial and neuronal crosstalk is a
      critical factor in the maintenance of dopamine neuronal survival and in the
      neuroprotective action of 17beta-estradiol. Compounds that stimulate GPER1 such
      as selective estrogen receptor modulators and phytoestrogens show neuroprotective
      activity and are alternatives to 17beta-estradiol.

PMID- 22387676
TI  - Interacting effects of aromatic plants and female age on nest-dwelling
      ectoparasites and blood-sucking flies in avian nests.
AB  - Some avian species incorporate aromatic plants to their nests. The "nest
      protection hypothesis", which posits that volatile secondary compounds contained
      in these plants may have antiparasite properties, has not received full support.
      All previous tests of this hypothesis have only considered effects on nest
      dwelling ectoparasites, but not on blood-sucking flies. The "drug hypothesis"
      posits that aromatic plants may stimulate nestling immune system, development, or
      condition. We tested these hypotheses experimentally in wild blue tits, Cyanistes
      caeruleus, a species that adds aromatic plants to their nests. We supplemented
      aromatic plants to half of a sample of nests, while adding grass to the other
      half of nests. We quantified abundance of two groups of blood-sucking flies
      (blackflies and biting midges) at two different stages of the reproductive
      period, and abundance of three nest-dwelling ectoparasites (fleas, mites, and
      blowflies). Experimental supplementation of aromatic plants reduced abundance of
      fleas only in nests of yearling females and not in nests of older females.
      Blackflies and biting midges were both more numerous in nests of yearling females
      than in nests of older females. Mass of aromatic plants added by females was
      negatively related with abundance of fleas in control nests but not in
      experimental nests supplied with aromatic plants. Mass of plants added by females
      was also positively related with abundance of blackflies during the nestling
      stage. Finally, aromatic plants did not affect nestling growth or immune
      responses. We conclude that several factors such as female experience and their
      ability to add plants to the nest interact to explain effects of aromatic plants
      on different parasites.

PMID- 22387677
TI  - Immediate and long-term effects of testosterone on song plasticity and learning
      in juvenile song sparrows.
AB  - Steroid sex hormones play critical roles in the development of brain regions used
      for vocal learning. It has been suggested that puberty-induced increases in
      circulating testosterone (T) levels crystallize a bird's repertoire and inhibit
      future song learning. Previous studies show that early administration of T
      crystallizes song repertoires but have not addressed whether new songs can be
      learned after this premature crystallization. We brought 8 juvenile song sparrows
      (Melospiza melodia) into the laboratory in the late summer and implanted half of
      them with subcutaneous T pellets for a two week period in October. Birds treated
      with T tripled their singing rates and crystallized normal songs in 2 weeks.
      After T removal, subjects were tutored by 4 new adults. Birds previously treated
      with T tended toward learning fewer new songs post T, consistent with the
      hypothesis that T helps to close the song learning phase. However, one T-treated
      bird proceeded to learn several new songs in the spring, despite singing
      perfectly crystallized songs in the fall. His small crystallized fall repertoire
      and initial lag behind other subjects in song development suggest that this
      individual may have had limited early song learning experience. We conclude that
      an exposure to testosterone sufficient for crystallization of a normal song
      repertoire does not necessarily prevent future song learning and suggest that
      early social experiences might override the effects of hormones in closing song
      learning.

PMID- 22387678
TI  - Schottky barrier thin film transistors using solution-processed n-ZnO.
AB  - Solution-processed ZnO thin films are attractive as active materials in thin film
      transistors (TFTs) for low-cost electronic device applications. However, the lack
      of true enhancement mode operation, low mobility, and unreliability in transistor
      characteristics due to the high density of traps and other defects present
      challenges in using such TFTs in circuits. We demonstrate in this report that the
      electrical characteristics of such TFTs can be improved by source injection
      barriers. Asymmetrical Schottky source metal-oxide-semiconductor field-effect
      transistors (MOSFETs) have been fabricated by utilizing heavily doped solution
      processed ZnO as the active layer. n(+)-ZnO was obtained by using triethylamine
      as the stabilizer in the solution process instead of the more commonly used
      monoethanolamine. Au was chosen for source metallization to create a Schottky
      contact to the ZnO and an Al ohmic contact was chosen as the drain. Voltage
      applied to the gate induced field emission through the Schottky barrier and
      allowed modulation of the drain current by varying the width of the barrier. By
      operating the asymmetrical MOSFET when the Schottky contact is reverse biased,
      effective control over the transistor characteristics was obtained.

PMID- 22387679
TI  - Chemiluminescence of CdTe nanocrystals catalyzed by sodium hexametaphosphate and
      its sensitive application for determination of estrogens.
AB  - A novel flow injection nanocrystals (NCs) chemiluminescence (CL) analysis method
      has been established for the determination of estradiol, estriol and estrone
      based on the enhancement of CdTe NCs-KMnO(4) CL reaction catalyzed by sodium
      hexametaphosphate. Glutathione (GSH)-capped CdTe nanocrystals were synthesized in
      aqueous medium, and the CdTe NCs emitted at around 555 nm was selected as the
      light emitter in CdTe NCs-KMnO(4) chemiluminescence (CL) system. It has been
      found that sodium hexametaphosphate (SHMP) enhanced the CL of the CdTe NCs
      KMnO(4) system and estrogens increased these CL signals again in near neutral
      solution. UV-visible spectra, photoluminescence (PL) spectra, transmission
      electron microscopy (TEM) and CL spectra were used to characterize CdTe
      nanoparticles and investigate the mechanism of the CL reaction. On the basis of
      the enhancement, a novel flow-injection CL method has been established for the
      determination of estrogens. Under the optimum experimental conditions, three
      linear relationships were obtained. The method described is simple, sensitive,
      and has been successfully utilized for the determination of estrogens in tap
      water samples.

PMID- 22387680
TI  - Raman spectroscopic study of the mineral arsenogorceixite
      BaAl3AsO3(OH)(AsO4,PO4)(OH,F)6.
AB  - Arsenogorceixite BaAl(3)AsO(3)(OH)(AsO(4),PO(4))(OH,F)(6) belongs to the
      crandallite mineral subgroup of the alunite supergroup. Arsenogorceixite forms a
      continuous series of solid solutions with related minerals including gorceixite,
      goyazite, arsenogoyazite, plumbogummite and philipsbornite. Two minerals from (a)
      Germany and (b) from Ashburton Downs, Australia were analysed by Raman
      spectroscopy. The spectra show some commonality but the intensities of the peaks
      vary. Sharp intense Raman bands for the German sample, are observed at 972 and
      814 cm(-1) attributed to the nu(1) PO(4)(3-) and AsO(4)(3-) symmetric stretching
      modes. Raman bands at 1014, 1057, 1148 and 1160 cm(-1) are attributed to the
      nu(1) PO(2) symmetric stretching mode and nu(3) PO(4)(3-) antisymmetric
      stretching vibrations. Raman bands at 764 and 776 cm(-1) and 758 and 756 cm(-1)
      are assigned to the nu(3) AsO(4)(3-) antisymmetric stretching vibrations. For the
      Australian mineral, the nu(1) PO(4)(3-) band is found at 973 cm(-1). The
      intensity of the arsenate bands observed at 814, 838 and 870 cm(-1) is greatly
      enhanced. Two low intensity Raman bands at 1307 and 1332 cm(-1) are assigned to
      hydroxyl deformation modes. The intense Raman band at 441 cm(-1) with a shoulder
      at 462 cm(-1) is assigned to the nu(2) PO(4)(3-) bending mode. Raman bands at 318
      and 340 cm(-1) are attributed to the (AsO(4))(3-)nu(2) bending. The broad band
      centred at 3301 cm(-1) is assigned to water stretching vibrations and the sharper
      peak at 3473 cm(-1) is assigned to the OH stretching vibrations. The observation
      of strong water stretching vibrations brings into question the actual formula of
      arsenogorceixite. It is proposed the formula is better written as
      BaAl(3)AsO(3)(OH)(AsO(4),PO(4))(OH,F)(6).xH(2)O. The observation of both
      phosphate and arsenate bands provides a clear example of solid solution
      formation.

PMID- 22387681
TI  - The effect of zinc ion on the absorption and emission spectra of glutathione
      derivative: predication by ab initio and DFT methods.
AB  - Relying on the reaction of o-phthalaldehyde (OPA) with glutathione (GSH) to form
      a highly fluorescence derivative GSH-OPA has been widely used to measure reduced
      glutathione. In order to better understand spectra property of the GSH-OPA and
      the effect of zinc ion on it, the ground and the lowest singlet excited state
      properties, the electronic absorption and emission spectra are predicted by ab
      initio and DFT methods. The absorption spectra are simulated using time dependent
      DFT method (TD-DFT) whereas the emission spectra are approximated by optimizing
      the lowest singlet excited state by HF/CI-Singles and then subsequently using
      this geometry for the TD-DFT calculations. The solvent effects on transition
      energies have been described within the conductor-like polarizable continuum
      model (CPCM). The calculated transition energies (absorption and emission) are in
      agreement with available experimental information.

PMID- 22387682
TI  - A vibrational spectroscopic study of plancheite Cu8Si8O22(OH)4.H2O.
AB  - Plancheite Cu(8)Si(8)O(22)(OH)(4).H(2)O is a hydrated copper hydroxy silicate.
      Raman spectroscopy complimented with infrared spectroscopy has been used to
      determine the molecular structure of plancheite. Raman bands at around 1048, 1081
      and 1127 are described as the nu(1)-SiO(3) symmetric stretching vibrations; Raman
      bands at 828, 906 are attributed to the nu(3)-SiO(3) antisymmetric stretching
      vibrations. The Raman band at 699 cm(-1) is assigned to the nu(4) bending modes
      of the -SiO(3) units. The intense Raman band at 3479 cm(-1) is ascribed to the
      stretching vibration of the OH units. The Raman band at 3250 cm(-1) is evidence
      for water in the structure.

PMID- 22387683
TI  - Whelanite Ca5Cu2(OH)2CO3,Si6O17.4H2O--a vibrational spectroscopic study.
AB  - Whelanite Ca(5)Cu(2)(OH)(2)CO(3),Si(6)O(17).4H(2)O is a hydrated hydroxy mixed
      anion compound with both silicate and carbonate anions in the formula. The
      structural characterisation of the mineral whelanite remains incomplete.
      Whelanite is probably a neosilicate with Cu(2+) in square planar coordination.
      Two Raman bands at 1070 and 1094 cm(-1) are assigned to the nu(1) symmetric
      stretching modes of the CO(3)(2-) units. The observation of two symmetric
      stretching modes supports the concept of two non-equivalent CO(3)(2-) units in
      the whelanite structure. The intense sharp Raman band at 1006 cm(-1) is assigned
      to the nu(1) (A(1g)) symmetric stretching vibration of the Si(6)O(17) units. The
      splitting of the nu(3) vibrational mode offers support to the concept that the
      SiO(4) tetrahedron in whelanite is strongly distorted. A very intense Raman band
      observed at 666 cm(-1) with a shoulder at 697 cm(-1) is assigned to the nu(4)
      vibrational modes. Intense Raman bands at 3534, 3556, 3550 and 3595 cm(-1) are
      assigned to the stretching vibrations of the OH units. Low intensity Raman bands
      at 2910, 3187 and 3453 cm(-1) are assigned to water stretching modes. Thus,
      vibrational spectroscopy has been used to characterise the molecular structure of
      whelanite. Whelanite is a mineral that could be conceived as a healing mineral.

PMID- 22387684
TI  - Vibrational spectroscopy and solubility study of the mineral stringhamite
      CaCuSiO4.H2O.
AB  - Stringhamite CaCuSiO(4).H(2)O is a hydrated calcium copper silicate and is
      commonly known as a significant 'healing' mineral and is potentially a semi
      precious jewel. Stringhamite is a neosilicate with Cu(2+) in square planar
      coordination. Vibrational spectroscopy has been used to characterise the
      molecular structure of stringhamite. The intense sharp Raman band at 956 cm(-1)
      is assigned to the nu(1) (A(1g)) symmetric stretching vibration. Raman bands at
      980, 997, 1061 cm(-1) are assigned to the nu(3) (A(2u), B(1g)) antisymmetric
      stretching vibrations. Splitting of the nu(3) vibrational mode supports the
      concept that the stringhamite SiO(4) tetrahedron is strongly distorted. The
      intense bands at 505 and 519 cm(-1) and at 570 cm(-1) are assigned to the nu(2)
      and nu(4) vibrational modes. The question arises as to whether the mineral
      stringhamite can actually function as a healing mineral. An estimation of the
      solubility product at pH<5 shows that the cupric ion can be released. The copper
      ion is a very powerful antibiological agent and thus the mineral stringhamite may
      well function as a healing mineral.

PMID- 22387685
TI  - Synthesis and spectral characterization of ternary mixed-vanadyl beta-diketonate
      complexes with Schiff bases.
AB  - A new method to synthesize some mononuclear ternary oxovanadium(IV) complexes of
      the general formula [VO(beta-dike)(SB)] (where Hbeta-dike=acetylacetone;
      benzoylacetone or dibenzoylmethane, HSB=Schiff bases) has been explored by
      stepwise substitutions of acetylacetonate ion of VO(acac)(2) with Schiff bases.
      The substituted acetylacetone could be fractionated out with p-xylene as an
      azeotrope. The complexes were characterized by elemental analyses, molecular
      weight determinations, spectral (electronic, infrared, (1)H NMR, EPR and powder
      XRD) studies, magnetic susceptibility measurements and cyclic voltammetry. Molar
      conductance measurements indicated the complexes to be non-electrolytes in
      nitrobenzene. Bidentate chelating nature of beta-diketones and Schiff base anions
      in the complexes was established by infrared and NMR spectra. Molecular weight
      determinations confirmed mononuclear nature of the complexes. The EPR spectra
      illustrated coupling of the unpaired electron with (51)V nucleus (I=7/2). Cyclic
      voltammograms of all the complexes displayed two-step oxidation processes. The
      oxidation peak potential corresponded to the quasireversible one-electron
      oxidation process of the metal center, yielding V(V) species. Transmission
      electron microscopy (TEM) indicated spherical particles of ~200 nm diameter. The
      synthesized complexes are mixed-ligand complexes showing a considerable
      hydrolytic stability in which vanadium is having coordination number 5. A square
      pyramidal geometry around vanadium has been assigned in all the complexes.

PMID- 22387686
TI  - Synthesis, characterization and metal ion-sensing properties of two Schiff base
      derivatives.
AB  - Two new Schiff base derivatives {2,2'-diphenyl-N,N'-bis(2
      pyridylmethylene)biphenyl-4,4'-diamine} (1) and {2,2'-diphenyl-N,N'
      bis(salicylidene)biphenyl-4,4'-diamine} (2) were synthesized and characterized by
      means of elemental analysis, (1)H NMR, FT-IR, and standard spectroscopy
      techniques. The molecular structure of 2 has been determined by X-ray single
      crystal analysis. The analyses of fluorescence properties of the compounds
      revealed that 1 and 2 are both poorly fluorescent and display sensitive
      fluorescence responses to a panel of 24 monovalent, divalent, and trivalent metal
      ions in CH(3)CN-DMSO (9:1, v/v). Results with imine 1 showed that Fe(3+), Cu(2+),
      Zn(2+), Cd(2+), Mn(2+), Zr(4+), Hg(2+), Cr(2+), Pb(2+), Sn(2+), Bi(2+), Al(3+),
      Ce(3+), La(3+), Sm(3+), Gd(3+), Nd(3+), Eu(3+) and Dy(3+) yields red shifts in
      emission and increases in intensity. And the greatest spectral changes for imine
      2 include enhancements in emission intensity coupled with red shifts (Zr(4+),
      Sn(2+), Al(3+) and Zn(2+)) and strong quenching (Fe(3+)). The fluorescence
      enhancement mechanism of 1 and 2 for metal ions is based on: (i) CN
      isomerization; (ii) chelation-enhanced fluorescence (CHEF) effect; and (iii)
      excited-state intra/intermolecular proton transfer (ESPT).

PMID- 22387687
TI  - Thermodynamics of the interaction of Pd(dmen)(H2O)22+ with bio-relevant ligands
      with reference to the deactivation of metal-based drug by thiol ligands.
AB  - Pd(dmen)Cl(2) complex was synthesized and characterized, where dmen=N,N
      dimethylethylenediamine. Stoichiometry and stability constants of the complexes
      formed between [Pd(dmen)(H(2)O)(2)](2+) and various biologically relevant ligands
      such as amino acids, peptides and dicarboxylic acids are investigated at 25 
      degrees C and at constant 0.1M ionic strength. The concentration distribution
      diagrams of the various species formed are evaluated. The equilibrium constants
      for the displacement of coordinated ligands as inosine, glycine or methionine by
      cysteine are calculated. The results are expected to contribute to the chemistry
      of tumour therapy.

PMID- 22387690
TI  - Quantifying the association between tuberculosis and diabetes in the US: a case
      control analysis.
AB  - Historically, an association between tuberculosis and diabetes was recognised
      clinically, and the recent global rise in diabetes prevalence has reignited
      interest. We therefore quantified the tuberculosis-diabetes association using US
      survey data. A case-control analysis was performed using cross-sectional data
      from the second National Health and Nutrition Examination Survey (1976-1980;
      civilian non-institutionalised US population aged 20-74). Cases were respondents
      ever diagnosed with tuberculosis, and controls were respondents who reported
      never receiving a tuberculosis diagnosis. Exposure to diabetes and intermediate
      hyperglycaemia was defined using a self-reported measure, an oral glucose
      tolerance test, or both. We used logistic regression to estimate an adjusted odds
      ratio, controlling for potential major confounders. In relation to the main
      exposure measure, the adjusted odds ratio for the association between
      tuberculosis and diabetes varied between 2.31 (95% confidence interval 1.36-3.93)
      and 2.36 (95% confidence interval 1.40-3.97), depending on the model. No
      association was found for intermediate hyperglycaemia, with adjusted odds ratio
      varying between 1.33 (95% confidence interval 0.49-3.64) and 1.34 (95% confidence
      interval 0.50-3.62), depending on model. Irrespective of the exposure measure and
      the confounders controlled for, diabetes was associated with an increased
      tuberculosis risk. This study may underestimate the true association due to
      exposure misclassification.

PMID- 22387691
TI  - Understanding the context of patient experiences in order to explore adherence to
      secondary prevention guidelines after heart surgery.
AB  - After coronary artery bypass surgery, many patients do not incorporate healthy
      behaviors into their postoperative lifestyle or enroll in cardiac rehabilitation,
      key aspects of secondary prevention. This qualitative study examined patients'
      post-coronary artery bypass surgery experiences to explore barriers in adhering
      to dietary and activity guidelines. We conducted semi-structured, in-depth
      interviews with 30 male patients from a military veteran's hospital, using
      emergent, thematic analysis to identify experiences that led to poor adherence.
      RESULTS were grouped according to barriers to diet, activities, and enrolling in
      cardiac rehabilitation. Overall, understandings of postoperative health,
      priorities that diverged from guidelines, and the context of household members
      and other health conditions impacted postoperative health behaviors. Many
      participants were familiar with secondary prevention guidelines. However,
      postoperative perceptions of health as well as the context of recovery influenced
      self-management. Providers must consider a patient's context when discussing
      secondary prevention. Venues such as cardiac rehabilitation may provide an
      opportunity to improve adherence to secondary prevention guidelines by expanding
      available class times, engaging patients' household members, or tailoring
      recommendations to also address other health conditions.

PMID- 22387692
TI  - Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR
      24.
AB  - Aryl hydrocarbon receptor nuclear translocator (ARNT) forms a heterodimer with
      aryl hydrocarbon receptor or hypoxia inducible factor 1alpha to mediate
      biological responses to xenobiotic exposure and hypoxia. Although the regulation
      mechanism of the ARNT expression is largely unknown, earlier studies reported
      that the human ARNT protein level was decreased by hydrogen peroxide or reactive
      oxygen species. These stimuli increase the miR-24 level in various human cell
      lines. In silico analysis predicts that some microRNAs including miR-16 and miR
      23b may bind to ARNT mRNA. This background prompted us to investigate whether
      human ARNT is regulated by microRNAs. Overexpression of miR-24 into HuH-7 and
      HepG2 cells significantly decreased the ARNT protein level, but not the ARNT mRNA
      level, indicating translational repression. However, overexpression of miR-16 or
      miR-23b caused no change in the ARNT expression. The miR-24-dependent down
      regulation of ARNT decreased the expression of its downstream genes such as
      CYP1A1 and carbonic anhydrase IX. Luciferase assay was performed to determine the
      element on the ARNT mRNA to which miR-24 binds. Finally, it was demonstrated that
      the miR-24 levels in a panel of 26 human livers were inversely correlated with
      the protein levels or the translational efficiency of ARNT. Taken together, we
      found that miR-24 negatively regulates ARNT expression in human liver, affecting
      the expression of its downstream genes. miR-24 would be one of the factors
      underlying the mechanisms by which ARNT protein is decreased by reactive oxygen
      species.

PMID- 22387693
TI  - Journal of Alzheimer's disease established as a leading journal.

PMID- 22387694
TI  - Differential efficacy of lipophilic and cytosolic antioxidants on generation of
      reactive oxygen species by amyloid-beta.
AB  - Exposure of neurons to amyloid-beta (Abeta) is accompanied by a cascade of
      oxidative damage that initiates with lipid peroxidation followed by subsequent
      generation of cytosolic free radicals and reactive oxygen species (ROS). The
      antioxidant vitamin E has been utilized to counteract Abeta-induced oxidative
      stress. We considered herein whether or not the lipid-solubility of vitamin E
      limits its neuroprotection to membrane-related oxidative damage, and renders it
      relatively ineffective where prior lipid peroxidation has already generated
      cytosolic free radicals and ROS. To test this possibility, we treated
      differentiated SH-SY-5Y human neuroblastoma with vitamin E or a cell-permeant
      antioxidant, N-acetyl cysteine (NAC), simultaneously with or 15 min after the
      application of Abeta. Both vitamin E and NAC prevented Abeta-induced ROS
      generation when applied simultaneously with Abeta, but only NAC prevented Abeta
      induced ROS generation when added to cultures that had previously been exposed to
      Abeta. These results support the hypothesis that vitamin E can quench Abeta
      induced lipid peroxidation, but cannot effectively quench ROS generated by prior
      lipid peroxidation. These findings in cell culture may provide limited insight
      into why vitamin E is not fully effective against neurodegeneration in AD in
      clinical settings, since some neuronal populations are likely to already have
      been compromised by prior Abeta exposure before vitamin E treatment was
      initiated.

PMID- 22387695
TI  - CSF Abeta40 and Abeta42: Natural course and clinical usefulness.

PMID- 22387699
TI  - Brucella abortus induces apoptosis of human T lymphocytes.
AB  - Immune evasion is essential for Brucella abortus to survive in the face of robust
      adaptive CD4+ T cell response. We have previously demonstrated that B. abortus
      can indirectly inhibit CD4+ T cells by down-regulating MHC-II expression and
      antigen presentation on macrophages. However, whether B. abortus is able to
      directly interfere with T lymphocytes is not known. We report here that B.
      abortus induces apoptosis of human T lymphocytes, even though invasion of T
      lymphocytes was low and non-replicative. The ability of heat-killed B. abortus to
      reproduce the same phenomenon suggested that there was a bacterial structural
      component involved. We demonstrated that a prototypical B. abortus outer membrane
      lipoprotein (l-Omp19), but not its unlipidated form, induced T lymphocyte
      apoptosis. Moreover, a synthetic lipohexapeptide that mimics the structure of the
      protein lipid moiety also induced an increase in T lymphocyte cell death,
      indicating that the structural component implicated in the phenomenon could be
      any B. abortus lipoprotein. B. abortus-induced T lymphocyte apoptosis was
      dependent on the secretion of TNF-alpha since pre-incubation of T lymphocytes
      with anti-TNF-alpha mAb inhibited the apoptosis of the cells. Overall, these
      results represent a new mechanism whereby B. abortus by directly inhibiting T
      cell-mediated responses may evade adaptive immune responses.

PMID- 22387700
TI  - Ontogenic pattern of nucleobindin-2/nesfatin-1 expression in the
      gastroenteropancreatic tissues and serum of Sprague Dawley rats.
AB  - Nesfatin-1 is a novel metabolic hormone that has glucose-responsive
      insulinotropic actions. Islet beta-cells and gastrointestinal tissues have been
      reported as abundant sources of nesfatin-1 and its precursor hormone nucleobindin
      2 (NUCB2). While nesfatin-1 is emerging as a multifunctional hormone, there are
      no reports on the developmental expression of NUCB2/nesfatin-1. The main
      objective of this study was to examine the ontogenic expression of NUCB2 mRNA,
      and NUCB2/nesfatin-1 immunoreactivity in the pancreas, stomach and duodenum, and
      the circulating levels NUCB2/nesfatin-1 in Sprague Dawley rats. In addition, we
      also determined the co-localization of NUCB2/nesfatin-1 and insulin
      immunoreactivity during development. NUCB2/nesfatin-1 immunoreactivity was found
      in the rat stomach from postnatal days 13-27. Furthermore, NUCB2/nesfatin-1
      immunoreactivity was also detected in the enteroendocrine cells of the duodenum
      at postnatal days 13 and 27. Duodenal NUCB2 mRNA expression at postnatal day 27
      was highest. Serum NUCB2/nesfatin-1 levels on embryonic day 21 and postnatal day
      1 were lower than serum NUCB2/nesfatin-1 levels of adults and neonates at
      postnatal days 13, 20 and 27, gradually increasing with growth, suggesting an
      increase in its production and secretion from tissues including the
      gastrointestinal tract and pancreas. Our findings indicate that NUCB2/nesfatin-1
      colocalizes with insulin in the islet beta-cells at all developmental stages, but
      the percentage of colocalization varies in an age-dependent manner. These
      findings suggest that NUCB2/nesfatin-1 has potential age- and tissue-specific
      role in the developmental physiology of rats during growth.

PMID- 22387701
TI  - Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2
      diabetes mellitus.
AB  - OBJECTIVE: Weight gain and obesity are of substantial importance for the
      development of insulin-resistance and type-2 diabetes mellitus. Fetuin-A, a liver
      derived glycoprotein, may also play a role in these alterations. Several studies
      have demonstrated an association between fetuin-A and body weight which, however,
      was within a fairly small range at the border of overweight to obesity. The
      present study examines the relationship between fetuin-A and a wide range of BMI,
      together with basal insulin, and HOMA-IR. In addition, matched groups of non
      diabetic patients and those with type-2 diabetes mellitus were compared. METHODS:
      We examined the relationship between fetuin-A and BMI, insulin, HOMA-IR, glucose
      and HbA1c in a cohort of 445 non-diabetic obese subjects and 150 obese patients
      with type-2-diabetes mellitus (DM2). RESULTS: In relation to quintiles of fetuin
      A a significant increase of BMI, basal insulin and HOMA-IR was observed between
      the 1st and 2nd quintile with no further change thereafter. Correspondingly,
      fetuin-A levels increased significantly only between the 1st and 2nd quintile of
      BMI, insulin or HOMA-IR, respectively. When patients with type 2 diabetes were
      compared with non-diabetic subjects matched for BMI, insulin, and age median
      fetuin-A levels were not significantly different. CONCLUSION: At the early stage
      of weight gain fetuin-A could be of relevance for the development of insulin
      resistance. For the further progressive resistance with increasing weight in the
      obesity range the present data do not support a role of fetuin-A. Similarly its
      contribution to the resistance of type-2 diabetes seems to be of minor
      importance.

PMID- 22387702
TI  - Circulating ghrelin and GLP-1 are not affected by habitual diet.
AB  - BACKGROUND: Ghrelin and glucagon-like peptide-1 (GLP-1) are gut hormones known to
      induce hunger and satiety, respectively. Current knowledge about the effects of
      different macronutrients on circulating ghrelin and GLP-1 comes mainly from acute
      test meals, whereas little is known about the effects of chronic dietary intake
      on gut hormone secretion. This study was designed to examine whether 8-week
      habituation to diets with different percentages of carbohydrate and fat would
      affect serum ghrelin, GLP-1, and subjective hunger in a postabsorptive state and
      in response to a standard liquid mixed meal. METHODS: Sixty-one overweight men
      and women were provided all food for 8 weeks of either a higher
      carbohydrate/lower-fat diet (High-CHO/Low-FAT; 55% CHO, 18% PRO, 27% FAT) or a
      lower-carbohydrate/higher-fat diet (Low-CHO/High-FAT; 43% CHO, 18% PRO, 39% FAT).
      After overnight fasts at baseline and week 8, participants consumed a standard
      liquid meal (7 kcals/kg, 58.6% CHO, 17.4% PRO, 24% FAT). Blood was sampled before
      the meal and at 15, 60, 90, 120, 180, and 240 min to determine total serum
      ghrelin and active GLP-1. Hunger was assessed by a visual analog scale. Mixed
      models were used to evaluate whether the temporal patterns of total serum ghrelin
      and active GLP-1 differed with diet. RESULTS: Although both diet groups reported
      greater hunger after 8 weeks (p=0.03), circulating ghrelin and GLP-1 were not
      affected by acclimation to different macronutrients. CONCLUSION: Habituation to
      different diets does not appear to influence fasting ghrelin, fasting GLP-1, or
      responses of these gut hormones to a standard meal.

PMID- 22387703
TI  - Molecular and morphometric analysis of the rat ventral prostate injected with
      leptin.
AB  - The aim of this study was to evaluate the effect of leptin administration on the
      ventral prostate lobe of adult rat. Twenty adult male rats were divided into 2
      groups: L-animals were daily injected with 50 MUL of leptin (8 MUg/100 g BW,
      subcutaneous) for four days and C-animals received the same volume of saline
      solution. Lipid profile and testosterone serum levels were evaluated. The
      prostate ventral lobe was processed for histomorphometric analysis. Gene
      expression of aromatase, androgen, leptin and estrogen receptors isoforms was
      evaluated by real-time PCR. Cell proliferation was evaluated by PCNA
      immunohistochemistry. Data were expressed as mean+/-standard error and analyzed
      by student's t-test. Serum levels of cholesterol (C=39.7+/-4.2;L=55.2+/-4.2,
      mg/dL; P<0.02) increased and testosterone (C=1.6+/-0.43;L=0.6+/-0.15, ng/dL;
      P<0.03) decreased in L group. The histomorphometric analysis showed a reduction
      in cell density (C=8868+/-242; L=8211+/-210, mm(2); P<0.04), in total (C=0.24+/
      0.026; L=0.10+/-0.009, mm(2); P<0.001) and in the internal acini areas (C=0.16+/
      0.009; L=0.08+/-0.006, mm(2); P<0.0002). On the other hand, there was an increase
      in the epithelial height (C=17.3+/-0.3; L=22.8+/-0.2, MUm; P<0.0001) and in the
      number of acini (C=7.0+/-0.2; L=8.7+/-0.1, mm(2); P<0.0002). The
      histomorphometric analyses together with PCNA immunohistochemistry results
      suggest that leptin increases cell proliferation. In relation to the gene
      expression, leptin treatment increased the expression of all genes, but ER-alpha,
      in more than 200 times compared to the expression in C group. In conclusion, in
      this paper we showed that leptin has a direct effect on the prostate gland of
      adult rats leading to an increase in proliferation and in the gene expression of
      aromatase, androgen, leptin and estrogen receptors isoforms that are important
      for the physiology of the prostate gland.

PMID- 22387704
TI  - Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to
      body weight regulation.
AB  - Loss and disproportionate gain of body weight often seen respectively in smokers
      and quitters are believed to be due to disrupted energy homeostasis induced by
      nicotine, the major constituent of cigarette smoke. Energy homeostasis is
      suggested to be regulated by the coordinated actions of peripheral adipose tissue
      derived leptin and the brain hypothalamic orexigenic neuropeptide Y (NPY). While
      the studies probing the role of leptin and NPY in weight modulating effect of
      nicotine have so far been inconsistent and based largely on animal systems, there
      is a paucity of data involving human subjects. Here we measured the plasma levels
      of orexigenic neuropeptide Y (NPY) and leptin in 35 non-smokers and 31 cigarette
      smokers before and three months after smoking cessation. Compared to non-smokers,
      smokers were leaner and had reduced NPY and leptin levels. Smoking cessation
      resulted in a significant weight gain and increased waist circumference
      accompanied by increased leptin and NPY levels. NPY levels were significantly
      correlated with body weight (r=0.43, p<0.05), BMI (r=0.41, p<0.05), and waist
      circumference (r=0.37, p<0.05), while leptin correlated with BMI (r=0.42, p<0.05)
      and waist circumference (r=0.39, p<0.05). Association of leptin with smoking
      status, but not that of NPY, was lost after controlling for anthropometric
      parameters. Weight modulating effect of cigarette smoke may thus involve its
      direct action on NPY, independent of leptin. Altered leptin levels in smokers and
      quitters may merely reflect changes in body weight or precisely fat mass.

PMID- 22387705
TI  - Cytotoxicity and structure activity relationship studies of maplexins A-I,
      gallotannins from red maple (Acer rubrum).
AB  - Maplexins A-I are a series of structurally related gallotannins recently isolated
      from the red maple (Acer rubrum) species. They differ in number and location of
      galloyl derivatives attached to 1,5-anhydro-glucitol. Here, maplexins A-I were
      evaluated for anticancer effects against human tumorigenic (colon, HCT-116;
      breast, MCF-7) and non-tumorigenic (colon, CCD-18Co) cell lines. The maplexins
      which contained two (maplexins C-D) or three (maplexins E-I) galloyl derivatives
      each, inhibited cancer cell growth while those with only one galloyl group
      (maplexins A-B) did not. Moreover, maplexins C-D showed greater antiproliferative
      effects than maplexins E-I (IC(50)=59.8-67.9 and 95.5-108.5 MUM vs. 73.7-165.2
      and 115.5-182.5 MUM against HCT-116 and MCF-7 cells, respectively). Notably, the
      cancer cells were up to 2.5-fold more sensitive to the maplexins than the normal
      cells. In further mechanistic studies, maplexins C-D (at 75 MUM concentrations)
      induced apoptosis and arrested cell cycle (in the S-phase) of the cancer cells.
      These results suggest that the number of galloyl groups attached to the 1,5
      anhydro-glucitol moiety in these gallotannins are important for antiproliferative
      activity. Also, this is the first in vitro anticancer study of maplexins.

PMID- 22387706
TI  - The role of rehearsal in a novel call center-type task.
AB  - Laboratory research has long demonstrated the disruptive effects of background
      sound to task performance yet the real-world implications of such effects are
      less well known. We report two experiments that demonstrate the importance of the
      role of rehearsal to a novel call center-type task. In Experiment 1, performance
      of a novel train timetable task-in which participants identified four train
      journeys following presentation of train journey information-was disrupted by
      realistic office noise. However, in Experiment 2, when the need for rehearsal was
      reduced by presenting the information and the timetable at the same time, no
      disruption occurred . Results are discussed in terms of interference-by-process
      and interference-by-content approaches to short-term memory.

PMID- 22387707
TI  - Audiological and electrophysiological assessment of professional pop/rock
      musicians.
AB  - In the present study, we evaluated peripheral and central auditory pathways in
      professional musicians (with and without hearing loss) compared to non-musicians.
      The goal was to verify if music exposure could affect auditory pathways as a
      whole. This is a prospective study that compared the results obtained between
      three groups (musicians with and without hearing loss and non-musicians). Thirty
      two male individuals participated and they were assessed by: Immittance
      measurements, pure-tone air conduction thresholds at all frequencies from 0.25 to
      20 kHz, Transient Evoked Otoacoustic Emissions, Auditory Brainstem Response
      (ABR), and Cognitive Potential. The musicians showed worse hearing thresholds in
      both conventional and high frequency audiometry when compared to the non
      musicians; the mean amplitude of Transient Evoked Otoacoustic Emissions was
      smaller in the musicians group, but the mean latencies of Auditory Brainstem
      Response and Cognitive Potential were diminished in the musicians when compared
      to the non-musicians. Our findings suggest that the population of musicians is at
      risk for developing music-induced hearing loss. However, the electrophysiological
      evaluation showed that latency waves of ABR and P300 were diminished in
      musicians, which may suggest that the auditory training to which these musicians
      are exposed acts as a facilitator of the acoustic signal transmission to the
      cortex.

PMID- 22387708
TI  - Validity of hearing impairment calculation methods for prediction of self
      reported hearing handicap.
AB  - Worker's compensation for hearing loss caused by occupational noise exposure is
      calculated by varying methods, from state to state within the United States (US),
      with many employing arithmetic formulas based on the pure-tone audiogram, to
      quantify hearing loss. Several assumptions unsupported or weakly supported by
      empirical data underlie these formulas. The present study evaluated the ability
      of various arithmetic hearing impairment calculations to predict a self-reported
      hearing handicap in a sample of presenting with sensorineural hearing loss. 204
      adults (127 male, 77 female) ranging in age from 18 to 94 served as participants.
      The sample was selected to exclude patients who had been referred for hearing
      testing for a medicolegal examination or a hearing conservation appointment. A
      hearing handicap was measured by the Hearing Handicap Inventory for Adults/for
      the Elderly (HHIA/E). The covariance analysis of linear structural equations was
      used to assess the relative strength of correlation with the HHIA/E score among
      the six formulas and various forms of pure-tone average. The results revealed
      that all the hearing impairment calculations examined were significantly, but
      weakly, correlated with the self-reported hearing impairment scores. No
      significant differences among the predictive abilities of the impairment
      calculations were evident; however, the average binaural impairment assigned
      differed significantly among the six calculations examined. Individuals who
      demonstrated 0% impairment had significantly lower (i.e., better) HHIA/E scores
      compared to those with non-zero impairment for each formula. These results
      supported the idea that audiometric data provided an insufficient explanation for
      real-world hearing difficulties.

PMID- 22387709
TI  - Tracking occupational hearing loss across global industries: a comparative
      analysis of metrics.
AB  - Occupational hearing loss is one of the most prevalent occupational conditions;
      yet, there is no acknowledged international metric to allow comparisons of risk
      between different industries and regions. In order to make recommendations for an
      international standard of occupational hearing loss, members of an international
      industry group (the International Aluminium Association) submitted details of
      different hearing loss metrics currently in use by members. We compared the
      performance of these metrics using an audiometric data set for over 6000
      individuals working in 10 locations of one member company. We calculated rates
      for each metric at each location from 2002 to 2006. For comparison, we calculated
      the difference of observed-expected (for age) binaural high-frequency hearing
      loss (in dB/year) for each location over the same time period. We performed
      linear regression to determine the correlation between each metric and the
      observed-expected rate of hearing loss. The different metrics produced discrepant
      results, with annual rates ranging from 0.0% for a less-sensitive metric to more
      than 10% for a highly sensitive metric. At least two metrics, a 10dB age
      corrected threshold shift from baseline and a 15dB nonage-corrected shift metric,
      correlated well with the difference of observed-expected high-frequency hearing
      loss. This study suggests that it is feasible to develop an international
      standard for tracking occupational hearing loss in industrial working
      populations.

PMID- 22387710
TI  - Amplitude changes in otoacoustic emissions after exposure to industrial noise.
AB  - Noise-induced hearing loss (NIHL) is a frequent problem in industrial settings,
      especially where a high noise level is present. It is permanent, and
      irreversible, but preventable. Routine audiometry (an objective and time
      consuming) test is used for NIHL screening. Otoacoustic emissions (OAEs) are
      recently proposed as a more sensitive test for early diagnosis of NIHL. In this
      study, we aimed to compare the results of pure tone audiometry (PTA) with OAE in
      the diagnosis of NIHL. In a cross-sectional study on 120 workers (in three
      groups: Not exposed to noise, exposed to noise without NIHL and exposed to noise
      with NIHL), we compared the results of PTA and OAE. OAE can detect some changes
      in the function of hearing system in subjects exposed to noise, and these changes
      are apparently prior to hearing loss, which is diagnosed by PTA. OAE is a more
      sensitive method for the early diagnosis of cochlear damage than PTA, and can be
      performed in industrial settings for NIHL screening.

PMID- 22387711
TI  - Validation of a questionnaire to identify hearing loss among farm operators.
AB  - Workers in certain industries (e.g., agriculture) do not participate in a hearing
      conservation program and rarely receive this important preventive care. The
      National Institute for Deafness and Communication Disorders (NIDCD) has published
      a questionnaire to assess a person's need for medical examination of their
      hearing. The use of a self-administered questionnaire may pose a simple, low cost
      opportunity to assess the hearing health of workers not included in a hearing
      conservation program. However, the validity of the NIDCD questionnaire has not
      been tested. A study was conducted to compare the results of audiometric
      screening and the NIDCD questionnaire in identifying persons at risk for hearing
      impairment who may benefit from a medical referral. Data were collected from 103
      farm operators at a regional farm show. Receiver-operator characteristic curves,
      measuring the ability of the questionnaire to correctly classify those with and
      without the disease suggested that the level of performance of the questionnaire
      as a whole, ranged from 0.74 to 0.69 (fair to poor). However, selected
      questionnaire items (e.g., Do you have to strain to understand conversations?)
      had moderate agreement (0.38 to 0.41) with screening audiogram results. Overall,
      the 10-item instrument did not perform as well as instruments with fewer items
      reported in separate studies. These findings suggest that, while less desirable
      than audiometry, alternative self-administered instruments might perform the
      better in this group. This approach may be useful as an alternative screening
      method to detect risk of hearing loss and identifying the need for medical
      evaluation of hearing sensitivity, particularly among farm operators.

PMID- 22387712
TI  - The effect of a hearing conservation program on adolescents' attitudes towards
      noise.
AB  - Crandell et al., reported that education programs such as hearing conservation
      programs (HCPs) represent the most common and well-recognized procedure in
      reducing the incidence of noise-induced hearing loss (NIHL). The purpose of this
      study was to assess the effectiveness of an HCP in changing knowledge and
      attitudes toward exposures to high intensity sounds or noise among adolescents
      aged 12-14 years. Local middle school students in physical education classes were
      recruited for participation. Sixty-four middle school students between the ages
      of 12 and 14 received pre- and post-test measures and participated in the HCP.
      The pre-test measure had 24 questions that included 5 demographic questions and
      19 Likert-type questions [modified from the Youth Attitude to Noise Scale] that
      assess adolescents' attitudes towards noise; and a post-test measure included the
      identical 24 questions of the pre-test measure in addition to three subjective
      questions. A Wilcoxon signed rank test and a Two-Factor Analysis of Variance were
      completed to assess changes in knowledge and attitudes toward noise among the
      study population after receiving the HCP. A statistically significant reduction
      (P< 0.003) in pro-noise attitudes among the adolescents was present after the
      intervention. It was established that an HCP facilitated a change in pro-noise
      attitudes among adolescents. Further, the students thought this program
      facilitated learning of the auditory system and healthy hearing behaviors.

PMID- 22387713
TI  - Fasting for 24 h improves nasal chemosensory performance and food palatability in
      a related manner.
AB  - Changes in smell function can modify feeding behaviour but there is little
      evidence of how acute negative energy balance may impact olfaction and
      palatability. In a within-subjects repeated measures design, 15 subjects (nine
      male; six female) aged 28.6+/-4.5 years with initial body weight (BW) 74.7+/-4.9
      kg and body mass index (BMI) 25.3+/-1.4 kg/m(2) were randomized and tested at
      baseline (FED) and Post Deprivation (FASTED) for nasal chemosensory performance
      (Sniffin' Sticks) and food palatability (visual analogue scale). Significant main
      effects for time indicated improvements in the FASTED session for odor threshold,
      odor discrimination, and total odor scores (TDI), and for increased palatability.
      There were significant positive correlations between initial BW and the change in
      odor threshold (r=.52) and TDI scores (r=.53). Positive correlations were also
      noted between delta identification score and delta palatability (r=.68). When the
      sample was split by sex, only for females were there significant correlations
      between delta palatability and: delta BW (r=.88); delta odor identification
      (r=.94); and delta TDI score (r=.85). Fasting for 24h improved smell function and
      this was related to increased palatability ratings and initial BW. Further
      studies should confirm the role of BW and sex in the context of olfaction, energy
      deprivation and palatability.

PMID- 22387714
TI  - Contaminated and uncontaminated feeding influence perceived intimacy in mixed-sex
      dyads.
AB  - It was expected that viewers watching adult mixed-sex pairs dining together will
      give higher ratings of the perceived intimacy and involvement of the pair if
      feeding is displayed while eating, especially if the feeding involves
      contaminated (i.e., with potential germ transfer) foods. Our hypotheses were
      tested using a design in which participants viewed five videotapes in varying
      order. Each video showed different mixed-sex pairs of actors sharing meal and
      included a distinct form of food sharing or none. These were shown to 50 small
      groups of young adults in quasi-random sequences to control for order effects.
      Immediately after each video, viewers were asked about the attractiveness,
      attraction and intimacy in the dyad they had just observed. As predicted, videos
      featuring contaminated feeding consistently produced higher ratings on
      involvement and attraction than those showing uncontaminated feeding which, in
      turn, mostly produced higher ratings on involvement and attraction than those
      showing no feeding behaviors.

PMID- 22387715
TI  - To eat or not to eat. A comparison of current and former animal product limiters.
AB  - In this exploratory study, we compared current and former pescatarians,
      vegetarians and vegans on a number of variables including the motivations for
      their food choices. Participants were recruited via online message boards as well
      as through snowball sampling. Of the 247 participants, 196 were currently
      limiting animal products and 51 were former animal product limiters. Current
      limiters were more likely to have made a gradual rather than abrupt transition to
      animal product limitation and were more likely to have joined a vegetarian or
      vegan group than former limiters. Furthermore, current limiters indicated that
      their eating pattern was a part of their self identity. These findings shed light
      on the differences among current and former vegans and vegetarians and can inform
      individuals interested in promoting animal product limitation for health or
      ethical reasons.

PMID- 22387716
TI  - Negative affect and neural response to palatable food intake in bulimia nervosa.
AB  - Binge eating is often preceded by reports of negative affect, but the mechanism
      by which affect may lead to binge eating is unclear. This study evaluated the
      effect of negative affect on neural response to anticipation and receipt of
      palatable food in women with bulimia nervosa (BN) versus healthy controls. We
      also evaluated connectivity between the amygdala and reward-related brain
      regions. Females with and without BN (n=26) underwent functional magnetic
      resonance imaging (fMRI) during receipt and anticipated receipt of chocolate
      milkshake and a tasteless solution. We measured negative affect just prior to the
      scan. Women with BN showed a positive correlation between negative affect and
      activity in the putamen, caudate, and pallidum during anticipated receipt of
      milkshake (versus tasteless solution). There were no significant relations
      between negative affect and receipt of milkshake. Connectivity analyses revealed
      a greater relation of amygdala activity to activation in the left putamen and
      insula during anticipated receipt of milkshake in the bulimia group relative to
      the control group. The opposite pattern was found for the taste of milkshake; the
      control group showed a greater relation of amygdala activity to activation in the
      left putamen and insula in response to milkshake receipt than the bulimia group.
      Results show that as negative affect increases, so does responsivity of reward
      regions to anticipated intake of palatable food, implying that negative affect
      may increase the reward value of food for individuals with bulimia nervosa or
      that negative affect has become a conditioned cue due to a history of binge
      eating in a negative mood.

PMID- 22387722
TI  - Case series: CSF LDH, proteins and electrolyte levels in patients of acute
      lymphocytic leukemia.
AB  - BACKGROUND: Central nervous system (CNS) involvement is common in hemoncologic
      diseases especially in patients with acute lymphocytic leukemia (ALL). Currently
      available modalities have limitations in diagnosing CNS involvement in early
      stages of disease and have a limited prognostic value. Raised cerebrospinal fluid
      (CSF) total lactate dehydrogenase (LDH) levels can predict CNS involvement in
      patients with various neurological disorders including CNS leukemia. METHODS:
      This study was conducted in 23 consecutive freshly diagnosed patients of ALL
      without any previous CNS disease. Analysis of CSF was done for total LDH,
      proteins and electrolytes in all the patients before the start of chemotherapy
      and when the patients were in remission or 6 weeks after chemotherapy whichever
      was earlier. Twenty-three age and sex matched controls were also studied to set
      the normal reference range. The results were analyzed statistically by Student's
      t test and coefficient of co-relation between CSF LDH and protein in patients
      with raised CSF LDH at the time of presentation was also calculated. RESULTS: CSF
      LDH was increased in 4 out of 6 patients with signs and symptoms of CNS
      involvement (Group A) and 3 of these patients also had increased CSF protein
      levels. 2 out of 17 patients without signs and symptoms of CNS involvement (Group
      B) had both elevated CSF LDH and protein levels. The increased levels came down
      to normal reference values after chemotherapy except in one Group A patient in
      whom CSF LDH remained high. However, no significant change in CSF electrolytes
      was noted in these patients. CONCLUSION: Raised CSF LDH and CSF protein levels
      may indicate CNS involvement in patients with ALL.

PMID- 22387723
TI  - (Pea)nuts and bolts of visual narrative: structure and meaning in sequential
      image comprehension.
AB  - Just as syntax differentiates coherent sentences from scrambled word strings, the
      comprehension of sequential images must also use a cognitive system to
      distinguish coherent narrative sequences from random strings of images. We
      conducted experiments analogous to two classic studies of language processing to
      examine the contributions of narrative structure and semantic relatedness to
      processing sequential images. We compared four types of comic strips: (1) Normal
      sequences with both structure and meaning, (2) Semantic Only sequences (in which
      the panels were related to a common semantic theme, but had no narrative
      structure), (3) Structural Only sequences (narrative structure but no semantic
      relatedness), and (4) Scrambled sequences of randomly-ordered panels. In
      Experiment 1, participants monitored for target panels in sequences presented
      panel-by-panel. Reaction times were slowest to panels in Scrambled sequences,
      intermediate in both Structural Only and Semantic Only sequences, and fastest in
      Normal sequences. This suggests that both semantic relatedness and narrative
      structure offer advantages to processing. Experiment 2 measured ERPs to all
      panels across the whole sequence. The N300/N400 was largest to panels in both the
      Scrambled and Structural Only sequences, intermediate in Semantic Only sequences
      and smallest in the Normal sequences. This implies that a combination of
      narrative structure and semantic relatedness can facilitate semantic processing
      of upcoming panels (as reflected by the N300/N400). Also, panels in the Scrambled
      sequences evoked a larger left-lateralized anterior negativity than panels in the
      Structural Only sequences. This localized effect was distinct from the N300/N400,
      and appeared despite the fact that these two sequence types were matched on local
      semantic relatedness between individual panels. These findings suggest that
      sequential image comprehension uses a narrative structure that may be independent
      of semantic relatedness. Altogether, we argue that the comprehension of visual
      narrative is guided by an interaction between structure and meaning.

PMID- 22387724
TI  - Cerebral aneurysm wall thickness analysis using intraoperative microscopy: effect
      of size and gender on thin translucent regions.
AB  - OBJECTIVE: Wall thickness is a poorly documented characteristic of cerebral
      aneurysms which may provide insight into adaptive aneurysmal growth, aneurysm
      rupture risk and response to endovascular treatment. The distribution of aneurysm
      wall thickness, as observed by intraoperative video microscopy, is described.
      METHODS: 54 unruptured saccular cerebral aneurysms were selected based on the
      availability of intraoperative video obtained from patients undergoing
      microsurgical clipping. Aneurysms were assessed for the distribution of wall
      thickness based on color translucence and quantitation of pixel values at
      superthin translucent, intermediate and thick regions of the dome. The data were
      analyzed with respect to aneurysm morphology, location and associated demographic
      factors. RESULTS: The mean proportions of tissue characteristic among all domes
      analyzed were found to be 27% superthin, 65% intermediate, and 8% thick. Smaller
      aneurysms having a maximal dimension Dmax <7 mm had a higher proportion of
      superthin tissue (p=0.003) and lower thick tissue (p=0.001) content. Female
      gender was associated with a significantly higher proportion of superthin tissue
      at the aneurysm dome (p=0.038), with no statistical dependence seen with patient
      age, smoking status or anatomical location. CONCLUSION: The dome of unruptured
      aneurysms is a highly heterogeneous region with areas of variable thickness that
      appear to be intimately related to the process of aneurysm development. This
      inconstant property affects wall tensile stress, may play a role in aneurysm
      pathogenesis and focal rupture, and should be incorporated into future analyses
      of aneurysm rupture risk and mechanics.

PMID- 22387725
TI  - Rapid genotyping of APOA5 -1131T>C polymorphism using high resolution melting
      analysis with unlabeled probes.
AB  - The APOA5 -1131 T/C polymorphism (rs662799) exhibits a very strong association
      with elevated TG levels in different racial groups. High resolution melting (HRM)
      analysis with the use of unlabeled probes has shown to be a convenient and
      reliable tool to genotyping, but not yet been used for detecting rs662799
      polymorphism. We applied the unlabeled probe HRM analysis and direct DNA
      sequencing to assay the -1131T>C SNP in 130 cases DNA samples blindly. This HRM
      analysis can be completed in <3 min for each sample. The two melting peaks were
      displayed at 66.1+/-0.4 degrees C for CC homozygote and 68.7+/-0.2 degrees C for
      TT homozygote; TC heterozygote showed the both melting peaks. The genotyping
      results by HRM method were completely concordant with direct DNA sequencing. The
      distribution of CC, TC, and TT genotypes for the -1131T>C SNP was 9.2, 49.2, and
      41.5%, respectively. This assay was sensitive enough to detect C allele down to
      20% and 10% for T allele. The limit of detection for C and T allele was 6.2 and
      2.5 ng/MUL DNA, respectively. The developed unlabeled probe HRM method provides
      an alternative mean to detect ApoA5 -1131T>C SNP rapidly and accurately.

PMID- 22387726
TI  - Disturbed ratio of renal 20-HETE/EETs is involved in androgen-induced
      hypertension in cytochrome P450 4F2 transgenic mice.
AB  - We have previously established a cytochrome P450 4F2 (CYP4F2) transgenic mouse
      model. The present study elucidated the molecular foundation of hypertension by
      androgen-induction in this model. The renal expression of CYP4F2 in transgenic
      mice was highly expressed and strongly induced with 5alpha-dihydrotestosterone
      (DHT) treatment determined by Western blot. DHT also increased the renal
      arachidonic acid omega-hydroxylation and urinary 20-hydroxyeicosatetraenoic acid
      (20-HETE) excretion (P<0.01), and furthermore elevated the systolic blood
      pressure by 10 and 22 mm Hg (P<0.05) in female and castrated male transgenic
      mice, respectively. HET0016 completely eliminated the androgen-induced effects
      (P<0.01). Endogenous Cyp4a omega-hydroxylases, evaluated by real-time
      quantitative PCR, were significantly suppressed in transgenic mice (P<0.05).
      Importantly, transgenic mice with increased 20-HETE showed decreased
      epoxyeicosatrienoic acids (EETs) and increased dihydroxyeicosatetraenoic acids
      determined by liquid chromatography-tandem mass spectrometry, contributing to
      significantly raised ratio of 20-HETE/EETs in the urine and kidney homogenate
      (P<0.01). These data demonstrate that the androgen aggravated hypertension
      possibly through an altered ratio of 20-HETE/EETs in CYP4F2 transgenic mice.

PMID- 22387727
TI  - Renin-angiotensin system genes polymorphism in Egyptians with premature coronary
      artery disease.
AB  - Genetics polymorphism of the renin-angiotensin system (RAS) affects the
      pathogenesis of atherosclerosis and associated with coronary artery disease
      (CAD). We aimed to investigate the association between the RAS genes and
      premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late
      onset CAD and 119 controls were included in the study. Angiotensin converting
      enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT)
      genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found
      that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86
      respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides
      and LDL cholesterol were independent risk factors for the development of PCAD. We
      conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the
      susceptibility of an individual to have PCAD. The coexistence of CAD risk factors
      with these risky RAS genotypes may lead to the development of PCAD in Egyptian
      patients.

PMID- 22387728
TI  - EULAR recommendations for terminology and research in individuals at risk of
      rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid
      Arthritis.
AB  - The Study Group for Risk Factors for Rheumatoid Arthritis was established by the
      EULAR Standing Committee on Investigative Rheumatology to facilitate research
      into the preclinical and earliest clinically apparent phases of rheumatoid
      arthritis (RA). This report describes the recommendation for terminology to be
      used to define specific subgroups during different phases of disease, and defines
      the priorities for research in this area. Terminology was discussed by way of a
      three-stage structured process: A provisional list of descriptors for each of the
      possible phases preceding the diagnosis of RA were circulated to members of the
      study group for review and feedback. Anonymised comments from the members on this
      list were fed back to participants before a 2-day meeting. 18 participants met to
      discuss these data, agree terminologies and prioritise important research
      questions. The study group recommended that, in prospective studies, individuals
      without RA are described as having: genetic risk factors for RA; environmental
      risk factors for RA; systemic autoimmunity associated with RA; symptoms without
      clinical arthritis; unclassified arthritis; which may be used in a combinatorial
      manner. It was recommended that the prefix 'pre-RA with:' could be used before
      any/any combination of the five points above but only to describe retrospectively
      a phase that an individual had progressed through once it was known that they
      have developed RA. An approach to dating disease onset was recommended. In
      addition, important areas for research were proposed, including research of other
      tissues in which an adaptive immune response may be initiated, and the
      identification of additional risk factors and biomarkers for the development of
      RA, its progression and the development of extra-articular features. These
      recommendations provide guidance on approaches to describe phases before the
      development of RA that will facilitate communication between researchers and
      comparisons between studies. A number of research questions have been defined,
      requiring new cohorts to be established and new techniques to be developed to
      image and collect material from different sites.

PMID- 22387729
TI  - Dual energy CT in gout: a prospective validation study.
AB  - OBJECTIVE: The authors prospectively determined: (1) the specificity and
      sensitivity of dual energy CT (DECT) for gout; and (2) the interobserver and
      intraobserver reproducibility for DECT urate volume measurements. METHODS: Forty
      crystal-proven gout patients (17 tophaceous) and 40 controls with other arthritic
      conditions prospectively underwent DECT scans of all peripheral joints using a
      gout protocol that color-codes the composition of tissues. A blinded radiologist
      identified urate deposition to calculate specificity and sensitivity of DECT for
      gout. Inter-rater volumetric reproducibility was determined by two independent
      radiologists on 40 index tophi from the 17 tophaceous gout patients using
      automated software. RESULTS: The mean age of the 40 gout patients was 62 years,
      the mean gout duration was 13 years and 87% had a history of urate-lowering
      therapy (ULT). The specificity and sensitivity of DECT for gout were 0.93 (95%
      CI, 0.80 to 0.98) and 0.78 (0.62 to 0.89), respectively. When the authors
      excluded three gout cases with unreadable or incomplete scans, the sensitivity
      was 0.84 (95% CI, 0.68 to 0.94). The urate volumes of 40 index tophi ranged from
      0.06 cm(3) to 18.74 cm(3) with a mean of 2.45 cm(3). Interobserver and
      intraobserver intraclass correlation coefficients for DECT volume measurements
      were 1.00 (95% CI, 1.00 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) with
      corresponding bias estimates (SD) of 0.01 (0.00) cm(3) and 0.01 (0.03) cm(3).
      CONCLUSIONS: These prospective data indicate high reproducibility of DECT urate
      volume measures. The specificity was high, but sensitivity was more moderate,
      potentially due to frequent ULT use in our patients.

PMID- 22387730
TI  - The effects of statins on osteoarthritis structural progression: another glimpse
      of the Holy Grail?

PMID- 22387732
TI  - One-pot synthesis of CdS and Ni-doped CdS hollow spheres with enhanced
      photocatalytic activity and durability.
AB  - CdS and Ni-doped CdS hollow spheres were synthesized via a simple template-free
      one-pot method. The products were characterized by X-ray powder diffraction,
      scanning electron microscopy, transmission electron microscopy, high-resolution
      transmission electron microscopy, energy-dispersive spectroscopy analysis, X-ray
      photoelectron spectroscopy, and UV-vis absorption spectroscopy. The formation
      mechanism for the Ni-doped CdS hollow spheres was discussed. The prepared CdS and
      Ni-doped CdS hollow spheres showed the superior photocatalytic activity for the
      degradation of RhB under visible light (lambda > 420 nm) irradiation, and 1.2 mol
      % Ni-doped CdS hollow spheres were found to be highly efficient for organic
      pollutants RhB and phenol removal. Moreover, this catalyst showed improved
      stability, and the activity did not decrease significantly after four recycles.
      The unique hollow spheres structure may favor the harvesting of exciting light
      due to multiple scattering within the interior space, and the doping of Ni(2+)
      may facilitate the generation of electrons and holes pairs and inhibit their
      recombination rate by act as a temporary trapping sites of photoinduced
      electrons.

PMID- 22387731
TI  - Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A
      is involved in lead-induced deficits in learning and memory in young rats.
AB  - Serine/threonine protein phosphatases regulate several key cellular events in the
      brain, including learning and memory. These enzymes, when over-activated, are
      known to function as a constraint on learning and memory. We investigated whether
      these phosphatases are implicated in lead (Pb)-induced deficits in learning and
      memory. Wistar rat pups were exposed to 0.2% Pb-acetate via their dams' drinking
      water from postnatal day (PND) 1-21 and directly in drinking water until PND 30.
      Pb levels in blood, brain and hippocampus were measured and expression of PP1,
      PP2A, PP2B and PP5 in hippocampus was analyzed. Total phosphatase activity, and
      PP1 and PP2A activities were determined. Tau phosphorylation at various epitopes
      was determined by Western blot. Spatial learning and memory was determined by
      Morris water maze test. Pb exposure significantly increased levels of Pb in
      blood, brain and hippocampus, reduced the number of synapses in hippocampus and
      impaired learning and long-term memory (LTM). Short-term memory (STM) was only
      affected in rats at PND21. Pb exposure increased the expression and activity of
      PP1 and decreased phosphorylation of tau at threonine-231 in hippocampus at both
      PND21 and PND30. Pb-induced phosphorylation of tau at serine-199/202 (AT8)
      paralleled with PP2A activity; at PND21 PP2A activity increased and AT8
      phosphorylation decreased; at PND30 PP2A activity decreased and AT8
      phosphorylation increased. Increased PP1 activity in hippocampus by Pb is
      associated with learning and LTM impairment, whereas, increased PP2A activity is
      associated with STM impairment. These findings suggest the overactivation of PP1
      and PP2A, together with changes in tau phosphorylation, as a potential mechanism
      of lead-induced deficits in learning and memory.

PMID- 22387734
TI  - Is there an optimal age for recovery from motor cortex lesions? II. behavioural
      and anatomical consequences of unilateral motor cortex lesions in perinatal,
      infant, and adult rats.
AB  - PURPOSE: The purpose of this study was to compare the behavioural and anatomical
      effects of unilateral motor cortex ablation in neonatal, infant, and adult rats.
      METHODS: Rats were given unilateral lesions of the motor cortex on the day of
      birth (P1), at ten days of age (P10), or in adulthood. They were trained on
      several motor tasks (skilled forelimb reaching, beam traversing, tongue
      extension), general motor activity, and a test of spatial learning (Morris water
      task). RESULTS: Although all lesion groups were equally impaired at skilled
      reaching with the forelimb contralateral to the lesion, rats with P1 lesions also
      were impaired at traversing a narrow beam and at learning the Morris task. Gross
      anatomical analyses revealed that the P1 rats had smaller brains than the other
      groups, a result that may account for the larger behavioural deficits in the P1
      group. Analysis of Golgi-Cox stained neurons showed that relative to control
      groups, all lesion groups showed an increase in dendritic length in the basilar
      dendrites of layer III pyramidal cells and, paradoxically a decrease in length of
      the apical dendrites of the same cells. CONCLUSIONS: The bilateral alterations in
      dendritic organization following the motor cortex lesions suggest that there has
      been a bilateral reor-ganization of intrinsic cortical connectivity following
      motor cortex lesions at any age. These alterations in connectivity are likely not
      identical in the young and adult animals, however, because relative to controls,
      both the young operated groups, but not the adult group, showed a bilat-eral drop
      in spine density in the basilar dendrites of layer V pyramidal cells. These
      findings are discussed with respect to the idea that there may be critical ages
      in development in which animals can use anatomical modifications to compensate
      for deficits produced by cortical injury.

PMID- 22387735
TI  - Neuronal nitric oxide synthase inhibitor has a neuroprotective effect in a rat
      model of brain injury.
AB  - PURPOSE: The aim of the present study was to assess the effects of neuronal
      nitric oxide synthase (NOS I) inhibitors and a combination of NOS I and NOS II
      inhibitors on lesion volume after experimental brain injury. METHODS: Cold lesion
      of the brain was induced by application of a precooled (.... 78  degrees C)
      copper cylinder to the intact dura of the rat for 6 s. Brains were removed 24 h
      after the injury and lesion volume determined using the triphenyltetrazolium
      chloride method. RESULTS: The specific NOS I inhibitor 3-bromo-7-nitroindazole
      (Br-7-NI) reduced lesion volume significantly by 21 % compared with the vehicle
      control. In contrast, 7-nitroindazole had no effect on lesion volume. When
      aminoguanidine, a specific NOS II inhibitor, was adminis-tered after Br-7-NI,
      lesion volume was significantly reduced but not significantly more than with
      either compound alone. CONCLUSION: Brain injury after cold lesion is partly
      mediated by NOS I activity and can be attenuated successfully with Br-7-NI, while
      coin-hibition of NOS II does not improve the outcome significantly.

PMID- 22387736
TI  - Training ameliorates deficits in visual detection and orienting following lesions
      of primary visual cortex sustained in adulthood and in infancy.
AB  - PURPOSE: Damage of primary visual cortex in adult humans, monkeys and cats
      severely disrupts vision by disconnecting much of the cogni-tive processing
      machinery of extrastriate cortex from its source of visual signals in the retina.
      Equivalent lesions sustained early in life result in partial sparing of visual
      processing functions and evidence from the mature brain suggests that systematic
      training procedures can ameliorate the impact of remaining deficits. The purpose
      of the present work was to use two reflex-based, visual detection and orienting
      tasks to test for the therapeutic effects of reha-bilitative training in cats
      that sustained lesions of primary cortical areas 17 & 18 in adulthood, and to
      test whether similar training is of benefit to cats that incurred equivalent
      lesions at one month-of-age (P28) or shortly after birth (P1). METHODS: Cats were
      trained to attend to static visual and auditory cynosures and tested on their
      ability to disengage the cynosure and orient towards a target presented in the
      periphery of the testing arena. Targets were: 1) a high contrast, dark, moved
      rod; 2) an illuminated static light-emitting diode (LED); and 3) a broad band,
      white noise, sound stimulus. RESULTS: On Task 1, cats with lesions of areas 17 &
      18 sustained in adulthood are markedly impaired whereas cats that sustained
      lesions in infancy exhibit partial sparing of the visual operations underlying
      this task. With training, the performance of all cats improved. On Task 2,
      performance by the adult-lesion and the P1-groups were markedly impaired, whereas
      the P28-group exhibited partial sparing. On Task 3, per-formance by all groups
      was uniformly high. No detectable benefits of training were identified on tasks 2
      and 3. CONCLUSIONS: Overall, the results show that cats incur definite benefits
      of training following visual cortex lesions regardless of whether the lesions
      were sustained early in life or later, but the benefits are limited to specific
      types of visual stimuli.

PMID- 22387737
TI  - Stroke-blind for colors, faces and locations: Partial recovery after three years.
AB  - Purpose. To study and follow-up achromatopsia, prosopagnosia, and
      topographagnosia in a patient who suffered a bilateral stroke of the posterior
      cerebral arteries. Methods. Ophthalmological, neuropsychological and
      neuroradiological examinations were conducted over a span of 3 years to assess
      the amount of brain damage and look for signs of functional recovery. Results.
      After the onset of achromatopsia, perception of the color green re-appeared
      first, followed by red, yellow, and brown. Blue which had appeared entirely black
      was last to return. While reading and color naming have largely recovered, color
      discrimination after three years remains poor especially in dim lighting.
      Similarly, with prosopagnosia, while the patient has learn to identify people
      (including photographs) by individual features, his ability to perceive and
      recognize faces and facial expressions holistically remains severely impaired.
      Recognition of streets, houses, and topographical layouts also continues to be
      affected, while the perception of speed and distance has somewhat improved.
      Perimetry further suggests a mild improvement of the superior hemianopia in his
      visual fields. Conclusions. Although major deficits in color, face and place
      perception remain, some functions impaired by the stroke have returned par
      alleling a partial recovery from the brain lesion as demonstrated by NMR.

PMID- 22387738
TI  - Long-term TGFa2 protein expression in heterotopic cortical grafts located in the
      rat striatum.
AB  - PURPOSE: Transforming growth factor beta 2 (TGFa2) is a multifunctional cytokine
      thought to play a crucial role in neuronal growth, differ-entiation and survival.
      In the cortex of adult rats, TGFa2 is constitutively expressed in a subset of
      neurons and astrocytes. In the present study we analyzed whether TGFa2 is also
      present in intrastriatal transplants of cortical anlage. In addition we
      investigated the temporo-spatial expression pattern of TGF2 in athe surrounding
      host striatum. METHODS: Cortical primordia of rat fetuses (E14) were
      stereotactically grafted into the rostral striatum of adult recipient rats.
      Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year,
      respectively, followed by morphological and immunohistochemical analysis.
      RESULTS: From week 2 on, TGFa 2-immunoreactivity (IR) was detectable in
      transplanted neurons. Within the graft, GFAP-IR was already present one week
      after transplantation, whereas TGFa2-immunostained astrocytes were first seen
      after 2 weeks. One year after transplanta-tion, TGFa2 positive neurons and
      astrocytes were still present. In the host striatum and at the graft-host
      interface an increase of TGFa2-immu-noreactive astrocytes first occured after one
      week both in grafted animals and in sham-operated (lesioning without grafting)
      rats. CONCLUSIONS: Our data suggest that at least a subpopulation of transplanted
      neurons develops a phenotype as cortical neurons in situ with respect to TGFa2
      expression. Upregulation of astrocytic TGFa2 expression within the graft,
      however, is due to the trauma imposed by the transplantation procedure rather
      than an intrinsic differentiation program of co-grafted astrocytes.

PMID- 22387739
TI  - Target-dependent axonal sprouting following vagal-hypoglossal nerve anastomosis
      in cats.
AB  - PURPOSE: To investigate the relationships between the axonal sprouting and target
      neurotization by central neurons after nerve heteroconnection. METHODS:
      Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in
      adult cats. Following 3-315 days postoperation (dpo), quantitative analyses and
      ultrastructural changes in the proximal portion of the vagal-hypoglossal
      heteroconnected nerve as well as the time course of neuronal regeneration were
      studied. Along with this, horseradish peroxidase (HRP) retrograde tracing
      technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and
      nucleus ambiguus (NA) to ascertain if target neurotization was established.
      RESULTS: The contralateral (left) intact vagus nerve proximal to the level of
      ansa cervicalis showed an average of 33 +/- 1 myelinated and 74 +/- 4
      unmyelinated axons in 727 MUm2 sectional area of the nerve. In the
      heteroconnected nerve at the corresponding level just proximal to the anastomosis
      site, there was a marked increase in the number of small axons sprouting from the
      unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal
      sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained
      until the late regeneration stage at 315 dpo when compared with the contralateral
      nerve serving as a control. The mean number of myelinated axons per area unit
      (727 MUm2) was reduced to 18 at 3 dpo but was immediately restored to the normal
      range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was
      first detected at 22 dpo and was progressively increased peaking by about 67 dpo.
      CONCLUSIONS: We conclude that compared with the unmyelinated axons, the
      myelinated axons may acquire a superior interaction with the new target.
      Furthermore, the postoperative neurotization of tongue muscles may initiate and
      facilitate the retraction of the redundant axonal sprouts.

PMID- 22387740
TI  - Changes in BDNF and neurotrophin receptor expression in degenerating and
      regenerating rat retinal ganglion cells.
AB  - PURPOSE: Exogenously applied BDNF has been shown to rescue rat retinal ganglion
      cells (RGCs) from axotomy-induced apoptotic death, presumably via activation of
      its high affinity receptor TrkB. Since both TrkB and BDNF are endogenously
      expressed in RGCs, auto- or para-crine neurotrophic loops in the retina may be
      involved. In the present study, we investigated whether expression levels of
      BDNF, TrkA, TrkB, TrkC and p75 protein in RGCs are specifically regulated
      following axonal lesion and during regeneration of optic fibres in the adult rat.
      METHODS: By double labelling retinal cryosections with Fluorogold and respective
      antibodies we determined the percentage of RGCs expressing the above-mentioned
      markers. In addition, mRNA levels of BDNF and TrkB were measured using
      quantitative RT-PCR. RESULTS: Compared to controls the number of BDNF-positive
      RGCs increased twofold 2 days after axotomy and the percentage of RGCs expressing
      TrkB was elevated by 50 %. Correspondingly, mRNA levels of BDNF increased about
      twofold 2 days after axotomy. During regen-eration, the percentage of BDNF
      immunoreactive RGCs was further elevated compared to axotomy alone. The number of
      TrkA-positive RGCs doubled after axotomy, whereas no significant change in TrkC
      expression was observed. P75 expression was not detected in adult rat RGCs.
      CONCLUSION: Our results suggest that intrinsic rescue mechanisms may contribute
      to short term neuronal survival and axonal regeneration of RGCs after axonal
      lesions.

PMID- 22387741
TI  - Diethyldithiocarbamate (DEDC) impairs neuronal recovery following sciatic nerve
      injury in rats.
AB  - PURPOSE: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is
      metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC
      has received considerable attention because of its clinical applications and
      potential role in mediating both the toxic and therapeutic actions of disulfiram
      which is frequently used for alcohol aversion therapy. DEDC is known for its
      multiplicity of action that exerts both pro- and antioxidant effects. In rodents
      DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The
      purpose of this study was to examine the effect of DEDC on neurological recovery
      following sciatic nerve crush injury (SNCI) in rats. METHODS: Adult female Wistar
      rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals
      were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg
      body weight 1 hr before SNCI and then once daily for 60 days. The animals were
      observed for sciatic functional index (walking deficit), electrophysiological and
      histological changes. Vitamin E level was measured to deter-mine antioxidant
      status of sciatic nerve. RESULTS: Crush injury to the sciatic nerve resulted in a
      significant impairment of functional response which gradually recovered over a
      period of 22 days. Treatment of animals with DEDC caused a significant delay in
      functional recovery which was accompanied by poor histo-logical and
      electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a
      significant decrease in vitamin E levels in both injured and uninjured sciatic
      nerves. CONCLUSIONS: Our results demonstrate that exposure to DEDC adversely
      affects recovery from peripheral nerve injury. The delay may to some extent be
      attributed to DEDC induced oxidative stress.

PMID- 22387742
TI  - Abstracts of the 15 th Annual Meeting of the Japanese Society for Neural Growth,
      Regeneration and Transplantation.

PMID- 22387743
TI  - Abstracts of the 5th international neurotrauma symposium.

PMID- 22387744
TI  - Surfing the data tsunami, a bioinformatic dissection of the proangiogenic
      monocyte.
AB  - In this review we compare expression studies on monocyte subsets as an example to
      show the integrated possibilities of molecular databases and bioinformatic
      analysis tools. Monocytes have been recognized as cells with great plasticity and
      differentiation potential that play a pivotal role in revascularization
      processes, i.e. angiogenesis and arteriogenesis. To gain more insight in the
      relevant developmental programs, we compared the full-genome mRNA expression
      profiles of several distinct human monocyte subpopulations previously identified
      based on surface marker expression. These included classical and non-classical,
      M1 and M2 macrophages, circulating angiogenic cells (CAC), and non-monocyte
      derived endothelial colony-forming cells (ECFC). Their transcriptional profiles
      revealed distinct and overlapping gene expression signatures and pathways
      reminiscent of utilization of transcription factors driving polarization into the
      different monocytic phenotypes. Hierarchical cluster analysis revealed that CAC
      are most related to M2 macrophages and unstimulated macrophages, and to a lesser
      extent to classical monocytes, and are quite distinct from M1 macrophages and
      ECFC. Analysis of the promoter region of CAC-expressed genes suggests that in
      particular the ETS family of transcription factors is important in CAC
      development. These analyses show the power of combining multiple datasets with
      existing databases on biological knowledge, to interpret full genome expression
      data.

PMID- 22387745
TI  - Development of pluripotent stem cells for vascular therapy.
AB  - Peripheral arterial disease (PAD) is characterized by reduced limb blood flow due
      to arterial obstruction. Current treatment includes surgical or endovascular
      procedures, the failure of which may result in amputation of the affected limb.
      An emerging therapeutic approach is cell therapy to enhance angiogenesis and
      tissue survival. Small clinical trials of adult progenitor cell therapies have
      generated promising results, although large randomized clinical trials using well
      defined cells have not been performed. Intriguing pre-clinical studies have been
      performed using vascular cells derived from human embryonic stem cells (hESC) or
      human induced pluripotent stem cells (hiPSCs). In particular, hiPSC-derived
      vascular cells may be a superior approach for vascular regeneration. The
      regulatory roadmap to the clinic will be arduous, but achievable with further
      understanding of the reprogramming and differentiation processes; with meticulous
      attention to quality control; and perseverance.

PMID- 22387746
TI  - Predictive modeling of chemical hazard by integrating numerical descriptors of
      chemical structures and short-term toxicity assay data.
AB  - Quantitative structure-activity relationship (QSAR) models are widely used for in
      silico prediction of in vivo toxicity of drug candidates or environmental
      chemicals, adding value to candidate selection in drug development or in a search
      for less hazardous and more sustainable alternatives for chemicals in commerce.
      The development of traditional QSAR models is enabled by numerical descriptors
      representing the inherent chemical properties that can be easily defined for any
      number of molecules; however, traditional QSAR models often have limited
      predictive power due to the lack of data and complexity of in vivo endpoints.
      Although it has been indeed difficult to obtain experimentally derived toxicity
      data on a large number of chemicals in the past, the results of quantitative in
      vitro screening of thousands of environmental chemicals in hundreds of
      experimental systems are now available and continue to accumulate. In addition,
      publicly accessible toxicogenomics data collected on hundreds of chemicals
      provide another dimension of molecular information that is potentially useful for
      predictive toxicity modeling. These new characteristics of molecular bioactivity
      arising from short-term biological assays, i.e., in vitro screening and/or in
      vivo toxicogenomics data can now be exploited in combination with chemical
      structural information to generate hybrid QSAR-like quantitative models to
      predict human toxicity and carcinogenicity. Using several case studies, we
      illustrate the benefits of a hybrid modeling approach, namely improvements in the
      accuracy of models, enhanced interpretation of the most predictive features, and
      expanded applicability domain for wider chemical space coverage.

PMID- 22387747
TI  - Mitochondrial dysfunction induced by sertraline, an antidepressant agent.
AB  - Sertraline, a selective serotonin reuptake inhibitor, has been used for the
      treatment of depression. Although it is generally considered safe, cases of
      sertraline-associated liver injury have been documented; however, the possible
      mechanism of sertraline-associated hepatotoxicity is entirely unknown. Here, we
      report that mitochondrial impairment may play an important role in liver injury
      induced by sertraline. In mitochondria isolated from rat liver, sertraline
      uncoupled mitochondrial oxidative phosphorylation and inhibited the activities of
      oxidative phosphorylation complexes I and V. Additionally, sertraline induced
      Ca(2+)-mediated mitochondrial permeability transition (MPT), and the induction
      was prevented by bongkrekic acid (BA), a specific MPT inhibitor targeting adenine
      nucleotide translocator (ANT), implying that the MPT induction is mediated by
      ANT. In freshly isolated rat primary hepatocytes, sertraline rapidly depleted
      cellular adenosine triphosphate (ATP) and subsequently induced lactate
      dehydrogenase leakage; both were attenuated by BA. Our results, including ATP
      depletion, induction of MPT, inhibition of mitochondrial respiration complexes,
      and uncoupling oxidative phosphorylation, indicate that sertraline-associated
      liver toxicity is possibly via mitochondrial dysfunction.

PMID- 22387748
TI  - Poly(ADP-ribose) polymerase-1 inhibition by arsenite promotes the survival of
      cells with unrepaired DNA lesions induced by UV exposure.
AB  - Human arsenic exposure is associated with increased risk of skin cancer, and
      arsenite greatly enhances ultraviolet (UV)-induced skin tumors in a mouse model
      of carcinogenesis. Inhibition of DNA repair is one proposed mechanism for the
      observed cocarcinogenicity. We have previously demonstrated that low
      concentrations of arsenite inhibit poly(ADP-ribose) polymerase (PARP)-1, thus
      interfering with DNA repair process triggered by UV radiation. Because
      overactivation of PARP-1 often leads to apoptotic cell death, and unrepaired DNA
      lesions promote genomic instability and carcinogenesis, we hypothesized that
      inhibition of PARP-1 by arsenic may promote the survival of potentially
      "initiated carcinogenic cells," i.e., cells with unrepaired DNA lesions. In the
      present study, we tested this hypothesis on UV-challenged HaCat cells. Cells were
      pretreated with 2MUM arsenite for 24 h before UV exposure. Outcome parameters
      included apoptotic death rate, PARP-1 activation, apoptotic molecules, and
      retention of DNA lesions. UV exposure induced PARP-1 activation and associated
      poly(ADP-ribose) production, apoptosis-inducing factor release, cytochrome C
      release, and caspases activation, which led to apoptotic death in HaCat cells.
      Pretreatment with 2MUM arsenite significantly inhibited UV-induced cell death as
      well as the associated molecular events. Notably, knockdown of PARP-1 with small
      interfering RNA completely abolished the antagonism of arsenite. Furthermore,
      arsenite pretreatment led to long-term retention of UV-induced cyclobutane
      pyrimidine dimers. Together, these results suggest that low concentration of
      arsenite reduces UV-induced apoptosis via inhibiting PARP-1, thus promoting the
      survival of cells with unrepaired DNA lesions, which may be an important
      mechanism underlying arsenic cocarcinogenic action.

PMID- 22387749
TI  - Effects of chronic exposure to an environmentally relevant mixture of brominated
      flame retardants on the reproductive and thyroid system in adult male rats.
AB  - Brominated flame retardants (BFRs) are incorporated into a wide variety of
      consumer products, are readily released into home and work environments, and are
      present in house dust. Studies using animal models have revealed that exposure to
      polybrominated diphenyl ethers (PBDEs) may impair adult male reproductive
      function and thyroid hormone physiology. Such studies have generally
      characterized the outcome of acute or chronic exposure to a single BFR technical
      mixture or congener but not the impact of environmentally relevant BFR mixtures.
      We tested whether exposure to the BFRs found in house dust would have an adverse
      impact on the adult male rat reproductive system and thyroid function. Adult male
      Sprague Dawley rats were exposed to a complex BFR mixture composed of three
      commercial brominated diphenyl ethers (52.1% DE-71, 0.4% DE-79, and 44.2% decaBDE
      209) and hexabromocyclododecane (3.3%), formulated to mimic the relative congener
      levels in house dust. BFRs were delivered in the diet at target doses of 0, 0.02,
      0.2, 2, or 20 mg/kg/day for 70 days. Compared with controls, males exposed to the
      highest dose of BFRs displayed a significant increase in the weights of the
      kidneys and liver, which was accompanied by induction of CYP1A and CYP2B P450
      hepatic drug-metabolizing enzymes. BFR exposure did not affect reproductive organ
      weights, serum testosterone levels, testicular function, or sperm DNA integrity.
      The highest dose caused thyroid toxicity as indicated by decreased serum
      thyroxine (T4) and hypertrophy of the thyroid gland epithelium. At lower doses,
      the thickness of the thyroid gland epithelium was reduced, but no changes in
      hormone levels (T4 and thyroid-stimulating hormone) were observed. Thus, exposure
      to BFRs affected liver and thyroid physiology but not male reproductive
      parameters.

PMID- 22387750
TI  - Prostaglandin synthases influence thyroid follicular cell proliferation but not
      carcinogenesis in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.
AB  - To clarify roles of prostaglandin synthases in rat thyroid follicular
      carcinogenesis, effects of an antithyroid agent, sulfadimethoxine (SDM), and two
      prostaglandin H synthase (COX) inhibitors, indomethacin and nimesulide, on
      prostaglandin synthase expression, follicular cell proliferation, and tumor
      induction in thyroids of rats with or without N-bis(2-hydroxypropyl)nitrosamine
      (DHPN) initiation were examined. In experiment 1, F344 male rats were allowed
      free access to drinking water containing SDM (0.1%), SDM + indomethacin (0.0025%
      in diet), or SDM + nimesulide (0.04% in diet) for 4 weeks. Both COX inhibitors
      suppressed goitrogenic activity of SDM, but they did not significantly affect
      microsomal prostaglandin E synthase-2 (mPGES-2) expression levels enhanced by
      SDM. In experiment 2, all rats received an injection of DHPN (2800 mg/kg body
      weight), and starting 1 week later, they were treated as in experiment 1 for 4 or
      10 weeks. Cell proliferation was suppressed or showed a tendency for suppression
      by the COX inhibitors in the follicular preneoplastic/neoplastic lesions and
      surrounding parenchyma, and this was obviously thyroid stimulating hormone
      independent at least at week 4. However, neither of the COX inhibitors altered
      the incidence or multiplicity of preneoplastic/neoplastic lesions.
      Immunohistochemistry revealed significant reduction and elevation of COX-2 and
      mPGES-2 expression, respectively, in the lesions, but these were also not changed
      by the COX inhibitors. These results suggest that COX-2 and PGES, and in turn
      PGE(2), might play important roles in follicular cell proliferation but do not
      affect tumor induction in this rat thyroid carcinogenesis model. Further studies
      are needed to clarify the significance of the reduction of COX-2 expression in
      preneoplastic/neoplastic lesions.

PMID- 22387751
TI  - Norrin: molecular and functional properties of an angiogenic and neuroprotective
      growth factor.
AB  - Norrin is a secreted signaling molecule with structural and functional
      characteristics of an autocrine and/or paracrine acting growth factor. In the
      eye, Norrin is constitutively expressed in Muller cells. Norrin specifically
      binds to Frizzled-4 receptors and activates the canonical Wnt/beta-catenin
      signaling pathway that is profoundly enhanced when Tspan12 is present at the
      Norrin/Frizzled-4 receptor complex. In the absence of Norrin or Frizzled-4,
      intraretinal capillaries are not formed during developmental angiogenesis. As a
      result there is considerable evidence that Norrin and Frizzled-4 are part of an
      essential signaling system that controls the formation of the retinal vasculature
      during eye development. Intriguingly, Norrin promotes vessel regrowth and induces
      the formation of intraretinal capillaries following oxygen-induced retinopathy in
      mice, an animal model of retinopathy of prematurity. Moreover, Norrin has
      pronounced neuroprotective properties on retinal ganglion cells (RGC) with the
      distinct potential to decrease the damaging effects of excitotoxic NMDA-induced
      RGC injury. The neuroprotective effects of Norrin similarly involve an activation
      of Wnt/beta-catenin signaling and the subsequent induction of neuroprotective
      growth factor synthesis in Muller cells, such as that of fibroblast growth factor
      2 (FGF2) or ciliary neurotrophic factor (CNTF). Overall, Norrin and the molecules
      involved in its signaling pathway appear to be promising targets to develop
      strategies that induce intraretinal vessel formation in patients suffering from
      ischemic retinopathies, or that increase RGC survival in glaucoma.

PMID- 22387752
TI  - Single sublethal dose of microcystin-LR is responsible for different alterations
      in biochemical, histological and physiological renal parameters.
AB  - Microcystins (MCYSTs) are very stable cyclic peptidic toxins produced by
      cyanobacteria. Their effects on hepatic tissue have been studied extensively, and
      they are considered to be a potent hepatotoxin. However, several effects of MCYST
      on other organs have also been described, but generally in studies using higher
      doses of MCYST. In the present work, we investigated the effect of a single
      sublethal dose of MCYST-LR (55 MUg/kg) in Wistar rats and analyzed different
      aspects that influenced renal physiology, including toxin accumulation,
      excretion, histological morphology, biochemical responses and oxidative damage in
      the kidney. After 24 h of exposure to MCYST-LR, it was possible to observe an
      increased glomerular filtration rate (6.28 +/- 1.56 vs 2.16 +/- 0.48 MUl/min per
      cm(2)) compared with the control group. Increase of interstitial space and
      collagen deposition corresponded to a fibrotic response to the increased
      production of reactive oxygen species. The observed decrease of Na(+)
      reabsorption was due to inhibition of the activity of both Na(+) pumps in
      proximal tubules cells. We suggested that this modulation is mediated by the
      effect of MCYST as a phosphatase protein inhibitor that maintains the sustained
      kinase-mediated regulatory phosphorylation of the ATPases. The observed
      alteration of Na(+) active transporters lead to damage of renal function, since
      are involved in regulation of water and solute reabsorption in proximal tubules.
      The results of this report reinforce the importance of understanding the
      molecular effects of a single sublethal dose of MCYST-LR, which, in this study,
      was responsible for macro-alterations found in the renal parenchyma and renal
      physiology in rats.

PMID- 22387753
TI  - Identifying predictors of an abnormal computed tomographic scan among patients
      with a head injury and a Glasgow Coma Scale of 15.
AB  - AIM: The aim of this study was to determine the proportions of patients with a
      head injury and a Glasgow Coma Scale of 15 with an abnormal computed tomographic
      (CT) head scan and to explore its predictors. METHODS: We conducted a
      retrospective study on adult patients with such injuries. Patients were risk
      stratified to undergo a head CT and subsequently discharged or admitted to a
      neurosurgical (NS) intensive care unit (ICU)/high-dependency (HD) NS or general
      ward (GW) and observation ward [Emergency Diagnostic and Therapeutic Centre
      (EDTC)]. The primary outcomes were proportions of abnormal CT results and NS
      interventions. The secondary outcomes included rates of disposition status, and
      the distribution and predictors of abnormal CT results. Data were analysed using
      descriptive statistics. We identified predictors of an abnormal head CT using
      logistic regression and reported their odds ratios (ORs) and 95% confidence
      intervals. RESULTS: We reviewed 2038 complete records. A total of 1088 scans were
      performed; 115 (10.6%) were abnormal. There were 962 (47.2%) discharges and 1076
      (52.8%) admissions; six (0.6%) required NS interventions and ICU/HD admission.
      The proportions of GW admissions (n=1070) were as follows: EDTC 78.0%; NS 18.0%;
      and medical 4.0%. The proportions of abnormal CT results among these disposition
      statuses were as follows: NS ICU/HD 6/6 (100%); EDTC 59/835 (7.1%); NS GW 47/188
      (25.0%); and medical GW 3/33 (9.1%). We identified three predictors, namely,
      vomiting [OR 2.23 (1.39-3.58)]; loss of consciousness [OR 1.56 (1.03-2.36)]; and
      amnesia [OR 2.08 (1.30-3.31)]. CONCLUSION: Abnormal CT and NS interventions were
      infrequent in patients with a head injury and a Glasgow Coma Scale of 15. We
      identified three predictors of abnormal head CTs.

PMID- 22387754
TI  - Chief complaints in medical emergencies:  do they relate to underlying disease
      and outcome? The Charite Emergency Medicine Study (CHARITEM).
AB  - OBJECTIVES: To evaluate the relationship between chief complaints and their
      underlying diseases and outcome in medical emergency departments (EDs). METHODS:
      All 34 333 patients who attended two of the EDs of the Charite Berlin over a 1
      year period were included in the analysis. Data were retrieved from the hospital
      information system. For study purposes, the chief complaint (chest pain,
      dyspnoea, abdominal pain, headache or 'none of these symptoms') was prospectively
      documented in an electronic file by the ED-physician. Documentation was
      mandatory. RESULTS: The majority of patients (66%) presented with 'none of these
      symptoms', 11.5% with chest pain, 11.1% with abdominal pain and 7.4% with
      dyspnoea. In total, 39.4% of all patients were admitted to the hospital. The
      leading diagnosis was acute coronary syndrome (50.7%) for chest pain in-patients
      and chronic obstructive pulmonary disease (16.5%) and heart failure (16.1%) for
      in-patients with dyspnoea. The causes of abdominal pain in in-patients were of
      diverse gastrointestinal origin (47.2%). In-hospital mortality of in-patients was
      4.7%. Patients with chest pain had significantly lower in-hospital mortality
      (0.9%) than patients with dyspnoea (9.4%) and abdominal pain (5.1%). CONCLUSION:
      The majority of emergency patients lack diagnosis-specific symptoms. Chief
      complaints help preselect patients but must not be mistaken as disease specific.
      Mortality largely differs depending on the chief complaint. In chest pain
      patients, standardized processes may be one factor that explains the low
      mortality in this group.

PMID- 22387757
TI  - Autonomic nervous system correlates to readiness state and negative outcome
      during visual discrimination tasks.
AB  - Decision-making in daily activities require different levels of mental load
      depending on both objective task requirements and self-perception of task
      constraints. Such factors elicit strain that could influence information
      processing, decision-making, and forthcoming performance. This experiment aimed
      at studying how task difficulty, errors and unfair feedback may impact strain.
      Participants were requested to compare two polygons and to decide as quickly and
      accurately as possible whether these were identical or different. Task difficulty
      depended upon the number of polygon sides (from 12 to 21 sides) and their degree
      of similarity (different by 1, 2 or 3 sides). Reaction time (RT) and response
      accuracy were the dependent variables as well as electrodermal activity (EDA) and
      Instantaneous Heart Rate (IHR). Physiological variables from the autonomic
      nervous system were expected to evolve as a function of strain. As expected, we
      found that RT increased along with task difficulty. Similarly, the amplitude of
      IHR responses was affected by task difficulty. We recorded bradycardia during the
      5s pre-stimulation period associated with correct responses, while wrong
      responses were associated with tachycardia. Bradycardia was thus a predictive
      index of performance related to the readiness to act when the participants
      focused on external cues. Processing identical polygons elicited longer
      electrodermal responses than those for different polygons. Indeed, the comparison
      of two different polygons ended as early as the difference was found. When
      similar, the participants were still looking for a difference and the issue was
      uncertain until the performance was displayed. Unfair information, i.e. wrong
      feedback associated with a good response, as well as response errors elicited
      larger and longer electrodermal responses. Autonomic nervous system activity was
      thus task-specific, and correlated to both cognitive and emotional processes.

PMID- 22387758
TI  - P3 response during short-term memory retrieval revisited by a spatio-temporal
      analysis.
AB  - The most reported event related potential (ERP) parameter during short-term
      memory retrieval has been P3 wave and the association has been built on the
      relation between P3 latency and reaction times. The aim of this study is to
      identify an ERP component that reflects the memory scanning process preceding the
      decision making stage which has been associated with the P3 peak. A
      spatiotemporal analysis was applied on the P3 and pre-P3 period of ERP responses
      obtained during the retrieval phase of the Sternberg paradigm with two memory
      load conditions (3 and 5 letters in the memory set). In the easy task condition
      with the fastest reaction times (positive probes of 3 letters condition), a
      single P3 was observed, whereas P3 was split into two peaks in responses to probe
      items of more demanding task conditions. The single P3 peak and the later
      components of the split P3 peaks displayed the typical P3 topography. On the
      other hand, the topographic mapping of the earlier peak of the split P3 wave and
      ascending part of the single P3 peak revealed a right parietal topography. The
      onset time of this earlier right lateralized topography was stable among all
      conditions but it persisted longer in the high memory load condition. We conclude
      that the right-lateralized positivity in the pre-P3 period reflects the memory
      scanning process followed by the P3 peak with midline parietal topography
      reflecting the decision making process.

PMID- 22387760
TI  - In silico identification of conserved intercoding sequences in Leishmania
      genomes: unraveling putative cis-regulatory elements.
AB  - In silico analyses of Leishmania spp. genome data are a powerful resource to
      improve the understanding of these pathogens' biology. Trypanosomatids such as
      Leishmania spp. have their protein-coding genes grouped in long polycistronic
      units of functionally unrelated genes. The control of gene expression happens by
      a variety of posttranscriptional mechanisms. The high degree of synteny among
      Leishmania species is accompanied by highly conserved coding sequences (CDS) and
      poorly conserved intercoding untranslated sequences. To identify the elements
      involved in the control of gene expression, we conducted an in silico
      investigation to find conserved intercoding sequences (CICS) in the genomes of L.
      major, L. infantum, and L. braziliensis. We used a combination of computational
      tools, such as Linux-Shell, PERL and R languages, BLAST, MSPcrunch, SSAKE, and
      Pred-A-Term algorithms to construct a pipeline which was able to: (i) search for
      conservation in target-regions, (ii) eliminate CICS redundancy and mask repeat
      elements, (iii) predict the mRNA's extremities, (iv) analyze the distribution of
      orthologous genes within the generated LeishCICS-clusters, (v) assign GO terms to
      the LeishCICS-clusters, and (vi) provide statistical support for the gene
      enrichment annotation. We associated the LeishCICS-cluster data, generated at the
      end of the pipeline, with the expression profile of L. donovani genes during
      promastigote-amastigote differentiation, as previously evaluated by others (GEO
      accession: GSE21936). A Pearson's correlation coefficient greater than 0.5 was
      observed for 730 LeishCICS-clusters containing from 2 to 17 genes. The designed
      computational pipeline is a useful tool and its application identified potential
      regulatory cis elements and putative regulons in Leishmania.

PMID- 22387759
TI  - Effect of human TGF-beta on the gene expression profile of Schistosoma mansoni
      adult worms.
AB  - Schistosoma mansoni is responsible for schistosomiasis, a parasitic disease that
      affects 200 million people worldwide. Molecular mechanisms of host-parasite
      interaction are complex and involve a crosstalk between host signals and parasite
      receptors. TGF-beta signaling pathway has been shown to play an important role in
      S. mansoni development and embryogenesis. In particular human (h) TGF-beta has
      been shown to bind to a S. mansoni receptor, transduce a signal that regulates
      the expression of a schistosome target gene. Here we describe 381 parasite genes
      whose expression levels are affected by in vitro treatment with hTGF-beta. Among
      these differentially expressed genes we highlight genes related to morphology,
      development and cell cycle that could be players of cytokine effects on the
      parasite. We confirm by qPCR the expression changes detected with microarrays for
      5 out of 7 selected genes. We also highlight a set of non-coding RNAs transcribed
      from the same loci of protein-coding genes that are differentially expressed upon
      hTGF-beta treatment. These datasets offer potential targets to be explored in
      order to understand the molecular mechanisms behind the possible role of hTGF
      beta effects on parasite biology.

PMID- 22387761
TI  - Cortical representation of medial axis structure.
AB  - The identity of an object is not only specified by its parts but also by the
      relations among the parts. Rearranging parts can produce a completely different
      object, in the same manner as rearranging the phonemes in "fur" can yield
      "rough." How does the visual system represent the relative positions of parts?
      Between-part relations can be characterized by specifying the relations between
      the medial axes (imaginary lines through the centers) of an object's parts. A
      functional magnetic resonance imaging multivoxel classification study tested
      whether the medial axis structure is represented in the human visual system
      independent of part identity and overall object orientation. Stimuli were line
      drawings of novel 3-part geometrical objects, which differed in the relations
      between their parts' medial axes (i.e., in their medial axis structures), the
      geons that composed each object, and the objects' orientations in plane and in
      depth. In regions of interest throughout visual cortex, a support vector machine
      classifier was trained to distinguish objects that shared either the same medial
      axis structures or the same orientations. By the level of V3, different medial
      axis structures were more accurately classified than different orientations,
      indicating a change in the representation of shape compared with earlier visual
      areas.

PMID- 22387805
TI  - Polycyclic aromatic hydrocarbons suppress meiosis in primordial germ cells via
      the AHR signaling pathway.
AB  - Numerous studies have demonstrated that polycyclic aromatic hydrocarbon (PAH)
      exposure during pregnancy is associated with negative reproductive consequences
      in adulthood, such as reduced sperm production and oocyte destruction in human
      and laboratory animals. However, the mechanism(s) underlying these
      epidemiological findings is still unclear, largely due to the lack of an in vitro
      model of gametogenesis. Here we established an in vitro model of gametogenesis
      through retinoic acid (RA)-induced differentiation of chicken primordial germ
      cells (PGCs) that progressed through meiosis to generate 55% of haploid cells.
      Using this system, we demonstrated that PAH exposure directly suppressed meiotic
      initiation and completion in chicken PGCs and promoted the apoptosis of PGCs,
      eventually leading to reduction of haploid cell formation by 66.9%. Furthermore,
      knockdown experiments suggested that AHR was essential for the adverse effects of
      PAH on PGC differentiation. Collectively, these findings offer novel insight into
      the dynamic mechanism by which PAH affects gametogenesis, suggesting that AHR
      dependent inhibition of meiosis might be the cause of reduced gamete production.
      This study also provides a novel model for direct examination of the molecular
      and genetic pathways of environmental toxicants on gametogenesis.

PMID- 22387806
TI  - Low-dose neonatal domoic acid causes persistent changes in behavioural and
      molecular indicators of stress response in rats.
AB  - Appropriate stress responses rely on a finely-tuned neuronal balance that must
      continually adapt to a frequently changing external environment. Alterations in
      this balance can result in susceptibility to a variety of stress-related
      disorders, as well as exacerbate already existing conditions. We have previously
      reported that rat pups injected with a very low dose (20 MUg/kg) of domoic acid
      during the second postnatal week of life display low-grade seizure behaviours
      when challenged with stressful tasks, and also exhibit a variety of structural
      and functional changes similar to those seen in temporal lobe epilepsy. The
      current study was designed to investigate markers of altered stress-response in
      this model. Following neonatal treatment, adult rats were tested in the elevated
      plus maze, as well as two water maze tasks, both of which involved a platform
      reversal challenge. Results indicated a modified behavioural stress/anxiety
      response, increased perseveration, and alterations in search strategy for all
      domoate-treated rats, as well as male-specific deficits in cognitive flexibility.
      In addition, 80% of treated males and 20% of treated females exhibited seizure
      behaviour. Western blot analysis revealed male-only increases in adrenergic
      receptor (alpha2a and alpha2c) and mineralocorticoid receptor expression, and
      subtle sex-specific changes in glucocorticoid receptor expression, but no
      differences in corticotropin-releasing factor receptors I/II, or dopamine D2
      receptor expression. A significant decrease in glucocorticoid:mineralocorticoid
      ratio was also noted. We conclude that early exposure to DOM alters central
      mechanisms underlying stress response, and that this model may be valuable for
      investigating the connection between stress and neurological disorders.

PMID- 22387809
TI  - Lack of neuromuscular origins of adaptation after a long-term stretching program.
AB  - CONTEXT: Static stretching is commonly used during the treatment and
      rehabilitation of orthopedic injuries to increase joint range of motion (ROM) and
      muscle flexibility. Understanding the physiological adaptations that occur in the
      neuromuscular system as a result of long-term stretching may provide insight into
      the mechanisms responsible for changes in flexibility. OBJECTIVE: To examine
      possible neurological origins and adaptations in the Ia-reflex pathway that allow
      for increases in flexibility in ankle ROM, by evaluating the reduction in the
      synaptic transmission of Ia afferents to the motoneuron pool. DESIGN: Repeated
      measures, case-controlled study. SETTING: Sports medicine research laboratory.
      PARTICIPANTS: 40 healthy volunteers with no history of cognitive impairment,
      neurological impairment, or lower extremity surgery or injury within the previous
      12 mo. INTERVENTION: Presynaptic and postsynaptic mechanisms were evaluated with
      a chronic stretching pro- tocol. Twenty subjects stretched 5 times a wk for 6 wk.
      All subjects were measured at baseline, 3 wk, and 6 wk. MAIN OUTCOME MEASURES:
      Ankle-dorsiflexion ROM, Hmax:Mmax, presynaptic inhibition, and disynaptic
      reciprocal inhibition. RESULTS: Only ROM had a significant interaction between
      group and time, whereas the other dependent variables did not show significant
      differences. The experimental group had significantly improved ROM from baseline
      to 3 wk (mean 6.2 +/- 0.9, P < .001), 3 wk to 6 wk (mean 5.0 +/- 0.8, P < .001),
      and baseline to 6 wk (mean 11.2 +/-0.9, P < .001). CONCLUSIONS: Ankle
      dorsiflexion increased by 42.25% after 6 wk of static stretching, but no
      significant neurological changes resulted at any point of the study, contrasting
      current literature. Significant neuromuscular origins of adaptation do not exist
      in the Ia-reflex-pathway components after a long-term stretching program as
      currently understood. Thus, any increases in flexibility are the result of other
      factors, potentially mechanical changes or stretch tolerance.

PMID- 22387807
TI  - Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other
      recreational drugs during pregnancy.
AB  - 3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy" is one of the most widely
      used illicit recreational drugs among young adults. MDMA is an indirect
      monoaminergic agonist and reuptake inhibitor that primarily affects the serotonin
      system. Preclinical studies in animals have found prenatal exposure related to
      neonatal tremors and long-term learning and memory impairments. To date, there
      are no prospective studies of the sequelae of prenatal exposure to MDMA in
      humans, despite concerns about its potential for harmful effects to the fetus.
      The present study is the first to prospectively identify MDMA-using women during
      pregnancy and to document patterns and correlates of use with neonatal and early
      infancy outcomes of offspring. All mothers and infants were prospectively
      recruited through the Case Western Reserve University (CWRU) and University of
      East London (UEL) Drugs and Infancy Study (DAISY) that focused on recreational
      drug use in pregnant women. Women were interviewed about substance use prior to
      and during pregnancy and infants were seen at 1 and 4 months using standardized,
      normative assessments of neonatal behavior, and cognitive and motor development,
      including the NICU Network Neurobehavioral Scale (NNNS), the Bayley Mental and
      Motor Development Scales (MDI, PDI), and the Alberta Infant Motor Scales (AIMS).
      The sample was primarily middle class with some university education and in
      stable partner relationships. The majority of women recruited had taken a number
      of illicit drugs prior to or during pregnancy. Group differences between those
      polydrug using women who had specifically used MDMA during pregnancy (n=28) and
      those who had not (n=68) were assessed using chi-square and t-tests. MDMA and
      other drug effects were assessed through multiple regression analyses controlling
      for confounding variables. Women who used MDMA during pregnancy had fewer prior
      births and more negative sequelae associated with their drug use, including more
      health, work, and social problems. MDMA exposed infants differed in sex ratio
      (more male births) and had poorer motor quality and lower milestone attainment at
      4 months, with a dose-response relationship to amount of MDMA exposure. These
      findings suggest risk to the developing infant related to MDMA exposure and
      warrant continued follow-up to determine whether early motor delays persist or
      resolve.

PMID- 22387832
TI  - Fluorescent probes for imaging endogenous beta-actin mRNA in living cells using
      fluorescent protein-tagged pumilio.
AB  - Subcellular localization and dynamics of mRNAs control various physiological
      functions in living cells. A novel technique for visualizing endogenous mRNAs in
      living cells is necessary for investigation of the spatiotemporal movement of
      mRNAs. A pumilio homology domain of human pumilio 1 (PUM-HD) is a useful RNA
      binding protein as a tool for mRNA recognition because the domain can be modified
      to bind a specific 8-base sequence of target mRNA. In this study, we designed PUM
      HD to match the sequence of beta-actin mRNA and developed an mRNA probe
      consisting of two PUM-HD mutants flanking full-length enhanced green fluorescent
      protein (EGFP). Fluorescence microscopy with the probe in living cells revealed
      that the probe was labeled precisely with the beta-actin mRNA in cytosol.
      Fluorescent spots from the probe were colocalized with microtubules and moved
      directionally in living cells. The PUM-HD mutants conjugated with full-length
      EGFP can enable visualization of beta-actin mRNA localization and dynamics in
      living cells.

PMID- 22387833
TI  - [Korean guidelines for colorectal cancer screening and polyp detection].
AB  - Colorectal cancer is the second most common cancer in males and the fourth most
      common in females in Korea. Since the most of colorectal cancer occur through the
      prolonged transformation of adenomas into carcinomas, early detection and removal
      of colorectal adenomas are one of the most effective methods to prevent
      colorectal cancer. Considering the increasing incidence of colorectal cancer and
      polyps in Korea, it is very important to establish Korean guideline for
      colorectal cancer screening and polyp detection. Korean Multi-Society Take Force
      developed the guidelines with evidence-based methods. Parts of the statements
      drawn by systematic reviews and meta-analyses. Herein we discussed the
      epidemiology of colorectal cancers and adenomas in Korea, optimal screening
      methods for colorectal cancer, and detection for adenomas including fecal occult
      blood tests, radiologic tests, and endoscopic examinations.

PMID- 22387834
TI  - [Korean guidelines for colonoscopic polypectomy].
AB  - There are indirect evidences to suggest that 80% of colorectal cancers (CRC)
      develop from adenomatous polyps and that, on average, it takes 10 years for a
      small polyp to transform into invasive CRC. In multiple cohort studies,
      colonoscopic polypectomy has been shown to significantly reduce the expected
      incidence of CRC by 76% to 90%. Colonoscopic polypectomy is performed frequently
      in primary, secondary and tertiary and medical centers in Korea. However, there
      are no evidence-based, procedural guidelines for the appropriate performance of
      this procedure, including the technical aspects. For the guideline presented
      here, Pubmed, Medline, and Cochrane Library literature searches were performed.
      When little or no data from well-designed prospective trials were available, an
      emphasis was placed on the results from large series and reports from recognized
      experts. Thus, these guidelines for colonoscopic polypectomy are based on a
      critical review of the available data as well as expert consensus. Further
      controlled clinical studies are needed to clarify aspects of this statement, and
      revision may be necessary as new data become available. This guideline is
      intended to be an educational device to provide information that may assist
      endoscopists in providing care to patients. This guideline is not a rule and
      should not be construed as a legal standard of care or as encouraging,
      advocating, requiring, or discouraging any particular treatment. Clinical
      decisions for any particular case involve a complex analysis of the patient's
      condition and the available courses of action.

PMID- 22387835
TI  - [Korean guidelines for post-polypectomy colonoscopic surveillance].
AB  - Post-polypectomy surveillance has become a major indication for colonoscopy as a
      result of increased use of screening colonoscopy in Korea. However, because the
      medical resource is limited, and the first screening colonoscopy produces the
      greatest effect on reducing the incidence and mortality of colorectal cancer,
      there is a need to increase the efficiency of postpolypectomy surveillance. In
      the present report, a careful analytic approach was used to address all available
      evidences to delineate the predictors for advanced neoplasia at surveillance
      colonoscopy. Based on the results of review of the evidences, we elucidated the
      high risk findings of the index colonoscopy as follows: 1) 3 or more adenomas, 2)
      any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any
      adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm.
      In patients without any high-risk findings at the index colonoscopy, surveillance
      colonoscopy should be performed five years after index colonoscopy. In patients
      with one or more high risk findings, surveillance colonoscopy should be performed
      three years after polypectomy. However, the surveillance interval can be
      shortened considering the quality of the index colonoscopy, the completeness of
      polyp removal, the patient's general condition, and family and medical history.
      This practical guideline cannot totally take the place of clinical judgments made
      by practitioners and should be revised and supplemented in the future as new
      evidence becomes available.

PMID- 22387836
TI  - [Guidelines for the management of ulcerative colitis].
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by
      a relapsing and remitting course. The quality of life can decreases significantly
      during exacerbations of the disease. The incidence and prevalence of UC in Korea
      are still lower than those of Western countries, but have been rapidly increasing
      during the past decades. Various medical and surgical therapies are currently
      used for the management of UC. However, many challenging issues exist and
      sometimes these lead to differences in practice between clinicians. Therefore,
      Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study
      of Intestinal Diseases (KASID) set out the Korean guidelines for the management
      of UC. These guidelines are made by the adaptation using several foreign
      guidelines and encompass treatment of active colitis, maintenance of remission
      and indication for surgery in UC. The specific recommendations are presented with
      the quality of evidence. These are the first Korean treatment guidelines for UC
      and will be revised with new evidences on treatment of UC.

PMID- 22387837
TI  - [Guidelines for the management of Crohn's disease].
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain
      etiopathogenesis. CD can involve any site of gastrointestinal tract from the
      mouth to anus and is associated with serious complications such as bowel
      strictures, perforations, and fistula formation. The incidence and prevalence
      rates of CD in Korea are still lower than those of Western countries, but have
      been rapidly increasing during the past decades. Although there are no definitive
      curative modalities for CD, various medical and surgical therapies are currently
      applied for diverse clinical situations of CD. However, a lot of decisions on the
      management of CD are made depending on the personal experiences and choices of
      physicians. To suggest preferable approaches to diverse problems of CD and to
      minimize the variations according to physicians, guidelines for the management of
      CD are needed. Therefore, IBD Study Group of the Korean Association for the Study
      of the Intestinal Diseases has set out to develop the guidelines for the
      management of CD in Korea. These guidelines were developed using the adaptation
      methods and encompass the treatment of inflammatory disease, stricturing disease,
      and penetrating disease. The guidelines also cover the indication of surgery,
      prevention of recurrence after surgery, and CD in pregnancy and lactation. These
      are the first Korean guidelines for the management of CD and the update with
      further scientific data and evidences is needed.

PMID- 22387838
TI  - [A case of afferent loop syndrome with acute cholangitis developed after
      percutaneous transhepatic cholangioscopic lithotripsy for treatment of
      choledocholithiasis in a patient who underwent Billroth II gastrectomy].
AB  - Afferent loop syndrome is a rare complication which can occur in patients with
      Billroth II gastrectomy. Bile and pancreatic juice is congested at afferent loop
      in the syndrome. This syndrome can progress rapidly to necrosis, perforation, or
      severe sepsis, and therefore early diagnosis and swift surgical intervention is
      important. But, cases of endoscopic or percutaneous transhepatic drainage have
      been reported when surgical management was inappropriate to proceed. We report a
      case of afferent loop syndrome accompanying acute cholangitis developed after
      percutaneous transhepatic cholangioscopic lithotripsy for the retrieval of common
      bile duct stone in a patient who underwent Billroth II gastrectomy due to early
      gastric cancer. There was no other organic cause. We treated afferent loop
      syndrome successfully by performing balloon dilation of afferent loop outlet.

PMID- 22387839
TI  - [A case of lateral abdominal wall hematoma treated with transcatheter arterial
      embolization].
AB  - Paracentesis is a diagnostic, therapeutic procedure performed in patients with
      ascites. It is generally thought to be a safe procedure and transfusion of
      platelet concentrate or fresh frozen plasma is not recommended before the
      procedure, because the incidence of clinically significant bleeding is very low.
      We report a case of lateral abdominal wall hematoma due to the injury of the deep
      circumflex iliac artery after paracentesis in patient with alcoholic liver
      cirrhosis who was treated with transcatheter arterial embolization.

PMID- 22387840
TI  - [A case of isolated hepatic lymphangioma].
AB  - Hepatic lymphangioma is a rare benign neoplasm. It usually occurs as a part of
      systemic lymphangiomatosis. Isolated hepatic lymphangioma is extremely rare. A 58
      year-old woman with weight loss was referred for the evaluation of chronic renal
      insufficiency and hepatic mass. Abdominal computed tomography showed 3 cm sized
      multilobulated cystic lesion with calcification and thick septal enhancing focus
      in the segment V of the liver. On abdominal magnetic resonance imaging, the
      masses exhibited low signal intensity on the T1-weighted images and high signal
      intensity on the T2-weighted images. Malignant tumor could not be ruled out, and
      therefore, the patient underwent right anterior segmentectomy of the liver. Gross
      pathology reveraled a 3.0*2.2*1.5 cm mass with multichamber cyst, which was
      filled with mucoid material. Histologically the mass was composed of irregularly
      shaped vascular channels filled acellular homogeneous lymph fluids. The final
      diagnosis was hepatic isolated cavernous lymphangioma. Herein, we report a case
      of isolated hepatic lymphangioma and also review the existing literature.

PMID- 22387841
TI  - [A case of splenic pseudocyst complicated by acute pancreatitis].
AB  - Splenic pseudocyst is a rare disease associated with chronic and acute
      pancreatitis splenic pseudocyst is treated by distal pancreatectomy and
      splenectomy. A 47-year old woman with a 10-year history of alcohol abuse
      presented with epigastric and left upper quadrant pain of 3 days duration.
      Abdominal CT showed a 4.0*4.5 cm sized cystic lesion in the tail of the pancreas.
      Analgesics was administrated for the relief of abdominal pain. On the 4th
      hospital day, the patient complained more of left upper quadrant pain, so we took
      follow up CT scans. On follow up CT, one large splenic pseudocyst with size of
      9.5*4.5*10.0 cm was noted. The patient was treated conservatively by percutaneous
      catheter drainage and discharged on the 13th hospital day. This case is the first
      case report of splenic pseudocyst treated conservatively, not by surgery in
      Korea.

PMID- 22387843
TI  - International prevalidation study on cell transformation assay. Preface.

PMID- 22387842
TI  - The use of next generation sequencing technology to study the effect of radiation
      therapy on mitochondrial DNA mutation.
AB  - The human mitochondrial genome has an exclusively maternal mode of inheritance.
      Mitochondrial DNA (mtDNA) is particularly vulnerable to environmental insults due
      in part to an underdeveloped DNA repair system, limited to base excision and
      homologous recombination repair. Radiation exposure to the ovaries may cause
      mtDNA mutations in oocytes, which may in turn be transmitted to offspring. We
      hypothesized that the children of female cancer survivors who received radiation
      therapy may have an increased rate of mtDNA heteroplasmy mutations, which
      conceivably could increase their risk of developing cancer and other diseases. We
      evaluated 44 DNA blood samples from 17 Danish and 1 Finnish families (18 mothers
      and 26 children). All mothers had been treated for cancer as children and
      radiation doses to their ovaries were determined based on medical records and
      computational models. DNA samples were sequenced for the entire mitochondrial
      genome using the Illumina GAII system. Mother's age at sample collection was
      positively correlated with mtDNA heteroplasmy mutations. There was evidence of
      heteroplasmy inheritance in that 9 of the 18 families had at least one child who
      inherited at least one heteroplasmy site from his or her mother. No significant
      difference in single nucleotide polymorphisms between mother and offspring,
      however, was observed. Radiation therapy dose to ovaries also was not
      significantly associated with the heteroplasmy mutation rate among mothers and
      children. No evidence was found that radiotherapy for pediatric cancer is
      associated with the mitochondrial genome mutation rate in female cancer survivors
      and their children.

PMID- 22387844
TI  - CycleTrak: a novel system for the semi-automated analysis of cell cycle dynamics.
AB  - Cell proliferation is crucial to tissue growth and form during embryogenesis, yet
      dynamic tracking of cell cycle progression and cell position presents a
      challenging roadblock. We have developed a fluorescent cell cycle indicator and
      single cell analysis method, called CycleTrak, which allows for better
      spatiotemporal resolution and quantification of cell cycle phase and cell
      position than current methods. Our method was developed on the basis of the
      existing Fucci method. CycleTrak uses a single lentiviral vector that integrates
      mKO2-hCdt1 (30/120), and a nuclear-localized eGFP reporter. The single vector and
      nuclear localized fluorescence signals simplify delivery into cells and allow for
      rapid, automated cell tracking and cell cycle phase readout in single and
      subpopulations of cells. We validated CycleTrak performance in metastatic
      melanoma cells and identified novel cell cycle dynamics in vitro and in vivo
      after transplantation and 3D confocal time-lapse imaging in a living chick
      embryo.

PMID- 22387845
TI  - Lens development depends on a pair of highly conserved Sox21 regulatory elements.
AB  - Highly conserved non-coding elements (CNEs) linked to genes involved in embryonic
      development have been hypothesised to correspond to cis-regulatory modules due to
      their ability to induce tissue-specific expression patterns. However, attempts to
      prove their requirement for normal development or for the correct expression of
      the genes they are associated with have yielded conflicting results. Here, we
      show that CNEs at the vertebrate Sox21 locus are crucial for Sox21 expression in
      the embryonic lens and that loss of Sox21 function interferes with normal lens
      development. Using different expression assays in zebrafish we find that two CNEs
      linked to Sox21 in all vertebrates contain lens enhancers and that their removal
      from a reporter BAC abolishes lens expression. Furthermore inhibition of Sox21
      function after the injection of a sox21b morpholino into zebrafish leads to
      defects in lens development. These findings identify a direct link between
      sequence conservation and genomic function of regulatory sequences. In addition
      to this we provide evidence that putative Sox binding sites in one of the CNEs
      are essential for induction of lens expression as well as enhancer function in
      the CNS. Our results show that CNEs identified in pufferfish-mammal whole-genome
      comparisons are crucial developmental enhancers and hence essential components of
      gene regulatory networks underlying vertebrate embryogenesis.

PMID- 22387847
TI  - Identification and functional analysis of mitochondrial complex I assembly factor
      homologues in C. elegans.
AB  - The biogenesis of mitochondrial NADH:ubiquinone oxidoreductase (complex I)
      requires several assembly chaperones. These so-called complex I assembly factors
      have emerged as a new class of human disease genes. Here, we identified putative
      assembly factor homologues in Caenorhabditis elegans. We demonstrate that two
      candidates (C50B8.3/NUAF-1, homologue of NDUFAF1 and R07H5.3/NUAF-3, homologue of
      NDUFAF3) clearly affect complex I function. Assembly factor deficient worms were
      shorter, showed a diminished brood size and displayed reduced fat content. Our
      results suggest that mitochondrial complex I biogenesis is evolutionarily
      conserved. Moreover, Caenorhabditis elegans appears to be a promising model
      organism to study assembly factor related human diseases.

PMID- 22387848
TI  - Fragrance material review on benzyl acetate.
AB  - A toxicologic and dermatologic review of benzyl acetate when used as a fragrance
      ingredient is presented. Benzyl acetate is a member of the fragrance structural
      group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance
      ingredients are prepared by reacting an aryl alkyl alcohol with a simple
      carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for benzyl acetate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity,
      toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, or
      carcinogenicity data. A safety assessment of the entire AAASAE will be published
      simultaneously with this document. Refer Belsito et al. (2012) for an overall
      assessment of the safe use of this material and all AAASAE in fragrances.

PMID- 22387853
TI  - Effects of sazetidine-A, a selective alpha4beta2* nicotinic receptor
      desensitizing agent, on body temperature regulation in mice and rats.
AB  - Nicotine-induced hypothermia is well established, but the nicotinic receptor
      actions underlying this effect are not clear. Nicotine causes activation and
      desensitization at a variety of nicotinic receptor subtypes. Sazetidine-A [6
      (5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound
      that potently and selectively desensitizes alpha4beta2* nicotinic receptors. The
      main goal of this study was to investigate the effects of sazetidine-A, on core
      body temperature (Tc) in mice and rats. Sazetidine-A effects on Tc and the
      interactions of sazetidine-A with nicotine and selective nicotinic antagonists
      were investigated to determine the receptor actions underlying nicotine-induced
      hypothermia. Adult male mice were injected with different dose of nicotine (0.2,
      0.4 and 0.8 mg/kg), sazetidine-A (0.3, 1, and 3mg/kg), a mixture of nicotine (0.4
      or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or saline and Tc was monitored
      telemetrically. In another set of experiments, the interaction between sazetidine
      A and dihydro-beta-erythroidine (DHbetaE), an alpha4beta2* nicotinic receptors
      antagonist, and methyllycaconitine (MLA), an alpha7 antagonist, was investigated.
      Tc of mice was monitored following DHbetaE (1, 3 and 6 mg/kg), a combination of
      DHbetaE (3mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6 mg/kg) or
      combination of MLA (6 mg/kg) and sazetidine (0.6 mg/kg) or saline. The acute
      effect of sazetidine-A (1, 3, and 6 mg/kg) on rats Tc was also studied. Acute
      sazetidine-A caused a pronounced and long-lasting hypothermia in mice; Tc
      decreased to about 28 degrees C at 100 min and recovered within 230 min. The
      hypothermic effect of sazetidine in rats was much less in magnitude (about 3
      degrees C) and shorter in duration compared with that in mice. Nicotine co
      administration with low doses of sazetidine potentiated the magnitude and
      duration of hypothermia in mice. The alpha4beta2* nicotinic receptors antagonist
      DHbetaE significantly prolonged sazetidine-A-induced hypothermia but did not
      increase its depth. The alpha7 antagonist MLA caused a modest degree of
      hypothermia with relatively short duration in mice. MLA failed to counteract the
      sazetidine-A-induced hypothermia. Overall, our results show that pharmacological
      modulation of alpha4beta2* nicotinic receptors elicits changes in body
      temperature that may involve desensitization of these receptors.

PMID- 22387854
TI  - Des-aspartate-angiotensin I exerts antiviral effects and attenuates ICAM-1
      formation in rhinovirus-infected epithelial cells.
AB  - The high frequency of rhinovirus (RV) infection and the lack of an effective
      treatment, underline the importance of research on novel anti-rhinoviral agents.
      The present study investigated the effects of des-aspartate-angiotensin I (DAA-I)
      on the survival of RV14-infected H1HeLa cells; and the early inflammatory
      processes in RV14-infected A549 lung epithelial cells. The study rationale was
      based on earlier findings showing that DAA-I is an effective anti-inflammatory
      agent, and that symptoms and severity of rhinoviral infection are related to the
      underling inflammation. RV14 concentration dependently caused the death of H1HeLa
      cells and DAA-I, at concentrations of 10-10 to 10-12 M, attenuated the lethal
      action of RV14 indicating that that DAA-I exerts antiviral action. Unlike its
      action on H1HeLa cells, RV14 did not cause apparent cytopathic effect on A549
      cells, and these cells were used to study the antiviral action of DAA-I. RV14
      induced overexpression of ICAM-1, E-selectin and overproduction of superoxide in
      A549 cells, and DAA-I attenuated the three increases to basal level at
      concentrations of 10-10 to 10-12 M. Losartan, an angiotensin AT1 receptor
      antagonist, blocked the inhibitory action of DAA-I on superoxide overproduction
      indicating that the AT1 receptor mediates the action of DAA-I. The present data
      represent a novel demonstration of the antiviral action of an angiotensin
      peptide, and a possible involvement of the renin angiotensin system in viral
      infection. Indeed the angiotensin AT1 receptor has been reported to be obligatory
      for the development of virus-induced myocardial injury through the
      proinflammatory action of angiotensin II via the NF-kappaB/cytokine pathway.

PMID- 22387855
TI  - Targeting glutamate system for novel antipsychotic approaches: relevance for
      residual psychotic symptoms and treatment resistant schizophrenia.
AB  - Antipsychotics are the mainstay of schizophrenia treatment. However,
      approximately one third of schizophrenic patients do not respond or respond
      poorly to antipsychotics. Therefore, there is a need for new approaches that can
      improve schizophrenia treatment significantly. Promising strategies arise from
      the modulation of glutamatergic system, according to its proposed involvement in
      schizophrenia pathogenesis. In this review, we critically updated preclinical and
      clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor
      activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines,
      mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results
      in animal models mimicking the pathophysiology of psychosis, mainly believed to
      be responsible of negative and cognitive symptoms, and predicting antipsychotic
      like activity of these compounds; and 2) clinical efficacy in open-label and
      double-blind trials. Albeit promising preclinical findings for virtually all
      compounds, clinical efficacy has not been confirmed for D-cycloserine.
      Contrasting evidence has been reported for glycine and D-serine, that may however
      have a role as add-on agents. More promising results in humans have been found
      for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro
      cognitive agents, while positive allosteric modulators of mGluR5 have not been
      tested in humans. Memantine has been proposed in early stages of schizophrenia,
      as it may counteract the effects of glutamate excitotoxicity correlated to high
      glutamate levels, slowing the progression of negative symptoms associated to more
      advanced stages of the illness.

PMID- 22387856
TI  - The effect of alendronate on the expression of osteopontin and osteoprotegerin in
      calcified aortic tissue of the rat.
AB  - Vascular calcification is a pathobiological process which leads to high morbidity
      and mortality in cardiovascular disease. The association between vascular
      calcification and osteoporosis has been reported widely, and there are close
      relationships among vascular calcification, related cardiovascular disease and
      osteoporosis, but the biochemical mechanism of vascular calcification is
      presently unclear. For exploring the possible mechanism of artery calcification
      we established aorta calcification in an animal model with vitamin D(3) and
      warfarin and tested the effect of alendronate on the expression of osteopontin
      and osteoprotegerin in calcified aorta tissue of the rat through measuring gene
      and protein expression of osteopontin and osteoprotegerin respectively. The
      results indicated compared with control group, the aortic calcium content of
      calcification group was obviously increased, osteopontin mRNA and osteoprotegerin
      mRNA were significantly reduced, and osteoprotegerin and osteopontin protein
      expressions were reduced. Compared with calcification group, the aortic calcium
      content of alendronate group was obviously reduced, osteopontin mRNA and
      osteoprotegerin mRNA were significantly increased, and osteopontin and
      osteoprotegerin protein expression were increased. We conclude that artery
      calcification may reduce the expression of osteopontin and osteoprotegerin.
      Alendronate may inhibit rat aorta calcification by up-regulating osteopontin and
      osteoprotegerin expression.

PMID- 22387857
TI  - Thiamine is a substrate of organic cation transporters in Caco-2 cells.
AB  - The aim of this study was to characterize the intestinal absorption of thiamine,
      by investigating the hypothesis of an involvement of Organic Cation Transporter
      (OCT) family members in this process. [(3)H]-T(+) uptake was found to be: 1) time
      dependent, 2) Na(+)- and Cl(-)-dependent, 3) pH-dependent, with uptake increasing
      with a decrease in extracellular pH and decreasing with a decrease in
      intracellular pH, 4) inhibited by amiloride, 5) inhibited by the thiamine
      structural analogues oxythiamine and amprolium, 6) inhibited by the unrelated
      organic cations MPP(+), clonidine, dopamine, serotonin, 7) inhibited by the OCT
      inhibitors decynium22 and progesterone. Moreover, the dependence of [(3)H]-T(+)
      uptake on phosphorylation/dephosphorylation mechanisms was also investigated and
      [(3)H]-T(+) uptake was found to be reduced by PKA activation and protein tyrosine
      phosphatase and alkaline phosphatase inhibition. In conclusion, our results are
      compatible with the possibility of thiamine being transported not only by ThTr1
      and/or ThTr2, but also by members of the OCT family of transporters (most
      probably OCT1 and/or OCT3), thus sharing the same transporters with several other
      organic cations at the small intestinal level.

PMID- 22387858
TI  - Evidence for the involvement of the monoaminergic system, but not the opioid
      system in the antidepressant-like activity of ellagic acid in mice.
AB  - Dietary flavonoids possess a multiplicity of neuroprotective actions in various
      central nervous pathophysiological conditions including depression. Ellagic acid
      is a polyphenolic compound that occurs in plants such as raspberries, nuts and
      eucalyptus species. The present study was designed to investigate the
      antidepressant-like effect of ellagic acid in mice using forced swimming test
      (FST) and tail suspension test (TST). The involvement of the monoaminergic and
      opioid systems in the antidepressant-like activity of ellagic acid was also
      studied. Our results showed that ellagic acid when administered acutely or
      chronically to mice (25, 50 and 100mg/kg, p.o.), produced a significant reduction
      in the duration of immobility, with a profile comparable to that of fluoxetine
      (20mg/kg, p.o.). However, ellagic acid treatment had no effect on the locomotor
      activity of mice when tested in actophotometer. The reduction in immobility time
      observed with ellagic acid treatment (50mg/kg, p.o.) was prevented by
      pretreatment with p-chlorophenylalanine (100mg/kg, i.p., a serotonin synthesis
      inhibitor), pindolol (10mg/kg, i.p., a beta-adrenoceptors blocker/5HT(1A/1B)
      receptor antagonist), ketanserin (5mg/kg, i.p., a 5HT(2A/2B) receptor
      antagonist), ondansetron (1mg/kg, i.p., a 5HT(3) receptor antagonist), prazosin
      (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p.,
      an alpha(2)-adrenoceptor antagonist), but not with naloxone (1mg/kg, i.p., an
      opioid receptor antagonist). Our results suggest that ellagic acid produced an
      antidepressant-like effect which was unrelated to its locomotor activity.
      Furthermore, this anti-immobility effect seems most likely to be mediated through
      an interaction with the monoaminergic system (serotonergic and noradrenergic
      systems) and not through the opioid system.

PMID- 22387859
TI  - Metyrapone effects on systemic and cerebral energy metabolism.
AB  - Metyrapone is a cytochrome P(450) inhibitor that protects against ischemia- and
      excitotoxicity-induced brain damages in rodents. This study examines whether
      metyrapone would act on energy metabolism in a manner congruent with its
      neuroprotective effect. In a first investigation, the rats instrumented with
      telemetric devices measuring abdominal temperature, received i.p. injection of
      either metyrapone or saline. One hour after injection, their blood and
      hippocampus were sampled. Hippocampus metabolite concentrations were measured
      using (1)H high-resolution magic angle spinning-magnetic resonance spectroscopy
      ((1)H HRMAS-MRS). The hippocampus levels in phosphorylated mammalian target of
      rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) were
      measured by Western Blot analysis and those of c-fos and HSP70-2 mRNA were
      quantified by RT-PCR. In a second investigation, the rats received the same
      treatment and were sacrificed 1h after. The functioning of mitochondria was
      immediately studied on their whole brain. Metyrapone provoked a slight
      hypothermia which was correlated to the increase in blood glucose concentration.
      Metyrapone also increased blood lactate concentrations without modifying
      hippocampus lactate content. In the hippocampus, metyrapone decreased gamma
      aminobutyric acid (GABA) and glutamate levels but increased glutamine and N
      acetyl-aspartate contents (NAA). Phosphorylated mTOR and AMPK and the c-fos and
      HSP70-2 mRNA levels were similar between treatment groups. Metyrapone did not
      modify blood corticosterone levels. Mitochondrial oxygen consumption was similar
      in both groups whatever the substrate used. These metabolic modifications, which
      take place without modifying blood glucocorticoid levels, are consistent with the
      neuroprotective properties of metyrapone as demonstrated in animal models.

PMID- 22387860
TI  - Reduction of renal lipid content and proteinuria by a PPAR-gamma agonist in a rat
      model of angiotensin II-induced hypertension.
AB  - An excess of lipids may accumulate in the kidney in conditions such as diabetes
      and hypertension, and can potentially cause renal injury. We previously reported
      that an infusion of angiotensin II into a rat induced deposition of lipids in the
      renal tubular epithelial cells. Here we have examined the effect of pioglitazone,
      an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma),
      on renal lipid accumulation and renal injury induced by angiotensin II infusion.
      Pioglitazone treatment (2.5mg/kg/day) reduced the amount of triglycerides in the
      kidney of the angiotensin II-induced hypertensive rat without significantly
      altering either blood pressure levels or mRNA expression of lipogenic genes in
      the kidney. In addition, pioglitazone, either alone or in conjunction with
      angiotensin II, increased the expression of phosphorylated, but not total, AMP
      activated protein kinase (AMPK). Proteinuria and kidney weight in the angiotensin
      II-infused rat were significantly decreased by pioglitazone treatment. In
      addition, pioglitazone suppressed iron deposition and ferritin protein induction,
      but did not alter upregulated expression of the antioxidative molecule, heme
      oxygenase-1, in the kidney of the angiotensin II-infused rat. These findings
      suggested that pioglitazone suppressed the angiotensin II-induced increase in
      renal lipid content by inhibiting its proteinuric action, but not by direct
      alteration of the expression or activity of lipid metabolism-related genes.
      Reduction of lipotoxic renal damage may represent one of the renoprotective
      effects provided by pioglitazone in hypertension with activation of the renin
      angiotensin system.

PMID- 22387861
TI  - C-Terminal region of 48-kDa rhoptry protein for serological detection of Babesia
      caballi antibodies in horses.
AB  - A recombinant C-terminal antigen derived from Babesia caballi 48-kDa rhoptry
      protein (rBc48/CT) was made for the development of a serologically diagnostic
      test. Antiserum raised against the rBc48/CT reacted specifically with the
      corresponding native protein by Western blotting and the indirect fluorescent
      antibody test (IFAT). Next, an indirect enzyme-linked immunosorbent assay
      (Bc48/CT-ELISA) and an immunochromatographic test based on the Bc48/CT (Bc48/CT
      ICT) were constructed and employed for the detection of an antibody to B. caballi
      in a variety of equine sera. The results of Bc48/CT-ELISA and Bc48/CT-ICT were
      highly concordant with those of IFAT and ELISA, with full-length protein of Bc48
      used as the reference tests. Our results demonstrate the success of Bc48/CT as
      antigen for the serological diagnosis of B. caballi infection in horses.

PMID- 22387862
TI  - Phylogenetic relationships of rat lungworm, Angiostrongylus cantonensis, isolated
      from different geographical regions revealed widespread multiple lineages.
AB  - We conducted a pilot survey of genetic variation of A. cantonensis using small
      subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I
      (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified
      among 17 individual A. cantonensis worms from 17 different geographical
      localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI
      sequences were determined for 83 worms from 18 different geographical localities
      from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed
      eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a
      single coxI haplotype was found. However, in two localities, two coxI haplotypes
      coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba,
      Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen,
      and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and
      haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated
      from the others by high mountain ranges or oceans. In addition, the lower genetic
      variation and particular geographical distribution of A. cantonensis in each
      location could indicate a founder effect, which may have resulted from multiple
      independent origins, and suggests that haplotypes migrated from endemic areas via
      human-related transportation.

PMID- 22387875
TI  - Effect of a 6-week strengthening program on shoulder and scapular-stabilizer
      strength and scapular kinematics in division I collegiate swimmers.
AB  - CONTEXT: Shoulder injuries are common in swimmers because of the demands of the
      sport. Muscle imbalances frequently exist due to the biomechanics of the sport,
      which predispose swimmers to injury. To date, an effective shoulder-injury
      prevention program for competitive swimmers has not been established. OBJECTIVE:
      To assess the effectiveness of a 6-wk strengthening and stretching intervention
      program on improving glenohumeral and scapular muscle strength and scapular
      kinematics in collegiate swimmers. DESIGN: Randomized control trial. SETTING:
      University biomechanics research laboratory. PARTICIPANTS: Forty-four Division I
      collegiate swimmers. INTERVENTIONS: The intervention program was completed 3
      times per week for 6 wk. The program included strengthening exercises completed
      using resistance tubing-scapular retraction (Ts), scapular retraction with upward
      rotation (Ys), scapular retraction with downward rotation (Ws), shoulder flexion,
      low rows, throwing acceleration and deceleration, scapular punches, shoulder
      internal rotation at 90 degrees  abduction, and external rotation at 90 degrees 
      abduction-and 2 stretching exercises: corner stretch and sleeper stretch. MAIN
      OUTCOME MEASUREMENTS: Scapular kinematics and glenohumeral and scapular muscle
      strength assessed preintervention and postintervention. RESULTS: There were no
      significant between-groups differences in strength variables at pre/post tests,
      although shoulder-extension and internal-rotation strength significantly
      increased in all subjects regardless of group assignment. Scapular kinematic data
      revealed increased scapular internal rotation, protraction, and elevation in all
      subjects at posttesting but no significant effect of group on the individual
      kinematic variables. CONCLUSIONS: The current strengthening and stretching
      program was not effective in altering strength and scapular kinematic variables
      but may serve as a framework for future programs. Adding more stretching
      exercises, eliminating exercises that overlap with weight-room training and swim
      training, and timing of implementation may yield a more beneficial program for
      collegiate swimmers.

PMID- 22387877
TI  - Vitellogenin-like proteins in the freshwater amphipod Gammarus fossarum (Koch,
      1835): functional characterization throughout reproductive process, potential for
      use as an indicator of oocyte quality and endocrine disruption biomarker in
      males.
AB  - This work focused on the validation of biological specificity of the quantitative
      LC-MS/MS assay by checking the natural variability of Vg levels during the
      reproductive cycle in Gammarus fossarum (i.e., including oogenesis and
      embryogenesis). Laboratory tests were performed for 21 days under controlled
      conditions to assess Vg changes in male and female gammarids after exposure to
      chemical stress. Females were exposed to two crustacean hormones, 20
      hydroxyecdysone (0.01, 1 and 100 MUg L-1) and methyl-farnesoate (0.01, 1 and 100
      MUg L-1). No effect was recorded for 20-hydroxyecdysone, whereas in females
      exposed to methyl-farnesoate a deleterious impact on Vg production was observed.
      Males were exposed to crustacean hormones 20-hydroxyecdysone (0.01, 1 and 100 MUg
      L-1) and methyl-farnesoate (0.01, 1 and 100 MUg L-1), the insecticide
      methoxyfenozide (0.001, 0.1 and 10 MUg L-1), the fungicide propiconazole (0.001,
      0.1, 10 and 1000 MUg L-1), and the pharmaceutical products benzophenone,
      carbamazepine, cyproterone, and R-propranolol (0.001, 0.1, 10 and 1000 MUg L-1).
      Induction of Vg synthesis was recorded in males exposed to cyproterone,
      methoxyfenozide, methyl-farnesoate, and propiconazole. Finally, we validated the
      function of the ILIPGVGK peptide used to track vitellogenin in G. fossarum across
      reproductive processes (vitellogenesis and embryogenesis), and results confirmed
      the energy reserve role of Vg during embryo development. We show that oocyte
      surface measurement is directly related to Vg levels in the oocyte, constituting
      a reliable indicator of egg quality in G. fossarum. Consequently, it could be
      used as a reliable tool for biomonitoring programs. We recorded induction of Vg
      in male G. fossarum; however, the possible use of this tool as a specific
      biomarker of exposure to endocrine disruption should be confirmed in further
      studies.

PMID- 22387878
TI  - Ecotoxicological impacts of effluents generated by oil sands bitumen extraction
      and oil sands lixiviation on Pseudokirchneriella subcapitata.
AB  - The exploitation of Athabasca oil sands deposits in northern Alberta has known an
      intense development in recent years. This development has raised concern about
      the ecotoxicological risk of such industrial activities adjacent to the Athabasca
      River. Indeed, bitumen extraction generated large amounts of oil sands process
      affected water (OSPW) which are discharged in tailing ponds in the Athabasca
      River watershed. This study sought to evaluate and compare the toxicity of OSPW
      and oil sands lixiviate water (OSLW) with a baseline (oil sands exposed to water;
      OSW) on a microalgae, Pseudokirchneriella subcapitata, at different
      concentrations (1.9, 5.5, 12.25, 25 and 37.5%, v/v). Chemical analyses of water
      soluble contaminants showed that OSPW and OSLW were enriched in different
      elements such as vanadium (enrichment factor, EF=66 and 12, respectively),
      aluminum (EF=64 and 15, respectively), iron (EF=52.5 and 17.1, respectively) and
      chromium (39 and 10, respectively). The toxicity of OSPW on cells with optimal
      intracellular esterase activity and chlorophyll autofluorescence (viable cells)
      (72h-IC 50%<1.9%) was 20 times higher than the one of OSW (72h-IC 50%>37.5%,
      v/v). OSLW was 4.4 times less toxic (IC 50%=8.5%, v/v) than OSPW and 4.5 times
      more toxic than OSW. The inhibition of viable cell growth was significantly and
      highly correlated (<-0.7) with the increase of arsenic, beryllium, chromium,
      copper, lead, molybdenum and vanadium concentrations. The specific photosynthetic
      responses studied with JIP-test (rapid and polyphasic chlorophyll a fluorescence
      emission) showed a stimulation of the different functional parameters (efficiency
      of PSII to absorb energy from photons, size of effective PSII antenna and
      vitality of photosynthetic apparatus for energy conversion) in cultures exposed
      to OSPW and OSLW. To our knowledge, our study highlights the first evidence of
      physiological effects of OSPW and OSLW on microalgae.

PMID- 22387879
TI  - Virtual sources and sinks during extracellular field shocks in cardiac cell
      cultures: effects of source-sink interactions between adjacent tissue boundaries.
AB  - BACKGROUND: One mechanism by which extracellular field shocks (ECFSs)
      defibrillate the heart is by producing changes in membrane potential (V(m)) at
      tissue discontinuities. Such virtual electrodes may produce new excitation waves
      or affect locally propagating action potentials. The rise time of V(m) determines
      the required duration of a single defibrillation pulse to reach a critical
      threshold for activation or for the modification of ion channel function, and
      depends on the electric and microstructural characteristics of the tissue.
      METHODS AND RESULTS: We used optical mapping of V(m) in patterned cultures of
      neonatal rat ventricular myocytes to assess the relationship between cardiac
      structure and the early time course of V(m) during ECFSs. At monolayer
      boundaries, the time course of V(m) showed a close fit to the theoretical change
      predicted by theory, with a membrane time constant of 2.65+/-0.19 ms (n=13) and a
      length constant of 159+/-6 MUm (n=10). Experiments in patterned strands,
      mimicking the resistive boundaries that occur naturally in the heart, explained
      the observation that the rate of rise and the maximal amplitudes of the V(m)
      changes are inversely related because of electrotonic interactions between
      structural boundaries. Interrupting ECFSs by very short intervals diminished
      V(m), but did not cause major changes in its overall time course. CONCLUSIONS:
      Interaction between virtual sinks and sources decreases the magnitude of the
      changes in V(m) but accelerates its time course. For efficient defibrillation,
      short ECFSs are needed, with an amplitude adapted to match the boundary
      interaction.

PMID- 22387880
TI  - RNAi knockdown of the Akt1 gene increases the chemosensitivity of gastric cancer
      cells to cisplatin both in vitro and in vivo.
AB  - AIM: To examine the in vitro and in vivo effects of a combined treatment of cis-d
      iamminedichloroplatinum(II) (cisplatin) with downregulation of Akt1 expression in
      gastric cancer cells. MATERIALS AND METHODS: Lentivirus-mediated RNA interference
      (RNAi) was used to silence the Akt1 gene. pGCSIL-Akt1 small hairpin RNA (shRNA)
      was stably transfected into gastric cancer cells (SGC7901 and BGC823). Next, the
      effects of Akt1 downregulation on the growth and apoptosis of SGC7901 (BGC823)
      cells in the presence or absence of cisplatin were investigated by real-time
      polymerase chain reaction (RT-PCR), Western blot analysis, MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-d-iphenyltetrazolium bromide) assay, Hoechst assay,
      flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL (terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling). Finally, the
      effects of downregulation of Akt1 expression on the sensitivity of SGC7901 cells
      in a tumor xenograft model of cisplatin were also determined. RESULT: Akt1
      silencing reduced gastric cancer proliferation and increased cell apoptosis both
      in vitro and in vivo. The chemosensitivity of SGC7901 (BGC823) cells to cisplatin
      increased significantly following the downregulation of Akt1 expression, which
      might be associated with the inactivation of the PI3K/Akt1 signaling pathway,
      followed by the induced expression of the pro-apoptotic protein Bax and a
      concomitant decrease of Bcl-2 expression. CONCLUSION: This study confirmed that
      downregulation of Akt1 reduced chemotherapy tolerance of gastric cancer cells to
      cisplatin treatment. Thus, Akt1 silencing and cisplatin appear to be an effective
      combination treatment strategy for gastric cancer.

PMID- 22387881
TI  - Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene
      polymorphisms are associated with human sperm concentration.
AB  - Choline is a crucial factor in the regulation of sperm membrane structure and
      fluidity, and this nutrient plays an important role in the maturation and
      fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N
      methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of
      choline metabolism, have been observed in the human testis, demonstrating their
      gene expression in this tissue. In the present study, we explored the
      contribution of the PEMT and CHDH gene variants to sperm parameters. Two hundred
      oligospermic and 250 normozoospermic men were recruited. DNA was extracted from
      the spermatozoa, and the PEMT -774G>C and CHDH +432G>T polymorphisms were
      genotyped. The genotype distribution of the PEMT -774G>C polymorphism did not
      differ between oligospermic and normozoospermic men. In contrast, in the case of
      the CHDH +432G>T polymorphism, oligospermic men presented the CHDH 432G/G
      genotype more frequently than normozoospermic men (62% vs. 42%, P<0.001). The
      PEMT 774G/G genotype was associated with a higher sperm concentration compared to
      the PEMT 774G/C and 774C/C genotypes in oligospermic men (12.5 +/- 5.6 * 10(6)
      spermatozoa ml(-1) vs. 8.3 +/- 5.2 * 10(6) spermatozoa ml(-1), P<0.002) and
      normozoospermic men (81.5 +/- 55.6 * 10(6) vs. 68.1 +/- 44.5 * 10(6) spermatozoa
      ml(-1), P<0.006). In addition, the CHDH 432G/G genotype was associated with
      higher sperm concentration compared to CHDH 432G/T and 432T/T genotypes in
      oligospermic (11.8 +/- 5.1 * 10(6) vs. 7.8 +/- 5.3 * 10(6) spermatozoa ml(-1),
      P<0.003) and normozoospermic men (98.6 +/- 62.2 * 10(6) vs. 58.8 +/- 33.6 * 10(6)
      spermatozoa ml(-1), P<0.001). In our series, the PEMT -774G>C and CHDH +432G>T
      polymorphisms were associated with sperm concentration. This finding suggests a
      possible influence of these genes on sperm quality.

PMID- 22387882
TI  - The novel endocrine disruptor tolylfluanid impairs insulin signaling in primary
      rodent and human adipocytes through a reduction in insulin receptor substrate-1
      levels.
AB  - Emerging data suggest that environmental endocrine disrupting chemicals may
      contribute to the pathophysiology of obesity and diabetes. In a prior work, the
      phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte
      differentiation, yet its effects on mature adipocyte metabolism remain unknown.
      Because of the central role of adipose tissue in global energy regulation, the
      present study tested the hypothesis that TF modulates insulin action in primary
      rodent and human adipocytes. Alterations in insulin signaling in primary
      mammalian adipocytes were determined by the phosphorylation of Akt, a critical
      insulin signaling intermediate. Treatment of primary murine adipose tissue in
      vitro with 100nM TF for 48h markedly attenuated acute insulin-stimulated Akt
      phosphorylation in a strain- and species-independent fashion. Perigonadal,
      perirenal, and mesenteric fat were all sensitive to TF-induced insulin
      resistance. A similar TF-induced reduction in insulin-stimulated Akt
      phosphorylation was observed in primary human subcutaneous adipose tissue. TF
      treatment led to a potent and specific reduction in insulin receptor substrate-1
      (IRS-1) mRNA and protein levels, a key upstream mediator of insulin's diverse
      metabolic effects. In contrast, insulin receptor-beta, phosphatidylinositol 3
      kinase, and Akt expression were unchanged, indicating a specific abrogation of
      insulin signaling. Additionally, TF-treated adipocytes exhibited altered
      endocrine function with a reduction in both basal and insulin-stimulated leptin
      secretion. These studies demonstrate that TF induces cellular insulin resistance
      in primary murine and human adipocytes through a reduction of IRS-1 expression
      and protein stability, raising concern about the potential for this fungicide to
      disrupt metabolism and thereby contribute to the pathogenesis of diabetes.

PMID- 22387884
TI  - Anti-proliferative effect of atrial natriuretic peptide on colorectal cancer
      cells: evidence for an Akt-mediated cross-talk between NHE-1 activity and
      Wnt/beta-catenin signaling.
AB  - Acidic tumor microenvironment and Wnt/beta-catenin pathway activation have been
      recognized as two crucial events associated with the initiation and progression
      of cancer. The aim of this study was to clarify the molecular mechanisms
      underlying the anti-proliferative effects of atrial natriuretic peptide (ANP) as
      well as to investigate the relationship between the cellular pH and the Wnt/beta
      catenin signaling in cancer cells.To pursue our aims, we conducted investigations
      in DHD/K12/Trb rat colon adenocarcinoma cells. Intracellular pH was measured by
      Confocal Laser Scanning Microscopy (CLSM) using the lysosensor Green DND-189
      probe. Expression of crucial molecules in the Wnt/beta-catenin signaling pathway
      was analyzed by CLSM, western blot, and real time PCR. Measurements of activation
      (phosphorylation state) of Akt, ERK1/2, and p38MAPKinase were performed by
      Reverse-Phase Protein Microarray Analysis (RPMA).We showed that ANP triggered a
      NHE-1-mediated increase of the intracellular acidity, inhibiting the Wnt/beta
      catenin signaling simultaneously. Moreover, we observed that the Wnt1a, a Wnt
      signaling activator, affected the intracellular pH in an opposite fashion.
      Results from the comparative analysis of ANP and EIPA (a NHE-1 specific
      inhibitor) showed that these two molecules affect both the intracellular
      acidification and the Wnt/beta-catenin signaling cascade. Specifically, ANP acts
      on the upstream of the cascade, through a Frizzled-mediated activation, while
      EIPA does on the downstream.We show for the first time that the Akt activity
      might be a relevant molecular event linking the NHE-1-regulated intracellular pH
      and the Wnt/beta-catenin signaling. This provides evidence for a cross-talk
      between the intracellular alkalinization and the Wnt signaling in tumor cells.

PMID- 22387883
TI  - Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and
      mitochondrial deficiencies.
AB  - The objective of this study was to elucidate the effect of partial reduction of
      the mitochondrial fission protein, dynamin-related protein 1 (Drp1) on
      mitochondrial activity and synaptic viability. Recent knockout studies of Drp1
      revealed that homozygote Drp1 knockout mice are embryonic lethal due to reduced
      mitochondrial fission, and that this reduced fission leads to developmental
      defects in the brain. In contrast, heterozygote Drp1 knockout mice appear to be
      normal in terms of lifespan, fertility, and viability, and phenotypically these
      animals are not different from wild-type mice. However, the effects of partial
      Drp1 reduction on mitochondrial function and synaptic activity are not well
      understood. In the present study, we sought to characterize synaptic, dendritic
      and mitochondrial proteins, and mitochondrial function and GTPase enzymatic
      activity, in Drp1 heterozygote knockout mice. Interestingly, we found no
      significant changes in synaptic, dendritic, and mitochondrial proteins in the
      Drp1 heterozygote knockout mice compared to the wild-type mice. Further,
      mitochondrial function and GTPase enzymatic activity appeared to be normal.
      However, H(2)O(2) and lipid peroxidation levels were significantly reduced in the
      Drp1 heterozygote knockout mice compared to the wild-type mice. These findings
      suggest that partial Drp1 reduction does not affect mitochondrial and synaptic
      viability and may have therapeutic use in treating patients with Alzheimer's
      disease and Huntington's disease.

PMID- 22387885
TI  - Indoleamine 2,3-dioxygenase expression in human inflammatory bowel disease.
AB  - OBJECTIVE: The study is carried out to identify the expression pattern of
      indoleamine 2,3-dioxygenase (IDO) in human Crohn's disease and ulcerative colitis
      and to investigate the effect of different therapies (salicylates, steroids, and
      antitumor necrosis factor antibody) on the intestinal expression of IDO. METHODS:
      Immunohistochemistry was used. A total of 10 high power fields were counted for
      each patient. RESULTS: IDO was expressed in the both lamina propria and
      epithelium. IDO expression increased in the lesions from ulcerative colitis and
      Crohn's disease and was positively related to the severity of inflammation. IDO
      positive mononuclear cells also expressed CD11c, CD68, and TLR4. IDO expression
      decreased significantly after treatment with steroids and salicylates, but
      remained unchanged after infliximab therapy. CONCLUSION: IDO was over-expressed
      in human inflammatory bowel disease. It may be a bridge between innate immunity
      and adaptive immunity. Steroids and salicylates may act through the inhibition of
      IDO expression. IDO upregulation may be a promising therapy to achieve
      inflammatory bowel disease remission.

PMID- 22387886
TI  - Survival from digestive cancer in emerging countries in Asia and Africa.
AB  - The incidence of digestive cancer, including cancer of the esophagus, stomach,
      colon, and liver, is analyzed in developing and less developed countries in
      Africa, Asia, the Caribbean, and Latin America. The analysis is based on cancer
      registries for observed values, on a recent monograph published at International
      Agency for Research on Cancer and on the GLOBOCAN 2008 database for estimations.
      For all tumor sites analyzed, the incidence is lower in these countries than in
      developed countries of Europe, North America, and Japan. The 5-year relative
      survival from digestive cancer is also lower. In developing countries, there is
      room for prevention of cancer burden through lifestyle interventions and through
      improved early detection of cancer.

PMID- 22387887
TI  - The impact of infliximab induction therapy on mucosal healing and clinical
      remission in Polish pediatric patients with moderate-to-severe Crohn's disease.
AB  - OBJECTIVE: To assess the clinical efficacy and the impact of infliximab (IFX)
      induction therapy on mucosal healing in Polish children with Crohn's disease
      (CD). METHODS: A total of 66 children (29 boys and 37 girls) aged 14.06 +/- 3.59
      years with CD diagnosed at the mean age of 8.4 +/- 7.3 years were included in the
      study. Patients received IFX (5 mg/kg) in three repeated infusions at 0, 2, and 6
      weeks. The clinical activity of the disease was assessed using the Pediatric
      Crohn's Disease Activity Index (PCDAI) and the endoscopic activity was scored
      using the Simple Endoscopic Score for Crohn's disease at baseline and at week 10.
      RESULTS: Twenty-two (33%) of the studied patients reached clinical remission
      (PCDAI <= 10), 26 (39%) showed a clinical response (PCDAI between 15 and 30), and
      18 (28%) did not respond to the therapy. When comparing data at baseline and at
      week 10, significant decreases were observed in the median PCDAI, C-reactive
      protein, and platelet count. In addition, a significant increase in BMI was
      noted. A significant decrease in the Simple Endoscopic Score for CD was observed
      between the initial and the control colonoscopies. Fifteen out of 66 patients
      (22.7%) had score 0 in the control endoscopy at week 10. No adverse events
      leading to therapy termination were observed. CONCLUSION: Biological therapy with
      IFX enables mucosal healing in pediatric patients with CD. Induction therapy with
      infliximab was found to be clinically effective in 72% of Polish pediatric
      patients with CD and induced a remission in 33% of them. Induction therapy with
      infliximab helps to increase BMI.

PMID- 22387888
TI  - Suppression of efflux transporters in the intestines of endotoxin-treated rats.
AB  - Infection and inflammation suppress the expression and activity of several drug
      transporters in the liver. In the intestine, P-glycoprotein (PGP/mdr1) and the
      multidrug resistance-associated protein 2 (MRP2) are important barriers to the
      absorption of many clinically important drugs. The protein expression and
      activity of these transporters were examined during inflammation induced by
      lipopolysaccharide (LPS). The transport of rhodamine123 (Rho123) and 5
      carboxyfluorescein (5-CF) was determined in isolated ileal segments from
      endotoxin-treated or control rats in the presence or absence of inhibitors. The
      reverse transcription-polymerase chain reaction was used to measure mRNA levels.
      Compared with the controls, the mRNA levels of mdr1a and mrp2 were significantly
      decreased by approximately 50% in the ilea of the LPS-treated rats. Corresponding
      reductions in the basolateral-apical efflux of Rho123 and 5-CF were observed,
      resulting in significant increases in the apical-basolateral absorption of these
      compounds. Neither the permeability of fluorescein isothiocyanate labeled dextran
      4000 (FD-4), a paracellular marker, nor membrane resistance was altered. These
      results indicate that endotoxin-induced inflammation reduces the intestinal
      expression and activity of PGP and MRP2 in rats, which eliciting corresponding
      changes in the intestinal transport of their substrates. Hence, infection and
      inflammatory diseases may induce variability in drug bioavailability through
      alterations in the intestinal expression and activity of drug transporters.

PMID- 22387901
TI  - Downregulation of miR-210 expression inhibits proliferation, induces apoptosis
      and enhances radiosensitivity in hypoxic human hepatoma cells in vitro.
AB  - Hypoxia is a common feature of solid tumors and an important contributor to tumor
      radioresistance. miR-210 is the most consistently and robustly induced microRNA
      under hypoxia in different types of tumor cells and normal cells. In the present
      study, to explore the feasibility of miR-210 as an effective therapeutic target,
      lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to
      downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and
      HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an
      increased hypoxia inducible factor-1alpha (HIF-1alpha) and miR-210 expression and
      cell arrest in the G(0)/G(1) phase in all cell lines. miR-210 downregulation
      significantly suppressed cell viability, induced cell arrest in the G(0)/G(1)
      phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human
      hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3
      (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation
      by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic
      human hepatoma cells. Taken together, these data suggest that miR-210 might be a
      potential therapeutic target and specific inhibition of miR-210 expression in
      combination with radiotherapy might be expected to exert strong anti-tumor effect
      on hypoxic human hepatoma cells.

PMID- 22387916
TI  - Genetic analysis of the Bacillus licheniformis degSU operon and the impact of
      regulatory mutations on protease production.
AB  - Disruption experiments targeted at the Bacillus licheniformis degSU operon and
      GFP-reporter analysis provided evidence for promoter activity immediately
      upstream of degU. pMutin mediated concomitant introduction of the degU32 allele-
      known to cause hypersecretion in Bacillus subtilis-- resulted in a marked
      increase in protease activity. Application of 5-fluorouracil based
      counterselection through establishment of a phosphoribosyltransferase deficient
      Deltaupp strain eventually facilitated the marker-free introduction of degU32
      leading to further protease enhancement achieving levels as for hypersecreting
      wild strains in which degU was overexpressed. Surprisingly, deletion of rapG-
      known to interfere with DegU DNA-binding in B. subtilis--did not enhance protease
      production neither in the wild type nor in the degU32 strain. The combination of
      degU32 and Deltaupp counterselection in the type strain is not only equally
      effective as in hypersecreting wild strains with respect to protease production
      but furthermore facilitates genetic strain improvement aiming at biological
      containment and effectiveness of biotechnological processes.

PMID- 22387918
TI  - iGel supraglottic airway use during hospital cardiopulmonary resuscitation.

PMID- 22387919
TI  - Verification of endotracheal tube placement using ultrasound during emergent
      intubation of a preterm infant.

PMID- 22387920
TI  - Comparison of normal saline, hypertonic saline and hypertonic saline colloid
      resuscitation fluids in an infant animal model of hypovolemic shock.
AB  - PURPOSE: Incorrect resuscitation after hypovolemic shock is a major contributor
      to preventable pediatric death. Several studies have demonstrated that small
      volumes of hypertonic or hypertonic-hyperoncotic saline can be an effective
      initial resuscitation solution. However, there are no pediatric studies to
      recommend their use. The aim of this study is to determine if in an infant animal
      model of hemorrhagic shock, the use of hypertonic fluids, as opposed to isotonic
      crystalloids, would improve global hemodynamic and perfusion parameters. METHODS:
      Experimental, randomized animal study including thirty-four 2-to-3-month-old
      piglets. 30 min after controlled 30 mL kg(-1) bleed, pigs were randomized to
      receive either normal saline (NS) 30 mL kg(-1) (n=11), 3% hypertonic saline (HS)
      15 mL kg(-1) (n=12), or 5% albumin plus 3% hypertonic saline (AHS) 15 mL kg(-1)
      (n=11). RESULTS: High baseline heart rate (HR) and low mean arterial pressure
      (MAP), cardiac index (CI), brain tissue oxygenation index (bTOI), and lactate
      were recorded 30 min after volume withdrawal, with no significant differences
      between groups. Thirty minutes after volume replacement there were no significant
      differences between groups for HR (NS, 188+/-14; HS, 184+/-14; AHS, 151+/-14
      bpm); MAP (NS, 80+/-7; HS, 86+/-7; AHS, 87+/-7 mmHg); CI (NS, 4.1+/-0.4; HS,
      3.9+/-0.4; AHS, 5.1+/-0.4 mL min(-1)m(-2)); lactate (NS, 2.8+/-0.7; HS, 2.3+/
      0.6; AHS, 2.4+/-0.6 mmol L(-1)); bTOI (NS, 43.9+/-2.2; HS, 40.1+/-2.5; AHS,
      46.1+/-2.3%). CONCLUSIONS: In this model of hypovolemic shock, hypertonic fluids
      achieved similar end-points as twice the volume of NS. Animals treated with
      albumin plus hypertonic saline presented prolonged increase in blood volume
      parameters and recovery of the oxygen debt.

PMID- 22387922
TI  - Survey of vaccine beliefs and practices among families affected by autism
      spectrum disorders.

PMID- 22387923
TI  - Addressing families' unmet social needs within pediatric primary care: the health
      leads model.

PMID- 22387924
TI  - Monkey bites: case report and literature review.

PMID- 22387925
TI  - Adrenal insufficiency and growth failure secondary to inhaled corticosteroids: a
      paradoxical complication.

PMID- 22387926
TI  - Bruising, tingling, and numbness in a pale adolescent.

PMID- 22387928
TI  - Fear conditioning in psychopaths: event-related potentials and peripheral
      measures.
AB  - Aversive pavlovian delay conditioning was investigated in a sample of 11 criminal
      psychopaths as identified by using the Psychopathy Checklist-Revised and 11
      matched healthy controls. A painful electric stimulus served as unconditioned
      stimulus and neutral faces as conditioned stimuli. Event-related potentials,
      startle response potentiation, skin conductance response, corrugator activity,
      and heart rate were assessed, along with valence, arousal, and contingency
      ratings of the CS and US. Compared to healthy controls, psychopathic subjects
      failed to differentiate between the CS+/CS- as shown by an absence of a
      conditioned response in startle potentiation and skin conductance measures.
      Through use of a fear-eliciting US, these data confirm previous findings of a
      deficient capacity to form associations between neutral and aversive events in
      psychopathy that appears unrelated to cognitive deficits and is consistent with
      hypothesized frontolimbic deficits in the disorder.

PMID- 22387927
TI  - Tristetraprolin: roles in cancer and senescence.
AB  - Cancer and senescence are both complex transformative processes that dramatically
      alter many features of cell physiology and their interactions with surrounding
      tissues. Developing the wide range of cellular features characteristic of these
      conditions requires profound alterations in global gene expression patterns,
      which can be achieved by suppressing, activating, or uncoupling cellular gene
      regulatory pathways. Many genes associated with the initiation and development of
      tumors are regulated at the level of mRNA decay, frequently through the activity
      of AU-rich mRNA-destabilizing elements (AREs) located in their 3'-untranslated
      regions. As such, cellular factors that recognize and control the decay of ARE
      containing mRNAs can influence tumorigenic or senescent phenotypes mediated by
      products of these transcripts. In this review, we discuss evidence showing how
      suppressed expression and/or activity of the ARE-binding protein tristetraprolin
      (TTP) can contribute to these processes. Next, we outline current findings
      linking TTP suppression to exacerbation of individual tumorigenic phenotypes, and
      the roles of specific TTP substrate mRNAs in mediating these effects. Finally, we
      survey potential mechanisms that cells may employ to suppress TTP expression in
      cancer, and propose potential diagnostic and therapeutic strategies that may
      exploit the relationship between TTP expression and tumor progression or
      senescence.

PMID- 22387934
TI  - New pi-arene ruthenium(II) piano-stool complexes with nitrogen ligands.
AB  - The synthesis, characterization, DNA interaction and antiproliferative behavior
      of new pi-arene ruthenium(II) piano-stool complexes with nitrogen ligands are
      described. Three series of organometallic compounds of formulae [RuCl(2)(eta(6)-p
      cym)L] were synthesized (with L=2-, 3- or 4-methylpyridine; L=2,3-, 2,4-, 2,5-,
      3,4-, 3,5-dimethylpyridine and L=1,2-, 1,3- 1,4-methylaminobenzene). The crystal
      structures of [RuCl(2)(p-cym)(4-methylpyridine)], [RuCl(2)(p-cym)(3,4
      dimethylpyridine)] and [RuCl(2)(p-cym)(1,4-methylaminobenzene)] were resolved and
      the characterization was completed by spectroscopic UV-vis, FT-IR and (1)H NMR
      studies. Electrochemical experiments were performed by cyclic voltammetry to
      estimate the redox potential of the Ru(II)/Ru(III) couple. The interaction with
      plasmid pBR322 DNA was studied through the examination of the electrophoretical
      mobility and atomic force microscopy, and interaction with ct-DNA by circular
      dichroism, viscosity measurements and fluorescence studies based on the DNA
      ethidium bromide complex. The antiproliferative behavior of the series with
      L=methylpyridine was assayed against two tumor cell lines, i.e. LoVo and MiaPaca.
      The results revealed a moderate cytotoxicity with a higher activity for the LoVo
      cell line compared to the MiaPaca one.

PMID- 22387929
TI  - A heartfelt response: Oxytocin effects on response to social stress in men and
      women.
AB  - BACKGROUND: Animal research indicates that oxytocin is involved in social
      behavior, stress regulation, and positive physiologic adaptation. This study
      examines whether oxytocin enhances adaptive responses to social stress and
      compares effects between men and women. METHODS: Hypotheses were tested with a
      placebo-controlled, double-blind experiment. Social stress was induced. Changes
      in cardiovascular reactivity, affect, and behavior were assessed. RESULTS:
      Participants given oxytocin, relative to placebo, responded to social stress with
      a challenge orientation characterized by a benign pattern of cardiovascular
      reactivity. Gender differences emerged. Men given oxytocin reported less negative
      affect and had greater vagal rebound, while women given oxytocin reported more
      anger and had better math performance following social stress. DISCUSSION:
      Findings indicate oxytocin stimulates an approach-oriented cardiovascular profile
      during social stress, suggesting mechanisms by which oxytocin might improve
      physical health. However, before considering oxytocin as therapeutic or uniformly
      enhancing health, greater understanding of possible gender differences in effects
      is needed.

PMID- 22387936
TI  - Validation of food diaries as measures of dietary behaviour change.
AB  - This study aimed to validate the ability of a 24-h food diary (the DIET-24) to
      accurately detect change in children's fruit and vegetable consumption at school
      snack time following implementation of the Food Dudes healthy eating
      intervention. Participants were 4- to 9-year-old children from two primary
      schools in England. There were 148 participants in the intervention school and 43
      participants in the no intervention control school. For each child, snack-time
      fruit and vegetable consumption was measured separately by weight (grammes), and
      compared with teachers' estimates (to the nearest half portion) using the DIET
      24. Both consumption measures were taken at T1 (pre-intervention) and T2 (post
      intervention). At each time-point, Spearman rank correlations between the two
      measures were low to moderate, but significant. However, when compared with
      weighed measures, the DIET-24 did not always accurately detect significant
      changes in children's fruit and vegetable consumption following the intervention.
      To provide sensitive measures of behaviour change, it is important that dietary
      measures assess as accurately as possible the amount of food consumed, rather
      than, as is often the case, rely on all-or-none portion estimates. This issue is
      important for the establishment of a reliable evidence-base for healthy eating
      interventions.

PMID- 22387937
TI  - Coupling exo- and endocytosis: an essential role for PIP2 at the synapse.
AB  - Chemical synapses are specialist points of contact between two neurons, where
      information transfer takes place. Communication occurs through the release of
      neurotransmitter substances from small synaptic vesicles in the presynaptic
      terminal, which fuse with the presynaptic plasma membrane in response to neuronal
      stimulation. However, as neurons in the central nervous system typically only
      possess ~200 vesicles, high levels of release would quickly lead to a depletion
      in the number of vesicles, as well as leading to an increase in the area of the
      presynaptic plasma membrane (and possible misalignment with postsynaptic
      structures). Hence, synaptic vesicle fusion is tightly coupled to a local
      recycling of synaptic vesicles. For a long time, however, the exact molecular
      mechanisms coupling fusion and subsequent recycling remained unclear. Recent work
      now indicates a unique role for the plasma membrane lipid phosphatidylinositol
      4,5-bisphosphate (PIP(2)), acting together with the vesicular protein
      synaptotagmin, in coupling these two processes. In this work, we review the
      evidence for such a mechanism and discuss both the possible advantages and
      disadvantages for vesicle recycling (and hence signal transduction) in the
      nervous system. This article is part of a Special Issue entitled Lipids and
      Vesicular Transport.

PMID- 22387938
TI  - Real-time UV imaging of piroxicam diffusion and distribution from oil solutions
      into gels mimicking the subcutaneous matrix.
AB  - A novel real-time UV imaging approach for non-intrusive investigation of the
      diffusion and partitioning phenomena occurring during piroxicam release from
      medium chain triglyceride (MCT) solution into two hydrogel matrices is described.
      Two binary polymer/buffer gel matrices, 0.5% (w/v) agarose and 25% (w/v) Pluronic
      F127, were applied as simple models mimicking the subcutaneous tissue. The
      evolution of the absorbance maps as a function of time provided detailed
      information on the piroxicam release processes upon the exposure of the gel
      matrices to MCT. Using calibration curves, the concentration maps of piroxicam in
      the UV imaging area were determined. Regression of the longitudinal concentration
      distance profiles, which were obtained using expressions derived from Fick's
      second law, provided the diffusivity and the distribution coefficients of
      piroxicam penetrated into the gels. The obtained MCT-agarose (pH 7.4)
      distribution coefficient of 1.4 was identical to the MCT-aqueous (pH 7.4)
      distribution coefficient determined by the shake-flask method whereas that of the
      MCT-Pluronic F127 system was four times less. The experimental data show that UV
      imaging may have considerable potential for investigating the transport
      properties of drug formulations intended for the subcutaneous administration.

PMID- 22387947
TI  - The uterus under hormonal control--cycling for life.

PMID- 22387948
TI  - Further characterization of the juxtaglomerular neurons in the mouse main
      olfactory bulb by transcription factors, Sp8 and Tbx21.
AB  - Juxtaglomerular neurons in the mouse main olfactory bulb consist of various types
      of neurons, especially classified by their chemical properties such as
      transmitter-related molecules and calcium binding proteins. In addition several
      transcription factors have been revealed to characterize neuronal subpopulations.
      In this study we examined the immunoreactivities of two transcription factors,
      Sp8 and Tbx21, in the juxtaglomerular neuronal subpopulations containing
      calretinin, calbindin, secretagogin, tyrosine hydroxylase (TH) and nitric oxide
      synthase (NOS). Both Sp8 and Tbx21 immunoreactivities were so diverse in their
      staining intensities. Almost all calretinin and secretagogin positive neurons
      were relatively strongly Sp8 positive, whereas none of calbindin positive neurons
      were Sp8 positive. TH positive neurons were also usually Sp8 positive, although
      some were faintly positive. These four types of interneurons were Tbx21 negative.
      On the other hand large faintly NOS positive external tufted cells were
      occasionally Tbx21 positive but always Sp8 negative, whereas small NOS positive
      periglomerular cells without distinctly stained dendrites were usually Sp8
      positive and Tbx21 negative. Strangely, most of strongly NOS positive
      periglomerular cells with distinctly stained dendritic processes were Sp8
      negative and Tbx21 negative. Thus Sp8 and Tbx21 immunoreactivities further
      characterized juxtaglomerular neurons and, especially confirmed the heterogeneity
      of NOS positive juxtaglomerular neurons.

PMID- 22387966
TI  - Genetic variation in the VP7 gene of rotavirus G1P[8] strains isolated in
      Vietnam, 1998-2009.
AB  - Group A rotavirus genotype G1P[8] is the most common strain affecting humans
      around the world over the past few decades. In this study, we examined genetic
      variation in the VP7 gene of rotavirus G1P[8] strains, detected in children of
      four major cities of Vietnam during three different rotavirus seasons: 1998-1999,
      2007-2008 and 2008-2009 in order to assess the evolution of the virus over 11
      years. Fecal samples (n=73) from children hospitalized for gastroenteritis caused
      by G1P[8] rotavirus were analyzed by DNA sequencing of gene 9 encoding the VP7
      capsid protein. Phylogenetic analyses indicated that VP7 gene of the G1 strains
      from 1999 contained a lineage I, while rotaviruses from 2009 clustered in lineage
      II. Both of these lineages were found co-circulating in 2007-2008 season. While
      different sublineages of lineage I and II co-circulated in the 1998-1999 and 2007
      2008 seasons, almost all strains in 2009 belonged to sub-lineage II-C. In the
      analysis using selected 10 strains, the VP4 genes of these 2 VP7-G1 lineages were
      all grouped in F45-like cluster. Deduced amino acid analyses indicated that there
      were thirteen amino acid substitutions between strains of two lineages. Of those,
      two were found in antigenic regions A and C, implying possible antigenic
      differences between these two lineages. The G1P[8] strains in Vietnam are very
      genetically diverse and dynamic, implying the frequent monitoring on evolution of
      rotavirus will be important to assess efficacy of rotavirus vaccine in Vietnam.

PMID- 22387967
TI  - Abalone viral ganglioneuritis: establishment and use of an experimental immersion
      challenge system for the study of abalone herpes virus infections in Australian
      abalone.
AB  - In late 2005, acute mortalities occurred in abalone on farms located in Victoria,
      Australia. Disease was associated with infection by an abalone herpes virus
      (AbHV). Subsequently, starting in 2006, the disease (abalone viral
      ganglioneuritis; AVG) was discovered in wild abalone in Victorian open waters.
      Currently, it continues to spread, albeit at a slow rate, along the Victorian
      coast-line. Here, we report on experimental transmission trials that were carried
      out by immersion using water into which diseased abalone had shed infectious
      viral particles. At various time points following exposure, naive abalone were
      assessed by an AbHV-specific real-time PCR and histological analyses including in
      situ hybridization (ISH). Results demonstrated that while exposed abalone began
      displaying clinical signs of the disease from 60 hours post exposure (hpe), they
      tested positive for the presence of viral DNA at 36 hpe. Of further interest, the
      AbHV DNA probe used in the ISH assay detected the virus as early as 48 hpe.

PMID- 22387968
TI  - Continuous computation in engineered gene circuits.
AB  - In this paper we consider the problem of representation and measurement in
      genetic circuits, and investigate how they can affect the reliability of
      engineered systems. We propose a design scheme, based on the notion of continuous
      computation, which addresses these issues. We illustrate the methodology by
      showing how a concept from computer architecture (namely, branch prediction) may
      be implemented in vivo, using a distributed approach. Simulation results confirm
      the in-principle feasibility of our method, and offer valuable insights into its
      future laboratory validation.

PMID- 22387969
TI  - Institutionalizing integrated treatment for concurrent disorders: creating new
      organizational discourse.
AB  - BACKGROUND: The high overlap of mental health and substance use problems in the
      Canadian health care system and the subsequent demand for more effective services
      for clients with these high-risk issues have stimulated the debate on their
      integrated treatment. Although the idea of integration has been endorsed by
      decision makers at both programs and system levels, little attention has been
      paid to factors that have facilitated this process. PURPOSE: In this article, the
      processes by which organizational texts, language, metaphors, and symbols have
      facilitated institutionalization of integrated treatment are identified and
      discussed. METHODOLOGY/APPROACH: Findings from a qualitative case study of 2
      treatment programs that were part of a large, urban hospital in Ontario providing
      services for populations with concurrent disorders are presented. Data were
      collected using semistructured interviews with professionals and clients,
      analysis of policy and organizational documents, and nonparticipant observations.
      FINDINGS: Research evidence on comorbidity, government reports, and other
      organizational texts that were created and disseminated across the province has
      contributed to the dissemination of the concept of integration. Certain ideas
      might be successfully implemented when environments are conducive to change; such
      environmental catalysts include the status of professionals who support new
      discourse, the characteristics and importance of the problem being addressed, and
      the timing of implementation. The findings clearly demonstrate that the
      conditions of the wider institutional environment-the emergence of research
      evidence on comorbidity and the provincial health care reform, with its focus on
      rationalizing the existing health care system-supported the idea of integration.
      PRACTICE IMPLICATIONS: The ability to understand how discursive activities of
      program planners, clinicians, and policy makers contribute to making new ideas
      deeply embedded in organizational structures can become an important mechanism of
      effective decision-making activities when health managers attempt to promote new
      plans and strategies.

PMID- 22387970
TI  - Understanding patient e-loyalty toward online health care services.
AB  - BACKGROUND: Public health institutions are making a great effort to develop
      patient-targeted online services in an attempt to enhance their effectiveness and
      reduce expenses. However, if patients do not use those services regularly, public
      health institutions will have wasted their limited resources. Hence, patients'
      electronic loyalty (e-loyalty) is essential for the success of online health care
      services. PURPOSES: In this research, an extended Technology Acceptance Model was
      developed to test e-loyalty intent toward online health care services offered by
      public health institutions. METHODOLOGY: Data from a survey of 256 users of
      online health care services provided by the public sanitary system of a region in
      Spain were analyzed. The research model was tested by using the structural
      equation modeling approach. FINDINGS: The results obtained suggest that the core
      constructs of the Technology Acceptance Model (perceived usefulness, ease of use,
      and attitude) significantly affected users' behavioral intentions (i.e., e
      loyalty intent), with perceived usefulness being the most decisive antecedent of
      affective variables (i.e., attitude and satisfaction). This study also reveals a
      general support for patient satisfaction as a determinant of e-loyalty intent in
      online health care services. IMPLICATIONS: Policy makers should focus on striving
      to get the highest positive attitude in users by enhancing easiness of use and,
      mainly, perceived usefulness. Because through satisfaction of patients, public
      hospitals will enlarge their patient e-loyalty intent, health care providers must
      always work at obtaining satisfied users and to encourage them to continue using
      the online services.

PMID- 22387971
TI  - Dynamics of hospital competition: social network analysis in the Italian National
      Health Service.
AB  - BACKGROUND: In the early 1990s, the governments of many countries took the first
      steps toward introducing market forces into the provision of health care
      services, with the aim of increasing hospital efficiency and quality of care.
      Several reforms have been developed to strengthen the role of competition, giving
      rise to forms of "managed competition." As a result, the environment in which
      providers operate and perform is increasingly characterized by conditions of
      competition, rather than of cooperation. PURPOSE: The aim of this study was to
      analyze the evolution of competitive interdependences among hospitals and the
      impact of organizational demographics on pair-wise competition. METHODOLOGY:
      Longitudinal data on competitive interdependences collected within a regional
      community of hospital organizations in the Italian National Health Service were
      analyzed. Stochastic actor-based models designed for estimating network dynamics
      were used to study organizational characteristics influencing patterns of change
      in competitive interdependences. FINDINGS: The results indicated that
      interorganizational cooperation is a significant predictor of competitive
      interdependences, that pair-wise competition among hospitals is primarily local,
      and that competitive interdependences are more likely to occur between local
      providers that differed with respect to performance and volume of activity.
      PRACTICE IMPLICATIONS: Exploring the evolution of competitive interdependences
      between hospitals is salient for administrators who are interested in increasing
      their understanding of the whole market. They can better identify direct
      competitors by paying particular attention to those organizational
      characteristics that likely predict competitive actions. This approach is also
      important for policy makers, which may be interested in better targeting hospital
      restructuring interventions while implementing procompetition reforms.

PMID- 22387972
TI  - Updated assessment of the prevalence, spectrum and case definition of autoimmune
      disease.
AB  - Autoimmune diseases are heterogeneous with regard to prevalence, manifestations,
      and pathogenesis. The classification of autoimmune diseases has varied over time.
      Here, we have compiled a comprehensive up-to-date list of the autoimmune
      diseases, and have reviewed published literature to estimate their prevalence. We
      identified 81 autoimmune diseases. The overall estimated prevalence is 4.5%, with
      2.7% for males and 6.4% for females. For specific diseases, prevalence ranges
      from 1% to <1/10(6). Considering all diseases in the class, the most common mean
      age-of-onset was 40-50 years. This list of autoimmune diseases has also yielded
      information about autoantigens. Forty-five autoimmune diseases have been
      associated with well-defined autoantigens. Of the diseases with known
      autoantigens, 33.3% had highly repetitive sequences, 35.6% had coiled-coil
      arrangements and 57.8% were associated with cellular membranes, which means that
      based on these structural motifs alone, autoantigens do not appear to be a random
      sample of the human proteome. Finally, we identified 19 autoimmune diseases that
      phenocopy diseases arising from germline mutations in the corresponding
      autoantigen. Collectively, our findings lead to a tentative proposal for criteria
      for assigning autoimmune pathogenesis to a particular disease.

PMID- 22387973
TI  - Antinuclear antibody detection by automated multiplex immunoassay in untreated
      patients at the time of diagnosis.
AB  - Fully automated multiplex immunoassays are increasingly used as first line
      screening for antinuclear antibodies. The diagnostic performance of such
      multiplex assays in untreated patients at the time of diagnosis has not been
      reported. Antinuclear antibodies were measured by indirect immunofluorescence
      (IIF) (dilution 1:160) and by BioPlex 2200 ANA screen (antibodies to dsDNA,
      chromatin, ribosomal protein, SSA-52, SSA-60, SSB, Sm, SmRNP, RNP-A, RNP-68, Scl
      70, Jo-1, and centromere B) in 236 patients with a systemic rheumatic disease at
      the time of diagnosis, 149 blood donors, 139 patients with chronic fatigue
      syndrome (CFS), and 134 diseased controls. BioPlex ANA screen and IIF were
      positive in, respectively, 79% and 90% of patients with systemic lupus
      erythematosus (SLE), 60% and 60% with cutaneous lupus, 72% and 93% with systemic
      sclerosis (SSc), 100% and 100% with mixed connective tissue disease (MCTD), 89%
      and 56% with primary Sjogren's (SS) syndrome, 36% and 36% with
      polymyositis/dermatomyositis, 5.4% and 6% of blood donors, 7.2% and 3.6% of
      patients with CFS, and 11% and 18% of diseased controls. BioPlex test result
      interval specific likelihood ratios increased with increasing antibody
      concentration. The simultaneous presence of at least three antibodies by BioPlex
      was found in 35% of patients with SLE, 4% with SSc, 100% with MCTD, 64% with SS,
      7% with inflammatory myopathy, 0.7% of CFS and diseased controls, and none of the
      blood donors. In conclusion, test result specific likelihood ratios and the
      presence of multiple autoantibodies help with the interpretation of data
      generated by multiplex immunoassays.

PMID- 22387974
TI  - Transfer of natural radionuclides from hay and silage to cow's milk in the
      vicinity of a former uranium mine.
AB  - After the closure of the former Zirovski Vrh uranium mine in Slovenia, mining and
      milling wastes were deposited on two waste piles, which are located close to the
      mine. These wastes contain elevated levels of natural radionuclides from the
      uranium decay chain. Due to different migration processes (erosion, aerial
      deposition, through groundwater), these radionuclides can be transported via
      fodder into cow's milk, which is an important foodstuff for Slovenian people.
      Therefore, natural radionuclides were analysed in the transfer food chain from
      soil to cow's fodder and cow's milk. After sampling, (238)U, (234)U, (230)Th,
      (226)Ra, (210)Pb and (210)Po were determined using radiochemical separation
      methods and alpha spectrometry or proportional counting. Hay and silage to milk
      concentration ratios (kg dry weight L(-1)) were calculated and were 0.260 for
      (238)U, 0.255 for (230)Th, 0.070 for (226)Ra, 0.021 for (210)Pb and 0.019 for
      (210)Po. The calculated annual ingestion dose due to milk consumption for the
      natural radionuclides analysed was 9 MUSv/year for adults and 389 MUSv/year for
      infants with the highest contribution of (210)Po (51% for adults and 63% for
      infants) and (210)Pb (36% for adults and 24% for infants). This study provides
      new data quantifying the transfer of natural radionuclides to milk, which is a
      parameter for which there have been very few previously reported values.

PMID- 22387979
TI  - A 5-year retrospective study of survival of zirconia single crowns fitted in a
      private clinical setting.
AB  - OBJECTIVES: The aim of this report was to evaluate the 5-year clinical
      performance and survival of zirconia (NobelProceraTM) single crowns. METHODS: All
      patients treated with porcelain-veneered zirconia single crowns in a private
      practice during the period October 2004 to November 2005 were included. The
      records were scrutinized for clinical data. Information was available for 162
      patients and 205 crowns. RESULTS: Most crowns (78%) were placed on premolars and
      molars. Out of the 143 crowns that were followed for 5 years, 126 (88%) did not
      have any complications. Of those with complications, the most common were:
      extraction of abutment tooth (7; 3%), loss of retention (15; 7%), need of
      endodontic treatment (9; 4%) and porcelain veneer fracture (6; 3%). No zirconia
      cores fractured. In total 19 restorations (9%) were recorded as failures:
      abutment tooth extraction (7), remake of crown due to lost retention (6), veneer
      fracture (4), persistent pain (1) and caries (1). The 5-year cumulative survival
      rate (CSR) was 88.8%. CONCLUSIONS: According to the present 5-year results
      zirconia crowns (NobelProceraTM) are a promising prosthodontic alternative also
      in the premolar and molar regions. Out of the 143 crowns followed for 5 years,
      126 (88%) did not have any complications. However, 9% of the restorations were
      judged as failures. Further studies are necessary to evaluate the long-term
      success.

PMID- 22387981
TI  - Exposure of perfluorononanoic acid suppresses the hepatic insulin signal pathway
      and increases serum glucose in rats.
AB  - Exposure to perfluorononanoic acid (PFNA), an increasingly persistent organic
      pollutant that has been detected in abiotic and biotic matrices, has been
      demonstrated to cause hepatotoxicity in animals. However, the effects of PFNA on
      hepatic glucose metabolism have not been fully characterized. In this study, male
      rats were exposed to 0, 0.2, 1 or 5mg/kg/d PFNA for 14 days to explore the
      specific effect of PFNA on hepatic glycometabolism and its underlying mechanisms.
      The results showed that administration of 5mg/kg/d PFNA significantly increased
      serum glucose and hepatic glycogen in rats. Quantitative real-time PCR analysis
      showed that PFNA exposure changed the expression levels of several genes related
      to hepatic glucose metabolism, such as the glucose-6-phosphatase (G6PC) gene and
      the glucose transporter 2 (GLUT2) gene, which were upregulated, and the
      glucokinase (GCK) gene and the phosphoinositide-3-kinase, catalytic, alpha
      polypeptide (PI3Kca) gene, which were decreased. The protein expression levels of
      phospho-insulin receptor 1(IRS1), phospho-PI3K, phospho-AKT and phospho
      phosphoinositide-dependent kinase 1 (PDK1) were decreased in the livers of rats
      that received 5mg/kg/d PFNA. The expression of phospho-glycogen synthase kinase-3
      beta (GSK3beta, Ser 9) was increased, which explains the augment of hepatic
      glycogen. Significant increases in hydrogen peroxide (H(2)O(2)) and
      malondialdehyde (MDA) were found in the livers of 5mg/kg/d PFNA-treated rats.
      Thus, exposure to PFNA disordered glucose metabolism via inhibiting hepatic
      insulin signal pathway, accelerating the output of glucose and increasing
      glycogen synthesis in the rat liver. Furthermore, the oxidative stress induced by
      PFNA may be involved in this process.

PMID- 22387982
TI  - High-performance metabolic profiling of plasma from seven mammalian species for
      simultaneous environmental chemical surveillance and bioeffect monitoring.
AB  - High-performance metabolic profiling (HPMP) by Fourier-transform mass
      spectrometry coupled to liquid chromatography gives relative quantification of
      thousands of chemicals in biologic samples but has had little development for use
      in toxicology research. In principle, the approach could be useful to detect
      complex metabolic response patterns to toxicologic exposures and to detect
      unusual abundances or patterns of potentially toxic chemicals. As an initial
      study to develop these possible uses, we applied HPMP and bioinformatics analysis
      to plasma of humans, rhesus macaques, marmosets, pigs, sheep, rats and mice to
      determine: (1) whether more chemicals are detected in humans living in a less
      controlled environment than captive species and (2) whether a subset of plasma
      chemicals with similar inter-species and intra-species variation could be
      identified for use in comparative toxicology. Results show that the number of
      chemicals detected was similar in humans (3221) and other species (range 2537
      3373). Metabolite patterns were most similar within species and separated samples
      according to family and order. A total of 1485 chemicals were common to all
      species; 37% of these matched chemicals in human metabolomic databases and
      included chemicals in 137 out of 146 human metabolic pathways. Probability-based
      modularity clustering separated 644 chemicals, including many endogenous
      metabolites, with inter-species variation similar to intra-species variation. The
      remaining chemicals had greater inter-species variation and included
      environmental chemicals as well as GSH and methionine. Together, the data suggest
      that HPMP provides a platform that can be useful within human populations and
      controlled animal studies to simultaneously evaluate environmental exposures and
      biological responses to such exposures.

PMID- 22387984
TI  - Thyrotropic activity of recombinant human glycoprotein hormone analogs and
      pituitary mammalian gonadotropins in goldfish (Carassius auratus): insights into
      the evolution of thyrotropin receptor specificity.
AB  - Thyrotropin (TSH) is a pituitary glycoprotein hormone heterodimer that binds to
      its G-protein coupled receptor (TSH-R) at the thyroid to promote the synthesis
      and secretion of thyroid hormone. Very little is known about TSH-TSH-R
      interactions in teleost fish. Mammalian gonadotropins have been reported to have
      an intrinsic ability to activate teleost fish TSH-Rs, suggesting the TSH-R in
      teleost fish is more promiscuous than in other vertebrates. In this study we
      utilized the goldfish T(4)-release response and recombinant human TSH analogs as
      in vivo tools to evaluate the structural constraints on hormone-receptor
      interactions. We found that four positively charged lysines substituted for
      neutral or negatively charged amino acids within positions 11-20 of the
      glycoprotein hormone subunit alpha (GSUalpha) significantly increased biological
      activity of hTSH in fish, as it does in mammals. We further found that bovine
      follicle stimulating hormone but not luteinizing hormone, whose GSUalpha subunits
      also contain four lysine or arginine amino acid residues in the N-terminal
      portion of GSUalpha, was thyrotropic in goldfish, suggesting gonadotropin beta
      subunit contributes to the heterothyrotropic activity. Though recombinant human
      FSH did not produce a dose-dependent increase in T(4), thyrotropic activity could
      be acquired with the addition of positively charged amino acids at the N-terminal
      portion of its GSUalpha, confirming the importance of the charge on those amino
      acids for activation of the goldfish TSH-R. These studies demonstrate that
      mammalian glycoprotein hormone analogs can be utilized to evaluate the
      conservation of receptor binding and activation mechanisms between fish and
      mammals.

PMID- 22387985
TI  - The influence of social subordinate housing on the withdrawal effects from
      progesterone and estradiol in male rats.
AB  - Chronic stress and its concomitant neurobiological consequences are, in all
      probability, provocateurs of mental disease in humans. To gain some insight into
      the provocative effects of stress on hormonally dependent conditions, we
      developed a rat model that combines social subordinate housing (SSH) with
      withdrawal from combined progesterone (P) and estradiol (E) treatment (PEWD). At
      the start of the experiment, male Wistar rats were housed in triads consisting of
      one younger rat (35 days old) and two older rats (55 days old), with the intent
      of producing subordination stress in the younger animals. Triads containing three
      35-day-old rats were used as age controls. Subordination stress was assessed with
      the elevated plus maze (EPM) and by corticosterone (CORT) analysis. Social rank
      within the triads was determined using a food competition test (FCT) and a tube
      test (TT). The younger rats (subordinate) and the dominant rats were assigned to
      10 days of treatment with 5mg/kg P combined with 10 MUg/kg E, or placebo
      (vehicle). Twenty-four hours after the last injection, the subordinate and
      dominant animals were tested in an open-field test (OFT) and a social challenge
      test (SCT). The SCT consisted of a 10-min exposure to three unfamiliar rats. SSH
      increased baseline CORT levels and reduced EPM open-arm time and post-EPM CORT
      levels compared to age-control rats. Only in the subordinate animals did PEWD
      increase locomotor activity and digging behavior, and reduce wrestling and
      pinning behavior. The behavioral results indicate an interaction between the
      effects of the lasting social subordinate stress and PEWD.

PMID- 22387986
TI  - Diagnosing pregnancy in free-ranging dugongs using fecal progesterone metabolite
      concentrations and body morphometrics: a population application.
AB  - Assessing reproductive status and monitoring reproductive rates is important in
      the effective management of vulnerable marine mammal species such as the dugong
      (Dugong dugon). Knowledge of the reproductive physiology of this species is
      limited, and determining reproductive parameters (e.g., sexual maturation,
      pregnancy, and reproductive senescence) has been restricted by a lack of non
      lethal methods for assessing reproductive status in free-ranging individuals. The
      aim of this study was to develop a method to identify pregnant individuals in a
      wild dugong population. Using an enzymeimmunoassay, we quantified concentrations
      of fecal progesterone metabolites (fP) in 322 dugongs, including confirmed
      pregnant females (n=10), presumed non-pregnant adult females (n=25), juvenile
      females (n=24), subadult females (n=41), adult females of unknown pregnancy state
      (n=63), and males of all sizes (n=159). External body morphometrics of each
      dugong were measured, and confirmation of pregnancy in adult female dugongs was
      determined by ultrasonography or observation of subsequent neonates.
      Concentrations of fP were different between sexes and reproductive size classes
      (P<0.001), and ~30-fold higher in confirmed pregnant dugongs (2017-7760 ng/g)
      compared to presumed non-pregnant females (30-221 ng/g), juvenile females (29-195
      ng/g), and males (24-261 ng/g) (P<0.001). Body measures of maximum and anal
      girths, and teat length were all greater in confirmed pregnant females than
      presumed non-pregnant females (all P<0.05). We evaluated a Discriminant Function
      Analysis (DFA) to provide a model for predicting pregnant and non-pregnant
      dugongs. Cross-validated results showed that the DFA correctly classified 100% of
      pregnant and non-pregnant females using fP concentrations, body length, fineness
      ratio (an index of body shape), and teat length (a female reproductive trait).
      Using the DFA model, we classified the pregnancy status of all female dugongs and
      identified a total of 30 females as pregnant and 133 females as non-pregnant from
      the sampled population over the sample period. Pregnant dugongs in the Moreton
      Bay population are characterized by fecal progesterone metabolite concentrations
      > 1000 ng/g, body length >= 260 cm, maximum girth >= 215 cm, anal girth >= 126
      cm, and teat length >= 5 cm long. In summary, analysis of fP concentrations in
      combination with body morphometrics may be used to diagnose pregnancy in free
      ranging dugongs, and provides a new tool to monitor breeding rates of wild
      sirenian populations.

PMID- 22387987
TI  - Seasonal changes in plasma steroid levels in relation to ovarian steroidogenic
      ultrastructural features and progesterone receptors in the house gecko,
      Hemidactylus flaviviridis, in Oman.
AB  - A comprehensive study of the annual ovarian cycle in the house gecko,
      Hemidactylus flaviviridis, was conducted in Oman. Circulating estradiol (E(2)),
      progesterone (P), and testosterone (T) were measured during the active and
      inactive phases of the cycle. The steroid levels were related to the
      steroidogenic ultrastructural features such as the abundance of smooth
      endoplasmic reticulum (SER), the presence of cisternal whorls, and close
      association of lipid droplets with swollen vesiculated mitochondria and SER. The
      steroids were measured using a sensitive detection technique HPLC-MS/MS. E(2)
      levels began to rise in January at the onset of vitellogenesis and continued to
      rise between February and May relative to ovulation, postovulation, gravidity and
      oviposition. Afterwards, E(2) remained low during the inactive phase (June
      December). P levels increased significantly in March and peaked in April, which
      coincided with luteinization. P levels began to decline relative to luteolysis
      (May-June). Afterwards, it remained low throughout the inactive phase. T levels
      rose significantly in March-April coinciding with vitellogenesis, but decreased
      rapidly and significantly in May and remained low during the inactive phase.
      Progesterone receptors (PR), identified using immunohistochemistry, were strongly
      expressed during the breeding period, but were absent during the non-breeding
      period. The appearance of the steroidogenic ultrastructural features in the
      preovulatory and lutein granulosa cells was correlated with the significant rise
      in the three steroid levels and the PR. As the steroid levels declined, the
      granulosa cells underwent a general degeneration and disruption of the associated
      steroidogenic features.

PMID- 22387988
TI  - Combined inhibition of EGFR and CK2 augments the attenuation of PI3K-Akt-mTOR
      signaling and the killing of cancer cells.
AB  - Ser/Thr protein kinase CK2 regulates multiple processes that play important roles
      in the sensitivity of cancer to epidermal growth factor receptor targeting
      therapeutics, including PI3K-Akt-mTOR signaling, Hsp90 activity, and inhibition
      of apoptosis. We hypothesized that top-down inhibition of EGFR, combined with
      lateral suppression of multiple oncogenic pathways by targeting CK2, would create
      a pharmacologic synthetic lethal event and result in an improved cancer therapy
      compared to EGFR inhibition alone. This hypothesis was tested by combining CX
      4945, a first-in-class clinical stage inhibitor of CK2, with the EGFR tyrosine
      kinase inhibitor, erlotinib, in vitro and in vivo in models of non-small cell
      lung carcinoma, NCI-H2170, and squamous cell carcinoma, A431. Our results
      demonstrate that combination of CX-4945 with erlotinib results in enhanced
      attenuation of the PI3K-Akt-mTOR pathway. We also observed an increase in
      apoptosis, synergistic killing of cancer cells in vitro, as well as improved
      antitumor efficacy in vivo. Taken together, these data position CK2 as a valid
      pharmacologic target for drug combinations and support further evaluation of CX
      4945 in combination with EGFR targeting agents.

PMID- 22387989
TI  - Pan-colonic field defects are detected by CGH in the colons of UC patients with
      dysplasia/cancer.
AB  - BAC arrays were used to evaluate genomic instability along the colon of patients
      with ulcerative colitis (UC). Genomic instability increases with disease
      progression and biopsies more proximal to dysplasia showed increased instability.
      Pan-colonic field copy number gain or loss involving small (<1Mb) regions were
      detected in most patients and were particularly apparent in the UC progressor
      patients who had dysplasia or cancer. Chromosomal copy gains or losses affecting
      large regions were mainly restricted to dysplastic biopsies. Areas of significant
      chromosomal losses were detected in the UC progressors on chromosomes 2q36, 3q25,
      3p21, 4q34, 4p16.2, 15q22, and 16p13 (p-value?0.04). These results extend our
      understanding of the dynamic nature of pan-colonic genomic instability in this
      disease.

PMID- 22387991
TI  - Lung cancer mortality risk for U.S. menthol cigarette smokers.
AB  - INTRODUCTION: The U.S. Food and Drug Administration is currently assessing the
      public health impact of menthol cigarettes. Results from a recent U.S. cohort
      study, composed largely of Blacks and limited to 12 Southern states, found that
      menthol cigarette smokers had lower risks of lung cancer incidence and mortality
      than nonmenthol smokers. METHODS: We conducted a survival analysis of current
      smokers from the 1987 National Health Interview Survey Cancer Control Supplement
      (n = 4,832), followed for mortality through linkage with the National Death
      Index. We estimated mortality hazard ratios (HRs) for menthol smokers compared
      with nonmenthol smokers, adjusting for a full set of demographic and smoking
      characteristics. RESULTS: The overall HR for lung cancer mortality for menthol
      smokers was 0.69 (95% CI = 0.45-1.06). The HR for lung cancer mortality for
      menthol smokers at ages 50 and over was 0.59 (95% CI = 0.37-0.95). All-cause
      mortality net of lung cancer mortality did not differ for menthol and nonmenthol
      smokers. CONCLUSION: We found evidence of lower lung cancer mortality risk among
      menthol smokers compared with nonmenthol smokers at ages 50 and over in the U.S.
      population. It is not known, however, if these differences are due to the impact
      of menthol on cigarette smoking or long-term differences in cigarette design
      between menthol and nonmenthol cigarettes.

PMID- 22387990
TI  - Where is the pleasure in that? Low hedonic capacity predicts smoking onset and
      escalation.
AB  - INTRODUCTION: Hedonic capacity is a dispositional ability to experience pleasure
      in response to stimuli that are typically rewarding. The ability to derive
      pleasure from natural reinforcers has been relatively overlooked as a risk factor
      for adolescent smoking. The present study sought to provide initial evidence for
      a relationship between hedonic capacity and adolescent smoking onset and
      escalation. METHODS: The sample was composed of 1,106 adolescents participating
      in a prospective longitudinal survey study of adolescent health behaviors.
      Variables were measured via self-report every 6 months for 4 waves of data
      spanning 18 months. We hypothesized that adolescents with lower hedonic capacity
      may be less responsive to natural reinforcers and therefore be prone to take up
      and rely on smoking as a reinforcer. RESULTS: A two-part latent growth curve
      model indicated that adolescents low in hedonic capacity were over two and a half
      times more likely to have smoked a cigarette in the past month at age 15.5 years
      (odds ratio = 2.64, 95% CI = 1.08-6.45) and to show a 90% increase (beta = 0.9, z
      = 2.28, p = .02) in the rate of smoking escalation every 6 months across the
      following 18 months compared with adolescents with high hedonic capacity.
      CONCLUSIONS: This study provides the first evidence implicating hedonic capacity
      as a risk factor for adolescent smoking initiation and progression. Adolescents
      low in hedonic capacity may be an important population to target for smoking
      prevention and smoking cessation efforts possibly through behavioral skills to
      enhance pleasure derived through natural reinforcers.

PMID- 22387992
TI  - Smoking and other correlates of health care services utilization among mandatory
      military recruits in Israel.
AB  - INTRODUCTION: Data on utilization of ambulatory care and the impact of lifestyle
      on health among young adults are scarce. Israeli mandatory military service
      provides a unique opportunity to investigate these topics. Study objective was to
      analyze the utilization of health care services (HCS) during the first year of
      military service, and its associations with health behavior at recruitment, in
      order to plan health services, health classification, and health promotion
      activities. METHODS: We conducted a retrospective cohort study among a
      representative sample of 5,751 mandatory new recruits between January 1, 2004,
      and December 31, 2008. Data were collected from the Israeli Defense Force
      computerized medical and administrative records and from an ongoing health survey
      among military recruits. RESULTS: During their first year of service, recruits
      had, on average, more than 7 visits to the primary care clinic, more than 10
      dispensed nonchronic medications, and more than 5 days of sick leave. Female sex
      (OR = 1.27; 1.06-1.51) and current cigarette smoking (OR = 1.57; 1.34-1.84) were
      significantly associated with increased use of HCS, after controlling for
      possible confounders. CONCLUSIONS: Our findings indicate high utilization of HCS
      during the first year of military service and highlight the potential effect of
      cigarette smoking as a risk factor for increased morbidity among apparently
      healthy young adults. These findings support adding smoking status to fitness
      assessments and could aid health promotion efforts to reduce smoking rates among
      adolescents.

PMID- 22387993
TI  - Socioeconomic implications of tobacco use in Ghana.
AB  - INTRODUCTION: Country-level evidence from Africa on the prevalence of tobacco use
      and the role played by both demographic and socioeconomic factors, as influences
      on the use of tobacco products, is sparse. This paper analyzes the determinants
      of tobacco use in Ghana and explores the association between tobacco use and
      poverty in the country. METHODS: Data from the 2008 Ghana Demographic and Health
      Survey, a nationally representative survey of households (n = 12,323), were used
      to generate descriptive statistics and characterize tobacco use in the country. A
      logistic regression model was used to evaluate the relationships between tobacco
      use and age, place of residence, region, education status, wealth, marital
      status, alcohol use, and whether the person has children. Unadjusted and adjusted
      odds ratios were calculated for tobacco users and nonusers on the likelihood of
      their purchase of selected commodities indicative of living standards. RESULTS:
      Tobacco use was significantly higher among those living in poverty stricken
      regions, those with less education, lower levels of wealth, parents, and alcohol
      users. Tobacco use was significantly higher among men (7%) than women (0.4%), and
      it increased to a peak age of 41.4 years before it declined. Using tobacco was
      also associated with a lower likelihood of purchasing health insurance.
      DISCUSSION: Tobacco use is inextricably related to poverty in Ghana. Policies
      should be formulated to target populations and regions with higher tobacco
      prevalence to combat both poverty and tobacco use simultaneously.

PMID- 22387994
TI  - Reimbursing dentists for smoking cessation treatment: views from dental insurers.
AB  - INTRODUCTION: Screening and delivery of evidence-based interventions by dentists
      is an effective way to reduce tobacco use. However, dental visits remain an
      underutilized opportunity for the treatment of tobacco dependence. This is, in
      part, because the current reimbursement structure does not support expansion of
      dental providers' role in this arena. The purpose of this study was to interview
      dental insurers to assess attitudes toward tobacco use treatment in dental
      practice, pros and cons of offering dental provider reimbursement, and barriers
      to instituting a tobacco use treatment-related payment policy for dental
      providers. METHODS: Semi-structured interviews were conducted with 11 dental
      insurance company executives. Participants were identified using a targeted
      sampling method and represented viewpoints from a significant share of companies
      within the dental insurance industry. RESULTS: All insurers believed that
      screening and intervention for tobacco use was an appropriate part of routine
      care during a dental visit. Several indicated a need for more evidence of
      clinical and cost-effectiveness before reimbursement for these services could be
      actualized. Lack of purchaser demand, questionable returns on investment, and
      segregation of the medical and dental insurance markets were cited as additional
      barriers to coverage. CONCLUSIONS: Dissemination of findings on efficacy and
      additional research on financial returns could help to promote uptake of coverage
      by insurers. Wider issues of integration between dental and medical care and
      payment systems must be addressed in order to expand opportunities for preventive
      services in dental care settings.

PMID- 22387995
TI  - Predictors of quit attempts and abstinence among smokers not currently interested
      in quitting.
AB  - INTRODUCTION: Rates of quitting smoking remain stagnant, and thus it is becoming
      increasingly important to identify determinants of successful quitting behavior.
      The primary purpose of the current study was to examine predictors of quit
      attempts and 7-day point prevalence abstinence in a large nationally based
      sample. The study population consisted exclusively of smokers with minimal
      interest in quitting in the immediate future, for whom the need to identify
      facilitating factors of cessation is highly significant. METHODS: Participants
      consisted of 849 smokers participating in a nationwide population-based
      randomized controlled trial (RCT) to promote quit attempts and cessation; all
      participants were not currently interested in cessation. RESULTS: After adjusting
      for treatment group, and using a multivariate logistic approach, a combination of
      motivational and self-efficacy variables consistently predicted quit attempts,
      regardless of how quit attempts were defined (i.e., any self-defined vs. 24 hr).
      Additionally, a greater number of previous quit attempts significantly predicted
      making future quit attempts. In terms of achieving short-term abstinence,
      regardless of whether analyses were restricted to individuals who made prior quit
      attempts or not, self-efficacy emerged as the only significant consistent
      predictor. CONCLUSIONS: Unlike previous studies, we did not find strong evidence
      suggesting unique predictors for making a quit attempt compared with achieving
      abstinence. Our findings demonstrate that even among smokers not currently
      interested in quitting, self-efficacy and motivation are key factors in the
      cessation process. Overall, the findings have important implications, as they
      highlight factors to target for future treatment.

PMID- 22387996
TI  - Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary
      dyskinesia.
AB  - Primary ciliary dyskinesia most often arises from loss of the dynein motors that
      power ciliary beating. Here we show that DNAAF3 (also known as PF22), a
      previously uncharacterized protein, is essential for the preassembly of dyneins
      into complexes before their transport into cilia. We identified loss-of-function
      mutations in the human DNAAF3 gene in individuals from families with situs
      inversus and defects in the assembly of inner and outer dynein arms. Knockdown of
      dnaaf3 in zebrafish likewise disrupts dynein arm assembly and ciliary motility,
      causing primary ciliary dyskinesia phenotypes that include hydrocephalus and
      laterality malformations. Chlamydomonas reinhardtii PF22 is exclusively
      cytoplasmic, and a PF22-null mutant cannot assemble any outer and some inner
      dynein arms. Altered abundance of dynein subunits in mutant cytoplasm suggests
      that DNAAF3 (PF22) acts at a similar stage as other preassembly proteins, for
      example, DNAAF2 (also known as PF13 or KTU) and DNAAF1 (also known as ODA7 or
      LRRC50), in the dynein preassembly pathway. These results support the existence
      of a conserved, multistep pathway for the cytoplasmic formation of assembly
      competent ciliary dynein complexes.

PMID- 22387997
TI  - A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
AB  - The identification of subtype-specific translocations has revolutionized the
      diagnostics of sarcoma and has provided new insight into oncogenesis. We used RNA
      seq to investigate samples from individuals diagnosed with small round cell
      tumors of bone, possibly Ewing sarcoma, but which lacked the canonical EWSR1-ETS
      translocation. A new fusion was observed between BCOR (encoding the BCL6 co
      repressor) and CCNB3 (encoding the testis-specific cyclin B3) on the X
      chromosome. RNA-seq results were confirmed by RT-PCR and through cloning of the
      tumor-specific genomic translocation breakpoints. In total, 24 BCOR-CCNB3
      positive tumors were identified among a series of 594 sarcoma cases. Gene
      profiling experiments indicated that BCOR-CCNB3-positive cases are biologically
      distinct from other sarcomas, particularly Ewing sarcoma. Finally, we show that
      CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of
      sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S
      phase in NIH3T3 cells. Thus, the intrachromosomal X-chromosome fusion described
      here represents a new subtype of bone sarcoma caused by a newly identified gene
      fusion mechanism.

PMID- 22387998
TI  - A genome-wide association study identifies two susceptibility loci for duodenal
      ulcer in the Japanese population.
AB  - Through a genome-wide association analysis with a total of 7,035 individuals with
      duodenal ulcer and 25,323 controls from Japan, we identified two susceptibility
      loci at the PSCA gene (encoding prostate stem cell antigen) at 8q24 and at the
      ABO blood group locus at 9q34. The C allele of rs2294008 at PSCA was associated
      with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 * 10(
      33)) in a recessive model but was associated with decreased risk of gastric
      cancer (OR = 0.79; P = 6.79 * 10(-12)), as reported previously. The T allele of
      rs2294008 encodes a translation initiation codon upstream of the reported site
      and changes protein localization from the cytoplasm to the cell surface. rs505922
      at ABO was also associated with duodenal ulcer in a recessive model (OR = 1.32; P
      = 1.15 * 10(-10)). Our findings demonstrate a role for genetic variants in the
      pathogenesis of duodenal ulcer.

PMID- 22387999
TI  - Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of
      all-iPS cell mice from terminally differentiated B cells.
AB  - The generation of induced pluripotent stem cells (iPSCs) often results in
      aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster,
      compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC
      mice'). Here, we show that reprogramming in the presence of ascorbic acid
      attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration
      that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This
      approach allowed us to generate all-iPSC mice from mature B cells, which have
      until now failed to support the development of exclusively iPSC-derived postnatal
      animals. Our data show that transcription factor-mediated reprogramming can endow
      a defined, terminally differentiated cell type with a developmental potential
      equivalent to that of embryonic stem cells. More generally, these findings
      indicate that culture conditions during cellular reprogramming can strongly
      influence the epigenetic and biological properties of the resultant iPSCs.

PMID- 22388000
TI  - Complex reorganization and predominant non-homologous repair following
      chromosomal breakage in karyotypically balanced germline rearrangements and
      transgenic integration.
AB  - We defined the genetic landscape of balanced chromosomal rearrangements at
      nucleotide resolution by sequencing 141 breakpoints from cytogenetically
      interpreted translocations and inversions. We confirm that the recently described
      phenomenon of 'chromothripsis' (massive chromosomal shattering and
      reorganization) is not unique to cancer cells but also occurs in the germline,
      where it can resolve to a relatively balanced state with frequent inversions. We
      detected a high incidence of complex rearrangements (19.2%) and substantially
      less reliance on microhomology (31%) than previously observed in benign copy
      number variants (CNVs). We compared these results to experimentally generated DNA
      breakage-repair by sequencing seven transgenic animals, revealing extensive
      rearrangement of the transgene and host genome with similar complexity to human
      germline alterations. Inversion was the most common rearrangement, suggesting
      that a combined mechanism involving template switching and non-homologous repair
      mediates the formation of balanced complex rearrangements that are viable, stably
      replicated and transmitted unaltered to subsequent generations.

PMID- 22388001
TI  - Vascular effects of nebivolol added to hydrochlorothiazide in African Americans
      with hypertension and echocardiographic evidence of diastolic dysfunction: the
      NASAA study.
AB  - BACKGROUND: African Americans have greater risk of cardiovascular events than
      comparator populations of white European origin. A potential reason for this is
      reduced nitric oxide bioavailability in African Americans, resulting in increased
      prevalence of factors that contribute to ventricular dysfunction. We investigated
      the effects of nebivolol with the diuretic hydrochlorothiazide (HCTZ) in
      hypertensive African Americans with echocardiographic evidence of diastolic
      dysfunction. METHODS: A total of 42 African American patients were assigned to
      nebivolol and HCTZ in an open-label fashion for a 24-week period. Changes in
      blood pressure (BP), echocardiographic parameters, and success in attaining
      target BP were determined. As an indirect determinant of endothelial function,
      serum total nitric oxide (NOx) levels and asymmetric dimethyl arginine (ADMA)
      levels were performed at baseline and after the treatment period. RESULTS: The
      systolic BP decreased from 150 +/- 13 to 136 +/- 16 mm Hg (P < .005). Diastolic
      BP decreased from 94 +/- 13 to 84 +/- 9 mm Hg (P = .008). Of the patients that
      completed the study, 77% achieved a combined target BP of systolic BP <140 mm Hg
      and a diastolic BP <90 mm Hg. Serum NOx increased by 41% and 39% in patients that
      were treated with 10 mg and 20 mg daily nebivolol, respectively. The ADMA levels
      decreased by 44% following treatment. The change in systolic BP was strongly
      correlated to the change in ADMA (r = .54; P = .024). Furthermore, in comparison
      to a group of age-matched patients controlled with diuretic therapy only, the
      ADMA levels were significantly lower in the nebivolol posttreatment group
      (controlled BP with diuretic: 0.32 +/- 0.07MUmol/L; nebivolol posttreatment: 0.24
      +/- 0.06 MUmol/L; P < .05). CONCLUSION: Reduced BP with nebivolol in hypertensive
      African Americans and echocardiographic evidence of diastolic dysfunction
      correlates with improved endothelial function. Furthermore, improvement in
      endothelial function and increased nitric oxide bioavailability suggests a
      potential mechanism of efficacy of nebivolol in these patients.

PMID- 22388002
TI  - Dabigatran: comparison to warfarin, pathway to approval, and practical guidelines
      for use.
AB  - Atrial fibrillation (AF) affects more than 3 million Americans and is expected to
      reach epidemic proportions as the US population ages. The presence of AF
      increases lifetime stroke risk nearly 5-fold. Conventionally, patients at
      moderate or high risk of stroke have been prescribed antiplatelet agents or
      vitamin K antagonists to reduce the risk, but each has significant limitations.
      Accordingly, the development of new oral anticoagulants (direct thrombin
      inhibitors [DTIs] and factor Xa inhibitors) has attracted significant interest.
      The DTI dabigatran etexilate was recently shown to provide superior risk
      reduction to warfarin for stroke and systemic embolism for patients with
      nonvalvular AF and recently gained US Food and Drug Administration approval for
      this indication. Dabigatran etexilate is the first new agent for this indication
      in the United States in more than 50 years. Herein, we outline the options for
      stroke prevention in AF in the new oral anticoagulant era. The efficacy and
      practical obstacles surrounding the use of warfarin are summarized. We then
      review the mechanism of action, efficacy, and safety of dabigatran-including
      clinically relevant pharmacokinetics. Practical issues of initiation, conversion
      of anticoagulant therapy, and recommendations for dabigatran use in patients at
      high risk of bleeding and other special populations are discussed. We conclude by
      proposing a role for dabigatran in the armamentarium of drugs available for the
      management of stroke risk in AF.

PMID- 22388003
TI  - Advances in oral drug delivery: improved bioavailability of poorly absorbed drugs
      by tissue and cellular optimization. Preface.

PMID- 22388004
TI  - Delivery of therapeutics to the central nervous system.

PMID- 22388005
TI  - Structural remodeling of the N-terminus tunes TRPA1 channel activation and
      regulates behavioral responses in Drosophila.
AB  - Our bodies are constantly bombarded by a diversity of environmental stimuli, such
      as touch, taste, sound, smell, light, etc. To detect and process this broad array
      of signals, nature has evolved a variety of cellular sensory mechanisms and
      pathways that interface with the environment and transmit neural signals back to
      the CNS where they are translated into behavioral decisions. Transient Response
      Potential (TRP) cation channels were first identified in invertebrates (i.e.,
      Drosophila) and represent a sizeable receptor/channel family in mammals,
      consisting of 28 individual members grouped into subclasses denoted TRPC, TRPV,
      TRPM, TRPML, TRPP and TRPA (for a recent review, see ref. 1). Although originally
      described as ion channels, we now know that many members of the TRP family also
      function as receptors for a range of stimuli, including temperature, pH, chemical
      compounds and membrane voltage. In fact, several TRP isoforms display multimodal
      sensitivity, meaning that they can respond to more than one stimulus. For
      example, TRPV1, or the capcaisin receptor, displays both thermal and chemical
      sensitivity, and the two stimuli may act synergistically to increase channel
      activity. Physiologically, TRP family members are expressed in a variety of
      sensory afferent nerves that feed environmental information to the CNS, and also
      in smaller C-type afferent fibers responsible for peripheral pain sensation and
      transmission. Therapeutically, manipulation of TRP channel activity may represent
      an effective strategy to treat peripheral pain associated with inflammation and
      chronic tissue injury.

PMID- 22388006
TI  - Microtubules cut loose at the cell cortex.
AB  - The ability of the microtubule cytoskeleton to rapidly and locally reorganize
      itself in response to intra- and extracellular signals is essential to its wide
      range of functions. A site of tightly regulated microtubule dynamics--and the
      major interface between the microtubule cytoskeleton and the extracellular
      environment--is the cell cortex, where the selective stabilization and
      destabilization of microtubule plus-ends is required for normal cell division,
      morphogenesis and migration. In a recent study, we found that the cortex of
      Drosophila S2 and D17 cells is coated with the microtubule severing enzyme and
      plus-end depolymerase, Kat-60, which actively suppresses microtubule growth and
      stability along the cell edge. We have proposed that cortical Kat-60 functions by
      uncapping plus-ends, thereby activating another microtubule depolymerase, KLP10A,
      preloaded onto the end. The localized destruction of microtubule plus-ends at a
      specific cortical could feed into larger regulatory pathways, such as those in
      control of the actin cytoskeleton, to influence cell polarization and motility.

PMID- 22388007
TI  - Psychopathology and thought suppression: a quantitative review.
AB  - Recent theories of psychopathology have suggested that thought suppression
      intensifies the persistence of intrusive thoughts, and proposed that difficulty
      with thought suppression may differ between groups with and without
      psychopathology. The current meta-analytic review evaluates empirical evidence
      for difficulty with thought suppression as a function of the presence and
      specific type of psychopathology. Based on theoretical proposals from the
      psychopathology literature, diagnosed and analogue samples were expected to show
      greater recurrence of intrusive thoughts during thought suppression attempts than
      non-clinical samples. However, results showed no overall differences in the
      recurrence of thoughts due to thought suppression between groups with and without
      psychopathology. There was, nevertheless, variation in the recurrence of thoughts
      across different forms of psychopathology, including relatively less recurrence
      during thought suppression for samples with symptoms of Obsessive-Compulsive
      Disorder, compared to non-clinical samples. However, these differences were
      typically small and provided only mixed support for existing theories.
      Implications for cognitive theories of intrusive thoughts are discussed,
      including proposed mechanisms underlying thought suppression.

PMID- 22388008
TI  - Balancing sex chromosome expression and satisfying the sexes.
AB  - Equalizing sex chromosome expression between the sexes when they have largely
      differing gene content appears to be necessary, and across species, is
      accomplished in a variety of ways. Even in birds, where the process is less than
      complete, a mechanism to reduce the difference in gene dose between the sexes
      exists. In early development, while the dosage difference is unregulated and
      still in flux, it is frequently exploited by sex determination mechanisms. The
      Drosophila female sex determination process is one clear example, determining the
      sexes based on X chromosome dose. Recent data show that in Drosophila, the female
      sex not only reads this gene balance difference, but at the same time usurps the
      moment. Taking advantage of the transient default state of male dosage
      compensation, the sex determination master-switch Sex-lethal which resides on the
      X, has its expression levels enhanced before it works to correct the gene
      imbalance. Intriguingly, key developmental genes which could create developmental
      havoc if their levels were unbalanced show more exquisite regulation, suggesting
      nature distinguishes them and ensures their expression is kept in the desirable
      range.

PMID- 22388010
TI  - Understanding infusion administration in the ICU through Distributed Cognition.
AB  - To understand how healthcare technologies are used in practice and evaluate them,
      researchers have argued for adopting the theoretical framework of Distributed
      Cognition (DC). This paper describes the methods and results of a study in which
      a DC methodology, Distributed Cognition for Teamwork (DiCoT), was applied to
      study the use of infusion pumps by nurses in an Intensive Care Unit (ICU). Data
      was gathered through ethnographic observations and interviews. Data analysis
      consisted of constructing the representational models of DiCoT, focusing on
      information flows, physical layouts, social structures and artefacts. The
      findings show that there is significant distribution of cognition in the ICU:
      socially, among nurses; physically, through the material environment; and through
      technological artefacts. The DiCoT methodology facilitated the identification of
      potential improvements that could increase the safety and efficiency of nurses'
      interactions with infusion technology.

PMID- 22388011
TI  - Tree kernel-based protein-protein interaction extraction from biomedical
      literature.
AB  - There is a surge of research interest in protein-protein interaction (PPI)
      extraction from biomedical literature. While most of the state-of-the-art PPI
      extraction systems focus on dependency-based structured information, the rich
      structured information inherent in constituent parse trees has not been
      extensively explored for PPI extraction. In this paper, we propose a novel
      approach to tree kernel-based PPI extraction, where the tree representation
      generated from a constituent syntactic parser is further refined using the
      shortest dependency path between two proteins derived from a dependency parser.
      Specifically, all the constituent tree nodes associated with the nodes on the
      shortest dependency path are kept intact, while other nodes are removed safely to
      make the constituent tree concise and precise for PPI extraction. Compared with
      previously used constituent tree setups, our dependency-motivated constituent
      tree setup achieves the best results across five commonly used PPI corpora.
      Moreover, our tree kernel-based method outperforms other single kernel-based ones
      and performs comparably with some multiple kernel ones on the most commonly
      tested AIMed corpus.

PMID- 22388012
TI  - MysiRNA: improving siRNA efficacy prediction using a machine-learning model
      combining multi-tools and whole stacking energy (DeltaG).
AB  - The investigation of small interfering RNA (siRNA) and its posttranscriptional
      gene-regulation has become an extremely important research topic, both for
      fundamental reasons and for potential longer-term therapeutic benefits. Several
      factors affect the functionality of siRNA including positional preferences,
      target accessibility and other thermodynamic features. State of the art tools aim
      to optimize the selection of target siRNAs by identifying those that may have
      high experimental inhibition. Such tools implement artificial neural network
      models as Biopredsi and ThermoComposition21, and linear regression models as
      DSIR, i-Score and Scales, among others. However, all these models have
      limitations in performance. In this work, a neural-network trained new siRNA
      scoring/efficacy prediction model was developed based on combining two existing
      scoring algorithms (ThermoComposition21 and i-Score), together with the whole
      stacking energy (DeltaG), in a multi-layer artificial neural network. These three
      parameters were chosen after a comparative combinatorial study between five well
      known tools. Our developed model, 'MysiRNA' was trained on 2431 siRNA records and
      tested using three further datasets. MysiRNA was compared with 11 alternative
      existing scoring tools in an evaluation study to assess the predicted and
      experimental siRNA efficiency where it achieved the highest performance both in
      terms of correlation coefficient (R(2)=0.600) and receiver operating
      characteristics analysis (AUC=0.808), improving the prediction accuracy by up to
      18% with respect to sensitivity and specificity of the best available tools.
      MysiRNA is a novel, freely accessible model capable of predicting siRNA
      inhibition efficiency with improved specificity and sensitivity. This
      multiclassifier approach could help improve the performance of prediction in
      several bioinformatics areas. MysiRNA model, part of MysiRNA-Designer package
      [1], is expected to play a key role in siRNA selection and evaluation.

PMID- 22388013
TI  - Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable
      in targeted alpha therapy?
AB  - The interaction between thorium and human serum components was studied using
      difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure
      anion exchange chromatography (HPAEC) with external inductively conducted plasma
      mass spectrometry (ICP-MS) analysis. Experimental data are compared with
      modelling results based on the law of mass action. Human serum transferrin (HSTF)
      interacts strongly with Th(IV), forming a ternary complex including two
      synergistic carbonate anions. This complex governs Th(IV) speciation under blood
      serum conditions. Considering the generally used Langmuir-type model, values of
      10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We
      showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot
      complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not
      related to the competition with HSTF but is due to the strong competition with
      major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be
      stable for a few hours when it is formed before addition in the biological
      medium; this is related to the high kinetic stability of the complex. This makes
      DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules
      for application in targeted alpha therapy.

PMID- 22388015
TI  - Governance of clinical research.
AB  - We review the principal methods and issues in the governance of clinical
      research: oversight of human research by federal offices, certification of
      clinical trial centers, management of conflict of interest in clinical research,
      and trial registration and reporting.

PMID- 22388016
TI  - Management of delayed postpolypectomy bleeding: a decision analysis.
AB  - OBJECTIVES: The benefit of repeat colonoscopy in managing delayed postpolypectomy
      bleeding is unknown. This study aimed to assess the outcome of repeat colonoscopy
      to achieve hemostasis. METHODS: Endoscopic management of postpolypectomy bleeding
      is modeled as a decision tree, measuring the expected overall fraction of
      patients who benefit from therapeutic hemostasis and the number of patients
      needed to treat (NNT) in order to achieve one beneficial hemostasis. RESULTS: A
      repeat colonoscopy to identify and treat postpolypectomy bleeding is beneficial
      in about 22% of patients, corresponding to an NNT of 4.5 patients. The outcome of
      the model is sensitive to assumptions underlying the fractions of patients who
      need treatment and would benefit from successful endoscopic hemostasis. Varying
      these probabilities over a broad range changes the fraction of patients
      benefiting from endoscopy between 3% and 33% and the NNT between 28 and 3
      patients, respectively. CONCLUSIONS: The expected outcome of repeat colonoscopy
      justifies the endoscopic attempts at therapeutic hemostasis. The results also
      suggest that in many patients expectant management aimed at spontaneous
      resolution of the bleeding remains a valid option.

PMID- 22388017
TI  - Images of the month.

PMID- 22388022
TI  - Editorial: single-tablet ibuprofen/double-dose famotidine for reduction of
      gastric and duodenal ulcers (REDUCE Trials): what can be reduced?
AB  - Patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who are at high risk
      of gastroduodenal ulcer complications often do not receive gastroprotective co
      therapy. Fixed-dose combination tablets of an NSAID and a proton-pump inhibitor
      or misoprostol are intended to improve adherence. Whether the use of these
      combination tablets will improve adherence and clinical outcome remains largely
      uninvestigated. Unlike proton-pump inhibitors and misoprostol, the efficacy of
      histamine-2-receptor antagonists in preventing gastroduodenal ulcers associated
      with NSAID use is questionable. Nonetheless, a new fixed-dose combination tablet
      of an NSAID and famotidine will soon be available on the market. The study by
      Laine et al. is a pooled analysis of two large-scale, carefully designed
      randomized trials (REDUCE trials) of a fixed-combination tablet of ibuprofen and
      famotidine on the incidence of endoscopic ulcers. How the study findings may
      influence clinical practice deserves further consideration.

PMID- 22388023
TI  - Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth
      the trouble.
AB  - Non-selective beta-blockers have been a cornerstone of therapy for prevention of
      esophageal variceal bleeding in cirrhosis patients for more than two decades.
      When lowering the hepatic vein portal pressure gradient (HVPG) below 12 mm Hg or
      decreasing the pressure by 20% from baseline, these drugs are of proven benefit
      in reducing variceal bleeding and improving survival in this patient population.
      The recent work by Hendandez-Gea et al., suggests that initiation of the beta
      blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent
      the first occurrence of clinically evident ascites. This finding comes with some
      caveats, however. The beneficial effect was only seen in patients who had an
      improvement by 10% or more from baseline HVPG pressure (only 51% of the treated
      patients in this study). This class of medications has some risk and tolerance
      issues, and many patients do not respond, even when the heart rate is optimally
      decreased. Despite this, the use of beta-blockers may be beneficial in the
      primary prevention of the formation of ascites and further decompensation of
      cirrhosis.

PMID- 22388024
TI  - Editorial: fecal granins in IBS: cause or indicator of intestinal or colonic
      irritation?
AB  - Ohman et al. report increased fecal granins in patients with irritable bowel
      syndrome (IBS). Several interesting questions arise from their observations. Are
      the granins a cause of the pathophysiology or phenotype in IBS? Is the elevation
      of granins specific to IBS? What is the cause of increased fecal granin levels?
      Can fecal granin levels be used to diagnose IBS? Are increased fecal granins an
      expression of intestinal or colonic irritation? This paper adds to the body of
      evidence suggesting there are gastrointestinal disturbances in IBS; understanding
      these disturbances may provide clues to its pathogenesis and optimize management.

PMID- 22388025
TI  - Editorial: sessile serrated adenomas and their pit patterns: we must first see
      the forest through the trees.
AB  - Serrated lesions of the colorectum include hyperplastic polyps, which are non
      neoplastic, and sessile serrated adenomas (SSAs, also known as sessile serrated
      polyps) and traditional serrated adenomas, which are premalignant. It is believed
      that up to 30% of colon cancers and many post-colonoscopy cancers arise from
      serrated neoplasms. Post-colonoscopy cancers have been found to have a molecular
      signature similar to SSAs, including CpG island methylation, BRAF mutations, and
      microsatellite instability. A novel pit pattern, Type II-O, has been demonstrated
      to have a high specificity for SSAs. Unfortunately, the sensitivity is too low to
      utilize a Type II-O pit pattern to determine which serrated lesion is neoplastic
      and needs resection. Moreover, there is significant endoscopist-related
      variability in the detection of serrated lesions of the colon. Efforts to improve
      the detection of serrated neoplasms are warranted.

PMID- 22388026
TI  - Correlation of ePFT and EUS to histology: were these really minimal change
      chronic pancreatitis patients?

PMID- 22388028
TI  - Appropriateness of hepatitis a vaccination in patients with hepatitis C.

PMID- 22388031
TI  - The relative contribution of hepatic encephalopathy to burden in patients with
      cirrhosis.

PMID- 22388032
TI  - 5-aminosalicylates to prevent relapse of Crohn's disease after surgery.

PMID- 22388034
TI  - Chronic rectal bleeding due to Lymphogranuloma venereum proctocolitis.

PMID- 22388035
TI  - Life as a combat gastroenterologist.

PMID- 22388036
TI  - EUS-guided FNA of solid pancreatic masses with or without on-site cytological
      evaluation: more sample adequacy with less needle passes?

PMID- 22388039
TI  - NLRP4 negatively regulates type I interferon signaling by targeting the kinase
      TBK1 for degradation via the ubiquitin ligase DTX4.
AB  - Stringent control of the type I interferon signaling pathway is important for
      maintaining host immune responses and homeostasis, yet the molecular mechanisms
      responsible for its tight regulation are still poorly understood. Here we report
      that the pattern-recognition receptor NLRP4 regulated the activation of type I
      interferon mediated by double-stranded RNA or DNA by targeting the kinase TBK1
      for degradation. NLRP4 recruited the E3 ubiquitin ligase DTX4 to TBK1 for Lys48
      (K48)-linked polyubiquitination at Lys670, which led to degradation of TBK1.
      Knockdown of either DTX4 or NLRP4 abrogated K48-linked ubiquitination and
      degradation of TBK1 and enhanced the phosphorylation of TBK1 and the
      transcription factor IRF3. Our results identify a previously unrecognized role
      for NLRP4 in the regulation of type I interferon signaling and provide molecular
      insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation.

PMID- 22388040
TI  - NF-kappaB-mediated degradation of the coactivator RIP140 regulates inflammatory
      responses and contributes to endotoxin tolerance.
AB  - Tolerance to endotoxins that is triggered by prior exposure to Toll-like receptor
      (TLR) ligands provides a mechanism with which to dampen inflammatory cytokines.
      The receptor-interacting protein RIP140 interacts with the transcription factor
      NF-kappaB to regulate the expression of genes encoding proinflammatory cytokines.
      Here we found lipopolysaccharide stimulation of kinase Syk-mediated tyrosine
      phosphorylation of RIP140 and interaction of the NF-kappaB subunit RelA with
      RIP140. These events resulted in more recruitment of the E3 ligase SCF to
      tyrosine-phosphorylated RIP140, which degraded RIP140 to inactivate genes
      encoding inflammatory cytokines. Macrophages expressing nondegradable RIP140 were
      resistant to the establishment of endotoxin tolerance for specific 'tolerizable'
      genes. Our results identify RelA as an adaptor with which SCF fine tunes NF
      kappaB target genes by targeting the coactivator RIP140 and show an unexpected
      role for RIP140 degradation in resolving inflammation and endotoxin tolerance.

PMID- 22388043
TI  - Exposure therapy leads to enhanced late frontal positivity in 8- to 13-year-old
      spider phobic girls.
AB  - Neurobiological studies have demonstrated that psychotherapy is able to alter
      brain function in adults, however little exists on this topic with respect to
      children. This waiting-list controlled investigation focused on therapy-related
      changes of the P300 and the late positive potential (LPP) in 8- to 13-year-old
      spider phobic girls. Thirty-two patients were presented with phobia-relevant,
      generally disgust-inducing, fear-inducing, and affectively neutral pictures while
      an electroencephalogram was recorded. Participants received one session of up to
      4h of cognitive-behavioral exposure therapy. Treated children showed enhanced
      amplitudes of the LPP at frontal sites in response to spider pictures. This
      result is interpreted to reflect an improvement in controlled attentional
      engagement and is in line with already existing data for adult females. Moreover,
      the girls showed a therapy-specific reduction in overall disgust proneness, as
      well as in experienced arousal and disgust when viewing disgust pictures. Thus,
      exposure therapy seems to have broad effects in children.

PMID- 22388044
TI  - Degree of substitution of chlorin e6 on charged poly-L-lysine chains affects
      their cellular uptake, localization and phototoxicity towards macrophages and
      cancer cells.
AB  - Macromolecular photosensitizer conjugates are under investigation as improved
      delivery vehicles for dyes used in photodynamic therapy. We have previously
      described the use of conjugates between photosensitizers such as chlorine6 (ce6)
      and poly-L-lysine (pL) chains which are versatile molecular species because the
      size of the chain can be varied, and the overall charge can be altered from
      cationic through neutral to anionic. We now report on a series of pL-ce6
      conjugates in their cationic (native), neutral (acetylated) and anionic
      (succinylated) forms, where the number of ce6 molecules attached to each chain
      was varied (pL: ce6 ratios, 1:4, 1:8, 1:12, and 1:16). The fluorescence emissions
      were measured in both saline and a disaggregating solvent. We studied two cell
      lines (an epithelial ovarian cancer, OVCAR-5 and a mouse macrophage, J774) and
      measured cellular uptake, subcellular localization (by confocal fluorescence
      microscopy) and phototoxicity. The cellular uptake of the conjugates with four
      substitution ratios all delivered at 2 MUM ce6 equivalent concentration showed a
      maximum at 12 ce6 per chain for both cationic and anionic conjugates, but the
      uptake of the neutral conjugate was proportional to the substitution ratio. The
      macrophages took up several times more ce6 than the ovarian cancer cells.
      Confocal fluorescence micrographs showed more cellular fluorescence with the
      lower substitution ratios, and more lysosomal localization with the cationic
      conjugates. The phototoxicity was much higher for the neutral conjugates. For the
      cationic and neutral conjugates the 12 ce6 per chain was the most effective at
      killing cells, while for the anionic conjugate it was the 16 ce6 per chain. The
      anionic conjugate was better at killing OVCAR-5 cells, while the cationic was
      better for J774 cells, and the neutral was approximately the same. These data
      will help to optimize the parameters to be used in preparing polymeric
      photosensitizer conjugates for photodynamic therapy.

PMID- 22388045
TI  - Approaching biomimetics in dental restorations via photonics.
AB  - It is established that a natural system balances functional requirements with the
      anatomical optimizations it has achieved. Though such process of functional
      adaptation is recognized in bone tissue, any mode of functional adaptation in
      dental tissue is yet to be understood. In this study a three-dimensional digital
      photoelasticity is conducted to evaluate the nature of stress distribution in the
      sagittal aspect and the cross-sections of the dentine structure. Later, a
      fluoroscopic X-ray microscopic analysis and a microindentation experiments, are
      performed on different sections obtained from the sagittal and cross-sections of
      the dentine. These experiments aided in correlating the multi-plane pattern of
      mineralization and the spatial gradients in elastic modulus in the original
      dentine structure with the three-dimensional stress distribution in photoelastic
      models. This study highlights dentine structure as a biologically graded
      structure to functional loads.

PMID- 22388046
TI  - Enhance light penetration in tissue for high resolution optical imaging
      techniques by the use of biocompatible chemical agents.
AB  - The highly scattering nature of human tissue limits light penetration depth in
      the near infrared range, which prevents the deeper microstructures from imaging.
      In order to enhance the imaging depth for the current high resolution optical
      imaging techniques, the light scattering in tissue must be reduced. This paper
      demonstrates that the light scattering of tissue can be effectively reduced by
      the topical applications of the biocompatible chemical agents. In this study the
      propylene glycol and glucose solutions were chosen for the demonstrations through
      topical applications and intra-dermis injection, respectively. The experiments
      were performed in vitro and in vivo by the use of the optical coherence
      tomography system. The results clearly show that the OCT imaging depth and
      contrast are dramatically improved after the topical applications of propylene
      glycol solution. Such improvement was discussed on the basis of refractive index
      matching environment created by the chemical agents, which effectively reduces
      the light scattering of tissue. Rayleigh-Gans approximation of light scattering
      was also used to show theoretically how the increase of refractive index of
      background medium would have effect on the reduced scattering coefficient of
      tissue. The theoretical and experimental results were qualitatively consistent.

PMID- 22388047
TI  - Interstitial laser thermotherapy of a rat liver adenocarcinoma.
AB  - The aim of this study was to compare interstitial laser thermotherapy with
      excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was
      implanted into the left lateral lobe of the rat liver, and treatment was
      performed 8 days later. Rats were treated with resection of the tumour-bearing
      lobe or underwent interstitial laser thermotherapy, which was performed at a
      steady-state temperature of 46 degrees C for 30 min, 3 mm from the tumour margin.
      The incidence and extent of intraperitoneal spread was smaller after laser
      thermotherapy than after resection, with no difference in local control. Using
      inoculation of tumour cell suspensions into the lateral and the median lobes of
      the liver simultaneously and treating the lateral lobe tumour only, we found that
      laser thermotherapy reduced take and growth of the untreated tumour in the median
      lobe indicating that laser thermotherapy may induce immunologic effects. It is
      concluded that interstitial laser thermotherapy reduces spread of liver tumour as
      compared to resection. It is suggested that this can be at least partly explained
      by a laser-induced immunologic effect.

PMID- 22388048
TI  - Fundamental study on non-invasive blood glucose sensing.
AB  - Diabetes is a disease which severely threatens the health of human beings.
      Unfortunately, current monitoring techniques with finger sticks discourage the
      regular use. Noninvasive spectroscopic measurement of blood glucose is a simple
      and painless technique, and reduces the long-term health care costs of diabetic
      patients due to no reagents. It is suitable for home use. Moreover, the
      establishment of the methodology not only applies to blood glucose noninvasive
      measurement, but also can be extended to noninvasive measurement of other
      analytes in body fluid, which will be of important significance for the
      development of the technique of clinical analysis. In this paper, some
      fundamental researches, which have been achieved in our laboratory in the field
      of non-invasive blood glucose measurement, were introduced.  1. Fundamental
      research was done for the glucose concentrations from simple to complex samples
      with near and middle infrared spectroscopy:  (1) the relationship between the
      instrument precision and prediction accuracy of the glucose measurement; (2) the
      change of the result of the quantitative measurement with the change of the
      complexity of samples; (3) the attempt of increasing the prediction accuracy of
      the glucose measurement by improving the methods of modeling. The research
      results showed that it is feasible for non-invasive blood glucose measurement
      with near and middle infrared spectroscopy in theory, and the experimental
      results, from simple to complex samples, proved that it is effective for the
      methodology consisting of hardware and software.  2. According to the
      characteristics of human body measurement, the effects of measuring conditions on
      measurement results, such as: (1) the effect of measurement position; (2) the
      effect of measurement pressure; (3) the effect of measurement site; (4) the
      effect of measured individual, were investigated. With the fundamental
      researches, the special problems of human body measurement were solved. In
      addition, the practical and effective method of noninvasive human blood glucose
      measurement was proposed.

PMID- 22388049
TI  - X-ray microscopy using alkali-halide crystals.
AB  - The materials on the basis of alkali-halide crystals for recording the X-ray
      images are developed. Their spatial resolution is 1 MUm, dynamic range of
      recording is more than 10000. The media allow readout without erasing the image
      and extended storage of the image. The examples of their use in X-ray microscopy
      of biological objects are shown.

PMID- 22388050
TI  - Experimental evaluation on the transmission optical microscopy for the diagnosis
      of lymphedema.
AB  - The mechanisms of disturbance of lymph microcirculation during development
      postmastectomy lymphedema (PML) are little known. The study of these mechanisms
      on human subjects has many difficulties: time of clinical onset of PML is
      indefinite and unpredictable and the methods for imaging of microlymphatics are
      limited. The advantages of the optical methods, especially, light microscopy are
      the high quality of lymphocytes dynamic imaging, possibility of the determination
      of absolute lymph flow velocity in a wide range, capability for simultaneous
      registration of blood microvessel function around lymphatics. The experimental
      lymphedema is created on rat mesentery by ligation of the collecting vein. It was
      found that after such ligation edema was clearly developed, and microcirculation
      was significantly disturbed including reduction of lymph flow velocity,
      constriction of lymphatics, inhibition of phasic activity on the background of
      pathological increasing of blood vessels permeability and stasis of blood flow.

PMID- 22388051
TI  - Synergistic effect of photothermal and photoimmunological reactions in treatment
      of metastatic tumors.
AB  - The use of several different drugs and different treatment modalities often leads
      to synergistic effects in treating diseases, such as cocktail therapy in AIDS
      treatment and combination therapy in chemotherapy treatment of cancer patients.
      With the wide application of lasers in the treatment of cancers, can the
      synergistic effect manifest itself in the combination application of lasers and
      other treatment components, particularly those related to immunological
      stimulation? Selective photothermal interactions using a laser and a light
      absorbing dye have been used in combination with immunological interactions using
      an in situ immunoadjuvant in treating metastatic tumors. Three components were
      used in this method: a near-infrared laser, a ligh-tabsorbing dye and an
      immunoadjuvant. This new method - Laser Immunotherapy - has achieved the
      synergistic effect. This novel approach has been applied in treating metastatic
      mammary tumors in rats. In our animal studies, when the components were applied
      individually, or in two-component combinations, the long-term effect of cancer
      treatment was almost negligible. However, when the three components were used at
      the same time, the treatment effect improved significantly. In this study, we
      show the synergistic effect using an 805 nm laser, indocyanine green (ICG) as the
      light-absorbing dye, and glycated chitosan, a novel compound, as the
      immunostimulant. Furthermore, optimization of the laser-dye photothermal
      interaction using different laser and dye parameters in an in vitro study using
      tissue-simulating gel phantoms was performed. Our results showed that the optimal
      photothermal effect could be achieved using 1.8 watts and 0.5 cm beam radius, and
      an ICG concentration between 0.08 to 0.14% in the target gel. To study the effect
      of immunoadjuvant, three additional adjuvants, complete Freund's adjuvant,
      incomplete Freund's adjuvant, and C-parvum were also used in laser immunotherapy.
      Glycated chitosan appeared to be the most effective. The complete Freund's
      adjuvant at a dose of 200 MUl and 50% concentration resulted in a cure rate
      comparable to that using glycated chitosan. Incomplete Freund's adjuvant and C
      parvum showed relative weak effects in treating the metastatic tumors.

PMID- 22388052
TI  - Selective laser-induced hyperthermia for the treatment of spontaneous tumors in
      dogs.
AB  - Indocyanine green (ICG), with spectral absorption at 800-810 nm, is a chromophore
      that strongly absorbs and converts near-infrared laser energy into thermal
      energy. By directly injecting ICG into a tumor, selective tumor hyperthermia
      during laser irradiation occurs. In this study, 4 dogs with spontaneous tumors
      were injected in situ with a 0.25% wt/vol ICG solution and immediately irradiated
      with 810 nm laser energy. Thermal data were collected from multiple thermocouples
      placed within the tumor and tumor response was recorded. Tissue heating to >= 42
      degrees C was observed in all tumors. One dog had a complete remission, one dog
      had stable disease for 12 weeks, and the other 2 dogs developed progressive
      disease shortly after treatment. Results from this study demonstrate that
      chromophore-enhanced laser-induced hyperthermia can effectively and selectively
      heat canine tumors. However, tumor size and pigmentation of overlying skin are
      potentially limiting factors to the success of this novel c ancer treatment.

PMID- 22388054
TI  - Cyclodextrin-based nanogels for pharmaceutical and biomedical applications.
AB  - Hydrophilic nanogels combine the advantages of hydrogels with certain advantages
      that are inherent in their nanoscale size. Similar to macrogels, nanogels can
      contain and protect drugs and regulate their release by incorporating high
      affinity functional groups, stimuli-responsive conformations and biodegradable
      bonds into the polymer network. Similar to nanoparticles, nanogels can easily be
      administered in liquid form for parenteral drug delivery. The nanoscale size of
      nanogels gives them a high specific surface area that is available for further
      bioconjugation of active targeting agents. Biodistribution and drug release can
      be modulated through size adjustments. The incorporation of hydrophilic
      cyclodextrin (CD) moieties into the polymeric network of the nanogels provides
      them with a drug loading and release mechanism that is based on the formation of
      inclusion complexes without decreasing the hydrophilicity of the network. The
      covalent attachment of CD molecules to the chemically crosslinked networks may
      enable the CDs to display fully their ability to form complexes, while
      simultaneously preventing drug release upon media dilution. The preparation,
      characterization and advantages for pharmaceutical and biomedical applications of
      CD-based nanogels are reviewed in this article.

PMID- 22388053
TI  - Impaired beta-adrenoceptor-induced relaxation in small mesenteric arteries from
      DOCA-salt hypertensive rats is due to reduced K(Ca) channel activity.
AB  - beta-Adrenoceptor (beta-AR)-mediated relaxation plays an important role in the
      regulation of vascular tone. beta-AR-mediated vascular relaxation is reduced in
      various disease states and aging. We hypothesized that beta-AR-mediated
      vasodilatation is impaired in DOCA-salt hypertension due to alterations in the
      cAMP pathway. beta-AR-mediated relaxation was determined in small mesenteric
      arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To
      exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses
      were determined in the presence of l-NNA and indomethacin, NO synthase inhibitor
      and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was
      reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA)
      inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not
      abolish the difference in ISO-induced relaxation between the groups. Forskolin
      (adenylyl cyclase activator)-induced relaxation was similar between the groups.
      The inhibition of IK(Ca)/SK(Ca) channels (TRAM-34 plus UCL1684) or BK(Ca)
      channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and
      abolished the relaxation differences between the groups. The expression of SK(Ca)
      channel was decreased in DOCA-salt arteries. The expression of BK(Ca) channel
      alpha subunit was increased whereas the expression of BK(Ca) channel beta subunit
      was decreased in DOCA-salt arteries. The expression of receptor for activated C
      kinase 1 (RACK1), which is a binding protein for BK(Ca) channel and negatively
      modulates its activity, was increased in DOCA-salt arteries. These results
      suggest that the impairment of beta-AR-mediated relaxation in DOCA-salt
      mesenteric arteries may be attributable to altered IK(Ca)/SK(Ca) and/or BK(Ca)
      channels activities rather than cAMP/PKA pathway. Impaired beta-AR-stimulated
      BK(Ca) channel activity may be due to the imbalance between its subunit
      expressions and RACK1 upregulation.

PMID- 22388055
TI  - Presentation and conservative management of acute calcific tendinopathy: a case
      study and literature review.
AB  - BACKGROUND: The efficacy of a variety of noninvasive, conservative management
      techniques for calcific tendinopathy has been investigated and established for
      improving pain and function and/or facilitating a decrease in the size or
      presence of calcium deposits. Surprisingly, few have reported on the use of
      traditional therapeutic exercise and rehabilitation alone in the management of
      this condition, given the often spontaneous resorptive nature of calcium
      deposits. The purpose of this case is to present the results of a conservative
      approach, including therapeutic exercise, for the management of calcific
      tendinopathy of the supraspinatus, with an emphasis on patient outcomes. CASE
      DESCRIPTION: The patient was a self-referred 41-y-old man with complaints of
      acute right-shoulder pain and difficulty sleeping. Imaging studies revealed
      liquefied calcium deposits in the right supraspinatus. The patient reported
      constant pain at rest (9/10) and tenderness in the area of the greater
      tuberosity. He exhibited a decrease in all shoulder motions and had reduced
      strength. The simple shoulder test (SST) revealed limited function (0/12).
      Conservative management included superficial modalities and medication for pain
      and a regimen of scapulothoracic and glenohumeral range-of-motion (ROM) and
      strengthening exercises. OUTCOMES: At discharge, pain levels decreased to 0/10
      and SST scores increased to 12/12. ROM was full in all planes, and resisted
      motion was strong and pain free. The patient was able to engage in endurance
      activities and continue practicing as a health care provider. DISCUSSION: The
      outcomes with respect to pain, function, and patient satisfaction provide
      evidence to support the use of conservative therapeutic interventions when
      managing patients with acute cases of calcific tendinopathy. Successful
      management of calcific tendinopathy requires attention to outcomes and an
      understanding of the pathophysiology, prognostic factors, and physical
      interventions based on the current stage of the calcium deposits and the
      patient's status in the healing continuum.

PMID- 22388056
TI  - Re: Preparing nurses for the 21st century: perceptions of nurse managers, nursing
      faculty, and staff nurse.

PMID- 22388057
TI  - Does uranium induce circulatory diseases? First results from a French cohort of
      uranium workers.
AB  - OBJECTIVES: Increased risk of circulatory system diseases (CSDs) was observed in
      nuclear workers handling uranium and plutonium in Russia and the UK. This work
      examines the CSD mortality after chronic intake of uranium among 2897 workers
      (79,892 person-years) at a uranium processing plant (1960-2006) in France.
      METHODS: Cumulative exposure to different uranium compounds, classified by their
      isotopic composition and solubility type, was quantified on the basis of a plant
      specific job-exposure matrix and individual job histories. HRs and associated 95%
      CI for CSD (n = 111) and specific CSD categories were estimated using Cox
      regression models, stratified on sex and birth cohort and adjusted for potential
      confounders. The effect of smoking was analysed among 260 smokers (42 CSD
      deaths). RESULTS: Compared to unexposed workers, CSD mortality was increased
      among workers exposed to slowly soluble reprocessed uranium (RPU) (HR = 2.13, 95%
      CI = 0.96 to 4.70) and natural uranium (HR = 1.73, 95% CI = 1.11 to 2.69). The
      risk increased with cumulative exposure and exposure duration. In the subgroup of
      smokers, the risk estimates were higher but with larger CIs: HR=1.91 (95% CI =
      0.92 to 3.98) for natural uranium and HR = 4.78 (95% CI = 1.38 to 16.50) for RPU.
      CONCLUSIONS: The authors observed that exposure to slowly soluble uranium, namely
      RPU, may increase the risk of CSD mortality. However, these results are
      preliminary since the study is lacking statistical power and many other
      biological and lifestyle-related factors may cause CSD. More detailed
      investigations are necessary to confirm these findings and analyse in depth the
      effects of internal radiation exposure on the circulatory system.

PMID- 22388069
TI  - Bone cement embolism.

PMID- 22388070
TI  - A threnody for pain.

PMID- 22388071
TI  - A funny thing happened on the way to the ICU.

PMID- 22388072
TI  - Covalent protein binding and tissue distribution of houttuynin in rats after
      intravenous administration of sodium houttuyfonate.
AB  - AIM: To investigate the potential of houttuynin to covalently bind to proteins in
      vitro and in vivo and to identify the adduct structures. METHODS: Male Sprague
      Dawley rats were intravenously injected with sodium houttuyfonate (10 mg/kg). The
      concentrations of houttuynin in blood, plasma and five tissues tested were
      determined using an LC/MS/MS method. The covalent binding values of houttuynin
      with hemoglobin, plasma and tissue proteins were measured in rats after
      intravenous injection of [1-(14)C]sodium houttuyfonate (10 mg/kg, 150 mCi/kg).
      Human serum albumin was used as model protein to identify the modification
      site(s) and structure(s) through enzymatic digestion and LC/MS(n) analysis.
      RESULTS: The drug was widely distributed 10 min after intravenous injection. The
      lungs were the preferred site for disposition, followed by the heart and kidneys
      with significantly higher concentrations than that in the plasma. The extent of
      covalent binding was correlated with the respective concentrations in the
      tissues, ranging from 1137 nmol/g protein in lung to 266 nmol/g protein in liver.
      Houttuynin reacted primarily with arginine residues in human serum albumin to
      form a pyrimidine adduct at 1:1 molar ratio. The same adduct was detected in rat
      lungs digested by pronase E. CONCLUSION: This study showed that the beta-keto
      aldehyde moiety in houttuynin is strongly electrophilic and readily confers
      covalent binding to tissue proteins, especially lung proteins, by a Schiff's base
      mechanism. The findings explain partially the idiosyncratic reactions of
      houttuyniae injection in clinical use.

PMID- 22388073
TI  - Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1
      murine breast cancer model.
AB  - AIM: To investigate the effects of piperine, a major pungent alkaloid present in
      Piper nigrum and Piper longum, on the tumor growth and metastasis of mouse 4T1
      mammary carcinoma in vitro and in vivo, and elucidate the underlying mechanisms.
      METHODS: Growth of 4T1 cells was assessed using MTT assay. Apoptosis and cell
      cycle of 4T1 cells were evaluated with flow cytometry, and the related proteins
      were examined using Western blotting. Real-time quantitative PCR was applied to
      detect the expression of matrix metalloproteinases (MMPs). A highly malignant,
      spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to
      evaluate the in vivo antitumor activity. Piperine was injected into tumors every
      3 d for 3 times. RESULTS: Piperine (35-280 MUmol/L) inhibited the growth of 4T1
      cells in time- and dose-dependent manners (the IC(50) values were 105 +/- 1.08
      and 78.52 +/- 1.06 MUmol/L, respectively, at 48 and 72 h). Treatment of 4T1 cells
      with piperine (70-280 MUmol/L) dose-dependently induced apoptosis of 4T1 cells,
      accompanying activation of caspase 3. The cells treated with piperine (140 and
      280 MUmol/L) significantly increased the percentage of cells in G(2)/M phase with
      a reduction in the expression of cyclin B1. Piperine (140 and 280 MUmol/L)
      significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1
      cell migration in vitro. Injection of piperine (2.5 and 5 mg/kg) dose-dependently
      suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg)
      significantly inhibited the lung metastasis. CONCLUSION: These results
      demonstrated that piperine is an effective antitumor compound in vitro and in
      vivo, and has the potential to be developed as a new anticancer drug.

PMID- 22388074
TI  - Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in
      gerbils.
AB  - AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal
      auditory nerve function with preservation of normal cochlear hair cells. This
      study was designed to investigate whether treatment with molecular hydrogen
      (H(2)), which can remedy damage in various organs via reducing oxidative stress,
      inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils.
      METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to
      the round window membrane in male Mongolian gerbils. H(2) treatment was given
      twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h
      after ouabain application. Before and 7 d after ouabain application, the hearing
      status of the animals was evaluated using the auditory brainstem response (ABR)
      approach, the hear cell function was evaluated with distortion product
      otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes
      in the cochleae, especially the spiral ganglion neurons (SGNs), were
      morphologically studied. TUNEL staining and immunofluorescent staining for
      activated caspase-3 were used to assess the apoptosis of SGNs. RESULTS: Treatment
      with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR
      threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local
      ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8,
      and 16 kHz. Morphological study showed that treatment with H(2) (2%)
      significantly alleviated SGN damage and attenuated the loss of SGN density for
      each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused
      significantly higher numbers of apoptotic SGNs in the cochlea, which was
      significantly attenuated by the H(2) treatment. However, ouabain did not change
      the morphology of cochlear hair cells. CONCLUSION: The results demonstrate that
      H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus,
      H(2) might be a potential agent for treating hearing impairment in AN patients.

PMID- 22388075
TI  - Imatinib induces H2AX phosphorylation and apoptosis in chronic myelogenous
      leukemia cells in vitro via caspase-3/Mst1 pathway.
AB  - AIM: Histone H2AX is a novel tumor suppressor and its phosphorylation at the C
      terminus (Ser139 and Tyr142) is required for tumor cell apoptosis. The aim of the
      present study was to elucidate the mechanisms underlying imatinib-induced C
      terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.
      METHODS: BCR-ABL-positive K562 cells were used. Microscopy, Western blotting and
      flow cytometry were used to study the signaling pathways that regulate imatinib
      induced H2AX phosphorylation and the apoptotic mechanisms. RESULTS: Treatment of
      K562 cells with imatinib (1-8 MUmol/L) induced phosphorylation of H2AX at Ser139
      and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same
      concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX
      maintained a higher level in the cells. Meanwhile, imatinib (1-8 MUmol/L)
      activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1), and
      induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD (40 MUmol/L)
      reduced imatinib-induced H2AX phosphorylation at Ser139 and Tyr142 and blocked
      imatinib-induced apoptosis of K562 cells. Imatinib (4 MUmol/L) induced expression
      of Williams-Beuren syndrome transcription factor (WSTF), but not wild-type p53
      induced phosphatase 1 (Wip1) in K562 cells. CONCLUSION: The caspase-3/Mst1
      pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and
      subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.

PMID- 22388077
TI  - Motivations of patients with pulmonary arterial hypertension to participate in
      randomized clinical trials.
AB  - BACKGROUND: There is substantial need to rigorously evaluate existing and new
      therapies for pulmonary arterial hypertension (PAH) and other severe and
      relatively rare conditions affecting younger patients. However, the ability to
      conduct meaningful randomized clinical trials (RCTs) in such contexts often is
      limited by difficulties obtaining adequate patient enrollment. PURPOSE: To
      understand the motivations of patients with PAH for participating in RCTs so as
      to facilitate enrollment in future trials among patients with similar diseases.
      METHODS: We conducted semistructured interviews of a diverse sample of patients
      with World Health Organization (WHO) Group I PAH. We purposefully recruited a
      diverse sample of participants until theoretical saturation was reached. We
      randomly assigned patients to review hypothetical RCTs that did or did not allow
      continuation of background PAH therapies and elicited their reasons for or
      against enrolling. Interviews were transcribed and analyzed using constant
      comparison techniques to code and sort data into discrete themes. RESULTS: The 26
      PAH patients enrolled before theoretical saturation was reached identified 24
      factors that would influence their RCT enrollment decisions. These factors
      grouped naturally into four themes: (1) personal medical benefits, (2) personal
      medical risks/harms, (3) nonmedical benefits, and (4) nonmedical burdens.
      Personal benefits were cited as commonly as altruistic motives. One third of the
      patients (9/26) suggested that they would defer enrollment decisions to their
      treating clinicians. Seventy-nine percent of patients (11/14) assigned to
      consider trials without background therapies expressed concerns about clinical
      deterioration (vs. 17% (2/12) among patients assigned to consider trials allowing
      background therapies). LIMITATIONS: The sample was recruited from a single
      academic center. Furthermore, the use of hypothetical trials may not elicit
      identical decision-making processes as may be used among patients contemplating
      actual trial participation. CONCLUSION: For PAH patients considering RCT
      enrollment, the potentials for personal benefit and risk are at least as
      important as altruistic motives. Minimizing the time demands of participating,
      financial remuneration, and allowing participants to continue current therapies
      are factors, which might enhance enrollment to trials in similar disease areas.

PMID- 22388088
TI  - Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor
      initiating cells via activation of key transcription factors and a positive
      feedback signaling loop.
AB  - New cancer therapies are likely to arise from an in-depth understanding of the
      signaling networks influencing tumor initiation, progression and metastasis. We
      show a fundamental role for Src-homology 2 domain-containing phosphatase 2 (SHP2)
      in these processes in human epidermal growth factor receptor 2 (HER2)-positive
      and triple-negative breast cancers. Knockdown of SHP2 eradicated breast tumor
      initiating cells in xenograft models, and SHP2 depletion also prevented invasion
      in three-dimensional cultures and in a transductal invasion assay in vivo.
      Notably, SHP2 knockdown in established breast tumors blocked their growth and
      reduced metastasis. Mechanistically, SHP2 activated stemness-associated
      transcription factors, including v-myc myelocytomatosis viral oncogene homolog (c
      Myc) and zinc finger E-box binding homeobox 1 (ZEB1), which resulted in the
      repression of let-7 microRNA and the expression of a set of 'SHP2 signature'
      genes. We found these genes to be simultaneously activated in a large subset of
      human primary breast tumors that are associated with invasive behavior and poor
      prognosis. These results provide new insights into the signaling cascades
      influencing tumor-initiating cells as well as a rationale for targeting SHP2 in
      breast cancer.

PMID- 22388089
TI  - Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell
      fate in chronic liver disease.
AB  - During chronic injury a population of bipotent hepatic progenitor cells (HPCs)
      become     activated to regenerate both cholangiocytes and hepatocytes. Here we
      show in human diseased     liver and mouse models of the ductular reaction that
      Notch and Wnt signaling direct     specification of HPCs via their interactions
      with activated myofibroblasts or macrophages. In     particular, we found that
      during biliary regeneration, expression of Jagged 1 (a Notch ligand)     by
      myofibroblasts promoted Notch signaling in HPCs and thus their biliary
      specification to     cholangiocytes. Alternatively, during hepatocyte
      regeneration, macrophage engulfment of     hepatocyte debris induced Wnt3a
      expression. This resulted in canonical Wnt signaling in nearby HPCs, thus
      maintaining expression of Numb (a cell fate determinant) within these cells and
      the promotion of their specification to hepatocytes. By these two pathways adult
      parenchymal regeneration during chronic liver injury is promoted.

PMID- 22388090
TI  - Vitamin E decreases bone mass by stimulating osteoclast fusion.
AB  - Bone homeostasis is maintained by the balance between osteoblastic bone formation
      and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are
      formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin
      D are pivotal in maintaining skeletal integrity. However, the role of vitamin E
      in bone remodeling is unknown. Here, we show that mice deficient in alpha
      tocopherol transfer protein (Ttpa(-/-) mice), a mouse model of genetic vitamin E
      deficiency, have high bone mass as a result of a decrease in bone resorption.
      Cell-based assays indicated that alpha-tocopherol stimulated osteoclast fusion,
      independent of its antioxidant capacity, by inducing the expression of dendritic
      cell-specific transmembrane protein, an essential molecule for osteoclast fusion,
      through activation of mitogen-activated protein kinase 14 (p38) and
      microphthalmia-associated transcription factor, as well as its direct recruitment
      to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormality
      seen in Ttpa(-/-) mice was rescued by a Tm7sf4 transgene. Moreover, wild-type
      mice or rats fed an alpha-tocopherol-supplemented diet, which contains a
      comparable amount of alpha-tocopherol to supplements consumed by many people,
      lost bone mass. These results show that serum vitamin E is a determinant of bone
      mass through its regulation of osteoclast fusion.

PMID- 22388092
TI  - Outcome after out-of-hospital cardiac arrest witnessed by EMS: changes over time
      and factors of importance for outcome in Sweden.
AB  - BACKGROUND: Among patients who survive after out-of-hospital cardiac arrest
      (OHCA), a large proportion are recruited from cases witnessed by the Emergency
      Medical Service (EMS), since the conditions for success are most optimal in this
      subset. AIM: To evaluate outcome after EMS-witnessed OHCA in a 20-year
      perspective in Sweden, with the emphasis on changes over time and factors of
      importance. METHODS: All patients included in the Swedish Cardiac Arrest Register
      from 1990 to 2009 were included. RESULTS: There were 48,349 patients and 13.5% of
      them were EMS witnessed. There was a successive increase in EMS-witnessed OHCA
      from 8.5% in 1992 to 16.9% in 2009 (p for trend<0.0001). Among EMS-witnessed
      OHCA, the survival to one month increased from 13.9% in 1992 to 21.8% in 2009 (p
      for trend<0.0001). Among EMS-witnessed OHCA, 51% were found in ventricular
      fibrillation, which was higher than in bystander-witnessed OHCA, despite a lower
      proportion with a presumed cardiac aetiology in the EMS-witnessed group. Among
      EMS-witnessed OHCA overall, 16.0% survived to one month, which was significantly
      higher than among bystander-witnessed OHCA. Independent predictors of a
      favourable outcome were: (1) initial rhythm ventricular fibrillation; (2) cardiac
      aetiology; (3) OHCA outside home and (4) decreasing age. CONCLUSION: In Sweden,
      in a 20-year perspective, there was a successive increase in the proportion of
      EMS-witnessed OHCA. Among these patients, survival to one month increased over
      time. EMS-witnessed OHCA had a higher survival than bystander-witnessed OHCA.
      Independent predictors of an increased chance of survival were initial rhythm,
      aetiology, place and age.

PMID- 22388093
TI  - A study on the section sensitivity profile in multi-row-detector spiral CT.
AB  - The section sensitivity profile (SSP) was well understood in the case of single
      row-detector spiral CT. With the introduction of multi-row-detector spiral CT and
      the transition into cone-beam spiral CT, a revisit to the SSP issue becomes
      necessary. In this paper, the SSP of multi-row-detector spiral CT is formulated
      for the half-scan interpolation method at any transverse position. Based on the
      SSP formula, numerical simulation is performed to quantify the characteristics of
      the SSP with the number of detector rows up to 40. It is shown that the SSP
      varies as a function of the pitch and the number of detector rows. Given an
      appropriate selection of the pitch and the number of detector rows, the SSP does
      not change very much over the field of view in terms of the mean, the slice
      thickness, and the skewness of the SSP. Although in general applications the SSP
      at the gantry iso-center can be used as the representative of the SSP family, for
      more accurate analyses the spatial variation of the SSP must be taken into
      account.

PMID- 22388094
TI  - Development of blind image deconvolution and its applications.
AB  - This paper is a supplement and update to the reviews by Kundur and Hatzinakos
      [7,8] on blind image deconvolution. Most of the methods reviewed in [7,8] require
      that the PSF and the original image must be irreducible. However, this
      irreducibility assumption is not true in some important types of applications,
      such as when the PSF is Gaussian, which is a good model for many imaging systems.
      After a brief summary of existing blind deconvolution methods, we report the
      recent development in this field with an emphasis on Gaussian blind deconvolution
      and its clinical applications.

PMID- 22388091
TI  - IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice
      and enhances mouse and human airway smooth muscle contraction.
AB  - Emerging evidence suggests that the T helper 17 (T(H)17) subset of alphabeta T
      cells contributes to the development of allergic asthma. In this study, we found
      that mice lacking the alphavbeta8 integrin on dendritic cells did not generate
      T(H)17 cells in the lung and were protected from airway hyper-responsiveness in
      response to house dust mite and ovalbumin sensitization and challenge. Because
      loss of T(H)17 cells inhibited airway narrowing without any obvious effects on
      airway inflammation or epithelial morphology, we examined the direct effects of
      T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin
      17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of
      airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear
      factor kappa light-chain enhancer of activated B cells (NF-kappaB)-ras homolog
      gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase
      2 (ROCK2) signaling cascade. Mice lacking integrin alphavbeta8 on dendritic cells
      showed impaired activation of this pathway after ovalbumin sensitization and
      challenge, and the diminished contraction of the tracheal rings in these mice was
      reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells
      contributes to allergen-induced airway hyper-responsiveness through direct
      effects on airway smooth muscle.

PMID- 22388095
TI  - Commissioning of mini-multi-leaf-collimator (MMLC) for stereotactic radiosurgery
      and radiotherapy.
AB  - Commissioning of a Radionics miniature multi-leaf collimator (MMLC) for
      stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) is reported.
      With single isocenter and multi static fields, the MMLC can provide better
      conformity of dose distributions to the target and/or irregularly shaped target
      volumes than standard arc (circular) field beams with multiple isocenters.
      Advantages offered by the MMLC over traditional LINAC based SRS and SRT includes
      greatly improved dose homogeneity to the target, reduced patient positioning time
      and reduced treatment time. In this work, the MMLC is attached to a Varian 2300
      C/D with Varian 80-leaf multi-leaf collimator. The MMLC has 62 leaves, each
      measured to a width of 3.53 mm at isocenter, with fields range from 1x1 cm to
      less than 10 * 12 cm. Beam parameters required by the Radionics treatment
      planning system (XPlan version 2) for evaluating the dose include tissue maximum
      ratio (TMR), scatter factors (SF), off-axis ratios (OAR), output factors,
      penumbra function (P) and transmission factors (TF) are performed in this work.
      Beam data are acquired with a small stereotactic diode, standard ion chambers and
      radiographic films. Measured profiles of dose distribution are compared to those
      calculated by the software and absolute dosimetry is performed.

PMID- 22388096
TI  - A general theoretical formalism for X-ray phase contrast imaging.
AB  - The in-line phase-contrast imaging has great potential for clinical imaging
      applications. This work presents a general theoretical formalism for the in-line
      phase-contrast imaging. The theoretical formalism developed in this work is
      derived by taking a new strategy to calculate the Fourier transform of image
      intensity directly. Different from the transport of intensity equation (TIE)
      formalism for phase-contrast imaging in literature [6], this general formalism
      covers both the near field regime and the holography regime of phase-contrast
      imaging. The image intensity formulas have been derived in both the image space
      and frequency space. Especially our results show that the Fresnel diffraction
      image intensity is a sum of convolutions of the cosine- and sine-Fresnel filters
      with the object attenuation A20(x) and attenuated phase A20(x)phi(x),
      respectively. The Pogany-Gao-Wilkins (PGW) formalism is recovered as a special
      case of our general formalism. In addition, in the low-resolution approximation,
      the general formula is reduced a spherical wave-generalization of the TIE-based
      formula for phase-contrast imaging. This spherical wave-generalization will be
      useful for phase-contrast imaging with a micro-focus x-ray tube. The transition
      of the formalism from 1-D to 2-D cases has been provided as well.

PMID- 22388097
TI  - Mesenchymal stem cells enhance GABAergic transmission in co-cultured hippocampal
      neurons.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent stem cells
      endowed with neurotrophic potential combined with immunological properties,
      making them a promising therapeutic tool for neurodegenerative disorders.
      However, the mechanisms through which MSCs promote the neurological recovery
      following injury or inflammation are still largely unknown, although cell
      replacement and paracrine mechanisms have been hypothesized. In order to find out
      what are the mechanisms of the trophic action of MSCs, as compared to glial
      cells, on CNS neurons, we set up a co-culture system where rat MSCs (or cortical
      astrocytes) were used as a feeding layer for hippocampal neurons without any
      direct contact between the two cell types. The analysis of hippocampal
      synaptogenesis, synaptic vesicle recycling and electrical activity show that MSCs
      were capable to support morphological and functional neuronal differentiation.
      The proliferation of hippocampal glial cells induced by the release of bioactive
      substance(s) from MSCs was necessary for neuronal survival. Furthermore, MSCs
      selectively increased hippocampal GABAergic pre-synapses. This effect was
      paralleled with a higher expression of the potassium/chloride KCC2 co-transporter
      and increased frequency and amplitude of mIPSCs and sIPSCs. The enhancement of
      GABA synapses was impaired by the treatment with K252a, a Trk/neurotrophin
      receptor blocker, and by TrkB receptor bodies hence suggesting the involvement of
      BDNF as a mediator of such effects. The results obtained here indicate that MSC
      secreted factors induce glial-dependent neuronal survival and trigger an
      augmented GABAergic transmission in hippocampal cultures, highlighting a new
      effect by which MSCs could promote CNS repair. Our results suggest that MSCs may
      be useful in those neurological disorders characterized by an impairment of
      excitation versus inhibition balance.

PMID- 22388099
TI  - Human saliva as a tool to investigate intimate partner violence.

PMID- 22388098
TI  - Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in
      hormone-refractory prostate cancer DU145 cells.
AB  - Pseudolaric acid B (PAB), a natural diterpene acid present in the traditional
      Chinese medicinal herb Tu-Jin-Pi, exerted anticancer effects on various cancer
      cells. However, the effect of PAB on DU145 cells, an in vitro model of hormone
      refractory prostate cancer (HRPC), has not been reported previously. In the
      study, PAB significantly suppressed proliferation of DU145 cells in a dose
      dependent manner without obvious cytotoxicity. IC(50) values of 0.89 +/- 0.18 and
      0.76 +/- 0.15 MUM at 48h was determined by Cell counting kit (CCK-8) assay and
      clone formation assay, respectively. PAB also induced DU145 cells apoptosis as
      confirmed by typical morphological changes and Annexin V-FITC staining.
      Furthermore, we demonstrated that PAB caused a concentration-dependent elevation
      of reactive oxygen species (ROS) level in DU145 cells, and N-acetyl-l-cysteine
      (NAC, a well-known ROS scavenger) could block PAB-induced ROS generation and
      apoptosis. Western blotting and/or caspase activity data indicated that PAB
      downregulated anti-apoptotic Bcl-2 protein and activated caspase-9 and caspase-3,
      which were largely rescued by NAC or MG-132 (proteasome inhibitor). Taken
      together, these findings provide the first evidence that PAB may inhibit growth
      of HRPC DU145 cells and induce apoptosis through ROS generation and Bcl-2
      degradation via the activation of the ubiquitin-proteasome pathway.

PMID- 22388101
TI  - MicroRNA-409-3p regulates cell proliferation and apoptosis by targeting PHF10 in
      gastric cancer.
AB  - Emerging evidence has indicated microRNAs are involved in tumor development and
      progression, acting as tumor suppressors or oncogenes. Here we report that miR
      409-3p was significantly downregulated in gastric cancer (GC) cell lines and
      tissues. Overexpression of miR-409-3p in SGC-7901 gastric cancer cells
      dramatically suppressed cell proliferation and induced cell apoptosis both in
      vitro and in vivo. Furthermore, we demonstrate that the transcriptional regulator
      PHF10 was a target of miR-409-3p. Taken together, these findings suggest that miR
      409-3p may function as a novel tumor suppressor in GC and its anti-oncogenic
      activity may involve the direct targeting and inhibition of PHF10.

PMID- 22388100
TI  - Delineating an epigenetic continuum in head and neck cancer.
AB  - A tissue field of somatic genetic alterations precedes the histopathological
      phenotypic changes of carcinoma. Genomic changes could be of potential use in the
      diagnosis and prognosis of pre-invasive squamous head and neck carcinoma (HNSCC)
      lesions and as markers for cancer risk assessment. Studies of sequential
      molecular alterations and genetic progression of pre-invasive HNSCC have not been
      clearly defined. Studies have shown recurring alterations at chromosome 9p21
      (location of the CDKN2A) and TP53 mutations in the early stages of HNSCC.
      However, gene silencing via hypermethylation is still a relatively new idea in
      the development of HNSCC and little is known about the contribution of
      epigenetics to the development of neoplasia, its transformation, progression, and
      recurrence in HNSCC. This review examines the role of promoter hypermethylation
      of tumor suppressor genes in the progression continuum from benign papillomas to
      malignancy in HNSCC.

PMID- 22388102
TI  - Bax345/BLyS: a novel, completely human fusion protein targeting malignant B cells
      and delivering a unique mitochondrial toxin.
AB  - We generated a fusion protein Bax(345)/BLyS containing the truncated form of Bax
      (Bax(345)) at the N-terminus followed by a 218 linker to the B lymphocyte
      stimulator (BLyS). Bax(345)/BLyS was cytotoxic to a panel of diffuse large B cell
      lymphoma and mantle cell lymphoma lines expressing the BLyS receptors. Specific
      delivery of Bax(345)/BLyS to malignant B cells drove cells into apoptosis by
      mitochondrial dysfunction and treatment of cells with Bax(345)/BLyS induced down
      regulation of Mcl-1, X-IAP, and survivin. Bax(345)/BLyS represents a new class of
      targeted therapeutic agents with a unique mechanism of action and may have
      therapeutic potential for malignant B cells.

PMID- 22388103
TI  - Integrin beta1 mediates epithelial growth factor-induced invasion in human
      ovarian cancer cells.
AB  - Integrins function as cell-extracellular matrix adhesion proteins and have been
      implicated in tumor progression. In ovarian tumors, elevated integrin beta1
      expression correlates with high clinical stage and poor patient survival. In this
      study, we report that EGF treatment up-regulated integrin beta1 mRNA and protein
      levels in ovarian cancer cells. Moreover, pharmacological inhibition of MEK
      totally abolished EGF-induced integrin beta1 up-regulation and cell invasion
      suggesting that MAPK/ERK signaling is required for EGF-induced integrin beta1 up
      regulation and cell invasion. Furthermore, we found that knockdown of integrin
      beta1 expression reduced the intrinsic invasiveness of ovarian cancer cells and
      the EGF-induced cell invasion. Finally, we found that overexpression of integrin
      beta1 was sufficient to promote ovarian cancer cell invasion. This study
      demonstrates that integrin beta1 mediates EGF-induced cell invasion in ovarian
      cancer.

PMID- 22388104
TI  - Recombinant viral capsid protein VP1 suppresses migration and invasion of human
      cervical cancer by modulating phosphorylated prohibitin in lipid rafts.
AB  - Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus inhibits
      invasion/metastasis of cancer cells. Here we studied its mechanism of action on
      human cervical cancer cells. The inhibition of cell invasion by rVP1 was
      accompanied with reduction in phosphatidylinositol (3,4,5)-triphosphate (PIP3),
      phospho-Akt S473, phosphorylated prohibitin (phospho-PHB) T258 in lipid rafts,
      dissociation of phospho-PHB T258 with Raf-1 and the inactivation of Raf-1/ERK.
      Addition of PIP3 or overexpression of constitutively active Akt and raft-anchored
      PHB T258 but not PHB T258I mutant protein reversed the inhibitory effects of
      rVP1. rVP1 inhibited cervical tumor growth and metastasis, and prolonged survival
      in xenograft mouse models. These results suggest that rVP1 inhibits cancer
      metastasis via de-phosphorylation of Akt and PHB T258 in lipid rafts to
      downregulate Raf/ERK signaling.

PMID- 22388107
TI  - Avoiding burnout: the personal health habits and wellness practices of US
      surgeons.
AB  - OBJECTIVE: To evaluate the health habits, routine medical care practices, and
      personal wellness strategies of American surgeons and explore associations with
      burnout and quality of life (QOL). BACKGROUND: Burnout and low mental QOL are
      common among US surgeons and seem to adversely affect quality of care, job
      satisfaction, career longevity, and risk of suicide. The self-care strategies and
      personal wellness promotion practices used by surgeons to deal with the stress of
      practice are not well explored. METHODS: Members of the American College of
      Surgeons were sent an anonymous, cross-sectional survey in October 2010. The
      survey included self-assessment of health habits, routine medical care practices,
      and personal wellness strategies and standardized assessments of burnout and QOL.
      RESULTS: Of 7197 participating surgeons, 3911 (55.0%) participated in aerobic
      exercise and 2611 (36.3%) in muscle strengthening activities, in a pattern
      consistent with the Centers for Disease Control and Prevention recommendations.
      The overall and physical QOL scores were superior for surgeons' following the
      Centers for Disease Control and Prevention recommendations (all P < 0.0001). A
      total of 3311 (46.2%) participating surgeons had seen their primary care provider
      in the last 12 months. Surgeons who had seen their primary care provider in the
      last 12 months were more likely to be up to date with all age-appropriate health
      care screening and had superior overall and physical QOL scores (all P < 0.0001).
      Ratings of the importance of 16 personal wellness promotion strategies differed
      for surgeons without burnout (all P < 0.0001). On multivariate analysis, surgeons
      placing greater emphasis on finding meaning in work, focusing on what is
      important in life, maintaining a positive outlook, and embracing a philosophy
      that stresses work/life balance were less likely to be burned out (all P <
      0.0001). Although many factors associated with lower risk of burnout were also
      associated with achieving a high overall QOL, notable differences were observed,
      indicating surgeons' need to employ a broader repertoire of wellness promotion
      practices if they desire to move beyond neutral and achieve high well-being.
      CONCLUSIONS: This study identifies specific measures surgeons can take to
      decrease burnout and improve their personal and professional QOL.

PMID- 22388106
TI  - Evaluation of clinical outcomes with alvimopan in clinical practice: a national
      matched-cohort study in patients undergoing bowel resection.
AB  - OBJECTIVE: To evaluate in-hospital clinical outcomes after open and laparoscopic
      bowel resection (BR) with or without alvimopan treatment. BACKGROUND: Delayed
      return of gastrointestinal function after BR may be associated with greater
      postoperative morbidity and increased hospital length of stay (LOS). In clinical
      trials, alvimopan--a peripherally acting MU-opioid receptor antagonist-
      accelerated gastrointestinal recovery after open BR. METHODS: A retrospective
      matched-cohort study (NCT01150760) was conducted using a national inpatient
      database. Each alvimopan patient was exact matched (surgical procedure, surgeon
      specialty) and propensity score matched (baseline characteristics) to a
      nonalvimopan BR patient. Outcomes included gastrointestinal and other morbidity
      (cardiovascular, pulmonary, infection, cerebrovascular, thromboembolic);
      mortality; readmission rate; and intensive care unit (ICU) stay (intent-to-treat
      [ITT] population). Postoperative LOS and estimated cost were also compared
      (modified ITT population). RESULTS: Each cohort included 3525 ITT patients with
      similar baseline characteristics. Gastrointestinal (29.8% vs 35.7%) and other
      morbidity (cardiovascular [19.4% vs 24.0%], pulmonary [7.3% vs 10.5%], infectious
      [9.6% vs 11.8%], thromboembolic [1.2% vs 2.1%]), mortality (0.4% vs 1.0%), and
      mean ICU stay (0.3 vs 0.6 days) were lower in the alvimopan group (P <= 0.003 for
      each). Postoperative LOS and estimated direct cost were lower for all alvimopan
      patients and after laparoscopic and open BR (LOS: -1.1, -0.8, and -1.8 days
      respectively; cost: -$2345, -$1382, and -$3218, respectively; P <= 0.0008 for
      each). CONCLUSIONS: On average, alvimopan-treated patients had a lower incidence
      of mortality and most incidents of morbidities. Length of stay, ICU use, and
      estimated cost were also lower with comparable readmissions. These results in
      patients outside the clinical trial setting include laparoscopic colectomy and
      demonstrate a potential association between acceleration of gastrointestinal
      recovery and improved early postoperative outcomes.

PMID- 22388108
TI  - Reliability adjustment for reporting hospital outcomes with surgery.
AB  - BACKGROUND: Reliability adjustment, a novel technique for quantifying and
      removing statistical "noise" from quality rankings, is becoming more widely used
      outside surgery. We sought to evaluate its impact on hospital outcomes assessed
      with the American College of Surgeons' National Surgical Quality Improvement
      Program (ACS-NSQIP). METHODS: We used prospective, clinical data from the ACS
      NSQIP to identify all patients undergoing colon resection in 2007 (n = 181
      hospitals, n = 18,455 patients). We first used standard NSQIP techniques to
      generate risk-adjusted mortality and morbidity rates for each hospital. Using
      hierarchical logistic regression models, we then adjusted these for reliability
      using empirical Bayes techniques. To evaluate the impact of reliability
      adjustment, we first estimated the extent to which hospital-level variation was
      reduced. We then compared hospital mortality and morbidity rankings and outlier
      status before and after reliability adjustment. RESULTS: Reliability adjustment
      greatly diminished apparent variation in hospital outcomes. For risk-adjusted
      mortality, there was a 6-fold difference before (1.4%-7.8%) and less than a 2
      fold difference (3.2% to 5.7%) after reliability adjustment. For risk-adjusted
      morbidity, there was a 2-fold difference (18.0%-38.2%) before and a 1.5-fold
      difference (20.8%-34.8%) after reliability adjustment. Reliability adjustment had
      a large impact on hospital mortality and morbidity rankings. For example, with
      rankings based on mortality, 44% (16 hospitals) of the "best" hospitals (top 20%)
      were reclassified after reliability adjustment. Similarly, 22% (8 hospitals) of
      the "worst" hospitals (bottom 20%) were reclassified after reliability
      adjustment. CONCLUSIONS: Reliability adjustment reduces variation due to
      statistical noise and results in more accurate estimates of risk-adjusted
      hospital outcomes. Given the risk of misclassifying hospitals and surgeons using
      standard approaches, this technique should be considered when reporting surgical
      outcomes.

PMID- 22388109
TI  - The effects of intraoperative hypothermia on surgical site infection: an analysis
      of 524 trauma laparotomies.
AB  - OBJECTIVES: Our primary study objective was to determine whether intraoperative
      hypothermia predisposes patients to postoperative surgical site infections (SSI)
      after trauma laparotomy. BACKGROUND: Although intraoperative normothermia is an
      important quality performance measure for patients undergoing colorectal surgery,
      the effects of intraoperative hypothermia on SSI remain unstudied in trauma.
      METHODS: A review of all patients (July 2003-June 2008) who survived 4 days or
      more after urgent trauma laparotomy at a level I trauma center revealed 524
      patients. Patient characteristics, along with preoperative and intraoperative
      care focusing on SSI risk factors, including the depth and duration of
      intraoperative hypothermia, were evaluated. The primary outcome measure was the
      diagnosis of SSI within 30 days of surgery. Cut-point analysis of the entire
      range of lowest intraoperative temperature measurements established the
      temperature nadir that best predicted SSI development. Single and multiple
      variable logistic regression determined SSI predictors. RESULTS: The mean
      intraoperative temperature nadir of the study population (n = 524) was 35.2
      degrees C +/- 1.1 degrees C and 30.5% had at least 1 temperature measurement less
      than 35 degrees C. Patients who developed SSI (36.1%) had a lower mean
      intraoperative temperature nadir (P = 0.009) and had a greater number of
      intraoperative temperature measurements <35 degrees C (P < 0.001) than those who
      did not. Cut-point analysis revealed an intraoperative temperature of 35 degrees
      C as the nadir temperature most predictive of SSI development. Multivariate
      analysis determined that a single intraoperative temperature measurement less
      than 35 degrees C independently increased the site infection risk 221% per degree
      below 35 degrees C (OR: 2.21; 95% CI: 1.24-3.92, P = 0.007). CONCLUSIONS: Just as
      intraoperative hypothermia is an SSI risk factor in patients undergoing elective
      colorectal procedures, intraoperative hypothermia less than 35 degrees C
      adversely affects SSI rates after trauma laparotomy. Our results suggest that
      intraoperative normothermia should be strictly maintained in patients undergoing
      operative trauma procedures.

PMID- 22388110
TI  - A new era for GPCR research: structures, biology and drug discovery.

PMID- 22388155
TI  - The sustained effects of aripiprazole-augmented clozapine treatment on the
      psychotic symptoms and metabolic profiles of patients with refractory
      schizophrenia.

PMID- 22388156
TI  - Catatonia and encephalopathy associated with paliperidone palmitate.

PMID- 22388157
TI  - Interindividual variation in olanzapine concentration influenced by UGT1A4 L48V
      polymorphism in serum and upstream FMO polymorphisms in cerebrospinal fluid.

PMID- 22388158
TI  - A case of obsessive-compulsive disorder successfully treated with agomelatine
      monotherapy.

PMID- 22388159
TI  - Sapophagia (compulsive soap eating) and attention-deficit/hyperactivity disorder
      in a child responsive to clonidine.

PMID- 22388160
TI  - Comment on "A multicenter, inpatient, phase 2, double-blind, placebo-controlled
      dose-ranging study of LY2140023 monohydrate in patients with DSM-IV
      schizophrenia" by Kinon et al.

PMID- 22388162
TI  - An exploratory, open trial of fluoxetine treatment of juvenile fibromyalgia.

PMID- 22388163
TI  - High venlafaxine serum levels after prior fluoxetine medication.

PMID- 22388164
TI  - Tardive laryngeal dystonia associated with aripiprazole monotherapy.

PMID- 22388165
TI  - Bupropion XL for the sustained treatment of trichotillomania.

PMID- 22388166
TI  - A case of severe hyperthermia after administration of methylphenidate.

PMID- 22388167
TI  - Status epilepticus associated with the administration of long-acting
      methylphenidate in a 7-year-old girl.

PMID- 22388168
TI  - Atomoxetine for encopresis in 2 children with attention-deficit/hyperactivity
      disorder.

PMID- 22388169
TI  - The declining use of reboxetine in years 2000 to 2006: a pharmacoepidemiological
      comparative study.

PMID- 22388170
TI  - Application of external review for subject selection in a schizophrenia trial.

PMID- 22388171
TI  - Scapular kinematics and subacromial-impingement syndrome: a meta-analysis.
AB  - CONTEXT: The literature does not present a consistent pattern of altered scapular
      kinematics in patients with shoulder-impingement syndrome (SIS). OBJECTIVES: To
      perform meta-analyses of published comparative studies to determine the
      consistent differences in scapular kinematics between subjects with SIS and
      controls. In addition, the purpose was to analyze factors of the data-collection
      methods to explain the inconsistencies in reported kinematics. The results of
      this study will help guide future research and enable our understanding of the
      relationship between scapular kinematics and SIS. EVIDENCE ACQUISITION: A search
      identified 65 studies; 9 papers met inclusion criteria. Sample sizes, means, and
      SDs of 5 scapular-kinematic variables were extracted or obtained from each
      paper's lead author. Standard difference in the mean between SIS and controls was
      calculated. Moderator variables were plane of arm elevation, level of arm
      elevation (ARM) and population (POP). EVIDENCE SYNTHESIS: Overall, the SIS group
      had less scapular upward rotation (UR) and external rotation (ER) and greater
      clavicular elevation (ELE) and retraction (RET) but no differences in scapular
      posterior tilt (PT). In the frontal plane, SIS subjects showed greater PT and ER,
      and in the scapular plane, less UR and ER and greater ELE and RET. There was also
      greater ELE and RET in the sagittal plane. There was less UR at the low ARM and
      greater ELE and RET at the high ARM with SIS. Athletes and overhead workers
      showed less UR, while athletes showed greater PT and workers showed less PT and
      ER. The general population with SIS had greater ELE and RET only. CONCLUSIONS:
      Subjects with SIS demonstrated altered scapular kinematics, and these differences
      are influenced by the plane, ARM, and POP. Athletes and overhead workers have a
      different pattern of scapular kinematics than the general population. The
      scapular plane is most likely to demonstrate altered kinematics. These factors
      should be considered when designing futures studies to assess the impact of
      altered kinematics in patients with SIS.

PMID- 22388172
TI  - On the molecular origin of supercapacitance in nanoporous carbon electrodes.
AB  - Lightweight, low-cost supercapacitors with the capability of rapidly storing a
      large amount of electrical energy can contribute to meeting continuous energy
      demands and effectively levelling the cyclic nature of renewable energy sources.
      The excellent electrochemical performance of supercapacitors is due to a
      reversible ion adsorption in porous carbon electrodes. Recently, it was
      demonstrated that ions from the electrolyte could enter sub nanometre pores,
      greatly increasing the capacitance. However, the molecular mechanism of this
      enhancement remains poorly understood. Here we provide the first quantitative
      picture of the structure of an ionic liquid adsorbed inside realistically
      modelled microporous carbon electrodes. We show how the separation of the
      positive and negative ions occurs inside the porous disordered carbons, yielding
      much higher capacitance values (125 F g(-1)) than with simpler electrode
      geometries. The proposed mechanism opens the door for the design of materials
      with improved energy storage capabilities. It also sheds new light on situations
      where ion adsorption in porous structures or membranes plays a role.

PMID- 22388173
TI  - Cancer stem cells and tumor angiogenesis.
AB  - Cancer stem cells (CSCs) have been identified in several human solid and
      hematological tumors. They are able to initiate tumor formation and metastasis
      and express specific cell surface markers. CSC tend to be more resistant to
      chemotherapeutic agents and radiation therapy than more mature cell types from
      the same tissue because of increased expression of antiapoptotic proteins. In
      this context, the development of agents that eliminate or control CSC may be an
      effective strategy for cancer prevention.

PMID- 22388174
TI  - Intracellularly transported adenosine induces apoptosis in [corrected] MCF-7
      human breast cancer cells by accumulating AMID in the nucleus.
AB  - Extracellular adenosine induced apoptosis of MCF-7 human breast cancer cells in a
      concentration (10MUM-10mM)- and treatment time (24-72h)-dependent manner, and the
      effect was inhibited by the adenosine transporter inhibitor dipyridamole, but not
      an inhibitor of adenosine kinase, an inhibitor of AMP-activated protein kinase,
      or inhibitors for A(1), A(2a), A(2b), and A(3) adenosine receptors. No
      significant activation of caspase-7, -8, or -9 was obtained with adenosine.
      Adenosine promoted translocation of apoptosis-inducing factor (AIF)-homologous
      mitochondrion-associated inducer of death (AMID) from the cytosol into the
      nucleus, although the total amount of AMID was not affected. Adenosine-induced
      MCF-7 cell death was abrogated by knocking-down AMID. The results of the present
      study indicate that intracellularly transported adenosine induces MCF-7 cell
      apoptosis by accumulating AMID in the nucleus in a caspase-independent manner.

PMID- 22388175
TI  - Extracellular matrix secreted by reactive stroma is a main inducer of pro
      tumorigenic features on LNCaP prostate cancer cells.
AB  - Tumor microenvironment modifications are related to the generation of reactive
      stroma and to critical events in cancer progression, such as proliferation,
      migration and apoptosis. In order to clarify these cellular interactions mediated
      by reactive stroma, we investigated the effects of cell-cell contacts, and the
      influence of soluble factors and extracellular matrix (ECM) secreted by Benign
      Prostate Hyperplasia (BPH) reactive stroma over LNCaP prostate tumor cells. Using
      in vitro functional assays, we demonstrated that ECM strongly stimulated LNCaP
      cell proliferation and migration, while inhibiting apoptosis, and inducing a
      deregulated expression pattern of several genes related to prostate cancer (PCa)
      progression. Conversely, reactive stromal cells per se and their secreted
      conditioned medium partially modulated these pro-tumorigenic events. These data
      indicate that secreted ECM in reactive stroma microenvironment contains key
      molecules that positively modulate important cancer hallmarks.

PMID- 22388181
TI  - Behavior of natural radionuclides in wastewater treatment plants.
AB  - 56 samples, including influent, primary effluent, secondary effluent and final
      effluent wastewater from two Spanish municipal wastewater treatment plants
      (WWTPs), were analyzed to assess both the occurrence and behavior of natural
      radioactivity during 12 sampling campaigns carried out over the period 2007-2010.
      Influent and final effluent wastewaters were sampled by taking into account the
      hydraulic residence time within the WWTP. A wide range of gross alpha activities
      (15-129 mBq/L) and gross beta activities (477-983 mBq/L) in liquid samples were
      obtained. A correlation analysis between radioactivity in liquid samples and the
      performance characteristics of the WWTPs was performed. The results in liquid
      samples showed that gross beta activities were not influenced by treatment in the
      studied WWTPs. However, gross alpha activities behave differently and an increase
      was detected in the effluent values compared with influent wastewater. This
      behavior was due to the increase in the total dissolved uranium produced during
      secondary treatment. The results indicate that the radiological characteristics
      of the effluents do not present a significant radiological risk and make them
      suitable for future applications.

PMID- 22388182
TI  - Low impact of exposure to environmentally relevant doses of 226Ra in Atlantic cod
      (Gadus morhua) embryonic cells.
AB  - The aim of this study was to investigate whether (226)Ra, a radionuclide present
      in produced water from oil platforms in the North Sea and other offshore drilling
      areas, could affect vulnerable early life stages of Atlantic cod (Gadus morhua).
      Blastula-stage embryonic cells (EC) from fertilized eggs of Atlantic cod were
      isolated and exposed to environmental relevant concentrations of (226)Ra and
      transcription of selected genes quantified. The results showed a weak, but
      significant up-regulation of GPx3 and HSP70 transcripts after 48 h of exposure to
      2.11 Bq/L. In EC exposed to three (226)Ra concentrations (2.11, 23 and 117 Bq/L)
      for 12 h, metallothionein, HSP90AA, thioredoxin and caspase 8 were significantly
      up-regulated in cells exposed to 117 Bq/L, whereas thioredoxin was also
      significantly up-regulated in EC exposed to 23 Bq/L. When EC were exposed to the
      same (226)Ra concentrations for 48 h, only heme oxygenase was significantly up
      regulated in the 23 Bq/L exposure group. The results suggest that environmentally
      relevant activities of (226)Ra may induce oxidative stress and apoptosis in fish
      ECs. Exposure of Atlantic cod EC to Cd, selected as a model toxicant, supported
      the ability of EC around blastula stage to respond to toxicants by altered
      transcription. Due to dilution, environmentally relevant concentrations of
      radionuclides present in produced water would be expected to pose a minor threat
      to early life stages of fish.

PMID- 22388183
TI  - Reporter assays for studying quadruplex nucleic acids.
AB  - DNA and RNA G-quadruplexes have gained increasing attention due to their
      potential role in a wide range of biological functions. The majority of
      functional studies characterize the influence of quadruplexes in gene expression
      including transcription and translation. Many of these studies have used reporter
      assays to elucidate the effect of quadruplexes at certain positions in promoters
      and untranslated mRNA regions (UTRs). Reporter assays are the preferred method to
      ascertain the biological function of DNA or RNA G-quadruplexes intracellularly
      due to their ready availability, fast cloning and experimental setup and
      reproducibility. Moreover, these reporter assays are also helpful to compare or
      screen for selectivity and efficacy of small molecules that target DNA and RNA G
      quadruplexes in the cellular context. Here we briefly discuss various aspects of
      reporter assays followed by a review of available studies using reporter assays
      to understand the role and functions of DNA and RNA quadruplexes in gene
      expression.

PMID- 22388184
TI  - Programmable protein-protein conjugation via DNA-based self-assembly.
AB  - Protein molecules were precisely arrayed on a designable DNA scaffold close to
      each other using a DNA aptamer. By adding a chemical cross-linker, the
      neighboring protein molecules were effectively and covalently cross-linked to
      each other without losing their activities.

PMID- 22388186
TI  - A perspective on imaging cardiovascular disease.

PMID- 22388187
TI  - An improved real-time navigator gating algorithm for reducing motion effects in
      coronary magnetic resonance angiography.
AB  - The phase ordering with automatic window selection (PAWS) algorithm for
      respiratory gating in magnetic resonance imaging is improved by further smoothing
      motion distribution in k-space. This is achieved by requiring that the
      displacement discontinuities in k-space and the range of displacement during the
      acquisition of the center 30% region of k-space are limited to a fraction (1/3 in
      this study) of the gating window. Simulation results and in vivo imaging
      experiments suggest that these modifications reduce the amount of artifacts at a
      reasonable cost of additional scan time as compared to the original PAWS
      algorithm.

PMID- 22388188
TI  - In vivo imaging of vascular gene delivery/expression: Current status.
AB  - Vascular gene therapy is a potential promising treatment for atherosclerotic
      disease. Imaging of vascular gene therapy is essential for the assessment of the
      success of the therapeutic strategy. Several imaging techniques, including MRI,
      ultrasound, and optical imaging, have been evaluated to monitor, enhance, and
      track vascular gene delivery, transfection/transduction, and expression. This
      review summarizes the current status of applying these techniques in the imaging
      of vascular gene therapy.

PMID- 22388189
TI  - Cardiovascular ultrasound imaging - A survey of technical development.
AB  - This article reviews the physics fundamentals in cardiovascular imaging using
      ultrasound and discusses the current technology and advances in clinical
      practices. Challenges in future development are included at the end of the
      article.

PMID- 22388190
TI  - Improved venous suppression on renal MR angiography with recessed elliptical
      centric ordering of K-space.
AB  - PURPOSE: To evaluate recessed elliptical centric ordering of k-space in renal
      magnetic resonance (MR) angiography. METHODS: All imaging was performed on the
      same 1.5 T MR imaging system (GE Signa CVi) using the body coil for signal
      transmission and a phased array coil for reception. Gd, 30 ml, was injected
      manually at 2 ml/sec timed with automatic triggering (SmartPrep). In thirty
      patients using standard elliptical centric ordering, the scanner paused 8 seconds
      between detection of the leading edge of the Gd bolus and initiation of scanning
      beginning with the center of k-space. For the recessed-elliptical centric
      ordering in 20 consecutive patients, this delay was reduced to 4 seconds but the
      absolute center of k-space recessed in by 4 seconds such that in all patients the
      absolute center of k-space was acquired 8 seconds after detecting the leading
      edge of the bolus. On the arterial phase images signal-to-noise ratio (SNR) was
      measured in the aorta, each renal artery and vein and contrast-to-noise ratio
      (CNR) was measured relative to subcutaneous fat. The standard deviation of signal
      outside the patient was considered to be "noise" for calculation of SNR and CNR.
      Incidence of ringing artifact in the aorta and renal veins was noted. RESULTS:
      Aorta SNR and CNR was significantly higher with the recessed technique (p = 0.02)
      and the ratio of renal artery signal to renal vein signal was higher with the
      recessed technique, 4 +/- 2, compared to standard elliptical centric, 3 +/- 2 (p
      = 0.03). Ringing artifact was also reduced with the recessed technique in both
      the aorta and renal veins. CONCLUSION: Gadolinium-enhanced renal MR angiography
      is improved by recessing the absolute center of k-space.

PMID- 22388191
TI  - A preliminary study on adaptive field-of-view tracking in peripheral digital
      subtraction angiography.
AB  - About two million peripheral angiographies are performed annually in the United
      States, hence a reduction in exposure would yield significant healthcare
      benefits. The synchronization of bolus traveling, the table motion, and the
      fluoroscopic imaging chain can be highly effective for dose reduction in Digital
      Subtraction Angiography (DSA) by minimizing the field-of-view according to the
      vascular anatomy of the region traveled by the bolus. The goal of this paper is
      to demonstrate the feasibility of adjusting the field-of-view while tracking the
      contrast bolus, thus reducing the dosage of both the bolus and the radiation. The
      speed of the bolus is respectively estimated in the systole and diastole stages.
      An EKG-gated Hammerstein model is used to predict the bolus chasing speed. A real
      time algorithm is designed to extract the bolus dynamics, and define the field of
      view transversely and longitudinally. A limb stabilization technique is also
      presented to suppress any significant image misalignment. Our simulation results
      show that the proposed techniques are promising for clinical applications.

PMID- 22388192
TI  - Coronary X-Ray angiography and cardiac catheterization.

PMID- 22388193
TI  - Current status of coronary multislice CT angiography.
AB  - Multislice computed tomography (MSCT) is an emerging technique which has an
      enormous potential to improve the current practice of coronary artery imaging.
      This article reviews the current status of coronary MSCT angiography (MSCTA) with
      emphasis on the imaging techniques and clinical utilities of 16-slice CTA.
      Results and experiences gained from coronary MSCTA in the past few years have
      taught us that accurate diagnosis of coronary artery disease relies on good
      technical studies and can be achieved by optimizing image parameters including
      image timing and image reconstruction ECG-trigger delay. Current clinical
      applications of coronary MSCTA include: quantitative assessment of coronary
      artery stenosis, characterization of coronary atherosclerotic plaques, and follow
      up of coronary artery stent and bypass graft. Furthermore, MSCT has brought an
      increasing awareness to the amount of radiation used in CT. This has prompted CT
      researchers and manufacturers to improve various techniques and develop new
      strategies to reduce radiation dose. It is anticipated that MSCT will become a
      sensitive and accurate tool for detecting coronary artery disease and monitoring
      outcomes after treatment for coronary artery disease.

PMID- 22388227
TI  - Smooth pursuit eye movement adaptation in high level gymnasts.
AB  - This study investigated long-term adaptations of smooth pursuit eye movement
      characteristics in high-level gymnasts and compared these responses to those of
      nonathletes. Gymnasts were selected because of their exceptional ability to
      spatially orient during fast, multiaxial whole body rotations. Participants were
      tested with standardized and supra-maximal sinusoidal smooth pursuit
      measurements. The results showed significantly higher gain values in top-level
      gymnasts, followed by young federal team gymnasts, followed by the nonathlete
      control group. By testing participants over the course of three years and also
      after periods of abstinence from training, changes to patterns of smooth pursuit
      over time are revealed. These results have interesting implications for
      understanding the characteristics of eye-movements in expert populations as well
      as understanding the general principles that underlie oculomotor adaptation.

PMID- 22388185
TI  - Targeted polymeric therapeutic nanoparticles: design, development and clinical
      translation.
AB  - Polymeric materials have been used in a range of pharmaceutical and biotechnology
      products for more than 40 years. These materials have evolved from their earlier
      use as biodegradable products such as resorbable sutures, orthopaedic implants,
      macroscale and microscale drug delivery systems such as microparticles and wafers
      used as controlled drug release depots, to multifunctional nanoparticles (NPs)
      capable of targeting, and controlled release of therapeutic and diagnostic
      agents. These newer generations of targeted and controlled release polymeric NPs
      are now engineered to navigate the complex in vivo environment, and incorporate
      functionalities for achieving target specificity, control of drug concentration
      and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this
      optimization of drug pharmacology as aided by careful design of multifunctional
      NPs can lead to improved drug safety and efficacy, and may be complimentary to
      drug enhancements that are traditionally achieved by medicinal chemistry. In this
      regard, polymeric NPs have the potential to result in a highly differentiated new
      class of therapeutics, distinct from the original active drugs used in their
      composition, and distinct from first generation NPs that largely facilitated drug
      formulation. A greater flexibility in the design of drug molecules themselves may
      also be facilitated following their incorporation into NPs, as drug properties
      (solubility, metabolism, plasma binding, biodistribution, target tissue
      accumulation) will no longer be constrained to the same extent by drug chemical
      composition, but also become in-part the function of the physicochemical
      properties of the NP. The combination of optimally designed drugs with optimally
      engineered polymeric NPs opens up the possibility of improved clinical outcomes
      that may not be achievable with the administration of drugs in their conventional
      form. In this critical review, we aim to provide insights into the design and
      development of targeted polymeric NPs and to highlight the challenges associated
      with the engineering of this novel class of therapeutics, including
      considerations of NP design optimization, development and biophysicochemical
      properties. Additionally, we highlight some recent examples from the literature,
      which demonstrate current trends and novel concepts in both the design and
      utility of targeted polymeric NPs (444 references).

PMID- 22388228
TI  - Association between simple renal cysts and development of hypertension in healthy
      middle-aged men.
AB  - OBJECTIVES: The temporal relationship between simple renal cysts and incident
      hypertension is unknown. In this study, we assessed the time-dependent
      relationship between simple renal cysts and incident hypertension in a cohort of
      healthy middle-aged men. METHODS: A cohort study was conducted with data for 4516
      healthy men with no evidence of hypertension at baseline. Study participants
      received a health checkup including abdominal ultrasonography between 2003 and
      2004, and were followed in annual or biennial health examinations until May 2011.
      We matched groups with and without renal cysts by age. RESULTS: Renal cysts were
      found in 123 participants (2.7%). The age-matched control group included 1476
      men. Mean age of the cyst group did not differ from that of the control group
      (42.3 +/- 6.6 and 42.2 +/- 6.8 years, respectively; P = 0.939). SBP was lower in
      the cyst group than in the control group (118.0 +/- 13.2 and 120.5 +/- 12.2,
      respectively; P = 0.044). During 10,731.5 person-years of follow-up, 169
      participants developed hypertension (1.6/100 person-years). Cumulative incidence
      of hypertension was higher in the cyst group than in the control group (29.9 and
      15.4%, respectively; P = 0.000). After adjusting for confounding factors, renal
      cysts still significantly increased risk for hypertension (hazard ratio, 3.28;
      95% confidence interval 2.24-4.80; P = 0.000). Age, BMI, mean arterial pressure
      and a family history of hypertension were also risk factors. CONCLUSION: Simple
      renal cysts independently predicted incident hypertension in this cohort of
      middle-aged men. Further research is justified to test the causal role of renal
      cysts in the development of hypertension.

PMID- 22388229
TI  - Effects of maternal smoking during pregnancy on offspring blood pressure in late
      adolescence.
AB  - OBJECTIVES: Previous studies suggest that maternal smoking during pregnancy is
      associated with elevated offspring blood pressure during childhood. We aimed to
      investigate whether this association remained in late adolescence and, if so,
      whether it could be attributed to an intrauterine effect or to familial
      confounding. METHODS: We used a national cohort of 87,223 young Swedish men born
      between 1983 and 1988 with information on both maternal smoking during pregnancy
      and blood pressure at military conscription. The cohort included 780 full
      brothers discordant for maternal smoking. Generalized estimation equations were
      used to estimate regression coefficients (beta) with 95% confidence intervals
      (95% CIs). RESULTS: We found a small but significant increase in both SBP and DBP
      for young men whose mothers had been daily smokers during pregnancy compared with
      sons of nonsmoking mothers: 0.26 (95% CI 0.09 to 0.44) and 0.45 mmHg (95% CI 0.31
      to 0.59) for SBP and DBP, respectively. In a within-sibling analysis comparing
      full brothers discordant for maternal smoking exposure, point estimates were
      similar but not statistically significant: 0.85 (95% CI -0.19 to 1.90) for DBP
      and 0.81 (-0.56 to 2.19) for SBP. CONCLUSION: Maternal smoking during pregnancy
      is associated with a small but statistically significant increase in offspring
      blood pressure in late adolescence. Because the association does not appear to be
      explained by familial confounding, our results support an intrauterine effect of
      prenatal smoking exposure on blood pressure in late adolescence.

PMID- 22388230
TI  - Longing for clinical excellence: a critical outlook into the NICE recommendations
      on hypertension management--is nice always good?
AB  - The European Society of Hypertension and the European Society of Cardiology have
      started the preparation of the third edition of their joint guidelines on the
      management of arterial hypertension. The authors have focused on the new edition
      of the UK NICE guidelines to learn about the difficulties of disentangling
      evidence from wisdom when preparing recommendations. The two areas where the NICE
      guidelines have changed more importantly are the use of ambulatory blood pressure
      in the diagnosis of hypertension and the choices of antihypertensive agents to
      initiate treatment (less frequent use of diuretics and preference given to
      chlorthalidone and indapamide). NICE recommendations on these topics appear more
      based on opinion than evidence. Strenuous longing for evidence and clinical
      excellence is certainly meritorious, but such a nice approach is not always good.

PMID- 22388232
TI  - Impact of lower range of prehypertension on cardiovascular events in a general
      population:  the Hisayama Study.
AB  - OBJECTIVES: The Seventh Report of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) defined blood
      pressure (BP) levels of 120-139/80-89  mmHg as prehypertension. The objective of
      the present analysis was to examine the impact of prehypertension and its
      population-attributable fraction for development of cardiovascular events in a
      general Japanese population. METHODS: Two thousand, six hundred and thirty-four
      residents of the town of Hisayama aged at least 40 years without cardiovascular
      disease were followed up for 19 years. BP categories were defined using JNC7, and
      prehypertension was divided into the lower (120-129/80-84  mmHg) and higher
      ranges (130-139/85-89  mmHg). During the follow-up period, 449 participants
      developed cardiovascular disease (305 strokes and 187 coronary heart diseases).
      RESULTS: The frequencies of normal BP, prehypertension, and stages 1 and 2
      hypertension were 24.9, 37.7, 23.8, and 13.6%, respectively. The age and sex
      adjusted incidence of cardiovascular disease rose progressively with elevation of
      BP levels (P < 0.001 for trend). The risks of cardiovascular disease in lower and
      higher ranges of prehypertension were 58% [95% confidence interval (CI) 11-126%]
      and 70% (95% CI 18-144%) higher than normal BP even after controlling for other
      cardiovascular risk factors. The population-attributable fraction of
      prehypertension was 13.2%, which was similar to those of stages 1 and 2
      hypertension. CONCLUSIONS: The risks of cardiovascular disease increased
      significantly from the lower range of prehypertension in a general Japanese
      population. Approximately one-third of excess cardiovascular events attributable
      to elevated BP levels were estimated to occur among individuals with
      prehypertension.

PMID- 22388231
TI  - Resistant hypertension and obstructive sleep apnea in the setting of kidney
      disease.
AB  - OBJECTIVES: To explore the relationship between obstructive sleep apnea (OSA) and
      resistant hypertension in chronic kidney disease (CKD) and end-stage renal
      disease (ESRD). METHODS: We examined sleep parameters and blood pressure (BP) in
      224 community-based, non-CKD participants from the Sleep-SCORE study: 88
      nondialysis-dependent CKD and 95 ESRD participants. Unattended home
      polysomnography with standardized scoring protocols and automated BP monitors
      were used. Resistant hypertension was defined as a BP of at least 140/90  mmHg
      despite at least three antihypertensive drugs. RESULTS: Mean SBP of the CKD and
      ESRD groups were significantly higher than that of the non-CKD group [148.2
      (23.8), 144.5 (26.7) vs. 132.2  mmHg (26.7), respectively; P < 0.0001] despite
      the use of more antihypertensive medications. The CKD and ESRD groups had higher
      rates of resistant hypertension than the non-CKD group (41.4, 22.6 vs. 6.7%,
      respectively; P < 0.0001). The severity of sleep apnea was associated with a
      higher risk of resistant hypertension. Although resistant hypertension was
      associated with severe sleep apnea in participants with ESRD [odds ratio (OR)
      7.1, 95% confidence interval (CI) 2.2-23.2), there was no significant association
      in the non-CKD (OR 3.5, 95% CI 0.8-15.4) or CKD groups (OR 1.2, 95% CI 0.4-3.7)
      after accounting for case-mix. CONCLUSION: The association between resistant
      hypertension and sleep apnea appeared robust in ESRD. OSA may contribute to
      resistant hypertension or both may be linked to a common underlying process such
      as volume excess. Future studies in patients with kidney disease should further
      characterize the resistant hypertension-OSA relationship and determine whether
      treatment of underlying mechanisms may improve outcomes.

PMID- 22388233
TI  - The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced
      constriction of renal resistance arteries.
AB  - OBJECTIVES: Increased renal vascular resistance contributes to the pathogenesis
      of hypertension. The new Rho kinase (ROCK) inhibitor SAR407899 more potently
      lowers arterial pressure than the commercially available ROCK inhibitor Y27623.
      We tested whether ROCK inhibition more effectively reduced agonist-induced
      vasoconstriction in renal than in nonrenal resistance arteries and if SAR407899
      more potently inhibits agonist-induced vasoconstriction than Y27632. METHODS: The
      effects of the ROCK inhibitors on endothelin-1 (ET-1) induced vasoconstriction
      were investigated in isolated renal and coronary arteries from lean, normotensive
      Dark Agouti and obese, type 2 diabetic Zucker diabetic fatty (ZDF) rats as well
      as in isolated human resistance arteries from the kidney and thymus. Vascular
      ROCK mRNA abundance was studied by real-time PCR (RT-PCR). RESULTS: ET-1-induced
      constriction depended more on ROCK in rat and human renal resistance arteries
      than in rat coronary or human thymic arteries, respectively. SAR407899 was more
      effective than Y27632 in reducing ET-1-induced vasoconstriction in ZDF rat renal
      resistance arteries. Maximum ET-1-induced vasoconstriction in SAR407899-treated
      and Y27632-treated human renal resistance arteries was 23 +/- 5 and 48 +/- 6% of
      control values, respectively. Transcripts of both ROCK isoforms were detected in
      rat and human renal resistance arteries. In human thymic arteries, only the ROCK2
      transcript was found. CONCLUSION: ET-1-induced vasoconstriction is more ROCK
      dependent in renal than in nonrenal resistance arteries. SAR407899 causes a
      greater inhibition of ET-1-induced vasoconstriction in renal resistance arteries
      from ZDF rats and patients than Y27632. The greater efficacy in renal vessels may
      contribute to the higher antihypertensive potency of SAR407899 compared with
      Y27632.

PMID- 22388234
TI  - An initial reduction in serum uric acid during angiotensin receptor blocker
      treatment is associated with cardiovascular protection:  a post-hoc analysis of
      the RENAAL and IDNT trials.
AB  - OBJECTIVE: Increased levels of serum uric acid (SUA) are thought to be an
      independent risk marker for cardiovascular complications. Treatment with the
      angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs.
      Whether reductions in SUA during ARB therapy are associated with cardiovascular
      protection is unclear. We aimed to investigate this. METHOD: In a post-hoc
      analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus
      with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic
      Nephropathy (IDNT) trials we determined whether the short-term effect of losartan
      and of irbesartan on SUA is related with long-term cardiovascular outcome by
      means of Cox regression. RESULTS: Compared to placebo, losartan significantly
      changed SUA [-0.16  mg/dl; 95% confidence interval (CI) -0.01 to -0.30; P =
      0.031], whereas irbesartan did not (-0.09  mg/dl; (95% CI 0.09 to -0.28; P =
      0.30). Each 0.5  mg/dl decrement in SUA during losartan treatment in the first 6
      months resulted in a reduction in the risk of cardiovascular outcomes by 5.3%
      (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular
      outcomes by 9.2% (95% CI -7.9 to 23.6). Adjustment for the 6-month change in SUA
      attenuated the treatment effect to 4.6% (95% CI -16.2 to 22.0), suggesting that
      part of the cardiovascular protective effect of losartan is attributable to its
      short-term effect on SUA. CONCLUSION: Losartan but not irbesartan significantly
      lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy.
      The degree of reduction in SUA explains part of the cardiovascular effect of
      losartan. This supports the hypothesis that SUA is a modifiable risk factor for
      cardiovascular disease, at least in type 2 diabetics with nephropathy.

PMID- 22388272
TI  - Distribution and turnover of (137)Cs in birch forest ecosystems: influence of
      precipitation chemistry.
AB  - The aim of the present work was to study radioactive caesium in soil and plants
      from birch forests subject to different chemical climate. Four areas and three
      types of precipitation regimes were considered, representing a natural climatic
      range found in Norway: (A) acidic precipitation (southernmost part of the
      country); (B) precipitation rich in "sea salts"/marine cations (coastal areas);
      and (C) + (D) low concentrations of sea salts (inland areas). The results showed
      significant regional differences in plant uptake between the investigated areas.
      For instance the aggregated soil-to-plant transfer coefficients (Tag) were
      generally up to 7-8 times higher for the area receiving acid rain. Differences in
      caesium speciation partly explained the regional variability - e.g. the
      exchangeable fraction ranged from 1 to 40% (with the largest fraction of
      exchangeable caesium found in southernmost Norway). Transfer coefficients
      estimated on the basis of exchangeable fractions showed no significant
      differences between the areas of highest (A) and lowest (C) Tags. However,
      exchangeable fractions taken into consideration, the uptake of (137)Cs in plants
      in the acid rain-influenced area is still about twice that in the sea salt
      influenced area B. A significantly lower concentration of soluble base cations
      and a higher share of acid components in soils in area A is a likely explanation
      for this observation.

PMID- 22388277
TI  - Posaconazole is not superior to itraconazole for fungal prophylaxis in allogeneic
      blood and marrow transplantation.

PMID- 22388278
TI  - Posterior reversible encephalopathy syndrome in a child with post-transplant HHV
      6B encephalitis.

PMID- 22388279
TI  - No evidence for the reversal of adrenal failure after hematopoietic cell
      transplantation in X-linked adrenoleukodystrophy.

PMID- 22388280
TI  - Incidence, characteristics and risk factors of marked hyperbilirubinemia after
      allogeneic hematopoietic cell transplantation with reduced-intensity
      conditioning.
AB  - To analyze the incidence, characteristics and risk factors of hyperbilirubinemia
      after allogeneic hematopoietic cell transplantation with reduced-intensity
      conditioning (allo-RIC), we conducted a retrospective study in three Spanish
      centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92
      patients (20%) developed marked hyperbilirubinemia (>4 mg/day or >68.4 MUM) after
      allo-RIC. The main causes of marked hyperbilirubinemia after transplant were
      cholestasis due to GVHD or sepsis (n=57, 62%) and drug-induced cholestasis (n=13,
      14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver
      biopsy. The most frequent histological finding was iron overload alone (n=6) or
      in combination with other features (n=6). In multivariate analysis, the risk
      factors for marked hyperbilirubinemia after allo-RIC were non-HLA-identical
      sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4-3.6)
      P=0.001), female donors to male recipients (HR 2.1 (95% CI 1.3-3.3) P=0.003) and
      high levels of bilirubin and gamma-glutamyl transpeptidase before transplant (HR
      4.5 (95% CI 2.5-8.4) P<0.001 and HR 4.6 (95% CI 2.6-8.1) P<0.001, respectively).
      Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality
      (HR 1.3 (95% CI 1-1.7), P=0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3-1.7),
      P<0.001) than patients without. In conclusion, we confirm that marked
      hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked
      hyperbilirubinemia after allo-RIC is associated with worse outcome of the
      procedure.

PMID- 22388281
TI  - Serial assessment of toxicity after hematopoietic SCT can discern kinetics of
      transplant-related organ injury and patterns of recovery.

PMID- 22388282
TI  - Anti-host isohemagglutinin production is associated with a higher risk of acute
      GVHD in ABO-incompatible transplantation.
AB  - We retrospectively analyzed the association between anti-host isohemagglutinin
      (IH) production and the development of acute GVHD. Of 189 patients who received
      minor or major/minor ABO-incompatible hematopoietic SCT (HSCT) at our hospital,
      36 patients (19%) showed IH production. IH was detected before the onset of acute
      GVHD in 10, around the same time in 8, and after the onset of acute GVHD in 17
      patients. The cumulative incidence of grade II-IV acute GVHD was significantly
      higher in the IH+ group compared with the IH- group (P<0.0001). The higher risk
      of acute GVHD that was associated with IH production occurred irrespective of
      human leukocyte Ag compatibility and donor type. Furthermore, the incidence of
      acute GVHD in the IH- group was comparable to that seen in major ABO-incompatible
      or -compatible HSCT. Our findings not only showed a strong association between IH
      production and acute GVHD development, but also suggested that IH production
      might be a useful predictor of subsequent acute GVHD after ABO-incompatible HSCT.

PMID- 22388283
TI  - Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney
      disease.
AB  - The present study was designed to identify the changes in microvesicle-dipeptidyl
      peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether
      there were correlations with the severity of diabetic kidney disease (DKD). A
      total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into
      three groups according to the urinary albumin/ creatinine ratio (UACR):
      microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and
      normoalbuminuria group (n = 43), and 34 age- and sex-matched non-diabetic healthy
      subjects were selected as controls. Microvesicle-bound DPP IV and free urinary
      DPP IV were separated by a filtra-centrifugation method. The total microvesicles
      were captured by a specific monoclonal antibody, AD-1. DPP IV activity was
      determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly
      Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels
      were determined by ELISA and Western blot. Our results showed that the
      microvesicle-bound type was the major form of DPP IV in urine; the urinary
      microvesicle-DPP IV excretion of each T2DM group was significantly higher
      compared with controls. The urinary microvesicle-DPP IV level was positively
      correlated with UACR in patients with T2DM. These findings suggest that the
      urinary level of microvesicle-bound DPP IV is associated with the severity of
      DKD.

PMID- 22388286
TI  - Fast gapped-read alignment with Bowtie 2.
AB  - As the rate of sequencing increases, greater throughput is demanded from read
      aligners. The full-text minute index is often used to make alignment very fast
      and memory-efficient, but the approach is ill-suited to finding longer, gapped
      alignments. Bowtie 2 combines the strengths of the full-text minute index with
      the flexibility and speed of hardware-accelerated dynamic programming algorithms
      to achieve a combination of high speed, sensitivity and accuracy.

PMID- 22388287
TI  - TULIPs: tunable, light-controlled interacting protein tags for cell biology.
AB  - Naturally photoswitchable proteins offer a means of directly manipulating the
      formation of protein complexes that drive a diversity of cellular processes. We
      developed tunable light-inducible dimerization tags (TULIPs) based on a synthetic
      interaction between the LOV2 domain of Avena sativa phototropin 1 (AsLOV2) and an
      engineered PDZ domain (ePDZ). TULIPs can recruit proteins to diverse structures
      in living yeast and mammalian cells, either globally or with precise spatial
      control using a steerable laser. The equilibrium binding and kinetic parameters
      of the interaction are tunable by mutation, making TULIPs readily adaptable to
      signaling pathways with varying sensitivities and response times. We demonstrate
      the utility of TULIPs by conferring light sensitivity to functionally distinct
      components of the yeast mating pathway and by directing the site of cell
      polarization.

PMID- 22388290
TI  - Modified fast marching and level set method for medical image segmentation.
AB  - In this paper, an interactive segmentation method that combines fast marching and
      level set method is proposed. Level set segmentation involves solving the energy
      based active contour minimization problems by the computation of geodesics or
      minimal distance curves. First, by selecting the seed point, the fast marching
      method is used to extract rough boundaries of the interested object. We modified
      the traditional fast marching method to capture the weak edges by introducing
      watershed transform. Then, the contour obtained from the fast marching method
      mentioned above is regarded as an initialization and the level set method is used
      to finely tune the contour. The algorithm is demonstrated on some medical images:
      segmentation of knee tissues in CT image and segmentation of brain tissues in MR
      image. The results show that this method can remove the small regions obtained
      from fast marching method and converge the desired boundary.

PMID- 22388289
TI  - Computerized video analysis of social interactions in mice.
AB  - The study of social interactions in mice is used as a model for normal and
      pathological cognitive and emotional processes. But extracting comprehensive
      behavioral information from videos of interacting mice is still a challenge. We
      describe a computerized method and software, MiceProfiler, that uses geometrical
      primitives to model and track two mice without requiring any specific tagging.
      The program monitors a comprehensive repertoire of behavioral states and their
      temporal evolution, allowing the identification of key elements that trigger
      social contact. Using MiceProfiler we studied the role of neuronal nicotinic
      receptors in the establishment of social interactions and risk-prone postures. We
      found that the duration and type of social interactions with a conspecific
      evolves differently over time in mice lacking neuronal nicotinic receptors
      (Chrnb2-/-, here called beta2(-/-)), compared to C57BL/6J mice, and identified a
      new type of coordinated posture, called back-to-back posture, that we rarely
      observed in beta2(-/-) mice.

PMID- 22388288
TI  - Long-term, efficient inhibition of microRNA function in mice using rAAV vectors.
AB  - Understanding the function of individual microRNA (miRNA) species in mice would
      require the production of hundreds of loss-of-function strains. To accelerate
      analysis of miRNA biology in mammals, we combined recombinant adeno-associated
      virus (rAAV) vectors with miRNA 'tough decoys' (TuDs) to inhibit specific miRNAs.
      Intravenous injection of rAAV9 expressing anti-miR-122 or anti-let-7 TuDs
      depleted the corresponding miRNA and increased its mRNA targets. rAAV producing
      anti-miR-122 TuD but not anti-let-7 TuD reduced serum cholesterol by >30% for 25
      weeks in wild-type mice. High-throughput sequencing of liver miRNAs from the
      treated mice confirmed that the targeted miRNAs were depleted and revealed that
      TuDs induced miRNA tailing and trimming in vivo. rAAV-mediated miRNA inhibition
      thus provides a simple way to study miRNA function in adult mammals and a
      potential therapy for dyslipidemia and other diseases caused by miRNA
      deregulation.

PMID- 22388291
TI  - A description for computed tomography based on sinusoidal curves.
AB  - A new description for computed tomography, parallel and equal to Radon
      transformation but based on sinusoidal functions rather than line integrals, is
      introduced. This representation contributes an effective algorithm to reduce
      metal artefacts in reconstruction. Using this method, the information included in
      the scan data corresponding to the metal implants can be separated from the
      original projection, an amending method rather than interpolation is therefore
      provided to reach higher accuracy for reconstruction. The method is with low
      complexity in computation, and can be combined online with filtered
      backprojection (FBP), which is the most widely used algorithm in practice, to
      improve the quality of the reconstructed image. Also, the method has the
      potential to deal with the artefacts caused by beam hardening and partial volume,
      and to be developed into a straight reconstruction algorithm based on the
      sinusoidal representation. Examples are presented for clearer description and
      demonstration.

PMID- 22388292
TI  - Attenuation characteristics of fiberoptic plates for digital mammography and
      other X-ray imaging applications.
AB  - Spatially coherent fiberoptic plates are important components of some charge
      coupled device (CCD)-based x-ray imaging systems. These plates efficiently
      transmit scintillations from the phosphor, and also filter out x-rays not
      absorbed by the phosphor, thus protecting the CCD from direct x-ray interaction.
      The thickness of the fiberoptic plate and the CCD package present a significant
      challenge in the design of a digital x-ray cassette capable of insertion into the
      existing film-screen cassette holders of digital mammography systems. This study
      was performed with an aim to optimize fiberoptic plate thickness. Attenuation
      measurements were performed on nine fiberoptic plates varying in material
      composition that exhibit desirable optical characteristics such as good coupling
      efficiency. Mammographic spectra from a clinical mammographic system and an
      Americium-241 (Am-241) source (59.54 KeV) were used. The spectra were recorded
      with a high-resolution cadmium zinc telluride (CZT)-based spectrometer and
      corrected for dead time and pile-up. The linear attenuation coefficients varied
      by a factor of 3 in the set of tested fiberoptic plates at both mammographic
      energies and 59.54 keV. Our results suggest that a 3-mm thick high-absorption
      plate might provide adequate for shielding at mammographic energies. A thickness
      of 2-mm is feasible for mammographic applications with further optimization of
      the fiberoptic plate composition by incorporating non-scintillating, high-atomic
      number material. This would allow more space for cooling components of the
      cassette and for a more compact device, which is critical for clinical
      implementation of the technology.

PMID- 22388293
TI  - A pilot investigation of new superparamagnetic iron oxide (ferumoxytol) as a
      contrast agent for cardiovascular MRI.
AB  - PURPOSE: To evaluate the imaging potential of ferumoxytol, a new
      superparamagnetic iron oxide colloidal blood pool contrast agent. MATERIALS AND
      METHODS: Magnetic resonance (MR) imaging at 1.5 Tesla was performed before and
      after intravenous injection of ferumoxytol using escalating doses of 0.4, 0.8,
      1.2 and 1.6 mg Fe/kg for a total of 4 mg Fe/kg in five subjects imaged with 3D MR
      Angiography (MRA) of the trifurcation after each dose. In five subjects cardiac
      cine MRI was performed pre and post 4.0 mg Fe/kg. Image quality was assessed by
      measuring signal to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the
      vascular structures. Pre- and post-dose urine and blood tests as well as
      EKG/vital sign monitoring were performed to evaluate safety and blood samples
      were collected for T1 relaxivity measurements. RESULTS: Cumulative doses of 0,
      0.4, 1.2, 2.4 and 4 mg Fe/kg yielded mean SNR in the arteries of 10, 16, 39, 57
      and 69 respectively indicating that the higher doses produced higher SNR on 3D
      vascular images. Similarly aorta SNR on 2D time-of-flight increased from 11.8
      without Fe to 15.4 post Fe (p = 0.004) indicating improved image quality on MRA
      sequences optimized for use without contrast. At 4 mg Fe/kg there was a
      substantial T1 shortening measured in the blood from 1990 +/- 573 ms to 80 +/- 42
      ms (p < 0.0001), corresponding to the increased SNR. Images of large vascular
      structures including cardiac chambers, aorta, and pulmonary arteries were
      excellent post ferumoxytol but images of smaller arteries of the trifurcation
      were difficult to evaluate due to enhancement of the overlapping veins. No
      serious adverse events occurred. CONCLUSION: The new superparamagnetic iron oxide
      colloid ferumoxytol is a promising blood pool agent especially for cardiac, aorta
      and pulmonary imaging.

PMID- 22388294
TI  - Automatic segmentation of contrast-enhanced time resolved image series.
AB  - Medical imaging often involves the injection of contrast agents and the
      subsequent analysis of tissue enhancement patterns. Many important types of
      tissue have characteristic enhancement patterns; for example, in MR mammography,
      malignancies exhibit a characteristic "wash out" temporal pattern, while in MR
      angiography, arteries, veins and parenchyma each have their own distinctive
      temporal signature. In such time resolved image series, there are substantial
      changes in intensities; however, this change is due primarily to the contrast
      agent, rather than to motion. As a result, the task of automatically segmenting
      contrast-enhanced images poses interesting new challenges. In this paper, we
      propose a new image segmentation algorithm for time resolved image series with
      contrast enhancement, using a model-based time series analysis of individual
      pixels. We take an energy minimization approach to ensure spatial coherence. The
      energy is minimized in an expectation-maximization fashion that alternates
      between segmenting the image into a number of non-overlapping regions and finding
      the temporal profile parameters which describe the behavior of each region.
      Preliminary experiments on MR angiography and MR mammography studies show the
      algorithm's ability to find an accurate segmentation.

PMID- 22388296
TI  - Net clinical benefit of prehospital glycoprotein IIb/IIIa inhibitors in patients
      with ST-elevation myocardial infarction and high risk of bleeding: effect of
      tirofiban in patients at high risk of bleeding using CRUSADE bleeding score.
AB  - AIMS: The aim of this subanalysis was to assess the net clinical effect of
      prehospital administration of tirofiban in ST-elevation myocardial infarction
      (STEMI) patients with high risk of bleeding. METHODS: This is a retrospective
      subanalysis of the On- TIME 2 trial, a multicenter, controlled randomized trial
      of the effects of high bolus-dose tirofiban given in the ambulance in STEMI
      patients. Tirofiban was given on top of aspirin, heparin, and clopidogrel.
      According to CRUSADE, patients with a moderate to very high baseline risk of
      bleeding were defined as high risk and patients with a very low or low baseline
      bleeding risk were defined as low risk. Primary endpoint was net adverse clinical
      events (NACE) at 30 days (defined as the combined incidence of death, recurrent
      myocardial infarction, urgent target vessel revascularization, stroke, or non
      coronary artery bypass graft [CABG]-related major bleeding). RESULTS: Of 1309
      patients, a high bleeding risk was present in 291 patients (22.2%). In these high
      risk bleeding patients, tirofiban significantly improved after percutaneous
      coronary intervention (PCI) ST-segment resolution. Administration of tirofiban in
      high-risk bleeding patients showed no difference in 30-day major adverse cardiac
      events (MACE) (9.4% vs 13.0%; P=.330; relative risk [RR], 0.72; 95% confidence
      interval [CI], 0.37-1.39). However, pretreatment with tirofiban was associated
      with a nonsignificant increase in non-CABG related bleeding (8.6% vs 3.6%;
      P=.082; RR, 2.38; 95% CI, 0.90-6.39). The net clinical effect (30-day NACE) of
      tirofiban in this group was balanced (11.5% vs 15.2%; P=.365; RR, 0.76; 95% CI,
      0.41-1.38). CONCLUSION: Prehospital use of tirofiban in STEMI patients with high
      risk of bleeding improves post-PCI ST-segment resolution, but increases
      nonsignificantly the risk of non-CABG related bleeding. The net result is a
      balanced effect on 30-day NACE. Additional studies should clarify how use of
      bleeding risk scores should modify medical (antiplatelet) therapy.

PMID- 22388297
TI  - Different spectrum of vascular complications after angio-seal deployment or
      manual compression.
AB  - BACKGROUND: Reported complication rates after vascular closure device deployment
      or femoral manual compression (MC) are similar. However, the features and
      severity of such complications have never been thoroughly evaluated. METHODS AND
      RESULTS: A consecutive series of 1241 patients treated from 2008 to 2010 with
      Angio-Seal (AS) was prospectively evaluated for vascular complications (VC). As
      control group, we used a consecutive series of 672 patients treated with MC in
      the 7 months preceding AS adoption at our institution. VC were observed in 88
      patients, 55 with AS and 33 with MC (relative risk, 0.90; 95% confidence
      interval, 0.59-1.38; P=.63). The clinical profile of complications observed in
      the 2 groups was different. Groin hematomas were more frequent with MC (100% vs
      65.5%; P=.0005) and retroperitoneal bleedings were more common with AS (41.8% vs
      6.1%; P=.0005). AS complications required more frequently transfusions (49.1% vs
      18.2%; P=.006), while MC complications significantly delayed hospital discharge,
      in comparison to AS (4.3 +/- 4.0 days vs 2.7 +/- 1.9 days; P=.01). Differences in
      groin hematoma and retroperitoneal bleeding rates were confirmed after propensity
      score matching. Finally, a different allocation of diagnostic/therapeutic
      resources was observed in the 2 groups. CONCLUSION: AS and MC were associated
      with similar incidences of VC, with a higher prevalence of severe complications
      (retroperitoneal hemorrhages and transfusions) after using AS. However,
      complications after MC were associated with significantly prolonged hospital
      stay. Comparison between different hemostatic strategies should consider the
      logistic burden imposed by different vascular complications.

PMID- 22388298
TI  - Balancing the yin and the yang of vascular closure.

PMID- 22388295
TI  - Intrinsic therapeutic applications of noble metal nanoparticles: past, present
      and future.
AB  - Biomedical nanotechnology is an evolving field having enormous potential to
      positively impact the health care system. Important biomedical applications of
      nanotechnology that may have potential clinical applications include targeted
      drug delivery, detection/diagnosis and imaging. Basic understanding of how
      nanomaterials, the building blocks of nanotechnology, interact with the cells and
      their biological consequences are beginning to evolve. Noble metal nanoparticles
      such as gold, silver and platinum are particularly interesting due to their size
      and shape dependent unique optoelectronic properties. These noble metal
      nanoparticles, particularly of gold, have elicited a lot of interest for
      important biomedical applications because of their ease of synthesis,
      characterization and surface functionalization. Furthermore, recent
      investigations are demonstrating another promising application of these
      nanomaterials as self-therapeutics. To realize the potential promise of these
      unique inorganic nanomaterials for future clinical translation, it is of utmost
      importance to understand a few critical parameters; (i) how these nanomaterials
      interact with the cells at the molecular level; (ii) how their biodistribution
      and pharmacokinetics influenced by their surface and routes of administration;
      (iii) mechanism of their detoxification and clearance and (iv) their therapeutic
      efficacy in appropriate disease model. Thus in this critical review, we will
      discuss the various clinical applications of gold, silver and platinum
      nanoparticles with relevance to above parameters. We will also mention various
      routes of synthesis of these noble metal nanoparticles. However, before we
      discuss present research, we will also look into the past. We need to understand
      the discoveries made before us in order to further our knowledge and
      technological development (318 references).

PMID- 22388299
TI  - Steroids for the prevention of restenosis in bare-metal stents--a systematic
      review and meta-analysis.
AB  - INTRODUCTION: Stent restenosis remains a common complication of bare-metal stent
      (BMS) implantation. Even in the drug-eluting stent (DES) era, there remains a
      significant proportion of patients who may not be eligible for DES due to
      inability to comply with prolonged dual antiplatelet therapy. We reviewed the
      validity of empirical evidence that periprocedural treatment with steroids at the
      time of insertion of a BMS may delay restenosis and provide benefit through
      reductions in adverse clinical events. METHODS: We searched the PubMed, EMBASE
      and Cochrane Central Register of Controlled Trials databases for randomized
      controlled trials conducted between 1990 and 2011 that assessed the impact of
      systemic steroid administration within 72 hours to 7 days of angioplasty alone
      and BMS placement. The comparator included standard medical therapy and/or
      placebo. Outcomes assessed were: (1) rates of restenosis at the end of at least 6
      months of follow-up; (2) rates of target vessel revascularization; and (3) risk
      of all-cause mortality. The methodological quality of the studies was assessed,
      as was publication bias. Relative risk of restenosis, revascularization, and
      rates of in-hospital mortality for treatment and control groups were compared
      using a random effects model (Mantel- Haenszel). RESULTS: We identified 5 studies
      that met inclusion criteria. No significant reduction in restenosis rates was
      observed after angioplasty alone with steroids. However, with BMS, significant
      reductions in restenosis rates (relative risk [RR], 0.60; 95% confidence interval
      [CI], 0.37-0.97; P=.04), and target vessel revascularization rates (RR, 0.56; 95%
      CI, 0.34-0.92; P=.02) were observed in the steroid-treated group. A 28% mortality
      reduction was observed with steroid treatment with BMS placement, but was not
      statistically significant. CONCLUSION: Periprocedural steroid administration
      during BMS implantation may reduce rates of restenosis and target vessel
      revascularization, without adverse clinical effects attributable to steroid use.

PMID- 22388300
TI  - Gender-based analysis of the 3-year outcome of bioactive stents versus paclitaxel
      eluting stents in patients with acute myocardial infarction: an insight from the
      TITAX-AMI trial.
AB  - BACKGROUND: The TITAX-AMI trial demonstrated a better clinical outcome of
      titanium-nitride-oxide-coated bioactive stents (BAS) as compared with paclitaxel
      eluting stents (PES) in patients with acute myocardial infarction (MI) undergoing
      early percutaneous coronary intervention (PCI). We explored the gender-based 3
      year outcome of BAS as compared with PES in a subgroup analysis of the TITAX-AMI
      trial. METHODS: A total of 214 patients (52 women) with acute MI were randomly
      assigned to BAS, and 211 patients (54 women) to PES. The primary endpoint was
      major adverse cardiac events (MACE) including cardiac death, recurrent MI, and
      target lesion revascularization (TLR). Secondary endpoints were all-cause death,
      a composite of cardiac death or recurrent MI, and stent thrombosis (ST). RESULTS:
      Women were older and had smaller reference vessel diameter (P<.001 for both) as
      compared with men. At 3-year follow-up, both MACE and TLR showed a trend to be
      higher in women as compared with men (24.5% versus 16.3% [P=.059] and 15.1%
      versus 8.8% [P=.065], respectively). The rate of all-cause death was
      significantly higher in women as compared with men (13.2% versus 6.0%,
      respectively; P=.02). Among female patients, MACE, cardiac death, recurrent MI,
      TLR, and ST were all statistically similar between the two stent groups (P>.05
      for all). CONCLUSIONS: In the current post hoc gender-based analysis of the TITAX
      AMI trial, the 3-year outcome of patients undergoing PCI for acute MI was
      slightly worse in female patients as compared with their male counterparts, as
      reflected by a trend toward a higher primary composite endpoint of MACE and TLR.

PMID- 22388301
TI  - Outcomes in contemporary coronary interventions with drug-eluting stents for
      acute myocardial infarction: the gender role.

PMID- 22388302
TI  - In vivo comparison of Fourier-domain optical coherence tomography and
      intravascular ultrasonography.
AB  - BACKGROUND: We sought to evaluate the findings of Fourier-domain optical
      coherence tomography (FD-OCT) and intravascular ultrasonography (IVUS) used for
      the in vivo assessment of coronary lesions. METHODS: We identified 19 lesions in
      15 patients undergoing percutaneous coronary intervention that were assessed by
      both FD-OCT and IVUS and compared the lumen area and maximum/minimum lumen
      diameter at the site of maximum stenosis and the proximal and distal reference
      cross-sections. RESULTS: At the site of maximum stenosis, excellent correlation
      was found between FD-OCT and IVUS measurements: minimum lumen area (3.80 +/- 2.36
      mm2 and 4.60 +/- 2.13 mm2, respectively; P=.002; Spearman's rho = 0.94), maximum
      lumen diameter (2.30 +/- 0.79 mm and 2.54 +/- 0.60 mm, respectively; P=.005;
      Spearman's rho = 0.93), and minimum lumen diameter (1.89 +/- 0.69 mm and 2.24 +/-
      0.54 mm, respectively; P=.0001; Spearman's rho = 0.90). Weaker correlations were
      found between FD-OCT and IVUS measurements of the proximal reference lumen area
      (4.74 +/- 1.86 mm2 and 5.16 +/- 2.10 mm2, respectively; P=.33; Spearman's rho =
      0.76) and distal reference lumen area (5.14 +/- 1.60 mm2 and 5.47 +/- 2.45 mm2,
      respectively; P=.144; Spearman's rho = 0.72). CONCLUSIONS: Excellent correlation
      was found in FD-OCT and IVUS luminal measurements at the site of maximum coronary
      stenosis with weaker correlation at the proximal and distal reference cross
      sections. FD-OCT minimum lumen area measurements were smaller than the IVUS
      measurements.

PMID- 22388303
TI  - Optical coherence tomography evaluation of in-stent restenotic lesions with
      visible microvessels.
AB  - OBJECTIVE: We sought to evaluate the characteristics of in-stent restenosis (ISR)
      lesions with microvessels, detected by an optical coherence tomography (OCT).
      BACKGROUND: No sufficient in vivo data exist regarding microvessel
      characteristics in ISR lesions. METHODS: Among 78 ISR lesions (drug-eluting
      stent, n = 72; bare-metal stent, n = 6) in our OCT registry database, visible
      microvessels were detected in 21 (27%). Microvessels were defined as low
      backscattering structures <200 MUm in diameter on OCT. Clinical, angiographic,
      and OCT findings were compared between lesions with and without microvessels.
      RESULTS: Lesions with microvessels had a larger reference vessel diameter (2.90
      +/- 0.47 mm vs 2.58 +/- 0.42 mm; P=.009) and post-stent minimum lumen diameter
      (2.76 +/- 0.29 mm vs 2.54 +/- 0.39 mm; P=.033) than those without microvessels.
      From OCT findings at the segment with minimal lumen cross-sectional area (CSA),
      neointimal hyperplasia (NIH) CSA (5.4 +/- 1.7 mm2 vs 4.2 +/- 2.1 mm2; P=.024) and
      percent NIH CSA (NIH CSA x 100/stent CSA) were significantly greater in lesions
      with microvessels (79 +/- 12% vs 67 +/- 16%; P=.001). On multivariate analysis,
      reference vessel diameter (odds ratio [OR], 4.64; 95% confidence interval [CI],
      1.05-20.4; P=.043) and percent NIH CSA at the segment with minimal lumen CSA (OR,
      1.06; 95% CI, 1.01-1.12; P=.021) were independent predictors of microvessels.
      From receiver operating characteristic analysis, the cut-off values of reference
      vessel diameter and percent NIH CSA predicting the presence of microvessels were
      3.1 mm and 74%, respectively. CONCLUSIONS: Visible microvessels in ISR lesions
      might be associated with increased vessel size and extent of NIH.

PMID- 22388305
TI  - Preventing spasm during transradial angiography: sometimes less is more.

PMID- 22388304
TI  - Nitroglycerin plus diltiazem versus nitroglycerin alone for spasm prophylaxis
      with transradial approach.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy of nitroglycerin
      and diltiazem versus nitroglycerin alone in preventing radial artery spasm (RAS)
      during transradial coronary procedures. BACKGROUND: Spasm after transradial
      access decreases procedural success. Multiple spasmolytics are used to prevent
      spasm. Individual efficacy of these agents is not conclusively established.
      METHODS: One hundred and fifty patients undergoing coronary procedures through
      radial artery were enrolled and divided into two groups of 75 patients each.
      Patients in Group A received 200 MUg nitroglycerin plus 2.5 mg diltiazem intra
      arterially, and group B patients received 200 MUg nitroglycerin plus placebo
      (saline). Blood pressure (BP) and heart rate (HR) were recorded at baseline and
      for 5 minutes after cocktail was given. Clinical signs of RAS, such as pain and
      resistance during catheter maneuver, were recorded in both groups during the
      procedure. RESULTS: Systolic and diastolic BP decreased significantly in Group A
      compared to Group B after cocktail was given (P<.001 and P<.022, respectively).
      There were no significant changes of HR in either group. There was no significant
      difference in the incidence of clinical RAS between Group A (diltiazem plus
      nitroglycerin) versus Group B (nitroglycerin alone) (5% vs 7%; P=1.000).
      Furthermore, we found higher incidence of local burning pain in the forearm in
      patients that receive intra-arterial diltiazem plus nitroglycerin compared to
      nitroglycerin alone (21% vs 9%; P=.041). CONCLUSION: Diltiazem plus nitroglycerin
      showed no advantage compared to nitroglycerin alone in prevention of RAS in
      transradial approach.

PMID- 22388306
TI  - Myocardial and pericardial staining by transradial Optitorque Jacky shape
      catheter during left ventriculogram.
AB  - A 69-year-old male presented with inferior wall ischemia. Transradial coronary
      angiogram with an Optitorque Jacky shape catheter showed unobstructed coronary
      arteries (Terumo Medical Corporation). Left ventriculography was complicated with
      myocardial and pericardial contrast staining. The catheter was pulled back. The
      patient experienced sharp chest pain that resolved in 20 minutes. Stat
      transthoracic echocardiogram was unremarkable. The patient remained
      hemodynamically stable. Transthoracic echocardiogram the next morning revealed
      trivial pericardial effusion. Patient was asymptomatic on outpatient follow-up.
      The Optitorque transradial catheter, with Jacky and Tiger tip shapes, is the
      preferred multipurpose catheter for transradial coronary angiogram. Potential
      complications of ventriculogram catheters are myocardial staining, myocardial
      rupture, cardiac tamponade, and arrhythmias caused by improper position of the
      catheter tip. It is imperative to check the position of the catheter tip with a
      small amount of contrast injection prior to left ventriculography (even though we
      checked our position with a small test injection) to avoid these types of
      complication. This case illustrates the value of careful manipulation and
      placement of transradial catheter during left ventriculography.

PMID- 22388307
TI  - Collateral myocardial blush in inferior wall myocardial infarction: a new
      diagnostic tool to differentiate between occluded right coronary and circumflex
      arteries.
AB  - OBJECTIVES: The infarct-related artery (IRA) in inferior wall myocardial
      infarction (IMI) may be problematic to identify due to occasional instances in
      which the right coronary (RCA) and left circumflex (CX) arteries are both
      occluded. We sought to investigate if impaired collateral myocardial blush (CMBG)
      identifies the correct IRA. METHODS: Between 2002 and 2010, we retrospectively
      analyzed 1907 patients who underwent primary angioplasty at our institution. Of
      these, 44 had an IMI together with total occlusion of both the RCA and CX.
      RESULTS: Thirty of these had good collaterals to both distal vessels. Ten of this
      group had impaired CMBG, indicating the IRA. In 2 patients, angioplasty was
      attempted in the wrong artery in retrospect. CONCLUSIONS: The correct IRA may be
      difficult to identify in patients with IMI and occlusion of both RCA and CX
      arteries. Impaired CMBG is a new tool to aid in this challenge.

PMID- 22388308
TI  - Cardiac resynchronization therapy improved heart failure after left bundle branch
      block during transcatheter aortic valve implantation.
AB  - After transcatheter aortic valve implantation (TAVI) in a 75-year-old male,
      chronic wide left bundle branch block (LBBB) developed. He experienced repeated
      episodes of decompensated systolic heart failure with severe systolic left
      ventricular dysfunction. After cardiac resynchronization therapy, his heart
      function improved substantially and he had no further admissions for heart
      failure. Cardiac resynchronization therapy can be effective in systolic heart
      failure associated with LBBB developing after TAVI.

PMID- 22388309
TI  - Percutaneous repair of anterior mitral leaflet perforation.
AB  - A 59-year-old male underwent coronary artery bypass grafting and mitral ring
      annuloplasty 4 years ago. The procedure was complicated by sternal wound
      infection. Recently, he presented with multiple admissions for decompensated
      heart failure with volume overload and pulmonary edema. He was found to have
      severe mitral regurgitation (MR) and transesophageal echocardiography (TEE)
      demonstrated severe MR through an anterior mitral leaflet perforation. Due to
      high surgical risk, he was referred for transcatheter repair of his mitral valve.
      This case illustrates the first reported use of an Amplatzer atrial septal
      occluder device for percutaneous mitral leaflet repair using three-dimensional
      TEE guidance after prior surgical mitral ring annuloplasty repair.

PMID- 22388310
TI  - Tumor blush: left ventricular cardiac hemangioma with supply from both the left
      anterior descending and circumflex arteries.
AB  - A fifty-year-old male had an echocardiogram for an abnormal electrocardiogram; it
      revealed a left ventricular mass. A cardiac catheterization revealed normal
      coronary arteries and a fine tumor blush of the cardiac tumor with feeding
      arteries from the circumflex as well as the second diagonal coronary vessels. Due
      to increased risk of embolization, he underwent surgery via a transatrial
      approach and a 1.5 cm cavernous-capillary hemangioma was removed from the base of
      the posteromedial papillary muscle. Primary tumors of the heart are rare, and the
      symptoms and signs depend on the location and size of the tumor. Coronary
      angiography remains an integral part in the evaluation of cardiac tumors and
      often can reveal a characteristic 'tumor blush.' The natural history of the tumor
      is unpredictable and excision of the tumor remains the treatment of choice. We
      present a rare case of characteristic angiographic tumor blush of a left
      ventricular cardiac hemangioma with feeding arteries from both the left anterior
      descending as well as the circumflex arteries. This rare two-system supply was
      due to the intracavitary location of the hemangioma, and fortunately did not pose
      any excessive difficulty in mobilization and excision during surgery.

PMID- 22388311
TI  - Tumor blush in primary cardiac tumors.

PMID- 22388312
TI  - Guide catheter suction with novel double wire technique for successful management
      of large thrombus in occluded right coronary artery.
AB  - Patients with large intracoronary thrombi represent a difficult management
      problem for the interventional cardiologist. Deep guide catheter engagement and
      thrombus aspiration have been described but are associated with serious risk of
      dissection and vessel closure. We describe here thrombus aspiration using a guide
      catheter with novel double wire technique to achieve rapid reperfusion of the
      coronary artery while avoiding possible complications associated with the
      technique.

PMID- 22388313
TI  - Multiple coronary artery thrombosis in a 41-year-old male patient presenting with
      ST-segment elevation myocardial infarction.
AB  - Simultaneous occlusion of multiple epicardial coronary arteries is an uncommon
      finding in patients presenting with ST-segment elevation myocardial infarction
      (STEMI). We describe a 41- year-old male Asian patient who presented with
      inferior and anterior STEMI complicated by cardiogenic shock and frequent life
      threatening ventricular arrhythmias. The patient was subsequently found to have
      acute occlusion of the proximal right coronary artery (RCA) and proximal left
      anterior descending coronary artery (LAD). The patient was treated with primary
      percutaneous coronary interventions for RCA and LAD, and intra-aortic balloon
      pump placement showed excellent results. Based on the available literature, early
      PCI for this very rare condition is paramount for patient survival.

PMID- 22388314
TI  - Recurrent cardiac tamponade following unusual micro leak after successful closure
      of the primary leak.
AB  - Although uncommon, coronary artery perforation is one of the most dreadful
      complications of percutaneous coronary intervention, which requires prompt,
      aggressive, and effective management. Perforations induced by coronary guidewires
      are usually located in the distal part of a coronary artery and commonly managed
      with embolization. This is an unusual case report of guidewire-induced coronary
      perforation with recurrent cardiac tamponade, which was managed successfully by
      coil embolization of both ipsilateral and contralateral coronary arteries via
      transradial approach.

PMID- 22388315
TI  - Successful treatment of SVC syndrome using isolated pharmacomechanical
      thrombolysis.
AB  - We report 2 cases of superior vena cava (SVC) syndrome treated using isolated
      pharmacomechanical thrombolysis with angioplasty alone. We also propose a new
      staged treatment strategy to optimally manage such patients, taking into
      consideration both cost-effectiveness and the ultimate prognosis.

PMID- 22388316
TI  - Percutaneous treatment of Lutembacher syndrome in a case with difficult mitral
      valve crossing.
AB  - Most cases of combination congenital cardiac anomalies are treated with open
      heart surgeries because the coexisting anomalies change the cardiac anatomy in an
      adverse way, making catheter manipulations complex. Lutembacher syndrome is a
      combination of acquired mitral stenosis and congenital ostium secundum atrial
      septal defect. The large defect in the septum makes an Inoue balloon catheter
      unstable, which provides excessive space for free floatation of the catheter,
      making its passage into the left ventricle difficult by Inoue technique. We
      present a case of elective definitive percutaneous treatment of Lutembacher
      syndrome, discussing the technical difficulties faced in mitral valve crossing
      and reviewing the possible strategies to improve chances of success.

PMID- 22388317
TI  - Distal open sesame and hairpin wire techniques to facilitate a chronic total
      occlusion intervention.
AB  - We describe a novel distal "open sesame" and "hairpin wire" technique application
      in a right coronary artery (RCA) chronic total occlusion intervention. Antegrade
      wiring was successful in entering an acute marginal branch distal to the
      occlusion, but not the mid RCA. After predilation, antegrade flow was restored
      but the mid RCA could not be wired in spite of using multiple different
      guidewires. A "hairpin" was created in a polymer jacketed guidewire, advanced
      into the acute marginal branch, and withdrawn, allowing wiring of the mid RCA,
      which was successfully stented using a variety of guide support and lesion
      preparation techniques.

PMID- 22388318
TI  - Embolization of immediate release transcatheter patch for atrial septal defect
      occlusion: the causes and the pitfalls to avoid.
AB  - We report embolization of a bioabsorbable immediate-release patch for closure of
      atrial septal defect into left atrium with forward movement into and out of the
      mitral valve during each cardiac cycle. The dislodged device was ultimately
      explanted by a surgical operation and the defect was closed. We discuss causes
      and recommend tips to prevent such a serious potential complication. We also
      suggest some modifications to the device for making it more safe and effective.

PMID- 22388319
TI  - The polyphenols resveratrol and S17834 prevent the structural and functional
      sequelae of diet-induced metabolic heart disease in mice.
AB  - BACKGROUND: Diet-induced obesity is associated with metabolic heart disease
      characterized by left ventricular hypertrophy and diastolic dysfunction.
      Polyphenols such as resveratrol and the synthetic flavonoid derivative S17834
      exert beneficial systemic and cardiovascular effects in a variety of settings
      including diabetes mellitus and chronic hemodynamic overload. METHODS AND
      RESULTS: We characterized the structural and functional features of a mouse model
      of diet-induced metabolic syndrome and used the model to test the hypothesis that
      the polyphenols prevent myocardial hypertrophy and diastolic dysfunction. Male
      C57BL/6J mice were fed a normal diet or a diet high in fat and sugar (HFHS) with
      or without concomitant treatment with S17834 or resveratrol for up to 8 months.
      HFHS diet-fed mice developed progressive left ventricular hypertrophy and
      diastolic dysfunction with preservation of systolic function in association with
      myocyte hypertrophy and interstitial fibrosis. In HFHS diet-fed mice, there was
      increased myocardial oxidative stress with evidence of oxidant-mediated protein
      modification via tyrosine nitration and 4-OH-2-nonenol adduction. HFHS diet-fed
      mice also exhibited increases in plasma fasting glucose, insulin, and homeostasis
      model assessment of insulin resistance indicative of insulin resistance.
      Treatment with S17834 or resveratrol prevented left ventricular hypertrophy and
      diastolic dysfunction. For S17834, these beneficial effects were associated with
      decreases in oxidant-mediated protein modifications and hyperinsulinemia and
      increased plasma adiponectin. CONCLUSIONS: Resveratrol and S17834 administered
      concurrently with a HFHS diet prevent the development of left ventricular
      hypertrophy, interstitial fibrosis, and diastolic dysfunction. Multiple
      mechanisms may contribute to the beneficial effects of the polyphenols, including
      a reduction in myocardial oxidative stress and related protein modifications,
      amelioration of insulin resistance, and increased plasma adiponectin. The
      polyphenols resveratrol and S17834 may be of value in the prevention of diet
      induced metabolic heart disease.

PMID- 22388320
TI  - Developmental endothelial locus-1 (Del-1) mediates clearance of platelet
      microparticles by the endothelium.
AB  - BACKGROUND: Phosphatidylserine-expressing microparticles circulate in blood with
      a short half-life of <10 minutes. We tested the role of an endothelium-derived
      phosphatidylserine-binding opsonin, developmental endothelial locus-1 (Del-1), in
      the uptake of platelet microparticles. METHODS AND RESULTS: Cultured human
      umbilical vein and microvascular endothelial cells avidly engulf BODIPY (4,4
      difluoro-4-bora-3a,4a-diaza-s-indacene)-maleimide-labeled platelet
      microparticles. Microparticle uptake was inhibited by a monoclonal antibody to
      Del-1 (P=0.027) and by annexin A5 (P=0.027), abciximab (P=0.027), a monoclonal
      antibody to integrin alphaVbeta3 (P=0.027), and chlorpromazine (P=0.027). These
      results suggest that Del-1 mediates phosphatidylserine- and integrin-dependent
      endothelial uptake of microparticles by endocytosis. To assess the in vivo
      significance, we infused fluorescent platelet microparticles into the inferior
      vena cava of mice and harvested endothelial cells from the pulmonary and systemic
      circulation. Compared with their wild-type littermates, Del-1-deficient mice had
      decreased uptake in endothelial cells in lung (3.07+/-1.9 versus 1.09+/-1.3,
      P=0.02) and liver (2.85+/-1.1 versus 1.35+/-0.92, P=0.01). Furthermore, after
      endotoxin administration, Del-1-deficient mice displayed an increase in the level
      of microparticles compared with wild-type mice (P=0.02). CONCLUSIONS: These
      studies show a physiological role for Del-1 in the clearance of
      phosphatidylserine-expressing microparticles by endothelium.

PMID- 22388321
TI  - Del-etion of microvesicles from the circulation.

PMID- 22388322
TI  - Immune cell modulation of cardiac remodeling.

PMID- 22388323
TI  - Activation of CD4+ T lymphocytes improves wound healing and survival after
      experimental myocardial infarction in mice.
AB  - BACKGROUND: The role of adaptive immunity, especially CD4(+) T-helper cells, has
      not yet been systematically investigated in wound healing and remodeling after
      myocardial infarction (MI). Therefore, we studied whether CD4(+) T cells become
      activated and influence wound healing after experimental MI in mice. METHODS AND
      RESULTS: When we compared sham versus MI in wild-type (WT) mice, T-cell receptor
      dependent activation of both conventional Foxp3(-) and regulatory Foxp3(+) CD4(+)
      T cells could be demonstrated in heart-draining lymph nodes within the first week
      after MI. Concomitantly, we found infiltration of CD4(+) T cells in infarcted
      myocardium. To study the role of CD4(+) T cells in wound healing and remodeling,
      CD4(+) T-cell-deficient mice (CD4 knockout [KO], MHCII(Delta/Delta)) and T-cell
      receptor-transgenic OT-II mice recognizing an irrelevant ovalbumin-derived
      peptide were studied. Serial echocardiography up to day 56 after MI revealed
      increased left ventricular dilation in CD4 KO compared with WT mice. Within the
      infarcted myocardium, CD4 KO mice displayed higher total numbers of leukocytes
      and proinflammatory monocytes (18.3+/-3.0 10(4)/mg WT versus 75.7+/-17.0 10(4)/mg
      CD4 KO, P<0.05). MHCII(Delta/Delta) and OT-II mice displayed significantly
      greater mortality (21% WT versus 48% OT-II, P<0.05, and WT 22% versus 52%
      MHCII(Delta/Delta), P<0.05) and myocardial rupture rates than WT mice. Collagen
      matrix formation in the infarct zone was severely disturbed in CD4 KO and
      MHCII(Delta/Delta) mice, as well as in OT-II mice. CONCLUSIONS: The present study
      provides the first evidence that CD4(+) T cells become activated after MI,
      presumably driven by recognition of cardiac autoantigens, and facilitate wound
      healing of the myocardium.

PMID- 22388324
TI  - Auto-antigenic protein-DNA complexes stimulate plasmacytoid dendritic cells to
      promote atherosclerosis.
AB  - BACKGROUND: Inflammation has been closely linked to auto-immunogenic processes in
      atherosclerosis. Plasmacytoid dendritic cells (pDCs) are specialized to produce
      type-I interferons in response to pathogenic single-stranded nucleic acids, but
      can also sense self-DNA released from dying cells or in neutrophil extracellular
      traps complexed to the antimicrobial peptide Cramp/LL37 in autoimmune disease.
      However, the exact role of pDCs in atherosclerosis remains elusive. METHODS AND
      RESULTS: Here we demonstrate that pDCs can be detected in murine and human
      atherosclerotic lesions. Exposure to oxidatively modified low-density lipoprotein
      enhanced the capacity of pDCs to phagocytose and prime antigen-specific T cell
      responses. Plasmacytoid DCs can be stimulated to produce interferon-alpha by
      Cramp/DNA complexes, and we further identified increased expression of Cramp and
      formation of neutrophil extracellular traps in atherosclerotic arteries. Whereas
      Cramp/DNA complexes aggravated atherosclerotic lesion formation in apolipoprotein
      E-deficient mice, pDC depletion and Cramp-deficiency in bone marrow reduced
      atherosclerosis and anti-double-stranded DNA antibody titers. Moreover, the
      specific activation of pDCs and interferon-alpha treatment promoted plaque
      growth, associated with enhanced anti-double-stranded-DNA antibody titers.
      Accordingly, anti-double-stranded DNA antibodies were elevated in patients with
      symptomatic versus asymptomatic carotid artery stenosis. CONCLUSIONS: Self-DNA
      (eg, released from dying cells or in neutrophil extracellular traps) and an
      increased expression of the antimicrobial peptide Cramp/LL37 in atherosclerotic
      lesions may thus stimulate a pDC-driven pathway of autoimmune activation and the
      generation of anti-double-stranded-DNA antibodies, critically aggravating
      atherosclerosis lesion formation. These key factors may thus represent novel
      therapeutic targets.

PMID- 22388326
TI  - National Heart, Lung, and Blood Institute Workshop: improving outcomes for
      pulmonary vascular disease.

PMID- 22388325
TI  - Mitral valve prolapse with mid-late systolic mitral regurgitation: pitfalls of
      evaluation and clinical outcome compared with holosystolic regurgitation.
AB  - BACKGROUND: Mitral regurgitation (MR) of mitral valve prolapse predominates in
      late systole but may be holosystolic or purely mid-late systolic, but the impact
      of MR timing on MR left ventricular and left atrial consequences and outcome is
      unknown. Whether effective regurgitant orifice (ERO) by the flow convergence
      method is similarly linked to outcome in mid-late systolic MR and holosystolic MR
      is uncertain. METHODS AND RESULTS: We comprehensively and prospectively
      quantified MR in 111 patients with mitral valve prolapse and mid-late systolic MR
      and matched them to 90 patients with mitral valve prolapse and holosystolic MR
      for age, gender, atrial fibrillation, ejection fraction, and ERO (flow
      convergence). Mid-late systolic MR versus holosystolic MR groups were well
      matched, including for comorbidity, blood pressure, and heart rate (all P>0.10).
      Mid-late systolic MR versus holosystolic MR caused similar color jet area,
      midsystolic regurgitant flow, and peak velocity (P>0.40). Despite identical ERO
      (0.25+/-0.15 versus 0.25+/-0.15 cm(2); P=0.53), the shorter duration of mid-late
      systolic MR (233+/-56 versus 426+/-50 ms; P<0.0001) yielded lower regurgitant
      volume (24.8+/-13.4 versus 48.6+/-25.6 mL; P<0.0001). MR consequences, systolic
      pulmonary pressure, and left ventricular and left atrial volume index (all
      P<0.001) were more benign in mid-late systolic MR versus holosystolic MR. Under
      medical management, fewer cardiac events (5 years: 15.8+/-4.6% versus 40.4+/
      6.1%; P<0.0001) occurred in mid-late systolic MR versus holosystolic MR,
      requiring less mitral surgery. Multivariable analysis confirmed the independent
      association of mid-late systolic MR with benign consequences and outcomes (all
      P<0.01). Absolute ERO was not linked to outcome, in contrast to regurgitant
      volume. CONCLUSIONS: MR of mitral valve prolapse that is purely mid-late systolic
      causes more benign consequences and outcomes than holosystolic MR. Assessment may
      be misleading because jet area and ERO by flow convergence appear similar to
      those of holosystolic MR. However, shorter MR yields lower regurgitant volume,
      consequences, and benign outcomes. Instantaneous ERO by flow convergence should
      be interpreted in context, and in mid-late systolic MR, regurgitant volume
      provides information more reflective of MR severity. Therefore, for clinical
      management and surgical referral, clinicians should carefully take into account
      the timing and consequences of MR.

PMID- 22388328
TI  - Intravenous neostigmine for postoperative acute colonic pseudo-obstruction.
AB  - OBJECTIVE: To review the literature on the safety and effectiveness of
      neostigmine for the treatment of postoperative acute colonic pseudo-obstruction.
      DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases from November
      1969 to November 2011 were queried for articles published in English, using the
      search terms neostigmine, acute colonic pseudo-obstruction, postoperative,
      surgery, and Ogilvie syndrome. STUDY SELECTION AND DATA EXTRACTION: All relevant
      original studies, meta-analyses, systematic reviews, guidelines, and review
      articles were assessed for inclusion. References from pertinent articles were
      examined for additional content not found during the initial search. DATA
      SYNTHESIS: Neostigmine may provide an effective treatment option for
      postoperative acute colonic pseudo-obstruction (ACPO) after conservative
      treatment measures have failed. One randomized controlled trial, 8 prospective
      and 3 retrospective observational studies, and 9 case reports evaluated
      neostigmine for ACPO. Included studies were limited by small sample sizes and
      heterogeneous populations not focused on postoperative patients, use of adjuvant
      agents, and lack of a consistent neostigmine regimen. CONCLUSIONS: Neostigmine
      may be a safe and effective treatment option for postoperative ACPO; however,
      current data do not support its use as a first-line intervention. Prospective and
      retrospective studies have demonstrated improvement in clinical symptoms,
      reduction in time to resolution, and reduction of recurrence for patients who
      failed conservative management. Prospective clinical trial data that evaluate
      early neostigmine versus conservative management are critically needed to
      determine neostigmine's role as a first-line therapy for ACPO.

PMID- 22388329
TI  - Local cutaneous necrosis secondary to a prolonged peripheral infusion of
      methylene blue in vasodilatory shock.
AB  - OBJECTIVE: To report a case of methylene blue extravasation and subsequent tissue
      necrosis in a patient with refractory septic shock. CASE SUMMARY: A 47-year-old
      female presented with febrile neutropenia secondary to chemotherapy. The patient
      quickly decompensated to refractory septic shock in the critical care unit
      despite implementation of early goal-directed therapy as well as intravenous
      norepinephrine and vasopressin to stabilize her hemodynamic status. She received
      a 16-hour infusion of 1% methylene blue 0.25 mg*kg(-1)*h(-1), titrated up to 0.5
      mg*kg(-1)*h(-1), via a peripheral intravenous catheter. Ten hours after the start
      of the methylene blue infusion, she experienced a local extravasation injury,
      which led to distal digital necrosis. While her hemodynamic status improved
      dramatically, allowing discharge from the intensive care unit and eventually to
      home, the extravasation site became necrotic and required debridement and skin
      graft. DISCUSSION: Methylene blue is a vasoactive chemical that has been shown to
      provide hemodynamic stability in the treatment of refractory septic shock.
      Methylene blue administration is not considered standard of practice in the
      treatment of refractory septic shock and many aspects of its dosing, route,
      duration, and adverse effects are poorly described. As such, there is little
      guidance for its administration. We postulate that, in our patient, in the
      presence of systemic vasopressin and norepinephrine, methylene blue caused
      extensive vasoconstriction at the site of extravasation, resulting in tissue
      ischemia and necrosis. Tissue necrosis secondary to peripheral intravenous
      extravasation has not been previously described and is not listed as an adverse
      outcome on the drug monograph. The Naranjo probability scale indicates that the
      tissue necrosis was probably caused by the methylene blue extravasation.
      CONCLUSIONS: To mitigate future risk to limb and skin, we recommend that
      methylene blue infusions be delivered via central venous catheter. Extra care
      should be given to patients with risk factors for extravasation, such as
      sedation, presence of systemic disease, proximal intravenous puncture sites, and
      improperly placed catheters.

PMID- 22388330
TI  - Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic
      implications.
AB  - OBJECTIVE: To examine the relationship between polycystic ovary syndrome (PCOS),
      cardiovascular risk factors, cardiovascular disease (CVD), and chronic
      inflammation and analyze data regarding pharmacologic therapies that are
      recommended to reduce CVD risk in PCOS and the impact of those therapies on
      chronic inflammation. DATA SOURCES: A search of MEDLINE (1950-October 2011) was
      conducted to identify clinical studies pertaining to the identification and
      treatment of CVD and chronic low-grade inflammation in PCOS. Search terms
      included polycystic ovary syndrome, cardiovascular disease, inflammation,
      metformin, thiazolidinedione, and statin. Bibliographies of these studies and
      review articles were also examined. STUDY SELECTION AND DATA EXTRACTION: English
      language clinical studies evaluating the effect of metformin, thiazolidinediones,
      and statins on inflammatory markers, endothelial function, adhesion molecules,
      fibrinolysis, cytokines, and adipokines in PCOS were included. DATA SYNTHESIS:
      Women with PCOS have an increased prevalence of many cardiovascular risk factors
      including obesity, android fat distribution, insulin resistance, impaired glucose
      tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Markers
      of chronic low-grade inflammation, which are associated with an increased risk of
      CVD, are also elevated in PCOS. Clinical guidelines recommend the use of insulin
      sensitizers and statins to prevent CVD in some patients with PCOS. Current
      literature indicates that each of these medication classes has beneficial effects
      on inflammation, as well. Although there are currently no studies to determine
      whether these treatments decrease CVD in PCOS, it can be hypothesized that drugs
      impacting chronic inflammation may reduce cardiovascular risk. Some studies show
      that metformin, thiazolidinediones, and statins have beneficial effects on
      inflammatory markers in PCOS; however, the data are inconsistent. CONCLUSIONS:
      There is insufficient information to recommend any pharmacologic therapies for
      their antiinflammatory effects in PCOS in the absence of other indications such
      as diabetes and dyslipidemia.

PMID- 22388331
TI  - Synthetic cathinones (bath salts): legal status and patterns of abuse.
AB  - OBJECTIVE: To review the current legal status and patterns of abuse of bath
      salts. DATA SOURCES: A literature search was conducted through MEDLINE (1950
      December 2011), PubMed (1966-December 2011), EMBASE (1966-December 2011), and
      International Pharmaceutical Abstracts (1970-December 2011) using the search
      terms bath salts, mephedrone, and methylenedioxypyrovalerone to identify articles
      on the legal status of bath salts and on studies focusing on patterns of abuse of
      bath salts. The GovTrack.us Web site was searched to determine the status of
      federal bills regarding bath salts. The National Association of Boards of
      Pharmacy and Drug Enforcement Administration Web sites and the Federal Register
      were also examined to identify legislation on bath salts. STUDY SELECTION AND
      DATA EXTRACTION: Case reports and studies regarding bath salts were examined.
      Federal laws involving bath salts were also evaluated. DATA SYNTHESIS: The
      Department of Justice issued a final order in the Federal Register, temporarily
      placing the 3 synthetic stimulants, mephedrone, methylenedioxypyrovalerone, and
      methylone, under Schedule I of the Controlled Substances Act. Literature
      evaluated included case reports, retrospective studies, surveys, toxicology data,
      and chemical analyses studies. Information in the literature demonstrated that
      bath salts are highly abused, and common adverse effects include hypertension,
      tachycardia, and psychiatric symptoms. CONCLUSIONS: Psychoactive substances
      recently sold as bath salts have been placed in Schedule I of the Controlled
      Substances Act. Pharmacists can play an important role in raising awareness on
      the dangers of bath salts abuse through patient counseling and community outreach
      programs. The evidence on legal status and patterns of abuse clearly demonstrates
      that bath salts contain dangerous substances that should be permanently
      controlled.

PMID- 22388332
TI  - Revealing the conversion mechanism of CuO nanowires during lithiation
      delithiation by in situ transmission electron microscopy.
AB  - Being promising candidates for anodes in lithium-ion batteries (LIBs), transition
      metal oxide anodes utilizing the so-called conversion mechanism principle
      typically suffer from the severe capacity fading during the 1st cycle of
      lithiation-delithiation. Herein, we directly investigated these processes using
      an individual CuO nanowire anode and constructed a lithium ion battery (LIB)
      prototype within a transmission electron microscope.

PMID- 22388333
TI  - Letter from the Editor-in-Chief.

PMID- 22388334
TI  - Manipulation efficacy: Upper body.
AB  - Manipulation, or manual medicine, is a highly utilized form of treatment for many
      types of musculoskeletal disorders, but there are many questions about the
      efficacy and safety of this form of treatment. This review of published trials
      for treatment of the upper body (cervical, thoracic, and upper limb) describes
      the patient groups that have been studied and may benefit from manual treatment,
      their outcomes, and their limitations. Cervical manipulation in particular has
      historically received criticism regarding safety, and the incidence of side
      effects, severe complications, and contraindications are discussed. The number of
      studies published for the upper body is small compared to the lumbar spine, and
      the lack of uniformity of the information still leaves the individual
      practitioner to decide if and when manipulation fits into his or her treatment
      algorithms for this region of the body.

PMID- 22388335
TI  - Magnetic and electromagnetic field therapy.
AB  - There is increasing interest in the application of magnetic/electromagnetic
      fields for therapeutic purposes. Magnetotherapy provides non-invasive, safe and
      easy to apply methods to directly treat the site of injury, the source of pain
      and inflammation as well as other types of dysfunction. This review summarizes
      several decades of experience worldwide in studying biological and clinical
      effects initiated by various magnetic and electromagnetic fields. The
      physiological basis for tissue repair as well as physical principles of dosimetry
      and application of magnetic fields are discussed. An analysis of
      magnetic/electromagnetic stimulation is followed by a discussion of the advantage
      of magnetic field stimulation compared with electric current stimulation.
      Finally, the proposed mechanisms of action are discussed.

PMID- 22388336
TI  - Lower beta-endorphin content of peripheral blood mononuclear cells in patients
      with complex regional pain syndrome.
AB  - Recent studies have demonstrated that immune cell-derived beta-endorphin inhibits
      peripheral nociception. Changes in the beta-endorphin content of peripheral blood
      mononuclear cells (PBMC) were also reported in various human disorders. These
      findings suggest the modulation of pain by immuno-neural interaction through
      opioid-dependent mechanisms. The aim of this study, therefore, was to determine
      whether the levels of beta-endorphin in PBMC of patients with complex regional
      pain syndrome (CRPS) differ from those of healthy subjects. Heparinized venous
      blood was collected from ten CRPS patients (7 women and 3 men; mean age 39.4 +/-
      13.0 years) and 13 age-matched healthy volunteers (6 women and 7 men; mean age
      38.4 +/- 10.8 years). PBMC were separated by density gradient centrifugation.
      beta- endorphin was extracted from the cells in a commercial cell lysis buffer
      and its concentration was measured by enzyme immunoassay technique.
      Immunoreactive beta-endorphin levels in PBMC from the CRPS patients were
      significantly lower than those from the healthy volunteers (101.5 +/- 57.5 versus
      222.1 +/- 77.6, P < 0.001), and were not correlated to the present pain intensity
      or pain duration. The results indicate an altered condition of the immune-linked
      opioid system underlying CRPS. Further immunological approaches may provide new
      insight into the pathophysiology of CRPS.

PMID- 22388337
TI  - The relationship of clinical and laboratory measurements to two different
      radiological scoring methods in ankylosing spondylitis.
AB  - Two different methods for scoring the severity of radiological changes in 19
      patients with ankylosing spondylitis, using plain X-rays of the lumbar spine and
      sacroiliac (SI) joints, were assessed in relation to clinical and laboratory
      measurements. Bath Ankylosing Spondylitis Radiology Index (BASRI) and Stoke
      Ankylosing Spondylitis Spine Score (SASSS) were used to evaluate radiologic
      changes. Disease activity was assessed using Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI). There was no correlation between duration of morning
      stiffness, night pain, laboratory variables (ESR, CRP, hemoglobin, platelets) and
      any of the radiological scores. No significant correlation was found between
      BASDAI and both of the radiological scores. BASRI and SASSS correlated
      significantly with occiput-to-wall distance, Schober test, and finger-to-fibula
      distance. There was no significant correlation of radiologic scores with finger
      to-floor distance and chest expansion. Right and left SI joint scores correlated
      significantly with BASRI and SASSS. The good correlation between spinal indexes
      and lack of correlation between clinical indicators of disease activity supports
      the notion that these two radiological scoring methods are measures of disease
      severity or deformity rather than disease activity. Radiological scoring methods
      are fundamental for the diagnosis and progression in AS and BASRI may be a more
      practical and appropriate method.

PMID- 22388338
TI  - The effects of a physiotherapeutic programme on bone mineral density, in
      individuals of postpuberty age (18--30 years), with cerebral palsy.
AB  - Celebral palsy (CP), unlike many other neurodevelopmental disorders, is
      associated with abnormalities of pregnancy and birth, particularly "birth
      asphyxia" and low birthweight. The aim of this research was to define and
      evaluate the degree up to which the physiotherapeutic treatment after puberty,
      when the musculoskeletal system is almost developed, can have a positive
      influence on bone mineral density (BMD). In the research 26 individuals having
      different forms of CP, 13 males and 13 females, participated. The percentage
      according to the form of the disease gender was tetraplegic 50% women, average
      age 25.4 years, diplegic 26.9% and 6 women, average age 27.2 years, hemiplegic
      23.1% individuals), 3 men and 3 women, average age 27.2 years. Before the
      measurements there were clinical tests and EEG's. The program was conducted 3
      times per week for twenty six (26) weeks and included energetic, energopathetic
      and energetic with resistance exercises. Each session consisted of a one-on-one
      program of exercise with the upper, lower extremities and lumbar region. Dual
      energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD)
      of the lumbar spine and femoral neck. To minimize operator-related variability,
      all scans were performed and analyzed by the same trained technologist. For the
      control of the statistical importance of the value changes the ANOVA test was
      used from the statistical package SPSS. After intervention, the physiotherapy
      group had a significantly greater increase in bone mineral density in femoral
      neck, compared with control subjects, but not in the lumbar region (L2-L4), where
      the physiotherapy program was not intense. The results of this investigation show
      that a 6-month physiotherapeutic program enhances bone mineral density in
      individuals with cerebral palsy. This supports the concept that a minimal period
      of exercise is successful in eliciting an osteogenic response in these groups.
      The therapeutic goal of physiotherapists and orthopaedics is to promote exercise,
      especially weight-bearing activity, to decrease fragility and susceptibility to
      fractures in patients with decreased activity.

PMID- 22388341
TI  - An epidemic of traumatic brain injury in professional cycling:  a call to action.

PMID- 22388339
TI  - Tendon vibration during submaximal isometric strength and postural tasks.
AB  - To establish the effect of tendon vibration (TV) on steady submaximal strength
      and static balance control, 29 women performed isometric plantarflexions at 10,
      20, 30 and 50% of MVC and postural tasks of increasing difficulty (Normal Quiet
      Stance, NQS, Sharpened Tandem Stance and One Leg Stance) with vibrators (80 Hz)
      applied to the Achilles tendon. Both tasks were performed under four conditions
      (10 s each): eyes open, eyes closed, eyes closed with TV, eyes open with TV.
      During the isometric tasks, the application of TV increased the plantarflexion
      torque at 20 and 30% of MVC, accompanied by a greater (p < 0.001) activation of
      agonists (Medial Gastrocnemius, MGAS and Soleus, SOL), as well as a greater (p <
      0.05) coactivation of the antagonist (tibialis anterior, TA). Non-significant
      differences were observed at 10 and 50% of MVC. During posture, TV resulted in a
      backward displacement of the Centre of Pressure only for NQS and an increase (p <
      0.01) in EMG activity of the ankle muscles in all balance tasks. The MGAS
      contraction during TV application was confirmed (by ultrasonography) at ten
      participants by an increase of the pennation angle and decrease of its fascicle
      length (p < 0.05). The vibration-induced muscle excitation and accompanying
      increase in motor output, probably due to excitatory Ia afferent input, was
      confirmed during strength and postural tasks. However, motor output attenuates
      when the magnitude of central drive to the ankle muscles increases.

PMID- 22388342
TI  - A proposed method to reduce underreporting of brain injury in sports.

PMID- 22388343
TI  - The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with
      asthma and nonasthmatic subjects.
AB  - OBJECTIVE: Data on pharmacokinetics of inhaled and oral salbutamol in elite
      athletes with asthma are needed to differentiate between therapeutic use and
      doping in doping control. DESIGN: An interventional open-label crossover.
      SETTING: Respiratory Research Unit, Copenhagen University Hospital, Bispebjerg.
      PARTICIPANTS: Eight elite athletes with asthma and 10 nonasthmatic subjects aged
      18 to 33 years. INTERVENTION: Administration of 0.8 mg of inhaled salbutamol and
      8 mg of oral salbutamol separated by 14 days. MAIN OUTCOME MEASURES: Urine
      concentration of free salbutamol. RESULTS: Maximum urine concentrations peaked in
      the period of 0 to 4 hours after the administration of inhaled and oral
      salbutamol in both groups. Median concentrations after inhaled salbutamol and
      oral salbutamol were 401.6 and 2108.1 ng/mL in healthy subjects and 334.9 and
      2975.2 ng/mL in elite athletes with asthma. There were no significant statistical
      differences between the groups. One sample exceeded the World Anti-Doping Agency
      threshold value of 1000 ng/mL with a urinary salbutamol concentration of 1057
      ng/mL 4 hours after inhalation, when no correction for urine specific gravity was
      done. When this sample was corrected for urine specific gravity, the result was
      661 ng/mL. CONCLUSIONS: We found no significant difference in pharmacokinetic
      profile of inhaled and oral salbutamol between elite athletes with asthma and
      nonasthmatic subjects. Our results indicate that urine salbutamol concentrations
      should be corrected for urine specific gravity when evaluating doping cases.

PMID- 22388344
TI  - Time spent sitting and idiopathic pulmonary embolism in women.

PMID- 22388345
TI  - The effectiveness of nonoperative treatment for frozen shoulder:  a systematic
      review.

PMID- 22388346
TI  - Surgical versus nonsurgical treatment of acute Achilles tendon rupture.

PMID- 22388347
TI  - Shockwave therapy for chronic proximal hamstring tendinopathy.

PMID- 22388349
TI  - Inhibition of Drp1 provides neuroprotection in vitro and in vivo.
AB  - Impaired regulation of mitochondrial dynamics, which shifts the balance towards
      fission, is associated with neuronal death in age-related neurodegenerative
      diseases, such as Alzheimer's disease or Parkinson's disease. A role for
      mitochondrial dynamics in acute brain injury, however, has not been elucidated to
      date. Here, we investigated the role of dynamin-related protein 1 (Drp1), one of
      the key regulators of mitochondrial fission, in neuronal cell death induced by
      glutamate toxicity or oxygen-glucose deprivation (OGD) in vitro, and after
      ischemic brain damage in vivo. Drp1 siRNA and small molecule inhibitors of Drp1
      prevented mitochondrial fission, loss of mitochondrial membrane potential (MMP),
      and cell death induced by glutamate or tBid overexpression in immortalized
      hippocampal HT-22 neuronal cells. Further, Drp1 inhibitors protected primary
      neurons against glutamate excitotoxicity and OGD, and reduced the infarct volume
      in a mouse model of transient focal ischemia. Our data indicate that Drp1
      translocation and associated mitochondrial fission are key features preceding the
      loss of MMP and neuronal cell death. Thus, inhibition of Drp1 is proposed as an
      efficient strategy of neuroprotection against glutamate toxicity and OGD in vitro
      and ischemic brain damage in vivo.

PMID- 22388350
TI  - Mdm2 controls CREB-dependent transactivation and initiation of adipocyte
      differentiation.
AB  - The role of the E3 ubiquitin ligase murine double minute 2 (Mdm2) in regulating
      the stability of the p53 tumor suppressor is well documented. By contrast,
      relatively little is known about p53-independent activities of Mdm2 and the role
      of Mdm2 in cellular differentiation. Here we report a novel role for Mdm2 in the
      initiation of adipocyte differentiation that is independent of its ability to
      regulate p53. We show that Mdm2 is required for cAMP-mediated induction of
      CCAAT/enhancer-binding protein delta (C/EBPdelta) expression by facilitating
      recruitment of the cAMP regulatory element-binding protein (CREB) coactivator,
      CREB-regulated transcription coactivator (Crtc2)/TORC2, to the c/ebpdelta
      promoter. Our findings reveal an unexpected role for Mdm2 in the regulation of
      CREB-dependent transactivation during the initiation of adipogenesis. As Mdm2 is
      able to promote adipogenesis in the myoblast cell line C2C12, it is conceivable
      that Mdm2 acts as a switch in cell fate determination.

PMID- 22388351
TI  - Reduced expression of BTBD10, an Akt activator, leads to motor neuron death.
AB  - BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A
      mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10
      suppresses motor neuron death that is induced by a familial amyotrophic lateral
      sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro.
      In this study, we further investigated the BTBD10-mediated suppression of motor
      neuron death. We found that the small interfering RNA-mediated inhibition of
      BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis
      elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of
      neurons, including both motor and touch-receptor neurons, but also a locomotion
      defect. In addition, we found that the expression of BTBD10 was generally
      decreased in the motor neurons from patients of sporadic ALS and transgenic mice
      overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results
      suggest that the reduced expression of BTBD10 leads to motor neuron death both in
      vitro and in vivo.

PMID- 22388352
TI  - Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation
      of the death accelerator Bik.
AB  - Src, the canonical member of the non-receptor family of tyrosine kinases, is
      deregulated in numerous cancers, including colon and breast cancers. In addition
      to its effects on cell proliferation and motility, Src is often considered as an
      inhibitor of apoptosis, although this remains controversial. Thus, whether the
      ability of Src to generate malignancies relies on an intrinsic aptitude to
      inhibit apoptosis or requires preexistent resistance to apoptosis remains
      somewhat elusive. Here, using mouse fibroblasts transformed with v-Src as a
      model, we show that the observed Src-dependent resistance to cell death relies on
      Src ability to inhibit the mitochondrial pathway of apoptosis by specifically
      increasing the degradation rate of the BH3-only protein Bik. This effect relies
      on the activation of the Ras-Raf-Mek1/2-Erk1/2 pathway, and on the
      phosphorylation of Bik on Thr124, driving Bik ubiquitylation on Lys33 and
      subsequent degradation by the proteasome. Importantly, in a set of human cancer
      cells with Src-, Kras- or BRAF-dependent activation of Erk1/2, resistances to
      staurosporine or thapsigargin were also shown to depend on Bik degradation rate
      via a similar mechanism. These results suggest that Bik could be a rate-limiting
      factor for apoptosis induction of tumor cells exhibiting deregulated Erk1/2
      signaling, which may provide new opportunities for cancer therapies.

PMID- 22388353
TI  - The Apaf-1-binding protein Aven is cleaved by Cathepsin D to unleash its anti
      apoptotic potential.
AB  - The anti-apoptotic molecule Aven was originally identified in a yeast two-hybrid
      screen for Bcl-x(L)-interacting proteins and has also been found to bind Apaf-1,
      thereby interfering with Apaf-1 self-association during apoptosome assembly. Aven
      is expressed in a wide variety of adult tissues and cell lines, and there is
      increasing evidence that its overexpression correlates with tumorigenesis,
      particularly in acute leukemias. The mechanism by which the anti-apoptotic
      activity of Aven is regulated remains poorly understood. Here we shed light on
      this issue by demonstrating that proteolytic removal of an inhibitory N-terminal
      Aven domain is necessary to activate the anti-apoptotic potential of the
      molecule. Furthermore, we identify Cathepsin D (CathD) as the protease
      responsible for Aven cleavage. On the basis of our results, we propose a model of
      Aven activation by which its N-terminal inhibitory domain is removed by CathD
      mediated proteolysis, thereby unleashing its cytoprotective function.

PMID- 22388356
TI  - Cell and molecular mechanisms of regeneration and reorganization of skeletal
      muscles.
AB  - The process of skeletal muscle regeneration comprises four phases: degeneration,
      inflammatory and immune response, regeneration and remodelling, which are
      regulated by a number of molecules secreted, by muscle cells and immune,
      epithelial, interstitial and other cells present in skeletal tissue. The
      molecules include cytokines, growth factors, erythropoietin, enzymes, and
      reactive oxygen and nitrogen species (RONS).  Some of them are potent stimulators
      of the proliferation and growth of muscle cells while others may inhibit these
      processes. For several years, cytokines and growth factors have been used in
      regenerative medicine in the form of platelet concentrate or recombinant
      preparations. There have also been attempts to use muscle cells and muscle
      derived stem cell (MDSC) cultures, which contain satellite glial cells,
      mesoanglioblasts and pericytes, as well as cultures of isolated satellite glial
      cells or myoblasts.  The aim of the paper is to present current knowledge
      concerning the molecular and cellular mechanisms of regeneration and remodelling
      of skeletal muscles, the role of cytokines and growth factors in the
      proliferation of satellite glial cells and the possibilities of therapeutic use
      of stem cells of different origin for stimulating regeneration of damaged muscle
      fibres.

PMID- 22388357
TI  - The use of kinesiology taping method in patients with rheumatoid hand--pilot
      study.
AB  - BACKGROUND: Rheumatoid arthritis (RA) most frequently affects smaller joints in
      the hands and feet. Among the most common deformations resulting from the
      progression of the disease are ulnar deviation, Boutonniere deformity, swan neck
      deformity, contractures and limited range of movement in the hand and wrist
      joints, muscular atrophy of long and short muscles. The topic of this article is
      the influence of using Kinesiology Taping method on the functioning of the hand
      of the patient suffering from rheumatoid arthritis. MATERIAL AND METHODS: The
      research involved 20 patients suffering from rheumatoid arthritis (16 women, 4
      men), treated in the Hospital in Kup. Average age of patients was 62.2. Research
      subjects, apart from pharmacological treatment in the hospital ward, received
      standard physiotherapy. In case of 10 patients additional K-Active Tape
      applications were used to correct ulnar positioning of the hand and improve hand
      functioning. Prior to physiotherapy, all patients were given a hand functioning
      test and a dynamometer measurement was made. The tests were repeated after the 2
      week rehabilitation process has been completed. The results were subjected to
      statistical analysis with the use of the Wilcoxon test and the U Mann-Whitney
      test. The assessment of the correlation between analysed parameters was made with
      the use of linear correlation test. RESULT: In the group where Kinesiology Tape
      applications were used, hand muscle strength increased significantly (p<0.05) in
      comparison with the group treated with standard physiotherapy. Hand muscle
      strength increase correlated with the tempo of carrying out the hand functioning
      test (r>0.8). CONCLUSION: Results suggest Kinesiology Taping method useful for
      physiotherapy of rheumatoid hand.

PMID- 22388354
TI  - Evolutionary genomics of Colias Phosphoglucose Isomerase (PGI) introns.
AB  - Little is known of intron sequences' variation in cases where eukaryotic gene
      coding regions undergo strong balancing selection. Phosphoglucose isomerase, PGI,
      of Colias butterflies offers such a case. Its 11 introns include many point
      mutations, insertions, and deletions. This variation changes with intron position
      and length, and may leave little evidence of homology within introns except for
      their first and last few basepairs. Intron position is conserved between PGIs of
      Colias and the silkmoth, but no intron sequence homology remains. % GC content
      and length are functional properties of introns which can affect whole-gene
      transcription; we find a relationship between these properties which may indicate
      selection on transcription speed. Intragenic recombination is active in these
      introns, as in coding sequences. The small extent of linkage disequilibrium (LD)
      in the introns decays over a few hundred basepairs. Subsequences of Colias
      introns match subsequences of other introns, untranslated regions of cDNAs, and
      insect-related transposons and pathogens, showing that a diverse pool of sequence
      fragments is the source of intron contents via turnover due to deletion,
      recombination, and transposition. Like Colias PGI's coding sequences, the introns
      evolve reticulately with little phylogenetic signal. Exceptions are coding-region
      allele clades defined by multiple amino acid variants in strong LD, whose introns
      are closely related but less so than their exons. Similarity of GC content
      between introns and flanking exons, lack of small introns despite mutational bias
      toward deletion, and findings already mentioned suggest constraining selection on
      introns, possibly balancing transcription performance against advantages of
      higher recombination rate conferred by intron length.

PMID- 22388358
TI  - Evaluation of blood loss and significance of postoperative autotransfusion   in
      knee joint alloplasty.
AB  - BACKGROUND: The aim of this paper is to evalute perioperative blood loss
      associated with total cemented knee joint alloplasty, with special regard to
      specific factors that may influence this loss. Additionally, the significance of
      postoperative autotransfusion in these procedures is assessed. MATERIALS AND
      METHODS: The study group consisted of 85 patients (61 females and 24 males); in
      32 cases a postoperative autotransfusion system was used (CBCII ConstaVac,
      Stryker). Factors analysed comprised pre- and postoperative hemoglobin levels,
      drain blood loss, heterologous blood transfusion volume and reasons for the
      transfusion, including co-morbidities. RESULTS: Allogeneic blood transfusion was
      necessary in 54.72% of the patients who did not have autotransfusion and in
      34.38% of the patients who received autotransfusion. The mean volume of blood
      collected in the drains was 882 ml, while the mean volume of reinfused blood
      amounted to 524.2 ml. Hypertensive patients experienced greater postoperative
      blood loss. The average drop in hemoglobin levels was 3.6 g/dl and was smaller by
      0.6 g/dl in patients who received autotransfusion. The lowest preoperative
      hemoglobin values occurred in patients who required heterologous blood
      transfusion despite autotransfusion. Heterologous blood transfusion was performed
      at a hemoglobin level of 8.4 g/dl; in patients with a concomitant ischemic heart
      disease the cut-off value was 9.6 g/dl. CONCLUSIONS: 1. The average drop in
      hemoglobin levels associated with knee alloplasty was 3.5 g/dl. The volume of
      recovered blood used for post-operative autotransfusion was approx. 500 ml. 2. A
      low preoperative hemoglobin level is the most significant risk factor for
      heterologous blood transfusion. 3. Co-mordibities need to be taken into
      consideration when determining the amount of blood required.

PMID- 22388359
TI  - Treatment for periprosthetic infection with two-stage revision arthroplasty with
      a gentamicin loaded spacer.  The clinical outcomes.
AB  - BACKGROUND: With the increasing number of total joint replacement procedures, the
      number of complications from that surgery has also been on the rise. Although
      quite rare (<1%), a PPI may ruin even the best and technically excellent joint
      replacement procedure, causing extensive damage and loss of bone and
      periprosthetic tissues, which makes subsequent restoration surgery extremely
      difficult. At present, a two-stage revision arthroplasty seems to be the best
      solution for PPI patients [4,9,15]. In the first stage, implant removal and
      radical debridement of infected tissues is performed and an antibiotic-loaded
      spacer is inserted. After a few months, the second stage is performed where the
      spacer is removed and a revision endoprosthesis is implanted. The aim of the
      study was to evaluate the effectiveness of treatment for periprosthetic
      infections with a two-stage revision arthroplasty. MATERIAL AND METHODS: Forty
      one patients diagnosed with PPI were treated at the Department of Orthopedic and
      Trauma Surgery, Silesian Medical University in Katowice, between January 2007 and
      March 2010. PPI was a complication of knee arthroplasty (12 patients, 29%) and
      hip replacement (29 patients, 71%). During the first stage of the treatment,
      intraoperative cultures were negative in 17 patients (41%) and positive in 24
      (59%). RESULTS: Cultures obtained in patients with reinfection after revision
      endoprosthesoplasty (second stage of the treatment) grew no pathogen in 1
      patient, MSSA (1), E. faecalis (1), and A. baumanii with MSSA and MRSE (1). After
      the first stage of the treatment (spacer implantation), infection was not cured
      in one patient (2.5%). In 4 patients (10%), there was reinfection after the
      implantation of a revision endoprosthesis. CONCLUSIONS: Our analysis provides
      evidence to suggest that two-stage revision endoprosthesoplasty is an effective
      method of treatment of periprosthetic infections.

PMID- 22388360
TI  - The Gibson and Piggott osteotomy for adult hallux valgus.
AB  - BACKGROUND: The Gibson and Piggott procedure for hallux valgus is based on sound
      surgical principles addressing the basic pathologies of this disorder. However,
      this procedure has not been studied extensively in the literature in comparison
      to the Mitchell and Chevron osteotomies. MATERIAL AND METHODS: We report a
      prospective study conducted on 50 adult feet with hallux valgus. The Gibson and
      Piggot osteotomy was done on all the feet. RESULTS: We obtained 76% excellent and
      18% good results with this procedure. CONCLUSION: The results bear out the fact
      that this procedure is a useful procedure for the management of this disorder.

PMID- 22388361
TI  - The relevance choice of  indexes to foot structure evaluation in the light of
      factors analysis.
AB  - BACKGROUND: An evaluation of the correctness in of feet structure is decisive
      significance with regard to the prevention and correction of their deformation.
      The aim of this work was an attempt to verify which of the indexes used in
      ascertaining longitudinal arch, transverse arch and foot proportions have the
      greater diagnostic force and therefore are the most accurate in premise. MATERIAL
      AND METHODS: Cross-sectional studies included 130 randomly selected students. The
      tested men were aged 20-28. A plantographic method non-marking technique was used
      to evaluate the feet. The indexes evaluating the longitudinal arch of the foot,
      the transverse arch of the foot and foot proportions were obtained from the
      plantograms. Verification of relevance choice of plantographic indexes to feet
      evaluation was made by factors analysis. RESULTS: The index of depth of the
      longitudinal arch of the foot (W(gwp)) achieved the maximum load factor values.
      The Wejsflog index (W(wp)) has achieved highest values of the factor loads than
      heel angle. The length and width index (W(d-sz)) has achieved highest values of
      the factor loads than the foot corpulence index (T(s)). CONCLUSIONS: 1. The most
      valid index in use for the evaluation of the longitudinal arch of the feet is the
      index of depth of the longitudinal arch of the foot (W(gwp)). For evaluation of
      the transverse arch the most useful is the W(wp) Wejsflog index, while to
      evaluate the proportions of feet the most accurate is the length and width index
      (W(d-sz)).

PMID- 22388362
TI  - Non-union of isolated displaced triquetral body fracture--a case report.
AB  - Triquetral fractures are the second most common carpal fractures. Triquetral body
      fractures are the less common type of triquetral fractures but they can be missed
      on plain radiographs and a non-union can be associated with considerable
      morbidity and reduction in functional activities. We report a unique case of
      displaced isolated triquetral body fracture that was initially missed on plain
      radiographs and resulted in non-union. The fracture non-union was diagnosed on
      magnetic resonance imaging and was treated successfully with open reduction and
      internal fixation using compression screws, without bone grafting, and early
      mobilisation of the wrist allowing a return to premorbid activity levels. To our
      knowledge, this has not been previously described in the literature. We advocate
      early clinical suspicion of triquetral fractures in patients with persistent
      ulnar-sided wrist pain following trauma, and early evaluation using computed
      tomography or magnetic resonance imaging.

PMID- 22388363
TI  - Percutaneous thermoablation of osteoid osteoma--a case study.
AB  - Osteoid osteoma has been traditionally treated by curettage and en bloc
      resection.  These methods are now being replaced by low-invasive techniques. We
      present the description of a percutaneous thermoablation of a femoral neck
      osteoid osteoma performed under CT guidance in a 22-year-old female patient.

PMID- 22388421
TI  - Diurnal resting in brown lemurs in a dry deciduous forest, northwestern
      Madagascar: implications for seasonal thermoregulation.
AB  - Decreased activity has been reported in both nocturnal and diurnal primates
      during the prolonged dry season in western Madagascar, and this has been
      interpreted as a reaction to the severe environment, with its food scarcity
      and/or thermal stress. Several day-active lemurs rest more as trees defoliate,
      although the reason for this is unclear. To understand the mechanism underpinning
      the diurnal resting of lemurs in seasonal deciduous forests, I observed common
      brown lemurs (Eulemur fulvus fulvus) for one year in Ankarafantsika National
      Park, northwestern Madagascar. In Ankarafantsika, despite high fruit availability
      during the dry season, brown lemurs are known to engage in diurnal resting. To
      examine the effects of thermal factors and defoliation on lemur inactivity, I
      recorded the activity of a troop at 1 min intervals, hourly ambient temperature,
      daily rainfall, and weather during observations (06:00-18:00). I quantified the
      amount of leaves biweekly for 680 trees. I tested correlations between
      percentages of resting time and each factor across hours during the day and
      across seasons. During the rainy season, resting time did not differ between
      sunny and cloudy days, and lemurs were active throughout the daytime. At the
      hourly level during the dry season, lemurs rested exclusively at midday,
      apparently at peak sunlight intensity rather than at peak ambient temperature. At
      seasonal level, percentages of total resting time from 08:00 to 16:00 were
      greater during dry season (81.9%) than during rainy season (62.6%), and
      percentages increased as ambient temperatures increased. Defoliation was related
      to seasonal decrease in weekly rainfall, which served as an index of water
      retained in the forest. Defoliation probably reflected aridification as well as
      the penetration of sunlight into the forest. Diurnal resting increased as both
      the amount of leaves and weekly rainfall decreased seasonally. These results
      suggest that heat stress under dry conditions may promote resting. Diurnal
      resting may function as behavioral thermoregulation to avoid overheating and to
      minimize water loss via excessive evaporative respiration.

PMID- 22388423
TI  - Measurements of absolute energy spectra for an industrial micro focal X-ray
      source under working conditions using a Compton scattering spectrometer.
AB  - Knowledge of absolute photon energy spectrum is essential for image quality
      analysis and optimisation for any X-ray imaging method, for example, radiography
      and computerised tomography (CT). Conventional quantities such as half-value
      layer (HVL) and effective energy are easily calculated from energy spectra. These
      quantities are, however, of limited value and use for image quality analysis. For
      example, two energy spectra with the same effective energy but different
      distributions will not yield the same signal in energy-dependent (read 'most')
      detectors. Accurate absolute energy spectra are, unfortunately, hard to
      generalise, since they depend on the specific X-ray source characteristic, that
      is, target material, internal filtration, high-tension generator, working load
      etc. They are also laborious to measure, which makes them hard to obtain.In this
      work absolute energy spectra [1/(keV mAs sr)] for an industrial micro focal X-ray
      source have been measured under working conditions, using a Compton scattering
      spectrometer. The energy spectra were measured as a function of tube potential
      (30-190 kV for every 10 kV) at maximum tube charge (8 W, i.e., tube potential *
      tube current) for the smallest focus diameter (~5 MUm). This is because the micro
      focal X-ray source in the application in mind is used mainly for high resolution
      CT, where its maximum fluence is required to shorten scanning times. Target
      material was tungsten. The spectra were measured for a highly focused fresh focal
      spot. Neither focal spot wear (age) nor defocusing of the focal spot was
      considered.The measured spectra were compared to simulated spectra for the same
      source supplied by the X-ray source manufacturer. It was found that the measured
      spectra have slightly different energy distributions with a lower mean energy
      even though their emitted numbers of photons were similar. The energy
      calibration, Deltahnu = 0.5 keV, was shown to be accurate compared to the energy
      resolution used.This work is a part of a larger project, where image quality
      dependence on X-ray equipment parameters has been studied. Even though the main
      interest has been in high resolution CT, much of the results and general
      discussions have wider applications. The full spectra data files are available on
      the Internet [5].

PMID- 22388422
TI  - Callithrix penicillata as a nonhuman primate model for strongyloidiasis.
AB  - In order to better understand experimental strongyloidiasis in small New World
      primates, and to evaluate aspects of reinfection and immunosuppression induced by
      glucocorticoids, nine specimens of Callithrix penicillata (Primates: Cebidae)
      were administered (by subcutaneous injection, sc) 3000 infective larvae of a
      strain of Strongyloides venezuelensis (Rhabditida: Strongyloididae) that had been
      maintained in successive passages through AKR/J mice since 1987. The mean
      prepatent period was 5.6 +/- 0.7 days post-infection (DPI). The mean patent
      period of infection among the untreated animals (marmosets 1-7) was 123.4 +/-
      61.4 DPI. Two animals (marmosets 8 and 9) received dexamethasone (2.5 mg/kg, sc)
      for five consecutive days starting on the 20th day after infection, but this
      treatment did not alter the course of the infection, and the patent period for
      these animals was 100.5 +/- 58.7 DPI (59 and 142, respectively). Stool
      examination showed that the highest quantities of parasite eggs were expelled
      between the 8th and 19th days after inoculation of the larvae. Thereafter, there
      was a gradual reduction in the number of parasite eggs in feces of all marmosets.
      During the chronic phase of the infection, before completely negative
      parasitological findings were obtained, the parasitological examinations were
      intermittently positive. Reinfection of three of these animals did not result in
      new positive examinations. However, given the receptiveness of these animals to
      initial infection with S. venezuelensis and their similarities to human beings,
      it is proposed that C. penicillata could be used as a nonhuman primate model for
      experimental strongyloidiasis.

PMID- 22388424
TI  - Image noise in X-ray imaging caused by radiation scattering and source leakage, a
      qualitative and quantitative analysis.
AB  - All irradiated objects in the vicinity of an imaging set-up increase the amount
      of scattered radiation. It is a well-known fact that if this radiation is allowed
      to impinge on the image collector it naturally degrades the image quality. It
      also causes problems with equipment characterisation, such as X-ray energy
      spectra measurements. However, it may not be a well-known fact that when a small
      radiation safety enclosure is used - common for industrial applications - this
      type of scattered radiation is astonishing large. In this work a quantitative and
      qualitative analysis has been carried out in an attempt to explain the origin of
      the problem, why it occurs and how it may be treated.The scattered radiation
      increases rapidly when the fractions of X-ray photons in the primary X-ray
      spectrum above the K-edges of the enclosure wall material increase. High-energy
      photons are scattered and/or will generate characteristic radiation in the
      enclosure wall material instead of being absorbed. For lead, which is commonly
      used as shielding and wall material, this noise becomes significant when tube
      potentials over 90-100 kV are used, since the K-edges for lead are 72-74 keV
      (Kalpha) and 85-87 keV (Kbeta). Below tube potentials of 100 kV, the noise from
      scattered radiation is insignificant, even if the primary beam is wide enough to
      hit the enclosure walls. Above 100 kV it increases rapidly and for this
      application the number of scattered photons was 50% of the primary photons at 170
      kV.In this particular case this problem was accentuated above tube potentials of
      100 kV since the steel housing of the micro focal X-ray source used was
      penetrated by high-energy photons in unwanted directions. Collimation of the X
      ray beam just in front of the X-ray source output window to narrow the solid
      angle of the primary X-ray beam to avoid direct radiation of the enclosure walls
      was not enough to suppress this scattered noise. A wider X-ray shield, covering
      the entire front of the X-ray source had to be applied. Other solutions to
      decrease scattered radiation would be the following: Increased internal shielding
      of the X-ray source is the first choice if the same possibilities for geometrical
      magnification of the imaged object are to be maintained. Increased distances to
      the enclosure walls and other objects inside, that is, to use larger enclosures
      or even separate X-ray chambers would also decrease scattered radiation. To line
      the enclosure with a series of X-ray shielding materials with K-edges at lower
      and lower energies is another alternative. The lowest K-edge material should be
      placed closest to the detector followed by the second lowest K-edge material
      etc., to effectively absorb backscatter and characteristic radiation from the
      enclosure walls. This would, however, be a rather expensive and complicated
      solution.

PMID- 22388425
TI  - Modelling of an X-ray image-intensifier-based radiography system.
AB  - A model will be proposed for predicting the expected value and variance of the
      measured signal-level in collected radiographic images obtained with an image
      intensifier-based X-ray radiography system. The model parameters are determined
      from both theoretical and experimental data and incorporate all parameters that
      can be varied by the system operator, except CCD-camera readout rate. The
      proposed model predicts the expected value and variance of the grey-level in the
      output image with high accuracy. It is also shown that it is very important to
      compensate for the inhomogeneous pixel sensitivity when comparing the variance of
      the signal-level in a pixel from sequentially collected images with the variance
      determined in a single image.

PMID- 22388426
TI  - Optimised detail detectability in computerised tomography.
AB  - It is of interest to know the minimum discernible detail size when performing non
      destructive testing with high-resolution computerised tomography. But it is
      difficult to empirically find optimal parameter settings that maximise
      detectability for each individual imaging task. In this work a method to
      determine the optimal performance for a high-resolution computerised tomography
      system has been developed. It reveals the detectability limit for specific
      contrasting details in terms of imaged object diameter when the signal-to-noise
      ratio, SNRDeltaS,CT, between the contrasting detail and its surroundings has been
      maximised using optimal data collection parameter settings.This work includes
      modelling and verification of the total unsharpness of the CT-system in terms of
      modulation transfer-function, MTF. Together with the limiting perception factor
      and maximised SNRDeltaproj in the CT projection data, the detectability limits
      for any specific contrasting detail are determined as a function of imaged object
      material and geometry. Maximised SNRDeltaproj was obtained by optimising the
      parameters: X-ray source tube potential, X-ray filter, exposure time and optical
      aperture. The importance of using optimal settings when performing CT
      investigations, especially when investigating objects with large diameters, is
      demonstrated.It was found that it is possible to predict the detectability for
      any specific contrasting detail. It was also discovered that the optimal settings
      for a given object diameter and material are dependent on the detail material. In
      some cases an improvement of the detail signal-to-noise-ratio was obtained by
      using a combination of X-ray filter materials. It was also found that
      SNRDeltaproj is very sensitive to the thickness of denser X-ray filter materials
      (higher atomic number and density).

PMID- 22388427
TI  - Correction for beam hardening artefacts in computerised tomography.
AB  - Conventional computerised tomography systems (CT) are usually equipped with
      polyenergetic X-ray sources, which prevents accurate density measurements because
      of the general CT-image artefact called beam hardening (BH). BH results in false
      gradients of the linear attenuation coefficient in the CT cross section images,
      indicating a non-existent density or composition gradient in the imaged object. A
      number of methods have been proposed to correct for, or limit the effect of, beam
      hardening. One of these is called linearisation of the CT-data, in which the
      polyenergetic CT-data are transformed to monoenergetic CT-data. This requires
      knowledge of the CT-data as a function of object thickness. Data points to derive
      this function are usually measured using a set of samples of different object
      material thicknesses at the imaging parameter settings used and fitted with a
      polynomial. However, the sample preparation makes this method tedious to use. In
      this work a simulation method has been developed, which can accurately simulate
      the polyenergetic CT-data for any arbitrary object material and thickness if a
      priori information of the object material density and composition exists. The
      simulation method requires detailed knowledge of the imaging system, that is, X
      ray energy spectra, detector response and information transfer from detector to
      digitised data. Besides developing the simulation tool, it has been shown that
      one of the major difficulties with this BH-correction method is to accurately
      determine the curvature of the function representing the polyenergetic CT-data.
      Earlier proposed endorsements to fit a second-degree polynomial to the
      polyenergetic CT-data are not sufficient to describe its curvature, at least a
      polynomial of degree eight or higher is required. Here cubic-spine interpolation
      is used, which avoids the problem.

PMID- 22388440
TI  - An unexpected disproportional reaction of 2H-azirines giving (1E,3Z)-2-aza-1,3
      dienes and aromatic nitriles in the presence of nickel catalysts.
AB  - An unprecedented nickel-catalysed disproportional reaction of 2,3-diaryl-2H
      azirines forming azabutadienes and aromatic nitriles was discovered. This
      reaction involves the cleavage of two bonds of the 2H-azirine framework, which
      provides a novel type of transformation of 2H-azirines.

PMID- 22388442
TI  - From the Editor-in-Chief.

PMID- 22388441
TI  - A spectrum of morphologic lesions of focal segmental glomerulosclerosis by
      Columbia criteria in human immunodeficiency virus infection.
AB  - The Columbia working classification of focal segmental glomerulosclerosis (FSGS)
      identifies five types of glomerular lesions, designated collapsing (COLL),
      cellular (CELL), glomerular tip lesion (GTL), perihilar (PH), and not otherwise
      specified (NOS) variant lesions. FSGS COLL and non-collapsing variants of FSGS
      are described in human immunodeficiency virus (HIV)-associated kidney disease.
      This study examined the range and relationships of Columbia-type segmental
      sclerosing lesions in biopsies from patients with HIV infection. We identified 47
      renal biopsies from 46 patients with HIV infection obtained over an 8-year
      period. Twenty-seven biopsies from 26 patients had FSGS. Sixteen biopsies had
      FSGS COLL (59.3%), 3 had CELL (11.1%), 5 had NOS (18.5%), 2 had PH (7.4%), and 1
      had GTL (3.7%) by the Columbia classification. Biopsies had more than one type of
      Columbia FSGS lesion in 63% and one type in 37%. Single types of FSGS lesions
      were identified in eight of eight biopsies with <=10 glomeruli. Combinations of
      lesions were observed in 17 of 19 (89.5%) with >10 glomeruli, and the coincidence
      of COLL, CELL, and NOS lesions was not random. NOS, COLL, and CELL morphologic
      lesions of FSGS frequently coexist in kidney biopsies from HIV+ patients.
      Combined patterns of FSGS suggest that lesions identified by Columbia criteria
      may be part of a spectrum of responses to injury in the setting of HIV infection.

PMID- 22388443
TI  - Meniscal injuries: A critical review.
AB  - Although once perceived as an unimportant vestigial structure, the menisci of the
      knee are now known to be a common source of knee pain and disability. The medial
      meniscus is more vulnerable to injury to due to its intimate attachment to the
      medial collateral ligament. The moveable lateral meniscus is less prone to tear
      except when the ACL is injured. The medial and lateral menisci are usually
      injured as a result of sudden knee flexion with a component of knee internal or
      external rotation. However, older patients may present without a specific
      mechanism of injury as their meniscal injuries are often due to degenerative
      processes. Most meniscal injuries can be diagnosed with a thorough physical
      examination utilizing the McMurray, Apley, and ''bounce home'' maneuvers. Joint
      line tenderness and the presence of a knee effusion aid in the diagnosis.
      Magnetic Resonance Imaging (MRI) has become the test of choice in confirming
      injury. MRI also defines the type, location, and severity of meniscal injury.
      Some meniscal injuries, particularly peripheral, well-vascularized tears, may be
      more prone to healing with nonsurgical management. Typical initial management
      includes reduction of swelling and pain. Rehabilitation stresses tri-planar
      functional retraining. The final phases of rehabilitation incorporate a
      functional progression to sports or work specific activities. Arthroscopic knee
      surgery has become a prevalent treatment method for bucket handle tears and non
      vascularized meniscal injuries. Meniscal repair is currently preferred over
      partial menisectomy to avoid premature osteoarthritis. In sum, clinicians can
      return patients with meniscal pain to a high level of function with appropriate
      recognition of injury and functional rehabilitation.

PMID- 22388444
TI  - A review of three commonly prescribed skeletal muscle relaxants.
AB  - Skeletal muscle relaxants (SMR) are commonly used drugs prescribed for the
      treatment of muscle spasm and discomfort. Although many have been in use for
      decades, physicians may be unaware of the accumulating evidence of their risks,
      benefits, safety and side effects. This review examines the efficacy, side
      effects, and safety of three commonly prescribed SMRs: metaxalone,
      cyclobenzaprine, and carisoprodol. All three appear to have equal efficacy, but
      their side effects vary considerably. Metaxalone has the fewest reports of side
      effects, and no reports of major safety issues. Cyclobenzaprine, closely related
      to the tricyclic antidepressants, causes the expected lethargy and
      anticholinergic side effects, and may have some toxicity in overdose and in
      combination with other substances. Carisoprodol raises the greatest concern.
      Reports in the literature suggest a significant potential for physical and
      psychological dependence perhaps suggesting a potential for misuse. It also has,
      perhaps, the greatest toxicity. A secondary goal of this review is to stimulate
      more discourse about these commonly used, but poorly understood compounds.

PMID- 22388445
TI  - Rehabilitation of long-term sick-listed patients in Sweden through techniques of
      sports medicine.
AB  - Sweden has seen a sharp increase in sick-listing recently. A new rehabilitation
      programme was tested for patients with musculoskeletal pain applying the
      experiences from sports injury rehabilitation. In this programme, the danger of
      inactivity was emphasised, and the staff accepted that the process of restoring
      physical fitness may be accompanied by a temporary increase in pain. During an 11
      month period, 101 patients began a 4-week rehabilitation programme. This
      programme was in action 5 days a week from 9AM to 4PM. Six patients broke off the
      programme. The remainder were called back for a follow-up 6 months later, a total
      of 83 patients attending. This follow-up showed that only 22% benefit.
      Significantly more men than women returned to work. After rehabilitation the
      patients perceived better health and their living habits normalized. In patients
      sick-listed for long periods, an intensive period of exercise based largely on
      sports medicine can lead to return-to-work, also in Sweden.

PMID- 22388446
TI  - Neuromagnetic treatment of pain in refractory carpal tunnel syndrome: An
      electrophysiological and placebo analysis.
AB  - {?it OBJECTIVE: } To evaluate the neurobiological effect of constant,
      subthreshold magnetic field exposure on symptomatic median nerve compression
      symptoms, neurophysiology and assess the role of placebo. {?it BACKGROUND: }
      Conservative treatment of moderate and severe CTS has been variable and often
      results in surgical decompression at the wrist. {?it DESIGN/METHODS: } Eight
      moderately symptomatic and intractable CTS hands constantly wore identical
      Elastomag wrist support wraps (unmagnetized vs. magnetized 350 gauss) for one
      month intervals. Identical wraps were then switched at the second month. Baseline
      assessments included the neurological exam, VAS scores for burning, numbness and
      tingling twice a day on a 10 point ordinal scale. CMAP/SNAP was determined at
      baseline and monthly intervals. Clinical follow-up at end of fourth and eighth
      weeks was compared to baseline. {?it RESULTS: } The mean pain scores improved in
      four patients (57%) which also correlated with clinical benefit. Improvement in
      Tinel and Phalen sign as well as sensory changes was similarly noted. Placebo
      effect was detected in one patient (13%). Electrophysiological improvement in
      distal latencies in 5/8 hands using magnetic treatment was noted compared to no
      change or worsening in all placebo cases. {?it CONCLUSIONS: } Percutaneous
      magnetic stimulation induced palliative pain relief, presumably via modulation of
      the unmyelinated C-fibers. Prior studies have suggested an influence on K+ inward
      rectification excitability. These observations suggest that wearing magnetized
      wrist wraps appears to be a novel therapeutic agent. However, the underlying
      neuropathology tends to be progressive.

PMID- 22388447
TI  - Chronic cervical myofascial pain syndrome: Improvement in dizziness and pain with
      a multidisciplinary rehabilitation program. A pilot study.
AB  - PURPOSE: The purpose of this retrospective, pilot study was to assess changes in
      dizziness, pain and function in subjects undergoing an outpatient rehabilitation
      program focusing on cervical pain. METHODS: Fifteen subjects with chronic
      cervical myofascial pain and concurrent dizziness of suspected cervical origin
      completed a retrospective questionnaire. Improvement in pain, dizziness and
      function were recorded on a visual analog scale (VAS) in response to a non
      standardized rehabilitation program involving modalities, stretching,
      strengthening, trigger point injections and aerobic conditioning. RESULTS:
      Subjects reported an average VAS improvement in dizziness of 59% (+/-29%), pain
      69% (+/-21%) and function 71%(+/-19). Seven subjects experienced reproduction of
      their dizziness and pain during trigger point injections. Overall, twenty seven
      percent reported no further episodes of dizziness. All subjects experienced a
      decrease in the frequency of episodes of dizziness. There was a correlation
      between dizziness and pain (r = 0.58), dizziness and function (r = 0.60), and
      pain and function (r = 0.74). CONCLUSION: Subjects with dizziness and cervical
      myofascial pain of suspected cervical origin may experience symptomatic and
      functional improvement through a rehabilitative program addressing their cervical
      pain. Future prospective, randomized controlled studies are needed to address
      which intervention is the most effective.

PMID- 22388448
TI  - Traumatic sciatic nerve contusion.
AB  - A case of isolated post-traumatic sciatic nerve contusion is reported, sustained
      after direct blunt trauma to the region of the buttock after a fall. Evaluation
      of this nerve injury not only included an EMG/ NCS, but also confirmatory
      evidence was obtained using the Minor's iodine-starch test to detect disturbances
      of sweat secretion. This case of sciatic nerve contusion responded to stimulator
      guided local steroid injections. Cross-sectional anatomy of the sciatic nerve and
      various etiologies of sciatic nerve neuropathy is revisited.

PMID- 22388449
TI  - A pilot study of pain management during rehabilitation for hip and knee
      arthroplasty.
AB  - {?it OBJECTIVE: } To evaluate the efficacy of pain management in a clinical
      pathway for rehabilitation after hip and knee arthroplasty, in which scheduled
      medications are rapidly tapered and prn medications are continued throughout the
      inpatient stay. {?it STUDY DESIGN: } A prospective cross-sectional study. {?it
      SETTING: } General rehabilitation unit of a regional acute rehabilitation center.
      {?it PATIENTS: } Twenty-nine patients admitted consecutively to the
      rehabilitation unit in three months. {?it OUTCOME MEASURES: } Number of pills/day
      of prn pain medication, pain scores at admission and discharge, frequency of
      constipation and nausea, Functional Independence Measure (FIM) gain, and length
      of stay (LOS). {?it RESULTS: } For all patients, prn pain medication use was 2.4
      pills/day/patient; the mean FIM gain was 22.1; and the average LOS was 9.8 days.
      In comparison to the Vicodin group, patients on Darvocet N-100 had significantly
      fewer requests for prn pain medication each day (3.1 vs. 1.1, p < 0.01),
      significantly better FIM gains better (18.9 vs. 24.1, p < 0.05), and fewer side
      effects (nausea and constipation). {?it CONCLUSION: } Choosing the right pain
      medication is imperative for achieving optimal efficiency in clinical pathways
      for orthopedic rehabilitation. In this pilot study, Darvocet N-100 is the
      preferred narcotic over codeine and its derivatives.

PMID- 22388450
TI  - Nanomedicine.

PMID- 22388451
TI  - Using intervention mapping as a participatory strategy: development of a cervical
      cancer screening intervention for Hispanic women.
AB  - Cervical cancer is preventable with treatment of precancerous lesions and
      treatable at early stages. Hispanics have higher rates of cervical cancer and
      lower rates of screening. Ayudando a las Mujeres con Informaccion, Guia, y Amor
      para su Salud (AMIGAS) is an intervention to increase cervical cancer screening
      in U.S. women of Mexican origin. AMIGAS was developed with the participation of
      the community using intervention mapping (IM). Following the IM process, the
      authors completed a needs assessment, development of program objectives,
      selection of intervention methods and strategies, and program design. A benefit
      of IM is its linkage with community-based participatory research as it includes
      engagement of community members to identify and refine priority areas. The
      success of this strategy suggests it a useful tool for other populations. The
      resulting intervention program is currently being tested for efficacy and cost
      effectiveness in three sites: El Paso, Texas; Houston, Texas; and Yakima,
      Washington.

PMID- 22388453
TI  - Bystander killing of malignant cells via the delivery of engineered thymidine
      active deoxycytidine kinase for suicide gene therapy of cancer.
AB  - Activity and specificity of chemotherapeutic agents against solid tumors can be
      augmented via the targeted or localized delivery of 'suicide' genes. Selective
      activation of specific prodrugs in cells expressing the 'suicide' gene drives
      their elimination by apoptosis, while also enabling the killing of adjacent
      bystander cells. Strong bystander effects can compensate for poor 'suicide' gene
      delivery, and depend on the prodrugs used and mechanisms for the acquisition of
      activated drug by the bystander population, such as the presence of gap
      junctional intercellular communications. Although a number of 'suicide' gene
      therapies for cancer have been developed and characterized, such as herpes
      simplex virus-derived thymidine kinase (HSV-tk)-based activation of ganciclovir,
      their limited success highlights the need for the development of more robust
      approaches. Limiting activation kinetics and evolution of chemoresistance are
      major obstacles. Here we describe 'suicide' gene therapy of cancer based on the
      lentivirus-mediated delivery of a thymidine-active human deoxycytidine kinase
      variant. This enzyme possesses substrate plasticity that enables it to activate a
      multitude of prodrugs, some with distinct mechanisms of action. We evaluated the
      magnitude and mechanisms of bystander effects induced by different prodrugs, and
      show that when used in combination, they can synergistically enhance the
      bystander effect while avoiding off-target toxicity.

PMID- 22388454
TI  - Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression
      in laryngeal carcinoma.
AB  - The purpose of this study is to develop a specific and efficient targeted gene
      therapy candidate approach for laryngeal carcinomas. Several promoters of human
      squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor
      (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for
      tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells
      by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest
      efficiency and specificity, and was used to control the expression of a
      recombinant active caspases-3 (revCasp3), which could trigger apoptosis without
      activation of its upstream cascade elements once expressed in a cell, in an
      adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In
      vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically
      expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase
      3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model,
      intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor
      growth without obvious loss of body weight and obvious hepatic toxicity. In
      summary, our study showed the specific and efficient apoptosis-inducing potential
      of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene
      therapy for laryngeal squamous cell carcinoma, which needs further systematic
      investigation.

PMID- 22388461
TI  - Synthesis of superparamagnetic Fe3O4/PMMA/SiO2 nanorattles with periodic
      mesoporous shell for lysozyme adsorption.
AB  - A new kind of nanorattle, composed of a Fe(3)O(4)/polymethyl methacrylate (PMMA)
      composite nanospherical core and mesoporous SiO(2) shell, has been successfully
      synthesized with the combination of a modified stober method and a dual-template
      strategy, followed by alcohol dialysis. The nanorattles showed high efficiency in
      protein adsorption and separation.

PMID- 22388452
TI  - Probing the Arabidopsis flagellin receptor: FLS2-FLS2 association and the
      contributions of specific domains to signaling function.
AB  - Flagellin sensing2 (FLS2) is a transmembrane receptor kinase that activates
      antimicrobial defense responses upon binding of bacterial flagellin or the
      flagellin-derived peptide flg22. We find that some Arabidopsis thaliana FLS2 is
      present in FLS2-FLS2 complexes before and after plant exposure to flg22. flg22
      binding capability is not required for FLS2-FLS2 association. Cys pairs flank the
      extracellular leucine rich repeat (LRR) domain in FLS2 and many other LRR
      receptors, and we find that the Cys pair N-terminal to the FLS2 LRR is required
      for normal processing, stability, and function, possibly due to undescribed
      endoplasmic reticulum quality control mechanisms. By contrast, disruption of the
      membrane-proximal Cys pair does not block FLS2 function, instead increasing
      responsiveness to flg22, as indicated by a stronger oxidative burst. There was no
      evidence for intermolecular FLS2-FLS2 disulfide bridges. Truncated FLS2
      containing only the intracellular domain associates with full-length FLS2 and
      exerts a dominant-negative effect on wild-type FLS2 function that is dependent on
      expression level but independent of the protein kinase capacity of the truncated
      protein. FLS2 is insensitive to disruption of multiple N-glycosylation sites, in
      contrast with the related receptor EF-Tu receptor that can be rendered
      nonfunctional by disruption of single glycosylation sites. These and additional
      findings more precisely define the molecular mechanisms of FLS2 receptor
      function.

PMID- 22388462
TI  - Water management challenges in the context of agricultural intensification and
      endemic fluorosis: the case of Yuanmou County.
AB  - Yuanmou County in Yunnan Province, China is situated in a dry hot valley where
      annual evaporation is almost six times the annual rainfall and thus the county
      suffers from chronic water shortages. Since the early 1980s the county has taken
      advantage of local warm climate and focused its economic development strategy on
      commercial vegetable plantations. This strategy successfully brings high income
      to the local government and farmers, but increases water consumption and adds an
      extra stressor to the already diminished water resources. Yuanmou County is one
      of the endemic fluorosis hotspots in China where both dental and skeletal
      fluorosis cases have been found among local villagers that were diagnosed as
      being water-borne. Despite measures to adapt to water shortages and control
      fluorosis taken by the local government and communities, new challenges are
      emerging. Herein, we describe the water management challenges facing the county
      as well as document the coping strategies adopted by the government and
      communities, analyze remaining and emerging challenges, and suggest an ecohealth
      framework for better management of water resources in Yuanmou.

PMID- 22388463
TI  - One-step synthesis of AgCl concave cubes by preferential overgrowth along <111>
      and <110> directions.
AB  - A new class of AgCl microstructures, concave cubes, with preferential overgrowth
      along <110> and <111> directions, has been prepared in a monodisperse fashion by
      a wet chemical oxidization method. With high-index facets exposed, the concave
      cubic AgCl exhibits higher photocatalytic activity in O(2) evolution than cubic
      ones.

PMID- 22388464
TI  - Fracture through a Harris growth arrest line:  a case report.
AB  - Fractures occur when bone is overloaded and mechanical failure occurs with the
      fracture propagating along the lines of least resistance. We report the case of a
      6-year-old boy who sustained a nondisplaced distal third tibial shaft fracture
      through a Harris growth arrest line of increased osseous density due to low
      energy blunt trauma. This case is used as an opportunity to review the literature
      on Harris growth arrest lines and discuss a fracture pattern that has not been
      previously described in the literature.

PMID- 22388465
TI  - Magnetic, electrochemical and spectroscopic properties of iron(III) amine
      bis(phenolate) halide complexes.
AB  - Eight new iron(III) amine-bis(phenolate) complexes are reported. The reaction of
      anhydrous FeX(3) salts (where X = Cl or Br) with the diprotonated tripodal
      tetradentate ligands 2-tetrahydrofurfurylamino-N,N-bis(2-methylene-4,6-di-tert
      butylphenol), H(2)L1, 2-tetrahydrofurfurylamino-N,N-bis(2-methylene-4-methyl-6
      tert-butylphenol), H(2)L2, and 2-methoxyethylamino-N,N-bis(2-methylene-4,6-di
      tert-butylphenol), H(2)L3, 2-methoxyethylamino-N,N-bis(2-methylene-4-methyl-6
      tert-butylphenol), H(2)L4 produces the trigonal bipyramidal iron(III) complexes,
      L1FeCl (1a), L1FeBr (1b), L2FeCl (2a), L2FeBr (2b), L3FeCl (3a), L3FeBr (3b),
      L4FeCl (4a), and L4FeBr (4b). All complexes have been characterized using
      electronic absorption spectroscopy, cyclic voltammetry and room temperature
      magnetic measurements. Variable temperature magnetic data were acquired for
      complexes 2b, 3a and 4b. Variable temperature Mossbauer spectra were obtained for
      2b, 3a and 4b. Single crystal X-ray molecular structures have been determined for
      proligand H(2)L4 and complexes 1b, 2b, and 4b.

PMID- 22388466
TI  - Ziprasidone versus clozapine in the treatment of psychotic symptoms in Parkinson
      disease:  a randomized open clinical trial.
AB  - OBJECTIVE: To compare the efficacy and safety of ziprasidone versus clozapine in
      patients with psychotic symptoms in Parkinson disease. METHODS: A 4-week,
      randomized, single-blind, open-label, parallel comparison of ziprasidone and
      clozapine was completed. Sixteen patients with Parkinson disease were included.
      Psychosis was assessed using the Brief Psychiatric Rating Scale (BPRS), and the
      Scale for the Assessment of Positive Symptoms (SAPS). The Unified Parkinson's
      Disease Rating Scale and the Abnormal Involuntary Movement Scale were used to
      assess motor conditions during the study period. Measures of drugs' adverse
      effects, white blood cell count, and the Clinical Global Impression Scale
      Severity Subscale were performed. Cognitive changes were assessed with the Mini
      Mental State Examination. RESULTS: Fourteen patients completed the study, 8
      patients on clozapine and 6 patients on ziprasidone. The final mean dosage for
      clozapine was 32.14 mg/d and that for ziprasidone was 35 mg/d. Throughout the
      study, neither the Unified Parkinson's Disease Rating Scale, the Abnormal
      Involuntary Movement Scale, or the Mini-Mental State Examination showed
      statistical differences in both groups. Psychotic symptoms, assessed with SAPS
      and BPRS, were reduced in both groups but with more intensity in the ziprasidone
      group (effect size in SAPS, 1.3, and effect size in BPRS, 1.7) than in the
      clozapine group (effect size in SAPS, 0.36, and effect size in BPRS, 0.53).
      CONCLUSIONS: Ziprasidone seems to be at least as effective as clozapine in the
      treatment to ameliorate psychotic symptoms in PD.

PMID- 22388467
TI  - The oblique supine decubitus position: technical description and comparison of
      results with the prone decubitus and dorsal supine decubitus positions.
AB  - Our objective was to analyze the advantages of the percutaneous nephrolithotomy
      in oblique supine decubitus compared to the prone and dorsal supine position. In
      87 patients diagnosed with urolithiasis (495.5-530.8 mm(2)), percutaneous
      nephrolithotomy (PNL) was performed from 2000 to 2011. The patients were divided
      into three groups: Group A, 32 patients, PNL in the prone decubitus position;
      Group B, 24 patients, PNL in the dorsal supine position; Group C, 31 patients,
      PNL in the oblique supine position. We analyzed intraoperative parameters,
      complications, and results among the three groups. The three procedures were
      performed with a single access, 24-30 Ch. No statistically significant
      differences were found among the three groups regarding the patients'
      characteristics, or the morphology or size of the kidney stone treated. The
      operation time was shorter in the cases of PNL in dorsal supine and oblique
      supine compared to the prone position. The complication rate was very similar in
      the three groups. The main advantage of the PNL in oblique supine compared to the
      dorsal supine was that the puncture could in all cases be directed by
      ultrasonography, with greater precision, more safety, and more control of the
      percutaneous renal access. The oblique supine decubitus position is a safe
      position for the percutaneous treatment of urolithiasis and it becomes easier
      when the puncture is guided by ultrasound.

PMID- 22388468
TI  - Resolution determination in X-ray microscopy: an analysis of the effects of
      partial coherence and illumination spectrum.
AB  - Determining the resolution of a zone plate X-ray microscope is a complicated
      issue, depending on many factors in addition to the quality of the optic. These
      include the degree of coherence of the illumination, the illumination spectrum,
      and the nature of the resolution test object. In this paper, we examine closely
      how the degree of coherence of the illumination affects the resolution as
      measured with three typical test patterns. In addition, we determine the extent
      to which the illumination spectrum affects the resolution. We compare X-ray
      microscope test images to numerical simulations as a function of coherence and
      illumination spectrum. We are able to conclude that in these experiments, the
      resolution of the X-ray microscope is 41 nm, or 40% discrepancy is due to
      aberrations in the objective zone plate lens.

PMID- 22388469
TI  - Imaging soft X-rays with opaque spheres.
AB  - Images of small fluorescence X-ray sources obtained by diffraction with opaque
      spheres were recorded with a flow-proportional counter and on X-ray sensitive
      film. Image fluxes and intensities obtained experimentally were compared with
      theoretical estimates made using analytical expressions derived from the sphere's
      point-source imaging properties.

PMID- 22388470
TI  - Radiation exposure in a modern, circularly scanned-beam laminographic X-ray
      inspection system.
AB  - Circularly scanned-beam laminography is currently the predominant technique used
      for the nondestructive examination of printed circuit solder assemblies via cross
      sectional X-ray imaging. Given industry trends towards double-sided assemblies
      and limited access components, cross-sectional X-ray inspection is furthermore
      becoming increasingly important. Use of X-rays for inspection of solder joints on
      loaded printed circuit boards nonetheless often leads to concern surrounding
      possible undesirable radiation effects on the circuitry mounted on the board. In
      this paper we develop a simple analytical model useful for predicting the
      radiation exposure rates in a scanned-beam laminography system. We demonstrate
      the validity of the model through a series of dosimetry experiments.

PMID- 22388471
TI  - Characterization of X-ray contact microscopic imaging in keV spectral region
      using laser produced plasmas.
AB  - An experimental study is performed of soft X-ray emission from laser produced
      plasmas for single shot X-ray contact microscopic imaging of physical and
      biological microstructures. Planar copper targets are irradiated by 10 J, 28 nS
      Nd:glass laser pulses in the intensity range of 1011 W/cm2 to 3 * 1012 W/cm2.
      Measurements of keV X-ray emission viz. X-ray intensity scaling with laser
      intensity, X-ray source size, X-ray conversion efficiency and exposure dose on
      the sample are presented. Fine copper grids of 70 mm mesh size and 10 mm
      thickness are used as test samples for imaging on ERP-40 photoresist. A spatial
      resolution of ~195 nm is observed, consistent with theoretical estimate
      considering the contribution of geometrical and diffraction blurring, and
      statistical noise of photons incident on the sample. This study should be useful
      in proper selection of source parameters for optimization of spatial resolution
      in single shot keV contact imaging.

PMID- 22388472
TI  - X-ray lens of monolithic polycapillaries for macromolecular crystallography.
AB  - The monolithic polycapillary X-ray Lens is a fast developing optics that has many
      applications in different fields, one of them, described in this paper, is a
      successful application in the X-ray diffraction for macromolecular
      crystallography. The direct beam intensity irradiating on crystal with usage of
      the monolithic X-ray lens was increased 1 to 2 order of magnitude more than the
      traditional method with the double focusing mirrors. the diffracted X-ray
      intensity was increased more than about 8 times, the resolution was improved by
      0.2?0.6A, and the signal to noise ratio was also improved. The measuring time
      became shorter. The crystal samples which had to be analyzed by synchrotron
      before are able to be investigated in routine laboratory now.

PMID- 22388473
TI  - What's it worth? Public willingness to pay to avoid mental illnesses compared
      with general medical illnesses.
AB  - OBJECTIVE: Allocation of resources for the treatment of mental illness is low
      relative to the burden imposed by these illnesses. The reason for this
      discrepancy has not been established. Few studies have directly and
      systematically compared public evaluations of the importance of treating mental
      illnesses and general medical illnesses. This study assessed public willingness
      to pay for treatments of mental health conditions and of general medical
      conditions to determine whether willingness to pay less for mental health
      treatments is due to the perception that mental health conditions are less
      burdensome. METHODS: U.S. adults (N=710) in a nationally representative sample
      were provided with descriptions of two mental and three general medical
      illnesses. Respondents rated their willingness to pay to avoid each illness and
      then their perception of the burdensomeness of each illness. RESULTS:
      Participants rated the two mental illnesses as relatively more burdensome than
      the general medical illnesses, but the amount they were willing to pay to avoid
      the mental illnesses was lower. Specifically, participants were willing to pay
      40% less to avoid the mental illnesses compared with the general medical
      conditions, for a comparable benefit in terms of quality of life. CONCLUSIONS:
      Even though respondents recognized that severe mental illnesses can dramatically
      lower quality of life, they were less willing to pay to avoid such illnesses than
      they were to pay to cure less burdensome general medical illnesses.

PMID- 22388474
TI  - Longitudinal trends in using physical interventions to manage aggression and self
      harm in mental health services.
AB  - OBJECTIVES: Repetitive aggression by a patient receiving mental health inpatient
      care is likely to elicit various patterns of response from care staff over time.
      This study sought to examine patterns of coercive physical intervention in
      relation to repeated episodes of aggression by particular patients. METHODS: A
      data set of 9,945 aggression and self-harm incidents over a five-year period in
      one mental health service in England was constructed. Incidents by a specific
      individual were categorized according to their position in a sequence (first,
      second, and so on) and by the use of physical intervention by staff to manage the
      incident. RESULTS: Trends in the use of physical intervention varied across
      settings. There was a significant tendency in general (nonforensic) services for
      use of physical intervention to increase in response to physical aggression
      (physical intervention in first versus subsequent incidents: odds ratio [OR]=.69,
      95% confidence interval [CI]=.54-.90) and to decrease in response to threats
      (physical intervention in first threat versus subsequent threats: OR=1.62,
      CI=1.09-2.39). CONCLUSION: There were significant trends over time in the use of
      physical intervention to manage violence and self-harm. However, the dynamics
      behind this finding will remain unclear without further research.

PMID- 22388475
TI  - Consumer-providers in assertive community treatment programs: associations with
      client outcomes.
AB  - OBJECTIVE: This study examined whether employing mental health consumers as
      consumer-providers in assertive community treatment teams can enhance outcomes
      for clients with severe mental illness. METHODS: In a prospective longitudinal
      study, presence of consumer-providers and outcomes of 530 clients with severe
      mental illness in 20 outpatient teams were assessed at baseline and at one-year
      and two-year follow-ups. Measures included the Health of the Nation Outcome
      Scales (HoNOS), the Camberwell Assessment of Need Short Assessment Schedule
      (CANSAS), the Working Alliance Scale, the number of hospital days, and the number
      of days of homelessness. Multilevel regression was used with the independent
      variables consumer-provider presence, time of measurement, and their interaction.
      RESULTS: A positive association was found between consumer-provider presence and
      improvements in functioning on the HoNOS (p = .020), met needs in relation to
      personal recovery (p=.044), unmet needs in relation to personal recovery (p =
      .008), and number of homeless days (p<.001). A negative association was found for
      consumer-provider presence and the number of hospital days (p = .019).
      CONCLUSIONS: Consumer-providers are important participants in outpatient teams
      serving clients with severe mental illnesses, although integrating these
      providers as part of a team is a slow process.

PMID- 22388476
TI  - Effects on children of treating their mothers' depression: results of a 12-month
      follow-up.
AB  - OBJECTIVE: This study used a controlled research design to examine the effects on
      children of treating their mothers' depression and of remission of the mothers'
      depression. METHOD: The sample consisted of 60 low-income women with major
      depression, who were predominantly from minority racial-ethnic groups, and their
      children ages four to 11. Women were randomly assigned to receive one of two
      active treatments (medication or cognitive-behavioral therapy) or a referral to
      existing community services. The mothers' depression was assessed by self-report
      on the Hamilton Depression Rating Scale, and the children's symptoms and adaptive
      skills were assessed by their mothers at baseline and six-month and 12-month
      follow-ups with the Behavior Assessment System for Children. RESULTS: Mixed
      effects random intercept and random slope repeated-measures analyses using an
      intent-to-treat approach indicated that active treatment of mothers did not
      result in improvement in their children's behavior problems or adaptive skills.
      However, at both the six- and the 12-month follow-ups, children of mothers whose
      depression had remitted, regardless of treatment assignment, had significantly
      fewer behavior problems than children whose mothers remained depressed.
      CONCLUSIONS: The results support the need to expand access to, and support
      participation in, depression treatment among low-income women from minority
      racial-ethnic groups. Although treatment alone of this undertreated population
      was not associated with improvement in children's outcomes, it is a necessary
      first step to prevent psychopathology among offspring of depressed parents.

PMID- 22388477
TI  - Combining biomedical accounts of mental disorders with treatability information
      to reduce mental illness stigma.
AB  - OBJECTIVE: Biomedical accounts of mental disorders are increasingly prevalent but
      can yield pessimism about prognosis and fail to reduce stigma. The authors tested
      whether information emphasizing the treatability of mental disorders could reduce
      stigma by contradicting the prognostic pessimism associated with biological
      attributions. METHODS: A total of 249 participants recruited online read
      vignettes about two individuals--one with schizophrenia and one with borderline
      personality disorder. The vignettes attributed the disorders to biological or
      nonbiological causes and did or did not include information about treatment.
      Participants' attitudes toward the individual were assessed with social distance
      scales. RESULTS: Participants who received information about treatment had more
      positive attitudes toward the individual described in the vignette if the
      disorder was attributed to a biological cause, but treatment information had no
      such effect if the disorder was attributed to a nonbiological cause. CONCLUSIONS:
      Combining biomedical accounts of psychopathology with information about treatment
      appears to be an effective destigmatization approach.

PMID- 22388481
TI  - Living radical polymerization of acrylates and acrylamides mediated by a
      versatile cobalt porphyrin complex.
AB  - Living radical polymerization (LRP) of organic and water soluble acrylates and
      acrylamides was mediated by a versatile cobalt porphyrin complex (TMP-OH)Co. The
      capability of this cobalt complex to mediate LRP in both polar and non-polar
      media permits the direct synthesis of useful and previously difficult to prepare
      functional block copolymers.

PMID- 22388478
TI  - Prevention of beta-amyloid degeneration of microglia by erythropoietin depends on
      Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL.
AB  - Central nervous system microglia promote neuronal regeneration and sequester
      toxic beta-amyloid (Abeta) deposition during Alzheimer's disease. We show that
      the cytokine erythropoietin (EPO) decreases the toxic effect of Abeta on
      microgliain vitro. EPO up-regulates the cysteine-rich glycosylated wingless
      protein Wnt1 and activates the PI 3-K/Akt1/mTOR/ p70S6K pathway. This in turn
      increases phosphorylation and cytosol trafficking of Bad, reduces the Bad/Bcl-xL
      complex and increases the Bcl-xL/Bax complex, thus preventing caspase 1 and
      caspase 3 activation and apoptosis. Our data may foster development of novel
      strategies to use cytoprotectants such as EPO for Alzheimer's disease and other
      degenerative disorders.

PMID- 22388479
TI  - Distinct characteristics of single starch-binding domain SBD1 derived from tandem
      domains SBD1-SBD2 of halophilic Kocuria varians alpha-amylase.
AB  - Kocuria varians alpha-amylase contains tandem starch-binding domains SBD1-SBD2
      (SBD12) that possess typical halophilic characteristics. Recombinant tandem
      domains SBD12 and single domain SBD1, both with amino-terminal hexa-His tag, were
      expressed in and purified to homogeneity from Escherichia coli. The circular
      dichroism (CD) spectrum of His-SBD12 was characterized by a positive peak at 233
      nm ascribed to the aromatic stacking. Although the signal occurred in the far UV
      region, it is an indication of tertiary structure folding. CD spectrum of single
      domain His-SBD1 exhibited the same peak position, signal intensity and spectral
      shape as those of His-SBD12, suggesting that the aromatic stacking must occur
      within the domain, and that two SBD domains in SBD12 and SBD1 has a similar
      folded structure. This structural observation was consistent with the biological
      activity that His-SBD1 showed binding activity against raw starch granules and
      amylose resin with 70-80% efficiency compared with binding of equimolar His
      SBD12. Although the thermal unfolding rate of SBD12 and SBD1 were similar, the
      refolding rates of SBD12 and SBD1 from thermal melting were greatly different:
      His-SBD12 refolded slowly (T(1/2) = ~84 min), while refolding of single domain
      His-SBD1 was found to be 20-fold faster (T(1/2) = 4.2 min). The possible
      mechanism of this large difference in refolding rate was discussed. Maltose at 20
      mM showed 5-6  degrees C increase in thermal melting of both His-SBD12 and His
      SBD1, while its effects on the time course of unfolding and refolding were
      insignificant.

PMID- 22388482
TI  - Affordably priced new drugs for poor populations: Approaches for a global
      solution.
AB  - A very large proportion of the world's population, particularly the poor in
      developing countries, still have insufficient access or none at all to treatment
      with essential drugs. This situation can arise with any drug and for various
      reasons, but it exists in extreme form where the drug is irreplaceable yet
      entirely unaffordable. That is the case with new or relatively recent drugs which
      could save lives or eradicate endemic disease, but which (particularly during
      their period of patent protection) are usually sold at prices higher than
      patients or their community can afford to pay. The consequences of this situation
      in terms of persistent illness, suffering and large-scale mortality are felt most
      immediately in the developing world, but because today disease travels so rapidly
      it represents a threat to the world as a whole. As of late 2001, only a number of
      limited ad hoc solutions to these problems have emerged. They have provided
      relief in a number of specific situations but they offer no guarantee of
      permanence, are applied mainly at the discretion of multinational companies or
      aid agencies and leave the bulk of the global problem unchanged. The problem must
      be capable of a broad and lasting solution since the basic costs of manufacturing
      and distributing most of the drugs in question are not in themselves prohibitive.
      High prices are primarily a consequence of the need to provide an adequate return
      on investment, to finance research and development, and to pay the very high
      costs of promotion in intensively competitive markets. At present, however, these
      secondary costs are almost entirely covered by the sales income from
      industrialized countries, and that is unlikely to change. In the developing
      world, where the sales of such drugs has been negligible, it must be possible to
      supply them in more adequate quantities, at a fair and affordable prices which
      are very close to the basic manufacturing and distribution costs. This will
      require an innovative commercial approach but it may not demand a sacrifice; in
      many instances it will be the key to opening new emergent markets where low
      profit margins can be outweighed by high unit sales. The feasibility of sharply
      differential pricing for drugs has indeed been demonstrated already in various
      countries and regions where specific agreements for low-cost supply have operated
      successfully, for example, for vaccines and contraceptives but also for some
      therapeutic drugs still protected by patent. If this type of approach can be
      extended so that important new drugs are as a matter of routine made available to
      developing countries at highly preferential prices it would contribute greatly to
      the solution of major health problems. Naturally a number of safeguards are
      necessary. The most important of these is that drugs sold at "minimal" prices to
      a developing country must not leak across its borders to be re-sold at a profit
      elsewhere. Experience with vaccine and contraceptive agreements shows that this
      risk can be virtually eliminated, although the parallels with therapeutic drugs
      are not exact and the possibility of theft and "leakage" might be greater with
      such items, especially where they have a high potential market value. Nor must a
      drug, which enters a developing country at a preferential price then be burdened
      by taxes, customs duties or excessive wholesale or retail profit margins that
      might again put it out of reach of those who need it. Again, one would not wish
      to discourage the further evolution of good-quality drug manufacturing in
      developing countries, which is already making an important contribution to health
      and to the national economy. Safeguards on these and other matters could well be
      incorporated into a global working agreement between all parties, seeking to
      define and promote the use of minimum-level pricing for vital new drugs. That
      agreement would be implemented through specific arrangements and unilateral
      initiatives of an already familiar type; these would be centrally registered and
      monitored, as would situations of ongoing need. In this way, activities could be
      better attuned to need, progress assessed and the entire situation rendered
      transparent.

PMID- 22388483
TI  - The role of drug donations on hospital use of antibiotics during the war and
      postwar period.
AB  - Using ATC/DDD methodology, we analyzed antibiotic utilization in the Clinical
      Centre of Banja Luka, one of the largest clinical centres in Bosnia and
      Herzegovina, during the war and postwar period (1994-2000), as well as the role
      of drug donations on doctors' prescribing decisions. The retrospective analysis
      of antibiotic utilization (group J according to the Anatomical Therapeutical
      Chemical - ATC classification) was based upon the data provided from the hospital
      computer centre and calculated as the number of defined daily doses (DDD) per 100
      bed days. The pharmacoepidemiological analysis showed that the total use of
      antibiotics changed markedly; in the war year of 1994, as well as in 1998,
      antibiotics were the second most frequently used group of drugs (19.7% and 14.1%
      of total drug utilization respectively), while in the following years antibiotics
      were considerably less used. These dynamics were significantly influenced by drug
      donations, the percentage of which in the overall antibiotic supply in 1996 was
      91.5%, while in 1999 and in 2000 it decreased considerably to 46.8% and 45.6%,
      respectively. The most widely prescribed antibiotics were penicillins,
      aminoglycosides, sulphonamides and tetracyclines. Among these, the
      aminopenicillins, co-trimoxazole, gentamicin and tetracyclines were mainly (70
      100%) supplied as a drug donations. However, macrolides, cephalosporins and
      quinolones were less used due to fact that they were considerably less often
      delivered through drug donations. It can be concluded that the drug donations had
      a significant impact on prescribing practice and the rational use of antibiotics
      in the Clinical Centre studied.

PMID- 22388484
TI  - Patient-risk due to negligence by Locum General Practitioners outside of office
      hours.
AB  - In Holland, first tier medical care outside of office hours is provided by
      regular GP's acting as Locum GP's. On several occasions concerns have been
      expressed about Locum GP's not visiting the patient when necessary. The number of
      complaints against Locum GP's submitted to the Medical Boards has been increasing
      over time and relate in particular to refusals of Locum GP's to visit the
      patient. In many of these cases the patient died. The paper develops a
      quantitative estimate of the risk for the patient due to negligence of Locum
      GP's. The measure of the risk is taken as the number of patients who died
      unnecessarily due to negligence of Locum GP's as determined by the Medical
      Boards. The paper estimates that in Holland in the year 2000 about 1500 patients
      would probably not have died had the Locum GP's working out-of-hours not been
      negligent by contravening professional standards. In more than half of these
      cases the Locum GP's did not visit the patient, or did not visit the patient in
      time, when necessary. This level of patient risk must be regarded as socially
      unacceptable. One important explanation for these accidents could be that doctors
      are largely unfamiliar with the professional standards developed by the Medical
      Boards. Because of the assumptions made and the uncertainty regarding the data
      used, the actual numbers of these accidents may be higher or lower than estimated
      here. Although more reliable data will allow the results to be determined more
      reliably, this is unlikely to change the acceptability of the risk.

PMID- 22388485
TI  - Psychosocial consequences of screening for albuminuria and certain other risk
      factors.
AB  - OBJECTIVE: To gain insight into the psychosocial consequences of a screening
      programme on the progression of heart, vascular and kidney damage. DESIGN: Over
      85,000 people aged 28-75 were invited to participate in a screening for
      albuminuria. Nearly half of them sent in their morning urine of which almost
      10,000 had a (slightly) elevated urinary albumin level. This latter group was
      invited to participate in a follow-up screening (24-hour urine samples, blood
      pressure, glucose, cholesterol) together with +/-3,000 randomly selected subjects
      with a normal urinary albumin concentration. A questionnaire on the psychosocial
      consequences of the screening was sent to 335 participants of the screening
      programme each of whom had received their (positive or negative) screening
      results two weeks previously. RESULTS: The response rate was 75%. A minority of
      the respondents, diagnosed for risk factors, expressed some concern. No influence
      on the well-being of this group of participants could be established. Almost one
      third of the respondents claimed to follow a healthier lifestyle as a result of
      the screening. There are, however, also indications for a certain 'certificate of
      health effect': about half of the smokers and the physically inactive considered
      that the favourable screening results legitimated their unhealthy lifestyle. An
      unfavourable screening result led to additional medical consumption in almost
      half of the respondents. The respondents appreciated the screening and especially
      the less educated had a very positive attitude towards early diagnosis in
      general. CONCLUSIONS: Those screened positive showed no diminished well-being;
      their health behaviour improved because of the screening and their medical
      consumption increased. Many of those screened negative considered the test result
      a reason to continue their unhealthy lifestyle.

PMID- 22388486
TI  - Informed consent by cancer patients in Japanese case law.

PMID- 22388487
TI  - Title unavailable.

PMID- 22388488
TI  - Treating colon cancer with a suicide gene delivered by self-assembled cationic
      MPEG-PCL micelles.
AB  - Biodegradable cationic micelles show promise for applications in gene delivery.
      In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)
      poly(epsilon-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel
      cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles
      had a mean particle size of 46 +/- 5.6 nm and a zeta potential of 41.8 +/- 0.5
      mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard),
      DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover,
      we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat
      colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce
      apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon
      cancer cells in vitro. An in vivo study indicated that intraperitoneal
      administration of DMP micelles delivered the Survivin-T34A gene and efficiently
      inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant
      ascites. These data suggest that DMP may be a novel gene carrier, and its
      delivery of the S-T34A gene may have promising applications in the treatment of
      colon cancer.

PMID- 22388489
TI  - Loss of Cellulose synthase-like F6 function affects mixed-linkage glucan
      deposition, cell wall mechanical properties, and defense responses in vegetative
      tissues of rice.
AB  - Mixed-linkage glucan (MLG) is a cell wall polysaccharide containing a backbone of
      unbranched (1,3)- and (1,4)-linked beta-glucosyl residues. Based on its
      occurrence in plants and chemical characteristics, MLG has primarily been
      associated with the regulation of cell wall expansion due to its high and
      transient accumulation in young, expanding tissues. The Cellulose synthase-like F
      (CslF) subfamily of glycosyltransferases has previously been implicated in
      mediating the biosynthesis of this polymer. We confirmed that the rice (Oryza
      sativa) CslF6 gene mediates the biosynthesis of MLG by overexpressing it in
      Nicotiana benthamiana. Rice cslf6 knockout mutants show a slight decrease in
      height and stem diameter but otherwise grew normally during vegetative
      development. However, cslf6 mutants display a drastic decrease in MLG content
      (97% reduction in coleoptiles and virtually undetectable in other tissues).
      Immunodetection with an anti-MLG monoclonal antibody revealed that the
      coleoptiles and leaves retain trace amounts of MLG only in specific cell types
      such as sclerenchyma fibers. These results correlate with the absence of
      endogenous MLG synthase activity in mutant seedlings and 4-week-old sheaths.
      Mutant cell walls are weaker in mature stems but not seedlings, and more brittle
      in both stems and seedlings, compared to wild type. Mutants also display lesion
      mimic phenotypes in leaves, which correlates with enhanced defense-related gene
      expression and enhanced disease resistance. Taken together, our results underline
      a weaker role of MLG in cell expansion than previously thought, and highlight a
      structural role for MLG in nonexpanding, mature stem tissues in rice.

PMID- 22388491
TI  - Caffeine and sprinting performance:  dose responses and efficacy.
AB  - The aims of this study were to evaluate the effects of caffeine supplementation
      on sprint cycling performance and to determine if there was a dose-response
      effect. Using a randomized, double-blind, placebo-controlled design, 17 well
      trained men (age: 24 +/- 6 years, height: 1.82 +/- 0.06 m, and body mass(bm):
      82.2 +/- 6.9 kg) completed 7 maximal 10-second sprint trials on an
      electromagnetically braked cycle ergometer. Apart from trial 1 (familiarization),
      all the trials involved subjects ingesting a gelatine capsule containing either
      caffeine or placebo (maltodextrin) 1 hour before each sprint. To examine dose
      response effects, caffeine doses of 2, 4, 6, 8, and 10 mg.kg bm(-1) were used.
      There were no significant (p >= 0.05) differences in baseline measures of plasma
      caffeine concentration before each trial (grand mean: 0.14 +/- 0.28 MUg.ml(-1)).
      There was, however, a significant supplement * time interaction (p < 0.001), with
      larger caffeine doses producing higher postsupplementation plasma caffeine
      levels. In comparison with placebo, caffeine had no significant effect on peak
      power (p = 0.11), mean power (p = 0.55), or time to peak power (p = 0.17). There
      was also no significant effect of supplementation on pretrial blood lactate (p =
      0.58), but there was a significant time effect (p = 0.001), with blood lactate
      reducing over the 50 minute postsupplementation rest period from 1.29 +/- 0.36 to
      1.06 +/- 0.33 mmol.L(-1). The results of this study show that caffeine
      supplementation has no effect on short-duration sprint cycling performance,
      irrespective of the dosage used.

PMID- 22388490
TI  - Synergistic biosynthesis of biphasic ethylene and reactive oxygen species in
      response to hemibiotrophic Phytophthora parasitica in tobacco plants.
AB  - We observed the biphasic production of ethylene and reactive oxygen species (ROS)
      in susceptible tobacco (Nicotiana tabacum 'Wisconsin 38') plants after shoot
      inoculation with Phytophthora parasitica var nicotianae. The initial transient
      increase in ROS and ethylene at 1 and 3 h (phase I), respectively, was followed
      by a second massive increase at 48 and 72 h (phase II), respectively, after
      pathogen inoculation. This biphasic pattern of ROS production significantly
      differed from the hypersensitive response exhibited by cryptogein-treated wild
      type tobacco plants. The biphasic increase in ROS production was mediated by both
      NADPH oxidase isoforms, respiratory burst oxidase homolog (Rboh) D and RbohF.
      Conversely, different 1-aminocyclopropane-1-carboxylic acid synthase members were
      involved in specific phases of ethylene production: NtACS4 in the first phase and
      NtACS1 in the second phase. Biphasic production of ROS was inhibited in
      transgenic antisense plant lines expressing 1-aminocyclopropane-1-carboxylic acid
      synthase/oxidase or ethylene-insensitive3 as well as in transgenic plants
      impaired in ROS production. All tested transgenic plants were more tolerant
      against P. parasitica var nicotianae infection as determined based on trypan blue
      staining and pathogen proliferation. Further, silencing of NtACS4 blocked the
      second massive increase in ROS production as well as pathogen progression.
      Pathogen tolerance was due to the inhibition of ROS and ethylene production,
      which further resulted in lower activation of ROS-detoxifying enzymes.
      Accordingly, the synergistic inhibition of the second phase of ROS and ethylene
      production had protective effects against pathogen-induced cell damage. We
      conclude that the levels of ethylene and ROS correlate with compatible P.
      parasitica proliferation in susceptible plants.

PMID- 22388492
TI  - The normalization of explosive functional movements in a diverse population of
      elite American football players.
AB  - The objective of this study was to investigate the need to normalize, for body
      mass, explosive functional tasks in a population exhibiting diverse body masses.
      Measures investigated in elite college American football players attending the
      National Football League's annual combine (n = 1,136) were the 9.1-, 18.3-, and
      36.6-m sprints, vertical and horizontal jumps, 18.3-m shuttle, and 3-cone drill.
      To determine the relationship between body mass and performance outcomes,
      Pearson's correlation coefficients (r) were generated using log-transformed data.
      Task-specific allometric exponents, accounting for body mass, were also
      determined. The strength of the correlations suggests that sprint and jump
      abilities are associated with body mass, whereas change-of-direction ability is
      not. The determined allometric exponents range between 0.296 and -0.463 for the
      sprint and jump tasks and are -0.022 and -0.006 for the 18.3-m shuttle and the 3
      cone drill, respectively. In populations exhibiting relatively large variations
      in body mass, normalization of sprint and jump abilities is recommended, whereas
      normalization of change-of-direction ability is unwarranted. Novel suggestions
      derived from the present research are that sprint and jump abilities in diverse
      populations warrant normalization and that physical attributes associated with
      explosive functional movements deserve attribute-specific consideration when
      contemplating normalization.

PMID- 22388493
TI  - Photolability of NO in designed metal nitrosyls with carboxamido-N donors: a
      theoretical attempt to unravel the mechanism.
AB  - During the past few years, photoactive metal nitrosyls (NO complexes of metals)
      have drawn attention as potential drugs for delivery of nitric oxide (NO) to
      biological targets under the control of light. Major success in this area has
      been achieved with designed metal nitrosyls derived from ligands that contain
      carboxamide group(s). A number of iron, manganese and ruthenium {MNO}(6)
      nitrosyls of such kind exhibit excellent NO photolability under low-power visible
      and near-IR light. The results of theoretical studies on these NO-donors have
      provided insight into (a) the electronic transitions that lead to photorelease of
      NO and (b) the structural features of the ligands that dictate the sensitivity of
      the nitrosyls to light of specific wavelengths. In addition, the results have
      afforded clear understanding of the electronic configurations of the various
      nitrosyls. This article highlights these results in a coherent manner. Good
      matches between the predicted and observed spectral features and NO photolability
      strongly suggest that theoretical studies should be an integral part of the smart
      design of such NO-donors in the future research.

PMID- 22388494
TI  - Research to support universal coverage reforms in Africa: the SHIELD project.

PMID- 22388495
TI  - Modelling the affordability and distributional implications of future health care
      financing options in South Africa.
AB  - South Africa is considering introducing a universal health care system. A key
      concern for policy-makers and the general public is whether or not this reform is
      affordable. Modelling the resource and revenue generation requirements of
      alternative reform options is critical to inform decision-making. This paper
      considers three reform scenarios: universal coverage funded by increased
      allocations to health from general tax and additional dedicated taxes; an
      alternative reform option of extending private health insurance coverage to all
      formal sector workers and their dependents with the remainder using tax-funded
      services; and maintaining the status quo. Each scenario was modelled over a 15
      year period using a spreadsheet model. Statistical analyses were also undertaken
      to evaluate the impact of options on the distribution of health care financing
      burden and benefits from using health services across socio-economic groups.
      Universal coverage would result in total health care spending levels equivalent
      to 8.6% of gross domestic product (GDP), which is comparable to current spending
      levels. It is lower than the status quo option (9.5% of GDP) and far lower than
      the option of expanding private insurance cover (over 13% of GDP). However,
      public funding of health services would have to increase substantially. Despite
      this, universal coverage would result in the most progressive financing system if
      the additional public funding requirements are generated through a surcharge on
      taxable income (but not if VAT is increased). The extended private insurance
      scheme option would be the least progressive and would impose a very high payment
      burden; total health care payments on average would be 10.7% of household
      consumption expenditure compared with the universal coverage (6.7%) and status
      quo (7.5%) options. The least pro-rich distribution of service benefits would be
      achieved under universal coverage. Universal coverage is affordable and would
      promote health system equity, but needs careful design to ensure its long-term
      sustainability.

PMID- 22388496
TI  - Progressivity of health care financing and incidence of service benefits in
      Ghana.
AB  - The National Health Insurance (NHI) scheme was introduced in Ghana in 2004 as a
      pro-poor financing strategy aimed at removing financial barriers to health care
      and protecting all citizens from catastrophic health expenditures, which
      currently arise due to user fees and other direct payments. A comprehensive
      assessment of the financing and benefit incidence of health services in Ghana was
      undertaken. These analyses drew on secondary data from the Ghana Living Standards
      Survey (2005/2006) and from an additional household survey which collected data
      in 2008 in six districts covering the three main ecological zones of Ghana.
      Findings show that Ghana's health care financing system is progressive, driven
      largely by the progressivity of taxes. The national health insurance levy (which
      is part of VAT) is mildly progressive while NHI contributions by the informal
      sector are regressive. The distribution of total benefits from both public and
      private health services is pro-rich. However, public sector district-level
      hospital inpatient care is pro-poor and benefits of primary-level health care
      services are relatively evenly distributed. For Ghana to attain an equitable
      health system and fully achieve universal coverage, it must ensure that the poor,
      most of whom are not currently covered by the NHI, are financially protected, and
      it must address the many access barriers to health care.

PMID- 22388497
TI  - Who pays and who benefits from health care? An assessment of equity in health
      care financing and benefit distribution in Tanzania.
AB  - Little is known about health system equity in Tanzania, whether in terms of
      distribution of the health care financing burden or distribution of health care
      benefits. This study undertook a combined analysis of both financing and benefit
      incidence to explore the distribution of health care benefits and financing
      burden across socio-economic groups. A system-wide analysis of benefits was
      undertaken, including benefits from all providers irrespective of ownership. The
      analysis used the household budget survey (HBS) from 2001, the most recent
      nationally representative survey data publicly available at the time, to analyse
      the distribution of health care payments through user fees, health insurance
      contributions [from the National Health Insurance Fund (NHIF) for the formal
      sector and the Community Health Fund (CHF), for the rural informal sector] and
      taxation. Due to lack of information on NHIF and CHF contributions in the HBS, a
      primary survey was administered to estimate CHF enrollment and contributions;
      assumptions were used to estimate NHIF contributions within the HBS. Data from
      the same household survey, administered to 2224 households in seven
      districts/councils, was used to analyse the distribution of health care benefits
      across socio-economic groups. The health financing system was mildly progressive
      overall, with income taxes and NHIF contributions being the most progressive
      financing sources. Out-of-pocket payments and contributions to the CHF were
      regressive. The health benefit distribution was fairly even but the poorest
      received a lower share of benefits relative to their share of need for health
      care. Public primary care facility use was pro-poor, whereas higher level and
      higher cost facility use was generally pro-rich. We conclude that health
      financing reforms can improve equity, so long as integration of health insurance
      schemes is promoted along with cross-subsidization and greater reliance on
      general taxation to finance health care for the poorest.

PMID- 22388498
TI  - Paying for and receiving benefits from health services in South Africa: is the
      health system equitable?
AB  - There is a global challenge for health systems to ensure equity in both the
      delivery and financing of health care. However, many African countries still do
      not have equitable health systems. Traditionally, equity in the delivery and the
      financing of health care are assessed separately, in what may be termed 'partial'
      analyses. The current debate on countries moving toward universal health systems,
      however, requires a holistic understanding of equity in both the delivery and the
      financing of health care. The number of studies combining these aspects to date
      is limited, especially in Africa. An assessment of overall health system equity
      involves assessing health care financing in relation to the principles of
      contributing to financing according to ability to pay and benefiting from health
      services according to need for care. Currently South Africa is considering major
      health systems restructuring toward a universal system. This paper examines
      together, for both the public and the private sectors, equity in the delivery and
      financing of health care in South Africa. Using nationally representative
      datasets and standard methodologies for assessing progressivity in health care
      financing and benefit incidence, this paper reports an overall progressive
      financing system but a pro-rich distribution of health care benefits. The
      progressive financing system is driven mainly by progressive private medical
      schemes that cover a small portion of the population, mainly the rich. The
      distribution of health care benefits is not only pro-rich, but also not in line
      with the need for health care; richer groups receive a far greater share of
      service benefits within both public and private sectors despite having a
      relatively lower share of the ill-health burden. The importance of the findings
      for the design of a universal health system is discussed.

PMID- 22388499
TI  - Progress towards universal coverage: the health systems of Ghana, South Africa
      and Tanzania.
AB  - A desire to enhance protection against health care costs and improve equity of
      access to health care lies at the core of many health sector financing
      initiatives. Until recently, international debates about financing and health
      equity have focused primarily on mechanisms to promote equity in relation to very
      specific elements of health systems. However, in recent years there has been
      growing interest in considering these equity challenges from a more systemic
      perspective. In this context, universal health coverage is becoming a rallying
      call, with a focus on how best universal coverage can be financed. This paper is
      the first in a special issue which presents a body of research whose overall aim
      was to critically evaluate existing inequities in health care financing and
      provision in Ghana, South Africa and Tanzania, and the extent to which health
      insurance mechanisms (broadly defined) could address financial protection and
      equity of access challenges. In this first paper we introduce the countries'
      health systems, with a special emphasis on existing mechanisms for financial
      protection. We also identify in broad terms the key challenges for universal
      coverage, setting the scene for the subsequent papers.

PMID- 22388500
TI  - Factors influencing the burden of health care financing and the distribution of
      health care benefits in Ghana, Tanzania and South Africa.
AB  - In Ghana, Tanzania and South Africa, health care financing is progressive
      overall. However, out-of-pocket payments and health insurance for the informal
      sector are regressive. The distribution of health care benefits is generally pro
      rich. This paper explores the factors influencing these distributions in the
      three countries. Qualitative data were collected through focus group discussions
      and in-depth interviews with insurance scheme members, the uninsured, health care
      providers and managers. Household surveys were also conducted in all countries.
      Flat-rate contributions contributed to the regressivity of informal sector
      voluntary schemes, either by design (in Tanzania) or due to difficulties in
      identifying household income levels (in Ghana). In all three countries, the
      regressivity of out-of-pocket payments is due to the incomplete enforcement of
      exemption and waiver policies, partial or no insurance cover among poorer
      segments of the population and limited understanding of entitlements among these
      groups. Generally, the pro-rich distribution of benefits is due to limited access
      to higher level facilities among poor and rural populations, who rely on public
      primary care facilities and private pharmacies. Barriers to accessing health care
      include medical and transport costs, exacerbated by the lack of comprehensive
      insurance coverage among poorer groups. Service availability problems, including
      frequent drug stock-outs, limited or no diagnostic equipment, unpredictable
      opening hours and insufficient skilled staff also limit service access. Poor
      staff attitudes and lack of confidence in the skills of health workers were found
      to be important barriers to access. Financing reforms should therefore not only
      consider how to generate funds for health care, but also explicitly address the
      full range of affordability, availability and acceptability barriers to access in
      order to achieve equitable financing and benefit incidence patterns.

PMID- 22388501
TI  - Social solidarity and willingness to tolerate risk- and income-related cross
      subsidies within health insurance: experiences from Ghana, Tanzania and South
      Africa.
AB  - The importance of ill-health in perpetuating poverty is well recognized. In order
      to prevent the damaging downward spiral of poverty and illness, there is a need
      for a greater level of social protection, with greater cross-subsidization
      between the poor and wealthy, and the healthy and those with ill-health.  The aim
      of this paper is to examine individual preferences for willingness to pre-pay for
      health care and willingness to cross-subsidize the sick and the poor in Ghana,
      South Africa and Tanzania. Household surveys in the three countries elicited
      views on cross-subsidization within health care financing. The paper examines how
      these preferences varied by socio-economic status, other respondent
      characteristics, and the extent and type of experience of health insurance in the
      light of country context.  In South Africa and Ghana, 62% and 55% of total
      respondents, respectively, were in favour of a progressive financing system in
      which richer groups would pay a higher proportion of income than poorer groups,
      rather than a system where individuals pay the same proportion of income
      irrespective of their wealth (proportional). In Tanzania, 45% of the total sample
      were willing to pay for the health care of the poor. However, in all three
      countries, a progressive system was favoured by a smaller proportion of the most
      well off than of less well off groups.  Solidarity has been considered to be a
      collective property of a specific socio-political culture, based on shared
      expectations and developed as part of a communal, historical learning process.
      The three countries had different experiences of health insurance and this may
      have contributed to the above differences in expressed willingness to pay between
      countries. Building and 'living with' institutions that provide affordable
      universal coverage is likely to be an essential part of the learning process
      which supports the development of social solidarity.

PMID- 22388502
TI  - Using stakeholder analysis to support moves towards universal coverage: lessons
      from the SHIELD project.
AB  - Stakeholder analysis is widely recommended as a tool for gathering insights on
      policy actor interests in, positions on, and power to influence, health policy
      issues. Such information is recognized to be critical in developing viable health
      policy proposals, and is particularly important for new health care financing
      proposals that aim to secure universal coverage (UC). However, there remain
      surprisingly few published accounts of the use of stakeholder analysis in health
      policy development generally, and health financing specifically, and even fewer
      that draw lessons from experience about how to do and how to use such analysis.
      This paper, therefore, aims to support those developing or researching UC reforms
      to think both about how to conduct stakeholder analysis, and how to use it to
      support evidence-informed pro-poor health policy development. It presents
      practical lessons and ideas drawn from experience of doing stakeholder analysis
      around UC reforms in South Africa and Tanzania, combined with insights from other
      relevant material. The paper has two parts. The first presents lessons of
      experience for conducting a stakeholder analysis, and the second, ideas about how
      to use the analysis to support policy design and the development of actor and
      broader political management strategies. Comparison of experience across South
      Africa and Tanzania shows that there are some commonalities concerning which
      stakeholders have general interests in UC reform. However, differences in context
      and in reform proposals generate differences in the particular interests of
      stakeholders and their likely positioning on reform proposals, as well as in
      their relative balance of power. It is, therefore, difficult to draw cross
      national policy comparisons around these specific issues. Nonetheless, the paper
      shows that cross-national policy learning is possible around the approach to
      analysis, the factors influencing judgements and the implications for, and
      possible approaches to, management of policy processes. Such learning does not
      entail generalization about which UC reform package offers most gain in any
      setting, but rather about how to manage the reform process within a particular
      context.

PMID- 22388503
TI  - Inside the black box: modelling health care financing reform in data-poor
      contexts.
AB  - Modelling the likely financial resource requirements and potential sources of
      revenue for health system reform options is of great potential value to policy
      makers. Models provide an indication of the financial feasibility and
      sustainability of such reforms and highlight the implications of alternative
      reform paths. There has been increasing use of financial models of health sector
      reform in recent years, particularly since the development of user-friendly
      software such as SimIns, which was developed by the World Health Organization
      (WHO) and Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ). This paper
      outlines the process of developing country-specific spreadsheet-based models to
      explore the financial resource requirements of health system reform options in
      South Africa and Tanzania. Building one's own model, although time consuming,
      allows for greater flexibility and forces the analysts to give careful
      consideration to the assumptions underlying the model. The core variables in our
      models are: population, health service utilization rates and unit costs. The
      paper outlines the types of disaggregation of these variables, the range of
      possible data sources, key challenges with securing accurate data for each
      variable, and relevant evidence on which to base key assumptions, and how we went
      about addressing these challenges. We also briefly review how to model the
      revenue-generating potential of alternative sources of health care financing. The
      intention of the paper is to provide guidance for analysts who wish to develop
      their own models, and to illustrate, with reference to the South African and
      Tanzanian modelling experience, how one has to adapt to data constraints and
      context-specific modelling requirements.

PMID- 22388505
TI  - Computerised tomography performance.

PMID- 22388504
TI  - Modelling the implications of moving towards universal coverage in Tanzania.
AB  - A model was developed to assess the impact of possible moves towards universal
      coverage in Tanzania over a 15-year time frame. Three scenarios were considered:
      maintaining the current situation ('the status quo'); expanded health insurance
      coverage (the estimated maximum achievable coverage in the absence of premium
      subsidies, coverage restricted to those who can pay); universal coverage to all
      (government revenues used to pay the premiums for the poor). The model estimated
      the costs of delivering public health services and all health services to the
      population as a proportion of Gross Domestic Product (GDP), and forecast revenue
      from user fees and insurance premiums. Under the status quo, financial protection
      is provided to 10% of the population through health insurance schemes, with the
      remaining population benefiting from subsidized user charges in public
      facilities. Seventy-six per cent of the population would benefit from financial
      protection through health insurance under the expanded coverage scenario, and
      100% of the population would receive such protection through a mix of insurance
      cover and government funding under the universal coverage scenario. The expanded
      and universal coverage scenarios have a significant effect on utilization levels,
      especially for public outpatient care. Universal coverage would require an
      initial doubling in the proportion of GDP going to the public health system.
      Government health expenditure would increase to 18% of total government
      expenditure. The results are sensitive to the cost of health system
      strengthening, the level of real GDP growth, provider reimbursement rates and
      administrative costs. Promoting greater cross-subsidization between insurance
      schemes would provide sufficient resources to finance universal coverage.
      Alternately, greater tax funding for health could be generated through an
      increase in the rate of Value-Added Tax (VAT) or expanding the income tax base.
      The feasibility and sustainability of efforts to promote universal coverage will
      depend on the ability of the system to contain costs.

PMID- 22388506
TI  - Hard X-ray emission from high intensity short laser pulse produced Al, Mo and Ta
      plasmas.
AB  - K-edge and Ross filters techniques were used to measure quantitatively the X-ray
      emission from laser heated Al, Mo, and Ta plasmas in the range of 10 to 100 keV.
      The INRS Table Top Terawatt laser system using Chirped Pulse Amplification
      technique supplied a focused laser pulse of about 300 mJ in 450 fs duration at
      lambda = 0.53 MUm, achieving irradiation intensities on the target surface up to
      5 * 1017 W/cm2. The experimental results are compared to calculation of the hard
      X-ray radiation based on bombardment of solid target by electrons. Furthermore,
      the dependence of X-ray emission on laser energy, irradiation intensity and the
      target atomic number are discussed.

PMID- 22388507
TI  - Grazing incidence synchrotron X-ray topography as a tool for denuded zone studies
      of silicon wafers.
AB  - Reflection topographs of annealed Czochralski-grown silicon wafers are made with
      synchrotron white beam radiation at grazing angles of 0.2 degree to 3 degree.
      Information on the uniformity of the denuded zone is obtained from a number of
      grazing incidence topographs, which according to calculations turn out to be
      almost completely monochromatic having a negligible harmonic content. The
      calculated penetration depth ranges from 1 to 100 um depending on the grazing
      angle and reflection used. The grazing incidence topographs are compared with
      section topographs of the same samples.

PMID- 22388508
TI  - X-UV lamellar multilayer amplitude gratings.
AB  - The concept of X-UV Lamellar Multilayer Amplitude Grating (LMAG) is introduced
      and a method of fabrication is given. Dynamical and kinematic theories of the
      diffraction by a LMAG are presented. Different applications of the LMAGs are
      considered. The first one is the achievement of a narrow bandpass multilayer
      monochromator for the X-UV domain. The second one is the reduction of specular
      background in the reflectivity curve of a multilayer structure. The third one is
      the polychromator system which allows one to split spatially and to perform a
      spectral sampling of a polychromatic beam. Finally we studied experimentally the
      behavior of an LMAG in conical mounting.

PMID- 22388509
TI  - Additional confirmation of action constant for bremsstrahlung from electron-and
      nucleus collisions.
AB  - A new action constant for bremsstrahlung has been derived and published by the
      author (Journal of X-Ray Science and Technology 6, 1996, 261). Experimental
      confirmation of that action constant by measurements of the intensity of
      bremsstrahlung produced by electron beams on pure metal targets, has also been
      published by the author (Journal of X-Ray Science and Technology 7, 1997, 327
      330). From the data in the second paper, additional experimental evidence is
      obtained for this paper by overcoming the limitations associated with
      normalization of the number of atoms per unit volume. The dependence of the
      intensity on the exponent of the atomic number, Z, of the target elements is
      measured to be 1.32, with a standard deviation of plus or minus 0.05, in close
      agreement with the predicted value of 4/3.

PMID- 22388510
TI  - Optimum collimator for proximity X-ray lithography - Theoretical analysis.
AB  - The paper deals with the application of soft X-ray optics to the enhancement of
      the efficiency of X-ray proximity lithography based on a point X-ray source. The
      grazing incidence X-ray collimators are shown to increase the efficiency
      coefficient in several hundreds times. The design of the optimum X-ray collimator
      is proposed and analysed for the scheme of X-ray proximity lithography with
      spatial resolution 0.05 um. The collimator transforms the divergent radiation of
      an X-ray point source into high collimated beam that illuminates uniformly the
      mask at normal incidence.

PMID- 22388511
TI  - The function and regulatory network of WhiB and WhiB-like protein from
      comparative genomics and systems biology perspectives.
AB  - whi genes, named after the mutations turning Streptomyces coelicolor colonies
      into white, exist largely in Actinomyces and Mycobacterium. whiB genes, a
      subclass of whi, involve in wide range of events, such as cell division, spore
      formation, nutrient starvation, pathogenesis, antibiotic resistance, and stress
      sense. To better understand the role of this family in physiology and pathology
      in the important pathogen-Mycobacterium tuberculosis, WhiB and WhiB-like proteins
      function and structures of were bioinformatically dissected. Seven WhiB proteins
      can be found in M. tuberculosis genome, most are highly conserved. Based on the
      data mining of published microarray profiling of wild type and mutants
      transcriptome response to diverse treatments, a regulatory network of whiB is
      established. Some findings from this network are obvious. WhiB2 and WhiB7 might
      be key nodes in drug resistance, WhiB3 might involve in the maintenance of redox
      homeostasis. These works provide new Mycobacterium persistence and virulence
      hypothesis for future experimental validation.

PMID- 22388513
TI  - Left ventricular aneurysm, aortic stenosis, and arcade mitral valve: coexistence
      of three rare congenital heart defects.
AB  - This report presents two fetuses with three rare congenital heart defects:
      congenital ventricular aneurysm, arcade mitral valve, and unicommissural aortic
      valve. Because interaction between the endocardium and the myocardium is
      essential for development of the myocardium and heart valves, the authors
      hypothesized that these three defects could be related to abnormal signaling
      between the endocardium and the myocardium during critical phases of cardiac
      development. This combination of defects might be incompatible with fetal
      survival to term.

PMID- 22388514
TI  - Copula identifiability conditions for dependent truncated data model.
AB  - We provide a copula identifiability condition for dependent truncated data model.
      The identifiability is characterized by the strong lower-left tail
      identifiability of the copula family. We show that the commonly used Archimedean
      copula families with analytic generator functions satisfy this condition.

PMID- 22388515
TI  - Molecular pathways: fibroblast growth factor signaling: a new therapeutic
      opportunity in cancer.
AB  - The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR)
      signaling axis plays an important role in normal organ, vascular, and skeletal
      development. Deregulation of FGFR signaling through genetic modification or
      overexpression of the receptors (or their ligands) has been observed in numerous
      tumor settings, whereas the FGF/FGFR axis also plays a key role in driving tumor
      angiogenesis. A growing body of preclinical data shows that inhibition of FGFR
      signaling can result in antiproliferative and/or proapoptotic effects, both in
      vitro and in vivo, thus confirming the validity of the FGF/FGFR axis as a
      potential therapeutic target. In the past, development of therapeutic approaches
      to target this axis has been hampered by our inability to develop FGFR-selective
      agents. With the advent of a number of new modalities for selectively inhibiting
      FGF/FGFR signaling, we are now in a unique position to test and validate
      clinically the many hypotheses that have been generated preclinically.

PMID- 22388517
TI  - A GAIN in understanding autoproteolytic G protein-coupled receptors and
      polycystic kidney disease proteins.

PMID- 22388524
TI  - Assessing the costs of second-generation antipsychotics.

PMID- 22388519
TI  - Structural insights into initial and intermediate steps of the ribosome-recycling
      process.
AB  - The ribosome-recycling factor (RRF) and elongation factor-G (EF-G) disassemble
      the 70S post-termination complex (PoTC) into mRNA, tRNA, and two ribosomal
      subunits. We have determined cryo-electron microscopic structures of the PoTC.RRF
      complex, with and without EF-G. We find that domain II of RRF initially interacts
      with universally conserved residues of the 23S rRNA helices 43 and 95, and
      protein L11 within the 50S ribosomal subunit. Upon EF-G binding, both RRF and
      tRNA are driven towards the tRNA-exit (E) site, with a large rotational movement
      of domain II of RRF towards the 30S ribosomal subunit. During this intermediate
      step of the recycling process, domain II of RRF and domain IV of EF-G adopt
      hitherto unknown conformations. Furthermore, binding of EF-G to the PoTC.RRF
      complex reverts the ribosome from ratcheted to unratcheted state. These results
      suggest that (i) the ribosomal intersubunit reorganizations upon RRF binding and
      subsequent EF-G binding could be instrumental in destabilizing the PoTC and (ii)
      the modes of action of EF-G during tRNA translocation and ribosome-recycling
      steps are markedly different.

PMID- 22388526
TI  - Economic grand rounds: economic costs of failure to monitor adverse effects of
      second-generation antipsychotics: an underestimated factor.
AB  - Since 2003, the U.S. Food and Drug Administration as well as the American
      Diabetes Association, the American Psychiatric Association, and others have
      called for routine monitoring of cardiometabolic risk factors for patients of all
      ages prescribed second-generation antipsychotic medications. This survey of major
      public and private mental health treatment systems in 2010 found that adherence
      to such guidelines was limited. The authors describe some of the impediments to
      widespread monitoring of cardiometabolic risk factors among psychiatric patients
      taking second-generation antipsychotics and advocate for a nationwide commitment
      to providing the organizational and financial supports necessary to ensure
      systematic screening of cardiometabolic health among such patients.

PMID- 22388518
TI  - Multiple factors dictate target selection by Hfq-binding small RNAs.
AB  - Hfq-binding small RNAs (sRNAs) in bacteria modulate the stability and
      translational efficiency of target mRNAs through limited base-pairing
      interactions. While these sRNAs are known to regulate numerous mRNAs as part of
      stress responses, what distinguishes targets and non-targets among the mRNAs
      predicted to base pair with Hfq-binding sRNAs is poorly understood. Using the Hfq
      binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions
      using only the three unstructured regions of Spot 42 substantially improved the
      identification of previously known and novel Spot 42 targets. Furthermore,
      increasing the extent of base-pairing in single or multiple base-pairing regions
      improved the strength of regulation, but only for the unstructured regions of
      Spot 42. We also found that non-targets predicted to base pair with Spot 42
      lacked an Hfq-binding site, folded into a secondary structure that occluded the
      Spot 42 targeting site, or had overlapping Hfq-binding and targeting sites. By
      modifying these features, we could impart Spot 42 regulation on non-target mRNAs.
      Our results thus provide valuable insights into the requirements for target
      selection by sRNAs.

PMID- 22388527
TI  - Public-academic partnerships: evidence-based implementation: the role of
      sustained community-based practice and research partnerships.
AB  - This column describes a process for adapting an evidence-based practice in
      community clinics in which researchers and community providers participated and
      the resulting framework for implementation of the practice-Replicating Effective
      Programs-Facilitation. A two-day meeting for the Recovery-Oriented Collaborative
      Care study was conducted to elicit input from more than 50 stakeholders,
      including community providers, health care administrators, and implementation
      researchers. The process illustrates an effective researcher-community
      partnership in which stakeholders worked together not only to adapt the evidence
      based practice to the needs of the clinical settings but also to develop the
      implementation strategy.

PMID- 22388528
TI  - Does assertive community outreach improve social support? Results from the
      Lambeth Study of early-episode psychosis.
AB  - OBJECTIVES: Specialized early intervention by a team providing assertive
      community treatment (ACT) is beneficial to the recovery, housing, and employment
      of individuals with schizophrenia, but few studies have examined its effect on
      social support. This study assessed whether the ACT model of care was related to
      clinical and social outcomes among patients who had experienced a first episode
      of psychosis. METHODS: The sample was drawn from the Lambeth Early Onset Trial, a
      study of 144 patients in the United Kingdom who sought treatment for a first
      episode of psychosis between January 2000 and October 2001 and who were randomly
      assigned to a specialized early intervention modeled on ACT or standard care. The
      Positive and Negative Syndrome Scale, the Global Assessment of Functioning, and
      the Significant Others Scale were administered at six-month and 18-month follow
      ups. RESULTS: Data on social support were available at both follow-ups for 57
      patients assigned to specialized care and 50 patients assigned to standard care.
      The two groups were similar in personal characteristics, relationship status, and
      living arrangements at baseline and at six-month follow-up, but by 18 months,
      patients in specialized care reported having a higher mean+/-SD number of
      significant others in their social networks than did standard care patients
      (2.40+/-1.20 and 1.71+/-1.06, respectively; p=.01). They also achieved superior
      clinical outcomes at 18 months, and these outcomes were associated with network
      size. CONCLUSION: Early intervention by using an ACT model of care may improve
      clinical results by reestablishing or maintaining bonds between patients and
      family, friends, and acquaintances.

PMID- 22388530
TI  - Depression screening of perinatal women by the Des Moines Healthy Start Project:
      program description and evaluation.
AB  - OBJECTIVE: Maternal depression is linked to poor infant and child outcome. In
      2001, the U.S. Health Resources and Services Administration required all Healthy
      Start programs to incorporate maternal-depression screening as part of home
      visiting services. This article describes the implementation and results of
      depression screening by the Des Moines Healthy Start Project between 2002 and
      2009. The study represents the first longitudinal assessment of the Healthy Start
      maternal-depression screening initiative. METHODS: The evaluation assessed staff
      compliance with a protocol for screening for depression among clients at regular
      intervals during the prenatal and postnatal periods until the client's child was
      two years old. Rates of acceptance of referral for treatment and treatment
      seeking as well as depression outcomes were measured. RESULTS: A total of 1,902
      women were served by the Des Moines Healthy Start Project between 2002 and 2009.
      Compliance with the screening protocol was immediately high and increased
      significantly over the evaluation period, from 83% in 2002 to 98% in 2009. Of the
      573 women who had elevated depression scores but who were not already in
      treatment, 64% accepted a referral, and 47% reported receiving treatment.
      Predictors of referral acceptance and treatment included higher depression scores
      and speaking English as a primary language. Depression severity significantly
      decreased for women who reported receiving treatment. CONCLUSIONS: A federal
      screening initiative identified a significant number of women who were at risk
      for maternal depression and connected them with treatment resources. Continuing
      work should assess the impact of this initiative on outcomes of women and
      children.

PMID- 22388529
TI  - Church-based health programs for mental disorders among African Americans: a
      review.
AB  - OBJECTIVE: African Americans underutilize traditional mental health services,
      compared with white Americans. The authors conducted a systematic review of
      studies involving church-based health promotion programs for mental disorders
      among African Americans to assess the feasibility of utilizing such programs to
      address racial disparities in mental health care. METHODS: A literature review of
      MEDLINE, PsycINFO, CINAHL, and ATLA Religion databases was conducted to identify
      articles published between January 1, 1980, and December 31, 2009. Inclusion
      criteria were as follows: studies were conducted in a church; the primary
      objective involved assessment, perceptions and attitudes, education, prevention,
      group support, or treatment for DSM-IV mental disorders or their correlates;
      number of participants was reported; qualitative or quantitative data were
      reported; and African Americans were the target population. RESULTS: Of 1,451
      studies identified, only eight met inclusion criteria. Five studies focused on
      substance-related disorders, six were designed to assess the effects of a
      specific intervention, and six targeted adults. One study focused on depression
      and was limited by a small sample size of seven participants. CONCLUSIONS:
      Although church-based health promotion programs have been successful in
      addressing racial disparities for several chronic medical conditions, the
      literature on such programs for mental disorders is extremely limited. More
      intensive research is needed to establish the feasibility and acceptability of
      utilizing church-based health promotion programs as a possible resource for
      screening and treatment to improve disparities in mental health care for African
      Americans.

PMID- 22388531
TI  - Psychiatric symptoms and alcohol use in community violence by persons with a
      psychotic disorder or depression.
AB  - OBJECTIVE: Prior studies have shown a significant but modest association between
      mental disorders and violence and an increased risk in the presence of co
      occurring substance use disorders. Categorical diagnoses, however, have limited
      utility when assessing dynamic risk state over time. This study used data from
      the MacArthur Violence Risk Assessment Study to examine the relationship of
      symptom levels and alcohol use to violence in repeated observations within two
      diagnostic groups. METHODS: Participants with a primary categorical diagnosis of
      depression (N=386) or a psychotic disorder (N=201) were identified. Subscale
      scores for affective or positive symptoms from the Brief Psychiatric Rating Scale
      and self-reported alcohol consumption were tested in panel logistic models over
      five ten-week intervals for their concurrent and lagged relationship to violence.
      An interaction term between each type of symptom and alcohol use was also tested.
      RESULTS: In models including the amount of alcohol consumed and symptom levels, a
      high level of affective symptoms was associated with violence during the next
      follow-up period only for participants with depression. There was a significant
      interaction between alcohol use and affective symptoms for participants with
      depression. CONCLUSIONS: The relationship of symptoms and alcohol use to
      community violence should be considered in the context of the individual's
      primary diagnosis. Further characterization of interactions between symptoms and
      substance use in relation to violent behavior may allow for more effective
      assessment of risk state and interventions for violence prevention.

PMID- 22388532
TI  - Asserting prisoners' right to health: progressing beyond equivalence.
AB  - The concept of the "right to health," regardless of a person's legal status, is a
      guiding force in establishing adequate standards of health care for all,
      including prisoners with mental illness. Prison health care in the United States,
      however, often falls below acceptable minimum standards. In the United Kingdom,
      the notion of equivalence has been the main driving force in improving prison
      mental health care. Although improvements have been made over the past ten years,
      demand for services continues to outstrip supply, as in the U.S. prison system.
      In both prison systems, prisoners often present with complex and multiple needs,
      much greater than those found in community samples. Even mental health care
      equivalent to that provided in the community falls significantly short of what is
      required. Further improvements to prison health care, therefore, remain a
      priority, and a more suitable model needs to be established and implemented. The
      authors propose an assertive application of a person's right to health with a
      well-defined framework for health care that is available, accessible, acceptable,
      and of good quality (AAAQ). The authors explore how the AAAQ framework can move
      beyond minimal or equivalent standards to deal with complex prison structures,
      meet health care needs, and measure progress more effectively. The AAAQ framework
      could lead to more equitable standards of health care that can be applied to
      international settings.

PMID- 22388533
TI  - Commentary: treatment for prisoners: a U.S. perspective.

PMID- 22388534
TI  - Recovery as the new medical model for psychiatry.
AB  - Treatment grounded in recovery principles is often viewed as not being based on
      the "medical model." In this Open Forum the author asserts that recovery from
      mental illness is entirely compatible with concepts of recovery from medical
      illness and with new approaches to medical treatment. Three ways of
      conceptualizing recovery are defined: clinical recovery, illness management, and
      personal recovery. Basing treatment on recovery principles is supported by
      research that has shown significant remission rates over time among persons with
      schizophrenia. The author uses examples of public figures and of one family with
      physical disabilities to illustrate the progress society has made toward
      accepting and including people with physical illness and disability. Recovery
      oriented mental health treatment parallels the move in other medical specialties
      toward person-centered care. A clinical approach to promote recovery is
      discussed.

PMID- 22388535
TI  - A consultation service to support participants in psychiatric research.

PMID- 22388536
TI  - A Web-based intervention for alcohol misuse in VA primary care.

PMID- 22388537
TI  - How many authors is too many?

PMID- 22388539
TI  - Shortage or maldistribution?

PMID- 22388541
TI  - Unexpectedly low cholesterol levels among New York State inpatients.

PMID- 22388542
TI  - Peer-led Recovery International groups for mental health consumers.

PMID- 22388543
TI  - One in five U.S. adults had a diagnosable mental disorder in the past year,
      survey finds.

PMID- 22388546
TI  - Photochemical studies on aromatic gamma,delta-epoxy ketones: efficient synthesis
      of benzocyclobutanones and indanones.
AB  - Irradiation of terminal aromatic gamma,delta-epoxy ketones with a 450 W UV lamp
      led to Norrish type II cyclization/semi-pinacol rearrangement cascade reaction
      which formed the benzocyclobutanones containing a full-carbon quaternary center,
      whereas irradiation of substituted aromatic gamma,delta-epoxy ketones led to the
      indanones through a photochemical epoxy rearrangement and 1,5-biradicals
      cyclization tandem reaction.

PMID- 22388545
TI  - Relative expression of TAp73 and DeltaNp73 isoforms.
AB  - The transcription factor p73 belongs to the p53 family of tumour suppressors and
      similar to other family members, transcribed as different isoforms with opposing
      pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare
      in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73
      isoforms are commonly inhibited by over-expression of the dominant negative p73
      isoforms. Therefore the relative ratio of different p73 isoforms is critical for
      the cellular response to a chemotherapeutic agent. Here, we analysed the
      expression of N-terminal p73 isoforms in cell lines and mouse tissues. Our data
      showed that the transcriptionally competent TAp73 isoform is abundantly expressed
      in cancer cell lines compared to the dominant negative DeltaNp73 isoform.
      Interestingly, we detected higher levels of DeltaNp73 in some mouse tissues,
      suggesting that DeltaNp73 may have a physiological role in these tissues.

PMID- 22388547
TI  - [Severe dysphagia following radiochemotherapy of nasopharyngeal carcinoma].

PMID- 22388548
TI  - American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer
      cell growth via cell cycle arrest by modulating expression of cell cycle
      regulators.
AB  - Prostate cancer is one of the most common cancers in the world, and its
      prevalence is expected to increase appreciably in the coming decades. As such,
      more research is necessary to understand the etiology, progression and possible
      preventative measures to delay or to stop the development of this disease.
      Recently, there has been interest in examining the effects of whole extracts from
      commonly harvested crops on the behaviour and progression of cancer. Here, we
      describe the effects of whole cranberry extract (WCE) on the behaviour of DU145
      human prostate cancer cells in vitro. Following treatment of DU145 human prostate
      cancer cells with 10, 25 and 50 MUg ml-1 of WCE, respectively for 6 h, WCE
      significantly decreased the cellular viability of DU145 cells. WCE also decreased
      the proportion of cells in the G2-M phase of the cell cycle and increased the
      proportion of cells in the G1 phase of the cell cycle following treatment of
      cells with 25 and 50 MUg ml-1 treatment of WCE for 6 h. These alterations in cell
      cycle were associated with changes in cell cycle regulatory proteins and other
      cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A,
      cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes
      in p16(INK4a) and pRBp107 protein expression levels also were evident, however,
      the changes noted in p16(INK4a) and pRBp107 protein expression levels were not
      statistically significant. These findings demonstrate that phytochemical extracts
      from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of
      human prostate cancer cells in vitro and further support the potential health
      benefits associated with cranberries.

PMID- 22388549
TI  - Management of blood pressure in children.
AB  - PURPOSE OF REVIEW: This review summarizes recent insights into the epidemiology
      of primary hypertension in children, with emphasis on the most important risk
      factors for the development of hypertension, and also updates current options for
      treating primary hypertension in children. RECENT FINDINGS: There is growing
      evidence that the prevalence of hypertension has increased over the past decade
      and that the epidemic of obesity has played a key role in the increase of blood
      pressure (BP) in the USA and abroad. Recent studies have shown that in addition
      to obesity, environmental factors such as second-hand smoking and sedentary
      lifestyle are important in development of hypertension even in preschool age
      children. Studies also have confirmed the effect of vegetables and fruits on
      lowering BP. Recent clinical trials of valsartan and olmesartan have provided
      efficacy and safety information for use in children. SUMMARY: The increased
      prevalence of hypertension in children in recent years emphasizes the need for a
      more aggressive approach to screen and diagnose elevated BP even in early
      childhood. Early initiation of treatment is important to decrease the risk of
      cardiovascular morbidity in adulthood.

PMID- 22388550
TI  - Mammalian target of rapamycin signaling in the podocyte.
AB  - PURPOSE OF REVIEW: Mammalian target of rapamycin (mTOR) is an evolutionarily
      conserved protein kinase. mTOR forms two distinct functional multiprotein kinase
      complexes that mutually phosphorylate different substrates and regulate a wide
      array of essential cellular processes including translation, transcription and
      autophagy. mTOR is active in several types of cancer and plays a role in a
      variety of other serious human diseases, including diabetes, neurodegenerative
      disorders and polycystic kidney disease. However, until recently, only very
      little was known about the function of mTOR in glomerular homeostasis. RECENT
      FINDINGS: Emerging studies highlight the important roles of the mTOR signaling
      pathway in both maintaining and deregulating glomerular and podocyte function.
      SUMMARY: Here we review the current understanding of mTOR signaling in podocyte
      biology and discuss its implications for the development of glomerular diseases.

PMID- 22388551
TI  - The glomerular endothelium:  new insights on function and structure.
AB  - PURPOSE OF REVIEW: It is our aim to review the latest findings on the intricate
      functional and structural properties of the glomerular endothelium. Previously,
      all focus has been on the podocyte and the glomerular basement membrane (GBM),
      but it is now clear that the endothelium plays an important part of the
      glomerular barrier. RECENT FINDINGS: We start by giving an overview of recent
      findings on the glomerular 'endothelial surface layer' (ESL). The ESL has a
      membrane-bound component, the 'glycocalyx', and a more loosely attached 'cell
      coat' bound by charge-charge interactions. Damage to the ESL causes proteinuria
      even if the GBM and the podocytes are intact. Such damage can be caused by, for
      example, enzymatic digestion of the ESL by increased oxidative stress, or
      secondary to pathological conditions such as high glucose concentration. Indeed,
      several studies suggest the ESL to be targeted in diabetes. The correlation is
      likely to be causal, but the experimental evidence is still indirect. Also, there
      have been new findings on vascular endothelial growth factor, as well as studies
      on angiopoietin and angiopoietin-like proteins demonstrating a key role of the
      endothelium in glomerular disease. SUMMARY: More conclusive endothelium-specific,
      inducible transgenic mouse models are still lacking. There are studies, however,
      showing that the glomerular cell components interact much more intensely than
      previously recognized. Thus, the glomerular barrier seems to maintain its highly
      selective properties by an orchestra of intercellular signaling between
      mesangial, endothelial and epithelial cells. The result resembles a fine-tuned
      symphony of which we have heard only small parts, and understood even less.

PMID- 22388552
TI  - The pathogenesis of membranous nephropathy:  evolution and revolution.
AB  - PURPOSE OF REVIEW: The morphological features of membranous nephropathy have been
      recognized for over five decades, but the pathogenetic mechanisms underlying this
      lesion in humans have only recently been elucidated. This review analyzes the
      recent developments in understanding the pathogenesis of the primary and
      secondary forms of membranous nephropathy. RECENT FINDINGS: Seminal studies have
      identified several autologous antigens that are targets of an autoantibody
      response in primary membranous nephropathy. The leading candidate autoantigen is
      M-type phospholipase A2 receptor (PLA2R) protein. Autoantibodies to PLA2R,
      usually of IgG4 subclass, are found in 70-80% of patients with primary membranous
      nephropathy, bind to conformational epitopes on PLA2R expressed in the glomerular
      podocyte, form immune complexes in situ and induce proteinuria, mostly likely via
      local activation of complement. The autoimmune response is governed by genes at
      the HLA-DQA1 locus. The level of autoantibody to PLA2R correlates with the
      severity of the clinical disease and predicts recurrences in renal allografts (at
      least in some patients). Most forms of secondary membranous nephropathy appear to
      be due to distinctly different pathogenetic mechanisms. SUMMARY: The
      identification of target antigens provides new tools for diagnosis, prognosis and
      monitoring of therapy in human membranous nephropathy.

PMID- 22388553
TI  - Pathologic features of antibody-mediated rejection in renal allografts:  an
      expanding spectrum.
AB  - PURPOSE OF REVIEW: This review discusses recent findings that are changing and
      expanding the spectrum of pathologic changes associated with antibodies directed
      against renal allografts. RECENT FINDINGS: This review focuses on four lesions:
      subclinical antibody-mediated rejection (AMR), C4d-negative AMR, intimal
      arteritis, and arterial intimal fibrosis. A number of studies have identified
      morphologic lesions of AMR in protocol biopsies of normally functioning renal
      allografts, particularly in sensitized recipients, that correlate with subsequent
      development of chronic changes in the graft, including transplant glomerulopathy.
      These same studies as well as molecular studies of indication biopsies of
      conventional renal allografts have noted evidence of microvascular injury, which,
      in the presence of donor-specific antibodies (DSAs) but the absence of C4d
      deposition in peritubular capillaries, is associated with development of
      transplant glomerulopathy and graft loss. Finally, recent studies suggest that
      intimal arteritis, previously felt to represent a lesion of cell-mediated
      rejection, and bland arterial intimal fibrosis, resembling arteriosclerosis, may
      in some cases be manifestations of DSA-induced graft injury. SUMMARY:
      Incorporation of these newly recognized lesions of AMR into a working diagnostic
      schema with sufficient sensitivity and specificity to minimize undertreatment and
      overtreatment of patients is an important challenge currently faced by renal
      pathologists and transplant clinicians.

PMID- 22388554
TI  - Clinical spectrum and pathogenesis of nephronophthisis.
AB  - PURPOSE OF REVIEW: Nephronophthisis (NPH) comprises a group of autosomal
      recessive cystic kidney diseases and is the most frequent genetic cause of end
      stage renal disease in children and adolescents. Causative mutations in more than
      a dozen genes have been identified that encode for the NPH protein family. Almost
      all of these proteins localize to primary cilia leading to the classification of
      NPH as a ciliopathy. The purpose of this review is to highlight the latest
      research on the molecular pathogenesis of the ciliopathy NPH. RECENT FINDINGS:
      Recent identification of novel disease causing genes and research on the
      localization and signaling function of nephrocystins have paved the way to a more
      detailed understanding of the molecular and cellular pathology of NPH and
      associated ciliopathies. SUMMARY: Here we discuss the most recently identified
      NPH related genes, the role of the NPH protein complex in ciliary biology and
      recently discovered functions of NPH proteins in cellular signaling.

PMID- 22388555
TI  - Epidemiology, geography and chronic kidney disease.
AB  - PURPOSE OF REVIEW: Geographic variation in the occurrence and outcomes of chronic
      kidney disease (CKD) is major area of study in epidemiology and health services
      and outcomes research. Geographic attributes may be as diverse as the physical,
      socioeconomic, and medical care characteristics of an environment. This review
      summarizes the recent literature pertaining to geographic risk factors and CKD.
      RECENT FINDINGS: Studies have reported on the association between CKD and
      physical attributes of place (ambient temperature and altitude), the impact of
      disasters on CKD populations, new diseases characterized by regional
      localization, national variations in CKD incidence and prevalence, regional
      variation in end-stage renal disease incidence, residential mobility and CKD risk
      factors, and geographic variations in CKD care. The emerging role of tools for
      geospatial studies - including multilevel analytical designs, which reduce the
      likelihood of an ecologically biased inference, and geographic information
      systems, which allow the simultaneous linkage, analysis, and mapping of
      geospatial data - is illustrated by these studies. SUMMARY: Our understanding of
      the occurrence and outcomes of CKD will continue to be expanded and deepened by
      the explicit study of attributes associated with place as a potential risk
      factor. Many of the studies reviewed are largely hypothesis generating, and a
      better understanding of the role of geography in the study of CKD awaits
      investigations that probe the mechanisms that link attributes of place to disease
      processes.

PMID- 22388556
TI  - Timing of initiation of dialysis:  time for a new direction?
AB  - PURPOSE OF REVIEW: The past 15 years have seen tremendous growth in the
      initiation of dialysis at higher levels of kidney function in the setting of
      mixed evidence and at great societal economic cost. We review recent data on the
      early dialysis initiation trend, the clinical and economic impact of early
      dialysis initiation and the future implications for the management of advanced
      chronic kidney disease (CKD). RECENT FINDINGS: The percentage of patients who
      initiate dialysis with an estimated glomerular filtration rate (eGFR) above 10 
      ml/min/1.73m(2) is now greater than 50%, including 20% who initiate with an eGFR
      above 15 ml/min/1.73m(2). The drivers behind these findings are probably diverse
      but recent literature does not seem to support a higher symptom burden among the
      ageing CKD population as the major cause. The Initiating Dialysis Early And Late
      (IDEAL) trial provides guidance on the safety of waiting for symptoms or lower
      levels of estimated glomerular filtration rate prior to beginning dialysis. In
      addition, economic analyses based on the IDEAL and US Renal Data System findings
      suggest that significant cost savings could be achieved by reversing the early
      initiation trend. SUMMARY: These findings should help clinicians and policy
      makers looking to rein in costs while maintaining the quality of CKD care.

PMID- 22388557
TI  - Diverging racial and ethnic disparities in access to physician care: comparing
      2000 and 2007.
AB  - OBJECTIVE: To examine recent changes in racial and ethnic disparities in access
      to physician services in the United States, and investigate the economic factors
      driving the changes observed. METHODS: Using nationally representative data on
      adults aged 25-64 from the 2000 and 2007 Medical Expenditure Panel Survey, we
      examine changes in two measures of access: whether the individual reported having
      a usual source of care, and whether he/she had any doctor visits during the past
      year. In each year, we calculate disparities in access between African Americans
      and Whites, and between Hispanics and Whites, applying the Institute of
      Medicine's definition of a disparity. Nonlinear regression decomposition
      techniques are then used to quantify how changes in personal characteristics,
      comparing 2000 and 2007, helped shape the changes observed. RESULTS: Large
      disparities in access to physician care were evident for both minority groups in
      2000 and 2007. Disparities in no doctor visits during the past year diminished
      for African Americans, but disparities in both measures worsened sharply for
      Hispanics. CONCLUSIONS: Disparities in access to physician care are improving for
      African Americans in one dimension, but eroding for Hispanics in multiple
      dimensions. The most important contributing factors to the growing disparities
      between Hispanics and Whites are health insurance, education, and income
      differences.

PMID- 22388558
TI  - Copper(I) acetate-catalyzed azide-alkyne cycloaddition for highly efficient
      preparation of 1-(pyridin-2-yl)-1,2,3-triazoles.
AB  - A highly efficient copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of 6
      substituted tetrazolo[1,5-a]pyridines was developed for the preparation of 1
      (pyridin-2-yl)-1,2,3-triazoles by simply using copper(I) acetate as a catalyst.
      The in situ formed HOAc played important dual roles and an activation of 2
      azidopyridine-copper(I) complex was observed.

PMID- 22388561
TI  - Position-dependent image characteristics of a CCD-based full-field digital
      mammography system.
AB  - Full-field digital mammography imaging systems have been investigated
      extensively. However, most investigations focus on the quality assessment of the
      entire image. In this article, we present the results of experimental
      measurements on the position-dependent image characteristics of a CCD array-based
      digital imaging system. Objective image quality parameters such as noise power
      spectrum (NPS) and signal-to-noise ratio (SNR), which are also frequency
      dependent, are employed for this investigation. The image detector uses 12 CCDs
      arranged in a 4 * 3 array to cover a field of 18 cm * 24 cm with a single x-ray
      exposure. Totally 18 sub-areas were chosen as the regions-of-interest (ROIs) for
      each full-field image to study position-dependent characteristics. Our
      experimental results indicate that the image quality at different positions of
      the full-field image exhibit slightly variance due to the characteristic
      diversity of the CCDs and due to the oblique angle of the ROIs to the x-ray
      source. The image seams caused by the physical gaps between adjacent CCDs do not
      increase the noise components significantly to the composite full-field image.
      The x-ray energy-dependence of NPS and SNR was also studied.

PMID- 22388559
TI  - Standardized generation and differentiation of neural precursor cells from human
      pluripotent stem cells.
AB  - Precise, robust and scalable directed differentiation of pluripotent stem cells
      is an important goal with respect to disease modeling or future therapies. Using
      the AggreWellTM400 system we have standardized the differentiation of human
      embryonic and induced pluripotent stem cells to a neuronal fate using defined
      conditions. This allows reproducibility in replicate experiments and facilitates
      the direct comparison of cell lines. Since the starting point for EB formation is
      a single cell suspension, this protocol is suitable for standard and novel
      methods of pluripotent stem cell culture. Moreover, an intermediate population of
      neural precursor cells, which are routinely >95% NCAM(pos) and Tra-1-60(neg) by
      FACS analysis, may be expanded and frozen prior to differentiation allowing a
      convenient starting point for downstream experiments. 

PMID- 22388562
TI  - Feldkamp-type image reconstruction from equiangular data.
AB  - The cone-beam approach for image reconstruction attracts an increasing attention
      in various applications, especially medical imaging. Previously, the traditional
      practical cone-beam reconstruction method, the Feldkamp algorithm, was
      generalized into the case of spiral/helical scanning loci with equispatial cone
      beam projection data. In this paper, we formulated the generalized Feldkamp
      algorithm in the case of equiangular cone-beam projection data, and performed
      numerical simulation to evaluate the image quality. Because medical multi
      slice/cone-beam CT scanners typically use equiangular projection data, our new
      formula may be useful in this area as a framework for further refinement and a
      benchmark for comparison.

PMID- 22388563
TI  - Total reflection X-ray topography for the observation of misfit dislocation
      strain at the surface of a Si/Ge-Si heterostructure.
AB  - Synchrotron X-Ray Topography has been used in Total Reflection Topography (TRT)
      mode to observe strain induced surface bumps due to the presence of underlying
      misfit dislocations in strained layer SiGe on Si epitaxial heterostructures. In
      these experiments the x-rays approached the sample surfaces at grazing incident
      angles below the total external reflection critical angles for a number of
      reflections and hence surface strain features nominally less than a few tens of
      Angstroms from the sample surface have been observed. These are similar to the
      surface bumpiness observed by Atomic Force Microscopy, albeit on a much larger
      lateral length scale. The fact that TRT mode images were taken was confirmed by
      the observation of clear and conventional back reflection topographic images of
      misfit dislocations in all samples when the grazing incidence angle became
      greater than the critical angle.

PMID- 22388564
TI  - A matricial theory of soft x-ray resonant transition radiation in periodic
      multilayer structures.
AB  - When a charged particle crosses an interface between two different materials,
      electromagnetic radiation called Transition Radiation is emitted. The spectrum of
      this radiation extends up to x-ray domain. The Resonant Transition Radiation
      (R.T.R.) can be observed with a periodic arrangement of interfaces. The R.T.R. in
      the soft x-ray range has been recently measured by K. Yamada and coll. with a
      Nickel-Carbon multilayer structure [1]. In this paper, a rigorous electromagnetic
      theory of the R.T.R in finite and infinite multilayer structures is developed
      using the matricial formalism and compared with the experimental quoted data [1].

PMID- 22388566
TI  - No credible consciousness without critical thinking.

PMID- 22388567
TI  - Influence of dentures on SAR in the visible Chinese human head voxel phantom
      exposed to a mobile phone at 900 and 1800 MHz.
AB  - To investigate the influence of dentures on electromagnetic energy absorption
      during the daily use of a mobile phone, a high-resolution head phantom based on
      the Visible Chinese Human dataset was reconstructed. Simulations on phantoms with
      various dentures were performed by using the finite-difference time-domain method
      with a 0.47 wavelength dipole antenna and a mobile phone model as radiation
      sources at 900 and 1800 MHz. The Specific energy Absorption Rate (SAR) values
      including 1 and 10 g average SAR values were assessed. When the metallic dental
      crowns with resonance lengths of approximately one-third to one-half wavelength
      in the tissue nearby are parallel to the radiation source, up to 121.6% relative
      enhancement for 1 g average SAR and 17.1% relative enhancement for 10 g average
      SAR are observed due to the resonance effect in energy absorption. When the
      radiation sources operate in the normal configuration, the 10 g average SAR
      values are still in compliance with the basic restrictions established by the
      Institute of Electrical and Electronic Engineers (IEEE) and the International
      Commission on Non-Ionizing Radiation Protection (ICNIRP), indicating that the
      safety limits will not be challenged by the usage of dentures.

PMID- 22388568
TI  - Two-photon fluorescent probe for cadmium imaging in cells.
AB  - A novel two-photon excited fluorescent probe for cadmium (named as TPCd) was
      designed and synthesized utilizing a prodan (6-acetyl-2-methoxynaphthalene)
      derivative as the two-photon fluorophore and an o-phenylenediamine derivative as
      the Cd(2+) chelator, which possessed favorable photophysical properties and good
      water-solubility. The probe was designed with a photoinduced electron transfer
      (PET) mechanism and thus was weakly fluorescent itself. After binding with Cd(2+)
      which blocked the PET process, the fluorescence intensity of the probe was
      enhanced by up to 15-fold under one-photon excitation (OPE) and 27-fold under two
      photon excitation (TPE), respectively. The two-photon action cross-section
      (Phidelta) of the TPCd-Cd complex at 740 nm reached 109 GM compared to 3.6 GM for
      free TPCd, indicating the promising prospect of the probe in two-photon
      application. TPCd chelated Cd(2+) with 1 : 1 stoichiometry, and the apparent
      dissociation constant (K(d)) was 6.1 * 10(-5) M for the one-photon mode and 7.2 *
      10(-5) M for the two-photon mode. The probe responded to Cd(2+) over a wide
      linear range from 0.1 to 30 MUM with a detection limit of 0.04 MUM. High
      selectivity of the probe towards Cd(2+) was acquired in Tris-HCl/sodium phosphate
      buffer. The probe was pH-independent in the biologically relevant pH range and
      non-toxic to living cells at reasonable concentration levels, warranting its in
      vivo applications. Through two-photon microscopy imaging, the probe was
      successfully applied to detect Cd(2+) uptake in living HepG2 cells.

PMID- 22388569
TI  - Spatial organization and stoichiometry of N-terminal domain-mediated
      glycosyltransferase complexes in Golgi membranes determined by fret microscopy.
AB  - The functional link between glycolipid glycosyltransferases (GT) relies on the
      ability of these proteins to form organized molecular complexes. The
      organization, stoichiometry and composition of these complexes may impact their
      sorting properties, sub-Golgi localization, and may determine relative efficiency
      of GT in different glycolipid biosynthetic pathways. In this work, by using
      Forster resonance energy transfer microscopy in live CHO-K1 cells, we
      investigated homo- and hetero-complex formation by different GT as well as their
      spatial organization and molecular stoichiometry on Golgi membranes. We find that
      GalNAcT and GalT2 Ntd are able to form hetero-complexes in a 1:2 molar ratio at
      the trans-Golgi network and that GalT2 but not GalNAcT forms homo-complexes.
      Also, GalNAcT/GalT2 complexes exhibit a stable behavior reflected by its
      clustered lateral organization. These results reveals that particular topological
      organization of GTs may have functional implications in determining the
      composition of glycolipids in cellular membranes.

PMID- 22388570
TI  - Role of nanotechnology in agriculture with special reference to management of
      insect pests.
AB  - Nanotechnology is a promising field of interdisciplinary research. It opens up a
      wide array of opportunities in various fields like medicine, pharmaceuticals,
      electronics and agriculture. The potential uses and benefits of nanotechnology
      are enormous. These include insect pests management through the formulations of
      nanomaterials-based pesticides and insecticides, enhancement of agricultural
      productivity using bio-conjugated nanoparticles (encapsulation) for slow release
      of nutrients and water, nanoparticle-mediated gene or DNA transfer in plants for
      the development of insect pest-resistant varieties and use of nanomaterials for
      preparation of different kind of biosensors, which would be useful in remote
      sensing devices required for precision farming. Traditional strategies like
      integrated pest management used in agriculture are insufficient, and application
      of chemical pesticides like DDT have adverse effects on animals and human beings
      apart from the decline in soil fertility. Therefore, nanotechnology would provide
      green and efficient alternatives for the management of insect pests in
      agriculture without harming the nature. This review is focused on traditional
      strategies used for the management of insect pests, limitations of use of
      chemical pesticides and potential of nanomaterials in insect pest management as
      modern approaches of nanotechnology.

PMID- 22388571
TI  - Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus
      jostii K01-B0171.
AB  - The biosynthetic gene cluster for lariatins A and B, anti-mycobacterial peptide
      antibiotics with a unique "lasso" structure, was cloned from Gram-positive
      bacterium Rhodococcus jostii K01-B0171. Random transposition mutagenesis using
      IS1415 derivative was carried out to identify a chromosomal locus involved in
      lariatin biosynthesis and six independent lariatin non-producing variants were
      obtained. Arbitrary PCR revealed that one insertion was located near the region
      involved in lariatin biosynthesis. Using the lariatin gene as a probe, a genomic
      library of R. jostii K01-B0171 was screened by colony hybridization, and two
      clones were obtained. Sequence analysis of these clones revealed that the gene
      cluster for lariatin biosynthesis spanning about 4.5 kb consisted of five open
      reading frames (larA to larE). We proposed that the linear precursor LarA is
      processed by LarB, LarC, and LarD, and the mature lariatin is exported by LarE.

PMID- 22388572
TI  - Adolescents and young adults with acute lymphoblastic leukemia have a better
      outcome when treated with pediatric-inspired regimens: systematic review and meta
      analysis.
AB  - Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of
      pediatric patients. Strategies to improve the outcome of adult population are
      warranted. This study aims to evaluate the efficacy and safety of pediatric
      inspired regimens given to adolescents and young adults (AYA), usually defined as
      16-39 years, with ALL. Systematic review and meta-analysis of comparative trials
      of AYA patients with ALL given induction chemotherapy with either pediatric
      inspired regimens or conventional-adult chemotherapy was conducted. Relative
      risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Our
      search yielded 11 trials, including 2,489 patients. AYA patients given pediatric
      inspired regimens had a statistically significant lower all cause mortality rate
      at 3 years (RR 0.58; 95% CI 0.51-0.67). Complete remission rate after induction
      chemotherapy and event free survival were superior in the pediatric-inspired
      regimens arm (RR 1.05; 95% CI 1.01-1.10 and RR 1.66; 95% CI 1.39-1.99,
      respectively). Relapse rate was also lower in patients given pediatric-inspired
      regimens (RR 0.51; 95% CI 0.39-0.66) with comparable nonrelapse mortality between
      the two groups (RR 0.53, 95% CI 0.19-1.48). Pediatric-inspired regimens are
      superior to conventional-adult chemotherapy in AYA ALL patients. Further
      randomized controlled studies to investigate this approach in adult ALL patients
      are warranted.

PMID- 22388575
TI  - Potassium iodide capsule treatment of feline sporotrichosis.
AB  - Sporotrichosis is a mycosis caused by Sporothrix schenckii. The most affected
      animal is the cat; it has played an important role in the zoonotic transmission
      of this disease, especially in Rio de Janeiro, Brazil, since 1998. In order to
      evaluate the treatment of feline sporotrichosis with potassium iodide, an
      observational cohort was conducted in 48 cats with sporotrichosis at Instituto de
      Pesquisa Clinica Evandro Chagas, Fiocruz. All cats received potassium iodide
      capsules, 2.5 mg/kg to 20 mg/kg q24h. The cure rate was 47.9%, treatment failure
      was 37.5%, treatment abandonment was 10.4% and death was 4.2%. Clinical adverse
      effects were observed in 52.1% of the cases. Thirteen cats had a mild increase in
      hepatic transaminase levels during the treatment, six of them presented clinical
      signs suggestive of hepatotoxicity. Compared to previous studies with
      itraconazole and iodide in saturated solution, potassium iodide capsules are an
      alternative for feline sporotrichosis treatment.

PMID- 22388573
TI  - Using PDE inhibitors to harness the benefits of calorie restriction: lessons from
      resveratrol.
AB  - In conclusion, the discovery of the resveratrol-PDE link suggests that PDE4
      inhibitors, possibly in combination with other PDE inhibitors, may be useful for
      mimicking CR and for treating aging-related diseases.

PMID- 22388577
TI  - Organs-on-chips: breaking the in vitro impasse.
AB  - In vitro models of biological tissues are indispensable tools for unraveling
      human physiology and pathogenesis. They usually consist of a single layer of a
      single cell type, which makes them robust and suitable for parallelized research.
      However, due to their simplicity, in vitro models are also less valid as true
      reflections of the complex biological tissues of the human body. Even though the
      realism of the models can be increased by including more cell types, this will
      inevitably lead to a decrease in robustness and throughput. The constant trade
      off between realism and simplicity has led to an impasse in the development of
      new in vitro models. Organs-on-chips, a class of microengineered in vitro tissue
      models, have the potential to break the in vitro impasse. These models combine an
      artificially engineered, physiologically realistic cell culture microenvironment
      with the potential for parallelization and increased throughput. They are robust,
      because the engineered physiological, organ-level features such as tissue
      organization, geometry, soluble gradients and mechanical stimulation are well
      defined and controlled. Moreover, their microfluidic properties and integrated
      sensors pave the way for high-throughput studies. In this review, we define the
      in vitro impasse, we explain why organs-on-chips have the potential to break the
      impasse and we formulate a view on the future of the field. We focus on the
      design philosophy of organs-on-chips, the integration of technology and biology
      and on how to connect to the potential end-users.

PMID- 22388578
TI  - Favorable gradients with the mitroflow aortic valve prosthesis in everyday
      surgery.
AB  - BACKGROUND: The supra-annular Mitroflow valve has been implanted for over 20
      years, preferably in small aortic roots. Early outcomes and gradients in
      unselected elderly patients receiving aortic valve surgery are reported in this
      study. METHODS: Mitroflow valves were implanted in 190 consecutive patients (70%
      females). Mean age was 75.6 +/- 5.5 years, body mass index was 28.2 +/- 5.3
      kg/m2, and logistic EuroSCORE 17.8 +/- 16.5%. There were 170 single, 17 double,
      and 3 triple valve procedures. Of all, 46.8% of surgeries were performed with
      coronary artery bypass grafting and 39.5% were performed with isolated aortic
      valve replacement (AVR). Rates of redo and endocarditic cases were 14.2 and 4.7%.
      RESULTS: The 19-mm (n = 14), 21-mm (n = 135), and 23-mm (n = 41) valves showed
      mean gradients of 16.1 +/- 7.4 mm Hg, 15.8 +/- 7.1 mm Hg, and 11.6 +/- 4.1 mm Hg,
      respectively, before discharge. Maximum gradients were 27.5 +/- 13.0, 28.4 +/-
      12.6, and 21.6 +/- 7.6 mm Hg, respectively. Correlation between gradients and
      sizes was significant. In-hospital mortality was 12.6% overall (6.7% in isolated
      AVR). The rate of valve-related events was low (mild paravalvular leakage 2.1%,
      neurologic 3.2%, bleeding 3.2%, atrioventricular block 4.2%, no thrombosis).
      CONCLUSION: The Mitroflow valve can be safely implanted in elderly patients
      undergoing advanced surgical procedures. Gradients were acceptably low even in
      the smallest valves.

PMID- 22388579
TI  - Invited Commentary.

PMID- 22388580
TI  - Evaluation of decortication in patients with chronic tuberculous empyema by three
      dimensional computed tomography densitometry.
AB  - BACKGROUND: Decortication for chronic pleural empyema (CPE) is to restore lung
      volume by removing empyema sac and thickened pleura. Extent of lung volume
      restoration after decortication has been undefined. This study aims to evaluate
      lung volume restoration using densitometry with three-dimensional reconstruction
      computed tomography (CT). METHODS: We studied 23 patients with CPE who underwent
      decortication and follow-up CT. CT and pulmonary function test (PFT) were
      evaluated at a median of 19.1 months postoperatively. The volumes of operated and
      nonoperated lung were measured by pre- and postoperative CT-densitometry.
      Preoperative and postoperative values of lung volumes, PFTs, and thoracic
      asymmetry rates were compared statistically. RESULTS: The mean preoperative
      volumes of operated and nonoperated lung were 1,239 and 2,094 mL, respectively
      and 1,848 and 2,311 mL postoperatively. The postoperative lung expansion rate was
      71% on the operated side (p < 0.001) and 15% on the nonoperated side (p = 0.026).
      The mean improvement rate of total lung volume was 31%. The postoperative value
      of forced vital capacity, forced expiratory volume during 1 second and lung
      diffusion capacity of carbon monoxide improved 28.0%, 27.4% (p < 0.001), and
      17.9% (p < 0.012), respectively. The thoracic asymmetry decreased from 4.3%
      before surgery to 2.8% after surgery (p = 0.026). CONCLUSIONS: With the use of CT
      densitometry, we quantified the changes of each lung volume. Decortication for
      CPE can improve re-expansion of diseased and healthy lung. Improvement of
      nonoperated lung may be due to the overall improvement of chest wall elasticity.
      Coincidentally, we discovered that the improvement of total lung volume was
      positively associated with the improvement of PFT after decortication.

PMID- 22388581
TI  - Imaging pneumonia in immunocompetent and immunocompromised individuals.
AB  - PURPOSE OF REVIEW: The article aims to indicate the current role of radiological
      imaging in immune competent and immunocompromised patients with pneumonia. The
      radiological findings in the most common conditions will be reviewed. RECENT
      FINDINGS: Three basic patterns of radiographic abnormality are recognized: lobar
      (nonsegmental) pneumonia; bronchopneumonia (lobular pneumonia); and interstitial
      pneumonia. The chest radiograph remains the initial radiological investigation.
      Computed tomography (CT) is more sensitive than the chest radiograph. The
      appearances on CT with certain infections such as mycoplasma, invasive
      aspergillosis, and pneumocystis, in the appropriate clinical setting, may allow a
      treatment decision to be made when obtaining fluid or tissue for culture is
      problematical. MRI technology is advancing and this technique may provide an
      option for follow-up of chronic disease in younger patients in whom radiation
      exposure is a concern, but MRI does not yet match CT as a diagnostic test in this
      field. SUMMARY: Radiology retains a key role in diagnosing pneumonia, excluding
      pneumonia, following up patients to check for resolution and to evaluate
      potential complications. The chest radiograph remains the initial examination. CT
      is more sensitive and with certain infections more specific. MRI provides an
      option for monitoring progress, although cannot yet match CT as an initial
      diagnostic test.

PMID- 22388582
TI  - Severe pneumonia in intensive care:  cause, diagnosis, treatment and management: 
      a review of the literature.
AB  - PURPOSE OF REVIEW: Severe pneumonia is a common disease that intensive care
      physicians have to face. The review highlights recent findings about
      microbiology, diagnosis and treatment, including the management of critically ill
      patients with severe respiratory failure. RECENT FINDINGS: Epidemiological and
      clinical risk factors strongly influence microbiological cause in patients with
      severe pneumonia. In addition to typical respiratory pathogens, less common
      microrganisms and multidrug-resistant (MDR) germs may cause severe lung
      infections. New molecular diagnostic techniques appear promising for early
      detection of microbes involved in severe pneumonia. Antimicrobials remain the
      mainstay of causative severe pneumonia treatment and the optimization of
      antibiotic therapy may be obtained by applying their
      pharmacodynamic/pharmacokinetic properties. Several new strategies have been
      implemented for the management of acute respiratory failure (ARF) due to severe
      pneumonia; however, their extensive clinical application is limited by the need
      for well trained physicians and adequate hospital centers. SUMMARY: Despite
      advancements in antibiotic and life-supportive treatments, severe pneumonia
      remains a leading cause of intensive care unit (ICU) admission and death. Prompt
      and appropriate antimicrobial therapy is essential. The use of new
      nonconventional strategies for ARF management might be effective in more severe
      patients.

PMID- 22388583
TI  - Risk factors associated with pulmonary tuberculosis:  smoking, diabetes and anti
      TNFalpha drugs.
AB  - PURPOSE OF REVIEW: Tuberculosis (TB) remains a global emergency and continues to
      kill 1.4 million people every year. The interaction between noncommunicable and
      infectious diseases like TB has important implications with regard to the
      attainment of the Millennium Development Goals (MDGs). Smoking, diabetes
      mellitus, anti-TNFalpha drugs and other immunosuppressive therapies are well
      known major risk factors associated with TB. The purpose of this review is to
      summarize the recent literature on these risk factors and interventions that
      reduce the risk. RECENT FINDINGS: Mathematical models and aggregate data from the
      field show that smoking, diabetes and anti-TNFalpha drugs independently increase
      the risk of developing active TB. There is consensus on the great need for
      screening for active TB disease in patients with these conditions and targeted
      preventive interventions through a combined multidisciplinary approach. SUMMARY:
      Smoking, diabetes mellitus, anti-TNFalpha drugs and new immunosuppressive
      treatments represent important common risk factors for TB. A high degree of
      clinical awareness of the possibility of TB should be considered in patients with
      these risk factors, and active screening and prevention should be undertaken.
      Further operational research is needed to optimize screening for latent
      Mycobacterium tuberculosis infection, instituting preventive intervention
      measures.

PMID- 22388584
TI  - New therapies for pneumonia.
AB  - PURPOSE OF REVIEW: Acute respiratory tract infections are a key public health
      problem, and represent a major cause of death worldwide. The dramatic shortage of
      new antibiotics combined with the increasing number of antibiotic-resistant
      bacteria constitutes a worrisome threat for the global population and a critical
      challenge for healthcare institutions. Over recent years, a better understanding
      of bacterial growth, metabolism, and virulence has offered several potential
      targets for nonantibiotic antimicrobial therapies. RECENT FINDINGS: Several leads
      have been investigated, targeting adhesion, communication, toxins, virulence
      factors, direct bacterial killing by bacteriophages, and vaccine strategies.
      Promising results have been obtained with these different targets, including
      inhibition of quorum sensing, use of pilicide compounds to inhibit bacterial
      adhesion, prevention and treatment of Pseudomonas aeruginosa pneumonia by
      bacteriophages, effective protection against P. aeruginosa lung infection with
      mucosal vaccination, use of anti-PcrV antibodies in P. aeruginosa-induced sepsis.
      SUMMARY: Expectations are high regarding the translation of these experimental
      results into true clinical benefits for the patients. Importantly, clinical
      studies are ongoing in some areas, and promising preliminary results have already
      been obtained in some instances.

PMID- 22388585
TI  - Necrotizing pneumonia:  a rare complication of pneumonia requiring special
      consideration.
AB  - PURPOSE OF REVIEW: Necrotizing pneumonia is a rare complication of bacterial lung
      infection. Its cause is owing to either a virulence factor of the microorganism
      or a predisposing factor of the host. This disease may cause devastating
      complications such as diffuse pulmonary inflammation, septic shock, and
      respiratory failure, making treatment more difficult. In the recent decade, the
      cause of necrotizing pneumonia and the role of surgical treatment have raised
      considerable attention, leading to therapeutically specific suggestions. RECENT
      FINDINGS: Staphylococcus aureus strains that produce Panton-Valentine leukocidin
      have been reported to cause rapidly progressive necrosis of the lung tissue in
      young immunocompetent patients. Furthermore, recent studies have showed the risk
      of disease progression is associated with underlying medical conditions. Although
      antibiotics are the first choice of treatment for necrotizing pneumonia, it has
      been emphasized that surgical treatment is a feasible alternative option in
      patients who fail to respond to antibiotics and develop continued deterioration
      and complications. SUMMARY: The current knowledge of cause, clinical features,
      diagnosis, treatment, and prognosis of necrotizing pneumonia are summarized.
      Antibiotics remain the mainstay of treatment. Lung resection can be considered an
      alternative treatment option in patients who are unresponsive to antibiotic
      therapy and develop parenchymal complications. Outcome is affected by the degree
      of disease progression and comorbidities.

PMID- 22388586
TI  - Pulmonary infections in transplant recipients.
AB  - PURPOSE OF REVIEW: Hematopoietic stem cell as well as solid-organ transplantation
      is being carried out with increasing frequency throughout the world. Lower
      respiratory tract infections (LRTIs) remain a common life-threatening
      complication faced by the transplant recipients. The purpose of this review is to
      provide up-to-date information on pulmonary infections among the transplant
      recipients, especially emphasizing the endemicity of microorganisms,
      epidemiology, work-up of infections, and principles of their management. RECENT
      FINDINGS: A lower respiratory tract infection such as pneumonia is the most
      frequent of all the infections and is associated with high morbidity and
      mortality. Factors increasing the risk of pulmonary infections include surgical
      techniques, immune status, chemoradiotherapy, alloimmune mechanisms between the
      host and the graft, and the environment. A high degree of suspicion, computed
      tomography (CT) scan of the chest, and flexible bronchoscopy are required in most
      to establish the diagnosis. SUMMARY: Proper management of LRTI in transplant
      recipients requires a high degree of suspicion, thorough knowledge of the
      epidemiology and endemicity of the suspected organisms, CT scan of the chest, and
      expertise at bronchoscopy. Utmost teamwork among transplant physicians,
      infectious disease specialist, and bronchoscopist is essential.

PMID- 22388587
TI  - Update on viral infections in lung transplantation.
AB  - PURPOSE OF REVIEW: Lung transplantation is an established therapeutic option for
      patients with severe respiratory insufficiency. Graft dysfunction or rejection
      depends on the orchestrated prevention of infection(s) and the level of immune
      suppression. More recent reports underlined the role and pathogenicity of
      cytomegalovirus (CMV) infection in lung transplant recipients and the double
      edged sword of maintaining antiviral immune responses versus guided immune
      suppression to avoid graft rejection. We present data concerning the nature of
      the cellular response to Epstein-Barr virus (EBV) and CMV, the subsequent use of
      cellular therapy in antiviral treatment modalities and discuss the role of H1N1
      infection and other viral infections in lung transplantation recipients. RECENT
      FINDINGS: Patients after lung transplantation showed a similar susceptibility to
      H1N1 infections as compared to the local, healthy community. After initial
      recovery and oseltamivir treatment, lung transplantation patients developed
      bronchiolitis obliterans syndrome. The genetic background of lung transplant
      recipients, defined by polymorphism in immune molecules, contributes to increased
      risk of CMV disease; CMV induces local pro-inflammatory chemokines (CXCL10). Anti
      CMV prophylaxis does not impact on anti-CMV-directed cellular immune responses,
      defined by IFNgamma and TNFalpha production. Asymptomatic EBV carriers showed
      higher numbers of EBV-reactive T cells. High EBV load carriers showed T cells
      with immune-exhaustion markers and decreased IFNgamma production. Anti-CMV
      directed cellular therapy may aid to better manage CMV-associated complications
      after lung transplantation. SUMMARY: Pharmacological immune suppression, the
      genetic makeup of the patient as well as concurrent viral infections impact on
      the successful outcome of lung transplantation and call for more detailed immune
      guided diagnostics and therapy.

PMID- 22388588
TI  - Lung infections in the HIV-infected adult.
AB  - PURPOSE OF REVIEW: This review describes current epidemiology, diagnosis,
      treatment and prevention of adult HIV-related lung infections using evidence
      published within the past 2 years. RECENT FINDINGS: Recent evidence has helped
      better determine the importance of early initiation of antiretroviral therapy in
      co-infected individuals with advanced immune suppression. Although this has led
      to a greatly reduced incidence of opportunistic infections in people with HIV,
      Pneumocystis pneumonia remains common. Pneumonia due to bacterial pathogens, such
      as Streptococcus pneumoniae, also causes considerable disease burden, but
      emerging evidence of the clinical efficacy of pneumococcal vaccination,
      especially conjugated vaccines, offers considerable promise. As HIV-infected
      populations become older, more emphasis should be given to the potential benefit
      of influenza prevention, particularly with vaccination, and encouraging smoking
      cessation. Co-infection with tuberculosis is still a huge problem worldwide, but
      the recent development and use of simple clinical algorithms based on symptoms
      and point-of-care testing for recognizing active disease offers great potential.
      SUMMARY: The lung remains an important site of disease in HIV-infected
      individuals. Increasing emphasis should be placed upon prevention of infection
      and modification of risk factors.

PMID- 22388589
TI  - Peer support for postpartum depression: volunteers' perceptions, recruitment
      strategies and training from a randomized controlled trial.
AB  - A randomized controlled trial evaluated the effect of telephone-based peer
      support (mother-to-mother) on preventing postpartum depression among high-risk
      mothers. This paper reports volunteers' perceptions, which showed that peer
      support is an effective preventative intervention. Two-hundred and five (205)
      volunteers were recruited and trained to provide peer support to 349 mothers
      randomized to the intervention group. Volunteers' perceptions were measured at 12
      weeks using the Peer Volunteer Experience Questionnaire, completed by 69% (121)
      of the 175 volunteers who provided support to at least one mother. Large
      majorities felt that the training session had prepared them for their role
      (94.2%), that volunteering did not interfere with their lives (81.8%) and that
      providing support helped them grow as individuals (87.8%). Over 90% stated that
      they would become a peer volunteer again, given the opportunity. Recruitment and
      retention of effective volunteers is essential to the success of any peer-support
      intervention. Results from this study can assist clinicians and program planners
      to provide effective training, sufficient on-going support and evaluation and
      appropriate matching of volunteers to mothers who desire peer support and are at
      high risk of postpartum depression.

PMID- 22388590
TI  - Analysis of inorganic elements in a dacryolith using polarised X-ray fluorescence
      spectrometry: a case report.

PMID- 22388592
TI  - The effect of appointment rescheduling on monitoring interval and patient
      attendance in the glaucoma outpatient clinic.
AB  - AIM: To assess the effect of appointment rescheduling on monitoring intervals and
      patient attendance in the glaucoma clinic. METHODS: A retrospective review of 100
      consecutive patients was conducted. Patients were categorised into groups based
      on risk of progressive visual loss. The monitoring interval requested by the
      clinician was compared with the interval recommended by national guidelines. One
      hundred consecutive patients who had had their appointment rescheduled were also
      examined to assess the effect of appointment rescheduling on the actual
      monitoring interval. Patient non-attendance rates and attendances at the
      emergency department were also examined. RESULTS: After excluding patients with
      secondary glaucoma, glaucoma suspects, and those with short-term factors
      affecting monitoring interval, 54 patients with chronic open-angle glaucoma
      (COAG) were included. Forty-eight (89%) of patients had a monitoring interval
      requested in accordance with national guidelines (2 had longer intervals by 1-2
      months and 4 had shorter time intervals). The monitoring interval was not
      influenced by disease severity (Kruskal-Wallis test, P=0.16), but was
      significantly shorter if the intraocular pressure was above target (P<0.0001) or
      the patient showed structural or functional progression (P<0.0001). Hospital
      initiated appointment rescheduling led to significant lengthening of monitoring
      interval. The mean difference between intended and actual monitoring interval was
      5.6 months. Eight percent (8/100) of patients with rescheduled appointments did
      not attend compared with 15% (39/265) without rescheduled appointments.
      CONCLUSION: Clinical staff are selecting appropriate monitoring intervals for
      patients with COAG; however, hospital-initiated rescheduling of appointments is a
      major challenge to appropriate follow-up.

PMID- 22388591
TI  - Low-grade systemic lymphoma with aggressive transformation in the lacrimal sac.

PMID- 22388593
TI  - Free radicals and the pH of topical glaucoma medications: a lifetime of ocular
      chemical injury?
AB  - INTRODUCTION: Preservatives in ophthalmic preparations are known to cause ocular
      surface damage. Excipients can also contribute to oxidative stress in the
      compromised ocular surface. We evaluated commonly used topical glaucoma
      medications to ascertain pH levels and the intrinsic presence of free radicals.
      METHODS: Samples of 27 topical glaucoma preparations were analysed for total free
      radical presence using a Randox Kit for total antioxidant status. Analytical
      grade indicator paper was used to ascertain pH levels. RESULTS: Free radical
      concentrations for these 27 glaucoma preparations ranged from 0 to 4.54 mmol/l,
      with a median value of 0.66 mmol/l (mean value of 0.662 mmol/l, SD 0.839). Levels
      of pH ranged from 4.0 to 7.4, with a median value of 6.5 (mean 6.252, SD 0.826).
      There was no evidence of a direct correlation between these two variables
      (r=0.232, P=0.275). CONCLUSION: This study is the first to document the range of
      pH and concentrations of free radicals intrinsically present in commonly used
      glaucoma medications. Long-term exposure to preservatives, free radicals, and pH
      levels could all contribute to ocular surface damage. The effect of excipients
      could be responsible for patient intolerance when changing products in the
      compromised ocular surface.

PMID- 22388594
TI  - Traction-induced foveal damage predisposes eyes with pre-existing posterior
      vitreous detachment to idiopathic macular hole formation.
AB  - AIM: To propose a new mechanism for the development of idiopathic macular hole in
      the setting of pre-existing posterior vitreous detachment (PVD). METHODS:
      Patients were examined clinically with fundus contact lens biomicroscopy and high
      definition optical coherence tomography (OCT) was used to characterize the
      structural changes in the fovea following PVD. RESULTS: Two patients presented
      with vitreofoveal separation and were found by high-definition OCT to have subtle
      foveal disruption and irregularity of the foveal contour with no evidence of a
      full thickness macular hole. Sequential examination of these patients
      demonstrated delayed formation of idiopathic macular hole. CONCLUSION: Traction
      induced inner foveal damage occurring before or coincident with spontaneous
      vitreofoveal separation destabilizes the fovea and predisposes some eyes to
      delayed macular hole formation.

PMID- 22388595
TI  - Comparison of postoperative intraocular pressure changes between 23-gauge
      transconjunctival sutureless vitrectomy and conventional 20-gauge vitrectomy.
AB  - PURPOSE: To compare the intraocular pressure (IOP) after 23-gauge
      transconjunctival sutureless vitrectomy (TSV) and conventional 20-gauge
      vitrectomy for various vitreoretinal diseases. METHODS: This was a retrospective
      interventional case series including 338 cases of 23-gauge TSV and 476 cases of
      20-gauge vitrectomy with minimum follow-up period of 1 month. Postoperative 1
      day, 1 week and 1 month IOPs were compared. Multiple regression analysis to
      assess the actual effect of gauge of vitrectomy on postoperative IOP was
      performed including intraoperative and postoperative factors influencing
      postoperative IOP as covariates. RESULTS: The mean IOP of 20-gauge vitrectomy was
      significantly higher than that of 23-gauge TSV (20.6 +/- 8.02 mm Hg vs 12.8 +/-
      4.48 mm Hg, P<0.001) at postoperative day 1, but the differences were not
      significant at postoperative 1 week and 1 month. The IOP pattern of 23-gauge TSV
      demonstrated more stable course than that of 20-gauge vitrectomy. At 1 day post
      vitrectomy, the incidence of hypertony was higher in 20-gauge, whereas that of
      hypotony was higher in 23-gauge. Among risk factors, the 20-gauge vitrectomy
      showed the strongest association with postoperative 1 day IOP rise. CONCLUSION:
      Twenty-three-gauge TSV has stable and lower IOP in the early postoperative period
      than the 20-gauge vitrectomy. In patients whose retina and optic nerves are
      vulnerable to higher or fluctuating IOP, 23-gauge TSV may be more beneficial.

PMID- 22388596
TI  - Persistent central posterior capsule bulging after cataract extraction for
      posterior lenticonus.

PMID- 22388598
TI  - Response to 'Shield or not to shield? Postoperative protection after modern
      cataract surgery'.

PMID- 22388599
TI  - Trocar-assisted sutureless intrascleral posterior chamber foldable intra-ocular
      lens fixation.
AB  - PURPOSE: We report a novel technique characterized by sutureless scleral fixation
      of three-pieces foldable intraocular lens (IOL) using 25-gauge transconjunctival
      sutureless vitrectomy (TSV) trocars in patients with insufficient posterior
      capsule support. MATERIALS AND METHODS: We performed this technique on the eight
      eyes of the seven patients. The scleral tunnels (STs) are prepared by insertion
      of the 25-gauge TSV microcannulas using the trocars, and anterior vitrectomy is
      performed through the clear corneal paracentesis with the aid of anterior chamber
      maintainer (ACM). Finally, the three-piece foldable IOL haptics are incarcerated
      into the prepared STs. RESULTS: The patients were followed up 5-8 months. None of
      the patients had complications such as postoperative endophthalmitis, glaucoma,
      IOL tilt or decentralization, and retinal detachment. Injection of a foldable IOL
      through a clear corneal small incision also contributes the less surgical-induced
      astigmatism. CONCLUSION: The presented novel sutureless scleral IOL fixation
      technique may provide minimal trauma to the surrounding tissues, good IOL
      stabilization decreasing the incidence of IOL tilt along with shorter operation
      time, and postoperative quiet eye.

PMID- 22388601
TI  - Handling drug-related problems in rehabilitation patients: a randomized study.
AB  - BACKGROUND: Drug-related problems (DRPs) have been found to be associated with
      increased morbidity, mortality, and health costs. OBJECTIVE: To investigate
      whether the inclusion of pharmacists in a rehabilitation team influences the
      handling of DRPs in the ward and whether an intervention in hospital affects drug
      use after discharge. SETTING: The rehabilitation ward of a general hospital in
      Oslo, Norway. METHODS: Patients were randomized into an intervention group (IG)
      or a usual care group (CG). The IG patients were followed prospectively by a
      pharmacist, who reviewed the patients' drug therapies using information from
      their medical records and patient interviews. The pharmacist identified DRPs and
      suggested solutions during multidisciplinary team meetings. The IG patients
      received targeted drug counselling from the pharmacist before discharge. The drug
      therapy in the CG, for the period from study randomization to discharge, was
      assessed retrospectively by the pharmacist, who identified DRPs and recorded how
      they were acted upon. Three months after discharge, pharmacists who were blinded
      to the patient randomization, visited the patients at home and interviewed them
      about their medication. MAIN OUTCOME MEASURES: Types and frequencies of DRPs in
      the IG and CG were compared at hospital admission, at discharge, and 3 months
      after discharge. RESULTS: Of the 77 patients included, 40 belonged to the IG and
      37 to the CG. Patient characteristics (IG vs CG) were as follows: age 73.5 versus
      76.8 years; female 58 versus 68%; mean number of drugs at admission 8.3 versus
      7.8; and mean number of drugs at discharge 8.5 versus 7.7. At admission, 4.4 DRPs
      per patient were recorded in the IG and 4.2 in the CG. Significantly more DRPs
      were acted upon and resolved in the IG; at discharge, the IG had 1.2 DRPs per
      patient and the CG had 4.0 (P < 0.01). At the home visit, a significant
      difference between the groups was found: 1.63 versus 2.62 DRPs (P = 0.02) for the
      IG and the CG, respectively. CONCLUSION: Involvement of a pharmacist in drug
      therapy management, including participation in multidisciplinary team
      discussions, markedly improved the identification and resolution of DRPs during a
      hospital stay. The benefit persisted after discharge.

PMID- 22388602
TI  - The global role of kidney transplantation.
AB  - World Kidney Day on March 8th 2012 provides a chance to reflect on the success of
      kidney transplantation as a therapy for end-stage kidney disease that surpasses
      dialysis treatments both for the quality and quantity of life that it provides
      and for its cost effectiveness. Anything that is both cheaper and better, but is
      not actually the dominant therapy, must have other drawbacks that prevent
      replacement of all dialysis treatment by transplantation. The barriers to
      universal transplantation as the therapy for end-stage kidney disease include the
      economic limitations which, in some countries place transplantation,
      appropriately, at a lower priority than public health fundamentals such as clean
      water, sanitation, and vaccination. Even in high-income countries, the technical
      challenges of surgery and the consequences of immunosuppression restrict the
      number of suitable recipients, but the major finite restrictions on kidney
      transplantation rates are the shortage of donated organs and the limited medical,
      surgical, and nursing workforces with the required expertise. These problems have
      solutions which involve the full range of societal, professional, governmental,
      and political environments. World Kidney Day is a call to deliver transplantation
      therapy to the one million people a year who have a right to benefit.

PMID- 22388603
TI  - Chronic allograft dysfunction: major contributing factors.
AB  - Chronic, progressive, and irreversible loss of a transplanted kidney function,
      previously named chronic allograft nephropathy, is the leading cause of chronic
      allograft failure among kidney transplant recipients. Chronic allograft
      dysfunction (CAD) is a multifactorial process associated with progressive
      interstitial fibrosis and tubular atrophy. Current Data confirms that an additive
      series of time-dependent immunological factors such as acute and chronic antibody
      and/or cell-mediated rejection and nonimmunological factors are involved in
      development of interstitial fibrosis and tubular atrophy as the fundamental parts
      of CAD. The use of calcineurin inhibitors has produced a major impact on
      achieving successful organ transplantation; however, although this assumption has
      been doubted recently, calcineurin inhibitors are deemed to be associated with
      nephrotoxicity and subsequent interstitial fibrosis, tubular atrophy, and kidney
      dysfunction. The early fibrotic changes are due to implantation stress, T-cell
      mediated rejection, and infection; however, usually they do not lead to
      progressive fibrosis and allograft dysfunction per se. In the setting of CAD,
      many factors occurring lately after 1 year, such as chronic antibody-mediated
      rejection, recurrent or de novo glomerulonephritis, and nonadherent adequately
      address the existence of ongoing injuries and progression to fibrosis.
      Identification of patients who are at risk, close clinical monitoring, and
      optimization and individualization of their maintenance immunosuppressive regimen
      are among the means that could help us to improve the long-term outcome of kidney
      transplantation.

PMID- 22388604
TI  - The inception and formation of the theory of hyperfiltration through the ages.
AB  - With the rising incidence of metabolic syndrome and progressive kidney disease,
      efforts to halt this progression have become the mainstay of therapies in the era
      of modern nephrology. The necessity of one versus two kidneys has occupied the
      minds of leading scientists and philosophers throughout the ages and has laid the
      foundation for our understanding of progressive kidney disease. This review
      focuses on the major discoveries of the leading thinkers who with their paradigm
      shifting ideas and skepticism pushed the boundaries of our knowledge and shaped
      the theory of hyperfiltration.

PMID- 22388605
TI  - A left jugular vein catheter for hemodialysis malpositioned in right
      brachiocephalic vein.

PMID- 22388606
TI  - Effect of alcoholic extract of Nigella sativa on cisplatin-induced toxicity in
      rat.
AB  - INTRODUCTION: The aim of this study was to test whether Nigella sativa (NS) seeds
      can reduce cisplatin-induced toxicity. MATERIALS AND METHODS: Thirty rats were
      divided into 3 groups to receive distilled water (control group), cisplatin (3
      mg/kg per body weight for 3 days), and cisplatin and alcoholic extract of NS (100
      mg/kg per body weight). Biochemical and histopathologic parameters were compared
      between the three groups on days 14 and 42 of the study. RESULTS: Blood urea
      nitrogen increased in the cisplatin and NS groups on days 14 and 42 compared to
      day 0 (P < .001). It was significantly in the cisplatin than in the control group
      on day 14 (P < .001). Serum creatinine had a similar profile in the cisplatin and
      NS groups as blood urea nitrogen. Serum triglyceride increased in the cisplatin
      and NS groups on day 14, but it decreased on day 42 (P < .05). Urine glucose
      concentration decreased in the cisplatin group on days 14 and 42 compared to day
      0 (P < .001), and the same trend was seen in the NS group (P < .001). Histology
      of the kidneys exposed to cisplatin showed significant kidney injury, but the
      rats treated with NS showed a relatively well-preserved architecture.
      CONCLUSIONS: Cisplatin-induced nephrotoxicity was confirmed in our study. Nigella
      sativa seeds had nonsignificant effects on biochemical parameters, although the
      histopathologic properties of the kidneys relatively recovered after NS use.

PMID- 22388607
TI  - Low prevalence of high-dose methotrexate nephropathy in patients with malignancy.
AB  - INTRODUCTION: Methotrexate is an antifolate medication frequently used in the
      treatment of malignant and nonmalignant diseases. The usage of high-dose
      methotrexate was limited to patients with osteosarcoma, Ewing sarcoma, lymphoma,
      and acute lymphoblastic leukemia. One of the major side effects of high-dose
      methotrexate is nephropathy. The aim of present study was to determine the renal
      side effects of high-dose methotrexate in patients with malignancies. MATERIALS
      AND METHODS: In a study of 102 patients with osteosarcoma (n = 72), Ewing sarcoma
      (n = 15), and lymphoma (n = 15), treated with high-dose methotrexate, clinical
      and laboratory data including kidney function tests were recorded at baseline and
      during follow-up visits. The mean duration of follow-up was 6 months. RESULTS:
      The mean age of the patients was 19.5 years (range, 5 to 80 years). The total
      courses of methotrexate therapy were 273 (median, 2.67 per patient). The mean
      creatinine level was 0.82 mg/dL. Of the 102 patients, 3 (2.9%) developed acute
      kidney injury with an at risk phase. Another patient (1.0%) developed acute
      kidney injury and its phase was injury according to the RIFLE criteria. None of
      the cases were failed and acute kidney injury was alleviated in all of the
      affected patients. CONCLUSIONS: Our data revealed a low prevalence of acute
      kidney injury with high-dose methotrexate therapy. In addition, these toxicities
      were limited to the first and second phases of the RIFLE classification, all of
      which resolved spontaneously.

PMID- 22388608
TI  - Brain hemodynamics in patients with end-stage renal disease between hemodialysis
      sessions.
AB  - INTRODUCTION: End-stage renal disease has been associated with premature
      atherosclerosis of the cerebral circulation. The risk of stroke, a frequent
      complication of uremia as a result of cerebral blood flow reduction, is high in
      dialysis patients. This study aimed to assess brain hemodynamics between
      hemodialysis interval periods by transcranial Doppler ultrasonography. MATERIALS
      AND METHODS: In a case-control study, to evaluate cerebral circulation
      homodynamics, 20 hemodialysis patients and 20 age- gender-matched healthy control
      subjects underwent transcranial Doppler ultrasonography. Blood parameters were
      also measured simultaneously. Among hemodialysis patients, these studies were
      performed 48 hours after a dialysis session. RESULTS: The mean blood flow
      velocity (MV) values were significantly higher in the middle cerebral artery (P =
      .007), anterior cerebral artery (P = .003), posterior cerebral artery-segment 2
      (P = .03), basilar artery (P = .05) in hemodialysis patients compared to the
      controls. The MV had a negative meaningful correlation with hemoglobin and
      hematocrit in most intracranial arteries of the patients, but no significant
      correlation was observed between these variables and MV of the arteries in the
      control group. CONCLUSIONS: The MV of the cerebral arteries significantly
      increases in hemodialysis patients, which could be due to the decrease in
      hemoglobin levels in these patients.

PMID- 22388609
TI  - Prognostic value of dialysis effluent leukocyte count in children on peritoneal
      dialysis with peritonitis.
AB  - INTRODUCTION: Early prediction of the efficacy of treatment in peritonitis
      complicating peritoneal dialysis (PD) is the best way to reduce morbidity. We
      studied the prognostic value of the third-day dialysis effluent leukocyte count
      after antibiotic therapy for prediction of treatment outcomes. MATERIALS AND
      METHODS: Medical records of 31 children on PD, younger than 15 years old,
      admitted in Ali-Asghar Children's Hospital because of PD-related peritonitis,
      were reviewed retrospectively. Peritonitis was defined by fever, abdominal pain,
      and cloudy effluent with a leukocyte count greater than 100/mm3 or a positive
      dialysis effluent culture for microorganisms. For each episode of peritonitis,
      the leukocyte count of the effluent was measured on the third day after
      initiation of empiric therapy and culture results were recorded. The receiver
      operating characteristic curve was used to perform predicting value assessments.
      RESULTS: Of 60 episodes of peritonitis, 68.3% were treated successfully. Of the
      remaining episodes, 15.8% resulted in mortality, 57.9% required catheter removal,
      and 26.3% led to both. The mean PD effluent leukocyte count on the third day
      after initiating empiric antibiotics was significantly higher in the group with
      treatment failure (2258 +/- 796/mm3) than in the group with successful treatment
      (1325 +/- 669/mm3; P < .001). The cutoff point of 1240/mm3 was found with
      optimized sensitivity (100%), specificity (63.4%), positive predictive value
      (55.9%), and negative predictive value (100%) for prediction of treatment failure
      (P < .001). CONCLUSIONS: This study showed that the third-day dialysis effluent
      leukocyte count predicted short outcomes of peritonitis.

PMID- 22388610
TI  - Effect of intradialytic aerobic exercise on serum electrolytes levels in
      hemodialysis patients.
AB  - INTRODUCTION: We aimed determine the impact of an 8-week intradialytic exercise
      program, consisting of 15 minutes of cumulative duration low-intensity exercise
      during the first 2 hours of dialysis on serum electrolytes levels and hemoglobin.
      MATERIALS AND METHODS: In a randomized controlled trial of in an outpatient
      hemodialysis unit, clinically stable hemodialysis patients (n = 47) were included
      and assigned into the aerobic exercise group (n = 25) and the control group (n =
      23). Aerobic exercises were done in groups, 15 min/d, 3 times a week, for 2
      months. The main outcome measures were biochemical variables including serum
      levels of calcium, phosphate, and potassium levels and hemoglobin level. RESULTS:
      After an 8-week intervention, significant improvements were seen in serum
      phosphate levels (decreased by 1.84 mg/dL) and serum potassium levels (decreased
      by 0.69 mg/dL). No side-effects were observed. Serum calcium and hemoglobin
      levels did not change significantly in the exercise group. CONCLUSIONS: A
      simplified aerobic exercise program is a complementary, safe, and effective
      clinical treatment modality in patients with end-stage renal disease on dialysis.

PMID- 22388611
TI  - Primary success of bifurcated vein patch arteriovenous fistula and Brescia-Cimino
      methods.
AB  - INTRODUCTION: For continuous hemodialysis, an appropriate vascular access, mostly
      through an arteriovenous fistula (AVF), is crucial. The Brescia-Cimino (BC)
      method is a common surgical method for AVF creation. However, this method is
      sometimes not possible, due to a small venous diameter or its wide distance from
      the artery. We evaluated the success rate of bifurcated vein patch (BVP)
      technique as an alternative method to BC for AVF placement in hemodialysis
      patients. MATERIALS AND METHODS: Candidates for AVF vascular access for
      hemodialysis were assigned into 2 groups of 50 patients, and AVF was placed using
      the BC method in one group and the BVP method in the other group. Immediate AVF
      thrill after the operation, first-day postoperation thrill, weighting period, and
      nursing staff satisfaction for hemodialysis were compared between the BC and BVP
      methods. RESULTS: Although the weighting period in the BVP group was longer than
      that in the BC group, other parameters were similar between the two groups. The
      AVF thrill intensity after the operation was good to excellent in 87% of the
      cases with the BC method and good in 95% of those with BVP. Satisfaction of
      dialysis nursing staff during hemodialysis was reported as 87% good and 4%
      average in the BC group and 75% good and 20% average in the BVP group.
      CONCLUSIONS: Bifurcated vein patch can be an appropriate alternative technique
      for cases in which the commonly used BC method is not possible for AVF placement.

PMID- 22388612
TI  - Inverse association of serum 25-hydroxyvitamin D with markers of inflammation and
      suppression of osteoclastic activity in hemodialysis patients.
AB  - INTRODUCTION: In hemodialysis patients, 25-hydroxyvitamin D conversion to active
      1,25-dihydroxyvitamin D by the kidneys is very limited. The expression of both
      vitamin D receptor and 1alpha-hydroxylase in cells of the immune system and in
      both osteoblasts and osteoclasts makes it possible that 25-hydroxyvitamin D could
      play an important role in both inflammation and bone metabolism acting in a
      autocrine and/or paracrine way in these patients. MATERIALS AND METHODS: Thirty
      three hemodialysis patients not under vitamin D receptor agonist treatment were
      enrolled into the study. Serum levels of 25-hydroxyvitamin D, C-reactive protein
      (CRP), interleukin-6 (IL-6), receptor activator of nuclear factor-kappaB ligand
      (RANKL), and osteoprotegerin, as well as intact parathyroid hormone were assessed
      by immunoassays. RESULTS: Regarding inflammation, 25-hydroxyvitamin D inversely
      correlated with both CRP and IL-6. Regarding bone metabolism, 25-hydroxyvitamin D
      was positively related to osteoprotegerin, but negatively to the RANKL. The
      latter could be the result of parathyroid hormone suppression by 25
      hydroxyvitamin D, since 25-hydroxyvitamin D negatively correlated with
      parathyroid hormone, which in turn was positively related to RANKL. CONCLUSIONS:
      Serum 25-hydroxyvitamin D is inversely correlated with markers of inflammation
      and may suppress osteoclastic activity in hemodialysis patients.

PMID- 22388613
TI  - Self-esteem in Greek dialysis patients: the contribution of health locus of
      control.
AB  - INTRODUCTION: Chronic kidney disease is a permanent condition which requires
      renal replacement therapy (hemodialysis, peritoneal dialysis, or transplantation)
      to maintain life. The present study aimed to investigate the association of self
      esteem with health locus of control in dialysis patients. MATERIALS AND METHODS:
      A sample of 144 patients was recruited from 3 General Hospitals in the broader
      area of Athens, consisting of 84 patients undergoing in-center hemodialysis and
      60 patients on continuous ambulatory peritoneal dialysis. Measurements were
      conducted with the World Health Organization Quality of Life instrument, in which
      self-esteem is addressed by 1 item, and the Multidimensional Health Locus of
      Control inventory. RESULTS: The results indicated that self-esteem had a
      significant positive association with internal health locus of control. Self
      esteem was also inversely related to the dimension of important others measured
      by the Multidimensional Health Locus of Control inventory. CONCLUSIONS: Findings
      of this study provide evidence that there is a strong relation between self
      esteem and health locus of control in dialysis patients.

PMID- 22388614
TI  - Protective effect of heparin and aspirin against vascular thrombosis in pediatric
      kidney transplants.
AB  - INTRODUCTION: This study was conducted to evaluate preventive effect of a
      combination of heparin and aspirin on vascular thrombosis and kidney transplant
      outcomes of pediatric kidney transplant recipients. MATERIALS AND METHODS: Twenty
      four pediatric kidney transplant recipients received heparin, 50 U/kg, every 8
      hours for 7 postoperative days, and aspirin, 5 mg/kg, thrice a week from day 3 of
      transplantation for 3 months. These patients were compared with a matched group
      of pediatric kidney allograft recipients in terms of development of thrombosis
      and serum creatinine level at 1 year postoperation. RESULTS: The mean age of
      patients was 9.4 +/- 3.2 years. No vascular thrombosis was developed among the 24
      patients with anticoagulant therapy, while in the control group, 5 grafts (7.9%)
      developed thrombosis (P = .19). Serum creatinine levels at 1 year were lower in
      the children with anticoagulant therapy as compared with the controls (P = .02).
      CONCLUSIONS: Our study revealed a reduction in kidney allograft thrombosis
      incidence in children who received heparin and aspirin after transplantation,
      which was clinically important although the difference was not statistically
      significant. Lower serum creatinine levels as compared with a historical cohort
      group were seen 1 year after transplant surgery. These findings are required to
      be confirmed by further studies.

PMID- 22388615
TI  - A child with atypical celiac disease and recurrent urolithiasis.
AB  - A young boy with prior constipation developed recurrent severe calcium phosphate
      kidney calculi, sometimes sufficient to cause acute kidney failure and
      hydronephrosis. After several major surgeries, food allergies were determined by
      serum immunoglobulin E testing, and when he finally went on a gluten-free diet,
      he stopped forming calculi and has had no surgeries related to kidney calculi
      since. Hyperoxaluria was not identified in this child by 24-hour urine analysis,
      unlike most other reports of kidney calculus formation in individuals with gluten
      intolerance.

PMID- 22388616
TI  - Gene polymorphism of complement factor H in a Turkish patient with
      membranoproliferative glomerulonephritis type II.
AB  - Membranoproliferative glomerulonephritis (MPGN) is characterized by proliferation
      of mesangial and endothelial cells and by thickening of the peripheral capillary
      walls. Type II of the MPGN is associated with complement abnormalities which are
      factor H deficiencies due to mutations in the complement factor H (CFH) gene. We
      report a 15-year-old boy diagnosed with MPGN II in whom genetic analyses of the
      CFH gene revealed that the patient was heterozygote for a polymorphism in exon 2
      of the CFH (c.184G>A), heterozygote for a polymorphism in exon 9 of the CFH
      (c.1204C>T),  and heterozygote for a polymorphism in exon 10 of the CFH
      (c.1419G>A). These data recapitulate a prototypical complement genetic profile,
      the presence of major risk factors for MPGN II, which support the hypothesis that
      these dense deposit diseases have a common pathogenic mechanism involving
      dysregulation of the alternative pathway of complement activation.

PMID- 22388617
TI  - Re: Role of electron microscopy in evaluation of native kidney biopsy: a
      retrospective study of 273 cases.

PMID- 22388620
TI  - Gallium-labelled peptides for imaging of inflammation.
AB  - Inflammation plays a major role in the development of many diseases. This review
      article summarizes recent research in the field of in vivo imaging of
      inflammation. Novel methodologies using PET with (68)Ga peptides targeting, for
      example, vascular adhesion protein 1 are discussed.

PMID- 22388621
TI  - Feasibility and availability of 68Ga-labelled peptides.
AB  - (68)Ga has attracted tremendous interest as a radionuclide for PET based on its
      suitable half-life of 68 min, high positron emission yield and ready availability
      from (68)Ge/(68)Ga generators, making it independent of cyclotron production.
      (68)Ga-labelled DOTA-conjugated somatostatin analogues, including DOTA-TOC, DOTA
      TATE and DOTA-NOC, have driven the development of technologies to provide such
      radiopharmaceuticals for clinical applications mainly in the diagnosis of
      somatostatin receptor-expressing tumours. We summarize the issues determining the
      feasibility and availability of (68)Ga-labelled peptides, including generator
      technology, (68)Ga generator eluate postprocessing methods, radiolabelling,
      automation and peptide developments, and also quality assurance and regulatory
      aspects. (68)Ge/(68)Ga generators based on SnO(2), TiO(2) or organic matrices are
      today routinely supplied to nuclear medicine departments, and a variety of
      automated systems for postprocessing and radiolabelling have been developed. New
      developments include improved chelators for (68)Ga that could open new ways to
      utilize this technology. Challenges and limitations in the on-site preparation
      and use of (68)Ga-labelled peptides outside the marketing authorization track are
      also discussed.

PMID- 22388622
TI  - 68Ga-labelled peptides for diagnosis of gastroenteropancreatic NET.
AB  - In the past few years, the introduction of novel PET tracers labelled with (68)Ga
      has changed the diagnostic approach to neuroendocrine tumours (NET) in
      specialized centres. Although somatostatin analogue tracers labelled with (111)In
      have represented the gold standard imaging modality for NET detection in past
      decades, the advantages offered by both labelling somatostatin analogues with
      (68)Ga and using PET/CT tomography for image acquisition, account for the
      increasing use of these tracers in clinical practice. There are an increasing
      number of reports of the higher accuracy of (68)Ga-DOTA peptide PET/CT for the
      detection of NET lesions as compared to morphological imaging procedures and
      somatostatin receptor scintigraphy. Moreover, the use of (68)Ga-DOTA peptides
      offers the possibility to noninvasively evaluate NET cells for the presence of
      somatostatin receptor expression, with direct therapeutic implications. Several
      practical advantages also favour the use of (68)Ga-DOTA peptides including the
      relatively easy and economic synthesis process and the fact that (68)Ga labelling
      can be performed in centres without an on-site cyclotron. We describe the
      advantages and limitations of (68)Ga-DOTA peptide PET/CT imaging for the
      assessment of gastroenteropancreatic NET referring to the available literature as
      well as to our experience, and finally highlight potential future perspectives.

PMID- 22388623
TI  - 68Ga-labelled peptides in the management of neuroectodermal tumours.
AB  - Neuroectodermal tumours arise from chromaffin cells and possess the ability to
      secrete catecholamines. They are generally rare and may occur in association with
      a variety of hereditary syndromes such as MEN-2A and 2B, neurofibromatosis type 1
      and von Hippel-Lindau disease. The most common types are phaeochromocytoma
      arising from the adrenal medulla and paraganglioma of extra-adrenal origin.
      Phaeochromocytomas tend to be benign and are often associated with a gene
      mutation if the disease is bilateral, while paragangliomas are often malignant,
      have a more aggressive nature and tend to metastasize. There are no specific
      histological or immunohistochemical features that indicate the malignant
      potential and the diagnosis of malignancy can only be established by the presence
      of distant metastases. Therefore, imaging can play a vital role in the diagnosis,
      localization, staging and assessment of spread. Traditionally, this is achieved
      with a combination of cross-sectional (CT and MRI) and functional ((123)I-MIBG or
      (111)In-octreotide) imaging. However, these modalities are not adequate and
      achieve moderate sensitivity. The introduction of (68)Ga-DOTA peptide in PET/CT
      imaging has led to improved receptor targeting and superb PET resolution, as well
      as accurate localization of lesions. The use of this technique in neuroectodermal
      tumours has been shown to be superior to all available modalities, but the
      available data are limited and larger studies are awaited to establish its role
      in the management of these tumours.

PMID- 22388625
TI  - Yttrium-labelled peptides for therapy of NET.
AB  - Peptide receptor radionuclide therapy (PRRT) consists in the systemic
      administration of a synthetic peptide, labelled with a suitable beta-emitting
      radionuclide, able to irradiate tumours and their metastases via the
      internalization through a specific receptor, overexpressed on the cell membrane.
      After 15 years of experience, we can state that PRRT with (90)Y-labelled peptides
      is generally well tolerated. Acute side effects are usually mild, some of which
      are related to the co-administration of amino acids, such as nausea. Others are
      related to the radiopeptide, such as fatigue or the exacerbation of an endocrine
      syndrome, which rarely occurs in functioning tumours. Chronic and permanent
      effects on target organs, particularly the kidneys and the bone marrow, are
      generally mild if the necessary precautions are taken. Currently, the potential
      risk to kidney and red marrow limits the amount of radioactivity that may be
      administered. However, when tumour masses are irradiated with adequate doses,
      volume reduction may be observed. (90)Y-octreotide has been the most widely used
      radiopeptide in the first 8-10 years of experience. Unfortunately, all of the
      published results derive from different and inhomogeneous phase I/II studies.
      Hence, a direct comparison is virtually impossible to date. Nevertheless, even
      with these limitations, objective responses are registered in 10-34% of patients.
      The optimal timing of (90)Y-DOTATOC in the management of somatostatin receptor
      (SSTR)-positive tumours and the way in which it should be integrated with other
      treatments have yet to be defined, and prospective phase II/III trials comparing
      the efficacy and toxicity of different schemes of (90)Y-DOTATOC administration
      are still warranted.

PMID- 22388624
TI  - Radiopharmaceutical development of radiolabelled peptides.
AB  - Receptor targeting with radiolabelled peptides has become very important in
      nuclear medicine and oncology in the past few years. The overexpression of many
      peptide receptors in numerous cancers, compared to their relatively low density
      in physiological organs, represents the molecular basis for in vivo imaging and
      targeted radionuclide therapy with radiolabelled peptide-based probes. The
      prototypes are analogs of somatostatin which are routinely used in the clinic.
      More recent developments include somatostatin analogs with a broader receptor
      subtype profile or with antagonistic properties. Many other peptide families such
      as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin,
      arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few
      years and quite a number of potential radiolabelled probes have been derived from
      them. On the other hand, a variety of strategies and optimized protocols for
      efficient labelling of peptides with clinically relevant radionuclides such as
      (99m)Tc, M(3+) radiometals ((111)In, (86/90)Y, (177)Lu, (67/68)Ga), (64/67)Cu,
      (18)F or radioisotopes of iodine have been developed. The labelling approaches
      include direct labelling, the use of bifunctional chelators or prosthetic groups.
      The choice of the labelling approach is driven by the nature and the chemical
      properties of the radionuclide. Additionally, chemical strategies, including
      modification of the amino acid sequence and introduction of linkers/spacers with
      different characteristics, have been explored for the improvement of the overall
      performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics.
      Herein, we discuss the development of peptides as radiopharmaceuticals starting
      from the choice of the labelling method and the conditions to the design and
      optimization of the peptide probe, as well as some recent developments, focusing
      on a selected list of peptide families, including somatostatin, bombesin,
      cholecystokinin/gastrin, GLP-1/exendin and RGD.

PMID- 22388626
TI  - 111In-DTPA0-octreotide (Octreoscan), 131I-MIBG and other agents for radionuclide
      therapy of NETs.
AB  - This paper is a critical review of the literature on NET radionuclide therapy
      with (111)In-DTPA(0)-octreotide (Octreoscan) and (131)I-MIBG, focusing on
      efficacy and toxicity. Some potential future applications and new candidate
      therapeutic agents are also mentioned. Octreoscan has been a pioneering agent for
      somatostatin receptor radionuclide therapy. It has achieved symptomatic responses
      and disease stabilization, but it is now outperformed by the corresponding beta
      emitter agents (177)Lu-DOTATATE and (90)Y-DOTATOC. (131)I-MIBG is the
      radionuclide therapy of choice for inoperable or metastatic
      phaeochromocytomas/paragangliomas, which avidly concentrate this tracer via the
      noradrenaline transporter. Symptomatic, biochemical and tumour morphological
      response rates of 50-89%, 45-74% and 27-47%, respectively, have been reported.
      (131)I-MIBG is a second-line radiopharmaceutical for treatment of
      enterochromaffin carcinoids, mainly offering the benefit of amelioration of
      hormone-induced symptoms. High specific activity, non-carrier-added (131)I-MIBG
      and meta-astato((211)At)-benzylguanidine (MABG) are tracers with potential for
      enhanced therapeutic efficacy, yet their integration into clinical practice
      awaits further exploration. Amongst other promising agents, radiolabelled exendin
      analogues show potential for imaging and possibly therapy of insulinomas, while
      preclinical studies are currently evaluating DOTA peptides targeting the CCK
      2/gastrin receptors that are overexpressed by medullary thyroid carcinoma cells.

PMID- 22388627
TI  - Radiolabelled peptides for oncological diagnosis.
AB  - Radiolabelled receptor-binding peptides targeting receptors (over)expressed on
      tumour cells are widely under investigation for tumour diagnosis and therapy. The
      concept of using radiolabelled receptor-binding peptides to target receptor
      expressing tissues in vivo has stimulated a large body of research in nuclear
      medicine. The (111)In-labelled somatostatin analogue octreotide (OctreoScan) is
      the most successful radiopeptide for tumour imaging, and was the first to be
      approved for diagnostic use. Based on the success of these studies, other
      receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon
      like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and
      RGD peptides are currently under development or undergoing clinical trials. In
      this review, we discuss some of these peptides and their analogues, with regard
      to their potential for radionuclide imaging of tumours.

PMID- 22388629
TI  - Radiolabelled RGD peptides for imaging and therapy.
AB  - Imaging of angiogenesis has become increasingly important with the rising use of
      targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive
      assessment of angiogenic activity is in this respect interesting, e.g. for
      response assessment of such targeted antiangiogenic therapies. One promising
      approach of angiogenesis imaging is imaging of specific molecular markers of the
      angiogenic cascade like the integrin alpha(v)beta(3). For molecular imaging of
      integrin expression, the use of radiolabelled peptides is still the only approach
      that has been successfully translated into the clinic. In this review we will
      summarize the current data on imaging of alpha(v)beta(3) expression using
      radiolabelled RGD peptides with a focus on tracers already in clinical use. A
      perspective will be presented on the future clinical use of radiolabelled RGD
      peptides including an outlook on potential applications for radionuclide therapy.

PMID- 22388630
TI  - Rationale for the use of radiolabelled peptides in diagnosis and therapy.
AB  - Nuclear medicine techniques are becoming more important in imaging oncological
      and infectious diseases. For metabolic imaging of these diseases, antibody and
      peptide imaging are currently used. In recent years peptide imaging has become
      important, therefore the rationale for the use of peptide imaging is described in
      this article. Criteria for a successful peptide tracer are a high target
      specificity, a high binding affinity, a long metabolic stability and a high
      target-to-background ratio. Tracer internalization is also beneficial. For
      oncological imaging, many tracers are available, most originating from regulatory
      peptides, but penetrating peptides are also being developed. Peptides for imaging
      inflammatory and infectious diseases include regulatory peptides, antimicrobial
      peptides and others. In conclusion, for the imaging of oncological, imflammatory
      and infectious diseases, many promising peptides are being developed. The ideal
      peptide probe is characterized by rapid and specific target localization and
      binding with a high tumour-to-background ratio.

PMID- 22388628
TI  - Somatostatin receptor SPECT.
AB  - Somatostatin is a peptide with a broad distribution in the nervous system and
      acts as a neurotransmitter in several organs, having a wide range of mainly
      inhibiting effects, such as the suppression of growth hormone release, as well as
      the inhibition of pancreatic and gastrointestinal hormone release. Five
      somatostatin receptor subtypes have been cloned and demonstrated to have an
      emphasized expression in all human tumours. In particular, type 2 receptors were
      identified as the most frequently represented on the surface of neuroendocrine
      tumour cells, providing the molecular basis for many clinical applications of
      somatostatin analogues. Towards the end of the 1980s, the in vivo demonstration
      of somatostatin receptors on the surface of some tumours raised interest in
      receptor imaging, and indeed the peptide receptor overexpression on tumour cells,
      as compared to normal tissues, constitutes the basis for molecular imaging of
      these tumours. This review intends to illustrate the development of single photon
      emission radiopharmaceuticals for the study of somatostatin receptors and their
      application in diagnostic imaging.

PMID- 22388632
TI  - Radiolabelled peptides in diagnosis and therapy: an introduction.

PMID- 22388631
TI  - Lutetium-labelled peptides for therapy of neuroendocrine tumours.
AB  - Treatment with radiolabelled somatostatin analogues is a promising new tool in
      the management of patients with inoperable or metastasized neuroendocrine
      tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin
      analogues that have been used for peptide receptor radionuclide therapy (PRRT).
      The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very
      encouraging in terms of tumour regression. Dosimetry studies with (177)Lu
      DOTATATE as well as the limited side effects with additional cycles of (177)Lu
      DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also,
      if kidney-protective agents are used, the side effects of this therapy are few
      and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide
      (DOTATOC). Besides objective tumour responses, the median progression-free
      survival is more than 40 months. The patients' self-assessed quality of life
      increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared
      to historical controls, there is a benefit in overall survival of several years
      from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These
      findings compare favourably with the limited number of alternative therapeutic
      approaches. If more widespread use of PRRT can be guaranteed, such therapy may
      well become the therapy of first choice in patients with metastasized or
      inoperable neuroendocrine tumours.

PMID- 22388634
TI  - A randomized comparative 96-week trial of boosted atazanavir versus continued
      boosted protease inhibitor in HIV-1 patients with abdominal adiposity.
AB  - BACKGROUND: Abdominal adiposity in HIV-1 patients initiating antiretroviral
      therapy may be part of a restoration-to-health phenomenon. Lipoatrophy is
      associated with long-term thymidine analogue therapy. Individual protease
      inhibitors (PIs) differ in their effects on lipids and insulin resistance.
      METHODS: A randomized open-label multicentre 96-week trial compared changes in
      fat distribution in patients with suppressed HIV-1 RNA and abdominal adiposity,
      who either continued on their current twice-daily ritonavir-boosted PI (PI/r) or
      switched to once-daily boosted atazanavir (ATV/r). Treatment with two nucleoside
      reverse transcriptase inhibitors was unchanged. Body composition was assessed by
      dual-energy x-ray absorptiometry (DEXA) and abdominal computerized tomography
      (CT) scanning. RESULTS: In total, 201 patients were randomized; 131 switched to
      ATV/r. Viral suppression (<50 copies/ml) was similarly maintained (93% ATV/r
      versus 89% PI/r). Mean changes from baseline in trunk-to-limb fat ratio were
      similar; difference estimates 0.03 (95% CI -0.06, 0.12; P=0.48 at week 48) and
      0.02 (95% CI -0.10, 0.14; P=0.73 at week 96). More patients in the PI/r arm had a
      decrease of >=20% in limb fat from baseline at week 96. Significantly greater
      reductions in proatherogenic lipids occurred following switch to ATV/r. Both
      treatment regimens were generally well-tolerated; the incidence of grade 3-4
      treatment-related clinical adverse events was 34% among ATV/r recipients versus
      4% of PI/r-treated patients. CONCLUSIONS: Switching to ATV/r had no demonstrable
      benefit on abdominal adiposity. Maintenance of efficacy, less limb fat loss and
      marked reduction in proatherogenic lipids was observed with ATV/r compared with
      continuing a PI/r regimen.

PMID- 22388635
TI  - Trajectories and predictors of return to work after traumatic limb injury--a 2
      year follow-up study.
AB  - OBJECTIVES: This study aims to explore the trajectories of return to work (RTW)
      and examine the predictors of different trajectories among workers following
      traumatic limb injury. METHODS: A total of 804 participants were recruited during
      hospital admission for a 2-year prospective study. The RTW outcome was repeatedly
      assessed at 1, 3, 6, 12, 18, and 24 months after the injury. A group-based
      trajectory model (GBTM) was employed to identify trajectories of RTW among the
      participants. Comparisons of group characteristics of different trajectories were
      performed based on a multinomial logistic regression. RESULTS: GBTM identified
      three distinct trajectories of RTW: (i) fast RTW consisted of workers with early
      and stable RTW status from the first month after the injury; (ii) average RTW
      consisted of workers who achieved and remained at a stable RTW status within 6
      months; and (iii) slow RTW consisted of workers who had slow and unsustainable
      RTW status within the 2-year follow-up period. The estimated proportions were
      21.5%, 50.7%, and 27.8%, respectively. Workers with slow and unsustainable RTW
      after injury were found to be older, married, less educated, employed as repair
      personnel/operators/laborers, seriously injured, and depressed; they were also
      found to feel more disturbance in daily life, have lower self-efficacy, and
      believe they experience a poorer quality of life. CONCLUSION: Following traumatic
      limb injury, individual workers showed three distinct RTW trajectories, each of
      which was associated with different categories of biopsychosocial factors. An
      understanding of how different factors contribute to increasing the likelihood of
      RTW for injured workers in each trajectory group should aid policy-making in
      worker-oriented vocational rehabilitation programs.

PMID- 22388636
TI  - Clickable inverse opal: a useful platform for fabrication of stimuli-responsive
      photonic materials.
AB  - Based on azide-containing clickable inverse opal, a strategy for efficiently
      fabricating functional photonic materials was developed. By using three types of
      ethynylated compounds as model molecules, it is found that different functional
      groups can be facilely introduced into the prepared inverse opal via click
      reaction to access various inverse opaline materials.

PMID- 22388637
TI  - Understanding local electrophilicity/nucleophilicity activation through a single
      reactivity difference index.
AB  - A local reactivity difference index R(k) is shown to be able to predict the local
      electrophilic and/or nucleophilic activation within an organic molecule. Together
      with the electrophilic and/or nucleophilic behavior of the center k given by the
      sign, the magnitude of the R(k) index accounts for the extent of the electronic
      activation, a behavior that allows for the use of the R(k) index as a measure of
      the molecular reactivity especially in polar processes.

PMID- 22388638
TI  - Host immune defense against Aspergillus fumigatus: insight from experimental
      systemic (disseminated) infection.
AB  - Model of systemic Aspergillus fumigatus infection induced by intravenous
      application of conidia is suitable for studying important aspects of invasive
      aspergillosis including relationship between infection and mortality,
      dissemination of infection and immune mechanisms involved in host resistance to
      this fungus. Use of this model allows the investigation of both innate and
      adaptive immune response characteristics in resistant/susceptible host, and
      investigating the contribution of genetic background and cytokine gene deficiency
      improves the knowledge of the diversity of mechanisms of immune response to
      Aspergillus infection. Studying of various aspects of systemic aspergillosis
      contributes to development of antifungal drugs.

PMID- 22388639
TI  - Inflammatory and immune mechanisms in contact hypersensitivity (CHS) in rats.
AB  - Contact hypersensitivity (CHS) is a T-cell-mediated skin inflammatory reaction to
      cutaneous exposure to small sensitizing chemicals, haptens. Majority of CHS
      studies were conducted in mice and there is paucity of data in other experimental
      animals. In this review, after a brief survey of murine CHS, hitherto known
      characteristics of CHS in rats were presented including inflammatory and immune
      mechanisms of both sensitization and elicitation phases. Survey of literature of
      rat CHS is presented, with our data concerning the importance of genetic
      background both in the induction and in the expression of reaction to
      dinitrochlorobenzene. The knowledge of CHS in rats, preferred animal in
      immunopharmacological studies, might help development of immunomodulatory
      intervention in contact allergy.

PMID- 22388640
TI  - Functional properties of granulocytes after thermal injury.
AB  - Thermal injury, as well as other forms of severe trauma, induces simultaneous
      hyper- and anti-inflammatory response. While data about decreased number and
      responsiveness of T lymphocytes are largely consistent, reports concerning
      granulocytes following trauma are contradictory. Contrary to the evidence on the
      increased accumulation of granulocytes in the lungs or liver, the results from
      our laboratory demonstrated reduced granulocyte influx in the wound that heals in
      conditions of thermal injury. We also demonstrated evidence that indicates
      impaired signal transduction in granulocytes following thermal injury, as well as
      their divergent response regarding the adhesiveness, oxidative burst and nitric
      oxide production at the wound site.

PMID- 22388641
TI  - Beta cell function: the role of macrophage migration inhibitory factor.
AB  - During evolution, beta cells adapted to a sole aim: the production and stimulus
      dependent secretion of insulin. This acquired specificity was accompanied by a
      loss of protection mechanisms predisposing beta cell to a high vulnerability.
      Among beta cell-damaging molecules, a new one has been identified recently:
      macrophage migration inhibitory factor (MIF). MIF was at first designated as a T
      cell product that inhibits random movement of macrophages. Over the years, the
      number of functions attributed to this protein increased significantly,
      positioning MIF at the top of inflammatory cascade in the combat against
      infection and in immunoinflammatory and autoimmune diseases. This exceptionally
      versatile molecule regulates insulin secretion in physiological conditions, while
      in pathological states it alters beta cell function and induces their apoptosis
      or necrosis and affects beta cell neoplasia.

PMID- 22388642
TI  - Efficacy and safety of BH4 before the age of 4 years in patients with mild
      phenylketonuria.
AB  - BACKGROUND: Sapropterin dihydrochloride, an EMEA-approved synthetic formulation
      of BH4, has been available in Europe since 2009 for PKU patients older than 4
      years, but its use with younger children is allowed in France based on an expert
      recommendation. We report the cases of 15 patients treated under the age of 4
      years and demonstrate the safety and efficacy of this treatment for patients in
      this age group. PATIENTS AND METHOD: We report the use of BH4 in 15 PKU patients
      treated before the age of 4 years. RESULTS: Fifteen patients were enrolled in
      this retrospective study. Mean phenylalaninemia at diagnosis was 542 +/- 164 MUM
      and all patients had mild PKU (maximal phenylalaninemia: 600-1200 MUM). BH4
      responsiveness was assessed using a 24-hour BH4 loading test (20 mg/kg),
      performed during the neonatal period (n = 11) or before 18 months of age (n = 4).
      During the test, these patients exhibited an 80 +/- 12% decrease in
      phenylalaninemia. Long-term BH4 therapy was initiated during the neonatal period
      (n = 7) or at the age of 13 +/- 12 months (n = 8). The median duration of
      treatment was 23 months [min 7; max 80]. BH4 therapy drastically improved dietary
      phenylalanine tolerance (456 +/- 181 vs 1683 +/- 627 mg/day, p < 0.0001) and
      allowed a phenylalanine-free amino acid mixture to be discontinued or not
      introduced in 14 patients. Additionally, in the eight patients treated after a
      few months of diet therapy, BH4 treatment significantly decreased mean
      phenylalaninemia (352 +/- 85 vs 254 +/- 64 MUM, p < 0.05), raised the percentage
      of phenylalaninemia tests within therapeutic targets [120-300 MUM] (35 +/- 25 vs
      64 +/- 16%, p < 0.05), and reduced phenylalaninemia variance (130 +/- 21 vs 93 +/
      27 MUM, p < 0.05). No side effects were reported. CONCLUSION: BH4-therapy is
      efficient and safe before the age of 4 years in mild PKU, BH4-responsive
      patients.

PMID- 22388643
TI  - Immunohistochemical analysis of the ubiquitin-conjugating enzyme UbcH10 in lung
      cancer: a useful tool for diagnosis and therapy.
AB  - The ubiquitin-conjugating enzyme (UbcH10) plays important roles in the regulation
      of cell cycle progression. Recently, UbcH10 expression has been demonstrated in
      several human and experimental tumors, and proteasome inhibitors have been tested
      in trials for pulmonary neoplasms; however, the underlying mechanisms as well as
      the clinicopathological relevance of UbcH10 in the genesis and progression of
      lung cancer remain largely unknown. Therefore, the authors evaluated the
      expression of UbcH10 in human lung cancer and evaluated its possible diagnostic
      and prognostic use. They found that most cases of lung adenocarcinoma, squamous
      cell carcinoma, and large cell and small cell carcinoma were positive for UbcH10.
      The expression levels of UbcH10 progressively increased with decreasing degree of
      tumor differentiation. There was a statistically significant difference of UbcH10
      positivity between grade I/III of lung adenocarcinoma (p=0.013) and squamous cell
      carcinoma (p=0.002). No significant differences were found between histological
      types (p=0.072). In the case of cell blocks prepared from pleural effusions,
      inflammatory and reactive mesothelial elements did not show appreciable UbcH10
      expression, whereas neoplastic cells exhibited clear UbcH10 positivity. The
      results suggest that UbcH10 might represent a new and promising diagnostic and
      prognostic marker in both histologic and cytologic specimens of lung cancer.

PMID- 22388644
TI  - Immunogenicity of biological therapeutics:  from assay to patient.
AB  - PURPOSE OF REVIEW: To give an overview of the current knowledge on assay
      techniques and clinical implications of immunogenicity of biological
      therapeutics. RECENT FINDINGS: Assay techniques for the measurement of
      immunogenicity have improved, expanding the understanding of the immune response
      against biological therapeutics. Knowledge on the clinical effect of
      immunogenicity enables the treatment of patients in a targeted fashion, as a step
      towards personalized medicine. SUMMARY: Biological medications are able to induce
      an antidrug immune response. Immunogenicity impairs clinical response and is
      associated with adverse events. Several confounding factors influence the
      measurement of immunogenicity, including drug interference and background
      problems. Concomitant administration of methotrexate lowers the frequency and
      amount of antibodies formed, whereby the efficacy of biologicals is improved.
      Algorithms for therapeutic drug monitoring could aid in adapting treatment
      strategies in a controlled setting.

PMID- 22388645
TI  - Advances in imaging.
AB  - PURPOSE OF REVIEW: Imaging of inflammatory activity is of increasing importance,
      and among available modalities, ultrasonography and magnetic resonance imaging
      (MRI) seem to be of highest impact. The present review includes recent studies
      describing several aspects of these modalities as well as short descriptions of
      other promising imaging methods in rheumatoid arthritis (RA). RECENT FINDINGS:
      High reliability has been shown for evaluation of ultrasonography still images.
      Recently excellent reliability was found when an atlas was used as reference for
      scoring dynamic images with ultrasonography. The optimal number of joints to
      examine by ultrasonography for follow-up during therapeutic interventions needs
      to be further explored. Use of ultrasonographic guidance for injections has
      showed improved clinical results when compared with blind injections.
      Ultrasonographic pathology, especially power Doppler, was found to be of
      predictive value in patients with arthritis. Cartilage damage is an important
      aspect of structural joint damage in RA, and a reliable assessment system of
      joint space narrowing has been developed for use with conventional MRI, and
      various biochemical MRI techniques are being developed to visualize cartilage
      quality, of which delayed gadolinium-enhanced magnetic resonance imaging of
      cartilage seems to be the most promising method in RA. SUMMARY: Novel imaging
      modalities, especially ultrasonography and MRI, will be of increasing importance
      to visualize joint inflammation and aid in the diagnosis, treatment and follow-up
      of patients with RA.

PMID- 22388646
TI  - Intensive treatment and treatment holiday of TNF-inhibitors in rheumatoid
      arthritis.
AB  - PURPOSE OF REVIEW: Biologics targeting tumor necrosis factor (TNF) has
      revolutionized the treatment of rheumatoid arthritis (RA) and clinical remission
      becomes a realistic treatment goal. After achieving remission, discontinuation of
      TNF inhibitors may become an important issue from viewing points of safety and
      economy. However, there is not well established firm evidence regarding biologic
      free remission. We here document whether 'treatment holiday' of TNF inhibitors is
      possible in RA patients, after maintaining low disease activity by intensive
      treatment with TNF inhibitors. RECENT FINDINGS: From European studies such as
      BeSt and OPTIMA in patients with early RA and Japanese studies such as RRR and
      HONOR in patients with established RA, after reduction of disease activity to
      clinical remission or low disease activity in patients with RA by infliximab or
      adalimumab in combination with methotrexate, some patients could successfully
      remain in clinical remission without TNF inhibitors for 6 months or 1 year and
      without radiologic and functional progression of articular destruction. SUMMARY:
      After maintaining low disease activity by intensive treatment with TNF
      inhibitors, discontinuation of TNF inhibitors without disease flare, joint damage
      progression and functional impairment, treatment holiday, is possible in some RA
      patients.

PMID- 22388647
TI  - [Clinical relevance of a routinely performed magnetic resonance
      cholangiopancreatography (MRCP) prior to cholecystectomy].
AB  - BACKGROUND: A preoperative diagnostic imaging procedure is essential for therapy
      in cholecystolithiasis. According to the S3-Guidelines of the German Society for
      General and Visceral Surgery only an ultrasound scan is needed before a
      cholecystectomy. But an anatomic variant of the bile ducts or choledocholithiasis
      is poorly shown by an ultrasound. Because of this, we performed a magnetic
      resonance cholangiopancreatography (MRCP) routinely. This study was designed to
      show if the MRCP changed the treatment plan or changed the operation method.
      Furthermore, the sensitivity and specificity concerning abnormalities of the
      cystic duct, accessory bile ducts and choledocholithiasis should be determined.
      PATIENTS AND METHODS: During the time between January 1st 2005 and September 30th
      2009 541 patients were included in this retrospective study. RESULTS: Among the
      541 cases 98 pathologies were found. These included 51 choledocholithiasis, 20
      accessory bile ducts and 13 abnormal cystic ducts. In 29 of the 51 cases of
      choledocholithiasis a therapeutic splitting was performed only because of the
      MRCP. In 22 cases the diagnosis was also possible because of the basic diagnostic
      procedures like ultrasound, laboratory tests and clinical appearance. So the
      diagnostic aimprovement due to the MRCP is 5.3 %. Four of the 20 accessory bile
      ducts and 6 of the abnormal cystic ducts were found during the subsequent
      operation. The sensitivity concerning the anatomic variants is very low (38.5 %
      concerning the accessory bile ducts and 50 % for the abnormal cystic ducts). But
      the sensitivity in detecting a choledocholithiasis is very high (94.7 %). There
      was no evidence in our study that MRCP prevented any complications. The operation
      method was not changed in any case because of the MRCP result. CONCLUSION: A
      routinely performed preoperative MRCP cannot be recommended.

PMID- 22388648
TI  - [Isolated traumatic duodenal perforation after a bicycle accident].

PMID- 22388649
TI  - [Finding-specific minimally invasive approach for acute radiation-induced
      cholecystitis after (90)Y-radioembolisation of intrahepatic metastases].

PMID- 22388650
TI  - [20th Congress of the Central Germany Society for Gastroeneterology (CGSG) -
      Cooperation between gastroenterology and visceral surgery in visceral medicine].

PMID- 22388653
TI  - Morphine preconditioning protects against LPS-induced neuroinflammation and
      memory deficit.
AB  - Recent studies show that morphine possesses protective preconditioning effects in
      different ischemia/reperfusion models. However, there is very little information
      about the antineuroinflammatory role of morphine and its protective effect
      against memory deficit. In the present study, we evaluated the role of morphine
      preconditioning in a model of mild neuroinflammation induced by intraperitoneal
      lipopolysaccharide (LPS) injection (1 mg/kg). Rats were trained on passive
      avoidance apparatus and challenged with LPS 20 h later. Four hours after LPS,
      rats were subjected to passive avoidance testing and then for the assessments of
      inflammatory and apoptotic cell death mediators in the hippocampus. LPS
      significantly increased the nuclear NF-kappaB and expression of COX-2, IL-1beta,
      and TNF-alpha, augmented the activity of caspase-3 and PARP cleavage, and in
      parallel shortened the latencies to enter the dark compartment. Although morphine
      injection in a noninflammatory context was able to induce a neuroinflammatory
      response and memory loss, morphine preconditioning at the dose of 4 mg/kg
      significantly prevented the LPS-induced neuroinflammation and memory deficit.
      Morphine preconditioning was abolished by naloxone and, therefore, is dependent
      on opioid receptors. These results suggest that acute morphine injection, in
      spite of the induction of a neuroinflammatory response and amnesia per se, exerts
      an antineuroinflammatory role and protects from cell death and memory deficit in
      an inflammatory context.

PMID- 22388654
TI  - Chromogranin A and derived peptides in health and disease.
AB  - Chromogranin A (CgA) is a member of the granins, a family of acidic proteins
      found in abundance in (neuro)endocrine cells (e.g., in chromaffin cells) and in
      some tumors. Like other granins, CgA has a granulogenic role in secretory granule
      biogenesis and is stored in these organelles. CgA is partially processed
      differentially in various cell types to yield biologically active peptides, such
      as vasostatin, pancreastatin, catestatin, and serpinins. In this review, we
      describe the roles of CgA and several of its derived peptides. CgA, which is
      elevated in the blood of cancer patients, inhibits angiogenesis and exerts
      protective effects on the endothelial barrier function in tumors, thus affecting
      response to chemotherapy. Recent studies indicate that the serpinins promote cell
      survival and myocardial contractility and relaxation. Other peptides such as
      pancreastatin were found to have significant effects on inhibition of glucose
      stimulated insulin secretion and glucose up-take, induction of glycogenolysis in
      hepatocytes, and inhibition of lipogenesis. In contrast, catestatin has opposite
      effects to that of pancreastatin in glucose metabolism and lipogenesis.
      Catestatin appears to also play a significant role in cardiac function, blood
      pressure regulation, and mutations in the catestatin domain of the CgA gene are
      associated with hypertension in humans.

PMID- 22388655
TI  - Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse
      uterus and vagina.
AB  - Both the uterus and vagina develop from the Mullerian duct but are quite distinct
      in morphology and function. To investigate factors controlling epithelial
      differentiation and cell proliferation in neonatal uterus and vagina, we focused
      on Hedgehog (HH) signaling. In neonatal mice, Sonic hh (Shh) was localized in the
      vaginal epithelium and Indian hh (Ihh) was slightly expressed in the uterus and
      vagina, whereas all Glioma-associated oncogene homolog (Gli) genes were mainly
      expressed in the stroma. The expression of target genes of HH signaling was high
      in the neonatal vagina and in the uterus, it increased with growth. Thus, in
      neonatal mice, Shh in the vaginal epithelium and Ihh in the uterus and vagina
      activated HH signaling in the stroma. Tissue recombinants showed that vaginal Shh
      expression was inhibited by the vaginal stroma and uterine Ihh expression was
      stimulated by the uterine stroma. Addition of a HH signaling inhibitor decreased
      epithelial cell proliferation in organ-cultured uterus and vagina and increased
      stromal cell proliferation in organ-cultured uterus. However, it did not affect
      epithelial differentiation or the expression of growth factors in organ-cultured
      uterus and vagina. Thus, activated HH signaling stimulates epithelial cell
      proliferation in neonatal uterus and vagina but inhibits stromal cell
      proliferation in neonatal uterus.

PMID- 22388656
TI  - Cellular distribution of NKCC2 in the gastric mucosa and its response to short
      term osmotic shock.
AB  - The Na(+)-K(+)-2Cl(-) cotransporter-2 (NKCC2) has long been recognized as a
      "kidney-specific" transporter and is important in salt reabsorption. NKCC2 has
      been found in the gastric mucosa; however, its cellular distribution and function
      remain obscure. The present study characterized the distribution pattern of NKCC2
      in mammalian gastric mucosa and investigated its response to osmotic challenge.
      Reverse transcription with the polymerase chain reaction, Western blot and
      immunofluorescence were used to determine NKCC2 expression and localization. The
      effect of osmotic shock on NKCC2 expression was studied in isolated gastric
      mucosa with variable osmolarity treatment. Results from all of the above studies
      were compared with those of NKCC1. Our data indicated that NKCC1 and NKCC2 were
      expressed in the gastric mucosa of rat, mouse and human. The mRNA transcripts and
      proteins for NKCC1 and NKCC2 were broadly expressed in the rat gastric mucosa. In
      rat and mouse, NKCC1 was largely confined to the lower part of the oxyntic and
      pyloric gland areas, whereas NKCC2 extended throughout the gastric glands. NKCC1
      immunoreactivity was strongly expressed in the parietal and chief cells but was
      weaker in the mucous cells. NKCC2 was abundantly located in the parietal and
      mucous cells but faintly distributed in the chief cells. Hypertonic treatment
      increased the protein level of NKCC1 and caused evident membrane translocation.
      In contrast, NKCC2 was significantly downregulated and no obvious membrane
      translocation was observed. Thus, NKCC2 displayed a more ubiquitous distribution
      in the gastric mucosa and might work coordinately with NKCC1 to maintain cell
      volume homeostasis under hypertonic conditions.

PMID- 22388657
TI  - Neural stem cells for spinal cord repair.
AB  - Spinal cord injury (SCI) causes the irreversible loss of spinal cord parenchyma
      including astroglia, oligodendroglia and neurons. In particular, severe injuries
      can lead to an almost complete neural cell loss at the lesion site and structural
      and functional recovery might only be accomplished by appropriate cell and tissue
      replacement. Stem cells have the capacity to differentiate into all relevant
      neural cell types necessary to replace degenerated spinal cord tissue and can now
      be obtained from virtually any stage of development. Within the last two decades,
      many in vivo studies in small animal models of SCI have demonstrated that stem
      cell transplantation can promote morphological and, in some cases, functional
      recovery via various mechanisms including remyelination, axon growth and
      regeneration, or neuronal replacement. However, only two well-documented neural
      stem-cell-based transplantation strategies have moved to phase I clinical trials
      to date. This review aims to provide an overview about the current status of
      preclinical and clinical neural stem cell transplantation and discusses future
      perspectives in the field.

PMID- 22388659
TI  - Spin caloritronics: electron spins blow hot and cold.

PMID- 22388660
TI  - Nanobiotechnology: checking out the insides of cells.

PMID- 22388661
TI  - Influence of dipole-dipole correlations on the stability of the biaxial nematic
      phase in the model bent-core liquid crystal.
AB  - A molecular theory of biaxial nematic ordering in the system of bent-core
      molecules has been developed in  the two-particle cluster approximation which
      enables one to take into account short-range polar correlations determined by
      both electrostatic dipole-dipole interaction and polar molecular shape. All
      orientational order parameters and short-range correlation functions are
      calculated numerically as functions of temperature in the uniaxial and in the
      biaxial nematic phases, and the results are compared with the ones obtained in
      the mean-field approximation and in the cluster approximation but without taking
      into consideration the dipole-dipole interaction. It is shown that short-range
      polar correlations and, in particular, the dipole-dipole correlations
      dramatically increase the temperature of the transition into the biaxial nematic
      phase and enhancing its stability range. The results are also very sensitive to
      the value of the opening angle of a model bent-core molecule.

PMID- 22388662
TI  - DNA electrophoresis in a nanofence array.
AB  - We present the design and implementation of an oxidized silicon "nanofence array"
      for long DNA electrophoresis. The device consists of a periodic array of post
      filled regions (the nanofences) alternating with empty channel regions. Even in
      this prototype version, the nanofence array provides the resolving power of a
      hexagonal nanopost array without requiring any direct-write nanopatterning steps
      such as electron-beam lithography. Through detailed single molecule
      investigations, we demonstrate that the origin of the resolving power of the
      nanofence array is not a reduction in band broadening, which might be expected
      from the theories for DNA electrophoresis in post arrays. Rather, the enhanced
      stretching of the hooked DNA by the uniform electric field between nanofences
      increases the efficiency of the collisions.

PMID- 22388664
TI  - Active surveillance in prostate cancer:  patient selection and triggers for
      intervention.
AB  - PURPOSE OF REVIEW: The long-term safety and effectiveness of active surveillance
      depends on our ability to select appropriate patients and trigger delayed
      treatment in those who need it, whereas avoiding intervention in those who do
      not. In this review, we will consider how recent advances have influenced patient
      selection for active surveillance and review the range of different intervention
      triggers that have been proposed. RECENT FINDINGS: Several large surveillance
      cohort studies have been reported recently showing excellent medium-term outcomes
      in well selected patients, with approximately a third of patients going on to
      have deferred treatment. Debate continues on the most appropriate eligibility
      criteria for active surveillance and what triggers for intervention should be
      used. There is growing interest in the role of transperineal template biopsies
      and multiparametric MRI, both for patient selection and in identifying triggers
      for intervention. SUMMARY: Active surveillance is a well tolerated treatment
      option in well selected groups of patients. There is no 'one size fits all' set
      of criteria for patient selection or triggers for intervention but decisions can
      be guided by information from histology, prostate-specific antigen kinetics and
      imaging.

PMID- 22388665
TI  - MRI and surveillance.
AB  - PURPOSE OF REVIEW: In this review, we summarize the recent advances in modern
      imaging, particularly multiparametric (mp) MRI and its role in the selection and
      monitoring of patients on active surveillance. RECENT FINDINGS: Current
      diagnostic pathway has some limitations in selecting patients with insignificant
      prostate cancer for active surveillance. Hence, percentage of men under active
      surveillance for insignificant prostate cancer and reclassified as significant
      cancer at 2 years is 20-30%. It is mainly because of anterior cancer
      underdiagnosis by systematic posterior biopsies. mp-MRI is accurate for
      significant cancer detection and staging, including anterior cancers, which
      represent 20% of cancers in an unselected population of men with suspicious
      prostate-specific antigen elevation. One way to reduce the risk of
      underestimation is to target the needle on significant cancer identified at
      prebiopsy anatomical and functional imaging, so that detection and personalized
      risk stratification can be improved. MRI reveals greater volume of cancers and
      higher grade than systematic 12-core biopsies. MRI 95% negative predictive value
      has the potential to avoid biopsy series for monitoring patients under active
      surveillance. SUMMARY: Upon confirmation of these results, MRI may be used to
      better select patients for active surveillance inclusion. Incorporation of mp-MRI
      into active surveillance selection criterias for patients with low-risk prostate
      cancer can reduce the number of patients reclassified at subsequent biopsies
      because of better initial prognosis evaluation. In addition to additional cost,
      MRI requires a highly skilled team to obtain information adequate to drive
      clinical decisions.

PMID- 22388667
TI  - Adolescent bariatric surgery.
AB  - Overall it is clear that bariatric surgical intervention in appropriately
      selected adolescents is effective at both adequate weight loss and resolution of
      weight related co-morbidities in the short and medium term. Long-term results are
      being conducted currently to assess durability of bariatric surgical
      interventions. We believe that adolescents undergoing bariatric evaluation have
      unique needs and until more long-term data are available, the indications for
      surgery should be stricter than those used in adults. All of the bariatric
      procedures discussed must be performed in the background of positive behavioral
      modifications over a period of time. If lifestyle modification fails, these
      adolescents can gain weight by overcoming the physiologic effects of the surgery
      as they eat high calorie foods at very frequent intervals. Finally, close
      postoperative follow-up is required with active management of weight loss/gain,
      co-morbidities, and postoperative complications should they occur.

PMID- 22388666
TI  - Economic analysis of active surveillance for localized prostate cancer.
AB  - PURPOSE OF REVIEW: Active surveillance is gaining wider acceptance in the
      urologic community as an effective treatment option for patients with low-risk
      prostate cancer. The purpose of this review is to analyze the economics of active
      surveillance in comparison with other therapies. RECENT FINDINGS: Evaluating the
      economics of active surveillance in patients with low-risk prostate cancer is
      constrained by a prolonged natural history of disease. Recent cost model studies
      using hypothetical patients with low-risk prostate cancer showed that the
      estimated direct cost of active surveillance over long term was the lowest
      compared with direct costs of immediate treatment with radical prostatectomy,
      external beam radiation therapy, primary androgen deprivation therapy or
      brachytherapy. Active surveillance is associated with more quality-adjusted life
      years than immediate therapies with similar or lower lifetime costs. Physician
      reimbursement for active surveillance exceeded that from upfront radical
      prostatectomy after 3-5 years of follow-up and may be an important driving factor
      for physicians to practice active surveillance. SUMMARY: Active surveillance
      appears to reduce prostate cancer healthcare expenditure by reducing the number
      of costly therapies. Results from clinical trials will allow the measurement of
      the true economic value of active surveillance in the future.

PMID- 22388668
TI  - Complications of Roux-en-Y gastric bypass and sleeve gastrectomy.
AB  - Roux-en-Y gastric bypass and sleeve gastrectomy are two of the most common
      bariatric procedures performed in 2011. Although the complication rates
      associated with these procedures are low, the consequences of these complications
      are significant and can be associated with high morbidity and mortality. Timely
      diagnosis and proper management of these complications are extremely important.
      The most commonly used radiologic studies in bariatric surgery are the upper GI
      contrast study and the CT scan, which are used to rule out leak, obstruction,
      perforation, anastomotic stricture, or pouch dilatation. As with all imaging
      studies, a negative result should not override strong clinical suspicion of a
      complication.

PMID- 22388669
TI  - Macular thickness and aging in retinitis pigmentosa.
AB  - PURPOSE: This study was designed to analyze macular tomography in patients of
      different ages with retinitis pigmentosa (RP) and correlate their visual function
      with macular thickness, which was measured by optical coherence tomography.
      METHODS: In all, 75 RP patients and 75 controls were stratified into three age
      groups and macular thickness was measured by optical coherence tomography. The
      tomography was subdivided into three circular zones, four quadrants, and nine
      areas for analysis. Ophthalmic examinations, which involved ophthalmoscopic
      examinations, dark adaptation tests, visual acuities, visual field examinations,
      electrooculography, and color sense discrimination tests, were performed.
      RESULTS: Macular thickness of the RP patients decreased in the middle age group
      (45- to 55-year old), whereas the oldest group showed an increased thickness. The
      thickness of the outer inferior area remained virtually unchanged, whereas the
      thickness of the inner temporal area showed the most fluctuation with age. In
      terms of circular sections, the most dramatic changes in macular thickness were
      observed in the fovea, and the aging effect decreased outward to the outer ring.
      Furthermore, the thickness of the fovea was more important than the thickness of
      the inner ring and the outer ring for electrooculography, visual acuity, and
      color sense discrimination in RP patients. CONCLUSIONS: In middle age RP
      patients, the macular thickness decreased, whereas an increased thickness was
      observed in patients older than 55 years. In addition, the inner temporal area
      was the most fragile, and the outer inferior area was the least affected in
      patients with RP.

PMID- 22388670
TI  - Impact of tear film components on lysozyme deposition to contact lenses.
AB  - PURPOSE: To investigate the impact of lactoferrin and lipids on the kinetic
      deposition of lysozyme on silicone and conventional hydrogel lenses, using a
      complex artificial tear solution (ATS). METHODS: Two silicone hydrogel lenses
      (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two
      conventional hydrogel lenses (ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A)
      were investigated. Lenses were incubated in four different solutions: a complex
      ATS consisting of various salts, lipids, proteins, and mucins, an ATS without
      lactoferrin (ATS w/o Lac), an ATS without lipids (ATS w/o Lip), and an ATS
      without lactoferrin and lipids (ATS w/o Lac & Lip), each containing 2%
      radiolabeled (125I) lysozyme (1.9 mg/ml). After each time point (4, 12 h and 1,
      2, 3, 5, 7, 14, 21, 28 days), the amount of lysozyme per lens was quantified.
      RESULTS: After 28 days, lotrafilcon B lenses incubated in ATS deposited
      significantly less lysozyme (9.7 +/- 1.4 MUg) than when incubated in solutions
      not containing lactoferrin and lipids (more than 11.8 MUg) (p < 0.001). Lysozyme
      uptake to senofilcon A lenses was higher in ATS w/o Lip (5.3 +/- 0.1 MUg)
      compared with other solutions (less than 3.9 MUg) (p < 0.001). Etafilcon A lenses
      deposited the most lysozyme in all four solutions compared with the rest of the
      lens types (p < 0.001). For etafilcon A lenses, less lysozyme was deposited when
      incubated in ATS w/o Lip (588.6 +/- 0.4 MUg) compared with the other solutions
      (more than 642.6 MUg) (p < 0.001). Omafilcon A lenses in ATS w/o Lac accumulated
      significantly less lysozyme (12.8 +/- 1.0 MUg) compared with the other solutions
      (more than 14.2 MUg) (p < 0.001). CONCLUSIONS: An ATS containing lactoferrin and
      lipids impacts lysozyme deposition on both silicone and conventional hydrogel
      contact lenses. When performing in vitro experiments to study protein deposition
      on contact lenses, more complex models should be used to better mimic the human
      tear film.

PMID- 22388671
TI  - Mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) followed by autologous
      stem cell transplantation for patients with chemosensitive aggressive non-Hodgkin
      lymphoma.
AB  - Patients with chemosensitive aggressive non-Hodgkin lymphoma (NHL) could benefit
      from high-dose chemotherapy (HDC) followed by autologous stem cell
      transplantation (auto-SCT). We report clinical outcomes of HDC using a novel
      regimen consisting of mitoxantrone, etoposide, cytarabine, and melphalan (NEAM)
      with auto-SCT. A total of 69 patients were consecutively enrolled. Median age was
      42 years (range, 20-66 years). Median event-free survival (EFS) was 17.9 months.
      Median overall survival (OS) has not been reached yet and estimated 2-year OS was
      64.2%. Among patients with measurable lesions, response rate was 79.5%. Median
      time to recovery of neutrophil (>500 mL) and platelet (gt;20,000 mL) was 12.5 and
      13.5 days, respectively. Febrile neutropenia developed in 61 patients (88.4%).
      Grades 3 or 4 hepatic toxicity developed in 7 patients (10.1%), Grades 3 or 4
      renal toxicity in 2 patients (2.9%), and Grade 3 or 4 cardiac toxicity in 2
      patients (2.9%). Transplant-related mortality (TRM) developed in two patients
      (2.9%). Multiple prior treatments before transplantation, auxiliary bone marrow
      harvest for stem cell collection, and high serum lactate dehydrogenase level were
      related to unfavorable treatment outcomes. In conclusion, NEAM conditioning with
      auto-SCT demonstrated considerable efficacy with modest toxicity in patients with
      chemosensitive aggressive NHL.

PMID- 22388672
TI  - Individual predictions based on nonlinear mixed modeling: application to prenatal
      twin growth.
AB  - The assessment of growth during fetal life and childhood commonly relies upon
      cross'sectional reference ranges or centiles. However, individual sequential
      predictions may help the timewise assessment of a growth process. In twin
      pregnancies for example, which are at risk of growth restriction, such
      predictions may improve the detection of abnormal trajectories. In this article,
      we present a simple forecasting method, assuming that a given normal individual
      behaves in the same way as a reference population. We consider, as a prediction
      in a given individual, the forecast of a future observation conditional to any
      previous observation and a set of population parameters obtained by nonlinear
      mixed modeling in a reference population. We suggest an estimator for this
      prediction without resorting to linear approximation and show that it enjoys
      interesting asymptotics when the amount of observations increases over time. We
      use two independent real datasets of twin pregnancies with normal growth and
      outcome to illustrate the application of such predictions in prenatal growth. We
      consider the first dataset as a reference dataset and model it using a two'level
      nonlinear model. We perform illustration and validation of predictions on the
      second dataset.

PMID- 22388673
TI  - Canine-assisted therapy in military medicine. The early years.

PMID- 22388674
TI  - Policy initiatives for the use of canines in Army medicine.

PMID- 22388675
TI  - Definitions of animals used in healthcare settings.

PMID- 22388676
TI  - Historical perspectives of the human-animal bond within the Department of
      Defense.

PMID- 22388677
TI  - Dogs and human health/mental health: from the pleasure of their company to the
      benefits of their assistance.

PMID- 22388678
TI  - Research on benefits of canine-assisted therapy for adults in nonmilitary
      settings.
AB  - Research has examined the physiological and psychosocial impact of animal
      assisted activities (AAA) and animal-assisted therapy (AAT). The current review
      article summarizes the benefits of AAA and AAT for hospitalized patients with
      medical disorders, psychiatric patients, and residents of nursing homes and long
      term care facilities. The literature regarding inclusion of animals in business
      and organizational settings is also reviewed. Although there is clear evidence of
      improved physical and psychological health from AAA and AAT in the civilian
      population, there is a dearth of published findings of the evaluation of such
      benefits for military personnel.

PMID- 22388679
TI  - The effects of animal-assisted therapy on wounded warriors in an Occupational
      Therapy Life Skills program.
AB  - Animal-assisted therapy (AAT) has gained much attention in civilian and military
      health care. Evidence supports its benefits with varied populations with diseases
      and disabilities, but no research has been done with injured or ill service
      members. This pretest, posttest nonrandomized control group study evaluated the
      effects of AAT on Warriors in transition (N=24) attending an Occupational Therapy
      Life Skills program with the long-term goal of improving their successful
      reintegration. Although significant differences were not found between the groups
      on most measures, anecdotal reports by participants and observers indicate that
      participants eagerly anticipated being with the therapy dogs, expressed pleasure
      and satisfaction with the experience, and regretted seeing it end. There were
      significant correlations between mood, stress, resilience, fatigue, and function
      at various measurement points. This is the first study to formally assess the
      benefits of AAT with wounded service members in garrison. Suggestions for future
      research are provided.

PMID- 22388680
TI  - Training the combat and operational stress control dog: an innovative modality
      for behavioral health.
AB  - Combat and operational stress control (COSC) dogs represent a new category of
      military working dog. America's VetDogs, a nongovernmental, not-for-profit
      organization, trains and provides therapy dogs to work with the US Army's combat
      and operational stress control teams deployed to Afghanistan or Iraq. By taking
      the therapy/service dog concept to the next level, these dogs have become an
      important modality in the Army's initiative to safeguard Soldiers' behavioral
      health while deployed, allowing COSC unit members to break down stigmas that are
      still present when dealing with behavioral health issues. The training process
      begins by choosing a pool of dogs, exposing them to different sensory experiences
      over several months, and training the primary and secondary handlers who will be
      responsible for the dogs while deployed in theater. After their deployment ends,
      the dogs are retrained by America's VetDogs to further serve in military or
      Veterans Administration medical centers as physical, occupational, or behavioral
      therapy dogs.

PMID- 22388681
TI  - Occupational therapists as dog handlers: the collective experience with animal
      assisted therapy in Iraq.
AB  - The first pair of US Army animal-assisted therapy (AAT) dogs deployed to Iraq in
      December 2007 with the 85th Medical Detachment Combat and Operational Stress
      Control unit. As of this writing, 6 dogs have deployed to Iraq and Afghanistan,
      offering Soldiers a small reminder of home. Army occupational therapists led the
      way in this endeavor as primary handlers; the path has been rocky but ultimately
      rewarding. This article depicts how occupational therapists used AAT and animal
      assisted activities to help Soldiers cope with the stressors of living in a
      deployed environment. Challenges and lessons-learned, including anecdotal
      examples, are discussed.

PMID- 22388682
TI  - Crossing the berm: an occupational therapist's perspective on animal-assisted
      therapy in a deployed environment.

PMID- 22388683
TI  - Rehabilitative canine interactions at the Walter Reed National Military Medical
      Center.

PMID- 22388684
TI  - Canines for combat veterans: the National Education for Assistance Dog Services.

PMID- 22388685
TI  - Service dog training program for treatment of posttraumatic stress in service
      members.
AB  - In July 2008, social worker and certified service dog trainer Rick Yount created
      the first Warrior dog-training program designed to be a safe, effective,
      nonpharmaceutical intervention to treat the symptoms of posttraumatic stress
      disorder (PTSD) and traumatic brain injury in Veterans and service members
      undergoing treatment at a large Veterans Administration residential treatment
      facility. In 2009, Yount was asked to establish the program at a prominent
      Department of Defense medical center. In October 2010, Yount was invited to
      create a service dog training program to support the research and treatment
      mission at the new National Intrepid Center of Excellence (NICoE), in Bethesda,
      Maryland. This program, now being offered through the nonprofit foundation
      Warrior Canine Connection, continues to produce anecdotal evidence that training
      service dogs reduces the PTSD symptoms of Warrior-trainers and that the presence
      of the dogs enhances the sense of wellness in the NICoE staff and the families of
      our Wounded Warriors. Under the research leadership of the NICoE, the Warrior
      Canine Connection research team plans to systematically investigate the
      physiological, psychological, and behavioral benefits of this program.

PMID- 22388686
TI  - Reclaiming identity through service to dogs in need.
AB  - Dog Tags is an animal-assisted therapy offered by the Washington Humane Society
      (WHS) in partnership with the Walter Reed National Military Medical Center
      (WRNMMC). The program is open to all ranks of enlisted service members using
      WRNMMC services. Dog Tags is a 3-tiered certificate program allowing Soldiers,
      recovering at WRNMMC, to learn and apply progressively complex and challenging
      elements of canine positive reinforcement training to dogs awaiting adoption at
      the WHS. Although each tier is a self-contained and complete curriculum,
      subsequent tiers build on the skills and knowledge acquired in the previous
      one(s). Dog Tags Warrior/trainers work with fully-screened (health and
      temperament) shelter dogs to provide these dogs with mental stimulation,
      environmental enrichment, and socialization that are vital to their successful
      adoption and integration into new homes. The Soldiers also benefit because they
      develop new skills, build positive bonds with the dogs, and continue to serve
      their community.

PMID- 22388687
TI  - Therapy dogs and stress management assistance during disasters.

PMID- 22388691
TI  - Dispersal and microsite limitation in Australian old fields.
AB  - The recovery of native communities after cultivation may be constrained by (a)
      the failure of species to reach a site or (b) their failure to survive once
      there. Although seed addition is a common method to test for seed versus
      microsite limitation, most studies do not follow populations beyond seedling
      establishment, nor do they measure seed dispersal. We examined dispersal across
      native grassland/old field boundaries and investigated the relative importance of
      seed and microsite limitation across multiple life-history stages and
      generations. Seed trapping showed little movement of native seeds into old fields
      and that most species had extremely localized dispersal. Consequently, there was
      no pattern of seed density with distance from boundaries, and similarity between
      the seed rain and standing vegetation was moderate to high. Seed addition showed
      that two annual species were able to establish in all, and flower in most,
      subplots in the first year, and that seedling establishment increased with sowing
      density, consistent with seed limitation. However, the relative importance of
      microsite limitation increased over the lifespans of the species. Density
      dependence reduced the number of flowering plants, resulting in a large decline
      in seedling density in the following generation. This decline continued so that
      the initial positive effect of sowing density on seedling numbers disappeared by
      the fourth generation and hence the persistence of populations is uncertain.
      Thus, by monitoring seed dispersal and following experimental populations beyond
      seedling establishment, we showed that dispersal limits species distributions,
      but microsite plays an important role in limiting population growth and
      persistence.

PMID- 22388689
TI  - Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform
      for future biorefineries.
AB  - Metabolic engineering is the enabling science of development of efficient cell
      factories for the production of fuels, chemicals, pharmaceuticals, and food
      ingredients through microbial fermentations. The yeast Saccharomyces cerevisiae
      is a key cell factory already used for the production of a wide range of
      industrial products, and here we review ongoing work, particularly in industry,
      on using this organism for the production of butanol, which can be used as
      biofuel, and isoprenoids, which can find a wide range of applications including
      as pharmaceuticals and as biodiesel. We also look into how engineering of yeast
      can lead to improved uptake of sugars that are present in biomass hydrolyzates,
      and hereby allow for utilization of biomass as feedstock in the production of
      fuels and chemicals employing S. cerevisiae. Finally, we discuss the perspectives
      of how technologies from systems biology and synthetic biology can be used to
      advance metabolic engineering of yeast.

PMID- 22388692
TI  - Importance of highly selective LC-MS/MS analysis for the accurate quantification
      of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.
AB  - The antiestrogenic effect of tamoxifen is mainly attributable to the active
      metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be
      concentration-dependent and therefore quantitative analysis of tamoxifen and
      metabolites for clinical studies and therapeutic drug monitoring is increasing.
      We investigated the large discrepancies in reported mean endoxifen and 4
      hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to
      analyse a set of 75 serum samples from patients treated with tamoxifen. The
      method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen
      and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and
      fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A,
      1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3
      overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We
      emphasize the use of highly selective LC-MS/MS methods for the quantification of
      tamoxifen and its metabolites in biological samples.

PMID- 22388688
TI  - Regenerating functional heart tissue for myocardial repair.
AB  - Heart disease is one of the leading causes of death worldwide and the number of
      patients with the disease is likely to grow with the continual decline in health
      for most of the developed world. Heart transplantation is one of the only
      treatment options for heart failure due to an acute myocardial infarction, but
      limited donor supply and organ rejection limit its widespread use. Cellular
      cardiomyoplasty, or cellular implantation, combined with various tissue
      engineering methods aims to regenerate functional heart tissue. This review
      highlights the numerous cell sources that have been used to regenerate the heart
      as well as cover the wide range of tissue-engineering strategies that have been
      devised to optimize the delivery of these cells. It will probably be a long time
      before an effective regenerative therapy can make a serious impact at the
      bedside.

PMID- 22388693
TI  - Tyrosine phosphorylation and bacterial virulence.
AB  - Protein phosphorylation on tyrosine has emerged as a key device in the control of
      numerous cellular functions in bacteria. In this article, we review the structure
      and function of bacterial tyrosine kinases and phosphatases. Phosphorylation is
      catalyzed by autophosphorylating adenosine triphosphate-dependent enzymes
      (bacterial tyrosine (BY) kinases) that are characterized by the presence of
      Walker motifs. The reverse reaction is catalyzed by three classes of enzymes: the
      eukaryotic-like phosphatases (PTPs) and dual-specific phosphatases; the low
      molecular weight protein-tyrosine phosphatases (LMW-PTPs); and the polymerase
      histidinol phosphatases (PHP). Many BY kinases and tyrosine phosphatases can
      utilize host cell proteins as substrates, thereby contributing to bacterial
      pathogenicity. Bacterial tyrosine phosphorylation/dephosphorylation is also
      involved in biofilm formation and community development. The Porphyromonas
      gingivalis tyrosine phosphatase Ltp1 is involved in a restraint pathway that
      regulates heterotypic community development with Streptococcus gordonii. Ltp1 is
      upregulated by contact with S. gordonii and Ltp1 activity controls adhesin
      expression and levels of the interspecies signal AI-2.

PMID- 22388695
TI  - Validation of the Brazilian version of Chronic Liver Disease Questionnaire.
AB  - PURPOSE: The aim of this study was to validate the Chronic Liver Disease
      Questionnaire (CLDQ) for use in Brazilian population. METHOD: A total of 200
      patients with chronic liver disease and varying disease severity answered a socio
      demographic questionnaire, t CLDQ, and the Medical Outcome Study Short Form 36
      (SF-36). Patients returned in 1-15 days to answer CLDQ again. The Cronbach's
      alpha of the total CLDQ score was 0.95 and fluctuated between 0.69 and 0.83 in
      its six domains. RESULTS: The intra-class correlation between total CLDQ scores
      in two evaluations was 0.97 and in all domains was >0.93. CLDQ was moderately
      correlated with the SF-36, 0.63 (total CLDQ vs. vitality, SF-36), 0.62 (CLDQ and
      mental health, SF-36), 0.62 (preoccupation, CLDQ, vs. General Health, SF-36),
      0.59 (fatigue, CLDQ, vs. vitality, SF-36), 0.59 (activity, CLDQ, vs. vitality, SF
      36), and 0.59 (fatigue, CLDQ, vs. mental health, SF-36). The highest scores were
      found in non-cirrhotic group. Child A patients had higher average scores than
      Child B and C groups in all domains, while patients with MELD <15 scored higher
      than patients with MELD >=15. CONCLUSION: CLDQ-BR was validated in Brazilian
      population and was appropriate for use in patients with liver disease of
      different etiologies and degrees of severity.

PMID- 22388694
TI  - Autonomic and cardiovascular effects of pentobarbital anesthesia during
      trigeminal stimulation in cats.
AB  - Stimulation of the trigeminal nerve can elicit various cardiovascular and
      autonomic responses; however, the effects of anesthesia with pentobarbital sodium
      on these responses are unclear. Pentobarbital sodium was infused intravenously at
      a nominal rate and the lingual nerve was electrically stimulated at each infusion
      rate. Increases in systolic blood pressure (SBP) and heart rate (HR) were evoked
      by lingual nerve stimulation at an infusion rate between 5 and 7 mg.kg(-1).h(-1).
      This response was associated with an increase in the low-frequency band of SBP
      variability (SBP-LF). As the infusion rate increased to 10 mg.kg(-1).h(-1) or
      more, decreases in SBP and HR were observed. This response was associated with
      the reduction of SBP-LF. In conclusion, lingual nerve stimulation has both
      sympathomimetic and sympathoinhibitory effects, depending on the depth of
      pentobarbital anesthesia. The reaction pattern seems to be closely related to the
      autonomic balance produced by pentobarbital anesthesia.

PMID- 22388696
TI  - Rheumatoid arthritis: RA risk variants in the groove.

PMID- 22388697
TI  - Therapy: Silencing inhibitors of bone formation.

PMID- 22388698
TI  - Translational phases of evidence in a prognostic biomarker: a systematic review
      and meta-analysis of natriuretic peptides and the prognosis of stable coronary
      disease.
AB  - CONTEXT: Translational phases of study are important in evaluating whether a
      prognostic biomarker is likely to have impact on clinical practice but systematic
      evaluations of such evidence are lacking. OBJECTIVE: To systematically evaluate
      the clinical usefulness of the published literature on the association of
      natriuretic peptides (NP) and prognosis in stable coronary disease. DATA SOURCES:
      MEDLINE and EMBASE until the end of July 2009, without restrictions. STUDY
      SELECTION: Prospective studies measuring NP in people with stable coronary
      disease who were followed-up for all cause mortality, coronary or cardiovascular
      events. DATA EXTRACTION: Two independent reviewers categorised studies according
      to the American Heart Association phase of study, and extracted data according to
      the study reporting guidelines from the American Heart Association and REMARK.
      RESULTS: Systematic review of 19 studies found 17 which were phase 2, reporting
      an association between NP and events, two phase 3 studies, statistically
      examining the incremental prognostic value of NP, but no studies assessing
      whether NP predicted risk sufficiently to change management (phase 4), improve
      clinical outcomes (phase 5) or cost effectiveness (phase 6). No study referred to
      a statistical analytic protocol. Meta-analysis of 14 studies, reporting 18,841
      patients and 1655 outcome events, found an RR for events of 3.28 (95% CI 2.45 to
      4.38) comparing top versus bottom third of NP. This effect was 26% lower among
      the five studies which adjusted for a priori confounders (age, sex, renal
      function and left ventricular function) and 38% lower when adjusting for
      publication bias (Egger's p=0.001). CONCLUSION: The unbiased strength of
      association of NP with prognosis in stable coronary disease is unclear, and there
      is a lack of reports of clinically useful measures of prediction and
      discrimination or studies relating NP levels to clinical decision making. The
      available literature is confined to early phases and is of limited clinical
      usefulness.

PMID- 22388699
TI  - Computational identification of microRNAs and their targets in cassava (Manihot
      esculenta Crantz.).
AB  - MicroRNAs (miRNAs) are a newly discovered class of noncoding endogenous small
      RNAs involved in plant growth and development as well as response to
      environmental stresses. miRNAs have been extensively studied in various plant
      species, however, only few information are available in cassava, which serves as
      one of the staple food crops, a biofuel crop, animal feed and industrial raw
      materials. In this study, the 169 potential cassava miRNAs belonging to 34 miRNA
      families were identified by computational approach. Interestingly, mes-miR319b
      was represented as the first putative mirtron demonstrated in cassava. A total of
      15 miRNA clusters involving 7 miRNA families, and 12 pairs of sense and antisense
      strand cassava miRNAs belonging to six different miRNA families were discovered.
      Prediction of potential miRNA target genes revealed their functions involved in
      various important plant biological processes. The cis-regulatory elements
      relevant to drought stress and plant hormone response were identified in the
      promoter regions of those miRNA genes. The results provided a foundation for
      further investigation of the functional role of known transcription factors in
      the regulation of cassava miRNAs. The better understandings of the complexity of
      miRNA-mediated genes network in cassava would unravel cassava complex biology in
      storage root development and in coping with environmental stresses, thus
      providing more insights for future exploitation in cassava improvement.

PMID- 22388700
TI  - Coexistence of antiferromagnetic and ferromagnetic orders at remanent state in
      epitaxial multiferroic Bi2FeCrO6 nanostructures.
AB  - We report the local electronic and magnetic properties of Bi(2)FeCrO(6)
      nanostructures by element-specific polarized x-ray techniques. Sizable magnetic
      ordering in the remanent state is observed at room temperature for both Fe and Cr
      ions. The Bi(2)FeCrO(6) system offers an example of d(5)-d(3) magnetic
      superexchange interaction with a magnetic order for both Fe and Cr, which are
      both formally in the  + 3 valence state. The results suggest a coexistence of
      antiferromagnetic and ferromagnetic superexchange interaction between Fe and Cr
      spins in the nanostructures at the remanent state and at room temperature.

PMID- 22388701
TI  - QCT and QM calculations of the Cl(2P) + NH3 reaction: influence of the reactant
      well on the dynamics.
AB  - A detailed dynamics study, using both quasi-classical trajectory (QCT) and
      reduced-dimensional quantum mechanical (QM) calculations, was carried out to
      understand the reactivity and mechanism of the Cl((2)P) + NH(3)-> HCl + NH(2) gas
      phase reaction, which evolves through deep wells in the entry and exit channels.
      The calculations were performed on an analytical potential energy surface
      recently developed by our group, PES-2010 [M. Monge-Palacios, C. Rangel, J. C.
      Corchado and J. Espinosa-Garcia, Int. J. Quantum. Chem., 2011], together with a
      simplified model surface, mod-PES, in which the reactant well is removed to
      analyze its influence. The main finding was that the QCT and QM methods show a
      change of the reaction probability with collision energy, suggesting a change of
      the atomic-level mechanism of reaction with energy. This change disappeared when
      the mod-PES was used, showing that the behaviour at low energies is a direct
      consequence of the existence of the reactant well. Analysis of the trajectories
      showed that different mechanisms operate depending on the collision energy. Thus,
      while at high energies (E(coll) > 5 kcal mol(-1)) practically all trajectories
      are direct, at low energies (E(coll) < 3 kcal mol(-1)) the trajectories are
      indirect, i.e., with the mediation of a trapping complex in the entry and/or the
      exit wells. The reactant complex allows repeated encounters between the
      reactants, increasing the reaction probability at low energies. The differential
      cross section results reinforce this change of mechanism, showing also the
      influence of the reactant well on this reaction. Thus, the PES-2010 surface
      yields a forward-backward symmetry in the scattering, while when the reactant
      well is removed with the mod-PES the shape is more isotropic.

PMID- 22388703
TI  - Perioperative temperature management in day-case surgical patients.

PMID- 22388702
TI  - Datex-Ohmeda NeuroMuscular Transmission electromyography module artefacts in
      clinical practice:  case report and retrospective chart review.

PMID- 22388705
TI  - Preparation of the Drager Fabius CE and Drager Zeus anaesthetic machines for
      patients susceptible to malignant hyperthermia.
AB  - CONTEXT: Malignant hyperthermia may follow exposure to trace quantities of
      inhalational anaesthetics. In susceptible patients, the complete avoidance of
      these triggers is advised when possible; however, failing this, it is essential
      to washout or purge the anaesthesia machine of residual inhalational
      anaesthetics. OBJECTIVE: This study examined the washout profile of sevoflurane
      from the Drager Fabius CE and the Drager Zeus machines. DESIGN: The washout
      profile of sevoflurane was measured from the Fabius CE and Zeus anaesthesia
      machines following a standard period of exposure. The disposable tubing, CO2
      absorber and other components of each machine were then replaced to examine their
      impact on the retention of sevoflurane. The effect of autoclaving the ventilator
      diaphragm and non-disposable ventilator tube or substituting for a new diaphragm
      and ventilation tube were examined in later parts of this study. SETTING:
      University teaching hospital. MAIN OUTCOME MEASURE: Time taken to reach 5 parts
      per million of sevoflurane when machines underwent standard washout with fresh
      gas flush. RESULTS: The concentration of sevoflurane reached 5 parts per million
      in the Fabius CE machines after an mean (SD) of 140 min (46) at a fresh gas flow
      (FGF) of 10 l min(-1). The time taken for sevoflurane to reach 5 parts per
      million was significantly reduced when the ventilator diaphragm and non
      disposable tube were replaced with either new or autoclaved components [14 or 22
      min, respectively (P = 0.017, P = 0.031)]. The concentration of sevoflurane
      reached 5 parts per million in the Zeus machines after an mean (SD) of 85 min (6)
      at a fresh gas flow of 10 l min(-1). When the fresh gas flow was increased to 18
      l min(-1) (the maximum allowable), the time to reach 5 parts per million was
      reduced to 16 min. CONCLUSION: When preparing the Fabius CE for the malignant
      hyperthermia susceptible patient, remove the vaporiser, replace the disposable
      tubing, the reservoir bag and the CO2 absorber. Replace the ventilator diaphragm
      and non-disposable ventilator tube with new or autoclaved components and flush
      the machine at 10 l min(-1) for at least 36 min. When preparing the Zeus, remove
      the vaporiser, replace the disposable tubing, the reservoir bag and CO2 absorber
      and flush at a fresh gas flow of 10 l min(-1) for at least 90 min. In both the
      Fabius and Zeus, continue at a fresh gas flow of 10 l min(-1) for the duration of
      the operation.

PMID- 22388706
TI  - The 90% effective dose of a sufentanil bolus for the management of painful
      positioning in intubated patients in the ICU.
AB  - CONTEXT: Pain and discomfort arising from the routine care of intubated patients
      in the ICU is managed by continuous infusion of narcotic and sedative drugs.
      There is benefit in keeping infusion rates low because lightening sedation
      improves clinical outcome, but this risks breakthrough pain. Management of this
      discomfort by bolus administration could permit lower background infusion rates,
      but the lowest effective bolus dose of sufentanil to achieve this is unknown.
      OBJECTIVE: The aim of this study was to determine the effective analgesic dose in
      90% of intubated patients (ED90) in the ICU given bolus sufentanil. Pain was
      assessed using a Behavioural Pain Scale (BPS) requiring a score of 3-4 during
      moving to the lateral decubitus position. DESIGN: Prospective, dose response
      study. SETTING: A 16-bed multidisciplinary ICU in a French university hospital.
      Study period was from January to June 2010. PATIENTS: Intubated and ventilated
      patients were eligible for the study once they had reached a BPS of 3 or 4 and
      Ramsay score of 3-5 within 48 h of admission to the ICU. INTERVENTION: The
      analgesic efficacy of a sufentanil bolus was measured during successive lateral
      decubitus positioning over a 72-h study period, using the BPS scale. The dose was
      increased with each subsequent turn to lateral decubitus until a BPS score of 3-4
      was obtained (dose escalation, starting at zero). MAIN OUTCOME MEASURES: BPS,
      Ramsay score, heart rate and mean arterial pressure were collected before and
      during each procedure. RESULTS: A total of 25 patients were enrolled over 6
      months. The ED90 bolus for sufentanil was 0.15 MUg kg, but 40% of the patients
      subsequently demonstrated increased BPS with this dose. CONCLUSION: The effective
      dose in 90% was 0.15 MUg kg during the first 5 days of sedation. There were no
      adverse effects. A pre-emptive sufentanil bolus can be used to treat anticipated
      pain in the ICU. Regular and frequent assessments of acute pain and sedation are
      essential for adjusting the dose, on a case-by-case basis. This strategy may help
      clinicians to keep background infusions of sedatives and narcotics as low as
      possible and may improve clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01356732.

PMID- 22388707
TI  - Limitation of elbow flexion in a patient with congenital radioulnar synostosis.

PMID- 22388708
TI  - A modification of the Souquet advancement flap in fingertip reconstruction.
AB  - The Hueston local transposition flap and Souquet advancement flap are two
      commonly employed options in fingertip reconstruction after amputation. Both are
      rectangular flaps rotated so that the free edge advances to cover the defect in
      the fingertip. They differ in that the Hueston flap does not include the
      neurovascular bundle in the free edge, while the Souquet flap does include the
      bundle. In consequence, the Hueston advances further but is half insensate, while
      the Souquet advances far less but is sensate. We describe a modification of the
      Souquet flap that retains the advantages of both flaps while avoiding the
      drawbacks.

PMID- 22388709
TI  - A spatio-temporal absorbing state model for disease and syndromic surveillance.
AB  - Reliable surveillance models are an important tool in public health because they
      aid in mitigating disease outbreaks, identify where and when disease outbreaks
      occur, and predict future occurrences. Although many statistical models have been
      devised for surveillance purposes, none are able to simultaneously achieve the
      important practical goals of good sensitivity and specificity, proper use of
      covariate information, inclusion of spatio-temporal dynamics, and transparent
      support to decision-makers. In an effort to achieve these goals, this paper
      proposes a spatio-temporal conditional autoregressive hidden Markov model with an
      absorbing state. The model performs well in both a large simulation study and in
      an application to influenza/pneumonia fatality data.

PMID- 22388710
TI  - Corticosteroid plus pentoxifylline is not better than corticosteroid alone for
      improving survival in severe alcoholic hepatitis (COPE trial).
AB  - BACKGROUND: Corticosteroids and pentoxifylline reduce short-term mortality in
      severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both
      drugs may lead to better survival, but has not yet been studied. AIM: To compare
      the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids
      alone in improving survival of SAH patients. METHODS: Of the 111 patients
      screened, 70 patients with SAH (Maddrey discriminant function (MDF) >= 32) were
      enrolled. Patients with active infection, bleeding, renal failure, or
      pancreatitis were excluded. Treatment was given for four weeks to group A (n =
      36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n
      = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are
      expressed as median (range) or percentage. RESULTS: Baseline characteristics of
      the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6
      140.2)). Four-week and six-month survival in groups A and B were not
      significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six
      month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients
      in group A and 64.7% in group B had a Lille score <0.45 (p = 0.473). Six-month
      survival was significantly higher for patients with a Lille Score <0.45 than for
      those with a Lille score >=0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs.
      0%, p = 0.0304). Biological improvement at 28 days was significant for both
      groups; however, the difference between the groups was not significant.
      CONCLUSIONS: For patients with severe alcoholic hepatitis, a combination of
      corticosteroids and pentoxifylline has no additional survival advantage compared
      with corticosteroids alone.

PMID- 22388711
TI  - Brucellosis due to Brucella suis in a swine herd associated with a human clinical
      case in the State of Sao Paulo, Brazil.
AB  - Brucella suis has been recognized as the major etiological agent of human
      brucellosis in areas free from Brucella melitensis infection. However, with
      changes in swine management, the occurrence of swine brucellosis has decreased as
      has the human incidence of B. suis infection. A swine brucellosis outbreak within
      a herd from Jaboticabal (Sao Paulo, Brazil) was detected in July 2006. The herd
      comprised approximately 300 sows and 1,500 finishing animals. Many sows within
      this herd experienced abortions, while others exhibited vaginal discharge; three
      sows suffered posterior paralysis. Among 271 sows, 254 (93.7%) tested positive
      for brucellosis by complement fixation, and among 62 randomly bled finishing
      animals, 17 (27.4%) also tested positive. The B. suis biovar 1 was cultured from
      14 aborted fetuses and six sows. Brucella was identified using routine methods.
      Fourteen farm workers were tested using agglutination tests, with three workers
      showing evidence of Brucella antibody titers. A 39-year-old woman, who worked
      with maternal pigs and had direct contact with aborted fetuses, presented an
      agglutinating titer of 480 IU/mL and displayed clinical signs of infection. Our
      findings suggest that despite a reduction of swine brucellosis throughout Brazil,
      B. suis infection still occurs, thereby posing a zoonotic risk.

PMID- 22388714
TI  - 14 principles of ethical conduct in practice.

PMID- 22388712
TI  - The specific targeting of immune regulation: T-cell responses against Indoleamine
      2,3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is
      implicated in suppressing T-cell immunity in many settings including cancer. In
      recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell
      reactivity against IDO in the tumor microenvironment of different cancer patients
      as well as in the peripheral blood of both cancer patients and to a lesser extent
      in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were
      peptide-specific, cytotoxic effector cells, which are able to recognize and kill
      IDO-expressing cells including tumor cells as well as dendritic cells.
      Consequently, IDO may serve as a widely applicable target for immunotherapeutic
      strategies with a completely different function as well as expression pattern
      compared to previously described antigens. IDO constitutes a significant counter
      regulatory mechanism induced by pro-inflammatory signals, and IDO-based
      immunotherapy may consequently be synergistic with additional immunotherapy. In
      this regard, we have shown that the presence of IDO-specific T cells boosted
      immunity against CMV and tumor antigens by eliminating IDO(+) suppressive cells
      and changing the regulatory microenvironment. The current review summarizes
      current knowledge of IDO as a T-cell antigen, reports the initial results that
      are suggesting a general function of IDO-specific T cells in immunoregulation,
      and discusses future opportunities.

PMID- 22388715
TI  - Legal fundamentals of contracting for healthcare.

PMID- 22388713
TI  - Head orthesis therapy in infants with unilateral positional plagiocephaly: an
      interdisciplinary approach to broadening the range of orthodontic treatment.
AB  - OBJECTIVE: Unilateral positional plagiocephaly is the most common deformity of
      the head in infants. As part of a prospective controlled clinical study, the
      pathomorphology of the positional plagiocephaly in early infancy was examined.
      The goal was to use noninvasive three-dimensional (3D) imaging to generate, for
      the first time ever, a standard database of infants without head deformities, to
      quantify the asymmetry of the positional plagiocephaly, and to evaluate the
      effectiveness of functional growth control using head orthesis. PATIENTS AND
      METHODS: In the present study, 3D soft-tissue data of the entire head were
      collected from a total of 40 infants: 20 with positional plagiocephaly (6.0 +/-
      0.97 months) and 20 infants without a head deformity (6.4 +/- 0.3 months).
      Functional growth was controlled using a custom-made head orthesis. To evaluate
      the therapy, pre- and posttherapeutic scans were evaluated in three dimensions.
      RESULTS: Compared with the control group, infants with positional plagiocephaly
      demonstrated a reduced maximum length of the head, an increased head height, a
      shift in the ear axis as well as asymmetric anterior and posterior volumes of the
      neurocranium in lateral comparisons. Therapy using head orthesis led to a
      significant improvement of the asymmetry, with a reduction of the diagonal
      difference and an adjustment of the posterior volumes. CONCLUSION: Conservative
      growth control of extrinsically deformed infant skulls represents an
      interdisciplinary medical expansion of the orthodontic therapeutic spectrum. To
      prevent potential effects of positional plagiocephaly on the viscerocranium, head
      orthesis therapy is advisable in infancy.

PMID- 22388716
TI  - Roadmap for dealing with contractor employees.

PMID- 22388717
TI  - Have you made an unauthorized commitment lately?

PMID- 22388718
TI  - Fiscal law overview.

PMID- 22388719
TI  - Transitioning third party collections from third world processes.

PMID- 22388720
TI  - Expanding use of technology transfer mechanisms within the Army's medical
      treatment facilities.

PMID- 22388721
TI  - Social media: some things to consider before creating an online presence.

PMID- 22388722
TI  - Army medical training agreements.

PMID- 22388723
TI  - Affiliation agreements.

PMID- 22388724
TI  - Public health emergency law: a primer for leaders and managers in the military.

PMID- 22388725
TI  - Army paralegals and paralegal specialists.

PMID- 22388726
TI  - CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid
      childhood acute lymphoblastic leukemia.
AB  - Despite their apparently good prognosis ~15% of high hyperdiploid (HD) childhood
      acute lymphoblastic leukemia (ALL) cases relapse. To search for responsible risk
      factors we determined copy number aberrations as well as copy neutral loss of
      heterozygosity (LOH) in 13 matched diagnosis and relapse samples and added the
      data of the only three available cases from the literature. Deletions and copy
      neutral LOH in 3 and 2 of the 16 cases directed us to the histone-modifying CREB
      binding protein (CREBBP) gene, whose functional impairment is implicated in drug
      resistance. We therefore screened all samples for mutations in this gene and
      discovered 9 acquired sequence mutations in 7/16 cases, leading to an overall
      frequency of somatic CREBBP aberrations in HD ALL relapse cases of 63% that is
      considerably higher than that of the reported, mainly non-HD ALL (18.3%).
      Moreover, mutations in HD cases occur almost exclusively in the HAT domain (8/9;
      89%). Hot spot mutations are present at diagnosis in 18.8% of relapsing HD ALL
      cases but in none of 40 respective cases remaining in long-term remission. Thus,
      the particular high incidence of CREBBP mutations in relapse-prone HD ALL cases
      could eventually be exploited for refined risk stratification and customized
      treatment in this genetic subgroup.

PMID- 22388727
TI  - Frequent loss of RAF kinase inhibitor protein expression in acute myeloid
      leukemia.
AB  - RAF kinase inhibitor protein (RKIP) is a negative regulator of the RAS-mitogen
      activated protein kinase/extracellular signal-regulated kinase signaling cascade.
      We investigated its role in acute myeloid leukemia (AML), an aggressive
      malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Western
      blot analysis revealed loss of RKIP expression in 19/103 (18%) primary AML
      samples and 4/17 (24%) AML cell lines but not in 10 CD34+ HSPC specimens. In in
      vitro experiments with myeloid cell lines, RKIP overexpression inhibited cellular
      proliferation and colony formation in soft agar. Analysis of two cohorts with 103
      and 285 AML patients, respectively, established a correlation of decreased RKIP
      expression with monocytic phenotypes. RKIP loss was associated with RAS mutations
      and in transformation assays, RKIP decreased the oncogenic potential of mutant
      RAS. Loss of RKIP further related to a significantly longer relapse-free survival
      and overall survival in uni- and multivariate analyses. Our data show that RKIP
      is frequently lost in AML and correlates with monocytic phenotypes and mutations
      in RAS. RKIP inhibits proliferation and transformation of myeloid cells and
      decreases transformation induced by mutant RAS. Finally, loss of RKIP seems to be
      a favorable prognostic parameter in patients with AML.

PMID- 22388729
TI  - The role of hearing preservation on electrical thresholds and speech performances
      in cochlear implantation.
AB  - OBJECTIVE: The purpose of this study was to verify if the preservation of
      residual hearing after cochlear implantation in classic adult cochlear implant
      candidates implanted with a perimodiolar electrode correlates with the electric
      thresholds and with speech perception measures. STUDY DESIGN: Retrospective
      study. SETTING: Cochlear Implant Center at a tertiary referral University
      Hospital. PATIENTS: Forty-one patients with cochlear implant were involved in our
      study. They were subdivided into 2 groups according to the average preoperative
      hearing loss at the frequencies of 125 and 250 Hz (low-frequency pure tone
      average [LFPTA]). Group A included 21 patients with a mean LFPTA of 90 dB HL or
      lower; group B included 20 patients with a mean LFPTA of greater than 90 dB HL.
      They underwent 12 months' follow-up after cochlear implantation, including
      standard audiologic investigation, speech discrimination tests, and electrical
      measurements. RESULTS: No significant differences were found in speech perception
      tests among groups. In group A, hearing was preserved in 8 (group A1) and was
      lost in 13 patients (group A2); the postoperative LFPTA was significantly better
      (p < 0.0001) in A1. Group A1 patients present significantly higher C values (p <
      0.0001) than the other 2 groups, and the dynamic range was therefore
      significantly wider (p < 0.001). CONCLUSION: Preservation of residual hearing
      should be attempted in all cases. In fact, although effects on the speech
      perception are not evident with the standard evaluation, larger electrical
      dynamic range can be achieved and may represent a sign of cochlear "well-being,"
      potentially allowing a more complex electric stimulation of the nerve.

PMID- 22388730
TI  - Recurrence of benign paroxysmal positional vertigo.
AB  - OBJECTIVE: To determine the recurrence rate of benign positional paroxysmal
      vertigo (BPPV) and the factors associated to such recurrences. STUDY DESIGN:
      Prospective study. METHOD: Sixty-nine consecutive patients treated for first
      episode of BPPV. STUDY PERIOD: 63 months. Mean follow-up: 47 months. RESULTS: The
      recurrence rate was 27%. Fifty percent of recurrences occurred in the first 6
      months. Nineteen patients had 1 or more recurrence of BPPV; 10 had 1 recurrence,
      7 patients had 2, and 2 patients had 3 recurrences. There was no significant
      difference in the recurrence rate according to sex, age, side, cause of BPPV, or
      instability after successful treatment. Multi-canal BPPV (log-rank, p = 0.024)
      and anterior canal BPPV (log-rank, p = 0.029) showed a significantly greater
      tendency to recur and to do so earlier. There was a significant difference in
      time to recurrence related to the number of maneuvers used to resolve the initial
      BPPV episode (log-rank, p = 0.023). Except for cases of BPPV secondary to
      labyrinthitis or neurolabyrinthitis, at least 70% of the recurrences affected a
      different side and/or different canal than the primary BPPV. CONCLUSION: The
      recurrence rate of BPPV is 27%, and relapse largely occurs in the first 6 months.
      When BPPV recurrence is suspected, every canal on both sides must be investigated
      because it is the BPPV syndrome that recurs, rather than BPPV affecting a
      particular side or canal. Complex cases of BPPV have a greater risk of
      recurrence.

PMID- 22388731
TI  - Prevalence and hospital resource utilization in tympanoplasty and revision
      tympanoplasty:  a population-based comparative study.
AB  - OBJECTIVE: To compare trends, risk factors, prevalence rates, and hospital
      resource utilization between tympanoplasty and revision tympanoplasty. STUDY
      DESIGN: Retrospective review. SETTING: All hospitals. PATIENTS: This study
      analyzed 58,038 tympanoplasty procedures and 953 revision tympanoplasty
      procedures performed in Taiwan from 1996 to 2007. MAIN OUTCOME MEASURES:
      Administrative claims data from the Bureau of National Health Insurance of
      Taiwan. Odds ratio and 95% confidence intervals were calculated to assess the
      relative change rate. Regression models were used to predict length of stay (LOS)
      and hospital treatment costs. RESULTS: The number of tympanoplasties performed
      per 100,000 patients was 22.97 in 1996. It gradually increased to 26.7 in 2001
      and then gradually decreased to 16.61 in 2007. The number of revision
      tympanoplasties per 100,000 patients during the same period, however, was 0.29 to
      0.48. During the study period, the LOS associated with both tympanoplasty and
      revision tympanoplasty decreased, whereas hospital treatment costs associated
      with the 2 procedures increased. Considerably decreased LOS and increased
      hospital treatment costs were associated with age, sex, number of comorbidities,
      hospital level, hospital volume, surgeon volume, and LOS. CONCLUSION: High-volume
      hospitals and surgeons obtained the largest improvements in tympanoplasty
      outcomes, particularly in LOS and hospital treatment costs. Health care providers
      and patients should recognize that hospital resource utilization may depend on
      hospital attributes as well as patient attributes.

PMID- 22388732
TI  - Gene therapy for cisplatin-induced ototoxicity: a systematic review of in vitro
      and experimental animal studies.
AB  - OBJECTIVE: Ototoxicity is a frequent adverse event of cisplatin treatment. No
      therapy is currently available for cisplatin-induced ototoxicity. A systematic
      review of experimental animal studies and in vitro experiments was conducted to
      evaluate gene therapy as a potential future therapeutic option. DATA SOURCES:
      Eligible studies were identified through searches of electronic databases Ovid
      MEDLINE, Ovid MEDLINE In-Process, Embase, PubMed, Biosis Previews, Scopus, ISI
      Web of Science, and The Cochrane Library. STUDY SELECTION: Articles obtained from
      the search were independently reviewed by 2 authors using specific criteria to
      identify experimental animal studies and in vitro experiments conducted to
      evaluate gene therapy for cisplatin-induced ototoxicity. No restriction was
      applied to publication dates or languages. DATA EXTRACTION: Data extracted
      included experiment type, cell type, species, targeted gene, gene expression,
      method, administration, inner ear site evaluated, outcome measures for
      cytotoxicity, and significant results. RESULTS: Fourteen articles were included
      in this review. In vitro and in vivo experiments have been performed to evaluate
      the potential of gene expression manipulation for cisplatin-induced ototoxicity.
      Twelve different genes were targeted including NTF3, GDNF, HO-1, XIAP, Trpv1,
      BCL2, Otos, Nfe2l2, Nox1, Nox3, Nox4, and Ctr1. All of the included articles
      demonstrated a benefit of gene therapy on cytotoxicity caused by cisplatin.
      CONCLUSION: Experimental animal studies and in vitro experiments have
      demonstrated the efficacy of gene therapy for cisplatin-induced ototoxicity.
      However, further investigation regarding safety, immunogenicity, and consequences
      of genetic manipulation in the inner ear tissues must be completed to develop
      future therapeutic options.

PMID- 22388733
TI  - Expression of the aryl hydrocarbon receptor is not required for the
      proliferation, migration, invasion, or estrogen-dependent tumorigenesis of MCF-7
      breast cancer cells.
AB  - The AhR was initially identified as a ligand-activated transcription factor
      mediating effects of chlorinated dioxins and polycyclic aromatic hydrocarbons on
      cytochrome P450 1 (CYP1) expression. Recently, evidence supporting involvement of
      the AhR in cell-cycle regulation and tumorigenesis has been presented. To further
      define the roles of the AhR in cancer, we investigated the effects of AhR
      expression on cell proliferation, migration, invasion, and tumorigenesis of MCF-7
      human breast cancer cells. In these studies, the properties of MCF-7 cells were
      compared with those of two MCF-7-derived sublines: AH(R100) , which express
      minimal AhR, and AhR(exp) , which overexpress AhR. Quantitative PCR, Western
      immunoblots, 17beta-estradiol (E2 ) metabolism assays, and ethoxyresorufin O
      deethylase assays showed the lack of AhR expression and AhR-regulated CYP1
      expression in AH(R100) cells, and enhanced AhR and CYP1 expression in AhR(exp)
      cells. In the presence of 1 nM E2 , rates of cell proliferation of the three cell
      lines showed an inverse correlation with the levels of AhR mRNA. In comparison
      with MCF-7 and AhR(exp) cells, AH(R100) cells produced more colonies in soft agar
      and showed enhanced migration and invasion in chamber assays with E2 as the
      chemoattractant. Despite the lack of significant AhR expression, AH(R100) cells
      retained the ability to form tumors in severe combined immunodeficient mice when
      supplemented with E2 , producing mean tumor volumes comparable to those observed
      with MCF-7 cells. These studies indicate that, while CYP1 expression and
      inducibility are highly dependent on AhR expression, the proliferation, invasion,
      migration, anchorage-independent growth, and estrogen-stimulated tumor formation
      of MCF-7 cells do not require the AhR.

PMID- 22388734
TI  - The SUMO protease SENP7 is a critical component to ensure HP1 enrichment at
      pericentric heterochromatin.
AB  - SUMOylation promotes targeting of HP1alpha to pericentric heterochromatin. Here
      we identify the SUMO-specific protease SENP7 in mouse as a maintenance factor for
      HP1alpha accumulation at this location. SENP7 interacts directly with HP1alpha,
      localizes at HP1-enriched pericentric domains and can deconjugate SUMOylated
      HP1alpha in vivo. Depletion of SENP7 delocalizes HP1alpha from pericentric
      heterochromatin without affecting H3K9me3 levels. We propose that following
      targeting of HP1alpha, a subsequent deSUMOylation event enables HP1alpha
      retention at these domains.

PMID- 22388735
TI  - Structure of the human metapneumovirus fusion protein with neutralizing antibody
      identifies a pneumovirus antigenic site.
AB  - Human metapneumovirus and respiratory syncytial virus cause lower respiratory
      tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by
      refolding from a metastable pre-fusion to a stable post-fusion conformation. F is
      also a major target of the neutralizing antibody response. Here we show that a
      potently neutralizing anti-human metapneumovirus antibody (DS7) binds a
      structurally invariant domain of F, revealing a new epitope that could be
      targeted in vaccine development.

PMID- 22388736
TI  - The structure of the ASAP core complex reveals the existence of a Pinin
      containing PSAP complex.
AB  - The ASAP complex interacts with the exon-junction complex (EJC), a messenger
      ribonucleoprotein complex involved in post-transcriptional regulation. The three
      ASAP subunits (Acinus, RNPS1 and SAP18) have been individually implicated in
      transcriptional regulation, pre-mRNA splicing and mRNA quality control. To shed
      light on the basis for and consequences of ASAP's interaction with the EJC, we
      have determined the 1.9-A resolution structure of a eukaryotic ASAP core complex.
      The RNA-recognition motif of RNPS1 binds to a conserved motif of Acinus with a
      recognition mode similar to that observed in splicing U2AF proteins. The Acinus
      RNPS1 platform recruits the ubiquitin-like domain of SAP18, forming a ternary
      complex that has both RNA- and protein-binding properties. Unexpectedly, our
      structural analysis identified an Acinus-like motif in Pinin, another EJC
      associated splicing factor. We show that Pinin physically interacts with RNPS1
      and SAP18, forming an alternative ternary complex, PSAP.

PMID- 22388737
TI  - Topoisomerase I poisoning results in PARP-mediated replication fork reversal.
AB  - Topoisomerase I (Top1) releases torsional stress during DNA replication and
      transcription and is inhibited by camptothecin and camptothecin-derived cancer
      chemotherapeutics. Top1 inhibitor cytotoxicity is frequently linked to double
      strand break (DSB) formation as a result of Top1 being trapped on a nicked DNA
      intermediate in replicating cells. Here we use yeast, mammalian cell lines and
      Xenopus laevis egg extracts to show that Top1 poisons rapidly induce replication
      fork slowing and reversal, which can be uncoupled from DSB formation at sublethal
      inhibitor doses. Poly(ADP-ribose) polymerase activity, but not single-stranded
      break repair in general, is required for effective fork reversal and limits DSB
      formation. These data identify fork reversal as a means to prevent chromosome
      breakage upon exogenous replication stress and implicate proteins involved in
      fork reversal or restart as factors modulating the cytotoxicity of replication
      stress-inducing chemotherapeutics.

PMID- 22388739
TI  - Bioelectricity production using a new electrode in a microbial fuel cell.
AB  - Electrode materials play a key role in enhancing the electricity generation in
      the microbial fuel cell (MFC). In this study, a new material (Ti-TiO(2)) was used
      as an anode electrode and compared with a graphite electrode for electricity
      generation. Current densities were 476.6 and 31 mA/m(2) for Ti-TiO(2) and
      graphite electrodes, respectively. The PCR-DGGE analysis of enriched microbial
      communities from estuary revealed that MFC reactors were dominated by Shewanella
      haliotis, Enterococcus sp., and Enterobacter sp. Bioelectrochemical kinetic works
      in the MFC with Ti-TiO(2) electrode revealed that the parameters by non-linear
      curve fitting with the confidence bounds of 95% gave good fit with the kinetic
      constants of eta (difference between the anode potential and anode potential
      giving one-half of the maximum current density) = 0.35 V, K (s) (Half-saturation
      constant) = 2.93 mM and J (max) = 0.39 A/m(2) for T = 298 K and F = 96.485 C/mol
      e(-). From the results observed, it is clear that Ti-TiO(2) electrode is a
      promising candidate for electricity generation in MFC.

PMID- 22388738
TI  - A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71.
AB  - Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in
      children that can cause severe central nervous system disease and death. No
      vaccine or antiviral therapy is available. High-resolution structural analysis of
      the mature virus and natural empty particles shows that the mature virus is
      structurally similar to other enteroviruses. In contrast, the empty particles are
      markedly expanded and resemble elusive enterovirus-uncoating intermediates not
      previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid
      are collapsed in this expanded particle, providing a detailed explanation of the
      mechanism for receptor-binding triggered virus uncoating. These structures
      provide a model for enterovirus uncoating in which the VP1 GH loop acts as an
      adaptor-sensor for cellular receptor attachment, converting heterologous inputs
      to a generic uncoating mechanism, highlighting new opportunities for therapeutic
      intervention.

PMID- 22388740
TI  - Characterization of a commercial cellulase for hydrolysis of agroindustrial
      substrates.
AB  - This work is focused on the characterization of a commercial cellulase in terms
      of optimum pH and temperature, stability to pH and temperature and affinity of
      this enzyme to several substrates, determining the Michaelis-Menten parameters.
      Maximum activity of cellulase was obtained for the temperature range from 40 to
      50  degrees C and pH from 5.2 to 5.5. Enzyme activity decreased only 15% after
      150 h of reaction at temperatures between 30 and 50  degrees C. No loss of
      activity was observed at pH 5.0 and 5.5. The cellulase showed satisfactory
      results in the hydrolysis of agroindustrial substrates, since similar activity
      was verified on filter paper and other agroindustrial substrates.

PMID- 22388742
TI  - Physical activity promotion in schools: which strategies do schools (not)
      implement and which socioecological factors are associated with implementation?
AB  - We studied the implementation and associated factors of strategies (e.g. sports
      after school and during lunch break, active schoolyards, active school commuting)
      and organizational principles (e.g. safe bike racks, pupil involvement) that
      facilitate the physical activity (PA)-promoting role of schools. Key
      representatives of 111 elementary and 125 secondary schools filled out an online
      survey. Less than half of the elementary schools organized sports during lunch
      break or after school. In secondary schools the least implemented strategies were
      the promotion of active school commuting and after-school sports. In general
      pupil, parental and community involvement scored low. Better knowledge of
      community schools and having attended in-service training were associated with
      higher implementation scores in elementary and secondary schools. Better
      implementation of the strategies was found in larger schools. Participation in
      activities from the School Sports Association and more perceived interest from
      parents and the school board were also associated with higher implementation
      scores. In conclusion, knowledge of community schools and in-service training
      next to sufficient human resources are potential key factors to promote PA.
      Efforts are needed to convince and help schools to increase parental and pupil
      involvement and to build a policy on school-community partnerships.

PMID- 22388741
TI  - Intensification of high cell-density cultivations of rE. coli for production of
      S. pneumoniae antigenic surface protein, PspA3, using model-based adaptive
      control.
AB  - This work proposes an innovative methodology to control high density fed-batch
      cultures of E. coli, based on measurements of the concentration of dissolved
      oxygen and on estimations of the cellular specific growth rate (u), of the yield
      of biomass/limiting substrate (Y (xs)) and of the maintenance coefficient (m).
      The underlying idea is to allow cells to grow according to their metabolic
      capacity, without the constraints inherent to pre-set growth rates. Cellular
      concentration was assessed on-line through a capacitance probe. Three
      configurations of the control system were compared: (1) pre-set value for the
      three control parameters; (2) continuously updating u; (3) updating u, Y (xs) and
      m. Implementation of an efficient noise filter for the signal of the capacitance
      probe was essential for a good performance of the control system. The third
      control strategy, within the framework of an adaptive model-based control, led to
      the best results, with biomass productivity reaching 9.2 g(DCW)/L/h.

PMID- 22388743
TI  - Electronic excitation spectra of the [Ir(ppy)2(bpy)]+ photosensitizer bound to
      small silver clusters Ag(n) (n = 1-6).
AB  - The changes in nature and order of the excited electronic states of the
      photosensitizer [Ir(ppy)(2)(bpy)](+) upon binding to small silver clusters, Ag(n)
      (n = 1-6), were studied theoretically using the linear response TDDFT method with
      the range-separated LC-BLYP functional. Binding energies and localization of HOMO
      and LUMO orbitals are found to oscillate with the number of silver atoms. Special
      emphasis is put on the discussion of long-range charge transfer transitions
      between the photosensitizer and the silver cluster. The energies of these
      transitions were found to be only slightly dependent on the relative orientations
      of both fragments, but strongly dependent on the intermolecular distance. The
      absorption spectrum of the combined system does not show a systematic trend with
      respect to cluster size, but it is strongly modified by the charge transfer
      transitions. Possible photophysical processes of the systems containing larger
      clusters are discussed.

PMID- 22388744
TI  - Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation.
AB  - Large bone defects naturally regenerate via a highly vascularized tissue which
      progressively remodels into cartilage and bone. Current approaches in bone tissue
      engineering are restricted by delayed vascularization and fail to recapitulate
      this stepwise differentiation toward bone tissue. Here, we use the morphogen
      Sonic Hedgehog (Shh) to induce the in vitro organization of an endothelial
      capillary network in an artificial tissue. We show that endogenous Hedgehog
      activity regulates angiogenic genes and the formation of vascular lumens.
      Exogenous Shh further induces the in vitro development of the vasculature
      (vascular lumen formation, size, distribution). Upon implantation, the in vitro
      development of the vasculature improves the in vivo perfusion of the artificial
      tissue and is necessary to contribute to, and enhance, the formation of de novo
      mature bone tissue. Similar to the regenerating callus, the artificial tissue
      undergoes intramembranous and endochondral ossification and forms a trabecular
      like bone organ including bone-marrow-like cavities. These findings open the door
      for new strategies to treat large bone defects by closely mimicking natural
      endochondral bone repair.

PMID- 22388745
TI  - Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain
      inhibitor that also augments ionizing radiation.
AB  - Protein-protein interactions mediated by ubiquitin-like (Ubl) modifications occur
      as mono-Ubl or poly-Ubl chains. Proteins that regulate poly-SUMO (small ubiquitin
      like modifier) chain conjugates play important roles in cellular response to DNA
      damage, such as those caused by cancer radiation therapy. Additionally, high
      atomic number metals, such as gold, preferentially absorb much more X-ray energy
      than soft tissues, and thus augment the effect of ionizing radiation when
      delivered to cells. In this study, we demonstrate that conjugation of a weak SUMO
      2/3 ligand to gold nanoparticles facilitated selective multivalent interactions
      with poly-SUMO-2/3 chains leading to efficient inhibition of poly-SUMO-chain
      mediated protein-protein interactions. The ligand-gold particle conjugate
      significantly sensitized cancer cells to radiation but was not toxic to normal
      cells. This study demonstrates a viable approach for selective targeting of poly
      Ubl chains through multivalent interactions created by nanoparticles that can be
      chosen based on their properties, such as abilities to augment radiation effects.

PMID- 22388746
TI  - Structure of a type III secretion needle at 7-A resolution provides insights into
      its assembly and signaling mechanisms.
AB  - Type III secretion systems of Gram-negative bacteria form injection devices that
      deliver effector proteins into eukaryotic cells during infection. They span both
      bacterial membranes and the extracellular space to connect with the host cell
      plasma membrane. Their extracellular portion is a needle-like, hollow tube that
      serves as a secretion conduit for effector proteins. The needle of Shigella
      flexneri is approximately 50-nm long and 7-nm thick and is made by the helical
      assembly of one protein, MxiH. We provide a 7-A resolution 3D image
      reconstruction of the Shigella needle by electron cryomicroscopy, which resolves
      alpha-helices and a beta-hairpin that has never been observed in the crystal and
      solution structures of needle proteins, including MxiH. An atomic model of the
      needle based on the 3D-density map, in comparison with that of the bacterial
      flagellar filament, provides insights into how such a thin tubular structure is
      stably assembled by intricate intermolecular interactions. The map also
      illuminates how the needle-length control protein functions as a ruler within the
      central channel during export of MxiH for assembly at the distal end of the
      needle, and how the secretion-activation signal may be transduced through a
      conformational change of the needle upon host-cell contact.

PMID- 22388747
TI  - Agonism/antagonism switching in allosteric ensembles.
AB  - Ligands for several transcription factors can act as agonists under some
      conditions and antagonists under others. The structural and molecular bases of
      such effects are unknown. Previously, we demonstrated how the folding of
      intrinsically disordered (ID) protein sequences, in particular, and population
      shifts, in general, could be used to mediate allosteric coupling between
      different functional domains, a model that has subsequently been validated in
      several systems. Here it is shown that population redistribution within
      allosteric systems can be used as a mechanism to tune protein ensembles such that
      a given ligand can act as both an agonist and an antagonist. Importantly, this
      mechanism can be robustly encoded in the ensemble, and does not require that the
      interactions between the ligand and the protein differ when it is acting either
      as an agonist or an antagonist. Instead, the effect is due to the relative
      probabilities of states prior to the addition of the ligand. The ensemble view of
      allostery that is illuminated by these studies suggests that rather than being
      seen as switches with fixed responses to allosteric activation, ensembles can
      evolve to be "functionally pluripotent," with the capacity to up or down regulate
      activity in response to a stimulus. This result not only helps to explain the
      prevalence of intrinsic disorder in transcription factors and other cell
      signaling proteins, it provides important insights about the energetic ground
      rules governing site-to-site communication in all allosteric systems.

PMID- 22388748
TI  - Structure and function of a serine carboxypeptidase adapted for degradation of
      the protein synthesis antibiotic microcin C7.
AB  - Several classes of naturally occurring antimicrobials exert their antibiotic
      activity by specifically targeting aminoacyl-tRNA synthetases, validating these
      enzymes as drug targets. The aspartyl tRNA synthetase "Trojan horse" inhibitor
      microcin C7 (McC7) consists of a nonhydrolyzable aspartyl-adenylate conjugated to
      a hexapeptide carrier that facilitates active import into bacterial cells through
      an oligopeptide transport system. Subsequent proteolytic processing releases the
      toxic compound inside the cell. Producing strains of McC7 must protect themselves
      against autotoxicity that may result from premature processing. The mccF gene
      confers resistance against endogenous and exogenous McC7 by hydrolyzing the amide
      bond that connects the peptide and nucleotide moieties of McC7. We present here
      crystal structures of MccF, in complex with various ligands. The MccF structure
      is similar to that of dipeptide ld-carboxypeptidase, but with an additional loop
      proximal to the active site that serves as the primary determinant for
      recognition of adenylated substrates. Wild-type MccF only hydrolyzes the
      naturally occurring aspartyl phosphoramidate McC7 and synthetic peptidyl
      sulfamoyl adenylates that contain anionic side chains. We show that substitutions
      of two active site MccF residues result in a specificity switch toward aromatic
      aminoacyl-adenylate substrates. These results suggest how MccF-like enzymes may
      be used to avert various toxic aminoacyl-adenylates that accumulate during
      antibiotic biosynthesis or in normal metabolism of the cell.

PMID- 22388749
TI  - Rapid diversification of coevolving marine Synechococcus and a virus.
AB  - Marine viruses impose a heavy mortality on their host bacteria, whereas at the
      same time the degree of viral resistance in marine bacteria appears to be high.
      Antagonistic coevolution--the reciprocal evolutionary change of interacting
      species--might reconcile these observations, if it leads to rapid and dynamic
      levels of viral resistance. Here we demonstrate the potential for extensive
      antagonistic coevolution between the ecologically important marine cyanobacterium
      Synechococcus and a lytic virus. In a 6-mo-long replicated chemostat experiment,
      Synechococcus sp. WH7803 and the virus (RIM8) underwent multiple coevolutionary
      cycles, leading to the rapid diversification of both host and virus. Over the
      course of the experiment, we detected between 4 and 13 newly evolved viral
      phenotypes (differing in host range) and between 4 and 11 newly evolved
      Synechococcus phenotypes (differing in viral resistance) in each chemostat.
      Genomic analysis of isolates identified several candidate genes in both the host
      and virus that might influence their interactions. Notably, none of the viral
      candidates were tail fiber genes, thought to be the primary determinants of host
      range in tailed bacteriophages, highlighting the difficulty in generalizing
      results from bacteriophage infecting gamma-Proteobacteria. Finally, we show that
      pairwise virus-host coevolution may have broader community consequences;
      coevolution in the chemostat altered the sensitivity of Synechoccocus to a
      diverse suite of viruses, as well as the virus' ability to infect additional
      Synechococcus strains. Our results indicate that rapid coevolution may contribute
      to the generation and maintenance of Synechococcus and virus diversity and
      thereby influence viral-mediated mortality of these key marine bacteria.

PMID- 22388750
TI  - GFR estimation in the morbidly obese pre- and postbariatric surgery: one size
      does not fit all.
AB  - BACKGROUND: Glomerular hyperfiltration commonly associated with obesity is
      expected to improve postbariatric surgery. However, formula-based glomerular
      filtration rate (GFR) estimation in these patients is limited by body size
      confounders necessitating use of modified equations, the reliability of which
      remains uncertain. METHODS: In this study, various GFR-estimating formulae were
      compared in morbidly obese patients at baseline and postbariatric surgery.
      Through a retrospective chart review, we identified 220 patients who had
      undergone this procedure, with over 6-month follow-up, during which major weight
      reduction was achieved. RESULTS: A significant decrease in BP and glomerular
      hyperfiltration was observed, though there was large variability in GFR
      estimation using the different formulae. Gross over and underestimation was
      observed which improved with correction for body size confounders especially lean
      body weight (LBW). Postoperatively, significant attenuation in estimated GFR was
      demonstrated when LBW or body surface area-adjusted versions were used. In a
      subgroup of patients with chronic kidney disease, a significant improvement in
      GFR was seen postoperatively with the LBW-modified formula but there were again
      inconsistencies when using other equations. CONCLUSION: Though clinicians must be
      critical in the application of GFR estimates to patient care, LBW adjustment
      appears to be the most practical solution to its estimation in the obese
      patients. This is particularly true for patients with normal renal function but
      appears to be also applicable to those with compromised kidney function. Future
      studies are needed to compare these equations with a gold standard GFR measure as
      well as to explore whether the renal benefits from bariatric surgery are
      sustained or seen in more advanced CKD stages.

PMID- 22388751
TI  - Use of peritoneal ultrafiltration in the elderly refractory congestive heart
      failure patients.
AB  - BACKGROUND: Refractory congestive heart failure (RCHF), due to its high mortality
      and hospitalization rates, is a growing health problem. In this study, as an
      alternative and/or supportive treatment to conventional medical therapies, we
      have evaluated the clinical value of peritoneal ultrafiltration, performed as a
      single daily exchange with icodextrin or conventional dextrose-based peritoneal
      dialysis solutions, in elderly patients with RCHF. METHODS: This was an
      observational study of 6 elderly patients with RCHF and non-terminal chronic
      kidney disease (CKD). Their mean age was 72.8 +/- 4.9 years. Four of the six
      patients had NYHA class 4 and two had NYHA class 3 RCHF and a medical history of
      18.6 +/- 14.9 days/year hospitalization on average, due to decompensated
      congestive heart failure (CHF). Their baseline glomerular filtration rate, as
      calculated by the MDRD formula was 49.4 +/- 14.6 mL/min/1.73 m(2). During
      hospitalization, patients were initially treated with several sessions of
      continuous veno-venous hemofiltration and, following the achievement of
      hemodynamic stabilization, peritoneal ultrafiltration was initiated as the
      maintenance ultrafiltration modality. Patients were followed up monthly in terms
      of their clinical status, hospitalization rates, weight changes, serum sodium
      levels, and renal function. Echocardiographic changes were also evaluated every 3
      months. RESULTS: All patients tolerated peritoneal ultrafiltration well, their
      functional status improved by 1 or 2 NYHA classes to reach a mean of NYHA class 2
      CHF status. During the follow-up period, with a mean daily ultrafiltration rate
      of 850 +/- 176 mL, no hospitalization for decompensated CHF or acute renal
      failure was required. The patients' renal function was well preserved, with a
      mean GFR of 49 +/- 14.6 mL/min/1.73 m(2) at baseline and 51.6 +/- 22.9
      mL/min/1.73 m(2) at the 6th month of the study. Additionally, their mean serum
      sodium levels increased from 128 +/- 5.7 mEq/L to 138 +/- 5 mEq/L.
      Echocardiographic evaluation did not show any significant changes during the
      observation period. No peritonitis or other non-infectious complication of
      chronic peritoneal dialysis was seen in any of the patients. CONCLUSIONS:
      Peritoneal ultrafiltration seems to be an efficient and safe procedure and a
      treatment of choice in elderly patients with RCHF without non-terminal CKD.
      Peritoneal ultrafiltration improves the quality of life and the effort capacity,
      and reduces hospitalization rates due to decompensated heart failure and acute
      renal failure.

PMID- 22388753
TI  - Comments to the article by Wu: Retrograde dynamic locked nailing for valgus knee
      correction: a revised technique.

PMID- 22388752
TI  - Pre- and postnatal calorie restriction perturbs early hypothalamic neuropeptide
      and energy balance.
AB  - Energy balance is regulated by circulating leptin concentrations and hypothalamic
      leptin receptor (ObRb) signaling via STAT3 but is inhibited by SOCS3 and PTP1B.
      Leptin signaling enhances anorexigenic neuropeptides and receptor (POMC, MC3-R,
      MC4-R) activation while suppressing orexigenic neuropeptides (NPY, AgRP). We
      investigated in a sex-specific manner the early (PN2) and late (PN21) postnatal
      hypothalamic mechanisms in response to intrauterine (IUGR), postnatal (PNGR), and
      combined (IPGR) calorie and growth restriction. At PN2, both male and female IUGR
      were hypoleptinemic, but hypothalamic leptin signaling in females was activated
      as seen by enhanced STAT3. In addition, increased SOCS3 and PTP1B supported early
      initiation of leptin resistance in females that led to elevated AgRP but
      diminished MC3-R and MC4-R. In contrast, males demonstrated leptin sensitivity
      seen as a reduction in PTP1B and MC3-R and MC4-R with no effect on neuropeptide
      expression. At PN21, with adequate postnatal caloric intake, a sex-specific
      dichotomy in leptin concentrations was seen in IUGR, with euleptinemia in males
      indicative of persisting leptin sensitivity and hyperleptinemia in females
      consistent with leptin resistance, both with normal hypothalamic ObRb signaling,
      neuropeptides, and energy balance. In contrast, superimposition of PNGR upon IUGR
      (IPGR) led to diminished leptin concentrations with enhanced PTP1B and an
      imbalance in arcuate nuclear NPY/AgRP and POMC expression that favored
      exponential hyperphagia and diminished energy expenditure postweaning. We
      conclude that IUGR results in sex-specific leptin resistance observed mainly in
      females, whereas PNGR and IPGR abolish this sex-specificity, setting the stage
      for acquiring obesity after weaning.

PMID- 22388754
TI  - Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a
      clinicopathologic spectrum similar to cutaneous CD30-positive T-cell
      lymphoproliferative disorders.
AB  - CD30-positive T-cell lymphoproliferative disorders are classified as cutaneous
      (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) or
      systemic. As extent of disease dictates prognosis and treatment, patients with
      skin involvement need clinical staging to determine whether systemic lymphoma
      also is present. Similar processes may involve mucosal sites of the head and
      neck, constituting a spectrum that includes both neoplasms and reactive
      conditions (eg, traumatic ulcerative granuloma with stromal eosinophilia).
      However, no standard classification exists for mucosal CD30-positive T-cell
      lymphoproliferations. To improve our understanding of these processes, we
      identified 15 such patients and examined clinical presentation, treatment and
      outcome, morphology, phenotype using immunohistochemistry, and genetics using
      gene rearrangement studies and fluorescence in situ hybridization. The 15
      patients (11 M, 4 F; mean age, 57 years) had disease involving the oral
      cavity/lip/tongue (9), orbit/conjunctiva (3) or nasal cavity/sinuses (3). Of 14
      patients with staging data, 7 had mucosal disease only; 2 had mucocutaneous
      disease; and 5 had systemic anaplastic large cell lymphoma. Patients with mucosal
      or mucocutaneous disease only had a favorable prognosis and none developed
      systemic spread (follow-up, 4-93 months). Three of five patients with systemic
      disease died of lymphoma after 1-48 months. Morphologic and phenotypic features
      were similar regardless of extent of disease. One anaplastic lymphoma kinase
      positive case was associated with systemic disease. Two cases had rearrangements
      of the DUSP22-IRF4 locus on chromosome 6p25.3, seen most frequently in primary
      cutaneous anaplastic large cell lymphoma. Our findings suggest mucosal CD30
      positive T-cell lymphoproliferations share features with cutaneous CD30-positive
      T-cell lymphoproliferative disorders, and require clinical staging for
      stratification into primary and secondary types. Primary cases have
      clinicopathologic features closer to primary cutaneous disease than to systemic
      anaplastic large cell lymphoma, including indolent clinical behavior.
      Understanding the spectrum of mucosal CD30-positive T-cell lymphoproliferations
      is important to avoid possible overtreatment resulting from a diagnosis of overt
      T-cell lymphoma.

PMID- 22388755
TI  - Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of
      pancreatic origin.
AB  - Neuroendocrine tumors can present as liver metastases before discovery of the
      primary tumor. Islet 1 and PAX8 have recently been proposed as markers for
      neuroendocrine tumors of pancreatic origin. In this study, we compared the
      utility of Islet 1 and PAX8 in distinguishing pancreatic neuroendocrine tumors
      from neuroendocrine tumors of other sites and determined the usefulness of an
      immunohistochemical panel, including TTF1, CDX2, Islet 1 and/or PAX8, in
      identifying metastatic pancreatic neuroendocrine tumors. A total of 110 primary
      neuroendocrine tumors (33 pancreatic, 31 pulmonary, 23 ileal, 14 rectal, and 9
      gastric) and 73 metastatic neuroendocrine tumors (28 pancreatic, 5 pulmonary, 37
      ileal, 1 rectal, 1 colonic, and 1 duodenal) were studied. Islet 1 and PAX8 were
      positive in 27/33 (82%) and 29/33 (88%), respectively, of primary pancreatic
      neuroendocrine tumors, and in 19/28 (68%) and 15/28 (54%), respectively, of
      metastatic pancreatic neuroendocrine tumors. No cases of primary (0/23) or
      metastatic (0/37) ileal neuroendocrine tumors were positive with either Islet 1
      or PAX8. There was Islet 1 positivity in 2/31 (6%) primary pulmonary, 12/14 (86%)
      primary rectal, and 1/1 metastatic rectal neuroendocrine tumors, and PAX8
      positivity in 7/31 (23%) primary pulmonary, 11/14 (79%) primary rectal, and 2/9
      (22%) primary gastric neuroendocrine tumors. ROC curve analysis incorporating
      sensitivity and specificity data of immunohistochemical panels for metastatic
      pancreatic neuroendocrine tumors showed that a four-stain panel, including Islet
      1, PAX8, TTF1, and CDX2 significantly outperformed a three-stain panel composed
      of PAX8, TTF1, and CDX2 (P=0.019), and also showed a trend for better performance
      compared with a three-stain panel composed of Islet 1, TTF1, and CDX2 (P=0.072).
      Both Islet 1 and PAX8 are reliable immunohistochemical markers for pancreatic
      neuroendocrine tumors and would be useful adjuncts to other markers (TTF1, CDX2)
      currently used to work up a metastatic neuroendocrine tumor of unknown primary.

PMID- 22388756
TI  - FUS rearrangements are rare in 'pure' sclerosing epithelioid fibrosarcoma.
AB  - Several recent reports have described low-grade fibromyxoid sarcoma with
      sclerosing epithelioid fibrosarcoma-like areas. We evaluated cases of pure
      sclerosing epithelioid fibrosarcoma lacking areas of low-grade fibromyxoid
      sarcoma for FUS rearrangement to determine whether this entity could be related
      to low-grade fibromyxoid sarcoma. Available formalin-fixed paraffin-embedded
      tissue of 27 sclerosing epithelioid fibrosarcoma from 25 patients was retrieved
      and tabulated with clinical information. Unstained slides from formalin-fixed
      paraffin-embedded blocks were prepared and fluorescence in-situ hybridization was
      performed using a commercial FUS break-apart probe. The median patient age at
      presentation was 50 (range, 14-78) years, with 14 males and 10 females.
      Sclerosing epithelioid fibrosarcoma most commonly involved the extremities (n=8)
      or chest (n=6). Sixteen patients had a median follow-up of 17 (range, 1-99)
      months; seven were alive and well at 12 (range, 5-30) months; three alive with
      disease at 28 (range, 9-99) months; five dead of disease at a median of 22
      (range, 1-36) months and one was dead of unknown causes. Twelve patients were
      known to have metastases; the most common site was lung (n=7), followed by bone
      (n=3), lymph nodes (n=2) and peritoneum (n=1). Only 2 of 22 (9%) analyzable cases
      of sclerosing epithelioid fibrosarcoma showed rearrangement in the FUS locus by
      fluorescence in-situ hybridization. Although cytogenetically confirmed low-grade
      fibromyxoid sarcoma can have sclerosing epithelioid fibrosarcoma-like areas, FUS
      rearrangement, which is characteristic of low-grade fibromyxoid sarcoma, appears
      to be relatively rare in pure sclerosing epithelioid fibrosarcoma.

PMID- 22388757
TI  - Stem cell-related markers in primary breast cancers and associated metastatic
      lesions.
AB  - It has been reported previously that: (1) normal-breast epithelial cells that are
      CD24-/44+ express higher levels of stem/progenitor cell-associated genes; (2)
      cancer cells that have undergone epithelial to mesenchymal transition display
      CD24-/44+ cell-surface expression, a marker for breast cancer stem cells; (3)
      loss of E-cadherin is a preliminary step in epithelial to mesenchymal transition;
      and (4) vimentin is a marker of mesenchymal phenotype. We hypothesized that stem
      cell subpopulations would be more frequent in metastatic than in primary tumors.
      Therefore we assessed by immunohistochemical analysis, tissue microarrays
      containing tissue from primary and associated metastatic breast cancers for
      expression of CD24, CD44, E-cadherin and vimentin to evaluate candidate cancer
      initiating cell populations in breast cancer subtypes and metastatic lesions. The
      occurrence of CD24-/44+ and CD24+/44- cells did not differ in primary vs matched
      lymph node or distant and locoregional metastatic lesions; E-cadherin expression
      was decreased in primary vs lymph node metastases (P=0.018) but not decreased in
      distant and locoregional metastases relative to primary tumor, whereas vimentin,
      was more frequently expressed in lymph node and distant and locoregional
      metastases (P=0.013, P=0.004) than in matched primary cancers. Thus, the
      frequency of CD24-/44+ cells does not differ in metastases relative to the
      primary breast cancer but differs by tumor stage and subtype.

PMID- 22388758
TI  - The molecular basis of EPCAM expression loss in Lynch syndrome-associated tumors.
AB  - Germline deletions affecting the epithelial cell adhesion molecule (EPCAM) gene
      lead to silencing of MSH2 and cause Lynch syndrome. We have recently reported
      that lack of EPCAM expression occurs in many, but not all tumors from Lynch
      syndrome patients with EPCAM germline deletions. The differences in EPCAM
      expression were not related to the localization of EPCAM germline deletions. We
      therefore hypothesized that the type of the second somatic hit, which leads to
      MSH2 inactivation during tumor development, determines EPCAM expression in the
      tumor cells. To test this hypothesis and to evaluate whether lack of EPCAM
      expression can already be detected in Lynch syndrome-associated adenomas, we
      analyzed four carcinomas and two adenomas from EPCAM germline deletion carriers
      for EPCAM protein expression and allelic deletion status of the EPCAM gene region
      by multiplex ligation-dependent probe amplification. In four out of six tumors we
      observed lack of EPCAM expression accompanied by biallelic deletions affecting
      the EPCAM gene. In contrast, monoallelic retention of the EPCAM gene was observed
      in the remaining two tumors with retained EPCAM protein expression. These results
      demonstrate that EPCAM expression in tumors from EPCAM deletion carriers depends
      on the localization of the second somatic hit that inactivates MSH2. Moreover, we
      report lack of EPCAM protein expression in a colorectal adenoma, suggesting that
      EPCAM immunohistochemistry may detect EPCAM germline deletions already at a
      precancerous stage.

PMID- 22388759
TI  - Histological and genetic evidence for a variant of superficial spreading melanoma
      composed predominantly of large nests.
AB  - Cutaneous melanomas are characterized by a range of histological appearances, and
      several morphological variants have been described. In this study, we report a
      variant of superficial spreading melanoma that is characterized by large,
      irregular junctional melanocytic nests. The junctional nests varied in shape and
      size, showed focal tendency to confluence, and were often surrounded by a cuff of
      epidermal keratinocytes. The melanocytes comprising the nests showed variable
      cytological atypia. In most of the cases, scant intraepidermal or junctional
      single melanocytes were seen, and other well-documented diagnostic criteria for
      melanoma were lacking, and as a result, histological recognition of these tumors
      as melanoma was difficult. Some cases were associated with an invasive dermal
      component or showed evidence of sun damage. To provide supporting evidence for
      malignancy, we analyzed these tumors for genomic aberrations. Using array
      comparative genomic hybridization (aCGH), we identified multiple genomic
      aberrations in all analyzed cases. A similar pattern of genomic aberrations was
      seen in a control group of bona fide superficial spreading melanomas, suggesting
      that these 'melanomas composed exclusively or predominantly of large nests' are
      indeed variants of superficial spreading melanoma. Fluorescence in-situ
      hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the
      FISH-negative cases showed multiple genomic aberrations in regions that are not
      covered by FISH. The low sensitivity of the FISH test can be explained by the
      fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH
      surveys the entire genome. In summary, we present histological and molecular
      genetic evidence for a morphological variant of superficial spreading melanoma.
      Awareness of the histological features will aid in their correct diagnosis as
      melanoma, and in difficult cases, judicious application of ancillary tests such
      as aCGH (rather than FISH) will assist accurate diagnosis.

PMID- 22388760
TI  - Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its
      clinicopathological significance.
AB  - Intratumoral heterogeneity of human epidermal growth factor receptor 2 (HER2)
      gene amplification has been reported to occur with variable frequencies in breast
      cancers. However, there have been few studies of its clinicopathological
      significance. We used tissue microarrays to evaluate two aspects of intratumoral
      heterogeneity of HER2 gene amplification: regional heterogeneity and genetic
      heterogeneity. We examined 96 invasive breast cancers in which HER2 amplification
      had been diagnosed in whole sections, and determined the clincopathological
      characteristics of those tumors. HER2 regional heterogeneity, defined as the
      existence of amplification/negative or amplification/equivocal patterns in
      different tissue microarray cores of a tumor, was present in 17 (18%) of the 96
      cases. HER2 genetic heterogeneity, defined as the presence of tumor cells with a
      HER2/chromosome enumeration probe 17 ratio higher than 2.2 in 5-50% of the tumor
      cells, was found in 11 cases (11%), all of which showed HER2 regional
      heterogeneity. The cases with intratumoral heterogeneity of HER2 gene
      amplification were characterized by low grade or equivocal HER2 amplification and
      equivocal (2+) HER2 expression in whole sections. The patients with intratumoral
      heterogeneity of HER2 gene amplification had significantly shorter disease-free
      survival times than those with homogeneous HER2 gene amplification, and this
      effect was also evident in subgroup analysis by hormone receptor status. In
      multivariate analysis, intratumoral HER2 heterogeneity retained its status as an
      independent prognostic factor for disease-free survival. In conclusion,
      intratumoral heterogeneity of HER2 gene amplification is present in a subset of
      HER2-amplified breast cancers, especially in cases with low-grade HER2
      amplification and equivocal HER2 expression, indicating a need for HER2 testing
      on more representative, larger tumor samples for accurate assessment of HER2
      status in such cases. The patients with this heterogeneity have decreased disease
      free survival, suggesting that genetic instability, and hence aberrant HER2
      amplification in subclones of such tumors, may be associated with breast cancer
      progression.

PMID- 22388761
TI  - NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors:
      significance for NY-ESO-1-based targeted therapy and differential diagnosis.
AB  - A promising targeted therapy against NY-ESO-1 (CTAG 1B) using genetically
      modified T-cells in synovial sarcomas was recently demonstrated in a clinical
      trial at the NCI. To investigate the role of NY-ESO-1 immunohistochemistry in
      patient selection and gain better insight into the incidence of NY-ESO-1
      expression in synovial sarcomas and other mesenchymal tumors, we evaluated NY-ESO
      1 expression by immunohistochemistry in 417 tumors. This collection of samples
      included: 50 SS18/SSX1/2 fusion positive synovial sarcomas, 155 gastrointestinal
      stromal tumors (GIST), 135 other spindle cell sarcomas as well as 77 other
      sarcomas (chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma, alveolar
      soft part sarcoma, rhabdomyosarcoma, angiosarcoma, malignant mesothelioma, and
      Ewing's sarcoma). We report that 76% of synovial sarcomas expressed NY-ESO-1 in a
      strong and diffuse pattern (2-3+, >50-70% of tumor cells). In contrast, only rare
      cases of other spindle cell mesenchymal tumor expressed NY-ESO-1 (GIST (2/155),
      malignant peripheral nerve sheath tumors (1/34), and dermatofibrosarcoma
      protuberans (2/20)). Individual cases of other sarcomas (angiosarcoma, malignant
      mesothelioma, chondrosarcoma, osteosarcoma, dedifferentiated liposarcoma,
      alveolar soft part sarcoma, and Ewing's sarcoma) were positive for NY-ESO-1.
      However, no positive cases were identified amongst our cohort of leiomyosarcomas
      (0/24), hemangiopericytoma/solitary fibrous tumors (0/40), and cellular
      schwannomas (0/17). In summary, we find that NY-ESO-1 is strongly and diffusely
      expressed in a majority of synovial sarcomas, but only rarely in other
      mesenchymal lesions. Beyond its role in patient selection for targeted therapy,
      immunohistochemistry for NY-ESO-1 may be diagnostically useful for the
      distinction of synovial sarcoma from other spindle cell neoplasms.

PMID- 22388762
TI  - Pleomorphic mesothelioma: report of 10 cases.
AB  - Mesotheliomas with pleomorphic features are rare and only a few studies on this
      mesothelioma variant have been published. Little information regarding the
      immunoprofile of these tumors and none on their electron microscopic features was
      included in these studies. Herein are reported 10 cases of pleomorphic
      mesothelioma that were investigated using a large panel of immunohistochemical
      markers, 4 of which were also studied by electron microscopy. All of the patients
      were men and seven had a history of asbestos exposure. Nine of the cases
      originated in the pleura and one in the peritoneum. Histologically, the tumors
      were characterized by being composed of large, often discohesive, cells that
      varied in size and shape, had dense abundant eosinophilic cytoplasm, and single
      or multiple irregular nuclei, which often contained one or several large
      nucleoli. Mitotic activity was high and atypical mitoses frequent.
      Immunoreactivity for pan-keratin and keratin 7 was strong in all of the cases.
      Expression for calretinin, WT1, podoplanin, mesothelin and keratin 5/6 was also
      frequent, but variable. All cases were negative for MOC-31, carcinoembryonic
      antigen, CD15, TAG-72 and thyroid transcription factor-1. Electron microscopy
      often showed the presence of abundant long, slender microvilli on the cell
      membrane of the neoplastic cells. These findings demonstrate that, contrary to
      what has been suggested by some investigators, both immunohistochemistry and
      electron microscopy can be very helpful in assisting in the diagnosis of
      pleomorphic mesotheliomas. That the seven patients who underwent extrapleural
      pneumonectomy had extensive lymph node metastasis and that the median survival of
      those patients for whom follow-up information was available was only 8.2 months
      indicates that mesotheliomas with pleomorphic features are associated with highly
      aggressive clinical behavior. Therefore, when this subtype of epithelioid
      mesothelioma is present, it should be reported as it can significantly affect the
      prognosis and treatment of the patient.

PMID- 22388763
TI  - Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome
      negative myeloproliferative neoplasms: heterogeneous morphology and cytological
      composition.
AB  - We studied 24 spleens with extramedullary hematopoietic proliferation (EMHP), a
      key feature of advanced-stage Philadelphia chromosome-negative myeloproliferative
      neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia
      vera and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome
      stains, and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b,
      CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were
      evaluated. Clinical information was correlated with the morphological findings.
      Three distinct histological patterns of EMHP were recognized: diffuse (12),
      nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was
      granulocytic in diffuse, trilineage in nodular and erythroid in mixed EMHP.
      Erythropoiesis was largely intravascular, granulopoiesis was within the splenic
      cords and megakaryopoiesis was observed in both locations. The stromal changes
      paralleled the histological pattern with preservation of the splenic stromal and
      vascular architecture in the diffuse areas as opposed to areas of nodular EMHP.
      The morphological features of the splenic EMHP did not correlate with specific
      subtypes of myeloproliferative neoplasms. The mean duration of follow-up from
      initial diagnosis was 80 months. A total of 15 of the 24 patients died of
      disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%)
      with mixed growth patterns. The mean duration from diagnosis to splenectomy was
      shorter in patients with diffuse (83 months) as compared with those with nodular
      EMHP (127 months). Our study demonstrates that splenic extramedullary
      hematopoietic proliferation in Philadelphia chromosome-negative
      myeloproliferative neoplasms shows distinct histological patterns that do not
      correlate with disease subtypes, but appear to suggest a trend between the
      histological patterns and clinical behavior. These results suggest a different
      biology of the disease in the nodular and diffuse extramedullary hematopoietic
      proliferation groups.

PMID- 22388764
TI  - Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological
      and immunohistochemical study of five cases.
AB  - Five cases of an unusual variant of thymic carcinoma are described, which
      represent the counterpart of the so-called micronodular thymoma with lymphoid
      hyperplasia. The patients were three men and two women aged 42-78 years (mean 64
      years). Three patients were asymptomatic and the tumors were found incidentally
      on chest radiographs performed for unrelated reasons. Two patients complained of
      dyspnea, chest pain and shortness of breath prompting further investigations. The
      tumors ranged in size from 3.2 to 10.0 cm and were described as infiltrative
      masses often invading adjacent structures. Prominent cystic changes were not
      identified. Histologically, the neoplasms were composed of epithelial tumor cells
      arranged in a micronodular growth pattern set in a stroma showing florid lymphoid
      hyperplasia. Contrary to micronodular thymoma, the epithelial cell component of
      the present cases showed unequivocal signs of malignancy characterized by
      cytological atypia and increased mitotic activity. Immunohistochemical studies
      showed the lymphoid component to be of mixed B- and T-cell lineage. None of the
      patients had a history of myasthenia gravis or other autoimmune disorder. Follow
      up revealed that 4 patients were alive and well 3-26 months after diagnosis while
      1 patient was dead of disease 21 months after diagnosis. The tumors in this
      series represent a distinct subtype of thymic carcinoma histologically strongly
      resembling micronodular thymoma with lymphoid hyperplasia. Awareness of this type
      of thymic carcinoma is important in order not to dismiss this tumor for a
      neoplasm of lower-grade malignancy.

PMID- 22388765
TI  - Genetic susceptibility to burnout in a Swedish twin cohort.
AB  - Most previous studies of burnout have focused on work environmental stressors,
      while familial factors so far mainly have been overlooked. The aim of the study
      was to estimate the relative importance of genetic influences on burnout
      (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and
      dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals,
      born 1959-1986 from the Swedish twin registry who participated in the cross
      sectional study of twin adults: genes and environment. Probandwise concordance
      rates (the risk for one twin to be affected given that his/her twin partner is
      affected by burnout) and within pair correlations were calculated for MZ and DZ
      same--and opposite sexed twin pairs. Heritability coefficients i.e. the
      proportion of the total variance attributable to genetic factors were calculated
      using standard biometrical model fitting procedures. The results showed that
      genetic factors explained 33% of the individual differences in burnout symptoms
      in women and men. Environmental factors explained a substantial part of the
      variation as well and are thus important to address in rehabilitation and
      prevention efforts to combat burnout.

PMID- 22388766
TI  - A genetic instrument for Mendelian randomization of fibrinogen.
AB  - Mendelian randomization studies on fibrinogen commonly use a single genetic
      variant as an instrument, but this may explain only a small proportion of the
      total phenotypic variance. We examined the contribution of multiple common single
      nucleotide polymorphisms (SNPs) and haplotypes in the entire fibrinogen gene
      cluster to plasma fibrinogen levels in two prospective cohorts, for use as
      instruments in future Mendelian randomization studies. Genotypes for 20 SNPs were
      determined in 2,778 middle-age (49-64 years) men from the Second-Northwick-Park
      Heart Study (NPHS-II). These were replicated in 3,705 men from the Whitehall-II
      study (WH-II). Plasma fibrinogen levels were determined six times in NPHS-II and
      three times in WH-II. The minor alleles of four SNPs from the FGB gene, two from
      the FGA gene, and one from the FGG gene were associated with higher plasma
      fibrinogen levels. SNP rs1800790 (-455G>A) commonly used in Mendelian
      randomization studies was associated with R2=1.22% of the covariate adjusted
      residual variance in fibrinogen level. A variable selection procedure identified
      one additional SNP: rs2070011 (FGA) altogether explaining R2=1.45% of the
      residual variance in fibrinogen level. Using these SNPs no evidence for causality
      between the fibrinogen levels and coronary heart diseases was found in
      instrumental variables analysis. In the replication cohort, WH-II, the effects of
      the two SNPs on fibrinogen levels were consistent with the NPHS-II results. There
      is statistical evidence for several functional sites in the fibrinogen gene
      cluster that determine an individual's plasma fibrinogen levels. Thus, a
      combination of several SNPs will provide a stronger instrument for fibrinogen
      Mendelian randomization studies.

PMID- 22388767
TI  - Methods of data collection and definitions of cardiac outcomes in the Rotterdam
      Study.
AB  - The prevalence of cardiovascular diseases is rising. Therefore, adequate risk
      prediction and identification of its determinants is increasingly important. The
      Rotterdam Study is a prospective population-based cohort study ongoing since 1990
      in the city of Rotterdam, The Netherlands. One of the main targets of the
      Rotterdam Study is to identify the determinants and prognosis of cardiovascular
      diseases. Case finding in epidemiological studies is strongly depending on
      various sources of follow-up and clear outcome definitions. The sources used for
      collection of data in the Rotterdam Study are diverse and the definitions of
      outcomes in the Rotterdam Study have changed due to the introduction of novel
      diagnostics and therapeutic interventions. This article gives the methods for
      data collection and the up-to-date definitions of the cardiac outcomes based on
      international guidelines, including the recently adopted cardiovascular disease
      mortality definitions. In all, detailed description of cardiac outcome
      definitions enhances the possibility to make comparisons with other studies in
      the field of cardiovascular research and may increase the strength of
      collaborations.

PMID- 22388768
TI  - Repeated measures of body mass index and risk of health related outcomes.
AB  - Most studies examining the association between body mass index (BMI) and
      mortality neglected changes in weight over time, which may have led to
      underestimation of the true association. The aim of this study is to examine the
      relationship between BMI and health related outcomes while accounting for
      variations of BMI over time. The association between BMI and both mortality and
      occupational disability was examined in a follow-up of 5,554 male construction
      workers in Wurttemberg/Germany, who participated at least two times in routine
      occupational health examinations between 1986 and 2005. Using Cox proportional
      hazards model with time dependent variables, hazard ratios were calculated with
      normal weight (<25 kg/m2) as reference after adjustment for potential confounding
      factors. Overall, an U-shaped association between baseline BMI and mortality (370
      events) as well as occupational disability (658 events) was observed, with lowest
      risk at BMI levels between 25 and 30 kg/m2. Men with a baseline BMI >= 30 kg/m2
      experienced a 10% higher mortality and disability risk than normal weight men.
      The association between BMI and occupational disability became stronger after
      accounting for temporal variability of BMI with a significant increased risk of
      1.26 (95% confidence interval: 1.01-1.56) among obese men. In contrast, the
      association between BMI and mortality did not materially change after accounting
      for time dependent effects. Stable obesity as defined by a BMI of 30 kg/m2 and
      above increases risk of disability in male construction workers. Accounting for
      changes of BMI over time is crucial for disclosing full impact of obesity.

PMID- 22388769
TI  - Enantioenrichment in sublimed amino acid mixtures.
AB  - A real amplification of an initial enantiomeric excess can be detected when two
      amino acids are sublimed at high temperature, even if one of the components is a
      racemic compound that does not convert into a conglomerate by sublimation.

PMID- 22388770
TI  - Shape-controllable microlens arrays via direct transfer of photocurable polymer
      droplets.
AB  - A simple method is presented to form an array of shape-controllable microlenses
      by partial photocuring of an UV-curable polymer and direct transfer. Using the
      transferred lens array, nanoscale metal patterns as small as 130-nm gaps are
      detected under an optical microscope with a distinguishable resolution.

PMID- 22388771
TI  - Risk of death or life-threatening injury for women with children not sired by the
      abuser.
AB  - Women who are abused by their male intimate partners incur many costs, ranging in
      severity from fleeting physical pain to death. Previous research has linked the
      presence of children sired by a woman's previous partner to increased risk of
      woman abuse and to increased risk of femicide. The current research extends this
      work by securing data from samples of 111 unabused women, 111 less severely
      abused women, 128 more severely abused women, and 26 victims of intimate partner
      femicide from the Chicago Women's Health Risk Study to document an ordinal trend
      in the risk of experiencing more severe forms of violence for women who have
      children in the household sired by a previous partner. The discussion addresses
      two potential explanations for this trend and highlights directions for future
      research.

PMID- 22388772
TI  - Sexual size dimorphism, canine dimorphism, and male-male competition in primates:
      where do humans fit in?
AB  - Sexual size dimorphism is generally associated with sexual selection via
      agonistic male competition in nonhuman primates. These primate models play an
      important role in understanding the origins and evolution of human behavior.
      Human size dimorphism is often hypothesized to be associated with high rates of
      male violence and polygyny. This raises the question of whether human dimorphism
      and patterns of male violence are inherited from a common ancestor with
      chimpanzees or are uniquely derived. Here I review patterns of, and causal models
      for, dimorphism in humans and other primates. While dimorphism in primates is
      associated with agonistic male mate competition, a variety of factors can affect
      male and female size, and thereby dimorphism. The causes of human sexual size
      dimorphism are uncertain, and could involve several non-mutually-exclusive
      mechanisms, such as mate competition, resource competition, intergroup violence,
      and female choice. A phylogenetic reconstruction of the evolution of dimorphism,
      including fossil hominins, indicates that the modern human condition is derived.
      This suggests that at least some behavioral similarities with Pan associated with
      dimorphism may have arisen independently, and not directly from a common
      ancestor.

PMID- 22388773
TI  - Intergroup aggression in chimpanzees and war in nomadic hunter-gatherers:
      evaluating the chimpanzee model.
AB  - Chimpanzee and hunter-gatherer intergroup aggression differ in important ways,
      including humans having the ability to form peaceful relationships and alliances
      among groups. This paper nevertheless evaluates the hypothesis that intergroup
      aggression evolved according to the same functional principles in the two species
      selection favoring a tendency to kill members of neighboring groups when killing
      could be carried out safely. According to this idea chimpanzees and humans are
      equally risk-averse when fighting. When self-sacrificial war practices are found
      in humans, therefore, they result from cultural systems of reward, punishment,
      and coercion rather than evolved adaptations to greater risk-taking. To test this
      "chimpanzee model," we review intergroup fighting in chimpanzees and nomadic
      hunter-gatherers living with other nomadic hunter-gatherers as neighbors. Whether
      humans have evolved specific psychological adaptations for war is unknown, but
      current evidence suggests that the chimpanzee model is an appropriate starting
      point for analyzing the biological and cultural evolution of warfare.

PMID- 22388774
TI  - Highly efficient asymmetric Michael addition of aldehyde to nitroolefin using
      perhydroindolic acid as a chiral organocatalyst.
AB  - Perhydroindolic acids, the by-products obtained in the industrial production of a
      trandolapril intermediate, were used as chiral organocatalysts in asymmetric
      Michael addition reactions of aldehydes to nitroolefins. These proline-like
      catalysts are unique for their rigid bicyclic structure with two H atoms attached
      to the bridgehead C atoms lying on the opposite side of the ring. They therefore
      showed high efficiency in asymmetric Michael additions of aldehydes to
      nitroolefins. Under the optimal conditions, excellent diastereo- and
      enantioselectivities (up to 99/1 dr and 98% ee) were obtained with high chemical
      yields for a series of aldehydes and nitroolefins using only 5 mol% catalyst
      loading. The methodology features easily available catalysts, high catalytic
      efficiency and environmentally green procedures.

PMID- 22388775
TI  - The outcome of silicone intubation and tube removal in external
      dacryocystorhinostomy patients with distal canalicular obstruction.
AB  - PURPOSE: To evaluate the outcome of silicone intubation and tube removal in
      external dacryocystorhinostomy (DCR) patients with distal canalicular or common
      canalicular obstruction. METHOD: Seventy-five eyes of 69 patients with distal or
      common canalicular obstruction who had undergone external DCR and silicone tube
      insertion were included in the study. Silicone tube was left in place at least
      for 3 months. Presence of epiphora was questioned and patency was assessed by
      irrigation at each control after tube removal. RESULTS: Mean patient age was
      49.8+/-14.4 years (range 15-78) and mean follow-up after surgery was 13.2+/-4.2
      months (range 6-25). After tube removal, 16 eyes (21.3%) presented with epiphora
      and occluded canalicular systems. Two eyes (2.7%) presented with epiphora which
      started just after tube removal and had a patent canalicular system. Fifty-seven
      eyes (76%) were free of symptoms and had patent canalicular systems and 3 of
      these eyes (4%) had epiphora while the tube was in place. CONCLUSIONS: Silicone
      intubation is indicated in patients with distal or common canalicular
      obstruction. The majority of patients with canalicular problems are relieved of
      epiphora after silicone tube removal. However, the tube itself may transiently
      occlude the canalicular system and cause epiphora in some patients, and in some
      it can aid tear flow even in the presence of a patent system.

PMID- 22388776
TI  - Intracorneal hematoma after canaloplasty and clear cornea phacoemulsification:
      surgical management.
AB  - PURPOSE: This is a case report of intracorneal hematoma after canaloplasty and
      clear cornea phacoemulsification. METHODS: A 75-year-old woman presented with
      primary open angle glaucoma and visually significant cataract. Canaloplasty and
      clear corneal phacoemulsification were performed. Postoperatively she had an
      intracorneal hematoma, which was removed through a clear corneal tunnel. RESULTS:
      Preoperative best-corrected visual acuity (BCVA) was 20/40 in the right eye and
      mean intraocular pressure (IOP) was 20 mmHg. Uneventful canaloplasty, clear
      corneal phacoemulsification, and implantation of a posterior chamber intraocular
      lens were performed. One day after the operation, BCVA was 20/400 in the right
      eye. The IOP was 8 mmHg. Anterior segment examination revealed a nasally located
      intrastromal hematoma between corneal stroma and Descemet membrane. The
      intracorneal hematoma was removed through a clear corneal tunnel. Six months
      postoperatively, BCVA was 20/25 in the right eye. The IOP with one medication was
      17 mmHg. CONCLUSIONS: This operation was a minimally invasive technique to remove
      intrastromal hematocornea after viscocanaloplasty.

PMID- 22388777
TI  - Correlation between periventricular leukomalacia and retinopathy of prematurity.
AB  - PURPOSE: To investigate the correlation between periventricular leukomalacia
      (PVL) and retinopathy of prematurity (ROP), which are complications of perinatal
      and postnatal hypoxic-ischemic insults in premature infants. METHODS: In this
      retrospective case series study, from 1996 to 2008, after excluding cases with
      follow-up of less than 3 months, we reviewed medical charts of babies who had
      gestational age (GA) less than 30 weeks or birthweight (BW) less than 2000 g. A
      total of 195 patients were diagnosed with ROP and/or PVL and were enrolled in
      this analysis. We investigated the correlation between ROP and PVL with Pearson
      chi-square test and evaluated BW, GA, and Apgar scores at 1 minute and 5 minutes
      after birth as risk factors by independent t test. RESULTS: There were no
      significant differences in the prevalence of PVL between patients who received
      ROP treatment and those who did not receive ROP treatment. The BW was
      significantly lower in patients with PVL than in patients without PVL.
      Gestational age, BW, and Apgar scores significantly differed between patients who
      did and did not receive retinal treatment for ROP. CONCLUSIONS: Periventricular
      leukomalacia did not increase the severity of ROP or requirement of ROP
      treatment. Birthweight, GA, and Apgar scores were the principal factors that
      determined the necessity of ROP treatment.

PMID- 22388778
TI  - TSA-induced JMJD2B downregulation is associated with cyclin B1-dependent survivin
      degradation and apoptosis in LNCap cells.
AB  - Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor
      agents and have manifested the ability to induce apoptosis of cancer cells, and a
      significant number of genes have been identified as potential effectors
      responsible for HDAC inhibitor-induced apoptosis. However, the mechanistic
      actions of these HDAC inhibitors in this process remain largely undefined. We
      here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor
      trichostatin A (TSA) resulted in downregulation of the Jumonji domain-containing
      protein 2B (JMJD2B). We also found that the TSA-mediated decrease in survivin
      expression in LNCap cells was partly attributable to downregulation of JMJD2B
      expression. This effect was attributable to the promoted degradation of survivin
      protein through inhibition of Cyclin B1/Cdc2 complex-mediated survivin Thr34
      phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA-induced apoptosis
      by regulating the Cyclin B1-dependent survivin degradation to potentiate the
      apoptosis pathways.

PMID- 22388779
TI  - Development of a low-density polyethylene-containing passive sampler for
      measuring dissolved hydrophobic organic compounds in open waters.
AB  - A passive water sampler with low-density polyethylene (LDPE) as the sorbent phase
      was built and field-tested for sensing freely dissolved concentrations of
      hydrophobic organic compounds (HOCs) in fresh and coastal water. Based on the
      measured LDPE-water partition coefficients (K(pew)) of 12 polycyclic aromatic
      hydrocarbons (PAHs) and dichlorodiphenyltrichloroethane (DDT) and its seven
      metabolites, the detection limits with the passive sampler containing 10-g LDPE
      ranged from 0.04 to 56.9 pg/L in the equilibrium sampling mode. Furthermore, the
      utility of the passive sampler in measuring dissolved HOC concentrations in open
      waters was examined through a comparison with solid-phase extraction combined
      with liquid-liquid extraction (SPE-LLE) and poly(dimethyl)siloxane (PDMS) coated
      fiber samplers. The total concentrations of PAHs (3.8-16 ng/L) obtained by the
      passive sampler were lower than those (87.7-115.5 ng/L) obtained through SPE-LLE.
      This large difference was probably attributable to slower water exchange in and
      out of the passive sampler as time progressed because of blockage by algae in
      eutrophia reservoirs and high dissolved organic carbon contents resulting in
      higher-than-expected PAH concentrations by SPE-LLE. Furthermore, the
      concentrations and compositional profiles of DDXs (sum of p,p'-DDT, p,p'-DDD,
      p,p'-DDE, o,p'-DDT, o,p'-DDD, o,p'-DDE, and p,p'-DDMU) at site A obtained by the
      passive sampler agreed with the results obtained with the PDMS-coated fibers,
      suggesting that the passive sampler was able to reasonably quantify dissolved
      HOCs in seawater.

PMID- 22388780
TI  - A 'pivotal' new rule for microRNA-mRNA interactions.

PMID- 22388790
TI  - Cucurbit[8]uril-stabilized charge transfer complexes with diquat driven by pH: a
      SERS study.
AB  - In this work, we have studied the pH-dependence of the formation of DQCB[8]
      complexes by surface-enhanced Raman scattering (SERS) spectroscopy. The SERS
      spectra suggest that at acidic pH CB[8] can form a binary complex with the
      dication DQ(+2) while at higher pH ternary complexes with the radical cation
      dimer (DQ(+))(2) and the radical cation-dication dimer (DQ(+)DQ(+2)) are formed.
      The pH-enhanced diquat (DQ) dimerization inside the cucurbit[8]uril cavity has
      not been reported until now. In addition, this study provides very valuable
      information regarding the use of CB[8] functionalized silver nanoparticles as
      SERS substrate for sensing applications.

PMID- 22388791
TI  - Skeletal growth and IGF levels in rats after HT042 treatment.
AB  - HT042, a new herbal prescription consisting of Astragalus membranaceus, Phlomis
      umbrosa and Eleutherococcus senticosus, is used in traditional Korean medicine to
      stimulate growth in children. This study was conducted to investigate the effects
      of HT042 on skeletal growth, insulin-like growth factor-1 (IGF-1) and insulin
      like growth factor binding protein-3 (IGFBP-3) levels, and oestrogenic activity
      in female rats. Female Sprague-Dawley rats were divided into control, recombinant
      human growth hormone (rhGH; 20 ug/kg/day), and HT042 (100 mg/kg/day) groups and
      treated for 3 weeks. Axial skeletal growth, femur length, and growth plate length
      were measured every 3 weeks. The serum IGF-1 and IGFBP-3 levels were analysed.
      Moreover, the oestrogenic activity of the herbal extracts in the immature and
      ovariectomized rats was tested. The nose-anus, nose-tail, femur and growth-plate
      lengths were increased significantly in the HT042 group. Both IGF-1 and IGFBP-3
      were highly expressed in the hypertrophic zone of the growth plate. The serum IGF
      1 levels were increased. Moreover, HT042 had no uterotrophic effects in the rats.
      Consequently, HT042 promoted longitudinal bone growth by stimulating cell
      proliferation in the epiphyseal plate and inducing the expression of IGF-1
      without an oestrogenic response. HT042 may be helpful in stimulating growth in
      children with short stature.

PMID- 22388792
TI  - Thyroid hormone levels as a predictor of mortality in intensive care patients: A
      comparative prospective study.
AB  - BACKGROUND: Mortality rates of intensive care patients are quite high. The aim of
      this study was to determine the role, as well as to compare the value of several
      markers in predicting mortality in intensive care patients. Patient-wise, this is
      the largest study of its kind and the first that attempts to correlate the degree
      of thyroid hormone suppression with elevations in procalcitonin (PCT) levels.
      PATIENTS AND METHODS: In this study, a total of 417 patients were included in the
      final analysis, 235 of which were men (56%), and 182 were women (44%). Predictors
      of mortality that were investigated include age, APACHE II score, PCT, free
      triiodo-L-thyronine (fT3), free tetraiodothyronine/thyroxine (fT4) and thyroid
      stimulating hormone/thyrotropin (TSH). RESULTS: High APACHE II score and low PCT
      levels, as well as suppression of fT3, fT4 and TSH levels were all found to be
      associated with higher mortality in our intensive care patients (p < 0.001).
      Suppression of thyroid hormones was also found to be reciprocally correlated with
      high APACHE II scores and PCT levels (p < 0.05). CONCLUSION: Calculation of
      APACHE II score as well as measurement of PCT, fT3, fT4 and TSH levels may all be
      useful as predictors of mortality in intensive care patients.

PMID- 22388793
TI  - Muscle weakness, health status and frequency of exacerbations in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Multiple factors contribute to muscle weakness and reduced muscle
      mass in chronic obstructive pulmonary disease (COPD) and this impacts patients'
      quality of life. One factor implicated in this process is systemic inflammation,
      an accompaniment of acute exacerbations. Recurrent exacerbations are associated
      with lower health status. This study examines the relationship between muscle
      weaknesses, health status and exacerbation frequency in a cohort of patients with
      COPD. METHODS: This is an observational study of 188 (95 female) patients with
      COPD attending two hospital clinics in the northeast of England between 2004 and
      2007. We measured spirometry, body mass index, health status (St George's
      Respiratory Questionnaire) and grip strength and recorded Medical Research
      Council dyspnoea scores and the frequency of exacerbations in the previous year.
      RESULTS: Patients were aged 72.5+/-8.3 years (data expressed as mean+/-SD) with
      Medical Research Council score of 3.6+/-0.8, forced expiratory volume in one
      second (FEV(1)) of 49.2+/-21.5 per cent predicted and a total St George's
      Respiratory Questionnaire score of 72.2+/-15.5. Grip strength, expressed as per
      cent predicted, was 72.0+/-21.8 in men and 81.0+/-18.2 in women. Exacerbations
      ranged from zero to five in the previous year and there were associations of
      reduced grip strength with exacerbation frequency (chi(2)=9.634; p=0.0019) and
      lower health status (chi(2)=34.00; p<0.001). CONCLUSION: Our data clearly
      demonstrate that reduction in grip strength occurs more frequently and to a
      greater extent in patients with a history of frequent exacerbations and is
      associated with reduced health status.

PMID- 22388794
TI  - Disruption of exploratory and habituation behavior in mice with mutation of
      DISC1: an ethologically based analysis.
AB  - Disrupted-in-schizophrenia-1 (DISC1) is a gene that has been functionally linked
      with neurodevelopmental processes and structural plasticity in the brain.
      Clinical genetic investigations have implicated DISC1 as a genetic risk factor
      for schizophrenia and related psychoses. Studies using mutant mouse models of
      DISC1 gene function have demonstrated schizophrenia-related anatomical and
      behavioral endophenotypes. In the present study, ethologically based assessment
      of exploratory and habituation behavior in the open field was conducted in DISC1
      (L100P), wild-type (WT), heterozygous (HET), and homozygous (HOM) mutant mice of
      both sexes. Ethological assessment was conducted in an open-field environment to
      explore specific topographies of murine exploratory behavior across the extended
      course of interaction from initial exploration through subsequent habituation
      (the ethogram). During initial exploration, HET and HOM DISC1 mutants evidenced
      increased levels of locomotion and rearing to wall compared with WT. A HOM
      specific increase in total rearing and a HET-specific increase in sifting
      behavior and reduction in rearing seated were also observed. Over subsequent
      habituation, locomotion, sniffing, total rearing, rearing to wall, rearing free,
      and rearing seated were increased in HET and HOM mutants vs. WT. Overall,
      grooming was increased in HOM relative to other genotypes. HET mice displayed a
      selective decrease in habituation of sifting behavior. These data demonstrate
      impairment in both initial exploratory and habituation of exploration in a novel
      environment in mice with mutation of DISC1. This is discussed in the context of
      the functional role of the gene vis a vis a schizophrenia phenotype as well as
      the value of ethologically based approaches to behavioral phenotyping.

PMID- 22388795
TI  - Functional polymorphisms of folate metabolism and response to chemotherapy for
      colorectal cancer, a systematic review and meta-analysis.
AB  - OBJECTIVES: Many primary studies have considered the association of polymorphisms
      of folate metabolism and response to 5-fluorouracil (5-FU) and capecitabine in
      patients with colorectal cancer. The conclusions from these studies have been
      conflicting and few have considered large cohorts of patients. Therefore, we have
      completed a systematic review and meta-analyses to summarize some of the findings
      to date. We conducted searches for any studies that had addressed the prognostic
      value of genotype analysis of thymidylate synthetase (TYMS),
      Methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR).
      METHODS: We collected data on the study designs, and completed meta-analyses to
      pool congruent data about treatment effect. A narrative summary is presented for
      39 studies that describe three TYMS genotypes and two MTHFR genotypes associated
      with response to 5-FU-based chemotherapy. RESULTS: Data were synthesized from up
      to 2402 patients for the most commonly studied markers TYMS 5' UTR repeat
      polymorphism (rs45445694) and MTHFR 677 C>T (rs1801133). We found that the TYMS
      genotype associated with the lowest protein expression (2R/2R) was significantly
      associated with improved clinical benefit; the pooled risk ratio was relative
      risk=1.36 [1.11, 1.65]; P=0.003. Moreover, the same trend was observed for
      adverse effects; the pooled risk ratio was 2.04 [1.42, 2.95]; P=0.0001.
      CONCLUSION: There is a small but statistically significant association between
      treatment effect (both intended effects and adverse events) and a TYMS genotype
      associated with low protein expression; however, the effect size is small and
      therefore indicates limited clinical utility.

PMID- 22388796
TI  - The new CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with an
      increased risk of delayed graft function and worse renal function in cyclosporine
      treated kidney transplant patients.
AB  - OBJECTIVE: Cyclosporine A (CsA) is a substrate of cytochrome P450 3A4 (CYP3A4).
      Recently, a newly discovered intron 6 single-nucleotide polymorphism in CYP3A4
      (rs35599367 C>T), defining the CYP3A4*22 allele, has been linked to reduced
      hepatic expression and activity of CYP3A4. In the present study, the clinical
      impact of this single-nucleotide polymorphism was investigated in a cohort of
      patients receiving a CsA-based immunosuppressive regimen. MATERIALS AND METHODS:
      A total of 172 de-novo kidney transplant recipients, receiving CsA/mycophenolate
      mofetil as immunosuppressive therapy and participating in the Fixed-Dose
      Concentration Controlled study, were genotyped for the new CYP3A4*22 allele. CsA
      C(0) and/or C(2) levels were measured on days 3 and 10 and in months 1, 3, 6, and
      12 after transplantation. Plasma creatinine concentrations, delayed graft
      function (DGF), and biopsy-proven acute rejection were recorded. RESULTS: The
      CYP3A4*22 allele was significantly associated with a higher risk of DGF compared
      with the CYP3A4*1/*1 patients after adjustment for known risk factors [odds ratio
      (OR)=6.34, confidence interval (CI(95%): 1.38-29.3), P=0.015]. Mixed-model
      analysis demonstrated that the overall creatinine clearance was 20% lower in
      CYP3A4*22 allele carriers compared with CYP3A4*1/*1 patients [CI(95%) (-33.1 to 
      7.2%), P=0.002]. For ABCB1 3435C>T, T-variant carriers had a decreased risk of
      developing DGF compared with CC patients [CT: OR=0.30, CI(95%) (0.11-0.77),
      P=0.011; TT: OR=0.18, CI(95%) (0.05-0.67), P=0.011]. CONCLUSION: CYP3A4*22
      constitutes a risk factor for DGF and worse creatinine clearance in patients
      receiving CsA-based immunosuppressive therapy. Therefore, pretransplant
      genotyping for the CYP3A4*22 allele might help clinicians to identify patients at
      risk of DGF and poor renal function when treated with CsA.

PMID- 22388797
TI  - Imatinib therapy of chronic myeloid leukemia restores the expression levels of
      key genes for DNA damage and cell-cycle progression.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a malignant clonal disorder of the
      hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. It
      is well known that CML cells are genetically unstable. However, the mechanisms by
      which these cells acquire genetic alterations are poorly understood. Imatinib
      mesylate is the standard therapy for newly diagnosed CML patients. Imatinib
      mesylate targets the oncogenic kinase activity of BCR-ABL. OBJECTIVE: To study
      the gene expression profile of bone marrow hematopoietic cells in the same
      patients with CML before and 1 month after imatinib therapy. METHODS: Samples
      from patients with CML were analyzed using Affymetrix GeneChip Expression Arrays.
      RESULTS: A total of 594 differentially expressed genes, most of which (393 genes)
      were downregulated, as a result of imatinib therapy were observed. CONCLUSION:
      The blockade of oncoprotein Bcr-Abl by imatinib could cause a decrease in the
      expression of key DNA repair genes and substantially modify the expression
      profile of the bone marrow cells in the first days of therapy.

PMID- 22388799
TI  - The rebirth of kinship: evolutionary and quantitative approaches in the
      revitalization of a dying field.
AB  - Kinship was one of the key areas of research interest among anthropologists in
      the nineteenth century, one of the most hotly debated areas of theory in the
      early and mid-twentieth century, and yet an area of waning interest by the end of
      the twentieth century. Since then, the study of kinship has experienced a
      revitalization, with concomitant disputes over how best to proceed. This special
      issue brings together recent studies of kinship by scientific anthropologists
      employing evolutionary theory and quantitative methods. We argue that the melding
      of the evolutionary theoretical perspective with quantitative and ethnographic
      methodologies has strengthened and reinvigorated the study of kinship by
      synthesizing and extending existing research via rigorous analyses of evidence.

PMID- 22388798
TI  - Gene panels to help identify subgroups at high and low risk of coronary heart
      disease among those randomized to antihypertensive treatment:  the GenHAT study.
AB  - OBJECTIVE: To identify panels of genetic variants that predict treatment-related
      coronary heart disease (CHD) outcomes in hypertensive patients on one of four
      different classes of initial antihypertensive treatment. The goal was to identify
      subgroups of individuals on the basis of their genetic profile who benefit most
      from a particular treatment. METHODS: Candidate genetic variants (n=78) were
      genotyped in 39 114 participants from Genetics of Hypertension Associated
      Treatment study, ancillary to Antihypertensive and Lipid Lowering Treatment to
      Prevent Heart Attack Trial. Antihypertensive and Lipid Lowering Treatment to
      Prevent Heart Attack Trial randomized hypertensive participants (>=55 years) to
      one of four treatments (amlodipine, chlorthalidone, doxazosin, lisinopril). The
      primary outcome was fatal CHD or nonfatal myocardial infarction (mean follow
      up=4.9 years). A pharmacogenetic panel was derived within each of the four
      treatment groups. Receiver-operating characteristic (ROC) curves estimated the
      discrimination rate between those with and without a CHD event, on the basis of
      the addition of the genetic panel risk score. RESULTS: For each treatment group,
      we identified a panel of genetic variants that collectively improved the
      prediction of CHD to a small but statistically significant extent. Chlorthalidone
      (A): NOS3 rs3918226; SELE rs5361; ICAM1 rs1799969; AGT rs5051; GNAS rs7121; ROC
      comparison, P=0.004; Amlodipine (B): MMP1 rs1799750; Factor5 (F5) rs6025; NPPA
      rs5065; PDE4D rs6450512; MMP9 rs2274756; ROC comparison, P=0.006; Lisinopril (C):
      AGT rs5051; PON1 rs705379; MMP12 rs652438; F12 rs1801020; GP1BA rs6065; PDE4D
      rs27653; ROC comparison, P=0.01; Doxazosin (D): F2 rs1799963; PAI1 rs1799768;
      MMP7 rs11568818; AGT rs5051; ACE rs4343; MMP2 rs243865; ROC comparison, P=0.007.
      Each panel was tested for a pharmacogenetic effect; panels A, B, and D showed
      such evidence (P=0.009, 0.006, and 0.001, respectively) and panel C did not
      (P=0.09). CONCLUSION: Because each panel was associated with CHD in a specific
      treatment group but not the others, this research provides evidence that it may
      be possible to use gene panel scores as a tool to better assess antihypertensive
      treatment choices to reduce CHD risk in hypertensive individuals.

PMID- 22388800
TI  - Postmarital residence and bilateral kin associations among hunter-gatherers: Pume
      foragers living in the best of both worlds.
AB  - Dispersal of individuals from their natal communities at sexual maturity is an
      important determinant of kin association. In this paper we compare postmarital
      residence patterns among Pume foragers of Venezuela to investigate the prevalence
      of sex-biased vs. bilateral residence. This study complements cross-cultural
      overviews by examining postmarital kin association in relation to individual,
      longitudinal data on residence within a forager society. Based on cultural norms,
      the Pume have been characterized as matrilocal. Analysis of Pume marriages over a
      25-year period finds a predominant pattern of natalocal residence. We emphasize
      that natalocality, bilocality, and multilocality accomplish similar ends in
      maximizing bilateral kin affiliations in contrast to sex-biased residential
      patterns. Bilateral kin association may be especially important in foraging
      economies where subsistence activities change throughout the year and large kin
      networks permit greater potential flexibility in residential mobility.

PMID- 22388801
TI  - Evolutionary contributions to solving the "matrilineal puzzle": a test of Holden,
      Sear, and Mace's model.
AB  - Matriliny has long been debated by anthropologists positing either its primitive
      or its puzzling nature. More recently, evolutionary anthropologists have
      attempted to recast matriliny as an adaptive solution to modern social and
      ecological environments, tying together much of what was known to be associated
      with matriliny. This paper briefly reviews the major anthropological currents in
      studies of matriliny and discusses the contribution of evolutionary anthropology
      to this body of literature. It discusses the utility of an evolutionary framework
      in the context of the first independent test of Holden et al.'s 2003 model of
      matriliny as daughter-biased investment. It finds that historical daughter-biased
      transmission of land among the Mosuo is consistent with the model, whereas
      current income transmission is not. In both cases, resources had equivalent
      impacts on male and female reproduction, a result which predicts daughter-biased
      resource transmission given any nonzero level of paternity uncertainty. However,
      whereas land was transmitted traditionally to daughters, income today is invested
      in both sexes. Possible reasons for this discrepancy are discussed.

PMID- 22388802
TI  - Genetic and cultural kinship among the Lamaleran whale hunters.
AB  - The human ability to form large, coordinated groups is among our most impressive
      social adaptations. Larger groups facilitate synergistic economies of scale for
      cooperative breeding, such economic tasks as group hunting, and success in
      conflict with other groups. In many organisms, genetic relationships provide the
      structure for sociality to evolve via the process of kin selection, and this is
      the case, to a certain extent, for humans. But assortment by genetic affiliation
      is not the only mechanism that can bring people together. Affinity based on
      symbolically mediated and socially constructed identity, or cultural kinship,
      structures much of human ultrasociality. This paper examines how genetic kinship
      and two kinds of cultural kinship--affinal kinship and descent--structure the
      network of cooperating whale hunters in the village of Lamalera, Indonesia.
      Social network analyses show that each mechanism of assortment produces
      characteristic networks of different sizes, each more or less conducive to the
      task of hunting whales. Assortment via close genetic kin relationships (r = 0.5)
      produces a smaller, denser network. Assortment via less-close kin relations (r =
      0.125) produces a larger but less dense network. Affinal networks are small and
      diffuse; lineage networks are larger, discrete, and very dense. The roles that
      genetic and cultural kinship play for structuring human sociality is discussed in
      the context of these results.

PMID- 22388803
TI  - The place of proximity: social support in mother-adult daughter relationships.
AB  - The mother-adult daughter relationship has been highlighted in both the social
      sciences and the public health literature as an important facet of social support
      networks, particularly as they pertain to maternal and child health. Evolutionary
      anthropologists also have shown positive associations between support from
      maternal grandmothers and various outcomes related to reproductive success;
      however, many of these studies rely on proximity as a surrogate measure of
      support. Here I present data from the Puerto Rican Maternal and Infant Health
      Survey (PRMIHS) comparing geographic proximity of mother and daughter with a self
      reported measure of mother-to-daughter support. These two measures were used to
      predict infant health outcomes as well as various measures of instrumental and
      emotional aid provided during pregnancy and after birth. Primary support was
      shown to have a positive effect across the analyses, whereas geographic proximity
      was associated with an increased risk of infant mortality and low birth weight as
      well as reduced odds of receiving support. This paradox was then examined using a
      combination variable that teased out the interactions of maternal support and
      proximity. Women who were geographically close to their mothers but who did not
      consider them a primary source of support had increased odds of infant death and
      low birth weight, and were less likely to receive either tangible or intangible
      forms of aid, while women whose mothers were both close and primary showed
      uniformly positive outcomes. These results place the role of propinquity within
      the larger context of social support and highlight the need for more detailed
      studies of social support within evolutionary anthropology.

PMID- 22388804
TI  - Dynamics of postmarital residence among the Hadza: a kin investment model.
AB  - When we have asked Hadza whether married couples should live with the family of
      the wife (uxorilocally) or the family of the husband (virilocally), we are often
      told that young couples should spend the first years of a marriage living with
      the wife's family, and then later, after a few children have been born, the
      couple has more freedom--they can continue to reside with the wife's kin, or else
      they could join the husband's kin, or perhaps live in a camp where there are no
      close kin. In this paper, we address why shifts in kin coresidence patterns may
      arise in the later years of a marriage, after the birth of children. To do so, we
      model the inclusive fitness costs that wives might experience from leaving their
      own kin and joining their husband's kin as a function of the number of children
      in their nuclear family. Our model suggests that such shifts should become less
      costly to wives as their families grow. This simple model may help explain some
      of the dynamics of postmarital residence among the Hadza and offer insight into
      the dynamics of multilocal residence, the most prevalent form of postmarital
      residence among foragers.

PMID- 22388805
TI  - Urbanization and daughter-biased parental investment in Fiji.
AB  - Parental investment decisions guide parental actions regarding children's
      productive work and are shaped by ecological context. Urban ecology enhances long
      term payoffs to investment in human capital, increasing opportunity costs for
      work performed by children, and decreased workload should result. Using an
      embodied capital framework, self-reported data on urban and rural Indo-Fijian
      children's work activities are compared. Results show higher workloads for older
      children, rural children, and girls. High scholastic achievement is associated
      with lower workloads for girls, but not boys. This pattern is interpreted as
      daughter-biased investment in the context of urbanization.

PMID- 22388806
TI  - Kin preference and partner choice: patrilineal descent and biological kinship in
      Lamaleran cooperative relationships.
AB  - This paper presents a comparison of social kinship (patrilineage) and biological
      kinship (genetic relatedness) in predicting cooperative relationships in two
      different economic contexts in the fishing and whaling village of Lamalera,
      Indonesia. A previous analysis (Alvard, Human Nature 14:129-163, 2003) of boat
      crew affiliation data collected in the village in 1999 found that social kinship
      (patrilineage) was a better predictor of crew affiliation than was genetic
      kinship. A replication of this analysis using similar data collected in 2006
      finds the same pattern: lineage is a better predictor than genetic kinship of
      crew affiliation, and the two together explain little additional variance over
      that explained by lineage alone. However, an analogous test on food-sharing
      relationships finds the opposite pattern: biological kinship is a better
      predictor of food-sharing relationships than is social kinship. The difference
      between these two cooperative contexts is interpreted in terms of kin preferences
      that shape partner choice, and the relative autonomy with which individuals can
      seek to satisfy those preferences. Drawing on stable matching theory, it is
      suggested that unilineal descent may serve as a stable compromise among multiple
      individuals' incongruent partner preferences, with patriliny favored over
      matriliny in the crew-formation context because it leads to higher mean degrees
      of relatedness among male cooperators. In the context of food-sharing, kin
      preferences can be pursued relatively autonomously, without the necessity of
      coordinating preferences with those of other households through the institution
      of lineage.

PMID- 22388807
TI  - The matrilocal tribe: an organization of demic expansion.
AB  - This article integrates (1) research in the historical dynamics of state
      societies relating group solidarity and group expansion to cultural frontiers,
      (2) comparative research in anthropology relating matrilocality to a particular
      variety of internal politics and a particular form of warfare, and (3)
      interdisciplinary reconstructions of large-scale "demic expansions" and
      associated kinship systems in prehistory. The argument is that "metaethnic
      frontiers," where very different cultures clash, are centers for the formation of
      larger, more enduring, and more militarily effective groups. In small-scale non
      state societies, the major path toward the formation of such groups is the
      establishment of cross-cutting ties among men. This often involves the adoption
      of matrilocal norms. The current distribution of matrilocality and matrilineality
      around the world may be partly a residue of major demic expansions in prehistory
      involving matrilocal tribes. This hypothesis is evaluated with a range of
      evidence, including information regarding the spread of two language families,
      Bantu and Austronesian.

PMID- 22388808
TI  - Alternatives to the grandmother hypothesis: a meta-analysis of the association
      between grandparental and grandchild survival in patrilineal populations.
AB  - We conducted a meta-analysis of 17 studies that tested for an association between
      grandparental survival and grandchild survival in patrilineal populations. Using
      two different methodologies, we found that the survival of the maternal
      grandmother and grandfather, but not the paternal grandmother and grandfather,
      was associated with decreased grandoffspring mortality. These results are
      consistent with the findings of psychological studies in developed countries
      (Coall and Hertwig Behavioral and Brain Sciences 33:1-59, 2010). When tested
      against the predictions of five hypotheses (confidence of paternity;
      grandmothering, kin proximity, grandparental senescence, and local resource
      competition), our meta-analysis results are most in line with the local resource
      competition hypothesis. In patrilineal and predominantly patrilocal societies,
      the grandparents who are most likely to live with the grandchildren have a less
      beneficial association than those who do not. We consider the extent to which
      these results may be influenced by the methodological limitations of the source
      studies, including the use of retrospective designs and inadequate controls for
      confounding variables such as wealth.

PMID- 22388809
TI  - Genome-wide expression profiling of the response to linezolid in Mycobacterium
      tuberculosis.
AB  - Tuberculosis (TB) is still one of the most common causes of death in the world.
      The emergence of multidrug-resistant and extensively drug-resistant (XDR-TB)
      Mycobacterium tuberculosis (M. tuberculosis) strains has increased the importance
      of searching for alternative targets to develop new antimycobacterial drugs.
      Linezolid, the first of oxazolidinones, is active in vitro against M.
      tuberculosis, but the response mechanisms of M. tuberculosis to linezolid are
      still poorly understood. To reveal the possible mechanism of action of linezolid
      against M. tuberculosis, commercial oligonucleotide microarrays were used to
      analyze the genome-wide transcriptional changes triggered by treatment with
      subinhibitory concentrations of linezolid. Quantitative real-time RT-PCR was
      performed for selected genes to verify the microarray results. A total of 729
      genes were found to be differentially regulated by linezolid. Among these, 318
      genes were upregulated, and 411 genes were downregulated. A number of important
      genes were significantly regulated that are involved in various pathways, such as
      protein synthesis, sulfite metabolism, and genes involved in the cell envelope
      and virulence. This genome-wide transcriptomics approach produced the first
      insights into the response of M. tuberculosis to a linezolid challenge.

PMID- 22388810
TI  - Neuroscience: how brains learn to control machines.

PMID- 22388811
TI  - Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain.
AB  - All attempts at treating strokes by pharmacologically reducing the human brain's
      vulnerability to ischaemia have failed, leaving stroke as a leading cause of
      death, disability and massive socioeconomic loss worldwide. Over decades,
      research has failed to translate over 1,000 experimental treatments from
      discovery in cells and rodents to use in humans, a scientific crisis that gave
      rise to the prevailing belief that pharmacological neuroprotection is not
      feasible or practicable in higher-order brains. To provide a strategy for
      advancing stroke therapy, we used higher-order gyrencephalic non-human primates,
      which bear genetic, anatomical and behavioural similarities to humans and tested
      neuroprotection by PSD-95 inhibitors--promising compounds that uncouple
      postsynaptic density protein PSD-95 from neurotoxic signalling pathways. Here we
      show that stroke damage can be prevented in non-human primates in which a PSD-95
      inhibitor is administered after stroke onset in clinically relevant situations.
      This treatment reduced infarct volumes as gauged by magnetic resonance imaging
      and histology, preserved the capacity of ischaemic cells to maintain gene
      transcription in genome-wide screens of ischaemic brain tissue, and significantly
      preserved neurological function in neurobehavioural assays. The degree of tissue
      neuroprotection by magnetic resonance imaging corresponded strongly to the
      preservation of neurological function, supporting the intuitive but unproven
      dictum that integrity of brain tissue can reflect functional outcome. Our
      findings establish that tissue neuroprotection and improved functional outcome
      after stroke is unequivocally achievable in gyrencephalic non-human primates
      treated with PSD-95 inhibitors. Efforts must ensue to translate these findings to
      humans.

PMID- 22388812
TI  - Diverse transitional giant fleas from the Mesozoic era of China.
AB  - Fleas are one of the major lineages of ectoparasitic insects and are now highly
      specialized for feeding on the blood of birds or mammals. This has isolated them
      among holometabolan insect orders, although they derive from the Antliophora
      (scorpionflies and true flies). Like most ectoparasitic lineages, their fossil
      record is meagre and confined to Cenozoic-era representatives of modern families,
      so that we lack evidence of the origins of fleas in the Mesozoic era. The origins
      of the first recognized Cretaceous stem-group flea, Tarwinia, remains highly
      controversial. Here we report fossils of the oldest definitive fleas--giant forms
      from the Middle Jurassic and Early Cretaceous periods of China. They exhibit many
      defining features of fleas but retain primitive traits such as non-jumping
      hindlegs. More importantly, all have stout and elongate sucking siphons for
      piercing the hides of their hosts, implying that these fleas may be rooted among
      the pollinating 'long siphonate' scorpionflies of the Mesozoic. Their special
      morphology suggests that their earliest hosts were hairy or feathered
      'reptilians', and that they radiated to mammalian and bird hosts later in the
      Cenozoic.

PMID- 22388813
TI  - Chromatin-modifying enzymes as modulators of reprogramming.
AB  - Generation of induced pluripotent stem cells (iPSCs) by somatic cell
      reprogramming involves global epigenetic remodelling. Whereas several proteins
      are known to regulate chromatin marks associated with the distinct epigenetic
      states of cells before and after reprogramming, the role of specific chromatin
      modifying enzymes in reprogramming remains to be determined. To address how
      chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs
      (shRNAs) to target genes in DNA and histone methylation pathways, and identified
      positive and negative modulators of iPSC generation. Whereas inhibition of the
      core components of the polycomb repressive complex 1 and 2, including the histone
      3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression
      of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the
      H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated
      reprogramming, significantly increased the yield of iPSC colonies, and
      substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in
      the reprogramming process is associated with a marked increase in two alternative
      factors, NANOG and LIN28, which play essential functional roles in the
      enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution
      revealed that fibroblast-specific genes associated with the epithelial to
      mesenchymal transition lose H3K79me2 in the initial phases of reprogramming.
      DOT1L inhibition facilitates the loss of this mark from genes that are fated to
      be repressed in the pluripotent state. These findings implicate specific
      chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and
      demonstrate how modulation of chromatin-modifying enzymes can be exploited to
      more efficiently generate iPSCs with fewer exogenous transcription factors.

PMID- 22388815
TI  - Coevolution in multidimensional trait space favours escape from parasites and
      pathogens.
AB  - Almost all species are subject to continuous attack by parasites and pathogens.
      Because parasites and pathogens tend to have shorter generation times and often
      experience stronger selection due to interaction than their victims do, it is
      frequently argued that they should evolve more rapidly and thus maintain an
      advantage in the evolutionary race between defence and counter-defence. This
      prediction generates an apparent paradox: how do victim species survive and even
      thrive in the face of a continuous onslaught of more rapidly evolving enemies?
      One potential explanation is that defence is physiologically, mechanically or
      behaviourally easier than attack, so that evolution is less constrained for
      victims than for parasites or pathogens. Another possible explanation is that
      parasites and pathogens have enemies themselves and that victim species persist
      because parasites and pathogens are regulated from the top down and thus
      generally have only modest demographic impacts on victim populations. Here we
      explore a third possibility: that victim species are not as evolutionarily
      impotent as conventional wisdom holds, but instead have unique evolutionary
      advantages that help to level the playing field. We use quantitative genetic
      analysis and individual-based simulations to show that victims can achieve such
      an advantage when coevolution involves multiple traits in both the host and the
      parasite.

PMID- 22388814
TI  - An epigenetic blockade of cognitive functions in the neurodegenerating brain.
AB  - Cognitive decline is a debilitating feature of most neurodegenerative diseases of
      the central nervous system, including Alzheimer's disease. The causes leading to
      such impairment are only poorly understood and effective treatments are slow to
      emerge. Here we show that cognitive capacities in the neurodegenerating brain are
      constrained by an epigenetic blockade of gene transcription that is potentially
      reversible. This blockade is mediated by histone deacetylase 2, which is
      increased by Alzheimer's-disease-related neurotoxic insults in vitro, in two
      mouse models of neurodegeneration and in patients with Alzheimer's disease.
      Histone deacetylase 2 associates with and reduces the histone acetylation of
      genes important for learning and memory, which show a concomitant decrease in
      expression. Importantly, reversing the build-up of histone deacetylase 2 by short
      hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates
      structural and synaptic plasticity, and abolishes neurodegeneration-associated
      memory impairments. These findings advocate for the development of selective
      inhibitors of histone deacetylase 2 and suggest that cognitive capacities
      following neurodegeneration are not entirely lost, but merely impaired by this
      epigenetic blockade.

PMID- 22388816
TI  - Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis.
AB  - Polycyclic polyether natural products have fascinated chemists and biologists
      alike owing to their useful biological activity, highly complex structure and
      intriguing biosynthetic mechanisms. Following the original proposal for the
      polyepoxide origin of lasalocid and isolasalocid and the experimental
      determination of the origins of the oxygen and carbon atoms of both lasalocid and
      monensin, a unified stereochemical model for the biosynthesis of polyether
      ionophore antibiotics was proposed. The model was based on a cascade of
      nucleophilic ring closures of postulated polyepoxide substrates generated by
      stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly
      thereafter, a related model was proposed for the biogenesis of marine ladder
      toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet
      epoxide-ring-opening reactions. Recently, we identified Lsd19 from the
      Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for
      the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A.
      Here we report the X-ray crystal structure of Lsd19 in complex with its substrate
      and product analogue to provide the first atomic structure-to our knowledge-of a
      natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether
      formation. On the basis of our structural and computational studies, we propose a
      general mechanism for the enzymatic catalysis of polyether natural product
      biosynthesis.

PMID- 22388817
TI  - Uncovering the Neoproterozoic carbon cycle.
AB  - Interpretations of major climatic and biological events in Earth history are, in
      large part, derived from the stable carbon isotope records of carbonate rocks and
      sedimentary organic matter. Neoproterozoic carbonate records contain unusual and
      large negative isotopic anomalies within long periods (10-100 million years)
      characterized by delta(13)C in carbonate (delta(13)C(carb)) enriched to more than
      +5 per mil. Classically, delta(13)C(carb) is interpreted as a metric of the
      relative fraction of carbon buried as organic matter in marine sediments, which
      can be linked to oxygen accumulation through the stoichiometry of primary
      production. If a change in the isotopic composition of marine dissolved inorganic
      carbon is responsible for these excursions, it is expected that records of
      delta(13)C(carb) and delta(13)C in organic carbon (delta(13)C(org)) will covary,
      offset by the fractionation imparted by primary production. The documentation of
      several Neoproterozoic delta(13)C(carb) excursions that are decoupled from
      delta(13)C(org), however, indicates that other mechanisms may account for these
      excursions. Here we present delta(13)C data from Mongolia, northwest Canada and
      Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon
      isotope anomalies, and use these data in a new quantitative mixing model to
      examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate
      and organic carbon isotope data from Mongolia and Canada are tightly coupled
      through multiple delta(13)C(carb) excursions, quantitatively ruling out
      previously suggested alternative explanations, such as diagenesis or the presence
      and terminal oxidation of a large marine dissolved organic carbon reservoir. Our
      data from Namibia, which do not record isotopic covariance, can be explained by
      simple mixing with a detrital flux of organic matter. We thus interpret
      delta(13)C(carb) anomalies as recording a primary perturbation to the surface
      carbon cycle. This interpretation requires the revisiting of models linking
      drastic isotope excursions to deep ocean oxygenation and the opening of
      environments capable of supporting animals.

PMID- 22388818
TI  - Corticostriatal plasticity is necessary for learning intentional neuroprosthetic
      skills.
AB  - The ability to learn new skills and perfect them with practice applies not only
      to physical skills but also to abstract skills, like motor planning or
      neuroprosthetic actions. Although plasticity in corticostriatal circuits has been
      implicated in learning physical skills, it remains unclear if similar circuits or
      processes are required for abstract skill learning. Here we use a novel
      behavioural task in rodents to investigate the role of corticostriatal plasticity
      in abstract skill learning. Rodents learned to control the pitch of an auditory
      cursor to reach one of two targets by modulating activity in primary motor cortex
      irrespective of physical movement. Degradation of the relation between action and
      outcome, as well as sensory-specific devaluation and omission tests, demonstrate
      that these learned neuroprosthetic actions are intentional and goal-directed,
      rather than habitual. Striatal neurons change their activity with learning, with
      more neurons modulating their activity in relation to target-reaching as learning
      progresses. Concomitantly, strong relations between the activity of neurons in
      motor cortex and the striatum emerge. Specific deletion of striatal NMDA
      receptors impairs the development of this corticostriatal plasticity, and
      disrupts the ability to learn neuroprosthetic skills. These results suggest that
      corticostriatal plasticity is necessary for abstract skill learning, and that
      neuroprosthetic movements capitalize on the neural circuitry involved in natural
      motor learning.

PMID- 22388819
TI  - Skin infection generates non-migratory memory CD8+ T(RM) cells providing global
      skin immunity.
AB  - Protective T-cell memory has long been thought to reside in blood and lymph
      nodes, but recently the concept of immune memory in peripheral tissues mediated
      by resident memory T (T(RM)) cells has been proposed. Here we show in mice that
      localized vaccinia virus (VACV) skin infection generates long-lived non
      recirculating CD8(+) skin T(RM) cells that reside within the entire skin. These
      skin T(RM) cells are potent effector cells, and are superior to circulating
      central memory T (T(CM)) cells at providing rapid long-term protection against
      cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin
      after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of
      CD4(+) T cells and interferon-gamma, but requires the expression of E- and P
      selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that
      circulating CD8(+) T(CM) and CD8(+) skin T(RM) cells are both generated after
      skin infection; however, CD8(+) T(CM) cells recirculate between blood and lymph
      nodes whereas T(RM) cells remain in the skin. Cutaneous CD8(+) T(RM) cells
      produce effector cytokines and persist for at least 6 months after infection.
      Mice with CD8(+) skin T(RM) cells rapidly cleared a subsequent re-infection with
      VACV whereas mice with circulating T(CM) but no skin T(RM) cells showed greatly
      impaired viral clearance, indicating that T(RM) cells provide superior
      protection. Finally, we show that T(RM) cells generated as a result of localized
      VACV skin infection reside not only in the site of infection, but also populate
      the entire skin surface and remain present for many months. Repeated re
      infections lead to progressive accumulation of highly protective T(RM) cells in
      non-involved skin. These findings have important implications for our
      understanding of protective immune memory at epithelial interfaces with the
      environment, and suggest novel strategies for vaccines that protect against
      tissue tropic organisms.

PMID- 22388820
TI  - Structural basis of ultraviolet-B perception by UVR8.
AB  - The Arabidopsis thaliana protein UVR8 is a photoreceptor for ultraviolet-B. Upon
      ultraviolet-B irradiation, UVR8 undergoes an immediate switch from homodimer to
      monomer, which triggers a signalling pathway for ultraviolet protection. The
      mechanism by which UVR8 senses ultraviolet-B remains largely unknown. Here we
      report the crystal structure of UVR8 at 1.8 A resolution, revealing a symmetric
      homodimer of seven-bladed beta-propeller that is devoid of any external cofactor
      as the chromophore. Arginine residues that stabilize the homodimeric interface,
      principally Arg 286 and Arg 338, make elaborate intramolecular cation-pi
      interactions with surrounding tryptophan amino acids. Two of these tryptophans,
      Trp 285 and Trp 233, collectively serve as the ultraviolet-B chromophore. Our
      structural and biochemical analyses identify the molecular mechanism for UVR8
      mediated ultraviolet-B perception, in which ultraviolet-B radiation results in
      destabilization of the intramolecular cation-pi interactions, causing disruption
      of the critical intermolecular hydrogen bonds mediated by Arg 286 and Arg 338 and
      subsequent dissociation of the UVR8 homodimer.

PMID- 22388822
TI  - [Dyslipidemia: news in diagnosis and drug therapy].
AB  - Plasma lipid levels are to a large extent determined by genetic factors. In its
      more extreme forms this is manifested as familial hyperlipidemias, which are an
      important cause of premature coronary heart disease. It has been demonstrated
      that rigorous treatment of familial forms reduces the burden of ischemic heart
      disease. Statins are among the most studied drugs in cardiovascular prevention; a
      number of large-scale clinical trials have demonstrated that statins
      substantially reduce cardiovascular morbidity and mortality in both primary and
      secondary prevention. The currently available evidence suggests that the clinical
      benefit is largely independent of the type of statin, but depends on the extent
      of LDL-C lowering. When the most potent statins are insufficient, LDL-C apheresis
      should be used.

PMID- 22388823
TI  - [LDL apheresis: an update and overview. LDL apheresis in Sardinia, Italy
      (SMILDLa)].
AB  - LDL apheresis (LDLa) is an invasive therapeutic tool to control qualitative and
      quantitative disorders of lipid metabolism. It is aimed at achieving a metabolic
      balance in association with lipid-lowering drugs in patients with severe,
      genetically determined or acquired dyslipidemia who do not reach clinically
      adequate LDL-cholesterol (LDL-C) levels (<70 mg/dL) despite appropriate lipid
      lowering drug treatment. A poorly known dyslipidemia is constituted by elevation
      of lipoprotein (a) [Lp(a)], which appears to be genetically determined and not
      influenced by diet or lipid-lowering medication. An Lp(a) level exceeding 30
      mg/dL is an independent risk factor for premature cardiovascular disease and
      cerebrovascular disease. Numerous data support the notion that cardiovascular
      risk reduction is related to the degree of reduction of LDL-C, and the
      progression of atherosclerosis can be delayed or reversed by intensive and
      continuous cholesterol-lowering treatment. After the introduction of HMG-CoA
      reductase inhibitors (statins), the clinical benefit of cholesterol-lowering
      treatment has received significant confirmation. However, this treatment has
      shown poor results in the most severe, genetically determined forms. LDLa is an
      intensive extracorporeal cholesterol-lowering treatment approach with well
      documented efficacy and safety. It has also shown effects not directly correlated
      with its lipid-lowering activity, such as antioxidant effects on oxidized LDL and
      antiinflammatory effects on the cytokine network, the endothelium and the
      coagulation system. Finally, data acquired by the Italian Multicenter Study on
      LDLa Working Group were highlighted and the new evidence in the literature
      discussed.

PMID- 22388824
TI  - [LDL-apheresis in Sardinia, Italy].
AB  - A steady increase in mean serum cholesterol levels has been observed in the
      Sardinian population over the past three decades, probably related to
      modifications in the diet such as the introduction of fast food; however, the
      mean serum values are still lowest compared with the other Italian regions. These
      data clearly contrast with the presence in our area of five LDL-apheresis centers
      where, in 20 years of activity, over 16,000 treatments were performed in 60
      patients, accounting for 30% of LDL-apheresis-treated patients in Italy. The
      contrast is even more surprising when one considers that Sardinia has a
      population of only 1.6 million, i.e., 2.8% of the Italian population. A recessive
      form of familial hypercholesterolemia, called ARH, was recently discovered and
      studied in the Sardinian population. It has a prevalence of about 1:38,000-
      40,000 for homozygous and double heterozygous subjects, who show clinical
      features similar to those of classical homozygous familial hypercholesterolemia,
      a disease characterized by autosomal dominant transmission.

PMID- 22388825
TI  - [Indications for apheresis in kidney transplant recipients: apheresis in the
      hyperimmune patient].
AB  - Patients who are sensitized through pregnancy, previous blood transfusions, or
      organ transplantation produce donor-specific anti-HLA antibodies (DSA) that can
      result in an important obstacle in kidney transplantation. Sensitized patients
      wait longer on the cadaver donor transplant list, may not receive a transplant,
      and may have greater morbidity and mortality. Sensitized patients may have living
      donor candidates but transplantation cannot be performed because of cross-match
      positivity. Kidney transplant recipients with DSA are at higher risk of
      developing early acute antibody-mediated rejection (AMR) despite negative
      complement-dependent cytotoxicity (CDC) T-cell cross-match, and thus require
      desensitization. Desensitization protocols using the combination of apheresis
      (PE) or immunoadsorption to remove DSA and/or intravenous Ig (Iv-Ig) and
      rituximab to downregulate antibody-mediated immune responses have made kidney
      transplantation feasible by abrogating CDC T-cell cross-match positivity. All
      sensitized patients should be studied for DSA by sensitive methods and followed
      over time. The presence of DSA should be documented, and also the strength or
      titers of the alloantibodies should be determined to decide on the type of
      desensitization protocol. High-dosage Iv-Ig alone does not prevent AMR in
      patients with strong DSA, and the addition of peritransplantation PE as
      unselective plasma exchange, semiselective double filtration, or selective
      immunoadsorption significantly decreases the incidence of AMR. The effect of
      addition of monoclonal antibodies such as rituximab to desensitization protocols
      or of PE to patients with strong anti-HLA-II DSA on allograft outcomes requires
      further prospective studies.

PMID- 22388826
TI  - [Apheresis in ABO-incompatible kidney transplant].
AB  - Living donor kidney transplantation is the preferred therapeutic option for
      patients with end stage renal disease. Unfortunately, about 20-30% of potential
      living kidney donors are rejected because of incompatible immunological barriers
      such as ABO incompatibility. The newest desensitization protocols based on
      therapeutic apheresis and perioperative immunosuppressive drugs have allowed to
      overcome antibody barriers. The aim of these protocols is to wash out and
      suppress as many anti-A or anti-B antibodies as possible and to prevent rebound
      phenomena after transplantation. Standard plasmapheresis, double-filtration
      plasmapheresis, and selective immunoadsorption are among the most common
      apheresis modalities applied in ABO-incompatible transplantation. Selective
      immunoadsorption appears to be much safer and to have markedly increased efficacy
      compared with plasmapheresis, as it eliminates almost exclusively blood-group
      antibodies, thus avoiding plasma and coagulation abnormalities. According to the
      literature, long-term patient and graft survival rates are similar to those
      achieved with ABO-compatible kidney transplants. We have used selective
      immunoadsorption in two ABO-incompatible kidney transplants performed at our
      institution. No acute rejection was observed at 12 and 32 months' follow-up and
      both grafts are functioning well. Despite the widespread use of ABO-incompatible
      kidney transplant, however, the mechanisms of accommodation, the best
      desensitization protocol, the upper baseline and perioperative isoagglutinin
      titer limit, and the most accurate isoagglutinin measurement assay are still to
      be defined.

PMID- 22388827
TI  - [Multimodal treatment for acute antibody-mediated renal transplant rejection:
      successful rescue therapy with combined plasmapheresis, photopheresis and
      intravenous immunoglobulin].
AB  - The fundamental role of antibodies in the development of acute graft rejection
      has been established recently. Antibody-mediated acute rejection may develop at
      any time during the post-transplant period. Several therapeutic approaches have
      been proposed in the last decades. However, there is no standardized therapy. The
      aim of this study is to report the Sapienza University experience of combined
      plasma treatment and high-dose intravenous immunoglobulin +/- extracorporeal
      photopheresis. From January 2006 to September 2009, 6 patients were treated at
      Sapienza University. In 5 cases (83%) complete regression of the acute rejection
      was observed, followed by stable renal function (median creatinine value at 1
      year follow-up: 1.5 mg/dL). No adverse events were reported. Our approach seems
      to give good results in terms of graft survival and procedure safety. Further
      studies on a larger number of patients will be needed to confirm the validity of
      these findings. Moreover, comparison between our protocol and other treatments is
      necessary.

PMID- 22388828
TI  - [New therapeutic prospects for renal transplant: extracorporeal
      photochemotherapy].
AB  - Since 1960, different classes of immunosuppressive drugs have been used in the
      post-transplant follow-up. Each is assessed for its effectiveness in preventing
      rejection but also on the basis of the many side effects induced by prolonged
      treatment. To reduce these side effects, continuous development of knowledge and
      medical technology to create cutting-edge therapies in the field is necessary.
      One of these is extracorporeal photochemotherapy (ECP), an immunomodulatory
      therapy approved by the United States Food and Drug Administration in 1988 for
      the treatment of advanced forms of cutaneous T-cell lymphoma. EC P is a useful
      therapeutic tool for the development of immunomodulation supported by CD8+ clone
      specific cytotoxic lymphocytes. The T cells targeted by EC P are modified by
      photoactivation and seem to develop marked immunogenicity with no suppression of
      the immune response. Recent studies suggest the possible utility of EC P in the
      treatment of glomerulonephritis and in countering rejection after transplantation
      of organs including the kidney.

PMID- 22388829
TI  - [Therapeutic plasma exchange: a review of the literature].
AB  - Therapeutic plasma exchange is an extracorporeal plasmapheresis method for
      removing high-molecular-weight pathogens and toxins from the circulation. It can
      be indicated in many clinical conditions, both kidney-related and non-kidney
      related. This review focuses on clinical trials related to Goodpasture syndrome,
      thrombotic thrombocytopenic purpura, and acute renal insufficiency due to
      multiple myeloma. It also discusses the difficulties and opportunities associated
      with the development of a randomized controlled multicenter study and of a web
      based database. Finally, we report a summary of the risks and complications of
      therapeutic plasma exchange and how we can update the information on their
      frequency and seriousness by means of a longitudinal prospective multicenter
      study open to all centers performing the procedure.

PMID- 22388830
TI  - [Use of virus-inactivated plasma in apheresis treatment of thrombotic
      thrombocytopenic purpura: preliminary data].
AB  - Plasma exchange (TPEx) with fresh frozen plasma (FFP) or cryosupernatant plasma
      infusion is the treatment of choice for thrombotic thrombocytopenic purpura
      (TTP). The authors evaluate the preliminary data of the multicenter SIdEM study
      that compares virus-inactivated plasma with fresh frozen plasma (FFP) or
      cryosupernatant plasma in the apheretic treatment of TTP.

PMID- 22388831
TI  - [Role of antibodies in kidney transplant].
AB  - Rejection is one of the most frequent causes of graft loss after a kidney
      transplant. In this context, in the last few years the essential role of
      antibodies in the anti-graft immune response has become more evident. Antibody
      mediated damage has been classified into four histological patterns: hyperacute
      rejection, caused by the presence of pre-existing donor-specific antibodies
      directed against HLA or non-HLA antigens; acute antibody-mediated rejection,
      usually due to antibodies elicited following transplantation; chronic antibody
      mediated rejection, which can develop months or years after the first appearance
      of circulating antibodies; and Cd4 deposition without morphologic evidence of
      active rejection, previously described as ''accommodation''. In recent years,
      thanks to the development of specific desensitization protocols, it has become
      possible to transplant patients sensitized to donor HLA antigens. Recently,
      besides consolidated protocols which include immunoglobulin administration
      associated or not with plasmapheresis, novel approaches of therapeutic apheresis
      with specific removal of antibodies and bortezomib, an agent that can efficiently
      decrease donor-specific antibody levels, have been developed. As far as the
      treatment of antibody-mediated rejection is concerned, different
      immunosuppressive strategies have been used. These include the combination of
      immunoglobulin administration and plasmapheresis with or without the use of an
      anti-CD20 monoclonal antibody. More recently, an innovative therapy with
      eculizumab has proved to be very effective against acute antibody-mediated
      rejection. The debate regarding the cause-effect relationship between the
      development of an early post-transplant humoral immune response in patients with
      stable graft function and premature graft loss remains open to discussion.
      Clinical studies are underway to provide an adequate answer to this question. In
      conclusion, comprehension of the fundamental role of antibodies and the
      consolidation of desensitization techniques together with early treatment of
      antibody-mediated rejection remain important objectives to improve long-term
      allograft survival.

PMID- 22388832
TI  - [Granulocyte-monocyte apheresis for the treatment of inflammatory bowel disease].
AB  - We review the available literature on granulocyte-monocyte apheresis for the
      treatment of inflammatory bowel disease and report the outcome data of a
      multicenter observational study from the Italian registry for therapeutic
      apheresis.

PMID- 22388833
TI  - [Early use of polymyxin B in sepsis].
AB  - During sepsis, lipopolysaccharide released by gram-negative bacteria induces
      activation of inflammatory pathways resulting in organ dysfunction and failure.
      Extracorporeal therapies that remove this molecule and support organ function are
      useful in critically ill patients in ICUs. Today, blood purification therapies
      such as high-volume hemofiltration, polymyxin B hemoperfusion, and coupled plasma
      filtration adsorption are easy to perform. According to the reconciliation of the
      three sepsis theories and thanks to the removal of lipopolysaccharide (the first
      inflammatory stimulus) from the blood, we can provide an effective and useful
      extracoporeal therapy for this clinical condition.

PMID- 22388834
TI  - [Therapeutic apheresis in idiopathic nephrotic syndrome].
AB  - Idiopathic nephrotic syndrome (INS) is characterized by diffuse foot process
      effacement on electron microscopy and minimal changes (called minimal change
      nephropathy [MCN]), focal segmental glomerular sclerosis (FSGS), or the mesangial
      variant with proliferation on light microscopy. No evidence of immune deposits is
      seen. MCN is the most common form of INS in children and is sensitive to
      corticosteroid therapy in 90% of cases. FSGS accounts for 20-30% of biopsy-proven
      glomerulopathies in adult patients. Fifty percent of drug-resistant patients
      develop terminal renal failure in 6-8 years. Moreover, FSGS reappears in 15-50%
      of cases after the first transplant and in a higher percentage after the second
      graft. Genetic forms of INS, with mutation of the NPHS1 and NPHS2 genes encoding
      nephrin and podocin, are mostly steroid resistant and very rarely recur in the
      transplant. On the basis of any clinical pattern they are indistinguishable from
      idiopathic forms. Sera from patients with FSGS may contain some proteinuric or
      permeability factors (PFs), which have been partially identified and are
      predictive of recurrence in kidney grafts. Removal of PFs by means of
      plasmapheresis or plasma immunoadsorption by protein A or LDL apheresis has been
      associated with proteinuria reduction in cases of FSGS both of native and
      transplanted kidneys, in small series or cohort studies described by many
      authors. In this review of the main studies we will analyze the results of the
      apheretic treatments and the role of some clinical, serological and histological
      parameters in determining the outcome of patients.

PMID- 22388835
TI  - [Apheresis in the treatment of vasculitis].
AB  - ANCA-associated vasculitides are a group of inflammatory diseases affecting
      medium and small vessels with a redundant and hence complex pathogenetic
      mechanism. Since their first identification, their dismal prognosis has forced
      researchers to find effective therapies. The prognosis has changed since the
      advent of immunomodulatory drugs like steroids, cyclophosphamide, azathioprine,
      mycophenolate mofetil and, more recently, biological drugs. Plasmapheresis in
      association with immune suppressant drugs has shown beneficial effects in some
      clinical trials, mostly in dialysis-dependent patients. Apheresis should remove,
      in a nonselective manner, pathogenetic antibodies like ANCA but also immune
      complexes, cytokines and inflammatory mediators. A recent meta-analysis took into
      account 28 randomized clinical trials studying therapeutic interventions in adult
      vasculitis with renal involvement, six of them scheduling plasmapheresis as
      adjunctive therapy to immune suppressant drugs. This association significantly
      reduced the need for dialysis at three (1 trial: RR 0.45, 95% CI 0.24-0.84) and
      twelve (5 trials: RR 0.47, 95% CI 0.3-0.75) months but not the mortality at one
      year. We can conclude that plasmapheresis is an effective treatment option for
      vasculitides with severe renal failure. It can also be considered in case of
      ineffectiveness of or contraindications to standard treatment.

PMID- 22388836
TI  - [Apheresis in antiphospholipid syndrome (APS)].
AB  - Antiphospholipid syndrome (APS) is a rare clinical disorder characterized by
      thromboembolic manifestations and/or obstetric complications. Along with the
      clinical symptoms and signs, serum antiphospholipid antibodies have to be
      detected. APS can be primary, i.e., without any concomitant disorders, or
      secondary to other autoimmune diseases, particularly systemic lupus
      erythematosus. Criteria for the diagnosis of APS have been clearly established.
      Hyperacute APS (or catastrophic antiphospholipid syndrome), often with a poor
      prognosis, must meet four criteria: involvement of three or more organs, rapid
      evolution of clinical manifestations, microangiopathic occlusion of small blood
      vessels at biopsy, and presence of antiphospholipid antibodies. The rationale for
      apheresis treatment is the removal of pathogenetic antibodies involved in the
      development of tissue damage. Our experience includes 23 patients, in particular
      15 women treated for 19 pregnancies. According to the National Guidelines
      Program, the effectiveness of apheresis in catastrophic syndrome has a level of
      evidence of V/VI, with a strength of recommendation A; in highrisk pregnancy it
      has a level of evidence of V with a strength of recommendation B. It will be
      necessary to better define the prognosis of various categories of pregnant
      patients with APS, as well as useful laboratory parameters to monitor its
      clinical course and anticipate any complications of pregnancy.

PMID- 22388837
TI  - [Pathogenesis of systemic lupus erythematosus (LES)].
AB  - The refinement of our knowledge of the functioning of the immune system, both
      innate and adaptive, in the last decade has fundamentally modified the
      interpretation of the pathogenesis of systemic lupus erythematosus (SLE). In this
      autoimmune disease the main pathogenetic mechanism leads to the production of
      autoantibodies specific to self antigens (tolerated or not) favored by a genetic
      condition and triggered by endogenous factors, such as estrogens or exposure to
      sunlight, and exogenous factors, such as viruses. T cells were thought to play a
      predominant role. The identification of a population of B cells located in
      marginal areas of the germinal centers and equipped with receptors belonging to
      the family of Toll-like receptors (TLR) (either extracellular, such as TLR4, or
      intracellular, such as TLR3, which recognize DNA and RNA) and High Mobility Box
      Protein 1 (HMBP1), capable in a T-independent manner of self-reactive activities
      with IgG autoantibody production and release, has greatly advanced the
      understanding of the pathogenesis of SLE. The T and B lymphocyte populations
      interact in complex ways, with interference of tolerance-inducing regulatory T
      cells and inflammation-inducing Th17 cells, finely regulating the cross-talk in
      the lymphocyte system. This review will discuss the latest knowledge on the
      pathogenesis of SLE.

PMID- 22388838
TI  - [Plasmapheresis in intensive care].
AB  - Blood purification by means of plasmapheresis has been known since the 1950s.
      Plasmapheresis first separates plasma from the blood's cell component; in the
      classical plasma exchange modality, the patient's plasma is then replaced with
      fresh frozen plasma from a donor. This procedure is still current in different
      fields of medicine, as there are hematological (thrombotic thrombocytopenic
      purpura, Waldenstrom's disease), neurological (Guillain-Barre' syndrome,
      myasthenia gravis) and toxicological indications (several forms of mushroom
      poisoning, tricyclic antidepressants, transfusional reactions), as well as
      nephrological indications (Goodpasture's syndrome, ANCA-associated vasculitis,
      myeloma) for its use. Many of these diseases are encountered in the intensive
      care setting due to the organ dysfunction they may cause. In recent years,
      purification procedures have been developed that avoid the replacement of plasma
      by purifying plasma directly. Once treated, the plasma can be returned to the
      patient, thereby avoiding the loss of factors like vitamins, coagulation
      proteins, and antibodies and at the same time reducing the possible risk of
      infection. The technological prerequisite is the use of cartridges containing
      absorbent material (resins) on which the plasma obtained from the plasma
      separation is perfused. The physicochemical characteristics of the resins allow
      them to trap large-sized or protein-bound solutes. Such procedures have found
      particular application in two fields typically related to intensive care: liver
      failure and sepsis. The future of plasmapheresis seems oriented towards
      increasingly selective treatments capable of removing only those molecules that
      are the cause or associated cause of the damage.

PMID- 22388840
TI  - [Adacolumn apheresis for hepatitis C virus in patients waiting for kidney
      transplant. Preliminary study].
AB  - Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis
      population than in the general population. Patients with chronic kidney disease
      with persistent HCV infection may develop serious and progressive chronic liver
      disease, with associated long-term morbidity and mortality related to cirrhosis
      and hepatocellular carcinoma. Monocytes and macrophages are known to produce
      extrahepatic breeding sites and spread the disease. Our aim was to lower the
      levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia
      using an extracorporeal device: the Adacolumn (r) leukocyte apheresis system
      (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The
      column is a single-use (disposable) polycarbonate column with a capacity of about
      335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in
      physiological saline. The carriers adsorb ''activated'' granulocytes and
      monocytes/macrophages that bear Fc and complement receptors. The patients
      underwent five 1-hour sessions for five consecutive days. The column was placed
      in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of
      60 minutes. A reduction of viremia was observed in all patients in association
      with a decrease in cytokine levels and a proportional decrease in immune cells.
      Although this study investigated responses in a small number of patients, it was
      shown that the Adacolumn changed the cellular immunity and promoted early viral
      response.

PMID- 22388839
TI  - [Chronic hepatitis C virus infection: clinical picture and treatment
      possibilities].
AB  - It has been estimated that between 1.5 and 2 million people in Italy have anti
      HCV antibodies. The vast majority are chronically infected with HCV and are
      unaware of the infection. Chronic hepatitis C is asymptomatic during most of its
      course, which lasts decades. The diagnosis is based on anti-HCV antibodies and,
      subsequently, an HCV-RNA test, to be performed in all subjects with persistently
      elevated ALT and in those who are at risk of HCV infection. The identification of
      infected subjects allows prophylaxis of advanced liver disease, cirrhosis and
      hepatocellular carcinoma by antiviral treatment, which is effective in about 50%
      of patients. The current standard of care for chronic HCV infection is the
      combination of pegylated interferon and ribavirin. Their dosage and the duration
      of therapy are tailored to the HCV genotype and the time to viral response. The
      frequent occurrence of adverse events, mainly hematological, requires careful
      monitoring, dose reduction in some cases, and, rarely, the use of erythrocyte or
      leukocyte growth factors. A new class of drugs for HCV treatment, the direct
      acting antivirals, is currently under development. Two of these drugs, the viral
      protease inhibitors boceprevir and telaprevir, are awaiting registration in
      Europe for use in association with pegylated interferon and ribavirin. These
      drugs are expected to ameliorate the virus eradication rates in patients who have
      not received previous antiviral treatment and, more importantly, to accomplish
      effective treatment in those patients who are partial responders to the current
      standard of care.

PMID- 22388841
TI  - [Effects of cascade filtration in combination with interferon and ribavirin in
      the treatment non responder chronic hepatitis C patients].
AB  - In 40% of patients with chronic hepatitis C, standard therapy is unable to
      eradicate the virus. Since the response to pharmacological treatment depends on
      the initial viral load, there is a rationale for reducing this load by means of
      apheretic depletion of the C virus. The aim of this work was to administer
      cascade filtration (CF) to non responder patients affected by hepatitis C (pts)
      before resuming the pharmacological treatment. 10 pts underwent 12 sessions of
      CF, 3 per week (treated plasma volume/session: 3000 mL). After the first week,
      therapy with PEG-IFN (1.5 ug/Kg/week) plus Ribavirin (1200 mg/day) was added. The
      viral load was determined before and after each CF session, and at the 1st, 3rd
      and 6th month. The mean pre-apheresis viral load dropped from 2176275+/-3109997
      U/mL at the first session to 1486726+/-2091975 U/mL by the fourth (p<0.001), and
      347500+/-637428 U/mL before the last (p<0.001). The mean percentage reduction of
      the viral load went from a minimum of 29.5% to a maximum of 42%. Early viral
      response (EVR) was obtained in 70% of these patients as compared with only 10% in
      an age- and sex-matched control group consisting of 10 patients. Unfortunately,
      we did not get the same good results in terms of sustained viral response (SVR:
      10% in apheretic patients vs 0% in the control group). Efficacious removal of HCV
      was obtained with CF. However, the successful reduction in the viral load
      achieved with apheresis in terms of EVR was not confirmed when we considered the
      SVR.

PMID- 22388842
TI  - [Apheresis in dermatologic diseases].
AB  - This report discusses the different types of apheresis used to treat skin
      diseases and focuses specifically on photopheresis or ECP (extracorporeal
      photochemotherapy). ECP is a systemic immunomodulatory therapy used successfully
      to treat many different, mainly autoimmune diseases such as cutaneous T-cell
      lymphomas, graft-versus-host disease, systemic sclerosis, atopic dermatitis, and
      pemphigus vulgaris. It has also proved effective against graft rejection after
      transplant. The exact mechanism by which the ECP performs its therapeutic
      activity is not yet entirely clear. However, at least 2 mechanisms have been
      identified that may explain the therapeutic effect. Firstly, ECP is able to
      induce downregulation of the self-allogeneic immune response that occurs in graft
      versus-host disease, systemic sclerosis and atopic dermatitis, and secondly, it
      can stimulate an immune response against the neoplastic clones in patients with
      cutaneous T-cell lymphomas. At the Dermatology Clinic of the University of Siena,
      more than 100 patients with different immune-mediated diseases were treated with
      ECP. The results obtained are very interesting and our 20 years of experience
      confirm that the treatment is well tolerated. ECP can therefore be considered of
      great utility in the modulation of the immune system.

PMID- 22388843
TI  - [Apheresis in children: procedures and outcome].
AB  - Apheresis procedures are used in children to treat an increasing number of
      conditions by removing different types of substances from the bloodstream. In a
      previous study we evaluated the first results of our experience in children,
      emphasizing the solutions adopted to overcome technical difficulties and to adapt
      adult apheresis procedures to a pediatric population. The aim of the present
      study is to present data on a larger number of patients in whom apheresis was the
      main treatment. Ninety-three children (50 m, 43 f) affected by renal and/or
      extrarenal diseases were included. They were treated with LDL apheresis, protein
      A immunoadsorption, or plasma exchange. Our therapeutic protocol was the same as
      described in the previous study. Renal diseases and immunological disorders
      remained the most common conditions requiring this therapeutic approach. However,
      hemolytic uremic syndrome (HUS) was no longer the most frequent renal condition
      to be treated, as apheresis is currently the first treatment option only in cases
      of atypical HUS. In this series we also treated small children, showing that low
      weight should no longer be considered a contraindication to apheresis procedures.
      The low rate of complications and the overall satisfactory clinical results with
      increasingly advanced technical procedures make a wider use of apheresis in
      children realistic in the years to come.

PMID- 22388844
TI  - [Plasmapheresis in central nervous system disorders].
AB  - Therapeutic plasmapheresis (TPE) has an established role in disorders of the
      peripheral nervous system, but its use in disorders of the central nervous system
      (CNS) does not rely upon evidence-based data. Nevertheless, TPE is currently used
      in severe acute forms of demyelinating disease (multiple sclerosis/acute
      encephalomyelitis) unresponsive to corticosteroids. Recently, antibodies against
      the water channel aquaporin-4 have been detected in patients affected by
      neuromyelitis optica (Devic syndrome) and their pathogenetic role has been
      demonstrated, supporting the use of TPE in this disease. TPE has been reported to
      be effective in some patients affected by stiff-person syndrome or limbic
      encephalitis associated with antibodies against voltagegated potassium channels.
      TPE has also been used in selected patients with treatment-resistant epilepsy or
      status epilepticus within complex syndromes of various etiologies. The available
      data still do not support the use of TPE in most paraneoplastic disorders of the
      CNS.

PMID- 22388845
TI  - [LDL-apheresis in patients with familial autosomal recessive
      hypercholesterolemia].
AB  - LDL-apheresis reduces the cardiovascular risk in patients with familial
      hypercholesterolemia. The addition of statin therapy in patients with autosomal
      recessive hypercholesterolemia may change the lipid profile to a less atherogenic
      pattern.

PMID- 22388846
TI  - [Treatment of sudden sensorineural hearing loss (SSHL) with HELP-apheresis: our
      experience].
AB  - In a specific group of patients affected by sudden sensorineural hearing loss
      (SSHL) with high plasma levels of LDL-cholesterol and/or fibrinogen, HELP
      apheresis treatment makes a difference in hearing recovery and is a further
      option available in SSHL therapy.

PMID- 22388847
TI  - [Leukapheresis and chronic inflammatory bowel disease: an additional obligation
      for the nephrologist].
AB  - The current treatment of chronic inflammatory bowel diseases involves the
      administration of different immunosuppressive drugs, whose use is associated with
      several side effects. Among the treatment alternatives, clinicians are attracted
      by leukapheresis, a method able to selectively remove from the circulation
      molecules involved in the onset and maintenance of inflammation. From 2007 to
      2008, six patients were recruited from our clinics; four patients were affected
      by ulcerative colitis and two by Crohn's disease. They presented symptoms
      including abdominal pain and diarrhea despite treatment with steroids and
      sulfasalazine. Leukapheresis sessions were performed weekly (1 hour/week) for
      five consecutive weeks. The leukapheresis sessions resulted in a significant
      improvement in the patients' clinical as well as general conditions. The
      abdominal pain disappeared and significant reduction of diarrhea and fecal
      calprotectin levels was observed. No side effects occurred. The clinical benefits
      were supported by resolution of ulcerative lesions. After six months of follow-up
      no disease relapse was observed. The leukapheresis treatment has also prevented
      surgical interventions in all patients enrolled in the study. Our results suggest
      that leukapheresis may be helpful in patients affected by inflammatory bowel
      diseases, allowing early reduction of immunosuppressive drug administration.

PMID- 22388848
TI  - [Predictors of clinical response in patients with ulcerative colitis treated with
      granulocyte-monocyte apheresis: analysis of the apheresis registry data].
AB  - We analyzed predictors of clinical response after a cycle of granulocytemonocyte
      apheresis in 173 patients with ulcerative colitis. Hemoglobin levels
      independently predicted good clinical outcome.

PMID- 22388849
TI  - [Lyell's syndrome: proposal for a therapeutic protocol].
AB  - Toxic epidermal necrolysis or Lyell's syndrome is a life-threatening, drug
      induced disorder characterized by severe epidermal injury. Although
      plasmapheresis is expensive and requires easy venous access, it could be included
      in the first-line treatment of toxic epidermal necrolysis. The method is safe and
      effective, providing prompt relief from pain and rapid cessation of necrolysis.
      Moreover, in our experience plasmapheresis could be used in patients who were
      unresponsive to corticosteroids, and in patients with severe clinical symptoms.

PMID- 22388850
TI  - [CPFA (coupled plasma filtration absorption) treatment of septic shock. A
      retrospective study of nine patients].
AB  - Coupled plasma filtration absorption (CPFA) can increase blood pressure in septic
      shock and reduce fever during and after treatment. It is not able to stop the
      activation of intravascular coagulation and does not reduce the need for dialysis
      or the overall mortality.

PMID- 22388862
TI  - Expression of human CD46 has no effect on porcine circovirus type 2 infection and
      shedding in the experimental pig model.
AB  - Xenotransplantation of tissues from transgenic pigs with desired genetic
      modifications such as CD46 expression help minimize xenograft rejections.
      However, CD46 is a known receptor for some viruses. In this study, pigs
      transgenic for human CD46 (CD46-TG) and appropriate non-transgenic (non-TG)
      control pigs were utilized to determine possible differences in the level of
      replication and shedding of porcine circovirus type 2 (PCV2). Non-TG and CD46-TG
      were blocked by transgenic status and randomly divided into three groups: Non-TG
      negative controls (n = 3), non-TG-PCV2 (n = 10; PCV2a = 5, PCV2b = 5), and CD46
      TG-PCV2 (n = 6; PCV2a = 3, PCV2b = 3). Blood, oral, nasal and fecal swabs were
      collected at regular intervals from the day of arrival until 70 days post
      inoculation (DPI). All samples were tested by quantitative real-time PCR for the
      presence of PCV2 DNA and serum was tested for presence of PCV2 antibodies by
      ELISA. Overall, the main effects "transgenic status" and "PCV2 subtype" had no
      influence on degree of PCV2 viremia and shedding or the anti-PCV2 humoral immune
      response in CD46-TG-PCV2 pigs compared to non-TG-PCV2 pigs. Differences in PCV2
      concentrations between non-TG-PCV2 and CD46-TG-PCV2 pigs were minimal and limited
      to DPI 35 in sera, DPI 7 in fecal swabs and DPI 5 in nasal swabs when CD46-TG
      PCV2 pigs had significantly higher concentrations of PCV2 DNA. At DPI 1, CD46-TG
      PCV2 pigs had significantly lower concentrations of PCV2 DNA in oral swabs. Under
      the study conditions, the presence of human CD46 in transgenic pigs had no effect
      on PCV2 infection in otherwise healthy pigs capable of a normal immune response.

PMID- 22388863
TI  - New secrets of spider silk: exceptionally high thermal conductivity and its
      abnormal change under stretching.
AB  - Two new significant discoveries are reported: i) the dragline silk of N. clavipes
      spider has an exceptionally high thermal conductivity: up to 416 W/m.K that beats
      most materials; ii) contrary to normal materials, its thermal conductivity
      increases with strain (19% increase under ~20% strain). These new findings will
      revolutionize the design of polymer fibers to increase their thermal conductivity
      by orders of magnitude.

PMID- 22388864
TI  - Landmark/Image-based Deformable Registration of Gene Expression Data.
AB  - Analysis of gene expression patterns in brain images obtained from high
      throughput in situ hybridization requires accurate and consistent annotations of
      anatomical regions/subregions. Such annotations are obtained by mapping an
      anatomical atlas onto the gene expression images through intensity- and/or
      landmark-based registration methods or deformable model-based segmentation
      methods. Due to the complex appearance of the gene expression images, these
      approaches require a pre-processing step to determine landmark correspondences in
      order to incorporate landmark-based geometric constraints. In this paper, we
      propose a novel method for landmark-constrained, intensity-based registration
      without determining landmark correspondences a priori. The proposed method
      performs dense image registration and identifies the landmark correspondences,
      simultaneously, using a single higher-order Markov Random Field model. In
      addition, a machine learning technique is used to improve the discriminating
      properties of local descriptors for landmark matching by projecting them in a
      Hamming space of lower dimension. We qualitatively show that our method achieves
      promising results and also compares well, quantitatively, with the expert's
      annotations, outperforming previous methods.

PMID- 22388865
TI  - Curcumin induces autophagy in ACC-MESO-1 cells.
AB  - Malignant pleural mesothelioma is known to be widely resistant to therapy and new
      treatment strategies are needed. Curcumin, which has a long history as a dietary
      spice is known to suppress the growth of multiple cancer lines, but the effects
      on mesothelioma cells are not well defined. In the present study we examined the
      effects of curcumin on ACC-MESO-1, which is a human derived mesothelioma cell
      line. We found that curcumin dose-dependently reduced cell viability but did not
      induce apoptosis. Curcumin administration increased LC3B-II/LC3B-I expression,
      and induced the formation of autophagosomes on electron microscopy. These changes
      were attenuated by RNA silencing of atg5. From these findings it was speculated
      that induction of autophagy was at least in part involved in the reduction of
      cell viability by curcumin.

PMID- 22388866
TI  - Molecular chirality and chiral capsule-type dimer formation of cyclic triamides
      via hydrogen-bonding interactions.
AB  - Chiral properties of bowl-shaped cyclic triamides bearing functional groups with
      hydrogen-bonding ability were examined. Chiral induction of cyclic triamide 3a
      was observed by addition of chiral amine in solution, and chiral separation was
      achieved by simple crystallization to afford chiral capsule-type dimer structure
      of 4a.

PMID- 22388867
TI  - Hydrophobin genes of the entomopathogenic fungus, Metarhizium brunneum, are
      differentially expressed and corresponding mutants are decreased in virulence.
AB  - Hydrophobins are small, cysteine-rich, secreted proteins, ubiquitously produced
      by filamentous fungi that are speculated to function in fungal growth, cell
      surface properties, and development, although this has been rigorously tested for
      only a few species. Herein, we report identification of three hydrophobin genes
      from the entomopathogenic fungus, Metarhizium brunneum, and functional
      characterization of strains lacking these genes. One gene (HYD1/ssgA) encodes a
      class I hydrophobin identified previously. Two new genes, HYD3 and HYD2, encode a
      class I and class II hydrophobin, respectively. To examine function, we deleted
      all three separately, from the M. brunneum strain KTU-60 genome, using
      Agrobacterium tumefaciens-mediated transformation. Deletion strains were screened
      for alterations in developmental phenotypes including growth, sporulation,
      pigmentation, colony surface properties, and virulence to insects. All deletion
      strains were reduced in their ability to sporulate and showed alterations in wild
      type pigmentation, but all retained wild-type hydrophobicity, except for one
      individual hyd3 mutant. Complementation with the wild-type HYD3 gene restored
      hydrophobicity. Each gene, present as a single copy in the genome, showed
      differential expression patterns dependent on the developmental stage of the
      fungus. When Spodoptera exigua (beet armyworm) larvae were treated with either
      conidia or blastospores of each hyd mutant, reductions in virulence and delayed
      mortality were observed as compared to WT. Together, these results suggest that
      hydrophobins are differentially expressed and may have distinct, but compensating
      roles, in conidiation, pigmentation, hydrophobicity, and virulence.

PMID- 22388869
TI  - Advancing prediction of tissue distribution and volume of distribution of highly
      lipophilic compounds from a simplified tissue-composition-based model as a
      mechanistic animal alternative method.
AB  - It has been reported that values of tissue-plasma ratios (K(p)) and resulting
      volume of distribution at steady state (V(ss)) are substantially overpredicted
      for several highly lipophilic drugs. This effect was observed particularly with
      the published version of the tissue-composition-based model, which used
      experimentally determined unbound fraction in plasma (fu(p)) as input for drugs.
      The reasons for the unreasonably high V(ss) predictions were investigated in this
      study for 14 highly lipophilic compounds with a log n-octanol-water partition
      coefficient (log P(ow)) of at least 5.8. Here, we argue that the experimentally
      determined fu(p) is inaccurate for these compounds, which affected the prediction
      of K(p) and V(ss). Alternatively, the tissue-plasma ratio of neutral lipids (nl)
      equivalent was used as the main factor governing K(p), and hence V(ss), in
      addition to log P(ow). The average fold error of deviation between the predicted
      and observed human V(ss) is 124 for the published model, whereas it significantly
      decreased to 1.5 for the proposed model. The sensitivity analysis confirmed the
      importance of nl content and drug lipophilicity. Overall, this study proposes a
      generic and simplified tissue-composition-based model for highly lipophilic drugs
      and chemicals, which is a step forward toward improving prediction of V(ss) into
      physiologically based pharmacokinetic (PBPK) models.

PMID- 22388868
TI  - Transient and multivariate system for transformation of a fungal plant pathogen,
      Rosellinia necatrix, using autonomously replicating vectors.
AB  - Rosellinia necatrix is a fungus that infects a wide range of host plants and
      ruins a variety of commercially important crops. DNA fragments can be introduced
      into R. necatrix using conventional protoplast-PEG transformation and genome
      integrating vectors; however, transformation efficiency with this strategy is
      quite low. Therefore, to establish a more effective transformation system for the
      studies of R. necatrix, an autonomously replicating vector was constructed using
      AMA1 sequences derived from Aspergillus nidulans, which is distantly related to
      R. necatrix. Use of this vector with AMA1 sequences increased transformation
      efficiency in R. necatrix, and the vector was maintained as a plasmid in the
      transformants. Transient and multivariate functional analyses in R. necatrix were
      performed using co-transformation of multiple pAMA-H vectors, which each carried
      either an expression cassette for eGFP, mOrange2, or a geneticin resistance gene.
      Furthermore, fluorescent proteins expressed from the autonomously replicating
      vectors were dispersed throughout fungal colonies even though the vectors
      themselves were restricted to the center of each colony. This intriguing
      phenomenon indicated that gene products could move from the center to the margin
      in a colony of the filamentous fungi via a cell-to-cell transport system.

PMID- 22388870
TI  - Potentiation of synaptic strength and intrinsic excitability in the nucleus
      accumbens after 10 days of morphine withdrawal.
AB  - Neuroadaptations in the nucleus accumbens (NAc) are associated with the
      development of drug addiction. Plasticity in synaptic strength and intrinsic
      excitability of NAc medium spiny neurons (MSNs) play critical roles in addiction
      induced by different classes of abused drugs. However, it is unknown whether
      morphine exposure influences synaptic strength, intrinsic excitability or both in
      NAc. Here we show that chronic withdrawal (10 days after the last injection) from
      repeated morphine exposure elicited potentiation in both glutamatergic synaptic
      strength and intrinsic excitability of MSNs in NAc shell (NAcSh). The
      potentiation of synaptic strength was demonstrated by an increase in the
      frequency of miniature excitatory postsynaptic currents (mEPSCs), a decrease in
      the paired-pulse ratio (PPR), and an increase in the ratio of alpha-amino-3
      hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR)- to N-methyl-D
      aspartate receptors (NMDAR)-mediated currents. The potentiation of intrinsic
      excitability was mediated by inhibition of the sustained potassium currents via
      extrasynaptic NMDAR activation. The function of the presynaptic group II
      metabotropic glutamate receptors (mGluR2/3) was downregulated, enhancing the
      probability of glutamate release on synaptic terminals during chronic morphine
      withdrawal. Pretreatment with the mGluR2/3 agonist LY379268 completely blocked
      potentiation of both synaptic strength and intrinsic excitability. These results
      suggest that chronic morphine withdrawal downregulates mGluR2/3 to induce
      potentiation of MSN glutamatergic synapse via increased glutamate release,
      leading to potentiation of intrinsic excitability. Such potentiation of both
      synaptic strength and intrinsic excitability might contribute to neuroadaptations
      induced by morphine application.

PMID- 22388871
TI  - Rediscovering cobalt's surface chemistry.
AB  - Cobalt is an active metal for a variety of commercially and environmentally
      significant heterogeneously catalysed processes. Despite its importance, Co's
      surface chemistry is less studied compared to other key industrial catalyst
      metals. This stems in part from the difficulties associated with single crystal
      preparation and stability. Recent advances in scanning probe microscopy have
      enabled the atomic scale study of the structural, electronic, and magnetic
      properties of well-defined Co nanoparticles on metal substrates. Such systems
      offer an excellent platform to investigate the adsorption, diffusion,
      dissociation, and reaction of catalytically relevant molecules. Here we discuss
      the current understanding of metal-supported Co nanoparticles, review the limited
      literature on molecular adsorption, and suggest ways that they can be used to
      explore Co's rich surface chemistry. Our discussion is accompanied by new high
      resolution scanning tunnelling microscopy data from our group, which illustrate
      some of the interesting properties of these complex systems.

PMID- 22388872
TI  - Adequacy of family history taking in ovarian cancer patients: a population-based
      study.
AB  - The aim of this study was to evaluate the adequacy of family history taking in
      epithelial ovarian cancer (EOC) patients and to identify factors that determine
      adequacy. Furthermore, the validity of family history taking was assessed by
      comparison with self-administered questionnaires. Medical records of all 1,112
      EOC patients registered by the nation-wide cancer registry and diagnosed in
      eleven Dutch hospitals between 1996 and 2006 were reviewed. Adequate family
      history taking was defined as a written notification of the presence or absence
      of relatives with breast or ovarian cancer. Factors that were correlated with
      family history taking were identified using univariable and multivariable
      logistic regression. 147 patients filled in a postal questionnaire. An adequate
      family history was taken in 41% of all cases. Younger age, an academic hospital
      and having undergone surgery and/or chemotherapy were associated with adequate
      family history taking. The comparison with self-administered questionnaires
      showed a disagreement in 64% mainly due to missing data in medical records.
      Documentation on family history is either absent or inadequate in the medical
      records in the majority of EOC patients. These data urge for better uptake of
      hereditary cancer risk assessment. Different strategies for this assessment like
      improved family history taking and genetic testing in EOC patients should be
      explored.

PMID- 22388873
TI  - Familial gastric cancer: guidelines for diagnosis, treatment and periodic
      surveillance.
AB  - Hereditary diffuse gastric cancer (HDGC) is a relatively rare disorder, with a
      mutated CDH1 gene as the only known cause. Carriers of a germline mutation in
      CDH1 have a lifetime risk of >80% of developing diffuse gastric cancer. As
      periodic gastric surveillance is of limited value in detecting early stages of
      HDGC, prophylactic gastrectomy is advised for this patient group. Little is known
      about other types of familial gastric cancer. The Dutch working group on
      hereditary gastric cancer has formulated guidelines for various aspects of
      medical management for families and individuals at high risk of developing
      gastric cancer, including criteria for referral, classification, diagnostics, and
      periodic gastric surveillance. These guidelines are not limited to HDGC and are
      therefore partially complementary to the guidelines on hereditary diffuse gastric
      cancer of the international gastric cancer linkage consortium (IGCLC 2010). In
      order to optimize the care and increase the knowledge on hereditary gastric
      cancer it is important to centralize medical care for these patients. National
      and international collaboration is warranted to improve the quality of research
      by increasing the size of study cohorts.

PMID- 22388874
TI  - Statement on the publication of Alice Dreger's investigation, Darkness's descent
      on the American Anthropological Association: a cautionary tale.

PMID- 22388875
TI  - An introduction to the special issue on middle childhood.

PMID- 22388876
TI  - Middle childhood and modern human origins.
AB  - The evolution of modern human life history has involved substantial changes in
      the overall length of the subadult period, the introduction of a novel early
      childhood stage, and many changes in the initiation, termination, and character
      of the other stages. The fossil record is explored for evidence of this
      evolutionary process, with a special emphasis on middle childhood, which many
      argue is equivalent to the juvenile stage of African apes. Although the
      "juvenile" and "middle childhood" stages appear to be the same from a broad
      comparative perspective, in that they begin with the eruption of the first molar
      and the achievement of the majority of adult brain size and end with sexual
      maturity, the detailed differences in the expression of these two stages, and how
      they relate to the preceding and following stages, suggest that a distinction
      should be maintained between them to avoid blurring subtle, but important,
      differences.

PMID- 22388877
TI  - Getting noticed. Middle childhood in cross-cultural perspective.
AB  - Although it is rarely named, the majority of societies in the ethnographic record
      demarcate a period between early childhood and adolescence. Prominent signs of
      demarcation are, for the first time, pronounced gender separation in fact and in
      role definition; increased freedom of movement for boys, while girls may be bound
      more tightly to their mothers; and heightened expectations for socially
      responsible behavior. But above all, middle childhood is about coming out of the
      shadows of community life and assuming a distinct, lifetime character. Naming and
      other rites of passage sometimes acknowledge this transition, but it is,
      reliably, marked by the assumption or assignment of specific chores or duties.
      Because the physiological changes at puberty are so much more dramatic, the
      transition from middle childhood is more often marked by a rite of passage than
      the entrance into this period. There is also an acknowledgment at the exit from
      middle childhood of near-adult levels of competence--as a herdsman or hunter or
      as gardener or infant-caretaker.

PMID- 22388880
TI  - Has the child welfare profession discovered nepotistic biases?
AB  - A major trend in foster care in developed countries over the past quarter century
      has been a shift toward placing children with "kin" rather than with unrelated
      foster parents. This change in practice is widely backed by legislation and is
      routinely justified as being in the best interests of the child. It is tempting
      to interpret this change as indicating that the child welfare profession has
      belatedly discovered that human social sentiments are nepotistic in their design,
      such that kin tend to be the most nurturant alloparents. Arguably, however, the
      change in practice has been driven by demographic, economic, and political forces
      rather than by discovery of its benefits. More and better research is needed
      before we can be sure that children have actually benefitted.

PMID- 22388878
TI  - Juvenile subsistence effort, activity levels, and growth patterns. Middle
      childhood among Pume foragers.
AB  - Attention has been given to cross-cultural differences in adolescent growth, but
      far less is known about developmental variability during juvenility (ages 3-10).
      Previous research among the Pume, a group of South American foragers, found that
      girls achieve a greater proportion of their adult stature during juvenility
      compared with normative growth expectations. To explain rapid juvenile growth, in
      this paper we consider girls' activity levels and energy expended in subsistence
      effort. Results show that Pume girls spend far less time in subsistence tasks in
      proportion to their body size compared with adults, and they have lower physical
      activity levels compared with many juveniles cross-culturally. Low activity
      levels help to explain where the extra energy comes from to support rapid growth
      in a challenging environment. We suggest that activity levels are important to
      account for the variation of resource and labor transfers in mediating energy
      availability.

PMID- 22388882
TI  - Feminization and altered gonadal gene expression profile by ethinylestradiol
      exposure to pejerrey, Odontesthes bonariensis, a South American teleost fish.
AB  - In pejerrey (Odontesthes bonariensis), ovarian differentiation has been
      associated with gonadal aromatase expression. It is also known that exposure of
      pejerrey larvae to estradiol (E(2)) produces all female populations. During the
      last few years, the presence of ethinylestradiol (EE(2)), a synthetic E(2)
      analogue, has been reported in water reservoirs of different parts of the world.
      In the present study, the effects of EE(2) were assessed on sex ratio bias and
      gene expression levels of gonadal aromatase (cyp19a1a), 11beta-hydroxysteroid
      dehydrogenase type 2 (hsd11b2), estrogens (eralpha, erbeta1), and androgen
      receptors (aralpha, arbeta). Pejerrey larvae were fed with commercial food
      containing EE(2) (0.1 and 1 ug/g) and E(2 ) (50 ug/g) as a positive control for
      six weeks after hatching. The gonadal histological analysis showed that 42 to 46%
      of the fish had clearly differentiated ovaries in both the EE(2) - and E(2) 
      treated groups, compared with 27% in the control group. Moreover, in the EE(2) -
      (1 ug/g) and E(2) -treated groups, no fish presented signs of testicular
      development compared with controls. In addition, expression of cyp19a1a and
      hsd11b2 was significantly up- and downregulated, respectively, by EE(2) and E(2)
      . The authors' results suggested that the feminization process driven by EE(2)
      depends on the positive balance of cyp19a1a in relation to hsd11b2. Thus, these
      genes can be used as early indicators of exposure to xenoestrogens in this
      species.

PMID- 22388879
TI  - Adrenarche and middle childhood.
AB  - Middle childhood, the period from 6 to 12 years of age, is defined socially by
      increasing autonomy and emotional regulation, somatically by the development of
      anatomical structures for subsistence, and endocrinologically by adrenarche, the
      adrenal production of dehydroepiandrosterone (DHEA). Here I suggest that DHEA
      plays a key role in the coordinated development of the brain and body beginning
      with middle childhood, via energetic allocation. I argue that with adrenarche,
      increasing levels of circulating DHEA act to down-regulate the release of glucose
      into circulation and hence limit the supply of glucose which is needed by the
      brain for synaptogenesis. Furthermore, I suggest the antioxidant properties of
      DHEA may be important in maintaining synaptic plasticity throughout middle
      childhood within slow-developing areas of the cortex, including the insula,
      thamalus, and anterior cingulate cortex. In addition, DHEA may play a role in the
      development of body odor as a reliable social signal of behavioral changes
      associated with middle childhood.

PMID- 22388883
TI  - [Special aspects of food allergy in children].
AB  - IgE-mediated allergic reactions to foods represent the earliest and most
      important manifestation of allergic diseases in childhood. Sensitization to foods
      may happen very early in life. Basic options for alimentary allergy prevention
      are breast-feeding of at least 4 months and in case  nursing is impossible, use
      of an alternative hypoallergenic formula. The most common food allergens in
      childhood are cow's milk, hen's egg, peanuts, tree nuts and wheat. The prevalence
      of food allergies in childhood is 2 to 6%. In up to 50% of infants and children
      with atopic eczema, food allergies play a role; vice versa 95% of children with
      an IgE-mediated food allergy have atopic eczema as an underlying disease.
      Diagnostic reliability in suspected allergic reactions to food is only achieved
      in most cases by performing controlled oral food challenges. The long-term
      prognosis is good for cow's milk and hen's egg allergy, while peanut and tree nut
      allergies often last life-long. The most important therapeutic option is a
      specific elimination diet; especially in infancy, a nutritionally adequate
      substitution diet has to be considered. Children who might inadvertently get into
      contact with their potentially life threatening food allergen, should be provided
      with an epinephrine autoinjector.

PMID- 22388885
TI  - Thrombocytopenia is more severe in patients with chronic hepatitis C than in
      patients with nonalcoholic fatty liver disease.

PMID- 22388884
TI  - Lansoprazole for secondary prevention of gastric or duodenal ulcers associated
      with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a
      prospective, multicenter, double-blind, randomized, double-dummy, active
      controlled trial.
AB  - BACKGROUND: Low-dose lansoprazole has not been intensively evaluated for its
      efficacy in the prevention of recurrent gastric or duodenal ulcers in patients
      receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain
      relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back
      pain. METHODS: This multi-center, prospective, double-blind, randomized, active
      controlled study involving 99 sites in Japan was designed to compare the efficacy
      of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a
      history of gastric or duodenal ulcers who required long-term NSAID therapy were
      randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice
      daily (n = 181) and followed up for 12 months or longer prospectively. RESULTS:
      The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361
      from the start of the study was calculated by the Kaplan-Meier method as 3.3,
      5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and
      36.9%, respectively, in the gefarnate group. The risk for ulcer development was
      significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in
      the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A
      long-term follow-up study showed an acceptable safety profile for low-dose
      lansoprazole therapy, with diarrhea as the most frequent adverse event.
      CONCLUSION: Lansoprazole was superior to gefarnate in reducing the risk of
      gastric or duodenal ulcer recurrence in patients with a definite history of
      gastric or duodenal ulcers who required long-term NSAID therapy.

PMID- 22388887
TI  - Properties of 7ND-CCL2 are modulated upon fusion to Fc.
AB  - 7ND, a truncated version of the chemokine MCP-1/CCL2 lacking amino acids 2-8, is
      a potent antagonist of CCR2. In contrast to CCL2, 7ND is an obligate monomer.
      Similar to other chemokines, the in vivo half-life of 7ND is very short and its
      use as an antagonist in disease models is thus limited. We therefore constructed
      a 7ND-Fc fusion protein to extend the half-life of 7ND and overcome its
      limitations as a potential therapeutic antagonist. When we tested the properties
      of the fusion molecule in vitro, we found to our surprise that 7ND-Fc, in
      contrast to 7ND, produced a distinct, albeit small, chemotactic response in THP-1
      cells, and a robust chemotactic response in L1.2 cells stably transfected with
      CCR2. To test whether this unexpected observation might be due to the bivalency
      of 7ND-Fc stemming from the dimeric nature of Fc fusions, we produced a
      heterodimeric Fc fusion which displays only one 7ND moiety, using a technology
      called strand exchange of engineered CH3 domains (SEED). The monovalent construct
      had properties equivalent to the parent 7ND. Furthermore, partial agonist
      activity appears to depend on receptor density as well as the signaling pathway
      examined. However, we were able to show that 7ND-Fc, but not 7ND alone, has
      antagonistic activity in experimental autoimmune encephalomyelitis, a murine
      model of multiple sclerosis.

PMID- 22388888
TI  - A size-exclusion permeability barrier and nucleoporins characterize a ciliary
      pore complex that regulates transport into cilia.
AB  - The cilium is a microtubule-based organelle that contains a unique complement of
      proteins for cell motility and signalling functions. Entry into the ciliary
      compartment is proposed to be regulated at the base of the cilium. Recent work
      demonstrated that components of the nuclear import machinery, including the Ran
      GTPase and importins, regulate ciliary entry. We hypothesized that the ciliary
      base contains a ciliary pore complex whose molecular nature and selective
      mechanism are similar to those of the nuclear pore complex. By microinjecting
      fluorescently labelled dextrans and recombinant proteins of various sizes, we
      characterize a size-dependent diffusion barrier for the entry of cytoplasmic
      molecules into primary cilia in mammalian cells. We demonstrate that nucleoporins
      localize to the base of primary and motile cilia and that microinjection of
      nucleoporin-function-blocking reagents blocks the ciliary entry of kinesin-2
      KIF17 motors. Together, this work demonstrates that the physical and molecular
      nature of the ciliary pore complex is similar to that of the nuclear pore
      complex, and further extends functional parallels between nuclear and ciliary
      import.

PMID- 22388889
TI  - CDK5 and MEKK1 mediate pro-apoptotic signalling following endoplasmic reticulum
      stress in an autosomal dominant retinitis pigmentosa model.
AB  - Chronic stress in the endoplasmic reticulum (ER) underlies many degenerative and
      metabolic diseases involving apoptosis of vital cells. A well-established example
      is autosomal dominant retinitis pigmentosa (ADRP), an age-related retinal
      degenerative disease caused by mutant rhodopsins. Similar mutant alleles of
      Drosophila Rhodopsin-1 also impose stress on the ER and cause age-related retinal
      degeneration in that organism. Well-characterized signalling responses to ER
      stress, referred to as the unfolded protein response (UPR), induce various ER
      quality control genes that can suppress such retinal degeneration. However, how
      cells activate cell death programs after chronic ER stress remains poorly
      understood. Here, we report the identification of a signalling pathway mediated
      by cdk5 and mekk1 required for ER-stress-induced apoptosis. Inactivation of these
      genes specifically suppressed apoptosis, without affecting other protective
      branches of the UPR. CDK5 phosphorylates MEKK1, and together, they activate the
      JNK pathway for apoptosis. Moreover, disruption of this pathway can delay the
      course of age-related retinal degeneration in a Drosophila model of ADRP. These
      findings establish a previously unrecognized branch of ER-stress response
      signalling involved in degenerative diseases.

PMID- 22388890
TI  - Homeostatic control of recombination is implemented progressively in mouse
      meiosis.
AB  - Humans suffer from high rates of fetal aneuploidy, often arising from the absence
      of meiotic crossover recombination between homologous chromosomes. Meiotic
      recombination is initiated by double-strand breaks (DSBs) generated by the SPO11
      transesterase. In yeast and worms, at least one buffering mechanism, crossover
      homeostasis, maintains crossover numbers despite variation in DSB numbers. We
      show here that mammals exhibit progressive homeostatic control of recombination.
      In wild-type mouse spermatocytes, focus numbers for early recombination proteins
      (RAD51, DMC1) were highly variable from cell to cell, whereas foci of the
      crossover marker MLH1 showed little variability. Furthermore, mice with greater
      or fewer copies of the Spo11 gene--with correspondingly greater or fewer numbers
      of early recombination foci--exhibited relatively invariant crossover numbers.
      Homeostatic control is enforced during at least two stages, after the formation
      of early recombination intermediates and later while these intermediates mature
      towards crossovers. Thus, variability within the mammalian meiotic program is
      robustly managed by homeostatic mechanisms to control crossover formation,
      probably to suppress aneuploidy. Meiotic recombination exemplifies how order can
      be progressively implemented in a self-organizing system despite natural cell-to
      cell disparities in the underlying biochemical processes.

PMID- 22388891
TI  - Fbxw7alpha- and GSK3-mediated degradation of p100 is a pro-survival mechanism in
      multiple myeloma.
AB  - Fbxw7alpha is a member of the F-box family of proteins, which function as the
      substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase
      complexes. Using differential purifications and mass spectrometry, we identified
      p100, an inhibitor of NF-kappaB signalling, as an interactor of Fbxw7alpha. p100
      is constitutively targeted in the nucleus for proteasomal degradation by
      Fbxw7alpha, which recognizes a conserved motif phosphorylated by GSK3. Efficient
      activation of non-canonical NF-kappaB signalling is dependent on the elimination
      of nuclear p100 through either degradation by Fbxw7alpha or exclusion by a newly
      identified nuclear export signal in the carboxy terminus of p100. Expression of a
      stable p100 mutant, expression of a constitutively nuclear p100 mutant,
      Fbxw7alpha silencing or inhibition of GSK3 in multiple myeloma cells with
      constitutive non-canonical NF-kappaB activity results in apoptosis both in cell
      systems and xenotransplant models. Thus, in multiple myeloma, Fbxw7alpha and GSK3
      function as pro-survival factors through the control of p100 degradation.

PMID- 22388893
TI  - [Italian Society of Nephrology 2011-2012: work in progress, accomplished, and
      planned - letter from president].

PMID- 22388892
TI  - Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB
      signalling.
AB  - Maintenance of adult tissues is carried out by stem cells and is sustained
      throughout life in a highly ordered manner. Homeostasis within the stem-cell
      compartment is governed by positive- and negative-feedback regulation of
      instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite
      for maintenance of the intestinal epithelium following injury and tumour
      formation. As ErbB-family ligands and receptors are highly expressed within the
      stem-cell niche, we hypothesize that strong endogenous regulators must control
      the pathway in the stem-cell compartment. Here we show that Lrig1, a negative
      feedback regulator of the ErbB receptor family, is highly expressed by intestinal
      stem cells and controls the size of the intestinal stem-cell niche by regulating
      the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has
      so far been attributed to a combination of Wnt and Notch activation and Bmpr
      inhibition. Our findings reveal ErbB activation as a strong inductive signal for
      stem-cell proliferation. This has implications for our understanding of ErbB
      signalling in tissue development and maintenance and the progression of malignant
      disease.

PMID- 22388894
TI  - [Diagnosis of acute renal injury by serum creatinine: negative perception vs
      evidence].

PMID- 22388895
TI  - [A circulating factor responsible for FSGS? suPAR!].

PMID- 22388896
TI  - [Black monday. Effect of interdialytic interval on survival].

PMID- 22388897
TI  - [A defense against the troll?].

PMID- 22388898
TI  - [The solution against inactivity in dialyzed patients: walk the dog. Gentle joke
      or opportunity to reflect on our changing world?].

PMID- 22388899
TI  - [Some like it hot].

PMID- 22388900
TI  - [Forefronts in nephrology: gems from the mine of researchers].

PMID- 22388901
TI  - [Regional citrate anticoagulation: towards a first-choice treatment].
AB  - Continuous renal replacement therapy (CRRT) is the most widely used technique for
      the treatment of severe acute kidney injury in the critically ill. The need for
      prolonged anticoagulation is the most important drawback of CRRT and clinically
      important bleeding significantly increases the risk of death. Therefore,
      alternative anticoagulation methods should be more widely adopted. Among the
      potential alternatives to systemic heparin anticoagulation, regional citrate
      anticoagulation (RCA) is the most promising. By reducing ionized calcium inside
      the extracorporeal circuit, citrate is able to block the coagulation cascade at
      different levels. Compared with unfractionated heparin, several studies reported
      better filter survival times and a marked reduction of transfusion rates with
      RCA. Despite the positive reports about the efficacy and safety of RCA, the use
      of this alternative method of anticoagulation appears to be relatively limited.
      Desirable future improvements in RCA should be focused on simplifying protocols,
      minimizing the need for calcium and magnesium supplementation, increasing the
      flexibility of buffer balance, and introducing customized dialysis systems able
      to deliver automated RCA. In particular, safe protocols with automated delivery
      of citrate and calcium can allow easy parameter settings that can be adapted to a
      wide range of clinical situations, facilitating the wider use of RCA in the
      coming years.

PMID- 22388902
TI  - [Citrate: an additional resource for anticoagulation in continuous replacement
      therapy].
AB  - Anticoagulation of the extracorporeal circuit, necessary for the correct
      management of renal replacement treatment in acute renal failure, is essential.
      There is a high risk of bleeding secondary to the presence of complex platelet
      and coagulation abnormalities, the effect of uremia, recent surgery or a state of
      sepsis. This requires careful evaluation of the type of anticoagulation to be
      used to prevent blood clotting of the circuit, maintain filter efficiency, and
      minimize the risk of bleeding. In critically ill patients with no risk of
      bleeding, heparin is still the anticoagulant treatment of choice. With an
      increased bleeding risk or in particular situations such as HIT-II, dermatan
      sulfate can be safely used as an alternative to dilution driven. A valid
      additional resource in case of a high risk of bleeding is citrate, the use of
      which - thanks to its effectiveness and ease of use - is becoming more
      widespread. Citrate is able to provide regional anticoagulation without any
      interference with the patient. This makes it increasingly feasible to continue
      replacement therapy, allowing a sufficient number of hours to obtain the correct
      dialysis dose in critically ill patients with acute renal failure.

PMID- 22388903
TI  - [Citrate: a different mental approach to extracorporeal circuit anticoagulation].
AB  - Citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT)
      in intensive care units (ICUs) is a practical application of a regional technique
      in which anticoagulation is virtually restrained to the extracorporeal circuit.
      This technique involves a different mental approach to anticoagulation, which
      gives RCA an advantage over systemic anticoagulation. The efficacy of
      anticoagulation depends on the level of citratemia reached in the circuit (from 2
      to 6 mmol/L) and the associated decrease in ionized calcium (from 0.5 to 0.1
      mmol/L). Compared with heparin in ICU patients in terms of efficacy and safety,
      citrate is able to maintain circuit patency for the same time, if not longer. It
      also reduces the risk of bleeding and the need for blood transfusions. Metabolic
      alterations during RCA such as metabolic alkalosis, hypocalcemia and
      hypernatremia are rare and of little clinical impact; their incidence is similar
      to those reported during CRRT with heparin. In patients at risk of citrate
      accumulation due to liver metabolism failure, the citrate load returning to the
      patient can be reduced by increasing the dialysis effluent volume. The popularity
      of RCA worldwide is neither high nor uniform. Apart from clinical indications,
      its diffusion is influenced by local and logistic conditions, the level of staff
      skill, and economic factors. However, thanks to the availability of dedicated
      monitors, disposable materials, and easy-to-learn operative protocols fitting
      patients' needs the use of RCA is increasing. For these reasons, RCA is expected
      to become the ruling anticoagulation approach during CRRT in ICUs.

PMID- 22388904
TI  - [Diuretic therapy in patients with congestive heart failure: an update].
AB  - Heart failure is one of the major causes of hospitalization in Italy and the
      Western world and is characterized by different pathophysiological conditions and
      multiple precipitating factors. The state of congestion, which is the main
      clinical presentation on admission, is treated in the majority of cases with
      diuretic therapy until hemodynamics are normalized and symptoms resolved.
      Treatment with loop diuretics, although widely used in the treatment of chronic
      heart failure, may result in diuretic resistance, electrolyte and volemic
      imbalance, neurohormonal activation, and worsening renal function. In this
      article the mechanisms of diuretic resistance and the strategies used to treat it
      and to optimize diuretic therapy of heart failure are discussed.

PMID- 22388905
TI  - [Novel immunological aspects of pediatric kidney transplantation].
AB  - Pediatric kidney transplantation has been a serious challenge from the outset.
      The main reason lies in the immune system of children, which presents significant
      differences in terms of lymphocyte subpopulation distribution and alloimmune
      response activation from the adult immune system. These differences are greatest
      between neonates and adults, while they decrease in a linear and age-dependent
      fashion. In the past, kidney transplantation in children was a courageous
      initiative, given the poorer outcomes compared with adult recipients. Today,
      thanks to advances in therapy protocols and a better knowledge of the pediatric
      immune system, graft survival in pediatric patients has significantly improved
      and transplantation is the standard of care for the treatment of chronic organ
      failure in children. Moreover, there is growing interest in the field of
      pediatric transplantation because of the recipients' peculiar infective risk
      profile, the underestimated cardiovascular risk, and the necessity to identify
      both new non-invasive diagnostic techniques and the characteristics that make the
      pediatric immune system so peculiar. Acquiring new knowledge in those fields may
      slow down the adoption of new therapies but, on the other hand, it may represent
      a starting point to provide pediatric allograft recipients with diagnostic and
      therapeutic advantages and ultimately achieve allograft tolerance.

PMID- 22388906
TI  - [Use of ECG-EC in the positioning of central venous catheters].
AB  - Central venous catheters (CVC) are widely used in clinical practice for the
      administration of chemotherapy, parental nutrition, hemodynamic monitoring, and
      hemodialysis. International guidelines have defined the right internal jugular
      vein as the preferred site of CVC insertion and underline that accurate
      positioning of the catheter tip is essential to maximize the blood flow and
      reduce long-term complications. Endocavitary electrocardiography (EC-ECG)
      improves the accuracy of catheter tip positioning without increasing the
      placement time by the recognition of typical P wave patterns during catheter
      insertion:the normally shaped P wave identifies the mid to upper superior vena
      cava, the widest P wave may be used to place the CVC tip at the superior vena
      cava-right atrium junction, and biphasic P waves identify the location of the
      right atrium. Because of its simplicity and safety, EC-ECG should always be
      considered during CVC placement, especially if other means of verifying correct
      CVC insertion are not available.

PMID- 22388907
TI  - [Plasma cell dyscrasias and renal damage].
AB  - Kidney damage caused by immunoglobulin free light chains in the setting of plasma
      cell dyscrasias is common and may involve all renal compartments, from the
      glomerulus to the tubulointerstitium, in a wide variety of histomorphological and
      clinical patterns. The knowledge of how free light chains can promote kidney
      injury is growing: they can cause functional changes, be processed and deposited,
      mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone
      of the free light chain is unique and its primary structure and post-translation
      modification can determine the type of renal disease. Measurement of serum free
      light chain concentrations and calculation of the serum kappa/lambda ratio,
      together with renal biopsy, represent essential diagnostic tools. An early and
      correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early
      initiation of disease-specific treatment strategies. The treatment of free light
      chain nephropathies is evolving and knowledge of the pathways that promote renal
      damage should lead to further therapeutic developments.

PMID- 22388908
TI  - [SIN census 2008: the management model].
AB  - This paper reports the analysis of the second part of the data obtained from the
      second SIN census and illustrates the management model of the Italian dialysis
      centers, highlighting its strengths but also its limits. The census was carried
      out between March and December 2008 with a webbased survey using fillable PDF
      forms. The survey was validated by comparing the data with those sent to the
      Italian Dialysis and Transplant Register (Registro Italiano di Dialisi e
      Trapianti, RIDT) and hence it refers to December 31, 2008, the date of the last
      RIDT report. Forty-two percent of dialysis centers, which altogether take care of
      50% of Italian dialysis patients, participated in the census. The participation
      percentage was very variable among Italian regions (from 5% to 100% of dialysis
      centers). By excluding the three regions with a participation rate below 10%, the
      survey reached a participation rate of 68% of all Italian dialysis centers and is
      therefore sufficient to give an estimate of the Italian dialysis situation.
      However, because of this variability it was not possible to compare regional
      situations, and the data were evaluated only by analyzing the ''complex'' and
      ''simple'' dialysis centers separately. The state of affairs of dialysis in Italy
      on the whole proved to be complicated. It is striking, for example, that 15% of
      the ''complex'' dialysis centers do not have their own hospital beds and some of
      them lack traceability programs. Noteworthy are also the increasing use of
      central venous catheters and the number of patients that need an ambulance to get
      to the dialysis center. Despite its limits due to the reduced participation in
      the census, this work offers a fair description of the state of affairs of
      dialysis in Italy, where there is certainly space for qualitative improvement.
      First of all, however, every effort should be made to implement and improve the
      use of the existing structures and to standardize protocols and behaviors in all
      Italian dialysis centers.

PMID- 22388909
TI  - [Ultrasound and color Doppler in nephrology. Physical and technical principles].
AB  - Sonography is an imaging technique that generates tomographic images using
      ultrasound. The sound constitutes mechanical energy transmitted in a medium by
      pressure waves. Sound waves with frequencies greater than 20 kHz are called
      ultrasounds. Diagnostic ultrasounds use frequencies from 1 to 20 MHz. Ultrasound
      equipment is composed of a scanner, an image monitor, and different transducers
      that transform acoustic energy into electrical signals and electrical energy into
      acoustic energy (piezoelectric effect). The spatial resolution defines the
      minimum distance between two reflectors or echogenic regions that can be imaged
      as separate reflectors. The spatial resolution is mainly determined by the array
      design (linear, curved and sectorial) and by the operative system of the
      transducer. Modern ultrasound machines are very sophisticated medical devices
      that often support many transducers, imaging modes and display devices. The scan
      converter memory is the device in which images are formed and then presented to
      the monitor and to the hard copy devices.

PMID- 22388910
TI  - [Severe recurrent intrahepatic cholestasis in systemic AL amyloidosis without
      obvious liver involvement: unexplained hepatic toxicity or a case of misdiagnosed
      liver amyloidosis?].
AB  - We report the case of a 50-year-old woman who was admitted to the hospital for
      acute abdominal pain with nephrotic proteinuria, rapidly progressive renal
      failure, and moderate anemia. Laboratory tests showed mild Bence Jones (lambda)
      proteinuria with negative serum immunofixation and a mild increase in lambda free
      light chains. A bone marrow biopsy and a fat tissue aspirate showed multiple
      myeloma and amyloidosis. Because of the end-stage renal disease, the patient
      began regular dialysis treatment and was started on bortezomib 1.3 mg/m2 plus
      dexamethasone 40 mg on days 1, 4, 8 and 11 of 21-day cycles. Ten days later she
      complained of a new episode of abdominal pain with jaundice. A CT scan and an MRI
      scan ruled out all secondary causes of cholangitis including cancer. Acute
      intrahepatic cholestasis due to amyloid deposition was then hypothesized. After 4
      well tolerated cycles of bortezomib and dexamethasone, blood tests showed a
      complete hematological response with full reversal of cholestasis. After three
      months, a new episode of abdominal pain occurred and this time the patient was
      operated on and found to have an intestinal volvulus. Because of the jaundice, a
      transjugular liver biopsy was performed showing no evidence of amyloid deposits.
      Two months later the patient died of septic shock. Although no autopsy was
      performed and the ultimate cause of the cholestasis could not be ascertained,
      amyloidosis remains the major culprit in this unfortunate case.

PMID- 22388911
TI  - [The civil liability of the physician].

PMID- 22388912
TI  - [Interview with Franco Tesio: nephrologist with a surgical bent or vice versa?
      The fascinating story of his venous catheter ''from bench to bedside''. Interview
      by Mario Timio].

PMID- 22388913
TI  - [Bicarbonate dialysis and ventilation].

PMID- 22388916
TI  - Engineering of contact resistance between transparent single-walled carbon
      nanotube films and a-Si:H single junction solar cells by gold nanodots.
AB  - The viability of single-walled carbon nanotubes (SWCNTs) as a transparent
      conducting electrode on a-Si:H based single junction solar cells was explored. A
      Schottky barrier formed at a SWCNT/a-Si:H interface was removed by introducing
      high work function gold nanodots at the SWCNT/a-Si:H interface. This allows
      comparable device performance from SWCNT-electrode-based a-Si:H solar cells to
      that obtained by using conventional transparent conducting oxides.

PMID- 22388917
TI  - Two novel positive cis-regulatory elements involved in green tissue-specific
      promoter activity in rice (Oryza sativa L ssp.).
AB  - In plant genetic engineering, using tissue-specific promoters to control the
      expression of target gene is an effective way to avoid potential negative effects
      of using constitutive promoter, such as metabolic burden and so on. However,
      until now, there are few tissue-specific promoters with strong and reliable
      expression that could be used in crop biotechnology application. In this study,
      based on microarray and RT-PCR data, we identified a rice green tissue-specific
      expression gene DX1 (LOC_Os12g33120). The expression pattern of DX1 gene promoter
      was examined by using the beta-glucuronidase (GUS) reporter gene and analyzed in
      transgenic rice plants in different tissues. Histochemical assays and
      quantitative analyses of GUS activity confirmed that P (DX1):GUS was highly
      expressed in green tissues. To identify the regulatory elements controlling the
      expression of the DX1 gene, a series of 5' and 3' deletions of DX1 promoter were
      fused to GUS gene and stably introduced into rice plants. In addition, gel
      mobility shift assays and site-directed mutagenesis studies were used, allowing
      for the identification of two novel tissue-specific cis-acting elements (GSE1 and
      GSE2) within P(DX1). GSE1 acted as a positive regulator in all green tissues
      (leaf, sheath, stem and panicle). Compared with GSE1, GSE2 acted as a positive
      regulator only in sheath and stem tissue, and had a weaker effect on gene
      expression. In addition, P(DX1):GUS was not expressed in anther and seed, this
      characteristic reduced the potential ecological risk and potential food safety
      issues. Taken together, our results strongly suggest that the identified
      promoter, P(DX1), and its cis regulatory elements, GSE1 and GSE2, are potentially
      useful in the field of rice transgenic breeding. KEY MESSAGE: We have isolated
      and characterized the rice green tissue-specific promoter P(DX1), and identified
      two novel positive cis-acting elements in P(DX1).

PMID- 22388919
TI  - [Genetically determined diseases. From clarification of the pathogenesis to
      consequences for therapy].

PMID- 22388918
TI  - Native-like aggregates of factor VIII are immunogenic in von Willebrand factor
      deficient and hemophilia a mice.
AB  - The administration of recombinant factor VIII (FVIII) is the first-line therapy
      for hemophilia A (HA), but 25%-35% of patients develop an inhibitory antibody
      response. In general, the presence of aggregates contributes to unwanted
      immunogenic responses against therapeutic proteins. FVIII has been shown to form
      both native-like and nonnative aggregates. Previously, we showed that nonnative
      aggregates of FVIII are less immunogenic than the native protein. Here, we
      investigated the effect of native-like aggregates of FVIII on immunogenicity in
      HA and von Willebrand factor knockout (vWF(-/-)) mice. Mice immunized with native
      like aggregates showed significantly higher inhibitory antibody titers than
      animals that received native FVIII. Following restimulation in vitro with native
      FVIII, the activation of CD4+ T-cells isolated from mice immunized with native
      like aggregates is approximately fourfold higher than mice immunized with the
      native protein. Furthermore, this is associated with increases in the secretion
      of proinflammatory cytokines IL-6 and IL-17 in the native-like aggregate
      treatment group. The results indicate that the native-like aggregates of FVIII
      are more immunogenic than native FVIII for both the B-cell and the T-cell
      responses.

PMID- 22388920
TI  - [Clinical and genetic aspects of hypertrophic and dilated cardiomyopathy].
AB  - Primary cardiomyopathies are frequent heart diseases with an estimated prevalence
      of 0.3-0.4% in the general population, significantly contributing to systolic
      heart failure and sudden cardiac death in the young. Molecular genetic studies
      have identified 49 different disease genes for hypertrophic and dilated
      cardiomyopathy, often involving proteins of the sarcomere, the cardiac Z-disc and
      the cytoskeleton. With the development of new, advanced technologies based on
      next-generation sequencing, it is now possible to efficiently screen all known
      disease genes in an individual patient. The clinical workup of cardiomyopathies
      should always include the investigation of the patient's family to account for
      the familial aggregation of cardiomyopathies and identify diseased as well as
      asymptomatic carriers of mutations. The detection of specific genotypes
      facilitates diagnostic classification and can improve risk stratification in
      affected patients.

PMID- 22388921
TI  - [Hereditary neuroendrocrine tumors. Multiple endocrine neoplasia type 1 and 2].
AB  - Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal-dominant hereditary
      disease characterized by the occurrence of tumors of the parathyroids, duodenum
      and/or pancreas, and anterior pituitary. The syndrome is caused by germline
      mutations of the MEN1 tumor suppressor gene. The identification of the causative
      mutations is of paramount importance for the long-term management of affected
      individuals and their relatives. Multiple endocrine neoplasia type 2 (MEN2) is
      less frequent than MEN1 and represents a cancer syndrome caused by autosomal
      dominant inherited mutations of the RET proto-oncogene, and displays a genotype
      phenotype correlation of remarkable clinical relevance. Major components of MEN-2
      comprise medullary thyroid carcinoma (MTC), pheochromocytoma, and primary
      hyperparathyroidism. Since 25-30% of patients with MTC display a hereditary
      background, genetic testing is indicated once MTC is diagnosed. Occurrence of MTC
      can be avoided by prophylactic thyroidectomy in early childhood in gene carriers.
      Early diagnosis and therapy of simultaneous pheochromocytoma avoids the
      development of complications caused by acute or chronic hypertension.

PMID- 22388922
TI  - [Benefits and risks of current pharmacotherapy in the treatment of type 2
      diabetes].
AB  - The development of new drugs for the treatment of type 2 diabetes (T2DM) and
      metabolic disorders is currently one of the most innovative areas of drug
      development. However, a considerable number of newly developed drugs have either
      not reached the market and were stopped late in development or have been
      withdrawn after initial approval soon after market authorization due to serious
      safety concerns. How can drug safety problems be anticipated and, even more
      important, how can adverse events definitely caused by a drug be differentiated
      from incidences of naturally occurring diseases? This review article will provide
      an update about the state of the art treatment of type 2 diabetes and reflect on
      the newest available study evidence on glitazones, incretin mimetics (GLP-1
      agonists and DPP-4 inhibitors), SGLT-2 inhibitors (gliflocines) and pan-PPAR
      agonists (glitazars). Furthermore, new and still experimental approaches for the
      treatment of T2DM, such as bardoxolone, salsalate and anakinra will be briefly
      reviewed.

PMID- 22388923
TI  - [Multiple hemangiomas, polyposis coli, endometrial and papillary thyroid cancer].
AB  - A 27-year-old female patient presented with multiple lipomas and cavernous
      hemangiomas of the skin, hemangioma of the parotid gland, polyps of the
      gastrointestinal tract and endometrial carcinoma. After 1 year the patient
      presented with papillary thyroid carcinoma and a diagnosis of Cowden syndrome
      (CS) was made. Genetic testing revealed a pathogenic PTEN gene mutation.
      Hereditary tumor syndromes, such as CS are underdiagnosed. Clinical management
      can be adjusted to the needs of CS patients only if an early diagnosis is made.
      In CS the risk for thyroid, breast and endometrial cancer is severely increased.

PMID- 22388924
TI  - Impairments in aromatase expression, reproductive behavior, and sperm quality of
      male fish exposed to 17beta-estradiol.
AB  - Growing evidence shows that environmental estrogen can reach levels that are high
      enough to exert adverse reproductive effects on wild fish populations. The
      authors report different parameters of male reproductive behavior, brain, and
      gonadal aromatase expression, as well as sperm quality in an internally
      fertilizing fish species (Jenynsia multidentata, Jenyns) exposed to
      environmentally relevant concentrations of 17beta-estradiol (E(2) ). Adult males
      were exposed to 0, 50, 100, and 250 ng/L E(2) over 28 d. The authors' findings
      demonstrate that E(2) exposure resulted in a very clear increase in brain
      aromatase transcript abundance at all assayed concentrations compared with
      control; however, no effects on gonadal aromatase expression were observed.
      Behavioral measures revealed increased sexual activity at 50 ng/L but not 100 or
      250 ng/L E(2) . In contrast to the molecular and behavioral responses, the
      condition factor, gonadosomatic index, and sperm quality were unaltered by E(2)
      exposure. The results from the present work suggest that E(2) affects some
      aspects of the reproductive biology of J. multidentata. These modifications in
      the reproductive biology caused by exposure to E(2) could potentially lead to
      long-term effects at population levels that may not always be immediately
      evident. To the best of the authors' knowledge, this is the first report on the
      combined effect of E(2) on aromatase expression, sexual behavior, and sperm
      parameters in fish.

PMID- 22388925
TI  - Aminohydroxyacetone synthons: versatile intermediates for the organocatalytic
      asymmetric aldol reaction.
AB  - A practical method for the synthesis of 1,3-aminohydroxyacetone synthons was
      developed, and their utility in the organocatalytic asymmetric aldol reaction was
      demonstrated in a short synthesis of aza-sugars.

PMID- 22388926
TI  - Perinatal dexamethasone-induced alterations in apoptosis within the hippocampus
      and paraventricular nucleus of the hypothalamus are influenced by age and sex.
AB  - Exposure to high levels of glucocorticoids (GCs) during development leads to long
      term changes in hypothalamic-pituitary-adrenal (HPA) axis regulation, although
      little is known about the neural mechanisms that underlie these alterations. In
      this study, we investigated the effects of late gestational (days 18-22) or
      postnatal (days 4-6) administration of the GC receptor agonist dexamethasone
      (DEX) on an apoptosis marker in two brain regions critical to HPA axis
      regulation, the hippocampus and the hypothalamic paraventricular nucleus (PVN).
      One day after the final DEX injection, male and female rats were sacrificed, and
      brains were processed for immunohistochemical detection of cleaved caspase-3, an
      apoptotic cell death indicator. DEX increased cleaved caspase-3 immunoreactivity
      in the CA1 hippocampal region of both sexes following prenatal but not postnatal
      treatment. Prenatal DEX also increased caspase-3 immunoreactivity in the CA3
      region, an elevation that tended to be greater in females. In contrast, postnatal
      DEX resulted in a much smaller, albeit significant, induction in CA3 caspase-3
      compared with prenatal treatment. Quantitative real-time PCR analysis revealed
      that prenatal but not postnatal DEX-induced hippocampal cleaved caspase-3
      correlated with elevated mRNA of the proapoptotic gene Bad. Few caspase-3-ir
      cells were identified within the PVN regardless of treatment age, although
      postnatal but not prenatal DEX increased this number. However, the region
      immediately surrounding the PVN (peri-PVN) showed significant increases in
      caspase-3-ir cells following pre- and postnatal DEX. Together these findings
      indicate that developmental GC exposure increases apoptosis in HPAaxis-associated
      brain regions in an age- and sex-dependent manner.

PMID- 22388928
TI  - Kinking and breakage of the Rusch Lasertube.

PMID- 22388927
TI  - Peptides induce persistent signaling from endosomes by a nutrient transceptor.
AB  - The yeast Gap1 transceptor mediates amino acid activation of the protein kinase A
      pathway and undergoes endocytic internalization following amino acid transport.
      We identified three specific gamma-glutamyl dipeptides that cause persistent
      cyclic AMP-independent activation of protein kinase A, prevent Gap1 vacuolar
      sorting and cause Gap1 accumulation in endosomes. To our knowledge, these are the
      first examples of persistent agonists of a transceptor. In yeast mutants blocked
      in multivesicular body sorting, L-citrulline mimicked persistent signaling,
      further supporting that the internalized Gap1 transceptor keeps signaling.
      Unexpectedly, these dipeptides were transported by Gap1 and not by the regular
      dipeptide transporters. Their uptake was unusually sensitive to external pH and
      caused transient intracellular acidification. High external pH, NHA1 deletion or
      V-ATPase inhibition overcame the vacuolar sorting defect. Hence, this work has
      identified specific dipeptides that cause enhanced proton influx through the Gap1
      symporter, resulting in its defective vacuolar sorting, and independently
      transform it into a persistently signaling transceptor.

PMID- 22388929
TI  - Perioperative management of a patient with thyroid hormone resistance who
      underwent total thyroidectomy for thyroid cancer.
AB  - Resistance to thyroid hormone (RTH) is a rare, predominantly inherited syndrome
      that involves impaired tissue responsiveness to thyroid hormones. We describe the
      perioperative management of a patient with RTH who underwent total thyroidectomy.
      Although surgery performed under general anesthesia was uneventful, after the
      surgery the patient developed difficult-to-treat hypocalcemia that lasted until
      postoperative day 4. Moreover, thyroid function even after discharge remained
      unstable despite replacement therapy. We suggest that the parathyroid and thyroid
      function of patients with RTH be followed very closely and that nociceptive
      stimulus of the surgery and postoperative pain be reduced as much as possible.

PMID- 22388931
TI  - Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year
      longitudinal study in community-dwelling older people.
AB  - Frailty is a multidimensional geriatric syndrome characterised by a state of
      increased vulnerability to disease. Its causes are unclear, limiting
      opportunities for intervention. Age-related changes to the immune-endocrine axis
      are implicated. This study investigated the associations between the immune
      endocrine axis and frailty as well as mortality 10 years later among men and
      women aged 65 to 70 years. We studied 254 participants of the Hertfordshire
      Ageing Study at baseline and 10-year follow-up. At baseline, they completed a
      health questionnaire and had collection of blood samples for immune-endocrine
      analysis. At follow-up, Fried frailty was characterised and mortality
      ascertained. Higher baseline levels of differential white cell counts (WCC),
      lower levels of dehydroepiandosterone sulphate (DHEAS) and higher cortisol:DHEAS
      ratio were all significantly associated with increased odds of frailty at 10-year
      follow-up. Baseline WCC and cortisol:DHEAS clearly discriminated between
      individuals who went on to be frail at follow-up. We present the first evidence
      that immune-endocrine biomarkers are associated with the likelihood of frailty as
      well as mortality over a 10-year period. This augments our understanding of the
      aetiology of frailty, and suggests that a screening programme at ages 60-70 years
      could help to identify individuals who are at high risk of becoming frail and who
      would benefit from early, targeted intervention, for example with DHEA
      supplementation or anti-inflammatory strategies. Progress towards the prevention
      of frailty would bring major health and socio-economic benefits at the individual
      and the population level.

PMID- 22388930
TI  - Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating
      unesterified alpha-linolenic acid by rat liver.
AB  - Docosahexaenoic acid (DHA, 22:6n-3), an n-3 polyunsaturated fatty acid (PUFA)
      found at high concentrations in brain and retina and critical to their function,
      can be obtained from fish products or be synthesized from circulating alpha
      linolenic acid (alpha-LNA, 18:3n-3) mainly in the liver. With aging, liver
      synthetic enzymes are reported reduced or unchanged in the rat. To test whether
      liver synthesis-secretion of DHA from alpha-LNA changes with age, we measured
      whole-body DHA conversion coefficients and rates in unanesthetized adult male
      Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA,
      20:5n-3)- and DHA-containing diet. Unesterified [U- (13) C]alpha-LNA bound to
      albumin was infused intravenously for 2 h, while [(13) C]-esterified n-3 PUFAs
      were measured in arterial plasma, as were unlabeled unesterified and esterified
      PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with
      age, but esterified n-3 PUFA concentrations did not change significantly.
      Calculated conversion coefficients were not changed significantly with age,
      whereas synthesis-secretion rates (product of conversion coefficient and
      unesterified plasma alpha-LNA concentration) of esterified DHA and n-3 DPA were
      reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas
      half-lives increased. The results suggest that hepatic capacity to synthesize DHA
      and other n-3 PUFAs from circulating alpha-LNA is maintained with age in the rat,
      but that reduced plasma alpha-LNA availability reduces net synthesis-secretion.
      As unesterified plasma DHA is the form that is incorporated preferentially into
      brain phospholipid, its reduced synthesis may be deleterious to brain function in
      aged rats.

PMID- 22388932
TI  - Regulation of parkin and PINK1 by neddylation.
AB  - Neddylation is a posttranslational modification that plays important roles in
      regulating protein structure and function by covalently conjugating NEDD8, an
      ubiquitin-like small molecule, to the substrate. Here, we report that Parkinson's
      disease (PD)-related parkin and PINK1 are NEDD8 conjugated. Neddylation of parkin
      and PINK1 results in increased E3 ligase activity of parkin and selective
      stabilization of the 55 kDa PINK1 fragment. Expression of dAPP-BP1, a NEDD8
      activation enzyme subunit, in Drosophila suppresses abnormalities induced by
      dPINK1 RNAi. PD neurotoxin MPP(+) inhibits neddylation of both parkin and PINK1.
      NEDD8 immunoreactivity is associated with Lewy bodies in midbrain dopaminergic
      neurons of PD patients. Together, these results suggest that parkin and PINK1 are
      regulated by neddylation and that impaired NEDD8 modification of these proteins
      likely contributes to PD pathogenesis.

PMID- 22388933
TI  - Rescue of severely affected dystrophin/utrophin-deficient mice through scAAV
      U7snRNA-mediated exon skipping.
AB  - Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by
      mutations in the dystrophin gene that result in the absence of functional
      protein. Antisense-mediated exon skipping is one of the most promising approaches
      for the treatment of DMD and recent clinical trials have demonstrated encouraging
      results. However, antisense oligonucleotide-mediated exon skipping for DMD still
      faces major hurdles such as extremely low efficacy in the cardiac muscle, poor
      cellular uptake and relatively rapid clearance from circulation, which means that
      repeated administrations are required to achieve some therapeutic efficacy. To
      overcome these limitations, we previously proposed the use of small nuclear RNAs
      (snRNAs), especially U7snRNA to shuttle the antisense sequences after
      vectorization into adeno-associated virus (AAV) vectors. In this study, we report
      for the first time the efficiency of the AAV-mediated exon skipping approach in
      the utrophin/dystrophin double-knockout (dKO) mouse which is a very severe and
      progressive mouse model of DMD. Following a single intravenous injection of
      scAAV9-U7ex23 in dKO mice, near-normal levels of dystrophin expression were
      restored in all muscles examined, including the heart. This resulted in a
      considerable improvement of their muscle function and dystrophic pathology as
      well as a remarkable extension of the dKO mice lifespan. These findings suggest
      great potential for AAV-U7 in systemic treatment of the DMD phenotype.

PMID- 22388934
TI  - BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through
      the activation of TGFbeta-TAK1-MAPK pathways in PAH.
AB  - Pulmonary arterial hypertension (PAH) is a cardiovascular disorder associated
      with enhanced proliferation and suppressed apoptosis of pulmonary arterial smooth
      muscle cells (PASMCs). Heterozygous mutations in the type II receptor for bone
      morphogenetic protein (BMPR2) underlie the majority of the inherited and familial
      forms of PAH. The transforming growth factor beta (TGFbeta) pathway is activated
      in both human and experimental models of PAH. However, how these factors exert
      pro-proliferative and anti-apoptotic responses in PAH remains unclear. Using
      mouse primary PASMCs derived from knock-in mice, we demonstrated that BMPR-II
      dysfunction promotes the activation of small mothers against decapentaplegia
      independent mitogen-activated protein kinase (MAPK) pathways via TGFbeta
      associated kinase 1 (TAK1), resulting in a pro-proliferative and anti-apoptotic
      response. Inhibition of the TAK1-MAPK axis rescues abnormal proliferation and
      apoptosis in these cells. In both hypoxia and monocrotaline-induced PAH rat
      models, which display reduced levels of bmpr2 transcripts, this study further
      indicates that the TGFbeta-MAPK axis is activated in lungs following elevation of
      both expression and phosphorylation of the TAK1 protein. In ex vivo cell-based
      assays, TAK1 inhibits BMP-responsive reporter activity and interacts with BMPR-II
      receptor. In the presence of pathogenic BMPR2 mutations observed in PAH patients,
      this interaction is greatly reduced. Taken together, these data suggest
      dysfunctional BMPR-II responsiveness intensifies TGFbeta-TAK1-MAPK signalling and
      thus alters the ratio of apoptosis to proliferation. This axis may be a potential
      therapeutic target in PAH.

PMID- 22388935
TI  - Efficacy of enzyme replacement therapy in an aggravated mouse model of
      metachromatic leukodystrophy declines with age.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a
      functional deficiency of arylsulfatase A (ASA). Previous studies in ASA-knockout
      mice suggested enzyme replacement therapy (ERT) to be a promising treatment
      option. The mild phenotype of ASA-knockout mice did, however, not allow to
      examine therapeutic responses of the severe neurological symptoms that dominate
      MLD. We, therefore, generated an aggravated MLD mouse model displaying
      progressive demyelination and reduced nerve conduction velocity (NCV) and treated
      it by weekly intravenous injections of 20 mg/kg recombinant human ASA for 16
      weeks. To analyze the stage-dependent therapeutic effects, ERT was initiated in a
      presymptomatic, early and progressed disease stage, at age 4, 8 and 12 months,
      respectively. Brain sulfatide storage, NCV and behavioral alterations were
      improved only in early, but not in late, treated mice showing a clear age
      dependent efficacy of treatment. Hematopoietic stem cell transplantation (HSCT)
      for late-onset variants is the only therapeutic option for MLD to date. ERT
      resembles a part of the HSCT rationale, which is based on ASA supply by donor
      cells. Beyond ERT, our results, therefore, corroborate the clinical observation
      that HSCT is only effective when performed in early stages of disease.

PMID- 22388936
TI  - Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) comprise a heterogeneous group of metabolic
      storage diseases that present with the accumulation of autofluorescent
      lipopigment, neurodegeneration and premature death. Nine genes have been thus far
      identified as the cause of different types of NCL, with ages at onset ranging
      from around birth to adult, although the underlying etiology of the disease still
      remains elusive. We present a family with typical NCL pathology in which we
      performed exome sequencing and identified a single homozygous mutation in ATP13A2
      that fully segregates with disease within the family. Mutations in ATP13A2 are a
      known cause of Kufor-Rakeb syndrome (KRS), a rare parkinsonian phenotype with
      juvenile onset. These data show that NCL and KRS may share etiological features
      and implicate the lysosomal pathway in Parkinson's disease.

PMID- 22388937
TI  - Alterations in serum electrolytes, antioxidative enzymes and haematological
      parameters of Labeo rohita on short-term exposure to sublethal dose of nitrite.
AB  - An experiment was conducted to study the effects of short-term exposure to
      sublethal levels of nitrite on electrolyte regulation, antioxidative enzymes and
      haematological parameters in Labeo rohita juveniles. The fishes were exposed to
      graded levels of nitrite (0-15 mg l(-1)) for different duration (0, 12, 24, 48
      and 96 h). The 96-h LC(50) value for L. rohita (avg. wt, 66.5 +/- 0.5 g) was
      found to be 11.28 mg l(-1). Activities of antioxidative enzymes (catalase and
      superoxide dismutase), acetylcholine esterase (AChE) and methaemoglobin
      reductase, serum electrolytes (sodium, potassium and chloride), haematological
      parameters and blood glucose level significantly varied (P < 0.05) in a dose
      dependent manner. With increasing nitrite concentration and exposure period, a
      progressive reduction in the total erythrocyte count and haemoglobin were
      observed. With increase in nitrite concentration, a significant (P < 0.05)
      increase in activities was evidenced in catalase and superoxide dismutase in
      liver as well as gill, methaemoglobin reductase in blood, while progressive
      decline in AChE activity in brain was recorded. The serum sodium and chloride
      content showed a progressive decline, while potassium showed an increasing trend
      upon increase in nitrite concentration. The serum K(+) and Cl(-) after 96-h
      exposure demonstrated a linear relationship (Y = 0.221x + 2.542, R (2) = 0.938, P
      < 0.01 and Y = -5.760x + 129.5, R (2) = 0.952, P < 0.01, respectively) with
      nitrite concentrations. This study revealed that nitrite exposure causes
      alteration in all measured tissue enzymes, serum electrolytes and haematological
      parameters.

PMID- 22388940
TI  - Hemofiltration circuit use beyond 72 hours in pediatric continuous renal
      replacement therapy.
AB  - INTRODUCTION: During continuous renal replacement therapy (CRRT), hemofiltration
      circuits ideally are changed after 72 h since tubing integrity and flow rates are
      not guaranteed after this time interval. This potential risk must be weighed
      against the risk of hypotension during elective circuit changes in the unstable
      patient. The aim of this study was to examine the safety of circuits used beyond
      72 h in pediatric CRRT. METHODS: A retrospective chart review of all patients who
      underwent CRRT at our institution from January 2003 to October 2005 was
      performed. Procedures were divided into standard (<=72 h) and extended (>72 h)
      circuit duration groups. Patients who had more than one CRRT procedure (n=13)
      were excluded from study. RESULTS: 71 CRRT procedures were performed for 71
      patients. A total of 254 circuits were used, of which 64 (25%) were used for >72
      h. For circuits >72 h, the mean duration of use was 5.5 days +/- 1.8 (range 4
      11). There were no differences between the groups in age (p=0.12), weight
      (p=0.48), diagnosis (p=0.21), CRRT indication (p=0.07), CRRT mode (p=0.37),
      anticoagulation (p=0.53), blood flow rate (p=0.06), replacement rate (p=0.50) or
      dialysate rate (p=0.89). There were no incidents of membrane or tubing rupture in
      either group. CONCLUSIONS: Use of hemofiltration circuits beyond 72 h may be safe
      in pediatric patients undergoing CRRT without increased risk of tubing rupture.
      Our data suggest a need to redefine the limits of prolonged circuit use in
      pediatric CRRT.

PMID- 22388939
TI  - Microcarrier-based expansion process for hMSCs with high vitality and
      undifferentiated characteristics.
AB  - For cell therapy, a high biomass of human mesenchymal stem cells (hMSCs) is
      required for clinical applications, such as in the form of encapsulated implants.
      An easy and reproducible microcarrier-based stirred tank reactor cultivation
      process for hMSCs in 1.68 L scale is described. To avoid medium changes, studies
      comparing high-glucose DMEM (DMEM-HG) with low-glucose EMEM were performed
      showing that high-glucose medium has positive effects on cell proliferation and
      that cell differentiability remains. Studies on the inoculation strategy and cell
      density, carrier concentration, volume, and stirrer speed were performed and
      resulted in a set of optimized parameters, inoculation strategy was found to be
      45 minutes of static state and 2 minutes of stirring repeated in 4 cycles. The
      inoculation density was chosen to be 7*103 cells/cm2, and the carrier
      concentration of glass surface carrier was 25 g/L. For the described reactor
      system, a stirrer speed of 120 rpm for the inoculation process and a daily
      increase of 10 rpm up to 160 rpm were found to be suitable. Process
      reproducibility was shown by 3 repeated cultivations at the determined set of
      parameters allowing high biomass values of up to 7*108 cells per batch. With DMEM
      HG, no limitation of glucose was found, and lactate and ammonia remained lower
      than critical inhibitory concentrations. Comparison of the static (T-flask) and
      dynamic cultures in the stirred tank reactor showed for both cases, that cells
      were of high vitality and both maintained differentiability. In both cases,
      encapsulation of the cells resulted in high bead vitality, a basic requirement
      for cell therapy application.

PMID- 22388941
TI  - Flow competition between hepatic arterial and portal venous flow during
      hypothermic machine perfusion preservation of porcine livers.
AB  - Hypothermic machine perfusion (HMP) is regarded as a better preservation method
      for donor livers than cold storage. During HMP, livers are perfused through the
      inlet blood vessels, namely the hepatic artery (HA) and the portal vein (PV). In
      previous HMP feasibility studies of porcine and human livers, we observed that
      the PV flow decreased while the HA flow increased. This flow competition restored
      either spontaneously or by lowering the HA pressure (PHA). Since this phenomenon
      had never been observed before and because it affects the HMP stability, it is
      essential to gain more insight into the determinants of flow competition. To this
      end, we investigated the influence of the HMP boundary conditions on liver flows
      during controlled experiments. This paper presents the flow effects induced by
      increasing PHA and by obstructing the outlet blood vessel, which is the vena cava
      inferior (VCI). Flow competition was evoked by increasing PHA to 55-70 mmHg, as
      well as by obstructing the VCI. Remarkably, a severe obstruction resulted in a
      repetitive and alternating tradeoff between the HA and PV flows. These phenomena
      could be related to intra-sinusoidal pressure alterations. Consequently, a higher
      PHA is most likely transmitted to the sinusoidal level. This increased sinusoidal
      pressure reduces the pressure drop between the PV and the sinusoids, leading to a
      decreased PV perfusion. Flow competition has not been encountered or evoked under
      physiological conditions and should be taken into account for the design of liver
      HMP protocols. Nevertheless, more research is necessary to determine the optimal
      parameters for stable HMP.

PMID- 22388942
TI  - Characterizing the impact of minor cannula design modification.
AB  - OBJECTIVE: Bench evaluation of the hydrodynamic behavior of venous cannulas is a
      valuable technique for the analysis of their performance during cardiopulmonary
      bypass (CPB). The aim of this study was to investigate the effect of the internal
      diameter of the extracorporeal connecting tube of venous cannulas on flow rate
      (Q), pressure drop (delta P), and cannula resistance (delta P/Q2) values, using a
      computer assisted test bench. METHODS: An in vitro circuit was set up with
      silicone tubing between the test cannula encased in a movable reservoir, and a
      static reservoir. The delta P, defined as the difference between the drainage
      pressure and the preload pressure, was measured using high-fidelity Millar
      pressure transducers. Q was measured using an ultrasonic flowmeter. Data display
      and data recording were controlled using virtual instruments in a stepwise
      fashion. RESULTS: The 27 F smartcanula(r) with a 9 mm connecting tube diameter
      showed 17% less resistance compared to that with an 8 mm connecting tube
      diameter. Q values were 7.22+/-0.1 and 7.81+/-0.04 L/min for cannulas with 8 mm
      and 9 mm connecting tube diameters, respectively. The delta P/Q2 ratio values
      were 72% lower for the Medtronic cannula with a 9 mm connecting tube diameter
      compared to that with an 8 mm connecting tube diameter. Q values for the
      Medtronic cannula were 3.94+/-0.23 and 6.58+/-0.04 L/min with 8 mm and 9 mm
      connecting tube diameters, respectively. The 27 F smartcanula(r) showed 13% more
      flow rate compared to the 28 F Medtronic cannula using the unpaired Student t
      test (p<0.0001). CONCLUSIONS: Our results demonstrated that Q was increased but
      delta P and delta P/Q2 values were significantly decreased when the connecting
      tube diameter was increased for venous cannulas. The connecting tube diameter
      significantly affected the resistance to liquid flow through the cannula.
      Smartcanulas(r) outperform Medtronic cannulas.

PMID- 22388943
TI  - Quercetin up-regulates LDL receptor expression in HepG2 cells.
AB  - Quercetin, an abundant flavonol found in fruits and vegetable, has been
      implicated in lowering the risk of cardiovascular disease that is often
      associated with high plasma levels of low density lipoprotein (LDL) cholesterol.
      Here we investigated whether quercetin could modulate the expression of LDL
      receptors (LDLR) in HepG2 cells and the possible underlying mechanisms to exert
      quercetin's effects. We found that quercetin was able to induce LDLR expression
      with at least a 75 u m concentration, which was accompanied by an increase in
      nuclear sterol regulatory element binding protein 2 (SREBP2). This effect was
      mediated by activation of c-jun-N-terminal kinase (JNK) and extracellular signal
      regulated kinase (ERK) signalling pathways as implicated by experiments using
      chemical inhibitors of each pathway. When cells were challenged with protein
      synthesis inhibitors in quercetin-activated LDLR transcription, LDL mRNA levels
      were not significantly affected by cycloheximide but puromycin abolished
      quercetin-induced LDLR transcription. Taken together, we conclude that quercetin
      can initiate LDLR transcription by enhancing SREBP2 processing, but new protein
      synthesis might be necessary to exert a maximum effect of quercetin in the up
      regulation of the LDLR gene. Our findings demonstrate that quercetin strongly up
      regulated LDLR gene expression, which might elicit hypolipidemic effects by
      increasing the clearance of circulating LDL cholesterol levels from the blood.

PMID- 22388944
TI  - Female mobility and postmarital kin access in a patrilocal society.
AB  - Across a wide variety of cultural settings, kin have been shown to play an
      important role in promoting women's reproductive success. Patrilocal postmarital
      residence is a potential hindrance to maintaining these support networks, raising
      the question: how do women preserve and foster relationships with their natal kin
      when propinquity is disrupted? Using census and interview data from the Himba, a
      group of semi-nomadic African pastoralists, I first show that although women have
      reduced kin propinquity after marriage, more than half of married women are
      visiting with their kin at a given time. Mobility recall data further show that
      married women travel more than unmarried women, and that women consistently
      return to stay with kin around the time of giving birth. Divorce and death of a
      spouse also trigger a return to living with kin, leading to a cumulative pattern
      of kin coresidence across the lifespan. These data suggest that patrilocality may
      be less of a constraint on female kin support than has been previously assumed.

PMID- 22388945
TI  - Interhousehold meat sharing among Mayangna and Miskito horticulturalists in
      Nicaragua.
AB  - Recent analyses of food sharing in small-scale societies indicate that reciprocal
      altruism maintains interhousehold food transfers, even among close kin. In this
      study, matrix-based regression methods are used to test the explanatory power of
      reciprocal altruism, kin selection, and tolerated scrounging. In a network of 35
      households in Nicaragua's Bosawas Reserve, the significant predictors of food
      sharing include kinship, interhousehold distance, and reciprocity. In particular,
      resources tend to flow from households with relatively more meat to closely
      related households with little, as predicted by kin selection. This
      generalization is especially true of household dyads with mother-offspring
      relationships, which suggests that studies of food sharing may benefit from
      distinctions between lineal and collateral kin. Overall, this analysis suggests
      that exchanges among kin are primarily associated with differences in need, not
      reciprocity. Finally, although large game is distributed widely, qualitative
      observations indicate that hunters typically do not relinquish control of the
      distribution in ways predicted by costly signaling theory.

PMID- 22388946
TI  - Life history of female preferences for male faces: a comparison of pubescent
      girls, nonpregnant and pregnant young women, and middle-aged women.
AB  - Although scientific interest in facial attractiveness has developed substantially
      in recent years, few studies have contributed to our understanding of the
      ontogeny of facial preferences. In this study, attractiveness of 30 male faces
      was evaluated by four female groups: girls at puberty, nonpregnant and pregnant
      young women, and middle-aged women. The main findings are as follows: (1)
      Preference for sexy-looking faces was strongest in young, nonpregnant women. (2)
      Biologically more mature girls displayed more adultlike preferences. (3) The
      intragroup consistency for postmenopausal women was relatively low. (4) In terms
      of the preference pattern, pregnant women were more similar to perimenopausal
      women than they were to their nonpregnant peers. (5) Preference for youthful
      appearance decreased with the age of the women. I argue that the life history of
      female preferences for male faces is, to a large extent, hormone-driven and
      underpinned by a set of evolutionary adaptations.

PMID- 22388947
TI  - Review of Thomas N. Headland, Janet D. Headland, and Ray T. Uehara's Agta
      Demographic Database: Chronicle of a Hunter-gatherer Community in Transition
      (Dallas: SIL International, 2011).

PMID- 22388948
TI  - Nanoscale mid-infrared imaging of phase separation in a drug-polymer blend.
AB  - The applicability of nanoscale mid-infrared (mid-IR) spectroscopy for the study
      of the micro- and nanostructure of pharmaceutical drug-polymer systems was
      explored. Felodipine-poly(acrylic acid) (PAA) blends were used as model systems.
      Standard atomic force microscopy evaluation as a function of drug-polymer
      composition suggested limited miscibility, in line with previous findings.
      Localized spectra on a 50:50 (w/w) felodipine-PAA dispersion revealed that the
      discrete submicrometer domains formed corresponded to an amorphous felodipine
      rich phase while the continuous phase tended to be rich in PAA. Further,
      spectroscopic imaging at selected wavenumbers, enabling discrimination between
      both constituents, confirmed this finding and made it possible to chemically
      image differences in composition between each phase with submicrometer
      resolution.

PMID- 22388949
TI  - Synthesis of Fe3O4 and Pt nanoparticles on reduced graphene oxide and their use
      as a recyclable catalyst.
AB  - A bifunctional Fe(3)O(4)-Pt/reduced graphene oxide (rGO) composite, i.e.
      Fe(3)O(4) nanoparticles (~4.8 nm in size) and Pt nanoparticles (~5 nm in size)
      loaded on a rGO surface, has been synthesized. It shows great catalytic
      performance for the reduction of methylene blue. Recycling of the composite can
      be achieved by simply applying an external magnetic field. In addition, the
      Fe(3)O(4)-Pt/rGO composite exhibits a higher catalytic activity and selectivity
      for aqueous-phase aerobic oxidation of benzyl alcohol than does the FeO(x)-Pt on
      carbon nanotubes (i.e. FeO(x)-Pt/CNT composite). Moreover, the approach for the
      synthesis of Fe(3)O(4)-Pt/rGO composite is simple, and can be widely employed to
      produce other rGO-based composites with special properties. Our work indicates
      that the rGO-based bifunctional composite has great potential for practical
      applications in various fields, such as catalytic reaction, electrochemical
      sensing, clean energy, etc.

PMID- 22388950
TI  - A novel ketone olefination via organozinc reagents in the presence of diphenyl
      phosphite.
AB  - Carbonyl compounds react with organozinc reagents in the presence of diphenyl
      phosphite to give the corresponding olefins. A variety of 1,3-dienes and
      unsaturated esters were obtained in moderate to excellent yields under mild
      conditions.

PMID- 22388951
TI  - Electrocardiographic findings and myocardial damage in acute myocarditis detected
      by cardiac magnetic resonance.
AB  - Delayed-contrast-enhancement (DCE) magnetic resonance imaging (MRI) can identify
      areas of myocardial damage in patients with acute myocarditis (AM). The aim of
      this study was to assess the electrocardiographic findings in AM diagnosed by DCE
      MRI. Eighty-one patients (72 men, 35 +/- 13 years) with AM were prospectively
      enrolled. All of them underwent MRI and 12-lead-ECG recordings. In the admission
      electrocardiogram (ECG 1), as well as in that obtained 48 h later (ECG 2), the
      following parameters were analyzed: rhythm, PR, QRS, and QTc-intervals,
      intraventricular conduction, abnormal Q waves, ST segment elevation, and T wave
      inversion. On admission, 77 patients (95%) were in sinus rhythm, while four
      patients (6%) manifested severe arrhythmias. No difference between ECG 1 and ECG
      2 was observed regarding abnormal Q waves, PR, QRS, and QTc-intervals.
      Electrocardiogram 1 was normal in 26 patients (32%, normal ECG group), and
      abnormal in 55 patients (68%, abnormal ECG group). ST elevation was found in 46
      patients (57%), inverted T wave in seven patients (9%) and left bundle branch
      block (LBBB) in two patients (3%). Areas of DCE suggesting AM were found in each
      patient. No relationship concerning the location of the involved region (s) was
      found between ECG (leads with ST/T abnormalities) and MRI (areas showing DCE).
      The ECG in AM can either be normal or reflect abnormalities including
      arrhythmias, LBBB, ST segment elevation, and T wave inversion. The location of
      myocardial involvement deduced on the basis of ECG leads showing ST/T changes is
      not in close relationship with the areas of ventricular damage detected by MRI.

PMID- 22388952
TI  - Enzymatic plasmonic engineering of Ag/Au bimetallic nanoshells and their use for
      sensitive optical glucose sensing.
AB  - Enzyme works for plasmonic nanostructure: an interesting enzyme-responsive hybrid
      Ag/Au-GOx bimetallic nanoshell (NS) system is reported, in which control over the
      enzyme reaction of glucose oxidase (GOx) can automatically fine-tune the
      morphology (from complete NS to porous NS) and optical properties of the hybrid
      nanostructure. The phenomenon is further exploited as a new platform for
      sensitive optical glucose sensing.

PMID- 22388956
TI  - Further evidence that interfacial water is the main "driving force" of protein
      dynamics: a neutron scattering study on perdeuterated C-phycocyanin.
AB  - The fundamental role of hydration water (also called interfacial water) is widely
      recognized in protein flexibility, especially in the existence of the so-called
      protein "dynamical transition" at around 220 K. In the present study, we take
      advantage of perdeuterated C-phycocyanin (CPC) and elastic incoherent neutron
      scattering (EINS) to distinguish between protein dynamics and interfacial water
      dynamics. Powders of hydrogenated (hCPC) and perdeuterated (dCPC) CPC protein
      have been hydrated, respectively, with D(2)O or H(2)O and measured by EINS to
      separately probe protein dynamics (hCPC/D(2)O) and water dynamics (dCPC/H(2)O) at
      different time- and length-scales. We find that "fast" (<20 ps) local mean-square
      displacements (MSD) of both protein and interfacial water coincide all along the
      temperature range, with the same dynamical transition temperature at ~220 K. On
      higher resolution (<400 ps), two different types of motions can be separated: (i)
      localized motions with the same amplitude for CPC and hydration water and two
      transitions at ~170 and ~240 K for both; (ii) large scale fluctuations exhibiting
      for both water molecules and CPC protein a single transition at ~240 K, with a
      significantly higher amplitude for the interfacial water than for CPC. Moreover,
      by comparing these motions with bulk water MSD measured under the same
      conditions, we show no coupling between bulk water dynamics and protein dynamics
      all along the temperature range. These results show that interfacial water is the
      main "driving force" governing both local and large scale motions in proteins.

PMID- 22388957
TI  - The role of chemokine CC ligand 20 in patients with liver cirrhosis and
      hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: To evaluate the role of chemokine CC ligand 20 (CCL20) as a
      biomarker for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Ninety
      patients in four groups were enrolled in this prospective cross-sectional study:
      30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C
      virus infection (group III), and 15 healthy blood donors as controls. Alpha
      fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were
      measured in all groups. RESULTS: Serum levels of CCL20 were significantly
      different among the study groups (F=230.979, p<0.001). The highest level was
      found in HCC patients (57.305 +/- 6.386 pg/mL) followed by patients with
      cirrhosis (45.999 +/- 5.165 pg/mL) compared with 22.781 +/- 5.986 pg/mL and
      18.585 +/- 3.554 pg/mL in asymptomatic patients with HCV infection and controls,
      respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559,
      p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size
      (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV
      infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive
      value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity.
      In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455,
      p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). CONCLUSION:
      CCL20 may be used for the detection of HCC in HCV-infected patients with
      comparable specificity and higher sensitivity than AFP.

PMID- 22388958
TI  - Active dendrites support efficient initiation of dendritic spikes in hippocampal
      CA3 pyramidal neurons.
AB  - CA3 pyramidal neurons are important for memory formation and pattern completion
      in the hippocampal network. It is generally thought that proximal synapses from
      the mossy fibers activate these neurons most efficiently, whereas distal inputs
      from the perforant path have a weaker modulatory influence. We used confocally
      targeted patch-clamp recording from dendrites and axons to map the activation of
      rat CA3 pyramidal neurons at the subcellular level. Our results reveal two
      distinct dendritic domains. In the proximal domain, action potentials initiated
      in the axon backpropagate actively with large amplitude and fast time course. In
      the distal domain, Na(+) channel-mediated dendritic spikes are efficiently
      initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites
      showed a high Na(+)-to-K(+) conductance density ratio, providing ideal conditions
      for active backpropagation and dendritic spike initiation. Dendritic spikes may
      enhance the computational power of CA3 pyramidal neurons in the hippocampal
      network.

PMID- 22388959
TI  - Mitochondrial CB1 receptors regulate neuronal energy metabolism.
AB  - The mammalian brain is one of the organs with the highest energy demands, and
      mitochondria are key determinants of its functions. Here we show that the type-1
      cannabinoid receptor (CB(1)) is present at the membranes of mouse neuronal
      mitochondria (mtCB(1)), where it directly controls cellular respiration and
      energy production. Through activation of mtCB(1) receptors, exogenous
      cannabinoids and in situ endocannabinoids decreased cyclic AMP concentration,
      protein kinase A activity, complex I enzymatic activity and respiration in
      neuronal mitochondria. In addition, intracellular CB(1) receptors and
      mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization
      induced suppression of inhibition in the hippocampus. Thus, mtCB(1) receptors
      directly modulate neuronal energy metabolism, revealing a new mechanism of action
      of G protein-coupled receptor signaling in the brain.

PMID- 22388960
TI  - The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.
AB  - Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as
      part of innate immunity. Unfortunately, ischemia can also induce this pathway and
      inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX
      function by compensating cellular loss of electrons with protons. Accordingly, we
      investigated whether NOX-mediated brain damage in stroke can be inhibited by
      suppression of Hv1. We found that mouse and human brain microglia, but not
      neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required
      for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice
      lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h
      after stroke. These results indicate that Hv1-dependent ROS production is
      responsible for a substantial fraction of brain damage at early time points after
      ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the
      treatment of ischemic stroke.

PMID- 22388961
TI  - Tonic signaling from O2 sensors sets neural circuit activity and behavioral
      state.
AB  - Tonic receptors convey stimulus duration and intensity and are implicated in
      homeostatic control. However, how tonic homeostatic signals are generated and how
      they reconfigure neural circuits and modify animal behavior is poorly understood.
      Here we show that Caenorhabditis elegans O(2)-sensing neurons are tonic receptors
      that continuously signal ambient [O(2)] to set the animal's behavioral state.
      Sustained signaling relied on a Ca(2+) relay involving L-type voltage-gated
      Ca(2+) channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors.
      Tonic activity evoked continuous neuropeptide release, which helps elicit the
      enduring behavioral state associated with high [O(2)]. Sustained O(2) receptor
      signaling was propagated to downstream neural circuits, including the hub
      interneuron RMG. O(2) receptors evoked similar locomotory states at particular
      O(2) concentrations, regardless of previous d[O(2)]/dt. However, a phasic
      component of the URX receptors' response to high d[O(2)]/dt, as well as tonic-to
      phasic transformations in downstream interneurons, enabled transient
      reorientation movements shaped by d[O(2)]/dt. Our results highlight how tonic
      homeostatic signals can generate both transient and enduring behavioral change.

PMID- 22388963
TI  - In silico modeling of UDP-glucuronosyltransferase 1A10 substrates using the
      VolSurf approach.
AB  - UDP-glucuronosyltransferase 1A10 (UGT1A10) catalyzes glucuronidation of a wide
      range of chemicals including many drugs. Here, we report the first in silico
      model quantifying the substrate selectivity and binding affinity (as K(m)) for
      UGT1A10. The training set for model construction comprises 32 structurally
      diverse compounds, which are known substrates for UGT1A10. The model was derived
      by applying the standard VolSurf method involving calculation of VolSurf
      descriptors and partial least square (PLS) analyses. The yielded PLS model with
      two components shows statistical significance in both fitting and internal
      predicting (r(2) = 0.827, q(2) = 0.774). The model predictability was further
      validated against a test set of 11 external compounds. The activity values for
      all test substrates were predicted within 1 log unit. Moreover, the model reveals
      an overlay of chemical features influencing the enzyme-substrate binding. Those
      include the size and shape, capacity factors, hydrophilic regions, hydrophobic
      regions, and polarizability. In conclusion, the VolSurf approach is successfully
      utilized to establish a predictive model for UGT1A10. The derived model should be
      an efficient tool for high-throughput prediction of UGT1A10 metabolism.

PMID- 22388962
TI  - The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK
      MAPK cascade.
AB  - The ability of neurons to undergo regenerative growth after injury is governed by
      cell-intrinsic and cell-extrinsic regeneration pathways. These pathways represent
      potential targets for therapies to enhance regeneration. However, the signaling
      pathways that orchestrate axon regeneration are not well understood. In
      Caenorhabditis elegans, the Jun N-terminal kinase (JNK) and p38 MAP kinase (MAPK)
      pathways are important for axon regeneration. We found that the C. elegans SVH-1
      growth factor and its receptor, SVH-2 tyrosine kinase, regulate axon
      regeneration. Loss of SVH-1-SVH-2 signaling resulted in a substantial defect in
      the ability of neurons to regenerate, whereas its activation improved
      regeneration. Furthermore, SVH-1-SVH-2 signaling was initiated extrinsically by a
      pair of sensory neurons and functioned upstream of the JNK-MAPK pathway. Thus,
      SVH-1-SVH-2 signaling via activation of the MAPK pathway acts to coordinate
      neuron regeneration response after axon injury.

PMID- 22388964
TI  - Validation of a motivation-based typology of angry aggression among antisocial
      youths in Norway.
AB  - This article describes the validation of the Angry Aggression Scales (AAS), the
      Behavior Inhibition System and the Behavior Activation System (BIS/BAS) scales,
      the reactive aggression and proactive power scales in relation to a Norwegian
      sample of 101 antisocial youths with conduct problems (64 boys, 37 girls, mean
      age 15 +/- 1.3 years) and 101 prosocial controls matched on age, gender,
      education, ethnicity, and school district. Maximum likelihood exploratory factor
      analyses with oblique rotation were performed on AAS, BIS/BAS, reactive
      aggression and proactive power scales as well as computation of Cronbach's alpha
      and McDonald's omega. Tests for normality and homogeneity of variance were
      acceptable. Factor analyses of AAS and the proactive/reactive aggression scales
      suggested a hierarchical structure comprising a single higher-order angry
      aggression (AA) factor and four and two lower-order factors, respectively.
      Moreover, results suggested one BIS factor and a single higher-order BAS factor
      with three lower-order factors related to drive, fun-seeking and reward
      responsiveness. To compare scores of antisocial youths with controls, t-tests on
      the mean scale scores were computed. Results confirmed that antisocial youths
      were different from controls on the above-mentioned scales. Consistent with the
      idea that anger is associated with approach motivation, AAS scores correlated
      with behavioral activation, but only explosive/reactive and vengeful/ruminative
      AA correlated with behavioral inhibition. Results generally validated the
      quadruple typology of aggression and violence proposed by Howard (2009).

PMID- 22388966
TI  - The artemisia L. Genus: a review of bioactive essential oils.
AB  - Numerous members of the Anthemideae tribe are important as cut flowers and
      ornamental crops, as well as being medicinal and aromatic plants, many of which
      produce essential oils used in folk and modern medicine and in the cosmetics and
      pharmaceutical industry. Essential oils generally have a broad spectrum of
      bioactivity, owing to the presence of several active ingredients that work
      through various modes of action. Due to their mode of extraction, mostly by
      distillation from aromatic plants, they contain a variety of volatile molecules
      such as terpenes, phenol-derived aromatic and aliphatic components. The large
      genus Artemisia L., from the tribe Anthemideae, comprises important medicinal
      plants which are currently the subject of phytochemical attention due to their
      biological and chemical diversity. Artemisia species, widespread throughout the
      world, are one of the most popular plants in Chinese traditional preparations and
      are frequently used for the treatment of diseases such as malaria, hepatitis,
      cancer, inflammation and infections by fungi, bacteria and viruses. Extensive
      studies of the chemical components of Artemisia have led to the identification of
      many compounds as well as essentials oils. This review summarizes some of the
      main reports on the chemistry and anti-infective activities of Artemisia. Li.
      essential oils from the data in the recent literature (2000-2011).

PMID- 22388965
TI  - Effects of different extraction methods and conditions on the phenolic
      composition of mate tea extracts.
AB  - A simple and rapid HPLC method for determination of chlorogenic acid (5-O
      caffeoylquinic acid) in mate tea extracts was developed and validated. The
      chromatography used isocratic elution with a mobile phase of aqueous 1.5% acetic
      acid-methanol (85:15, v/v). The flow rate was 0.8 mL/min and detection by UV at
      325 nm. The method showed good selectivity, accuracy, repeatability and
      robustness, with detection limit of 0.26 mg/L and recovery of 97.76%. The
      developed method was applied for the determination of chlorogenic acid in mate
      tea extracts obtained by ethanol extraction and liquid carbon dioxide extraction
      with ethanol as co-solvent. Different ethanol concentrations were used (40, 50
      and 60%, v/v) and liquid CO2 extraction was performed at different pressures (50
      and 100 bar) and constant temperature (27 +/- 1  degrees C). Significant
      influence of extraction methods, conditions and solvent polarity on chlorogenic
      acid content, antioxidant activity and total phenolic and flavonoid content of
      mate tea extracts was established. The most efficient extraction solvent was
      liquid CO2 with aqueous ethanol (40%) as co-solvent using an extraction pressure
      of 100 bar.

PMID- 22388967
TI  - Synthesis, spectral and solid state characterization of a new bioactive hydrazine
      bridged cyclic diphosphonium compound.
AB  - The facile preparation of a racemic hydrazine bridged diphosphonium compound
      possessing a ring system analogous to bicyclo[3.3.2]decane is reported. Although
      the reaction yield is low, the structure of the compound, which possesses an
      eight-membered ring, two phosphonium cationic centers, a biimino bridge,
      molecular chirality and two fused aromatic rings locked into roughly
      perpendicular planes is unusual. The compound displays substantial biological
      activity in the brine shrimp test and cleaves plasmid DNA.

PMID- 22388968
TI  - Anti-addition mechanism in the intramolecular hydroalkoxylation of alkenes
      catalyzed by PVP-stabilized nanogold.
AB  - (1R*,4S*,4aR*,9aS*,10S*)-10-Hydroxy-10-phenyl-1,4a,9a,10-tetrahydro-1,4
      methanoanthracen-9(4H)-one (1c) was prepared for the elucidation of the reaction
      mechanism of intramolecular hydroalkoxylation of alkenes catalyzed by gold
      nanoclusters stabilized by a hydrophilic polymer, poly(N-vinyl-2-pyrrolidone)
      (Au:PVP). It was found that the reaction proceeded via anti-addition of alcohol
      to the alkene assisted by p-activation of the gold clusters, which is the same
      mechanism as the hydroamination by toluenesulfonamides.

PMID- 22388969
TI  - New constituents from the rhizomes of Egyptian Iris germanica L.
AB  - Chemical investigation of the methanolic extract of the rhizomes of Iris
      germanica L. (Iridaceae) afforded two new compounds; irigenin S (7) and iriside A
      (12), together with ten known compounds: stigmasterol (1), a-irone (2), gamma
      irone (3), 3-hydroxy-5-methoxyacetophenone (4), irilone (5), irisolidone (6),
      irigenin (8), stigmasterol-3-O-beta-D-glucopyranoside (9), irilone 4'-O-beta-D
      glucopyranoside (10) and iridin (11). Their structures were established by UV,
      IR, 1D (1H and 13C) and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in
      addition to mass spectroscopic data and comparison with literature data. The
      methanolic extract was evaluated for its antimicrobial activity. Both the
      methanolic extract and the isolated flavonoids were tested for their anti
      inflammatory activity.

PMID- 22388970
TI  - Intra-cavitary ECG is an effective method for correct positioning the tip of
      tunneled Groshong catheters.
AB  - BACKGROUND: Intra-cavitary electrocardiography (ECG) is a well-known method for
      correct positioning of the tip of central venous catheters (CVC). A significant
      increase in the P wave, as registered by the intra-cavitary electrode, signals
      the entrance of the catheter into the right atrium. METHODS: In this prospective
      observational study, 155 consecutive oncologic patients were enrolled for
      cannulation of the right or left internal jugular vein for insertion of a
      tunneled Groshong catheter. In 150 patients the tip was positioned by means of
      intracavitary ECG. Five patients with atrial fibrillation (N=4) or pacemaker in
      place (N=1) were excluded from the study. As the P-wave amplitude began to
      increase, the catheter was secured in that position and the insertion depth was
      registered. RESULTS: Intra-cavitary ECG was always apt to detect the increase in
      the P wave. On the post-operative chest x-ray all Groshong catheters except two
      were in the correct position. CONCLUSIONS: The need for chest x-ray or
      fluoroscopy may be virtually eliminated by using the ECG technique.

PMID- 22388971
TI  - New spirostanol glycosides from Solanum nigrum and S. jasminoides.
AB  - A new characteristic steroidal glycoside possessing a hydroxyl group at C-23,
      inunigroside A (1), was isolated from the withered berries of Solanum nigrum L.
      On the basis of spectroscopic analysis, the structure of 1 was characterized as
      (5alpha,22S,23S,25R)-3beta,23-dihydroxyspirostane 3-O-beta-lycotetraoside. Next,
      a major steroidal sapogenol, (22R, 25S)-3beta,15alpha-dihydroxy-spirost-5-ene
      (3), was obtained from the acid hydrolysate of the methanolic extract of the
      aerial parts of Solanum jasminoides L. A new bisdesmoside, 3-O-beta-D
      glucopyranosyl-(1->4)-beta-D-glucopyranosyl-(1->4)-beta-D-glucopyranosyl
      (22R,25S)-3beta,15alpha-dihydroxyspirost-5-ene 15-O-alpha-L-rhamnopyranoside (4),
      named jasminoside A, was isolated from the methanolic extract of S. jasminoides.

PMID- 22388972
TI  - Vasorelaxant effect of FR900359 from Ardisia crenata on rat aortic artery.
AB  - A cyclic depsipeptide, FR900359, isolated from Ardisia crenata was evaluated for
      vasorelaxant effects on rat aortic arteries. FR900359 caused concentration
      dependent relaxation (1 nM-10 MUM) in phenylephrine-precontracted endothelium
      intact aortic rings, which was inhibited by addition of L-NMMA, a NOS inhibitor.
      In endothelium-denuded rings, the relaxant effect of low concentrations of
      FR900359 was diminished, but remained at high concentrations. In endothelium
      denuded rings, FR900359 at 0.1 MUM significantly attenuated high-K(+)-induced
      contractions and completely inhibited Ca(2+)-induced contractions. These results
      suggest that the vasorelaxant effect of FR900359 is mediated through the
      increased release of NO from endothelial cells at low concentrations, and can be
      attributed to inhibitory effects on voltage-dependent Ca(2+) channel- and
      receptor-operated Ca(2+) channel-dependent Ca(2+) influx at high concentrations.

PMID- 22388973
TI  - Pharmacological properties of guggulsterones, the major active components of gum
      guggul.
AB  - Oleo gum resin secreted by Commiphora mukul, also known as gum guggul, has been
      used widely as an ayurvedic drug. Commiphora mukul is a short thorny shrub that
      is native to the Indian subcontinent. Oleo gum resin extracted by incision of the
      bark is a very complex mixture of gum, minerals, essential oils, terpenes,
      sterols, ferrulates, flavanones and sterones. Its active constituents, the Z- and
      E-guggulsterones, have been demonstrated to exhibit their biological activities
      by binding to nuclear receptors and modulating the expression of proteins
      involved in carcinogenic activities. Guggulsterones have also been reported to
      regulate gene expression by exhibiting control over other molecular targets
      including transcription factors such as nuclear factor (NF)-kappaB, signal
      transducer and activator of transcription (STAT) and steroid receptors.
      Considerable scientific evidence indicates the use of gum guggul as a therapeutic
      agent in the treatment of inflammation, nervous disorders, hyperlipidaemia and
      associated cardiac disorders such as hypertension and ischaemia, skin disorders,
      cancer and urinary disorders. This review highlights the taxonomic details,
      phytochemical properties and pharmacological profile of gum guggul.

PMID- 22388974
TI  - Mental health research in the Arab world.
AB  - PURPOSE: To assess the progression of mental health research over four decades in
      the Arab world. METHODS: Publications on mental health in 21 Arab countries from
      1966 to 2006 were screened using PubMed and Psychinfo. Data were collected and
      analyzed for Arab authors and affiliations, publication year, topic and type of
      journal. RESULTS: In 40 years (1966-2005), the Arab world published 2,213
      articles on a vast variety of topics, most common being mood, anxiety and
      substance use disorders, and mostly in international journals. By the last
      decade, the total yearly publications increased about eightfold since the first
      two decades, and nearly doubled from the third one. The disparity of output was
      high across countries. The highest yearly output was from Egypt, Saudi Arabia,
      Kuwait and Lebanon. Per million population, the top four producing countries were
      Kuwait, Bahrain, Lebanon and United Arab Emirates. CONCLUSIONS: Over a decade,
      the Arab world produced approximately 17% of the global output of mental health
      publications/million population and was comparative to Latin American and
      Caribbean countries. There is a wide gap in comparison with the industrialized
      world, with a fertile ground for cross-cultural and genetic studies.

PMID- 22388976
TI  - Respirable dry powder formulation of bleomycin for developing a pulmonary
      fibrosis animal model.
AB  - The main purpose of the present study was to develop a respirable powder (RP)
      formulation of bleomycin (BLM) as a research tool for developing a pulmonary
      fibrosis animal model. The BLM-RP was prepared with a jet-milling system, the
      physicochemical properties of which were characterized focusing on morphology,
      stability, particle size distribution, and inhalation performance. Under an
      accelerated condition, the BLM-RP was superior to BLM solution in terms of its
      stability. Cascade impactor analyses demonstrated high inhalation performance
      with emitted dose and fine particle fraction of approximately 99% and 46%,
      respectively. Intratracheal administration of the BLM-RP (3 mg BLM/kg) in rats
      led to significant increases in collagen production and recruitment of
      inflammatory cells in lung by approximately 1.5- and 29-fold, respectively. The
      collagen overexpression was consistent with the results from picrosirius red
      staining of lung tissues in the rats treated with BLM-RP. Inhaled tranilast (TL;
      100 MUg/rat), an antifibrotic agent, could ameliorate inflammatory/fibrotic
      responses with reductions of recruited inflammatory cells and collagen content by
      32% and 59%, respectively, validating the pulmonary fibrosis animal model. From
      these findings, the BLM-RP with improved stability could be a beneficial research
      tool for developing a pulmonary fibrosis model in drug discovery for antifibrotic
      drug candidates.

PMID- 22388975
TI  - Epileptiform activity in the CA1 region of the hippocampus becomes refractory to
      attenuation by cannabinoids in part because of endogenous gamma-aminobutyric acid
      type B receptor activity.
AB  - The anticonvulsant properties of marijuana have been known for centuries. The
      recently characterized endogenous cannabinoid system thus represents a promising
      target for novel anticonvulsant agents; however, administration of exogenous
      cannabinoids has shown mixed results in both human epilepsy and animal models.
      The ability of cannabinoids to attenuate release of both excitatory and
      inhibitory neurotransmitters may explain the variable effects of cannabinoids in
      different models of epilepsy, but this has not been well explored. Using acute
      mouse brain slices, we monitored field potentials in the CA1 region of the
      hippocampus to characterize systematically the effects of the cannabinoid agonist
      WIN55212-2 (WIN) on evoked basal and epileptiform activity. WIN, acting
      presynaptically, significantly reduced the amplitude and slope of basal field
      excitatory postsynaptic potentials as well as stimulus-evoked epileptiform
      responses induced by omission of magnesium from the extracellular solution. In
      contrast, the combination of omission of magnesium plus elevation of potassium
      induced an epileptiform response that was refractory to attenuation by WIN. The
      effect of WIN in this model was partially restored by blocking gamma-aminobutyric
      acid type B (GABA(B) ), but not GABA(A) , receptors. Subtle differences in models
      of epileptiform activity can profoundly alter the efficacy of cannabinoids.
      Endogenous GABA(B) receptor activation played a role in the decreased cannabinoid
      sensitivity observed for epileptiform activity induced by omission of magnesium
      plus elevation of potassium. These results suggest that interplay between
      presynaptic G protein-coupled receptors with overlapping downstream targets may
      underlie the variable efficacy of cannabinoids in different models of epilepsy.

PMID- 22388977
TI  - Subcellular dynamics of multifunctional protein regulation: mechanisms of GAPDH
      intracellular translocation.
AB  - Multidimensional proteins such as glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) exhibit distinct activities unrelated to their originally identified
      functions. Apart from glycolysis, GAPDH participates in iron metabolism, membrane
      trafficking, histone biosynthesis, the maintenance of DNA integrity and receptor
      mediated cell signaling. Further, multifunctional proteins exhibit distinct
      changes in their subcellular localization reflecting their new activities. As
      such, GAPDH is not only a cytosolic protein but is localized in the membrane, the
      nucleus, polysomes, the ER and the Golgi. In addition, although the initial
      subcellular localizations of multifunctional proteins may be of significance,
      dynamic changes in intracellular distribution may occur as a consequence of those
      new activities. As such, regulatory mechanisms may exist through which cells
      control multifunctional protein expression as a function of their subcellular
      localization. The temporal sequence through which subcellular translocation and
      the acquisition of new GAPDH functions is considered as well as post
      translational modification as a basis for its intracellular transport.

PMID- 22388978
TI  - PCBs stimulate laccase production and activity in Pleurotus ostreatus thus
      promoting their removal.
AB  - Pleurotus ostreatus degrades polychlorinated biphenyls (PCBs) with an increase of
      laccase activity. Laccases are well known for their detoxifying activity. We
      show, using reverse transcription polymerase chain reaction and a biochemical
      assay, that reduction in PCBs (di, tri, tetra, and penta) levels are correlated
      with an increase in laccase activity. P. ostreatus cultures were obtained from 0
      to 30 days in the presence or absence of 7,100 mg/L PCBs (from transformer oil)
      and a surfactant. After each selected time cultures were withdrawn and remaining
      PCBs were determined, a maximal removal percentage of PCBs was obtained at 20
      (63.5 +/- 2.0) and 30 days (63.8 +/- 4.6) post-induction. Also, the activity of
      the enzyme was analyzed and it was found to increase at 10 (6.9-fold) and 20
      (6.77-fold) days post-induction in the presence of PCBs, as determined by its
      activity. Taken together, these data suggest that PCBs induce laccase expression
      and that laccase catalyzes PCBs removal.

PMID- 22388980
TI  - Facile synthesis and application of poly(ionic liquid)-bonded silica hybrid
      materials.
AB  - Facile methods were developed to prepare hybrid poly(ionic liquid)-bonded silica
      for a wide range of applications, particularly in analytical chemistry. The
      hybrid material obtained was evaluated by comparing its adsorption capacity with
      other conventional separation materials. In addition, the hybrid material has the
      potential for industrial scale production.

PMID- 22388979
TI  - Biodegradation of pyrazosulfuron-ethyl by Acinetobacter sp. CW17.
AB  - The pyrazosulfuron-ethyl-degrading bacterium, designated as CW17, was isolated
      from contaminated soil near the warehouse of the factory producing pyrazosulfuron
      ethyl in Changsha city, China. The strain CW17 was identified as Acinetobacter
      sp. based on analyses of 94 carbon source utilization or chemical sensitivity in
      Biolog microplates, conventional phenotypic characteristics, and 16S rRNA gene
      sequencing. When pyrazosulfuron-ethyl was provided as the sole carbon source, the
      effects of pyrazosulfuron-ethyl concentration, pH, and temperature on
      biodegradation were examined. The degradation rates of pyrazosulfuron-ethyl at
      initial concentrations of 5.0, 20.0, and 50.0 mg/L were 48.0%, 77.0%, and 32.6%,
      respectively, after inoculation for 7 days. The growth of the strain was
      inhibited at low pH buffers. The chemical degradation occurs much faster at low
      pH than at neutral and basic pH conditions. The degradation rate of
      pyrazosulfuron-ethyl at 30 degrees C was faster than those at 20 and 37 degrees C
      by CW17 strains. Two metabolites of degradation were analyzed by liquid
      chromatography-mass spectroscopy (LC/MS). Based on the identified products,
      strain CW17 seemed to be able to degrade pyrazosulfuron-ethyl by cleavage of the
      sulfonylurea bridge.

PMID- 22388984
TI  - Comment on "Dynamic factors in the reactions between the magic cluster Al13(-)
      and HCl/HI" by Q. H. Yuan, J. Li, and Z.-F. Liu, Phys. Chem. Chem. Phys., 2011,
      13, 9871: a wavefunction instability problem.
AB  - We have investigated the wavefunction instabilities in the reaction between a
      metal cluster Al(13)(-) and a simple molecule HI. This work shows that Hartree
      Fock instability problems are appreciably responsible for the reported
      discrepancy between density functional and coupled-cluster results.

PMID- 22388983
TI  - The influence of preoperative MRI findings on lumbar fusion clinical outcomes.
AB  - INTRODUCTION: Spinal fusion as a treatment for degenerative disc disease is
      controversial. Prior authors have identified various MRI findings as being pain
      generators, which might help guide patient selection for lumbar fusion
      procedures. These findings have included disc desiccation, disc contour, high
      intensity zone annular disruption, the presence of Modic endplate changes, and
      disc space collapse. The purpose of this study is to investigate which MRI
      findings in patients with degenerative disc disease predict clinical improvement
      with lumbar fusion. METHODS: A single-center surgical database of patients
      undergoing lumbar fusion was reviewed for patients whose indication for fusion
      surgery was primary disc pathology. We identified 51 patients (71 disc levels)
      who had completed 2-year prospectively collected outcomes questionnaires and had
      preoperative MRIs available for review. NRS (0-10) back and leg pain, Oswestry
      Disability Index (ODI) and SF-36 Physical Composite Summary scores were obtained
      preoperatively and at 1- and 2-year follow-up. MRIs were reviewed by three
      fellowship-trained spine surgeons who were asked to grade them for the following
      five characteristics: (a) disc desiccation, (b) disc contour, (c) presence of a
      high-intensity zone (HIZ) annular tear, (d) presence of Modic endplate changes
      and (e) disc height. Two-year outcome measures were compared to MRI findings to
      identify which findings correlated with improvement in outcome scores. RESULTS:
      Statistically significant improvements were noted in back pain, leg pain, SF-36
      PCS and ODI in the group overall. Disc desiccation, disc contour, presence of an
      HIZ lesion, and the presence of Modic endplate changes did not correlate with 2
      year outcomes. Disc height was correlated with 2-year change in outcome measures.
      Discs with preoperative height less than 5 mm demonstrated a 23.4 point ODI
      improvement compared to 9.2 points for discs >7 mm. Similarly, SF-36 PCS improved
      9.5 points in discs <5 mm compared to 0.7 in discs greater than 7 mm. Discs
      between 5 and 7 mm demonstrated intermediate levels of improvement. CONCLUSIONS:
      Several commonly utilized MRI criteria proposed as indications for lumbar fusion
      do not seem to correlate with 2-year improvement in clinical outcomes. Discs
      which are narrowed and collapsed, preoperatively, demonstrate better improvement
      at 2 years postoperatively as compared to discs which have maintained disc
      height. Significant disc space collapse may represent a subset of "degenerative
      disc disease" which responds more favorably to treatment with fusion.

PMID- 22388985
TI  - Elevation of cartilage AGEs does not accelerate initiation of canine experimental
      osteoarthritis upon mild surgical damage.
AB  - Osteoarthritis is a highly prevalent disease, age being the main risk factor. The
      age-related accumulation of advanced-glycation-endproducts (AGEs) adversely
      affects the mechanical and biochemical properties of cartilage. The hypothesis
      that accumulation of cartilage AGEs in combination with surgically induced damage
      predisposes to the development of osteoarthritis was tested in vivo in a canine
      model. To artificially increase cartilage AGEs, right knee joints of eight dogs
      were repeatedly injected with ribose/threose (AGEd-joints). Left joints with
      vehicle alone served as control. Subsequently, minimal surgically applied
      cartilage damage was induced and loading restrained as much as possible. Thirty
      weeks after surgery, joint tissues of all dogs were analyzed for biochemical and
      histological features of OA. Cartilage pentosidine levels were ~5-fold enhanced
      (p = 0.001 vs. control-joints). On average, no statistically significant
      differences in joint degeneration were found between AGEd and control-joints.
      Enhanced cartilage pentosidine levels did correlate with less cartilage
      proteoglycan release (R = -0.762 and R = -0.810 for total and newly-formed
      proteoglycans, respectively; p = 0.028 and 0.015 for both). The current data
      support the diminished cartilage turnover, but only a tendency towards enhanced
      cartilage damage in AGEd articular cartilage was observed. As such, elevated AGEs
      do not unambiguously accelerate the development of early canine OA upon minimal
      surgical damage.

PMID- 22388986
TI  - Identification and regulation of a stage-specific stem cell niche enriched by
      Nanog-positive spermatogonial stem cells in the mouse testis.
AB  - The ability of spermatogonial stem cells to acquire embryonic stem cell (ESC)
      properties in vitro has recently been of great interest. However, studies focused
      on the in vivo regulation of testicular stem cells have been hampered because the
      exact anatomical location of these cells is unknown. Moreover, no specialized
      stem cell niche substructure has been identified in the mammalian testis thus
      far. It has also been unclear whether the adult mammalian testis houses
      pluripotent stem cells or whether pluripotency can be induced only in vitro.
      Here, we demonstrate, for the first time, the existence of a Nanog-positive
      spermatogonial stem cell subpopulation located in stage XII of the mouse
      seminiferous epithelial cycle. The efficiency of the cells from seminiferous
      tubules with respect to prolonged pluripotent gene expression was correlated
      directly with stage-specific expression levels of Nanog and Oct4, demonstrating
      the previously unknown stage-specific regulation of undifferentiated
      spermatogonia (SPG). Testicular Nanog expression marked a radioresistant
      spermatogonial subpopulation, supporting its stem cell nature. Furthermore, we
      demonstrated that p21 acts as an upstream regulator of Nanog in SPG and mouse
      ESCs, and our results demonstrate that promyelocytic leukemia zinc finger is a
      specific marker of progenitor SPG. Additionally, we describe a novel method to
      cultivate Nanog-positive SPG in vitro. This study demonstrates the existence and
      location of a previously unknown stage-specific spermatogonial stem cell niche
      and reports the regulation of radioresistant spermatogonial stem cells.

PMID- 22388987
TI  - Historical process lead to false genetic signal of current connectivity among
      populations.
AB  - Identification of the effects of historical processes on spatial genetic
      variation is of major importance in landscape genetics, especially in recent
      systems where the signal of recent isolation is often hardly perceptible. The
      goal of this study was to assess how differences in colonization patterns could
      influence spatial genetic variation using two centrarchidae species, the
      pumpkinseed sunfish (Lepomis gibbosus) and the rock bass (Ambloplites rupestris),
      from two adjacent drainage systems. The striking difference between the spatial
      genetic variations of the two species suggests completely opposite patterns of
      colonization. Rock bass colonized the drainage system from a downstream source,
      which resulted in a loss of diversity in upstream populations and a strong
      differentiation between drainage systems. In contrast, the reduction of genetic
      diversity and increase of differentiation toward downstream populations that were
      observed among sunfish populations suggest colonization from upstream to
      downstream. The colonization pattern observed in sunfish, which result in low
      differentiation between upstream most sites of the two drainages, leads to a
      false genetic signal of current inter-drainage gene flow. The present study
      demonstrates through empirical evidence that colonization patterns may impede the
      capacity to estimate current connectivity.

PMID- 22388988
TI  - Low-cost high-performance zinc antimonide thin films for thermoelectric
      applications.
AB  - Zinc antimonide thin films with high thermoelectric performance are produced by a
      simple sputtering method. The phase-pure Zn(4)Sb(3) and ZnSb thin films fulfill
      the key requirements for commercial TE power generation: cheap elements, cheap
      fabrication method, high performance and thermal stability. In addition, two
      completely new meta-stable crystalline phases of zinc antimonide have been
      discovered.

PMID- 22388989
TI  - Phorbol ester or epidermal growth-factor-induced MUC5AC mucin gene expression and
      production from airway epithelial cells are inhibited by apigenin and wogonin.
AB  - In this study, we investigated whether apigenin and wogonin affect MUC5AC mucin
      production and gene expression induced by phorbol ester (phorbol 12-myristate 13
      acetate, PMA) or epidermal growth factor (EGF) from human airway epithelial
      cells. Confluent NCI-H292 cells were pretreated with each agent for 30 min and
      then stimulated with PMA or EGF for 24 h, respectively. MUC5AC mucin gene
      expression and mucin protein production were measured by reverse transcription
      polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).
      The results were as follows: (i) apigenin and wogonin were found to inhibit the
      production of MUC5AC mucin protein induced by PMA or EGF; (ii) both compounds
      also inhibited the expression of MUC5AC mucin gene induced by PMA or EGF. These
      results suggest that apigenin and wogonin can inhibit mucin gene expression and
      production of mucin protein, by directly acting on airway epithelial cells.

PMID- 22388990
TI  - Hydrolysis of fungal and plant cell walls by enzymatic complexes from cultures of
      Fusarium isolates with different aggressiveness to rye (Secale cereale).
AB  - The efficiency of hydrolysis of fungal (Fusarium spp.) cell wall and rye root
      cell wall by crude enzymatic complexes from (42-day-old) cultures of three F.
      culmorum isolates, a plant growth-promoting rhizosphere isolate (PGPF) DEMFc2, a
      deleterious rhizosphere isolate (DRMO) DEMFc5, and a pathogenic isolate DEMFc37,
      as well as two other, pathogenic isolates belonging to F. oxysporum and F.
      graminearum species was studied. In the enzymatic complexes originating from the
      Fusarium spp. cultures, the activities of the following cell wall-degrading
      enzymes were identified: glucanases, chitinases, xylanases, endocellulases,
      exocellulases, pectinases, and polygalacturonases. The preparation originating
      from a culture of the PGPF isolate was the least efficient in plant cell wall
      (PCW) hydrolysis. There were no significant differences in the efficiency of PCW
      hydrolysis between preparations from cultures of the DRMO and the pathogenic
      isolates. PGPF was the most efficient in liberating reducing sugars and N
      acetylglucosamine (GlcNAc) from fungal cell walls (FCW). Xylanase activities of
      the enzymatic complexes were strongly positively (R > +0.9) correlated with their
      efficiency in hydrolyzing PCW, whereas chitinase activities were correlated with
      the efficiency in FCW hydrolysis.

PMID- 22388991
TI  - [Robot technology in the Italian Health-CARE system: cost-efficacy economic
      analysis].
AB  - BACKGROUND: Robotic technology is used in multiple fields of surgery, especially
      radical prostatectomy in patients with prostate cancer. The purpose of this study
      was to evaluate the introduction of robotic technology in the Italian Public
      Heath-care context, from the perspective of the Health Technology Assessment
      (HTA). An economic analysis that compares the costs and effectiveness of the
      method was developed. Data were compared with those of the most important
      international literature, analyzing structural and organizational problems
      related to the method. MATERIALS AND METHODS: A systematic review of literature
      on tertiary literature (Health Technology Assessment reports) and secondary
      (systematic reviews) published since 2002 was conducted. The review was also
      conducted on more recent primary literature regarding the clinical effectiveness
      and the economic analysis in the fields of surgery where Da Vinci robot is most
      promising. RESULTS: 18 studies were selected out of a total of 65 evaluated. The
      "Break-Even Point" (BEP) is the minimum number of cases needed to be treated in
      order to achieve a balance between costs and revenues, below which the system is
      losing money. It was calculated that the total fixed costs are ? 378,000 and
      variable costs are ? 3,810 per surgery. Considering that the current value of DRG
      (Diagnosis-Related Group) refunded by the public Health-care system is actually ?
      4,553, the BEP would be achieved performing 508 surgeries, so that the robotic
      technology does not generate neither profit nor loss. CONCLUSIONS: It is not
      possible to demonstrate the superiority of robotic surgery in terms of efficacy.
      The robotic surgery is safe and effective only if performed by surgical teams
      with relevant experience. Considering the reported case of an Italian University
      Hospital with public Health-care system refund, the BEP target of 508 radical
      prostatectomies could be achieved after a few years. The use of the robot in
      multiple fields on one hand shortens recovery time costs, but on the other hand
      increases costs due to organizational issues. The value of the DRG refund does
      not appear adequate to new robotic technology.

PMID- 22388992
TI  - Incidental prostatic stromal tumor of uncertain malignant potential (STUMP):
      histopathological and immunohistochemical findings.
AB  - Stromal prostate tumors are rare neoplastic proliferative lesions that have been
      classified into prostatic stromal tumor of uncertain malignant potential (STUMP)
      and prostatic stromal sarcoma (SS) based on these criteria: stromal cellularity,
      presence of mitotic figures, necrosis, and stromal overgrowth. A prostatic
      stromal tumor of uncertain malignant potential (STUMP) is a non-epithelial,
      mesenchymal spindle-cell tumor that can be classified as a specialized stromal
      tumor of the prostate. STUMPs have the capability to diffusely infiltrate the
      prostate gland and extend into adjacent tissues. Furthermore, they often recur
      and this is why they are considered as neoplastic entities. STUMPs usually tend
      to be not aggressive, but occasional cases have been reported with an extension
      into adjacent tissues. A few cases develop a sarcomatous dedifferentiation.  A 67
      year-old male referred to the Department of Urology, Sapienza Rome University,
      with acute urinary retention (AUR) and bladder overdistention. Digital rectal
      examination (DRE) showed the presence of a severe prostatic hyperplasia and a
      transvesical prostatic adenomectomy (TVPA) was performed. The pathological
      evaluation performed at the Department of Pathology, Sapienza Rome University,
      revealed an incidental diagnosis of prostatic STUMP. The patient's follow-up is
      made every year with transrectal ultrasonography and nuclear magnetic resonance
      with spectroscopy, and every two years with a transperineal prostate biopsy to
      exclude a progression to a stromal sarcoma. After 5 years of follow-up the STUMP
      is still detectable but there is no sign of sarcoma. As a result of its relative
      rarity and lack of long-term follow-up, the prognosis of STUMP is unclear.
      Therapy varies from a wait-and-see approach to a radical retropubic
      prostatectomy.

PMID- 22388993
TI  - Advancement in the research on vascular endothelial growth inhibitor (VEGI).
AB  - Vascular endothelial growth inhibitor (VEGI), also known as tumor necrosis factor
      superfamily member 15 or TNF ligand-related molecule 1, is identified as one kind
      of antiangiogenic cytokine that belongs to the tumor necrosis factor superfamily.
      VEGI includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. VEGI can activate
      multiple signaling pathways including nuclear factor-kappaB, c-Jun N-terminal
      kinase, and p38 mitogen-activated protein kinase. Moreover, it suppresses
      endothelial cell proliferation, angiopoiesis, and tumor growth. Genetic
      engineering techniques have been used to produce recombinant human vascular
      endothelial growth inhibitor, and great progress has been made in its application
      for curing cancer. VEGI could serve as a potential target in the development of
      angiogenesis-based cancer therapy, and this paper briefly summarizes the progress
      of the research on VEGI.

PMID- 22388994
TI  - Provisional diagnostic criteria for polymyalgia rheumatica: moving beyond
      clinical intuition?

PMID- 22388995
TI  - Ultrasound for enthesitis: handle with care!

PMID- 22388996
TI  - 2012 provisional classification criteria for polymyalgia rheumatica: a European
      League Against Rheumatism/American College of Rheumatology collaborative
      initiative.
AB  - The objective of this study was to develop EULAR/ACR classification criteria for
      polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month
      prospective cohort study of 125 patients with new onset PMR and 169 non-PMR
      comparison subjects with conditions mimicking PMR. A scoring algorithm was
      developed based on morning stiffness >45 minutes (2 points), hip pain/limited
      range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of
      peripheral joint pain (1 point). A score >=4 had 68% sensitivity and 78%
      specificity for discriminating all comparison subjects from PMR. The specificity
      was higher (88%) for discriminating shoulder conditions from PMR and lower (65%)
      for discriminating RA from PMR. Adding ultrasound, a score >=5 had increased
      sensitivity to 66% and specificity to 81%. According to these provisional
      classification criteria, patients >=50 years old presenting with bilateral
      shoulder pain, not better explained by an alternative pathology, can be
      classified as having PMR in the presence of morning stiffness>45 minutes,
      elevated CRP and/or ESR and new hip pain. These criteria are not meant for
      diagnostic purposes.

PMID- 22388997
TI  - Inflammation assessment in patients with arthritis using a novel in vivo
      fluorescence optical imaging technology.
AB  - BACKGROUND: Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI)
      is an established technology for imaging of inflammation in animal models. In
      experimental models of arthritis, FOI findings corresponded to histologically
      proven synovitis. This is the first comparative study of FOI with other imaging
      modalities in humans with arthritis. METHODS: 252 FOI examinations (Xiralite
      system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight,
      sequence of 360 images, one image per second) were compared with clinical
      examination (CE), ultrasonography (US) and MRI of patients with arthritis of the
      hands. RESULTS: In an FOI sequence, three phases could be distinguished (P1-P3).
      With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%,
      while the specificity of phase 1 was 94%. FOI had agreement rates up to 88%
      versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus
      MRI, depending on the compared phase and parameter. FOI showed a higher rate of
      positive results compared to CE, US and MRI. In individual patients, FOI
      correlated significantly (p<0.05) with disease activity (Disease Activity Score
      28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56).
      FOI was normal in 97.8% of joints of controls. CONCLUSION: ICG-enhanced FOI is a
      new technology offering sensitive imaging detection of inflammatory changes in
      subjects with arthritis. FOI was more sensitive than CE and had good agreement
      with CE, US in power Doppler mode and MRI, while showing more positive results
      than these. An adequate interpretation of an FOI sequence requires a separate
      evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI
      appears to be as informative as 1.5 T MRI and US.

PMID- 22388999
TI  - Delayed dislocation of a sutureless aortic bioprosthesis: the first case.
AB  - Sutureless aortic bioprosthesis implantation is an alternative technique in high
      risk patients undergoing aortic valve replacement with a possible reduction in
      the extracorporeal circuit time and reliable haemodynamic features. A 3F Enable
      (ATS Medical-Medtronic, Inc., Minneapolis, MN, USA) has shown very good results.
      We report the first upward displacement of 3F Enable three months post
      implantation.

PMID- 22388998
TI  - Genome-wide association study of N370S homozygous Gaucher disease reveals the
      candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic
      variation.
AB  - Mutations in GBA1 gene result in defective acid beta-glucosidase and the complex
      phenotype of Gaucher disease (GD) related to the accumulation of glucosylceramide
      laden macrophages. The phenotype is highly variable even among patients harboring
      identical GBA1 mutations. We hypothesize that modifier gene(s) underlie
      phenotypic diversity in GD and performed a GWAS study in Ashkenazi Jewish
      patients with type 1 GD (GD1), homozygous for N370S mutation. Patients were
      assigned to mild, moderate, or severe disease categories using composite disease
      severity scoring systems. Whole-genome genotyping for >500,000 SNPs was performed
      to search for association signals using OQLS algorithm in 139 eligible patients.
      Several SNPs in linkage disequilibrium within the CLN8 gene locus were associated
      with the GD1 severity: SNP rs11986414 was associated with GD1 severity at P value
      1.26 * 10(-6) . Compared to mild disease, risk allele A at rs11986414 conferred
      an odds ratio of 3.72 for moderate/severe disease. Loss of function mutations in
      CLN8 causes neuronal ceroid-lipofuscinosis, but our results indicate that its
      increased expression may protect against severe GD1. In cultured skin
      fibroblasts, the relative expression of CLN8 was higher in mild GD compared to
      severely affected patients, in whom CLN8 risk alleles were overrepresented. In an
      in vitro cell model of GD, CLN8 expression was increased, which was further
      enhanced in the presence of bioactive substrate, glucosylsphingosine. Taken
      together, CLN8 is a candidate modifier gene for GD1 that may function as a
      protective sphingolipid sensor and/or in glycosphingolipid trafficking. Future
      studies should explore the role of CLN8 in pathophysiology of GD.

PMID- 22389000
TI  - Bicuspidy does not affect reoperation risk following aortic valve reimplantation.
AB  - Aortic valve reimplantation has been shown to be a safe procedure. However,
      evidences of durability in bicuspid aortic valves (BAVs) are limited in the
      literature. Between 2002 and 2011, 132 patients (mean age 61 +/- 12 years)
      underwent aortic valve reimplantation. In 24 patients (18%), aortic valve was
      bicuspid. Mean follow-up was 50 +/- 26 months (range 1-102 months) and was 99%
      complete. In-hospital mortality was 0.8% (1 patient). Survival at 1 and 5 years
      was 99 and 94%, respectively. Overall freedom from aortic valve reoperation at 1
      and 5 years was 96 and 90%, respectively, without significant difference between
      patients with bicuspid and tricuspid aortic valve. Freedom from aortic valve
      regurgitation >2+/4+, excluding patients reoperated, was at 1 and 5 years of 100
      and 99%, respectively. Patients with valve cusp repair showed a higher rate of
      aortic valve reoperation; however, only postoperative aortic regurgitation >2+/4+
      was significant risk factor for redo procedure at multivariate analysis. Aortic
      valve reimplantation in BAV without cusp repair provides excellent mid-term
      results. Further observations and longer follow-up are necessary to determine if
      BAV sparing, even in the presence of cusps alterations, could allow satisfying
      durability.

PMID- 22389001
TI  - Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression
      of transcription.
AB  - Runx2, best known for its role in regulating osteoblast-specific gene expression,
      also plays an increasingly recognized role in prostate and breast cancer
      metastasis. Using the C4-2B/Rx2(dox) prostate cancer cell line that conditionally
      expressed Runx2 in response to doxycycline treatment, we identified and
      characterized G9a, a histone methyltransferase, as a novel regulator for Runx2
      activity. G9a function was locus-dependent. Whereas depletion of G9a reduced
      expression of many Runx2 target genes, including MMP9, CSF2, SDF1, and CST7,
      expression of others, such as MMP13 and PIP, was enhanced. Physical association
      between G9a and Runx2 was indicated by co-immunoprecipitation, GST-pulldown,
      immunofluorescence, and fluorescence recovery after photobleaching (FRAP) assays.
      Since G9a makes repressive histone methylation marks and is primarily known as a
      corepressor, we further investigated the mechanism by which G9a functioned as a
      positive regulator for Runx2 target genes. Transient reporter assays indicated
      that the histone methyltransferase activity of G9a was not required for
      transcriptional activation by Runx2. Chromatin immunoprecipitation assays for
      Runx2 and G9a showed that G9a was recruited to endogenous Runx2 binding sites. We
      conclude that a subset of cancer-related Runx2 target genes require recruitment
      of G9a for their expression, but do not depend on its histone methyltransferase
      activity.

PMID- 22389002
TI  - Changes in serum collagen markers, IGF-I, and knee joint laxity across the
      menstrual cycle.
AB  - Variations in serum markers of collagen production (CICP) and degradation (ICTP),
      insulin-like growth factor I (IGF-I) and anterior knee laxity (AKL) were measured
      in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral
      contraceptives] over 5 consecutive days at menses (M1-M5, 1st pill week), the
      initial estrogen rise near ovulation (O1-O5, 2nd pill week), the initial
      progesterone rise of the early luteal phase (EL1-EL5, 3rd pill week) and post
      progesterone peak of the late luteal phase (LL1-LL5, 4th pill week). ICTP was
      higher in oral contraceptive women (5.3 +/- 1.7 vs. 3.7 +/- 1.3 ug/L; p = 0.030),
      primarily during days near ovulation and the early luteal phase when
      concentrations decreased in eumenorrheic women (p = 0.04). IGF-I concentrations
      increased during menses then decreased and remained lower during the early and
      late luteal phase in oral contraceptive women, resulting in lower concentrations
      compared to eumenorrheic women at EL2 and LL1 (p = 0.03). CICP decreased in early
      and late luteal days (p <0.01), and there was a trend toward lower concentrations
      in eumenorrheic versus oral contraceptive women (85.7 +/- 35.7 ng/ml vs. 123.2 +/
      49.8 ng/ml; p = 0.07). Lower CICP and greater IGF-I concentrations predicted
      greater AKL across the 20 cycle days in both groups (R(2)  = 0.310 and 0.400).
      Sex hormone concentration changes across the menstrual cycle are of sufficient
      magnitude to influence collagen metabolism, and may indirectly influence knee
      structure and function.

PMID- 22389003
TI  - A case of esomeprazole-induced transient diabetes and hepatitis: the role of
      liver inflammation in the pathogenesis of insulin resistance.
AB  - We describe a case report of a patient who developed transient type 2 diabetes
      after a drug-induced (esomeprazole) sub-acute hepatitis. This case evidences the
      pathophysiological relevance, also in humans, of liver inflammation in the
      pathogenesis of type 2 diabetes. 

PMID- 22389004
TI  - Polycystic ovary syndrome is not associated with genetic variants that mark risk
      of type 2 diabetes.
AB  - Polycystic ovary syndrome (PCOS) is a disorder of irregular menses,
      hyperandrogenism and/or polycystic ovary morphology. A large proportion of women
      with PCOS also exhibit insulin resistance, beta-cell dysfunction, impaired
      glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that
      genetic variants that predispose to risk of T2D also result in risk of PCOS.
      Variants robustly associated with T2D in candidate gene or genome-wide
      association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of
      European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years.
      Metabolic, reproductive and anthropomorphic data were examined as a function of
      the T2D variants. All genetic association analyses were adjusted for age, BMI and
      ancestry and were reported after correction for multiple testing. There was a
      nominal association between variants in KCNJ11 and risk of PCOS. However, a risk
      score of 33 independent T2D-associated variants from GWAS was not significantly
      associated with PCOS. T2D variants were associated with PCOS phenotype parameters
      including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with
      triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes
      risk variants are not important risk variants for PCOS.

PMID- 22389008
TI  - Fractures of the femoral head: a long-term follow-up study.
AB  - The femoral head fracture has become an increasingly frequent injury, usually
      sustained by individuals during high-energy trauma. Regardless of the type of
      treatment, long-term consequences, as avascular necrosis, post-traumatic
      arthritis, and heterotopic ossification, may complicate the clinical outcome
      leading to variable degree of disability. The aim of this study was to review the
      clinical and radiological long-term follow-up of patients with a fracture of the
      femoral head. Between January 1985 and January 2002, twenty-one patients with
      mean age 42.0 +/- 15.9 years (range, 21-70 years) with a fracture of the femoral
      head were evaluated retrospectively. According to Pipkin's classification, there
      were four type I, nine type II, and eight type IV fractures. Functional outcomes
      were measured using the Merle d'Aubigne-Postel and Thompson-Epstein scoring
      scale. Heterotopic calcifications was graded according to the Brooker
      classification. All patients were followed up from 12 to 210 months, with an
      average of 81.19 +/- 37.4 months. The average Merle d'Aubigne-Postel score was
      12.9 +/- 4.5. According to the Thompson-Epstein criteria, eight patients had
      excellent results, eight patients good, two patients fair, and three patients
      poor results. Overall, almost all (95. 2%) patients were determined to have
      radiographic criteria of post-traumatic arthritis (PA). Ten patients (47.6%) had
      a mild PA, seven patients (33.3%) had a moderate PA, and three patients (14.2%)
      had a severe PA. Open reduction and internal fixation of the fragments provided
      better results in comparison to excision. Although degenerative changes of the
      hip were observed in almost all patients, most severe case occurred in the
      excision group.

PMID- 22389009
TI  - Interaction of L-leucyl-L-leucyl-L-leucine thin film with water and organic
      vapors: receptor properties and related morphology.
AB  - The ability of highly ordered tripeptide structures to keep or change their
      morphology in contact with organic vapors was studied. A thin film of tripeptide
      L-leucyl-L-leucyl-L-leucine (LLL) was prepared having microcrystals and
      nanocrystals on its surface, which are stable upon vacuum drying but become
      objects of selective morphology change after a contact with vapors of organic
      solvents. Fine separate LLL crystals and their agglomerates of submicron and
      larger dimensions were observed by atomic force microscopy and scanning electron
      microscopy. After saturation with guest vapors, these crystals can remain intact
      or change their morphology with the increase in size or complete destruction
      depending on the guest molecular structure. The crystals completely lose their
      shape after the binding of pyridine vapors. The other studied guests produce much
      smaller transformations or have no effect on crystal morphology despite being
      sorbed by solid LLL, which was shown using quartz crystal microbalance sensor.
      The observed size-exclusion effect for guest sorption by LLL was found to be
      broken by the same guests that can change the initial crystal shape. This helps
      to explain the morphology changes of LLL crystals after the guest sorption and
      release.

PMID- 22389010
TI  - Using BLAT to find sequence similarity in closely related genomes.
AB  - The BLAST-Like Alignment Tool (BLAT) is used to find genomic sequences that match
      a protein or DNA sequence submitted by the user. BLAT is typically used for
      searching similar sequences within the same or closely related species. It was
      developed to align millions of expressed sequence tags and mouse whole-genome
      random reads to the human genome at a higher speed. It is freely available either
      on the Web or as a downloadable stand-alone program. BLAT search results provide
      a link for visualization in the University of California, Santa Cruz (UCSC)
      Genome Browser, where associated biological information may be obtained. Three
      example protocols are given: using an mRNA sequence to identify the exon-intron
      locations and associated gene in the genomic sequence of the same species, using
      a protein sequence to identify the coding regions in a genomic sequence and to
      search for gene family members in the same species, and using a protein sequence
      to find homologs in another species.

PMID- 22389011
TI  - The Bluejay genome browser.
AB  - The Bluejay genome browser is a stand-alone visualization tool for the multi
      scale viewing of annotated genomes and other genomic elements. Bluejay allows
      users to customize display features to suit their needs, and produces publication
      quality graphics. Bluejay provides a multitude of ways to interrelate biological
      data at the genome scale. Users can load gene expression data into a genome
      display for expression visualization in context. Multiple genomes can be compared
      concurrently, including time series expression data, based on Gene Ontology
      labels. External, context-sensitive biological Web Services are linked to the
      displayed genomic elements ad hoc for in-depth genomic data analysis and
      interpretation. Users can mark multiple points of interest in a genome by
      creating waypoints, and exploit them for easy navigation of single or multiple
      genomes. Using this comprehensive visual environment, users can study a gene not
      just in relation to its genome, but also its transcriptome and evolutionary
      origins. Written in Java, Bluejay is platform-independent and is freely available
      from http://bluejay.ucalgary.ca.

PMID- 22389012
TI  - Identifying proteomic LC-MS/MS data sets with Bumbershoot and IDPicker.
AB  - The identification of peptides and proteins by LC-MS/MS requires the use of
      bioinformatics. Tools developed in the Tabb Laboratory contribute significant
      flexibility and discrimination to this process. The Bumbershoot tools (MyriMatch,
      DirecTag, TagRecon, and Pepitome) enable the identification of peptides
      represented by MS/MS scans. All of these tools can work directly from instrument
      capture files of multiple vendors, such as Thermo RAW format, or from standard
      XML-based formats, such as mzML or mzXML. Peptide identifications are written to
      mzIdentML or pepXML format. Protein assembly is handled by the IDPicker
      algorithm. Raw identifications are filtered to a confident set by use of the
      target-decoy strategy. IDPicker arranges large sets of input files into a
      hierarchy for reporting, and the software applies a parsimony algorithm to report
      the smallest possible number of proteins to explain the observed peptides. This
      protocol details the use of these tools for new users.

PMID- 22389013
TI  - Identification of peptide features in precursor spectra using Hardklor and
      Kronik.
AB  - Hardklor and Kronik are software tools for feature detection and data reduction
      of high-resolution mass spectra. Hardklor is used to reduce peptide isotope
      distributions to a single monoisotopic mass and charge state, and can deconvolve
      overlapping peptide isotope distributions. Kronik filters, validates, and
      summarizes peptide features identified with Hardklor from data obtained during
      liquid chromatography mass spectrometry (LC-MS). Both software tools contain a
      simple user interface and can be run from nearly any desktop computer. These
      tools are freely available from
      http://proteome.gs.washington.edu/software/hardklor.

PMID- 22389014
TI  - LC-MS data processing with MAVEN: a metabolomic analysis and visualization
      engine.
AB  - MAVEN is an open-source software program for interactive processing of LC-MS
      based metabolomics data. MAVEN enables rapid and reliable metabolite quantitation
      from multiple reaction monitoring data or high-resolution full-scan mass
      spectrometry data. It automatically detects and reports peak intensities for
      isotope-labeled metabolites. Menu-driven, click-based navigation allows
      visualization of raw and analyzed data. Here we provide a User Guide for MAVEN.
      Step-by-step instructions are provided for data import, peak alignment across
      samples, identification of metabolites that differ strongly between biological
      conditions, quantitation and visualization of isotope-labeling patterns, and
      export of tables of metabolite-specific peak intensities. Together, these
      instructions describe a workflow that allows efficient processing of raw LC-MS
      data into a form ready for biological analysis.

PMID- 22389017
TI  - High-performance air-stable ambipolar organic field-effect transistor based on
      tris(phthalocyaninato) europium(III).
AB  - A novel sandwich-type tris(phthalocyaninato) europium triple-decker complex
      bearing peripheral electron-withdrawing groups (see center of figure) is used to
      fabricate a field-effect transistor by the quasi-Langmuir-Schaefer method. The
      air-stable, single-component ambipolar OFET device displays the best carrier
      properties of a device fabricated by solution processing of a single
      phthalocyanine derivative so far, which makes the complex very promising for
      applications in nanoelectronics.

PMID- 22389016
TI  - Acute megakaryoblastic leukemia and severe pulmonary fibrosis in a child with
      Down syndrome: successful treatment with ultra low-dose cytarabine using GATA1
      mutation to monitor minimal residual disease.

PMID- 22389018
TI  - Identifying, understanding and overcoming barriers to medication error reporting
      in hospitals: a focus group study.
AB  - OBJECTIVES: The under-reporting of medication errors can compromise patient
      safety. A qualitative study was conducted to enhance the understanding of
      barriers to medication error reporting in healthcare organisations. METHODS:
      Focus groups (with physicians, pharmacists and nurses) and in-depth interviews
      (with risk managers) were used to identify medication error reporting beliefs and
      practices at four community hospitals in Nova Scotia, Canada. Audio tapes were
      transcribed verbatim and analysed for thematic content using the template style
      of analysis. The development and analysis of this study were guided by Safety
      Culture Theory. RESULTS: Incentives for medication error reporting were
      thematised into three categories: patient protection, provider protection and
      professional compliance. Barriers to medication error reporting were thematised
      into five categories: reporter burden, professional identity, information gap,
      organisational factors and fear. Facilitators to encourage medication error
      reporting were classified into three categories: reducing reporter burden,
      closing the communication gap and educating for success. Participants indicated
      they would report medication errors more frequently if reporting were made
      easier, if they were adequately educated about reporting, and if they received
      timely feedback. CONCLUSIONS: Study results may lead to a better understanding of
      the barriers to medication error reporting, why these barriers exist and what can
      be done to successfully overcome them. These results could be used by hospitals
      to encourage reporting of medication errors and ultimately make organisational
      changes leading to a reduction in the incidence of medication errors and an
      improvement in patient safety.

PMID- 22389019
TI  - Defining impact of a rapid response team: qualitative study with nurses,
      physicians and hospital administrators.
AB  - OBJECTIVE: The objective of this study was to qualitatively describe the impact
      of a Rapid Response Team (RRT) at a 944-bed, university-affiliated hospital.
      METHODS: We analysed 49 open-ended interviews with administrators, primary team
      attending physicians, trainees, RRT attending hospitalists, staff nurses, nurses
      and respiratory technicians. RESULTS: Themes elicited were categorised into the
      domains of (1) morale and teamwork, (2) education, (3) workload, (4) patient
      care, and (5) hospital administration. Positive implications beyond improved care
      for acutely ill patients were: increased morale and empowerment among nurses,
      real-time redistribution of workload for nurses (reducing neglect of non-acutely
      ill patients during emergencies), and immediate access to expert help. Negative
      implications were: increased tensions between nurses and physician teams, a
      burden on hospitalist RRT members, and reduced autonomy for trainees.
      CONCLUSIONS: The RRT provides advantages that extend well beyond a reduction in
      rates of transfers to intensive care units or codes but are balanced by certain
      disadvantages. The potential impact from these multiple sources should be
      evaluated to understand the utility of any RRT programme.

PMID- 22389020
TI  - Medical emergency team calls in the radiology department: patient characteristics
      and outcomes.
AB  - OBJECTIVE: We sought to identify the characteristics of patients who experience
      medical emergency team calls in the radiology department (MET-RD) and the
      relationship between these characteristics and patient outcomes.
      DESIGN/PARTICIPANTS: Retrospective review of 111 inpatient MET-RD calls (May 2008
      April 2010). SETTING: Academic medical centre with a well established MET system.
      MEASUREMENTS: The characteristics of patients before, during and after transport
      to radiology were extracted from medical records and administrative databases.
      These characteristics were compared between patients with good and poor outcomes.
      MAIN RESULTS: The majority of patients who experience MET-RD calls had a Charlson
      Comorbidity Index >=4 and were from non-intensive care units (60%). Almost half
      (43%) of MET-RD calls occurred during patients' first day in hospital. Patients
      commonly arrived with nasal cannula oxygen (38%), recent tachypnoea (28%) and
      tachycardia (34%). A minority (16%) fulfilled MET call criteria in the 12 h
      before the MET-RD. MET-RD etiologies were cardiac (41%), respiratory (29%) or
      neurological (25%), and occurred most frequently during CT (44%) and MRI (22%)
      testing. Post MET-RD, the majority of patients (70%) required a higher level of
      care. Death before discharge (25%) was associated with need for cardiovascular
      support prior to RD transport (p=0.02), need for RD monitoring (p=0.02) and need
      for heightened RD surveillance (p=0.04). CONCLUSIONS: The majority of patients
      who experienced MET-RD calls came from non-intensive care units, with
      comorbidities and vital sign alterations prior to arrival at the RD. Risk
      appeared to be increased for those requiring CT and MRI. These findings suggest
      that prior identification of a subset of patients at risk of instability in the
      RD may be possible.

PMID- 22389021
TI  - Exploring the role of salient distracting clinical features in the emergence of
      diagnostic errors and the mechanisms through which reflection counteracts
      mistakes.
AB  - BACKGROUND: Flaws in clinical reasoning are present in most diagnostic errors and
      occur even when physicians have enough knowledge to solve the problem. Deliberate
      reflection has been shown to improve diagnoses. The sources of faulty reasoning
      and how reflection counteracts them remain largely unknown. OBJECTIVE: To explore
      the causes of faulty reasoning and the mechanisms through which reflection
      neutralises them by investigating the influence of salient distracting clinical
      features on diagnostic decision-making. DESIGN AND SETTING: In a prior study, 34
      internal medicine residents and 50 medical students of the Erasmus Medical
      Centre, Rotterdam, diagnosed four clinical cases by means of non-analytical
      reasoning and four by reflective reasoning. In the secondary analysis of the data
      presented here, five internists independently evaluated the diagnoses and
      examined the nature of the diagnostic errors in relation to case features that
      gave rise to these errors. MAIN OUTCOMES: Frequency of incorrect diagnoses caused
      by salient distracting features made through reflective and non-analytical
      reasoning. RESULTS: Among residents, reflective reasoning (Mean diagnostic
      accuracy score (M)=2.09, 95% CI 1.77 to 2.40) led to a significantly higher
      number of correct diagnoses than non-analytical reasoning (M=1.71, 95% CI 1.37 to
      2.04; p=0.03). This higher diagnostic accuracy was associated with fewer
      incorrect diagnoses triggered by salient distracting clinical features (M=0.47,
      95% CI 0.26 to 0.68) compared with non-analytical reasoning (M=0.85, 95% CI 0.59
      to 1.11; p=0.02). Students did not benefit from reflection to improve diagnoses.
      CONCLUSION: Salient features in a case tend to attract physicians' attention and
      may misdirect diagnostic reasoning when they turn out to be unrelated to the
      problem, causing errors. Reflection helps by enabling physicians to overcome the
      influence of distracting features. The lack of effect for students suggests that
      this is only possible when there is enough knowledge to recognise which features
      discriminate between alternative diagnoses.

PMID- 22389022
TI  - Association of National Hospital Quality Measure adherence with long-term
      mortality and readmissions.
AB  - BACKGROUND: In existing studies, the association between adherence with
      recommended hospital care processes and subsequent outcomes has been
      inconsistent. This has substantial implications because process measure scores
      are used for accountability, quality improvement and reimbursement. Our
      investigation addresses methodological concerns with previous studies to better
      clarify the process-outcomes association for three common conditions. METHODS:
      The study included all patients discharged from Massachusetts General Hospital
      between 1 July 2004 and 31 December 2007 with a principle diagnosis of acute
      myocardial infarction (AMI), heart failure (HF) or pneumonia (PN) who were
      eligible for at least one National Hospital Quality Measure. The number of
      patients analysed varied by measure (374 to 3020) depending on Centers for
      Medicare and Medicaid Services eligibility criteria. Hospital data were linked
      with state administrative data to determine mortality and readmissions. For
      patients with multiple admissions, the time-weighted impact of measure failures
      on mortality was estimated using exponential decay functions. All patients had
      follow-up for at least 1 year or until death or readmission. Cox models were used
      to estimate HRs adjusted for transfer status, age, gender, race, census block
      group socioeconomic status, number of Elixhauser comorbidities, and do not
      resuscitate orders. RESULTS: Adjusted survival and freedom from readmission for
      AMI and PN showed superior results for 100% and 50-99% adherence compared with 0
      49% adherence. For HF, the results were inconsistent and sometimes paradoxical,
      although several individual measures (eg, ACE inhibitor/angiotensin receptor
      blockade) were associated with improved outcomes. CONCLUSION: Adherence with
      recommended AMI and PN care processes is associated with improved long-term
      outcomes, whereas the results for HF measures are inconsistent. The evidence base
      for all process measures must be critically evaluated, including the strength of
      association between these care processes and outcomes in real-world populations.
      Some currently recommended processes may not be suitable as accountability
      measures.

PMID- 22389023
TI  - Hole mediated coupling in Sr2Nb2O7 for visible light photocatalysis.
AB  - The band gap reduction and effective utilization of visible solar light are
      possible by introducing the anionic hole-hole mediated coupling in
      Sr(2)Nb(2)O(7). By using the first principles calculations, we have investigated
      the mono- and co-anionic doping (S, N and C) in layered perovskite Sr(2)Nb(2)O(7)
      for the visible-light photocatalysis. Our electronic structure and optical
      absorption study shows that the mono- (N and S) and co-anionic doped (N-N and C
      S) Sr(2)Nb(2)O(7) systems are promising materials for the visible light
      photocatalysis. The calculated binding energies show that if the hole-hole
      mediated coupling could be introduced, the co-doped systems would be more stable
      than their respective mono-doped systems. Optical absorption curves indicate that
      doping S, (N-N) and (C-S) in Sr(2)Nb(2)O(7) can harvest a longer wavelength of
      the visible light spectrum as compared to the pure Sr(2)Nb(2)O(7) for efficient
      photocatalysis.

PMID- 22389025
TI  - Fluorescence turn-on detection of hypochlorous acid via HOCl-promoted
      dihydrofluorescein-ether oxidation and its application in vivo.
AB  - We report three new water-soluble dihydrofluorescein-ether probes FCN1, FCN2 and
      FCN3 for the detection of hypochlorous acid (HOCl), which were designed on the
      basis of a specific HOCl-promoted oxidation reaction. This work also provided a
      useful method to monitor the accumulated HOCl in specific organelles using a
      zebrafish model.

PMID- 22389024
TI  - Mucosal tonometry as early warning of gastrojejunal leak in laparoscopic Roux-en
      y gastric bypass.
AB  - The laparoscopic Roux-en-Y gastric bypass (LRYGB) is the standard surgical
      procedure for morbidly obese patients in many centers worldwide. The
      gastrojejunal anastomosis (GJA) leak has a 2 % incidence and a 10 % mortality.
      This prospective study aims to test gastroenteric tonometry as an early warning
      of GJA leak risk. A nasogastric tube with tonometric capability was used to
      monitor gastroenteric mucosal carbon dioxide partial pressure (PgeCO2) in 32
      consecutive patients during the first 24 to 72 postoperative hours after LRYGB.
      Sensitivity was 100 %, specificity 96.77 %, likelihood ratio 31, and area under
      receiver operating characteristic curve 0.984. The only early gastrojejunal leak
      occurred to the patient with maximal PgeCO2 (13.9 kPa) of the cohort. The
      remaining patients kept a PgeCO2 below 11 kPa except one; none of these developed
      early GJA leak. Mucosal gastroenteric tonometry may be a useful predictor of
      early GJA leak of the LRYGB.

PMID- 22389026
TI  - Inhibitory effect of phenylbutanoid-rich Zingiber cassumunar extracts on nitric
      oxide production by murine macrophage-like RAW264.7 cells.
AB  - Four phenylbutanoids, (E)-4-(3,4-dimethoxyphenyl)but-3-en-l-ol (I), (E)-4-(3,4
      dimethoxyphenyl)but-3-en-l-yl acetate (II), (E)-1-(3,4-dimethoxyphenyl)butadiene
      (III) and (E)-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene
      (IV), isolated from Zingiber cassumunar, were used as standard markers for
      quantitative determination and preparation of phenylbutanoid-enriched Z.
      cassumunar extracts (PZEs). A reversed-phase HPLC method was established for the
      simultaneous determination of the phenylbutanoids in Z. cassumunar extracts.
      Systematic extraction studies to maximize phenylbutanoid content revealed that
      hexane was the most appropriate solvent for extraction. A one-step purification
      of the hexane crude extract of Z. cassumunar, using silica gel vacuum
      chromatography, provided the PZEs. The content of phenylbutanoids in the PZEs was
      up to 48.3% w/w dry weight. The anti-inflammatory activity of PZEs via inhibition
      of nitric oxide production by murine macrophage-like RAW264.7 cells was stronger
      than those of the four individual phenylbutanoids, the crude hexane extract and
      the essential oil of Z. cassumunar.

PMID- 22389027
TI  - Early specification of GAD67 subventricular derived olfactory interneurons.
AB  - Olfactory bulb interneurons are continuously generated in the subventricular zone
      (SVZ) and migrate along the rostral migratory stream (RMS) into the olfactory
      bulb (OB) where the majority becomes local GABAergic interneurons. We previously
      showed that SVZ-derived progenitor cells expressed glutamic acid decarboxylase 65
      kDa (GAD65) very early in the migratory pathway. However, only approximately half
      of OB GABAergic interneurons use GAD65, an equal number express the 67 kDa GAD
      enzyme. To investigate the differentiation of these GABAergic interneurons we
      examined their migration in a transgenic mouse expressing green fluorescent
      protein (GFP) under the control of the GAD67 promoter. In adult, GFP was
      expressed by a subpopulation of migratory cells in the SVZ and along the RMS.
      Using Doublecortin (DCX) as a marker of migrating neuroblasts and
      bromodeoxyuridine (BrdU) incorporation, we show that these GAD67-GFP neurons co
      express DCX and incorporate BrdU indicating they are newly born migratory
      neuroblasts. This is similar to GAD65 transgene expression, and in contrast to
      dopaminergic interneuron transgene expression which occurs only after cells reach
      the olfactory bulb. Although the GAD65/67 transgenes are expressed early in
      migration, there is minimal protein production in the cells prior to reaching the
      OB. These results suggest that migrating SVZ-derived neuroblasts acquire
      GABAergic identity prior to reaching their final location in the olfactory bulb.

PMID- 22389028
TI  - Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a
      rat model of intestinal ischemia/reperfusion.
AB  - The purpose of this study was to investigate the role of infliximab on acute lung
      injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male
      Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab;
      each group contain 10 animals. Sham group animals underwent laparotomy without
      I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior
      mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab
      group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously.
      All animals were sacrificed at the end of reperfusion and lung tissues samples
      were obtained for biochemical and histopathological investigation in all groups.
      To date, no more biochemical and histopathological changes on intestinal I/R
      injury in rats by infliximab treatment have been reported. Infliximab treatment
      significantly decreased the elevated tissue malondialdehyde levels and increased
      of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in
      lung tissues samples. Intestinal I/R caused severe histopathological injury
      including edema, hemorrhage, increased thickness of the alveolar wall and a great
      number of inflammatory cells that infiltrated the interstitium and alveoli.
      Infliximab treatment significantly attenuated the severity of intestinal I/R
      injury. Furthermore, there is a significant reduction in the activity of
      inducible nitric oxide synthase and arise in the expression of surfactant protein
      D in lung tissue of acute lung injury induced by intestinal I/R with infliximab
      therapy. It was concluded that infliximab treatment might be beneficial in acute
      lung injury, therefore, shows potential for clinical use. Because of its anti
      inflammatory and antioxidant effects, infliximab pretreatment may have protective
      effects in acute lung injury induced by intestinal I/R.

PMID- 22389029
TI  - An analysis of clinicopathological features and prognosis by comparing hepatoid
      adenocarcinoma of the stomach with AFP-producing gastric cancer.
AB  - OBJECTIVE: To investigate the differences between alpha-fetoprotein-producing
      gastric cancer (AFPPGC) and hepatoid adenocarcinoma of the stomach (HAS), and the
      clinicopathologic features and prognosis of HAS. METHODS: From 1996 to 2007,
      there were 111 patients with elevated serum level of alpha-fetoprotein (AFP)
      preoperatively in Fudan University Shanghai Cancer Center. Primary lesions of 104
      patients were stained positively for AFP. Among these patients, 45 patients were
      diagnosed as HAS. The clinicopathologic characteristics and prognostic factors of
      AFPPGC and HAS were analyzed. Additionally, 208 stage-matched AFP-negative
      gastric cancer patients were selected as control. RESULTS: Immunohistochemically,
      the tumor cells were positive for AFP in AFPPGC. Histologically, the polygonal
      tumor cells were arranged in trabecular fashion or solid nests separated by
      narrow fibrous stroma composed of sinusoid-like capillaries in HAS. The survival
      rates of the three groups were statistically different (P < 0.01). CONCLUSION:
      AFP-producing gastric cancer and HAS had more aggressive behavior than that of
      common gastric cancer. The prognosis of HAS was poorer than that of AFPPGC,
      therefore it should be distinguished from the latter.

PMID- 22389030
TI  - Proton transfer and polarity changes in ionic liquid-water mixtures: a
      perspective on hydrogen bonds from ab initio molecular dynamics at the example of
      1-ethyl-3-methylimidazolium acetate-water mixtures--part 1.
AB  - The ionic liquid 1-ethyl-3-methylimidazolium acetate [C(2)C(1)Im][OAc] shows a
      great potential to dissolve strongly hydrogen bonded materials, related with the
      presence of a strong hydrogen bond network in the pure liquid. A first step
      towards understanding the solvation process is characterising the hydrogen
      bonding ability of the ionic liquid. The description of hydrogen bonds in ionic
      liquids is a question under debate, given the complex nature of this media. The
      purpose of the present article is to rationalise not only the existence of
      hydrogen bonds in ionic liquids, but also to analyse their influence on the
      structure of the pure liquid and how the presence of water, an impurity inherent
      to ionic liquids, affects this type of interaction. We perform an extensive study
      using ab initio molecular dynamics on the structure of mixtures of the ionic
      liquid 1-ethyl-3-methylimidazolium acetate with water, at different water
      contents. Hydrogen bonds are present in the pure liquid, and the presence of
      water modifies and largely disturbs the hydrogen bond network of the ionic
      liquid, and also affects the formation of other impurities (carbenes) and the
      dipole moment of the ions. The use of ab initio molecular dynamics is the
      recommended tool to explore hydrogen bonding in ionic liquids, as an explicit
      electronic structure calculation is combined with the study of the condensed
      phase.

PMID- 22389031
TI  - The expression and role of non-canonical (PKC) signaling in nucleus pulposus cell
      metabolism.
AB  - Canonical Wnt/beta-catenin (hereafter Wnt) signaling regulates the proliferation
      and differentiation of various cell types. However, the role of non-canonical
      signaling including protein kinase C (PKC) signaling has not been investigated in
      intervertebral disc (IVD) cells. The aim of this study was to elucidate whether
      the activation of PKC signaling act to modulate Wnt signaling in IVD cells. We
      performed several reporter assays, real-time reverse transcription polymerase
      chain reaction (RT-PCR), immunohistochemical and immunofluorescence analyses, and
      western blot analyses using rat nucleus pulposus (NP) cells. We also examined the
      cell proliferation and cell cycle distribution under phorbol 12-myristate 13
      acetate (PMA) stimulation, a known activator of PKC signaling. We found that NP
      cells exhibited decreased beta-catenin mRNA and protein levels upon stimulation
      with PMA. PMA treatment promoted proliferation and cell cycle progression in a
      time- and dose-dependent manner. In addition, activation of the PKC signaling
      also regulated the expression of aggrecan. Finally, activation by PMA induced the
      expression of several PKC isoforms in NP cells. It is concluded that activation
      of PKC signaling might lead to an increase in matrix synthesis and cell
      proliferation, thereby inhibiting IVD degeneration. Crosstalk in these signaling
      pathways plays an important role in the regulation of IVD homeostasis.

PMID- 22389032
TI  - Sequence of treatments for adults with primary immune thrombocytopenia.
AB  - Management of adults with primary immune thrombocytopenia (ITP) has changed
      dramatically in the past 10 years. New regimens of corticosteroids for first-line
      treatment have been introduced and are currently being evaluated in a randomized
      clinical trial. Many patients may not have durable remissions with initial
      corticosteroid regimens and may require additional, second-line, treatment. For
      these patients, rituximab has been increasingly used, as it has for other
      autoimmune disorders, and new thrombopoietin (TPO)-receptor agonists have been
      developed. Although splenectomy was the first effective and remains the most
      effective treatment for ITP, inducing durable complete remissions in 66% of
      patients, rituximab and TPO-receptor agonists are now additional options for
      second-line treatment. For patients who continue to have severe and symptomatic
      thrombocytopenia following failure of multiple treatments, including splenectomy
      and rituximab, the TPO-receptor agonists are effective as third-line treatment
      for maintaining safe platelets counts to prevent bleeding symptoms in most
      patients.

PMID- 22389035
TI  - Planned stereotactic biopsy of a bilateral thalamic glioma in a patient
      presenting with unilateral tremor.

PMID- 22389036
TI  - Microscope transsphenoidal surgery.
AB  - BACKGROUND: The transsphenoidal approach to the pituitary using the microscope
      has undergone continuous modification since its introduction by Hardy over 50
      years ago. It is one of the most effective and safest of major neurosurgical
      procedures with excellent outcomes and low complication rates. METHODS: Although
      being displaced by the endoscopic approach, it remains the 'gold standard' for a
      number of pituitary conditions such as Cushing's tumours, and for the majority of
      the remainder, has yet to be overtaken in outcome results by the endoscopic
      approach. CONCLUSION: This description of the endonasal 'septal pushover'
      technique is from an author with experience in nearly 4,000 cases. The anatomy is
      described, and the step-by-step approach and tumour removal for micro- and
      pituitary macroadenomas are given. Complications and their avoidance are
      overviewed.

PMID- 22389037
TI  - Intracranial arachnoid cyst family with autosomal recessive trait mapped to
      chromosome 6q22.31-23.2.
AB  - BACKGROUND: Arachnoid cysts are congenital fluid-filled compartments within the
      cerebrospinal fluid cisterns and cerebral fissures. They most commonly occur
      sporadically, and familial occurrence has rarely been reported. In this study, we
      showed the first genetic linkage in the literature in a pure intracranial
      arachnoid cyst family with autosomal recessive trait. METHODS: We identified an
      intracranial arachnoid cyst family in southern Turkey whose six of seven
      offspring had intracranial arachnoid cysts in different localizations, and
      collected venous blood from seven offspring of the family. Whole-genome linkage
      analysis was performed in all offspring. RESULTS: A theorical maximum logarithm
      of the odds score of 4.6 was identified at chromosome 6q22.31-23.2. This result
      shows strong genetic linkage to this locus. CONCLUSIONS: We present the first
      genetic linkage analysis result in a pure intracranial arachnoid cyst family in
      literature. Further investigation of this linkage area can reveal a causative
      gene causing the intracranial arachnoid cyst phenotype and can illuminate the
      pathogenesis of this disease.

PMID- 22389040
TI  - 2012 Provisional classification criteria for polymyalgia rheumatica: a European
      League Against Rheumatism/American College of Rheumatology collaborative
      initiative.
AB  - The objective of this study was to develop European League Against
      Rheumatism/American College of Rheumatology classification criteria for
      polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month
      prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR
      comparison subjects with conditions mimicking PMR. A scoring algorithm was
      developed based on morning stiffness >45 minutes (2 points), hip pain/limited
      range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated
      protein antibody (2 points), and absence of peripheral joint pain (1 point). A
      score >=4 had 68% sensitivity and 78% specificity for discriminating all
      comparison subjects from PMR. The specificity was higher (88%) for discriminating
      shoulder conditions from PMR and lower (65%) for discriminating RA from PMR.
      Adding ultrasound, a score >=5 had increased sensitivity to 66% and specificity
      to 81%. According to these provisional classification criteria, patients >=50
      years old presenting with bilateral shoulder pain, not better explained by an
      alternative pathology, can be classified as having PMR in the presence of morning
      stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte
      sedimentation rate, and new hip pain. These criteria are not meant for diagnostic
      purposes.

PMID- 22389041
TI  - Provisional classification [corrected] criteria for polymyalgia rheumatica:
      moving beyond clinical intuition?

PMID- 22389042
TI  - DNA methylation in amphioxus: from ancestral functions to new roles in
      vertebrates.
AB  - In vertebrates, DNA methylation is an epigenetic mechanism that modulates gene
      transcription, and plays crucial roles during development, cell fate maintenance,
      germ cell pluripotency and inheritable genome imprinting. DNA methylation might
      also play a role as a genome defense mechanism against the mutational activity
      derived from transposon mobility. In contrast to the heavily methylated genomes
      in vertebrates, most genomes in invertebrates are poorly or just moderately
      methylated, and the function of DNA methylation remains unclear. Here, we review
      the DNA methylation system in the cephalochordate amphioxus, which belongs to the
      most basally divergent group of our own phylum, the chordates. First, surveys of
      the amphioxus genome database reveal the presence of the DNA methylation
      machinery, DNA methyltransferases and methyl-CpG-binding domain proteins. Second,
      comparative genomics and analyses of conserved synteny between amphioxus and
      vertebrates provide robust evidence that the DNA methylation machinery of
      amphioxus represents the ancestral toolkit of chordates, and that its expansion
      in vertebrates was originated by the two rounds of whole-genome duplication that
      occurred in stem vertebrates. Third, in silico analysis of CpGo/e ratios
      throughout the amphioxus genome suggests a bimodal distribution of DNA
      methylation, consistent with a mosaic pattern comprising domains of methylated
      DNA interspersed with domains of unmethylated DNA, similar to the situation
      described in ascidians, but radically different to the globally methylated
      vertebrate genomes. Finally, we discuss potential roles of the DNA methylation
      system in amphioxus in the context of chordate genome evolution and the origin of
      vertebrates.

PMID- 22389043
TI  - Transposon diversity is higher in amphioxus than in vertebrates: functional and
      evolutionary inferences.
AB  - Transposable elements (TEs) are main components of eukaryote genomes-up to 50% in
      some vertebrates-which can replicate and jump to new locations. TEs contribute to
      shape genome evolution, actively by creating new genes (or exons) or altering
      gene expression as consequence of transposition, and passively by serving as
      illegitimate recombinational hotspots. Analysis of amphioxus TEs can help to shed
      light on the ancestral status of chordate TEs and to understand genome evolution
      in cephalochordates and early vertebrates. The Branchiostoma floridae genome
      project has revealed that TE content constitutes ~28% of the amphioxus genome.
      Amphioxus TEs belong to more than 30 superfamilies, which represent a higher
      diversity than in vertebrates. Amphioxus TE families are also highly
      heterogeneous as generally none of their members are drastically more abundant
      than others, and none of the TEs seems to have suffered any massive expansion.
      Such diversity and heterogeneity make the amphioxus genome not to be particularly
      prone to major evolutionary changes mediated by TEs, and therefore favoring
      genomic evolutionary stasis. Comparison of TE diversity and content between
      amphioxus and vertebrates allows us to discuss whether or not a burst of TEs
      happened after the two rounds of whole-genome duplication that occurred during
      early vertebrate evolution.

PMID- 22389044
TI  - Discovery and characterization of Coturnix chinensis avian beta-defensin 10, with
      broad antibacterial activity.
AB  - A novel avian beta-defensin (AvBD), AvBD10, was discovered in the liver and bone
      marrow tissues from Chinese painted quail (Coturnix chinensis) in the present
      study. The complete nucleotide sequence of quail AvBD10 contains a 207-bp open
      reading frame that encodes 68 amino acids. The quail AvBD10 was expressed widely
      in all the tissues from quails except the tongue, crop, breast muscle, and thymus
      and was highly expressed in the bone marrow. In contrast to the expression
      pattern of AvBD10 in tissues from quail, the chicken AvBD10 was expressed in all
      21 tissues from the layer hens investigated, with a high level of expression in
      the kidney, lung, liver, bone marrow, and Harderian glands. Recombinant
      glutathione S-transferase (GST)-tagged AvBD10s of both quail and chicken were
      produced and purified by expression of the two cDNAs in Escherichia coli,
      respectively. In addition, peptide according to the respective AvBD10s sequence
      was synthesized, named synthetic AvBD10s. As expected, both recombinant GST
      tagged AvBD10s and synthetic AvBD10s of quail and chicken exhibited similar
      bactericidal properties against most bacteria, including Gram-positive and Gram
      negative forms. However, no significant bactericidal activity was found for quail
      recombinant GST-tagged AvBD10 against Salmonella choleraesuis or for chicken
      recombinant GST-tagged AvBD10 against Proteus mirabilis.

PMID- 22389045
TI  - Efficient dynamic kinetic resolution of racemic secondary alcohols by a
      chemoenzymatic system using bifunctional iridium complexes with C-N chelate amido
      ligands.
AB  - The combined catalyst system of bifunctional amidoiridium complexes derived from
      benzylic amines with CALB was found to provide a range of chiral acetates from
      racemic secondary alcohols in excellent yields with nearly perfect
      enantioselectivities via dynamic kinetic resolution.

PMID- 22389046
TI  - Noncontact erection is enhanced by Ginkgo biloba treatment in rats: role of
      neuronal NOS in the paraventricular nucleus and sacral spinal cord.
AB  - RATIONALE: Nitric oxide (NO) is an important messenger mediating erection in the
      central nervous system (CNS). Paraventricular nucleus (PVN) neurons can be
      activated by NO and project the signals to the sacral spinal cord, which is
      involved in regulation of erection. Ginkgo biloba extract (EGb 761) facilitates
      noncontact erection (NCE) in rats; however, it is not clear whether EGb 761
      increased NCE is associated with NO. OBJECTIVE: The present study was designed to
      investigate the effects of neuronal nitric oxide synthase (nNOS) on NCE in rats
      following EGb 761 treatment. METHODS: Adult Long-Evans male rats were treated
      with 50 mg/kg of EGb 761 or distilled water for 14 days. The NCE test was
      performed after 14 days of EGb 761 treatment and the NCE frequency was recorded.
      Approximately 14 h following the NCE behavioral tests, animals were sacrificed,
      and nNOS activity in the PVN and S6-L1 spinal cord was measured by
      immunohistochemistry and western blotting, respectively. RESULTS: Treatment with
      50 mg/kg of EGb 761 for 14 days increased the NCE numbers compared to either the
      controls treated with distilled water on the same day or the same group on day 0.
      Also, EGb 761 treatment enhanced nNOS-immunoreactive cell numbers in the PVN.
      Furthermore, western blot analysis showed that EGb 761-treated animals displayed
      higher levels of nNOS expression in the S1 spinal cord than controls. CONCLUSION:
      Our results suggest that enhanced NCE in male rats administrated with EGb 761 may
      be related to the central nNOS activity in the PVN and the spinal cord.

PMID- 22389048
TI  - Longitudinal 1H MRS assessment of the thalamus in a Coriaria lactone-induced
      rhesus monkey status epilepticus model.
AB  - Neurophysiological, biochemical and anatomical evidence implicates the thalamus
      as playing a role in epileptic seizures. Until recently, however, longitudinal
      characterization of in vivo thalamus dynamics had not been reported. In this
      study, we investigated the metabolism in the thalamus to identify the changes
      that occur following Coriaria lactone (CL)-induced status epilepticus (SE) and to
      observe whether the epileptiform discharges could present a difference between
      the left and right thalami. Five rhesus monkeys underwent whole-brain MRI and
      single-voxel MRS on a Siemens Trio Tim 3-T MR scanner with a 12-channel head
      coil. Spectra were processed using LCModel. Scans were performed in five animals
      before SE and at 1, 7, 21 and 42  days after the onset of SE. Statistical
      analysis of the data obtained demonstrated no significant difference in the
      bilateral thalamus of healthy macaques. Our MRS data showed symmetrical
      distributions of N-acetylaspartate in the right and left thalami after SE (p =
      0.003). In addition, this longitudinal study demonstrated elevated
      glutamate/glutamine (p < 0.05) and reduced myo-inositol (p < 0.05) in the
      bilateral thalamus 1  day after SE, and all metabolites approached their baseline
      levels by the fifth scan. Our results demonstrate that metabolic changes occur in
      the thalamus during CL-induced SE in rhesus monkeys. The various metabolic
      changes may indicate that the left thalamus is more vulnerable to epileptic
      strike.

PMID- 22389047
TI  - MU-Opioid receptor availability in the amygdala is associated with smoking for
      negative affect relief.
AB  - RATIONALE: The perception that smoking relieves negative affect contributes to
      smoking persistence. Endogenous opioid neurotransmission, and the MU-opioid
      receptor (MOR) in particular, plays a role in affective regulation and is
      modulated by nicotine. OBJECTIVES: We examined the relationship of MOR binding
      availability in the amygdala to the motivation to smoke for negative affect
      relief and to the acute effects of smoking on affective responses. METHODS:
      Twenty-two smokers were scanned on two separate occasions after overnight
      abstinence using [11C]carfentanil positron emission tomography imaging: after
      smoking a nicotine-containing cigarette and after smoking a denicotinized
      cigarette. Self-reports of smoking motives were collected at baseline, and
      measures of positive and negative affect were collected pre- and post- cigarette
      smoking. RESULTS: Higher MOR availability in the amygdala was associated with
      motivation to smoke to relieve negative affect. However, MOR availability was
      unrelated to changes in affect after smoking either cigarette. CONCLUSIONS:
      Increased MOR availability in amygdala may underlie the motivation to smoke for
      negative affective relief. These results are consistent with previous data
      highlighting the role of MOR neurotransmission in smoking behavior.

PMID- 22389049
TI  - A novel combined radiological method for evaluation of the response to
      chemotherapy for primary bone sarcoma.
AB  - BACKGROUND: In the treatment of bone sarcoma, evaluation of chemotherapeutic
      effects is extremely important. In this study, we compared radiological
      evaluations and histological response, and developed a combined radiological
      scoring system for assessing the response to chemotherapy. METHODS: A total of 79
      patients with primary bone sarcomas were examined by X-ray photography (Xp),
      angiography, MRI, 201Tl scintigraphy (Tl) and 99mTc-MIBI scintigraphy (MIBI) to
      evaluate their response to preoperative chemotherapy. Patients were classified as
      responders and non-responders according to radiological images. All resected
      tumors were evaluated histologically and classified as a good response (>=90%
      necrosis) or a poor response (<=90% necrosis). The sensitivity, specificity,
      accuracy, and kappa values in radiological evaluation were calculated.
      Furthermore, we developed a combined radiological scoring system that correlated
      the results of radiological images with histological response. RESULTS:
      Sensitivity, specificity, and accuracy were 90.9%, 38.2%, and 67.5% (K = 0.31),
      respectively, for Xp; 91.7%, 33.3%, and 66.7% (K = 0.27) for angiography; 81.0%,
      67.6%, and 75.0% (K = 0.49) for MRI; 78.9%, 72.4%, and 76.1% (K = 0.51) for Tl;
      85.3%, 69.2%, and 78.3% (K = 0.55) for MIBI; and 93.3%, 76.5%, and 86.1% (K =
      0.71) for combined radiological scoring. CONCLUSIONS: Combined radiological
      evaluations showed high correlation with histological response for assessing the
      effects of chemotherapy.

PMID- 22389050
TI  - Spin-spin coupling constants in [corrected] artificial DNA intercalated with
      silver cations: theoretical prediction.
AB  - The indirect nuclear spin-spin coupling constants of Ag(+) cation intercalated
      between imidazole rings in DNA chains are calculated by means of DFT with
      relativistic effects taken into account by the use of the zeroth-order regular
      approximation Hamiltonian (DFT-ZORA). The calculations model how the
      (1)J((15)N,(109)Ag) coupling constant is affected by different types of geometry
      deformations and by the presence of water, which is simulated by means of the
      polarizable continuum model and explicitly present water molecules. Calculations
      for systems containing two and three imidazole pairs are also carried out to
      model the influence of stacking interactions. The computed (1)J((15)N,(109)Ag)
      spin-spin coupling constant is in the range of 85-105 Hz (depending on the
      computational model) and is in good agreement with the experimental value (ca. 92
      Hz). This coupling constant is very little affected by the presence of solvent,
      stacking interactions, and geometry deformations. Such behavior is explained by
      visualization of the coupling path by means of coupling energy density (CED).
      Bigger models allow the coupling constant between two adjacent silver ions to be
      computed, and give a value of approximately 1 Hz, which is probably too small to
      be of practical interest. The (2)J((15)N,(15)N) value is calculated to be about
      2.5 Hz, and is therefore of measurable magnitude.

PMID- 22389051
TI  - 23Na double-rotation NMR of sodium nucleotides leads to the discovery of a new
      dCMP hendecahydrate.
AB  - Obtaining definitive information concerning the coordination environment of
      sodium ions which balance the negative charges found in nucleotides is a
      challenging task. We show that high resolution 1D and 2D (23)Na NMR spectra of
      sodium nucleotides obtained in the solid state with the use of double-rotation
      (DOR) provide valuable structural information. Sensitive spin diffusion
      homonuclear correlation experiments are used to establish the relative
      proximities of various pairs of crystallographically distinct Na sites and to
      assign the spectral resonances. Additionally, the DOR sidebands are simulated to
      obtain coordination information which is complementary to that obtained using
      multiple-quantum magic-angle spinning NMR spectra. These experiments led us to
      discover a new hendecahydrate of deoxycytidine monophosphate (dCMP), the
      structure of which is confirmed via single-crystal X-ray diffraction. This
      hydrate crystallizes reproducibly when deuterated water is used exclusively in
      the preparation process.

PMID- 22389052
TI  - Antithrombotic therapy for stroke prevention in atrial fibrillation and
      mechanical heart valves.
AB  - Cardioembolic strokes account for one-sixth of all strokes and are an important
      potentially preventable cause of morbidity and mortality. Vitamin K antagonists
      (e.g., warfarin) are effective for the prevention of cardioembolic stroke in
      patients with atrial fibrillation (AF) and in those with mechanical heart valves
      but because of their inherent limitations are underutilized and often
      suboptimally managed. Antiplatelet therapies have been the only alternatives to
      warfarin for stroke prevention in AF but although they are safer and more
      convenient they are much less efficacious. The advent of new oral anticoagulant
      drugs offers the potential to reduce the burden of cardioembolic stroke by
      providing access to effective, safe, and more convenient therapies. New oral
      anticoagulants have begun to replace warfarin for stroke prevention in some
      patients with AF, based on the favorable results of recently completed phase III
      randomized controlled trials, and provide for the first time an alternative to
      antiplatelet therapy for patients deemed unsuitable for warfarin. The promise of
      the new oral anticoagulants in patients with mechanical heart valves is currently
      being tested in a phase II trial. If efficacy and safety are demonstrated, the
      new oral anticoagulants will provide an alternative to warfarin for patients with
      mechanical heart valves and may also lead to increased use of mechanical valves
      for patients who would not have received them in the past because of the
      requirement for long term warfarin therapy.

PMID- 22389053
TI  - Metal-free synthesis of allylic amines by cross-dehydrogenative-coupling of 1,3
      diarylpropenes with anilines and amides under mild conditions.
AB  - Dehydrogenative cross-coupling reaction of primary anilines, secondary anilines,
      carboxamides, and sulfonamides with 1,3-diarylpropenes to form a series of
      allylic amines promoted by DDQ have been realized. Both monoallylation and
      diallylation products can be selectively synthesized when primary anilines are
      used as the starting materials. The method may provide a wide scope of
      allylamines in scientific research including biologically active compound library
      construction.

PMID- 22389054
TI  - Carnosine and its (S)-TroloxTM derivative protect animals against oxidative
      stress.
AB  - The novel synthetic derivative of carnosine, (S)-6-hydroxy-2,5,7,8
      tetramethylchroman-2-carbonyl-beta-alanyl-L-histidine (S-TroloxTM-Carnosine, STC)
      increases the resistance of rats to experimental acute hypobaric hypoxia (AHH)
      thus protecting brain from the oxidative damage. This effect is accompanied by
      better preservation of the acquired skills in Morris water maze possibly by
      increasing efficiency of the brain antioxidant system. In addition, STC caused an
      increase in life span of both male and female fruit fly Drosophila melanogaster
      whereas carnosine increased life span only in male fruit flies. The results
      indicate that development of the drug based on STC could be beneficial in
      neurology and gerontology.

PMID- 22389056
TI  - Anti-inflammatory effect of piperine in adjuvant-induced arthritic rats--a
      biochemical approach.
AB  - The present study was undertaken to investigate the anti-inflammatory effect of
      piperine against adjuvant-induced arthritis in rats, an experimental model for
      rheumatoid arthritis and compared it with that of the non-steroidal anti
      inflammatory drug indomethacin. Administration of heat-killed Mycobacterium
      tuberculosis (0. 1 ml) intradermally into the right hind paw of rats resulted in
      increased paw volume, lysosomal enzymes, glycoproteins and tissue marker enzymes
      and decreased body weight. However, these changes were reverted to near normal
      levels upon piperine (30 mg/kg body weight, i.p.) treatment. Histopathological
      analysis of joints also revealed that synovial hyperplasia and mononuclear
      infiltration observed in arthritic rats were alleviated by piperine. Thus, the
      present study clearly indicated that piperine possesses promising anti
      inflammatory effect against adjuvant-induced arthritis by suppressing
      inflammation and cartilage destruction.

PMID- 22389055
TI  - Pioglitazone, PPARgamma agonist, attenuates experimental autoimmune neuritis.
AB  - Recent advances demonstrate peroxisome proliferator-activated receptors gamma
      (PPARgamma) agonist, pioglitazone, as an anti-inflammatory drug. We investigated
      the effect of pioglitazone on experimental autoimmune neuritis (EAN) rats.
      Pioglitazone was given once daily (10 mg/kg) by oral gavage feeding from day 1-24
      (suppressive group) and day 11-24 (therapeutic group). Pioglitazone ameliorated
      the clinical score of EAN, decreased expression of TNF-alpha, IFN-gamma, and the
      activation of NF-kappaB, while increasing the expression of PPARgamma and IL-4.
      Furthermore, we observed higher expression of PPARgamma and IL-4 and lower
      expression of TNF-alpha, IFN-gamma and reduced activation of NF-kappaB in
      suppressive group than those in the therapeutic group, which corresponds to lower
      clinical score and earlier disease recovery. Our data effectively demonstrate the
      anti-inflammatory properties of pioglitazone in EAN by inhibition of NF-kappaB
      signaling pathway.

PMID- 22389057
TI  - Two- and four-year-olds learn to adapt referring expressions to context: effects
      of distracters and feedback on referential communication.
AB  - Children often refer to things ambiguously but learn not to from responding to
      clarification requests. We review and explore this learning process here. In
      Study 1, eighty-four 2- and 4-year-olds were tested for their ability to request
      stickers from either (a) a small array with one dissimilar distracter or (b) a
      large array containing similar distracters. When children made ambiguous
      requests, they received either general feedback or specific questions about which
      of two options they wanted. With training, children learned to produce more
      complex object descriptions and did so faster in the specific feedback condition.
      They also tended to provide more information when requesting stickers from large
      arrays. In Study 2, we varied only distracter similarity during training and then
      varied array size in a generalization test. Children found it harder to learn in
      this case. In the generalization test, 4-year-olds were more likely to provide
      information (a) when it was needed because distracters were similar to the target
      and (b) when the array size was greater (regardless of need for information). We
      discuss how clear cues to potential ambiguity are needed for children to learn to
      tailor their referring expression to context and how several cues of heuristic
      value (e.g., more distracters > say more) can promote the efficiency of
      communication while language is developing. Finally, we consider whether it would
      be worthwhile drawing on the human learning process when developing algorithms
      for the production of referring expressions.

PMID- 22389058
TI  - Structure of sodiated polyglycines.
AB  - The intrinsic folding of peptides about a sodium ion has been investigated in
      detail by using infrared multiple photon dissociation (IRMPD) spectroscopy and a
      combination of theoretical methods. IRMPD spectroscopy was carried out on
      sodiated polyglycines G(n)-Na(+) (n=2-8), in both the fingerprint and N-H/O-H
      stretching regions. Interplay between experimental and computational approaches
      (classical and quantum) enables us to decipher most structural details. The most
      stable structures of the small peptides up to G(6)-Na(+) maximize metal-peptide
      interactions with all peptidic C=O groups bound to sodium. In addition, direct
      interactions between peptide termini are possible for G(6)-Na(+) and larger
      polyglycines. The increased flexibility of larger peptides leads to more complex
      folding and internal peptide structuration through gamma or beta turns. A
      structural transition is found to occur between G(6)-Na(+) and G(7)-Na(+),
      leading to a structure with sodium coordination that becomes tri-dimensional for
      the latter. This transition was confirmed by H/D exchange experiments on G(n)
      Na(+) (n=3-8). The most favorable hydrogen-bonding pattern in G(8)-Na(+) involves
      direct interactions between the peptide termini and opens the way to salt-bridge
      formation; however, there is only good agreement between experimental and
      computational data over the entire spectral range for the charge solvation
      isomer.

PMID- 22389059
TI  - Hyperplastic oral candidiasis of the tongue.

PMID- 22389060
TI  - Transient amnesia: epileptic or global? A differential diagnosis with significant
      implications for management.

PMID- 22389061
TI  - Improved motion correction capabilities for fast spin echo T1 FLAIR propeller
      using non-cartesian external calibration data driven parallel imaging.
AB  - Patient motion is a common challenge in the clinical setting and fast spin echo
      longitudinal relaxation time fluid attenuating inversion recovery imaging method
      with motion correction would be highly desirable. The motion correction provided
      by transverse relaxation time- and diffusion-weighted periodically rotated
      overlapping parallel lines with enhanced reconstruction methods has seen
      significant clinical adoption. However, periodically rotated overlapping parallel
      lines with enhanced reconstruction with fast spin echo longitudinal relaxation
      time fluid attenuating inversion recovery-weighting has proved challenging since
      motion correction requires wide blades that are difficult to acquire while also
      maintaining short echo train lengths that are optimal for longitudinal relaxation
      time fluid attenuating inversion recovery-weighting. Parallel imaging provides an
      opportunity to increase the effective blade width for a given echo train lengths.
      Coil-by-coil data-driven autocalibrated parallel imaging methods provide greater
      robustness in the event of motion compared to techniques relying on accurate coil
      sensitivity maps. However, conventional internally calibrated data-driven
      parallel imaging methods limit the effective acceleration possible for each
      blade. We present a method to share a single calibration dataset over all imaging
      blades on a slice by slice basis using the APPEAR non-cartesian parallel imaging
      method providing an effective blade width increase of 2.45*, enabling robust
      motion correction. Results comparing the proposed technique to conventional
      cartesian and periodically rotated overlapping parallel lines with enhanced
      reconstruction methods demonstrate a significant improvement during subject
      motion and maintaining high image quality when no motion is present in normal and
      clinical volunteers.

PMID- 22389062
TI  - The emerging role of Arf/Arl small GTPases in cilia and ciliopathies.
AB  - Once overlooked as an evolutionary vestige, the primary cilium has recently been
      the focus of intensive studies. Mounting data show that this organelle is a hub
      for various signaling pathways during vertebrate embryonic development and
      pattern formation. However, how cilia form and how cilia execute the sensory
      function still remain poorly understood. Cilia dysfunction is correlated with a
      wide spectrum of human diseases, now termed ciliopathies. Various small GTPases,
      including the members in Arf/Arl, Rab, and Ran subfamilies, have been implicated
      in cilia formation and/or function. Here we review and discuss the role of one
      particular group of small GTPase, Arf/Arl, in the context of cilia and
      ciliopathy.

PMID- 22389063
TI  - Percutaneous cerclage wiring and minimally invasive plate osteosynthesis (MIPO):
      a percutaneous reduction technique in the treatment of Vancouver type B1
      periprosthetic femoral shaft fractures.
AB  - BACKGROUND: Periprosthetic femoral fractures (PPFs) associated at or near a well
      fixed femoral prostheses (Vancouver type-B1) present a clinical challenge due to
      the quality of the bone stock and instability of the fracture. OBJECTIVES: The
      purpose of this study was to present a novel reduction technique and analyze
      clinical and radiographic outcome in patients with Vancouver type-B1 fractures
      treated with percutaneous cerclage wiring for fracture reduction and maintenance
      of reduction with minimally invasive plate osteosynthesis (MIPO) utilizing a
      locking compression plate (LCP). METHODS: Between March 2007 and December 2008,
      ten consecutive patients with spiral, oblique or wedge Vancouver type-B1 were
      treated with closed percutaneous cerclage wiring using a new cerclage passer
      instrument (Synthes) through small 2-3 cm incisions for reduction and maintenance
      of reduction. Internal fixation with MIPO was obtained utilizing a long LCP
      Synthes bridging the fracture. The reduction time, fixation time and operative
      time were recorded. The rehabilitation protocol consisted of partial weight
      bearing as tolerated. Clinical and radiographic outcomes included evidence of
      union, return to pre-injury mobility, and surgical complications were recorded.
      RESULTS: There were three men and seven women with an average age of 74 years
      (range 47-84 years) at the time the fracture occured. The average follow-up was
      13.2 months. One patient died 2 months after surgery due to cardiovascular
      problems and was excluded. The average reduction time with percutaneous cerclage
      wiring was 24.4 min (range 7-45 min). The average fixation time was 79 min (range
      53-100 min). The average operative time was 103 min (range 75-140 min). Blood
      loss was minimal and only two patients needed a blood transfusion. All fractures
      healed with a mean time to union of 18 weeks (range 16-20 weeks). There was one
      implant which bent 10 degrees  in the post-operative period but went on to heal
      uneventfully within 16 weeks. There was no evidence of loosening of any implants.
      Seven patients returned to their previous level of mobility. Two patients
      required a walker. There were no implant failures, wound complications or
      infections. CONCLUSIONS: Percutaneous reduction of spiral, oblique or wedge-type
      B1 PPFs with percutaneous cerclage wiring combined with minimally invasive
      locking plate osteosynthesis provided satisfactory reduction, adequate stability
      and healing in nine patients. Our early results suggest that this reduction
      technique and fixation may be a useful solution for this growing challenge in
      orthopaedics. The authors caution that this technique must be done carefully to
      avoid serious complications, e.g., vascular injury.

PMID- 22389064
TI  - Staging laparoscopy using ALA-mediated photodynamic diagnosis improves the
      detection of peritoneal metastases in advanced gastric cancer.
AB  - BACKGROUND: This study evaluated the usefulness of photodynamic diagnosis (PDD)
      using oral 5-aminolevulinic acid (ALA) for the detection of peritoneal metastases
      in advanced gastric cancer. METHOD: First, the numbers of peritoneal metastatic
      nodules that were visible under conventional white light (WL) and ALA-induced
      fluorescence (ALA-F) were quantified in a mouse model of peritoneal metastasis to
      compare the tumor detection rate. Next, staging laparoscopy (SL) using ALA-PDD
      was performed in 13 advanced gastric cancer patients with serosa-invading tumors,
      and the detection sensitivity of ALA-PDD was compared to the observations using
      WL. RESULTS: The tumor detection rate using ALA-F was significantly higher than
      the detection rate using WL (72% vs. 39%, respectively, P < 0.0001). Peritoneal
      metastases were detected in five patients using SL with ALA-PDD, and liver
      metastases were detected in one patient. These metastases were confirmed using
      histological examination. Three metastatic lesions that were invisible under WL
      were detected under ALA-F. CONCLUSION: This study demonstrated that SL with ALA
      PDD improved the detection sensitivity for peritoneal metastases. ALA-PDD may be
      an important technique for the preoperative staging of advanced gastric cancer,
      and ALA-PDD will provide useful information for the selection of therapeutic
      modality.

PMID- 22389065
TI  - Ambient rutile VO2(R) hollow hierarchitectures with rich grain boundaries from
      new-state nsutite-type VO2, displaying enhanced hydrogen adsorption behavior.
AB  - Modulating the interaction between small gas molecules and solid host materials
      is becoming increasingly important for the future society due to the alternative
      energy resources especially for the hydrogen energy. As is known, two catalogues
      of materials such as two-dimensional (2D) lamellar cavity structures and three
      dimensional (3D) infinite tunnel structures have received intensive
      considerations during the past decades. Herein, we put forward a new alternative
      that the solid materials with synergic effects of grain-boundary-rich (GBR)
      structure and 3D hierarchical hollow structure would also be a promising
      candidate for modulating the gas molecules in solid adsorbents. As expected, our
      constructed novel 3D hollow hierarchitectures with GBR shells standing on the
      hollow spherical cavity indeed resulted in the enhanced hydrogen adsorption
      behavior. The as-prepared 3D hollow hierarchitectures were very uniform in large
      scale, and the very simple reaction process offers high convenience, short
      reaction time, and no need for any complex manipulations or equipments. The
      hollow outlook of the rutile VO(2)(R) 3D hierarchitectures is the reminiscence of
      the hollow cavity of nsutite-type VO(2), while the formation of the VO(2)(R) GBR
      structure is attributed to volume shrink from a unique intergrowth structure of
      nsutite-type VO(2). The novel gas modulation model with the synergic effect of
      GBR structure and hierarchical hollow structure may pave a new way for developing
      materials in energy and environmental fields in the near future.

PMID- 22389066
TI  - Intracrystalline diffusion in mesoporous zeolites.
AB  - Specially synthesized extra-large crystallites of zeolite LTA with intentionally
      added mesoporosity are used for an in-depth study of guest diffusion in
      hierarchical nanoporous materials by the pulsed field gradient NMR technique.
      Using propane as a guest molecule, intracrystalline mass transfer is demonstrated
      to be adequately described by a single effective diffusivity resulting from the
      weighted average of the diffusivities in the two (micro- and meso-) pore spaces.
      Gas-kinetic order-of-magnitude estimates of the diffusivities are in satisfactory
      agreement with the experimental data and are thus shown to provide a
      straightforward means for predicting and quantifying the benefit of
      hierarchically structured nanoporous materials in comparison with their purely
      microporous equivalent.

PMID- 22389068
TI  - A novel mutation in MPL (Y252H) results in increased thrombopoietin sensitivity
      in essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is a rare type of myeloproliferative neoplasm
      characterized by clonal expansion of the megakaryocyte and platelet lineage.
      Here, we describe a novel mutation (Y252H) in the thrombopoietin (TPO) receptor,
      or MPL, in a JAK2 mutation-negative ET patient. The bone marrow examination
      revealed increased numbers of dysmorphic megakaryocytes with focal clustering.
      The x-inactivation pattern suggested clonal expansion of hematopoietic cells in
      the bone marrow. Furthermore, we found that the patient's bone marrow cells were
      hypersensitive to TPO in generating megakaryocyte colonies in vitro. More
      importantly, we demonstrated that this MPL Y252H mutant confers increased TPO/MPL
      mediated cell growth and increased cell survival upon cytokine withdrawal in BaF3
      cells, indicating it is a disease-driving mutation and may contribute to the
      development of ET in vivo. In summary, this is the first report describing a
      mutation in the extracellular domain of MPL underlying ET.

PMID- 22389069
TI  - Immune attributes of cardiac-derived adherent proliferating (CAP) cells in
      cardiac therapy.
AB  - Cardiac-directed cell therapies show potential to reduce mortality and morbidity
      in heart disease. However, high functional efficacy should be complimented with
      low immunogenicity, in particular if allogeneic cell sources are applied.
      Therefore, we aimed to examine cardiac-derived adherent proliferating (CAP) cells
      with respect to their immunogenicity and immune modulatory features in vitro.
      Human CAP cells were isolated from cardiac biopsies and screened in a CFSE-based
      proliferation assay in co-cultures with phytohaemagglutinin (PHA)-stimulated
      human peripheral blood lymphocytes (PBMCs) or mixed lymphocyte cultures (MLCs) to
      assess their potential to induce immune cell proliferation or activation by flow
      cytometry. Moreover, levels of pro- and anti-inflammatory cytokines in
      supernatants of co-cultures were analysed. The capacity of CAP cells to induce
      the generation of regulatory T cells (Tregs) was determined by flow cytometric
      measurement of FoxP3 expression. CAP cells of different donors (n = 5) showed low
      immunogenicity in co-cultures with human allogeneic PBMCs. In addition, they
      induced no change in the normal alloantigen-driven immune responsiveness in MLCs.
      However, CAP cells significantly reduced the induction of immune cell
      proliferation in PBMCs cultures stimulated with the polyclonal trigger PHA.
      Adding CAP cells into MLCs or PHA-stimulated cultures resulted in significantly
      reduced levels of TNFalpha or IFNgamma, respectively, compared to controls
      without CAP cells. At early time points (day 2), interaction of CAP cells with
      PBMCs resulted in elevated proportions of FoxP3+ CD4+ CD25(high+) cells. The
      results indicate that CAP cells have low immunogenicity and could be advantageous
      in cardiac repair by reducing inflammatory cytokines and inducing regulatory T
      cells.

PMID- 22389070
TI  - Recent progress in the application of atomic force microscopy for supported lipid
      bilayers.
AB  - In the past two decades, atomic force microscopy has been widely used for
      studying supported lipid bilayer related research, including the structure and
      dynamics of membranes and membrane proteins, and the interaction of membranes
      with chemical and biological molecules. The focus of this minireview is on the
      recent progress in the application of atomic force microscopy for supported lipid
      bilayers. Such progress mainly includes the application in the following aspects:
      submolecular-resolution imaging, in situ observation, and nanomechanics
      measurement.

PMID- 22389071
TI  - Evidence for a specific impairment of serial order short-term memory in dyslexic
      children.
AB  - In order to better understand the nature of verbal short-term memory (STM)
      deficits in dyslexic children, the present study used the distinction between
      item and serial order retention capacities in STM tasks. According to recent STM
      models, storage of verbal item information depends very directly upon the
      richness of underlying phonological and semantic representations. On the other
      hand, storage of serial order information appears to reflect a language
      independent system. Hence, if there is a fundamental STM deficit in dyslexia that
      is not to be explained only by the poor phonological processing abilities that
      characterize dyslexia, then difficulties in serial order STM should also be
      observed in dyslexic children. We administered tasks maximizing either serial
      order or item retention capacities to dyslexic children and reading age (RA) and
      chronological age (CA) matched controls. Dyslexic children performed
      significantly poorer than the CA controls on the item STM measure. Furthermore,
      the dyslexic group obtained inferior performance than both CA and RA control
      groups on the serial order STM measure. These findings highlight a severe
      impairment of STM for serial order information in dyslexia that cannot be reduced
      to a phonological processing impairment. Implications of serial order retention
      deficits for reading acquisition and dyslexia are discussed.

PMID- 22389072
TI  - A model for cellulase production from Trichoderma reesei in an airlift reactor.
AB  - A mathematical model for cellulase production by Trichoderma reesei RUT-C30 grown
      in a cellulose medium with lactose as fed batch in an airlift reactor is
      proposed. To describe adequately the mass transfer between the air bubbles and
      the broth, it uses computational fluid dynamics (CFD) including multiphase
      Eulerian-Eulerian formulation, with a detailed description of the bubble size
      distribution through the use of the population balance model (PBM) and the class
      method (CM). The kinetics of the biomass growth is further coupled to the fluid
      flow conditions using partial differential equations for all the species
      involved, providing detailed information of important reactor conditions such as
      the distribution of oxygen, cellulose, and the shear stress within the reactor
      over the entire period of fermentation. Predicted results agree well with the
      available overall measurements for a typical fed-batch operation and detailed
      profiles of the predicted concentration fields are discussed from an engineering
      viewpoint.

PMID- 22389074
TI  - Applied human psychopharmacology: the practical psychobiological consequences of
      some novel and ancient psychoactive drugs.

PMID- 22389073
TI  - Herniamed: an internet-based registry for outcome research in hernia surgery.
AB  - PURPOSE: Despite the high frequency of hernia surgery procedures and continuous
      improvements, thanks to new hernia meshes and fixation techniques, in Germany,
      for example, the recurrence rate and rate of chronic inguinal pain after inguinal
      surgery are more than 10% far too high. Introduction of a hernia register in
      Denmark led to a significant reduction in the recurrence rate. METHODS: The aim
      of a hernia registry as an application-oriented outcome research tool is to
      monitor and evaluate (concomitant research) how the knowledge gleaned from
      evidence-based science is implemented in the everyday clinical setting and,
      ultimately, investigate its effectiveness (outcome research). RESULTS: The new
      Internet-based English- and German-language registry for the entire spectrum of
      inpatient and outpatient hernia surgery is designed to improve the quality of
      patient care and provide valid data on outcome research. Via the Internet, all
      relevant patient data (comorbidities, previous operations, staging, specific
      surgical technique, medical devices used, perioperative complications and follow
      up data) can be entered into the registry database. The participating hospitals
      and surgeons can at any time view their own data by means of an evaluation
      statistics tool. The outcome research project Herniamed focuses on inguinal
      hernias, umbilical hernias, incisional hernias, epigastric hernias, parastomal
      hernias and hiatus hernias. The online-based outcome research registry meets the
      most stringent data protection criteria. CONCLUSION: With the Internet-based
      English- and German-language hernia register, a new instrument is now available
      for outcome research in hernia surgery.

PMID- 22389075
TI  - 5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'.
AB  - OBJECTIVES: The fully synthetic 'legal high' 5,6-methylenedioxy-2-aminoindane
      (MDAI) is an analogue of 3,4-methylenedioxymethamphetamine. Although developed in
      the 1990s, it was not widely abused until 2010. However, mephedrone was banned in
      the UK in April 2010, and almost immediately, MDAI was widely advertised as a
      legal alternative. This paper provides both an overview of the current state of
      knowledge of MDAI and a critical analysis of online available information
      relating to its psychoactive effects, adverse reactions and use in combination
      with other drugs. METHODS: The literature on MDAI was searched in three
      databases: PsycInfo, PubMed and MedScape. Once the availability of information on
      MDAI was identified within these websites, further specific searches were carried
      out for narratives focusing on the nature of its effects on users, motivations
      behind its recreational use and possible trends of misuse, and any other relevant
      information. RESULTS: Internet-sourced products have been shown variously to
      contain mephedrone, and mixed compositions of inorganic substances, while
      containing no MDAI. Numbers of Internet searches have been considerably higher in
      the UK compared with Germany and the US. CONCLUSIONS: Better international
      collaboration levels may be needed to tackle the novel and fast growing
      phenomenon of novel psychoactive drug availability from the web.

PMID- 22389076
TI  - The effects of 'ecstasy' (MDMA) on visuospatial memory performance: findings from
      a systematic review with meta-analyses.
AB  - To review, with meta-analyses where appropriate, performance differences between
      ecstasy (3,4-methylenedioxymethamphetamine) users and non-users on a wider range
      of visuospatial tasks than previously reviewed. Such tasks have been shown to
      draw upon working memory executive resources. Abstract databases were searched
      using the United Kingdom National Health Service Evidence Health Information
      Resource. Inclusion criteria were publication in English language peer-reviewed
      journals and the reporting of new findings regarding human ecstasy-users'
      performance on visuospatial tasks. Data extracted included specific task
      requirements to provide a basis for meta-analyses for categories of tasks with
      similar requirements. Fifty-two studies were identified for review, although not
      all were suitable for meta-analysis. Significant weighted mean effect sizes
      indicating poorer performance by ecstasy users compared with matched controls
      were found for tasks requiring recall of spatial stimulus elements, recognition
      of figures and production/reproduction of figures. There was no evidence of a
      linear relationship between estimated ecstasy consumption and effect sizes. Given
      the networked nature of processing for spatial and non-spatial visual
      information, future scanning and imaging studies should focus on brain activation
      differences between ecstasy users and non-users in the context of specific tasks
      to facilitate identification of loci of potentially compromised activity in
      users.

PMID- 22389077
TI  - The effect of d-methamphetamine on simulated driving performance.
AB  - OBJECTIVES: Methamphetamine is considered to be one of the most popularly abused
      drugs by drivers; however, its exact effect on driving and driving behaviour has
      yet to be thoroughly investigated. This being despite methamphetamine's increased
      prevalence in injured and deceased drivers. METHODS: Twenty healthy recreational
      illicit stimulant users (10 male and 10 female), aged between 21 and 32 years
      (mean = 25.4 years, SD = 3.3 years) attended two testing sessions involving oral
      consumption of 0.42 mg/kg d-methamphetamine or a matching placebo. The drug
      administration was counter-balanced, double-blind, and medically supervised. At
      each session driving, performance was assessed 2.5 h post drug administration.
      RESULTS: d-methamphetamine (0.42 mg/kg) did not significantly impair overall
      simulated driving performance 2.5 h post drug administration. At the individual
      driving variable level, participants in the d-methamphetamine condition were
      observed to be driving slower when an emergency situation occurred (T = 44, p <
      0.05), but interestingly, participants in both conditions recorded average speeds
      in excess of the speed limit (100 km/h) when the emergency situations occurred.
      The d-methamphetamine condition did also produce four times more infringements
      where participants did not stop at red traffic light in comparison to the
      placebo, but this effect was only evident at a trend level (T = 7, p = 0.11).
      CONCLUSIONS: The findings presented herein suggest that d-methamphetamine
      administered at the levels supplied did not impair driving performance in a
      manner consistent with epidemiological evidence. Further research is certainly
      required to elucidate the effects of various doses of methamphetamine, alone and
      in combination with other legal and illicit substances.

PMID- 22389078
TI  - Phenomenon of new drugs on the Internet: the case of ketamine derivative
      methoxetamine.
AB  - On the basis of the material available both in the scientific literature and on
      the web, this paper aims to provide a pharmacological, chemical and behavioural
      overview of the novel compound methoxetamine. This is a dissociative drug related
      to ketamine, with a much longer duration of action and intensity of effects. A
      critical discussion of the availability of information on the web of
      methoxetamine as a new recreational trend is here provided. Those methodological
      limitations, which are intrinsically associated with the analysis of online, non
      peer reviewed, material, are here discussed as well. It is concluded that the
      online availability of information on novel psychoactive drugs, such as
      methoxethanine, may constitute a pressing public health challenge. Better
      international collaboration levels and novel forms of intervention are necessary
      to tackle this fast-growing phenomenon.

PMID- 22389079
TI  - Explaining the stress-inducing effects of nicotine to cigarette smokers.
AB  - AIMS: To explain how nicotine dependency causes mood fluctuation and increases
      daily stress. METHODS: Prospective studies show that taking-up smoking leads to
      higher stress and depression. Cross-sectional studies show that adult smokers
      report more irritability, stress and depression than non-smokers. Prospective
      studies show that smoking cessation leads to enduring mood gains. The adverse
      mood effects of nicotine dependency are explained by the deprivation reversal
      model. In between cigarettes, most smokers experience subtle abstinence symptoms,
      and cumulatively these can increase everyday stress. Hence, adolescents who take
      up smoking become more stressed, and quitting reduces stress. An explanatory
      leaflet to explain this model was empirically assessed with tobacco smokers.
      RESULTS: In a cohort study of 82 cigarette smokers, knowledge levels were
      significantly enhanced by the explanatory leaflet, and this understanding was
      maintained 1 week later. Hence, normal cigarette smokers can understand the
      adverse mood consequences of nicotine addiction. The information leaflet could
      prove useful for tobacco-education packages in schools, and smoking-cessation
      packages with adults. CONCLUSIONS: The deprivation reversal model can be easily
      described using a simple leaflet. It explains how nicotine dependency can cause
      mood fluctuation, and outlines the psychological benefits of quitting.

PMID- 22389081
TI  - The effects of multitasking on psychological stress reactivity in recreational
      users of cannabis and MDMA.
AB  - BACKGROUND: Cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use is
      associated with psychobiological and neurocognitive deficits. Assessments of the
      latter typically include tests of memory and everyday cognitive functioning.
      However, to date, little attention has been paid to effects of drug use on
      psychological stress reactivity. We report three studies examining the effects of
      recreational use of cannabis and MDMA on mood and psychological responses to
      multitasking using a cognitively demanding laboratory stressor that provides an
      analogue for everyday situations involving responses to multiple stimuli.
      METHODS: The effects of the multitasking framework on mood and perceived workload
      were assessed in cannabis (N=25), younger (N=18) and older (N=20) MDMA users and
      compared with non-target drug controls. RESULTS: Compared with respective control
      groups, cannabis users became less alert and content, and both MDMA groups became
      less calm following acute stress. Unexpectedly, the stressor increased ratings of
      calm in cannabis users. Users also scored higher than their controls with respect
      to ratings of resources needed to complete the multitasking framework.
      CONCLUSIONS: These findings show, for the first time, that recreational use of
      cannabis and MDMA, beyond the period of intoxication, can negatively influence
      psychological responses to a multitasking stressor, and this may have
      implications for real-life situations which place high demands on cognitive
      resources.

PMID- 22389082
TI  - Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance
      and mood in healthy humans: a double-blind, placebo-controlled, crossover
      investigation.
AB  - OBJECTIVE: The aim of the study was to assess the effects of oral ingestion of
      the 'green tea' polyphenol epigallocatechin gallate (EGCG) on cognitive
      performance, mood and localised cerebral blood flow (CBF) parameters in healthy
      human adults. METHOD: In this double-blind, placebo-controlled, crossover study,
      27 healthy adults received placebo and two doses (135 and 270 mg) of EGCG in
      counterbalanced order on separate days. Following a 45-min resting absorption
      period, participants performed a selection of computerised cognitive tasks that
      activate the frontal cortex for a further 42 min. CBF and haemodynamics, as
      indexed by concentration changes in oxygenated and deoxygenated haemoglobin, were
      assessed in the frontal cortex throughout the post-treatment period using Near
      infrared spectroscopy (NIRS). RESULTS: During the post-dose task performance
      period, the administration of 135 mg EGCG resulted in reduced CBF in the frontal
      cortex, as indexed by significantly lower concentrations of both oxygenated and
      total haemoglobin, in comparison with placebo. Heart rate was significantly
      reduced from pre dose to post dose across all treatments. No significant
      differences were observed for the level of deoxygenated haemoglobin or on any of
      the cognitive performance/mood measures. CONCLUSIONS: These results demonstrate
      that a single dose of orally administered EGCG can modulate CBF parameters in
      healthy humans but that this is not associated with changes in cognitive
      performance or mood.

PMID- 22389080
TI  - Immune system inflammation in cocaine dependent individuals: implications for
      medications development.
AB  - OBJECTIVES: Cocaine dependence is a chronic stress state. Furthermore, both
      stress and substance abuse have robust and reciprocal effects on immune system
      cytokines, which are known to be powerful modulators of mood. We therefore
      examine basal and provoked changes in peripheral cytokines in cocaine dependent
      individuals to better understand their role in the negative reinforcing effects
      of cocaine. METHODS: Twenty-eight (16 F/12 M) treatment-seeking cocaine dependent
      individuals and 27 (14 F/13 M) social drinkers were exposed to three 5-min guided
      imagery conditions (stress, drug cue, relaxing) presented randomly across
      consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha
      (TNFalpha), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL
      1ra) were collected at baseline and various post-imagery time-points. RESULTS:
      Cocaine abusers demonstrated decreased basal IL-10 compared with social drinkers.
      They also showed significant elevations in pro-inflammatory TNFalpha when exposed
      to stress compared with when they were exposed to relaxing imagery. This was not
      observed in the social drinkers. Conversely, social drinkers demonstrated
      increases in the anti-inflammatory markers, IL-10 and IL-1ra, following exposure
      to cue, which were not seen in the dependent individuals. CONCLUSIONS: Cocaine
      dependent individuals demonstrate an elevated inflammatory state both at baseline
      and following exposure to the stress imagery condition. Cytokines may reflect
      potentially novel biomarkers in addicted populations for treatment development.

PMID- 22389083
TI  - The effects of heavy social drinking on executive function: a systematic review
      and meta-analytic study of existing literature and new empirical findings.
AB  - BACKGROUND: Previous investigations of executive function in alcohol dependent
      and in social drinkers have not always produced consistent results and have not
      utilised key indicators of recent theoretical models of Executive Function (EF).
      The present paper reports the results of two studies that seek to address these
      limitations. METHOD: Study 1 took the form of a systematic review and meta
      analysis of studies examining EF in social drinkers. In Study 2, 41 participants
      completed an alcohol use inventory and were assigned to either light or heavy
      alcohol use via median split of average weekly dose. Participants completed
      measures of the fractionated executive processes of updating, shifting,
      inhibition and access to semantic memory. RESULTS: Study 1 only identified seven
      studies of EF in social drinkers, and the mean effect size was non-significant.
      In study 2, the heavy alcohol use group performed worse on all measures of
      executive functioning except memory updating. CONCLUSIONS: To our knowledge, this
      is the first systematic investigation of executive functioning in social
      drinkers. Given that the participants were non-treatment seeking social drinking
      students, the EF deficit in the heavy user group is particularly worrying and
      could increase the likelihood of developing an alcohol use disorder.

PMID- 22389085
TI  - Adult attention deficit hyperactivity disorder and other psychiatric symptoms in
      recreational polydrug users.
AB  - AIMS: Previous research has shown that recreational drug use is associated with
      more psychiatric symptoms and psychobiological distress. This study investigated
      whether symptoms of adult attention deficit hyperactivity disorder (ADHD) were
      also raised in polydrug users. METHODS: We assessed a non-clinical sample of 84
      unpaid volunteers (mean age 27.5 years): n = 17 light-novice polydrug users; n =
      29 moderate polydrug users; and n = 38 non-user controls (14 non-drug users, 24
      alcohol/tobacco users). They completed the Symptom Checklist 90 (SCL-90) self
      rating inventory for psychiatric symptoms, the Adult ADHD Self-report Scale
      symptom checklist for adult ADHD, and also the questions on positive moods and
      sociability. Saliva samples provided a neuroendocrine cortisol measure. RESULTS:
      Moderate polydrug users reported significantly higher adult ADHD symptoms and SCL
      90 psychiatric symptoms and lower sociability than non-user controls and light
      polydrug users. Novice-light polydrug users did not differ from control groups on
      any measure. There were no significant group differences in cortisol. These
      findings are debated using the interactive diathesis-distress model. Psychoactive
      drugs can affect both mood and cognition. When taken regularly, the drug-induced
      psychobiological vacillation may exacerbate prior problems with mood stability
      and attentional-cognitive control. CONCLUSIONS: It is not polydrug usage per se,
      but rather their regular-repeated usage, that is associated with increased signs
      of psychiatric and attentional-hyperactivity distress.

PMID- 22389084
TI  - Effects of cumulative stress and impulsivity on smoking status.
AB  - OBJECTIVE: The stress-vulnerability model of addiction predicts that
      environmental factors, such as cumulative stress, will result in individual
      adaptations that decrease self-control, increase impulsivity, and increase risk
      for addiction. Impulsivity and cumulative stress are risk factors for tobacco
      smoking that are rarely examined simultaneously in research. METHODS: We examined
      the indirect and direct effects of cumulative adversity in a community sample
      consisting of 291 men and women who participated in an assessment of cumulative
      stress, self-reported impulsivity, and smoking history. Data were analyzed using
      bootstrapping techniques to estimate indirect effects of stress on smoking via
      impulsivity. RESULTS: Cumulative adversity is associated with smoking status via
      direct effects and indirect effects through impulsivity scores. Additional models
      examining specific types of stress indicate contributions of traumatic stress and
      recent life events as well as chronic relationship stressors. CONCLUSIONS:
      Overall, cumulative stress is associated with increased risk of smoking via
      increased impulsivity and via pathways independent of impulsivity. These findings
      support the stress-vulnerability model and highlight the utility of mediation
      models in assessing how, and for whom, cumulative stress increases risk of
      current cigarette smoking. Increasing self-control is a target for interventions
      with individuals who have experienced cumulative adversity.

PMID- 22389086
TI  - Cannabis-related deficits in real-world memory.
AB  - BACKGROUND: Research shows that cannabis users exhibit deficits in prospective
      memory (PM) and executive function, which persist beyond acute intoxication.
      However, many studies rely on self-reports of memory failures or use laboratory
      based measures that may not mimic functional deficits in the real world. The
      present study aimed to assess real-world memory functioning. METHOD: Twenty
      cannabis-only users and 20 non-illicit drug users were recruited. Participants
      completed a substance use inventory and a mood scale, followed by a non-immersive
      virtual reality task assessing PM and executive functioning. The task involved
      the participant playing the role of an office worker for the day and performing
      routine office duties. A number of subscales were used to assess facets of
      executive function (planning, adaptive thinking, creative thinking, selection,
      prioritisation) and PM (time-based, event-based and action-based PM). RESULTS:
      Multivariate analysis of variance revealed cannabis users performed worse overall
      on the task, with poor performance on the planning, time-based PM and event-based
      PM subscales. In addition, indices of cannabis (length, dose, frequency, total
      use) were correlated with performance on these three subscales. CONCLUSIONS: The
      present study expands on previously established research, providing support for
      the cannabis-related deficits in PM and executive functioning, and the role of
      different aspects of cannabis use in these deficits.

PMID- 22389087
TI  - Residual effects of ecstasy (3,4-methylenedioxymethamphetamine) on low level
      visual processes.
AB  - 'Ecstasy' (3,4-methylenedioxymethamphetamine) induces impaired functioning in the
      serotonergic system, including the occipital lobe. This study employed the 'tilt
      aftereffect' paradigm to operationalise the function of orientation-selective
      neurons among ecstasy consumers and controls as a means of investigating the role
      of reduced serotonin on visual orientation processing. The magnitude of the tilt
      aftereffect reflects the extent of lateral inhibition between orientation
      selective neurons and is elicited to both 'real' contours, processed in visual
      cortex area V1, and illusory contours, processed in V2. The magnitude of tilt
      aftereffect to both contour types was examined among 19 ecstasy users (6 ecstasy
      only; 13 ecstasy-plus-cannabis users) and 23 matched controls (9 cannabis-only
      users; 14 drug-naive). Ecstasy users had a significantly greater tilt magnitude
      than non-users for real contours (Hedge's g = 0.63) but not for illusory contours
      (g = 0.20). These findings provide support for literature suggesting that
      residual effects of ecstasy (and reduced serotonin) impairs lateral inhibition
      between orientation-selective neurons in V1, which however suggests that ecstasy
      may not substantially affect this process in V2. Multiple studies have now
      demonstrated ecstasy-related deficits on basic visual functions, including
      orientation and motion processing. Such low-level effects may contribute to the
      impact of ecstasy use on neuropsychological tests of visuospatial function.

PMID- 22389088
TI  - Inflammatory mediators involved in the progression of the metabolic syndrome.
AB  - The metabolic syndrome is often associated with type 2 diabetes mellitus,
      dyslipidemia, atherosclerosis, hypertension, steatosis of the liver and other
      organs, as well as hypertension, type 2 diabetes mellitus, and atherosclerosis.
      Recent studies have implicated a number of inflammatory mediators including
      cytokines, adipokines and eicosanoids in the inflammatory responses that
      accompany the metabolic syndrome. Measurements of the circulating levels of the
      inflammatory molecules that accompany this syndrome might provide leads to
      therapeutic approaches to modulate the inflammatory responses and thereby alter
      disease progression. In this review, we summarize recent studies on classical and
      newer inflammatory mediators in the pathogenesis of the metabolic syndrome in
      humans and experimental models.

PMID- 22389089
TI  - Clinical, histopathologic, and genetic features of pediatric primary
      myelofibrosis--an entity different from adults.
AB  - Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by
      cytopenias, leukoerythroblastosis, extramedullary hematopoiesis,
      hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare
      disorder in adults; children are even less commonly affected by this entity, with
      the largest pediatric case series reporting on three patients. Most literature
      suggests spontaneous resolution of myelofibrosis without long term complications
      in the majority of affected children. We describe the clinical, pathologic, and
      molecular characteristics and outcomes of nineteen children with primary
      myelofibrosis treated in our center from 1984 to 2011. Most patients had
      cytopenia significant enough to require supportive therapy. No child developed
      malignant transformation and only five of the 19 children (26%) had spontaneous
      resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations
      were performed on bone marrow samples from 17 and six patients, respectively, and
      the results were negative. In conclusion, analysis of this large series of
      pediatric patients with primary myelofibrosis demonstrates distinct clinical,
      hematologic, bone marrow, and molecular features from adult patients.

PMID- 22389090
TI  - Development of tissue engineered vascular grafts and application of nanomedicine.
AB  - Vascular Tissue Engineering belongs to a rapidly expanding discipline. Tissue
      engineered vascular grafts (TEVG) have a broad range of clinical application
      extending from use as small diameter vascular grafts in adult peripheral
      vasculature to serving as large vessel conduits in pediatric cardiovascular
      surgery. Several approaches have been utilized by different groups to design
      these grafts. Preliminary outcomes are exceedingly promising. These grafts have
      demonstrated the ability to transform into living blood vessels with growth
      potential and while the underlying mechanisms remain to be elucidated, it has
      been shown that inflammatory pathways may play an important role. Small animal
      experiments, development of cell seeding techniques and the application of
      nanotechnology have all contributed vastly to our understanding of the mechanisms
      involved in TEVG remodeling. The application of nanomedicine in TEVG design
      continues to expand at a rapid rate and has provided some clues as to how
      vascular graft design can be pursued in the future. In this review we discuss the
      current state of the field of tissue engineered vascular grafts and how the
      principles of nanomedicine are being applied to aid in the design of second
      generation grafts.

PMID- 22389091
TI  - Can vaccination against pneumococci prevent otitis media with effusion?
AB  - The most common cause of hearing loss in early childhood is otitis media with
      effusion (OME). Prevention of OME in preschool children will improve quality of
      life. The authors aimed to determine, by the best available published evidence,
      whether vaccination against pneumococci effectively prevents OME. The study
      design was based on systematic review (SR) of randomized controlled trials (Level
      1a evidence). The medical literature available through searching Medline database
      was reviewed using the following keywords "Otitis media with effusion,"
      "secretory otitis media," or "glue ear," and "vaccination" limiting the search to
      randomized controlled trials (RCTs) conducted on children (0-18 years), published
      in English, in the last 10 years. Results of effects of vaccination on prevention
      of OME from the included RCTs were utilized to conduct a meta-analysis to find
      out the preventive value of antipneumococcal vaccination. Three RCTs were
      identified conforming to the inclusion criteria. Meta-analysis of results showed
      no significant preventive advantage for antipneumococcal vaccination. Based on
      the results it was confirmed that neither primary nor secondary prevention by
      antipneumococcal vaccination has a beneficial impact on OME. More RCTs should be
      conducted to study the effect of vaccination on OME.

PMID- 22389092
TI  - Noise-induced hearing threshold shift among US adults and implications for noise
      induced hearing loss: National Health and Nutrition Examination Surveys.
AB  - The objective of this study was to estimate the prevalence and evaluate the
      associated risk factors of the noise-induced hearing threshold shift (NITS) in
      the US adult population based on the National Health and Nutrition Examination
      Surveys (NHANES). The study population consisted of 5,418 individuals aged 20-69
      years who had complete audiologic data from the NHANES database. Stringent
      criteria were used to define NITS. Prevalence of unilateral, bilateral, and total
      NITS and their association with several socio-demographic and hearing-related
      factors were evaluated. The prevalence of unilateral, bilateral, and total NITS
      was 9.4, 3.4 and 12.8%, respectively. Prevalence of bilateral NITS was higher in
      subjects with older age, male gender, white (non-Hispanic) and Hispanic
      ethnicities, education level less than or equal to high school diploma,
      married/living with partner status, Mexico as country of birth, service in armed
      forces, smoking history, diabetes, and different kinds of noise exposure. Odds of
      NITS were only higher in older people, males, and smokers. This study provides
      comprehensive information on the prevalence of NITS in the US adult population
      and its associated risk factors. More targeted interventions may be done for
      educational, preventative, and screening purposes.

PMID- 22389093
TI  - On the role of hydrogen bonds in photoinduced electron-transfer dynamics between
      9-fluorenone and amine solvents.
AB  - Using ultrafast fluorescence upconversion and mid-infrared spectroscopy, we
      explore the role of hydrogen bonds in the photoinduced electron transfer (ET)
      between 9-fluorenone (FLU) and the solvents trimethylamine (TEA) and
      dimethylamine (DEA). FLU shows hydrogen-bond dynamics in the methanol solvent
      upon photoexcitation, and similar effects may be anticipated when using DEA,
      whereas no hydrogen bonds can occur in TEA. Photoexcitation of the electron
      acceptor dye molecule FLU with a 400 nm pump pulse induces ultrafast ET from the
      amine solvents, which is followed by 100 fs IR probe pulses as well as
      fluorescence upconversion, monitoring the time evolution of marker bands of the
      FLU S(1)  state and the FLU radical anion, and an overtone band of the amine
      solvent, marking the transient generation of the amine radical cation. A
      comparison of the experimentally determined forward charge-separation and
      backward charge-recombination rates for the FLU-TEA and FLU-DEA reaction systems
      with the driving-force dependencies calculated for the forward and backward ET
      rates reveals that additional degrees of freedom determine the ET reaction
      dynamics for the FLU-DEA system. We suggest that hydrogen bonding between the DEA
      molecules plays a key role in this behaviour.

PMID- 22389094
TI  - To name or to describe: shared knowledge affects referential form.
AB  - The notion of common ground is important for the production of referring
      expressions: In order for a referring expression to be felicitous, it has to be
      based on shared information. But determining what information is shared and what
      information is privileged may require gathering information from multiple
      sources, and constantly coordinating and updating them, which might be
      computationally too intensive to affect the earliest moments of production.
      Previous work has found that speakers produce overinformative referring
      expressions, which include privileged names, violating Grice's Maxims, and
      concluded that this is because they do not mark the distinction between shared
      and privileged information. We demonstrate that speakers are in fact quite
      effective in marking this distinction in the form of their utterances.
      Nonetheless, under certain circumstances, speakers choose to overspecify
      privileged names.

PMID- 22389095
TI  - Interfaces of ionic liquids.

PMID- 22389097
TI  - Facile oxygen reduction on a three-dimensionally ordered macroporous graphitic
      C3N4/carbon composite electrocatalyst.
AB  - Honeycomb catalysis: a facile oxygen reduction reaction has been observed on a
      graphitic C(3)N(4)/carbon catalyst with three-dimensional interconnected
      macropores (see picture with SiO(2) template). This material not only shows
      catalytic activity that is comparable to that of commercial Pt/C, but also has
      much higher organic-fuel tolerance and long-term stability.

PMID- 22389096
TI  - Identification and removal of nitroxide spin label contaminant: impact on PRE
      studies of alpha-helical membrane proteins in detergent.
AB  - NMR paramagnetic relaxation enhancement (PRE) provides long-range distance
      constraints (~15-25 A) that can be critical to determining overall protein
      topology, especially where long-range NOE information is unavailable such as in
      the case of larger proteins that require deuteration. However, several challenges
      currently limit the use of NMR PRE for alpha-helical membrane proteins. One
      challenge is the nonspecific association of the nitroxide spin label to the
      protein-detergent complex that can result in spurious PRE derived distance
      restraints. The effect of the nitroxide spin label contaminant is evaluated and
      quantified and a robust method for the removal of the contaminant is provided to
      advance the application of PRE restraints to membrane protein NMR structure
      determination.

PMID- 22389098
TI  - Utilization and evaluation of CHO-specific sequence databases for mass
      spectrometry based proteomics.
AB  - Recently released sequence information on Chinese hamster ovary (CHO) cells
      promises to not only facilitate our understanding of these industrially important
      cell factories through direct analysis of the sequence, but also to enhance
      existing methodologies and allow new tools to be developed. In this article we
      demonstrate the utilization of CHO specific sequence information to improve mass
      spectrometry (MS) based proteomic identification. The use of various CHO specific
      databases enabled the identification of 282 additional proteins, thus increasing
      the total number of identified proteins by 40-50%, depending on the sample source
      and methods used. In addition, a considerable portion of those proteins that were
      identified previously based on inter-species sequence homology were now
      identified by a larger number of peptides matched, thus increasing the confidence
      of identification. The new sequence information offers improved interpretation of
      proteomic analyses and will, in the years to come, prove vital to unraveling the
      CHO proteome.

PMID- 22389099
TI  - Thromboresistant and endothelialization effects of dopamine-mediated heparin
      coating on a stent material surface.
AB  - Heparinization of surfaces has proven a successful strategy to prevent thrombus
      formation. Inspired by the composition of adhesive proteins in mussels, the
      authors used dopamine to immobilize heparin on a stent surface. This study aimed
      to assess the thromboresistant and endothelialization effects of dopamine
      mediated heparin (HPM) coating on a stent material surface. The HPM was
      synthesized by bonding dopamine and heparin chemically. Cobalt-chromium (Co-Cr)
      alloy disks were first placed in the HPM solution and applied to surface
      stability then underwent thromboresistant tests and human umbilical vein
      endothelial cells (HUVEC) cytotoxicity assays. The results showed not only
      thromboresistant activity and a stable state of heparin on the surfaces after
      investigation with toluidine blue and thrombin activation assay but also
      proliferation of HUVEC in vitro. Studies on animals showed that the HPM-coated
      stent has no obvious inflammation response and increasing of restenosis rate
      compared to the bare metal stent (BMS) indicating good biocompatibility as well
      as safety in its in vivo application. Moreover, improving the endothelial cell
      (EC) proliferation resulted in a higher strut-covering rate (i.e.,
      endothelialization) with shuttle-shaped EC in the HPM-coated stent group compared
      to that of the BMS group. These results suggest that this facile coating approach
      could significantly promote endothelialization and offer greater safety than the
      BMS for its much improved thromboresistant property. Moreover, it may offer a
      platform for conjugating secondary drugs such as anti-proliferative drugs.

PMID- 22389100
TI  - Effect of hydrazine based deproteination protocol on bone mineral crystal
      structure.
AB  - In several bone deproteination protocols the chemical agent used for protein
      cleavage is hydrazine. The effect of hydrazine deproteination method on the
      crystal size and crystallinity of the bone mineral was studied. Bovine bones were
      subjected to this protocol and the crystal size and crystallinity of the
      remaining bone mineral were determined by X-ray Diffraction (XRD), by measuring
      the width at the half of the maximum intensity of the (002) reflection. It was
      found that hydrazine deproteination induces noteworthy increase of crystal size
      and crystallinity. The effect was enhanced by increasing hydrazine temperature
      from 25 to 55 degrees C. Furthermore, infrared spectroscopy revealed that
      hydrazine facilitates the removal of carbonate and acid phosphate ions from bone
      mineral. It is proposed that the mechanism of modification of crystal size and
      crystallinity lies on the removal of these ions thus, resulting in crystal re
      organization.

PMID- 22389102
TI  - Mentorship in scientific writing.

PMID- 22389101
TI  - Substituted hydroxyapatites for bone repair.
AB  - Calcium phosphates such as hydroxyapatite have a wide range of applications both
      in bone grafts and for the coating of metallic implants, largely as a result of
      their chemical similarity to the mineral component of bone. However, to more
      accurately mirror the chemistry, various substitutions, both cationic
      (substituting for the calcium) and anionic (substituting for the phosphate or
      hydroxyl groups) have been produced. Significant research has been carried out in
      the field of substituted apatites and this paper aims to summarise some of the
      key effect of substitutions including magnesium, zinc, strontium, silicon and
      carbonate on physical and biological characteristics. Even small substitutions
      have been shown to have very significant effects on thermal stability,
      solubility, osteoclastic and osteoblastic response in vitro and degradation and
      bone regeneration in vivo.

PMID- 22389104
TI  - How do thermophilic proteins resist aggregation?
AB  - Aggregation is an ancient threat that must be overcome by proteins from all
      organisms to maintain their native functional states. This is essential for the
      maintenance of metabolic flux and viability of their cellular machineries. Here,
      we compare the aggregation-resistance strategies adapted by the thermophilic
      proteins and their mesophilic homologs using a dataset of 373 protein families.
      Like their mesophilic homologs, the thermophilic protein sequences also contain
      potential aggregation prone regions (APRs), capable of forming cross-beta motif
      and amyloid-like fibrils. Tetrapeptide and hexapeptide amyloid-like fibril
      forming sequence patterns and experimentally proven amyloid-like fibril forming
      peptide sequences were also detected in the thermophilic proteins. Both the
      thermophilic and the mesophilic proteins use similar strategies to resist
      aggregation. However, the thermophilic proteins show superior utilization of
      these strategies. The thermophilic protein monomers show greater ability to "stow
      away" the APRs in the hydrophobic cores to protect them from solvent exposure.
      The thermophilic proteins are also better at gatekeeping the APRs by surrounding
      them with charged residues (Asp, Glu, Lys, and Arg) and Pro to a greater extent.
      While thermophilic and mesophilic proteins in our dataset are highly homologous
      and show strong overall sequence conservation, the APRs are not conserved between
      the homologs. These findings indicate that evolution is working to avoid
      amyloidogenic regions in proteins. Our results are also consistent with the
      observation that thermophilic cells often accumulate small molecule osmolytes
      capable of stabilizing their proteins and other macromolecules. This study has
      important implications for rational design and formulation of therapeutic
      proteins and antibodies.

PMID- 22389103
TI  - Physical activity is related to insulin sensitivity in children and adolescents,
      independent of adiposity: a review of the literature.
AB  - In adults, there is evidence that physical activity effectively improves insulin
      sensitivity regardless of adiposity. Whether this is also the case in children
      and adolescents is less clear. Clarifying this matter may help to identify the
      best outcomes to target in exercise programs for these age groups, where changes
      in adiposity may not always be desirable or realistic. A review of the literature
      was conducted on studies that examined the relationships of physical activity,
      cardiorespiratory fitness and strength with insulin sensitivity independent of
      adiposity in children and adolescents. Experimental (intervention) and
      correlational (longitudinal and cross-sectional) studies on participants ages 18
      years and younger were identified. A total of 42 studies were included in this
      review. Sample sizes in the studies ranged from 14 to 4955 participants, with
      individual ages ranging from 5 to 19 years. A significant relationship with
      insulin sensitivity existed in 78% of studies on physical activity, 69% of
      studies on cardiorespiratory fitness and 66% of studies on strength. In studies
      that examined both physical activity and cardiorespiratory fitness concurrently,
      evidence suggests that they are both correlated with insulin sensitivity
      independent of adiposity, especially when physical activity is at higher
      intensities. However, the strength of this relationship might be influenced by
      study design, measurement techniques and participant characteristics. This is the
      first review of its type to take research design into account and to examine
      study outcomes according to participant ethnicity, gender, age, pubertal status
      and weight status.

PMID- 22389105
TI  - Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure.
AB  - In AL amyloidosis prognosis depends on the severity of heart dysfunction which is
      best assessed by natriuretic peptides (BNP and NT-proBNP). However, their
      clearance relies on glomerular filtration rate (GFR) and their concentration
      increases with renal failure. We evaluated the diagnostic and prognostic
      performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with
      different degrees of renal failure. Patients were grouped according to GFR. Group
      1 comprised 109 patients with GFR >=60 mL/min/1.73 m(2) , Group 2, 77 subjects
      with GFR <60 and >=15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15
      mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heart
      involvement and to predict survival in the three groups was assessed. Decreasing
      eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart
      involvement and predicting survival. Both natriuretic peptides were independent
      prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently
      predicted survival. Natriuretic peptides are powerful and useful markers of
      cardiac dysfunction and prognosis, provided that eGFR is considered in
      interpreting their clinical meaning. BNP should be preferred in patients with end
      stage renal failure.

PMID- 22389106
TI  - Copper-catalyzed highly regio- and stereoselective directed hydroboration of
      unsymmetrical internal alkynes: controlling regioselectivity by choice of
      catalytic species.

PMID- 22389107
TI  - Facial dysmorphopsia: a notable variant of the "thin man" phenomenon?
AB  - BACKGROUND: The aim of this work is to investigate the facial distortion
      (dysmorphopsia) experienced by patients with homonymous paracentral scotomas and
      to analyze the interrelationship with the previously described "thin man"
      phenomenon. METHODS: Routine neuro-ophthalmological examination and brain MRI in
      three patients who suffered from small homonymous paracentral scotomas due to
      infarction or arteriovenous malformations of the occipital lobe. They all
      complained of distortion and shrinkage of their interlocutor's face contralateral
      to the brain lesion. The phenomenon appeared some seconds after steady fixation
      on the interlocutor's nose and was evident with both left and right homonymous
      scotomas. The patients did not notice a gap in the area corresponding to the
      scotoma and objects other than faces were perceived normally. RESULTS: Homonymous
      paracentral scotomas can lead to focal displacement of facial features towards
      the center of the field defect with resulting distortion of the face on the
      affected side. This so-called "dysmorphopsia" makes faces appear regionally
      narrower than they are in reality and may be induced even by visual field defects
      that remain undetected by conventional perimetry using 6 degrees  * 6 degrees 
      grids. Predilection for faces is probably associated with the superior location
      of scotomas or specific impairment of face processing abilities related to the
      lesion site. CONCLUSIONS: Facial dysmorphopsia is most probably associated with
      cortical "filling-in" and spatial distortion, and can hence be regarded as a
      special entity of the "thin man" phenomenon.

PMID- 22389109
TI  - The interplay between gesture and speech in the production of referring
      expressions: investigating the tradeoff hypothesis.
AB  - The tradeoff hypothesis in the speech-gesture relationship claims that (a) when
      gesturing gets harder, speakers will rely relatively more on speech, and (b) when
      speaking gets harder, speakers will rely relatively more on gestures. We tested
      the second part of this hypothesis in an experimental collaborative referring
      paradigm where pairs of participants (directors and matchers) identified targets
      to each other from an array visible to both of them. We manipulated two factors
      known to affect the difficulty of speaking to assess their effects on the gesture
      rate per 100 words. The first factor, codability, is the ease with which targets
      can be described. The second factor, repetition, is whether the targets are old
      or new (having been already described once or twice). We also manipulated a third
      factor, mutual visibility, because it is known to affect the rate and type of
      gesture produced. None of the manipulations systematically affected the gesture
      rate. Our data are thus mostly inconsistent with the tradeoff hypothesis.
      However, the gesture rate was sensitive to concurrent features of referring
      expressions, suggesting that gesture parallels aspects of speech. We argue that
      the redundancy between speech and gesture is communicatively motivated.

PMID- 22389108
TI  - Protein determinants of phage T4 lysis inhibition.
AB  - Genetic studies have established that lysis inhibition in bacteriophage T4
      infections occurs when the RI antiholin inhibits the lethal hole-forming function
      of the T holin. The T-holin is composed of a single N-terminal transmembrane
      domain and a ~20 kDa periplasmic domain. It accumulates harmlessly throughout the
      bacteriophage infection cycle until suddenly causing permeabilization of the
      inner membrane, thereby initiating lysis. The RI antiholin has a SAR domain that
      directs its secretion to the periplasm, where it can either be inactivated and
      degraded or be activated as a specific inhibitor of T. Previously, it was shown
      that the interaction of the soluble domains of these two proteins within the
      periplasm was necessary for lysis inhibition. We have purified and characterized
      the periplasmic domains of both T and RI. Both proteins were purified in a
      modified host that allows disulfide bond formation in the cytoplasm, due to the
      functional requirement of conserved disulfide bonds. Analytical centrifugation
      and circular dichroism spectroscopy showed that RI was monomeric and exhibited
      ~80% alpha-helical content. In contrast, T exhibited a propensity to oligomerize
      and precipitate at high concentrations. Incubation of RI with T inhibits this
      aggregation and results in a complex of equimolar T and RI content. Although gel
      filtration analysis indicated a complex mass of 45 kDa, intermediate between the
      predicted 30 kDa heterodimer and 60 kDa heterotetramer, sedimentation velocity
      analysis indicated that the predominant species is the former. These results
      suggest that RI binding to T is necessary and sufficient for lysis inhibition.

PMID- 22389110
TI  - GC-MS and GC-IRD studies on brominated dimethoxyamphetamines: regioisomers
      related to 4-Br-2,5-DMA (DOB).
AB  - A series of regioisomeric bromodimethoxyamphetamines have mass spectra
      essentially equivalent to the controlled drug substance 4-Br-2,5
      dimethoxyamphetamine (4-Br-2,5-DMA; DOB); all have molecular weight of 274 and
      major fragment ions in their electron ionization mass spectra at m/z 44 and m/z
      230/232. The trifluoroacetyl, pentafluoropropionyl and heptafluorobutryl
      derivatives of the primary regioisomeric amines were prepared and evaluated in
      gas chromatography-mass spectrometry (GC-MS) studies. The mass spectra for these
      derivatives did not show unique fragment ions for specific identification of
      individual isomers. However, the mass spectra do serve to divide the compounds
      into three groups, depending on their base peak. Gas chromatography with infrared
      detection (GC-IRD) provides direct confirmatory data for the identification of
      the designer drug 4-bromo-2,5-dimethoxyamphetamine from the other regioisomers
      involved in the study. The perfluoroacylated derivatives of the six regioisomeric
      bromodimethoxyamphetamines were successfully resolved on non-polar stationary
      phases such as a 100% dimethylpolysiloxane stationary phase (Rtx-1) and 50%
      phenyl - 50% methyl polysiloxane (Rxi-50).

PMID- 22389111
TI  - Endocytosis at the nanoscale.
AB  - Endocytosis is a fundamental process in which eukaryotic cells internalise
      molecules and macromolecules via deformation of the membrane and generation of
      membrane-bound carriers. Functional aspects are not only limited to uptake of
      nutrients, but also play a primary role in evolutionary conserved processes such
      as the regulation of plasma membrane protein activity (i.e. signal-transducing
      receptors, small-molecule transporters and ion channels), cell motility and
      mitosis. The macromolecular nature of the material transported by endocytosis
      makes this route one of the most important targets for nanomedicine. Indeed, many
      nanoparticle formulations have been customised to enter cells through endocytosis
      and deliver the cargo within the cell. In this critical review, we present an
      overview of the biology of endocytosis and discuss its implications in cell
      internalisation of nanoparticles. We discuss how nanoparticle size, shape and
      surface chemistry can control this process effectively. Finally, we discuss
      different drug delivery strategies on how to evade lysosomal degradation to
      promote effective release of the cargo (376 references).

PMID- 22389112
TI  - The ubiquitin-proteasome pathway regulates claudin 5 degradation.
AB  - The tight junctions (TJs) form continuous intracellular contacts, which help
      create selective barriers in epithelial and endothelial cell layers. The
      structures created by the TJs are very dynamic and can be rapidly remodeled in
      response to physiological and pathological signals. Claudin 5 is a membranal TJ
      protein which plays a critical role in determining the permeability of
      endothelial barriers. We describe the regulation of claudin 5 degradation by the
      ubiquitin-proteasome system (UPS). Our results indicate that claudin 5 has a
      relatively short half-life and can be polyubiquitinated on lysine 199. This
      ubiquitination appears to trigger the proteasome-dependent degradation of claudin
      5. Other mechanisms also seem to be involved in the post-translational regulation
      of claudin 5, including a ubiquitin-independent and probably indirect lysosomal
      dependent pathway. These findings provide evidence for the involvement of the UPS
      in the regulation of claudin 5 levels, and set the stage for further research to
      determine the involvement of this pathway in the modulation of the properties of
      TJs and cell-layer barriers.

PMID- 22389114
TI  - Atropoisomeric (P,N) ligands for the highly enantioselective Pd-catalyzed
      intramolecular asymmetric alpha-arylation of alpha-branched aldehydes.
AB  - Three-in-one: a short synthetic route readily gives access to a new class of
      chiral (P,N) ligands characterized by three distinct elements of chirality. These
      ligands are highly enantioselective in the challenging Pd-catalyzed
      intramolecular asymmetric alpha-arylation of alpha-branched aldehydes.

PMID- 22389113
TI  - Meta-analysis of individual patient data to examine factors affecting growth and
      rupture of small abdominal aortic aneurysms.
AB  - BACKGROUND: Surveillance is a common management strategy for small abdominal
      aortic aneurysm (AAA) (3.0-5.4 cm in diameter). Individual characteristics, other
      than diameter, may influence aneurysm growth or rupture rates. METHODS:
      Individual data were collated from 15 475 people under follow-up for a small
      aneurysm in 18 studies. The influence of co-variables (including demographics,
      medical and drug history) on aneurysm growth and rupture rates (analysed using
      longitudinal random-effects modelling and survival analysis with adjustment for
      aneurysm diameter) were summarized in an individual patient meta-analysis.
      RESULTS: The mean aneurysm growth rate of 2.21 mm/year was independent of age and
      sex. Growth rate was increased in smokers (by 0.35 mm/year) and decreased in
      patients with diabetes (by 0.51 mm/year). Mean arterial pressure had no effect
      and antihypertensive or other cardioprotective medications had only small, non
      significant effects on aneurysm growth, consistent with the observation that
      calendar year of enrollment was not associated with growth rate. Rupture rates
      were almost fourfold higher in women than men (P < 0.001), were double in current
      smokers (P = 0.001) and increased with higher blood pressure (P = 0.001).
      CONCLUSION: Follow-up schedules for individuals with a small AAA may need to
      consider diabetes and smoking, in addition to aneurysm diameter. The differing
      risk factors for growth and rupture suggest that a lower threshold for surgical
      intervention in women may be justified. No single drug used for cardiovascular
      risk reduction had a major effect on the growth or rupture of small aneurysms.

PMID- 22389115
TI  - Segmental isotope labeling of proteins for NMR structural study using a protein S
      tag for higher expression and solubility.
AB  - A common obstacle to NMR studies of proteins is sample preparation. In many
      cases, proteins targeted for NMR studies are poorly expressed and/or expressed in
      insoluble forms. Here, we describe a novel approach to overcome these problems.
      In the protein S tag-intein (PSTI) technology, two tandem 92-residue N-terminal
      domains of protein S (PrS(2)) from Myxococcus xanthus is fused at the N-terminal
      end of a protein to enhance its expression and solubility. Using intein
      technology, the isotope-labeled PrS(2)-tag is replaced with non-isotope labeled
      PrS(2)-tag, silencing the NMR signals from PrS(2)-tag in isotope-filtered (1)H
      detected NMR experiments. This method was applied to the E. coli ribosome binding
      factor A (RbfA), which aggregates and precipitates in the absence of a
      solubilization tag unless the C-terminal 25-residue segment is deleted
      (RbfADelta25). Using the PrS(2)-tag, full-length well-behaved RbfA samples could
      be successfully prepared for NMR studies. PrS(2) (non-labeled)-tagged RbfA
      (isotope-labeled) was produced with the use of the intein approach. The well
      resolved TROSY-HSQC spectrum of full-length PrS(2)-tagged RbfA superimposes with
      the TROSY-HSQC spectrum of RbfADelta25, indicating that PrS(2)-tag does not
      affect the structure of the protein to which it is fused. Using a smaller PrS
      tag, consisting of a single N-terminal domain of protein S, triple resonance
      experiments were performed, and most of the backbone (1)H, (15)N and (13)C
      resonance assignments for full-length E. coli RbfA were determined. Analysis of
      these chemical shift data with the Chemical Shift Index and heteronuclear (1)H
      (15)N NOE measurements reveal the dynamic nature of the C-terminal segment of the
      full-length RbfA protein, which could not be inferred using the truncated
      RbfADelta25 construct. CS-Rosetta calculations also demonstrate that the core
      structure of full-length RbfA is similar to that of the RbfADelta25 construct.

PMID- 22389116
TI  - Cardiovascular disease: the female heart is vulnerable: a call to action from the
      10Q report.
AB  - February was Heart Month. Clinical Cardiology has embraced the opportunity to
      share with clinicians and scientists the major adverse impact of cardiovascular
      disease in women, identifying actionable items derived from recent research
      studies and highlighting gaps in our knowledge that require investigation.

PMID- 22389118
TI  - Noninvasive diagnostic techniques for coronary disease in women.
AB  - Significant advances in medical treatment, medical technology, and the focus on
      sex-specific research have contributed to a reduction in cardiovascular mortality
      in women. Despite these advances, coronary artery disease (CAD) is the leading
      cause of cardiovascular death of women in the Western world. In the past 2
      decades, the focused research on women at risk for CAD has helped to clarify our
      understanding of some of the sex-specific factors that are important in the
      detection of CAD. In women, the detection and evaluation of physiologically
      significant CAD can be challenging. Many of the traditional tests that are
      designed to detect focal areas of coronary artery stenosis are less sensitive and
      specific in female patients, who have a greater burden of symptoms, higher
      atherosclerotic burden, and lower prevalence of obstructive coronary disease. In
      this article, we review the available evidence on the role of contemporary
      noninvasive diagnostic techniques in the evaluation of women with symptoms of
      CAD. The authors have no funding, financial relationships, or conflicts of
      interest to disclose.

PMID- 22389119
TI  - Coronary revascularization in women.
AB  - Historically, mortality rates have been higher in women than in men for both PCI
      and CABG. Recent registries and studies have shown that women have mortality
      rates similar to men after correcting for age and comorbidities. The gender gap
      is narrowing with respect to outcomes for women with both PCI and CABG.
      Revascularization with PCI and CABG in women with stable angina (SA), unstable
      angina (UA), non ST-elevation myocardial infarction (NSTEMI), and ST-elevation
      myocardial infarction (STEMI) will all be reviewed in light of the most recent
      studies and registries.

PMID- 22389117
TI  - Myocardial ischemia in women: lessons from the NHLBI WISE study.
AB  - Cardiovascular disease (CVD) remains the leading cause of death for women. For
      almost 3 decades, more women than men have died from CVD, with the most recent
      annual statistics on mortality reporting that CVD accounted for 421 918 deaths
      among women in the United States. Although there have been significant declines
      in coronary heart disease (CHD) mortality for females, these reductions lag
      behind those seen in men. In addition, where there has been a decrease in
      mortality from CHD across all age groups over time in men, in the youngest women
      (age <55 years) there has been a notable increase in mortality from CHD. There
      are differences in the prevalence, symptoms, and pathophysiology of myocardial
      ischemia that occurs in women compared with men. In this paper, we review the
      pathophysiology and mechanisms of ischemic heart disease (IHD) in women,
      particularly focusing on what we have learned from the WISE study. We examine the
      sex-specific issues related to myocardial ischemia in women in terms of
      prevalence and prognosis, traditional and novel risk factors, diagnostic testing,
      as well as therapeutic management strategies for IHD.

PMID- 22389120
TI  - Preeclampsia and hypertensive disease in pregnancy: their contributions to
      cardiovascular risk.
AB  - More women than men die each year of cardiovascular disease, which remains the
      leading cause of death in the United States. Sex-specific factors, including
      pregnancy-related disorders, should be considered when assessing cardiovascular
      (CV) risk in women. Hypertensive disorders of pregnancy have been associated with
      CV risk later in life and may identify women in whom earlier primary prevention
      may reduce their risk. This article reviews the physiologic changes in blood
      pressure during pregnancy, current definitions of hypertensive diseases of
      pregnancy and preeclampsia, and postulated pathophysiologic mechanisms leading to
      preeclampsia that might contribute to later CV risk. Also summarized are studies
      providing evidence on the association between hypertensive diseases of pregnancy
      and future CV risk.

PMID- 22389121
TI  - Arrhythmias in women.
AB  - There are important gender differences in cardiac electrophysiology that affect
      the epidemiology, presentation, and prognosis of various arrhythmias. Women have
      been noted to have higher resting heart rates compared to men. They also have a
      longer QT interval, which puts them at an increased risk for drug-induced
      torsades de pointes. Women with atrial fibrillation are at a higher risk of
      stroke, and they are less likely to receive anticoagulation and ablation
      procedures compared to men. Women have a lower risk of sudden cardiac death and
      are less likely to have known coronary artery disease at the time of an event
      compared to men. Both men and women have been shown to derive an equal survival
      benefit from implantable cardioverter defibrillators and cardiac
      resynchronization therapy, although these devices are significantly underutilized
      in women. Women also appear to have a better response to cardiac
      resynchronization therapy in terms of reduced numbers of hospitalizations and
      more robust reverse ventricular remodeling. Further studies are required to
      elucidate the underlying pathophysiology of these sex differences in cardiac
      arrhythmias.

PMID- 22389122
TI  - Heart failure in women.
AB  - Heart failure (HF) has steadily increased in prevalence and affects both males
      and females equally. Despite this, there has been a significant
      underrepresentation of women in large scale HF trials. This disparity has lead to
      a deficit in understanding important gender-based differences in pathophysiology,
      diagnosis and treatment strategies. We review these gaps and explore a biological
      basis for varying outcomes. Endogenous estrogen plays an important role in
      epidemiology and outcome. The administration of exogenous estrogen has had varied
      success in treatment and is outlined extensively below. Additionally, we
      highlight unique HF syndromes through pregnancy and important sex-specific issues
      concerning transplant and mechanical circulatory support. A central theme
      remains: there is a clear need for increased female recruitment in clinical
      trials, and more studies exploring the role of gender-based biology in HF
      treatment.

PMID- 22389123
TI  - Spinal hernia tissue autofluorescence spectrum.
AB  - The laser intervertebral disc decompression may provide appropriate relief in
      properly selected patients with contained disc herniations. The present
      investigation aims to characterise intervertebral disc material by
      autofluorescence induced by laser light. Degeneration of the intervertebral disc
      is associated with progressive biochemical changes in disc material. Percutaneous
      laser disc decompression has become rather popular for the treatment of lumbar
      disc herniation, but there are problems in the selection of patients. For this
      purpose, recognition of the disc composition is necessary. We propose a new type
      of spectroscopic investigation. It is advantageous to the characterization of
      intervertebral disc material. Intervertebral disc specimens were removed during
      open surgery from different disc locations. Preoperative patients' MRI was
      evaluated using the Pfirrmann disc degeneration and Komori scale for migrating of
      herniated nucleus pulposus. Adjacent slices of stained disc sections were
      evaluated by histology/histochemistry and autofluorescence spectra. Comparison of
      the MRI, spectral, histological and histochemical data was performed. The MRI
      Komori scale correlated with the histology Boos degeneration index. In the
      histochemistry, collagens other than collagens I and II of the disc were
      distinguished with best positive correlation coefficient (0.829) and best
      negative one (-0.904) of proteoglycans of sequester to Boos index. A correlation
      of the IV Gaussian component of the hernia spectra with the Boos index was
      established. The Gaussian component correlation with different collagen types and
      proteoglycan was determined for the disc and sequester. "Autofluorescence-based
      diagnosis" refers to the evaluation of disc degeneration by histological and
      histochemical evaluation; it can provide additional data on the degeneration of
      an intervertebral disc.

PMID- 22389124
TI  - Induction of beta-cell resistance to hypoxia and technologies for oxygen delivery
      to transplanted pancreatic islets.
AB  - Hypoxia is believed to be a crucial factor involved in cell adaptation to
      environmental stress. Islet transplantation, especially with immunoisolated
      islets, interrupts vascular connections, resulting in the substantially decreased
      delivery of oxygen and nutrients to islet cells. Insulin-producing pancreatic
      beta cells are known to be highly susceptible to oxygen deficiency. Such
      susceptibility to hypoxia is believed to be one of the main causes of beta-cell
      death in the post-transplantation period. Different strategies have been
      developed for the protection of beta cells against hypoxic injury and for oxygen
      delivery to transplanted islets. The enhancement of beta-cell defense properties
      against hypoxia has been achieved using various techniques such as gene
      transfection, drug supplementation, co-culturing with stem cells and cell
      selection. Technologies for oxygen delivery to transplanted islets include local
      neovascularization of subcutaneous sites, electrochemical and photosynthetic
      oxygen generation, oxygen refuelling of bio-artificial pancreas and whole body
      oxygenation by using hyperbaric therapy. Progress in the field of oxygen
      technologies for islet transplantation requires a multidisciplinary approach to
      explore and optimize the interaction between components of the biological system
      and different technological processes. This review article focuses mainly on the
      recently developed strategies for oxygenation and protection from hypoxic injury 
      to achieve stable and long-term normoglycaemia in diabetic patients with
      transplanted pancreatic islets.

PMID- 22389125
TI  - Anti-malarials exert a protective effect while Mestizo patients are at increased
      risk of developing SLE renal disease: data from a Latin-American cohort.
AB  - OBJECTIVE: To examine the role of ethnicity and the use of anti-malarials
      (protective) on lupus renal disease. METHODS: A nested case-control study (1:2
      proportion, n = 265 and 530) within GLADEL's (Grupo Latino Americano De Estudio
      de Lupus) longitudinal inception cohort was carried out. The end-point was ACR
      renal criterion development after diagnosis. Cases and controls were matched for
      follow-up time (end-point or a comparable time, respectively). Renal disease
      predictors were examined by univariable and multivariable analyses. Additional
      analyses were done to determine if the protective effect of anti-malarials
      persisted after adjusting for intake-associated confounders. RESULTS: Of the
      cases, 233 (87.9%) were women; their mean (s.d.) age at diagnosis was 28.0 (11.9)
      years and their median (Q3-Q1 interquartile range) follow-up time for cases and
      controls was 8.3 months (Q3-Q1: 23.5); 56.6% of the cases and 74.3% of the
      controls were anti-malarial users. Mestizo ethnicity [odds ratio (OR) 1.72, 95%
      CI 1.19, 2.48] and hypertension (OR 2.26, 95% CI 1.38, 3.70) were independently
      associated with a higher risk of renal disease, whereas anti-malarial use (OR
      0.39, 95% CI 0.26, 0.58), older age at disease onset (OR 0.98, 95% CI 0.96, 0.99)
      and female gender (OR 0.56, 95% CI 0.32, 0.99) were negatively associated with
      such occurrence. After adjusting for variables associated with their intake, the
      protective effect of anti-malarials on renal disease occurrence persisted (OR
      0.38, 95% CI 0.25, 0.58). CONCLUSION: Mestizo patients are at increased risk of
      developing renal disease, whereas anti-malarial use protects patients from such
      an occurrence.

PMID- 22389126
TI  - B-cell chronic lymphocytic leukaemia presenting as lower motor neuron disease and
      SS.

PMID- 22389127
TI  - Functional status in severe juvenile idiopathic arthritis in the biologic
      treatment era: an assessment in a French paediatric rheumatology referral centre.
AB  - OBJECTIVES: To investigate the functional status of difficult-to-treat JIA
      patients, including patients receiving biotherapies, and to correlate functional
      status to disease activity. METHODS: All JIA patients consecutively evaluated in
      a paediatric rheumatology referral centre (November 2008 to March 2009) were
      enrolled in an observational cross-sectional study. The Childhood HAQ (CHAQ),
      physician's assessment of overall disease activity, parent's assessment of well
      being and pain, and active and limited joint numbers were measured. RESULTS: We
      enrolled 95 patients [27% systemic, 29% polyarticular, 22% enthesitis-related
      arthritis (ERA) and 23% oligoarticular JIA]. Median disease duration was 3.5
      years. Treatment included NSAIDs (56%), MTX (23%), CSs (21%) and biologics (45%).
      Of all patients, 31 and 56%, respectively, had inactive and minimally active
      disease. The median CHAQ score was 0.375 (range 0-3). Most patients had no or
      mild functional disability (61%), impaired well-being (63%) or pain (55%); 10%
      reported severely impaired function and well-being, 19% severe pain. ERA patients
      reported worse well-being and pain. CHAQ scores correlated with disease activity.
      Long-lasting disease and biologic treatment were associated with better well
      being and pain scores. CONCLUSION: Despite the high proportion of severe JIA
      patients in this cohort, CHAQ values are within the lower range of recent
      reports, probably related to new therapeutic approaches. Impaired function and
      well-being remain a challenge for at least 10% of the patients. Impaired well
      being and pain in ERA patients require further study. The strong correlation
      between functional status and well-being underlines the importance of improving
      function to optimize quality of life.

PMID- 22389128
TI  - Analgesic and uterine relaxant effects of isoliquiritigenin, a flavone from
      Glycyrrhiza glabra.
AB  - Shaoyao-gancao-tang, a Chinese medicinal formula consisting of peony and licorice
      has been used for the treatment of dysmenorrhea for thousands of years. The
      purpose of the present study was to demonstrate the analgesic and uterine
      relaxant effects of isoliquiritigenin (ISL), a flavonoid isolated from the roots
      of Glycyrrhiza glabra (a type of licorice). In vitro, isoliquiritigenin caused
      concentration-dependent inhibition of spontaneous contraction of isolated rat
      uterus and the contraction induced by various types of stimulants, such as
      acetylcholine (Ach, 10 mM), KCl (40 mM) and oxytocin (1 mU/mL). The uterine
      contractile response to cumulative concentrations of CaCl2 was blocked by 0.1 and
      1 mM of isoliquiritigenin. The isoliquiritigenin-induced relaxation was partly
      inhibited by the nitric oxide synthase (NOS) inhibitor Nv-nitro-L-arginine
      methylester (L-NAME, 100 mM) and the COX-1/COX-2 inhibitor indomethacin (10mM).
      In vivo, isoliquiritigenin could cause a significant reduction in the acetic acid
      induced writhing response and hot-plate test at the high dose. These results
      indicate that isoliquiritigenin, a flavonoid isolated from the roots of
      Glycyrrhiza glabra, not only has a spasmolytic effect on uterine contraction,
      which is in relation to Ca2+ channels, NOS and COX, but also an effective
      activity in reducing pain.

PMID- 22389129
TI  - Underspecification of cognitive status in reference production: some empirical
      predictions.
AB  - Within the Givenness Hierarchy framework of Gundel, Hedberg, and Zacharski
      (1993), lexical items included in referring forms are assumed to conventionally
      encode two kinds of information: conceptual information about the speaker's
      intended referent and procedural information about the assumed cognitive status
      of that referent in the mind of the addressee, the latter encoded by various
      determiners and pronouns. This article focuses on effects of underspecification
      of cognitive status, establishing that, although salience and accessibility play
      an important role in reference processing, the Givenness Hierarchy itself is not
      a hierarchy of degrees of salience/accessibility, contrary to what has often been
      assumed. We thus show that the framework is able to account for a number of
      experimental results in the literature without making additional assumptions
      about form-specific constraints associated with different referring forms.

PMID- 22389130
TI  - Novel sonomicrometry of ex vivo diaphragm after phrenic nerve injury: Role of
      matrix metalloproteinases.
AB  - Extracellular matrix (ECM) proteins and their proteolytic enzymes, matrix
      metalloproteinases (MMPs), implicate in neuromuscular junctions (NMJs) function
      during development. However, their pathophysiological mechanisms in the diaphragm
      remain obscure, because a well-characterized ex vivo experimental system has
      still been lacking. In the study, we aim to develop a novel ex vivo method of
      sonomicrometry and evaluate validity of the method with a mouse diaphragm twitch
      after phrenic nerve injury. In an ex vivo experiment using phrenic nerve-injured
      mice, diaphragm twitch during electrical pulse stimulation of phrenic nerve was
      transiently suppressed on day 1. Recombinant MMPs administered in recording
      solution exerted dose-responsive suppression on the diaphragm twitch in normal
      mice tissue. Furthermore, gelatinolytic and immunoblot experiments were performed
      to evaluate MMPs' involvement and NMJs' insults. After nerve injury, (1) in vivo
      levels of MMPs were transiently upregulated at day 1 and (2) expressions of ECM
      proteins, agrin (nicotinic acetylcholine receptor stabilizer) and laminin, were
      transiently reduced at day 1 in the diaphragm. These alterations were cancelled
      by preinjection of the MMP inhibitor. In conclusion, MMPs hamper NMJ synaptic
      function in association with the impairment of ECM milieu. Our novel experimental
      method using ex vivo sonomicrometry is necessary for examining the molecular
      pathophysiolgy for the dysfunction of NMJs in the diaphragm.

PMID- 22389131
TI  - Activity, stability, and structure of metagenome-derived LC11-RNase H1, a homolog
      of Sulfolobus tokodaii RNase H1.
AB  - Metagenome-derived LC11-RNase H1 is a homolog of Sulfolobus tokodaii RNase H1
      (Sto-RNase H1). It lacks a C-terminal tail, which is responsible for
      hyperstabilization of Sto-RNase H1. Sto-RNase H1 is characterized by its ability
      to cleave not only an RNA/DNA hybrid but also a double-stranded RNA (dsRNA). To
      examine whether LC11-RNase H1 also exhibits both RNase H and dsRNase activities,
      LC11-RNase H1 was overproduced in Escherichia coli, purified, and characterized.
      LC11-RNase H1 exhibited RNase H activity with similar metal ion preference,
      optimum pH, and cleavage mode of substrate with those of Sto-RNase H1. However,
      LC11-RNase H1 did not exhibit dsRNase activity at any condition examined. LC11
      RNase H1 was less stable than Sto-RNases H1 and its derivative lacking the C
      terminal tail (Sto-RNase H1DeltaC6) by 37 and 13  degrees C in T(m) ,
      respectively. To understand the structural bases for these differences, the
      crystal structure of LC11-RNase H1 was determined at 1.4 A resolution. The LC11
      RNase H1 structure is highly similar to the Sto-RNase H1 structure. However, LC11
      RNase H1 has two grooves on protein surface, one containing the active site and
      the other containing DNA-phosphate binding pocket, while Sto-RNase H1 has one
      groove containing the active site. In addition, LC11-RNase H1 contains more
      cavities and buried charged residues than Sto-RNase H1. We propose that LC11
      RNase H1 does not exhibit dsRNase activity because dsRNA cannot fit to the two
      grooves on protein surface and that LC11-RNase H1 is less stable than Sto-RNase
      H1DeltaC6 because of the increase in cavity volume and number of buried charged
      residues.

PMID- 22389133
TI  - Maximizing field-effect mobility and solid-state luminescence in organic
      semiconductors.
AB  - Conductive and emissive: organic transistors made from a simple styrylanthracene
      derivative have high charge mobility and high luminescence quantum yields. These
      properties are attributed to the lack of singlet fission, and challenge the idea
      that the efficient pi interactions required for high mobility always lead to
      quenching of emission. The transistors emit blue electroluminescence and are
      stable during operation and storage.

PMID- 22389132
TI  - von Willebrand disease: clinical and laboratory lessons learned from the large
      von Willebrand disease studies.
AB  - During the past 25 years, our knowledge concerning the pathogenesis, diagnostic
      strategies, and treatment of von Willebrand disease (VWD) has increased
      significantly. Following the immunological differentiation of factor VIII (FVIII)
      and von Willebrand factor (VWF) in the 1970s and the cloning of the FVIII and VWF
      genes in the mid-1980s, substantial progress has been made in our understanding
      of this, the most common inherited bleeding disorder. We now recognize that VWD
      represents a range of genetic diseases all with the clinical endpoint of
      increased mucocutaneous bleeding. The molecular pathology of Type 2 and 3 VWD is
      now comprehensively documented and involves rare sequence variants at the VWF
      locus. In contrast, the genetic causation of Type 1 disease remains incompletely
      defined and in many cases appears to involve genetic determinants in addition to
      or instead of VWF. The diagnostic triad of a personal history of excessive
      mucocutaneous bleeding, laboratory tests for VWF that are consistent with VWD,
      and a family history of the condition remain the keystone to VWD identification.
      In the laboratory, measurement of VWF antigen and function continue to be the
      most important diagnostic studies, and while our understanding of the molecular
      genetic pathology of VWD has advanced considerably in the past decade, genetic
      testing as a component of diagnosis is limited to certain distinct subtypes of
      the disorder. Treatment of VWD has been relatively unchanged for the past decade
      and continues to involve either stimulation of the release of intrinsic VWF with
      desmopressin or the infusion of VWF concentrates.

PMID- 22389134
TI  - Subepithelial trypsin induces enteric nerve-mediated anion secretion by
      activating proteinase-activated receptor 1 in the mouse cecum.
AB  - Serine proteases are versatile signaling molecules and often exert this function
      by activating the proteinase-activated receptors (PAR(1)-PAR(4)). Our previous
      study on the mouse cecum has shown that the PAR(1)-activating peptide (AP) and
      PAR(2)-AP both induced electrogenic anion secretion. This secretion mediated by
      PAR(1) probably occurred by activating the receptor on the submucosal
      secretomotor neurons, while PAR(2)-mediated anion secretion probably occurred by
      activating the receptor on the epithelial cells. This present study was aimed at
      using trypsin to further elucidate the roles of serine proteases and PARs in
      regulating intestinal anion secretion. A mucosal-submucosal sheet of the mouse
      cecum was mounted in Ussing chambers, and the short-circuit current (I(sc)) was
      measured. Trypsin added to the serosal side increased I(sc) with an ED(50) value
      of approximately 100 nM. This I(sc) increase was suppressed by removing Cl(-)
      from the bathing solution. The I(sc) increase induced by 100 nM trypsin was
      substantially suppressed by tetrodotoxin, and partially inhibited by an NK(1)
      receptor antagonist, by a muscarinic Ach-receptor antagonist, and by 5
      hydroxytryptamine-3 (5-HT(3)) and 5-HT(4) receptor antagonists. The I(sc)
      increase induced by trypsin was partially suppressed when the tissue had been
      pretreated with PAR(1)-AP, but not by a pretreatment with PAR(2)-AP. These
      results suggest that the serine protease, trypsin, induced anion secretion by
      activating the enteric secretomotor nerves. This response was initiated in part
      by activating PAR(1) on the enteric nerves. Serine proteases and PARs are likely
      to be responsible for the diarrhea occurring under intestinal inflammatory
      conditions.

PMID- 22389135
TI  - Chronic periodic fluid redistribution effect on muscle calcium in healthy
      subjects during prolonged hypokinesia.
AB  - Studies have shown that chronic periodic fluid shifting upwards is not sensed as
      excessive fluid volume and excretion mechanisms are not activated. To determine
      if chronic periodic fluid and volume shifting upwards can affect muscle calcium
      (Ca(2+)) during hypokinesia (HK) we measured muscle Ca(2+) content, plasma Ca(2+)
      concentration, and Ca(2+) losses in urine and feces. Studies were conducted on 40
      healthy male volunteers. They were divided into four equal groups: active control
      subjects (ACS), hypokinetic subjects (HKS), periodic fluid redistribution control
      subjects (PFRCS), and periodic fluid redistribution hypokinetic subjects (PFRHS).
      Plasma Ca(2+) level decreased (p < 0.05) in Ca(2+) repleted muscle, muscle Ca(2+)
      level increased (p < 0.05), and Ca(2+) losses in urine and feces decreased (p <
      0.05) in the PFRHS group compared with the HKS group. Plasma Ca(2+) level
      increased (p < 0.05) in Ca(2+) deficient muscle, muscle Ca(2+) level decreased (p
      < 0.05), and Ca(2+) losses in urine and feces increased (p < 0.05) in the HKS
      group compared with their pre-experimental levels and the values in their
      respective control groups (ACS and PFRCS). This study shows that the muscle
      Ca(2+) content increases and Ca(2+) excretion decreases, suggesting the clinical
      potential of chronic periodic fluid and volume redistribution in treatment of
      muscle Ca(2+) deficiency.

PMID- 22389136
TI  - Randomized clinical trial comparing infrahepatic inferior vena cava clamping with
      low central venous pressure in complex liver resections involving the Pringle
      manoeuvre.
AB  - BACKGROUND: Control of bleeding remains key to successful hepatic resection. The
      present randomized clinical trial compared infrahepatic inferior vena cava (IVC)
      clamping with low central venous pressure (CVP) during complex hepatectomy using
      portal triad clamping (PTC). METHODS: Consecutive patients undergoing complex
      hepatectomy were allocated randomly to PTC combined with infrahepatic IVC
      clamping or to PTC with low CVP. Primary outcome was blood loss during
      parenchymal transection. Secondary outcomes were intraoperative surgical and
      haemodynamic parameters, postoperative recovery of liver and renal function,
      postoperative morbidity and mortality, and duration of hospital stay. RESULTS:
      Between January 2008 and September 2010, 192 patients were randomized. Compared
      with low CVP, infrahepatic IVC clamping significantly decreased blood loss during
      parenchymal transection (mean(s.e.m.) 243(158) versus 372(197) ml; P < 0.001),
      was associated with faster recovery of liver function, and caused less impairment
      in renal function and fewer haemodynamic changes. The degree of cirrhosis
      correlated positively with CVP (R(2) = 0.963, P = 0.019) and with infrahepatic
      IVC pressure (R(2) = 0.950, P = 0.025). For patients with moderate or severe
      cirrhosis, infrahepatic IVC clamping was more efficacious in controlling blood
      loss during parenchymal transection (mean(s.e.m.) 2.9(1.8) versus 6.1(2.4)
      ml/cm(2); P < 0.001). CONCLUSION: PTC combined with infrahepatic IVC clamping is
      more efficacious in controlling bleeding during complex hepatectomy than PTC with
      low CVP, especially in patients with moderate to severe cirrhosis. REGISTRATION
      NUMBER: NCT01355887 (http://www.clinicaltrials.gov).

PMID- 22389137
TI  - Can chest X ray confirm the right position of the central venous catheter?

PMID- 22389138
TI  - Intraoperative MRI electrical noise and monitor ECG filters affect arrhythmia
      detection and identification.
AB  - Most electrical equipment in the modern operating room (OR) radiates electrical
      noise (EN) that can interfere with patient monitors. We have described the EN
      that an intraoperative magnetic resonance imaging (iMRI) system emits and have
      shown that this high-energy EN diminishes the quality of the ECG waveform during
      iMRI scans in our neurosurgical OR. We have also shown that the ECG signal
      filters in our iMRI-compatible patient monitor reduce this interference but, in
      the process, disturb the true morphology of the displayed waveform. This
      simulation study evaluates how iMRI-generated EN affects the ability of the
      anesthetist to detect and identify ECG arrhythmias and whether the patient
      monitor's ECG signal filters can improve arrhythmia recognition. Using an ECG
      simulator, we generated Lead II and V5 ECG signal segments that contained either
      no arrhythmia or one of four common cardiac arrhythmias. We filtered the ECG
      segments with four filters available on our iMRI-compatible monitor (Veris MR,
      MEDRAD Inc., Indianola, PA USA). We then digitized the segments and mixed
      simulated iMRI EN into the resultant tracings. With institutional approval and
      written informed consent, board-certified anesthesiologists reviewed the
      tracings, determined if an arrhythmia was present and identified the arrhythmia.
      We conducted the study anonymously. We reported the data as percent correct
      arrhythmia detection and correct arrhythmia identification. Thirty-one
      anesthesiologists completed the study. Overall, the participants correctly
      detected 79.5% (95% CI: 77.2, 81.7%) of the arrhythmias and correctly identified
      62.5% (95% CI: 59.8, 65.3%) of the arrhythmias, regardless of EN presence.
      Although the proportions among monitor noise filters studied were not
      significant, the manufacturer-designated MR5 Veris MR filter optimized arrhythmia
      detection and arrhythmia identification for our participants, regardless if EN
      was present in the ECG tracings. In the neurosurgical OR, the anesthetist must be
      able to effectively monitor a patient in the presence of iMRI-generated EN.
      Depending on the OR design, the patient may be out of the anesthetist's direct
      view during a scan procedure. The anesthetist must rely on monitored physiologic
      parameters to assess patient status during this time. He/she should be familiar
      with his/her monitor's filtering capabilities and routinely adjust the ECG
      filters to achieve the best compromise between minimized EN effects and maximized
      displayed ECG signal quality.

PMID- 22389139
TI  - Allopurinol attenuates left ventricular dysfunction in rats with early stages of
      streptozotocin-induced diabetes.
AB  - BACKGROUND: Xanthine oxidase-derived superoxide production and oxidative stress
      contribute to the development of diabetic complications including diabetic
      cardiomyopathy. We hypothesized that xanthine oxidase-inhibitor allopurinol (ALP)
      may decrease hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte
      hypertrophy and fibrosis, and attenuate the development of left ventricle (LV)
      diastolic dysfunction in rats with streptozotocin (STZ)-induced diabetes.
      METHODS: Control Sprague Dawley (C) or streptozotocin-induced diabetic (D) rats
      were either untreated or treated with allopurinol (100 mg/kg/day) for 4 weeks
      starting at 1 week after streptozotocin injection. Free 15-F2t-isoprostane, a
      specific indicator of oxidative stress was measured by enzymatic immunoassay. The
      cardiomyocyte cross-sectional area was assessed by hematoxylin and eosin-stained
      paraffin-embedded sections of LVs. Myocardial collagens I and III were assessed
      by immunol histochemistry and Western blotting. Echocardiography was performed to
      characterize cardiac structure and function. RESULTS: In diabetic rats, both
      plasma and cardiac tissue levels of free 15-F2t-isoprostane were increased (p <
      0.05 vs. control), accompanied with significant increase (p < 0.05 vs. control)
      in cross-section area and myocardial collagen deposition of LV cardiomyocyte.
      Echocardiography in diabetic rats showed that LV weight/body weight ratio was
      significantly higher than in control rats, whereas the levels of LV end-diastolic
      volume and stroke volume were decreased (all p < 0.05 diabetic vs. control). All
      these changes were either attenuated or prevented by allopurinol. In addition, LV
      ejection fraction in diabetic rats treated with allopurinol was higher than that
      in untreated diabetic rats (p < 0.05). CONCLUSION: Allopurinol can attenuate
      hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte hypertrophy and
      fibrosis and subsequently prevent left ventricular dysfunction in early diabetes.

PMID- 22389140
TI  - Set-up errors and planning target volume margins in head and neck cancer
      radiotherapy: a clinical study of image guidance with on-line cone-beam computed
      tomography.
AB  - BACKGROUND: Set-up errors represent a source of uncertainty in head and neck
      (H&N) cancer radiotherapy. The present study evaluated set-up accuracy with the
      use of cone-beam computed tomography (CBCT) in order to establish the proper
      clinical target volume (CTV) to planning target volume (PTV) margins to be
      adopted. METHODS: Local set-up accuracy was analysed for 44 H&N cancer patients
      since the implementation of CBCT. An on-line correction protocol was adopted,
      with the first 3 scans used to correct systematic errors with a 3-mm action
      level. The overall mean displacement (M), the population systematic (Sigma) and
      random (sigma) errors and the 3D vector length were calculated. PTV margins were
      calculated according to the van Herk formula (2.5Sigma + 0.7sigma). RESULTS: A
      total of 420 CBCT scans were analysed. A systematic correction was needed in 43%
      of patients. The value of M was <1 mm in all directions; the values of Sigma and
      sigma ranged over 1-1.2 and 1.4-1.9 mm, respectively. Pre-correction PTV margins
      were 3.48, 4.08 and 4.33 mm along the 3 axes. The PTV margins calculated after
      online correction were <2.5 mm in all directions. CONCLUSIONS: Kilovoltage CBCT
      is effective in evaluating set-up accuracy in H&N patients. CTV-PTV margins of 5
      mm are safe and are currently adopted at our centre; however, some special
      situations, such as re-irradiation or the close proximity of organs at risk and
      high-dose regions, could benefit from daily image registration and lower (i.e., 3
      mm) margins.

PMID- 22389141
TI  - Synchrony dynamics across brain structures in limbic epilepsy vary between
      initiation and termination phases of seizures.
AB  - Neuronal populations in the brain achieve levels of synchronous
      electrophysiological activity during both normal brain function and pathological
      states such as epileptic seizures. Understanding how the dynamics of neuronal
      oscillators in the brain evolve from normal to diseased states is a critical
      component toward decoding such complex behaviors. In this study, we sought to
      develop a more in-depth understanding of multisite dynamics underlying seizure
      evolution in limbic epilepsy by analyzing oscillators in recordings of local
      field potentials from three brain structures (bilateral hippocampi and
      anteromedial thalamus) in a kainic acid in vivo rat model of temporal lobe
      epilepsy extracted using the empirical mode decomposition (EMD) technique. EMD
      provides an adaptive nonlinear decomposition into a set of finite oscillatory
      components. Oscillator frequencies, power, and phase synchrony were assessed
      within and between sites as seizures evolved. Consistent patterns of low
      frequency (~35 Hz) synchrony occurred transiently during early-stage ictogenesis
      between thalamus and both hippocampi; in contrast, higher frequency (~120 Hz)
      synchrony appeared between thalamus and focal hippocampus as seizures naturally
      terminated. These multi-site synchrony events may provide a key insight into how
      synchrony disruption via stimulation could be targeted as well as contribute to a
      better understanding of how brain synchrony evolves in epilepsy.

PMID- 22389142
TI  - US-fluoroscopy registration for transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation is a minimally invasive alternative to
      open-heart surgery for aortic stenosis in which a stent-based bioprosthetic valve
      is delivered into the heart on a catheter. Limited visualization during this
      procedure can lead to severe complications. Improved visualization can be
      provided by live registration of transesophageal echo (TEE) and fluoroscopy
      images intraoperatively. Since the TEE probe is always visible in the fluoroscopy
      image, it is possible to track it using fiducial-based single-perspective pose
      estimation. In this study, inherent probe tracking performance was assessed, and
      TEE to fluoroscopy registration accuracy and robustness were evaluated. Results
      demonstrated probe tracking errors of below 0.6 mm and 0.2 degrees , a 2-D RMS
      registration error of 1.5 mm, and a tracking failure rate of below 1%. In
      addition to providing live registration and better accuracy and robustness
      compared to existing TEE probe tracking methods, this system is designed to be
      suitable for clinical use. It is fully automatic, requires no additional
      operating room hardware, does not require intraoperative calibration, maintains
      existing procedure and imaging workflow without modification, and can be
      implemented in all cardiac centers at extremely low cost.

PMID- 22389144
TI  - Interpolation-based image super-resolution using multisurface fitting.
AB  - In this paper, we propose a new interpolation-based method of image super
      resolution reconstruction. The idea is using multisurface fitting to take full
      advantage of spatial structure information. Each site of low-resolution pixels is
      fitted with one surface, and the final estimation is made by fusing the
      multisampling values on these surfaces in the maximum a posteriori fashion. With
      this method, the reconstructed high-resolution images preserve image details
      effectively without any hypothesis on image prior. Furthermore, we extend our
      method to a more general noise model. Experimental results on the simulated and
      real-world data show the superiority of the proposed method in both quantitative
      and visual comparisons.

PMID- 22389143
TI  - Anticancer drugs from traditional toxic Chinese medicines.
AB  - Many anticancer drugs are obtained from natural sources. Nature produces a
      variety of toxic compounds, which are often used as anticancer drugs. Up to now,
      there are at least 120 species of poisonous botanicals, animals and minerals, of
      which more than half have been found to possess significant anticancer
      properties. In spite of their clinical toxicity, they exhibit pharmacological
      effects and have been used as important traditional Chinese medicines for the
      different stages of cancer. The article reviews many structures such as alkaloids
      of Camptotheca acuminata, Catharanthus roseus and Cephalotaxus fortunei, lignans
      of Dysosma versipellis and Podophyllum emodi, ketones of Garcinia hanburyi,
      terpenoids of Mylabris and Ginkgo biloba, diterpenoids of Tripterygium wilfordii,
      Euphorbia fischeriana, Euphorbia lathyris, Euphorbia kansui, Daphne genkwa,
      Pseudolarix kaempferi and Brucea javanica, triterpenoids of Melia toosendan,
      steroids of Periploca sepium, Paris polyphylla and Venenum Bufonis, and arsenic
      compounds including Arsenicum and Realgar. By comparing their related
      phytochemistry, toxic effects and the recent advances in understanding the
      mechanisms of action, this review puts forward some ideals and examples about how
      to increase antitumour activity and/or reduce the side effects experienced with
      Chinese medicine.

PMID- 22389145
TI  - Cognition and removal of impulse noise with uncertainty.
AB  - Uncertainties are the major inherent feature of impulse noise. This fact makes
      image denoising a difficult task. Understanding the uncertainties can improve the
      performance of image denoising. This paper presents a novel adaptive detail
      preserving filter based on the cloud model (CM) to remove impulse noise. It is
      called the CM filter. First, an uncertainty-based detector identifies the pixels
      corrupted by impulse noise. Then, a weighted fuzzy mean filter is applied to
      remove the noise candidates. The experimental results show that, compared with
      the traditional switching filters, the CM filter makes a great improvement in
      image denoising. Even at a noise level as high as 95%, the CM filter still can
      restore the image with good detail preservation.

PMID- 22389146
TI  - Posterior-mean super-resolution with a causal Gaussian Markov random field prior.
AB  - We propose a Bayesian image super-resolution (SR) method with a causal Gaussian
      Markov random field (MRF) prior. SR is a technique to estimate a spatially high
      resolution image from given multiple low-resolution images. An MRF model with the
      line process supplies a preferable prior for natural images with edges. We
      improve the existing image transformation model, the compound MRF model, and its
      hyperparameter prior model. We also derive the optimal estimator--not the joint
      maximum a posteriori (MAP) or the marginalized maximum likelihood (ML) but the
      posterior mean (PM)--from the objective function of the L2-norm-based (mean
      square error) peak signal-to-noise ratio. Point estimates such as MAP and ML are
      generally not stable in ill-posed high-dimensional problems because of
      overfitting, whereas PM is a stable estimator because all the parameters in the
      model are evaluated as distributions. The estimator is numerically determined by
      using the variational Bayesian method. The variational Bayesian method is a
      widely used method that approximately determines a complicated posterior
      distribution, but it is generally hard to use because it needs the conjugate
      prior. We solve this problem with simple Taylor approximations. Experimental
      results have shown that the proposed method is more accurate or comparable to
      existing methods.

PMID- 22389147
TI  - Perceptual strength of 3-D crosstalk in both achromatic and color images in
      stereoscopic 3-D displays.
AB  - The cognitive strength of crosstalk in stereoscopic 3-D displays is investigated,
      and new quantitative analysis methods based on color difference and grayscale
      levels are developed. Unlike results using existing metrics, results by the new
      methods agree well with the perceived crosstalk strength in achromatic images
      with various levels of grayscale. The crosstalk in color images, which has not
      been studied before, exhibits interesting results in that the crosstalk metric
      based on the lightness difference expresses the best fit with the perceptual
      crosstalk when the intended image is black and the chroma value of the
      counterpart image is large, but the metric using the color difference works
      better when the intended image is not black. The new metrics reveal that the
      difference between active and passive 3-D displays is not as large as suggested
      by conventional crosstalk metrics, and the crosstalk in color images cannot be
      simply estimated by averaging the crosstalk of red, green, and blue subpixels.
      The new metrics will be useful in the development of new image processing
      technology and display technology for better image quality.

PMID- 22389148
TI  - Robust tracking with discriminative ranking lists.
AB  - In this paper, we propose a novel tracking algorithm, i.e., the discriminative
      ranking list-based tracker (DRLTracker). The DRLTracker models the target object
      and its local background by using ranking lists of patches of different scales
      within object bounding boxes. The ranking list of each of such patches is its  K
      nearest neighbors. Patches of the same scale with ranking lists of high purity
      values (meaning high probabilities to be on the target object) and some
      confusable background patches constitute the object model under that scale. A
      pair of object models of two different scales collaborate to determine which
      patches may belong to the target object in the next frame. The DRLTracker can
      effectively alleviate the distraction problem, and its superior ability over
      several representative and state-of-the-art trackers is demonstrated through
      extensive experiments.

PMID- 22389149
TI  - Simulated infrared spectra of triflic acid during proton dissociation.
AB  - Vibrational analysis of triflic acid (TfOH) at different water uptakes was
      conducted. This molecule mimics the sulfonate end of the Nafion side-chain. As
      the proton leaves the sulfonic acid group, structural changes within the Nafion
      side-chain take place. They are revealed by signal shifts in the infrared
      spectrum. Molecular modeling is used to follow structural modifications that
      occur during proton dissociation. To confirm the accuracy of the proposed
      structures, infrared spectra were computed via quantum chemical modeling based on
      density functional theory. The requirement to use additional diffuse functions in
      the basis set is discussed. Comparison between simulated infrared spectra of 1
      and 2 acid molecules with different water contents and experimental data was
      performed. An accurate description of infrared spectra for systems containing 2
      TfOH was obtained.

PMID- 22389150
TI  - Alignment in interactive reference production: content planning, modifier
      ordering, and referential overspecification.
AB  - Psycholinguistic studies often look at the production of referring expressions in
      interactive settings, but so far few referring expression generation algorithms
      have been developed that are sensitive to earlier references in an interaction.
      Rather, such algorithms tend to rely on domain-dependent preferences for both
      content selection and linguistic realization. We present three experiments
      showing that humans may opt for dispreferred attributes and dispreferred modifier
      orderings when these were primed in a preceding interaction (without speakers
      being consciously aware of this). In addition, we show that speakers are more
      likely to produce overspecified references, including dispreferred attributes
      (although minimal descriptions with preferred attributes would suffice), when
      these were similarly primed.

PMID- 22389151
TI  - NMR-spectroscopic evidence of intermediate-dependent pathways for acetic acid
      formation from methane and carbon monoxide over a ZnZSM-5 zeolite catalyst.
AB  - Two ways: a Zn-modified ZSM-5 zeolite catalyst was developed for the reaction of
      methane with carbon monoxide to directly produce acetic acid under mild
      conditions (573-623 K), and two different intermediate-dependent reaction
      pathways were unambiguously identified for acetic acid formation by in situ solid
      state NMR spectroscopy.

PMID- 22389153
TI  - Dynamic Features for Iris Recognition.
AB  - The human eye is sensitive to visible light. Increasing illumination on the eye
      causes the pupil of the eye to contract, while decreasing illumination causes the
      pupil to dilate. Visible light causes specular reflections inside the iris ring.
      On the other hand, the human retina is less sensitive to near infra-red (NIR)
      radiation in the wavelength range from 800 nm to 1400 nm, but iris detail can
      still be imaged with NIR illumination. In order to measure the dynamic movement
      of the human pupil and iris while keeping the light-induced reflexes from
      affecting the quality of the digitalized image, this paper describes a device
      based on the consensual reflex. This biological phenomenon contracts and dilates
      the two pupils synchronously when illuminating one of the eyes by visible light.
      In this paper, we propose to capture images of the pupil of one eye using NIR
      illumination while illuminating the other eye using a visible-light pulse. This
      new approach extracts iris features called "dynamic features (DFs)." This
      innovative methodology proposes the extraction of information about the way the
      human eye reacts to light, and to use such information for biometric recognition
      purposes. The results demonstrate that these features are discriminating
      features, and, even using the Euclidean distance measure, an average accuracy of
      recognition of 99.1% was obtained. The proposed methodology has the potential to
      be "fraud-proof," because these DFs can only be extracted from living irises. 

PMID- 22389152
TI  - Hinfinity State Estimation for Discrete-Time Chaotic Systems Based on a Unified
      Model.
AB  - This paper is concerned with the problem of state estimation for a class of
      discrete-time chaotic systems with or without time delays. A unified model
      consisting of a linear dynamic system and a bounded static nonlinear operator is
      employed to describe these systems, such as chaotic neural networks, Chua's
      circuits, Henon map, etc. Based on the Hinfinity performance analysis of this
      unified model using the linear matrix inequality approach, Hinfinity state
      estimator are designed for this model with sensors to guarantee the asymptotic
      stability of the estimation error dynamic systems and to reduce the influence of
      noise on the estimation error. The parameters of these filters are obtained by
      solving the eigenvalue problem. As most discrete-time chaotic systems with or
      without time delays can be described with this unified model, Hinfinity state
      estimator design for these systems can be done in a unified way. Three numerical
      examples are exploited to illustrate the effectiveness of the proposed estimator
      design schemes. 

PMID- 22389154
TI  - Dose evaluation in criticality accidents using response of Panasonic TL personal
      dosemeters (UD-809/UD-802).
AB  - This study gives the results of dosimetry measurements carried out in the Silene
      reactor at Valduc (France) with neutron and photon personal thermoluminescence
      dosemeters (TLDs) in mixed neutron and gamma radiation fields, in the frame of
      the international accident dosimetry intercomparison programme in 2002. The
      intercomparison consisted of a series of three irradiation scenarios. The
      scenarios took place at the Valduc site (France) by using the Silene experimental
      reactor. For neutron and photon dosimetry, Panasonic model UD-809 and UD-802
      personal TLDs were used together.

PMID- 22389155
TI  - Toward multiple catheters detection in fluoroscopic image guided interventions.
AB  - Catheters are routinely inserted via vessels to cavities of the heart during
      fluoroscopic image guided interventions for electrophysiology (EP) procedures
      such as ablation. During such interventions, the catheter undergoes nonrigid
      deformation due to physician interaction, patient's breathing, and cardiac
      motions. EP clinical applications can benefit from fast and accurate automatic
      catheter tracking in the fluoroscopic images. The typical low quality in
      fluoroscopic images and the presence of other medical instruments in the scene
      make the automatic detection and tracking of catheters in clinical environments
      very challenging. Toward the development of such an application, a robust and
      efficient method for detecting and tracking the catheter sheath is developed. The
      proposed approach exploits the clinical setup knowledge to constrain the search
      space while boosting both tracking speed and accuracy, and is based on a
      computationally efficient framework to trace the sheath and simultaneously detect
      one or multiple catheter tips. The algorithm is based on a modification of the
      fast marching weighted distance computation that efficiently calculates, on the
      fly, important geodesic properties in relevant regions of the image. This is
      followed by a cascade classifier for detecting the catheter tips. The proposed
      technique is validated on 1107 fluoroscopic images acquired on multiple patients
      across four different clinics, achieving multiple catheter tracking at a rate of
      10 images/s with a very low false positive rate of 1.06.

PMID- 22389156
TI  - A state-of-the-art review on segmentation algorithms in intravascular ultrasound
      (IVUS) images.
AB  - Over the past two decades, intravascular ultrasound (IVUS) image segmentation has
      remained a challenge for researchers while the use of this imaging modality is
      rapidly growing in catheterization procedures and in research studies. IVUS
      provides cross-sectional grayscale images of the arterial wall and the extent of
      atherosclerotic plaques with high spatial resolution in real time. In this paper,
      we review recently developed image processing methods for the detection of media
      adventitia and luminal borders in IVUS images acquired with different transducers
      operating at frequencies ranging from 20 to 45 MHz. We discuss methodological
      challenges, lack of diversity in reported datasets, and weaknesses of
      quantification metrics that make IVUS segmentation still an open problem despite
      all efforts. In conclusion, we call for a common reference database, validation
      metrics, and ground-truth definition with which new and existing algorithms could
      be benchmarked.

PMID- 22389157
TI  - Semantic image retrieval in magnetic resonance brain volumes.
AB  - Practitioners in the area of neurology often need to retrieve multimodal magnetic
      resonance (MR) images of the brain to study disease progression and to correlate
      observations across multiple subjects. In this paper, a novel technique for
      retrieving 2-D MR images (slices) in 3-D brain volumes is proposed. Given a 2-D
      MR query slice, the technique identifies the 3-D volume among multiple subjects
      in the database, associates the query slice with a specific region of the brain,
      and retrieves the matching slice within this region in the identified volumes.
      The proposed technique is capable of retrieving an image in multimodal and noisy
      scenarios. In this study, support vector machines (SVM) are used for identifying
      3-D MR volume and for performing semantic classification of the human brain into
      various semantic regions. In order to achieve reliable image retrieval
      performance in the presence of misalignments, an image registration-based
      retrieval framework is developed. The proposed retrieval technique is tested on
      various modalities. The test results reveal superior robustness performance with
      respect to accuracy, speed, and multimodality.

PMID- 22389158
TI  - Chronic kidney disease prevention--a challenge for Asian countries: report of the
      Third Asian Forum of Chronic Kidney Disease Initiatives.
AB  - As an independent meeting, the third Asian Forum of Chronic Kidney Disease
      Initiatives was held on April 18-19, 2009, in Kaohsiung, Taiwan. Nearly 700
      participants from 17 countries attended and 78 posters were presented. To begin
      with, status quo in Asia and in Taiwan was briefed, followed by Theme 1A "Special
      Epidemiology and Risk Factors", during which the interrelations between chronic
      kidney disease (CKD) and use of herbs, low birth weight, infections, and
      immunoglobulin A (IgA) nephropathy were discussed. Theme 1B dealt with both
      cardiovascular and renal outcomes of CKD patients. In Theme 2, five presenters
      from different countries shared their experiences on "Cost-effectiveness of
      Community-based or Nationwide CKD Prevention Programs". In between the conference
      themes, three international and integrative works--Kidney Disease Improving
      Global Outcomes, the World Kidney Day, and Kidney Early Evaluation Program--were
      presented and possible implications for Asia were suggested. Theme 3 was
      initiated with a thorough discussion on "Equation of the Estimated Glomerular
      Filtration Rate for Asians" and the preliminary results of a cross-country study
      were presented. In Theme 4, the care plan, strategies, and outcomes of timely
      initiation of dialysis in different countries were discussed. The final session
      started with a concise summary of all speeches and ended with a position
      statement.

PMID- 22389159
TI  - The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal
      squamous cell carcinoma cells to nimotuzumab combined with cisplatin.
AB  - Nimotuzumab is an antibody against epidermal growth factor receptor (EGFR). The
      objective of this study was to examine the capacity and specific underlying
      mechanisms of nimotuzumab to modulate cytotoxicity of cisplatin (DDP) in
      esophageal squamous cell carcinoma (ESCC) cell lines with different EGFR
      expression levels. Nimotuzumab was administrated to two ESCC cell lines KYSE30
      and TE-1 treated with DDP. Cell growth, colony formation, and apoptosis were
      analyzed by MTT and flow cytometry assays. The method of RNA interference was
      used to investigate the role of insulin-like growth factor binding protein-3
      (IGFBP-3) in ESCC cells chemosensitivity treated with nimotuzumab. Combination of
      nimotuzumab and DDP resulted in a DDP cytotoxicity increase in overexpressing
      EGFR cells (KYSE30) but not in low-expressing EGFR cells (TE-1). Meantime, DDP
      activated the EGFR pathway in the two cell lines in a ligand-independent fashion.
      Furthermore, DDP-induced EGFR activation was inhibited by nimotuzumab in KYSE30
      cells, and this result was not observed in TE-1 cells. EGF reduced the expression
      of IGFBP-3 in KYSE30 cells; however, nimotuzumab could reverse the downregulation
      of IGFBP-3, and this result was also not observed in TE-1 cells. After IGFBP-3
      was silenced by small interfering RNA, the potential of nimotuzumab to enhance
      DDP-mediated cytotoxicity was inhibited in KYSE30 cells. The results indicated
      that the increased ESCC chemosensitivity to DDP by nimotuzumab might be dependent
      on IGFBP-3 upregulation through EGFR-dependent pathway, which would facilitate
      preselection of ESCC patients for treatment of nimotuzumab combined with DDP.

PMID- 22389161
TI  - Survivors advocate for cancer research and patients: these advocates offer a
      unique perspective when communicating with lawmakers, care providers, and the
      scientific community.

PMID- 22389160
TI  - Dosimetry results suggest feasibility of radioimmunotherapy using anti-CD138 (B
      B4) antibody in multiple myeloma patients.
AB  - Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on
      tumor cells in multiple myeloma (MM). This surface antigen is an attractive
      candidate for targeted therapy, especially radioimmunotherapy (RAIT). We report
      preliminary biodistribution and dosimetry results obtained in refractory MM
      patients in a phase I/II RAIT study using iodine-131-labeled anti-CD138 (B-B4)
      monoclonal antibody (mAb). Four patients with progressive disease were enrolled
      after three lines of therapy. They received 370 MBq (20 mg/m(2)) of (131)I-B-B4
      for the dosimetry study. Each patient underwent a whole body (WB) CT and four WB
      emission scans at days D0, D1, and D3-4. Images were corrected for attenuation
      and scatter to assess doses absorbed by organs and bone marrow (BM). Blood and
      urine samples were additionally collected. Dosimetry was conducted using the MIRD
      method. Images obtained 1 h after (131)I-B-B4 injection showed high BM and liver
      uptake without kidney uptake. The BM uptake confirmed BM involvement as detected
      by pre-inclusion FDG PET/CT. Absorbed doses were calculated at 2.03 +/- 0.3
      mGy/MBq for the liver, 1.10 +/- 0.9 mGy/MBq for the kidneys, and 0.52 +/- 0.20
      mGy/MBq for the BM. Grade III thrombocytopenia was documented in two cases
      (highest BM-absorbed doses), and no grade IV hematological toxicity was observed.
      Therefore, autologous stem cells were not infused. One patient out of four
      experienced partial response, with 60% reduction of M-spike on serum
      electrophoresis, and total relief of pain, lasting for 1 year. This patient was
      able to go back to work. In this proof of concept study based on dosimetry, we
      show that MM RAIT is feasible using the anti-CD138 antibody. It would be of great
      interest to perform a RAIT phase I/II trial with a humanized anti-CD138 mAb with
      increased doses and systematic autologous stem cell infusions to overcome
      hematological toxicity and achieve efficacy.

PMID- 22389162
TI  - A case for annual mammography screening.

PMID- 22389163
TI  - Behavioral sleep problems in children and adolescents.
AB  - Sleep problems in children and adolescents are common, and they impact multiple
      domains of child and family functioning. Psychologists have a critical role in
      the assessment and treatment of sleep problems and are integral to
      interdisciplinary sleep teams. Certain sleep problems may be related to co-morbid
      psychological or developmental conditions, and others are considered to be
      primarily medical, yet behavioral approaches may be applicable. There are also
      sleep problems considered to be behavioral in etiology (e.g. inadequate sleep
      hygiene, behavioral insomnia of childhood, nightmares/bad dreams/nighttime fears,
      delayed sleep phase syndrome, and psychophysiological insomnia). In this article,
      the assessment of behavioral sleep problems, as well as specific behavioral sleep
      disorders, and their treatments will be discussed.

PMID- 22389164
TI  - Larvicidal activity of Cnidium monnieri fruit coumarins and structurally related
      compounds against insecticide-susceptible and insecticide-resistant Culex pipiens
      pallens and Aedes aegypti.
AB  - BACKGROUND: An assessment was made of the toxicity of imperatorin and osthole
      identified in Cnidium monnieri fruit, 11 related compounds and five insecticides
      to larvae from insecticide-susceptible Culex pipiens pallens (KS-CP strain) and
      Aedes aegypti and wild C.p. pallens (YS-CP colony) using a direct-contact
      mortality bioassay. Results were compared with those of the conventional
      larvicide temephos. RESULTS: Imperatorin (LC(50) = 3.14 and 2.88 mg L(-1) ) was
      1.9-, 3.7- and 4.2-fold and 2.4-, 4.5- and 4.6-fold more toxic than
      isopimpinellin, isoimperatorin and osthole against susceptible C. p. pallens and
      A. aegypti larvae respectively. Overall, all of the compounds were less toxic
      than temephos (0.011 and 0.019 mg L(-1) ). The toxicity of these compounds was
      virtually identical against larvae from the two Culex strains, even though YS-CP
      larvae were resistant to fenthion (resistance ratio RR = 390), deltamethrin (RR =
      164), cyfluthrin (RR = 14) and temephos (RR = 14). This finding indicates that
      the coumarins and the insecticides do not share a common mode of action. The
      structure-activity relationship indicates that the chemical structure and alkoxy
      substitution and length of the alkoxyl side chain at the C8 position are
      essential for imparting toxicity. CONCLUSION: The C. monnieri fruit-derived
      coumarins and the related coumarins described merit further study as potential
      insecticides or lead molecules for the control of insecticide-resistant mosquito
      populations.

PMID- 22389165
TI  - Cancer and coagulation.
AB  - Thromboembolism, including both venous and arterial events, occurs commonly
      amongst patients with cancer. The occurrence of thromboembolism has significant
      consequences for cancer patients, including direct and indirect associations with
      mortality, morbidity, requirement for long-term anticoagulant therapy and
      consumption of healthcare resources. Recent studies have resulted in a better
      understanding of clinical risk factors and biomarkers of cancer-associated
      thrombosis, and a risk assessment model incorporating both has now been validated
      in multiple settings. Thromboprophylaxis with either unfractionated heparin or
      low-molecular-weight heparins (LMWHs) has been shown to be safe and effective in
      high-risk settings such as hospitalization for medical illness and the
      postsurgical period. Emerging new data from randomized studies have focused on
      outpatient prophylaxis, suggesting potential benefits in this setting as well.
      Treatment of cancer-associated thrombosis requires long-term anticoagulation with
      LMWH. Results from ongoing and planned trials of novel anticoagulants in the
      cancer setting are awaited.

PMID- 22389166
TI  - Quantitative hippocampal structural changes following electroconvulsive seizure
      treatment in a rat model of depression.
AB  - OBJECTIVE: The pathophysiology of depression and the effects of antidepressant
      treatment are hypothesized to be related to hippocampal structural changes. This
      study aims to investigate the effect of electroconvulsive seizures on behavior
      and hippocampal structure in a rat model of depression. METHODS: Flinders
      Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were treated daily
      for 10 days with either electroconvulsive seizures or sham treatment. The
      behavior was evaluated using the forced swim test. Design-based stereological
      methods were used to quantify the hippocampal volume and the numbers of neurons
      and glial cells in specific hippocampal subregions. RESULTS: The basal level of
      hippocampal volume and neuron number differed significantly between the two rat
      strains, and a trend toward the FSL strain having more glial cells was found. The
      structural differences found between the sham-treated animals were counteracted
      by electroconvulsive seizure (ECS) treatment, which also normalized the behavior.
      ECS treatment increased the number of glial cells in hilus significantly in the
      FRL rats and with the same tendency for the FSL rats. CONCLUSION: Our results
      indicate that along with hippocampal neurogenesis, gliogenesis may also be
      involved in the pathophysiology of depression and in the effect of antidepressant
      treatment. The underlying mechanisms remain unknown, and further investigations
      are required to clarify whether the structural changes are necessary to induce a
      therapeutic effect of antidepressant treatment or if they rather represent an
      epiphenomenon.

PMID- 22389168
TI  - Total synthesis of homogeneous antifreeze glycopeptides and glycoproteins.

PMID- 22389169
TI  - An asymmetric oligomer based on thienoacene for solution processed crystal
      organic thin-film transistors.
AB  - A novel thienoacene-based conjugated oligomer, i.e.BTTT-T-C12, was designed and
      synthesized. Its highly asymmetric structural feature enables the preparation of
      two-dimensional single-crystalline thin films in millimetre size and ~100 nm
      thick by a solution processing method directly on the Si/SiO(2) substrate. Single
      crystal organic thin film transistors exhibit a mobility of 0.70 cm(2) V(-1) s(
      1) and an on/off ratio of 5.7 * 10(4).

PMID- 22389167
TI  - Safflower seed extract inhibits osteoclast differentiation by suppression of the
      p38 mitogen-activated protein kinase and IkappaB kinase activity.
AB  - Safflower seed has been reported to have a protective effect against bone loss
      diseases. However, the precise molecular mechanisms underlying the inhibitory
      effect of safflower seed in osteoclast differentiation remain unclear. In this
      study, we investigated the inhibitory action of safflower seed extract (SSE) on
      the receptor activator of nuclear factor kappaB ligand (RANKL)-induced
      osteoclastogenesis in cultured mouse-derived bone marrow macrophages (BMMs). We
      found that SSE significantly inhibited the formation of tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells in BMMs without cytotoxicity.
      The gene expressions of nuclear factor of activated T-cells (NFATc1) and TRAP,
      which are genetic markers of osteoclast differentiation, were substantially
      decreased by SSE in a dose-dependent manner. Also, SSE diminished RANKL-mediated
      intracellular reactive oxygen species (ROS) generation on osteoclastogenesis in a
      dose-dependent manner. The SSE thereafter suppressed RANKL-induced p38 mitogen
      activated protein kinase and IkappaBalpha kinase signalling activities which were
      activated by ROS generation for osteoclastogenesis. Additionally, SSE was found
      to decrease RANKL-induced actin ring formation, which is required for bone
      resorption activity. Taken together, our results suggest that SSE acts as a RANKL
      induced osteoclastogenesis inhibitor by suppression of ROS generation. This
      induces a remarkable suppression of the p38 and IkappaBalpha kinase pathways,
      thereby suppressing the gene expression of NFATc1 in osteoclast precursors.

PMID- 22389170
TI  - Toward a computational psycholinguistics of reference production.
AB  - This article introduces the topic ''Production of Referring Expressions: Bridging
      the Gap between Computational and Empirical Approaches to Reference'' of the
      journal Topics in Cognitive Science. We argue that computational and
      psycholinguistic approaches to reference production can benefit from closer
      interaction, and that this is likely to result in the construction of algorithms
      that differ markedly from the ones currently known in the computational
      literature. We focus particularly on determinism, the feature of existing
      algorithms that is perhaps most clearly at odds with psycholinguistic results,
      discussing how future algorithms might include non-determinism, and how new
      psycholinguistic experiments could inform the development of such algorithms.

PMID- 22389172
TI  - A Bayesian approach to the evaluation of comparisons of individually value
      assigned reference materials.
AB  - Several recent international comparison studies used a relatively novel
      experimental design to evaluate the measurement capabilities of participating
      organizations. These studies compared the values assigned by each participant to
      one or more qualitatively similar materials with measurements made on all of the
      materials by one laboratory under repeatability conditions. A statistical model
      was then established relating the values to the repeatability measurements; the
      extent of agreement between the assigned value(s) and the consensus model
      reflected the participants' measurement capabilities. Since each participant used
      their own supplies, equipment, and methods to produce and value-assign their
      material(s), the agreement between the assigned value(s) and the model was a
      fairer reflection of their intrinsic capabilities than provided by studies that
      directly compared time- and material-constrained measurements on unknown samples
      prepared elsewhere. A new statistical procedure is presented for the analysis of
      such data. The procedure incorporates several novel concepts, most importantly a
      leave-one-out strategy for the estimation of the consensus value of the
      measurand, model fitting via Bayesian posterior probabilities, and posterior
      coverage probability calculation for the assigned 95% uncertainty intervals. The
      benefits of the new procedure are illustrated using data from the CCQM-K54
      comparison of eight cylinders of n-hexane in methane.

PMID- 22389173
TI  - Novel approach for the simultaneous detection of DNA from different fish species
      based on a nuclear target: quantification potential.
AB  - The development of DNA-based methods for the identification and quantification of
      fish in food and feed samples is frequently focused on a specific fish species
      and/or on the detection of mitochondrial DNA of fish origin. However, a
      quantitative method for the most common fish species used by the food and feed
      industry is needed for official control purposes, and such a method should rely
      on the use of a single-copy nuclear DNA target owing to its more stable copy
      number in different tissues. In this article, we report on the development of a
      real-time PCR method based on the use of a nuclear gene as a target for the
      simultaneous detection of fish DNA from different species and on the evaluation
      of its quantification potential. The method was tested in 22 different fish
      species, including those most commonly used by the food and feed industry, and in
      negative control samples, which included 15 animal species and nine feed
      ingredients. The results show that the method reported here complies with the
      requirements concerning specificity and with the criteria required for real-time
      PCR methods with high sensitivity.

PMID- 22389171
TI  - A systematic review of large-scale surveys of cancer survivors conducted in North
      America, 2000-2011.
AB  - INTRODUCTION: Many large surveys collect data on cancer survivors, but few
      encompass the full spectrum of domains relevant to survivorship ranging from
      cancer care to quality of life to late- and long-term effects of cancer and its
      treatment. Here, we review large data sources in North America collecting cancer
      survivor-reported health information, and catalogue the domains of cancer
      survivorship each includes. METHODS: We identified surveys of cancer survivors
      through a comprehensive web search of federal government agencies, non-profit
      organizations, and related societies that support health care research or provide
      health care services, as well as a systematic review of literature indexed on
      PubMed from 2000-2011. RESULTS: A total of 57 surveys were identified, 26
      nationally representative surveys and 31 regional, state, or provincial surveys.
      Thirty-four surveys specifically targeted cancer survivors, and an additional two
      surveys had supplements or modules targeted at cancer survivors. Among the
      nationally representative surveys, general medical characteristics and medical
      conditions were the most frequently reported cancer survivorship domains, and
      information on cancer-related costs was least frequently reported.
      DISCUSSION/CONCLUSION: Our review demonstrates that a large and growing number of
      surveys across the U.S. and Canada are collecting data on cancer survivors. These
      surveys differ in design, geographic region, primary population of interest,
      cancer site, and research areas of interest. They address a wide range of
      survivorship issues. Future cancer survivorship research should concentrate on
      understudied areas in order to better understand the challenges faced by this
      growing population.

PMID- 22389174
TI  - Small--smaller--MUTAS.

PMID- 22389175
TI  - Investigation of the chemical composition-antibacterial activity relationship of
      essential oils by chemometric methods.
AB  - The antibacterial effects of Thymus vulgaris (Lamiaceae), Lavandula angustifolia
      (Lamiaceae), and Calamintha nepeta (Lamiaceae) Savi subsp. nepeta var.
      subisodonda (Borb.) Hayek essential oils on five different bacteria were
      estimated. Laboratory control strain and clinical isolates from different
      pathogenic media were researched by broth microdilution method, with an emphasis
      on a chemical composition-antibacterial activity relationship. The main
      constituents of thyme oil were thymol (59.95%) and p-cymene (18.34%). Linalool
      acetate (38.23%) and beta-linalool (35.01%) were main compounds in lavender oil.
      C. nepeta essential oil was characterized by a high percentage of piperitone
      oxide (59.07%) and limonene (9.05%). Essential oils have been found to have
      antimicrobial activity against all tested microorganisms. Classification and
      comparison of essential oils on the basis of their chemical composition and
      antibacterial activity were made by utilization of appropriate chemometric
      methods. The chemical principal component analysis (PCA) and hierachical cluster
      analysis (HCA) separated essential oils into two groups and two sub-groups. Thyme
      essential oil forms separate chemical HCA group and exhibits highest
      antibacterial activity, similar to tetracycline. Essential oils of lavender and
      C. nepeta in the same chemical HCA group were classified in different groups,
      within antibacterial PCA and HCA analyses. Lavender oil exhibits higher
      antibacterial ability in comparison with C. nepeta essential oil, probably based
      on the concept of synergistic activity of essential oil components.

PMID- 22389176
TI  - Statistical tests of genetic association for case-control study designs.
AB  - The central theme in case-control genetic association studies is to efficiently
      identify genetic markers associated with trait status. Powerful statistical
      methods are critical to accomplishing this goal. A popular method is the omnibus
      Pearson's chi-square test applied to genotype counts. To achieve increased power,
      tests based on an assumed trait model have been proposed. However, they are not
      robust to model misspecification. Much research has been carried out on enhancing
      robustness of such model-based tests. An analysis framework that tests the
      equality of allele frequency while allowing for different deviation from Hardy
      Weinberg equilibrium (HWE) between cases and controls is proposed. The proposed
      method does not require specification of trait models nor HWE. It involves only 1
      degree of freedom. The likelihood ratio statistic, score statistic, and Wald
      statistic associated with this framework are introduced. Their performance is
      evaluated by extensive computer simulation in comparison with existing methods.

PMID- 22389177
TI  - A stepwise retro-imino-ene as a key step in the mechanism of allene formation via
      the Crabbe acetylene homologation.
AB  - The mechanism of the acetylene homologation procedure accidentally discovered and
      further developed by Crabbe and coworkers is unknown. Kinetic isotope effect
      (KIE) experiments, however, suggest that an intramolecular hydrogen shift is the
      key step of the transformation. In this work, we present a computational study of
      this mechanism. We found that the reaction proceeds via an unexpected stepwise
      retro-imino-ene rearrangement. This mechanism justifies the role of Cu(I) as a
      reaction catalyst and is also compatible with the KIE experiments reported.

PMID- 22389179
TI  - Advanced transgenic approaches to understand alcohol-related phenotypes in
      animals.
AB  - During the past two decades, the use of genetically manipulated animal models in
      alcohol research has greatly improved the understanding of the mechanisms
      underlying alcohol addiction. In this chapter, we present an overview of the
      progress made in this field by summarizing findings obtained from studies of mice
      harboring global and conditional mutations in genes that influence alcohol
      related phenotypes. The first part reviews behavioral paradigms for modeling the
      different phases of the alcohol addiction cycle and other alcohol-induced
      behavioral phenotypes in mice. The second part reviews the current data available
      using genetic models targeting the main neurotransmitter and neuropeptide systems
      involved in the reinforcement and stress pathways, focusing on the phenotypes
      modeling the alcohol addiction cycle. Finally, the third part will discuss the
      current findings and future directions, and proposes advanced transgenic mouse
      models for their potential use in alcohol research.

PMID- 22389180
TI  - New pharmacological treatment strategies for relapse prevention.
AB  - Here we discuss treatment strategies that are based on pharmacological
      interventions to reduce craving and relapse in alcohol-dependent patients. We
      will first provide a historical overview about relapse prevention strategies. We
      will then review the development of disulfiram, naltrexone, acamprosate, and
      nalmefene and discuss their neurobiological modes of action. Then the concept of
      convergent genomic analysis will be introduced for the discovery of new molecular
      treatment targets. Finally, we will provide convincing evidence for the use of N
      methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs.
      Important conclusions of this review are: (i) learning from other addictive
      substances is very helpful-e.g., substitution therapies as applied to opiate
      addiction for decades could also be translated to alcoholics, (ii) the glutamate
      theory of alcohol addiction provides a convincing framework for the use of NMDA
      receptor antagonists as substitution drugs for alcohol-dependent patients, (iii)
      a combination of behavioral and pharmacological therapies may be the optimal
      approach for future treatment strategies-one promising example concerns the
      pharmacological disruption of reconsolidation processes of alcohol cue memories,
      (iv) given that many neurotransmitter systems are affected by chronic alcohol
      consumption, numerous druggable targets have been identified; consequently, a
      "cocktail" of different compounds will further improve the treatment situation,
      (v) in silico psychopharmacology, such as drug repurposing will yield new
      medications, and finally, (vi) the whole organism has to be taken into
      consideration to provide the best therapy for our patients. In summary, there is
      no other field in psychiatric research that has, in recent years, yielded so many
      novel, druggable targets and innovative treatment strategies than for alcohol
      addiction. However, it will still be several years before the majority of the
      "treatment-seeking population" will benefit from those developments.

PMID- 22389178
TI  - Modeling relapse in animals.
AB  - Alcohol addiction is a chronically relapsing disorder characterized by compulsive
      alcohol seeking and use. Alcohol craving and long-lasting vulnerability to
      relapse present a great challenge for the successful treatment of alcohol
      addiction. Therefore, relapse prevention has emerged as a critically important
      area of research, with the need for effective and valid animal models of relapse.
      This chapter provides an overview of the repertoire of animal models of craving
      and relapse presently available and employed in alcoholism research. These models
      include conditioned reinstatement, stress-induced reinstatement, ethanol priming
      induced reinstatement, conditioned place preference, Pavlovian spontaneous
      recovery, the alcohol deprivation effect, and seeking-taking chained schedules.
      Thus, a wide array of animal models is available that permit investigation of
      behaviors directed at obtaining access to alcohol, as well as neurobehavioral
      mechanisms and genetic factors that regulate these behaviors. These models also
      are instrumental for identifying pharmacological treatment targets and as tools
      for evaluating the efficacy of potential medications for the prevention of
      alcohol craving and relapse.

PMID- 22389182
TI  - Antioxidant and anti-alpha-glucosidase compounds from the rhizome of Peltiphyllum
      peltatum (Torr.) Engl.
AB  - The antioxidant, anti-alpha-glucosidase and anticholinesterase effects of the
      alcohol extract of fresh underground rhizomes of Peltiphyllum peltatum were
      studied. A potent antioxidant activity accompanied by a selective alpha
      glucosidase effect was observed for the crude extract. Further activity-guided
      fractionation (petroleum ether, chloroform, ethyl acetate, n-butanol and water)
      resulted in the identification of the ethyl acetate fraction with the highest
      antioxidant effect. Gallic acid, methyl-3-O-methyl gallate, catechin,
      gallocatechin, bergenin and 11-O-galloylbergenin were isolated from the ethyl
      acetate fraction. While all the isolated compounds did show a variable degree of
      radical scavenging effect, 11-O-galloylbergenin was identified as the selective
      alpha-glucosidase inhibitor. The isolation, structural elucidation and biological
      effects of these compounds are discussed.

PMID- 22389181
TI  - Fine particulate matter constituents and cardiopulmonary mortality in a heavily
      polluted Chinese city.
AB  - BACKGROUND: Although ambient fine particulate matter (PM(2.5); particulate matter
      <= 2.5 um in aerodynamic diameter) has been linked to adverse human health
      effects, the chemical constituents that cause harm are unknown. To our knowledge,
      the health effects of PM(2.5) constituents have not been reported for a
      developing country. OBJECTIVES: We examined the short-term association between
      PM(2.5) constituents and daily mortality in Xi'an, a heavily polluted Chinese
      city. METHODS: We obtained daily mortality data and daily concentrations of
      PM(2.5), organic carbon (OC), elemental carbon (EC), and 10 water-soluble ions
      for 1 January 2004 through 31 December 2008. We also measured concentrations of
      fifteen elements 1 January 2006 through 31 December 2008. We analyzed the data
      using overdispersed generalized linear Poisson models. RESULTS: During the study
      period, the mean daily average concentration of PM(2.5) in Xi'an was 182.2 ug/m3.
      Major contributors to PM(2.5) mass included OC, EC, sulfate, nitrate, and
      ammonium. After adjustment for PM(2.5) mass, we found significant positive
      associations of total, cardiovascular, or respiratory mortality with OC, EC,
      ammonium, nitrate, chlorine ion, chlorine, and nickel for at least one lag
      period. Nitrate demonstrated stronger associations with total and cardiovascular
      mortality than PM(2.5) mass. For a 1-day lag, interquartile range increases in
      PM(2.5) mass and nitrate (114.9 and 15.4 ug/m3, respectively) were associated
      with 1.8% [95% confidence interval (CI): 0.8%, 2.8%] and 3.8% (95% CI: 1.7%,
      5.9%) increases in total mortality. CONCLUSIONS: Our findings suggest that
      PM(2.5) constituents from the combustion of fossil fuel may have an appreciable
      influence on the health effects attributable to PM(2.5) in Xi'an.

PMID- 22389183
TI  - Interventional approaches to deep vein thrombosis.
AB  - The last decade has seen increased use of aggressive, catheter-based methods of
      treating deep vein thrombosis (DVT). In this article, we outline the risks,
      benefits, and uncertainties surrounding endovascular DVT therapies, describe
      clinical situations in which endovascular treatment options should reasonably be
      considered, and update the reader on new outcome data that pertains to catheter
      based DVT interventions. Endovascular thrombolytic therapy is reasonable to
      perform for selected patients with DVT causing acute limb-threatening circulatory
      compromise, acute inferior vena cava occlusion, or acute iliofemoral DVT for the
      purposes of limb salvage and relief of presenting DVT symptoms, and appears
      likely to prevent post-thrombotic syndrome (PTS) in patients with proximal DVT. A
      multicenter randomized trial, the ATTRACT Study, is currently underway in the
      United States to determine whether pharmacomechanical catheter-directed
      thrombolysis (PCDT) is sufficiently safe and effective to be recommended for
      routine use in proximal DVT patients. Selected patients with established moderate
      to-severe PTS in association with an occluded iliac vein or a refluxing saphenous
      vein may also be amenable to endovascular intervention to reduce venous
      hypertension, alleviate symptoms, and improve limb function and quality of life.
      Pending the results of further studies, an individualized approach to patient
      selection for interventional DVT therapies is recommended.

PMID- 22389184
TI  - Acculturation and depressive symptoms in Hispanic older adults: does perceived
      ethnic density moderate their relationship?
AB  - The negative impact of low acculturation on mental health in Hispanic older
      adults is widely known. The current study examined whether this association
      varied by a perceived density of people with same racial/ethnic backgrounds in
      neighborhoods. We hypothesized that the negative impact of low acculturation on
      mental health would be pronounced when they lived in neighborhoods with a low
      density of Hispanics. Using data from the Sacramento Area Latino Study on Aging
      (n = 1,267), hierarchical regression models of depressive symptoms were estimated
      with sets of predictors: (1) demographic variables, (2) acculturation, (3)
      perceived density of Hispanics in neighborhoods, and (4) an interaction between
      acculturation and perceived density of Hispanics. Supporting the hypothesis, the
      impact of acculturation on depressive symptoms was found to be moderated by the
      perceived density of Hispanics in neighborhoods. Findings suggest the importance
      of neighborhood characteristics in the lives of immigrant older adults.

PMID- 22389185
TI  - The incidence of depression by fertility status in overweight and obese Latina
      women.
AB  - The link between depression, obesity, and fertility status is poorly understood
      among Latina women. The Patient Health Questionnaire 9 (PHQ-9) is routinely
      administered in the Diabetes and Obesity in Reproductive Age women Clinic. We
      describe median PHQ-9 score and PHQ-9 score >=10 [indicative of Major Depressive
      Disorder (MDD)] by fertility status. Of the 76 eligible new patients seen between
      June 2008 and 2009, 18.4% (n = 14) had PHQ-9 scores indicative of MDD. Infertile
      women had marginally significantly higher PHQ-9 scores than non-infertile women
      (p = 0.08). 26.5% of infertile women and 12.2% of non-infertile women had a PHQ-9
      score indicative of MDD (p = 0.14). Number of previous births was inversely
      correlated with PHQ-9 score (R = -0.34, p = 0.002), those with no previous births
      had higher PHQ-9 scores (p = 0.001) and were more likely to have a PHQ-9 score
      indicative of MDD than those with previous births (28.6 vs. 9.8%, p = 0.04).
      Among non-infertile women, postpartum women had significantly lower PHQ-9 scores
      than non-postpartum women (p = 0.002). 4.6% of postpartum women and 21.1% of non
      postpartum women had a PHQ-9 indicative of MDD (p = 0.19). Further investigation
      is needed to determine if reproductive success is protective against MDD among
      overweight and obese urban Latinas. Overall, depression is common among
      overweight and obese reproductive-age Latinas and thus routine screening is
      recommended.

PMID- 22389186
TI  - Perceived discrimination and smoking among rural-to-urban migrant women in China.
AB  - Smoking may be a coping mechanism for psychosocial stress caused by
      discrimination. We conducted a cross-sectional survey of rural-to-urban migrant
      women working as restaurant/hotel workers (RHWs) and those working as sex workers
      (FSWs) in 10 Chinese cities to investigate whether perceived discrimination is
      associated with smoking. We interviewed RHWs at medical examination clinics and
      FSWs at entertainment venues. Modified Poisson regression was used to estimate
      prevalence ratios. Of the 1,696 RHWs and 532 FSWs enrolled, 155 (9.1%) and 63
      (11.8%) reported perceived discrimination, respectively. Perceived discrimination
      was independently associated with ever tried smoking (prevalence ratio [PR],
      1.71; 95% confidence interval [CI], 1.31-2.23) and current smoking (PR, 2.52; 95%
      CI, 1.32-4.79) among RHWs and ever tried smoking (PR, 1.36; 95% CI, 1.16-1.61)
      and current smoking (PR, 1.63; 95% CI, 1.28-2.06) among FSWs. Perceived
      discrimination is associated with higher prevalence of smoking among rural-to
      urban migrant women in China.

PMID- 22389187
TI  - Access to chiral alpha-bromo and alpha-H-substituted tertiary allylic alcohols
      via copper(I) catalyzed 1,2-addition of Grignard reagents to enones.
AB  - The catalytic asymmetric synthesis of tertiary alcohols by the addition of
      organometallic reagents to ketones is of central importance in organic chemistry.
      The resulting quaternary stereocentres are difficult to prepare selectively by
      other means despite their widespread occurrence in natural products and
      pharmaceuticals. Here we report on a new methodology which allows access to both
      alpha-bromo-substituted and alpha-H-substituted allylic tertiary alcohols with
      excellent yields, and enantioselectivities of up to 98% using the copper(I)
      catalysed 1,2-addition of Grignard reagents to enones. As an example, the
      methodology is applied in the synthesis of a chiral dihydrofuran.

PMID- 22389188
TI  - Ultrasensitive electrochemical detection of prostate-specific antigen (PSA) using
      gold-coated magnetic nanoparticles as 'dispersible electrodes'.
AB  - Herein, we demonstrate the use of modified gold-coated magnetic nanoparticles as
      'dispersible electrodes' which act as selective capture vehicles for
      electrochemical detection of prostate-specific antigen (PSA). A key advantage of
      this system is the ability to quantify non-electrochemical active analytes such
      as proteins with unprecedented detection limits and fast response times.

PMID- 22389189
TI  - Barriers to the detection and management of depression by palliative care
      professional carers among their patients: perspectives from professional carers
      and patients' family members.
AB  - INTRODUCTION: Clinical depression is highly prevalent yet underdetected and
      poorly managed within palliative care settings. OBJECTIVES: This qualitative
      study explored the identification, monitoring, and management of symptoms of
      depression in patients receiving palliative care from 2 juxtaposed perspectives
      that are of care providers and care recipients' family members. Examining the
      barriers that restrict professional carers detecting and managing depression in
      their patients was a central focus of the study. METHODS: Focus groups were held
      with 18 professional carers, including 8 holding managerial positions, across 2
      palliative care services, 1 regional and 1 metropolitan, which provided both
      inpatient and community-based care. Individual interviews were conducted with 10
      family members of patients who had received or were receiving palliative care
      through these services. RESULTS: Thematic analysis of these data identified that
      both professional carers and family members perceived that depression is a wide
      spread concern for patients receiving palliative care; however, numerous barriers
      were identified that affect professional carers' ability to identify depression.
      These included knowledge and training deficits, low self-efficacy, prioritization
      of physical concerns and time constraints, patient/family characteristics, and
      system/process issues. These themes (and related subthemes) are discussed in this
      article. CONCLUSIONS: Specialized training in depression is recommended for
      professional carers in order to improve their depression-related knowledge,
      detection skills, and self-efficacy. The ultimate goal of such training is to
      increase the rate of recognition of depression that in turn will lead to
      appropriate treatment for depressed patients.

PMID- 22389190
TI  - Suicide by do-not-resuscitate order.
AB  - Historically, medicine has been warned, "first, do no harm." In contemporary
      practice, however, the emergency response has generally been to err on the side
      of action with resuscitation efforts. Typically, it is only later on when medical
      therapy is considered futile that treatment is withdrawn. In such circumstances,
      a do-not-resuscitate (DNR) order is typically enacted as a part of an advance
      directive. However, when such patients attempt suicide, the approach to their
      care becomes complicated. Is the DNR order valid in a suicidal patient? What is
      the role of patient autonomy? How should an ethics consultant advise? This case
      details the method by which such issues should be approached in the emergent care
      of patients who have DNR order and attempt suicide.

PMID- 22389191
TI  - Modeling listeners' emotional response to music.
AB  - An overview of the computational prediction of emotional responses to music is
      presented. Communication of emotions by music has received a great deal of
      attention during the last years and a large number of empirical studies have
      described the role of individual features (tempo, mode, articulation, timbre) in
      predicting the emotions suggested or invoked by the music. However, unlike the
      present work, relatively few studies have attempted to model continua of
      expressed emotions using a variety of musical features from audio-based
      representations in a correlation design. The construction of the computational
      model is divided into four separate phases, with a different focus for
      evaluation. These phases include the theoretical selection of relevant features,
      empirical assessment of feature validity, actual feature selection, and overall
      evaluation of the model. Existing research on music and emotions and extraction
      of musical features is reviewed in terms of these criteria. Examples drawn from
      recent studies of emotions within the context of film soundtracks are used to
      demonstrate each phase in the construction of the model. These models are able to
      explain the dominant part of the listeners' self-reports of the emotions
      expressed by music and the models show potential to generalize over different
      genres within Western music. Possible applications of the computational models of
      emotions are discussed.

PMID- 22389192
TI  - Surface-modifiable free-floating films formed by multiway connection of collagen
      like triple-helical peptides.
AB  - Square-millimeter-sized free-floating translucent films are formed in
      physiological buffer by multiway connections between biotinylated collagen-like
      triple-helical peptides and avidin. Although the compositions of the films are
      almost constant, regardless of the ratios of the components loaded, their
      thicknesses can be controlled by the concentrations of the components. The film
      surfaces can be further modified by taking advantage of exposed biotin (or
      avidin) functionalities. The self-assembled films could serve as novel materials
      in biomedical and biosensing applications.

PMID- 22389193
TI  - The effect of tissue-engineered cartilage biomechanical and biochemical
      properties on its post-implantation mechanical behavior.
AB  - The insufficient load-bearing capacity of today's tissue-engineered (TE)
      cartilage limits its clinical application. Focus has been on engineering
      cartilage with enhanced mechanical stiffness by reproducing native biochemical
      compositions. More recently, depth dependency of the biochemical content and the
      collagen network architecture has gained interest. However, it is unknown whether
      the mechanical performance of TE cartilage would benefit more from higher content
      of biochemical compositions or from achieving an appropriate collagen
      organization. Furthermore, the relative synthesis rate of collagen and
      proteoglycans during the TE process may affect implant performance. Such insights
      would assist tissue engineers to focus on those aspects that are most important.
      The aim of the present study is therefore to elucidate the relative importance of
      implant ground substance stiffness, collagen content, and collagen architecture
      of the implant, as well as the synthesis rate of the biochemical constituents for
      the post-implantation mechanical behavior of the implant. We approach this by
      computing the post-implantation mechanical conditions using a composition-based
      fibril-reinforced poro-viscoelastic swelling model of the medial tibia plateau.
      Results show that adverse implant composition and ultrastructure may lead to post
      implantation excessive mechanical loads, with collagen orientation being the most
      critical variable. In addition, we predict that a faster synthesis rate of
      proteoglycans compared to that of collagen during TE culture may result in
      excessive loads on collagen fibers post-implantation. This indicates that even
      with similar final contents, constructs may behave differently depending on their
      development. Considering these aspects may help to engineer TE cartilage implants
      with improved survival rates.

PMID- 22389194
TI  - Nomifensine alters sex differences in striatal dopaminergic function.
AB  - A series of three experiments are presented in which the acute effects of the
      catecholamine reuptake inhibitor, nomifensine, upon striatal dopaminergic
      function are compared in female and male mice. In Experiment 1, treatment with
      nomifensine (5 mg kg-1), at 30 min prior to injection of methamphetamine (40 mg
      kg-1) significantly decreased the amount of striatal dopamine depletion in male,
      but not female, mice, thereby abolishing the sex difference in methamphetamine
      induced neurotoxicity (males > females). In Experiment 2, the methamphetamine
      evoked sex differences in dopamine and DOPAC output from superfused striatal
      tissue (males > females) were abolished in mice treated with nomifensine at 30
      min prior to tissue removal. In Experiment 3, the potassium chloride-evoked sex
      differences in dopamine and DOPAC output from superfused striatal tissue (females
      > males) were reversed in mice treated with nomifensine at 30 min prior to tissue
      removal. Taken together these results demonstrate the critical role played by
      catecholamine transporters in sex differences of dopaminergic function and
      suggest that this may involve the dopamine transporter, due to its high
      concentrations within the striatum. Such findings highlight the need for gender
      specific considerations in use of treatments that target reuptake transporters
      function.

PMID- 22389195
TI  - Enantioselective oxidative cross-dehydrogenative coupling of tertiary amines to
      aldehydes.

PMID- 22389196
TI  - Low-frequency electromagnetic fields do not alter responses of inflammatory genes
      and proteins in human monocytes and immune cell lines.
AB  - The effects of low frequency electromagnetic fields (LF EMF) on human health are
      the subject of on-going research and serious public concern. These fields
      potentially elicit small effects that have been proposed to have consequences,
      either positive or negative, for biological systems. To reveal potentially weak
      but biologically relevant effects, we chose to extensively examine exposure of
      immune cells to two different signals, namely a complex multiple waveform field,
      and a 50 Hz sine wave. These immune cells are highly responsive and, in vivo,
      modulation of cytokine expression responses can result in systemic health
      effects. Using time course experiments, we determined kinetics of cytokine and
      other inflammation-related genes in a human monocytic leukemia cell line, THP-1,
      and primary monocytes and macrophages. Moreover, cytokine protein levels in THP-1
      monocytes were determined. Exposure to either of the two signals did not result
      in a significant effect on gene and protein expression in the studied immune
      cells. Also, additional experiments using non-immune cells showed no effects of
      the signals on cytokine gene expression. We therefore conclude that these LF EMF
      exposure conditions are not expected to significantly modulate innate immune
      signaling.

PMID- 22389197
TI  - HIV vaccines: an attainable goal?
AB  - Publication of the first efficacious large-scale HIV vaccine trial in 2009
      prompted fresh hope that design of a protective vaccine against HIV may be
      achievable. In this review we explore the difficult task of eliciting protective
      immune responses to HIV and highlight the hurdles that vaccine design must still
      overcome.

PMID- 22389198
TI  - Extract of fermented brown rice induces apoptosis of human colorectal tumor cells
      by activating mitochondrial pathway.
AB  - Brown rice fermented with Aspergillus oryzae, designated as FBRA, is a dietary
      fiber-rich food, and fully appreciated as one of the prebiotics, which are
      generally considered to be beneficial to the health of the body, because of
      stimulating the growth and/or the activity of bacteria in the digestive system.
      To assess the effectiveness of FBRA as a functional food, the direct effect of
      FBRA extract on human colorectal tumor cells was examined. The exposure of HCT116
      cells to FBRA extract reduced their viabilities in a concentration-dependent
      manner, and the reduction of the cell viability might be attributed to the
      induction of apoptosis probably through the oxidative damage to the cells.
      Further studies showed that FBRA extract caused a significant elevation of Bax
      protein and a slight reduction of Bcl2 protein levels, and furthermore caused the
      activation of caspase-3 in the cells. Thus, it seems reasonable to conclude that
      FBRA extract can exert oxidative damage to the cells, resulting in apoptotic cell
      death by activating the mitochondrial pathway in human colorectal tumor cells.
      Therefore, daily intake of FBRA can be expected to be beneficial for preventing
      carcinogenesis and/or suppressing tumor growth in the digestive tract.

PMID- 22389199
TI  - Toxicity of voriconazole on corneal endothelial cells in an animal model.
AB  - AIMS: To determine the effect of intracamerally injected voriconazole on corneal
      endothelial cells in rabbit eyes. METHODS: Various concentrations of voriconazole
      (0%, 0.03%, 0.1%, 0.25%, 0.5% and 1%) were injected intracamerally in 36 eyes of
      18 rabbits (six eyes for each concentration). Measurements of endothelial cell
      counts and central corneal thickness were performed at 30, 60, 90 and 120 min
      after the injection. In each group, five of six corneas were used for the
      live/dead cell assay; staining with alizarin red and trypan was done. In one
      cornea from each group, scanning electron microscopy was performed. RESULTS:
      There was no significant difference in endothelial cell counts and central
      corneal thickness among the six groups at any time points. The live/dead cell
      assay revealed no difference in the mean percentage of dead endothelial cells
      among the six groups (p=0.504). However, scanning electron microscopy revealed
      blurring of cell border at voriconazole concentrations >= 0.25%, indicating cell
      wall damage. CONCLUSION: Intracameral injection of voriconazole did not induce a
      significant gross change in rabbit corneal endothelial cells up to a
      concentration of 1%. However, risk of microstructural damages might exist with a
      concentration of >= 0.25%.

PMID- 22389200
TI  - The hope and reality of long-acting hemophilia products.
AB  - Recombinant DNA technology and protein engineering are creating hope that we can
      address ongoing challenges in hemophilia care such as reducing the costs of
      therapy, increasing the availability to the developing world, and improving the
      functional properties of these proteins. Technological advances to improve the
      half-life of recombinant clotting factors have brought long-acting clotting
      factors for hemophilia replacement therapy closer to reality. Preclinical and
      clinical trial results are reviewed as well as the potential benefits and risks
      of these novel therapies.

PMID- 22389201
TI  - The body in the mind: on the relationship between interoception and embodiment.
AB  - The processing, representation, and perception of bodily signals (interoception)
      plays an important role for human behavior. Theories of embodied cognition hold
      that higher cognitive processes operate on perceptual symbols and that concept
      use involves reactivations of the sensory-motor states that occur during
      experience with the world. Similarly, activation of interoceptive representations
      and meta-representations of bodily signals supporting interoceptive awareness are
      profoundly associated with emotional experience and cognitive functions. This
      article gives an overview over present findings and models on interoception and
      mechanisms of embodiment and highlights its relevance for disorders that are
      suggested to represent a translation deficit of bodily states into subjective
      feelings and self-awareness.

PMID- 22389202
TI  - Is pesticide use related to Parkinson disease? Some clues to heterogeneity in
      study results.
AB  - BACKGROUND: Previous systematic reviews have indicated that pesticide exposure is
      possibly associated with Parkinson disease (PD). However, considerable
      heterogeneity has been observed in study results. OBJECTIVE: We aimed at
      providing an update of the literature published on PD and exposure to pesticides
      by performing a systematic review and meta-analysis. In addition, we investigated
      whether methodological differences between studies could explain the
      heterogeneity in study results. METHODS: We identified studies through a
      systematic literature search. We calculated summary risk ratios (sRRs) for
      pesticide exposure and subcategories using random effects meta-analyses and
      investigated sources of heterogeneity by meta-regression and stratified analyses.
      RESULTS: Thirty-nine case-control studies, four cohort studies, and three cross
      sectional studies were identified. An sRR of 1.62 [95% confidence interval (CI):
      1.40, 1.88] for pesticide exposure (ever vs. never) was found. Summary estimates
      for subclasses of pesticides indicated a positive association with herbicides and
      insecticides, but not with fungicides. Heterogeneity in individual study results
      was not related to study design, source of control population, adjustment of
      results for potential confounders, or geographical area. However, results were
      suggestive for heterogeneity related to differences in the exposure assessment.
      Job title-based exposure assignment resulted in a higher sRR (2.5; 95% CI: 1.5,
      4.1) than did assignment based on self-reported exposure (e.g., for self-reported
      ever/never exposure, sRR = 1.5; 95% CI: 1.3, 1.8). CONCLUSIONS: This review
      affirms the evidence that exposure to herbicides and insecticides increase the
      risk of PD. Future studies should focus on more objective and improved methods of
      pesticide exposure assessment.

PMID- 22389204
TI  - MHC class II tetramers.
AB  - MHC class II tetramers have emerged as an important tool for characterization of
      the specificity and phenotype of CD4 T cell immune responses, useful in a large
      variety of disease and vaccine studies. Issues of specific T cell frequency,
      biodistribution, and avidity, coupled with the large genetic diversity of
      potential class II restriction elements, require targeted experimental design.
      Translational opportunities for immune disease monitoring are driving the rapid
      development of HLA class II tetramer use in clinical applications, together with
      innovations in tetramer production and epitope discovery.

PMID- 22389205
TI  - Recovery of functionally active recombinant human phospholipid scramblase 1 from
      inclusion bodies using N-lauroyl sarcosine.
AB  - Human phospholipid scramblase (hPLSCR1) is a transmembrane protein involved in
      rapid bidirectional scrambling of phospholipids across the plasma membrane in
      response to elevated intracellular calcium (Ca(2+)) levels. Overexpression of
      recombinant hPLSCR1 in Escherichia coli BL21 (DE3) leads to its deposition in
      inclusion bodies (IBs). N-lauroyl sarcosine was used to solubilize IBs and to
      recover functionally active hPLSCR1 from them. Protein was purified to
      homogeneity by nickel-nitrilotriacetic acid (Ni(2+)-NTA) affinity chromatography
      and was >98% pure. Functional activity of the purified protein was validated by
      in vitro reconstitution studies, ~18% of 7-nitrobenz-2-oxa-1, 3-diazol-4-yl
      phosphatidylcholine (NBD-PC) phospholipids was translocated across the lipid
      bilayer in the presence of Ca(2+) ions. Far ultraviolet circular dichroism (UV
      CD) studies reveal that the secondary structure of protein is predominantly an
      alpha-helix, and under nondenaturing conditions, the protein exists as a monomer.
      Here we describe a method to purify recombinant membrane protein with higher
      yield than previously described methods involving renaturation techniques.

PMID- 22389206
TI  - Analyzing the dynamics of cell growth and protein production in mammalian cell
      fed-batch systems using logistic equations.
AB  - The logistic modeling approach was used to describe experimental viable cell
      density (X) and product concentration (P) data from two industrial fed-batch
      mammalian cell culture processes with maximum product concentrations in the 3.0
      9.4 g/l range. In both cases, experimental data were well described by the
      logistic equations and the resulting specific growth rate and protein
      productivity profiles provided useful insights into the process kinetics.
      Subsequently, sensitivity equations for both the X and P models were analyzed
      which helped characterize the influence of model parameters on X and P time
      courses. This was augmented by conventional sensitivity analyses where five
      values of each model parameter, 25% apart, were used to generate X and P time
      courses. Finally, results from sensitivity analysis were used to simulate X and P
      time courses that were reflective of typical early- and late-stage fed-batch cell
      culture processes. Different combinations of the logistic model parameters were
      used to arrive at the same final product concentration demonstrating the ability
      of the logistic approach to describe the multitude of process paths that result
      in the same final product concentration. Overall, the capability of the logistic
      equations to well describe X and P data from fed-batch cultures, coupled with
      their ability to simulate the multitude of paths leading up to the desired cell
      density and product concentration profiles, make them a useful tool during
      mammalian cell fed-batch process development.

PMID- 22389207
TI  - Genotoxicity of pesticide mixtures present in the diet of the French population.
AB  - Consumers may be simultaneously exposed to several pesticide residues in their
      diet. A previous study identified the seven most common pesticide mixtures to
      which the French population was exposed through food consumption in 2006. The aim
      of this study was to investigate if the seven mixtures are potentially cytotoxic
      and genotoxic and if so, whether compounds in a same mixture have a combined
      effect. The cytotoxicity and genotoxicity of the seven mixtures were investigated
      with a new assay (gamma-H2AX) using four human cell lines (ACHN, SH-SY5Y, LS
      174T, and HepG2). Mixtures were tested at equimolar concentrations and also at
      concentrations reflecting their actual proportion in the diet. Irrespective of
      the cell line tested, parallel cytotoxicity of the seven mixtures was observed.
      Only one mixture was genotoxic for the HepG2 cells at concentrations = 3 MUM in
      equimolar proportion and at 30 MUM in actual proportion. Caspase 3/7 activity,
      the comet assay, and reactive oxygen species production were also investigated
      using the same mixture and HepG2 cells. Our results suggest that pesticide
      metabolites from the mixture generated by HepG2 cells were responsible for the
      observed damage to DNA. Among the five compounds in the genotoxic mixture, only
      fludioxonil and cyprodinil were genotoxic for HepG2 cells alone at concentrations
      = 4 and 20 MUM, respectively. Our data suggest a combined genotoxic effect of the
      mixture at low concentrations with a significantly higher effect of the mixture
      of pesticides than would be expected from the response to the individual
      compounds. Environ. Mol. Mutagen. 2012. (c) 2012 Wiley Periodicals, Inc.

PMID- 22389208
TI  - Playing God and the intrinsic value of life: moral problems for synthetic
      biology?
AB  - Most of the reports on synthetic biology include not only familiar topics like
      biosafety and biosecurity but also a chapter on 'ethical concerns'; a variety of
      diffuse topics that are interrelated in some way or another. This article deals
      with these 'ethical concerns'. In particular it addresses issues such as the
      intrinsic value of life and how to deal with 'artificial life', and the fear that
      synthetic biologists are tampering with nature or playing God. Its aim is to
      analyse what exactly is the nature of the concerns and what rationale may lie
      behind them. The analysis concludes that the above-mentioned worries do not give
      genuine cause for serious concern. In the best possible way they are interpreted
      as slippery slope arguments, yet arguments of this type need to be handled with
      care. It is argued that although we are urged to be especially vigilant we do not
      have sufficiently cogent reasons to assume that synthetic biology will cause such
      fundamental hazards as to warrant restricting or refraining from research in this
      field.

PMID- 22389209
TI  - Contentious problems in bioscience and biotechnology: a pilot study of an
      approach to ethics education.
AB  - This manuscript describes a pilot study in ethics education employing a problem
      based learning approach to the study of novel, complex, ethically fraught,
      unavoidably public, and unavoidably divisive policy problems, called "fractious
      problems," in bioscience and biotechnology. Diverse graduate and professional
      students from four US institutions and disciplines spanning science, engineering,
      humanities, social science, law, and medicine analyzed fractious problems
      employing "navigational skills" tailored to the distinctive features of these
      problems. The students presented their results to policymakers, stakeholders,
      experts, and members of the public. This approach may provide a model for
      educating future bioscientists and bioengineers so that they can meaningfully
      contribute to the social understanding and resolution of challenging policy
      problems generated by their work.

PMID- 22389210
TI  - Failure of engineering artifacts: a life cycle approach.
AB  - Failure is a central notion both in ethics of engineering and in engineering
      practice. Engineers devote considerable resources to assure their products will
      not fail and considerable progress has been made in the development of tools and
      methods for understanding and avoiding failure. Engineering ethics, on the other
      hand, is concerned with the moral and social aspects related to the causes and
      consequences of technological failures. But what is meant by failure, and what
      does it mean that a failure has occurred? The subject of this paper is how
      engineers use and define this notion. Although a traditional definition of
      failure can be identified that is shared by a large part of the engineering
      community, the literature shows that engineers are willing to consider as
      failures also events and circumstance that are at odds with this traditional
      definition. These cases violate one or more of three assumptions made by the
      traditional approach to failure. An alternative approach, inspired by the notion
      of product life cycle, is proposed which dispenses with these assumptions.
      Besides being able to address the traditional cases of failure, it can deal
      successfully with the problematic cases. The adoption of a life cycle perspective
      allows the introduction of a clearer notion of failure and allows a
      classification of failure phenomena that takes into account the roles of
      stakeholders involved in the various stages of a product life cycle. 

PMID- 22389211
TI  - Concave versus planar geometries for the hierarchical organization of mesoscopic
      3D helical fibers.
AB  - Chromophore-peptide systems: a study on a series of pentapeptides covalently
      connected to planar pi systems (1 a and 1 b) or to a curved pi system (1 c)
      showed the influence of the concave shape on the efficient chiral transmission at
      nano- and mesoscales. Control over the hierarchical growth by H bonding, pi-pi,
      and solvophobic interactions made possible the efficient generation of
      electroactive 3D helical fibers.

PMID- 22389212
TI  - Associated vascular lesions in patients with spontaneous coronary artery
      dissection.
AB  - AIM: To identify vascular abnormalities in patients presenting with spontaneous
      coronary artery dissection (SCAD). METHODS: We performed a whole-body MR
      angiography and a duplex sonography of the renal and carotid arteries in 12
      patients (9 women, 3 men) with SCAD to identify vascular abnormalities. RESULTS:
      MR angiography revealed abnormalities of the renal arteries in 3/12 patients
      (25%). All 3 patients were women, 2 presented with changes suggesting
      fibromuscular dysplasia (FMD), 1 had a spontaneous renal artery dissection. No
      other vascular abnormalities were identified in any of the patients. Duplex
      sonography confirmed MR findings and showed non-significant renal artery stenoses
      in both patients with FMD. CONCLUSIONS: Abnormalities of the renal arteries were
      found in 3/12 (25%) of the patients with SCAD. No other vascular abnormalities
      were identified. Additional diagnostic tests of the renal arteries such as renal
      artery angiography or duplex sonography may be considered in patients presenting
      with SCAD.

PMID- 22389213
TI  - 6-Gingerol induces apoptosis through lysosomal-mitochondrial axis in human
      hepatoma G2 cells.
AB  - 6-Gingerol, a major phenolic compound derived from ginger, has been known to
      possess anticarcinogenic activities. However, the mechanisms are not well
      understood. In our previous study, it was demonstrated that lysosome and
      mitochondria may be the primary targets for 6-gingerol in HepG2 cells. Therefore,
      the aim was to evaluate lysosome-mitochondria cross-signaling in 6-gingerol
      induced apoptosis. Apoptosis was detected by Hoechst 33342 and TUNEL assay after
      24 h treatment, and the destabilization of lysosome and mitochondria were early
      upstream initiating events. This study showed that cathepsin D played a crucial
      role in the process of apoptosis. The release of cathepsin D to the cytosol
      appeared to be an early event that preceded the release of cytochrome c from
      mitochondria. Moreover, inhibition of cathepsin D activity resulted in suppressed
      release of cytochrome c. To further determine the involvement of oxidative stress
      in 6-gingerol-induced apoptosis, the intracellular generation of reactive oxygen
      species (ROS) and reduced glutathione (GSH) were examined. Taken together, these
      results suggest that cathepsin D may be a positive mediator of 6-gingerol induced
      apoptosis in HepG2 cells, acting upstream of cytochrome c release, and the
      apoptosis may be associated with oxidative stress.

PMID- 22389214
TI  - Cloning the uteroglobin gene promoter from the relic volcano rabbit (Romerolagus
      diazi) reveals an ancient estrogen-response element.
AB  - To gain further insight on the estrogen-dependent transcriptional regulation of
      the uteroglobin (UG) gene, we cloned the 5'-flanking region of the UG gene from
      the phylogenetically ancient volcano rabbit (Romerolagus diazi; Rd). The cloned
      region spans 812 base pairs (bp; -812/-1) and contains a noncanonical TATA box
      (TACA). The translation start site is 48 bp downstream from the putative
      transcription initiation site (AGA), and is preceded by a consensus Kozak box.
      Comparison of the Rd-UG gene with that previously isolated from rabbits
      (Oryctolagus cuniculus) showed 93% in sequence identity as well as a number of
      conserved cis-acting elements, including the estrogen-response element (ERE; 
      265/-251), which differs from the consensus by two nucleotides. In MCF-7 cells,
      17beta-estradiol (E(2)) induced transcription of a luciferase reporter driven by
      the Rd-UG promoter in a similar manner as in an equivalent rabbit UG reporter;
      the Rd-UG promoter was 30% more responsive to E(2) than the rabbit promoter.
      Mutagenesis studies on the Rd-ERE confirmed this cis-element as a target of E(2)
      as two luciferase mutant reporters of the Rd-promoter, one with the rabbit and
      the other with the consensus ERE, were more responsive to the hormone than the
      wild-type reporter. Gel shift and super-shift assays showed that estrogen
      receptor-alpha indeed binds to the imperfect palindromic sequence of the Rd-ERE.

PMID- 22389215
TI  - The miR-17/92 cluster is targeted by STAT5 but dispensable for mammary
      development.
AB  - Genome wide analysis revealed the miR-17/92 cluster as a STAT5 target. This
      cluster encodes six microRNAs, which predictably target genes that play a role in
      mammary gland development. In this study, we have deleted the miR-17/92 cluster
      in mammary stem cells and evaluated in the mouse its function during mammary
      gland development. Loss of the miR-17/92 cluster did not affect mammary
      development from prepuberty to lactation. Our studies demonstrated that, while
      expression of the miR-17/92 cluster is under control of the key mammary
      transcription factor STAT5, its presence is not required for normal mammary
      development or lactation.

PMID- 22389217
TI  - Plagiarism, duplicate publication, and reviews.

PMID- 22389216
TI  - Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement
      after lenalidomide therapy.
AB  - POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and
      skin changes) syndrome is a rare multisystemic disease associated with plasma
      cell dyscrasia and increased serum or plasma vascular endothelial growth factor
      (VEGF) levels, the latter likely responsible for several POEMS syndrome
      manifestations. Whereas peripheral neuropathy is the main neurological feature
      and a mandatory diagnostic criterium, central nervous system involvement is less
      common except for papilledema and stroke. We recently reported the frequent
      occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS
      syndrome patients. Meningeal histopathology revealed hyperplasia of
      meningothelial cells, neovascularization, and obstructive vessel remodeling
      without inflammatory signs pointing to a role of VEGF in the meningeal
      manifestations. Here, we report the dramatic pachymeningeal improvement in
      patients undergoing lenalidomide therapy. These findings support the therapeutic
      role of lenalidomide and might shed further light on the pathophysiology of the
      disease

PMID- 22389218
TI  - Manske's musings.

PMID- 22389219
TI  - Clinical images of the recurrent motor branch of the median nerve.

PMID- 22389220
TI  - Reducing personal exposure to particulate air pollution improves cardiovascular
      health in patients with coronary heart disease.
AB  - BACKGROUND: Air pollution exposure increases cardiovascular morbidity and
      mortality and is a major global public health concern. OBJECTIVES: We
      investigated the benefits of reducing personal exposure to urban air pollution in
      patients with coronary heart disease. METHODS: In an open randomized crossover
      trial, 98 patients with coronary heart disease walked on a predefined route in
      central Beijing, China, under different conditions: once while using a highly
      efficient face mask, and once while not using the mask. Symptoms, exercise,
      personal air pollution exposure, blood pressure, heart rate, and 12-lead
      electrocardiography were monitored throughout the 24-hr study period. RESULTS:
      Ambient air pollutants were dominated by fine and ultrafine particulate matter
      (PM) that was present at high levels [74 MUg/m3 for PM(2.5) (PM with aerodynamic
      diamater <2.5 um)]. Consistent with traffic-derived sources, this PM contained
      organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing,
      generating large amounts of free radicals. The face mask was well tolerated, and
      its use was associated with decreased self-reported symptoms and reduced maximal
      ST segment depression (-142 vs. -156 MUV, p = 0.046) over the 24-hr period. When
      the face mask was used during the prescribed walk, mean arterial pressure was
      lower (93 +/- 10 vs. 96 +/- 10 mmHg, p = 0.025) and heart rate variability
      increased (high-frequency power: 54 vs. 40 msec2, p = 0.005; high-frequency
      normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive
      differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to
      influence heart rate or energy expenditure. CONCLUSIONS: Reducing personal
      exposure to air pollution using a highly efficient face mask appeared to reduce
      symptoms and improve a range of cardiovascular health measures in patients with
      coronary heart disease. Such interventions to reduce personal exposure to PM air
      pollution have the potential to reduce the incidence of cardiovascular events in
      this highly susceptible population.

PMID- 22389221
TI  - Early neutralizing IgG response to Chikungunya virus in infected patients targets
      a dominant linear epitope on the E2 glycoprotein.
AB  - Chikungunya virus (CHIKV) and related arboviruses have been responsible for large
      epidemic outbreaks with serious economic and social impact. The immune
      mechanisms, which control viral multiplication and dissemination, are not yet
      known. Here, we studied the antibody response against the CHIKV surface antigens
      in infected patients. With plasma samples obtained during the early convalescent
      phase, we showed that the naturally-acquired IgG response is dominated by IgG3
      antibodies specific mostly for a single linear epitope 'E2EP3'. E2EP3 is located
      at the N-terminus of the E2 glycoprotein and prominently exposed on the viral
      envelope. E2EP3-specific antibodies are neutralizing and their removal from the
      plasma reduced the CHIKV-specific antibody titer by up to 80%. Screening of E2EP3
      across different patient cohorts and in non-human primates demonstrated the value
      of this epitope as a good serology detection marker for CHIKV infection already
      at an early stage. Mice vaccinated by E2EP3 peptides were protected against CHIKV
      with reduced viremia and joint inflammation, providing a pre-clinical basis for
      the design of effective vaccine against arthralgia-inducing CHIKV and other
      alphaviruses.

PMID- 22389222
TI  - Astrocyte calcium signaling and epilepsy.
AB  - Studies performed over the last decade, in both animal models and human epilepsy,
      support the view that a defective K(+) buffering due to an altered expression of
      K(+) and aquaporin channels in astrocytes represents a possible causative factor
      of the pathological neuronal hyperexcitability in the epileptic brain. More
      recent studies, however, reappraised the role of neurons in epileptogenesis and
      suggested that Ca(2+)-dependent gliotransmission directly contributes to the
      excessive neuronal synchronization that predisposes the brain network to
      seizures. Significant support for this view comes from the finding that
      astrocytes from hyperexcitable networks respond to neuronal signals with massive
      Ca(2+) elevations and generate a recurrent excitatory loop with neurons that has
      the potential to promote a focal seizure. The specific aim of this review is on
      the one hand, to provide an overview of the experimental findings that hinted at
      a direct role of Ca(2+)-dependent gliotransmission in the generation of seizure
      like discharges in models of focal epilepsy; and on the other hand, to emphasize
      the importance of developing new experimental tools that could help us to
      understand the amazing complexity of neuron-astrocyte partnership in brain
      disorders.

PMID- 22389224
TI  - Surgical technique arthroscopic posterior glenoidplasty for posterosuperior
      glenoid impingement in throwing athletes.
AB  - BACKGROUND: Posterosuperior glenoid impingement (PSGI) is the repetitive
      impaction of the supraspinatus tendon insertion on the posterosuperior glenoid
      rim in abduction and external rotation. While we presume the pain is mainly
      caused by mechanical impingement, this explanation is controversial. If
      nonoperative treatment fails, arthroscopic debridement of tendinous and labral
      lesions has been proposed but reportedly does not allow a high rate of return to
      sports. In 1996, we proposed adding abrasion of the bony posterior rim, or
      glenoidplasty. DESCRIPTION OF TECHNIQUE: After arthroscopic assessment of
      internal impingement in abduction-extension-external rotation, extensive
      posterior labral and partial tendinous tear debridement is performed.
      Glenoidplasty involves recognition of a posterior glenoid spur and when present
      subsequent abrasion with a motorized burr. METHODS: We retrospectively reviewed
      27 throwing athletes treated between 1996 and 2008. Age averaged 27 years. CT
      arthrogram showed bony changes on the posterior glenoid rim in 21 shoulders. We
      evaluated 26 of the 27 patients at a minimum followup of 19 months (mean, 47
      months; range, 19-123 months). RESULTS: Eighteen of the 26 patients resumed their
      former sport level. Six improved but had to change to an inferior sport level or
      another sport. Two patients did not improve after the procedure, one of whom
      changed sport practice. There were no complications or posterior instability. In
      the 15 patients who had radiographs at followup times from 20 to 87 months, we
      observed no arthritis or osteophyte. CONCLUSIONS: Comparison with an earlier
      series of soft tissue debridement shows glenoidplasty improves the likelihood of
      resuming a former sport level in patients with PSGI. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22389225
TI  - Bio-inspired phosphole-lipids: from highly fluorescent organogels to mechanically
      responsive FRET.
AB  - Sensitive gels: the amphiphilic features of phosphole-lipids lead to intriguing
      self-assembly properties and the formation of highly fluorescent organogels.
      Moreover, the dynamic structural features of the system make it possible to
      amplify the mechanochromic emission shifts (100 nm) in a donor-acceptor system
      through thermally and mechanically responsive fluorescence resonance energy
      transfer (FRET).

PMID- 22389226
TI  - Early appearance of neutralizing immunoglobulin G3 antibodies is associated with
      chikungunya virus clearance and long-term clinical protection.
AB  - BACKGROUND: Chikungunya virus (CHIKV) and related arboviruses have been
      responsible for large epidemic outbreaks with serious economic and social impact.
      Although infected individuals clear the virus from the blood, some develop
      debilitating and prolonged arthralgia. METHODS: We investigated specificity and
      strength of antibody responses in a longitudinal study on CHIKV-infected patients
      and analyzed their association with viral load, cytokine profile, and severity.
      RESULTS: We found that CHIKV-specific response is dominated by immunoglobulin G3
      (IgG3) antibodies. The antibodies were neutralizing, and patients with high
      viremia rapidly developed high levels of anti-CHIKV antibodies of this specific
      isotype. Although these patients endured a more severe disease progression during
      the acute viremic phase, they cleared the virus faster and did not experience
      persistent arthralgia. However, significant persistent arthralgia was observed in
      patients with low viremia who developed IgG3 at a later stage. CONCLUSIONS:
      Absence of early CHIKV-specific IgG3 may therefore serve as a specific marker of
      patients with increased risk of disease.

PMID- 22389227
TI  - In situ remediation of contaminated sediments using carbonaceous materials.
AB  - Carbonaceous materials (CM), such as activated carbons or biochars, have been
      shown to significantly reduce porewater concentrations and risks by binding
      hydrophobic organic compounds (HOCs) present in aquatic sediments. In the present
      study, the authors review the current state-of-the-art use of CM as an extensive
      method for sediment remediation, covering both technical and ecological angles.
      The review addresses how factors such as CM type, particle size and dosage,
      sediment characteristics, and properties of contaminants affect the effectiveness
      of CM amendment to immobilize HOCs in aquatic sediments. The authors also review
      the extent to which CM may reduce bioaccumulation and toxicity of HOCs and
      whether CM itself has negative effects on benthic species and communities. The
      review is based on literature and datasets from laboratory as well as field
      trials with CM amendments. The presence of phases such as natural black carbon,
      oil, or organic matter in the sediment reduces the effectiveness of CM
      amendments. Carbonaceous material additions appear to improve the habitat quality
      for benthic organisms by reducing bioavailable HOC concentrations and toxicity in
      sediment. The negative effects of CM itself on benthic species, if any, have been
      shown to be mild. The beneficial effects of reducing toxicity at low CM
      concentrations most probably outweigh the mild negative effects observed at
      higher CM concentrations.

PMID- 22389228
TI  - Schisandra chinensis prevents hepatic lipid peroxidation and oxidative stress in
      rats subjected to heat environmental stress.
AB  - Increases in temperature cause a proliferation of heat-stress-related disorders
      by disrupting the body's homeostasis system, particularly when excessive levels
      of reactive oxygen species disrupt the balance of antioxidant defence systems.
      Thus, controlling oxidative stress is important for the regulation of body
      homeostasis. Schisandra chinensis (SC) has a potential effect on antioxidants and
      is resistant to high temperatures. However, the mechanism of SC during heat
      stress is unclear. Therefore, we evaluated the effect of SC on heat stress by
      performing several bioactive genetic assays on Sprague Dawley (SD) rats. The
      results demonstrated that heat stress significantly increased in heat-stress
      related gene expression whereas it was dramatically reduced in the gene
      expression of the SC group. The genes related to oxidative stress were also
      significantly suppressed in the SC group compared with those of the heat stress
      group. Furthermore, there was a greater decrease in the MDA content of the SD
      rats in the orally administered SC group than in the heat exposure group. Thus,
      we demonstrate that SC has a protective effect on heat stress as a result of its
      strong antioxidant properties and the prevention of lipid peroxidation.

PMID- 22389229
TI  - Obesity and human biology: toward a global perspective.
AB  - Overweight bodies will soon be the modal human form. In this special issue of
      American Journal of Human Biology, authors use varied approaches to examine the
      expansion of obesity globally, particularly what shape variability in people's
      vulnerability to weight gain and its negative effects. The contributions together
      highlight how complex pathways between biology and health related to excess
      weight are strongly medicated, at multiple levels, by both socio-ecological
      context and life history. A systems approach, which can place human biological
      and biocultural variation iteratively within the broader contexts of developing
      and globalizing adiposity, will be a useful next step to informing effective
      prevention and intervention efforts.

PMID- 22389230
TI  - Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE)
      Guideline.
AB  - PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless
      ingestible capsule technique that allows exploration of the colon without the
      need for sedation and gas insufflation. Although it is already available in
      European and other countries, the clinical indications for CCE as well as the
      reporting and work-up of detected findings have not yet been standardized. The
      aim of this evidence-based and consensus-based guideline, commissioned by the
      European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare
      providers with a comprehensive framework for potential implementation of this
      technique in a clinical setting.

PMID- 22389231
TI  - Benchmarking patient experiences in colonoscopy using the Global Rating Scale.
AB  - INTRODUCTION: The Global Rating Scale (GRS) is a quality assurance program that
      was developed in England to assess patient-centered care in endoscopy. The aim of
      the current study was to evaluate patient experiences of colonoscopy using the
      GRS in order to compare different departments and to provide benchmarks. The
      study also evaluated factors associated with patient satisfaction. METHODS: A GRS
      questionnaire was used both before and after the procedure in outpatients
      undergoing colonoscopy. The questionnaire assessed the processes associated with
      the colonoscopy, from making the appointment up until discharge. Mean values and
      ranges of 12 endoscopy departments were calculated together with P values in
      order to assess heterogeneity. RESULTS: In total, 1904 pre-procedure and 1532 (80
      %) post-procedure questionnaires were returned from 12 endoscopy departments. The
      mean time patients had to wait for their procedure was 4.3 weeks (range 3.1 - 5.8
      weeks), and 54 % (range 35 - 64 %; P < 0.001) reported being given a choice of
      appointment dates/times. Discomfort during colonoscopy was reported by 20 %
      (range 8 - 40 %; P < 0.001). Recovery room privacy was satisfactory for 76 % of
      patients (range 66 - 90 %; P < 0.05). The majority of patients reported being
      sufficiently informed about what to do in case of problems after discharge (79 %,
      range 43 - 98 %; P < 0.001), and 85 % of individuals stated that they would be
      willing to repeat the colonoscopy procedure (range 72 - 92 %; P < 0.001). Factors
      associated with a decreased willingness to return were the burdensome bowel
      preparation (odds ratio [OR] = 0.25; P < 0.001), "rushing staff" attitude (OR =
      0.57; P < 0.05), low acceptance of the procedure (OR = 0.42; P < 0.01), and more
      discomfort than expected (OR = 0.54; P < 0.05). CONCLUSION: Overall patient
      experiences with colonoscopy were satisfactory, but they also showed considerable
      variation. This study shows that use of a GRS patient questionnaire is feasible
      in the Dutch endoscopy setting for the assessment of patient experience. The
      significant variability between endoscopy units can be used to benchmark services
      and enable shortcomings to be identified.

PMID- 22389232
TI  - Nonanesthesiologist-administered propofol sedation: from the exception to
      standard practice. Sedation and monitoring trends over 20 years.
AB  - The practice of sedation, including monitoring practice for digestive endoscopy,
      continues to evolve throughout the world. In many countries, including
      Switzerland, there is a trend towards increased utilization of sedation during
      both routine and advanced endoscopic procedures. Sedation improves patient
      satisfaction with endoscopy and also improves the quality of the examination. In
      addition, a trend can be observed towards an increasing use of propofol as the
      preferred sedative drug. Here we review the latest published data from surveys
      describing sedation and monitoring practice in different countries and compare
      them with our own data from successive nationwide surveys among Swiss
      gastroenterologists over a period of 20 years. This development between these
      socioeconomically very similar Western industrialized countries, however, shows
      some unique and surprising differences. In Germany and Switzerland, propofol use
      has become increasingly widespread, in Switzerland even to the extent that during
      the last few years propofol has overtaken benzodiazepine sedation, with an
      absolute majority of Swiss gastroenterologists using it without the assistance of
      an anesthesiologist. In addition, the change in Switzerland reflects a successful
      generalization of nonanesthesiologist-administered propofol (NAAP) sedation from
      the hospital setting to private practice.

PMID- 22389233
TI  - Endoscopic ultrasound-guided vascular therapy: is it safe and effective?
AB  - Recent developments in therapeutic endoscopic ultrasound (EUS) have enabled new
      approaches to the management of refractory gastrointestinal bleeding, including
      EUS-guided sclerotherapy and vessel embolization. Few cases have been reported in
      the literature. Eight patients were admitted for severe, refractory
      gastrointestinal bleeding, seven of whom were actively bleeding. Causes of
      bleeding were gastric varices secondary to portal hypertension (n = 3);
      gastroduodenal artery aneurysm or fundal aneurysmal arterial malformation (n =
      3); and Dieulafoy's ulcer (n = 2); the latter five patients having arterial
      bleeding. During the procedures, the bleeding vessel was punctured with a 19
      gauge needle then injected with a sclerosing agent (cyanoacrylate glue [n = 6] or
      polidocanol 2 % [n = 2]) under Doppler control. The median follow-up time was 9
      months (3 - 18 months). In all 10 endoscopic procedures were performed. The
      procedure was successful at the first attempt in seven out of eight patients
      (87.5 %). No clinical complications were observed, although in one case there was
      diffusion of cyanoacrylate in the hepatic artery. The seven successful cases all
      showed immediate and complete disappearance of the Doppler flow signal at the end
      of the procedure. This retrospective study highlights the utility of EUS-guided
      vascular therapy. However, more large randomized studies should be conducted to
      confirm these results.

PMID- 22389234
TI  - Yield and impact of emergency capsule enteroscopy in severe obscure-overt
      gastrointestinal bleeding.
AB  - BACKGROUND AND STUDY AIMS: Patients with obscure-overt gastrointestinal bleeding
      (OOGIB) are defined by overt hemorrhage and negative upper and lower endoscopy
      findings. At present, the place of emergency capsule enteroscopy in patients with
      severe OOGIB is unknown. The aim of this study was to assess the diagnostic yield
      and the impact of emergency capsule enteroscopy on further management in patients
      with severe OOGIB. PATIENTS AND METHODS: Between 2003 and 2010, we
      retrospectively included all patients with severe OOGIB who underwent emergency
      capsule enteroscopy in the 24-48 h following negative urgent upper and lower
      endoscopy. Severe OOGIB was defined by ongoing bleeding with hemodynamic
      instability and/or the need for significant red blood cell transfusion. RESULTS:
      Out of 5744 patients hospitalized in our Gastrointestinal Bleeding Unit, 55 (1%)
      presented with severe OOGIB and underwent emergency capsule enteroscopy. Capsule
      enteroscopy showed blood in 41 patients (75%) and lesions in 37 patients (67%).
      Findings included small bowel angiodysplasia in 19 patients (35%), ulcers in 7
      (13%), tumors in 5 (9%), small-bowel varices in 2 (3%), cecum angiodysplasia in 4
      (7%), fresh blood in small bowel without identified lesion in 12 (22%). Specific
      diagnostic and therapeutic procedures were undertaken in 78 % of patients.
      Further management included endoscopy (54%), surgery (22%), and radiology (2%).
      CONCLUSIONS: Emergency capsule enteroscopy identified bleeding lesions in 67 % of
      patients with severe OOGIB. Emergency capsule enteroscopy seems to be a promising
      diagnostic tool with a subsequent impact on clinical management in patients with
      severe OOGIB.

PMID- 22389236
TI  - Can we cure cholangiocarcinoma with neoadjuvant chemoradiation and liver
      transplantation? Time for a multicenter trial.

PMID- 22389235
TI  - Bulbispermine: a crinine-type Amaryllidaceae alkaloid exhibiting cytostatic
      activity toward apoptosis-resistant glioma cells.
AB  - The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small
      group of synthetic analogues. These, together with bulbispermine's natural
      crinine-type congeners, were evaluated in vitro against a panel of cancer cell
      lines with various levels of resistance to pro-apoptotic stimuli. Bulbispermine,
      haemanthamine, and haemanthidine showed the most potent antiproliferative
      activities as determined by the MTT colorimetric assay. Among the synthetic
      bulbispermine analogues, only the C1,C2-dicarbamate derivative exhibited notable
      growth inhibitory properties. All active compounds were found not to discriminate
      between the cancer cell lines based on the apoptosis sensitivity criterion; they
      displayed similar potencies in both cell types, indicating that the induction of
      apoptosis is not the primary mechanism responsible for antiproliferative activity
      in this series of compounds. It was also found that bulbispermine inhibits the
      proliferation of glioblastoma cells through cytostatic effects, possibly arising
      from rigidification of the actin cytoskeleton. These findings lead us to argue
      that crinine-type alkaloids are potentially useful drug leads for the treatment
      of apoptosis-resistant cancers and glioblastoma in particular.

PMID- 22389242
TI  - Mind your words: positive and negative items create method effects on the Five
      Facet Mindfulness Questionnaire.
AB  - Mindfulness, a construct that entails moment-to-moment effort to be aware of
      present experiences and positive attitudinal features, has become integrated into
      the sciences. The Five Facet Mindfulness Questionnaire (FFMQ), one popular
      measure of mindfulness, exhibits different responses to positively and negatively
      worded items in nonmeditating groups. The current study employed confirmatory
      factor analysis with a large undergraduate sample to examine the validity of a
      hierarchical mindfulness model and whether response patterns related to item
      wording arose from method effects. Results indicated that a correlated facets
      model better explained the data and that negative and positive wording
      constituted substantive method effects. This study suggests that the FFMQ
      measures components that may relate to, but do not seem to directly reflect, a
      latent variable of mindfulness. The authors recommend against the use of an FFMQ
      total score, favoring individual scale scores, and further examination of method
      effects in mindfulness scales.

PMID- 22389237
TI  - Dietary tocopherols inhibit cell proliferation, regulate expression of ERalpha,
      PPARgamma, and Nrf2, and decrease serum inflammatory markers during the
      development of mammary hyperplasia.
AB  - Previous clinical and epidemiological studies of vitamin E have used primarily
      alpha-tocopherol for the prevention of cancer. However, gamma-tocopherol has
      demonstrated greater anti-inflammatory and anti-tumor activity than alpha
      tocopherol in several animal models of cancer. This study assessed the potential
      chemopreventive activities of a tocopherol mixture containing 58% gamma
      tocopherol (gamma-TmT) in an established rodent model of mammary carcinogenesis.
      Female ACI rats were utilized due to their sensitivity to 17beta-estradiol (E2 )
      to induce mammary hyperplasia and neoplasia. The rats were implanted
      subcutaneously with sustained release E2 pellets and given dietary 0.3% or 0.5%
      gamma-TmT for 2 or 10 wk. Serum E2 levels were significantly reduced by the
      treatment with 0.5% gamma-TmT. Serum levels of inflammatory markers,
      prostaglandin E2 and 8-isoprostane, were suppressed by gamma-TmT treatment.
      Histology of mammary glands showed evidence of epithelial hyperplasia in E2 
      treated rats. Immunohistochemical analysis of the mammary glands revealed a
      decrease in proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX-2),
      and estrogen receptor alpha (ERalpha), while there was an increase in cleaved
      caspase 3, peroxisome proliferator-activated receptor gamma (PPARgamma), and
      nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in gamma-TmT-treated rats. In
      addition, treatment with gamma-TmT resulted in a decrease in the expression of
      ERalpha mRNA, whereas mRNA levels of ERbeta and PPARgamma were increased. In
      conclusion, gamma-TmT was shown to suppress inflammatory markers, inhibit E2 
      induced cell proliferation, and upregulate PPARgamma and Nrf2 expression in
      mammary hyperplasia, suggesting that gamma-TmT may be a promising agent for human
      breast cancer prevention.

PMID- 22389243
TI  - Psychometric properties of within-person across-session variability in accuracy
      of cognitive performance.
AB  - Although most psychological assessments are based on measures related to an
      individual's average level of performance, it has been proposed that measures of
      variability around one's average may provide unique individual difference
      information and have clinical significance. The current study investigated
      properties of within-person variability in measures of performance accuracy in a
      sample of more than 1,700 healthy adults. Contrary to what has been reported with
      measures of within-person variability in reaction time, measures of within-person
      variability in performance accuracy from different cognitive tests had weak
      correlations with one another, very low stability across time, and near-zero
      correlations with longitudinal change in cognitive abilities.

PMID- 22389244
TI  - Performance on a probabilistic inference task in healthy subjects receiving
      ketamine compared with patients with schizophrenia.
AB  - Evidence suggests that some aspects of schizophrenia can be induced in healthy
      volunteers through acute administration of the non-competitive NMDA-receptor
      antagonist, ketamine. In probabilistic inference tasks, patients with
      schizophrenia have been shown to 'jump to conclusions' (JTC) when asked to make a
      decision. We aimed to test whether healthy participants receiving ketamine would
      adopt a JTC response pattern resembling that of patients. The paradigmatic task
      used to investigate JTC has been the 'urn' task, where participants are shown a
      sequence of beads drawn from one of two 'urns', each containing coloured beads in
      different proportions. Participants make a decision when they think they know the
      urn from which beads are being drawn. We compared performance on the urn task
      between controls receiving acute ketamine or placebo with that of patients with
      schizophrenia and another group of controls matched to the patient group.
      Patients were shown to exhibit a JTC response pattern relative to their matched
      controls, whereas JTC was not evident in controls receiving ketamine relative to
      placebo. Ketamine does not appear to promote JTC in healthy controls, suggesting
      that ketamine does not affect probabilistic inferences.

PMID- 22389245
TI  - Effects of soil properties on the transfer of cadmium from soil to wheat in the
      Yangtze River delta region, China--a typical industry-agriculture transition
      area.
AB  - In order to identify the effects of soil properties on the transfer of Cd from
      soil to wheat under actual field conditions, 126 pairs of topsoil and wheat
      samples were collected from the Yangtze River delta region, China. Relevant
      parameters (Cd, Ca, Mg, Fe, Mn, Zn, N, P, K, S, pH, total organic carbon, and
      speciation of soil Cd) in soil and wheat tissues were analyzed, and the results
      were treated by statistical methods. Soil samples (19.8%) and 14.3% of the wheat
      grain samples exceeded the relevant maximum permissible Cd concentrations in
      China for agricultural soil and wheat grain, respectively. The major speciations
      of Cd in soil were exchangeable, bound to carbonates and fulvic and humic acid
      fraction, and they were readily affected by soil pH, total Ca, Mg, S and P, DTPA
      Fe, Ex-Ca, and Ex-Mg. Cadmium showed a strong correlation with Fe, S, and P
      present in the grain and the soil, whereas there was no significant correlation
      in the straw or root. Generally, soil pH, Ca, Mg, Mn, P, and slowly available K
      restricted Cd transfer from soil to wheat, whereas soil S, N, Zn, DTPA-Fe, and
      total organic carbon enhance Cd uptake by wheat.

PMID- 22389246
TI  - Asymmetric synthesis of dihydropyranones from ynones by sequential copper(I)
      catalyzed direct aldol and silver(I)-catalyzed oxy-Michael reactions.
AB  - Ynones as diene surrogates: the asymmetric synthesis of enantiomerically enriched
      substituted dihydropyranones is described. The products are obtained in two steps
      by a copper(I)-catalyzed direct aldol reaction of ynones followed by a silver
      catalyzed oxy-Michael reaction. This easy method is compatible with both aromatic
      and aliphatic substrates, and provides excellent chemoselectivity under mild
      reaction conditions.

PMID- 22389247
TI  - [Eye diseases and genetics - relevance of molecular diagnostics and research].

PMID- 22389248
TI  - [Comments of the Retinological Society, the German Ophthalmology Society and the
      Professional Union of German Ophthalmologists on epimacular brachytherapy for age
      related macular degeneration].

PMID- 22389249
TI  - Antiinflammatory properties of extracts and compounds isolated from Verbascum
      xanthophoeniceum Griseb.
AB  - Verbascum xanthophoeniceum Griseb. is an endemic plant of the Balkan region, a
      representative of the genus Verbascum used in traditional medicine for
      respiratory and inflammatory disorders. The objective of this study was to
      evaluate in vivo and in vitro the antiinflammatory action of crude extract,
      different fractions and pure compounds obtained from V. xanthophoeniceum Griseb.
      Bioactive metabolites were isolated by the use of low-pressure chromatographic
      separation. Crude methanol extract (CME) was applied in a model of paw oedema and
      different fractions and substances were tested in vitro for their effect on NO
      and cytokine production by peritoneal macrophages, and on the COX-1 and COX-2
      expression. The CME exerted inhibition on cobra venom factor (CVF)-induced oedema
      in mice, in correlation with reduced alternative pathway (AP) complement
      activity. A highly suppressive effect was expressed by nigroside VI on IL-6 and
      NO production and by forsythoside B on TNF-alpha production. Leucosceptoside B
      lowered NO release and COX-1 expression in macrophages. Verbascum
      xanthophoeniceum could serve as a promising source of active compounds with
      antiinflammatory action, particularly in complement-mediated disorders.

PMID- 22389250
TI  - Strong nuclear ring currents and magnetic fields in pseudorotating OsH4 molecules
      induced by circularly polarized laser pulses.
AB  - We design a circularly polarized laser pulse in the infrared frequency and
      femtosecond time domains, for excitation of the OsH(4) molecule in its first
      excited pseudorotational state of the triply-degenerate bend. The OsH(4) molecule
      need not be pre-oriented. After excitation, the central nucleus Os carries out
      pseudorotation about the axis parallel to the direction of propagation of the
      laser pulse. This pseudorotation causes a strong electric ring current with a
      value I=1.53 e fs(-1). The mean value of the radius of the ring current is very
      small, R=0.0031 a(0), where a(0) is the Bohr radius. According to the Biot-Savart
      law (|B(R=0)| ~I/R)), this nuclear ring current induces the strongest magnetic
      field predicted so far in molecules, with a central peak absolute value |B(R=0)|
      =623 T. To monitor the effect, we propose an IR-pump-X-ray-probe versus an X-ray
      probe-only experiment, at the K- and L-edges of X-ray ionization. The results are
      based on the general quantum theory of excitations of pseudorotations in
      tetrahedral molecules AB(4), driven by a circularly polarized laser pulse.

PMID- 22389251
TI  - Negotiating weight and body image in the UAE: strategies among young Emirati
      women.
AB  - OBJECTIVES: The goal of this study was to evaluate weight, nutritional status,
      and attitudes toward weight and health among a cohort of young women drawn from
      local populations in the United Arab Emirates. METHODS: This sample was composed
      of 103 female Emiratis, aged 18-30. Eighty of the women were students at Zayed
      University (ZU) in Dubai and 23 were students at UAE University (UAEU) in Al Ain.
      Research was divided into two phases. Methods included the collection of weight
      and height measurements (to analyze BMIs) and body fat percentages; 24-h food and
      activity recalls; semistructured, structured, and unstructured interviews; and
      participant observation. RESULTS: The distribution of BMIs in this sample was
      skewed toward underweight and normal weight in the ZU sample and split evenly
      between underweight-to-normal and overweight-to-obese in the UAEU sample, a
      finding that stands in contrast to the high rates of overweight and obesity
      reported in other age cohorts in local populations. This lower distribution of
      BMIs was correlated with widely expressed concern over body image, whereas
      reported interest in nutrition was much lower. Dietary patterns reflected
      attempts to manage weight. There was a marked trend toward nutritionally poor
      diets and sedentary living. CONCLUSIONS: Obesity and overweight among young women
      in the Emirati population do not appear to be as significant a problem as they
      are in older populations. However, several other health-related causes for
      concern emerged in this study, including extreme dieting strategies, insufficient
      micronutrient and protein intake, and widespread inactivity.

PMID- 22389252
TI  - Chemical activation of a high-affinity glutamate transporter in human
      erythrocytes and its implications for malaria-parasite-induced glutamate uptake.
AB  - Human erythrocytes have a low basal permeability to L-glutamate and are not known
      to have a functional glutamate transporter. Here, treatment of human erythrocytes
      with arsenite was shown to induce the uptake of L-glutamate and D-aspartate, but
      not that of D-glutamate or L-alanine. The majority of the arsenite-induced L
      glutamate influx was via a high-affinity, Na(+)-dependent system showing
      characteristics of members of the "excitatory amino acid transporter" (EAAT)
      family. Western blots and immunofluorescence assays revealed the presence of a
      member of this family, EAAT3, on the erythrocyte membrane. Erythrocytes infected
      with the malaria parasite Plasmodium falciparum take up glutamate from the
      extracellular environment. Although the majority of uptake is via a low-affinity
      Na(+)-independent pathway there is, in addition, a high-affinity uptake
      component, raising the possibility that the parasite activates the host cell
      glutamate transporter.

PMID- 22389253
TI  - Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in
      patients with myelodysplastic syndromes.
AB  - Mutations in genes of the splicing machinery have been described recently in
      myelodysplastic syndromes (MDS). In the present study, we examined a cohort of
      193 MDS patients for mutations in SRSF2, U2AF1 (synonym U2AF35), ZRSR2, and, as
      described previously, SF3B1, in the context of other molecular markers, including
      mutations in ASXL1, RUNX1, NRAS, TP53, IDH1, IDH2, NPM1, and DNMT3A. Mutations in
      SRSF2, U2AF1, ZRSR2, and SF3B1 were found in 24 (12.4%), 14 (7.3%), 6 (3.1%), and
      28 (14.5%) patients, respectively, corresponding to a total of 67 of 193 MDS
      patients (34.7%). SRSF2 mutations were associated with RUNX1 (P < .001) and IDH1
      (P = .013) mutations, whereas U2AF1 mutations were associated with ASXL1 (P =
      .005) and DNMT3A (P = .004) mutations. In univariate analysis, mutated SRSF2
      predicted shorter overall survival and more frequent acute myeloid leukemia
      progression compared with wild-type SRSF2, whereas mutated U2AF1, ZRSR2, and
      SF3B1 had no impact on patient outcome. In multivariate analysis, SRSF2 remained
      an independent poor risk marker for overall survival (hazard ratio = 2.3; 95%
      confidence interval, 1.28-4.13; P = .017) and acute myeloid leukemia progression
      (hazard ratio = 2.83; 95% confidence interval, 1.31-6.12; P = .008). These
      results show a negative prognostic impact of SRSF2 mutations in MDS. SRSF2
      mutations may become useful for clinical risk stratification and treatment
      decisions in the future.

PMID- 22389254
TI  - Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from
      a multicenter study.
AB  - New treatments are required for rituximab-refractory follicular lymphoma (FL). In
      the present study, patients with rituximab-refractory FL received 8 weekly
      infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg;
      N = 116). The median age of these patients was 61 years, 47% had high-risk
      Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy
      refractory, and the median number of prior therapies was 4. The overall response
      rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27
      patients refractory to rituximab monotherapy, the overall response rate was 22%.
      The median progression-free survival was 5.8 months. Forty-six percent of
      patients demonstrated tumor reduction 3 months after therapy initiation, and the
      median progression-free survival for these patients was 9.1 months. The most
      common adverse events included infections, rash, urticaria, fatigue, and
      pruritus. Three patients experienced grade 3 infusion-related reactions, none of
      which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia,
      and thrombocytopenia occurred in a subset of patients. Ofatumumab was well
      tolerated and modestly active in this heavily pretreated, rituximab-refractory
      population and is therefore now being studied in less refractory FL and in
      combination with other agents in various B-cell neoplasms. The present study was
      registered at www.clinicaltrials.gov as NCT00394836.

PMID- 22389255
TI  - The HMGA1 protoncogene frequently deregulated in cancer is a transcriptional
      target of E2F1.
AB  - Reactivation of the HMGA1 protoncogene is very frequent in human cancer, but
      still very little is known on the molecular mechanisms leading to this event.
      Prompted by the finding of putative E2F binding sites in the human HMGA1 promoter
      and by the frequent deregulation of the RB/E2F1 pathway in human carcinogenesis,
      we investigated whether E2F1 might contribute to the regulation of HMGA1 gene
      expression. Here we report that E2F1 induces HMGA1 by interacting with a 193 bp
      region of the HMGA1 promoter containing an E2F binding site surrounded by three
      putative Sp1 binding sites. Both gain and loss of function experiments indicate
      that Sp1 functionally interacts with E2F1 to promote HMGA1 expression. However,
      while Sp1 constitutively binds HMGA1 promoter, it is the balance between
      different E2F family members that tunes the levels of HMGA1 expression between
      quiescence and proliferation. Finally, we found increased HMGA1 expression in
      pituitary and thyroid tumors developed in Rb(+/-) mice, supporting the hypothesis
      that E2F1 is a novel important regulator of HMGA1 expression and that
      deregulation of the RB/E2F1 path might significantly contribute to HMGA1
      deregulation in cancer.

PMID- 22389256
TI  - Frequency, clinical presentation, and outcomes of drug-induced liver injury after
      liver transplantation.
AB  - Drug-induced liver injury (DILI) is increasingly being recognized as a common
      cause of acute hepatitis. The clinical impact of DILI after liver transplantation
      (LT) is not known. The aim of this study was to describe the frequency, clinical
      presentation, and outcomes of DILI in LT recipients. LT recipients with possible
      DILI were identified with electronic pathology records and clinical note database
      retrieval tools. Diagnostic criteria were applied to identify cases of DILI.
      Twenty-nine of 1689 LT recipients (1.7%) were identified with DILI. The mean age
      was 52 years, and 52% were women. The major indications for LT were primary
      sclerosing cholangitis (28%), cholangiocarcinoma (14%), and hepatocellular
      carcinoma (14%). The severity of DILI was mild or moderate in 92% of the cases.
      Nausea or diarrhea (31%), jaundice (24%), and pruritus (10%) were the most common
      symptoms at the time of diagnosis. The mean biochemistry values were as follows:
      alanine aminotransferase, 204 +/- 263 U/L; aspartate aminotransferase, 108 +/-
      237 U/L; alkaline phosphatase, 469 +/- 689 U/L; and total bilirubin, 1.9 +/- 10.3
      mg/dL. The median duration of medication use until the diagnosis of DILI was 57
      days, and the major agent classes were antibiotics (48%), immunosuppressive
      agents (14%), and antihyperlipidemic drugs (7%). Trimethoprim-sulfamethoxazole
      was the most common implicated agent (n = 11). Serum liver enzymes improved
      within a median time of 34 days (range = 5-246 days) after drug withdrawal.
      Hepatic retransplantation or death did not occur. Among the 50 cases with
      possible DILI explained by other causes, 13 individuals (26%) had no alternative
      diagnosis despite histological findings compatible with DILI. In conclusion, DILI
      is a rare yet underrecognized event among LT recipients. The majority of cases
      are not clinically severe, and they resolve after drug cessation without hepatic
      retransplantation or death.

PMID- 22389257
TI  - Effect of steatosis donor liver transplantation on hepatocellular carcinoma
      recurrence: experience at a single institution.
AB  - BACKGROUND/AIMS: The increasing demand for transplantation has led application of
      steatotic liver as the graft. The aim of this study was to determine the effect
      of donor graft steatosis on overall outcome and tumor recurrence after liver
      transplantation for hepatocellular carcinoma. METHODOLOGY: 131 patients that
      underwent liver transplantation for hepatocellular carcinoma between 2007 and
      2008 were included. Donor steatosis was categorized as non-steatosis group (0%
      10%, n=101) and steatosis group (>10%, n=30). The Kaplan-Meier method and Cox
      proportional hazard regression model was used for data analysis. RESULTS:
      Postoperative recipient survival rate was 81% and 66.6% at 1 and 3 years,
      respectively, for non-steatotic graft; 87.5% and 58.3% for mild steatosis; 83.3%
      and 41.7% for moderate to severe steatosis (p=0.303). Postoperative tumor
      recurrence rate was 15.8% and 28.7% at 1 and 3 years, respectively, for grafts
      with no steatosis; 8.3% and 20.8% for those with mild steatosis; 33.3% and 50%
      for those with moderate to severe steatosis, (p>0.05). CONCLUSIONS: Steatotic
      donor was not associated with a worse prognosis in early stage postoperative and
      mild fatty liver did not increase tumor recurrence risks. The moderate to severe
      status of fatty liver had some effect on tumor recurrence.

PMID- 22389258
TI  - Isolable tris(alkyne) and bis(alkyne) complexes of gold(I).
AB  - Golden trefoils: Tris(alkyne)gold complex [(coct)(3)Au][SbF(6)] (see picture; 1
      SbF(6)) can be synthesized from cyclooctyne (coct) and AuSbF(6) generated in
      situ. Treatment of AuCl with cyclooctyne led to the bis(alkyne)gold complex
      [Au(coct)(2)Cl] (2). DFT analysis indicates that the cyclooctyne ligands are net
      electron donors in 1 but overall electron acceptors in 2. AuSbF(6) is shown to
      mediate [2+2+2] cycloaddition reactions of alkynes.

PMID- 22389259
TI  - Undirected arene and chelate-assisted olefin C-H bond activation: [Rh(III)Cp*]
      catalyzed dehydrogenative alkene-arene coupling as a new pathway for the
      selective synthesis of highly substituted Z olefins.

PMID- 22389260
TI  - [Removal of centrally located subretinal perfluorocarbon liquid].
AB  - BACKGROUND: Subretinal perfluorocarbon liquid (PFCL) droplets are occassionally
      seen after vitreoretinal surgery for retinal detachment. Usually they are located
      peripherally without causing complications and therapeutic consequences. In
      contrast, centrally located PFCL droplets affect final visual outcomes. In animal
      experiments subretinal PFCL has caused direct toxic effects on photoreceptor
      cells and retinal pigment epithelium. PATIENTS AND METHODS: We report about the
      rare event of a centrally located subretinal PFCL droplet in 2 patients, their
      surgical removal and functional outcome. In both patients a PFCL droplet remained
      subretinally after primary vitrectomy for a rhegmatogenous retinal detachment. In
      patient 1 the PFCL droplet was located subfoveally for 6 weeks, in patient 2
      underneath the papillomacular bundle for 8 weeks causing severe visual loss. In
      both patients the PFCL was removed transretinally through a 32 gauge cannula.
      Vision and central scotoma improved in both patients markedly. No complications
      due to the mini-retinotomy could be observed. CONCLUSION: Centrally located PFCL
      droplets are decreasing vision and should be surgically removed. A transretinal
      removal of subretinal PFCL droplets is possible and the iatrogenic damage seems
      acceptable.

PMID- 22389261
TI  - [Dopamine receptors of the corneal epithelium and endothelium].
AB  - BACKGROUND: Dopamine is a major neurotransmitter and its two receptor subgroups,
      termed D1-like and D2-like receptors, are found both in the central and
      peripheral nervous systems. D1-like receptors signal through increases, D2-like
      receptors through decreases in cAMP production. Reports about the presence of
      dopamine receptors in the cornea are rare and inconsistant. The aim of this study
      was to examine if native bovine corneal epithelial and endothelial cells express
      dopamine receptors and whether these receptors belong to the D1-like or D2-like
      group. MATERIALS AND METHODS: Dopamine receptors were studied using polyclonal
      antibodies. The cAMP concentration after receptor stimulation with dopamine was
      determined by means of an enzyme immunoassay. RESULTS: In bovine corneal
      epithelium and endothelium immunohistochemical staining was positive for D1-like
      receptors but not for D2-like receptors. Stimulation of corneal D1-like receptors
      with dopamine revealed a dose-dependent increase of the intracellular cAMP
      concentration which was blocked by SCH23 390 (a selective D1-like antagonist).
      CONCLUSION: Our data demonstrate that bovine corneal epithelium and endothelium
      express a functional D1-like receptor positively coupled to adenylyl cyclase and
      cAMP production. However, at the present time the physiological role of this
      receptor remains a matter of speculation.

PMID- 22389262
TI  - Photodynamic therapy in the treatment of persistent central serous
      chorioretinopathy: a two-year follow-up.
AB  - BACKGROUND: The aim of this study was to assess during a follow-up period of two
      years the efficacy and safety of photodynamic therapy (PDT) in central serous
      chorioretinopathy (CSC) showing no spontaneous resolution four months after the
      onset of the symptoms. PATIENTS AND METHODS: We present a prospective
      interventional non-comparative case series. The diagnosis of CSC was confirmed by
      fluorescein angiography (FA), and optical coherence tomography (OCT) in 46 eyes
      of 42 consecutive patients. PDT was performed according to the protocol used for
      treating choroidal neovascularization in age-related macular degeneration. The
      primary end point was to assess the anatomic re-attachment of the retina. The
      secondary end point was to record the visual function. A paired t-test and a
      linear regression and correlation test were used for the statistics. RESULTS: The
      leakage in FA and the detachment of the neurosensory retina in OCT were no longer
      present in 42 eyes six weeks after PDT and in the remaining four eyes three
      months after PDT. At the end of the follow-up, the best-corrected visual acuity
      measured with an ETDRS chart improved in 36 eyes, and remained stable in 10 eyes
      (mean improvement, 10.2 letters; p < 0.001). Two cases of recurrence were
      diagnosed. No treatment-related complications were noticed. CONCLUSIONS: PDT
      could be an effective and durable option for treating patients with persistent
      CSC.

PMID- 22389263
TI  - [Diagnosis of conjunctival neoplastic lesions by confocal in-vivo microscopy].
AB  - BACKGROUND: There is a wide spectrum of benign and malignant conjunctival
      neoplastic lesions that are often impossible to distinguish clinically by slit
      lamp microscopy. The current study was undertaken to compare in-vivo confocal
      laser scanning microscopy (CLSM) and histology for the preoperative assessment of
      benign or malignant status. CASE REPORTS: We present the clinical details of
      three patients. In two cases the neoplastic lesions were classified as benign
      (actinic keratosis). In-vivo CLSM revealed densely layered, sometimes
      hyperreflective conjunctival epithelial cells, together with multiple
      inflammatory cells and microcysts. Correlated findings on histology showed
      keratinisation with inflammatory infiltrates and intracellular oedema formation.
      In-vivo CLSM images in the third patient revealed interruptions of the layered
      epithelial structure with regular conjunctival epithelium co-existing with
      complexes of enlarged cells with polymorphic nuclei. Histology also showed an
      abrupt transition from regular squamous epithelium to hyperplastic, dysplastic
      squamous epithelium. In this case the neoplastic lesion was classified as
      carcinoma in situ. DISCUSSION: The in-vivo CLSM images correlated positively with
      histology findings. Although in-vivo CLSM offers the capability to perform non
      invasive examinations over time, associated histological assessment (because of
      its more precise detail and additional staining techniques) remains indispensable
      for planning further action and determining the prognosis.

PMID- 22389264
TI  - Characteristics of Killian-Jamieson diverticula mimicking a thyroid nodule.
AB  - BACKGROUND: Killian-Jamieson (K-J) diverticula have been incidentally detected on
      neck ultrasonography and could be misdiagnosed as thyroid nodules. The purpose of
      this study was to define the clinical and ultrasonographic characteristics of K-J
      diverticula. METHODS: We analyzed 13 patients with K-J diverticula mimicking
      thyroid nodules including 4 of our patients and 11 previously reported cases
      between 1984 and August 2009. RESULTS: Seven patients (54%) were women, and all
      patients were asymptomatic. The average lesion's diameter was 1.5 cm (range, 0.5
      4.0). Most of the lesions (92%) were located in the left thyroid lobe.
      Ultrasonography showed heterogeneous echogenic masses with echogenic foci and
      hypoechoic rims. A connection with the adjacent esophageal wall was found in 7
      diverticula (54%) at the time of initial diagnosis. CONCLUSION: The K-J
      diverticula had unique ultrasonographic findings. Awareness of the fact that K-J
      diverticula can be misdiagnosed as thyroid nodules is important to avoid
      unnecessary interventions.

PMID- 22389265
TI  - Extraction of a headscarf pin from the vertebral artery without embolization.
AB  - BACKGROUND: Foreign bodies traversing the aerodigestive tract lining into the
      surrounding soft tissues is a well-known entity. A 14-year-old girl was referred
      to our hospital after swallowing a pin that was not visualized by laryngoscopy,
      despite a neck film that localized it to the level of the larynx. METHODS: A CT
      scan demonstrated a bent pin piercing the left vertebral artery "through and
      through," and this was confirmed by angiography. The pin was extracted via an
      external approach to the neck without preoperative intravascular manipulation.
      RESULTS: Angiography immediately after the surgery demonstrated a stable
      thrombotic sleeve in the vertebral artery without further clot propagation or
      bleeding from the vessel wall. This is the first report of a "through and
      through" thrombotic sleeve in an artery. CONCLUSIONS: Simple surgical removal of
      a sharp foreign body from the vertebral artery without intravascular management
      may be a reasonable option.

PMID- 22389267
TI  - Clinicopathological feature of extrahepatic cholangiocarcinoma without jaundice:
      a single-center experience.
AB  - BACKGROUND/AIMS: The prognosis remains unsatisfactory even if the patient
      undergoes extensive surgery, which is the only curative treatment for these
      tumors. Therefore, early detection and diagnosis are needed to improve long-term
      survival. To investigate the clinicopathological feature of extrahepatic
      cholangiocarcinoma in patients presenting without jaundice compared with the
      features of tumors in patients presenting with jaundice. METHODOLOGY: This was a
      retrospective study of 50 patients resected for extrahepatic cholangiocarcinoma.
      There were 15 non-jaundiced (Group A) and 35 jaundiced patients (Group B). Data
      on demographic and clinical features, surgical procedures and pathological
      diagnoses were collected retrospectively. RESULTS: Preoperative mean serum levels
      of total bilirubin, aspartate aminotransferase, alanine aminotransaminase,
      alkaline phosphatase and gamma-glutamyltranspeptidase were statistically
      different between the groups. There was also a significant difference in the
      location of tumors. The distal tumors occurred in 9 non-jaundiced and 31
      jaundiced patients (p=0.048). There were no significant differences between the
      characteristics and preoperative laboratory data of the patients with perihilar
      tumors and those with distal tumors. CONCLUSIONS: We believe that finding the
      disease in asymptomatic and non-jaundiced patients is very important for their
      prognosis. Further studies are needed and efforts should also continue to
      identify patients with suspicious findings.

PMID- 22389266
TI  - Bioactive tanshinone I inhibits the growth of lung cancer in part via
      downregulation of Aurora A function.
AB  - Lung cancer is the leading cause of cancer death in the world, and the searching
      for novel efficacious and safe agents for lung cancer prevention remains the top
      priority of lung cancer research. In the present study, we evaluated the effect
      of bioactive tanshinones from a Chinese herb Salvia miltiorrhiza,
      cryptotanshinone (CT), tanshinone I (T1) and tanshinone IIA (T2A), on the
      proliferation inhibition of lung cancer cell lines. Tanshinones inhibited the
      lung cancer cell proliferation in vitro, with T1 the most potent, via cell cycle
      arrest and apoptosis induction. Gene function assay showed that Aurora A
      knockdown by siRNA dramatically eliminated the T1 activity in vitro, suggesting
      that Aurora A is an important functional target for T1. We further evaluated the
      effectiveness of T1 on the growth of H1299 nonsmall lung cancer cell in a mouse
      model. Tanshinone I inhibited the growth of H1299 lung tumor in a dose-dependent
      manner. Tanshinone I at 200 mg/kg body weight significantly reduced final tumor
      weight by 34% (P < 0.05) associated with inhibiting proliferation and inducing
      apoptosis of lung cancer cells by 54% (P < 0.001) and 193% (P < 0.001),
      respectively, inhibiting lung tumor angiogenesis by 72% (P < 0.001), and reducing
      Aurora A expression by 67% (P < 0.001). On the other hand, T1 did not
      significantly alter food intake or body weight. Our results provided experimental
      evidence to suggest that T1 may be an efficacious and safe agent for the
      prevention of lung cancer progression and Aurora A may be an important molecular
      target for T1 action against lung cancer.

PMID- 22389268
TI  - Comparing of the results between single port and three ports in laparoscopic
      cholecystectomy.
AB  - BACKGROUND/AIMS: The aim of this prospective trial was to observe the results of
      the two types of techniques. METHODOLOGY: Single port laparoscopic
      cholecystectomy (SPLC) (56 cases) indication was polyp disease and mild
      cholecystitis with gall bladder stone (no right upper quadrant tenderness in
      physical examination, no gall bladder wall thickening in image study). Three
      ports laparoscopic cholecystectomy (TPLC) (46 cases) was applied to previous
      laparoscopic surgery indication. There were slight differences in indication as
      there are still limitations in applying single port laparoscopic cholecystectomy
      in all patients. RESULTS: The two groups were similar with respect to demographic
      characteristics. There were no significant differences in operation time, bile
      leakage during operation, postoperative hospital stay, pain score. Additional
      port(s) use in single port laparoscopic cholecystectomy were 13 cases, the
      reasons were difficult dissection of Calot's triangle (7 cases), incomplete
      ligation by Hem-o-lok clip (3 cases), cystic artery bleeding (3 cases), difficult
      visual due to obesity (1 case). CONCLUSIONS: Single port laparoscopic
      cholecystectomy is still in its initial stages. Although many controversies
      remain regarding stability and possibility, it is believed that development and
      exchange of new instruments and techniques will form an important part of future
      minimal invasive surgery.

PMID- 22389269
TI  - Transanal endoscopic microsurgery: a Brazilian initial experience in private
      practice.
AB  - BACKGROUND/AIMS: Transanal endoscopic microsurgery is a minimally invasive
      approach for rectal lesions. Superior exposure and access to the entire rectum
      result in lesser risk of compromised margin and lower recurrence rates compared
      to conventional transanal excision. It was aimed at describing a single
      institution's initial experience with transanal endoscopic microsurgery.
      METHODOLOGY: Retrospective review of a prospective database. Fifty-two procedures
      from March 2009 to November 2011 were analyzed. RESULTS: Fifty operations were
      completed. There were 23 men. Mean age was 67.5 (42-89). Mean follow-up was 23 (1
      31) months. Average tumor size was 4.8 cm (1.5-14 cm). Mean distance from anal
      verge was 6 (3-15) cm. Mean operating time was 110 (86-170) min. Postoperative
      complication rate was 16%o. There were no re-admissions. Mortality was null.
      Operative pathology was adenoma in 25, in situ adenocarcinoma in eight, invasive
      adenocarcinoma in 13, neuroendocrine carcinoma in three and no residual lesion in
      one case. Recurrence was 4% for benign and 8% for malignant tumors. CONCLUSIONS:
      TEM is a minimally invasive procedure with low postoperative morbidity during
      initial experience. TEM is curative for benign lesions and for selected early
      cancers. It is useful after neoadjuvant therapy for strictly selected cancers
      while the results of multi-institutional trials are awaited.

PMID- 22389270
TI  - Current situation of endoscopic treatment for common bile duct stones.
AB  - BACKGROUND/AIMS: The progression of endoscopy and devices as well as newly
      developed treatment methods have enabled endoscopic lithotomy. In this study, we
      examined to what degree is it possible to endoscopically treat patients who are
      diagnosed as having common bile duct stones. METHODOLOGY: Lithotomy was conducted
      using a backward side-viewing endoscope for patients without surgical history of
      upper gastrointestinal tract and patients with stomach reconstructed with
      Billroth-I method, using an ordinary endoscope for patients with stomach
      reconstructed with Billroth-II method (Bil-II) and using a double balloon
      endoscope for patients with difficulty in reaching the papilla or patients of
      Roux-en-Y anastomosis (R-Y). As for treatment methods, we selected endoscopic
      sphincterotomy as the first choice for papilla treatment and selected endoscopic
      papillary balloon dilation for patients with bleeding tendency or patients of Bil
      II or R-Y. For patients with multiple stones or giant stones, lithotripsy was
      selected depending on judgment of the endoscopist. RESULTS: Endoscopic complete
      lithotomy was successful in 97.7% (168/172). An accidental disease was observed
      in 2.9% (5/172). In one patient with the perforated gastrointestinal tract, a
      surgery was performed but others were mild. CONCLUSIONS: Common bile duct stones
      can be endoscopically treated safely with high rate.

PMID- 22389271
TI  - Correlation between spiral CT preoperative staging of pancreatic cancer and PTEN
      and COX-2 expression.
AB  - BACKGROUND/AIMS: The aim of the present study was to evaluate the efficacy of TNM
      staging of pancreatic cancer by multilayer spiral computed tomography (MSCT) and
      its correlation with tissue PTEN and COX-2 expression. METHODOLOGY: Fifty-two
      patients with pancreatic cancer had MSCT for TNM staging and PTEN and COX-2
      expression were detected in pancreatic cancer tissue by immunohistochemistry.
      RESULTS: The total accuracy of MSCT was 79.5% in diagnosis of TMN staging of
      pancreatic cancer, with 73.1% for T staging (70.0% in T1, 65.0% in T2, 82.4% in
      T3 and 80.0% in T4), 76.9% for N staging (81.8% in N0 and 73.3% in N1) and 88.5%
      for M staging (89.7% in M0 and 84.6% in M1). The PTEN expression was not related
      to tumor size (p>0.05) but correlated with T staging, lymph node metastasis and
      clinical staging (p<0.05). COX-2 expression was not related to tumor size and T
      staging (p>0.05) but correlated with lymph node metastasis and clinical staging
      (p<0.05). CONCLUSIONS: TNM staging of pancreatic cancer was accurately conducted
      by MSCT-thin-layer-imaging. The correlation with PTEN and COX-2 expression
      implied that combined application of both approaches can improve the accuracy of
      diagnosis and staging in pancreatic cancer.

PMID- 22389272
TI  - Health-related quality of life of liver transplant recipients: a single center
      experience.
AB  - BACKGROUND/AIMS: To evaluate the health related quality of life (HRQOL) of liver
      transplant recipients and to identify risk factors influencing post-operative
      HRQOL. METHODOLOGY: Adult patients who underwent primary liver transplantation
      from 2009 to 2010 were asked to complete a HRQOL survey at pre-operation and one
      year postoperatively. We compared the HRQOL of liver transplant recipients at pre
      transplantation and one year postoperatively to the general population. Pre
      transplant variables were analyzed to identify the risk factors influencing
      postoperative HRQOL. RESULTS: Pre-transplant HRQOL was significantly lower than
      that of the general population and significantly improved at one year
      postoperatively. Multivariate analyses suggested hepatocellular carcinoma, pre
      transplant hypertension and high model for end-stage liver disease score were
      independent risk factors for postoperative physical component summary (PCS); and
      higher education level, marital status and lower income level negatively impacted
      on the postoperative mental component summary (MCS). CONCLUSIONS: Factors
      influencing postoperative HRQOL were identified in the present study. Transplant
      centers should pay more attention to patients with above-mentioned risk factors
      and strive to improve the HRQOL.

PMID- 22389273
TI  - A Phase III trial to evaluate the effect of perioperative nutrition enriched with
      eicosapentaenoic acid on body weight loss after total gastrectomy for T2-T4a
      gastric cancer.
AB  - This randomized Phase III trial will evaluate whether perioperative nutrition
      enriched with eicosapentaenoic acid can prevent body weight loss after total
      gastrectomy for gastric cancer. The patients who enroll in this study will be
      randomly assigned to Group A: no supplementation with oral nutrients (standard
      diet) or Group B: standard diet with eicosapentaenoic acid-enriched
      supplementation for 7 days before surgery and for 21 days after surgery. For both
      groups, patients will undergo total gastrectomy with Roux-en Y reconstruction.
      The extent of dissection will principally follow the third edition of the Gastric
      Cancer Treatment Guideline published by the Japanese Gastric Cancer Association.
      When patients are diagnosed with pathological Stage II or III disease, adjuvant
      chemotherapy with S-1 will be initiated within 6 weeks after surgery and
      administered for 1 year. The primary endpoint will be the body weight loss at 1
      and 3 months after surgery (double primary endpoints). The secondary endpoints
      will be the relative performance of the supplement, loss of lean body mass at 1
      and 3 months after surgery, the lowest serum albumin level, quality of life, the
      incidence of surgical morbidity and mortality, and the incidence of surgical site
      infection.

PMID- 22389274
TI  - Prognostic significance of diabetes mellitus in localized renal cell carcinoma.
AB  - OBJECTIVE: We investigated whether diabetes mellitus is associated with the
      cancer-related outcomes in patients with localized clear cell renal cell
      carcinoma treated with radical or partial nephrectomy. METHODS: We reviewed data
      from 950 patients who received radical or partial nephrectomy for localized clear
      cell renal cell carcinoma from 1988 to 2009. We analyzed potential association of
      patients' diabetic status and various clinicopathologic features. Univariate and
      multivariate analyses were performed to identify independent predictors of cancer
      specific survival, overall survival and non-cancer-related survival. RESULTS: Of
      950 patients, 108 (11.4%) reported having diabetes mellitus pre-operatively.
      Patients with and without diabetes mellitus demonstrated no significant
      differences regarding various clinicopathologic features except for age (P <
      0.001), pre-existing hypertension (P < 0.001), pre-existing cardiovascular
      disease (P < 0.001) and performance status (P = 0.019). In terms of cancer
      specific, overall and non-cancer-related survival, the Kaplan-Meier curves showed
      that non-diabetic patients had superior survival rates than diabetics (P = 0.012,
      <0.001 and <0.001, respectively). Meanwhile, although diabetes mellitus was shown
      to be an independent predictor of overall survival (P = 0.022) and non-cancer
      related survival (P = 0.034), it was not observed to be a significant predictor
      of cancer-specific survival (P = 0.234) in multivariate analyses. CONCLUSIONS:
      Diabetes mellitus may not be directly associated with disease-specific outcome in
      patients who receive surgical management for localized renal cell carcinoma.
      However, since diabetes mellitus was observed to be associated with overall
      survival in such patients, diabetic patients undergoing surgery for localized
      renal cell carcinoma should be counseled on the potential impact of diabetes
      mellitus.  Institutional review board (IRB) approval number H-1106-062-366.

PMID- 22389275
TI  - Solitary skin metastasis adjacent to ureterocutaneostomy 4 years after radical
      cystectomy for bladder cancer.
AB  - A 65-year-old Japanese woman underwent radical cystectomy and right
      nephroureterectomy for muscle-invasive bladder cancer. A left ureterocutaneostomy
      was constructed for urinary diversion. There was no evidence of recurrence for 4
      years after the surgery. At 54 months after the surgery, however, she was
      referred with a chief complaint of painless skin erosion around the stoma. An
      incisional biopsy of the lesion showed no evidence of malignancy. Thereafter, the
      lesion was treated as a benign skin erosion. However, the erosion expanded over
      the next 4 months, and a second incisional biopsy revealed that the erosion was
      overlying malignant cells. Computed tomography showed a skin tumor of 4 cm in
      diameter. No other metastases were revealed on whole-body imaging examinations.
      Urine cytology was negative. A skin tumor extirpation was performed, and the
      specimen showed that the skin tumor consisted of malignant growth of papillary
      cells adjacent to the ureter, which were identical to those of the primary
      bladder cancer. A malignant component was not observed in the lumen of the
      resected ureter. No evidence of disease was observed in the first 3 months after
      extirpation. Reports of solitary skin metastasis from bladder cancer are rare,
      and only a few cases have been reported in the English literature. Because skin
      metastasis from bladder cancer can mimic a number of different benign conditions,
      a high index of suspicion may be necessary to make a definitive diagnosis.

PMID- 22389276
TI  - Electron transfer to benzenes by photoactivated neutral organic electron donor
      molecules.

PMID- 22389277
TI  - The morphology and phylogeny of two euplotid ciliates, Diophrys blakeneyensis
      spec. nov. and Diophrys oligothrix Borror, 1965 (Protozoa, Ciliophora,
      Euplotida).
AB  - The morphology, infraciliature and molecular phylogeny of two marine ciliated
      protozoans, Diophrys blakeneyensis spec. nov. and Diophrys oligothrix Borror,
      1965, isolated from British salt marshes, were investigated using microscopic
      observations of live and protargol-impregnated specimens, and by small subunit
      (SSU) rRNA gene sequence analysis. Diophrys blakeneyensis spec. nov. is
      characterized as follows: cell oval to rectangular in outline; size variable,
      approximately 60-180 * 30-80 um in vivo; adoral zone comprising about 45
      membranelles; usually five frontal, two ventral, five transverse, two left
      marginal and three caudal cirri; five dorsal kineties with more than 10
      dikinetids each; 7-23 spherical to ellipsoid macronuclear nodules in a ring-like
      pattern; marine biotope. The population of Diophrys oligothrix described here
      corresponds well with previous populations in terms of its general morphology and
      ciliary pattern, in particular the continuous ciliary rows on the dorsal side
      with loosely arranged cilia. The main differences between the present and
      previously reported populations are the broader buccal field and greater number
      of dorsal kineties in the present population, both of which are regarded as
      population-dependent features. Phylogenetic analyses based on SSU rRNA gene
      sequence data demonstrate that Diophrys blakeneyensis is most closely related to
      Diophrys oligothrix, and both organisms cluster with two congeners with high
      bootstrap support within a larger group that contain the core species of the
      Diophrys-complex. Cladistic analysis based on morphological and morphogenetic
      data broadly agree with the SSU rRNA gene sequence phylogeny. Both analyses
      suggest that the genus Diophrys may be polyphyletic.

PMID- 22389278
TI  - Loktanella litorea sp. nov., isolated from seawater.
AB  - A Gram-negative, non-motile, rod-shaped bacterial strain, designated DPG-5(T),
      was isolated from seawater of the South Sea, Korea and subjected to a study using
      a polyphasic taxonomic approach. Strain DPG-5(T) grew optimally at pH 7.0-8.0, at
      30  degrees C and in the presence of 2 % (w/v) NaCl. Neighbour-joining
      phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DPG
      5(T) fell within the clade comprising members of the genus Loktanella, and formed
      a cluster with the type strains of Loktanella rosea, Loktanella maricola,
      Loktanella koreensis and Loktanella tamlensis, with which it exhibited highest
      16S rRNA gene sequence similarity values of 96.7, 96.5, 96.2 and 96.7 %,
      respectively. The 16S rRNA gene sequence similarity values between strain DPG
      5(T) and the type strains of the other species of the genus Loktanella were in
      the range of 94.4-96.0 %. The DNA G+C content of strain DPG-5(T) was 57.6 mol%.
      Strain DPG-5(T) contained Q-10 as the predominant ubiquinone and C(18 : 1)omega7c
      and 11-methyl C(18 : 1)omega7c as the major fatty acids. The major polar lipids
      found in strain DPG-5(T) were phosphatidylcholine and phosphatidylglycerol.
      Differential phenotypic properties, together with the phylogenetic
      distinctiveness, showed that strain DPG-5(T) is differentiated from other species
      of the genus Loktanella. On the basis of the data presented, strain DPG-5(T) is
      considered to represent a novel species of the genus Loktanella, for which the
      name Loktanella litorea sp. nov. is proposed. The type strain is DPG-5(T) (= KCTC
      23883(T) = CCUG 62113(T)).

PMID- 22389279
TI  - Rhodobacter viridis sp. nov., a phototrophic bacterium isolated from mud of a
      stream.
AB  - A green phototrophic bacterium (strain JA737(T)), which was oval- to rod-shaped,
      Gram-negative and motile, was isolated from mud of a stream in the Western Ghats
      of India. Strain JA737(T) contained bacteriochlorophyll a, and the major
      carotenoid was neurosporene. The major quinone was Q-10 and the polar lipids were
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an
      unidentified aminolipid, two unidentified phospholipids and five unidentified
      lipids. Phylogenetic analysis showed that the strain clustered with members of
      the genus Rhodobacter belonging to the family Rhodobacteraceae of the class
      Alphaproteobacteria. Based on 16S rRNA gene sequence analysis, strain JA737(T)
      had highest sequence similarity with Rhodobacter capsulatus ATCC 11166(T) (98.8
      %), Rhodobacter maris JA276(T) (97 %), Rhodobacter aestuarii JA296(T) (96.7 %)
      and other members of the genus Rhodobacter (<96 %). However, strain JA737(T)
      showed 22-55 % DNA-DNA relatedness with the above type strains. On the basis of
      phenotypic, chemotaxonomic and molecular genetic evidence, strain JA737(T)
      represents a novel species of the genus Rhodobacter, for which the name
      Rhodobacter viridis sp. nov. is proposed. The type strain is JA737(T) ( = KCTC
      15167(T) = MTCC 11105(T) = NBRC 108864(T)).

PMID- 22389280
TI  - Pseudogulbenkiania gefcensis sp. nov., isolated from soil.
AB  - A novel strain, yH16, was isolated on nutrient agar from soil samples collected
      at KyungHee University, Suwon City, Republic of Korea. Cells of strain yH16(T)
      were short rods, Gram-negative-staining, motile and non-spore-forming, with a
      polar flagellum. Biochemical and molecular characterization revealed that this
      strain was most similar to Pseudogulbenkiania subflava BP-5(T). Further 16S rRNA
      gene sequencing studies revealed that the new strain clustered with
      Pseudogulbenkiania subflava BP-5(T) (95.9 % similarity), Paludibacterium
      yongneupense 5YN8-15(T) (95.2 % similarity), Gulbenkiania mobilis E4FC31-5(T)
      (94.6 % similarity) and Chromobacterium aquaticum CC-SE-YA-1(T) (93.9 %
      similarity). The isolate was able to grow at 25-40  degrees C, 0.3-2 % NaCl and
      pH 5.5-7. The DNA G+C content was 65.9 +/- 1.0 mol%. The predominant fatty acids
      were summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH) and C(16:0).
      Ubiquinone 8 was the major respiratory quinone. It was evident from the data
      obtained that the strain should be classified as a novel species of the genus
      Pseudogulbenkiania. The name proposed for this taxon is Pseudogulbenkiania
      gefcensis sp. nov., and the type strain is yH16(T) (=KCCM 90100(T) = JCM
      17850(T)).

PMID- 22389281
TI  - Nonomuraea jabiensis sp. nov., isolated from arid soil.
AB  - A novel actinomycete, strain A4036(T), was isolated from a soil sample collected
      from the Jabi district in Abuja, Nigeria. The taxonomic position of strain
      A4036(T) was established using a combination of genotypic and phenotypic
      analyses. The organism formed extensively branched substrate and aerial hyphae
      that generated spiral chains of spores with warty surfaces. The cell wall
      contained meso-diaminopimelic acid and the cell-wall sugars were glucose,
      madurose, mannose and ribose. The predominant menaquinone was MK-9(H(4)). The
      polar lipids were diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylinositol
      mannoside, hydroxy-phosphatidylethanolamine, hydroxy
      phosphatidylmethylethanolamine, two unidentified phospholipids and four unknown
      glucosamine-containing phospholipids. The major cellular fatty acids were iso
      C(16 : 0) 2-OH, iso-C(16 : 0) and 10-methyl C(17 : 0). On the basis of 16S rRNA
      gene sequence similarity studies, strain A4036(T) grouped in the genus
      Nonomuraea, being most closely related to Nonomuraea angiospora IFO 13155(T)
      (99.05 %), Nonomuraea candida HMC10(T) (98.78 %), Nonomuraea kuesteri GW 14
      1925(T) (98.49 %), Nonomuraea endophytica YIM 65601(T) (98.42 %), Nonomuraea
      maheshkhaliensis 16-5-14(T) (98.40 %), Nonomuraea turkmeniaca DSM 43926(T) (98.38
      %), Nonomuraea helvata IFO 14681(T) (98.29 %), Nonomuraea rubra DSM 43768(T)
      (98.10 %) and Nonomuraea salmonea DSM 43678(T) (98.06 %). Levels of 16S rRNA gene
      sequence similarity to the type strains of other species of the genus Nonomuraea
      were <98 %. Despite the high 16S rRNA gene sequence similarities, DNA-DNA
      relatedness values and phenotypic data demonstrated that strain A4036(T) was
      clearly distinguished from all closely related species of the genus Nonomuraea.
      Thus, this isolate is considered to represent a novel species of the genus
      Nonomuraea, for which the name Nonomuraea jabiensis sp. nov. is proposed. The
      type strain is A4036(T) (= DSM 45507(T) = KCTC 19870(T)).

PMID- 22389282
TI  - Rhodopseudomonas pentothenatexigens sp. nov. and Rhodopseudomonas thermotolerans
      sp. nov., isolated from paddy soils.
AB  - Two strains (JA575(T) and JA576(T)) of orange- to pink-pigmented, rod-shaped,
      motile and budding phototrophic bacteria were isolated from paddy soils. Both
      strains contained bacteriochlorophyll a and carotenoids of spirilloxanthin
      series. Both strains had C(18 : 1)omega7c as the major cellular fatty acid,
      ubiquinone-10 (Q(10)) as the main quinone, and diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine as polar
      lipids. Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that
      both strains clustered with species of the genus Rhodopseudomonas in the class
      Alphaproteobacteria. Strains JA575(T) and JA576(T) were genotypically (<35 % DNA
      DNA relatedness) and phenotypically distinct from each other. Further, both
      strains showed less than 48 % DNA-DNA relatedness with the type strains of all
      recognized species of the genus Rhodopseudomonas. The molecular evidence is
      supported by phenotypic evidence. It is proposed that strains JA575(T) and
      JA576(T) be classified as representing two novel species of the genus
      Rhodopseudomonas with the species names Rhodopseudomonas pentothenatexigens sp.
      nov. and Rhodopseudomonas thermotolerans sp. nov., respectively. The type strains
      of the proposed novel species are JA575(T) (= NBRC 108862(T) = KCTC15143(T)) and
      JA576(T) (= NBRC 108863(T) = KCTC 15144(T)), respectively.

PMID- 22389283
TI  - Reclassification of Koreibacter algae as a later heterotypic synonym of
      Paraoerskovia marina and emended descriptions of the genus Paraoerskovia Khan et
      al. 2009 and of Paraoerskovia marina Khan et al. 2009.
AB  - 16S rRNA gene sequences deposited for the type strains of Paraoerskovia marina
      (CTT-37(T); GenBank accession no. AB445007) and Koreibacter algae (DSW-2(T);
      FM995611) show a similarity of 100 %. Consequently, the type strains were
      subjected to a polyphasic recharacterization under direct comparison in order to
      clarify their taxonomic position. PvuII RiboPrint patterns and quantitative
      ratios of cellular fatty acids revealed strain-specific differences between P.
      marina DSM 21750(T) ( = CTT-37(T)) and K. algae DSM 22126(T) ( = DSW-2(T)). The
      percentage of DNA-DNA binding of 94 % indicated that the two type strains belong
      to the same genomospecies. Agreement in the peptidoglycan structure and polar
      lipid pattern, highly similar fatty acid profiles and MALDI-TOF mass spectra, the
      ability to produce acid from the same carbon sources, corresponding enzymic
      activities and DNA G+C contents of 70.8 +/- 0.3 mol%, in addition to the
      consistent characteristics reported in the original descriptions, support the
      view that the two strains should be affiliated to the same species. According to
      Rules 38 and 42 of the Bacteriological Code, Koreibacter algae should be
      reclassified as later heterotypic synonym of Paraoerskovia marina, and the
      descriptions of the genus Paraoerskovia Khan et al. 2009 and of Paraoerskovia
      marina Khan et al. 2009 are emended accordingly.

PMID- 22389284
TI  - Transfer of Wautersia numazuensis to the genus Cupriavidus as Cupriavidus
      numazuensis comb. nov.
AB  - Phylogenetic analysis of the 16S rRNA gene sequences of strains TE26(T) and K6
      belonging to Wautersia numazuensis Kageyama et al. 2005 showed the strains to be
      deeply intermingled among the species of the genus Cupriavidus. The comparison
      showed that strain TE26(T) was closely related to the type strains of Cupriavidus
      pinatubonensis (99.1 % 16S rRNA gene sequence similarity), C. basilensis (98.7
      %), C. necator (98.7 %) and C. gilardii (98.0 %). However, DNA-DNA hybridization
      experiments (less than 20 % relatedness) demonstrated that strain TE26(T) is
      different from these Cupriavidus species. A comparative phenotypic and
      chemotaxonomic analysis (based on fatty acid profiles) in combination with the
      16S rRNA gene sequence phylogenetic analysis and the DNA-DNA hybridization
      results supported the incorporation of Wautersia numazuensis into the genus
      Cupriavidus as Cupriavidus numazuensis comb. nov.; the type strain is TE26(T)
      (=LMG 26411(T) =DSM 15562(T) = CIP 108892(T)).

PMID- 22389285
TI  - Streptomyces endophyticus sp. nov., an endophytic actinomycete isolated from
      Artemisia annua L.
AB  - Three filamentous actinomycetes, strains YIM 65594(T), YIM 65638 and YIM 65642,
      were isolated from the surface-sterilized roots of Artemisia annua L. collected
      from Yunnan province, south-west China. These strains were found to have
      morphological and chemotaxonomic characteristics typical of the genus
      Streptomyces. The organisms formed an extensively branched substrate mycelium,
      with abundant aerial hyphae that differentiated into spores. The cell wall of the
      isolates contained ll-diaminopimelic acid and the menaquinones were MK-9(H(8))
      and MK-9(H(6)). The major fatty acids were anteiso-C(15 : 0), anteiso-C(17 : 0)
      and iso-C(16 : 0). Phylogenetic analysis of the 16S rRNA gene sequences of these
      strains revealed that the strains clustered together and were most closely
      related to Streptomyces kunmingensis NBRC 14463(T), with 98.5-98.6 % 16S rRNA
      gene sequence similarity. The results of DNA-DNA hybridization and physiological
      tests allowed the genotypic and phenotypic differentiation of strains YIM
      65594(T), YIM 65638 and YIM 65642 from related species. However, the high level
      of DNA-DNA relatedness between them showed that these three strains belong to the
      same species. Strain YIM 65594(T) (= DSM 41984(T) = CCTCC AA 209036(T)) was
      selected as the type strain to represent this novel species, for which the name
      Streptomyces endophyticus sp. nov. is proposed.

PMID- 22389286
TI  - Barrientosiimonas humi gen. nov., sp. nov., an actinobacterium of the family
      Dermacoccaceae.
AB  - Three novel actinobacteria, strains 39(T), 40 and 41, were isolated from soil
      collected from Barrientos Island in the Antarctic. The taxonomic status of these
      strains was determined using a polyphasic approach. Comparison of 16S rRNA gene
      sequences revealed that strain 39(T) represented a novel lineage within the
      family Dermacoccaceae and was most closely related to members of the genera
      Demetria (96.9 % 16S rRNA gene sequence similarity), Branchiibius (95.7 %),
      Dermacoccus (94.4-95.3 %), Calidifontibacter (94.6 %), Luteipulveratus (94.3 %),
      Yimella (94.2 %) and Kytococcus (93.1 %). Cells were irregular cocci and short
      rods. The peptidoglycan type was A4alpha with an L-Lys-L-Ser-D-Asp interpeptide
      bridge. The cell-wall sugars were galactose and glucose. The major menaquinone
      was MK-8(H(4)). The polar lipids were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol, phosphoglycolipid, two glycolipids
      and one unknown phospholipid. The acyl type of the cell-wall polysaccharide was N
      acetyl. The major cellular fatty acids were anteiso-C(17 : 0) (41.97 %), anteiso
      C(17 : 1)omega9c (32.16 %) and iso-C(16 : 0) (7.68 %). The DNA G+C content of
      strain 39(T) was 68.4 mol%. On the basis of phylogenetic and phenotypic
      differences from other genera of the family Dermacoccaceae, a novel genus and
      species, Barrientosiimonas humi gen. nov., sp. nov., is proposed; the type strain
      of the type species is 39(T) (=CGMCC 4.6864(T) = DSM 24617(T)).

PMID- 22389287
TI  - Gordonia phosphorivorans sp. nov., isolated from a wastewater bioreactor with
      phosphorus removal.
AB  - Two Gram-stain-positive, non-endospore-forming actinobacteria (Ca8(T)and Ca14)
      were isolated from a bioreactor with extensive phosphorus removal. Based on 16S
      rRNA gene sequence similarity comparisons, strains Ca8(T) and Ca14 were shown to
      belong to the genus Gordonia and were most closely related to Gordonia hirsuta
      DSM 44140(T) (98.0 % sequence similarity) and Gordonia hydrophobica DSM 44015(T)
      (97.2 %). In comparison with the sequences of the type strains of all other
      species of the genus Gordonia tested, similarities were below 97 %. The quinone
      systems of the strains were determined to consist predominantly of MK-9H(2). The
      polar lipid profile for both organisms consisted of diphosphatidylglycerol,
      phosphatidylglycerol, phospatidylethanolamine, phosphatidylinositol and
      phosphatidylinositol mannoside. Whole-organism hydrolysates contained meso
      diaminopimelic acid as the diamino acid of the peptidoglycan; mycolic acids were
      detected as well. These chemotaxonomic traits and the major fatty acids, which
      were C(16 : 1)cis-9, C(16 : 0) and C(18 : 1) and tuberculostearic acid strongly
      supported the grouping of strains Ca8(T) and Ca14 into the genus Gordonia. The
      two strains showed a DNA-DNA similarity of 96 %. DNA-DNA hybridizations of strain
      Ca8(T) with G. hirsuta DSM 44140(T) and G. hydrophobica DSM 44015(T) resulted in
      values of 26.3 and 25.0 %, respectively. These results and those of the
      physiological and biochemical tests allowed a clear phenotypic differentiation of
      strains Ca8(T) and Ca14 from the most closely related species of the genus
      Gordonia. It is concluded that strains Ca8(T) and Ca14 represent a novel species,
      for which the name Gordonia phosphorivorans sp. nov. is proposed, with the type
      strain Ca8(T) (= DSM 45630(T) = CCUG 61533(T) = CCM 7957(T) = LMG 26648(T)).

PMID- 22389288
TI  - Demequina flava sp. nov. and Demequina sediminicola sp. nov., isolated from sea
      sediment.
AB  - Two novel Gram-stain-positive bacteria, designated HR08-7(T) and HR08-43(T), were
      isolated from a sea sediment sample from Rishiri Island, Hokkaido, Japan, and
      their taxonomic positions were investigated by a polyphasic approach.
      Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that
      strains HR08-7(T) and HR08-43(T) and the members of the genus Demequina formed a
      monophyletic cluster with similarity range of 95.5-99.0 %. The peptidoglycan type
      of strains HR08-7(T) and HR08-43(T) was A4beta. The predominant menaquinone of
      both strains was demethylmenaquinone DMK-9(H(4)) and the major fatty acid was
      anteiso-C(15 : 0). The DNA G+C contents of strains HR08-7(T) and HR08-43(T) were
      64.5 and 62.4 mol%, respectively. The results of phylogenetic analysis and DNA
      DNA hybridization, along with differences of strains HR08-7(T) and HR08-43(T)
      from the recognized Demequina species in phenotypic characteristics, indicate
      that the two strains merit classification as representatives of two novel species
      of the genus Demequina, for which the names Demequina flava sp. nov. and
      Demequina sediminicola sp. nov. are proposed; the type strains are HR08-7(T) (=
      NBRC 105854(T) = DSM 24865(T)) and HR08-43(T) (= NBRC 105855(T) = DSM 24867(T)),
      respectively.

PMID- 22389289
TI  - Heck-type cross-dehydrogenative coupling reactions of indolizines at the 3
      position with electron-deficient alkenes through palladium-catalyzed C-H
      activation.

PMID- 22389291
TI  - Illness perception clusters at diagnosis predict psychological distress among
      women with breast cancer at 6 months post diagnosis.
AB  - OBJECTIVE: This study aimed to examine the extent to which illness perceptions
      and coping strategies among women diagnosed with breast cancer explain
      psychological distress at diagnosis and at 6 months post diagnosis relative to
      demographic and illness-related variables. METHODS: Women were recruited to the
      study shortly after diagnosis. A total of 90 women completed study materials
      (Illness Perception Questionnaire-Revised, the Cancer Coping Questionnaire and
      the Hospital Anxiety and Depression Scale) at time 1. The same questionnaires
      were sent approximately 6 months later to those who had consented at time 1, and
      completed questionnaires were returned by 72 women. RESULTS: Cluster analysis was
      used to identify groups of respondents who reported a similar profile of illness
      perception scores. Regression analysis demonstrated that one of these clusters
      was more likely to experience psychological distress than the other both at
      diagnosis and at 6 months post diagnosis. Illness perception cluster membership
      and positive focus type coping were the most important and consistent predictors
      of lower psychological distress at diagnosis and at 6 months post diagnosis.
      CONCLUSIONS: Illness perceptions remained relatively stable over the study
      period, and therefore we are unable to clarify whether changes in illness
      cognitions are associated with a corresponding change in psychological symptoms.
      Future research should evaluate the impact on psychological distress of
      interventions specifically designed to modify illness cognitions among women with
      breast cancer.

PMID- 22389292
TI  - An exploratory case-only analysis of gene-hazardous air pollutant interactions
      and the risk of childhood medulloblastoma.
AB  - BACKGROUND: There is evidence that exposure to chlorinated solvents may be
      associated with childhood medulloblastoma and primitive neuroectodermal tumor
      (M/PNET) risk. Animal models suggest genes related to detoxification and DNA
      repair are important in the carcinogenicity of these pollutants; however, there
      have been no human studies assessing the modifying effects of these genotypes on
      the association between chlorinated solvents and childhood M/PNET risk.
      PROCEDURE: We conducted a case-only study to evaluate census tract-level exposure
      to chlorinated solvents and the risk of childhood M/PNET in the context of
      detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas
      Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were
      selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated
      solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl
      chloride) was estimated from the US EPA's 1999 Assessment System for Population
      Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case
      only odds ratios and 95% confidence intervals (CIs). RESULTS: There were 11
      significant gene-environment interactions associated with childhood M/PNET risk.
      However, after correcting for multiple comparisons, only the interaction between
      high trichloroethylene levels and OGG1 rs293795 significantly increased the risk
      of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04). CONCLUSIONS:
      This study provides an initial assessment of the interaction between ambient
      levels of chlorinated solvents and potentially relevant genotypes on childhood
      M/PNET risk. Our results are exploratory and must be validated in animal models,
      as well as additional human studies.

PMID- 22389293
TI  - Surgical resection of solitary metastatic liver tumor arising from lung cancer: a
      case series.
AB  - Resectability of hepatic metastases which have developed from lung cancer is
      limited and only a few reports have been published. We report two cases of a
      surgical resection of liver metastases arising from lung cancer. A 77-year-old
      male underwent a lower left lobectomy to treat a primary large cell lung
      carcinoma. Eight months later, abdominal computed tomography revealed a slightly
      enhanced heterogeneous tumor measuring 50 mm in diameter in the right liver,
      segment 8. We performed a hepatic anterior sectionectomy. The pathological
      findings were similar to those of the primary carcinoma. After six months, there
      was no evidence of a recurring lesion. A 65-year-old female underwent an upper
      right lobectomy to treat a primary adenocarcinoma. Twenty months later, abdominal
      computed tomography revealed a heterogeneous tumor measuring 20 mm in diameter in
      the right liver, segment 7. We performed a hepatic posterior sectionectomy. The
      pathological findings were similar to those of the primary lung carcinoma. After
      twenty months, the patient died from an unresectable recurrent carcinoma in the
      lung and brain. No recurrence was detected in the liver. We recommend that
      surgical resection be considered for solitary metastatic liver tumors which
      develop from lung cancer.

PMID- 22389294
TI  - Systemic chemotherapy using carboplatin and 5-fluorouracil for extrahepatic
      metastasis of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: We have evaluated the effectiveness of systemic chemotherapy for
      patients with extrahepatic metastasis from hepatocellular carcinoma. METHODOLOGY:
      We examined the background, survival rates, median survival time and side effects
      of 15 cases in which systemic chemotherapy using carboplatin and 5-fluorouracil
      was done (chemotherapy group) and 59 cases in which chemotherapy was not done
      (non-chemotherapy group) out of a total of 74 cases of patients with extrahepatic
      metastasis from hepatocellular carcinoma. RESULTS: The prognoses of the 15
      chemotherapy cases and the 59 non-chemotherapy cases were as follows: 66.0%,
      33.3%, 20.0% at 6 months, 12 months, 18 months respectively for the chemotherapy
      cases and 44.0%, 18.2%, 7.1% respectively for the non-chemotherapy cases. Median
      survival periods were 10.7 months for the chemotherapy group and 5.1 months for
      the non-chemotherapy group. A significantly better prognosis of survival
      (p=0.037) was identified in the chemotherapy group and no serious side effects
      were observed. CONCLUSIONS: The present research preceded the approval of
      sorafenib. This systemic combination chemotherapy will provide an extended
      survival prognosis and is thus considered to be comparatively safe and effective
      in those patients.

PMID- 22389295
TI  - A clinical study on the treatment of severe hepatitis by a combined artificial
      liver.
AB  - BACKGROUND/AIMS: To focus on determining efficacy and safety of the combined
      artificial liver in treating severe hepatitis. METHODOLOGY: Ten patients with
      acute and chronic severe hepatitis were chosen for this study. A total of 19
      cases were treated with a combination of selective plasma absorption and
      selective plasma exchange and 1 was treated with plasma perfusion absorption.
      Clinical symptoms and physical signs were observed. In addition, the changes in
      biochemical markers, coagulation function, and aminogram before and after
      selective plasma perfusion absorption treatment were compared. RESULTS: Ten
      patients were able to tolerate the treatment; 8 patients were cured or improved
      whereas 2 worsened. Statistically significant differences (p<0.05) were observed
      in the serum levels of total bilirubin, direct bilirubin, indirect bilirubin,
      alanine transaminase, aspartate transaminase, alkaline phosphatase, total bile
      acids, albumin and globulin before and after the selective perfusion absorption
      treatment. In contrast, no statistically significant differences (p>0.05) were
      observed in the serum concentrations of potassium, sodium, creatinine and urea
      nitrogen, as well as in prothrombin time, partial thromboplastin time and
      aminogram changes. CONCLUSIONS: The new perfusion absorber can markedly improve
      hepatic function without influencing the metabolism of micro-molecules and
      coagulation factors.

PMID- 22389296
TI  - Predictive factors for prolonged intubation following liver transplantation.
AB  - BACKGROUND/AIMS: This study identified risk factors associated with prolonged
      intubation after living donor liver transplantation (LDLT). METHODOLOGY: Out of
      50 patients who underwent LDLT, clinical data were compared between those
      extubated within 4 days of LDLT (early group; n=20) and those extubated 5 days
      post-LDLT (delayed group; n=30). RESULTS: Univariate analysis associated the
      following factors with prolonged intubation: preoperative age >48 years (p=0.05),
      body mass index >22 kg/m2 (p=0.01), creatinine clearance <90 mL/min/1.73 m2
      (p=0.003), ratio between arterial oxygen tension and fractional inspired oxygen
      <=375 (p=0.02) and postoperative changes of body-weight per body surface area
      ((BW - preoperative BW)/BSA)) on postoperative day (POD) 3 (>2.0 kg/m2) (p=0.01).
      Multivariate analysis showed that creatinine clearance and (BW - preoperative
      BW)/BSA on POD 3 remained as independent predictive factors (p=0.04 and 0.04,
      respectively). CONCLUSIONS: We should aim for postoperative fluid management such
      that ((BW - preoperative BW)/BSA) <=2.0 kg/m2 on POD 3, especially in patients
      with low preoperative levels of creatinine clearance.

PMID- 22389297
TI  - FOXP3 expression in esophageal cancer cells is associated with poor prognosis in
      esophageal cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to determine FOXP3 expression in human
      esophageal cancer cells and to examine the relationship between the FOXP3
      expression levels and the prognosis of esophageal cancer in patients.
      METHODOLOGY: We evaluated FOXP3 in esophageal cancer tissue obtained from 60
      patients by immunohistochemistry. The data were analyzed by SPSS16.0 software
      with chi2 test, Kaplan-Meier survival curves, log-rank test and Cox regression
      analysis. Data was expressed as mean +/-SD. A two-tailed p-value of 0.05 was
      considered significant. RESULTS: Twenty nine (48.33%) were found to have FOXP3
      over-expression in esophageal cancer cells, while normal esophageal mucosal cells
      are negative. The FOXP3 over-expression had a significant correlation between
      tumor staging and lymph node metastasis. The FOXP3 negative group showed
      significantly better overall survival than the over-expression group (32.3% vs.
      13.8%, log-rank test, chi2=11.801, p=0.001). Cox regression analysis showed that
      T stage, N stage and FOXP3 protein expression were independent prognostic risk
      factors. The FOXP3 protein expression increased in a subset of esophageal cancers
      and the over-expression is associated with poor prognosis in patients with
      esophageal cancer. CONCLUSIONS: Our study suggests that blocking FOXP3 expression
      in cancer cells may lead to a novel therapeutic strategy for esophageal cancer.

PMID- 22389298
TI  - Hypertriglyceridemia aggravates ER stress and pathogenesis of acute pancreatitis.
AB  - BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG)
      have been implicated in acute pancreatitis (AP). METHODOLOGY: For cellular model,
      rat exocrine acinar cells were preincubated with palmitic acid (0.05 or 0.1
      mmol/L, 3 h) and stimulated with a cholecystokinin analog, CCK-8 (100 pmol/L, 30
      min). For animal model, rats fed a high-fat diet to cause HTG and AP was induced
      by injection of caerulein (20 MUg/kg). Injury to pancreatic cells was estimated
      by measuring amylase secretion, intracellular calcium concentration, apoptosis
      and histological changes. Expression of genes involved in ER stress-induced
      unfolded protein response (UPR) was monitored by RT-PCR and immunohistology.
      RESULTS: In CCK-8 stimulated rat acinar cells, preincubation with PA caused an
      increased secretion of amylase, a higher and prolonged accumulation of
      intracellular calcium and increased apoptosis. Rats on high-fat diet had
      significantly elevated serum triglyceride levels. Induction of AP led to
      increased apoptosis in pancreatic tissue on high-fat diet than controls. For
      favoring HTG, expression of UPR components, GRP78/Bip, XBP-1, GADD153/CHOP and
      caspase-12 was upregulated. CONCLUSIONS: Levels of markers of AP pathogenesis and
      components of UPR were elevated in the presence of excess fatty acids in
      pancreatic acinar cells. HTG appears to aggravate ER-stress and pathogenesis of
      AP.

PMID- 22389299
TI  - Detection of sentinel nodes in gastric cancer by indocyanine green fluorescence
      imaging.
AB  - BACKGROUND/AIMS: The sentinel nodes (SN) are the first nodes to receive lymphatic
      drainage from a primary tumor. The SN concept is useful to avoid unnecessary
      resection in gastric cancer. Indocyanine green (ICG) fluorescence imaging is a
      new method for detecting SN and we herein examined the usefulness of this
      technology. METHODOLOGY: The subjects comprised 39 cT1-2N0 gastric cancer
      patients who underwent standard surgery from 2006 to 2009. 0.8 mL ICG (1%) was
      injected into the submucosa around the tumor two days preoperatively (Preop
      group) or intraoperatively (Intraop group) by endoscopy. SN were postoperatively
      identified by fluorescence imaging and the accuracy of this method compared to
      the dye method was investigated for 76 patients treated from 2000-2004. RESULTS:
      SN was detected as fluorescence-positive nodes (FN) and the mean FN number was
      9.3+/-6.4. The specificity was 100% and all metastatic lymph nodes were detected
      as FN in three patients. The mean number of FNs was 7.2 in the preop group and
      12.5 in the postop group (p=0.032).The FN method was associated with a low false
      negative rate, same as the dye method. CONCLUSIONS: SN mapping using ICG
      fluorescence imaging has high accuracy and this compound can be injected
      preoperatively to detect SN.

PMID- 22389302
TI  - Covalent adaptable networks: reversible bond structures incorporated in polymer
      networks.

PMID- 22389301
TI  - Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian
      Society of Medical Oncology.
AB  - BACKGROUND/AIMS: The aims of this study were to report the clinical outcomes of
      adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric
      cancer. METHODOLOGY: The retrospective analysis included 637 patients with
      resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between
      2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy
      according to Schema for INT-0116. RESULTS: Of the 637 patients, the median of
      overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6
      months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3
      and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1
      4) were observed in 35% and 36.5% of patients, respectively. In univariate
      analysis, according to the Lauren classification, tumor grade, T stage, N stage,
      type of operation (total gastrectomy or subtotal) and surgery resection margin
      (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In
      multivariate analysis, T stage, N stage and surgical margins were found as
      effective factors on OS. T stage, N stage and Lauren classification were factors
      affecting RFS. CONCLUSIONS: Adjuvant chemo-radiotherapy after curative resection
      of gastric cancer was feasible, with acceptable toxicities in the Turkish
      population.

PMID- 22389307
TI  - Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell
      lymphoma of childhood.
AB  - BACKGROUND: Anaplastic large cell lymphoma (ALCL) represents approximately 15% of
      all pediatric non-Hodgkin lymphomas (NHL). It has distinct clinical features,
      including frequent involvement of extranodal sites and rare localization to the
      central nervous system (CNS). Despite varying treatment approaches the outcome of
      patients with ALCL has not significantly improved during the last two decades.
      PROCEDURE: From October 1997 to beginning of 2000, newly diagnosed ALCL patients
      were enrolled into AIEOP LNH-97 protocol for ALCL. Thereafter and until 2007,
      only CNS positive patients were included. AIEOP LNH-97 was based on the BFM-95
      schema for ALCL and included six high-dose chemotherapy courses. CNS prophylaxis
      was obtained with one intrathecal injection of chemotherapy in each course,
      whereas treatment of CNS involvement included three intrathecal injections
      without irradiation. RESULTS: Thirty-two patients were eligible for the study.
      Lymph-node disease was the most frequent localization (69% of the cases),
      followed by mediastinal (25%), CNS (22%), bone marrow (16%), and skin (13%)
      involvement. Probabilities of overall survival (OS) and of event-free survival
      (EFS) at 5 years for the whole population were 87% (SE 6%) and 68% (SE 8%),
      respectively. CONCLUSIONS: This study confirmed that short pulse chemotherapy is
      an efficacious treatment option for first line therapy of pediatric ALCL, and
      that dose intensity may have some relevance for outcome, but not in all of the
      patients. Refinement and optimization of therapy strategies for ALCL may
      originate from a combination of clinical and biological prospective studies, as
      those in the pipeline of current international collaboration.

PMID- 22389308
TI  - Laser ablation in titanium implants followed by biomimetic hydroxyapatite
      coating: Histomorphometric study in rabbits.
AB  - Titanium surface texture and chemistry modification successfully improves the
      host response and consequently the bone-to-implant contact surrounding dental
      implants. The aim of the present study was to investigate, using
      histomorphometrical-analysis, the effects of titanium surface modification by
      laser-ablation (Nd:YAG) followed by thin chemical deposition of HA. Forty-eight
      rabbits received one implant by tibiae of AS-machined (MS), laser-modified (LMS),
      or biomimetic hydroxyapatite-coated (HA) surface. Bone-to-implant contact (BIC)
      and bone area (BBT) were evaluated after 4, 8, and 12 weeks, at cortical and
      cancellous regions. Average BIC in the cortical region was higher (P < 0.001) on
      the LMS and HA implants for all periods, with no differences between LMS and HA.
      For the cancellous area, the LMS and HA implants showed higher (P < 0.01) BIC
      than MS at the initial periods. The LMS and HA showed similar values in the
      cortical region, but a tendency of higher values for HA in the cancellous region
      was observed in all periods. For the BBT, the differences were found only between
      HA and MS after 4 weeks in the cortical region (P < 0.05), and after 12 weeks in
      the cancellous area (P < 0.05). Our results showed that HA biomimetic coating
      preceded by laser treatment induced the contact osteogenesis and allowed the
      formation of a more stable bone-implant interface, even in earlier periods.

PMID- 22389310
TI  - Heterodyne detected nonlinear optical imaging in a lock-in free manner.
AB  - We report a compact, cost-effective tuned amplifier for frequency-selective
      amplification of the modulated signal in heterodyne detected nonlinear optical
      microscopy. Our method improved the signal to noise ratio by an order of
      magnitude compared to conventional lock-in detection, as demonstrated through
      stimulated Raman scattering imaging of live cells and tissues at the speed of 2
      MUsec/pixel. Application of the tuned amplifier to transient absorption
      microscopy is also demonstrated. The increased signal to noise ratio allowed epi
      detected in vivo imaging of myelin and blood in rat spinal cord with high spatial
      resolution.

PMID- 22389311
TI  - Ectopic pregnancy.

PMID- 22389312
TI  - Determining the role of mononuclear phagocytes in prion neuroinvasion from the
      skin.
AB  - Many prion diseases are acquired by peripheral exposure, and skin lesions are an
      effective route of transmission. Following exposure, early prion replication,
      upon FDCs in the draining LN is obligatory for the spread of disease to the
      brain. However, the mechanism by which prions are conveyed to the draining LN is
      uncertain. Here, transgenic mice were used, in which langerin(+) cells, including
      epidermal LCs and langerin(+) classical DCs, were specifically depleted. These
      were used in parallel with transgenic mice, in which nonepidermal CD11c(+) cells
      were specifically depleted. Our data show that prion pathogenesis, following
      exposure via skin scarification, occurred independently of LC and other
      langerin(+) cells. However, the depletion of nonepidermal CD11c(+) cells impaired
      the early accumulation of prions in the draining LN, implying a role for these
      cells in the propagation of prions from the skin. Therefore, together, these data
      suggest that the propagation of prions from the skin to the draining LN occurs
      via dermal classical DCs, independently of langerin(+) cells.

PMID- 22389313
TI  - The emerging role of microRNA in regulation of endotoxin tolerance.
AB  - Endotoxin tolerance is a phenomenon where cells show reduced responsiveness
      toward repeated endotoxin stimulation. Regulation of tolerance occurs at multiple
      levels of the cell signaling cascade, and many of these levels are potentially
      regulated by miRNA, which are a class of small RNA that bind to mRNA to down
      regulate gene expression at the post-transcriptional level. Roles have been
      identified for miR-146a, miR-221, miR-579, miR-125b, miR-155, let-7e, and miR-98
      in regulating the TLR4 signaling pathway during the development of endotoxin
      tolerance at receptor, signaling pathway, and gene transcription and
      translational levels. miRNA represent exciting, new potential targets in attempts
      to exogenously modulate development of endotoxin tolerance.

PMID- 22389314
TI  - Endothelial cell responses to micropillar substrates of varying dimensions and
      stiffness.
AB  - In the vascular niche, the extracellular matrix (ECM) provides a structural
      scaffold with a rich ligand landscape of essential matrix proteins that supports
      the organization and stabilization of endothelial cells (ECs) into functional
      blood vessels. Many of the physical interactions between ECs and macromolecular
      components of the ECM occur at both the micron and submicron scale. In addition,
      the elasticity of the ECM has been shown to be a critical factor in the progress
      of the angiogenic cascade. Here, we sought to determine the effect of substrate
      topography and elasticity (stiffness) on EC behavior. Utilizing a unique SiO(2)
      substrate with an array of micropillars, we first demonstrate that micropillars
      with heights >3 MUm significantly decrease EC adhesion and spreading. Fibronectin
      (Fn) patterning of 1 MUm high micropillars enabled EC adhesion onto the
      micropillars and promoted alignment in a single-cell chain manner. We then
      developed a robust method to generate a soft micropillar substrate array made of
      polydimethylsiloxane (PDMS), similar to the SiO(2) substrate. Finally, we
      examined the kinetics of EC adhesion and spreading on the soft PDMS substrates
      compared to the stiff SiO(2) substrates. Culturing cells on the PDMS substrates
      demonstrated an enhanced EC elongation and alignment when compared to stiff
      SiO(2) with similar topographical features. We conclude that the elongation and
      alignment of ECs is coregulated by substrate topography and stiffness and can be
      harnessed to guide vascular organization.

PMID- 22389315
TI  - P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties
      in basal-like breast cancer.
AB  - Although the luminal progenitor cell of the normal mammary gland hierarchy has
      been proposed as the cell-of-origin for basal-like breast cancers, finding the
      cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task,
      mostly due to the lack of specific markers. Recently, basal-like sporadic and
      familial cases of breast cancer have been linked to BRCA1 gene inactivation,
      which enables the upregulation of the target-repressed CDH3/P-cadherin gene, an
      important biomarker of basal-like breast carcinomas. Previously, we demonstrated
      that P-cadherin overexpression can mediate aggressive behavior in these tumors.
      Thus, our aim was to test whether P-cadherin mediates stem cell properties in
      basal-like breast carcinomas. Using a series of breast cancer cell lines and
      primary tumors, we showed that P-cadherin was directly associated with the
      expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1
      in the basal subtype. Moreover, cell population enriched for P-cadherin
      expression comprised increased in vitro mammosphere-forming efficiency and
      capacity to grow colonies in three-dimensional cultures as well as greater
      tumorigenicity. Importantly, an association was found with stem-/progenitor-like
      phenotypes of the breast, including the luminal progenitor population, CD49f(+)
      CD24(+). Additionally, P-cadherin expression conferred resistance to x-ray
      induced cell death, sustaining a role for this molecule in another stem cell
      property. In summary, we demonstrated, for the first time, that P-cadherin
      mediates stem cell properties, which could be explored in order to better define
      the CSC phenotype of basal-like breast tumors and the cell-of-origin of this
      malignancy.

PMID- 22389316
TI  - Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear
      optical microscopy.
AB  - Advances in pharmaceutical nanotechnology have yielded ever increasingly
      sophisticated nanoparticles for medicine delivery. When administered via oral,
      intravenous, ocular and transcutaneous delivery routes, these nanoparticles can
      elicit enhanced drug performance. In spite of this, little is known about the
      mechanistic processes underlying interactions between nanoparticles and tissues,
      or how these correlate with improved pharmaceutical effects. These mechanisms
      must be fully understood before nanomedicines can be rationally engineered to
      optimise their performance. Methods to directly visualise these particulates
      within tissue samples have traditionally involved imaging modalities requiring
      covalent labelling of fluorescent or radioisotope contrast agents. We present
      CARS, second harmonic generation and two photon fluorescence microscopy combined
      as a multi-modal label-free method for pinpointing polymeric nanoparticles within
      the stomach, intestine, gall bladder and liver. We demonstrate for the first time
      that orally administered chitosan nanoparticles follow a recirculation pathway
      from the GI tract via enterocytes, to the liver hepatocytes and intercellular
      spaces and then to the gall bladder, before being re-released into the gut
      together with bile.

PMID- 22389319
TI  - "Different strokes for different folks".

PMID- 22389318
TI  - Psychosocial subtypes on the behavior assessment system for children, second
      edition following pediatric traumatic brain injury.
AB  - This study identified the subtypes of psychosocial functioning in children who
      had sustained traumatic brain injury using the Behavior Assessment System for
      Children, Second Edition. Participants (N = 91) were aged 6-20. Using
      hierarchical agglomerative clustering techniques, a reliable typology emerged
      that consisted of two subtypes, which were labeled as Normal and Pervasive
      Emotional Difficulties. Using further exploratory analyses, other less
      statistically reliable subtypes were also observed, which were thought to have
      clinical significance. These were labeled as Mild Externalizing/Depression, Mild
      Externalizing/Attention Problems, Mild Depression, and Mild Anxiety. The majority
      of participants were assigned to the Normal subtype. Relationships between
      subtypes and other variables, including gender, time elapsed since injury, age at
      injury, and age at testing were also analyzed, with time elapsed since injury
      being the only variable to significantly differentiate the subtypes.

PMID- 22389320
TI  - Nanocarbon composites and hybrids in sustainability: a review.
AB  - There is an ever-growing need to protect our environment by increasing energy
      efficiency and developing "clean" energy sources. These are global challenges,
      and their resolution is vital to our energy security. Although many conventional
      materials, such as metals, ceramics, and plastics, cannot fulfil all requirements
      for these new technologies, many material combinations can offer synergistic
      effects that create improved and even new properties. The implementation of
      nanocarbons, such as graphene and carbon nanotubes, into nanocomposites and, more
      recently, into the new class of hybrids, are very promising examples. In contrast
      to classical nanocomposites, where a low volume fraction of the carbon component
      is mixed into a polymer or ceramic matrix, hybrids are materials in which
      nanocarbon is coated with a thin layer of the functional compound, which
      introduces the interface as a powerful new parameter. Based on interfacial charge
      and energy transfer processes, nanocarbon hybrids have shown increased
      sensitivities in gas sensors, improved efficiencies in photovoltaics, superior
      activities in photocatalysts, and enhanced capacities in supercapacitors. This
      review compares the characteristics and potentials of both nanocarbon composites
      and hybrids, highlights recent developments in their synthesis and discusses key
      challenges for their use in various energy applications.

PMID- 22389321
TI  - Histamine down-regulates IL-27 production in antigen-presenting cells.
AB  - Histamine is a potent mediator in allergic inflammation with immunomodulatory
      properties. Since histamine was described to inhibit IL-12 production in human
      APCs, we hypothesized that also the expression of IL-27, a newly described member
      of the IL-12 family, which is present in inflammatory skin lesions, is modulated
      by histamine. Stimulation of human monocytes with histamine resulted in
      significant reduction of TLR ligand-induced IL-27 production in human monocytes.
      IL-27 subunits, p28 and EBI3, were down-regulated at the mRNA and protein level,
      whereas other cytokines, such as IL-6, IL-10, and TNF-alpha, were not influenced.
      Studies with histamine receptor-specific agonists and antagonists showed that the
      down-regulation of IL-27 was mediated via H(2)R and H(4)R but not H(1)R and
      H(3)R. Human KCs treated with supernatants of histamine-prestimulated monocytes
      induced significantly less CXCL10 than supernatants containing high levels of IL
      27. DCs from H(4)R(-/-) mice responded to TLR simulation with higher IL-27
      production as compared with WT mice. The down-regulation of IL-27 by histamine
      might be a new mechanism in the pathogenesis of inflammatory skin diseases, in
      particular, if increased concentrations of histamine are present at sites of
      inflammation, such as in chronic eczema and psoriasis.

PMID- 22389323
TI  - Synthesis of nitrogen-rich mesoporous carbon nitride with tunable pores, band
      gaps and nitrogen content from a single aminoguanidine precursor.
AB  - Highly ordered mesoporous carbon nitride (CN) with an extremely high nitrogen
      content and tunable pore diameters was synthesized by using a new precursor with
      a high nitrogen content, aminoguanidine hydrochloride and mesoporous silica SBA
      15 with different pore diameters as hard templates. Surprisingly, the N/C ratio
      of the prepared mesoporous CN (MCN-4: 1.80) was considerably higher than that of
      the theoretically predicted C(3)N(4) nanostructures (1.33). This is mainly due to
      the fact that the CN precursor easily undergoes polymerization at high
      temperature and affords a highly stable polymer composed of a diamino-s-tetrazine
      moiety with a six-membered aromatic ring containing six nitrogen atoms that are
      linked trigonally with the nitrogen atoms. The obtained materials were thoroughly
      characterized by means of XRD, nitrogen adsorption, high resolution TEM, electron
      energy loss spectra, high resolution SEM, X-ray photoelectron spectroscopy, FTIR,
      and C, N, O, and S analysis. The results show that the MCN-4 materials possess a
      well-ordered mesoporous structure similar to SBA-15 with a high specific surface
      area and tunable band gap in the range of 2.25-2.49 eV. Interestingly, the pore
      diameter of the materials can be finely tuned from 3.1-5.8 nm by increasing the
      pore diameter of the hard-template SBA-15. The reaction temperature plays a
      critical role for the formation of MCN, and we found that 400  degrees C is the
      best condition to obtain MCN-4 with a high nitrogen content. We have further
      investigated the catalytic application of the MCN-4 materials towards Friedel
      Crafts hexanoylation of benzene and compared the results with the mesoporous CN
      with less nitrogen content (MCN-1) and nonporous CN. Among the materials studied,
      MCN-4 showed the highest activity, affording a high yield of hexanophenone within
      a few hours, which is mainly due to the presence of free amine groups on the wall
      structure of MCN-4.

PMID- 22389324
TI  - Signaling pathways of immobilized FGF-2 on silicon-substituted hydroxyapatite.
AB  - Therapeutic strategies for bone regeneration involve the selection of suitable
      biomaterials, growth factors, and cell types to mimic the cellular
      microenvironment where molecular and mechanical signals control the
      reconstruction of bone tissue. The immobilization of basic fibroblast growth
      factor (FGF-2) on powdered silicon-substituted hydroxyapatite (Si-HA) allows to
      prepare a biofunctional biomaterial able to interact with bone cells in a very
      specific way. The biological activity of FGF-2/Si-HA, evaluated in Saos-2
      osteoblasts and MC3T3-E1 preosteoblasts through the PLCgamma and MAPK/ERK signal
      transduction pathways, shows that FGF-2 immobilized on Si-HA provides the right
      signals to cells stimulating crucial intracellular mechanisms of osteoblast
      proliferation and differentiation.

PMID- 22389326
TI  - Childhood adversity and certain mental health disorders are associated with
      increased risk of incident drug use among adults.

PMID- 22389325
TI  - Niacin increases HDL biogenesis by enhancing DR4-dependent transcription of ABCA1
      and lipidation of apolipoprotein A-I in HepG2 cells.
AB  - The lipidation of apoA-I in liver greatly influences HDL biogenesis and plasma
      HDL levels by stabilizing the secreted apoA-I. Niacin is the most effective lipid
      regulating agent clinically available to raise HDL. This study was undertaken to
      identify regulatory mechanisms of niacin action in hepatic lipidation of apoA-I,
      a critical event involved in HDL biogenesis. In cultured human hepatocytes
      (HepG2), niacin increased: association of apoA-I with phospholipids and
      cholesterol by 46% and 23% respectively, formation of lipid-poor single apoA-I
      molecule-containing particles up to ~2.4-fold, and pre beta 1 and alpha migrating
      HDL particles. Niacin dose-dependently stimulated the cell efflux of phospholipid
      and cholesterol and increased transcription of ABCA1 gene and ABCA1 protein.
      Mutated DR4, a binding site for nuclear factor liver X receptor alpha (LXR alpha
      ) in the ABCA1 promoter, abolished niacin stimulatory effect. Further, knocking
      down LXR alpha or ABCA1 by RNA interference eliminated niacin-stimulated apoA-I
      lipidation. Niacin treatment did not change apoA-I gene expression. The present
      data indicate that niacin increases apoA-I lipidation by enhancing lipid efflux
      through a DR4-dependent transcription of ABCA1 gene in HepG2 cells. A stimulatory
      role of niacin in early hepatic formation of HDL particles suggests a new
      mechanism that contributes to niacin action to increase the stability of newly
      synthesized circulating HDL.

PMID- 22389327
TI  - Depression 3 and 9 months after discharge is less common in cardiac patients who
      are receiving statins at discharge.

PMID- 22389328
TI  - Review: limited evidence from two small trials suggests no improvement in ASD
      symptoms with short term omega-3 supplementation.

PMID- 22389329
TI  - Carbon-based electrochemical capacitors.
AB  - Supercapacitors are one of the key devices for energy-storage applications. They
      have energy densities much higher than those of conventional capacitors and
      possess much better power delivery capabilities than batteries. This makes them
      unique devices that can outperform both batteries and conventional capacitors
      under special circumstances. Nanocarbons are the main electrode materials for
      supercapacitors. Abundant sources of nanocarbons and facile processes of
      modification have led to the fabrication of cheap electrodes. In this review, we
      focus on the capacitance performance of highly porous activated carbons and
      attempt to determine the role of different pores. Elaborate discussions are
      presented on individual contributions from micro- and mesopores and their mutual
      dependence. This article also presents a comparative performance report for both
      random and ordered porous nanocarbons. Novel carbon materials, such as carbon
      nanotubes and graphene, and their contributions in this context are discussed. We
      summarize key techniques for the functionalization of nanocarbons and their
      pseudocapacitive charge-storage mechanisms. Nanocarbon composites with redox
      active transition-metal oxides and conducting polymers are highlighted along with
      their impact as electrode materials. Ideal composite structures are highlighted
      and an attempt is made to determine an ideal future electrode structure for
      capacitors with high energy and power density.

PMID- 22389330
TI  - Metal-free nitrogen-containing carbon nanotubes prepared from triazole and
      tetrazole derivatives show high electrocatalytic activity towards the oxygen
      reduction reaction in alkaline media.
AB  - High-performance oxygen reduction reaction (ORR) catalysts based on metal-free
      nitrogen-containing precursors and carbon nanotubes are reported. The
      investigated systems allow the evaluation of the effect of nitrogen-containing
      groups towards ORR and the results show that the catalysts are compatible with
      the conditions encountered in alkaline fuel cells, exhibiting good catalytic
      activity and stability compared with conventional Pt/C electrocatalyst.

PMID- 22389332
TI  - Cost effectiveness of interventions to tackle non-communicable diseases.

PMID- 22389331
TI  - Quantifying apoprotein synthesis in rodents: coupling LC-MS/MS analyses with the
      administration of labeled water.
AB  - Stable isotope tracer studies of apoprotein flux in rodent models present
      difficulties as they require working with small volumes of plasma. We demonstrate
      the ability to measure apoprotein flux by administering either (2)H- or (18)O
      labeled water to mice and then subjecting samples to LC-MS/MS analyses; we were
      able to simultaneously determine the labeling of several proteolytic peptides
      representing multiple apoproteins. Consistent with relative differences reported
      in the literature regarding apoprotein flux in humans, we found that the
      fractional synthetic rate of apoB is greater than apoA1 in mice. In addition, the
      method is suitable for quantifying acute changes in protein flux: we observed a
      stimulation of apoB production in mice following an intravenous injection of
      Intralipid and a decrease in apoB production in mice treated with an inhibitor of
      microsomal triglyceride transfer protein. In summary, we demonstrate a high
      throughput method for studying apoprotein kinetics in rodent models. Although
      notable differences exist between lipoprotein profiles that are observed in
      rodents and humans, we expect that the method reported here has merit in studies
      of dyslipidemia as i) rodent models can be used to probe target engagement in
      cases where one aims to modulate apoprotein production and ii) the approach
      should be adaptable to studies in humans.

PMID- 22389333
TI  - Commission proposes new rules for deciding doctors' fitness to practise.

PMID- 22389334
TI  - GPs' leader calls for new dialogue on NHS if health bill is scrapped.

PMID- 22389335
TI  - Intervention strategies to reduce the burden of non-communicable diseases in
      Mexico: cost effectiveness analysis.
AB  - OBJECTIVE: To inform decision making regarding intervention strategies against
      non-communicable diseases in Mexico, in the context of health reform. DESIGN:
      Cost effectiveness analysis based on epidemiological modelling. INTERVENTIONS:
      101 intervention strategies relating to nine major clusters of non-communicable
      disease: depression, heavy alcohol use, tobacco use, cataracts, breast cancer,
      cervical cancer, chronic obstructive pulmonary disease, cardiovascular disease,
      and diabetes. DATA SOURCES: Mexican data sources were used for most key input
      parameters, including administrative registries; disease burden and population
      estimates; household surveys; and drug price databases. These sources were
      supplemented as needed with estimates for Mexico from the WHO-CHOICE unit cost
      database or with estimates extrapolated from the published literature. MAIN
      OUTCOME MEASURES: Population health outcomes, measured in disability adjusted
      life years (DALYs); costs in 2005 international dollars ($Int); and costs per
      DALY. RESULTS: Across 101 intervention strategies examined in this study, average
      yearly costs at the population level would range from around <=$Int1m (such as
      for cataract surgeries) to >$Int1bn for certain strategies for primary prevention
      in cardiovascular disease. Wide variation also appeared in total population
      health benefits, from <1000 DALYs averted a year (for some components of cancer
      treatments or aspirin for acute ischaemic stroke) to >300,000 averted DALYs (for
      aggressive combinations of interventions to deal with alcohol use or
      cardiovascular risks). Interventions in this study spanned a wide range of
      average cost effectiveness ratios, differing by more than three orders of
      magnitude between the lowest and highest ratios. Overall, community and public
      health interventions such as non-personal interventions for alcohol use, tobacco
      use, and cardiovascular risks tended to have lower cost effectiveness ratios than
      many clinical interventions (of varying complexity). Even within the community
      and public health interventions, however, there was a 200-fold difference between
      the most and least cost effective strategies examined. Likewise, several clinical
      interventions appeared among the strategies with the lowest average cost
      effectiveness ratios-for example, cataract surgeries. CONCLUSIONS: Wide
      variations in costs and effects exist within and across intervention categories.
      For every major disease area examined, at least some strategies provided
      excellent value for money, including both population based and personal
      interventions.

PMID- 22389336
TI  - What are the priorities for prevention and control of non-communicable diseases
      and injuries in sub-Saharan Africa and South East Asia?

PMID- 22389337
TI  - Cost effectiveness of strategies to combat cardiovascular disease, diabetes, and
      tobacco use in sub-Saharan Africa and South East Asia: mathematical modelling
      study.
AB  - OBJECTIVE: To determine the relative costs and health effects of interventions to
      combat cardiovascular disease, diabetes, and tobacco related disease in order to
      guide the allocation of resources in developing countries. DESIGN: Cost
      effectiveness analysis of 123 single or combined prevention and treatment
      strategies for cardiovascular disease, diabetes, and smoking by means of a
      lifetime population model. SETTING: Two World Health Organization sub-regions of
      the world: countries in sub-Saharan Africa with very high adult and high child
      mortality (AfrE) and countries in South East Asia with high adult and high child
      mortality (SearD). DATA SOURCES: Demographic and epidemiological data were taken
      from the WHO databases of mortality and global burden of disease. Estimates of
      intervention coverage, effectiveness, and resource needs were drawn from clinical
      trials, observational studies, and treatment guidelines. Unit costs were taken
      from the WHO-CHOICE (Choosing Interventions that are Cost-Effective) price
      database. MAIN OUTCOME MEASURES: Cost per disability adjusted life year (DALY)
      averted, expressed in international dollars ($Int) for the year 2005. RESULTS:
      Most of the interventions studied were considered highly cost effective, meaning
      they generate one healthy year of life at a cost of <$Int2000 (which is the gross
      domestic product per capita of the two regions considered here). Interventions
      that offer particularly good monetary value, and which could be considered for
      prioritised implementation or scale up, include demand reduction strategies of
      the Framework Convention for Tobacco Control (<$Int950 and <$Int200 per DALY
      averted in AfrE and SearD respectively); combination drug therapy for people with
      a >25% chance of experiencing a cardiovascular event over the next decade, either
      alone or together with specific multidrug regimens for the secondary prevention
      of post-acute ischaemic heart disease and stroke (<$Int150 and <$Int230 per DALY
      averted in AfrE and SearD respectively); and retinopathy screening and glycaemic
      control for patients with diabetes (<$Int2100 and <$Int950 per DALY averted in
      AfrE and SearD respectively). CONCLUSION: This comparative economic assessment
      has identified a set of population-wide and individual strategies for prevention
      and control of cardiovascular disease that are inexpensive and cost effective in
      low resource settings.

PMID- 22389338
TI  - Cost effectiveness of strategies to combat chronic obstructive pulmonary disease
      and asthma in sub-Saharan Africa and South East Asia: mathematical modelling
      study.
AB  - OBJECTIVES: To determine the population level costs, effects, and cost
      effectiveness of selected, individual based interventions to combat chronic
      obstructive pulmonary disease (COPD) and asthma in the context of low and middle
      income countries. DESIGN: Sectoral cost effectiveness analysis using a lifetime
      population model. SETTING: Two World Health Organization sub-regions of the
      world: countries in sub-Saharan Africa with very high adult and high child
      mortality (AfrE); and countries in South East Asia with high adult and high child
      mortality (SearD). DATA SOURCES: Disease rates and profiles were taken from the
      WHO Global Burden of Disease study; estimates of intervention effects and
      resource needs were drawn from clinical trials, observational studies, and
      treatment guidelines. Unit costs were taken from a WHO price database. MAIN
      OUTCOME MEASURES: Cost per disability adjusted life year (DALY) averted,
      expressed in international dollars ($Int) for the year 2005. RESULTS: In both
      regions low dose inhaled corticosteroids for mild persistent asthma was
      considered the most cost effective intervention, with average cost per DALY
      averted about $Int2500. The next best value strategies were influenza vaccine for
      COPD in Sear-D (incremental cost $Int4950 per DALY averted) and low dose inhaled
      corticosteroids plus long acting beta agonists for moderate persistent asthma in
      Afr-E (incremental cost $Int9112 per DALY averted). CONCLUSIONS: COPD is
      irreversible and progressive, and current treatment options produce relatively
      little gains relative to the cost. The treatment options available for asthma,
      however, generally decrease chronic respiratory disease burden at a relatively
      low cost.

PMID- 22389339
TI  - Cost effectiveness of strategies to combat neuropsychiatric conditions in sub
      Saharan Africa and South East Asia: mathematical modelling study.
AB  - OBJECTIVE: To assess the comparative costs and effects of interventions to combat
      five neuropsychiatric conditions (schizophrenia, bipolar disorder, depression,
      epilepsy, and heavy alcohol use). DESIGN: Cost effectiveness analysis based on an
      epidemiological model. SETTING: Two epidemiologically defined World Health
      Organization sub-regions of the world: countries in sub-Saharan Africa with very
      high adult and high child mortality (AfrE); and countries in South East Asia with
      high adult and high child mortality (SearD). DATA SOURCES: Published studies,
      costing databases. MAIN OUTCOME MEASURES: Cost per capita and cost per disability
      adjusted life year (DALY) averted, expressed in international dollars ($Int) for
      the year 2005. RESULTS: Across 44 assessed intervention strategies for the five
      neuropsychiatric conditions, cost effectiveness values differed by as much as two
      orders of magnitude (from $Int100-250 to $Int10,000-25,000 for a year of healthy
      life gained). In both sub-regions, inpatient based treatment of schizophrenia
      with newer antipsychotic drugs was the most costly and least cost effective
      strategy. The most cost effective strategies in the African sub-region related to
      population based alcohol control, while in the South East Asian sub-region the
      most cost effective intervention was drug treatment of epilepsy in primary care.
      The cumulative cost per capita of the most cost effective set of interventions
      covering all five conditions was estimated at $Int4.90-5.70. This package
      comprises interventions for epilepsy (older first line antiepileptic drugs);
      depression (generically produced newer antidepressants and psychosocial
      treatment); bipolar disorder (mood stabiliser drug lithium); schizophrenia
      (neuroleptic antipsychotic drugs and psychosocial treatment); and heavy alcohol
      use (increased taxation and its enforcement, reduced access, and, in the African
      sub-region, advertising bans and brief advice to heavy drinkers in primary care).
      CONCLUSIONS: Reallocation of resources to cost effective intervention strategies
      would increase health gain, save money and help implement much needed expansion
      of services for neuropsychiatric conditions in low resource settings.

PMID- 22389340
TI  - Cost effectiveness of strategies to combat road traffic injuries in sub-Saharan
      Africa and South East Asia: mathematical modelling study.
AB  - OBJECTIVE: To identify and estimate the population costs and effects of a
      selected set of enforcement strategies for reducing the burden of road traffic
      injuries in developing countries. DESIGN: Cost effectiveness analysis based on an
      epidemiological model. SETTING: Two epidemiologically defined World Health
      Organization sub-regions of the world: countries in sub-Saharan Africa with very
      high adult and high child mortality (AfrE); and countries in South East Asia with
      high adult and high child mortality (SearD). INTERVENTIONS: Enforcement of speed
      limits via mobile speed cameras; drink-drive legislation and enforcement via
      breath testing campaigns; legislation and primary enforcement of seatbelt use in
      cars; legislation and enforcement of helmet use by motorcyclists; legislation and
      enforcement of helmet use by bicyclists. MAIN OUTCOME MEASURES: Patterns of
      injury were fitted to a state transition model to determine the expected
      population level effects of intervention over a 10 year period, which were
      expressed in disability adjusted life years (DALYs) averted. Costs were expressed
      in international dollars ($Int) for the year 2005. RESULTS: The single most cost
      effective strategy varies by sub-region, but a combined intervention strategy
      that simultaneously enforces multiple road safety laws produces the most health
      gain for a given amount of investment. For example, the combined enforcement of
      speed limits, drink-driving laws, and motorcycle helmet use saves one DALY for a
      cost of $Int1000-3000 in the two sub-regions considered. CONCLUSIONS: The
      potential impact of available road safety measures is inextricably bound by the
      underlying distribution of road traffic injuries across different road user
      groups and risk factors. Combined enforcement strategies are expected to
      represent the most efficient way to reduce the burden of road traffic injuries,
      because they benefit from considerable synergies on the cost side while
      generating greater overall health gains.

PMID- 22389341
TI  - Cost effectiveness of strategies to combat vision and hearing loss in sub-Saharan
      Africa and South East Asia: mathematical modelling study.
AB  - OBJECTIVE: To determine the relative costs, effects, and cost effectiveness of
      selected interventions to control cataract, trachoma, refractive error, hearing
      loss, meningitis and chronic otitis media. DESIGN: Cost effectiveness analysis of
      or combined strategies for controlling vision and hearing loss by means of a
      lifetime population model. SETTING: Two World Health Organization sub-regions of
      the world where vision and hearing loss are major burdens: sub-Saharan Africa and
      South East Asia. DATA SOURCES: Biological and behavioural parameters from
      clinical and observational studies and population based surveys. Intervention
      effects and resource inputs based on published reports, expert opinion, and the
      WHO-CHOICE database. MAIN OUTCOME MEASURES: Cost per disability adjusted life
      year (DALY) averted, expressed in international dollars ($Int) for the year 2005.
      RESULTS: Treatment of chronic otitis media, extracapsular cataract surgery,
      trichiasis surgery, treatment for meningitis, and annual screening of
      schoolchildren for refractive error are among the most cost effective
      interventions to control hearing and vision impairment, with the cost per DALY
      averted <$Int285 in both regions. Screening of both schoolchildren (annually) and
      adults (every five years) for hearing loss costs around $Int1000 per DALY
      averted. These interventions can be considered highly cost effective. Mass
      treatment with azithromycin to control trachoma can be considered cost effective
      in the African but not the South East Asian sub-region. CONCLUSIONS: Vision and
      hearing impairment control interventions are generally cost effective. To decide
      whether substantial investments in these interventions is warranted, this finding
      should be considered in relation to the economic attractiveness of other,
      existing or new, interventions in health.

PMID- 22389342
TI  - Pulmonary sequestration after resection of contralateral congenital pulmonary
      sequestration.

PMID- 22389343
TI  - Lung volume reduction surgery for native lung hyperinflation following single
      lung transplantation for emphysema: which patients?
AB  - OBJECTIVES: Lung transplantation is an established treatment for patients with
      advanced emphysema. Double-lung transplantation is favoured to avoid
      complications following single-lung transplantation, including native lung
      hyperinflation. Nonetheless, single-lung transplantation continues due to limited
      donor organ availability. The aim of this study was to evaluate the pre-operative
      assessment, surgical techniques and outcomes in patients undergoing lung volume
      reduction surgery for native lung hyperinflation. METHODS: Eight patients
      underwent lung volume reduction surgery for native lung hyperinflation between
      October 2008 and April 2011. Symptoms, pre-operative evaluation, peri-operative
      morbidity, length of stay, pulmonary function and survival were examined. The
      mean follow-up was 17 months. RESULTS: Participants underwent high resolution CT
      and bronchoscopy with transbronchial biopsy and bronchial washings to exclude
      alternative causes for deterioration in pulmonary function tests. V/Q scan was
      performed to assess the contribution of each lung to overall function.
      Measurement of inspiratory airflow resistance in each lung was performed in one
      case. Seven patients underwent multiple wedge resections and one underwent
      bilobectomy. All patients survived to hospital discharge, and mean length of stay
      was 13.9 days. Functional improvement was demonstrated in all cases at follow-up,
      with a mean percentage increase of 29.3% in forced expiratory volume in one
      second and 21.6% in forced vital capacity. Symptomatic improvement was also
      reported by all patients post-operatively. CONCLUSIONS: Lung volume reduction
      surgery for native lung hyperinflation is an effective treatment strategy with an
      acceptable level of surgical risk. Patient selection, however, remains vital. The
      non-anatomical multiple wedge excision technique used here was as effective as
      anatomical lung volume reduction surgery used in other series. With regard to pre
      operative assessment, the measurement of single-lung inspiratory airflow
      resistance is of particular interest. We feel that this may provide an additional
      method of differentiating between native lung hyperinflation and obliterative
      bronchiolitis prior to surgery, thus improving patient selection.

PMID- 22389344
TI  - Analysis of risk factors for neurological dysfunction in patients with acute
      aortic dissection type A: data from the German Registry for Acute Aortic
      Dissection type A (GERAADA).
AB  - OBJECTIVES: Acute aortic dissection type A (AADA) is associated with major
      adverse events, such as transient or persistent neurological dysfunction (ND),
      which may be patient-, disease- or surgery-related. There is a lack of consensus
      regarding risk factors for ND in AADA patients. The aim of this study was to
      analyse and identify risk factors for new postoperative ND after aortic repair
      for AADA. METHODS: Between July 2006 and June 2010, 2137 AADA patients were
      enrolled in the multi-centre, prospective German Registry of AADA (GERAADA).
      Perioperative data were prospectively gathered from 50 institutes in Austria,
      Switzerland and Germany, and multivariate logistic regression analysis was
      performed to determine the independent predictors of new onset ND. RESULTS: ND
      occurred in 20.3% of all patients prior to surgery, 12.6% of which resolved
      postoperatively and 7.7% persisted. New ND after AADA surgery occurred in 9.5% of
      patients. Risk factors for an increased rate of postoperative new ND were
      malperfusion syndrome of three or more territories prior to surgery [odds ratio
      (OR) = 2.206, P = 0.0065], dissection of the supraaortic vessels (OR = 1.468, P =
      0.0103) and longer operating time (OR = 1.002 per min, P = 0.0001). New
      postoperative ND was associated with an increased rate of mortality (22.5 vs.
      16.1%, P = 0.0087). Arterial cannulation site had no statistically significant
      impact on neurological outcomes. CONCLUSIONS: Neurological complications are
      associated with increased mortality post-AADA repair. New onset ND is associated
      with extensive malperfusion syndrome, supraaortic vessel dissection and operative
      time and does not seem to be affected by choice of arterial cannulation site.

PMID- 22389345
TI  - Government makes U turn over legal aid for some clinical negligence claims.

PMID- 22389346
TI  - New scheme aims to eradicate congenital syphilis in three years.

PMID- 22389348
TI  - Regional networks for children suffering major trauma.

PMID- 22389347
TI  - Cost effectiveness of strategies to combat breast, cervical, and colorectal
      cancer in sub-Saharan Africa and South East Asia: mathematical modelling study.
AB  - OBJECTIVE: To determine the costs and health effects of interventions to combat
      breast, cervical, and colorectal cancers in order to guide resource allocation
      decisions in developing countries. SETTING: Two World Health Organization sub
      regions of the world: countries in sub-Saharan Africa with very high adult and
      high child mortality (AfrE); and countries in South East Asia with high adult and
      high child mortality (SearD). DESIGN: Cost effectiveness analysis of prevention
      and treatment strategies for breast, cervical, and colorectal cancer, using
      mathematical modelling based on a lifetime population model. DATA SOURCES:
      Demographic and epidemiological data were taken from the WHO mortality and global
      burden of disease databases. Estimates of intervention coverage, effectiveness,
      and resource needs were based on clinical trials, treatment guidelines, and
      expert opinion. Unit costs were taken from the WHO-CHOICE price database. MAIN
      OUTCOME MEASURES: Cost per disability adjusted life year (DALY) averted,
      expressed in international dollars ($Int) for the year 2005. RESULTS: In both
      regions certain interventions in cervical cancer control (screening through
      cervical smear tests or visual inspection with acetic acid in combination with
      treatment) and colorectal cancer control (increasing the coverage of treatment
      interventions) cost <$Int2000 per DALY averted and can be considered highly cost
      effective. In the sub-Saharan African region screening for colorectal cancer (by
      colonoscopy at age 50 in combination with treatment) costs $Int2000-6000 per DALY
      averted and can be considered cost effective. In both regions certain
      interventions in breast cancer control (treatment of all cancer stages in
      combination with mammography screening) cost $Int2000-6000 per DALY averted and
      can also be considered cost effective. Other interventions, such as campaigns to
      eat more fruit and vegetable or subsidies in colorectal cancer control, are not
      cost effective according to the criteria defined. CONCLUSION: Highly cost
      effective interventions to combat cervical and colorectal cancer are available in
      the African and Asian sub-regions. In cervical cancer control, these include
      screening through smear tests or visual inspection in combination with treatment.
      In colorectal cancer, increasing treatment coverage is highly cost effective
      (screening through colonoscopy is cost effective in the African sub-region). In
      breast cancer control, mammography screening in combination with treatment of all
      stages is cost effective.

PMID- 22389349
TI  - 'Do you know where your cyanide kit is?': a study of perceived and actual
      antidote availability to emergency departments in the South West of England.
AB  - OBJECTIVE: The authors set out to investigate perceived and actual availability
      of antidotes recommended for stocking in emergency departments (EDs) by the
      College of Emergency Medicine in EDs in the South West of England. METHODS: Data
      collectors were asked to physically locate each relevant antidote in the ED, and
      check whether the recommended quantity was available. If the antidote was not
      available in the department, the data collector located where in the hospital
      stocks were available. Senior medical and nursing staff were asked to specify
      where they believed the antidotes were stored or who they would ask if they did
      not know. It was then ascertained whether their source of advice would have known
      the location. RESULTS: 5 out of 6 departments returned data with an overall
      response rate from senior medical and nursing staff of 80%. Knowledge of common
      antidote locations was variable, and stocking of antidotes did not universally
      meet the College of Emergency Medicine recommendations. CONCLUSION: Stocking of
      important antidotes should be rationalised and simplified using central
      locations, preferably close to the ED. Clinically important antidotes may not be
      available for patients when they need them. Clear guidance should be available
      for staff detailing the location of antidotes. There is a need for clarification
      around the treatment of cyanide poisoning to facilitate rational antidote
      stocking for this potentially lethal condition.

PMID- 22389350
TI  - Paediatric back pain and a limp.

PMID- 22389351
TI  - Implementation of an evidence based guideline reduces blood tests and length of
      stay for the limping child in a paediatric emergency department.
AB  - INTRODUCTION: Acute non-traumatic limp is a common reason for children to present
      to the emergency department (ED). There is a wide differential diagnosis for
      these patients, and there are certain serious conditions which cannot be missed.
      An evidence based guideline for the 'limping child' was designed and the impact
      of guideline implementation on a number of specific, predefined quantitative
      outcomes was assessed. METHODS: An initial retrospective chart review over 3
      months was carried out for all patients presenting with acute non-traumatic limp.
      Following guideline introduction and implementation, information was gathered
      prospectively for a further 3 month period. Data outcomes between the two patient
      groups were then compared. RESULTS: 110 patients met the criteria for inclusion:
      56 pre-guideline and 54 post-guideline implementation. Baseline characteristics
      and diagnosis breakdown were similar in both groups. The rate of laboratory
      investigations was significantly reduced following guideline implementation (68%
      of patients pre-guideline, vs 48% post-guideline; (chi(2)), p=0.03). The number
      of x-rays carried out was similar in each group (74 pre- vs 67 post-guideline,
      mean 1.32 vs 1.28; (chi(2)), p=0.53). Length of time spent in the ED was
      significantly reduced following guideline implementation (median time 150 min pre
      vs 82.5 min post-guideline; (chi(2)), p=0.04). No cases of serious pathology
      were missed using the guideline. CONCLUSION: Implementation of an evidence based
      clinical practice guideline for the limping child in a paediatric ED reduced the
      overall time patients spent in the ED, reduced the need for unnecessary
      laboratory investigations and ensured that appropriate investigations were
      carried out on an individual patient basis.

PMID- 22389352
TI  - Catatonia in the emergency department.
AB  - Disturbances of the level of awareness are a frequent motive of attendance to
      emergency departments where the initial assessment and management will determine
      the direction of their outcome. The syndrome of catatonia must be taken into
      consideration and although it is normally associated with psychiatric diagnoses,
      it is also very often found in a great variety of neurological and medical
      conditions. Due to the clinical complexity of catatonia, there are still
      difficulties in its correct identification and initial management, something that
      leads to diagnostic delays and increased morbidity and mortality. In this
      article, a review of the literature on catatonia is presented with the aim of
      assisting emergency department doctors (and clinicians assessing patients in
      emergency situations) in considering this condition in the differential diagnosis
      of stupor due to its high frequency of association with organic pathology.

PMID- 22389353
TI  - Evaluating acute medical admissions through emergency departments in Hong Kong:
      can one adjust for case-mix variation?
AB  - BACKGROUND: Healthcare systems are under pressure to efficiently and safely
      reduce acute care admissions to hospital. There is a need to develop a
      standardised system for assessing emergency department performance which takes
      into account case-mix variation. The objective of this study was to derive and
      validate a standardised tool for assessing variations in medical admissions
      through emergency departments in Hong Kong. METHODS: Retrospective study of
      patients attending emergency departments of 14 acute hospitals in Hong Kong. Data
      were retrieved from a centralised administrative database. RESULTS: Of 2,531,225
      patients who attended emergency departments between 1 January 2001 and 31
      December 2003, 780,444 (30.8%) were admitted to medical wards. A model derived
      from 2001 data shows well-calibrated admission probabilities, with an area under
      the receiver operating characteristic curve for probability of admission of 90.3
      (95% CI +/-0.11). The areas under the receiver operating characteristic curves
      for 2002 and 2003 validation sets were 89.9 (95% CI +/-0.11) and 89.0 (95% CI +/
      0.12), respectively. With an averaged benchmark, reductions in medical admissions
      of up to 19% could be achieved, while under the most optimistic assumption,
      reductions of up 36% could be achieved. CONCLUSIONS: A tool for benchmarking
      hospital medical admissions and minimising case-mix variation has been derived
      and validated in Hong Kong, but it requires further validation in other
      healthcare systems given the wide variations in admission thresholds
      internationally. This may be used as one potential method to evaluate the
      performance of emergency departments against a common standard.

PMID- 22389354
TI  - Survey of the use of therapeutic hypothermia after cardiac arrest in UK
      paediatric emergency departments.
AB  - OBJECTIVES: To ascertain current use of therapeutic hypothermia (TH) after
      paediatric cardiac arrest in UK emergency departments (EDs), and views on
      participating in a UK randomised controlled trial (RCT) incorporating early
      induction of TH in ED. DESIGN: Anonymous web-based survey of 77 UK Emergency
      Medicine (EM) consultants from 28 UK EDs that see children during the period
      April-June 2010. RESULTS: 62% (48/77) of surveyed consultants responded from
      21/28 (75%) EDs. All managed children post cardiac arrest. 90% (43/48) were aware
      of the literature concerning TH after cardiac arrest in adults. However, 63%
      (30/48) had never used TH in paediatric practice. All departments had at least
      one method of inducing TH (surface cooling; air/water blankets; intravenous cold
      fluid or catheters). Reasons stated for not inducing TH included no equipment
      available (26%; 11/42), TH not advocated by the local PICU (24%; 10/42) and not
      enough evidence for its use (24%; 10/42). TH was considered based on advice from
      the local Paediatric Intensive Care Units (68%; 17/25) or likelihood of recovery
      after arrest (32%; 8/25). There was strong support for a UK RCT of TH versus
      normothermia (85%; 40/47). The proposed RCT was felt to be ethical (87%; 40/48)
      with use of deferred consent acceptable (74%; 34/46). CONCLUSION: UK EM
      consultants are aware of TH but infrequently initiate the therapy in children for
      a number of reasons. Their involvement would enable early induction of TH in EDs
      after paediatric cardiac arrest during a UK RCT. The authors have demonstrated
      the availability of suitable equipment and EM consultant support for
      participation in such a RCT.

PMID- 22389355
TI  - Use of the human dive reflex for the management of supraventricular tachycardia:
      a review of the literature.
AB  - BACKGROUND: The human dive reflex (HDR), a physiological phenomenon similar to
      the bradycardia reflex used by marine mammals during prolonged submersion, can be
      employed in managing paroxysmal supraventricular tachycardia (PSVT). This review
      aims to identify a standardised HDR technique for haemodynamically stable PSVT,
      to determine the effectiveness of the HDR and to define its usefulness in the
      prehospital setting. METHODS: A review of the Medline, EMBASE and CINAHL
      databases was conducted. Articles were included if they described the use of the
      HDR to revert PSVT in the prehospital or emergency medical setting, the nature of
      the effectiveness of the HDR for PSVT or historically significant developments of
      HDR techniques for PSVT reversion. Articles not available in English or
      describing the use of HDR in animal studies only were excluded. RESULTS: 211
      articles were identified, of which 21 were found to be relevant. These included
      10 studies of HDR effectiveness in PSVT and three physiological studies of HDR
      effect. No standardised model of performance exists for the HDR. Elements of
      performance include: a cold stimulus applied to the entire face, a specific
      temperature of the cold stimulus, application duration, breath holding during HDR
      and posture assumed to perform the procedure. There are also safety and logistics
      issues with using the HDR in prehospital care. CONCLUSIONS: The HDR represents an
      effective method of terminating PSVT in the hospital emergency department. Its
      usefulness in prehospital care requires further evaluation of the elements of the
      manoeuvre to determine appropriateness to this setting.

PMID- 22389356
TI  - Tibetan plateau earthquake: altitude challenges to medical rescue work.
AB  - BACKGROUND: Rescue efforts for earthquakes in remote plateau regions require
      large numbers of professional personnel to be transported from various lowland
      regions for relief work. Unacclimatised rescuers to high-altitude regions
      commonly suffer acute mountain sickness (AMS), which makes relief efforts
      inefficient and potentially dangerous. METHODS: In this study, the AMS symptoms
      of 78 unacclimatised rescue workers for the Yushu earthquake from Beijing were
      recorded using the Lake Louise AMS self-report questionnaire. Heart rate and
      blood oxygen were recorded at rest before departure, during rest and during
      activity. RESULTS: After ascending, resting heart rate increased from mean 75.87
      bpm to 87.45 bpm and resting SpO(2) decreased from an average of 98.51% to 90.35%
      (both p<0.001). The mean Lake Louise AMS Score for participants was 3.1 (95% CI
      2.6 to 3.6). 29 members (37.2%) met the diagnosis criteria for AMS. 16 members
      (20.5%) were evacuated early due to acute AMS (AMS score >=5). Rhodiola was
      offered on a voluntary basis as a prophylactic measure but shown to be
      ineffective. CONCLUSION: Given the ineffectiveness of prophylactic measures and
      the urgency of such disaster situations, it is unrealistic to mobilise rescue
      teams from lowland regions for immediate relief efforts. A local disaster plan
      specific to plateau earthquakes needs to be developed with local personnel for
      timely and efficient relief.

PMID- 22389357
TI  - Family-based behavioural intervention programme for obese children: a feasibility
      study.
AB  - OBJECTIVES: To assess a 2-year family-based behavioural intervention programme
      against child obesity. DESIGN: Single-group pre- and post-intervention
      feasibility study. SETTING: Swedish paediatric outpatient care. PARTICIPANTS: 26
      obese children aged 8.3-12.0 years and their parents who had consented to
      actively participate in a 2-year intervention. INTERVENTIONS: 25 paediatric
      outpatient group sessions over a 2-year period with parallel groups for children
      and parents. The basis for the programme was a manual containing instructions for
      tutor-supervised group sessions with obese children and their parents. PRIMARY
      AND SECONDARY OUTCOME MEASURES: The primary outcome measure was change in
      standardised body mass index between baseline and after 36 months. The secondary
      outcome measures were change in the waist:height ratio, metabolic parameters and
      programme adherence. The participants were examined at baseline and after 3, 12
      and 24 months of therapy and at follow-up 12 months after completion of the
      programme. RESULTS: The primary outcome measure, standardised body mass index,
      declined from a mean of 3.3 (0.7 SD) at baseline to 2.9 (0.7 SD) (p<0.001) at
      follow-up 12 months after completion of the programme. There was no change in the
      waist:height ratio. Biomedical markers of blood glucose metabolism and lipid
      status remained in the normal range. 96% of the families completed the programme.
      CONCLUSIONS: This feasibility study of a 2-year family-based behavioural
      intervention programme in paediatric outpatient care showed promising results
      with regard to further weight gain and programme adherence. These findings must
      be confirmed in a randomised controlled trial with longer follow-up before the
      intervention programme can be implemented on a larger scale.

PMID- 22389358
TI  - Gender difference in the prognostic value of estimated glomerular filtration rate
      at admission in ST-segment elevation myocardial infarction: a prospective cohort
      study.
AB  - OBJECTIVE: To evaluate gender differences in the prognostic value of renal
      function for mortality in ST-segment elevation myocardial infarction (STEMI)
      patients undergoing primary percutaneous coronary intervention (PPCI). DESIGN:
      Prospective single-center cohort. SETTING: Single tertiary referral center in
      Amsterdam, The Netherlands. Patients consecutive STEMI patients undergoing PPCI
      (1412 men and 558 women). MAIN OUTCOME MEASURE: The authors calculated adjusted
      HRs for 3-year all-cause mortality according to the presence of a reduced renal
      function (estimated glomerular filtration rate <60 ml/min) using Cox proportional
      hazards models. In order to investigate a possible gender difference in the
      prognostic value of a reduced renal function, a comparison was made between the
      HRs of male and female patients and an interaction term was added to the model
      and tested for significance. Adjustments were made for age, body mass index,
      history of diabetes or hypertension, systolic blood pressure and heart rate,
      anterior myocardial infarction and time to treatment. RESULTS: In male patients,
      a reduced renal function was associated with increased 3-year mortality (adjusted
      HR 6.31, 95% CI 3.74 to 10.63, p<0.001). A reduced renal function was associated
      with a twofold increase in the mortality hazard in female patients (adjusted HR
      2.22, 95% CI 1.25 to 3.94, p=0.006). CONCLUSIONS: In this large single-centre
      registry of STEMI patients undergoing PPCI, renal dysfunction as assessed by
      estimated glomerular filtration rate had prognostic significance for mortality in
      both male and female patients.

PMID- 22389359
TI  - Factors predicting work status 3 months after injury: results from the
      Prospective Outcomes of Injury Study.
AB  - OBJECTIVE: Few studies examine predictors of work status following injury beyond
      injuries presenting to a hospital or emergency department. This paper examines
      the combined influences of socio-demographic, occupational, injury and pre
      existing health and lifestyle factors as predictors of work status 3 months after
      hospitalised and non-hospitalised injury in a cohort of injured New Zealand
      workers. DESIGN: Prospective cohort study. SETTING: The Prospective Outcomes of
      Injury Study, New Zealand. PARTICIPANTS: 2626 workforce active participants were
      identified from the Prospective Outcomes of Injury Study; 11 participants with
      missing outcome responses were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES:
      The primary outcome of interest was 'not working' at the time of interview.
      RESULTS: 720 (27%) reported 'not working' 3 months after injury. The most
      important pre-injury predictors of not working following injury found by
      multidimensional modelling were as follows: low or unknown income, financial
      insecurity, physical work tasks, temporary employment, long week schedules,
      obesity, perceived threat to life and hospital admission. Contrary to
      expectations, workers reporting less frequent exercise pre-injury had lower odds
      of work absence. Pre-injury psychosocial and health factors were not associated
      with not working. CONCLUSION: Certain pre-injury socio-demographic, physical
      work, work organisation, lifestyle and injury-related factors were associated
      with not working 3 months after injury. If these findings are confirmed,
      intervention strategies aimed at improving return to work should address multiple
      dimensions of both the worker and the workplace.

PMID- 22389360
TI  - Social and geographic inequalities in premature adult mortality in Japan: a
      multilevel observational study from 1970 to 2005.
AB  - OBJECTIVES: To examine trends in social and geographic inequalities in all-cause
      premature adult mortality in Japan. DESIGN: Observational study of the vital
      statistics and the census data. SETTING: Japan. PARTICIPANTS: Entire population
      aged 25 years or older and less than 65 years in 1970, 1975, 1980, 1985, 1990,
      1995, 2000 and 2005. The total number of decedents was 984 022 and 532 223 in men
      and women, respectively. MAIN OUTCOME MEASURES: For each sex, ORs and 95% CIs for
      mortality were estimated by using multilevel logistic regression models with
      'cells' (cross-tabulated by age and occupation) at level 1, 8 years at level 2
      and 47 prefectures at level 3. The prefecture-level variance was used as an
      estimate of geographic inequalities of mortality. RESULTS: Adjusting for age and
      time-trends, compared with production process and related workers, ORs ranged
      from 0.97 (95% CI 0.96 to 0.98) among administrative and managerial workers to
      2.22 (95% CI 2.19 to 2.24) among service workers in men. By contrast, in women,
      the lowest odds for mortality was observed among production process and related
      workers (reference), while the highest OR was 12.22 (95% CI 11.40 to 13.10) among
      security workers. The degree of occupational inequality increased in both sexes.
      Higher occupational groups did not experience reductions in mortality throughout
      the period and was overtaken by lower occupational groups in the early 1990s,
      among men. Conditional on individual age and occupation, overall geographic
      inequalities of mortality were relatively small in both sexes; the ORs ranged
      from 0.87 (Okinawa) to 1.13 (Aomori) for men and from 0.84 (Kanagawa) to 1.11
      (Kagoshima) for women, even though there is a suggestion of increasing
      inequalities across prefectures since 1995 in both sexes. CONCLUSIONS: The
      present findings suggest that both social and geographic inequalities in all
      cause mortality have increased in Japan during the last 3 decades.

PMID- 22389361
TI  - A method for early evaluation of a recently introduced technology by deriving a
      comparative group from existing clinical data: a case study in external support
      of the Marfan aortic root.
AB  - OBJECTIVE: During the early phase of evaluation of a new intervention, data exist
      for present practice. The authors propose a method of constructing a fair
      comparator group using these data. In this case study, the authors use the
      example of external aortic root support, a novel alternative to aortic root
      replacement. DESIGN: A matched comparison group, of similar age, aortic size and
      aortic valve function to those having the novel intervention, was constructed, by
      minimization, from among patients having conventional aortic root replacement in
      other hospitals during the same time frame. SETTING: Three cardiac surgical units
      in England. PATIENTS: The first 20 patients, aged 16-58 years with aortic root
      diameters of 40-54 mm, having external support surgery were compared with 20
      patients, aged 18-63 years and aortic root diameters of 38-58 mm, who had
      conventional aortic root replacement, between May 2004 and December 2009.
      INTERVENTIONS: A pliant external mesh sleeve, customised by computer-aided
      design, encloses the whole of the ascending aorta. The comparator group had
      conventional aortic root replacement, 16 valve-sparing and four with composite
      valved grafts. MAIN OUTCOME MEASURES: Duration of cardiopulmonary bypass (CPB),
      myocardial ischaemic time, blood loss and transfusion of blood, platelets and
      clotting factors. RESULTS: Comparing total root replacement and customised aortic
      root support surgery: CPB (median (range)) was 134 (52-316) versus 0 (0-20) min;
      myocardial ischaemia 114 (41-250) versus 0 (0-0) min; 4 h blood loss was 218 (85
      735) versus 50 (25-400) ml; and 9/18 had blood transfusion, 9/18 platelets and
      12/18 fresh frozen plasma after root replacement versus 1/20, 0/20 and 0/20,
      respectively, for the novel surgery. CONCLUSIONS: Avoidance or large reductions
      in CPB, myocardial ischaemia and blood product usage were achieved with the novel
      surgery. These data are of use in decision analysis and health economic
      evaluation and are available early in evaluation before randomised trial data are
      available.

PMID- 22389362
TI  - Prevalence and risk factors for forced or coerced sex among school-going youth:
      national cross-sectional studies in 10 southern African countries in 2003 and
      2007.
AB  - OBJECTIVES: To study prevalence at two time points and risk factors for
      experience of forced or coerced sex among school-going youth in 10 southern
      African countries. DESIGN: Cross-sectional surveys, by facilitated self
      administered questionnaire, of in-school youth in 2003 and 2007. SETTING: Schools
      serving representative communities in eight countries (Botswana, Lesotho, Malawi,
      Mozambique, Namibia, Swaziland, Zambia and Zimbabwe) in 2003 and with Tanzania
      and South Africa added in 2007. PARTICIPANTS: Students aged 11-16 years present
      in the school classes. MAIN OUTCOME MEASURES: Experience of forced or coerced
      sex, perpetration of forced sex. RESULTS: In 2007, 19.6% (4432/25 840) of female
      students and 21.1% (4080/21 613) of male students aged 11-16 years reported they
      had experienced forced or coerced sex. Rates among 16-year-olds were 28.8% in
      females and 25.4% in males. Comparing the same schools in eight countries, in an
      analysis age standardised on the 2007 Botswana male sample, there was no
      significant decrease between 2003 and 2007 among females in any country and
      inconsistent changes among males. In multilevel analysis using generalised linear
      mixed model, individual-level risk factors for forced sex among female students
      were age over 13 years and insufficient food in the household; school-level
      factors were a lower proportion of students knowing about child rights and higher
      proportions experiencing or perpetrating forced sex; and community-level factors
      were a higher proportion of adults in favour of transactional sex and a higher
      rate of intimate partner violence. Male risk factors were similar. Some 4.7% of
      female students and 11.7% of male students reported they had perpetrated forced
      sex. Experience of forced sex was strongly associated with perpetration and other
      risk factors for perpetration were similar to those for victimisation.
      CONCLUSIONS: Forced or coerced sex remained common among female and male youth in
      2007. Experience of sexual abuse in childhood is recognised to increase the risk
      of HIV infection. The association the authors found between forced sex and school
      level factors suggests preventive interventions in schools could help to tackle
      the HIV epidemic in southern Africa.

PMID- 22389363
TI  - Protocol: inspiratory muscle training for promoting recovery and outcomes in
      ventilated patients (IMPROVe): a randomised controlled trial.
AB  - INTRODUCTION: Inspiratory muscle weakness is a known consequence of mechanical
      ventilation and a potential contributor to difficulty in weaning from ventilatory
      support. Inspiratory muscle training (IMT) reduces the weaning period and
      increases the likelihood of successful weaning in some patients. However, it is
      not known how this training affects the residual inspiratory muscle fatigability
      following successful weaning nor patients' quality of life or functional
      outcomes. METHODS AND ANALYSIS: This dual centre study includes two concurrent
      randomised controlled trials of IMT in adult patients who are either currently
      ventilator-dependent (>7 days) (n=70) or have been recently weaned from
      mechanical ventilation (>7 days) in the past week (n=70). Subjects will be
      stable, alert and able to actively participate and provide consent. There will be
      concealed allocation to either treatment (IMT) or usual physiotherapy (including
      deep breathing exercises without a resistance device). Primary outcomes are
      inspiratory muscle fatigue resistance and maximum inspiratory pressures.
      Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional
      status (Acute Care Index of Function), rate of perceived exertion (Borg Scale),
      intensive care length of stay (days), post intensive care length of stay (days),
      rate of reintubation (%) and duration of ventilation (days). ETHICS AND
      DISSEMINATION: Ethics approval has been obtained from relevant institutions, and
      results will be published with a view to influencing physiotherapy practice in
      the management of long-term ventilator-dependent patients to accelerate weaning
      and optimise rehabilitation outcomes. TRIAL REGISTRATION NUMBER:
      ACTRN12610001089022.

PMID- 22389364
TI  - Housekeeping gene sequencing and multilocus variable-number tandem-repeat
      analysis to identify subpopulations within Pseudomonas syringae pv. maculicola
      and Pseudomonas syringae pv. tomato that correlate with host specificity.
AB  - Pseudomonas syringae pv. maculicola causes bacterial spot on Brassicaceae
      worldwide, and for the last 10 years severe outbreaks have been reported in the
      Loire Valley, France. P. syringae pv. maculicola resembles P. syringae pv. tomato
      in that it is also pathogenic for tomato and causes the same types of symptoms.
      We used a collection of 106 strains of P. syringae to characterize the
      relationships between P. syringae pv. maculicola and related pathovars, paying
      special attention to P. syringae pv. tomato. Phylogenetic analysis of gyrB and
      rpoD gene sequences showed that P. syringae pv. maculicola, which causes diseases
      in Brassicaceae, forms six genetic lineages within genomospecies 3 of P. syringae
      strains as defined by L. Gardan et al. (Int. J. Syst. Bacteriol. 49[Pt 2]:469
      478, 1999), whereas P. syringae pv. tomato forms two distinct genetic lineages. A
      multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) conducted with
      eight minisatellite loci confirmed the genetic structure obtained with rpoD and
      gyrB sequence analyses. These results provide promising tools for fine-scale
      epidemiological studies on diseases caused by P. syringae pv. maculicola and P.
      syringae pv. tomato. The two pathovars had distinct host ranges; only P. syringae
      pv. maculicola strains were pathogenic for Brassicaceae. A subpopulation of P.
      syringae pv. maculicola strains that are pathogenic for Pto-expressing tomato
      plants were shown to lack avrPto1 and avrPtoB or to contain a disrupted avrPtoB
      homolog. Taking phylogenetic and pathological features into account, our data
      suggest that the DC3000 strain belongs to P. syringae pv. maculicola. This study
      shows that P. syringae pv. maculicola and P. syringae pv. tomato appear
      multiclonal, as they did not diverge from a single common ancestral group within
      the ancestral P. syringae genomospecies 3, and suggests that pathovar specificity
      within P. syringae may be due to independent genetic events.

PMID- 22389365
TI  - Identification of potential type III secretion proteins via heterologous
      expression of Vibrio parahaemolyticus DNA.
AB  - We employed a heterologous secretion assay to identify proteins potentially
      secreted by type III secretion systems (T3SSs) in Vibrio parahaemolyticus. N
      terminal sequences from 32 proteins within T3SS genomic islands and seven
      proteins from elsewhere in the chromosome included proteins that were recognized
      for export by the Yersinia enterocolitica flagellar T3SS.

PMID- 22389367
TI  - Importance of Micromonospora spp. as colonizers of cellulose in freshwater lakes
      as demonstrated by quantitative reverse transcriptase PCR of 16S rRNA.
AB  - The relative abundance of micromonosporas in the bacterial communities inhabiting
      cellulose baits, water columns, and sediments of two freshwater lakes was
      determined by quantitative PCR (qPCR) of reverse-transcribed 16S rRNA.
      Micromonospora spp. were shown to be significant members of the active bacterial
      population colonizing cellulosic substrates in the lake sediment, and their
      increased prevalence with greater depth was confirmed by enumeration of CFU.

PMID- 22389366
TI  - Dimethyl sulfoxide and ethanol elicit increased amyloid biogenesis and amyloid
      integrated biofilm formation in Escherichia coli.
AB  - Escherichia coli directs the assembly of functional amyloid fibers termed "curli"
      that mediate adhesion and biofilm formation. We discovered that E. coli exhibits
      a tunable and selective increase in curli protein expression and fiber assembly
      in response to moderate concentrations of dimethyl sulfoxide (DMSO) and ethanol.
      Furthermore, the molecular alterations resulted in dramatic functional phenotypes
      associated with community behavior, including (i) cellular agglutination in
      broth, (ii) altered colony morphology, and (iii) increased biofilm formation.
      Solid-state nuclear magnetic resonance (NMR) spectra of intact pellicles formed
      in the presence of [(13)C(2)]DMSO confirmed that DMSO was not being transformed
      and utilized directly for metabolism. Collectively, the chemically induced
      phenotypes emphasize the plasticity of E. coli's response to environmental
      stimuli to enhance amyloid production and amyloid-integrated biofilm formation.
      The data also support our developing model of the extracellular matrix as an
      organized assembly of polymeric components, including amyloid fibers, in which
      composition relates to bacterial physiology and community function.

PMID- 22389368
TI  - Scaling down the analysis of environmental processes: monitoring enzyme activity
      in natural substrates on a millimeter resolution scale.
AB  - Natural environments often show high levels of spatial heterogeneity. With a
      methodology based on the immobilization of fluorescent substrates, the
      distribution of extracellular enzymes can be studied at a 2.3-mm resolution with
      a detection limit of 1.8 nmol . h(-1) . cm(-2). The method is applicable to
      environmental samples such as wood, litter, soil, or fungal colonies.

PMID- 22389369
TI  - Functional analysis of the degradation of cellulosic substrates by a Chaetomium
      globosum endophytic isolate.
AB  - Most photosynthetically fixed carbon is contained in cell wall polymers present
      in plant biomasses, the largest organic carbon source in the biosphere. The
      degradation of these polymers for biotechnological purposes requires the combined
      action of several enzymes. To identify new activities, we examined which enzymes
      are activated by an endophytic strain of Chaetomium globosum to degrade cellulose
      containing substrates. After biochemical analyses of the secretome of the fungus
      grown on cellulose or woody substrates, we took advantage of the available
      genomic data to identify potentially involved genes. After in silico
      identification of putative genes encoding either proteins able to bind to
      cellulose or glycohydrolases (GHs) of family 7, we investigated their transcript
      levels by reverse transcription-quantitative PCR (RT-qPCR). Our data suggest that
      eight genes compose the core of the cellulose-degrading system of C. globosum.
      Notably, the related enzymes belong structurally to the well-described GH
      families 5, 6, 7, 16, and 45, which are known to be the core of the cellulose
      degradation systems of several ascomycetes. The high expression levels of
      cellobiose dehydrogenase and two GH 61 enzymes suggest the involvement of this
      oxidoreductive synergic system in C. globosum. Transcript analysis along with
      relevant coding sequence (CDS) isolation and expression of recombinant proteins
      proved to be a key strategy for the determination of the features of two
      endoglucanases used by C. globosum for the first attack of crystalline cellulose.
      Finally, the possible involvement of transcriptional regulators described for
      other ascomycetes is discussed.

PMID- 22389370
TI  - Complex physiology and compound stress responses during fermentation of alkali
      pretreated corn stover hydrolysate by an Escherichia coli ethanologen.
AB  - The physiology of ethanologenic Escherichia coli grown anaerobically in alkali
      pretreated plant hydrolysates is complex and not well studied. To gain insight
      into how E. coli responds to such hydrolysates, we studied an E. coli K-12
      ethanologen fermenting a hydrolysate prepared from corn stover pretreated by
      ammonia fiber expansion. Despite the high sugar content (~6% glucose, 3% xylose)
      and relatively low toxicity of this hydrolysate, E. coli ceased growth long
      before glucose was depleted. Nevertheless, the cells remained metabolically
      active and continued conversion of glucose to ethanol until all glucose was
      consumed. Gene expression profiling revealed complex and changing patterns of
      metabolic physiology and cellular stress responses during an exponential growth
      phase, a transition phase, and the glycolytically active stationary phase. During
      the exponential and transition phases, high cell maintenance and stress response
      costs were mitigated, in part, by free amino acids available in the hydrolysate.
      However, after the majority of amino acids were depleted, the cells entered
      stationary phase, and ATP derived from glucose fermentation was consumed entirely
      by the demands of cell maintenance in the hydrolysate. Comparative gene
      expression profiling and metabolic modeling of the ethanologen suggested that the
      high energetic cost of mitigating osmotic, lignotoxin, and ethanol stress
      collectively limits growth, sugar utilization rates, and ethanol yields in alkali
      pretreated lignocellulosic hydrolysates.

PMID- 22389371
TI  - Toward homosuccinate fermentation: metabolic engineering of Corynebacterium
      glutamicum for anaerobic production of succinate from glucose and formate.
AB  - Previous studies have demonstrated the capability of Corynebacterium glutamicum
      for anaerobic succinate production from glucose under nongrowing conditions. In
      this work, we have addressed two shortfalls of this process, the formation of
      significant amounts of by-products and the limitation of the yield by the redox
      balance. To eliminate acetate formation, a derivative of the type strain ATCC
      13032 (strain BOL-1), which lacked all known pathways for acetate and lactate
      synthesis (Deltacat Deltapqo Deltapta-ackA DeltaldhA), was constructed.
      Chromosomal integration of the pyruvate carboxylase gene pyc(P458S) into BOL-1
      resulted in strain BOL-2, which catalyzed fast succinate production from glucose
      with a yield of 1 mol/mol and showed only little acetate formation. In order to
      provide additional reducing equivalents derived from the cosubstrate formate, the
      fdh gene from Mycobacterium vaccae, coding for an NAD(+)-coupled formate
      dehydrogenase (FDH), was chromosomally integrated into BOL-2, leading to strain
      BOL-3. In an anaerobic batch process with strain BOL-3, a 20% higher succinate
      yield from glucose was obtained in the presence of formate. A temporary metabolic
      blockage of strain BOL-3 was prevented by plasmid-borne overexpression of the
      glyceraldehyde 3-phosphate dehydrogenase gene gapA. In an anaerobic fed-batch
      process with glucose and formate, strain BOL-3/pAN6-gap accumulated 1,134 mM
      succinate in 53 h with an average succinate production rate of 1.59 mmol per g
      cells (dry weight) (cdw) per h. The succinate yield of 1.67 mol/mol glucose is
      one of the highest currently described for anaerobic succinate producers and was
      accompanied by a very low level of by-products (0.10 mol/mol glucose).

PMID- 22389372
TI  - Selection of a Bifidobacterium animalis subsp. lactis strain with a decreased
      ability to produce acetic acid.
AB  - We have characterized a new strain, Bifidobacterium animalis subsp. lactis CECT
      7953, obtained by random UV mutagenesis, which produces less acetic acid than the
      wild type (CECT 7954) in three different experimental settings: De Man-Rogosa
      Sharpe broth without sodium acetate, resting cells, and skim milk. Genome
      sequencing revealed a single Phe-Ser substitution in the acetate kinase gene
      product that seems to be responsible for the strain's reduced acid production.
      Accordingly, acetate kinase specific activity was lower in the low acetate
      producer. Strain CECT 7953 produced less acetate, less ethanol, and more yoghourt
      related volatile compounds in skim milk than the wild type did. Thus, CECT 7953
      shows promising potential for the development of dairy products fermented
      exclusively by a bifidobacterial strain.

PMID- 22389373
TI  - Analysis of structure and composition of bacterial core communities in mature
      drinking water biofilms and bulk water of a citywide network in Germany.
AB  - The bacterial core communities of bulk water and corresponding biofilms of a more
      than 20-year-old drinking water network were compared using 16S rRNA single
      strand confirmation polymorphism (SSCP) fingerprints based on extracted DNA and
      RNA. The structure and composition of the bacterial core community in the bulk
      water was highly similar (>70%) across the city of Braunschweig, Germany, whereas
      all biofilm samples contained a unique community with no overlapping phylotypes
      from bulk water. Biofilm samples consisted mainly of Alphaproteobacteria (26% of
      all phylotypes), Gammaproteobacteria (11%), candidate division TM6 (11%),
      Chlamydiales (9%), and Betaproteobacteria (9%). The bulk water community
      consisted primarily of Bacteroidetes (25%), Betaproteobacteria (20%),
      Actinobacteria (16%), and Alphaproteobacteria (11%). All biofilm communities
      showed higher relative abundances of single phylotypes and a reduced richness
      compared to bulk water. Only biofilm communities sampled at nearby sampling
      points showed similar communities irrespective of support materials. In all of
      our bulk water studies, the community composition determined from 16S rRNA was
      completely different from the 16S rRNA gene-based community composition, whereas
      in biofilms both molecular fractions resulted in community compositions that were
      similar to each other. We hypothesize that a higher fraction of active bacterial
      phylotypes and a better protection from oxidative stress in drinking water
      biofilms are responsible for this higher similarity.

PMID- 22389374
TI  - Evidence of host-associated populations of Cryptosporidium parvum in Italy.
AB  - Recent studies have revealed extensive genetic variation among isolates of
      Cryptosporidium parvum, an Apicomplexan parasite that causes gastroenteritis in
      both humans and animals worldwide. The parasite's population structure is
      influenced by the intensity of transmission, the host-parasite interaction, and
      husbandry practices. As a result, C. parvum populations can be panmictic, clonal,
      or even epidemic on both a local scale and a larger geographical scale. To extend
      the study of C. parvum populations to an unexplored region, 173 isolates of C.
      parvum collected in Italy from humans and livestock (calf, sheep, and goat) over
      a 10-year period were genotyped using a multilocus scheme based on 7 mini- and
      microsatellite loci. In agreement with other studies, extensive polymorphism was
      observed, with 102 distinct multilocus genotypes (MLGs) identified among 173
      isolates. The presence of linkage disequilibrium, the confinement of MLGs to
      individual farms, and the relationship of many MLGs inferred using network
      analysis (eBURST) suggest a predominantly clonal population structure, but there
      is also evidence that part of the diversity can be explained by genetic exchange.
      MLGs from goats were found to differ from bovine and sheep MLGs, supporting the
      existence of C. parvum subpopulations. Finally, MLGs from isolates collected
      between 1997 and 1999 were also identified as a distinct subgroup in principal
      component analysis and eBURST analysis, suggesting a continuous introduction of
      novel genotypes in the parasite population.

PMID- 22389375
TI  - Detection of a common and persistent tet(L)-carrying plasmid in chicken-waste
      impacted farm soil.
AB  - The connection between farm-generated animal waste and the dissemination of
      antibiotic resistance in soil microbial communities, via mobile genetic elements,
      remains obscure. In this study, electromagnetic induction (EMI) surveying of a
      broiler chicken farm assisted soil sampling from a chicken-waste-impacted site
      and a marginally affected site. Consistent with the EMI survey, a disparity
      existed between the two sites with regard to soil pH, tetracycline resistance
      (Tc(r)) levels among culturable soil bacteria, and the incidence and prevalence
      of several tet and erm genes in the soils. No significant difference was observed
      in these aspects between the marginally affected site and several sites in a
      relatively pristine regional forest. When the farm was in operation, tet(L),
      tet(M), tet(O), erm(A), erm(B), and erm(C) genes were detected in the waste
      affected soil. Two years after all waste was removed from the farm, tet(L),
      tet(M), tet(O), and erm(C) genes were still detected. The abundances of tet(L),
      tet(O), and erm(B) were measured using quantitative PCR, and the copy numbers of
      each were normalized to eubacterial 16S rRNA gene copy numbers. tet(L) was the
      most prevalent gene, whereas tet(O) was the most persistent, although all
      declined over the 2-year period. A mobilizable plasmid carrying tet(L) was
      identified in seven of 14 Tc(r) soil isolates. The plasmid's hosts were
      identified as species of Bhargavaea, Sporosarcina, and Bacillus. The plasmid's
      mobilization (mob) gene was quantified to estimate its prevalence in the soil,
      and the ratio of tet(L) to mob was shown to have changed from 34:1 to 1:1 over
      the 2-year sampling period.

PMID- 22389376
TI  - Composting for avian influenza virus elimination.
AB  - Effective sanitization is important in viral epizootic outbreaks to avoid further
      spread of the pathogen. This study examined thermal inactivation as a sanitizing
      treatment for manure inoculated with highly pathogenic avian influenza virus H7N1
      and bacteriophages MS2 and 6. Rapid inactivation of highly pathogenic avian
      influenza virus H7N1 was achieved at both mesophilic (35 degrees C) and
      thermophilic (45 and 55 degrees C) temperatures. Similar inactivation rates were
      observed for bacteriophage 6, while bacteriophage MS2 proved too thermoresistant
      to be considered a valuable indicator organism for avian influenza virus during
      thermal treatments. Guidelines for treatment of litter in the event of emergency
      composting can be formulated based on the inactivation rates obtained in the
      study.

PMID- 22389377
TI  - Improved thermostability of Clostridium thermocellum endoglucanase Cel8A by using
      consensus-guided mutagenesis.
AB  - The use of thermostable cellulases is advantageous for the breakdown of
      lignocellulosic biomass toward the commercial production of biofuels. Previously,
      we have demonstrated the engineering of an enhanced thermostable family 8
      cellulosomal endoglucanase (EC 3.2.1.4), Cel8A, from Clostridium thermocellum,
      using random error-prone PCR and a combination of three beneficial mutations,
      dominated by an intriguing serine-to-glycine substitution (M. Anbar, R. Lamed, E.
      A. Bayer, ChemCatChem 2:997-1003, 2010). In the present study, we used a
      bioinformatics-based approach involving sequence alignment of homologous family 8
      glycoside hydrolases to create a library of consensus mutations in which residues
      of the catalytic module are replaced at specific positions with the most
      prevalent amino acids in the family. One of the mutants (G283P) displayed a
      higher thermal stability than the wild-type enzyme. Introducing this mutation
      into the previously engineered Cel8A triple mutant resulted in an optimized
      enzyme, increasing the half-life of activity by 14-fold at 85 degrees C.
      Remarkably, no loss of catalytic activity was observed compared to that of the
      wild-type endoglucanase. The structural changes were simulated by molecular
      dynamics analysis, and specific regions were identified that contributed to the
      observed thermostability. Intriguingly, most of the proteins used for sequence
      alignment in determining the consensus residues were derived from mesophilic
      bacteria, with optimal temperatures well below that of C. thermocellum Cel8A.

PMID- 22389378
TI  - Detection of two zoonotic Babesia microti lineages, the Hobetsu and U.S.
      lineages, in two sympatric tick species, ixodes ovatus and Ixodes persulcatus,
      respectively, in Japan.
AB  - The species Babesia microti, commonly found in rodents, demonstrates a high
      degree of genetic diversity. Three lineages, U.S., Kobe, and Hobetsu, are known
      to have zoonotic potential, but their tick vector(s) in Japan remains to be
      elucidated. We conducted a field investigation at Nemuro on Hokkaido Island and
      at Sumoto on Awaji Island, where up to two of the three lineages occur with
      similar frequencies in reservoirs. By flagging vegetation at these spots and
      surrounding areas, 4,010 ticks, comprising six species, were collected. A nested
      PCR that detects the 18S rRNA gene of Babesia species revealed that Ixodes ovatus
      and I. persulcatus alone were positive. Lineage-specific PCR for rRNA-positive
      samples demonstrated that I. ovatus and I. persulcatus carried, respectively, the
      Hobetsu and U.S. parasites. No Kobe-specific DNA was detected. Infected I. ovatus
      ticks were found at multiple sites, including Nemuro and Sumoto, with minimum
      infection rates (MIR) of ~12.3%. However, all I. persulcatus ticks collected
      within the same regions, a total of 535, were negative for the Hobetsu lineage,
      indicating that I. ovatus, but not I. persulcatus, was the vector for the
      lineage. At Nemuro, U.S. lineage was detected in 2 of 139 adult I. persulcatus
      ticks (MIR, 1.4%), for the first time, while 48 of I. ovatus ticks were negative
      for that lineage. Laboratory experiments confirmed the transmission of Hobetsu
      and U.S. parasites to hamsters via I. ovatus and I. persulcatus, respectively.
      Differences in vector capacity shown by MIRs at Nemuro, where the two species
      were equally likely to acquire either lineage of parasite, may explain the
      difference in distribution of Hobetsu throughout Japan and U.S. taxa in Nemuro.
      These findings are of importance in the assessment of the regional risk for
      babesiosis in humans.

PMID- 22389379
TI  - Irrigation differentially impacts populations of indigenous antibiotic-producing
      pseudomonas spp. in the rhizosphere of wheat.
AB  - This work determined the impact of irrigation on the seasonal dynamics of
      populations of Pseudomonas spp. producing the antibiotics phenazine-1-carboxylic
      acid (Phz(+)) and 2,4-diacetylphloroglucinol (Phl(+)) in the rhizosphere of wheat
      grown in the low-precipitation zone (150 to 300 mm annually) of the Columbia
      Plateau of the Inland Pacific Northwest. Population sizes and plant colonization
      frequencies of Phz(+) and Phl(+) Pseudomonas spp. were determined in winter and
      spring wheat collected during the growing seasons from 2008 to 2009 from selected
      commercial dryland and irrigated fields in central Washington State. Only Phz(+)
      bacteria were detected on dryland winter wheat, with populations ranging from 4.8
      to 6.3 log CFU g(-1) of root and rhizosphere colonization frequencies of 67 to
      100%. The ranges of population densities of Phl(+) and Phz(+) Pseudomonas spp.
      recovered from wheat grown under irrigation were similar, but 58 to 100% of root
      systems were colonized by Phl(+) bacteria whereas only 8 to 50% of plants
      harbored Phz(+) bacteria. In addition, Phz(+) Pseudomonas spp. were abundant in
      the rhizosphere of native plant species growing in nonirrigated areas adjacent to
      the sampled dryland wheat fields. This is the first report that documents the
      impact of irrigation on indigenous populations of two closely related groups of
      antibiotic-producing pseudomonads that coinhabit the rhizosphere of an
      economically important cereal crop. These results demonstrate how crop management
      practices can influence indigenous populations of antibiotic-producing
      pseudomonads with the capacity to suppress soilborne diseases of wheat.

PMID- 22389380
TI  - Population pharmacokinetics of single-dose intravenous paracetamol in children.
AB  - BACKGROUND: To determine the pharmacokinetics (PK) of a new i.v. formulation of
      paracetamol (Perfalgan) in children <=15 yr of age. METHODS: After obtaining
      written informed consent, children under 16 yr of age were recruited to this
      study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after
      administration of a weight-dependent dose of i.v. paracetamol. Paracetamol
      concentration was measured using a validated high-performance liquid
      chromatographic assay with ultraviolet detection method, with a lower limit of
      quantification (LLOQ) of 900 pg on column and an intra-day coefficient of
      variation of 14.3% at the LLOQ. Population PK analysis was performed by non
      linear mixed-effect modelling using NONMEM. RESULTS: One hundred and fifty-nine
      blood samples from 33 children aged 1.8-15 yr, weight 13.7-56 kg, were analysed.
      Data were best described by a two-compartment model. Only body weight as a
      covariate significantly improved the goodness of fit of the model. The final
      population models for paracetamol clearance (CL), V(1) (central volume of
      distribution), Q (inter-compartmental clearance), and V(2) (peripheral volume of
      distribution) were: 16.51*(WT/70)(0.75), 28.4*(WT/70), 11.32*(WT/70)(0.75), and
      13.26*(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V(1)
      and V(2) in litres). CONCLUSIONS: In children aged 1.8-15 yr, the PK parameters
      for i.v. paracetamol were not influenced directly by age but were by total body
      weight and, using allometric size scaling, significantly affected the clearances
      (CL, Q) and volumes of distribution (V(1), V(2)).

PMID- 22389381
TI  - Metformin inhibits growth and decreases resistance to anoikis in medullary
      thyroid cancer cells.
AB  - Medullary thyroid cancer (MTC) is associated with activation of mammalian target
      of rapamycin (mTOR) signaling pathways. Recent studies showed that the
      antidiabetic agent metformin decreases proliferation of cancer cells through 5'
      AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR. In the current
      study, we assessed the effect of metformin on MTC cells. For this purpose, we
      determined growth, viability, migration, and resistance to anoikis assays using
      two MTC-derived cell lines (TT and MZ-CRC-1). Expressions of molecular targets of
      metformin were examined in MTC cell lines and in 14 human MTC tissue samples. We
      found that metformin inhibited growth and decreased expression of cyclin D1 in
      MTC cells. Treatment with metformin was associated with inhibition of
      mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1
      cells. Metformin had no significant effects on pAKT in the cell lines examined.
      Metformin-inducible AMPK activation was noted only in TT cells. Treatment with
      AMPK inhibitor (compound C) or AMPK silencing did not prevent growth inhibitory
      effects of metformin in TT cells. Metformin had no effect on MTC cell migration
      but reduced the ability of cells to form multicellular spheroids in nonadherent
      conditions. Immunostaining of human MTC showed over-expression of cyclin D1 in
      all tumors compared with corresponding normal tissue. Activation of mTOR/p70S6K
      was detected in 8/14 (57.1%) examined tumors. Together, these findings indicate
      that growth inhibitory effects in MTC cells are associated with downregulation of
      both mTOR/6SK and pERK signaling pathways. Expression of metformin's molecular
      targets in human MTC cells suggests its potential utility for the treatment of
      MTC in patients.

PMID- 22389382
TI  - Common genetic variants in metabolism and detoxification pathways and the risk of
      papillary thyroid cancer.
AB  - Relationships are unclear between polymorphisms in genes involved in metabolism
      and detoxification of various chemicals and papillary thyroid cancer (PTC) risk
      as well as their potential modification by alcohol or tobacco intake. We
      evaluated associations between 1647 tagging single nucleotide polymorphisms
      (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and
      endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways)
      and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their
      respective SNPs, we also assessed interaction with alcohol and tobacco use.
      Logistic regression models were used to evaluate the main effect of SNPs
      (P(trend)) and interaction with alcohol/tobacco intake. Gene- and pathway-level
      associations and interactions (P(gene interaction)) were evaluated by combining
      P(trend) values using the adaptive rank-truncated product method. While we found
      associations between PTC risk and nine SNPs (P(trend) <= 0.01) and seven
      genes/regions (P(region)<0.05), none remained significant after correction for
      the false discovery rate. We found a significant interaction between UGT2B7 and
      NAT1 genes and alcohol intake (P(gene interaction)=0.01 and 0.02 respectively)
      and between the CYP26B1 gene and tobacco intake (P(gene interaction)=0.02). Our
      results are suggestive of interaction between the genetic polymorphisms in
      several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger
      studies with improved exposure assessment should address potential modification
      of PTC risk by alcohol and tobacco intake to confirm or refute our findings.

PMID- 22389383
TI  - Pathogenesis of prostatic small cell carcinoma involves the inactivation of the
      P53 pathway.
AB  - Small cell neuroendocrine carcinoma (SCNC) of the prostate is a variant form of
      prostate cancer that occurs de novo or as a recurrent tumor in patients who
      received hormonal therapy for prostatic adenocarcinoma. It is composed of pure
      neuroendocrine (NE) tumor cells, but unlike the scattered NE cells in benign
      prostate and adenocarcinoma that are quiescent, the NE cells in SCNC are highly
      proliferative and aggressive, causing death in months. In this study, we provide
      evidence that interleukin 8 (IL8)-CXCR2-P53 (TP53) signaling pathway keeps the NE
      cells of benign prostate and adenocarcinoma in a quiescent state normally. While
      P53 appears to be wild-type in the NE cells of benign prostate and
      adenocarcinoma, immunohistochemical studies show that the majority of the NE
      tumor cells in SCNC are positive for nuclear p53, suggesting that the p53 is
      mutated. This observation is confirmed by sequencing of genomic DNA showing p53
      mutation in five of seven cases of SCNC. Our results support the hypothesis that
      p53 mutation leads to inactivation of the IL8-CXCR2-p53 signaling pathway,
      resulting in the loss of an important growth inhibitory mechanism and the hyper
      proliferation of NE cells in SCNC. Therefore, we have identified potential cells
      of origin and a molecular target for prostatic SCNC that are very different from
      those of conventional adenocarcinoma, which explains SCNC's distinct biology and
      the clinical observation that it does not respond to hormonal therapy targeting
      androgen receptor signaling, which produces short-term therapeutic effects in
      nearly all patients with prostatic adenocarcinoma.

PMID- 22389384
TI  - A surface glycoprotein indispensable for gamete fusion in the social amoeba
      Dictyostelium discoideum.
AB  - Sexual reproduction is essential for the maintenance of species in a wide variety
      of multicellular organisms, and even unicellular organisms that normally
      proliferate asexually possess a sexual cycle because of its contribution to
      increased genetic diversity. Information concerning the molecules involved in
      fertilization is accumulating for many species of the metazoan, plant, and fungal
      lineages, and the evolutionary consideration of sexual reproduction systems is
      now an interesting issue. Macrocyst formation in the social amoeba Dictyostelium
      discoideum is a sexual process in which cells become sexually mature under dark
      and submerged conditions and fuse with complementary mating-type cells. In the
      present study, we isolated D. discoideum insertional mutants defective in sexual
      cell fusion and identified the relevant gene, macA, which encodes a highly
      glycosylated, 2,041-amino-acid membrane protein (MacA). Although its overall
      similarity is restricted to proteins of unknown function within dictyostelids, it
      contains LamGL and discoidin domains, which are implicated in cell adhesion. The
      growth and development of macA-null mutants were indistinguishable from those of
      the parental strain. The overexpression of macA using the V18 promoter in a macA
      null mutant completely restored its sexual defects. Although the macA gene
      encoded exactly the same protein in a complementary mating-type strain, it was
      expressed at a much lower level. These results suggest that MacA is indispensable
      for gamete interactions in D. discoideum, probably via cell adhesion. There is a
      possibility that it is controlled in a mating-type-dependent manner.

PMID- 22389385
TI  - The trypanosomatid-specific N terminus of RPA2 is required for RNA polymerase I
      assembly, localization, and function.
AB  - African trypanosomes are the only organisms known to use RNA polymerase I (pol I)
      to transcribe protein-coding genes. These genes include VSG, which is essential
      for immune evasion and is transcribed from an extranucleolar expression site body
      (ESB). Several trypanosome pol I subunits vary compared to their homologues
      elsewhere, and the question arises as to how these variations relate to pol I
      function. A clear example is the N-terminal extension found on the second-largest
      subunit of pol I, RPA2. Here, we identify an essential role for this region. RPA2
      truncation leads to nuclear exclusion and a growth defect which phenocopies
      single-allele knockout. The N terminus is not a general nuclear localization
      signal (NLS), however, and it fails to accumulate unrelated proteins in the
      nucleus. An ectopic NLS is sufficient to reinstate nuclear localization of
      truncated RPA2, but it does not restore function. Moreover, NLS-tagged, truncated
      RPA2 has a different subnuclear distribution to full-length protein and is unable
      to build stable pol I complexes. We conclude that the RPA2 N-terminal extension
      does not have a role exclusive to the expression of protein-coding genes, but it
      is essential for all pol I functions in trypanosomes because it directs
      trypanosomatid-specific interactions with RPA1.

PMID- 22389386
TI  - Heart angiotensin II-induced cardiomyocyte hypertrophy suppresses coronary
      angiogenesis and progresses diabetic cardiomyopathy.
AB  - To examine whether and how heart ANG II influences the coordination between
      cardiomyocyte hypertrophy and coronary angiogenesis and contributes to the
      pathogenesis of diabetic cardiomyopathy, we used Spontaneously Diabetic Torii
      (SDT) rats treated without and with olmesartan medoxomil (an ANG II receptor
      blocker). In SDT rats, left ventricular (LV) ANG II, but not circulating ANG II,
      increased at 8 and 16 wk after diabetes onset. SDT rats developed LV hypertrophy
      and diastolic dysfunction at 8 wk, followed by LV systolic dysfunction at 16 wk,
      without hypertension. The SDT rat LV exhibited cardiomyocyte hypertrophy and
      increased hypoxia-inducible factor-1alpha expression at 8 wk and to a greater
      degree at 16 wk and interstitial fibrosis at 16 wk only. In SDT rats, coronary
      angiogenesis increased with enhanced capillary proliferation and upregulation of
      the angiogenic factor VEGF at 8 wk but decreased VEGF with enhanced capillary
      apoptosis and suppressed capillary proliferation despite the upregulation of VEGF
      at 16 wk. In SDT rats, the phosphorylation of VEGF receptor-2 increased at 8 wk
      alone, whereas the expression of the antiangiogenic factor thrombospondin-1
      increased at 16 wk alone. All these events, except for hyperglycemia or blood
      pressure, were reversed by olmesartan medoxomil. These results suggest that LV
      ANG II in SDT rats at 8 and 16 wk induces cardiomyocyte hypertrophy without
      affecting hyperglycemia or blood pressure, which promotes and suppresses coronary
      angiogenesis, respectively, via VEGF and thrombospondin-1 produced from
      hypertrophied cardiomyocytes under chronic hypoxia. Thrombospondin-1 may play an
      important role in the progression of diabetic cardiomyopathy in this model.

PMID- 22389387
TI  - HDAC4 mediates development of hypertension via vascular inflammation in
      spontaneous hypertensive rats.
AB  - Histone deacetylases (HDACs) are transcriptional corepressors. Our recent study
      demonstrated that HDAC4 protein specifically increases in mesenteric artery from
      spontaneous hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY).
      Vascular inflammation is important for pathogenesis of hypertension. We examined
      whether HDAC4 affects vascular inflammatory responses and promotes hypertension.
      In vivo, blood pressure, reactive oxygen species (ROS) production, and VCAM-1
      expression in isolated mesenteric artery were elevated in young SHR (7 wk old)
      compared with age-matched WKY, which were prevented by long-term treatment of SHR
      with an HDACs inhibitor, trichostatin A (TSA; 500 MUg.kg(-1).day(-1) for 3 wk).
      In isolated mesenteric artery, the increased angiotensin II-induced contraction
      in SHR was reversed by TSA. The endothelium-dependent relaxation induced by ACh
      in SHR was augmented by TSA. In cultured rat mesenteric arterial smooth muscle
      cells (SMCs), expression of HDAC4 mRNA and protein was increased by TNF-alpha (10
      ng/ml). TSA (10 MUM, pretreatment for 30 min) inhibited VCAM-1 expression and NF
      kappaB phosphorylation induced by TNF (10 ng/ml, 24 h or 20 min) in SMCs. HDAC4
      small interfering RNA inhibited TNF-induced monocyte adhesion, VCAM-1 expression,
      transcriptional activity of NF-kappaB, and ROS production in SMCs. The present
      results demonstrated that proinflammatory effects of HDACs may mediate the
      further development of hypertension in SHR. It is also suggested in cultured
      vascular SMCs that TNF-induced HDAC4 mediates vascular inflammation likely via
      VCAM-1 induction through ROS-dependent NF-kappaB activation.

PMID- 22389390
TI  - Blockers of the renin-angiotensin-aldosterone system: almost, but not yet, an
      absolute weapon against cardiovascular and renal diseases!

PMID- 22389389
TI  - Finger photoplethysmography during the Valsalva maneuver reflects left
      ventricular filling pressure.
AB  - It is often challenging to assess cardiac filling pressure clinically. An
      improved system for detecting or ruling out elevated cardiac filling pressure may
      help reduce hospitalizations for heart failure. The blood pressure response to
      the Valsalva maneuver reflects left heart filling pressure, but its underuse
      clinically may be due in part to lack of continuous blood pressure recording
      along with lack of standardization of expiratory effort. In this study, we tested
      whether Valsalva-induced changes in the pulse amplitude of finger
      photoplethysmography (PPG), a technology already widely available in medical
      settings, correlate with invasively measured left ventricular end-diastolic
      pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac
      catheterizations. A finger photoplethysmography waveform was recorded during a
      Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most
      patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG
      waveform amplitude just before release of expiratory effort divided by the
      waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P <
      0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95%
      confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In
      conclusion, finger PPG, a technology already ubiquitous in medical centers, may
      be useful for assessing clinically meaningful categories of left heart filling
      pressure, using simple analysis of the waveform after a Valsalva maneuver effort
      that most patients can achieve.

PMID- 22389388
TI  - Altered expression of mitochondrial electron transport chain proteins and
      improved myocardial energetic state during late ischemic preconditioning.
AB  - Altered expression of mitochondrial electron transport proteins has been shown in
      early preconditioned myocardial tissue. We wished to determine whether these
      alterations persist in the Second Window of Protection (SWOP) and if so, whether
      a favorable energetic state is facilitated during subsequent ischemia. Fourteen
      pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD
      artery, each separated by 2 minutes reperfusion. Twenty-four hours later,
      mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for
      uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by
      iTRAQ((r)) and respiration by an oxygen electrode. In parallel in vivo studies,
      high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP
      and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with
      SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of
      UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In
      comparison with SHAM pigs during in vivo conditions, transmural energetics in
      SWOP hearts, as estimated by the free energy of ATP hydrolysis (DeltaG(0)), were
      similar at baseline but had decreased by the end of low-flow ischemia (-57.0 +/-
      2.1 versus -51.1 +/- 1.4 kJ/mol; P < 0.05). In conclusion, within isolated
      mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert
      with enhanced Complex IV and V proteins, imparts a favorable energetic state
      during low-flow ischemia. These data support the notion that mitochondrial
      adaptations that may reduce oxidant damage do not reduce the overall efficiency
      of energetics during sustained oxygen deprivation.

PMID- 22389391
TI  - Cardiorenal disease development under chronic renin-angiotensin-aldosterone
      system suppression.
AB  - Drugs suppressing the renin-angiotensin-aldosterone system (RAAS) are now widely
      used to treat patients all along the cardiorenal continuum. It supposes that many
      patients, in particular those with arterial hypertension are treated with
      converting-enzyme inhibitors and angiotensin receptor blockers for years during
      which the development and prograssion of cardiorenal disease can be observed. The
      meaning of this progression in the presence of RAAS suppression requires to be
      clarified and to be treated in order to diminish the velocity of progression of
      cardiorenal disease.

PMID- 22389393
TI  - Non-canonical ubiquitin-based signals for proteasomal degradation.
AB  - Regulated cellular proteolysis is mediated largely by the ubiquitin-proteasome
      system (UPS). It is a highly specific process that is time- (e.g. cell cycle),
      compartment- (e.g. nucleus or endoplasmic reticulum) and substrate quality- (e.g.
      denatured or misfolded proteins) dependent, and allows fast adaptation to
      changing conditions. Degradation by the UPS is carried out through two successive
      steps: the substrate is covalently tagged with ubiquitin and subsequently
      degraded by the 26S proteasome. The accepted 'canonical' signal for proteasomal
      recognition is a polyubiquitin chain that is anchored to a lysine residue in the
      target substrate, and is assembled through isopeptide bonds involving lysine 48
      of ubiquitin. However, several 'non-canonical' ubiquitin-based signals for
      proteasomal targeting have also been identified. These include chains anchored to
      residues other than internal lysine in the substrates, chains assembled through
      linking residues other than lysine 48 in ubiquitin, and mixed chains made of both
      ubiquitin and a ubiquitin-like protein. Furthermore, some proteins can be
      degraded following modification by a single ubiquitin (monoubiquitylation) or
      multiple single ubiquitins (multiple monoubiquitylation). Finally, some proteins
      can be proteasomally degraded without prior ubiquitylation (the process is also
      often referred to as ubiquitination). In this Commentary, we describe these
      recent findings and discuss the possible physiological roles of these diverse
      signals. Furthermore, we discuss the possible impact of this signal diversity on
      drug development.

PMID- 22389394
TI  - No one can whistle a symphony alone - how different ubiquitin linkages cooperate
      to orchestrate NF-kappaB activity.
AB  - Although it has been known for a long time that ubiquitylation has a major role
      in the activation and regulation of the nuclear factor kappa B (NF-kappaB)
      pathway, recent studies have revealed that the picture is a lot more complex than
      originally thought. NF-kappaB and ubiquitylation initially became linked when it
      was recognised that lysine (K)48-linked ubiquitin chains are involved in the
      processing of NF-kappaB precursors and the degradation of inhibitor of kappa B
      (IkappaB) proteins. Soon thereafter, it was reported that K63-linked chains were
      involved in the assembly of IkappaB kinase (IKK)-activating complexes and
      required for activation of the NF-kappaB signalling pathway. Recently, the
      discovery that atypical ubiquitin linkages, including linear and K11 linkages,
      are also involved in the activation of NF-kappaB has led to the need to re
      evaluate existing models of how activation of this transcription factor is
      initiated and regulated. It is now becoming apparent that not only the canonical
      types of ubiquitin chains but possibly all linkage types have to be investigated
      in order to fully comprehend NF-kappaB activation. This can be considered a
      turning point in our view of the regulation of one of the most important pathways
      of gene induction. Hence, in this Commentary, we summarise the information that
      is currently available and incorporate it into a new model of NF-kappaB
      activation, thereby highlighting the emerging new challenges in understanding the
      role of ubiquitylation in NF-kappaB activation.

PMID- 22389392
TI  - HECT and RING finger families of E3 ubiquitin ligases at a glance.

PMID- 22389396
TI  - Super-resolution imaging visualizes the eightfold symmetry of gp210 proteins
      around the nuclear pore complex and resolves the central channel with nanometer
      resolution.
AB  - One of the most complex molecular machines of cells is the nuclear pore complex
      (NPC), which controls all trafficking of molecules in and out of the nucleus.
      Because of their importance for cellular processes such as gene expression and
      cytoskeleton organization, the structure of NPCs has been studied extensively
      during the last few decades, mainly by electron microscopy. We have used super
      resolution imaging by direct stochastic optical reconstruction microscopy
      (dSTORM) to investigate the structure of NPCs in isolated Xenopus laevis oocyte
      nuclear envelopes, with a lateral resolution of ~15 nm. By generating accumulated
      super-resolved images of hundreds of NPCs we determined the diameter of the
      central NPC channel to be 41 +/- 7 nm and demonstrate that the integral membrane
      protein gp210 is distributed in an eightfold radial symmetry. Two-color dSTORM
      experiments emphasize the highly symmetric NPCs as ideal model structures to
      control the quality of corrections to chromatic aberration and to test the
      capability and reliability of super-resolution imaging methods.

PMID- 22389395
TI  - Down's-syndrome-related kinase Dyrk1A modulates the p120-catenin-Kaiso trajectory
      of the Wnt signaling pathway.
AB  - The Wnt pathways contribute to many processes in cancer and development, with
      beta-catenin being a key canonical component. p120-catenin, which is structurally
      similar to beta-catenin, regulates the expression of certain Wnt target genes,
      relieving repression conferred by the POZ- and zinc-finger-domain-containing
      transcription factor Kaiso. We have identified the kinase Dyrk1A as a component
      of the p120-catenin-Kaiso trajectory of the Wnt pathway. Using rescue and other
      approaches in Xenopus laevis embryos and mammalian cells, we found that Dyrk1A
      positively and selectively modulates p120-catenin protein levels, thus having an
      impact on p120-catenin and Kaiso (and canonical Wnt) gene targets such as siamois
      and wnt11. The Dyrk1A gene resides within the Down's syndrome critical region,
      which is amplified in Down's syndrome. A consensus Dyrk phosphorylation site in
      p120-catenin was identified, with a mutant mimicking phosphorylation exhibiting
      the predicted enhanced capacity to promote endogenous Wnt-11 and Siamois
      expression, and gastrulation defects. In summary, we report the biochemical and
      functional relationship of Dyrk1A with the p120-catenin-Kaiso signaling
      trajectory, with a linkage to canonical Wnt target genes. Conceivably, this work
      might also prove relevant to understanding the contribution of Dyrk1A dosage
      imbalance in Down's syndrome.

PMID- 22389397
TI  - POLO ensures chromosome bi-orientation by preventing and correcting erroneous
      chromosome-spindle attachments.
AB  - Correct chromosome segregation during cell division requires bi-orientation at
      the mitotic spindle. Cells possess mechanisms to prevent and correct
      inappropriate chromosome attachment. Sister kinetochores assume a 'back-to-back'
      geometry on chromosomes that favors amphitelic orientation but the regulation of
      this process and molecular components are unknown. Abnormal chromosome-spindle
      interactions do occur but are corrected through the activity of Aurora B, which
      destabilizes erroneous attachments. Here, we address the role of Drosophila POLO
      in chromosome-spindle interactions and show that, unlike inhibition of its
      activity, depletion of the protein results in bipolar spindles with most
      chromosomes forming stable attachments with both sister kinetochores bound to
      microtubules from the same pole in a syntelic orientation. This is partly the
      result of impaired localization and activity of Aurora B but also of an altered
      centromere organization with abnormal distribution of centromeric proteins and
      shorter interkinetochore distances. Our results suggests that POLO is required to
      promote amphitelic attachment and chromosome bi-orientation by regulating both
      the activity of the correction mechanism and the architecture of the centromere.

PMID- 22389398
TI  - Giant meiotic spindles in males from Drosophila species with giant sperm tails.
AB  - The spindle is a highly dynamic molecular machine that mediates precise
      chromosome segregation during cell division. Spindle size can vary dramatically,
      not only between species but also between different cells of the same organism.
      However, the reasons for spindle size variability are largely unknown. Here we
      show that variations in spindle size can be linked to a precise developmental
      requirement. Drosophila species have dramatically different sperm flagella that
      range in length from 0.3 mm in D. persimilis to 58.3 mm in D. bifurca. We found
      that males of different species exhibit striking variations in meiotic spindle
      size, which positively correlate with sperm length, with D. bifurca showing 30
      fold larger spindles than D. persimilis. This suggests that primary spermatocytes
      of Drosophila species manufacture and store amounts of tubulin that are
      proportional to the axoneme length and use these tubulin pools for spindle
      assembly. These findings highlight an unsuspected plasticity of the meiotic
      spindle in response to the selective forces controlling sperm length.

PMID- 22389400
TI  - Force transduction and strain dynamics in actin stress fibres in response to
      nanonewton forces.
AB  - It is becoming clear that mechanical stimuli are crucial factors in regulating
      the biology of the cell, but the short-term structural response of a cell to
      mechanical forces remains relatively poorly understood. We mechanically
      stimulated cells transiently expressing actin-EGFP with controlled forces (0-20
      nN) in order to investigate the structural response of the cell. Two clear force
      dependent responses were observed: a short-term (seconds) local deformation of
      actin stress fibres and a long-term (minutes) force-induced remodelling of stress
      fibres at cell edges, far from the point of contact. By photobleaching markers
      along stress fibres we were also able to quantify strain dynamics occurring along
      the fibres throughout the cell. The results reveal that the cell exhibits complex
      heterogeneous negative and positive strain fluctuations along stress fibres in
      resting cells that indicate localized contraction and stretch dynamics. The
      application of mechanical force results in the activation of myosin contractile
      activity reflected in an ~50% increase in strain fluctuations. This approach has
      allowed us to directly observe the activation of myosin in response to mechanical
      force and the effects of cytoskeletal crosslinking on local deformation and
      strain dynamics. The results demonstrate that force application does not result
      in simplistic isotropic deformation of the cytoarchitecture, but rather a complex
      and localized response that is highly dependent on an intact microtubule network.
      Direct visualization of force-propagation and stress fibre strain dynamics have
      revealed several crucial phenomena that take place and ultimately govern the
      downstream response of a cell to a mechanical stimulus.

PMID- 22389399
TI  - Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for
      peroxisome division.
AB  - Peroxisome division is regulated by several factors, termed fission factors, as
      well as the conditions of the cellular environment. Over the past decade, the
      idea of metabolic control of peroxisomal morphogenesis has been postulated, but
      remains largely undefined to date. In the current study, docosahexaenoic acid
      (DHA, C22:6n-3) was identified as an inducer of peroxisome division. In
      fibroblasts isolated from patients that carry defects in peroxisomal fatty acid
      beta-oxidation, peroxisomes are much less abundant than normal cells. Treatment
      of these patient fibroblasts with DHA induced the proliferation of peroxisomes to
      the level seen in normal fibroblasts. DHA-induced peroxisomal proliferation was
      abrogated by treatment with a small inhibitory RNA (siRNA) targeting dynamin-like
      protein 1 and with dynasore, an inhibitor of dynamin-like protein 1, which
      suggested that DHA stimulates peroxisome division. DHA augmented the hyper
      oligomerization of Pex11pbeta and the formation of Pex11pbeta-enriched regions on
      elongated peroxisomes. Time-lapse imaging analysis of peroxisomal morphogenesis
      revealed a sequence of steps involved in peroxisome division, including
      elongation in one direction followed by peroxisomal fission. DHA enhanced
      peroxisomal division in a microtubule-independent manner. These results suggest
      that DHA is a crucial signal for peroxisomal elongation, a prerequisite for
      subsequent fission and peroxisome division.

PMID- 22389401
TI  - AP-1 clathrin adaptor and CG8538/Aftiphilin are involved in Notch signaling
      during eye development in Drosophila melanogaster.
AB  - Clathrin adaptor protein complex-1 (AP-1) and its accessory proteins play a role
      in the sorting of integral membrane proteins at the trans-Golgi network and
      endosomes. Their physiological functions in complex organisms, however, are not
      fully understood. In this study, we found that CG8538p, an uncharacterized
      Drosophila protein, shares significant structural and functional characteristics
      with Aftiphilin, a mammalian AP-1 accessory protein. The Drosophila Aftiphilin
      was shown to interact directly with the ear domain of gamma-adaptin of Drosophila
      AP-1, but not with the GAE domain of Drosophila GGA. In S2 cells, Drosophila
      Aftiphilin and AP-1 formed a complex and colocalized at the Golgi compartment.
      Moreover, tissue-specific depletion of AP-1 or Aftiphilin in the developing eyes
      resulted in a disordered alignment of photoreceptor neurons in larval stage and
      roughened eyes with aberrant ommatidia in adult flies. Furthermore, AP-1-depleted
      photoreceptor neurons showed an intracellular accumulation of a Notch regulator,
      Scabrous, and downregulation of Notch by promoting its degradation in the
      lysosomes. These results suggest that AP-1 and Aftiphilin are cooperatively
      involved in the intracellular trafficking of Notch during eye development in
      Drosophila.

PMID- 22389402
TI  - A functional genetic screen reveals new regulators of beta1-integrin activity.
AB  - beta1 integrins constitute a large group of widely distributed adhesion
      receptors, which regulate the ability of cells to interact with their
      surroundings. This regulation of the expression and activity of integrins is
      crucial for tissue homeostasis and development and contributes to inflammation
      and cancer. We report an RNA interference screen to uncover genes involved in the
      regulation of beta1-integrin activity using cell spot microarray technology in
      cancer cell lines. Altogether, ten cancer and two normal cell lines were used to
      identify regulators of beta1 integrin activity. Cell biological analysis of the
      identified beta1-integrin regulatory genes revealed that modulation of integrin
      activity can influence cell invasion in a three-dimensional matrix. We
      demonstrate with loss-of-function and rescue experiments that CD9 activates and
      MMP8 inactivates beta1 integrins and that both proteins associate with beta1
      integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation
      in vivo. Our discovery of new regulators of beta1-integrin activity highlight the
      complexity of integrin activity regulation and provide a set of new genes
      involved in regulation of integrin function.

PMID- 22389403
TI  - Induction of autophagy in ESCRT mutants is an adaptive response for cell survival
      in C. elegans.
AB  - Endosomes and autophagosomes are two vesicular compartments involved in the
      degradation and recycling of cellular material. They both undergo a maturation
      process and finally fuse with the lysosome. In mammals, the convergence between
      endosomes and autophagosomes is a multistep process that can generate
      intermediate vesicles named amphisomes. Using knockdowns and mutants of the ESCRT
      machinery (ESCRT-0-ESCRT-III, ATPase VPS-4) and the autophagic pathway (LGG-1,
      LGG-2, ATG-7, TOR), we analyzed in vivo the functional links between endosomal
      maturation and autophagy in Caenorhabditis elegans. We report here that, despite
      a strong heterogeneity of their developmental phenotypes, all ESCRT mutants
      present an accumulation of abnormal endosomes and autophagosomes. We show that
      this accumulation of autophagosomes is secondary to the formation of enlarged
      endosomes and is due to the induction of the autophagic flux and not a blockage
      of fusion with lysosomes. We demonstrate that the induction of autophagy is not
      responsible for the lethality of ESCRT mutants but has a protective role on
      cellular degradation. We also show that increasing the basal level of autophagy
      reduces the formation of enlarged endosomes in ESCRT mutants. Together, our data
      indicate that the induction of autophagy is a protective response against the
      formation of an abnormal vesicular compartment.

PMID- 22389404
TI  - CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects
      cell migration.
AB  - Vertebrate gap junctions are composed of proteins from the connexin family. Co
      immunoprecipitation, in vitro binding and far western experiments demonstrate
      that mammalian CASK (also known as LIN2) directly interacts with Cx43.
      Immunoprecipitation studies indicate that the CASK mainly interacts with the
      hypophosphorylated form of Cx43. Functional co-regulation of these proteins was
      found in MDCK cells migrating into a scratch wound, where expression of either
      protein individually inhibits migration but their coexpression abrogates this
      inhibitory effect. Immunofluorescence shows colocalization of Cx43 and CASK in
      mouse brain astrocytes and in response to wounding in human foreskin. During
      wounding, CASK is mobilized to the plasma membrane where it colocalizes with Cx43
      and CADM1 1 hour after skin explant wounding. Together, these studies indicate
      that CASK interaction with Cx43 occurs relatively early in the connexin life
      cycle and imply a plasma membrane targeting role for the interaction that
      apparently affects cellular processes including cellular migration and wound
      healing.

PMID- 22389405
TI  - Differential expression of gastric MUC5AC in colonic epithelial cells: TFF3-wired
      IL1 beta/Akt crosstalk-induced mucosal immune response against Shigella
      dysenteriae infection.
AB  - An understanding of the signaling mechanism(s) that regulate the differential
      expression of gastric mucin MUC5AC in colonic epithelial cells would contribute
      significantly to investigations of its role in colonic mucosa infected with the
      bacterial pathogen Shigella dysenteriae. Here we show that S. dysenteriae
      Sinduced expression of interleukin-1beta upregulates MUC2 expression and the
      differential expression of MUC5AC. Differential expression of MUC5AC involves
      crosstalk between interleukin-1beta and Akt, whereby the trefoil factor family
      peptide TFF3 activates Akt by phosphorylation of EGFR. TFF3 also downregulates E
      cadherin expression, causing accumulation of beta-catenin in the cytosol.
      Phosphorylation of GSK-3beta (inactivated) by activated Akt inhibits
      ubiquitylation of beta-catenin, leading to its nuclear translocation, which then
      induces the expression of MUC5AC and cyclin D1. Accumulation of cyclin D1 alters
      the cell cycle, promoting cell survival and proliferation. Human colon HT29MTX
      cells, which overexpress MUC5AC, were resistant to adherence and invasion of S.
      dysenteriae when compared with other mucin-secreting HT29 cell types. Thus,
      during infection with S. dysenteriae, crosstalk between interleukin-1beta and Akt
      wired by TFF3 induces expression of MUC5AC in colonic epithelial cells.
      Differentially expressed gastric MUC5AC aids in mucosal clearance of S.
      dysenteriae, inhibiting adherence and invasion of the pathogen to colonic
      epithelial cells, which protects the host.

PMID- 22389406
TI  - N-WASP-mediated invadopodium formation is involved in intravasation and lung
      metastasis of mammary tumors.
AB  - Invadopodia are proteolytic membrane protrusions formed by highly invasive cancer
      cells, commonly observed on substrate(s) mimicking extracellular matrix. Although
      invadopodia are proposed to have roles in cancer invasion and metastasis, direct
      evidence has not been available. We previously reported that neural Wiskott
      Aldrich syndrome protein (N-WASP), a member of WASP family proteins that regulate
      reorganization of the actin cytoskeleton, is an essential component of
      invadopodia. Here, we report that N-WASP-mediated invadopodium formation is
      essential in breast cancer invasion, intravasation and lung metastasis. We
      established stable cell lines based on MTLn3 rat mammary adenocarcinoma cells
      that either overexpressed a dominant-negative (DN) N-WASP construct or in which N
      WASP expression was silenced by a pSuper N-WASP shRNA. Both the N-WASP shRNA and
      DN N-WASP cells showed a markedly decreased ability to form invadopodia and
      degrade extracellular matrix. In addition, formation of invadopodia in primary
      tumors and collagen I degradation were reduced in the areas of invasion (collagen
      rich areas in the invasive edge of the tumor) and in the areas of intravasation
      (blood-vessel-rich areas). Our results suggest that tumor cells in vivo that have
      a decreased activity of N-WASP also have a reduced ability to form invadopodia,
      migrate, invade, intravasate and disseminate to lung compared with tumor cells
      with parental N-WASP levels.

PMID- 22389407
TI  - Characterization of dynamic actin associations with T-cell receptor microclusters
      in primary T cells.
AB  - T cell triggering through T-cell antigen receptors (TCRs) results in spatial
      assembly of the receptors on multiple length scales. This assembly is mediated by
      the T cell actin cytoskeleton, which reorganizes in response to TCR
      phosphorylation and then induces the coalescence of TCRs into microclusters,
      followed by their unification into a micrometer-scale structure. The exact
      outcomes of the association of TCRs with a dynamic and fluctuating actin network
      across these length scales are not well characterized, but it is clear that weak
      and transient interactions at the single-molecule level sum to yield significant
      receptor rearrangements at the plasma membrane. We used the hybrid live cell
      nanopatterned supported lipid bilayer system to quantitatively probe the actin
      TCR interaction in primary T cells. A specialized tracking algorithm revealed
      that actin slows as it passes over TCR clusters in a direction-dependent manner
      with respect to the resistance against TCR motion. We also observed transient
      actin enrichments at sites corresponding to putative TCR clusters that far
      exceeded pure stochastic fluctuations and described an image time-autocorrelation
      analysis method to quantify these accumulations.

PMID- 22389408
TI  - Orientation-based FRET sensor for real-time imaging of cellular forces.
AB  - Mechanical stress is an unmapped source of free energy in cells. Mapping the
      stress fields in a heterogeneous time-dependent environment like that found in
      cells requires probes that are specific for different proteins and respond to
      biologically relevant forces with minimal disturbance to the host system. To meet
      these goals, we have designed a genetically encoded stress sensor with minimal
      volume and high sensitivity and dynamic range. The new FRET-based sensor, called
      cpstFRET, is designed to be modulated by the angles between the donor and
      acceptor rather than the distance between them. Relative to other probes, it is
      physically smaller and exhibits a greater dynamic range and sensitivity and
      expresses well. For in vivo testing, we measured stress gradients in time and
      space in non-erythroid spectrin in several different cell types and found that
      spectrin is under constitutive stress in some cells but not in others. Stresses
      appear to be generated by both F-actin and tubulin. The probe revealed, for the
      first time, that spectrin undergoes time-dependent force modulation during cell
      migration. cpstFRET can be employed in vitro, in vivo and in situ, and when
      incorporated into biologically expressed extracellular polymers such as collagen,
      it can report multidimensional stress fields.

PMID- 22389409
TI  - The tumour suppressor Lethal (2) giant discs is required for the function of the
      ESCRT-III component Shrub/CHMP4.
AB  - Recent work indicates that defects in late phases of the endosomal pathway caused
      by loss of function of the tumour suppressor gene lethal (2) giant discs (lgd) or
      the function of the ESCRT complexes I-III result in the ligand-independent
      activation of the Notch pathway in all imaginal disc cells in Drosophila
      melanogaster. lgd encodes a member of an uncharacterised protein family, whose
      members contain one C2 domain and four repeats of the DM14 domain. The function
      of the DM14 domain is unknown. We here report a detailed structure-function
      analysis of Lgd protein, which reveals that the DM14 domains are essential for
      the function of Lgd and act in a redundant manner. Moreover, our analysis
      indicates that the DM14 domain provides the specific function, whereas the C2
      domain is required for the subcellular location of Lgd. We found that Lgd
      interacts directly with the ESCRT-III subunit Shrub through the DM14 domains. The
      interaction is required for the function of Shrub, indicating that Lgd
      contributes to the function of the ESCRT-III complex. Furthermore, our genetic
      studies indicate that the activation of Notch in ESCRT and lgd mutant cells
      occurs in a different manner and that the activity of Shrub and other ESCRT
      components are required for the activation of Notch in lgd mutant cells.

PMID- 22389410
TI  - Regulation of invadopodia formation and activity by CD147.
AB  - A defining feature of malignant tumor progression is cellular penetration through
      the basement membrane and interstitial matrices that separate various cellular
      compartments. Accumulating evidence supports the notion that invasive cells
      employ specialized structures termed invadopodia to breach these structural
      barriers. Invadopodia are actin-based, lipid-raft-enriched membrane protrusions
      containing membrane-type-1 matrix metalloproteinase (MT1-MMP; also known as
      matrix metalloproteinase 14; MMP14) and several signaling proteins. CD147
      (emmprin, basigin), an immunoglobulin superfamily protein that is associated with
      tumor invasion and metastasis, induces the synthesis of various matrix
      metalloproteinases in many systems. In this study we show that upregulation of
      CD147 is sufficient to induce MT1-MMP expression, invasiveness and formation of
      invadopodia-like structures in non-transformed, non-invasive, breast epithelial
      cells. We also demonstrate that CD147 and MT1-MMP are in close proximity within
      these invadopodia-like structures and co-fractionate in membrane compartments
      with the properties of lipid rafts. Moreover, manipulation of CD147 levels in
      invasive breast carcinoma cells causes corresponding changes in MT1-MMP
      expression, invasiveness and invadopodia formation and activity. These findings
      indicate that CD147 regulates invadopodia formation and activity, probably
      through assembly of MT1-MMP-containing complexes within lipid-raft domains of the
      invadopodia.

PMID- 22389411
TI  - Degeneration of retinal layers in multiple sclerosis subtypes quantified by
      optical coherence tomography.
AB  - BACKGROUND: Optical coherence tomography can be used to assess retinal
      degeneration in multiple sclerosis (MS). Thinning of the retinal nerve fibre
      layer and macular thickness have been well characterized, but newer devices allow
      quantification of all retinal layers. OBJECTIVES: The objective of this study was
      to evaluate the thickness of the paramacular retina, peripapillary retinal nerve
      fibre layer, and deeper paramacular layers in MS patient subgroups, using state
      of-the-art optical coherence tomography. METHODS: Using a Heidelberg Engineering
      Spectralis device, we performed paramacular volumetric retinal scans and circular
      peripapillary fibre-layer scans, manually segmenting different retinal layers
      into single horizontal foveal scans in 95 patients with definite MS (42 relapsing
      remitting, 41 secondary progressive, 12 primary progressive), plus 91 age- and
      sex-matched controls. RESULTS: Even without a history of optic neuritis, all MS
      subgroups had significant thinning of the peripapillary retinal nerve fibre
      layer, the paramacular retinal thickness and the retinal ganglion cell- and inner
      plexiform layer. Only in primary progressive MS was the inner nuclear layer
      significantly reduced. CONCLUSIONS: Our findings indicate a primary retinal
      pathology involving the inner nuclear layer in primary progressive MS. Results in
      eyes without history of optic neuritis suggest possible subclinical episodes of
      optic neuritis or retrograde trans-synaptic degeneration of retinal ganglion
      cells and their axons.

PMID- 22389412
TI  - Cognitive reserve in secondary progressive multiple sclerosis.
AB  - BACKGROUND: Consistent with the cognitive reserve hypothesis, lifetime
      intellectual enrichment protects MS patients from cognitive impairment. As
      studies have focused predominately on patients with relapsing-remitting courses,
      it is unknown whether lifetime enrichment is protective against cognitive
      impairment in patients with secondary-progressive MS (SPMS), a more advanced
      disease course. OBJECTIVE: Examine whether greater lifetime intellectual
      enrichment moderates/reduces the deleterious effect of SPMS on memory and
      cognitive efficiency. METHODS: Twenty-five SPMS patients and 25 healthy controls
      (HC) completed neuropsychological tasks, yielding two composite scores: memory
      and cognitive efficiency. An estimate of lifetime enrichment was created from
      educational attainment and vocabulary knowledge. Regression analyses predicted
      memory and cognitive efficiency, with age, sex, intellectual enrichment and group
      (SPMS, HC) controlled in step one, and the interaction between intellectual
      enrichment and group evaluated within step two. RESULTS: Interactions emerged
      between intellectual enrichment and group when predicting memory (R
      (2)Delta=0.081, p = 0.041) and cognitive efficiency (R (2)Delta=0.064, p =
      0.024), such that SPMS patients exhibited deficits relative to HCs at lower
      levels of enrichment, but these SPMS-related cognitive deficits were absent at
      higher levels of enrichment. CONCLUSION: Intellectual enrichment protects SPMS
      patients from cognitive impairment, thereby extending the cognitive reserve
      hypothesis to this more advanced MS disease course.

PMID- 22389413
TI  - MRI-based analysis of the natalizumab therapeutic window in multiple sclerosis.
AB  - The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated
      radiological activity at various times from the last natalizumab infusion by
      examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated
      patients with relapsing-remitting MS. Of 113 scans performed >4 weeks after last
      natalizumab infusion, 26 were active (i.e. had >=1 contrast-enhancing lesions).
      Risk of radiological activity increased by 1.34 fold for each week of delay with
      respect to the recommended 4-week dosing interval, compared with schedule
      adherent patients (p<0.0001). Our data suggest that an increased MRI activity >=7
      weeks from the last infusion of natalizumab should be considered in cases of
      therapy discontinuation.

PMID- 22389414
TI  - The relation between cognitive and motor dysfunction and motor imagery ability in
      patients with multiple sclerosis.
AB  - BACKGROUND: Motor imagery (MI) was recently shown to be a promising tool in
      neurorehabilitation. The ability to perform MI, however, may be impaired in some
      patients with neurological dysfunction. OBJECTIVE: The objective was to assess
      the relation between cognitive and motor dysfunction and MI ability in patients
      with multiple sclerosis (MS). METHODS: Thirty patients with MS underwent
      cognitive and motor screening, and also performed a composite test battery to
      assess their MI ability. This test battery consisted of a questionnaire, a hand
      rotation task and a test based on mental chronometry. Patients' MI ability was
      compared with the MI ability of age-matched healthy controls. Moreover, their MI
      scores were compared between body sides and were correlated with their scores on
      tests of motor and cognitive functioning. RESULTS: The average accuracy and
      temporal organization of MI significantly differed between MS patients and
      controls. Patients' MI accuracy significantly correlated with impairments in
      cognitive functioning, but was independent of motor functioning. MI duration, on
      the other hand, was independent of cognitive performance, but differed between
      the patients' most and least affected side. CONCLUSION: These findings are of use
      when considering the application of MI practice in MS patients' rehabilitation.

PMID- 22389415
TI  - Abnormal cervical cord function contributes to fatigue in multiple sclerosis.
AB  - BACKGROUND/OBJECTIVE  We aimed to investigate whether cervical cord damage and
      dysfunction is associated with the presence and severity of fatigue in multiple
      sclerosis (MS) using a multiparametric magnetic resonance (MR) approach. METHODS:
      Cervical cord functional magnetic resonance imaging (fMRI) during a tactile
      stimulation of the right hand, and structural brain and cord MRI were acquired
      from 20 controls, 15 MS patients without fatigue (NF) and 20 MS patients with
      fatigue (F). Between-group differences in the extent of focal lesions and
      diffusivity abnormalities in the brain and cord, cord-normalized cross-sectional
      area (CSAn) and fMRI activity were assessed. RESULTS: All structural MRI measures
      differed significantly among groups, except for cord lesion number and CSAn.
      Compared with controls, NF-MS patients experienced higher cord recruitment
      (p=0.04). Compared with F-MS, NF-MS patients had a lower brain normal-appearing
      white matter average fractional anisotropy (p=0.001) and increased cord
      recruitment (p=0.02). In patients with MS, the extent of cord recruitment was
      correlated with the severity of fatigue (r=-0.34, p=0.04). Compared with the
      other two groups, F-MS patients had a more diffuse recruitment of cord quadrants
      on the axial and longitudinal planes. CONCLUSIONS: Abnormalities of function, but
      not of structure, of the cervical cord are likely to contribute to the
      pathogenesis of fatigue in MS.

PMID- 22389417
TI  - Implantable cardioverter defibrillator harm?
AB  - Despite the general acceptance of implantable cardioverter defibrillator (ICD)
      therapy [including cardiac resynchronization therapy defibrillator (CRT-D)] among
      cardiologists, there has been some recent concern about potential harm associated
      with ICDs, particularly related to quality of life and possible adverse effects
      of ICD shocks. These and others undeniably constitute complications of ICD
      therapy paper. However, the evidence from multiple ICD/CRT-D trials, which take
      into account complications on the one side, and benefits on the other, speaks
      strongly in favour of patients receiving net benefit, rather than harm. And this
      is true for (i) prognosis, (ii) effects of shocks, and (iii) quality of life.
      Moreover--addressing specifically the complications aspects--there have been
      major advances, both in the technology of the systems and in physician practice,
      which have put major focus on minimizing shocks (appropriate and inappropriate)
      in favour of antitachycardia pacing. In addition, the tendency is that more and
      more of such patients receive devices incorporating cardiac resynchronization
      pacing, now proven to delay and/or minimize heart failure. There is now a large
      body of evidence, particularly in recent years with improved technology, that,
      rather than 'harm', the ICD/CRT-D provides substantial protection for
      appropriately selected patients.

PMID- 22389416
TI  - Long-term follow-up on high-rate cut-off programming for implantable cardioverter
      defibrillators in primary prevention patients with left ventricular systolic
      dysfunction.
AB  - AIMS: Implantable cardioverter defibrillators (ICDs) are efficient in reducing
      mortality in patients with left ventricular systolic dysfunction. High-rate cut
      off programming may be effective in reducing appropriate and inappropriate
      therapies, but as the long-term consequences on morbidity and mortality remain
      unclear, it is underutilized. METHODS AND RESULTS: We prospectively studied 365
      consecutive patients (mean age 60 +/- 10 years), with ischaemic (63%) or non
      ischaemic cardiomyopathy and left ventricular dysfunction (mean ejection fraction
      25 +/- 7%), who were implanted with an ICD in primary prevention of sudden
      cardiac death (41% single chamber, 31% dual chamber, and 28% biventricular). All
      devices were programmed with a shock-only zone over 220 beats per minute (b.p.m.)
      and a monitoring zone between 170 and 220 b.p.m. During a median follow-up of 40
      months, 41 patients received appropriate shocks (11.2%) and 24 inappropriate
      shocks (6.6%). Then, 306 patients never experienced any ICD shock (84%).
      Inappropriate discharges were related to supraventricular tachyarrhythmia in 10
      patients, and noise/oversensing in 14 patients. Ventricular tachycardia episodes,
      sustained or not, were recorded in the monitoring zone in 43 patients (11.8%).
      Seven of these patients were symptomatic (1.9%), without lethal consequence.
      Sixty-two patients (17%) died: 35 from end-stage heart failure, 1 from
      unexplained sudden death, and 26 from a documented non-cardiac cause. CONCLUSION:
      High-rate cut-off (220 b.p.m.) shock-only ICD programming, in primary prevention
      patients with reduced left ventricular ejection fraction, appeared to be safe
      during a long-term follow-up. It also resulted in a very low rate of discharges,
      which are known to be deleterious in this population.

PMID- 22389418
TI  - In-hospital monitoring of T-wave alternans in a case of amiodarone-induced
      torsade de pointes: clinical and methodologic insights.
AB  - We report a case of macroscopic T-wave alternans occurring 30 min before the
      onset of amiodarone-induced torsade de pointes, illustrating a means to monitor
      for proarrhythmia.

PMID- 22389419
TI  - Pacemaker therapy: the newborn and the nonagenarian.

PMID- 22389420
TI  - Introduction of new industry standards for cardiac implantable electronic
      devices: balancing benefits and unexpected risks.
AB  - The DF-4 connector is a novel industry standard for the connection of a
      defibrillator lead to the generator. It aims at reducing the bulk created by two
      or three pins at the proximal end of the defibrillator lead and its corresponding
      ports at the header of the device. Having only one connection port between the
      lead and the device reduces the material in the pocket, the risk of lead-to-port
      mismatch, may lower the risk of lead abrasion, and probably makes the
      implantation procedure a little easier since only one set screw is required.
      However, all these conceived benefits are related to convenience rather than to a
      medical need. After the recent experiences with the possible negative clinical
      impact of 'minor' changes like simply downsizing a defibrillator lead, a word of
      caution is warranted. The lead is the weakest part of the defibrillator system,
      complex in design and undergoing constant stress through movement. It is very
      hard to predict which issues may evolve over time with the changes in lead
      design. Does the perceived benefit really outweigh an unpredictable risk in a
      sensitive medical product like a defibrillator? This article tries to address the
      possible issues of the new spring contacts instead of set screws, the proximity
      of the low- and high-voltage connections as well as the inability of adding a
      pace/sense or an additional shock lead without a special adaptor, and advocates a
      measured speed in the introduction of this technology.

PMID- 22389421
TI  - Successful laser lead extraction through a stented baffle in a patient with
      surgically corrected D-transposition.

PMID- 22389422
TI  - 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation
      of Atrial Fibrillation: recommendations for patient selection, procedural
      techniques, patient management and follow-up, definitions, endpoints, and
      research trial design.

PMID- 22389423
TI  - The effects of transverse rotation angle on compression and effective lever arm
      of prosthetic feet during simulated stance.
AB  - BACKGROUND AND AIM: Unlike sagittal plane prosthesis alignment, few studies have
      observed the effects of transverse plane alignment on gait and prosthesis
      behaviour. Changes in transverse plane rotation angle will rotate the points of
      loading on the prosthesis during stance and may alter its mechanical behaviour.
      This study observed the effects of increasing the external transverse plane
      rotation angle, or toe-out, on foot compression and effective lever arm of three
      commonly prescribed prosthetic feet. TECHNIQUE: The roll-over shape of a SACH,
      Flex and single-axis foot was measured at four external rotation angle conditions
      (0 degrees , 5 degrees , 7 degrees  and 12 degrees  relative to neutral).
      Differences in foot compression between conditions were measured as average
      distance between roll-over shapes. DISCUSSION: Increasing the transverse plane
      rotation angle did not affect foot compression. However, it did affect the
      effective lever arm, which was maximized with the 5 degrees  condition, although
      differences between conditions were small. CLINICAL RELEVANCE: Increasing the
      transverse plane rotation angle of prosthetic feet by up to 12 degrees  beyond
      neutral has minimal effects on their mechanical behaviour in the plane of walking
      progression during weight-bearing.

PMID- 22389424
TI  - Selecting a test for the clinical assessment of balance and walking capacity at
      the definitive fitting state after unilateral amputation: a comparative study.
AB  - BACKGROUND: There is a lack of data and consensus concerning the most appropriate
      functional evaluation in clinical practice at the definitive prosthetic phase
      after lower limb amputation. OBJECTIVES: To determine among several selected
      functional tests the most pertinent to evaluate balance and prosthetic walking.
      STUDY DESIGN: Validation of a diagnostic procedure. METHODS: Sixty-four patients
      were included. OUTCOME MEASURES: Timed Up and Go test, Functional Reach test
      (FRT), one-leg balance, tandem test, Modified Houghton Scale, Berg Balance Scale,
      two-minute walk test (2MW test). Correlations were assessed with the Pearson
      correlation coefficient and the Principal Component Analysis. Score distribution
      was analyzed with the Shapiro-Wilk W normality test. Receiver operating
      characteristic curves were drawn to identify the best predictor for the function.
      RESULTS: The clinical tests correlated highly with each other. Only 2MW test and
      FRT did not have either a floor/ceiling effect, or a bi-modal distribution. The
      2MW test was the best predictor of prosthetic walking limitations (area under the
      curve 0.93 (0.83-0.97), the best threshold was between 130 and 150 meters), and
      FRT was best for balance. CONCLUSIONS: 2MW test can be proposed as the first-line
      clinical test. The FRT can be indicated for the specific assessment of balance
      disorders. Clinical relevance This validation of a clinical evaluation of balance
      and walking capacity after lower limb amputation may be useful in everyday
      practice to ensure in a simple and standardized way the follow-up of patients and
      adapt treatments--especially prosthetics--at the definitive prosthetic phase.

PMID- 22389425
TI  - In vivo kinetics of indoxyl sulfate in humans and its renal interaction with
      angiotensin-converting enzyme inhibitor quinapril in rats.
AB  - Indoxyl sulfate (IS) is an organic anion uremic toxin that accumulates in
      patients with chronic kidney disease (CKD). The aims of this study were to
      examine the kinetic profiles of IS in humans at a steady state after multiple
      doses of L-Trp, a precursor of IS, and the in vivo interaction of IS with the
      angiotensin-converting enzyme inhibitor quinapril, whose active metabolite is a
      substrate of organic anion transporter 3 (OAT3) in rats. First, 12-h kinetics
      after single doses of Trp (2, 4, and 8 g) were examined in two healthy
      volunteers. Second, 24-h kinetics after a single dose of 2 g of Trp was studied
      in six volunteers. Third, 35-h kinetics after single and multiple doses of 2 g of
      Trp were examined in five volunteers. In anesthetized rats, quinapril or
      probenecid, an inhibitor of OATs, was given intravenously before IS, and blood
      and urine samples were taken until 90 min. Trp and IS concentrations were
      determined by high-performance liquid chromatography. Ultrafiltration was used to
      measure serum unbound IS concentrations. Renal tubular secretion of IS accounted
      for more than 90% of its renal clearance in the steady state of serum IS levels
      after multiple doses in humans. In animals, the serum area under the curve of IS
      increased in conjunction with a decrease in renal clearances after
      coadministration of IS with quinapril or probenecid. It is concluded that
      quinapril may inhibit the urine excretion of IS via OAT3-mediated renal tubular
      transport in patients with CKD.

PMID- 22389427
TI  - Treatment of acute rhinosinusitis: discrepancy between guideline recommendations
      and clinical practice.
AB  - BACKGROUND: A revised primary care guideline on acute rhinosinusitis (ARS) has
      been introduced in the Netherlands in 2005, which advocates a more judicious use
      of antibiotics. OBJECTIVE: To investigate whether consultation and prescription
      rates for ARS in adults changed over recent years in order to provide information
      on family physicians' behaviour before and after introduction of the revised
      guideline. METHODS: Retrospective cohort study. All adult patients within the
      computerized database of Utrecht Primary Care Research Network over the years
      2000-09 were included. Clinical diagnoses of ARS were recorded according to the
      International Classification of Primary Care codes (R75 and/or R09) and drug
      prescriptions according to the Anatomical Therapeutic Chemical Classification
      System. RESULTS: ARS consultation rates revealed a stable pattern, with an
      average consultation rate of 29 episodes per 1000 person-years. From 2000 to
      2005, the antibiotic prescription rate increased from 56 to 62 prescriptions per
      100 episodes (P value for time trend <0.05). From 2005 onwards, the antibiotic
      prescription rate decreased to 56 per 100 episodes in 2009 [rate difference (RD):
      -6, 95% confidence interval (CI): -10 to -1; P value for difference between 2000
      05 and 2005-09 <0.05]. From 2005 to 2009, intranasal corticosteroid (INCS)
      prescription rate increased from 20 to 31 prescriptions per 100 episodes (RD: 11,
      95% CI: 7 to 15; P value for difference between 2000-05 and 2005-09 <0.01). Oral
      corticosteroid prescription and referral rates remained low. CONCLUSIONS: Despite
      strong guideline recommendations to restrict the use of antibiotics and INCS, we
      found only a modest decrease in antibiotic prescription rates, whereas INCS
      prescription rates even increased.

PMID- 22389426
TI  - Pituitary adenylate cyclase-activating polypeptide causes tyrosine
      phosphorylation of the epidermal growth factor receptor in lung cancer cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an autocrine growth
      factor for some lung cancer cells. The activated PACAP receptor (PAC1) causes
      phosphatidylinositol turnover, elevates cAMP, and increases the proliferation of
      lung cancer cells. PAC1 and epidermal growth factor receptor (EGFR) are present
      in non-small-cell lung cancer (NSCLC) cells, and the growth of NSCLC cells is
      inhibited by the PAC1 antagonist PACAP(6-38) and the EGFR tyrosine kinase
      inhibitor gefitinib. Here, the ability of PACAP to transactivate the EGFR was
      investigated. Western blot analysis indicated that the addition of PACAP but not
      the structurally related vasoactive intestinal peptide increased EGFR tyrosine
      phosphorylation in NCI-H838 or H345 cells. PACAP-27, in a concentration-dependent
      manner, increased EGFR transactivation 4-fold 2 min after addition to NCI-H838
      cells. The ability of 100 nM PACAP-27 to increase EGFR or extracellular signal
      regulated kinase tyrosine phosphorylation in NCI-H838 cells was inhibited by
      PACAP(6-38), gefitinib, 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4
      d]pyrimidine (PP2; Src inhibitor), (R)-N4-hydroxy-N1-[(S)-2-(1H-indol-3-yl)-1
      methylcarbamoyl-ethyl]-2-isobutyl-succinamide (GM6001; matrix metalloprotease
      inhibitor), or antibody to transforming growth factor alpha (TGFalpha). By enzyme
      linked immunosorbent assay, PACAP addition to NCI-H838 cells increased TGFalpha
      secretion into conditioned media. EGFR transactivation caused by the addition of
      PACAP to NCI-H838 cells was inhibited by N-acetyl-cysteine (antioxidant), tiron
      (superoxide scavenger), diphenylene iodonium (NADPH oxidase inhibitor), or 1-[6
      [[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione
      (U73122; phospholipase C inhibitor), but not N-[2-[[3-(4-bromophenyl)-2
      propenyl]amino]ethyl]-5-isoquinolinesulfonamide (H89; protein kinase A
      inhibitor). PACAP addition to NCI-H838 cells significantly increased reactive
      oxygen species, and the increase was inhibited by tiron. The results indicate
      that PACAP causes transactivation of the EGFR in NSCLC cells in an oxygen
      dependent manner that involves phospholipase C but not protein kinase A.

PMID- 22389428
TI  - Rimonabant improves obesity but not the overall cardiovascular risk and quality
      of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by
      Rimonabant: the Effectiveness in Daily practice and its USE).
AB  - BACKGROUND: Rimonabant treatment, examined in Phase 3 trials, showed improvement
      of cardiovascular risk factors in obese patients. OBJECTIVE: The objective of
      this Phase 4 trial is to assess the effectiveness of rimonabant plus lifestyle
      counselling when used in daily practice, namely in the general practice. The
      hypothesis was that the effectiveness in Phase 4 would be smaller than the
      efficacy in Phase 3 due to different patient selection and treatment conditions.
      At the end of this trial, rimonabant was suspended of all markets due to
      psychiatric side effects. METHODS: This trial randomly assigned 222 patients with
      enlarged waist circumferences and hyperglycaemia or diabetes mellitus type 2,
      recruited from Dutch general practices, to double-blinded therapy with either
      placebo or rimonabant (20 mg/day) for 1 year in addition to lifestyle
      counselling. RESULTS: Compared with placebo, the rimonabant group showed
      significant improvements in body weight, body mass index, high-density
      lipoprotein (HDL) cholesterol and the main outcome waist circumference after 1
      year. The United Kingdom Prospective Diabetes Study risk calculation showed no
      significant difference. The rimonabant group showed statistically deterioration,
      compared with the placebo group, in the quality of life in the EuroQol and two
      domains of the SF-36: role limitations due to physical health problems and bodily
      pain. CONCLUSIONS: The unique real life data of this Phase 4 trial showed that
      the effectiveness of rimonabant in daily practice is indeed lower than in
      controlled circumstances (Phase 3). Rimonabant treatment showed improvement of
      obesity and the HDL cholesterol, but had no positive effect on the other
      cardiovascular risk factors and the quality of life.

PMID- 22389429
TI  - Health planning for the future: comparative risk assessment of five major
      lifestyle risk factors: evidence from the Wirral, UK.
AB  - BACKGROUND: The aim of this study was to quantify and compare the burden of
      disease attributable to five major lifestyle-related risk factors in a UK Primary
      Care Trust (Wirral) using World Health Organizations' (WHO) comparative risk
      assessment (CRA) methodology to demonstrate its practical utility for informing
      local policy initiatives. METHODS: WHO CRA methodology was adopted using exposure
      data from a local lifestyle survey, disease risk factor relationships published
      by the WHO and local mortality data to calculate risk factor attributable deaths
      and years of life lost (YLL). RESULTS: Smoking remains by far the leading cause
      of deaths followed by overweight and obesity and low fruit and vegetable intake.
      Alcohol ranked last by number of deaths, but second by YLL indicating its high
      contribution to deaths at younger ages. CONCLUSIONS: We have demonstrated the
      utility of WHO CRA methodology to influence health-related policy-making at a
      local level. Primary prevention should remain high on the agenda of government
      initiatives to reduce the future burden of ill health. Future research in this
      area could look at more in-depth national data to cover a wider range of risk
      factors addressing some of the methodological and data shortcomings identified in
      this study.

PMID- 22389430
TI  - Who gets mental health treatment from the GP? Results from the Israel National
      Epidemiological Mental Health Survey.
AB  - BACKGROUND: In view of the pending mental health (MH) reform, an increase in
      demand of MH services is expected. Primary care physicians will presumably be
      involved in meeting this expected increased demand. OBJECTIVES: To identify the
      preferable route of service use of populations with MH problems based on data
      from the Israel National Health Survey (INHS). METHODS: The sample was drawn from
      the INHS which assessed mental disorders as well as the existence of chronic
      physical diseases in the population and the use of services for MH problems
      (specialty and primary care). The examined variables were (i) the existence of
      any mood or anxiety disorder and its severity, (ii) suffering from a chronic
      physical disease, (iii) use of MH services and (iv) use of general health
      services for MH problems. RESULTS: Fifty-one per cent of all those treated for MH
      problems were treated in the MH specialty sector and 49% in the general sector.
      Among those who met the diagnostic Composite International Diagnostic Interview
      criteria of any mood or anxiety disorder, the percentages were 62% and 38%,
      respectively. Irrespective of diagnosis, the proportion of those using the
      services of the GP is significantly greater among people above the age 50 years
      than among younger people. CONCLUSIONS: People with emotional problems above the
      age of 50 years are more likely to prefer help for their problems from their GP
      regardless of the presence of any mental disorder or of a chronic medical
      disease.

PMID- 22389431
TI  - Selective exposure in decided and undecided individuals: differential relations
      to automatic associations and conscious beliefs.
AB  - People often show a preference for information that confirms their attitudes and
      beliefs, and this tendency is reduced for opinions that are not held with
      conviction. The present study shows that both decided and undecided individuals
      show a tendency to selectively expose themselves to confirmatory information,
      albeit with different antecedents and consequences. Whereas selective exposure in
      decided participants was predicted by conscious beliefs and not by automatic
      associations, selective exposure in undecided participants was predicted by
      automatic associations and not by conscious beliefs. Moreover, selective exposure
      led undecided participants to adopt conscious beliefs that were in line with
      their preexisting automatic associations. Conversely, for decided participants,
      selective exposure shifted automatic associations in a direction that was in line
      with their preexisting conscious beliefs. Implications for decision making and
      mutual influences of automatic associations and conscious beliefs in attitude
      change are discussed.

PMID- 22389432
TI  - Suppression sours sacrifice: emotional and relational costs of suppressing
      emotions in romantic relationships.
AB  - What happens when people suppress their emotions when they sacrifice for a
      romantic partner? This multimethod study investigates how suppressing emotions
      during sacrifice shapes affective and relationship outcomes. In Part 1, dating
      couples came into the laboratory to discuss important romantic relationship
      sacrifices. Suppressing emotions was associated with emotional costs for the
      partner discussing his or her sacrifice. In Part 2, couples participated in a 14
      day daily experience study. Within-person increases in emotional suppression
      during daily sacrifice were associated with decreases in emotional well-being and
      relationship quality as reported by both members of romantic dyads. In Part 3,
      suppression predicted decreases in relationship satisfaction and increases in
      thoughts about breaking up with a romantic partner 3 months later. In the first
      two parts of the study, authenticity mediated the costly effects of suppression.
      Implications for research on close relationships and emotion regulation are
      discussed.

PMID- 22389433
TI  - The role of structural disorder in the rewiring of protein interactions through
      evolution.
AB  - Structurally disordered regions play a key role in protein-protein interaction
      networks and the evolution of highly connected proteins, enabling the molecular
      mechanisms for multiple binding. However, the role of protein disorder in the
      evolution of interaction networks has only been investigated through the analysis
      of individual proteins, making it impossible to distinguish its specific impact
      in the (re)shaping of their interaction environments. Now, the availability of
      large interactomes for several model organisms permits exploration of the role of
      disorder in protein interaction networks not only at the level of the interacting
      proteins but of the interactions themselves. By comparing the interactomes of
      human, fly, and yeast, we discovered that, despite being much more abundant,
      disordered interactions are significantly less conserved than their ordered
      counterparts. Furthermore, our analyses provide evidence that this happens not
      only because disordered proteins are less conserved but also because they display
      a higher capacity to rewire their interaction neighborhood through evolution.
      Overall, our results support the hypothesis that conservation of disorder gives a
      clear evolutionary advantage, facilitating the change of interaction partners
      during evolution. Moreover, this mechanism is not exclusive of a few anecdotal
      cases but a global feature present in the interactome networks of entire
      organisms.

PMID- 22389434
TI  - Assembly and insertion of a self-fitting hearing aid: design of effective
      instruction materials.
AB  - A self-fitting hearing aid has been proposed as a viable option to meet the need
      for rehabilitation in areas where audiology services are unreliable. A successful
      outcome with a self-fitting hearing aid pivots in part on the clarity of the
      instructions accompanying the device. The aims of this article are (a) to review
      the literature to determine features that should be incorporated into written
      health-care materials and factors to consider in the design process when
      developing written instructions for a target audience of older adults and (b) to
      apply this information to the development of a set of written instructions as the
      first step in self-fitting of a hearing aid, assembling four parts and inserting
      the aid into the ear. The method involved a literature review of published peer
      reviewed research. The literature revealed four steps in the development of
      written health-care materials: planning, design, assessment of suitability, and
      pilot testing. Best practice design principles for each step were applied in the
      development of instructions for how to assemble and insert a hearing aid.
      Separate booklets were developed for the left and right aids and the content of
      each consisted of simple line drawings accompanied by captions. The reading level
      was Grade 3.5 equivalent and the Flesch Reading Ease Score was 91.1 indicating
      that the materials were "very easy" to read. It is essential to follow best
      practice design principles when developing written health-care materials to
      motivate the reader, maximize comprehension, and increase the likelihood of
      successful application of the content.

PMID- 22389435
TI  - Lysine succinylation and lysine malonylation in histones.
AB  - Histone protein post-translational modifications (PTMs) are significant for gene
      expression and DNA repair. Here we report the identification and validation of a
      new type of PTM in histones, lysine succinylation. The identified lysine
      succinylated histone peptides were verified by MS/MS of synthetic peptides, HPLC
      co-elution, and isotopic labeling. We identified 13, 7, 10, and 7 histone lysine
      succinylation sites in HeLa, mouse embryonic fibroblast, Drosophila S2, and
      Saccharomyces cerevisiae cells, respectively. We demonstrated that this histone
      PTM is present in all eukaryotic cells we examined. Mutagenesis of succinylation
      sites followed by functional assays implied that histone lysine succinylation can
      cause unique functional consequences. We also identified one and two histone
      lysine malonylation sites in HeLa and S. cerevisiae cells, respectively. Our
      results therefore increase potential combinatorial diversity of histone PTMs and
      suggest possible new connections between histone biology and metabolism.

PMID- 22389436
TI  - Metformin and cancer stem cells: old drug, new targets.
AB  - In this issue of the journal, Bao and colleagues report (beginning on page 355)
      that the antidiabetic drug metformin targets pancreatic cancer stem cells
      through, at least partially, the modulation of miRNA expression and subsequent
      regulation of stem cell renewal and signaling factors. In this Perspective, we
      briefly discuss the cancer stem cell hypothesis, its clinical relevance, and how
      targeting the mTOR pathway may yield an avenue for disrupting the cancer stem
      cell compartment and thus yield long-term therapeutic benefit in multiple
      cancers.

PMID- 22389437
TI  - Functional protein pathway activation mapping of the progression of normal skin
      to squamous cell carcinoma.
AB  - Reverse phase protein microarray analysis was used to identify cell signaling
      derangements in squamous cell carcinoma (SCC) compared with actinic keratosis
      (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with
      isolation and enrichment of epithelial cells by laser capture microdissection.
      Set 1 served as a pilot and a means to identify protein pathway activation
      alterations that could be further validated in a second independent set. Set 1
      was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20
      UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis,
      were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein
      (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC
      compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and
      mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical
      clustering revealed that AK and UIA shared a common signaling network activation
      architecture while SCC was dramatically different. Statistical analysis found
      that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as
      increased Bax and Bak expression was higher in AK compared with UIA. We expanded
      pathway network activation mapping in set 2 to 101 key signaling proteins, which
      corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of
      a number of upstream and downstream signaling molecules within these pathways to
      conclude that SCC is indeed a pathway activation-driven disease. Pathway
      activation mapping of SCC compared with AK revealed several interconnected
      networks that could be targeted with drug therapy for potential chemoprevention
      and therapeutic applications.

PMID- 22389438
TI  - Class I histone deacetylases localize to the endoplasmic reticulum and modulate
      the unfolded protein response.
AB  - Post-translational modification through protein acetylation is emerging as an
      important mode of cellular regulation. We have previously demonstrated the role
      that glucose-regulated protein 78 kDa (GRP78) acetylation and subsequent
      activation of the unfolded protein response (UPR) play in the antitumor activity
      of class I histone deacetylase (HDAC) inhibitors, which primarily target class I
      HDACs. In this study, we explored the contributory role these class I HDACs may
      play in UPR regulation. Binding studies were performed using
      immunoprecipitation/immunoblotting following dual-transfection with HA-tagged
      GRP78 and FLAG-tagged HDACs. Subcellular localization was performed using Western
      blot of fractionated cell lysates and confocal microscopy. Individual HDACs were
      inhibited using RNA interference. We identified the potential of HDACs 1, 2, and
      3 to bind to GRP78. These HDACs colocalized with GRP78 in the endoplasmic
      reticulum (ER). Inhibition of individual HDACs resulted in GRP78 acetylation and
      selective activation of the UPR. Although traditionally viewed as nuclear
      enzymes, we demonstrate that Class I HDACs localize to the ER, bind to GRP78, and
      selectively activate the UPR, representing a novel mode of UPR regulation and
      mechanism of action of HDAC inhibitors.

PMID- 22389439
TI  - The cellular apoptosis susceptibility CAS/CSE1L gene protects ovarian cancer
      cells from death by suppressing RASSF1C.
AB  - The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in cancer,
      although it was originally identified as a gene that renders cells vulnerable to
      apoptotic stimuli. CAS/CSE1L has roles in the nucleocytoplasmic recycling of
      importin-alpha and in the regulation of gene expression, cell migration, and
      secretion. We identified CAS/CSE1L as a survival factor for ovarian cancer cells
      in vitro and in vivo. In 3/3 ovarian cancer cell lines, CAS/CSE1L was down
      modulated by the unorthodox proapoptotic signaling of the MET receptor. CAS/CSE1L
      knockdown with RNA interference committed the ovarian cancer cells to death, but
      not immortalized normal cells and breast and colon cancer cells. In 70 and 95% of
      these latter cells, respectively, CAS/CSE1L was localized in the cytoplasm, while
      it accumulated in the nucleus in >90% of ovarian cancer cells. Nuclear
      localization depended on AKT, which was constitutively active in ovarian cancer
      cells. In the nucleus, CAS/CSE1L regulated the expression of the proapoptotic Ras
      association domain family 1 gene products RASSF1C and RASSF1A, which mediated
      death signals evoked by depletion of CAS/CSE1L. Our data show that CAS/CSE1L
      protects ovarian cancer cells from death through transcriptional suppression of a
      proapoptotic gene and suggest that the localization of CAS/CSE1L dictates its
      function.

PMID- 22389440
TI  - A model for the role of isomerization in nascent peptide movement through the
      ribosomal tunnel.
AB  - The ribosome is a molecular machine whose manner of controlling the progression
      of the nascent chain through the ribosomal exit tunnel is currently unknown. A
      novel model for the mechanism driving the nascent chain motion is hereby
      presented, in which the ~180 degrees  rotatory motion performed by each C
      terminal amino acid of the nascent chain during its translocation from the A site
      to the P site, is suggested to twist the newly formed peptide bond into cis
      conformation. By catalyzing the cis to trans isomerization, the ribosome is
      proposed to release the potential energy stored within the cis conformer and to
      utilize it to push the chain down the tunnel, thus operating as a molecular
      motor. This hypothetical isomerization mechanism is supported by its ability to
      provide an explanation for the peculiar conduct observed in translational events
      of nascent chains with C-terminal prolines: the slow peptide bond formation with
      puromycin, translation arrest, and tmRNA tagging.

PMID- 22389441
TI  - Visualization by mass spectrometry of 2-dimensional changes in rat brain lipids,
      including N-acylphosphatidylethanolamines, during neonatal brain ischemia.
AB  - Spatial synthesis of N-acyl-phosphatidylethanolamines (NAPEs) and N
      acylethanolamines (NAEs) during ischemia-reperfusion in neonatal rats has been
      investigated and compared to the spatial degradation of other phospholipids.
      Ischemia was induced in anesthetized Wistar P7 rat pups by left middle cerebral
      artery electrocoagulation combined with a transient and concomitant occlusion of
      both common carotid arteries. Pups were sacrificed after 24 and 48 h. Sham
      treated animals were sacrificed after 48 h. The frozen brains were sliced and
      subjected to desorption electrospray ionization imaging mass spectrometry. There
      was a remarkable increase in the levels of many species of NAPEs in the whole
      injured area at both time points, and a clear but minor increase in selected
      NAEs. In the ischemic area, the sodium adducts of phosphatidylcholine and of lyso
      phosphatidylcholine accumulated and the potassium adduct of phosphatidylcholine
      disappeared, indicating breakdown of the Na(+)/K(+) pump. Free fatty acids, e.g.,
      arachidonic and docosahexaenoic acids, tended to be more abundant in the
      periphery than in the center of the ischemic area and showed different spatial
      distribution. NAPEs are synthesized in the whole ischemic area where the cells
      seem to be dead and other phospholipids are degraded. Free fatty acids can be
      found in the periphery of the ischemic area.

PMID- 22389442
TI  - Manic depression in literature: the case of Virginia Woolf.
AB  - The steady growth of the discipline of medical humanities has facilitated better
      understanding of the symptoms and signs of mental health conditions and the
      feelings of the humans experiencing them. In this project, the arts have been
      seen as enabling re-engagement of the practitioner with the patient's own
      perceptions and feelings. With respect to the association between creativity and
      bipolar disorder in particular, work within medical humanities has meant that
      mentally ill creative individuals have been subject to scientific scrutiny and
      investigation, rather than continuing to be viewed as naively romanticised cases
      of mental illness. This paper is an attempt to supplement traditional literary
      criticism by examining Virginia Woolf's history of bipolar disorder through a
      medical humanities lens. I will provide an overview of Woolf's history of manic
      depressive episodes, their symptoms and manifestation, look back on her
      circumstances during their occurrence, and observe the author's losing battle to
      salvage her identity in the throes of the disease. The aim is to offer further
      insight into Woolf's psychopathology and to gain some understanding of the causes
      and progression of the condition that led to her death by suicide.

PMID- 22389443
TI  - Phylogenetic signal and noise: predicting the power of a data set to resolve
      phylogeny.
AB  - A principal objective for phylogenetic experimental design is to predict the
      power of a data set to resolve nodes in a phylogenetic tree. However, proactively
      assessing the potential for phylogenetic noise compared with signal in a
      candidate data set has been a formidable challenge. Understanding the impact of
      collection of additional sequence data to resolve recalcitrant internodes at
      diverse historical times will facilitate increasingly accurate and cost-effective
      phylogenetic research. Here, we derive theory based on the fundamental unit of
      the phylogenetic tree, the quartet, that applies estimates of the state space and
      the rates of evolution of characters in a data set to predict phylogenetic signal
      and phylogenetic noise and therefore to predict the power to resolve internodes.
      We develop and implement a Monte Carlo approach to estimating power to resolve as
      well as deriving a nearly equivalent faster deterministic calculation. These
      approaches are applied to describe the distribution of potential signal,
      polytomy, or noise for two example data sets, one recent (cytochrome c oxidase I
      and 28S ribosomal rRNA sequences from Diplazontinae parasitoid wasps) and one
      deep (eight nuclear genes and a phylogenomic sequence for diverse microbial
      eukaryotes including Stramenopiles, Alveolata, and Rhizaria). The predicted power
      of resolution for the loci analyzed is consistent with the historic use of the
      genes in phylogenetics.

PMID- 22389444
TI  - The concept of exceptionality: a legal farce?
AB  - How do we decide which treatments should be offered by the National Health
      Service (NHS) when we cannot afford to fund them all? In the absence of a
      positive appraisal by the National Institute for Health and Clinical Excellence
      (NICE), which mandates the provision of a treatment by the NHS, Primary Care
      Trusts (PCTs) are free to decide whether to provide a particular drug to some, or
      all, of their population. However, as public bodies, it is a well-established
      principle of Administrative Law that PCTs are not at liberty to fetter the
      exercise of their own discretion. They must recognise the possibility that some
      patients will have exceptional circumstances, and as a consequence, any general
      policy prohibiting the funding of a drug cannot be absolute. In the absence of
      statutory guidance on what might constitute exceptional, clinicians are left
      guessing as to whether their patients might be eligible for funding on the
      grounds of exceptionality. Using the context of expensive cancer drugs, I will
      examine the concept of exceptionality from clinical, moral, and legal
      perspectives, focussing particularly on the role of social factors in determining
      exceptionality. I will review the cases where PCTs' decisions not to fund cancer
      drugs were subject to legal action and argue that the courts have provided little
      guidance on interpreting the term exceptional, and that the concept has a limited
      role to play in the allocation of scarce health resources at a local level.

PMID- 22389448
TI  - Evolutionary meta-analysis of association studies reveals ancient constraints
      affecting disease marker discovery.
AB  - Genome-wide disease association studies contrast genetic variation between
      disease cohorts and healthy populations to discover single nucleotide
      polymorphisms (SNPs) and other genetic markers revealing underlying genetic
      architectures of human diseases. Despite scores of efforts over the past decade,
      many reproducible genetic variants that explain substantial proportions of the
      heritable risk of common human diseases remain undiscovered. We have conducted a
      multispecies genomic analysis of 5,831 putative human risk variants for more than
      230 disease phenotypes reported in 2,021 studies. We find that the current
      approaches show a propensity for discovering disease-associated SNPs (dSNPs) at
      conserved genomic positions because the effect size (odds ratio) and allelic P
      value of genetic association of an SNP relates strongly to the evolutionary
      conservation of their genomic position. We propose a new measure for ranking SNPs
      that integrates evolutionary conservation scores and the P value (E-rank). Using
      published data from a large case-control study, we demonstrate that E-rank method
      prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic
      disease associations, many of which may explain greater proportions of genetic
      variance. Therefore, long-term evolutionary histories of genomic positions offer
      key practical utility in reassessing data from existing disease association
      studies, and in the design and analysis of future studies aimed at revealing the
      genetic basis of common human diseases.

PMID- 22389449
TI  - Expression of a truncated active form of VDAC1 in lung cancer associates with
      hypoxic cell survival and correlates with progression to chemotherapy resistance.
AB  - Resistance to chemotherapy-induced apoptosis of tumor cells represents a major
      hurdle to efficient cancer therapy. Although resistance is a characteristic of
      tumor cells that evolve in a low oxygen environment (hypoxia), the mechanisms
      involved remain elusive. We observed that mitochondria of certain hypoxic cells
      take on an enlarged appearance with reorganized cristae. In these cells, we found
      that a major mitochondrial protein regulating metabolism and apoptosis, the
      voltage-dependent anion channel 1 (VDAC1), was linked to chemoresistance when in
      a truncated (VDAC1-DeltaC) but active form. The formation of truncated VDAC1,
      which had a similar channel activity and voltage dependency as full-length, was
      hypoxia-inducible factor-1 (HIF-1)-dependent and could be inhibited in the
      presence of the tetracycline antibiotics doxycycline and minocycline, known
      inhibitors of metalloproteases. Its formation was also reversible upon cell
      reoxygenation and associated with cell survival through binding to the
      antiapoptotic protein hexokinase. Hypoxic cells containing VDAC1-DeltaC were less
      sensitive to staurosporine- and etoposide-induced cell death, and silencing of
      VDAC1-DeltaC or treatment with the tetracycline antibiotics restored sensitivity.
      Clinically, VDAC1-DeltaC was detected in tumor tissues of patients with lung
      adenocarcinomas and was found more frequently in large and late-stage tumors.
      Together, our findings show that via induction of VDAC1-DeltaC, HIF-1 confers
      selective protection from apoptosis that allows maintenance of ATP and cell
      survival in hypoxia. VDAC1-DeltaC may also hold promise as a biomarker for tumor
      progression in chemotherapy-resistant patients.

PMID- 22389450
TI  - A galectin-3-dependent pathway upregulates interleukin-6 in the microenvironment
      of human neuroblastoma.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine with a broad range of physiologic
      and pathologic functions. Because in cancer, IL-6 contributes to a
      microenvironment that promotes tumor cell survival, angiogenesis, and
      inflammation, understanding the mechanism responsible for its production is
      important. In neuroblastoma, the second most common solid tumor in children, IL-6
      is produced not by tumor cells but by stromal cells such as monocytes and bone
      marrow mesenchymal stem cells (BMMSC). Here we show that the production of IL-6
      in BMMSCs is in part stimulated by galectin-3 binding protein (Gal-3BP) secreted
      by neuroblastoma cells. We identified a distal region of the IL-6 promoter that
      contains 3 CCATT/enhancer binding protein (C/EBP) binding domains involved in the
      transcriptional upregulation of IL-6 by Gal-3BP. Gal-3BP interacted with Galectin
      3 (Gal-3) present in BMMSCs, and a Gal-3BP/Gal-3/Ras/MEK/ERK signaling pathway
      was responsible for the transcriptional upregulation of IL-6 in BMMSCs in which
      Gal-3 has a necessary function. In support of the role of this pathway in human
      neuroblastoma tumors, Gal-3BP was found to be present in tumor cells and in the
      adjacent extracellular matrix of 96% of 78 primary neuroblastoma tumor samples
      examined by immunohistochemistry. Considering the protumorigenic function of IL-6
      in cancer, this tumor cell-stromal cell interactive pathway could be a target for
      anticancer therapy.

PMID- 22389452
TI  - Type I and II IFNs inhibit Merkel cell carcinoma via modulation of the Merkel
      cell polyomavirus T antigens.
AB  - Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer
      associated with the Merkel cell polyomavirus (MCV). As MCC cell lines show
      oncogene addiction to the MCV T antigens, pharmacologic interference of the large
      T antigen (LTA) may represent an effective therapeutic approach for this deadly
      cancer. In this study, we investigated the effects of IFNs on MCC cell lines,
      especially on MCV-positive (MCV(+)) lines. Type I IFNs (i.e., Multiferon, a mix
      of different IFN-alpha subtypes, and IFN-beta) strongly inhibited the cellular
      viability. Cell-cycle analysis showed increased sub-G fractions for these cells
      upon IFN treatment indicating apoptotic cell death; these effects were less
      pronounced for IFN-gamma. Notably, this inhibitory effect of type I IFNs on
      MCV(+) MCC cell lines was associated with a reduced expression of the MCV LTA as
      well as an increased expression of promyelocytic leukemia (PML) protein, which is
      known to interfere with the function of the LTA. In addition, the intratumoral
      application of Multiferon resulted in a regression of MCV(+) but not MCV(-) MCCs
      in vivo. Together, our findings show that type I IFNs have a strong antitumor
      effect, which is at least in part explained by modulation of the virally encoded
      LTA.

PMID- 22389451
TI  - A RASSF1A polymorphism restricts p53/p73 activation and associates with poor
      survival and accelerated age of onset of soft tissue sarcoma.
AB  - RASSF1A (Ras association domain containing family 1A), a tumor suppressor gene
      that is frequently inactivated in human cancers, is phosphorylated by ataxia
      telangiectasia mutated (ATM) on Ser131 upon DNA damage, leading to activation of
      a p73-dependent apoptotic response. A single-nucleotide polymorphism located in
      the region of the key ATM activation site of RASSF1A predicts the conversion of
      alanine (encoded by the major G allele) to serine (encoded by the minor T allele)
      at residue 133 of RASSF1A (p.Ala133Ser). Secondary protein structure prediction
      studies suggest that an alpha helix containing the ATM recognition site is
      disrupted in the serine isoform of RASSF1A (RASSF1A-p.133Ser). In this study, we
      observed a reduced ability of ATM to recruit and phosphorylate RASSF1A-p.133Ser
      upon DNA damage. RASSF1A-p.133Ser failed to activate the MST2/LATS pathway, which
      is required for YAP/p73-mediated apoptosis, and negatively affected the
      activation of p53, culminating in a defective cellular response to DNA damage.
      Consistent with a defective p53 response, we found that male soft tissue sarcoma
      patients carrying the minor T allele encoding RASSF1A-p.133Ser exhibited poorer
      tumor-specific survival and earlier age of onset compared with patients
      homozygous for the major G allele. Our findings propose a model that suggests a
      certain subset of the population have inherently weaker p73/p53 activation due to
      inefficient signaling through RASSF1A, which affects both cancer incidence and
      survival.

PMID- 22389453
TI  - Intratracheal administration of a nanoparticle-based therapy with the angiotensin
      II type 2 receptor gene attenuates lung cancer growth.
AB  - Targeted gene delivery, transfection efficiency, and toxicity concerns remain a
      challenge for effective gene therapy. In this study, we dimerized the HIV-1 TAT
      peptide and formulated a nanoparticle vector (dTAT NP) to leverage the efficiency
      of this cell-penetrating strategy for tumor-targeted gene delivery in the setting
      of intratracheal administration. Expression efficiency for dTAT NP-encapsulated
      luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) was
      evaluated in Lewis lung carcinoma (LLC) cells cultured in vitro or in vivo in
      orthotopic tumor grafts in syngeneic mice. In cell culture, dTAT NP was an
      effective pDNA transfection vector with negligible cytotoxicity. Transfection
      efficiency was further increased by addition of calcium and glucose to dTAT/pDNA
      NP. In orthotopic tumor grafts, immunohistochemical analysis confirmed that dTAT
      NP successfully delivered pDNA to the tumor, where it was expressed primarily in
      tumor cells along with the bronchial epithelium. Notably, gene expression in
      tumor tissues persisted at least 14 days after intratracheal administration.
      Moreover, bolus administration of dTAT NP-encapsulated AT2R or TNF-related
      apoptosis-inducing ligand (TRAIL) pDNA markedly attenuated tumor growth. Taken
      together, our findings offer a preclinical proof-of-concept for a novel gene
      delivery system that offers an effective intratracheal strategy for administering
      lung cancer gene therapy.

PMID- 22389454
TI  - Evolution and architecture of the inner membrane complex in asexual and sexual
      stages of the malaria parasite.
AB  - The inner membrane complex (IMC) is a unifying morphological feature of all
      alveolate organisms. It consists of flattened vesicles underlying the plasma
      membrane and is interconnected with the cytoskeleton. Depending on the ecological
      niche of the organisms, the function of the IMC ranges from a fundamental role as
      reinforcement system to more specialized roles in motility and cytokinesis. In
      this article, we present a comprehensive evolutionary analysis of IMC components,
      which exemplifies the adaptive nature of the IMCs' protein composition. Focusing
      on eight structurally distinct proteins in the most prominent "genus" of the
      Alveolata-the malaria parasite Plasmodium-we demonstrate that the level of
      conservation is reflected in phenotypic characteristics, accentuated in
      differential spatial-temporal patterns of these proteins in the motile stages of
      the parasite's life cycle. Colocalization studies with the centromere and the
      spindle apparatus reveal their discriminative biogenesis. We also reveal that the
      IMC is an essential structural compartment for the development of the sexual
      stages of Plasmodium, as it seems to drive the morphological changes of the
      parasite during the long and multistaged process of sexual differentiation. We
      further found a Plasmodium-specific IMC membrane matrix protein that highlights
      transversal structures in gametocytes, which could represent a genus-specific
      structural innovation required by Plasmodium. We conclude that the IMC has an
      additional role during sexual development supporting morphogenesis of the cell,
      which in addition to its functions in the asexual stages highlights the
      multifunctional nature of the IMC in the Plasmodium life cycle.

PMID- 22389455
TI  - Detection of N526K-substituted penicillin-binding protein 3 conferring low-level
      mutational resistance to beta-lactam antibiotics in Haemophilus influenzae by
      disc diffusion testing on Mueller-Hinton agar according to EUCAST guidelines.
AB  - OBJECTIVES: EUCAST has recently authorized a new disc diffusion test for routine
      antimicrobial susceptibility testing of Haemophilus influenzae, calibrated to
      EUCAST MIC breakpoints. We investigated whether disc diffusion testing as
      recommended by EUCAST could discriminate strains of H. influenzae carrying the
      N526K substitution in penicillin-binding protein 3 from the wild-type population.
      METHODS: A total of 170 recent clinical isolates, genetically characterized for
      the presence of acquired and mutational resistance mechanisms, were tested by
      disc diffusion of beta-lactam antibiotics on supplemented Mueller-Hinton agar.
      Tentative epidemiological breakpoint values for the presence of the N526K
      substitution were suggested for various beta-lactams, and the performances were
      calculated. RESULTS: Epidemiological cut-off values of 19/20 mm for ampicillin (2
      MUg) and 11/12 mm for benzylpenicillin (1 U) accurately categorized 96% of the
      study strains, and outperformed cephalosporin-containing discs in the
      discrimination of mutational resistance in beta-lactamase-non-producing isolates.
      Current EUCAST interpretative criteria for the categorization of clinical
      resistance showed concordance between resistance rates based on MIC and zone
      diameter breakpoints for both ampicillin and cefuroxime, but categorization of
      individual isolates was not consistent. CONCLUSIONS: Disc diffusion testing of H.
      influenzae accurately identified beta-lactamase-non-producing isolates with the
      N526K substitution by use of discs containing low amounts of penicillins.
      Cephalosporin-containing discs could detect mutational resistance in beta
      lactamase-producing isolates, but performed with reduced specificity.

PMID- 22389456
TI  - Diabetic murine models for Acinetobacter baumannii infection.
AB  - OBJECTIVES: Extremely drug-resistant (XDR; i.e. resistant to all antibiotics
      except colistin or tigecycline) Acinetobacter baumannii has emerged as one of the
      most common and highly antibiotic-resistant causes of infection. Diabetes is a
      risk factor for acquisition of and worse outcomes from A. baumannii infection. We
      sought to develop diabetic mouse models of A. baumannii bacteraemia and pneumonia
      and validate these models by comparing the efficacy of antibiotic treatment in
      these models with the established neutropenic mouse models. METHODS: Diabetic or
      neutropenic mice were infected via intravenous inoculation or inhalation in an
      aerosol chamber with an XDR A. baumannii. Treatment with colistin started 24 h
      after infection and continued daily for 7 days. Survival served as the primary
      endpoint while tissue bacterial burden and histopathological examination served
      as secondary endpoints. RESULTS: Lethal infection was achieved for the
      neutropenic and diabetic mice when infected intravenously or via inhalation.
      Neutropenic mice were more susceptible to infection than diabetic mice in the
      pneumonia model and equally susceptible in the bacteraemia model. Both models of
      bacteraemia were sensitive enough to detect virulence differences among different
      clinical strains of A. baumannii. In the pneumonia model, colistin treatment was
      effective in improving survival, reducing lung bacterial burden and
      histologically resolving the infection compared with placebo only in diabetic
      mice. CONCLUSIONS: We developed novel models of A. baumannii bacteraemia and
      pneumonia in diabetic mice. These models can be used to study mechanisms of
      infection, develop immunotherapeutic strategies and evaluate drug efficacies
      against highly lethal A. baumannii infections.

PMID- 22389457
TI  - Hospital readmission in persons with stroke following postacute inpatient
      rehabilitation.
AB  - BACKGROUND: Readmission is an important quality indicator following acute care
      hospitalization. We examined factors associated with hospital readmission in
      persons with stroke following postacute inpatient rehabilitation. METHODS:
      Prospective cohort study including 674 persons with stroke who received
      rehabilitation at 11 facilities located in eight states and the District of
      Columbia. Measures included hospital readmission within 3 months of discharge,
      sociodemographic characteristics, length of stay, primary payment source,
      comorbidities, stroke type, standardized assessments of motor and cognitive
      function, depressive symptoms, and social support. RESULTS: Mean age was 71.5
      years (SD = 10.5). Twenty-five percent of patients reported high depressive
      symptoms. Overall, 18% (n = 122) of the sample was rehospitalized. Univariate
      analyses showed that people who were rehospitalized were more likely (p < .05) to
      be non-Hispanic white, married, demonstrate less functional independence at
      discharge, experience longer lengths of stay in rehabilitation, and report more
      depressive symptoms and lower social support. In the fully adjusted multivariable
      hierarchical generalized linear model, motor functional status (OR = 0.98, 95% CI
      0.96-0.99), depressive symptoms (OR = 1.80, 95% CI 1.06-3.05), and social support
      (OR = 2.28, 95% CI 1.29-4.03) remained statistically significant. In addition, a
      minority-by-depressive symptoms interaction term also reached statistical
      significance. CONCLUSION: Functional status, depressive symptoms, and social
      support were important predictors of hospital readmission. These variables are
      not included in most administrative data sets. Future research to develop useful
      risk-adjustment models for rehospitalization following postacute inpatient
      rehabilitation services should include large diverse samples and explore
      practical sources for additional meaningful information.

PMID- 22389458
TI  - A prospective study of gait performance and subsequent cognitive decline in a
      general population of older Japanese.
AB  - BACKGROUND: Gait speed is a good predictor of cognitive decline in later life.
      However, it is not known whether step length or step frequency is better for
      predicting such decline. This study aimed to compare the predictive value for
      cognitive decline of gait performance measures in a population of older Japanese.
      METHODS: Among 853 cognitively intact adults aged 70 years or older who
      participated in a baseline survey, 666 (mean age, 75.5 [SD 4.4] years; women,
      59.3%) were reevaluated at least once during the subsequent 4-year period.
      Cognition was assessed by Mini-Mental State Examination (MMSE), and cognitive
      decline was defined as a decrease of three points or more on the Mini-Mental
      State Examination during follow-up. RESULTS: During a median follow-up of 2.7
      years, 110 adults (16.5%) had cognitive decline. Among the measures of gait
      performance (speed, step length, and frequency), step length was the most
      predictive of cognitive decline. After controlling for important confounders,
      older men in the lowest and middle tertiles of step length at maximum speed and
      older women in the lowest and middle tertiles of step length at usual speed were
      4.42 (95% confidence interval: 1.65-11.8), 2.17 (0.82-5.71), 5.76 (2.15-15.4),
      and 2.44 (0.94-6.35) times as likely to develop cognitive decline, respectively,
      as those of the same sex and walking speed who were in the highest tertile.
      CONCLUSIONS: Step length was an independent predictor of cognitive decline in a
      general population of older adults and may be a better predictor than overall
      gait speed of such decline.

PMID- 22389459
TI  - Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity
      and arterial stiffness in very old Zucker rats.
AB  - To analyze age-related interactions between obesity, its associated metabolic
      disorders, and macrocirculation, we studied large artery stiffness and fatty acid
      responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very
      old). Systolic arterial pressure was higher in old obese than in old lean rats
      (178 +/- 10 vs 134 +/- 8 mmHg, respectively). Carotid elastic modulus-wall stress
      curves showed increased age-dependent arterial stiffening, which was greater in
      obese animals. Old obese exhibited endothelial dysfunction with increased
      systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels
      (1,866 +/- 177 vs 310 +/- 34 MUg/MUL in lean animals). In old obese, linoleate
      and palmitate increased contractility to phenylephrine and reduced relaxation to
      acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial
      aging observed at 80 weeks. The early increase in free fatty acids may be a key
      effector in the severe arterial stiffness of the aged obese Zucker model.

PMID- 22389460
TI  - Effects of estrogen replacement and lower androgen status on skeletal muscle
      collagen and myofibrillar protein synthesis in postmenopausal women.
AB  - Our aim was to determine synthesis rate of myofibrillar and collagen proteins in
      20 postmenopausal women, who were either nonusers (Controls) or users of estrogen
      replacement therapy (ERT) after hysterectomy/oophorectomy. Myofibrillar and
      muscle collagen protein fractional synthesis rate (FSR) were determined in a
      nonexercised leg and 24 hours after exercise in the contralateral leg. A
      significant interaction between treatment and mechanical loading was observed in
      myofibrillar protein FSR. At rest, myofibrillar protein FSR was found to be lower
      in ERT users than in Controls. Exercise enhanced myofibrillar protein FSR only in
      ERT users. Similarly, muscle collagen FSR tended to be lower in ERT users
      compared with Controls. In ERT participants, the androgen profile was reduced,
      whereas estradiol and sex hormone-binding globulin were higher. In conclusion, at
      rest, myofibrillar protein FSR was lower in hysterectomized/oophorectomized women
      using ERT compared with healthy postmenopausal women. Nevertheless, resistance
      exercise in combination with ERT seems to have a counteracting effect on
      myofibrillar FSR in hysterectomized/oophorectomized women.

PMID- 22389461
TI  - Prevalence of potentially preventable unplanned hospitalizations caused by
      therapeutic failures and adverse drug withdrawal events among older veterans.
AB  - Background. Studies of drug-related hospitalizations have focused on adverse drug
      reactions, but few data are available on therapeutic failures (TFs) and adverse
      drug withdrawal events (ADWEs) leading to hospitalization among community
      dwelling older adults. Thus, we sought to describe the prevalence of unplanned
      hospitalizations caused by TFs and ADWEs. In addition, we evaluated factors
      associated with these events in a nationally representative sample of older
      Veterans.  Methods. This study included 678 randomly selected unplanned
      hospitalizations of older (age >= 65 years) Veterans between December 1, 2003,
      and November 9, 2006. The main outcomes were hospitalizations caused by a TF
      and/or an ADWE as determined by a pair of health professionals from review of
      medication charts and application of the Therapeutic Failure Questionnaire and/or
      Naranjo ADWE algorithm, respectively. Preventability (ie, medication error) of
      the admission was also assessed.  Results. Thirty-four TFs and eight ADWEs
      involving 54 drugs were associated with 40 (5.9%) Veterans' hospitalizations; of
      these admissions, 90.0% (36/40) were rated as potentially preventable mostly due
      to medication nonadherence and suboptimal prescribing. The most common TFs that
      occurred were heart failure exacerbations (n = 8), coronary heart disease
      symptoms (n = 6), tachyarrhythmias (n = 3), and chronic obstructive pulmonary
      disease exacerbations (n = 3). Half (4/8) of the ADWEs that occurred were
      cardiovascular in nature. Multivariable logistic regression modeling indicated
      that black Veterans (adjusted odds ratio 2.92, 95% CI 1.25-6.80) were
      significantly more likely to experience a TF-related admission compared with
      white Veterans.  Conclusions. TF-related unplanned hospitalizations occur more
      frequently than ADWE-related admissions among older Veterans. Almost all TFs
      and/or ADWEs are potentially preventable.

PMID- 22389462
TI  - Oxidative damage, platelet activation, and inflammation to predict mobility
      disability and mortality in older persons: results from the health aging and body
      composition study.
AB  - BACKGROUND: Inflammation, oxidative damage, and platelet activation are
      hypothesized biological mechanisms driving the disablement process. The aim of
      the present study is to assess whether biomarkers representing these mechanisms
      predicted major adverse health-related events in older persons. METHODS: Data are
      from 2,234 community-dwelling nondisabled older persons enrolled in the Health
      Aging and Body Composition study. Biomarkers of lipid peroxidation (ie, urinary
      levels of 8-iso-prostaglandin F(2alpha)), platelet activation (ie, urinary levels
      of 11-dehydro-thromboxane B(2)), and inflammation (serum concentrations of
      interleukin-6) were considered as independent variables of interest and tested in
      Cox proportional hazard models as predictors of (severe) mobility disability and
      overall mortality. RESULTS: The sample's (women 48.0%, whites 64.3%) mean age was
      74.6 (SD 2.9) years. During the follow-up (median 11.4 years), 792 (35.5%), 269
      (12.0%), and 942 (42.2%) events of mobility disability, severe mobility
      disability, and mortality occurred, respectively. Only interleukin-6 showed
      significant independent associations with the onset of all the study outcomes.
      Higher levels of urinary 8-iso-prostaglandin F(2alpha) and 11-dehydro-thromboxane
      B(2) independently predicted increased risk of death (hazard ratio 1.10, 95%
      confidence interval 1.03-1.19 and hazard ratio 1.14, 95% confidence interval 1.06
      1.23, respectively). No significant interactions of gender, race, cardiovascular
      disease, diabetes, and antiplatelet drugs were detected on the studied
      relationships. CONCLUSIONS: The inflammatory marker interleukin-6 is confirmed to
      be a robust predictor for the onset of negative health-related events.
      Participants with higher urinary levels of 8-iso-prostaglandin F(2alpha) and 11
      dehydro-thromboxane B(2) presented a higher mortality risk.

PMID- 22389463
TI  - The association of blood pressure and mortality differs by self-reported walking
      speed in older Latinos.
AB  - BACKGROUND: In some older adults, higher blood pressure (BP) is associated with a
      lower risk of mortality. We hypothesized that higher BP would be associated with
      greater mortality in high-functioning elders and lower mortality in elders with
      lower functional status. METHODS: Participants were 1,562 Latino adults aged 60
      101 years in the Sacramento Area Latino Study on Aging. Functional status was
      measured by self-reported walking speed, and BP was measured by automatic
      sphygmomanometer. Death information was determined from vital statistics records.
      RESULTS: There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean
      BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140
      mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08,
      respectively. The relationship between systolic BP and mortality varied by self
      reported walking speed: The adjusted hazard ratio for mortality in slow walkers
      was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and
      1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for
      interaction <.001). We found a similar pattern for diastolic BP, although the
      interaction did not reach statistical significance; the adjusted hazard ratio per
      10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in
      slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p
      value for interaction = .06). CONCLUSIONS: In high-functioning older adults,
      elevated systolic BP is a risk factor for all-cause mortality. If confirmed in
      other studies, the assessment of functional status may help to identify persons
      who are most at-risk for adverse outcomes related to high BP.

PMID- 22389464
TI  - Chronic exercise modifies age-related telomere dynamics in a tissue-specific
      fashion.
AB  - We evaluated the impact of long-term exercise on telomere dynamics in wild
      derived short telomere mice (CAST/Ei) over 1 year. We observed significant
      telomere shortening in liver and cardiac tissues in sedentary 1-year-old mice
      compared with young (8 weeks) baseline mice that were attenuated in exercised 1
      year-old animals. In contrast, skeletal muscle exhibited significant telomere
      shortening in exercise mice compared with sedentary and young mice. Telomerase
      enzyme activity was increased in skeletal muscle of exercise compared with
      sedentary animals but was similar in cardiac and liver tissues. We observed
      significant age-related decreases in expression of telomere-related genes that
      were attenuated by exercise in cardiac and skeletal muscle but not liver. Protein
      content of TRF1 was significantly increased in plantaris muscle with age. In
      summary, long-term exercise altered telomere dynamics, slowing age-related
      decreases in telomere length in cardiac and liver tissue but contributing to
      shortening in exercised skeletal muscle.

PMID- 22389465
TI  - The association of dementia with upper arm and waist circumference in seven low-
      and middle-income countries: the 10/66 cross-sectional surveys.
AB  - BACKGROUND: Weight loss in dementia contributes to morbidity and mortality but
      the distribution of anthropometric change and its consistency between populations
      are less clear. Our aim was to investigate and compare the associations of
      dementia with waist and upper arm circumference in elders from seven low- and
      middle-income nations. METHODS: Cross-sectional surveys were conducted of 15,022
      residents aged 65 years and older in Cuba, Mexico, Venezuela, Peru, Dominican
      Republic, China, and India. Dementia was assessed using a cross-culturally
      validated algorithm, and anthropometric measurements were taken. Associations
      with dementia and dementia severity (clinical dementia rating scale) were
      investigated in linear regression models, with fixed-effects meta-analyses used
      to investigate between-country heterogeneity. RESULTS: Dementia and increased
      dementia severity were both associated with smaller arm and waist circumferences
      with little evidence of confounding by sociodemographic and health status.
      Associations between dementia/clinical dementia rating and arm circumference were
      homogeneous between countries (Higgins I(2) 0% and 7%, respectively), whereas
      those with waist circumference were more heterogeneous (Higgins I(2) 67% and 62%,
      respectively). CONCLUSIONS: Although cross-sectional, our findings are consistent
      with prospective observations of weight loss in dementia and suggest loss of both
      muscle and fat-the former being consistent across different settings and the
      latter being more context dependent.

PMID- 22389466
TI  - Understanding dementia prevalence among centenarians.
AB  - The goals of this article are to (a) establish the concurrent and clinical
      validity of the Global Deterioration scale in assessing cognitive functions and
      stages of dementia among centenarians, (b) identify the prevalence of all-cause
      dementia in representative samples of centenarians, and (c) demonstrate how
      variations in sample demographic characteristics could significantly affect
      estimates of dementia prevalence. A quarter of the 244 centenarians in a
      population-based sample had no objective evidence of memory deficits. Another
      quarter showed signs of transient confusion, and about half showed classical
      behavioral signs of dementia with about 15% in each of Global Deterioration scale
      stages 4-6 and about 5% in the most severe stage 7. Variations in age, gender,
      race, residence status, and education of the study sample as well as criteria
      used for dementia rating were found to affect prevalence.

PMID- 22389467
TI  - Effects of balance training on muscle coactivation during postural control in
      older adults: a randomized controlled trial.
AB  - BACKGROUND: Recently, several studies have reported age-associated increases in
      muscle coactivation during postural control. A rigid posture induced by strong
      muscle coactivation reduces the degree of freedom to be organized by the postural
      control system. The purpose of this study was to clarify the effect of balance
      training on muscle coactivation during postural control in older adults. METHODS:
      Forty-eight subjects were randomized into an intervention (mean age: 81.0 +/- 6.9
      years) and a control group (mean age: 81.6 +/- 6.4 years). The control group did
      not receive any intervention. Postural control ability (postural sway during
      quiet standing, functional reach, and functional stability boundary) was assessed
      before and after the intervention. A cocontraction index was measured during the
      postural control tasks to assess muscle coactivation. RESULTS: Cocontraction
      index values in the intervention group significantly decreased following the
      intervention phase for functional reach (p < .0125). Cocontraction index values
      had a tendency to decrease during functional stability boundary for forward and
      quiet standing tasks. Functional improvements were observed in some of the tasks
      after the intervention, that is, functional reach, functional stability boundary
      for forward, one-leg stance, and timed up and go (p < .05). CONCLUSIONS: Our
      study raised the possibility that balance training for older adults was
      associated with decreases in muscle coactivation during postural control.
      Postural control exercise could potentially lead older adults to develop more
      efficient postural control strategies without increasing muscle coactivation.
      Further research is needed to clarify in greater detail the effects of changes in
      muscle coactivation.

PMID- 22389468
TI  - Sensitivity of selected human tumor models to PF-04217903, a novel selective c
      Met kinase inhibitor.
AB  - The c-Met pathway has been implicated in a variety of human cancers for its
      critical role in tumor growth, invasion, and metastasis. PF-04217903 is a novel
      ATP-competitive small-molecule inhibitor of c-Met kinase. PF-04217903 showed more
      than 1,000-fold selectivity for c-Met compared with more than 150 kinases, making
      it one of the most selective c-Met inhibitors described to date. PF-04217903
      inhibited tumor cell proliferation, survival, migration/invasion in MET-amplified
      cell lines in vitro, and showed marked antitumor activity in tumor models
      harboring either MET gene amplification or a hepatocyte growth factor (HGF)/c-Met
      autocrine loop at well-tolerated dose levels in vivo. Antitumor efficacy of PF
      04217903 was dose-dependent and showed a strong correlation with inhibition of c
      Met phosphorylation, downstream signaling, and tumor cell proliferation/survival.
      In human xenograft models that express relatively high levels of c-Met, complete
      inhibition of c-Met activity by PF-04217903 only led to partial tumor growth
      inhibition (38%-46%) in vivo. The combination of PF-04217903 with Recepteur
      d'origine nantais (RON) short hairpin RNA (shRNA) knockdown in the HT29 model
      that also expresses activated RON kinase-induced tumor cell apoptosis and
      resulted in enhanced antitumor efficacy (77%) compared with either PF-04217903
      (38%) or RON shRNA alone (56%). PF-04217903 also showed potent antiangiogenic
      properties in vitro and in vivo. Furthermore, PF-04217903 strongly induced
      phospho-PDGFRbeta (platelet-derived growth factor receptor) levels in U87MG
      xenograft tumors, indicating a possible oncogene switching mechanism in tumor
      cell signaling as a potential resistance mechanism that might compromise tumor
      responses to c-Met inhibitors. Collectively, these results show the use of highly
      selective inhibition of c-Met and provide insight toward targeting tumors
      exhibiting different mechanisms of c-Met dysregulation.

PMID- 22389469
TI  - Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces
      cell growth inhibition and apoptosis.
AB  - The transcription factor c-Myc is important in cell fate decisions and is
      frequently overexpressed in cancer cells, making it an attractive therapeutic
      target. Natural compounds are among the current strategies aimed at targeting c
      Myc, but their modes of action still need to be characterized. To explore the
      mechanisms underlying the anticancer activity of a natural diterpenoid, oridonin,
      we conducted miRNA expression profiling and statistical analyses that strongly
      suggested that c-Myc was a potential molecular target of oridonin. Furthermore,
      experimental data showed that oridonin significantly reduced c-Myc protein levels
      in vitro and in vivo and that this reduction was mediated by the ubiquitin
      proteasome system. Fbw7, a component of the ubiquitin-proteasome system and an E3
      ubiquitin ligase of c-Myc, was upregulated rapidly in K562 cells and other
      leukemia and lymphoma cells, resulting in the rapid turnover of c-Myc. In cell
      lines harboring mutations in the WD domain of Fbw7, the degradation of c-Myc
      induced by oridonin was attenuated during short-term treatment. GSK-3, an Fbw7
      priming kinase, was also activated by oridonin, along with an increase in T58
      phosphorylated c-Myc. Furthermore, the knockdown of Fbw7 or the forced expression
      of stable c-Myc resulted in reduced sensitization to oridonin-induced apoptosis.
      Our observations help to clarify the anticancer mechanisms of oridonin and shed
      light on the application of this natural compound as an Fbw7-c-Myc pathway
      targeting agent in cancer treatment.

PMID- 22389470
TI  - HER2 as therapeutic target for overcoming ATP-binding cassette transporter
      mediated chemoresistance in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) easily acquires multidrug resistance after
      successful initial therapy. Overexpression of ATP-binding cassette (ABC)
      transporters is important for the multidrug resistance. Among them, ABCB1 and
      ABCG2 are known to be upregulated in chemoresistant SCLC cells. We found that
      human epidermal growth factor receptor 2 (HER2) expressions are also upregulated
      in chemoresistant SBC-3/ETP, SBC-3/SN-38, and SBC-3/CDDP cells, compared with
      chemosensitive SBC-3 cells. Lapatinib, a tyrosine kinase inhibitor of HER2, could
      not suppress proliferation of these HER2-positive SCLC cells alone but
      successfully restored chemosensitivity to etoposide and SN-38 with a clinically
      applicable concentration. The reversal effect of lapatinib was thought to be
      caused by inhibition of drug efflux pump functions of ABC transporters, although
      lapatinib itself has been reported to be a substrate for them. Moreover, knocking
      down of HER2 by an short interfering RNA weakened the effect of lapatinib on
      ABCB1, indicating the involvement of HER2 in the inhibitory mechanisms. Notably,
      we showed that caveolin-1 and Src play key roles in modulating ABCB1 function via
      HER2 inactivation. In SBC-3/ETP cells, dephosphorylation of HER2 by lapatinib
      activates Src and successively leads to increased caveolin-1 phosphorylation.
      Through this process, caveolin-1 dissociates from HER2 and strengthens
      association with ABCB1, and finally impairs the pump functions. Furthermore, we
      showed that treatment by lapatinib in combination with etoposide or irinotecan
      significantly suppresses the growth of subcutaneous SBC-3/ETP and SBC-3/SN-38
      tumors in mice, respectively. Collectively, these results indicate that
      combination therapy with lapatinib and cytotoxic agents could conquer ABC
      transporter-mediated chemoresistance especially in HER2-positive SCLC.

PMID- 22389471
TI  - Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance
      to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations.
AB  - Recent results from clinical trials with the BRAF inhibitors GSK2118436
      (dabrafenib) and PLX4032 (vemurafenib) have shown encouraging response rates;
      however, the duration of response has been limited. To identify determinants of
      acquired resistance to GSK2118436 and strategies to overcome the resistance, we
      isolated GSK2118436 drug-resistant clones from the A375 BRAF(V600E) and the
      YUSIT1 BRAF(V600K) melanoma cell lines. These clones also showed reduced
      sensitivity to the allosteric mitogen-activated protein/extracellular signal
      regulated kinase (MEK) inhibitor GSK1120212 (trametinib). Genetic
      characterization of these clones identified an in-frame deletion in MEK1
      (MEK1(K59del)) or NRAS mutation (NRAS(Q61K) and/or NRAS(A146T)) with and without
      MEK1(P387S) in the BRAF(V600E) background and NRAS(Q61K) in the BRAF(V600K)
      background. Stable knockdown of NRAS with short hairpin RNA partially restored
      GSK2118436 sensitivity in mutant NRAS clones, whereas expression of NRAS(Q61K) or
      NRAS(A146T) in the A375 parental cells decreased sensitivity to GSK2118436.
      Similarly, expression of MEK1(K59del), but not MEK1(P387S), decreased sensitivity
      of A375 cells to GSK2118436. The combination of GSK2118436 and GSK1120212
      effectively inhibited cell growth, decreased ERK phosphorylation, decreased
      cyclin D1 protein, and increased p27(kip1) protein in the resistant clones.
      Moreover, the combination of GSK2118436 or GSK1120212 with the phosphoinositide 3
      kinase/mTOR inhibitor GSK2126458 enhanced cell growth inhibition and decreased S6
      ribosomal protein phosphorylation in these clones. Our results show that NRAS
      and/or MEK mutations contribute to BRAF inhibitor resistance in vitro, and the
      combination of GSK2118436 and GSK1120212 overcomes this resistance. In addition,
      these resistant clones respond to the combination of GSK2126458 with GSK2118436
      or GSK1120212. Clinical trials are ongoing or planned to test these combinations.

PMID- 22389472
TI  - Inhibition of OCTN2-mediated transport of carnitine by etoposide.
AB  - OCTN2 is a bifunctional transporter that reabsorbs filtered carnitine in a sodium
      dependent manner and secretes organic cations into urine as a proton antiport
      mechanism. We hypothesized that inhibition of OCTN2 by anticancer drugs can
      influence carnitine resorption. OCTN2-mediated transport inhibition by anticancer
      drugs was assessed using cells transfected with human OCTN2 (hOCTN2) or mouse
      Octn2 (mOctn2). Excretion of carnitine and acetylcarnitine was measured in urine
      collected from mice and pediatric patients with cancer before and after
      administration of etoposide. Five of 27 tested drugs (50-100 MUmol/L) inhibited
      hOCTN2-mediated carnitine uptake by 42% to 85% (P < 0.001). Of these inhibitors,
      etoposide was itself a transported substrate of hOCTN2 and mOctn2. Etoposide
      uptake by hOCTN2 was reversed in the presence of excess carnitine. This
      competitive inhibitory mechanism was confirmed in an in silico molecular docking
      analysis. In addition, etoposide inhibited the transcellular apical-to
      basolateral flux of carnitine in kidney cells. Etoposide was also associated with
      a significant urinary loss of carnitine in mice (~1.5-fold) and in patients with
      cancer (~2.4-fold). Collectively, these findings indicate that etoposide can
      inhibit hOCTN2 function, potentially disturb carnitine homeostasis, and that this
      phenomenon can contribute to treatment-related toxicities.

PMID- 22389473
TI  - Estrogen regulates endothelial migration via plasminogen activator inhibitor (PAI
      1).
AB  - Endothelial plasminogen activator inhibitor (PAI-1) controls vascular remodeling,
      angiogenesis and fibrinolysis. PAI-1 blood levels in women are related to
      estrogen. The aim of this study was to characterize the signaling pathways
      through which estrogen regulates PAI-1 in endothelial cells. Furthermore, we
      aimed to investigate whether PAI-1 is implicated in the control of endothelial
      migration by estrogen. Cultured human umbilical vein endothelial cells (HUVECs)
      and ovariectomized rats were used to test the effects of 17beta-estradiol (E(2))
      on PAI-1 expression and its role on endothelial migration. At physiological
      concentrations, E(2) increases the expression of PAI-1 in HUVEC within 6-12 h
      through activation of a signaling cascade initiated by estrogen receptor alpha
      and involving G proteins, phosphatidylinositol-3-OH kinase and Rho-associated
      kinase II. ROCK-II activation turns into an over-expression of c-Jun and c-Fos
      that is required for E(2)-induced expression of PAI-1. Estrogen-induced PAI-1
      expression is implicated in HUVEC horizontal migration. PAI-1 regulation is found
      also in vivo, in female rats, where ovariectomy is associated with reduced PAI-1
      expression, while estrogen replacement counteracts this change. In conclusion,
      E(2) increases PAI-1 synthesis in human endothelial cells and in rodent aorta
      through a G protein-initiated signaling that targets early-immediate gene
      expression. This regulatory pathway is implicated in endothelial cell migration.
      These findings describe new mechanisms of action of estrogens in the vessels,
      which may be important for vascular remodeling and hemostasis.

PMID- 22389474
TI  - Glutamine synthetase and glucose-6-phosphate isomerase are adhesive moonlighting
      proteins of Lactobacillus crispatus released by epithelial cathelicidin LL-37.
AB  - Glutamine synthetase (GS) and glucose-6-phosphate isomerase (GPI) were identified
      as novel adhesive moonlighting proteins of Lactobacillus crispatus ST1. Both
      proteins were bound onto the bacterial surface at acidic pHs, whereas a
      suspension of the cells to pH 8 caused their release into the buffer, a pattern
      previously observed with surface-bound enolase and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) of L. crispatus. The pH shift was associated with a rapid
      and transient increase in cell wall permeability, as measured by cell staining
      with propidium iodide. A gradual increase in the release of the four moonlighting
      proteins was also observed after the treatment of L. crispatus ST1 cells with
      increasing concentrations of the antimicrobial cationic peptide LL-37, which
      kills bacteria by disturbing membrane integrity and was here observed to increase
      the cell wall permeability of L. crispatus ST1. At pH 4, the fusion proteins
      His(6)-GS, His(6)-GPI, His(6)-enolase, and His(6)-GAPDH showed localized binding
      to cell division septa and poles of L. crispatus ST1 cells, whereas no binding to
      Lactobacillus rhamnosus GG was detected. Strain ST1 showed a pH-dependent
      adherence to the basement membrane preparation Matrigel. Purified His(6)-GS and
      His(6)-GPI proteins bound to type I collagen, and His(6)-GS also bound to
      laminin, and their level of binding was higher at pH 5.5 than at pH 6.5. His(6)
      GS also expressed a plasminogen receptor function. The results show the strain
      dependent surface association of moonlighting proteins in lactobacilli and that
      these proteins are released from the L. crispatus surface after cell trauma,
      under conditions of alkaline stress, or in the presence of the antimicrobial
      peptide LL-37 produced by human cells.

PMID- 22389475
TI  - Postgenomic analyses reveal development of infectious Anaplasma phagocytophilum
      during transmission from ticks to mice.
AB  - Obligate intracellular bacteria of the Rickettsiales order have evolved to
      colonize both arthropod and mammalian hosts, but few details are known about the
      bacterial adaptations that occur during transmission from blood-feeding
      arthropods to mammals. Here we apply proteomics and transcriptome sequencing to
      Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in
      Ixodes scapularis tick salivary glands, to detect proteins or genes expressed by
      the pathogen during transmission feeding by the tick. We detected expression of
      139 genes, representing 11% of the open reading frames (ORFs) in the A.
      phagocytophilum genome. The predominant categories of proteins were ribosomal
      proteins, cell surface proteins, chaperones, and uncharacterized proteins. There
      was no evidence of DNA replication enzymes, suggesting that most of the A.
      phagocytophilum cells were no longer dividing. Instead, protein expression
      reflected conversion to the extracellular, infectious "dense-core" (DC) form.
      High expression of a DC-specific marker, APH_1235, further suggested this
      developmental transition in ticks. We showed that blocking APH_1235 with
      antibodies reduced A. phagocytophilum infection levels in mammalian cell culture.
      This work represents a starting point for clarifying essential proteins expressed
      by A. phagocytophilum during transmission from ticks to mammals and demonstrates
      that the abundantly expressed, DC-associated APH_1235 protein is important during
      in vivo infection by A. phagocytophilum.

PMID- 22389476
TI  - Working together for the common good: cell-cell communication in bacteria.
AB  - The 4th ASM Conference on Cell-Cell Communication in Bacteria was held in Miami,
      FL, from 6 to 9 November 2011. This review highlights three key themes that
      emerged from the many exciting talks and poster presentations in the area of
      quorum sensing: sociomicrobiology, signal transduction mechanisms, and
      interspecies communication.

PMID- 22389477
TI  - Zinc starvation response in a cyanobacterium revealed.

PMID- 22389479
TI  - Robust translation of the nucleoid protein Fis requires a remote upstream AU
      element and is enhanced by RNA secondary structure.
AB  - Synthesis of the Fis nucleoid protein rapidly increases in response to nutrient
      upshifts, and Fis is one of the most abundant DNA binding proteins in Escherichia
      coli under nutrient-rich growth conditions. Previous work has shown that control
      of Fis synthesis occurs at transcription initiation of the dusB-fis operon. We
      show here that while translation of the dihydrouridine synthase gene dusB is low,
      unusual mechanisms operate to enable robust translation of fis. At least two RNA
      sequence elements located within the dusB coding region are responsible for high
      fis translation. The most important is an AU element centered 35 nucleotides (nt)
      upstream of the fis AUG, which may function as a binding site for ribosomal
      protein S1. In addition, a 44-nt segment located upstream of the AU element and
      predicted to form a stem-loop secondary structure plays a prominent role in
      enhancing fis translation. On the other hand, mutations close to the AUG,
      including over a potential Shine-Dalgarno sequence, have little effect on Fis
      protein levels. The AU element and stem-loop regions are phylogenetically
      conserved within dusB-fis operons of representative enteric bacteria.

PMID- 22389478
TI  - Sticky situations: key components that control bacterial surface attachment.
AB  - The formation of bacterial biofilms is initiated by cells transitioning from the
      free-swimming mode of growth to a surface. This review is aimed at highlighting
      the common themes that have emerged in recent research regarding the key
      components, signals, and cues that aid in the transition and those involved in
      establishing a more permanent surface association during initial attachment.

PMID- 22389480
TI  - A global investigation of the Bacillus subtilis iron-sparing response identifies
      major changes in metabolism.
AB  - The Bacillus subtilis ferric uptake regulator (Fur) protein is the major sensor
      of cellular iron status. When iron is limiting for growth, derepression of the
      Fur regulon increases the cellular capacity for iron uptake and mobilizes an iron
      sparing response mediated in large part by a small noncoding RNA named FsrA. FsrA
      functions, in collaboration with three small basic proteins (FbpABC), to repress
      many "low-priority" iron-containing enzymes. We have used transcriptome analyses
      to gain insights into the scope of the iron-sparing response and to define
      subsets of genes dependent for their repression on FsrA, FbpAB, and/or FbpC.
      Enzymes of the tricarboxylic acid (TCA) cycle, including aconitase and succinate
      dehydrogenase (SDH), are major targets of FsrA-mediated repression, and as a
      consequence, flux through this pathway is significantly decreased in a fur
      mutant. FsrA also represses the DctP dicarboxylate permease and the iron-sulfur
      containing enzyme glutamate synthase (GltAB), which serves as a central link
      between carbon and nitrogen metabolism. Allele-specific suppression analysis was
      used to document a direct RNA-RNA interaction between the FsrA small RNA (sRNA)
      and the gltAB leader region. We further demonstrated that distinct regions of
      FsrA are required for the translational repression of the GltAB and SDH enzyme
      complexes.

PMID- 22389481
TI  - Long-range transcriptional control of an operon necessary for virulence-critical
      ESX-1 secretion in Mycobacterium tuberculosis.
AB  - The ESX-1 secretion system of Mycobacterium tuberculosis has to be precisely
      regulated since the secreted proteins, although required for a successful
      virulent infection, are highly antigenic and their continued secretion would
      alert the immune system to the infection. The transcription of a five-gene operon
      containing espACD-Rv3613c-Rv3612c, which is required for ESX-1 secretion and is
      essential for virulence, was shown to be positively regulated by the EspR
      transcription factor. Thus, transcription from the start site, found to be
      located 67 bp upstream of espA, was dependent upon EspR enhancer-like sequences
      far upstream (between 884 and 1,004 bp), which we term the espA activating region
      (EAR). The EAR contains one of the known binding sites for EspR, providing the
      first in vivo evidence that transcriptional activation at the espA promoter
      occurs by EspR binding to the EAR and looping out DNA between this site and the
      promoter. Regulation of transcription of this operon thus takes place over long
      regions of the chromosome. This regulation may differ in some members of the M.
      tuberculosis complex, including Mycobacterium bovis, since deletions of the
      intergenic region have removed the upstream sequence containing the EAR,
      resulting in lowered espA expression. Consequent differences in expression of ESX
      1 in these bacteria may contribute to their various pathologies and host ranges.
      The virulence-critical nature of this operon means that transcription factors
      controlling its expression are possible drug targets.

PMID- 22389482
TI  - The variable subdomain of Escherichia coli SecA functions to regulate SecA ATPase
      activity and ADP release.
AB  - Bacterial SecA proteins can be categorized by the presence or absence of a
      variable subdomain (VAR) located within nucleotide-binding domain II of the SecA
      DEAD motor. Here we show that VAR is dispensable for SecA function, since the VAR
      deletion mutant secADelta519-547 displayed a wild-type rate of cellular growth
      and protein export. Loss or gain of VAR is extremely rare in the history of
      bacterial evolution, indicating that it appears to contribute to secA function
      within the relevant species in their natural environments. VAR removal also
      results in additional secA phenotypes: azide resistance (Azi(r)) and suppression
      of signal sequence defects (PrlD). The SecADelta(519-547) protein was found to be
      modestly hyperactive for SecA ATPase activities and displayed an accelerated rate
      of ADP release, consistent with the biochemical basis of azide resistance. Based
      on our findings, we discuss models whereby VAR allosterically regulates SecA DEAD
      motor function at SecYEG.

PMID- 22389483
TI  - RNA-Seq and RNA immunoprecipitation analyses of the transcriptome of Streptomyces
      coelicolor identify substrates for RNase III.
AB  - RNase III is a key enzyme in the pathways of RNA degradation and processing in
      bacteria and has been suggested as a global regulator of antibiotic production in
      Streptomyces coelicolor. Using RNA-Seq, we have examined the transcriptomes of S.
      coelicolor M145 and an RNase III (rnc)-null mutant of that strain. RNA
      preparations with reduced levels of structural RNAs were prepared by subtractive
      hybridization prior to RNA-Seq analysis. We initially identified 7,800
      transcripts of known and putative protein-coding genes in M145 and the null
      mutant, JSE1880, along with transcripts of 21 rRNA genes and 65 tRNA genes.
      Approximately 3,100 of the protein-coding transcripts were categorized as low
      abundance transcripts. For further analysis, we selected those transcripts of
      known and putative protein-coding genes whose levels changed by >= 2-fold between
      the two S. coelicolor strains and organized those transcripts into 16 functional
      categories. We refined our analysis by performing RNA immunoprecipitation of the
      mRNA preparation from JSE1880 using a mutant RNase III protein that binds to
      transcripts but does not cleave them. This analysis identified ca. 800
      transcripts that were enriched in the RNA immunoprecipitates, including 28
      transcripts whose levels also changed by >= 2-fold in the RNA-Seq analysis. We
      compare our results with those obtained by microarray analysis of the S.
      coelicolor transcriptome and with studies describing the characterization of
      small noncoding RNAs. We have also used the RNA immunoprecipitation results to
      identify new substrates for RNase III cleavage.

PMID- 22389484
TI  - Characterization of the structurally diverse N-linked glycans of Campylobacter
      species.
AB  - The Gram-negative bacterium Campylobacter jejuni encodes an extensively
      characterized N-linked protein glycosylation system that modifies many surface
      proteins with a heptasaccharide glycan. In C. jejuni, the genes that encode the
      enzymes required for glycan biosynthesis and transfer to protein are located at a
      single pgl gene locus. Similar loci are also present in the genome sequences of
      all other Campylobacter species, although variations in gene content and
      organization are evident. In this study, we have demonstrated that only
      Campylobacter species closely related to C. jejuni produce glycoproteins that
      interact with both a C. jejuni N-linked-glycan-specific antiserum and a lectin
      known to bind to the C. jejuni N-linked glycan. In order to further investigate
      the structure of Campylobacter N-linked glycans, we employed an in vitro peptide
      glycosylation assay combined with mass spectrometry to demonstrate that
      Campylobacter species produce a range of structurally distinct N-linked glycans
      with variations in the number of sugar residues (penta-, hexa-, and
      heptasaccharides), the presence of branching sugars, and monosaccharide content.
      These data considerably expand our knowledge of bacterial N-linked glycan
      structure and provide a framework for investigating the role of
      glycosyltransferases and sugar biosynthesis enzymes in glycoprotein biosynthesis
      with practical implications for synthetic biology and glycoengineering.

PMID- 22389485
TI  - Characterization of the flavonoid-responsive regulator FrrA and its binding
      sites.
AB  - Previous microarray analyses revealed that in Bradyrhizobium japonicum, about 100
      genes are induced by genistein, an isoflavonoid secreted by soybean. This
      includes the three genes freC, freA, and freB (systematic designations bll4319,
      bll4320, and bll4321), which are likely to form a genistein-, daidzein-, and
      coumestrol-inducible operon and to encode a multidrug efflux system. Upstream of
      freCAB and in the opposite orientation, FrrA (systematic designation Blr4322),
      which has similarity to TetR-type regulators, is encoded. A deletion of frrA
      leads to increased expression of freB in the absence of an inducer. We identified
      the correct translational start codon of frrA and showed that the gene is
      inducible by genistein and daidzein. The protein, which was heterologously
      expressed and purified from Escherichia coli, binds to two palindrome-like DNA
      elements (operator A and operator B), which are located in the intergenic region
      between freC and frrA. The replacement of several nucleotides or the insertion of
      additional spacer nucleotides prevented binding. Binding of FrrA was also
      affected by the addition of genistein. By mapping the transcription start sites,
      we found that operator A covers the transcriptional start site of freC and
      operator B is probably located between the -35 regions of the two divergently
      oriented genes. Operator A seems to be conserved in a few similar gene
      constellations in other proteobacteria. Our data indicate that in B. japonicum,
      besides NodD1 (the LysR family) and NodVW (a two-component response regulator), a
      third regulator type (a TetR family member) which responds to the plant signal
      molecules genistein and daidzein exists.

PMID- 22389486
TI  - Identification and characterization of a putative arginine kinase homolog from
      Myxococcus xanthus required for fruiting body formation and cell differentiation.
AB  - Arginine kinases catalyze the reversible transfer of a high-energy phosphoryl
      group from ATP to l-arginine to form phosphoarginine, which is used as an energy
      buffer in insects, crustaceans, and some unicellular organisms. It plays an
      analogous role to that of phosphocreatine in vertebrates. Recently, putative
      arginine kinases were identified in several bacterial species, including the
      social Gram-negative soil bacterium Myxococcus xanthus. It is still unclear what
      role these proteins play in bacteria and whether they have evolved to acquire
      novel functions in the species in which they are found. In this study, we
      biochemically purified and characterized a putative M. xanthus arginine kinase,
      Ark, and demonstrated that it has retained the ability to catalyze the
      phosphorylation of arginine by using ATP. We also constructed a null mutation in
      the ark gene and demonstrated its role in both certain stress responses and
      development.

PMID- 22389487
TI  - TprC/D (Tp0117/131), a trimeric, pore-forming rare outer membrane protein of
      Treponema pallidum, has a bipartite domain structure.
AB  - Identification of Treponema pallidum rare outer membrane proteins (OMPs) has been
      a longstanding objective of syphilis researchers. We recently developed a
      consensus computational framework that employs a battery of cellular localization
      and topological prediction tools to generate ranked clusters of candidate rare
      OMPs (D. L. Cox et al., Infect. Immun. 78:5178-5194, 2010). TP0117/TP0131
      (TprC/D), a member of the T. pallidum repeat (Tpr) family, was a highly ranked
      candidate. Circular dichroism, heat modifiability by SDS-PAGE, Triton X-114 phase
      partitioning, and liposome incorporation confirmed that full-length, recombinant
      TprC (TprC(Fl)) forms a beta-barrel capable of integrating into lipid bilayers.
      Moreover, TprC(Fl) increased efflux of terbium-dipicolinic acid complex from
      large unilamellar vesicles and migrated as a trimer by blue-native PAGE. We found
      that in T. pallidum, TprC is heat modifiable, trimeric, expressed in low
      abundance, and, based on proteinase K accessibility and opsonophagocytosis
      assays, surface exposed. From these collective data, we conclude that TprC is a
      bona fide rare OMP as well as a functional ortholog of Escherichia coli OmpF. We
      also discovered that TprC has a bipartite architecture consisting of a soluble N
      terminal portion (TprC(N)), presumably periplasmic and bound directly or
      indirectly to peptidoglycan, and a C-terminal beta-barrel (TprC(C)). Syphilitic
      rabbits generate antibodies exclusively against TprC(C), while secondary syphilis
      patients fail to mount a detectable antibody response against either domain. The
      syphilis spirochete appears to have resolved a fundamental dilemma arising from
      its extracellular lifestyle, namely, how to enhance OM permeability without
      increasing its vulnerability to the antibody-mediated defenses of its natural
      human host.

PMID- 22389488
TI  - Characterization of the response to zinc deficiency in the cyanobacterium
      Anabaena sp. strain PCC 7120.
AB  - Zur regulators control zinc homeostasis by repressing target genes under zinc
      sufficient conditions in a wide variety of bacteria. This paper describes how
      part of a survey of duplicated genes led to the identification of the open
      reading frame all2473 as the gene encoding the Zur regulator of the
      cyanobacterium Anabaena sp. strain PCC 7120. All2473 binds to DNA in a zinc
      dependent manner, and its DNA-binding sequence was characterized, which allowed
      us to determine the relative contribution of particular nucleotides to Zur
      binding. A zur mutant was found to be impaired in the regulation of zinc
      homeostasis, showing sensitivity to elevated concentrations of zinc but not other
      metals. In an effort to characterize the Zur regulon in Anabaena, 23 genes
      containing upstream putative Zur-binding sequences were identified and found to
      be regulated by Zur. These genes are organized in six single transcriptional
      units and six operons, some of them containing multiple Zur-regulated promoters.
      The identities of genes of the Zur regulon indicate that Anabaena adapts to
      conditions of zinc deficiency by replacing zinc metalloproteins with paralogues
      that fulfill the same function but presumably with a lower zinc demand, and with
      inducing putative metallochaperones and membrane transport systems likely being
      involved in the scavenging of extracellular zinc, including plasma membrane ABC
      transport systems and outer membrane TonB-dependent receptors. Among the Zur
      regulated genes, the ones showing the highest induction level encode proteins of
      the outer membrane, suggesting a primary role for components of this cell
      compartment in the capture of zinc cations from the extracellular medium.

PMID- 22389489
TI  - Identification of the HetR recognition sequence upstream of hetZ in Anabaena sp.
      strain PCC 7120.
AB  - HetR is the master regulator of heterocyst differentiation in Anabaena sp. strain
      PCC 7120 and has been found to specifically bind to an inverted-repeat-containing
      region upstream of hetP, a heterocyst differentiation gene. However, no such
      inverted-repeat sequence can be found in promoters of other genes in the genome.
      hetZ is a gene involved in early heterocyst differentiation. As shown with the
      gfp reporter gene, transcription from P(hetZ) was correlated to the expression
      level of hetR and inhibition by RGSGR, the pentapeptide derived from the C
      terminus of PatS. As detected by electrophoretic mobility shift assay, a
      recombinant HetR showed specific binding to the region upstream of hetZ, and the
      binding was inhibited by RGSGR. Tests of a series of the upstream fragments
      delimited the HetR-binding site to a 40-bp region that shows similarity to that
      upstream of hetP. The introduction of substitutions of bases conserved in the two
      HetR-binding sites showed that at least 12 bases are required for recognition by
      HetR. Deletion of a 51-bp region containing the HetR-binding site completely
      eliminated the transcription activity of P(hetZ). Based on the HetR recognition
      sequence of hetZ, those upstream of hetR and patA are proposed.

PMID- 22389490
TI  - 20-Hydroxyeicosatetraenoic acid (20-HETE) is a novel activator of transient
      receptor potential vanilloid 1 (TRPV1) channel.
AB  - TRPV1 is a member of the transient receptor potential ion channel family and is
      gated by capsaicin, the pungent component of chili pepper. It is expressed
      predominantly in small diameter peripheral nerve fibers and is activated by
      noxious temperatures >42  degrees C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is
      a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid
      arachidonic acid. It is a powerful vasoconstrictor and has structural
      similarities with other TRPV1 agonists, e.g. the hydroperoxyeicosatetraenoic acid
      12-HPETE, and we hypothesized that it may be an endogenous ligand for TRPV1 in
      sensory neurons innervating the vasculature. Here, we demonstrate that 20-HETE
      both activates and sensitizes mouse and human TRPV1, in a kinase-dependent
      manner, involving the residue Ser(502) in heterologously expressed hTRPV1, at
      physiologically relevant concentrations.

PMID- 22389491
TI  - Chondroitin sulfate proteoglycans down-regulate spine formation in cortical
      neurons by targeting tropomyosin-related kinase B (TrkB) protein.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular
      matrix that inhibit axonal sprouting and experience-dependent plasticity.
      Although protein-tyrosine phosphatase sigma (PTPsigma) has been proven to be a
      receptor for CSPGs, its downstream signaling has remained a mystery. Here, we
      show that CSPGs target and dephosphorylate tropomyosin-related kinase B, the
      receptor of brain-derived neurotrophic factor (BDNF), via PTPsigma in embryonic
      cortical neurons in vitro. Whereas BDNF promoted dendritic spine formation in
      embryonic cortical neurons, CSPGs abolished the effects of BDNF and eliminated
      existing dendritic spines when BDNF was present. The latter effect was dependent
      on the p75 receptor, presumably because BDNF binding to the p75 receptor elicits
      elimination of dendritic spines. These results suggest that the inhibitory
      activity of CSPGs on dendritic spine formation operates through the targeting of
      neurotrophins at the receptor level.

PMID- 22389492
TI  - Protein Gq modulates termination of phototransduction and prevents retinal
      degeneration.
AB  - Appropriate termination of the phototransduction cascade is critical for
      photoreceptors to achieve high temporal resolution and to prevent excessive
      Ca(2+)-induced cell toxicity. Using a genetic screen to identify defective
      photoresponse mutants in Drosophila, we isolated and identified a novel Galpha(q)
      mutant allele, which has defects in both activation and deactivation. We revealed
      that G(q) modulates the termination of the light response and that
      metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1)
      binding, which mediates the deactivation of metarhodopsin. We further showed that
      the Galpha(q) mutant undergoes light-dependent retinal degeneration, which is due
      to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the
      roles of G(q) in mediating photoresponse termination and in preventing retinal
      degeneration. This pathway may represent a general rapid feedback regulation of G
      protein-coupled receptor signaling.

PMID- 22389493
TI  - Increased atherosclerosis and endothelial dysfunction in mice bearing
      constitutively deacetylated alleles of Foxo1 gene.
AB  - Complications of atherosclerosis are the leading cause of death of patients with
      type 2 (insulin-resistant) diabetes. Understanding the mechanisms by which
      insulin resistance and hyperglycemia contribute to atherogenesis in key target
      tissues (liver, vessel wall, hematopoietic cells) can assist in the design of
      therapeutic approaches. We have shown that hyperglycemia induces FoxO1
      deacetylation and that targeted knock-in of alleles encoding constitutively
      deacetylated FoxO1 in mice (Foxo1(KR/KR)) improves hepatic lipid metabolism and
      decreases macrophage inflammation, setting the stage for a potential anti
      atherogenic effect of this mutation. Surprisingly, we report here that when
      Foxo1(KR/KR) mice are intercrossed with low density lipoprotein receptor knock
      out mice (Ldlr(-/-)), they develop larger aortic root atherosclerotic lesions
      than Ldlr(-/-) controls despite lower plasma cholesterol and triglyceride levels.
      The phenotype is unaffected by transplanting bone marrow from Ldlr(-/-) mice into
      Foxo1(KR/KR) mice, indicating that it is independent of hematopoietic cells and
      suggesting that the primary lesion in Foxo1(KR/KR) mice occurs in the vessel
      wall. Experiments in isolated endothelial cells from Foxo1(KR/KR) mice indicate
      that deacetylation favors FoxO1 nuclear accumulation and exerts target gene
      specific effects, resulting in higher Icam1 and Tnfalpha expression and increased
      monocyte adhesion. The data indicate that FoxO1 deacetylation can promote
      vascular endothelial changes conducive to atherosclerotic plaque formation.

PMID- 22389494
TI  - Coming into view: eukaryotic iron chaperones and intracellular iron delivery.
AB  - Eukaryotic cells contain hundreds of metalloproteins, and ensuring that each
      protein receives the correct metal ion is a critical task for cells. Recent work
      in budding yeast and mammalian cells has uncovered a system of iron delivery
      operating in the cytosolic compartment that involves monothiol glutaredoxins,
      which bind iron in the form of iron-sulfur clusters, and poly(rC)-binding
      proteins, which bind Fe(II) directly. In yeast cells, cytosolic monothiol
      glutaredoxins are required for the formation of heme and iron-sulfur clusters and
      the metallation of some non-heme iron enzymes. Poly(rC)-binding proteins can act
      as iron chaperones, delivering iron to target non-heme enzymes through direct
      protein-protein interactions. Although the molecular details have yet to be
      explored, these proteins, acting independently or together, may represent the
      basic cellular machinery for intracellular iron delivery.

PMID- 22389495
TI  - Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and
      metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells.
AB  - Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins
      (RCAN1s) have both protective and harmful effects and are implicated in common
      human pathologies. The mechanisms by which RCAN1s function, however, remain
      poorly understood. We identify RCAN1s as regulators of mitochondrial autophagy
      (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic
      degradation of mitochondria. The mechanisms of such degradation involve the
      adenine nucleotide translocator and mitochondrial permeability transition pore
      opening. We also demonstrate that RCAN1-1L induction can shift cellular
      bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very
      little effect on cell division, whereas it has a cumulative negative effect on
      cell survival. These results shed the light on mechanisms by which RCAN1s can
      protect or harm cells and by which they may operate in human pathologies. They
      also suggest that RCAN1s are important players in autophagy and such elusive
      phenomena as the mitochondrial permeability transition pore.

PMID- 22389496
TI  - Mammalian siderophores, siderophore-binding lipocalins, and the labile iron pool.
AB  - Bacteria use tight-binding, ferric-specific chelators called siderophores to
      acquire iron from the environment and from the host during infection; animals use
      proteins such as transferrin and ferritin to transport and store iron. Recently,
      candidate compounds that could serve endogenously as mammalian siderophore
      equivalents have been identified and characterized through associations with
      siderocalin, the only mammalian siderophore-binding protein currently known.
      Siderocalin, an antibacterial protein, acts by sequestering iron away from
      infecting bacteria as siderophore complexes. Candidate endogenous siderophores
      include compounds that only effectively transport iron as ternary complexes with
      siderocalin, explaining pleiotropic activities in normal cellular processes and
      specific disease states.

PMID- 22389497
TI  - Structure-function relationships in [FeFe]-hydrogenase active site maturation.
AB  - Since the discovery that, despite the active site complexity, only three gene
      products suffice to obtain active recombinant [FeFe]-hydrogenase, significant
      light has been shed on this process. Both the source of the CO and CN(-) ligands
      to iron and the assembly site of the catalytic subcluster are known, and an apo
      structure of HydF has been published recently. However, the nature of the
      substrate(s) for the synthesis of the bridging dithiolate ligand to the
      subcluster remains to be established. From both spectroscopy and model chemistry,
      it is predicted that an amine function in this ligand plays a central role in
      catalysis, acting as a base in the heterolytic cleavage of hydrogen.

PMID- 22389498
TI  - Copper homeostasis at the host-pathogen interface.
AB  - The trace element copper is indispensable for all aerobic life forms. Its ability
      to cycle between two oxidation states, Cu(1+) and Cu(2+), has been harnessed by a
      wide array of metalloenzymes that catalyze electron transfer reactions. The
      metabolic needs for copper are sustained by a complex series of transporters and
      carrier proteins that regulate its intracellular accumulation and distribution in
      both pathogenic microbes and their animal hosts. However, copper is also
      potentially toxic due in part to its ability to generate reactive oxygen species.
      Recent studies suggest that the macrophage phagosome accumulates copper during
      bacterial infection, which may constitute an important mechanism of killing.
      Bacterial countermeasures include the up-regulation of copper export and
      detoxification genes during infection, which studies suggest are important
      determinants of virulence. In this minireview, we summarize recent developments
      that suggest an emerging role for copper as an unexpected component in
      determining the outcome of host-pathogen interactions.

PMID- 22389499
TI  - Metal transport across biomembranes: emerging models for a distinct chemistry.
AB  - Transition metals are essential components of important biomolecules, and their
      homeostasis is central to many life processes. Transmembrane transporters are key
      elements controlling the distribution of metals in various compartments. However,
      due to their chemical properties, transition elements require transporters with
      different structural-functional characteristics from those of alkali and alkali
      earth ions. Emerging structural information and functional studies have revealed
      distinctive features of metal transport. Among these are the relevance of
      multifaceted events involving metal transfer among participating proteins, the
      importance of coordination geometry at transmembrane transport sites, and the
      presence of the largely irreversible steps associated with vectorial transport.
      Here, we discuss how these characteristics shape novel transition metal ion
      transport models.

PMID- 22389500
TI  - Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated
      protein: PKA-dependent phosphoregulation of microtubule binding affinity.
AB  - Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) is a brain specific and F
      actin-binding protein. We recently demonstrated that IP(3)K-A modulates a
      structural reorganization of dendritic spines through F-actin remodeling, which
      is required for synaptic plasticity and memory formation in brain. However,
      detailed functions of IP(3)K-A and its regulatory mechanisms involved in the
      neuronal cytoskeletal dynamics still remain unknown. In the present study, we
      identified tubulin as a candidate of IP(3)K-A-binding protein through proteomic
      screening. By various in vitro and in vivo approaches, we demonstrated that
      IP(3)K-A was a novel microtubule-associated protein (MAP), and the N terminus of
      IP(3)K-A was a critical region for direct binding to tubulin in dendritic shaft
      of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP(3)K-A,
      leading to a significant reduction of microtubule binding affinity. These results
      suggest that PKA-dependent phosphorylation and microtubule binding of IP(3)K-A
      are involved in its regulatory mechanism for activity-dependent neuronal events
      such as local calcium signaling and its synaptic targeting.

PMID- 22389501
TI  - Involvement of nuclear factor kappaB (NF-kappaB) signaling pathway in regulation
      of cardiac G protein-coupled receptor kinase 5 (GRK5) expression.
AB  - G protein-coupled receptor kinase 5 (GRK5) plays a key role in cardiac signaling
      regulation, and its expression is increased in heart failure. Recently, increased
      expression of GRK5 in the myocardium of mice has been shown to be detrimental in
      the setting of pressure-overload hypertrophy. The ubiquitous nuclear
      transcription factor kappaB (NF-kappaB) is involved in the regulation of numerous
      genes in various tissues, and activation of NF-kappaB has been shown to be
      associated with heart disease. Here, we investigated the role of NF-kappaB
      signaling in the regulation of the GRK5 gene and expression of this kinase in
      cardiomyocytes. First, in analyzing the 5'-flanking DNA of GRK5, the presence of
      a potential NF-kappaB binding site was observed in the promoter region. Phorbol
      myristate acetate, a known stimulator of NF-kappaB, increased the levels of GRK5
      in myocytes whereas treatment of cells with N-acetyl cysteine, a known inhibitor
      of NF-kappaB, or with SC 514, an inhibitor of IkappaB kinase 2 decreased GRK5.
      Utilizing EMSA or ChIP assays, we found that both p50 and p65 NF-kappaB could
      interact with the promoter of GRK5 following myocytes NF-kappaB activation.
      Importantly, short interfering RNA (siRNA)-mediated loss of p65 in myocytes
      decreased the stimulated increased levels of GRK5 mRNA and protein. Finally,
      adenovirus-mediated overexpression of a dominant-negative IkappaBalpha in
      myocytes inhibited the levels of GRK5. Taken together, our study demonstrates
      that NF-kappaB plays a critical role in the regulation of GRK5 transcription in
      myocytes and that this may translate to the significant expression changes seen
      in heart disease.

PMID- 22389502
TI  - Hypertrophy in skeletal myotubes induced by junctophilin-2 mutant, Y141H,
      involves an increase in store-operated Ca2+ entry via Orai1.
AB  - Junctophilins (JPs) play an important role in the formation of junctional
      membrane complexes (JMC) in striated muscle by physically linking the transverse
      tubule and sarcoplasmic reticulum (SR) membranes. Researchers have found five JP2
      mutants in humans with hypertrophic cardiomyopathy. Among these, Y141H and S165F
      are associated with severely altered Ca(2+) signaling in cardiomyocytes. We
      previously reported that S165F also induced both hypertrophy and altered
      intracellular Ca(2+) signaling in mouse skeletal myotubes. In the present study,
      we attempted to identify the dominant-negative role(s) of Y141H in primary mouse
      skeletal myotubes. Consistent with S165F, Y141H led to hypertrophy and altered
      Ca(2+) signaling (a decrease in the gain of excitation-contraction coupling and
      an increase in the resting level of myoplasmic Ca(2+)). However, unlike S165F,
      neither ryanodine receptor 1-mediated Ca(2+) release from the SR nor the
      phosphorylation of the mutated JP2 by protein kinase C was related to the altered
      Ca(2+) signaling by Y141H. Instead, abnormal JMC and increased SOCE via Orai1
      were found, suggesting that the hypertrophy caused by Y141H progressed
      differently from S165F. Therefore JP2 can be linked to skeletal muscle
      hypertrophy via various Ca(2+) signaling pathways, and SOCE could be one of the
      causes of altered Ca(2+) signaling observed in muscle hypertrophy.

PMID- 22389503
TI  - Intramolecular fluorescence resonance energy transfer (FRET) sensors of the
      orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
AB  - Intramolecular fluorescence resonance energy transfer (FRET) sensors able to
      detect changes in distance or orientation between the 3rd intracellular loop and
      C-terminal tail of the human orexin OX(1) and OX(2) G protein-coupled receptors
      following binding of agonist ligands were produced and expressed stably. These
      were directed to the plasma membrane and, despite the substantial sequence
      alterations introduced, in each case were able to elevate [Ca(2+)](i), promote
      phosphorylation of the ERK1/2 MAP kinases and become internalized effectively
      upon addition of the native orexin peptides. Detailed characterization of the
      OX(1) sensor demonstrated that it was activated with rank order of potency orexin
      A > orexin B > orexin A 16-33, that it bound antagonist ligands with affinity
      similar to the wild-type receptor, and that mutation of a single residue, D203A,
      greatly reduced the binding and function of orexin A but not antagonist ligands.
      Addition of orexin A to individual cells expressing an OX(1) sensor resulted in a
      time- and concentration-dependent reduction in FRET signal consistent with mass
      action and potency/affinity estimates for the peptide. Compared with the response
      kinetics of a muscarinic M(3) acetylcholine receptor sensor upon addition of
      agonist, response of the OX(1) and OX(2) sensors to orexin A was slow, consistent
      with a multistep binding and activation process. Such sensors provide means to
      assess the kinetics of receptor activation and how this may be altered by
      mutation and sequence variation of the receptors.

PMID- 22389504
TI  - The cell adhesion molecule neuroplastin-65 is a novel interaction partner of
      gamma-aminobutyric acid type A receptors.
AB  - gamma-Aminobutyric acid type A (GABA(A)) receptors are pentameric ligand-gated
      ion channels that mediate fast inhibition in the central nervous system.
      Depending on their subunit composition, these receptors exhibit distinct
      pharmacological properties and differ in their ability to interact with proteins
      involved in receptor anchoring at synaptic or extra-synaptic sites. Whereas
      GABA(A) receptors containing alpha1, alpha2, or alpha3 subunits are mainly
      located synaptically where they interact with the submembranous scaffolding
      protein gephyrin, receptors containing alpha5 subunits are predominantly found
      extra-synaptically and seem to interact with radixin for anchorage. Neuroplastin
      is a cell adhesion molecule of the immunoglobulin superfamily that is involved in
      hippocampal synaptic plasticity. Our results reveal that neuroplastin and GABA(A)
      receptors can be co-purified from rat brain and exhibit a direct physical
      interaction as demonstrated by co-precipitation and Forster resonance energy
      transfer (FRET) analysis in a heterologous expression system. The brain-specific
      isoform neuroplastin-65 co-localizes with GABA(A) receptors as shown in brain
      sections as well as in neuronal cultures, and such complexes can either contain
      gephyrin or be devoid of gephyrin. Neuroplastin-65 specifically co-localizes with
      alpha1 or alpha2 but not with alpha3 subunits at GABAergic synapses. In addition,
      neuroplastin-65 also co-localizes with GABA(A) receptor alpha5 subunits at extra
      synaptic sites. Down-regulation of neuroplastin-65 by shRNA causes a loss of
      GABA(A) receptor alpha2 subunits at GABAergic synapses. These results suggest
      that neuroplastin-65 can co-localize with a subset of GABA(A) receptor subtypes
      and might contribute to anchoring and/or confining GABA(A) receptors to
      particular synaptic or extra-synaptic sites, thus affecting receptor mobility and
      synaptic strength.

PMID- 22389505
TI  - Sphingosine 1-phosphate (S1P) regulates glucose-stimulated insulin secretion in
      pancreatic beta cells.
AB  - Recent studies suggest that sphingolipid metabolism is altered during type 2
      diabetes. Increased levels of the sphingolipid ceramide are associated with
      insulin resistance. However, a role for sphingolipids in pancreatic beta cell
      function, or insulin production, and release remains to be established. Our
      studies in MIN6 cells and mouse pancreatic islets demonstrate that glucose
      stimulates an intracellular rise in the sphingolipid, sphingosine 1-phosphate
      (S1P), whereas the levels of ceramide and sphingomyelin remain unchanged. The
      increase in S1P levels by glucose is due to activation of sphingosine kinase 2
      (SphK2). Interestingly, rises in S1P correlate with increased glucose-stimulated
      insulin secretion (GSIS). Decreasing S1P levels by treatment of MIN6 cells or
      primary islets with the sphingosine kinase inhibitor reduces GSIS. Moreover,
      knockdown of SphK2 alone results in decreased GSIS, whereas knockdown of the S1P
      phosphatase, Sgpp1, leads to a rise in GSIS. Treatment of mice with the
      sphingosine kinase inhibitor impairs glucose disposal due to decreased plasma
      insulin levels. Altogether, our data suggest that glucose activates SphK2 in
      pancreatic beta cells leading to a rise in S1P levels, which is important for
      GSIS.

PMID- 22389506
TI  - Novel insight into KLF4 proteolytic regulation in estrogen receptor signaling and
      breast carcinogenesis.
AB  - Kruppel-like factor 4 (KLF4), a zinc finger-containing transcriptional factor, is
      a pivotal regulator of cellular fate. KLF4 has attracted considerable attention
      for its opposing effect in carcinogenesis as tumor suppressor (e.g. colorectal
      cancer) or oncoprotein (e.g. breast cancer), depending on tissue context, with
      the underlying mechanism remaining largely unknown. Here we report that KLF4
      mediates estrogen signaling in breast cancer formation. Accumulation of KLF4 by
      inhibiting its turnover triggers estrogen-induced transactivation. We identified
      Von Hippel-Lindau, pVHL, as the protein that governs KLF4 turnover in breast
      cancer cells and demonstrated that estrogen-induced down-regulation of pVHL
      facilitates accumulation of KLF4. We provide mechanistic insights into KLF4
      steady-state degradation as well as its elevation in the presence of estrogen and
      show that elevated levels of pVHL or depletion of KLF4 attenuates the estrogen
      induced transactivation and cell growth. Finally, immunohistochemical staining
      revealed reduced concentration of pVHL and accumulation of KLF4 in breast cancer
      tissues. We thus propose that suppression of pVHL in response to estrogen
      signaling results in elevation of KLF4, which mediates estrogen-induced mitogenic
      effect.

PMID- 22389507
TI  - Thematic minireview series: Metals in Biology 2012.
AB  - Metals are present in about one-half of the protein structures available and also
      have critical roles in nucleic acid biochemistry. This prologue introduces the
      fourth of the Thematic Minireview Series on Metals in Biology, which deals with
      several topics involving iron, manganese, copper, and other metals. The six
      minireviews discuss metal transport and intracellular homeostasis, including
      chaperones and siderophores, maturation of the diiron active sites in
      hydrogenases, the balance between manganese and iron, and copper homeostasis
      relevant to pathogens.

PMID- 22389511
TI  - HPV 18 prevalence in oral mucosa diagnosed with verrucous leukoplakia:
      cytological and molecular analysis.

PMID- 22389512
TI  - Predictors of human epidermal growth factor receptor 2 fluorescence in-situ
      hybridisation amplification in immunohistochemistry score 2+ infiltrating breast
      cancer: a single institution analysis.
AB  - AIMS: Eligibility for anti-human epidermal growth factor receptor 2 (HER2)
      treatments in breast cancer requires a correct HER2 status assessment. Testing
      guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored
      as 2+ by immunohistochemistry. This study investigates the correlation between
      pathological features and FISH amplification in HER2 2+ breast cancer cases.
      METHODS: 480 HER2 2+ breast cancer samples were included. The association between
      tumour grade, hormone receptor status, proliferation index (Ki67) and FISH
      amplification, using both US Food and Drug Administration (ratio >=2) and
      American Society of Clinical Oncologists/College of American Pathologists cut
      offs (ratio >2.2) was evaluated. RESULTS: 90.2% of the samples were hormone
      receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a
      Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%),
      268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio >=2.0) and
      20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1
      2 tumours: 34% versus 18% (ratio >=2.0, p<0.001) and 27% versus 9% (ratio >2.2,
      p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates
      than low Ki67 samples: 31% versus 21% (ratio >=2.0, p=0.022) and 25% versus 12%
      (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case
      of grade 3 and high Ki67 with both cut-offs. CONCLUSIONS: In this study, high
      tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2
      2+ breast cancer samples.

PMID- 22389513
TI  - Nuclear survivin is associated with cell proliferative advantage in uterine
      cervical carcinomas during radiation therapy.
AB  - BACKGROUND: Although the anticancer effects of radiation therapy for patients
      with uterine cervical squamous cell carcinoma (U-SCC) are widely acknowledged,
      little is known about the resultant morphological alterations in tumour tissue
      kinetics. AIMS: To make a detailed assessment of possible roles of survivin
      expression in apoptosis and cell proliferation in U-SCC during radiation therapy.
      METHODS: 181 biopsy specimens from 55 consecutive U-SCCs of patients receiving
      radiation therapy were studied using a combined morphological (apoptosis) and
      immunohistochemical (MIB-1 and survivin) approach. The intracellular distribution
      of various splice variants of the survivin gene was also examined. RESULTS:
      Tumour cell proliferation, determined as MIB-1 labelling indices (LIs), as well
      as nuclear survivin (N-Surv) LIs, were inversely correlated with irradiation
      dosage, in contrast to relatively minor changes in apoptotic indices, suggesting
      a shift in tumour tissue kinetics towards a relative predominance of cell
      deletion. In addition, the low N-Sur LI category showed significant stepwise
      decrease in MIB-1 LIs during therapy, in contrast to no changes in the high
      category. Exogenous overexpression of three variants of the survivin gene
      resulted in different expression patterns, showing cytoplasmic staining with or
      without dot formation for survivin and survivin-2B and distinct nuclear
      accumulation for survivin-deled exon 3 (Ex3). CONCLUSIONS: Results showed that
      nuclear survivin, including survivin itself and the survivin-Ex3 splice variants,
      may participate in modulation of altered cell kinetics of U-SCC during radiation
      therapy.

PMID- 22389508
TI  - Activation of mitochondrial calcium-independent phospholipase A2gamma
      (iPLA2gamma) by divalent cations mediating arachidonate release and production of
      downstream eicosanoids.
AB  - Calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) (PNPLA8) is the
      predominant phospholipase activity in mammalian mitochondria. However, the
      chemical mechanisms that regulate its activity are unknown. Here, we utilize
      iPLA(2)gamma gain of function and loss of function genetic models to demonstrate
      the robust activation of iPLA(2)gamma in murine myocardial mitochondria by Ca(2+)
      or Mg(2+) ions. Calcium ion stimulated the production of 2-arachidonoyl
      lysophosphatidylcholine (2-AA-LPC) from 1-palmitoyl-2-[(14)C]arachidonoyl-sn
      glycero-3-phosphocholine during incubations with wild-type heart mitochondrial
      homogenates. Furthermore, incubation of mitochondrial homogenates from transgenic
      myocardium expressing iPLA(2)gamma resulted in 13- and 25-fold increases in the
      initial rate of radiolabeled 2-AA-LPC and arachidonic acid (AA) production,
      respectively, in the presence of calcium ion. Mass spectrometric analysis of the
      products of calcium-activated hydrolysis of endogenous mitochondrial
      phospholipids in transgenic iPLA(2)gamma mitochondria revealed the robust
      production of AA, 2-AA-LPC, and 2-docosahexaenoyl-LPC that was over 10-fold
      greater than wild-type mitochondria. The mechanism-based inhibitor (R)-(E)-6
      (bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL) (iPLA(2)gamma
      selective), but not its enantiomer, (S)-BEL (iPLA(2)beta selective) or
      pyrrolidine (cytosolic PLA(2)alpha selective), markedly attenuated Ca(2+)
      dependent fatty acid release and polyunsaturated LPC production. Moreover, Ca(2+)
      induced iPLA(2)gamma activation was accompanied by the production of downstream
      eicosanoid metabolites that were nearly completely ablated by (R)-BEL or by
      genetic ablation of iPLA(2)gamma. Intriguingly, Ca(2+)-induced iPLA(2)gamma
      activation was completely inhibited by long-chain acyl-CoA (IC(50) ~20 MUm) as
      well as by a nonhydrolyzable acyl-CoA thioether analog. Collectively, these
      results demonstrate that mitochondrial iPLA(2)gamma is activated by divalent
      cations and inhibited by acyl-CoA modulating the generation of biologically
      active metabolites that regulate mitochondrial bioenergetic and signaling
      functions.

PMID- 22389514
TI  - High antiphospholipid antibody levels are associated with statin use and may
      reflect chronic endothelial damage in non-autoimmune thrombosis: cross-sectional
      study.
AB  - OBJECTIVE: Persistently elevated antiphospholipid antibodies and positive lupus
      anticoagulant (LAC) are associated with an increased risk of thrombosis. The
      objective of this study was to explore whether antiphospholipid antibody and/or
      LAC positivity were associated with the traditional risk factors for thrombosis
      or with medication use in patients without autoimmune diseases hospitalised with
      arterial or venous thrombosis. DESIGN: Cross-sectional study. SETTING: Montefiore
      Medical Center, a large urban tertiary care centre. PATIENTS: 270 patients (93
      with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non
      haemorrhagic stroke (cerebrovascular accident (CVA)) admitted between January
      2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who
      had LAC and antiphospholipid antibodies measured within 6 months from their index
      admission. Patients with lupus or antiphospholipid syndrome were excluded. MAIN
      OUTCOME MEASURES: The main dependent variable was antiphospholipid antibodies of
      40 units or greater (antiphospholipid antibody positivity) and/or LAC positivity.
      Independent variables were traditional thrombosis risk factors, statin use,
      aspirin use and warfarin use. RESULTS: 31 (11%) patients were LAC positive and/or
      antiphospholipid antibody positive. None of the traditional risk factors at the
      time of DVT/PE/CVA was associated with antiphospholipid antibody positivity.
      Current statin use was associated with an OR of 3.2 (95% CI 1.3 to 7.9, p=0.01)
      of antiphospholipid antibody positivity, adjusted for age, ethnicity and gender.
      Aspirin or warfarin use was not associated with antiphospholipid antibody levels.
      CONCLUSION: If statin therapy reflects the history of previous hyperlipidaemia,
      high levels of antiphospholipid antibodies may be a marker for earlier
      endothelial damage caused by hyperlipidaemia.

PMID- 22389515
TI  - The enduring effects of marital status on subsequent depressive symptoms among
      women: investigating the roles of psychological, social and financial resources.
AB  - OBJECTIVES: To investigate the mechanisms through which marital status exerts
      long-term effects on depressive symptoms among women and to evaluate the relative
      importance of psychological, social and financial resources in mediating this
      relationship. METHODS: Data came from 6107 female respondents to a nationally
      representative longitudinal data set from the USA (National Survey of Families
      and Households 1987-1988/1992-1994). Mediation was investigated using semi
      longitudinal structural equation modelling and bias-corrected bootstrapped CIs.
      Latent constructs with multiple indicators were used to measure depressive
      symptoms, primary and secondary social integration and self-esteem. RESULTS: The
      total effect of marital status on subsequent depressive symptoms was
      statistically significant for all marital statuses relative to those in first
      marriages controlling for age, education, race, number of children younger than 5
      in the household, T1 depressive symptoms and marital status transitions between
      waves; all groups experienced higher levels of depressive symptoms than those in
      first marriages. These effects were completely mediated for never-married women
      and partially mediated for separated/divorced, widowed and cohabiting women.
      Adjusted household income was the largest mediator for the separated/divorced,
      widowed and never-married, but primary social integration also played a role.
      Self-esteem was the only significant mediator for the remarried and cohabiting
      and was also important in explaining differences between the first-married and
      separated/divorced. CONCLUSION: This study demonstrates that the reasons why
      marital status has an influence on subsequent depressive symptoms varies
      depending on the specific marital status being compared with the married.

PMID- 22389516
TI  - Roles for a soybean RAV-like orthologue in shoot regeneration and
      photoperiodicity inferred from transgenic plants.
AB  - The soybean gene Glyma10g34760 appears to encode a RAV2-like transcription factor
      orthologue (DQ147914; hereafter GmRAV) based on sequence similarity. The gene is
      a member of the ERF/AP2 transcription factor family that has been shown to be
      increased in transcript abundance by cytokinins (CKs). Transgenic GmRAV
      overexpressing (-ox) tobacco plants exhibited increased CK signalling-related
      phenotypes including dwarfism, reduced apical dominance, extreme longevity,
      vigorous outgrowth of lateral buds, small and dark green leaves, reduced root
      growth, repressed flowering under both long- and short-day conditions, and
      altered sensitivity to daylength. In contrast, inhibition (-i) of GmRAV in
      soybean displayed the opposite phenotypic alterations which were consistent with
      defects in CK signalling. Phenotypes included earlier time of emergence; reduced
      numbers of branches, leaves, and flower buds; increased plant height; increased
      apical dominance; and earlier flowering and maturity. GmRAV-i soybean was less
      sensitive to cytokinin in hypocotyls and root growth inhibition assays. GmRAV-i
      soybean showed decreased frequency of adventious shoot formation in tissue
      culture in the presence of CKs, which might be attributed to the significantly
      decreased activities of CUC2, STM, and WUS involved in shoot meristem
      specification. GmRAV protein was localized in the nucleus in leaves. The GmRAV
      promoter-beta-glucuronidase (GUS) fusion was largely expressed in a meristematic
      region of the shoot apex, which was consistent with expressed sequence tag and
      microarray data. GmRAV was inferred to play a key role in CK and photoperiod
      signalling that subsequently regulated plant development.

PMID- 22389517
TI  - Improved Estimation of Oil, Linoleic and Oleic Acid and Seed Hull Fractions in
      Safflower by NIRS.
AB  - Near-infrared reflectance spectroscopy (NIRS) of intact seeds allows the non
      destructive estimation of seed quality parameters which is highly desirable in
      plant breeding. Together with yield, oil content and quality, a main aim in
      safflower (Carthamus tinctorius L.) breeding is the selection of genotypes with a
      low percentage of empty seeds even under cooler climates. We developed NIRS
      calibrations for seed oil content, oleic and linoleic acid content, the seed hull
      fraction and the percentage of empty seeds using seed meal and intact seeds. For
      the different calibrations 108-534 samples from a safflower breeding program with
      lines adapted to German conditions, were analyzed with reference analyses
      (Soxhlet, gas chromatography), and scanned by NIRS as intact seeds and seed meal.
      Calibration equations were developed and tested through cross validation. The
      coefficient of determination of the calibration (R(2)) for intact seeds ranged
      from 0.91(oil content), 0.90 (seed hull fraction), 0.84 (empty seeds), 0.73
      (linoleic acid) to 0.68 (oleic acid). The coefficient of determination of the
      cross validation was higher for seed meal than for intact seeds except for the
      parameter seed hull fraction. The results show that NIRS calibrations are
      applicable in safflower breeding programs for a fast screening.

PMID- 22389518
TI  - PAHs, PCBs, PBDEs and Pesticides in Cold-Pressed Vegetable Oils.
AB  - The aim of this study was to investigate levels of polychlorinated biphenyls
      (marker and dioxin-like congeners), polycyclic aromatic hydrocarbons (EPA 15 +
      1), polybrominated diphenyl ethers (14 predominant congeners) and pesticides (74
      compounds) in various cold-pressed vegetable oils. Poppy seed oil, rapeseed oil,
      sesame seed oil, pumpkinseed oil, hempseed oil, linaire oil, borage oil and
      evening star oil were investigated. Results of this study revealed that
      concentrations of PCBs, PBDEs and PAHs were low in majority of the investigated
      samples. However, high concentrations of organophosphorus insecticides were
      found. Chlorpyrifos methyl and pirimiphos methyl were the pesticide residues most
      commonly found in the studied oils. Concentration of 15 + 1 EPA PAHs was within
      the 17.85-37.16 MUg kg(-1) range, concentration of (marker) PCBs varied from 127
      to 24,882 pg g(-1), dioxin-like TEQ values were below 0.1 pg TEQ g(-1).
      Concentration of PBDEs was below LOQ in most cases.

PMID- 22389519
TI  - Dip listening and the cocktail party problem in grey treefrogs: Signal
      recognition in temporally fluctuating noise.
AB  - Dip listening refers to our ability to catch brief "acoustic glimpses" of speech
      and other sounds when fluctuating background noise levels momentarily decrease.
      Exploiting dips in natural fluctuations of noise contributes to our ability to
      overcome the "cocktail party problem" of understanding speech in multi-talker
      social environments. We presently know little about how nonhuman animals solve
      analogous communication problems. Here, we asked whether female grey treefrogs
      (Hyla chrysoscelis) might benefit from dip listening in selecting a mate in the
      noisy social setting of a breeding chorus. Consistent with a dip listening
      hypothesis, subjects recognized conspecific calls at lower thresholds when the
      dips in a chorus-like noise masker were long enough to allow glimpses of nine or
      more consecutive pulses. No benefits of dip listening were observed when dips
      were shorter and included five or fewer pulses. Recognition thresholds were
      higher when the noise fluctuated at a rate similar to the pulse rate of the call.
      In a second experiment, advertisement calls comprising six to nine pulses were
      necessary to elicit responses under quiet conditions. Together, these results
      suggest that in frogs, the benefits of dip listening are constrained by neural
      mechanisms underlying temporal pattern recognition. These constraints have
      important implications for the evolution of male signalling strategies in noisy
      social environments.

PMID- 22389520
TI  - Social Support and the Perception of Geographical Slant.
AB  - The visual perception of geographical slant is influenced by physiological
      resources, such as physical fitness, age, and being physically refreshed. In two
      studies we tested whether a psychosocial resource, social support, can also
      affect the visual perception of slants. Participants accompanied by a friend
      estimated a hill to be less steep when compared to participants who were alone
      (Study 1). Similarly, participants who thought of a supportive friend during an
      imagery task saw a hill as less steep than participants who either thought of a
      neutral person or a disliked person (Study 2). In both studies, the effects of
      social relationships on visual perception appear to be mediated by relationship
      quality (i.e., relationship duration, interpersonal closeness, warmth). Artifacts
      such as mood, social desirability, and social facilitation did not account for
      these effects. This research demonstrates that an interpersonal phenomenon,
      social support, can influence visual perception.

PMID- 22389521
TI  - Strangers in sync: Achieving embodied rapport through shared movements.
AB  - This paper examines the emergence of behavioral synchrony among strangers in the
      context of self-disclosure, and their path in predicting interaction quality.
      Specifically, we hypothesize that behavioral synchrony mediates the direct effect
      of self-disclosure on the development of embodied rapport. Same-sex stranger
      pairs (n=94) were randomly assigned to a videorecorded self-disclosure or control
      condition, and afterward each member rated their social interaction. Following
      the procedure used by Bernieri, Reznick, & Rosenthal (1988), two trained judges
      independently watched each video record and rated each pair interaction on
      behavioral synchrony. Bootstrapping analyses provide support for the hypothesized
      mediating effect of behavioral synchrony, which emerged as independent of the
      effects of self-other overlap and positive affect. The authors discuss
      implications of behavioral synchrony for relationship formation processes and the
      inevitable entwinement of behavior and judgments in light of embodied cognition.

PMID- 22389522
TI  - On the anatomy of a chain shift.
AB  - Phonological chain shifts have been the focus of many theoretical, developmental,
      and clinical concerns. This paper considers an overlooked property of the problem
      by focusing on the typological properties of the widely attested 's > theta > f'
      chain shift involving the processes of Labialization and Dentalization in early
      phonological development. Findings are reported from a cross-sectional study of
      234 children (ages 3 years; 0 months-7;9) with functional (nonorganic)
      phonological delays. The results reveal some unexpected gaps in the predicted
      interactions of these processes and are brought to bear on the evaluation of
      recent optimality theoretic proposals for the characterization of phonological
      interactions. A developmental modification to the theory is proposed that has the
      desired effect of precluding certain early-stage grammars. The proposal is
      further evaluated against the facts of another widely cited developmental chain
      shift known as the 'puzzle > puddle > pickle' problem (Smith 1973).

PMID- 22389523
TI  - Effects of acute and chronic cocaine administration on titrating-delay matching
      to-sample performance.
AB  - The effects of cocaine were examined under a titrating-delay matching-to-sample
      procedure. In this procedure, the delay between sample stimulus offset and
      comparison stimuli onset adjusts as a function of the subject's performance.
      Specifically, matches increase the delay and mismatches decrease the delay.
      Titrated delay values served as the primary dependent measure. After establishing
      stable performance in pigeons, several behaviorally-effective doses of cocaine
      were administered acutely. Dose-related within-session decreases in titrated
      delay values were observed. Following acute determinations, the dose of cocaine
      that produced the most rapid decline without eliminating performance was
      administered prior to each daily session. Chronic administration resulted in
      performance trending toward control levels. A redetermination of the dose
      response function following chronic exposure revealed reduced potency (i.e.,
      tolerance) under cocaine on titrated delay matching-to-sample performance.
      Supplemental analyses suggest that cocaine may serve as a disruptor of the
      stimulus conditions in which the performance was established.

PMID- 22389524
TI  - Effects of a meaningful, a discriminative, and a meaningless stimulus on
      equivalence class formation.
AB  - Thirty college students attempted to form three 3-node 5-member equivalence
      classes under the simultaneous protocol. After concurrent training of AB, BC, CD,
      and DE relations, all probes used to assess the emergence of symmetrical,
      transitive, and equivalence relations were presented for two test blocks. When
      the A-E stimuli were all abstract shapes, none of 10 participants formed classes.
      When the A, B, D, and E stimuli were abstract shapes and the C stimuli were
      meaningful pictures, 8 of 10 participants formed classes. This high yield may
      reflect the expansion of existing classes that consist of the associates of the
      meaningful stimuli, rather than the formation of the ABCDE classes, per se. When
      the A-E stimuli were abstract shapes and the C stimuli became S(D)s prior to
      class formation, 5 out of 10 participants formed classes. Thus, the
      discriminative functions served by the meaningful stimuli can account for some of
      the enhancement of class formation produced by the inclusion of a meaningful
      stimulus as a class member. A sorting task, which provided a secondary measure of
      class formation, indicated the formation of all three classes when the emergent
      relations probes indicated the same outcome. In contrast, the sorting test
      indicated "partial" class formation when the emergent relations test indicated no
      class formation. Finally, the effects of nodal distance on the relatedness of
      stimuli in the equivalence classes were not influenced by the functions served by
      the C stimuli in the equivalence classes.

PMID- 22389525
TI  - Effects of economy type and nicotine on the essential value of food in rats.
AB  - The exponential demand equation proposed by Hursh and Silberberg (2008) provides
      an estimate of the essential value of a good as a function of price. The model
      predicts that essential value should remain constant across changes in the
      magnitude of a reinforcer, but may change as a function of motivational
      operations. In Experiment 1, rats' demand for food across a sequence of fixed
      ratio schedules was assessed during open and closed economy conditions and across
      one- and two-pellet per reinforcer delivery conditions. The exponential equation
      was fitted to the relation between fixed-ratio size and the logarithm of the
      absolute number of reinforcers. Estimates of the rate of change in elasticity of
      food, the proposed measure of essential value, were compared across conditions.
      Essential value was equivalent across magnitudes during the closed economy, but
      showed a slight decrease across magnitudes during the open economy. Experiment 2
      explored the behavioral mechanisms of nicotine's effects on consumption with the
      results from Experiment 1 serving as a within-subject frame of reference. The
      same subjects were administered nicotine via subcutaneously implanted osmotic
      minipumps at a dose of 3 mg/kg/day and exposed to both the one- and two-pellet
      conditions under a closed economy. Although nicotine produced large decreases in
      demand, essential value was not significantly changed. The data from the present
      experiments provide further evidence for the adequacy of the exponential demand
      equation as a tool for quantifying the rate of change in elasticity of a good and
      for assessing behavioral mechanisms of drug action.

PMID- 22389526
TI  - Immediate postsession feeding reduces operant responding in rats.
AB  - Three experiments investigated the effects of immediate and delayed postsession
      feeding on progressive-ratio and variable-interval schedule performance in rats.
      During Experiments 1 and 2, immediate postsession feeding decreased the
      breakpoint, or largest completed ratio, under progressive-ratio schedules.
      Experiment 3 was conducted to extend the results of the first two experiments to
      responding maintained by variable-interval schedules with different session
      lengths (15 and 60 min). Response rates decreased in all 4 subjects when
      postsession feeding immediately followed a 15-min session and in 3 of 4 subjects
      when postsession feeding immediately followed a 60-min session. The implications
      of this research are twofold: (1) The functional context in which within-session
      reinforcers are embedded extends outside the experimental chamber, and (2)
      supplemental postsession feedings should be sufficiently delayed from the end of
      a session to avoid weakening operant behavior in the experimental sessions.

PMID- 22389527
TI  - Effects of pre-trial response requirements on self-control choices by rats and
      pigeons.
AB  - Parallel experiments with rats and pigeons examined whether the size of a pre
      trial ratio requirement would affect choices in a self-control situation. In
      different conditions, either 1 response or 40 responses were required before each
      trial. In the first half of each experiment, an adjusting-ratio schedule was
      used, in which subjects could choose a fixed-ratio schedule leading to a small
      reinforcer, or an adjusting-ratio schedule leading to a larger reinforcer. The
      size of the adjusting ratio requirement was increased and decreased over trials
      based on the subject's responses, in order to estimate an indifference point-a
      ratio at which the two alternatives were chosen about equally often. The second
      half of each experiment used an adjusting-delay procedure-fixed and adjusting
      delays to the small and large reinforcers were used instead of ratio
      requirements. In some conditions, particularly with the reinforcer delays, the
      rats had consistently longer adjusting delays with the larger pre-trial ratios,
      reflecting a greater tendency to choose the larger, delayed reinforcer when more
      responding was required to reach the choice point. No consistent effects of the
      pre-trial ratio were found for the pigeons in any of the conditions. These
      results may indicate that rats are more sensitive to the long-term reinforcement
      rates of the two alternatives, or they may result from a shallower temporal
      discounting rate for rats than for pigeons, a difference that has been observed
      in previous studies.

PMID- 22389529
TI  - Design, parametrization, and pole placement of stabilizing output feedback
      compensators via injective cogenerator quotient signal modules.
AB  - Control design belongs to the most important and difficult tasks of control
      engineering and has therefore been treated by many prominent researchers and in
      many textbooks, the systems being generally described by their transfer matrices
      or by Rosenbrock equations and more recently also as behaviors. Our approach to
      controller design uses, in addition to the ideas of our predecessors on coprime
      factorizations of transfer matrices and on the parametrization of stabilizing
      compensators, a new mathematical technique which enables simpler design and also
      new theorems in spite of the many outstanding results of the literature: (1) We
      use an injective cogenerator signal module F over the polynomial algebra
      [Formula: see text] (F an infinite field), a saturated multiplicatively closed
      set T of stable polynomials and its quotient ring [Formula: see text] of stable
      rational functions. This enables the simultaneous treatment of continuous and
      discrete systems and of all notions of stability, called T-stability. We
      investigate stabilizing control design by output feedback of input/output (IO)
      behaviors and study the full feedback IO behavior, especially its autonomous part
      and not only its transfer matrix. (2) The new technique is characterized by the
      permanent application of the injective cogenerator quotient signal module
      [Formula: see text] and of quotient behaviors [Formula: see text] of [Formula:
      see text]-behaviors B. (3) For the control tasks of tracking, disturbance
      rejection, model matching, and decoupling and not necessarily proper plants we
      derive necessary and sufficient conditions for the existence of proper
      stabilizing compensators with proper and stable closed loop behaviors,
      parametrize all such compensators as IO behaviors and not only their transfer
      matrices and give new algorithms for their construction. Moreover we solve the
      problem of pole placement or spectral assignability for the complete feedback
      behavior. The properness of the full feedback behavior ensures the absence of
      impulsive solutions in the continuous case, and that of the compensator enables
      its realization by Kalman state space equations or elementary building blocks. We
      note that every behavior admits an IO decomposition with proper transfer matrix,
      but that most of these decompositions do not have this property, and therefore we
      do not assume the properness of the plant. (4) The new technique can also be
      applied to more general control interconnections according to Willems, in
      particular to two-parameter feedback compensators and to the recent tracking
      framework of Fiaz/Takaba/Trentelman. In contrast to these authors, however, we
      pay special attention to the properness of all constructed transfer matrices
      which requires more subtle algorithms.

PMID- 22389528
TI  - Relational learning in a context of transposition: a review.
AB  - In a typical transposition task, an animal is presented with a single pair of
      stimuli (for example, S3+ S4-, where plus and minus denote reward and nonreward
      and digits denote stimulus location on a sensory dimension such as size).
      Subsequently, an animal is presented with a testing pair that contains a
      previously reinforced or nonreinforced stimulus and a novel stimulus (for
      example, S2-S3 and S4-S5). Does the choice of a novel S2 instead of previously
      reinforced S3 in a testing pair S2-S3 indicate that the animal has learned a
      relation (i.e., "select smaller")? This review of empirical evidence and
      theoretical accounts shows that an organism's behavior in a transposition task is
      undoubtedly influenced by prior reinforcement history of the training stimuli
      (Spence, 1937). However, it is also affected by two other factors that are
      relational in nature-a similarity of two testing stimuli to each other and an
      overall similarity of the testing pair as a whole to the training pair as a
      whole. The influence of the two latter factors is especially evident in studies
      that use multiple pairs of training stimuli and a wide range of testing pairs
      comprising nonadjacent stimuli (Lazareva, Miner, Young, & Wasserman, 2008;
      Lazareva, Wasserman, & Young, 2005). In sum, the evidence suggests that both
      prior reinforcement history and relational information affect an animal's
      behavior in a typical transposition task.

PMID- 22389530
TI  - On the Teaching of Science, Technology and International Affairs.
AB  - Despite the ubiquity and critical importance of science and technology in
      international affairs, their role receives insufficient attention in traditional
      international relations curricula. There is little literature on how the
      relations between science, technology, economics, politics, law and culture
      should be taught in an international context. Since it is impossible even for
      scientists to master all the branches of natural science and engineering that
      affect public policy, the learning goals of students whose primary training is in
      the social sciences should be to get some grounding in the natural sciences or
      engineering, to master basic policy skills, to understand the basic concepts that
      link science and technology to their broader context, and to gain a respect for
      the scientific and technological dimensions of the broader issues they are
      addressing. They also need to cultivate a fearless determination to master what
      they need to know in order to address policy issues, an open-minded but skeptical
      attitude towards the views of dueling experts, regardless of whether they agree
      with their politics, and (for American students) a world-view that goes beyond a
      strictly U.S. perspective on international events. The Georgetown University
      program in Science, Technology and International Affairs (STIA) is a unique,
      multi-disciplinary undergraduate liberal arts program that embodies this approach
      and could be an example that other institutions of higher learning might adapt to
      their own requirements.

PMID- 22389531
TI  - COMPARISON OF PARTICLE-TRACKING FEATURES IN GEANT4 AND MCNPX CODES FOR
      APPLICATIONS IN MAPPING OF PROTON RANGE UNCERTAINTY.
AB  - The accuracy of proton therapy is partially limited by uncertainties that result
      from changing pathological conditions in the patient such as tumor motion and
      shrinkage. These uncertainties can be minimized with the help of a time-resolved
      range telescope. Monte Carlo methods can help improve the performance of range
      telescopes by tracking proton interactions on a particle-by-particle basis thus
      broadening our understanding on the behavior of protons within the patient and
      the detector. This paper compared the proton multiple coulomb scattering
      algorithms in the Monte Carlo codes MCNPX and Geant4 to well-established
      scattering theories. We focus only on beam energies associated with proton
      imaging. Despite slight discrepancies between scattering algorithms, both codes
      appear to be capable of providing useful particle-tracking information for
      applications such as the proton range telescope.

PMID- 22389532
TI  - The financial crisis and the well-being of Americans.
AB  - The Great Recession was associated with large changes in income, wealth, and
      unemployment, changes that affected many lives. Since January 2008, the Gallup
      Organization has been collecting daily data on 1,000 Americans each day, with a
      range of self-reported well-being (SWB) questions. I use these data to examine
      how the recession affected the emotional and evaluative lives of the population,
      as well as of subgroups within it. In the fall of 2008, around the time of the
      collapse of Lehman Brothers, and lasting into the spring of 2009, at the bottom
      of the stock market, Americans reported sharp declines in their life evaluation,
      sharp increases in worry and stress, and declines in positive affect. By the end
      of 2010, in spite of continuing high unemployment, these measures had largely
      recovered, though worry remained higher and life evaluation lower than in January
      2008. The SWB measures do a much better job of monitoring short-run levels of
      anxiety as the crisis unfolded than they do of reflecting the evolution of the
      economy over a year or two. Even large macroeconomic shocks to income and
      unemployment can be expected to produce only small and hard to detect effects on
      SWB measures. SWB, particularly evaluation of life as a whole, is sensitive to
      question order effects. Asking political questions before the life evaluation
      question reduces reported life evaluation by an amount that dwarfs the effects of
      even the worst of the crisis; these order effects persist deep into the
      interview, and condition the reporting of hedonic experience and of satisfaction
      with standard of living. Methods for controlling these effects need to be
      developed and tested if national measures are to be comparable over space and
      time.

PMID- 22389533
TI  - The Power of the Pill for the Next Generation: Oral Contraception's Effects on
      Fertility, Abortion, and Maternal & Child Characteristics.
AB  - This paper considers how oral contraception's diffusion to young unmarried women
      affected the number and parental characteristics of children born to these women.
      In the short-term, pill access caused declines in fertility and increases in both
      the share of children born with low birthweight and the share born to poor
      households. In the long-term, access led to negligible changes in fertility while
      increasing the share of children with college-educated mothers and decreasing the
      share with divorced mothers. The short-term effects appear to be driven by
      upwardly-mobile women opting out of early childbearing while the long-term
      effects appear to be driven by a retiming of births to later ages. These effects
      differ from those of abortion legalization, although we find suggestive evidence
      that pill diffusion lowered abortions. Our results suggest that abortion and the
      pill are on average used for different purposes by different women, but on the
      margin some women substitute from abortion towards the pill when both are
      available. JELNo. I0, J13, N12.

PMID- 22389534
TI  - Fitting in: the roles of social acceptance and discrimination in shaping the
      daily psychological well-being of Latino youth.
AB  - OBJECTIVES: We examine how acculturation experiences such as discrimination and
      social acceptance influence the daily psychological well-being of Latino youth
      living in newly emerging and historical receiving immigrant communities. METHODS:
      We use data on 557 Latino youth enrolled in high school in Los Angeles or in
      rural or urban North Carolina. RESULTS: Compared to Latino youth in Los Angeles,
      Latino youth in urban and rural North Carolina experienced higher levels of daily
      happiness, but also experienced higher levels of daily depressive and anxiety
      symptoms. Differences in nativity status partially explained location differences
      in youths' daily psychological well-being. Discrimination and daily negative
      ethnic treatment worsened, whereas social acceptance combined with daily positive
      ethnic treatment and ethnic and family identification improved, daily
      psychological well-being. CONCLUSIONS: Our analysis contributes to understanding
      the acculturation experiences of immigrant youth and the roles of social context
      in shaping adolescent mental health.

PMID- 22389535
TI  - Interactive and Single Effects of Ectomycorrhiza Formation and Bacillus cereus on
      Metallothionein MT1 Expression and Phytoextraction of Cd and Zn by Willows.
AB  - Single and joint ectomycorrhizal (+ Hebeloma mesophaeum) and bacterial (+
      Bacillus cereus) inoculations of willows (Salix viminalis) were investigated for
      their potential and mode of action in the promotion of cadmium (Cd) and zinc (Zn)
      phytoextraction. Dual fungal and bacterial inoculations promoted the biomass
      production of willows in contaminated soil. Single inoculations either had no
      effect on the plant growth or inhibited it. All inoculated willows showed
      increased concentrations of nutritional elements (N, P, K and Zn) and decreased
      concentrations of Cd in the shoots. The lowest biomass production and
      concentration of Cd in the willows (+ B. cereus) were combined with the strongest
      expression of metallothioneins. It seems that biotic stress from bacterial
      invasion increased the synthesis of these stress proteins, which responded in
      decreased Cd concentrations. Contents of Cd and Zn in the stems of willows were
      combination-specific, but were always increased in dual inoculated plants. In
      conclusion, single inoculations with former mycorrhiza-associated B. cereus
      strains decreased the phytoextraction efficiency of willows by causing biotic
      stress. However, their joint inoculation with an ectomycorrhizal fungus is a very
      promising method for promoting the phytoextraction of Cd and Zn through combined
      physiological effects on the plant.

PMID- 22389536
TI  - Nanoscale Metallic Iron for Environmental Remediation: Prospects and Limitations.
AB  - The amendment of the subsurface with nanoscale metallic iron particles (nano
      Fe(0)) has been discussed in the literature as an efficient in situ technology
      for groundwater remediation. However, the introduction of this technology was
      controversial and its efficiency has never been univocally established. This
      unsatisfying situation has motivated this communication whose objective was a
      comprehensive discussion of the intrinsic reactivity of nano-Fe(0) based on the
      contemporary knowledge on the mechanism of contaminant removal by Fe(0) and a
      mathematical model. It is showed that due to limitations of the mass transfer of
      nano-Fe(0) to contaminants, available concepts cannot explain the success of nano
      Fe(0) injection for in situ groundwater remediation. It is recommended to test
      the possibility of introducing nano-Fe(0) to initiate the formation of roll
      fronts which propagation would induce the reductive transformation of both
      dissolved and adsorbed contaminants. Within a roll-front, Fe(II) from nano-Fe(0)
      is the reducing agent for contaminants. Fe(II) is recycled by biotic or abiotic
      Fe(III) reduction. While the roll-front concept could explain the success of
      already implemented reaction zones, more research is needed for a science-based
      recommendation of nano-Fe(0) for subsurface treatment by roll-fronts.

PMID- 22389537
TI  - Effect of Divalent Ions on Electroosmotic Flow in Microchannels.
AB  - The electroosmotic flow (EOF) rate in fused silica microchannels is
      experimentally found to decrease when trace quantities of salts containing the
      divalent cations Ca(2+) and Mg(2+) are added to a constant ionic strength
      background electrolytic solution (BGE) flowing in a channel having negatively
      charged walls. Moreover, the observed effect is quantitatively different for the
      two ions Ca(2+) and Mg(2+). Since electrostatic interactions are identical for
      ions of the same valence modeled as point charges, a description of the electric
      double layer (EDL) based on the Poisson-Boltzmann equation alone cannot account
      for these experimental observations. New experimental observations on
      electroosmotic flow in presence of Ca(2+) and Mg(2+) are reported in this work. A
      site binding model that accounts for the chemical interactions of the BGE ions
      with the silica surface is developed. The model predictions are in good agreement
      with the experimental observations on divalent cations as well as data from the
      literature on how properties such as pH and ionic strength affect electroosmotic
      flow rates for a BGE with monovalent cations.

PMID- 22389538
TI  - CROSS-SIBLING EFFECTS IN PARENT-ADULT CHILD EXCHANGES OF SOCIOEMOTIONAL SUPPORT.
AB  - We use National Survey of Families and Households first wave data and innovative
      modeling to examine how one parent-adult child pair may affect other pairs. Three
      conceptual models guide our analyses of parents' giving and receiving of
      socioemotional support, representing enhancement, compensation, and independence.
      Giving support to one child is related to more giving to others (enhancement),
      but receiving support from one child is related to less receipt from others
      (compensation). Cross-sibling interactions do not reveal significant effects of
      distance of one child on exchanges with others, nor of gender or stepchild status
      of adult children. Cross-sibling interactions differ by race, suggesting
      enhancement in receiving support among Blacks and enhancement in giving support
      among non-Blacks. These analyses demonstrate the value of examining how parent
      adult child ties are influenced by each other and by their family context.

PMID- 22389539
TI  - Male Mating Tactics in Captive Rhesus Macaques (Macaca mulatta): The Influence of
      Dominance, Markets, and Relationship Quality.
AB  - Male mating success in a multimale-multifemale group can depend on several
      variables: body condition, dominance, coalitions, "friendship," or an exchange of
      services for mating access. Exchange patterns may also be determined by market
      effects or social relationships. We studied the mating tactics of males in a
      captive, multimale-multifemale group of rhesus macaques and the resulting
      patterns of mating and paternity to determine the influence of dominance rank,
      mating markets, and relationship quality on their mating tactics. Male rank was
      positively related to the total number of copulations and the number of mating
      partners, but did not explain male mating distribution completely. Moreover, male
      fertilization success was not related to male rank. Males did not exchange
      grooming for mating access on the same day and neither the supply nor the rank
      (as a proxy for quality) of receptive females affected the amount of male
      grooming, suggesting that market effects did not explain male mating access.
      However, there was a positive correlation between long-term grooming patterns of
      both males and females and mating access, indicating that social relationships
      were important for male mating access. Paternity data revealed that these social
      relationships were also important for male reproductive success. We conclude that
      both male rank and male-female "friendship" determined male mating access in
      these rhesus macaques, but that "friendship" was more important in determining
      paternity, emphasizing the importance of intersex social bonds in male mating
      success in multimale primate societies. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s10764-011-9552-5) contains
      supplementary material, which is available to authorized users.

PMID- 22389540
TI  - ?
AB  - We use projected Delaunay tetrahedra and a maximum independent set approach to
      compute large subsets of convex quadrangulations on a given set of points in the
      plane. The new method improves over the popular pairing method based on
      triangulating the point set.

PMID- 22389541
TI  - Lamina Cribrosa Thickening in Early Glaucoma Predicted by a Microstructure
      Motivated Growth and Remodeling Approach.
AB  - Glaucoma is among the leading causes of blindness worldwide. The ocular disease
      is characterized by irreversible damage of the retinal ganglion cell axons at the
      level of the lamina cribrosa (LC). The LC is a porous, connective tissue
      structure whose function is believed to provide mechanical support to the axons
      as they exit the eye on their path from the retina to the brain. Early
      experimental glaucoma studies have shown that the LC remodels into a thicker,
      more posterior structure which incorporates more connective tissue after
      intraocular pressure (IOP) elevation. The process by which this occurs is
      unknown. Here we present a microstructure motivated growth and remodeling (G&R)
      formulation to explore a potential mechanism of these structural changes. We
      hypothesize that the mechanical strain experienced by the collagen fibrils in the
      LC stimulates the G&R response at the micro-scale. The proposed G&R algorithm
      controls collagen fibril synthesis/degradation and adapts the residual strains
      between collagen fibrils and the surrounding tissue to achieve biomechanical
      homeostasis. The G&R algorithm was applied to a generic finite element model of
      the human eye subjected to normal and elevated IOP. The G&R simulation
      underscores the biomechanical need for a LC at normal IOP. The numerical results
      suggest that IOP elevation leads to LC thickening due to an increase in collagen
      fibril mass, which is in good agreement with experimental observations in early
      glaucoma monkey eyes. This is the first study to demonstrate that a
      biomechanically-driven G&R mechanism can lead to the LC thickening observed in
      early experimental glaucoma.

PMID- 22389542
TI  - Alkali halide clusters produced by fast ion impact.
AB  - The most abundant geometries and relative stabilities of alkali halide clusters
      with a (XY)(n) (o) configuration (e.g., LiF, NaCl, KBr) are described. Five main
      series were obtained: linear, cyclic, cubic, arc strips and nanotubes. The
      stability analysis shows that higher members are likely to be formed from the
      lower member of the same series and/or from two building blocks (n = 1, 2). The
      energy analysis (D-plot) indicates that the most compact ones (e.g., cubic and
      nanotubes) present higher stability when compared to the linear, cyclic and arc
      strip structures; moreover, relative stability between the cubic and nanotube
      series varies with the cluster size.

PMID- 22389543
TI  - Girls in Foster Care: Risk and Promotive Factors for School Adjustment Across the
      Transition to Middle School.
AB  - Girls in foster care may face difficulties across the transition to middle
      school. Latent growth curve modeling was employed to examine trajectories and
      predictors of academic competence and aggression from and against peers for 75
      girls in foster care from the end of elementary school to the 2(nd) year of
      middle school. Across the transition to middle school, academic competence
      increased. Poor self-regulation was associated with decreased academic
      competence, and higher caregiver support was associated with increased academic
      competence. Frequency of aggression from peers decreased across the transition,
      with perceived school competence predicting smaller decreases. Aggression against
      peers dropped initially and then increased to pretransition levels by the end of
      the 2(nd) year of middle school. Lower caregiver support was associated with
      higher rates of aggression against peers at the end of the 1(st) year of middle
      school. The results are discussed in terms of implications for interventions for
      girls in foster care.

PMID- 22389544
TI  - Facilitating Mental Health Service Use for Caregivers: Referral Strategies among
      Child Welfare Caseworkers.
AB  - Unmet needs for mental health care are common among caregivers involved in the
      child welfare system. Although child welfare caseworkers are well positioned to
      identify service needs and refer caregivers to treatment, little is known about
      the types of referral strategies used in practice, or their effectiveness for
      promoting mental health service use. The current study examined child welfare
      caseworkers' use of different referral strategies and the extent to which these
      strategies are associated with caregivers' receipt of mental health services
      within a national sample of child welfare cases. Analyses of the second cohort of
      families from the National Survey of Child and Adolescent Well-Being suggest that
      child welfare workers more often use informational strategies for referring
      caregivers, including suggesting treatment or providing information about
      treatment options. However, social referral strategies such as providing
      caregivers with direct assistance in completing applications and making and
      attending appointments were associated with a greater likelihood of caregivers
      receiving mental health services. Findings support evidence from other service
      contexts that service use is facilitated by caseworkers' direct support for
      arranging services. Implications for research and for child welfare managers and
      administrators are discussed.

PMID- 22389545
TI  - Assessing negative cognitive style: Development and validation of a Short-Form
      version of the Cognitive Style Questionnaire.
AB  - The Cognitive Style Questionnaire (CSQ) is a frequently employed measure of
      negative cognitive style, associated with vulnerability to anxiety and
      depression. However, the CSQ's length can limit its utility in research. We
      describe the development of a Short-Form version of the CSQ. After evaluation and
      modification of two pilot versions, the 8-item CSQ Short Form (CSQ-SF) was
      administered to a convenience sample of adults (N = 278). The CSQ-SF was found to
      have satisfactory internal reliability and test-retest reliability. It also
      exhibited construct validity by demonstrating predicted correlations with
      measures of depression and anxiety. Results suggest that the CSQ-SF is suitable
      for administration via the Internet.

PMID- 22389546
TI  - Accounting for Movement between Childcare Classrooms: Does it Change Teacher
      Effects Interpretations?
AB  - Child care studies that have examined links between teachers' qualifications and
      children's outcomes often ignore teachers' and children's transitions between
      classrooms at a center throughout the day and only take into account head teacher
      qualifications. The objective of this investigation was to examine these
      traditional assumptions and to compare inferences made from these traditional
      models to methods accounting for transitions between classrooms and multiple
      teachers in a classroom. The study examined the receptive language, letter-word
      identification, and passage comprehension skills of 307 children enrolled in 49
      community-based childcare centers serving primarily low-income families in
      Colorado. Results suggest that nearly one-third of children and over 80% of
      teachers moved daily between classrooms. Findings also reveal that failure to
      account for daily transitions between classrooms can affect interpretations of
      the relationship between teacher qualifications and child outcomes, with the
      model accounting for movement providing significant improvements in model fit and
      inference.

PMID- 22389547
TI  - Better With Age: Social Relationships Across Adulthood.
AB  - Older adults typically report higher levels of satisfaction with their social
      relationships than younger adults. The present paper integrates current
      developmental research to explain why social relationships are generally more
      positive with age. We discuss actions by older adults that contribute to more
      positive social experiences. We also include social role changes that may provide
      advantages for older adults when navigating their relationships. Next, we turn to
      interactional processes between older adults with their social partners. We
      review literature indicating that: (a) older adults engage in strategies that
      optimize positive social experiences and minimize negative ones by avoiding
      conflicts, and (b) social partners often reciprocate by treating older adults
      more positively and with greater forgiveness than they do younger adults.

PMID- 22389548
TI  - Agent-based modeling of the effects of social norms on enrollment in payments for
      ecosystem services.
AB  - Conservation investments are increasingly being implemented through payments for
      ecosystem services (PES) for the protection and restoration of ecosystem services
      around the world. Previous studies suggested that social norms have substantial
      impacts on environmental behaviors of humans, including enrollment of PES
      programs. However, it is still not well understood how social norms are affected
      by the design of PES programs and how the evolution of social norms may affect
      the efficiency of conservation investments. In this paper, we developed an agent
      based simulation model to demonstrate the evolution and impacts of social norms
      on the enrollment of agricultural land in a PES program. We applied the model to
      land plots that have been enrolled in China's Grain-to-Green Program (GTGP) to
      examine reenrollment in an alternative payment program when the current payments
      ceased. The study was conducted in Wolong Nature Reserve where several thousand
      plant and animal species, including giant pandas, may benefit from the
      reenrollment. We found that over 15% more GTGP land can be reenrolled at the same
      payment if social norms were leveraged by allowing more than ten rounds of
      interactions among landholders regarding their reenrollment decisions. With only
      three rounds of interactions, an additional 7.5% GTGP land was reenrolled at the
      same payment due to the effects of social norms. In addition, the effects of
      social norms were largest at intermediate payments and were smaller at much
      higher or much smaller payments. Even in circumstances where frequent
      interactions among landholders about their enrollment decisions are not feasible,
      policy arrangements that divide households into multiple waves for sequential
      enrollment can enroll over 11% more land at a given payment level. The approach
      presented in this paper can be used to improve the efficiency of existing PES
      programs and many other conservation investments worldwide.

PMID- 22389549
TI  - A curvilinear effect of height on reproductive success in human males.
AB  - Human male height is associated with mate choice and intra-sexual competition,
      and therefore potentially with reproductive success. A literature review (n = 18)
      on the relationship between male height and reproductive success revealed a
      variety of relationships ranging from negative to curvilinear to positive. Some
      of the variation in results may stem from methodological issues, such as low
      power, including men in the sample who have not yet ended their reproductive
      career, or not controlling for important potential confounders (e.g. education
      and income). We investigated the associations between height, education, income
      and the number of surviving children in a large longitudinal sample of men (n =
      3,578; Wisconsin Longitudinal Study), who likely had ended their reproductive
      careers (e.g. > 64 years). There was a curvilinear association between height and
      number of children, with men of average height attaining the highest reproductive
      success. This curvilinear relationship remained after controlling for education
      and income, which were associated with both reproductive success and height.
      Average height men also married at a younger age than shorter and taller men, and
      the effect of height diminished after controlling for this association. Thus,
      average height men partly achieved higher reproductive success by marrying at a
      younger age. On the basis of our literature review and our data, we conclude that
      men of average height most likely have higher reproductive success than either
      short or tall men. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s00265-011-1283-2) contains supplementary material, which is
      available to authorized users.

PMID- 22389550
TI  - ?
AB  - The existence of weak solutions to the continuous coagulation equation with
      multiple fragmentation is shown for a class of unbounded coagulation and
      fragmentation kernels, the fragmentation kernel having possibly a singularity at
      the origin. This result extends previous ones where either boundedness of the
      coagulation kernel or no singularity at the origin for the fragmentation kernel
      was assumed.

PMID- 22389551
TI  - Predictors and Outcomes of Early vs. Later English Language Proficiency Among
      English Language Learners.
AB  - The development of English language learners (ELLs) was explored from
      kindergarten through eighth grade within a nationally representative sample of
      first-time kindergartners (N = 19,890). Growth curve analyses indicated that,
      compared to native English speakers, ELLs were rated by teachers more favorably
      on approaches to learning, self control, and externalizing behaviors in
      kindergarten and generally continued to grow in a positive direction on these
      social/behavioral outcomes at a steeper rate compared to their native English
      speaking peers, holding other factors constant. Differences in reading and math
      achievement between ELLs and native English speakers varied based on the grade at
      which English proficiency is attained. Specifically, ELLs who were proficient in
      English by kindergarten entry kept pace with native English speakers in both
      reading and math initially and over time; ELLs who were proficient by first grade
      had modest gaps in reading and math achievement compared to native English
      speakers that closed narrowly or persisted over time; and ELLs who were not
      proficient by first grade had the largest initial gaps in reading and math
      achievement compared to native speakers but the gap narrowed over time in reading
      and grew over time in math. Among those whose home language is not English,
      acquiring English proficiency by kindergarten entry was associated with better
      cognitive and behavioral outcomes through eighth grade compared to taking longer
      to achieve proficiency. Multinomial regression analyses indicated that child,
      family, and school characteristics predict achieving English proficiency by
      kindergarten entry compared to achieving proficiency later. Results are discussed
      in terms of policies and practices that can support ELL children's growth and
      development.

PMID- 22389552
TI  - Comparison of Parent and Child Reports on Child Maltreatment in a Representative
      Household Sample in Hong Kong.
AB  - This study investigated and compared the rates of child maltreatment as reported
      by parents and children. Self-reports of 1,093 children aged 12 to 18, which were
      matched with both parents' records, were compared and analyzed in the study. The
      levels of agreement between parent and child reporting of various kinds of
      parental child maltreatment were low to moderate. Factors affecting the
      disagreement in reports were also investigated. Social desirability and violence
      approval were the common predictors of disagreement in father-child and mother
      child reports, respectively. The low agreement between parent-child reports found
      in the present study highlights the need for the inclusion of both parent and
      child reports on maltreatment in future clinical screening and intervention
      programs.

PMID- 22389553
TI  - Risk of Revictimization of Intimate Partner Violence: The Role of Attachment,
      Anger and Violent Behavior of the Victim.
AB  - Victims of intimate partner violence (IPV) are known to be at high risk for
      revictimization. Yet, to date, the mechanisms explaining the link between
      victimization and revictimization of IPV have not been extensively studied. In
      the present prospective study involving 74 female help-seeking victims of IPV, we
      investigated victim-related psychological mechanisms that may underlie this link.
      With this study, we aim to contribute to the development of theory addressing
      these psychological mechanisms and their role in explaining risk for IPV
      revictimization. Hypotheses regarding possibly relevant psychological mechanisms
      were derived from two conflicting approaches to IPV: the gender perspective, and
      the mutual IPV perspective. Results lend further support to the mutual IPV
      perspective, since our final prediction model indicates that victim-perpetrated
      IPV is an important risk factor for physical and psychological IPV
      revictimization. An avoidant attachment style shows to be a strong predictor as
      well, in particular for victims with high and average anger levels. Findings
      provide clear indications for risk assessment and treatment of IPV victims, and
      moreover offer opportunities to empower these victims in order to prevent future
      violence.

PMID- 22389554
TI  - Evaluation of the Food and Nutrient Database for Dietary Studies for use with a
      mobile telephone food record.
AB  - The development of a mobile telephone food record (mpFR) in which image analysis
      and volume estimation data can be indexed with the Food and Nutrient Database for
      Dietary Studies (FNDDS) has the potential to improve the accuracy of dietary
      assessment. To validate the mpFR for use with adolescents, a convenience sample
      of adolescents, aged 11-18 years, was recruited to eat all meals and snacks in a
      controlled feeding environment over a 24-hour period. Each food item matched a
      food code in the FNDDS 3.0. The objective of this analysis was to compare the
      measured energy and protein content of foods to the published values in the
      FNDDS. Duplicate plates of all meals and snacks were prepared, and samples of 20
      foods were individually weighed, homogenized, freeze dried, and analyzed for
      energy with a bomb calorimeter and for protein with a Dumas nitrogen analyzer.
      Eleven of the twenty food items had energy values in the FNDDS within +/-10% of
      the measured energy value. The measured energy and protein values from all foods
      correlated significantly with the energy (r=0.981, P<0.01) and protein (r= 0.911,
      P<0.01) values in the FNDDS. These results support the use of the FNDDS with the
      mpFR.

PMID- 22389555
TI  - The monobloc hydrogel breast implant, experiences and ideas.
AB  - This study is focused on the properties of the monobloc hydrogel (MH) breast
      implant, which has been around for more than 30 years, and to see how it behaves
      with regard to health complaints as sometimes seen in some patients who had
      received silicone gel (SG) breast implants. Patients responded to a questionnaire
      examining their experience with breast implants. Three groups were included.
      First, the control group (n = 34) of women without breast implants. Second, a C
      group of women (n = 42) who began and remained on the MH implant. Third, the B
      group of women who had their silicone gel implant replaced by the MH implant. In
      the B1 subgroup (n = 22), a capsulectomy was also performed. In the B2 subgroup
      (n = 13), the replacement was carried out without a capsulectomy. The C group
      behaved very much like the control group. The women of the B group experienced an
      improvement of their complaints and the improvement was even better after a
      capsulectomy. The only difference between the MH and SG implants is the content
      of the implant. The satisfaction of women with MH implants is generally high and
      not or hardly associated with health complaints. In women with SG implants and
      health complaints, these complaints can be relieved by replacement of the
      implants by MH implants.

PMID- 22389556
TI  - A case of complication after a degloving operation of melanoma of the penis
      repairing urethrocutaneous fistula with a pedicled gracilis flap.

PMID- 22389557
TI  - Instruments and consumables.

PMID- 22389559
TI  - Useful resources: instruments and consumables.

PMID- 22389558
TI  - Instruments for cataract surgery: results from our survey.

PMID- 22389560
TI  - Instrument care: everyone's responsibility.

PMID- 22389561
TI  - Managing your eye unit's supplies.

PMID- 22389562
TI  - A simple paper-based system for stock management.

PMID- 22389563
TI  - Care of ophthalmic surgical instruments.

PMID- 22389564
TI  - Purchasing instruments and consumables.

PMID- 22389565
TI  - Donations of consumables and surgical instruments: how to ensure you really
      benefit.

PMID- 22389566
TI  - Optical products for refractive error and low vision.

PMID- 22389567
TI  - Sharpening and tightening surgical scissors.

PMID- 22389568
TI  - Schirmer's test.

PMID- 22389570
TI  - CPD: Test yourself.

PMID- 22389569
TI  - New DVD supports trachoma surgery training.

PMID- 22389572
TI  - The biopolitics of needle exchange in the United States.
AB  - Needle exchange began in the United States as a fragmented and illegal practice
      initiated by actors at the grassroots level; since the late 1980s, needle
      exchange has achieved increasing yet variable levels of institutional support
      across the country, receiving official sanction and funding from state and
      municipal governments. In turn, the practice(s) and discourse(s) of needle
      exchange have shifted significantly in many locales, becoming the purview of
      professional administration that advocates needle exchange as a necessary public
      health measure. This article is interested in the ways in which needle exchange
      has become implicated in and appropriated by networks of power seeking to
      discipline and regulate injection drug use. Drawing theoretically on Michel
      Foucault's writings concerning biopower and governmentality, it will examine the
      proliferation of discourses, knowledges, and rules surrounding needle exchange in
      the United States. At the same time, this article will avoid a characterization
      of needle exchange that envisions the unilateral control of drug users by
      governmental power, illuminating instead both its negative and productive effects
      for drug users. Namely, it will explore how needle exchange creates both subjects
      of interest and subjects of resistance among drug users - that is to say, the
      governmentalization of needle exchange and its 'clients'.

PMID- 22389573
TI  - MPI Cell Tracking: What Can We Learn from MRI?
AB  - Magnetic resonance imaging (MRI) cell tracking has become an important non
      invasive technique to interrogate the fate of cells upon transplantation. At
      least 6 clinical trials have been published at the end of 2010, all of which have
      shown that real-time monitoring of the injection procedure, initial engraftment,
      and short-term biodistribution of cells is critical to further advance the field
      of cellular therapeutics. In MRI cell tracking, cells are loaded with
      superparamagnetic iron oxide (SPIO) particles that provide an MRI contrast effect
      through microscopic magnetic field disturbances and dephasing of protons.
      Magnetic particle imaging (MPI) has recently emerged as a potential cellular
      imaging technique that promises to have several advantages over MRI, primarily
      linear quantification of cells, a higher sensitivity, and "hot spot" tracer
      identification without confounding background signal. Although probably not fully
      optimized, SPIO particles that are currently used as MRI contrast agent can be
      employed as MPI tracer. Initial studies have shown that cells loaded with SPIO
      particles can give a detectable MPI signal, encouraging further development of
      MPI cell tracking.

PMID- 22389574
TI  - N-Ethylmaleimide Stimulates and Inhibits Ion Transport in Vestibular Dark Cells
      of Gerbil.
AB  - Vestibular dark cell epithelium was isolated from the semicircular canal of
      gerbils to test the proposal that the sulfhydryl alkylating agent N
      ethylmaleimide (NEM) inhibits K(+) secretion by this tissue and does so by
      reacting with a site in or near the apical membrane. Dark cell epithelium was
      mounted in a micro-Ussing chamber for measurements of transepithelial voltage
      (V(t)) and resistance (R(t)) or in a perfused bath on the stage of a microscope
      for measurement of cell height as an index of cell volume. Perfusion of the
      apical or basolateral side with 10(-3) M NEM caused an increase in V(t)
      superimposed upon a slower decrease of V(t), resulting in a triphasic response.
      There were only small changes in R(t). Under this condition, V(t) is proportional
      to short circuit current and to K(+) secretion. Both the stimulatory and the
      inhibitory responses of V(t) were dose-dependent between 10(-6) and 10(-3) M NEM
      and the inhibition was irreversible. The specificity of the reaction of NEM with
      sulfhydryl groups was confirmed by the use of the reducing agent dithiothreitol
      (DTT). Perfusion of 5*10(-4) M DTT on the apical side caused no significant
      changes in V(t) but completely prevented both stimulation and inhibition of V(t)
      by NEM (10(-3) M). The amplitudes of the stimulation and the inhibition of V(t)
      were greater for basolateral than for apical perfusion of NEM. Similarly, the
      response times for each effect were faster from the basolateral side, suggesting
      that the primary sites of action are at or near the basolateral membrane. The
      site of action of NEM was further explored by subjecting the tissue to a membrane
      impermeant sulfhydryl reagent, stilbenedisulfonate maleimide (SDM). Apical
      perfusion of 10(-3) M SDM had no effect on V(t) or R(t), whereas basolateral
      perfusion caused a reversible increase of V(t) (5.2 +/- 0.5 to initially 6.8 +/-
      0.5 mV which relaxed after 60 s to 5.8 +/- 0.5 mV) and to an initial decrease in
      R(t) by 4%. No inhibitory phase was observed. Elevation of basolateral [K(+)]
      from 3.6 to 25 mM is known to increase V(t) and reduce R(t) via direct
      stimulation of basolateral K(+) uptake and indirect stimulation of the apical
      membrane conductance. Basolateral perfusion of 10(-3) M NEM fully inhibited the
      increase of V(t) due to 25 mM K(+). Elevation of basolateral [K(+)] from 3.6 to
      25 mM is known to increase reversibly cell volume. NEM was found to inhibit cell
      swelling in a dose-dependent manner but did not initially affect the rate of
      shrinking after K(+)-induced swelling, pointing to action only on basolateral
      transport pathways. The effects of NEM on K(+)-induced cell swelling were
      completely prevented by 5*10(-4) M DTT, demonstrating that the inhibitory effect
      of NEM was on sulfhydryl groups. In contrast to interpretations of NEM action in
      frog semicircular canal, we have found that NEM appears to stimulate an ion
      transport process in mammalian dark cells at an extracellular site in the
      basolateral membrane and inhibits another ion transport process in the
      basolateral membrane at another site. Inhibition by NEM from the apical side
      occurs most likely by diffusion of the agent to a site at or near the cytosolic
      side of the basolateral membrane.

PMID- 22389575
TI  - Resisting Smoking When a Best Friend Smokes: Do Intrapersonal and Contextual
      Factors Matter?
AB  - This longitudinal study examines individual differences in the tendency to
      initiate (N = 4,612) and escalate (N = 2,837) smoking when adolescents gain a
      best friend who smokes. Potential moderating factors include self-esteem,
      depression, problem behavior, school and family bonds, and household access to
      cigarettes. In addition to acquiring a smoking best friend, initiation was
      predicted by trouble at school, household access, poorer grades and delinquency,
      whereas escalation was predicted by depressive symptoms. There was little
      evidence that the examined individual difference factors moderate the association
      between gaining a smoking best friend and increased adolescent smoking. Results
      point to the challenges of identifying factors that may lead adolescents to be
      more or less susceptible to the influence of pro-smoking friends.

PMID- 22389576
TI  - Neighborhood & Family Effects on Learning Motivation among Urban African American
      Middle School Youth.
AB  - Motivational theorists in psychology have moved away from individual-based
      approaches to socio-cognitive and socio-ecological models to explain student
      engagement and motivation for learning. Such approaches consider, for example,
      the influence of family and neighborhood environments as important constructs in
      youth behavior. In this study, links between neighborhood condition (e.g.
      external appearance of the blocks nearest to the respondents' home), family
      dysfunction, and motivation for learning are investigated. Data were obtained
      from two hundred and sixteen (216) urban African American middle school children
      enrolled in a substance use prevention intervention. Analytic models show
      associations between poor neighborhood condition and both family dysfunction and
      lower learning motivation. Family dysfunction was also found to mediate the
      effect of neighborhood condition on motivated learning. Neighborhood and family
      characteristics are important determinants of urban schoolchildren's motivation
      for learning.

PMID- 22389577
TI  - Money Matters: Cost Effectiveness of Juvenile Drug Court with and without
      Evidence-Based Treatments.
AB  - The 12-month cost effectiveness of juvenile drug court and evidence-based
      treatments within Court were compared with traditional Family Court for 128
      substance abusing/dependent juvenile offenders participating in a four-condition
      randomized trial. Intervention conditions included Family Court with community
      services (FC), Drug Court with community services (DC), Drug Court with
      Multisystemic Therapy (DC/MST), and Drug Court with MST enhanced with a
      contingency management program (DC/MST/CM). Average cost effectiveness ratios for
      substance use and criminal behavior outcomes revealed that economic efficiency in
      achieving outcomes generally improved from FC to DC, with the addition of
      evidence-based treatments improving efficiency in obtaining substance use
      outcomes.

PMID- 22389578
TI  - Rank-Constrained Solutions to Linear Matrix Equations Using PowerFactorization.
AB  - Algorithms to construct/recover low-rank matrices satisfying a set of linear
      equality constraints have important applications in many signal processing
      contexts. Recently, theoretical guarantees for minimum-rank matrix recovery have
      been proven for nuclear norm minimization (NNM), which can be solved using
      standard convex optimization approaches. While nuclear norm minimization is
      effective, it can be computationally demanding. In this work, we explore the use
      of the PowerFactorization (PF) algorithm as a tool for rank-constrained matrix
      recovery. Empirical results indicate that incremented-rank PF is significantly
      more successful than NNM at recovering low-rank matrices, in addition to being
      faster.

PMID- 22389579
TI  - Zen and the Art of Surgery: How to Make Johnny a Surgeon.

PMID- 22389580
TI  - Synthesis and Biocidal Activity of Some Naphthalene-Based Cationic Surfactants.
AB  - In this study, different cationic surfactants were prepared by reacting dodecyl
      bromide with tertiary amines to produce a series of quaternary ammonium salts
      that were converted subsequently to stannous and cobalt cationic complexes via
      complexing them with stannous (II) or cobalt (II) ions. Surface properties such
      as surface- and interfacial-tension, and the emulsifying power of these
      surfactants were investigated. The surface parameters including critical micelle
      concentration, maximum surface excess, minimum surface area, tension lowering
      efficiency and effectiveness were studied. The free energy of micellization and
      adsorption were calculated. Antimicrobial activity was determined via the
      inhibition zone diameter of the prepared compounds, which was measured against
      six strains of a representative group of microorganisms. The antimicrobial
      activity of some of the prepared surfactants against sulfate reducing bacteria
      was determined by the dilution method. FTIR spectra, elemental analysis and a
      H(1) NMR spectrum were examined to confirm compound structure and purity. The
      results obtained indicate that these compounds have good surface properties and
      good biocidal effect on broad spectrum of micro organisms.

PMID- 22389581
TI  - Raltegravir in HIV-1 infection: Safety and Efficacy in Treatment-naive Patients.
AB  - The hunt for a compound which inhibits the HIV-1 integrase had been painstakingly
      difficult. Integrase is essential for viral replication as it mediates the
      integration of the viral DNA genome into the host DNA resulting in the
      establishment of the permanent provirus. Persistent efforts have resulted in the
      discovery of Raltegravir (Isentress, MK-0518), the first integrase inhibitor
      approved by US Food and Drug Administration for the treatment in HIV-1 infected
      patients. Numerous clinical studies with raltegravir have found it to be safe and
      effective in treatment naive as well as treatment experienced patients. Adverse
      events associated with raltegravir based therapy are milder compared to
      previously available regimens. Raltegravir is metabolized primarily via
      glucuronidation mediated by uridine diphosphate glucuronosyltransferase and has a
      favorable pharmacokinetics independent of age, gender, race, food, and drug-drug
      interactions. Within a short period of time of its introduction, raltegravir has
      been included as one of DHHS recommended preferred regimen for the treatment of
      HIV-1 infection in treatment naive patients.

PMID- 22389582
TI  - Survival on the ark: life history trends in captive parrots.
AB  - Members of the order Psittaciformes (parrots and cockatoos) are among the most
      long-lived and endangered avian species. Comprehensive data on lifespan and
      breeding are critical to setting conservation priorities, parameterizing
      population viability models, and managing captive and wild populations. To meet
      these needs, we analyzed 83, 212 life history records of captive birds from the
      International Species Information System and calculated lifespan and breeding
      parameters for 260 species of parrots (71% of extant species). Species varied
      widely in lifespan, with larger species generally living longer than smaller
      ones. The highest maximum lifespan recorded was 92 years in Cacatua moluccensis,
      but only 11 other species had a maximum lifespan over 50 years. Our data indicate
      that while some captive individuals are capable of reaching extraordinary ages,
      median lifespans are generally shorter than widely assumed, albeit with some
      increase seen in birds presently held in zoos. Species that lived longer and bred
      later in life tended to be more threatened according to IUCN classifications. We
      documented several individuals of multiple species that were able to breed for
      more than two decades, but the majority of clades examined had much shorter
      active reproduction periods. Post-breeding periods were surprisingly long and in
      many cases surpassed the duration of active breeding. Our results demonstrate the
      value of the ISIS database to estimate life history data for an at-risk taxon
      that is difficult to study in the wild, and provide life history data that is
      crucial for predictive modeling of future species endangerment and proactively
      managing captive populations of parrots.

PMID- 22389583
TI  - Magnetite Nanoparticles for Medical MR Imaging.
AB  - Nanotechnology has given scientists new tools for the development of advanced
      materials for the detection and diagnosis of disease. Iron oxide nanoparticles
      (SPIONs) in particular have been extensively investigated as novel magnetic
      resonance imaging (MRI) contrast agents due to a combination of favorable
      superparamagnetic properties, biodegradability, and surface properties of easy
      modification for improved in vivo kinetics and multifunctionality. This review
      discusses the basics of MR imaging, the origin of SPION's unique magnetic
      properties, recent developments in MRI acquisition methods for detection of
      SPIONs, synthesis and post-synthesis processes that improve SPION's imaging
      characteristics, and an outlook on the translational potential of SPIONs.

PMID- 22389585
TI  - A one-layer satellite surface energy balance for estimating evapotranspiration
      rates and crop water stress indexes.
AB  - Daily evapotranspiration fluxes over the semi-arid Catania Plain area (Eastern
      Sicily, Italy) were evaluated using remotely sensed data from Landsat Thematic
      Mapper TM5 images. A one-source parameterization of the surface sensible heat
      flux exchange using satellite surface temperature has been used. The transfer of
      sensible and latent heat is described by aerodynamic resistance and surface
      resistance. Required model inputs are brightness, temperature, fractional
      vegetation cover or leaf area index, albedo, crop height, roughness lengths, net
      radiation, air temperature, air humidity and wind speed. The aerodynamic
      resistance (r(ah)) is formulated on the basis of the Monin-Obukhov surface layer
      similarity theory and the surface resistance (r(s)) is evaluated from the energy
      balance equation. The instantaneous surface flux values were converted into
      evaporative fraction (EF) over the heterogeneous land surface to derive daily
      evapotranspiration values. Remote sensing-based assessments of crop water stress
      (CWSI) were also made in order to identify local irrigation requirements.
      Evapotranspiration data and crop coefficient values obtained from the approach
      were compared with: (i) data from the semi-empirical approach "K(c) reflectance
      based", which integrates satellite data in the visible and NIR regions of the
      electromagnetic spectrum with ground-based measurements and (ii) surface energy
      flux measurements collected from a micrometeorological tower located in the
      experiment area. The expected variability associated with ET flux measurements
      suggests that the approach-derived surface fluxes were in acceptable agreement
      with the observations.

PMID- 22389584
TI  - Analysis of Histone Modifications from Tryptic Peptides of Deuteroacetylated
      Isoforms.
AB  - The in vitro deuteroacetylation of histones obtained from biological sources has
      been used previously in bottom-up mass spectrometry analyses to quantitate the
      percent of endogenous acetylation of specific lysine sites and/or peptides. In
      this report, derivatization of unmodified lysine residues on histones is used in
      combination with high performance mass spectrometry, including combined HPLC
      MS/MS, to distinguish and quantitate endogenously acetylated isoforms occurring
      within the same tryptic peptide sequence and to extend this derivatization
      strategy to other post-translational modifications, specifically methylation,
      dimethylation and trimethylation. The in vitro deuteroacetylation of
      monomethylated lysine residues is observed, though dimethylated or trimethylated
      residues are not derivatised. Comparison of the relative intensities ascribed to
      the deuteroacetylated and monomethylated species with the deuteroacetylated but
      unmethylated analog, provides an opportunity to estimate the percent of
      methylation at that site. In addition to the observed fragmentation patterns, the
      very high mass accuracy available on the Orbitrap mass spectrometer can be used
      to confirm the structural isoforms, and in particular to distinguish between
      trimethylated and acetylated species.

PMID- 22389586
TI  - Full hierarchic versus non-hierarchic classification approaches for mapping
      sealed surfaces at the rural-urban fringe using high-resolution satellite data.
AB  - Since 2008 more than half of the world population is living in cities and urban
      sprawl is continuing. Because of these developments, the mapping and monitoring
      of urban environments and their surroundings is becoming increasingly important.
      In this study two object-oriented approaches for high-resolution mapping of
      sealed surfaces are compared: a standard non-hierarchic approach and a full
      hierarchic approach using both multi-layer perceptrons and decision trees as
      learning algorithms. Both methods outperform the standard nearest neighbour
      classifier, which is used as a benchmark scenario. For the multi-layer perceptron
      approach, applying a hierarchic classification strategy substantially increases
      the accuracy of the classification. For the decision tree approach a one-against
      all hierarchic classification strategy does not lead to an improvement of
      classification accuracy compared to the standard all-against-all approach. Best
      results are obtained with the hierarchic multi-layer perceptron classification
      strategy, producing a kappa value of 0.77. A simple shadow reclassification
      procedure based on characteristics of neighbouring objects further increases the
      kappa value to 0.84.

PMID- 22389587
TI  - Permanent Scatterer InSAR Analysis and Validation in the Gulf of Corinth.
AB  - The Permanent Scatterers Interferometric SAR technique (PSInSAR) is a method that
      accurately estimates the near vertical terrain deformation rates, of the order of
      ~1 mm year(-1), overcoming the physical and technical restrictions of classic
      InSAR. In this paper the method is strengthened by creating a robust processing
      chain, incorporating PSInSAR analysis together with algorithmic adaptations for
      Permanent Scatterer Candidates (PSCs) and Permanent Scatterers (PSs) selection.
      The processing chain, called PerSePHONE, was applied and validated in the
      geophysically active area of the Gulf of Corinth. The analysis indicated a clear
      subsidence trend in the north-eastern part of the gulf, with the maximum
      deformation of ~2.5 mm year(-1) occurring in the region north of the Gulf of
      Alkyonides. The validity of the results was assessed against
      geophysical/geological and geodetic studies conducted in the area, which include
      continuous seismic profiling data and GPS height measurements. All these
      observations converge to the same deformation pattern as the one derived by the
      PSInSAR technique.

PMID- 22389588
TI  - Clock synchronization in wireless sensor networks: an overview.
AB  - The development of tiny, low-cost, low-power and multifunctional sensor nodes
      equipped with sensing, data processing, and communicating components, have been
      made possible by the recent advances in micro-electro-mechanical systems (MEMS)
      technology. Wireless sensor networks (WSNs) assume a collection of such tiny
      sensing devices connected wirelessly and which are used to observe and monitor a
      variety of phenomena in the real physical world. Many applications based on these
      WSNs assume local clocks at each sensor node that need to be synchronized to a
      common notion of time. This paper reviews the existing clock synchronization
      protocols for WSNs and the methods of estimating clock offset and clock skew in
      the most representative clock synchronization protocols for WSNs.

PMID- 22389589
TI  - Preparation of Surface Adsorbed and Impregnated Multi-walled Carbon
      Nanotube/Nylon-6 Nanofiber Composites and Investigation of their Gas Sensing
      Ability.
AB  - We have prepared electrospun Nylon-6 nanofibers via electrospinning, and adsorbed
      multi-walled carbon nanotubes (MWCNTs) onto the surface of Nylon-6 fibers using
      Triton((r)) X-100 to form a MWCNTs/Nylon-6 nanofiber composite. The dispersed
      MWCNTs have been found to be stable in hexafluoroisopropanol for several months
      without precipitation. A MWCNTs/Nylon-6 nanofiber composite based chemical sensor
      has demonstrated its responsiveness towards a wide range of solvent vapours at
      room temperature and only mg quantities of MWCNTs were expended. The large
      surface area and porous nature of the electrospun Nylon-6/MWCNT nanofibers
      facilitates greater analyte permeability. The experimental analysis has indicated
      that the dipole moment, functional group and vapour pressure of the analytes
      determine the magnitude of the responsiveness.

PMID- 22389590
TI  - MAPSAR Image Simulation Based on L-band Polarimetric Data from the SAR-R99B
      Airborne Sensor (SIVAM System).
AB  - This paper describes the methodology applied to generate simulated multipolarized
      L-band SAR images of the MAPSAR (Multi-Application Purpose SAR) satellite from
      the airborne SAR R99B sensor (SIVAM System). MAPSAR is a feasibility study
      conducted by INPE (National Institute for Space Research) and DLR (German
      Aerospace Center) targeting a satellite L-band SAR innovative mission for
      assessment, management and monitoring of natural resources. Examples of simulated
      products and their applications are briefly discussed.

PMID- 22389591
TI  - Effect of Structural Design of Silver/Silver Chloride Electrodes on Stability and
      Response Time and the Implications for Improved Accuracy in pH Measurement.
AB  - The response time of thermal electrolytic Ag/AgCl reference electrodes is defined
      by the porous structure that limits the rate at which traces of any previous
      solution are diluted by any new solution environment. The electrode stabilisation
      time when transferred from one electrolyte to another has been shown to change
      when different structural designs to the conventional sphere of Ag/AgCl are used.
      Electrodes fabricated with cylindrical architectures of Ag/AgCl have shown
      improved stability and reach equilibrium faster than spherical electrodes. This
      work has positive implications for the accuracy and throughput of primary pH
      measurements made using the Harned cell.

PMID- 22389592
TI  - 1T Pixel Using Floating-Body MOSFET for CMOS Image Sensors.
AB  - We present a single-transistor pixel for CMOS image sensors (CIS). It is a
      floating-body MOSFET structure, which is used as photo-sensing device and source
      follower transistor, and can be controlled to store and evacuate charges. Our
      investigation into this 1T pixel structure includes modeling to obtain analytical
      description of conversion gain. Model validation has been done by comparing
      theoretical predictions and experimental results. On the other hand, the 1T pixel
      structure has been implemented in different configurations, including rectangular
      gate and ring-gate designs, and variations of oxidation parameters for the
      fabrication process. The pixel characteristics are presented and discussed.

PMID- 22389593
TI  - Remote sensing data with the conditional latin hypercube sampling and
      geostatistical approach to delineate landscape changes induced by large
      chronological physical disturbances.
AB  - This study applies variogram analyses of normalized difference vegetation index
      (NDVI) images derived from SPOT HRV images obtained before and after the ChiChi
      earthquake in the Chenyulan watershed, Taiwan, as well as images after four large
      typhoons, to delineate the spatial patterns, spatial structures and spatial
      variability of landscapes caused by these large disturbances. The conditional
      Latin hypercube sampling approach was applied to select samples from multiple
      NDVI images. Kriging and sequential Gaussian simulation with sufficient samples
      were then used to generate maps of NDVI images. The variography of NDVI image
      results demonstrate that spatial patterns of disturbed landscapes were
      successfully delineated by variogram analysis in study areas. The high-magnitude
      Chi-Chi earthquake created spatial landscape variations in the study area. After
      the earthquake, the cumulative impacts of typhoons on landscape patterns depended
      on the magnitudes and paths of typhoons, but were not always evident in the
      spatiotemporal variability of landscapes in the study area. The statistics and
      spatial structures of multiple NDVI images were captured by 3,000 samples from
      62,500 grids in the NDVI images. Kriging and sequential Gaussian simulation with
      the 3,000 samples effectively reproduced spatial patterns of NDVI images.
      However, the proposed approach, which integrates the conditional Latin hypercube
      sampling approach, variogram, kriging and sequential Gaussian simulation in
      remotely sensed images, efficiently monitors, samples and maps the effects of
      large chronological disturbances on spatial characteristics of landscape changes
      including spatial variability and heterogeneity.

PMID- 22389594
TI  - Effects of orbit and pointing geometry of a spaceborne formation for monostatic
      bistatic radargrammetry on terrain elevation measurement accuracy.
AB  - During the last decade a methodology for the reconstruction of surface relief by
      Synthetic Aperture Radar (SAR) measurements - SAR interferometry - has become a
      standard. Different techniques developed before, such as stereo-radargrammetry,
      have been experienced from space only in very limiting geometries and time
      series, and, hence, branded as less accurate. However, novel formation flying
      configurations achievable by modern spacecraft allow fulfillment of SAR missions
      able to produce pairs of monostatic-bistatic images gathered simultaneously, with
      programmed looking angles. Hence it is possible to achieve large antenna
      separations, adequate for exploiting to the utmost the stereoscopic effect, and
      to make negligible time decorrelation, a strong liming factor for repeat-pass
      stereo-radargrammetric techniques. This paper reports on design of a monostatic
      bistatic mission, in terms of orbit and pointing geometry, and taking into
      account present generation SAR and technology for accurate relative navigation.
      Performances of different methods for monostatic-bistatic stereo-radargrammetry
      are then evaluated, showing the possibility to determine the local surface relief
      with a metric accuracy over a wide range of Earth latitudes.

PMID- 22389595
TI  - Multi-channel morphological profiles for classification of hyperspectral images
      using support vector machines.
AB  - Hyperspectral imaging is a new remote sensing technique that generates hundreds
      of images, corresponding to different wavelength channels, for the same area on
      the surface of the Earth. Supervised classification of hyperspectral image data
      sets is a challenging problem due to the limited availability of training samples
      (which are very difficult and costly to obtain in practice) and the extremely
      high dimensionality of the data. In this paper, we explore the use of multi
      channel morphological profiles for feature extraction prior to classification of
      remotely sensed hyperspectral data sets using support vector machines (SVMs). In
      order to introduce multi-channel morphological transformations, which rely on
      ordering of pixel vectors in multidimensional space, several vector ordering
      strategies are investigated. A reduced implementation which builds the multi
      channel morphological profile based on the first components resulting from a
      dimensional reduction transformation applied to the input data is also proposed.
      Our experimental results, conducted using three representative hyperspectral data
      sets collected by NASA's Airborne Visible-Infrared Imaging Spectrometer (AVIRIS)
      sensor and the German Digital Airborne Imaging Spectrometer (DAIS 7915), reveal
      that multi-channel morphological profiles can improve single-channel
      morphological profiles in the task of extracting relevant features for
      classification of hyperspectral data using small training sets.

PMID- 22389596
TI  - Determination of Antimony (III) in Real Samples by Anodic Stripping Voltammetry
      Using a Mercury Film Screen-Printed Electrode.
AB  - This paper describes a procedure for the determination of antimony (III) by
      differential pulse anodic stripping voltammetry using a mercury film screen
      printed electrode as the working electrode. The procedure has been optimized
      using experimental design methodology. Under these conditions, in terms of
      Residual Standard Deviation (RSD), the repeatability (3.81 %) and the
      reproducibility (5.07 %) of the constructed electrodes were both analyzed. The
      detection limit for Sb (III) was calculated at a value of 1.27*10(-8) M. The
      linear range obtained was between 0.99 * 10(-8) - 8.26 * 10(-8) M. An analysis of
      possible effects due to the presence of foreign ions in the solution was
      performed and the procedure was successfully applied to the determination of
      antimony levels in pharmaceutical preparations and sea water samples.

PMID- 22389597
TI  - Simulation of greenhouse climate monitoring and control with wireless sensor
      network and event-based control.
AB  - Monitoring and control of the greenhouse environment play a decisive role in
      greenhouse production processes. Assurance of optimal climate conditions has a
      direct influence on crop growth performance, but it usually increases the
      required equipment cost. Traditionally, greenhouse installations have required a
      great effort to connect and distribute all the sensors and data acquisition
      systems. These installations need many data and power wires to be distributed
      along the greenhouses, making the system complex and expensive. For this reason,
      and others such as unavailability of distributed actuators, only individual
      sensors are usually located in a fixed point that is selected as representative
      of the overall greenhouse dynamics. On the other hand, the actuation system in
      greenhouses is usually composed by mechanical devices controlled by relays, being
      desirable to reduce the number of commutations of the control signals from
      security and economical point of views. Therefore, and in order to face these
      drawbacks, this paper describes how the greenhouse climate control can be
      represented as an event-based system in combination with wireless sensor
      networks, where low-frequency dynamics variables have to be controlled and
      control actions are mainly calculated against events produced by external
      disturbances. The proposed control system allows saving costs related with wear
      minimization and prolonging the actuator life, but keeping promising performance
      results. Analysis and conclusions are given by means of simulation results.

PMID- 22389598
TI  - HyBloc: Localization in Sensor Networks with Adverse Anchor Placement.
AB  - To determine the geographical positions of sensors, numerous localization
      algorithms have been proposed in recent years. The positions of sensors are
      inferred from the connectivity between sensors and a set of nodes called anchors
      which know their precise locations. We investigate the effect of adverse
      placement and density of anchors on the accuracies of different algorithms. We
      develop an algorithm called HyBrid Localization (HyBloc) to provide reliable
      localization service with a limited number of clustered anchors. HyBloc is
      distributed in nature with reasonable message overhead. Through simulations, we
      demonstrate that HyBloc provides more accurate location estimates than some
      existing distributed algorithms when there are only a few anchors. HyBloc also
      performs well when anchors are clustered together.

PMID- 22389599
TI  - A localized coverage preserving protocol for wireless sensor networks.
AB  - In a randomly deployed and large scale wireless sensor network, coverage
      redundant nodes consume much unnecessary energy. As a result, turning off these
      redundant nodes can prolong the network lifetime, while maintaining the degree of
      sensing coverage with a limited number of on-duty nodes. None of the off-duty
      eligibility rules in the literature, however, are sufficient and necessary
      conditions for eligible nodes. Hence redundancy or blind points might be
      incurred. In this paper we propose a complete Eligibility Rule based on Perimeter
      Coverage (ERPC) for a node to determine its eligibility for sleeping. ERPC has a
      computational complexity of O(N(2)log(N)), lower than the eligibility rule in the
      Coverage Control Protocol (CCP), O(N(3)), where N is the number of neighboring
      nodes. We then present a Coverage Preserving Protocol (CPP) to schedule the work
      state of eligible nodes. The main advantage of CPP over the Ottawa protocol lies
      in its ability to configure the network to any specific coverage degree, while
      the Ottawa protocol does not support different coverage configuration. Moreover,
      as a localized protocol, CPP has better adaptability to dynamic topologies than
      centralized protocols. Simulation results indicate that CPP can preserve network
      coverage with fewer active nodes than the Ottawa protocol. In addition, CPP is
      capable of identifying all the eligible nodes exactly while the CCP protocol
      might result in blind points due to error decisions. Quantitative analysis and
      experiments demonstrate that CPP can extend the network lifetime significantly
      while maintaining a given coverage degree.

PMID- 22389600
TI  - Algorithmic foundation of spectral rarefaction for measuring satellite imagery
      heterogeneity at multiple spatial scales.
AB  - Measuring heterogeneity in satellite imagery is an important task to deal with.
      Most measures of spectral diversity have been based on Shannon Information
      theory. However, this approach does not inherently address different scales,
      ranging from local (hereafter referred to alpha diversity) to global scales
      (gamma diversity). The aim of this paper is to propose a method for measuring
      spectral heterogeneity at multiple scales based on rarefaction curves. An
      algorithmic solution of rarefaction applied to image pixel values (Digital
      Numbers, DNs) is provided and discussed.

PMID- 22389601
TI  - Emission characteristics and factors of selected odorous compounds at a
      wastewater treatment plant.
AB  - THIS STUDY WAS INITIATED TO EXPLORE THE EMISSION CHARACTERISTICS OF REDUCED
      SULFUR COMPOUNDS (RSCS: hydrogen sulfide, methyl mercaptan, dimethyl sulfide,
      dimethyl disulfide), ammonia and trimethylamine from a Wastewater Treatment Plant
      (WWTP) located at Sun-Cheon, Chonlanam-Do in South Korea. The study also
      evaluates flux profiles of the six selected odorous compounds and their flux
      rates (MUg/m(2)/min) and compares their emission characteristics. A Dynamic Flux
      Chamber DFC was used to measure fluxes of pollutants from the treatment plant.
      Quality control of odor samples using a non-reactive sulfur dioxide gas
      determined the time taken for DFC concentration to reach equilibrium. The reduced
      sulfur compounds were analyzed by interfacing gas chromatography with a Pulsed
      Flame Photometric Detector (PFPD). Air samples were collected in the morning and
      afternoon on one day during summer (August) and two days in winter (December and
      January). Their emission rates were determined and it was observed that during
      summer relatively higher amounts of the selected odorous compounds were emitted
      compared to winter. Air samples from primary settling basin, aeration basin, and
      final settling basin were tested and the total amount of selected odorous
      compounds emitted per wastewater ton was found to be 1344 MUg/m(3) from the
      selected treatment processes. It was also observed that, in this study, the
      dominant odor intensity contribution was caused by dimethyl disulfide (69.1%).

PMID- 22389602
TI  - An effective mobile sensor control method for sparse sensor networks.
AB  - In this paper, we propose an effective mobile sensor control method, named DATFM
      (Data Acquisition and Transmission with Fixed and Mobile node) for sparse sensor
      networks. DATFM uses two types of sensor nodes, fixed node and mobile node. The
      data acquired by nodes are accumulated on a fixed node before being transferred
      to the sink node. In addition, DATFM transfers the accumulated data efficiently
      by constructing a communication route of multiple mobile nodes between fixed
      nodes. We also conduct simulation experiments to evaluate the performance of
      DATFM.

PMID- 22389603
TI  - Evaluation of the Convergence Region of an Automated Registration Method for 3D
      Laser Scanner Point Clouds.
AB  - Using three dimensional point clouds from both simulated and real datasets from
      close and terrestrial laser scanners, the rotational and translational
      convergence regions of Geometric Primitive Iterative Closest Points (GP-ICP) are
      empirically evaluated. The results demonstrate the GP-ICP has a larger rotational
      convergence region than the existing methods, e.g., the Iterative Closest Point
      (ICP).

PMID- 22389606
TI  - Immobilization of electroporated cells for fabrication of cellular biosensors:
      physiological effects of the shape of calcium alginate matrices and foetal calf
      serum.
AB  - In order to investigate the physiological effect of transfected cell
      immobilization in calcium alginate gels, we immobilized electroporated Vero cells
      in gels shaped either as spherical beads or as thin membrane layers. In addition,
      we investigated whether serum addition had a positive effect on cell
      proliferation and viability in either gel configuration. The gels were stored for
      four weeks in a medium supplemented or not with 20% (v/v) foetal calf serum.
      Throughout a culture period of four weeks, cell proliferation and cell viability
      were assayed by optical microscopy after provision of Trypan Blue. Non-elaborate
      culture conditions (room temperature, non-CO(2) enriched culture atmosphere) were
      applied throughout the experimental period in order to evaluate cell viability
      under less than optimal storage conditions. Immobilization of electroporated
      cells was associated with an initially reduced cell viability, which was
      gradually increased. Immobilization was associated with maintenance of cell
      growth for the duration of the experimental period, whereas electroporated cells
      essentially died after a week in suspension culture. Considerable proliferation
      of immobilized cells was observed in spherical alginate beads. In both gel
      configurations, addition of serum was associated with increased cell
      proliferation. The results of the present study could contribute to an
      improvement of the storability of biosensors based on electroporated, genetically
      or membrane-engineered cells.

PMID- 22389607
TI  - Human NK Cell Up-regulation of CD69, HLA-DR, Interferon gamma Secretion and
      Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through
      Overlapping but Different Pathways.
AB  - Human plasmacytoid dendritic cells secrete high levels of IFNalpha and are thus
      implicated in the activation of NK cells. Activated NK cells are characterised by
      the up-regulation of CD69 and MHC class II DR expression, secretion of IFN gamma
      and enhanced cytotoxicity. We show that pDC mediate these processes by different
      mechanisms, some of which overlap. Human NK cells were analysed after co-culture
      with immature or CpG-matured blood pDC or with supernatant from these cells.
      Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC
      and did not require pDC contact. Up-regulation was due in part to IFNalpha but
      also to factors in IFNalpha negative supernatant from immature DC. HLA-DR
      expression was independent of secreted molecules but required contact with
      immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562
      targets and expression of CD107a, was mediated by multiple factors including type
      I IFN, supernatant from immature pDC cultures and contact with immature or mature
      pDC. These factors act cumulatively to enhance cytotoxcity. Thus different
      parameters of pDC mediated NK cell activation are regulated by distinct pathways.

PMID- 22389608
TI  - A Differential Pressure Instrument with Wireless Telemetry for In-Situ
      Measurement of Fluid Flow across Sediment-Water Boundaries.
AB  - An instrument has been built to carry out continuous in-situ measurement of small
      differences in water pressure, conductivity and temperature, in natural surface
      water and groundwater systems. A low-cost data telemetry system provides data on
      shore in real time if desired. The immediate purpose of measurements by this
      device is to continuously infer fluxes of water across the sediment-water
      interface in a complex estuarine system; however, direct application to
      assessment of sediment-water fluxes in rivers, lakes, and other systems is also
      possible. Key objectives of the design include both low cost, and accuracy of the
      order of +/-0.5 mm H(2)O in measured head difference between the instrument's two
      pressure ports. These objectives have been met, although a revision to the design
      of one component was found to be necessary. Deployments of up to nine months, and
      wireless range in excess of 300 m have been demonstrated.

PMID- 22389609
TI  - CMOS Image Sensors for High Speed Applications.
AB  - Recent advances in deep submicron CMOS technologies and improved pixel designs
      have enabled CMOS-based imagers to surpass charge-coupled devices (CCD) imaging
      technology for mainstream applications. The parallel outputs that CMOS imagers
      can offer, in addition to complete camera-on-a-chip solutions due to being
      fabricated in standard CMOS technologies, result in compelling advantages in
      speed and system throughput. Since there is a practical limit on the minimum
      pixel size (4~5 MUm) due to limitations in the optics, CMOS technology scaling
      can allow for an increased number of transistors to be integrated into the pixel
      to improve both detection and signal processing. Such smart pixels truly show the
      potential of CMOS technology for imaging applications allowing CMOS imagers to
      achieve the image quality and global shuttering performance necessary to meet the
      demands of ultrahigh-speed applications. In this paper, a review of CMOS-based
      high-speed imager design is presented and the various implementations that target
      ultrahigh-speed imaging are described. This work also discusses the design,
      layout and simulation results of an ultrahigh acquisition rate CMOS active-pixel
      sensor imager that can take 8 frames at a rate of more than a billion frames per
      second (fps).

PMID- 22389610
TI  - An energy-aware routing protocol in wireless sensor networks.
AB  - The most important issue that must be solved in designing a data gathering
      algorithm for wireless sensor networks (WSNS) is how to save sensor node energy
      while meeting the needs of applications/users. In this paper, we propose a novel
      energy-aware routing protocol (EAP) for a long-lived sensor network. EAP achieves
      a good performance in terms of lifetime by minimizing energy consumption for in
      network communications and balancing the energy load among all the nodes. EAP
      introduces a new clustering parameter for cluster head election, which can better
      handle the heterogeneous energy capacities. Furthermore, it also introduces a
      simple but efficient approach, namely, intra-cluster coverage to cope with the
      area coverage problem. We use a simple temperature sensing application to
      evaluate the performance of EAP and results show that our protocol significantly
      outperforms LEACH and HEED in terms of network lifetime and the amount of data
      gathered.

PMID- 22389611
TI  - Influence of Surface Roughness Spatial Variability and Temporal Dynamics on the
      Retrieval of Soil Moisture from SAR Observations.
AB  - Radar-based surface soil moisture retrieval has been subject of intense research
      during the last decades. However, several difficulties hamper the operational
      estimation of soil moisture based on currently available spaceborne sensors. The
      main difficulty experienced so far results from the strong influence of other
      surface characteristics, mainly roughness, on the backscattering coefficient,
      which hinders the soil moisture inversion. This is especially true for single
      configuration observations where the solution to the surface backscattering
      problem is ill-posed. Over agricultural areas cultivated with winter cereal
      crops, roughness can be assumed to remain constant along the growing cycle
      allowing the use of simplified approaches that facilitate the estimation of the
      moisture content of soils. However, the field scale spatial variability and
      temporal variations of roughness can introduce errors in the estimation of soil
      moisture that are difficult to evaluate. The objective of this study is to assess
      the impact of roughness spatial variability and roughness temporal variations on
      the retrieval of soil moisture from radar observations. A series of laser
      profilometer measurements were performed over several fields in an experimental
      watershed from September 2004 to March 2005. The influence of the observed
      roughness variability and its temporal variations on the retrieval of soil
      moisture is studied using simulations performed with the Integral Equation Model,
      considering different sensor configurations. Results show that both field scale
      roughness spatial variability and its temporal variations are aspects that need
      to be taken into account, since they can introduce large errors on the retrieved
      soil moisture values.

PMID- 22389612
TI  - Multi-Line Fit Model for the Detection of Methane at nu(2) + 2nu(3) Band using
      Hollow-Core Photonic Bandgap Fibres.
AB  - Hollow-core photonic bandgap fibres (HC-PBFs) have emerged as a novel technology
      in the field of gas sensing. The long interaction pathlengths achievable with
      these fibres are especially advantageous for the detection of weakly absorbing
      gases. In this work, we demonstrate the good performance of a HC-PBF in the
      detection of the nu(2) + 2nu(3) band of methane, at 1.3 MUm. The Q-branch
      manifold, at 1331.55 nm, is targeted for concentration monitoring purposes. A
      computationally optimized multi-line model is used to fit the Q-branch. Using
      this model, a detection limit of 98 ppmv (parts per million by volume) is
      estimated.

PMID- 22389613
TI  - A study of ground deformation in the guangzhou urban area with persistent
      scatterer interferometry.
AB  - The Interferometric Point Target Analysis (IPTA) technique and Advanced Synthetic
      Aperture Radar (ASAR) images acquired over Hong Kong from 2007-2008 were used to
      detect ground deformation in the urban area of Guangzhou city in South China. A
      ground deformation rate map with scattered distribution of point targets shows
      the maximum subsidence (rise) rate as high as -26 to -20 mma(-1) (16-21 mma(-1)),
      implying that the study area is an active zone for ground deformation. Based on
      the point target map, a contour ground deformation rate map is generated. The map
      shows three major subsidence zones located in the middle-west, the east, and the
      southwest of the study area, respectively. All the six ground collapse accidents
      that occurred in 2007-2008 fall within the subsidence zones, qualitatively
      validating the IPTA results. Ground subsidence and geological conditions on
      Datansha Island are examined. The results indicate that the local geological
      conditions, such as limestone Karst geomorphology as well as silt layers
      characterized by high water content, high void ratio, high compressibility, low
      bearing capacity and low shear strength, and underground engineering projects are
      responsible for ground subsidence and ground collapse accidents occurred there.

PMID- 22389614
TI  - Sensitivity improvement of a humidity sensor based on silica nanospheres on a
      long-period fiber grating.
AB  - This work addresses a new configuration that improves the sensitivity of a
      humidity sensor based on a long-period fiber grating coated with a SiO(2)
      nanospheres film. An intermediate higher refractive index overlay, deposited
      through Electrostatic Self-Assembly, is placed between the fiber cladding and the
      humidity sensitive film in order to increase the total effective refractive index
      of the coating. With this intermediate design, a three-fold improvement in the
      sensitivity was obtained. Wavelength shifts up to 15 nm against 5 nm were
      achieved in a humidity range from 20% to 80%.

PMID- 22389615
TI  - Simultaneous Measurements of Chlorophyll Concentration by Lidar, Fluorometry,
      above-Water Radiometry, and Ocean Color MODIS Images in the Southwestern
      Atlantic.
AB  - Comparisons between in situ measurements of surface chlorophyll-a concentration
      (CHL) and ocean color remote sensing estimates were conducted during an
      oceanographic cruise on the Brazilian Southeastern continental shelf and slope,
      Southwestern South Atlantic. In situ values were based on fluorometry, above
      water radiometry and lidar fluorosensor. Three empirical algorithms were used to
      estimate CHL from radiometric measurements: Ocean Chlorophyll 3 bands
      (OC3M(RAD)), Ocean Chlorophyll 4 bands (OC4v4(RAD)), and Ocean Chlorophyll 2
      bands (OC2v4(RAD)). The satellite estimates of CHL were derived from data
      collected by the MODerate-resolution Imaging Spectroradiometer (MODIS) with a
      nominal 1.1 km resolution at nadir. Three algorithms were used to estimate
      chlorophyll concentrations from MODIS data: one empirical - OC3M(SAT), and two
      semi-analytical - Garver, Siegel, Maritorena version 01 (GSM01(SAT)), and
      Carder(SAT). In the present work, MODIS, lidar and in situ above-water radiometry
      and fluorometry are briefly described and the estimated values of chlorophyll
      retrieved by these techniques are compared. The chlorophyll concentration in the
      study area was in the range 0.01 to 0.2 mg/m(3). In general, the empirical
      algorithms applied to the in situ radiometric and satellite data showed a
      tendency to overestimate CHL with a mean difference between estimated and
      measured values of as much as 0.17 mg/m(3) (OC2v4(RAD)). The semi-analytical
      GSM01 algorithm applied to MODIS data performed better (rmse 0.28, rmse-L 0.08,
      mean diff. -0.01 mg/m(3)) than the Carder and the empirical OC3M algorithms (rmse
      1.14 and 0.36, rmse-L 0.34 and 0.11, mean diff. 0.17 and 0.02 mg/m(3),
      respectively). We find that rmsd values between MODIS relative to the in situ
      radiometric measurements are < 26%, i.e., there is a trend towards overestimation
      of R(RS) by MODIS for the stations considered in this work. Other authors have
      already reported over and under estimation of MODIS remotely sensed reflectance
      due to several errors in the bio-optical algorithm performance, in the satellite
      sensor calibration, and in the atmospheric-correction algorithm.

PMID- 22389616
TI  - Ricin detection using phage displayed single domain antibodies.
AB  - Phage-displayed single domain antibodies (sdAb) were compared to monomeric
      solubly expressed sdAb and llama polyclonal antibodies for the detection of
      ricin. SdAb are comprised of the variable domain derived from camelid heavy chain
      only antibodies (HcAb). Although HcAb lack variable light chains, they as well as
      their derivative sdAb are able to bind antigens with high affinity. The small
      size of sdAb (~16 kDa), while advantageous in many respects, limits the number of
      labels that can be incorporated. The ability to incorporate multiple labels is a
      beneficial attribute for reporter elements. Opportunely, sdAb are often selected
      using phage display methodology. Using sdAb displayed on bacteriophage M13 as the
      reporter element gives the potential for incorporating a very high number of
      labels. We have demonstrated the use of both sdAb and phage- displayed sdAb for
      the detection of ricin using both enzyme linked immunosorbent assays (ELISAs) and
      Luminex fluid array assays. The phage-displayed sdAb led to five to ten fold
      better detection of ricin in both the ELISA and Luminex assays, resulting in
      limits of detection of 1 ng/mL and 64 pg/mL respectively. The phage-displayed
      sdAb were also dramatically more effective for the visualization of binding to
      target in nitrocellulose dot blot assays, a method frequently used for epitope
      mapping.

PMID- 22389617
TI  - Modeling Impact-induced Failure of Polysilicon MEMS: A Multi-scale Approach.
AB  - Failure of packaged polysilicon micro-electro-mechanical systems (MEMS) subjected
      to impacts involves phenomena occurring at several length-scales. In this paper
      we present a multi-scale finite element approach to properly allow for: (i) the
      propagation of stress waves inside the package; (ii) the dynamics of the whole
      MEMS; (iii) the spreading of micro-cracking in the failing part(s) of the sensor.
      Through Monte Carlo simulations, some effects of polysilicon micro-structure on
      the failure mode are elucidated.

PMID- 22389618
TI  - State-of-The-Art and Applications of 3D Imaging Sensors in Industry, Cultural
      Heritage, Medicine, and Criminal Investigation.
AB  - 3D imaging sensors for the acquisition of three dimensional (3D) shapes have
      created, in recent years, a considerable degree of interest for a number of
      applications. The miniaturization and integration of the optical and electronic
      components used to build them have played a crucial role in the achievement of
      compactness, robustness and flexibility of the sensors. Today, several 3D sensors
      are available on the market, even in combination with other sensors in a "sensor
      fusion" approach. An importance equal to that of physical miniaturization has the
      portability of the measurements, via suitable interfaces, into software
      environments designed for their elaboration, e.g., CAD-CAM systems, virtual
      renders, and rapid prototyping tools. In this paper, following an overview of the
      state-of-art of 3D imaging sensors, a number of significant examples of their use
      are presented, with particular reference to industry, heritage, medicine, and
      criminal investigation applications.

PMID- 22389619
TI  - An Approach for Rapid Assessment of Seismic Hazards in Turkey by Continuous GPS
      Data.
AB  - The Earth is being monitored every day by all kinds of sensors. This leads an
      overflow of data in all branches of science nowadays, especially in Earth
      Sciences. Data storage and data processing are the problems to be solved by
      current technologies, as well as by those accessing and analyzing these large
      data sources. Once solutions have been created for collecting, storing and
      accessing data, then the challenge becomes how to effectively share data,
      applications and processing resources across many locations. The Global
      Positioning System (GPS) sensors are being used as geodetic instruments to
      precisely detect crustal motion in the Earth's surface. Rapid access to data
      provided by GPS sensors is becoming increasingly important for deformation
      monitoring and rapid hazard assessments. Today, reliable and fast collection and
      distribution of data is a challenge and advances in Internet technologies have
      made it easier to provide the needed data. This study describes a system which
      will be able to generate strain maps using data from continuous GPS stations for
      seismic hazard analysis. Strain rates are a key factor in seismic hazard
      analyses. Turkey is a country prone to earthquakes with a long history of seismic
      hazards and disasters. This situation has resulted in the studies by Earth
      scientists that focus on Turkey in order to improve their understanding of the
      Earth's crust structure and seismic hazards. Nevertheless, the construction of
      models, data access and analysis are often not fast as expected, but the
      combination of Internet technologies with continuous GPS sensors can be a
      solution to overcome this problem. This system would have the potential to answer
      many important questions to assess seismic hazards such as how much stretching,
      squashing and shearing is taking place in different parts of Turkey, and how do
      velocities change from place to place? Seismic hazard estimation is the most
      effective way to reduce earthquake losses. It is clear that reliability of data
      and on-line services will support the preparation of strategies for disaster
      management and planning to cope with hazards.

PMID- 22389620
TI  - Observation of a Large Landslide on La Reunion Island Using Differential Sar
      Interferometry (JERS and Radarsat) and Correlation of Optical (Spot5 and Aerial)
      Images.
AB  - Slope instabilities are one of the most important geo-hazards in terms of socio
      economic costs. The island of La Reunion (Indian Ocean) is affected by constant
      slope movements and huge landslides due to a combination of rough topography, wet
      tropical climate and its specific geological context. We show that remote sensing
      techniques (Differential SAR Interferometry and correlation of optical images)
      provide complementary means to characterize landslides on a regional scale. The
      vegetation cover generally hampers the analysis of C-band interferograms. We used
      JERS-1 images to show that the L-band can be used to overcome the loss of
      coherence observed in Radarsat C-band interferograms. Image correlation was
      applied to optical airborne and SPOT 5 sensors images. The two techniques were
      applied to a landslide near the town of Hellbourg in order to assess their
      performance for detecting and quantifying the ground motion associated to this
      landslide. They allowed the mapping of the unstable areas. Ground displacement of
      about 0.5 m yr(-1) was measured.

PMID- 22389621
TI  - A two-dimensional micro scanner integrated with a piezoelectric actuator and
      piezoresistors.
AB  - A compact two-dimensional micro scanner with small volume, large deflection
      angles and high frequency is presented and the two-dimensional laser scanning is
      achieved by specular reflection. To achieve large deflection angles, the micro
      scanner excited by a piezoelectric actuator operates in the resonance mode. The
      scanning frequencies and the maximum scanning angles of the two degrees of
      freedom are analyzed by modeling and simulation of the structure. For the
      deflection angle measurement, piezoresistors are integrated in the micro scanner.
      The appropriate directions and crystal orientations of the piezoresistors are
      designed to obtain the large piezoresistive coefficients for the high
      sensitivities. Wheatstone bridges are used to measure the deflection angles of
      each direction independently and precisely. The scanner is fabricated and
      packaged with the piezoelectric actuator and the piezoresistors detection
      circuits in a size of 28 mm*20 mm*18 mm. The experiment shows that the two
      scanning frequencies are 216.8 Hz and 464.8 Hz, respectively. By an actuation
      displacement of 10 MUm, the scanning range of the two-dimensional micro scanner
      is above 26 degrees  * 23 degrees . The deflection angle measurement
      sensitivities for two directions are 59 mV/deg and 30 mV/deg, respectively.

PMID- 22389622
TI  - Reduction of Non-Specific Protein Adsorption Using Poly(ethylene) Glycol (PEG)
      Modified Polyacrylate Hydrogels In Immunoassays for Staphylococcal Enterotoxin B
      Detection.
AB  - Three PEG molecules (PEG-methacrylate, -diacrylate and -dimethacrylate) were
      incorporated into galactose-based polyacrylate hydrogels and their relative
      abilities to reduce non-specific protein adsorption in immunoassays were
      determined. Highly crosslinked hydrogels containing amine-terminated
      functionalities were formed and used to covalently attach antibodies specific for
      staphylococcal enterotoxin B (SEB). Patterned arrays of immobilized antibodies in
      the PEG-modified hydrogels were created with a PDMS template containing micro
      channels for use in sandwich immunoassays to detect SEB. Different concentrations
      of the toxin were applied to the hydrogel arrays, followed with a Cy3-labeled
      tracer antibody specific for the two toxins. Fluorescence laser scanning confocal
      microscopy of the tracer molecules provided both qualitative and quantitative
      measurements on the detection sensitivity and the reduction in non-specific
      binding as a result of PEG incorporation. Results showed the PEG-modified
      hydrogel significantly reduced non-specific protein binding with a detection
      limit for SEB of 1 ng/mL. Fluorescence signals showed a 10-fold decrease in the
      non-specific binding and a 6-fold increase in specific binding of SEB.

PMID- 22389623
TI  - Use of reflectance ratios as a proxy for coastal water constituent monitoring in
      the pearl river estuary.
AB  - Spectra, salinity, total suspended solids (TSS, in mg/L) and colored dissolved
      organic matter (CDOM, ag(400) at 400 nm) sampled in stations in 44 different
      locations on December 18, 19 and 21, in 2006 were measured and analyzed. The
      studied field covered a large variety of optically different waters, the
      absorption coefficient of CDOM ([ag(400)] in m(-1)) varied between 0.488 and 1.41
      m(-1), and the TSS concentrations (mg/L) varied between 7.0 and 241.1 mg/L. In
      order to detect salinity of the Pearl River Estuary, we analyzed the spectral
      properties of TSS and CDOM, and the relationships between field water reflectance
      spectra and water constituents' concentrations based on the synchronous in-situ
      and satellite hyper-spectral image analysis. A good correlation was discovered
      (the positive correlation by linear fit), between in-situ reflectance ratio
      R(680)/R(527) and TSS concentrations (R(2) = 0.65) for the salinity range of 1.74
      22.12. However, the result also showed that the absorption coefficient of CDOM
      was not tightly correlated with reflectance. In addition, we also observed two
      significant relationships (R(2) > 0.77), one between TSS concentrations and
      surface salinity and the other between the absorption coefficient of CDOM and
      surface salinity. Finally, we develop a novel method to understand surface
      salinity distribution of estuarine waters from the calibrated EO-1 Hyperion
      reflectance data in the Pearl River Estuary, i.e. channels with high salinity and
      shoals with low salinity. The EO-1 Hyperion derived surface salinity and TSS
      concentrations were validated using in-situ data that were collected on December
      21, 2006, synchronous with EO-1 Hyperion satellite imagery acquisition. The
      results showed that the semi-empirical relationships are capable of predicting
      salinity from EO-1 Hyperion imagery in the Pearl River Estuary (RMSE < 20/00).

PMID- 22389624
TI  - Applications of nanomaterials in electrogenerated chemiluminescence biosensors.
AB  - Electrogenerated chemiluminescence (also called electrochemiluminescence and
      abbreviated ECL) involves the generation of species at electrode surfaces that
      then undergo electron-transfer reactions to form excited states that emit light.
      ECL biosensor, combining advantages offered by the selectivity of the biological
      recognition elements and the sensitivity of ECL technique, is a powerful device
      for ultrasensitive biomolecule detection and quantification. Nanomaterials are of
      considerable interest in the biosensor field owing to their unique physical and
      chemical properties, which have led to novel biosensors that have exhibited high
      sensitivity and stability. Nanomaterials including nanoparticles and nanotubes,
      prepared from metals, semiconductor, carbon or polymeric species, have been
      widely investigated for their ability to enhance the efficiencies of ECL
      biosensors, such as taking as modification electrode materials, or as carrier of
      ECL labels and ECL-emitting species. Particularly useful application of
      nanomaterials in ECL biosensors with emphasis on the years 2004-2008 is reviewed.
      Remarks on application of nanomaterials in ECL biosensors are also surveyed.

PMID- 22389625
TI  - The usefulness of the source images of magnetic resonance angiogram in the
      carotid cavernous fistula.

PMID- 22389626
TI  - Emerging measurement techniques for airborne pollutants.

PMID- 22389627
TI  - Movement-related theta rhythm in humans: coordinating self-directed hippocampal
      learning.
AB  - The hippocampus is crucial for episodic or declarative memory and the theta
      rhythm has been implicated in mnemonic processing, but the functional
      contribution of theta to memory remains the subject of intense speculation.
      Recent evidence suggests that the hippocampus might function as a network hub for
      volitional learning. In contrast to human experiments, electrophysiological
      recordings in the hippocampus of behaving rodents are dominated by theta
      oscillations reflecting volitional movement, which has been linked to spatial
      exploration and encoding. This literature makes the surprising cross-species
      prediction that the human hippocampal theta rhythm supports memory by
      coordinating exploratory movements in the service of self-directed learning. We
      examined the links between theta, spatial exploration, and memory encoding by
      designing an interactive human spatial navigation paradigm combined with
      multimodal neuroimaging. We used both non-invasive whole-head
      Magnetoencephalography (MEG) to look at theta oscillations and Functional
      Magnetic Resonance Imaging (fMRI) to look at brain regions associated with
      volitional movement and learning. We found that theta power increases during the
      self-initiation of virtual movement, additionally correlating with subsequent
      memory performance and environmental familiarity. Performance-related hippocampal
      theta increases were observed during a static pre-navigation retrieval phase,
      where planning for subsequent navigation occurred. Furthermore, periods of the
      task showing movement-related theta increases showed decreased fMRI activity in
      the parahippocampus and increased activity in the hippocampus and other brain
      regions that strikingly overlap with the previously observed volitional learning
      network (the reverse pattern was seen for stationary periods). These fMRI changes
      also correlated with participant's performance. Our findings suggest that the
      human hippocampal theta rhythm supports memory by coordinating exploratory
      movements in the service of self-directed learning. These findings directly
      extend the role of the hippocampus in spatial exploration in rodents to human
      memory and self-directed learning.

PMID- 22389628
TI  - p53 regulates cell cycle and microRNAs to promote differentiation of human
      embryonic stem cells.
AB  - Multiple studies show that tumor suppressor p53 is a barrier to
      dedifferentiation; whether this is strictly due to repression of proliferation
      remains a subject of debate. Here, we show that p53 plays an active role in
      promoting differentiation of human embryonic stem cells (hESCs) and opposing self
      renewal by regulation of specific target genes and microRNAs. In contrast to
      mouse embryonic stem cells, p53 in hESCs is maintained at low levels in the
      nucleus, albeit in a deacetylated, inactive state. In response to retinoic acid,
      CBP/p300 acetylates p53 at lysine 373, which leads to dissociation from E3
      ubiquitin ligases HDM2 and TRIM24. Stabilized p53 binds CDKN1A to establish a
      G(1) phase of cell cycle without activation of cell death pathways. In parallel,
      p53 activates expression of miR-34a and miR-145, which in turn repress stem cell
      factors OCT4, KLF4, LIN28A, and SOX2 and prevent backsliding to pluripotency.
      Induction of p53 levels is a key step: RNA-interference-mediated knockdown of p53
      delays differentiation, whereas depletion of negative regulators of p53 or
      ectopic expression of p53 yields spontaneous differentiation of hESCs,
      independently of retinoic acid. Ectopic expression of p53R175H, a mutated form of
      p53 that does not bind DNA or regulate transcription, failed to induce
      differentiation. These studies underscore the importance of a p53-regulated
      network in determining the human stem cell state.

PMID- 22389629
TI  - Induction of biogenic magnetization and redox control by a component of the
      target of rapamycin complex 1 signaling pathway.
AB  - Most organisms are simply diamagnetic, while magnetotactic bacteria and migratory
      animals are among organisms that exploit magnetism. Biogenic magnetization not
      only is of fundamental interest, but also has industrial potential. However, the
      key factor(s) that enable biogenic magnetization in coordination with other
      cellular functions and metabolism remain unknown. To address the requirements for
      induction and the application of synthetic bio-magnetism, we explored the
      creation of magnetism in a simple model organism. Cell magnetization was first
      observed by attraction towards a magnet when normally diamagnetic yeast
      Saccharomyces cerevisiae were grown with ferric citrate. The magnetization was
      further enhanced by genetic modification of iron homeostasis and introduction of
      ferritin. The acquired magnetizable properties enabled the cells to be attracted
      to a magnet, and be trapped by a magnetic column. Superconducting quantum
      interference device (SQUID) magnetometry confirmed and quantitatively
      characterized the acquired paramagnetism. Electron microscopy and energy
      dispersive X-ray spectroscopy showed electron-dense iron-containing aggregates
      within the magnetized cells. Magnetization-based screening of gene knockouts
      identified Tco89p, a component of TORC1 (Target of rapamycin complex 1), as
      important for magnetization; loss of TCO89 and treatment with rapamycin reduced
      magnetization in a TCO89-dependent manner. The TCO89 expression level positively
      correlated with magnetization, enabling inducible magnetization. Several carbon
      metabolism genes were also shown to affect magnetization. Redox mediators
      indicated that TCO89 alters the intracellular redox to an oxidized state in a
      dose-dependent manner. Taken together, we demonstrated that synthetic induction
      of magnetization is possible and that the key factors are local redox control
      through carbon metabolism and iron supply.

PMID- 22389631
TI  - Making magnetic yeast.
AB  - This study demonstrates that normal yeast cells can be magnetized, and identifies
      local redox control via carbon metabolism and iron supply as key factors involved
      in magnetization.

PMID- 22389630
TI  - Host sexual dimorphism and parasite adaptation.
AB  - In species with separate sexes, parasite prevalence and disease expression is
      often different between males and females. This effect has mainly been attributed
      to sex differences in host traits, such as immune response. Here, we make the
      case for how properties of the parasites themselves can also matter.
      Specifically, we suggest that differences between host sexes in many different
      traits, such as morphology and hormone levels, can impose selection on parasites.
      This selection can eventually lead to parasite adaptations specific to the host
      sex more commonly encountered, or to differential expression of parasite traits
      depending on which host sex they find themselves in. Parasites adapted to the sex
      of the host in this way can contribute to differences between males and females
      in disease prevalence and expression. Considering those possibilities can help
      shed light on host-parasite interactions, and impact epidemiological and medical
      science.

PMID- 22389632
TI  - Why does mental health not get the attention it deserves? An application of the
      Shiffman and Smith framework.

PMID- 22389633
TI  - Socioeconomic factors and all cause and cause-specific mortality among older
      people in Latin America, India, and China: a population-based cohort study.
AB  - BACKGROUND: Even in low and middle income countries most deaths occur in older
      adults. In Europe, the effects of better education and home ownership upon
      mortality seem to persist into old age, but these effects may not generalise to
      LMICs. Reliable data on causes and determinants of mortality are lacking. METHODS
      AND FINDINGS: The vital status of 12,373 people aged 65 y and over was determined
      3-5 y after baseline survey in sites in Latin America, India, and China. We
      report crude and standardised mortality rates, standardized mortality ratios
      comparing mortality experience with that in the United States, and estimated
      associations with socioeconomic factors using Cox's proportional hazards
      regression. Cause-specific mortality fractions were estimated using the InterVA
      algorithm. Crude mortality rates varied from 27.3 to 70.0 per 1,000 person-years,
      a 3-fold variation persisting after standardisation for demographic and economic
      factors. Compared with the US, mortality was much higher in urban India and rural
      China, much lower in Peru, Venezuela, and urban Mexico, and similar in other
      sites. Mortality rates were higher among men, and increased with age. Adjusting
      for these effects, it was found that education, occupational attainment, assets,
      and pension receipt were all inversely associated with mortality, and food
      insecurity positively associated. Mutually adjusted, only education remained
      protective (pooled hazard ratio 0.93, 95% CI 0.89-0.98). Most deaths occurred at
      home, but, except in India, most individuals received medical attention during
      their final illness. Chronic diseases were the main causes of death, together
      with tuberculosis and liver disease, with stroke the leading cause in nearly all
      sites. CONCLUSIONS: Education seems to have an important latent effect on
      mortality into late life. However, compositional differences in socioeconomic
      position do not explain differences in mortality between sites. Social protection
      for older people, and the effectiveness of health systems in preventing and
      treating chronic disease, may be as important as economic and human development.

PMID- 22389634
TI  - Association between clean delivery kit use, clean delivery practices, and
      neonatal survival: pooled analysis of data from three sites in South Asia.
AB  - BACKGROUND: Sepsis accounts for up to 15% of an estimated 3.3 million annual
      neonatal deaths globally. We used data collected from the control arms of three
      previously conducted cluster-randomised controlled trials in rural Bangladesh,
      India, and Nepal to examine the association between clean delivery kit use or
      clean delivery practices and neonatal mortality among home births. METHODS AND
      FINDINGS: Hierarchical, logistic regression models were used to explore the
      association between neonatal mortality and clean delivery kit use or clean
      delivery practices in 19,754 home births, controlling for confounders common to
      all study sites. We tested the association between kit use and neonatal mortality
      using a pooled dataset from all three sites and separately for each site. We then
      examined the association between individual clean delivery practices addressed in
      the contents of the kit (boiled blade and thread, plastic sheet, gloves, hand
      washing, and appropriate cord care) and neonatal mortality. Finally, we examined
      the combined association between mortality and four specific clean delivery
      practices (boiled blade and thread, hand washing, and plastic sheet). Using the
      pooled dataset, we found that kit use was associated with a relative reduction in
      neonatal mortality (adjusted odds ratio 0.52, 95% CI 0.39-0.68). While use of a
      clean delivery kit was not always accompanied by clean delivery practices, using
      a plastic sheet during delivery, a boiled blade to cut the cord, a boiled thread
      to tie the cord, and antiseptic to clean the umbilicus were each significantly
      associated with relative reductions in mortality, independently of kit use. Each
      additional clean delivery practice used was associated with a 16% relative
      reduction in neonatal mortality (odds ratio 0.84, 95% CI 0.77-0.92). CONCLUSIONS:
      The appropriate use of a clean delivery kit or clean delivery practices is
      associated with relative reductions in neonatal mortality among home births in
      underserved, rural populations.

PMID- 22389635
TI  - Beyond the numbers: describing care at the end of life.

PMID- 22389636
TI  - Modification of Lipid Bilayer Structure by Diacylglycerol: A Comparative Study of
      Diacylglycerol and Cholesterol.
AB  - Diacylglycerols (DAGs) are important second messengers in biomembranes, and they
      can activate protein kinase C and many other enzymes and receptors. However,
      their interactions with cholesterol and other lipids have not been previously
      studied using molecular dynamics (MD) simulation. In this study, nine independent
      atomistic MD simulations were performed to specifically investigate the
      interactions between di16:0DAG, 16:0,18:1-phosphatidylcholine (POPC), and
      cholesterol. Despite of their substantial differences in chemical structure, DAG
      and cholesterol produce some very similar effects in POPC bilayers: increasing
      acyl chain order and bilayer thickness, reducing volume-per-lipid, and decreasing
      lateral diffusion of molecules. More significantly, DAG also produces a strong
      "condensing effect" in PC bilayers. In comparison, cholesterol is more effective
      than DAG in producing the above effects. The driving force for the condensing
      effect is their molecular shape: DAG and cholesterol both have small polar
      headgroups and large hydrophobic bodies. In a lipid bilayer, in order to avoid
      the unfavorable exposure of their hydrophobic parts to water, neighboring
      phospholipid headgroups move toward cholesterol or DAG to provide cover. Thus,
      seemingly complex interactions between DAG, cholesterol and phospholipid can be
      clearly explained using the Umbrella Model. Our simulations confirmed the
      hypothesis that DAG increases the spacing between phospholipid headgroups, which
      is important for activating protein kinase C and other enzymes. Interestingly,
      our simulations also show that the conventional wisdom that the spacing created
      by a DAG is directly above the DAG molecule is incorrect; instead, the largest
      spacing usually occurs between the first and the second nearest-neighbor PC
      headgroups from a DAG, due to the umbrella effect.

PMID- 22389637
TI  - On Design and Implementation of Neural-Machine Interface for Artificial Legs.
AB  - The quality of life of leg amputees can be improved dramatically by using a cyber
      physical system (CPS) that controls artificial legs based on neural signals
      representing amputees' intended movements. The key to the CPS is the neural
      machine interface (NMI) that senses electromyographic (EMG) signals to make
      control decisions. This paper presents a design and implementation of a novel NMI
      using an embedded computer system to collect neural signals from a physical
      system - a leg amputee, provide adequate computational capability to interpret
      such signals, and make decisions to identify user's intent for prostheses control
      in real time. A new deciphering algorithm, composed of an EMG pattern classifier
      and a post-processing scheme, was developed to identify the user's intended lower
      limb movements. To deal with environmental uncertainty, a trust management
      mechanism was designed to handle unexpected sensor failures and signal
      disturbances. Integrating the neural deciphering algorithm with the trust
      management mechanism resulted in a highly accurate and reliable software system
      for neural control of artificial legs. The software was then embedded in a newly
      designed hardware platform based on an embedded microcontroller and a graphic
      processing unit (GPU) to form a complete NMI for real time testing. Real time
      experiments on a leg amputee subject and an able-bodied subject have been carried
      out to test the control accuracy of the new NMI. Our extensive experiments have
      shown promising results on both subjects, paving the way for clinical feasibility
      of neural controlled artificial legs.

PMID- 22389638
TI  - Impact of HPV Vaccine Availability on Uptake.

PMID- 22389640
TI  - ?
AB  - The necessity of sewers to carry sediment has been recognized for many years.
      Typically, old sewage systems were designated based on self-cleansing concept
      where there is no deposition in sewer. These codes were applicable to non
      cohesive sediments (typically storm sewers). This study presents adaptive neuro
      fuzzy inference system (ANFIS), which is a combination of neural network and
      fuzzy logic, as an alternative approach to predict the functional relationships
      of sediment transport in sewer pipe systems. The proposed relationship can be
      applied to different boundaries with partially full flow. The present ANFIS
      approach gives satisfactory results (r(2) = 0.98 and RMSE = 0.002431) compared to
      the existing predictor.

PMID- 22389639
TI  - Epigenetics Offer New Horizons for Colorectal Cancer Prevention.
AB  - In recent years, colorectal cancer (CRC) incidence has been increasing to become
      a major cause of morbidity and mortality worldwide from cancers, with high rates
      in westernized societies and increasing rates in developing countries. Epigenetic
      modifications including changes in DNA methylation, histone modifications, and
      non-coding RNAs play a critical role in carcinogenesis. Epidemiological data
      suggest that, in comparison to other cancers, these alterations are particularly
      common within the gastrointestinal tract. To explain these observations,
      environmental factors and especially diet were suggested to both prevent and
      induce CRC. Epigenetic alterations are, in contrast to genetic modifications,
      potentially reversible, making the use of dietary agents a promising approach in
      CRC for the development of chemopreventive strategies targeting epigenetic
      mechanisms. This review focuses on CRC-related epigenetic alterations as a
      rationale for various levels of prevention strategies and their potential
      modulation by natural dietary compounds.

PMID- 22389642
TI  - Stable Encapsulation of QD Barcodes with Silica Shells.
AB  - Quantum dot-doped mesoporous microbeads (QDMMs) are encapsulated with silica
      shells for enhanced chemical stability. The results show that a micro-emulsion
      procedure is highly efficient in coating QDMMs with polyvinyl alcohol (PVA),
      which is important in the subsequent deposition of a silica shell. Incorporation
      of fluorescent silane precursors allows direct observation of silica shells by
      fluorescence microscopy. The resulting silica coated QDMMs (QDMM@SiO(2)) exhibit
      remarkable stability against solvent-induced QD leaching and chemical-induced
      fluorescence quenching compared with uncoated QDMMs. Further development of this
      technology such as optimization of silica shell thickness, surface modification
      with non-fouling polymers, and conjugation with biomolecular probes will enable
      clinical translation of the optical barcoding technology for highly multiplexed
      detection and screening of genes and proteins.

PMID- 22389641
TI  - Structural Characterization of Carbohydrates by Fourier Transform Tandem Mass
      Spectrometry.
AB  - Fourier transform tandem mass spectrometry (MS/MS) provides high mass accuracy,
      high sensitivity, and analytical versatility and has therefore emerged as an
      indispensable tool for structural elucidation of biomolecules. Glycosylation is
      one of the most common posttranslational modifications, occurring in ~50% of
      proteins. However, due to the structural diversity of carbohydrates, arising from
      non-template driven biosynthesis, achievement of detailed structural insight is
      highly challenging. This review briefly discusses carbohydrate sample preparation
      and ionization methods, and highlights recent developments in alternative high
      resolution MS/MS strategies, including infrared multiphoton dissociation (IRMPD),
      electron capture dissociation (ECD), and electron detachment dissociation (EDD),
      for carbohydrates with a focus on glycans and proteoglycans from mammalian
      glycoproteins.

PMID- 22389643
TI  - Iron and zinc retention in common beans (Phaseolus vulgaris L.) after home
      cooking.
AB  - BACKGROUND: According to the World Health Organization (WHO), iron, iodine, and
      Vitamin A deficiencies are the most common forms of malnutrition, leading to
      severe public health consequences. The importance of iron and zinc in human
      nutrition and the number of children found to be deficient in these nutrients
      make further studies on retention in cooked grains and cooked bean broth
      important. OBJECTIVES: This work aimed to evaluate iron and zinc retention in six
      common bean (Phaseolus vulgaris L.) cultivars under the following conditions: raw
      beans, regular pot cooking, pressure cooking, with and without previous water
      soaking, and broth. DESIGN: Determination of iron and zinc content in the raw,
      cooked bean grains and broth samples was carried out by Inductively Coupled
      Plasma (ICP) Optical Emission Spectrometry (Spectro Analytical Instrument -
      Spectroflame P). All experiments and analyses were carried out in triplicate.
      RESULTS: Overall, regardless of the cooking method, with or without previous
      water soaking, the highest zinc concentration was found in the cooked bean
      grains. However, pressure cooking and previous water soaking diminished iron
      retention in the cooked grains, while increasing it in the bean broth.
      CONCLUSION: The common bean was confirmed to be an excellent source of iron and
      zinc for human consumption, and it was suggested that beans should be consumed in
      a combined form, i.e. grain with bean broth.

PMID- 22389644
TI  - Public health in action: effective school health needs renewed international
      attention.
AB  - School health programmes as a platform to deliver high-impact health
      interventions are currently underrated by decision makers and do not get adequate
      attention from the international public health community. We describe the award
      winning Fit for School Approach from the Philippines as an example of a large
      scale, integrated, cost-effective and evidence-based programme that bridges the
      gap between sectors, and between evidence and practice. In view of the challenges
      to achieve the health and education related Millennium Development Goals (MDGs)
      in many countries, intensified efforts are required. We present the Fit for
      School Action Framework as a realistic and tested approach that helps to make
      schools places of public health for children and wider communities.

PMID- 22389646
TI  - Total Synthesis of the Aminopropyl Functionalized Ganglioside GM(1).
AB  - GM1 is a common ganglioside pentasaccharide present on mammalian cell surface. It
      has been shown to play important roles in cellular communications and initiation
      of beta-amyloid aggregation. In order to synthesize GM1, an efficient synthetic
      route was developed via a [3+2] strategy. The GM3 trisaccharide acceptor bearing
      an azido propyl group at the reducing end was prepared using the traditional
      acetamide protected sialyl thioglycosyl donor, which gave better
      stereoselectivity than sialyl donors protected with trichloroacetamide or
      oxazolidinone. The glycosylation of the axial 4-hydroxyl group of GM3 by the
      disaccharide donor was found to be highly dependent on donor protective groups.
      Donor bearing the more rigid benzylidene group gave low glycosylation yield.
      Replacing the benzylidene with acetates led to productive coupling and formation
      of the fully protected GM1 pentasaccharide. Deprotection of the pentasaccharide
      produced GM1 functionalized with the amino propyl side chain, which will be a
      valuable probe for biological studies.

PMID- 22389647
TI  - Extreme Heat Resistance of Food Borne Pathogens Campylobacter jejuni, Escherichia
      coli, and Salmonella typhimurium on Chicken Breast Fillet during Cooking.
AB  - The aim of this research was to determine the decimal reduction times of bacteria
      present on chicken fillet in boiling water. The experiments were conducted with
      Campylobacter jejuni, Salmonella, and Escherichia coli. Whole chicken breast
      fillets were inoculated with the pathogens, stored overnight (4 degrees C), and
      subsequently cooked. The surface temperature reached 70 degrees C within 30 sec
      and 85 degrees C within one minute. Extremely high decimal reduction times of
      1.90, 1.97, and 2.20 min were obtained for C. jejuni, E. coli, and S.
      typhimurium, respectively. Chicken meat and refrigerated storage before cooking
      enlarged the heat resistance of the food borne pathogens. Additionally, a high
      challenge temperature or fast heating rate contributed to the level of heat
      resistance. The data were used to assess the probability of illness
      (campylobacteriosis) due to consumption of chicken fillet as a function of
      cooking time. The data revealed that cooking time may be far more critical than
      previously assumed.

PMID- 22389645
TI  - Central control of brown adipose tissue thermogenesis.
AB  - Thermogenesis, the production of heat energy, is an essential component of the
      homeostatic repertoire to maintain body temperature during the challenge of low
      environmental temperature and plays a key role in elevating body temperature
      during the febrile response to infection. Mitochondrial oxidation in brown
      adipose tissue (BAT) is a significant source of neurally regulated metabolic heat
      production in many species from mouse to man. BAT thermogenesis is regulated by
      neural networks in the central nervous system which responds to feedforward
      afferent signals from cutaneous and core body thermoreceptors and to feedback
      signals from brain thermosensitive neurons to activate BAT sympathetic nerve
      activity. This review summarizes the research leading to a model of the
      feedforward reflex pathway through which environmental cold stimulates BAT
      thermogenesis and includes the influence on this thermoregulatory network of the
      pyrogenic mediator, prostaglandin E(2), to increase body temperature during
      fever. The cold thermal afferent circuit from cutaneous thermal receptors,
      through second-order thermosensory neurons in the dorsal horn of the spinal cord
      ascends to activate neurons in the lateral parabrachial nucleus which drive
      GABAergic interneurons in the preoptic area (POA) to inhibit warm-sensitive,
      inhibitory output neurons of the POA. The resulting disinhibition of BAT
      thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT
      sympathetic premotor neurons in the rostral ventromedial medulla, including the
      rostral raphe pallidus, which provide excitatory, and possibly disinhibitory,
      inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently
      recognized central sites influencing BAT thermogenesis and energy expenditure are
      also described.

PMID- 22389650
TI  - Are men from Mars and women from Venus?

PMID- 22389648
TI  - Outsmarting androgen receptor: creative approaches for targeting aberrant
      androgen signaling in advanced prostate cancer.
AB  - Prostatic adenocarcinomas are reliant on androgen receptor (AR) activity for
      survival and progression. Therefore, first-line therapeutic intervention for
      disseminated disease entails the use of AR-directed therapeutics, achieved
      through androgen deprivation and direct AR antagonists. While initially
      effective, recurrent, 'castrate-resistant' prostate cancers arise, for which
      there is no durable means of treatment. An abundance of clinical study and
      preclinical modeling has led to the revelation that restored AR activity is a
      major driver of therapeutic failure and castrate-resistant prostate cancer
      development. The mechanisms underpinning AR reactivation have been identified,
      providing the foundation for a new era of drug discovery and rapid translation
      into the clinic. As will be reviewed in this article, these creative new ways of
      suppressing AR show early promise.

PMID- 22389649
TI  - Genomic features of the human bocaviruses.
AB  - The human bocavirus (HBoV) was initially discovered in 2005 as the second
      pathogenic member of the parvovirus family, next to the human parvovirus B19.
      HBoV has since been shown to be extremely common worldwide and to cause a
      systemic infection in small children often resulting in respiratory disease.
      Three more, presumably enteric, human bocaviruses (HBoV2-4) have been identified
      in stool samples. Parvoviruses are assumed to replicate via their genomic
      terminal hairpin-like structures in a so-called 'rolling-hairpin model'. These
      terminal sequences have recently been partially identified in head-to-tail HBoV
      PCR amplicons from clinical samples, and are most likely hybrid relics of HBoV's
      predecessors, namely bovine parvovirus 1 on the left-hand side and minute virus
      of canines on the right, shown for the first time in this article. Thereby, the
      replication model postulated for HBoV remains questionable as the occurrence of
      head-to-tail sequences is not a typical feature of the rolling-hairpin
      replication model. However, such episomes can also be persistent storage forms of
      the genome.

PMID- 22389651
TI  - Appetite and falls: Old age and lived experiences.
AB  - Falling among older adults is a well-known public health problem but the
      association between falling and appetite is seldom studied although poor
      nutritional status is accepted as a risk factor for falls. On this background the
      aim of this study was to understand how older adults, who have fallen several
      times within a year, related their experiences of appetite as a phenomenon in
      everyday life. In narrative in-depth interviews, eight women and four men
      contributed with their stories. Using interpretative phenomenology the thematic
      analysis resulted in three main themes: appetite for food; appetite for social
      relations and appetite for influence. Eating was not trivial everyday routine and
      required self-regimentation. Meals were not an object of desire, but of
      discipline out of the wish to survive. Feelings, reflections and ambivalence were
      bound to the lack of appetite on food. The participants were oriented towards the
      forbidden, the delicious and to everyday food as a strengthener and as medicine.
      In their dependency on help, home was the framework for establishing social
      relations as means of social support. As well as family and neighbours, the
      significant others were persons on whom the participants were dependent. Personal
      relationships and mutual dependencies may ensure social security in lives
      characterised by contingency and maintain influence in daily life. Falling is
      both a dramatic and a trivial incident where life and death could be at stake.
      From this perspective, connectedness was prominent in all fall stories. The quest
      for influence and a sense of social connectedness was the incentive to re-enter
      local community arenas and to express solidarity. In health-care practice multi
      factorial fall-prevention should be complemented with a multi-dimensional
      approach in order to balance the medical approach with humanistic and societal
      approaches towards fall-prevention.

PMID- 22389652
TI  - Antisocial Personality Disorder in People with Co-Occurring Severe Mental Illness
      and Substance Use Disorders: Clinical, Functional, and Family Relationship
      Correlates.
AB  - Antisocial personality disorder (ASPD) is an important correlate of substance
      abuse severity in the addiction population and in people with co-occurring
      serious mental illness and addiction. Because family members often provide vital
      supports to relatives with co-occurring disorders, this study explored the
      correlates of ASPD in 103 people with co-occurring disorders (79% schizophrenia
      schizoaffective, 21% bipolar disorder) in high contact with relatives
      participating in a family intervention study. Clients with ASPD were more likely
      to have bipolar disorder and to have been married, but less likely to have
      graduated from high school. ASPD was associated with more severe drug abuse and
      depression, worse functioning, and less planning-based social problem solving.
      The relatives of clients with ASPD also reported less planning-based problem
      solving, worse attitudes towards the client, and worse mental health functioning.
      Client ASPD was associated with less long-term exposure to family intervention.
      The findings suggest that clients with ASPD in addition to co-occurring disorders
      are a particularly disadvantaged group with greater illness severity, more
      impaired functioning, and more strained family relationships. These difficulties
      may pose special challenges to delivering family intervention for this group.

PMID- 22389653
TI  - EFFECT OF PARTICLE DIAMETER ON EXCLUSION-ZONE SIZE.
AB  - Particles and solutes are excluded from the vicinity of hydrophilic surfaces,
      leaving large microsphere-free regions known as exclusion zones (EZs). Prior work
      had indicated that EZs could extend to distances of up to several hundred
      micrometers from the nucleating surface. These observations were made on large,
      extended surfaces, leaving open the question whether EZ size might depend on the
      characteristic dimension of the excluding surface. We placed one or few ion
      exchange-resin beads whose diameters varied from 15 MUm to 300 MUm in cuvettes.
      The beads were suffused with aqueous microsphere suspensions for observing the
      surfaces' exclusionary behavior. Results showed a direct relation between bead
      size and EZ size over the full range of bead diameter, implying a similar
      relation for smaller particles or molecules, perhaps extending beyond the
      resolution of the light microscope.

PMID- 22389654
TI  - Traumatic cervical spinal cord injury with "negative" cervical spine CT scan.
AB  - A 46-year-old man fell four steps, striking his neck and having associated neck
      pain and discomfort. He was evaluated at a local emergency department and
      reported no neurological deficit but focal mid cervical tenderness. Radiographs
      and computed tomography (CT) scan were "negative" for cervical spine fracture,
      dislocation or pre-vertebral soft tissue swelling. He was discharged home in a
      cervical collar with a scheduled outpatient follow-up. Over the proceeding hours
      neurologic deterioration occurred, including hand and lower limb weakness with
      the inability to urinate. The patient returned to the local emergency room and
      was transferred to a tertiary care hospital where examination revealed C5ASIAB
      deficits. Repeat high resolution CT scan of the cervical spine with reformatted
      images was unremarkable for osseous fractures except some loss of definition in
      the posterior cervical musculature. Emergency magnetic resonance imaging MRI
      revealed a subluxation of C5/6 right facet (not evident on CT) with disruption of
      the posterior longitudinal ligament, ligamentum flavum, and disc space with
      abnormal T2 weighted spinal cord hyperintense signal at C5/6. He underwent
      emergency C5-C6 anterior and posterior decompression and fusion. One week later
      an examination showed improved C5ASIAD. This case reveals the difficulty of
      assessing the cervical spine for instability and potential limitations of current
      management schemes.

PMID- 22389655
TI  - Profound hyperlipidaemia due to concomitant diabetes and hypothyroidism.
AB  - A previously well 5-year-old girl presented with new onset type 1 diabetes
      mellitus and diabetic ketoacidosis, and was found to be profoundly
      hyperlipidaemic. Further investigations showed that she had associated
      hypothyroidism. She responded to insulin and L-thyroxine treatments and her lipid
      profile returned to normal 2 months after diagnosis. Despite starting
      anticoagulant therapy early, she developed deep vein thrombosis of the lower
      limb. Her family screen did not demonstrate familial hyperlipidaemia or
      hypothyroidism. We discuss our patient's diagnosis and management and highlight
      the challenges faced in this case. A lipid profile may be warranted in cases of
      concomitant diabetes and hypothyroidism to detect this problem and institute
      early treatment(s); monitoring for potential complications is warranted.

PMID- 22389656
TI  - Acute aortic dissection mimics acute inferoposterior wall myocardial infarction
      in a Marfan syndrome patient.
AB  - A 30-year old man with acute chest pain was diagnosed with acute inferoposterior
      wall myocardial infarction following electrocardiography. After a failed coronary
      angiography, an echocardiogram revealed an aortic intimal flap after which acute
      aortic dissection was diagnosed. The patient received a successful Bentall
      operation without immediate complication. Retrospective examination then
      confirmed the diagnosis of Marfan syndrome. This case demonstrates acute aortic
      dissection may mimic acute myocardial infarction.

PMID- 22389657
TI  - Twenty-seven year old man presenting with a strangulated diaphragmatic hernia
      eight years after the initial injury.
AB  - A 27-year-old man presented with a 5 day history of abdominal pain and
      distension, with associated constipation and vomiting. He had presented 8 years
      earlier following a traumatic injury to the left side of the chest, and no
      diaphragmatic injury was reported at that time. On this admission, a computed
      tomography scan showed herniation of the splenic flexure of the colon into the
      left hemithorax. Subsequently, he had an emergency laparotomy for resection, with
      formation of a loop ileostomy. The various imaging techniques all have advantages
      and disadvantages when diagnosing a traumatic diaphragmatic hernia. It is the
      clinician's role to maintain a high index of suspicion when a patient initially
      presents with trauma where a traumatic diaphragmatic hernia may be a possibility.

PMID- 22389658
TI  - Radial head subluxation in an 8-year-old girl with joint hypermobility.
AB  - An 8-year-old girl attended the children's emergency department after having been
      play-fighting with her younger brother. Her arm had been pushed away by her
      father during the fight. The girl immediately complained of pain in her arm and
      refused to move it. Following analgesia and investigation with a plain radiograph
      of the elbow it was decided to attempt a manipulation procedure with the
      possibility that this could represent a 'pulled elbow' in an unusual age group.
      Soon after the manipulation the child was completely pain-free and moving her arm
      fully at the elbow, suggesting a diagnosis of radial head subluxation. The
      patient demonstrated hypermobility of several joints and she was able to
      hyperextend her unaffected elbow by >10 degrees . This case highlights the
      association between radial head subluxation and joint hypermobility.

PMID- 22389659
TI  - Haemoptysis in a patient of achalasia cardia: pulmonary actinomycosis, not
      tuberculosis.
AB  - Actinomycosis is an infectious disease caused by anaerobic gram-positive, non
      spore forming bacteria of the genus Actinomyces that affects the oropharynx,
      digestive tract, and genitalia. Thoracic actinomycosis may affect the respiratory
      tract and the pleura, even extending to the chest wall. Pulmonary actinomycosis
      occurs in immunocompetent persons during the fourth and fifth decades of life,
      with greater prevalence in men, and is generally due to Actinomyces israelii or A
      meyeri. It is frequently misdiagnosed as primary or metastatic lung cancer or
      conventional lung infections (eg, tuberculosis). The accepted predisposing
      factors for bronchopulmonary actinomycosis are poor dental hygiene, alcoholism
      and various chronic debilitating diseases, hiatus hernia, and gastro-oesophageal
      reflux. We report an interesting case of pulmonary actinomycosis presenting with
      haemoptysis, associated with achlasia cardia, and treated as tuberculosis.

PMID- 22389660
TI  - The potential importance of Toll-like receptors in ankylosing spondylitis.
AB  - Cells involved in innate immunity scan for pathogens via extracellular and
      intracellular (endosomal) pattern recognition receptors (PRRs). Engagement of
      PRRs by a specific ligand results in downstream activation of intracellular
      inflammatory cascades. There is emerging evidence indicating that one class of
      PRR, the Toll-like receptor (TLR) plays a potential role in the pathogenesis of
      spondyloarthropathies. Since certain Gram-negative bacteria are known to act as
      triggers for reactive arthritis, there has been much interest in studying the
      role of TLRs in spondyloarthropathies. In this article, we introduce the
      immunology of TLRs followed by a discussion of their potential role in ankylosing
      spondylitis.

PMID- 22389661
TI  - Aptamers for pharmaceuticals and their application in environmental analytics.
AB  - Aptamers are single-stranded DNA or RNA oligonucleotides, which are able to bind
      with high affinity and specificity to their target. This property is used for a
      multitude of applications, for instance as molecular recognition elements in
      biosensors and other assays. Biosensor application of aptamers offers the
      possibility for fast and easy detection of environmental relevant substances.
      Pharmaceutical residues, deriving from human or animal medical treatment, are
      found in surface, ground, and drinking water. At least the whole range of
      frequently administered drugs can be detected in noticeable concentrations.
      Biosensors and assays based on aptamers as specific recognition elements are very
      convenient for this application because aptamer development is possible for toxic
      targets. Commonly used biological receptors for biosensors like enzymes or
      antibodies are mostly unavailable for the detection of pharmaceuticals. This
      review describes the research activities of aptamer and sensor developments for
      pharmaceutical detection, with focus on environmental applications.

PMID- 22389663
TI  - Cross-Cultural Validation of the Inventory of School Motivation (ISM) in the
      Asian Setting: Hong Kong and the Philippines.
AB  - Students' achievement goals in school have received increasing research attention
      because they have been shown to be important in predicting important outcomes. As
      such, there has been a growing interest in measuring and comparing them across
      different cultural groups. However, these comparisons cannot be made until
      validity evidence has been attained to support the use of an instrument in the
      new cultural setting. In this study, we investigated the cross-cultural
      applicability of the Inventory of School Motivation (ISM, McInerney et al.
      American Educational Research Journal 34:207-236, 1997) in the Hong Kong Chinese
      and Philippine contexts using both within-network and between-network approaches
      to construct validation. The ISM measures four types of achievement goals:
      mastery, performance, social, and extrinsic goals. 1,406 high school students
      from Hong Kong (n = 697) and the Philippines (n = 709) participated. Results of
      the within-network test showed that the ISM had good internal consistency
      reliability and the confirmatory factor analysis provided support for the
      hypothesized four-factor model. Multigroup confirmatory factor analyses supported
      invariance of factor loadings across the two samples. The between-network test
      also indicated that these achievement goals correlated systematically with
      different aspects of students' self-concepts. These findings support the
      applicability of the ISM among Hong Kong Chinese and Filipino students.

PMID- 22389662
TI  - A Step-up Approach for Cell Therapy in Stroke: Translational Hurdles of Bone
      Marrow-Derived Stem Cells.
AB  - Stroke remains a significant unmet condition in the USA and throughout the world.
      To date, only approximately 3% of the population suffering an ischemic stroke
      benefit from the thrombolytic drug tissue plasminogen activator, largely due to
      the drug's narrow therapeutic window. The last decade has witnessed extensive
      laboratory studies suggesting the therapeutic potential of cell-based therapy for
      stroke. Limited clinical trials of cell therapy in stroke patients are currently
      being pursued. Bone marrow-derived stem cells are an attractive, novel
      transplantable cell source for stroke. There remain many unanswered questions in
      the laboratory before cell therapy can be optimized for transplantation in the
      clinical setting. Here, we discuss the various translational hurdles encountered
      in bringing cell therapy from the laboratory to the clinic, using stem cell
      therapeutics as an emerging paradigm for stroke as a guiding principle. In
      particular, we focus on the preclinical studies of cell transplantation in
      experimental stroke with emphasis on a better understanding of mechanisms of
      action in an effort to optimize efficacy and to build a safety profile for
      advancing cell therapy to the clinic. A forward looking strategy of combination
      therapy involving stem cell transplantation and pharmacologic treatment is also
      discussed. 

PMID- 22389664
TI  - Prenatal detection of aneuploidy and imbalanced chromosomal arrangements by
      massively parallel sequencing.
AB  - Fetal chromosomal abnormalities are the most common reasons for invasive prenatal
      testing. Currently, G-band karyotyping and several molecular genetic methods have
      been established for diagnosis of chromosomal abnormalities. Although these
      testing methods are highly reliable, the major limitation remains restricted
      resolutions or can only achieve limited coverage on the human genome at one time.
      The massively parallel sequencing (MPS) technologies which can reach single base
      pair resolution allows detection of genome-wide intragenic deletions and
      duplication challenging karyotyping and microarrays as the tool for prenatal
      diagnosis. Here we reported a novel and robust MPS-based method to detect
      aneuploidy and imbalanced chromosomal arrangements in amniotic fluid (AF)
      samples. We sequenced 62 AF samples on Illumina GAIIx platform and with averagely
      0.01* whole genome sequencing data we detected 13 samples with numerical
      chromosomal abnormalities by z-test. With up to 2* whole genome sequencing data
      we were able to detect microdeletion/microduplication (ranged from 1.4 Mb to 37.3
      Mb of 5 samples from chorionic villus sampling (CVS) using SeqSeq algorithm. Our
      work demonstrated MPS is a robust and accurate approach to detect aneuploidy and
      imbalanced chromosomal arrangements in prenatal samples.

PMID- 22389667
TI  - A new ant species of the genus Tetramorium mayr, 1855 (Hymenoptera: Formicidae)
      from Saudi Arabia, with a revised key to the Arabian species.
AB  - Tetramorium amalae sp. n. is described and illustrated from Saudi Arabia based on
      two worker caste specimens collected in Al Bahah region. The new species belongs
      to the T. shilohense group and appears to be closely related to T. dysderke
      Bolton from Nigeria. T. amalae is distinguished by having well-developed frontal
      carinae, smaller eyes, greater head length and width, greater pronotal width, and
      the petiole node is longer than broad. Tetramorium latinode Collingwood & Agosti
      is recorded for the first time from Saudi Arabia and for only the second time
      since the original description. The worker caste of T. latinode is redescribed
      and illustrated using scanning electron micrographs to facilitate recognition and
      the gyne is described for the first time with observations given on species
      relationships, biology and habitat. A revised key to the nineteen Tetramorium
      species recorded from Arabian Peninsula based on worker castes is provided.
      Tetramorium bicarinatum (Nylander) is recorded for the first time from Saudi
      Arabia. It is suggested that T. amalae and T. latinode are endemic to the Arabian
      Peninsula.

PMID- 22389665
TI  - Mesenchymal transition and PDGFRA amplification/mutation are key distinct
      oncogenic events in pediatric diffuse intrinsic pontine gliomas.
AB  - Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant
      pediatric brain tumor and its prognosis is universaly fatal. No significant
      improvement has been made in last thirty years over the standard treatment with
      radiotherapy. To address the paucity of understanding of DIPGs, we have carried
      out integrated molecular profiling of a large series of samples obtained with
      stereotactic biopsy at diagnosis. While chromosomal imbalances did not
      distinguish DIPG and supratentorial tumors on CGHarrays, gene expression
      profiling revealed clear differences between them, with brainstem gliomas
      resembling midline/thalamic tumours, indicating a closely-related origin. Two
      distinct subgroups of DIPG were identified. The first subgroup displayed
      mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment
      consistent with the possibility to grow tumor stem cells from these biopsies. The
      other subgroup displayed oligodendroglial features, and appeared largely driven
      by PDGFRA, in particular through amplification and/or novel missense mutations in
      the extracellular domain. Patients in this later group had a significantly worse
      outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold
      greater that the ones in the other subgroup (p = 0.041, Cox regression model).
      The worse outcome of patients with the oligodendroglial type of tumors was
      confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median
      OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct
      transcriptional subclasses of DIPG with specific genomic alterations can be
      defined at diagnosis by oligodendroglial differentiation or mesenchymal
      transition, respectively. Classifying these tumors by signal transduction pathway
      activation and by mutation in pathway member genes may be particularily valuable
      for the development of targeted therapies.

PMID- 22389666
TI  - Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients
      with hearing impairment.
AB  - BACKGROUND: Thirty thousand infants are born every year with congenital hearing
      impairment in mainland China. Racial and regional factors are important in
      clinical diagnosis of genetic deafness. However, molecular etiology of hearing
      impairment in the Tibetan Chinese population living in the Tibetan Plateau has
      not been investigated. To provide appropriate genetic testing and counseling to
      Tibetan families, we investigated molecular etiology of nonsyndromic deafness in
      this population. METHODS: A total of 114 unrelated deaf Tibetan children from the
      Tibet Autonomous Region were enrolled. Five prominent deafness-related genes,
      GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear
      development was evaluated by temporal CT. A total of 106 Tibetan hearing normal
      individuals were included as genetic controls. For radiological comparison, 120
      patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed
      by temporal CT. RESULTS: None of the Tibetan patients carried diallelic GJB2 or
      SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried
      homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S
      rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear
      malformation was made in 20.18% of the Tibetan patients and 21.67% of the Han
      deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity,
      was not found in theTibetan patients, but was seen in 18.33% of the Han patients.
      Common molecular etiologies, GJB2 and SLC26A4 mutations, were rare in the Tibetan
      Chinese deaf population. CONCLUSION: The mutation spectrum of hearing loss
      differs significantly between Chinese Tibetan patients and Han patients. The
      incidence of inner ear malformation in Tibetans is almost as high as that in Han
      deaf patients, but the types of malformation vary greatly. Hypoxia and special
      environment in plateau may be one cause of developmental inner ear deformity in
      this population.

PMID- 22389668
TI  - CT image segmentation using FEM with optimized boundary condition.
AB  - The authors propose a CT image segmentation method using structural analysis that
      is useful for objects with structural dynamic characteristics. Motivation of our
      research is from the area of genetic activity. In order to reveal the roles of
      genes, it is necessary to create mutant mice and measure differences among them
      by scanning their skeletons with an X-ray CT scanner. The CT image needs to be
      manually segmented into pieces of the bones. It is a very time consuming to
      manually segment many mutant mouse models in order to reveal the roles of genes.
      It is desirable to make this segmentation procedure automatic. Although numerous
      papers in the past have proposed segmentation techniques, no general segmentation
      method for skeletons of living creatures has been established. Against this
      background, the authors propose a segmentation method based on the concept of
      destruction analogy. To realize this concept, structural analysis is performed
      using the finite element method (FEM), as structurally weak areas can be expected
      to break under conditions of stress. The contribution of the method is its
      novelty, as no studies have so far used structural analysis for image
      segmentation. The method's implementation involves three steps. First, finite
      elements are created directly from the pixels of a CT image, and then candidates
      are also selected in areas where segmentation is thought to be appropriate. The
      second step involves destruction analogy to find a single candidate with high
      strain chosen as the segmentation target. The boundary conditions for FEM are
      also set automatically. Then, destruction analogy is implemented by replacing
      pixels with high strain as background ones, and this process is iterated until
      object is decomposed into two parts. Here, CT image segmentation is demonstrated
      using various types of CT imagery.

PMID- 22389669
TI  - From retinal waves to activity-dependent retinogeniculate map development.
AB  - A neural model is described of how spontaneous retinal waves are formed in infant
      mammals, and how these waves organize activity-dependent development of a
      topographic map in the lateral geniculate nucleus, with connections from each eye
      segregated into separate anatomical layers. The model simulates the spontaneous
      behavior of starburst amacrine cells and retinal ganglion cells during the
      production of retinal waves during the first few weeks of mammalian postnatal
      development. It proposes how excitatory and inhibitory mechanisms within
      individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and
      signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by
      controlling the after-hyperpolarization currents of starburst amacrine cells.
      Given the critical role of the geniculate map in the development of visual
      cortex, these results provide a foundation for analyzing the temporal dynamics
      whereby the visual cortex itself develops.

PMID- 22389670
TI  - Inhibition of TACE activity enhances the susceptibility of myeloma cells to
      TRAIL.
AB  - BACKGROUND: TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L)
      selectively induces apoptosis in various cancer cells including myeloma (MM)
      cells. However, the susceptibility of MM cells to TRAIL is largely low in most of
      MM cells by yet largely unknown mechanisms. Because TNF-alpha converting enzyme
      (TACE) can cleave some TNF receptor family members, in the present study we
      explored the roles of proteolytic modulation by TACE in TRAIL receptor expression
      and TRAIL-mediated cytotoxicity in MM cells. METHODOLOGY/PRINCIPAL FINDINGS: MM
      cells preferentially expressed death receptor 4 (DR4) but not DR5 on their
      surface along with TACE. Conditioned media from RPMI8226 and U266 cells contained
      a soluble form of DR4. The DR4 levels in these conditioned media were reduced by
      TACE inhibition by the TACE inhibitor TAPI-0 as well as TACE siRNA. Conversely,
      the TACE inhibition restored surface levels of DR4 but not DR5 in these cells
      without affecting DR4 mRNA levels. The TACE inhibition was able to restore cell
      surface DR4 expression in MM cells even in the presence of bone marrow stromal
      cells or osteoclasts, and enhanced the cytotoxic effects of recombinant TRAIL and
      an agonistic antibody against DR4 on MM cells. CONCLUSIONS/SIGNIFICANCE: These
      results demonstrate that MM cells post-translationally down-modulate the cell
      surface expression of DR4 through ectodomain shedding by endogenous TACE, and
      that TACE inhibition is able to restore cell surface DR4 levels and the
      susceptibility of MM cells to TRAIL or an agonistic antibody against DR4. Thus,
      TACE may protect MM cells from TRAIL-mediated death through down-modulation of
      cell-surface DR4. It can be envisaged that TACE inhibition augments clinical
      efficacy of TRAIL-based immunotherapy against MM, which eventually becomes
      resistant to the present therapeutic modalities.

PMID- 22389671
TI  - Involuntary monitoring of sound signals in noise is reflected in the human
      auditory evoked N1m response.
AB  - Constant sound sequencing as operationalized by repeated stimulation with tones
      of the same frequency has multiple effects. On the one hand, it activates
      mechanisms of habituation and refractoriness, which are reflected in the decrease
      of response amplitude of evoked responses. On the other hand, the constant
      sequencing acts as spectral cueing, resulting in tones being detected faster and
      more accurately. With the present study, by means of magnetoencephalography, we
      investigated the impact of repeated tone stimulation on the N1m auditory evoked
      fields, while listeners were distracted from the test sounds. We stimulated
      subjects with trains of either four tones of the same frequency, or with trains
      of randomly assigned frequencies. The trains were presented either in a silent or
      in a noisy background. In silence, the patterns of source strength decline
      originating from repeated stimulation suggested both, refractoriness as well as
      habituation as underlying mechanisms. In noise, in contrast, there was no
      indication of source strength decline. Furthermore, we found facilitating effects
      of constant sequencing regarding the detection of the single tones as indexed by
      a shortening of N1m latency. We interpret our findings as a correlate of a bottom
      up mechanism that is constantly monitoring the incoming auditory information,
      even when voluntary attention is directed to a different modality.

PMID- 22389672
TI  - A garlic derivative, S-allylcysteine (SAC), suppresses proliferation and
      metastasis of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant and metastatic.
      Currently, there is no effective chemotherapy for patients with advanced HCC
      leading to an urgent need to seek for novel therapeutic options. We aimed to
      investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the
      proliferation and metastasis of HCC. METHODOLOGY/PRINCIPAL FINDINGS: A series of
      in vitro experiments including MTT, colony-forming, wound-healing, invasion,
      apoptosis and cell cycle assays were performed to examine the anti-proliferative
      and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The
      therapeutic values of SAC single and combined with cisplatin treatments were
      examined in an in vivo orthotopic xenograft liver tumor model. The result showed
      that the proliferation rate and colony-forming abilities of MHCC97L cells were
      suppressed by SAC together with significant suppression of the expressions of
      proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA).
      Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding
      with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC
      significantly induced apoptosis and necrosis of MHCC97L cells through suppressing
      Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC
      could significantly induce the S phase arrest of MHCC97L cells together with down
      regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model
      demonstrated that SAC single or combined with cisplatin treatment inhibited the
      progression and metastasis of HCC tumor. CONCLUSIONS/SIGNIFICANCE: Our data
      demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC
      cells and suggest that SAC may be a potential therapeutic agent for the treatment
      of HCC patients.

PMID- 22389673
TI  - Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and
      sustained susceptibility to multiple death receptor signaling pathways.
AB  - BACKGROUND: Death receptors (DR) of the TNF family function as anti-tumor immune
      effector molecules. Tumor cells, however, often exhibit DR-signaling resistance.
      Previous studies indicate that radiation can modify gene expression within tumor
      cells and increase tumor cell sensitivity to immune attack. The aim of this study
      is to investigate the synergistic effect of sub-lethal doses of ionizing
      radiation in sensitizing colorectal carcinoma cells to death receptor-mediated
      apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate
      the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5,
      TNF-R1 and LTbetaR) was examined in colorectal tumor cells. The functional
      significance of sub-lethal doses of radiation in enhancing tumor cell
      susceptibility to DR-induced apoptosis was determined by in vitro functional
      sensitivity assays. The longevity of these changes and the underlying molecular
      mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to
      death receptor-mediated apoptosis were also examined. We found that radiation
      increased surface expression of Fas, DR4 and DR5 but not LTbetaR or TNF-R1 in
      these cells. Increased expression of DRs was observed 2 days post-irradiation and
      remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation
      alone exhibited minimal cell death, but effectively sensitized three of three
      colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not
      LTbetaR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell
      death lasted as long as 5-days post-irradiation. Specific analysis of
      intracellular sensitizers to apoptosis indicated that while radiation did reduce
      Bcl-X(L) and c-FLIP protein expression, this reduction did not correlate with the
      radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the
      three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can
      overcome Fas and TRAIL resistance that is long lasting. Overall, results of these
      investigations suggest that non-lethal doses of radiation can be used to make
      human tumors more amenable to attack by anti-tumor effector molecules and cells.

PMID- 22389674
TI  - An updated review of the efficacy of cupping therapy.
AB  - BACKGROUND: Since 1950, traditional Chinese medicine (TCM) cupping therapy has
      been applied as a formal modality in hospitals throughout China and elsewhere in
      the world. Based on a previous systematic literature review of clinical studies
      on cupping therapy, this study presents a thorough review of randomized
      controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy.
      METHOD: Six databases were searched for articles published through 2010. RCTs on
      cupping therapy for various diseases were included. Studies on cupping therapy
      combined with other TCM treatments versus non-TCM therapies were excluded.
      RESULTS: 135 RCTs published from 1992 through 2010 were identified. The studies
      were generally of low methodological quality. Diseases for which cupping therapy
      was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and
      dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was
      used in most trials, followed by retained cupping, moving cupping, and flash
      cupping. Meta-analysis showed cupping therapy combined with other TCM treatments
      was significantly superior to other treatments alone in increasing the number of
      cured patients with herpes zoster, facial paralysis, acne, and cervical
      spondylosis. No serious adverse effects were reported in the trials. CONCLUSIONS:
      Numerous RCTs on cupping therapy have been conducted and published during the
      past decades. This review showed that cupping has potential effect in the
      treatment of herpes zoster and other specific conditions. However, further
      rigorously designed trials on its use for other conditions are warranted.

PMID- 22389675
TI  - Insights into the complex associations between MHC class II DRB polymorphism and
      multiple gastrointestinal parasite infestations in the striped mouse.
AB  - Differences in host susceptibility to different parasite types are largely based
      on the degree of matching between immune genes and parasite antigens.
      Specifically the variable genes of the major histocompatibility complex (MHC)
      play a major role in the defence of parasites. However, underlying genetic
      mechanisms in wild populations are still not well understood because there is a
      lack of studies which deal with multiple parasite infections and their
      competition within. To gain insights into these complex associations, we
      implemented the full record of gastrointestinal nematodes from 439 genotyped
      individuals of the striped mouse, Rhabdomys pumilio. We used two different
      multivariate approaches to test for associations between MHC class II DRB
      genotype and multiple nematodes with regard to the main pathogen-driven selection
      hypotheses maintaining MHC diversity and parasite species-specific co
      evolutionary effects. The former includes investigations of a 'heterozygote
      advantage', or its specific form a 'divergent-allele advantage' caused by highly
      dissimilar alleles as well as possible effects of specific MHC-alleles selected
      by a 'rare allele advantage' (= negative 'frequency-dependent selection'). A
      combination of generalized linear mixed models (GLMMs) and co-inertia (COIA)
      analyses made it possible to consider multiple parasite species despite the risk
      of type I errors on the population and on the individual level. We could not find
      any evidence for a 'heterozygote' advantage but support for 'divergent-allele'
      advantage and infection intensity. In addition, both approaches demonstrated high
      concordance of positive as well as negative associations between specific MHC
      alleles and certain parasite species. Furthermore, certain MHC alleles were
      associated with more than one parasite species, suggesting a many-to-many gene
      parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a
      pleiotropic effect, involving three nematode species. Our study demonstrates the
      co-existence of specialist and generalist MHC alleles in terms of parasite
      detection which may be an important feature in the maintenance of MHC
      polymorphism.

PMID- 22389676
TI  - Transgenerational actions of environmental compounds on reproductive disease and
      identification of epigenetic biomarkers of ancestral exposures.
AB  - Environmental factors during fetal development can induce a permanent epigenetic
      change in the germ line (sperm) that then transmits epigenetic transgenerational
      inheritance of adult-onset disease in the absence of any subsequent exposure. The
      epigenetic transgenerational actions of various environmental compounds and
      relevant mixtures were investigated with the use of a pesticide mixture
      (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and
      phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After
      transient exposure of F0 gestating female rats during the period of embryonic
      gonadal sex determination, the subsequent F1-F3 generations were obtained in the
      absence of any environmental exposure. The effects on the F1, F2 and F3
      generations pubertal onset and gonadal function were assessed. The plastics,
      dioxin and jet fuel were found to promote early-onset female puberty
      transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected
      transgenerationally. Ovarian primordial follicle pool size was significantly
      decreased with all treatments transgenerationally. Differential DNA methylation
      of the F3 generation sperm promoter epigenome was examined. Differential DNA
      methylation regions (DMR) were identified in the sperm of all exposure lineage
      males and found to be consistent within a specific exposure lineage, but
      different between the exposures. Several genomic features of the DMR, such as low
      density CpG content, were identified. Exposure-specific epigenetic biomarkers
      were identified that may allow for the assessment of ancestral environmental
      exposures associated with adult onset disease.

PMID- 22389678
TI  - Chemical composition and antioxidant activities of Broussonetia papyrifera
      fruits.
AB  - Fruits of Broussonetia papyrifera from South China were analyzed for their total
      chemical composition, and antioxidant activities in ethanol and aqueous extracts.
      In the fruit of this plant, the crude protein, crude fat and carbohydrates was
      7.08%, 3.72% and 64.73% of dry weight, respectively. The crude protein, crude fat
      and carbohydrates were 15.71%, 20.51% and 36.09% of dry weight, respectively.
      Fatty acid and amino acid composition of the fruit were analyzed. Unsaturated
      fatty acid concentration was 70.6% of the total fatty acids. The percentage of
      the essential amino acids (EAAs) was 40.60% of the total amino acids.
      Furthermore, B. papyrifera fruit are rich in many mineral elements and vitamins.
      Total phenolic content was assessed using the Folin-Ciocalteau assay, whereas
      antioxidant activities were assessed by measuring the ability of the two extracts
      to scavenge DPPH radicals, inhibit peroxidation, and chelate ferric ions. Their
      reducing power was also assessed. Results indicated that the aqueous extract of
      B. papyrifera was a more potent reducing agent and radical-scavenger than the
      ethanol extract. GC-MS analysis of the ethanol extract showed the presence of
      some acid-containing compounds. The changes in total phenolic content and
      antioxidant capacity in B. papyrifera from four different regions grown under
      normal conditions were assessed. The antioxidant activity of different extracts
      was positively associated with their total phenolic content. These results
      suggest that the fruit of B. papyrifera could be used in dietary supplement
      preparations, or as a food additive, for nutritional gain, or to prevent
      oxidation in food products.

PMID- 22389677
TI  - HIV-neutralizing activity of cationic polypeptides in cervicovaginal secretions
      of women in HIV-serodiscordant relationships.
AB  - BACKGROUND: HIV exposed seronegative (HESN) women represent the population most
      in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can
      potentially be regulated for this purpose and we here aimed to determine their
      endogenous expression and HIV neutralizing activity in genital secretions of
      women at risk of HIV infection. METHODOLOGY/PRINCIPAL FINDINGS: Cervicovaginal
      secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n =
      164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for
      the cationic polypeptides HNP1-3, LL-37 and SLPI by ELISA and for HIV
      neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median
      levels of HNP1-3 and LL-37 in CVS were similar across study groups. Neither HSV-2
      serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1-3
      or LL-37 in the HESN women. However, an association with their partner's viral
      load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated
      with higher levels of HNP1-3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI
      was most abundant in the low-risk group and did not correlate with male partner's
      viral load in the HESN women. HIV neutralizing activity was found in CVS of all
      study groups. In experimental studies, selective depletion of cationic
      polypeptides from CVS rendered the remaining CVS fraction non-neutralizing,
      whereas the cationic polypeptide fraction retained the activity. Furthermore,
      recombinant HNP1-3 and LL-37 could induce neutralizing activity when added to CVS
      lacking intrinsic activity. CONCLUSIONS/SIGNIFICANCE: These findings show that
      CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing
      activity. Although several innate immune proteins, including HNP1-3 and LL-37,
      contribute to this activity these molecules can also have inflammatory
      properties. This balance is influenced by hormonal and environmental factors and
      in the present HIV serodiscordant couple cohort study we show that a partner's
      viral load is associated with levels of such molecules.

PMID- 22389679
TI  - Adaptive response in mice exposed to 900 MHz radiofrequency fields: primary DNA
      damage.
AB  - The phenomenon of adaptive response (AR) in animal and human cells exposed to
      ionizing radiation is well documented in scientific literature. We have examined
      whether such AR could be induced in mice exposed to non-ionizing radiofrequency
      fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF
      at 120 uW/cm(2) power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then
      subjected to an acute dose of 3 Gy gamma-radiation. The primary DNA damage in the
      form of alkali labile base damage and single strand breaks in the DNA of
      peripheral blood leukocytes was determined using the alkaline comet assay. The
      results indicated that the extent of damage in mice which were pre-exposed to RF
      for 1 day and then subjected to gamma-radiation was similar and not significantly
      different from those exposed to gamma-radiation alone. However, mice which were
      pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage
      and was significantly different from those exposed to gamma-radiation alone.
      Thus, the data indicated that RF pre-exposure is capable of inducing AR and
      suggested that the pre-exposure for more than 4 hours for 1 day is necessary to
      elicit such AR.

PMID- 22389680
TI  - Exocyst subunits Exo70 and Exo84 cooperate with small GTPases to regulate
      behavior and endocytic trafficking in C. elegans.
AB  - The exocyst complex is required for cell polarity regulation and the targeting
      and tethering of transport vesicles to the plasma membrane. The complex is
      structurally well conserved, however, the functions of individual subunits and
      their regulation is poorly understood. Here we characterize the mutant phenotypes
      for the exocyst complex genes exoc-7 (exo70) and exoc-8 (exo84) in Caenorhabditis
      elegans. The mutants display pleiotropic behavior defects that resemble those
      observed in cilia mutants (slow growth, uncoordinated movement, defects in chemo
      , mechano- and thermosensation). However, no obvious morphological defects in
      cilia were observed. A targeted RNAi screen for small GTPases identified eleven
      genes with enhanced phenotypes when combined with exoc-7, exoc-8 single and exoc
      7;exoc-8 double mutants. The screen verified previously identified functional
      links between the exocyst complex and small GTPases and, in addition, identified
      several novel potential regulators of exocyst function. The exoc-8 and exoc
      7;exoc-8 mutations caused a significant size increase in the rab-10 RNAi-induced
      endocytic vacuoles in the intestinal epithelial cells. In addition, exoc-8 and
      exoc-7;exoc-8 mutations resulted in up-regulation of RAB-10 expression and
      affected the accumulation of endocytic marker proteins in these cells in response
      to rab-10 RNAi. The findings identify novel, potential regulators for exocyst
      function and show that exoc-7 and exoc-8 are functionally linked to rab-10 in
      endosomal trafficking in intestinal epithelial cells in C. elegans.

PMID- 22389681
TI  - Batrachochytrium dendrobatidis shows high genetic diversity and ecological niche
      specificity among haplotypes in the Maya Mountains of Belize.
AB  - The amphibian pathogen Batrachochytrium dendrobatidis (Bd) has been implicated in
      amphibian declines around the globe. Although it has been found in most countries
      in Central America, its presence has never been assessed in Belize. We set out to
      determine the range, prevalence, and diversity of Bd using quantitative PCR
      (qPCR) and sequencing of a portion of the 5.8 s and ITS1-2 regions. Swabs were
      collected from 524 amphibians of at least 26 species in the protected areas of
      the Maya Mountains of Belize. We sequenced a subset of 72 samples that had tested
      positive for Bd by qPCR at least once; 30 samples were verified as Bd. Eight
      unique Bd haplotypes were identified in the Maya Mountains, five of which were
      previously undescribed. We identified unique ecological niches for the two most
      broadly distributed haplotypes. Combined with data showing differing virulence
      shown in different strains in other studies, the 5.8 s - ITS1-2 region diversity
      found in this study suggests that there may be substantial differences among
      populations or haplotypes. Future work should focus on whether specific
      haplotypes for other genomic regions and possibly pathogenicity can be associated
      with haplotypes at this locus, as well as the integration of molecular tools with
      other ecological tools to elucidate the ecology and pathogenicity of Bd.

PMID- 22389682
TI  - Impairment of vowel articulation as a possible marker of disease progression in
      Parkinson's disease.
AB  - PURPOSE: The aim of the current study was to survey if vowel articulation in
      speakers with Parkinson's disease (PD) shows specific changes in the course of
      the disease. METHOD: 67 patients with PD (42 male) and 40 healthy speakers (20
      male) were tested and retested after an average time interval of 34 months.
      Participants had to read a given text as source for subsequent calculation of the
      triangular vowel space area (tVSA) and vowel articulation index (VAI).
      Measurement of tVSA and VAI were based upon analysis of the first and second
      formant of the vowels /alpha/, /i/and /u/ extracted from defined words within the
      text. RESULTS: At first visit, VAI values were reduced in male and female PD
      patients as compared to the control group, and showed a further decrease at the
      second visit. Only in female Parkinsonian speakers, VAI was correlated to overall
      speech impairment based upon perceptual impression. VAI and tVSA were correlated
      to gait impairment, but no correlations were seen between VAI and global motor
      impairment or overall disease duration. tVSA showed a similar reduction in the PD
      as compared to the control group and was also found to further decline between
      first and second examination in female, but not in male speakers with PD.
      CONCLUSIONS: Measurement of VAI seems to be superior to tVSA in the description
      of impaired vowel articulation and its further decline in the course of the
      disease in PD. Since impairment of vowel articulation was found to be independent
      from global motor function but correlated to gait dysfunction, measurement of
      vowel articulation might have a potential to serve as a marker of axial disease
      progression.

PMID- 22389683
TI  - Crystal structure of the minimalist Max-E47 protein chimera.
AB  - Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic
      region of Max and the dimerization region of E47, both members of the basic
      region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native
      Max, Max-E47 binds with high affinity and specificity to the E-box site, 5'
      CACGTG, both in vivo and in vitro. We have determined the crystal structure of
      Max-E47 at 1.7 A resolution, and found that it associates to form a well
      structured dimer even in the absence of its cognate DNA. Analytical
      ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar
      concentrations, indicating that the Max-E47 dimer is stable in the absence of
      DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the
      E-box site induce similar levels of helical secondary structure in Max-E47. These
      results suggest that Max-E47 may bind to the E-box following the two-step
      mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where
      protein binds to DNA without sequence specificity is followed by a slow step
      where specific protein:DNA interactions are fine-tuned, leading to sequence
      specific recognition. Collectively, these results show that the designed Max-E47
      protein chimera behaves both structurally and functionally like its native
      counterparts.

PMID- 22389684
TI  - Intra- and inter-subunit disulfide bond formation is nonessential in adeno
      associated viral capsids.
AB  - The capsid proteins of adeno-associated viruses (AAV) have five conserved
      cysteine residues. Structural analysis of AAV serotype 2 reveals that Cys289 and
      Cys361 are located adjacent to each other within each monomer, while Cys230 and
      Cys394 are located on opposite edges of each subunit and juxtaposed at the
      pentamer interface. The Cys482 residue is located at the base of a surface loop
      within the trimer region. Although plausible based on molecular dynamics
      simulations, intra- or inter-subunit disulfides have not been observed in
      structural studies. In the current study, we generated a panel of Cys-to-Ser
      mutants to interrogate the potential for disulfide bond formation in AAV capsids.
      The C289S, C361S and C482S mutants were similar to wild type AAV with regard to
      titer and transduction efficiency. However, AAV capsid protein subunits with
      C230S or C394S mutations were prone to proteasomal degradation within the host
      cells. Proteasomal inhibition partially blocked degradation of mutant capsid
      proteins, but failed to rescue infectious virions. While these results suggest
      that the Cys230/394 pair is critical, a C394V mutant was found viable, but not
      the corresponding C230V mutant. Although the exact nature of the structural
      contribution(s) of Cys230 and Cys394 residues to AAV capsid formation remains to
      be determined, these results support the notion that disulfide bond formation
      within the Cys289/361 or Cys230/394 pair appears to be nonessential. These
      studies represent an important step towards understanding the role of inter
      subunit interactions that drive AAV capsid assembly.

PMID- 22389685
TI  - Etiology and clinical characterization of respiratory virus infections in adult
      patients attending an emergency department in Beijing.
AB  - BACKGROUND: Acute respiratory tract infections (ARTIs) represent a serious global
      health burden. To date, few reports have addressed the prevalence of respiratory
      viruses (RVs) in adults with ARTIs attending an emergency department (ED).
      Therefore, the potential impact of respiratory virus infections on such patients
      remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine the epidemiological
      and clinical profiles of common and recently discovered respiratory viruses in
      adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was
      conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416
      ARTI patients were checked for 13 respiratory viruses using multiple reverse
      transcription polymerase chain reaction(RT-PCR) assays for common respiratory
      viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs),
      picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses
      (PIVs) 1-3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and
      human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were
      detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients
      tested positive for more than one virus. PICs (17.79%) were the dominant agents
      detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV,
      PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and
      the dominant virus infections detected differed significantly between ours and a
      previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC
      (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns
      of clinical symptoms were associated with different respiratory viruses.
      CONCLUSIONS: The pattern of RV involvement in adults with ARTIs attending an ED
      in China differs from that previously reported. The high prevalence of viruses
      (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the
      development of safe and effective therapeutic approaches for these viruses.

PMID- 22389686
TI  - Structural analysis of the C-terminal region (modules 18-20) of complement
      regulator factor H (FH).
AB  - Factor H (FH) is a soluble regulator of the human complement system affording
      protection to host tissues. It selectively inhibits amplification of C3b, the
      activation-specific fragment of the abundant complement component C3, in fluid
      phase and on self-surfaces and accelerates the decay of the alternative pathway
      C3 convertase, C3bBb. We have determined the crystal structure of the three
      carboxyl-terminal complement control protein (CCP) modules of FH (FH18-20) that
      bind to C3b, and which additionally recognize polyanionic markers specific to
      self-surfaces. These CCPs harbour nearly 30 disease-linked missense mutations. We
      have also deployed small-angle X-ray scattering (SAXS) to investigate FH18-20
      flexibility in solution using FH18-20 and FH19-20 constructs. In the crystal
      lattice FH18-20 adopts a "J"-shape: A ~122-degree tilt between the structurally
      highly similar modules 18 and 19 precedes an extended, linear arrangement of
      modules 19 and 20 as observed in previously determined structures of these two
      modules alone. However, under solution conditions FH18-20 adopts multiple
      conformations mediated by flexibility between CCPs 18 and 19. We also pinpoint
      the locations of disease-associated missense mutations on the module 18 surface
      and discuss our data in the context of the C3b:FH interaction.

PMID- 22389687
TI  - Spatial localisation of actin filaments across developmental stages of the
      malaria parasite.
AB  - Actin dynamics have been implicated in a variety of developmental processes
      during the malaria parasite lifecycle. Parasite motility, in particular, is
      thought to critically depend on an actomyosin motor located in the outer pellicle
      of the parasite cell. Efforts to understand the diverse roles actin plays have,
      however, been hampered by an inability to detect microfilaments under native
      conditions. To visualise the spatial dynamics of actin we generated a parasite
      specific actin antibody that shows preferential recognition of filamentous actin
      and applied this tool to different lifecycle stages (merozoites, sporozoites and
      ookinetes) of the human and mouse malaria parasite species Plasmodium falciparum
      and P. berghei along with tachyzoites from the related apicomplexan parasite
      Toxoplasma gondii. Actin filament distribution was found associated with three
      core compartments: the nuclear periphery, pellicular membranes of motile or
      invasive parasite forms and in a ring-like distribution at the tight junction
      during merozoite invasion of erythrocytes in both human and mouse malaria
      parasites. Localisation at the nuclear periphery is consistent with an emerging
      role of actin in facilitating parasite gene regulation. During invasion, we show
      that the actin ring at the parasite-host cell tight junction is dependent on
      dynamic filament turnover. Super-resolution imaging places this ring posterior
      to, and not concentric with, the junction marker rhoptry neck protein 4. This
      implies motor force relies on the engagement of dynamic microfilaments at zones
      of traction, though not necessarily directly through receptor-ligand interactions
      at sites of adhesion during invasion. Combined, these observations extend current
      understanding of the diverse roles actin plays in malaria parasite development
      and apicomplexan cell motility, in particular refining understanding on the
      linkage of the internal parasite gliding motor with the extra-cellular milieu.

PMID- 22389688
TI  - Direct binding of a hepatitis C virus inhibitor to the viral capsid protein.
AB  - Over 130 million people are infected chronically with hepatitis C virus (HCV),
      which, together with HBV, is the leading cause of liver disease. Novel small
      molecule inhibitors of Hepatitis C virus (HCV) are needed to complement or
      replace current treatments based on pegylated interferon and ribavirin, which are
      only partially successful and plagued with side-effects. Assembly of the virion
      is initiated by the oligomerization of core, the capsid protein, followed by the
      interaction with NS5A and other HCV proteins. By screening for inhibitors of core
      dimerization, we previously discovered peptides and drug-like compounds that
      disrupt interactions between core and other HCV proteins, NS3 and NS5A, and block
      HCV production. Here we report that a biotinylated derivative of SL209, a
      prototype small molecule inhibitor of core dimerization (IC(50) of 2.80 uM) that
      inhibits HCV production with an EC(50) of 3.20 uM, is capable of penetrating HCV
      infected cells and tracking with core. Interaction between the inhibitors, core
      and other viral proteins was demonstrated by SL209-mediated affinity-isolation of
      HCV proteins from lysates of infected cells, or of the corresponding recombinant
      HCV proteins. SL209-like inhibitors of HCV core may form the basis of novel
      treatments of Hepatitis C in combination with other target-specific HCV drugs
      such as inhibitors of the NS3 protease, the NS5B polymerase, or the NS5A
      regulatory protein. More generally, our work supports the hypothesis that
      inhibitors of viral capsid formation might constitute a new class of potent
      antiviral agents, as was recently also shown for HIV capsid inhibitors.

PMID- 22389689
TI  - The effect of wind on the rate of heat loss from avian cup-shaped nests.
AB  - Forced convection can significantly influence the heat loss from birds and their
      offspring but effects may be reduced by using sheltered micro-sites such as
      cavities or constructing nests. The structural and thermal properties of the
      nests of two species, the spiny-cheeked honeyeater (Acanthagenys rufogularis) and
      yellow-throated miner (Manorina flavigula), were measured in relation to three
      wind speeds. Nest dimensions differ between the two species, despite the similar
      body mass of the incubating adults, however nest conductance is comparable. As
      wind speed increases, so does the rate of heat loss from the nests of both
      species, and further still during incubation recesses. The significance of forced
      convection through the nest is a near-doubling in heat production required by the
      parent, even when incubating at relatively low wind speeds. This provides
      confirmation that selecting a sheltered nest site is important for avian
      reproductive success.

PMID- 22389690
TI  - Development of high-density genetic maps for barley and wheat using a novel two
      enzyme genotyping-by-sequencing approach.
AB  - Advancements in next-generation sequencing technology have enabled whole genome
      re-sequencing in many species providing unprecedented discovery and
      characterization of molecular polymorphisms. There are limitations, however, to
      next-generation sequencing approaches for species with large complex genomes such
      as barley and wheat. Genotyping-by-sequencing (GBS) has been developed as a tool
      for association studies and genomics-assisted breeding in a range of species
      including those with complex genomes. GBS uses restriction enzymes for targeted
      complexity reduction followed by multiplex sequencing to produce high-quality
      polymorphism data at a relatively low per sample cost. Here we present a GBS
      approach for species that currently lack a reference genome sequence. We
      developed a novel two-enzyme GBS protocol and genotyped bi-parental barley and
      wheat populations to develop a genetically anchored reference map of identified
      SNPs and tags. We were able to map over 34,000 SNPs and 240,000 tags onto the
      Oregon Wolfe Barley reference map, and 20,000 SNPs and 367,000 tags on the
      Synthetic W9784 * Opata85 (SynOpDH) wheat reference map. To further evaluate GBS
      in wheat, we also constructed a de novo genetic map using only SNP markers from
      the GBS data. The GBS approach presented here provides a powerful method of
      developing high-density markers in species without a sequenced genome while
      providing valuable tools for anchoring and ordering physical maps and whole
      genome shotgun sequence. Development of the sequenced reference genome(s) will in
      turn increase the utility of GBS data enabling physical mapping of genes and
      haplotype imputation of missing data. Finally, as a result of low per-sample
      costs, GBS will have broad application in genomics-assisted plant breeding
      programs.

PMID- 22389691
TI  - Single molecule PCR reveals similar patterns of non-homologous DSB repair in
      tobacco and Arabidopsis.
AB  - DNA double strand breaks (DSBs) occur constantly in eukaryotes. These potentially
      lethal DNA lesions are repaired efficiently by two major DSB repair pathways:
      homologous recombination and non-homologous end joining (NHEJ). We investigated
      NHEJ in Arabidopsis thaliana and tobacco (Nicotiana tabacum) by introducing DNA
      double-strand breaks through inducible expression of I-SceI, followed by
      amplification of individual repair junction sequences by single-molecule PCR.
      Using this process over 300 NHEJ repair junctions were analysed in each species.
      In contrast to previously published variation in DSB repair between Arabidopsis
      and tobacco, the two species displayed similar DSB repair profiles in our
      experiments. The majority of repair events resulted in no loss of sequence and
      small (1-20 bp) deletions occurred at a minority (25-45%) of repair junctions.
      Approximately ~1.5% of the observed repair events contained larger deletions (>20
      bp) and a similar percentage contained insertions. Strikingly, insertion events
      in tobacco were associated with large genomic deletions at the site of the DSB
      that resulted in increased micro-homology at the sequence junctions suggesting
      the involvement of a non-classical NHEJ repair pathway. The generation of DSBs
      through inducible expression of I-SceI, in combination with single molecule PCR,
      provides an effective and efficient method for analysis of individual repair
      junctions and will prove a useful tool in the analysis of NHEJ.

PMID- 22389692
TI  - Nitric oxide signalling augments neuronal voltage-gated L-type (Ca(v)1) and P/q
      type (Ca(v)2.1) channels in the mouse medial nucleus of the trapezoid body.
AB  - Nitric Oxide (NO) is a diffusible second messenger that modulates ion channels,
      intrinsic excitability and mediates synaptic plasticity. In light of its activity
      dependent generation in the principal neurons of the medial nucleus of the
      trapezoid body (MNTB), we have investigated its potential modulatory effects on
      native voltage-gated calcium channels (Ca(V)) within this nucleus. Whole-cell
      patch recordings were made from brain slices from P13-15 CBA mice. Slices were
      incubated with the inhibitor of neuronal nitric oxide synthase (nNOS) 7
      nitroindazole (10 uM) and pharmacological blockers used to isolate Ca(2+) current
      subtypes. Unpaired observations in the presence and absence of the NO-donors
      sodium nitroprusside (SNP, 100 uM) or Diethyl-ammonium-nonoate (DEA, 100 uM) were
      made to elucidate NO-dependent modulation of the expressed Ca(V) subtypes. A
      differential effect of NO on the calcium channel subtypes was observed: Ca(V)1
      and Ca(V)2.1 (L+R- and P/Q+R-type) conductances were potentiated, whereas N+R
      type (Ca(V)2.2) and R-type (Ca(V)2.3) current amplitudes were unaffected. L+R
      type currents increased from 0.36 +/- 0.04 nA to 0.64 +/- 0.11 nA and P/Q+R-type
      from 0.55 +/- 0.09 nA to 0.94 +/- 0.05 nA, thereby changing the balance and
      relative contribution of each subtype to the whole cell calcium current. In
      addition, N+R-type half-activation voltage was left shifted following NO
      exposure. NO-dependent modulation of P/Q+R and N+R-type, but not L+R-type,
      channels was removed by inhibition of soluble guanylyl cyclase (sGC) activity.
      This data demonstrates a differential effect of NO signalling on voltage-gated
      calcium entry, by distinct NO-dependent pathways.

PMID- 22389693
TI  - Ischemic preconditioning in the animal kidney, a systematic review and meta
      analysis.
AB  - Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not
      yet been translated successfully into clinical practice, in spite of promising
      results in animal studies. We performed a unique systematic review and meta
      analysis of animal studies to identify factors modifying IPC efficacy in renal
      ischemia/reperfusion injury (IRI), in order to enhance the design of future
      (clinical) studies. An electronic literature search for animal studies on IPC in
      renal IRI yielded fifty-eight studies which met our inclusion criteria. We
      extracted data for serum creatinine, blood urea nitrogen and histological renal
      damage, as well as study quality indicators. Meta-analysis showed that IPC
      reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD
      1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89,
      1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were
      the window of protection (<24 h = early vs. >= 24 h = late) and animal species
      (rat vs. mouse). No difference in efficacy between local and remote IPC was
      observed. In conclusion, our findings show that IPC effectively reduces renal
      damage after IRI, with higher efficacy in the late window of protection. However,
      there is a large gap in study data concerning the optimal window of protection,
      and IPC efficacy may differ per animal species. Moreover, current clinical trials
      on RIPC may not be optimally designed, and our findings identify a need for
      further standardization of animal experiments.

PMID- 22389694
TI  - Significant association of estrogen receptor binding site variation with bipolar
      disorder in females.
AB  - Major depression is nearly twice as prevalent in women compared to men. In
      bipolar disorder, depressive episodes have been reported to be more common
      amongst female patients. Furthermore, periods of depression often correlate with
      periods of hormonal fluctuations. A link between hormone signaling and these mood
      disorders has, therefore, been suggested to exist in many studies. Estrogen, one
      of the primary female sex hormones, mediates its effect mostly by binding to
      estrogen receptors (ERs). Nuclear ERs function as transcription factors and
      regulate gene transcription by binding to specific DNA sequences. A nucleotide
      change in the binding sequence might alter the binding efficiency, which could
      affect transcription levels of nearby genes. In order to investigate if variation
      in ER DNA-binding sequences may be involved in mood disorders, we conducted a
      genome-wide study of ER DNA-binding in patients diagnosed with major depression
      or bipolar disorder. Association studies were performed within each gender
      separately and the results were corrected for multiple testing by the Bonferroni
      method. In the female bipolar disorder material a significant association result
      was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95%
      confidence interval (CI) 0.570-0.814), a single nucleotide polymorphism (SNP)
      placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females
      with a specific genotype at this SNP may be more vulnerable to fluctuating
      estrogen levels, which may then act as a triggering factor for bipolar disorder.

PMID- 22389695
TI  - Serum microRNA biomarkers for detection of non-small cell lung cancer.
AB  - Non small cell lung cancer (NSCLC) is the leading cause of cancer-related
      mortality world-wide and the majority of cases are diagnosed at late stages of
      disease. There is currently no cost-effective screening test for NSCLC, and the
      development of such a test is a public health imperative. Recent studies have
      suggested that chest computed tomography screening of patients at high risk of
      lung cancer can increase survival from disease, however, the cost effectiveness
      of such screening has not been established. In this Phase I/II biomarker study we
      examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT
      qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive
      NSCLC patients and 20 healthy controls. Receiver operating characteristic curves
      (ROC) and area under the curve were used to identify differentially expressed
      miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA
      candidates were further validated in sera from an additional 55 NSCLC patients
      and 75 healthy controls. Examination of miRNA expression levels in serum from a
      multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy
      controls) identified differentially expressed miRNAs. A combination of two
      differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate
      NSCLC from healthy controls with sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon
      further testing on additional 130 subjects (55 NSCLC and 75 healthy controls),
      this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73-0.91),
      sensitivity of 100% (95% CI; 0.93-1.0), NPV of 100%, and PPV of 82%. These data
      provide evidence that serum miRNAs have the potential to be sensitive, cost
      effective biomarkers for the early detection of NSCLC. Further testing in a Phase
      III biomarker study in is necessary for validation of these results.

PMID- 22389697
TI  - Spontaneous gender categorization in masking and priming studies: key for
      distinguishing Jane from John Doe but not Madonna from Sinatra.
AB  - Facial recognition is key to social interaction, however with unfamiliar faces
      only generic information, in the form of facial stereotypes such as gender and
      age is available. Therefore is generic information more prominent in unfamiliar
      versus familiar face processing? In order to address the question we tapped into
      two relatively disparate stages of face processing. At the early stages of
      encoding, we employed perceptual masking to reveal that only perception of
      unfamiliar face targets is affected by the gender of the facial masks. At the
      semantic end; using a priming paradigm, we found that while to-be-ignored
      unfamiliar faces prime lexical decisions to gender congruent stereotypic words,
      familiar faces do not. Our findings indicate that gender is a more salient
      dimension in unfamiliar relative to familiar face processing, both in early
      perceptual stages as well as later semantic stages of person construal.

PMID- 22389696
TI  - Neutrophil extracellular traps directly induce epithelial and endothelial cell
      death: a predominant role of histones.
AB  - Neutrophils play an important role in innate immunity by defending the host
      organism against invading microorganisms. Antimicrobial activity of neutrophils
      is mediated by release of antimicrobial peptides, phagocytosis as well as
      formation of neutrophil extracellular traps (NET). These structures are composed
      of DNA, histones and granular proteins such as neutrophil elastase and
      myeloperoxidase. This study focused on the influence of NET on the host cell
      functions, particularly on human alveolar epithelial cells as the major cells
      responsible for gas exchange in the lung. Upon direct interaction with epithelial
      and endothelial cells, NET induced cytotoxic effects in a dose-dependent manner,
      and digestion of DNA in NET did not change NET-mediated cytotoxicity. Pre
      incubation of NET with antibodies against histones, with polysialic acid or with
      myeloperoxidase inhibitor but not with elastase inhibitor reduced NET-mediated
      cytotoxicity, suggesting that histones and myeloperoxidase are responsible for
      NET-mediated cytotoxicity. Although activated protein C (APC) did decrease the
      histone-induced cytotoxicity in a purified system, it did not change NET-induced
      cytotoxicity, indicating that histone-dependent cytotoxicity of NET is protected
      against APC degradation. Moreover, in LPS-induced acute lung injury mouse model,
      NET formation was documented in the lung tissue as well as in the bronchoalveolar
      lavage fluid. These data reveal the important role of protein components in NET,
      particularly histones, which may lead to host cell cytotoxicity and may be
      involved in lung tissue destruction.

PMID- 22389698
TI  - A catalytic mechanism for cysteine N-terminal nucleophile hydrolases, as revealed
      by free energy simulations.
AB  - The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes
      specialized in the hydrolytic cleavage of amide bonds. Even though several
      members of this family are emerging as innovative drug targets for cancer,
      inflammation, and pain, the processes through which they catalyze amide
      hydrolysis remains poorly understood. In particular, the catalytic reactions of
      cysteine Ntn-hydrolases have never been investigated from a mechanistic point of
      view. In the present study, we used free energy simulations in the quantum
      mechanics/molecular mechanics framework to determine the reaction mechanism of
      amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated
      bile acid hydrolase (CBAH). The computational analyses, which were confirmed in
      water and using different CBAH mutants, revealed the existence of a chair-like
      transition state, which might be one of the specific features of the catalytic
      cycle of Ntn-hydrolases. Our results offer new insights on Ntn-mediated
      hydrolysis and suggest possible strategies for the creation of therapeutically
      useful inhibitors.

PMID- 22389699
TI  - How well do randomized trials inform decision making: systematic review using
      comparative effectiveness research measures on acupuncture for back pain.
AB  - BACKGROUND: For Comparative Effectiveness Research (CER) there is a need to
      develop scales for appraisal of available clinical research. Aims were to 1) test
      the feasibility of applying the pragmatic-explanatory continuum indicator summary
      tool and the six CER defining characteristics of the Institute of Medicine to
      RCTs of acupuncture for treatment of low back pain, and 2) evaluate the extent to
      which the evidence from these RCTs is relevant to clinical and health policy
      decision making. METHODS: We searched Medline, the AcuTrialsTM Database to
      February 2011 and reference lists and included full-report randomized trials in
      English that compared needle acupuncture with a conventional treatment in adults
      with non-specific acute and/or chronic low back pain and restricted to those with
      >=30 patients in the acupuncture group. Papers were evaluated by 5 raters.
      PRINCIPAL FINDINGS: From 119 abstracts, 44 full-text publications were screened
      and 10 trials (4,901 patients) were evaluated. Due to missing information and
      initial difficulties in operationalizing the scoring items, the first scoring
      revealed inter-rater and inter-item variance (intraclass correlations 0.02-0.60),
      which improved after consensus discussions to 0.20-1.00. The 10 trials were found
      to cover the efficacy-effectiveness continuum; those with more flexible
      acupuncture and no placebo control scored closer to effectiveness. CONCLUSION:
      Both instruments proved useful, but need further development. In addition,
      CONSORT guidelines for reporting pragmatic trials should be expanded. Most
      studies in this review already reflect the movement towards CER and similar
      approaches can be taken to evaluate comparative effectiveness relevance of RCTs
      for other treatments.

PMID- 22389700
TI  - Glucose transporter 1 and monocarboxylate transporters 1, 2, and 4 localization
      within the glial cells of shark blood-brain-barriers.
AB  - Although previous studies showed that glucose is used to support the metabolic
      activity of the cartilaginous fish brain, the distribution and expression levels
      of glucose transporter (GLUT) isoforms remained undetermined.
      Optic/ultrastructural immunohistochemistry approaches were used to determine the
      expression of GLUT1 in the glial blood-brain barrier (gBBB). GLUT1 was observed
      solely in glial cells; it was primarily located in end-feet processes of the
      gBBB. Western blot analysis showed a protein with a molecular mass of 50 kDa, and
      partial sequencing confirmed GLUT1 identity. Similar approaches were used to
      demonstrate increased GLUT1 polarization to both apical and basolateral membranes
      in choroid plexus epithelial cells. To explore monocarboxylate transporter (MCT)
      involvement in shark brain metabolism, the expression of MCTs was analyzed. MCT1,
      2 and 4 were expressed in endothelial cells; however, only MCT1 and MCT4 were
      present in glial cells. In neurons, MCT2 was localized at the cell membrane
      whereas MCT1 was detected within mitochondria. Previous studies demonstrated that
      hypoxia modified GLUT and MCT expression in mammalian brain cells, which was
      mediated by the transcription factor, hypoxia inducible factor-1. Similarly, we
      observed that hypoxia modified MCT1 cellular distribution and MCT4 expression in
      shark telencephalic area and brain stem, confirming the role of these
      transporters in hypoxia adaptation. Finally, using three-dimensional
      ultrastructural microscopy, the interaction between glial end-feet and leaky
      blood vessels of shark brain was assessed in the present study. These data
      suggested that the brains of shark may take up glucose from blood using a
      different mechanism than that used by mammalian brains, which may induce
      astrocyte-neuron lactate shuttling and metabolic coupling as observed in
      mammalian brain. Our data suggested that the structural conditions and expression
      patterns of GLUT1, MCT1, MCT2 and MCT4 in shark brain may establish the molecular
      foundation of metabolic coupling between glia and neurons.

PMID- 22389701
TI  - Adora2b adenosine receptor engagement enhances regulatory T cell abundance during
      endotoxin-induced pulmonary inflammation.
AB  - Anti-inflammatory signals play an essential role in constraining the magnitude of
      an inflammatory response. Extracellular adenosine is a critical tissue-protective
      factor, limiting the extent of inflammation. Given the potent anti-inflammatory
      effects of extracellular adenosine, we sought to investigate how extracellular
      adenosine regulates T cell activation and differentiation. Adenosine receptor
      activation by a pan adenosine-receptor agonist enhanced the abundance of murine
      regulatory T cells (Tregs), a cell type critical in constraining inflammation.
      Gene expression studies in both naive CD4 T cells and Tregs revealed that these
      cells expressed multiple adenosine receptors. Based on recent studies implicating
      the Adora2b in endogenous anti-inflammatory responses during acute inflammation,
      we used a pharmacologic approach to specifically activate Adora2b. Indeed, these
      studies revealed robust enhancement of Treg differentiation in wild-type mice,
      but not in Adora2b(-/-) T cells. Finally, when we subjected Adora2b-deficient
      mice to endotoxin-induced pulmonary inflammation, we found that these mice
      experienced more severe inflammation, characterized by increased cell recruitment
      and increased fluid leakage into the airways. Notably, Adora2b-deficient mice
      failed to induce Tregs after endotoxin-induced inflammation and instead had an
      enhanced recruitment of pro-inflammatory effector T cells. In total, these data
      indicate that the Adora2b adenosine receptor serves a potent anti-inflammatory
      role, functioning at least in part through the enhancement of Tregs, to limit
      inflammation.

PMID- 22389702
TI  - Capacity for absorption of water-soluble secondary metabolites greater in birds
      than in rodents.
AB  - Plant secondary metabolites (SMs) are pervasive in animal foods and potentially
      influence feeding behavior, interspecies interactions, and the distribution and
      abundance of animals. Some of the major classes of naturally occurring SMs in
      plants include many water-soluble compounds in the molecular size range that
      could cross the intestinal epithelium via the paracellular space by diffusion or
      solvent drag. There are differences among species in paracellular permeability.
      Using Middle Eastern rodent and avian consumers of fruits containing SMs, we
      tested the hypothesis that avian species would have significantly higher
      paracellular permeability than rodent species. Permeability in intact animals was
      assessed using standard pharmacological methodology to measure absorption of two
      radiolabeled, inert, neutral water-soluble probes that do not interact with
      intestinal nutrient transporters, L-arabinose (M(r) = 150.1 Da) and lactulose
      (M(r) = 342.3 Da). We also measured absorption of labeled 3-O-methyl-D-glucose
      (3OMD-glucose; M(r) = 194.2 Da), which is a nonmetabolized analogue of D-glucose
      that is passively absorbed through the paracellular space but also transported
      across the enterocyte membranes. Most glucose was absorbed by all species, but
      arabinose fractional absorption (f) was nearly three times higher in birds
      (1.03+/-0.17, n = 15 in two species) compared to rodents (0.37+/-0.06, n = 10 in
      two species) (P<0.001). Surprisingly, the apparent rates of absorption in birds
      of arabinose exceeded those of 3OMD-glucose. Our findings are in agreement with
      previous work showing that the paracellular pathway is more prominent in birds
      relative to nonflying mammals, and suggests that birds may be challenged by
      greater absorption of water-soluble, dietary SMs. The increased expression of the
      paracellular pathway in birds hints at a tradeoff: the free energy birds gain by
      absorbing water-soluble nutrients passively may be offset by the metabolic
      demands placed on them to eliminate concomitantly absorbed SMs.

PMID- 22389703
TI  - SM934 treated lupus-prone NZB * NZW F1 mice by enhancing macrophage interleukin
      10 production and suppressing pathogenic T cell development.
AB  - BACKGROUND: Artemisinin and its derivatives were reported to possess strong
      regulatory effects on inflammation and autoimmune diseases. This study was
      designed to examine the therapeutic effects and underlying mechanisms of SM934, a
      water-soluble artemisinin analogue, on lupus-prone female NZB * NZW F(1) mice.
      METHODOLOGY/PRINCIPAL FINDINGS: NZB/W F(1) mice were treated orally with SM934
      for 3 or 6 months respectively to investigate the effect on clinical
      manifestations and immunological correlates. To further explore the mechanisms of
      SM934, ovalbumin (OVA)-immunized or interferon (IFN)-gamma-elicited C57BL/6 mice
      were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed
      the progression of glomerulonephritis and increased the survival rate of NZB/W
      F(1) mice. Clinical improvement was accompanied with decreased Th1-related anti
      double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and
      increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment
      also suppressed the accumulation of effector/memory T cells, induced the
      apoptosis of CD4(+) T cells, while enhancing the development of regulatory T
      cells in NZB/W F(1) mice. In addition, SM934 treatment promoted the IL-10
      production of macrophages from NZB/W F(1) mice, OVA-immunized C57BL/6 mice and
      IFN-gamma-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from
      primary macrophages stimulated with IFN-gamma. CONCLUSIONS/SIGNIFICANCE: The
      results of this study demonstrated that artemisinin analogue SM934 had
      therapeutic effects on lupus-prone female NZB/W F(1) mice by inhibiting the
      pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL
      10 production.

PMID- 22389704
TI  - Repertoire of intensive care unit pneumonia microbiota.
AB  - Despite the considerable number of studies reported to date, the causative agents
      of pneumonia are not completely identified. We comprehensively applied modern and
      traditional laboratory diagnostic techniques to identify microbiota in patients
      who were admitted to or developed pneumonia in intensive care units (ICUs).
      During a three-year period, we tested the bronchoalveolar lavage (BAL) of
      patients with ventilator-associated pneumonia, community-acquired pneumonia, non
      ventilator ICU pneumonia and aspiration pneumonia, and compared the results with
      those from patients without pneumonia (controls). Samples were tested by
      amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and
      by PCR to target specific pathogens. We also included culture, amoeba co-culture,
      detection of antibodies to selected agents and urinary antigen tests. Based on
      molecular testing, we identified a wide repertoire of 160 bacterial species of
      which 73 have not been previously reported in pneumonia. Moreover, we found 37
      putative new bacterial phylotypes with a 16S rDNA gene divergence >= 98% from
      known phylotypes. We also identified 24 fungal species of which 6 have not been
      previously reported in pneumonia and 7 viruses. Patients can present up to 16
      different microorganisms in a single BAL (mean +/- SD; 3.77 +/- 2.93). Some
      pathogens considered to be typical for ICU pneumonia such as Pseudomonas
      aeruginosa and Streptococcus species can be detected as commonly in controls as
      in pneumonia patients which strikingly highlights the existence of a core
      pulmonary microbiota. Differences in the microbiota of different forms of
      pneumonia were documented.

PMID- 22389705
TI  - Serum concentrations of soluble Flt-1 are decreased among women with a viable
      fetus and no symptoms of miscarriage destined for pregnancy loss.
AB  - Miscarriage is the most common complication of pregnancy. Pre-clinical
      miscarriage has an estimated incidence of 30%, whilst clinical miscarriage has an
      incidence of 12-15%. Two thirds of pregnancies lost to miscarriage are believed
      to be attributable to defective placentation, thus a number of studies have
      sought to identify markers of defective placentation that could be used as
      clinical biomarkers of miscarriage. Decreased soluble FMS-like tyrosine kinase-1
      (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) in the
      maternal circulation during the first trimester have recently been proposed as
      potential markers of pregnancy loss. However, in these studies clinical samples
      were only obtained once women had presented with symptoms of miscarriage. In this
      study we prospectively screened serum samples collected from asymptomatic women
      with a viable fetus. We assessed maternal serum levels of sFlt1, PlGF and sEng
      across the first trimester of normal pregnancy and compared levels between women
      who continued to a live birth, to those who subsequently miscarried. Both sFlt1
      and PlGF significantly (p<=0.05) increased across gestation in normal pregnancy
      with serum levels rising from 0.65+/-0.12 ng/ml at 6 weeks to 1.85+/-0.24 ng/ml
      at 12 weeks for sFlt1, and 57.2+/-19.2 pg/ml to 106+/-22.7 pg/ml for PlGF. sEng
      remained unchanged throughout the the first trimester. Importantly we detected a
      significant (35%, p<=0.05) decrease in sFlt1 levels between our control and
      miscarriage cohort, however there was significant overlap between cases and
      controls, suggesting serum sFlt1 is unlikely to be useful as a clinical biomarker
      in asymptomatic women. Nevertheless, our data suggests a dysregulation of
      angiogenic factors may be involved in the pathophysiology of miscarriage.

PMID- 22389706
TI  - Absence of RIP140 reveals a pathway regulating glut4-dependent glucose uptake in
      oxidative skeletal muscle through UCP1-mediated activation of AMPK.
AB  - Skeletal muscle constitutes the major site of glucose uptake leading to increased
      removal of glucose from the circulation in response to insulin. Type 2 diabetes
      and obesity are often associated with insulin resistance that can be counteracted
      by exercise or the use of drugs increasing the relative proportion of oxidative
      fibers. RIP140 is a transcriptional coregulator with a central role in metabolic
      tissues and we tested the effect of modulating its level of expression on muscle
      glucose and lipid metabolism in two mice models. Here, we show that although
      RIP140 protein is expressed at the same level in both oxidative and glycolytic
      muscles, it inhibits both fatty acid and glucose utilization in a fiber-type
      dependent manner. In RIP140-null mice, fatty acid utilization increases in the
      extensor digitorum longus and this is associated with elevated expression of
      genes implicated in fatty acid binding and transport. In the RIP140-null soleus,
      depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with
      no change in Akt activity. AMPK phosphorylation/activity is inhibited in the
      soleus of RIP140 transgenic mice and increased in RIP140-null soleus. This is
      associated with increased UCP1 expression and mitochondrial uncoupling revealing
      the existence of a signaling pathway controlling insulin-independent glucose
      uptake in the soleus of RIP140-null mice. In conclusion, our findings reinforce
      the participation of RIP140 in the maintenance of energy homeostasis by acting as
      an inhibitor of energy production and particularly point to RIP140 as a promising
      therapeutic target in the treatment of insulin resistance.

PMID- 22389707
TI  - Proteomic profile of reversible protein oxidation using PROP, purification of
      reversibly oxidized proteins.
AB  - Signal transduction pathways that are modulated by thiol oxidation events are
      beginning to be uncovered, but these discoveries are limited by the availability
      of relatively few analytical methods to examine protein oxidation compared to
      other signaling events such as protein phosphorylation. We report here the
      coupling of PROP, a method to purify reversibly oxidized proteins, with the
      proteomic identification of the purified mixture using mass spectrometry. A gene
      ontology (GO), KEGG enrichment and Wikipathways analysis of the identified
      proteins indicated a significant enrichment in proteins associated with both
      translation and mRNA splicing. This methodology also enabled the identification
      of some of the specific cysteine residue targets within identified proteins that
      are reversibly oxidized by hydrogen peroxide treatment of intact cells. From
      these identifications, we determined a potential consensus sequence motif
      associated with oxidized cysteine residues. Furthermore, because we identified
      proteins and specific sites of oxidation from both abundant proteins and from far
      less abundant signaling proteins (e.g. hepatoma derived growth factor,
      prostaglandin E synthase 3), the results suggest that the PROP procedure was
      efficient. Thus, this PROP-proteomics methodology offers a sensitive means to
      identify biologically relevant redox signaling events that occur within intact
      cells.

PMID- 22389708
TI  - Standard colonic lavage alters the natural state of mucosal-associated microbiota
      in the human colon.
AB  - BACKGROUND & AIMS: Past studies of the human intestinal microbiota are
      potentially confounded by the common practice of using bowel-cleansing
      preparations. We examined if colonic lavage changes the natural state of enteric
      mucosal-adherent microbes in healthy human subjects. METHODS: Twelve healthy
      individuals were divided into three groups; experimental group, control group
      one, and control group two. Subjects in the experimental group underwent an un
      prepped flexible sigmoidoscopy with biopsies. Within two weeks, subjects were
      given a standard polyethylene glycol-based bowel cleansing preparation followed
      by a second flexible sigmoidoscopy. Subjects in control group one underwent two
      un-prepped flexible sigmoidoscopies within one week. Subjects in the second
      control group underwent an un-prepped flexible sigmoidoscopy followed by a second
      flexible sigmoidoscopy after a 24-hour clear liquid diet within one week. The
      mucosa-associated microbial communities from the two procedures in each subject
      were compared using 16S rRNA gene based terminal restriction fragment length
      polymorphism (T-RFLP), and library cloning and sequencing. RESULTS: Clone library
      sequencing analysis showed that there were changes in the composition of the
      mucosa-associated microbiota in subjects after colonic lavage. These changes were
      not observed in our control groups. Standard bowel preparation altered the
      diversity of mucosa-associated microbiota. Taxonomic classification did not
      reveal significant changes at the phylum level, but there were differences
      observed at the genus level. CONCLUSION: Standard bowel cleansing preparation
      altered the mucosal-adherent microbiota in all of our subjects, although the
      degree of change was variable. These findings underscore the importance of
      considering the confounding effects of bowel preparation when designing
      experiments exploring the gut microbiota.

PMID- 22389709
TI  - Structural stability of human protein tyrosine phosphatase rho catalytic domain:
      effect of point mutations.
AB  - Protein tyrosine phosphatase rho (PTPrho) belongs to the classical receptor type
      IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine
      phosphatase in human cancer. There are evidences to suggest that PTPrho may act
      as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be
      observed in diverse diseases, such as diabetes, immune deficiencies and cancer.
      PTPrho variants in the catalytic domain have been identified in cancer tissues.
      These natural variants are nonsynonymous single nucleotide polymorphisms,
      variations of a single nucleotide occurring in the coding region and leading to
      amino acid substitutions. In this study we investigated the effect of amino acid
      substitution on the structural stability and on the activity of the membrane
      proximal catalytic domain of PTPrho. We expressed and purified as soluble
      recombinant proteins some of the mutants of the membrane-proximal catalytic
      domain of PTPrho identified in colorectal cancer and in the single nucleotide
      polymorphisms database. The mutants show a decreased thermal and thermodynamic
      stability and decreased activation energy relative to phosphatase activity, when
      compared to wild- type. All the variants show three-state equilibrium unfolding
      transitions similar to that of the wild- type, with the accumulation of a folding
      intermediate populated at ~4.0 M urea.

PMID- 22389710
TI  - Cellular traction stresses increase with increasing metastatic potential.
AB  - Cancer cells exist in a mechanically and chemically heterogeneous
      microenvironment which undergoes dynamic changes throughout neoplastic
      progression. During metastasis, cells from a primary tumor acquire
      characteristics that enable them to escape from the primary tumor and migrate
      through the heterogeneous stromal environment to establish secondary tumors.
      Despite being linked to poor prognosis, there are no direct clinical tests
      available to diagnose the likelihood of metastasis. Moreover, the physical
      mechanisms employed by metastatic cancer cells to migrate are poorly understood.
      Because metastasis of most solid tumors requires cells to exert force to
      reorganize and navigate through dense stroma, we investigated differences in
      cellular force generation between metastatic and non-metastatic cells. Using
      traction force microscopy, we found that in human metastatic breast, prostate and
      lung cancer cell lines, traction stresses were significantly increased compared
      to non-metastatic counterparts. This trend was recapitulated in the isogenic
      MCF10AT series of breast cancer cells. Our data also indicate that increased
      matrix stiffness and collagen density promote increased traction forces, and that
      metastatic cells generate higher forces than non-metastatic cells across all
      matrix properties studied. Additionally, we found that cell spreading for these
      cell lines has a direct relationship with collagen density, but a biphasic
      relationship with substrate stiffness, indicating that cell area alone does not
      dictate the magnitude of traction stress generation. Together, these data suggest
      that cellular contractile force may play an important role in metastasis, and
      that the physical properties of the stromal environment may regulate cellular
      force generation. These findings are critical for understanding the physical
      mechanisms of metastasis and the role of the extracellular microenvironment in
      metastatic progression.

PMID- 22389711
TI  - Identification and differentiation of the twenty six bluetongue virus serotypes
      by RT-PCR amplification of the serotype-specific genome segment 2.
AB  - Bluetongue (BT) is an arthropod-borne viral disease, which primarily affects
      ruminants in tropical and temperate regions of the world. Twenty six bluetongue
      virus (BTV) serotypes have been recognised worldwide, including nine from Europe
      and fifteen in the United States. Identification of BTV serotype is important for
      vaccination programmes and for BTV epidemiology studies. Traditional typing
      methods (virus isolation and serum or virus neutralisation tests (SNT or VNT))
      are slow (taking weeks, depend on availability of reference virus-strains or
      antisera) and can be inconclusive. Nucleotide sequence analyses and phylogenetic
      comparisons of genome segment 2 (Seg-2) encoding BTV outer-capsid protein VP2
      (the primary determinant of virus serotype) were completed for reference strains
      of BTV-1 to 26, as well as multiple additional isolates from different geographic
      and temporal origins. The resulting Seg-2 database has been used to develop rapid
      (within 24 h) and reliable RT-PCR-based typing assays for each BTV type. Multiple
      primer-pairs (at least three designed for each serotype) were widely tested,
      providing an initial identification of serotype by amplification of a cDNA
      product of the expected size. Serotype was confirmed by sequencing of the cDNA
      amplicons and phylogenetic comparisons to previously characterised reference
      strains. The results from RT-PCR and sequencing were in perfect agreement with
      VNT for reference strains of all 26 BTV serotypes, as well as the field isolates
      tested. The serotype-specific primers showed no cross-amplification with
      reference strains of the remaining 25 serotypes, or multiple other isolates of
      the more closely related heterologous BTV types. The primers and RT-PCR assays
      developed in this study provide a rapid, sensitive and reliable method for the
      identification and differentiation of the twenty-six BTV serotypes, and will be
      updated periodically to maintain their relevance to current BTV distribution and
      epidemiology (http://www.reoviridae.org/dsRNA_virus_proteins/ReoID/rt-pcr
      primers.htm).

PMID- 22389712
TI  - Epizootic emergence of Usutu virus in wild and captive birds in Germany.
AB  - This study aimed to identify the causative agent of mass mortality in wild and
      captive birds in southwest Germany and to gather insights into the phylogenetic
      relationship and spatial distribution of the pathogen. Since June 2011, 223 dead
      birds were collected and tested for the presence of viral pathogens. Usutu virus
      (USUV) RNA was detected by real-time RT-PCR in 86 birds representing 6 species.
      The virus was isolated in cell culture from the heart of 18 Blackbirds (Turdus
      merula). USUV-specific antigen was demonstrated by immunohistochemistry in brain,
      heart, liver, and lung of infected Blackbirds. The complete polyprotein coding
      sequence was obtained by deep sequencing of liver and spleen samples of a dead
      Blackbird from Mannheim (BH65/11-02-03). Phylogenetic analysis of the German USUV
      strain BH65/11-02-03 revealed a close relationship with strain Vienna that caused
      mass mortality among birds in Austria in 2001. Wild birds from lowland river
      valleys in southwest Germany were mainly affected by USUV, but also birds kept in
      aviaries. Our data suggest that after the initial detection of USUV in German
      mosquitoes in 2010, the virus spread in 2011 and caused epizootics among wild and
      captive birds in southwest Germany. The data also indicate an increased risk of
      USUV infections in humans in Germany.

PMID- 22389713
TI  - Metabolic and proteomic profiling of diapause in the aphid parasitoid Praon
      volucre.
AB  - BACKGROUND: Diapause, a condition of developmental arrest and metabolic
      depression exhibited by a wide range of animals is accompanied by complex
      physiological and biochemical changes that generally enhance environmental stress
      tolerance and synchronize reproduction. Even though some aspects of diapause have
      been well characterized, very little is known about the full range of molecular
      and biochemical modifications underlying diapause in non-model organisms.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study we focused on the parasitic wasp,
      Praon volucre that exhibits a pupal diapause in response to environmental
      signals. System-wide metabolic changes occurring during diapause were
      investigated using GC-MS metabolic fingerprinting. Moreover, proteomic changes
      were studied in diapausing versus non-diapausing phenotypes using a combination
      of two-dimensional differential gel electrophoresis (2D-DIGE) and mass
      spectrometry. We found a reduction of Krebs cycle intermediates which most likely
      resulted from the metabolic depression. Glycolysis was galvanized, probably to
      favor polyols biosynthesis. Diapausing parasitoids accumulated high levels of
      cryoprotective polyols, especially sorbitol. A large set of proteins were
      modulated during diapause and these were involved in various functions such as
      remodeling of cytoskeleton and cuticle, stress tolerance, protein turnover, lipid
      metabolism and various metabolic enzymes. CONCLUSIONS/SIGNIFICANCE: The results
      presented here provide some first clues about the molecular and biochemical
      events that characterize the diapause syndrome in aphid parasitoids. These data
      are useful for probing potential commonality of parasitoids diapause with other
      taxa and they will help creating a general understanding of diapause
      underpinnings and a background for future interpretations.

PMID- 22389714
TI  - Effects of reproductive status, social rank, sex and group size on vigilance
      patterns in Przewalski's gazelle.
AB  - BACKGROUND: Quantifying vigilance and exploring the underlying mechanisms has
      been the subject of numerous studies. Less attention has focused on the complex
      interplay between contributing factors such as reproductive status, social rank,
      sex and group size. Reproductive status and social rank are of particular
      interest due to their association with mating behavior. Mating activities in
      rutting season may interfere with typical patterns of vigilance and possibly
      interact with social rank. In addition, balancing the tradeoff between vigilance
      and life maintenance may represent a challenge for gregarious ungulate species
      rutting under harsh winter conditions. We studied vigilance patterns in the
      endangered Przewalski's gazelle (Procapra przewalskii) during both the rutting
      and non-rutting seasons to examine these issues. METHODOLOGY/PRINCIPAL FINDINGS:
      Field observations were carried out with focal sampling during rutting and non
      rutting season in 2008-2009. Results indicated a complex interplay between
      reproductive status, social rank, sex and group size in determining vigilance in
      this species. Vigilance decreased with group size in female but not in male
      gazelles. Males scanned more frequently and thus spent more time vigilant than
      females. Compared to non-rutting season, gazelles increased time spent scanning
      at the expense of bedding in rutting season. During the rutting season,
      territorial males spent a large proportion of time on rutting activities and were
      less vigilant than non-territorial males. Although territorial males may share
      collective risk detection with harem females, we suggest that they are probably
      more vulnerable to predation because they seemed reluctant to leave rut stands
      under threats. CONCLUSIONS/SIGNIFICANCE: Vigilance behavior in Przewalski's
      gazelle was significantly affected by reproductive status, social rank, sex,
      group size and their complex interactions. These findings shed light on the
      mechanisms underlying vigilance patterns and the tradeoff between vigilance and
      other crucial activities.

PMID- 22389715
TI  - A large population histology study showing the lack of association between ALT
      elevation and significant fibrosis in chronic hepatitis B.
AB  - OBJECTIVE: We determined the association between various clinical parameters and
      significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg
      negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319
      treatment-naive CHB patients. Histologic assessment was based on the Knodell
      histologic activity index for necroinflammation and the Ishak fibrosis staging
      for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were
      recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%)
      HBeAg-positive patients with normal ALT had significant histologic abnormalities
      (necroinflammation grading >= 7 or fibrosis score >= 3). There was a significant
      difference in fibrosis scores among HBeAg-positive patients with an ALT level
      within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a
      normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate
      aminotransferase and platelet count were independent predictors of significant
      fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis
      (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were
      predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015
      respectively). An elevated ALT was not predictive of significant fibrosis for
      HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no
      significant difference in fibrosis staging among ALT 1-2 * upper limit of normal
      (ULN) and > * 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838)
      disease. CONCLUSION: An elevated ALT does not accurately predict significant
      liver injury. Decisions on commencing antiviral therapy should not be heavily
      based on a particular ALT threshold.

PMID- 22389716
TI  - The RNA polymerase PB2 subunit of influenza A/HongKong/156/1997 (H5N1) restricts
      the replication of reassortant ribonucleoprotein complexes [corrected].
AB  - BACKGROUND: Genetic reassortment plays a critical role in the generation of
      pandemic strains of influenza virus. The influenza virus RNA polymerase, composed
      of PB1, PB2 and PA subunits, has been suggested to influence the efficiency of
      genetic reassortment. However, the role of the RNA polymerase in the genetic
      reassortment is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      reconstituted reassortant ribonucleoprotein (RNP) complexes, and demonstrated
      that the PB2 subunit of A/HongKong/156/1997 (H5N1) [HK PB2] dramatically reduced
      the synthesis of mRNA, cRNA and vRNA when introduced into the polymerase of other
      influenza strains of H1N1 or H3N2. The HK PB2 had no significant effect on the
      assembly of the polymerase trimeric complex, or on promoter binding activity or
      replication initiation activity in vitro. However, the HK PB2 was found to
      remarkably impair the accumulation of RNP. This impaired accumulation and
      activity of RNP was fully restored when four amino acids at position 108, 508,
      524 and 627 of the HK PB2 were mutated. CONCLUSIONS/SIGNIFICANCE: Overall, we
      suggest that the PB2 subunit of influenza polymerase might play an important role
      for the replication of reassortant ribonucleoprotein complexes.

PMID- 22389717
TI  - Increasing incidence and age at diagnosis among children with type 1 diabetes
      mellitus over a 20-year period in Auckland (New Zealand).
AB  - BACKGROUND: We aimed to evaluate the incidence of type 1 diabetes mellitus in
      children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years
      (1990-2009). METHODS: We performed a retrospective review of all patients <15 yr
      diagnosed with type 1 diabetes, from an unselected complete regional cohort.
      RESULTS: There were 884 new cases of type 1 diabetes, and age at diagnosis rose
      from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r(2) = 0.31, p = 0.009). There was a
      progressive increase in type 1 diabetes incidence among children <15 yr
      (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did
      not occur evenly among age groups, being 2.5-fold higher in older children (10-14
      yr) than in the youngest group (0-4 yr). The incidence of new cases of type 1
      diabetes was highest in New Zealand Europeans throughout the study period in all
      age groups (p<0.0001), but the rate of increase was similar in New Zealand
      Europeans and Non-Europeans. Type 1 diabetes incidence and average annual
      increase were similar in both sexes. There was no change in BMI SDS shortly after
      diagnosis, and no association between BMI SDS and age at diagnosis. CONCLUSIONS:
      There has been a steady increase in type 1 diabetes incidence among children <15
      yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has
      increased and the greatest rise in incidence occurred in children 10-14 yr. There
      was little change in BMI SDS in this population, providing no support for the
      'accelerator hypothesis'.

PMID- 22389718
TI  - Adipocyte-specific protein tyrosine phosphatase 1B deletion increases
      lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.
AB  - Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and
      insulin signaling, is positively correlated with adiposity and contributes to
      insulin resistance. Global PTP1B deletion improves diet-induced obesity and
      glucose homeostasis via enhanced leptin signaling in the brain and increased
      insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes
      is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of
      adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively
      establish the role of adipocyte-PTP1B in body mass regulation and glucose
      homeostasis, adipocyte-specific-PTP1B knockout mice (adip-crePTP1B(-/-)) were
      generated using the adiponectin-promoter to drive Cre-recombinase expression.
      Chow-fed adip-crePTP1B(-/-) mice display enlarged adipocytes, despite having
      similar body weight/adiposity and glucose homeostasis compared to controls. High
      fat diet (HFD)-fed adip-crePTP1B(-/-) mice display no differences in body
      weight/adiposity but exhibit larger adipocytes, increased circulating glucose and
      leptin levels, reduced leptin sensitivity and increased basal lipogenesis
      compared to controls. This is associated with decreased insulin receptor (IR) and
      Akt/PKB phosphorylation, increased lipogenic gene expression and increased
      hypoxia-induced factor-1-alpha (Hif-1alpha) expression. Adipocyte-specific PTP1B
      deletion does not beneficially manipulate signaling pathways regulating glucose
      homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover,
      PTP1B does not appear to be the major negative regulator of the IR in adipocytes.

PMID- 22389719
TI  - Frequent heterogeneous missense mutations of GGAP2 in prostate cancer:
      implications for tumor biology, clonality and mutation analysis.
AB  - Prostate cancer is the most common visceral malignancy in Western men and a major
      cause of cancer deaths. Increased activation of the AKT and NFkB pathways have
      been identified as critical steps in prostate cancer initiation and progression.
      GGAP2 (GTP-binding and GTPase activating protein 2) is a multidomain protein that
      contains an N-terminal Ras homology domain (GTPase), followed by a PH domain, a C
      terminal GAP domain and an ankyrin repeat domain. GGAP2 can directly activate
      signaling via both the AKT and NFkB pathways and acts as a node of crosstalk
      between these pathways. Increased GGAP2 expression is present in three quarters
      of prostate cancers. Mutations of GGAP2 have been reported in cell lines from
      other malignancies. We therefore analyzed 84 prostate cancer tissues and 43
      benign prostate tissues for somatic mutations in GGAP2 by direct sequencing of
      individual clones derived from the GAP and GTPase domains of normal and tumor
      tissue. Overall, half of cancers contained mutant GAP domain clones and in 20% of
      cancers, 30% or more of clones were mutant in the GAP domain. Surprisingly, the
      mutations were heterogeneous and nonclonal, with multiple different mutations
      being present in many tumors. Similar findings were observed in the analysis of
      the GTPase domain. Mutant GGAP2 proteins had significantly higher transcriptional
      activity using AP-1 responsive reporter constructs when compared to wild-type
      protein. Furthermore, the presence of these mutations was associated with
      aggressive clinical behavior. The presence of high frequency nonclonal mutations
      of a single gene is novel and represents a new mode of genetic alteration that
      can promote tumor progression. Analysis of mutations in cancer has been used to
      predict outcome and guide therapeutic target identification but such analysis has
      focused on clonal mutations. Our studies indicate that in some cases high
      frequency nonclonal mutations may need to be assessed as well.

PMID- 22389720
TI  - Setting an optimal alpha that minimizes errors in null hypothesis significance
      tests.
AB  - Null hypothesis significance testing has been under attack in recent years,
      partly owing to the arbitrary nature of setting alpha (the decision-making
      threshold and probability of Type I error) at a constant value, usually 0.05. If
      the goal of null hypothesis testing is to present conclusions in which we have
      the highest possible confidence, then the only logical decision-making threshold
      is the value that minimizes the probability (or occasionally, cost) of making
      errors. Setting alpha to minimize the combination of Type I and Type II error at
      a critical effect size can easily be accomplished for traditional statistical
      tests by calculating the alpha associated with the minimum average of alpha and
      beta at the critical effect size. This technique also has the flexibility to
      incorporate prior probabilities of null and alternate hypotheses and/or relative
      costs of Type I and Type II errors, if known. Using an optimal alpha results in
      stronger scientific inferences because it estimates and minimizes both Type I
      errors and relevant Type II errors for a test. It also results in greater
      transparency concerning assumptions about relevant effect size(s) and the
      relative costs of Type I and II errors. By contrast, the use of alpha = 0.05
      results in arbitrary decisions about what effect sizes will likely be considered
      significant, if real, and results in arbitrary amounts of Type II error for
      meaningful potential effect sizes. We cannot identify a rationale for continuing
      to arbitrarily use alpha = 0.05 for null hypothesis significance tests in any
      field, when it is possible to determine an optimal alpha.

PMID- 22389721
TI  - Discovery and genomic characterization of noroviruses from a gastroenteritis
      outbreak in domestic cats in the US.
AB  - Norovirus (NoV) RNA was detected in the stools of 6 out 14 (42.8%) 8-12-week-old
      cats with enteritis from a feline shelter, in New York State. Upon sequence
      analysis of the complete capsid, the six NoVs were found to be identical,
      suggesting the spread of a unique NoV strain in the shelter. The full-length
      genomic sequence (7839 nt) of one feline NoV, CU081210E/2010/US, was determined.
      In the capsid protein VP1 region, the virus displayed the highest amino acid
      identity to animal genogroup IV genotype 2 (GIV.2) NoVs: lion/Pistoia-387/06/IT
      (97.9%) and dog/Bari-170/07/IT (90.4%). These findings document the discovery of
      a novel feline calicivirus, different from vesiviruses, and extend the spectrum
      of NoV host range. Epidemiological studies using feline NoV-specific diagnostic
      tools and experimental infection of cats are required to understand whether NoVs
      have a pathogenic role in this species.

PMID- 22389722
TI  - Secretion and N-linked glycosylation are required for prostatic acid phosphatase
      catalytic and antinociceptive activity.
AB  - Secretory human prostatic acid phosphatase (hPAP) is glycosylated at three
      asparagine residues (N62, N188, N301) and has potent antinociceptive effects when
      administered to mice. Currently, it is unknown if these N-linked residues are
      required for hPAP protein stability and activity in vitro or in animal models of
      chronic pain. Here, we expressed wild-type hPAP and a series of Asn to Gln point
      mutations in the yeast Pichia pastoris X33 then analyzed protein levels and
      enzyme activity in cell lysates and in conditioned media. Pichia secreted wild
      type recombinant (r)-hPAP into the media (6-7 mg protein/L). This protein was as
      active as native hPAP in biochemical assays and in mouse models of inflammatory
      pain and neuropathic pain. In contrast, the N62Q and N188Q single mutants and the
      N62Q, N188Q double mutant were expressed at lower levels and were less active
      than wild-type r-hPAP. The purified N62Q, N188Q double mutant protein was also
      1.9 fold less active in vivo. The N301Q mutant was not expressed, suggesting a
      critical role for this residue in protein stability. To explicitly test the
      importance of secretion, a construct lacking the signal peptide of hPAP was
      expressed in Pichia and assayed. This "cellular" construct was not expressed at
      levels detectable by western blotting. Taken together, these data indicate that
      secretion and post-translational carbohydrate modifications are required for PAP
      protein stability and catalytic activity. Moreover, our findings indicate that
      recombinant hPAP can be produced in Pichia--a yeast strain that is used to
      generate biologics for therapeutic purposes.

PMID- 22389723
TI  - Expression of Bcl-2 and Bax in mouse renal tubules during kidney development.
AB  - Bcl-2 and Bax play an important role in apoptosis regulation, as well as in cell
      adhesion and migration during kidney morphogenesis, which is structurally and
      functionally related to mitochondria. In order to elucidate the role of Bcl-2 and
      Bax during kidney development, it is essential to establish the exact location of
      their expression in the kidney. The present study localized their expression
      during kidney development. Kidneys from embryonic (E) 16-, 17-, 18-day-old mouse
      fetuses, and postnatal (P) 1-, 3-, 5-, 7-, 14-, 21-day-old pups were embedded in
      Epon. Semi-thin serial sections from two E17 kidneys underwent computer assisted
      3D tubule tracing. The tracing was combined with a newly developed
      immunohistochemical technique, which enables immunohistochemistry on
      glutaraldehyde fixated plastic embedded sections. Thereby, the microstructure
      could be described in detail, and the immunochemistry can be performed using
      exactly the same sections. The study showed that Bcl-2 and Bax were strongly
      expressed in mature proximal convoluted tubules at all time points, less strongly
      expressed in proximal straight tubules, and only weakly in immature proximal
      tubules and distal tubules. No expression was detected in ureteric bud and other
      earlier developing structures, such as comma bodies, S shaped bodies, glomeruli,
      etc. Tubules expressing Bcl-2 only were occasionally observed. The present study
      showed that, during kidney development, Bcl-2 and Bax are expressed differently
      in the proximal and distal tubules, although these two tubule segments are almost
      equally equipped with mitochondria. The functional significance of the different
      expression of Bcl-2 and Bax in proximal and distal tubules is unknown. However,
      the findings of the present study suggest that the mitochondrial function differs
      between mature proximal tubules and in the rest of the tubules. The function of
      Bcl-2 and Bax during tubulogenesis still needs to be investigated.

PMID- 22389724
TI  - Bone marrow-derived progenitor cells augment venous remodeling in a mouse dorsal
      skinfold chamber model.
AB  - The delivery of bone marrow-derived cells (BMDCs) has been widely used to
      stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched
      subpopulation of BMDCs that is able to augment venular remodeling, a generally
      unexplored area in microvascular research. Two populations of BMDCs, whole bone
      marrow (WBM) and Lin(-)/Sca-1(+) progenitor cells, were encapsulated in sodium
      alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation
      that encapsulated Sca-1(+) progenitor cells enhance venular remodeling, the cells
      and tissue were analyzed on structural and molecular levels. Venule walls were
      thickened and contained more nuclei after Sca-1(+) progenitor cell delivery. In
      addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif)
      ligand 2 (CXCL2) and interferon gamma (IFNgamma) that are over 5-fold higher
      compared to WBM. Tissues that received progenitors expressed significantly higher
      protein levels of vascular endothelial growth factor (VEGF), monocyte chemotactic
      protein-1 (MCP-1), and platelet derived growth factor-BB (PDGF-BB) compared to
      tissues that received an alginate control construct. Nine days following cell
      delivery, tissue from progenitor recipients contained 39% more CD45(+)
      leukocytes, suggesting that these cells may enhance venular remodeling through
      the modulation of the local immune environment. Results show that different BMDC
      populations elicit different microvascular responses. In this model, Sca-1(+)
      progenitor cell-derived CXCL2 and IFNgamma may mediate venule enlargement via
      modulation of the local inflammatory environment.

PMID- 22389725
TI  - Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed
      in community-dwelling older persons: an exploratory study.
AB  - BACKGROUND: Preclinical studies strongly suggest that accelerated apoptosis in
      skeletal myocytes may be involved in the pathogenesis of sarcopenia. However,
      evidence in humans is sparse. In the present study, we investigated whether
      apoptotic signaling in the skeletal muscle was associated with indices of muscle
      mass and function in older persons. METHODOLOGY/PRINCIPAL FINDINGS: Community
      dwelling older adults were categorized into high-functioning (HF) or low
      functioning (LF) groups according to their short physical performance battery
      (SPPB) summary score. Participants underwent an isokinetic knee extensor strength
      test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis
      muscle samples were obtained by percutaneous needle biopsy and assayed for the
      expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid
      conditions and medications as well as knee extensor strength were not different
      between groups. HF participants displayed greater thigh muscle volume compared
      with LF persons. Multivariate partial least squares (PLS) regressions showed
      significant correlations between caspase-dependent apoptotic signaling proteins
      and the muscular percentage of thigh volume (R(2) = 0.78; Q(2) = 0.61) as well as
      gait speed (R(2) = 0.81; Q(2) = 0.56). Significant variables in the PLS model of
      percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic
      cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly
      described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive
      apoptotic variables did not differ between functional groups. No correlation was
      determined between apoptotic signaling proteins and muscle strength or quality
      (strength per unit volume). CONCLUSIONS/SIGNIFICANCE: Data from this exploratory
      study show for the first time that apoptotic signaling is correlated with indices
      of muscle mass and function in a cohort of community-dwelling older persons.
      Future larger-scale studies are needed to corroborate these preliminary findings
      and determine if down-regulation of apoptotic signaling in skeletal myocytes will
      provide improvements in the muscle mass and functional status of older persons.

PMID- 22389726
TI  - Toxocariasis in Cuba: a literature review.
AB  - Human toxocariasis (HT) is a zoonotic disease caused by infection with the larval
      stage of Toxocara canis, the intestinal roundworm of dogs. Infection can be
      associated with a wide clinical spectrum varying from asymptomatic to severe
      organ injury. While the incidence of symptomatic human toxocariasis appears to be
      low, infection of the human population is widespread. In Cuba, a clear overview
      on the status of the disease is lacking. Here, we review the available
      information on toxocariasis in Cuba as a first step to estimate the importance of
      the disease in the country. Findings are discussed and put in a broader
      perspective. Data gaps are identified and suggestions on how to address these are
      presented. The available country data suggest that Toxocara infection of the
      definitive dog host and environmental contamination with Toxocara spp. eggs is
      substantial, but information on HT is less conclusive. The availability of
      adequate diagnostic tools in the country should be guaranteed. Dedicated studies
      are needed for a reliable assessment of the impact of toxocariasis in Cuba and
      the design of prevention or control strategies.

PMID- 22389727
TI  - The blueprint for rabies prevention and control: a novel operational toolkit for
      rabies elimination.

PMID- 22389728
TI  - Improving access to medicines for neglected tropical diseases in developing
      countries: lessons from three emerging economies.

PMID- 22389729
TI  - Neglected tropical diseases of the Middle East and North Africa: review of their
      prevalence, distribution, and opportunities for control.
AB  - The neglected tropical diseases (NTDs) are highly endemic but patchily
      distributed among the 20 countries and almost 400 million people of the Middle
      East and North Africa (MENA) region, and disproportionately affect an estimated
      65 million people living on less than US$2 per day. Egypt has the largest number
      of people living in poverty of any MENA nation, while Yemen has the highest
      prevalence of people living in poverty. These two nations stand out for having
      suffered the highest rates of many NTDs, including the soil-transmitted nematode
      infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and
      trachoma, although they should be recognized for recent measures aimed at NTD
      control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria,
      Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic
      (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in
      MENA in rural arid regions and urban regions, respectively. Other endemic
      zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis.
      Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma
      hemorrhagic fever have also emerged. Great strides have been made towards
      elimination of several endemic NTDs, including lymphatic filariasis in Egypt and
      Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco,
      Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates.
      A particularly noteworthy achievement is the long battle waged against
      schistosomiasis in Egypt, where prevalence has been brought down by regular
      praziquantel treatment. Conflict and human and animal migrations are key social
      determinants in preventing the control or elimination of NTDs in the MENA, while
      local political will, strengthened international and intersectoral cooperative
      efforts for surveillance, mass drug administration, and vaccination are essential
      for elimination.

PMID- 22389730
TI  - Genetic characterization of Zika virus strains: geographic expansion of the Asian
      lineage.
AB  - BACKGROUND: Zika virus (ZIKV) is a mosquito-borne flavivirus distributed
      throughout much of Africa and Asia. Infection with the virus may cause acute
      febrile illness that clinically resembles dengue fever. A recent study indicated
      the existence of three geographically distinct viral lineages; however this
      analysis utilized only a single viral gene. Although ZIKV has been known to
      circulate in both Africa and Asia since at least the 1950s, little is known about
      the genetic relationships between geographically distinct virus strains.
      Moreover, the geographic origin of the strains responsible for the epidemic that
      occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010
      pediatric case in Cambodia, has not been determined. METHODOLOGY/PRINCIPAL
      FINDINGS: To elucidate the genetic relationships of geographically distinct ZIKV
      strains and the origin of the strains responsible for the 2007 outbreak on Yap
      Island and a 2010 Cambodian pediatric case of ZIKV infection, the nucleotide
      sequences of the open reading frame of five isolates from Cambodia, Malaysia,
      Nigeria, Uganda, and Senegal collected between 1947 and 2010 were determined.
      Phylogenetic analyses of these and previously published ZIKV sequences revealed
      the existence of two main virus lineages (African and Asian) and that the strain
      responsible for the Yap epidemic and the Cambodian case most likely originated in
      Southeast Asia. Examination of the nucleotide and amino acid sequence alignments
      revealed the loss of a potential glycosylation site in some of the virus strains,
      which may correlate with the passage history of the virus.
      CONCLUSIONS/SIGNIFICANCE: The basal position of the ZIKV strain isolated in
      Malaysia in 1966 suggests that the recent outbreak in Micronesia was initiated by
      a strain from Southeast Asia. Because ZIKV infection in humans produces an
      illness clinically similar to dengue fever and many other tropical infectious
      diseases, it is likely greatly misdiagnosed and underreported.

PMID- 22389731
TI  - Development and characterization of a reverse genetic system for studying dengue
      virus serotype 3 strain variation and neutralization.
AB  - Dengue viruses (DENV) are enveloped single-stranded positive-sense RNA viruses
      transmitted by Aedes spp. mosquitoes. There are four genetically distinct
      serotypes designated DENV-1 through DENV-4, each further subdivided into distinct
      genotypes. The dengue scientific community has long contended that infection with
      one serotype confers lifelong protection against subsequent infection with the
      same serotype, irrespective of virus genotype. However this hypothesis is under
      increased scrutiny and the role of DENV genotypic variation in protection from
      repeated infection is less certain. As dengue vaccine trials move increasingly
      into field-testing, there is an urgent need to develop tools to better define the
      role of genotypic variation in DENV infection and immunity. To better understand
      genotypic variation in DENV-3 neutralization and protection, we designed and
      constructed a panel of isogenic, recombinant DENV-3 infectious clones, each
      expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines
      1982 (genotype I), Thailand 1995 (genotype II), Sri Lanka 1989 and Cuba 2002
      (genotype III) and Puerto Rico 1977 (genotype IV). We used the panel to explore
      how natural envelope variation influences DENV-polyclonal serum interactions.
      When the recombinant viruses were tested in neutralization assays using immune
      sera from primary DENV infections, neutralization titers varied by as much as ~19
      fold, depending on the expressed envelope glycoprotein. The observed variability
      in neutralization titers suggests that relatively few residue changes in the E
      glycoprotein may have significant effects on DENV specific humoral immunity and
      influence antibody mediated protection or disease enhancement in the setting of
      both natural infection and vaccination. These genotypic differences are also
      likely to be important in temporal and spatial microevolution of DENV-3 in the
      background of heterotypic neutralization. The recombinant and synthetic tools
      described here are valuable for testing hypotheses on genetic determinants of
      DENV-3 immunopathogenesis.

PMID- 22389732
TI  - The transcriptome analysis of Strongyloides stercoralis L3i larvae reveals
      targets for intervention in a neglected disease.
AB  - BACKGROUND: Strongyloidiasis is one of the most neglected diseases distributed
      worldwide with endemic areas in developed countries, where chronic infections are
      life threatening. Despite its impact, very little is known about the molecular
      biology of the parasite involved and its interplay with its hosts. Next
      generation sequencing technologies now provide unique opportunities to rapidly
      address these questions. PRINCIPAL FINDINGS: Here we present the first
      transcriptome of the third larval stage of S. stercoralis using 454 sequencing
      coupled with semi-automated bioinformatic analyses. 253,266 raw sequence reads
      were assembled into 11,250 contiguous sequences, most of which were novel. 8037
      putative proteins were characterized based on homology, gene ontology and/or
      biochemical pathways. Comparison of the transcriptome of S. strongyloides with
      those of other nematodes, including S. ratti, revealed similarities in
      transcription of molecules inferred to have key roles in parasite-host
      interactions. Enzymatic proteins, like kinases and proteases, were abundant. 1213
      putative excretory/secretory proteins were compiled using a new pipeline which
      included non-classical secretory proteins. Potential drug targets were also
      identified. CONCLUSIONS: Overall, the present dataset should provide a solid
      foundation for future fundamental genomic, proteomic and metabolomic explorations
      of S. stercoralis, as well as a basis for applied outcomes, such as the
      development of novel methods of intervention against this neglected parasite.

PMID- 22389733
TI  - Molecular mechanisms of drug resistance in natural Leishmania populations vary
      with genetic background.
AB  - The evolution of drug-resistance in pathogens is a major global health threat.
      Elucidating the molecular basis of pathogen drug-resistance has been the focus of
      many studies but rarely is it known whether a drug-resistance mechanism
      identified is universal for the studied pathogen; it has seldom been clarified
      whether drug-resistance mechanisms vary with the pathogen's genotype.
      Nevertheless this is of critical importance in gaining an understanding of the
      complexity of this global threat and in underpinning epidemiological surveillance
      of pathogen drug resistance in the field. This study aimed to assess the
      molecular and phenotypic heterogeneity that emerges in natural parasite
      populations under drug treatment pressure. We studied lines of the protozoan
      parasite Leishmania (L.) donovani with differential susceptibility to antimonial
      drugs; the lines being derived from clinical isolates belonging to two distinct
      genetic populations that circulate in the leishmaniasis endemic region of Nepal.
      Parasite pathways known to be affected by antimonial drugs were characterised on
      five experimental levels in the lines of the two populations. Characterisation of
      DNA sequence, gene expression, protein expression and thiol levels revealed a
      number of molecular features that mark antimonial-resistant parasites in only one
      of the two populations studied. A final series of in vitro stress phenotyping
      experiments confirmed this heterogeneity amongst drug-resistant parasites from
      the two populations. These data provide evidence that the molecular changes
      associated with antimonial-resistance in natural Leishmania populations depend on
      the genetic background of the Leishmania population, which has resulted in a
      divergent set of resistance markers in the Leishmania populations. This
      heterogeneity of parasite adaptations provides severe challenges for the control
      of drug resistance in the field and the design of molecular surveillance tools
      for widespread applicability.

PMID- 22389734
TI  - Therapeutic DNA vaccine encoding peptide P10 against experimental
      paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the
      most prevalent invasive fungal disease in South America. Systemic mycoses are the
      10th most common cause of death among infectious diseases in Brazil and PCM is
      responsible for more than 50% of deaths due to fungal infections. PCM is
      typically treated with sulfonamides, amphotericin B or azoles, although complete
      eradication of the fungus may not occur and relapsing disease is frequently
      reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can
      induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm
      and experimental data have confirmed that most HLA-DR molecules can present P10,
      which suggests that P10 is a candidate antigen for a PCM vaccine. In the current
      work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12
      inserts was tested in murine models of PCM. When given prior to or after
      infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with
      P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of
      infected mice. In fact, intramuscular administration of a combination of plasmids
      expressing P10 and IL-12 given weekly for one month, followed by single
      injections every month for 3 months restored normal lung architecture and
      eradicated the fungus in mice that were infected one month prior to treatment.
      The data indicate that immunization with these plasmids is a powerful procedure
      for prevention and treatment of experimental PCM, with the perspective of being
      also effective in human patients.

PMID- 22389735
TI  - Dengue infection in children in Ratchaburi, Thailand: a cohort study. II.
      Clinical manifestations.
AB  - BACKGROUND: Dengue infection is one of the most important mosquito-borne
      diseases. More data regarding the disease burden and the prevalence of each
      clinical spectrum among symptomatic infections and the clinical manifestations
      are needed. This study aims to describe the incidence and clinical manifestations
      of symptomatic dengue infection in Thai children during 2006 through 2008. STUDY
      DESIGN: This study is a school-based prospective open cohort study with a 9,448
      person-year follow-up in children aged 3-14 years. Active surveillance for
      febrile illnesses was done in the studied subjects. Subjects who had febrile
      illness were asked to visit the study hospital for clinical and laboratory
      evaluation, treatment, and serological tests for dengue infection. The clinical
      data from medical records, diary cards, and data collection forms were collected
      and analyzed. RESULTS: Dengue infections were the causes of 12.1% of febrile
      illnesses attending the hospital, including undifferentiated fever (UF) (49.8%),
      dengue fever (DF) (39.3%) and dengue hemorrhagic fever (DHF) (10.9%). Headache,
      anorexia, nausea/vomiting and myalgia were common symptoms occurring in more than
      half of the patients. The more severe dengue spectrum (i.e., DHF) had higher
      temperature, higher prevalence of nausea/vomiting, abdominal pain, rash,
      diarrhea, petechiae, hepatomegaly and lower platelet count. DHF cases also had
      significantly higher prevalence of anorexia, nausea/vomiting and abdominal pain
      during day 3-6 and diarrhea during day 4-6 of illness. The absence of
      nausea/vomiting, abdominal pain, diarrhea, petechiae, hepatomegaly and positive
      tourniquet test may predict non-DHF. CONCLUSION: Among symptomatic dengue
      infection, UF is most common followed by DF and DHF. Some clinical manifestations
      may be useful to predict the more severe disease (i.e., DHF). This study presents
      additional information in the clinical spectra of symptomatic dengue infection.

PMID- 22389736
TI  - A novel G protein-coupled receptor of Schistosoma mansoni (SmGPR-3) is activated
      by dopamine and is widely expressed in the nervous system.
AB  - Schistosomes have a well developed nervous system that coordinates virtually
      every activity of the parasite and therefore is considered to be a promising
      target for chemotherapeutic intervention. Neurotransmitter receptors, in
      particular those involved in neuromuscular control, are proven drug targets in
      other helminths but very few of these receptors have been identified in
      schistosomes and little is known about their roles in the biology of the worm.
      Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named
      SmGPR-3) that was cloned, expressed heterologously and shown to be activated by
      dopamine, a well established neurotransmitter of the schistosome nervous system.
      SmGPR-3 belongs to a new clade of "orphan" amine-like receptors that exist in
      schistosomes but not the mammalian host. Further analysis of the recombinant
      protein showed that SmGPR-3 can also be activated by other catecholamines,
      including the dopamine metabolite, epinine, and it has an unusual antagonist
      profile when compared to mammalian receptors. Confocal immunofluorescence
      experiments using a specific peptide antibody showed that SmGPR-3 is abundantly
      expressed in the nervous system of schistosomes, particularly in the main nerve
      cords and the peripheral innervation of the body wall muscles. In addition, we
      show that dopamine, epinine and other dopaminergic agents have strong effects on
      the motility of larval schistosomes in culture. Together, the results suggest
      that SmGPR-3 is an important neuronal receptor and is probably involved in the
      control of motor activity in schistosomes. We have conducted a first analysis of
      the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking
      simulations. This investigation has identified potentially important differences
      between SmGPR-3 and host dopamine receptors that could be exploited to develop
      new, parasite-selective anti-schistosomal drugs.

PMID- 22389737
TI  - Regulation of global gene expression in human Loa loa infection is a function of
      chronicity.
AB  - BACKGROUND: Human filarial infection is characterized by downregulated parasite
      antigen specific T cell responses but distinct differences exist between patients
      with longstanding infection (endemics) and those who acquired infection through
      temporary residency or visits to filarial-endemic regions (expatriates). METHODS
      AND FINDINGS: To characterize mechanisms underlying differences in T cells,
      analysis of global gene expression using human spotted microarrays was conducted
      on CD4(+) and CD8(+) T cells from microfilaremic Loa loa-infected endemic and
      expatriate patients. Assessment of unstimulated cells showed overexpression of
      genes linked to inflammation and caspase-associated cell death, particularly in
      endemics, and enrichment of the Th1/Th2 canonical pathway in endemic CD4(+)
      cells. However, pathways within CD8(+) unstimulated cells were most significantly
      enriched in both patient groups. Antigen (Ag)-driven gene expression was assessed
      to microfilarial Ag (MfAg) and to the nonparasite Ag streptolysin O (SLO). For
      MfAg-driven cells, the number of genes differing significantly from unstimulated
      cells was greater in endemics compared to expatriates (p<0.0001). Functional
      analysis showed a differential increase in genes associated with NFkB (both
      groups) and caspase activation (endemics). While the expatriate response to MfAg
      was primarily a CD4(+) pro-inflammatory one, the endemic response included CD4(+)
      and CD8(+) cells and was linked to insulin signaling, histone complexes, and
      ubiquitination. Unlike the enrichment of canonical pathways in CD8(+)
      unstimulated cells, both groups showed pathway enrichment in CD4(+) cells to
      MfAg. Contrasting with the divergent responses to MfAg seen between endemics and
      expatriates, the CD4(+) response to SLO was similar; however, CD8(+) cells
      differed strongly in the nature and numbers (156 [endemics] vs 36 [expatriates])
      of genes with differential expression. CONCLUSIONS: These data suggest several
      important pathways are responsible for the different outcomes seen among filarial
      infected patients with varying levels of chronicity and imply an important role
      for CD8(+) cells in some of the global changes seen with lifelong exposure.

PMID- 22389738
TI  - Chemotactic and inflammatory responses in the liver and brain are associated with
      pathogenesis of Rift Valley fever virus infection in the mouse.
AB  - Rift Valley fever virus (RVFV) is a major human and animal pathogen associated
      with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic
      to parts of Africa and the Arabian Peninsula, but there is significant concern
      regarding its introduction into non-endemic regions and the potentially
      devastating effect to livestock populations with concurrent infections of humans.
      To date, there is little detailed data directly comparing the host response to
      infection with wild-type or vaccine strains of RVFV and correlation with viral
      pathogenesis. Here we characterized clinical and systemic immune responses to
      infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6
      mouse. Animals infected with live-attenuated MP-12 survived productive viral
      infection with little evidence of clinical disease and minimal cytokine response
      in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion
      of lymphocytes and platelets and elicited a strong, systemic cytokine response
      which correlated with high virus titers and significant tissue pathology.
      Lymphopenia and platelet depletion were indicators of disease onset with
      indications of lymphocyte recovery correlating with increases in G-CSF
      production. RVFV is hepatotropic and in these studies significant clinical and
      histological data supported these findings; however, significant evidence of a
      pro-inflammatory response in the liver was not apparent. Rather, viral infection
      resulted in a chemokine response indicating infiltration of immunoreactive cells,
      such as neutrophils, which was supported by histological data. In brains of ZH501
      infected mice, a significant chemokine and pro-inflammatory cytokine response was
      evident, but with little pathology indicating meningoencephalitis. These data
      suggest that RVFV pathogenesis in mice is associated with a loss of liver
      function due to liver necrosis and hepatitis yet the long-term course of disease
      for those that might survive the initial hepatitis is neurologic in nature which
      is supported by observations of human disease and the BALB/c mouse model.

PMID- 22389739
TI  - High-resolution melting (HRM) of the cytochrome B gene: a powerful approach to
      identify blood-meal sources in Chagas disease Vectors.
AB  - Methods to determine blood-meal sources of hematophagous Triatominae bugs (Chagas
      disease vectors) are serological or based on PCR employing species-specific
      primers or heteroduplex analysis, but these are expensive, inaccurate, or
      problematic when the insect has fed on more than one species. To solve those
      problems, we developed a technique based on HRM analysis of the mitochondrial
      gene cytochrome B (Cyt b). This technique recognized 14 species involved in
      several ecoepidemiological cycles of the transmission of Trypanosoma cruzi and it
      was suitable with DNA extracted from intestinal content and feces 30 days after
      feeding, revealing a resolution power that can display mixed feedings. Field
      samples were analyzed showing blood meal sources corresponding to domestic,
      peridomiciliary and sylvatic cycles. The technique only requires a single pair of
      primers that amplify the Cyt b gene in vertebrates and no other standardization,
      making it quick, easy, relatively inexpensive, and highly accurate.

PMID- 22389740
TI  - Premolis semirufa (Walker, 1856) envenomation, disease affecting rubber tappers
      of the Amazon: searching for caterpillar-bristles toxic components.
AB  - BACKGROUND: The caterpillar of the moth Premolis semirufa (Lepidoptera:
      Arctiidae), commonly named Pararama, is endemic of the Amazon basin. Accidental
      contact with these caterpillar bristles causes local symptoms such as intense
      heat, pain, edema and itching which last for three to seven days; however, after
      multiples contacts, it may induce joint-space narrowing and bone alteration, as
      well as degeneration of the articular cartilage and immobilization of the
      affected joints. Specific treatment for this disease does not exist, but
      corticosteroids are frequently administered. Despite of the public health hazard
      of Premolis semirufa caterpillar poisoning, little is known about the nature of
      the toxic components involved in the induction of the pathology.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we have investigated the biological and
      immunochemical characteristics of the caterpillar's bristles components. Analysis
      of the bristles extract in in vitro assays revealed the presence of proteolytic
      and hyaluronidase activities but no phospholipase A(2) activity. In vivo, it was
      observed that the bristles extract is not lethal but can induce an intense
      inflammatory process, characterized by the presence of neutrophils in the paw
      tissues of injected mice. Furthermore, the bristles components stimulated an
      intense and specific antibody response but autoantibodies such as anti-DNA or
      anti-collagen type II were not detected. CONCLUSION: The results suggest that
      Premolis semirufa caterpillar bristles secretion contains a mixture of different
      enzymes that may act together in the generation and development of the clinical
      manifestations of the Pararama envenomation. Moreover, the high immunogenicity of
      the caterpillar bristles components, as shown by the generation of high antibody
      titers, may also contribute to the induction and establishment of the
      inflammatory disease.

PMID- 22389741
TI  - Dengue virus infection-enhancing activity in serum samples with neutralizing
      activity as determined by using FcgammaR-expressing cells.
AB  - BACKGROUND: Progress in dengue vaccine development has been hampered by limited
      understanding of protective immunity against dengue virus infection. Conventional
      neutralizing antibody titration assays that use FcgammaR-negative cells do not
      consider possible infection-enhancement activity. We reasoned that as FcgammaR
      expressing cells are the major target cells of dengue virus, neutralizing
      antibody titration assays using FcgammaR-expressing cells that determine the sum
      of neutralizing and infection-enhancing activity, may better reflect the
      biological properties of antibodies in vivo. METHODS AND FINDINGS: We evaluated
      serum samples from 80 residents of a dengue endemic country, Malaysia, for
      neutralizing activity, and infection-enhancing activity at 1?10 serum dilution by
      using FcgammaR-negative BHK cells and FcgammaR-expressing BHK cells. The serum
      samples consisted of a panel of patients with acute DENV infection (31%, 25/80)
      and a panel of donors without acute DENV infection (69%, 55/80). A high
      proportion of the tested serum samples (75%, 60/80) demonstrated DENV
      neutralizing activity (PRNT(50)>=10) and infection-enhancing activity. Eleven of
      18 serum samples from patients with acute secondary DENV infection demonstrated
      neutralizing activity to the infecting serotype determined by using FcgammaR
      negative BHK cells (PRNT(50)>=10), but not when determined by using FcgammaR
      expressing cells. CONCLUSION: Human serum samples with low neutralizing activity
      determined by using FcgammaR-negative cells showed DENV infection-enhancing
      activity using FcgammaR-expressing cells, whereas those with high neutralizing
      activity determined by using FcgammaR-negative cells demonstrate low or no
      infection-enhancing activity using FcgammaR-expressing cells. The results suggest
      an inverse relationship between neutralizing antibody titer and infection
      enhancing activity, and that neutralizing activity determined by using FcgammaR
      expressing cells, and not the activity determined by using FcgammaR-negative
      cells, may better reflect protection to DENV infection in vivo.

PMID- 22389742
TI  - Predictive models for the diagnostic of human visceral leishmaniasis in Brazil.
AB  - BACKGROUND AND OBJECTIVES: In Brazil, as in many other affected countries, a
      large proportion of visceral leishmaniasis (VL) occurs in remote locations and
      treatment is often performed on basis of clinical suspicion. This study aimed at
      developing predictive models to help with the clinical management of VL in
      patients with suggestive clinical of disease. METHODS: Cases of VL (n = 213) had
      the diagnosis confirmed by parasitological method, non-cases (n = 119) presented
      suggestive clinical presentation of VL but a negative parasitological diagnosis
      and a firm diagnosis of another disease. The original data set was divided into
      two samples for generation and validation of the prediction models. Prediction
      models based on clinical signs and symptoms, results of laboratory exams and
      results of five different serological tests, were developed by means of logistic
      regression and classification and regression trees (CART). From these models,
      clinical-laboratory and diagnostic prediction scores were generated. The area
      under the receiver operator characteristic curve, sensitivity, specificity, and
      positive predictive value were used to evaluate the models' performance. RESULTS:
      Based on the variables splenomegaly, presence of cough and leukopenia and on the
      results of five serological tests it was possible to generate six predictive
      models using logistic regression, showing sensitivity ranging from 90.1 to 99.0%
      and specificity ranging from 53.0 to 97.2%. Based on the variables splenomegaly,
      leukopenia, cough, age and weight loss and on the results of five serological
      tests six predictive models were generated using CART with sensitivity ranging
      from 90.1 to 97.2% and specificity ranging from 68.4 to 97.4%. The models
      composed of clinical-laboratory variables and the rk39 rapid test showed the best
      performance. CONCLUSION: The predictive models showed to be a potential useful
      tool to assist healthcare systems and control programs in their strategical
      choices, contributing to more efficient and more rational allocation of
      healthcare resources.

PMID- 22389743
TI  - Glycoinositolphospholipids from Leishmania braziliensis and L. infantum:
      modulation of innate immune system and variations in carbohydrate structure.
AB  - The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune
      response has been extensively reported. However, information about the role of
      the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with
      respect to the New World species of Leishmania. GIPLs are low molecular weight
      molecules covering the parasite surface and are similar to LPG in sharing a
      common lipid backbone and a glycan motif containing up to 7 sugars. Critical
      aspects of their structure and functions are still obscure in the interaction
      with the vertebrate host. In this study, we evaluated the role of those molecules
      in two medically important South American species Leishmania infantum and L.
      braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL),
      respectively. GIPLs derived from both species did not induce NO or TNF-alpha
      production by non-primed murine macrophages. Additionally, primed macrophages
      from mice (BALB/c, C57BL/6, TLR2-/- and TLR4-/-) exposed to GIPLs from both
      species, with exception to TNF-alpha, did not produce any of the cytokines
      analyzed (IL1-beta, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-gamma) or p38
      activation. GIPLs induced the production of TNF-alpha and NO by C57BL/6 mice,
      primarily via TLR4. Pre incubation of macrophages with GIPLs reduced
      significantly the amount of NO and IL-12 in the presence of IFN-gamma or
      lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs.
      This inhibition was reversed after PI-specific phospholipase C treatment. A
      structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs,
      suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich
      GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in
      the structure and composition of GIPLs from L. braziliensis and L. infantum.
      Also, GIPLs are important inhibitory molecules during the interaction with
      macrophages.

PMID- 22389744
TI  - The genome of Mycobacterium africanum West African 2 reveals a lineage-specific
      locus and genome erosion common to the M. tuberculosis complex.
AB  - BACKGROUND: M. africanum West African 2 constitutes an ancient lineage of the M.
      tuberculosis complex that commonly causes human tuberculosis in West Africa and
      has an attenuated phenotype relative to M. tuberculosis. METHODOLOGY/PRINCIPAL
      FINDINGS: In search of candidate genes underlying these differences, the genome
      of M. africanum West African 2 was sequenced using classical capillary sequencing
      techniques. Our findings reveal a unique sequence, RD900, that was independently
      lost during the evolution of two important lineages within the complex: the
      "modern" M. tuberculosis group and the lineage leading to M. bovis. Closely
      related to M. bovis and other animal strains within the M. tuberculosis complex,
      M. africanum West African 2 shares an abundance of pseudogenes with M. bovis but
      also with M. africanum West African clade 1. Comparison with other strains of the
      M. tuberculosis complex revealed pseudogenes events in all the known lineages
      pointing toward ongoing genome erosion likely due to increased genetic drift and
      relaxed selection linked to serial transmission-bottlenecks and an intracellular
      lifestyle. CONCLUSIONS/SIGNIFICANCE: The genomic differences identified between
      M. africanum West African 2 and the other strains of the Mycobacterium
      tuberculosis complex may explain its attenuated phenotype, and pave the way for
      targeted experiments to elucidate the phenotypic characteristic of M. africanum.
      Moreover, availability of the whole genome data allows for verification of
      conservation of targets used for the next generation of diagnostics and vaccines,
      in order to ensure similar efficacy in West Africa.

PMID- 22389745
TI  - Biochemical, mutational and in silico structural evidence for a functional
      dimeric form of the ornithine decarboxylase from Entamoeba histolytica.
AB  - BACKGROUND: Entamoeba histolytica is responsible for causing amoebiasis.
      Polyamine biosynthesis pathway enzymes are potential drug targets in parasitic
      protozoan diseases. The first and rate-limiting step of this pathway is catalyzed
      by ornithine decarboxylase (ODC). ODC enzyme functions as an obligate dimer.
      However, partially purified ODC from E. histolytica (EhODC) is reported to exist
      in a pentameric state. METHODOLOGY AND RESULTS: In present study, the oligomeric
      state of EhODC was re-investigated. The enzyme was over-expressed in Escherichia
      coli and purified. Pure protein was used for determination of secondary structure
      content using circular dichroism spectroscopy. The percentages of alpha-helix,
      beta-sheets and random coils in EhODC were estimated to be 39%, 25% and 36%
      respectively. Size-exclusion chromatography and mass spectrophotometry analysis
      revealed that EhODC enzyme exists in dimeric form. Further, computational model
      of EhODC dimer was generated. The homodimer contains two separate active sites at
      the dimer interface with Lys57 and Cys334 residues of opposite monomers
      contributing to each active site. Molecular dynamic simulations were performed
      and the dimeric structure was found to be very stable with RMSD value ~0.327 nm.
      To gain insight into the functional role, the interface residues critical for
      dimerization and active site formation were identified and mutated. Mutation of
      Lys57Ala or Cys334Ala completely abolished enzyme activity. Interestingly,
      partial restoration of the enzyme activity was observed when inactive Lys57Ala
      and Cys334Ala mutants were mixed confirming that the dimer is the active form.
      Furthermore, Gly361Tyr and Lys157Ala mutations at the dimer interface were found
      to abolish the enzyme activity and destabilize the dimer. CONCLUSION: To our
      knowledge, this is the first report which demonstrates that EhODC is functional
      in the dimeric form. These findings and availability of 3D structure model of
      EhODC dimer opens up possibilities for alternate enzyme inhibition strategies by
      targeting the dimer disruption.

PMID- 22389746
TI  - Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome(IRIS):
      Pathogenesis and Its Clinical Implications.
AB  - This review provides an overview of Cryptococcus neoformans immunology and
      focuses on the pathogenesis of Cryptococcus-related paradoxical immune
      reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases:
      (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid
      (CSF) inflammation and defects in antigen clearance; (2) during initial ART
      immune recovery, with pro-inflammatory signaling by antigen-presenting cells
      without an effector response; and (3) at IRIS, a cytokine storm with a
      predominant type-1 helper T-cell (Th(1)) interferon-gamma (IFN-gamma) response.
      Understanding IRIS pathogenesis allows for risk stratification and customization
      of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing
      microbiologic clearance by use of adjunctive agents in combination with
      amphotericin, prolonging initial induction therapy, and/or increasing the initial
      consolidation antifungal therapy dose to at least 800 mg of fluconazole daily
      until the 2-week CSF culture is known to be sterile. Prophylactic anti
      inflammatory therapies or undue delay of ART initiation in an attempt to prevent
      IRIS is unwarranted and may be dangerous.

PMID- 22389747
TI  - Adventitious bursae underlying chronic wounds: another possible deterrent to
      healing.
AB  - Adventitious bursae typically develop in areas of chronic frictional irritation,
      usually under bony prominences. Although adventitious bursae are generally well
      understood, there is a paucity of data on effects of bursae underlying chronic
      wounds in neuropathic patients. This manuscripts reviews 4 clinical cases, each
      with a neuropathic patient with adventitious bursae underlying chronic nonhealing
      wound and strategies for treatment.

PMID- 22389748
TI  - Long-term survival and serial assessment of stroke damage and recovery -
      practical and methodological considerations.
AB  - Impairments caused by stroke remain the main cause for adult disability. Despite
      a vigorous research effort, only 1 thrombolytic treatment has been approved in
      acute stroke (<3h). The limitations of preclinical studies and how these can be
      overcome have been the subject of various guidelines. However, often these
      guidelines focus on the acute stroke setting and omit long-term outcome measures,
      such as behaviour and neuroimaging. The considerations and practicalities of
      including the serial assessment of these approaches and their significance to
      establish therapeutic efficacy are discussed here.

PMID- 22389749
TI  - Molecular and Pathophysiological Features of Angiotensinogen: A Mini Review.
AB  - The renin-angiotensin system is an essential regulatory system for blood pressure
      and fluid homeostasis. Angiotensinogen is the only known precursor of all the
      peptides generated in this system. While many of the basic understandings of
      angiotensinogen have come from research efforts to define its role in blood
      pressure regulation, novel pathophysiological functions of angiotensinogen have
      been discovered in the last two decades including kidney developmental
      abnormalities, atherosclerosis, and obesity. Despite the impressive advance in
      the understanding of angiotensinogen gene structure and protein functions, some
      fundamental questions remain unanswered. In this short review, we provide
      contemporary insights into the molecular characteristics of angiotensinogen and
      its pathophysiological features. In light of the recent progress, we emphasize
      some newly recognized functional features of angiotensinogen other than its
      regulation on blood pressure.

PMID- 22389750
TI  - Azido Homoalanine is a Useful Infrared Probe for Monitoring Local
      Electrostatistics and Sidechain Solvation in Proteins.
AB  - The use of IR probes to monitor protein structure, deduce local electric field,
      and investigate the mechanism of enzyme catalysis and protein folding has
      attracted increasing attention. Here, the azidohomoalanine (Aha) is considered as
      a useful IR probe. The intricate details of the distinct effects of backbone
      peptide bonds and H-bonded water molecules on the azido stretch mode of the IR
      probe Aha were revealed by carrying out QM/MM MD simulations of two variants of
      the protein NTL9, NTL9-Met1Aha and NTL9-Ile4Aha and comparing the resulting
      simulated IR spectra with experiments.

PMID- 22389752
TI  - Molecular typing in public health laboratories: from an academic indulgence to an
      infection control imperative.
AB  - Using three Austrian case studies, the variegated applications of molecular
      typing in today's public health laboratories are discussed to help illustrate
      preventive management strategies relying on DNA subtyping. DNA macrorestriction
      analysis by pulsed field gel electrophoresis has become the gold standard for
      subtyping of food borne pathogens like listeria, salmonella, campylobacter and
      Bacillus cereus. Using a Salmonella Mbandaka outbreak from the year 2010 as
      example, it is shown how the comparison of patterns from human isolates, food
      isolates, animal isolates and feed isolates can allow to identify and confirm a
      source of disease. An epidemiological connection between the simultaneous
      occurrence of tuberculosis in cattle and deer with cases of human tuberculosis
      due to Mycobacterium caprae in 2010 was excluded using mycobacterial interspersed
      repetitive units variable-number tandem repeats subtyping. Also in 2010,
      multilocus sequence typing with nonselective housekeeping genes, the so-called
      sequence based typing protocol, was used to elucidate connections between an
      environmental source (a hospital drinking water system) and a case of
      legionellosis. During the last decades, molecular typing has evolved to become a
      routine tool in the daily work of public health laboratories. The challenge is
      now no longer to simply type microorganisms, but to type them in a way that
      allows for data exchange between public health laboratories all over the world.

PMID- 22389751
TI  - Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the
      Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease.
AB  - The neurotransmitter dopamine plays important roles in modulating cognitive,
      affective, and motor functions. Dysregulation of dopaminergic neurotransmission
      is thought to be involved in the pathophysiology of several psychiatric and
      neurological disorders, including schizophrenia, Parkinson's disease and drug
      abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic,
      input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine
      receptor-mediated pathways as potential targets for the treatment of these
      disorders classically viewed as "dopamine based". There are five known muscarinic
      receptor subtypes (M(1) to M(5)). Due to their overlapping expression patterns
      and the lack of receptor subtype-specific ligands, the roles of the individual
      muscarinic receptors have long remained elusive. During the past decade, studies
      with knock-out mice lacking specific muscarinic receptor subtypes have greatly
      advanced our knowledge of the physiological roles of the M(1)-M(5) receptors.
      Recently, new ligands have been developed that can interact with allosteric sites
      on different muscarinic receptor subtypes, rather than the conventional
      (orthosteric) acetylcholine binding site. Such agents may lead to the development
      of novel classes of drugs useful for the treatment of psychosis, drug abuse and
      Parkinson's disease. The present review highlights recent studies carried out
      using muscarinic receptor knock-out mice and new subtype-selective allosteric
      ligands to assess the roles of M(1), M(4), and M(5) receptors in various central
      processes that are under strong dopaminergic control. The outcome of these
      studies opens new perspectives for the use of novel muscarinic drugs for several
      severe disorders of the CNS.

PMID- 22389753
TI  - Trend of mortality rate and injury burden of transport accidents, suicides, and
      falls.
AB  - OBJECTIVES: Recently injury has become a major world-wide health problem. But
      studies in Korea about injuries were very few. Thus, this study was conducted to
      analyze the trend of major injuries from 1991 to 2006 and to provide basic data
      for preventing injuries. METHODS: This study was based on the National
      Statistical Office data from 1991 to 2006 and calculated to estimate the burden
      of major injuries by using the standard expected years of life lost (SEYLL) and
      total lost earnings equation. RESULTS: For transport accidents, mortality, SEYLL
      and total lost earnings were increased from 1991 to 1996 and decreased from 2000
      to 2006. On the other hand, for suicides, these were increased gradually. Since
      2003, falls were included in ten leading causes of death. This study showed that
      injury causes major social and economical losses. CONCLUSIONS: We could reduce
      injury related premature death through active interest in injury prevention
      program.

PMID- 22389754
TI  - Impact of individual and combined health behaviors on all causes of premature
      mortality among middle aged men in Korea: the Seoul Male Cohort Study.
AB  - OBJECTIVES: The aim of this study was to evaluate and quantify the risk of both
      individual and combined health behaviors on premature mortality in middle aged
      men in Korea. METHODS: In total, 14 533 male subjects 40 to 59 years of age were
      recruited. At enrollment, subjects completed a baseline questionnaire, which
      included information about socio-demographic factors, past medical history, and
      life style. During the follow-up period from 1993 to 2008, we identified 990 all
      cause premature deaths using national death certificates. A Cox proportional
      hazard regression model was used to estimate the hazard ratio (HR) of each health
      risk behavior, which included smoking, drinking, physical inactivity, and lack of
      sleep hours. Using the Cox model, each health behavior was assigned a risk score
      proportional to its regression coefficient value. Health risk scores were
      calculated for each patient and the HR of all-cause premature mortality was
      calculated according to risk score. RESULTS: Current smoking and drinking, high
      body mass index, less sleep hours, and less education were significantly
      associated with all-cause premature mortality, while regular exercise was
      associated with a reduced risk. When combined by health risk score, there was a
      strong trend for increased mortality risk with increased score (p-trend < 0.01).
      When compared with the 1-9 score group, HRs of the 10-19 and 20-28 score groups
      were 2.58 (95% confidence intervals [CIs], 2.19 to 3.03) and 7.09 (95% CIs, 5.21
      to 9.66), respectively. CONCLUSIONS: Modifiable risk factors, such as smoking,
      drinking, and regular exercise, have considerable impact on premature mortality
      and should be assessed in combination.

PMID- 22389755
TI  - Indoor physical activity reduces all-cause and cardiovascular disease mortality
      among elderly women.
AB  - OBJECTIVES: The aim of this study was to investigate whether a medium to high
      degree of total physical activity and indoor physical activity were associated
      with reduced all-cause and cardiovascular mortality among elderly Korean women.
      METHODS: A prospective cohort study was done to evaluate the association between
      physical activity and mortality. The cohort was made up of elderly (>= 65 years
      of age) subjects. Baseline information was collected with a self-administered
      questionnaire and linked to death certificates retrieved from a database. Cox
      proportional hazard models were used to estimate the hazard ratios (HRs) with 95%
      confidence interval (CI) levels. RESULTS: Women who did not suffer from stroke,
      cancer, or ischemic heart disease were followed for a median of 8 years (n=5079).
      A total of 1798 all-cause deaths were recorded, of which 607 (33.8%) were due to
      cardiovascular disease. The group with the highest level of total physical
      activity and indoor physical activity was significantly associated to a reduced
      all-cause mortality (HR, 0.60; 95% CI, 0.51 to 0.71 and HR, 0.58; 95% CI, 0.50 to
      0.67, respectively) compared to the group with the lowest level of total physical
      activity and indoor physical activity. Additionally, the group with the highest
      level of total physical activity and indoor physical activity was significantly
      associated to a lower cardiovascular disease mortality (HR, 0.53; 95% CI, 0.40 to
      0.71 and HR, 0.51; 95% CI, 0.39 to 0.67, respectively) compared to the group with
      the lowest level of total physical activity and indoor physical activity.
      CONCLUSIONS: Our study showed that regular indoor physical activity among elderly
      Korean women has healthy benefits.

PMID- 22389757
TI  - The nonlinear association between Internet using time for non-educational
      purposes and adolescent health.
AB  - OBJECTIVES: This study was performed to consider the association between Internet
      using time for non-educational purposes and adolescent health, and to examine how
      health status differs between Internet users and non-users. METHODS: We analyzed
      2009 data from the Korea Adolescent Risk Behavior Web-Based Survey, conducted on
      a nationally representative sample of students in grades 7 to 12. A total of 75
      066 adolescents were categorized into four groups according to their Internet
      using time excluding using for educational purposes: non-Internet users (NIUs),
      occasional Internet users (OIUs) (<1 h/d), moderate Internet users (MIUs) (>= 1
      and <2 h/d), and heavy Internet users (HIUs) (>= 2 h/d). Health factors included
      eight health risk behavior indices, four mental health indices and six physical
      health indices. RESULTS: THE DISTRIBUTION OF INTERNET USE WAS AS FOLLOWS: NIUs
      17.4%, OIUs 68.1%, MIUs 12.7%, and HIUs 1.7%. In multivariate analysis, using
      OIUs as a reference, U- or J-shaped associations were observed for five health
      risk behavior indices (current smoking, current drinking, drug abuse, sexual
      intercourse, sedentary behavior on weekdays) and four mental health indices
      (stressed, depressed, suicidal ideation, attempted suicide) in both genders.
      After removing confounding effects, including age, region, school type,
      subjective school record, subjective economic status, presence of parents, living
      with family, and sedentary behavior, these associations were still observed.
      CONCLUSIONS: Health professionals should consider both Internet non-users (for
      non-educational purposes) and heavy users to be high-risk groups in terms of
      health status. Also, more well-designed studies are needed to clarify what
      factors are working in these nonlinear associations.

PMID- 22389756
TI  - Social determinants of smoking behavior: the Healthy Twin Study, Korea.
AB  - OBJECTIVES: The purpose of this study was to identify any influence of
      socioeconomic status on smoking and smoking cessation in a situation where
      genetic factors are controlled. METHODS: The sample for this study was 2502
      members of the twins and families cohort who participated in the Korean Healthy
      Twins Study from 2005 to 2009. Groups of brothers or sisters, including twins and
      fraternal twins, were compared in terms of smoking and smoking cessation
      behaviors according to differences in socioeconomic status and gender. RESULTS:
      In a situation with complete control of genetic factors, results showed that the
      daily smoking amount, cumulative smoking amount, and dependence on nicotine
      decreased with higher-status occupations, and the rate of smoking and amount of
      cumulative smoking decreased with higher levels of education. Regarding smoking
      cessation behavior, a higher level of education was associated with a lower
      smoking cessation rate, and no significant gender differences were found.
      CONCLUSIONS: Environmental factors had a stronger influence on smoking behavior
      than did genetic factors. Genetic factors had greater influence on smoking
      cessation than did environmental factors; however, this requires verification in
      further studies.

PMID- 22389758
TI  - Changes in dietary behavior among adolescents and their association with
      government nutrition policies in Korea, 2005-2009.
AB  - OBJECTIVES: This study was conducted to observe recent changes in adolescents'
      dietary behavior and indirectly evaluate the effects of the government's
      nutritional policies in Korea. METHODS: We analyzed the secular trends in seven
      dietary behaviors using the Korea Youth Risk Behavior Web-based Survey data from
      2005 to 2009. Through literature review, we included the policies implemented for
      the improvement of adolescents'dietary behaviors during the same periods.
      RESULTS: The significant linear trends were observed in all dietary behaviors
      (p<0.05). Overall, all behaviors except the fruit intake rate were desirably
      changed during five years but undesirable changes were observed between 2008 and
      2009 in all behaviors. Within those periods, several policies were implemented
      including 'Ban on carbonated-beverages in school', 'Green Food Zone', etc.
      Despite confirmed evidence of their effects, the policies on individual behavior
      such as nutrition education didn't influence the prevalence of dietary behaviors
      because they were conducted to too limited persons. Policies on the school
      environmental improvement, such as ban on carbonated beverage in school, were
      more effective because they decreased the exposure of undesirable food
      environment. However, for effect of Green Food Zone improving community
      environment we couldn't come to a conclusion because of too short period after
      full implementation. CONCLUSIONS: Among government nutrition policies conducted
      from 2005 to 2009, those on environmental improvement, especially in school, were
      more effective than those on individual behavior. Therefore, the development and
      implement of policies on school environmental improvement are needed in Korea.

PMID- 22389759
TI  - Understanding the roles of gingival beta-defensins.
AB  - Gingival epithelium produces beta-defensins, small cationic peptides, as part of
      its contribution to the innate host defense against the bacterial challenge that
      is constantly present in the oral cavity. Besides their functions in healthy
      gingival tissues, beta-defensins are involved in the initiation and progression,
      as well as restriction of periodontal tissue destruction, by acting as
      antimicrobial, chemotactic, and anti-inflammatory agents. In this article, we
      review the common knowledge about beta-defensins, coming from in vivo and in
      vitro monolayer studies, and present new aspects, based on the experience on
      three-dimensional organotypic culture models, to the important role of gingival
      beta-defensins in homeostasis of the periodontium.

PMID- 22389760
TI  - Design of clinical trials for biomarker research in oncology.
AB  - The developmental pathway from discovery to clinical practice for biomarkers and
      biomarker-directed therapies is complex. While several issues need careful
      consideration, two critical issues that surround the validation of biomarkers are
      the choice of clinical trial design (which is based on the strength of the
      preliminary evidence and marker prevalence) and the biomarker assay related
      issues surrounding the marker assessment methods such as the reliability and
      reproducibility of the assay. This review focuses on trial designs for marker
      validation, both in the setting of early phase trials for initial validation, as
      well as in the context of larger definitive trials. Designs for biomarker
      validation are broadly classified as retrospective (i.e., using data from
      previously well-conducted, randomized, controlled trials) or prospective
      (enrichment, allcomers or adaptive). We believe that the systematic evaluation
      and implementation of these design strategies are essential to accelerate the
      clinical validation of biomarker-guided therapy, thereby taking us a step closer
      to the goal of personalized medicine.

PMID- 22389761
TI  - Communication during sex among female bonobos: effects of dominance, solicitation
      and audience.
AB  - Bonobo females frequently form close bonds, which give them social power over
      other group members. One potential mechanism to facilitate female bonding is the
      performance of sexual interactions. Using naturalistic observations and
      experiments, we found various patterns that determined female-female sexual
      interactions. First, while low-ranked females interacted with all females, sexual
      interactions between high-ranked females were rare. Second, during genital
      contacts, females sometimes produced 'copulation calls', which were significantly
      affected by the rank of the caller and partner, as well as the solicitation
      direction. Third, there was a significant effect of the alpha female as a
      bystander, while variables relating to physical experience had no effects.
      Overall, results highlight the importance of sexual interactions for bonobo
      female social relations. Copulation calls are an important tool during this
      process, suggesting that they have become ritualised, beyond their reproductive
      function, to serve as broader social signals in flexible and potentially
      strategic ways.

PMID- 22389762
TI  - Quantum phase slip phenomenon in ultra-narrow superconducting nanorings.
AB  - The smaller the system, typically - the higher is the impact of fluctuations. In
      narrow superconducting wires sufficiently close to the critical temperature T(c)
      thermal fluctuations are responsible for the experimentally observable finite
      resistance. Quite recently it became possible to fabricate sub-10 nm
      superconducting structures, where the finite resistivity was reported within the
      whole range of experimentally obtainable temperatures. The observation has been
      associated with quantum fluctuations capable to quench zero resistivity in
      superconducting nanowires even at temperatures T->0. Here we demonstrate that in
      tiny superconducting nanorings the same phenomenon is responsible for suppression
      of another basic attribute of superconductivity - persistent currents -
      dramatically affecting their magnitude, the period and the shape of the current
      phase relation. The effect is of fundamental importance demonstrating the impact
      of quantum fluctuations on the ground state of a macroscopically coherent system,
      and should be taken into consideration in various nanoelectronic applications.

PMID- 22389763
TI  - Win-stay, lose-switch and public information strategies for patch fidelity of
      songbirds with rare extra-pair paternity.
AB  - Determining where organisms breed and understanding why they breed in particular
      locations are fundamental biological questions with conservation implications.
      Breeding-site fidelity is common in migratory, territorial songbirds and is
      typically thought to occur following reproductive success with a social mate and
      success of nearby conspecifics. It is currently unknown if frequency of extra
      pair paternity in a population influences use of information about reproductive
      success of nearby conspecifics for site fidelity decisions. We investigated patch
      fidelity of white-eyed vireos (Vireo griseus) based on reproductive success and
      quantified frequency of extra-pair paternity. We found support only for females
      making patch fidelity decisions following reproductive success with a social
      mate. Patch fidelity of males was not associated with reproductive success of
      nearby conspecifics, suggesting males may not use this information when extra
      pair paternity is infrequent or the association is non-existent in this species.

PMID- 22389764
TI  - TNF-alpha and TGF-beta counter-regulate PD-L1 expression on monocytes in systemic
      lupus erythematosus.
AB  - Monocytes in patients with systemic lupus erythematosus (SLE) are
      hyperstimulatory for T lymphocytes. We previously found that the normal program
      for expression of a negative costimulatory molecule programmed death ligand-1 (PD
      L1) is defective in SLE patients with active disease. Here, we investigated the
      mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1
      expression on cultured SLE monocytes correlated with TNF-alpha expression.
      Exogenous TNF-alpha restored PD-L1 expression on lupus monocytes. Conversely, TGF
      beta inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on
      healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by
      opposing actions of TNF-alpha and TGF-beta. As PD-L1 functions to fine tune
      lymphocyte activation, dysregulation of cytokines resulting in reduced expression
      could lead to loss of peripheral T cell tolerance.

PMID- 22389765
TI  - Elementary processes governing the evolution of road networks.
AB  - Urbanisation is a fundamental phenomenon whose quantitative characterisation is
      still inadequate. We report here the empirical analysis of a unique data set
      regarding almost 200 years of evolution of the road network in a large area
      located north of Milan (Italy). We find that urbanisation is characterised by the
      homogenisation of cell shapes, and by the stability throughout time of high
      centrality roads which constitute the backbone of the urban structure, confirming
      the importance of historical paths. We show quantitatively that the growth of the
      network is governed by two elementary processes: (i) 'densification',
      corresponding to an increase in the local density of roads around existing urban
      centres and (ii) 'exploration', whereby new roads trigger the spatial evolution
      of the urbanisation front. The empirical identification of such simple elementary
      mechanisms suggests the existence of general, simple properties of urbanisation
      and opens new directions for its modelling and quantitative description.

PMID- 22389766
TI  - Identification of hot and cold spots in genome of Mycobacterium tuberculosis
      using Shewhart Control Charts.
AB  - The organization of genomic sequences is dynamic and undergoes change during the
      process of evolution. Many of the variations arise spontaneously and the observed
      genomic changes can either be distributed uniformly throughout the genome or be
      preferentially localized to some regions (hot spots) compared to others.
      Conversely cold spots may tend to accumulate very few variations or none at all.
      In order to identify such regions statistically, we have developed a method based
      on Shewhart Control Chart. The method was used for identification of hot and cold
      spots of single-nucleotide variations (SNVs) in Mycobacterium tuberculosis
      genomes. The predictions have been validated by sequencing some of these regions
      derived from clinical isolates. This method can be used for analysis of other
      genome sequences particularly infectious microbes.

PMID- 22389768
TI  - Combined use of a solid-phase hexapeptide ligand library with liquid
      chromatography and two-dimensional difference gel electrophoresis for intact
      plasma proteomics.
AB  - The intact plasma proteome is of great interest in biomarker studies because
      intact proteins reflect posttranslational protein processing such as
      phosphorylation that may correspond to disease status. We examined the utility of
      a solid-phase hexapeptide ligand library in combination with conventional plasma
      proteomics modalities for comprehensive profiling of intact plasma proteins.
      Plasma proteins were sequentially fractionated using depletion columns for
      albumin and immunoglobulin, and separated using an anion-exchange column.
      Proteins in each fraction were treated with a solid-phase hexapeptide ligand
      library and compared to those without treatment. Two-dimensional difference gel
      electrophoresis demonstrated an increased number of protein spots in the treated
      samples. Mass spectrometric studies of these protein spots with unique intensity
      in the treated samples resulted in the identification of high- and medium
      abundance proteins. Our results demonstrated the possible utility of a solid
      phase hexapeptide ligand library to reveal greater number of intact plasma
      proteins. The characteristics of proteins with unique affinity to the library
      remain to be clarified by more extensive mass spectrometric protein
      identification, and optimized protocols should be established for large-scale
      plasma biomarker studies.

PMID- 22389767
TI  - Assessment of extracts from red yeast rice for herb-drug interaction by in-vitro
      and in-vivo assays.
AB  - Red yeast rice (RYR) is made by fermenting the yeast Monascus purpureus over
      rice. It is a source of natural red food colorants, a food garnish and a
      traditional medication. Results of the current study demonstrated that polar
      fractions of the RYR preparations contained herbal-drug interaction activity,
      which if left unremoved, enhanced P-glycoprotein activity and inhibited the major
      drug metabolizing cytochromes P450, i,e, CYP 1A2, 2C9 and 3A4. The data from Caco
      2 cell absorption and animal model studies further demonstrated that the
      pharmacokinetic modulation effect by RYR preparations containing the polar
      fractions ("untreated" preparation) was greater than that from RYR preparations
      with the polar fractions removed ("treated" preparation). The data indicates a
      potential for herb-drug interactions to be present in RYR commonly sold as
      nutritional supplements when the polar fractions are not removed and this should
      be taken into consideration when RYR is consumed with medications, including
      verapamil.

PMID- 22389769
TI  - Effect of alcohol structure on the optimum condition for novozym 435-catalyzed
      synthesis of adipate esters.
AB  - Immobilized Candida antarctica lipase B, Novozym 435, was used as the biocatalyst
      in the esterification of adipic acid with four different isomers of butanol (n
      butanol, sec-butanol, iso-butanol, and tert-butanol). Optimum conditions for the
      synthesis of adipate esters were obtained using response surface methodology
      approach with a four-factor-five-level central composite design concerning
      important reaction parameters which include time, temperature, substrate molar
      ratio, and amount of enzyme. Reactions under optimized conditions has yielded a
      high percentage of esterification (>96%) for n-butanol, iso-butanol, and sec
      butanol, indicating that extent of esterification is independent of the alcohol
      structure for primary and secondary alcohols at the optimum conditions. Minimum
      reaction time (135 min) for achieving maximum ester yield was obtained for iso
      butanol. The required time for attaining maximum yield and also the initial rates
      in the synthesis of di-n-butyl and di-sec-butyl adipate were nearly the same.
      Immobilized Candida antarctica lipase B was also capable of esterifying tert
      butanol with a maximum yield of 39.1%. The enzyme is highly efficient biocatalyst
      for the synthesis of adipate esters by offering a simple production process and a
      high esterification yield.

PMID- 22389770
TI  - The comparative study of the effectiveness of cimetidine, ranitidine, famotidine,
      and omeprazole in treatment of children with dyspepsia.
AB  - Background. Functional dyspepsia is a common chronic disorder with non specific
      upper abdominal pain or discomfort. Different approaches with anti-secretory,
      spasmolytic, prokinetic and anti-inflammatory effects and most preferably
      reduction of visceral hypersensitivity seem logical. In this study, we compared
      the effectiveness of the four most drugs used for treatment of dyspepsia in
      children. Methods. 169 patients between 2 to 16 years old that 47.3% was male and
      52.7% was female were enrolled in this clinical trial study by the diagnosis of
      functional dyspepsia. Then for each patient one of the drugs; Omeprazole,
      Famotidine, Ranitidine or Cimetidine was administered, for a period of 4 weeks.
      Patients were followed after 2 and 6 weeks from the beginning of the treatment.
      Results. The distribution of drugs between these patients were including; 21.9%
      with Cimetidine, 21.3% with Famotidine, 30.8% with Omeperazole and 26% with
      Ranitidine that the proportion of patients with all symptoms relief were: 21.6%
      for Cimetidine, 44.4% for Famotidine, 53.8% for Omeprazole and 43.2% for
      Cimetidine (P = .024). In followups within 2 and 6 weeks after beginning medical
      therapy, no side effects due to drugs were seen. Conclusion. If a cure is defined
      as all symptoms relief after a period of 4 weeks treatment, our findings showed
      that Omeperazole are superior to Ranitidine, Famotidine, and Cimetidine for
      management of functional dyspepsia.

PMID- 22389771
TI  - How pediatricians can deal with children who have been sexually abused by family
      members.
AB  - The present paper discusses children who have been the victims of sexual abuse in
      their own family. It focuses on the special role of pediatricians and medical
      staff in identifying such children and providing them with initial assistance by
      reporting the situation to the authorities. The first part of the paper surveys
      the short- and long-term effects of childhood sexual abuse, including the
      physical and emotional impact of sexual exploitation and severe neglect. This
      section discusses the symptoms shown by abused children, and how they express and
      deal with their trauma. It is extremely important for pediatricians to be
      sensitive to the possibility of patients being abused at home, as this is an area
      still largely regarded as a societal taboo. Also included in this section a
      discussion of the effects that are manifested when the victim has grown to
      adulthood, such as personality disorders. The second part of the paper deals with
      how pediatricians must act when they encounter such a situation in which they
      suspect sexual abuse in the family. They should strive to identify the problem
      and bring it to the attention of the authorities. Discovery of the problem is the
      most vital part of the path to the victim's recovery. The paper also discusses
      the aspect of treatment, advising doctors who encounter this problem on ways of
      dealing with it.

PMID- 22389772
TI  - A pilot study of social competence assessment using interaction rating scale
      advanced.
AB  - Purpose. The purpose of this paper is to clarify the validity of the Interaction
      Rating Scale Advanced (IRSA) as an evidence-based practical index of social
      skills. Methods. The participants in our study were 17 high school students. The
      participants completed the five-minute interaction session and were observed
      using the IRSA. Their teacher evaluated their social competence based on regular
      observation in school. Results. The results indicated the high correlation
      between IRSA scores and teacher's practical evaluation. IRSA can measure social
      competence with high validity. Conclusion. The IRSA provides further evidence of
      the fact that in order to study social competence development, it is important to
      evaluate various features of the interaction like IRSA subscales.

PMID- 22389773
TI  - Disparities in the Clinical Encounter: Virginia's African American Children with
      Special Health Care Needs.
AB  - This study analyzed Virginia data from the most recent National Survey of
      Children with Special Health Care Needs. Logistic regression models were run for
      six Maternal and Child Health Bureau core outcomes and included demographics,
      child characteristics, health care providers, and health care access variables as
      predictors. Race/ethnicity disparities were judged to be present if the
      race/ethnicity variable was a significant predictor in the final model. Examining
      the components of disparate outcomes, African American children were found to be
      less likely than their white counterparts to have a usual source for sick and
      preventive care and to have a personal doctor or nurse. Their parents were less
      likely to say that doctors spent enough time, listened carefully, were sensitive
      to values and customs, and made them feel like a partner. These findings
      emphasize the need to examine health care disparities at a state level in order
      to guide efforts at remediation.

PMID- 22389774
TI  - An exploratory investigation of some statistical summaries of oximeter oxygen
      saturation data from preterm babies.
AB  - Aim. To explore the potential usefulness of the mean, standard deviation (SD),
      and coefficient of variation (CV = SD/mean) of oximeter oxygen saturations in the
      clinical care of preterm babies. Methods. This was an exploratory investigation
      involving 31 preterm babies at 36 weeks postmenstrual age. All babies were
      healthy, but two were considered to be clinically unstable and required greater
      attention. Each baby's oxygen saturations were recorded using an oximeter and
      summarized by the mean, SD, and CV. The potential usefulness of each measure was
      assessed by its ability to distinguish the two unstable babies from the others.
      This was achieved using box plots and hierarchical clustering together with the
      Calinski-Harabasz (CH) index to quantify clustering performance (higher CH index
      indicates stronger clustering outcome). Results. The box plots flagged both
      unstable babies as outliers and none of the other babies. Successful clustering
      of the stable and unstable babies was achieved using the CV (CH = 72.8) and SD
      (CH = 63.3) but not with the mean. Conclusion. Taking the box plots and
      clustering results together, it seems plausible that variability might be more
      effective than mean level for detecting instability in oxygen saturation in
      preterm babies and that the combination of variability and level through the CV
      might be even better.

PMID- 22389775
TI  - Impact of Inflammatory Bowel Disease upon Growth in Children and Adolescents.
AB  - The inflammatory bowel diseases (IBDs) are chronic inflammatory processes
      affecting the gastrointestinal tract. When diagnosed in childhood and
      adolescence, IBD almost always impacts adversely upon the nutritional state of
      the patient. Weight loss and impaired linear growth may be present at diagnosis
      or subsequently. Further potential nutritional consequences in childhood IBD
      include malnutrition, anaemia, osteopaenia, and delayed puberty. Understanding
      the nutritional aspects of IBD is paramount in growing children, especially those
      entering and advancing through puberty. This paper focuses upon the nutritional
      impacts of IBD in children and adolescents.

PMID- 22389776
TI  - The use of dexamethasone in bacterial meningitis in children and adults: a
      retrospective analysis.
AB  - Bacterial meningitis is a life-threatening illness that results from bacterial
      infection of the meninges and is associated with high mortality and morbidity
      rate, especially when the Streptococcus pneumoniae is the causative agent.
      Dexamethasone as adjunctive therapy to antibiotics does not influence the outcome
      or the complications in children as well as in adults suffering bacterial
      meningitis. However, we identified some prognostic parameters in the outcome of
      bacterial meningitis, and when dexamethasone was given in presence of at least
      one of 3 poor prognostic CSF parameters (WBC < 1000/mm(3), glucose < 20 mg/dl,
      lactate > 10 mg/dl) it substantially improved the outcome.

PMID- 22389777
TI  - Salt losing obstructive uropathy with paradoxically low urinary sodium
      concentration: salt entrapment in an obstructed ectopic ureterocele.
AB  - A 6-month-old hyponatremic female with failure to thrive had low urinary sodium
      concentration. Renal sonography revealed a duplex left collecting system with
      obstruction of the upper moiety as a blind-ended ectopic ureterocele extending to
      the bladder base. The echogenicity of the urine within the upper pole system was
      greater than the bladder contents. We believed that low urinary sodium
      concentration represented a false negative test and the salt loss by the
      obstructed left kidney was entrapped in the upper pole collecting system. Prior
      to ureterocele repair, intraoperative bladder and ureterocele aspirates revealed
      discordant sodium concentration supporting the sonographic conclusion.

PMID- 22389778
TI  - Knowledge and Practice Gaps among Pediatric Nurses at a Tertiary Care Hospital
      Karachi Pakistan.
AB  - The advancement in medical science has created health care environments that
      require nursing professionals who posses specialized clinical knowledge and
      skills to provide care and deal with critically and acutely ill children. This
      study explored gaps between knowledge and practice as perceived by the registered
      nurses of pediatric units by further recommending the changes suggested by them.
      A descriptive exploratory study design under the quantitative research
      methodology was utilized using universal sampling of all pediatric nurses working
      at a tertiary care hospital in Karachi, Pakistan. The gaps between knowledge and
      practice, as perceived by the participants, were categorized into five major
      categories: (1) medication (34%), (2) skills (28.3%), (3) knowledge (13.36%), (4)
      handling of code blue and intubations (12.6%), and (5) operating medical devices
      (11.58%). As a result, anxiety and incompetency were notably seen in the
      participants which had great amount of impact on the level of care provided to
      the patients. The implications of the findings for quality patient care were also
      analyzed.

PMID- 22389779
TI  - Glomerulonephritis with crescents in children: etiology and predictors of renal
      outcome.
AB  - Objective. To investigate the clinicopathological features and outcome of
      glomerulonephritis with crescents among Saudi children. Method. This is a
      retrospective study of cases of crescentic glomerulonephritis (CrGN) seen over a
      9-year period. Histological features and renal function were recorded. Results.
      Thirty-seven cases were enrolled. The mean percent of glomeruli with crescents
      was 39% (+/-19). Lupus nephritis (LN) was the commonest etiology (54.1%). At
      presentation, the serum creatinine (SCr) was 218.2 (+/-174.3) umol/l, and 57.1%
      of the cases had nephrotic range proteinuria. By the end of the observation
      period, SCr dropped to 81.0 (+/-67.7) umol/l (P = 0.001). Worsening renal
      function was associated with younger age (P = 0.002), non-LN etiology (P = 0.01),
      more crescents (P = 0.019), and ATN (P = 0.05). At the end of the followup, more
      patients in the LN group were dialysis-free (P = 0.017) and had improved renal
      function (0.01) than in the non-LN group. Using multivariate analysis, the only
      independent factor found to predict need for dialysis or change in SCr level was
      percent of globally sclerosed glomeruli (P = 0.034). Conclusion. LN is the main
      cause of CrGN in our cohort of children. The LN group had less globally
      sclerorsed glomeruli and better renal prognosis than the non-LN group.

PMID- 22389780
TI  - To explore the experiences of women on reasons in initiating and maintaining
      breastfeeding in urban area of karachi, pakistan: an exploratory study.
AB  - This is an exploratory study that explores the experiences of lactating women in
      initiating, continuing, or discontinuing breastfeeding in an urban area of
      Karachi, Pakistan. Objectives. To explore the experiences of lactating women and
      to understand their support and hindering mechanisms in initiating and
      maintaining breastfeeding. Methods. This is an exploratory design assisting in
      exploring the participant's experiences of initiating and maintaining
      breastfeeding to better understand their world. Purposive sampling was used, and
      data was analyzed through manual thematic analysis. Results. The data revealed
      that mother's knowledge, sociocultural environment, breastfeeding decision, and
      self- and professional support acted as driving forces for the participants.
      However, sociocultural environment, physiological changes, time management, and
      being a housewife to breastfeed their children were all challenges and barriers
      that the participants thought hindered their breastfeeding initiation and
      maintenance. Conclusion. Breastfeeding is a natural but taxing phenomenon, and
      breastfeeding mothers experience supporting and hindering factors in initiating
      and maintaining breastfeeding.

PMID- 22389781
TI  - Postoperative dissecting ventricular septal hematoma: recognition and treatment.
AB  - Dissecting ventricular septal hematoma (DVSH) rarely occurs after repair of a
      ventricular septal defect (VSD) but can lead to serious complications such as
      septal rupture, myocardial rupture, cardiogenic shock, heart block, outflow
      obstruction, cardiac tamponade, abscess transformation, and death. This paper
      describes the diagnosis and management of acute, severe, left ventricular outflow
      tract obstruction caused by the development of a DVSH after VSD repair.

PMID- 22389782
TI  - Hemolytic-Uremic Syndrome in Uberlandia, MG, Brazil.
AB  - Purpose. To analyze the epidemiological, clinical, and laboratory characteristics
      of hemolytic-uremic syndrome (HUS) in Uberlandia, MG, Brazil. Methods. A
      historical cohort study was performed encompassing a ten-year period from January
      1994 to January 2004 in the Department of Pediatric Nephrology at a full-service
      hospital; demographic factors, triggering factors, time of hospitalization,
      supportive therapy, and disease progression were analyzed. Results. Twenty-seven
      children aged 5 to 99 months (median age of 14 months) were studied; 70.4% were
      male. Of the 27 patients, 77.8% were from urban areas and 18.5% were from rural
      areas. Eight of the patients (29.6%) were reported to drink raw milk, and
      clinical diarrhea was reported in 81.5% of cases. The most common signs and
      symptoms were fever and vomiting (85.1%), anuria (63.0%), seizure (33.0%),
      cardiac involvement (11.0%), and acute pulmonary edema (7.4%). Dialysis was
      performed on 20 patients (74%). The mean hospital stay was 24 days (range: 13 to
      36 days). While monitoring the patients, 2 died (7.4%), 3 developed chronic
      kidney disease (11.0%), and 21 (77.8%) developed hypertension. Conclusion. Our
      results emphasize the possibility of diagnosing HUS as a cause of renal failure
      in childhood in both typical (postdiarrheal) and atypical forms and suggest that
      an investigation of the etiological agent should be made whenever possible.

PMID- 22389783
TI  - GCK-MODY (MODY 2) Caused by a Novel p.Phe330Ser Mutation.
AB  - Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes
      inherited as an autosomal dominant trait. The second most common cause is GCK
      MODY due to heterozygous mutations in the GCK gene which impair the glucokinase
      function through different mechanisms such as enzymatic activity, protein
      stability, and increased interaction with its receptor. The enzyme normally acts
      as a glucose sensor in the pancreatic beta cell and regulates insulin secretion.
      We report here a three-generation nonobese family diagnosed with diabetes. All
      affected family members presented with mild hyperglycemia and mostly slightly
      elevated hemoglobin A1c values. Genetic testing revealed a novel heterozygous T 
      > C exchange in exon 8 of the GCK gene which resulted in a phenylalanine(330) TTC
      -> serine (TCC)/p.Phe330Ser/F330S substitution.

PMID- 22389784
TI  - Needle in a haystack-parathyroid gland in a 10-day old infant: a case report and
      literature review.
AB  - Neonatal severe primary hyperparathyroidism (NSPHT) is a rare autosomal recessive
      disorder of calcium homeostasis. It presents shortly after birth and is
      characterized by striking hyperparathyroidism, marked hypercalcemia, and
      hyperparathyroid bone disease. It is caused by mutations of the calcium-sensing
      receptor (CASR), the ionized calcium sensor for the parathyroid cells, the
      parafollicular thyroid C cells, and the kidney epithelium, as well as cells in
      bone and intestine. Without early intervention, which frequently requires
      surgical removal of the hyperplastic parathyroids, the patients often succumb to
      complications of hypercalcemia and respiratory failure. Finding the parathyroid
      gland in small neonates is not an easy task. Here we report on a patient with
      neonatal hyperparathyroidism who was treated by total parathyroidectomy and
      discuss the various ways of helping to find the parathyroid glands during surgery
      at this young age.

PMID- 22389785
TI  - Prevalence of ADHD Symptoms amonge Male Preschoolers Based on Different
      Informants in Ahvas City of Iran.
AB  - Background. This cross-sectional study evaluated rate of reported ADHD symptoms
      among male preschoolers in Ahvaz by different informants and rate of their
      agreement. Method. One hundred ninety-two 5-6-year old boys from nine
      kindergartens in Ahvaz were selected. Teacher and parents' Conners ADHD rating
      scales were used. Findings. For 133 children, questionnaires were returned.
      Prevalence of children with positive questionnaire was 24.06%, with only parent
      questionnaire was 4.51%, with only teacher questionnaire was 17.29%, and with
      both informants was 2.25%. Teacher-parent agreement was low (P = 0.0001).
      Conclusions. ADHD symptoms are frequently reported by informants and may be more
      reported by teachers than parents and teacher-parent agreement may be low.
      Interview with different informants and observation of child behavior are needed
      for documentation of diagnosis.

PMID- 22389786
TI  - A case of pemphigus herpetiformis in a 12-year-old male.
AB  - Pemphigus herpetiformis (PH) is one of the less common forms of pemphigus. PH in
      children is unreported. We describe a case of a child who developed PH.
      Observation. A 12-year-old boy was seen at our department with erosive plaques,
      vesicles, and crusted cutaneous lesions associated with severe itching persisting
      for six months. Histologic examination showed an intraepidermal bulla containing
      rare acantholytic epidermal cells with eosinophilic spongiosis. Direct
      immunofluorescence demonstrated intercellular Ig G and C3 deposit. The serum
      titer of antibodies against intercellular epidermal was 1/200 UI/l. Diagnosis of
      PH was made, and treatment with Dapsone 2 mg/kg per day resulted in total
      clinical remission. However, two months later, new vesicles reappeared and
      treatment was begun with prednisone at a dose of 2 mg/kg daily. There was a very
      good response. Discussion. Childhood pemphigus herpetiformis is a rare disease,
      often initially misdiagnosed. It must not be forgotten that the disease is a
      possible cause of erosive mucocutaneous disease in children.

PMID- 22389787
TI  - Childhood asthma utilization rates in a nonsmoking population of utah compared to
      state and national rates.
AB  - Risk factors, such as parental smoking, are commonly associated with increased
      asthma symptoms and hospitalizations of children. Deseret Mutual Benefits
      Administrators (DMBA) is the health insurer for employees of The Church of Jesus
      Christ of Latter-day Saints and their families. Due to religious proscription,
      employees abstain from alcohol and tobacco use, creating a cohort of children not
      exposed to parental smoking. Calculation of hospitalization rates for DMBA, Utah,
      and the US were made in children to compare rates between a nonsmoking population
      and general populations. Compared to DMBA, rate ratios for asthma hospitalization
      and emergency department asthma visits were higher for the US and Utah. The
      incidence of hospital outpatient department and physician office visits was
      significantly greater for the US population compared to the DMBA. This study
      demonstrates a decreased need for health services used by children not exposed to
      second-hand smoke.

PMID- 22389788
TI  - Multimodal behavior program for ADHD incorporating yoga and implemented by high
      school volunteers: a pilot study.
AB  - A low-cost resource approach to ADHD therapy would be a practical approach to
      treating children in developing countries. Research has shown that ADHD is
      prevalent in all areas of the world, and yet treatment for children in more
      impoverished countries is still lacking. The approach taken was to combine yoga
      and meditation combined with multimodal behavioral therapy program for children
      ageing 6 to 11. The program was kept low cost by using trained high school
      volunteers and integrating the program within the public school. After 6 weeks of
      the program, 90.5% of children showed improvement as measured by their
      performance impairment score, a measurement of academic performance. Parent and
      Teacher evaluations of behavior also found improvement as 25 of the 64 children
      (39.1%) improved into the normal range as measured by the Vanderbilt
      questionnaire. Moreover, children could successfully learn both yoga and
      meditation from high school students irrespective of their age, ADHD type, or
      initial performance impairment. The results demonstrate efficacy of a multimodal
      behavioral program incorporating yoga and meditation. The use of high school
      volunteers from schools in the area demonstrates an effective low-cost and
      universally applicable approach.

PMID- 22389789
TI  - 22q13.32 deletion and duplication and inversion in the same family: a rare
      occurrence.
AB  - Chromosome 22q13.3 deletion syndrome is a well-recognized cause of global
      developmental delay, while duplication of the same chromosome is a rare
      occurrence. The presence of both abnormalities in the same family has never been
      reported, to our knowledge. We report a rare occurrence of 22q13.3 duplication
      and 22q13.3 deletion in siblings, as a consequence of a mother's inversion on her
      22nd chromosome (p13;q13.32). A 6 year old male was noted in infancy to have mild
      global developmental delay without dysmorphic features. His genetic testing
      revealed he had 22q13.3 duplication to the terminus. His 4 year old brother was
      noted in early infancy to have severe global developmental delay and dysmorphic
      features related to 22q13.3 deletion to the terminus. Their mother had a long
      inversion on her 22nd chromosome. Genetic tests for their father and eldest
      brother were unremarkable. The mother's inversion may rearrange to form 22q
      duplication or deletion when passed on to children. The chance of a child born
      with a chromosome imbalance is as high as 50%.

PMID- 22389791
TI  - Professional Caregiver's View on Mental Health in Parents of Children with
      Developmental Disabilities: A Nationwide Study of Institutions and Consultation
      Centers in Japan.
AB  - Parents of children with intellectual disabilities and/or physical disabilities
      are supposed to have an increased risk for parenting stress and psychological
      distress. We as professional caregivers sometimes experience difficulties in
      keeping good relations or communicating with the parents. Professional workers in
      460 institutions and consultation centers throughout Japan answered a
      questionnaire on their clinical experiences. About 90% of the facilities
      experienced "distressed parents," and the parents' condition such as mental
      health seemed to influence this. Signs of a depressive state were the most common
      psychiatric disturbances detected, and it was notable in the pervasive
      developmental disorder group. More welfare support, presence of support groups,
      support from other family members, and medical treatment of the parents' problems
      were considered to be helpful and thus requested to be improved. Training more
      professionals who can properly deal with the parents' mental health needs is an
      urgent matter that must be tackled.

PMID- 22389792
TI  - Management of acute spinal fractures in ankylosing spondylitis.
AB  - Ankylosing Spondylitis (AS) is a multifactorial and polygenic rheumatic condition
      without a well-understood pathophysiology (Braun and Sieper (2007)). It results
      in chronic pain, deformity, and fracture of the axial skeleton. AS alters the
      biomechanical properties of the spine through a chronic inflammatory process,
      yielding a brittle, minimally compliant spinal column. Consequently, this patient
      population is highly susceptible to unstable spine fractures and associated
      neurologic devastation even with minimal trauma. Delay in diagnosis is not
      uncommon, resulting in inappropriate immobilization and treatment. Clinicians
      must maintain a high index of suspicion for fracture when evaluating this group
      to avoid morbidity and mortality. Advanced imaging studies in the form of
      multidetector CT and/or MRI should be employed to confirm the diagnosis. Initial
      immobilization in the patient's preinjury alignment is mandatory to prevent
      iatrogenic neurologic injury. Both nonoperative and operative treatments can be
      employed depending on the patient's age, comorbidities, and fracture stability.
      Operative techniques must be individually tailored for this patient population. A
      multidisciplinary team approach is best with preoperative nutritional assessment
      and pulmonary evaluation.

PMID- 22389790
TI  - Potential contributors to the canadian pediatric obesity epidemic.
AB  - As a group, Canadian children and youth are heavier than at any time in the
      recent past. However, to date there has been no critical examination of the
      factors which are likely to have contributed to these deleterious trends. A
      review of the evidence suggests that there is robust evidence supporting the role
      of reduced sleep, increased sedentary time, increased consumption of sugar
      sweetened beverages, and secular increases in adult obesity as contributing
      factors to the current epidemic of childhood obesity. There is moderate evidence
      that these trends are related to changes in either total energy intake or
      physical activity, while there is very little evidence supporting the role of
      maternal age, breastfeeding, exposure to endocrine disrupters, or inadequate
      calcium intake. These findings suggest that targeting sleep, sedentary time, and
      sugar-sweetened beverage intake in Canadian children and youth may help to
      prevent future weight gain at the population level.

PMID- 22389793
TI  - Esophageal involvement in scleroderma: clinical, endoscopic, and manometric
      features.
AB  - Aim. To evaluate characteristics of esophageal involvement in scleroderma.
      Methods. The study was prospective and concerned 194 patients with a definite
      systemic sclerosis. Gastroesophageal endoscopy and esophageal manometry were
      performed in all the cases. Results. Symptoms were present in 118 cases (60.8%);
      they were signs of GERD or dysphagia, respectively, in 94 (48.4%) and 91 patients
      (46.9%). Reflux esophagitis was found in 73 cases (37.6%); it was mild or
      moderate in 47 cases (24.2%) and severe or complicated in the remaining cases.
      Manometry revealed a lower esophageal sphincter incompetence and esophageal motor
      disorders, respectively, in 118 (60.8%) and 157 cases (80.9%). Presence of these
      late was not related to age, duration, or skin extension of the disease, but with
      clinical complaint and/or mucosal damage. Conclusion. Esophageal involvement is
      frequent during scleroderma. Manometry is the most sensible examination and could
      be a screening procedure.

PMID- 22389794
TI  - Measures of rheumatoid arthritis disease activity in Australian clinical
      practice.
AB  - Objectives. To investigate which rheumatoid arthritis (RA) disease activity
      measures are being collected in patients receiving glucocorticoids, non-biologic
      or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian
      rheumatology practice. Methods. A retrospective audit of medical records was
      conducted from eight rheumatology practices around Australia. Each rheumatologist
      recruited 30 consecutive eligible patients into the review, 10 of whom must have
      been receiving a biological agent for rheumatoid arthritis. Disease activity
      measures and radiographic assessments were collected from each patient's last
      consultation. For biologic patients, disease activity measures were also
      collected from when the patient was first initiated on the biological agent.
      Results. At last consultation, the disease measures that were recorded most often
      were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently
      recorded (16.3%). The rate of recording disease activity measures for patients
      receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This
      review has shown inconsistency of RA activity measures being recorded in
      Australian rheumatology clinical practice. An accurate assessment of the disease
      process is necessary to effectively target rheumatoid arthritis patients to treat
      in order to achieve optimal outcomes.

PMID- 22389795
TI  - Patient preference assessment reveals disease aspects not covered by recommended
      outcomes in polymyositis and dermatomyositis.
AB  - Objectives. Polymyositis (PM) and dermatomyositis (DM) are characterized by
      impaired muscle function with a majority of patients developing sustained
      disability. The aim of this study was to evaluate the patient's individual
      priorities (patient preference) of disabilities most important to improve in
      PM/DM using the MacMaster Toronto Arthritis Patient Preference Disability
      Questionnaire (MACTAR), to correlate the MACTAR to myositis outcomes and to
      evaluate its test-retest reliability. Methods. Twenty-eight patients with PM/DM
      performed recommended outcomes as well as the MACTAR, which was performed twice
      with one week apart. Results. Sexual activity, walking, biking, social
      activities, and sleep constituted the predominating disabilities. Seventy-two and
      33% of the identified disabilities were not covered by items of the Health
      Assessment Questionnaire and the Myositis Activities Profile. Correlations
      between the MACTAR and health-related quality of life measures were r(s) = -0.67
      0.73, correlations with measures of activities of daily living and participation
      in society were r(s) = 0.51-0.60 with lower correlations for other outcomes.
      Intraclass correlation (ICC) and weighted Kappa (K(w)) coefficients were 0.83 and
      0.68, respectively, for test-retest reliability of the MACTAR. Conclusions. The
      MACTAR interview had promising measurement properties and identified patient
      preference disabilities in PM/DM that were not covered by recommended outcomes.

PMID- 22389796
TI  - The Performance of Quantiferon TB Gold In-Tube as a Screening Tool in Paediatric
      Rheumatology prior to Initiation of Infliximab: A Single Centre's Experience.
AB  - Background. Patients with autoimmune diseases and latent tuberculosis infection
      (LTBI) are at risk of developing catastrophic tuberculosis disease following
      infliximab treatment. Quantiferon-TB gold in-Tube (QTB) has proven a more
      accurate screening tool than tuberculin skin test (TST) in adult populations.
      Objectives. To assess the utility and validity of QTB in children, prior to
      treatment with infliximab. Methods. Retrospective cohort of patients started on
      infliximab following endorsement of QTB as a screening tool by the NICE
      guidelines in 2006. Results. Twenty three patients (12 females and 11 males) were
      included in the study. A chest radiograph (CXR) and QTB was performed prior to
      starting infliximab. Fourteen patients had a recorded negative TST result. One
      patient had a positive QTB while two had indeterminate results. Their CXRs were
      not suggestive of TB and TSTs were negative. The patients with indeterminate
      results were started on infliximab and had regular clinical assessment for TB
      disease. Repeat QTB was negative in one while remained indeterminate in the
      other. None of our 23 patients developed TB. Conclusion. QTB is a useful screen
      tool for LTBI. Indeterminate results warrant careful assessment and re
      evaluation, but should not preclude from initiation of anti TNF treatment.

PMID- 22389798
TI  - Wegener's granulomatosis presenting with pachymeningitis: clinical and imaging
      remission by rituximab.
AB  - A 27-year-old woman was admitted for intractable right-sided neck, ear, and jaw
      pain with gradual development of tinnitus and hearing loss. A cerebral MRI showed
      meningo-dural enhancement, and additional diagnostic workup revealed a right
      pulmonary infiltrate and positive PR-3 ANCA. Biopsies from nasal mucosa and lung
      showed chronic inflammation with granuloma formation. Based on these findings the
      patient was diagnosed with Wegener's granulomatosis with pachymeningitis. There
      was no clinical response to oral Prednisolone and Cyclophosphamide, but complete
      clinical and imaging remission was achieved by adding Rituximab.

PMID- 22389797
TI  - Results of a Pilot Randomized Placebo-Controlled Trial in Primary and Secondary
      Raynaud's Phenomenon with St. John's Wort: Detecting Changes in Angiogenic
      Cytokines When RP Improves.
AB  - Objectives.To perform a 6-week double-blind RCT in Raynaud's phenomenon (RP)
      comparing the plant extract St. John's Wort (SJW) to placebo. Methods. RP
      patients having at least 7 attacks per week were stratified by primary and
      secondary RP and within secondary by systemic sclerosis or other connective
      tissue disease. Subjects completed a daily standardized diary recording all RP
      attacks (frequency, duration and severity). Serum levels of 18 inflammatory and
      angiogenic cytokines were measured pre- and post-treatment. Results. Eighteen
      patients completed the study; 8 received SJW and 10 placebo. The decrease in mean
      number of attacks per day was 0.75 with SJW and 1.01 with placebo, P = 0.06.
      Attack duration and severity were not different between groups. Cytokine analyses
      demonstrated no between-groups differences. Combining treatment groups, those
      with >50% improvement in frequency of attacks yielded a significant increase in E
      selectin (P = 0.049), MMP-9 (P = 0.011), G-CSF (P = 0.02), and VEGF (P = 0.012)
      pre- versus post-treatment. A >=50% improvement in severity of attacks
      corresponded to a significant increase in levels of sVCAM-1 (P = 0.003), sICAM-1
      (P = 0.007), and MCP-1 (P = 0.004). Conclusions. There were no clinical or
      biomarker benefit of SJW versus placebo in RP. However, combining all patients,
      there were changes in some cytokines that may be further investigated.

PMID- 22389799
TI  - Pericarditis revealing large vessel vasculitis.
AB  - Large vessels vasculitis and more specifically, Giant cell arteritis, is
      characterized by increased inflammatory markers, headaches and altered clinical
      status. Diagnosis is confirmed by biopsy of temporal arteries showing the
      presence of granuloma and vasculitis. We hereby report the case of a patient
      presenting initially as pericarditis and revealing large vessel vasculitis using
      FDG-PET.

PMID- 22389800
TI  - Osteoporosis and bisphosphonate-related osteonecrosis of the jaw bone.
AB  - The aim of this longitudinal study is to present data from 76 female patients
      treated with bisphosphonates (BPs) for postmenopausal osteoporosis and referred
      to the Unit of Oral Diagnosis and Day Surgery of the University of Milano for
      diagnosis and treatment. All patients received a thorough oral examination. The
      diagnosis of osteonecrosis of the jaw bone (ONJ) was made from radiographic and
      clinical findings. 9% of individuals had BRONJ at first visit. Patients with
      dental or periodontal abscess were significantly more likely to develop BRONJ
      (OR: 2.9, 95% CI 0.5-15.9). Patients with osteoporosis receiving BPs may develop
      BRONJ, especially in the presence of an active infectious process in the mouth.
      Clinicians should carefully follow up on individuals receiving bisphosphonates
      therapy to avoid the occurrence of osteonecrotic lesions.

PMID- 22389801
TI  - Clinical and ultrasound examination of the leeds enthesitis index in psoriatic
      arthritis and rheumatoid arthritis.
AB  - Objective. To compare scores for the Leeds enthesitis index in psoriatic
      arthritis and rheumatoid arthritis using clinical assessment and ultrasonography
      (US). Design. Swelling and tenderness of the enthesis was assessed at six sites:
      lateral epicondyles of humerus (LE), medial condyles of femur (MC), and the
      insertion of the Achilles tendon (AT). US assessed "inflammatory activity" (power
      Doppler signal, oedema, tendon thickening, and bursal swelling) and "damage"
      (erosions and enthesophytes). Results. 94 patients were included, 71 with PsA and
      23 with RA. The patients with RA were significantly older (PsA 47.6 years; RA
      62.6 years; (mean difference in ages =15.0 years, 95% CI 9.3-20.7 years)). US
      scores were higher in RA at the LE, significantly so for the "damage" scores. No
      differences between RA and PsA were seen at the other sites. As a result, the
      odds ratio for PsA, given an US score above the median, was 0.41 (0.13-1.03).
      However, using the clinical score, the odds ratio for PsA was 2.16 (0.81-5.70).
      Conclusions. Although clinical scores of enthesitis are greater in PsA compared
      to RA, US enthesitis scores did not distinguish between RA and PsA. This may in
      part be due to more frequent juxta-articular involvement in RA and in part due to
      the older age of the subjects with RA.

PMID- 22389802
TI  - The contribution of four immunogenetic markers for predicting persistent activity
      in patients with recent-onset rheumatoid arthritis or undifferentiated arthritis.
AB  - We assessed the contribution of four baseline markers-HLA-DRB1 shared epitope
      (SE), -308 tumor necrosis factor alpha gene promoter polymorphism, rheumatoid
      factor, and anticitrullinated peptide antibodies-for predicting persistent
      activity (DAS28 score >=2.6) after one year of followup in a cohort of 201
      patients with recent-onset rheumatoid arthritis (RA) or undifferentiated
      arthritis (UA) aged 16 years or older who had a 4-week to 12-month history of
      swelling of at least two joints. Patients had not been previously treated with
      corticosteroids or disease-modifying antirheumatic drugs (DMARD). In the best
      logistic regression model, only two variables were retained: SE positivity and
      number of DMARD administered (area under the curve = 76.4%; 95% CI: 69.2%, 84.4%;
      P < 0.001). The best linear regression model also included these two variables,
      explaining only 22.5% of the variability of DAS28 score. In this study, given an
      equal number of DMARD administered, the probability of persistent activity in
      patients with recent-onset RA or UA was significantly influenced by SE presence.

PMID- 22389803
TI  - Assessment of panoramic radiomorphometric indices of the mandible in a brazilian
      population.
AB  - The aim of this study was to evaluate radiomorphometric indices in dental
      panoramic radiographs in order to identify possible interrelationships between
      these indices and the sex and age of the patients analyzed. The study included
      1287 digital panoramic radiographic images of patients that were grouped into
      five age groups (1 = age 17-20; 2 = age 21-35; 3 = age 36-55; 4 = age 56-69; 5 =
      over age 70). Two indices-cortical width at the gonion (GI) and below the mental
      foramen (MI)-were measured bilaterally in all panoramic radiographs. Statistical
      analysis was performed with Kruskal-Wallis and Mann-Whitney tests (alpha = 0.05).
      Results for the indices measurements showed significant differences among patient
      age groups of both sexes, considering that groups 4 and 5 presented lower values
      for the cortical width of both indices. The present paper supports the role of
      sex- and age-related changes in mandibular radiomorphometric indices in
      identifying skeletal osteopenia.

PMID- 22389804
TI  - Medical student identification of knee effusion by ultrasound.
AB  - Twenty-one fourth-year medical students were given a brief lecture on ultrasound
      of the knee and fifteen minutes of supervised ultrasound scanning of three
      cadavers which had been injected with saline to give varying degrees of knee
      effusions. Each student was then individually observed and required to scan both
      knees of a cadaver different from the practice cadavers and identify the patella,
      the femur, the quadriceps tendon and if a suprapatellar effusion was present, and
      which knee had the larger effusion. All twenty-one students correctly identified
      all anatomical structures, suprapatellar effusions, and which knee had the larger
      effusion. Identifying a knee effusion can be an important clinical finding in
      diagnosing and managing a patient with knee complaints. Fourth-year medical
      students can learn to identify knee effusions with ultrasound following a brief
      introductory lecture and hands-on scanning practice session.

PMID- 22389805
TI  - Recommendations for Diagnosis and Management of Osteoporosis in COPD Men.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are at increased risk
      for osteoporosis and fractures because of lifestyle factors, systemic effects of
      the disease, side effects of treatment, and comorbidities. The initial evaluation
      of COPD men for osteoporosis must include a detailed medical history and physical
      examination, assessment of COPD severity, and additional tests, as suggested by
      results of clinical evaluation. Osteoporosis is diagnosed on the basis of bone
      mineral density (BMD) measurement with DEXA of the lumbar spine and hip, but
      fracture risk assessments tools, as FRAX, could be used as useful supplements to
      BMD assessments for therapeutics interventions. The prevention and treatment of
      osteoporosis in COPD involves nonpharmacologic and pharmacologic measures, as
      lifestyle measures and nutritional recommendations, management of COPD treatment
      (based on the use of limited corticosteroids doses), and drug therapy
      (bisphosphonates, teriparatide). In this paper, the current recommendations for
      diagnosis and management of osteoporosis in COPD men, based on recent medical
      bibliography, are presented and discussed.

PMID- 22389806
TI  - High dose infliximab in the treatment of refractory uveitis: does dose matter?
AB  - Background. Infliximab (INF) has been shown to be beneficial in treating
      refractory uveitis, however, no data exist on optimal dosing and the efficacy of
      higher dosing. Objectives. To compare the efficacy of low-dose (LD) (<10 mg/kg),
      moderate-dose (MD) (>=10-15 mg/kg), and high-dose (HD) INF (>=15-20 mg/kg) in the
      treatment of uveitis. Methods. Retrospective chart review children with uveitis
      diagnosed at Childrens Hospital Los Angeles and Millers Children's Hospital, CA,
      USA. Results. Of the 34 INF-treated children, 6 patients received LD, 19 received
      MD, and 9 received HD. Average disease duration prior to therapy was 10.6, 24.6,
      and 37.1 months each group, respectively. Topical steroids were discontinued
      after an average of 3 months, 9.5 months, and 10.2 months in the LD, MD, and HD
      groups, respectively. We found that 66% of patients receiving LD, 42% of MD, and
      66% receiving HD INF failed therapy and required either dose escalation or
      alternate medication for disease control. Conclusions. INF is beneficial in the
      treatment of uveitis, and dose escalation up to 4 times above the approved dose
      is often necessary to achieve disease control in patients with uveitis. Doses <
      10 mg/kg every 4 weeks may not be sufficient to control disease.

PMID- 22389807
TI  - Visual Puzzles, Figure Weights, and Cancellation: Some Preliminary Hypotheses on
      the Functional and Neural Substrates of These Three New WAIS-IV Subtests.
AB  - In this study, five consecutive patients with focal strokes and/or cortical
      excisions were examined with the Wechsler Adult Intelligence Scale and Wechsler
      Memory Scale-Fourth Editions along with a comprehensive battery of other
      neuropsychological tasks. All five of the lesions were large and typically
      involved frontal, temporal, and/or parietal lobes and were lateralized to one
      hemisphere. The clinical case method was used to determine the cognitive
      neuropsychological correlates of mental rotation (Visual Puzzles), Piagetian
      balance beam (Figure Weights), and visual search (Cancellation) tasks. The
      pattern of results on Visual Puzzles and Figure Weights suggested that both
      subtests involve predominately right frontoparietal networks involved in visual
      working memory. It appeared that Visual Puzzles could also critically rely on the
      integrity of the left temporoparietal junction. The left temporoparietal junction
      could be involved in temporal ordering and integration of local elements into a
      nonverbal gestalt. In contrast, the Figure Weights task appears to critically
      involve the right temporoparietal junction involved in numerical magnitude
      estimation. Cancellation was sensitive to left frontotemporal lesions and not
      right posterior parietal lesions typical of other visual search tasks. In
      addition, the Cancellation subtest was sensitive to verbal search strategies and
      perhaps object-based attention demands, thereby constituting a unique task in
      comparison with previous visual search tasks.

PMID- 22389808
TI  - Is MS Intention Tremor Amplitude Related to Changed Peripheral Reflexes?
AB  - Intention tremor is related to lesions in the cerebellum or connected pathways.
      Intention tremor amplitude decreased after peripheral arm cooling in patients
      with multiple sclerosis (MS), likely caused by a reduction of muscle spindle
      afferent inflow, while amplitude increased when muscle spindles were artificially
      stimulated by tendon vibration. This study investigated the contribution of
      peripheral reflexes to the generation of MS intention tremor. Tendon reflexes of
      biceps, triceps, and brachioradialis, muscles were measured, using an
      electromechanical triggered reflex hammer. MS patients with (n = 17) and without
      (n = 17) upper limb intention and 18 healthy controls were tested. Latency of
      brachioradialis, biceps, and triceps tendon reflexes was greater in MS patients
      with tremor than in healthy controls and MS patients without tremor (except for
      the triceps reflex). Peak and peak-to-peak amplitude were not different between
      groups. It is concluded that tendon reflexes were delayed but not enlarged in MS
      patients with tremor.

PMID- 22389809
TI  - Apathy and anhedonia in Parkinson's disease.
AB  - Depression, apathy, and anhedonia are often comorbid in patients with Parkinson's
      disease. Since the morbid states of apathy and anhedonia are complicated, these
      symptoms are often difficult to diagnose. Several therapeutic methods for apathy
      and anhedonia are considered effective. However, the validity of these methods
      has not been established. Similar to depression, apathy and anhedonia clearly
      affect the quality of life of patients and their families. Therefore, accurate
      diagnoses of morbid states in the early stage of the disease and corresponding
      appropriate treatments should be given high priority.

PMID- 22389810
TI  - Perceived changes in communicative interaction in atypical parkinsonism.
AB  - The aim of this study was to examine if atypical parkinsonism affects the
      communicative ability in conversational interaction. Fifteen persons close to
      individuals with atypical parkinsonism answered a questionnaire, "Assessment of
      Change in Communicative Interaction" (ACCI), estimating perceived change in
      interactive skills compared to before the onset of the disease. The study also
      examined if perceived change correlated with disease duration. The results showed
      that at group level, the participants experienced change in many aspects of
      conversational interaction, particularly regarding the affected person's speech,
      body communication, response latency, phrase length, word finding, and ability to
      make themselves understood. There was no correlation between perceived change and
      disease duration. In conclusion, results indicated that the communicative
      interaction of individuals with atypical parkinsonism is significantly affected
      and that information elicited from significant others can help define specific
      problem areas or foci of concern that need to be targeted in communicative
      intervention or at least considered in interaction with these persons.

PMID- 22389811
TI  - Identification of potential drug targets implicated in Parkinson's disease from
      human genome: insights of using fused domains in hypothetical proteins as probes.
AB  - High-throughput genome sequencing has led to data explosion in sequence
      databanks, with an imbalance of sequence-structure-function relationships,
      resulting in a substantial fraction of proteins known as hypothetical proteins.
      Functions of such proteins can be assigned based on the analysis and
      characterization of the domains that they are made up of. Domains are basic
      evolutionary units of proteins and most proteins contain multiple domains. A
      subset of multidomain proteins is fused domains (overlapping domains), wherein
      sequence overlaps between two or more domains occur. These fused domains are a
      result of gene fusion events and their implication in diseases is well
      established. Hence, an attempt has been made in this paper to identify the fused
      domain containing hypothetical proteins from human genome homologous to
      parkinsonian targets present in KEGG database. The results of this research
      identified 18 hypothetical proteins, with domains fused with ubiquitin domains
      and having homology with targets present in parkinsonian pathway.

PMID- 22389812
TI  - HRQOLISP-26: A Concise, Multiculturally Valid, Multidimensional, Flexible, and
      Reliable Stroke-Specific Measure.
AB  - Background. A multidimensional, brief, and flexible stroke-specific health
      related quality of life (HRQOL) measure is still needed. The aim was to develop a
      shortened version of the HRQOLISP-102, a multiculturally generated measure with
      excellent psychometric properties. Methods. Participants included 100 (Ibadan,
      Nigeria) and 103 (Berlin, Germany) stroke patients compared to 100 (Ibadan) and
      50 (Berlin) apparently healthy adults. Using standard protocol, the 26-item
      version was generated, consisting of therapeutically relevant physical,
      psychological, cognitive, and ecosocial domains. Criterion validity of the
      HRQOLISP-26 was determined using Bland-Altman statistics. "Known groups" validity
      was assessed using NIHSS, stroke levity score, and modified Rankin scale.
      Results. HRQOLISP-26 was easily interpretable and precise with no significant
      floor/ceiling effect. It can be completed within 7 minutes. It showed good
      content, construct, "known groups," and criterion validity. It demonstrated good
      internal consistency (alpha = 0.81, 0.89) and test-retest reliability.
      Conclusions. HRQOLISP-26 is novel, brief, multiculturally-valid, and flexible for
      routine assessment of HRQOL in stroke patients.

PMID- 22389814
TI  - Embodying Emotional Disorders: New Hypotheses about Possible Emotional
      Consequences of Motor Disorders in Parkinson's Disease and Tourette's Syndrome.
AB  - Parkinson's disease (PD) and Tourette's syndrome (TS) lead to important motor
      disorders among patients such as possible facial amimia in PD and tics in
      Tourette's syndrome. Under the grounded cognition framework that shows the
      importance of motor embodiment in emotional feeling (Niedenthal, 2007), both
      types of pathology with motor symptoms should be sufficient to induce potential
      impairments for these patients when recognizing emotional facial expressions
      (EFE). In this opinion paper, we describe a theoretical framework that assumes
      potential emotional disorders in Parkinson's disease and Tourette's syndrome
      based on motor disorders characterizing these two pathologies. We also review
      different methodological barriers in previous experimental designs that could
      enable the identification of emotional facial expressions despite emotional
      disorders in PD and TS.

PMID- 22389813
TI  - Mechanisms of brain aging regulation by insulin: implications for
      neurodegeneration in late-onset Alzheimer's disease.
AB  - Insulin and IGF seem to be important players in modulating brain aging. Neurons
      share more similarities with islet cells than any other human cell type. Insulin
      and insulin receptors are diffusely found in the brain, especially so in the
      hippocampus. Caloric restriction decreases insulin resistance, and it is the only
      proven mechanism to expand lifespan. Conversely, insulin resistance increases
      with age, obesity, and sedentarism, all of which have been shown to be risk
      factors for late-onset Alzheimer's disease (AD). Hyperphagia and obesity
      potentiate the production of oxidative reactive species (ROS), and chronic
      hyperglycemia accelerates the formation of advanced glucose end products (AGEs)
      in (pre)diabetes-both mechanisms favoring a neurodegenerative milieu. Prolonged
      high cerebral insulin concentrations cause microvascular endothelium
      proliferation, chronic hypoperfusion, and energy deficit, triggering beta-amyloid
      oligomerization and tau hyperphosphorylation. Insulin-degrading enzyme (IDE)
      seems to be the main mechanism in clearing beta-amyloid from the brain.
      Hyperinsulinemic states may deviate IDE utilization towards insulin processing,
      decreasing beta-amyloid degradation.

PMID- 22389815
TI  - Mgat5 deficiency in T cells and experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative
      disease initiated by autoreactive T cells. Mgat5, a gene in the Asn (N-) linked
      protein glycosylation pathway, associates with MS severity and negatively
      regulates experimental autoimmune encephalomyelitis (EAE) and spontaneous
      inflammatory demyelination in mice. N-glycan branching by Mgat5 regulates
      interaction of surface glycoproteins with galectins, forming a molecular lattice
      that differentially controls the concentration of surface glycoproteins. T-cell
      receptor signaling, T-cell proliferation, T(H)1 differentiation, and CTLA-4
      endocytosis are inhibited by Mgat5 branching. Non-T cells also contribute to MS
      pathogenesis and express abundant Mgat5 branched N-glycans. Here we explore
      whether Mgat5 deficiency in myelin-reactive T cells is sufficient to promote
      demyelinating disease. Adoptive transfer of myelin-reactive Mgat5(-/-) T cells
      into Mgat5(+/+) versus Mgat5(-/-) recipients revealed more severe EAE in the
      latter, suggesting that Mgat5 branching deficiency in recipient naive T cells
      and/or non-T cells contribute to disease pathogenesis.

PMID- 22389817
TI  - Dural arteriovenous fistulas in the cavernous sinus: clinical research and
      treatment.
AB  - Introduction. The purpose of this paper is to clarify the clinical course, with
      the dural carotid cavernous fistula (CCF), featuring a pallet of symptoms, paying
      special attention to radiological findings. Methods. Seventy-six consecutive
      patients with dural CCFs were investigated in detail, all of whom were defined by
      angiography. Results. The most common initial symptom was diplopia in 47 patients
      (62%) and the most frequently observed on arrival were type II, featuring cranial
      nerve palsies followed by the classical triad in 27, and then type I only with
      cranial nerve palsies. The time until admission with type I (mean: 6.7 W +/- 6.0)
      was significantly shorter than that with type II (mean: 25.1 W +/- 23.5).
      Branches from bilateral carotid arteries widely inflowing into bilateral carotid
      cavernous sinus were present in 30 (39%), 20 (26%) of which also demonstrated
      direct inflow into the intercavernous sinus. type I and II had more multiple
      venous drainage routes as compared with type III (classical triad only on
      arrival) and IV (initial development of the classical triad followed by cranial
      nerve palsy). Conclusion. In our series of dural CCF patients, the most common
      initial symptom was cranial nerve palsy, mostly featuring multiple venous
      drainage including cortical drainage. Such palsies should be added to the
      classical triad as indicative symptoms. Bilateral carotid arteries often inflow
      into cavernous and intercavernous sinuses, which should be taken into account in
      choice of therapeutic strategy.

PMID- 22389818
TI  - Cervical spondylotic myelopathy: pathophysiology, diagnosis, and surgical
      techniques.
AB  - Cervical spondylotic myelopathy is a degenerative spinal disease which may lead
      to significant clinical morbidity. The onset of symptoms is usually insidious,
      with long periods of fixed disability and episodic worsening events. Regarding
      the pathophysiology of CSM, the repeated injuries to the spinal cord are caused
      by both static and dynamic mechanical factors. The combination of these factors
      affects the spinal cord basically through both direct trauma and ischemia.
      Regarding the diagnosis, both static and dynamics X-rays, as well as magnetic
      resonance imaging are important for preoperative evaluation as well as
      individualizing surgical planning. The choice of the most appropriate technique
      is affected by patient's clinical condition radiologic findings, as well as
      surgeon's experience. In opposition to the old belief that patients presenting
      mild myelopathy should be treated conservatively, there has progressively been
      amount of evidence indicating that the clinical course of this disease is
      progressive deterioration and that early surgical intervention improves long-term
      functional recovery and neurological prognosis.

PMID- 22389819
TI  - Penicillamine neurotoxicity: an hypothesis.
AB  - Penicillamine, dimethyl cysteine, thiovaline, remains the drug of choice for the
      treatment of patience with Wilson disease. It is also of value in the treatment
      of cysteinuria and rheumatoid arthritis, it has also been suggested that it has
      value in the management of other rare diseases. It also has multiple toxicities.
      The majority of these can be explained as chemical toxicity, for instance its
      weak antipyridoxine action and its ability to interfere with lysyloxidea
      resulting in skin lesions. More important are its ability to induce immune
      reactions such as SLE, immune complex nephritis, the Ehlers Danlos syndrome and
      Goodpasture's syndrome. However the sudden increase in neurological signs which
      may occur in a small number of patients remains unexplained. The theory is
      proposed that this is due to lethal synthesis. In susceptible patients the-SH
      radical is liberated from penicillamine and will inhibit-SH dependent enzymes in
      the Krebs cycle leading to death in neurones. Other toxic metabolites may also be
      produced such as methyl mercaptan and ethyl mercaptan either of which could
      produce a similar metabolic block.

PMID- 22389820
TI  - Herpes encephalitis masquerading as tumor.
AB  - A 54 year old lady presented with lethargy and 15 kg weight loss over the past
      year. CT scan of the head revealed left temporal lobe hypodensity with a discrete
      area of hemorrhage within the left mesial temporal lobe. Due to concerns about
      impending central herniation, lumbar puncture was not performed. MRI of the brain
      showed a large lesion of the left temporal lobe, extending to the left frontal
      lobe, and very patchy meningeal enhancement. There was a noncontiguous lesion of
      the right insula. A differential diagnosis of herpes simplex encephalitis (HSE)
      and multifocal infiltrative glioma was entertained. MR spectroscopy demonstrated
      an increased choline peak at the level of the medial left temporal lobe and MR
      perfusion demonstrated patchy areas of hyperperfusion within the left anterior
      temporal lobe, both suggestive of neoplastic disease. Following open brain
      biopsy, pathology revealed herpes simplex virus (HSV) positive nuclei in the
      cortex and subcortical white matter. As both herpes simplex encephalitis and low
      grade glioma demontrate MRI findings of hypointensity on T1 images and
      hyperintensity on T2 images, the diagnosis of herpes encephalitis can be clouded
      by confounding factors, especially when cerebrospinal fluid (CSF) cannot be
      obtained.

PMID- 22389816
TI  - The Fox and the Rabbits-Environmental Variables and Population Genetics (1)
      Replication Problems in Association Studies and the Untapped Power of GWAS (2)
      Vitamin A Deficiency, Herpes Simplex Reactivation and Other Causes of Alzheimer's
      Disease.
AB  - Classical population genetics shows that varying permutations of genes and risk
      factors permit or disallow the effects of causative agents, depending on
      circumstance. For example, genes and environment determine whether a fox kills
      black or white rabbits on snow or black ash covered islands. Risk promoting
      effects are different on each island, but obscured by meta-analysis or GWAS data
      from both islands, unless partitioned by different contributory factors. In
      Alzheimer's disease, the foxes appear to be herpes, borrelia or chlamydial
      infection, hypercholesterolemia, hyperhomocysteinaemia, diabetes, cerebral
      hypoperfusion, oestrogen depletion, or vitamin A deficiency, all of which promote
      beta-amyloid deposition in animal models-without the aid of gene variants. All
      relate to risk factors and subsets of susceptibility genes, which condition their
      effects. All are less prevalent in convents, where nuns appear less susceptible
      to the ravages of ageing. Antagonism of the antimicrobial properties of beta
      amyloid by Abeta autoantibodies in the ageing population, likely generated by
      antibodies raised to beta-amyloid/pathogen protein homologues, may play a role in
      this scenario. These agents are treatable by diet and drugs, vitamin
      supplementation, pathogen detection and elimination, and autoantibody removal,
      although again, the beneficial effects of individual treatments may be tempered
      by genes and environment.

PMID- 22389822
TI  - The ABCD and ABCD2 Scores and the Risk of Stroke following a TIA: A Narrative
      Review.
AB  - The California, ABCD, and ABCD2 risk scores (ABCD system) were developed to help
      stratify short-term stroke risk in patients with TIA (transient ischemic attack).
      Beyond this scope, the ABCD system has been extensively used to study other
      prognostic information such as DWI (diffusion-weighted imaging) abnormalities,
      large artery stenosis, atrial fibrillation and its diagnostic accuracy in TIA
      patients, which are independent predictors of subsequent stroke in TIA patients.
      Our comprehensive paper suggested that all scores have and equivalent prognostic
      value in predicting short-term risk of stroke; however, the ABCD2 score is being
      predominantly used at most centers. The majority of studies have shown that more
      than half of the strokes in the first 90 days, occur in the first 7 days. The
      majority of patients studied were predominantly classified to have a higher
      ABCD/ABCD2 > 3 scores and were particularly at a higher short-term risk of stroke
      or TIA and other vascular events. However, patients with low risk ABCD2 score < 4
      may have high-risk prognostic indicators, such as diffusion weighted imaging
      (DWI) abnormalities, large artery atherosclerosis (LAA), and atrial fibrillation
      (AF). The prognostic value of these scores improved if used in conjunction with
      clinical information, vascular imaging data, and brain imaging data. Before more
      data become available, the diagnostic value of these scores, its applicability in
      triaging patients, and its use in evaluating long-term prognosis are rather
      secondary; thus, indicating that the primary significance of these scores is for
      short-term prognostic purposes.

PMID- 22389821
TI  - Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of
      LPS Induced the Inflammatory Process along with the Selective Degeneration of
      Nigrostriatal Dopaminergic Neurons.
AB  - We have developed an animal model of degeneration of the nigrostriatal
      dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD).
      The implication of neuroinflammation on this disease was originally established
      in 1988, when the presence of activated microglia in the substantia nigra (SN) of
      parkinsonians was reported by McGeer et al. Neuroinflammation could be involved
      in the progression of the disease or even has more direct implications. We
      injected 2 MUg of the potent proinflammatory compound lipopolysaccharide (LPS) in
      different areas of the CNS, finding that SN displayed the highest inflammatory
      response and that dopaminergic (body) neurons showed a special and specific
      sensitivity to this process with the induction of selective dopaminergic
      degeneration. Neurodegeneration is induced by inflammation since it is prevented
      by anti-inflammatory compounds. The special sensitivity of dopaminergic neurons
      seems to be related to the endogenous dopaminergic content, since it is overcome
      by dopamine depletion. Compounds that activate microglia or induce inflammation
      have similar effects to LPS. This model suggest that inflammation is an important
      component of the degeneration of the nigrostriatal dopaminergic system, probably
      also in PD. Anti-inflammatory treatments could be useful to prevent or slow down
      the rate of dopaminergic degeneration in this disease.

PMID- 22389825
TI  - Safety and Efficacy of Thrombolytic Therapy Using rt-PA (Alteplase) in Acute
      Ischemic Stroke.
AB  - The aim of this study was to evaluate the efficacy and safety of thrombolytic
      therapy. Our study enrolled 23 patients out of which 2 patients died due to ICH;
      we also found that only 39% of patients reached hospital within stroke window,
      and for those treated, mean NIHSS during admission was 14.0, but drastic
      improvement was shown after 24 hours of treatment, that is, 9.89 (P < 0.0001),
      and at discharge, it was 5.1 (P < 0.0001) which showed a clear impact of the
      treatment, and around 60% of patients were discharged within an mRS score of 1
      and 2. Hence, it was found that thrombolytic therapy was beneficial, efficacious,
      and safe if used within 3 to 4.5 hours.

PMID- 22389823
TI  - Familial Parkinson's Disease Mutant E46K alpha-Synuclein Localizes to Membranous
      Structures, Forms Aggregates, and Induces Toxicity in Yeast Models.
AB  - In Parkinson's disease (PD), midbrain dopaminergic neuronal death is linked to
      the accumulation of aggregated alpha-synuclein. The familial PD mutant form of
      alpha-synuclein, E46K, has not been thoroughly evaluated yet in an organismal
      model system. Here, we report that E46K resembled wild-type (WT) alpha-synuclein
      in Saccharomyces cerevisiae in that it predominantly localized to the plasma
      membrane, and it did not induce significant toxicity or accumulation. In
      contrast, in Schizosaccharomyces pombe, E46K did not associate with the plasma
      membrane. Instead, in one strain, it extensively aggregated in the cytoplasm and
      was as toxic as WT. Remarkably, in another strain, E46K extensively associated
      with the endomembrane system and was more toxic than WT. Our studies recapitulate
      and extend aggregation and phospholipid membrane association properties of E46K
      previously observed in vitro and cell culture. Furthermore, it supports the
      notion that E46K generates toxicity partly due to increased association with
      endomembrane systems within cells.

PMID- 22389824
TI  - Ion channels in glioblastoma.
AB  - Glioblastoma is the most common primary brain tumor with the most dismal
      prognosis. It is characterized by extensive invasion, migration, and
      angiogenesis. Median survival is only 15 months due to this behavior, rendering
      focal surgical resection ineffective and adequate radiotherapy impossible. At
      this moment, several ion channels have been implicated in glioblastoma
      proliferation, migration, and invasion. This paper summarizes studies on
      potassium, sodium, chloride, and calcium channels of glioblastoma. It provides an
      up-to-date overview of the literature that could ultimately lead to new
      therapeutic targets.

PMID- 22389826
TI  - Patients with severe poststroke fatigue show a psychosocial profile comparable to
      patients with other chronic disease: implications for diagnosis and treatment.
AB  - Objective. To obtain a psychosocial profile of patients with poststroke fatigue
      (PSF), which could aid in optimizing treatment strategies. Methods. Eighty-eight
      outpatients with severe PSF measured with the Checklist Individual Strength
      fatigue subscale (CIS-f) and the Fatigue Severity Scale (FSS) were selected.
      Depression and anxiety, psychological distress, coping, social support, and self
      efficacy of this group were compared to reference groups of healthy controls and
      patients with other chronic diseases. Associations between psychosocial
      characteristics and fatigue were calculated. Results. Compared to healthy
      controls, patients with PSF reported more psychological distress, less problem
      focused coping, and more positive social support. Minor or no differences were
      found in comparison with other chronic patients. The CIS-f correlated with
      somatic complaints and the FSS with cognitive complaints. Conclusion. Patients
      with PSF show a psychosocial profile comparable to patients with other chronic
      disease. Implications for diagnosis and treatment are discussed.

PMID- 22389827
TI  - Effects of 6-month, Multimodal Exercise Program on Clinical and Gait Parameters
      of Patients with Idiopathic Parkinson's Disease: A Pilot Study.
AB  - This pilot study aimed to identify the effects of a 6-month, multimodal exercise
      program on clinical and gait parameters in patients with Parkinson's disease. Two
      groups of participants were enrolled in the study: Trained Group (TG) and Control
      Group (CG). Individuals in the TG exercised three times a week for 24 weeks (in a
      multimodal exercise program), while the CG participants maintained their regular
      activity level. Participants in both the TG and the CG were assessed at pre- and
      posttest by clinical rates and the spatiotemporal parameters of self-paced
      walking. The two groups were not significantly different in demographic,
      clinical, and gait data at baseline. There were no significant differences
      between groups for clinical data at posttest. The purposed multimodal exercise
      program has found improvement in some kinematic gait parameters for the TG.
      Further study in the form of randomized controlled trial would be required to
      establish effectiveness of the intervention.

PMID- 22389828
TI  - Serine 129 Phosphorylation of alpha-Synuclein Cross-Links with Tissue
      Transglutaminase to Form Lewy Body-Like Inclusion Bodies.
AB  - Intraneuronal depositions of alpha-synuclein have been implicated in the
      pathogenesis of Parkinsons's disease (PD). Previous reports have identified the
      crosslinking between alpha-synuclein and tTG (tissue transglutaminase) in both PD
      patients and the cellular model. However, no researches have been conducted to
      further investigate their interaction in physiological conditions. To address
      this question, we generated the SH-SY5Y cell line which stably expressed the wild
      type or mutant (Ser129Ala) alpha-synuclein. After the treatment with okadaic
      acid, alpha-synuclein started forming aggregates upon the activation of tTG.
      Coimmunoprecipitation assays revealed a decreased interaction of the mutant alpha
      synuclein S129A with tTG compared with the wild-type alpha-synuclein. Cells
      expressing the wild-type alpha-synuclein showed increased eosinophilic
      cytoplasmic inclusion bodies that resembled Lewy bodies compared with the mutant.
      Double immunofluorescence staining confirmed the colocalization of the
      phosphorylated alpha-synuclein and the tTG in the cells. The S129A mutant
      demonstrated a lesser degree of colocalization than the wild type.

PMID- 22389829
TI  - Targeting fatigue in stroke patients.
AB  - Symptoms of fatigue are often reported by patients in both the acute and chronic
      stages of recovery following a stroke. It is commonly associated with low mood
      and sleep disturbances, but can arise in their absence. However, it has also been
      associated with poorer long-term outcome and, as such, its aetiology warrants a
      greater understanding. There is convincing evidence that inflammatory cascades
      and cytokine signalling precipitated by the infarct promote fatigue, and these
      pathways may harbour therapeutic targets in its management.

PMID- 22389830
TI  - A comprehensive study of repetitive transcranial magnetic stimulation in
      Parkinson's disease.
AB  - The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for
      Parkinson's disease (PD) remain controversial. We performed a comprehensive study
      to examine whether rTMS is a safe and effective treatment for PD. Twelve PD
      patients received rTMS once a week. The crossover study design consisted of 4
      week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease
      Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL
      Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale,
      Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and
      cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects.
      Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS
      scores significantly, while the sham rTMS did not. There were no significant
      changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems
      to be a safe and effective therapeutic option for PD patients, especially in a
      wearing-off state.

PMID- 22389831
TI  - Transient oculomotor palsy after influenza vaccination: short report.
AB  - Several neurological complications have been described after influenza
      vaccination. Oculomotor palsy has not been yet related with influenza vaccine. We
      report a 79-year-old man who developed an acute transient right oculomotor palsy
      two days after a routine influenza vaccination, for which no other cause was
      identified. There was no evidence of diabetes, glucose intolerance, high blood
      pressure, hipercholesterolemia, smoking, obesity, systemic vasculitis, or other
      risk factor for ischemic neuropathy. The cerebrospinal fluid was normal as well
      as the MRI and MRA scans. The differential diagnosis and the possible
      relationship between the vaccine and the oculomotor palsy are discussed.

PMID- 22389832
TI  - Focal epilepsy associated with glioneuronal tumors.
AB  - Glioneuronal tumors are an increasingly recognized cause of partial seizures that
      occur primarily in children and young adults. Focal epilepsy associated with
      glioneuronal tumors is often resistant to pharmacological treatment. The cellular
      mechanisms underlying the epileptogenicity of glioneuronal tumors remain largely
      unknown. The involved mechanisms are certain to be multifactorial and depend on
      specific tumor histology, integrity of the blood-brain barrier, characteristics
      of the peritumoral environment, circuit abnormalities, or cellular and molecular
      defects. Glioneuronal tumors presenting with epilepsy were observed to have
      relatively benign biological behavior. The completeness of the tumor resection is
      of paramount importance in avoiding tumor progression and malignant
      transformation, which are rare in cases of epileptogenic glioneuronal tumors. An
      evolving understanding of the various mechanisms of tumor-related
      epileptogenicity may also lead to a more defined surgical objective and effective
      therapeutic strategies, including antiepileptogenic treatments, to prevent
      epilepsy in at-risk patients.

PMID- 22389833
TI  - Optic nerve and spinal cord are the major lesions in each relapse of Japanese
      multiple sclerosis.
AB  - For the purpose of predicting multiple sclerosis (MS) and neuromyelitis optica
      (NMO) relapses in Japanese population, we evaluated the localization and age of
      each demyelinating attack. We retrospectively analyzed the 78 medical records of
      Japanese MS and NMO patients. Then we identified 49 cases of relapsing-remitting
      type patients and defined each of 116 demyelinating attacks. NMO had an older age
      at onset than MS, although the initial symptoms cannot predict the clinical
      phenotypes. Only 21.3% of demyelinating attacks were localized in the cerebrum
      and 78.7% were optic-spinal lesions, although MS comprised 70% and NMO comprised
      30% of these 78 cases. Brainstem lesion had a relative male predominancy and a
      young age at attack. Our findings showed that optic nerve and spinal cord lesions
      are the major and critical lesions in each attack of Japanese CNS demyelinating
      diseases. There might be distinctive Japanese pathogenic features even in Western
      type MS.

PMID- 22389834
TI  - Ca/Calmodulin and presynaptic short-term plasticity.
AB  - Synaptic efficacy is remodeled by neuronal firing activity at the presynaptic
      terminal. Presynaptic activity-dependent changes in transmitter release induce
      postsynaptic plasticity, including morphological change in spine, gene
      transcription, and protein synthesis and trafficking. The presynaptic transmitter
      release is triggered and regulated by Ca(2+), which enters through voltage-gated
      Ca(2+) (Ca(V)) channels and diffuses into the presynaptic terminal accompanying
      action potential firings. Residual Ca(2+) is sensed by Ca(2+)-binding proteins,
      among other potential actions, it mediates time- and space-dependent synaptic
      facilitation and depression via effects on Ca(V)2 channel gating and vesicle
      replenishment in the readily releasable pool (RRP). Calmodulin, a Ca(2+)-sensor
      protein with an EF-hand motif that binds Ca(2+), interacts with Ca(V)2 channels
      and autoreceptors in modulation of SNARE-mediated exocytosis.

PMID- 22389835
TI  - Initial Stroke Severity Is the Major Outcome Predictor for Patients Who Do Not
      Receive Intravenous Thrombolysis due to Mild or Rapidly Improving Symptoms.
AB  - Intravenous tissue plasminogen activator thrombolysis for stroke is still under
      use. A substantial proportion of excluded patients for mild or improving symptoms
      are dependent at discharge. We prospectively recruited 49 patients who did not
      receive thrombolysis because of mild or improving symptoms. 32 had favorable
      outcome (mRS <= 2) and 17 had unfavorable outcome (mRS > 2) at discharge.
      Comparisons were made between the two groups. Age was older (72.5 +/- 10.0 versus
      64.7 +/- 13.2 years, P = 0.037), and initial National Institutes of Health Stroke
      Scale (NIHSS) score (5.7 +/- 4.0 versus 2.2 +/- 2.1, P < 0.001) was higher in the
      unfavorable group. Diastolic blood pressure was higher in the favorable group (98
      +/- 15 versus 86 +/- 18  mmHg; P = 0.018). Atrial fibrillation (3.1 versus 23.5%;
      P = 0.043) and ipsilateral artery stenosis (21.9 versus 58.8%; P = 0.012) were
      more frequently found in the unfavorable group. Percentage of patients excluded
      from thrombolysis due to improving symptoms was higher in the unfavorable group
      (40.6 versus 82.4%; P = 0.005). Initial NIHSS score, but not other factors, was
      identified by logistic regression analysis as a major independent predictor for
      unfavorable outcome (OR 1.44; 95%CI, 1.03-2.02).

PMID- 22389836
TI  - Physical activity in the prevention and treatment of stroke.
AB  - The role of physical activity in the prevention of stroke is of great interest
      due to the high mortality and significant impact of stroke-related morbidity on
      the individual and on healthcare resources. The use of physical activity as a
      therapeutic strategy to maximise functional recovery in the rehabilitation of
      stroke survivors has a growing evidence base. This narrative review examines the
      existing literature surrounding the use of exercise and physical therapy in the
      primary and secondary prevention of stroke. It explores the effect of gender,
      exercise intensities and the duration of observed benefit. It details the most
      recent evidence for physical activity in improving functional outcome in stroke
      patients. The review summaries the current guidelines and recommendations for
      exercise therapy and highlights areas in which further research and investigation
      would be useful to determine optimal exercise prescription for effective
      prevention and rehabilitation in stroke.

PMID- 22389837
TI  - Translation, Cross-Cultural Adaptation, and Validation of the Parkinson's Disease
      Quality of Life Questionnaire (PDQL), the "PDQL-BR", into Brazilian Portuguese.
AB  - Translate, culturally adapt, and validate the "Parkinson's Disease Quality of
      Life" (PDQL) BR, into Brazilian Portuguese. Fifty-two patients answered the PDQL
      BR. Twenty-one patients answered the PDQL-BR again 14 days later. The UPDRS and
      HY scale was applied. Validation was evaluated using psychometric properties,
      checking the quality of the data, reliability, and validity. Quality of the data
      was evaluated based on occurrence of ceiling and floor effects. Reliability was
      evaluated based on: internal consistency of an item, homogeneity, and
      reproducibility. Validation was checked through the evaluation of convergent and
      discriminatory validation. There was no ceiling and floor effect. When evaluating
      reliability, items 20, 30, and 37 showed correlation of 0.34, 0.26, and 0.37,
      respectively, to your scale; the other items was higher than 0.4. The alpha
      Cronbach coefficient was higher than 0.7 for most domains. There was good
      reproducibility. There were no meaningful changes in the PDQL-BR translation and
      cross-cultural adaptation.

PMID- 22389838
TI  - Short-Term and Two-Year Rate of Recurrent Cerebrovascular Events in Patients with
      Acute Cerebral Ischemia of Undetermined Aetiology, with and without a Patent
      Foramen Ovale.
AB  - Purpose. We investigated stroke recurrence in patients with acute ischemic stroke
      of undetermined aetiology, with or without a patent foramen ovale (PFO). Methods.
      Consecutive stroke patients underwent to Transcranial Doppler and Transesophageal
      Echocardiography for PFO detection. Secondary stroke prevention was based on
      current guidelines. Results. PFO was detected in 57/129 (44%) patients. The rate
      of recurrent stroke did not significantly differ between patients with and
      without a PFO: 0.0% versus 1.4% (1 week), 1.7% versus 2.7% (1 month), and 3.5%
      versus 4.2% (3 months), respectively. The 2-year rates were 10.4% (5/48) in
      medically treated PFO and 8.3% (6/72) in PFO-negative patients (P = 0.65), with a
      relative risk of 1.25. No recurrent events occurred in 9 patients treated with
      percutaneous closure of PFO. Conclusion. PFO was not associated with increased
      rate of recurrent stroke. Age-related factors associated with stroke recurrence
      in cryptogenic stroke should be taken into account when patients older than 55
      years are included in PFO studies.

PMID- 22389839
TI  - Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and
      Pediatric Glioblastomas.
AB  - While allelic losses and mutations of tumor suppressor genes implicated in the
      etiology of astrocytoma have been widely assessed, the role of epigenetics is
      still a matter of study. We analyzed the frequency of promoter hypermethylation
      by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT,
      RASSF1A, p14(ARF), and p16(INK4A)), in astrocytoma samples and cell lines.
      RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma
      samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN
      showed a slight methylation signal in only one GBM and one pilocytic astrocytoma,
      and in two cell lines; while p14(ARF) and p16(INK4A) did not show any evidence of
      methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again
      the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no
      alterations. Lack or reduced expression of RASSF1A in cell lines was correlated
      with the presence of methylation. RASSF1A promoter hypermethylation might be used
      as a diagnostic marker for secondary GBM and pediatric GBM. Promoter
      hypermethylation might not be an important inactivation mechanism in other genes
      like PTEN, p14(ARF) and p16(INK4A), in which other alterations (mutations,
      homozygous deletions) are prevalent.

PMID- 22389840
TI  - Computed three-dimensional atlas of subthalamic nucleus and its adjacent
      structures for deep brain stimulation in Parkinson's disease.
AB  - Background. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is one
      of the standard surgical treatments for advanced Parkinson's disease. However, it
      has been difficult to accurately localize the stimulated contact area of the
      electrode in the subthalamic nucleus and its adjacent structures using a two
      dimensional atlas. The goal of this study is to verify the real and detailed
      localization of stimulated contact of the DBS electrode therapeutically inserted
      into the STN and its adjacent structures using a novel computed three-dimensional
      atlas built by a personal computer. Method. A three-dimensional atlas of the STN
      and its adjacent structures (3D-Subthalamus atlas) was elaborated on the basis of
      sagittal slices from the Schaltenbrand and Wahren stereotactic atlas on a
      personal computer utilizing a commercial software. The electrode inserted into
      the STN and its adjacent structures was superimposed on our 3D-Subthalamus atlas
      based on intraoperative third ventriculography in 11 cases. Findings. Accurate
      localization of the DBS electrode was identified using the 3D-Subthalamus atlas,
      and its clinical efficacy of the electrode stimulation was investigated in all 11
      cases. Conclusion. This study demonstrates that the 3D-Subthalamus atlas is a
      useful tool for understanding the morphology of deep brain structures and for the
      precise anatomical position findings of the stimulated contact of a DBS
      electrode. The clinical analysis using the 3D atlas supports the contention that
      the stimulation of structures adjacent to the STN, particularly the zona incerta
      or the field of Forel H, is as effective as the stimulation of the STN itself for
      the treatment of advanced Parkinson's disease.

PMID- 22389841
TI  - Relationship between Latitude and Melanoma in Italy.
AB  - Objective. Evaluate the ecological relationship between skin melanoma
      epidemiology and latitude in Italy. Methods. We used data from the Italian
      network of cancer registries (Airtum). In a Poisson model, we evaluated the
      effect on incidence, mortality, and survival of latitude, adjusting for some
      demographic, social, phenotypic, and behavioural variables. Results. Incidence
      increased in Italy by 17% for each degree of increase in latitude. The effect of
      latitude was statistically significantly present also adjusting for other
      variables (incidence rate ratio = 1.08). The effect of latitude on increasing
      mortality (mortality rate ratio = 1.27) and improving survival (relative excess
      risk of death = 0.93) was no longer present in the multivariate model.
      Conclusion. Melanoma incidence, mortality, and survival vary in Italy according
      to latitude. After adjustment for several confounders, incidence still grows with
      growing latitude. Presumably, latitude expresses other variables that might be
      related to individual susceptibility and/or local care.

PMID- 22389842
TI  - Synthesis and Inhibiting Activity of Some 4-Hydroxycoumarin Derivatives on HIV-1
      Protease.
AB  - Six novel 4-hydroxycoumarin derivatives were rationally synthesized, verified,
      and characterized by molecular docking using crystal HIV-1 protease. Molecular
      docking studies predicted antiprotease activity of (7) and (10). The most
      significant functional groups, responsible for the interaction with HIV-1
      protease by hydrogen bonds formation are pyran oxygen, atom, lactone carbonyl
      oxygen and one of the hydroxyl groups. The newly synthesized compounds were
      biologically tested in MT-4 cells for inhibiting HIV-1 replication, exploring the
      protection of cells from the cytopathic effect of HIV measured by cell survival
      in MTT test. One derivative -7 showed 76-78% inhibition of virus infectivity with
      IC(50) = 0.01 nM, much less than the maximal nontoxic concentration (1 mM).
      Antiprotease activity of 7 in two different concentrations was detected to be
      25%. Nevertheless, the results of study of (7) encourage using it as a
      pharmacophore for further synthesis and evaluation of anti-HIV activity.

PMID- 22389843
TI  - Synthesis, characterization, and antibacterial studies of mixed ligand
      dioxouranium complexes with 8-hydroxyquinoline and some amino acids.
AB  - Mixed ligand complexes of dioxouranium (VI) of the type [UO(2)(Q)(L).2H(2)O] have
      been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and amino
      acids (HL) such as L-threonine, L-tryptophan, and L-isoleucine as secondary
      ligands. The metal complexes have been characterized by elemental analysis,
      electrical conductance, magnetic susceptibility measurements, and spectral and
      thermal studies. The electrical conductance studies of the complexes indicate
      their nonelectrolytic nature. Magnetic susceptibility measurements revealed
      diamagnetic nature of the complexes. Electronic absorption spectra of the
      complexes show intraligand and charge transfer transitions, respectively. Bonding
      of the metal ion through N- and O-donor atoms of the ligands is revealed by IR
      studies, and the chemical environment of the protons is confirmed by NMR studies.
      The thermal analysis data of the complexes indicate the presence of coordinated
      water molecules. The agar cup and tube dilution methods have been used to study
      the antibacterial activity of the complexes against the pathogenic bacteria S.
      aureus, C. diphtheriae, S. typhi, and E. coli.

PMID- 22389844
TI  - Molecular-field-based three-dimensional similarity studies on quinoline-based CNS
      active agents.
AB  - A series of quinoline-based agents with CNS activity have been analyzed for their
      three-dimensional similarity with respect to a set of standard atypical
      antipsychotics. The method aligns the molecules based on their molecular fields
      represented as local extrema of electrostatic, van der Waals, and hydrophobic
      potentials of the molecule termed "field points." The compounds in the series
      were found to demonstrate relatively lesser 3D similarity to the dibenzodiazepine
      derivative clozapine. Similarity values were higher with respect to extended
      chain compounds ketanserin, ziprasidone, and risperidone. The results obtained
      were found to agree with the physicochemical similarity of the compounds reported
      earlier.

PMID- 22389845
TI  - Formulation and evaluation of controlled-release tablet of zolpidem tartrate by
      melt granulation technique.
AB  - The present investigation describes the influence of the concentration of PEG
      6000 as a melt binder and ratio of HPMC K4M : PVP on Zolpidem tartrate controlled
      release tablet formulations using 3(2) full factorial design. The ratio of HPMC
      K4M and PVP K30 (X(1)) and the concentration of melt binder (X(2)) were selected
      as independent variables, and drug release at 1 hr (Q(1)), 4 hr (Q(4)), 8 hr
      (Q(8)), diffusion coefficient (n), and release rate constant (K) were selected as
      a dependent variable. Tablets were prepared by melt granulation technique and
      evaluated for various evaluation parameters. It was observed that concentration
      of melt binder had significant effect on Q(1), Q(4), n, and K Binder
      concentration 25% w/w was found optimum. Optimized formulation (F(7)) showed good
      similarity with theoretical profile of drug. The X(2) variable had a significant
      effect on dependent variables, and the X(1) variable had no significant effect on
      dependent variables.

PMID- 22389846
TI  - Preparation of Fluconazole beta-Cyclodextrin Complex Ocuserts: In Vitro  and  In
      Vivo Evaluation.
AB  - The main purpose of the present study was to develop ocuserts of Fluconazole beta
      CD (beta-cyclodextrin) complex and to evaluate both in vitro and in vivo.
      Fluconazole was made complex with beta-CD, and the release rate was controlled by
      HPMC K(4)M and ethyl cellulose polymers using dibutyl Phthalate as permeability
      enhancer. Drug-polymer interactions were studied by Fourier transform infrared
      spectroscopic studies. The formulated ocuserts were tested for physicochemical
      parameters of in vitro release and in vivo permeation in rabbits. The optimized
      formulations (F-5 and F-8) were subjected to stability studies. The formulated
      ocuserts were found to have good physical characters, thickness, diameter,
      uniformity in weight, folding endurance, less moisture absorption, and controlled
      release of drug both in vitro and in vivo. The optimized formulations retained
      their characteristics even after stability studies. The study clearly showed that
      this technique was an effective way of formulating ocuserts for retaining the
      drug concentration at the intended site of action for a sufficient period of time
      and to elicit the desired pharmacological response.

PMID- 22389847
TI  - Preparation and characterisation of highly loaded fluorescent chitosan
      nanoparticles.
AB  - Chitosan (CS) nanoparticles have been developed as a versatile drug delivery
      system to transport drugs, genes, proteins, and peptides into target sites.
      Demands on fluorescent nanoparticles have increased recently due to various
      applications in medical and stem-cell-based researches. In this study,
      fluorescent CS nanoparticles were prepared by a mild method, namely, complex
      coacervation. Entrapment efficiency of sulforhodamine (SR101) loaded into CS
      nanoparticles was investigated to evaluate their capacity in incorporating
      fluorescent molecule. Particle size of produced fluorescent nanoparticles was in
      the range of 600-700 nm, and their particle size was highly dependent on the CS
      molecular weight as well as concentration. A high entrapment efficiency of SR101
      into CS nanoparticles could also be obtained when it was dissolved in methanol.
      In conclusion, highly loaded fluorescent CS nanoparticles could be easily
      prepared using complex coacervation method and therefore can be applied in
      various medical researches.

PMID- 22389848
TI  - Water-soluble Fraction of Abelmoschus esculentus L Interacts with Glucose and
      Metformin Hydrochloride and Alters Their Absorption Kinetics after
      Coadministration in Rats.
AB  - This study was done to investigate the effects of water-soluble fraction (WSF) of
      the fruits of Abelmoschus esculentus L (okra/lady's fingers) on absorption of
      oral glucose as well as metformin from the gastrointestinal tract in the Long
      Evans rats. WSF of A. esculentus significantly (P < 0.05) reduced the absorption
      of glucose as studied in the 24 hrs fasting rats. The effect of WSF of A.
      esculentus on metformin absorption was studied in alloxan-induced diabetic rats.
      Significant differences (P < 0.05) were observed in the average blood glucose
      level from 2 to 24 hours after metformin therapy in presence (33.6 to 34.2
      mmol/L) or absence (15.2 to 20.2 mmol/L) of oral WSF of A. esculentus. In both of
      the experiments, Na-carboxymethylcellulose (CMC) was used as positive control.
      The results of this study indicate that A. esculentus may improve glycemic
      control but should not be taken concurrently with metformin hydrochloride in
      controlling diabetes mellitus.

PMID- 22389849
TI  - Formulation and evaluation of floating oral in situ gelling system of
      amoxicillin.
AB  - Purpose. Effective Helicobacter pylori eradication requires delivery of the
      antibiotic locally in the stomach. High dose of amoxicillin (750 to 1000 mg) is
      difficult to incorporate in floating tablets but can easily be given in liquid
      dosage form. Keeping the above facts in mind, we made an attempt to develop a new
      floating in situ gelling system of amoxicillin with increased residence time
      using sodium alginate as gelling polymer to eradicate H. pylori. Methods.
      Floating in situ gelling formulations were prepared using sodium alginate,
      calcium chloride, sodium citrate, hydroxypropyl methyl cellulose K100, and sodium
      bicarbonate. The prepared formulations were evaluated for solution viscosity,
      floating lag time, total floating time, and in vitro drug release. The
      formulation was optimized using a 3(2) full factorial design. Dissolution data
      were fitted to various models to ascertain kinetic of drug release. Regression
      analysis and analysis of variance were performed for dependent variables.
      Results. All formulations (F(1)-F(9)) showed floating within 30 s and had total
      floating time of more than 24 h. All the formulations showed good pourability. It
      was observed that concentration of sodium alginate and HPMC K100 had significant
      influence on floating lag time, cumulative percentage drug release in 6 h and 10
      h. The batch F(8) was considered optimum since it showed more similarity in drug
      release (f(2) = 74.38) to the theoretical release profile. Conclusion. Floating
      in situ gelling system of amoxicillin can be formulated using sodium alginate as
      a gelling polymer to sustain the drug release for 10 to 12 h with zero-order
      release kinetics.

PMID- 22389850
TI  - Morphology and release kinetics of protein-loaded porous poly(l-lactic Acid)
      spheres prepared by freeze-drying technique.
AB  - Freeze-drying a biodegradable polymer, poly(L-lactic acid) (PLLA), from 1,4
      dioxane solutions provided very porous spherical particles of ca. 3 mm in radius
      with specific surface area of 8-13 m(2) g(-1). The surface of the particle was
      found to be less porous compared with its interior. To apply the freeze-dried
      PLLA (FDPLLA) to drug delivery system, its morphology and drug releasing kinetics
      were investigated, bovine serum albumin (BSA) being used as a model drug
      compound. Immersion of FDPLLA into a BSA aqueous solution gave BSA-loaded FDPLLA,
      where mass fraction of the adsorbed BSA reached up to 79%. Time-dependent release
      profile of BSA in water suggested a two-step mechanism: (1) very rapid release of
      BSA deposited on and near the particle surface, which results in an initial
      burst, and (2) leaching of BSA from the interior of the particle by the diffusion
      process. It was suggested that the latter process is largely governed by the
      surface porosity. The porosity of both the interior and surface was found to
      decrease remarkably as the concentration of the original PLLA/1,4-dioxane
      solution increases, C(0). Thus, C(0) is a key parameter that controls the loading
      and releasing of BSA.

PMID- 22389851
TI  - Separation and quantification of eight antidiabetic drugs on a high-performance
      liquid chromatography: its application to human plasma assay.
AB  - An analytical method based on isocratic reverse phase high-performance liquid
      chromatography was developed and validated for the separation and quantification
      of eight antidiabetic drugs: rosiglitazone, pioglitazone, glipizide, gliclazide,
      repaglinide, nateglinide, glibenclamide, and glimepiride for their application in
      human plasma assay. Metformin is used as internal standard. Analysis was done on
      Onyx monolithic C(18) column (100 * 4.6 mm, i.d., 5 MUm) using a mixture of 0.05%
      formic acid in water and methanol in the ratio of 42 : 58 (v/v) fixed at a flow
      rate of 0.5 mL/min, and they were monitored at 234 nm. Separation was achieved in
      less than 20 min. The calibration curves were linear in the range of 50-2000
      ng/mL. The method was validated for its recovery, intra- and interday precision,
      stability, specificity, and selectivity. Plasma samples were prepared using solid
      phase extraction of analytes. Hence, the developed method was found to be
      suitable for the routine analysis of selected antidiabetic drugs in biological
      matrices.

PMID- 22389852
TI  - Labeling of tannic Acid with technetium-99m for diagnosis of stomach ulcer.
AB  - Tannic acid is a polyphenolic compound that could be labeled with technetium-99m.
      To produce about 90% yield of  (99m)Tc-tannic acid in acidic media (pH), the
      conditions required were 150 MUg tin chloride, 30 min reaction time, and 200 MUg
      of the substrate. (99m)Tc-tannic was stable for 6 h. Oral biodistribution of
      (99m)Tc-tannic showed that it concentrated in the stomach ulcer to reach about
      50% of the total injected dose at 1 h after orall administration. This
      concentration of (99m)Tc-tannic in stomach ulcer may be sufficient to radio-image
      the presence of ulcer in the stomach.

PMID- 22389853
TI  - Pharmacokinetic Compatibility Study of Lidocaine with EXPAREL in Yucatan
      Miniature Pigs.
AB  - We explored the potential for EXPAREL to interact with lidocaine. Sixty (60) male
      Yucatan Swine were randomized into 20 groups (N = 3/group). EXPAREL (2 or 4
      mg/kg) and/or lidocaine HCl solution 1% or 2% (with epinephrine 1 : 200,000) were
      injected subcutaneously along a 5 cm virtual incision line. The effects on the
      pharmacokinetics of bupivacaine and lidocaine were examined when 5, 10, 20, and
      40 minutes had passed between administration of lidocaine and EXPAREL. Systemic
      exposure to lidocaine was increased (AUC(0-24 hr) by 48%; C(max) by 1,640%) when
      lidocaine (4 mg/kg) was followed 5 minutes later by EXPAREL (4 mg/kg) compared to
      lidocaine administered alone. Plasma bupivacaine was increased (AUC(0-24 hr) by
      50-95%; C(max) by 67-1,000%) when lidocaine (4 mg/kg) was followed 5 or 10
      minutes later by EXPAREL (4 mg/kg) compared to EXPAREL alone. While EXPAREL
      should not be admixed with lidocaine, this study shows that local administration
      of EXPAREL after at least 20 minutes following local administration of lidocaine
      did not increase the release of either drug.

PMID- 22389854
TI  - Preparation of carboxymethylchitosan nanoparticles with Acid-sensitive bond based
      on solid dispersion of 10-hydroxycamptothecin.
AB  - Solid dispersions were prepared by a conventional solvent evaporation method from
      the water-insoluble model drug 10-hydroxycamptothecin (HCPT) and
      monomethoxypoly(ethylene glycol) 2000 (mPEG 2000). And then one type of novel
      biodegradable nanoparticles, the solid dispersion (HCPT/mPEG-CHO) grafted with
      carboxymethylchitosan (HCPT/mPEG-g-CMCTS) was synthesized. The increase in HCPT
      solubility of solid dispersion was up to 21-fold compared with the original drug.
      With the increasing of the amount of mPEG-CHO, solubility of HCPT was from 7.71
      MUg/mL to 25.82 MUg/mL. Colloid systems based on solid dispersion were stable in
      aqueous medium at 5 degrees C. After 5 months storage at 25 degrees C, the solid
      dispersions do not change at all. HCPT/mPEG-g-CMCTS was synthesized by grafting
      reaction of carboxymethylchitosan with mPEG-CHO to form Schiff base which is
      sensitive to acid environment. The release rate of HCPT from this conjugate in pH
      5.4 was much higher than that in the environment of pH 7.4 and p H 4.5. The
      cumulative release percentages are 45%, 25%, and 15%, respectively. The
      cumulative release percentage of HCPT in conjugate was only 15% within 85 h while
      the original drug was up to 70% in pH 7.4, showing a significant slow-release
      property. This drug model can be attractive candidates as delivery biosystems in
      tumor therapy.

PMID- 22389855
TI  - Formulation and optimization of sustained release Stavudine microspheres using
      response surface methodology.
AB  - The aim of the current study was to formulate and optimize the formulation on the
      basis of in vitro performance of microsphere. A 3(2) full factorial design was
      employed to study the effect of independent variables, polymer-to-drug ratio
      (X(1)) and stirring speed (X(2)), on dependent variables, encapsulation
      efficiency, particle size, and time to 80% drug release. The best batch exhibited
      a high entrapment efficiency of 70% and mean particle size 290 MUm. The drug
      release was also sustained for more than 12 hours. The study helped in finding
      the optimum formulation with excellent sustained drug release.

PMID- 22389856
TI  - Formulation and evaluation of transdermal patch of repaglinide.
AB  - Repaglinide has the half life of 1 hour, and bioavailability in the body is 56%
      due to first-pass metabolism. The total daily dose of Repaglinide is 16 mg (e.g.,
      4 mg four times daily depending on meal patterns); hence, it required frequent
      dosing. Transdermal patch of Repaglinide was prepared to sustain the release and
      improve bioavailability of drug and patient compliance. Different formulations
      were prepared by varying the grades of HPMC and concentration of PVP K30 by
      solvent casting method. The prepared formulations were evaluated for various
      parameters like thickness, tensile strength, folding endurance, % elongation, %
      moisture content, % moisture uptake, % drug content, in vitro drug release, in
      vitro permeation, and drug excipient compatibility. A 3(2) full factorial design
      was applied to check the effect of varying the grades of HPMC (X(1)) and PVP
      concentration (X(2)) on the responses, that is, tensile strength, percentage drug
      released in 1 hr (Q(1)), 9 hr (Q(9)), and diffusion coefficient as a dependent
      variables. In vitro release data were fitted to various models to ascertain
      kinetic of drug release. Regression analysis and analysis of variance were
      performed for dependent variables. The results of the F2 statistics between
      factorial design batches and theoretical profile were used to select optimized
      batch. Batch F6 was considered optimum batch which contained HPMC K100 and PVP
      (1.5%), showed release 92.343% up to 12 hr, and was more similar to the
      theoretical predicted dissolution profile (f(2) = 69.187).

PMID- 22389857
TI  - Enhancement or Suppression of ACE Inhibitory Activity by a Mixture of Tea and
      Foods for Specified Health Uses (FOSHU) That Are Marketed as "Support for Normal
      Blood Pressure".
AB  - The ACE inhibitory activities of mixtures of FOSHUs (Healthya, Goma-Mugicha,
      Lapis Support and Ameal) were examined in order to identify any antihypertensive
      interactions. Among combinations of Healthya with other samples that contain
      active peptides, only that with Ameal was found to have no inhibitory activity.
      Enhanced activity was observed in 2 other mixtures. The activity of a mixture of
      tea polyphenols and the whey component extracted from an Ameal solution was
      significantly decreased, thus demonstrating that whey protein lowered the ACE
      inhibitory activity of Healthya. Although oral administration of tea polyphenols
      alone significantly decreased SBP in SHR at 2 and 4 hr, combined administration
      with Ameal failed to decrease SBP at the same time points. In conclusion, the
      simultaneous intake of tea and FOSHUs that contain active peptides might affect
      daily self-antihypertensive management via enhancement or suppression of ACE
      inhibitory activity.

PMID- 22389858
TI  - Development and evaluation of microemulsions for transdermal delivery of insulin.
AB  - Insulin-loaded microemulsions for transdermal delivery were developed using
      isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant,
      and isopropyl alcohol as the cosurfactant. The pseudoternary phase diagrams were
      constructed to determine the composition of microemulsions. The insulin
      permeation flux of microemulsions containing oleic acid as oil phase through
      excised mouse skin and goat skin was comparatively greater than that of
      microemulsions containing isopropyl myristate as oil phase. The insulin-loaded
      microemulsion containing 10% oleic acid, 38% aqueous phase, and 50% surfactant
      phase with 2% dimethyl sulfoxide (DMSO) as permeation enhancer showed maximum
      permeation flux (4.93 +/- 0.12 MUg/cm(2)/hour) through goat skin. The in vitro
      insulin permeation from these microemulsions was found to follow the Korsmeyer
      Peppas model (R(2) = 0.923 to 0.973) over a period of 24 hours with non-Fickian,
      "anomalous" mechanism. Together these preliminary data indicate the promise of
      microemulsions for transdermal delivery of insulin.

PMID- 22389859
TI  - Pharmacogenetics and gender association with psychotic episodes on nortriptyline
      lower doses: patient cases.
AB  - The variation in individual responses to psychotropic drug treatment remains a
      critical problem in the management of psychotic disorders. Although most patients
      will experience remission, some patients may develop drug-induced adverse effects
      that may range from troublesome to life threatening. Antidepressants are freely
      prescribed by general practitioners, and there should be constant awareness in
      the medical community about possible serious side effects. We describe two cases
      of adverse drug reactions on low dosage treatment that led to extreme psychotic
      episodes as examples of the potential for dangerous side effects. The patients
      developed adverse reactions on the normal recommended dosage of nortriptyline, a
      tricyclics antidepressant (TCA). Both were females, with no history of
      antidepressant treatment, unsocial behaviour, nor any family history of
      psychosis, but both experienced severe psychiatric symptoms. Pharmacogenetic
      tests can easily be performed and interpreted according to the likelihood of
      adverse reactions and should be included in toxicity interpretation.

PMID- 22389861
TI  - Solubility and dissolution enhancement of etoricoxib by solid dispersion
      technique using sugar carriers.
AB  - The aim of the present study was to improve solubility and dissolution of the
      poorly aqueous soluble drug, etoricoxib by solvent evaporation technique using
      various sugar carriers, such as lactose, sucrose, and mannitol. Etoricoxib solid
      dispersions and their respective physical mixtures using lactose, sucrose, and
      mannitol were prepared in different ratios by solvent evaporation technique. The
      percent yield, drug content, saturation solubility, and in vitro dissolution of
      etoricoxib solid dispersions and physical mixtures were analyzed. Etoricoxib
      solid dispersions were characterized by FTIR spectroscopy, XRD, and DSC analysis.
      The FTIR spectroscopic analysis revealed the possibility of intermolecular
      hydrogen bonding in various solid dispersions. The XRD and DSC studies indicated
      the transformation of crystalline etoricoxib (in pure drug) to amorphous
      etoricoxib (in solid dispersions) by the solid dispersion technology. Both the
      aqueous solubility and dissolution of etoricoxib were observed in all etoricoxib
      solid dispersions as compared with pure etoricoxib and their physical mixtures.
      The in vitro dissolution studies exhibited improved dissolution in case of solid
      dispersion using lactose than the solid dispersions using both sucrose and
      mannitol. The in vitro dissolution of etoricoxib from these solid dispersions
      followed Hixson-Crowell model.

PMID- 22389860
TI  - Human tissue in the evaluation of safety and efficacy of new medicines: a viable
      alternative to animal models?
AB  - The pharma Industry's ability to develop safe and effective new drugs to market
      is in serious decline. Arguably, a major contributor to this is the Industry's
      extensive reliance on nonhuman biology-based test methods to determine potential
      safety and efficacy, objective analysis of which reveals poor predictive value.
      An obvious alternative approach is to use human-based tests, but only if they are
      available, practical, and effective. While in vivo (phase 0 microdosing with high
      sensitivity mass spectroscopy) and in silico (using established human biological
      data), technologies are increasingly being used, in vitro human approaches are
      more rarely employed. However, not only are increasingly sophisticated in vitro
      test methods now available or under development, but the basic ethically approved
      infrastructure through which human cells and tissues may be acquired is
      established. Along with clinical microdosing and in silico approaches, more
      effective access to and use of human cells and tissues in vitro provide exciting
      and potentially more effective opportunities for the assessment of safety and
      efficacy of new medicines.

PMID- 22389862
TI  - Study on HIF-1alpha Gene Translation in Psoriatic Epidermis with the Topical
      Treatment of Capsaicin Ointment.
AB  - Objective. To investigate the mechanism of capsaicin in treating active psoriasis
      vulgaris. Methods. HIF-1alpha gene translation in active psoriatic lesions before
      and after 21-day treatment with capsaicin ointment was detected by in situ
      hybridization. Results. There was positive staining of HIF-1alpha gene in all the
      layers of psoriatic epidermis (100.0%) before the treatment with capsaicin
      ointment, but the dyeing in epidermis were reduced obviously (22.2%) after the
      treatment for 21 days. Conclusion. HIF-1alpha gene translation in psoriatic
      epidermis was downregulated after capsaicin treatment for 21 days.

PMID- 22389863
TI  - Improving the isotretinoin photostability by incorporating in microemulsion
      matrix.
AB  - The present paper demonstrates the increased photostability of isotretinoin when
      loaded in microemulsion. The photodegradation of isotretinoin, in methanol and
      microemulsion formulation was studied under direct sun light. The
      photodegradation process was monitored by UV spectrophotometry. In methanol
      solution, isotretinoin undergoes complete photodegradation just within a few
      minutes of light exposure. Isotretinoin incorporated in microemulsion formulation
      showed an increased stability in comparison to the methanol solutions. In
      particular for isotretinoin, a residual concentration of 75% was still present
      after a light irradiance versus a residual value of just 16% measured at the same
      time in methanol solution. Further, degradation kinetic parameters of
      isotretinoin-loaded microemulsion formulation were demonstrated increase
      isotretinoin half-life about five-times in comparison with a methanol solution
      under a direct sun light.

PMID- 22389864
TI  - Two new cytotoxic candidaspongiolides from an indonesian sponge.
AB  - Marine sponges have been recognized as potentially rich sources of various
      bioactive molecules. In our continuing search for new secondary metabolites from
      Indonesian marine invertebrates, we collected a sponge, whose extract showed
      cytotoxicity against cultured cells at 0.1 MUg/mL. Purification of the extract
      yielded two new macrolides 2 and 3 along with known candidaspongiolide (1). The
      structures for compounds 2 and 3 were elucidated by spectral analysis ((1)H,
      (13)C, COSY, HMQC, HMBC) and by comparison of their NMR data with those of 1.
      Compounds 2 and 3 exhibited a little more potent cytotoxicity (IC(50) 4.7 and 19
      ng/mL) than that (IC(50) 37 ng/mL) of candidaspongiolide (1) against NBT-T2
      cells.

PMID- 22389865
TI  - Ex vivo evaluation of insulin nanoparticles using chitosan and arabic gum.
AB  - Polymeric delivery systems based on nanoparticles have emerged as a promising
      approach for peroral insulin delivery. The aim of the present study was to
      investigate the release of insulin nanoparticulate systems and ex vivo studies.
      The nanoparticles were prepared by the ion gelation method. Particle size
      distribution, zeta potential, and polydispersity index of the nanoparticles were
      determined. It was found that the nanoparticles carried positive charges and
      showed a size distribution in the range of 170-200 nm. The electrostatic
      interactions between the positively charged group of chitosan and negatively
      charged groups of Arabic gum play an important role in the association efficiency
      of insulin in nanoparticles. In vitro insulin release studies showed an initial
      burst followed by a slow release of insulin. The mucoadhesion of the nanosystem
      was evaluated using excised rat jejunum. Ex vivo studies have shown a significant
      increase in absorption of insulin in the presence of chitosan nanoparticles in
      comparison with free insulin.

PMID- 22389866
TI  - Development and Validation of a HPLC and an UV Spectrophotometric Methods for
      Determination of Dexibuprofen in Pharmaceutical Preparations.
AB  - A high-performance liquid chromatographic (HPLC) and a ultraviolet (UV) methods
      were developed and validated for the quantitative determination of Dexibuprofen
      (DI) in pharmaceutical dosage form. HPLC was carried out by reversed phase
      technique on a RP-18 column with a mobile phase composed of acetonitrile and 0.5%
      triethylamine (pH 7.5 adjusted with orthophosphoric acid (30 : 70, v/v)). UV
      method was performed with the lambda max at 222.0 nm. Both the methods showed
      good linearity, reproducibility and precision. No spectral or chromatographic
      interferences from the tablet excipients were found in UV and HPLC. The method
      was successfully applied to commercial DEXIFEN tablets. Validation parameters
      such as linearity, precision, accuracy, and specificity were determined. The
      proposed method could be applicable for routine analysis of DI and monitoring of
      the quality of marketed drugs.

PMID- 22389867
TI  - Randomized, double-blind, and placebo-controlled trial of clenbuterol in
      denervated muscle atrophy.
AB  - Objectives. beta(2)-adrenergic agonists, such as clenbuterol, have been shown to
      promote the hypertrophy of healthy skeletal muscles and to ameliorate muscle
      wasting in a few pathological conditions in both animals and humans. We intended
      to investigate the clinical efficacy of clenbuterol on attenuating denervation
      induced muscle atrophy. Methods. A double-blind, placebo-controlled, parallel,
      and randomized trial was employed. 71 patients, suffering from brachial plexus
      injuries, were given either clenbuterol (60 MUg, bid) or placebo for 3 months.
      Before and at the end of the study, patients were given physical examinations,
      biopsies of biceps brachii, electromyograms (EMGs), and other laboratory tests.
      Results. Compared with placebo treatment, clenbuterol significantly mitigated the
      decreases in cross-sectional areas of type I and II muscle fibers and alleviated
      the reduction in fibrillation potential amplitudes, without any adverse effects.
      Conclusions. Clenbuterol safely ameliorated denervated muscle atrophy in this
      cohort; thus larger clinical studies are encouraged for this or other beta(2)
      agonists on denervation-induced muscle atrophy.

PMID- 22389868
TI  - The reliability of the vail sport testTM as a measure of physical performance
      following anterior cruciate ligament reconstruction.
AB  - PURPOSE/BACKGROUND: The decision to return an athlete to sports following
      anterior cruciate ligament reconstruction can be controversial. The purposes of
      this study are 1) to describe a functional test (Vail Sport TestTM) that includes
      the evaluation of muscle strength, endurance, power, and movement quality in
      those patients attempting to return to sports following ACL reconstruction and 2)
      to assess the reliability of the Vail Sport TestTM. METHODS: A prospective cohort
      study design. A total of 30 (12 F, 18 M) subjects (18.1+/-5.3 yrs) volunteered
      for the study. All subjects were post-operative ACL reconstruction (5.2+/-1.9
      months) and were in the process of returning to sports. Each subject completed
      the Vail Sport TestTM and was videotaped from the anterior and lateral view. The
      videotape was then viewed and graded at two different points in time (48 hours
      apart) by three licensed physical therapists. Intraclass correlations (ICCs) were
      calculated to determine intra- and inter-rater reliability. RESULTS: Intra-rater
      reliability was excellent with a range of .95 to 1.0. Reliability values between
      graders were .97 (ICC(2),k) and 1.55 (SEM). CONCLUSIONS: The results of this
      study suggest that the Vail Sport TestTM has excellent reliability when the same
      graders scored the test using video on repeated occasions. In addition, the test
      was reliable between different graders. LEVEL OF EVIDENCE: Level 2b.

PMID- 22389869
TI  - Training errors and running related injuries: a systematic review.
AB  - PURPOSE: The purpose of this systematic review was to examine the link between
      training characteristics (volume, duration, frequency, and intensity) and running
      related injuries. METHODS: A systematic search was performed in PubMed, Web of
      Science, Embase, and SportDiscus. Studies were included if they examined novice,
      recreational, or elite runners between the ages of 18 and 65. Exposure variables
      were training characteristics defined as volume, distance or mileage, time or
      duration, frequency, intensity, speed or pace, or similar terms. The outcome of
      interest was Running Related Injuries (RRI) in general or specific RRI in the
      lower extremity or lower back. Methodological quality was evaluated using quality
      assessment tools of 11 to 16 items. RESULTS: After examining 4561 titles and
      abstracts, 63 articles were identified as potentially relevant. Finally, nine
      retrospective cohort studies, 13 prospective cohort studies, six case-control
      studies, and three randomized controlled trials were included. The mean quality
      score was 44.1%. Conflicting results were reported on the relationships between
      volume, duration, intensity, and frequency and RRI. CONCLUSION: It was not
      possible to identify which training errors were related to running related
      injuries. Still, well supported data on which training errors relate to or cause
      running related injuries is highly important for determining proper prevention
      strategies. If methodological limitations in measuring training variables can be
      resolved, more work can be conducted to define training and the interactions
      between different training variables, create several hypotheses, test the
      hypotheses in a large scale prospective study, and explore cause and effect
      relationships in randomized controlled trials. LEVEL OF EVIDENCE: 2a.

PMID- 22389870
TI  - Molecular characterization of neuroendocrine prostate cancer and identification
      of new drug targets.
AB  - Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer
      that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using
      Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30
      PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a
      large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We
      discovered significant overexpression and gene amplification of AURKA and MYCN in
      40% of NEPC and 5% of PCA, respectively, and evidence that that they cooperate to
      induce a neuroendocrine phenotype in prostate cells. There was dramatic and
      enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase
      inhibitor therapy both in vitro and in vivo, with complete suppression of
      neuroendocrine marker expression following treatment. We propose that alterations
      in Aurora kinase A and N-myc are involved in the development of NEPC, and future
      clinical trials will help determine from the efficacy of Aurora kinase inhibitor
      therapy. SIGNIFICANCE: We report on the largest in-depth molecular analysis of
      NEPC and provide new insight into molecular events involved in the progression of
      prostate cancer.

PMID- 22389871
TI  - Cell-selective inhibition of NF-kappaB signaling improves therapeutic index in a
      melanoma chemotherapy model.
AB  - The transcription factor NF-kappaB promotes survival of cancer cells exposed to
      doxorubicin and other chemotherapeutic agents. IkappaB kinase is essential for
      chemotherapy-induced NF-kappaB activation and considered a prime target for
      anticancer treatment. An IkappaB kinase inhibitor sensitized human melanoma
      xenografts in mice to killing by doxorubicin, yet also exacerbated treatment
      toxicity in the host animals. Using mouse models that simulate cell-selective
      targeting, we found that impaired NF-kappaB activation in melanoma and host
      myeloid cells accounts for the therapeutic and the adverse effects, respectively.
      Ablation of tumor-intrinsic NF-kappaB activity resulted in apoptosis-driven tumor
      regression following doxorubicin treatment. By contrast, chemotherapy in mice
      with myeloid-specific loss of NF-kappaB activation led to a massive intratumoral
      recruitment of interleukin-1beta-producing neutrophils and necrotic tumor
      lesions, a condition associated with increased host mortality but not accompanied
      by tumor regression. Therefore, a molecular target-based therapy may be steered
      toward different clinical outcomes depending on the drug's cell-specific effects.
      SIGNIFICANCE: Our findings show that the IkappaB kinase-NF-kappaB signaling
      pathway is important for both promoting treatment resistance and preventing host
      toxicity in cancer chemotherapy; however, the two functions are exerted by
      distinct cell type-specific mechanisms and can therefore be selectively targeted
      to achieve an improved therapeutic outcome.

PMID- 22389872
TI  - Durable complete response of metastatic gastric cancer with anti-Met therapy
      followed by resistance at recurrence.
AB  - A 48 year-old female with chemo-refractory metastatic gastric cancer to the liver
      was treated on a Phase I clinical trial with MetMAb, a monoclonal antibody
      targeting the Met tyrosine kinase receptor. The primary tumor had high MET gene
      polysomy and evidence for an autocrine production of HGF, the growth factor
      ligand of Met. A complete response was obtained lasting two years; the cancer
      recurred as a peritoneal deposit invading into the transverse colon and a
      gastrohepatic ligament node. Compassionate use of MetMAb therapy at recurrence
      achieved a mixed response--a partial response of the two initial lesions, but
      with development of multiple new foci of carcinomatosis. Tissue and serum studies
      evaluating the Met signaling pathway did correlate with MetMAb treatment response
      initially and at the time of recurrence. SIGNIFICANCE: This research brief is the
      first to describe a durable complete response obtained with a molecularly
      targeted monoclonal antibody, MetMAb, to the receptor tyrosine kinase, Met, in a
      patient with chemorefractory metastatic gastric cancer. It is also the first to
      report biomarkers that predicted therapeutic response to Met inhibition.

PMID- 22389873
TI  - Monitoring foods and nutrients sold and consumed in the United States: dynamics
      and challenges.

PMID- 22389874
TI  - Acculturation and sociocultural influences on dietary intake and health status
      among Puerto Rican adults in Massachusetts.
AB  - BACKGROUND: Previous studies have shown negative consequences of acculturation on
      lifestyle factors, health status, and dietary intake of Hispanic immigrants in
      the US. Despite prevalent type 2 diabetes and low socioeconomic status (SES)
      among Puerto Rican adults living on the US mainland, little is known about
      acculturation in this group. OBJECTIVE: We investigated associations among
      acculturation, lifestyle characteristics, health status, and carbohydrate
      nutrition in Puerto Rican adults. A secondary objective was to investigate
      possible confounding and/or effect modification on these associations by SES.
      DESIGN: Cross-sectional data from the Boston Puerto Rican Health Study, which
      included 1219 Puerto Ricans in the Boston area, aged 45-75 years. STATISTICAL
      ANALYSES: Characteristics were compared using ANCOVA, linear trend and Pearson's
      chi-square tests across quartiles of acculturation. Tests for interaction by
      poverty status were conducted. Proportional contributions of foods to intake of
      total carbohydrate and fiber were assessed using SAS RANK. RESULTS: Levels of
      acculturation were low, despite young age at first arrival to the US mainland
      (25.4 +/- 12.3 y) and long length of stay (34.2 +/- 12.2 y). Greater English
      language use was associated with higher SES, alcohol consumption, physical
      activity, better perceived health, and less central obesity. Acculturation was
      associated with lower legume fiber and greater cereal fiber intake. Among those
      above the poverty threshold, acculturation was associated with lower dietary
      glycemic index and starch intake, and greater fruit and non-starchy vegetable
      intake. CONCLUSIONS: In contrast to studies with Mexican Americans, the
      association of acculturation with dietary quality in these Puerto Rican adults
      was mixed, but tended toward better carbohydrate quality. Dietary recommendations
      should include maintenance of traditional, healthful dietary practices including
      consumption of legumes, but also reduction in refined grains, and greater
      inclusion of fruit, non-starchy vegetables, and whole grains. Interventions to
      improve access to better quality carbohydrate sources are necessary for this
      group disproportionately affected by diabetes.

PMID- 22389875
TI  - Annals of laboratory medicine: quantum leap into the higher quality.

PMID- 22389876
TI  - Current recommendations for laboratory testing and use of bone turnover markers
      in management of osteoporosis.
AB  - Osteoporosis is a major health problem worldwide, and is projected to increase
      exponentially due to the aging of the population. The absolute fracture risk in
      individual subjects is calculated by the use of algorithms which include bone
      mineral density (BMD), age, gender, history of prior fracture and other risk
      factors. This review describes the laboratory investigations into osteoporosis
      which include serum calcium, phosphate, creatinine, alkaline phosphatase and 25
      hydroxyvitamin D and, additionally in men, testosterone. Parathyroid hormone
      (PTH) is measured in patients with abnormal serum calcium to determine its cause.
      Other laboratory investigations such as thyroid function testing, screening for
      multiple myeloma, and screening for Cushing's syndrome, are performed if
      indicated. Measurement of bone turnover markers (BTMs) is currently not included
      in algorithms for fracture risk calculations due to the lack of data. However,
      BTMs may be useful for monitoring osteoporosis treatment. Further studies of the
      reference BTMs serum carboxy terminal telopeptide of collagen type I (s-CTX) and
      serum procollagen type I N-terminal propeptide (s-PINP) in fracture risk
      prediction and in monitoring various treatments for osteoporosis may help
      expedite their inclusion in routine clinical practice.

PMID- 22389877
TI  - Relationship of oxidative stress in hepatitis B infection activity with HBV DNA
      and fibrosis.
AB  - BACKGROUND: The aim of this study was to evaluate oxidative stress in various
      clinical forms of hepatitis B infection and to investigate its role in the
      development of the chronic form of the disease. METHODS: Ninety-three patients
      with inactive hepatitis B surface antigen (HbsAg) carrier state (IHBCS), 65
      patients with chronic hepatitis B infection (CHB), and 42 healthy adults were
      included in the study. The following values were measured and compared in patient
      groups: total antioxidant status (TAS), total oxidative stress (TOS), oxidative
      stress index (OSI), sulfhydryl (SH), lipid peroxidation (LOOH), catalase (CAT),
      and ceruloplasmin. In patients with chronic hepatitis B, these values were
      compared with HBV DNA and fibrosis levels. RESULTS: ALT, TOS, LOOH, and OSI
      levels were higher in the CHB group compared to the other groups (P<0.001).
      Catalase levels increased in the CHB and IHBCS groups compared to the control
      group (P<0.001). Total aminooxidant and ceruloplasmin levels were found to be
      lowest in the CHB group and highest in the control group (P<0.001). Sulfhyrdyl
      was higher in the control group compared to the other groups (P<0.001). In the
      CHB group, there was no correlation between the HBV DNA and OSI (P>0.05).
      CONCLUSIONS: These finding suggested that oxidative stress is associated with
      hepatitis B activity.

PMID- 22389878
TI  - Evaluation of DNA extraction methods and their clinical application for direct
      detection of causative bacteria in continuous ambulatory peritoneal dialysis
      culture fluids from patients with peritonitis by using broad-range PCR.
AB  - BACKGROUND: The aims of this study were to compare several DNA extraction methods
      and 16S rDNA primers and to evaluate the clinical utility of broad-range PCR in
      continuous ambulatory peritoneal dialysis (CAPD) culture fluids. METHODS: Six
      type strains were used as model organisms in dilutions from 10(8) to 10(0) colony
      forming units (CFU)/mL for the evaluation of 5 DNA extraction methods and 5 PCR
      primer pairs. Broad-range PCR was applied to 100 CAPD culture fluids, and the
      results were compared with conventional culture results. RESULTS: There were some
      differences between the various DNA extraction methods and primer sets with
      regard to the detection limits. The InstaGene Matrix (Bio-Rad Laboratories, USA)
      and Exgene Clinic SV kits (GeneAll Biotechnology Co. Ltd, Korea) seem to have
      higher sensitivities than the others. The results of broad-range PCR were
      concordant with the results from culture in 97% of all cases (97/100). Two
      culture-positive cases that were broad-range PCR-negative were identified as
      Candida albicans, and 1 PCR-positive but culture-negative sample was identified
      as Bacillus circulans by sequencing. Two samples among 54 broad-range PCR
      positive products could not be sequenced. CONCLUSIONS: There were differences in
      the analytical sensitivity of various DNA extraction methods and primers for
      broad-range PCR. The broad-range PCR assay can be used to detect bacterial
      pathogens in CAPD culture fluid as a supplement to culture methods.

PMID- 22389879
TI  - Identification of clinical mold isolates by sequence analysis of the internal
      transcribed spacer region, ribosomal large-subunit D1/D2, and beta-tubulin.
AB  - BACKGROUND: The identification of molds in clinical laboratories is largely on
      the basis of phenotypic criteria, the classification of which can be subjective.
      Recently, molecular methods have been introduced for identification of pathogenic
      molds in clinical settings. Here, we employed comparative sequence analysis to
      identify molds. METHODS: A total of 47 clinical mold isolates were used in this
      study, including Aspergillus and Trichophyton. All isolates were identified by
      phenotypic properties, such as growth rate, colony morphology, and reproductive
      structures. PCR and direct sequencing, targeting the internal transcribed spacer
      (ITS) region, the D1/D2 region of the 28S subunit, and the beta-tubulin gene,
      were performed using primers described previously. Comparative sequence analysis
      by using the GenBank database was performed with the basic local alignment search
      tool (BLAST) algorithm. RESULTS: For Aspergillus, 56% and 67% of the isolates
      were identified to the species level by using ITS and beta-tubulin analysis,
      respectively. Only D1/D2 analysis was useful for Trichophyton identification,
      with 100% of isolates being identified to the species level. Performances of ITS
      and D1/D2 analyses were comparable for species-level identification of molds
      other than Aspergillus and Trichophyton. In contrast, the efficacy of beta
      tubulin analysis was limited to genus identification because of the paucity of
      database information for this gene. CONCLUSIONS: The molecular methods employed
      in this study were valuable for mold identification, although the different loci
      used had variable usefulness, according to mold genus. Thus, a tailored approach
      is recommended when selecting amplification targets for molecular identification
      of molds.

PMID- 22389880
TI  - Comparison of sputum and nasopharyngeal swab specimens for molecular diagnosis of
      Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila.
AB  - BACKGROUND: Differentiation of atypical pathogens is important for community
      acquired pneumonia (CAP). In this study, we compared sputum and nasopharyngeal
      swabs (NPS) for use in detection of Mycoplasma pneumoniae (MP), Chlamydophila
      pneumoniae (CP), and Legionella pneumophila (LP), using Seeplex PneumoBacter ACE
      Detection Assay (PneumoBacter; Seegene). METHODS: Sputum and NPS specimens were
      collected from patients in 15 hospitals. DNA was extracted from sputum using
      QIAamp DNA Stool Mini Kit (Qiagen) and from NPS using easyMAG (bioMerieux). Both
      types of specimens were evaluated by multiplex PCR using PneumoBacter. To
      determine the diagnostic performance of this assay, sputum samples were also
      tested using BD ProbeTec ET Atypical Pneumonia Assay (APA; Becton Dickinson).
      RESULTS: Among 217 sputum and NPS, 20 (9.2%), 2 (0.9%), and 0 sputum were
      positive for MP, LP, and CP, respectively, whereas 8 (3.7%) NPS were positive for
      MP. The sputum APA test yielded 186, 206, and 204 interpretable results for MP,
      LP, and CP, respectively. Of these, 21 (11.3%) were positive for MP, 2 (1.0%)
      were positive for LP, and 0 samples were positive for CP. Compared to APA, the
      sensitivity and specificity of the sputum assay for MP were 95.2% and 100.0%,
      respectively, whereas for the NPS assay, these were 38.1% and 93.9%. Sputum
      testing was more sensitive than NPS testing (P=0.002). For LP and CP diagnosis,
      PneumoBacter and APA tests agreed 100%. CONCLUSIONS: Specimen type is crucial and
      sputum is preferred over NPS for simultaneous detection of MP, LP, and CP using
      multiplex PCR in CAP.

PMID- 22389881
TI  - Clinical relevance of pretransplant HLA class II donor-specific antibodies in
      renal transplantation patients with negative T-cell cytotoxicity crossmatches.
AB  - BACKGROUND: We evaluated the clinical relevance of pretransplant donor-specific
      HLA antibodies (DSA) in renal transplantation patients who had negative T-cell
      cytotoxicity crossmatches. METHODS: From 328 consecutive renal transplant
      recipients, we selected 28 patients who had positive pretransplant (historical or
      at the time of transplantation) flow cytometry crossmatches, but negative T-cell
      cytotoxicity crossmatches at the time of transplantation. The presence of DSA and
      its level at the time of transplantation were retrospectively tested using
      Luminex single antigen assays. RESULTS: DSA was present in 16 (57.1%) of 28
      patients. Biopsy-proven acute rejection (9 patients) occurred more frequently in
      patients with DSA than in those without DSA (56.3% vs. 0.0%; P=0.003). The
      positivity rate of class II DSA was significantly higher in patients with
      antibody-mediated rejection (AMR) than in those without AMR (100% vs. 21.7%;
      P=0.003). However, the positivity rate of class I DSA was not different between
      the two groups (40% vs. 40.9%). Among patients with class II DSA, those with AMR
      tended to have higher antibody levels (median fluorescence intensity, MFI) than
      those without AMR (16,359 vs. 5,910; P=0.056). A cut-off MFI value of 4,487 for
      class II DSA predicted the occurrence of AMR with good sensitivity and
      specificity (100% and 87.0%). CONCLUSIONS: In patients with negative T-cell
      cytotoxicity crossmatches, the presence of class II DSA and its level at the time
      of transplantation were associated with the occurrence of AMR. Pretransplant DSA
      measurement with Luminex single antigen assay would be useful in renal
      transplantation.

PMID- 22389882
TI  - Evaluation of recombinant factor VIIa treatment for massive hemorrhage in
      patients with multiple traumas.
AB  - BACKGROUND: Recent studies and case reports have shown that recombinant factor
      VIIa (rFVIIa) treatment is effective for reversing coagulopathy and reducing
      blood transfusion requirements in trauma patients with life-threatening
      hemorrhage. The purpose of this study is to evaluate the effect of rFVIIa
      treatment on clinical outcomes and cost effectiveness in trauma patients.
      METHODS: Between January 2007 and December 2010, we reviewed the medical records
      of patients who were treated with rFVIIa (N=18) or without rFVIIa (N=36) for life
      threatening hemorrhage due to multiple traumas at the Emergency Department of
      Pusan National University Hospital in Busan, Korea. We reviewed patient
      demographics, baseline characteristics, initial vital signs, laboratory test
      results, and number of units transfused, and then analyzed clinical outcomes and
      24-hr and 30-day mortality rates. Thromboembolic events were monitored in all
      patients. Transfusion costs and hospital stay costs were also calculated.
      RESULTS: In the rFVIIa-treated group, laboratory test results and clinical
      outcomes improved, and the 24-hr mortality rate decreased compared to that in the
      untreated group; however, 30-day mortality rate did not differ between the
      groups. Thromboembolic events did not occur in both groups. Transfusion and
      hospital stay costs in the rFVIIa-treated group were cost effective; however,
      total treatment costs, including the cost of rFVIIa, were not cost effective.
      CONCLUSIONS: In our study, rFVIIa treatment was shown to be helpful as a
      supplementary drug to improve clinical outcomes and reduce the 24-hr mortality
      rate, transfusion and hospital stay costs, and transfusion requirements in trauma
      patients with life-threatening hemorrhage.

PMID- 22389883
TI  - Novel mutations in CEBPA in Korean Patients with acute myeloid leukemia with a
      normal karyotype.
AB  - Mutations in the transcription factor CCAAT/enhancer binding protein alpha gene
      (CEBPA) are found in 5-14% of the patients with AML and have been associated with
      a favorable clinical outcome. In this study, we aimed to assess the frequencies
      and characteristics of mutations in CEBPA. Between 2006 and 2009, CEBPA mutations
      were assessed using archival DNA samples obtained from 30 consecutive adult
      patients diagnosed with AML with a normal karyotype at our institution. CEBPA
      mutations were detected using direct sequencing analyses. These mutations were
      detected and described with reference to GenBank Accession No. NM_004364.3. In
      our series, CEBPA mutations were detected in 4 patients (13.3%). These mutations
      occurred as double mutations in all 4 patients. Among the 8 mutant alleles, 5
      were novel (c.179_180dupCG, c.50_53delGCCA, c.178_182delACGTinsTTT,
      c.243_244insGTCG, and c.923_924insCTC). The frequency of occurrence of CEBPA
      mutations in Korean patients with AML is comparable to that in previous reports.
      Long-term follow-up data from a larger series of patients with comprehensive
      molecular profiling are needed to delineate the prognostic implications.

PMID- 22389884
TI  - A case of rosai-dorfman disease with highly elevated serum ferritin.
AB  - Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman
      disease is a rare disorder characterized by proliferation of distinctive
      histiocytes within lymph node sinuses and lymphatics, sometimes involving
      extranodal sites. However, clinical suspicion is difficult and there is also a
      lack of useful diagnostic markers for this disorder prior to histological
      confirmation. High elevation of serum ferritin is known to be a useful diagnostic
      marker for various hematologic diseases, including hemophagocytic
      lymphohistiocytosis and lymphoma. Here, we report a case of fever of unknown
      origin that presented along with highly elevated serum ferritin (5,780 ng/mL),
      and was finally diagnosed as Rosai-Dorfman disease by lymph node biopsy.

PMID- 22389885
TI  - A case of B-cell lymphoma, unclassifiable, with features intermediate between
      diffuse large B-cell lymphoma and Burkitt lymphoma in a Korean child.
AB  - B-cell lymphoma, unclassifiable, with features intermediate between diffuse large
      B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL), is a
      heterogeneous group with some features resembling DLBCL and others resembling BL.
      Here, we report a case of intermediate DLBCL/BL in a Korean child. A 2-yr-old
      male was admitted for evaluation and management of left hip pain.
      Immunohistochemistry of a biopsy of the femur neck revealed tumor cells positive
      for CD20, CD10, BCL2, BCL6, and Ki67. A bone marrow (BM) aspirate smear revealed
      that 49.3% of all nucleated cells were abnormal lymphoid cells, composed of large
      and medium-sized cells. Immunophenotyping of the neoplastic cells revealed
      positivity for CD19, CD10, CD20, and sIg lambda and negativity for CD34, Tdt, and
      myeloperoxidase (MPO). Cytogenetic and FISH analyses showed a complex karyotype,
      including t(8;14)(q24.1;q32) and IGH-MYC fusion. Intensive chemotherapy was
      initiated, including prednisone, vincristine, L-asparaginase, daunorubicin, and
      central nervous system prophylaxis with intrathecal methotrexate (MTX) and
      cytarabine. One month after the initial diagnosis, BM examination revealed the
      persistent of abnormal lymphoid cells; cerebrospinal fluid cytology, including
      cytospin, showed atypical lymphoid cells. The patient was treated again with
      cyclophosphamide, vincristine, prednisone, adriamycin, MTX, and intrathecal MTX
      and cytarabine. The patient died of sepsis 5 months after the second round of
      chemotherapy.

PMID- 22389888
TI  - Annual AAOS meeting: rock stars, fellowship, and MOC.

PMID- 22389886
TI  - False-positive urine pregnancy test due to leukocyte interference.

PMID- 22389889
TI  - Evaluation of pediatric lower extremity fractures managed with external fixation:
      outcomes in a deployed environment.
AB  - External fixation of pediatric lower extremity fractures is usually reserved for
      severe, open fractures in polytraumatized patients, but it is often the only
      available treatment option for deployed military surgeons. We analyzed the
      outcomes and complications of 17 consecutive pediatric long bone fractures
      treated with external fixation at a Forward Surgical Team facility in an austere
      environment during Operation Enduring Freedom in Afghanistan during a 12-month
      period. Treatment consisted of uniplanar external fixation for 12 femoral shaft
      fractures (11 closed), 4 tibial shaft fractures (all open), and 1 subtrochanteric
      fracture (closed) in 14 males and 3 females with an average age of 7.4 years. All
      17 fractures went on to union with no incidences of refracture. Complications
      included 1 broken pin and 3 pin site infections treated with wound care and oral
      antibiotics. In a deployed environment, external fixation is the treatment method
      of choice for lower extremity fractures by virtue of patient, environment,
      equipment, and mission factors. This case series validates the usage of a simple,
      uniplanar external fixator for a variety of open and closed pediatric long bone
      fractures as evidenced by the successful union rate and low number of
      complications.

PMID- 22389890
TI  - Effectiveness of ultraporous beta-tricalcium phosphate (vitoss) as bone graft
      substitute for cavitary defects in benign and low-grade malignant bone tumors.
AB  - We retrospectively evaluated healing with ultraporous beta-tricalcium phosphate
      (beta-TCP [Vitoss; Orthovida, Malvern, Pennsylvania]) bone graft in patients who
      underwent surgical excision or curettage of benign bone lesions subsequently
      filled with bone void filler. Twentynine patients were treated with curettage and
      ultraporous beta-TCP morsels. Radiologic defect size at initial postoperative
      presentation and subsequent visits (minimum follow-up, 6 months) was evaluated.
      Results suggested that an ultraporous beta-TCP synthetic bone graft is effective
      in managing bone voids. The vast majority of patients who undergo curettage for
      benign bone lesions can expect to have complete or near complete healing of these
      defects within 6 months of their surgical procedure with use of ultraporous beta
      TCP morsels.

PMID- 22389891
TI  - When is a medial epicondyle fracture a medial condyle fracture?

PMID- 22389892
TI  - Use of an absorbable plate in the management of a clavicle fracture in an
      adolescent.
AB  - Management of clavicle fractures continues to evolve. Indications for operative
      management seem to be expanding, particularly in athletic youth. Surgical
      intervention has potential complications, many associated with use of metal
      implants. To my knowledge, this case report is the first to describe use of a
      biodegradable implant. The subcutaneous position of the clavicle makes it ideal
      for fixation with a biodegradable implant in which no second surgery is required
      for implant removal.

PMID- 22389893
TI  - Hip hemiarthroplasty periprosthetic loosening caused by papillary ovarian
      carcinoma metastasis in a 78-year-old woman: a rare presentation and a literature
      review.
AB  - Hip arthroplasty failure secondary to septic or aseptic loosening is common, but
      periprosthetic loosening caused by metastasis of a distant primary lesion is
      unusual and seldom described in the literature. In this report, we present the
      case of a 78-year-old woman with bipolar hemiarthroplasty implant loosening
      secondary to metastatic spread of papillary ovarian carcinoma. We also review the
      literature and describe the factors that could possibly predispose to metastatic
      seeding in patients with hip arthroplasty. In addition, we highlight the
      radiologic features that might help differentiate such loosening from other, more
      common causes at an early stage of presentation.

PMID- 22389894
TI  - Infrapatellar branch of saphenous neurectomy for painful neuroma: a case report.
AB  - We present the case of an 18-year-old woman who was healthy other than a history
      of multiple arthroscopic right knee surgeries culminating in subtotal lateral
      meniscectomy in a valgus knee. The patient was referred to our office for
      evaluation for realignment osteotomy and meniscal transplantation. Her diagnosed
      case of neuroma of the infrapatellar branch of the saphenous nerve was managed
      with neurectomy, which produced prompt and complete resolution of pain.

PMID- 22389895
TI  - Use of mineral oil aids scoliosis correction by decreasing implant friction.
AB  - Adolescent idiopathic scoliosis is commonly corrected through posterior spinal
      fusion and instrumentation using pedicle screws. One difficulty in performing the
      correction with this method is the potential for friction at the interface
      between the rod and each individual point of fixation. The authors have found
      that the application of mineral oil at these points of contact serves to reduce
      friction, reducing the need for undue force and increasing the likelihood of
      effective fixation. The lubrication afforded by the mineral oil is particularly
      helpful when performing scoliosis correction using the classic derotation of the
      rod and direct vertebral rotation.

PMID- 22389896
TI  - IT security: what all orthopedic surgeons must know.

PMID- 22389897
TI  - A complex injury of the distal ulnar physis: a case report and brief review of
      the literature.
AB  - Physeal fractures of the distal forearm are common injuries in children and
      adolescents. However, Salter-Harris type III and type IV fractures of the distal
      ulnar epiphysis are often high-energy injuries that require open reduction for
      restoration of anatomical alignment. These injuries are uncommon and there are
      few descriptions of them in the contemporary literature. Here we report the case
      of a 13-year-old boy with a type IV distal ulna fracture not diagnosed with
      standard radiography. After closed manipulation, an incompletely reduced physis
      was suspected on the basis of fluoroscopic imaging and comparison radiographs of
      the contralateral wrist. Computed tomography showed a large, displaced physeal
      fragment. The patient underwent open reduction and internal fixation. Thorough
      radiographic assessment should be conducted when there is a high suspicion for
      these fracture patterns. Appropriate diagnosis can lead to expedient reduction
      and expectant management of sequelae associated with these injuries.

PMID- 22389898
TI  - We are physicians first, orthopedic surgeons second.

PMID- 22389899
TI  - Pyoderma gangrenosum following patellar tendon repair: a case report and review
      of the literature.
AB  - Postoperative pyoderma gangrenosum (PG) is an unusual and devastating
      complication following surgical procedures. This frequently misdiagnosed entity
      can progress rapidly if not identified and treated appropriately. A heightened
      awareness for the diagnosis of PG, coupled with a multidisciplinary approach to
      the disease, is essential to proper management of this entity. We report on a
      patient who developed postoperative PG following open repair of a patellar tendon
      rupture. The follow-up period was 2 years, and a review of the current literature
      is presented. The diagnosis of PG was confirmed by tissue biopsy, and the
      condition was treated with high-dose prednisone and dapsone, with complete
      resolution of symptoms. PG should be part of the differential diagnosis when
      evaluating patients with postoperative wound complications. Awareness of PG is
      the key to diagnosis and treatment of this potentially devastating complication.

PMID- 22389900
TI  - A multi-disciplinary approach to the management of fungal osteomyelitis: current
      concepts in post-traumatic lower extremity reconstruction: a case report.
AB  - Limb salvage in fungal osteomyelitis of the post-traumatic lower extremity
      represents a difficult clinical problem requiring aggressive management. We
      report lower extremity salvage by radical bony debridement, free tissue transfer,
      distraction osteogenesis with bone-docking, and a novel antifungal regimen in a
      clinical setting of infection with Scedosporium inflatum, historically requiring
      amputation in 100% of cases. We treated Scedosporium inflatum osteomyelitis of
      the tibia and calcaneus with radical debridement of infected bone, free partial
      medial rectus abdominis muscle flap coverage, transport distraction osteogenesis,
      and combination voriconazole/terbinafine chemotherapy, a novel antifungal
      regimen. We achieved successful control of the infection, limb salvage, and an
      excellent functional outcome through aggressive debridement of infected bone and
      soft tissue, elimination of dead space within the bony defect, the robust
      perfusion provided by the free flap, the hypervascular state induced by
      distraction osteogenesis, and the synergism of the novel antifungal regimen.

PMID- 22389901
TI  - Radical resection of a venous malformation in middle finger and immediate
      reconstruction using medial plantar artery perforator flap: a case report.
AB  - Reconstruction of complex defects resulting from radical resection of venous
      malformation occurring in other digits except the thumb is challenging because a
      thin and durable flap is required to achieve optimal reconstruction without
      functional impairment. Here, we describe an alternative reconstruction technique
      in a young patient. A 15-year-old female patient with venous malformation of the
      left 3rd finger was treated by radical excision of the tumor including involved
      skin, distal phalanx, and nail bed followed by reconstruction with free medial
      plantar artery perforator flap and split thickness nail bed graft from the great
      toe. Twenty-nine months after surgery, the reconstructed finger showed a
      acceptable aesthetic result without tumor recurrence and excellent restoration of
      motor function. This method can be considered as an useful alternative option for
      management of the digital venous malformation in other digits except the thumb.
      Indications and technical aspects of this method are discussed in this report.

PMID- 22389902
TI  - Autologus groin lymph node transfer for "sentinel lymph network" reconstruction
      after head-and-neck cancer resection and neck lymph node dissection: a case
      report.
AB  - Local or distant metastatic recurrence after therapy is observed in 20-30% of
      cases of head-and-neck cancer. An unfavorable course may occur after cervical
      lymph node dissection due to loss of immunoprotective lymph nodes in the head-and
      neck region. To overcome this problem, we performed autologous lymph node
      transplantation from the groin after head-and-neck cancer resection and cervical
      lymph node dissection. The patient was a 63-year-old man with squamous cell
      carcinoma in the mesopharyngeal lateral wall. After tumor resection and right
      cervical lymph node dissection, a lymph node-containing superficial circumflex
      iliac artery perforator flap was transplanted from the left groin. Pathological
      examination showed that cancer had invaded the primary tumor tissue stump. Thus,
      radiotherapy (66 Gy) was performed for the residual tumor from days 28 to 84
      after surgery. At 12 months after surgery, no recurrent lesion or has developed.
      The biopsy of flap and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1)
      immunostaining shows creditable lymph network in the flap, compared with normal
      free flap. This case suggests that autologous lymph node transplantation may keep
      watch on cancer recurrence by reconstruction of the lymph node system in the
      resected region, and we suggest that this approach may be very useful in cancer
      therapy.

PMID- 22389903
TI  - New onset sarcoid-like granulomatosis developing during  anti-TNF therapy: an
      under-recognised complication.
AB  - Tumour necrosis factor-alpha (TNF-a) antagonists have advanced the treatment of
      inflammatory arthropathies, and are even considered for use in refractory
      sarcoidosis with some success. Paradoxically, cases of new onset sarcoidosis-like
      diseases are increasingly reported in patients receiving TNF-a antagonists. Here,
      we report three cases of sarcoid-like granulomatosis that developed during
      treatment with TNF-a antagonists. Review of the Biologics clinic data base at
      Westmead, Sydney, Australia identified three patients whom, during anti-TNF
      therapy, developed non-caseating granulomas consistent with sarcoidosis. These
      three cases are described with review of the literature from 2000 to 2009 using
      PubMed. One hundred and sixty-nine patients within our data base were reviewed
      for the period 2003-2009. Sarcoidosis-like granulomas developed in three patients
      within a period of 3 to 36 months of treatment with etanercept and/or adalimumab.
      All cases demonstrated non-infective, non-caseating granulomas on renal or lymph
      node biopsy. Improvement was seen in two cases upon cessation of TNF-a antagonist
      and steroid therapy. Interestingly, clinical deterioration was noted upon re
      challenge with the same TNF-a antagonist in one patient. To date, a total of 37
      cases of sarcoid-like granuloma development after anti-TNF therapy have been
      reported in the literature. Development of sarcoidosis-like granulomatosis in
      patients treated with TNF-a antagonists is a phenomenon previously under
      recognised. All three anti-TNF agents have been observed to cause this
      phenomenon, suggesting a 'class effect' rather than being drug specific.

PMID- 22389904
TI  - Persistent febrile illness with  multisystem organ failure associated  with
      clozapine.

PMID- 22389905
TI  - Peripheral hemophagocytosis in malaria infection.

PMID- 22389906
TI  - A tunable Fano resonance in silver nanoshell with a spherically anisotropic core.
AB  - The influences of the anisotropic permittivity and permeability in inner core on
      the Fano resonance have been investigated in Ag nanoshell by means of Mie
      scattering theory. The decreased inner core radius can enhance the coupling
      between superradiant and subradiant dipole modes and hence a distinct Fano
      profile. With increasing the tangential permittivity or permeability of inner
      core, the Fano resonance shows a redshift and the magnitude of Fano profile
      increases. The variation of Fano resonance with anisotropic permeability of the
      core is much weaker than that induced by anisotropic permittivity. We further
      find that the combined action of the increased tangential permittivity and
      permeability of inner core can induce a significant enhancement of Fano resonance
      in Ag nanoshell.

PMID- 22389907
TI  - Development of an online capillary comprehensive 2D-LC system for the analysis of
      proteome samples.
AB  - In the present contribution, a fully automated capillary comprehensive two
      dimensional LC (LC*LC) method, for proteomic analysis, was developed for the
      first time. The investigated platform was characterized by the coupling of high
      pH RP with low-pH RP separations thus ensuring the generation of high peak
      capacity despite the employment of identical stationary phases. The use of
      capillary columns in both dimensions allowed to reduce mobile-phase consumption
      and enhance sensitivity. Fraction transfer from the first to the second dimension
      was performed by means of two 2-position 6-port nano-switching valves, under stop
      flow conditions. Values as high as 1208 and 955 were obtained for the theoretical
      and practical peak capacity, respectively. The investigated LC*LC system showed
      good retention time repeatibility with RSD values ranging from 0.8 to 6.0% for
      the first dimension and from 1.0 to 3.0% for the second dimension, respectively.
      RSD peak area values below 9.5% were also attained, thus demonstrating the
      precision of the LC*LC method employed.

PMID- 22389908
TI  - Electrically assisted liquid-phase microextraction for determination of beta2
      receptor agonist drugs in wastewater.
AB  - Electromembrane extraction followed by high-performance liquid chromatography
      coupled with ultraviolet detection was validated for the determination and
      quantification of salbutamol (SB) and terbutaline in aqueous samples. A 200-V
      electrical field was applied to extract the analytes from 2.5 mL sample solution
      with pH 3.0, through an organic phase which consisted of 80% 2-nitrophenyl octyl
      ether, 10% di-(2-ethylhexyl) phosphate and 10% tris-(2-ethylhexyl)phosphate as
      supported liquid membrane into an acidic acceptor solution with pH 1.0, located
      inside the lumen of a hollow fiber. To achieve the best extraction conditions,
      the organic membrane composition was optimized separately and other parameters,
      such as extraction time, applied voltage and pH in sample solution and acceptor
      phase were studied using experimental design. Under optimal conditions,
      extraction recoveries of 53 and 43% were obtained for SB and terbutaline,
      respectively, which corresponded to preconcentration factors of 89 for SB and 72
      for terbutaline. The method offers acceptable linearity with correlation
      coefficient higher than 0.9947 and relative standard deviation less than 4.7%.
      Finally, it was applied for analysis of drugs in wastewater samples.

PMID- 22389909
TI  - Two-step stacking by sweeping and micelle to solvent stacking using a long-chain
      cationic ionic liquid surfactant.
AB  - Coupling of long-chain ionic liquid (LCIL)-based sweeping and micelle to solvent
      stacking (MSS) in CZE for anionic compounds was proposed. N-Cetyl-N
      methylpyrrolidinium bromide (C16MPYBr) was used as a novel cationic surfactant.
      The capillary column was conditioned with poly(1-vinyl-3-butylimidazolium)
      bromide, a kind of polymeric ionic liquid, to obtain the anodic electroosmotic
      flow (EOF). There is a micellar solution (MS) zone which is prepared with
      C16MPYBr before the sample zone. The micelles penetrated into the sample zone,
      swept and transported the analytes toward the micelle to solvent boundary (MSSB).
      Meanwhile, a sufficient amount of methanol in the background solution (BGS)
      resulted in the reversal of effective electrophoretic mobility of analytes and
      completed the MSS. Under optimal conditions, good linearity (0.9988-0.9999) was
      obtained for model analytes in a wide linear range with limits of detection
      (LODs) from 0.025 to 0.25 mg/L. The intraday and interday repeatabilities (%RSD,
      n=5, 10) were acceptable in the range from 2.12 to 7.29%. 34 and 25 times
      increases in peak area sensitivity for benzoic acid (BA) and 2-nitrophenol (2-NP)
      and 60 times increase in peak height sensitivity for 4-chlorophenol (4-CP) were
      obtained. The proposed method is applied to analyze two spiked environmental
      water samples obtaining satisfactory recoveries.

PMID- 22389910
TI  - Folding research recruits unconventional help.
AB  - A denatured protein chain can find its well-ordered three-dimensional structure,
      the native state, in under a second, using only the information contained in the
      sequence. For researchers, however, the prediction of structures from sequences
      is a hard problem, so they are now recruiting all the help they can get,
      including idle computers and game consoles, game players, and little hints from
      evolution. Michael Gross reports.

PMID- 22389911
TI  - Paul Mead Doty (1920-2011).

PMID- 22389912
TI  - John A. Endler.

PMID- 22389913
TI  - Australia publishes hospital staphylococcus bacteraemia rates.

PMID- 22389914
TI  - Drug donated for treatment of visceral leishmaniasis.

PMID- 22389915
TI  - [When to start antiretroviral therapy in patients with meningeal tuberculosis
      associated with human immunodeficiency virus?].

PMID- 22389916
TI  - [Extended prophylaxis of venous thromboembolic disease in acute medical patients
      with recent reduced mobility. Randomized controlled trial].

PMID- 22389917
TI  - [Influence of antihypertensive treatment schedule on cardiovascular risk in
      hypertensive patients with type 2 diabetes].

PMID- 22389918
TI  - [Beeing a Doctor. . . and continue practicing at 80 years-old].

PMID- 22389920
TI  - You could be one in a million.  Are you doing everything possible to prevent a
      heart attack or stroke?

PMID- 22389919
TI  - Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an
      inadequate response to at least one tumor necrosis factor inhibitor: results of a
      forty-eight-week randomized, double-blind, placebo-controlled, parallel-group
      phase III trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of ocrelizumab plus methotrexate
      (MTX) or leflunomide (LEF) in patients with active rheumatoid arthritis (RA) and
      an inadequate response to tumor necrosis factor alpha inhibitors. METHODS: This
      was a multicenter randomized, double-blind, placebo-controlled, parallel-group
      study that continued over 48 weeks. Patients receiving stable doses of MTX or LEF
      were randomized to receive 2 infusions of placebo (n = 277), ocrelizumab 200 mg
      (n = 278), or ocrelizumab 500 mg (n = 285) on days 1 and 15 as well as at weeks
      24 and 26. Coprimary end points were the proportion of patients with response
      according to the American College of Rheumatology 20% improvement criteria
      (ACR20) at weeks 24 and 48. Secondary end points included the change from
      baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70
      responses. RESULTS: ACR20 responses were 22.0% in the placebo group, 42.2% in the
      ocrelizumab 200 mg group, and 47.9% in the ocrelizumab 500 mg group at 24 weeks
      and 19.5%, 48.7%, and 50.7%, respectively, at 48 weeks (P < 0.0001 versus placebo
      for each comparison at each time point). At 48 weeks, patients receiving both
      doses of ocrelizumab showed significantly improved ACR50 and ACR70 responses of
      ~3-fold versus placebo. Only those in the ocrelizumab 500 mg group showed
      statistically significant (P = 0.0017) inhibition of joint damage progression
      (mean change in the SHS) relative to placebo (61% inhibition) at 48 weeks.
      Overall adverse events and infections during the 48 weeks of study were
      comparable in all treatment groups. Serious infections were observed more
      frequently in patients taking ocrelizumab (5.1% and 4.3%) than in those taking
      placebo (2.5%). CONCLUSION: Patients in both of the ocrelizumab groups met the
      clinical primary efficacy end points. Inhibition of change in the SHS was
      statistically significant at 48 weeks for those in the ocrelizumab 500 mg group.
      The rate of serious infections in this trial was higher for both ocrelizumab
      doses as compared with placebo.

PMID- 22389922
TI  - Ask the doctor.  I am 77 years old, and my doctor recommended surgery to replace
      my aortic valve.  He said my choice is between a mechanical valve and a pig
      valve.  Which is the preferred option?

PMID- 22389921
TI  - Ask the doctor. After a heart attack six years ago, I went on Lipitor
      (atorvastatin) because my doctor said it was proven to reduce the risk of a
      second heart attack in high-risk people like me. Three years ago, I switched to a
      generic (simvastatin) to save money. Now that Lipitor is going generic, should I
      switch back? And can I be assured that the generic version will be as effective
      as brand-name Lipitor at preventing a second heart attack?

PMID- 22389923
TI  - CDC director explains simple steps to saving lives.

PMID- 22389924
TI  - Daily aspirin prevents dangerous clots. Yet only half the people who should take
      it, do.

PMID- 22389925
TI  - Why blood pressure matters so much.  Symptomatically silent, it's often the first
      step toward a stroke or heart attack.

PMID- 22389927
TI  - Zero exposure is the only safe bet with smoking.  Help is out there for those who
      want to quit.

PMID- 22389926
TI  - Keys to managing your cholesterol.  Diet, exercise, and drugs can lower the bad
      and raise the good.

PMID- 22389928
TI  - Developing healthful eating habits is not so hard.  Fresh fruits and veggies are
      satisfying mainstays.

PMID- 22389929
TI  - Increasing activity can be a walk in the park.  Every little bit helps; fun and
      convenience are key factors.

PMID- 22389930
TI  - Million Hearts' national initiatives help you help yourself.

PMID- 22389932
TI  - An ultrasound device barely bigger than a smartphone.

PMID- 22389931
TI  - Weight loss:  fewer calories in, more calories out.  Eating less is the top
      priority; more exercise is second.

PMID- 22389933
TI  - Signaling the brain to lower blood pressure.

PMID- 22389934
TI  - [Listeria monocytogenes--occurrence in food].

PMID- 22389935
TI  - Zinc for colds? Yes, but don't swallow whole!

PMID- 22389936
TI  - Accountable care organizations: HMOs by another name?

PMID- 22389937
TI  - Multicenter randomized controlled trial of pediatric constraint-induced movement
      therapy: 6-month follow-up.
AB  - OBJECTIVE: Pediatric constraint-induced movement therapy (CIMT) is a promising
      intervention for children with unilateral cerebral palsy (CP). This multisite
      randomized controlled trial (RCT) tested the hypothesis that 6 hr versus 3 hr per
      day for 21 days would produce larger maintenance of gains 6 mo posttreatment.
      METHOD: Three sites recruited 18 children (6 per site) ages 3-6 yr with
      unilateral CP. Children were randomly assigned 3 to 6 hr/day of CIMT for 21 days
      and wore a cast on the unaffected extremity the first 18 days. Occupational
      therapists applied a standardized pediatric CIMT protocol. Evaluators blinded to
      condition administered the ASsisted Hand Assessment and the Quality of Upper
      Extremity Skills Test, and parents completed the Pediatric Motor Activity Log pre
      and posttreatment (1 wk, 1 mo, and 6 mo). RESULTS: Both CIMT dosage groups
      showed significant gains on all five assessments with no significant group
      differences at 6 mo follow-up. Effect sizes (n = 15) comparing preintervention to
      postintervention measures (partial eta2) ranged from .33 to .80. CONCLUSION: The
      first multisite RCT of pediatric CIMT confirmed the maintenance of positive
      effects at 6 mo follow-up across multiple functional performance measures. The
      hypothesis that maintenance of effects would differ for children who received 6
      versus 3 hr/day of CIMT (126 vs. 63 total hr) was not supported.

PMID- 22389938
TI  - Colon cleansing perils: where's the evidence?

PMID- 22389939
TI  - Use of robotics in spinal cord injury: a case report.
AB  - OBJECTIVE: We examined the use of robotics to treat upper-extremity (UE)
      dysfunction in tetraplegic patients with spinal cord injury (SCI). METHOD: a 51
      yr-old man with incomplete SCI participated in an occupational therapy program
      that combined traditional occupational therapy with Reo Go(r), a comprehensive
      therapy platform that includes a robotic guide featuring a telescopic arm to
      enable high repetitions of functionally relevant UE exercises. RESULTS: The
      participant demonstrated measurable improvements in active range of motion,
      muscle strength as measured through manual muscle testing, perceived right UE
      function, and self-care performance as measured by the FIMTM. CONCLUSION: The
      findings from this case are promising and demonstrate the Reo Go's utility in
      combination with traditional occupational therapy. However, more research and
      specific protocols that are easily reproducible with robots such as the Reo Go
      are needed to validate this evolving treatment area.

PMID- 22389940
TI  - Effects of sensory-enhanced yoga on symptoms of combat stress in deployed
      military personnel.
AB  - OBJECTIVE: We examined the effects of sensory-enhanced hatha yoga on symptoms of
      combat stress in deployed military personnel, compared their anxiety and sensory
      processing with that of stateside civilians, and identified any correlations
      between the State-Trait Anxiety Inventory scales and the Adolescent/Adult Sensory
      Profile quadrants. METHOD: Seventy military personnel who were deployed to Iraq
      participated in a randomized controlled trial. Thirty-five received 3 wk (>=9
      sessions) of sensory-enhanced hatha yoga, and 35 did not receive any form of
      yoga. RESULTS: Sensory-enhanced hatha yoga was effective in reducing state and
      trait anxiety, despite normal pretest scores. Treatment participants showed
      significantly greater improvement than control participants on 16 of 18 mental
      health and quality-of-life factors. We found positive correlations between all
      test measures except sensory seeking. Sensory seeking was negatively correlated
      with all measures except low registration, which was insignificant. CONCLUSION:
      The results support using sensory-enhanced hatha yoga for proactive combat stress
      management.

PMID- 22389941
TI  - Rater reliability and rater effects of the Safe Driving Behavior Measure.
AB  - We used Safe Driving Behavior Measure (SDBM) to determine rater reliability and
      rater effects (erratic responses, severity, leniency) in three rater groups: 80
      older drivers (mean age = 73.26, standard deviation = 5.30), 80 family members or
      caregivers (age range = 20-85 yr), and two driving evaluators. Rater agreement
      was significant only between the evaluators and the family members or caregivers.
      Participants rated driving ability without erratic effects. We observed an
      overall rater effect only between the evaluator and family members or caregivers,
      with the evaluators being the more severe rater group. Training family members or
      caregivers to rate driving behaviors more consistently with the evaluator's
      ratings may enhance the SDBM's usability and provide a role for occupational
      therapists to interpret proxy reports as an entry point for logical and efficient
      driving safety interventions.

PMID- 22389942
TI  - How sensory experiences of children with and without autism affect family
      occupations.
AB  - We used a grounded theory approach to data analysis to discover what effect, if
      any, children's sensory experiences have on family occupations. We chose this
      approach because the existing literature does not provide a theory to account for
      the effect of children's sensory experiences on family occupations. Parents of
      six children who were typically developing and six children who had autism were
      interviewed. We analyzed the data using open, axial, and selective coding
      techniques. Children's sensory experiences affect family occupations in three
      ways: (1) what a family chooses to do and not to do; (2) how the family prepares;
      and (3) the extent to which experiences, meaning, and feelings are shared.

PMID- 22389943
TI  - Relationship between intuition and emotional intelligence in occupational
      therapists in mental health practice.
AB  - OBJECTIVE: Clinical reasoning studies have acknowledged tacit aspects of
      practice, and recent research suggests that clinical reasoning contains intuition
      informed by tacit knowledge. Intuition also appears to be influenced by awareness
      and understanding of emotions. This study investigated the relationship between
      intuition and emotional intelligence among occupational therapists in mental
      health practice. METHOD: We mailed a survey containing measures of cognitive
      style and of use of emotional competencies at work and demographic questions to
      400 members of the national occupational therapy association; 134 occupational
      therapists responded. RESULTS: A moderate relationship was found between
      intuitive cognitive style and emotional intelligence. Experienced therapists
      scored higher on the use of emotional competencies at work and reported a
      preference for an intuitive cognitive style to a greater extent than novices.
      CONCLUSION: This study represents the first attempt to explore occupational
      therapists' preferred cognitive style and self-reported emotional intelligence.
      Findings suggest that exploring emotions through reflective practice could
      enhance intuitive aspects of clinical reasoning.

PMID- 22389944
TI  - Interrater reliability in finger joint goniometer measurement in Dupuytren's
      disease.
AB  - We investigated interrater reliability of motion (ROM) measurement in the finger
      joints of people with Dupuytren's disease. Eight raters measured flexion and
      extension of the three finger joints in one affected finger of each of 13 people
      with different levels of severity of Dupuytren's disease, giving 104 measures of
      joints and motions. Reliability measures, represented by intraclass correlation
      coefficient (ICC), standard error of the mean (SEM), and differences between
      raters with the highest and lowest mean scores, were calculated. ICCs ranged from
      .832 to .973 depending on joint and motion. The SEM was <=3 degrees  for all
      joints and motions. Differences in mean between highest and lowest raters were
      larger for flexion than for extension; the largest difference was in the distal
      interphalangeal joint. The results indicate that following these standardized
      guidelines, the interrater reliability of goniometer measurements is high for
      digital ROM in people with Dupuytren's disease.

PMID- 22389945
TI  - Pilot randomized controlled trial investigating cognitive strategy use to improve
      goal performance after stroke.
AB  - OBJECTIVE: The authors compared changes in client performance on three goals
      poststroke after the Cognitive Orientation to daily Occupational Performance (CO
      OP) intervention or standard occupational therapy (SOT) to determine the
      magnitude and direction of change. METHOD: Eight people living in the community
      following a stroke were randomly assigned to receive CO-OP (n = 4) or SOT (n =
      4). CO-OP is a 10-session, cognitive-oriented approach to improving performance
      that uses client-driven cognitive strategies. SOT was therapist driven and
      combined task-specific and component-based training. Goal performance was
      measured by the therapist-rated Performance Quality Rating Scale (PQRS) and the
      participant-rated Canadian Occupational Performance Measure (COPM). RESULTS:
      Using Mann-Whitney U test, we found that CO-OP participants showed significantly
      greater improvement in performance (PQRS, p = .02; COPM Performance, p = .02)
      compared with SOT but no improvement in satisfaction (COPM Satisfaction, p =
      .38). CONCLUSION: The CO-OP group demonstrated larger performance improvements
      than the SOT group. Because of the promising results, an investigation using a
      larger sample is warranted.

PMID- 22389946
TI  - Certified driver rehabilitation specialists' preferred situations for driving
      simulator scenarios.
AB  - The use of driving simulators is increasing in clinical settings that provide
      driving evaluation and rehabilitation. To identify the driving simulator
      scenarios desired by certified driving rehabilitation specialists (CDRSs), we
      developed a questionnaire consisting of 22 driving scenario situations. A total
      of 164 CDRSs rated each situation in terms of its importance for inclusion in
      simulator-based driving. The four situations they identified as most critical
      were turning left across oncoming traffic, navigating four-way intersections with
      traffic lights or signs, driving in multiple lanes with traffic on both sides,
      and reacting to unexpected events that require emergency braking or aggressive
      maneuvers to prevent an accident. We conducted exploratory and confirmatory
      factor analyses to group the 22 driving scenario situations. The model with the
      best fit included 11 situations forming three factors: (1) Intersections, (2)
      Roadway and Traffic Conditions, and (3) Environmental Conditions. Future studies
      should include these factors in driving simulator scenarios and evaluate their
      clinical efficacy in driving evaluation and rehabilitation.

PMID- 22389947
TI  - Is reporting race and ethnicity essential to occupational therapy evidence?

PMID- 22389948
TI  - ["The informed patient": who, if not we?"].

PMID- 22389949
TI  - Findings of research misconduct.

PMID- 22389950
TI  - Relationships among blood leptin and adiponectin levels, fat mass, and bone
      mineral density in Japanese pre- and postmenopausal women.
AB  - We conducted a survey of 111 healthy middle-aged and older women, aged 40 to 80
      years, to elucidate the relationships between blood leptin and adiponectin levels
      and bone mineral density (BMD) in September 2008. We examined the associations
      between the blood levels of these adipocytokines and the lumbar spine (L2-L4),
      left femoral, and distal forearm BMD after adjustment for the age and body fat
      percentage. No correlation was observed between leptin and the BMD. This is
      presumably due to the fact that the influence of menopause, age, duration of
      postmenopausal period, and body fat percentage on the BMD is greater than that of
      leptin levels in healthy women. The adiponectin levels were significantly
      correlated negatively with the lumbar spine and femoral BMD in premenopausal
      women, and with forearm BMD in postmenopausal women, regardless of adjustment for
      age and body fat percentage. It seems likely that adiponectin influences the BMD
      at different skeletal sites in pre- and postmenopausal women.

PMID- 22389951
TI  - New dopamine agonist pramipexole improves parkinsonism and depression in
      Parkinson's disease.
AB  - Previous studies have shown that pramipexole might have the potential to improve
      depressive symptoms in patients with Parkinson's disease. To provide more
      evidence, in five Japanese patients at Hoehn & Yahr stage 1-3 we evaluated the
      Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating
      Scale (HAMD) and Montgomery Asberg Depression Rating Scale (MADRS) at our
      hospital. After the pramipexole treatment, each total score of UPDRS, HAMD and
      MADRS significantly decreased compared with that before the treatment. Our data
      indicate that pramipexole improves depressive symptoms in patients with
      Parkinson's disease.

PMID- 22389952
TI  - Treatment of iliac artery rupture during percutaneous transluminal angioplasty: a
      report of three cases.
AB  - We report three cases of iliac artery rupture during percutaneous transluminal
      angioplasty (PTA). In all three cases, bleeding was temporarily controlled by
      inflating an angioplasty balloon at the site of bleeding. Two patients underwent
      subsequent surgical revascularization, and one underwent endovascular stent
      grafting but ultimately required a surgical bypass. Arterial rupture is a rare
      but potentially fatal complication of PTA. Although stent grafts for peripheral
      arteries are not yet covered by Japanese medical insurance, it is a useful
      treatment for arterial injury during PTA.

PMID- 22389953
TI  - Recanalization after successful occlusion by transcatheter arterial embolization
      with N-butyl cyanoacrylate for traumatic splenic artery injury.
AB  - A 70-year-old male with advanced pancreatic cancer went into shock after
      sustaining a traumatic abdominal injury. Computed tomography (CT) showed a
      hematoma with extravasation around the pancreas and hemorrhagic ascites. After
      direct catheterization failed due to angiospasm, the ruptured splenic artery was
      successfully occluded by transcatheter arterial embolization (TAE) using an N
      butyl cyanoacrylate (NBCA)-lipiodol mixture and the patient recovered from shock
      without complications. A follow-up CT obtained 20 days later showed a recurrent
      splenic artery pseudoaneurysm without extravasation. A repeat angiogram
      demonstrated recanalization of the splenic artery and pseudoaneurysm via
      antegrade. We embolized the recanalized pseudoaneurysm using metallic coils for
      isolation. Our experience indicates that adequate concentration and volume of the
      NBCA-lipiodol mixture should be considered depending on the vascular spasm in a
      patient with hypovolemic shock.

PMID- 22389954
TI  - A first case of hepatic angiosarcoma treated with recombinant interleukin-2.
AB  - A 60 year-old woman was admitted to our hospital because of management of
      multiple liver tumors. According to image findings and liver biopsy, she was
      diagnosed as having epithelioid hemangioendothelioma of the liver accompanied by
      metastases in the spleen, lungs and bones. Based on the spread of the liver
      tumors and the extensive systemic metastases, she was considered inoperable.
      Instead, she received hepatic arterial infusion therapy using recombinant
      interleukin-2. However, she died due to liver failure about two months after
      admission. Autopsy revealed that the liver tumor was angiosarcoma. It is
      difficult to differentiate angiosarcoma from epithelioid hemangioendothelioma
      based on the image findings and pathological findings of percutaneous liver
      biopsy. Many cases are diagnosed as angiosarcoma at autopsy. There is no
      established effective treatment for hepatic angiosarcoma, because the tumor stage
      at the time of diagnosis is often progressive. To date, immunotherapy with
      recombinant interleukin-2 has been reported to be effective clinically for
      cutaneous angiosarcoma, such as of the scalp and facial skin. To our knowledge,
      there have been no reported cases of hepatic angiosarcoma treated with
      recombinant interleukin-2. Our case is important should recombinant interleukin-2
      be considered effective for hepatic angiosarcoma in the future.

PMID- 22389955
TI  - [Risk factors and strategies of dental implants in the maxillary posterior
      without sufficient bone available].
AB  - There are two ways to place dental implants in the maxillary posterior without
      sufficient bone available, one is the maxillary sinus floor bone augmentation
      technique, the other is to evade maxillary sinus. The maxillary sinus floor bone
      augmentation technique may result in a series of complication, and reduce
      obedience of patients for implant surgery. According to principles of the best
      bone utilization, the evaded maxillary sinus implant technique is more simple,
      more economic, more predictable, and more shortage of time, compared with the
      maxillary sinus floor bone augmentation technique, and has certain technological
      advantages in some special cases.

PMID- 22389956
TI  - [The influence of glazing and polishing on ceramic surface roughness and
      bacterial adhesion].
AB  - OBJECTIVE: To compare the influence of polishing and glazing on ceramic surface
      roughness and bacterial adhesion to the resulted surfaces. METHODS: The surface
      of the ceramic plates were tested and analyzed by atomic force microscope. The
      influence of resulted surface on Streptococcus mutans adhesion were also
      evaluated. RESULTS: The ceramic surface became much smoother after polishing with
      diamond paste or self-glazing. A positive correlation between surface roughness
      and bacterial adhesion were observed. Compared with surfaces polished with rubber
      wheel, surfaces polished with diamond paste or self-glazing reduced bacterial
      adhesion to the surface (P<0.05). CONCLUSION: Polishing with diamond paste could
      be an alternative to self-glazing on ceramic surface roughness and bacterial
      adhesion.

PMID- 22389957
TI  - [Culturing and characterization of human periodontal ligament stem cells and
      investigating their chemotactic responses to bone morphogenetic protein-2].
AB  - OBJECTIVE: To investigate the chemotactic response of human periodontal ligament
      stem cells (PDLSCs) to bone morphogenetic protein-2 (BMP-2). METHODS: Human
      PDLSCs were obtained from clinically healthy premolars extracted for orthodontic
      reasons and used to isolate PDLSCs by limited dilution method. The expression of
      Vimentin and stem cell marker STRO-1 on PDLSCs were demonstrated with
      immunocytochemical staining. Differentiation assay was used to detect the
      differentiation potential of PDLSCs. Cloning formation experiment and 5-bromo-2
      deoxyuridine (BrdU) incorporation assay were used to determine the stem cell
      characteristics of PDLSCs. The chemotactic effect of BMP-2 on PDLSCs was detected
      by using a 24-multiwell Transwell cell culture chamber. The number of net
      migrated cells was counted in different microscope fields. RESULTS: Human PDLSCs
      displayed positive staining for Vimentin and expressed the stem cell marker STRO
      1. These cells differentiated into osteoblasts and adipocytes under defined
      culture conditions, possessed high self-renewal potential and formed single-cell
      colonies in vitro. The number of cells migrating at concentrations of 100, 200 ng
      mL(-1) of BMP-2 in Transwell cell culture chamber was significantly higher than
      that of negative control (P<0.01). CONCLUSION: BMP-2 may participate in
      regulating chemotaxis of human PDLSCs.

PMID- 22389958
TI  - [The effect of fluoride on dental alloys in different concentrations of fluoride
      artificial saliva].
AB  - OBJECTIVE: To study the changes in surface morphology of cobalt-chromium alloy,
      pure titanium and high-cobalt chromium molybdenum alloy immersed in artificial
      saliva with different concentrations of fluoride, and to analyze the corrosion
      resistance of these metals. METHODS: The three kinds of metal were polished and
      then were immersed in artificial saliva with different concentrations of fluoride
      (0%, 0.05%, 0.2%). All specimens were immersed for 3 weeks at (37.0 +/- 1.0)
      degrees C. Metal surface roughness before and after immersion were measured and
      analyzed by scanning electron microscope (SEM). RESULTS: Metal surface roughness
      was increased with the concentration of fluoride. The surface roughness of the Co
      Cr group and Ti group had a statistically significant difference between before
      and after immersion at the fluoride concentration of 0.05% (P<0.01), and the
      difference between Co-Cr group and vitallium2000 group, Ti group and
      vitallium2000 group were statistically significant difference (P<0.01). The
      differences of three groups before and after immersion were statistically
      significant at the fluoride concentration of 0.2% (P<0.01), and the difference
      among three groups was statistically significant (P<0.01). CONCLUSION: Patients
      who frequently use fluoride products should not use pure titanium or cobalt
      chromium alloy prosthesis. Patients with these three metal prostheses are not
      advised to use high concentration fluoride products.

PMID- 22389959
TI  - [Study on the mechanism of erythritol effecting on Streptococcus mutans].
AB  - OBJECTIVE: To evaluate the effect of erythritol on cell wall structure of
      Streptococcus mutans (S. mutans) and explore its potential mechanism. METHODS:
      Enzyme activities of lactate dehydrogenase (LDH) in bacterial solution were
      detected under respective condition of sucrose and erythritol. A scanning
      electron microscope (SEM) was used to investigate the change of S. mutans' cell
      wall under the condition of sucrose and erythritol. RESULTS: Enzyme activities of
      LDH in erythritol culture medium were different from that in sucrose, but the
      difference was slight. SEM observation showed the integrity of cell wall was not
      destroyed and no content leaked out. CONCLUSION: It's suggested that erythritol
      has an antibacterial effect on S. mutans through no affecting on the normal
      structure of the cell wall of S. mutans.

PMID- 22389960
TI  - [Expression of receptor activator nuclear factor kappa B ligand and
      osteoprotegerin in peri-implant soft tissue and bone tissue].
AB  - OBJECTIVE: To study mRNA expression of receptor activator nuclear factor kappa B
      ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in peri-implant
      tissue during unloading period. METHODS: An animal model of dental implant was
      established in 6 male Beagle dogs of 1-2 years old. Bone remodeling was tested at
      3, 7, 15, 30, 60 and 90 days since the placement of implants. RANKL and OPG mRNA
      expression were quantified by real-time polymerase chain reaction (PCR). Then
      mandibular bones were taken out and the morphological changes were observed by X
      ray, bone tissue was tested by immunohistochemistry stain. RESULTS: The most
      prominent period of bone remodeling occurred at 7th day after the placement of
      implants. The expression of RANKL and OPG increased in a time-dependent manner in
      both soft and hard tissue. After 7 days they gradually decreased. CONCLUSION:
      RANKL and OPG can express in soft tissue, and the changing tendency is consistent
      with the change of bone remodeling, it indicates that RANKL and OPG play an
      important role in the bone remodeling.

PMID- 22389961
TI  - [Fracture of the separated nickel titanium instruments during ultrasonic removal:
      an experimental study].
AB  - OBJECTIVE: This in vitro study is to evaluate the effect of ultrasonic power
      settings and cooling methods on fracture behavior of the separated nickel
      titanium instruments during ultrasonic removal. METHODS: 40 discarded and 10 new
      nickel titanium instruments were used to establish the separated instrument
      removal model. The discarded instruments were divided into four groups according
      to two ultrasonic power settings(6 or 10) and different cooling methods (using
      water coolant or without using water coolant), and all the new instruments were
      put into the group in which ultrasonic vibration was used at a higher power
      setting (10) without using water coolant. The time required for fracture of the
      separated instruments was recorded. RESULTS: The time was longer with statistical
      significance at a lower power setting compared with that at a higher power
      setting regardless of the use of water coolant. The time was longer with
      statistical significance by the use of water coolant compared with that without
      using coolant regardless of power settings (6 or 10). The time required for
      fracture of the new instruments was longer than that of the discarded instruments
      with statistical significance. CONCLUSION: During ultrasonic removal of separated
      nickel titanium instruments, water coolant could decrease the occurrence of
      fracture. When removing separated nickel titanium instruments with ultrasonic
      vibration, an attempt without coolant shouldn't be made at a higher power
      setting.

PMID- 22389962
TI  - [Natural killer and cytotoxic T lymphocyte-mediated cytotoxicity enhanced by
      genetic overexpression of MHC class I chain-related protein A in oral squamous
      cell carcinoma: an experimental study in vivo].
AB  - OBJECTIVE: To investigate the effect on natural killer (NK) and cytotoxic T
      lymphocyte (CTL)-mediated cytotoxicity by genetic overexpression of MHC class I
      chain-related protein A (MICA) in oral squamous cell carcinoma (OSCC). METHODS:
      The OSCC cells by genetic overexpression of MICA were detected to identify the
      biological features including cell growth curve, cell cycle distribution, plate
      clone forming rate and tumorigenicity in nude mice. The expression of natural
      killer group 2, member D (NKG2D) receptor and the cytotoxicity to target tumor
      cells of NK92 and CTL cells, which co-cultured with the transfected OSCC cells or
      the non-transfected or blank vector-transfected controls, were measured by flow
      cytometry and lactate dehydrogenase (LDH) release assay. RESULTS: There was no
      difference in biological features before and after MICA gene transfection to OSCC
      cells. Flow cytometry and LDH release assay showed that MICA-overexpressed OSCC
      cells enhanced the cytotoxicity to target tumor cells and up-regulated the
      expression of NKG2D on NK92 and CTL (P<0.05). CONCLUSION: MICA may be considered
      as a promising immunotherapy target of OSCC.

PMID- 22389963
TI  - [Positron emission tomography/computed tomography for detecting cervical nodule
      metastases of oral and maxillofacial cancer].
AB  - OBJECTIVE: To evaluate the accuracy of positron emission tomography
      (PET)/computed tomography (CT) for detecting cervical nodule metastases of oral
      and maxillofacial cancer. METHODS: Diagnostic test accuracy studies assessing the
      accuracy of PET/CT in diagnosis of cervical metastases of oral and maxillofacial
      cancer were retrieved from the databases of CBM, Medline (OVID) and EMBASE
      (searched on Dec. 13th, 2010) and manual searching of 19 dental journals in
      Chinese. Two researchers were employed in the articles investigation
      independently and evaluated the quality with quality assessment of diagnostic
      accuracy studies (QUADAS). Meta-analysis was done using MetaDisc 1.4. RESULTS:
      Nine studies met the inclusion criteria and demonstrated high methodological
      quality. The results of Meta-analysis showed that, when nodal level was used as
      unit, PET/CT had good diagnostic value in detecting the cervical nodule
      metastases of oral and maxillofacial cancer. Under such a condition, the pooled
      sensitivity was 0.84, pooled specificity 0.93, pooled diagnostic odds ratio 47.89
      and area under the curve 0.973 8. CONCLUSION: The accuracy of PET/CT for
      detecting cervical nodule metastases of oral and maxillofacial cancer is
      relatively high and it could be used as a good diagnostic tool. And special
      attention should be payed to its diagnostic expense and safety when considering
      PET/CT.

PMID- 22389964
TI  - [Oral health-related quality of life in patients with oral lichen planus].
AB  - OBJECTIVE: To investigate the oral health-related quality of life in patients
      with oral lichen planus (OLP) using the Chinese version of the oral health impact
      profile (OHIP)-14. METHODS: 51 patients with OLP were included and completed the
      questionnaire of OHIP-14 subsequently the REU scoring system was utilized to
      record the local condition and a visual analogue scale (VAS) to rate the pain
      they experienced. The reliability and validity were analyzed by SPSS 16.0
      software. RESULTS: The score of OHIP-14 was 21.67 +/- 9.45, Cronbach's alpha of
      the translated scale was 0.901. The items were divided into 5 domains by factor
      analysis. There was certain logical relation between the items in the same
      domain. There was highly significant association between the OHIP-14 score and
      REU score as well as VAS score (r=0.608, 0.807, P<0.000). CONCLUSION: OHIP-14
      performs well in patients with OLP, and have good validity and reliability.

PMID- 22389965
TI  - [The effects of orthodontic treatment on the morphology of temporomandibular
      joint of the adult with the low angle Class II malocclusions: a CT study].
AB  - OBJECTIVE: To analyze the effects on the morphology of temporomandibular joint
      (TMJ) of the adult with the low angle Class II malocclusions before and after
      orthodontic treatment comparatively. To provide the references for the
      orthodontic treatment of the adults. METHODS: 19 adult patients with low angle
      Class II malocclusions were chosen and treated with Damon self-ligating braces.
      The examinations of 16-slice spiral CT were taken before and after the
      orthodontic treatment. The parameters of skeletal morphology of TMJ were measured
      in the multiplanar reconstruction (MPR) images. The results were analysed
      statistically. RESULTS: The rate of condyles in a center position in the glenoid
      fossa after the treatment was 52.6%(20/38), and the rate of retrodisplacement was
      31.6% (12/38). The position of the condyles before and after the orthodontic
      treatment had significant differences (P<0.05, chi2=4.41, chi2=5.32). The mean
      value of the anterior oblique angle of condyle decreased by 2.32 degrees +/- 1.78
      degrees after treatment, meanwhile the average height of the condylar head
      increased by (1.07 +/- 0.29) mm. There were significant differences in both
      results before and after treatment (P<0.05). CONCLUSION: The orthodontic
      treatment can make the TMJ structures stable and beneficial to relieve the
      symptoms by moving the condyle forward, increasing the height and reconstructing
      the anterior oblique angle of condyle on adult patients with low angle Class II
      malocclusions.

PMID- 22389966
TI  - [Treatment of Class II division 2 malocclusion with herbst appliance in young
      adults].
AB  - OBJECTIVE: To evaluate the effects of angle Class II division 2 malocclusion
      treated with Herbst appliance in young adults. METHODS: Cast splint Herbst
      appliance and multi-bracket appliance were used to treat 12 patients with Class
      II division 2 malocclusion aged from 16 to 25 years old. The lateral cephalograms
      were measured with Winceph 8.0 software and statistical analysis was carried out
      by SPSS 13.0 software. RESULTS: The changes in SNA, Co-Go, Go-Po after treatment
      had no statistical significance (P>0.05). The SNB increased and ANB decreased
      after treatment. Upper and lower incisors labially inclined and inter-incisor
      angle increased. Upper posterior teeth had distal movement, lower posterior teeth
      had mesial movement and extrusion. Mandibular plane angle and occlusal plane
      angle had clockwise rotation. The overbite decreased significantly, and the molar
      relationship changed from Class II to Class I in all patients. CONCLUSION: Herbst
      appliance combined with multi-bracket appliance can be used effectively for
      correcting Class II division 2 malocclusion in young adults.

PMID- 22389967
TI  - [Investigation of nociceptive trigeminal inhibitory tension suppression system
      and occlusal stabilization splint on bruxism patients by using polysomnography].
AB  - OBJECTIVE: To study the short-term effects of nociceptive trigeminal inhibitory
      tension suppression system (NTI-tss) and occlusal stabilization splint (OS) on
      sleep bruxism patients. METHODS: Ten patients received the two splint treatments
      in a randomized cross-over fashion: An NTI-tss and an OS for a 1-week period,
      respectively. Record the bruxism episodes per hour, micro-arousals per hour of
      the patients before wearing the splints (baseline), the first night and 1 week
      after wearing the splints with polysomnography. Statistical analysis was
      performed with SAS 9.1 by means of mixed effect model analysis. RESULTS: There
      were no differences among the micro-arousal index of the baseline, the first
      night and 1 week later with both types of the splints (P>0.05). The NTI-tss was
      associated with a significant reduction in bruxism index compared with baseline.
      The bruxism index of baseline, the first night and 1 week later were 7.50 +/-
      1.11, 3.45 +/- 1.22, and 3.51 +/- 1.03 per hour(the first night vs baseline,
      t=26.52, P<0.01; 1 week vs baseline, t=26.12, P<0.01). There were also
      significant differences in the bruxism index after wearing the OS. The bruxism
      index of baseline, the first night and 1 week later were 7.44 +/- 1.23, 2.97 +/-
      0.91 and 6.43 +/- 1.02 per hour(the first night vs baseline, t=16.79, P<0.01; 1
      week vs baseline, t=3.79, P<0.01). Compared with the NTI-tss group, the reduction
      was much less, especially 1 week later. CONCLUSION: Both the NTI-tss and the OS
      splints can reduce the bruxism index, and have no affect the incidence of micro
      arousal. In this short term study, the NTI-tss was more effective than the OS for
      the treatment of sleep bruxism.

PMID- 22389968
TI  - [Comparative study of root canal morphology of mandibular first premolar by micro
      CT and radio visio graphy].
AB  - OBJECTIVE: To compare the consistency of root canal configuration types of
      mandibular first premolar by using micro-CT and radio visio graphy (RVG).
      METHODS: One hundred extracted mandibular first premolars with complete dental
      root and apex which received no endodontic treatment were randomly selected. Each
      tooth was radiographed with RVG through a buccolingual and mesiodistal direction,
      and then scanned with micro-CT and reconstructed. The classifications of the root
      canal types according to Vertucci's type with the two methods were compared.
      RESULTS: The canal patterns were classified as type I (67%), type III (3%), type
      V (18%), type VII (2%), additional type (10%) with micro-CT and canal patterns as
      type I (71%), type III (2%), type V (23%), type VII (1%), additional type (3%)
      with RVG. 63% of teeth showed one canal in both micro-CT and RVG. Only 25% of
      teeth were diagnosed as complex canal by the same canal type in both micro-CT and
      RVG. The Kappa value between micro-CT and RVG was 0.541 which suggested that the
      two kinds of methods had intermediate consistency. 82.8% of the premolars with
      root groove had two or more than two canals. CONCLUSION: Although RVG can
      basically reflect the root canal system type of the mandibular first premolars in
      vitro, it offers poor accuracy images to complex root canals. Micro-CT three
      dimensional images could clearly and precisely display the root canal system
      morphology of the mandibular first pre-molars in vitro.

PMID- 22389969
TI  - [Analysis of initial endodontic treatment outcome and relevant factors].
AB  - OBJECTIVE: To assess the two-year outcome of initial endodontic treatment and
      evaluate the relationship between the treatment outcome and relevant factors.
      METHODS: A total of 296 patients with 371 teeth received initial endodontic
      treatment between January 2005 and December 2007 were included in the study. The
      teeth were treated using crown down technique, and followed for two years. The
      outcome was examined clinically and radiographically. The relevant factors,
      including pulp vitality, apical periodontitis, the number of tooth root, and
      state of root canal obturation, were analyzed. RESULTS: 143 (176 teeth) from 296
      patients (371 teeth) were followed for two years. 152 teeth (86.36%) with normal
      limits were assessed as "healed" (no apical periodontitis, no signs or symptoms).
      24 teeth were assessed as "disease", 12 teeth were extracted and 12 teeth were
      retreated. The healing rate(HR) was statistically higher for vital teeth (95.38%)
      than that for devital teeth (81.08%). The HR of teeth without apical
      periodontitis (95.24%) was significantly higher than that with apical
      periodontitis (73.24%). Other factors were associated with different HR, but no
      statistical significance (P>0.05). CONCLUSION: Apical periodontitis and pulp
      vitality may be prognostic factors for outcome of initial endodontic treatment.

PMID- 22389970
TI  - [The correlation analysis on Enterococcus faecalis biofilm and clinical
      manifestation in retreatment of root canal].
AB  - OBJECTIVE: To detect the ability of Enterococcus faecalis (E. faecalis) biofilm
      formation and explore the relationship between E. faecalis biofilm formation
      ability and clinical manifestation. METHODS: 96 well plate with the establishment
      of 53 E. faecalis in vitro biofilm model, combined with crystal violet staining,
      was used to test the biofilm formation ability of the clinical isolates E.
      faecalis and analyze the relationship between biofilm formation capacity and
      clinical manifestation. RESULTS: In total 53 E. faecalis strains, 40
      strains(75.47%) had biofilm forming ability. Statistical analysis revealed that
      the capacities of biofilm formation between E. faecalis isolated from with
      fistula and without fistula was significantly different (P<0.05). CONCLUSION: In
      the retreatment of root canal, the ability of biofilm formation of E. faecalis
      separated from the teeth without fistula is better than those separated from the
      teeth with fistula.

PMID- 22389971
TI  - [Diversity research about facial morphology of unilateral complete cleft lip and
      palate affecting by different repair periods of palate repair].
AB  - OBJECTIVE: To evaluate facial morphology characteristics of patients with
      unilateral complete cleft lip and palate (UCCLP) after cleft palate repair in
      different periods. METHODS: 46 nonsyndromic UCCLP patients were chosen as test
      group and divided into three kinds (under 4-year-old, 4-7-year-old, over 7-year
      old) according to periods of palate repair. 38 age and gender matched non-clefts
      children were involved as control group. 26 cephalometric measurements were
      measured to evaluate facial morphology of four groups. RESULTS: Compared with
      patients who received palate repair before 4-year-old, patients who received
      repair after 4-year-old had more protrusive ANS point (Ba-N-ANS, Ba-ANS) and less
      Y-axis angle. Patients who received palate repair after 7-yesr-old had greater A
      PMP and ANS-PMP than patients who received palate repair before 4-year-old,
      patients who received palate repair before 7-year-old had smaller ANS-Me but
      after had no significant difference when compared with non-clefts. CONCLUSION:
      Whenever palate repair is undertaken in the period of maxillary growth and
      development, patients' maxillary growth would be restrained, the delayed repair
      sample have better lower face height, maxillary protrusion, maxillary sagittal
      length and mandible growing direction when compared with the early repair sample,
      that is to say, the delayed repair sample have preferable head-face morphology.

PMID- 22389972
TI  - [Mechanical property of tooth-like yttria-stabilized tetragonal zirconia
      polycrystal by adding rare earth oxide].
AB  - OBJECTIVE: To evaluate the influence of mechanical property of tooth-like yttria
      stabilized tetragonal zirconia polycrystal (Y-TZP) by adding rare earth oxide as
      colorants. METHODS: Six kinds of tooth-like Y-TZP were made by introducing
      internal coloration technology. The colorants included rare earth oxide (Pr6O11,
      CeO2, Er2O3) and transition element oxide (MnO2). Mechanical properties (flexural
      strength, vickers hardness and fracture toughness) were tested. Microstructure
      was examined by scanning electron microscope(SEM), and the fracture model was
      analyzed. RESULTS: The range of flexural strength of the six kinds of tooth-like
      Y-TZP were (792 +/- 20)-(960 +/- 17) MPa, the fracture toughness were (4.72 +/-
      0.31)-(5.64 +/- 0.38) MPam(1/2), and the vickers hardness were (1332 +/- 19)
      (1380 +/- 17) MPa. SEM observation on the cross section of the six kinds of
      sintered composites showed a relatively dense polycrystal structure, and the
      fracture models was mixed type. CONCLUSION: Tooth-like Y-TZP is acquired with
      better mechanical properties (fracture toughness and vickers hardness) by adding
      rare earth oxide as colorants. It is available for clinical application.

PMID- 22389973
TI  - [Effect of lipopolysaccharide and transforming growth factor-beta 1 on expression
      and signal pathway of Toll like receptor 4 in dental pulp cells].
AB  - OBJECTIVE: To explore the expression of Toll like receptor 4 (TLR4) on the pulp
      cells and the change of related signaling molecules under the condition of
      concomitant lipopolysaccharide (LPS) and transforming growth factor-beta 1 (TGF
      beta 1) during the course of pulpitis. METHODS: After treated by LPS and TGF-beta
      1, the expression of TLR4 on pulp cells was detected by flow cytometry (FCM). The
      expressions of signaling molecules evolutionarily conserved signaling
      intermediate in Toll pathways (ECSIT) and nuclear factor-kappaB (NF-kappaB) were
      detected by real-time polymerase chain reaction (real-time PCR) and Western blot.
      The secretion of interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent
      assay (ELISA). Furthermore, the change of corresponding targets in inflamed pulp
      cells from clinical samples were detected by real-time PCR. RESULTS: After
      treated by LPS and TGF-beta 1 in vitro, there was no change in the expression of
      TLR4 on pulp cells, but the secretion of proinflammatory cytokines IL-6
      increased. LPS and TGF-beta 1 could also increase the expression of signal
      downstream ECSIT and actived NF-kappaB. Furthermore, the expression of TLR4 mRNA
      had no increase in inflamed pulp cells from clinical samples, while the
      expression of TGF-beta 1, ECSIT and IL-6 mRNA increased through real-time PCR.
      CONCLUSION: During the course of pulpitis, although the expression of TLR4 on
      pulp cells was inhibited by increased expression of TGF-beta 1, the TLR4 pathway
      was still activated. This effect could be caused through activation of ECSIT
      mediated by LPS, which might inhibit the TGF-beta 1 pathway.

PMID- 22389974
TI  - [Study of labeling human periodontal ligament stem cells with enhanced green
      fluorescent protein by lentivirus vector infection].
AB  - OBJECTIVE: The aim of this study is to optimize conditions for labeling human
      periodontal ligament stem cells (PDLSCs) using enhanced green fluorescent protein
      (eGFP) infected by lentivirus vector and to obtain PDLSCs with high stable
      expressed eGFP. METHODS: PDLSCs were transfected with eGFP by lentivirus vector
      for 48 h via different multiplicity of infection (MOI) (25, 50, 100, 200 and 400)
      and the infection efficiency were analyzed by both fluorescent microscope and
      flow cytometry. The proliferation rate of infected PDLSCs was evaluated by MTT.
      The infected PDLSCs were further for detection of pluripotent, differentiation
      ability and alkaline phosphatase (ALP) expression ability. RESULTS: The infection
      efficiency for each group were 44.7%, 60.9%, 71.7%, 85.8% and 86.9% respectively.
      Proliferation of PDLSCs was not affected when MOI was below 200; however, at MOI
      400, the proliferation ability was affected compared with control group. The
      pluripotent and ALP abilities of PDLSCs were not changed by the infection.
      CONCLUSION: Infection for 48 h at MOI 200 is optimal for labeling PDLSCs with
      eGFP using lentivirus vector, and the proliferation and differentiation abilities
      of PDLSCs are not affected obviously.

PMID- 22389975
TI  - [A study on human tongue cancer cells' proliferation affected by Lactobacillus
      acidophilus].
AB  - OBJECTIVE: To study the effects of Lactobacillus acidophilus (L. acidophilus) on
      the proliferation and cell cycle distribution of human tongue cancer cells
      (Tca8113 cells). METHODS: In vitro cultivated human Tca8113 cells were treated by
      L. acidophilus supernatant, inactivated bacilli, cell free extracts and normal
      culture medium respectively, which were 1, 4, 16-fold(s) dilutelly, to
      investigate the proliferous effects of Tca8113 cells using of inverted
      microscope, cell counting, sulforhodamine B (SRB) and flow cytometry. The free
      radicals and Ca2+ in Tca8113 cells were also studied by confocal laser scanning
      microscope (CLSM). RESULTS: At the 48th hour after adding different L.
      acidophilus components, the Tca8113 cells changed in shape from the diamond-like,
      polygonal and slabs into the elongated form. In the condition of different times
      and different culture concentrations, the proliferation of Tca8113 cells was
      significantly inhibited by L. acidophilus components, which enhanced as the time
      prolonged and the concentrations of each L. acidophilus components increased
      according to the cell counting and the SRB experimental analysis. The cell
      proliferation index (CPI) was significantly reduced (P<0.01). The free radicals
      and Ca2+ in Tca8113 cells under the effect of each L. acidophilus components for
      48 h indicated an obviously rising (P<0.01). CONCLUSION: L. acidophilus restrains
      the proliferation of Tca8113 cells, which might be due to the increase in
      quantity of free radicals and Ca2+ in Tca8113 cells, and might be resulted from
      the release of metabolic products of L. acidophilus.

PMID- 22389976
TI  - [Study on the expression of Toll like receptor 2 and interleukin-1 beta induced
      by Enterococcus faecalis lipoteichoic acid on human periodontal ligament cells].
AB  - OBJECTIVE: To investigate the expression of Toll like receptor 2 (TLR2) and
      interleukin-1 beta (IL-1 beta) of cultured human periodontal ligament cells
      (HPDLCs) activated by Enterococcus faecalis (E. faecalis) lipoteichoic acid
      (LTA). METHODS: HPDLCs that were obtained from the periodontal tissues of healthy
      humans were maintained in proper condition. Flow cytometry was used to detect the
      expression of TLR2 on normal HPDLCs and infectious HPDLCs which were incubated
      with 0.1, 1, 10 microg mL(-1) E. faecalis LTA for 24 h. IL-1 beta was detected by
      enzyme linked immunosorbent assay (ELISA) after incubating with LTA of the above
      concentration for 12, 24 and 48 h or pretreated with TLR2 neutralizing antibody
      for 1 h and then co-cultured with 1 microg mL(-1) LTA for 24 h. RESULTS: E.
      faecalis LTA promoted the expression of TLR2 in normal HPDLCs. The difference had
      statistical significance (P<0.05). IL-1 beta secretion could be detected 12h
      after stimulation with LTA and increasingly escalate within 48h (P<0.05). TLR2
      neutralizing antibody had no evident effect on IL-1 beta generation stimulating
      by E. faecalis LTA. CONCLUSION: E. faecalis LTA can increase the expression of
      TLR2 and IL-1 beta in normal HPDLCs.

PMID- 22389977
TI  - [Association between small ubiquitin-related modifier-1 gene polymorphism and non
      syndromic oral clefting].
AB  - OBJECTIVE: To investigate the association between small ubiquitin-related
      modifier-1 (SUMO-1) gene rs6709162, rs7599810, rs7580433 polymorphism and non
      syndromic oral clefting (NSOC). METHODS: Our study consisted of 208 Ningxia NSOC
      patients, their parents (189 fathers and 176 mothers), 172 nuclear families
      (patients and their parents), and 284 normal controls. DNA was extracted and
      polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP)
      was used to identify rs6709162, rs7599810, rs7580433 genotypes of the samples.
      The data was analyzed by case-control analysis, family based associated test
      (FBAT), and transmission disequilibrium test (TDT). RESULTS: Case-control study
      found that TT genotype's frequency was significantly different in cleft lip and
      cleft palate group compared with the control group at rs7599810 of SUMO-1
      (P=0.01, P=0.01). TDT test showed that rs7599810's T allele had over-transmitted
      (P=0.00) in cleft lip and palate group. FBAT analysis revealed that distribution
      of rs7599810's TT genotype and T allele was significantly different (P=0.00,
      P=0.00). TDT test showed that rs6709162's C allele in cleft palate and cleft lip
      and palate patients had over-transmitted (P=0.00, P=0.01). rs7580433's G allele
      in cleft lip group had over-transmitted (P=0.05). CONCLUSION: SUMO-1 gene
      polymorphism is associated with NSOC.

PMID- 22389978
TI  - [Aphonia induced by block anesthesia of inferior alveolar nerve: a case report].
AB  - Block anesthesia of inferior alveolar nerve is commonly used in oral clinic
      service, but aphonia is rare. A case of aphonia induced by block anesthesia of
      inferior alveolar nerve was reported and the relevant literatures were reviewed.

PMID- 22389979
TI  - [Right submandibular ectopic thymus: a case report].
AB  - Submandibular ectopic thymus is rare in clinical. As this lesion is usually
      asymptomatic, it easily leads to misdiagnosis and treatment failure. This article
      reported a case of submandibular mass caused by ectopic thymus, and discussed
      based on relevant literatures.

PMID- 22389980
TI  - [A multiple three-dimensional interactive teaching mode in teaching diseases of
      oral mucosa].
AB  - Diseases of oral mucosa are characterized by complex etiology, diverse and
      confused clinical manifestations, as well as lack of special therapeutic drugs
      and methods. So it has always been a non-evasive teaching conundrum. This paper
      explored a multiple three-dimensional interactive teaching mode, a combination of
      problem-based learning (PBL), case-based learning (CBL), multimedia, internet and
      evidence-based medicine. It is hoped that its application in the teaching of the
      diseases of oral mucosa will arouse the students' learning interest, broaden
      their professional perspective, cultivate their self-learning ability to find,
      ask, analyze and solve problems, and strengthen their clinical practice capacity.

PMID- 22389981
TI  - Risk factors associated with hospital admission among healthy children with
      adenovirus infection.
AB  - Adenovirus infections mimic bacterial infections on initial presentation in
      healthy children, leading to higher likelihood of hospital admission. The
      objective of this study was to identify risk factors associated with hospital
      admission in previously healthy children with adenovirus infection. This is a
      retrospective study of 125 previously healthy children, who tested positive with
      direct immunofluorescence assay (DFA) for adenoviral infection at our center
      between January 2001 and October 2007. The primary outcome of the study was the
      need for hospital admission. The relationship between clinical variables at
      initial emergency room (ER) presentation and need for hospital admission were
      explored using univariate and multivariate logistic regression models. The
      model's predictive value was investigated by calculating the area under the
      receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test. On
      stepwise multivariate logistic regression analysis, the presence of respiratory
      distress (odds ratio [OR]: 5.6; p = 0.014), acute gastroenteritis (OR: 3.8; p =
      0.019) and wheezes at initial presentation (OR: 6.5; p = 0.003) at the time of
      initial presentation in the ER were associated with need for hospital admission.
      For this model, the area under the ROC curve was 0.79, and there was no evidence
      of lack of fit on Hosmer-Lemeshow goodness-of-fit test (p = 0.56). Our study
      identifies three risk factors, namely, respiratory distress, wheezing and acute
      gastroenteritis, associated with hospital admission for healthy children with
      adenoviral infections.

PMID- 22389982
TI  - Rotavirus epidemiology of children in Bursa, Turkey: a multi-centered hospital
      based descriptive study.
AB  - In this multi-centered study, we aimed to evaluate the distributional incidence
      of rotavirus acute gastroenteritis (RVAGE) according to age groups and
      epidemiological features of hospitalized and outpatient cases in the city center
      of Bursa, Turkey. This study was carried out in a multi-centered setting that
      included the four largest hospitals dealing with more than 90% of the pediatric
      population in Bursa. Children under 15 years old with acute gastroenteritis (AGE)
      were included in the study. During a period of one year, all of the hospitalized
      AGE cases and initially one out of 15 systematically determined outpatien cases
      with AGE were included in the study. RV diagnosis was made by using monoclonal RV
      antigen kits (BioMerieux, France) in fresh stool. Of 542,199 annual general
      hospital visits in those four hospitals, 5,988 were diagnosed with AGE (1.1%).
      The annual general AGE incidence in children under 15 years of age was found to
      be 1.7% per year. The annual incidence of RVAGE was 2.8%, 2.5%, 1.5%, and 0.14%
      in the cases aged < 1 year, < 2 years, < 5 years, and 5-14 years, respectively.
      The hospitalization rate of RVAGE was estimated to be 22.5%, 27%, 20%, and 12.5%
      in the cases aged < 1 year, < 2 years, < 5 years, and 5-14 years, respectively.
      RVAGE comprised 21% of the outpatient AGE cases and 0.35% of the total general
      pediatric outpatient cases. Acute gastroenteritis (AGE)-related hospitalizations
      comprised 5.7% and RVAGE-related hospitalizations 1.6% of all hospitalizations.
      RVAGE comprised 28.5% of all AGE hospitalizations. It was found that the annual
      RVAGE-related hospitalization incidence was 629/100,000 in those aged < 1 year,
      553/100,000 in those aged < 2 years, 293/100,000 in those aged < 5 years, and
      17/100,000 in those aged 5-14 years. Rotavirus acute gastroenteritis (RVAGE) in
      both hospitalized and outpatient cases was found to be higher (60%) in boys than
      girls. It was found that the RV positivity in hospitalized AGE cases was higher
      than in outpatient AGE cases (28.5% vs. 21%, p = 0.002). Eighty-six percent of
      hospitalized and 76% of outpatient RVAGE cases were < 5 years (p = 0.018). When
      the monthly distribution of RVAGE was examined in hospitalized and outpatient
      cases, it was found that RVAGE increased rapidly after October and decreased
      after March in cases aged < 5 years. The highest RV positivity rate was detected
      as 49.5% in January in hospitalized AGE cases and 31.5% in February for
      outpatient cases. In those < 5 years, the lowest RV positivity rate was detected
      in the June-September period both in hospitalized (between 11-25%) and in
      outpatient (between 0-18%) cases. Nearly half (47%) of the hospitalized RVAGE in
      those < 5 years were hospitalized in the January-March period. More than half of
      the outpatient RVAGE cases (55%) aged < 5 years were detected in the January
      March period. No meaningful differences were found in the monthly distribution
      and in the monthly RV positivity rates between hospitalized and outpatient cases.
      In conclusion, RV was found to be a significant etiologic agent in hospitalize
      (28.5%) and outpatient (21%) AGE cases in Bursa. Nearly 80% of the RVAGE cases
      were aged < 5 years. Approximately half of the cases were seen in the January
      March period. In January, half of the hospitalized cases and one-third of the
      outpatient AGE cases were RVAGE. Our findings have revealed a comparable pattern
      in RVAGE epidemiology in Bursa to that of the European countries and the United
      States.

PMID- 22389983
TI  - Chickenpox complications, incidence and financial burden in previously healthy
      children and those with an underlying disease in Ankara in the pre-vaccination
      period.
AB  - The aim of this study was to determine the complications, financial burden and
      mortality caused by chickenpox using the data of Ankara, Turkey in the pre
      vaccination period. The study was conducted as a retrospective sectional study.
      Of the 65 patients admitted to our hospital, 34 (52.3%) had been previously
      healthy, 10 (15.4%) had previous chronic disease and 21 (32.3%) were
      immunocompromised. The most common complications of chickenpox in those patient
      groups were skin and soft tissue infections (41.2%), hematological complications
      (50%) and gastrointestinal complications (38.1%), respectively. We found
      10.6/100,000 and 8.7/100,000 rates of hospitalization due to chickenpox in Ankara
      for all children and for previously healthy children, respectively. The
      chickenpox-related mortality rate for the 0-17 age group was 3.03/1,000,000 in
      Ankara. In conclusion, we feel that a national vaccination program for chickenpox
      will lead to a significant decrease in the overall cost to our country.

PMID- 22389984
TI  - Profile of dengue patients admitted to a tertiary care hospital in Mumbai.
AB  - Dengue is a mosquito-borne arboviral infection that has become a public health
      concern in India and particularly Mumbai, where endemicity is on the rise. Fifty
      seven children having dengue infection admitted over 12 months (2008) in a child
      health unit of a teaching hospital in Mumbai and who were positive for IgM
      antibodies by ELISA test were retrospectively studied for clinical profile and
      outcome. Common clinical findings were fever (100%), hepatomegaly (66.6%),
      vomiting (40.3%), and significant bleeding manifestations (38.5%). Common
      laboratory findings were thrombocytopenia (platelet < 100,000/mm3 in 96.5%
      patients), increased liver enzymes (59.6%), hypoalbuminemia (50.8%), hyponatremia
      (40.3%), and deranged prothrombin time/partial thromboplastin time (PT/PTT)
      (33.3%). Third spacing in the form of ascites and pleural effusion was present in
      15.7% and 31.5% of patients, respectively. There was no correlation between
      platelet count and bleeding manifestation. Patients with dengue shock syndrome
      required more supportive therapy with blood products and inotropes and had a
      longer recovery time. Mortality in the study was 3.5%. PT/PTT, serum sodium,
      albumin, and white blood cell (WBC) counts were predictors of severity of dengue.
      To summarize, fever, hemorrhagic manifestations, hepatomegaly, thrombocytopenia,
      and evidence of plasma leakage (hemoconcentration, pleural effusion, ascites or
      hypoproteinemia) should lead a clinician to suspect dengue infection.

PMID- 22389985
TI  - Helicobacter pylori infection and peptic ulcer in eastern Turkish children: is it
      more common than known?
AB  - Helicobacter pylori (H. pylori) infection is mainly acquired in childhood and is
      frequent in developing countries. The infection is associated with chronic
      gastritis in all infected children, but peptic ulcer disease develops in a small
      number of them. In our country, H. pylori infection and associated peptic ulcer
      disease are common. In eastern Turkey, we found peptic ulcer disease in 13.2% of
      children who underwent endoscopic examination. Peptic ulcers were mostly gastric
      ulcers and H. pylori-positive in the studied population, and most of the children
      were admitted due to abdominal pain. As there are no well-established criteria
      leading directly to diagnosis, pediatricians should include H. pylori infection
      and peptic ulcer disease in the differential diagnosis list when evaluating
      children with abdominal pain, failure to thrive and upper gastrointestinal system
      bleeding.

PMID- 22389986
TI  - Assessment of bone density in children with cerebral palsy by areal bone mineral
      density measurement.
AB  - The aim of this cross-sectional study was to investigate the frequency of
      decreased areal bone mineral density (aBMD) among patients with cerebral palsy
      (CP), as estimated by using various aBMD Z-score adjustment methods. In addition,
      this study examined factors related to decreased aBMD scores. One hundred and two
      children between the ages of 3.2 and 17.8 years were examined. In patients with
      severe CP, the incidences of decreased aBMD according to various adjusting
      methods based on decimal age, bone age, height age, and height-for-age Z-score
      (HAZ) were 79.5%, 69.5%, 51.9%, and 38.3%, respectively. Abnormal levels of
      calcium, phosphorus, alkaline phosphatase, parathyroid hormone, or anticonvulsant
      were not predictive for a decreased aBMD. Mean aBMD Z-scores were significantly
      lower in all aBMD Z-score adjustment methods in patients with severe CP compared
      to patients with mild-to-moderate CP, except for the adjustment method based on
      HAZ.

PMID- 22389987
TI  - Transforming growth factor-beta1 (509 C/T, 915 G/C, 869 T/C) polymorphisms are
      not related to obesity in Turkish children.
AB  - Increasing expression of transforming growth factor-beta 1 (TGF-beta1) from fatty
      tissue affects the serum level and hence may stimulate expression of the other
      cytokines. The studies concerning the relation between TGF-beta1 polymorphisms
      and obesity have been performed in adults, and diverse results have been
      reported. In this study, we aimed to investigate the association of TGF-beta1 509
      C/T, 915 G/C, 869 T/C polymorphisms in childhood obesity and related pathologies.
      Two hundred and seventy-one children and adolescents were included in the study.
      One hundred and twenty-one of these cases were in the Obese Group and 150 were in
      the Control Group. In the Obesity Group, we searched the carbohydrate and lipid
      metabolism disorders such as insulin resistance, dyslipidemia and
      hepatosteatosis. The results of this study revealed the lack of an association
      between TGF-beta1 509 C/T, 915 G/C and 869 T/C polymorphisms and obesity. There
      were no relations between the polymorphism genotypes and obesity-related
      metabolic disturbances.

PMID- 22389988
TI  - Emergency room management of acute bronchiolitis: a randomized trial of nebulized
      epinephrine.
AB  - Acute bronchiolitis is a common, potentially life-threatening condition with few
      therapeutic options. In the present randomized study, we compared the clinical
      efficacies of nebulized epinephrine and salbutamol in the emergency room
      management of acute bronchiolitis. Primary outcome measures were improvement in
      mean respiratory rate, mean oxygen saturation value and severity score. Secondary
      outcome measures were length of hospital stay, hospitalization and relapse rates.
      A total of 75 patients were analyzed (36 epinephrine, 39 salbutamol). Both groups
      experienced a similar pattern of clinical improvement. Hospitalization rates were
      8.3% for epinephrine and 5.1% for salbutamol (p > 0.05), whereas relapse rates
      were 80% for epinephrine and 20% for salbutamol groups (p < 0.001). Respiratory
      syncytial virus was the most common virus identified (41%). We did not find a
      difference between salbutamol and epinephrine in terms of clinical improvement,
      but salbutamol can be a drug of choice due to its lower relapse and
      hospitalization rates compared to epinephrine.

PMID- 22389989
TI  - One-year follow-up of penis and testis sizes of healthy Turkish male newborns.
AB  - Penile length, penile diameter and testicular volume at birth reflect the
      activity and normality of the hypothalamus-pituitary-testicular axis. In this
      prospective longitudinal study, we aimed to measure penis and testicular size in
      healthy newborns at birth and 6 and 12 months of age. Seven hundred forty-six
      term healthy male newborns were enrolled in the study. According to measurements
      taken within 48 hours after birth, mean penile length (MPL) was 2.81 +/- 0.32 cm,
      mean penile diameter (MPD) 1.04 +/- 0.09 cm, right testicular volume (TV) 1.73 +/
      0.45 ml, and left TV 1.64 +/- 0.48 ml. At 6 months of age, MPL was 3.67 +/- 0.35
      cm, MPD 1.23 +/- 0.08 cm, right TV 2.07 +/- 0.31 ml, and left TV 2.00 +/- 0.27
      ml. At 12 months of age, MPL was 4.47 +/- 0.43 cm, MPD 1.25 +/- 0.09 cm, right TV
      2.01 +/- 0.12 ml, and left TV 2.01 +/- 0.13 ml. There was a weak albeit
      statistically significant correlation between weight, length and PL at birth. In
      conclusion, the MPL of newborns was shorter than that reported in the published
      data from other populations. This situation may be related to ethnicity in
      addition to the lower birth weight and length of our subjects when compared to
      the newborns in other populations. We observed a significant increase, more
      marked during the first six months, in MPL, MPD and TV, which can be explained by
      the hormonal mechanism during minipuberty.

PMID- 22389990
TI  - Frequency and correlates of psychiatric disorders in early childhood: a study of
      population and clinical samples in Turkey.
AB  - Behavioral and emotional problems experienced in early childhood may have a major
      impact on the development and functioning of a child, leading to a number of
      psychiatric problems at a later age. The purpose of this study was to determine
      the incidence of psychiatric disorders in 3-5-year-old children presenting to the
      Outpatients Department and in the general population, and the relationship
      between psychiatric disorders and the sociodemographic characteristics of the
      children. This was a cross-sectional study carried out in Kocaeli, Turkey. Data
      were collected from two different groups, one representing the general population
      and the other based on children presenting to the Pediatric Psychiatry
      Outpatients Department at Kocaeli University Faculty of Medicine. Of the 309
      children in the study, 187 (60.5%) were boys and 122 (39.5%) were girls. Children
      aged 3-5 years (n = 81) were assessed by clinical examination. The mean age of
      the children was 3.94 +/- 0.81 years. No significant difference was observed
      between the groups in terms of parents' age groups, presence of consanguineous
      marriage, family structure, and siblings. The mothers were assessed in terms of
      regular visits to their physicians, major medical conditions, medication use,
      alcohol or tobacco consumption, and stress factors during their pregnancies. No
      significant difference was found between the study samples. The presence of a
      medical problem after birth was significantly more common in the clinical sample.
      Of the children in the clinical sample, 79% had at least one psychiatric problem,
      while the ratio for the general population sample was 41.7%.

PMID- 22389991
TI  - Epstein-Barr virus encephalitis: findings of MRI, MRS, diffusion and perfusion.
AB  - Epstein-Barr virus is an infection that is known as infectious mononucleosis.
      Even though the central nervous system is not a primary region of involvement of
      this disease, neurological complications are reported rarely. In this case
      report, we evaluated a 15-month-old male who presented to the pediatric neurology
      clinic due to high fever and a neurologic attack. His serological tests and
      radiological examinations (magnetic resonance imaging (MRI), MR spectroscopy
      (MRS), diffusion-weighted imaging (DWI) and MR perfusion) were consistent with
      Epstein-Barr virus encephalitis, which is a very rare complication of infectious
      mononucleosis. Additionally, we discuss the MRI, MRS, DWI and MR perfusion
      findings of our case, which were different from other cases reported in the
      literature.

PMID- 22389992
TI  - Subglottic cysts in a patient with recurrent stridor and respiratory distress.
AB  - Subglottic cysts are rare causes of stridor in infancy and should be suspected in
      the case of intubation. A 15-month-old male presented with recurrent stridor and
      respiratory distress. Prematurity and intubation were present in his history. Two
      subglottic cysts below the glottis were diagnosed. The cysts were ruptured by
      flexible bronchoscopy. The child's stridor and other symptoms disappeared
      thereafter. Early diagnosis of subglottic cysts is important since the
      obstruction can be relieved by rupturing the cysts with bronchoscope, whereas
      development of a fibrotic stenosis may require a tracheotomy, with its attending
      morbidity.

PMID- 22389993
TI  - Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children.
AB  - . LEOPARD syndrome 2 (LS-2) (OMIM #611554) is a rare, dominantly inherited
      genetic disorder affecting multiple organ systems. We report two unrelated
      females of different ages whose phenotype fits best in the category of LEOPARD
      syndrome, both with proven mutations in the RAF1 gene not previouslyreported in
      pediatric patients. In our 10-year-old patient, who was negative in the PTPN11
      gene analysis but involving the RAF1 gene in a complementary analysis, the
      sequence variant Ser257Leu (770C > T, exon 7) was detected, which previously had
      been reported in only one 35-year-old woman with LS. The second patient was a two
      year-old female infant with Ser259Leu mutation in the same gene, described in
      several patients with Noonan syndrome (NS) but not in LS patients of any age. The
      first girl had ventricular and supraventricular extrasystoles, and the second had
      episodes of paroxysmal supraventricular tachycardia. Echocardiographic
      examination revealed biventricular obstructive hypertrophic cardiomyopathy in
      both patients.

PMID- 22389994
TI  - Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed
      diagnosis with pseudodendritic corneal lesion.
AB  - Richner-Hanhart syndrome (tyrosinemia type II) is a rare autosomal recessive
      disease associated with high serum tyrosine levels caused by the deficiency of
      tyrosine aminotransferase enzyme. We report a 15-year-old female patient with
      complaints of bilateral photophobia and tearing, which started during the infancy
      period. Biomicroscopic examination revealed bilateral circular corneal opacities
      on the inferior quadrant and small dendritic lesions at the center of the
      circular opacities. Blood tests showed a tyrosine level of 508 micromol/L (normal
      range: 30-150). On her dermatologic examination, plantar hyperkeratosis and
      seborrheic dermatitis were noted, and mild mental retardation was detected. One
      and a half months after the tyrosine- and phenylalanine-restricted diet, her
      tyrosine level dropped to 395 micromol/L level, her corneal lesions subsided, and
      a symptomatic relief was achieved. Tyrosinemia type II should be suspected in
      patients demonstrating dermatologic signs, especially palmoplantar keratosis,
      associated with bilateral pseudodendritic corneal lesions unresponsive to
      antiviral therapy.

PMID- 22389995
TI  - Challenges of radiological assessment in an infant with giant calcified
      hepatoblastoma.
AB  - Hepatoblastoma is a rare neoplasm of all pediatric cancers. The goal of treatment
      is to remove the tumor completely because cure without complete resection is
      extremely unusual. Accurate assessment of tumor resectability following
      preoperative chemotherapy is of crucial importance. It is sometimes difficult,
      especially when the tumor is as large and calcified as in the described case.
      Detailed radiological imaging such as computed tomography angiography or magnetic
      resonance angiography is the key for selecting the proper treatment method in
      hepatoblastoma during the preoperative period. In this article, we report a
      successfully treated giant calcified hepatoblastoma despite radiological
      assessment complexity.

PMID- 22389996
TI  - A 1.5 cm-long unknown subconjunctival grass inflorescence misdiagnosed as
      relapsing conjunctivitis for one year.
AB  - Foreign bodies are usually detected at the first visit. However, they may be
      overlooked sometimes, especially in children, and may cause some clinical
      conditions including unilateral relapsing conjunctivitis. A five-year-old girl
      was presented to the emergency clinic of our hospital with epiphora, purulent
      discharge, eyelid swelling, and a foreign body feeling in her right eye. The
      symptoms had been present for one year, and the patient was treated for relapsing
      conjunctivitis. In slit lamp examination performed with difficulty because of the
      patient's lack of cooperation, a localized edema and erythema were observed under
      the right eyelid. An exploration under general anesthesia was planned, and a 1.5
      cm-long subconjunctival grass inflorescence was removed. An unknown
      subconjunctival foreign body should be considered in each patient with relapsing
      conjunctivitis, especially in children, even in the absence of ocular trauma.

PMID- 22389998
TI  - Neonatal gastrointestinal mucormycosis in an asphyxiated premature newborn.
AB  - Mucormycosis of the intestine is a rare fungal infection of childhood and is
      mostly encountered in neonates. It is a potentially lethal opportunistic fungal
      infection with rapid progression and high mortality in immunocompromised
      patients. The number of reported cases with intestinal mucormycosis is 19 to
      date. We herein report an asphyxiated preterm infant with intestinal mucormycosis
      who was presented with an atypical necrotizing enterocolitis (NEC), with findings
      similar to an intraabdominal mass. The diagnosis was made in the postmortem
      examination of the surgically removed bowel segment. Prematurity and asphyxia are
      important risk factors for mucormycosis. We suggest that the diagnosis of
      gastrointestinal mucormycosis should be considered in the differential diagnosis
      of atypical NEC cases.

PMID- 22389997
TI  - Hypopituitarism masquerading as Prasad's syndrome: a case report.
AB  - Prasad's syndrome is characterized by geophagia, growth retardation,
      hypogonadism, and zinc deficiency. We report a 15-year-old boy whose medical
      history and clinical and laboratory findings were fully compatible with Prasad's
      syndrome. In addition to severe growth retardation and pubertal delay, iron
      deficiency anemia and zinc deficiency were determined. His gliadin and endomysium
      antibodies were negative. The thyroid hormone levels were in normal range but
      basal gonadotropins and testosterone levels were low for his age. Detailed
      endocrinological evaluation revealed growth hormone deficiency and
      hypogonadotropic hypogonadism. Pituitary gland magnetic resonance imaging
      revealed pituitary hypoplasia. In our opinion, before the diagnosis of Prasad's
      syndrome, endocrine evaluation should be done in these patients and
      hypopituitarism should be ruled out. Hypogonadotropic hypogonadism and growth
      hormone deficiency may be masked by Prasad's syndrome.

PMID- 22389999
TI  - Albendazole-induced dystonic reaction: a case report.
AB  - Drug-induced dystonic reactions are a common presentation to the emergency
      department and typically occur with drugs like chlorpromazine, haloperidol and
      metoclopramide. There are no reports in the literature of dystonic reaction
      caused by albendazole. We report a case of albendazole-induced acute dystonic
      reaction whose symptoms completely resolved after the discontinuation of the
      drug. Even though dystonia side effects of albendazole are rare, it can induce an
      alarming dystonia in some sensitive children. The mechanism of dystonia is
      unclear.

PMID- 22390000
TI  - Proximal humeral physeal widening: little leaguer's shoulder or a variation of
      normal development?
AB  - Little leaguer's shoulder is a syndrome involving the proximal humeral epiphyseal
      plate and has been reported in adolescent athletes between 13-16 years of age. We
      present an adolescent case with radiological findings of little leaguer's
      shoulder syndrome in a non-athletic patient. The patient had applied significant
      rotational stress to the proximal humeral physis as a result of overuse due to
      physiotherapy, but the left asymptomatic side appeared more affected
      radiologically, which led to the idea that this may be a physiological change
      that occurs in adolescents. We thus evaluated the anteroposterior radiography of
      10 healthy male adolescents of the same age with no skeletal or muscular
      complaints. We demonstrated a minimal widening of the lateral part of the
      proximal humeral epiphysis in two of these 10 patients. We believe little
      leaguer's shoulder should also be considered in adolescents with proximal humeral
      pain and a history of overuse. A larger study must be conducted to investigate
      whether these finding may be a variation of physiological development.

PMID- 22390001
TI  - Acute motor axonal neuropathy and H1N1 influenza A infection.

PMID- 22390002
TI  - About selective IgA deficiency.

PMID- 22390003
TI  - Vitamin B12 (vit B12) deficiency treatment in infants and its prevention.

PMID- 22390004
TI  - Reaching out to the world: Dr. Lamb to receive 2012 Humanitarian Award from ADA.

PMID- 22390005
TI  - Confirmation overload--how much is too much?

PMID- 22390006
TI  - Staff bonuses vs. benefits.

PMID- 22390007
TI  - Climate change: evidence or opinion.

PMID- 22390009
TI  - Kindness, caring and compassion.

PMID- 22390008
TI  - No to cutbacks on conditions.

PMID- 22390010
TI  - Working rural and remote: rewards and challenges.

PMID- 22390011
TI  - Care of the post percutaneous coronary intervention patient.

PMID- 22390012
TI  - Industrial action and patient safety ethics.

PMID- 22390013
TI  - Universal antenatal chlamydia screening by rural midwives.

PMID- 22390014
TI  - Early recognition and response to clinical deterioration: the COMPASS journey.

PMID- 22390015
TI  - Clinical competence of nursing students.

PMID- 22390016
TI  - Fostering nursing research.

PMID- 22390017
TI  - Falls e-learning program.

PMID- 22390018
TI  - Breaking tradition.